PMID- 7500348
TI  - Complex salt bridges in proteins: statistical analysis of structure and function.
AB  - We developed an algorithm to analyze the distribution and geometry of simple and
      complex salt bridges in 94 proteins selected from the Protein Data Bank. In this
      study, the term "salt bridging" denotes both non-bonded and hydrogen-bonded
      paired electrostatic interactions between acidic carboxyl groups and basic amino
      groups in single or adjacent protein chains. We defined complex salt bridges as
      those joining more than two charged residues, including Asp, Glu, Lys and Arg,
      and excluding His. The survey related the following special features of complex
      salt bridges. (1) The abundance of complex salt bridges is high; one-third of all
      residues participating in salt-bridge formation were part of complex salt
      bridges. (2) The geometry of the interaction between acidic and basic residues is
      very similar in simple and complex salt bridges. Adding one residue to a simple
      interaction represents a minor change in the geometry but provides the molecule
      with a more complex interaction, a phenomenon that may explain the cooperative
      effect of salt bridges in proteins. Such moderate changes in salt-bridge networks
      can be generated stepwise and reversibly without trapping the protein in a local
      energetic minimum. (3) One important role of complex salt bridges is connecting
      protein subunits or joining two secondary structures to form quaternary
      structures, where they can connect as many as five secondary structure units. (4)
      Arginine serves as a key connector and/or a branching unit because its geometry
      allows three possible directions of interactions. The information gained from
      this study of complex salt bridges should enhance the understanding of protein
      structure.

PMID- 7500349
TI  - Molecular dynamics simulation of E. coli ribonuclease H1 in solution: correlation
      with NMR and X-ray data and insights into biological function.
AB  - A 500 ps molecular dynamics simulation of Escherichia coli RNase H1 in the
      presence of explicit water molecules has been carried out to aid in the
      interpretation of NMR N-H backbone model free parameters and X-ray B-factor
      values of the free enzyme. Both experimental techniques have revealed unusual
      structural and dynamic features of the protein. Atomic fluctuations (B-factors)
      and re-orientational motions of the backbone heteronuclear bonds (order
      parameters) computed from the simulation are compared with results obtained from
      experiments. Qualitative agreement is obtained between the computed and X-ray B
      factors, whereas the agreement between the computed and NMR generalized order
      parameters is as good as quantitative for most residues. Reasons for significant
      discrepancies, the physical basis and the plausible biological consequences of
      the observed protein dynamics are discussed.

PMID- 7500350
TI  - In vitro binding of ciliary neurotrophic factor to its receptors: evidence for
      the formation of an IL-6-type hexameric complex.
AB  - Ciliary neurotrophic factor (CNTF) is a cytokine sharing structural and
      functional similarities with interleukin-6 (IL-6) and other helical cytokines
      that utilize the common signalling chain gp130. While IL-6 induces gp130
      dimerization, CNTF, after the initial interaction with the specific, non
      signalling receptor subunit, CNTFR, induces the formation of gp130/LIF-receptor
      heterodimers. Through immunoprecipitation experiments with tagged soluble
      receptor molecules, we recently demonstrated that IL-6 drives the formation of a
      hexameric receptor complex with a defined topology and composed of two IL-6, two
      IL-6R alpha and two gp130 molecules. Here, we apply the same strategy to study
      the assembly in vitro of the CNTF receptor complex. We present evidence that both
      the cytokine and the specific binding chain undergo dimerization in the presence
      of gp130. Furthermore, although gp130 and LIFR are able to bind independently to
      the CNTF/CNTFR sub-complex, they never form homodimers but only heterodimers. We
      propose that CNTF assembles a hexameric receptor complex composed of two CNTF,
      two CNTFR, one gp130 and one LIFR molecule, and present a model of the reciprocal
      interaction of these molecules based on similarities with the IL-6 hexameric
      complex.

PMID- 7500351
TI  - The meaning of component analysis: decomposition of the free energy in terms of
      specific interactions.
AB  - Free energy simulations are of particular interest for the interpretation of
      macroscopic data in terms of microscopic interactions. This can be done by
      expressing calculated free energies as a sum of components that correspond to the
      contributions of different energy terms or different parts of the system. Since
      the resulting components depend on the integration path, care is required for
      their use. We show that a linear coupling scheme for the alchemical creation of a
      chemical identity corresponds to a particularly useful path because it leads to a
      symmetric decoupling of the free energy components. The path dependence also
      provides an additional degree of freedom that can be used to study different
      processes. This latter point is illustrated by a reinterpretation of a recent
      simulation on wild-type and mutant azurin by Mark and van Gunsteren.

PMID- 7500352
TI  - Kinetics of RNA polymerase initiation and pausing at the lambda late gene
      promoter in vivo.
AB  - We have measured the kinetics of transcription initiation and pausing by
      Escherichia coli RNA polymerase (RNAP) at the bacteriophage lambda late promoter,
      pR's, in growing cells. RNAP initiating transcription from pR' pauses after
      transcribing 16 or 17 nucleotides, and escape from this pause could in theory be
      the rate-limiting step in promoter function. We tested this hypothesis by
      analyzing pausing and non-pausing variants of both the pR' promoter segment and a
      more active mutant version of pR'; we measured reporter gene expression and used
      KMnO4 footprinting to measure directly occupancy of the promoter and pause sites
      in growing cells. We find that RNAP paused at +16/+17 does not limit expression
      of pR'. However, RNAP paused at +16/+17 does limit expression from the more
      active promoter by impeding formation of open complex. Therefore, the activity of
      the late gene regulatory protein Q to suppress the early pause, in addition to
      its antitermination activity, is unlikely to be important in phage gene
      expression.

PMID- 7500353
TI  - Structural and functional dissections of transcription termination factor rho by
      random mutagenesis.
AB  - Transcription termination factor rho from Escherichia coli is a homohexamer of
      419 amino acid subunits and catalyzes an ATP-dependent release of nascent RNA
      transcripts. A rho monomer has three distinct domains functioning independently
      at the first approximation: the amino-terminal one quarter containing a primary
      RNA-binding site, the central 270-amino acids region constituting an ATP-binding
      domain with homologies to F1-ATPase, and the carboxy-terminal remainder with
      unknown function(s). To further delineate the structural and functional
      organizations of rho protein, we undertook its random mutagenesis using error
      prone polymerase chain reactions with the carboxy-terminal 100-amino acid region
      chosen as the initial target. From 14 mutants identified, rho protein was
      purified and characterized in vitro. Of these, 11 mutants are defective in
      termination in vivo and show decreased activities in various partial functions
      examined: ATP binding; RNA binding; and ATPase activities dependent on three
      cofactors with decreasing efficacies, poly(C), lambda cro RNA and poly(U). A few
      of them are also affected in the putative secondary RNA-binding site that is
      functionally coupled to ATP hydrolysis. By contrast, the three other mutants are
      hyperactive in termination, poly(U)-dependent ATPase activity, and RNA
      interaction at the primary site. In these properties, the hyper-terminating
      mutants strikingly resemble the "super rho" mutant formerly found in the amino
      terminal domain. Taken together, these findings indicate that the carboxy
      terminal region plays a pivotal role in functionally coupling the RNA and ATP
      binding domains, plausibly by acting as an interface for their interaction within
      or across individual subunits. In light of the reported X-ray crystallographic
      structure of F1-ATPase, we propose a model for the tertiary and quaternary
      structure of rho that is consistent with the observed mutational effects as well
      as a number of structural and functional properties characteristic of rho.

PMID- 7500354
TI  - The involvement of two distinct regions of 23 S ribosomal RNA in tRNA selection.
AB  - The role of ribosomal RNA in maintaining the accuracy of translation has been
      investigated genetically by selecting for rRNA mutations that promoted
      frameshifting at a specific site in a reporter gene in Escherichia coli.
      Mutations were recovered in two different regions of 23 S rRNA and each promoted
      readthrough of stop codons as well as increasing the levels of frameshifting. The
      first group of mutations was in a small stem loop (the 1916 loop) in domain IV of
      23 S rRNA. This stem-loop has been mapped to the subunit interface of the
      ribosome, close to the decoding center on the 30 S subunit. The second group of
      mutations was in helix 89, one of the helices emerging from the central loop of
      domain V. Helix 89 has been implicated in subunit-subunit interactions and
      peptidyltransferase activity, and it is proposed that mutations in helix 89
      influence the accuracy of decoding by affecting the interaction of the CCA end of
      the tRNA with the peptidyltransferase center.

PMID- 7500355
TI  - The action of pokeweed antiviral protein and ricin A-chain on mutants in the
      alpha-sarcin loop of Escherichia coli 23S ribosomal RNA.
AB  - The alpha-sarcin loop of Escherichia coli 23S rRNA is a universally-conserved
      structure involved in the binding of elongation factors Tu and G and is the site
      of action of the ribosome-inactivating proteins (RIPs). One such group, the N
      glycosidase RIPs, act by the removal of a single adenine residue (A2660) believed
      to exist in a GAGA-containing tetraloop structure. The action of two RIPs, the
      catalytic A-chain from the heterodimeric toxic lectin ricin (RTA) and the single
      chain RIP pokeweed antiviral protein (PAP), which are known to be highly
      homologous in tertiary structure, was determined on native ribosomes or naked 23S
      rRNA containing mutations designed to affect the structure of the GAGA tetraloop.
      One such mutant rRNA containing G2663C, which abolishes the potential tetraloop
      by disrupting the Watson-Crick base-pair involved in closing it, resulted in a
      loss of depurination by RTA, but not by PAP. A similar result was observed for
      mutant G2661A. The double mutant C2658G + G2663C, which restores the tetraloop
      closing base-pair but in the reverse orientation, resulted in sensitivity to both
      PAP and RTA, as in the wild-type. Thus, the tetraloop structure is required for
      the action of RTA, but not of PAP, and unlike RTA, PAP does not require G at
      position 2661. RNA containing the G2664C mutation, which lies outside the
      tetraloop, served as a substrate for both PAP and RTA. The comparison of the
      recognition elements for PAP and RTA was made with naked (deproteinised) rRNA,
      because RTA does not act on E. coli ribosomes. However, PAP is active on E. coli
      ribosomes, and it was found that the action of PAP on ribosomes containing the
      above mutations paralleled exactly that on the corresponding naked rRNAs. It is
      concluded that the recognition elements for PAP and RTA differ and may account,
      at least in part, for the fact that PAP but not RTA catalyses the depurination of
      E. coli ribosomes.

PMID- 7500356
TI  - Modelling viral evolution in vitro using exo- Klenow polymerase: continuous
      selection of strand displacement amplified DNA that binds an oligodeoxynucleotide
      to form a triple-helix.
AB  - Evolution comprises cycles of amplification, mutagenesis and selection. To study
      evolutionary phenomena, isothermal strand displacement amplification (SDA) of
      double-stranded DNA as an in vitro model for rolling-circle replication of
      viruses has been coupled to a positive selection procedure. First, two subsequent
      amplification reactions utilizing exo- Klenow polymerase were performed under
      direct observation using the fluorescent dye thiazole orange. Under the chosen
      conditions, the mutation rate was 1.5 x 10(-3) and 0.4 x 10(-3) for base
      substitutions and deletions, respectively. Then, a 16mer oligodeoxynucleotide
      with an acridine moiety coupled to its 5' end was used to select for double
      strands that retained their ability to form a triple-helix with the
      oligodeoxynucleotide. Conditions for triple-helix formation were chosen such that
      only 10 to 40% of the SDA products were allowed to bind the third strand. Non
      denaturing polyacrylamide gel electrophoresis was used to separate triple-helices
      from unmodified double strands, and only triplex strands were used to initiate a
      new round of error-prone amplification and selection. Nine such rounds with about
      270 molecular generations were performed. The final mutant spectrum was
      characterized and compared with those of amplification reactions without
      additional selection pressure. While without selection pressure base
      substitutions and deletions throughout the initial wild-type rapidly produce a
      diverse mutant distribution, the consensus after nine selection rounds clearly
      shows two mutational hotspot positions. Using gel shift assays and a newly
      developed non-radioactive DNase I footprinting technique, it could be shown that
      both the initial wild-type and the final consensus do not differ significantly in
      their triplex formation ability. As opposed to this, they do show different
      amplification efficiencies. The final consensus sequence is amplified with the
      highest rate in the exponential reaction phase, while the most abundant clone,
      which is characterized by two additional point deletions, is the sequence with
      the highest amplification rate in the linear growth phase.

PMID- 7500357
TI  - Targeted disruption of 01H1 encoding a particular H1 histone variant causes
      changes in protein patterns in the DT40 chicken B cell line.
AB  - Six members of the chicken H1 gene family, all of which are located in two major
      histone gene clusters, have been shown to encode six different protein variants.
      The intracellular mRNA level from one of them, 01H1, encoding the 01H1 variant
      composed of 218 amino acid residues, constitutes 9.9% of the total H1 mRNA in the
      DT40 chicken B cell line. To study the specific role of this particular H1
      variant, besides its well-known functions as a linker in chromatin maintenance
      and as a general repressor of transcription, we used targeted integration to
      construct heterozygous and homozygous DT40 mutants with disruption of one and two
      01H1 alleles, respectively. Analyses of the stable transfectants showed that the
      growth rate of DT40 was unchanged in the absence of two 01H1 alleles. Moreover,
      the remaining H1 genes were shown to be expressed more in these mutants than in
      the wild-type cell lines. Two-dimensional polyacrylamide gel electrophoresis
      showed that within an almost constant background in the homozygous mutants
      several cellular proteins newly appeared or increased, while some other proteins
      disappeared or decreased quantitatively. These variable proteins all differed
      from those that varied in DT40 mutants deprived of one of the eight chicken H2B
      genes, H2B-V, encoding a particular H2B variant. These results suggest that the
      01H1 variant is involved in the regulation of expression of genes that encode the
      proteins that vary in 01H1-deleted mutants of DT40 cells.

PMID- 7500358
TI  - The ribosomal DNA loci in Plasmodium falciparum accumulate mutations
      independently.
AB  - Homogeneity of rDNA sequence within a cell is maintained by mechanisms working at
      the DNA level. The imperative to maintain homogeneity is thought to result from
      pressure to maintain the sequence of the rRNA transcript. We have investigated
      the extent of sequence variation within and between members of a species that is
      unable to utilize some standard mechanisms of rDNA sequence correction. We have
      compared the sequence of the internal transcribed spacer (ITS1) located between
      the 18 S rRNA and 5.8 S rRNA genes of five different loci of a single Plasmodium
      falciparum genotype. The ITS1 sequences are identical at 80 to 91% of the
      positions among the three asexually expressed genes (A-types) and 75% between the
      two genes expressed during sporogony (S-types), with only 42 to 57% identity
      between the types. This is rather startling in that the differences described
      here for a single genome are greater than those normally seen when comparing rDNA
      units from distantly related organisms. We observe an apparent conservation of
      secondary structure within ITS1 sequences from the different transcription units,
      which would reflect a level of selection at the rRNA but the organism seems to be
      quite tolerant of primary sequence variation. Investigation of the mature coding
      region within the 18 S rRNA genes did not reveal sequence variation within A- and
      S-types from a single genotype. However, comparison of the 18 S rRNA coding
      region from 17 geographically distinct strains reveals up to 10% sequence
      variation within a 400 nucleotide region. Hence homogeneity of rRNA units within
      a species does not seem to be an imperative driven totally by selection at the
      RNA level. The extraordinary maintenance of homogeneity within rDNA units
      normally seen within a species appears to have significance beyond those that can
      be ascribed to the events involved in processing, assembly and function of the
      ribosome.

PMID- 7500359
TI  - Binding of mouse and human fibulin-2 to extracellular matrix ligands.
AB  - Recombinant mouse and human fibulin-2 were obtained as disulfide-bonded trimers
      from transfected kidney cell clones and used in solid phase, biosensor and
      radioligand binding assays. Strong binding occurred with fibronectin and required
      calcium. A distinct interaction was also observed with nidogen but this was only
      partially blocked by EDTA. Distinctly weaker affinities were detected for
      collagen IV, perlecan and the N-terminal globule of collagen VI alpha 3 chain,
      while no or only little binding activity could be detected for several other
      collagen types, laminin-1, BM-40, fibulin-1 and vitronectin. This weaker binding
      reactions were also dependent on calcium. Surface plasmon resonance assays
      demonstrated for fibulin-2 binding to nidogen and fibronectin high equilibrium
      dissociation constants (0.5 to 1 microM) due to a rapid initial dissociation of
      the complexes. This is apparently followed by a slower stabilizing reaction. The
      fibulin-2 binding site of nidogen could be localized to its C-terminal globular
      domain G3, which also possesses a high-affinity binding site for laminin-1.
      Several tests demonstrated competition between the two ligands, probably due to
      steric hindrance. Binding of nidogen to immobilized fibulin-2 allowed the
      formation of ternary complexes with collagen IV, perlecan and fibulin-1, which,
      as shown previously, bind independently of the G3 domain. This indicated
      multifunctional binding properties for fibulin-2 and several alternative routes
      for its integration into basement membranes and other extracellular structures.

PMID- 7500360
TI  - The binding of 2-deoxy-D-glucose 6-phosphate to glycogen phosphorylase b: kinetic
      and crystallographic studies.
AB  - Kinetic and crystallographic studies have characterized the effect of 2-deoxy
      glucose 6-phosphate on the catalytic and structural properties of glycogen
      phosphorylase b. Previous work on the binding of glucose 6-phosphate, a potent
      physiological inhibitor of the enzyme, to T state phosphorylase b in the crystal
      showed that the inhibitor binds at the allosteric site and induces substantial
      conformational changes that affect the subunit-subunit interface. The hydrogen
      bond from the O-2 hydroxyl of glucose 6-phosphate to the main-chain oxygen of
      Val40' represents the only hydrogen bond from the sugar to the other subunit, and
      this interaction appears important for promoting a more "tensed" structure than
      native T state phosphorylase b. 2-Deoxy-glucose 6-phosphate acts competitively
      with both the activator AMP and the substrate glucose 1-phosphate, with Ki values
      of 0.53 mM and 1.23 mM, respectively. The binding of 2-deoxy-glucose 6-phosphate
      to T state glycogen phosphorylase b in the crystal, has been investigated and the
      complex phosphorylase b: 2-deoxy-glucose 6-phosphate has been refined to give a
      crystallographic R factor of 17.3%, for data between 8 A and 2.3 A. 2-Deoxy
      glucose 6-phosphate binds at the allosteric site as the a anomer and adopts a
      different conformation compared to glucose 6-phosphate. The two conformations
      differ by 160 degrees in the torsion angle about the C-5-C-6 bond. The contacts
      from the phosphate group are essentially identical to those made by the phosphate
      of glucose 6-phosphate but the 2-deoxy glucosyl moiety binds in a quite different
      orientation compared to the glucosyl of glucose 6-phosphate. 2-Deoxy-glucose 6
      phosphate can be accommodated in the allosteric site with very little change in
      the protein, while structural comparisons show that the phosphorylase b: 2-deoxy
      glucose 6-phosphate complex structure is overall more similar to a glucose-like
      complex than to the Glc-6-P complex structure.

PMID- 7500361
TI  - The refined X-ray structure of muconate lactonizing enzyme from Pseudomonas
      putida PRS2000 at 1.85 A resolution.
AB  - We report here the refined X-ray crystal structure of muconate lactonizing enzyme
      (MLE) from Pseudomonas putida PRS2000 at a resolution of 1.85 A with an R-factor
      of 16.8%. An enzyme from the beta-ketoadipate pathway, MLE catalyses the
      conversion of cis,cis-muconate to muconolactone. It is a homo-octamer, one
      monomer consisting of 373 amino acid residues. MLE has two large domains and a C
      terminal subdomain: an alpha + beta domain, an alpha beta-barrel domain and a C
      terminal meandering subdomain. The alpha beta-barrel domain is highly irregular.
      Its structure is (beta/alpha)7 beta, with the structural role of the last alpha
      helix being replaced by both the C-terminal subdomain and part of the N-terminal
      domain. The fifth, seventh and eighth barrel strands are unusual because they
      have left-handed twist about their axes. The strand crossing angles also vary
      enormously, from +9 degrees to -69 degrees; the first and last strands, which
      close the barrel, cross at an angle of -69 degrees, making extensive strand
      strand hydrogen bonding impossible. The first barrel strand is also unusual
      because it starts in the N-terminal domain and forms hydrogen bonds to the C
      terminal subdomain beta-sheet as well as to its neighbouring strands in the
      barrel. It thus cements the whole protein together. As in other alpha beta-barrel
      proteins, the active site of MLE, present in each subunit is at the C-terminal
      ends of the barrel beta-strands. The active site cleft contains an essential
      manganese ion, is lined with charged and other polar residues, and contains many
      of the crystallographic water molecules. The manganese ion is octahedrally co
      ordinated to three side-chain carboxylate groups and three water molecules, and
      is at the centre of a radiating web of ionic and hydrogen-bonding interactions.
      Additionally, two water molecules are buried in the centre of the barrel and two
      hydrophilic side-chains (Lys167 and Arg196) make both hydrophobic and hydrophilic
      packing interactions with much of the barrel interior. The barrel interior is
      thus also unusual because it is so hydrophilic; the dominating force appears to
      be the need to solvate the metal ion effectively. This might account for the
      irregularity of the barrel. The catalytic mechanism has been investigated by
      docking both substrate and product in the active site with the C-COO- of
      muconolactone superimposed on the corresponding atoms of cis,cis-muconate. In
      agreement with earlier kinetic and spectroscopic results, the manganese ion does
      not interact directly with substrate or product.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7500362
TI  - Crystal structure of the catalytic subunit of human protein phosphatase 1 and its
      complex with tungstate.
AB  - Protein phosphatase 1 (PP1) is a serine/threonine protein phosphatase that is
      essential in regulating diverse cellular processes. Here we report the crystal
      structure of the catalytic subunit of human PP1 gamma 1 and its complex with
      tungstate at 2.5 A resolution. The anomalous scattering from tungstate was used
      in a multiple wavelength anomalous dispersion experiment to derive
      crystallographic phase information. The protein adopts a single domain with a
      novel fold, distinct from that of the protein tyrosine phosphatases. A di-nuclear
      ion centre consisting of Mn2+ and Fe2+ is situated at the catalytic site that
      binds the phosphate moiety of the substrate. Proton-induced X-ray emission
      spectroscopy was used to identify the nature of the ions bound to the enzyme. The
      structural data indicate that dephosphorylation is catalysed in a single step by
      a metal-activated water molecule. This contrasts with other phosphatases,
      including protein tyrosine phosphatases, acid and alkaline phosphatases which
      form phosphoryl-enzyme intermediates. The structure of PP1 provides insight into
      the molecular mechanism for substrate recognition, enzyme regulation and
      inhibition of this enzyme by toxins and tumour promoters and a basis for
      understanding the expanding family of related phosphatases which include PP2A and
      PP2B (calcineurin).

PMID- 7500363
TI  - Partially folded states of proteins: characterization by X-ray scattering.
AB  - Partially folded states of proteins are found to occur with a wide variety of
      degrees of unfolding, ranging from the compact molten globule to the fully
      unfolded forms, depending on solvent conditions and the specific protein
      involved. Small to intermediate angle X-ray scattering from partially folded
      states of proteins yields low resolution scattering profiles that may be used to
      explore the degree of folding of a protein under given solution conditions. By
      Monte Carlo simulation of a highly simplified homopolymer model, we show that
      such partially folded states will yield a characteristic scattering profile that
      may be written as a linear superposition of scattering from a compact core and of
      scattering from random coil loops that emerge from this core. We also find a term
      resulting from interference of X-rays scattering from the core with those
      scattering from the loops. This interference term oscillates in sign and tends to
      enhance the core portion of the scattering profile. We compare the model
      calculations of the scattering profile with measurements of the scattering
      profile as a function of salt concentration for cytochrome c at pH 2. Because of
      our characterization of the scattering profiles, we suggest that these results
      may be re-interpreted in terms of the presence of a range of partially folded
      states as a function of pH and salt concentration, and that the observed
      scattering profiles are consistent with the characterization of the partially
      folded states in terms of random coil loops emerging from a compact core with the
      loop fraction increasing as the salt concentration is decreased. This
      characterization is consistent with data on amide protection against H-2H
      exchange of compact regions within partially folded states observed for a number
      of proteins, including cytochrome c.

PMID- 7500364
TI  - Conformational pathway of the polypeptide chain of chymotrypsin inhibitor-2
      growing from its N terminus in vitro. Parallels with the protein folding pathway.
AB  - We have obtained a series of fragments growing from the N terminus of the protein
      chymotrypsin inhibitor-2 (C12) in order to study the development of structure on
      elongation of the polypeptide in solution. We present an extensive biophysical
      characterization of ten fragments using different conformational probes. Small
      fragments up to residue 40 of the 64-residue protein are disordered. Fragment (1
      40) has non-native local hydrophobic clusters, but nevertheless does not bind 8
      anilinonaphthalene-1-sulphonate (ANS). Hydrophobic regions in longer fragments
      become gradually more capable of binding ANS as the chain grows to completion,
      with a tendency to form native structures. Major changes in secondary structure
      and accessibility to hydrophobic sites occur in parallel, between (1-40) and (1
      53), together with changes in hydrodynamic volume and flexibility. NMR studies of
      (1-53), the first fragment displaying tertiary interactions, show that a subcore
      is fully formed and the alpha-helix (residues 12 to 24) is of fluctuating
      structure. Fragments (1-53) and (1-60) share many properties with molten globule
      like structures, with varying degrees or order. Fluorescence properties of the
      native fold are gradually recovered from fragments (1-60) to full-length C12,
      together with a decrease in hydrophobic exposure. A small degree of co
      operativity of formation of structure appears when residue 60 is added, gradually
      increasing as residue 62 is added, but a full two-state co-operative transition
      appears only on addition of Arg62 and Val63. We believe this is the result of
      correct side-chain packing of the hydrophobic core, capping the major elements of
      secondary structure in C12 at this late stage, which is probed by the complete
      recovery of the fluorescence of the unique Trp5. The structures that develop as
      the polypeptide chain increases in length parallel the structural features
      present in the nucleus for the folding of intact protein, which develops in the
      transition state. The folding nucleus consists of much of the helix and the
      interactions made by Ala16 in the helix with residues in the core, especially
      with Leu49 and Ile57, with the rest of the structure being formed only very
      weakly in the transition state.

PMID- 7500365
TI  - Perturbed pKA-values in the denatured states of proteins.
AB  - We show in this study that the ionisation equilibria of denatured proteins in
      pure water are inconsistent with the "fully-unfolded" conformation being an
      extended coil where the residues are isolated from one another by the intervening
      solvent. The effects of acid and salt on the stability of the barley chymotrypsin
      inhibitor 2 (CI2) were investigated and the pKA-values of all carboxylate
      residues in the native protein were determined by NMR. A comparison of the
      experimentally determined pH-dependence of the protein stability and that
      calculated using observed pKA-values in the native state, reveals that the pKA
      values in the denatured state are, on average, 0.3 pH units lower than those of
      model compounds. An increase in ionic strength eliminates these pKA shifts in the
      denatured state. This shows that there are electrostatic interactions in the
      denatured state of CI2. Since previous studies on barnase and the Ovomucoid Third
      Domain also report anomalous titration behaviours of the denatured states, it
      appears that perturbed pKA-values in the denatured state is a general phenomenon,
      indicating that the unfolded conformation in pure water is a fairly compact
      species. In addition, we used a mutational approach to determine the pKA-values
      of a carboxylate group in both the native and denatured states. The pKA-value in
      the native state obtained by this method is in precise agreement with that
      obtained by NMR.

PMID- 7500366
TI  - Steroid recognition by chloramphenicol acetyltransferase: engineering and
      structural analysis of a high affinity fusidic acid binding site.
AB  - The antibiotic fusidic acid and certain closely related steroidal compounds are
      potent competitive inhibitors of the type I variant of chloramphenicol
      acetyltransferase (CATI). In the absence of crystallographic data for CATI, the
      structural determinants of steroid binding were identified by (1) construction in
      vitro of genes encoding chimaeric enzymes containing segments of CATI and the
      related type III variant (CATIII) and (2) site-directed mutagenesis of the gene
      encoding CATIII, followed by kinetic characterisation of the substituted
      variants. Replacement of four residues of CATIII (Gln92, Asn146, Tyr168 and
      Ile172) by their equivalents from CATI yields an enzyme variant that is
      susceptible to competitive inhibition by fusidate with respect to chloramphenicol
      (Ki = 5.4 microM). The structure of the complex of fusidate and the
      Q92C/N146F/Y168F/I172V variant, determined at 2.2 A resolution by X-ray
      crystallography, reveals the inhibitor bound deep within the chloramphenicol
      binding site and in close proximity to the side-chain of His195, an essential
      catalytic residue. The aromatic side-chain of Phe146 provides a critical
      hydrophobic surface which interacts with non-polar substituents of the steroid.
      The remaining three substitutions act in concert both to maintain the appropriate
      orientation of Phe 146 and via additional interactions with the bound inhibitor.
      The substitution of Gln92 by Cys eliminates a critical hydrogen bond interaction
      which constrains a surface loop (residues 137 to 142) of wild-type CATIII which
      must move in order for fusidate to bind to the enzyme. Only two hydrogen bonds
      are observed in the CAT-fusidate complex, involving the 3-alpha-hydroxyl of the A
      ring and both hydroxyl of Tyr25 and NE2 of His195, both of which are also
      involved in hydrogen bonds with substrate in the CATIII-chloramphenicol complex.
      In the acetyl transfer reaction catalysed by CAT, NE2, of His195 serves as a
      general base in the abstraction of a proton from the 3-hydroxyl of
      chloramphenicol as the first chemical step in catalysis. The structure of the CAT
      inhibitor complex suggests that deprotonation of the 3-alpha-hydroxyl of bound
      fusidate by this mechanism could produce an oxyanion nucleophile analogous to
      that seen with chloramphenicol, but one which is incorrectly positioned to attack
      the thioester carbonyl of acetyl-CoA, accounting for the observed failure of CAT
      to acetylate fusidate.

PMID- 7500367
TI  - Sexual satisfaction among Korean-American couples in the Midwestern United
      States.
AB  - One hundred couples composed of American husbands and Korean wives from the
      midwestern United States were surveyed with respect to sexual satisfaction.
      Though the responses of spouses were correlated highly, husbands were more
      satisfied with the quality of the sexual relationship than were wives. As found
      previously with more general populations, self-esteem and higher levels of
      positive regard, communication, and cohesion were related to higher sexual
      satisfaction for both husbands and wives. For wives, higher socioeconomic status
      and younger age were related to higher sexual satisfaction, as was the husband's
      being a current or retired member of the US military. Cultural factors were also
      important; conflicts over sexual practices related to cultural differences,
      though limited to about 10% of the subjects, were related to sexual satisfaction
      for both husbands and wives. Wives' English proficiency was related slightly to
      sexual satisfaction, but not husbands' proficiency in Korean. For husbands only,
      marital conflict over cultural differences and rejection by relatives and friends
      were related negatively to sexual satisfaction. Clinical implications of the
      results are discussed.

PMID- 7500368
TI  - Low sexual desire in women: the effects of marital therapy.
AB  - A total of 49 couples, in which the women were experiencing inhibited sexual
      desire (ISD), received Emotionally Focused Therapy for Couples (EFT) or were
      assigned to a wait-list control group. An additional 15 couples were recruited as
      a non-ISD comparison sample. Only very modest treatment and control group
      differences were found after treatment. Females treated with marital therapy made
      significant gains on one measure of sexual desire and on level of depressive
      symptomatology. Overall, the marital treatment group seemed to make clinically
      significant gains from pre- to posttreatment which were largely maintained at
      follow-up. Lower levels of initial marital distress resulted in greater treatment
      gains, and better pretreatment marital adjustment predicted better posttreatment
      overall sexual adjustment. The main difference found between ISD and non-ISD
      couples was that ISD couples had significantly more sexual distress. Results are
      discussed in light of the unique features of this subject population, and
      suggestions are given for future research.

PMID- 7500369
TI  - On love.
AB  - This paper aims to stimulate awareness of the relationship between adult
      heterosexual love and sexual health. Although rarely discussed in professional
      circles, adult love is a powerful ideal that strongly influences both individual
      and relationship psychology. A gap between one's personal ideal of love and the
      actual experience of it inevitably appears within a long-term relationship. The
      feelings and behavior that stems from the gap become a crucial management issue
      for each individual in a relationship. The gap is minimized by an array of
      defenses and competing life demands, which either enhance or destabilize
      individual and relationship well-being. Idealization, denial, and rationalization
      are necessary to preserve the internal sense of loving at all phases of the
      committed relationship. The limitations of various definitions of sexual health
      are reviewed. Sixteen suggestions for preserving sexual health in long-term
      relationships are offered. Most of these involve guidelines for overcoming
      narcissism. The limitations of modern therapists, even sex therapists, for
      forthrightly dealing with sexual problems in terms of love are highlighted.

PMID- 7500370
TI  - Antidepressant-induced orgasm disorder.
AB  - Most of the antidepressants approved for use in the United States, with the
      possible exceptions of bupropion and nefazodone, have been associated with drug
      induced anorgasmia. Common strategies to overcome this drug side effect include
      waiting for tolerance to develop, dose reduction, change of dosing regimen,
      substitution of an alternative antidepressant, and coadministration of another
      drug. Current evidence suggests that antidepressant-induced anorgasmia may be
      mediated by 5HT2 antagonism of adrenergic mechanisms that underlie normal orgasm.

PMID- 7500371
TI  - Dating relationships and infidelity: attitudes and behaviors.
AB  - This study of 197 college student participants found that marital infidelity is
      significantly more unacceptable than dating infidelity. Men tended to be more
      lenient in their ratings of infidelity than women. Self-esteem scores were
      significantly higher for individuals who did not become involved in dating
      infidelity than for participants who did. However, self-esteem was not found to
      be a significant factor in whether a person remained in a current relationship in
      which the partner had been unfaithful.

PMID- 7500372
TI  - Factors predicting high-risk sexual behavior in heterosexual college females.
AB  - The purpose of this study was to determine which factors based in social
      cognitive theory are associated with risky sexual behavior in heterosexual
      college females. Results showed that negative attitudes toward condoms and toward
      involvement in a relationship were associated with less consistent condom use;
      frequent alcohol use preceding intercourse and low sexual satisfaction were
      associated with less consistent contraceptive use. Sex education on the college
      campus currently provides protection information only; these strategies have not
      proved successful. We encourage the development of more comprehensive educational
      strategies, which include discussion of the social cognitive factors shown here
      to be associated with risky sexual behavior.

PMID- 7500373
TI  - Exposure of tumor necrosis factor-alpha to luminal membrane of bovine brain
      capillary endothelial cells cocultured with astrocytes induces a delayed increase
      of permeability and cytoplasmic stress fiber formation of actin.
AB  - Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, has long
      been known to be involved in the pathogenesis of central nervous system
      infections and of certain neurodegenerative diseases. However, the possible role
      of the blood-brain barrier (BBB), the active interface between the blood
      circulation and brain tissue, remained unknown during these pathological
      conditions. In our in vitro reconstructed BBB model, 1-hr exposure of recombinant
      human TNF-alpha (in concentrations of 50, 250, and 500 U/ml, respectively) to the
      luminal membrane of bovine brain capillary endothelial cells (BBCEC) did not
      change significantly the transendothelial flux of either sucrose (m.w. 342 Da),
      or inulin (m.w. 5 kDa) up to 4 hr (early phase), except for a slight decrease (P
      < 0.05) in sucrose permeation at 2-4 hr with the highest dose of TNF-alpha. On
      the other hand, at 16 hr after the 1-hr challenge with TNF-alpha (delayed phase)
      at all 3 concentrations, significant increase was induced in the permeability of
      BBCEC monolayers for both markers. These changes of permeability were accompanied
      by a selective reorganization of F-actin filaments into stress fibers, while the
      intracellular distribution of vimentin remained similar to the control. These
      results suggest that BBCEC can respond directly to TNF-alpha by a delayed
      increase of permeability and reorganization of actin filaments.

PMID- 7500374
TI  - Hydrocortisone influences voltage-dependent L-type calcium channels in cultured
      human skeletal muscle.
AB  - The glucocorticoid hydrocortisone (HC), applied for up to 2 weeks to either
      aneurally or innervated cultured human muscle, produced 2-fold increase of the
      number of dihydropyridine ([3H]PN200-110) binding sites. The K(+)-induced,
      nifedipine-inhibited Ca2+ uptake was increased 40%. The effect of HC was
      concentration- and time-dependent. [3H]PN200-110 affinity for its receptor was
      not affected by HC treatment. HC did not exert significant influence on the total
      amount of protein, CK activity, and the number of myotubes. These results
      indicate that voltage-dependent L-type Ca2+ channel expression in human muscle is
      regulated by glucocorticoid.

PMID- 7500375
TI  - Identification of glial cell types involved in mediating epidermal growth
      factor's effects on septal cholinergic neurons.
AB  - We found previously that epidermal growth factor (EGF) decreases choline
      acetyltransferase (ChAT) activity in forebrain cholinergic neurons in vitro
      indirectly via glia (Kenigsberg et al.: Neuroscience 50: 85-97, 1992). However,
      which glial type(s) are implicated in this response remained to be determined.
      Here we report that in primary cultures from the fetal rat medial septal area the
      complete elimination of oligodendrocytes or partial elimination of microglia from
      these cultures does not change the cholinergic cell response to EGF. However, the
      elimination of astroglia in our cultures by alpha-aminoadipic acid treatment
      blocks EGF's effects on the cholinergic neurons. Co-culture experiments using
      pure neuronal and purified glial cells from the medial septum further demonstrate
      that the cholinergic cell response to EGF can be maintained in the presence of
      astroglia only. In addition, it appears that EGF regulates the release of soluble
      factors from pure astroglia cultures following their peak mitotic response to EGF
      that decreases ChAT enzymatic activity. This soluble cholinergic neuromodulatory
      activity found in conditioned media from EGF-treated astrocytes has a molecular
      weight greater than or equal to 10 kD and loses potency following multiple freeze
      thaw cycles. These results suggest that a direct glial cell response to a
      specific glial growth factor like EGF may have an important impact on the
      expression of local neurons, like the cholinergic in the forebrain.

PMID- 7500376
TI  - Reinnervation of a denervated slow muscle triggers high extrajunctional
      expression of the asymmetric molecular forms of acetylcholinesterase.
AB  - Expression of acetylcholine receptor and of the asymmetric molecular forms of
      acetylcholinesterase (AChE) in the extrajunctional regions of rat muscles is
      suppressed during early postnatal development. In mature muscles, the
      extrajunctional synthesis of acetylcholine receptor, but not of the asymmetric
      molecular forms of AChE, becomes reactivated after denervation. The hypothesis
      that a denervated muscle needs reinnervation in order to revert transiently to an
      immature state characterized by high extrajunctional production of the asymmetric
      AChE forms, was examined in rat muscles recovering after nerve crush. Molecular
      forms of AChE were analysed by velocity sedimentation. Activity of the asymmetric
      A12 AChE form in the extrajunctional regions of the slow soleus (SOL) muscle
      increased during the first week after reinnervation to about 9 times its control
      level, remained high for about one week, and declined towards normal thereafter.
      If the nerve was crushed close to the muscle and reinnervation occurred very
      rapidly, the extrajunctional increase of the A12 AChE form still occurred but was
      less pronounced than after late reinnervation. In contrast, a transient paralysis
      of the SOL muscle due to acetylcholine receptor blockade by alpha-bungarotoxin,
      followed by spontaneous recovery of muscle activity after 3-5 days, did not
      revert AChE regulation into an immature state. Disuse of the SOL muscle caused by
      leg immobilization, which is known to change the tonic pattern of neural
      stimulation of the SOL muscle into a phasic one, did not prevent the reversion of
      AChE regulation during reinnervation. This indicates that neural stimulation
      pattern is not crucial for this reversion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500377
TI  - Purine and pyrimidine nucleotides activate distinct signalling pathways in PC12
      cells.
AB  - The role of extracellular nucleotides in intracellular signalling and
      neurosecretion was assessed in PC12 cells. Activation of phospholipase C and
      increased [Ca2+]i were mediated by purinoceptors with an agonist potency profile,
      ATP approximately UTP > 2-methylthioadenosine triphosphate (2-MeSATP), typical of
      P2U. ATP also evoked a rapid acidification followed by a more gradual
      alkalinization (measured with 2',7'-biscarboxyethyl-5(6)-carboxyfluorescein
      (BCECF)), while UTP induced only a gradual alkalinization. The amiloride analogue
      5-(N-ethyl-N-isopropyl)amiloride (EIPA) attenuated the alkalinization phase
      suggesting activation of the Na+/H+ exchanger by ATP and UTP. Using bisoxonol and
      [3H]tetraphenylphosphonium ([3H]TPP+) as potential-sensitive probes, we showed
      that while ATP rapidly depolarized PC12 cells in an Na(+)-dependent manner, UTP
      evoked a much reduced and delayed response. The potency profile (ATP
      approximately 2-MeSATP approximately adenosine 5'-O-(3-thiotriphosphate) (ATP
      gamma S) >> UTP, alpha, beta-methyleneATP) suggested involvement of a receptor
      subtype distinct from P2U. Secretion of endogenous dopamine was also assessed.
      Those nucleotides that induced depolarization (ATP, 2-MeSATP, ATP gamma S) were
      also the most potent secretagogues. UTP was ineffective. Our results suggest that
      ATP stimulates distinct purinoceptor subtypes and induces neurosecretion through
      the activation of multiple signalling pathways.

PMID- 7500378
TI  - Differentiation is induced in three-dimensional cultures of brain cells
      immortalized by the LAP mammalian regulatory system.
AB  - Immortalized neuroectodermal precursor cell lines were generated from mouse brain
      by the SV40 large T antigen expressed under the control of the LAP (lac
      activating protein) mammalian regulatory system. The LAP system permits the
      reversible expression of T antigen as a function of the exogenous inducer,
      isopropyl-beta-D-thiogalactopyranoside. Immortalized cells can be stably
      maintained in an undifferentiated state in monolayer cultures. Cell lines
      expressed the early neurofilament-like protein nestin, but not markers
      characteristic for mature cells such as the neurofilament light protein and glial
      fibrillary acidic protein. Downregulating the LAP-controlled T antigen with
      isopropyl-beta-D-thiogalactopyranoside was not sufficient to induce
      differentiation. However, when cells formed three-dimensional aggregates,
      differentiation to a neuronal phenotype occurred, indicating that cell-cell
      interaction plays an important role in their differentiation. Cells in aggregates
      did not proliferate, even in the presence of T antigen, suggesting that an
      aggregation-induced signal to cease growth was dominant over the growth signal of
      T antigen. Further morphological differentiation was induced by basic fibroblast
      growth factor. These immortalized cells should facilitate molecular and cellular
      studies concerned with the mechanism of commitment, fate determination, and
      mitotic arrest of neuronal precursor cells in the developing mammalian CNS.

PMID- 7500379
TI  - On identifying a second molecular antagonistic mechanism operative at the glycine
      receptor.
AB  - We used molecular modeling techniques to examine six reported antagonists of
      glycine with varying Ki values against strychnine. We found the data suggest two
      groups operating with different mechanisms. In group 1 (strychnine, brucine,
      Pitrazepin, and bicuculline methobromide) the antagonist contains two or three
      sites that can electrostatically bind to the three comparable groups of opposite
      charge in the recognition site where the natural neurotransmitter binds, thus
      opening the chloride channel. In addition, when in this position, the antagonist
      is able to also block the now opened chloride channel with a different portion of
      its structure. In many cases, this involves an interaction between a carbonyl
      group on the antagonist and the guanidinium group of arginine which is part of
      the polypeptide segment of the outer mouth of the chloride channel (Grenningloh
      et al., Nature 330:25-26, 1987). In group 2 (R5135 and 1,5-diphenyl-3,7
      diazaadamantan-9-ol) the antagonist contains charged sites but when one of these
      molecules attaches to the recognition site, the chloride channel is not opened.
      In addition, R5135 contains a carbonyl group which attaches to arginine as
      pointed out in the text, whereas 1,5-diphenyl-3,7-diazaadamantan-9-ol contains a
      phenyl group that can block the channel.

PMID- 7500380
TI  - Protein kinase C-alpha and -epsilon are enriched in growth cones of
      differentiating SH-SY5Y human neuroblastoma cells.
AB  - SH-SY5Y cells differentiate into neuronal-like cells and express marker proteins
      like growth-associated protein (GAP-43) and neuropeptide tyrosine when treated
      with a low concentration (16 nM) of the phorbol ester 12-O-tetradecanoylphorbol
      13-acetate (TPA) in the presence of growth factors or serum. Both control and
      differentiated cells expressed protein kinase C-alpha (PKC-alpha), PKC-epsilon,
      and PKC-zeta as revealed by Western blot analyses, but the subcellular
      distribution of the three isoforms was not uniform, indicating specific localized
      functions of the enzymes. In growth cones prepared from differentiating cells PKC
      alpha and PKC-epsilon were enriched. In contrast, PKC-zeta was more evenly
      distributed within the differentiating cell. Cells treated with a high
      concentration of TPA (1.6 microM) differentiate poorly and continue to
      proliferate. In those cells, PKC-alpha and PKC-epsilon were found to be down
      regulated while PKC-zeta remained present. Thus, down-regulation of PKC-alpha and
      PKC-epsilon appears to be incompatible with neuronal differentiation of SH-SY5Y
      cells. These cells also differentiate when treated with a combination of basic
      fibroblast growth factor and insulin-like growth factor I. Growth cones isolated
      from such cells are also enriched in PKC-alpha and PKC-epsilon, but not in PKC
      zeta. Based on the subcellular distribution of PKC-alpha and epsilon, and that
      PKC substrates like GAP-43 and pp60c-src are enriched in SH-SY5Y growth cones, a
      role during neurite growth is suggested.

PMID- 7500381
TI  - Neuronal differentiation of P19 embryonal carcinoma cells in defined media.
AB  - The P19 embryonal carcinoma cell line is a useful model system for analyzing the
      factors that regulate neuronal differentiation. In order to analyze the extrinsic
      factors that are involved in differentiation, it is necessary to carry out
      experiments in fully defined media. Here we have investigated the neuronal
      differentiation of P19 cells in two defined media. Cells that are propagated and
      induced with retinoic acid in standard serum-containing medium are capable of
      differentiating into neuron-like cells in N2 medium. Dividing fibroblast-like
      cells also appeared in these cultures. After about 10 days in culture in N2
      medium, the great majority of neuron-like cells died. On the other hand,
      culturing induced cells in N2 medium for 5 days and then switching to a defined
      medium consisting of Neurobasal medium plus B27 supplement allowed the neuron
      like cells to survive for prolonged periods of time. This defined medium thus
      provides a suitable system for analyzing extrinsic factors that affect the
      survival and differentiation of P19 neurons. P19 cells induced with retinoic acid
      and plated in N2 were exposed to bFGF and EGF, which are known to be mitogens for
      neuronal precursor cells. Both growth factors were mitogenic for a subpopulation
      of the induced cells. In separate experiments, cells cultured in N2 in the
      presence of RA were induced to differentiate into neuron-like cells.

PMID- 7500382
TI  - Differential expression of heat shock protein HSP27 in human neurons and glial
      cells in culture.
AB  - HSP27 expression was investigated in cultured neurons and glial cells isolated
      from fetal human brains using immunoblotting and immunocytochemistry. Under
      unstressed conditions, HSP27 was identified at a high level in astrocytes (>
      99%), at a low level in neurons (7%), and at a minimally detectable level in
      microglia (< 1%), whereas it was undetectable in oligodendrocytes. Under these
      conditions, HSP27 was located in the cytoplasm, fractionated into the Triton X
      100-soluble phase, and composed chiefly of the basic isoform (HSP27a). After
      exposure to heat stress (43 degrees C/90 min), the level of HSP27 expression was
      not altered in astrocytes but was elevated significantly in neurons (11-21%) and
      microglia (4-7%) during 8-48 hr postrecovery periods, while it remained
      undetectable in oligodendrocytes. In addition, various human neural cell lines
      exhibited differential patterns of HSP27 expression under unstressed and heat
      stressed conditions. Following heat shock treatment (45 degrees C/30 min),
      granular aggregates of HSP27 were identified in the cytoplasm of astrocytes.
      Under heat-stressed conditions, HSP27 was distributed within the Triton X-100
      insoluble fraction associated with an increase in two more acidic isoforms
      (HSP27b and HSP27c). HSP27 and alpha B-crystallin were coexpressed in astrocytes
      under unstressed and heat-stressed conditions. When astrocytes were exposed to
      known HSP27 inducers, hydrogen peroxide and cysteamine reduced the synthesis of
      HSP27, while estradiol showed no effects. The differential patterns of
      constitutive and heat-induced expression of HSP27 in cultured human neurons and
      glial cells suggest that the cellular mechanisms by which HSP27 expression is
      regulated are different among various cell types in the human central nervous
      system.

PMID- 7500383
TI  - Three isoforms of human myelin basic protein: purification and structure.
AB  - Myelin basic protein (MBP) occurs in multiple forms. Three of these isoforms from
      human MBP (HMBP) have been highly purified. HMBP, component 1 (18.5 kDa HMBP-1),
      was purified by ion-exchange chromatography at pH 10.6 in 2 M urea. During this
      ion-exchange chromatography, a fraction (Fraction 3), which contained HMBP
      component 3 (monophosphorylated or deamidated 18.5 kDa) and 17.2 kDa HMBP, was
      collected and further purified by fast protein liquid chromatography, which
      separated 17.2 kDa HMBP and HMBP component 3. When the latter was subjected to
      limited thrombic digestion, all of HMBP component 3 not phosphorylated at
      theonine 98 was cleaved. This digestion mixture was separated on Sephadex, and
      yielded pure component 3, monophosphorylated at theonine 98 (HMBP 3pT98), for
      which phosphate analysis yielded approximately 1 mole P/mole protein, and NMR
      showed only one phosphorylation site present. Circular dichroism (CD) studies
      were carried out on dilute solutions of HMBP-1 (18.5 kDa), 17.2 kDa HMBP, and
      HMBP3pT98 (phosphorylated 18.5 kDa). The CD spectrum of HMBP-1 was similar to
      that reported for rabbit MBP-1 and bovine MBP-1, but the spectra of 17.2 kDa HMBP
      and HMBP 3pT98 were distinctly different from HMBP-1. When analyzed by best-fit
      computations, 17.2 kDa HMBP showed about a 9% increase of ordered structure, and
      a greater increase, about 12%, was estimated for HMBP3pT98, attributable to beta
      structure and beta turn.

PMID- 7500384
TI  - Second generation cholinesterase inhibitors: effect of (L)-huperzine-A on
      cortical biogenic amines.
AB  - L-Huperzine-A (Hup-A), a natural cholinesterase inhibitor (ChEI) derived from the
      Chinese herb Huperzia serrata, was administered systemically (i.p.) or locally
      through the microdialysis probe into the rat cortex. Systemic Hup-A significantly
      increased acetylcholine (ACh) levels above baseline at doses of 0.1, 0.3, and 0.5
      mg/kg; the increases were 54%, 129%, and 220%, respectively. Norepinephrine (NE)
      and dopamine (DA) levels were also increased 121% and 129% above baseline at 0.3
      mg/kg, and 143% and 153% at 0.5 mg/kg. Peak cholinesterase (ChE) inhibition was
      23% at 60 min with the 0.3 mg/kg dose. Huperzine-A, perfused through the
      microdialysis probe, produced a maximal increase of ACh levels of 3090% and 7790%
      at concentrations of 5 and 50 microM. The ACh increase seen at both
      concentrations lasted at least 6 hr. At the 5-microM dose, NE and DA were
      increased by 214% and 386%; at the 50-microM dose, NE and DA were increased by
      216% and 1141%. There were no changes of 5-HT levels. With local administration
      (via the probe), both doses produced facial-forelimb seizures that lasted
      throughout the perfusion. Our results show that Hup-A is a potent inhibitor of
      ChE which penetrates into the brain and produces a dose-dependent increase of
      ACh, NE, and DA in rat cortex. This effect is seen with both systemic and local
      intracerebral administration, suggesting cortical as well as subcortical effects
      of the drug.

PMID- 7500385
TI  - Distribution of erb-B2, erb-B3, and erb-B4 in the developing avian nervous
      system.
AB  - The neuregulin proteins (GGF/ARIA/NDF/Heregulin) are pleiotrophic growth and
      differentiation factors whose receptors, erb-B2, erb-B3, and erb-B4, are members
      of the epidermal growth factor receptor family of receptor tyrosine kinases. With
      western blots, we have examined the developmental and regional distribution of
      these receptors within the brain and sciatic nerve of chick embryos. The
      receptors erb-B2, erb-B3, and erb-B4 are developmentally and spatially regulated
      within the nervous system. In addition, cultures enriched for neurons or glia
      indicate that erb-B2 and erb-B4 are found in both neurons and glia, whereas erb
      B3 is found in glia alone.

PMID- 7500386
TI  - GapIII, a new brain-enriched member of the GTPase-activating protein family.
AB  - Ras GTPase-activating proteins (GAPs) are negative regulators of ras, which
      controls proliferation and differentiation in many cells. Ras GAPs have been
      found in a variety of species from yeast to mammals. We describe here a newly
      identified mammalian GAP, GapIII, which was obtained by differential screening of
      a rat oligodendrocyte cDNA library. GapIII putatively encodes a 834 amino acid
      protein with a predicted molecular weight of 96 kDa, which contains a consensus
      GAP-related domain (GRD). The protein encoded by this cDNA has high homology with
      Gap1m, which was recently identified as a putative mammalian homolog of
      Drosophila Gap1. These proteins contain three structural domains, an N-terminal
      calcium-dependent phospholipid binding domain, GRD, and a C-terminal PH/Btk
      domain. Because of the sequence homology and the structural similarities of this
      protein with Gap1m, we hypothesize that GapIII and Gap1m may be members of a
      mammalian GAP gene family, separate from p120GAP, neurofibromin (NF1), and IQGAP.
      To confirm the GapIII protein activity, constructs containing different GapIII
      GRD domains were transformed into iral mutant yeast to determine their relative
      ability to replace IRA1 functionally. Constructs that contained essentially the
      full-length protein (all three domains), the GRD alone, or the GRD plus PH/Btk
      domain suppressed heat shock sensitivity of ira1, whereas constructs that
      contained the GRD with part of the PH/Btk domain had only a weak ability to
      suppress heat shock sensitivity. These results suggest that the GapIII GRD itself
      is sufficient to down-regulate ras proteins in yeast. Expression of GapIII mRNA
      (4.2 kb) was examined by Northern analysis and in situ hybridization. This mRNA
      was expressed at highest levels in the brain, where its expression increased with
      development. Lower levels of the mRNA were expressed in the spleen and lung.
      Among neural cells, GapIII mRNA was expressed in neurons and oligodendrocytes,
      but not in astrocytes. Interestingly, the expression pattern in brain is
      reminiscent of type 1 NF1 expression reported by Gutmann et al. (Cell Growth
      Differ in press, 1995). We propose that in addition to p120GAP and neurofibromin,
      the GapIII/Gap1m family may be important for modulating ras activity in neurons
      and oligodendrocytes during normal brain development and in particular in the
      adult brain.

PMID- 7500387
TI  - Usefulness of physicians functioning as emergency medical technicians.

PMID- 7500388
TI  - Preventable death evaluation of the appropriateness of the on-site trauma care
      provided by Urgences-Sante physicians.
AB  - The study is based on 44 preventable deaths occurring in a cohort of 360 patients
      with major trauma. These cases were reviewed by a committee of nine experts. The
      mean Injury Severity Score (ISS) was 28, and most cases had injuries to the
      head/neck (68%) and chest (64%). The mean (+/- SD) observed prehospital times,
      and those considered the maximum allowable by the committee, were 40.6 +/- 12.0
      minutes for head/neck injuries and 23.9 +/- 12.2 minutes for chest injuries (p <
      0.05). Intravenous (i.v.) lines were started in 38 (86%) of the patients. The
      committee classified this procedure as harmful for 16 (42%) and neutral for 19
      (50%). Among the 18 (46%) that were intubated, this intervention was considered
      harmful for 17% and neutral for 39%. In two of the three patients for whom a
      pneumatic antishock garment was applied, this procedure was considered harmful.
      Of the 34 patients that required direct transport at a level I trauma center, 50%
      were transferred to such a hospital. These results show significant prehospital
      delays and high rates of inappropriate IV line initiation and intubation in
      trauma patients receiving on-site care by physicians. We conclude that
      prehospital care protocols for trauma patients should emphasize prompt transport
      and specific on-site care algorithms.

PMID- 7500389
TI  - An evaluation of patient outcomes before and after trauma center designation
      using Trauma and Injury Severity Score analysis.
AB  - In June 1990, the Ministry of Health designated 11 hospitals throughout Ontario
      to be lead hospitals in trauma care. An integral part of a trauma system is the
      evaluation of care, in particular, outcome of the trauma patients. The Trauma and
      Injury Severity Score (TRISS) methodology, which offers a standard approach for
      evaluating outcomes for different populations of trauma patients, was used to
      determine if there was an improvement in outcomes after the designation of trauma
      centers of patients involved in motor vehicle crashes (ICD-9-CM, E810.0-825.9),
      with an Injury Severity Score > 12 for two 12-month periods: one predesignation
      (1989/1990) and one postdesignation (1992/1993). The Revised Trauma Score, Injury
      Severity Score, age, and outcome were calculated or abstracted from the hospital
      chart of each patient at the trauma center. The probability of survival of each
      patient, the z- and W-statistics of both years were calculated. A measurable
      improvement was shown in z-statistics between the 2 years from z = -0.40
      predesignation to z = +0.72 postdesignation. When the bias introduced by patients
      intubated before arrival at the trauma center being excluded from TRISS analysis
      was removed, using a TRISS-like (as per Offner et al: J. Trauma 32:32, 1992)
      logistic regression equation that allows analysis of intubated patients, the
      improvement was even greater, with z = +1.34 predesignation and z = +2.97
      postdesignation. Only the statistically significant z-score of the postdesignated
      year required the W-score to be calculated, W = +5.60.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7500390
TI  - Lowering hospital charges in the trauma intensive care unit while maintaining
      quality of care by increasing resident and attending physician awareness.
AB  - OBJECTIVE: The goal of this study was to determine if trauma intensive care unit
      (TICU) charges could be reduced through informal daily bedside resident-attending
      physician discussions regarding relative patient costs of diagnostic and
      therapeutic alternatives. DESIGN: This was a prospective pre- and
      postinterventional study. SETTING: The study took place in a TICU in a level I,
      community-based, university-affiliated teaching hospital. PATIENTS: Ninety-one
      consecutive patients were admitted to the TICU during a 6-month period. MATERIALS
      AND METHODS: The TICU charges were tracked over two consecutive 3-month periods.
      The first 3 months served as control. No attempt was made to alter cost of care,
      and residents were unaware that a study was in progress. During the ensuing 3
      month period, attendings explicitly discussed with residents relative costs of
      diagnostic and therapeutic interventions in an attempt to lower charges.
      Composition of the surgical trauma team remained constant throughout the study.
      MEASUREMENT AND MAIN RESULTS: The median and mean age, Injury Severity Score,
      intensive care unit length of stay, and sex ratio were not statistically
      different between the two study groups. Total median daily charges of the
      postintervention group were reduced over the control group by $818/intensive care
      unit day (p = 0.0002). The major categories in which charges were reduced
      included medications ($151/day, p = 0.003), laboratory tests ($120/day, p =
      0.072), chest x-ray films ($61/day, p = 0.001), respiratory therapy ($185/day, p
      = 0.21), and miscellaneous charges ($141/day, p = 0.055). Mortality rates and
      number of major complications were not statistically different between groups.
      CONCLUSIONS: Increased awareness of cost factors and specific attempts to achieve
      patient cost reduction resulted in a demonstrable decrease in daily TICU charges,
      without compromising the quality of care.

PMID- 7500391
TI  - The politics of trauma system development.
AB  - Federal and state policymakers have turned to health planning programs as a means
      to rationalize the delivery of health care services in the United States for over
      3 decades. Early federal initiatives such as the Comprehensive Health Planning
      Act of 1966 and the Health Planning and Resource Development Act of 1974 were
      widely criticized for their inability to control costs effectively or to increase
      the efficiency of health services delivery. The design and implementation of the
      federal government's latest entry into health planning, the Trauma Care System
      Planning and Development Act of 1990 (Pub. L. 101-590), suggests that federal and
      state officials are poised to repeat the mistakes that plagued previous planning
      programs. The implementation of Pub. L. 101-590 illustrates the dilemmas that
      federal and state officials must confront in achieving effective representation
      and ensuring active participation in the planning process. Successful regional
      and statewide planning ventures must devise strategies to overcome the inherent
      collective action problems associated with cooperative solutions to underserved
      populations. Contemporary approaches to health planning, however, are based on a
      number of questionable assumptions. The creation of new institutional structures
      merely shifts the venue for existing conflicts among health providers, third
      party insurers, and other participants in the health policymaking process to a
      new arena. In addition to examining possible alternatives for improving current
      trauma system planning initiatives, this paper presents a new paradigm for
      designing and implementing state and federal planning programs.

PMID- 7500392
TI  - The value of the medical examiner as a member of the multidisciplinary trauma
      morbidity-mortality committee.
AB  - The multidisciplinary trauma peer review process collects, reviews, discusses,
      and collates all morbidities and mortalities of injured patients to institute
      corrective action in a timely manner. The resultant remedial activity may include
      professional education, physician counseling, restriction of privileges, or
      changes in the trauma care system. Effective corrective action necessitates
      timely data input from the postmortem examination. Faced with an inordinate
      delay, skimpy reports, and expense in obtaining such reports from the medical
      examiner's office, the chief medical examiner was invited to become a member of
      the peer review committee. During a 12-month interval as a full-fledged member of
      the peer review process, the medical examiner was able to provide complete verbal
      reports on all deaths resulting in a synergistic benefit to the peer review
      process and to the medical examiner office. Two of 53 nonpreventable deaths were
      reclassified as possibly preventable in one and preventable in the other. Four of
      15 possibly preventable deaths were reclassified based on the medical examiner
      report. In turn, the physician members of the team were able to augment the
      medical examiner's knowledge in certain areas that were critical for his analysis
      of accidents or homicide. Based on these findings, the medical examiner is
      recommended as a participating member of the trauma peer review committee.

PMID- 7500393
TI  - Effect of valvular heart diseases, migraine headaches, and perianal diseases on
      the risk of involvement in motor vehicle crashes.
AB  - Impaired health can interfere with driving performance. We have launched this
      investigation to identify in professional military drivers health parameters that
      might be associated with involvement in motor vehicle crashes (MVCs). All Israel
      Defense Forces professional male drivers (N = 5,605) conscripted into compulsory
      military service between April 1, 1988 and April 1, 1990 were divided into two
      groups according to whether (N = 1,300) or not (N = 4,305) the driver was
      involved in MVCs during the same time frame. Using the multivariate Cox model, a
      significant association was shown between involvement in MVCs and the following
      health parameters: mild-to-moderate valvular heart disease (p = 0.0002, chi 2 =
      13.89), migraine headaches (p = 0.009, chi 2 = 6.91), and perianal diseases (p =
      0.006, chi 2 = 7.44). We hypothesize that interference with the driver's
      performance level may be a result of the discomfort associated with those
      clinical conditions. It is possible that interference with the personal
      performance level decreased the ability of the driver to cope with the specific
      driving task demands and resulted in the involvement of the driver in MVCs. We
      suggest that because of the high social and economic costs associated with road
      accidents, it is important to investigate further the association of involvement
      in MVCs and health problems. If our findings are confirmed in the future studies,
      intervention programs to reduce MVC rates would be suggested and conducted among
      professional drivers.

PMID- 7500394
TI  - Children's traffic safety program: influence of early elementary school safety
      education on family seat belt use.
AB  - HYPOTHESIS: Young children can learn safety behavior in the public school system.
      These children will modify family seat belt use. SETTING DESIGN: This is a
      prospective cohort analytic study conducted in a 50,000 square mile regionalized
      trauma center referral area. METHODS: A school-based injury prevention program
      targeting kindergarten through second-grade (K-2) students addressed four aspects
      of traffic safety: seat belt use, pedestrian and bicycle safety, school bus
      safety, and unsafe rides. After inservice instruction, teachers taught the
      program over a 10-week period. A simultaneous community traffic safety program
      was conducted through the media. Family seat belt use was monitored by blinded
      observation at six study schools and one control school. Income level of schools
      was characterized as low or high, based on student use of federal lunch
      subsidies. School program implementation was defined as good or poor, based on
      adherence to teaching protocol. RESULTS: A total of 68,650 K-2 students have
      completed this traffic safety program during 1990 to 1994. During the study year
      (1992 to 1993), 25,900 students completed the program taught by 1,400 teachers in
      95 schools. A total of 5,936 observations of seat belt use were made in seven
      schools. Income stratification delineated a subset of these schools in which seat
      belt use increased by 86% (p = 0.01). Half of the schools failed to follow
      protocol, and no change in seat belt use was observed. CONCLUSIONS: (1) School K
      2 safety education improves family seat belt use, (2) low income schools should
      be targeted, and (3) strict adherence to the teaching protocol is essential.

PMID- 7500395
TI  - Organ injury scaling. VI: Extrahepatic biliary, esophagus, stomach, vulva,
      vagina, uterus (nonpregnant), uterus (pregnant), fallopian tube, and ovary.

PMID- 7500396
TI  - Cardiopulmonary effects of raised intra-abdominal pressure before and after
      intravascular volume expansion.
AB  - The cardiopulmonary effects of acutely elevated intra-abdominal pressure (IAP)
      were studied in a porcine model to help define more clearly IAP effects in
      patients with trauma. IAP was increased in six anesthetized swine by intra
      abdominal instillation of isotonic ethylene glycol up to an IAP of 25 mm Hg above
      baseline. Systemic and pulmonary hemodynamic parameters were measured, as well as
      the effects on bladder pressure, pleural pressure, and pulmonary function. At IAP
      of 25 mm Hg above baseline, intravascular volume expansion with saline was
      administered to return the cardiac index (CI) to baseline. Raising IAP correlated
      with measured bladder pressures (r = 0.9, p = 0.001). At IAP of 25 mm Hg, CI was
      significantly decreased (p < 0.05, analysis of variance (ANOVA); 3.6 +/- 0.3 vs.
      2.2 +/- 0.3 L/min/m2); whereas wedge, pulmonary arterial, and pleural pressures
      were all elevated (p < 0.05, ANOVA). However, transarterial wedge pressure (wedge
      -pleural pressure) declined nonsignificantly with increasing IAP. Raised IAP
      caused impaired pulmonary function with a decreased (p < 0.05, ANOVA) PaO2 and
      increased (p < 0.05, ANOVA) PaCO2. Despite the elevated wedge pressure, fluid
      resuscitation returned CI to baseline. These data clarify the hemodynamic changes
      associated with raised IAP and indicate that care must be taken in interpreting
      hemodynamic measurements to determine intravascular fluid status in patients with
      elevated IAP.

PMID- 7500397
TI  - Small bowel injuries: mechanisms, patterns, and outcome.
AB  - OBJECTIVES: To determine the relationship between mechanism of injury (MI),
      operative management (OM), and outcome for traumatic jejunal and ileal wounds
      using an aggressive diagnostic, therapeutic, and support protocol. METHODS:
      Medical records for patients discharged with small bowel injuries from the Trauma
      Service between 1988 and 1992 were reviewed. The MI, presence of shock, method of
      diagnosis, OM, morbidity, and mortality were analyzed. RESULTS: Seventy patients
      had jejunal and/or ileal injuries. Blunt mechanisms caused injury in 33%, whereas
      the rest were penetrating wounds. Twenty-one diagnostic peritoneal lavages
      facilitated diagnosis (71% positive by tap). Ninety-six percent of the patients
      were explored within 3 hours of admission. Multiple perforations of jejunum were
      the most common injury of the small bowel. Using the Organ Injury Scale, grade
      III and IV wounds were statistically more common with penetrating injuries. Most
      of the injuries were managed with resection and stapled anastomosis, even in the
      presence of shock. CONCLUSIONS: There is a significant difference in MI and OM
      for small bowel wounds. Resection and stapled anastomosis is safe even in the
      presence of shock. Mortality and morbidity are related to associated injuries.

PMID- 7500398
TI  - Traumatic chest lesions in patients with severe head trauma: a comparative study
      with computed tomography and conventional chest roentgenograms.
AB  - In patients with severe craniocerebral trauma, who need a continuous positive
      pressure breathing, the detection of pulmonary and mediastinal traumatic lesions,
      especially pneumothorax, may alter the management. The aim of this study is to
      evaluate the efficiency and accuracy of conventional supine chest roentgenograms
      to detect the associated traumatic chest lesions in severe craniocerebral trauma
      and to compare their value as a diagnostic method for the identification of
      unsuspected lesions with a limited chest computed tomographic (CT) examination.
      Forty-seven consecutive patients with severe craniocerebral trauma underwent head
      CT and a prospective limited CT examination of the thorax in the same session.
      Nine patients (19.1%) presented a pneumothorax, bilateral in one case. Six
      pneumothoraces (60%) were identified both on conventional chest roentgenograms
      and CT, whereas in four cases (40%), the lesion was only detectable on CT. The CT
      study also showed 31 areas of pulmonary parenchymal contusions in 19 subjects
      (40%), whereas the conventional chest roentgenograms demonstrated 17 areas of
      contusions in 11 (23%) subjects. One thoracic aorta and one right diaphragm
      rupture were detected on CT study. On the conventional chest roentgenograms the
      mediastinal vascular injury was overlooked, whereas the right diaphragmatic
      rupture was highly suspected. The limited chest CT examination supplied
      additional information in 30% of patients. In 12.7% of patients, this information
      was clinically significant enough to alter the management. In patients with
      severe craniocerebral trauma evaluation of associated chest trauma by a
      supplementary limited chest CT, examination provides more and precise information
      about the size and severity of mediastinal and pulmonary lesions with a superior
      detectability of pneumothorax.

PMID- 7500399
TI  - Exclusion of aortic tear in the unstable trauma patient: the utility of
      transesophageal echocardiography.
AB  - OBJECTIVE: The goal of this study was to investigate the value of biplanar
      transesophageal echocardiography (TEE) as a screening tool for aortic tear in
      unstable trauma patients. METHODS: During a 1-year period, a prospective trial to
      exclude aortic tear was conducted at a level I trauma center. Ten of 53 patients
      (19%) sustaining severe blunt thoracic trauma were deemed too unstable to undergo
      safe transport to aortography and underwent TEE. Mechanism of injury was motor
      vehicle crash in eight patients and pedestrians struck in two. Patients had a
      mean Injury Severity Score = 34 (range, 17 to 59) and mean age = 43 years (range,
      18 to 77). Indications for aortic tear evaluation were chest x-ray findings in
      seven and mechanism of injury alone in three. Patients were not transportable
      because of hemodynamic instability in five individuals, severe unstable head
      injury in three individuals, and unstable cervical spine fracture in two
      individuals. RESULTS: Transesophageal echocardiography was performed in the
      emergency department in one instance, in the operating room in one instance, and
      in the surgical intensive care unit in the remaining eight instances. Patients
      underwent the procedure less than 8 hours after admission in seven and more than
      48 hours after admission in three. One patient had a complication during TEE
      (ventricular dysrhythmias). In one of ten patients, TEE was positive. This
      patient required medical management (beta-blockade) for aortic tear until severe
      hypoxia secondary to pulmonary contusion improved after 36 hours. Repair of
      aortic tear was then successfully performed. CONCLUSIONS: The TEE procedure is
      valuable in identifying aortic injury in high-risk trauma patients who are too
      unstable to undergo transport to the aortography suite.

PMID- 7500400
TI  - Effect of hyperventilation, mannitol, and ventriculostomy drainage on cerebral
      blood flow after head injury.
AB  - Therapies to lower intracranial pressure (ICP) after traumatic brain injury (TBI)
      include hyperventilation (HV), intravenous mannitol (IM), and cerebrospinal fluid
      drainage from a ventriculostomy (DV). To determine the effects of these therapies
      on cerebral blood flow (CBF), fiberoptic oximetry was used to measure jugular
      venous O2 saturation (SjvO2) as an index of the CBF to cerebral metabolic rate
      for O2 (CMRO2) ratio after IM (25 g IV for more than 5 min), DV (3 min), or HV
      (increase respiratory rate by 4) therapy for elevated ICP. Assuming CMRO2 is
      constant, changes in SjvO2 reflect changes in CBF. Continuous measurements of
      SjvO2, ICP, blood pressure, arterial O2 saturation, and end-tidal CO2 were
      obtained in 22 patients with a Glasgow Coma Scale score of 5.3 +/- 0.4 (mean +/-
      SD) in the first 5 days after TBI. Therapy was initiated a total of 196 times
      when ICP was > 15 mm Hg for > 5 minutes, and measurements made at 20 minutes
      after treatment were compared with those made just before. After DV, ICP fell in
      90% of the observations by 8.6 +/- 0.7 mm Hg (mean +/- SEM, n = 119); after IM,
      ICP fell in 90% of the observations by 7.4 +/- 0.7 mm Hg (n = 43); and after HV,
      ICP fell in 88% of the observations by 6.3 +/- 1.2 mm Hg (n = 14). In patients
      where ICP fell, SjvO2 increased by 2.49 +/- 0.7% saturation (from 68.0 +/- 1.3%)
      with IM, but only by 0.39 +/- 0.4% saturation (from 67.2 +/- 0.9%) with
      DV.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500401
TI  - Transpyloric passage of feeding tubes in patients with head injuries does not
      decrease complications.
AB  - Early enteral nutrition is reported to improve outcome of patients with severe
      closed head injuries (CHI). The efficacy and safety of nasoenteric tube (NET)
      feeds, however, has been questioned; the risk of aspiration is the major concern.
      Our purpose was to determine the rate of transpyloric migration, the efficacy of
      adjunctive measures to promote passage, and the effect on pulmonary
      complications. Seventy-four consecutive patients with moderate to severe CHI
      received enteral nutrition. Glasgow Coma Scale (GSC) score was 5.2 on admission
      and 6.9 at 48 hours. NETs were placed an average of 5.6 days after admission; an
      average of three abdominal films per patient were used to assess tube position.
      No patients had endoscopic NET placement during this period. Ten patients
      required fluoroscopic placement after failure to pass spontaneously by 5 days.
      Overall, transpyloric passage was achieved in 32 patients (43%), whereas 42 (57%)
      remained intragastric. There were no differences between the postpyloric and
      intragastric groups in days to full feeding (5 vs. 7 days), ventilator days (11.9
      vs. 12.5), intensive care unit length of stay (15.5 vs. 15.1), or incidence of
      pneumonia (81 vs. 69%) or aspiration (6 vs 7%). Sixty-two patients (83%) were
      transferred to extended care facilities and 50 (68%) were still receiving NET
      feedings. Spontaneous transpyloric passage of NET occurred in less than one-half
      of patients with severe CHI. The routine use of adjunctive measures to promote
      transpyloric passage was not particularly successful, had no obvious benefit, and
      therefore may not be necessary.

PMID- 7500402
TI  - The need for aggressive nutritional intervention in the injured patient: the
      development of a predictive model.
AB  - Early nutritional intervention has been advocated in trauma patients. We have
      developed a model to identify those patients who will most benefit from the
      invasive and costly measures that are required to provide injured patients with
      early enteral feedings. Four hundred forty-two patients admitted to a level I
      trauma center during a 2-month period were evaluated using 21 clinical variables.
      Time to tolerance of a regular diet was used as the dependent variable in a step
      wise regression, and then the selected variables were used to build a
      classification and regression tree to predict tolerance of a regular diet within
      5 days. Our findings demonstrate that intensive care unit disposition, Injury
      Severity Score, Abdominal Trauma Index, and the need for early surgical
      intervention are important predictors regarding the need for early nutritional
      intervention. When the model was applied to the study population, it had a
      sensitivity of 83%, a specificity of 84%, and an accuracy of 84%.

PMID- 7500403
TI  - Thoracolumbar spine fractures: clinical presentation and the effect of altered
      sensorium and major injury.
AB  - A retrospective review of 145 patients with thoracic or lumbar spine fractures
      from blunt trauma was conducted to identify the clinical presentation of these
      patients. The presence of back pain or tenderness (BPT), neurologic injury,
      altered sensorium from head injury or alcohol intoxication, and concomitant major
      injury were determined. Any delayed or missed diagnoses were analyzed. One
      hundred eighteen (81%) patients complained of BPT on their initial presentation.
      The presence of BPT was significantly higher in those patients without an altered
      sensorium or other major injury. Of the 27 (19%) patients with a negative finding
      of BPT, all (100%) had an altered sensorium, concomitant major injury, or
      neurologic deficit. There were no asymptomatic thoracic or lumbar spine fractures
      in neurologically intact patients with clear sensoriums and no concomitant major
      injuries. These patients do not need routine thoracolumbar radiography.

PMID- 7500404
TI  - Spine and spinal cord injuries in downhill skiers.
AB  - Spine and spinal cord injuries are the most debilitating and costly of serious
      injuries sustained by downhill skiers. We present a series of 126 skiers with
      spine and spinal cord injuries drawn from 636 consecutive injured skiers
      evaluated at one center over an 11-year period. The incidence of spinal injury
      was very low (0.001/1000 skier-days). Eighteen (17%) patients had spinal cord
      injuries associated with their fractures; injuries in the cervical region were
      most likely to involve the spinal cord. The most commonly fractured levels were
      C6, T12 and L1; the most common fracture pattern was compression (38%). One-third
      of all patients had multisystem trauma; those with thoracolumbar injuries were
      much more likely to sustain torso and extremity trauma than those with cervical
      injuries. Information about injury patterns in skiers with spinal injuries should
      aid in the triage and initial evaluation of this blunt trauma population.

PMID- 7500405
TI  - Economic analysis of roentgenogram use in the closed treatment of stable ankle
      fractures.
AB  - Fractures of the ankle are one of the most commonly treated injuries by
      orthopedic surgeons. The adequacy of closed treatment of stable lateral malleolar
      ankle fractures is frequently assessed by repeated roentgenograms. There are no
      standards, nor studies, however, that provide guidelines as to the necessity of
      such roentgenograms. This study was designed to determine the average frequency
      of follow-up roentgenograms in ankle fractures treated by casting, as well as the
      clinical impact of these roentgenograms. The clinical radiographic data base of a
      university hospital was reviewed to identify all ankle fractures treated between
      January 1, 1992 and June 30, 1993. A total of 82 patients satisfied the study
      criteria of having sustained a stable ankle fracture that was treated by closed
      means, with sufficient clinical and radiographic follow-up to assess healing of
      the fracture. All patients healed their fractures at an average of 8.4 weeks (+/-
      3.0 weeks), with weight-bearing initiated at 4.0 weeks (+/- 2.7 weeks). No
      patients developed radiographic evidence of a talar shift during treatment, and
      none required surgery for a failure of closed treatment. At no time did any ankle
      exhibit a significant change in fibular alignment relative to the initial injury
      films. Each patient had an average of 4.5 (+/- 2.0) radiographic studies
      performed throughout their treatment. This study indicates that secondary
      displacement of either the talus or fibula in a stable ankle fracture is very
      unusual. In conjunction with the generally excellent outcome for such fractures,
      this suggests that frequent roentgenograms are not justified on clinical
      grounds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500406
TI  - Influence of reaming versus nonreaming in intramedullary nailing on local
      infection rate: experimental investigation in rabbits.
AB  - The question of whether the impairment of the endosteal blood supply, which is
      induced by nailing with reaming of the medullary cavity, increases the risk of a
      postoperative infection cannot be conclusively answered by studying existing
      literature. The aim of this study was to investigate the effect of medullary
      reaming on the occurrence of local infection based on an infection model in the
      rabbit tibia (n = 44). An infection rate of 50% was found after unreamed nailing,
      as opposed to an infection rate of 64% after medullary reaming. The number of
      bacteria observed after reaming was significantly higher than after nail
      insertion without previous reaming. The differing susceptibilities to infection
      as observed in this model are statistically significant (p < or = 0.05).

PMID- 7500407
TI  - Lateral condylar fractures of the humerus in children: fixation with partially
      threaded 4.0-mm AO cancellous screws.
AB  - Thirty-seven children with fresh, displaced (more than 2 mm in any direction)
      fractures of the lateral condyle of the humerus were treated by open reduction
      and internal fixation with a partially threaded 4.0-mm diameter AO lag screw.
      They were reviewed at a mean follow-up of 4.8 years. Painless, full-elbow
      movements were obtained in 36 cases. Delayed union, with loss of 10 degrees of
      elbow motion, was observed in one case (2.72%). Radiologically, less than 4
      degrees of varus deviation, compared with the contralateral side, was found in
      four cases (10.8%). Mild fishtailing was observed in three cases (8.18%).
      Nonunion, avascular necrosis or clinically significant premature epiphysial
      fusion was not observed. Elbow function was excellent, irrespective of minor
      radiologic abnormalities.

PMID- 7500408
TI  - Using bronchoalveolar lavage to distinguish nosocomial pneumonia from systemic
      inflammatory response syndrome: a prospective analysis.
AB  - OBJECTIVE: Ventilator-associated pneumonia (PN) is difficult to distinguish from
      trauma-induced systemic inflammatory response syndrome (SIRS), especially in
      patients with multiple injuries. Previous work using bronchoscopy and
      quantitative cultures demonstrated significant bacterial growth in about one
      third of patients with clinical evidence of PN. In this prospective study,
      antibiotic therapy for PN was based solely on quantitative bronchoalveolar lavage
      (BAL) cultures. METHODS: Mechanically ventilated trauma patients underwent
      bronchoscopy with BAL when they developed clinical evidence of PN: fever
      (temperature > 100.5 degrees F), white blood cells > 10,000 or > 10% immature
      forms, purulent sputum, and new or changing infiltrate on chest roentgenogram.
      Patients with other infections or those receiving antibiotics for any other
      reason were excluded. Empiric antibiotic therapy for PN was started at the time
      of BAL. If the quantitative cultures revealed > or = 10(5) colony-forming units
      (CFU)/mL, that patient was defined as having PN and was treated. If the cultures
      revealed < 10(5) CFU/mL, that patient was defined as having SIRS, and empiric
      therapy was stopped. RESULTS: Forty-three patients (88% blunt, 12% penetrating)
      underwent bronchoscopy with BAL 55 times. Mean age was 40 and Injury Severity
      Score was 25. Twenty patients had > or = 10(5) CFU/mL (47%) and 23 had < 10(5)
      CFU/mL (53%). There were no differences in age, Injury Severity Score,
      temperature, white blood cell count, or ventilator days before BAL between
      groups. Sixty-five percent of those with SIRS improved after empiric therapy was
      stopped (average 3.3 days), and 35% underwent repeat BAL. Three patients with the
      initial diagnosis of SIRS developed PN (13% of SIRS). Mortality for PN was 15%,
      compared with 17% for SIRS; no deaths were related to antibiotic therapy.
      CONCLUSIONS: SIRS, which can mimic PN, is common in trauma patients. These
      entities can be distinguished by bronchoscopy with BAL. Basing antibiotic therapy
      solely on quantitative BAL cultures is efficacious in trauma patients.

PMID- 7500409
TI  - Recombinant human granulocyte colony-stimulating factor treatment improves
      macrophage suppression of granulocyte and macrophage growth after burn and burn
      wound infection.
AB  - Granulocyte and macrophage production after burn injury or burn wound infection
      is significantly reduced and further compromised by endotoxin (ET). Moreover, the
      macrophage seems to be the major source of this bone marrow suppression. We
      sought to determine if recombinant human granulocyte colony-stimulating factor
      (rhG-CSF), a hematopoietic growth factor that is capable of improving survival
      after experimental burn wound sepsis, altered postburn macrophage-mediated marrow
      suppression. Groups of male BDF1 mice (n = 6 to 10) receiving a 15% total body
      surface area burn +/- infection (B or B + I) with Pseudomonas aeruginosa were
      injected with 100 ng rhG-CSF twice daily. On day 3, peritoneal-elicited
      macrophages (5 x 10(6) cells/mL) from either rhG-CSF-treated or control (5%
      dextrose in water) mice were incubated +/- ET (300 ng/mL). The resultant
      macrophage supernatant was added to cultures of target marrow granulocyte
      macrophage progenitor cells (GM-CFC) at a volume of 1:10. The GM-CFC growth as a
      percentage of cultures not containing macrophage supernatant were compared and
      reductions in the number of GM-CFC taken as an index of marrow suppression.
      Macrophages obtained from B and B + I animals reduced target GM-CFC growth,
      compared with macrophages from normal animals (B vs. normal animals p < 0.05). In
      addition, ET-stimulated macrophages induced further bone marrow suppression for
      all three groups (p < 0.01). Macrophages from granulocyte colony-stimulating
      factor-treated animals caused significantly less bone marrow suppression,
      compared with untreated animals for all groups (p < 0.05 to 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7500410
TI  - Leukocyte modulation inhibits endotoxin-induced disruption of intracellular
      calcium homeostasis.
AB  - OBJECTIVE: Sepsis is associated with disruption of intracellular calcium
      homeostasis. The specific mechanisms responsible for these changes remain
      unclear. This study attempts to modify endotoxin-induced alterations in
      erythrocyte intracellular calcium dynamics through modulation of the activated
      leukocyte and its products. METHODS: Paired anticoagulated whole-blood specimens
      were obtained from healthy adult volunteers (n = 30). Specimens were incubated
      with 2 micrograms/mL endotoxin [lipopolysaccharide (LPS)] or saline control in
      the presence and absence of the white blood cell. Studies were repeated in
      specimens pretreated with allopurinol, superoxide dismutase, and pentoxifylline
      (PTX). After incubation, erythrocytes were separated, washed, and loaded with the
      fluorescent calcium chelator, FURA-2. Free cytosolic calcium concentration was
      determined on 10(6) cells using fluorescent spectroscopy. Values were computer
      calculated every 1.8 seconds for 1 minute, and mean results were used for
      analysis. Differences were evaluated by analysis of variance. RESULTS: The LPS
      resulted in a significant increase in intracellular calcium concentration (LPS
      70.95 nM vs. control 44.04 nM). This increase was dependent on the presence of
      the white blood cell and could not be induced in its absence (control 30.15 -->
      LPS 32.78). Pretreatment inhibited these endotoxin-induced alterations:
      allopurinol, 50.49 nM; superoxide dismutase, 49.12 nM; and PTX, 40.23 nM (p <
      0.01). CONCLUSIONS: Endotoxin induces a significant increase in intracellular
      calcium concentration. This alteration seems to be mediated by activated
      neutrophils and can be ameliorated by both leukocyte modulation (PTX) and free
      radical scavengers.

PMID- 7500411
TI  - Intraosseous regional anesthesia as an alternative to intravenous regional
      anesthesia.
AB  - A series of 109 orthopedic operations was performed under intraosseous regional
      anesthesia on the upper and lower limbs. Anesthesia was satisfactory in 106 of
      the cases; in the other three, inadequate anesthesia was caused by faulty
      technique. The spread of lidocaine into the bone and venous network was
      demonstrated by radiography, and the blood levels after tourniquet release were
      below the toxic level. Intraosseous regional anesthesia proved to be a valuable
      technique to be used whenever intravenous anesthesia fails or is not feasible.
      Injection into cancellous bone (osteoclysis) is easily and quickly performed
      under aseptic conditions, and there were no systemic complications.

PMID- 7500412
TI  - Proximity penetrating extremity trauma: the role of duplex ultrasound in the
      detection of occult venous injuries.
AB  - The diagnosis and management of occult vascular injuries caused by penetrating
      proximity extremity trauma (PPET) remains controversial. Over 18 months, we
      prospectively screened 37 patients (43 lower extremities) with PPET for occult
      arterial and venous injuries using noninvasive studies (physical examination,
      ankle-brachial indices, color-flow duplex ultrasonography (CFD)) and angiography
      (arteriography, venography). Eight isolated, occult venous injuries were detected
      (incidence, 22%). CFD detected seven of eight (88%) venous injuries. Venography
      was technically difficult to perform in this patient population and failed to
      detect four femoral-popliteal vein injuries. Major thromboembolic complications
      (pulmonary embolism, symptomatic deep vein thrombosis, venous claudication)
      occurred in 50% of the patients identified with femoral-popliteal vein injuries.
      Arterial injuries were detected in 4 of 42 (10%) extremities (arteriography, n =
      3; CFD, n = 1) and were clinically benign. We conclude that following PPET, (1)
      isolated, occult venous injuries are common and are associated with significant
      complications and (2) CFD is useful for screening for occult venous injuries.

PMID- 7500413
TI  - Experimental thoracoabdominal airgun wounds in a porcine model.
AB  - The Consumer Product Safety Commission estimates that there are 31,000 airgun
      injuries annually, 19,000 of which occur in children under 14 years of age. Case
      reports in the literature include 235 serious and nine lethal pediatric injuries.
      No experimental model of thoracoabdominal airgun pellet perforation exists. A 60
      pound newly killed pig was selected as a model for pediatric airgun injuries. Two
      commonly available .177-caliber airguns were fired from point blank, 2.5 feet,
      and 5 feet. A chronograph was used to measure impact velocities for pellets fired
      at the already-killed pig. Autopsy study of organ wounding was completed.
      Perforation velocities with point-tip pellets were 407 ft/sec for the thoracic
      wall and 399 ft/sec for the abdomen. Of the 18 pellets shot at the chest, eight
      passed through the chest wall, causing 15 organ injuries. Eleven of the 18
      pellets perforated the abdominal wall, producing 49 organ injuries. CONCLUSION:
      Airguns create serious intracavitary organ injuries in a porcine model. Moreover,
      ballistic research is possible in unusual surroundings, such as a packing plant.

PMID- 7500414
TI  - Treatment of increasing intracranial pressure secondary to the acute abdominal
      compartment syndrome in a patient with combined abdominal and head trauma.
AB  - Acute abdominal compartment syndrome has recently been shown to raise
      intracranial pressure (ICP). This may increase the risk of ischemic neuronal
      damage by decreasing cerebral perfusion pressure. We report the successful
      management of a patient with severe multisystem injury in whom abdominal
      decompression dramatically reduced high ICP unresponsive to medical measures.

PMID- 7500415
TI  - Shock-associated right colon ischemia and necrosis.
AB  - Ischemic complications associated with hemorrhagic shock after blunt or
      penetrating trauma can result in acute renal, pulmonary, or hepatic failure. Less
      well described is the association between hemorrhagic shock and ischemic necrosis
      of the right colon, with only 14 cases reported in the literature. Herein, we
      report three previously healthy young trauma victims with shock-associated right
      colon necrosis. Each patient suffered a period of hypotension after injury.
      Diagnosis and operation took place within 2 days of initial injury in all three
      cases. In each patient, a right colectomy and primary anastomosis was performed
      without complication. Pathologic examination of the resected specimens showed
      ischemic necrosis, but no evidence of vascular thrombosis or embolic occlusion of
      the mesenteric vessels. The etiology of this type of ischemic colitis is not
      clear, but seems to represent a form of nonocclusive mesenteric ischemia.
      Knowledge of this disease process will lead to early recognition, prompt
      treatment, and a satisfactory outcome.

PMID- 7500416
TI  - Posttraumatic chylous ascites in a child: recognition and management of an
      unusual condition.
AB  - Chylous ascites is an extremely rare and often unrecognized complication of
      abdominal trauma in children. The management of this condition has traditionally
      been nonsurgical, but the success rate with nonoperative treatment is not always
      satisfactory. A case of posttraumatic chylous ascites in an abused toddler is
      presented, with emphasis on the diagnosis and treatment of this rare disorder.

PMID- 7500417
TI  - A combination of Vicryl and Marlex mesh: a technique for abdominal wall closure
      in difficult cases.
AB  - The circumstances in which it is unsafe or impossible to perform primary fascial
      closure are becoming more frequent. Five cases are reported using a combination
      of Vicryl and Marlex mesh, such that the Vicryl mesh prevents enterocutaneous
      fistulae and the Marlex mesh prevents late ventral hernias.

PMID- 7500418
TI  - Buckshot colic: case report and review of the literature.
AB  - Three weeks after a shotgun wound to the chest and abdomen, a patient developed
      acute ureteral colic caused by a migrating shotgun pellet. The pellet passed
      spontaneously. A search of the literature revealed 25 similar cases of this
      unusual complication of missile injuries to the abdomen. These cases are reviewed
      and analyzed. Ureteral obstruction from migrating retained missiles is an unusual
      complication of missile injuries to the abdomen. Cases have been described
      occurring after shotgun, gunshot, and shrapnel wounds. Cases involving bullets
      and shrapnel fragments usually have had long latent periods after the initial
      injury and required surgery to remove the obstructing projectile. In contrast,
      cases of "buckshot colic" from shotgun pellets present earlier and often resolve
      with spontaneous passage of the pellet. The following report illustrates how
      conservative management can be successful in cases of "buckshot colic."

PMID- 7500419
TI  - Management of thoracic duct injury associated with fracture-dislocation of the
      spine following blunt trauma.
AB  - Thoracic duct injuries accompanying blunt thoracic trauma are rare. A significant
      number of these lesions, however, are associated with fracture-dislocation of the
      spine. In this report, we discuss the surgical management of chylothorax in this
      setting.

PMID- 7500420
TI  - Management of a traumatic pulmonary pseudocyst using high-frequency oscillatory
      ventilation.
AB  - High-frequency ventilation is indicated when acute hypoxemic respiratory failure
      is associated with an ongoing air leak. This report describes the successful use
      of high-frequency oscillatory ventilation in a child with pulmonary contusions
      and traumatic pulmonary pseudocysts who experienced severe air leak syndrome on
      conventional mechanical ventilation.

PMID- 7500421
TI  - Early repair of traumatic ventricular septal defect and mitral valve
      regurgitation.
AB  - Traumatic ventricular septal defect with valvular injury is an uncommon blunt
      trauma. It may develop either immediately or be delayed, but it should be
      corrected electively. With hemodynamic instability and cardiopulmonary
      deterioration, however, early repair is necessary as a lifesaving procedure. Two
      dimensional echocardiography and Doppler color flow mapping are very important
      for rapid detection in patients who are critically injured. This is a case report
      of the successful repair of ventricular septal defect and posterior leaflet
      disruption of mitral valve right after blunt trauma.

PMID- 7500422
TI  - "Splint-top" fracture of the forearm: a description of an in-line skating injury
      associated with the use of protective wrist splints.
AB  - Upper extremity injuries are commonly seen in the sport of in-line skating. The
      use of protective equipment, including wrist splints, has been advocated as a
      means to decrease both the incidence and severity of upper extremity injuries in
      this sport. We report on four cases of open forearm fractures in the in-line
      skaters that occurred adjacent to the proximal border of the wrist splints. The
      unusual nature of these injuries and the location of the fractures in relation to
      the location of the splints suggest that the two may be mechanistically related.
      The splint and distal forearm may act as a single unit to convert the impact from
      the level of the wrist to a torque moment, with the fulcrum located at the
      proximal border of the splint. The energy from the fall is then dissipated by the
      fracturing of the forearm bones at this level. These cases suggest that the use
      of wrist splints may be associated with their own specific set of injury
      patterns.

PMID- 7500423
TI  - Traumatic dislocation of the tibialis posterior tendon: a new surgical procedure
      to obtain a strong reconstruction.
AB  - Traumatic dislocation of the tibialis posterior tendon (TPT) is an uncommon
      condition. The diagnosis is difficult and may be delayed, impairing the activity
      level. The authors present a case, wherein the diagnosis was clinical, supported
      by magnetic resonance imaging. Treatment was surgical; reconstruction of the
      retinaculum was performed with a medial slip of the Achilles tendon that was
      detached proximally and attached to the medial malleolus. A full functional
      recovery to a highly competitive activity was obtained after 12 weeks.

PMID- 7500424
TI  - Late results of split-grafted penoscrotal avulsion injuries.
AB  - Penoscrotal avulsion injuries are rare surgical emergencies. The best treatment
      for penile avulsions is split skin graft, although late results of split-grafted
      scrotal avulsions are not superior. Scrotal skin avulsions require additional
      judgment for the treatment, because there are several available treatment
      options. Scrotal skin remnants must be used to cover whenever possible.

PMID- 7500425
TI  - A fatality associated with the deployment of an automobile airbag.
AB  - Airbags have become an increasingly accepted automobile safety feature that can
      reduce the morbidity and mortality associated with motor vehicle collisions. We
      present the following case report of an unusual fatality with multiple internal
      injuries from a minor mechanism motor vehicle collision. The cause of injuries
      was determined to be secondary to the deployment of a driver's side airbag
      without the concomitant use of a lap-shoulder belt.

PMID- 7500426
TI  - Doppler sonographic studies on the ophthalmic and central retinal arteries in the
      gravid woman.
AB  - The aim of this study was to establish normative data as gestation advances for
      pulsed Doppler evaluation of both the ophthalmic artery and the central retinal
      artery. After measuring intraocular pressure and blood pressure, pulsed Doppler
      ultrasonographic examination was performed on the ophthalmic and central retinal
      arteries in both eyes of 125 normal pregnant women. Nomograms, with 95%
      prediction intervals, have been generated for the Doppler indices, reflecting
      blood flow in both the ophthalmic and the central retinal arteries. The use of
      this technique in the management of pregnancy induced hypertension can now be
      better evaluated.

PMID- 7500427
TI  - Focal hypoechoic regions in the liver at the porta hepatis: prevalence in
      ambulatory patients.
AB  - We prospectively performed hepatic sonography on 534 ambulatory patients to
      determine the prevalence of one or more focal hypoechoic areas in the liver
      adjacent to the gallbladder or portal vein. Obese patients were identified via
      the body mass index calculated from height and weight data. Among our patients,
      5.3% demonstrated at least one focal hypoechoic area. Of the patients with
      positive results, 65.4% were obese, compared to 42.8% of the remainder of the
      patients (P = 0.016). Focal hypoechoic regions in the liver at the porta hepatis
      may be more prevalent than previously believed and are more prevalent in obese
      than nonobese patients.

PMID- 7500428
TI  - Ultrasonographically guided manual compression of femoral artery injuries.
AB  - To determine the success and complication rates of ultrasonographically guided
      manual compression in patients with femoral arterial injuries after femoral
      arterial catheterization, we performed 53 sonographically guided compression
      repairs in 51 patients. Ultrasonographically guided compression repair was
      performed on 40 pseudoaneurysms in non-anticoagulated patients, seven
      pseudoaneurysms in anticoagulated patients, four arteriovenous fistulas on non
      anticoagulated patients, and one pseudoaneurysm combined with an arteriovenous
      fistula. One pseudoaneurysm underwent two separate ultrasonographically guided
      compression repairs: once when the patient was anticoagulated and once after
      anticoagulants were withheld. Ultrasonographically guided compression repair was
      successful in 37 of 48 pseudoaneurysms (77%). Of the 40 pseudoaneurysms in non
      anticoagulated patients, ultrasonographically guided compression repair was
      successful in 36 (90%). This repair technique failed in all seven pseudoaneurysms
      in anticoagulated patients. Ultrasonographically guided compression repair was
      successful in 13 of 16 (81%) multilobulated pseudoaneurysms but failed in all
      arteriovenous fistulas and the one case of pseudoaneurysm combined with an
      arteriovenous fistula. Ultrasonographically guided compression repair is a safe
      and effective alternative to surgery for the repair of pseudoaneurysms, including
      multilobulated pseudoaneurysms. The procedure does not appear to be effective in
      the anticoagulated patient or in patients with an arteriovenous fistula.

PMID- 7500429
TI  - Combined estrogen-progesterone therapy.

PMID- 7500430
TI  - Echogenicity of fibroadenoma and carcinoma of the breast. Quantitative comparison
      using gain-assisted densitometric evaluation of sonograms.
AB  - The purpose of this study was to evaluate the role of ultrasonography in
      differentiation between the echogenic characteristics of carcinoma and those of
      fibroadenoma of the breast. Two mathematical transformations of the measured
      density on a sonographic image of the breast lesion at three different system
      gain settings were used in cases of carcinoma (n = 16) and fibroadenoma (n = 31)
      to provide standardized density values. A significant correlation was found
      between the tumor and the surrounding tissue densities in both carcinomas (r =
      0.77, P = 0.0004) and fibroadenomas (r = 0.79, P < 0.000001. The mean
      standardized density of the tumor was significantly higher (P < 0.0001) than the
      surrounding tissue in both carcinomas (2.03 +/- 0.64 D versus 1.23 +/- 0.38 D)
      and fibroadenomas (2.09 +/- 0.48 D versus 1.33 +/- 0.3 D). However, the
      differences between density values of carcinoma and fibroadenomas were not
      significantly different. The data suggest that it may not be possible to
      differentiate breast carcinoma and fibroadenomas on the basis of the echogenicity
      of solid breast masses.

PMID- 7500431
TI  - Sonographic assessment of infrarenal inferior vena caval dimensions.
AB  - The dimensions of the infrarenal inferior vena cava during quiet respiration,
      single leg lifting, and breath-holding were assessed using sonography in 156
      patients. Sonographic assessment of infrarenal inferior vena caval dimensions was
      feasible in 69% of patients. Measurements during breath-holding were
      significantly greater than during quiet respiration (P < 0.001) and leg lifting
      (P < 0.005), although in approximately one quarter of the patients the mean
      calculated diameter was greatest during quiet respiration. we conclude that
      sonographic assessment of infrarenal inferior vena caval dimensions is feasible,
      but it should be performed during quiet respiration and breath-holding to allow
      for variation with different respiratory maneuvers.

PMID- 7500432
TI  - Importance of dynamic assessment of the soft tissues in the sonographic diagnosis
      of echogenic superficial abscesses.
AB  - Superficial abscesses evaluated by ultrasonography may occasionally be isoechoic
      relative to the surrounding inflamed tissues and without mass effect, preventing
      diagnosis by morphologic criteria alone. We present a simple and effective method
      to detect such abscesses. In three cases, gentle repetitive pressure of the
      inflamed tissue revealed the liquefied nature of abscesses that otherwise would
      have been overlooked.

PMID- 7500433
TI  - The ultrasonographic appearance and outcome for fetuses with masses distorting
      the fetal face.
AB  - Our objective was to determine the appearance, cause, and outcome of fetal face
      masses diagnosed antenatally by ultrasonography. Over a 6 year period, 10
      consecutive fetuses with facial masses were identified. Ultrasonographic
      findings, neonatal pathologic findings, and outcome data were correlated. Four
      (40%) of the 10 fetuses died, including one with a palatal teratoma associated
      with a Dandy-Walker malformation and three with intracranial teratomas--one of
      which was associated with hydrops fetalis. Among the survivors, one fetus had a
      dacryocystocele that was managed conservatively and one had drainage of a
      salivary gland cyst. The remaining four neonates had successful excision of their
      tumors in the neonatal period and survived; these infants had a nasal teratoma, a
      thyroid teratoma, a gingival granular cell tumor, and a scalp hemangioma. Four of
      the 10 pregnancies had associated polyhydramnios, three of which ended in
      stillbirth or neonatal death. In conclusion, 40% of the fetuses with antenatal
      diagnosis of fetal facial masses did not survive. If those with intracranial
      teratomas are removed from this group, one of seven (14%) fetuses with
      extracranial masses died. The intracranial teratomas were uniformly fatal.
      Polyhydramnios was associated with poor outcome.

PMID- 7500434
TI  - Sonography in the postoperative evaluation of laparoscopic inguinal hernia
      repair.
AB  - We evaluated the use of sonography as a means of assessing hernial occlusion and
      possible postoperative changes such as hematomas or seromas in the inguinal and
      scrotal regions after 1139 laparoscopic repairs of hernias between August 1992
      and November 1994. Changes after laparoscopic hernia repair were found in 307
      patients (27%). Hematomas or seromas were seen in 132 patients, protrusion of the
      prosthetic mesh in 17, mesh infection in two, and small bowel entrapment in an
      insufficient peritoneal suture in two. Recurrences were diagnosed correctly in
      six patients, mobile preperitoneal lipomas in five. Sonography is useful in the
      evaluation of complications after laparoscopic hernia repair, including recurrent
      hernia. In the absence of symptoms, sonography is not indicated.

PMID- 7500435
TI  - Sonohysterography for ultrasonographic evaluation of tamoxifen-associated cystic
      thickened endometrium.
AB  - Most menopausal patients with breast cancer receive tamoxifen therapy. In these
      patients, TVS may show thickened, irregular cystic endometria. For better
      visualization of these patients' uterine cavities, we performed transvaginal
      sonohysterography. During vaginal ultrasonography, sterile saline was introduced
      by transcervical 8 French Foley catheter into the uterine cavity of 20 women who
      were referred with tamoxifen-associated cystic thickened endometria. In eight
      women, transvaginal sonohysterography provided the means to diagnose occult, free
      floating endometrial polyps, whereas in 12 women, the fluid contrast augmented
      the diagnosis of an irregular cystic endometrial-myometrial junction. All 20
      patients underwent diagnostic hysteroscopy: eight polyps, none of which were
      malignant, were confirmed and removed by hysteroscopic resection. Of the
      remaining 12 patients with an irregular endometrial-myometrial junction,
      endometrial curettage showed no significant pathologic findings. Transvaginal
      sonohysterography seems to enhance the differentiation between endometrial polyps
      that should be resected by operative hysteroscopy and an abnormal endometrial
      myometrial junction that may benefit from biopsy sampling only.

PMID- 7500436
TI  - Lipomatous uterine masses: potential to mimic ovarian dermoids on endovaginal
      sonography.
AB  - Lipomatous uterine masses are uncommon hyperechoic pelvic neoplasms composed
      partly of adipose tissue. Because of the high level of echogenicity, these
      uterine masses can produce produce a sonographic appearance strikingly similar to
      the "dermoid plug" that is considered characteristic of benign cystic teratomas.
      The key to distinguishing the two tumors is to ascertain the parent organ: the
      lipomatous uterine mass should clearly originate from the myometrium. In our
      experience, however, the origin of some echogenic pelvic masses can be difficult
      to determine, particularly from the endovaginal perspective. This report
      describes the transabdominal and endovaginal ultrasonographic findings in three
      patients with lipomatous uterine masses for whom the endovaginal perspective
      alone, without supplemental transabdominal views, would have resulted in
      misdiagnosis.

PMID- 7500437
TI  - Sonographic presentation of unilateral hematometra: report of two cases.

PMID- 7500438
TI  - Sonographic detection of the pelvic peritoneal fluid.

PMID- 7500439
TI  - Reversible portal venous gas in hypertrophic pyloric stenosis: detection by
      ultrasound.

PMID- 7500440
TI  - False-positive carotid compression with transcranial Doppler examination.

PMID- 7500441
TI  - Sonographic diagnosis of accessory soleus muscle mimicking a soft tissue tumor.

PMID- 7500442
TI  - Absent thoracolumbar spine: prenatal sonography of a new lethal skeletal anomaly.

PMID- 7500443
TI  - Estrogens in the treatment of prostate cancer.
AB  - PURPOSE: The history, mechanisms of action, efficacy and complications of
      estrogen therapy for prostate cancer are reviewed, and the current and future
      roles of estrogens in the treatment of prostate cancer are addressed. MATERIALS
      AND METHODS: An extensive review of the literature was done. RESULTS: Estrogens
      are effective in the treatment of advanced prostate cancer. High dose oral
      estrogens are associated with an increased risk of cardiovascular death. A dose
      of 1 mg. diethylstilbestrol daily is not associated with an increased risk of
      cardiovascular death. Estrogens are associated with other toxicities. Parenteral
      estrogens may not have the risk of cardiovascular death that is ascribed to oral
      estrogens. Estrogens have not been adequately compared to the combined androgen
      blockade regimen. CONCLUSIONS: A 1 mg. dose of diethylstilbestrol remains a
      medial alternative to bilateral orchiectomy in the treatment of advanced prostate
      cancer. Doses of 3 mg. diethylstilbestrol or more have a prohibitively high risk
      of cardiovascular death. Further studies comparing the efficacy, complications
      and cost of regimens containing oral estrogens or parenteral estrogens with
      agents that increase efficacy (for example antiandrogens) and decrease toxicity
      (for example anticoagulants) to results of other regimens, such as combined
      androgen blockade, should be done to determine if an estrogen-containing regimen
      could lower the cost of treating advanced prostate cancer.

PMID- 7500444
TI  - Sentinel lymph node dissection for penile carcinoma: the M. D. Anderson Cancer
      Center experience.
AB  - PURPOSE: We determined whether an extended sentinel lymph node dissection is
      effective for staging penile squamous carcinoma associated with clinically
      negative inguinal lymph nodes. MATERIALS AND METHODS: A retrospective review was
      done of 20 consecutive patients who underwent extended sentinel lymph node
      dissection between 1985 and 1994. RESULTS: Of the patients 14 underwent bilateral
      extended sentinel lymph node dissection, and 6 underwent ipsilateral extended
      sentinel lymph node dissection plus contralateral inguinal or ilioinguinal
      lymphadenectomy. All lymph nodes included in the extended sentinel node
      dissection were negative for metastases. Five patients had inguinal metastases at
      a median of 10 months (range 3 to 21) after negative extended sentinel lymph node
      dissection. CONCLUSIONS: Although it is a more extensive procedure than sentinel
      lymph node biopsy, extended sentinel lymph node dissection is still associated
      with a significant false-negative rate (25%). Thus, its routine use can no longer
      be recommended.

PMID- 7500445
TI  - Clinical, hormonal and pathological findings in a comparative study of
      adrenocortical neoplasms in childhood and adulthood.
AB  - PURPOSE: We reviewed clinical and laboratory findings in 6 male and 32 female
      patients with functional adrenocortical neoplasms, and compared pediatric and
      adult data. MATERIALS AND METHODS: Hormonal measurements were performed by
      radioimmunoassay, histological analysis was based on Weiss criteria and staging
      was done according to previously established guidelines. RESULTS: Children had a
      higher incidence of virilization (72%), whereas in adults the predominant feature
      was Cushing's syndrome (60%). A high testosterone level was the most common
      finding in adults and children with virilization followed by high
      dehydroepiandrosterone sulfate, androstenedione and dehydroepiandrosterone
      levels. High 11-deoxycortisol levels were frequently associated with tumor
      recurrence. Cortisol suppression after dexamethasone was altered in 93% of
      patients with virilization and no clinical features, suggesting autonomous
      cortisol secretion. CONCLUSIONS: No statistically significant relation was noted
      between tumor weight and prognosis but there was a negative correlation between
      patient age and prognosis since children had a more favorable followup than
      adults. Mixed features in both groups resulted in the worst prognosis. A Weiss
      criteria grade IV or greater correlated well with a poor prognosis in adults but
      not children, while staging was more reliable in children.

PMID- 7500446
TI  - Prevalence of microscopic lesions in grossly normal renal parenchyma from
      patients with von Hippel-Lindau disease, sporadic renal cell carcinoma and no
      renal disease: clinical implications.
AB  - PURPOSE: We sought to describe the earliest renal lesions in patients with von
      Hippel-Lindau disease to gain insight into the genesis of renal neoplasms in this
      condition. MATERIALS AND METHODS: Grossly normal renal parenchyma from von Hippel
      Lindau disease patients was examined microscopically and compared to findings in
      similar tissues obtained from patients with sporadic renal cancer and from
      autopsy subjects with no renal disease. RESULTS: Microscopic renal cystic and
      solid neoplasms containing only clear cell cytological features were found in
      patients with von Hippel-Lindau disease. Benign cysts with clear cell cytological
      features were found only in patients with von Hippel-Lindau disease. Benign cysts
      lined by cuboidal cells with eosinophilic cytoplasm, similar to renal tubular
      cells, were present only in patients with renal cancer. The extrapolated number
      of clear cell lesions in an average kidney with von Hippel-Lindau disease was
      estimated as 1,100 cysts (benign or atypical) with clear cell lining and 600
      clear cell neoplasms. CONCLUSIONS: These findings support the hypothesis that
      abnormalities in the von Hippel-Lindau gene in a kidney results in the
      cytological cell type of clear cell renal cancer as the initial product of
      cellular transformation.

PMID- 7500447
TI  - Nephron sparing surgery for renal cell carcinoma in von Hippel-Lindau disease.
AB  - PURPOSE: We evaluated the technical feasibility and followup outcomes of a
      nephron sparing operation for localized renal cell carcinoma and von Hippel
      Lindau disease. MATERIALS AND METHODS: Our 5 patients underwent initial nephron
      sparing surgery followed by serial computerized tomography. RESULTS: All but 1
      renal lesion was resected in 9 initial nephron sparing operations. Postoperative
      computerized tomography revealed 35 lesions of which 8 had enlarged. Four
      patients underwent secondary renal surgery and adequate renal function was
      preserved. CONCLUSIONS: Even with the high risk of local recurrence nephron
      sparing surgery is an appropriate approach for these patients.

PMID- 7500448
TI  - Economic impact of urolithiasis in the United States.
AB  - PURPOSE: We determined the economic costs to individuals in 1993 for the
      evaluation and treatment of upper urinary tract calculi. MATERIALS AND METHODS:
      Hospital discharge statistics, prevalence data for urolithiasis and the relative
      frequency of surgical treatments from Civilian Health and Medical Program of the
      Uniformed Services claims data were assessed. RESULTS: The total charges for
      evaluation, hospitalization and treatment were estimated to be $1.23 billion per
      year. Professional charges for those who were hospitalized were estimated to be
      $183 million. Outpatient evaluation of urolithiasis was expected to cost $278
      million. Indirect costs for lost wages were estimated to be $139 million.
      CONCLUSIONS: The total annual cost for urolithiasis in the United States is
      estimated to be $1.83 billion.

PMID- 7500449
TI  - Fibrous coagulum: a new cause of retained fragments following extracorporeal
      shock wave lithotripsy.
AB  - PURPOSE: A previously unrecognized cause of retained fragments following
      extracorporeal shock wave therapy is identified. MATERIALS AND METHODS: Nine
      patients referred for percutaneous stone extraction following failure of multiple
      shock wave lithotripsy treatments had retained fragments embedded in soft tissue.
      The stones were evaluated by chemical analysis and the tissue was evaluated
      histologically. RESULTS: All stones contained calcium and histopathology
      confirmed the presence of fibrous tissue. Radiographs were unable to predict the
      presence of the substance preoperatively. CONCLUSIONS: We identified fibrous
      coagulum as a cause of retained fragments following shock wave lithotripsy. The
      material is soft tissue and cannot be ablated by further shock wave lithotripsy.
      These findings confirm that repeated shock wave lithotripsy is contraindicated,
      since stone fragmentation and passage may be inhibited by fibrous coagulum.

PMID- 7500450
TI  - Early results with split-cuff nipple ureteral reimplants in urinary diversion.
AB  - PURPOSE: A split-cuff nipple technique was developed for ureteral reimplantation
      in urinary diversion. MATERIALS AND METHODS: Ureteroenteric anastomosis was
      performed with a uniform split-cuff nipple technique in 46 ureters of 24 adult
      patients undergoing various forms of conduit or continent urinary diversion. The
      outcome of 42 reimplants in 22 patients (mean followup 22.5 months, minimum 10)
      was analyzed. The technique is described in detail. RESULTS: Reflux was prevented
      in 97.6% and 95% of cases at initial and 2-year followup, respectively. Neither
      anastomotic leakage nor obstruction occurred. There were 2 episodes of
      pyelonephritis in the early postoperative period. Results are compared with those
      in the literature of ureteroenteric anastomoses in general and of various split
      cuff nipple techniques. CONCLUSIONS: The technique is easy to perform. Favorable
      early results warrant continued use of the procedure. Long-term followup in a
      larger number of patients is indicated.

PMID- 7500451
TI  - Continuous versus intermittent bladder irrigation of amphotericin B for the
      treatment of candiduria.
AB  - PURPOSE: The efficacy of continuous versus intermittent bladder irrigation with
      amphotericin B in the treatment of candiduria was compared. MATERIALS AND
      METHODS: A prospective, randomized and comparative pilot study was done on 20
      patients. Continuous bladder irrigation with 50 mg./l. amphotericin B infused
      during 24 hours for 2 days was compared to 3 intermittent bladder irrigations of
      10 mg./100 ml. amphotericin B in 1 day. Urine cultures were obtained 72 hours
      after treatment. RESULTS: The organism was eradicated in 8 patients (80%) who
      received continuous irrigation and 3 (30%) who received intermittent irrigation
      (p = 0.035). CONCLUSIONS: Continuous amphotericin B bladder irrigation was
      superior in terms of efficacy, ease of administration and patient comfort.

PMID- 7500452
TI  - Interstitial cystitis in The Netherlands: prevalence, diagnostic criteria and
      therapeutic preferences.
AB  - PURPOSE: We determine the prevalence of interstitial cystitis in The Netherlands,
      and analyze the most common diagnostic and therapeutic approaches among Dutch
      urologists. MATERIALS AND METHODS: A questionnaire was completed by urologists
      and analyzed with the help of a statistical computer program. RESULTS: The
      prevalence of interstitial cystitis was calculated to be 8 to 16/100,000 female
      patients. Pathology of bladder biopsies and the presence of mast cells were the
      main diagnostic criteria. Dimethyl sulfoxide instillations, bladder
      hydrodistension and surgery were the most frequently applied therapies.
      CONCLUSIONS: The prevalence of interstitial cystitis in The Netherlands is in
      line with that of other reports from Europe but low compared to the United States
      findings. The importance of pathology and the presence of mast cells in the
      diagnosis, as well as less awareness might contribute to this difference.

PMID- 7500453
TI  - Absence of neuropathic pelvic pain and favorable psychological profile in the
      surgical selection of patients with disabling interstitial cystitis.
AB  - PURPOSE: We evaluated the results among patients with disabling interstitial
      cystitis treated by cystectomy, urethrectomy and creation of a continent colonic
      urinary reservoir (the Florida pouch). The value of psychological evaluation and
      pain localization techniques, as well as the use of a team approach in the
      evaluation of these patients were assessed. MATERIALS AND METHODS: The 20 women
      and 2 men who underwent surgery for disabling interstitial cystitis ranged from
      31 to 75 years old (mean age 48). The duration of symptoms ranged from 2 to 14
      years (mean 7). All patients had undergone multiple prior therapies, including
      vesical hydrodistension, instillations, laser treatments, and use of
      tranquilizers and a variety of pain medications. Patients underwent a clinical,
      cystoscopic (with bladder biopsies) and urodynamic evaluation as well as
      examination by a gynecologist with expertise in vaginal ultrasonography. The last
      5 patients underwent psychological evaluation and pain localization techniques.
      RESULTS: Among the clinical parameters, the presence of a small capacity bladder
      with the patient under anesthesia (less than 400 cc) was associated with the best
      surgical results. Among 11 patients evaluated only clinically success was
      achieved in 64%, while all 5 (100%) who also underwent pain localization
      techniques and psychological evaluation had a successful outcome postoperatively.
      The overall surgical success rate in the 22 patients was 73%. Two patients
      undergoing psychological evaluation and pain localization techniques were not
      considered to be surgical candidates. Among 7 surgical failures 4 patients
      underwent postoperative psychological evaluation and pain localization
      techniques, and they would not have been considered candidates for surgery with
      the new parameters. CONCLUSIONS: A team approach is essential in the evaluation
      of these patients. Following the initial selection of patients who had a small
      bladder capacity while under anesthesia, psychological evaluation and pain
      localizing techniques may assist surgeons in selecting those who would benefit
      from a radical operation.

PMID- 7500454
TI  - Interstitial cystitis revisited.

PMID- 7500455
TI  - Rationale and technique of nerve sparing radical cystectomy before an orthotopic
      neobladder procedure in women.
AB  - PURPOSE: We developed refinements in the technique of cystectomy and subsequent
      intestine to urethra anastomosis to improve postoperative results in women
      undergoing anterior exenteration and creation of an orthotopic neobladder to the
      urethra. MATERIALS AND METHODS: Anatomical dissection and microdissection studies
      were performed on formalin-carbol fixed adult cadavers and correlated with
      previous anatomical and clinical findings. The resulting surgical variations were
      performed in 5 carefully selected women undergoing lower urinary tract
      reconstruction. RESULTS: Optimal postoperative results in regard to continence
      and voiding without compromising oncological outcome may be obtained by
      preserving the entire lateral vaginal walls, performing nerve sparing dissection
      of the bladder neck and proximal urethra, removing 1 cm. proximal urethra en bloc
      with the cystectomy specimen and using additional attachments of the anastomosed
      intestinal pouch to surrounding pelvic structures. Patients achieved day and
      night continence after 6 months, mean pouch volume was 580 cc (range 450 to 750)
      and residual volumes ranged from 0 to 150 cc. No tumor recurred after 6 to 17
      months. CONCLUSIONS: Refinements in the technique of radical cystectomy and
      orthotopic neobladder to the urethra in women may improve continence and
      spontaneous voiding without compromising surgical oncological outcome, and they
      further justify orthotopic diversion in select women with bladder cancer.

PMID- 7500456
TI  - Alternating mitomycin C and bacillus Calmette-Guerin instillation therapy for
      carcinoma in situ of the bladder. The Finnbladder Group.
AB  - PURPOSE: Our aim was to prove if alternating chemotherapeutic and
      immunotherapeutic instillations improved efficacy and reduced toxicity in
      patients with carcinoma in situ of the bladder. MATERIALS AND METHODS: Of 68
      carcinoma in situ patients randomly treated with instillations 40 received
      mitomycin C and 28 received mitomycin C and Pasteur bacillus Calmette-Guerin
      (BCG) in alternating courses. Mean followup was 33 months. RESULTS: The complete
      response rates with mitomycin C and mitomycin C/BCG were 45% and 71% at 3 months,
      59% and 82% at 12 months, and 47% and 74% at 24 months, respectively (p = 0.041).
      The disease-free interval showed the superiority of alternating therapy (p =
      0.043). Recurrence rates during the instillation period were 1.834 with mitomycin
      C and 0.922 with mitomycin C/BCG (p = 0.013). No remarkable side effects
      developed in the alternating group. CONCLUSIONS: Therapy of carcinoma in situ
      with alternating mitomycin C and BCG is more effective than mitomycin C alone.
      Compared to BCG monotherapy only few side effects occur.

PMID- 7500457
TI  - Bacillus Calmette-Guerin in the treatment of stage T1 grade 3 transitional cell
      carcinoma of the bladder: long-term results.
AB  - PURPOSE: We performed a retrospective long-term study to evaluate the results of
      immunotherapy in the treatment of high grade superficial bladder tumors.
      MATERIALS AND METHODS: Between 1981 and 1993, 593 patients with superficial
      transitional cell carcinoma of the bladder underwent transurethral resection. Of
      64 patients with stage T1 grade 3 disease 50 received intravesical bacillus
      Calmette-Guerin after transurethral resection of all visible tumor. RESULTS: At a
      median followup of 42 months (range 12 to 112) 36 patients (72%) are disease-free
      and have not required further treatment. Superficial recurrence was noted in 8
      patients (16%). Disease progressed in 6 patients (12%), including 5 with locally
      invasive and 1 with metastatic disease. Cystectomy was performed for progression
      in 4 patients and for recurrent stage T1 grade 3 disease in 1. There was 1
      disease related death (2%). The overall survival rate is 94%. CONCLUSIONS:
      Intravesical bacillus Calmette-Guerin appears to be the most effective
      conservative treatment for patients with stage T1 grade 3 bladder cancer.

PMID- 7500458
TI  - The relationship of local control to distant metastasis in muscle invasive
      bladder cancer.
AB  - PURPOSE: We examined the relationship of local failure to distant metastasis in
      patients with muscle invasive bladder cancer. MATERIALS AND METHODS: This
      retrospective review included 240 patients treated with radical cystectomy with
      or without multiagent chemotherapy at our institution between 1984 and 1990 for
      clinical stage T2 to T4 transitional cell carcinoma of the bladder. The
      distribution of patients by clinical stage was 89 T2, 77 T3a, 51 T3b and 23 T4.
      Median followup was 55 months. RESULTS: The actuarial 5-year local control,
      freedom from distant metastasis and overall survival rates were 80%, 68% and 52%,
      respectively. There was a profoundly significant relationship between local
      failure and distant metastasis with distant metastasis in 56% of those with local
      failure. The actuarial 5-year freedom from distant metastasis rate for those with
      local control was 77% compared to 29% for those with local failure (p < 0.0001,
      log rank test). This relationship held when the group was subdivided by stage and
      when only cases of complete cystectomy were analyzed. The significance of this
      finding in light of the possible contribution of potential prognostic factors was
      examined. Univariate analyses revealed late clinical stage, abnormal pretreatment
      serum creatinine levels, the administration of chemotherapy, late pathological
      stage and lymph node involvement to correlate significantly with distant
      metastasis rates. Multivariate analyses using Cox proportional hazards models
      with freedom from distant metastasis as the end point revealed pathological
      stage, local failure and lymph node involvement to be the only significant
      covariates. CONCLUSIONS: Since local failure highly correlated with distant
      failure, treatment planning to optimize local control should be of foremost
      concern for those at high risk of failure by this mode (for example patients with
      T3b/4 disease). New treatment strategies, such as the use of preoperative
      radiotherapy as an adjunct to chemotherapy and radical surgery, should be
      considered in this high risk population.

PMID- 7500459
TI  - Early and late long-term effects of vasectomy on serum testosterone,
      dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels.
AB  - PURPOSE: We investigated whether the association between vasectomy and prostate
      cancer has a hormonal basis. MATERIALS AND METHODS: We examined serum
      testosterone, dihydrotestosterone, luteinizing hormone and follicle-stimulating
      hormone levels by radioimmunoassay on 91 pairs of men who did and did not undergo
      vasectomy. RESULTS: Men who underwent vasectomy 10 to 19 years previously had
      higher dihydrotestosterone levels than age matched controls. In men who underwent
      vasectomy 20 years or more ago testosterone was higher than in corresponding
      controls. No statistically significant difference in luteinizing hormone and
      follicle-stimulating hormone levels was noted between the men who had had
      vasectomy and controls. CONCLUSIONS: Our results indirectly support the
      hypothesis that there is an elevated risk of prostate cancer among men who
      underwent vasectomy 20 or more years previously.

PMID- 7500460
TI  - Patency following microsurgical vasoepididymostomy and vasovasostomy: temporal
      considerations.
AB  - PURPOSE: We evaluate the temporal parameters of patency following
      vasoepididymostomy and vasovasostomy. MATERIALS AND METHODS: A series of
      consecutive and concurrent vasoepididymostomies (100) and vasovasostomies (100)
      performed by a single surgeon (M. G.) was reviewed. RESULTS: Patency rates
      following vasoepididymostomy and vasovasostomy were 65% and 99%, respectively (p
      < 0.001). Motile sperm were observed at a mean of 5.8 +/- 0.8 months (standard
      error) following vasoepididymostomy and 2.1 +/- 0.2 months following
      vasovasostomy (p < 0.01). Late failure rates were 21% for vasoepididymostomy and
      12% for vasovasostomy. Pregnancy rates following vasoepididymostomy and
      vasovasostomy were 21% and 52%, respectively. CONCLUSIONS: Patency is rapid
      following vasovasostomy but requires 12 or more months following
      vasoepididymostomy. Intervention for azoospermia is appropriate 6 months after
      vasovasostomy and 1 year after vasoepididymostomy. Intraoperative
      cryopreservation of sperm in men undergoing vasoepididymostomy and
      postoperatively in all men with motile sperm will maximize fertility options.

PMID- 7500461
TI  - Intracytoplasmic testicular sperm injection: an effective treatment for otherwise
      intractable obstructive azoospermia.
AB  - PURPOSE: We evaluated the efficacy of intracytoplasmic sperm injection with
      testicular spermatozoa. MATERIALS AND METHODS: Intracytoplasmic sperm injection
      was performed with spermatozoa obtained from testicular biopsy specimens in 15
      patients with obstructive azoospermia, in whom standard microsurgical procedures
      were not feasible or had previously failed. RESULTS: Fertilization was achieved
      in 14 of 15 cycles. Mean fertilization rate per cycle was 63.6%. Four clinical
      pregnancies occurred, for a pregnancy rate of 26.7% per started cycle and 28.6%
      per transfer. CONCLUSIONS: Intracytoplasmic testicular sperm injection is
      followed by high fertilization rates, and offers the chance of a pregnancy to
      otherwise intractably infertile couples with obstructive azoospermia.

PMID- 7500462
TI  - New techniques for sperm acquisition and use--a cause for excitement and concern.

PMID- 7500463
TI  - Evaluation of fluid absorption during laser prostatectomy by breath ethanol
      techniques.
AB  - PURPOSE: Laser prostatectomy has evolved as a less invasive method of relieving
      bladder outlet obstruction due to prostatic enlargement. The elimination of
      adenomatous tissue by laser induced coagulation necrosis theoretically avoids the
      sequelae of fluid absorption noted during traditional transurethral resection of
      the prostate. However, to our knowledge no accurate determination of fluid
      absorption during laser prostatectomy has been performed to date. MATERIALS AND
      METHODS: A technique previously described to determine the amount of irrigant
      absorbed during transurethral resection of the prostate measures breath ethanol
      levels using a standard alcohol breath analyzer during the procedure after a
      predetermined amount of ethanol is added to the irrigant fluid. This method was
      used in 4 men undergoing laser prostatectomy. RESULTS: All 4 subjects had ethanol
      levels of 0 throughout the operation, indicating that little or no irrigant fluid
      was absorbed. CONCLUSIONS: We demonstrated in a quantitative manner that fluid
      absorption during laser prostatectomy is almost nil and patients are, indeed, at
      no risk for the transurethral resection syndrome.

PMID- 7500464
TI  - A randomized study comparing visual laser ablation and transurethral evaporation
      of prostate in the management of benign prostatic hyperplasia.
AB  - PURPOSE: We evaluated the safety, efficacy, failure and complications of 2
      techniques of laser prostatectomy for benign prostatic hyperplasia (BPH):
      transurethral evaporation of the prostate (evaporation) versus visual laser
      ablation of the prostate (coagulation) in a randomized trial. MATERIALS AND
      METHODS: A total of 64 consecutive patients with symptomatic BPH was randomized
      to undergo evaporation (32) or coagulation (32). American Urological Association
      symptom score, peak urinary flow rate and post-void residual urine volume were
      measured at baseline, and at 1, 3, 6 and 12 months. Other parameters evaluated
      included prostate volume by transrectal ultrasound, total laser energy per
      patient and per cc volume of the prostate, number of laser fibers per prostate,
      duration of catheterization and hospitalization, need for re-catheterization, and
      failure and complication rates. RESULTS: Our main findings were that patients
      undergoing laser prostatectomy using the coagulation technique (visual laser
      ablation of the prostate) had higher reoperation rates (16% versus 0%, p =
      0.0199) and were 4 times more likely to have prolonged postoperative urinary
      retention (25% versus 6.3%, p = 0.0389), evaporation and coagulation were
      effective at relieving symptoms of prostatism with significant improvement in
      American Urological Association symptom scores and post-void residual urine
      volumes compared to baseline, improvement in peak flow rates was significantly
      greater in patients undergoing evaporation at 1, 3, 6 and 12 months (p < 0.001)
      compared to coagulation, and a significantly greater amount of laser energy was
      required to evaporate a unit volume of prostate tissue compared to coagulation
      (2,251 J./cc versus 1,036 J./cc, p < 0.03). CONCLUSIONS: Between the 2 major
      techniques of laser prostatectomy, transurethral evaporation is associated with
      better results at up to 12 months of followup.

PMID- 7500465
TI  - Biodegradable self-reinforced polyglycolic acid spiral stent in prevention of
      postoperative urinary retention after visual laser ablation of the prostate-laser
      prostatectomy.
AB  - PURPOSE: The efficacy and safety of a new biodegradable (self-reinforced
      polyglycolic acid) spiral stent in securing free voiding despite edema after
      visual laser ablation of the prostate were studied. MATERIALS AND METHODS: A
      biodegradable spiral stent was inserted into the prostatic urethra in 22 patients
      immediately after visual laser ablation of the prostate. Uroflowmetry,
      measurement of residual urine volume, urine culture, cystoscopy and assessment of
      symptomatic improvement were done before, and 1, 3 and 6 months after visual
      laser ablation of the prostate. RESULTS: All 22 patients voided freely on day 1
      or 2 after visual laser ablation of the prostate. However, 4 patients later had
      urinary retention due to a short spiral or too rapid spiral degradation. Half of
      the patients experienced a transient decrease in flow with some obstructive
      symptoms at 3 weeks that lasted 1 to 2 weeks. At 4 weeks all spirals were
      degraded and 3 patients had a positive urine culture. The maximum flow rate
      increased and the residual urine volume decreased significantly concomitantly
      with significant symptomatic improvement. CONCLUSIONS: The self-reinforced
      polyglycolic acid spiral stent can effectively and safely prevent postoperative
      urinary retention after visual laser ablation of the prostate.

PMID- 7500466
TI  - Laser prostatectomy--what we have accomplished and future directions.

PMID- 7500467
TI  - Localization of the alpha 1A-adrenoceptor in the human prostate.
AB  - PURPOSE: We determined the tissue localization of the alpha 1a-adrenoceptor in
      the human prostate. MATERIALS AND METHODS: Autoradiographic localization of the
      alpha 1a-adrenoceptor in the human prostate was determined by performing
      competitive displacement experiments on slide mounted tissue sections using the
      ligand 125iodine-2-(-[4-hydroxyphenyl]-ethyl-aminomethyl)tetralone (125I-Heat),
      and the alpha 1-antagonists WB-4101 (4 x 10(-8) M.) and 5-carboxamido-2,6-diethyl
      1,4-dihydro-3-[N-(3-[4-hydroxy-4-phenylpipe ridin- yl]propyl)]carboxamido-4-(4
      nitrophenyl) (SNAP 5272, 3 x 10(-7) M.). Under these experimental conditions, WB
      4101 and SNAP 5272 are selective alpha 1a/alpha 1d-adrenoceptor and alpha 1a
      adrenoceptor antagonists, respectively. The autoradiographs were quantitatively
      analyzed using a computer image analysis system. RESULTS: Specific 125I-Heat
      binding associated with the epithelium and stroma were independently analyzed. WB
      4101 and SNAP 5272 inhibited 100% of the specific 125I-Heat binding in the
      stroma, suggesting that all of the stromal alpha 1-adrenoceptors are of the alpha
      1a subtype. WB-4101 inhibited none of the specific 125I-Heat binding in the
      epithelium, suggesting that the alpha 1-adrenoceptor in the epithelium is of the
      alpha 1b subtype. SNAP 5272 displaced only 25% of the specific 125I-Heat binding
      in the epithelium, suggesting that a relatively small percentage of the
      epithelial alpha 1-adrenoceptor is of the alpha 1a subtype. CONCLUSIONS: To our
      knowledge, our study represents the first cellular localization of the alpha 1
      adrenoceptor subtypes in the human prostate using highly selective alpha 1
      adrenoceptor antagonists and is consistent with the physiological observation
      that the activity of prostatic smooth muscle is mediated by the alpha 1a
      adrenoceptor.

PMID- 7500468
TI  - Familial aspects of prostate cancer: a case control study.
AB  - PURPOSE: We evaluated the importance of positive family history, age at diagnosis
      and history of vasectomy in predicting the risk for prostate cancer in the
      brothers of prostate cancer patients. MATERIALS AND METHODS: A total of 1,084 men
      with newly diagnosed prostate cancer responded by interview to a family history
      survey, which included detailed information on the diagnosis of any cancer in the
      parents of the proband, diagnosis of prostate cancer in male relatives and age at
      onset of prostate cancer in the proband. A history of vasectomy was also obtained
      from the proband. The control cases consisted of 935 spouses of the probands who
      were administered the same questionnaire in an identical fashion. RESULTS:
      Prostate cancer was not significantly associated with other types of cancer in
      proband parents. The presence of prostate cancer in the father, grandfather or
      uncle of the proband significantly increased the risk of prostate cancer in
      proband brothers. Early age at onset in the proband was also associated with an
      increased risk to the proband brothers. CONCLUSIONS: Men with a family history of
      prostate cancer are at a significantly increased risk for prostate cancer,
      especially if the affected relative had early onset of cancer. Prostate cancer
      does not seem to be associated with a higher incidence of other cancers in family
      members.

PMID- 7500469
TI  - Radical retropubic prostatectomy: limited benefit of autologous blood donation.
AB  - PURPOSE: We determine whether autologous blood donation significantly decreases
      the need for homologous transfusions after radical prostatectomy. MATERIALS AND
      METHODS: The effects of estimated blood loss and autologous donation on the rate
      of homologous transfusions were analyzed in 3 groups of 100 consecutive patients
      treated between 1983 and 1992. RESULTS: Overall, donors were less likely than
      nondonors to receive homologous blood. As median estimated blood loss decreased
      from 1,200 to 800 cc from groups 1 to 3 (p < 0.05), the incidence of nondonors
      requiring homologous blood decreased from 62 to 11% and that of autologous units
      transfused decreased from 96 to 19%. CONCLUSIONS: With decreasing blood loss,
      safe but stringent criteria for transfusion and improved safety of the blood
      supply, autologous donation is an inefficient method to lower the slight risk of
      complications following homologous transfusion during radical prostatectomy.

PMID- 7500470
TI  - Bicalutamide in the treatment of advanced prostatic carcinoma: a phase II
      noncomparative multicenter trial evaluating safety, efficacy and long-term
      endocrine effects of monotherapy.
AB  - PURPOSE: The safety, efficacy and pharmacokinetics of bicalutamide were
      investigated in 150 patients with stage D2 prostate cancer. MATERIALS AND
      METHODS: Patients received 50 mg. bicalutamide daily in an open label multicenter
      North American trial. RESULTS: The objective response rate (modified European
      Organization for Research in Cancer Therapy criteria) was 70%. Of 150 patients 59
      (39%) met prostate specific antigen criteria for partial response, and 88 (59%)
      reached treatment failure end points and withdrew. Extent of disease was a
      significant predictor of response but baseline testosterone was not. Breast pain
      and gynecomastia developed in 76% and 60% of patients, respectively. Mean drug
      plasma concentration was 8,528 +/- 2,928 ng/ml. CONCLUSIONS: Bicalutamide (50
      mg.) daily was well tolerated and efficacious. However, suboptimal effects on
      prostate specific antigen have led to additional trials to evaluate monotherapy
      at higher doses.

PMID- 7500471
TI  - Prostate cancer mortality in patients surviving more than 10 years after
      diagnosis.
AB  - PURPOSE: We investigated the long-term outcome of prostate cancer. MATERIALS AND
      METHODS: Causes of death were examined in 490 patients diagnosed with prostate
      cancer in Goteborg between 1960 and 1979 who survived for longer than 10 years.
      RESULTS: Of the patients 75 were alive and 415 died, including 62% as a direct or
      indirect consequence of prostate cancer. CONCLUSIONS: Early prostate cancer is a
      slow growing but progressive malignant disease that will, if the patient survives
      long enough, kill the host.

PMID- 7500472
TI  - Progression in untreated carcinoma of the prostate metastatic to regional lymph
      nodes (stage t0 to 4,N1 to 3.M0,D1). European Organization for Research and
      Treatment of Cancer Genitourinary Group.
AB  - PURPOSE: We attempt to contribute to the understanding of the natural history of
      prostate cancer metastatic to lymph nodes. MATERIALS AND METHODS: A total of 61
      patients with node-positive prostate cancer was prospectively followed without
      adjuvant treatment for an average of 41 months. The impact of T and P categories,
      grade, tumor volume and prostate specific antigen change on interval to
      progression was studied in a univariate and multivariate analysis. RESULTS:
      Median interval to progression was 18 months, and correlated with grade and
      prostate specific antigen doubling time. Changes in prostatic volume with time
      were not predictive. CONCLUSIONS: Our study provides insight into the natural
      history of node-positive disease and identifies relevant prognostic factors that
      may be used for treatment decisions.

PMID- 7500473
TI  - Prognostic criteria in patients with prostate cancer: correlation with volume
      weighted mean nuclear volume.
AB  - PURPOSE: Grading of malignancy in prostate cancer is based on qualitative,
      morphological examination and suffers from poor reproducibility. On the other
      hand, estimating the volume weighted mean nuclear volume, which was developed by
      Gunderson and Jensen based on a stereological technique, is a simple method with
      high reproducibility. Furthermore, it has been reported that mean nuclear volume
      is remarkably correlated with prognosis of bladder cancer. We compared mean
      nuclear volume to 2 histological grading methods and clinical stage to determine
      the prognosis of prostate cancer using a Cox proportional hazards model.
      MATERIALS AND METHODS: A retrospective, prognostic study of 52 patients with
      prostate cancer diagnosed by transurethral resection of the prostate or needle
      punch biopsy between January 1983 and July 1994 was performed. Unbiased estimates
      of mean nuclear volume were compared to patient age at diagnosis, clinical stage,
      histological grading according to the World Health Organization (WHO)
      classification and Gleason score of the prognostic value. RESULTS: Univariate
      analysis revealed that estimates of mean nuclear volume (p = 0.0011), clinical
      stage (p = 0.0014) and WHO classification (p = 0.0010) correlated significantly
      with progression-free survival, and that clinical stage (p = 0.0005) and
      estimates of mean nuclear volume (p = 0.0049) correlated significantly with
      disease-specific survival of patients with prostate cancer. However, multivariate
      analysis revealed that only estimates of mean nuclear volume and clinical stage
      were the 2 most powerful independent prognosticators in progression-free and
      disease-specific survival. CONCLUSIONS: Our results indicate that estimates of
      mean nuclear volume are prognostically superior to morphological grading of
      malignancy, such as Gleason score and WHO classification, in prostate cancer.

PMID- 7500474
TI  - The incidence of prostate cancer progression with undetectable serum prostate
      specific antigen in a series of 394 radical prostatectomies.
AB  - PURPOSE: Serum prostate specific antigen (PSA) has been reported to be a
      sensitive indicator of recurrent carcinoma after radical prostatectomy but it is
      not absolute. Disease progression with undetectable PSA levels has been described
      but the incidence of this phenomenon is unknown. MATERIALS AND METHODS: We
      retrospectively analyzed the records of 394 consecutive men who underwent radical
      prostatectomy between 1980 and 1991 to characterize the incidence of recurrent
      carcinoma despite undetectable serum PSA levels. RESULTS: Of the 394 men 133 had
      documented evidence of disease recurrence, 3 (2.3%) despite undetectable serum
      PSA levels (2 had local and systemic evidence of disease progression).
      Histological dedifferentiation characterized these recurrences. CONCLUSIONS:
      Although a post-prostatectomy detectable serum PSA level precedes clinical
      evidence of disease progression by years, rare patients (2.3% in our series) in
      whom recurrent disease is characterized by marked histological dedifferentiation
      will remain negative for PSA.

PMID- 7500475
TI  - What to expect from prostate cancer.

PMID- 7500476
TI  - Comparison of robotic versus human laparoscopic camera control .
AB  - PURPOSE: We investigated the accuracy and use of a robotic surgical arm compared
      to a human surgical assistant during urological laparoscopic surgery. MATERIALS
      AND METHODS: A total of 11 patients undergoing pelvic laparoscopic procedures
      that required identical bilateral surgical manipulations was evaluated. On 1 side
      a robotic surgical arm was used to manipulate the laparoscopic camera, while on
      the contralateral side the camera was positioned by a human surgical assistant.
      The side (left versus right) on which the robot was used was alternated with each
      case. Parameters assessed included operative time, erroneous camera motions,
      complications and outcome. RESULTS: All procedures were successfully completed
      without complications. Laparoscopic camera positioning was significantly steadier
      with less inadvertent movements when under robotic control (p < 0.0005).
      Operative times during dissections using the robot or human assistant were not
      statistically different. CONCLUSIONS: A robotic device can more effectively
      manipulate and accurately control the video endoscope than a human assistant
      during laparoscopic procedures.

PMID- 7500477
TI  - Analysis of maximum detrusor contraction power in relation to bladder emptying in
      patients with lower urinary tract symptoms and benign prostatic enlargement.
AB  - PURPOSE: We evaluate the relationship among post-voiding residual urine volume,
      bladder outlet obstruction and maximum detrusor contractility power. MATERIALS
      AND METHODS: We investigated urodynamically and retrospectively 242 elderly men
      with various grades of bladder outlet obstruction and symptoms. RESULTS: Residual
      urine predominantly correlated with bladder outlet obstruction and not with
      maximum detrusor contractility power. Maximum detrusor contractility power showed
      significant positive correlation with bladder outlet obstruction. Urodynamically,
      the detrusor compensates for bladder outlet obstruction with elevated maximum
      detrusor contractility power. Decay of contraction during micturition however,
      hampers effective emptying. CONCLUSIONS: Maximum detrusor contractility power
      limits for normal detrusor contractility must be related to bladder outlet
      obstruction grade. Based on the results of our analysis, new limits showing
      improved correlation with complete emptying were derived.

PMID- 7500478
TI  - Torsion of a spermatocele.

PMID- 7500479
TI  - Prostate Cancer Clinical Guidelines Panel Summary report on the management of
      clinically localized prostate cancer. The American Urological Association.
AB  - PURPOSE: The American Urological Association convened the Prostate Cancer
      Clinical Guidelines Panel to analyze the literature regarding available methods
      for treating locally confined prostate cancer, and to make practice policy
      recommendations based on the treatment outcomes data insofar as the data permit.
      MATERIALS AND METHODS: The panel searched the MEDLINE data base for all articles
      from 1966 to 1993 on stage T2 (B) prostate cancer and systematically analyzed
      outcomes data for radical prostatectomy, radiation therapy and surveillance as
      treatment alternatives. Outcomes considered most important were survival at 5, 10
      and 15 years, progression at 5, 10 and 15 years, and treatment complications.
      RESULTS: The panel found the outcomes data inadequate for valid comparisons of
      treatments. Differences were too great among treatment series with regard to such
      significant characteristics as age, tumor grade and pelvic lymph node status. The
      panel elected to display, in tabular form and graphically, the ranges in outcomes
      data reported for each treatment alternative. CONCLUSIONS: In making its
      recommendations, the panel presented treatment alternatives as options,
      identifying the advantages and disadvantages of each, and recommended as a
      standard that patients with newly diagnosed, clinically localized prostate cancer
      should be informed of all commonly accepted treatment options.

PMID- 7500480
TI  - Male epispadias.

PMID- 7500481
TI  - Correction of vesicoureteral reflux in children by endoscopic collagen injection:
      a prospective study.
AB  - PURPOSE: The aim of our prospective study was to evaluate the long-term results
      of correction of vesicoureteral reflux in children by subureteral submucosal
      endoscopic collagen injection. MATERIALS AND METHODS: Between May 1988 and June
      1994, 197 refluxing ureters in 148 children (grade III or IV, international
      grading system) were treated by collagen injection. Injection was done using
      general anesthesia and repeated 1 or 2 times if reflux persisted on the 1-month
      followup radionuclide cystogram. Cystography was repeated at 6 months, 2 years
      and 4 years. RESULTS: After 1 month, 6 months, 2 years and 4 years grades III and
      IV reflux were cured in 93.9%, 91.7%, 85.3% and 81.8%, respectively, of 132
      simple ureters. For the 27 duplex ureters success rates were 44.4%, 25.9%, 23.1%
      and 21.4%, respectively, after 1 month, 6 months, 2 years and 4 years. After
      failed injections neo-implantation was performed with no difficulty. CONCLUSIONS:
      Our results show that in simple ureters reflux, especially grade III, can be
      corrected by collagen injection. Results seem to be stable after 2 years of
      followup.

PMID- 7500482
TI  - Reinnervation of the rat bladder with a somatic nerve and a striated muscle flap.
AB  - PURPOSE: Current techniques of ventral sacral root stimulation to regain
      voluntary motor control of the decentralized urinary bladder depend upon intact
      parasympathetic innervation of the detrusor. We investigated techniques that
      might allow restoration of motor control of the bladder after efferent
      parasympathetic impairment. MATERIALS AND METHODS: In a chronic rat model, we
      evaluated whether motor control of a peripherally denervated bladder could be
      restored by transplantation of autologous excitable tissues and subsequent
      electrostimulation. Either a somatic nerve or a striated muscle flap was used as
      the transplant. RESULTS: Four months after the initial surgery,
      electrostimulation of the somatic nerve implant provoked bladder contractions--a
      response that was blocked by atropine. Stimulation of the nerve innervating the
      striated muscle flap also provoked bladder contractions; these were not affected
      by atropine and were slightly reduced by hexamethonium. CONCLUSION: Reinnervation
      of the bladder with somatic nerves or striated muscles is possible in principle.
      Future experiments will clarify the clinical significance of electrostimulation
      of such implants.

PMID- 7500483
TI  - A comparison between the effects of paraffin and plastic embedding of the normal
      and obstructed minipig detrusor muscle using the optical dissector.
AB  - PURPOSE: The purpose of this study was to estimate the relative shrinkage of the
      normal, obstructed and recovery minipig urinary bladder by comparing tissues from
      the same bladders embedded in paraffin or plastic. MATERIALS AND METHODS: Optical
      dissectors were used to make nucleus numerical density estimates in thick
      paraffin and plastic sections from the same bladder. The ratio of the 2 numerical
      densities depends only on differences in tissue shrinkage. In 9 minipigs a
      partial bladder outlet obstruction was created by implanting a 6 to 7 mm. Teflon
      ring around the proximal urethra. After an obstruction period (median 63 days)
      the ring was removed and after a recovery period (median 60 days) the animals
      were sacrificed. Biopsies were taken prior to obstruction, at removal of
      obstruction, and after recovery and were processed for paraffin and plastic
      sections to evaluate relative shrinkage. Two control pigs were sham-operated and
      biopsies taken at the same 3 time points. RESULTS: The optical dissector method
      was found to be an easy way to estimate the relative shrinkage of paraffin
      embedded bladder tissue in proportion to plastic-embedded tissue. Both in human
      and minipig bladders, paraffin embedding caused a relative shrinkage of about 30%
      in proportion to plastic embedding. Both the obstructed and recovery detrusor
      muscles responded to embedding by either method in a manner indistinguishable
      from the normal bladder. CONCLUSION: When dealing with stereological evaluation
      of the detrusor muscle, the relative shrinkage of the embedded normal, obstructed
      and recovery bladder tissue can be ignored.

PMID- 7500484
TI  - Effects of vamicamide on urinary bladder functions in conscious dog and rat
      models of urinary frequency.
AB  - PURPOSE: To investigate the usefulness of vamicamide, (+/-)-(2R*, 4R*)-4
      dimethylamino-2-phenyl-2-(2-pyridyl)valeramide, as a novel drug for the treatment
      of urinary frequency and incontinence. MATERIALS AND METHODS: Urinary frequency
      was evaluated in specially devised conscious dog and rat models by investigating
      the effects of the drug on urinary bladder function of these animals by
      cystometrography. RESULTS: In the dog model with transected hypogastric nerves,
      the bladder volume at micturition (bladder capacity) was less than 50% that of
      the sham-operated dog, and in the rat model with bilateral lesioning of nuclei
      basalis, a part of the brain, by ibotenic acid injection, bladder capacity was
      about 50% that of the sham-operated rat. Other bladder functions in both models
      were unchanged. In the dog model, orally administered vamicamide at 0.32 and 1.0
      mg./kg. significantly increased bladder capacity and did not change residual
      urine volume or micturition pressure. Oxybutynin 0.10 mg./kg., one of the most
      popular drugs for the treatment of urinary frequency and incontinence, or
      atropine 0.10 mg./kg. induced significant increases in bladder capacity similarly
      to vamicamide at 0.32 mg./kg. In the rat model, oral vamicamide 0.32 mg./kg. also
      significantly increased bladder capacity and did not change micturition pressure
      or threshold pressure. Again, oxybutynin 0.10 mg./kg. or atropine 0.32 mg./kg.
      had almost the same effects as vamicamide 0.32 mg./kg. CONCLUSIONS: These
      findings suggest that vamicamide should be useful for the treatment of urinary
      frequency.

PMID- 7500485
TI  - Local expression of cytokine messenger RNA in rat model of Escherichia coli
      epididymitis.
AB  - PURPOSE: In order to investigate whether cytokines play an important role in the
      regulation of host defense against bacterial epididymitis, we examined the local
      expression of cytokine mRNA in a rat model of Escherichia coli epididymitis.
      MATERIALS AND METHODS: Escherichia coli was inoculated into the spermatic cord of
      the rats and provoked epididymitis. At 6, 12, 24, 48, and 72 hours postinfection
      (p.i.) epididymides were harvested. We examined interleukin-6 (IL-6) and other
      inflammatory cytokine mRNAs in epididymides by Northern blotting and reverse
      transcriptase polymerase chain reaction (RT-PCR). Histopathological findings and
      immunohistochemistry for IL-6 were also examined. RESULTS: Infected epididymides
      expressed IL-6 mRNA maximally at 6 hours p.i. and then the signal decreased by
      Northern blotting. mRNA for IL-1 beta and TNF-alpha also increased within 6 hours
      by RT-PCR. Histopathological examination showed that no inflammatory cells were
      observed at 6 hours p.i. and that inflammatory changes were most prominent at 72
      hours p.i. Epididymal epithelium expressed IL-6 locally in response to local
      bacterial infection by immunohistochemistry. CONCLUSIONS: mRNA for IL-1 beta, IL
      6, and TNF-alpha is expressed locally in response to bacterial infection before
      inflammatory cell infiltration. This rapid expression in the epithelial cells may
      be important in host defense to local genital infection.

PMID- 7500486
TI  - Expression of markers for transitional cell carcinoma in normal bladder mucosa of
      patients with bladder cancer.
AB  - PURPOSE: Because we have found that random mucosal biopsies have no additional
      prognostic value to conventional histopathology, we studied biopsies of
      histologically normal bladder mucosa with several molecular markers believed to
      be associated with the development of transitional cell carcinoma. MATERIALS AND
      METHODS: Six groups of patients with an increasing stage of bladder tumor were
      selected: (1) benign disease (for example, benign prostatic hyperplasia, n = 8);
      (2-4) low (n = 10), intermediate (n = 9) and high risk (n = 7) superficial
      tumors; (5) progressive superficial tumors resistant to optimal conservative
      therapy (n = 6); (6) invasive or disseminated tumors at presentation (n = 5). We
      studied the expression of cytokeratin (used as an epithelial marker),
      fibronectin, E-cadherin (HECD-1), I-CAM, human leukocyte antigen (HLA)-I, HLA-II
      and epidermal growth factor receptor (EGF-R) in cold-cup biopsies of normal
      mucosa. RESULTS: Fibronectin, HECD-1, I-CAM and HLA-II expression showed no
      significant changes in the different groups. There was a significant increase in
      the expression of HLA-I (p = .003) and EGF-R (p = .0001) with a higher stage of
      the tumor. CONCLUSION: An increasing EGF-R expression in normal looking mucosa of
      patients with increasing stages of bladder tumors could be a prognostic factor or
      might indicate that this increase in expression is not tumor specific but is seen
      in the whole bladder.

PMID- 7500487
TI  - A monoclonal antibody identifies vimentin filaments in Sertoli cells and in a
      subset of epithelial cells in the rat epididymis, urinary bladder, and prostate.
AB  - PURPOSE: We describe a monoclonal antibody (Mab B2) against vimentin filaments in
      rat Sertoli cells and in a subset of epithelial cells in the rat epididymis,
      prostate and urinary bladder. MATERIALS AND METHODS: The immunoreactivity of Mab
      B2 was examined on cryostat sections and immunoblots and compared with the
      reactivity of a previously characterized monoclonal antibody against vimentin.
      RESULTS: While both antibodies recognized vimentin in Sertoli cells, only Mab B2
      recognized vimentin in urogenital tract epithelia. CONCLUSIONS: Vimentin is
      expressed in the urogenital tract, and differential reactivities of antibodies
      may be responsible for conflicting results reported elsewhere for vimentin
      expression.

PMID- 7500489
TI  - Medical educators confront the future.

PMID- 7500488
TI  - Effect of 15-deoxyspergualin (DSG) on rat kidney allograft: immunological
      mechanisms implicated in prolonged survival.
AB  - PURPOSE AND METHODS: The effect of short-term administration of 15
      deoxyspergualin (DSG), 5 mg./kg./day from postoperative days 4 to 7, on rat renal
      transplantation was studied. RESULTS: Although allografts treated with DSG
      survived longer than nontreated ones, cellular infiltration in both grafts did
      not differ. However, renal tubular cells of DSG-treated grafts proliferated well
      and escaped apoptotic cell death. A donor-specific tolerance 2 weeks after
      transplantation was developed, and cells with in vitro suppressor function were
      induced in such animals. CONCLUSIONS: Treatment with DSG appears to prevent
      lethal attack of effector cells on tubular cells in situ and to generate
      suppressor cells in the maintenance phase of graft enhancement.

PMID- 7500490
TI  - Military physicians of 12 nations cooperate in Haiti.

PMID- 7500491
TI  - International electronic link solves medical puzzle.

PMID- 7500492
TI  - From the Centers for Disease Control and Prevention. Air-bag-associated fatal
      injuries to infants and children riding in front passenger seats--United States.

PMID- 7500493
TI  - From the Centers for Disease Control and Prevention. Outbreak of gastrointestinal
      illness associated with consumption of seaweed--Hawaii, 1994.

PMID- 7500494
TI  - From the Centers for Disease Control and Prevention. Agricultural auger-related
      injuries and fatalities--Minnesota, 1992-1994.

PMID- 7500495
TI  - Anencephalic infants as organ donors.

PMID- 7500496
TI  - Anencephalic infants as organ donors.

PMID- 7500497
TI  - Anencephalic infants as organ donors.

PMID- 7500498
TI  - Anencephalic infants as organ donors.

PMID- 7500499
TI  - Access to health care and preventable hospitalizations.

PMID- 7500500
TI  - Access to health care and preventable hospitalization.

PMID- 7500501
TI  - Access to health care and preventable hospitalizations.

PMID- 7500502
TI  - The independent practice association.

PMID- 7500503
TI  - Brain death determination practices in children.

PMID- 7500504
TI  - X-rays and breast cancer.

PMID- 7500505
TI  - Characteristics of objects that cause choking in children.
AB  - OBJECTIVE: To characterize the types, shapes, and sizes of objects causing
      choking or asphyxiation in children and to compare these characteristics to
      current standards. DESIGN: To evaluate morbidity, retrospective 5-year medical
      record survey; to evaluate mortality, data reanalysis. SETTINGS: Pediatric
      hospital and consumer product testing laboratory. PATIENTS: All children (n =
      449) who underwent endoscopy for foreign body aspiration or ingestion at
      Children's Hospital of Pittsburgh (Pa) between 1989 and 1993 and children (n =
      449) whose deaths due to choking on man-made objects were recorded by the
      Consumer Product Safety Commission (CPSC) between 1972 and 1992. MAIN OUTCOME
      MEASURES: Objects removed from children's aerodigestive tracts were characterized
      by location, procedure for removal, and type. Objects causing death were
      characterized by type, shape, and consistency. Three-dimensional objects that had
      caused asphyxiation were analyzed by computer-simulated models. RESULTS: Of the
      165 children treated by endoscopy, 69% were 3 years of age or younger. Foreign
      bodies most often ingested or aspirated were food (in 36 children) and coins (in
      60 children). Of 449 children whose deaths after aspirating foreign bodies were
      reported to the CPSC, 65% were younger than 3 years. Balloons caused 29% of
      deaths overall. Conforming objects such as balloons caused a significantly (P <
      .001) higher proportion of deaths in those aged 3 years or older (60%) vs those
      younger than 3 years (33%). Of the 101 objects causing deaths that we could
      analyze, 14 met current standards for use by children of any age. CONCLUSIONS:
      Balloons pose a high risk of asphyxiation to children of any age. Changes in
      regulations regarding products intended for children's use might have prevented
      up to 14 (14%) of 101 deaths in this study.

PMID- 7500506
TI  - Physical and psychosocial functioning of women and men after coronary artery
      bypass surgery.
AB  - OBJECTIVE: To assess whether physical and psychosocial functioning differs
      between women and men after coronary artery bypass surgery. DESIGN: Observational
      cohort study. SETTING: Major teaching hospital. PATIENTS: A total of 454
      consecutive patients who received coronary artery bypass surgery from June 1989
      through March 1990. MAIN OUTCOME MEASURES: Nurse reviewers collected data on the
      severity of coronary artery disease and coexisting illnesses from medical
      records. A mailed survey measuring instrumental activities of daily living
      (IADLs), social activities, mental health, and vitality was completed by 306
      (70.2%) of 436 patients who were alive 6 months after surgery. Functioning on
      each scale was adjusted for age, marital status, education, severity of angina,
      recent myocardial infarction, congestive heart failure, and coexisting illnesses
      at the time of surgery. RESULTS: Before surgery, women were much more likely than
      men to have had class IV angina (50.9% vs 30.4%), a recent myocardial infarction
      (32.1% vs 18.0%), and congestive heart failure (34.0% vs 17.6%) (all P < .002).
      On a range from 0 (severe impairment) to 100 (no impairment), adjusted
      postoperative functioning was equivalent for women and men in IADLs (86.7 vs
      89.1), social activities (95.2 vs 95.3), mental health (72.6 vs 76.0), and
      vitality (58.1 vs 62.5) (all P > .20). Women reported similar or greater adjusted
      improvements than men for IADLs (27.2 vs 19.6, P = .08), social activities (20.8
      vs 8.0, P = .002), mental health (11.2 vs 5.7, P = .05), and vitality (22.2 vs
      12.9, P = .04). CONCLUSIONS: Women were more severely ill than men at the time of
      coronary artery bypass surgery, but women and men reported similar physical and
      psychosocial functioning 6 months after surgery. These findings demonstrate
      important functional benefits of this procedure among both women and men.

PMID- 7500507
TI  - Effects of lowering elevated LDL cholesterol on the cardiovascular risk of
      lipoprotein(a).
AB  - OBJECTIVE: To determine if lowering elevated low-density lipoprotein cholesterol
      (LDL-C) levels offsets the adverse effect of raised lipoprotein(a) (Lp[a]) levels
      on coronary artery disease (CAC) in men. DESIGN: Randomized, double-blind,
      placebo-controlled trial of lipid lowering for CAD. SETTING: Post hoc analysis of
      the Familial Atherosclerosis Treatment Study. PARTICIPANTS: A total of 146 men
      aged 62 years or younger with CAD and apolipoprotein B levels of at least 125
      mg/dL. INTERVENTION: Patients received a Step II Diet and lovastatin (40 mg
      daily) plus colestipol (30 g daily), niacin (4 g daily) plus colestipol, or
      placebo (plus colestipol if LDL-C > 90th percentile) for 2.5 years. They were
      grouped by their LDL-C responses: "minimal" if LDL-C decreased by 10% or less
      from baseline (mean [SD] change, +6% [13%]) and "substantial" if LDL-C decreased
      more than 10% (mean [SD] change, -40% [16%]). MAIN OUTCOME MEASURE: Impact of
      lowering elevated LDL-C on the cardiac event rate (death, myocardial infarction,
      and revascularization for refractory ischemia) and CAD change associated with
      elevated Lp(a). RESULTS: In multivariate analyses, the best correlate of baseline
      CAD severity was Lp(a) (r = 0.30; P < .001). For 36 patients with minimal LDL-C
      reduction, CAD progression correlated only with in-treatment Lp(a) levels (r =
      0.45; P < .01), but for 84 patients with substantial LDL-C reduction, disease
      regressed and its change correlated with in-treatment LDL-C (r = 0.24; P < .05)
      but not with Lp(a) (r = -0.05). Lipoprotein(a) levels were not significantly
      altered in either group. For 40 patients with Lp(a) at the 90th percentile or
      higher, events were frequent (39%) if reduction of LDL-C was minimal, but were
      few (9%) if reduction was substantial (relative risk, 0.23; 95% confidence
      interval, 0.06 to 0.99). CONCLUSIONS: In men with CAD and elevated LDL-C, Lp(a)
      levels were dominant correlates of baseline disease severity, its progression,
      and event rate over 2.5 years. However, with substantial LDL-C reductions,
      persistent elevations of Lp(a) were no longer atherogenic or clinically
      threatening. This provides a possible direction for treatment in such patients
      with elevated Lp(a) and LDL-C.

PMID- 7500508
TI  - Nursing home residents' preferences for life-sustaining treatments.
AB  - OBJECTIVES: To determine life-sustaining treatment preferences among nursing home
      residents, whether information regarding cardiopulmonary resuscitation (CPR)
      affected these preferences, and with whom treatment preferences had been
      discussed, and to identify factors associated with CPR preferences. DESIGN: In
      person survey. SETTING: Forty-nine randomly selected nursing homes. SUBJECTS:
      Four hundred twenty-one randomly selected nursing home residents capable of
      making decisions. MAIN OUTCOME MEASURES: Preferences regarding CPR,
      hospitalization, and enteral tube feedings, and individual factors associated
      with CPR preferences. RESULTS: Of 1458 randomly selected nursing home residents
      assessed for the ability to participate in the study, 552 residents (38%) were
      eligible to participate and 421 agreed to be interviewed. Sixty percent of
      participants able to participate in the decision reported that they would elect
      CPR, 89% would choose hospitalization if seriously ill, and 33% would elect
      enteral tube feedings if no longer able to eat because of permanent brain damage.
      Individual factors associated with preferences for CPR included the following:
      African-American ethnicity, high self-reported physical mobility, belief that
      most important medical care decisions should be made by the doctor, moderate-to
      severe impairment in daily decision-making skills, and not having a spouse.
      Fourteen percent changed their preference from preferring CPR to not preferring
      CPR after receiving additional information about CPR procedures. Twelve percent
      reported having discussed preferences with health care providers, and 31%
      discussed preferences with family members. CONCLUSIONS: More than half of nursing
      home residents capable of making decisions preferred the use of CPR. Few had
      discussed their preferences with health care providers. Individual preferences
      should be assessed when considering the use of life-sustaining treatments.

PMID- 7500509
TI  - Increased incidence of levodopa therapy following metoclopramide use.
AB  - OBJECTIVE: To determine whether there is an increase in use of antiparkinsonian
      therapy in older persons taking metoclopramide hydrochloride. DESIGN: Case
      control study. SETTING: New jersey Medicaid program. PATIENTS: Medicaid enrollees
      aged 65 years and older. Cases were patients newly prescribed a levodopa
      containing medication (n = 1253); a secondary case group were patients newly
      prescribed an anticholinergic antiparkinsonian drug (n = 2377). The control group
      consisted of 16435 Medicaid enrollees older than 65 years who were not users of
      any antiparkinsonian therapy. MAIN OUTCOME MEASURES: We used logistic regression
      to determine the odds ratio (OR) for the initiation of antiparkinsonian therapy
      in patients using metoclopramide relative to nonusers, after adjusting for age,
      sex, race, nursing home residence, exposure to antipsychotic medication, and days
      hospitalized. RESULTS: Metoclopramide users were three times more likely to begin
      use of a levodopa-containing medication compared with nonusers (OR = 3.09; 95%
      confidence interval [Cl], 2.25 to 4.26). Risk increased with increasing daily
      metoclopramide dose: the OR was 1.19 (95% Cl, 0.50 to 2.81) for more than 0 to 10
      mg per day, 3.33 (95% Cl, 1.98 to 5.58) for more than 10 to 20 mg per day, and
      5.25 (95% Cl, 1.16 to 8.50) for more than 20mg per day. The effect persisted
      after adjustment for demographic, health service utilization, and medication use
      variables. The OR for initiation of anticholinergic antiparkinsonian drugs was
      also elevated in metoclopramide users. CONCLUSION: Metoclopramide use confers an
      increased risk for the initiation of treatment generally reserved for the
      management of idiopathic Parkinson's disease in patients with drug-induced
      parkinsonian symptoms, which should be ruled out before starting dopaminergic
      therapy for this condition.

PMID- 7500510
TI  - Ethical aspects of banking placental blood for transplantation.
AB  - Transplantation of blood cells harvested from the umbilical cord immediately
      after birth has been effective in repopulating the bone marrow. These placental
      blood transplantations may be safer than conventional bone marrow
      transplantations and may suspend the need to harvest bone marrow, a process
      fraught with difficulties. Further understanding and advancement of this emerging
      technology require developing large banks of placental blood. In this article, we
      examine some of the ethical issues associated with placental blood banking,
      including (1) questions about ownership of the tissue, (2) the necessity and
      nature of obtaining informed consent from parents for harvesting placental blood
      and the information-gathering process associated with it, (3) obligations to
      notify parents and children of the results of medical testing for infectious
      diseases and genetic information, (4) matters of privacy and confidentiality
      related to such information, and (5) the need for fair and equitable harvesting
      of and access to placental blood.

PMID- 7500511
TI  - Informed consent for genetic research on stored tissue samples.
AB  - OBJECTIVE: To develop recommendations for obtaining adequate informed consent in
      the future when gathering tissue samples that may be used for genetic studies and
      defining the circumstances under which it is necessary to obtain further consent
      if tissue samples already in hand are to be used for such research. PARTICIPANTS:
      Scientists, ethicists, lawyers, and consumers selected by the National Center for
      Human Genome Research and the Centers for Disease Control and Prevention to
      represent a wide array of opinions. EVIDENCE: Statutes, regulations, and cases
      and articles on law and ethics. CONSENSUS PROCESS: Initial workshop, followed by
      circulation of several drafts of this document with opportunities for comment by
      workshop participants and others as well as smaller meetings involving
      participants with widely differing views. CONCLUSION: Genetic research using
      stored tissue samples poses an array of benefits and risks to individuals,
      researchers, and society. As a result, the workshop participants conclude that
      (1) informed consent is required for all genetic research using linkable samples
      unless conditions for limitation or waiver are met; (2) informed consent is not
      required for genetic research using anonymous samples but may be considered if
      identifiers are to be removed from currently linkable samples; (3) institutional
      review boards could usefully review all protocols that propose to use samples for
      genetic research; and (4) further work regarding these issues is warranted.

PMID- 7500512
TI  - Childhood immunization registries. A national review of public health information
      systems and the protection of privacy.

PMID- 7500513
TI  - Users' guides to the medical literature. IX. A method for grading health care
      recommendations. Evidence-Based Medicine Working Group.

PMID- 7500514
TI  - Designing the death out of balloons.

PMID- 7500516
TI  - Reengineered monoclonal antibodies step up to the plate in cancer studies.

PMID- 7500515
TI  - Research and stored tissues. Persons as sources, samples as persons?

PMID- 7500517
TI  - Miami medical school leads the way in assisting Haitians while training family
      medicine residents.

PMID- 7500518
TI  - From the Health Care Financing Administration.

PMID- 7500519
TI  - From the Centers for Disease Control and Prevention. First 500,000 AIDS cases-
      United States, 1995.

PMID- 7500520
TI  - From the Centers for Disease Control and Prevention. Deaths associated with a
      purported aphrodisiac--New York City, February 1993-May 1995.

PMID- 7500521
TI  - Interaction of epinephrine and beta-blockers.

PMID- 7500522
TI  - Alcohol availability and alcoholism.

PMID- 7500523
TI  - Projections for the generalist physician workforce.

PMID- 7500524
TI  - Projections for the generalist physician workforce.

PMID- 7500525
TI  - Cigarette smoking and vertebral body deformity.

PMID- 7500526
TI  - Restricted randomization in randomized controlled trials.

PMID- 7500527
TI  - Percentage of CD4 lymphocytes and risk of AIDS.

PMID- 7500528
TI  - Are reminder systems a form of CME?

PMID- 7500529
TI  - Marijuana as medicine.

PMID- 7500530
TI  - Marijuana as medicine.

PMID- 7500531
TI  - Marijuana as medicine.

PMID- 7500532
TI  - Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients
      with nonvalvular atrial fibrillation.
AB  - OBJECTIVE: To examine the cost-effectiveness of prescribing warfarin sodium in
      patients who have nonvalvular atrial fibrillation (NVAF) with or without
      additional stroke risk factors (a prior stroke or transient ischemic attack,
      diabetes, hypertension, or heart disease). DESIGN: Decision and cost
      effectiveness analyses. The probabilities for stroke, hemorrhage, and death were
      obtained from published randomized controlled trials. The quality-of-life
      estimates were obtained by interviewing 74 patients with atrial fibrillation.
      Costs were estimated from literature review, phone survey, and Medicare
      reimbursement. PATIENTS: In the base case, the patients were 65 years of age and
      good candidates for warfarin therapy. INTERVENTIONS: Treatment with warfarin,
      aspirin, or no therapy in the decision analytic model. MAIN OUTCOME MEASURES:
      Quality-adjusted survival and marginal cost-effectiveness of warfarin as compared
      with aspirin or no therapy. RESULTS: For patients with NVAF and additional risk
      factors for stroke, warfarin therapy led to a greater quality-adjusted survival
      and to cost savings. For patients with NVAF and one additional risk factor,
      warfarin therapy cost $8000 per quality-adjusted life-year saved. For 65-year-old
      patients with NVAF alone, warfarin cost about $370,000 per quality-adjusted life
      year saved, as compared with aspirin therapy. However, for 75-year-old patients
      with NVAF alone, prescribing warfarin cost $110,000 per quality-adjusted life
      year saved. For patients who were not prescribed warfarin, aspirin was preferred
      to no therapy on the basis of both quality-adjusted survival and cost in all
      patients, regardless of the number of risk factors present. CONCLUSIONS:
      Treatment with warfarin is cost-effective in patients with NVAF and one or more
      additional risk factors for stroke. In 65-year-old patients with NVAF but no
      other risk factors for stroke, prescribing warfarin instead of aspirin would
      affect quality-adjusted survival minimally but increase costs significantly.

PMID- 7500533
TI  - The association between midlife blood pressure levels and late-life cognitive
      function. The Honolulu-Asia Aging Study.
AB  - OBJECTIVE: To assess the long-term relationship of midlife blood pressure levels
      to late-life cognitive function. DESIGN: The 4678 surviving cohort members of the
      prospective Honolulu Heart Program (baseline, 1965-1968) were examined a fourth
      time in 1991 through 1993 and given a cognitive test. PARTICIPANTS: The subjects
      were 3735 Japanese-American men living in Hawaii in the community or in
      institutions, with an average age of 78 years at the fourth examination. MAIN
      OUTCOME MEASURES: Cognitive function, measured by the 100-point Cognitive
      Abilities Screening Instrument (CASI), was categorized into good (reference: a
      CASI score of 92 to 100), intermediate (< 92 to 82), and poor (< 82). Midlife
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were
      measured in 1965, 1968, and 1971. A respondent was classified into the following
      categories if two of three measurements fell into the following groups: for SBP,
      < 110, 110 to 139, 140 to 159, and > or = 160 mm Hg; and for DBP, < 80, 80 to 89,
      90 to 94, and > or = 95 mm Hg. RESULTS: When we controlled for age and education,
      the risk for intermediate and poor cognitive function increased progressively
      with increasing level of midlife SBP category (P for trend < .03 and < .001,
      respectively). For every 10-mm Hg increase in SBP there was an increase in risk
      for intermediate cognitive function of 7% (95% confidence interval [CI], 3% to
      11%) and for poor cognitive function of 9% (95% CI, 3% to 16%). Adjustment for
      prevalent stroke, coronary heart disease, and subclinical atherosclerosis reduced
      the strength of the relationship between midlife SBP and poor cognitive function
      to 5% (95% CI, 0% to 12%). The level of cognitive function was not associated
      with midlife DBP. CONCLUSIONS: Midlife SBP is a significant predictor of reduced
      cognitive function in later life. Early control of SBP levels may reduce the risk
      for cognitive impairment in old age.

PMID- 7500534
TI  - Hospital and 1-year survival of patients admitted to intensive care units with
      acute exacerbation of chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To describe outcomes and identify variables associated with hospital
      and 1-year survival for patients admitted to an intensive care unit (ICU) with an
      acute exacerbation of chronic obstructive pulmonary disease (COPD). DESIGN:
      Prospective, multicenter, inception cohort study. SETTING: Forty-two ICUs at 40
      US hospitals. PATIENTS: A total of 362 admissions for COPD exacerbation selected
      from the Acute Physiology and Chronic Health Evaluation (APACHE) III database of
      17,440 ICU admissions. MEASUREMENTS AND RESULTS: Hospital mortality for the 362
      admissions was 24%. For the 167 patients aged 65 years or older, mortality was
      30% at hospital discharge, 41% at 90 days, 47% at 180 days, and 59% at 1 year.
      Median survival for all patients was 224 days, and median survival for the
      patients who died within 1 year was 30.5 days. On multiple regression analysis,
      variables associated with hospital mortality included age, severity of
      respiratory and nonrespiratory organ system dysfunction, and hospital length of
      stay before ICU admission. Development of nonrespiratory organ system dysfunction
      was the major predictor of hospital mortality (60% of total explanatory power)
      and 180-day outcomes (54% of explanatory power). Respiratory physiological
      variables (respiratory rate, serum pH, PaCO2, PaO2, and alveolar-arterial
      difference in partial pressure of oxygen [PAO2-PaO2]) indicative of advanced
      dysfunction were more strongly associated with 180-day mortality rates (22% of
      explanatory power) than hospital death rates (4% of explanatory power). After
      controlling for severity of illness, mechanical ventilation at ICU admission was
      not associated with either hospital mortality or subsequent survival.
      CONCLUSIONS: Patients with COPD admitted to an ICU for an acute exacerbation have
      a substantial hospital mortality (24%). For patients aged 65 years or older,
      mortality doubles in 1 year from 30% to 59%. Hospital and longer-term mortality
      is closely associated with development of nonrespiratory organ system
      dysfunction; severity of the underlying respiratory function substantially
      influences mortality following hospital discharge. The need for mechanical
      ventilation at ICU admission did not influence either short- or long-term
      outcomes. Physicians should be aware of these relationships when making treatment
      decisions or evaluating new therapies.

PMID- 7500535
TI  - Ethnic differences in the use of peritoneal dialysis as initial treatment for end
      stage renal disease.
AB  - OBJECTIVE: To evaluate the influence of ethnicity on the use of peritoneal
      dialysis (PD) as initial treatment for end-stage renal disease (ESRD) after
      controlling for other patient characteristics. DESIGN: Inception cohort analysis
      of incident ESRD patients. PATIENTS: All African-American and white patients (N =
      10,726) who began treatment for ESRD at dialysis centers in North Carolina, South
      Carolina, and Georgia and reported to ESRD Network 6 between January 1, 1989, and
      December 31, 1991. MAIN OUTCOME MEASURE: Odds ratios (ORs) of the association
      between ethnicity and PD as initial treatment modality. RESULTS: African-American
      patients were 56% less likely than whites to use PD (OR, 0.44; 95% confidence
      interval [CI], 0.40 to 0.49). This difference persisted (OR, 0.45; 95% CI, 0.38
      to 0.52) after multivariable adjustment for age, education, social support, home
      ownership, functional status, albumin level, hypertension, history of myocardial
      infarction, peripheral neuropathy, and comorbid diabetes. CONCLUSIONS: Ethnic
      differences in initial PD use cannot be explained by many demographic,
      socioeconomic, and comorbid factors associated with the use of PD as initial
      treatment for ESRD.

PMID- 7500536
TI  - Comparison of throat culture methods for the recovery of group A streptococci in
      a pediatric office setting.
AB  - OBJECTIVE: To compare a single-plate method for the recovery of group A
      streptococci with other methods that have recently been reported as being
      significantly more sensitive. DESIGN: Throat swabs were allowed to dry for 2 to 6
      hours before inoculating 5% sheep blood agar plates. Stabs were made into the
      agar, bacitracin disks were placed on the primary plates, and the cultures were
      incubated aerobically. Using duplicate throat swabs, the recovery rates of the
      above method were compared with the following ones: a carbon dioxide-enhanced
      incubation atmosphere, an anaerobic atmosphere with a selective blood agar
      medium, and a Todd-Hewitt broth medium. SETTING: A five-pediatrician office.
      PATIENTS: A total of 301 pediatric patients with pharyngitis were evaluated using
      all comparative methods. In addition, duplicate swabs from 590 pediatric patients
      were compared with each other using the same single-plate method. RESULTS: There
      were no significant differences between any of the methods. The sensitivity of
      the single-plate method compared with selective plates incubated anaerobically
      was 96%. CONCLUSIONS: In a pediatric office setting, a single-plate method using
      aerobic incubation was adequately sensitive for the recovery of group A beta
      hemolytic streptococci. Transport medium, selective medium, carbon dioxide
      enhancement, and anaerobic incubation did not significantly improve recovery. The
      present federal regulations that restrict the use of nonselective media and
      bacitracin disks on primary plates should be reevaluated.

PMID- 7500537
TI  - Protecting children with chronic illness in a competitive marketplace.
AB  - Health care for children with chronic illnesses is significantly more expensive
      than for the average child. Children with chronic illnesses are especially
      vulnerable in a competitive health care environment because of the higher ongoing
      cost associated with treating their illnesses and the inherent pressures to
      reduce services to manage within the capitated rate. To minimize the adverse
      impact a competitive market could have on these children, a "carve-out" for
      specific medical conditions is discussed. A capitation pricing system that
      reflects their higher costs is proposed, as well as a delivery system that is
      focused on their needs.

PMID- 7500538
TI  - The WHO analgesic ladder for cancer pain management. Stepping up the quality of
      its evaluation.
AB  - OBJECTIVE: To perform a systematic review of studies evaluating the effectiveness
      of the World Health Organization (WHO) analgesic ladder as an intervention for
      cancer pain management. DATA SOURCES: Systematic search of MEDLINE from 1982 to
      1995, hand search of textbooks and meeting proceedings, reference lists, and
      direct contact with authors. STUDY SELECTION: Studies of any methodological
      design were included if they evaluated patients with cancer pain treated
      according to the WHO analgesic ladder and if the studies provided enough
      information to estimate the proportion of patients who achieved adequate
      analgesia with the use of the ladder. The strength of the evidence provided by
      each study was assessed separately by both authors using current concepts. DATA
      EXTRACTION: From the hard copy of each study report, the first author's name,
      publication year, study design, number of dropouts per study, and proportion of
      patients with adequate analgesia in each study were extracted. DATA SYNTHESIS:
      Eight studies purporting to evaluate the effectiveness of the WHO ladder were
      included in the review. Meta-analysis was not performed because the studies were
      case series with no control groups. The studies had other limitation: none
      provided information on the conditions in which pain was assessed; two were
      retrospective; one had short follow-up periods; three had high withdrawal rates;
      and one had variable follow-up periods. Analgesia was adequate in 69% to 100% of
      patients analyzed in the studies. CONCLUSIONS: The studies available provide
      valuable information on the course of cancer pain and its treatment. However, the
      evidence they provide is insufficient to estimate confidently the effectiveness
      of the WHO analgesic ladder for the management of cancer pain. Until results from
      carefully designed controlled trials are available, it would be inappropriate to
      judge the performance of clinicians, programs, and institutions or to design
      policies based on such evidence.

PMID- 7500539
TI  - Quality improvement guidelines for the treatment of acute pain and cancer pain.
      American Pain Society Quality of Care Committee.
AB  - OBJECTIVE: To develop quality improvement (QI) guidelines and programs to improve
      treatment outcomes for patients with acute pain and cancer pain. PARTICIPANTS:
      Twenty-four members of the American Pain Society (APS) participated in preparing
      the statement, including 15 nurses (oncology, general medical-surgical nursing,
      pediatrics, and QI research), seven physicians (clinical pharmacology, neurology,
      anesthesiology, radiation oncology, and physiatry), one psychologist, and one
      statistician. Participants were self-selected from the 3000 members of the APS,
      which supported the process and held annual open committee meetings and
      scientific symposia beginning in 1988. EVIDENCE: MEDLINE was searched (1980 to
      1995) to identify all articles on pain assessment, treatment of acute pain or
      cancer pain, and QI or education related to pain. CONSENSUS PROCESS: Following
      panel discussions, one member (M.B.M.) prepared successive drafts and circulated
      them to the panel and APS membership for comments. After publication of a
      prototype version in 1991, 14 panelists carried out formal studies of
      implementation of the guidelines at three medical centers. This article was
      prepared based on this research, a new literature review, and suggestions from 50
      pain clinicians and researchers. CONCLUSIONS: Quality improvement programs to
      improve treatment of acute pain and cancer pain should include five key elements:
      (1) Assuring that a report of unrelieved pain raises a "red flag" that attracts
      clinicians' attention; (2) making information about analgesics convenient where
      orders are written; (3) promising patients responsive analgesic care and urging
      them to communicate pain; (4) implementing policies and safeguards for the use of
      modern analgesic technologies; and (5) coordinating and assessing implementation
      of these measures. Several short-term studies suggest that this QI approach may
      improve patient satisfaction and facilitate recognition of institutional
      obstacles to optimal pain treatment, but it is not a panacea for undertreated
      pain. By making the magnitude of the problem apparent and committing the
      institution to change, pain treatment QI programs can provide a foundation for a
      multifaceted approach that includes education of clinicians and patients, design
      of informational tools to minimize errors in prescribing, and improved
      coordination of the process of assessing and treating pain.

PMID- 7500540
TI  - When will adequate pain treatment be the norm?

PMID- 7500541
TI  - Human rights violations among Bhutanese refugees.

PMID- 7500542
TI  - Familial aggregation of dilated cardiomyopathy--evaluation of clinical
      characteristics and prognosis.
AB  - To investigate the prevalence, clinical characteristics, and prognosis of
      familial cases of idiopathic dilated cardiomyopathy (IDC), family screenings were
      carried out in 117 IDC patients and their relatives. Familial occurrence was
      suspected in 29 families (25%). Ten families (9%) with 24 patients were confirmed
      to be familial, but the other 19 families (16%) remained suspected. The age at
      the time of diagnosis was lower and the cardiac symptoms tended to be milder in
      the familial group than in the non-familial group, but there were no differences
      in other clinical parameters. There was also no difference in the survival rate.
      However, when only NYHA class III and IV patients were selected, the 1-year and 5
      year survival rates were lower in the familial group than in the non-familial
      group. Congestive heart failure was the most common cause of death in the non
      familial group, while sudden death was the most common cause of death in the
      familial group. Among familial IDC patients who were deceased, the left
      ventricular end-diastolic pressure was higher and the cardiac index was lower at
      the time of diagnosis than those in patients who were still alive. We conclude
      that, since the prognosis of familial IDC patients is poor once their cardiac
      symptoms become severe, early diagnosis and treatment are extremely important.

PMID- 7500543
TI  - Clinical usefulness of 123I-metaiodobenzylguanidine myocardial scintigraphy in
      diabetic patients with cardiac sympathetic nerve dysfunction.
AB  - To assess the clinical utility of 123I-metaiodobenzylguanidine (MIBG)
      scintigraphy in evaluating cardiac sympathetic nerve disturbance in diabetic
      patients, we performed MIBG scintigraphy in 18 diabetic patients and 11 normal
      controls. Diabetic patients with symptomatic neuropathy (DM2) had a significantly
      lower heart to mediastinum uptake ratio than did those without neuropathy or
      normal controls in initial and delayed images (initial image, 1.90 +/- 0.27 vs
      2.32 +/- 0.38, 2.41 +/- 0.40, p< 0.01; delayed image, 1.80 +/- 0.31 vs 2.48 +/-
      0.35 2.56 +/- 0.28, p < 001, respectively). Defect score, assessed visually, were
      higher in DM2 patients than in patients in the other two groups (initial image, 7
      +/- 2.6 vs 1.5 +/- 1.9, 0.7 +/- 0.9; delayed image 10.6 +/- 3.3 vs 4.0 +/- 2.5,
      1.7 +/- 1.6 p < 0.01, respectively). The maximum washout rate in DM2 patients was
      also higher than those in patients in the other two groups. The findings of these
      indices obtained from MIBG scintigraphy coincided with the % low-frequency power
      extracted from heart rate fluctuations using a power spectral analysis and the
      results of the Schellong test, which were used to evaluate sympathetic function.
      These results suggest that MIBG scintigraphy may be useful for evaluating cardiac
      sympathetic nerve disturbance in patients with diabetes.

PMID- 7500544
TI  - Improvement of coronary vasomotion with eicosapentaenoic acid does not inhibit
      acetylcholine-induced coronary vasospasm in patients with variant angina.
AB  - Impaired function of the endothelium may be a mechanism of the coronary vasospasm
      induced by acetylcholine. We examined whether purified eicosapentaenoic acid
      (EPA), a major component of fish oil, improves the coronary vasomotion in
      response to acetylcholine, and the effect of purified EPA on acetylcholine (ACh)
      induced coronary vasospasm in 22 patients with variant angina. ACh was infused
      into the coronary artery both before and after 4 months of EPA treatment (EPA 1.8
      g/day, n = 12). In the control group (n = 10) that did not receive EPA, the
      response of the coronary diameter to ACh did not change over time. In the EPA
      treated group, the cholinergic response in non-spastic sites changed from
      vasoconstriction to vasodilation, while ACh-induced coronary vasospasm persisted
      at the spastic sites. Therefore, EPA treatment improved the coronary vasomotor
      responsiveness to ACh, but did not inhibit ACh-induced coronary vasospasm.

PMID- 7500545
TI  - Changes in the E/A ratio induced by handgrip-exercise are related to changes in
      the plasma atrial natriuretic peptide level, but not to changes in brain
      natriuretic peptide in mild essential hypertension.
AB  - We investigated the relationship between changes in atrial natriuretic peptide
      (ANP) and brain natriuretic peptide (BNP) and changes in cardiac function during
      mild exercise in patients with mild hypertension. The handgrip test (HGT) was
      performed by 21 untreated, mildly hypertensive patients, mean age 45 +/- 5 years.
      M-mode and pulse Doppler echocardiograms were recorded before and during HGT. In
      7 patients (Group A), diastolic function, which was determined by the peak early
      velocity and peak atrial velocity (E/A) ratio using Doppler echocardiography was
      attenuated during HGT (1.19 +/- 0.21 TO 1.04 +/- 0.16, p < 0.05). There was no
      change in diastolic function in the remaining 14 patients, left atrial diameter,
      cardiac index, ejection fraction, plasma renin activity, plasma norepinephrine,
      blood pressure, nor heart rate were different between the two groups. While ANP
      was increased in Group A during HGT (from 41.0 +/- 18.2 to 54.0 +/- 24.1 pg/ml, p
      < 0.05) it was unchanged in Group B (36.8 +/- 16.3 to 33.5 +/- 11.9 pg/ml). BNP
      did not change in either Group (Group A: 2.9 +/- 3.1 to 3.0 +/- 3.4 pg/ml, Group
      B: 2.6 +/- 1.6 to 3.6 +/- 4.8 pg/ml). The percent change in ANP during HGT did
      not correlate with the percent change in BNP. Thus, the impairment of cardiac
      functional reserve appeared to influence ANP excretion in patients with mild
      hypertension.

PMID- 7500546
TI  - Comparable effects of angiotensin II and converting enzyme blockade on
      hemodynamics and cardiac hypertrophy in spontaneously hypertensive rats.
AB  - Angiotensin-converting enzyme inhibitors may regress left ventricular hypertrophy
      (LVH) without decreasing blood pressure (BP). The aim of the present study was to
      compare the effects of low and high doses of lisinopril and the angiotensin II
      receptor antagonist TCV116 (TCV) on LVH and hemodynamics in spontaneously
      hypertensive rats (SHR). Lisinopril (0.5 and 3 mg/kg per day) and TCV (0.3 mg/kg
      per day) were given to 8-week-old male SHR daily for 2 weeks. Untreated SHR and
      Wistar-Kyoto rats (WKY) served as controls. Untreated SHR had a greater left
      ventricular (LV) weight than WKY (p < 0.01). Lisinopril (3 mg/kg per day)
      decreased both LV weight and BP. Lisinopril (0.5 mg/kg per day) significantly
      decreased LV weight, but not BP. In contrast, although TCV significantly
      decreased BP, LVH was not suppressed. Renal blood flow (RBF) in untreated SHR was
      less than that in WKY (p < 0.05), but was increased with either lisinopril (3
      mg/kg per day)-treated rats (p< 0.05). These findings suggest that factors other
      than afterload reduction play a role in the regression of LVH with lisinopril,
      whereas a longer duration of treatment and/or a higher dose may be necessary with
      TCV. Despite the decrease in BP, TCV normalized RBF in SHR, perhaps due to the
      blockade of renal angiotensin II.

PMID- 7500547
TI  - Changes in extracellular matrix components in cardiomyopathic Syrian hamster, BIO
      14.6.
AB  - We examined changes in the distribution of extracellular matrix components in the
      myocardium of cardiomyopathic Syrian hamsters (BIO 14.6). Fibronectin, laminin,
      and type IV collagen, and type I and III collagens were immunohistochemically
      stained by the avidin-biotin-peroxidase complex method, using a polyclonal
      antibody for each component. Hearts obtained from 4 stages of BIO 14.6
      cardiomyopathy were examined. Peri- and endomysial fibrosis increased as the
      disease progressed. Replacement and meshwork (perimysial fibrosis penetrating the
      intercellular space) fibrotic lesions appeared beginning in the 2nd stage, ie,
      the fibrotic and healing stage. All of the components examined, ie, fibronectin,
      laminin and type IV collagen, and type I and III collagens, were present in
      various fibrotic lesions and played a significant role in fibrotic changes
      throughout all of the stages of the disease. No primary deficit of any of these
      components was seen. An increased distribution of fibronectin was observed in
      both the enlarged peri-and endomysial spaces beginning in the initial stage, ie,
      the necrotic stage, when myocyte hypertrophy was inconspicuous, and distribution
      throughout the myocardium increased further as the disease progressed. Laminin
      and type IV collagen in the fibrotic lesions were not restricted to the myocyte
      membrane. Type III collagen was distributed in replacement and meshwork fibrotic
      lesions, and the extent of its distribution increased in proportion to that of
      type I collagen. The continuous increases in the distribution of fibronectin,
      laminin and type III collagen indicate that fibrotic changes occurred
      continuously in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500548
TI  - Fatal cerebral infarction in an asymptomatic young patient with primary
      antiphospholipid syndrome.
AB  - An 18-year-old woman with primary antiphospholipid syndrome developed a major
      cerebral infarction leading to brain death despite intensive treatment with
      steroids, urokinase, glyceol and heparin. Fatal strokes associated with this
      syndrome are rare. A computed tomographic scan of the brain suggested occlusion
      of the main trunk of the right middle cerebral artery. The titer of antibodies
      against cardiolipin/ beta 2-glycoprotein I complex in serum was extremely high.

PMID- 7500549
TI  - [Red blood cell parameters of healthy centenarians].
AB  - Since the number of centenarians is increasing rapidly in recent years, the
      establishment of normal ranges in red blood cell (RBC) parameters for healthy
      centenarians is necessary for diagnostic criteria of anemia. The subjects were
      129 centenarians consisting of 27 men (17; healthy, 69; low ADL) and 102 women
      (33; healthy, 69; low ADL) after excluding centenarians with diseases affecting
      RBC parameters. The t test was used for statistical evaluation. The mean RBC
      count for healthy centenarian men was 403 +/- 54.7 x 10(4)/microliters;
      hemoglobin (Hb) level, 12.4 +/- 1.3 g/dl; hematocrit (Hct), 38.2 +/- 3.9%; MVC,
      95.3 +/- 5.3 fl; MCH, 31.4 +/- 2.2 pg; and MCHC, 32.1 +/- 1.1%. Comparable
      results for healthy centenarian women were as follows: 375 +/- 43.9 x
      10(4)/microliters, 11.6 +/- 1.2 g/dl, 36.3 +/- 3.6%, 97.1 +/- 5.3 fl, 31.0 +/-
      2.3 pg, and 32.0 +/- 1.3%, respectively. The mean Hb for healthy centenarian
      women was significantly lower than that for healthy centenarian men. The mean
      RBC, Hb and hematocrit values for low ADL-centenarian men were lower than the
      comparable values for healthy centenarian men. Conversely, the mean MCV value for
      low ADL-centenarian men was higher than that for healthy centenarian men. There
      was no difference in any RBC parameter between healthy centenarian women and low
      ADL-centenarian women. In addition, there was no difference in any RBC parameter
      between centenarian women living in their own homes and those living in old-aged
      homes. This study demonstrated the normal ranges of RBC parameters for healthy
      centenarians, and lower RBC, Hb, and Hct values for low ADL-centenarian men.

PMID- 7500550
TI  - [A study of the efficacy of thrombolytic therapy for acute myocardial infarction
      in elderly patients].
AB  - We compared the short and long term outcome between an elderly group (E; aged 70
      year more, 17 cases) and a younger group (Y; less than 70 years, 95 cases).
      Reperfusion rates were similar in both groups (E; 70.6% vs Y; 67.3%). Reocclusion
      rates at predischarge CAG were similar in both groups (E; 70.6% vs Y; 67.3%).
      Reocclusion rates at predischarge CAG were similar in both groups (E; 7.2% vs Y;
      6.8%). Hospital cardiac deaths in E were higher than Y (E; 5.9% vs Y; 4.2%).
      Intestinal bleeding in E was more frequent than in Y (E; 5.9% vs Y; 3.2%). We
      concluded that thrombolytic therapy for acute myocardial infarction in elderly
      patients was useful, however bleeding complication in elderly patients were
      higher than in younger patients.

PMID- 7500551
TI  - [Geographical epidemiologic studies on factors associated with centenarians in
      Japan].
AB  - To explore factors associated with longevity, we studied geographic distribution
      of centenarians in Japan, based on 1990 the population census. We calculated the
      proportion of centenarians from ratio of number of centenarian to that of
      population aged 65 years or older. Centenarians in Japan consisted of number
      4,152 persons. By prefecture, Tokyo had the most centenarians (383), followed by
      Okinawa (193) and Fukuoka (151) prefectures. Fukui had the least (24), followed
      by Akita (26) and Ishikawa (29) prefectures. The proportion of centenarians in
      Japan was 21.6 (per 100,000 populations) in 1990. By prefecture, the highest
      proportion lived in Okinawa (133.8), whereas the fewest were found in Akita
      (8.9). The relationship between geographic distribution of centenarians and
      environmental factors and nutritional factors were analyzed. Correlation
      coefficients between proportion of centenarians and mean temperature, high
      quality of welfare work and of medical services, and having much leisure time
      were positively significant. As for nutritional factor, correlation coefficients
      between proportion of centenarians and protein (% of energy) was positively
      significant, while intake of total energy was negatively significant.

PMID- 7500552
TI  - [Restenosis after percutaneous transluminal coronary angioplasty in the elderly-
      risk factor analysis].
AB  - Utilization of percutaneous transluminal coronary angioplasty (PTCA) has
      dramatically expanded even in the management of elderly patients with coronary
      artery disease. However, restenosis after successful PTCA remains the major
      problem limiting the long-term efficacy of the procedure. Reported restenosis
      rates vary from 25 to 43%. In order to determine the relationship of restenosis
      to coronary risk factors in the elderly, we analyzed the data in 87 patients who
      had undergone PTCA and angiography before and 3 to 6 months after PTCA. Of these,
      29 patients were 65 years of age or older (elderly group) and 58 were less than
      65 years of age (younger group). Restenosis, defined as a luminal narrowing of
      greater than 50% at follow-up time, was found in 20 of the elderly group (69.0%),
      and in 26 (44.8%) of younger group (p < 0.0001). Total cholesterol, LDL
      cholesterol, apolipoprotein B (apo B), and the ratio of apoB/apoA1 in the elderly
      group were significantly lower than those in the younger group. HDL cholesterol
      levels were lower than 40 mg/dl in both groups (not significant). Each group was
      subdivided into two types; restenosis type and non-restenosis type. There were no
      significant differences in serum lipid, apolipoprotein, and lipoprotein(a) levels
      between the 2 subtypes in each group. The degree of coronary atherosclerosis
      calculated by Gensini's method, the number of damaged coronary vessels, diabetes
      mellitus, hypertension, and smoking did not appear to affect the rate of
      restenosis in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500553
TI  - [Ischemic cerebrovascular disease in patients with atrial fibrillation].
AB  - The purpose of this retrospective study was to elucidate 1) which subgroups are
      prone to have ischemic cerebrovascular disease (CVD) among patients with atrial
      fibrillation (Af), 2) vulnerable period of CVD after the diagnosis of chronic Af
      and 3) the clinical efficacy of antiplatelet therapy in chronic nonvalvular Af
      patients. During 9 years, a total of 479 patients included 124 cases with
      paroxysmal Af, 30 cases with paroxysmal Af initially which later changed to
      chronic Af and 325 cases with chronic Af were enrolled. Among these 355 cases
      with chronic Af, 57 cases had valvular heart disease (VHD). The results were as
      follows: 1) The high risk subgroups (incidence rate/100 person-years is more than
      6) were chronic Af with VHD or hypertension. The low risk subgroups (less than 2)
      were paroxysmal Af under 60 years of age, chronic Af with mitral valve prolapse
      syndrome or with hyperthyroidism. 2) There was no vulnerable period for
      occurrence of CVD during 9 years' follow-up from the onset of Af. 3) No
      significant difference in the incidence of CVD was seen in the groups with
      antiplatelet therapy and without.

PMID- 7500554
TI  - [Study of atherosclerosis regression in the elderly--central depression and its
      correlation to ulcerated plaques].
AB  - Atherosclerotic plaque with central depression (depressed lesion) was firstly
      proposed in our previous report as one of the morphological features of regressed
      lesions, which was characterized by the presence of isolated, well defined
      lesions with a centrally depressed area and smooth surface. They were obviously
      different from atherosclerotic plaques with ulceration (ulcerated plaques) in
      elderly autopsy cases. In this study, 30 ulcerated plaques obtained from
      specimens of the elderly aortas were histologically and immunohistochemically
      investigated to clarify the morphogenesis of the depressed lesion and its
      correlation to the ulcerated plaque. These depressed lesions were divided into 4
      groups according to their derivation; (a) fused lesion of multiple fibrous
      plaques, (b) regressing lesion of plaques, (c) healed ulcerated plaques, and (d)
      mixed type of these lesions. Regeneration of endothelial cell was noted in the
      peripheral zone of ulcerated plaques, and collagen type IV was also increased in
      the stroma of these ulcerated plaques. These were healed ulcerated plaques. The
      ulcerated plaques with complete restoration of endothelial cells on the ulcerated
      surface may become atherosclerotic plaques with central depression. These lesions
      are one of the histological features of regression in advanced atherosclerosis.

PMID- 7500556
TI  - [A case of chylothorax caused by mesenteric panniculitis].
AB  - A 76-year-old female was referred to our hospital for examination of milky
      pleural effusion. We diagnosed her illness as chylothorax because of the high
      concentration of triglyceride in the effusion. There was neither obstruction nor
      damage of the thoracic duct. Systemic evaluation disclosed an abdominal mass in
      the umbilical region. Fasting with intravenous hyperalimentation followed by
      pleurodesis with minocycline successfully eliminated the effusion. On the other
      hand, the abdominal mass was diagnosed as mesenteric panniculitis by open biopsy.
      Since she also had chylous ascites, the tumor could have obstructed the
      intestinal lymphatics. Chylothorax was probably caused by damage to collateral
      lymph circulation.

PMID- 7500557
TI  - President's message: we're starving our young.

PMID- 7500555
TI  - [A case of Binswanger's disease in which an acute infarcted lesion was detected
      by diffusion-weighted magnetic resonance imaging].
AB  - Diffusion-weighted magnetic resonance imaging (DWI) was carried out on a patient
      with Binswanger's disease suffering from acute cerebral infarction. Though an
      acute infarcted lesion was demonstrated as a high signal area on the T2-weighted
      image, it was impossible to determine whether it was acute or chronic because of
      extensive deep white matter lesions (periventricular hyperintensity and white
      matter hyperintensity lesions). However, only the acute infarcted lesion was
      detected on DWI which showed it as a high signal area, suggesting reduced
      molecular diffusion of water. The apparent diffusion coefficient (ADC), a
      physiological parameter that characterizes the self-diffusion on water in tissue,
      was lower in the acute lesion and higher in the chronic lesion. DWI can
      differentiate acute from chronic infarcts, which is not possible by conventional
      CT and MRI.

PMID- 7500558
TI  - On course for the future: the ENA Foundation endowment campaign.

PMID- 7500559
TI  - Iron poisoning: management tips on pediatric chewable multivitamin ingestion.

PMID- 7500560
TI  - Violence against nurses: what is the law?

PMID- 7500561
TI  - Gamma hydroxybutyrate overdose: two cases illustrate the unique aspects of this
      dangerous recreational drug.

PMID- 7500562
TI  - Evaluation of four methods of warming intravenous fluids.
AB  - OBJECTIVE: The purpose of this in vitro study was to compare four methods of
      warming intravenous fluid (IVF) with a control of unwarmed IVF at flow rates of
      200, 400, 600, 800, and 1000 ml/hr. DESIGN: A 5 x 5 factorial experimental design
      was used to evaluate the methods of warming IVF and the control at varied flow
      rates. METHODS: The methods of warming IVF in this study included the following:
      (1) the Level 1 System 250 fluid warmer with D-60HL tubing (Level 1 Technologies,
      Inc., Rockland, Mass.); (2) the Level 1 System 250 fluid warmer with D-50 tubing
      (Level 1 Technologies, Inc.); (3) the Hotline fluid warmer with L-70 tubing
      (Level 1 Technologies, Inc.); and (4) the Baxter DW 1000 D blood fluid warmer
      with blood cuff set tubing (Baxter Healthcare Corporation, Valencia, Calif.). The
      IVF temperatures were measured with thermocouples at three points: (1) in the
      intravenous solution bag, (2) in the tubing after the infusion pump, and (3) 2 cm
      proximal to the end of the tubing. Ambient temperature and the temperature at the
      three measurement points were recorded when the temperature at the point 2 cm
      proximal to the end of the tubing was stable for 3 minutes. RESULTS: With single
      lumen tubing, fluids flowing at low rates (e.g., 200 ml/hr) were barely warm at
      the end of the tubing. In contrast, fluid warmed with triple-lumen technology was
      consistently kept warm throughout the tubing.

PMID- 7500563
TI  - Identification of abuse in emergency departments: effectiveness of a two-question
      screening tool.
AB  - OBJECTIVE: A national health objective for the year 2000 is that at least 90% of
      hospital emergency departments have protocols for routine identification,
      treatment, and referral for victims of spouse abuse. An effective assessment tool
      is needed to implement such protocols. METHODS: To test the effectiveness of a
      two-question, nurse-administered, screening tool to detect physical abuse, 416
      black, Hispanic, and white women coming to public and private emergency
      departments with vaginal bleeding were asked two questions. Additionally, a 14
      item Danger Assessment Scale to determine risk factors of homicide was
      administered to all women. RESULTS: In response to the two-question abuse
      assessment screen, 38% of the 416 women reported a history of physical or sexual
      abuse. For 61% of the women, the last episode of abuse occurred within the last
      12 months. White women reported significantly more abuse than other ethnic groups
      (chi 2 = 18.71; df = 2; p = 0.00009). Teenagers reported more risk factors of
      homicide. DISCUSSION: Abuse to women who seek care in emergency departments is
      common and easily detected with a straightforward two-question screen. Universal
      assessment and accompanying information on safety and community resources is
      essential to interrupt abuse, prevent further trauma and potential homicide, and
      promote the health and safety of women.

PMID- 7500564
TI  - Use of hematocrit changes as an indicator of blood loss in adult trauma patients
      who receive intravenous fluids.
AB  - OBJECTIVES: To validate the use of changes in hematocrit as an indicator of blood
      loss in adult trauma patients receiving IV fluids and to identify parameters of
      hematocrit changes that may differentiate between patients with and without
      hemorrhage. DESIGN: A descriptive, retrospective chart review. SAMPLE/SETTING: A
      convenience sample of 90 adult trauma patients at an urban level I trauma center
      emergency department who received IV fluids for whom hematocrit measurements were
      available. METHODS: Records were reviewed for patients with documented hematocrit
      readings before and after receiving 2 L of IV fluid, noting the time between
      hematocrit measurements. Patients were divided into groups: Group 1 consisted of
      74 subjects with no hemorrhaging (< 500 ml blood loss); group 2 consisted of 16
      subjects in whom hemorrhage occurred (> 500 ml of blood loss). RESULTS: In group
      1 (nonhemorrhage group), the mean hematocrit change was -5.3%; in group 2
      (hemorrhage group) the hematocrit change was -8.3%. The findings showed a
      statistically significant difference (p < 0.05) between the groups for both the
      repeat hematocrit scores and the change in hematocrit scores. On the basis of a
      hematocrit decrease of 5% or less, 97% of the patients would have been correctly
      assigned to the nonhemorrhage group. CONCLUSION: Hematocrit determinations are a
      valid indicator of blood loss in trauma patients receiving IV therapy. The use of
      repeat hematocrit readings for clinicians trying to differentiate those with
      significant blood loss and the effects of IV fluid administration remains
      limited.

PMID- 7500565
TI  - Golden minutes: the Oklahoma City bombing--two ED nurses' stories.

PMID- 7500566
TI  - Using point-of-care testing to speed patient care: one emergency department's
      experience.

PMID- 7500567
TI  - Continuous 12-lead ST segment monitoring: an adjunct to identifying silent
      ischemia and infarct in the emergency department.

PMID- 7500568
TI  - "Fast tracking" ED patients with chest pain: integrating the chest pain
      evaluation unit and the observation unit.

PMID- 7500569
TI  - Alcohol and trauma in the emergency department.

PMID- 7500570
TI  - NSAIDs: what you don't know can hurt you.

PMID- 7500571
TI  - A look at our new emergency department: St. Mary's Health Center, St. Louis,
      Missouri.

PMID- 7500572
TI  - A new concept in emergency operations exercises: peer evaluation.

PMID- 7500574
TI  - EMS radio transmission form for ED use.

PMID- 7500573
TI  - Justifying the cost of an air medical transport (rotorcraft) program.

PMID- 7500575
TI  - An ED forensic kit.

PMID- 7500576
TI  - An emergency services nurse liaison program.

PMID- 7500577
TI  - Cost containment through inventory reduction.

PMID- 7500578
TI  - Using computer bulletin boards.

PMID- 7500579
TI  - Would you mind repeating that?

PMID- 7500581
TI  - A manuscript editor's wish list: or "go ahead, make my day (please)".

PMID- 7500580
TI  - Emergency department telephone advice.

PMID- 7500582
TI  - Fever care: does nursing instruction make a difference?

PMID- 7500584
TI  - Trauma center best practices.

PMID- 7500583
TI  - Sexual assault and multiple trauma: a sexual assault nurse examiner (SANE)
      challenge.

PMID- 7500585
TI  - A 3-month-old infant with seizures and decreased level of consciousness.

PMID- 7500586
TI  - Healing after Vietnam: Diane Carlson Evans' story. Interview by Laureen A Otto.

PMID- 7500587
TI  - Larry.

PMID- 7500588
TI  - My Florence Nightingale.

PMID- 7500589
TI  - Policy for utilizing do-no-hospitalize orders in Kansas.

PMID- 7500591
TI  - Legal implications of Alzheimer's disease.

PMID- 7500590
TI  - Angioplasty for myocardial infarction.

PMID- 7500592
TI  - History and the genome project.

PMID- 7500593
TI  - Assessing the social impact of human genome research: a status report.

PMID- 7500594
TI  - Genetic advances: influences on the delivery of health care.

PMID- 7500595
TI  - The new human genetics: ethical issues and implications for public policy.

PMID- 7500596
TI  - Ethics and the human genome project.

PMID- 7500598
TI  - A practical introduction to computers for the physician: computerizing the CME
      record.

PMID- 7500597
TI  - Balloon pulmonary valvuloplasty for isolated pulmonary valvular stenosis.
AB  - Fifteen balloon pulmonary valvuloplasties (BPVs) were performed on 13 infants and
      children with isolated pulmonary valvular stenosis (PVS). There were no
      complications. Two patients required repeat BPV, one for failure, the other for
      restenosis. At the time of the 13 latest BPVs, age ranged from three days to 13.1
      years (mean 5.7 +/- SD 4.8 years). Average Doppler pulmonary valve pressure
      gradient preceding BVP was 75 +/- 22 mm Hg. At follow-up it was 25 +/- 9 mm Hg (p
      < .0001). Follow-up interval was 0.61 to 4.70 years (2.29 +/- 1.18). Restenosis
      occurred in 1/13 (8%) of the patients. The remaining 12/13 (92%) showed highly
      satisfactory sustained gradient reductions. Doppler gradients preceding BPV by as
      much as 4 months correlated highly with catheter gradients at time of BPV,
      confirming that Doppler echocardiography is a highly accurate indication of PVS
      severity. Catheterization for PVS should therefore not be used for diagnostic
      purposes alone. BPV can be performed safely, economically and effectively and is
      recommended as the treatment of choice for infants and children with moderate to
      severe isolated PVS. For very young patients, follow-up Doppler surveillance
      should be done semi-annually; for all others, annually.

PMID- 7500599
TI  - A swimming-pool-associated outbreak of cryptosporidiosis.

PMID- 7500600
TI  - HIV survey of childbearing women in Kansas, 1992-1994.

PMID- 7500601
TI  - [Effect of various therapeutic protocols on growth and final height of children
      with acute lymphoblastic leukemia or non-Hodgkin's lymphoma].
AB  - A total of 74 children suffering from acute lymphoblastic leukaemia (ALL) or non
      Hodgkin lymphoma (NHL) were involved in a retrospective analysis of their
      physical growth during and after the therapy. Out of this total number, 54
      children were subjected to radiochemotherapy in compliance with the VII/(81)
      scheme, and another 20 children in compliance with the LSA2L2 scheme. At the
      beginning of the therapy the average height-standard deviation score (H-SDS) for
      both groups of patients corresponded with the population average. The patients
      subjected to the VII/(81) scheme showed, throughout the observation period of
      five years from the beginning of the therapy, a height normal for their age
      group. Contrary to this observation, the patients subjected to the LSA2L2 scheme
      experienced a significantly different growth in the period under observation and
      continually lost height in comparison to the normal population. The same results
      were experienced with a smaller group of patients whose growth was followed up
      for eight years from the beginning of therapy. 16 patients (VII/81 n = 4/LSA2L2 n
      = 12) reached their final height. For the patients of the VII/(81) scheme the
      final height showed an average H-SDS of 0.27 and for the patients of the LSA2L2
      scheme of -1.22 (p = 0.068). Considering that the same cranial radiotherapy (max.
      18 Gy for both schemes) and a comparable intensive induction therapy were
      applied, it must be concluded that the intensity and duration of the maintenance
      treatment are the critical factors initiating a different growth behaviour of the
      two groups subjected to radiochemotherapeutical schemes.

PMID- 7500602
TI  - [X-chromosome recessive lymphoproliferative disease (XLP): molecular genetic
      studies].
AB  - X-linked lymphoproliferative disease (XLP) is a rare worldwide occurring
      inherited immunodeficiency which is triggered by Epstein-Barr virus infection.
      Clinical phenotypes in 21 affected males from 5 German families with XLP ranged
      from severe and fatal infectious mononucleosis (57%) to acquired
      hypogammaglobulinaemia (28%), malignant lymphoma (28%), aplastic anaemia (19%)
      and hypergammaglobulinaemia M (19%). Molecular genetic studies with various
      polymorphic X-chromosomal DNA markers in 14 XLP families mapped the XLP gene
      locus to Xq25-q26. Haplotype analysis enables detection of XLP-positive and XLP
      negative males already before EBV-infection as well as diagnosis of healthy
      female carriers within XLP families.

PMID- 7500603
TI  - [The microagglutination test--a simple and sensitive procedure for serodiagnosis
      of pertussis infections].
AB  - The microagglutination assay is a useful method for the diagnosis of B. pertussis
      infections. In a group of 30 patients with culture proven pertussis 27 (90%) had
      > or = fourfold increases in titers between acute and convalescent phase serum
      specimens. The microagglutination test offers several advantages over other more
      sophisticated B. pertussis antibody tests: only 50 microliters of serum is
      required, it is a standardized test, which doesn't require specialized technical
      expertise or equipment, it is easy to perform and good results are noted in a
      broad age range of patients. Disadvantages of the microagglutination test are:
      two separate serum specimens are necessary (acute and convalescent phase), the
      test does not differentiate IgA and IgG antibodies and the temporal association
      with recent immunization can lead to false positive results. In our opinion the
      microagglutination test is a useful method for the diagnosis of B. pertussis
      infections. This is especially true in cases where more sophisticated serologic
      tests such as ELISA can not be performed immediately but physicians and patients
      expect to get a result quickly.

PMID- 7500604
TI  - [Spontaneous growth of children with chronic renal failure].
AB  - Several pathogenetic factors may contribute to the growth failure in patients
      with CRF. We have analysed retrospectively spontaneous growth in 30 patients with
      CRF and investigated the influence of various therapies (conservative therapy,
      hemodialysis and transplantation with different immunosuppressive therapy) on
      spontaneous growth. At diagnosis (age 8.5 +/- 0.8 years; mean +/- SEM) height was
      reduced in the whole group (-1.46 +/- 0.2 SDS; x +/- SEM). Height SDS decreased
      further during the observation period of two and three years in the hemodialysis
      group (-2.19 +/- 0.69) and in the group with conservative treatment (-2.58 +/-
      0.93), respectively. After Tx (n = 26) patients received different types of
      immunosuppressive therapy: 18 patients received cyclosporin A and prednisone (4-6
      mg/m2 BS) daily; 8 transplanted patients received azathioprine (2 mg/kg BW)
      additionally. After Tx height improved not significantly (-2.02 +/- 0.30 vs. 
      1.49 +/- 0.36 SDS and -2.52 +/- 0.64 vs. -2.05 +/- 0.24 SDS after three and two
      years, respectively) irrespective of the immunosuppressive therapeutic regime. In
      the whole patient group neither hemodialysis nor conservative treatment nor Tx
      caused a significant change in height SDS; the possible factors, that might be
      involved in growth failure, are discussed.

PMID- 7500605
TI  - [5-aminosalicylic acid and chronic inflammatory bowel diseases in children].
AB  - 5-Aminosalicylate (mesalazine; 5-AS) represents a new therapeutic strategy in
      chronic inflammatory bowel disease. The drug (active metabolite of sulfasalazine)
      has proven its clinical efficacy and safety in numerous controlled studies in
      adults. However only limited data are available for the pediatric population.
      This brief review summarises the published spares information on this promising
      agent. As pharmacokinetic properties of 5-AS are age-independent and since 5-AS
      has a wide margin of safety clinical studies and use of this drug should be
      encouraged also in children.

PMID- 7500606
TI  - [Schimmelpenning-Feuerstein-Mims syndrome and its neurologic manifestations. 6
      personal cases and review of the literature].
AB  - The Schimmelpenning-Feuerstein-Mims-syndrome includes deformities and dysplasias
      of the skin, eyes, brain, skeleton, and heart. It may result from a malformation
      of the ectodermal and mesodermal blastoderm in the third week of gestation. We
      here report on 6 patients who presented between 1977 and 1993 in comparison with
      those cases in the literature. All children presented neurologic symptoms. The
      major symptom was a linear epidermal nevus. In addition we found mental
      retardation, convulsions, asymmetries of the cranial structures or dilated
      cerebral ventricles ipsilateral to the nevus. One child had a defect of the skull
      and scalp, a symptom not previously mentioned in the literature. Our patients
      exhibited a wide phenotypice spectrum ranging from mild to severe forms. Severe
      neurological symptoms were also found in patients despite minimal dermal
      involvement.

PMID- 7500607
TI  - [Osteosarcoma in 2 siblings. A case report].
AB  - With a brother and sister, osteosarcoma developed at the age of 11 and 14
      respectively. With both there was no previous retinoblastoma or other bone
      disease with a proclivity to develop osteosarcoma. We discuss possible
      explanations for familial aggregation of osteosarcoma, citing external or genetic
      factors. We suggest that it is the retinoblastoma gene RB and the tumor
      suppressor gene p53 which play an important part in the development of
      osteosarcoma.

PMID- 7500609
TI  - [Dwarfism in pericentric inversion of the X-chromosome].
AB  - We report on a 9 2/12 year old girl with pericentric inversion of the X
      chromosome. It was diagnosed accidentally by a chromosome-analysis led through
      because of small stature. She bears a strong phenotypic resemblance to her mother
      (normal chromosomes), carrier of the pericentric inversion however is the
      phenotypically normal father. The breakpoint of the X-chromosome not lying within
      the critical region suggests that the patient will neither suffer a gonadal
      dysfunction. Both short stature and phenotypic dysmorphic features have familial
      cause.

PMID- 7500608
TI  - [Pulmonary lymphangiectasis with spontaneous chylothorax in Noonan syndrome].
AB  - We report a case of Noonan syndrome associated with pulmonary stenosis and major
      lymphedema of the lower extremities. At the age of 15 yr spontaneous chylothorax
      with increasing dyspnea occurred> Chest-x-ray demonstrated increased interstitial
      markings restricted to the right lower lobe representing pulmonary
      lymphangiectasia. The chylothorax did not respond to repeated thoracocentesis and
      medium-chain-triglyceride diet. When a chest tube was inserted and total
      parenteral nutrition was supplied, the chylous effusion decreased within 32 days.
      The patient is still on diet and asymptomatic effusion remained during 12 months
      follow up. In conclusion, pulmonary lympgangiectasia should be considered in
      patients with Noonan syndrome and an abnormal interstitial pulmonary pattern
      similar to pulmonary congestion (without any hemodynamic abnormalities). In case
      of pleural effusion, chylothorax should be considered.

PMID- 7500610
TI  - [Neuralgic shoulder amyotrophy as differential diagnosis of scapula alata].
AB  - We describe two patients with neuraligic amyotrophia of the shoulder: a 15 year
      old boy and a girl which was 6 years old at the time of primary manifestation.
      Mostly adolescent patients are concerned. Beginning is acute, the etiology
      unclear. The patients initially feel intensive pain in one shoulder, which
      typically is followed by motorical weekness of the proximal upper arm and the
      shoulder. Nearly all patients reach a restitutio ad integrum after some months.
      As differential diagnosis we have to take into account the facio-scapulo-humeral
      muscular dystrophy, pareses of single or various nerves or a neurititis of
      infectious origin.

PMID- 7500611
TI  - Quantitative determination of codeine and its major metabolites in human hair by
      gas chromatography-positive ion chemical ionization mass spectrometry: a clinical
      application.
AB  - A highly sensitive method was developed for the quantitative analysis of codeine
      and morphine in human hair. After addition of deuterated internal standards, hair
      samples were digested overnight in 1N NaOH at 37 degrees C. Hydrolysis was
      performed on certain digests by addition of 1 mL 6N HCl. Digest solutions were
      extracted using a solid-phase procedure with Bond Elut Certify extraction
      columns. Derivatized extracts were analyzed on a Finnigan ion trap mass
      spectrometer (Magnum) in the positive ion chemical ionization mode using acetone
      as the reagent gas, helium as the carrier gas, and a DB-5 MS (30 m x 0.25-mm
      i.d.) capillary column. The assay was linear to 75 ng/mg (r = 0.99) and was
      capable of detecting 10 pg of codeine and morphine on-column. Intra-assay
      precision ranged from 8 to 20%. The method was used to quantitate codeine in
      human hair obtained from two male volunteers with dark brown to black hair after
      a single oral dose of 120 mg codeine phosphate liquid. Hair samples were plucked
      from the scalp for 28 days and then cut at the scalp. Codeine was detectable in 1
      cm long hair (containing the bulb) at 12 h following the dose and remained
      detectable in the hair shaft for at least 8 weeks. Codeine metabolites were not
      detected in the hair of these two subjects. The method is currently being used in
      dose-response disposition studies to quantitate codeine and its major metabolites
      in human subjects.

PMID- 7500612
TI  - Storage temperature effect on the stability of morphine and codeine in urine.
AB  - Urine samples collected from one laboratory volunteer and five alleged heroin
      addicts are prepared (without preservatives) in 5-mL aliquots in glass culture
      tubes and stored at room, refrigerator, and freezer temperatures. Total morphine,
      total codeine, free morphine, and free codeine in these samples are analyzed at
      30-day intervals for an 11-month period. Total morphine and total codeine
      concentration decreases are observed for all specimens in all storage conditions.
      For samples stored in the refrigerator and freezer, similar concentration
      decrease patterns are observed for total morphine and total codeine, and the
      decreases range from approximately 10 to 40%. The concentrations of free morphine
      and free codeine show slight but steady increases. For samples stored at room
      temperature, large decreases of total morphine are observed for three out of 10
      specimens, and total codeine and total morphine concentrations (in seven other
      specimens) show a decrease pattern similar to that observed for the freezer and
      refrigerator storage conditions. Three concentration change patterns are observed
      for free morphine: The type I pattern follows the same decrease pattern observed
      for freezer and refrigerator storage conditions; the type II pattern shows free
      morphine increases (after 30-90 days of storage) that remain relatively high for
      the entire 11-month period; and the type III pattern shows initial increases,
      followed by gradual decreases to levels that are comparable with the specimens'
      respective initial concentrations. Free codeine concentrations show slight and
      steady increases for the entire 11-month period in all specimens.

PMID- 7500613
TI  - Evaluation of the Abbott TDx serum benzodiazepine immunoassay for the analysis of
      lorazepam, adinazolam, and N-desmethyladinazolam.
AB  - This study involved the evaluation of the Abbott TDx serum benzodiazepine assay,
      a fluorescence polarization immunoassay (FPIA), for the detection of lorazepam,
      adinazolam, and N-desmethyladinazolam in serum. Precision of the assay was
      determined by using three control serums containing 75, 300, and 700 ng/mL
      nordiazepam. Between-run precision studies (N = 22) gave mean values of 76, 306,
      and 690 ng/mL with coefficients of variation of 6.5, 3.3, and 5.7%, respectively.
      Percent cross-reactivity of serum lorazepam standards (35-500 ng/mL) ranged from
      29 to 69%. The cross-reactivity of serum adinazolam ranged from 40 to 47% between
      50 and 150 ng/mL and from 38 to 55% for N-desmethyladinazolam between 50 and 250
      ng/mL. Serum specimens (48) collected from individuals known to be receiving
      lorazepam were analyzed. Twenty-two specimens were positive for benzodiazepines.
      Serum specimens were collected from 0.25 to 24 h after administering a 15-mg oral
      dose of adinazolam to six volunteers. The FPIA results were compared with
      combined high-performance liquid chromatographic (HPLC) results for adinazolam
      and N-desmethyladinazolam. The FPIA method did not detect benzodiazepines at 0.25
      h after administration of adinazolam but did detect benzodiazepines from 0.5 to
      24 h after administration. The correlation between HPLC (N-desmethyladinazolam)
      and FPIA results by regression analysis gave the following: y = 0.937x + 4.449, r
      = 0.98, n = 15. It was concluded that the Abbott FPIA assay for benzodiazepines
      can detect lorazepam when prescribed in therapeutic doses and when present at
      greater than 25 ng/mL and can semiquantitatively detect adinazolam or N
      desmethyladinazolam or both when present at concentrations greater than 50 ng/mL.

PMID- 7500614
TI  - Cannabinoids in humans. I. Analysis of delta 9-tetrahydrocannabinol and six
      metabolites in plasma and urine using GC-MS.
AB  - This report describes a method for the quantitative analysis of delta 9
      tetrahydrocannabinol and six of its metabolites, 8 alpha-hydroxy-delta 9
      tetrahydrocannabinol, 8 beta-hydroxy-delta 9-tetrahydrocannabinol, 11-hydroxy
      delta 9-tetrahydrocannabinol, 8 alpha,11-dihydroxy-delta 9-tetrahydrocannabinol,
      8 beta,11-dihydroxy-delta 9-tetrahydrocannabinol, and 11-nor-9-carboxy-delta 9
      tetrahydrocannabinol. In addition, the method was designed to detect cannabidiol
      and cannabinol, two naturally occurring cannabinoids. Plasma and urine samples
      were hydrolyzed with bacterial (Escherichia coli) beta-glucuronidase and
      extracted with hexane-ethyl acetate (7:1). Analysis and quantitation were
      performed by gas chromatography-mass spectrometry in the electron ionization mode
      coupled with selected ion monitoring. The cannabinoids were detected as their
      trimethylsilyl derivatives to enhance their chromatographic separation and mass
      spectral characteristics. The linearity of the procedure was excellent for all of
      the compounds within the range tested (0-100 ng/mL). Limits of detection ranged
      from 0.5 to 1.5 ng/mL in urine and from 0.6 to 2.1 ng/mL in plasma depending on
      the analyte.

PMID- 7500615
TI  - Cannabinoids in humans. II. The influence of three methods of hydrolysis on the
      concentration of THC and two metabolites in urine.
AB  - Glucuronide conjugates of cannabinoids were previously identified in humans. For
      gas chromatographic-mass spectrometric (GC-MS) analysis of the unconjugated
      compounds in human urine, it is necessary to cleave the glucuronide moiety. Base
      hydrolysis and two forms of enzymatic hydrolysis were compared in this study to
      examine any quantitative differences between the hydrolysis methods. Human
      volunteers (n = 8) each smoked one marijuana cigarette containing 3.58% delta 9
      tetrahydrocannabinol (THC) and submitted urine samples prior to smoking, 5 min
      after smoking, and hourly for 8 h thereafter. Urine (1 mL) was buffered to the
      optimum pH for each form of enzyme tested. beta-Glucuronidase from Escherichia
      coli (bacteria) or Helix pomatia (mollusk) was added to the specimens, followed
      by overnight incubation at 37 degrees C. Following hydrolysis, the samples were
      extracted using hexane-ethyl acetate (7:1) and derivatized with N,O
      bis(trimethylsilyl)-trifluoroacetamide plus 1% trimethylchlorosilane, which
      converted the cannabinoids to their trimethylsilyl derivatives. GC-MS analysis
      revealed striking differences between the hydrolysis methods. Concentrations of
      unconjugated THC and 11-hydroxy-THC (11-OH-THC) using E. coli were significantly
      increased over all other methods tested (p < .05). These results demonstrate the
      species-dependent nature of glucuronidase activity in hydrolyzing THC and 11-OH
      THC glucuronides and the ineffectiveness of base hydrolysis on these hydroxylated
      compounds. The need for further study to find the optimum conditions necessary
      for the complete hydrolysis of cannabinoid conjugates is suggested.

PMID- 7500616
TI  - Facilitation of thin-layer chromatographic identification of opiates by
      derivatization with acetic anhydride or methoxyamine.
AB  - Qualitative identification of opiates in urine is commonly achieved in two
      stages, the first involving immunoassay screening and the second involving
      chromatographic confirmation. Identification of specific opiates is often
      requested to determine whether the source of opiates is from diet, prescription
      pharmaceuticals, or illicit drugs. During evaluation of the Toxi-Lab thin-layer
      chromatographic system as a confirmatory technique for urinary opiates, we
      encountered difficulty distinguishing opiates with similar retention factor
      values and colorimetric behavior. By exploiting chemical differences of the
      comigrating opiates through preparation of acetate or methoxime derivatives,
      followed by chromatography of the underivatized and derivatized samples in
      adjacent lanes, we were able to more easily distinguish codeine from hydrocodone,
      6-acetylmorphine from oxymorphone, and dihydrocodeine from hydromorphone.

PMID- 7500617
TI  - Comparison between GC-MS and the EMIT II, Abbott ADx, and Roche OnLine
      immunoassays for the determination of THCCOOH.
AB  - Gas chromatography-mass spectrometry (GC-MS) and immunological methods, including
      the Syva enzyme multiplied immunoassay technique, the Abbott fluorescence
      polarization immunoassay, and the Roche OnLine immunoassay, were compared for the
      determination of 11-nor-delta 9-tetrahydrocannabinol-9- carboxylic acid
      (THCCOOH). The results of all three immunoassays were not in accordance with the
      GC-MS results in three cases of a 72-specimen panel. Only one false negative was
      observed using the OnLine immunoassay. The immunological methods compared
      favorably and are acceptable for detecting the presence of cannabis metabolites
      in urine. These results support the concept that all immunoassays for
      cannabinoids should be considered as screening procedures. No concentration
      correlation between GC-MS and the immunoassays could be established because of
      the different cross-reactivities of the metabolites.

PMID- 7500618
TI  - Postmortem tissue samples: an alternative to urine and blood for drug analysis in
      racehorses.
AB  - Although urine is the sample of choice for drug tests in racehorses, it is rarely
      obtained following the sudden death of a racehorse on the track while racing. The
      purpose of this study was to demonstrate the significance of postmortem tissue
      samples as an alternative to urine and blood samples in equine drug analysis
      following the sudden death of a racehorse on the track while participating in a
      competitive race. Postmortem tissue samples were frozen (-80 degrees C) until
      analyzed. A 30-40-g portion of each organ was homogenized in a 0.1 M phosphate
      buffer (pH 7.4), deproteinized, hydrolyzed with beta-glucuronidase, extracted,
      and screened by thin-layer chromatography and immunoassay. Samples that initially
      tested positive for drug(s) were then extracted using high-flow, solid-phase
      extraction cartridges. The eluates were analyzed by gas chromatography-mass
      spectrometry. The presence of butorphanol in horses HB355 and CD387,
      pentobarbital in horse HO940, and ergotamine in horses HO940 and CD387 was
      detected and confirmed. Thus, in the absence of urine and blood samples following
      sudden death, postmortem tissue samples are equally useful for forensic
      toxicological investigations of racehorses.

PMID- 7500619
TI  - Rapid GC-MS confirmation of urinary amphetamine and methamphetamine as their
      propylchloroformate derivatives.
AB  - Amphetamine and methamphetamine are extracted from 200 microL of urine into an
      organic solvent containing propylchloroformate. The amines immediately react to
      form propylcarbamate derivatives. The aqueous phase is removed, and a portion of
      the organic phase is analyzed by gas chromatography-mass spectrometry. Either the
      deuterated analogues or N-propylamphetamine internal standards give acceptable
      results. For day-to-day precision, coefficients of variation in the range of 6
      10% are found. The method is linear to 10,000 ng/mL. Limits of quantitation and
      detection are 50 and 5 ng/mL, respectively, when using N-propylamphetamine as the
      internal standard. Extracts are stable at room temperature for at least 60 days.
      There is no interference from other amphetamine drugs.

PMID- 7500620
TI  - Determination of pesticide metabolites in human urine using an isotope dilution
      technique and tandem mass spectrometry.
AB  - A method that measures 12 analytes in urine and reflects possible exposure to
      pesticides was developed. The sample preparation involves enzyme hydrolysis and
      solvent extraction through the use of laboratory robotics, followed by phase
      transfer catalysis derivatization and silica cleanup. Samples are analyzed by
      capillary gas chromatography and tandem mass spectrometry using an isotope
      dilution technique with 13C-labeled internal standards. The limit of detection is
      1 microgram/L (1 part per billion) for most analytes, and most analytes have a
      linear response up to 100 micrograms/L. The precision of the method is reflected
      in the variation observed in quality control materials over 33 months; the
      variation averaged 17% for these analytes. On the basis of the detectable analyte
      levels of unspiked urine samples collected from unexposed volunteers, this method
      can be used to measure the low levels necessary for establishing reference range
      values of the selected pesticides or metabolites.

PMID- 7500622
TI  - Drug concentrations in human hair after bleaching.

PMID- 7500621
TI  - Analysis of 11-nor-delta-9-THC-carboxylic acid in meconium with immunoassay and
      HPLC diode-array detection.

PMID- 7500623
TI  - Assessment of aerobic and anaerobic demands of dinghy sailing at different wind
      velocities.
AB  - The aim of this study was to assess the oxygen uptake (VO2), heart rate (HR) and
      blood lactate concentration ([Lab]) during actual dinghy sailing at different
      wind velocities. Eight top class Laser sailors volunteered to participate in the
      study. In the laboratory, each subject performed an incremental exercise test on
      a cycle ergometer to the point of exhaustion. Maximum oxygen uptake (VO2max) and
      maximum heart rate (HR max) were assessed by means of a Cosmed K2 (K2) portable
      oxygen analyser while the accuracy of the K2 was simultaneously examined by
      comparing it with the Douglas bag method. On water each subject underwent a 10
      minute continuous upwind sailing test. The average percentages of VO2max and HR
      max during sailing and the post-test [La(b)] were 39 +/- 6%, 74 +/- 11% and 2.3
      +/- 0.8 mM, respectively. Values of the three measured variables for each subject
      were significantly correlated to wind velocity (r = 0.73, 0.87 and 0.88,
      respectively). The results of the study suggest that the metabolic and
      cardiorespiratory demands of dinghy sailing predominantly depend on the wind
      conditions. Aerobic capacity is only moderately taxed in dinghy sailing and
      should not be emphasized in training, whereas anaerobic metabolism plays an
      increasing role in stronger winds.

PMID- 7500624
TI  - Muscular endurance repetitions to predict bench press strength in men of
      different training levels.
AB  - The purpose of this study was to determine the accuracy of predicting maximal
      bench press (BP) strength (1-RM) from relative endurance performance in various
      groups of men. The subjects included untrained students (n = 35), resistance
      trained students (n = 28), college wrestlers (n = 21), soccer players (n = 22),
      football players (n = 51), high school students (n = 35), and resistance-trained
      middle-aged men (n = 24). Each subject performed a 1-RM test according to the
      same standard procedure. Within 4-10 days, the subject selected a weight to
      perform as many repetitions as possible to failure. Six relative endurance
      prediction equations produced validity coefficients of r = 0.86 to 0.98 in each
      group and r = 0.82 to 0.98 in the composite group (n = 220). In subjects
      completing < or = 10 repetitions-to-failure, three equations significantly
      overpredicted and two significantly underpredicted 1-RM scores. The Brzycki
      equation was the most accurate. In subjects completing > 10 repetitions to
      failure, three equations significantly overpredicted and three significantly
      underpredicted 1-RM scores. While caution should be used when employing relative
      muscular endurance performance to estimate 1-RM strength in the bench press, the
      average of two equations may reduce the error.

PMID- 7500625
TI  - Pulmonary gas exchange in athletes with exercise-induced hypoxaemia.
AB  - Hypoxaemia that is induced by physical exercise (EIH) in some athletes, who are
      however capable of enduring intense muscolar work, is a phenomenon that has been
      known for some time. However, assumptions such as alveolar hypoventilation, veno
      arterial shunt, limitation of diffusion, or mismarch of the VA/Q ratio, have not
      to date been able to exhaustively explain this phenomenon. In this study five
      athletes displaying exercise-induced hypoxaemia were evaluated by increasing-load
      exercise tests, as proposed by other authors, and by means of intermittent tests
      with supermaximal exercise steps (130% VO2 max) with breaks for incomplete
      recovery (3 min). The fundamental fact arising from our study is that the
      intermittent tests did not bring about hypoxaemia in the tests subjects. Analysis
      of the ventilator and metabolic parameters, of the alveolar pressure of the O2,
      and of the partial pressures of the CO2 in the arterial blood, all measured
      during the two different types of muscular exercise, lead to the belief that the
      different distribution of the pulmonary blood flow, which has been documented in
      highly trained athletes, plays a very important role in inducing EIH.

PMID- 7500626
TI  - Spontaneous pneumothorax in weightlifters.
AB  - Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our
      knowledge there has only been one case of spontaneous pneumothorax associated
      with weightlifting reported in the medical literature. We describe three
      consecutive cases of spontaneous pneumothorax associated with weightlifting. We
      postulate that spontaneous pneumothorax in these patients may be secondary to
      improper breathing techniques. It is important that physicians and weight
      trainers be aware of the association between weight lifting and spontaneous
      pneumothorax and assure that proper instruction is given to athletes who work
      with weights.

PMID- 7500627
TI  - Ankle systolic blood pressure following sub-maximal and maximal exercises in
      healthy young men.
AB  - Although recent studies have compared the effect of progressive exercise tests to
      constant moderate work load tests on ankle systolic blood pressure (ASBP) and
      ankle to arm index (AAI) in claudicants, little is known about the relation of
      ASBP and AAI to work load in healthy young men. Fifteen normal volunteers were
      asked to cycle 40, 60, 80, 100% of VO2max. Ankle and humeral pressures were
      recorded simultaneously, at rest and 1 minute after the end of each test.
      Thereafter, AAI was calculated as the ratio of ankle to humeral systolic
      pressure. Compared to resting values: 134.8 +/- 13.9 mmHg, ASBP increased
      significantly following sub maximal tests up to 157.8 +/- 28.1 mmHg (p < 0.005),
      but was not increased following maximal exercise: 141.5 +/- 28.2 mmHg (NS). On
      the other hand, AAI showed a progressive decrease from 1.14 +/- 0.06 at rest to
      1.06 +/- 0.08 (p < 0.005), but 0.98 +/- 0.07 (p < 0.005), to 0.84 +/- 0.06 (p <
      0.005) and to 0.75 +/- 0.09 (p < 0.005) following 40, 60, 80 and 100% of VO2max
      respectively. In summary, AAI following exercise is inversely related to workload
      whereas ASBP is not. We suggest that when studying ankle systolic blood pressure
      response to heavy load exercises, results should always be compared to humeral
      pressure, and expressed as ankle to arms indexes.

PMID- 7500628
TI  - Lipoprotein(a) and exercise.
AB  - Plasma levels of lipoprotein(a), total cholesterol, triglycerides, HDL
      cholesterol, LDL cholesterol, apoprotein A1 and apoprotein B were assessed in 10
      healthy, untrained volunteers subjected to a bicycle ergometric exercise equal to
      50% of individual VO2max, followed by increasing loads until muscular exhaustion.
      Blood samples were taken before the exercise, immediately afterwards and then at
      12-hourly intervals for a 72 hours period. Subsequently, the same parameters were
      evaluated for 8 long-distance runners during the XXIII New York Marathon, with
      blood samples being taken before and after the race, and then after one month of
      detraining. After the exercise, lipoprotein(a) in untrained subjects began to
      decrease significantly from the 24th hour on and remained lower than baseline
      levels up till the 72nd hour. After detraining, lipoprotein(a) in marathon
      runners increased significantly both with respect to basal values and especially
      to post-race values. Modifications of the other metabolic parameters evaluated in
      both tests were negligible and predictable. In the two groups of subjects
      examined, no correlation was found between lipoprotein (a) and the
      anthropometrical data and metabolic parameters considered.

PMID- 7500629
TI  - Dynamic muscle strength as a predictor of bone mineral density in elderly women.
AB  - Although muscle strength has been shown to predict bone mineral density (BMD) in
      older adults, the variance explained by isometric and isokinetic testing has been
      generally low (< 20%) and limited to only a few exercises and muscle groups. To
      elucidate the relationship of muscle strength to BMD at multiple sites, and to
      ascertain the most robust predictor of BMD using isotonic strength testing
      apparatus, we examined dynamic muscle strength and BMD in 40 healthy elderly
      women aged 65-82 years. BMD of the spine (L2-4), proximal femur (neck,
      trochanter, Ward's triangle), forearm (midradius), and whole body were measured
      by dual-energy X-ray absorptiometry. Dynamic strength (1-RM), utilizing isotonic
      weight-lifting equipment, was assessed for 10 standard upper and lower body
      exercises. In stepwise multiple regressions, leg press was the only independent
      predictor of spine (R2 = 0.11), neck and trochanter (R2 = 0.21 and 0.18), forearm
      (R2 = 0.21), and whole body BMD (R2 = 0.19), while bench press was an independent
      predictor of Ward's BMD (R2 = 0.12). The most robust predictor of regional and
      whole body BMD using isotonic equipment was the leg press, which may reflect
      overall skeletal health in this population. The portion of variance explained by
      dynamic muscle strength (11-21%) is similar to that reported when strength is
      assessed by isometric and isokinetic testing. The relationship of dynamic
      strength to BMD was not generally site-specific.

PMID- 7500630
TI  - Tarsal tunnel syndrome with double causes (ganglion, tarsal coalition) evoked by
      ski boots. Case report.
AB  - We report a 19-year-old female with tarsal tunnel syndrome arising from a
      ganglion and a bony prominence from talocalcaneal coalition. However, in this
      case, tarsal tunnel syndrome was caused by ski boots compressing the tibial nerve
      within the tarsal tunnel. The patient was successfully treated by surgery. This
      is believed to be the first case with double causes (ganglion, tarsal coalition)
      evoked by trauma (skiing).

PMID- 7500631
TI  - Structural and non-structural disease underlying high-risk cardiac arrhythmias
      relevant to sports medicine.
AB  - Problems of arrhythmogenic sudden death (ASD) in athletes have been re-assessed
      on the clinicopathological plane, encompassing the emerging, unsolved, question
      of so-called idiopathic ventricular tachycardia, and its debated diagnostics
      versus arrhythmogenic right ventricular dysplasia-cardiopathy. Ischemic
      infarction ASD from coronary artery pathology in young athletes has been seen to
      present with atherosclerotic "soft" subintimal plaques, rich in newly formed
      smooth myocytes, often attended by adventitial mast cell, as suspect microscopic
      markers of spasm, relevant to reperfusion; these features can be found also in
      precociously intramural arteries, responsible for ASD. Rare congenital
      abnormalities of the coronary ostia occasionally underlie ASD, together with the
      acquired aneurysmic coronaritis of chronic Kawasaki disease. Ischemic ASD can
      also be due to coronary arteriolopathy attending hypertrophic cardiomyopathy, a
      not uncommon disease in athletes, to be carefully discriminated from training
      heart hypertrophy. Young South-American sportsmen with Chagas' chronic
      cardiopathy seem to be at particular risk of ASD. Minor, but specific
      arrhythmogenic cardiac malformations such as accessory AV pathways have been
      detected in athletes succumbing to otherwise unexplained ASD, undergone careful
      post-mortem investigation. The need of more attentive and extended
      histopathologic control emerges from the hitherto ignored cardiac
      neuropathological substrates of reflexogenic ASD, which is cogent to problems of
      ASD in competing athletes. The thorough examination of the cardiac vascular
      centers in the brain stem, and of the peripheral cardiac innervation, at either
      abutments of the arc of dive- and/or Bezold-Jarisch cardioinhibitory
      vasodepressor reflex, made it possible to suggest novel clinicopathological
      explanations in controversial cases of athletes' ASD, safeguarding from grave
      leval misjudgements due to sport's forensic medical mistakes.

PMID- 7500632
TI  - The stages of exercise scale and stages of exercise behavior in female adults.
AB  - Using the Transtheoretical Model of behavior change as a theoretical framework, a
      Stage of Exercise Scale (SOES) was developed. The ability of the SOES to
      differentiate between subjects classified into each of the theoretically posited
      stages was then studied in a sample of 178 female adults. Results showed that the
      scale was able to significantly and meaningfully differentiate between subjects
      classified by stage in terms of exercise energy expenditure (p < 0.0001, omega 2
      = 0.18), physical activity energy expenditure (p < 0.0001, omega 2 = 0.15), and
      VO2peak ml/kg/min (p < 0.0001, omega 2 = 0.19). Stage-specific interventions have
      been successful when applied to other health behaviors and would appear to have
      promise for increasing our understanding of the exercise initiation and
      maintenance process. As such, researchers and practitioners may wish to use the
      SOES to begin testing the efficacy of stage-specific physical activity
      interventions.

PMID- 7500633
TI  - Metabolic and ventilatory responses to submaximal and maximal exercise using
      different breathing assemblies.
AB  - This study compared ventilatory and metabolic responses during exercise using
      three breathing assemblies: mouthpiece/noseclip (BV); mouth/face mask (MM); and
      facemask (FM). Ten male runners completed three maximal treadmill tests with
      breathing assembly randomly assigned. Metabolic and ventilatory data were
      recorded every 15s, and heart rate (HR) and rating of perceived exertion (RPE)
      each min. No significant differences were found for treadmill run time, HRmax,
      respiratory exchange ratio (RER), and RPE, indicating similar efforts on all
      trials. No significant differences were found at maximal exercise for VO2 minute
      ventilation (VE), tidal volume (VT), and breathing frequency (f). At ventilatory
      threshold (TVENT), VO2, VE, and f were not significantly different. However, peak
      flow (PF) was significantly higher for BV than FM, and VT was significantly
      higher for BV than MM and FM. Results indicate alterations in ventilatory
      mechanics occur at TVENT, but type of breathing assembly does not significantly
      affect maximal values.

PMID- 7500634
TI  - Effects of time of day on self-paced performances of prolonged exercise.
AB  - Pre-exercise body temperature varies throughout the day due to its circadian
      rhythm. This study aimed to compared responses to sustained exercise in the
      morning and in evening. Rectal temperature was measured pre-exercise and
      throughout a 60 min test on a cycle ergometer against a fixed frictional
      resistance in seven males (aged 19-24 years). The subjects were instructed to
      work as hard as possible over the entire exercise period but could vary the pedal
      frequency at any time. Power output was calculated by computer, utilising an
      optical detection device to monitor flywheel revolutions. Tests were performed at
      08:30 and 17:30 h, balanced for order with at least 72 hours between tests.
      Rectal temperature was lower pre-exercise in the morning (37.2 degrees C) than at
      evening (37.8 degrees C). This differences was reduced to 0.3 degrees C by the
      end of exercise. Mean power output was similar for the two times of day for the
      whole exercise period. A higher power output in the evening over the first half
      of the test was compensated for by a greater performance in the morning over the
      second 30 min (p < 0.05). It seems that the pacing of endurance performance is
      affected in the morning, but without any overall effect at least for the duration
      examined and at the ambient environmental temperature of 17-19 degrees C.

PMID- 7500636
TI  - Antibacterial activity of Helichrysum aureonitens (Asteraceae).
AB  - The antibacterial activity of extracts from Helichrysum aureonitens was
      investigated. The dichloromethane extract was active against all five gram
      positive bacteria tested and the methanol extract was active only against
      Bacillus cereus, B. pumilus and Micrococcus kristinae, while the water extract
      had no activity against any of the organisms. None of the extracts inhibited the
      growth of the five gram negative bacteria tested.

PMID- 7500635
TI  - Effects of Celastrus paniculatus on passive avoidance performance and biogenic
      amine turnover in albino rats.
AB  - The effects of an indigenous drug, Celastrus oil, extracted from the seeds of
      Celastrus paniculatus on learning and memory in a two compartment passive
      avoidance task was studied in albino rats. The effects on the contents of
      norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the brain and on the
      levels of their metabolites both in the brain and urine were also assessed.
      Significant improvement was observed in the retention ability of the drug treated
      rats compared with the saline administered controls. The contents of NE, DA and 5
      HT and their metabolites in the brain were significantly decreased in the drug
      treated group. The urinary metabolite levels were also significantly decreased
      except for total 3-methoxy-4-hydroxyphenyl glycol. These data indicate that
      Celastrus oil causes an overall decrease in the turnover of all the three central
      monoamines and implicate the involvement of these aminergic systems in the
      learning and memory process.

PMID- 7500637
TI  - The anti-oxidant activity of turmeric (Curcuma longa).
AB  - The turmeric anti-oxidant protein (TAP) had been isolated from the aqueous
      extract of turmeric. The anti-oxidant principle was found to be a heat stable
      protein. Trypsin treatment abolished the anti-oxidant activity. The anti-oxidant
      principle had an absorbance maximum at 280 nm. After gel filtration, the protein
      showed a 2-fold increase in anti-oxidant activity and showed 2 bands in the SDS
      PAGE with approximate molecular weight range of 24,000 Da. The protein showed a
      concentration-dependent inhibitory effect on the promoter induced lipid
      peroxidation. A 50% inhibitory activity of lipid peroxidation was observed at a
      protein concentration of 50 micrograms/ml. Ca(2+)-ATPase of rat brain homogenate
      was protected to nearly 50% of the initial activity from the lipid peroxidant
      induced inactivation by this protein. This protection of Ca(2+)-ATPase activity
      was found to be associated with the prevention of loss of -SH groups.

PMID- 7500638
TI  - Hepatoprotective activity of carrot (Daucus carota L.) against carbon
      tetrachloride intoxication in mouse liver.
AB  - The effect of carrot extract on carbon tetrachloride (CCl4)-induced acute liver
      damage was evaluated. The increased serum enzyme levels (viz., glutamate
      oxaloacetate transaminase, glutamate pyruvate transaminase, lactate
      dehydrogenase, alkaline phosphatase, sorbitol and glutamate dehydrogenase) by
      CCl4-induction were significantly lowered due to pretreatment with the extract.
      The extract also decreased the elevated serum bilirubin and urea content due to
      CCl4 administration. Increased activities of hepatic 5'-nucleotidase, acid
      phosphatase, acid ribonuclease and decreased levels of succinic dehydrogenase,
      glucose-6-phosphatase and cytochrome P-450 produced by CCl4 were reversed by the
      extract in a dose-responsive way. Results of this study revealed that carrot
      could afford a significant protective action in the alleviation of CCl4-induced
      hepatocellular injury.

PMID- 7500639
TI  - Ayurvedic herbal drugs with possible cytostatic activity.
AB  - Ayurveda is considered to be the traditional science of health in India and is
      based on the principle of subjectivity. All matter is composed of five basic
      elements, which can be perceived by the five sense organs. All food and drugs are
      classified according to their pharmacological properties, which are derived from
      these five elements. To investigate which Ayurvedic plants might have cytostatic
      activity, an Ayurvedic model for the pathogenesis of cancer was made. Based on
      this, selection criteria were formed, that were used to select plants from a list
      of Ayurvedic herbal drugs. Some of the selected species could be collected in
      India and Nepal. The dried material of 14 species was submitted to ethanol (70%
      v/v) extraction and the extracts were tested for cytotoxicity on COLO 320 tumour
      cells, using the microculture tetrazolium (MTT) assay. The IC50-value, the
      concentration causing 50% growth inhibition of the tumour cells, was used as a
      parameter for cytotoxicity. Extracts of the flowers of Calotropis procera (Ait.)
      R. Br. (Asclepiadaceae) and of the nuts of Semecarpus anacardium L.f.
      (Anacardiaceae) displayed the strongest cytotoxic effect with IC50-values of 1.4
      micrograms/ml and 1.6 micrograms/ml, respectively. The extracts of several other
      plants did not show a cytotoxic effect up to 100 micrograms/ml, the highest
      concentration tested.

PMID- 7500640
TI  - Anti-inflammatory activity of the bark of Hippocratea excelsa.
AB  - The ethanol extract of the plant Hippocratea excelsa was examined for its anti
      inflammatory effects using several animal models. It produced significant
      inhibition of carrageenan-induced paw edema and reduced the weight of cotton
      pellet-induced granuloma at doses of 25-100 mg/kg. The extract was found to exert
      a protective effect on heat-induced erythrocyte lysis at concentrations of 25, 50
      and 100 micrograms/ml. In chronic models of formaldehyde and adjuvant arthritis,
      its anti-arthritic activity was found to be less than that of phenylbutazone
      (PNB). It may be inferred that the ethanol extract is effective against both
      exudative-proliferative and chronic phases of inflammation.

PMID- 7500641
TI  - Cardioactive effects of Eremophila alternifolia extracts.
AB  - An aqueous extract obtained from the leaves of the traditional Aboriginal
      medicinal plant Eremophila alternifolia R.Br. (Myoporaceae) was tested on
      isolated hearts of normotensive rats using the Langendorff heart preparation. A
      single injection of the extract into the retrograge perfusion solution induced
      cardioactivity, consisting of a short initial increase in force of contraction
      (positive inotropism), followed by a decrease in the force (negative inotropism)
      with simultaneous increase in heart rate (positive chronotropism) and in coronary
      perfusion rate. These effects were not mediated by alpha- or beta-adrenergic
      receptors.

PMID- 7500642
TI  - Antibacterial activity and phytochemical analysis of Vochysia divergens
      (Vochysiaceae).
AB  - Vochysia divergens Pohl (Vochysiaceae) is a tree commonly found in wet soils of
      'Pantanal' of Mato Grosso, Brazil, and used in folk medicine against infections
      and asthma. We have studied different extracts and some isolated compounds from
      this plant for antibacterial activity. From the extracts of the stem bark beta
      sitosterol, betulinic acid and sericic acid were isolated. The minimal inhibitory
      concentration (MIC) for Staphylococcus aureus were: ethanolic extract (MIC = 1.5
      mg/ml); ethyl acetate extract (MIC = 2.0 mg/ml); and sericic acid (MIC = 1.0
      mg/ml). Escherichia coli was resistant until 5 mg/ml.

PMID- 7500643
TI  - Leukemia cell lines: in vitro models for the study of acute promyelocytic
      leukemia.
AB  - Acute promyelocytic leukemia (APL) serves as a paradigm in clinical and
      biological leukemia research. Firstly, APL represents a model for the new
      therapeutic approach of differentiation therapy, taking advantage of the ability
      of APL cells to respond to retinoic acid treatment by terminal differentiation.
      Secondly, the 15;17 chromosomal translocation specific for APL leads at the
      molecular genetic level to a chimeric gene fusing the PML and RAR alpha genes and
      appears to be an instrumental, if not actually the causative event, in the
      neoplastic process. These unique characteristics of an otherwise rather rare
      disease have recently attracted intense research interest. As in other types of
      leukemia where continuous cell lines are powerful research tools, studies using
      APL-derived cell lines have contributed a large body of relevant data in efforts
      to unravel the pathobiology and leukemogenesis of APL. Three cell lines have been
      reported to be derived from patients with APL: HL-60, NB-4 and PL-21. Both HL-60
      and PL-21 lack t(15;17) while NB-4 carries this cytogenetic hallmark
      pathognomonic for APL. Morphological and immunophenotypical examinations of the
      cell lines do not permit a clear assignment to any stage of myelomonocytic
      differentiation. Some additional data, such as expression of myeloperoxidase,
      monocyte-specific esterase and annexin VIII, together with the cytogenetic and
      molecular biological information, suggest that NB-4 is the only genuine
      promyelocytic leukemia cell line, whereas HL-60 may represent a discrete stage of
      differentiation between the late myeloblasts and the promyelocyte; PL-21 has
      distinct features associated with monocytic cells. These cell lines provide
      unique in vitro model systems for studying the cellular and molecular events
      involved in the proliferation and differentiation of normal and leukemic
      myelomonocytic cells.

PMID- 7500644
TI  - Distribution of cell cycle times amongst the leukemia cells within individual
      patients with acute myelogenous leukemia.
AB  - Seventeen patients with AML received infusions of BrdUrd to permit measurement of
      the cell parameters of leukemia cells in vivo. The range of S-phase times was
      measured by using a two color BrdUrd/Pl analysis to determine the range of BrdUrd
      incorporation into cells which had been in S-phase throughout the entire duration
      of BrdUrd administration. These data were, in turn, used to calculate the range
      of cell cycle times amongst the leukemia cells present within individual
      patients. The range of cell cycle times amongst the leukemia cells present within
      individual patients differs between patients, with some leukemia cell populations
      characterized by narrow and others by broad ranges. In general, the longer the
      mean cell cycle time (between 27 and 112 h) the broader the range of cell cycle
      times. These differences may help to explain, in part, the differences in
      response to therapy among patients whose mean leukemia cell kinetic parameters
      are similar.

PMID- 7500645
TI  - Differential expression of c-myc, max and mxi1 in human myeloid leukemia cells
      during retrodifferentiation and cell death.
AB  - Previous studies in human myeloid leukemia cells (HL-60, U-937, THP-1) suggested
      an involvement of the c-myc gene in the control of mutually exclusive pathways,
      such as retrodifferentiation and cell death. Treatment of U-937 cells with 12-O
      tetradecanoyl phorbol-13-acetate (TPA) which is associated with the induction of
      a monocytic differentiation program and growth arrest, revealed an initial up
      regulation of c-myc, c-max, and mxi1 mRNAs after 1-6 h. Thereafter expression of
      these genes significantly declined to barely detectable levels when the cells
      ceased to grow after 12-24 h of TPA treatment. Between 7 and 11 days of TPA
      induced G0/G1 cell cycle arrest, expression of the c-max and mxi1 genes
      continuously increased up to 8-fold until 32 days and declined to control levels
      when the cells regained proliferative capacity by 36 days. In contrast, c-myc
      mRNAs remained down-regulated during periods of growth arrest and increased only
      during re-entry into the cell cycle after 36 days. This effect is consistent with
      a retrodifferentiation process, whereby previously differentiated cells revert
      back to the undifferentiated phenotype and re-enter the cell cycle. Different
      results were obtained during serum starvation-induced cell death of U-937 cells.
      After 48-72 h of serum-starvation, expression of the c-myc and c-max genes were
      significantly down-regulated by 4-fold and 3-fold, respectively, while there was
      little, if any, change in mxi1 mRNA levels. Analysis of cell death in serum
      starved U-937 cells demonstrated progressively increasing DNA fragmentation
      reaching 45.4% +/- 0.9% after 72 h. Synchronization of proliferating U-937 cells
      throughout distinct phases of the cell cycle exhibited little, if any, change in
      c-myc, c-max and mxi1 mRNAs. Furthermore, like c-myc, c-max and mxi1 mRNA
      transcripts appeared to be regulated primarily by post-transcriptional
      mechanisms, and c-max and mxi1 half-lives exceeded 4 h in contrast to < 60 min
      for the c-myc gene. Taken together, these findings suggested differential
      regulation and inverse expression levels of c-myc compared to c-max and mxi1
      during differentiation, retrodifferentiation and cell death.

PMID- 7500646
TI  - Somatostatin and its cyclic octapeptide analog SMS 201-995 as inhibitors of
      proliferation of human acute lymphoblastic and acute myeloid leukemia.
AB  - Somatostatin (SS) is a 14 amino acid peptide which is secreted by the
      hypothalamus and the pancreatic islets. It expresses antiproliferative activity
      in various organ systems, experiments have suggested effects of SS on
      hematopoietic cells. Here we present investigations regarding the effect of SS
      and its analog SMS 201-995 (SMS) on the in vitro proliferation of acute
      lymphoblastic leukemia (ALL; n = 7 cases), acute myeloid leukemia (AML; n = 21
      cases) and chronic lymphocytic leukemia (CLL; n = 2 cases). Both SS and SMS
      inhibited spontaneous leukemic cell growth in approximately 1/3 of cases (i.e.
      7/19). G-CSF stimulated AML cells were inhibited by SMS in 11/21 cases. AML cell
      proliferation induced by IL-3 or GM-CSF was suppressed in only 3/21 and 6/21
      cases, respectively. In ALL cells, IL-7-induced proliferation was suppressed by
      SMS in 3/7 cases. The effect of SMS seemed to depend on the type of the
      hematopoietic growth factor, and on their concentrations. In fact, high
      concentrations of G-CSF could override SMS blocking completely. Colony formation
      by normal marrow progenitors and DNA synthesis by HL-60 and T11/65 leukemic cell
      lines were not affected by SMS. In conclusion, somatostatin may act as a negative
      regulator of the proliferative activity of human leukemia.

PMID- 7500647
TI  - Modulation of HSP70 and HSP27 gene expression by the differentiation inducer
      sodium butyrate in U-937 human promonocytic leukemia cells.
AB  - The treatment of U-937 human promonocytic cells with the differentiation inducer
      sodium butyrate (0.75 mM) transiently increased heat-shock protein 70 (HSP70)
      mRNA levels between 3 and 6 h, and heat-shock protein 27 (HSP27) mRNA levels
      between 12 and 24 h, as indicated by northern blot assays. Gel retardation assays
      indicated that butyrate also stimulated heat-shock factor (HSF) binding activity
      between 3 and 6 h, suggesting that the activation of HSP70 gene expression was
      mediated by the heat-shock factor DNA response element (HSE). In addition, the
      treatment provoked a biphasic alteration of the c-fos mRNA level, consisting of a
      slight increase between 0.5 and 3 h followed by a greater increase between 12 and
      48 h, while it caused a single increase between 12 and 48 h in c-jun mRNA level.
      The possible involvement of the heat-shock protein genes in the butyrate-induced
      differentiation of U-937 cells is discussed.

PMID- 7500648
TI  - Abnormal regional hypermethylation of the calcitonin gene in myelodysplastic
      syndromes.
AB  - Abnormal regional hypermethylation of the calcitonin gene can be detected in up
      to 95% of patients with acute nonlymphocytic leukemia (ANLL). We used a
      polymerase chain reaction (PCR) based assay to detect abnormal regional
      hypermethylation at this locus in patients with primary myelodysplastic syndromes
      (MDS). Hypermethylation was detected in 13 of 20 patients (65%) with MDS and was
      detected in nine patients with MDS and normal cytogenetics. There was no
      correlation between detection of this abnormality and the subtype of MDS. Four of
      the 13 patients (30%) with abnormal methylation have progressed to ANLL with a
      median time to progression of 3.5 months. The actuarial median survival of the
      cohort with abnormal methylation was 17 months, while that of the cohort with
      normal methylation is not yet reached. These preliminary findings suggest that
      detection of abnormal methylation at this locus may be useful as a diagnostic
      tool in MDS. Furthermore, hypermethylation of the calcitonin gene may be a poor
      prognostic feature that predicts progression to acute leukemia in patients with
      primary MDS.

PMID- 7500649
TI  - Elevated levels of p53 protein in the neutrophils and monocytes of a patient with
      chronic idiopathic thrombocytopenic purpura or possible early myelodysplasia?
AB  - A 68 year old female who presented with long-term thrombocytopenia was clinically
      diagnosed as having chronic idiopathic thrombocytopenia purpura (ITP). Increased
      levels of the tumour suppressor p53 protein were detected by immunohistochemistry
      in the neutrophils and some monocytes of the peripheral blood preparation using
      the antibody DO-1, recognizing mutant and wild type p53 protein conformations.
      However, no positive staining in the peripheral blood samples from 41
      myelodysplasias (MDS) and six normal individuals was observed. Single-stranded
      conformational polymorphism analysis performed on DNA extracted from the cytospin
      preparations from this patient indicated no mutations in exons 5-8 of the p53
      gene. This report describes the unusual detection of elevated p53 protein in a
      non-neoplastic condition by immunohistochemistry using the antibody DO-1. This
      unexpected finding raises the possibility of classifying such patients as early
      MDS on the basis of their p53 status.

PMID- 7500651
TI  - Constitutional and acquired trisomy 8.
AB  - Trisomy 8 is seen in a range of disorders both constitutional and acquired. The
      full constitutional condition presents with physical stigmata, skeletal
      abnormalities and a mild to moderately retarded IQ. Trisomy 8 is frequently seen
      as a mosaic in the blood or in the skin or both. Trisomy 8 as an acquired
      condition is found in haematological disorders, notably in myelodysplasia (MDS)
      and acute myeloid leukaemia (AML), and is restricted to the malignant cells.
      These arise in the bone marrow and may also be found in the peripheral blood.
      Reported in the issue (Zollino et al. (1995) Leukemia Res. 19(10), 733) is a case
      of a patient with constitutional trisomy 8 mosaicism who developed myelodysplasia
      with trisomy 8 in 95-100% of bone marrow cells. Here we consider the implications
      of this case to the diagnosis of both malignant and constitutional conditions.

PMID- 7500650
TI  - Constitutional trisomy 8 and myelodysplasia: report of a case and review of the
      literature.
AB  - A diagnosis of myelodysplastic syndrome was made in an 18-year-old patient with
      Warkany syndrome due to constitutional trisomy 8 mosaicism. The possible causal
      role of this particular chromosome constitution with respect to myelodysplasia
      and embryonal childhood tumors is discussed.

PMID- 7500652
TI  - Possible co-existence of RAS activation and monosomy 7 in the leukaemic
      transformation of myelodysplastic syndromes.
AB  - The frequency of RAS activation was studied in 48 patients with acute myeloid
      leukaemia (AML) or with myelodysplastic syndromes (MDS), in order to address the
      question of whether patients possessing monosomy 7 or other alterations of
      chromosome 7 have a higher incidence of RAS activation than those lacking
      chromosome 7 abnormalities. Samples were screened for oncogenic point mutation by
      DNA amplification followed by oligonucleotide hybridization analysis at codons
      12, 13 and 61 of N-RAS and codons 12 and 13 of K-RAS. Two additional samples were
      considered to have activated RAS due to additional karyotypic abnormalities
      t(5;12) or loss of both copies of chromosome 17 and hence, the neurofibromatosis
      (NF1) loci. The group of chronic myelomonocytic leukaemia (CMML) patients had
      activated RAS in 4/11 cases and inclusion of two CMMLt patients (with monosomy 7)
      brings this incidence to 5/13. No change in frequency of RAS activation was seen
      between groups containing de novo AML samples with or without chromosome 7
      abnormalities (1/5 and 2/12, respectively). However, assessment of MDS samples in
      the process of, or subsequent to, leukaemic progression showed a difference
      between the two groups. The frequency of RAS activation in samples with monosomy
      7 was 4/9 samples while none of the seven samples without chromosome 7 changes
      showed RAS activation. The co-existence of RAS activation and monosomy 7 in MDS
      indicates that these lesions can co-operate in the multistep process of
      leukemogenesis.

PMID- 7500653
TI  - Erythroid differentiation and growth inhibition of K562 cells by 2',5'
      dideoxyadenosine: synergism with interferon-alpha.
AB  - We found that 2',5'-dideoxyadenosine (DDA), a P-site specific adenylate cyclase
      inhibitor, inhibited the growth of K562 cells and caused them to become benzidine
      positive. The continuous exposure of cells to DDA was needed to recruit cells for
      growth inhibition and differentiation. Fetal calf or human sera were also
      necessary for DDA to induce differentiation. DDA at a concentration of 1.5 mM
      with serum induced 98% of the cells to produce hemoglobin and inhibited their
      growth to 15% of that of the control. An increase of epsilon-globin mRNA and a
      decrease of c-myc and c-myb mRNA occurred only during differentiation in the
      presence of fetal calf serum (FCS). An incubation with DDA and interferon-alpha
      (IFN-alpha) or hemin synergistically induced more benzidine-positive cells than
      in the presence of DDA alone, although IFN-alpha did not trigger differentiation
      by itself. The erythroid differentiation and growth inhibition were, however, not
      related to a decreased intracellular cyclic AMP (cAMP) concentration induced by
      DDA. The simultaneous incubation with dibutyryl cyclic AMP (dbc-AMP) and DDA
      enhanced the effects of DDA. Adenine, a possible metabolite of DDA digestion by
      purine nucleoside phosphorylase (PNP), also induced erythroid differentiation in
      K562 cells. However, it did not act synergistically with IFN-alpha.

PMID- 7500654
TI  - Pharmacokinetics of mitoxantrone, etoposide and cytosine arabinoside in leukemic
      cells during treatment of acute myelogenous leukemia--relationship to treatment
      outcome and bone marrow toxicity.
AB  - Twenty-seven patients with acute myelogenous leukemia (AML) were given remission
      induction treatment with mitoxantrone, etoposide and cytosine arabinoside (ara
      C). The pharmacokinetics in leukemic blood cells of mitoxantrone, etoposide and
      the active metabolite of ara-C, ara-CTP, were determined during the first day of
      treatment. There was a large interpatient variability of the area under the time
      versus concentration curve (AUC) for all three drugs. On the individual level,
      there was no correlation between the AUCs of the different drugs. Neither did the
      AUC of any individual drug nor the calculated total intracellular drug exposure
      have any association with the outcome of treatment or hematological toxicity,
      measured as duration of leukopenia/thrombocytopenia. In conclusion, when
      combination chemotherapy with mitoxantrone, etoposide and ara-C is given to
      patients with AML, intracellular drug concentrations, achieved after the first
      dose of each drug, do not seem to be predictive for treatment response or
      hematological toxicity.

PMID- 7500655
TI  - A dose intensive regimen of cytosine arabinoside and daunorubicin for chronic
      myelogenous leukemia in blast crisis.
AB  - Fourteen consecutive patients with chronic myelogenous leukemia (CML) blast
      crisis were treated with a more dose-intensive regimen of daunorubicin (70 mg/m2
      per day on days 1-3) and cytosine arabinoside (200 mg/m2 per day as continuous
      infusion on days 1-9) than usually used in de novo acute myelogenous leukemia.
      The median age of the patients was 50 years (27-78 years). Eleven of 13 evaluable
      patients were aplastic at day 14 after a single course of therapy (11/13, 85%).
      Over-all response rate (complete + partial response) was 9/13 (69%). Restoration
      to chronic phase was achieved in 7/13 patients (54%) lasting a median of 78 days
      (49-235 days). However, four of these seven patients proceeded to bone marrow
      transplant (BMT) and so the true remission duration for this therapy cannot be
      determined. Treatment-related mortality was 4/14 (29%). Presently, four of nine
      patients evaluable are surviving post-induction, three S/P allogeneic BMT (0.6,
      3.8, 5 years) and one patient S/P autologous BMT (3.3 years post-induction).
      These results of an intensive induction regimen achieving marrow aplasia in all
      except one patient to date warrants further study as the first step possibly
      towards BMT after CML blast crisis.

PMID- 7500656
TI  - Calla positive acute lymphoblastic leukemia after etoposide-based therapy for
      Ewing's sarcoma.
AB  - This is an unusual and interesting case report concerning a 10 year old boy with
      an initial diagnosis of Ewing's sarcoma of the right tibia. He was successfully
      treated with a chemotherapy regimen consisting of vincristine, cyclophosphamide
      (cumulative dose 7200 mg/m2), doxorubicin, etoposide (cumulative dose 2700 mg/m2)
      and cisplatin and local radiotherapy to the tibia. After an interval of 37 months
      he developed CALLA positive acute lymphoblastic leukemia with 11q23 chromosomal
      abnormality. The possible roles of etoposide and cyclophosphamide are discussed.

PMID- 7500657
TI  - Adverse selection among multiple competing health maintenance organizations.
AB  - This study examines risk selection among nine health plans competing for 16,182
      employees of one large firm in 1989: one conventional fee-for-service plan, one
      group-model health maintenance organization (HMO), and seven network and
      independent practice model HMOs. We develop and compare measures of risk using
      weights based on HMO and fee-for-service expenditure data, respectively. We use a
      multiequation statistical model to develop two sets of utilization and
      expenditure weights for enrollees in each plan. One set of weights, based on
      discharge abstracts and outpatient records from the large group-model HMO,
      measures how much each of the nine groups of employees and dependents would have
      spent, had they been enrolled in a stringently managed plan with no consumer cost
      sharing. The other set of weights, based on fee-for-service claims data, measures
      how much each group would have spent, had it been enrolled in an unmanaged health
      plan with significant coinsurance and deductibles. Predicted annual expenditures
      per enrollee exhibit a 23% range from lowest (favorable selection) to highest
      (adverse selection) risk plans using the HMO weights and a 17% range using fee
      for-service weights. The fee-for-service plan and group-model HMO with large
      enrollments have risk mixes near the center of the spectrum. Smaller HMOs exhibit
      the extreme forms of both favorable and adverse selection. The statistical
      methods adopted in this study can be used to risk-adjust capitation payments to
      competing health plans. As mergers among HMOs and group purchasing arrangements
      among employers increase the average enrollment in each plan from each payor,
      however, risk differences among plans will be attenuated and the need to risk
      adjust payments will be less severe. Key words: health insurance; adverse
      selection; managed competition; health maintenance organization.

PMID- 7500658
TI  - Patient and visit characteristics related to physicians' participatory decision
      making style. Results from the Medical Outcomes Study.
AB  - This article identifies the characteristics of patients and office visits
      associated with decreased mutual decision-making between physicians and patients.
      In the baseline cross-sectional survey of the Medical Outcomes Study we measured
      specific patient characteristics hypothesized to influence participatory decision
      making (PDM) styles of physicians. We related these characteristics to the PDM
      style scores for their physicians. The study was conducted in solo practices,
      multi-specialty groups, and health maintenance organizations in Boston, Chicago,
      and Los Angeles. Over a 9-day period in 1986, 8,316 patients were sampled from
      the practices of 344 participating Medical Outcome Study physicians, representing
      general internal medicine, family practice, cardiology and endocrinology.
      Physicians' PDM style was measured using a 3-item scale included on the baseline
      questionnaire completed by patients after office visits to their Medical Outcome
      Study physicians. We found that the elderly (age 75 and older) and young adult
      (younger than age 30) patients, patients with high school education or less,
      minority patients, and male patients had the least participatory visits with
      their physicians. We also found that male patients seeing male physicians had the
      least participatory visits compared with male patients seeing female physicians,
      and compared with female patients seeing physicians of either gender. Our data
      indicated that PDM style increased as duration or tenure of the physician-patient
      relationship increased. Participatory decision-making style also increased with
      increasing length of office visits. The role of effective interpersonal care in
      optimizing patients' health outcomes may be underappreciated. We have identified
      seven patient and visit characteristics that maximize or compromise the
      effectiveness of interpersonal care. Recognizing those at risk for suboptimal
      interpersonal care may be a first step in improving the management of chronic
      disease. Key words: participatory decision-making style; interpersonal care;
      doctor-patient communication.

PMID- 7500659
TI  - Expected hospital costs of knee replacement for rural residents by location of
      service.
AB  - This article assesses the relative cost of providing a specific procedure, knee
      replacement (KR) surgery, to rural residents in rural community-based hospitals
      rather than in urban hospitals. Costs are predicted using regression analysis
      with readily available data from Health Care Financing Administration's Medicare
      Provider Analysis and Review. The specification incorporates the effect of
      referral patterns on volume and the subsequent impact on costs in the different
      settings. The predicted cost per case was found to be lower in rural rather than
      urban hospitals across all patient types. Findings indicate scale economies exist
      for KR surgery in both the urban and rural hospital settings. Results also
      suggest the total cost of a hospitalization associated with KR surgery in rural
      hospitals is more sensitive to changes in procedure volume than in urban
      hospitals, providing preliminary support for increased regionalization of KR
      surgery in rural hospitals. While long-term outcome measures associated with
      successful KR surgery (improved function, reduced pain, etc.,) are not available,
      mortality rates and perisurgical complication rates were not significantly
      different between rural patients who received KR surgery in rural hospitals and
      those who received KR surgery in urban hospitals. Among rural hospitals, however,
      complication rates were significantly correlated with procedure volume
      (complication rates were significantly lower in rural hospitals that performed
      more than nine KR surgeries a year). Our results suggest KR surgery can be
      delivered efficiently in rural community-based settings and support the case for
      regionalization of this procedure. Key words: rural hospital; hospital cost;
      economics of scale; regionalization.

PMID- 7500660
TI  - Evaluating long-term care demonstrations in real time with study design and plan
      performance interactions.
AB  - The evaluation of long-term care demonstrations has to deal with complex
      organizational entities, with large, heterogeneous client populations that,
      during the course of study, may have to change features of their organization or
      operation. The implications of such "real-time" changes are discussed for
      analyses of the operation and performance of Social/Health Maintenance
      Organizations over a 5-year period (2 years of start-up and enrollment and 3
      years of follow-up). Analyses conducted of the plans in the context of real-time
      changes have to be based on different statistical models than for classic
      experimental study designs, where treatment factors are fixed rather than
      dynamic. A number of issues that may arise are identified, and possible
      approaches to their solutions described. Key words: long-term care;
      demonstrations; evaluations; study design; capitation.

PMID- 7500662
TI  - Health and health care. Experience with a population-based health information
      system.

PMID- 7500661
TI  - A method for adjusting capitation payments to managed care plans using
      multivariate patterns of health and functioning: the experience of Social/Health
      Maintenance Organizations.

PMID- 7500663
TI  - Stability and trends over 3 years of data.
AB  - Because the health status of a population does not usually respond immediately to
      interventions, whether social or medical, the ability to analyze change over time
      is important. Therefore, patterns of change and stability in health status and
      health care use of Manitoba residents during a 3-year period from 1990 to 1992
      were analyzed using the Population-based Health Information System. This article
      presents summary findings and discusses methodological and policy issues arising
      from the analyses. A small but significant decrease in premature mortality (the
      primary health status indicator) was observed in most regions of the province,
      but two remote, northern regions, those whose residents scored at high
      socioeconomic risk, remained distinguished for their poor health status. These
      "poor health" regions also had the highest contact rates with primary caregivers,
      raising questions about the role of the health care system in improving the
      health of the population. A persistent increase in surgery was observed in
      several regions, led by increases in outpatient surgery over and above increases
      in the elderly population and beyond substitution for inpatient procedures. This
      trend (not obvious before these analyses) is important as hospitals move to
      expand their outpatient facilities in response to restraints on inpatient care.

PMID- 7500664
TI  - Using the information system to assess change: the impact of downsizing the acute
      sector.
AB  - A population-based approach was used to monitor impact of hospital bed closures
      in Winnipeg, Manitoba. Four years of administrative data were analyzed. Access to
      hospital services was not adversely affected: The reduction in beds resulted in
      increases in outpatient surgery and earlier discharges. In addition, access
      favored the admission of persons with more health care needs. Quality of care, as
      measured by mortality within 3 months of admission, readmission rates within 30
      days of discharge, and increased contact with physicians within 30 days of
      discharge, did not change. The health status of the Winnipeg population, measured
      by premature mortality, did not change. However, health status and hospital use
      was found to be strongly related to socioeconomic status. In light of this
      gradient, the authors conclude that well designed and evaluated experiments that
      focus on the determinants of health, rather than on providing more health care
      services, could help identify ways of reducing hospital use.

PMID- 7500665
TI  - The Population Health Information System: data analysis and software.
AB  - This article describes the software developed in the process of creating the
      Population Health Information System. The software can be applied to a range of
      administrative data and provides standardized data on the health status and
      health care use of populations by generating population-based rates of discrete
      events. The standardized approach permits construction of a comprehensive,
      comparative picture for residents of defined geographic regions. The addition of
      a user friendly graphic interface will permit regional planners to do their own
      data analyses and allow out-of-province researchers to adopt the system for their
      own uses.

PMID- 7500667
TI  - From research to policy: what have we learned from designing the Population
      Health Information System?
AB  - This article discusses the lessons learned from the experience of designing and
      using a population health information system and the policy implications of
      information generated. A useful system must include measures of the population's
      health status and socioeconomic risk when analyzing health care use. The strong
      gradient that can be demonstrated in service use across income groups where these
      indicators are included challenges policymakers and health care managers to
      rethink fundamental beliefs about the role of medical care. Given the size of
      health care expenditures in western economies, the author argues for redirecting
      some of these resources toward other means of improving the health of
      populations. Outcomes research should be expanded to assess the efficacy of non
      medical and medical interventions. A population-based health information system
      can help identify opportunities for shifting expenditures toward meliorating the
      determinants of health, while monitoring the health care system to ensure that
      adverse effects do not occur.

PMID- 7500666
TI  - A population-based health information system.
AB  - The authors introduce the Population Health Information System, its conceptual
      framework, and the data elements required to implement such a system in other
      jurisdictions. Among other innovations, the Population Health Information System
      distinguishes between indicators of health status (outcomes measures) and
      indicators of need for health care (socioeconomic measures of risk for poor
      health). The system also can be used to perform needs-based planning and
      challenge delivery patterns.

PMID- 7500668
TI  - Measuring the health of the population.
AB  - A set of 102 population-based indicators was developed from multiple
      administrative data sources; these indicators were used to compare the health
      status of 1 million Manitoba residents across eight administrative regions for 1
      year. Marked variations in health status were shown. Despite theoretically equal
      access to care in a universally insured system and high rates of utilization of
      hospital and physician services, residents of Manitoba's two northern, more
      remote regions scored most poorly--consistently and with statistical significance
      -across a variety of health status indicators. The strength of the various
      indicators was evaluated, and premature mortality emerged as the most useful
      "flagship" indicator for future analyses. Indicators that purport to be sensitive
      to how well a health care system is performing showed patterns similar to those
      derived from more classic measures (eg, mortality, low birth weight).
      Furthermore, the "system sensitive indicators" did not appear to be sufficiently
      independent of utilization biases.

PMID- 7500669
TI  - Socioeconomic status and the health of the population.
AB  - To examine the relationship of a population's socioeconomic characteristics to
      its health status and use of health care services, a composite socioeconomic risk
      index was developed for the Population Health Information System. From a set of
      23 socioeconomic indicators derived from public use census data, a summary index
      was formed from six indicators to generate profiles for the eight health regions
      of the province. Regional scores were plotted against an index of health status
      measures and against measures of health care utilization. Strong regional
      variations were found in all of these measures, and the socioeconomic risk index
      explained 87% to 92% of the differences in health status and acute
      hospitalizations. Moreover, regions with the worst health status on our
      indicators were found to be among the highest consumers of health services. The
      socioeconomic risk index appears to be a powerful tool in clarifying which
      benefits in improved health status might accrue from changing the underlying
      inequities in amenable socioeconomic risk factors, rather than simply increasing
      services to regions of low health status.

PMID- 7500670
TI  - Utilization of hospital resources.
AB  - A population-based approach was used to analyze the utilization patterns of
      hospital care by Manitoba residents during the fiscal year 1991/1992. Patterns
      were analyzed for eight administrative regions, with use assigned to the
      patient's region of residence, regardless of the location of the hospitalization.
      Regional boundaries consistent with those used for presentation of data on health
      status and socioeconomic risk permitted integration of findings across the
      Population Health Information System. Marked differences in acute hospital use
      were found. Residents of the urban Winnipeg ("good health") region had the lowest
      rates of use of acute care overall, and northern rural ("poor health") regions
      had significantly higher rates of use. However, almost one half of hospital days
      by Winnipeg residents were used in long-stay care (60+ days), while rural
      residents were more likely to use short-stay hospital care. Despite a
      concentration of surgical specialists in Winnipeg, there were only small regional
      differences in overall rates of surgery.

PMID- 7500671
TI  - A productive experiment with administrative data.

PMID- 7500673
TI  - Utilization of physician resources for ambulatory care.
AB  - This article describes the utilization of ambulatory physician services by
      Manitoba residents during the fiscal year 1991/1992. Care was assigned to the
      patient's residence in one of eight administrative regions, whether the care was
      received in or out of the region of residence. Disparities in physician supply
      across regions did not correspond with differences in the use of services: the
      Winnipeg region had twice as many physicians per 1000 residents as the largely
      rural non-Winnipeg regions and was home to most specialists. With their rich
      supply of physicians, particularly specialists, Winnipeg residents had somewhat
      higher contact rates (16%), and the province spent 26% more per resident
      providing physician services, despite the fact that our indicators of health
      status and socioeconomic risk suggest no increased need for physician services
      among Winnipeg residents. Despite the concentration of physicians in Winnipeg,
      there was remarkably good access to physicians across the province, with 78% or
      more of the residents in every region making at least one contact with a
      physician during the year. The differences in use between Winnipeg and non
      Winnipeg residents were almost entirely accounted for by intensive users,
      (individuals making eight or more visits per year). Although residents 75 years
      of age and older (6% of the population) made twice as many visits per capita
      compared to younger adults, their actual demand on the system was small,
      accounting for just less than 10% of expenditures on physician services.
      Population-based health information provides important insight for needs-based
      planning of physician services.

PMID- 7500672
TI  - Utilization of nursing home resources.
AB  - The total use and cost of nursing homes in Manitoba, for the fiscal year
      1991/1992 were analyzed using a population-based health information system. The
      use of hospital beds by elderly patients for stays of 60 days or more was also
      analyzed to see if long hospital stays were substituting for nursing home beds.
      More than one in ten Manitobans 75 years of age and older and one in three who
      were 85 years and older resided in a nursing home for some time during the study
      period. The nursing home sector is characterized by none of the marked
      differences previously found in hospital use across the southern regions of the
      province, whose residents are similar in health and need characteristics. A
      single entry system, combined with a population-based planning approach, appears
      to provide equitable access to care across the province.

PMID- 7500674
TI  - [Is measurement of basal levels of serum pepsinogen II useful in proving the
      eradication of Helicobacter pylori by treatment?].
AB  - BACKGROUND: The aim of this study was to demonstrate the influence of the
      eradication of Helicobacter pylori on the basal concentrations of serum
      pepsinogen II in patients with duodenal ulcer. METHODS: Thirty-two patients with
      active duodenal ulcer were prospectively studied. A triple therapy was used
      consisting in bismuth, metronidazole and tetracycline. At the time of initial
      endoscopy and in those performed 5 months later on completion of the treatment,
      biopsies of the gastric mucosa were taken for histologic and microbiologic
      studies, and the basal concentrations of serum pepsinogen II are also determined.
      RESULTS: The eradication of H. pylori was accompanied by a significant pathologic
      improvement (p < 0.001) in both the antrum and the gastric body. On eradication
      of H. pylori, the basal pepsinogen II value (m +/- SD) decreased from 9.2 +/- 2.7
      ng/ml to 6.4 +/- 1.7 ng/ml after treatment (p < 0.001). However, when eradication
      was not achieved, these values increased (11.8 ng/ml) with respect to the initial
      determination (9.3 ng/ml) (p < 0.05). The area under the ROC curve was 0.99 (SE
      0.01) with a sensitivity of 92% and specificity of 100% with respect to the
      diagnosis of infection eradication (cut off point of the decrease of pepsinogen
      levels O). CONCLUSIONS: The eradication of Helicobacter pylori in patients with
      duodenal ulcer is associated with a significant decrease in the basal
      concentrations of serum pepsinogen II measured 5 months after completion of
      treatment. The verification of this decrease constitutes a useful, inexpensive
      non invasive method to prove the eradication of H. pylori with treatment.

PMID- 7500675
TI  - [The importance of obtaining biopsies of the gastric body in the follow-up after
      eradicating treatment of Helicobacter pylori].
AB  - BACKGROUND: The aim of the present was to study the usefulness of performing
      biopsies of the gastric body in addition to those normally obtained of the antrum
      in the control of the eradication of Helicobacter pylori after treatment.
      METHODS: Sixty-four patients with duodenal ulcer and infection by H. pylori were
      prospectively studied. Two therapeutic schedules were used:
      amoxycillin/clavulanic associated with omeprazole (n = 32) and the classical
      triple therapy (bismuth, metronidazole, tetracycline) (n = 32). At the time of
      initial endoscopy and one month after completion of the treatment biopsies of the
      antrum and gastric body were taken for histologic (hematoxylin-eosin) and
      microbiologic (Gram and culture) studies. A patient was considered to have H.
      pylori infection when its presence was demonstrated by histologic or
      microbiologic methods in either of the localizations. RESULTS: The eradication of
      H. pylori was globally achieved in 64% (n = 41) of the cases. In the patients in
      whom eradication was not achieved (n = 23), H. pylori was detected only in the
      antrum in 70% (30% false negatives) while this was seen in the gastric body in
      96% of the cases (p < 0.05). CONCLUSIONS: Carrying-out biopsies of only the
      antrum after eradicating H. pylori treatment is associated with a high percentage
      of false negative diagnosis of infection. Therefore, additional biopsies of the
      gastric body are recommended.

PMID- 7500676
TI  - [Informatics in medical schools and postgraduate education centers for health
      professionals. Survey on the situation in Spain].
AB  - BACKGROUND: Informatics is acquiring an increasing relevance in the medical
      profession. METHODS: During the year 1993, a survey was carried out at the
      medical schools (MS) and postgraduate education centres (PEC) in Epidemiology,
      Public Health and Health Administration of Spain, on the available computer
      infrastructure and the teaching activities. The percentages of respondents were
      81 at the MS and 100 at the PEC. RESULTS: 81% of the MS and 100% of the PEC had a
      computer laboratory, mainly equipped with personal computers with MS-DOS
      operating system. The use of general purpose applications was predominant. The
      number of students using the computer laboratory was very variable (5-300 per
      day). 48% of the MS organized courses on microcomputer applications. 66% of the
      MS included subjects related with informatics in the new curricula. CONCLUSIONS:
      Use of computers in the Spanish MS is heterogeneous. Compared with the Nord
      American MS, they do not usually use applications of computer-assisted
      instruction. The use of the computers at the PEC is much more generalized.

PMID- 7500677
TI  - [Helicobacter pylori: an etiologic factor in chronic gastritis, gastroduodenal
      ulcer and gastric cancer].

PMID- 7500678
TI  - [Ethics committees and clinical trials: it's more than change of name].

PMID- 7500679
TI  - [Historical framework for a new discipline: bioethics].

PMID- 7500681
TI  - [Pneumothorax and pneumomediastinum after bronchoalveolar lavage: can be
      avoided?].

PMID- 7500680
TI  - [Intraparenchymatous hematoma simulating transitory ischemia].

PMID- 7500682
TI  - [Pollakiuria and micturition syndrome related to fluoxetine].

PMID- 7500683
TI  - [Biopotency of tuberculins used in Spain].

PMID- 7500684
TI  - [Prevalence of cardiovascular risk factors in a working population].
AB  - BACKGROUND: A high prevalence of cardiovascular risk factors (RF) has been
      reported in Spain. The aim of this study was to determine the main RF of heart
      disease (cholesterol, smoking, high blood pressure (HBP), diabetes, obesity, and
      sedentarism) in laboral population from Granada, Spain. METHODS: The sample
      included 1,555 workers (1,193 males and 362 females, mean age 42.3 years). The
      percentage of participation was 91.9%. Information was collected directly
      (standardized self administered questionnaire) and from the physicians of the
      companies (protocolized anamnesis, physical examination and electrocardiogram)
      for each worker. Serum cholesterol was measured in venous blood by an enzymatic
      autoanalyzer. A description of the phenomennon was studied and likewise, the
      multivariate models of logistic regression were adjusted to evaluate the
      association of the other RF with hypercholesterolemia. RESULTS: Serum cholesterol
      level higher than 200 mg/dl (5.17 mmol/l) was presented in 69.3% of the sample.
      The prevalence of HBP was 8.4%. Forty-four point two percent were smokers (48.9%
      males and 28.7% females). A body mass index higher than 25 kg/m2 was presented in
      65.2%. The prevalence of diabetes was 3.5% and 18% of the workers classified
      themselves as sedentary. Only 2.8% of the males and 11.6% of the females were
      absolutely free of the RF studied. Diabetes, age, obesity, HBP and smoking (> 10
      cigarettes/day) were significantly associated with a higher probability to
      present hypercholesterolemia. CONCLUSIONS: A high prevalence of classical risk
      factors related to cardiovascular disease, with the exception of high blood
      pressure, was observed, thus making the application of preventive measures
      necessary.

PMID- 7500685
TI  - [Cost-effectiveness of pharmacologic treatments for the reduction of blood
      lipids].
AB  - BACKGROUND: The cost-effectiveness of hypolipemiant treatment with lovastatine
      (0.02, 0.04 and 0.08 g/day), cholestyramine (12 and 24 g/day), cholestipol (10
      and 20 g/day) and gemfibrocyl (1.2 g/day) was estimated in individuals presenting
      hypercholesterolemia (> 200 mg/dl or 5.17 mmol/l) following dietetic treatment.
      METHODS: The cost-effectiveness relationship was measured in terms of cost per
      year of life gained comparing the net cost of the program with its effectiveness
      for each treatment studied. The net cost of the program was calculated taking the
      costs associated with hypolipemiant treatment into account and subtracting the
      estimated reduction of the costs of coronary heart disease attributed to the
      prevention program. The Framingham equation and the information concerning to the
      prevalence of cardiovascular risk factors and life expectancy according to age
      and sex in the Catalonian (Spain) population were used to estimate the
      effectiveness. RESULTS: The lesser to greater cost per year of life gained is
      lovastatine-0.02, cholestyramine-12, cholestipol-12, lovastatine-0.04,
      gemfibrocyl, cholestyramine-24, cholestipol-10, lovastatine-0.08 and cholestipol
      20. In males from 45-49 years of age with cholesterol concentration of 300 mg/dl
      (7.76 mmol/l) the costs per year of life gained were 3.4 millions for lovastatine
      0.02, 4.6 for cholestyramine-12, 4.8 for lovastatine-0.04, 5.4 for gemfibrocyl,
      6.5 for cholestyramine-24, 7.8 for cholestipol-10, 8.1 for lovastatine 0.08 and
      11.6 for cholestipol-20. In women the cost-effectiveness were 11.6, 15.4, 17.7,
      21.3, 25.4, 25.9 and 37.1, respectively. The cost-effectiveness for the most
      effective treatments was less than 5 million of pesetas per year of life gained
      in males presenting a cholesterol concentration higher than 300 mg/dl (7.76
      mmol/l) and those under the age of 65 years. In women the cost-effectiveness was
      lower than 10 million of pesetas per year of life gained in those presenting more
      than 340 mg/dl (8.79 mmol/l) under the age of 65 years. CONCLUSIONS: The results
      of this study demonstrate that the administration of lovastatine at 0.02 g/day is
      the most effective hypolipemiant treatment in preventing coronary heart disease.

PMID- 7500686
TI  - [Thrombocytopenia onset in acute episodes of pancreatitis].
AB  - BACKGROUND: The objective of this study was to determine the prevalence of
      thrombocytopenia in acute pancreatitis and its value as a prognostic marker for
      complications. METHODS: The records of all patients admitted to our institution
      between January and June 1993 were reviewed. After exclusion of other possible
      causes of thrombocytopenia, 104 patients were evaluated. The prognostic value of
      thrombocytopenia was determined by evaluation of the length of hospital stay,
      radiologic severity, complications, need for ICU care, need for surgery and
      mortality. RESULTS: The etiology of pancreatitis was as follows: gallstone
      induced in 49 patients, alcoholic in 35, idiopathic in 12 and due to other causes
      in the remaining 8 cases. Thrombocytopenia developed early, within the first 48
      hours and was moderate (106 +/- 27 x 10(9)/l). Alcoholic pancreatitis was
      associated to a higher probability to develop thrombocytopenia (43% vs 36% in
      gallstone-induced pancreatitis and 4% in idiopathic pancreatitis, p = 0.02).
      Thrombocytopenic patients had a greater radiologic severity (Balthazar's scores D
      or E 78% vs 49%, p = 0.04), a higher number of acute complications (28% vs 10%, p
      = 0.05) and a more frequent need for ICU care (25% vs 7%, p = 0.01). No
      differences were seen in length of hospital stay, need for surgery and mortality
      between the two groups of patients. CONCLUSIONS: Thrombocytopenia is frequent in
      acute pancreatitis, especially in cases of alcoholic origin. Its presence
      suggests a higher risk to develop complications.

PMID- 7500687
TI  - [Life style and cardiovascular risk factors].

PMID- 7500688
TI  - [Acarbose and diabetes. Slight improvement or authentic therapeutic progress?].

PMID- 7500689
TI  - [Drug nomenclature (I). What is the international common terminology and what is
      its use?].

PMID- 7500690
TI  - [Cytologic and biochemical characteristics of breast fluid obtained through the
      nipple of non-lactating women].

PMID- 7500691
TI  - [The prolonged use of non-depolarizing muscle relaxants].

PMID- 7500692
TI  - [Family consent in organ donations].

PMID- 7500693
TI  - [Antiphospholipid antibodies and Q fever].

PMID- 7500694
TI  - [C virus in organ donors].

PMID- 7500695
TI  - [Primary community care in Finland: no evident advantages for democracy and
      efficiency].

PMID- 7500696
TI  - ["Standards" or "norms" in quality assurance?].

PMID- 7500697
TI  - [Bayer and calcium blockers].

PMID- 7500698
TI  - [Closure of the old psychiatric hospitals is justified].

PMID- 7500700
TI  - [Physician--cure thyself!].

PMID- 7500699
TI  - [Free prescription right--a chimera?].

PMID- 7500701
TI  - [Respond immediately to requests by the insurance authority!].

PMID- 7500702
TI  - [TUV-p is a logical name for the new treatment of prostatic hypertrophy].

PMID- 7500704
TI  - [Shorter working hours for better occupational environment].

PMID- 7500703
TI  - [Chemical control is necessary for eradication of malaria].

PMID- 7500705
TI  - [Reasons for mandatory psychiatric internship].

PMID- 7500706
TI  - [Antibiotics in pneumonia may be changed without clinical examination].

PMID- 7500707
TI  - [Why is the number of visits to district physicians increasing?].

PMID- 7500708
TI  - [Fatal myocardial infarction: high risk for diabetics].

PMID- 7500709
TI  - [Defecography and its clinical significance. Increased use of an "old"
      technique].

PMID- 7500710
TI  - [Acute myocardial infarction after cytostatic therapy].

PMID- 7500711
TI  - [Visions on endogenous "antibiotics". Bright future of vaccines with new
      targets].

PMID- 7500712
TI  - [Valuable methods for lung function measurements. Spirometry at ambulatory
      centers is excellent for early diagnosis].

PMID- 7500714
TI  - [The 7th congress on dermatology and psychiatry. Bodily contact promotes peace of
      mind].

PMID- 7500713
TI  - [Female circumcision opposed in Haninge].

PMID- 7500715
TI  - [If the patient has ventricular septal defect: ambiguous fever may be indication
      of right-sided endocarditis].

PMID- 7500716
TI  - [The man behind the "maladie de Roger". The discoverer of ventricular septal
      defect].

PMID- 7500717
TI  - [Instruction and equality in medical research. Sex-related obstacles after equal
      education].

PMID- 7500718
TI  - [Global climate change on the way. Warning signals at an international meeting].

PMID- 7500719
TI  - [False safety with homeopathic agents. Swedes became ill with malaria in spite of
      prophylaxis].

PMID- 7500720
TI  - Macri update.

PMID- 7500721
TI  - The Consortium.

PMID- 7500722
TI  - Nurse in profile. Interview by Peter Schwab.

PMID- 7500723
TI  - Medication incident reporting forms.

PMID- 7500724
TI  - Reporting occupational injuries, illnesses and serious incidents.

PMID- 7500726
TI  - Guide to genetics services information.

PMID- 7500725
TI  - Care today--hope tomorrow. Genetic disorders.

PMID- 7500727
TI  - Open letter from the Disability Discrimination Commissioner.

PMID- 7500728
TI  - Midwifery and the Nurses Act 1991.

PMID- 7500729
TI  - Who cares for the carers?

PMID- 7500730
TI  - Pre-employment and pre-placement medicals--discrimination and confidentiality.

PMID- 7500731
TI  - Creative diversional activities.

PMID- 7500732
TI  - Admission and caring for the surgical breast cancer patient.

PMID- 7500733
TI  - Aromatherapy and its application in the management of people with dementia.

PMID- 7500734
TI  - The future of nursing and you.

PMID- 7500735
TI  - APHEDA study tour. A chance to go to Vietnam--yes please!

PMID- 7500736
TI  - Nurse in profile.

PMID- 7500737
TI  - Myth, magic and meaning. The magic of nursing--from witches and warriors to
      workers and wonderers.

PMID- 7500738
TI  - Myth, magic and meaning. Integrative medicine--the way of the future.

PMID- 7500739
TI  - Myth, magic and meaning. In search of good health.

PMID- 7500740
TI  - Glaucoma: the silent thief of sight.

PMID- 7500741
TI  - Professional development: the course to take.

PMID- 7500742
TI  - Sensible alerts.

PMID- 7500745
TI  - Cardiologists in casualty?

PMID- 7500744
TI  - Waiting for coronary artery bypass surgery: abusive, appropriate, or acceptable?

PMID- 7500743
TI  - Third-generation oral contraceptives: how risky?

PMID- 7500746
TI  - Where sensors lead.

PMID- 7500747
TI  - Sick library syndrome.

PMID- 7500748
TI  - Venous thromboembolic disease and combined oral contraceptives: results of
      international multicentre case-control study. World Health Organization
      Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
AB  - The composition and use of oral contraceptives (OCs) have changed since their
      cardiovascular side-effects were established 20 years ago. This report describes
      the risk of idiopathic venous thromboembolic (VTE) events (deep vein thrombosis
      [DVT] and/or pulmonary embolism [PE]) in association with current use of combined
      OCs among 1143 cases aged 20-44 and 2998 age-matched controls, as evaluated in a
      hospital-based, case-control study in 21 centres in Africa, Asia, Europe, and
      Latin America. OC use was associated with an increased risk of VTE in Europe
      (odds ratio 4.15 [95% CI 3.09-5.57]) and in non-European ("developing") countries
      (3.25 [2.59-4.08]). Risk estimates were generally higher for DVT than for PE but
      no consistent trend by certainty of diagnosis (definite, probable, possible) was
      found. Increased risk was apparent within 4 months of starting OCs, was
      unaffected by duration of current episode of OC use, and had disappeared within 3
      months of stopping OCs. Relative risk estimates of VTE associated with OC use
      were unaffected by age of user, by history of hypertension (excluding
      hypertension in pregnancy), or in any consistent way by smoking. However, in both
      groups of countries increased body mass index (BMI) was an independent risk
      factor for VTE, and OC-associated odds ratios were higher among those with a BMI
      above 25 kg/m2 than among those with smaller BMIs. OC-associated risk estimates
      were high among women in Europe with a history of hypertension in pregnancy. Odds
      ratios associated with the use of OCs containing a third-generation progestagen
      were higher than those observed with progestagens of the first (norethindrone
      type) and second (norgestrel group) generation. Odds ratios associated with first
      and second generation progestagens tended to be lower, though not significantly,
      when used in combination with low (< 50 micrograms oestrogen) rather than higher
      oestrogen doses. This study confirms an association between OC use and VTE in
      Europe and the developing countries, although overall risk estimates associated
      with use were lower than demonstrated in most previous studies of non-fatal
      idiopathic VTE.

PMID- 7500749
TI  - Effect of different progestagens in low oestrogen oral contraceptives on venous
      thromboembolic disease. World Health Organization Collaborative Study of
      Cardiovascular Disease and Steroid Hormone Contraception.
AB  - A multinational hospital-based case-control study of the risk of venous
      thromboembolic disease associated with combined oral contraceptives (OCs) done in
      1989-93 prompted a separate inquiry comparing the risk of venous thromboembolism
      (VTE) associated with low oestrogen (< 35 micrograms ethinyloestradiol) OCs
      containing levonorgestrel with risks in low oestrogen preparations containing the
      third-generation progestagens desogestrel or gestodene. This analysis of data
      from 9 countries, involved 769 cases and 1979 age matched hospital controls and,
      in one centre, 246 community controls matched on age and general practice. 137
      cases and 203 controls were current users of levonorgestrel (odds ratio [OR with
      95% confidence interval] 3.5 [2.6-4.7]), with non-users as the reference; 35
      cases and 28 controls were current users of desogestrel (9.1 [4.9-17.0]), and 36
      cases and 28 controls were current users of gestodene (9.1 [4.9-16.7]). The
      ratios of these risks, compared with levonorgestrel, were 2.6 (1.4-4.8) for both
      products separately. Risk estimates adjusted for body mass index (BMI) were 3.4,
      7.3, and 10.2 for levonorgestrel, desogestrel, and gestodene, respectively,
      compared with non-users, and 2.2 and 3.0 for desogestrel and gestodene,
      respectively, compared with levonorgestrel. 48 (68%) cases and 48 (86%) controls
      exposed to desogestrel or gestodene were from the UK (Oxford region). In this
      centre risk estimates compared with non-users, adjusted for BMI, were 2.6, 5.3,
      and 5.7 for levonorgestrel, desogestrel, and gestodene, respectively. Current
      users of low oestrogen dose combined OCs containing desogestrel or gestodene
      appear to be at higher risk of VTE than users of combined OCs containing
      levonorgestrel. The possibility that these unexpected results on a secondary
      study objective are due to chance, bias, or residual confounding cannot be
      excluded entirely and the results need to be confirmed by independent studies.
      They are at variance with the apparently more favourable metabolic effects of the
      newer progestagens. Whether the new progestagens are associated with lower risk
      of arterial disease (stroke and myocardial infarction) must be evaluated further.

PMID- 7500750
TI  - Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in
      women using oral contraceptives with differing progestagen components.
AB  - Concern about the risks of cardiovascular illness in women using combined oral
      contraceptives (OC) containing the progestagens desogestrel and gestodene
      prompted two studies of data from the UK General Practice Research Database. We
      compared the risks of certain cardiovascular illnesses in otherwise healthy women
      exposed to one of three OCs containing < 35 micrograms oestrogen plus
      levonorgestrel, desogestrel, or gestodene. In the first study, based on some 470
      general practices, there were 15 cases of unexpected idiopathic cardiovascular
      death among 303,470 women who were current users of one of the study OCs. The
      estimated incidence rates were 8/184,536 (4.3 per 100,000) woman-years at risk
      for users of combined OCs containing levonorgestrel, 2/135,567 (1.5 per 100,000)
      for desogestrel users, and 5/105,201 (4.8 per 100,000) for gestodene users. The
      relative risk (RR) estimates were 0.4 (95% CI 0.1-2.1) and 1.4 (CI 0.5-4.5) for
      desogestrel and gestodene, respectively, compared with levonorgestrel. In the
      second study, derived from some 370 general practices, there were 80 cases of
      nonfatal venous thromboembolism (VTE) in a cohort of 238,130 otherwise healthy
      women. The incidence rates of VTE per 100,000 woman-years at risk were 16.1 for
      levonorgestrel users, 29.3 for desogestrel, and 28.1 for gestodene. The adjusted
      RR estimates from the cohort analysis were 1.9 (1.1-3.2) and 1.8 (1.0-3.2) for
      desogestrel and gestodene users, respectively, compared with users of
      levonorgestrel. In a nested case-control analysis the adjusted matched RR
      estimates were 2.2 (1.1-4.4) and 2.1 (1.0-4.4) for desogestrel and gestodene
      users, respectively, compared with users of levonorgestrel. The excess risk for
      nonfatal VTE associated with the new generation of combined OCs containing low
      dose oestrogen and the progestagens desogestrel or gestodene compared with
      levonorgestrel is estimated to be 16 per 100,000 woman-years.

PMID- 7500751
TI  - Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis
      associated with oral contraceptives containing a third-generation progestagen.
AB  - Recent concern about the safety of combined oral contraceptives (OCs) with third
      generation progestagens prompted an examination of data from a population-based
      case-control study (Leiden Thrombophilia Study). We compared the risk of deep
      vein thrombosis (DVT) during use of the newest OCs, containing a third-generation
      progestagen, with the risk of "older" products. We also investigated the
      influence of family history of thrombosis, previous pregnancy, age, and the
      thrombogenic factor V Leiden mutation. We selected 126 women with DVT and 159
      controls aged 15-49 (mean age 34.9) and premenopausal and found, as compared with
      non-users, the highest age-adjusted relative risks to be that for an OC
      containing desogestrel and 30 micrograms ethinyloestradiol (relative risk [RR]
      8.7, 95% CI 3.9-19.3). We found lower relative risks for all other types of OC,
      ranging from 2.2 to 3.8. In a direct comparison, users of the desogestrel
      containing oral contraceptive had a 2.5-fold higher risk (95% CI 1.2-5.2) than
      users of all other OC types combined. The relative risk for the desogestrel
      containing OC was similar among women with and without a family history--ie,
      preferential prescription because of family history cannot explain our findings.
      Nor could the excess risk be explained by previous pregnancy, and it was highest
      in the youngest age categories, where we would expect most new users. The age
      adjusted RR for the desogestrel-containing contraceptive was 9.2 (3.9-21.4) among
      non-carriers of the factor V Leiden mutation and 6.0 (1.9-19.0) among carriers of
      the mutation. This latter risk is superimposed on the 8-fold increased risk of
      venous thrombosis for carriers of the factor V Leiden mutation. The risk of
      carriers using the desogestrel-containing OC as compared with noncarrier non
      users will therefore be increased almost 50-fold. Use of low-dose OCs with a
      third-generation progestagen carries a higher risk of DVT than the previous
      generation of OCs. The absolute risk of DVT associated with these OCs seems to be
      especially high among carriers of the factor V Leiden mutation and among women
      with a family history of thrombosis. However, the higher risk associated with OC
      with a third-generation progestagen compared with previous generations was also
      present in women without factor V Leiden and with no family history.

PMID- 7500752
TI  - Efficacy of traction for non-specific low back pain: a randomised clinical trial.
AB  - Previous trials to assess the efficacy of lumbar traction for back pain have been
      methodologically flawed. To avoid these shortcomings, we conducted a randomised
      controlled trial in which high-dose traction was compared with sham traction. The
      sham traction was given with a specially developed brace that tightens in the
      back during traction. To the patient, the experience is that of traction. The
      patients and outcome assessor were blinded for the assigned treatment. 151
      patients with at least six weeks of non-specific low back pain were randomised.
      Intention to treat analysis showed no differences between the groups on all
      outcome measures (patients' global perceived effect, severity of main complaints,
      functional status and pain); all 95% confidence intervals included the value
      zero. The number of withdrawals from treatment, loss to follow-up, and protocol
      deviations was low. Consequently, the per-protocol analysis showed results
      similar to the intention to treat analysis. Subgroup analyses did not show any
      group for which traction might seem promising. Our data do not support the claim
      that traction is effective for patients with low back pain.

PMID- 7500753
TI  - Is Kaposi's-sarcoma-associated herpesvirus detectable in semen of HIV-infected
      homosexual men?
AB  - We explored a possible route of transmission of Kaposi's-sarcoma-associated
      herpes virus (KSHV) with nested and unnested PCR techniques. We looked for KSHV
      DNA sequences in semen of HIV-positive homosexual men and HIV-negative healthy
      semen donors. With unnested primers we found KSHV sequences in 21 of 33 (64%)
      homosexual men and in none of 30 healthy donors. With a nested PCR assay, 30 of
      33 (91%) specimens from the homosexual men and 7 of 30 (23%) specimens from
      healthy donors had detectable KSHV sequences. Over 5 years of follow-up, 13 of 30
      KSHV-positive homosexual men (43%) developed KS compared with none of the 3 KSHV
      negative homosexual men.

PMID- 7500754
TI  - A young woman with hepatitis after a sore throat.

PMID- 7500755
TI  - Severe septic shock unresponsive to noradrenaline.

PMID- 7500756
TI  - Waiting for coronary artery bypass surgery: population-based study of 8517
      consecutive patients in Ontario, Canada. The Steering Committee of the Adult
      Cardiac Care Network of Ontario.
AB  - Deaths and delays in queues for coronary surgery in Canada have been highlighted
      by American interest groups opposed to "socialized medicine". Since 1991 all nine
      cardiac surgery centres in Ontario register and follow patients after acceptance
      for surgery. We examined the experience of 8517 consecutive patients leaving the
      registry from October 1991 to July 1993. Individual acuity scores were determined
      based on symptoms, angiographic findings, left ventricular function, and, where
      available, non-invasive tests of ischaemic jeopardy. Planned surgery was declined
      or deferred for 3.2% of registrants. While in the queue, 31 (0.4%) patients died
      and three had surgery indefinitely deferred after a non-fatal myocardial
      infarction. Among 8213 patients receiving surgery, the median wait was 17 days
      (inter-quartile range [IQR]: 4, 51), ranging from one day (IQR 0:4) for patients
      needing very urgent surgery (acuity score 2-3) to 42 days (IQR: 18, 77) for those
      rated low priority (acuity score 6-7). In a multivariate analysis, the most
      important determinant of waiting time was symptom status (p < 0.001), followed by
      anatomy (p < 0.001). Age did not alter waiting time; depending on statistical
      methods, female sex was either not significant or independently associated with
      approximately 11% relative delay (p = 0.001). Whether controlling for significant
      clinical factors or the multifactorial acuity scores, waiting times clearly
      varied (p < 0.001) among hospitals. We conclude that, during 1991-93, patients
      queuing for coronary surgery in Ontario rarely suffered critical events or
      extreme delays, and individual variation in waiting times primarily reflected
      clinical acuity. Nonetheless, symptoms provoked by very modest exertion were
      commonplace in the queue, and waiting times did vary inequitably among hospitals.

PMID- 7500757
TI  - Revising the research record.

PMID- 7500759
TI  - Gene therapy: caution and hope.

PMID- 7500758
TI  - Increased vulnerability of the subendocardium to ischaemic injury: an
      electrophysiological explanation.

PMID- 7500760
TI  - Is self-audit reliable?

PMID- 7500761
TI  - Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy.

PMID- 7500762
TI  - Plasma concentrations of obese protein in anorexia nervosa.

PMID- 7500763
TI  - Hypokalaemia related to acute chloroquine poisoning.

PMID- 7500764
TI  - Angioplasty versus bypass surgery.

PMID- 7500765
TI  - Langerhans cell phenotyping: a new tool for differential diagnosis of
      inflammatory skin diseases.

PMID- 7500766
TI  - Treatment of inoperable ovarian cancer with interleukin-2 and carboplatinum.

PMID- 7500768
TI  - Fertility drugs and breast and ovarian cancer.

PMID- 7500767
TI  - Fertility drugs and breast and ovarian cancer.

PMID- 7500769
TI  - Identifying areas at high-risk for neonatal tetanus.

PMID- 7500770
TI  - NSAIDs, Cox-2 inhibitors, and the gut.

PMID- 7500771
TI  - Mannose-binding protein genotypes and recurrent infection.

PMID- 7500772
TI  - Guidelines for treatment of hypertension.

PMID- 7500773
TI  - Screening blood donations for parvovirus B19.

PMID- 7500774
TI  - Maintaining confidentiality.

PMID- 7500775
TI  - Maintaining confidentiality.

PMID- 7500776
TI  - Misguided ethics committees?

PMID- 7500777
TI  - Suicide among Finno-Ugrians.

PMID- 7500778
TI  - Cost awareness in African hospitals.

PMID- 7500779
TI  - History of informed medical consent.

PMID- 7500780
TI  - Antimony detected in necropsy tissues may derive from contaminated formalin.

PMID- 7500781
TI  - Foodborne transmission of Cyclospora.

PMID- 7500782
TI  - Vitamin A status and dark green leafy vegetables.

PMID- 7500783
TI  - Vitamin A status and dark green leafy vegetables.

PMID- 7500785
TI  - 1342C mutation in Gaucher's disease.

PMID- 7500784
TI  - Decrease in glutamate in the jugular vein after head injury.

PMID- 7500786
TI  - ACE inhibitors and diabetics with albuminuria.

PMID- 7500787
TI  - ACE inhibitors and diabetics with albuminuria. The DIABHYCAR Study Group.

PMID- 7500788
TI  - Microemulsion formulation increases cyclosporin bioavailability in cystic
      fibrosis.

PMID- 7500789
TI  - In hot pursuit of MRSA.

PMID- 7500790
TI  - In hot pursuit of MRSA.

PMID- 7500791
TI  - HIV in the over-50s in south London.

PMID- 7500792
TI  - Dental caries with longterm use of antidepressants.

PMID- 7500793
TI  - [Tradition and progress in correction of large hernias].

PMID- 7500794
TI  - [Mesh reinforced cutis-plasty].
AB  - We report on 27 patients in whom a total of 28 augmented cutis plasties were
      performed to correct large hernias of the abdominal wall. After closure of the
      defect by cutis plasty an absorbable mesh is sutured at the fascia 2-3 cm away
      from the edge of the fascial defect. Postoperatively, 2 subcutaneous seromas had
      to be punctured. No wound infections were observed. After a first procedure (n =
      14) the recurrence rate was 7%, while after correction of recurrent hernias (n =
      14) there were 2 failures (14%). Augmentation by the mesh means that high initial
      stability of the abdominal wall is achieved, allowing transformation of the cutis
      into a strong fibrous tissue.

PMID- 7500795
TI  - [Angio-architecture of the colon in Crohn disease and ulcerative colitis. Light
      microscopy and scanning electron microscopy studies with reference to the
      morphology of the healthy large intestine].
AB  - The etiology and the pathogenesis of the chronic inflammatory bowel diseases
      known as Crohn's disease and ulcerative colitis have not been defined. Therefore,
      in this study the main emphasis was placed on description of the pathologic
      anatomy. Disturbed blood supply and vascular disorders have been discussed as
      etiopathogenetic factors. The results in the literature are frequently
      contradictory. For this reason, the vascular system of the colon in Crohn's
      disease and ulcerative colitis was systematically examined by means of various
      morphological methods in this study. Microvascular corrosion casting and
      translucent specimens were taken from operative specimens taken from 12 patients
      with Crohn's disease and 8 with ulcerative colitis. For comparison, tumor-free
      parts of 6 colon cancer specimens were examined. The evaluation was done by
      scanning electron- and/or stereoscopic microscopy. In the presence of chronic
      inflammatory bowel disease dilatation of the submucosal veins, caliber
      differences in the tunica muscularis and rarefaction of the penetrating blood
      vessels were found. In summary, an impairment of the blood flow in the tunica
      muscularis can be postulated. For the first time, the resulting venous stasis has
      been described, in contrast to the previously described disturbed arterial blood
      supply.

PMID- 7500796
TI  - [Need for thyroidectomy in differentiated thyroid cancers].
AB  - In a retrospective case series study we compared data collected from 142
      unselected patients with cancer of the thyroid gland treated in 1985-1994 with
      results from corresponding studies with reference to the necessity for radical
      thyroidectomy in cases of differentiated thyroid carcinoma. We standardly treated
      our patients by either primary or subsequent complete total thyroidectomy within
      48 h after initial surgery followed by 131I ablation, achieving an overall R0
      tumor clearance in 94.1% of cases. Recurrent laryngeal nerve palsy was diagnosed
      postoperatively in 7.7% of cases. Local tumor recurrence or nodal or distant
      spread occurred in 16.9% of patients with papillary, 9.1% of patients with
      follicular and 10% of patients with medullary carcinoma. Only one patient with
      papillary thyroid carcinoma died after 5 years at the age of 82, whereas 83% of
      anaplastic cancer patients died within 3 years. We conclude from our data that
      radical surgery ought to be performed for both differentiated thyroid cancer and
      undifferentiated cancer to reduce the rate of recurrence. When surgical
      management is careful radical thyroidectomy as standard treatment is associated
      with a reasonable rate of perioperative morbidity.

PMID- 7500797
TI  - [Spontaneous splenic rupture during portal triad clamping].
AB  - A 45-year-old woman underwent a resection for a hepatic metastasis of the liver
      caused by a carcinoma of the colon. Shortly after the Pringle maneuver severe
      hemorrhage from the upper left quadrant of the abdomen was observed. Exploration
      revealed a spontaneous parenchymal laceration of the spleen.

PMID- 7500798
TI  - Blood group antigen expression in malignant tumors of the thyroid: a parallel
      between medullary and nonmedullary carcinomas.
AB  - Blood group antigen (BGA) expression has been described in many fetal, adult, and
      tumorous tissues. Synthesis of BGA in the thyroid gland is regarded as oncofetal
      due to blood group structures that are detected in fetal and carcinomatous
      tissues but not in the normal adult organ. This study examined the prevalence of
      type 1 (CA-50, CA-19-9, Lea, Leb, A, B, H type 1) and type 2 (Le(x), Le(y), A, B,
      H type 2) antigens in normal thyroid (n = 25), papillary (n = 104), follicular (n
      = 52), anaplastic (n = 33), and medullary (n = 48) carcinomas of the thyroid.
      While normal thyroid tissue expressed no BGA, there was a significant increase of
      BGA expression in carcinomas of the thyroid gland. There are two theories about
      the possible origin of C cells, from which the medullary carcinomas arise. Some
      authors postulate that C cells belong to the amine precursor uptake and
      decarboxylation system and therefore derive from the neural crest, while others
      believe that C cells originate from the fifth pharyngeal pouch, as do the
      follicular cells. The results obtained in this study show that medullary and
      nonmedullary carcinomas correspond to one another in their BGA expression
      profile. Therefore it is concluded that medullary carcinomas may have the same
      origin as nonmedullary tumors of the thyroid.

PMID- 7500799
TI  - [Significance of therapy timing for the effects of systemic and local therapy
      with the ACE inhibitor captopril on intestinal microcirculation in manifest
      mesenteric ischemia. An animal experiment study in the swine].
AB  - We present the results of a study based on an animal model concurring whether
      captopril can improve microcirculation in the small intestine in nonocclusive
      mesenteric ischemia dependent on when therapy is begun. Cardiogenic shock was
      produced by pericardial tamponade with starch solution. The flow in the carotid
      artery could be reduced to 43% of the preshock value. In four therapy groups and
      a control group the intestinal microcirculation was examined by laser Doppler
      flowmetry in the serosa and mucosa. The measurements were taken at regular
      intervals during the 4 h of the experiments. Captopril was either given
      systemically or locoregionally through the upper mesenteric artery. Therapy was
      given at the beginning of the shock or 1 h after induction of shock at a dosage
      of 0.25 mg/kg body weight as a bolus and continuous application of 10
      micrograms/kg body wt. Concerning the hemodynamic changes during shock the group
      receiving captopril systemically at the beginning of shock showed a significant
      (P = 0.05) improvement in microcirculation compared to the controls and other
      therapy groups. Flow reduction was seen in the controls (156-32 relative flow
      units = RFU) in group Ia (systemic therapy 1 h after shock), as well as the
      controls (129 to 12 RFU) and, in group Ib (systemic therapy beginning with shock)
      a flow rise could be seen (307 to 481 RFU). In group IIa (local therapy 1 h after
      shock) (a steady flow was seen (168-170 RFU) and in group IIb (local therapy
      beginning with shock) and group Ib an increase in flow was also measured (226-303
      RFU). This positive effect of captopril on the intestinal perfusion was observed
      when applied 1 h after the induction of shock.

PMID- 7500801
TI  - [Diagnosis and surgical therapy of right-sided colonic diverticulitis].
AB  - Diverticulosis of the colon is common in the descending and sigmoid part; the
      right colon is rarely involved. Inflammation of perforation of a cecal
      diverticulum is an uncommon condition that mimics acute appendicitis. The correct
      diagnosis is mostly made after operative exploration. Four cases were surgically
      treated between 1994 and 1995. Because of the severe inflammation, ileocecal
      resection or right hemicolectomy was necessary; in one case we performed a local
      excision. After removal of the inflamed mass the postoperative healing was
      uncomplicated. A malignancy could be histologically excluded in all cases. As in
      sigmoid diverticulitis, early resection seems to be a safe operative therapy.
      Laparoscopy can show the correct diagnosis before the laparotomy is carried out.
      Preoperative diagnostic measures, differential diagnosis and possible surgical
      procedures are discussed.

PMID- 7500802
TI  - [Modified cryopreservation of parathyroid gland tissue. Evaluation and comparison
      in an animal experiment].
AB  - A modified cryopreservation technique for parathyroid tissue was investigated in
      an animal model. The modified technique was compared with a previously described
      method [10, 11] using a programmed freezer and also with other simplified
      cryopreservation techniques [1, 8]. Total parathyroidectomy was performed in 90
      Sprague-Dawley rats, which were allocated to 7 groups. Group I had no
      autotransplantation (n = 10) and group II underwent immediate autotransplantation
      of one parathyroid gland (n = 17). In the other five groups of rats the
      parathyroids were cryopreserved and one gland was reimplanted after 10 days'
      storage in liquid nitrogen (LN) at -196 degrees C. The following techniques for
      cryopreservation of the parathyroid glands were used. Group III: immediate
      placement in LN, n = 7; group IV: immediate placement in a freezer at -20 degrees
      C, transfer to LN after 2 h, n = 12; group V: immediate placement in a freezer at
      -80 degrees C, transfer to LN after 2 h, n = 13, group VI: manually controlled
      freezing initially at a rate of 1 degree C/min to -25 degrees C, and subsequently
      at 10 degrees C/min to -70 degrees C before transfer to LN [8], n = 19, group
      VII: programmed freezing at a controlled rate of 1 degree C/min to -80 degrees C
      prior to transfer to LN [10, 11], n = 12. Serum calcium concentrations were
      determined over a period of 60 days. Furthermore, the individual difference in
      the calcium concentration was assessed for each rat on the basis of the calcium
      levels recorded preoperatively and at day 60.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500800
TI  - [Immunologic tolerance after experimental liver transplantation].
AB  - Allografts in the rat liver are rejected less vigorously than other primarily
      vascularized allografts; they show a better survival rate and induce donor
      specific unresponsiveness or tolerance in some donor-recipient combinations. This
      overview focuses on the immunologic mechanisms of this privileged status of liver
      allografts. A variety of possible mechanisms, such as generation of suppressor T
      cells, humoral factors and microchimerism, has been related to the observed
      hyporeactivity. A further analysis of these phenomena may enhance the development
      of clinical organ transplantation protocols that allow for establishment of donor
      specific unresponsiveness without the need for life-long immunosuppression.

PMID- 7500803
TI  - [Selective intraoperative cholangiography in laparoscopic cholecystectomy].
AB  - Routine use of intraoperative cholangiography during laparoscopic cholecystectomy
      is still widely advocated and standard in many departments; however, it is
      controversial. We have developed a new diagnostic strategy for the detection of
      bile duct stones. The concept is based on an ultrasound examination and on
      screening for the presence of six risk indicators of choledocholithiasis. A total
      of 120 patients undergoing laparoscopic cholecystectomy were prospectively
      screened for the presence of these six risk indicators: history of jaundice,
      history of pancreatitis, hyperbilirubinemia, hyperamylasemia, dilated bile duct,
      and unclear ultrasound findings. The sensitivity of ultrasound and intraoperative
      cholangiography in diagnosing bile duct stones was also evaluated. For the
      detection of bile duct stones, the sensitivity was 77% for ultrasound and 100%
      for intraoperative cholangiography. Twenty percent of all patients had at least
      one risk indicator. The presence of a risk indicator correlated significantly
      with the presence of choledocholithiasis (P < 0.01, chi-square test). The
      negative predictive value of the total set of risk indicators was 100%. Following
      our diagnostic concept, we would have avoided 80% of intraoperative
      cholangiographies without missing a stone in the bile duct. This study lends
      further support to the view that routine use of intraoperative cholangiography is
      not necessary.

PMID- 7500804
TI  - Mastoidectomy elimination.
AB  - Surgery that eliminates the open radical cavity takes three forms: obliteration
      (cavity fill-in, reconstruction (canal wall defect repair), or ablation (external
      canal closure). The evolution of each variety is reviewed in detail and a
      personal series of 240 cases is discussed. These included obliterations and
      reconstructions employing porous hydroxylapatite ceramic implants. Larger defects
      required Grote implants, but high facial ridge cases were managed with attic
      defect plates and limited canalplasty. Canal repair success rates improved with
      the use of the middle temporal flap to improve canal wall vascularity Residual
      cholesteatoma has been prevented by staged surgery, and recurrent disease has
      been virtually abolished by aggressive prevention techniques which employ drum
      reinforcement with finely shaven cartilage-perichondrium composite grafts.
      Ossiculoplasty procedures included 85 Plastipore columellas, 107 Oval-Top
      hydroxylapatite/Teflon columellas and, more recently, 17 Spanner malleus
      stapes/footplate assemblies. Earlier poor results have been succeeded by more
      satisfactory levels. Since 1990, the air-bone gap has been closed to within 10 dB
      in 33% of cases and to within 20 dB in 66% of cases. Studies using SPITE
      (surgical, prosthetic, infection, tissues, and eustachian) adverse indicators
      have demonstrated high levels of pathology in elimination cases, when compared
      with nonelimination series. The SPITE studies have also demonstrated the
      reduction of pathology levels by staged surgery. Elimination surgery now provides
      permanent relief from the problem cavity in all but a few cases.

PMID- 7500805
TI  - [It is not all gold, what glitters].

PMID- 7500806
TI  - [Risk of infection in endoscopy].
AB  - Infection is one of the hazards of endoscopic procedures. This long known risk
      has received major concern because of potential HIV infection. In the individual
      patient, both, patient related factors (such as the compromised host) and
      procedure related factors (such as tissue damage) determine the risk of
      infection. The potential for transmission of microorganisms from patient to
      patient or from the endoscopic equipment to the patient is reviewed. Common
      sources of infection and relevant microorganisms are listed. For prevention of
      transfer of infective agents through the contaminated endoscope the importance of
      thorough mechanical cleaning of the endoscope and adequate disinfection is
      stressed.

PMID- 7500807
TI  - [Long-term prognosis of chronic B and C viral hepatitis].
AB  - 146 patients (62 female, 84 male) with chronic hepatitis B and 80 patients (34
      female, 46 male) with chronic hepatitis C were regularly examined in 1 to 2 year
      intervals with an average follow-up period of 12 years (mean). Each time patients
      were evaluated by physical examination, routine laboratory data, immunological
      and serological testing, ultrasonography, and laparoscopy and/or percutaneous
      liver biopsy. No patient of the study underwent immunosuppressive or antiviral
      treatment at any time.-The average time data in years are given as the median
      value (mean). Chronic hepatitis B: Histologic diagnoses and their long-term
      prognosis: Chronic persistent hepatitis (CPH) on first biopsy: 10% of cases
      complete recovery after 15 years, 70% progression to chronic active hepatitis
      (CAH) after 5 years; CAH: 30% advanced remission/complete recovery 8 years after
      the first diagnosis of CAH, 40% progression to liver cirrhosis after 5 years;
      liver cirrhosis: 50% advanced remission/recovery 4 years after the first
      diagnosis of cirrhosis, 5% developed a hepatocellular carcinoma (HCC) 11 years
      after the first diagnosis of cirrhosis. Natural history: In the 11 years
      following initial diagnosis of HBV-infection spontaneous recovery was observed in
      49% of cases. In 3% of the patients the disease eventually caused death (1 x
      hemorrhage of oesophageal varices, 3x HCC after 14 to 20 years). Chronic
      hepatitis C: All patients were anti-HCV- and HCV-RNA-positive.-There was no
      spontaneous elimination of virus in any patient (maximal follow-up 27
      years).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500809
TI  - [Association of gastroesophageal reflux and chronic laryngitis].
AB  - There is some evidence from anglo-american clinical and experimental studies that
      gastro-esophageal reflux is more common in patients with laryngitis. Within the
      framework of an open study, 32 patients with reflux esophagitis and laryngitis
      were treated with 20 mg omeprazole daily. After 4 weeks at the latest, in all
      cases inflammation of the esophagus and larynx had healed completely and the
      patients were without complaints. Suggesting that reflux is the underlying
      etiology patients with laryngitis seem to benefit from omeprazole.

PMID- 7500808
TI  - [Special problems of benign stomach tumors].
AB  - Comparing with malignant lesions or peptic ulcers benign gastric tumors are rare.
      From 916 patients with gastric diseases, who underwent laparatomy between 1980
      and 1993 in the Surgical Department at the University of Cologne, we found only
      15 cases (1.6%) of benign gastric tumors. The most common benign tumor of the
      stomach are leiomyomas followed by adenomas. The majority of benign tumors are
      asymptomatic. Complaints as hemorrhage or pain are seen of large tumors.
      Gastroscopy is the most important examination in the diagnosis of benign gastric
      tumors. Endoscopic polypectomy should be carried out in those lesions still
      benign. Greater lesions or endoscopically incomplete excised polyps should be
      treated surgically. Mesenchymal tumors are difficult to estimate in their
      dignity. The treatment of choice is local surgical extirpation. The postoperative
      results are excellent.

PMID- 7500810
TI  - [Traumatic aneurysm of the superior mesenteric artery as the cause of massive
      upper gastrointestinal hemorrhage].
AB  - Vascular malformation and aneurysmal disease of visceral arteries usually exhibit
      diagnostic problems in upper GI bleeding. In the presented case recurrent massive
      bleeding caused by an superior mesenteric artery aneurysm was a serious
      diagnostic and therapeutic challenge. Interventional embolization of the
      sacciform aneurysm led to a successful treatment and a favourable outcome.

PMID- 7500811
TI  - [Splenic vein aneurysm: diagnosis with color-coded duplex ultrasound].
AB  - This is a report on a 67-year-old woman who was admitted to our department with a
      suspected pseudocyst of the pancreas as diagnosed by ultrasonography performed
      elsewhere. A percutaneous US study revealed an echo-free space-consuming process
      measuring 3 cm in diameter and located cranially to the pancreas. On the basis of
      colour Doppler sonography, a splenic vein aneurysm was diagnosed. An
      endosonographic examination clearly visualized the aneurysm. Colour Doppler
      sonographic examination is a valuable diagnostic procedure for the differential
      diagnosis of "cystic" space-consuming processes in the region of the pancreas.

PMID- 7500812
TI  - [Diagnostic measures before laparoscopic cholecystectomy].

PMID- 7500813
TI  - Deformities and disabilities--unfinished agenda in leprosy work.

PMID- 7500815
TI  - Relapse with multibacillary leprosy caused by rifampicin sensitive organisms
      following paucibacillary multidrug therapy.
AB  - Many leprosy patients treated with multidrug therapy (MDT) had previously
      received dapsone (DDS) monotherapy for many years. We report here 2 such patients
      treated with modified paucibacillary MDT composed of rifampicin and DDS who
      subsequently relapsed with multibacillary leprosy 5 and 6 years after release
      from treatment. Isolates of Mycobacterium leprae from both patients were
      resistant to DDS but sensitive to rifampicin, suggesting that the relapses were
      caused by rifampicin sensitive 'persister' organisms. The implications of this
      for surveillance of patients released from treatment (RFT) and the management of
      relapsed patients is discussed.

PMID- 7500814
TI  - Role of reactive oxygen species in renal damage in experimental leprosy.
AB  - Renal involvement is known to occur in leprosy. In the present study the possible
      role of reactive oxygen species (ROS) in causation of renal damage in mice
      infected with Mycobacterium leprae has been investigated. At least six animals
      from each group (control and infected) were killed at 0 day, 3, 6 and 9 months
      postinfection. The results showed a significant increase in the chemiluminescence
      (CL) response of peritoneal macrophages which was maximum between 3 and 6 months.
      No significant increase was observed in CL response of blood neutrophils. A
      significant increase in lipid peroxidation was observed at 3 and 6 months as
      evident by an increase in malondialdehyde levels. The increased ROS production
      might be the cause of lipid peroxidation. The renal damage is alos evident by
      decrease in the activity of renal brush border membrane enzymes, namely, alkaline
      phosphatase, leucine aminopeptidase and r-glutamyl transpeptidase. Thus ROS might
      play a role during early stages of M. leprae infection but in the later stages
      other immunological mechanisms may overpower the effect of ROS.

PMID- 7500817
TI  - Current concepts in the surgical management of lagophthalmos in leprosy.
AB  - Existing data suggest that, at a minimum, 2% of paucibacillary patients and 5% of
      multibacillary patients have lagophthalmos; at least 290,000 people worldwide
      have leprosy-related lagophthalmos. Surgical intervention is the only method for
      correcting lagophthalmos; effectiveness of the different procedures commonly used
      has not been measured. Results from a survey of eye care providers revealed that
      surgeons in Asia used a wide range of different techniques for the correction of
      lagophthalmos while almost all of the surgeons in Africa used tarsorrhaphy. There
      is a need to evaluate surgical outcome of these techniques and to develop
      guidelines to assist in increasing the number of surgeries for lagophthalmos in
      leprosy patients.

PMID- 7500816
TI  - Lagophthalmos in a multibacillary population under multidrug therapy in the
      People's Republic of China.
AB  - Lagophthalmos may be the most common potentially blinding ocular condition in
      leprosy. The magnitude of the problem among multibacillary patients has not been
      determined. We sought to ascertain the magnitude of lagophthalmos in a
      multibacillary leprosy patient population under multidrug therapy (MDT) (both
      newly diagnosed and with a prior history of dapsone monotherapy) in China and
      assess factors associated with its presence. In a survey of 640 multibacillary
      patients 3.8% of the newly diagnosed patients and 10.2% of the patients with
      prior dapsone monotherapy had lagophthalmos. Corneal disease and vision loss were
      common in both groups. Poor compliance with MDT, duration between onset and
      diagnosis, and duration on dapsone monotherapy were associated with the presence
      of lagophthalmos. Our findings suggest that there may be a threshold at which MDT
      must be maintained to prevent lagophthalmos. Early leprosy diagnosis and
      treatment would also lessen the incidence of lagophthalmos in these patients. The
      high proportion of lagophthalmos patients with corneal disease suggests that
      there has been inadequate eye care for these patients.

PMID- 7500818
TI  - Repeatability of nerve thickness assessment in the clinical examination for
      leprosy.
AB  - The assessment of the thickness of the superficial peripheral nerve trunks to
      document nerve involvement is an important aspect of clinical examination in case
      finding for leprosy, and is usually done by trained paramedical workers (PMWs).
      This assessment is subject to variability and has implications on the outcome of
      the survey. The present study proposes to quantify this variability. In this
      study, 242 individuals, consisting of 50 neuritic cases, 143 nonneuritic cases of
      leprosy and 49 normal controls, selected from the records of the trial of BCG
      prophylaxis in leprosy in South India, were examined by a doctor and paramedical
      workers. Repeatability of nerve thickness assessment for ulnar and popliteal
      nerves between the medical officer (MO) and the PMWs was quantified using Kappa
      statistics. The Kappa values for repeatability between the MO and the PMWs ranged
      from 0.45 to 0.54 and 0.52 to 0.69 for ulnar and popliteal nerves, respectively.
      The implications of the variability in nerve assessment are discussed.

PMID- 7500819
TI  - Tibialis posterior transfer in the correction of footdrop due to leprosy.
AB  - In the correction of footdrop due to leprosy neuritis the tibialis posterior
      muscle is re-routed and used to provide dorsiflexion of the foot. This study of
      tibialis posterior transfer was carried out to compare the results of the
      circumtibial and interosseous routes. There is no significant difference in the
      range of motion between either route through the range of the interosseous route
      is more functional (better dorsiflexion). The interosseous route is preferable as
      this results in a significantly lower incidence of recurrent inversion deformity
      of the foot at long-term follow-up when compared with the circumtibial route.

PMID- 7500820
TI  - Hand wounds in leprosy patients.
AB  - This study assessed the causes, duration and site of hand wounds seen among
      patients in order to try and improve the delivery of self-care teaching to
      patients with anaesthetic hands. Seventy-seven patients with 102 affected hand
      surfaces were assessed. The commonest cause was a burn from a tea glass. The
      average duration of the wound was 2 weeks. Most patients had a single current
      wound and 62% of wounds were on the palmar surface.

PMID- 7500821
TI  - Problems, acceptance and social inequality: a study of the deformed leprosy
      patients and their families.
AB  - Though the impact of social inequality on health conditions is widely known, its
      impact on the chronic and stigmatized disease, leprosy, has received little
      attention. Deformity sometimes leads to disabilities and to handicaps causing
      problems to the patient and his family. In this paper an attempt has been made to
      understand the impact of social inequality, prevalent in the form of the caste
      system in India on the deformed leprosy patients and on their families. This
      impact was examined in terms of the problems faced by the patients. A sample of
      150 deformed patients and their families, drawn from two districts in Tamil Nadu,
      was selected for the study. About 57% of the deformed patients experienced their
      deformity as a handicap which caused social and economic problems while the rest
      did not. Of the three caste groups, the Lower Caste group experienced more severe
      economic problems while the Upper Caste group faced more social problems. The
      extent of acceptance of deformed patients in their family varied significantly
      among those facing and not facing problems due to their deformity. The deformed
      patients without any handicap were accepted in a large majority of their families
      (82%) regardless of their caste status. In contrast the deformed but handicapped
      patients were accepted differentially among the three caste groups with the Upper
      group accepting them in most of their families (80%) while in the Lower group
      much less number of families (54%) did. All the families of the deformed but not
      handicapped patients desired to keep their patients till their death irrespective
      of their caste status. On the contrary, while all the families in the Upper Caste
      group expressed their willingness to keep their handicapped patients in the
      family till their death, 10% in the Middle and 22% in the Lower Caste groups did
      not want to do so. This suggests the gradual marginalization, rejection and
      dehabilitation of the affected. Thus, one's caste status can be a broad indicator
      of the nature and the extent of handicaps and acceptance in the family. This
      factor needs to be appropriately taken care of for rehabilitation and disability
      management in leprosy control programmes.

PMID- 7500822
TI  - Post-kala-azar dermal leishmaniasis mimicking leprosy: experience with 4
      patients, with some unusual features in 1.
AB  - We report on 4 cases of post-kala-azar dermal leishmaniasis (PKDL). History of
      kala-azar was available in all 4 patients. Slit-skin smears (SSS) for leishmania
      donovani (LD) bodies were negative in all 4. In 3 patients hypopigmented lesions
      were present over the face. Papules and nodules over his lips, tongue, scrotum
      and dactylitis were some unusual features observed in 1 patient.
      Histopathological examination showed LD bodies in 2 patients; histopathology was
      nonspecific in the other 2. All the patients were treated with sodium
      stibogluconate, 20 mg/kg/day. Infiltrated papules and nodules had subsided by 3
      months, while hypopigmented macules took longer to improve. In 3 patients there
      had previously been a misdiagnosis as leprosy sufferers and they had been treated
      with antileprosy drugs. Clinical and histopathological differences between PKDL
      and leprosy are discussed.

PMID- 7500823
TI  - Protective footwear for leprosy patients with sole sensory loss or ulceration of
      the foot.

PMID- 7500824
TI  - Does loss of nerve function equal pure neuritic leprosy?

PMID- 7500825
TI  - Recording of the disability index.

PMID- 7500826
TI  - Borderline lepromatous leprosy masquerading as lymphocutaneous sporotrichosis.

PMID- 7500827
TI  - Pentoxifylline may be useful in the treatment of type 2 leprosy reaction.

PMID- 7500828
TI  - TB. A global emergency, WHO, July 1994.

PMID- 7500829
TI  - Photoperiodic exposure and time of day modulate the expression of arginine
      vasopressin mRNA and vasoactive intestinal peptide mRNA in the suprachiasmatic
      nuclei of Siberian hamsters.
AB  - In hamsters, changes in ambient photoperiod lead to alterations in the circadian
      rhythm of pineal melatonin secretion and subsequent changes in reproductive
      function. The present study examined whether photoperiod also alters 24-h rhythms
      in neuropeptide mRNA levels in the SCN of Siberian hamsters. In situ
      hybridization and quantitative autoradiography were used to assess messenger RNA
      levels for vasopressin (AVP) and vasoactive intestinal peptide (VIP) in the SCN
      of hamsters sacrificed at six times of day following exposure to long (16 h
      light/day) or short (10 h light/day) photoperiod for 2 weeks. Both AVP mRNA and
      VIP mRNA in the SCN were significantly affected by time of day and photoperiodic
      exposure. The 24-h profiles of AVP mRNA and VIP mRNA showed different
      relationships to the light: dark cycle, suggesting that these profiles are
      differentially regulated. In general, short photoperiod tended to suppress AVP
      mRNA and VIP mRNA in the SCN; this effect on AVP mRNA was significant at two
      times of day. These results complement and extend previous findings of 24-h h
      profiles in neuropeptide mRNA expression in the rat SCN by showing that these 24
      h profiles are also characteristic of the Siberian hamster SCN and that they can
      be modulated by photoperiod.

PMID- 7500830
TI  - Molecular characterization and isolation of a 45-kilodalton imidazoline receptor
      protein from the rat brain.
AB  - Imidazoli(di)nes bind to molecular entities different from alpha 2-adrenoceptors:
      the so-called imidazoline receptors (IRs). Two main types of IRs have been
      described, the clonidine- and the idazoxan-preferring types, as well as other IRs
      whose pharmacological properties do not fit either type, but little is known
      about the molecular features of these receptors. In this study, IR proteins have
      been solubilized from the rat brain, using the zwitterionic detergent CHAPS, and
      analyzed by pharmacological and immunological means two of the four peak
      discriminated by gel filtration chromatography using [3H]idazoxan binding and a
      specific antibody. The IR eluted in the first peak accounted for 80% of the
      specific binding of [3H]idazoxan to solubilized brain membranes, and its
      pharmacological features corresponded to the non-adrenoceptor component of
      [3H]idazoxan binding in rat brain native membranes. The elution volume of this
      peak corresponded to a 130-140-kDa protein, but immunoblot analysis with a
      specific anti-IR antiserum showed the presence of a approximate 45-kDa IR
      protein, suggesting that this receptor is either an oligomeric protein complex or
      that it is associated with other proteins. This result was in agreement with the
      isolation and immunodetection of a 45-kDa peptide by affinity chromatography,
      which supported the relationship between this protein and a rat brain imidazoline
      binding site. The second peak, accounting for 15% of the specific binding of
      [3H]idazoxan to solubilized membranes, had a Mr of approximately 65-70,000, as
      determined by gel filtration chromatography and immunoblotting.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7500831
TI  - Localization and functional coupling of HGF and c-Met/HGF receptor in rat brain:
      implication as neurotrophic factor.
AB  - Hepatocyte growth factor (HGF), a natural ligand for the c-met protooncogene
      product, has mitogenic, motogenic and morphogenic activities for various cell
      types and functions as a organotrophic factor for regeneration of the liver,
      kidney and lung. We obtained evidence that HGF may function as a novel
      neurotrophic factor in the central nervous system. Northern blot analysis showed
      that 6 kb HGF mRNA and 9 kb c-Met/HGF receptor mRNA are expressed in various
      regions of the adult rat brain. In situ hybridization analysis revealed that
      intense hybridization signals for HGF mRNA were localized in cerebral cortex,
      hippocampus and amygdala. Consistently, specific localization of HGF protein in
      neurons of these regions was detected by immunohistochemical analysis and non
      neuronal glial cells in cingulum, cerebellum, pons and medulla were also
      specifically stained. Specific intense hybridization signals for c-Met/HGF
      receptor mRNA were also widely distributed in the brain, including neurons of
      olfactory bulb, cerebral cortex, primary olfactory cortex, hippocampus and
      cerebellum. On the basis of the co-expression of HGF and c-Met/HGF receptor in
      hippocampal neurons, we found that HGF prolonged survival of embryonic
      hippocampal neurons in primary culture: HGF elicited maximal surviving effect at
      0.5-1 ng/ml and the potency was comparable to that of nerve growth factor. More
      importantly, expression of both HGF and c-Met/HGF receptor mRNAs was markedly
      induced in response to cerebral ischemic injury. We propose that HGF functions as
      a neurotrophic factor in the central nervous system and that this neurotrophic
      function may have a role in the survival and reconstruction of specific neurons
      in response to cerebral injury.

PMID- 7500832
TI  - Correspondence between sites of NGFI-A induction and sites of morphological
      plasticity following exposure to environmental complexity.
AB  - To determine if gene regulation may play a role in behaviorally-induced
      morphological plasticity in the brain, we used in situ hybridization to measure
      levels of mRNA for the immediate early gene transcription factor NGFI-A (also
      known as ZENK, zif/268, egr-1 and Krox 24). Brains of periadolescent male rats
      exposed to 2-4 days of the following behavioral treatments were compared: (1)
      group housing in a complex environment (EC); (2) individual housing with daily
      handling (HIC); and (3) individual handling (IC). Quantitative analysis of the
      autoradiograms revealed that EC rats had significantly higher levels of NGFI-A
      than IC rats in regions of cortex previously shown to exhibit morphological
      plasticity (most pronounced in visual cortex), but not in frontal cortex where no
      dendritic changes have been detected. HIC rats were intermediate between the two
      groups. These data support an association between structural plasticity and
      altered patterns of immediate early gene expression.

PMID- 7500833
TI  - Decreased expression of the alpha subunit of Ca2+/ calmodulin-dependent protein
      kinase type II mRNA in the adult rat CNS following recurrent limbic seizures.
AB  - Calcium/calmodulin-dependent protein kinase type II (CamKII) is a ubiquitous
      brain enzyme implicated in a wide variety of neuronal processes. Understanding
      CamKII has become increasingly complicated with the recent identification of
      multiple gene transcripts coding for separate subunits. Previous studies have
      shown that mRNA for the alpha subunit of CamKII can be increased by reduction of
      afferent input. In this study we have examined the regulation of alpha CamKII
      mRNA following increased activity due to seizures. Using in situ hybridization
      with a cRNA probe against the rat alpha CamKII sequence we found reduced levels
      of hybridization following limbic seizures induced by lesions of the hilus of the
      dentate gyrus. Hybridization was most dramatically reduced in the granule cells
      of the dentate gyrus and the pyramidal cells of hippocampal region CA1. There
      were also significant reductions in hybridization in the superficial layers of
      neocortex and piriform cortex. In each of these region hybridization was
      decreased in the molecular layers which is consistent with the reported dendritic
      localization of alpha CamKII mRNA. All changes in mRNA content were transient,
      with maximal reductions at 24 h following lesion placement and a return to
      control levels by 96 h. These findings demonstrate the negative regulation of
      alpha CamKII mRNA by seizure activity and raise the possibility that synthesis of
      this kinase may be regulated by normal physiological activity.

PMID- 7500834
TI  - Promoter activity of the gene encoding the beta-amyloid precursor protein is up
      regulated by growth factors, phorbol ester, retinoic acid and interleukin-1.
AB  - Abnormalities in gene regulation of the beta-amyloid precursor protein (beta APP)
      might be an important factor in the neuropathology of Alzheimer's disease. We
      analyzed the effects of nerve growth factor (NGF), basic fibroblast growth factor
      (bFGF), phorbol 12-myristate 13-acetate (PMA), interleukin-1 (IL-1) and retinoic
      acid (RA) on promoter activity of the beta APP gene. To investigate the effect of
      these factors on promoter activity, we used two fusion plasmids which contain
      sequences of -489 and -415 base pairs (bp), respectively, from the transcription
      start site of the beta APP gene. The truncated regions of the promoter wer linked
      upstream to a reporter gene, chloramphenicol acetyl transferase (CAT). Promoter
      activity was tested by transient transfection of fusion plasmids in PC12 cells
      using the electroporation method (960 microF at 350 V). We report that the
      treatment of PC12 cells with either NGF, bFGF, PMA, IL-1 or RA stimulated the
      activity of the beta APP promoter. The treatment of cells with either NGF or bFGF
      resulted in a higher degree of stimulation in the basal level of promoter
      activity than when cells were treated with either PMA, IL-1 or RA. The deletion
      of sequences between -489 to -416 bp had no significant effect on promoter
      activity. The treatment of cells with these factors for a duration of 4 days
      prior to transfection with the plasmids is necessary for the stimulatory effect.
      The cells that were only treated with any of these factors after transfection
      showed no significant change in the basal level of promoter activity. We conclude
      that certain growth factors and a cytokine could enhance the basal level of
      promoter activity of the beta APP gene, suggesting a possible participation of a
      growth-factor(s)-mediated transcription element in the control of gene expression
      of beta APP.

PMID- 7500835
TI  - The first intron of the mouse neurofilament light gene (NF-L) increases gene
      expression.
AB  - Neurofilament expression is developmentally and post-transcriptionally
      controlled. Using transient transfection assays in mouse L cells, we demonstrate
      that the expression of the mouse neurofilament light subunit (NF-L) is influenced
      by intron sequences. NF-L expression was decreased twenty fold upon deletion of
      the three intron sequences. Elements contained principally within a 350 bp region
      of intron 1 were responsible for enhanced NF-L expression. Enhancement of
      expression did not occur when intron I was placed 3' to a heterologous
      chloramphenicol acetyl transferase (CAT) gene whose expression was driven by NF-L
      5' sequences. The intron enhancement of NF-L expression was not promoter-specific
      and also occurred with the mouse sarcoma virus (MSV) LTR promoter. These data
      suggest intron sequences may be important in regulating NF gene expression.

PMID- 7500836
TI  - In situ hybridization of mRNA expression for IP3 receptor and IP3-3-kinase in rat
      brain after transient focal cerebral ischemia.
AB  - Loss of intracellular calcium homeostasis has been regarded an important factor
      underlying neuron cell death after cerebral ischemic insult. In the brain, a
      major mechanism for regulation of intracellular calcium is through the signal
      transduction pathway involving hydrolysis of poly-phosphoinositides and release
      of the second messenger, inositol 1,4,5-trisphosphate (IP3). IP3 mobilizes
      calcium by interacting with an intracellular receptor. Upon its release after
      agonist stimulation, this second messenger is catabolized by a 3-kinase and a 5
      phosphatase. In this study, in situ hybridization was carried out to examine the
      mRNA expression of IP3, receptor (IP3R) and IP3 3-kinase (IP3K) in rat brain
      cortex after transient focal cerebral ischemia induced by temporary occlusion of
      the middle cerebral artery (MCA) and the common carotid arteries (CCAs). Results
      indicate a large decrease (52%) in IP3R mRNA levels in the ischemic cortex as
      compared to that in the contralateral side at 4 h after a 45 min ischemic insult.
      By 16 h, practically no IP3R mRNA could be detected in the ischemic cortex. On
      the other hand, IP3K mRNA levels remained unaltered until 16 h after reperfusion,
      during which time, expression in the infarct core decreased but that surrounding
      the core area increased instead. Hybridization of adjacent brain sections with
      probes for neuron specific enolase (NSE) and beta-actin indicated also a time
      dependent decrease in mRNA levels after ischemia, but these changes were less
      dramatic as compared to IP3R. At 16 and 24 h after reperfusion, there was an
      increase in beta-actin mRNA in cortical areas outside the MCA cortex, suggesting
      of reactive gliosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500837
TI  - Chlordiazepoxide attenuates stress-induced activation of neurons, corticotropin
      releasing factor (CRF) gene transcription and CRF biosynthesis in the
      paraventricular nucleus (PVN).
AB  - Corticotropin-releasing factor (CRF) plays a role in coordinating endocrine,
      autonomic, and behavioral responses to stressful stimuli. Benzodiazepines exert
      many effects which oppose those of CRF, including anxiolysis and suppression of
      the pituitary-adrenal axis. In the present study, we employed in situ analysis of
      CRF heteronucleous RNA (hnRNA) and c-fos mRNA to assess stimulus-induced CRF gene
      transcription rate following stress and its modulation by chlordiazepoxide (CDP).
      Male albino rats were exposed to restraint stress for 30 min and sacrificed 30
      and 120 min after the onset of stress. Either CDP or vehicle was given
      intraperitoneally 60 min before stress. To determine plasma ACTH levels by
      immunoradiometric assay, another group of rats was decapitated 10 min after the
      onset of restraint stress. Restraint stress induced rapidly and significantly c
      fos mRNA and CRF hnRNA expression in the PVN at the 30 min time point. Increases
      in both RNA copies were significantly inhibited by administration of CDP at doses
      of 5 and 10 mg/kg. CRF mRNA concentrations were increased significantly in the
      PVN 120 min after stress and again, CDP attenuated significantly these increases
      in the PVN. The plasma ACTH increase in response to stress was inhibited
      significantly by CDP administration at every dose tested. CDP did not change CRF
      mRNA levels in the non-stressed animal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500838
TI  - Specific subunit mRNAs of the GABAA receptor are regulated by progesterone in
      subfields of the hippocampus.
AB  - The ability of ovarian steroids to regulate the excitability of hippocampal
      neurons may be mediated by alterations in the inhibitory activity of GABA. We
      assessed the ability of estradiol, progesterone, and 3 alpha-OH-5 alpha-pregnan
      20-one (3 alpha-OH-DHP; a metabolite of progesterone) to regulate gene expression
      of selected GABAA receptor subunits (alpha 1, alpha 2, beta 1, beta 2, and gamma
      2). Using in situ hybridization, we found that progesterone, or 3 alpha-OH-DHP,
      suppressed mRNA levels for the alpha 1 subunit in the CA2, CA3, and the dentate
      gyrus subfields of the hippocampus in animals that were pretreated with
      estradiol. Progesterone had a more limited effect on the alpha 2 subunit,
      suppressing mRNA levels in estradiol-primed animals only in the CA3 region. In
      contrast, progesterone increased mRNA levels for the gamma 2 subunit in the CA1,
      CA2, and CA3 regions of the hippocampus, but only in animals that were not
      estradiol-primed. Estradiol alone had no significant effect on the expression of
      any subunit examined. Beta 1 and beta 2 subunit mRNA levels were not altered by
      any of the hormones tested. These data support the conclusion that progesterone
      and its metabolites may regulate excitability of the hippocampus by modulating
      the GABAA receptor gene expression; these effects of progesterone are dependent
      upon the circulating levels of estradiol. Alterations in the gene expression of
      selective subunits may lead to changes in the density of GABAA receptor protein
      or to changes in receptor subunit composition which might alter receptor
      sensitivity to activation by GABA or modulators such as the benzodiazepines and
      convulsants.

PMID- 7500839
TI  - Clusterin accumulates in dying neurons following status epilepticus.
AB  - Clusterin is a protein that has been implicated in cell death and remodelling in
      a number of different tissues. To further investigate the role of clusterin in
      nerve cell death its expression was measured in the rat brain at various times
      after status epilepticus (SE) induced by 1 h of hippocampal stimulation, by using
      in situ hybridization, immunocytochemistry, and immunoblotting. SE lead to a
      dramatic time-dependent increase in clusterin mRNA in non-nerve cells resembling
      astrocytes in the hippocampus beginning after 24 h. There was also an earlier
      induction of clusterin mRNA in dentate granule cells, that survive SE. Only a low
      mRNA signal was observed over the CA1 pyramidal cells, which die after SE. In
      contrast to these mRNA results, massive clusterin-like immunoreactivity was
      observed in CA1 pyramidal cells and dentate hilar neurons (and both of these
      neuronal populations die after SE), but not in dentate granule cells. We
      speculate that astrocytes produce clusterin after SE and that the clusterin is
      then secreted and taken up by hippocampal neurons destined to die. Thus, the role
      of clusterin in nerve cell death/ regeneration warrants further investigation.

PMID- 7500840
TI  - Molecular cloning of a cDNA for the human inositol 1,4,5-trisphosphate receptor
      type 1, and the identification of a third alternatively spliced variant.
AB  - The Inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular calcium
      channel involved in coupling cell membrane receptors to calcium signal
      transduction pathways within the cell. We have cloned a cDNA for the human type 1
      inositol 1,4,5-trisphosphate receptor. The sequence contains the S2 splice site
      which appears to be the region most divergent between rat and human. We now
      report an additional alternatively spliced region in the coupling domain, that is
      9 amino acids long, which we term S3. Alternatively spliced forms are found in
      both human and rat. PCR analysis of brain and peripheral tissues from human and
      rat shows both transcripts of the type 1 inositol 1,4,5-trisphosphate receptor in
      all tissues. The long form predominates in most brain regions (except the
      cerebellum) while the short form predominates in peripheral tissues. The sequence
      of the longer form in human appears to create an additional consensus protein
      kinase C phosphorylation site.

PMID- 7500841
TI  - L-DOPA reverses altered gene expression of substance P but not enkephalin in the
      caudate-putamen of common marmosets treated with MPTP.
AB  - The mRNA levels encoding neuropeptides were measured in the caudate nucleus,
      putamen and nucleus accumbens of common marmosets exposed to 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine pyridine (MPTP). Motor deficits induced by MPTP
      treatment were characterized by akinesia, postural abnormalities and rigidity.
      Seven days after MPTP treatment, there was a marked increase in levels of
      enkephalin mRNA in the caudate nucleus and putamen. In contrast, the
      hybridization signal for substance P mRNA was reduced. Alterations in the mRNA
      encoding neuropeptides were similar but less extensive in marmosets at 18-50
      months following MPTP treatment. No significant changes in enkephalin or
      substance P mRNA in the nucleus accumbens were observed at either time. Treatment
      with L-DOPA plus carbidopa for 4 weeks reversed MPTP-induce motor deficits and
      other behavioural abnormalities. The decrease in substance P mRNA in the striatum
      of MPTP-treated animals was reversed by L-DOPA treatment and reached levels above
      those found in normal animals. In contrast, the increase in enkephalin mRNA in
      marmosets treated with MPTP was not altered by L-DOPA treatment. In the nucleus
      accumbens the levels of peptide mRNA were not affected by L-DOPA treatment. Loss
      of nigral dopamine cells in a primate species causes opposing alterations in the
      expression of enkephalin and substance P mRNA in the caudate nucleus and putamen.
      No changes were observed in the nucleus accumbens, which reflects the resistance
      of the mesolimbic neurons to MPTP toxicity. While the decrease in substance P
      mRNA was reversed by L-DOPA treatment, the increase in enkephalin mRNA was not.
      This may partly indicate the greater effect of L-DOPA on the direct GABA pathway
      compared to the indirect output pathway from the striatum.

PMID- 7500843
TI  - Effects of morphine on forskolin-stimulated pro-enkephalin mRNA levels in rat
      striatum: a model for acute and chronic opioid actions in brain.
AB  - Opioid agonists inhibit adenylyl cyclase in brain through Gi-coupled receptors.
      One potential biological role for this reaction would be to decrease pro
      enkephalin mRNA synthesis by decreasing intracellular cAMP levels and preventing
      stimulation of gene expression via the cAMP regulatory element (CRE). To
      determine whether such effects occur in vivo, rats were injected i.c.v. with a
      water-soluble analog of forskolin, 7-beta-deacetyl-7 beta[gamma-(morpholino
      butyryl] butyryl] forskolin (DMB-forskolin), to stimulate the CRE. Pro-enkephalin
      mRNA levels were assayed in striatum by Northern blot analysis. The treatment
      with the forskolin analog increased striatal pro-enkephalin mRNA levels
      approximately 2-fold in 4 h. When rats were injected with morphine (20 mg/kg
      i.p.) 1 h before DMB-forskolin administration, the stimulation of pro-enkephalin
      mRNA levels was eliminated. This acute effect of morphine was blocked by co
      administration with 10 mg/kg naloxone. When rats were chronically treated with
      morphine for 8 days, then injected with morphine (20 mg/kg i.p.) 1 h before DMB
      forskolin administration, the inhibitory effect of morphine was lost (i.e. DMB
      forskolin increased pro-enkephalin mRNA levels by 2 fold in either control and
      morphine-treated rats). These data not only demonstrate the in vivo relevance of
      opioid-inhibited adenylyl cyclase in the control of pro-enkephalin mRNA levels,
      but also show that this model is useful for studying how this signal transduction
      system is attenuated during the development of tolerance.

PMID- 7500842
TI  - Dexamethasone enhances level of GAP-43 mRNA after nerve injury and facilitates re
      projection of the hypoglossal nerve.
AB  - Application of dexamethasone was found to induce an enhanced expression level of
      mRNA encoding the growth associated protein (GAP-43) after peripheral nerve
      injury. Following hypoglossal nerve axotomy, a dexamethasone releasing pellet
      (1.5 mg released in 3 weeks) was placed near the transected nerve. GAP-43 mRNA
      was detected in the hypoglossal nucleus by non-radioactive in situ hybridization
      histochemistry using an alkaline phosphatase-labeled oligonucleotide probe. A
      significant elevation of GAP-43 mRNA level was observed 2 weeks after the
      transection in dexamethasone treated animals. This induction was not observed in
      the dorsal motor nucleus of vagus which expresses moderately high levels of GAP
      43 mRNA even without nerve injury. Although dexamethasone did not alter the
      maximum level of GAP-43 mRNA in the hypoglossal nucleus after nerve injury, it
      prolonged the period in which the mRNA expression remained elevated. This may be
      due to post-transcriptional effect by the glucocorticoid. Dexamethasone treatment
      also caused a slight facilitation of reprojection. This may be due to the
      enhancement of GAP-43 mRNA level by the glucocorticoid.

PMID- 7500844
TI  - Immunocytochemical localization of nicotinic acetylcholine receptor in rat
      cerebral cortex.
AB  - Localization of nicotinic acetylcholine receptor (nAChR) alpha 4 subunits was
      investigated in rat cerebral cortex using a monoclonal antibody against alpha 4
      subunits. The antibody depleted more than 70% of the [3H]methylcarbamylcholine
      choline binding activity of the solubilized membrane fraction. By light
      microscopy alpha 4-like immunoreactivity (alpha 4-LI) was found through layers II
      to VI. The immunostaining was the most prominent in cell bodies and apical
      dendrites of pyramidal cells in layer V. By electron microscopy most
      immunoreaction products were observed in the rough endoplasmic reticulum,
      cytoplasmic matrix and synaptic membranes. Alpha 4-LI was detected in the
      postsynaptic membranes of neuronal cell bodies and apical dendrites. These
      findings suggest that alpha 4-containing subtypes serve as one possibly the
      postsynaptic nAChR in rat cerebral cortex.

PMID- 7500845
TI  - Muller and retinal pigment epithelial (RPE) cell expression of NGFI-A and c-fos
      mRNA in response to medium conditioned by the RPE.
AB  - Retinal pigment epithelial (RPE) cells secrete a factor(s) which promotes Muller
      and RPE cell survival and proliferation in vitro. These influences may play
      developmental and functional roles as well as contribute to ocular pathologies
      such as proliferative vitreoretinopathy (PVR). In the past few years, a number of
      immediate early genes (IEGs) have been identified. Many IBGs encode transcription
      factors, the expression of which is altered by stimuli such as growth factors.
      Since an RPE-derived factor(s) elicits proliferation of Muller and RPE cells, we
      investigated the expression of two IEGs, NGFI-A and c-fos, in both cell types
      after treatment with medium conditioned by the RPE (RPE-CM). We found that Muller
      and RPE cells had increased levels of NGFI-A mRNA following treatment with RPE
      CM; in contrast, only a slight increase in c-fos mRNA was induced in RPE, but not
      Muller cells. Immunolabeling for NGFI-A protein revealed nuclear staining in both
      cell types which corresponded with the increased mRNA levels in RPE-CM-treated
      cultures. This in vitro study demonstrates a potential mechanism by which RPE
      secreted factors may exert autocrine or paracrine effects on retinal cells in
      vivo. Specifically, NGFI-A may be the primary target of a second messenger system
      that is regulated by an RPE-derived factor(s).

PMID- 7500846
TI  - GAP-43 mRNA suppression by the ribozyme in PC12 cells and inhibition of evoked
      dopamine release.
AB  - We constructed a ribozyme designed to cleave the GAP-43 mRNA and which contained
      a bacteriophage T7 transcription terminator at its 3' site to maintain stability.
      The ribozyme was overexpressed in PC12 cells by pEF-BOS, a powerful mammalian
      expression vector. Consequently, PC12 cells overexpressing the GAP-43 ribozyme
      revealed a drastic decrease in the levels of GAP-43 mRNA expression, and the
      evoked dopamine release was significantly suppressed in these cell lines. These
      results support the previous observations that GAP-43 is associated with Ca
      dependent dopamine release in PC12 cells, and the ribozyme expression system used
      in the present study was demonstrated to be useful for suppression of the
      functions of specific mRNAs and exploration of specific gene products.

PMID- 7500847
TI  - Expression of alternate forms of brain opioid 'orphan' receptor mRNA in activated
      human peripheral blood lymphocytes and lymphocytic cell lines.
AB  - We screened a PHA (phytohemagglutinin)-activated human lymphocyte cDNA library
      for clones with homology to the recently cloned brain opioid receptors. A cDNA
      clone, AT7-5EU, was isolated which encodes the opioid 'orphan' receptor, a
      molecule with very high homology to the opioid receptor gene family, but which
      has not been shown to bind opioids or any other known compounds. The protein
      coding region of AT7-5EU has complete homology with a reported opioid 'orphan'
      clone isolated from human brain, but the 5' untranslated regions of AT7-5EU and
      the human brain clones are divergent, suggesting mechanisms for tissue-specific
      expression of this receptor. Northern analysis of AT7-5EU mRNA demonstrates the
      expression of this message in human lymphocytic cell lines of both B-and T-cell
      lineages. Furthermore, analysis of mRNA from human peripheral blood lymphocytes
      demonstrates that activation of the lymphocytes with PHA results in at least a 10
      fold induction of the AT7-5EU message. These results suggest that the opioid
      'orphan' receptor may have an important immunological function in addition to its
      function in the nervous system.

PMID- 7500848
TI  - Chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor
      mRNA and binding sites in various regions of the rat hippocampus.
AB  - Groups of rats were treated with buspirone (1 mg/kg/day) for 21 days using
      osmotic minipumps implanted subcutaneously. After buspirone treatment, the 5-HT1A
      receptor mRNA levels were significantly decreased in the CA1 and CA2 of the
      hippocampus, but were markedly increased in the dentate gyrus (DG), CA3 and CA4.
      The level of the 5-HT1A receptor binding sites was not significantly changed in
      these subhippocampal areas. Buspirone treatment markedly increased 5-HT2A
      receptor mRNA levels in the DG, CA2, CA3 and CA4. This was accompanied by a
      significant increase in the level of 5-HT2A receptor binding sites in all
      subhippocampal regions. These results demonstrate that chronic buspirone
      treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA as well as
      their expressed binding sites in various regions of the hippocampus.

PMID- 7500849
TI  - GDNF: existence of a second transcript in the brain.
AB  - The detection of the glial cell-line derived neurotrophic factor (GDNF) mRNA by
      RT-PCR in dissociated cell culture of rat embryonic or post-natal brain allowed
      the amplification of a doublet. The major band corresponded to the expected size
      and the minor one to a shorter product. We cloned and sequenced the latter
      product, and thus identified a mRNA potentially encoding for an isoform of the
      initially described precursor protein involved in GDNF synthesis.

PMID- 7500850
TI  - Repetitive strain injury (RSI) or cumulative trauma disorder (CTD) as legal and
      clinical entities. The need for a total reappraisal of this concept as being
      occupationally caused and therefore compensatable.

PMID- 7500852
TI  - Degrees of violence and blood spattering associated with manual and ligature
      strangulation: a retrospective study.

PMID- 7500851
TI  - Post traumatic stress disorder: turning the tide without opening the floodgates.
AB  - The development of the legal concept of nervous shock represents a compromise
      between the need to compensate those suffering psychiatric damage and the need to
      protect a defendant from unlimited liability. The criteria which have developed
      to achieve this balance are arbitrary ones, which take little account of
      psychological or physiological knowledge about post traumatic stress disorder. It
      is suggested that recent developments in scientific understanding of this
      condition could usefully inform the legal process, and that some aspects of the
      dilemma could be avoided.

PMID- 7500853
TI  - Male rape: the impact of a legal definition on the clinical area.
AB  - Recently the awareness of the issues surrounding male rape has received increased
      attention by both mental health workers and the general public following the
      introduction of the Sexual Offences Act 1994, and the recent case at the Old
      Bailey where a historical breakthrough was made in June 1995 following the first
      conviction for male rape under the new law. However, most of this attention has
      not resulted in many clinical breakthroughs in helping male rape survivors
      overcome the post-assault impact. Little is known about the prevalence, types of
      assault, consequences facing survivors and therapeutic options. Some evidence is
      being reported that male rape survivors develop Post Traumatic Stress Disorder
      following the assault. It has long been recognized that this is the case with
      female rape survivors, but to date there have been no significant UK prevalence
      studies which have examined this relationship. This paper discusses some of the
      issues surrounding male rape by focusing on the possible effects of the recent
      legal change on the clinical area.

PMID- 7500854
TI  - What price the concept of psychopathic disorder?
AB  - The current concept of psychopathic disorder is reviewed against a short
      historical background. Aetiology is commented upon briefly and key
      characteristics described. Support is provided for the view that the concept has
      a degree of usefulness in clinical management provided it is viewed in a focused
      and restricted fashion.

PMID- 7500855
TI  - Suicide and homicide in Costa Rica.
AB  - Suicide and homicide rates are lower in Costa Rica than in the United States.
      Firearms are used less often for suicide and for murder in Costa Rica than in the
      United States; hanging is more common as a method for suicide in Costa Rica and
      cutting/piercing more common as a method for murder. Suicide rates do not
      increase with age in Costa Rica, while the chances of being murdered do increase
      with age, unlike the United States.

PMID- 7500856
TI  - The coroner's system and under-reporting of suicide.
AB  - This study investigates the under-reporting of suicide with particular reference
      to differences between sex and age groups and the various modes of suicide. The
      study was performed retrospectively using the files of H M Coroner for South
      Yorkshire (West) over the years 1985 to 1991. There were 536 deaths judged on the
      balance of probability to be suicidal in nature. Only 60 per cent of these deaths
      received a suicide verdict and would therefore register in official suicide
      statistics. A significantly smaller proportion of females (51.7 per cent)
      received a suicide verdict than males (64.5 per cent). Of the young females (<
      45) 61.7 per cent were given a suicide verdict compared to 46.6 per cent of older
      females (45+). These differences are explained by different preferences for mode
      of suicide, in particular for poisoning using solids or liquids. Only 40 per cent
      of cases within this category received a suicide verdict. Drowning showed an even
      smaller percentage (24 per cent). Self-immolation (42 per cent) and jumping from
      a height (51 per cent) were also under-represented. Of these, self-poisoning,
      drowning and jumping from a height were relatively popular among females. In
      contrast, common causes of death favoured predominantly by males--hanging and
      carbon monoxide poisoning--received a high percentage of suicide verdicts (81 per
      cent and 90 per cent). Thus official suicide statistics produce a distorted view
      of the suicide population with relative under-reporting of females, particularly
      older females, and marked under-reporting of some causes of death, notably
      poisoning using solids or liquids, drowning, self-immolation and jumping from a
      height.

PMID- 7500857
TI  - Automatism re-visited: post-traumatic automatism as a defence to a serious
      criminal charge.
AB  - A case is described of a policeman who assaulted the man he was arresting after
      receiving a concussive blow to the head. The defence argued he was suffering from
      post-traumatic automatism and after juries were unable to agree a verdict in two
      trials he was acquitted. Aspects of post-traumatic automatism in English law are
      described and theories of the neurology of concussion and aggressive behaviour
      are discussed. Guidelines are proposed for the evaluation of cases of post
      traumatic automatism.

PMID- 7500859
TI  - Male Afro-Caribbean patients admitted to Rampton Hospital between 1977 and 1986-
      a control study.
AB  - All Afro-Caribbean patients admitted to the Mental Illness Division of Rampton
      Hospital (a Special Hospital) between 1977 and 1986 and a randomly selected
      control cohort of Non Afro-Caribbean patients admitted in the same period, were
      compared on a variety of sociodemographic, psychiatric, criminological, treatment
      and outcome variables. Significantly, fewer of the Afro-Caribbean patients
      attracted the legal classification of Psychopathic Disorder. Detailed analysis
      was thus restricted to mentally ill patients in the two ethnic groupings.
      Similarities outweighed differences. There was no difference between the groups
      in terms of index offence, previous custodial sentence, in-patient psychiatric
      admission (including previous Special Hospital admission), admission source,
      Mental Health Act section, length of admission (including readmission) to Special
      Hospitals, likelihood of discharge or place to which discharged. Medication
      history in Special Hospitals was similar at one year and three years after
      admission. Afro-Caribbean patients had a lower incidence of childhood
      institutional care, a decreased likelihood of a previous supervision order, an
      increased likelihood of a previous Court appearance and received higher doses of
      antipsychotic medication four weeks after admission to Special Hospital.

PMID- 7500858
TI  - Violence in clinical forensic medicine.
AB  - OBJECTIVE: to investigate the levels of physical and verbal violence experienced
      in the preceding year by doctors working in clinical forensic medicine. DESIGN
      AND SUBJECTS: anonymised questionnaire sent to all full members of the
      Association of Police Surgeons. RESULTS: 517 eligible questionnaires were
      returned; 18.2 per cent of respondents had experienced physical violence, a total
      of 150 incidents. Of those incidents 'warning signs' of violence had been present
      in only 25 per cent. A total of 54 working days were lost. Injuries included a
      fractured wrist and corneal scarring. Of the respondents, 65.5 per cent had
      experienced verbal violence (of which the most common type was obscenity); 11.8
      per cent had received training in dealing with verbal violence and 10.4 per cent
      in dealing with physical violence; 88 per cent believed that training on how to
      deal with violence should be part of police surgeon/forensic medicine training.
      CONCLUSION: verbal and physical violence are common in clinical forensic
      medicine. Training in dealing with these issues should be introduced.

PMID- 7500860
TI  - A review of diagnostic inaccuracy.
AB  - A review is presented of autopsy evidence demonstrating clinical diagnostic
      inaccuracy. Startling results emerge: the major clinical diagnosis is not
      confirmed in up to 45 per cent of cases, with typical error rates of up to 30 per
      cent; autopsy reveals unexpected major findings in up to 33 per cent of cases;
      management should have been different in up to 24 per cent of cases; clinicians
      cannot identify which patients are likely to have errant diagnoses; clinically
      'certain' diagnoses still have a high error rate. These error rates have not
      changed significantly since an early study in 1912 despite the current widespread
      use of advanced investigation modalities.

PMID- 7500861
TI  - Factitious post traumatic stress disorder: a case report.
AB  - A 24-year-old man presented with a convincing history of Post Traumatic Stress
      Disorder (PTSD). He claimed to be the victim of a widely publicized 'human bomb'
      attack by the IRA in Northern Ireland when he was serving with the armed forces.
      Psychometric tests for PTSD confirmed his symptoms. A subsequent check of public
      and military records demonstrated that he was a serviceman at that time, but
      showed conclusively that he could not have been present at the terrorist
      incident.

PMID- 7500862
TI  - Sudden infant death syndrome and lipoma: the presence of fat tissue in the spinal
      canal.
AB  - An epidural lipoma in the spinal canal in a case of Sudden Infant Death Syndrome
      (SIDS) is described. Histologic sections from ten SIDS cases were compared with
      five controls. It is concluded that there are no indications that an increased
      amount of fat in the spinal canal plays a role in the pathogenesis of SIDS.

PMID- 7500863
TI  - Sudden death caused by testicular germ cell tumour.
AB  - Most cases of sudden unexpected 'natural' death are due to primary disorders of
      the cardiovascular, respiratory and central nervous system. Sudden death due to a
      previously undiagnosed malignancy is rare in young, apparently healthy subjects.
      We report an unusual cause of sudden unexpected death due to pulmonary tumour
      embolism complicating an undiagnosed germ cell tumour of the testis in a 37-year
      old white male. Although death due to testicular tumours is not uncommon in young
      adult males, it rarely follows pulmonary embolism secondary to inferior vena cava
      (IVC) tumour invasion. A review of the literature revealed four other cases with
      a similar mechanism of death.

PMID- 7500865
TI  - Quantification of relative cerebral blood flow change by flow-sensitive
      alternating inversion recovery (FAIR) technique: application to functional
      mapping.
AB  - Relative cerebral blood flow changes can be measured by a novel simple blood flow
      measurement technique with endogenous water protons as a tracer based on flow
      sensitive alternating inversion recovery (FAIR). Two inversion recovery (IR)
      images are acquired by interleaving slice-selective inversion and nonselective
      inversion. During the inversion delay time after slice-selective inversion, fully
      magnetized blood spins move into the imaging slice and exchange with tissue
      water. The signal enhancement (FAIR image) measured by the signal difference
      between two images is directly related to blood flow. For functional MR imaging
      studies, two IR images are alternatively and repeatedly acquired during control
      and task periods. Relative signal changes in the FAIR images during the task
      periods represent the relative regional cerebral blood flow changes. The FAIR
      technique has been successfully applied to functional brain mapping studies in
      humans during finger opposition movements. The technique is capable of generating
      microvascular-based functional maps.

PMID- 7500864
TI  - Advances in physiological chemistry by in vivo NMR. A workshop sponsored by the
      Society of Magnetic Resonance held in Woods Hole, Massachusetts.

PMID- 7500866
TI  - Mapping the biodistribution and catabolism of 5-fluorouracil in tumor-bearing
      rats by chemical-shift selective 19F MR imaging.
AB  - A chemical-shift selective (CHESS) 19F MR imaging technique was used to map
      selectively the antineoplastic drug 5-fluorouracil (5-FU) and its major
      catabolite alpha-fluoro-beta-alanine (FBAL) in tumor-bearing rats. The pulse
      sequence employed a CHESS RF saturation pulse to suppress either the 5-FU or the
      FBAL resonance before the other component in the two-line 19F MR spectra was
      measured. Selective 5-FU and FBAL images with a spatial resolution of 10 x 10 x
      15 mm3 (1.5 ml) were obtained in 40 min from six ACl rats with implanted Morris
      hepatoma. Because the transmitter frequency could always be set to the Larmor
      frequency of the 19F resonance employed for imaging, the images were free of
      chemical-shift artifacts in readout and slice-selection direction. Whereas FBAL
      appeared only in the liver, the kidneys, and the bladder, 5-FU could also be
      detected in all major organs and in the muscular system. In the Morris hepatomas,
      a small 5-FU uptake and no FBAL accumulation were measured. The CHESS 19F MRI
      technique provides useful physiological and biochemical data on the
      biodistribution of the antineoplastic drug 5-FU and on the different catabolic
      activities of the tissues.

PMID- 7500867
TI  - High contrast and fast three-dimensional magnetic resonance imaging at high
      fields.
AB  - A new three-dimensional imaging strategy based on magnetization prepared
      ultrafast gradient recalled echo technique that demonstrates pronounced T1
      contrast at high fields is introduced. High-resolution three-dimensional image
      sets of human brain showing high contrast between white and gray matter areas are
      presented. The ratio of contrast-to-noise was examined as a function of the
      relevant parameters in the imaging sequence; calculations based on high-field T1
      values as well as the experimental data demonstrated that maximal contrast-to
      noise ratio is attained under the same magnetization preparation conditions both
      for cortical and subcortical gray matter relative to white matter, leading to
      approximately equivalent appearance of all gray matter areas in the same image.
      In addition, the images displayed clear visualization of subtle anatomical
      structures such as the subthalamic nuclei (ventral tier nuclei, dorsomedial
      nucleus, and pulvinar) and mammillothalamic tracts.

PMID- 7500868
TI  - In vivo localized proton NMR spectroscopy of thiamine-deficient rat brain.
AB  - Thiamine deficiency (TD) in rats produces lesions similar to those found in
      humans suffering from Wernicke's encephalopathy, an organic mental disorder
      associated with alcoholism. Male Sprague-Dawley rats (n = 29) were deprived of
      thiamine via a regimen of thiamine-deficient chow and daily intraperitoneal
      injections of the thiamine antagonist pyrithiamine hydrobromide. Spectra were
      obtained by using the STEAM sequence. No significant change occurred in the ratio
      of Cr/NAA, while the ratio of Cho/NAA declined significantly (60 +/- 11%) on Day
      14. Eleven rats received intraperitoneal injections of thiamine hydrochloride at
      the end of 12 days, and dose-dependent recovery in Cho/NAA was observed.

PMID- 7500869
TI  - Magnetization transfer in cartilage and its constituent macromolecules.
AB  - The goal of this work was to investigate magnetization transfer (MT) in cartilage
      by measuring water proton signals Ms/Mo, as an indicator of MT, in (i) single
      component systems of the tissue's constituent macromolecules and (ii) intact
      cartilage under control conditions and after two pathomimetic interventions.
      Ms/Mo was quantified with a 12-microT saturation pulse applied 6 kHz off
      resonance. Both glycosaminoglycans (GAG) and collagen exhibited concentration
      dependent effects on Ms/Mo, being approximately linear for GAG solutions (Ms/Mo =
      -0.0137[% GAG] + 1.02) and exponential for collagen suspensions (Ms/Mo = 0.80 x
      exp[-(%collagen)/6.66] + 0.20); the direct saturation of water could not account
      for the measured Ms/Mo. Although the effect of collagen on Ms/Mo is much stronger
      than for a corresponding concentration of GAG, Ms/Mo is not very sensitive to
      changes in collagen concentration in the physiological range. Tissue degradation
      with 25 mg/ml trypsin led to an increase in Ms/Mo from the baseline value of 0.2
      (final/initial values = 1.15 +/- 0.13, n = 11, P < 0.001). In contrast, a 10-day
      treatment of cartilage with 100 ng/ml of interleukin-1 beta (IL-1 beta) caused a
      19% decrease in Ms/Mo (final/initial values = 0.81 +/- 0.08, n = 3, P = 0.085).
      The changes in hydration and macromolecular content for the two treatments were
      comparable, suggesting that Ms/Mo is sensitive to macromolecular structure as
      well as concentration. In conclusion, whereas the baseline Ms/Mo value in
      cartilage may be primarily due to the tissue collagen concentration, changes in
      Ms/Mo may be due to physiological or pathophysiological changes in GAG
      concentration and tissue structure, and the measured Ms/Mo may differentiate
      between various pathomimetic degradative procedures.

PMID- 7500870
TI  - Vascular transit times in calcarine cortex: kinetic analysis of R2* changes
      observed using localized 1H spectroscopy.
AB  - A kinetic analysis of water signal intensity changes measured in human visual
      cortex by PRESS localized 1H spectroscopy at 500 ms resolution with light
      emitting diode (LED) goggle stimulation was used to determine vascular transit
      times for transitions between rest and activation. Monoexponential curve fitting
      was used to determine both R2* values for each free induction decay and the time
      constants for R2* changes with activation and deactivation. Measured transit time
      values were in general agreement with the literature, and were significantly
      shorter for "Off-->On" than for "On-->Off" transitions, consistent with known
      alterations in blood flow with activation and deactivation. The differences in
      transit times between "Off-->On" and "On-->Off" also varied with stimulus
      frequency in accordance with known physiology. This type of analysis may provide
      a useful means of analyzing functional activation data and for quantitatively
      comparing functional activation results from differing subjects and imaging
      sessions.

PMID- 7500871
TI  - On the use of two-dimensional-J NMR measurements for in vivo proton MRS:
      measurement of homonuclear decoupled spectra without the need for short echo
      times.
AB  - The potential of two-dimensional (2D)-J NMR for in vivo proton MRS is examined.
      Single voxel measurements on the rat brain were performed at 4.7 T using point
      resolved spectrocopy localization with a voxel size of 64 microliter and total
      measuring times of 10-15 min. It is shown that a series of measurements with only
      16 or fewer different echo times (TE) enables good signal localization in the f1
      axis corresponding to the coupling patterns. For data evaluation, the 2D-J NMR
      spectrum as well as cross-sections at given f1 values and projections onto the f2
      axis are used. A comparison between cross-section spectra taken at different f1
      values may help to solve problems of peak assignment. The projection of the 2D
      magnitude spectrum onto the f2 axis corresponds to a homonuclear decoupled 1D
      proton spectrum. Because the T2 relaxation times of several coupled resonances
      (e.g., myo-inositol and glutamate) are rather long, only minor losses in the
      quality of the projection spectra occur if the measurements with short TE (< or =
      50 ms) are not used for data processing. Thus, homonuclear decoupled proton
      spectra detecting uncoupled and several coupled resonances can be measured with
      high quality in vivo, even on MR systems that are not equipped with actively
      shielded gradients, prohibiting data acquisition with TEs of 50 ms or less.

PMID- 7500872
TI  - Pharmacokinetics of the 13C labeled anticancer agent temozolomide detected in
      vivo by selective cross-polarization transfer.
AB  - The anticancer agent temozolomide labeled with 13C (8-Carbamoyl-3-13C
      methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4-(3H)-o ne), was noninvasively detected
      in subcutaneous RIF-1 tumors by a selective cross polarization 13C NMR method, at
      a field strength of 9.4T. Pharmacokinetics of the drug, at a dose of 150 mg/kg,
      were determined for intravenous and intraperitoneal models of administration
      (three animals per mode). The half-life of the drug in the tumors was
      approximately 60 min. The uptake and clearance of the drug, however, varied
      significantly between individual hosts, for both modes of administration. These
      results demonstrate the feasibility of obtaining pharmacokinetics of anticancer
      agents for individual tumors without the need for a label that might modify drug
      activity (e.g., fluorine). The variability of the in vivo measurements, even
      within the same tumor model, demonstrates the necessity of directly monitoring
      the tumor to evaluate drug pharmacokinetics.

PMID- 7500873
TI  - Correlation of rapid changes in the average water diffusion constant and the
      concentrations of lactate and ATP breakdown products during global ischemia in
      cat brain.
AB  - Rapid changes in the average water diffusion constant, Dav = 1/3[Dxx+Dyy+Dzz],
      and in the concentrations of lactate and purine nucleotides and nucleosides were
      measured upon global ischemia (cardiac arrest) in cat brain, at a combined time
      resolution of 36 s (n = 7). At this time resolution, the normalized time curves
      of 1 - Dav and the increase in ATP breakdown product did not coincide, with the
      changes in Dav being most rapid. The normalized curves of 1 - Dav and the lactate
      increase coincided for the first 2-2.5 min after which the change in Dav was more
      rapid. After this time point, an excellent correlation was found between the drop
      in Dav and the decrease in energy utilization rate, which was calculated from the
      measured time curves of lactate formation and ATP breakdown, and from the time
      curve for phosphocreatine use reported in the literature. These results are in
      agreement with the expected biphasic changes in ion and water homeostasis during
      ischemia and with the model of diffusional changes being a consequence of a water
      shift from interstitial to intracellular space.

PMID- 7500874
TI  - 1H NMR determination of lactate 13C-enrichment in skeletal muscle: using a double
      quantum filter for the simultaneous editing of 13C-coupled and 13C-uncoupled
      methyl protons resonance.
AB  - 1H NMR simultaneous editing of 13C-coupled and 13C-uncoupled methyl protons
      resonance, using the selection of double quantum coherences by a gradient pulse,
      was analyzed in vitro and demonstrated in situ on the hindlimb of an exercised
      rat model postmortem. In vitro calibration showed agreement with theoretical
      analysis. High-resolution NMR of muscle extract confirmed the accuracy of the
      lactate 13C-enrichment calculated using the in situ NMR data and the calibration
      factor obtained in vitro.

PMID- 7500875
TI  - Noninvasive MRI thermometry with the proton resonance frequency method: study of
      susceptibility effects.
AB  - The temperature dependence of proton resonance frequency (PRF) is related to the
      temperature dependence of the screening constant and of the volume susceptibility
      constant. To evaluate the relative importance, an experimental setup was designed
      allowing quantification of both effects in different tissues, notably pure water
      in a gel structure, and porcine muscle and fat tissue. The temperature varied
      from 28 to 44 degrees C, a range significant for hyperthermia applications. Good
      agreement with results from the literature was obtained for water. Porcine muscle
      tissue behaves like water. Its screening constant varies linearly at a rate of
      0.97 10(-8) (degree C)-1 and the effects of temperature-induced changes of the
      susceptibility constant are negligible for muscle thermometry applications. The
      PRF-temperature relation in fat tissue, however, is almost completely determined
      by susceptibility effects.

PMID- 7500877
TI  - Measurement of fluid-shear rate by Fourier-encoded velocity imaging.
AB  - A new technique for estimating the blood fluid shear rate at the vessel wall is
      presented. The technique uses Fourier-encoded velocity imaging to determine the
      velocity distribution within a spatial element (voxel) that straddles the blood
      vessel wall interface. By appropriate processing, the velocity distribution (1)
      can determine the location of the wall-blood interface within the voxel and (2)
      estimate the velocity profile across the spatial extent of the voxel. From this
      information, accurate estimates of fluid shear rate may be obtained. Simulations
      are presented to illustrate this technique and to show the effects of various
      error sources, including differences in proton densities between blood and wall
      tissues and flow-related signal changes. Experimental evidence obtained for
      steady flow in straight tubes is also presented in support of the technique. The
      mean error in the experimental shear rate estimates found using the proposed
      technique was -15%. This represents a significant improvement over estimates
      obtained by extrapolation of the velocity profile over multiple voxels (mean
      error of -73%).

PMID- 7500876
TI  - Correlation of early reduction in the apparent diffusion coefficient of water
      with blood flow reduction during middle cerebral artery occlusion in rats.
AB  - To determine the relationship between reductions in the apparent diffusion
      coefficient of water (ADC) and in cerebral blood flow (CBF) during focal
      ischemia, we used diffusion-weighted magnetic resonance (D-MR) imaging and
      autoradiographic CBF analysis to examine rats subjected to 30 or 90 min of
      permanent middle cerebral artery (MCA) occlusion. In the 30-min occlusion group
      (n = 10), the area with substantially reduced ADC (15% or more below the
      contralateral level [ADC15]) corresponded best to the area with CBF below 25
      ml/100 g/min and was significantly smaller than the area with CBF below 50 ml/100
      g/min (CBF50), a level associated with reduced protein synthesis and delayed
      necrosis (40 +/- 13% versus 74 +/- 8% of the ischemic hemisphere; P < 0.0001). In
      the 90-min occlusion group (n = 6), the ADC15 area corresponded best to the CBF30
      to CBF35 area and was again significantly smaller than the CBF50 area (54 +/- 13%
      versus 73 +/- 20%, P < 0.05). Thus, the area of substantially reduced ADC at 30
      and 90 min represents only 53% and 74%, respectively, of the tissue at risk for
      infarction. These findings indicate a potential limitation in using early D-MR
      imaging to predict stroke outcome.

PMID- 7500878
TI  - Magnetic resonance fluoroscopy using spirals with variable sampling densities.
AB  - The imaging of dynamic processes in the body is of considerable interest in
      interventional examinations as well as kinematic studies, and spiral imaging is a
      fast magnetic resonance imaging technique ideally suited for such fluoroscopic
      applications. In this manuscript, magnetic resonance fluoroscopy pulse sequences
      in which interleaved spirals are used to continuously acquire data and
      reconstruct one movie frame for each repetition time interval are implemented.
      For many applications, not all of k-space needs to be updated each frame, and
      nonuniform k-space sampling can be used to exploit this rapid imaging strategy by
      allowing variable update rates for different spatial frequencies. Using the
      appropriate reconstruction algorithm, the temporal updating rate for each spatial
      frequency is effectively proportional to the corresponding k-space sampling
      density. Results from a motion phantom as well as in in vivo gadolinium
      diethylenetriaminopentaacetic acid (Gd-DTPA) bolus tracking studies in a rat
      model demonstrate the high temporal resolution achievable using these techniques
      as well as the tradeoffs available with nonuniform sampling densities. This paper
      focuses on the acquisition of real-time dynamic information, and all images
      presented are reconstructed retrospectively. The issues of real-time data
      reconstruction and display are not addressed.

PMID- 7500879
TI  - Myocardial tagging with B1 insensitive adiabatic DANTE inversion sequences.
AB  - A new technique, based on adiabatic delays alternating with mutations for
      tailored excitation (DANTE) inversion sequences, is presented for generating
      uniform contrast tags across the myocardial wall even in the presence of B1
      inhomogeneities. The utility of this pulse was demonstrated using a surface coil
      for both transmission and signal reception in phantom and animal heart tagging
      studies. The experimental data demonstrated uniform grid contrast over a sixfold
      variation of B1 magnitude, sharp tagging profiles, and the ability to follow the
      cardiac wall motion through the deformation of the fine rectangular tagging grid
      at different phases throughout the cardiac cycle.

PMID- 7500880
TI  - Regional comparison of tumor vascularity and permeability parameters measured by
      albumin-Gd-DTPA and Gd-DTPA.
AB  - Sequential albumin-Gd-DTPA and Gd-DTPA dynamic enhancement studies were performed
      in an animal tumor model for the comparison of regional vascularity and
      permeability parameters measured by these two different sizes of contrast agents.
      The early albumin-Gd-DTPA enhancement arises from the vascular compartment, and
      the averaged signal enhancement derived from the first 3 to first 6 images
      postinjection can be reliably used to assess vascularity. The signal intensity in
      the images during the period of 5-10 min post-albumin-Gd-DTPA injection shows a
      steady linear variation. The intercept of the linear relationship is another
      indicator of the vascularity and the slope represents the tumor permeability to
      albumin-Gd-DTPA. The Gd-DTPA enhancement study was analyzed by a two
      compartmental pharmacokinetic model to calculate the regional vascularity and
      permeability. The permeability parameters measured from albumin-Gd-DTPA and Gd
      DTPA show an excellent correlation. The vascularity parameters measured from
      albumin-Gd-DTPA show good linear correlation with the low vascularity groups
      measured by Gd-DTPA, but show saturation for the high vascularity groups. The
      enhancement mechanisms for both contrast agents are discussed to relate the
      imaging parameters to the physiological variables.

PMID- 7500881
TI  - The diminishing variance algorithm for real-time reduction of motion artifacts in
      MRI.
AB  - A technique has been developed whereby motion can be detected in real time during
      the acquisition of data. This enables the implementation of several algorithms to
      reduce or eliminate motion effects from an image as it is being acquired. One
      such algorithm previously described is the acceptance/rejection method. This
      paper deals with another real-time algorithm called the diminishing variance
      algorithm (DVA). With this method, a complete set of preliminary data is acquired
      along with information about the relative motion position of each frame of data.
      After all the preliminary data are acquired, the position information is used to
      determine which data frames are most corrupted by motion. Frames of data are then
      reacquired, starting with the most corrupted one. The position information is
      continually updated in an iterative process; therefore, each subsequent
      reacquisition is always done on the worst frame of data. The algorithm has been
      implemented on several different types of sequences. Preliminary in vivo studies
      indicate that motion artifacts are dramatically reduced.

PMID- 7500882
TI  - Dynamic Gd-DTPA enhanced MRI measurement of tissue cell volume fraction.
AB  - A new technique for measuring tissue cellular volume fraction, based on an
      improved modeling of the dynamic distribution of Gd-DTPA and the effect of proton
      exchange, is described. This technique uses peak T1 enhancement and blood Gd-DTPA
      concentration to compute tissue cellular volume fraction. The feasibility of this
      technique is demonstrated with computer simulations that explore the limits of
      the simplifying assumptions (small vascular space, slow vascular-extravascular
      proton exchange), and by direct comparison of MR and radionuclide cell fraction
      measurements made in muscle, liver, and tumor tissue in a rat model. The computer
      simulations demonstrate that with slow to intermediate vascular proton exchange
      and vascular fractions less than 10% the error in our cell fraction measurements
      typically remains less than 10%. Consistent with this prediction, a direct
      comparison between MR and radionuclide measurements of cell fraction demonstrates
      mean percent differences of less than 10%:1.9% in muscle (n = 4); 9% in liver (n
      = 1) and 9.5% in tumor (n = 4). Similarly, for all rats studied, the MR-measured
      cell fractions (muscle (0.92 +/- 0.04, n = 20); liver (0.76 +/- 0.11, n = 9);
      whole tumor (0.69 +/- 0.15, n = 22)) agree with the cell fraction values reported
      in the literature. In general, the authors' results demonstrate the feasibility
      of a simple method for measuring tissue cell fraction that is robust across a
      broad range of vascular volume, flow, and exchange conditions. Consequently, this
      method may prove to be an important means for evaluating the response of tumors
      to therapy.

PMID- 7500883
TI  - Phased array detectors and an automated intensity-correction algorithm for high
      resolution MR imaging of the human brain.
AB  - Two- and four-coil phased array detectors were developed to increase the
      sensitivity and resolution of MR imaging of the human brain cortex, especially
      for detecting cortical dysplasias in pediatric epilepsy patients. An automated
      intensity correction algorithm based on an edge-completed, low-pass filtered
      image was used to correct the image intensity for the inhomogenous reception
      profile of the coils. Seven phased array coils were constructed and tested. The
      sensitivity of these coils was up to 600% higher at the surface of the cortex
      than that achieved with a conventional head coil and up to 30% greater at the
      center of the head. The sensitivity obtained was comparable with that of a
      conventional small surface coil, but extended over the larger dimensions of the
      array and previously inaccessible areas such as the top of the head. The
      advantages of the improved sensitivity are demonstrated with high resolution
      images of the brain.

PMID- 7500884
TI  - Proton spectroscopic imaging of the human brain using phased array detectors.
AB  - Two and four-coil phased array detectors have been developed to increase the
      sensitivity of proton spectroscopic imaging of the human brain. These include a
      quadrature figure-8 coil for the study of the vertex, several arrays of 2-4 small
      overlapping (6-8 cm diameter) circular coils and a combination figure-8 coil plus
      circular coil. These were constructed in our laboratory and tested to assess
      their utility for brain spectroscopy. Methods for optimally combining the data
      from the independent receivers based on the analytical coil maps or measured
      signal to noise ratios (SNRs) of the data were investigated. High spatial
      resolution (0.2-0.4 cm3 voxel size) two- or three-dimensional chemical shift
      images of normal brain were obtained in 17-minute acquisitions. These spatial
      resolutions are comparable to those previously obtained with conventional small
      surface coils, but the specialized detectors allow this sensitivity to be
      achieved for a larger region or for previously inaccessible areas such as the top
      of the head. The coverage and SNR increases demonstrated are similar to those
      obtained in magnetic resonance phased array imaging.

PMID- 7500885
TI  - Compensation of multi-dimensional selective excitation pulses using measured k
      space trajectories.
AB  - Multidimensional spatially selective excitation pulses rely on the accuracy of
      gradient waveforms to achieve desired excitation volumes. Unfortunately, the high
      gradient slew-rates and magnitudes required by these pulses often lead to
      distortion of the waveforms produced by imaging systems resulting in poor
      selection profiles. In this paper, a k-space calibration procedure, used to
      determine the actual trajectory produced by the scanner's field gradients, is
      extended to two spatial dimensions. This measured information is then
      incorporated in a selective excitation design technique for correcting the RF
      pulse envelopes to compensate for gradient waveform induced distortion of the
      excitation volumes.

PMID- 7500886
TI  - Evaluation of protective effects of prostaglandin E1 on ischemic liver damage
      with in vivo 31P-MR spectroscopy.
AB  - The cytoprotective effect of prostaglandins (PG) was evaluated by in vivo 31P MR
      spectroscopy. Twenty rabbits were divided into two groups; the control group
      given physiological saline, and the PG group given prostaglandin E1 (0.5
      microgram/kg/min). Each solution was infused for 8 min, after which complete
      hepatic ischemia was induced for 20 min, followed by reperfusion for 40 min.
      During ischemia, beta-ATP decreased to 23.6% and 42.3%, phosphomonoester
      increased to 260% and 200% of their initial values in the control and the PG
      groups, respectively. Inorganic phosphate also increased. After reperfusion, beta
      ATP recovered to 65.2% and 96.5%, phosphomonoester to 130% and 110%, inorganic
      phosphate to 140% and 120% in the control and PG groups, respectively. The
      changes during ischemia were significantly smaller and the recoveries during
      reperfusion were more complete in the PG group. These results may confirm the
      cytoprotective effect of prostaglandins by in vivo 31P-MR spectroscopy.

PMID- 7500887
TI  - Optimization of T2-selective binomial pulses for magnetization transfer.
AB  - Accurate rules have been established to build binomial pulses up to fifth order,
      for selectively saturating protons at any given T2 with minimum power deposition.
      Pulse performance and sensitivity to experimental defects have been evaluated;
      the third order is generally found to be best suited. It is shown, by combining
      theory and experiment performed at 0.1 T, that matching the saturation pulse to
      T2 of the motionally restricted pool is essential to reveal exchange with free
      water protons. It is emphasized that, to date, lack of magnetization transfer
      contrast with binomial pulses is due mainly to insufficient RF level available
      with most MR imaging systems, especially at high magnetic field.

PMID- 7500888
TI  - Error in MR volumetric flow measurements due to ordered phase encoding in the
      presence of flow varying with respiration.
AB  - Respiratory ordered phase encoding is often employed in MRI studies to reduce
      image artifacts due to breathing motion. The purpose of this work was to evaluate
      error caused by the use of respiratory ordering of phase encoding in MR cine
      phase-contrast (CPC) volumetric flow measurements when the flow rate is sensitive
      to respiration. It was hypothesized that this effect is due to the systematic
      biasing of a respiratory-induced phase modulation function in k-space. A
      theoretical model for the effects of respiration was developed and then tested in
      flow phantom studies and in normal volunteer studies. In phantom experiments, the
      use of respiratory ordering induced an error of as much as 13% in CPC volumetric
      flow measurements. In preliminary volunteer studies, error was as high as 26% in
      superior vena cava flow measurements versus less than 1% error in the ascending
      aorta. It is concluded that a potential for error exists in CPC volumetric flow
      measurements obtained with the use of respiratory ordering schemes. Volunteer
      studies with larger numbers are warranted. Clinical applications in which this
      effect may be important include flow measurements in vessels subject to
      variations in flow due to respiration, such as the venae cavae, pulmonary
      vasculature, and portal vein.

PMID- 7500889
TI  - Correction of motional artifacts in diffusion-weighted images using a reference
      phase map.
AB  - A method of correcting motional artifacts in diffusion-weighted images is
      described. Motion causes changes in the phase of the k-space NMR signal and
      thereby introduces positional shifts (or ghosts) in the spatial domain. By
      correcting the phase of the NMR signal before Fourier transformation, the image
      sharpness is greatly enhanced. The new method measures the phases of the NMR
      signal once and stores this phase information in a phase map. Subsequent images
      with motional artifacts are corrected during postprocessing using this reference
      phase map.

PMID- 7500890
TI  - Calculation of signal intensities in hybrid sequences for fast NMR imaging.
AB  - A number of techniques that recently have been used for fast NMR-imaging are
      based on a hybrid sequence of echo planar imaging (EPI) and FLASH imaging: after
      each NMR excitation several k-space lines are measured. The complete k-space is
      covered by performance of several excitations. It has been observed that there is
      usually an optimal hybrid sequence that maximizes the signal-to-noise ratio. In
      this work, a method is presented that allows a determination of the optimal
      sequence as a function of the relaxation times T1 and T2*.

PMID- 7500891
TI  - Cine spiral imaging.
AB  - Interleaved spiral scanning of k-space is an efficient and fast method for
      imaging dynamic processes. In this article, a cine version of interleaved spiral
      imaging is presented. The method is shown to overcome the "lightning-flash"
      artifacts of the conventional triggered (gated) method. Compared with the
      segmented k-space 2DFT method, it achieves better temporal resolution in a
      comparable or shorter scan time. Preliminary human studies show that the method
      is a promising tool for imaging dynamic processes.

PMID- 7500892
TI  - Quiet transverse gradient coils: Lorentz force balanced designs using geometrical
      similitude.
AB  - The principle of active acoustic screening, recently introduced by Mansfield et
      al. (1) to reduce acoustic noise in gradient coils for MRI, is applied to the
      design of transverse distributed gradient coils of the fingerprint design. The
      results indicate that for complete Lorentz force balancing and for exact
      satisfaction of Kirchoff's law, it is necessary to have a coil system wound on
      four cylinders if full active magnetic screening of the assembly is required.

PMID- 7500894
TI  - Reviews in molecular medicine.

PMID- 7500893
TI  - MR imaging of regional cardiac function: low-pass filtering of wall thickness
      curves.
AB  - Wall thickness curves (WTCs) derived from MR images are subject to considerable
      measurement error. This study determines the effects of low-pass Fourier
      filtering of WTCs on functional parameters derived from the curve: peak rate of
      wall thinning (PRWT) and time to PRWT (TPRWT). The inter-subject standard
      deviation (SD) of PRWT changed from 0.35 to 0.18, and the SD of TPRWT from 34.3
      to 29.5. Differences between neighboring segments decreased from 0.31 to 0.15%
      mean thickness/ms for PRWT (P = 0.012), and from 35.0 to 19.0 ms for TPRWT (P =
      0.005). It is concluded that filtering of MR imaging-derived WTCs contributes to
      a better representation of myocardial wall motion.

PMID- 7500896
TI  - Epidemiologic aspects of infective endocarditis in an urban population. A 5-year
      prospective study.
AB  - A prospective study of the epidemiology of infective endocarditis (IE) in a well
      defined urban population of 428,000 inhabitants during a 5-year period was
      carried out. All patients were treated in the same institution, and history,
      diagnostic procedures, and treatment were standardized. Of 233 consecutive
      suspected episodes of IE, 127 fulfilled the modified von Reyn criteria. After
      patients not living in the defined area were excluded, 99 episodes in 90 patients
      were analyzed in the epidemiologic part of the study. Of these, 33 episodes were
      definite endocarditis, verified by surgery or autopsy; 35 probable; and 31
      possible endocarditis episodes. Another 34 episodes were found retrospectively
      and are included in the incidence calculation. The crude incidence was calculated
      to be 6.2/100,000 inhabitants per year, which is high compared to earlier
      studies. Adjusted to the population of Sweden, the incidence was 5.9/100,000
      inhabitants per year. The annual incidence was higher for women, 6.6/100,000,
      than for men, 5.8/100,000. In the oldest age-group (80-89 years) the annual
      incidence was 22/100,000 in the prospective study and 30/100,000 if retrospective
      cases were included. Contrary to almost all other studies, we did not find a male
      predominance among our cases. Only 7% of patients were intravenous drug abusers,
      and 15% had a prosthetic valve. The most common bacteria were methicillin
      susceptible Staphylococcus aureus (31%) and alpha-streptococci (28%); 12% of
      episodes were culture negative. The mortality from IE in the population was
      1.4/100,000 inhabitants per year. A higher-than-expected incidence of IE was
      found, especially among older patients and women.

PMID- 7500895
TI  - Gaucher disease.

PMID- 7500897
TI  - Nosocomial bacteremia due to Acinetobacter baumannii. Clinical features,
      epidemiology, and predictors of mortality.
AB  - To study the possible predisposing factors, clinical features, molecular
      epidemiology, and factors affecting mortality associated with bacteremia due to
      Acinetobacter baumannii, we reviewed 87 episodes of A. baumannii bacteremia
      occurring in 79 patients hospitalized at 2 university tertiary care centers and 4
      community-based hospitals during a recent 18-month period. Plasmid DNA analysis
      and analysis of genomic DNA with pulsed-field gel electrophoresis was performed
      to investigate possible epidemiologic relationship. All patients acquired their
      infections in the hospital, and no seasonal variation was observed. Among
      patients with A. baumannii bacteremia, 91% were hospitalized in an intensive care
      unit, 99% had indwelling vascular catheters, 81% received prior broad spectrum
      antimicrobial therapy, 70% were mechanically ventilated, and 47% had major
      surgical procedures. In 39 cases (45%) the infection was related to indwelling
      vascular access devices. Other infections included pneumonia (9%),
      tracheobronchitis (22%), meningitis (2%), and burn wound infections (4%). Septic
      shock occurred in 30% of patients. All isolates were multidrug resistant.
      Polymicrobial bacteremia was observed in 35% of cases. The crude mortality rate
      was 44%. Death was considered attributable to A. baumannii bacteremia in 15 (19%)
      patients. All patients with pneumonia as the primary site of infection died.
      Using multivariate analysis, we identified 3 independent predictors of mortality:
      the presence of a rapidly or ultimately fatal underlying disease (p = 0.0009),
      septic shock at the onset of bacteremia (p = 0.0013), and mechanical ventilation
      (p = 0.016). Epidemiologic typing revealed that 82 episodes were associated with
      different hospital outbreaks of infection, and only 7 episodes were due to
      epidemiologically unrelated strains.

PMID- 7500898
TI  - Atheroembolic renal failure after invasive procedures. Natural history based on
      52 histologically proven cases.
AB  - Atheromatous plaque material containing cholesterol crystals may dislodge and
      cause distal ischemia. To characterize atheroembolic renal failure, we
      retrospectively evaluated all patients at the Massachusetts General Hospital from
      1981 to 1990 with both renal failure and histologically proven atheroembolism
      after angiography or cardiovascular surgery. Over the 10-year period, 52 patients
      were identified. They tended to be elderly men with a history of hypertension
      (81%), coronary artery disease (73%), peripheral vascular disease (69%), and
      current smoking (50%). Within 30 days of their procedure, only 50% of patients
      had cutaneous signs of atheroembolism, and 14% had documented blood eosinophilia.
      Urinalysis was often abnormal. Hemodynamically unstable patients died shortly
      after their procedure, yet renal function in the remainder continued to decline
      over 3 to 8 weeks. Patients who received dialysis had a higher baseline serum
      creatinine than those who did not (168 +/- 44 mumol/L versus 133 +/- 18 mumol/L,
      p = 0.02), with dialysis starting a median of 29 days after the procedure.
      Patients with renal failure due to atheroembolism alone, as opposed to multiple
      renal insults, were more likely to recover renal function (24% versus 3%, p =
      0.03) and had a lower risk of death during the 6 months after their procedure
      (log-rank p = 0.002). Renal failure due to procedure-induced AE is characterized
      by a decline in renal function over 3 to 8 weeks. This time course is not
      consistent with most other iatrogenic causes of renal failure, such as
      radiocontrast or nephrotoxic medications, which present earlier and often resolve
      within 2 to 3 weeks after appropriate intervention.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7500900
TI  - [Atopy, asthma and the judgement of preemployment fitness].
AB  - The preemployment medical examination is a practice viewed as important by
      recently introduced Italian laws (D.L. 277/91 and 626/94), even if its efficacy
      with regard to atopy is frequently a matter of controversy. It has been assumed
      that atopy (with a prevalence in the general population around 30%) is a
      predictive discriminant in the prevention of occupational allergic asthma, but a
      review of the literature shows that the hypothetical exclusion of 23 per cent of
      total job applicants (because they are atypical) would seem to prevent only 55
      per cent of asthma cases. At the present time, the concept of discrimination in
      employment founded on presence of atopy is scientifically unsubstantiated and
      ethically unacceptable.

PMID- 7500899
TI  - [The diffusion of information on the carcinogenicity of asbestos in the Italian
      scientific community before 1965].
AB  - The spreading of information on asbestos carcinogenicity within the Italian
      scientific community before 1965. The paper deals with the development of
      recognition of asbestos carcinogenicity within the Italian scientific community.
      This development was difficult in Italy as in other countries. Articles and other
      papers in handbooks and congress proceedings, by Italian authors, published in
      the period 1934-1965, were considered. The first cases of lung cancer in Italian
      workers exposed to asbestos were observed in 1955-56, the first cases of
      malignant mesothelioma in 1965. The cases observed were very few, but knowledge
      on asbestos carcinogenicity became widespread within the Italian scientific
      community during the fifties (from 1953 on wards) with the publication of several
      handbooks of occupational medicine.

PMID- 7500901
TI  - [Economic and occupational activities at an increased risk of mortality for lung
      tumors in Turin (1981-89) and in Italy (1981-82)].
AB  - In the framework of occupational disease surveillance program, based on
      integration of current information systems, the first Italian occupational
      mortality study was carried out. This paper reports on excess lung cancer risk by
      industry and occupation. The study population consists of subjects included in
      the Italian Cross-Sectional Study (STI) and in the Turin Longitudinal Study
      (SLT), both of which are surveys based on record-linkage procedures between
      census records and death certificates. The STI is a six-month follow-up of
      Italian residents at the 1981 census. The SLT is a prospective study of Turin
      residents at the 1981 census, followed for mortality up to 1989. Only persons
      aged 18-64 years at entry, and economically active, were eligible for the
      occupational mortality analysis (i.e. 15,734 deceased individuals out of 13
      million subjects in the STI, and 435,608 individuals, among whom 10,789 deaths
      occurred, in the SLT). Information about job and economic activity recorded at
      census consisted of the Italian standard 1981 industry and occupation codes. Lung
      cancer relative risks by category of industry and job were estimated as mortality
      odds ratios (MOR) in the STI, and as observed to expected death ratios (SMR) in
      the SLT. Only excess risks based on > or = 3 observed cases and with p < 0.1,
      were included in the present report. Lung cancer mortality was increased in
      different industries and jobs. The excess risks found in the mechanic and
      transport industries are of particular interest in a public health perspective,
      due to the high number of Italian workers employed in these sectors. From an
      etiologic point of view, however, careful attention should be paid to the excess
      lung cancer risks among workers in the wood manufacturing industry, in meat
      preparation, and in nursing occupations, where detailed analytical studies of
      exposure profile and cancer risk are warranted.

PMID- 7500903
TI  - [Work-related accidents in minors in Lombardy].
AB  - Work-related injuries in children and adolescents represent a negative indication
      of more general inequities of the society in which events occur. Their
      characteristics are not well described, particularly in Italy, and this paper is
      aimed at highlighting some fundamental aspects of these injuries. The case in
      point is represented by the injuries that received compensation and occurred in
      the Lombardy Region (Italy) between 1984 and 1989 and involved people under the
      age of eighteen. The injuries occurring in the same period and area in workers
      over eighteen were used for comparison. Work related injuries in minors were more
      frequent in crafts activities than in industry, but their gravity (in terms of
      deaths or permanent consequences) was lower than in the corresponding adult
      workers. Ninety percent of the events in young workers occurred in males, in each
      age category, and about 5% of the cases pertains to very young workers (less than
      15 years). Cuts/lacerations are the most frequent type of lesion (49.9%) and the
      hands represent the site most frequently involved (55.5%). The great majority of
      the observed injuries pertains to a limited number of economic activity sectors:
      about 75% of the cases occurred in ten sectors. Metal manufacturing, construction
      and machine production scored first, with interesting correlations with the same
      sectors in adult workers. Ten specific occupations represent over fifty percent
      of the cases, with mechanics and bricklayers at the top. The description of the
      accident in terms of mode of occurrence and the agents involved was less
      informative and not specific.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500902
TI  - [The first case of severe pneumopathy due to hard metals successfully undergoing
      a lung transplant].
AB  - The paper describes a case of chronic interstitial lung disease due to exposure
      to hard metals, with progressive global respiratory insufficiency, treated with
      single lung transplant. Clinical conditions improved gradually after the
      operation and after more than two years the patient was in good health and had
      resumed an almost normal life and relationships.

PMID- 7500904
TI  - [The risk of the carpal tunnel syndrome in some work activities].
AB  - The aim of the study was to generate hypotheses on what could be the ISTAT
      (National Institute of Statistics) job classes with a major risk of carpal tunnel
      syndrome in order to plan more specific analytic epidemiology studies and apply
      more correct ergonomic solutions. A case-control cross-sectional survey without
      matching was carried out. The source of data were the computerized medical
      records of a large regional hospital: 833 carpal tunnel syndrome cases (mean age
      48, SD 9.33) and 3222 controls (mean age 43.5, SD 13.22) hospitalized for other
      diseases, were selected. The odds ratio (OR) and 95% confidence limits,
      controlled for age and gender by a logistic linear regression model, were
      calculated as measures of association for the comparison between non-exposed
      managerial/administrative staff and industrial workers. The analysis showed a
      statistically significant risk for some ISTAT job classes, in particular class 53
      (spinners, weavers, dyers and similar jobs) (OR = 2.65; C.L. 1.52-4.62) class 54
      (knitters, tailors, hatmakers, upholsterers and similar jobs) (OR = 1.69; C.L.
      1.06-2.71), 55 (tanners, shoemakers, leather manufacture workers and similar
      jobs) (OR = 2.74; C.L. 1.66-4.53) and group 742 (Hotel and restaurant cooks) (OR
      = 2.99; C.L. 1.45-6.13). Job classes 45 (carpenters, welders and similar jobs).
      62 (electricians, electrotechnicians, radio engineers and similar jobs), 63
      (gasfitters, plumbers, heating engineers and similar jobs) and 85 (porters and
      other jobs involving manual handling of loads) showed ORs higher than 2 but
      without statistical significance. The results are valid for planning further
      studies, especially in the textile and shoe and leather manufacturing sectors.

PMID- 7500905
TI  - [The application of D.Lgs. 626/94 in USL (local health unit) enterprises and
      hospital enterprises: a proposal for organizing preventive activities. The
      Associazione Italiana di Medicina Preventiva dei Lavoratori della Sanita].

PMID- 7500907
TI  - [A code of ethics for qualified physicians].

PMID- 7500906
TI  - [Nylon fiber and possible lung pathology].

PMID- 7500908
TI  - Riluzole for amyotrophic lateral sclerosis.

PMID- 7500909
TI  - Intravenous amiodarone.

PMID- 7500910
TI  - Dalteparin--another low-molecular-weight heparin.

PMID- 7500912
TI  - Intact antigen presentation for Epstein-Barr virus (EBV)-specific CTL by a
      lymphoblastoid cell line established from a patient with severe chronic active
      EBV infection.
AB  - Severe chronic active Epstein-Barr virus (EBV) infection is a lymphoproliferative
      disease characterized by extremely high antibody titers to EBV, fever,
      lymphadenopathy, hepatosplenomegaly, and pancytopenia, without any prior
      immunological abnormality. A spontaneous lymphoblastoid cell line was established
      from a 4-year-old boy with severe chronic active EBV infection.
      Immunofluorescence and Western blotting analyses showed that the cell line was of
      B cell origin and expressed Epstein-Barr nuclear antigens 1, 2 3a, 3b and 3c, and
      latent membrane protein 1, which are reported to be targets for EBV-specific
      cytotoxic T lymphocytes (CTL). The cytotoxicity of peripheral blood mononuclear
      cells derived from the patient and his HLA-identical sister was assayed against
      the cell line. The cell line was recognized and killed by anti-EBV CTL derived
      from the HLA-identical sister, but the patient's peripheral blood mononuclear
      cells had no cytotoxicity. We conclude that antigen presentation in the EBV
      infected cells from the patient is intact and sufficient for generation of an EBV
      specific CTL response. These observations suggest that severe chronic active EBV
      infection may not be caused by impaired EBV-antigen presentation of the infected
      cells but by impaired cellular immune responses to the virus. Our results also
      suggest the therapeutic possibility that this disease may be treated by adoptive
      transfer of EBV-specific CTL or bone marrow transplantation from an HLA-matched
      donor whose immune response to EBV is intact.

PMID- 7500913
TI  - Detection of specific human immunodeficiency virus IgM antibodies.
AB  - This study was done to demonstrate whether the use of the antigen-sandwich human
      immunodeficiency virus (HIV) antibody-screening assays (3rd generation assays),
      which detect all classes of anti-HIV immunoglobulins, leads to an earlier
      detection of HIV IgM compared to the 2nd generation HIV antibody-screening
      assays. We tested sequential bleeds of three donors obtained from commercially
      available seroconversion panels. Anti-HIV testing was done before and after high
      performance liquid chromatography separation of IgG and IgM fractions. The
      positive result of the first bleedings from all three panels was linked to the
      IgM fraction, while at that time the IgG fraction was still negative. For
      subsequent samples drawn 5-9 days later, a positive signal was obtained with the
      IgG fraction in addition to a stronger positive signal obtained with the IgM
      fraction. We conclude that an assay capable of simultaneously detecting different
      immunoglobulin classes, including IgM, will help to narrow the "window period"
      for serological detection of seroconversion to HIV by detecting anti-HIV IgM
      containing samples earlier than conventional assays using only anti-human IgG
      enzyme conjugates (indirect anti-HIV-screening assay, 2nd generation assays).

PMID- 7500911
TI  - The epidermolytic (exfoliative) toxins of Staphylococcus aureus.
AB  - Two epidermolytic toxins, produced by different strains of Staphylococcus aureus,
      split human skin at a site in the upper epidermis. Clinical effects are most
      common in infants, but adults are susceptible. Epidermolysis may also be observed
      in the mouse, in vivo and in vitro, and in a few other mammals. Recent in vitro
      experiments have demonstrated an inhibition by chelators and point to metal-ion,
      possibly Ca2+, involvement. The epidermolysis effect is insensitive to a wide
      range of other metabolic inhibitors. The toxin amino acid sequences are similar
      to that of staphylococcal proteinase, and new experiments by chemical
      modification and site-directed mutagenesis have shown that toxicity depends on
      'active serine' residues of a catalytic triad similar to that found in serine
      proteases. Furthermore the toxins possess esterolytic activity, also dependent on
      the 'active serine' sites. However, the toxins have low or undetectable activity
      towards a range of peptide or protein substrates. In histological and related
      studies, the toxins bound selectively to an intracellular skin protein,
      profilaggrin, but there was no evidence that the toxin can enter intact epidermal
      cells. Therefore, although the circumstantial evidence that the toxins act by
      proteolysis is convincing, a specific skin proteolytic substrate for the toxin
      has not been identified.

PMID- 7500914
TI  - Sequence analysis of ospA genes shows homogeneity within Borrelia burgdorferi
      sensu stricto and Borrelia afzelii strains but reveals major subgroups within the
      Borrelia garinii species.
AB  - The genes coding for the outer surface protein A (OspA) of 19 different Borrelia
      burgdorferi strains belonging to the seven OspA-serotypes 1-7, previously
      described [Wilske et al. (1993) J Clin Microbiol, 31: 340-350], have been
      investigated. B. burgdorferi sensu lato strains were chosen from various
      biological sources (ticks, human skin and cerebrospinal fluid) as well as
      different geographical origins (Germany, Slovenia, Austria, United States). The
      open reading frames of all ospA genes consist of 819-825 nucleotides
      corresponding to proteins of approximately 30 kDa. The ospA sequences obtained in
      this study and previous published studies were compared with the results from
      OspA serotyping with monoclonal antibodies. The classification into the seven
      OspA serotypes could be confirmed on a genetic basis (ospA genotypes 1-7) for all
      strains analyzed so far (n = 29). In addition, one strain without OspA expression
      could be assigned to ospA genotype 2. Genetic stability could be proven for the
      ospA gene of B. burgdorferi strain PWudI after inocculation and reisolation from
      a gerbil. However, we found evidence for intragenic recombination by cluster
      analysis of ospA sequence data. Accordance of ospA genotype 1 strains with B.
      burgdorferi sensu stricto and ospA genotype 2 strains with B. afzelii, as well as
      the ospA genotype strains 3-7 with B. garinii was confirmed by pulsed-field gel
      electrophoresis of MluI-digested genomic DNA. B. garinii is not only more
      heterogeneous in respect to the OspA-encoding genes, but shows moreover major
      subgroups formed by genotypes 4, 5 and 6 and genotypes 3 and 7,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500915
TI  - Expression of Staphylococcus saprophyticus surface properties is modulated by
      composition of the atmosphere.
AB  - Expression of two major surface proteins of Staphylococcus saprophyticus, the
      haemagglutinin and the Staphylococcus saprophyticus surface-associated protein
      (Ssp), required carefully defined culture conditions. The Ssp is produced when
      bacteria are grown on agar, whereas expression of the haemagglutinin requires
      growth in broth. We sought to identify the environmental signals that are
      responsible for this modulation. Varying the pH, the osmolarity of the growth
      medium or the temperature did not influence expression of the proteins. In
      contrast, growth in an anaerobic atmosphere increased haemagglutination titres
      and fibronectin binding (both mediated by the haemagglutinin) but suppressed
      production of the Ssp. As the influence of the CO2 level could be excluded, we
      conclude that expression of these surface proteins is probably modulated by the
      O2 content of the atmosphere.

PMID- 7500917
TI  - Cellular receptor structures for pseudorabies virus are blocked by antithrombin
      III.
AB  - Pseudorabies virus (PrV), an alphaherpesvirus of swine, uses cellular heparan
      sulfate residues as a receptor for attachment. Interaction of the virus with its
      receptor is mediated by the envelope glycoprotein C (PrV-gC), a protein with
      heparin-binding properties. We have previously shown that a region of this
      protein shows structural similarities to the high-affinity heparin-binding site
      of the serum protease-inhibitor antithrombin III (ATII). In this publication, we
      describe the effect of ATIII on interaction of PrV with its cellular receptor.
      ATIII bound specifically to heparan sulfate residues on the surface of
      herpesvirus-permissive RK13 cells. Binding of ATIII to RK13 cells interfered with
      adsorption of radioactively labelled PrV to these cells. Enzymatic treatment
      using heparinase I (E.C. 4.2.2.7) removed the receptor for PrV as well as the
      receptor for ATIII. Since amino acids 130-137 of the high affinity heparin
      binding site of ATIII show structural similarities to amino acids 134-141 of PrV
      gC, both sequences were synthesized as synthetic peptides. Although interaction
      of the peptide derived from ATIII with heparin was significantly stronger, both
      peptides interacted specifically with heparin in assays in vitro. These results
      suggest that PrV and ATIII interact with the same structure on the cellular
      surface.

PMID- 7500918
TI  - [Incidence of severe hypoglycemia in relation to metabolic control and patient
      knowledge].
AB  - BACKGROUND: The question whether the incidence of severe episodes of
      hypoglycaemia in type I and type II diabetics correlates with the level of the
      patient's knowledge about hypoglycaemia and the quality of metabolic control.
      PATIENTS AND METHODS: A total of 234 consecutive type I diabetics (age and
      diabetes duration 48 and 16 years, respectively; blood glucose, self-monitored
      63%) and 237 type II diabetics treated with glibenclamide (mean dose 6.7 mg/day)
      (age and diabetes duration 65 and 9 years, respectively; glucosuria, self
      monitored 36%) who attended the Berlin outpatient diabetic centre were
      investigated. RESULTS: Of the type I diabetics 23 (9.8%) experienced a total of
      32 severe episodes of hypoglycaemia (incidence 0.14 per patient/year). Patients
      at risk of experiencing hypoglycaemia were about 20 years younger, injected
      insulin more often (3.8 vs 2.3 injections/day; p < 0.01) and had a lower HbA1
      level (7.8% vs 9.0%; p < 0.01) than those having no hypoglycaemic reactions. Ten
      of the 23 diabetics suffering severe episodes of hypoglycaemia showed signs of
      kidney disease. The most common causes of hypoglycaemia were dietary errors
      (18.7%) or incorrect doses of insulin (12.5%), alcohol consumption (12.5%) and
      unusual physical exertion (23%). In terms of their knowledge about hypoglycaemia,
      there were no notably differences between patients with and those without
      hypoglycaemic reactions. Among the 237 type II diabetics treated with
      glibenclamide, three (1.3%) experienced one episode of severe hypoglycaemia each
      (incidence: 0.013 patient/year). Old age, maximum dosage of glibenclamide (15
      mg/day) and multimorbidity were characteristic of these patients. Enquiries
      showed that only 49% (n = 160) of all type II diabetes had adequate knowledge
      about hypoglycaemia. CONCLUSION: In type I diabetics, there appears to be no
      relationship between the hypoglycaemia risk and the patient's theoretical
      knowledge of hypoglycaemia. In future, apart from theoretical knowledge, more
      attention must be paid to practical training to improve awareness of
      hypoglycaemia. Educational programs for type II diabetics must attach more weight
      to the problem of hypoglycaemia.

PMID- 7500916
TI  - Sister chromatid exchange-inducing DNA lesions and depression of activation
      markers on the surface of cultured peripheral blood mononuclear cells after the
      addition of streptococcal pyrogenic exotoxins A and C.
AB  - Cultivation of peripheral blood mononuclear cells (PBMC) in the presence of
      streptococcal pyrogenic exotoxins (SPE) A and C resulted in a significant
      induction of sister chromatid exchange (SCE)-inducing DNA lesions. Concomitantly,
      the expression of interleukin-2 receptor alpha chain (IL-2R alpha chain),
      transferrin receptor (TfR), and major histocompatibility complex class II
      molecule HLA-DR on the surface of phytohemagglutinin-activated T cells from whole
      blood culture cells (WBCC) significantly decreased within 72 h, that is at least
      two cell cycles, whereas unstimulated T cells from WBCC did not express these
      markers but had lost their CD3 molecules, an effect reported to precede apoptosis
      as part of a T cell inactivation pathway. However, no apoptotic cells were
      observed within a cultivation period of 120 h. We observed clearcut differences
      in the responses towards SPE A in WBCC and isolated lymphocytes, since SPE A
      treated lymphocytes showed an increase in the [3H]thymidine incorporation and did
      express IL-2R alpha chain and TfR on their cell surface. Regardless of the
      precise underlying mechanism, T cells from WBCC seem to be in a state of
      functional incompetence. The data presented here are the first to provide strong
      evidence that streptococcal toxins produce SCE-inducing DNA lesions in PBMC, an
      effect that might contribute to the process of immune cell lethality in
      streptococcal toxic shock-like syndrome and could be of pivotal importance in the
      pathogenesis of severe streptococcal disease.

PMID- 7500919
TI  - [Measuring blood pressure at the wrist: critical analysis of a validation study].
AB  - BACKGROUND: The new device "Blood Pressure Watch" (BPW) by NAIS-Matsushita, which
      measures blood pressure oscillometrically at the hand wrist, is preferred by many
      hypertensive patients as a device for self-measurements because of its smallness
      and simple applicability. SUBJECTS AND METHOD: To evaluate the accuracy of blood
      pressure measurements with this device we determined the blood pressure four
      times consecutively in the aortic arch using a Statham P23 and the BPW
      simultaneously at the left hand wrist in 27 patients (58.6 +/- 10.3 [range: 36 to
      76] years; 21 male) after a coronary angiography. RESULTS: With a correlation
      coefficient of 0.85 for systolic and 0.84 for diastolic pressure mean blood
      pressure was determined higher (systolic: +1.4 +/- 10.1 mm Hg, diastolic: +4.4 +/
      7.6 mm Hg) by the BPW compared to the aortic arch pressure. While there was no
      correlation between systolic differences and patients' age, it could be
      demonstrated that with increasing age the BPW exhibited higher diastolic blood
      pressure values than those measured in the aortic arch. Multiple regression
      analysis revealed that this was due to inability of the BPW to detect low
      diastolic blood pressures (r = 0.89, p < 0.001). CONCLUSIONS: 1. For the majority
      of hypertensive patients the hand wrist device is suitable for self-measurement
      of blood pressure. It is advisable to perform an auscultatory comparative test at
      least once before buying such a device. 2. The oscillometric method for measuring
      blood pressure does not seem to be the proper method for epidemiologic studies
      and investigation of population groups in which lower diastolic pressure ranges
      are to assumed.

PMID- 7500920
TI  - [Cardiology update--II].

PMID- 7500921
TI  - [Value of corticoids in hematology/oncology in adulthood].

PMID- 7500922
TI  - [Pediatric tuberculosis in Germany. Current recommendations for diagnosis,
      prevention and therapy].

PMID- 7500923
TI  - [Cytoplasmic islet cell antibodies and GAD antibodies in diagnosis of diabetes].

PMID- 7500924
TI  - [Cardiac amyloidosis].

PMID- 7500925
TI  - [Public health: definition and goals].

PMID- 7500927
TI  - Outbreak of Salmonella serotype typhimurium infection associated with eating raw
      ground beef--Wisconsin, 1994.

PMID- 7500926
TI  - [Colon tumor and spontaneous clostridium myonecrosis (gas gangrene)].

PMID- 7500928
TI  - BB and pellet gun-related injuries--United States, June 1992-May 1994.

PMID- 7500929
TI  - Lead toxicity among bridge workers, 1994.

PMID- 7500930
TI  - Work-related injuries associated with falls during ice storms--National
      Institutes of Health, January 1994.

PMID- 7500931
TI  - Poverty and infant mortality--United States, 1988.

PMID- 7500932
TI  - Prevention and managed care: opportunities for managed care organizations,
      purchasers of health care, and public health agencies.
AB  - The rapid, extensive changes in the health-care system in the United States
      provide public health agencies with new opportunities for prevention-oriented
      relationships with the private health-care system. Managed care organizations
      (MCOs) are rapidly becoming a major source of health care for the beneficiaries
      of both employer-funded care and of the publicly funded programs, Medicaid and
      Medicare. In addition, MCOs represent organized care systems that often focus
      their efforts on defined populations and are accountable for desired outcomes,
      including prevention activities. In recognition of the potential role of managed
      care in prevention, in January 1995, CDC formed a Managed Care Working Group to
      develop recommendations for CDC for fostering the incorporation of prevention
      practices into managed care. This report presents these recommendations and
      approaches for their implementation, as well as background and case examples.

PMID- 7500933
TI  - Cloning and characterization of seven cDNAs for hyperosmolarity-responsive (HOR)
      genes of Saccharomyces cerevisiae.
AB  - Yeast cells can respond and adapt to osmotic stress. In our attempt to clarify
      the molecular mechanisms of cellular responses to osmotic stress, we cloned seven
      cDNAs for hyperosmolarity-responsive (HOR) genes from Saccharomyces cerevisiae by
      a differential screening method. Structural analysis of the clones revealed that
      those designated HOR1, HOR3, HOR4, HOR5 and HOR6 encoded glycerol-3-phosphate
      dehydrogenase (Gpd1p), glucokinase (Glk1p), hexose transporter (Hxt1p), heat
      shock protein 12 (Hsp12p) and Na+, K+, Li(+)-ATPase (Ena1p), respectively. HOR2
      and HOR7 corresponded to novel genes. Gpd1p is a key enzyme in the synthesis of
      glycerol, which is a major osmoprotectant in S. cerevisiae. Cloning of HOR1/GPD1
      as a HOR gene indicates that the accumulation of glycerol in yeast cells under
      hyperosmotic stress is, at least in part, caused by an increase in the level of
      GPDH protein. We performed a series of Northern blot analyses using HOR cDNAs as
      probes and RNAs prepared from cells grown under various conditions and from
      various mutant cells. The results suggested that all the HOR genes are regulated
      by common signal transduction pathways. However, the fact that they exhibited
      certain distinct responses indicated that they might also be regulated by
      specific pathways in addition to the common pathways. Ca2+ seemed to be involved
      in the signaling systems. In addition, Hog1p, one of the MAP kinases in yeast,
      appeared to be involved in the regulation of expression of HOR genes, although
      its function seemed to be insufficient for the overall regulation of expression
      of these genes.

PMID- 7500934
TI  - Partial inhibition of protein synthesis accelerates the synthesis of porphyrin in
      heme-deficient mutants of Escherichia coli.
AB  - Mutants of Escherichia coli defective in the HemA protein grow extremely poorly
      as the result of heme deficiency. A novel hemA mutant was identified whose rate
      of growth was dramatically enhanced by addition to the medium of low
      concentrations of translational inhibitors, such as chloramphenicol and
      tetracycline. This mutant (H110) carries mutation at position 314 in the hemA
      gene, which resulted in diminished activity of the encoded protein. Restoration
      of growth of H110 upon addition of the drugs mentioned above was due to
      activation of the synthesis of porphyrin. However, this activation was not
      characteristic exclusively of cells with this mutant hemA gene since it was also
      observed in a heme-deficient strain bearing the wild-type hemA gene. The
      activation did not depend on the promoter activity of the hemA gene, as indicated
      by studies with fusion genes. It appears that partial inhibition of protein
      synthesis via inhibition of peptidyltransferase can promote the synthesis of
      porphyrin by providing an increased supply of glutamyl-tRNA for porphyrin
      synthesis. Glutamyl-tRNA is the common substrate for peptidyltransferase and
      HemA.

PMID- 7500935
TI  - Isolation of temperature-sensitive mutants for mRNA capping enzyme in
      Saccharomyces cerevisiae.
AB  - The guanylyltransferase activity of mRNA capping enzyme catalyzes the transfer of
      GMP from GTP to the 5' terminus of mRNA. In Saccharomyces cerevisiae, the
      activity is carried on the alpha subunit of capping enzyme, the product of the
      CEG1 gene. We have isolated 10 recessive, temperature-sensitive mutations of
      CEG1; nine (ceg1-1 to ceg1-9) were isolated on a single-copy plasmid and the
      remaining one (ceg1-10) on a multicopy plasmid. The presence of ceg1-10 in
      multiple copies is essential for the viability of cells carrying the mutation,
      and a shift to the restrictive temperature resulted in rapid growth arrest of
      ceg1-10 cells, while growth rates of other mutants decreased gradually upon
      temperature upshift. Intragenic complementation was not observed for pairwise
      combinations of the mutations. Although the majority of the mutations occurred at
      the amino acid residues conserved between Ceg1 and the Schizosaccharomyces pombe
      homologue, none were located in the regions that are also conserved among viral
      capping enzymes and polynucleotide ligases. Guanylyltransferase activity of the
      mutant proteins as measured by covalent Ceg1-GMP complex formation was heat
      labile. The availability of these mutants should facilitate studies of the
      structure-function relationships of capping enzyme, as well as the roles and
      regulation of mRNA capping.

PMID- 7500937
TI  - Structural analysis of PKS1, a polyketide synthase gene involved in melanin
      biosynthesis in Colletotrichum lagenarium.
AB  - Albino mutants (Pks-) of Colletotrichum lagenarium form nonmelanized appressoria
      and possess little penetrating ability on the host plant. The defect in albino
      mutant 79215 (Pks-) is considered to lie in pentaketide biosynthesis and/or
      pentaketide cyclization during melanin biosynthesis. The cosmid pAC7, carrying
      the PKS1 gene, when transformed into the albino mutant restores the wild-type
      melanin phenotype. We have determine the DNA sequence and the transcriptional
      organization of the PKS1 gene. The PKS1 gene contains one open reading frame,
      consisting of 3 exons separated by two short introns. The predicted PKS1
      polypeptide consists of 2187 amino acids and shows significant similarities with
      other polyketide synthases, particularly that encoded by wA in Aspergillus
      nidulans, involved in conidial pigmentation. The PKS1 gene contains highly
      conserved beta-ketoacyl synthase, acetyl/malonyl transferase, and acyl carrier
      protein domains. We propose that the C. lagenarium PKS1 gene encodes a polyketide
      synthase involved in melanin biosynthesis.

PMID- 7500938
TI  - Evolution of the LINE-like I element in the Drosophila melanogaster species
      subgroup.
AB  - LINE-like retrotransposons, the so-called I elements, control the system of I-R
      (inducer-reactive) hybrid dysgenesis in Drosophila melanogaster. I elements are
      present in many Drosophila species. It has been suggested that active, complete I
      elements, located at different sites on the chromosomes, invaded natural
      populations of D. melanogaster recently (1920-1970). But old strains lacking
      active I elements have only defective I elements located in the chromocenter. We
      have cloned I elements from D. melanogaster and the melanogaster subgroup. In D.
      melanogaster, the nucleotide sequences of chromocentral I elements differed from
      those on chromosome arms by as much as 7%. All the I elements of D. mauritiana
      and D. sechellia are more closely related to the chromosomal I elements of D.
      melanogaster than to the chromocentral I elements in any species. No sequence
      difference was observed in the surveyed region between two chromosomal I elements
      isolated from D. melanogaster and one from D. simulans. These findings strongly
      support the idea that the defective chromocentral I elements of D. melanogaster
      originated before the species diverged and the chromosomal I elements were
      eliminated. The chromosomal I elements reinvaded natural populations of D.
      melanogaster recently, and were possibly introduced from D. simulans by
      horizontal transmission.

PMID- 7500936
TI  - Enhanced stability in vivo of a thermodynamically stable mutant form of yeast iso
      1-cytochrome c.
AB  - Previous work has established that the N57I amino acid replacement in iso-1
      cytochrome c from the yeast Saccharomyces cerevisiae causes an unprecedented
      increase in thermodynamic stability of the protein in vitro, whereas the N57G
      replacement diminishes stability. Spectrophotometric measurements of intact cells
      revealed that the N57I iso-1-cytochrome c is present at higher than normal levels
      in vivo. Although iso-1-cytochrome c turnover is negligible during aerobic
      growth, transfer of fully derepressed, aerobically grown cells to anaerobic
      growth conditions leads to reduction in the levels of all of the cytochromes.
      Pulse-chase experiments carried out under these anaerobic conditions demonstrated
      that the N57I iso-1-cytochrome c has a longer half-life than the normal protein.
      This is the first report of enhanced stability in vivo of a mutant form of a
      protein that has an enhanced thermodynamic stability in vitro. Although the N57I
      protein concentration is higher than the normal level, reduced growth in lactate
      medium indicated that the specific activity of this iso-1-cytochrome c in vivo is
      diminished relative to wild-type. On the other hand, the level of the
      thermodynamically labile N57G iso-1-cytochrome c was below normal. The in vivo
      levels of the N57I and N57G iso-1-cytochrome c suggest that proteins in the
      mitochondrial intermembrane space can be subjected to degradation, and that this
      degradation may play a role in controlling their normal levels.

PMID- 7500940
TI  - Genetic mapping of mitochondrial markers by recombinational analysis in
      Chlamydomonas reinhardtii.
AB  - The mitochondrial genome of Chlamydomonas reinhardtii is a 15.8 kb linear DNA
      molecule present in multiple copies. In crosses, the meiotic products only
      inherit the mitochondrial genome of the mating type minus (paternal) parent. In
      contrast mitotic zygotes transmit maternal and paternal mitochondrial DNA copies
      to their diploid progeny and recombinational events between molecules of both
      origins frequently occur. Six mitochondrial mutants unable to grow in the dark
      (dk- mutants) were crossed in various combinations and the percentages of wild
      type dk+ recombinants were determined in mitotic zygotes when all progeny cells
      had become homoplasmic for the mitochondrial genome. In crosses between strains
      mutated in the COB (apocytochrome b) gene and strains mutated in the COX1
      (subunit 1 of cytochrome oxidase) gene, the frequency of recombination was 13.7%
      (+/- 3.2%). The corresponding physical distance between the mutation sites was
      4.3 kb. In crosses between strains carrying mutations separated by about 20 bp, a
      recombinational frequency of 0.04% (+/- 0.02%) was found. Two other mutants not
      yet characterized at the molecular level were also used for recombinational
      studies. From these data, a linear genetic map of the mitochondrial genome could
      be drawn. This map is consistent with the positions of the mutation sites on the
      mitochondrial DNA molecule and thereby validates the method used to generate the
      map. The frequency of recombination per physical distance unit (3.2% +/- 0.7% per
      kilobase) is compared with those obtained for other organellar genomes in yeasts
      and Chlamydomonas.

PMID- 7500939
TI  - Mutations affecting the mitochondrial genes encoding the cytochrome oxidase
      subunit I and apocytochrome b of Chlamydomonas reinhardtii.
AB  - Mitochondrial mutants of the green alga Chlamydomonas reinhardtii that are
      inactivated in the cytochrome pathway of respiration have previously been
      isolated. Despite the fact that the alternative oxidase pathway is still active
      the mutants have lost the capacity to grow heterotrophically (dark + acetate) and
      display reduced growth under mixotrophic conditions (light + acetate). In crosses
      between wild-type and mutant cells, the meiotic progeny only inherit the
      character transmitted by the mt- parent, which indicates that the mutations are
      located in the 15.8 kb linear mitochondrial genome. Two new mutants (dum-18 and
      dum-19) have now been isolated and characterized genetically, biochemically and
      at the molecular level. In addition, two previously isolated mutants (dum-11 and
      dum-15) were characterized in more detail. dum-11 contains two types of deleted
      mitochondrial DNA molecules: 15.1 kb monomers lacking the subterminal part of the
      genome, downstream of codon 147 of the apocytochrome b (COB) gene, and dimers
      resulting from head-to-head fusion of asymmetrically deleted monomers (15.1 and
      9.5 kb DNA molecules, respectively). As in the wild type, the three other mutants
      contain only 15.8 kb mitochondrial DNA molecules. dum-15 is mutated at codon 140
      of the COB gene, a serine (TCT) being changed into a tyrosine (TAC). dum-18 and
      dum-19 both inactivate cytochrome c oxidase, as a result of frameshift mutations
      (addition or deletion of 1 bp) at codons 145 and 152, respectively, of the COX1
      gene encoding subunit I of cytochrome c oxidase. In a total of ten respiratory
      deficient mitochondrial mutants characterized thus far, only mutations located in
      COB or COX1 have been isolated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500942
TI  - A new Escherichia coli gene, fdrA, identified by suppression analysis of dominant
      negative FtsH mutations.
AB  - An Escherichia coli membrane protein, FtsH, has been implicated in several
      cellular processes, including integration of membrane proteins, translocation of
      secreted proteins, and degradation of some unstable proteins. However, how it
      takes part in such diverse cellular events is largely unknown. We previously
      isolated dominant negative ftsH mutations and proposed that FtsH functions in
      association with some other cellular factor(s). To test this proposal we isolated
      multicopy suppressors of dominant negative ftsH mutations. One of the multicopy
      suppressor clones contained an N-terminally truncated version of a new gene that
      was designated fdrA. The FdrA fragment suppressed both of the phenotypes-
      increased abnormal translocation of a normally cytoplasmic domain of a model
      membrane protein and retardation of protein export--caused by dominant negative
      FtsH proteins. The intact fdrA gene (11.9 min on the chromosome) directed the
      synthesis of a 60 kDa protein in vitro.

PMID- 7500941
TI  - The ACC1 gene, encoding acetyl-CoA carboxylase, is essential for growth in
      Ustilago maydis.
AB  - Acetyl-CoA carboxylase [ACCase; acetyl-CoA:carbon dioxide ligase (ADP forming),
      EC 6.4.1.2] catalyses the ATP-dependent carboxylation of acetyl-CoA to form
      malonyl-CoA. We have amplified a fragment of the biotin carboxylase (BC) domain
      of the Ustilago maydis acetyl-CoA carboxylase (ACC1) gene from genomic DNA and
      used this amplified DNA fragment as a probe to recover the complete gene from a
      lambda EMBL3 genomic library. The ACC1 gene has a reading frame of 6555
      nucleotides, which is interrupted by a single intron of 80 bp in length. The gene
      encodes a protein containing 2185 amino acids, with a calculated M(r) of 242,530;
      this is in good agreement with the size of ACCases from other sources. Further
      identification was based on the position of putative binding sites for acetyl
      CoA, ATP, biotin and carboxybiotin found in other ACCases. A single ACC1 allele
      was disrupted in a diploid wild-type strain. After sporulation of diploid
      disruptants, no haploid progeny containing a disrupted acc1 allele were
      recovered, even though an exogenous source of fatty acids was provided. The data
      indicate that, in U. maydis, ACCase is required for essential cellular processes
      other than de novo fatty acid biosynthesis.

PMID- 7500943
TI  - Yeast Kre1p is a cell surface O-glycoprotein.
AB  - The Saccharomyces cerevisiae KRE1 gene encodes a secretory protein required for
      the production of the cell wall polymer (1-->6)-beta-glucan. Here we report
      further characterization of the KRE1 gene product, Kre1p. A functional, epitope
      tagged Kre1p is shown to be highly modified in a SEC53-dependent manner. Kre1p is
      O-glycosylated, but the basis for the majority of its post-translational
      modification is unknown. Fractionation of Kre1p reveals a cell wall-associated
      form and a less abundant membrane-associated species. Indirect
      immunoflurorescence demonstrates that Kre1p localizes to the cell surface, where
      it becomes concentrated at the surface of mother cells. Such a localization of
      Kre1p seems to parallel the CAL1/CSD2-dependent cell wall deposition of chitin
      found in S. cerevisiae, and is consistent with evidence from Schizophyllum
      commune that (1-->6)-beta-glucan accumulates during maturation of the subapical
      region of the wall distal to the hyphal tip.

PMID- 7500945
TI  - Easel, a gypsy LTR-retrotransposon in the Salmonidae.
AB  - Despite the close similarities between retroviruses and the gypsy/Ty3 group of
      LTR-retrotransposons their host ranges are largely distinct: the retroviruses are
      found only in vertebrates, whereas the gypsy LTR-retrotransposons are almost
      exclusively restricted to invertebrates, plants and fungi. Here we report the
      amplification by PCR, and characterisation, of one of the first LTR
      retrotransposons to be discovered in vertebrates--in several members of the
      piscine family Salmonidae. Phylogenetic analysis of this retroelement, termed
      easel, indicates that it is probably a phylogeneticaly basal member of the gypsy
      group of LTR-retrotransposons and occurs in some of the same species from which
      retroviruses have previously been isolated. Thus some members of the Salmonidae
      are the first organisms known to harbour both retroviral branch elements and the
      gypsy LTR-retrotransposon branch elements. This creates an overlap in the host
      ranges of the two retroelement families.

PMID- 7500946
TI  - Secretion of active beta-lactamase to the medium mediated by the Escherichia coli
      haemolysin transport pathway.
AB  - An in frame gene fusion containing the coding region for mature beta-lactamase
      and the 3'-end of hylA encoding the haemolysin secretion signal, was constructed
      under the control of a lac promoter. The resulting 53 kDa hybrid protein was
      specifically secreted to the external medium in the presence of the haemolysin
      translocator proteins, HlyB and HlyD. The specific activity of the beta-lactamase
      portion of the secreted protein (measured by the hydrolysis of penicillin G),
      approximately 1 U/microgram protein, was close to that of authentic, purified TEM
      beta-lactamase. This is an important example of a hybrid protein that is
      enzymatically active, and secreted via the haemolysin pathway. Previous studies
      have indicated that haemolysin is secreted directly into the medium, bypassing
      the periplasm, to which beta-lactamase is normally targeted. This study
      indicated, therefore, that normal folding of an active beta-lactamase, can occur,
      at least when fused to the HlyA C-terminus, without the necessity of entering the
      periplasm. Despite the secretion of approximately 5 micrograms/ml levels of the
      active beta-lactamase fusion into the medium, there was maximally only a 50%
      detectable increase in the LD50 for resistance to ampicillin at the individual
      cell level. This result suggests that, normally, resistance to ampicillin
      requires a high concentration of the enzyme close to killing targets, i.e. in the
      periplasm, in order to achieve significant levels of protection.

PMID- 7500947
TI  - The transposable element mariner can excise in non-drosophilid insects.
AB  - Plasmid-based excision assays performed in embryos of two non-drosophilid species
      using the mariner transposable element from Drosophila mauritiana resulted in
      empty excision sites identical to those observed after the excision of mariner
      from D. mauritiana chromosomes. In the presence of the autonomous mariner element
      Mos1, excision products were recovered from D. melanogaster, D. mauritiana and
      the blowfly Lucilia cuprina. When a hsp82 heat shock promoter-Mos1 construct was
      used to supply mariner transposase, excision products were also recovered from
      the Queensland fruitfly Bactrocera tryoni. Analysis of DNA sequences at empty
      excision sites led us to hypothesise that the mariner excision/repair process
      involves the formation of a heteroduplex at the excision breakpoint. The success
      of these assays suggests that they will provide a valuable tool for assessing the
      ability of mariner and mariner-like elements to function in non-drosophilid
      insects and for investigating the basic mechanisms of mariner excision and
      repair.

PMID- 7500948
TI  - Excision of chromosomal DNA loops by treatment of permeabilised cells with Bal 31
      nuclease.
AB  - The specificity of long-range fragmentation of human nucleolar genes by Bal 31
      nuclease was studied using fractionation of cleavage products by pulsed field gel
      electrophoresis, followed by Southern hybridization. It was found that limited
      treatment of permeabilised cells with this nuclease results in accumulation of
      DNA scissions in matrix attachment areas. Consequently, chromosomal DNA loops and
      their oligomers are released from the genome.

PMID- 7500944
TI  - Structural genes for salicylate biosynthesis from chorismate in Pseudomonas
      aeruginosa.
AB  - Salicylate is a precursor of pyochelin in Pseudomonas aeruginosa and both
      compounds display siderophore activity. To elucidate the salicylate biosynthetic
      pathway, we have cloned and sequenced a chromosomal region of P. aeruginosa PAO1
      containing two adjacent genes, designated pchB and pchA, which are necessary for
      salicylate formation. The pchA gene encodes a protein of 52 kDa with extensive
      similarity to the chorismate-utilizing enzymes isochorismate synthase,
      anthranilate synthase (component I) and p-aminobenzoate synthase (component I),
      whereas the 11 kDa protein encoded by pchB does not show significant similarity
      with other proteins. The pchB stop codon overlaps the presumed pchA start codon.
      Expression of the pchA gene in P. aeruginosa appears to depend on the
      transcription and translation of the upstream pchB gene. The pchBA genes are the
      first salicylate biosynthetic genes to be reported. Salicylate formation was
      demonstrated in an Escherichia coli entC mutant lacking isochorismate synthase
      when this strain expressed both the pchBA genes, but not when it expressed pchB
      alone. By contrast, an entB mutant of E. coli blocked in the conversion of
      isochorismate to 2,3-dihydro-2,3-dihydroxybenzoate formed salicylate when
      transformed with a pchB expression construct. Salicylate formation could also be
      demonstrated in vitro when chorismate was incubated with a crude extract of P.
      aeruginosa containing overproduced PchA and PchB proteins; salicylate and
      pyruvate were formed in equimolar amounts. Furthermore, salicylate-forming
      activity could be detected in extracts from a P. aeruginosa pyoverdin-negative
      mutant when grown under iron limitation, but not with iron excess. Our results
      are consistent with a pathway leading from chorismate to isochorismate and then
      to salicylate plus pyruvate, catalyzed consecutively by the iron-repressible PchA
      and PchB proteins in P. aeruginosa.

PMID- 7500950
TI  - Horizontal gene transfer: regulated expression of a tobacco homologue of the
      Agrobacterium rhizogenes rolC gene.
AB  - A tobacco homologue (trolC) of the rolC gene of the Agrobacterium rhizogenes Ri
      plasmid was cloned and sequenced from Nicotiana tabacum L. cv. Havana 425. The
      coding region of trolC is similar in sequence (69-87% for DNA and 54-89% for the
      deduced amino acid sequence) to rolC genes of the agropine, mannopine, and
      mikimopine strains of Ri-plasmids and the N. glauca rolC homologue. Southern
      analyses showed that trolC is encoded by a small gene family derived from the
      tomentosiformis ancestor of tobacco. This suggests that trolC resulted from an
      ancient transfer of DNA between A. rhizogenes and a progenitor of modern tobacco.
      Transcripts of trolC were detected in three morphologically distinct cultivars of
      tobacco. trolC mRNA accumulated in young leaves and shoot tips, but not in lower
      leaves and roots of mature plants. Accumulation of trolC mRNA in cultured leaf
      tissues was strongly down-regulated by auxin and induced by cytokinin. These
      results are of particular interest because they suggest that a gene of bacterial
      origin introduced during evolution can have a function in a modern plant.

PMID- 7500949
TI  - Adaptation to high-salt stress in Saccharomyces cerevisiae is regulated by
      Ca2+/calmodulin-dependent phosphoprotein phosphatase (calcineurin) and cAMP
      dependent protein kinase.
AB  - Ca2+/calmodulin-dependent phosphoprotein phosphatase (calcineurin, PP2B) of
      Saccharomyces cerevisiae is implicated in adaptation to high-salt conditions.
      Calcineurin mediates high salt-induced expression of the ENA1/PMR2 gene encoding
      the P-type ATPase, which is suggested to be involved in Na+ efflux. We identified
      the PDE1 gene encoding the low-affinity cAMP phosphodiesterase as a multicopy
      suppressor of the Li(+)- and Na(+)-sensitive calcineurin null mutant, suggesting
      that cAMP is a negative regulator of adaptation to high-salt stress. Genetic
      analysis indicated that calcineurin and cAMP act antagonistically in a common
      pathway for adaptation. The bcy1 disruption, which leads to constitutive cAMP
      dependent protein kinase (PKA) activity inhibited high NaCl-induced expression of
      the ENA1/PMR2 gene, caused an elevation of the intracellular Na+ level and a
      growth defect in high-NaCl medium, all of which were analogous to the defects of
      a calcineurin mutant. A reduced cAMP level resulting from multiple copies of the
      PDE1 gene caused increased expression of the ENA1/PMR2 gene in response to high
      NaCl. We propose a model for the regulation of cation homeostasis, in which
      calcineurin antagonizes PKA to activate transcription of the ENA1/PMR2 gene in
      response to high-salt conditions.

PMID- 7500951
TI  - Cloning and nucleotide sequence of fosfomycin biosynthetic genes of Streptomyces
      wedmorensis.
AB  - The biosynthetic pathway for production of the antibiotic fosfomycin by
      Streptomyces wedmorensis consists of four steps including the formation of a C-P
      bond and an epoxide. Fosfomycin production genes were cloned from genomic DNA
      using S. wedmorensis mutants blocked at different steps of the biosynthetic
      pathway. Four genes corresponding to each of the biosynthetic steps were found to
      be clustered in a DNA fragment of about 5 kb. Nucleotide sequencing of a large
      fragment revealed the presence of ten open reading frames, including the four
      biosynthetic genes and six genes with unknown functions.

PMID- 7500952
TI  - The role of subterminal sites of transposable element Ds of Zea mays in excision.
AB  - Transposition depends on DNA sequences located at or near the termini of the
      transposon. In the maize transposable element Ds, these sequences were studied by
      site-directed mutagenesis followed by a transient excision assay in Petunia
      protoplasts. The transposase-binding AAACGG motifs found in large numbers in the
      element are important, but none of them is in itself indispensable, for excision.
      However, mutation of an isolated motif at the 3' end considerably reduced
      excisability. The inverted termini were confirmed to be indispensable. Point
      mutations in regions outside the inverted termini of Ds and not located in the
      transposase-binding motifs had, in some cases, a pronounced effect on excision
      frequency. The implications of these findings are discussed.

PMID- 7500953
TI  - A C-terminal region of the Saccharomyces cerevisiae transcription factor ADR1
      plays an important role in the regulation of peroxisome proliferation by fatty
      acids.
AB  - The Saccharomyces cerevisiae transcriptional activator ADR1, which controls ADH2
      gene expression, was shown to be involved in the regulation of peroxisome
      proliferation. To study the mode of action of ADR1, we compared strains carrying
      the adr1-1 mutation, high or low copy numbers of the ADR1 gene, the constitutive
      allele ADR1-5c, and 3'-deletions of ADR1. High ADR1 gene dosage increased the
      transcription of genes encoding peroxisomal proteins as compared to one copy of
      the ADR1 gene. Furthermore, overexpression of ADR1 under ethanol growth
      conditions induced the proliferation of peroxisomal structures. The organelles
      were observed to be localized in clusters, a typical feature of peroxisomes
      induced by oleic acid. In contrast, the ADR1-5c allele, which induces ADH2
      expression to a level comparable to that of high ADR1 gene dosage was found to
      have only a small effect. An analysis of functional domains of the ADR1 protein
      revealed that the N-terminal 220 amino acids of ADR1 were sufficient for wild
      type levels of transcription of the FOX2, FOX3, and PAS1 genes, but the entire
      ADR1 protein was required for complete induction of the CTA1 gene and for growth
      oleic acid medium. Our data suggest that a functional domain of the ADR1 protein
      localized between residues 643 and 1323 is required for the induction of
      peroxisomal structures and for the utilization of oleic acid.

PMID- 7500954
TI  - Hyperspeckled mutants of Schizosaccharomyces pombe: frequent mating-type
      switching without detectable double-strand breaks.
AB  - Mating-type (MT) switching in homothallic (h90) strains of Schizosaccharomyces
      pombe is initiated by a DNA double-strand break (DSB) at the distal end of the
      expression cassette mat1. The cis-acting smt-s1 mutation C13-P11 reduces the
      frequency of MT switching. It is a small deletion mapping approximately 50 bp
      distal to the site of the DSB. From the h90 smt-s1 strain we isolated 13 mutants
      with a hyperspeckled iodine reaction. In these mutants the frequency of MT
      switching is increased. The mutations define nine different hsp genes, none of
      which maps in or close to the MT region. We tested one mutant of each gene for
      the presence of DSBs at mat1. Curiously, in none of the h90 smt-s1 hsp strains
      could DSBs be detected, although some sporulate nearly as efficiently as the h90
      smt-n wild type. The hsp mutations show no effect in smt-0 strains; the smt-0
      deletion abolishes MT switching completely. Furthermore, we tested the
      interaction of hsp1-1 with swi1, swi2 and swi7 mutations. hsp1-1 has no effect in
      swi2 strains, whereas it increases MT switching in swi7 and, to a lesser degree,
      in swi1 mutants.

PMID- 7500955
TI  - Purification of a heteromeric CCAAT binding protein from Neurospora crassa.
AB  - Expression of the Neurospora crassa am (NADP-specific glutamate dehydrogenase)
      gene is controlled by two upstream enhancer-like elements designated URSam alpha
      and URSam beta. URSam alpha is localized between - 1.3 and - 1.4 kb with respect
      to the major transcriptional start site. Deletion of a 90 bp sequence containing
      this element resulted in the loss of approximately 50% of normal glutamate
      dehydrogenase expression. Gel mobility shift analysis indicated that a nuclear
      protein from Neurospora binds in a specific manner to sequences within the 90 bp
      fragment. We have now used a combination of ion-exchange and affinity
      chromatography to purify this nuclear protein, which we call Am Alpha Binding
      protein (AAB). The activity was monitored by gel shift analysis. The protein was
      purified more than 14,000-fold with a yield of approximately 7%. The purified
      protein appears as a heteromer on denaturing polyacrylamide gel electrophoresis,
      with only two strong bands visible in silver-stained preparations. One band has
      an apparent molecular mass of 40 kDa, the other appears as a doublet with an
      apparent molecular mass of 30 kDa. DNAse I protection analysis indicated a
      protected region consisting of 30 bp, which contains a CCAAT pentanucleotide
      motif. Mutagenesis of the CCAAT motif abolished the binding of AAB to the DNA
      fragment.

PMID- 7500956
TI  - The effects of a ring chromosome on the meiotic segregation of other chromosomes
      in Saccharomyces cerevisiae.
AB  - Meiotic chromosome segregation must occur with high fidelity in order to prevent
      the generation of aneuploid cells. We have previously described the
      identification and genetic characterization of a yeast mutant with defects in
      meiotic sister-chromatid segregation. We attributed the phenotype in this mutant
      to a dominant allele, which we referred to as SID1-1. These mutants appeared to
      exhibit high levels of non-disjunction and precocious separation of sister
      chromatids of chromosome III, as well as precocious separation of sister
      chromatids of chromosome VIII and a univalent artificial chromosome. We show here
      that the unusual meiotic behavior of chromosome III in these strains is due to
      the presence of a ring III chromosome, rather than a mutant gene. Additional
      experiments demonstrate that a ring III/rod III pair alters the meiotic
      segregation of a univalent artificial chromosome.

PMID- 7500957
TI  - Regulation of the expression of three housekeeping genes encoding subunits of the
      Neurospora crassa vacuolar ATPase.
AB  - The vacuolar ATPase is a complex enzyme and is encoded by at least nine genes,
      which appear to be scattered throughout the genome. We have examined the vma-1
      vma-2, and vma-3 genes, which encode subunits present in multiple copies within
      the Neurospora crassa vacuolar ATPase. We wished to see if the expression of
      these genes is coordinately regulated and if these genes contain similar promoter
      elements. A region was sequenced of approximately 1 kb located upstream of the
      protein coding region for each gene. Several sequence elements were found in
      similar positions in each of the three genes. Each of the genes had several
      strong transcription initiation sites, clustered within 13-60 bp and located 112
      193 bp upstream of the translation start site. The size and abundance of the RNA
      transcripts was also determined: the amount of RNA transcribed from each gene was
      roughly proportional to the numbers of each subunit present in the enzyme. A
      series of plasmids was constructed containing parts of the putative promoter
      region fused to beta-galactosidase. Analysis of these plasmids indicated that the
      essential region of the vma promoters lies within 370 bp of the protein coding
      region. Overall, the vma genes appear to have similar characteristics to
      "housekeeping" genes described in other organisms.

PMID- 7500958
TI  - Effects of different growth conditions on the in vivo activity of the tandem
      Escherichia coli ribosomal RNA promoters P1 and P2.
AB  - We have analyzed the relative activities of the Escherichia coli ribosomal RNA
      promoters P1 and P2 in vivo under different physiological conditions. Promoter
      efficiencies were determined by quantitative comparison of the transcript
      specific primer extension products obtained from total RNA preparations. Cells
      were analyzed at different stages of the growth cycle, at different growth rates,
      and under conditions of stringent control. In addition, the rRNA gene dosage was
      altered by transformation with plasmids containing additional rrnD or rrnB
      transcription units, or rRNA operons in which one of the tandem promoters (P1)
      had been deleted. Under conditions of amino acid starvation (stringent control)
      we observed the expected strong reduction in P1-directed transcription. In
      contrast to the previous assumption that the P2 promoter is not regulated, we
      simultaneously noticed a smaller but significant repression of P2-directed
      transcription. In strains in which the rRNA gene dosage was increased by
      transformation with plasmids bearing rRNA transcription units, a similar degree
      of repression was observed. Repression of the P1 promoter activity was increased,
      however, when cells contained extra rRNA operons with P2 promoters only. As
      demonstrated under stringent control conditions, changes in the growth cycle also
      affected the activity of promoters P1 and P2. A greater proportion of P2-derived
      transcripts was observed when cells changed from exponential to stationary growth
      or if cultures were grown in minimal medium. Under steady-state, slow growth
      conditions (minimal medium) we obtained evidence showing that the ratio of P1/P2
      transcription products is much lower for cells with extra rrnB as compared to
      extra rrnD operons or cells lacking extra rRNA operons, implying an operon
      specific regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7500961
TI  - Environmental and occupational medicine in clinical practice. Introduction.

PMID- 7500960
TI  - Comparative mapping in grasses. Oat relationships.
AB  - The development of RFLP linkage maps in hexaploid and diploid oat allows us to
      study genetic relationships of these species at the DNA level. In this report, we
      present the extension of a previously developed diploid oat map (Avena atlantica
      x A. hirtula) and its molecular-genetic relationships with wheat, rice and maize.
      Examination of 92-99% of the length of the oat genome map with probes common to
      Triticeae species, rice or maize showed that 84, 79 and 71%, respectively, was
      conserved between these species and oat. Generally, the orders of loci among
      chromosomes homoelogous to oat chromosomes A and D were the most conserved and
      those of chromosomes homoeologous to oat chromosome G were the least conserved.
      Conservation was observed for blocks ranging from whole chromosomes 101 cM long
      to small segments 2.5 cM long containing two loci. Comparison of the homoeologous
      segments of Triticeae, rice and maize relative to oat indicated that certain
      regions have been maintained in all four species. The relative positions of major
      genes governing traits such as seed storage proteins and resistance to leaf rusts
      have been conserved between cultivated oat and Triticeae species. Also, the
      locations of three vernalization/or photoperiod response genes identified in
      hexaploid oat correspond to the locations of similar genes in homoeologous
      chromosomes of wheat, rice or maize. The locations of the centromeres for six of
      the seven oat chromosomes were estimated based on the homoeologous segments
      between oat and Triticeae chromosomes.

PMID- 7500959
TI  - Recognition and alignment of homologous DNA sequences between minichromosomes and
      single-stranded DNA promoted by RecA protein.
AB  - The incorporation of DNA into nucleosomes and higher-order forms of chromatin in
      vivo creates difficulties with respect to its accessibility for cellular
      functions such as transcription, replication, repair and recombination. To
      understand the role of chromatin structure in the process of homologous
      recombination, we have studied the interaction of nucleoprotein filaments,
      comprised of RecA protein and ssDNA, with minichromosomes. Using this paradigm,
      we have addressed how chromatin structure affects the search for homologous DNA
      sequences, and attempted to distinguish between two mutually exclusive models of
      DNA-DNA pairing mechanisms. Paradoxically, we found that the search for
      homologous sequences, as monitored by unwinding of homologous or heterologous
      duplex DNA, was facilitated by nucleosomes, with no discernible effect on
      homologous pairing. More importantly, unwinding of minichromosomes required the
      interaction of nucleoprotein filaments and led to the accumulation of circular
      duplex DNA sensitive to nuclease P1. Competition experiments indicated that
      chromatin templates and naked DNA served as equally efficient targets for
      homologous pairing. These and other findings suggest that nucleosomes do not
      impede but rather facilitate the search for homologous sequences and establish,
      in accordance with one proposed model, that unwinding of duplex DNA precedes
      alignment of homologous sequences at the level of chromatin. The potential
      application of this model to investigate the role of chromosomal proteins in the
      alignment of homologous sequences in the context of cellular recombination is
      considered.

PMID- 7500962
TI  - An urban community faces an environmental hazard: "let them eat chromium"?

PMID- 7500963
TI  - Effects in society of ionizing radiation.

PMID- 7500965
TI  - Health risk implications of magnetic field exposures.
AB  - Magnetic field exposures pose serious questions to the public. The science is not
      sufficiently clear or consistent to result in a consensus. Some scientists view
      the data as strongly suggestive and argue that if the association is true, the
      ubiquity of exposure may be resulting in a marked underestimation of the actual
      risk. Others argue that the inconsistencies in the data and the specific
      limitations of the studies suggest that there is no association and no reason for
      concern. The state of the science is such that a definitive resolution is
      unlikely in the next few years. In light of this uncertainty, I believe that the
      most prudent course of action is the prevention or limitation of exposure where
      feasible at limited cost and inconvenience. Be it at home or at work, prevention
      of exposure is simply good public health practice.

PMID- 7500964
TI  - Pregnancy, lactation, and menopause: how physiology and gender affect the
      toxicity of chemicals.
AB  - We explore ways in which biological events and nonbiological gender factors in
      women's lives can mediate the toxicity of chemicals to women. We examine the
      physiologic changes that accompany pregnancy, lactation, and menopause in order
      to discuss how these changes might influence the target organ dose and
      distribution of toxic chemicals within women's bodies. We suggest that the
      interactions between divalent metals and calcium metabolism and those between
      lipophilic chemicals and fat metabolism could modulate the toxicity of metallic
      and lipophilic toxins in women over the course of a lifetime. These hypotheses
      need careful research consideration.

PMID- 7500966
TI  - Lead poisoning.

PMID- 7500967
TI  - Incineration: health and environmental consequences.
AB  - Incineration is considered one of the four primary ways to manage solid wastes,
      in conjunction with source reduction and reuse, recycling-composting, and
      landfilling. Incineration is currently used to destroy household and
      institutional solid waste, hazardous chemical waste, and medical and biological
      waste by reducing volume and destroying some harmful constituents. The process of
      incineration induces chemical changes that may produce harmful products that can
      escape through the stack, causing air pollution, or that can remain in the bottom
      ash, eventually finding a way into landfills. Although sound engineering design
      and operation can theoretically eliminate most harmful pollutants, strong
      institutional controls are required to assure that incinerators are maintained
      and operated according to specifications. Incineration is often viewed as a "cop
      out," avoiding the socioeconomically complex changes required to reduce the
      generation of solid waste. Incineration should be incorporated on a limited basis
      into a context of comprehensive approaches to source reduction, recycling, and
      reuse.

PMID- 7500968
TI  - Human exposure to toxic materials. The New York-New Jersey metropolitan region.

PMID- 7500970
TI  - Shaping environmental research: the Lead Industries Association 1928-1946.

PMID- 7500972
TI  - Medical and public health approaches to asbestos disease.
AB  - Asbestos is known to cause a wide range of nonmalignant and malignant disease
      among occupationally and environmentally exposed individuals. Lung cancer and
      mesothelioma are of special importance. X-rays are evaluated utilizing the ILO
      classification, and the clinical signs and symptoms of many chronic lung diseases
      may occur. The fibrous nature of asbestos appears to be important, and fiber size
      plays a role in carcinogenic outcome. Because of the significant legal and public
      health implications of exposure, it appears that purposeful obfuscation of
      asbestos science has taken place. There are also worldwide efforts to shift
      patterns of use and manufacturing, leading to a wider dissemination of death and
      disease, especially when coupled with spreading tobacco usage.

PMID- 7500969
TI  - Alternative sources of risk estimates for cancer effects of radiation.

PMID- 7500973
TI  - Clinical recognition of occupational and environmental disease.

PMID- 7500971
TI  - Occupation and environment in internal medicine: sentinel events and trigger
      questions.
AB  - Patients who undergo sentinel events indicate a breakdown in the chain of
      prevention and protection. Because most work- or environmentally induced
      illnesses and disabilities produce nonspecific or late symptoms and signs, the
      search for exposures to physical, toxic, ergonomic, or sociopsychological events
      that induce these sentinel events has to be based on systematic investigative
      routine, and not on the physician's mere awareness. Routine use of five "trigger"
      questions to identify jobs, tasks, exposures, symptoms, and other persons at risk
      can be effective, quick, and inexpensive in the search for preventable illness
      related to work or environment in the sentinel patient, especially when illness
      persists, recurs, or progresses or occurs in others. Sometimes, others can be
      helped when it is too late to do anything for the sentinel individual. This holds
      true for the relatively simple situations of one exposure and one outcome and for
      settings in which there are many exposures or many diseases in one or many
      patients. The newer set of "clean" environments that include ergonomic and
      sociopsychological hazards and stress at the work-station have produced new
      sentinel events. Knowledge of the impact of macro-environmental hazards
      presupposes familiarity with their impact on individual risks. Using the sentinel
      event to promote prevention of hazardous exposures means opportunities for
      reducing unnecessary risk in individuals and small groups. Opportunities for
      prevention arise when sentinel events occur at the time of exposure. Where there
      is latency between exposure and outcome, an anticipatory approach based on
      awareness of future risks from preventable current exposures is needed. The
      search for external exposures that have already occurred and for those that are
      preventable should be a routine part of internal medicine.

PMID- 7500974
TI  - Tar melanosis.

PMID- 7500975
TI  - Hyperthermic induction of premature chromosome condensation in human lymphocytes.
AB  - Hyperthermic induction of chromosomal aberrations was examined in human
      lymphocytes. For this purpose, whole blood cultures were exposed to an elevated
      temperature (43 degrees C) at the 46th h of culture initiation, followed by 24 h
      of recovery. Detailed chromosomal analysis showed significantly higher levels of
      aberrations as compared to control cultures of the same individuals. These
      aberrations include breaks, gaps of both chromosome and chromatid type,
      aneuploidy and high levels of polyploidy. The interesting observation was the
      occurrence of S-phase premature chromosome condensation (PCC). The S-phase PCC
      observed here could be due to asynchronous nuclei induced by hyperthermia. A
      possible interpretation for the occurrence of asynchronous nuclei leading to the
      induction of S-phase PCC is discussed.

PMID- 7500977
TI  - Induction of high SCEs in normal cells by 11-12 kDa plasma protein overexpressed
      in some sleep deprived volunteers.
AB  - The present study confirmed our earlier preliminary observation of induction of
      high SCEs in 1 day sleep-deprived healthy volunteers and showed that the property
      of induction of high SCE by after-sleep-deprived (ASD) plasma was retained both
      in 50% ammonium sulphate precipitates and in the dialysed plasma using a membrane
      of 12 kDa porocity. Further, nitrocellulose bound 11-12 kDa electrophoretically
      isolated plasma protein from ASD individuals was found responsible for the
      induction of high SCE in normal whole blood cultures. A short exposure of 3 h to
      5% ASD plasma was enough to induce significantly high SCEs in normal lymphocytes
      which had undergone 2 replication cycles after the exposure to this factor.

PMID- 7500976
TI  - Stage-specific DNA synthesis of rat spermatogenesis as an indicator of genotoxic
      effects of vinblastine, mitomycin C and ionizing radiation on rat spermatogonia
      and spermatocytes.
AB  - We have studied the effects of three known mutagens: vinblastine sulphate,
      mitomycin C and local irradiation of testes on the stage-specific DNA synthesis
      in the rat testis by using transillumination assisted microdissection of rat
      seminiferous tubules. It enables us to investigate the sensitivity of different
      types of spermatogonia and preleptotene spermatocytes to the genotoxic effects of
      these agents. According to our results, spermatogonia and preleptotene
      spermatocytes are quite resistant to the action of vinblastine at the treatment
      times and the doses used. After treatment with mitomycin C, type A2, A3 and A4
      spermatogonia seem to be the first cell types affected, which shows itself as a
      reduction in the DNA synthesis at stages I, II-III, XIII-XIV of the epithelial
      cycle two and/or three days after the treatment. It also seems that they are
      mostly affected during the S-phase of their cell cycles. In addition,
      preleptotene spermatocytes are also sensitive to the action of mitomycin C when
      they are treated in the G1 phase of the cell cycle. The local irradiation of 3 Gy
      has severe effects on the spermatogonia of rat testis which can be seen already
      18 h after the treatment and becomes more evident 42 and 66 h after the treatment
      as a reduction of DNA synthesis at stages XII-V. Type A spermatogonia (A1-A4)
      seem to be the most sensitive cell types to the action of irradiation. This study
      indicates that the novel method of stage-specific DNA synthesis in rat
      spermatogenesis allows detailed studies of sensitivities in differentiating
      spermatogonia to genotoxic agents.

PMID- 7500978
TI  - Synthesis of poly(ADP-ribose) in asbestos treated rat pleural mesothelial cells
      in culture.
AB  - To investigate the origin of DNA repair in rat pleural mesothelial cells (RPMC)
      exposed to asbestos fibers, poly(ADP-ribose) polymerase (PARP) activity was
      measured in the asbestos-treated cells. As bleomycin has been shown to activate
      poly(ADP-ribose) synthesis in several cell systems, the response to bleomycin
      with regard to PARP assay was first investigated. Bleomycin produced a dose
      dependent increase of poly(ADP-ribose) synthesis in RPMC. Likewise both
      chrysotile and crocidolite fibers produced a concentration-dependent PARP
      activation indicating that the formation of DNA strand breaks is one type of
      damage produced by asbestos in RPMC. Enhancement of DNA repair, assessed by the
      measurement of [3H] methylthymidine incorporation in growth arrested cells, was
      not detectable in the presence of 3-methoxybenzamide (3-MBA), a PARP inhibitor,
      confirming a relation between PARP activation and DNA repair. The participation
      of DNA breakage in asbestos toxicity on RPMC was determined by the colorimetric 3
      4(5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. There was
      no relationship between DNA breakage and cytotoxicity since the use of PARP
      inhibitors did not change cell viability. These results indicate that asbestos
      produce DNA damage that is repaired in RPMC.

PMID- 7500979
TI  - Sister-chromatid exchanges in cattle: breed, sex and BrdU dose effects.
AB  - The spontaneous incidence of sister-chromatid exchanges (SCE) was investigated in
      a group of cattle, composed of 21 animals of both sexes and from two different
      breeds (Fleckvieh and Pirenaica). Peripheral lymphocytes of these animals were
      cultured in three different bromodeoxyuridine (BrdU) concentrations: 5, 15 and 30
      micrograms/ml. The work was carried out following a randomized block design.
      Among the analyzed sources of variability, group, breed and BrdU dose factors had
      significant effects on the SCE frequency. No differences between sexes were
      found. Comparisons of the BdrU doses showed that the 5 micrograms/ml dose
      differed from both the 15 and 30 micrograms/ml doses, whereas the 15 and 30
      micrograms/ml doses did not differ from each other. The results indicate that the
      breed of cattle as well as the BrdU dose chosen for the analysis must be
      considered when the SCE test is used for the biomonitoring of environmental
      mutagens.

PMID- 7500981
TI  - Of mice and mutants: target size and sensitivity.

PMID- 7500980
TI  - Mutation spectrum of 2-chloroethyl methanesulfonate in Drosophila melanogaster
      premeiotic germ cells.
AB  - The 2-chloroethyl methanesulfonate (2ClEMS)-induced alcohol dehydrogenase (Adh)
      null germline mutation frequency in treated Drosophila melanogaster second instar
      larval gonia was two orders of magnitude greater than the spontaneous mutation
      frequency. DNA sequence analysis of 83 Adh null mutations showed that 40
      mutations of independent origin were at 23 sites in the Adh gene. The mutation
      spectrum contained only GC-->AT transitions with 35 mutations (87.5%) at the
      middle or 3' guanine. In addition, characteristics of glutathione (GSH)-mediated
      bioactivation were determined for 2ClEMS in vitro. Rates of GSH-mediated
      conjugation, catalyzed by purified rat liver glutathione-S-transferase (GST), and
      binding of [35S]GSH-mediated conjugation products to calf thymus DNA were
      determined for 2ClEMS, 1,2-dichloroethane (EDC) and 1,2-dibromoethane (EDB). The
      relative rates of GSH-mediated conjugation were the following: 5 mM EDB > 40 mM
      2ClEMS > 40 mM EDC. A similar trend was observed for DNA binding of the [35S]GSH
      mediated conjugation products when differences in mutagen concentration were
      considered: EDB > 2ClEMS > EDC. The ratios of DNA binding to GSH conjugation
      calculated for EDB, EDC and 2ClEMS were 6.8 x 10(-5), 9.3 x 10(-5) and 19.1 x 10(
      5), respectively. A narrow range, less than a 3-fold difference, in the ratios of
      DNA binding to GSH conjugation indicates that the bioactivation of 2ClEMS is
      mediated by the same mechanism as EDB and EDC. Consequently, 2ClEMS, EDC and EDB
      may induce a specific mutation in premeiotic germ cells.

PMID- 7500982
TI  - Sister chromatid exchanges (SCEs) and high frequency cells (HFCs) in human
      population studies: principles of their analysis.

PMID- 7500983
TI  - Rodent mutation assay data presentation and statistical assessment.

PMID- 7500984
TI  - Simultaneous evaluation of dexamethasone-induced apoptosis and micronuclei in rat
      primary spleen cell cultures.
AB  - Apoptosis or programmed cell death is a biological event that is biochemically
      and morphologically distinct from cellular necrosis. Nonetheless, its
      relationship has not been studied in terms of a cytogenetic endpoint such as
      micronucleus formation. In the present study, based on cytological observations,
      the incidence of dexamethasone-induced apoptotic cells was related to the
      frequency of micronucleated cells in vitro. Rat primary spleen cells were grown
      in 6-well plates with RPMI 1640 media using concanavalin A and lipopolysaccharide
      as mitogens. At culture initiation, the test agent dexamethasone (10, 20 or 40
      microM) and a cytokinesis inhibitor cytochalasin B (3 micrograms/ml) were added.
      Cultures were harvested 18 h and 40 h later. Slides were prepared and stained
      with Diff-Quik stain. Frequencies of apoptotic cells and micronucleated
      binucleate cells were enumerated cytologically based on 500 cells per treatment
      from the same slides. The results showed a dose-dependent increase in the number
      of apoptotic cells in rat spleen cultures treated with dexamethasone. At 18 h,
      the percentages of apoptotic cells were 0.8, 1.6, 3.4 and 4.4 with 0, 10, 20 and
      40 microM dexamethasone, respectively. The corresponding percentages of apoptotic
      cells at 40 h were: 2.8, 2.6, 5.6 and 10.4. However, at the same concentrations
      of dexamethasone, the micronucleus frequency in binucleate cells remained
      relatively unchanged. The phenomenon of apoptosis induced by dexamethasone was
      confirmed biochemically based on a characteristic DNA 'ladder' pattern by gel
      electrophoresis. These data suggest that dexamethasone at the concentrations
      which induced apoptosis did not produce cytogenetic damage. Also, these findings
      indicate that micronucleus formation and nuclear changes leading to apoptosis are
      separate events and these endpoints may not be closely correlated for
      dexamethasone.

PMID- 7500986
TI  - The rodent dominant lethal assay: regulatory questions concerning appraisal of an
      industrial chemical as exemplified by 1,3-butadiene.
AB  - Ashby has recently described a clear diagrammatic model for the presentation and
      assessment of test data from dominant lethal tests. From a regulatory
      perspective, this approach has the merit of providing data in a standard format.
      Having recently evaluated the dominant lethal test data for butadiene, we have
      identified several areas for consideration and discussion.

PMID- 7500987
TI  - Genetic effects of petroleum fuels: cytogenetic monitoring of gasoline station
      attendants.
AB  - Workers in the petroleum distribution trades experience relatively high-level
      exposures to fuel vapours whose consequences have not been fully elucidated. In
      this study, the possible relationship between occupational exposure to petroleum
      fuels and cytogenetic damages in peripheral lymphocytes was investigated. Twenty
      three male, non-smoking workers from the area of Rome were enrolled in the study,
      together with age-paired controls with no occupational exposure to fuels.
      Peripheral lymphocyte cultures were set up for the analysis of structural
      chromosome aberrations (CAs), sister chromatid exchanges (SCEs) and micronuclei
      (MN) in cytokinesis-blocked lymphocytes. Frequencies of CAs, SCEs and MN were
      compared between exposed and control groups, and evaluated in relation to blood
      lead level (as an indicator of engine exhausts exposure) for the whole group
      under study, and to yearly averaged exposure to benzene (8-h time weighted
      averages, as determined by repeated personal sampling) for fillingstation
      attendants only. Both CAs and SCEs were slightly increased in station attendants:
      1.97 versus 1.46 aberrations per 100 cells, and 4.73 +/- 0.15 versus 4.48 +/-
      0.11 SCEs/cell in exposed and control individuals, respectively. The difference
      between cumulative CA rates in the exposed and control populations was of
      borderline statistical significance (p = 0.066). However, when the exposed
      population was dichotomized for benzene exposure, a significant (p = 0.018)
      correlation of CAs with benzene exposure was found. The analysis of SCE data
      highlighted a significant increase of cells with more than 6 exchanges (HFCs),
      corresponding to the 75 degrees percentile of the overall distribution, in
      fillingstation attendants (relative risk (RR) = 1.3, 95% CI = 1.1-1.5) in
      comparison with controls. In the pooled population, the frequency of HFCs showed
      a statistically significant upward trend at increasing blood lead levels (chi 2
      for trend = 27.8, p < 0.0001). A complex relationship between SCEs and benzene
      exposure was observed, with an increased frequency of HFCs in the medium exposure
      intensity class (RR = 1.5, 95% CI = 1.2-1.7), and no difference for exposure to
      higher benzene levels (RR = 1.0, 95% CI = 0.9-1.2), compared to reference
      subjects. Finally, the analysis of MN in both phytohemagglutinin- and pokeweed
      stimulated cell cultures did not show significant excess of MN in binucleated
      lymphocytes of exposed workers with respect to the age-paired controls.

PMID- 7500985
TI  - Mutant frequency at the hprt locus in human lymphocytes in a case-control study
      of lung cancer.
AB  - A clonal assay to determine the mutant frequency (MF) at the hypoxanthine-guanine
      phosphoribosyl transferase (hprt) locus in human lymphocytes has been used by a
      number of investigators to study exposure to mutagens and carcinogens in a
      variety of populations. We have studied hprt MF in 106 subjects (40 controls and
      66 cases) enrolled in a case-control investigation of lung cancer.
      Epidemiological data collected included smoking history, intake of dietary
      micronutrients, and occupational and environmental exposures as well as medical
      history, all obtained from an interviewer-administered questionnaire. All
      subjects were also genotyped for the known polymorphism in glutathione S
      transferase class mu (GST-mu). In analysis of cases and controls, hprt MF was not
      associated with age, smoking, the polymorphism in GST mu, dietary intake,
      occupational exposures, family history of cancer or usage of medications. Since
      MF and cloning efficiency (CE) are not independent when CE is low, further
      analysis in cases and controls with a CE greater than or equal to 30% (27 cases
      and 22 controls) was also conducted. In analysis of controls, hprt MF increased
      with age and was inversely associated with intake of folate and vitamins A and C.
      The presence of lung cancer was not associated with hprt MF. Thus, our study
      supports the previous observation that dietary components may affect the MF at
      the hprt locus.

PMID- 7500989
TI  - Do human lymphocytes exposed to the fallout of the Chernobyl accident exhibit an
      adaptive response? 1. Challenge with ionizing radiation.
AB  - Several studies suggest that cells appear to become less susceptible to the
      induction of radiation damage, and in particular of chromosome and chromatid
      aberrations in short-term cultures of human lymphocytes, when a challenge
      exposure to ionizing radiation is preceded by a low 'adaptive' dose.
      Contradictory results have been reported on the conditions under which the
      phenomenon can be evidenced. In the present work, circulating lymphocytes of 13
      children contaminated from the fallout after the Chernobyl accident were tested
      for their capability to exhibit an adaptive response in experiments in which the
      challenge dose was administered to stimulated lymphocytes in the S-G2 phase.
      Furthermore, the possible influence of 3-aminobenzamide, an inhibitor of poly(ADP
      ribose) polymerase, was also investigated. Our results indicate that, at least in
      the instance of the end-point here used (chromosome and chromatid aberrations,
      the former resulting possibly from the Cs burden), human lymphocytes, chronically
      exposed to low doses from fallout, do not exhibit any decreased susceptibility to
      ionizing radiation. However, as reported in the accompanying paper, the same
      samples appear to show an 'adaptive' response when exposed to a challenge
      treatment with bleomycin (B. Tedeschi et al., 1995, this issue).

PMID- 7500988
TI  - Evidence of chromosomal instability in the lymphocytes of Gorlin basal-cell
      carcinoma patients.
AB  - The Gorlin syndrome, or naevoid basal-cell carcinoma syndrome (NBCS) is an
      autosomal dominant disease. It has been suspected for long that this cancer prone
      disease (multiple basal-cell carcinomas; other malignant or benign
      proliferations) is a chromosome instability syndrome. We previously reported a
      lengthening in the cell cycle of lymphocytes from two patients with NBCS. With a
      larger sample (n = 7), we confirm this disease to be a chromosome instability
      syndrome, although clearly, expression of this characteristic can vary between
      patients: (1) spontaneous chromatid breaks occurred more often in a subset of the
      patients; (2) spontaneous micronuclei were found more frequently in NBCS than in
      the controls; (3) we confirm the cell cycle to be affected in this disease. As
      these results were obtained on lymphocytes--a cell lineage not affected in NBCS
      manifestations--the chromosome instability we found would appear to be part of
      the general condition of this syndrome.

PMID- 7500990
TI  - Do human lymphocytes exposed to the fallout of the Chernobyl accident exhibit an
      adaptive response? 2. Challenge with bleomycin.
AB  - The present study concerns the possible adaptive response, induced in vivo by a
      continuous exposure to ionizing radiations, to a challenge treatment with the
      radiomimetic glycopeptide bleomycin (BLM). Lymphocytes from children contaminated
      as a consequence of Chernobyl accident were treated for the last 5 h of culture
      with 2.5 micrograms/ml BLM. The induced chromosome damage was significantly lower
      than that found with the same treatment in lymphocytes from control children.
      This hyposensitivity to BLM was still present if, 1 h after the addition of the
      drug, inhibitors of the enzymes involved in DNA repair, such as 3-aminobenzamide
      (2 mM), or aphidicolin (0.4 microM) or 3-dideoxythymidine (5 mM) were added to
      the cultures. The resistance to BLM in lymphocytes from contaminated children
      seems to be related to a mechanism upstream in respect to the activities of
      enzymes involved in the DNA repair and specifically linked to the action of this
      drug. This is consistent with the different response found when the cells were
      challenged with ionizing radiation in vitro, as reported in the accompanying
      paper (L. Padovani, L. et al. (1995) Mutation Res., this issue).

PMID- 7500991
TI  - Quantitative and qualitative aspects of spontaneous specific-locus mutation in
      the ad-3 region of heterokaryon 12 of Neurospora crassa.
AB  - The data from forward-mutation experiments to obtain specific-locus mutations at
      2 closely linked loci in the adenine-3 (ad-3) region of heterokaryon 12 (H-12) of
      Neurospora crassa have been tabulated to determine the frequency of spontaneous
      ad-3 mutations and to determine the percentages resulting from each of the 2
      major genotypic classes: gene/point mutations and multilocus deletion mutations.
      Gene/point mutations at the ad-3B locus (ad-3BR) have been characterized to
      determine the percentage showing allelic complementation to obtain a presumptive
      identification of the genetic alteration in each mutation at the molecular level.
      Data from experiments performed at 2 different laboratories have been compared to
      assess the interlaboratory reproducibility of quantitative data on H-12. No
      difference was found between the frequencies of spontaneous specific-locus
      mutations in the ad-3 region. Genetic analysis of 172 ad-3 mutants demonstrated
      that specific-locus mutations in the ad-3 region result from both gene/point
      mutations (82.0% [141/172]), and multilocus deletion mutations (14.5% [25/172]).
      Heterokaryon tests for allelic complementation demonstrated that 52.5% (53/101)
      spontaneous ad-3BR mutants show allelic complementation, and result from single
      base-pair alterations. In addition, 100% (25/25) of the spontaneous multilocus
      deletion mutations result from the 3 smallest sized genotypic subclasses. The
      implications of the present experimental data for the validation of the ad-3
      specific-locus assay system in Neurospora are discussed.

PMID- 7500992
TI  - Differences in basal and induced DNA single-strand breaks between human
      peripheral monocytes and lymphocytes.
AB  - The aim of this study was to compare the susceptibility of peripheral monocytes
      and lymphocytes to oxidant-induced DNA single-strand breaks (SSB). DNA damage was
      assessed by the alkaline single-cell gel electrophoresis (SCGE) assay. Total
      peripheral mononuclear leukocytes (PML), PML enriched in lymphocytes and PML
      enriched in monocytes were used. The basal rate of SSB was measured after in
      vitro incubation of cells for 1 h in phosphate-buffered saline, and the induced
      rate after incubation in 10 microM or 50 microM H2O2. Incubation was performed at
      4 degrees C to limit the possible influence of DNA repair. Lymphocyte-enriched
      PML were obtained after adhesion of the monocytes to tissue-culture treated
      plastic, and monocyte-enriched PML by removal of monocytes from the plastic
      through trypsin. In all samples, cell differentiation was performed using an
      immunofluorescence technique with antibodies against T- and B-lymphocytes and
      cytospin preparations. The rate of SSB was determined by visual scoring according
      to 6 predefined categories of DNA damage and was expressed as mean score (range 0
      500) per 100 cells. There was a linear relationship between the percentage of
      lymphocytes in the samples and the basal rate of SSB (p < 0.001, slope 0.67 score
      units per %). The same was true for induced DNA damage after incubation in 10
      microM H2O2 (p < 0.001, slope 3.80 score units per %) or 50 microM H2O2 (p <
      0.001, slope 3.22 score units per %). These regression analyses revealed a 2.9
      fold greater rate of basal DNA damage in lymphocytes compared to monocytes and an
      11.3-fold greater rate for the damage induced by 10 microM H2O2. We conclude that
      there are marked differences in the rate of basal and induced SSB between
      lymphocytes and monocytes, suggesting differences in antioxidant capacity between
      the two cell populations. These findings indicate that the assessment of SSB for
      biomonitoring and genotoxicity testing using PML has to take into account
      possible changes in cellular composition.

PMID- 7500993
TI  - An empirical and theoretical study on mechanisms of mutagenic activity of
      hydrazine compounds.
AB  - Hydrazine compounds are important industrial and laboratory chemicals. Many of
      them are carcinogenic in animal tests. Although the carcinogenicity is well
      established, the results of mutagenicity tests performed on alkylhydrazines vary
      greatly in different studies. In an attempt to clarify the situation we have
      applied Salmonella typhimurium TA102 tests to hydrazine and its mono- and
      dimethyl derivatives. These compounds were also tested by an Escherichia coli DNA
      repair-assay. The results of the repair tests indicate that unsymmetrically
      alkylated hydrazines can cause DNA-lesions which are lethal in repair-deficient
      strains. Finally QSAR (Quantitative Structure Activity Relationships) was used to
      develop a model to describe the genotoxic mechanism of hydrazine compounds,
      taking advantage of the results of previous mutagenicity studies. Energy of the
      lowest unoccupied molecular orbital together with octanol-water partition
      coefficient explains nearly completely the mutagenic activity of alkylated
      hydrazine compounds included in the analysis. The mutagenic activity of
      unsubstituted hydrazine is apparently based on different mechanisms.

PMID- 7500994
TI  - Embryonic death, dwarfism and fetal malformations after irradiation of embryos at
      the zygote stage: studies on two mouse strains.
AB  - Female mice of the BALB/c and CF1 strains were mated and irradiated with various
      doses of X-rays 7 h after presumed fertilization. 18 days later, females were
      killed and their uteri examined for prenatal mortality at the different stages of
      development. Living fetuses were weighed and examined for the presence of
      external malformations. A number of them were also examined for skeletal
      anomalies. Radiation induced mainly a dose-dependent increase of the
      preimplantation loss in the BALB/c strain and of the early postimplantation loss
      in the CF1 strain. Embryos of the BALB/c strain were refractory to the induction
      of teratogenic effects after such preimplantation irradiation. In CF1 mice, the
      frequency of malformed fetuses increased regularly after irradiation, the
      difference with controls being significant for the doses of 10, 50 and 100 cGy.
      Dwarfism occurrence also appeared to be increased by irradiation in this strain,
      although the importance of this effect varied depending on the criterion chosen
      for the assessment of dwarfs. With the definition proposed in the present paper,
      the increase in the frequency of dwarfs paralleled that of malformed fetuses,
      being significant after doses of 50 and 100 cGy. Irradiation did not increase the
      frequency of skeletal anomalies. A careful examination of the various data
      obtained to data led us to conclude that radiation may possibly be teratogenic in
      several mouse strains, when administered as early as during the one-cell stage
      and, to a lesser extent, during the following preimplantation stages. However,
      early prenatal mortality will remain by far the greatest risk associated with an
      exposure to radiation during this period. Moreover, the relativity of the risk of
      abnormality due to such irradiation should be considered in the context of the
      high prevalence of developmental defects spontaneously occurring during human
      pregnancy.

PMID- 7500995
TI  - Molecular analysis of the TK locus in L5178Y large and small colony mouse
      lymphoma cell mutants induced by hycanthone methanesulfonate.
AB  - Mouse lymphoma cells of the L5178Y TK + /-3.7.2C line were exposed to varying
      concentrations of the anti-schistosomal drug hycanthone methanesulfonate. The
      trifluorothymidine (TFT)-resistant cells fell into two classes based on colony
      size. Southern blot analyses were performed using NcoI-digested DNA from a number
      of large and small mutant colonies from each treatment group. Two different
      restriction fragment banding patterns were identified in these analyses, those
      colonies that contained the 6.4 kb NcoI restriction fragment and those that did
      not. A total of 471 mutant colonies were analyzed and 84.5% (398) of these
      colonies did not exhibit the 6.4 kb fragment. There did not appear to be a
      hycanthone methanesulfonate dose response effect in the number of colonies that
      did not contain the 6.4 kb fragment among the treated groups. In addition, 82%
      (154 out of 188) of spontaneous mutants did not contain the 6.4 kb fragment. The
      results imply that greater than 80% of all spontaneous mutations found in the
      mouse lymphoma assay regardless of colony size do not contain the 6.4 kb fragment
      and each may be considered to be a large scale mutation. In addition, greater
      than 80% of the hycanthone induced mutations in the mouse lymphoma assay do not
      contain the 6.4 kb fragment and thus may be considered to be a large scale
      mutation.

PMID- 7500996
TI  - Detection of oxidative mutagens in strains of Escherichia coli deficient in the
      OxyR or MutY functions: dependence on SOS mutagenesis.
AB  - The Escherichia coli strain IC3821, a delta oxyR derivative of WP2 uvrA trpE65,
      was more sensitive to mutagenicity promoted by t-butyl hydroperoxide and cumene
      hydroperoxide than the isogenic oxyR+ control. Mutagenicity of menadione, a redox
      cycling quinone, was clearly detected in the delta oxyR strain, whereas only a
      slight mutagenic response was observed in the oxyR+ strain. Plumbagin, another
      quinone structurally similar to menadione, was not mutagenic to any of the
      strains. These mutagenic responses appeared to involve the SOS processing of
      oxidative DNA lesions and were mediated by MucA/B proteins more efficiently than
      by UmuD/C. In cells lacking mutagenesis proteins, induction of SOS-independent
      mutations by the two alkyl hydroperoxides required a deficiency in the MutY DNA
      glycosylase and was increased by the presence of the delta oxyR mutation. In
      contrast, the two quinones assayed were unable to induce SOS-independent
      mutations in the MutY-deficient strains.

PMID- 7500999
TI  - NASA panel draws up 'road map' to hunt earth-like planets in space.

PMID- 7500997
TI  - Effect of low doses of gamma-radiation on the steady-state spermatogenesis of
      mouse: a flow-cytometric study.
AB  - Radiation-induced perturbations in the steady-state spermatogenesis of mouse
      exposed to 0.05 to 2 Gy of 60Co gamma-radiation were studied at 7 to 70 days post
      irradiation flow cytometrically. Five quantifiable populations viz: elongated
      spermatids (HC), round spermatids (1C), spermatogonia and other diploid cells
      (2C), spermatogonial cells synthesizing DNA (S-phase) and primary spermatocytes
      (4C) were identified in the sham-irradiated controls. Exposure of mice to
      different doses of radiation resulted in a significant decline in the total germ
      cell transformation ratio (1C:2C) at 21 and 28 days post-irradiation as compared
      to the control group, except for the animals exposed to 0.05 Gy. The 1C:2C ratio
      is sub-divided into two components viz. 4C:2C and 1C:4C. The 4C:2C ratio
      decreased significantly on day 14 post-irradiation, except for 0.05 Gy where it
      was non-significant. Consequently, meiotic transformation (1C:4C) showed a
      significant increase on day 14 post-irradiation compared to the sham-irradiated
      control barring 0.05 Gy where the difference between the two groups was non
      significant. The ratio of HC:1C (cell transformation during spermiogenesis)
      increased significantly at day 21 post-irradiation 0.2 to 2 Gy and between day 7
      and 14 for 0.05 Gy as compared to the control group. It appears that a dose as
      low as 0.05 Gy radiation was able to cause the perturbations in the steady-state
      spermatogenesis of mouse and normalcy was not restored even up to 70 days post
      irradiation at all exposure doses.

PMID- 7500998
TI  - Australian institute gets new director.

PMID- 7501000
TI  - Government backs proteome proposal.

PMID- 7501001
TI  - Researchers split over food safety as schools ban beef.

PMID- 7501002
TI  - Funds are key to sequence success.

PMID- 7501003
TI  - Hyping results 'could damage' gene therapy.

PMID- 7501004
TI  - Pain pathways.

PMID- 7501005
TI  - Security at MIT.

PMID- 7501006
TI  - Survival of Italian biomedical research.
AB  - Despite crises in image and funding, Italian biomedical research has reached a
      turning point. A brighter future is in prospect if the universities successfully
      reorganize themselves and new competitive institutes are established.

PMID- 7501007
TI  - Muscle. Hops, steps and jumps.

PMID- 7501008
TI  - Schizophrenia. All out for chromosome six.

PMID- 7501009
TI  - Drug addiction. Cocaine abuse takes a shot.

PMID- 7501010
TI  - Whose baby are you?

PMID- 7501011
TI  - Lifting the Taung child.

PMID- 7501012
TI  - Energetic motion detection.

PMID- 7501013
TI  - Mariner transposons in humans.

PMID- 7501014
TI  - Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans
      retinoic acid.
AB  - The 2.0-A crystal structure of the ligand-binding domain (LBD) of the human
      retinoic acid receptor (RAR)-gamma bound to all-trans retinoic acid reveals the
      ligand-binding interactions and suggests an electrostatic guidance mechanism. The
      overall fold is similar to that of the human RXR-alpha apo-LBD, except for the
      carboxy-terminal part which folds back towards the LBD core, contributing to the
      hydrophobic ligand pocket and 'sealing' its entry site. We propose a 'mouse trap'
      mechanism whereby a ligand-induced conformational transition repositions the
      amphipathic alpha-helix of the AF-2 activating domain and forms a
      transcriptionally active receptor.

PMID- 7501015
TI  - A structural role for hormone in the thyroid hormone receptor.
AB  - The crystal structure of the rat alpha 1 thyroid hormone receptor ligand-binding
      domain bound with a thyroid hormone agonist reveals that ligand is completely
      buried within the domain as part of the hydrophobic core. In addition, the
      carboxy-terminal activation domain forms an amphipathic helix, with its
      hydrophobic face constituting part of the hormone binding cavity. These
      observations suggest a structural role for ligand, in establishing the active
      conformation of the receptor, that is likely to underlie hormonal regulation of
      gene expression for the nuclear receptors.

PMID- 7501016
TI  - A water-vapour giga-maser in the active galaxy TXFS2226-184.
AB  - Active galactic nuclei are thought to be powered by gas falling into a massive
      black hole; the different types of active galaxy may arise because we view them
      through a thick torus of molecular gas at varying angles of inclination. One way
      to determine whether the black hole is surrounded by a torus, which would obscure
      the accretion disk around the black hole along certain lines of sight, is to
      search for water masers, as these exist only in regions with plentiful molecular
      gas. Since the first detection of an extra-galactic water maser in 1979, they
      have come to be associated primarily with active galaxies, and have even been
      used to probe the mass of the central engine. Here we report the detection of a
      water giga-maser in the radio galaxy TXFS2226-184. The strength of the emission
      supports a recently proposed theory of maser pumping that allows for even more
      powerful masers, which might be detectable at cosmological distances. Water
      masers may accordingly provide a way to determine distances to galaxies outside
      the usual distance ladder, providing an independent calibration of the Hubble
      constant.

PMID- 7501017
TI  - Dorsal cell fate specified by chick Lmx1 during vertebrate limb development.
AB  - The positional cues that govern the fate of cells along the dorsoventral axis of
      the developing vertebrate limb are established in the mesoderm before outgrowth
      of limb buds. In Drosophila, a LIM/-homeodomain gene, apterous, expressed in the
      dorsal compartment of the wing disc, specifies dorsal cell fate. Here we report
      the isolation of a vertebrate LIM-homeodomain containing gene, Chick Lmx1 (C
      Lmx1). Transcripts for C-Lmx1 are detected in the presumptive dorsal limb
      mesoderm and are restricted thereafter to the dorsal mesoderm of the developing
      chick bud. C-Lmx1 expression is regulated by the overlying ectoderm where Wnt7a
      messenger RNA is localized. Wnt7a, required for normal development of the
      dorsoventral axis in mouse limbs, can induce ectopic expression of C-Lmx1 in
      ventral mesoderm. Misexpression of C-Lmx1 during limb outgrowth causes ventral to
      dorsal transformations of limb mesoderm. We propose that C-Lmx1 specifies dorsal
      cell fate during chick limb development.

PMID- 7501018
TI  - Chromosome engineering in mice.
AB  - Chromosomal rearrangements are the major cause of inherited human disease and
      fetal loss. Translocations and loss of heterozygosity are important genetic
      changes causally involved in neoplasia. Chromosomal variants, such as
      deficiencies, are commonly exploited in genetic screens in organisms such as
      Drosophila because a small portion of the genome is functionally hemizygous. In
      the mouse, deficiencies are not generally available, thus genetic screens for
      recessive mutations are cumbersome. We report here that defined deficiencies,
      inversions and duplications extending to 3-4 cM can be constructed in embryonic
      stem cells. This was achieved by consecutive targeting of loxP recombination
      substrates to the end points of a genetic interval followed by Cre-induced
      recombination. This reconstructs a positive selectable marker which facilitates
      direct selection of clones with a chromosome structure specific to the relative
      orientation of the loxP sites. Duplication and deletion alleles have been
      transmitted into the mouse germ line. The availability of mice with defined
      regions of segmental haploidy will allow their use in genetic screens and enable
      accurate models of human 'chromosomal' diseases to be generated.

PMID- 7501019
TI  - Essential function of LIF receptor in motor neurons.
AB  - Development and maintenance of the mammalian nervous system is dependent upon
      neurotrophic cytokines. One class of neurotrophic factor acts through receptor
      complexes involving the low-affinity leukaemia inhibitory factor receptor subunit
      (LIF-R). Members of this family of cytokines, such as ciliary neurotrophic factor
      (CNTF) and leukaemia inhibitory factor (LIF), have profound effects on the
      survival and maintenance of motor neurons. Recently it was reported that mice
      lacking LIF-R die shortly after birth unlike mice lacking CNTF or LIF which are
      viable. Here we describe histopathological analyses of lifr mutants that reveal a
      loss > 35% of facial motor neurons, 40% of spinal motor neurons and 50% of
      neurons in the nucleus ambiguus. These findings point to the existence of a
      ligand for LIF-R that is required for the normal development of motor neurons in
      both brainstem nuclei and spinal cord.

PMID- 7501020
TI  - Suppression of psychoactive effects of cocaine by active immunization.
AB  - Cocaine is a powerfully addictive substance and new strategies are needed to
      treat its abuse. Generating an active immunization to cocaine offers a means of
      blocking the actions of the drug by preventing it from entering the central
      nervous system, and should have fewer side effects than treatments based on
      manipulation of central neurotransmitter function. The design and preparation of
      a cocaine immunogen requires special regard for the stability of cocaine both
      free and as a haptenic determinant. Immunochemistry and a well defined
      behavioural model were brought together to address the problem of inactivation of
      the psychostimulant actions of cocaine. We report here that active immunization
      with a new, stable cocaine conjugate suppressed locomotor activity and
      stereotyped behaviour in rats induced by cocaine but not by amphetamine.
      Moreover, following acute injection of cocaine, levels of cocaine in the striatum
      and cerebellum of the immunized animals were lower than those of control animals.
      These results suggest that immunopharmacotherapy may be a promising means by
      which to explore new treatments for cocaine abuse.

PMID- 7501021
TI  - Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel.
AB  - The peptide Phe-Met-Arg-Phe-NH2 (FMRFamide) and structurally related peptides are
      present both in invertebrate and vertebrate nervous systems. Although they
      constitute a major class of invertebrate peptide neurotransmitters, the molecular
      structure of their receptors has not yet been identified. In neurons of the snail
      Helix aspersa, as well as in Aplysia bursting and motor neurons, FMRFamide
      induces a fast excitatory depolarizing response due to direct activation of an
      amiloride-sensitive Na+ channel. We have now isolated a complementary DNA from
      Helix nervous tissue; when expressed in Xenopus oocytes, it encodes an FMRFamide
      activated Na+ channel (FaNaCh) that can be blocked by amiloride. The
      corresponding protein shares a very low sequence identity with the previously
      cloned epithelial Na+ channel subunits and Caenorhabditis elegans degenerins, but
      it displays the same overall structural organization. To our knowledge, this is
      the first characterization of a peptide-gated ionotropic receptor.

PMID- 7501022
TI  - A possible docking and fusion particle for synaptic transmission.
AB  - Several proteins have been implicated in the rapid (millisecond) calcium
      controlled release of transmitters at nerve endings, including soluble N
      ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein
      (alpha-SNAP), the synaptic SNAP receptor (SNARE) and the calcium-binding protein
      synaptotagmin, which may function as a calcium sensor in exocytosis. A second
      SNAP isoform (beta-SNAP), which is 83% identical to alpha-SNAP, is highly
      expressed in brain, but its role is still unclear. Here we show that these
      proteins assemble cooperatively to form a docking and fusion complex. beta-SNAP
      (but not alpha-SNAP) binds synaptotagmin and recruits NSF, indicating that the
      complex may link the process of membrane fusion to calcium entry by attaching a
      specialized fusion protein (beta-SNAP) to a calcium sensor (synaptotagmin).
      Polyphosphoinositols that block transmitter release, inositol 1,3,4,5
      tetrakisphosphate (InsP4), inositol 1,3,4,5,6-pentakisphosphate (InsP5) and
      inositol 1,2,3,4,5,6-hexakisphosphate (InsP6), also block the assembly of the
      particle by preventing beta-SNAP from binding to synaptotagmin.

PMID- 7501023
TI  - Apoptosis of T cells mediated by galectin-1.
AB  - Galectin-1, a member of the family of beta-galactoside binding proteins, has
      growth regulatory and immunomodulatory activities. We report here that galectin
      1, expressed by stromal cells in human thymus and lymph nodes, is present at
      sites of cell death by apoptosis during normal T-cell development and maturation.
      Galectin-1 induced apoptosis of activated human T cells and human T leukaemia
      cell lines. Resting T cells also bound galectin-1, but did not undergo apoptosis.
      Human endothelial cells that expressed galectin-1 induced apoptosis of bound T
      cells. Galectin-1-induced apoptosis required expression of CD45, and was
      decreased when N-glycan elongation was blocked by treatment of the cells by
      swainsonine, whereas inhibition of O-glycan elongation potentiated the apoptotic
      effect of galectin-1. Induction of apoptosis by an endogenous mammalian lectin
      represents a new mechanism for regulating the immune response.

PMID- 7501024
TI  - Cell-cycle control linked to extracellular environment by MAP kinase pathway in
      fission yeast.
AB  - In fission yeast the onset of mitosis is brought about by Cdc2/Cdc13 kinase,
      which is inhibited by the Wee1/Mik1 tyrosine kinases and activated by Cdc25
      tyrosine phosphatase. This control network integrates many signals, including
      those that monitor DNA replication, DNA damage and cell size. We report here that
      a fission yeast MAP kinase pathway links the cell-cycle G2/M control with changes
      in the extracellular environment that affect cell physiology. Fission yeast spc1-
      mutants have a G2 delay that is greatly exacerbated by growth in high osmolarity
      media and nutrient limitation. A lethal interaction of spc1 and cdc25 mutations
      shows that Spc1 promotes the onset of mitosis. Spc1 is a MAP kinase homologue
      that is activated by Wis1 kinase in response to osmotic stress and nutrient
      limitation. Spc1 is inactivated by Pyp1, a phosphatase previously identified as a
      mitotic inhibitor. Pyp1 dephosphorylates only tyrosine-173 of Spc1, unlike the
      dual-specificity phosphatases that have been shown to regulate other MAP kinases.

PMID- 7501025
TI  - Crystal structure of SIV matrix antigen and implications for virus assembly.
AB  - Simian immunodeficiency virus (SIV) is closely related to human immunodeficiency
      virus (HIV), their matrix antigens (MAs) sharing some 50% sequence identity. MA
      is a component of Pr55Gag, the sole protein required for assembly of the virion
      shell. MA targets Pr55 to the plasma membrane, and facilitates incorporation of
      the virus envelope protein and assembly of the Pr55Gag shell. Cleavage of Pr55 by
      the viral protease produces the mature protein of relative molecular mass 17-18K,
      which underlies the host-derived membrane and is important in both virus entry
      and nuclear localization of the virion core. Here we report the crystal structure
      of SIV MA. The molecule forms a trimer consistent with oligomerization in vitro,
      the observed virion architecture, and various biological properties of MA.

PMID- 7501026
TI  - A 35-A movement of smooth muscle myosin on ADP release.
AB  - Myosin II crossbridges interact with F-actin producing powerstrokes of around 100
      A (refs 1, 2), during which the products of ATP hydrolysis are released. This has
      been postulated to involve an articulation of the myosin head (S1) on actin, or
      substantial conformational changes in S1 itself. Small movements of the
      regulatory light chain have been detected (see, for example, refs 9, 10), but
      most data suggest that the bulk of S1 does not move on actin during crossbridge
      cycling. Here we present three-dimensional maps of S1-decorated F-actin in the
      presence and absence of MgADP. The myosin motor domain is similar in both states
      but there are major orientational differences in the light-chain-binding domain.
      This domain acts as a rigid level arm pivoting about the end of the motor domain
      and swinging approximately 23 degrees, resulting in a approximately 35-A step.
      Small, nucleotide-mediated conformational changes in the motor domain may thus be
      converted by the light-chain domain into large movement steps.

PMID- 7501027
TI  - A 32 degree tail swing in brush border myosin I on ADP release.
AB  - Brush border myosin I (BBMI) is a single-headed, unconventional myosin from
      intestinal microvilli, composed of a heavy chain of relative molecular mass
      119,000 (M(r) 119K) and three calmodulin light chains. Although believed to have
      a largely structural role, it exhibits the normal actin-activated ATPase and
      motility properties of a member of the myosin superfamily. Here we present three
      dimensional maps of BBMI-decorated actin filaments with and without bound MgADP.
      While the motor domain remains in a state similar to rigor, the light-chain
      binding domain swings through approximately 32 degrees, resulting in a
      approximately 50-A movement at the end of the region visualized (the second
      calmodulin light chain). This could correspond to approximately 72-A movement of
      the entire domain. Although qualitatively similar to the movement observed in
      myosin II, the magnitude of the change is sufficiently different to suggest that
      structural changes during the actomyosin ATPase cycle differ among myosins,
      possibly reflecting adaptation for specialized functional demands.

PMID- 7501029
TI  - Kaiser sets new standards for ESRD contractors.

PMID- 7501028
TI  - Percentage of deaths drops despite steady growth in ESRD population.

PMID- 7501030
TI  - Indian government tries to curb illicit organ trade.

PMID- 7501031
TI  - Dialysis during war-time. Part II. Croatians fill dialysis units, await
      transplants.

PMID- 7501032
TI  - The RAND Kidney Disease and Quality of Life instrument.

PMID- 7501034
TI  - Minorities and ESRD. Part I. Tracking the causes of ESRD in the Hispanic
      population.

PMID- 7501033
TI  - The challenges facing minorities: an overview.

PMID- 7501035
TI  - Hispanic renal nutrition. Nuances of the Mexican-American renal diet.

PMID- 7501036
TI  - Taking a closer look at employee turnover in the dialysis unit.

PMID- 7501037
TI  - Staff turnover in the dialysis unit. Interview by Diane Boudreau.

PMID- 7501038
TI  - [Freud and hysteria. Significance of the (early) psychoanalytic viewpoint for
      current psychotherapy].

PMID- 7501039
TI  - [Freud and hysteria: 1895-1995].

PMID- 7501040
TI  - [Hysteria since Sigmund Freud].

PMID- 7501041
TI  - [Freud, Charcot and the neurological viewpoint of hysteria].

PMID- 7501042
TI  - [Pierre Janet and Sigmund Freud on hysteria, trauma and dissociation].

PMID- 7501043
TI  - [Freud and psychiatry about 1900].

PMID- 7501044
TI  - [Freud, fraud and repression].

PMID- 7501045
TI  - [Hysteria in the Dutch novel of the turn of the century].

PMID- 7501046
TI  - [Biography and psychoanalysis; searching for Frederik van Eeden's character].

PMID- 7501047
TI  - [Metastases from unknown primary tumor].

PMID- 7501048
TI  - [HIV infection in hemophilia patients; report from the National Ombudsman].

PMID- 7501049
TI  - ['Stomach-friendly' NSAIDs: careful optimism?].

PMID- 7501050
TI  - [Indications for antineoplastic effects of nonsteroidal anti-inflammatory drugs].

PMID- 7501051
TI  - [Pathogenesis of tumor metastases].

PMID- 7501052
TI  - [Determination of spectrin in erythrocytes: an important aid in the diagnosis of
      hereditary spherocytosis].
AB  - OBJECTIVE: Assay of spectrin in erythrocytes as a diagnostic test in hereditary
      spherocytosis (HS). DESIGN: Validation of a diagnostic test. SETTING: Central
      Laboratory of the Netherlands Red Cross Blood Transfusion Service in Amsterdam,
      the Netherlands. METHOD: A radiolabelled rabbit antiserum against human spectrin
      was used to determine the amount of spectrin in erythrocytes from 64 patients
      with proven or supposed HS, suffering from inborn, sometimes familial anaemia and
      a decreased osmotic resistance of the erythrocytes. These amounts of spectrin
      were compared with those of 12 patients with decreased osmotic resistance
      suffering from haemolytic anaemia of unknown cause, 16 patients with various
      other erythrocyte disorders and 30 healthy blood donors. RESULTS: The intradonor
      and interdonor variations in the amount of spectrin in erythrocytes from healthy
      blood donors were found to be less than 7%. In 56 of the 64 patients with HS
      (88%), the erythrocytes contained less than 86% of the normal amount of spectrin.
      A similar result was found in 4 of the 12 patients suffering from non
      characterised haemolytic anaemia (33%). In contrast, a normal amount of spectrin
      was found in the erythrocytes of patients with other erythrocytic disorders.
      CONCLUSION: The radio-immunoassay of spectrin in erythrocytes is more specific
      for the diagnosis of HS than the osmotic fragility test of the erythrocytes. The
      normal amount of spectrin found in 8 of the 64 patients possibly suffering from
      HS may be due to a rare molecular origin of HS not leading to a decreased
      spectrin level or may be related to other causes of anaemia than HS.

PMID- 7501053
TI  - [Ascites, hydrothorax and ovarian tumor: Meigs' syndrome in a patient with small
      ovaries and increased CA 125 level].
AB  - In a 51-year-old woman with bilateral Brenner tumours of the ovaries and with
      intermittent hydrothorax and ascites, Meigs' syndrome was diagnosed. The serum CA
      125 level was 620 U/ml (normal: 5-35). Bilateral ovariectomy, hysterectomy and
      omentectomy were carried out. The ovaries were not enlarged. Postoperatively, the
      pleural effusion and ascites resolved and the CA 125 level decreased to 8.4 U/ml.
      The pathogenesis of hydrothorax probably involves passage through the diaphragm,
      and the CA 125 may be produced by the peritoneal lining or by the Brenner
      tumours.

PMID- 7501054
TI  - [Generalized side effects with the use of carbamazepine].
AB  - Since 1973, 42 cases of generalized adverse reactions to carbamazepine were
      reported to the Netherlands Centre for Monitoring of Adverse Reactions to Drugs
      and the Belgian Centre for Drug Monitoring. The organ involvement can be very
      diverse in an allergic reaction to carbamazepine. Serious and protracted
      disturbances in pulmonary diffusion capacity may be present even in the absence
      of changes on the chest X-ray. Analysis of the type IV mechanism involved
      suggests that caution is warranted with regard to administration of other drugs
      during the acute phase of the allergic reaction particularly if these drugs have
      a propensity to cause type IV allergic reactions themselves.

PMID- 7501055
TI  - [From the library of the Nederlands Tijdschrift voor Geneeskunde: Medical
      Electricity: therapeutic application of an 18th-century invention].

PMID- 7501056
TI  - [Satisfactory surgical results in elderly patients with stage I lung carcinoma;].

PMID- 7501057
TI  - [Problems in the interpretation of the percentage of glycosylated hemoglobin in
      patients with diabetes mellitus].

PMID- 7501058
TI  - [Of mice and men: pathogenesis and treatment of obesity in genetic perspective].

PMID- 7501059
TI  - [Pharmacotherapy between theory and practice].

PMID- 7501060
TI  - [Vascular disorders following chemotherapy].

PMID- 7501061
TI  - [Vesico-ureteral reflux; causes, diagnosis and treatment].

PMID- 7501062
TI  - [20-year national screening for phenylketonuria in The Netherlands. National
      Guidance Commission PKU].
AB  - OBJECTIVE: Evaluation of the Dutch national screening programme for
      phenylketonuria (PKU). DESIGN: Descriptive. SETTING: Nationwide. METHODS: Data on
      the screening were obtained from the laboratories, from the registration offices
      of vaccination and screening results and from the paediatricians to whom infants
      with positive screening values were referred, during the period from September
      1st, 1974 to December 31st, 1993. RESULTS: During the study period 3,481,738
      infants were screened in the Netherlands (99.4% of all live births). The
      sensitivity of the programme was 98%, the specificity 99.99% and the positive
      predictive value 50%. The prevalence of PKU varied considerably between regions,
      e.g. from 1:33,600 in Zuid-Holland to 1:8,250 in Limburg (average in the
      Netherlands 1:18,000). The percentage of patients treated before the age of 22
      days was 84% in the period from 1974 to 1988 and 95% in the period from 1989 to
      1993 (p = 0.04). Birth weight in patients with PKU was 141 g (95% confidence
      interval: 66-216) less than the expected birth weight in the Netherlands.
      Furthermore, a slight growth retardation occurred in the first three years of
      life in early treated patients. The percentage of patients following special
      education was twice as high as in the general population (p < 0.001). CONCLUSION:
      The screening procedure for PKU is functioning at a high level. Despite early
      treatment development of patients with PKU is slightly below normal.

PMID- 7501063
TI  - [Reasons to report or not report side effects of drugs to the national monitoring
      system in the Netherlands].
AB  - OBJECTIVE: To assess the awareness of medical practitioners in the Netherlands
      regarding the national voluntary reporting scheme for adverse reactions to drugs,
      and the reasons for non-reporting. DESIGN: Questionnaire. SETTING: Netherlands
      Centre for Monitoring of Adverse Reactions to Drugs. METHOD: A questionnaire was
      sent to a random sample of 500 practitioners aged under 65 in the database of the
      Dutch Inspectorate for Health Care. RESULTS: Of the 500 questionnaires 265 (53%)
      were returned and completely filled in. Sixty-seven (25%) practitioners had
      reported a suspected adverse reaction on one or several occasions during their
      practising career; 229 (86%) would report a serious adverse reaction, 190 (72%)
      an unknown one, 185 (70%) an adverse reaction to a new product, and 83 (31%) a
      proven adverse reaction. Almost 20% said they had had difficulties reporting
      because they could not find the telephone number or reporting forms. Forty
      practitioners (15%) claimed that they were too busy to report adverse reactions.
      Almost all practitioners (94%) were aware of the fact that the reporting scheme
      serves the early detection of unknown adverse reactions.

PMID- 7501064
TI  - [Decrease in coronary heart disease mortality in 1974-1992 largely explainable by
      changes in cholesterol and smoking risk factors].
AB  - OBJECTIVE: To ascertain to what extent the dramatic decrease in coronary heart
      disease (CHD) mortality from 1972 to the present can be attributed to a change in
      risk factors. DESIGN: Descriptive study based on literature data. SETTING: The
      Netherlands. METHODS: Changes in four risk factors were assessed: a survey on
      trends in average systolic and diastolic blood pressure and serum cholesterol
      from three national screening projects, conducted 1974-1980, among 30,000 men and
      women aged 37-43 years, 1981-1986 among 80,000 men aged 33-37 years, and 1987
      1992 among 42,000 men and women aged 20-59 years, and the percentage of smokers
      observed by the Foundation on Public Health and Smoking in yearly surveys among
      20,000 people from the age of 15. Using a preventable proportion calculation, the
      effect on mortality was estimated of the observed changes in these risk factors,
      applying published relative risks and regression coefficients for these risk
      factors for men. The estimated curves were compared with the coronary mortality
      curves observed by the Netherlands Central Bureau of Statistics. RESULTS: From
      1974 to 1992 a substantial decrease in the percentage of smokers and in men a
      moderate decrease in average serum cholesterol level were observed. Serum
      cholesterol decreased little in women. Changes in blood pressure were not
      consistent. The calculations predicted a 33% decrease in CHD mortality; the
      decrease actually observed was 48% for men aged 20-69 and 42% for women.
      CONCLUSION: It appears that by far the largest proportion of the decrease in CHD
      mortality can be explained by a decrease in the values of relevant risk factors
      (cholesterol and smoking) and only a small part by improved therapy.

PMID- 7501065
TI  - [Gentamicin skin ointment: 200 kilos too much].
AB  - In a 75 year old woman, with diabetic mellitus type II, bacteriological
      examination of a foot infection revealed a Staphylococcus aureus resistant to
      aminoglycosides. From a different ulcer on the same foot a genotypically
      identical but non-resistant bacterial strain was cultured. The patient had been
      treated with gentamicin ointment. According to the literature and to the Central
      Pharmaceutical Committee in the Netherlands there is no indication for topical
      use of gentamicin or other aminoglycosides. Moreover, such use may lead to
      antibiotic resistant bacteria. In spite of this, in the period from March 1992 to
      March 1993, 200 kg of the ointment was distributed in the Netherlands.

PMID- 7501066
TI  - [Vaccination against influenza superfluous in patients with (recurrent)
      staphylococcal infections].

PMID- 7501067
TI  - [Progress assessment of medical competence as a (national) physicians'
      examination?].

PMID- 7501069
TI  - [Systematic approach to a difficult diagnostic problem].

PMID- 7501068
TI  - [Primary health care in Ghana: no pay no cure?].

PMID- 7501070
TI  - [100 years of radiology in The Netherlands].

PMID- 7501071
TI  - [Cystic fibrosis and Burkholderia (formerly Pseudomonas) cepacia: an increasing
      clinical and psychosocial problem].

PMID- 7501072
TI  - [Pathogenesis and diagnosis of bacterial airway infections in patients with
      cystic fibrosis].

PMID- 7501074
TI  - [100 years of radiology in The Netherlands. I. Radiodiagnosis, current status].

PMID- 7501073
TI  - [Prevention and therapy of airway infections in patients with cystic fibrosis].

PMID- 7501075
TI  - [100 years of radiology in The Netherlands. II. Radiodiagnosis, future
      developments].

PMID- 7501077
TI  - [Results of photorefractive keratectomy using the excimer laser in the treatment
      of myopia; 1-year follow-up].
AB  - OBJECTIVE: Evaluation of the first excimer laser treatments of myopia. DESIGN:
      Descriptive. SETTING: Excimer Laser Centrum, Department of Ophthalmology,
      University of Nijmegen, Nijmegen, the Netherlands. METHOD: 312 patients underwent
      spherical excimer laser treatment to correct myopia of 1.2 up to 10 diopters
      between February 1992 and October 1993. 245 patients completed a follow-up of one
      year or more; 36 retreatments were carried out. Group I (treatment 1.2 to 6 D)
      numbered 174 patients, group II (6.1-10 D) 71 patients. RESULTS: After a follow
      up period of one year or just before retreatment 79% of group I and 48% of group
      II achieved a refractive correction within 1 D of the attempted correction.
      Visual acuity without correction was 0.5 or more in 94% of group I and in 76% of
      group II. Less than one percent (n = 1) of group I and 6% (n = 4) of group II
      lost more than one line of best corrected visual acuity. Retreatment could
      correct 50% of those eyes that did not achieve a refraction within 1 D of
      attempted correction. Loss of visual acuity was corrected by retreatment in 5 of
      6 cases of group I and in 7 of 11 cases of group II. CONCLUSION: Based on a one
      year follow-up, refractive surgery with the excimer laser appears to correct
      myopia between 1 and 10 D effectively. Predictability is diminishing on
      correcting higher amounts of refractive error. Thorough information of the
      patients regarding the results to be expected will prevent disappointment.

PMID- 7501076
TI  - [What to do in a 60-year-old HIV-positive woman with a cerebral arteriovenous
      malformation? Decision analysis].
AB  - OBJECTIVE: To illustrate how clinical decision analysis can contribute to modern
      medical practice. DESIGN: Clinical decision analysis. SETTING: Academic Hospital
      Rotterdam-Dijkzigt, Rotterdam, the Netherlands. METHOD: Three treatment options
      (no treatment, neurosurgery and radiosurgery) for a 60-year-old HIV-positive
      woman with a once-ruptured cerebral arteriovenous malformation were compared
      using clinical decision analysis, with respect to the discounted quality adjusted
      life expectancy. Estimates of the risk of bleeding and its complications, of the
      efficacy and complications of treatment, and of the risk of developing AIDS and
      its consequences were based on the clinical literature. RESULTS: Differences
      between no treatment and neurosurgery or radiosurgery amounted to 0.1 (plausible
      range: -0.27 to 0.84) and 0.2 (plausible range: -0.29 to 0.76) discounted quality
      adjusted life years, in favour of no treatment. The limited life expectancy of
      the patient, leading to a relatively low cumulative risk of haemorrhage, did not
      appear to justify the risks of treatment. CONCLUSION: Clinical decision
      consultation may provide a rational, thorough and explicit decision procedure
      which takes into account the complexity of medical care.

PMID- 7501078
TI  - [Transient erythroblastopenia in 4 children].
AB  - In four patients, all girls, aged 2, 3.5, 4 and 5 years, transient
      erythroblastopenia was diagnosed. The children were presented because of acute
      pallor. The haemoglobin levels were 2.8 to 5.0 mmol/l. After 3 weeks all patients
      had recovered or were recovering with increasing haemoglobin values. Three of the
      four patients needed one blood transfusion. In two patients there was evidence of
      a parvovirus B19 infection. Transient erythroblastopenia is mostly seen in
      patients aged 1-4 years. Most cases are postinfectious and there is evidence that
      human parvovirus B19 is responsible for many cases. In the very young child the
      differential diagnosis from Blackfan-Diamond anaemia may be very difficult.

PMID- 7501079
TI  - [Liver damage attributed to the use of disulfiram].
AB  - In three alcoholic patients, two men aged 30 and 42, and a woman aged 52,
      hepatitis was diagnosed after the use of disulfiram. In all cases, there was a
      close temporal relationship between the occurrence of symptoms and disulfiram
      intake. Other possible causes were excluded. The 30-year-old man died from liver
      damage. Biopsy showed massive hepatic necrosis without signs of alcoholic
      hepatitis. In the other patients, symptoms subsided quickly and liver function
      returned to normal after discontinuation of disulfiram, but there was no
      confirmation by biopsy. The possibility of drug-induced hepatitis should always
      be considered in an alcoholic patient treated with disulfiram.

PMID- 7501080
TI  - [100 years of radiology in The Netherlands. III. Radiodiagnosis, a historical
      overview].

PMID- 7501081
TI  - [How should ear wax be removed?].

PMID- 7501082
TI  - [When are bronchodilator agents sufficient in asthma/chronic obstructive lung
      disease?].

PMID- 7501083
TI  - [Pathophysiology of perinatal asphyxia and brain damage].

PMID- 7501084
TI  - [Progressive supranuclear paralysis; a late diagnosis].

PMID- 7501085
TI  - [Increase in risk of endometrial carcinoma following treatment of breast
      carcinoma with tamoxifen].

PMID- 7501086
TI  - [Treatment of patients with trophoblastic tumor in the Academic Medical Center:
      31 patients in 10 years, 1983-1992].

PMID- 7501087
TI  - [Recommendations for the diagnosis and therapy of insomnia. German Society of
      Sleep Research and Sleep Medicine DGSM].
AB  - There exist a variety of American and European recommendations regarding
      treatment with hypnotics, especially the duration of treatment. The German Sleep
      Society now publishes its own view to help physicians to cope with these
      different recommendations, some of which are contradictory. Therapy with
      hypnotics must include substantial information on the type of drug, dose, timing
      and duration as well as information about the possibility of interval treatment.
      Agonists at the benzodiazepine receptor, like the conventional benzodiazepines
      and zopiclone or zolpideme, are indicated in short-lasting adjustment insomnia as
      well as in long-lasting psychophysiological insomnia. Regarding the duration of
      prescription the German Sleep Society recommends a period of 14 days in de novo
      patients, which can be repeated once only. In persisting insomnias further
      approaches should disregard benzodiazepine receptor agonists, but rely on other
      classes of substances such as tricyclic antidepressants instead. If such
      approaches are ineffective, the intake of benzodiazepine receptor agonists may be
      extended to 6 months, when a sleep log and objective observations have documented
      a true sleep deficit, when daytime impairment arises, when daytime impairment
      arises, when rebound insomnia, organic or mental insomnias and dependencies have
      been excluded, and when the indication is monitored at 14-day intervals. If the
      insomnia persists, during and in spite of therapy a specialist in sleep medicine
      should be consulted. If therapy is still ineffective after 3 months of daily
      treatment, a sleep laboratory should be consulted.

PMID- 7501088
TI  - [Clinical aspects and neurologic expert assessment in sequelae of whiplash injury
      to the cervical spine].
AB  - Whiplash injury to the cervical spine and its possible long-term sequelae, the
      late (or chronic) whiplash syndrome, are analysed based on a clearly defined
      accident mechanism and an initial battery of investigations to exclude lesions
      other than those affecting the soft tissue of the neck region (i.e. the
      consequences of strain and sprain). Predictors are discussed that may point to a
      delayed and complicated recovery, with development of a complex array of
      symptoms. The pattern of this symptomatology, as reviewed on the basis of
      different neuropsychological investigations, appears inhomogeneous. Comparison
      with other non-traumatic conditions, such as the chronic fatigue syndrome, the
      fibromyalgia syndrome and chronic daily headache, as well as with chronic
      disturbances of cervical origin, reveals striking similarities. In cases of
      litigation, these circumstances require careful assessment of the patient's
      previous history and an extensive differential diagnosis. Whiplash injury to the
      cervical spine rarely results in disability and, if so, is only minor.

PMID- 7501089
TI  - [Paraneoplastic neurologic syndromes. Classification and diagnosis].
AB  - Paraneoplastic neurologic syndromes may be the presenting symptoms of cancer or
      appear during the course of the disease. Current knowledge of paraneoplastic
      syndromes is discussed on the basis of Henson and Urich's classification. The
      recognition of antineuronal antibodies in some neurologic paraneoplastic
      syndromes has had an impact on diagnostic possibilities. Additionally, there are
      new considerations relating to pathogenesis and therapy. Although the value and
      diagnostic yield of antineuronal antibodies are the subject of major discussion,
      they are already of significant diagnostic value in the diagnosis of
      paraneoplastic neurologic syndromes.

PMID- 7501090
TI  - [Bacterial brain abscess].
AB  - The most common symptom of brain abscesses are headache, nausea, fever,
      disturbance of consciousness, focal signs and seizures. CT is the most useful
      investigation, showing ring-enhancing lesions with perifocal edema. Systemic
      inflammatory signs, cerebrospinal fluid changes and cerebral enhancement on
      leukocyte scintigraphy are of limited diagnostic value. In 10-20% of cases,
      diagnosis can only be established by biopsy. The most frequent organisms are
      aerobic streptococci, anaerobes, gram-negative bacilli and staphylococci.
      Metronidazole in combination with a third-generation cephalosporin and--in
      certain cases--an antistaphylococcal antibiotic should be given for at least 4
      weeks. Conservative treatment can give satisfactory results in abscesses less
      than 2-3 cm in diameter. Medium-sized and deep-seated abscesses are treated by CT
      guided stereotactic aspiration. In very large abscesses with the risk of
      herniation craniotomy and excision are necessary. Mortality is nowadays 5-15% and
      does not depend on treatment modalities. Prognosis is mainly determined by the
      patient's level of consciousness on admission.

PMID- 7501091
TI  - [Transcranial Doppler ultrasound monitoring of patients with viral infections of
      the central nervous system].
AB  - Serial (days 1, 3, 5, 8, 14, 21 after admission) transcranial Doppler ultrasound
      measurements of the mean blood velocity (Vmean) and the pulsatility index (PI) in
      the middle, anterior and posterior cerebral arteries (MCA, ACA, PCA) and the
      basilar artery were performed in 35 consecutive patients (male, 20, female, 15,
      mean age: 37 +/- 19 years) with acute meningitis or meningoencephalitis thought
      to have arisen from viral infections. The Glasgow Coma Scale (GCS) and the TCD
      findings on days 1-8 were compared with the Glasgow Outcome Scale on day 21 (GOS,
      short-term outcome). Compared with the reference values recorded in 69 healthy
      volunteers, Vmean was significantly elevated in the MCA, ACA and PCA on days 1-3,
      and on day 5 in the MCA (P< 0.01-0.05). The PI was significantly increased on
      days 1-8 in all intracranial arteries (P < 0.001-0.05). With respect to the
      outcome, patients with a poor outcome (GOS score 1-3) were found to have had
      significantly more markedly elevated PI in all vessels on days 3-8 (P < 0.05)
      than the patients with a good outcome (GOS score 4 and 5). The linear regression
      coefficient for the relationship between the PI on days 3-8 and the GOS ranged
      from r = 0.35 to 0.48 (P < 0.01) in all vessels. However, the coefficient (r)
      between the GCS score on days 3-8 and GOS was more marked (day 3: r = 0.7545, P<
      0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501093
TI  - [Does a neurologic clinic need an inhouse cerebrospinal fluid/neurochemical
      laboratory? Results of a survey of 289 neurological clinics].
AB  - In 1993 and 1994 an official inquiry was carried out by the Deutsche Gesellschaft
      fur Neurologie into the existence of neurochemical laboratories in departments of
      neurology throughout Germany. The following results were obtained. Neurochemical
      laboratories are more often seen in neurology departments involved in routine or
      emergency diagnosis than in departments engaged only in rehabilitation. Nearly
      all departments with an intensive care unit in a university hospital (91%) and
      nearly half of those outside the university (46%) have their own neurochemical
      laboratory. Departments with their own neurochemical laboratories are
      characterized by the use of specialized immunological diagnosis, especially of
      the cerebrospinal fluid (e.g., immunoglobulins, isoelectric focusing), in
      contrast to departments that are not working in the field of emergency medicine
      and are not equipped with their own neurochemical laboratories. The latter mostly
      carry out screening tests (e.g., antiepileptic drug monitoring, tumor markers).
      The existence of a neurochemical laboratory in a neurology department does not
      lead to an undifferentiated increase in the number of laboratory tests, but
      reflects the need for specialized diagnosis in CSF and neuroimmunology.

PMID- 7501092
TI  - [Catamenial seizures--an analysis].
AB  - Catamenial seizures are defined as epileptic seizures occurring during distinct
      phases of the menstrual cycle (i.e., periovulatory, premenstrually and during
      menstruation). The cyclic changes of the gonadotropic hormones are thought to be
      the main cause of the seizures. This hypothesis is supported by results of animal
      experiments, which have shown oestrogens to increase neuronal excitability
      whereas progesterone lowered it. We investigated 21 women with epilepsy who
      reported a catamenial increase in seizure frequency. Only 24% of these women
      actually exhibited a catamenial manifestation in more than 75% of seizures. The
      incidence of catamenial seizures is reported in the literature to be between 10%
      and 72%. Catamenial seizures are treated with anticonvulsant drugs. However, when
      anticonvulsants have failed to suppress seizures, progesterone or progesterone
      derivates have been administered with success. We treated 16 patients with a
      synthetic GnRH-analogue to suppress the hormonal release of gonadotropins. Four
      of the six patients with only catamenial seizure manifestations and no other
      seizures became seizure free. Ten patients had catamenial seizures as well as
      seizures not related to the menstrual cycle. A decrease in seizure frequency by
      more than 50% was achieved in 7 of these 10 patients.

PMID- 7501094
TI  - [Sympathetic skin response in Parkinson syndrome].
AB  - Several tests of cardiovascular and gastrointestinal function have been approved
      for the diagnosis of autonomic regulation dysfunction in Parkinson's disease. In
      the present study we compared the diagnostic value of the sympathetic skin
      response (SSR) with the established methods. Ninety percent of the 20 patients we
      examined (10 women, 10 men, 46 to 80 years) showed pathological results in the
      cardiovascular function test. Fifty-five percent had a prolonged colon transit,
      indicating a gastrointestinal dysfunction. We saw pathologically prolonged
      latencies of the SSR in 35% of the patients, 55% had borderline results. Three of
      the 20 patients had pathological results in all of the functions examined. Half
      of the patients had two pathological results, whereas 7 patients were
      pathological in only one of the three examinations. We were unable to establish
      any correlation between the SSR and other results, and we also found no
      relationship between prolonged SSR and the duration of the disease.

PMID- 7501095
TI  - [Encephalitis lethargica].
AB  - We report the case of a 34-year old patient who first complained of fever,
      confusion and transient ophthalmoplegia and then developed akinetic mutism,
      frontal lobe, pyramidal tract and extrapyramidal signs. Clinical and
      electrophysiological data support a diagnosis of encephalitis lethargica.
      Magnetic resonance imaging showed hyperintensive lesions in various brain
      regions. The patient responded to corticosteroid treatment. Two years after the
      onset of the first clinical signs he had recovered completely and today, after 5
      years, he shows no sign of disease.

PMID- 7501096
TI  - [Intracerebral hemorrhage and multiple brain abscesses caused by Bacillus cereus
      within the scope of acute lymphatic leukemia].
AB  - Multiple hematogenic brain abscesses in immunosuppression are occasionally caused
      by rare and primary apathogenic causative agents. We report a first case of an
      isolated CNS infection by Bacillus cereus, which led to death from multiple brain
      abscesses and an intracerebral hemorrhage, probably caused by the infection,
      within 4 days. The underlying disease leading to immunosuppression was acute
      lymphatic leukemia in complete remission. In spite of antibiotic therapy the
      chemotherapy-induced neutropenia enabled unhindered spreading of the necrotizing
      infection, which was verified by histological analysis. The production of potent
      toxins such as hemolysin and cerelolysin by B. cereus leads to rapid and
      fulminant tissue destruction usually involving the walls of blood vessels.

PMID- 7501098
TI  - [Local thrombolytic treatment of spontaneous intracerebral hemorrhage with
      plasminogen activator (rt-PA). Indications and limits].

PMID- 7501097
TI  - [Meningitis after travel in the Mediterranean region, caused by the sandfly fever
      virus].
AB  - Sandfly fever virus is the causative agent of sandfly fever (pappataci fever).
      The virus is endemic in the Mediterranean region and is transmitted by bites of
      Phlebotomus species. The three sandfly fever virus serotypes, Sicilian (SFS),
      Naples (SFN) and Toscana (TOS), are of travel-related significance. In addition
      to a flu-like illness, the sandfly fever virus may result in a serious
      neurological disease with meningitis and encephalitis. Due to the high number of
      travelers may occur in nonimmune persons. Since many clinicians are not aware of
      this disease, sandfly fever is still rarely diagnosed.

PMID- 7501099
TI  - Intentional cranial deformation: a disappearing form of self-mutilation.
AB  - Of the forms of human self-mutilation that have been recorded, few have been so
      widespread and long lasting as intentional cranial deformation. The earliest
      known record of the practice is from Iraq and dates back to 45,000 BC. The
      custom, which was practiced in many areas of the world, continued well into this
      century. Although tatooing, ear piercing, and circumcision are commonly practiced
      in our society, cranial deformation has almost completely disappeared from
      contemporary cultures, with the exception of isolated groups in Africa and South
      America. Intentional cranial deformation is intriguing for those who study the
      human cranium.

PMID- 7501100
TI  - Pineoblastoma in adults.
AB  - This is the first report of a series of adults (> 16 years of age) with
      pineoblastomas who had their entire neuraxis staged at the time of diagnosis.
      Between 1975 and 1992, seven men and four women with histologically proven
      pineoblastomas were evaluated at the University of California, San Francisco. The
      median age at diagnosis was 36 years (range, 17-59 yr). All patients presented
      with symptomatic hydrocephalus. One patient had a complete surgical resection,
      eight had subtotal resections, and two had biopsies only. One patient refused any
      treatment or follow-up review and died 6 months after diagnosis. The five
      patients with positively staged disease had progression either focally or in the
      spine 8 to 49 months (median, 10 mo) after initial diagnosis and died 1 to 20
      months after recurrence; the median overall survival time from the date of
      surgery was 30 months. In contrast, all five patients with negatively staged
      disease were alive without disease progression after a median of 26 months of
      follow-up. Our retrospective review shows that the extent of disease at diagnosis
      seems to be an important prognostic factor for pineoblastomas, as is true for
      medulloblastomas and other primitive neuroectodermal tumors. Initial staging
      should include examination of the cerebrospinal fluid and magnetic resonance
      imaging of the spine. Although patients with pineoblastomas are often treated
      with adjuvant systemic chemotherapy after craniospinal irradiation, the benefits
      of this approach are unclear.

PMID- 7501101
TI  - Frontal lobe changes after severe diffuse closed head injury in children: a
      volumetric study of magnetic resonance imaging.
AB  - In view of the pathophysiology and biomechanics of severe closed head injury
      (CHI) in children, we postulated that the frontal lobes sustain diffuse injury,
      even in the absence of focal brain lesions detected by magnetic resonance imaging
      (MRI). This study quantitated the morphological effects of CHI on the frontal
      lobes in children who sustained head trauma of varying severity. The MRI findings
      of 14 children who had sustained severe CHIs (Glasgow Coma Scale score of < or =
      8) were compared with the findings in a matched group of 14 children having
      sustained mild head injuries (Glasgow Coma Scale score of 13-15). The patients
      ranged in age from 5 to 15 years at the time of their MRIs, which were acquired
      at least 3 months postinjury. MRI findings revealed no focal areas of abnormal
      signal in the frontal lobes. Volumetric analysis disclosed that the total
      prefrontal cerebrospinal fluid increased and the gray matter volume decreased in
      the patients with severe CHI, relative to the mildly injured comparison group.
      Gray matter volume was also reduced in the orbitofrontal and dorsolateral regions
      of the brains of children with severe CHI, relative to the children who sustained
      mild head trauma. These volumetric findings indicate that prefrontal tissue loss
      occurs after severe CHI in children, even in the absence of focal brain lesions
      in this area. Nearly two-thirds of the children who sustained severe CHIs were
      moderately disabled after an average postinjury interval of 3 years or more,
      whereas 12 of the 14 patients with mild CHIs attained a good recovery (2 were
      moderately disabled) by the time of study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501103
TI  - On the pathogenesis of the radiculopathy complicating multilevel corpectomy.
AB  - Postoperative fifth cervical radiculopathy has been described after cervical
      corpectomy. One explanation for this complication is thought to be the factor of
      traction on cervical roots caused by a shifting of the spinal cord consequent to
      decompression. This theory is supported by our experience with 176 patients
      undergoing corpectomies for whom a lesser width of decompression all but
      eliminated the complication.

PMID- 7501102
TI  - Crush injuries to the head in children.
AB  - Although the majority of head injuries in children and adults involve dynamic
      loading conditions, some patients suffer static loading. Static loading occurs
      when forces are applied slowly to the head, and it produces a much different
      pattern of injuries. Crush injuries are usually described in the context of
      industrial accidents, but in our experience, these injuries are not rare in
      children. We report a series of seven crush injuries in young children admitted
      during a period of 29 months and describe our experience in the evaluation and
      treatment of this complex entity. Patient ages ranged from 15 months to 6 years.
      In four cases, the child's head was run over by a motor vehicle backing up in a
      driveway or parking lot. In the three other patients, the static loading occurred
      when the child climbed or pulled on a heavy object, which then fell over with the
      child and landed on the child's head. One child with cervicomedullary disruption
      died shortly after his arrival at the hospital. The others showed varying degrees
      of soft tissue injury to the face and scalp, with Glasgow Coma Scale scores
      ranging from 7 to 15. Computed tomograms and magnetic resonance images showed
      multiple and often extensive comminuted calvarial fractures, as well as
      subarachnoid and parenchymal hemorrhages. All patients had basilar cranial
      fractures. There was one cervical spine injury but no major vascular injuries.
      One child had pituitary transection, four had cranial nerve palsies, and another
      developed a delayed cerebrospinal fluid rhinorrhea 18 months after injury. All
      children made good cognitive recoveries, with some having relatively mild fixed
      focal deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501104
TI  - Complications of cervical discography: analysis of 4400 diagnostic disc
      injections.
AB  - Despite extensive experience with diagnostic cervical disc injection, the role of
      this procedure in the evaluation of patients with degenerative disc disease and
      severe neck pain remains controversial. Beyond the debate regarding its efficacy
      in identifying the site of cervical symptomatology and directing appropriate
      intervention are the potential morbidity and mortality associated with this
      diagnostic procedure. Discitis, subdural empyema, spinal cord injury, vascular
      injury, and prevertebral abscess have all been reported as complications of
      diagnostic cervical disc injection. Any meaningful assessment of the role of
      cervical discography in the evaluation of degenerative disc disease must include
      a determination of the risks inherent in the procedure. We retrospectively
      analyzed 4400 cervical disc injections in 1357 patients performed by an
      experienced radiologist between 1988 and 1993 to define the morbidity and
      mortality associated with discography. In addition, we reviewed the extant
      medical literature on the complications of this controversial procedure. This
      study demonstrates significant complications from diagnostic discography
      procedures occurring in less than 0.6% of the patients and 0.16% of the cervical
      disc injections.

PMID- 7501106
TI  - Intracerebroventricular administration of morphine for control of irreducible
      cancer pain.
AB  - Intracerebroventricular morphine analgesic for the treatment of cancer pain was
      administered, using implanted access ports, in 82 patients from 1984 to January
      1994. All of the patients who were selected for treatment were no longer
      responsive and had developed drug side effects to oral or parenteral opiates in
      varying doses (60-400 mg/d). The mean follow-up was 66 days (range, 12-443 d) for
      this series of 82 patients. The effective control of pain was achieved in nearly
      all of the patients, with only two failures. During the treatment, the daily
      morphine doses were moderately increased. The initial doses of morphine were a
      mean of 0.30 mg (range, 0.10-2 mg), and the final doses were a mean of 2.5 mg
      (range, 0.10-60 mg). The results show that the ratio of the terminal dose to the
      initial dose increased more rapidly for patients who had a follow-up of over 60
      days. However, the increase seems to have been because of the progress of the
      disease rather than because of drug tolerance.

PMID- 7501105
TI  - Antibiotic penetration into cervical discs.
AB  - Antibiotics are frequently prophylactically administered in surgical procedures
      to reduce the incidence of infection. The penetration of antibiotics into lumbar
      discs has been studied with mixed results, but penetration into cervical discs
      has not been reviewed. In this study, we examined the penetration of two commonly
      used antibiotics, oxacillin and cefazolin, into cervical discs. Eighteen patients
      with a total of 30 discs removed were studied. Two groups, each consisting of
      four patients with five discs removed, received either 1 g of oxacillin or 1 g of
      cefazolin by a single, preoperative intravenous infusion. Two other groups, each
      consisting of five patients with 10 discs removed, received either 2 g of
      oxacillin or 2 g of cefazolin, also by a single, preoperative intravenous
      infusion. A blood specimen, from which serum antibiotic levels were determined,
      was obtained from each patient simultaneously with each discectomy. The time
      interval between the antibiotic infusion and discectomy/phlebotomy was also
      recorded. Antibiotic levels were detected in all discs removed but were
      quantifiable in only 12. Nine of these 12 had been exposed to cefazolin. Of these
      nine discs, one was from a patient who had received 1 g whereas the other eight
      were from patients who had received 2 g of cefazolin. This represents 80% of the
      removed discs exposed to 2 g of cefazolin (10 discs total) and 20% exposed to 1 g
      (5 discs total). The remaining three discs with quantifiable antibiotic levels
      had been exposed to 2 g of oxacillin, which represents 30% of the discs (10
      total) exposed to that dose of oxacillin. Although cervical disc space infections
      are rare, they are serious.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501107
TI  - Spinous process-splitting laminoplasty with an extended foraminotomy for cervical
      myelopathy.
AB  - We present the surgical results of a laminoplasty with an extended foraminotomy
      for cervical myelopathy. We chose spinous process-splitting laminoplasty, because
      it gave us the opportunity to perform bilateral foraminotomies through the same
      exposure. An extended foraminotomy means that root decompression is performed as
      far laterally as possible, using the surgical microscope. We performed this
      method in 18 patients and experienced favorable clinical results.
      Neuroradiological evaluations revealed good decompression of the spinal cord
      postoperatively. Although the operation time needed was longer compared with the
      original method, the average blood loss was 430 ml and blood transfusion was
      necessary in five patients. This method can be considered when cervical
      myelopathy is treated by a posterior approach.

PMID- 7501108
TI  - Cost effectiveness analysis: a review.
AB  - Medical treatments and strategies are increasingly being subjected to evaluations
      of economic efficiency. Although the reasons for this are many, it is becoming
      ever more important for physicians to have an understanding of the uses and
      limitations of such evaluations. Cost effectiveness analysis (CEA) is a technique
      that measures the cost of medical technology per unit of a defined health output,
      usually life years saved with an adjustment for quality of survival. CEA is a
      popular method of economic evaluation for policy markers, because it can provide
      direct comparisons among many medical technologies, resulting in a ranked order
      of procedures based on economic efficiency. The proper interpretation of a CEA
      requires an understanding of the component parts of the analysis, their
      theoretical bases, and their limitations. The components of a CEA include the
      determination of relevant costs, an appropriate analysis viewpoint, the use of
      discounting for both costs and benefits, and a sensitivity analysis of the
      assumptions and probabilities that drive the analysis. Marginal and incremental
      CEAs are techniques that help to address the cost effectiveness of different
      amounts of a particular treatment and the differential costs and benefits of
      competing strategies, respectively. A review is presented of the theoretical
      basis of CEA and its component parts. Emphasis is placed on generating an
      understanding of the method rather than providing a step-by-step protocol for the
      undertaking of such studies.

PMID- 7501109
TI  - The cost effectiveness of stereotactic radiosurgery versus surgical resection in
      the treatment of solitary metastatic brain tumors.
AB  - Solitary metastatic brain tumors are the most common intracranial neoplasms
      encountered by neurosurgeons. Surgical resection of brain metastasis with whole
      brain radiotherapy (WBR) significantly increases survival in comparison with WBR
      alone. Stereotactic radiosurgery (SR) seems to provide results that are similar
      to those of surgical resection. To analyze the economic efficiency of these
      different treatments, we compared the results of surgical resection and SR as
      reported in the medical literature between 1974 and 1994. We included studies in
      which: 1) at least 75% of patients received WBR; 2) study dates were in the
      computed tomography era (after 1975); 3) operative morbidity, mortality, and
      median survival were reported; 4) study dates were not included in a more recent
      update or review; 5) tumor histologies were reported; and 6) the cobalt-60 gamma
      unit was used for SR. Three surgical resection studies and one SR study met all
      entry requirements. The WBR baseline was developed from two prospective,
      randomized trials and used for incremental cost effectiveness analysis. We
      developed a model of typical resource usage for uncomplicated procedures,
      reported complications, and subsequent craniotomies (for recurrent tumor or
      radiation necrosis) for both treatment options. Costs were estimated from the
      societal viewpoint using the 1992 Medicare Provider Analysis and Review database
      with average cost:charge ratios for surgery and WBR. A survey of capital and
      operating costs from five sites was used for radiosurgery. Our analysis revealed
      that radiosurgery had a lower uncomplicated procedure cost ($20,209 versus
      $27,587), a lower average complication cost per case ($2,534 versus $2,874), and
      a lower total cost per procedure ($22,743 versus $30,461), was more cost
      effective ($24,811 versus $32,149 per life year), and had a better incremental
      cost effectiveness ($40,648 versus $52,384 per life year) than surgical
      resection. A sensitivity analysis revealed that large changes in key assumptions
      would be required to change the analysis outcome. Equalization of the incremental
      cost effectiveness of the two treatments would require one of the following: 1) a
      38.7% reduction in SR annual case volume, 2) a 34.7% increase in SR procedure
      cost, 3) a 18.8% reduction in surgical resection procedure cost, 4) a 240.5%
      increase in SR morbidity cost, 5) a 12.7% reduction in SR median survival, 6) a
      16.8% increase in surgical resection median survival. Elimination of all surgical
      resection morbidity cost would still result in superior incremental cost
      effectiveness for SR.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7501110
TI  - Quantitative, morphological, and somatotopic nuclear changes after facial nerve
      regeneration in adult rats: a possible challenge to the "no new neurons" dogma.
AB  - The anatomic reorganization of the subnucleus that controls the stylohyoid muscle
      (the stylohyoid subnucleus) within the brain stem facial nucleus was studied
      after regeneration of the facial nerve in adult rats. Horseradish peroxidase was
      injected into the right stylohyoid muscle 3 to 21 months after transection and
      repair of the right facial nerve at the level of the stylomastoid foramen.
      Position, number, and soma diameter of retrogradely horseradish peroxidase
      labeled motoneurons were established, as well as the rostro-caudal extension of
      the stylohyoid subnucleus. In experimental rats, the stylohyoid subnucleus showed
      either an ipsilateral (50% of the rats) or a bilateral representation. In all of
      the experimental rats, the motoneurons composing the stylohyoid subnucleus had a
      more dispersed horizontal distribution pattern when compared with controls. More
      than 80% of the motoneurons were located outside the borders of the normal
      stylohyoid subnucleus, either ventrally or, especially in the rostral sections,
      dorsally closer to the floor of the fourth ventricle. The mean rostro-caudal
      length of the stylohyoid subnucleus was 2028.6 +/- 152.7 microns. The mean
      motoneuron number was 481.4 +/- 109.5 (2.20-fold greater than control values),
      and the motoneuron diameter distribution ranged from 7 to 43 microns. This study
      demonstrates that after regeneration of the facial nerve in adult rats, major
      changes occur in both the location and number of motoneurons that make up the
      stylohyoid subnucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501111
TI  - Differential display of messenger ribonucleic acid: a useful technique for
      analyzing differential gene expression in human brain tumors.
AB  - In this study, a differential display method for messenger ribonucleic acid was
      successfully used to identify genes differentially expressed between normal human
      brain and malignant glioma tissues. A total of 60 differentially expressed
      sequences were initially identified, of which 21 were cloned and sequenced.
      Twenty of the cloned sequences represented novel genes, and one sequence
      represented a kinesin heavy chain (KHC) gene isoform. The KHC isoform was
      selected for further characterization. Northern blots of total ribonucleic acid
      isolated from normal brain and a glioblastoma were probed with our KHC probe and
      confirmed the differential expression of this gene. Expression analysis of a
      variety of normal human tissues demonstrated that this KHC isoform is expressed
      only in brain tissues, with no detectable expression in placenta, spleen, kidney,
      lung, liver, or skeletal muscle. Our results confirm the rapid and sensitive
      nature of the differential display technique in identifying differential gene
      expression. This method offers a means to identify new genes of biological
      interest in human brain tumors such as oncogenes, tumor suppressor genes, and
      tumor-specific markers.

PMID- 7501112
TI  - The antitumor effect of MX2, a new morpholino anthracycline, against malignant
      glioma cell lines and its subcellular distribution.
AB  - The chemotherapeutic effect of MX2 (3'-deamino-3'-morpholino-13-deoxo-10
      hydroxycarminomycin), a new lipophilic morpholino anthracycline, against rat C6
      and human T98G glioma cells, was examined in vitro and in vivo. The subcellular
      distribution of MX2 was also studied. The drug concentrations of MX2 required for
      the 50% inhibition of cell growth (IC50) for C6 and T98G cells were 25.5 +/- 1.3
      ng/ml and 70.6 +/- 6.8 ng/ml, respectively, which were much lower than the IC50
      values for nimustine (ACNU). A C6 subline resistant to ACNU, C6/ACNU, was
      established by continuous exposure to graded concentrations of ACNU. The IC50 of
      MX2 for C6/ACNU was 28.3 +/- 2.2 ng/ml, indicating no cross-resistance to MX2. In
      the rats bearing the intracerebral C6 tumors, the life span was increased by
      about 40 to 100% after intravenous administration of MX2 at doses ranging from 1
      to 3 mg/kg of body weight. Confocal laser scanning microscopy demonstrated
      visually the good accumulation of MX2 in the implanted intracerebral C6 tumors,
      as well as its predominant distribution in the cytoplasm over the nucleus in both
      cell lines in vitro. Ultrastructural studies also demonstrated the cytotoxic
      effects of MX2 against glioma cells. Our results suggest that MX2 may be a useful
      chemotherapeutic agent in the treatment of malignant gliomas and that confocal
      laser scanning microscopy is useful for the study of the cellular
      pharmacokinetics of anthracycline derivatives, such as MX2.

PMID- 7501113
TI  - Immunohistochemical detection of progesterone receptors and the correlation with
      Ki-67 labeling indices in paraffin-embedded sections of meningiomas.
AB  - Female sex steroids may play a role in the proliferation of meningiomas. We
      investigated the progesterone receptor (PgR) immunoreactivities and the Ki-67
      labeling indices in the formalin-fixed, paraffin-embedded sections of meningiomas
      from 39 patients. After autoclave pretreatment of the sections (which were
      immersed in a citrate buffer), the sections were incubated with the monoclonal
      antibody for the PgR and the MIB-1 monoclonal antibody for the Ki-67 antigen. In
      the meningiomas studied, the immunoreactivity for the PgR was moderately to
      strongly positive in 51%, weakly positive in 21%, and negative in 28%. The
      nuclear staining for the PgR was clear, and no tumors were positive for the
      estrogen receptor. The Ki-67 labeling indices of the PgR-positive meningiomas
      (mean +/- standard deviation, 2.35 +/- 2.12%) were significantly lower than those
      of the PgR-negative meningiomas (6.53 +/- 4.83%) (P < 0.05). Two meningiomas that
      had recurred more than once showed high Ki-67 labeling indices and negative
      immunostaining for the PgR. These findings indicate that the PgR status may be
      closely related to the growth potentials of the meningiomas. Our results confirm
      that the immunodetection of the PgR and the Ki-67 antigen on the paraffin
      sections of meningiomas provides a practical tool for estimating the biological
      behavior of the meningiomas.

PMID- 7501114
TI  - Cytotoxicity of cis-parinaric acid in cultured malignant gliomas.
AB  - The cytotoxic effects of cis-parinaric acid, a plant-derived 18-carbon
      polyunsaturated fatty acid, were assessed in vitro on normal and neoplastic glia.
      After being incubated for 24 hours in the presence of 12 mumol/L cis-parinaric
      acid, 36B10 glioma cultures demonstrated nearly 90% toxicity (unpaired Student's
      t test, P < 0.001). Similar results were obtained after the exposure of C6 rat
      glioma cultures, A172 human glioma cultures, and U-937 human monocytic leukemia
      cultures to cis-parinaric acid. In contrast, fetal rat astrocytes incubated with
      12 mumol/L cis-parinaric acid demonstrated no significant toxicity (3% reduction,
      P = 0.12); fetal rat astrocytes showed only 20% toxicity after exposure to 40
      mumol/L cis-parinaric acid (P = 0.001). The cytotoxic effects of cis-parinaric
      acid were antagonized with the addition of equimolar concentrations of alpha
      tocopherol. Enzyme immunoassay of treated 36B10 glioma supernatant fluid for 8
      isoprostane (a known oxidative metabolite) demonstrated a 10-fold increase of 8
      isoprostane over 24 hours (123.0 +/- 10.3 versus 10.0 +/- 0.7 pg/ml for control,
      P < 0.001). These studies indicate that cis-parinaric acid may be significantly
      cytotoxic to malignant glioma cells in concentrations that spare normal
      astrocytes and that the mechanism of cytotoxicity is related to an oxidative
      process. The selective cytotoxic effect of cis-parinaric acid we describe
      represents the first step in the development of new chemotherapeutic agents for
      gliomas; these new agents act by preferentially enhancing lipid peroxidation in
      neoplastic cells.

PMID- 7501115
TI  - The protective effects of thiopental on brain stem ischemia.
AB  - Thiopental, a barbiturate anesthetic, which at high doses suppresses cortical
      electroencephalogram activity, was evaluated as a neuroprotective agent in a dog
      model of reversible, hindbrain ischemia. Fourteen dogs were exposed to 20 minutes
      of isolated brain stem ischemia after pretreatment with 35 mg per kg of
      thiopental or placebo. Brain stem auditory evoked potentials (BAEPs) and regional
      cerebral blood flow were measured before and during the ischemia and for 5 hours
      after reperfusion. During the ischemic period, both control and thiopental
      treated animals experienced dramatic declines in the BAEPs to less than 10% of
      baseline. On reperfusion for 30 minutes, the BAEPs increased in both groups to
      near 40% of baseline. In the thiopental-treated animals, the BAEPs continued to
      recover variably to a mean of 70% of baseline by 5 hours of reperfusion. In
      contrast, untreated animals showed a decline in BAEPs after 30 minutes of
      reperfusion. The improved recovery of BAEPs in the thiopental-treated animals
      suggests that thiopental may be of some value as a cerebroprotective agent,
      although the mechanism remains unclear. The variability in recovery in this group
      implies that other factors play a significant role in mediating functional
      recovery from ischemic brain stem damage.

PMID- 7501117
TI  - Neurosurgery at the Radcliffe Infirmary, Oxford: a history.
AB  - Neurosurgery started in Oxford in 1938. In this article, we commence the story of
      Oxford neurosurgery with Thomas Willis and trace the historical thread through
      William Osler, Charles Sherrington, John Fulton, and Harvey Cushing to Hugh
      Cairns. The department in Oxford is renowned for the training of neurosurgeons.
      The initial stimulus for this was the abundance of neurosurgical and neurological
      expertise in Oxford during World War II with Cairns, and this tradition continued
      with Joe Pennybacker and his successors. The large and ever increasing work load
      ensures trainees a wide exposure to challenging neurosurgical problems. An
      increasing emphasis placed on research has resulted in the creation of two posts;
      each consists of half-time clinical neurosurgery and half-time research. Hugh
      Cairns organized the department along "Cushing lines." This organization still
      exists, allowing us to treat a large number of patients with relatively few beds
      and an average length of patient stay less than 6 days. We look to the future
      with confidence.

PMID- 7501116
TI  - Steroid hormone receptors in astrocytic neoplasms.
AB  - The presence of specific steroid hormone-binding receptors has been correlated
      with the clinical response to hormonal therapy in a number of different
      neoplasias, including breast and prostate cancer. In this article, we
      investigated the expression of the androgen, estrogen, glucocorticoid, and
      progesterone receptor messenger ribonucleic acid (mRNA) and protein in a number
      of astrocytic neoplasms of various histological grades. Androgen and
      glucocorticoid receptor mRNA were detected in all astrocytic neoplasms examined,
      regardless of histological subtype. In contrast, progesterone receptor mRNA was
      observed more frequently in high-grade tumors than in low-grade tumors. Estrogen
      receptor mRNA was undetectable in all astrocytic tumors examined. These studies
      suggest a possible adjunct clinical use of hormonal therapy for the treatment of
      astrocytomas. Specific antagonists and agonists may allow the modulation of the
      growth of these tumors. Development of this body of knowledge may lead to the
      development of better treatment for these aggressive tumors.

PMID- 7501118
TI  - Hydrocephalus first illustrated.

PMID- 7501119
TI  - Two-year follow-up study of a patient with Parkinson's disease and severe motor
      fluctuations treated by co-grafts of adrenal medulla and peripheral nerve into
      bilateral caudate nuclei: case report.
AB  - We performed co-grafts of adrenal medulla and peripheral nerve into the bilateral
      caudate nuclei of a 43-year-old patient with advanced Parkinson's disease who
      showed severe daily motor fluctuations before surgery. There were no
      postoperative complications, and a 2-year follow-up result is presented. The
      patient showed a gradual and significant amelioration of the parkinsonian
      symptoms starting 2 weeks after transplantation. The alleviation of akinesia
      during "off" periods was the most apparent clinical improvement and continued for
      2 years after surgery. The dosage of L-dopa/benserazide was significantly reduced
      after surgery compared with that before surgery. The results indicate that co
      grafts of adrenal medulla with peripheral nerve may be useful for the treatment
      of Parkinson's disease in the long term.

PMID- 7501120
TI  - Tremor as the result of shunt obstruction: four patients with cysticercosis and
      secondary parkinsonism: report of four cases.
AB  - In four patients, shunt obstruction was accompanied by severe resting tremor
      involving principally the head, the jaw, the tongue, and the right upper
      extremity. Shunt revision resulted in improvement in each patient. Five similar
      patients have been reported. Although rare, the occurrence of parkinsonian tremor
      in a previously shunted patient suggests obstruction and requires prompt
      evaluation.

PMID- 7501121
TI  - Traumatic brain injury associated with an intradiploic epidermoid cyst: case
      report.
AB  - We present a case of an intradiploic epidermoid cyst with an unusual
      complication. After a minor fall, a patient with a large right parietal
      epidermoid suffered a traumatic brain injury caused by the transfer of the force
      of the fall through the cyst contents to the brain and by transdural herniation
      of the cyst contents into brain parenchyma. Elective resection of intradiploic
      epidermoids associated with large bony defects is recommended to avoid this
      apparently rare but potentially dangerous complication of an otherwise benign
      condition.

PMID- 7501122
TI  - Growth, hemorrhage, and regression of multiple intracerebral vasoformative
      tumors: report of an unusual case.
AB  - A rare case of multiple hemorrhagic vascular tumors of the cerebrum and
      cerebellum is reported. Computed tomographic scans in a 16-year-old girl revealed
      multifocal brain lesions with "jewel ring"-like areas of contrast enhancement. An
      old hematoma cavity was found inside the surgical specimen. Histologically, it
      was a vascular tumor composed of anastomosing vascular channels with
      proliferating endothelial cells and hemorrhages at different stages. Upon further
      histopathological study, this lesion could not be classified as any known
      vascular tumor entity, although it resembled some vascular tumors, such as
      cavernous hemangioma and hemangioendothelioma. The patient received steroid and
      alpha interferon treatment. The lesions initially increased in number once, then
      resolved 10 months after onset. The neuroradiological and histopathological
      features in the present case were characteristic, and the clinical course was
      unusual.

PMID- 7501123
TI  - Resolution of traumatic hypertrophic periodontoid cicatrix after posterior
      cervical fusion: case report.
AB  - The case of a 38-year-old man with delayed myelopathy 19 years after a nontreated
      odontoid type II fracture is reported. Magnetic resonance imaging of the
      craniocervical region revealed a periodontoid cicatrix. The clinical syndrome
      improved, and complete resolution of the retro-odontoid mass was achieved 9
      months after posterior cervical fixation. The implications of this unique case
      for the management of myelopathy associated with nonunion of odontoid fractures
      are discussed.

PMID- 7501125
TI  - Posterior interosseous nerve palsy after brachiocephalic arteriovenous fistula
      construction: report of two cases.
AB  - Two cases of delayed posterior interosseous nerve palsy after brachiocephalic
      arteriovenous fistula creation are presented. Both patients suffered from end
      stage renal disease, necessitating chronic hemodialysis. After fistula
      construction, both developed progressive weakness of the muscles innervated by
      the posterior interosseous nerve. One patient also demonstrated sensory loss in
      the distribution of the superficial radial nerve. Electrophysiological studies
      confirmed posterior interosseous mononeuropathies in both cases. Surgical
      exploration demonstrated posterior interosseous nerve continuity, with severe
      compression from the hypertrophied venous limb of the arteriovenous fistula. The
      superficial radial nerve was also compressed in one patient. After neurolysis and
      fistula revision, both patients recovered neurological function.

PMID- 7501124
TI  - Pediatric spinal blastomycosis: case report.
AB  - A 5-year-old male patient presented with flank pain, limping, weight loss, and
      cachexia. Magnetic resonance imaging revealed destructive vertebral changes, an
      epidural mass, psoas abscesses, and lack of involvement of the disc spaces.
      Blastomyces dermatitidis was isolated from a needle aspiration specimen. Sparing
      of the disc spaces, an unusual finding, suggested that the spread of infection
      was by way of paravertebral structures and surrounding potential spaces.
      Management was simplified by using gadolinium contrast-enhanced magnetic
      resonance imaging, which indicated that the epidural mass was mainly solid,
      thereby obviating abscess drainage.

PMID- 7501126
TI  - Resection of giant invasive pituitary tumors through a transfacial approach:
      technical case report.
AB  - Giant invasive pituitary adenomas are rare tumors that have been reported to
      extensively involve the cranial base, as well as other intra- and extra-cranial
      structures, making surgical resection by traditional approaches impossible. We
      report two cases, each of a giant invasive adenoma involving the entire length of
      the clivus and adjacent structures that was resected via a transfacial approach
      with excellent results. Both tumors were in middle-aged men; one was
      nonsecreting, and the other secreted follicle-stimulating hormone alpha-subunit.
      Most previously reported giant invasive adenomas have been prolactinomas. Both
      tumors were resected via a transfacial approach that incorporated an osteoplastic
      maxillotomy with palatal division and a posterior pharyngeal incision that
      provided exposure from the suprasellar region to C2. Both of the patients
      received postoperative radiation and have done very well. Their cosmetic results
      were excellent. The complications included postoperative meningitis in one
      patient and a nasal voice in the other. The transfacial approach provides
      excellent access for this type of extensive midline tumor requiring resection
      from the suprasellar region down to the foramen magnum.

PMID- 7501127
TI  - Treatment of hypertensive cerebellar hemorrhage--surgical or conservative
      management?

PMID- 7501128
TI  - Cases of intracranial pressure.

PMID- 7501129
TI  - An introduction to the biology of consciousness.
AB  - This paper summarizes the main steps in a scientific study of consciousness. From
      a survey of the recent literature, it appears that: (1) there is a clear tendency
      to consider consciousness as a scientific object; (2) consistent subjective and
      objective descriptions of consciousness are possible; an intentional-modeling
      structure accounts for its main features; (3) from the evolutionary biology
      standpoint, conscious cognitive activities, as based on models of the self, the
      world and the alter-ego, have a functional value; (4) the material basis of
      consciousness can be clarified without recourse to new properties of the matter
      or to quantum physics. Current neurobiology, based on classical macrophysics,
      appears able to handle the problem. In this scope, the neurobiology of sleep
      wakefulness and attention, and neuropsychology, have already achieved substantial
      advances.

PMID- 7501130
TI  - Consciousness: perspectives from symbolic and connectionist AI.
AB  - While consciousness has not been a major concern of most AI researchers, some
      theorists have tried to explore how computational models might explain
      consciousness. I explore how far computational models might go in explaining
      consciousness, focusing on three aspects of conscious mental states: their
      intrinsic intentionality, the awareness a subject has of the contents of these
      intentional states, and the distinctive qualitative character of these states. I
      describe and evaluate strategies for developing connectionist systems that
      satisfy these aspects of consciousness.

PMID- 7501131
TI  - The neurobiology of human consciousness: an evolutionary approach.
AB  - Human brains are basically primate in design, but in addition have
      representational mechanisms that give human consciousness a special character.
      The evolution in hominids of new kinds of representational skill--both nonverbal
      and verbal--produced our capacity for skilled rehearsal and explicit memory
      retrieval, and allowed the invention of conventional, or public representations,
      including languages and external symbols. The latter have created demands at the
      cultural level that greatly influence the deployment of cerebral resources. The
      spiralling interaction of brain and culture in evolution has resulted in a unique
      quasi-modular architecture at the highest levels of human cerebral integration.

PMID- 7501132
TI  - Consciousness and the natural method.
AB  - 'Consciousness' is a superordinate term for a heterogeneous array of mental state
      types. The types share the property of 'being experienced' or 'being experiences'
      -'of there being something that it is like for the subject to be in one of these
      states.' I propose that we can only build a theory of consciousness by deploying
      'the natural method' of coordinating all relevant informational resources at
      once, especially phenomenology, cognitive science, neuroscience and evolutionary
      biology. I'll provide two examples of the natural method in action in mental
      domains where an adaptationist evolutionary account seems plausible: (i) visual
      awareness and (ii) conscious event memory. Then I will discuss a case, (iii),
      dreaming, where I think no adaptationist evolutionary account exists. Beyond
      whatever interest the particular cases have, the examination will show why I
      think that a theory of mind, and the role conscious mentation plays in it, will
      need to be built domain-by-domain with no a priori expectation that there will be
      a unified account of the causal role or evolutionary history of different domains
      and competences.

PMID- 7501133
TI  - Cerebral correlates of visual awareness.
AB  - While it may be a long time before we can specify the mechanisms through which a
      brain process achieves awareness, it may be possible to determine as a first step
      whether awareness is limited to the products of certain kinds of processing. In
      the domain of vision, for example, perceptual awareness might only be attainable
      in association with object-centred coding, configural representations of space,
      and other such forms of abstracted (non-retinocentric) coding. It appears that
      these forms of visual coding are anatomically restricted to telencephalic
      structures, and indeed it has been argued that they may be peculiar to, or at
      least visually dependent upon, the 'ventral stream' of visual areas with the
      cortex. It is suggested here that such a brain process would still not be able to
      enter visual awareness unless it was selectively amplified through neuronal
      gating of the kind that has been shown to be correlated with selective spatial
      attention. The present paper explores the extent to which this putative dual
      requirement for visual consciousness might form a basis for understanding the
      various phenomena of "covert vision" seen in patients suffering from hemianopia,
      apperceptive agnosia, and unilateral spatial neglect.

PMID- 7501134
TI  - Memory and consciousness: a selective review of issues and data.
AB  - Methods for dissociating and independently studying conscious (explicit) and
      unconscious (implicit) memory are discussed. Recent work in the field of amnesia
      is then briefly reviewed, focusing on the question of how clearly the disorder
      fractionates according to the implicit-explicit distinction. Finally, evidence
      supporting dual-process models of recognition memory is reviewed, and data
      suggesting that amnesic patients have relatively spared familiarity-based
      recognition memory are critically assessed.

PMID- 7501135
TI  - Dopamine release in the nucleus accumbens: the perspective from aberrations of
      consciousness in schizophrenia.
AB  - Studies of the cognitive abnormalities that underlie positive symptoms in acute
      schizophrenia, and animal experiments that attempt to model similar cognitive
      abnormalities and to elucidate the brain mechanisms underlying them, suggest that
      the release of dopamine from A 10 terminals in the nucleus (n.) accumbens, in
      interaction with the projection to n. accumbens from the retrohippocampal region,
      is closely related to stimulus salience and perhaps to the heightened states of
      awareness reported by schizophrenics.

PMID- 7501136
TI  - Conscious and pre-conscious processes as seen from the standpoint of sleep-waking
      cycle neurophysiology.
AB  - The literature on state-dependent fluctuations in thalamocortical activities
      indicates that in electrophysiological terms, waking and paradoxical sleep are
      fundamentally identical states, with the provision that the handling of sensory
      information is altered in REM sleep. The central paradox of REM sleep, namely the
      apparent lack of cognitive responsiveness to sensory stimulation in spite of
      increased thalamocortical responsiveness to sensory stimuli, will lead us to
      hypothesize that the processing of sensory inputs in REM sleep is similar to that
      underlying preconscious processing of sensory inputs in the waking state. This
      will lead to a general discussion of the role of fast (approximately equal to 40
      Hz) thalamocortical oscillations and temporal binding in sensory processing and
      conscious experience.

PMID- 7501137
TI  - An information processing theory of anaesthesia.
AB  - A theory of anaesthesia is presented. It consists of four hypotheses: (1) The
      occurrence of states of consciousness causally depends on the formation of
      transient higher-order, self-referential mental representations. The occurrence
      of such states is identical with the appearance of conscious phenomena. Loss of
      consciousness will occur, if and only if the brain's representational activity
      falls below a critical threshold. (2) Mental representations are instantiated by
      neural cell assemblies. (3) The formation of assemblies involves the activation
      of the NMDA receptor channel complex. The activation state of this receptor
      determines the rate at which assemblies are generated. (4) General anaesthetics
      have a common operative mechanism: they directly or indirectly affect the
      function of the NMDA system.

PMID- 7501138
TI  - Cerebral bases of consciousness: a historical view.
AB  - Attempts of modern brain research, starting at the end of the nineteenth century,
      to define and hierarchically order consciousness are reviewed. It is emphasized
      that roots from philosophy, biology, and psychology influenced brain research in
      its search for possible physical bases of consciousness. Among the mainstreams of
      research were approaches which defined consciousness by selecting numerous
      attributes of it and ordering these hierarchically. Similarly, there was
      widespread speculation on whether all kinds of animals or only some of them are
      conscious or manifest some of the hierarchically defined attributes of
      consciousness. On the brain side, the cerebral cortex and in particular its
      frontal aspects, the prefrontal cortex, was regarded as the principal anatomical
      basis of consciousness. The dependence of consciousness on memory and the ability
      to order processes in time were widely acknowledged and case descriptions from
      Korsakoff patients and epileptics were considered especially to demonstrate the
      interdependence between consciousness and the brain.

PMID- 7501139
TI  - Yom Kippur headache.
AB  - Fasting is frequently mentioned by patients and in textbooks as a trigger for
      headache. In this study, we attempted to define the role of fasting as a possible
      precipitator of headache. Headache history was documented in 370 hospital
      employees (60% female) before and immediately after a 25-hour fast for the 1993
      Day of Atonement (Yom Kippur). The population included 211 who fasted; 39% of
      fasters developed headache, compared with only 7% of nonfasters (p < 0.000001).
      Headache was usually of a nonpulsating quality, mild to moderate in intensity,
      and bilateral and frontal in location. Subjects with a history of headache were
      more likely to develop fasting-induced headache than were those without such
      history (66% versus 29%, p < 0.000002). The number of headache sufferers
      increased in direct relation to the duration of the fast. Caffeine and nicotine
      withdrawal and oversleeping did not appear to have an influence on headache
      development. We conclude that fasting is a strong headache precipitator,
      especially among chronic headache sufferers. It is usually nonpulsating and
      nonlateralized.

PMID- 7501141
TI  - Neurotoxicity in liver transplant recipients with cyclosporine immunosuppression.
AB  - We studied the clinical features, blood levels of cyclosporine, and neuroimaging
      findings in 46 patients with cyclosporine neurotoxicity after liver
      transplantation. The clinical presentation of cyclosporine neurotoxicity was
      characterized by tremulousness and restlessness in all patients and was
      associated with acute confusional state and psychosis in 20 patients, seizures in
      eight, speech apraxia or action myoclonus speech in three, and cortical blindness
      in two. In 35 patients, cyclosporine neurotoxicity occurred during IV treatment.
      Neuroimaging studies showed only minor white matter abnormalities in two patients
      despite dramatic clinical presentations, including speech difficulties, seizures,
      and cortical blindness. In only 19 of 31 patients (61%) did trough levels of
      cyclosporine suggest neurotoxicity. Neurologic findings were reversible in all
      patients after cyclosporine was withheld and then given in lower dosage. In three
      patients, substituting FK 506 did not result in neurotoxicity.

PMID- 7501140
TI  - Fatigue therapy in multiple sclerosis: results of a double-blind, randomized,
      parallel trial of amantadine, pemoline, and placebo.
AB  - OBJECTIVE: To determine the relative efficacy of amantadine, pemoline, and
      placebo in treatment of multiple sclerosis (MS)-related fatigue. BACKGROUND:
      Fatigue is a complication of MS. Both pemoline and amantadine have been used to
      treat MS fatigue, but their relative efficacy is not known. METHODS: Amantadine,
      pemoline, and placebo were compared in a randomized, double-blind, placebo
      controlled study using a parallel-group design. Ninety-three ambulatory MS
      patients completed the study. Primary outcome measures were the fatigue severity
      scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response
      determined by verbal self-report. Secondary outcome measures consisted of
      assessments of sleep, depression, and vitality. Repeated-measures analysis of
      variance with planned post-hoc contrasts and Fisher's exact test were used to
      compare treatment response. RESULTS: Amantadine-treated patients showed a
      significantly greater reduction in fatigue, as measured by the MS-FS, than did
      patients treated with placebo (p = 0.04). By verbal report at the end of the
      study, 79% of patients treated with amantadine versus 52% treated with placebo
      and 32% treated with pemoline preferred drug therapy compared with no treatment
      (p = 0.03). No significant differences in any primary outcome measures were noted
      between pemoline and placebo. Neither amantadine nor pemoline affected sleep or
      depression relative to placebo. CONCLUSION: Amantadine was significantly better
      than placebo in treating fatigue in MS patients, whereas pemoline was not. The
      benefit of amantadine was not due to changes in sleep, depression, or neurologic
      disability.

PMID- 7501143
TI  - Interleukin-2 binding proteins in sera from normal subjects and multiple
      sclerosis patients.
AB  - We previously reported elevations of interleukin 2 (IL-2) in the serum of
      patients with chronic progressive MS. Using gel chromatography, protein A
      sepharose affinity chromatography, and ELISAs for IL-2 and the IL-2 soluble
      receptor, we now demonstrate that this cytokine is bound to serum proteins. These
      serum proteins include antibodies to IL-2, soluble IL-2 receptors, and high
      molecular-weight proteins. Using a CTLL cell assay, a serum fraction
      corresponding to IgG antibodies to IL-2 inhibited the activity of this cytokine.
      Thus, we present evidence for potential immunomodulation of a pivotal cytokine in
      MS by serum proteins.

PMID- 7501142
TI  - Comparison and meta-analysis of randomized trials of endarterectomy for
      symptomatic carotid artery stenosis.
AB  - OBJECTIVE: Comparison and meta-analysis of randomized trials of carotid
      endarterectomy for symptomatic stenosis of the extracranial carotid artery.
      BACKGROUND: Randomized trials (North American Symptomatic Carotid Endarterectomy
      Trial [NASCET], the European Carotid Surgery Trial [ECST], and the VA Cooperative
      Study [VACS]) each show that carotid endarterectomy improves outcomes in selected
      symptomatic patients with high-grade extracranial carotid artery stenosis. Direct
      comparisons among the studies have not been possible because of differing
      methodologies, endpoints, and formats of data reporting. DESIGN/METHODS: Data for
      specified endpoints and corresponding person-years at risk were obtained for each
      trial. The rates of nonfatal stroke, nonfatal myocardial infarction, or death for
      surgically or medically treated patients in the perioperative period (30 days)
      and thereafter were compared (both including and excluding perioperative events)
      and then combined using meta-analytic techniques. Data from NASCET and ECST were
      also analyzed for differences in outcomes by sex. RESULTS: Event rate estimates
      (with 95% confidence intervals [95% CI]) for the first 30 days (events per person
      year, primarily nonfatal stroke) for medically treated patients were 0.44 (0.22
      to 0.76) for NASCET, 0.15 (0.04 to 0.38) for ECST, and 0.27 (0.03 to 0.96) for
      VACS. For surgically treated patients, the corresponding rates (per person-year)
      were 0.78 (0.49 to 1.19), 0.63 (0.41 to 0.94), and 1.27 (0.58 to 2.43). Event
      rates per year after 30 days were higher for medically treated patients (0.20
      [0.16 to 0.25] versus 0.08 [0.05 to 0.11] for NASCET; 0.12 [0.10 to 0.15] versus
      0.07 [0.06 to 0.09] for ECST; and 0.15 [0.07 to 0.25] versus 0.07 [0.03 to 0.16]
      for VACS). There were no significant differences among the trials, with an
      overall benefit for surgical therapy (risk ratio estimate, RR = 0.67, 95% CI =
      0.54 to 0.83). There were no significant sex-based differences between NASCET and
      ECST and the overall benefit was not significantly different for men and women
      (RR = 0.58, 95% CI = 0.45 to 0.74 for men; RR = 0.84, 95% CI = 0.57 to 1.25 for
      women). CONCLUSIONS: Adjusting for primary endpoints and duration of follow-up,
      carotid endarterectomy has a similar benefit for symptomatic patients across
      trials and a similar benefit for men and women.

PMID- 7501144
TI  - Accuracy of initial stroke subtype diagnosis in the TOAST study. Trial of ORG
      10172 in Acute Stroke Treatment.
AB  - Rapid identification of stroke subtype is valuable for both practicing clinicians
      and the optimal design of clinical stroke trials. Mechanisms of ischemic injury
      might differ among different stroke subtypes. Certain subtypes might be
      clinically identified as suboptimal for future therapeutic or prophylactic stroke
      trials. Some subtypes might be so clinically distinct that extensive laboratory
      investigation is unwarranted. Investigators in the ongoing Trial of ORG 10172 in
      Acute Stroke Treatment are using criteria to categorize stroke etiology among
      enrolled patients into one of five subtypes: large-artery atherothromboembolic,
      cardioembolic, small-vessel thrombotic, other etiology, or undetermined etiology.
      As part of the study, physicians initially predict the most likely subtype of
      stroke based on clinical features and baseline CT. Three months after stroke,
      investigators use the criteria, which also incorporate results of diagnostic
      testing, to reclassify stroke subtype. Initial clinical impression of subtype
      agreed with final determination in 62% of patients, and the rate was similar for
      all stroke subtypes. No stroke subtype was more accurately diagnosed than others
      by initial assessment. No subtype was more commonly identified by diagnostic
      studies. Fifteen percent of patients remained without a clear etiologic subtype
      diagnosis at 3 months. We conclude that clinical trials in stroke should not
      attempt to restrict entry into trials based on presumed stroke subtype. A careful
      evaluation for etiology is justified in all patients presenting with stroke,
      regardless of presumed subtype.

PMID- 7501145
TI  - Cognitive performance on the Alzheimer's Disease Assessment Scale: effect of
      education.
AB  - The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is
      used to monitor disease progression and treatment efficacy in clinical trials of
      Alzheimer's disease (AD). Using data from a 12-week drug trial, we
      retrospectively studied the effect of education on ADAS-Cog performance in a
      group of 444 patients with AD. The effect of education was statistically
      significant on baseline ADAS-Cog total scores. This effect remained statistically
      significant after controlling for age, gender, and dementia severity. Education
      effects were also statistically significant at week 12 for ADAS-Cog total and 10
      of 11 subitem scores in 138 AD patients in the placebo arm of the trial. Post hoc
      analysis showed that non-high school graduates performed worse than those with
      greater educational levels across a broad range of cognitive domains. Our
      results, in conjunction with reports linking lower educational level with a
      higher risk for AD, suggest that educational level of patients be given
      consideration in the design and interpretation of cognitive tests in AD drug
      trials.

PMID- 7501146
TI  - Alzheimer's disease with and without coexisting Parkinson's disease changes:
      apolipoprotein E genotype and neuropathologic correlates.
AB  - The frequency of the apolipoprotein E (ApoE) epsilon 4 allele and its
      relationship with coexistent Parkinson's disease (PD) neuropathology in
      Alzheimer's disease (AD) have not been extensively explored. We determined ApoE
      genotype in 100 dementia patients with neuropathologically confirmed AD with and
      without concomitant Parkinson's disease (PD) changes (nigral degeneration and
      Lewy bodies at various sites). Fifty "AD+PD" patients were matched closely with
      50 "pure AD" patients for age, sex, and duration of dementia. We found identical
      overrepresentation of the epsilon 4 allele in the two groups: 72% of the patients
      in each group had at least one ApoE epsilon 4 allele, compared with approximately
      25% in the general population (p < 0.005) and in our institutional autopsy
      population (p < 0.001). Age at onset varied inversely with epsilon 4 allele
      dosage in men but not in women in both the AD and the AD+PD groups. As with
      amyloid deposition and plaque frequency in AD, we observed an association between
      epsilon 4 dosage and PD-related changes. Specifically, the severity of ubiquitin
      positive neuritic change in CA2/3 of the hippocampus, but not the frequency of
      cortical Lewy bodies, varied significantly with epsilon 4 dosage in the AD+PD
      cases.

PMID- 7501147
TI  - The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part IX.
      A prospective cliniconeuropathologic study of Parkinson's features in Alzheimer's
      disease.
AB  - Although extrapyramidal signs such as rigidity, bradykinesia, and postural
      impairment frequently occur in patients with Alzheimer's disease (AD), the
      correlation of these parkinsonian manifestations with the neuropathologic changes
      of Parkinson's disease (PD) has not been well established. Previous
      clinicopathologic studies addressing this issue have been largely retrospective
      or have consisted of relatively small numbers of cases. We examined the
      neuropathologic correlates of clinical parkinsonism in 78 cases with autopsy
      confirmed AD prospectively enrolled in the Consortium to Establish a Registry for
      Alzheimer's Disease. Sixteen (20.5%) of the 78 AD cases showed concomitant PD
      pathology (AD/PD) as evidenced by the presence of nigral degeneration and Lewy
      bodies at any site. There were neocortical Lewy bodies in eight of these 16
      cases. Two or more clinical manifestations of extrapyramidal dysfunction were
      present in eight (50.0%) of the 16 cases of AD/PD versus 11 (17.7%) of the 62
      cases of AD alone (p < 0.01). Although semiquantitative ratings of the frequency
      of neuritic plaques showed no differences between the two groups, neurofibrillary
      tangles in the AD/PD group were less frequent in the midfrontal (p < 0.001) and
      superior temporal cortex (p < 0.05). These findings support previous reports that
      AD/PD cases are more likely to manifest extrapyramidal dysfunction and show
      plaque predominance at autopsy.

PMID- 7501148
TI  - Early differential diagnosis of Parkinson's disease with 18F-fluorodeoxyglucose
      and positron emission tomography.
AB  - Early-stage Parkinson's disease (EPD) is often clinically asymmetric. We used 18F
      fluorodeoxyglucose (FDG) and PET to assess whether EPD can be detected by a
      characteristic pattern of regional metabolic asymmetry. To identify this pattern,
      we studied 10 EPD (Hoehn and Yahr stage I) patients (mean age 61.1 +/- 11.1
      years) using 18F-FDG and PET to calculate regional metabolic rates for glucose.
      The scaled subprofile model (SSM) was applied to metabolic asymmetry measurements
      for the combined group of EPD patients and normal subjects to identify a specific
      covariation pattern that discriminated EPD patients from normal subjects. To
      determine whether this pattern could be used diagnostically, we studied a
      subsequent group of five presumptive EPD patients (mean age 50.9 +/- 18.3), five
      normal subjects (mean age 44.6 +/- 15.3), and nine patients with atypical drug
      resistant early-stage parkinsonism (APD) (mean age 44.6 +/- 14.0). In each member
      of this prospective cohort, we calculated the expression of the EPD-related
      covariation pattern (subject scores) on a case-by-case basis. We also studied 11
      of the EPD patients, five patients with APD, and 10 normal subjects with 18F
      fluorodopa (FDOPA) and PET to measure presynaptic nigrostriatal dopaminergic
      function, and we assessed the accuracy of differential diagnosis with both PET
      methods using discrimination analysis. SSM analysis disclosed a significant
      topographic contrast profile characterized by covariate basal ganglia and
      thalamic asymmetries. Subject scores for this profile accurately discriminated
      EPD patients from normal subjects and APD patients (p < 0.0001). Group
      assignments into the normal or parkinsonian categories with FDG/PET were
      comparable to those achieved with FDOPA/PET, although APD and EPD patients were
      not differentiable by the latter method. Metabolic brain imaging with FDG/PET may
      be useful in the differential diagnosis of EPD.

PMID- 7501149
TI  - Primary lateral sclerosis: a neuropsychological study.
AB  - Nine patients with clinically diagnosed, radiologically supported primary lateral
      sclerosis underwent cognitive testing. None was demented, but eight had mild
      cognitive impairment. Performances were most consistently impaired on
      neuropsychological tests sensitive to frontal lobe functions, followed by tests
      sensitive to memory. Cognitive testing may be useful in helping to establish a
      cortical localization in patients with the syndrome of progressive spasticity.
      There are potential nosologic relations between primary lateral sclerosis and
      other degenerative frontal lobe syndromes, such as frontal lobe dementia and
      progressive spasticity with dementia.

PMID- 7501151
TI  - Chronic myelopathy associated with human herpesvirus-6.
AB  - Human herpesvirus-6 (HHV-6) is implicated in a variety of neurologic diseases. We
      report a previously healthy elderly woman with progressive spastic paraparesis.
      At autopsy the spinal cord showed widespread demyelination, axonal loss, and
      chronic inflammation. HHV-6 DNA was amplified, using polymerase chain reaction,
      from spinal cord tissue, and glial cells were immunoreactive with an HHV-6
      antibody. These findings suggest that HHV-6 may cause myelopathy.

PMID- 7501150
TI  - Detection of Borrelia burgdorferi-specific antigen in antibody-negative
      cerebrospinal fluid in neurologic Lyme disease.
AB  - OBJECTIVE: To determine the potential of detection in CSF of specific Borrelia
      burgdorferi antigen, OspA, as a marker of infection in neurologic Lyme disease
      and compare this with the detection of antibody. DESIGN: CSF from 83 neurologic
      patients in an area highly endemic for Lyme disease was examined prospectively
      for (1) OspA by antigen capture ELISA and Western blot employing monoclonal
      antibodies, and for (2) B burgdorferi antibodies by ELISA. RESULTS: Of the 35 of
      83 (42%) patients who were positive for OspA antigen in their CSF, 15 (43%) were
      antigen positive despite being antibody-negative in CSF. Seven of these 15 (47%)
      had otherwise normal routine CSF analyses. Six of these 15 (40%) patients met
      strict CDC surveillance criteria for Lyme disease; four (27%) patients had
      seroconversion coincident with new neurologic problems; and three (20%) with
      characteristic syndromes for Lyme disease were seronegative, but had complexed
      antibody to B burgdorferi. The final two patients (13%) were seropositive and had
      unexplained neurologic problems not characteristic of Lyme disease. CONCLUSIONS:
      B burgdorferi antigen can be detected in CSF that is otherwise normal by
      conventional methodology, and can be present without positive CSF antibody. Since
      CSF antigen implies intrathecal seeding of the infection, the diagnosis of
      neurologic infection by B burgdorferi should not be excluded solely on the basis
      of normal routine CSF or negative CSF antibody analyses.

PMID- 7501152
TI  - Clinical, electrophysiologic, and molecular correlations in 13 families with
      hereditary neuropathy with liability to pressure palsies and a chromosome 17p11.2
      deletion.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal
      dominant disease characterized by recurrent episodes of acute nerve palsies. We
      performed a clinical, electrophysiologic, and molecular study of 13 French
      families with HNPP associated with a chromosome 17p11.2 deletion in 36
      individuals. There were electrophysiologic abnormalities in all symptomatic (n =
      28) and asymptomatic (n = 8) deletion carriers, even in childhood. Bilateral
      delayed distal motor latency of the median nerve at the wrist, reduced sensory
      velocity in the palm-wrist segment, and delayed distal motor latency or reduced
      motor velocity in the peroneal nerve was diagnostic in at-risk relatives. This
      large series confirms the reliability of molecular analysis combined with a
      simplified electrophysiologic examination for the diagnosis of HNPP associated
      with 17p11.2 deletion.

PMID- 7501153
TI  - Abnormal sensory nerve conduction in multifocal demyelinating neuropathy with
      persistent conduction block.
AB  - Two patients exhibited chronic, slightly asymmetric weakness and wasting with
      fasciculations of the upper limb and hand muscles. Motor nerve conduction studies
      showed features of multifocal conduction block in nerve segments other than those
      usually involved in entrapment syndromes. The F wave was markedly delayed in the
      median and ulnar nerves. Transcranial cortical and cervical root magnetic
      stimulation showed bilaterally delayed thenar responses with normal central
      conduction time. Needle electromyography demonstrated a chronic denervation
      pattern with large polyphasic motor units in several muscles of the upper limbs.
      Sensory symptoms were mild and limited to paresthesias in the fingertips. Sensory
      nerve conduction velocity and sensory nerve action potential amplitudes were
      normal in elbow-to-wrist and wrist-to-finger segments of the median and ulnar
      nerves, but there was a delayed cortical response and unrecognizable Erb's point
      and cervical responses in the somatosensory evoked potentials to median nerve
      electrical stimulation. Electrophysiologic examination was normal in most nerves
      of the lower limbs. These two patients, meeting clinical and electrophysiologic
      criteria of multifocal neuropathy with conduction block, demonstrate that sensory
      fibers may also be involved in this syndrome.

PMID- 7501154
TI  - Differential response characteristics in nonepileptic and epileptic seizure
      patients on a test of verbal learning and memory.
AB  - Investigators have found it difficult to separate patients with nonepileptic
      seizures (NES) from those with true epileptic seizures (ES) using quantitative
      measures of neuropsychological test performance. We examined qualitative response
      characteristics on the California Verbal Learning Test of 41 patients undergoing
      continuous video/audio-EEG monitoring in an effort to distinguish these patient
      groups (12 patients with left temporal [LT] foci, 11 with right temporal [RT]
      foci, and 18 with NES). NES patients explicitly recognized fewer target words
      compared with ES patients. In addition, NES patients rarely made false-positive
      errors, which resulted in failure to endorse a significant number of items on the
      recognition list. This response tendency is called a negative response bias. In
      contrast, LT patients endorsed a high number of items on the recognition test,
      which resulted in a positive response bias. RT patients demonstrated no
      consistent response tendency. In our sample, a negative response bias index (ie,
      a cutoff score < 0) showed a sensitivity of 61% and a specificity of 91%. We
      propose that failure to explicitly recognize words following repeated exposure
      may reflect aspects of psychological denial in NES patients. Response bias
      indices may thus help identify patients with NES and may begin to explain the
      psychological mechanisms underlying this complex disorder.

PMID- 7501155
TI  - Is the stepping test a specific indicator of vestibulospinal function?
AB  - We studied the effect of walking on a horizontally rotating disk (circular
      treadmill) on the stepping test in seven normal subjects. Subjects walked for 2
      hours on the perimeter of the treadmill with eyes open while remaining stationary
      in space. Then, off the treadmill, they attempted to step in place with eyes
      closed for 50 paces without turning. All subjects exhibited post-treadmill
      turning in the same direction as that of the previous walking relative to the
      treadmill. Post-treadmill average angular velocities were 207 to 880 deg/min
      greater than pretreadmill values. No subject experienced any sensation of motion
      relative to ground or space. The stepping test may no longer be considered a
      specific indicator of vestibulospinal function.

PMID- 7501156
TI  - Variable clinical symptoms in familial amyotrophic lateral sclerosis with a novel
      point mutation in the Cu/Zn superoxide dismutase gene.
AB  - We report a novel missense point mutation in exon 4 of the Cu/Zn superoxide
      dismutase (SOD) gene of affected members of a Japanese kindred segregating
      familial amyotrophic lateral sclerosis (FALS) through at least three successive
      generations. The mutation, which is predicted to cause the replacement of
      isoleucine at codon 104 by phenylalanine (I104F), is associated with a
      significant reduction in Cu/Zn SOD enzyme activity but results in a highly
      variable clinical phenotype. Age at onset varied from 6 to 55; the initial
      symptoms occurred in either the lower or upper extremities in different family
      members. The duration of the disease varied from 3 to 38 years. Two subjects,
      aged 59 and 34, remained asymptomatic until their death from other causes,
      although their offspring carrying the same mutation have already developed
      clinical evidence of the disease. These results suggest that FALS from this novel
      I104F mutation shows considerable clinical variation.

PMID- 7501157
TI  - Prion disease (PrP-A117V) presenting with ataxia instead of dementia.
AB  - Gerstmann-Straussler-Scheinker disease (GSS) is caused by several different point
      mutations of the prion protein (PrP) gene, each of which generally produces a
      distinct clinical phenotype. An ataxic form of GSS is genetically linked to a
      mutation at codon 102 (CCG-->CTG) leading to the substitution of leucine for
      proline, while a "telencephalic" variant of GSS, in which dementia is the
      predominant symptom and ataxia is minimal, has been described in two kindreds
      with a mutation at codon 117 (GCA-->GTG) resulting in the substitution of valine
      for alanine. In this report, we present a family with ataxic GSS that has,
      however, the same mutation at codon 117 as is present in the telencephalic
      variant of GSS. Other than an additional silent mutation (GCA-->GCG) at codon 117
      on the normal allele, there were no other mutations detected. At the polymorphic
      codon 129, valine was encoded by both alleles in the proband that we studied. Why
      this family with prion disease (PrP-A117V) should present with ataxia instead of
      dementia, which was found in two previously identified families with the same PrP
      gene mutation, remains to be established.

PMID- 7501158
TI  - Seizure localization and pathology following head injury in patients with
      uncontrolled epilepsy.
AB  - We studied seizure localization and surgical pathology in 25 patients who
      developed intractable complex partial seizures following head trauma. All
      patients underwent an extensive presurgical evaluation that included MRI,
      neuropsychological evaluation, and surface EEG monitoring, and 21 had
      intracranial EEG monitoring. Seizures were successfully localized in nine
      patients; all nine underwent a surgical procedure and are seizure-free. Six of
      these patients had a mesial temporal lobe seizure focus, of whom five had a
      pathologic diagnosis of mesial temporal sclerosis. All five patients who
      developed mesial temporal sclerosis sustained their head injury at or before age
      5 years. The three remaining patients whose seizures were successfully localized
      had neocortical foci and circumscribed radiographic abnormalities, which were
      presumed to be secondary to head trauma, and all had successful surgical
      resections of the epileptogenic focus. The remaining 16 patients sustained later
      trauma, and all had successful surgical resections of the epileptogenic focus.
      The remaining 16 patients sustained later trauma and did not have a focal MRI
      lesion, and their seizures were not adequately localized. We conclude that as a
      group, seizure foci secondary to head trauma are difficult to localize
      accurately, and this should deter surgical intervention. There was an association
      between early head injury (ie, at or before age 5 years) and mesial temporal
      sclerosis, and this association aided seizure localization and successful
      surgical intervention. Therefore, under the right circumstances, trauma can be a
      suitable historical element in the profile of patients in whom epilepsy surgery
      is successful.

PMID- 7501159
TI  - Frequency and characteristics of dual pathology in patients with lesional
      epilepsy.
AB  - We studied 167 patients who had identifiable lesions and temporal or
      extratemporal partial epilepsy. Pathology included neuronal migration disorders
      (NMDs) (48), low-grade tumors (52), vascular malformations (34), porencephalic
      cysts (16), and gliotic lesions as a result of cerebral insults early in life
      (17). MRI volumetric studies using thin (1.5- or 3-mm) coronal images were
      performed in all patients and in 44 age-matched normal controls. An atrophic
      hippocampal formation (HF), indicating dual pathology, was present in 25 patients
      (15%). Abnormal HF volumes were present in those with lesions involving temporal
      (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy
      did not influence the presence of HF atrophy. However, febrile seizures in early
      childhood were more frequently, although not exclusively, found in patients with
      hippocampal atrophy. The frequency of hippocampal atrophy in our patients with
      low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far
      more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive
      gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be
      associated with hippocampal atrophy, independent of the distance of the lesion
      from the HF. In other types of lesions, such as vascular malformations, dual
      pathology was found when the lesion was close to the HF. A common pathogenic
      mechanism during pre- or perinatal development may explain the occurrence of
      concomitant mesial temporal sclerosis and other structural lesions because of
      either (1) associated developmental abnormalities or (2) predisposition to
      prolonged febrile convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501160
TI  - Saccadic duration and intrasaccadic fatigue in myasthenic and nonmyasthenic
      ocular palsies.
AB  - We measured the duration and amplitude of saccades in three normal subjects,
      eight patients with myasthenia gravis, and eight patients with nonmyasthenic
      ocular palsies. Saccades were examined at the start of a repetitive saccade task,
      after 3 minutes of activity, and 1 minute after administration of edrophonium.
      The duration of saccades was prolonged initially in both myasthenic and
      nonmyasthenic palsies. Activity did not produce significant differences among the
      three groups in either the slope of the duration-amplitude relationship or the
      predicted durations of saccades of 5 degrees, 10 degrees, or 15 degrees. However,
      durations decreased in myasthenia but increased in nonmyasthenic palsies after
      edrophonium. Much of this decrease in myasthenic saccadic duration was due to
      reduction in deceleration time, indicating resolution of intrasaccadic fatigue
      after edrophonium administration. However, the relation of deceleration fraction
      (deceleration time divided by total duration) to total duration remained constant
      in all subject groups. Analysis of saccadic duration is a useful means of
      interpreting responses to edrophonium because it incorporates data from saccades
      of a wide range of amplitudes into a linear relation between duration and
      amplitude.

PMID- 7501161
TI  - Horizontal canal benign paroxysmal positioning vertigo: reversible ipsilateral
      caloric hypoexcitability caused by canalolithiasis?
AB  - Bithermal caloric stimulation in a patient with a benign paroxysmal positioning
      vertigo of the horizontal (lateral) semicircular canal (HC-BPPV) revealed a
      significant hypoexcitability of the affected ear that was reversible when treated
      by liberatory maneuvers. Both the positional vertigo and caloric hypoexcitability
      in HC-BPPV are caused by canalolithiasis, a concept strongly supported by the
      intensity of the positioning nystagmus being maximal when the patient turned his
      head around the longitudinal z-axis from the left lateral to right lateral
      position while recumbent (maximum slow-phase velocity [SPV] 176 deg/sec) and
      being much lower (maximum SPV 55 deg/sec) when he turned his head to the right
      lateral position while in a supine position (nose up). The dependence of this
      difference in nystagmus intensity on the initial head position and direction of
      rotation indirectly proves that the clot moves freely (to and fro) within the
      segment of the HC diametrically opposite to the ampulla. The reversibility of
      ipsilateral caloric hypoexcitability is attributed to the clot's (functional)
      plugging of the HC, which agrees with studies in squirrel monkeys. These data
      support the view that physiologic caloric responses consist of a major convective
      and minor nonconvective component.

PMID- 7501162
TI  - The effect of white matter hyperintensity volume on brain structure, cognitive
      performance, and cerebral metabolism of glucose in 51 healthy adults.
AB  - OBJECTIVE: To assess the association of MRI white matter hyperintensities (WMHI)
      with cognitive performance, cerebral structure, and cerebral metabolism in 51
      healthy individuals aged 19 to 91 years without cerebrovascular risk factors.
      BACKGROUND: Abnormal white matter signals have been associated with brain
      atrophy, reduced cerebral blood flow, focal neurologic signs, gait disorder, and
      poorer neuropsychological test performance. Most studies of WMHI, however,
      include subjects with hypertension or other identifiable causes of
      cerebrovascular disease that may have an independent effect on brain structure
      and function. To assess brain changes associated with WMHI independent of
      cerebrovascular risk factors, we determined WMHI volume, brain volume, cerebral
      metabolism, and cognitive performance for a group of subjects free of medical
      illness. Regional cerebral metabolism and cognitive domains were also assessed to
      evaluate the possible role of frontal lobe dysfunction in subjects with WMHI.
      DESIGN: Cross-sectional study of 51 very healthy subjects aged 19 to 91 years.
      METHODS: WMHI, brain, and CSF volumes were determined by MRI segmentation.
      Neuropsychological tests were employed to assess multiple cognitive domains.
      Brain metabolism was determined from 18-fluoro-2-deoxy-D-glucose PET.
      Multivariate relations were tested with stepwise linear regression. Models
      included the potential confounders of age and education where appropriate.
      RESULTS: The distribution of WMHI volume was bimodal, with five subjects having
      WMHI volumes beyond three SDs from the normally distributed population. A WMHI
      volume of greater than 0.5% of intracranial volume was considered abnormal.
      Within the multivariate models, WMHI volumes were significantly predictive of
      increased ventricular volume, reduced brain volume, and reduced cognitive scores.
      Subjects with greater than 0.5% WMHI volume also had significantly lower frontal
      lobe metabolism, significantly higher systolic blood pressure, significantly
      larger ventricular volume, and significantly lower scores on frontal lobe
      mediated neuropsychological tests than age-matched controls. CONCLUSION: WMHI
      volume is associated with structural and functional brain changes even within a
      group of very healthy individuals. WMHI is associated with poorer frontal lobe
      cognitive function and, when severe, is accompanied by significantly reduced
      frontal lobe metabolism. Subjects with large WMHI volumes have significantly
      higher systolic blood pressure, brain atrophy, reduced cerebral metabolism, and
      lower scores on tests of frontal lobe function than age-matched controls. Large
      amounts of WMHI are, therefore, pathologic and may be related to elevated
      systolic blood pressure even when it is within the normal age-related range.

PMID- 7501163
TI  - Merosin-negative congenital muscular dystrophy associated with extensive brain
      abnormalities.
AB  - Congenital muscular dystrophies (CMDs) are autosomal recessive, heterogeneous
      disorders. The most frequent form in the Caucasian population is classic
      (occidental) CMD, characterized by exclusive muscle involvement, although
      abnormal brain white matter signals are occasionally observed on MRI. Recently,
      deficiency of merosin, the laminin isoform in skeletal muscle, has been
      identified in classic CMD patients. In skeletal muscle, merosin is a native
      ligand for dystroglycan linking the extracellular matrix and dystrophin. Thus,
      merosin deficiency could disrupt the attachment of muscle cell to the
      extracellular matrix and lead to muscle cell necrosis. Since merosin is also
      expressed in the nervous system and has biologic activities on neurite outgrowth
      and Schwann cell migration, deficiency of merosin could affect the development of
      the nervous system. We report here two patients with merosin-negative CMD
      presenting extensive brain abnormalities characterized by cortical anomaly,
      polymicrogyria, and abnormal white matter signals.

PMID- 7501164
TI  - Clinical variability in two pairs of identical twins with the Charcot-Marie-Tooth
      disease type 1A duplication.
AB  - We report two pairs of male homozygotic twins in two unrelated families with the
      Charcot-Marie-Tooth disease type 1A duplication. Homozygosity was supported by
      DNA analysis. There was remarkable congruity of conduction velocities between the
      left and right side of each twin and between twin brothers. The similarity and
      symmetry of the electrophysiologic deficit contrast with the variable and
      asymmetric clinical presentations. Variability of clinical expression in these
      patients with identical mutations suggests the action of stochastic factors or
      environmental modulation of disease severity.

PMID- 7501166
TI  - Generalized mitochondrial dysfunction in Parkinson's disease detected by magnetic
      resonance spectroscopy of muscle.
AB  - OBJECTIVE: To explore mitochondrial dysfunction in Parkinson's disease (PD) using
      31P magnetic resonance spectroscopy of resting muscle. DESIGN: Case-control study
      (28 PD patients and 28 normal controls) determining resting forearm inorganic
      phosphate/phosphocreatine (Pi/PCr) ratio. RESULTS: Significant difference (p =
      0.004, one-tailed test) in Pi/PCr ratio between PD patients (0.122) and controls
      (0.104). No correlation of Pi/PCr ratio with duration, severity, or speed of
      onset of disease. Positive correlation of Pi/PCr ratio with age in control group;
      reversed in PD group. CONCLUSIONS: Suggests small generalized mitochondrial
      defect in PD. The possibility that earlier onset of disease is associated with
      more severe mitochondrial dysfunction needs further study.

PMID- 7501165
TI  - Site of autonomic dysfunction in a patient with Ross' syndrome and postganglionic
      Horner's syndrome.
AB  - Ross' syndrome is a rare peripheral nervous system disorder defined by Adie's
      tonic pupil, hyporeflexia, and segmental anhidrosis. Injury to postganglionic
      cholinergic fibers is believed to account for the tonic pupil and sweating
      disturbance. We report a 47-year-old man found to have Ross' syndrome in
      combination with a complete postganglionic Horner's syndrome. Pharmacologic and
      sudomotor tests in this unique patient provide further evidence that Ross'
      syndrome results from injury to sympathetic and parasympathetic ganglion cells or
      to their postganglionic projections.

PMID- 7501167
TI  - Laminin beta 2 chain and adhalin deficiency in the skeletal muscle of Walker
      Warburg syndrome (cerebro-ocular dysplasia-muscular dystrophy).
AB  - Muscular dystrophy may be caused by disturbances in a number of muscle proteins
      that appear to be part of a chain of interacting molecules that includes
      cytoskeletal, cell membrane, and basement membrane components. We found that the
      skeletal muscle cells in two cases of Walker-Warburg syndrome were severely
      deficient in the laminin beta 2 chain and in adhalin. The findings indicate that
      these two proteins are key molecules in the interactive protein complex
      conferring muscle stability and cell survival.

PMID- 7501168
TI  - Charcot as therapeutic interventionist and treating neurologist.
AB  - Although Jean-Martin Charcot's best-known medical and scientific contributions
      relate to anatomical-clinical correlation, he was also a highly regarded
      physician. His published lectures and articles, as well as documents at the
      Bibliotheque Charcot, demonstrate his active interest in therapeutic
      interventions and in bringing new experimental treatments to France for study. He
      investigated the efficacy of bromides for epilepsy, colchicine for gout, and
      ergots and anticholinergic drugs for Parkinson's disease. Nonpharmacologic
      treatments in which he took interest included physical rehabilitation/speech
      therapy, hydrotherapy, electrical stimulation of weakened muscles, isolation, and
      exotic interventions such as suspension and vibratory treatments with special
      chairs and helmets. Letters from his patients reveal an active interchange, with
      patients complimenting Charcot on successful treatments but also demanding more
      effective ones when his prescriptions did not abate their conditions. These
      documents demonstrate that Charcot was not a therapeutic nihilist but was
      particularly active in therapeutic investigations in the context of 19th-century
      medical science.

PMID- 7501169
TI  - Botulinum toxin type B in the treatment of cervical dystonia: a pilot study.

PMID- 7501170
TI  - Intrathecal L-baclofen for cerebral spasticity: case report.

PMID- 7501171
TI  - Parkinsonism secondary to petroleum exposure.

PMID- 7501172
TI  - Dementia in the elderly.

PMID- 7501173
TI  - Tardive pain.

PMID- 7501174
TI  - Tardive pain.

PMID- 7501175
TI  - Manganism.

PMID- 7501176
TI  - Manganism.

PMID- 7501177
TI  - Vasomotor reactivity.

PMID- 7501178
TI  - Vigabatrin edema.

PMID- 7501179
TI  - Nonsteroidal anti-inflammatory drugs in Alzheimer's disease.

PMID- 7501180
TI  - Chronic whiplash syndrome.

PMID- 7501181
TI  - Chronic whiplash syndrome.

PMID- 7501182
TI  - Chronic whiplash syndrome.

PMID- 7501183
TI  - Chronic whiplash syndrome.

PMID- 7501184
TI  - Balint's syndrome.

PMID- 7501185
TI  - Triglycerides and neuropathy.

PMID- 7501186
TI  - Neuronal migration disorders.

PMID- 7501187
TI  - Paraneoplastic antibodies.

PMID- 7501188
TI  - Midbrain vascularity.

PMID- 7501189
TI  - Triage of American combat casualties.

PMID- 7501190
TI  - About TRICARE.

PMID- 7501191
TI  - Septicemia due to contaminated intravenous fluids: a point to remember.

PMID- 7501192
TI  - Environmental health issues in prisoner of war camps.
AB  - Maintaining adequate environmental health and sanitation conditions in prisoner
      of war camps is essential for the fulfillment of our international legal
      obligations under the Geneva Conventions. Insights from Desert Storm and other
      conflicts are discussed.

PMID- 7501193
TI  - A patient satisfaction survey: a basis for changing delivery of services.
AB  - Through a collaborative effort with Kansas State University's Institute for
      Social and Behavioral Research, a marketing health care needs survey was
      conducted at Irwin Army Community Hospital prior to the implementation of
      coordinated care. The objectives of this survey were: (1) determine household
      health care program eligibility; (2) measure usage, perceptions, and barriers in
      our health care system; and (3) gauge interest in prospective changes or new
      programs. Using the results of this survey, valuable information was obtained for
      strategic planning and new programs were developed with the needs of our
      population in mind.

PMID- 7501194
TI  - The Occupational Health Partnership Program: a new paradigm for occupational
      health services.
AB  - For a variety of reasons, occupational health services at Army Material Command
      installations became severely strained during the 1980s. The Occupational Health
      Partnership Program, developed to improve this support, describes control,
      responsibility, and cost sharing between Army Materiel Command and Army Medical
      Command. This innovative approach is finding new solutions to challenging
      problems. The authors describe the history, principles, status, and possible
      future of the partnership program.

PMID- 7501196
TI  - Compensation and pension evaluations: psychotic, neurotic, and post-traumatic
      stress disorder Millon Clinical Multiaxial Inventory II profiles.
AB  - The purpose of the present work was to provide an examination of the three major
      VA adjudication classifications (post-traumatic stress disorder [PTSD],
      psychotic, and neurotic) through objective psychological testing. During routine
      follow-up compensation and pension evaluations, 143 patients were given the
      Millon Clinical Multiaxial Inventory II (MCMI-II). Additionally, their current
      disability diagnoses as well as their current percentage of disability were
      coded. Discriminant function analysis revealed that the pivotal discriminatory
      variables were alcohol abuse for the PTSD patients, thought disorder for the
      psychotics, and anxiety for the neurotics. This is remarkably consistent with
      general clinical expectations. This should allow for more specific use of the
      MCMI-II in compensation and pension examinations by Department of Veterans'
      Affairs psychologists.

PMID- 7501195
TI  - A review of United States Air Force aeromedical evacuation of acute myocardial
      infarction patients in Europe.
AB  - United States Air Force regulations currently do not recommend the routine
      movement of recently stabilized patients diagnosed with acute myocardial
      infarctions. However, U.S. Department of Defense and embassy physicians
      throughout Europe continually request aeromedical movement of these patients.
      Therefore, a year-long prospective case review of acute myocardial infarction
      (AMI) patient movement within the military aeromedical system in Europe was
      undertaken to evaluate the need for and safety of transporting these patients.
      This case review, combined with the literature, suggests that recently stabilized
      AMI patients, with appropriate pre-flight preparation and in-flight care, can
      tolerate exposure to the stresses of flight and can be safely airlifted.

PMID- 7501197
TI  - Individual Mobilization Augmentation: recipe for an effective total force
      partnership.
AB  - The ability to carry out rapid mobilization and full integration of well-trained
      reserve/guard personnel with active component personnel proved to be a decisive
      factor during the Gulf War. Such an approach can also be effective in fulfilling
      peacetime military missions, especially in an environment of increasing
      requirements, nontraditional missions, and pervasive force reductions. This paper
      describes the role played by Army Reserve Individual Mobilization Augmentation
      (IMA) assets in support of two important Army Medical Department missions
      involving new initiatives in scientific peer review and extramural grant
      administration: military nursing research and breast cancer. Successful planning,
      development, and implementation of these programs is attributed in part to the
      fostering of an effective partnership between reserve and active components on
      both individual and organizational levels. Critical factors influencing this
      partnership are analyzed and the relevance of such peacetime IMA taskings to
      wartime missions is discussed.

PMID- 7501198
TI  - Army family physician satisfaction.
AB  - INTRODUCTION: As numbers of family physicians decrease in the Army, the Army
      needs to know how satisfied they are with being family physicians and military
      officers. What variables are associated with these satisfactions? METHODS: This
      was a cross-sectional mailed survey of Army family physicians (N = 334). The
      response rate was 82% (N = 274). The survey included questions with a Likert
      scale and was analyzed using Kruskal-Wallis, one-way analysis of variance, and
      logistic regression. RESULTS: Ninety-two percent were satisfied with being family
      physicians and 74% were satisfied with being military officers. The variables
      associated with satisfaction were rank (positively associated) and percent time
      in patient care (negatively associated). CONCLUSIONS: Army family physicians are
      more satisfied with being family physicians than they are with being military
      officers. They are, however, satisfied with both professions. The Army, as an
      organization, may want to explore how its system of rewards interplay with rank
      and amount of time in patient care to make them predictive of satisfaction.

PMID- 7501199
TI  - Persian Gulf illnesses: preliminary neurological impressions.
AB  - We review the initial impressions of the first 65 patients evaluated
      neurologically at Madigan Army Medical Center as mandated by the Comprehensive
      Clinical Evaluation Program of the Department of Defense for Persian Gulf
      veterans. No consistent patterns of neurologic disease or new neurologic
      syndromes emerged. Our experience suggests that full neurological evaluation of
      such patients without a clear history of neurological symptoms is not cost
      effective. Headaches and sleep difficulties were the two most frequent
      complaints. We suggest that sleep disorders may be underdiagnosed in active duty
      populations.

PMID- 7501201
TI  - Twenty commonly dispensed medications at a United States military installation
      and their significance to dentists.
AB  - Understanding the clinical pharmacology of medications commonly used by dental
      patients is necessary when providing dental care. A significant number of
      patients may be taking medications that have the potential for adverse effects.
      The purpose of this paper is to familiarize dental practitioners with the
      clinical pharmacology of medications most likely to be encountered in a current
      military dental practice. Product activity reports (records of medications usage)
      were obtained from the main pharmacy at a United States Army Community Hospital.
      The product activity reports covered a 1-year period from December 31, 1992, to
      December 30, 1993. These reports were analyzed according to the number of
      medications dispensed to determine the 20 most commonly used medications.

PMID- 7501200
TI  - Ambulatory mental health services at a U.S. Army combat support post: the effects
      of the Persian Gulf War.
AB  - A study of ambulatory mental health services on a U.S. Army post where logistic
      support personnel are stationed compared utilization of psychiatric services
      before, during, and after the Persian Gulf War. Rates were calculated for service
      utilization for the at-risk groups from consecutive cases presenting at the
      post's ambulatory mental health services in the Department of Psychiatry. Our
      findings include a high rate of dysfunction for soldiers in training during the
      war; significant age, race, and sex differences between utilizers and non
      utilizers throughout the study period; increased routine evaluations for military
      schools following the war; and significant increases in utilization of services
      by identified high-stress units during this conflict. Rates of utilization for a
      combat support post can be used for resource allocation and have implications for
      mental health manpower planning and stress prevention.

PMID- 7501202
TI  - The evolution of American Medical Association policies concerning health care of
      veterans.
AB  - Relationships between the American Medical Association (AMA) and the Department
      of Veterans Affairs (VA) have been reviewed from the perspective of evolving AMA
      policies regarding the care of veterans, including educational and research
      policies. During the first two decades of VA hospital development between 1925
      and 1945, the AMA opposed government participation in the care of veterans.
      During the next three decades there was a reluctant acknowledgement by the AMA of
      the need for federally housed care of veterans with service-connected illnesses.
      At the same time, the AMA recognized the value of the mission of the VA in
      training specialists through postgraduate medical education. More recently the
      AMA has been especially supportive of VA-medical school affiliations and VA
      activities in education and research. The reluctance of the AMA to support
      veterans' health care was paralleled by reluctance of VA staff physicians to join
      the AMA. In recent years the AMA has recognized the need to diversify its
      membership as increasing numbers of physicians have been trained in part in VA
      medical centers. It appears to be a time of enhanced opportunity for the AMA to
      work more closely with the Department of Veterans Affairs.

PMID- 7501203
TI  - Self-care styles in military veterans.
AB  - Understanding of self-care behaviors in veterans has been hampered by lack of a
      framework by which to describe styles or patterns of individual self-care. The
      primary purpose of this study was to identify consciously performed health
      practices in 69 U.S. military veterans and to categorize these behaviors into
      styles. Four categories of self-care were described based on the nature and
      extent of health concerns addressed by individual health regimens and on the
      types of resources utilized. Membership in the various categories was not related
      to age, sex, race, or health status of veteran subjects, but was significantly
      related to scores on Kearney and Fleischer's Exercise of Self-Care Agency
      Instrument.

PMID- 7501205
TI  - Second trimester uterine atony imitating ectopic pregnancy: magnetic resonance
      diagnosis.
AB  - When an obstetrical patient was referred for inability to auscultate fetal heart
      tones at 18 weeks' gestation, ultrasound identified a single living fetus in the
      maternal right upper quadrant. Magnetic resonance imaging (MRI) ruled out a
      suspected uterine ectopic pregnancy and avoided laparotomy. The patient
      experienced an uncomplicated term delivery. MRI is a useful adjunct to ultrasound
      for mid-trimester pregnancy localization when the differential diagnosis includes
      uterine eccyesis.

PMID- 7501204
TI  - Effects of reduced fat intake on serum lipids in healthy young men and women at
      the U.S. Military Academy.
AB  - To assess the benefits of Army nutrition initiatives reducing intakes of fat and
      cholesterol, the authors studied the dietary intakes of cadets at the U.S.
      Military Academy and compared these results and related nutritional indicators
      (body composition, serum lipid status) to data obtained one decade earlier. The
      regular Cadet Mess menu provided 16.6 MJ/day of energy with 34% derived from fat.
      Actual intakes, including supplements, averaged 14.9 +/- 2.9 and 9.7 +/- 2.1
      MJ/day for 119 male and 86 female cadets, respectively. Most cadets derived < 35%
      of energy from dietary fat (11% from saturated fatty acids), representing a
      significant reduction since the previous study, in which nearly one-third of
      cadets received 40 to 45% of calories from fats; cholesterol intakes were
      markedly reduced. Serum cholesterol levels were approximately 7% lower, but were
      less affected than predicted by the reductions in fat and cholesterol intakes;
      serum low-density lipoprotein-cholesterol was also significantly reduced. Fasting
      serum insulin correlated with saturated fat intake in female cadets, indicating
      another health risk factor affected by intakes. The authors conclude that
      nutrition initiatives reducing energy derived from fats and total cholesterol
      intake have had a beneficial effect on the nutritional status of this fit young
      population.

PMID- 7501206
TI  - Contact urticaria to the M17 protective mask.
AB  - A case of contact urticaria to a compound used in the production of the M17
      protective mask is reported. The new M40/42 series protective mask has a
      different composition, and should be tried as an alternative to the M17 mask in
      service members with black rubber allergies.

PMID- 7501207
TI  - Pulmonary scar carcinoma: report of three cases and review of the literature.
AB  - Pulmonary scar carcinoma was described as a distinct clinicopathological entity
      over 50 years ago. There are many theories on the formation of this entity. We
      present three cases of pulmonary scar carcinoma with a high ratio of
      adenocarcinoma. One patient had a favorable postoperative course despite a 14
      month delay in treatment. Necropsy specimen of another patient showed two primary
      scar carcinomas unrelated to each other. Literature review and discussion of
      etiology, diagnosis, and treatment modalities of pulmonary scar carcinoma were
      done. Pathogenesis and prognosis of the neoplasms associated with apical scars
      are not clearly understood.

PMID- 7501208
TI  - [Early gastric cancer].
AB  - The authors perform a retrospective analysis of 46 cases of EGC referred to the
      Surgical Division of Carrara Civic Hospital during the period 1980-1990 who
      subsequently underwent surgery. Data relating to age, symptomatology and
      endoscopic examinations were analysed in order to evaluate the real diagnostic
      penetration of the method in association with tumour biopsy, site, macroscopic
      aspect, possible lymph node involvement and the histology of lesions. The most
      frequent form of surgery in this series was subtotal gastrectomy and the 5- and
      10-year survival rates, calculated using an actuarial method, were compared with
      data reported in the literature. The authors conclude by emphasising the need to
      improve the frequency of diagnosis of gastric cancer at an "early" stage and
      affirm that gastric resection associated with lymphoadenectomy of 1st and 2nd
      level lymph nodes is a sufficiently radical operation and less punitive for the
      patient compared to total gastrectomy given that the 5- and 10-year survival
      rates are comparable.

PMID- 7501209
TI  - [Vascularization of the gastric stump tubule in esophagogastroplasty (EGP)].
AB  - The authors present the results of the vascular supply of tubulized gastric stump
      in patients who had sub-total oesophagectomy and cervical oesophago-gastroplasty
      (OGP) for oesophageal carcinoma, evaluating the importance of altered tubulized
      gastric stump's vascular supply on oesophago-gastric anastomosis efficiency. From
      April 1989 up today 51 patients who had OGP entered this study. Among these 2 had
      intestinal reconstruction by whole stomach and 49 by tubulized gastric stump.
      These 49 patients had celiac and upper mesenteric arterial angiography 30 days
      after surgery. As regards vascular patency angiography allowed us to divide the
      tubulized gastric stump into three parts; giving useful information above all on
      the distal part of the stump, considered "at risk" as concerning vascular supply.
      The authors thus demonstrate that the anastomosis high rate dehiscence is
      preferably due to the oesophageal stump vascular supply (strongly affected by
      cervical dissection) rather than to the poor vascular supply of the distal third
      of the transposed tubulized gastric stump.

PMID- 7501210
TI  - [Laparoscopic treatment of Mirizzi's syndrome].
AB  - The Mirizzi syndrome is an unusual benign obstructive jaundice due to extrinsic
      mechanical compression of the common hepatic duct by gallstone impacted within
      the neck or cystic duct of the gallbladder. This syndrome is described either as
      an acute form due only to extrinsic compression of the common bile duct (type I)
      or as a chronic form resulting in an erosive cholecysto-choledochal fistula (type
      II). Up to date, the syndrome remains a clinically and surgically challenging
      problem. The anatomic basic of the syndrome (an anomalous relationship between
      the cystic duct and the common hepatic duct) when associated with inflammation
      and interbiliary fistula predisposes to a critical situation to be clearly
      detected and contributes to technical difficulties when surgical management is
      performed. The operative diagnosis of Mirizzi syndrome remains elusive and
      requires careful scrutiny of the biliary tract imaging to recognize the diseased
      duct system and to facilitate the following operative procedures. The surgical
      treatment requires a skill and careful operative dissection of the duct system,
      cholecystectomy and a safe biliary exploration and stone clearance, avoiding any
      iatrogenic damage to common hepatic duct. Laparotomy is commonly advocated as the
      safer approach to the diseased biliary tract and it is still employed by most
      authors. The laparoscopic surgery has not yet entered as the first-choice
      procedure for this syndrome due to jaundice and acute inflammation considered by
      some as contraindication to mini-invasive treatment. This paper describes
      successful surgical management by laparoscopic techniques in two patients
      affected by Mirizzi type I and type II syndrome treated by cholecystectomy alone
      and cholecystectomy with choledochal fistula flap repair, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7501211
TI  - [Pilonidal cysts and fistulas: radical excision "en bloc" and closure "per
      primam"].
AB  - For the radical surgical treatment of pilonidal cysts and fistulas, the authors
      suggest the excision "en bloc" of the complete pathological tissue and the
      primary closure, according to a procedure which considers not only a accurate
      surgical technique and a kind of dressing which avoids pressure and traction on
      the sutures, but also a s.t. antibiotic prophylaxis based on culture tests. This
      kind of approach in surgical treatment showed according to their experience,
      excellent immediate and long term results, causing slight inconvenience to
      patients, with a short recovery with regard to cases treated without primary
      closure.

PMID- 7501212
TI  - [Skin tumors. Localization of basal cell carcinoma in 162 patients].
AB  - The authors present a study on the incidence of skin tumors of the face. Benign
      tumors are important both from an aesthetic point of view and also because some
      precancerous lesions may degenerate. Major emphasis is placed on the various
      aspects of malignant lesions: basal cell carcinomas prevail in the more exposed
      areas of the face. The various surgical techniques in managing facial tumors are
      presented and discussed, underlining the importance of both oncological
      radicality and functional and aesthetic aspects.

PMID- 7501214
TI  - [Treatment of leg ulcers with fibrin glue].
AB  - The work is based on two years studied cases. It consists of 80 patients between
      35 and 80 years old with leg ulcers (73.8% women and 26.2% men). In 80% of
      patients this affection is due to a venous disease. In 10% of cases the cause was
      an arterial insufficiency of the lower extremity. Lymphatic and extravascular
      diseases are rarely involved. A group of 54 patients was treated with a
      traditional method. In the remaining 26 patients we used fibrin glue. Leg ulcers
      are an evolutive chronic pathology characterized by slow recovery. This means
      expensive social and therapeutic costs. From this point of view the treatment
      with fibrin glue, weekly applied, besides reducing pain, has a favourable impact
      on the outcome, times of re-epithelialization are shortened.

PMID- 7501213
TI  - [Use of polypropylene (Marlex) prosthesis in the surgical treatment of inguinal
      and crural hernia].
AB  - High biocompatibility, low cost and easiness in use are most important reasons
      for the spread of biological prosthesis in inguinal and femoral hernia repairs;
      this fact has changed the surgical approach to this kind of pathologies. This new
      approach consists in re-creating a normal anatomic function of the abdominal
      wall, without new tension between muscles and aponeurotic structures. The authors
      present their experience after 379 inguinal and femoral hernia repairs between
      January 1992 and December 1993.

PMID- 7501215
TI  - [Spontaneous transmural rupture of the esophagus (Boerhaave's syndrome)].
AB  - A case is presented of spontaneous transmural rupture of the lower third of the
      esophagus, penetrating the left pleural space. The patient underwent repair under
      7 hours by combined approach (laparotomy and left thoracotomy). High mortality
      and morbidity of Boerhaave's syndrome can be lowered by prompt and careful
      evaluation of symptoms and radiological signs, so avoiding incorrect or late
      diagnosis. Results appear to be related more to the time interval between
      perforation and operation than to the specific technique used.

PMID- 7501216
TI  - [Rupture of the duodenum caused by closed abdominal trauma].
AB  - A duodenal lesion due to blunt abdominal trauma is an infrequent eventi which
      makes important diagnostic and therapeutic problems. The preoperative diagnosis
      is not always easy, especially with retroperitoneal lesion or in injured
      patients. A plain abdominal radiography or a duodenal radiography with soluble
      contrast medium helps to achieve a proper diagnosis. Prognosis strictly depends
      on time between injury and surgical procedures. We report two successfully
      treated lesions of fourth duodenal due to a blunt abdominal trauma.

PMID- 7501217
TI  - [A rare case of Meckel's diverticulum perforation].
AB  - Meckel's diverticulum is a pathology not rarely found everyday clinical medicine
      especially when it present with one of its complications. The specific diagnosis
      is a bit difficult to put because of the low sensibility and specificity of
      symptoms of diagnostic and instrumental techniques used. The reported case shows
      a rare type of complication constituted by the phlogosis of Meckel's
      diverticulum, itself due to an extraneous thing ingested by the patient. The
      authors discuss the entity of the manifestations of this pathology and highlight
      every aspects.

PMID- 7501218
TI  - [Adhesive peritonitis caused by a foreign body. A case report].
AB  - After investigation of the international literature on this subject, the authors
      describe a case report of adhesive-stenotic and retractile peritonitis, very
      likely caused bt a foreign body reaction (surgical stitches, gloves, rice powder,
      etc.?). This case-report is interesting both to remember the existence of this
      pathology and to limit its iatrogenic development. In conclusion, it is advisable
      to wash surgical gloves with sterile solutions and to limit enlarged bowel
      resections mostly in young people.

PMID- 7501219
TI  - [Leiomyosarcoma of the mesenteric root. A case report].
AB  - Although smooth muscle tumors are the most common mesentery neoplasms, they are
      lesions of infrequent occurrence. The main clinical features of these
      malignancies are an insidious onset and an aspecific symptomatology, usually
      presenting themselves as quite large masses. The preoperative diagnosis is
      difficult, but selective angiography and CT scan may be of great value for this
      purpose. Since these malignancies are usually not responsive either to
      radiotherapy or chemotherapy, once diagnosed, the only hope of cure lies in
      surgical resection. The authors report case of leiomyosarcoma of the mesentery
      root, treated with radical surgery and still alive and disease free 12 months
      after resection.

PMID- 7501220
TI  - [Monolateral renal angiomyolipoma: a case of Wunderlich's syndrome].

PMID- 7501221
TI  - [Retroperitoneal leiomyosarcoma originating from the inferior vena cava. A case
      report].
AB  - After a brief review of the literature, the authors report a rare case primitive
      retroperitoneal leiomyosarcoma originating from the inferior vena cava. The tumor
      was diagnosed very early thanks to its early symptoms and signs (abdominal pain
      and palpability), which appeared when the tumor size was only 5 cm. Therefore it
      was possible a macroscopically radical surgical exeresis even if the anatomical
      situation was particularly delicate. The low grading and staging of the tumor
      allowed to express a positive prognosis in spite of the malignant nature of this
      sarcoma.

PMID- 7501222
TI  - [Use of mechanical staplers in colorectal resections. Personal experience].
AB  - Staplers have introduced and continue to introduce benefits above all in terms of
      anastomotic procedures used in digestive tract surgery. A prime sector od
      application is rectal cancer in that mechanical anastomosis allows low rectal
      resections to be performed, thus reducing the number of abdominoperineal
      amputations, without negatively affecting the oncological radicality of exeresis.
      The authors review the cases operated by the 1st Chair of Surgical Pathology at
      "La Sapienza" Rome University during the period 1984-1993 when rectal anastomoses
      were systematically performed using mechanical staplers. On the basis of their
      personal experience and in line with the data reported in the literature,
      although there may be anastomotic complications, such ad dehiscence ad stenosis,
      it is possible to affirm that the use of staplers has led to benefits which, if
      evaluated as a whole, fully justify their cost which is still quite considerable.

PMID- 7501223
TI  - [In vivo experimental research in vascular surgery. Methodology and current
      Italian law].
AB  - Authors underscore the importance of research in vascular surgery progress and
      approach some basic aspects on the correct conduction of an experimental research
      in vascular surgery fields and in particular on synthetic prosthesis of different
      diameter. Some important aspects of the current Italian law on animal
      experimentation are shown because they could cause new changes either on
      methodology or animal selection. Finally some experimental models adopted in the
      department of experimental surgery of the Rizzoli Orthopaedic Institutes on
      vascular prosthesis are described.

PMID- 7501225
TI  - [The resistance of activated partial thromboplastin time to heparin infusion
      during hemodialysis].
AB  - Activated partial thromboplastin time (aPTT) during heparin infusion in 10
      patients on regular dialytic treatment was evaluated. At end-dialysis (3 hours)
      plasma heparinization ranged between 2000-4000 IU and from the clinical point of
      view dialytic performance was good. At end-dialysis aPTT was 53 +/- 14 seconds:
      this value is under the prescribed aPTT prolongation (1.5-2 times baseline
      values) to achieve a therapeutic heparin plasma level. Physiopathological
      implications of this aPTT "resistance" to heparin infusion are studied.

PMID- 7501224
TI  - Community-acquired pneumonia: is there difference in etiology between
      hospitalized and out-patients?
AB  - Since March 1991 a prospective 1-year study of patients with community-acquired,
      radiologically verified, pneumonia (CAP) was performed at the Divisione
      Pneumologica, Ospedali Riuniti Bergamo, and at the Centro Pneumo-Allergologico,
      Bergamo, Italy. The study included 119 out-patients and 60 in-patients, with a
      median age of 37.4 and 49.8 years respectively. There were not statistically
      significant differences between the patients included with respect to the various
      months. The most common underlying illnesses were: chronic obstructive pulmonary
      disease (20.7%), diabetes (7.3%) and malignancy (3.4%). We found a quite
      different etiology of CAP between out- and in-patients. By far the most common
      etiologic agent in out-patients was Mycoplasma pneumoniae (32.8%), while in in
      patients was Legionella pneumophila (11.7%). 5 patients had a double infection.
      There were no distinctive clinical and radiological features found to be
      diagnostic for any etiologic agent. Hospital stay averaged 12.1 days. 35% of the
      patients included in the study were been treated by beta-lactam, often
      parenterally, nevertheless 88 pathogens of the 100 identified were resistant to
      this antimicrobial therapy. We believe that there should always be a macrolide,
      erythromycin or the latest ones such as azythromycin, in the treatment of CAP,
      owing to their efficiency, ease of use and lower cost.

PMID- 7501226
TI  - [The vascular changes in arterial hypertension].
AB  - Although the causes of high blood pressure vary, it is becoming clear that
      sustained hypertension is associated with changes in cardiovascular structure:
      left ventricular hypertrophy, decrease in big-medium arteries compliance and
      increased wall thickness of small arteries. To some extent, these alterations are
      natural physiological responses and are protective. However, the risk of
      circulatory death is closely related to left ventricular hypertrophy, and
      therefore, it is suggested increasingly that effective antihypertensive treatment
      requires normalization not only of blood pressure but also of vascular structure.
      The purpose of this brief review is to identify the type of functional and
      structural changes that are found in arteries of hypertensive individuals.

PMID- 7501227
TI  - [Evoked potentials and headache].
AB  - The multiform clinical varieties of idiopathic headache still represent an
      unclearly defined nosological entity; what is more, there is still no definitive
      etiopathogenetic and clinical classification which is unanimously supported by
      specialists in this sector. Moreover, given that the physiopathological mechanism
      which triggers off the various forms of headache is still not completely clear,
      yet it is obvious that research is focused on the identification of a test which
      is valid in terms of clinical diagnosis but at the same time can contribute
      towards neurophysiological examination. In order for a test to be of practical
      use also in terms of neurophysiological research, as well as being diagnostic, it
      should be able to examine the patient's neurosensory function, offering
      advantages in clinical terms, and contribute to clarifying the role of
      neurotransmitters in pain genesis. The test must also be non-invasive, offer
      comparable results, be repeatable after short intervals and be well tolerated by
      children. These represent the fundamental characteristics of a test which is
      applicable to the heterogeneous population of headache sufferers. In this context
      evoked potentials (EPs), using various forms of sensorial stimulus, appear to
      represent the ideal test; by exploring the well known and anatomically well
      defined neuronal systems at various levels of the CNS, they also help to explore
      the neurotransmitter function of the former, providing further information
      regarding the genesis of the crisis. A review of the literature examined in the
      present study showed the validity of the tests both in discriminating the various
      clinical forms of headache and supplying important information regarding the
      neurotransmitter-related genesis of the chain of nervous and vascular alterations
      leading to cephalic pain.

PMID- 7501228
TI  - [Ischemic hepatitis: case reports and a review of the literature].
AB  - Ischemic hepatitis represents a condition in which an acute circulatory failure
      determines a striking elevation of both serum transaminases and total bilirubin
      and a prolongation of prothrombin time. Such impairment of liver function tests
      is due to a haemodynamic hepatocyte injury, showing focal centrilobular necrosis
      as the specific pathologic correlate. In this paper the authors describe four
      different cases of ischemic hepatitis, in which an acute derangement of liver
      function tests occurred as a consequence either of myocardial failure or of
      systemic venous congestion. Finally, the authors review all current international
      literature concerning the various clinical, pathologic and therapeutic features
      of ischemic hepatitis.

PMID- 7501229
TI  - [Acute hepatotoxicity from amiodarone].
AB  - The functional and histological liver alterations induced by amiodarone treatment
      have been well known for some time and often consist in isolated increases in
      transaminase levels during long-term treatment. Secondary phospholipidosis was
      observed in these cases, an alteration which suggests the presence of toxic
      damage. Reports in the literature also indicate acute liver intoxication,
      including a number of fatal cases. This paper reports the finding of acute
      alterations of laboratory parameters indicative of hepatocytonecrosis with
      alterations of protein synthesis capacity following the first dose of the drug
      and which regressed after its suspension. On the basis of a review of the
      literature the authors propose that, in addition to a dose-dependent toxic
      mechanism, immunogenic or idiosyncratic mechanisms may also play a role in the
      onset and manifestation of acute liver intoxication by amiodarone.

PMID- 7501230
TI  - [Pseudothrombophlebitis due to an expansive popliteal cyst associated with
      Reiter's syndrome].
AB  - Popliteal cysts presenting as thrombophlebitis are unusual diseases of the
      popliteal fossa and are commonly associated with rheumatoid arthritis or meniscal
      tears. The authors report the case of a 38-year-old man with Reiter's syndrome in
      which a synovial cyst of the popliteal space, mimicking symptoms suggestive of
      deep venous thrombosis, complicated the course of the arthritis. Clinical and
      diagnostic features of this rare popliteal pathology are discussed and the
      usefulness of noninvasive diagnostic methods for detecting this disease, in
      particular that of echotomography, is emphasized. The authors stress the
      importance of a correct diagnosis in order to avoid the risks of an erroneous
      anticoagulant treatment.

PMID- 7501231
TI  - Neurotoxic injury in rat hippocampus differentially affects multiple trkB and
      trkC transcripts.
AB  - In the present work we determined, by Northern blotting, ribonuclease assay and
      in situ hybridization, the level of multiple trkB and trkC transcripts at
      different times after ibotenic acid-induced neuronal injury in the rat
      hippocampus. All the transcripts (7.0-7.5, 2.4 and 1.8 kb) encoding the truncated
      TrkB receptor are coordinately up-regulated following neurotoxic injury, with a
      time-course similar to that observed for the glial fibrillary acidic protein
      mRNA, a molecular marker of reactive astrocytes. The highest level of induction
      was observed for the 2.4 kb mRNA level. The 1.8 kb mRNA, whose relative level is
      higher in astroglial cultures compared to normal brain tissue, is detectable only
      in the gliotic hippocampus. The 9 kb trkB mRNA, which encodes the full-length
      TrkB receptor, rapidly decreases with a time-course similar to that previously
      observed for other neuronal markers. In situ hybridization studies show that the
      increased mRNA level per cell is a major determinant in the up-regulation of
      truncated trkB expression. A decrease of truncated and full-length trkC mRNA was
      observed in the neuron-depleted astroglia-enriched hippocampus, suggesting that
      this mRNA is mainly localized in the neuronal layers and that no induction of its
      expression occurs in reactive astrocytes.

PMID- 7501232
TI  - Nicotine increases intracellular calcium in rat hippocampal neurons via voltage
      gated calcium channels.
AB  - The effect of nicotinic receptor activation on intracellular calcium
      concentrations ([Ca2+]i) was quantitated in populations of cultured hippocampal
      neurons loaded with Fura-2. Nicotine (50 microM) and cytisine (50 microM)
      increased [Ca2+]i by 100%. This response was abolished in the presence of the
      nicotinic antagonist methyllycaconitine (MLA) whereas KCl-evoked increases in
      [Ca2+]i were insensitive to MLA. Glial cultures were unaffected by nicotine,
      although they did respond to glutamate with increased [Ca2+]i. In hippocampal
      neurons, responses to nicotinic agonists and KCl were dependent on the presence
      of extracellular Ca2+ and were similarly sensitive (85% inhibition) to CdCl2.
      These results are consistent with the presence of functional nicotinic receptors
      on hippocampal neurons. The receptors appear to elevate [Ca2+]i by promoting the
      influx of extracellular Ca2+ through voltage-gated calcium channels.

PMID- 7501233
TI  - The extent of amyloid deposition in brain in patients with Down's syndrome does
      not depend upon the apolipoprotein E genotype.
AB  - The extent of deposition of amyloid beta protein (A beta) was investigated in 20
      elderly patients with Down's syndrome, using the end-specific monoclonal
      antibodies BC05 and BA27 to detect the presence of A beta 42(43) and A beta 40
      (respectively), and related to apolipoprotein E (ApoE) genotype. No significant
      differences in the amount of A beta deposited in the brain, either as A beta
      42(43) or A beta 40, were noted in patients possessing an ApoE E4 allele,
      compared to those without. Patients with an ApoE E4 allele in general died at an
      earlier age than those with only ApoE E3 alleles, the latter in turn being
      outlived by those with an ApoE E2 allele. In Down's syndrome therefore, ApoE may
      influence the timing of onset, or the rate of progression, of disease but without
      affecting the type or total amount of pathology accumulated.

PMID- 7501234
TI  - Activation of the thyrotropin-releasing hormone (TRH) receptor by a direct
      precursor of TRH, TRH-Gly.
AB  - We studied the mechanism by which thyrotropin-releasing hormone (TRH)-Gly
      stimulated prolactin and thyrotropin (TSH) secretion in pituitary, using a
      pituitary mammotropic cell line, GH3 cells, and a cell line stably expressing a
      human TRH receptor (TRH-R). In GH3 cells expressing endogenous TRH-R, an addition
      of TRH-Gly evoked an immediate rise of intracellular calcium concentration,
      indicating that TRH-Gly reacted directly without converting from TRH-Gly to TRH.
      In order to determine whether this reaction might occur through TRH-R, we
      established a cell line stably expressing a human TRH-R, by transfecting a human
      TRH-R cDNA into Chinese hamster ovary cells (CHO cells). In this cell line, 10 nM
      TRH elevated intracellular calcium significantly; the Kd for MeTRH was 1.7 nM.
      One micromolar and 100 nM TRH-Gly also elevated intracellular concentration of
      calcium significantly, but not in CHO cells which were not transfected with the
      TRH-R cDNA. Competition studies further revealed that TRH-Gly displaced MeTRH
      binding (IC50, 12 microM). These data indicate that at high concentration, TRH
      Gly interacts directly with TRH-R to activate signal transduction pathway, and
      that release of prolactin and TSH induced by TRH-Gly in vitro may be due, at
      least in part, to the direct effect of TRH-Gly on the TRH-R.

PMID- 7501235
TI  - Distribution of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent
      diaphorase staining in intraparenchymal blood vessels of the rat brain.
AB  - The distribution of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent
      diaphorase (nitric oxide synthase, NOS) in the endothelial lining of
      intraparenchymal blood vessels was examined in sections of rat brain prepared
      from 500 microns thick slices of brain fixed by immersion or from blocks of
      tissue taken from whole brains fixed by vascular perfusion. In immersion-fixed
      tissue, a network of stained vessels, many as small as 3 microns in diameter was
      seen throughout the grey and white matter. In tissue fixed by perfusion small
      calibre vessels less than 5 microns were less prevalent. The results indicate
      that NOS is normally present in the endothelial lining throughout the
      cerebrovascular tree, including the capillaries. Endothelium-derived nitric oxide
      could have a more widespread role in the regulation of cerebral blood flow than
      considered previously.

PMID- 7501236
TI  - Subcutaneous carrageenan, but not formalin, increases the excitability of the
      nociceptive flexor reflex in the rat.
AB  - The effects of subcutaneous (s.c.) administration of formalin or carrageenan to
      the rat hindpaw on the ipsilateral nociceptive flexor reflex was examined in
      decerebrate, spinalized, unanesthetized rats in order to assess the development
      of spinal hyperexcitability following peripheral inflammation. Carrageenan
      induced a weak and brief EMG discharge at the time of injection, followed by a
      gradual and delayed increase in flexor reflex magnitude, becoming significant 120
      min postinjection. In addition, carrageenan induced a decrease in response
      threshold to peripheral mechanical stimulation as early as 30 min postinjection.
      Formalin induced an immediate and intense motor discharge which usually decreased
      after 5-10 min and was followed by a second phase of relatively weak motor
      discharge lasting for 20-70 min. However, the effect of s.c. formalin on the
      excitability of the flexor reflex was variable with either facilitation or
      inhibition. The flexor reflex was significantly depressed after formalin from 90
      min post-injection. It is suggested that carrageenan induced prolonged spinal
      sensitization to nociceptive input, possibly through the induction of peripheral
      inflammation. In contrast, although formalin generated afferent input and evoked
      motor discharges, it did not induce significant spinal hyperexcitability. Thus,
      carrageenan, but not formalin, is useful to study central sensitization following
      peripheral chemical stimulation and/or inflammation.

PMID- 7501237
TI  - Effect of raised Mg2+ on the antidromic activation of immature rat spinal
      motoneurones in vitro.
AB  - Currents elicited by electrical stimulation of the ventral root were recorded
      from motoneurones of the immature rat spinal cord in vitro using the patch
      pipette technique. Control medium contained Ca2+ (1.5 mM) and Mg2+ (0.75 mM). In
      nine preparations the mean amplitude of antidromic current responses was 5.12 +/-
      0.41 nA. Raising Mg2+ (EC50 9.6 +/- 1.1 mM) to levels up to 50 mM produced an all
      or-none maximal depression of the current responses by 69 +/- 1%. These levels of
      Mg2+ depressed currents elicited by depolarizing command steps by only 30% and
      compound action potentials recorded in ventral roots by only 17%. It is concluded
      that raised Mg2+ caused conduction block from the initial segment to the soma
      dendritic region of motoneurones. This non-synaptic depressant action of raised
      Mg2+ should be considered when raised Mg2+ is used in order to specifically block
      synaptic activity in vitro.

PMID- 7501238
TI  - Econazole, a blocker of Ca2+ influx, selectively suppresses LTP of EPSPs in
      hippocampal slices.
AB  - Econazole--an agent that suppresses Ca2+ influx triggered by depletion of
      internal Ca-stores in non-excitable cells--was bath-applied to submerged slices
      from Sprague-Dawley rats. Econazole (15-20 microM) had no consistent effect on
      afferent volleys, EPSPs or population spikes; but in seven out of nine slices, it
      prevented the induction of tetanic long-term potentiation (LTP) of field EPSPS.
      By contrast, all slices showed a marked LTP of population spikes. Ca2+ influx
      induced by tetanic depletion of Ca2+ stores may be essential for LTP of
      excitatory synaptic transmission.

PMID- 7501239
TI  - Chronic treatment with thioctic acid does not protect against malonate toxicity
      in vivo.
AB  - We reported previously that short-term systemic pretreatment with thioctic acid
      is protective against NMDA and malonate lesions of the striatum. In the current
      study, we examined the effects of 3 weeks of pretreatment with various doses of
      thioctic acid (5-60 mg/kg per day) on malonate-induced striatal degeneration in
      adult rats. In this paradigm, we were unable to demonstrate protection against
      malonate toxicity. The reasons for the difference in efficacy between subacute
      and chronic treatment remain to be defined.

PMID- 7501240
TI  - Increase in the septal vasopressin content by prolyl endopeptidase inhibitors in
      rats.
AB  - Prolyl endopeptidase (PEP; EC 3.4.21.26) cleaves the Pro-Arg bond of arginine
      vasopressin (AVP). This study investigated the effects of PEP inhibitors, 1-[1
      (benzyloxycarbonyl)-L-prolyl]prolinal (Z-Pro-prolinal) and 1-[3-(2-indanylacetyl)
      L-thioprolyl]pyrrolidine (Z-321), on the AVP content in the septum of rats. Oral
      administration of Z-Pro-prolinal (100 mg/kg) and Z-321 (100 mg/kg) significantly
      increased the septal AVP content. At 10 mg/kg, Z-321 slightly increased the
      content. In contrast, the D-thioprolyl form of Z-321 (100 mg/kg), which lacks an
      inhibitory effect on the enzyme, failed to affect the AVP content. These results
      indicate that PEP inhibitors increase the content of AVP through inhibition of
      the enzyme activity in vivo. Therefore, it is suggested that PEP may contribute
      to the degradation of endogenous AVP in the brain.

PMID- 7501241
TI  - Immunohistochemical localization of neuronal nicotinic receptor subtypes at the
      pre- and postjunctional sites in mouse diaphragm muscle.
AB  - The existence of neuronal nicotinic acetylcholine receptor (nAChR) subunits was
      investigated in the cryostat sections of mouse diaphragm muscles using the
      indirect immunofluorescence technique. The specific immunolabelings with
      monoclonal antibodies (mAbs) to beta 2 and to alpha 8 subunits of neuronal nAChR
      were observed at the endplate determined by labeling with a fluorescent dye
      (BODIPY)-conjugated alpha-bungarotoxin. The immunoreactivity of mAb to the alpha
      3 subunit of neuronal nAChR was detected on the motor nerve fibers including the
      nerve terminals. These results provide evidence that the subtypes of postsynaptic
      nAChR, recognized by the anti-beta 2 and/or anti-alpha 8 mAbs, and the
      presynaptic nAChR recognized by the anti-alpha 3 mAb, are present at the
      neuromuscular junction, in addition to the classical muscle nAChR.

PMID- 7501242
TI  - The effect of PhTx3 on the release of 3H-acetylcholine induced by tityustoxin and
      potassium in brain cortical slices and myenteric plexus.
AB  - The venom of the Brazilian spider Phoneutria nigriventer possesses several
      neurotoxic polypeptidic fractions. Previous work has established that one of the
      toxic components, PhTx3, inhibited Ca(2+)-dependent glutamate release and the
      increase in cytosolic free Ca2+ in response to membrane depolarization. In the
      present work, we investigated the effect of PhTx3 on the release of acetylcholine
      (ACh) from brain and peripheral neurons. PhTx3 decreased the release of [3H]-ACh
      induced by tityustoxin and KCl in brain cortical slices and myenteric plexus. The
      inhibitory effect of myenteric plexus had the same magnitude as that obtained in
      the absence of extracellular Ca2+. However, in brain PhTx3 was less efficient at
      decreasing the evoked release of ACh. These experiments suggest that the target
      of PhTx3 is coupled to the process of release of ACh in brain and autonomic
      nervous system.

PMID- 7501243
TI  - A critical assessment of brain metabolites: analysis of perchloric acid extracts
      using proton nuclear magnetic resonance.
AB  - A critical assessment of perchloric acid (PCA) brain tissue extracts for precise
      identification and quantitation of brain metabolites using in vitro proton
      nuclear magnetic resonance (1H NMR) spectroscopy was studied. One pulse with a
      presaturation NMR experiment was used. The chemical shifts and coupling networks
      of the major brain metabolites as a function of pH were characterized by using
      individual model compounds and a model mixture solution. We found that the
      conditions of the PCA solution are essential for accurate interpretation of NMR
      spectra of brain metabolites. The maximum spectral resolution was obtained at pH
      4.92. Caution is necessary when using high resolution 1H NMR spectroscopy to
      identify and quantify brain metabolites.

PMID- 7501244
TI  - Effect of minute amounts of [D-Ala2,MePhe4,Gly(ol)5]enkephalin injected into the
      tuberomammillary nucleus of rats on histamine release from the cerebral cortex.
AB  - [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAGO) (10 ng/0.5 microliters saline solution)
      injected into the tuberomammillary nucleus (TM) of rats in minute amounts
      decreased the amount of histamine released to approximately 50% of the basal
      value on measurements taken 20-40 min after administration. This effect of DAGO
      was inhibited by the simultaneous microinjection of naloxone (320 ng). These
      results may be explained in two ways. The first is that the stimulation of mu
      receptors results in the inhibition of histaminergic cell bodies. The second is
      that the somatodendritic release of histamine was increased by the stimulation of
      mu-receptors and as a result of increased histamine concentration in TM, many
      histaminergic neurons may be inhibited through the stimulation of H3-receptors.
      Further studies are necessary regarding the influence of mu-agonists on various
      cellular sites of histaminergic neurons.

PMID- 7501245
TI  - Ex vivo demonstration of nitric oxide in the rat brain: effects of intrastriatal
      endothelin-1 injection.
AB  - Nitric oxide (NO) is a novel transmitter with multiple functions in endothelium
      and neuronal tissue. In particular, it has been implicated in the pathogenesis of
      neurodegenerative diseases. The aim of the present study was to demonstrate the
      ex vivo detection of NO in basal conditions and after ET-1 intrastriatal
      injection by means of electron paramagnetic resonance (EPR) spectroscopy using
      locally injected hemoglobin (Hb) as a NO trapping agent. The extent of
      neostriatal damage after Hb and ET-1 injections was assessed by means of
      immunocytochemistry with a monoclonal antibody against dopamine and cAMP
      phosphoprotein M(r) 32 (DARPP-32), which is considered a marker of striatal
      intrinsic neurons. In the absence of local Hb injection, no signal related to
      endogenous NO was detected in the neostriatum, suggesting that endogenous NO
      trapping agents are not sufficiently concentrated to allow NO detection with the
      present technique. Instead, 1 h after Hb injection, a clear nitrosyl-Hb signal
      can be detected in neostriatal homogenates. ET-1, a powerful vasoconstrictor
      agent, was used to cause neuronal loss in the neostriatum. No change in nitrosyl
      Hb signal was observed in neostriatal 1 h after ET-1 injection, whereas an almost
      3-fold increase in the signal intensity was present 24 h after ET-1 injection.
      The analysis of neostriatal damage showed that Hb injection did not cause either
      significant damage of striatal tissue or potentiation of ET-1-induced lesions. In
      conclusion, the present technique allows ex vivo detection of NO in the brain.
      The delayed increase in NO observed after ET-1 injection indicates that this
      molecule may participate in the development of slowly progressive neuronal damage
      occurring at late post-ischemic times.

PMID- 7501246
TI  - Metabotropic glutamate receptor agonists reduce paired-pulse depression in the
      dentate gyrus of the rat in vitro.
AB  - We have analyzed the effects of agonists acting at different classes of
      metabotropic glutamate receptors (mGluRs) on paired pulse depression (PPD) at the
      medial perforant path/granule cell synapse. Drugs were bath applied and paired
      pulses delivered at 3-min intervals during control and during drug application.
      Both 1S,3R-1-aminocyclopentane- 1,3-dicarboxylic acid (1S,3R-ACPD, 100 microM),
      which acts at class I (mGluR1, 5) and class II (mGluR2, 3) mGluRs and L-2-amino-4
      phosphobutyric acid (L-AP4, 100 microM) which is specific for class III (mGluR4,
      6-8) mGluRs, strongly reduced PPD with an interstimulus interval (ISI) of 40 ms
      (P < 0.001). The class I specific agonists trans-azetidine-2,4,dicarboxylic acid
      (t-ADA, 100 microM) and 3,5,dihydroxyphenylglycine (DHPG, 100 microM) did not
      affect PPD. The relatively specific class II agonists S-3-carboxy-4
      hydroxyphenylglycine (3C4HPG) and 2S,3S,4S-alpha- carboxycyclopropyl-glycine (L
      CCG-I) did reduce PPD, but only at very high concentrations (500 and 40 microM
      respectively) with respect to their EC50 values. These results suggest that two
      types of mGluRs control PPD at this synapse--a class III mGluR and a class II
      like mGluR, which may not correspond to one of the currently cloned receptors.

PMID- 7501247
TI  - Desynchronization and recovery of beta rhythms during brisk and slow self-paced
      finger movements in man.
AB  - Event-related desynchronization (ERD) and recovery of EEG beta rhythms (15-26 Hz)
      were studied during slow and brisk self-paced index finger extension and flexion.
      beta rhythms started to recover earlier in brisk movements. Brisk movements
      showed no correlation between duration of EMG burst in the extensor muscle and
      the latency of recovery whereas slow movements did. In contrast to beta-ERD which
      was widespread, the recovery and rebound of beta rhythms occurred in a
      circumscribed focus close to the hand MI area.

PMID- 7501248
TI  - Estrogen receptor-like immunoreactivity in the medullary and spinal dorsal horn
      of the female rat.
AB  - Using an immunohistochemical technique, we demonstrate that large numbers of
      neurons in the laminar spinal trigeminal nucleus and spinal gray matter of the
      female rat express estrogen receptors (ER). Densely packed ER-immunoreactive
      neurons were present in lamina II, but labeled neurons were also present in
      lamina I, the neck of the dorsal horn, and in lamina X. Labeling was present
      throughout the length of the spinal cord, with the exception of segments caudal
      to S1, which were unlabeled. The distribution of ER-containing neurons to areas
      that are involved in processing of primary afferent nociceptive information
      suggests that the pain modulatory effects of estrogen may be exerted at the
      spinal level.

PMID- 7501249
TI  - Can the alpha 2-adrenoceptor agonist-mediated suppression of nocifensive reflex
      responses be due to action on motoneurons or peripheral nociceptors?
AB  - To exclude the possibility that the suppression of nocifensive reflex responses
      induced by alpha 2-adrenergic agents is due to action on alpha-motoneurons or
      peripheral nociceptors, we studied the effect of medetomidine, an alpha 2
      adrenoceptor agonist, on the monosynaptic reflex and on the primary afferent
      nociceptor-mediated antidromic vasodilator response in rats. Additionally, the
      effect on the dorsal root potential, an index of a transient excitability change
      in the central terminals of primary afferent fibers, was determined. Medetomidine
      was applied systemically at doses (100 and 300 micrograms/kg) which have proven
      strongly antinociceptive in previous studies. The amplitudes of a submaximal
      monosynaptic reflex volley or a submaximal dorsal root potential were not changed
      by medetomidine. Medetomidine induced a decrease of cutaneous blood flow but did
      not abolish the vasodilatatory response to antidromic stimulation of the sciatic
      nerve at C-fiber intensity as determined by the laser Doppler flow method. The
      results indicate that the alpha 2-adrenoceptor-mediated suppression of
      nocifensive reflex responses is not caused by a decreased excitability of
      motoneurons or peripheral nociceptors. An alpha 2-adrenoceptor agonist does not
      modulate the transient stimulus-evoked change in the excitability of central
      terminals of primary afferent fibers.

PMID- 7501250
TI  - Diversity in localisation of nitric oxide synthase antigen and NADPH-diaphorase
      histochemical staining in sacral somatic motor neurones of the cat.
AB  - Nitric oxide synthase (NOS) immunoreactivity occurred in about 60% of
      ventromedial, ventrolateral, and sphincteric motoneurones in cat sacral spinal
      cord. Proportions of sacral motoneurones histochemically stained for NADPH
      diaphorase, were similar, and equivalent in size to those immunoreactive for NOS,
      suggesting co-localisation of diaphorase and NOS. Double staining techniques
      revealed that NOS co-localised with NADPH-diaphorase in approximately 60% of
      sacral motoneurones. Some remaining motoneurones exhibited neither NOS nor NADPH
      diaphorase, while others exhibited only NOS or NADPH-diaphorase, indicating
      phenotypic differences among sacral motoneurones.

PMID- 7501251
TI  - Botulinum toxin type A inhibits Ca(2+)-dependent transport of acetylcholine in
      reconstituted giant liposomes made from presynaptic membranes from cholinergic
      nerve terminals.
AB  - Giant liposomes were made from a mixture of asolectin phospholipid vesicles and
      presynaptic plasma membranes isolated from Torpedo cholinergic nerve endings.
      Acetylcholine filled giant liposomes were able to release neurotransmitter upon
      stimulation by the Ca2+ ionophore A23187 and Ca2+. Botulinum neurotoxin type A
      inhibited this Ca(2+)-dependent acetylcholine transport. Additionally, Botulinum
      toxin type A decreased membrane fluidity of liposomes. These results suggest that
      Botulinum toxin can interact directly with components of the presynaptic plasma
      membrane and inhibit acetylcholine translocation. Furthermore, since the
      reconstituted liposomes do not have synaptic vesicle components, the observed
      effects may account for the action of Botulinum toxin on the non-quantal release
      of acetylcholine from motor nerve terminals.

PMID- 7501252
TI  - Adenosine A2A receptors stimulate acetylcholine release from nerve terminals of
      the rat hippocampus.
AB  - The nature of the adenosine receptors involved in the enhancement of
      acetylcholine release in the hippocampus was studied. The A2A agonist, CGS 21680,
      increased the veratridine-evoked release of [3H]acetylcholine from hippocampal
      synaptosomes. This presynaptic effect of CGS 21680 was greater at 3-30 nM than at
      100 nM. The excitatory effect of CGS 21680 was antagonised by the A2 antagonist,
      DMPX (10 microM), and by the A2A antagonist, CSC (200 nM), but not by the A1
      antagonist, DPCPX (20 nM). We also found co-expression of A2A and choline
      acetyltransferase mRNAs in the nucleus of the diagonal band and the medial
      septum, where the cholinergic cell bodies that project into the hippocampus are
      located. These results indicate that A2A adenosine receptors are present in
      cholinergic nerve terminals in the hippocampus and that activation of these
      receptors enhances acetylcholine release.

PMID- 7501253
TI  - Pharmacological characteristics of potassium-induced, glycogenolysis in
      astrocytes.
AB  - Elevated extracellular concentrations of the potassium ion ([K+]o) stimulate
      glycogenolysis in primary cultures of mouse astrocytes that have been grown in
      the presence of dibutyryl cyclic AMP but not in corresponding cultures which have
      not been treated in this manner. The response is potently inhibited by
      nifedipine, suggesting that it is evoked by entry of calcium ions through voltage
      dependent L-channels. The benzodiazepine midazolam, which is known to enhance
      calcium entry at concentrations of [K+]o causing submaximum calcium entry,
      increases the glycogenolytic effect by such levels of [K+]o.

PMID- 7501254
TI  - Effect of neurotoxin DSP4 on EEG power spectra in the rat acute model of
      epilepsy.
AB  - The effect of the adrenergic neurotoxin N-(chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP4) on electroencephalographic (EEG) activity was studied in
      the model of epilepsy induced by systemic application of penicillin (1,000,000
      IU/kg, i.p). DSP4 (50 mg/kg, i.p.) was administrated to male Wistar rats, while
      the control animals were rats from the same litters. EEG activity was recorded in
      acute and chronic experiments 3 or 4 weeks after DSP4 treatment, before and after
      penicillin administration. Occasional locus coeruleus (LC) stimulation served as
      an electrophysiological test of DSP4 toxic effect. EEG power spectra in DSP4
      treated animals showed a tendency to be greater in lower frequency bands than in
      controls before penicillin administration; there was almost no effect of
      electrical LC stimulation, regardless on penicillin treatment. In the model of
      epilepsy, the mean total EEG power spectra were greater in the period of 135-330
      min after penicillin administration, as well as during 345-540 min, in DSP4
      treated animals as compared to the controls. It seems that neurotoxin DSP4 is an
      optimal tool for studying the removal of LC influence in the acute model of
      epilepsy. It is also suggested that norepinephrine (NE) may have a modulatory
      role in the systemic penicillin epilepsy.

PMID- 7501255
TI  - GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal
      fluctuation.
AB  - We previously reported four different mutations in the coding region of GTP
      cyclohydrolase I (GCH-I) gene in patients with hereditary progressive dystonia
      with marked diurnal fluctuation (HPD). We found two independent new mutations
      (leucine 79 proline and a deletion in exon 4) in patients with HPD. We also found
      four families of HPD without any mutations in the coding region of GCH-I gene.

PMID- 7501256
TI  - Recordings of glutamate-gated ion channels in outside-out patches from Drosophila
      larval muscle.
AB  - Outside-out patches of membrane were excised from muscle fibers 6 and 7 of third
      instar wild-type Drosophila larvae. Channels were observed to open in response to
      short pulses of L-glutamate. At a holding potential of -60 mV, the channels
      opened to one main conductance level of about 120 pS. The current-voltage plot
      for the channels was linear and reversed around 0 mV holding potential. The
      channels were also activated by quisqualate but not by aspartate, N-methyl-D
      aspartate (NMDA), kainate, glycine, gamma-aminobutyric acid (GABA) and
      acetylcholine. At high glutamate concentrations (3 or 10 mM), channel activation
      reached a peak within 0.3 ms. The channels opened in 'bursts' flickering between
      open and closed states. The channels opened only for a few milliseconds after
      switching on the glutamate and channel activity declined after the initial surge
      to zero with time constants between 5 and 20 ms. During applications of low
      glutamate concentrations (0.2-0.5 mM) to the same patch the channels opened much
      less frequently and during most applications no openings were observed. The
      openings observed were short and 'bursts' of openings were rare. Two exponential
      components were identified in the open-time distribution obtained with pulsed
      applications of glutamate (0.5-10 mM) with time constants of about 0.1 and 2.0
      ms. The kinetics of the channels seem to be similar to the kinetics of certain
      glutamate gated channels found on muscle of crayfish and locust.

PMID- 7501257
TI  - Prostaglandin E2 stimulates glutamate release from synaptosomes of rat spinal
      cord.
AB  - We recently reported that intrathecal administration of prostaglandin E2 induced
      hyperalgesic and allodynic effects through the glutamate receptor system. Here we
      examined whether prostaglandin E2 could evoke amino acid release from nerve
      terminals using rat spinal cord synaptosomes. Exposure in superfusion to
      prostaglandin E2 significantly increased endogenous glutamate and aspartate
      release and dose dependencies showed bell-shaped patterns with a peak at 1 nM.
      Both releases were almost absolutely Ca(2+)-dependent. These results demonstrate
      that prostaglandin E2 may stimulate the release of excitatory amino acids
      presynaptically in the spinal cord.

PMID- 7501258
TI  - The effect of continuous morphine analgesia on chronic thermal hyperalgesia due
      to sciatic constriction injury in rats.
AB  - We employed hindfoot withdrawal latencies to radiant heat to assess the analgesic
      effect of prolonged morphine infusion on thermal hyperalgesia induced by chronic
      constriction injury (CCI) of the rat sciatic nerve. All CCI rats developed
      thermal hyperalgesia while sham-operated animals did not. Continuous systemic
      infusion of morphine dose-dependently reversed the thermal hyperalgesia in the
      CCI rats. In contrast, thermal hyperalgesia persisted in saline-treated CCI rats.
      Tolerance to morphine's analgesic effect did not develop over a period of seven
      days of morphine infusion, which is considered long-term for animal models. These
      data suggest that morphine acts rapidly and effectively to reduce behavioral
      signs of hyperalgesia in rats with sciatic CCI, without the concomitant
      development of tolerance. Scheduled administration of morphine might be an
      appropriate treatment regimen for relief of neuropathic pain, and the infrequent
      use of opioids in equivalent human clinical pain syndromes due to fear of opioid
      unresponsiveness and tolerance might need to be re-evaluated.

PMID- 7501259
TI  - Lead inhibits Ca(2+)-stimulated nitric oxide synthase activity from rat
      cerebellum.
AB  - Pb2+ is reported to cause cognitive dysfunctions in children and to inhibit long
      term potentiation (LTP), a model form of synaptic plasticity that involves nitric
      oxide (NO). Since Pb2+ interacts with Ca(2+)-calmodulin, and brain nitric oxide
      synthase (NOS) is Ca(2+)-calmodulin regulated, we examined the effects of Pb2+ on
      NOS activity prepared from rat cerebellum. NOS required NADPH and was inhibited
      by monomethylarginine. Full NOS activity required 0.6 microM free Ca2+ and was
      inhibited 50% by 17 nM and 100% by 80 nM free Pb2+. NOS inhibition by Pb2+ was
      reversible by increasing free Ca2+ concentrations. Evaluation of other divalent
      cations resulted in the following ranked order of potencies: Cu2+ > Pb2+ >> Zn2+;
      Fe2+, Ba2+, Mg2+, Mn2+, and Sr2+ were ineffective. These results suggest that
      Pb2+ inhibition of brain NOS activity may account for some of the effects of Pb2+
      on the CNS.

PMID- 7501260
TI  - Does barbiturate anesthesia modify the neuronal properties of the somatosensory
      thalamus? A single-unit study related to nociception in the awake-pentobarbital
      treated rat.
AB  - By means of extracellular recordings, we studied thalamic ventrobasal complex
      neurons of rats tested first awake, and then anesthetized with pentobarbital. In
      both conditions, we found two groups of units in both states. The first group,
      displaying a spontaneous bursting activity, was not obviously responding to
      peripheral stimuli. Another group, displaying a single-spike activity, was almost
      exclusively activated by innocuous and/or noxious and innocuous mechanical
      stimuli. Still in this group, units specifically driven by noxious stimuli were
      only found under pentobarbital. These data, different from classical findings,
      emphasize the interest of the awake preparation in order to study nociceptive
      cellular mechanisms at the thalamic level.

PMID- 7501261
TI  - Electrophysiological characterization of nicotinic receptors of aneurally grown
      human myotubes.
AB  - It seems necessary to characterize electrophysiological properties of human
      nicotinic acetylcholine receptors (nAChR) to obtain reference values for the
      study of diseased muscles. We therefore investigated nAChRs in aneurally grown
      human myotubes using the patch-clamp technique. Pulses of acetylcholine (ACh)
      were applied to outside-out patches with a fast application system. The peak and
      the rise time of the current elicited by pulses of various concentrations of ACh
      were evaluated. The results were interpreted using the circular reaction scheme
      developed recently for the nAChR of embryonic mouse muscle. In addition, the
      burst duration and the slope conductance of the ACh activated channel were
      evaluated.

PMID- 7501262
TI  - Evidence of decreased GABAergic influence on temporal integration in the inferior
      colliculus following acute noise exposure: a study of evoked potentials in the
      rat.
AB  - Many investigations have shown that modulation of sensory input, either by over
      stimulation or sensory deprivation, can cause a reorganization of structures
      located high in the central nervous system (CNS). Although most of these studies
      had focused on studying changes in the function and tonotopic organization of the
      sensory cortex, recent evidence has suggested that plastic changes in specific
      subcortical nuclei of sensory systems may also occur in response to modulation of
      sensory input, and may be partially responsible for changes reflected at the
      level of the cortex. In the present study we investigated the effects of noise
      exposure (4-kHz continuous tone at 104 dB sound pressure level (SPL) for 30 min
      duration) on the processing of auditory information at the level of the inferior
      colliculus (IC). We studied how evoked potentials recorded from the surface of
      the IC changed as a function of the duration of the tone bursts used as stimuli.
      We measured the amplitude of a peak that is generated postsynaptically in the IC
      in response to tone bursts between 1 and 6 ms duration. In animals that were not
      exposed to the tone, the amplitude of this peak decreased with increasing
      stimulus duration, but after tone exposure, the decrease in the amplitude of this
      peak was significantly less than in the animals not exposed to the tone. A
      microinjection of the GABAA antagonist, bicucullene, into the IC in the animals
      not exposed to the tone caused the amplitude of the peak to be less dependent on
      tone burst duration, which indicates that the decrease in the amplitude of this
      component of the response from the IC with increasing stimulus duration is a
      result of GABAA mediated inhibition on IC neurons. The tone exposure caused a
      similar decrease in amplitude of this component of the response from the IC, thus
      indicating that noise exposure reduced the GABAA mediated component of this
      function. This is supported by the finding that microinjections of bicucullene
      into the IC of noise-exposed animals did not significantly change the
      relationship between the amplitude of this peak and the stimulus duration.

PMID- 7501263
TI  - In vivo pharmacological study of spermine-induced neurotoxicity.
AB  - Spermine-induced neurotoxicity and its pharmacological manipulation was studied
      in the rat striatum in vivo. Spermine (50, 100, 250 nmol) was injected into the
      striatum and the volume of damage quantified by computer-based image analysis.
      Spermine produced a dose-dependent increase in the volume of damage. Co
      administration of MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten
      5,10-imine maleate; dizocilpine, 60 nmol), 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo[f]quinoxaline (25, 40 nmol) and pretreatment with pentobarbital (40 mg/kg,
      i.p.) significantly reduced the volume of damage induced by 100 nmol spermine. MK
      801 (30 nmol) was also effective in reducing the damage induced by 50 nmol
      spermine. Treatment with a specific inhibitor of nitric oxide synthase, N omega
      nitro-L-arginine methyl ester (50 mg/kg, i.p., twice daily for 10 days) was
      ineffective. These results suggest an involvement of both N-methyl-D-aspartate
      (NMDA) and non-NMDA glutamate receptors in the cascade of spermine-induced
      neurotoxicity.

PMID- 7501264
TI  - The suppression of age-related accumulation of lipid peroxides in rat brain by
      administration of Rooibos tea (Aspalathus linearis).
AB  - The protective effects of Rooibos tea (RT), Aspalathus linearis, against damage
      to the central nervous system (CNS) accompanying aging were examined by both the
      thiobarbituric acid reaction (TBA) and magnetic resonance imaging (MRI) methods
      in brains of chronically RT-treated rats. Ad libitum administration of RT was
      begun with 3-month-old Wistar female rats and continued for 21 months. The
      contents of TBA reactive substances (TBARS) in the frontal cortex, occipital
      cortex, hippocampus and cerebellum in 24-month-old rats after administration with
      water were significantly higher than those in young rats (5 weeks old). However,
      no significant increase of TBARS was observed in RT-administered aged rats. When
      MR images of the brains of 24-month-old rats with and without RT as well as 5
      week-old rats were taken, a decrease of the signal intensity was observed in the
      cerebral cortex, hippocampus and cerebellum in MR images of aged rats without RT,
      whereas little change of the signal intensity was observed in MR images of the
      same regions of 24-month-old rats treated with RT, whose images were similar to
      those of young rats. These observations suggested that (1) the age-related
      accumulation of lipid peroxides in the brain was closely related to the
      morphological changes observed by MRI, and (2) chronic RT-administration
      prevented age-related accumulation of lipid peroxides in several regions of rat
      brain.

PMID- 7501265
TI  - Heat-shock cognate 70 messenger RNA expression in postmortem human hippocampus:
      regional differences and age-related changes.
AB  - In situ hybridization of postmortem human brain tissue showed that constitutive
      heat-shock cognate 70 (hsc 70) mRNA was expressed in more than 50% of the
      pyramidal neurons in the hippocampal subfields. The ratio (%) of the hsc 70 mRNA
      expressing neurons to the total neurons was significantly greater in CA3 and the
      hilus than in CA1 and CA2. The lower ratio in CA1 may be related to its
      vulnerability to various stresses. The ratio of hsc 70 mRNA-expressing neurons in
      CA1 was significantly greater in the older subjects than in the younger ones.
      This may reflect the up-regulated hsc 70 mRNA induction in response to a
      reduction in free hsc 70 because the binding of hsc 70 to aberrant proteins may
      be increased in aged persons.

PMID- 7501266
TI  - Na+ dependent Ca2+ influx induced by depolarization in neurons dissociated from
      rat nucleus basalis.
AB  - Neurons were acutely dissociated from the rat nucleus basalis, and whole-cell
      patch clamp recordings were made. Voltage dependent calcium currents (ICa) were
      recorded and fura-2 microfluorimetric recordings of intracellular free Ca2+
      concentration ([Ca2+]i) were made at the same time. In Na(+)-containing solution,
      a depolarization from -60 to +40 mV evoked the maximal increase in [Ca2+]i, and
      this decreased to 43% of the maximal with a large depolarization to +120 mV. The
      [Ca2+]i increase induced by the large depolarization (+20 to +120 mV) was
      inhibited by perfusion of Na(+)-free external solution, and was less when the
      recording pipette contained a peptide (PRLLFYKYVYKRYRAGKQRG, named XIP) known to
      inhibit Na/Ca exchange. These results suggest that the [Ca2+]i increase by the
      large depolarization is mediated by reverse operation of Na/Ca exchange (Ca2+
      inward and Na+ outward).

PMID- 7501267
TI  - 1-Methyl-4-phenyl-pyridinium (MPP+) uptake does not explain the differential
      toxicity of MPP+ in the nigrostriatal and mesolimbic dopaminergic pathways.
AB  - The present study examined the possible differential toxicity of 1-methyl-4
      phenyl-pyridinium (MPP+) in the nigrostriatal and mesolimbic dopaminergic
      pathways in BALB/c mice, and investigated whether MPP+ uptake may account for
      this differential toxicity. Results indicated that chronic MPP+ infusions to the
      striatum (ST) and nucleus accumbens (NAc) both produced a toxicity on dopamine
      (DA) neurons. However, MPP+ produced a more severe DA depletion in the ST than in
      the NAc. Kinetic analyses from MPP+ uptake studies revealed a similar Km value in
      both the ST and NAc, suggesting that the affinity for MPP+ uptake is not
      different. The Vmax was approximately 1.6-fold higher in the ST than in the NAc.
      These results together suggest that chronic MPP+ infusions produce a differential
      toxicity on DA neurons in the nigrostriatal and mesolimbic dopaminergic pathways
      and that the ability of MPP+ uptake in DA terminals probably does not account for
      this differential toxicity.

PMID- 7501269
TI  - Cytochemical localization of adenylyl cyclase activity within the sensory
      epithelium of the trout saccule.
AB  - Adenylyl cyclase, the enzyme of synthesis of cAMP, the second messenger molecule
      mediating signal transduction in response to sensory, neurotransmitter and
      hormonal stimuli, has been localized in the sensory epithelium of the rainbow
      trout (Salmo gairdneri R.) saccule by cytochemical detection of enzyme activity.
      In the sensory receptor cell, or hair cell, reaction product has been visualized
      in the stereocilia in close association with the outer cell membrane and also at
      the apical surface of the cuticular plate. A diffuse distribution of precipitate
      was observed within the cytoplasm of terminal endings of nerve fibers presumed to
      be efferent on the basis of characteristic synaptic specializations including
      presynaptic vesicles and a postsynaptic cistern lying within the hair cell.
      Occasionally, reaction product was observed to be associated with the external
      cell membrane of these nerve terminals. There appeared to be little or no
      adenylyl cyclase activity associated with the plasma membrane at the base of the
      hair cell or in presumptive afferent nerve endings. However, a subpopulation of
      nerve fiber endings which exhibited both efferent and afferent synaptic
      specializations contained precipitate. A concentration of adenylyl cyclase
      activity in hair cell stereocilia and efferent nerve terminals in the sensory
      epithelium is suggestive of a role for cAMP in second messenger action at these
      sites, possibly related to mechanosensory transduction and efferent
      neuromodulation, respectively.

PMID- 7501268
TI  - Rat brain binding sites for pramipexole, a clinically useful D3-preferring
      dopamine agonist.
AB  - Pramipexole (PPX) is currently being evaluated for treatment of schizophrenia and
      Parkinson's disease. In studies with cloned subtypes of the dopamine (DA) D2
      receptor subfamily, PPX has higher affinity for the D3 compared to the D2 and D4
      subtypes; unlike 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), it
      does not bind to sigma sites. Receptor binding autoradiography with [3H]PPX (5
      nM, 62 Ci/mmol) was used to evaluate the distribution of PPX binding sites within
      the rat brain. Consistent with its preference for D3-binding sites, the highest
      concentrations of [3H]PPX binding sites were found in the islets of Calleja
      (ICj), previously reported to contain D3 but not D2 or D4 mRNA. [3H]PPX binding
      was also high in other mesolimbic areas such as the nucleus accumbens (N. accum),
      olfactory tubercle, and amygdala. [3H]PPX binding was also high in caudate (Cd),
      although slightly less than in mesolimbic areas. Less [3H]PPX binding sites were
      found in ventral tegmental area (VTA) and substantia nigra, areas rich in cell
      bodies for DA neurons. Thus, although PPX most potently stimulates DA
      autoreceptors, PPX binding sites have their highest concentrations in projection
      areas containing both DA terminal and postsynaptic receptors. Because of PPX's
      preferential affinity for the D3 receptor subtype and its resultant high
      mesolimbic binding, it could have a unique therapeutic profile for treatment of
      psychiatric and/or neurological diseases.

PMID- 7501270
TI  - Damped oscillatory activity in the guinea pig accessory olfactory bulb slice.
AB  - Extracellular field potentials were recorded from guinea pig accessory olfactory
      bulb (AOB) slices following electrical stimulation of the vomeronasal nerve layer
      (VNL). A single shock of the VNL provoked a characteristic damped oscillatory
      field potential, which consisted of a compound action potential followed by 6-7
      periodic negative peaks (n1, n2, n3, n4, n5, n6 or n7). The average frequency of
      the oscillation was 32 Hz. The existence of oscillation in the AOB suggests the
      possibility that the oscillatory activity not only may reflect 'quantal' sampling
      periods, but also may be dynamically altering the AOB conditions under which
      incoming pheromone-like information is processed.

PMID- 7501271
TI  - Expression of interleukin-11 and its encoding mRNA by glioblastoma cells.
AB  - Interleukin-11 (IL-11) is a pleiotropic cytokine with important effects on
      hematopoietic and other cells. IL-11 was originally described as a product of
      stromal cell lines and fibroblasts. Using RT-PCR, Northern blotting, and ELISA we
      demonstrated that the human U373 and U87 glioblastoma cell lines expressed IL-11
      and its encoding mRNA when stimulated with IL-1 beta, phorbol ester, and calcium
      ionophore. The neuroblastoma cell line SH-SY5Y did not express IL-11 mRNA in
      response to these agents. Cerebral expression of IL-11 by glial cells is
      important because IL-11 has been shown to have effects on neuronal
      electrophysiology, has overlapping functions with the neuroactive cytokine
      interleukin-6, and is part of the gp130-associated neuropoietic family of
      cytokines.

PMID- 7501272
TI  - Intraperitoneal dizocilpine induces cortical spike-wave seizure discharges in
      rats.
AB  - Dizocilpine has been shown to be anticonvulsant in several experimental models of
      epilepsy. Nevertheless, 0.3 or 0.5 mg/kg intraperitoneal (i.p.) dizocilpine
      produced cortical spike-wave discharges (SWDs) in four of seven rats. The SWDs
      were accompanied by behavioral arrest, and also showed: a narrow range of
      induction times (around 25 min post-injection); hippocampal spikes closely
      correlated with the cortical spikes of the SWDs; a precipitous drop out of fast
      (45-100 Hz) cortical EEG; myoclonic bursts in nuchal EMG that began during the
      cortical slow waves. These findings suggest that patients being treated
      experimentally for stroke with non-competitive N-methyl-D-aspartate (NMDA) cation
      channel blockers should be monitored for seizures.

PMID- 7501273
TI  - Pretreatment with a dopamine D1-receptor antagonist prevents metabolic activation
      by cocaine.
AB  - The pharmacological mechanism underlying metabolic activation of the rat
      extrapyramidal system by acute cocaine was examined using the quantitative 2
      deoxyglucose autoradiographic method. Pretreatment with a selective dopamine D1
      like receptor antagonist, SCH 23390, prevented cocaine-induced metabolic
      activation in the entopeduncular nucleus and substantia nigra pars reticulata in
      a dose-dependent manner. These results suggest that activity in striatonigral
      circuits is induced by stimulation of D1-like receptors by dopamine in the
      presence of acute cocaine.

PMID- 7501274
TI  - Effects of dexamethasone on the epiplexus cells in postnatal rats.
AB  - The epiplexus cells in postnatal rats were markedly reduced in number and
      immunoreactivity for OX-42, OX-18 and ED1 following subcutaneous injections of
      dexamethasone. This was especially evident in rats receiving two or three
      successive injections of dexamethasone and killed at the age of 4 or 7 days. At
      14 and 21 days, the cells did not exhibit any striking difference from their
      corresponding controls in terms of cell number and immunoreactivity for the above
      antibodies. Occasional epiplexus cells were labelled with the antibody OX-6 in
      both groups of rats sacrificed at different time points. In rats receiving
      dexamethasone coupled with rhodamine isothiocyanate (RhIc), the epiplexus cells,
      though fewer in number than the corresponding controls, emitted bright
      fluorescence. It is concluded that the reduction of epiplexus cells following
      dexamethasone injections is due to the suppression of their precursor cells, i.e.
      monocytes. The phagocytic activity of the persisting epiplexus cells did not
      appear to be abolished by dexamethasone as evidenced by their uptake of RhIc. Our
      results suggest that the effects of dexamethasone are reversible.

PMID- 7501275
TI  - Involvement of delta 1-opioid receptors in the antinociceptive effects of
      mexiletine in mice.
AB  - The mechanisms of the antinociceptive effect of mexiletine were assessed by
      administering selective mu-, delta- and kappa-opioid receptor antagonists in
      diabetic and non-diabetic mice. Intraperitoneal administration of mexiletine, at
      doses of 10 and 30 mg/kg, produced dose-dependent antinociception in the tail
      pinch test in both non-diabetic and diabetic mice. The antinociceptive effect of
      mexiletine in diabetic mice was significantly greater than that in non-diabetic
      mice. The antinociceptive effect of mexiletine did not result from the activation
      of mu- or kappa-opioid receptors in either non-diabetic or diabetic mice, since
      treatment with either beta-funaltrexamine, a selective mu- opioid receptor
      antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist,
      was ineffective in blocking mexiletine-induced antinociception. The
      antinociceptive effect of mexiletine was significantly antagonized by
      naltrindole, a selective delta-opioid receptor antagonist, in both non-diabetic
      and diabetic mice. Furthermore, the antinociceptive effect of mexiletine was
      significantly reduced in both non-diabetic and diabetic mice following
      pretreatment with 7-benzylidenenaltrexone, a selective delta 1-opioid receptor
      antagonist, but not with naltriben, a selective delta 2-opioid receptor
      antagonist. These result suggest that delta 1-opioid receptor-mediated mechanisms
      may be involved in the antinociceptive effect of mexiletine.

PMID- 7501276
TI  - The 10-Hz rhythm in the sympathetic nerve activity of cats, rats and rabbits.
AB  - Since the 10-Hz rhythmic activity in the sympathetic nerves was reported only in
      cats, we examined whether the activity of the same frequency could be observed in
      rats and rabbits as well as in the cats. Histograms of inter-burst-peak intervals
      of discharges of the renal nerves revealed that the 100 ms interval activity, the
      reverse of the 10-Hz, was observed in all the three mammals, of which the
      baroreceptor afferents were intact or inactivated. Further, the same frequency
      activity could be evoked by intermittent electrical stimulation of the
      dorsolateral funiculus of the cervical cord in spinal animals. It was suggested
      that the 10-Hz rhythmic activity in the sympathetic nerves was a common
      phenomenon throughout mammals and this activity was produced in the spinal cord.
      The physiological significance of the 10-Hz activity in the sympathetic nerves
      was discussed.

PMID- 7501277
TI  - Sexually dimorphic perforant path long-term potentiation (LTP) in urethane
      anesthetized rats.
AB  - Sex differences in perforant path long-term potentiation (LTP) have been reported
      in pentobarbital-anesthetized rats. Because this effect may be due to the
      prominent sex difference in barbiturate sensitivity, the present report examined
      perforant path-dentate granule cell synaptic transmission and long-term
      potentiation (LTP) in adult male and female rats anesthetized with urethane.
      Spectral analysis of hippocampal electroencephalographic (EEG) activity indicated
      that urethane induced similar levels of anesthesia in male and female rats, and
      there were no sex differences in the latency or amplitude of extracellular field
      potentials evoked in the dentate gyrus following perforant path stimulation. In
      contrast, there was a robust sex difference in the magnitude of LTP induced in
      the dentate gyrus following high-frequency stimulation (HFS) of the perforant
      path. This sex difference in LTP was paralleled by a sex difference in the
      magnitude of N-methyl-D-aspartate (NMDA) receptor activation generated by
      perforant path HFS. These results demonstrate a sex difference in hippocampal LTP
      that cannot be explained by a sex difference in level of anesthesia.

PMID- 7501278
TI  - Induction of transcription factor AP2 mRNA expression in rat primary afferent
      neurons during acute inflammation.
AB  - We have examined immediate early gene mRNA expression, using in situ
      hybridisation in innervating dorsal root ganglion (DRG) neurons following
      peripheral adjuvant injection. Neuronal expression of mRNAs encoding NGFI-A
      (nerve growth factor-induced), NGFI-B, c-jun, jun D and jun B was undetectable in
      untreated controls and was unchanged following adjuvant injection. AP-2 mRNA was
      expressed in the majority of DRG neurons in untreated controls and was
      significantly increased (217 +/- 43% control) 1 h after adjuvant injection. AP2
      mRNA levels returned to control values by 2 h post-injection. AP-2 may form part
      of the early transcriptional response that induces neuropeptide gene expression
      in DRG after adjuvant injection.

PMID- 7501280
TI  - The two types of mRNAs for neurofibromin isoforms produced by von Recklinghausen
      neurofibromatosis (NF1) gene: analysis in human astrocytic tumors.
AB  - Two types of mRNAs for neurofibromin isoforms, which are produced by Von
      Recklinghausen neurofibromatosis (NF1) gene, have so far been identified. In the
      present study, we analyzed the differential expression of the two NF1 mRNAs in 16
      cases of human astrocytic tumors and in surrounding normal tissues by the RNA
      polymerase chain reaction. Astrocytic tumors predominantly expressed type II NF1
      mRNA, whereas it was type I isoform that was predominantly expressed in the
      normal tissues. These results suggested that the increased type II NF1 protein
      might play an important role in the growth of astrocytic tumors.

PMID- 7501279
TI  - Central regulation of micturition in the rat the corticotropin-releasing hormone
      from Barrington's nucleus.
AB  - Barrington's nucleus, a pontine nucleus implicated in micturition, contains
      numerous corticotropin-releasing hormone (CRH) neurons that project to the spinal
      parasympathetic nucleus that innervates the bladder. We now report that CRH from
      Barrington's nucleus may serve to inhibit micturition. Selective chemical
      activation of Barrington's nucleus by microinjection of glutamate evoked bladder
      contractions that were increased in magnitude after intrathecal administration of
      a CRH antagonist, D-PheCRH12-41. In contrast, intrathecally administered CRH
      decreased the magnitude of Barrington's stimulated bladder contractions. These
      results suggest that activation of Barrington's nucleus releases an excitatory
      neurotransmitter responsible for bladder contractions, and CRH, which inhibits
      this neurotransmitter. The balance between these two neuromediators may regulate
      bladder contractility, and thereby, urinary continence.

PMID- 7501281
TI  - Acute administration of angiotensin II improves long-term habituation in the crab
      Chasmagnathus.
AB  - A shadow moving overhead acts as a danger stimulus and elicits an escape response
      in the crab Chasmagnathus granulatus that habituates after 15 trials and for a
      long period. A shorter training of ten trials fails to induce long-term
      habituation; however, a good retention of the habituated response is manifest
      after a 24-h interval when angiotensin II (AII) (10(-6) M, 3 ng/g) is injected
      post-training. By contrast, no amnestic effect of AII was found even though high
      doses were administered. The facilitatory effect of AII is suppressed by
      saralasin (10(-7) M, 0.3 ng/g), a specific angiotensin II receptor antagonist.
      Results are considered as suggesting that angiotensin on memory processes might
      have emerged early in evolution.

PMID- 7501282
TI  - Differential regulation of c-fos, proenkephalin and tyrosine hydroxylase gene
      expression by metrazole in the hamster adrenal and hippocampus.
AB  - Metrazole (MTZ) induces sequential activation of c-fos, proenkephalin (Penk) and
      tyrosine hydroxylase (TH) gene expression in the rat adrenal and c-fos and Penk
      gene expression in the rat hippocampus. As in the rat, MTZ produced a dose
      dependent induction of c-fos mRNA in the hamster adrenal and hippocampus together
      with an increase in adrenal TH mRNA. Although MTZ-induction of preproenkephalin
      (PPenk) mRNA was observed in the hippocampus of the hamster, the same treatment
      failed to induce PPenk mRNA in the hamster adrenal. These results indicate that
      Penk gene expression in the hamster is differentially regulated in the adrenal
      and hippocampus. Furthermore, the regulation of adrenal Penk gene expression
      differs significantly when rat and hamster are compared.

PMID- 7501283
TI  - NMDA R1 mRNA distribution in motor and thalamic-projecting sensory neurons in the
      rat spinal cord and brain stem.
AB  - The N-methyl-D-aspartate (NMDA) receptor is important in both sensory and motor
      neurotransmission. In this study we examine NMDA R1 mRNA hybridization signal
      over individual sensory and motor neurons in the spinal cord and brain stem. A
      significantly greater quantity of NMDA R1 mRNA was present in motor neurons of
      the lumbar spinal cord and hypoglossal nucleus compared to thalamic projecting
      sensory neurons in the spinal cord dorsal horn, the spinal trigeminal nucleus
      pars caudalis and the cuneate and gracile nuclei. No significant difference in
      the quantity of NMDA R1 mRNA was observed between sensory neurons known to relay
      predominantly nociceptive information (trigeminothalamic and spinothalamic tract
      neurons) and that relay predominantly touch and proprioceptive information
      (dorsal column neurons).

PMID- 7501284
TI  - Stimulation of adenosine A2a receptors in the rat striatum induces catalepsy that
      is reversed by antagonists of N-methyl-D-aspartate receptors.
AB  - Bilateral infusion of the selective adenosine A2a agonist CGS 21680C (1 microgram
      per side) into the anterodorsal striatum of rats produced profound catalepsy.
      Intraperitoneal coadministration of the non-competitive N-methyl-D-aspartate
      (NMDA) antagonist dizocilpine (0.16 mg/kg) or the competitive NMDA antagonist CGP
      37849 (4 mg/kg) completely reversed CGS 21680C-induced catalepsy, while lower
      doses of both NMDA antagonists induced no or only weak anticataleptic effects.
      The adenosine A2a receptor localization to striatopallidal neurons suggests that
      a selective activation of the striatopallidal efferent pathway is involved in the
      expression of catalepsy induced by intrastriatal infusion of CGS 21680C. In
      addition, striatopallidal neurons seem to be an important neuronal substrate of
      the anticataleptic effects of NMDA antagonists.

PMID- 7501285
TI  - All pelvic neurons in male rats contain immunoreactivity for the synthetic
      enzymes of either noradrenaline or acetylcholine.
AB  - The pelvic ganglia contain sympathetic and parasympathetic neurons that supply
      the lower urinary and digestive tracts and internal reproductive organs. Although
      synthetic enzymes for noradrenaline have been previously identified in about one
      third of these neurons, until very recently the methodology has not been
      available to directly determine whether all of the remaining neurons are
      cholinergic. The present immunohistochemical study has used a new antibody
      directed against a peptide fragment of choline acetyltransferase (ChAT) to
      identify pelvic cholinergic neurons. The results show that all pelvic neurons are
      either noradrenergic or cholinergic (as seen by the presence of tyrosine
      hydroxylase (TH) or ChAT, respectively). Neurons containing neither or both
      enzymes are extremely rare. It is concluded that the neuropeptides found in most
      pelvic neurons coexist with either noradrenaline or acetylcholine and may be
      involved in cotransmission in the pelvic viscera.

PMID- 7501287
TI  - What patient-focused care gives to nursing.

PMID- 7501286
TI  - Possible modulation of auditory middle latency responses by nitric oxide in the
      inferior colliculus of anaesthetized rats.
AB  - Nitric oxide (NO) is a short-lived radical species endowed with intercellular
      signalling functions in the mammalian brain. In the present study we have
      investigated the effects of focal injection into one inferior colliculus of N
      omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor,
      on the acoustic middle latency responses (MLRs) evoked by click stimuli and
      recorded from the auditory cortex in anaesthetized rats. Microinfusion of L-NAME
      (1.0 mM) did not alter the latency of MLRs nor did it affect the evoked brain
      stem responses (ABRs). By contrast, L-NAME reduced P1a-N1 amplitude of MLRs by
      51.7 +/- 6.6% (mean +/- SEM; n = 5) and almost complete recovery to background
      amplitude was obtained 15-25 min after treatment. The less active isomer, D-NAME
      (1.0 mM; n = 5), failed to produce consistent effects on the evoked MLRs. A
      higher concentration of L-NAME (5.0 mM; n = 5) yielded a 69.0 +/- 13.3%
      inhibition whereas maximum inhibition produced by 0.5 mM (n = 3) L-NAME was
      approximately equal to 10% of control value. The inhibitory effect typically
      evoked by 1.0 mM L-NAME was prevented by treating rats with L-arginine (5.0 mM; n
      = 5), the endogenous precursor of NO synthesis. Reduction of MLR amplitude was
      also obtained in rats receiving intracollicular injection of dizocilpine (MK801;
      1.0 microM) and LY274614 (1.0 mM), two selective N-methyl-D-aspartate (NMDA)
      receptor antagonists. In conclusion, the present data support a role for
      intracollicular NO in the processing and transmission of the acoustic input to
      the auditory cortex in the rat.

PMID- 7501288
TI  - Development and implementation of a program to reduce hospital stays and manage
      resources on a community-wide basis.
AB  - The study describes an effort to reduce hospital stays and limit the use of
      expensive resources in the metropolitan area of Syracuse, New York. The program
      included the implementation of clinical pathways for a number of surgical
      procedures and medical diagnoses. The effort involved the identification of
      specific resource variables in a wide range of clinical disciplines. The program
      was important because it focused on cooperative efforts at length of stay and
      resource reduction by the staffs of all of the hospitals within a common service
      area.

PMID- 7501289
TI  - A cardiac service line approach to patient-centered care.
AB  - The traditionally organized, functionally structured nature of hospitals is no
      longer affordable in today's economic environment. Managed care, the outcomes
      movement, and changed stakeholders have challenged hospitals to become more
      patient centered with seamless, streamlined operations. A service line approach
      focusing on patient populations across a broad continuum of care offers a system
      that maximizes results. Strong leadership that emphasizes a clear vision of the
      future, a process-oriented organizational structure, multidisciplinary clinical
      practice, performance-based management, and broadened roles that emphasize
      lifelong learning have contributed to the success of the cardiac service at
      Virginia Heart Center. Nurse managers have taken the lead at this center in
      achieving superior performance.

PMID- 7501290
TI  - A community hospital redesigns care.
AB  - In response to professional and societal forces, Albany Memorial Hospital
      redesigned patient care services. Funding as a New York State Workforce
      Demonstration project afforded the organization the resources to study components
      such as decentralization of services, case management, and reallocation of work
      to new or expanded roles. Subsequent changes in skill mix were associated with
      improved or unchanged quality indicators and satisfaction levels. Cost savings
      were demonstrated by adjusted labor costs and continue through present housewide
      use of caremapping. Although the process requires tremendous time and energy, the
      outcomes clearly justify the investment.

PMID- 7501291
TI  - Mercy Healthcare's CARE 2000: an evolution in progress.
AB  - In a learning environment of shared governance, continuous quality improvement,
      and redesign principle application, disciplines of Mercy Healthcare San Diego
      produced their patient care delivery redesign model, Creative Actions Reflecting
      Excellence. Nurses, pharmacists, medical technologists, respiratory care
      practitioners, physicians, educators, managers, and many other professional and
      technical partners converted change and transition into opportunities. As
      disciplines understood and appreciated each other's unique and shared
      contributions, quality of care, stakeholder satisfaction, and process
      efficiencies increased.

PMID- 7501292
TI  - Incorporating nursing theory into a nursing department strategic plan.
AB  - Corporations, including health care organizations, have used the strategic
      planning process as a means to plan, coordinate, and direct activities of the
      organization. Research has shown that nursing departments that conduct strategic
      planning perform better. But few nursing departments develop strategic plans. Our
      nursing department recently developed a strategic plan, but the unique aspect of
      our department's plan is the incorporation of nursing theory. This article will
      review the strategic planning process, describe the selection of a nursing theory
      to incorporate into a nursing department strategic plan, and give examples of the
      integration of strategic planning and nursing theory.

PMID- 7501293
TI  - To retool the workplace, you'd better have the right technology tools.

PMID- 7501294
TI  - Generation of masticatory rhythm in the brainstem.
AB  - Mastication is a typical rhythmical behavior in mammals. Like respiration, it is
      now generally accepted that the motor command for the basic pattern of rhythmical
      oral-facial movements is generated by a neuronal population in the brainstem
      (central pattern generator, CPG). The central pattern generation of rhythmical
      masticatory movements can be divided into three processes: (1) generation of the
      masticatory rhythm, (2) generation of a pattern of activities of the jaw, tongue
      and facial muscles, and (3) coordination of the activities of these muscles.
      There are several lines of evidence that the masticatory CPG is functionally
      subdivided into two neuronal groups: one for generation of the masticatory
      rhythm, giving the timing signal for rhythmical alternation of jaw closing and
      jaw opening (central rhythm generator, CRG), and the other for generation of the
      spatiotemporal pattern of activities of the jaw, tongue and facial muscles. This
      review will deal, first of all, with the localization of the CRG for rhythmical
      masticatory jaw movements, sources for its activation, and the premotor neurons
      mediating its output to the trigeminal motoneurons. Next, we will discuss the
      neurochemical basis for rhythmical trigeminal motoneurons activity as well as
      central masticatory rhythm generation. Finally, our recent attempt at induction
      of neural activities reflecting sucking movements (fictive sucking) in an in
      vitro preparation is presented.

PMID- 7501295
TI  - Inspiratory activity responses to lung inflation and ventral medullary surface
      cooling of glossopharyngeal nerve (stylopharyngeal muscle branch) and its
      motoneuron distribution in the rat.
AB  - Inspiratory (I) discharges of the phrenic (Phr) and glossopharyngeal
      (stylopharyngeal muscle branch, IX) nerves were compared in the urethane
      anesthetized, vagi-intact and artificially ventilated rat in which respiratory
      rhythm was generated in synchrony with cyclic changes in airway pressure (P(aw))
      produced by a ventilator. Observations were made during respiratory suppression
      due to excess lung inflation and bilateral cooling of the ventral medullary
      surface (VMS). In the control condition, regular rhythmic I bursts appeared at
      low baseline P(aw) phase (lung deflation) and ceased when P(aw) increased (lung
      inflation) in each ventilator cycle. Increase in baseline P(aw) (P(aw) > 8 cmH2O,
      excess lung inflation) suppressed the initiation of rhythmic I discharge.
      However, threshold baseline P(aw) for suppressing I bursts was higher in the IX
      than in the Phr nerve, and regular rhythmic I activity remained in the IX even
      after cessation of Phr bursts. During VMS cooling, I bursts disappeared first in
      the Phr and subsequently in the IX nerve and emerged always first in the IX
      during recovery. The results suggest that I activity of the IX (stylopharyngeal)
      motoneurons, which are located in the rostral part of the nucleus ambiguus, are
      less suppressed than that of Phr motoneurons by vagal afferents arising probably
      from slowly adapting pulmonary stretch receptors or by a reduction in respiratory
      drive from VMS. These differential responses of Phr and IX motoneurons may be
      ascribed to differences in activation or inhibition processes between two
      motoneuron groups despite both being driven by a common rhythm generator.

PMID- 7501296
TI  - Interaction of the dopaminergic and serotonergic systems in the rat striatum:
      effects of selective antagonists and uptake inhibitors.
AB  - The effects of some selective dopamine (DA) and 5-hydroxytryptamine (5-HT)
      antagonists and uptake inhibitors on the outflow of homovanillic acid (HVA) and 5
      hydroxyindoleacetic acid (5-HIAA) in the striatum were studied using
      microdialysis in conscious rats. Eticlopride (D2 antagonist, 2.5 mg/kg) increased
      HVA but decreased 5-HIAA, while nomifensine (DA uptake inhibitor, 10 mg/kg)
      decreased both. Mianserin (5-HT2 antagonist, 2 mg/kg) and citalopram (5-HT uptake
      inhibitor, 11 mg/kg) also decreased both HVA and 5-HIAA. The selectivity of these
      drugs and the time course of their effects on HVA and 5-HIAA suggested that the
      dopaminergic drugs may affect the serotonergic systems primarily via changes in
      extraneuronal DA and conversely, serotonergic drugs affect the dopaminergic
      systems via changes in extraneuronal 5-HT. The results obtained are consistent
      with current evidence that DA and 5-HT release from striatal terminals are
      regulated by D2 and 5-HT1B autoreceptors, respectively. They also support the
      idea that, in the rat striatum, presynaptic inhibitory heteroreceptors are a
      major mechanism that contributes to a reciprocal interaction of the dopaminergic
      and serotonergic systems.

PMID- 7501297
TI  - A novel factor, TA20, involved in neuronal differentiation: cDNA cloning and
      expression.
AB  - Combined treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) and dibutyryl
      cyclic AMP (diBu-cAMP) induced significantly longer neurites than treatment with
      each alone in NG108-15 cells. We performed differential screening to identify
      genes expressed only by treatment with TPA plus diBu-cAMP but not by that with
      diBu-cAMP for 72 h alone in NG108-15 cells, and isolated a novel gene, TA20. Over
      expression of the gene in NG108-15 and neuroblastoma N18TG-2 cells caused intense
      neurite elongation and suppressed cell growth. TA20 did not cause, however, any
      morphological changes in glioma C6Bu-1 cells. These results suggest that TA20 is
      a novel neuronal differentiation factor.

PMID- 7501298
TI  - Fos expression in the hypothalamic magnocellular neurons of rats during
      pregnancy, parturition and lactation.
AB  - Changes in Fos expression of magnocellular neurons in the supraoptic nucleus
      (SON) and the paraventricular nucleus (PVN) of the rat hypothalamus were
      investigated using immunohistochemistry during pregnancy, parturition and
      lactation. Quantitative morphometrical analysis revealed that Fos-positive cells
      in the hypothalamic magnocellular neurons were rarely seen in days 10 and 20
      pregnant rats, however, significantly numerous Fos-positive cells were found in
      parturient rats. The number of Fos-positive cells was drastically decreased
      within a few days after parturition. Moreover, it was found using dual
      immunohistochemistry that the percentage of Fos-positive cells in vasopressin
      (AVP) magnocellular neurons of the SON was higher than that of the PVN in
      parturient rats, although oxytocin (OXT) magnocellular neurons showed the same
      percentage of Fos-positive cells between the SON and PVN. These results
      demonstrate that the hypothalamic magnocellular neurons express Fos during a
      limited period after parturition, and Fos expression in AVP magnocellular neurons
      is heterogeneous between the SON and PVN.

PMID- 7501299
TI  - Relationship between axonal regeneration and vascularity in tubulation--an
      experimental study in rats.
AB  - This study investigated the effect of vascularity in a nerve conduit on
      peripheral nerve regeneration. The effect of three different types of tube
      (empty, blood vessel-containing and ligated vessel-containing) was compared using
      a rat sciatic nerve preparation with a 10-mm gap. Nerve regeneration through the
      vessel-containing tube was more efficient than in the other tubes 6 and 12 weeks
      after tubulation surgery, but there were no statistically significant differences
      among the three types of tube after 24 weeks. Electrophysiological, histological
      and microangiographic studies showed that vessels which were preinserted in the
      nerve conduit accelerated axonal regeneration through rapid capillary formation
      in the tube.

PMID- 7501300
TI  - Stimulus effects of the medial pontine reticular formation and the mesencephalic
      locomotor region upon medullary reticulospinal neurons in acute decerebrate cats.
AB  - In acute decerebrate cats, medial pontine reticular formation (mPRF) and the
      mesencephalic locomotor region (MLR) were stimulated and their stimulus effects
      upon 250 medullary reticulospinal neurons (RSNs) were studied. One hundred and
      twenty-six RSNs were mono- and disynaptically activated. From the response
      patterns of the RSNs, they were divided into the mPRF-activated RSNs (n = 67) and
      the MLR-activated RSNs (n = 59). The former group of RSNs was located in the
      nucleus reticularis gigantocellularis (NRGc), while the latter group of RSNs was
      distributed in both the NRGc and the nucleus reticularis magnocellularis (NRMc).
      The activity of MLR-excited 12 RSNs was suppressed with the preceding mPRF
      stimulation. These RSNs were mainly located in the NRMc. Most mPRF-excited RSNs
      increased their discharge rates during mPRF-evoked suppression of postural muscle
      tone, and most MLR-excited RSNs increased their discharge rates during MLR-evoked
      locomotion. With mPRF stimulation, MLR-evoked locomotion was suppressed with
      cessation of MLR-excited RSNs activity. These results suggest that mPRF
      stimulation suppresses the activity of the locomotor rhythm generating system at
      the levels of not only the spinal cord but also the medullary output cells.

PMID- 7501301
TI  - Survival of and 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity against
      dopaminergic neurons in coculture of rat mesencephalon with their target on non
      target regions.
AB  - It is known that dopaminergic neurons in the substantia nigra of the
      mesencephalon mainly project to the corpus striatum and neocortex, while the
      hippocampus receives major cholinergic projection from the septum. In the present
      study, the ventral mesencephalon was cocultured with target regions of its
      dopaminergic neurons, the striatum and neocortex, and with non-target regions,
      the hippocampus, thalamus, colliculus and cerebellum, using embryonic day-17
      (E17) rats. Thus, the effects of coculture on the survival and the 1-methyl-4
      phenylpyridnium (MPP+) neurotoxicity of dopaminergic neurons were investigated.
      The numbers of viable dopaminergic neurons were enhanced in coculture not only
      with corpus striatum or neocortex, but also with hippocampus or cerebellum.
      However, the survival of dopaminergic neurons cocultured with thalamus and
      colliculus were almost the same as those of controls. These findings suggest that
      putative factor(s), possibly target-derived neurotrophic factor(s), emerging from
      the regions cocultured with ventral mesencephalon can influence the dopaminergic
      neurons resulting in the augmentation of survival. Cocultivation with all the
      regions studied failed to protect dopaminergic neurons from MPP+ neurotoxicity.
      The results suggest that even though the survival of dopaminergic neurons was
      supported by coculture, the action of MPP+, an exogeneous substance, surpassed
      the supporting capacity of the coculture conditions.

PMID- 7501302
TI  - Identification of differentially expressed mRNAs during neuronal differentiation
      of P19 embryonal carcinoma cells.
AB  - To understand the basic mechanisms underlying neuronal differentiation, we have
      attempted to isolate differentially expressed genes, which may play a key role in
      this complex process, from neuronal differentiating P19 embryonal carcinoma
      cells. RNA fingerprinting by the arbitrarily primed PCR (RAP) method was adapted
      to detect such differentially expressed genes during P19 neuronal
      differentiation. Using this method with some modifications, we successfully
      cloned seven cDNA fragments which were expressed differentially within the first
      48 h after 1 microM retinoic acid (RA) treatment, which ultimately induces
      neuronal differentiation. Comparison of the partial nucleotide sequences of these
      clones with sequences in DNA databases indicated that one of these clones was
      identical to a region of the mouse Oct-3 gene, which has been shown to be
      dramatically repressed by RA. Two clones were highly homologous to the human
      profilinII and leucine-rich protein genes. The other four clones were not closely
      related to any sequences in the databases. Except for the Oct-3 gene, the other
      six genes isolated here have not been reported previously as RA-regulated genes.
      RAP is, thus, a promising method for identification of novel and potentially
      important genes which are differentially regulated during neuronal
      differentiation.

PMID- 7501304
TI  - Fastigiofugal projection to the brainstem nuclei in the cat: an anterograde PHA-L
      tracing study.
AB  - Fastigial projections to brainstem nuclei were studied using an anterograde
      neural tracer, Phaseolus vulgaris leucoagglutinin (PHA-L). Microinjections of PHA
      L were made into the rostral pole, and middle and caudal parts of the left
      fastigial nucleus in cat. In addition to fastigioreticular and fastigiovestibular
      projections, fastigiofugal projections to cranial motor nuclei (IV, VI and VII)
      and those nuclei involved in autonomic control were identified. At the medullary
      level, a topographic arrangement of fastigioreticular projection was observed.
      Rostral and caudal parts of the fastigial nucleus projected to the ventral and
      dorsal parts of the medial reticular formation, respectively. Fastigiofugal
      fibers which originated from the rostral part of the fastigial nucleus innervated
      heavily the nucleus reticularis gigantocellularis (NRGc), nucleus reticularis
      magnocellularis (NRMc) and the ventral paramedian reticular nucleus (PRN). Those
      fibers from the middle part innervated heavily the ventrolateral vestibular
      nucleus (VLV), NRGc, NRMc, ventral and dorsal PRN and parasolitary tract nucleus.
      From the caudal part of the fastigial nucleus, projections to the cranial motor
      nuclei (IV, VI and VII), VLV and inferior vestibular nucleus were observed.

PMID- 7501303
TI  - Chemically defined neuron groups and their subpopulations in the glomerular layer
      of the rat main olfactory bulb.
AB  - Chemically-defined neuron groups and their subpopulations in the glomerular layer
      of the rat main olfactory bulb were revealed immunocytochemically using
      antibodies against gamma-amino butyric acid (GABA), tyrosine hydroxylase (TH),
      methionin-enkephalin-Arg6-Gly7-Leu8 (ENK), calretinin (CR), calbindin-D28K
      (calbindin) and thyrotropin-releasing hormone (TRH). GABA-like immunoreactive
      (GABA-LIR) neurons and CR immunoreactive (CR-IR) neurons were most numerous; they
      were about 1.5-3 times more numerous than calbindin immunoreactive (calbindin
      IR), TH immunoreactive (TH-IR), ENK-like immunoreactive (ENK-LIR) and THR-like
      immunoreactive (TRH-LIR) neurons. We identified at least three distinct
      chemically-defined neuron groups, GABA-LIR neurons, CR containing neurons and
      calbindin containing neurons, since these three neuron groups were almost
      separate from one another. On the other hand, TH-IR and ENK-LIR neurons were
      nearly included in and thus considered to be subpopulations of GABA-LIR and CR-IR
      neurons, respectively, for about 80% of these two neuron groups contained GABA-L
      and CR immunoreactivities, respectively. TRH-LIR neurons appeared to be divided
      into two subpopulations, one containing the GABA-L immunoreactivity and the other
      containing the CR immunoreactivity. Thus in the glomerular layer of the rat
      olfactory bulb, GABA-LIR, CR-IR and calbindin-IR cells could be considered to be
      three distinct chemically-defined neuron groups, whereas TH-IR, TRH-LIR and ENK
      LIR neurons were regarded as their subpopulations. Furthermore, some neurons
      groups, whereas TH-IR, TRH-LIR and ENK-LIR neurons were regarded as their
      subpopulations. Furthermore, some neurons are supposed to contain three
      substances (e.g. GABA + TH + TRH, GABA + TRH + EnK, CR + TRH + ENK, GABA + TRH +
      CR) or a few might even contain four substances (e.g. GABA + TRH + CR + ENK).
      Preliminary quantitative analysis using the optical disector method showed
      percentages of these three main neuron groups to total cells in the glomerular
      layer; that is, neuron groups containing GABA, CR and calbindin were about 20%,
      20% and 10%, respectively.

PMID- 7501305
TI  - The role of energy expenditure in energy regulation: findings from a decade of
      research.
AB  - The role of energy expenditure in energy regulation remains a subject of
      continuing controversy. New data have emerged from studies conducted over the
      last decade demonstrating that energy expenditure is a critical factor
      contributing to successful energy regulation in normal individuals, as well as to
      the disregulation of energy balance that characterizes obesity. Reduced energy
      expenditure appears to facilitate weight gain in individuals susceptible to
      obesity and also appears to reduce the extent of body energy loss during
      undereating in both lean and obese individuals. The magnitude of the reduction in
      energy expenditure during, and perhaps after, weight loss is greater than
      expected on the basis of the reduction in body weight and appears to occur in
      response to undefined underlying determinants of energy regulation. In addition,
      exercise intervention studies and cross-sectional investigations of the
      relationship between energy expenditure for physical activity and body
      composition demonstrate an apparent equilibration between physical activity and
      body fat content. This equilibration is suggestive of a direct influence of
      physical activity on the underlying metabolic determinants of energy balance.

PMID- 7501306
TI  - The development and evolution of U.S. Army field rations.
AB  - Armed conflicts create large masses of personnel that need to be fed nutritious
      foods in less than favorable conditions. The United States military, private
      industry, and academia continue to work together to develop rations that meet the
      needs of military personnel who find themselves in varying climates, conditions,
      and geography.

PMID- 7501307
TI  - A new role for lactoferrin: DNA binding and transcription activation.
AB  - The specific function of lactoferrin, an iron-binding protein found predominantly
      in milk and in granulocytes, is unclear. However, researchers now believe that it
      may modulate immune function. Recent research shows that lactoferrin enters the
      cell from the serum and is transported into the nucleus where it binds DNA.
      Specific DNA sequences that can confer lactoferrin-induced gene transcription of
      a reporter gene have now been identified. This potential direct transcriptional
      function of lactoferrin is unique and remains to be confirmed in whole cells or
      tissues. These observations have great potential for explaining the molecular
      basis for lactoferrin's role in the inflammatory response and in the transfer of
      immunity from mother to child.

PMID- 7501308
TI  - Fish and heart disease: what is the real story?
AB  - A new study shows no significant associations between n-3 fatty acids or fish
      intake and heart disease among men who are initially free of cardiovascular
      disease. These conclusions may somewhat diminish enthusiasm for fish and fish oil
      as a panacea against heart disease.

PMID- 7501309
TI  - A regulatory pathway of thermogenesis in brown fat through retinoic acid.
AB  - Thermogenesis in brown adipose tissue is achieved by the enzyme that uncouples
      the respiratory chain from oxidative phosphorylation. This enzyme is regulated by
      the sympathetic nervous system and, as recently discovered, by transcriptional
      regulation through retinoic acid (RA). Thus, RA is involved in heat production
      and, hence, in the regulation of energy balance.

PMID- 7501310
TI  - The Weight-Control Information Network: a project of the National Institute of
      Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

PMID- 7501311
TI  - Integrating nurse practitioner and nursing roles in a primary health care
      setting.

PMID- 7501312
TI  - International Normalized Ratio (INR): an improved way to monitor oral
      anticoagulant therapy.
AB  - Oral anticoagulant therapy may be inappropriately managed and thus potentially
      place the warfarin-treated patient at an increased and unnecessary risk of
      bleeding or thromboembolic complications. This management issue is largely due to
      variations in measuring the pro-thrombin time. These variations may lead to an
      inaccurate and inconsistent assessment of the patient's true level of
      anticoagulation. The adoption of the International Normalized Ratio (INR) is
      recommended because it provides a mathematical correction for one of these
      variations--specifically, the thromboplastin reagents currently used. This
      article focuses on the appropriate use of the INR to monitor patients' responses
      to warfarin sodium therapy. It is vitally important for health care providers to
      be aware of the INR, to use it in clinical practice, and to interpret it
      correctly.

PMID- 7501313
TI  - Respiratory syncytial virus in infants and children.
AB  - Respiratory syncytial virus (RSV) is a frequent cause of respiratory illness in
      infants and children, affecting almost 100% of children by the age of 3 years.
      Mild RSV infection usually involves only the upper respiratory tract, while the
      lower respiratory tract is involved in severe disease. This article addresses the
      epidemiology of RSV infection, transmission of the disease, predisposing
      conditions, clinical course, diagnosis, and management. The majority of children
      can be managed on an outpatient basis, while some will require hospitalization.
      Outpatient management, with a focus on adequate hydration, humidification, and
      comfort measures, is emphasized with a brief overview of the management of the
      hospitalized patient. Breast-feeding, crowded conditions, and hand washing are
      discussed relative to primary and secondary prevention.

PMID- 7501314
TI  - Preventing influenza and its complications: a public health initiative for the
      year 2000.
AB  - Influenza remains a significant cause of morbidity and mortality among the
      elderly and persons with certain chronic illnesses. Despite the availability of
      safe and efficacious immunization against the virus, only a small percent of
      persons at-risk for complications are immunized annually. This article describes
      influenza virus, indications for influenza vaccination, chemoprophylaxis and
      treatment of influenza, and strategies for practitioners to increase immunization
      rates among at-risk individuals.

PMID- 7501315
TI  - Nurse practitioners in a teaching hospital.
AB  - The development of a model of care using acute care nurse practitioners in a
      teaching hospital and the integration of the nurse practitioner into an
      alternative model of care delivery are discussed. Issues in implementation
      include lack of understanding about the nurse practitioner role on the part of
      other members of the health care team, legislative constraints, and the
      administrative restrictions of teaching hospitals. Education of nurses and
      physicians regarding the scope of practice of the nurse practitioner role,
      departmental policy changes, and the development of protocols facilitate the
      efficiency and utilization of the nurse practitioner in this setting. Specific
      concerns surrounding costs of a nurse practitioner service and practice
      differences between the clinical nurse specialist and the acute care nurse
      practitioner are addressed. Nurse practitioner models of care delivery, which
      address quality, cost-effective care are on the forefront of tomorrow's health
      care.

PMID- 7501316
TI  - Adult urinalysis screening.

PMID- 7501317
TI  - Bacterial overgrowth in a patient with chronic diarrhea.
AB  - A case study is presented of a 47-year old, white female with a 1-year
      progressive history of diarrhea up to 20 liquid stools per day, accompanied by an
      18-pound weight loss. She had presented with previous workup of gastroscopy
      revealing two stomach ulcers; colonoscopy revealing nonspecific colitis and one
      polyp that was subsequently removed and found to be benign; and a negative
      abdominal ultrasound. She was Helicobacter pylori negative and HIV negative. Her
      stools had been negative for blood, ova and parasites, and culture. She had been
      using well water from a new well for 2 years. String test was negative for
      Giardia. She had no diarrhea during a day of fasting. Carbon 14 D-xylose breath
      test was positive. She was discharged on a 14-day course of 500 mg. Augmentin
      (amoxicillin 500 mg. with clavulanate potassium 125 mg.) by mouth every 8 hours.
      Seven weeks later, she was having four to five formed stools per day and had
      gained 16 pounds.

PMID- 7501318
TI  - New antidepressants.

PMID- 7501319
TI  - Adenomyosis--an ignored uterine disease.

PMID- 7501320
TI  - DNA takes the stand.

PMID- 7501321
TI  - The association between manual removal of the placenta and postpartum
      endometritis following vaginal delivery.
AB  - OBJECTIVE: To determine whether manual removal of the placenta after vaginal
      delivery is a risk factor for postpartum endometritis. METHODS: A retrospective
      cohort study of vaginal deliveries compared 1052 patients who had manual removal
      of the placenta with 1085 patients whose placentas delivered spontaneously.
      Subjects were selected randomly from the 25,687 vaginal deliveries at the
      University of Iowa Hospitals during 1979-1992. The presence of endometritis was
      determined using information in medical records. The data were analyzed using
      odds ratios (OR) and multiple logistic regression. RESULTS: After controlling for
      confounding variables, manual removal of the placenta was associated with
      postpartum endometritis (adjusted OR 2.9, 95% confidence interval [CI] 1.7-4.9).
      Other risk factors for endometritis included maternal age less than 17 years (OR
      3.3, 95% CI 1.5-7.2), postpartum anemia (OR 2.9, 95% CI 1.9-4.5), and membranes
      ruptured longer than 24 hours (OR 2.5, 95% CI 1.4-4.3). CONCLUSION: Manual
      removal of the placenta is a risk factor for postpartum endometritis after
      vaginal delivery.

PMID- 7501322
TI  - Vaginal endosonography in the assessment of the anorectum.
AB  - Endosonography from within the anus has been used to image the anorectum and its
      associated musculature. A 5.0-MHz endovaginal probe was inserted vaginally, and
      longitudinal and cross-sectional views of the anorectum were obtained. We were
      able to measure rectal length and diameter, puborectalis thickness and angle,
      thickness of internal and external anal sphincter, and the curvature of the anal
      canal. We visualized defects in the internal and external anal sphincters.
      Suitable images were obtained from 70 subjects. Muscle thicknesses were within
      previously published ranges. Twenty-five of 70 subjects (36%) had defects of the
      internal anal sphincter, and 19 of 65 subjects (29%) had defects of the external
      anal sphincter.

PMID- 7501323
TI  - Is salpingostomy the surgical treatment of choice for unruptured tubal pregnancy?
AB  - Salpingostomy has gradually replaced salpingectomy as the surgical procedure of
      choice for unruptured tubal pregnancy in women who wish to preserve fertility.
      There are no prospective studies and only a few retrospective reports comparing
      fertility rates after salpingostomy and salpingectomy. Three major retrospective
      studies found no significant difference in fertility or incidence of repeat
      ectopic pregnancy between the two procedures, but salpingostomy carries a 5-8%
      risk of persistent ectopic pregnancy, contributing to increased morbidity and
      cost. There are approximately 109,000 ectopic pregnancies per year in the United
      States. If half are treated by salpingostomy, 54,500 women will need serial beta
      hCG testing after surgery. Approximately 3543 will have a persistent ectopic
      pregnancy requiring surgical or medical treatment. The additional direct costs
      created by persistent ectopic pregnancy is estimated to be almost $16,000,000.
      Fertility after ectopic pregnancy is affected much more by the status of the
      contralateral tube than by the procedure performed, with fertility rates
      exceeding 80% after salpingectomy when the opposite tube is normal. By performing
      salpingectomy when the contralateral tube is normal, half the additional cost and
      morbidity could be avoided without jeopardizing subsequent fertility.

PMID- 7501324
TI  - The cost of teaching residents outpatient obstetrics and gynecology in a
      university medical center.
AB  - OBJECTIVE: To quantify the cost of teaching residents ambulatory obstetrics and
      gynecology, expressed as the difference in revenue generated between a faculty
      physician practicing as a private practitioner and a faculty physician serving as
      a resident supervisor. METHOD: Outpatient revenue generated by faculty
      generalists and residents was analyzed. The net gain in revenue was calculated
      per half-day session for faculty and residents by subtracting contractual
      allowances and expenses from gross patient charges. Net revenue gain per half-day
      clinical session per year for a faculty member practicing as a private
      practitioner was compared with that of a faculty member functioning as a
      supervisor. The net gain for the faculty supervisor was based on the revenue
      generated by the residents supervised. RESULTS: The faculty member serving as a
      private practitioner generated a net gain per session per year of $23,947. The
      faculty member acting as supervisor for two residents per session generated a net
      gain or loss per session per year of -$9678, -$972, and $15,542 for first-,
      second-, and third-year residents, respectively. The cost of teaching, expressed
      as the difference in the net gain of a faculty member as private practitioner and
      the net gain of a faculty member as supervisor, for first-, second-, and third
      year residents was $33,625, $24,919, and $8405, respectively, per session per
      year. CONCLUSION: This analysis shows that first-year residents are an expense to
      the practice site, second-year residents are close to breaking even, and third
      year residents begin to generate a net gain.

PMID- 7501325
TI  - Current trends in obstetric and gynecologic academic faculty manpower.
AB  - Five prior academic manpower studies were completed by ACOG and the Association
      of Professors of Gynecology and Obstetrics in 1977-1990. In the current survey, a
      similar questionnaire was sent to the 130 accredited medical school departments
      of obstetrics-gynecology; 127 responded. The mean number of full-time faculty
      members per department is 25.8, an increase of 14% over the last 4 years. Among
      faculty, women constitute 30.4%, an increase of five percentage points since
      1990. Certified subspecialists on faculties have increased 27% in the last 4
      years, but decreasing percentages of all subspecialists are in faculty positions
      compared with private practice settings. Chairmen remain optimistic about
      continued faculty growth despite the inroads of managed care.

PMID- 7501326
TI  - Amoxicillin or erythromycin for the treatment of antenatal chlamydial infection:
      a meta-analysis.
AB  - OBJECTIVE: To compare the effectiveness of amoxicillin and erythromycin for the
      treatment of antenatal Chlamydia trachomatis infection by meta-analysis of
      available trials involving random assignment of subjects. DATA SOURCES: A
      computer search of English-language abstracts using MEDLINE and the Cochrane
      Pregnancy and Childbirth Database (medical subject heading terms: pregnancy,
      chlamydia, erythromycin, amoxicillin, antenatal antibiotics) was supplemented
      with a review of the bibliographies of the relevant articles generated by the
      computer search. METHODS OF STUDY SELECTION: Five trials were identified, four of
      which met our inclusion criteria for the meta-analysis. DATA EXTRACTION AND
      SYNTHESIS: Trials to be included in this meta-analysis underwent trial quality
      evaluation and data abstraction. An estimate of the relative risk (RR) was
      calculated for the dichotomous outcomes using a fixed-effects model. The pooled
      RR for the effectiveness of amoxicillin compared with erythromycin was 1.11 (95%
      confidence interval [CI] 1.05-1.18), and the pooled RR for gastrointestinal side
      effects of amoxicillin compared with erythromycin was 0.29 (95% CI 0.20-0.42).
      The pooled RR for gastrointestinal side effects that resulted in discontinuation
      of therapy of amoxicillin compared with erythromycin was 0.14 (95% CI 0.06-0.36).
      CONCLUSION: The available data suggest that amoxicillin is more effective than
      erythromycin for the treatment of antenatal C trachomatis infection and has fewer
      gastrointestinal side effects, leading to better compliance.

PMID- 7501327
TI  - The myomatous erythrocytosis syndrome: a review.
AB  - OBJECTIVE: To review the literature regarding the association of erythrocytosis
      and uterine myomas, because of the lack of anemia in many women with menorrhagia
      and fibroids. DATA SOURCES: We searched the MEDLINE English-language data base
      and reference lists to find articles referring to the myomatous erythrocytosis
      syndrome. METHODS OF STUDY SELECTION: All case reports of the myomatous
      erythrocytosis syndrome were included in this review. DATA EXTRACTION AND
      SYNTHESIS: Symptoms, laboratory studies, histopathologic findings, and possible
      etiologies for each of 31 cases were extracted. The symptoms described were most
      commonly related to the presence of a myomatous uterus with occasional
      manifestations of erythrocytosis. A routine complete blood count was used to
      diagnose erythrocytosis in all cases. Evaluation of the bone marrow, blood
      volume, erythrocyte life span, and erythropoietin activity have all been used to
      help confirm the diagnosis. The histopathologic findings were similar to those
      commonly seen in myomas. Possible factors in the etiology of this syndrome
      include: vascular shunts within the myoma, large uterine size, myoma site, change
      in red cell life span, alteration in erythropoietin production by the kidney, and
      autonomous secretion of erythropoietin or an erythropoietin-like substrate by the
      myomatous uterus. CONCLUSION: Elevated levels of erythropoietin accompany the
      myomatous erythrocytosis syndrome. All myomas may alter erythropoietin
      production, causing varying degrees of erythrocytosis, which could explain the
      lack of anticipated anemia despite the presence of menorrhagia. Use of the
      currently available, highly sensitive radioimmunoassay for erythropoietin should
      help in our understanding of the role uterine myomas play in erythropoiesis.

PMID- 7501328
TI  - Clinical research in ancient Babylon: methodologic insights from the book of
      Daniel.
AB  - Around 600 BC, Daniel of Judah conducted what is widely regarded as the earliest
      recorded clinical trial. His trial compared the health effects of a vegetarian
      diet with those of a royal Babylonian diet over a 10-day period. The strengths of
      his study include the use of a contemporaneous control group, use of an
      independent assessor of outcome, and striking brevity in the published report.
      Weaknesses include probable selection bias, ascertainment bias, and confounding
      by divine intervention. Although Daniel probably never achieved tenure, he did
      get "learning and skill in all letters and wisdom ... and understanding in all
      visions and dreams" (well before Freud). Despite the trial's dramatic findings,
      over 4 centuries elapsed before publication of Daniel's results. Daniel
      apparently perished, then published.

PMID- 7501329
TI  - Adverse pregnancy outcome after a false-positive screen for Down syndrome using
      multiple markers.

PMID- 7501330
TI  - A decrease from 8 to 6 weeks in obstetrics and gynecology clerkship: effect on
      medical students' cognitive knowledge.

PMID- 7501331
TI  - Intentional delivery versus expectant management with preterm ruptured membranes
      at 30-34 weeks' gestation.
AB  - OBJECTIVE: To determine maternal and neonatal outcomes in pregnancies complicated
      by preterm rupture of membranes (PROM) at 30-34 weeks' gestation. METHODS: A
      randomized controlled trial was conducted to study the benefits of expectant
      management in women hospitalized for PROM at 30-34 weeks' gestation. During this
      investigation, no tocolytics, corticosteroids, or prophylactic antibiotics were
      used. RESULTS: Sixty-eight women with PROM were managed expectantly and 61 were
      delivered intentionally. The mean gestational age at study entry was 31.7 weeks
      in both the expectant management and intentional delivery groups (P > .05). The
      mean gestational ages at delivery were similar (32.0 and 31.7 weeks,
      respectively). Other indices of pregnancy outcome (ie, birth weight,
      intraventricular hemorrhage, necrotizing enterocolitis, sepsis, respiratory
      distress syndrome, and perinatal death) were not significantly improved by
      expectant management. However, there was a significant increase in the incidence
      of chorioamnionitis and antepartum hospitalization in the women managed
      expectantly. CONCLUSION: There were no clinically significant neonatal advantages
      to expectant management of ruptured membranes at 30-34 weeks. Antepartum
      hospitalization was decreased by 2.5 days in those women randomized to
      intentional delivery.

PMID- 7501332
TI  - A randomized trial of two preparations of vaginal prostaglandin for pre-induction
      cervical ripening.
AB  - OBJECTIVE: To compare two prostaglandin (PG) E2 preparations for pre-induction
      cervical ripening in a randomized clinical trial. METHODS: Two milligrams of
      vaginal PGE2 gel was compared with a vaginal PGE2 3-mg tablet in 200 nulliparous
      women. Outcomes assessed were induction failure, need for labor augmentation,
      pain relief requirements, fetal heart rate (FHR) abnormalities, operative
      delivery rate, induction-to-delivery interval, neonatal condition, and occurrence
      of uterine hyperstimulation. RESULTS: There was no statistical difference in pre-
      and post-dose cervical scores. Compared with the tablet group, women in the gel
      group were more likely to have significant FHR abnormalities in early labor (odds
      ratio [OR] 4.77, 95% confidence interval [CI] 1.15-19.5) requiring cesarean
      delivery. Fetal heart rate tracings in the active phase of labor were also more
      likely to be abnormal in the gel group (chi 2 = 4.31, P < .05). Compared with the
      gel group, women in the tablet group were significantly more likely to require
      operative delivery for poor progress in labor (OR 2.83, 95% CI 1.20-7.24). Other
      clinical outcomes were identical, with no significant differences in the overall
      rate of failed induction, cesarean delivery, rate of assisted delivery,
      requirement for oxytocin infusion, induction-to-delivery interval, pain relief
      requirements, or neonatal condition. CONCLUSIONS: When compared with the PGE2
      tablet, the use of PGE2 gel for cervical ripening and labor induction in
      nulliparous women did not result in significant improvements in labor outcome.
      Whereas the gel was associated with an increase in significant FHR abnormalities,
      the tablet was associated with an increase in the rate of operative delivery for
      poor progress in labor.

PMID- 7501334
TI  - Efficiency of lower threshold criteria for the diagnosis of gestational diabetes.
AB  - OBJECTIVES: To determine the incidence of adverse outcome in normal untreated
      gravidas with minimal hyperglycemia, classified as having gestational diabetes
      mellitus (GDM) by threshold criteria lower than current standards; to determine
      how efficient the different criteria are in identifying infants at risk for
      morbidity; and to explore the pathophysiology of minimal hyperglycemia using the
      glucose tolerance test (GTT) periodicity concept. METHODS: Seven hundred eight
      subjects considered nondiabetic by current ACOG criteria were reclassified by the
      criteria of Coustan (fasting 95, 1 hour 180, 2 hours 155, and 5 hours 140 mg/dL),
      Sacks (96, 172, 152, and 131 mg/dL), or Langer (at least one abnormal ACOG
      value). Glucose tolerance test periodicity, the incidence of large for
      gestational age (LGA) neonates, and macrosomia were then determined for each
      gravida diagnosed as having GDM by these criteria. RESULTS: Both Coustan and
      Langer criteria identified a significantly greater incidence of LGA infants
      compared with non-GDM (23.6 and 25.3%, respectively, versus 14%, P < .05), and
      identified them as efficiently as current criteria, approximately one LGA infant
      for every four GDM subjects treated. The incidence of LGA did not differ between
      the Sacks GDM and non-GDM groups. Glucose tolerance test periodicity for newly
      diagnosed GDM gravidas was significantly longer than non-GDM for Coustan and
      Langer criteria (3.9 and 4.06 versus 3.3 hours, P < .01) but not for the Sacks
      criteria. CONCLUSION: Using lower threshold criteria to diagnose GDM identified
      morbidity at an incidence and efficiency comparable to current standards. These
      newly diagnosed GDM gravidas had abnormal GTT characteristics, with each group
      exceeding the 3.5-hour GTT periodicity limit previously found for nondiabetic
      gravidas. Sack's conversion of existing standards may be too low to efficiently
      identify pregnant subjects at risk for increased morbidity.

PMID- 7501336
TI  - Decreased maternal serum hCG levels with increasing gravidity and parity.
AB  - OBJECTIVE: To investigate the preliminary observation that primigravid women have
      higher hCG multiples of the median (MoM) than multigravid women. METHODS: An
      analysis of the effect of gravidity and parity on maternal serum alpha
      fetoprotein (MSAFP) and hCG was performed using data from 20,009 consecutive
      singleton pregnancies of 15-20 weeks' gestation in a maternal serum screening
      program. RESULTS: The human chorionic gonadotropin MoM for primigravid women was
      0.1 MoM higher than for multigravid women. As parity or gravidity increased,
      maternal serum hCG decreased. The median hCG MoM for nulliparous women was 1.05,
      compared with 0.94 MoM for para 3 women. The decrease in hCG was similar at each
      gestational week from 15-20. In contrast, MSAFP and MSAFP MoM were unaffected by
      parity. Maternal age and race were potential contributing factors to the effect
      of parity. However, the decrease in hCG MoM with parity was observed within each
      5-year increment of maternal age. Similarly, both black and non-black populations
      displayed decreases in hCG with parity, although black women had a consistently
      higher MoM in all matched sets. The decrease in hCG MoM with parity was also
      observed in 50 Down syndrome cases. Correcting patient data for parity resulted
      in the hCG MoM changing only 2.7% on average. The detection rate for the 50 Down
      syndrome cases would not have changed. CONCLUSION: The decrease in maternal serum
      hCG with increasing parity demonstrates that pregnancy history influences the
      level of maternal serum hCG. Further studies are needed to define the
      contributing factors, but the impact of parity on Down syndrome screening appears
      to be small.

PMID- 7501335
TI  - Thrombomodulin levels in preeclampsia, gestational hypertension, and chronic
      hypertension.
AB  - OBJECTIVE: To measure the circulating levels of thrombomodulin in women with
      preeclampsia, gestational hypertension, and chronic hypertension. METHODS: Serum
      levels of thrombomodulin were measured in 34 women with preeclampsia, 15 with
      gestational hypertension, 11 with chronic hypertension, and 34 normotensive
      pregnant women in the third trimester. Preeclampsia, gestational hypertension,
      and chronic hypertension were defined by ACOG criteria. Soluble thrombomodulin
      antigen was measured by a two-site enzyme-linked immunosorbent assay. RESULTS:
      Mean (+/- standard error) serum thrombomodulin levels were significantly higher
      in patients with preeclampsia (69.7 +/- 6.3 ng/mL) than in those with gestational
      hypertension (46.0 +/- 3.2 ng/mL) or chronic hypertension (46.2 +/- 3.3 ng/mL),
      and normotensive controls (50.1 +/- 3.1 ng/mL). There were no significant
      differences among the gestational hypertension, chronic hypertension, and
      normotensive control groups. CONCLUSION: Thrombomodulin may serve as a clinically
      meaningful marker to differentiate preeclampsia from other forms of hypertensive
      disorders in pregnancy.

PMID- 7501333
TI  - Prospective cohort study of the effect of pregnancy on the progression of human
      immunodeficiency virus infection. The Groupe d'Epidemiologie Clinique Du SIDA en
      Aquitaine.
AB  - OBJECTIVE: To study the prognostic role of pregnancy on the progression of human
      immunodeficiency virus (HIV) infection. METHODS: In a prospective cohort study at
      the Bordeaux University Hospital, France, 57 women who completed a pregnancy
      during the course of their HIV infection were compared with 114 HIV-infected
      women who never conceived. The two groups were matched on CD4 lymphocyte count
      (CD4), age, and year of HIV diagnosis. The main outcome measures were death,
      occurrence of a first AIDS-defining event, and drop of the CD4 below 200/mm3.
      RESULTS: The mean follow-up period in pregnant women was 61 months from HIV
      diagnosis (median CD4 at entry 455/mm3) and 54 months from beginning of
      pregnancy. Nonpregnant women were followed-up for 50 months since HIV diagnosis
      (median CD4 460/mm3). The proportion of asymptomatic women at entry in the study
      was 51 of 57 (90%) in pregnant and 87 of 114 (76%) in nonpregnant women. No
      significant difference was observed between the two groups with regard to the
      different end points studied, even after adjustment for other prognostic
      variables. Adjusted hazard ratios (pregnant/nonpregnant) were 0.92 for death (95%
      confidence interval [CI] 0.40-2.12), 1.02 for occurrence of a first AIDS-defining
      event (95% CI 0.48-2.18), and 1.20 for drop of the CD4 to less than 200/mm3 (95%
      CI 0.63-2.27). CONCLUSION: In a cohort of HIV-infected women with mild to
      moderate immunosuppression, pregnancy did not accelerate progression to AIDS or
      death.

PMID- 7501337
TI  - Singleton pregnancy after in vitro fertilization: expectations and outcome.
AB  - OBJECTIVE: To determine if singleton in vitro fertilization (IVF) pregnancies
      carry a higher risk for ante- and perinatal complications compared with naturally
      conceived pregnancies. METHODS: One hundred forty singleton pregnancies conceived
      by IVF and 140 matched control pregnancies conceived naturally were analyzed with
      respect to the incidence of antepartum complications and perinatal outcome. The
      study was conducted in a university hospital, and pregnancy and labor were
      managed according to a standardized protocol. RESULTS: Sixteen IVF pregnancies
      and two control pregnancies ended preterm (P < .01), resulting in the birth of
      infants with lower birth weight in the former group (P = .01). Except for
      placenta previa, which occurred four times in IVF pregnancies and not in the
      control group, no differences in antenatal events were found. Labor was more
      often induced in IVF pregnancies than in control pregnancies. Elective cesarean
      delivery for obstetric reasons was performed ten times in the IVF group and never
      in the controls (P < .01). However, once in labor, no differences in the rate of
      instrumental or cesarean delivery were found. There were eight minor congenital
      malformations in the IVF group and none in the control group (P < .01).
      CONCLUSION: Even when managed in a single center, IVF pregnancies carry a greater
      antenatal risk than matched controls. Once in labor, and managed in a similar
      fashion, the outcome does not differ from that of controls.

PMID- 7501338
TI  - The efficacy and safety of subcutaneous sumatriptan in the acute treatment of
      menstrual migraine. The Sumatriptan Menstrual Migraine Study Group.
AB  - OBJECTIVE: To compare the efficacy and safety of subcutaneous sumatriptan with
      placebo in the treatment of menstrual migraine. METHODS: A double-blind, placebo
      controlled, parallel group study was conducted to assess the efficacy and safety
      of subcutaneous sumatriptan in the treatment of menstrual migraine over two
      attacks. A total of 179 subjects received sumatriptan or placebo to treat at
      least one menstrual migraine attack. RESULTS: The efficacy results were
      consistent for attacks one and two. Two hours after treatment in attacks one and
      two, 53 (73%) and 51 (81%) of the sumatriptan-treated subjects, respectively,
      reported headache relief (reduction of a severe or moderately severe headache to
      a mild or no headache), compared with 27 (31%) and 18 (29%) of the placebo
      treated subjects (P < .001). Within 24 hours of treatment in attack one, 28 (53%)
      and 14 (52%) of the initial responders to sumatriptan and placebo, respectively,
      experienced headache recurrence. The incidence and nature of adverse events in
      this study were similar to that seen in previous studies. CONCLUSIONS:
      Subcutaneous sumatriptan is an effective and well-tolerated acute treatment for
      menstrual migraine.

PMID- 7501340
TI  - Vaginal correction of pelvic organ relaxation using local anesthesia.
AB  - OBJECTIVE: To describe the technique and complications of vaginal repair of
      advanced pelvic organ prolapse using intravenous sedation, pudendal nerve block,
      and local anesthesia. METHODS: A retrospective review of the gynecologic surgical
      records of 20 patients was performed. Patient demographics, surgical procedure,
      surgical time, estimated blood loss, and complication rate were examined.
      RESULTS: All 20 patients reviewed had their operations completed without the need
      for general anesthesia. The surgical procedures included three anterior
      colporrhaphies, five anterior and posterior colporrhapies, eight vaginal
      enterocele repairs with anterior and/or posterior repair, and four LeFort partial
      colpocleises. General anesthesia was contraindicated in all patients. Patients
      had a mean age of 80 years (range 67-92), a mean parity of 2.7, a mean estimated
      blood loss of 153 mL, and a mean hospital stay of 2.1 days. One intraoperative
      and three postoperative complications were reported. CONCLUSION: All 20 patients
      had successful surgical repair under local anesthesia without the need for
      general induction. Surgical correction of severe pelvic organ relaxation can be
      performed rapidly and safely using local anesthesia, thus limiting the potential
      risks of general anesthesia.

PMID- 7501341
TI  - Effect of Candida albicans infection and clotrimazole treatment on vaginal
      microflora in vitro.
AB  - OBJECTIVE: To determine the effect of Candida albicans infection and clotrimazole
      treatment on vaginal microflora. METHODS: Studies were conducted using a model
      simulating the healthy vaginal ecosystem. The model consisted of a mixed culture
      of Lactobacillus acidophilus, Staphylococcus epidermidis, Prevotella bivia, and
      group D Streptococcus sp grown in continuous culture in a chemically defined
      medium. The status of the model was assessed using a mathematical equation that
      determines the probability a microflora is normal or abnormal. RESULTS: Challenge
      of the model with C albicans was followed within 24 hours by the development of
      microbial populations representing an abnormal microflora. Treatment of the
      system with clotrimazole (100 micrograms/mL) resulted in a decrease in C albicans
      counts to 0 within 48 hours. However, treatment also altered other components of
      the vaginal microflora, which did not return to normal. Addition of clotrimazole
      (100 micrograms/mL) to the system in the absence of C albicans also resulted in
      an abnormal model by 24 hours. CONCLUSIONS: Candida albicans infection of the
      vaginal ecosystem, as represented by this in vitro model, has a deleterious
      effect on members of the normal microflora. Clotrimazole, although effective
      against C albicans infection, also has a deleterious effect on components of the
      normal vaginal microflora. One of the implications for women using clotrimazole
      for microbiologically undocumented vaginal yeast infections is an increased risk
      of infection or disease through the disruption of the protective microflora
      barrier.

PMID- 7501342
TI  - Cervical dilation from laminaria tents and synthetic osmotic dilators used for 6
      hours before abortion.
AB  - OBJECTIVE: To compare thick laminaria tents with two synthetic osmotic devices
      for softening and dilating the cervix before abortions. METHODS: This was a
      randomized clinical trial comparing cervical dilation by thick laminaria tents
      with two commercially made devices, 3-mm Hypan and 3-mm anhydrous magnesium
      sulfate-impregnated plastic tents, used for 6 hours. Subjects were 7-14 weeks
      pregnant, and all 93 were assigned to devices in permuted randomized groups of
      three. Physicians and patients were not blinded to the type of device used. Need
      for a tenaculum for insertions, ease of introduction, cramps, removal ease,
      hourglassing, achieved dilation, and ease of forced dilation were compared. The
      effects of parity and gestational length on achieved dilation were also analyzed.
      RESULTS: Parity did not affect dilation. Significant positive, linear slopes of
      regression were found for achieved dilation versus weeks of gestation for thick
      laminaria tents and magnesium sulfate devices but not for Hypan tents. Forcible
      dilation was easiest with thick laminaria tents and most difficult with magnesium
      sulfate devices. CONCLUSION: All devices provided safe cervical dilation and
      softening, but thick tents were most effective.

PMID- 7501339
TI  - Interference with uterine blood flow by clomiphene citrate in women with
      unexplained infertility.
AB  - OBJECTIVE: To investigate the effect of clomiphene citrate on the uterine blood
      flow in women with unexplained infertility. METHODS: Twenty-one women who had
      normal uterine blood flow (pulsatility index [PI] less than 3 from the LH peak to
      the middle luteal phase of a natural ovulatory cycle) were enrolled in this
      study. Patients were given clomiphene citrate (100 mg/day) from days 5-9 of the
      next ovulatory cycle. The PI values measured in the natural and clomiphene
      citrate-treated cycles were compared using repeated measures analysis of
      variance. Their correlations with the estradiol (E2) and progesterone
      concentrations in the treatment cycle were calculated using the Pearson
      correlation coefficient. RESULT: In the natural cycles of those with normal
      uterine blood flow, the highest impedance of uterine blood flow was detected at
      the late follicular phase, then blood flow increased during the luteal phase. In
      the clomiphene citrate-treated cycles, a statistically significant decrease in
      uterine blood flow also occurred during the early luteal phase (P < .05). No
      significant correlation of E2 or progesterone serum concentrations with PI values
      of the uterine artery could be found in either natural or clomiphene citrate
      treated cycles. CONCLUSION: The use of clomiphene citrate decreases the uterine
      blood flow during the early luteal phase, a periimplantation stage.

PMID- 7501343
TI  - Myometrial estradiol and progesterone receptor changes in preterm and term
      pregnancies.
AB  - OBJECTIVE: To determine if labor is associated with changes in myometrial
      estradiol (E2) and progesterone receptors. METHODS: Lower myometrial segments
      were obtained from women undergoing cesarean deliveries at term in labor (n =
      10), term not in labor (n = 10), preterm in labor (n = 9), and preterm not in
      labor (n = 11). Western immunoblotting was used to determine the presence and
      molecular size of E2 and progesterone receptor proteins. Immunocytochemistry was
      used to determine E2 and progesterone receptor changes in preterm and term
      pregnancies. RESULTS: Myometrium from pregnant women contained 74-kilodalton
      (kDa) E2 receptor and 94- and 110-kDa progesterone receptor proteins. These
      receptors are present in both myometrial smooth muscle and myometrial blood
      vessels. The nuclei of myometrial smooth muscle cells primarily contain both
      receptors. The immunostaining for progesterone receptors was less in patients in
      labor compared with those not in labor in preterm and term pregnancies. In
      comparing patients not in labor, the immunostaining for progesterone receptors
      was less at term compared with preterm pregnancy. Unlike the differences in
      progesterone receptors, there are no obvious differences in E2 receptor
      immunostaining in myometrial samples from all four groups of women. CONCLUSION: A
      myometrial decrease in progesterone receptors, rather than an increase in E2
      receptors, may play a role in the onset of labor in women with term or preterm
      pregnancies.

PMID- 7501345
TI  - Vaginal anatomy and sexual function.
AB  - OBJECTIVE: To describe vaginal anatomy related to sexual function in women.
      METHODS: One hundred four women presenting for gynecologic care (mean age 55.8
      years) completed questionnaires assessing sexual function and underwent
      measurements of vaginal caliber and length, and grading of vulvovaginal atrophy.
      RESULTS: Women who were not currently sexually active had a higher mean body mass
      index. Current sexual activity was not associated with differences in vaginal
      length or introital caliber. Among 73 sexually active women, 30 had one or both
      symptoms of dyspareunia and vaginal dryness, and 43 had neither symptom.
      Menopausal status, current use of estrogen, introital caliber, and vaginal length
      were not different in women with dyspareunia, vaginal dryness, or both when
      compared to women having neither symptom. Premenopausal women with dyspareunia,
      vaginal dryness, or both had significantly higher global sexual function scores,
      reflecting worse sexual function, when compared with premenopausal women without
      these symptoms (0.61 +/- 0.16 versus 0.46 +/- 0.15, respectively; P = .02);
      however, there was no significant difference in postmenopausal women (0.60 +/-
      0.12 versus 0.61 +/- 0.12). CONCLUSION: Vaginal anatomy, measured by introital
      caliber, length, and vulvovaginal atrophy, does not correlate well with sexual
      function, particularly symptoms of dyspareunia and vaginal dryness.

PMID- 7501344
TI  - The effectiveness of hysterectomy for chronic pelvic pain.
AB  - OBJECTIVE: To evaluate the effectiveness of hysterectomy in treating chronic
      pelvic pain, and to identify risk factors for persistent pelvic pain. METHODS: A
      group of 308 women who had hysterectomy for chronic pelvic pain of at least 6
      months' duration was followed-up for 1 year after surgery, as part of a large,
      prospective, multicenter cohort study. Persistent pain was defined as a
      trichotomous variable, and ordinal logistic regression was used to identify
      independent predictors of the trichotomous outcome. RESULTS: Overall, 74% of
      women experienced complete resolution of pelvic pain, 21% reported continued but
      decreased pain, and 5% reported either unchanged or increased pain after
      hysterectomy. In unadjusted analyses, women at increased risk for persistent pain
      (eg, continued but decreased, and unchanged or increased) included those who were
      under age 30 (36 versus 22%, P < .05), had a history of pelvic inflammatory
      disease (41 versus 25%, P < .05), were uninsured or covered under Medicaid (41
      versus 22%, P < .001), had no identified pelvic pathology (38 versus 23%, P <
      .05), or had a history of at least two pregnancies (31, 27, and 15% for those
      with at least four, two or three, and one or none, respectively; P < .05). After
      adjustment, an increased probability of persistent pain was observed among women
      who had no identified pelvic pathology (odds ratio [OR] 1.9, 95% confidence
      interval [CI] 1.0-3.6), were uninsured or covered under Medicaid (OR 2.3, 95% CI
      1.2-4.3), or had experienced at least two pregnancies (OR 2.3, 95% CI 1.0-5.3).
      CONCLUSION: Most women with chronic pelvic pain have long-term improvement after
      hysterectomy. However, up to 40% of women in specific subgroups may continue to
      experience long-term pain.

PMID- 7501346
TI  - Improvement of perineal sonographic bladder neck imaging with ultrasound contrast
      medium.
AB  - OBJECTIVE: To assess the efficacy of ultrasound contrast medium when imaging
      bladder neck anatomy in perineal ultrasound. METHODS: In 39 women with clinically
      and urodynamically proven urinary stress or stress-urge incontinence, a new
      echogenic contrast medium (Echovist) was administered transurethrally and
      perineal ultrasound was performed. Women were examined in the upright position
      both without and with ultrasound contrast medium at rest and during Valsalva
      maneuver, and the pictures of the bladder base, bladder neck, and urethra were
      compared. RESULTS: With the subject in the upright position, the contrast medium
      lay at the lowest point of the bladder and resulted in a reverse picture of the
      bladder base and bladder neck and clear visualization of these structures. In
      women with urinary stress incontinence, the ultrasound contrast medium entered
      the urethra during Valsalva, and bladder neck funneling was identified more
      accurately than without contrast medium. With Echovist, bladder neck funneling
      was detected in 38 of the 39 cases, compared with only 19 when it was not used.
      Furthermore, when the bladder neck, urethra, or bladder base were not visible
      with plain perineal ultrasound, they were seen when ultrasound contrast medium
      was used. The contrast agent was well tolerated, and there were no adverse side
      effects. CONCLUSION: The use of ultrasound contrast medium improves visualization
      of the bladder neck anatomy. Bladder neck funneling and urinary leakage are seen
      more distinctly, and this improves the diagnostic reliability in female urinary
      stress incontinence.

PMID- 7501347
TI  - The efficacy of cranial irradiation in ovarian cancer metastatic to the brain:
      analysis of 32 cases.
AB  - OBJECTIVE: To determine the role of irradiation in the management of brain
      metastases from epithelial ovarian cancer. METHODS: Tumor registries from five
      university cancer centers were searched to identify ovarian cancer patients with
      brain metastases. During a 30-year period (1965-1994), 4027 ovarian cancer
      patients were evaluated, 32 of whom were found to have cerebral metastases. Each
      received fractionated whole-brain irradiation (median dose 30 Gy, range 20-52.5).
      Five patients received concomitant chemotherapy with whole-brain irradiation.
      RESULTS: The median survival time for the whole population was 4 months. For the
      entire series, symptomatic response (complete response and partial response) was
      achieved in 23, 16 of whom were palliated until death. Patients with higher
      Karnofsky performance status (70 or above versus below 70) were more likely to
      derive a palliative response and attained a statistically significant survival
      advantage. No other factor predicted the likelihood of deriving a palliative
      response or a survival advantage after treatment. CONCLUSIONS: In this large
      review of patients with cerebral metastases from ovarian cancer, we found that
      most of those treated with whole-brain irradiation achieved palliation until
      death. Nearly all women with high performance status derived durable palliation
      from cerebral irradiation. Whole-brain irradiation was an effective means of
      palliating ovarian cancer metastatic to the brain and provided a favorable
      alternative to other means of management.

PMID- 7501348
TI  - Drainage following radical hysterectomy and pelvic lymphadenectomy: dogma or
      need?
AB  - OBJECTIVE: To compare the incidence of lymphocyst formation and postoperative
      morbidity in patients drained or not drained following radical hysterectomy and
      pelvic lymph node dissection for cervical or endometrial malignancy. METHODS: A
      prospective study was undertaken of consecutive patients undergoing radical
      hysterectomy and pelvic lymphadenectomy at the Regional Department of
      Gynaecological Oncology, Gateshead, United Kingdom, between February 1992 and
      September 1994. A Piver type II procedure was performed with nonclosure of the
      vaginal cuff and pelvic peritoneum. Patients were randomized at the end of
      surgery to have either two suction drains inserted along the pelvic sidewalls or
      to have no drains inserted. The detection of lymphocysts was made by clinical
      examination and abdominal ultrasound scan performed 8 weeks postoperatively.
      RESULTS: Eight patients were excluded from the study when drains were deemed
      necessary to assess postoperative blood loss. Fifty-one were randomized to
      drains, and 49 to no drains. The detection of lymphocysts by ultrasound and
      clinical examination in the drained group (15.6 and 5.9%, respectively) was not
      significantly different from the group not drained (17.4 and 6.1%, respectively).
      There was no difference in postoperative morbidity in the two groups. CONCLUSION:
      There appears to be no advantage to the routine use of pelvic suction drainage
      following radical hysterectomy and pelvic lymphadenectomy.

PMID- 7501350
TI  - Expectant management of twin pregnancies discordant for anencephaly.
AB  - OBJECTIVE: To study the clinical course and perinatal outcome of twin pregnancies
      discordant for anencephaly, without selective termination. METHODS: We conducted
      a descriptive retrospective study of 14 cases of dichorionic twin pregnancies
      discordant for anencephaly, which were managed expectantly in five Israeli
      perinatal centers. RESULTS: None of the patients miscarried. The mean gestational
      age at delivery was 35.9 +/- 2.8 weeks (range 29-39). Only three patients (21%)
      delivered before 35 weeks' gestation. Polyhydramnios occurred in six of the
      anencephalic amniotic sacs. Nevertheless, most occurrences were mild and none
      necessitated therapeutic amniocentesis. The mean birth weight of the normal fetus
      was 2610 +/- 690 g (range 1100-3200). One apparently normal twin had a cardiac
      anomaly and died shortly after birth, and one was electively delivered at 33
      weeks because of severe intrauterine growth retardation and subsequently
      developed cerebral palsy. The rest had normal short- and long-term outcomes.
      CONCLUSION: Expectant management of a twin gestation discordant for anencephaly
      diagnosed at the second trimester is associated with a favorable outcome for the
      unaffected fetus.

PMID- 7501349
TI  - Laparoscopic management of adnexal masses in women with a history of
      nongynecologic malignancy.
AB  - OBJECTIVE: To describe the safety and efficacy of laparoscopy in the diagnosis
      and treatment of patients with a history of nongynecologic malignancy presenting
      with an adnexal mass. METHODS: A retrospective review of the records of all
      patients with a history of nongynecologic malignancy who underwent laparoscopy
      for adnexal masses at our institution in 1992-1994. RESULTS: Thirty-four patients
      were identified. The mean age was 57.3 years (range 32-85). Twenty-five had
      breast cancer, three had malignant melanoma, and two had lymphoma; the remaining
      four had lung, colon, stomach, and pancreatic cancer, respectively. Thirty of the
      34 cases (88%) were managed laparoscopically; unilateral or bilateral salpingo
      oophorectomy was performed in 22, laparoscopically assisted vaginal hysterectomy
      in three, ovarian cystectomy in three, and pelvic washings in two. In these
      cases, the adnexal disease was benign in 24 and metastatic cancer in six. In all
      the metastatic cases, preoperative ultrasound or computed tomography scan
      revealed complex and/or solid adnexal masses. Six complications occurred in the
      34 cases; two of 25 patients who had D&C had uterine perforation, two patients
      had subcutaneous hematomas at laparoscopic puncture sites, one had a bowel
      obstruction, and one developed pneumonia after laparotomy. CONCLUSION:
      Laparoscopy proved to be safe and effective in the initial surgical evaluation of
      patients with a history of a nongynecologic malignancy presenting with an adnexal
      mass. Most patients can be spared the added morbidity and convalescence
      associated with laparotomy. This laparoscopic approach should be considered the
      initial method of surgical evaluation in this population.

PMID- 7501351
TI  - Acute and chronic fetal hypoxia in monochorionic and dichorionic twins.
AB  - OBJECTIVE: To assess the risk for acute and chronic fetal hypoxia in twin
      pregnancies. METHODS: We investigated 50 sets of twins (24-38 weeks' gestation,
      660-3200 g birth weight) admitted consecutively to our neonatal intensive care
      unit. Seventy-six infants were appropriate for gestational age (AGA; tenth to
      90th percentile), 20 were small for gestational age (SGA; below the tenth
      percentile), and four were large for gestational age (above the 90th percentile).
      Twenty-six singleton AGA term newborns served as controls. Umbilical arterial pH
      was used as a marker for acute and umbilical venous erythropoietin concentration
      for chronic fetal hypoxia. The results are given as median followed by quartiles.
      RESULTS: We identified 40 sets of diamniotic-dichorionic twins and ten sets of
      diamniotic-monochorionic twins with transplacental vascular shunts. In the second
      born twin, umbilical arterial pH was lower (7.29, 7.23-7.33) than in the
      firstborn (7.31, 7.25-7.34) (P = .03), and the incidence of a low pH (less than
      7.20) was higher (19 versus 11%). Two second-born twins and none of the firstborn
      twins had an umbilical arterial pH less than 7.05. In SGA twins, the
      erythropoietin concentration was elevated (34.8, 22.8-325 mU/mL) compared with
      that in AGA twins (16.2, 8.2-26.6 mU/mL) (P < .01). In AGA twins, erythropoietin
      concentration did not differ from that in AGA singleton newborns (19.6, 14.7-31.6
      mU/mL). In 12 of 17 twin sets with weight discordancy greater than 15% and in all
      five twin sets with weight difference greater than 25%, erythropoietin
      concentration was higher in the smaller twin. The proportion of infants and of
      complete sets with elevated erythropoietin levels was higher (P < .01) in
      monochorionic than in dichorionic pregnancies. CONCLUSION: The second-born twin
      is at increased risk for acute birth asphyxia. Fetal growth restriction in twin
      pregnancies is associated with chronic fetal hypoxia. Monochorionic twins are at
      higher risk for chronic fetal hypoxia than are dichorionic twins.

PMID- 7501352
TI  - Obstetric clavicular fracture: the enigma of normal birth.
AB  - OBJECTIVE: To determine the main risk factors involved in neonatal clavicular
      fracture, the most common injury to the neonate. METHODS: Two hundred fifteen
      cases of clavicular fracture of 65,091 vaginal deliveries (0.4%) occurring
      between January 1983 and December 1988 were pair-matched with controls based on
      mode and date of delivery, race, and maternal age. Incidences, odds ratios, and
      stratified analysis were used to identify and control for confounding between
      risk factors. RESULTS: Shoulder dystocia, increasing birth weight, and increasing
      gestational age were identified as risk factors. Within the range of normal birth
      weights, there is a biologic gradient of increasing risk for clavicular fracture.
      Although shoulder dystocia is the strongest risk factor identified, the magnitude
      of its point estimate is probably affected to a large extent by differential
      ascertainment. The use of forceps, prolonged second stage of labor, and
      nulliparity status were not significantly associated with neonatal clavicular
      fracture. CONCLUSIONS: Neonatal clavicular fracture occurs commonly in an
      obstetric population. Obstetric clavicular fracture is an unpredictable,
      unavoidable complication of normal birth.

PMID- 7501353
TI  - The effect of combined antenatal vitamin K and phenobarbital therapy on umbilical
      blood coagulation studies in infants less than 34 weeks' gestation.
AB  - OBJECTIVE: To determine if antenatal vitamin K and phenobarbital therapy affect
      coagulation studies in umbilical blood at birth, and to provide 95% reference
      ranges for umbilical blood coagulation parameters in premature gestations.
      METHODS: Patients at imminent risk for spontaneous or indicated premature
      delivery less than 34 weeks' gestation were randomized to receive either placebo
      or vitamin K and phenobarbital. Prothrombin time (PT), activated partial
      thromboplastin time (PTT), functional coagulation factors, and decarboxylated
      prothrombin assays were performed on umbilical blood specimens. Decarboxylated
      prothrombin, also known as "protein induced by vitamin K absence-factor II" or
      precursor prothrombin, is a sensitive marker for vitamin K deficiency.
      Standardized values of PT and PTT are reported in seconds and standardized values
      of factor assays in percentage of normal adult functional activity (mean +/- one
      standard deviation). RESULTS: Newborns in the placebo and treatment groups had
      similar umbilical blood PT (12.6 +/- 1.2 versus 12.7 +/- 1.4 seconds), PTT (48.8
      +/- 13.4 versus 49.6 +/- 13.8 seconds), and functional activity of factor II
      (40.3 +/- 12.5 versus 42.0 +/- 12.1%), factor VII (67.0 +/- 20.9 versus 66.8 +/-
      18.9%), factor IX (27.4 +/- 12.8 versus 25.8 +/- 8.9%), and factor X (47.0 +/-
      12.8 versus 49.2 +/- 11.6%). Newborns in the treatment group were about half as
      likely as those in the placebo group to have detectable decarboxylated
      prothrombin levels in umbilical blood at birth (gestational age-adjusted odds
      ratio 0.47, 95% confidence interval 0.22-1.01; P = .05). CONCLUSIONS: Combined
      maternal therapy with vitamin K and phenobarbital before premature delivery does
      not affect umbilical blood PT, PTT, or functional activity of vitamin K-dependent
      coagulation factors II, VII, IX, and X. However, it is associated with the
      reduced presence of decarboxylated prothrombin in umbilical blood at birth. There
      is significant improvement in umbilical blood coagulation tests as gestational
      age advances from 24 to 34 weeks.

PMID- 7501354
TI  - Sonographic estimation of umbilical coiling index and correlation with Doppler
      flow characteristics.
AB  - OBJECTIVE: To quantitate umbilical vascular coiling antenatally, and to correlate
      the coiling index with Doppler flow characteristics in umbilical vessels.
      METHODS: We studied 45 normal term fetuses within 24 hours before delivery. The
      umbilical coiling index was calculated using sonographic longitudinal views of
      cord vessels from several segments antenatally, and by dividing the total number
      of helices by the cord length (in centimeters) postnatally. Doppler flow
      velocities were obtained from umbilical arteries and vein in each cord. Flow
      characteristics were correlated with the umbilical coiling index. RESULTS: The
      mean (+/- standard deviation) umbilical coiling index was 0.44 +/- 0.11 in the
      antepartum period and 0.28 +/- 0.08 after birth. Regression analysis showed a
      significant linear trend (r = 0.71, P < .001). The correlations between
      sonographic coiling index and umbilical arterial Doppler flow characteristics
      (mean velocity, pulsatility index, resistance index, and systolic-diastolic
      ratio) were not significant. The sonographic coiling index was related to time
      averaged velocity and flow in the umbilical vein. A good correlation was found
      between umbilical vein flow and the coiling index, with a significant linear
      trend (r = 0.59, P < .001). CONCLUSION: An intrauterine umbilical coiling index
      can be determined by ultrasound and correlates well with the actual index at
      birth. The sonographic umbilical coiling index is related to Doppler flow
      characteristics in the umbilical vein.

PMID- 7501355
TI  - Nuchal translucency measurement in normal fetuses.
AB  - OBJECTIVE: To construct a normal range for the nuchal translucency measurement in
      chromosomally and phenotypically normal fetuses between 9 and 14 weeks'
      gestation. METHODS: The nuchal translucency was measured prospectively in 771
      chromosomally normal fetuses of women attending our antenatal clinic or prenatal
      diagnosis center. The nuchal translucency measurement was expressed as the median
      and fifth, 25th, 75th, and 95th percentiles according to completed weeks of
      gestation based on ultrasound measurements. RESULTS: The median nuchal
      translucency measurement increased from 0.7 mm at 10 weeks' gestation to 1.5 mm
      at 13 weeks. A nuchal translucency measurement greater than 2.5 mm was found in
      4.6% of the fetuses at 10 weeks' gestation; the incidence increased to 8.7% at 14
      weeks. CONCLUSION: In normal fetuses, there is a physiologic variation in the
      nuchal translucency measurement between 9 and 14 weeks' gestation. The
      calculation of risk for trisomies based on this measurement should take this
      variation into account. The adoption of a gestational age-dependent cutoff point,
      based on the deviation of a given measurement from the median, may reduce the
      number of false-positive test results requiring invasive procedures for
      karyotyping.

PMID- 7501357
TI  - The Theiler Memorial Trust Award. Dr Walter Plowright.

PMID- 7501358
TI  - The detection of antibodies cross-reacting with Cowdria ruminantium in the sera
      of domestic ruminants in regions of South Africa where Amblyomma hebraeum does
      not occur.
AB  - High levels of seropositivity, in all probability attributable to Ehrlichia, were
      recorded in the serum of domestic ruminants throughout districts in South Africa
      where Amblyomma hebraeum, the vector of the heartwater agent, does not occur. The
      antibodies, detected with the indirect fluorescent antibody (IFA) and the
      indirect ELISA tests, cross-reacted with Cowdria ruminantium, which was used as
      antigen in both tests. A combination of the IFA and ELISA tests, currently
      employed to detect antibodies to C. ruminantium, facilitates the handling of
      appreciable numbers of sera and ensures maximum reliability.

PMID- 7501356
TI  - Echogenic intracardiac focus: a sonographic sign for fetal Down syndrome.
AB  - OBJECTIVE: To determine whether an echogenic intracardiac focus identified in the
      second-trimester fetus is related to an increased risk of Down syndrome. METHODS:
      During a 10-month period, all women with singleton gestations who underwent
      second-trimester genetic amniocentesis for non-imaging indications were evaluated
      prospectively by prenatal sonography. The presence or absence of an echogenic
      intracardiac focus was noted. Karyotypic information was obtained on each fetus.
      RESULTS: Among the 1334 patients in the study group, 66 fetuses (4.9%) had an
      echogenic intracardiac focus. Four of 22 fetuses (18%) with trisomy 21 had an
      echogenic intracardiac focus, compared with 62 (4.7%) of 1312 fetuses without
      Down syndrome who also had an echogenic intracardiac focus (P = .004).
      Sonographic identification of an echogenic intracardiac focus was associated with
      a fourfold increased risk of Down syndrome (risk ratio 4.3, 95% confidence
      interval 1.5-12.3). The overall prevalence of Down syndrome in our study
      population was 1.6%. The sensitivity, specificity, and positive predictive value
      for using the presence of an echogenic intracardiac focus to identify a fetus
      with Down syndrome was 18.2, 95.3, and 6.1%, respectively. Extrapolating to a
      lower risk population, the positive predictive value of an echogenic intracardiac
      focus for detecting Down syndrome in patients at an age-based risk of one in 250,
      one in 500, and one in 1000 was calculated to be 1.53, 0.77, and 0.39%
      respectively. CONCLUSION: Fetuses with an echogenic intracardiac focus have a
      significantly increased risk of Down syndrome. Although most fetuses with this
      finding are normal, patients carrying fetuses with an echogenic intracardiac
      focus should be counseled about the increased risk of trisomy 21.

PMID- 7501360
TI  - Isolation and preliminary characterization of a caprine rotavirus.
AB  - Five cytopathic rotavirus strains were isolated in MA104 cells from stool
      specimens of kids with diarrhoea. Pre-treatment of the virus with trypsin and
      incorporation of low levels of trypsin in the maintenance medium were important
      for the successful cultivation of the strains in these cells. The isolates were
      shown to be group A rotaviruses by antigenic reactivity with a group A monoclonal
      antibody. This was confirmed by the migration patterns of the viral RNA genome
      during polyacrylamide gel electrophoresis, which also confirmed that all five
      strains had an identical RNA electropherotype. Analysis with monoclonal
      antibodies to the subgroup-specific VP6 antigen showed that these strains carried
      the subgroup I epitope.

PMID- 7501359
TI  - Evidence for cryptosporidial infection as a cause of prolapse of the phallus and
      cloaca in ostrich chicks (Struthio camelus).
AB  - Cloacas of male ostrich chicks that had suffered prolapse of the phallus and
      cloaca were compared with cloacas of normal ostrich chicks of both sexes from the
      same area. Heavy infection of the cloacal and bursal tissue with Cryptosporidium
      sp. was present in all the cases of prolapse, while no cryptosporidia were
      observed in the normal chicks. Histopathological lesions as described in
      cryptosporidial infection in other species were present in the infected cloacas.
      These included loss of the microvillous border and epithelial hyperplasia and
      degeneration, which was indicated ultrastructurally by vacuolation of the apical
      cytoplasm, swelling of organelles, and nuclear changes. It is suggested that
      these lesions, in combination with the anatomy of the male ostrich cloaca, may be
      responsible for prolapse of the phallus and cloaca.

PMID- 7501361
TI  - A survey of the incidence and importance of the tick-borne diseases heartwater,
      redwater and anaplasmosis in the heartwater-endemic regions of South Africa.
AB  - In an almost 50% response to a survey questionnaire, farmers in the heartwater
      endemic regions of South Africa indicated that they were experiencing losses of
      1.3, 0.3 and 0.2% in cattle due to heartwater, redwater and anaplasmosis,
      respectively. In small stock, the heartwater mortality was 3.8%. Only 35% of
      cattle farmers and 15% of farmers keeping sheep and goats, vaccinate their
      animals against heartwater. It would seem that the present vaccine does not
      control heartwater adequately and, with 9% of farmers claiming poor protection
      after immunization, it would be difficult to recommend wider use of the
      heartwater vaccine. Likewise, vaccination against redwater and anaplasmosis on
      11.8 and 14.2% of farms, respectively, appears to have had no beneficial effect
      on the mortality rates of these diseases. Many farmers still believe that very
      few or no ticks should be seen on cattle. In fact, it would appear that a
      considerable proportion of farmers find so few ticks on their cattle, that the
      frequency of acaricidal treatment is in many cases too high. Although there is no
      correlation between the incidence of heartwater and the intensity of tick
      control, there is also no serological evidence to support the possibility of an
      endemically unstable condition. The concept that endemic stability as a means to
      control heartwater in cattle can be achieved by allowing more ticks on animals,
      has not yet been established. The overall impression is that farmers do not
      regard heartwater in cattle as such a serious problem as it is generally believed
      to be.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501362
TI  - Vanadium air pollution: a cause of malabsorption and immunosuppression in cattle.
AB  - An epidemiological investigation into an "illthrift" problem occurring on a dairy
      farm adjacent to an alloy-processing unit, established that the probable cause of
      the problem was chronic vanadium poisoning. The disease manifested initially in
      animals 4-18 months old which showed emaciation, chronic diarrhoea and, in some
      cases, rhinitis, conjunctivitis and recumbency followed by death. Post-mortem (n
      = 17) and clinical-pathology findings (n = 60) indicated that malabsorption and
      immunosuppression were the basis of the pathogenesis in affected animals. Eight
      months after the commencement of the investigation, adult cows began showing
      evidence of emaciation, reduced milk production and an apparent increase in the
      number of abortions, stillbirths and dystocias. Over a 2-year period, 134 surface
      soil samples, 134 subsoil samples and 134 grass samples from the farm were
      analysed for various fractions of vanadium. Thirty-four of each of these samples
      were collected at different time intervals (autumn 1990, summer 1991 and winter
      1991) and at varying distances and directions from the processing unit, in order
      to gauge the magnitude of the problem, and the distribution pattern of vanadium,
      and to identify possible seasonal trends. The remaining 100 of each of these
      samples were taken at 100-m intervals over an area of approximately 1,140,000 m2
      directly adjacent to the processing unit so that concentration isolines for
      vanadium could be drawn and the source more conclusively identified. The levels
      of vanadium were found to be highest closest to the mine, and surface-soil levels
      were consistently higher than subsoil levels, suggesting aerial pollution, which
      was confirmed by air sampling.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501363
TI  - A bioequivalence and pharmacokinetic evaluation of two commercial diminazene
      aceturate formulations administered intramuscularly to cattle.
AB  - The bioequivalence of the diminazene formulation Veriben (Centaur) was determined
      in cattle (n = 10) by means of a single-dose, randomized cross-over experiment.
      The results of nine statistical procedures commonly used for bioequivalence
      evaluation are discussed. Veriben was found to be equivalent to Berenil (Hoechst)
      with respect to the area under the plasma concentration versus time curve, but
      not in terms of the maximum plasma drug concentration and the time to maximum
      plasma drug concentration. Pharmacokinetic parameters were calculated in which
      bioequivalence data (n = 10) together with data from an additional four cattle
      were used. A two-compartment model best described the pharmacokinetic behaviour
      of diminazene in cattle. Peak concentrations of diminazene (3.24 +/- 0.16
      micrograms/ml) were reached 49.8 (+/- 7.6) min after intramuscular injection of
      3.5 mg/kg drug, with absorption proceeding rapidly (t1/2 alpha = 1.93 +/- 0.95
      h). Diminazene was slowly eliminated (t1/2 beta = 222 h), resulting in a mean
      residence time of 13.27 d. The safe interval necessary between successive
      treatments of diminazene or before live babesia vaccines should be administered,
      and a recommended pre-slaughter withdrawal period are also discussed.

PMID- 7501364
TI  - The virtual absence of Culicoides imicola (Diptera: Ceratopogonidae) in a light
      trap survey of the colder, high-lying area of the eastern Orange Free State,
      South Africa, and implications for the transmission of arboviruses.
AB  - Altogether 52 078 Culicoides biting midges of 35 species were collected during
      February 1990 and 1993 in 40 light-trap collections made on 17 cattle and/or
      sheep farms in the Bethlehem and Fouriesburg districts of the colder, high-lying
      eastern Orange Free State. Culicoides (Avaritia) bolitinos was by far the most
      abundant species, representing 50.9% of all specimens collected. Culicoides (A.)
      imicola, considered to be the most common stock-associated species in the summer
      rainfall areas of southern Africa, and the only proven vector of bluetongue virus
      (BTV) and African horsesickness virus (AHSV) in the subregion, was uncommon,
      comprising only 1.4%. While AHS is apparently absent, BT and bovine ephemeral
      fever (BEF) are endemic in this cooler, high-lying area of South Africa. The
      virtual absence of C. imicola implies that other Culicoides species, such as C.
      bolitinos and C. cornutus, may be involved in transmitting BT virus (and perhaps
      BEF) in the eastern Orange Free State, and possibly elsewhere in Africa. Virus
      isolation attempts made on 45 single species pools of C. bolitinos, C.
      pycnostictus, C. milnei, C. leucostictus, C. zuluensis and C. gulbenkiani were,
      however, negative. Finally, 20 of 28 blood-engorged Culicoides of 11 species,
      which were tested against cattle, sheep, horse, pig and bird antisera, tested
      only positive against cattle antisera.

PMID- 7501365
TI  - A rapid method to quantify bacterial contamination on hatching eggs. 1.
      Correlation of optical density with initial bacterial count.
AB  - The use of optical-density (OD) readings after a 6-h incubation period, as a
      suitable method to quantify the bacterial contamination on hatching eggs, was
      established by the use of pure cultures of five bacterial isolates found to be
      the most prevalent on the hatching eggs examined. These isolates were identified
      as Micrococcus luteus, Staphylococcus gallinarum, Streptococcus epidermidis,
      Pseudomonas cepacei and Bacillus cereus. It was established that the OD reading
      was repeatable when the same inoculum was used to inoculate five different
      cultures, which were incubated for 6 h at 37 degrees C. This repeatability was
      not affected by bacterial isolate, or bacterial concentration of the inoculum, or
      when mixed bacterial cultures were used. A direct relationship was established
      between the OD reading (at 540 nm) after 6 h and the log of the bacterial
      concentration at the start of incubation. The OD reading after 6 h of incubation
      is a repeatable, rapid and simple method to quantify the bacterial concentration
      at the start of the incubation period.

PMID- 7501366
TI  - Photosensitivity in South Africa. VIII. Ovine metabolism of Tribulus terrestris
      saponins during experimentally induced geeldikkop.
AB  - Geeldikkop was induced in a sheep by dosing it orally with a crude extract of the
      steroidal saponins from Tribulus terrestris. GC-MS analysis of the sheep's
      ruminal contents, bile, faeces and urine for free and conjugated sapogenins,
      revealed the general features of the metabolic pathway by which diosgenin and
      yamogenin glycosides were converted into the glucuronides of epismilagenin and
      episarsasapogenin, the major constituents of the biliary crystals that usually
      form during geeldikkop. Other steroidal saponins in the T. terrestris extract,
      including those derived from tigogenin, neotigogenin, gitogenin and neogitogenin
      appear to be non-lithogenic. The implications of these findings are discussed.

PMID- 7501367
TI  - Understanding tsetse flies.
AB  - The discovery that tsetse flies are the vectors of African trypanosomosis,
      causing sleeping sickness in man and nagana in cattle, occurred at the start of a
      rapidly expanding colonialism in sub-Saharan Africa. Hence, the first research on
      the fly was largely taxonomic, coupled with a painstaking ecological approach to
      determine the identities and distribution limits of the different species. This
      was followed by closer attention to the physiology of the fly, both from the
      academic standpoint as related to its survival and reproduction in the field, and
      from the standpoint of its vectorial capacity. There are still conflicting
      hypotheses concerning the maturation of trypanosomes within the fly. Increasing
      concern for the environment led to a ban in the developed nations on the use of
      DDT as an insecticide which had been used successfully for tsetse control in
      Africa. This was followed by a ban on the use of organochlorine insecticides in
      general, and no doubt the next restrictions will be on the use of
      organophosphates and upon synthetic pyrethroids which have already been banned in
      the UK for the control of houseflies. Fortunately, research on the role of
      olfactory and visual stimuli of the tsetse, in the location of potential hosts,
      led to an improvement in methods for monitoring fly populations by means of traps
      and targets upon which the flies alight. So successful are such devices that,
      when treated with an insecticide, they can be used to sustain an increase in
      natural mortality in fly populations to such an extent that these populations
      decline to manageable levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501368
TI  - Sleeping sickness and the central nervous system.
AB  - Chronic African trypanosomiasis is associated with progressive behavioural
      deficits, for which there is a complex underlying central nervous system (CNS)
      pathology. This has been extensively studied in man and a range of experimental
      animals. An initial meningitis, which can occur quite early in the infection, is
      followed by a breakdown of the choroid plexus, movement of the parasite into
      certain localized brain areas, and subsequent encephalitis. The encephalitis
      consists of a chronic, widespread inflammation with perivascular infiltrations of
      B-cells, plasma cells, inactivated T-cells and macrophages. The blood-brain
      barrier is damaged and a vasogenic oedema ensues. Astrocytes and microglia become
      reactive and the cytokine/mediator network is perturbed. The alterations in some
      of these signalling substances, e.g. the prostaglandins, may induce some of the
      behavioural changes, e.g. the hypersomnia. The immunopathology in the CNS may be
      brought about by elevated levels of active substances in the cerebrospinal fluid,
      caused by parasite infection.

PMID- 7501369
TI  - The impact of nagana.
AB  - The disease in cattle, called nagana in Zululand, was linked with trypanosomal
      parasitaemia and tsetse flies. Nagana occurs in livestock throughout the tsetse
      belts of Africa. Wild animals are tolerant of trypanosomal infections. Nagana
      affects individual animals, herds and socio-economic development. In susceptible
      animals nagana may be acute, but chronic infections are more common. The host
      parasite interaction produces extensive pathology and severe anaemia. Clinically
      affected animals lose condition and become weak and unproductive. Nagana is often
      fatal and, at herd level, its impact is wide ranging. All aspects of production
      are depressed: fertility is impaired; milk yields, growth and work output are
      reduced; and the mortality rate may reduce herd size. Africa has to feed its
      rapidly growing human population, and animal products are a vital dietary
      component. However, in most tsetse areas, there is not enough meat and milk.
      Furthermore, animal draft power is often not available, which limits cultivation
      and local transport. These factors lower household incomes and retard socio
      economic development. Sustainable rural development requires that nagana be
      controlled. This in turn needs considerable resources, whichever control strategy
      is adopted.

PMID- 7501370
TI  - Epidemiology and control of trypanosomosis.
AB  - Tsetse-transmitted trypanosomosis remains a major constraint to the development
      of agriculture, particularly to that of livestock production in sub-Saharan
      Africa. It is estimated that 10 million km2 of Africa are tsetse infested,
      exposing some 50 million people and 60 million cattle to the risk of
      trypanosomosis. The epidemiology of the disease is complex and is greatly
      influenced by management and farming practices. The different control strategies
      are reviewed and their comparative advantages assessed. It is concluded that
      eradication of tsetse flies, while desirable, is rarely achieved. It is perhaps
      more realistic to aim for disease suppression, with vector-control campaigns
      linked to sustainable land-use programmes. Nevertheless, progressive tsetse
      eradication remains the long-term goal.

PMID- 7501371
TI  - Epidemiology of African horsesickness: duration of viraemia in zebra (Equus
      burchelli).
AB  - The viraemic period of African horsesickness is significantly longer in
      experimentally infected zebra than in horses. The virus could be isolated 40 d
      post-infection from blood and 48 d post-infection from spleen. The introduction
      of zebra into African horsesickness-free countries should therefore be considered
      carefully, and preferably be restricted to serologically negative zebra.

PMID- 7501372
TI  - Bile enhances the infectivity of third stage larvae of Dictyocaulus filaria.

PMID- 7501373
TI  - Endoscopic orbital decompression under local anesthesia.
AB  - Orbital decompression for Graves' disease has traditionally been performed with
      the patient under general anesthesia. Endoscopic instrumentation allows for
      removal of the medial orbital wall and floor through an intranasal approach with
      local anesthetic techniques. Twelve endoscopic orbital decompressions were
      performed on awake patients with uncovered eyes so that vision could be monitored
      throughout the procedure. Simultaneous lateral decompressions were performed in
      11 cases. No intraoperative or postoperative complications occurred. Visual
      acuity remained stable or improved in all cases. Proptosis was reduced an average
      of 5.5 +/- 1.6 mm. In a comparable series of 29 endoscopic decompressions
      performed with patients under general anesthesia, proptosis was reduced an
      average of 4.8 +/- 2.0 mm. Endoscopic orbital decompression with patients under
      local anesthesia appears to be an effective technique that may provide an
      additional margin of safety in prevention of injury to the optic nerve.

PMID- 7501375
TI  - Laryngeal complications after type 1 thyroplasty.
AB  - Type I thyroplasty has become a primary surgical choice for voice restoration in
      patients with glottal incompetence. This study examines factors associated with
      laryngeal complications after type I thyroplasty. Ten laryngoscopic variables
      were analyzed from preoperative, intraoperative, and postoperative
      videolaryngoscopies of 51 patients undergoing 58 medialization procedures. Ten
      patient and operative variables were examined by medical record review. Major
      complications were defined as wound hemorrhage, airway obstruction, or prosthesis
      extrusion. Minor complications were defined as vocal fold hematoma without airway
      obstruction or prosthesis movement. The major complication rate was 8.6%, and the
      minor complication rate was 29%. No delayed hemorrhage or airway obstruction
      occurred. Prosthesis extrusion occurred in five (8.6%) patients 1 week to 5
      months after surgery. Extrusion was associated with suboptimal prosthesis
      placement in 80% of cases. Two patients retained excellent glottal closure
      despite extrusion. Vocal fold hematoma was identified in 14 (24%) cases and
      resolved within 1 week. Prosthesis movement occurred in three (5%) patients 1
      week to 6 months after surgery and resulted in poor glottal closure. All patients
      with prosthesis extrusion or movement were female. Type I thyroplasty remains a
      safe outpatient procedure with few major complications. Prosthesis extrusion was
      associated with suboptimal prosthesis placement and may or may not result in poor
      glottal closure. Minor vocal fold hematomas were relatively frequent, resolved
      rapidly, and were not associated with airway obstruction. Female patients may be
      more prone to complications because of their small laryngeal size.

PMID- 7501374
TI  - Voice failure after tracheoesophageal puncture: management with botulinum toxin.
AB  - Primary or secondary tracheoesophageal puncture with a speaking prosthesis has
      provided rehabilitation of speech in most patients after total laryngectomy.
      Persistent constrictor spasm is thought to be responsible for a small percentage
      of these patients' inability to speak with the prosthesis. Management of these
      patients has included bougienage and pharyngeal myotomy and/or pharyngeal
      neurectomy. Botulinum toxin injections of the cricopharyngeus muscle complex in
      six patients have been successfully used diagnostically and therapeutically for
      tracheoesophageal puncture failures. The assessment, technique, and results are
      discussed.

PMID- 7501376
TI  - Intractable epistaxis: transantral ligation vs. embolization: efficacy review and
      cost analysis.
AB  - After posterior nasal packing, the two most common therapies for intractable
      epistaxis are transantral ligation of the internal maxillary artery and
      percutaneous embolization of the distal internal maxillary artery. However,
      optimal management of intractable posterior epistaxis remains controversial. We
      retrospectively reviewed the charts of 21 patients treated for intractable
      epistaxis and obtained data on presentation, risk factors, treatment, success
      rates, complications, and cost. Twelve patients received percutaneous
      embolization, five underwent transantral ligation, and four required both. The
      success rates for transantral ligation and percutaneous embolization were 89% and
      94%, respectively. No mortality or serious morbidity occurred with either
      technique. A cost comparison revealed that transantral ligation was moderately
      less expensive than percutaneous embolization ($5941 vs. $6783). Although some
      authors advocate transantral ligation or percutaneous embolization as the
      procedure of choice for intractable epistaxis, a direct comparison of efficacy
      and cost reveals that they are comparable procedures with specific strengths and
      weaknesses. We present our experience and a review of the literature,
      highlighting the indications and advantages of each technique. We conclude that
      the choice of treatment modality should be based on the benefits of each
      procedure as it pertains to the specific needs of the individual patient.

PMID- 7501377
TI  - Diagnosis and treatment of unilateral cricothyroid muscle paralysis with a
      modified Isshiki type 4 thyroplasty.
AB  - Cricothyroid adduction increases tension to the vocal folds, thus increasing
      fundamental frequency and upper pitch range. We treated 10 patients with
      cricothyroid muscle dysfunction using this technique. Preoperative
      electromyographic, acoustic, and perceptual analysis was performed.
      Intraoperatively the effect of increasing tension on the fundamental, falsetto,
      and basal frequencies was measured by using a strain gauge to the adducting
      suture at several tensions and a cervical microphone connected to a pitch meter.
      Postoperative acoustic and perceptual analysis was then performed up to 18 months
      later. Analysis of pitch vs. tension curves indicates a near-linear relationship
      until very high tensions are applied. Statistically significant improvement was
      achieved in both acoustic and perceptual analysis, although some deterioration
      was noted between early and late results. Cricothyroid adduction is indicated for
      a large range of vocal fold tension problems.

PMID- 7501378
TI  - Microanalytic acoustical voice characteristics of near-total laryngectomy.
AB  - Limited acoustic data are available describing vocal characteristics of
      individuals after near-total laryngectomy. Computer-based acoustic analyses (FO,
      jitter, shimmer, signal-to-noise ratio) were performed on vowel samples produced
      by 20 speakers who underwent near-total laryngectomy. On the basis of data
      obtained, the subjects who had undergone near-total laryngectomy demonstrated (1)
      higher than normal and more variable modal fundamental frequency values for
      sustained vowels; (2) increased frequency (jitter) and amplitude (shimmer)
      perturbation; and (3) decreased spectral noise (signal-to-noise) components. In
      addition, speakers who had undergone near-total laryngectomy showed an increased
      percentage of unvoiced sound production during their vowel productions. The large
      variability and general aperiodicity of the phonatory signal during vowel
      production suggests an ineffective laryngeal valving system with overcompensation
      in attempts to generate effective voice. These findings have implications for
      designing behavioral therapy programs to improve voice quality in speakers who
      receive conservation laryngectomy procedures for treatment of laryngeal
      carcinoma.

PMID- 7501379
TI  - Clinical viral infections and temporal bone histologic studies of patients with
      AIDS.
AB  - The brain, eye, and inner ear are each protected from blood-borne infectious
      agents by a barrier that has some anatomic and functional differences. In
      patients with AIDS, opportunistic infections of the central nervous system and
      eye are frequent. Little is known about the incidence of middle and inner ear
      infections in patients with AIDS, but deafness and severe vertigo are uncommon.
      We studied 14 homosexual men with AIDS, aged 28 to 55 years, for 1 to 2 years
      until death. No patient had deafness, but one had vertigo. Adenovirus type 6 and
      cytomegalovirus were isolated from the middle ear cavity in four patients.
      Temporal bone histology demonstrated acute otitis media in four, chronic otitis
      media in two, and serous otitis media in three. Adenovirus type 6 and
      cytomegalovirus, either alone or with herpes simplex virus type 1, were isolated
      from inner fluids of three patients. Histologic inner ear findings were abnormal
      in only one patient. Viruses were isolated or histologically identified in the
      brains of four patients and in the eyes of five patients. In our patients viral
      infections were nearly as common in the inner ears as in the brain and eye,
      suggesting that protection from the blood-labyrinth barrier was similar to that
      from the other barriers. Because the inner ear viral infections were asymptomatic
      and there was an absence of pathologic damage and inflammation, we suggest that
      some viral inner ear infections in patients with AIDS are nonpathogenic and
      elicit no inflammation or that the viral infections occur terminally and elicit
      no inflammation because of immunosuppression from the AIDS.

PMID- 7501380
TI  - Immunology of delayed food allergy.
AB  - Studies here and abroad are stockpiling evidence that immunoglobulin E explains
      only a small part of food allergy. Involvement of the entire immune system is
      evident if the more prevalent delayed-type food allergy is to be explained. To
      adequately diagnose food hypersensitivity a testing technique must be used that
      identifies delayed food allergy, such as the patch test here described, along
      with a test that diagnoses immediate immunoglobulin E-mediated food allergy.

PMID- 7501381
TI  - Sinus disease in the bone marrow transplant population: incidence, risk factors,
      and complications.
AB  - BACKGROUND: Fever associated with sinus disease in the immunocompromised bone
      marrow transplant recipient requires prompt evaluation and therapy. Very little
      is known about the incidence, risk factors, and sequelae of nonsurgically treated
      sinus disease in this population. METHODS: A retrospective review of 107
      consecutive allogeneic and autologous bone marrow transplant recipients from
      August 1987 to July 1989 was performed to determine (1) the overall incidence of
      sinus disease; (2) factors that influence the development of sinus disease; and
      (3) the sequelae of sinus disease treated nonsurgically. RESULTS: Overall 33
      (31%) of 107 bone marrow transplant recipients had sinus disease defined as a
      radiographic abnormality with clinical symptoms. Eleven (10%) of 107 recipients
      had preexisting sinus disease. Sinus disease developed in 22 (21%) of 107
      recipients after bone marrow transplantation. Sinus abnormalities were
      significantly higher among allografted bone marrow transplant recipients than
      among autografted recipients (p = 0.027). The diagnosis, stage of disease,
      cytoreductive regimen, or graft-vs.-host disease were not different between
      recipients in whom sinus disease did and did not develop. There were no deaths as
      a result of sinus complications. CONCLUSIONS: Sinus disease developed in 21% of
      the studied population after bone marrow transplantation. Allogeneic recipients
      had a higher incidence of sinus disease than autologous recipients. There were no
      deaths attributed to sinus complications. All sinus disease in this bone marrow
      transplant population was treated medically. No patient required surgical
      intervention either before or after bone marrow transplantation.

PMID- 7501382
TI  - Randomized trial of the canalith repositioning procedure.
AB  - Thirty-six subjects with confirmed, unilateral benign paroxysmal positioning
      vertigo of at least 2 months' duration were randomly assigned to one of two
      treatment groups. After complete informational counseling and explanation of the
      posttreatment instructions, subjects were randomly assigned to receive either
      Epley's canalith repositioning procedure or a placebo maneuver. All subjects
      completed a daily diary for 1 month to document any dizzy spells and their
      adherence to the posttreatment instructions. Follow-up Dix-Hallpike testing was
      performed after 1 month by an audiologist who was blinded to the patient's
      treatment group status. Analysis of Dix-Hallpike results confirmed that those who
      received the canalith repositioning procedure had significantly more negative
      responses (88.9%) than did those in the placebo group (26.7%).

PMID- 7501383
TI  - Radioallergosorbent microscreen and total immunoglobulin E in allergic fungal
      sinusitis.
AB  - One of the commonly held concepts regarding allergic fungal sinusitis is that
      patients with this disorder also demonstrate allergy to other inhalants. However,
      few published investigations have confirmed this. In this study serum from 16
      consecutive patients with histologically proven allergic fungal sinusitis was
      tested with a seasonal and a perennial radioallergosorbent microscreen disk. The
      seasonal radioallergosorbent microscreen combines on one disk antigens for two
      grasses, two weeds, and two trees, and the perennial disk contains Alternaria and
      dust mite antigens. Total immunoglobulin E was also determined for each sample.
      Fifteen of the 16 samples demonstrated a radioallergosorbent class II or greater
      response to both. The total immunoglobulin E level was greater than 100 units/ml
      in 14 samples (> 1000 in 4 cases) and 97 units/ml in another. This study
      addresses the presence of inhalant allergy in patients with allergic fungal
      sinusitis previously described in case reports. The results support the concept
      that allergic fungal sinusitis is a true allergic (rather than infectious)
      disease.

PMID- 7501384
TI  - Role of allergy in nasal polyposis: a review.
AB  - We propose a multivariate theory for the pathogenesis of nasal polyps. Turbulent
      flow of air in the lateral wall of the nose or viral-bacterial-host interactions
      produce an inflammatory change in the mucosa of the lateral wall of the nose.
      Ulceration and prolapse of the submucosa with reepithelialization and new gland
      formation may then follow. The structural cells of the nasal polyp, including
      epithelial cells and fibroblasts, have the ability to produce messenger RNA for
      granulocyte-monocyte colony-stimulating factor and other cytokines. Stimulation
      of such an effector capability by structural cell-derived cytokines would
      undoubtedly represent a major amplification pathway of the inflammatory response
      in nasal polyps. Allergy may be one mechanism for the development of this cascade
      of events. This microenvironmental structural inflammatory response in the nasal
      polyp, in turn, can affect the bioelectric integrity of the Na+ and Cl- channels
      at the luminal surface of the respiratory epithelial cell. The change in the Na+
      absorption, which has been demonstrated in our studies, may result in an
      increased movement of water into the cell and into the interstitial fluid. The
      resultant edema can lead to growth and enlargement of the nasal polyp. Finally,
      the rapid recurrence of nasal polyps despite adequate surgery may reflect some
      intrinsic phenotypic characteristic of nasal epithelial cells in the lateral wall
      of the nose, which is likely to be under genetic control.

PMID- 7501386
TI  - Forehead flap in nasal reconstruction.
AB  - We establish criteria for anesthetic forehead flap reconstructions and evaluate
      the effect of mathematical models and computer simulation of the operation in
      preoperative and perioperative planning. We study a case series of 13 patients in
      an academic tertiary referral medical center. Most patients had nasal defects
      after Mohs' surgery for tumor ablation. Patients were followed up for 2 years
      after reconstructive surgery. Three patients underwent midline forehead flap
      nasal reconstructions, and 10 patients underwent paramedian forehead flap nasal
      reconstructions. We used patient satisfaction and physician evaluation of
      aesthetic form and function restoration as the main outcome measures. There were
      no major complications. Minor complications included short-term pincushioning in
      all patients, scar contracture that resolved after 8 months in one patient, and
      forehead necrosis after primary closure of the upper forehead in one patient.
      Computer simulation correlated two-dimension flap design to the transposition
      process. We conclude that the forehead flap is the optimal reconstructive
      modality for resurfacing large nasal defects. The paramedian forehead flap is
      superior to the midline forehead flap for nasal reconstruction, especially for
      distal tip reconstructions. Mathematical models and computer simulation of the
      reconstructive procedure that relate the two-dimensional flap design to the
      transposition process reveal subtle geometric relationships of the flap
      transposition that facilitate the design of the optimal flap for reconstruction.

PMID- 7501385
TI  - Attitudes, knowledge, and practices of otolaryngologists treating patients
      infected with HIV.
AB  - The AIDS epidemic has become one of the most important public health problems of
      this century. As the prevalence of HIV infection continues to rise, health care
      practitioners in all geographic regions can expect greater clinical exposure to
      patients infected with HIV. We conducted an anonymous survey of all practicing
      otolaryngologists in Ohio and California to investigate regional differences in
      attitudes, knowledge, and practices regarding the care of patients infected with
      HIV. We also examined the data with respect to year of completion of residency
      training to identify differences in attitudes or practices among
      otolaryngologists who trained in the era of AIDS (post-1982 graduates) in
      comparison with their predecessors (pre-1982 graduates). In comparison with Ohio
      otolaryngologists, California otolaryngologists reported more frequent clinical
      encounters with HIV-infected patients and displayed significantly better
      knowledge regarding the otolaryngologic aspects of HIV infection. Californians
      were more likely to support the right of an HIV-infected physician to maintain an
      unrestricted practice and would be less likely to disclose their HIV status to
      their patients and hospital if they were to become infected with HIV. Post-1982
      graduates had more frequent encounters with HIV-infected patients than did pre
      1982 graduates and demonstrated a better fund of knowledge. Although Californians
      were more likely than Ohioans to routinely double glove in surgery, the overall
      double gloving rate was low at 21%. Californians were no more likely than Ohioans
      to routinely use protective eyewear, water-impervious gowns, or indirect
      instrument-passing techniques in surgery. No differences were observed in
      prevalence of protective surgical precautions between pre-1982 and post-1982
      graduates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501387
TI  - Consumption of a high-galactose diet induces diabetic-like changes in the inner
      ear.
AB  - Diabetes mellitus is a disease that affects multiple organ systems. In our
      laboratory it has been shown that there is a significant loss of outer hair cells
      in genetically diabetic rats. Galactosemia can also produce diabetic-like
      changes. This study was performed to demonstrate whether these changes also occur
      in the cochlea. Three groups of Sprague-Dawley rats were used and fed either a
      control diet, a 50% galactose diet, or a 50% galactose diet with the addition of
      an aldose reductase inhibitor. After 6 months the animals were killed, and the
      cochleas were removed, fixed, and stained. Diabetes-induced damage was assessed
      by counting the hair cells and calculating the neuroganglion cell density. The
      histopathologic changes induced by galactose were manifested as outer hair cell
      loss and a decrease in neuroganglion cell density. Control animals had the least
      amount of hair cell loss and the greatest neuroganglion cell density of all three
      groups. Galactose-only animals demonstrated the most pronounced changes in both
      hair cell loss and neuroganglion cell degeneration; however, only changes of
      neuroganglion cell density in the basal turn were significant. The addition of an
      aldose reductase inhibitor provided inconclusive results in both hair cell
      determination and neuroganglion cell density; however, generally the inhibitor
      partially prevented the damage produced by galactose. These results suggest that
      a high-galactose diet can induce diabetic-like changes in the cochlea.

PMID- 7501388
TI  - Neurotransmitters for the canine inferior pharyngeal constrictor muscle.
AB  - The inferior pharyngeal constrictor muscle plays an important role at the
      pharyngeal phase of deglutition and is anatomically composed of the
      thyropharyngeal muscle and cricopharyngeal muscle. In this study we investigated
      the distribution pattern of neuropeptidergic and catecholaminergic nerve fibers
      in the thyropharyngeal muscle and cricopharyngeal muscle of seven puppies by
      immunohistochemistry. Some of the calcitonin gene-related peptide-, substance P-,
      vasoactive intestinal polypeptide-, and tyrosine hydroxylase-immunoreactive nerve
      fibers were found to lie parallel to the muscle fibers in both the
      thyropharyngeal muscle and cricopharyngeal muscle. Nerve fibers with
      immunoreactivity to all substances examined were found to be associated with
      blood vessels in both the thyropharyngeal muscle and cricopharyngeal muscle, and
      the number of calcitonin gene-related peptide, neuropeptide Y, and tyrosine
      hydroxylase nerve fibers was higher than the number of substance P, vasoactive
      intestinal polypeptide, and galanin nerve fibers. Motor end plate-like structures
      with calcitonin gene-related peptide immunoreactivity were found in both the
      thyropharyngeal muscle and cricopharyngeal muscle. These structures in the
      cricopharyngeal muscle were clearly less than those in the thyropharyngeal
      muscle. Some clusters of neurons were detected only in the cricopharyngeal muscle
      of all dogs examined. Substance P-, vasoactive intestinal polypeptide-, galanin-,
      and neuropeptide Y-immunoreactive neurons were found in this ganglion, and the
      vasoactive intestinal polypeptide-immunoreactive neurons were the most abundant.
      Abundant calcitonin gene-related peptide- and vasoactive intestinal polypeptide
      immunoreactive nerve fibers, and some substance P- and galanin-immunoreactive
      nerve fibers were distributed in the ganglion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501389
TI  - An investigation of acute facial paralysis in animals induced by exposure of the
      tympanic membrane to cold air.
AB  - The goal of this investigation was to test the hypothesis that tympanic membrane
      exposure to cold air is a cause of acute facial palsy. A series of acute invasive
      experiments and a series of chronic noninvasive experiments were conducted in
      both cats and dogs. In the acute studies, stimulation was applied intracranially
      to the facial nerve root through a stereotaxically placed microelectrode and
      recordings of compound action potentials obtained extracranially from the facial
      nerve. Nerve conduction was monitored continuously during the application of cold
      air to the tympanic membrane. Nerve conduction disturbances were observed in all
      animals tested (8), and reduction in compound action potential amplitude ranged
      from 33% to 96%. Histologic analysis of the intratemporal portion of the facial
      nerve was performed in the animal exhibiting the greatest block in conduction,
      representative of a near-total paralysis. Axon swelling, demyelinization, and
      degeneration (Bungner's bands) without inflammation were apparent along the
      entire tympanic membrane segment. Interstitial swelling of nerve endoneurium was
      also present at the second genu and vertical segment. In the chronic studies,
      animals were exposed to cold air and monitored daily for facial paralysis after
      recovery from anesthesia. None of the animals demonstrated any detectable
      behavioral facial paralysis.

PMID- 7501390
TI  - Intranasal papillary endothelial hyperplasia.

PMID- 7501391
TI  - Inverted papilloma isolated to the sphenoid sinus.

PMID- 7501392
TI  - Plexiform neurofibroma of the retropharyngeal space: a case report.

PMID- 7501393
TI  - Allergic reaction to solid silicone implant in medial thyroplasty.

PMID- 7501394
TI  - Partial DiGeorge anomaly presenting as an enlarging third pharyngeal pouch cyst.

PMID- 7501395
TI  - Botulinum toxin injection for postlaryngectomy tracheoesophageal speech failure.

PMID- 7501396
TI  - Cutaneous T-cell lymphoma presenting as a large scalp mass.

PMID- 7501397
TI  - Inflammatory pseudotumor of the tonsil.

PMID- 7501398
TI  - Oculostapedial synkinesis.
AB  - A 51-year-old woman with persistent oculostapedial synkinesis after successful
      microvascular surgical decompression of the facial nerve in the cerebellopontine
      angle is presented. Auditory symptoms are common in patients with hemifacial
      spasm manifested by a low-pitch rumbling noise, ear fullness or stuffiness,
      subjective reduction of hearing acuity, and as described in this case, ear
      tightness and "drumming." Ephaptic neural transmission is the proposed cause of
      hemifacial spasm. The exacerbation of auditory symptoms with voluntary blinking
      and eye closure can be explained by ephaptic transmission and/or aberrant
      regeneration. Should the aggravating and annoying symptoms of stapedial muscle
      dysfunction persist in the face of successful treatment of hemifacial spasm,
      transmeatal division of the stapedial tendon provides immediate relief.

PMID- 7501399
TI  - Laryngotracheal stenosis in thoracolaryngopelvic dysplasia: Barnes syndrome.

PMID- 7501400
TI  - Combined chemotherapy and radiation in the treatment of a large nasal cavity
      tumor: a case report.

PMID- 7501401
TI  - Nasal manifestations of Crohn's disease.

PMID- 7501402
TI  - Intraoral benign mesenchymomas.

PMID- 7501403
TI  - Metastatic melanoma to the pharynx and trachea.

PMID- 7501406
TI  - An unusual first branchial cleft defect.

PMID- 7501404
TI  - Spontaneous cerebrospinal fluid rhinorrhea through the cribriform plate fistula
      cured by endonasal surgery: transseptal submucoperiosteal obliteration of the
      olfactory cleft.

PMID- 7501407
TI  - Glomangioma of the auricle.

PMID- 7501405
TI  - Facial paralysis and inflammatory pseudotumor of the facial nerve in a child.

PMID- 7501408
TI  - Blues' reimbursement, managed competition, and House Bill 630.

PMID- 7501409
TI  - Reevaluating the state's cost containment council.

PMID- 7501410
TI  - Taming the CAT Fund: two decades of challenges.
AB  - The CAT Fund on September 30 announced a 68 percent emergency surcharge to settle
      approximately $108 million in unpaid claims. Physicians across the state are
      asking how--and why--this happened. The Society's general counsel takes an
      historical look at the fund and offers a realistic solution to curtail similar
      "surprises" in the future.

PMID- 7501411
TI  - "Fam-Med": an Internet list for small practices.
AB  - A small-town family physician, fearing that colleagues in solo and small
      practices might be ignored by organizations developing new computer applications
      in medicine, created Fam-Med, an Internet computer information clearinghouse for
      doctors who practice family medicine. This installment of our series on computers
      and medicine describes Fam-Med and how to reach it.

PMID- 7501412
TI  - Becoming an advocate for the elderly.
AB  - The Pennsylvania Department of Aging reports that as many as one in 20 older
      adults may be victims of abuse. In this article, John M. Prendergast, MD, MPH,
      medical director of the Center for Aging at Mercy Hospital, Pittsburgh, discusses
      what he considers to be the most prevalent form of abuse--passive neglect. He
      considers it a problem about which all physicians should be better educated.

PMID- 7501413
TI  - KePRO prepares for new national cooperative project.

PMID- 7501415
TI  - Pennsylvanians for merit selection.

PMID- 7501414
TI  - Telemedicine and the payment system.
AB  - Free medical phone service has become a professional courtesy, but recent changes
      in the practice environment should prompt a reexamination of this free service as
      perhaps an anachronism which is getting in the way of progress.

PMID- 7501416
TI  - Patient impatience can cost your practice business.

PMID- 7501417
TI  - Why are we here?

PMID- 7501418
TI  - Retiring from medicine: the grief process.

PMID- 7501419
TI  - Immunoregulation in human lymphatic filariasis: the role of interleukin 10.
AB  - In humans with lymphatic filariasis microfilaremia is associated with a parasite
      antigen-specific hyporesponsiveness when assessed by cell proliferation and
      secretion of interleukin-2 and interferon-gamma. Hyporesponsiveness in these
      individuals is not only parasite antigen-specific but appears to be limited to
      Th1-type responses. Th2 mediated responses such as IL-5 secretion and IgE
      antibody production to parasite antigens are generally strong and usually no
      different than those seen in immunologically more reactive amicrofilaremic
      individuals with chronic lymphatic pathology. The mechanisms by which Th1
      responses are inhibited have not yet been elucidated, but some studies suggest
      that down-regulatory cytokines such as IL-10 may be involved in this process.
      Mononuclear cells from microfilaremic individuals have been found to secrete
      greater quantities of IL-10 spontaneously and in response to parasite antigens.
      In this review, mechanisms by which IL-10 may be induced by the parasite and the
      mode by which IL-10 may regulate parasite antigen-specific Th1 responses in these
      individuals are discussed.

PMID- 7501420
TI  - Temporal changes in the humoral immune response of cattle during experimental
      infections with Onchocerca lienalis.
AB  - In order to gain insights into the immune response in onchocerciasis during early
      infection, laboratory-reared calves were infected with 1000 Onchocerca lienalis
      infective larvae and examined serologically over a period of 508 days. Levels of
      serum antibodies measured by ELISA against adult worm extract revealed a
      multiphasic response, characterized by a broadly similar profile of peaks in
      individual animals arising at 15-30, 79 and > 266 days after infection. Timings
      of these changes in responsiveness closely mirrored parasite development,
      coinciding with larval moults and with the onset of a patent infection. The
      levels of individual antibody isotypes directed against parasite antigens was
      strongly skewed. The dominant response was of IgG1, although limited reactivities
      were also found for IgG2 and IgM: No parasite-specific IgA antibodies were
      detected. Immunoblots of adult worms extracts revealed a pattern of antigen
      recognition over time that matched the results obtained by ELISA. Again, the IgG1
      response was strongest, although certain IgG2 and IgM specificities were well
      represented. In general, there was a steady increase in the number of individual
      antigens recognized as the infection progressed, with a striking expansion of
      antibody specificities from day 79 following the fourth larval moult. Antibodies
      to a 16kDa component were a prominent feature of the response following
      development of a patent infection. These data reveal the strong influence of
      parasite biology on the development of the immune response in onchocerciasis.

PMID- 7501421
TI  - Reactive nitrogen intermediates implicated in the inhibition of Encephalitozoon
      cuniculi (phylum microspora) replication in murine peritoneal macrophages.
AB  - Encephalitozoon cuniculi (phylum microspora) is a protozoan parasite that can
      replicate within parasitophorous vacuoles in macrophages. Thioglycollate-elicited
      BALB/c peritoneal macrophages treated with murine recombinant interferon-gamma
      (rIFN-gamma; 100 7/ml) in combination with lipopolysaccharide (LPS; 10 ng/ml) for
      24 h killed E. cuniculi as determined by significant reductions in the number of
      parasites and percent of infected macrophages 48 h later compared with cultures
      treated with medium only. Treatment of the elicited macrophages with murine rIFN
      gamma (10 u/ml or 100 u/ml) only, resulted in microbistatic activity.
      Significantly higher levels of nitrite (NO2) were detected in supernatants from
      macrophage cultures treated with rIFN-gamma (10 u/ml or 100 u/ml) which induced
      microbistatic macrophage activity as well as from macrophage cultures treated
      with LPS + rIFN- when compared with levels of nitrite detected in supernatants of
      infected macrophages treated with medium only. Addition of the L-arginine
      analogue, N3 monomethyl-L-arginine (NMMA) at concentrations of 50, 100 or 250 uM
      significantly inhibited nitrite synthesis and prevented microsporidia killing.
      Addition of exogenous L-arginine at concentrations of 5 mM or 10 mM reversed the
      NMMA-induced inhibition of parasite killing. These results indicate that reactive
      nitrogen intermediates contribute to the killing of E. cuniculi by LPS + rIFN
      gamma-activated murine peritoneal macrophages in vitro.

PMID- 7501422
TI  - Cytokine profiles for human V gamma 9+ T cells stimulated by Plasmodium
      falciparum.
AB  - V gamma 9+ T cells from malaria non-exposed donors make proliferative responses
      to Plasmodium falciparum on in vitro stimulation. V gamma 9+ cells are strongly
      activated by components of the schizont stage of the parasite and by antigens
      released into the culture upon schizogony, while CD4+V gamma 9- cells are
      stimulated by the earlier stages of the parasite. Using reverse transcriptase
      polymerase chain reaction (RT-PCR) we determined mRNA expression for 14 cytokines
      in highly purified V gamma 9+ cells enriched by positive selection after in vitro
      stimulation with P. falciparum schizont antigens. Interferon-gamma (IFN-gamma)
      and Tumor Necrosis Factor-alpha (TNF-alpha) were detected in all samples tested.
      The majority of samples also expressed TNF-beta, transforming growth factor-beta
      (TGF-beta) and Interleukin-8 (IL-8). Only occasional samples expressed IL-2, IL-5
      and IL-10. Using the ELISPOT assay we found that a large fraction of the reactive
      V gamma 9+ cells produced IFN-gamma and that gamma delta T cells are the major
      producers of IFN-gamma in cultures stimulated with schizont antigens. The
      majority of V gamma 9+ cells in these cultures also express the membrane-bound
      form of TNF-alpha. Expression of these cytokines speaks for a cytolytic and/or
      inflammatory role of gamma delta cells in the response to malaria in non-exposed
      individuals.

PMID- 7501423
TI  - The combined epidermal growth factor-like modules of Plasmodium yoelii Merozoite
      Surface Protein-1 are required for a protective immune response to the parasite.
AB  - We have reported previously that immunization with a bacterial recombinant
      protein containing the two epidermal growth factor (EGF)-like modules of
      Plasmodium yoelii Merozoite Surface Protein-1 (MSP-1) protected mice against
      challenge with this malaria parasite. Bacterial plasmids containing sequences
      coding for the individual modules fused to glutathione S-transferase (GST) have
      now been made. The fusion protein containing the combined EGF-like modules was
      recognized by anti-parasite antibodies and was immunogenic, producing high titre
      anti-parasite and anti-GST antibodies. In contrast, fusion proteins containing
      the two individual EGF-like modules reacted poorly with the natural antibodies
      and their proteins, as well as a simple mixture of them, induced low levels of
      anti-parasite antibodies despite producing high levels of anti-GST antibody.
      Antibodies raised to the recombinant proteins recognized the 230 kDa MSP-1.
      Groups of mice immunized with the different recombinant proteins were challenged
      with parasites: protection was observed in the group which had received the
      recombinant protein containing both modules but not in those groups immunized
      with the individual modules, either alone or as a mixture. These results suggest
      that there are important structural determinants formed by the two modules
      together, which are not present in either of the individual domains alone, and
      which are responsible for the immunogenicity of the protein or are the target of
      protective antibodies.

PMID- 7501425
TI  - A pilot safety and immunogenicity study of the malaria vaccine SPf66 in Gambian
      infants.
AB  - A pilot safety and immunogenicity trial of the malaria vaccine SPf66 has been
      undertaken in 150 Gambian infants. No significant systemic side effects were
      recorded but modest local reactions were seen after the administration of a third
      1.0 mg dose. SPf66 produced in Colombia was more immunogenic than SPf66 produced
      in the USA and a 1.0 mg dose of each vaccine gave higher antibody levels than a
      0.5 mg dose. However, antibody levels fell rapidly after administration of the
      third dose of vaccine and showed little change over the following malaria
      transmission season. The incidence of clinical malaria was higher among children
      who received SPf66 than among children who received inactivated polio vaccine,
      the effect being most marked among children who received 1.0 mg Colombian SPf66.
      As the trial was not designed to measure the effect of SPf66 on morbidity from
      malaria, the significance of this finding is uncertain.

PMID- 7501424
TI  - Comparative phenotypic analysis of lymph node cells in mice after infection or
      vaccination with normal or ultraviolet-attenuated cercariae of Schistosoma
      japonicum or S. mansoni.
AB  - Mice were infected with 200 untreated or vaccinated with 500 ultraviolet
      attenuated cercariae of either Schistosoma japonicum or S. mansoni. For three
      weeks, cell numbers in axillary and mediastinal lymphnodes were counted and cell
      populations typed by cytofluorometry. In the axillary lymphnodes, numbers of B
      cells and CD3+CD4+ T-cells but not CD3+CD8+ T-cells increased. Following
      vaccination with either species, parasite migration was apparently delayed in the
      skin and interrupted at the lungs, the lymphnodes gained weight, and cell numbers
      of axillary lymph nodes increased more than after infection. In mediastinal
      lymphnodes, only immunization with S. japonicum but not S. mansoni cercariae led
      to an increase of CD3+CD4+ T-cells. Following infection, both schistosome species
      induced higher CD3+CD4+, but not CD3+CD8+ T-cells in mediastinal nodes, and the
      peak was earlier with S. japonicum (about seven days after infection) than with
      S. mansoni (about 10 days). In analogy to T-cell observations by others using a
      gamma-attenuated cercarial vaccine in S. mansoni, the present results suggest
      that CD3+CD4+ cells also play a role in the ultraviolet-attenuated vaccine
      against S. japonicum.

PMID- 7501426
TI  - [Status of pathophysiologic research in the field of oncology].
AB  - The state of cancer researches is considered from two points of view: 1) study of
      the properties and specific features of a malignant cell and 2) establishment of
      the important role of regulatory systems in the tumor-afflicted body in terms of
      their performance at its different integration levels. Preference is given to the
      second approach as the most promising tool in developing basic and applied tasks
      of oncology. It is the second approach which will assist in solving issues
      associated with neoplasmic prevention and therapy.

PMID- 7501427
TI  - [Change in the functional activity of the blood complement system after
      administration of adrenaline to animals].
AB  - Epinephrine given to non-inbred male albino rats in a pharmacological dose of 1
      mg/kg was studied for effects on their serum complement. Following 5 min of its
      administration, the complement activity both of blood overall and individual
      parameters reduced by 0.4-0.7 log2 as compared with the baseline, 20 minutes
      after it significantly increased up to 0.5 log 2 as compared with the baseline
      titer, and returned to the baseline level 2 hours later. Following 24 hours of
      epinephrine administration, complement activity again increased, by reaching its
      peak on days 2 and 3 of the experiment and accounting for 1.5-2.0 log2 as
      compared with the baseline titer. The alpha-adrenoblocker tropaphen did not
      affect the epinephrine-induced suppression of complement activity 5 minutes after
      its use and enhanced the mediated effect of the complement activity growth
      associated hormone on days 2 and 3 of the experiment. Blockade with the beta
      adrenoreceptor inderal virtually failed to affect the complement-mediated action
      on epinephrine on days 2 and 3 of its use.

PMID- 7501429
TI  - [Effect of soluble streptocide on the function of type III glucocorticoid
      receptors in rat liver cytosol].
AB  - The effects of soluble streptocidum on the function of Type III glucocorticoid
      receptors in the hepatic cytosol were examined in Wistar rats weighing 180-200 g.
      The Scatchard Lainuiver-Berk established that soluble streptocidum resulted in a
      concentration-dependent increase in the number of Type III glucocorticoid
      receptor binding sites. At the same time the measured constant of interaction of
      labelled corticosterone with Type III glucocorticoid receptors and the
      dissociation constant of these complexes slightly changed with streptocidum.
      Soluble streptocidum-induced stimulation of the function of Type III
      glucocorticoid receptors was effected via the non-competitive type. Whether Type
      III glucocorticoid receptors directly involve in the mechanism of the
      antiphlogogenic effect of soluble streptocidum in aseptic inflammation is
      discussed in the paper.

PMID- 7501428
TI  - [Activity of the complement system in blood serum of dogs after treatment of
      acute necrotic pancreatitis with boiled pancreatic juice].
AB  - The investigations were conducted on 14 dogs. To assess the blood serum
      complement system, the erythrocyte lytic rate of a rabbit (RE) and a sheep (SE),
      the hemolytic capacity of the complement system against rabbit (RH) and sheep
      (SH) was measured. In acute necrotic pancreatitis, no changes in SE and SH were
      revealed either in the control and experimental animals. RH was decreased both in
      the control and experimental animals. Lower RE was found only in the controls
      untreated with boiled pancreatic juice. It can be suggested that in the controls
      the decrease in the parameter RE that characterized the activity of the
      complement system is associated with the emergence of complement inhibitors,
      which did not take place when the boiled juice was given. Preventing the
      complement inhibitors from forming, pancreatic juice is likely to be able to
      diminish the body's endogenous intoxication which is a cause of death in acute
      necrotic pancreatitis. This may be suggested by the higher survival of the
      animals and lower relative extent of pancreatic acinar tissue necrosis after
      boiled pancreatic juice treatment of acute necrotic pancreatitis.

PMID- 7501430
TI  - [Disorders of hemostasis in orthotopic liver transplantation in an experiment].
AB  - The study was undertaken to examine blood coagulative parameters in experimental
      orthotopic liver grafting. Plasma hemostatic parameters were studied in animals
      undergone successful and unsuccessful surgery. The preservation of a graft,
      anesthetization, and blood-substitute therapy were found to substantially affect
      the severity of hemostatic disorders. The liver-free period was characterized by
      changes in the fibrinolytic system and the activity of a plasma coagulation, by
      enhanced hypocoagulation, and thrombocytopenia. The findings suggest that timely
      correction of blood coagulative disorders is highly essential in orthotopic liver
      grafting. Prevention and prompt correction of hypocoagulation and
      thrombocytopenia are the most urgent.

PMID- 7501431
TI  - [The right heart ventricle during hemodynamic overload of the left ventricle].
AB  - Two types of hemodynamic overload were simulated in rabbits: renovascular
      arterial hypertension by the Goldblatt method and the half coarctation of the
      ascending aorta versus the baseline diameter. The functional indices and
      ultrastructure of the left and right ventricles were studied in different periods
      of these processes. If the left ventricle is hemodynamically overloaded, the
      right one immediately takes part in the process and then largely governs the
      performance dynamics of the whole heart.

PMID- 7501432
TI  - [Assessing the basic stages of the phagocytic process: current approaches to and
      prospects for research development].
AB  - The paper combines dedications to the marked event of Russian biology and
      medicine, I. I. Mechnikov's 150th birthday, and to the development of one of the
      most important problems of modern experimental medicine, the application of
      advances made in the study of phagocytosis to clinical practice. Based on the
      data available in the literature and their own findings, approaches to a stepwise
      assessment of phagocytosis is substantiated. A special attention is given to the
      discussion of the clinically available techniques which adequately evaluate
      phagocytic adhesion, degranulation processes, oxygen metabolic activation giving
      rise to active forms of oxygen, nitrogen, the killing and decomposition of
      phagocytotic objects. The material is presented by aiming at the tasks of
      clinical medicine to diagnose the major phagocytotic disorders within the general
      examination of immunity functions.

PMID- 7501433
TI  - [Role of endogenous biologically active substances in the regulation of pulmonary
      circulation in patients with hypervolemic congenital heart defects].

PMID- 7501434
TI  - [Comparative study of the effect of carbon dioxide on the generation of active
      forms of oxygen by leukocytes in health and in bronchial asthma].
AB  - The study was conducted by using leukocytes isolated from 74 apparently healthy
      donors and 60 patients with bronchial asthma. The generation of active oxygen
      forms was determined by luminolo- and lucigenin-dependent chemiluminescence
      techniques and NTC-reaction. The findings suggest that at the tension close to
      the blood tension of 37.5 mm Hg and the high tension of 146 mm Hg is a powerful
      natural inhibitor of leukocytic generation of active oxygen forms. At an
      exacerbation, the inhibitory effect of carbon dioxide on the leukocytic
      generation of active oxygen forms decreased in most (70%) patients with bronchial
      asthma, which potentiates the free radical mechanism of development of bronchial
      asthma. It may be held that the literature-described use of carbon dioxide for
      the treatment of bronchial asthma is justifiable only in a lower proportion of
      patients who have preserved a high sensitivity to the inhibitory effect of carbon
      dioxide on the generation of active oxygen forms.

PMID- 7501435
TI  - [Biochemical composition of a surfactant and its free radical processes in
      hyperbaric oxygenation and in the post-hyperoxic period].
AB  - Monitoring was made to examine the lungs. With this mode of hyperbaric
      oxygenation (0.3 MPa for 5 hours), rats developed mild oxygen intoxication which
      alleviated on day 3 and ceased on day 7 after its exposure. At the same time
      there were profound changes in the surfactant levels of protein, phospholipids,
      and cholesterol, which became normal on day 7 of postexposure. Chemiluminescence
      analysis and measurements of lipid peroxidation (PLO) products indicated that PLO
      rates in the surfactant decreased during hyperbaric oxygenation and remained at
      low levels within 24 hours of postexposure, whose cause might be activated by the
      antioxidative systems, as considered by the authors. However, on day 3 PLO
      enhances and on day 7 a new level of free-radical processes established, which
      was characterized by higher concentrations of free radicals and enhanced the
      activity of the antiradical systems.

PMID- 7501436
TI  - [Role of vasopressin and aldosterone in the mechanism of osmoregulating
      reaction].
AB  - Possible mechanisms responsible for a natriuretic response to NaCl hypertonic
      solution (515 mmol/l) digestively administered were studied in chronic
      experiments on Wistar and Brattleboro rats with continuously implanted urinary
      bladder catheters. The administration of the solution resulted in rapid
      antidiuresis and marked natriuresis though the plasma levels of N+ remained
      unchanged throughout the experiment. Natriuresis did not differ in the
      Brattleboro and Wistar rats. The time course of blood aldosterone was examined in
      experiments on Wistar rats. There was its double statistically significant
      decrease. It is suggested that in addition to secretion of hypophyseal
      neuropeptides there are additional reflex mechanisms that modulate natriuresis in
      osmotic irritation of the liver and that these mechanisms may trigger a decrease
      in plasma aldosterone levels.

PMID- 7501437
TI  - [Phospholipid spectrum in target organs in chronic stress].
AB  - The phospholipid composition of the viscera, such as the heart, liver, the fundal
      part of the stomach, arterial wall and the truncal part of the brain, was studied
      in rats exposed to chronic stress. The changes in the visceral phospholipid
      spectrum during chronic stress were found to be phasic, which appeared as
      significant increases in parameters under study within the first fortnight and
      their drastic drop at month 2 of stress. The time course of changes occurring in
      the phospholipid spectrum was held to be associated with adaptive and maladaptive
      phases of chronic stress. Unlike the viscera, the brain and erythrocytes showed
      no substantial changes in the major phospholipid fractions during chronic stress.
      The findings are regarded as evidence for the change-over of carbohydrate
      oxidation to lipid oxidation in the viscera during chronic stress, but not in the
      brain and erythrocytes.

PMID- 7501438
TI  - Restriction endonuclease BsoFI is sensitive to the 5'-methylation of
      deoxycytidines in its recognition sequence.
AB  - The isoschizomeric restriction endonucleases Fnu4HI and BsoFI cleave DNA at 5'
      GCdecreasesNGC-3' sequences. Fnu4HI has been shown to be inhibited by 5'-CG
      3'methylation in the sequences 5'-GmCGGC-3' or 5'-GCGGmCG-3'. We have now
      investigated the methylation sensitivity of BsoFI by testing its activity on
      plasmid DNA 5'-CG-3' methylated with the M.SssI DNA methyltransferase or on
      synthetic (CGG)n repetitive oligodeoxyribonucleotides which have been partly or
      completely C methylated. The data demonstrate that BsoFI cannot cleave at its
      recognition sequence when it is completely 5'-CG-3' methylated. These enzymes
      have proven to be useful in analyses of the methylation status in (CGG)n repeats
      of the human genome.

PMID- 7501440
TI  - Nonsense suppressor and antisuppressor mutations at the 1409-1491 base pair in
      the decoding region of Escherichia coli 16S rRNA.
AB  - Using a genetic selection for suppressors of a UGA nonsense mutation in trpA, we
      have isolated a G to A transition mutation at position 1491 in the decoding
      region of 16S rRNA. This suppressor displayed no codon specificity, suppressing
      UGA, UAG and UAA nonsense mutations and +1 and -1 frameshift mutations in lacZ.
      Subsequent examination of a series of mutations at G1491 and its base-pairing
      partner C1409 revealed various effects on nonsense suppression and frameshifting.
      Mutations that prevented Watson-Crick base pairing between these residues were
      observed to increase misreading and frameshifting. However, double mutations that
      retained pairing potential produced an antisuppressor or hyperaccurate phenotype.
      Previous studies of antibiotic resistance mutations and antibiotic and tRNA
      footprints have placed G1491 and C1409 near the site of codon-anticodon pairing.
      The results of this study demonstrate that the nature of the interaction of these
      two residues influences the fidelity of tRNA selection.

PMID- 7501439
TI  - The chromo superfamily: new members, duplication of the chromo domain and
      possible role in delivering transcription regulators to chromatin.
AB  - Using computer methods for detecting conserved amino acid sequence motifs, we
      show that the chromatin organization modifier (chromo) domain that has been
      previously identified in several proteins involved in transcription down
      regulation is present in a much larger group of (putative) chromatin-binding
      proteins, some of which are positive rather than negative regulators of
      transcription. The most interesting new members of the chromo superfamily are
      Drosophila male-specific lethal (MSL-3) protein involved in the X chromosome gene
      dosage compensation in the males and human retinoblastoma-binding protein RBP-1.
      We show that the chromo domain is duplicated in several chromatin-binding
      proteins and use this observation to interpret recent results on chromatin
      binding obtained with chimeric chromo domain-containing proteins. We hypothesize
      that the chromo domain may be a vehicle that delivers both positive and negative
      transcription regulators to the sites of their action on chromatin.

PMID- 7501441
TI  - Binding of phosphorothioate oligodeoxynucleotides to basic fibroblast growth
      factor, recombinant soluble CD4, laminin and fibronectin is P-chirality
      independent.
AB  - Antisense oligodeoxynucleotides can selectively inhibit the expression of
      individual genes and thus have potential applications in anticancer and antiviral
      therapy. A critical prerequisite to their use as therapeutic agents is the
      understanding of their non-specific interactions with biological structures, e.g.
      proteins. In this study we examined the interactions of P-chiral phosphorothioate
      oligodeoxynucleotides with several proteins. The Rp- and Sp- diastereomers, and
      racemic machine-made mixtures, or M-oligodeoxynucleotides were used independently
      as competitors of the binding of a probe, phosphodiester oligodeoxynucleotide
      bearing a 5' alkylating moiety, to rsCD4, bFGF and laminin. These
      oligodeoxynucleotides were also used as competitors of the binding of a non
      alkylating probe M-phosphorothioate oligodeoxynucleotide, 5'-32P-SdT18 to
      fibronectin. The average values of and quantitative estimates for the IC50 of
      competition and the constant of competition (Kc) of Rp-, Sp- and M-stereoisomers
      of several homo- and heteropolymer oligodeoxynucleotides were determined and
      compared. Surprisingly, in the proteins we studied, the values of IC50 and Kc for
      the Rp-, Sp- and M-oligodeoxynucleotides were essentially identical. Thus, the
      ability of the phosphorothioate oligodeoxynucleotides we employed, to bind to the
      proteins studied in this work, is virtually independent of P-chirality. Our
      results also imply that the role of the purine and pyrimidine bases in
      oligodeoxynucleotide-protein interactions, as well as the nature of the contact
      points (sulfur versus oxygen) between the oligomer and the protein, may be
      relatively unimportant.

PMID- 7501442
TI  - Only one of four possible secondary structures of the central conserved region of
      potato spindle tuber viroid is a substrate for processing in a potato nuclear
      extract.
AB  - The influence of RNA secondary structure on the substrate activity of a longer
      than-unit length transcript for processing to circular viroids was studied in a
      nuclear extract from potato suspension cells. The nuclear extract was prepared
      according to a modified procedure for a plant transcription extract. The
      transcript of the potato spindle tuber viroid (PSTVd) consists of a monomeric
      molecule with 17 additional nucleotides, thus doubling most of the central
      conserved region of viroids of the PSTVd-class. The transcript can assume four
      different secondary structures, which either co-exist as conformers in solution
      or can be kept as metastable structures after different treatments by temperature
      and/or ionic strength. The structures were analysed by thermodynamic calculations
      and temperature-gradient gel electrophoresis and were confirmed by
      oligonucleotide mapping. Only the so-called extended middle structure was
      processed to exact viroid circles. In this structure the 5'- and 3'-ends are
      branching out from the rod-like viroid structure at the loop starting with
      nucleotide 87. The other structures were processed only if they could be
      rearranged into the active structure.

PMID- 7501443
TI  - Selective binding of looped oligonucleotides to a single-stranded DNA and its
      influence on replication in vitro.
AB  - Complexing of looped and circular oligonucleotides, composed of either 2'
      deoxyribo- or 2'-O-methylribonucleoside units, with completely matching or
      partially mismatching complementary DNA sequences was studied. Melting
      experiments revealed considerable differences among the stabilities of these
      hybrid complexes. Maximum stability and selectivity was displayed by oligomers 2
      and 5. It was concluded that a linear stretch, attached to 1'-O- of 3'
      deoxypsicothymidine unit (Z) increases the selectivity of hybridisation and
      stability of the complex as a whole. This allows one to aim the target DNA very
      precisely at its polyadenine part as well as at adjacent sequence simultaneously.
      Experiments on termination of primer extension catalysed by different DNA
      polymerases--Sequenase, Klenow fragment and Tth--have demonstrated that looped
      oligomer 5, composed of 2'-O-methylribonucleosides appears to be a highly
      selective and potent inhibitor of replication in vitro. Features of looped
      oligonucleotides, composed of 2'-O-methylribonucleosides seem to be useful for
      design of highly specific antigene oligonucleotides.

PMID- 7501444
TI  - The gene for the human architectural transcription factor HMGI-C consists of five
      exons each coding for a distinct functional element.
AB  - The gene on chromosome 12 coding for the human protein HMGI-C has been cloned and
      partially sequenced. It consists of five exons, the first and last of which
      include long untranslated regions. The 5' UTR includes a (CA/T)n tract and a
      polymorphic (CT)n tract. Exons II, III and IV (87, 51 and 33 bp) are dispersed
      over > 30 kb. Exons I-III separately encode the three basic DNA binding domains
      ('A-T hooks'), exon IV encodes an 11 amino acid sequence characteristic of HMGI-C
      and absent from the human HMGI(Y) gene [Friedmann, M., Holth, L. T., Zoghbi, H.
      Y. and Reeves, R. (1993) Nucleic Acids Res., 21, 4259-4267], whilst exon V
      encodes the acidic C-terminal domain, which is subject to multiple
      phosphorylation. The HMGI-C gene is thus a striking example of the separation of
      functional protein elements into different coding exons.

PMID- 7501445
TI  - MEF2 proteins, including MEF2A, are expressed in both muscle and non-muscle
      cells.
AB  - The MEF2 proteins are involved in regulation of many muscle specific genes.
      Although MEF2 RNAs encoding the MEF2A and MEF2D isoforms are ubiquitously
      expressed, the presence of MEF2 proteins in non-muscle cell types has been
      controversial. Here we use a well-characterised antibody in conjunction with DNA
      binding studies to provide evidence that members of the MEF2 family are widely
      expressed in the nuclei of cultured cells and are competent to bind DNA. The data
      show that non-muscle MEF2 complexes contain MEF2A, and that another MEF2 protein,
      probably MEF2D, is also present. These results suggest that MEF2 proteins fulfil
      functions in addition to muscle-specific gene expression.

PMID- 7501446
TI  - A mutant HpaII methyltransferase functions as a mutator enzyme.
AB  - DNA (cytosine-5)-methyltransferases can cause deamination of cytosine when the
      cofactor S-adenosylmethionine (AdoMet) is limiting and thus function as sequence
      specific C-->U mutator enzymes. Here we explored whether mutations causing
      inactivation of the cofactor binding activity of the HpaII methyltransferase,
      thus mimicking conditions of limiting AdoMet concentration, could convert a DNA
      methyltransferase to a C-->U mutator enzyme. We created two mutator enzymes from
      the HpaII methyltransferase (F38S and G40D) which both showed enhanced cytosine
      deamination activities in vitro and in vivo. Interestingly, the G:U mispairs
      generated by these enzymes were not repaired completely in bacteria equipped with
      uracil-DNA glycosylase-initiated repair machinery, giving rise to a potent
      mutator phenotype. This is the first report showing the creation of mutator
      enzymes from a DNA methyltransferase and the demonstration of their mutagenicity
      in living cells.

PMID- 7501447
TI  - Characteristics of triplex-directed photoadduct formation by psoralen-linked
      oligodeoxynucleotides.
AB  - A triplex-forming oligopyrimidine has been attached at its 5'-end to a
      photoreactive psoralen derivative and used to target a sequence which forms part
      of the coding region of the human aromatase gene. The 20 base pair sequence is
      not a perfect triplex target since it contains three pyrimidine interruptions
      within the purine-rich strand. Despite this, we have detected triplex-directed
      photoadduct formation at pH 7.0 between the psoralen-linked oligonucleotide and a
      30mer duplex representing the aromatase target. Photoadduct formation was found
      to be sensitive to pH, temperature, cation concentration and the base composition
      of the third strand. By varying the base sequence of the target duplex around the
      psoralen intercalation site, we have characterised the site and mode of psoralen
      intercalation. The attached psoralen has been found to intercalate at the triplex
      duplex junction with a strong preference for one orientation. We have shown that
      the psoralen will bind at the junction even when there is a preferred TpA step at
      an adjacent site. We have also compared the binding affinity and photoreactivity
      of oligodeoxyribonucleotides linked to two different psoralen derivatives and
      found differences in the rate of crosslinking and the extent of crosslink
      formation. Finally, we have examined oligodeoxyribonucleotides which are attached
      to psoralen by polymethylene linkers of different lengths.

PMID- 7501448
TI  - Human ribonuclease 4 (RNase 4): coding sequence, chromosomal localization and
      identification of two distinct transcripts in human somatic tissues.
AB  - We have isolated a unique genomic fragment encoding human ribonuclease 4 (RNase
      4) of the mammalian ribonuclease gene family, whose members include pancreatic
      ribonuclease, eosinophil-derived neurotoxin, eosinophil cationic protein and
      angiogenin. We have determined that the coding sequence of RNase 4 resides on a
      single exon found on human chromosome 14. The mRNA encoding RNase 4 was detected
      by Northern analysis in a number of human somatic tissues, including pancreas,
      lung, skeletal muscle, heart, kidney and placenta, but not brain; liver
      represents the most abundant source. Interestingly, the mRNA encoding RNase 4 is
      approximately 2 kb in length, which is approximately twice as large as the mRNAs
      encoding other members of this gene family. A larger (approximately 2.4 kb),
      second transcript was detected in hepatic, pancreatic and renal tissues. The
      approximately 2 kb RNase 4 mRNA was detected in cells of the human promyelocytic
      leukemia line, HL-60, that had been treated with dibutyryl-cAMP to promote
      neutrophilic differentiation. In contrast, no mRNA encoding RNase 4 could be
      detected in cells treated with phorbol myristic acid (PMA), an agent promoting
      differentiation toward monocyte/macrophages, suggesting the existence of elements
      regulating tissue specific expression of this gene.

PMID- 7501449
TI  - The tandem repeat AGGGTAGGGT is, in the fission yeast, a proximal activation
      sequence and activates basal transcription mediated by the sequence TGTGACTG.
AB  - Ribosomal protein (rp) genes in the fission yeast Schizosaccharomyces pombe
      display two highly conserved sequence elements in the promoter region. The
      molecular dissection of these promoters revealed that basal transcription is not
      based on a TATA element. The sequence which promotes basal transcription is the
      conserved sequence CAGTCACA or the inverted form TGTGACTG, called the homol D
      box. Upstream of the homol D box a tandem repeat AGGGTAGGGT or the inverted form
      ACCCTACCCT appears in some promoters, called homol E. This element functions in
      the proximal arrangement with homol D as an activation sequence. A compilation of
      homol D and homol E sequences identified in other S.pombe promoters revealed that
      several putative polymerase II and polymerase III promoters display a homol D box
      or the homol E/homol D arrangement.

PMID- 7501450
TI  - DNA CTG triplet repeats involved in dynamic mutations of neurologically related
      gene sequences form stable duplexes.
AB  - DNA triplet repeats, 5'-d(CTG)n and 5'-d(CAG)n, are present in genes which have
      been implicated in several neurodegenerative disorders. To investigate possible
      stable structures formed by these repeating sequences, we have examined d(CTG)n,
      d(CAG)n and d(CTG).d(CAG)n (n = 2 and 3) using NMR and UV optical spectroscopy.
      These studies reveal that single stranded (CTG)n (n > 2) forms stable,
      antiparallel helical duplexes, while the single stranded (CAG)n requires at least
      three repeating units to form a duplex. NMR and UV melting experiments show that
      the Tm increases in the order of [(CAG)3]2 < [(CTG)3]2 << (CAG)3.(CTG)3. The
      (CTG)3 duplex is stable and exhibits similar NMR spectra in solutions containing
      0.1-4 M NaCl and at a pH range from 4.6 to 8.8. The (CTG)3 duplex, which contains
      multiple-T.T mismatches, displays many NMR spectral characteristics similar to
      those of B-form DNA. However, unique NOE and 1H-31P coupling patterns associated
      with the repetitive T.T mismatches in the CTG repeats are discerned. These
      results, in conjunction with recent in vitro studies suggest that longer CTG
      repeats may form hairpin structures, which can potentially cause interruption in
      replication, leading to dynamic expansion or deletion of triplet repeats.

PMID- 7501451
TI  - A novel enzymatic pathway leading to 1-methylinosine modification in Haloferax
      volcanii tRNA.
AB  - Transfer RNAs of the extreme halophile Haloferax volcanii contain several
      modified nucleosides, among them 1-methylpseudouridine (m1 psi), pseudouridine
      (psi), 2'-0-methylcytosine (Cm) and 1-methylinosine (m1l), present in positions
      54, 55, 56 and 57 of the psi-loop, respectively. At the same positions in tRNAs
      from eubacteria and eukaryotes, ribothymidine (T-54), pseudouridine (psi-55), non
      modified cytosine (C-56) and non-modified adenosine or guanosine (A-57 or G-57)
      are found in the so-called T psi-loop. Using as substrate a T7 transcript of
      Haloferax volcanii tRNA(Ile) devoid of modified nucleosides, the enzymatic
      activities of several tRNA modification enzymes, including those for m1 psi-54,
      psi-55, Cm-56 and m1l-57, were detected in cell extracts of H.volcanii. Here, we
      demonstrate that modification of A-57 into m1l-57 in H.volcanii tRNA(Ile) occurs
      via a two-step enzymatic process. The first step corresponds to the formation of
      m1A-57 catalyzed by a S-adenosylmethionine-dependent tRNA methyltransferase,
      followed by the deamination of the 6-amino group of the adenine moiety by a 1
      methyladenosine-57 deaminase. This enzymatic pathway differs from that leading to
      the formation of m1l-37 in the anticodon loop of eukaryotic tRNA(Ala). In the
      latter case, inosine-37 formation preceeds the S-adenosylmethionine-dependent
      methylation of l-37 into m1l-37. Thus, enzymatic strategies for catalyzing the
      formation of 1-methylinosine in tRNAs differ in organisms from distinct
      evolutionary kingdoms.

PMID- 7501452
TI  - Promoter elements of the PHR1 gene of Saccharomyces cerevisiae and their roles in
      the response to DNA damage.
AB  - The PHR1 gene of Saccharomyces cerevisiae encodes the apoenzyme for the DNA
      repair enzyme photolyase. PHR1 transcription is induced in response to 254 nm
      radiation and a variety of chemical damaging agents. We report here the
      identification of promoter elements required for PHR1 expression. Transcription
      is regulated primarily through three sequence elements clustered within a 120 bp
      region immediately upstream of the translational start site. A 20 bp interrupted
      palindrome comprises UASPHR1 and is responsible for 80-90% of basal and induced
      expression. UASPHR1 alone can activate transcription of a CYC1 minimal promoter
      but does not confer damage responsiveness. In the intact PHR1 promoter UAS
      function is dependent upon an upstream essential sequence (UES). URSPHR1 contains
      a binding site for the damage-responsive repressor Prp; consistent with this
      role, deletion or specific mutations of the URS increase basal level expression
      and decrease the induction ratio. Deletion of URSPHR1 also eliminates the
      requirement for UESPHR1 for promoter activation, indicating that the UES
      attenuates Prp-mediated repression. Sequences within UASPHR1 are similar to
      regulatory sequences found upstream of both damage responsive and nonresponsive
      genes involved in DNA repair and metabolism.

PMID- 7501453
TI  - tRNA genes transcribed from the plastid-like DNA of Plasmodium falciparum.
AB  - Besides their mitochondrial genome, malarial parasites contain a second
      organellar DNA. This 35 kb circular molecule has a number of features reminiscent
      of plastid DNAs. Sequence analysis shows that along with other genes the circle
      codes for 25 different tRNAs all of which are transcribed. Six of the tRNAs have
      some unusual features, and one has an intron, the only one found so far on the
      circle. Comparison of codon and anticodon usage indicates that the 25 tRNAs are
      sufficient to decode all the protein genes present on the circle. The maintenance
      of such a parsimonious but complete translation system is further evidence for
      the functionality of the circle.

PMID- 7501454
TI  - Studies of Schizosaccharomyces pombe DNA polymerase alpha at different stages of
      the cell cycle.
AB  - The status of Schizosaccharomyces pombe (fission yeast) DNA polymerase alpha was
      investigated at different stages of the cell cycle. S.pombe DNA polymerase alpha
      is a phosphoprotein, with serine being the exclusive phosphoamino acid. By in
      vivo pulse labeling experiments DNA polymerase alpha was found to be
      phosphorylated to a 3-fold higher level in late S phase cells compared with cells
      in the G2 and M phases, but the steady-state level of phosphorylation did not
      vary significantly during the cell cycle. Tryptic phosphopeptide mapping
      demonstrated that the phosphorylation sites of DNA polymerase alpha from late S
      phase cells were not the same as that from G2/M phase cells. DNA polymerase alpha
      partially purified from G1/S cells had a different mobility in native gels from
      that from G2/M phase cells. The partially purified polymerase alpha from G1/S
      phase cells had a higher affinity for single-stranded DNA than that from G2/M
      phase cells. Despite the apparent differences in cell cycle-dependent
      phosphorylation, mobility in native gels and affinity for DNA, the in vitro
      enzymatic activity of the partially purified DNA polymerase alpha did not appear
      to vary during the cell cycle. The possible biological significance of these cell
      cycle-dependent characteristics of DNA polymerase alpha is discussed.

PMID- 7501455
TI  - Acanthamoeba castellanii contains a ribosomal RNA enhancer binding protein which
      stimulates TIF-IB binding and transcription under stringent conditions.
AB  - The intergenic spacer (IGS) of Acanthamoeba castellanii rRNA genes contains
      repeated elements which are weak enhancers for transcription by RNA polymerase I.
      A protein, EBF, was identified and partially purified which binds to the
      enhancers and to several other sequences within the IGS, but not to other DNA
      fragments, including the rRNA core promoter. No consensus binding sequence could
      be discerned in these fragments and bound factor is in rapid equilibrium with
      unbound. EBF has functional characteristics similar to vertebrate upstream
      binding factors (UBF). Not only does it bind to the enhancer and other IGS
      elements, but it also stimulates binding of TIF-IB, the fundamental transcription
      initiation factor, to the core promoter and stimulates transcription from the
      promoter. Attempts to identify polypeptides with epitopes similar to rat or
      Xenopus laevis UBF suggest that structurally the protein from A.castellanii is
      not closely related to vertebrate UBF.

PMID- 7501456
TI  - High affinity YY1 binding motifs: identification of two core types (ACAT and
      CCAT) and distribution of potential binding sites within the human beta globin
      cluster.
AB  - PCR-assisted binding site selection was used to define the sequence
      characteristics of high affinity YY1 binding sites. Compilation of the sequences
      of 189 selected oligonucleotides containing high affinity YY1 binding sites
      revealed two types of core sequence: ACAT and CCAT. ACAT cores were surrounded by
      other invariant nucleotides, forming the consensus GACATNTT. A search of the 73
      kb human beta-like globin cluster with this consensus revealed eight matching
      motifs, six of which were located within 1-3 kb upstream of the gamma and beta
      genes. CCAT-type cores were more variable in surrounding sequence context; the
      consensus VDCCATNWY was found to fit 89% of the selected CCAT-containing
      oligonucleotides. A search of the human beta globin cluster with CCAT consensus
      sequences revealed 171 potential YY1 binding sites. Several of these were tested
      directly in gel shift assays and confirmed as high affinity YY1 binding sites.
      Finally, a strategy called motif-based phylogenetic analysis was employed to
      determine which of the 179 total sites are evolutionarily conserved. This
      analysis permits the detection of functionally conserved binding sites despite
      sequence differences present between the two species. The 21 conserved sites
      identified will serve as important starting points in further dissection of the
      possible role of YY1 in globin gene regulation.

PMID- 7501457
TI  - An acyclic 5-nitroindazole nucleoside analogue as ambiguous nucleoside.
AB  - Acyclic nucleoside analogues with carboxamido- or nitro-substituted heterocyclic
      bases have been evaluated for their possible use as universal bases in
      oligodeoxynucleotides. The acyclic moiety endows the constructs with enough
      flexibility to allow good base stacking. The 5-nitroindazole analogue afforded
      the most stable duplexes among the acyclic derivatives with the least spread in
      Tm versus the four natural bases. In spite of the acyclic moiety, stabilities are
      comparable with those of duplexes incorporating the recently described 5
      nitroindole nucleoside analogue, but considerably exceed those for the 3
      nitropyrrole analogue.

PMID- 7501459
TI  - Sulphur mustards inhibit binding of transcription factor AP2 in vitro.
AB  - The bifunctional sulphur mustard (bis-(2-chloroethyl)sulphide, HD) and its
      monofunctional analogue (2-chloroethyl ethyl sulphide, CEES) are both vesicants.
      In this study, both mustards were shown to rapidly alkylate the AP2 consensus
      binding sequence incorporated in a 26mer oligonucleotide. The reaction was
      essentially complete within 10 min under the conditions employed in this study
      and -95% of the oligonucleotides were alkylated at least once using 500 microM HD
      and 1 mM CEES. Progressive alkylation of the consensus sequence was parallelled
      by a decrease in transcription factor binding. Under reaction conditions which
      alkylated approximately 95% of the oligonucleotides at least once, the binding of
      cloned human AP2 was reduced by 93 and 76% by HD and CEES, respectively, compared
      with control values. The interference with binding is a result of alkylation of
      the DNA and not damage to the transcription factor by mustard or its hydrolysis
      products. Interference with transcription factor binding would be expected to
      have a profound influence on the ability of the cell to function normally and to
      respond to DNA damage and may contribute significantly to the skin damage
      produced by these compounds.

PMID- 7501460
TI  - Isolation and sequence analysis of rpoH genes encoding sigma 32 homologs from
      gram negative bacteria: conserved mRNA and protein segments for heat shock
      regulation.
AB  - The rpoH genes encoding homologs of Escherichia coli sigma 32 (heat shock sigma
      factor) were isolated and sequenced from five gram negative proteobacteria (gamma
      or alpha subgroup): Enterobacter cloacae (gamma), Serratia marcescens (gamma),
      Proteus mirabilis (gamma), Agrobacterium tumefaciens (alpha) and Zymomonas
      mobilis (alpha). Comparison of these and three known genes from E.coli (gamma),
      Citrobacter freundii (gamma) and Pseudomonas aeruginosa (gamma) revealed marked
      similarities that should reflect conserved function and regulation of sigma 32 in
      the heat shock response. Both the sequence complementary to part of 16S rRNA (the
      'downstream box') and a predicted mRNA secondary structure similar to those
      involved in translational control of sigma 32 in E.coli were found for the rpoH
      genes from the gamma, but not the alpha, subgroup, despite considerable
      divergence in nucleotide sequence. Moreover, a stretch of nine amino acid
      residues Q(R/K)(K/R)LFFNLR, designated the 'RpoH box', was absolutely conserved
      among all sigma 32 homologs, but absent in other sigma factors; this sequence
      overlapped with the segment of polypeptide thought to be involved in DnaK/DnaJ
      chaperone-mediated negative control of synthesis and stability of sigma 32. In
      addition, a putative sigma E (sigma 24)-specific promoter was found in front of
      all rpoH genes from the gamma, but not alpha, subgroup. These results suggest
      that the regulatory mechanisms, as well as the function, of the heat shock
      response known in E.coli are very well conserved among the gamma subgroup and
      partially conserved among the alpha proteobacteria.

PMID- 7501458
TI  - Ig/EBP (C/EBP gamma) is a transdominant negative inhibitor of C/EBP family
      transcriptional activators.
AB  - Analysis of cDNA and genomic clones shows that the murine Ig/EBP (C/EBP gamma)
      gene encodes a small protein with a predicted molecular weight of 16.4 kDa which
      contains C/EBP family basic and leucine zipper domains but lacks the
      transcriptional activation domains present in C/EBP (C/EBP alpha) and NF-IL6
      (C/EBP beta). In transfection assays Ig/EBP is neither an activator nor a
      repressor of transcription; however, Ig/EBP inhibits the transcriptional ability
      of NF-IL6 (C/EBP beta) and C/EBP (C/EBP alpha), acting as a transdominant
      negative regulator. Thus Ig/EBP resembles LIP, another negative regulator of the
      C/EBP family, in both structure and transcriptional activity. Of the three known
      C/EBP family inhibitors, Ig/EBP, LIP and CHOP-10, only Ig/EBP is ubiquitously
      expressed. Therefore, Ig/EBP may act as a general buffer for C/EBP activators in
      many cell types.

PMID- 7501461
TI  - Tm studies of a tertiary structure from the human hepatitis delta agent which
      functions in vitro as a ribozyme control element.
AB  - Viroids and other circular subviral RNA pathogens, such as the hepatitis delta
      agent, use a rolling circle replication cycle requiring an intact circular RNA.
      However, many infectious RNAs have the potential to form self-cleavage
      structures, whose formation must be controlled in order to preserve the circular
      replication template. The native structure of delta RNA contains a highly
      conserved element of local tertiary structure which is composed of sequences
      partially overlapping those needed to form the self-cleavage motif. A bimolecular
      complex containing the tertiary structure can be made. We show that when it is
      part of this bimolecular complex the potential cleavage site is protected and is
      not cleaved by the delta ribozyme, demonstrating that the element of local
      tertiary structure can function as a ribozyme control element in vitro. Physical
      studies of the complex containing this element were carried out. The complex
      binds magnesium ions and is not readily dissociated by EDTA under the conditions
      tested; > 50% of the complexes remain following incubation in 1 mM EDTA at 60
      degrees C for 81 min. The thermal stability of the complex is reduced in the
      presence of sodium ions. A DNA complex and a perfect RNA duplex studied in
      parallel showed a similar effect, but of lesser magnitude. The RNA complex melts
      at temperatures approximately 10 degrees C lower in buffers containing 0.5 mM
      MgCl2 and 100 mM NaCl than in buffers containing 0.5 mM MgCl2 with no NaCl (78.1
      compared with 87.7 degrees C). The element of local tertiary structure in delta
      genomic RNA appears to be a molecular clamp whose stability is highly sensitive
      to ion concentration in the physiological range.

PMID- 7501462
TI  - Catalytic site-specific cleavage of a DNA-target by an oligonucleotide carrying
      bleomycin A5.
AB  - Oligonucleotide reagents have been created which are capable of catalytic site
      specific cleavage of DNA-targets. The oligonucleotide reagent Blm-R-pd(CCAAACA)
      bearing the bleomycin A5 (Blm-RH) residue was used to degrade the DNA-target
      pd(TGTTTGGCGAAGGA). It has been shown that at equimolar reagent: target
      concentration the bleomycin oligonucleotide derivative can repeatedly cleave the
      target at G9, G7, T5, T4 and T3 in site-specific manner. This paper demonstrates
      that with a 10-fold excess of the DNA-target relative to the reagent 30%
      degradation of the target was observed primarily at a single position G7. The
      paper also shows that one reagent molecule containing bleomycin A5 residue was
      capable to degrade three molecules of the DNA-target. The catalytic activity of
      Blm-R-pd(CCAAACA) was the highest in the temperature range close to the melting
      temperature of the reagent-target complex, that is under conditions where the
      oligonucleotide reagent can form a complementary complex and easily dissociate to
      interact with the next molecule of the target. The number of target molecules
      degraded by the bleomycin reagent is limited by the degradation of the antibiotic
      residue itself.

PMID- 7501463
TI  - AFLP: a new technique for DNA fingerprinting.
AB  - A novel DNA fingerprinting technique called AFLP is described. The AFLP technique
      is based on the selective PCR amplification of restriction fragments from a total
      digest of genomic DNA. The technique involves three steps: (i) restriction of the
      DNA and ligation of oligonucleotide adapters, (ii) selective amplification of
      sets of restriction fragments, and (iii) gel analysis of the amplified fragments.
      PCR amplification of restriction fragments is achieved by using the adapter and
      restriction site sequence as target sites for primer annealing. The selective
      amplification is achieved by the use of primers that extend into the restriction
      fragments, amplifying only those fragments in which the primer extensions match
      the nucleotides flanking the restriction sites. Using this method, sets of
      restriction fragments may be visualized by PCR without knowledge of nucleotide
      sequence. The method allows the specific co-amplification of high numbers of
      restriction fragments. The number of fragments that can be analyzed
      simultaneously, however, is dependent on the resolution of the detection system.
      Typically 50-100 restriction fragments are amplified and detected on denaturing
      polyacrylamide gels. The AFLP technique provides a novel and very powerful DNA
      fingerprinting technique for DNAs of any origin or complexity.

PMID- 7501464
TI  - Direct selection of cDNAs using whole chromosomes.
AB  - We have developed a method for direct selection of cDNAs using whole chromosomes
      as target DNA. Double-strand cDNAs were synthesized from human fetal brain
      polyadenylated mRNAs. Flow-sorted chromosomes 17 and 19 were amplified by
      degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) and used to
      capture ds cDNAs by an improved magnetic bead capture protocol. To demonstrate
      the capabilities of this method, the selected cDNAs were used as probes in FISH
      experiments. The selected cDNA populations specifically painted chromosomes 17 or
      19 on metaphase spreads. These results demonstrate that it is possible to do
      chromosome painting using cDNA probes and that this method is a means to rapidly
      select expressed sequences encoded by any portion of the genome.

PMID- 7501465
TI  - Three subunits of the RNA polymerase II mediator complex are involved in glucose
      repression.
AB  - Glucose triggers a complex response in yeast which includes induction and
      repression of a large number of genes. Glucose repression is in part mediated by
      the Mig1 repressor, a zinc finger protein that binds to the promoters of many
      glucose repressed genes. However, some genes that are required for gluconeogenic
      growth are also repressed by a Mig1-independent mechanism. We have isolated
      mutations in three genes that are involved in this Mig1-independent component of
      repression and cloned the genes by complementation. All three genes encode
      subunits of the recently discovered RNA polymerase II mediator complex. Two of
      them are yeast cyclin C and its associated kinase. Disruptions of the three genes
      have identical phenotypes with respect to glucose repression and show no
      synergism with each other. This suggests that these three subunits of the
      mediator complex function closely together in transmitting the transcriptional
      response to glucose.

PMID- 7501466
TI  - A DNase from the trypanosomatid Crithidia fasciculata.
AB  - We have purified to homogeneity a DNase from a Crithidia fasciculata crude
      mitochondrial lysate. The enzyme is present in two forms, either as a 32 kDa
      polypeptide or as a multimer containing the 32 kDa polypeptide in association
      with a 56 kDa polypeptide. Native molecular weight measurements indicate that
      these forms are a monomer and possibly an alpha 2 beta 2 tetramer, respectively.
      The monomeric and multimeric forms of the enzyme are similar in their catalytic
      activities. Both digest double-stranded DNA about twice as efficiently as single
      stranded DNA. They introduce single-strand breaks into a supercoiled plasmid but
      do not efficiently make double-strand breaks. They degrade a linearized plasmid
      more efficiently than a nickel plasmid. Both enzymes degrade a 5'-32P-labeled
      double-stranded oligonucleotide to completion, with the 5'-terminal nucleotide
      ultimately being released as a 5'-mononucleotide. One difference between the
      monomeric and multimeric forms of the enzyme, demonstrated by a band shift assay,
      is that the multimeric form binds tightly to double-stranded DNA, possibly
      aggregating it.

PMID- 7501467
TI  - Synthesis of 2'-modified nucleotides and their incorporation into hammerhead
      ribozymes.
AB  - Several 2'-modified ribonucleoside phosphoramidites have been prepared for
      structure-activity studies of the hammerhead ribozyme. The aim of these studies
      was to design and synthesize catalytically active and nuclease-resistant
      ribozymes. Synthetic schemes for stereoselective synthesis of the R isomer of 2'
      deoxy-2'-C-allyl uridine and cytidine phosphoramidites, based on the Keck
      allylation procedure, were developed. Protection of the 2'-amino group in 2'
      deoxy-2'-aminouridine was optimized and a method for the convenient preparation
      of 5'-O-dimethoxytrityl-2'-deoxy-2'-phthalimidouridine 3'-O-(2-cyanoethyl-N,N
      diisopropylphosphoramidite) was developed. During the attempted preparation of
      the 2'-O-t-butyldimethylsilyl-3'-O-phosphoramidite of arabinouridine a reversed
      regioselectivity in the silylation reaction, compared with the published
      procedure, was observed, as well as the unexpected formation of the 2,2'
      anhydronucleoside. A possible mechanism for this cyclization is proposed. The
      synthesis of 2'-deoxy-2'-methylene and 2'-deoxy-2'-difluoromethylene uridine
      phosphoramidites is described. Based on a '5-ribose' model for essential 2'
      hydroxyls in the hammerhead ribozyme these 2'-modified monomers were incorporated
      at positions U4 and/or U7 of the catalytic core. A number of these ribozymes had
      almost wild-type catalytic activity and improved stability in human serum,
      compared with an all-RNA molecule.

PMID- 7501468
TI  - Purification and characterisation of a DNA helicase, dheI I, from Drosophila
      melanogaster embryos.
AB  - We have purified a DNA helicase (dhel l) from early Drosophila embryos. dhel l co
      purifies with the single-stranded DNA binding protein dRP-A over two purification
      steps, however, the proteins can be separated by their different native molecular
      weight, with dhel l activity co-sedimenting with a polypeptide of approximately
      200 kDa and a sedimentation coefficient of 8.6 S. The enzyme needs ATP hydrolysis
      and divalent cations for displacement activity. It is very salt sensitive, having
      a Mg2+ optimum of 0.5 mM and being inhibited by NaCl concentration > 10 mM. Dhel
      l moves 5'-->3' on the DNA strand to which it is bound. Unwinding activity
      decreases with increasing length of the double-stranded region suggesting a
      distributive mode of action. However, addition of dRP-A to the displacement
      reaction stimulates the activity on substrates with >300 nucleotides double
      stranded region suggesting a specific interaction between these two proteins.

PMID- 7501469
TI  - Excision of specific DNA-sequences from integrated retroviral vectors via site
      specific recombination.
AB  - Vectors for gene transfer and gene therapy were developed which combine the
      advantages of the integrase and recombinase systems. This was achieved by
      inserting two loxP sites for specific DNA excision into an MESV based retroviral
      vector. We show that this 'retroviral lox system' allows the infection of cells
      and the expression of transferred genes. In addition, we constructed an efficient
      retrovirus-based expression system for a modified Cre recombinase. Functional
      tests for DNA excision from integrated retroviral lox vectors were performed by
      the use of a negative selectable marker gene (thymidine kinase). Cre expression
      in cells infected with retroviral lox vectors and subsequent BrdU selection for
      cells in which site-specific recombination has occurred results in large numbers
      of independent cell clones. These results were confirmed by detailed molecular
      analysis. In addition we developed retroviral suicide vectors in which the
      enhancer/promoter elements of both LTRs were replaced by lox sequences. We show
      that lox-sequences located in the LTRs of retroviral vectors are stable during
      retroviral replication. Potential applications of this system would be the
      establishment of revertants of retrovirus-infected cells by controlled excision
      of nearly the complete proviral DNA.

PMID- 7501471
TI  - Two group I introns with a C.G basepair at the 5' splice-site instead of the very
      highly conserved U.G basepair: is selection post-translational?
AB  - In virtually all of the 200 group I introns sequenced thus far, the specificity
      of 5' splice-site cleavage is determined by a basepair between a uracil base at
      the end of the 5' exon and a guanine in an intron guide sequence which pairs with
      the nucleotides flanking the splice-site. It has been reported that two introns
      in the cytochrome oxidase subunit I gene of Aspergillus nidulans and Podospora
      anserina are exceptions to this rule and have a C.G basepair in this position. We
      have confirmed the initial reports and shown for one of them that RNA editing
      does not convert the C to a U. Both introns autocatalytically cleave the 5'
      splice-site. Mutation of the C to U in one intron reduces the requirement for
      Mg2+ and leads to an increase in the rate of cleavage. As the C base encodes a
      highly conserved amino acid, we propose that it is selected post-translationally
      at the level of protein function, despite its inferior splicing activity.

PMID- 7501470
TI  - DNA binding sites for the transcriptional activator/repressor YY1.
AB  - YY1 is ubiquitously expressed zinc finger DNA binding protein. It can act as a
      transcriptional repressor or activator and, when binding at the initiator
      element, as a component of the basal transcription complex. Binding sites for YY1
      have been reported in a wide variety of promoters and they exhibit substantial
      diversity in their sequence. To better understand how YY1 interacts with DNA and
      to be able to predict the presence of YY1 sites in a more comprehensive fashion,
      we have selected YY1 binding sites from a random pool of oligonucleotides. The
      sites display considerable heterogeneity, but contain a conserved 5'-CAT-3' core
      flanked by variable regions, generating the consensus 5'
      (C/g/a)(G/t)(C/t/a)CATN(T/a)(T/g/c)-3', where the upper case letters represent
      the preferred base. This high degree of flexibility in DNA recognition can be
      predicted by modeling the interaction of the four YY1 zinc fingers with DNA and a
      detailed model for this interaction is presented and discussed.

PMID- 7501472
TI  - Alignment editing and identification of consensus secondary structures for
      nucleic acid sequences: interactive use of dot matrix representations.
AB  - We present a computer-aided approach for identifying and aligning consensus
      secondary structure within a set of functionally related oligonucleotide
      sequences aligned by sequence. The method relies on visualization of secondary
      structure using a generalization of the dot matrix representation appropriate for
      consensus sequence data sets. An interactive computer program implementing such a
      visualization of consensus structure has been developed. The program allows for
      alignment editing, data and display filtering and various modes of base pair
      representation, including co-variation. The utility of this approach is
      demonstrated with four sample data sets derived from in vitro selection
      experiments and one data set comprising tRNA sequences.

PMID- 7501473
TI  - Complex patterns of transcription of a Drosophila retrotransposon in vivo and in
      vitro by RNA polymerases II and III.
AB  - The mdg1 retrovirus-like retrotransposon of Drosophila melanogaster was found to
      possess a complex promoter which can be transcribed by both RNA polymerases II
      and III (pol II and pol III). Pol III transcription, which is not typical of
      protein-coding genes, is driven by the sequences located in the long terminal
      repeat (LTR) of mdg1, predominantly within the transcribed region and is
      initiated 10 bp upstream from the regular pol II RNA start site. The pol III RNA
      start site is observed not only in in vitro transcription reactions, but also in
      total RNA isolated from tissue culture cells, larvae, pupae and adult flies. A
      possible role of pol III transcription in mechanisms controlling the expression
      of full-length mdg1-encoded transcripts in the developing fly, which are
      apparently relaxed in cell culture, is discussed.

PMID- 7501475
TI  - Boron-containing oligodeoxyribonucleotide 14mer duplexes: enzymatic synthesis and
      melting studies.
AB  - A set of three 14mer oligodeoxyribonucleotides of sequence d(5'-CTATGGCCTCAG*CT
      3'/3'-GATACCGGAGTCGA-5') containing G* variants either as 2'-deoxyguanosine
      phosphate (unmodified), N7-cyanoborane 2'-deoxyguanosine phosphate (base
      modified) or 2'-deoxyguanosine boranophosphate (backbone-modified) were
      synthesized by template-directed primer extension. Both the N7-cyanoborane 2'
      deoxyguanosine triphosphate and 2'-deoxyguanosine alpha-boranotriphosphate
      nucleotides are good substrates for Sequenase. We infer that a single Sp
      boranophosphate linkage (which has a stereochemistry equivalent to the
      corresponding Rp thiophosphate analog) is formed in the backbone-modified 14mer.
      Thermally induced helix-coil transitions were monitored for the hybridized
      duplexes using UV and circular dichroism (CD) spectroscopy. The CD spectra of the
      two types of boron-modified hybrids closely resemble the unmodified parent
      duplex, forming B-type helices in 150 mM NaCl, 1 mM EDTA, 10 mM phosphate, pH
      7.4, buffer. UV melting results indicate that both hybrids have stabilities
      comparable with the parent duplex as measured by Tm or delta G degree 25. These
      studies indicate that singly modified base- or backbone-boronated DNA are good
      analogs of normal DNA.

PMID- 7501474
TI  - Molecular structure of the halogenated anti-cancer drug iododoxorubicin complexed
      with d(TGTACA) and d(CGATCG).
AB  - 4'-Deoxy-4'-iododoxorubicin, a halogenated anthracycline derivative, is an
      anticancer agent currently under Phase II clinical trials. In preclinical
      studies, it has demonstrated significantly reduced levels of cardiotoxicity
      compared to currently employed anthracyclines. It also has modified
      pharmacological properties resulting in an altered spectrum of experimental
      antitumor activity. The iodine atom at the 4' position of the sugar ring reduces
      the basicity and enhances the lipophilicity of this compound as compared to
      related anthracycline drugs. We report here single crystal X-ray diffraction
      studies of the complexes of 4'-deoxy-4'-iododoxorubicin with the hexanucleotide
      duplex sequences d(TGTACA) and d(CGATCG) at 1.6 and 1.5 A, respectively. The
      iodine substituent does not alter the geometry of intercalation as compared to
      previously solved anthracycline complexes, but appears to markedly affect the
      solvent environment of the structures. This could have consequences for the
      interaction of this drug with DNA and DNA binding proteins in cells.

PMID- 7501476
TI  - Tissue-specific in vivo protein-DNA interactions at the promoter region of the
      Xenopus 63 kDa keratin gene during metamorphosis.
AB  - The Xenopus 63 kDa keratin gene is developmentally regulated and is expressed
      only in the epidermis. Full activation of the 63 kDa keratin gene requires two
      regulatory steps, the first independent and the second dependent on the thyroid
      hormone triiodothyronine (T3). Sequence analysis of a genomic clone of the 63 kDa
      keratin gene identified potential AP2 and SP1 binding sites upstream of the
      transcription initiation site. Electrophoretic mobility shift assays using
      purified or enriched proteins, as well as HeLa nuclear extract in conjunction
      with AP2- and SP1-specific antibodies, have been used to demonstrate that human
      AP2 and SP1 bind elements upstream of the transcription initiation site. In vivo
      footprinting with ligation mediated PCR revealed several footprints, within 350
      bp upstream of the transcription initiation site, including those at the AP2 and
      SP1 sites, that are unique to epidermal cells which express the keratin gene.
      These footprints were absent in blood cells and XL177 cells which do not express
      the gene. Comparison of footprints between cells which express the 63 kDa keratin
      gene at low or high levels showed that the same binding sites are occupied,
      indicating that these sites are required for basal as well as T3-induced
      expression of the 63 kDa keratin gene.

PMID- 7501477
TI  - Single strand targeted triplex formation: targeting purine-pyrimidine mixed
      sequences using abasic linkers.
AB  - Foldback triplex-forming oligonucleotides (FTFOs) that contain an abasic linker,
      [2-(4-aminobutyr-1-yl)-1,3-propanediol] (APD linker), in the Hoogsteen domain
      against pyrimidine bases of a C:G and a T:A base pair were studied for their
      relative stability and sequence specificity of triplex formation. In general, the
      APD linker has less destabilizing effect against a C:G base pair than a T:A base
      pair. Incorporation of three APD linker moieties resulted in decreased binding to
      the target, which was comparable to results observed with three imperfectly
      matched natural base triplets. The APD linker incorporation did not result in the
      loss of sequence specificity of FTFOs, unlike in the case of normal triplex
      forming oligonucleotides (TFOs). The introduction of a positively charged abasic
      linker, however, resulted in decreased stability of the triplex, because of loss
      of hydrogen bonding and stacking interactions in the major groove. The results of
      a molecular modeling study show that APD linker can be readily incorporated
      without any change in the conformation of the natural sugar-phosphate backbone
      conserving overall triple helix geometry. Further, the modeling study suggests a
      hydrogen bond formation between the amino group of linker and N4 of cytosine
      mediated by a solvent molecule (water) in the floor of the base triplet in
      addition to a contribution from the positive charge on the APD linker amino
      group. Either a direct or water-mediated hydrogen bond between the amino group of
      the APD linker and the O4 of thymine is unlikely when the linker is placed
      against a T:A base pair.

PMID- 7501478
TI  - Rapid purification of recombinant Taq DNA polymerase by freezing and high
      temperature thawing of bacterial expression cultures.

PMID- 7501481
TI  - Arrayed preparation of YAC DNA for pulsed field gel analysis.

PMID- 7501480
TI  - High resolution SSCP by optimization of the temperature by transverse TGGE.

PMID- 7501479
TI  - An analysis of differential display shows a strong bias towards high copy number
      mRNAs.

PMID- 7501482
TI  - A simplified approach for isolating oligo(dT) primed cDNA clones with probes
      generated by cDNA selection.

PMID- 7501483
TI  - Efficient amplification using 'megaprimer' by asymmetric polymerase chain
      reaction.

PMID- 7501484
TI  - Upheaval.

PMID- 7501486
TI  - A meta-analysis of nurse practitioners and nurse midwives in primary care.
AB  - This meta-analysis was an evaluation of patient outcomes of nurse practitioners
      (NPs) and nurse midwives (NMs), compared with those of physicians, in primary
      care. The sample included 38 NP and 15 NM studies. Thirty-three outcomes were
      analyzed. In studies that employed randomization to provider, greater patient
      compliance with treatment recommendations was shown with NPs than with
      physicians. In studies that controlled for patient risk in ways other than
      randomization, patient satisfaction and resolution of pathological conditions
      were greater for NP patients. NPs were equivalent to MDs on most other variables
      in controlled studies. In studies that controlled for patient risk, NMs used less
      technology and analgesia than did physicians in intrapartum care of obstetric
      patients. NMs achieved neonatal outcomes equivalent to those of physicians.
      Limitations in data from primary studies precluded answering questions of why and
      under what conditions these outcomes apply and whether these services are cost
      effective.

PMID- 7501485
TI  - Patient outcomes for the chronically critically ill: special care unit versus
      intensive care unit.
AB  - The purpose of this study was to compare the effects of a low-technology
      environment of care and a nurse case management case delivery system (special
      care unit, SCU) with the traditional high-technology environment (ICU) and
      primary nursing care delivery system on the patient outcomes of length of stay,
      mortality, readmission, complications, satisfaction, and cost. A sample of 220
      chronically critically ill patients were randomly assigned to either the SCU (n =
      145) or the ICU (n = 75). Few significant differences were found between the two
      groups in length of stay, mortality, or complications. However, the findings
      showed significant cost savings in the SCU group in the charges accrued during
      the study period and in the charges and costs to produce a survivor. The average
      total cost of delivering care was $5,000 less per patient in the SCU than in the
      traditional ICU. In addition, the cost to produce a survivor was $19,000 less in
      the SCU. Results from this 4-year clinical trial demonstrate that nurse case
      managers in a SCU setting can produce patient outcomes equal to or better than
      those in the traditional ICU care environment for long-term critically ill
      patients.

PMID- 7501488
TI  - Evaluation of a dressing to reduce nipple pain and improve nipple skin condition
      in breast-feeding women.
AB  - This study was designed to evaluate whether maintenance of a moist environment on
      the nipple skin during the first week of breast-feeding would improve damaged
      nipple skin condition, as indicated by the presence of eschar, erythema, and
      fissures, and reduce pain. Fifty White women applied a polyethylene film dressing
      with a perimeter adhesive system to a randomly determined nipple. The dressing
      was present at all times except during feeding. Subjects were assessed every 48
      hours (four times) over 7 days. Serial photographic slides were obtained and
      assessed for skin characteristics. Nipple pain was self-rated with a verbal
      descriptor scale. Use of an occlusive film dressing on nipple skin during the
      first week of breast-feeding appeared to have limited influence on improvement in
      damaged skin condition. Summary scores indicated significant reduction in the
      amount of eschar on the surface of the nipple. There were no differences in
      erythema intensity or fissure severity. Use of a dressing significantly reduced
      nipple pain during the study period.

PMID- 7501487
TI  - Linkages between sexual risk taking, substance use, and AIDS knowledge among
      pregnant adolescents and young mothers.
AB  - This survey examined the relationships of sexual risk taking to substance use and
      AIDS knowledge in pregnant adolescents (n = 58) and nonpregnant young mothers (n
      = 93). Subjects were from predominantly minority backgrounds, were single, and
      ranged in age from 12 to 20 years (M = 16.64). A number of high-risk behaviors
      were reported, including substance use during pregnancy and early parenthood,
      unprotected sexual relations, and multiple (lifetime) sex partners. Current
      pregnancy status, history of marijuana use, and ethnicity were strong predictors
      of having had multiple sex partners. Odds ratios suggested that Black adolescents
      were many times more likely than Whites to have had multiple sex partners.
      Pregnant adolescents were less likely than young mothers (nonpregnant) to have
      had multiple sex partners but more likely to have unprotected sex (i.e., without
      use of a condom). Conversely, young mothers were more likely to have multiple sex
      partners and less likely to have unprotected sex than were pregnant adolescents.
      Those with a history of marijuana use were more likely to have had multiple sex
      partners than were adolescents who had never used this drug. AIDS knowledge was
      not a significant predictor of high-risk sexual behavior.

PMID- 7501490
TI  - Firstborns' behaviors during a mother's second pregnancy.
AB  - Distress and autonomy behaviors were examined in 80 preschool children of
      pregnant mothers and nonexpectant mothers. Four groups of only children
      participated: three groups of 20 children of expectant mothers who were in their
      early, middle, or late stages of pregnancy and a comparison group of 20 children
      of nonexpectant mothers. The groups were balanced for age (young: 18 to 36
      months; old: 37 to 60 months) and sex. At 12 weeks, young firstborn girls were
      more dependent than either young boys or older girls and boys. Firstborns in the
      middle pregnancy group were more dependent at 20 weeks than at 24 and 28 weeks;
      however, boys reacted more to separation and expressed more anger than did girls.
      During the late phase of pregnancy, boys reacted to separation more negatively
      than girls did only at 28 weeks. Old firstborns were generally more autonomous
      than young firstborns; however, by the 32nd week of pregnancy, the groups did not
      differ. Compared with children in the comparison group, those in the early
      pregnancy group showed fewer reactions to separation, and those in the middle
      pregnancy group were less dependent at 24 and 28 weeks. At 38 weeks of pregnancy,
      late pregnancy boys reacted less to separation and expressed less anger than did
      comparison group boys. Late pregnancy girls were angrier than boys in both the
      comparison and pregnancy groups.

PMID- 7501489
TI  - Initiation and frequency of breast expression in breastfeeding mothers of LBW and
      VLBW infants.
AB  - This article is a report of data derived from two investigations. In one study,
      the relationship between early initiation and frequency of breast stimulation to
      feeding pattern at 8 weeks postpartum in mothers of low-birth-weight (LBW; < or =
      2500 g) infants was examined. The other study examined how selected physical,
      psychological, and management variables affect milk volume in mothers of very-low
      birth-weight (VLBW; < or = 1500 g) infants. Initiation and frequency of breast
      stimulation were studied in both investigations. Mothers of LBW (N = 110) and
      VLBW (N = 16) infants had delayed initiation of breast stimulation after delivery
      and low pumping frequency. No relationship was found between early initiation and
      frequency of breast stimulation to feeding pattern in mothers of LBW infants.

PMID- 7501491
TI  - Knowing the patient: a process model for individualized interventions.
AB  - A grounded theory method was used to study nurses' clinical decision making.
      Field notes, in-depth interviews, and documents were analyzed. The beginning
      process model contained the core concept, knowing the patient, a purposeful
      action whereby the nurse uses understanding of the patient's experiences,
      behaviors, feelings, and/or perceptions to select individualized interventions.
      Familiarity and intimacy were the properties of the core process; the patient
      nurse interaction was the context. Three conditions included time, the nurse's
      experience, and other nurses' input. Four strategies facilitated the core
      process: empathizing, matching a pattern, developing a bigger picture, and
      balancing preferences with difficulties. Different strategies were used, as time
      and familiarity with the patient varied.

PMID- 7501492
TI  - An analysis of posthospitalization telephone survey data.
AB  - As part of a study of patient-centered care outcomes that requires the ability to
      be interviewed by telephone after hospitalization, 4,600 adult patients on 118
      medical-surgical units in 17 midwestern hospitals selected by stratified random
      sampling were identified as potential subjects. This article describes response
      rate differences and reasons for nonparticipation by gender, age, ethnicity, and
      race. Issues related to understanding and reporting response rates, reducing
      losses due to ineligibility, dealing with refusals, and tailoring survey
      approaches to special populations are discussed.

PMID- 7501494
TI  - Re: "Motor performance correlates of functional dependence in long-term care
      residents'.

PMID- 7501493
TI  - Social support among impoverished women.

PMID- 7501495
TI  - No child's play.

PMID- 7501496
TI  - Face values.

PMID- 7501498
TI  - A change of part.

PMID- 7501497
TI  - Painful ignorance.

PMID- 7501499
TI  - Helping people with learning disabilities to handle grief.
AB  - This paper examines the scope for using bereavement counselling as an
      intervention for people with learning disabilities who have experienced a
      bereavement. It discusses a range of practical measures which can be introduced
      and highlights the indicators which suggest that interventions are needed.

PMID- 7501500
TI  - The extrapyramidal effects of phenothiazines on patients.
AB  - The phenothiazines have been used for many years in the treatment of psychoses.
      They act by blocking dopamine receptors. Unfortunately, they can also produce
      extrapyramidal side-effects (EPS). The pharmacological origins of these side
      effects are explored in this paper and their presentation, prevalence and
      reversibility are considered. Non-motor adverse effects are also described, and
      implications for patient monitoring and education are also noted.

PMID- 7501501
TI  - Giddens and late modernity: analysing 20th century life.
AB  - The final paper of our series on principal figures in sociology examines the work
      of Anthony Giddens, a British sociologist who is still working. Major components
      of his analysis of late 20th century life are discussed.

PMID- 7501503
TI  - Organ donation. On the cards.

PMID- 7501502
TI  - Evaluation of nurse-led in-patient care.
AB  - This paper describes research aimed at identifying the patient population deemed
      suitable for a nursing-led ward for in-patients. One hundred and sixty-seven
      patients were referred to the unit after a mean stay in acute areas of 26 days.
      The range of stays was zero to 193 days. The mean age of patients was 76 with a
      range from 40 to 97. Ninety-five per cent of patients transferred to the ward had
      been referred for 'rehabilitation'. Certain diagnostic groups such as 'infection'
      and 'injury' which are liable to lead to mobility problems appeared frequently
      among patients transferred. However, a variety of diagnoses were identified. The
      service is potentially suitable for a wide range of patient groups who are
      defined by nursing need, not medical diagnosis.

PMID- 7501504
TI  - Keeping your patients informed.

PMID- 7501505
TI  - Back care: preventing injury.

PMID- 7501506
TI  - Body politic. Faulty powers.

PMID- 7501507
TI  - Students. It's tough at the bottom.

PMID- 7501508
TI  - Students. Fresher approach.

PMID- 7501509
TI  - Agony and ecstasy.

PMID- 7501510
TI  - Beyond belief.

PMID- 7501511
TI  - Across the great divide.

PMID- 7501512
TI  - Poor show.

PMID- 7501513
TI  - Loadsa money.

PMID- 7501514
TI  - Do staff follow guidelines for dealing with MRSA?
AB  - This paper provides an overview of the background of MRSA and its presence in
      hospitals. A small-scale study of practice is described where staff compliance
      with MRSA policy was observed. This paper won the Marian Reed Award, a
      competition run by the West Midlands branch of the Infection Control Nurses'
      Association, which is jointly sponsored by the Midlands-based Hospital Infection
      Research Laboratory and Vernacare.

PMID- 7501515
TI  - Advising patients of the risks.

PMID- 7501516
TI  - Improving hospital policy.
AB  - This paper looks at current procedures in one hospital attempting to control the
      spread of MRSA. It also discusses the information gained from a literature review
      and its application to nursing practice.

PMID- 7501517
TI  - Healthy democracy.

PMID- 7501518
TI  - Making sense of... photorefractive keratectomy.
AB  - The technique of photorefractive keratectomy (PRK) represents a major development
      in ophthalmology. Using lasers, PRK involves reshaping the cornea so that its
      refractive power is increased. Currently PRK can only be used to correct myopia
      and astigmatism, but hypermetropia may also be corrected by PRK in the near
      future.

PMID- 7501519
TI  - Applying nasal intermittent positive pressure ventilation.
AB  - This paper looks at the use of nasal intermittent positive pressure ventilation,
      an intervention which can improve the quality of life for patients who suffer
      from chronic respiratory failure. The practicalities and management of such
      patients are described and the benefits.

PMID- 7501520
TI  - Using the named nurse system to improve patient care.
AB  - The named nurse initiative within the Patient's Charter has attracted criticism
      as a public relations exercise. None the less, it is argued that it provides an
      opportunity for nurses to be clear about what they contribute to the overall care
      of patients. Moreover, monitoring systems for the initiative can be used to help
      staff gather evidence to help improve care.

PMID- 7501521
TI  - Habit-forming questions.

PMID- 7501522
TI  - Debilitating discrimination.

PMID- 7501523
TI  - Able to care.

PMID- 7501525
TI  - Skin care: principles of hand-washing.

PMID- 7501526
TI  - I'm a doctor, hit me.

PMID- 7501524
TI  - Who was Tourette?

PMID- 7501528
TI  - The aftermath of diagnosis.

PMID- 7501527
TI  - Shaping up the depot.

PMID- 7501529
TI  - Multiple meanings of pain and complexities of pain management.
AB  - Pain is a human experience with many different definitions and meanings. Under
      the influence of science these meanings multiplied and added complexity to the
      process of managing pain as a clinical problem. Over the last four decades nurses
      have made important contributions to pain knowledge and pain management through
      research and clinical innovation. Nurses are pivotal providers in the
      implementation of effective pain management programs and in fostering
      multidisciplinary efforts to improve the services currently available to cancer
      patients and their families.

PMID- 7501530
TI  - The importance of nursing research design and methods in cancer pain management.
      Enhancing care.
AB  - Cancer is diagnosed currently in more than 1 million Americans every year and
      cancer pain is experienced by patients in all stages of the disease. Even though
      research indicates that optimal pharmacologic management alone can provide
      adequate relief for 70% to 90% of these patients, and additional relief can be
      obtained from nonpharmacologic interventions, the problem of pain continues to
      exist. This article focuses on the contributions of nurse scientists to the study
      of cancer pain during the last 5 years. Selected contributions of nursing
      research designs and methods to the understanding of pain caused by cancer and
      cancer treatment modalities are reviewed. Limitations of present methodologic
      approaches to the study of cancer pain and gaps in nursing knowledge are
      examined. Recommendations for future nursing research designs and methods used to
      study nursing management of cancer pain and the implications of projected future
      treatment modalities also are discussed.

PMID- 7501531
TI  - The impact of pain on quality of life. A decade of research.
AB  - Pain and the quality of life are closely related. This article summarizes a
      series of studies conducted over the last decade contributing to the
      understanding of the pain and quality of life relationship. Details about the
      meaning of pain, the experience of pain in children, and the impact of pain on
      the family are presented. Information obtained from research studies led to the
      development of pain education programs that strengthen direct nursing care of
      patients and families experiencing cancer pain.

PMID- 7501532
TI  - Family members' perceptions of cancer pain. Comparisons with patient sensory
      report and by patient psychologic status.
AB  - This study was the first to compare patient and family member perceptions of
      sensory pain and to describe the relationships between these perceptions and
      psychological factors in patients with lung cancer and pain. Our findings
      indicate that family members understand the patient's pain location about 75% of
      the time; however, family members rarely understand the patient's pain intensity,
      pain quality, or pain pattern. Our findings also indicate that family members
      tend to overestimate strategies used by patients to cope with pain, especially in
      patients with low levels of anxiety and in patients with an internal locus of
      control. Although findings from this study differ from some previous studies, our
      study provides additional data to suggest that discrepancies may exist between
      family member and patient perceptions of the cancer pain experience. Nurses need
      to be aware of potential discrepancies and to combine assessment information from
      both patients and family members when developing pain management interventions.

PMID- 7501533
TI  - Patterns of pain experiences and use of analgesics among hospitalized cancer
      patients in Korea.
AB  - Four hundred fifty cancer patients were selected from two public university
      hospitals and two private university hospitals in a large-sized city (Seoul) as
      well as a medium-sized city (Taegu) in Korea. Patients were interviewed regarding
      their experiences with pain during hospitalization and their medical records were
      reviewed. About 70% of cancer patients had cancer-related pain. Over 50% of the
      patients with pain had metastases. These findings indicate that Korean patients
      have relatively advanced cancer status and more severe pain compared with cancer
      patients hospitalized for treatment in the United States. The mean daily morphine
      equivalent dose, however, was 55.7 mg, which is lower than practices in the
      United States. Health professionals seem to rely on their preconceptions about
      pain and pain management. The results suggest the need for standardization of
      pain assessment, individualization of pain treatment, and development of
      educational programs for pain relief measures to improve the care of cancer
      patients who suffer from pain.

PMID- 7501534
TI  - Impact of surgery on head and neck cancer patients and their caregivers.
AB  - Little information has been gathered about the experiences of head and neck
      cancer patients at the time of their initial surgery and about the ramifications
      of the surgery for patients and their caregivers. The authors discuss the pain
      experience of patients, the relationship of pain to their fatigue and negative
      mood, and the concerns of both patients and caregivers. Family caregivers are
      expected to take responsibility for the patients, and it is important for nurses
      to recognize the concerns of both patients and caregivers at the time of
      discharge into the home setting.

PMID- 7501535
TI  - Unscheduled readmissions for uncontrolled symptoms. A health care challenge for
      nurses.
AB  - The purpose of this study was to measure the impact of nursing strategies to
      improve cancer pain management on hospital readmission for uncontrolled pain.
      Strategies include implementing a pain resource nurse program (PRN), making pain
      management a focus in the continuous quality improvement process of the
      institution and creating a supportive care service. Admissions were compared
      before and after implementation of the strategies. Results for 1989 to 1990
      revealed 5772 total admission with 4.4% (255) admissions for uncontrolled pain;
      results for 1992 to 1993 revealed 4066 total admissions with 3.0% (121)
      admissions for uncontrolled pain. Findings indicate that strategies were
      effective in reducing the number of readmissions for uncontrolled pain.

PMID- 7501536
TI  - Outcomes that provide evidence of change in cancer pain management.
AB  - Making improvements in the management of cancer pain is a complex process
      involving patient and professional factors. This article reviews the types of
      outcome measures that have been used to document improvement in cancer pain
      management. Examples from several studies are provided to illustrate the
      difficulty and benefit of documenting evidence of change in professional practice
      related to cancer pain management.

PMID- 7501537
TI  - Relaxation and the relief of cancer pain.
AB  - Progressive muscle relaxation combined with guided imagery has the potential to
      promote relief of cancer pain. The techniques appear to produce a relaxation
      response that may break the pain-muscle-tension-anxiety cycle and facilitate pain
      relief through a calming effect. The techniques can be taught by nurses and
      readily learned by patients. The techniques provide a self-care strategy that, to
      a limited extent, shifts the locus of control from clinician to patient.

PMID- 7501539
TI  - Sublingual and oral morphine administration. Review and new findings.
AB  - Clinical reports rave about the efficacy of sublingual morphine, but most
      research data suggest that sublingual morphine lacks the necessary physical
      characteristics to be absorbed through sublingual tissues. This article clarifies
      these assertions by reviewing the clinical literature that supports sublingual
      administration, the theories relevant to sublingual morphine administration, and
      the pharmacokinetic research that supports or negates the benefit of this route.
      Recommendations for clinical nursing practice are provided to guide decision
      making in care of patients with cancer pain.

PMID- 7501538
TI  - An algorithmic approach to cancer pain management.
AB  - Pain and symptom management is an important aspect of hospice care. In an attempt
      to deliver consistent and high-quality interventions in a timely manner
      algorithms for pain and symptom management were developed. We have used these
      algorithms for the past 2 years with successful outcomes. Development of the pain
      and symptom management algorithms has contributed to the development of a
      standardized plan for symptom management. The algorithms offer the flexibility to
      respond to individual differences found in our patient population. Working
      together, physicians, nurses, and pharmacists offer a team approach to patient
      care.

PMID- 7501540
TI  - Pharmacologic management of cancer pain.
AB  - The satisfactory management of pain associated with neoplastic disease is one of
      the most difficult problems encountered by the clinician. Adequate knowledge of
      the pathophysiology of pain, the cause and presentation of different pain types,
      and the mechanisms of action of medications is necessary for sound clinical
      decisions. Effective pain management has a profound impact on the patient's
      quality of life and may reduce suffering.

PMID- 7501541
TI  - Current status of neoadjuvant therapy in localized prostate cancer.

PMID- 7501542
TI  - Expression of estrogen receptor in diseased human prostate assessed by non
      radioactive in situ hybridization and immunohistochemistry.
AB  - To understand the role of estrogen in the pathogenesis of benign prostatic
      hyperplasia, expressions of estrogen receptor (ER) mRNA and ER protein by in situ
      hybridization and by immunohistochemistry, respectively, were investigated in
      human prostatic tissues. In non-malignant region, ER mRNA and ER protein were
      found in cytoplasm and nucleus, respectively, of stromal cells, but not in
      glandular epithelial and basal cells. In benign regions, ER mRNA/ER protein
      positive cells were found in fibromyoadenomatous and myoadenomatous hyperplasia,
      but not in adenomatous hyperplasia. A striking feature was periacinar arrangement
      of ER mRNA/ER protein positive stromal cells in all prostate carcinoma treated
      with androgen withdrawal. The ER mRNA/ER protein positive cells were
      immunohistochemically identified as fibroblasts, myoblasts, and smooth muscle
      cells. These results indicate that stromal cells are the primary target of
      estrogen in prostate, and that androgen withdrawal upregulates the expression of
      ER gene.

PMID- 7501543
TI  - Retinoblastoma gene mutations in primary human prostate cancer.
AB  - Structural alterations in the entire coding regions (exons 1 to 27) of the
      retinoblastoma (RB) gene in primary human prostate cancers were investigated,
      using polymerase chain reaction and single strand conformational polymorphism
      analysis of RNA. Of 25 samples obtained from patients, four (16.4%) were found to
      have RB alterations. DNA sequencing of the PCR products revealed point mutations
      resulting in single amino-acid substitutions of exons 6 and 19 in two cases, and
      base deletions of exons 8 and 17 in two cases. Two of four cases with RB
      mutations were moderately differentiated localized tumors and other two with RB
      mutations were poorly differentiated tumors with metastases. Our results suggest
      that RB gene mutation is involved in progression steps of prostate
      carcinogenesis.

PMID- 7501544
TI  - Effects of a new steroidal antiandrogen, TZP-4238 (17 alpha-acetoxy-6-chloro-2
      oxa-4, 6-pregnadiene-3, 20-dione), on spontaneously developed canine benign
      prostatic hyperplasia.
AB  - The effects of the new steroidal antiandrogen, TZP-4238 on spontaneously
      developed canine prostatic hyperplasia (BPH) were studied in comparison with
      those of chlormadinone acetate (CMA), a steroidal antiandrogen used for the
      treatment of BPH and prostatic cancer in Japan. Aged beagle dogs (5-9 years old)
      with spontaneously developed BPH (mean prostate volume, 17.7ml) were treated
      orally with a placebo, TZP-4238 (0.1 mg/kg/day, 0.01 mg/kg/day), or CMA (3
      mg/kg/day), for 25 weeks. Prostate volume was measured by transrectal
      ultrasonography before treatment and every 5 weeks during treatment. TZP-4238
      produced a regression in spontaneously developed canine BPH, its effects being
      more potent than those of CMA. TZP-4238 reduced the content of testosterone,
      dihydrotestosterone (DHT) and androgen receptor in the prostates of these
      animals, suggesting antiandrogenic mechanisms of the agent. TZP-4238 also
      appeared to reduce 5 alpha-reductase activity by prevention of the androgen
      action in prostate as described above.

PMID- 7501545
TI  - DNA heterogeneity determined by flow cytometry in prostatic adenocarcinoma-
      necessitating multiple site analysis.
AB  - Although DNA ploidy analysis of prostate cancer is generally associated with
      grade, stage, clinical outcome, and responsiveness to androgen therapy, one
      possible reason cited for contrary reports may be tumor heterogeneity. A
      preliminary report using flow cytometric analysis of punch biopsies demonstrated
      DNA heterogeneity in five of nine patients. We evaluated 75 patients by cutting
      whole mounts of formalin fixed prostatectomy tissue every 0.6 cm. All malignant
      areas and a selected normal area were circumscribed, excised, remounted, and 1-3
      50 mu thick sections removed. The nuclei were extracted by a Hedley technique and
      the DNA stained with propidium iodide. Each whole mount had an average of 1
      distinct malignant area (range of 1-6 areas per whole mount block). Nuclei were
      analyzed on a Becton Dickinson (San Jose, CA) FACScan flow cytometer equipped
      with RFIT DNA software program. After excluding histograms with CVs > 8.0% and/or
      "suspicious" diploid histograms having a right "shoulder," 75 or 87 patients
      still had > or = 2 malignant sites available for analysis (average 4, range 2-9
      malignant sites/patient). The 322 histograms had an average CV of 4.4%. Thirty of
      75 patients (40%) showed DNA heterogeneity in multiple samples taken from the
      same prostate. There were 37 prostates with only diploid (D), 1 with only
      tetraploid (T), 7 with only aneuploid (A), 20 with D plus A, 7 with D plus T, 2
      with D plus T plus A, and 1 with a D plus suspected hypodiploid DNA content.
      Exclusion of the tetraploid and "near diploid aneuploid" cases still resulted in
      16% (12/75) of the patients having a diploid versus aneuploid DNA content
      heterogeneity. Because 40% of the prostates contained a different ploidy
      depending on which area was sampled, this report suggests multiple sites of
      malignancy must be analyzed to more accurately assess the ploidy status of
      prostatic adenocarcinoma.

PMID- 7501546
TI  - Adenocarcinoma of the prostate metastatic to the choroid of the eye.
AB  - We report an unusual case of bilateral choroidal masses developing in a patient
      with metastatic prostate cancer. Visual symptoms resolved and ocular mass lesions
      regressed after initiating total androgen deprivation. The natural history and
      management of choroidal metastatis originating from prostate cancer is discussed.

PMID- 7501547
TI  - Mothers' knowledge and practices related to sun protection in Greece.
AB  - We attempted to estimate the level of Greek mothers' knowledge relating to the
      harmful effects of sunlight and whether this knowledge led to protective measures
      for them and their children. Between September and November 1993, 315 mothers
      were randomly selected from the outpatient department of our hospital and
      interviewed by questionnaire about themselves and their children (56% boys, 44%
      girls, ages 1-12 yrs). Knowledge was estimated by an index score that for 28% of
      the mothers was considered poor, for 50% moderate, for 16% good, and for only 6%
      very good or excellent. The score was positively associated with parent
      education, urban residence, mother's job relevant to the cosmetics industry or
      the mass media, and history of sunburn in one or both parents. Scores were also
      established for sunlight-protective measures taken for themselves (28% poor, 45%
      moderate, 27% just good) and for their children (24% poor, 46% moderate, 30% just
      good). These scores were significantly associated only with mothers' knowledge of
      sun protection. Mothers who used sun protection for themselves also applied it to
      their children. This study shows that mothers in Greece should be encouraged both
      to increase their knowledge of sun protection and steadily incorporate it into
      their lifestyle.

PMID- 7501548
TI  - Infantile acropustulosis in six immigrant children.
AB  - Infantile acropustulosis is a recurrent, pruriginous, vesiculopustular eruption
      of the palms and soles first described in 1979. We report six cases of infantile
      acropustulosis in recently emigrated children treated for scabies. Clinical
      follow-up was obtained by questionnaire addressed to patients' families and
      general practitioners. Our study suggests infantile acropustulosis is frequent in
      immigrant infants and could be a non-specific hypersensitivity reaction to
      Sarcoptes scabiei.

PMID- 7501549
TI  - Painful fingers, heat intolerance, and telangiectases of the ear: easily ignored
      childhood signs of Fabry disease.
AB  - Generalized anhidrosis with heat collapse, painful fingers, and angiokeratomas
      were the presenting signs in a 23-year-old man who was shown by enzyme studies
      and electron microscopy to have Fabry disease. His 6-year-old brother had the
      early diagnostic findings of episodic painful fingers, heat intolerance, and
      retroauricular telangiectasia. Both had an absence of alpha-galactosidase. Over 6
      years of observation, the older brother developed progressive renal failure and
      the younger one developed acrodynia and anhidrosis. Their mother had diminished
      alpha-galactosidase activity and several angiomatous papules on one breast. A
      review of Fabry disease emphasizes the need for skin inspection for angiomas and
      telangiectasia, and enzyme assay in patients with inexplicable complaints or
      findings. Carrier females are most easily recognized by the presence of unique
      corneal opacities.

PMID- 7501550
TI  - Necrobiosis lipoidica diabeticorum in children and adolescents: a clue for
      underlying renal and retinal disease.
AB  - The prevalence of persistent microalbuminuria, retinopathy, and peripheral and
      autonomic neuropathy was assessed in 18 children and adolescents with type 1
      (insulin-dependent) diabetes mellitus (IDDM) who suffered from necrobiosis
      lipoidica diabeticorum (NLD) and in 40 diabetics without NLD, matched for sex,
      age, duration of disease, and metabolic control. The mean +/- SD age of the
      patients was 15.1 +/- 8.6 years (range 7.9-23.9 yrs) and their duration of IDDM
      was 10.9 +/- 8.1 years (range 7.1-21.0 yrs). Their mean glycosylated hemoglobin
      level was 9.9 +/- 5.0% (7.3-16.6%) and their fructosamine level was 274 +/- 180
      mumol/L (199-466 mumol/L). Patients with NLD had a higher frequency of persistent
      microalbuminuria (p < 0.001) and retinopathy (p < 0.001) than those without NLD.
      Our study suggests that children as well as adult diabetics with NLD can be at
      high risk for nephropathy and retinopathy; NLD can be a clue for diabetic
      nephropathy and retinopathy.

PMID- 7501551
TI  - Infantile acute hemorrhagic edema: a variant of leukocytoclastic vasculitis.
AB  - Infantile acute hemorrhagic edema (IAHE) is a leukocytoclastic vasculitis that is
      confined to the skin without visceral involvement. Edema and purpuric lesions
      characterize the disease. The disorder has a dramatic onset, with a short, benign
      course and spontaneous resolution within several weeks. The clinical similarities
      between IAHE and Henoch-Shonlein purpura have been discussed in the literature.
      We report three infants with IAHE and discuss the clinical, laboratory, and
      histopathologic features of the disease. We suggest that it should be regarded as
      a separate entity for appropriate diagnostic investigations and therapy.

PMID- 7501552
TI  - Extensive symmetric truncal aplasia cutis congenita without fetus papyraceus or
      macroscopic evidence of placental abnormalities.
AB  - Aplasia cutis congenita is a rare disorder characterized by localized absence of
      skin at birth. Type V in Frieden's classification, which is associated with fetus
      papyraceous or placental infarcts, occurs as a large cutaneous defect on the
      trunk and extremities. The patient we report had a lesion affecting the trunk and
      extremities symmetrically, with no family history of the disorder or chromosomal
      abnormalities. In our opinion, despite the absence of fetus papyraceous or
      placental infarct, this patient's condition can be classified as type V.

PMID- 7501553
TI  - Congenital erythrodermic psoriasis: case report and literature review.
AB  - A 4-year-old girl was seen in our department for erythroderma, palmoplantar
      hyperkeratosis, and scalp desquamation present since birth. The dermatosis had
      run an intermittent course, with exacerbations after infections and spontaneous
      remissions. A specimen from a skin biopsy performed at 1 year of age showed the
      characteristic features of psoriasis, findings that were confirmed in our biopsy
      specimen. Treatment with acitretin controlled the outbreaks. At 7 years of age
      she has developed, for the first time, plaque type psoriasis. Congenital
      erythroderma is an unusual form of psoriasis with a wide differential diagnosis.

PMID- 7501554
TI  - Cutaneous histoplasmosis in a child with hyper-IgM.
AB  - Immunodeficiency with hyperimmunoglobulinemia M is a rare disease characterized
      by very low levels of IgG and IgA and normal or high levels of serum IgM and IgD.
      Recurrent and severe systemic infections with pathogenic bacteria are frequent if
      immunoglobulin replacement therapy is not given. Histoplasmosis is a systemic
      granulomatous mycosis due to Histoplasma capsulatum and characterized by a
      particular affinity for the reticuloendothelial system. Glabrous skin involvement
      in histoplasmosis is highly unusual except in patients with advanced human
      immunodeficiency viral disease. Cutaneous histoplasmosis and granulomatous
      reaction were diagnosed in a 5-year-old boy with hyper-IgM disease. The lesion
      improved after oral ketoconazole therapy. To our knowledge, this is the first
      case of cutaneous histoplasmosis associated with hyper-IgM to be reported.

PMID- 7501555
TI  - Epidermolysis bullosa junctionalis associated with urinary bladder exstrophy: a
      case report.
AB  - We report the second infant of nonconsanguineous parents with epidermolysis
      bullosa junctionalis associated with urinary bladder exstrophy, epispadias,
      anteriorized anus, and bilateral inguinal hernias. The family history also
      included the death of a maternal cousin due to epidermolysis bullosa. Our
      diagnosis was based on electron microscopy and immunofluorescence evidence. This
      patient is reported because of the rarity of this constellation of findings.

PMID- 7501556
TI  - Congenital glomangioma: case report and review of the world literature.
AB  - Glomangiomas, or multiple glomus tumors, occur in disseminated, localized, or
      congenital plaquelike forms. The first two cases of congenital plaquelike
      glomangioma were described in 1990. We report a 9-year-old girl with a
      congenital, violaceous, 75-cm2 indurated plaque of the left abdomen that showed
      the classic histologic findings of glomangioma. In our review of the world
      literature, we found 11 additional, well-documented cases of glomangioma present
      at birth. Ten of these patients had violaceous indurated plaques, and the other
      two had clusters of discrete nodules. The majority of lesions were painless and
      enlarged with body growth. Many patients developed satellite lesions at sites
      distant from the original glomangiomas later in life. Family history of
      glomangioma was positive in 4 of the 12 patients.

PMID- 7501557
TI  - Unilateral Beau's lines in childhood reflex sympathetic dystrophy.
AB  - Reflex sympathetic dystrophy is characterized by severe pain and autonomic
      dysfunction in a limb, usually after an injury. We describe a patient with
      childhood reflex sympathetic dystrophy with unilateral Beau's lines on the nails
      of the affected hand. Unilateral Beau's lines have not been described previously
      in this condition to our knowledge, and we discuss their possible pathogenesis.

PMID- 7501558
TI  - Congenital apocrine hamartoma: an unusual clinical variant of organoid nevus with
      apocrine differentiation.
AB  - Congenital apocrine hamartomas are rare tumors of the skin composed of mature
      apocrine glands in the papillary and reticular dermis. Several cases have been
      reported in the literature but few were of uniform clinical appearance. The term
      apocrine nevus has been used interchangeably with apocrine hamartoma in the
      literature, however, based on their distinctive morphologies we believe they are
      different entities. We describe a 7-year-old girl with a congenital apocrine
      hamartoma of the left cheek. A stained biopsy specimen from the lesion revealed
      large mature apocrine glands with decapitation secretion in the dermis. The
      presence of periodic acid-Schiff-positive, diastase-resistant granular material
      in the apical cytoplasm of some secretory cells helped differentiate these as
      apocrine glands. We think this lesion may represent a form of organoid nevus with
      pure apocrine differentiation.

PMID- 7501560
TI  - Cervical occult spinal dysraphism: MRI findings and the value of a vascular
      birthmark.
AB  - Spinal dysraphism is easily recognized in the overt form as a meningocele or
      myelomeningocele. The closed form or occult spinal dysraphism (OSD) can be
      overlooked. It occurs predominantly at the lumbosacral level, but OSD at the
      cervical level, although very rare, also occurs. The value of magnetic resonance
      imaging investigations in preparation for surgical treatment is emphasized. We
      discuss the value of various midline posterior skin anomalies as indicators of an
      underlying developmental defect in the neural axis. Hallmarks for OSD in the
      inferior third of the back are well known. They can also occur at the cervical
      level. Among these warning cutaneous midline changes, a vascular stain alone is
      rarely a clue for OSD whatever the spinal level involved, and specifically in the
      nuchal area.

PMID- 7501559
TI  - Kaposi sarcoma in a Thai boy with acquired immunodeficiency syndrome.
AB  - Kaposi sarcoma is rare in children with acquired immunodeficiency syndrome
      (AIDS). We report a 3-year-old boy with AIDS and Kaposi sarcoma of the skin and
      lymph node. This patient is the only one with this disease among 278 children
      with AIDS who have been seen at Chiang Mai University Hospital. He responded well
      to intravenous vincristine.

PMID- 7501562
TI  - True tail in a newborn.
AB  - Human true tail is a rarely reported anomaly that may have a marked psychologic
      impact on the patient's family and may be associated with other congenital
      anomalies. A true tail in a newborn girl is reported, and findings from a review
      of the literature are summarized. The clinical and pathologic differential
      diagnoses are discussed, as they might affect the management and prognosis of
      this congenital malformation.

PMID- 7501561
TI  - Placental nevus cells associated with giant congenital pigmented nevi.
AB  - We present an infant born with a giant congenital pigmented nevus. The placenta
      revealed nests of nevus cells in the chorionic villi on the fetal side of
      circulation. These findings are consistent with four reports in the literature to
      date.

PMID- 7501563
TI  - Neurofibromatosis-Noonan syndrome.
AB  - Type I neurofibromatosis (NF-1) and Noonan syndrome (NS) are two fairly common
      genetic disorders. Patients with features of both disorders have been described,
      but considerable variability of phenotypic expression occurs. As a result, the
      correct nosology of this syndrome is uncertain. We present a patient with full
      expression of both NF-1 and NS phenotypes, and discuss the debate regarding the
      genetics of the combined syndrome.

PMID- 7501564
TI  - Upper extremity atrophy associated with a giant congenital melanocytic nevus.
AB  - Persistent limb atrophy in association with a giant congenital melanocytic nevus
      is described. This association has not been reported previously.

PMID- 7501565
TI  - Infantile acropustulosis--how often is it a sequela of scabies?

PMID- 7501566
TI  - What syndrome is this? Rothmann-Thomson syndrome.

PMID- 7501567
TI  - Papulosquamous plaques in a mother and newborn son.

PMID- 7501568
TI  - Concurrent appearance of alopecia areata in siblings.

PMID- 7501570
TI  - Allopurinol for Old World cutaneous leishmaniasis.

PMID- 7501569
TI  - Nevus depigmentosus associated with hemihypertrophy of the limbs.

PMID- 7501571
TI  - Gastrointestinal complaints in individuals with hypohidrotic ectodermal dysplasia
      (Christ-Siemens-Touraine syndrome). National Foundation for Ectodermal
      Dysplasias.

PMID- 7501572
TI  - Outcome of nail dystrophies in children.

PMID- 7501573
TI  - New oral agents for type II diabetes. Taking a more aggressive approach to
      therapy.
AB  - Status quo obviously is not optimal in the management of patients with non
      insulin-dependent diabetes, given the fact that the average hemoglobin A1c value
      in this diabetic population is between 9% and 10%. There is an impetus,
      therefore, to move up the treatment ladder more quickly than at present. The
      availability of new oral hypoglycemic agents provides the potential for expanding
      the role of this category of agents and for improving overall glycemic control in
      these patients.

PMID- 7501574
TI  - Variceal bleeding. Can it be prevented?
AB  - Esophageal and gastric varices develop as a consequence of portal hypertension
      and advanced chronic liver disease. Bleeding from these varices causes high
      mortality and morbidity. The exact mechanism leading to rupture of varices is
      unknown, but portal pressure, intravariceal pressure, and increased variceal wall
      tension may be factors. Large varices are most likely to bleed, and some studies
      suggest that red wales on varices may predict bleeding risk. Surgery and
      endoscopic sclerotherapy are not useful for preventing initial variceal bleeding,
      but nonselective beta-adrenergic blocking drugs have been shown to be beneficial
      in primary prophylaxis. Proper selection of patients and careful monitoring of
      side effects during treatment enhance successful outcomes.

PMID- 7501575
TI  - Variceal bleeding. What are the treatment options?
AB  - Management of variceal hemorrhage is complex and can be difficult. Initially, the
      severity of the bleeding episode must be assessed and the intravascular volume
      repleted. Several treatment options are available. A trial of pharmacologic
      therapy (eg, vasopressin) may control acute bleeding. Temporary balloon tamponade
      of varices is helpful if bleeding continues. Endoscopic sclerotherapy and
      variceal ligation appear to be equally beneficial, although fewer complications
      have been reported with the latter. Transjugular intrahepatic portacaval shunt
      (TIPS) and portal-systemic shunt surgery are alternatives when endoscopic therapy
      fails; TIPS is preferred in patients awaiting liver transplantation. Ultimately,
      the choice of treatment is based on the expertise available at each medical
      center.

PMID- 7501576
TI  - Will Congress shred the safety net?

PMID- 7501577
TI  - Unstable angina pectoris. What is the likelihood of further cardiac events?
AB  - Wide variation in severity of unstable angina requires an individualized
      approach. The goals are to stabilize the patient's condition and prevent
      progression to acute myocardial infarction or death. The following points
      summarize the current status of diagnosis and treatment: Patients suspected of
      having unstable angina but thought to be at low risk can be discharged after
      clinical evaluation if further outpatient evaluation within 72 hours is
      scheduled. Patients thought to be at intermediate or high risk should be
      hospitalized. Thrombolytic therapy should not be administered without evidence of
      acute myocardial infarction. Assessment of prognosis by noninvasive testing often
      aids in selection of appropriate therapy. Coronary angiography is appropriate in
      patients judged to be at high risk for cardiac complications on the basis of
      their clinical course or results of non-invasive testing. Coronary artery bypass
      grafting should be recommended in almost all patients with left main coronary
      artery disease and many with multivessel disease, especially those with left
      ventricular dysfunction. Percutaneous transluminal coronary angioplasty is also
      effective in selected patients. The discharge care plan should include continued
      monitoring of symptoms, appropriate drug therapy (including aspirin), and risk
      factor modification.

PMID- 7501578
TI  - Chronic stable angina pectoris. Strategies for effective drug therapy.
AB  - In most patients with stable angina pectoris, severe eccentric atherosclerotic
      narrowing of coronary arteries is responsible for chest pain and myocardial
      ischemia. If myocardial infarction or death occurs, it is usually the consequence
      of a ruptured plaque. About 10% to 20% of patients with stable angina have normal
      coronary arteries, and their long-term prognosis is excellent. In patients with
      angina secondary to atherosclerotic lesions, the annual mortality rate is 1.6% to
      3.2%; prognosis is determined by systolic left ventricular function and the
      extent of coronary artery disease. Patients can be stratified into low- and high
      risk groups by medical history, left ventricular function at rest, and results of
      physical examination and stress testing. Coronary angiography should be reserved
      for high-risk patients. Risk-factor modification and appropriate use of
      antianginal drugs are successful in most patients, but those who fail to respond
      should be considered for angioplasty or coronary bypass surgery; patients with
      left main coronary artery disease or three-vessel disease and poor left
      ventricular function should be considered for coronary artery bypass surgery.

PMID- 7501579
TI  - Effect of vitamin K on oral anticoagulation.

PMID- 7501581
TI  - Superficial fungal infections. Getting rid of lesions that don't want to go away.
AB  - Systematic analysis of possible dermatophyte and candidal skin infections leads
      to an accurate diagnosis and prompt treatment with a specific regimen. The first
      steps are thorough skin examination and evaluation with a potassium hydroxide
      preparation. Tinea corporis, tinea cruris, tinea pedis, cutaneous candidiasis,
      and tinea versicolor can be treated with many topical antifungal agents, whereas
      tinea capitis requires oral griseofulvin therapy. Frequently used topical
      medications for tinea and candidal infections include clotrimazole (Lotrimin,
      Mycelex), econazole nitrate (Spectazole), ketoconazole (Nizoral), miconazole
      nitrate (Monistat-Derm, Micatin), oxiconazole nitrate (Oxistat), and ciclopirox
      olamine (Loprox). Topical selenium sulfide lotion can also be used for tinea
      versicolor, which is often a recalcitrant problem.

PMID- 7501580
TI  - Nonmelanoma skin cancer. Risks, treatment options, and tips on prevention.
AB  - The incidence of nonmelanoma skin cancer is rapidly increasing. With early
      diagnosis and treatment, almost all basal cell and squamous cell carcinomas can
      be cured. Premalignant actinic keratoses are treated with cryosurgery; the CO2
      laser is the treatment of choice for actinic cheilitis. Generally, nonmelanoma
      skin cancer can be effectively treated with excision, electrodesiccation and
      curettage, cryosurgery, or radiation therapy; 5-year cure rates are over 90%.
      Large, locally recurrent, and aggressive lesions, as well as lesions located in
      the central face, are best managed with Mohs' surgery; 5-year cure rates as high
      as 99% have been reported. Patient education about the dangers of sun exposure
      and tanning salons can potentially reduce the incidence of nonmelanoma skin
      cancer. The use of sunscreens starting early in life should be stressed.

PMID- 7501582
TI  - Diaper dermatitis. How to treat and prevent.
AB  - Dampness, maceration, fecal enzymes, chemicals, and other irritants lead to
      diaper dermatitis in infants. Most cases can be cleared with frequent diaper
      changes, use of superabsorbent disposable diapers (which contain gelling material
      in their core), and a low-potency topical corticosteroid. If the eruption lasts
      for more than 3 days or classic erythematous satellite lesions are present,
      addition of an antifungal agent should help resolve the condition. Recalcitrant
      or clinically atypical eruptions may signify rarer disorders, such as psoriasis,
      Langerhans' cell histiocytosis, Leiner's disease, or acrodermatitis
      enteropathica. Patients with these conditions should be referred to a
      dermatologist, if possible, for further evaluation and treatment.

PMID- 7501583
TI  - Pediculosis and scabies. What to look for in patients who are crawling with
      clues.
AB  - Lice and mites are highly contagious obligate parasites of humans and are spread
      by close, direct contact. Head, body, and pubic lice produce severely pruritic
      eruptions in their respective locations. Diagnosis is readily made by finding
      lice or nits on hair shafts, except in the case of body lice, which are found on
      the seams of clothing. Scabies often presents as a more generalized pruritic
      rash. Diagnosis is confirmed by finding the mite in a characteristic skin burrow.
      Crusted (Norwegian) scabies, a rare variant consisting of infestation by
      thousands of mites, occurs in patients with neurologic or immunodeficiency
      disorders. Secondary bacterial infections and eczematous changes may complicate
      both pediculosis and scabies. Infestations are easily treated with use of an
      appropriate pediculicide or scabicide and environmental-control measures.

PMID- 7501584
TI  - Effect of selection for high or low incidence of tibial dyschondroplasia for
      seven generations on live performance.
AB  - An experiment was conducted to determine the effect of divergent selection for
      tibial dyschondroplasia (TD) on live performance of broilers. Broilers used in
      the experiment were produced from the parental lines selected for high (H) and
      low (L) incidence of TD and a randombred control (C) line. Diallel crosses were
      made between H and L lines. The offspring produced were HH, HL, LH, LL, and CC,
      where the first letter refers to sire line and the second letter refers to dam
      line. Body weights, average daily body weight gains, and exponential growth rates
      were determined at weekly intervals. The incidence of TD was recorded at 4 and 7
      wk of age. There was no difference among body weights of lines up to 5 wk of age.
      Sire lines influenced body weights of birds from 5 to 7 wk of age. A significant
      interaction between sire and dam lines for body weight was the result of
      decreased body weights of birds in the HH line from 5 to 6 wk of age. There was a
      similar interaction for body weight gain, which resulted in a slower growth rate
      of birds in the HH line from 3 to 5 wk of age. Tibial dyschondroplasia incidence
      was 84.1 and 92.0% in the HH line, 5.6 and 5.4% in the LL line, and 7.0 and 13.2%
      in the CC line at 4 and 7 wk of age, respectively. It was suggested that genetic
      predisposition for TD was independent of body weight.

PMID- 7501585
TI  - In vitro fructooligosaccharide utilization and inhibition of Salmonella spp. by
      selected bacteria.
AB  - In vitro experiments were conducted to determine: 1) inhibitory capacities of
      potential direct-fed microbial bacteria against Salmonella serotypes; and 2) the
      ability of Bifidobacterium bifidum, Enterococcus faecium, Lactobacillus casei,
      Lactococcus lactis, Pediococcus sp., and Salmonella spp. to grow in media
      containing fructooligosaccharides (FOS-50 or FOS pure formulation) as the only
      carbohydrate source. Thirteen bacteria (two strains of Bacillus coagulans,
      Bacillus licheniformis, Bacillus subtilis, B. bifidum, E. faecium, two strains of
      Lactobacillus acidophilus, L. casei, Pediococcus sp., Propionibacterium
      acidopropionici, P. jensenii, and Propionibacterium sp.) were tested for
      inhibition of six Salmonella serotypes (S. california, S. enteritidis, S.
      heidelberg, S. mission, S. senftenberg, and S. typhimurium) using a spot-the-lawn
      technique. Bifidobacterium bifidum, E. faecium, all lactobacilli, and Pediococcus
      sp. clearly inhibited growth of all Salmonella serotypes. In the growth
      experiments, E. faecium, L. lactis, and Pediococcus sp. grew in media with either
      FOS-50 or the pure formulation of FOS as the sole carbohydrate source. All tested
      Salmonella serotypes utilized FOS-50 for growth; however growth varied among the
      serotypes. In contrast, none of the Salmonella serotypes grew in media containing
      the pure formulation of FOS as the only carbohydrate source.

PMID- 7501586
TI  - Effects of cage density on fear-related behavioral response and activity of
      layers.
AB  - Two experiments were conducted to study the effects of cage density on fear
      related behavioral response and activity of White Leghorn layers. In Experiment
      1, 20-wk old pullets were placed into 30.5 x 50.8 cm cages at the rate of one,
      two, three, and four birds per cage for Treatments 1, 2, 3, and 4, respectively.
      In Experiment 2, birds were placed into cages (30.5 x 50.8 cm) at the rate of
      one, two, three, four, three, two, and three birds per cage for Treatments 1, 2,
      3, 4, 5, 6, and 7, respectively, at 20 wk of age. At 28 wk of age, one bird was
      removed from each cage in Treatment 5, and one bird was added to each cage in
      Treatments 6 and 7. Fear-related behavioral response of the birds, as determined
      by the duration of induced tonic immobility (TI), and bird activity, as
      determined by the head movement (HM) count, were measured at 52 wk of age in
      Experiment 1, and at 29, 36, and 52 wk of age in Experiment 2. Increasing cage
      density had no effect on fear-related response of the birds in both experiments.
      Cage density effect on bird activity was not consistent. In Experiment 1, HM
      count was not affected by cage density, whereas in Experiment 2, pullets in the
      multiple-bird cage had a lower (P < or = .05) HM count (three-period average)
      than the birds housed individually. There was no correlation between the duration
      of induced TI and HM count in both experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501587
TI  - The effect of fumonisin B1 on isolated chondrocytes and on bone formation.
AB  - Toxic effects of fumonisin B1 (FB1) were observed with cultured chondrocytes
      isolated from epiphyseal growth plates and with growing broiler chicks. Viability
      of chondrocytes was reduced after 48 h exposure to FB1, and half lethal
      concentration of FB1 was estimated to be greater than 250 microM. Increase in
      cell size was inhibited by as low as 25 microM FB1. Dietary inclusion of
      fumonisins (55 and 110 ppm) caused a reduction in body weight, increase in liver
      weight, and decrease in feed efficiency (P < .05). However, diarrhea and bone
      malformation were not observed. It is concluded that fumonisin by itself is not
      sufficient to cause skeletal problems in poultry.

PMID- 7501588
TI  - Safety of 25-hydroxycholecalciferol as a source of cholecalciferol in poultry
      rations.
AB  - We conducted two safety studies of 25-hydroxycholecalciferol [25(OH)D3] in
      poultry broilers at levels ranging from 1 to 200 times those commonly used for
      cholecalciferol (vitamin D3) supplementation in the industry. In the first
      experiment, 1-d-old male and female broiler chickens were fed commercial diets
      containing either vitamin D3 or 25(OH)D3 at concentrations of 69, 207, and 690
      micrograms of 25(OH)D3/kg of feed. The second experiment compared effects of
      25(OH)D3 and vitamin D3 on performance and survival of broilers at levels ranging
      from 1 to 200 times the basal level of 69 micrograms/kg feed. When 25(OH)D3 was
      fed in equal amounts (wt/wt) to vitamin D3, there was an increase in body weight
      and a decrease (improvement) in adjusted feed efficiency in both experiments, but
      the changes were significant only in the first experiment. In the first
      experiment, serum 25(OH)D3 concentrations increased from 13.3 +/- 4.3 to 42.5 +/-
      18 ng/mL in birds fed vitamin D3 or 25(OH)D3, respectively, and rose to 246 +/-
      38 ng/mL in birds fed the highest level of 25(OH)D3. Tissue 25(OH)D3
      concentrations were much lower than serum concentrations and were highly
      correlated to the latter, regardless of dietary treatment. In Experiment 2, there
      was some evidence of renal calcification in birds fed 25(OH)D3 at 10 times the
      basal level, whereas dietary levels of vitamin D3 of 50 times the basal level
      were required to show some evidence of renal calcification. On the basis of both
      renal calcification and body weight, the present studies would suggest that
      25(OH)D3 is 5 to 10 times more toxic than vitamin D3.

PMID- 7501589
TI  - The folic acid requirements of starting broiler chicks fed diets based on
      practical ingredients. 1. Interrelationships with dietary choline.
AB  - Five experiments were conducted to evaluate the effect of dietary supplemental
      folic acid in starting broiler chick diets. In the first two experiments, basal
      diets based on corn and soybean meal contained 10 micrograms/kg vitamin B12 but
      no supplemental methionine or choline. Chicks showed curvilinear responses to
      folic acid supplementation with maximum growth and feed efficiencies from 1.45
      mg/kg diet. The liver folic acid response was also curvilinear but reached a
      plateau at 1.70 mg folic acid/kg diet. The basal diet for three additional
      experiments contained soybean meal that had been washed with methanol to remove
      most of the choline. The basal diet contained only 750 mg/kg choline. Chicks
      exhibited a larger growth response to folic acid at low choline levels as
      evidenced by a significant folic acid by choline interaction. Choline and folic
      acid both increased tibia length and width. Folic acid supplementation increased
      but then decreased valgus deformity. Choline chloride supplementation also
      decreased the incidences of valgus and varus deformities and decreased bone ash,
      but increased the incidence of tibial dyschondroplasia. It is concluded that
      chicks fed practical ingredient-based diets require 1.3 mg folic acid/kg diet
      with low levels of choline, but only 1.2 mg folic acid/kg when choline is offered
      near the NRC recommended level of 1,300 mg/kg of choline.

PMID- 7501591
TI  - Effect of dietary fatty acids on antibody production and fatty acid composition
      of lymphoid organs in broiler chicks.
AB  - This study examined the effect of increasing amounts of dietary polyunsaturated
      fatty acids on antibody production in vivo and fatty acid composition of plasma
      and lymphoid tissues in the broiler. Chicks were fed four diets containing 12%
      added fat made up of different proportions of palm oil and soybean oil and
      immunized against bovine serum albumin at 14 to 16 d of age. Blood samples were
      taken every 4 to 5 d for 30 d; then the chicks were killed and liver, spleen,
      thymus, bursa of Fabricius, and bone marrow were sampled. Fatty acid composition
      in serum and tissues reflected the composition of the diets, although amounts of
      saturated fatty acids were tissue-specific. Arachidonic acid concentration was
      not changed by dietary fatty acid content. Antibody production developed more
      rapidly, reached a higher level, and was more persistent in the chicks fed lower
      levels of linoleic acid. A quadratic relationship was found between tissue
      linoleic acid or total polyunsaturated fatty acid concentrations and antibody
      production at 11 and 14 d after challenge. No correlation was found with
      arachidonic acid. It is concluded that dietary fatty acid composition can
      influence immune response in broilers.

PMID- 7501590
TI  - The folic acid requirements of starting broiler chicks fed diets based on
      practical ingredients. 2. Interrelationships with dietary methionine.
AB  - Two experiments were conducted to determine the effects of dietary supplemental
      folic acid and methionine on the performance of starting broiler chicks for 18 d.
      Four levels of dietary folic acid (.24, .54, 1.14, and 2.34 mg/kg) and four
      levels of dietary methionine (.45, .53, .61, and .69%) were fed in a factorial
      design. There were three replicates of eight chicks each per each treatment. The
      basal diet was based on corn, isolated soybean protein, meat and bone meal, and
      fish meal. It contained adequate amounts of all nutrients except methionine and
      folic acid. Increased growth was observed in chicks fed the basal diet
      supplemented with either folic acid or methionine. Total dietary folic acid and
      methionine plus cysteine requirements for maximum growth were estimated to be
      1.80 mg/kg and .85% in Experiment 1 and 1.47 mg/kg and .87% in Experiment 2,
      respectively. There were interactions between dietary folic acid and methionine
      on weight gain in both experiments. Chicks fed the diet containing 2.34 mg folic
      acid/kg tended to have depressed growth, as in previous experiments. There was a
      significant linear feed conversion response to folic acid in Experiment 1 and to
      methionine in Experiment 2. There were both linear and quadratic liver folic acid
      responses to dietary folic acid in both experiments. There was no indication that
      dietary methionine had any effect on liver folic acid content. No differences in
      bone ash, hemoglobin, hematocrit, or incidence of tibial dyschondroplasia were
      detected due to methionine or folic acid supplementation.

PMID- 7501593
TI  - Removal of the alpha-galactosides of sucrose from soybean meal using either
      ethanol extraction or exogenous alpha-galactosidase and broiler performance.
AB  - Two studies using broiler chicks and one using adult White Leghorn roosters were
      conducted to determine the influence of stachyose and raffinose (alpha
      galactosides of sucrose) present in soybean meal (SBM) on the nutritional value
      of the meal. In Experiment 1, the addition of four levels (0, .05, .10, or .20
      g/kg) of alpha-galactosidase with and without 1 g/kg of invertase to a corn-SBM
      diet had no effect on weight gain, feed efficiency, protein digestibility, or the
      digestible energy value of the feed when fed to broiler chicks. However, both
      enzymes decreased (P < .001) dietary AMEn. In Experiment 2, ethanol extraction
      and incubation of SBM with alpha-galactosidase decreased the concentrations of
      the alpha-galactosides of sucrose in SBM from 6.59 to .81 and 1.43%,
      respectively. However, when broiler chicks were fed semi-purified diets
      containing SBM, ethanol-extracted SBM, water-incubated SBM, or water plus alpha
      galactosidase-incubated SBM, no improvements in weight gain, feed efficiency, or
      apparent protein digestibility were observed. There was also no improvement in
      TMEn when the above meals were precision fed to adult White Leghorn roosters
      (Experiment 3). These results indicate that the removal of up to approximately
      90% of the alpha-galactosides of sucrose has no beneficial effect on the
      nutritional value of SBM for chickens.

PMID- 7501592
TI  - Effect of early nutrient restriction on broiler chickens. 2. Performance and
      digestive enzyme activities.
AB  - An experiment was conducted to determine the effect of two early nutrient
      restriction programs on performance, selected characteristics of the
      gastrointestinal tract (GIT), and activities of digestive enzymes of broiler
      chickens. Three hundred and sixty male broiler (Ross x Ross) chicks kept in floor
      pens were assigned to three groups. The control group (C) was given ad libitum
      access to feed from 1 to 48 d of age. Another group was restricted from 11 to 14
      d (R4) of age to an energy intake of .74 x BW.67 kcal ME/d, and a third group was
      restricted from 7 to 14 d (R7) of age to an energy intake of 1.5 x BW.67 kcal
      ME/d. Then, both restricted groups were given ad libitum access to feed through
      48 d. Body weight and feed intake were determined weekly and selected carcass
      characteristics were measured at 48 d of age. Broilers also were sampled at 7,
      14, 21, and 42 d of age to obtain data on components of the GIT (proventriculus,
      gizzard, pancreas, and small intestine) and activities of selected digestive
      enzymes. Feed-restricted groups were lighter in body weight (P < .01) at 14 and
      48 d of age than the C group but were superior in overall feed efficiency. No
      treatment effects were observed for percentage yields of breast meat and
      abdominal fat pad. Absolute weights of GIT components were significantly reduced
      at 14 d of age by feed restriction. However, GIT components increased in weight
      more quickly after refeeding than did the whole body. Restricted groups had
      reduced (P < .01) specific activities of jejunal alkaline phosphatase and
      pancreatic trypsin, amylase, and lipase as compared with the C group at 14 d of
      age but not at 21 and 42 d of age. Relative activities for jejunal maltase and
      sucrase were greater (P < .01) at 21 d of age in the R4 and R7 groups than in the
      C group. The present data show that feed restriction results in transient changes
      in organs and activities of digestive enzymes, suggesting a functional adaptation
      to feed restriction.

PMID- 7501594
TI  - Effects of dietary calcium and 1,25-dihydroxycholecalciferol on the development
      of tibial dyschondroplasia in broilers during the starter and grower periods.
AB  - Two experiments were conducted to determine whether dietary 1,25
      dihydroxycholecalciferol [1,25-(OH)2D3] can prevent tibial dyschondroplasia in
      broiler chickens throughout the growing period when withdrawn from the grower
      diet. The birds were reared in floor pens with pine shavings to 6 wk in
      Experiment 1 and 5 wk of age in Experiment 2. Calcium was fed at .65 or 1.00% and
      1,25-(OH)2D3 was fed at 0 or 5 micrograms/kg to 3 wk of age. Half the birds
      consuming 1,25-(OH)2D3 were then fed 0 microgram/kg until the end of the
      experiments. The higher level of calcium decreased the incidences of tibial
      dyschondroplasia and severe lesions and increased bone ash. Dietary 1,25-(OH)2D3
      increased bone ash at both levels of calcium at 3 wk and the end of the
      experiments when supplemented for the duration of the studies. When 1,25-(OH)2D3
      was fed, tibial dyschondroplasia was reduced in Experiment 2 only at 3 wk. Tibial
      dyschondroplasia was decreased at 5 wk in Experiment 2 when .65% calcium was fed
      with or without 1,25-(OH)2D3 from 3 to 5 wk of age. There were no treatment
      effects on plasma calcium, dialyzable phosphorus, or 25-hydroxycholecalciferol.
      Plasma 1,25-(OH)2D3 was decreased at 3 and 5 wk in Experiment 2 when 1.00%
      calcium was fed. The results of Experiment 2 suggest that 1,25-(OH)2D3 can
      prevent tibial dyschondroplasia caused by inadequate calcium when fed for only 3
      wk. The bone ash observed when 1.00% dietary calcium is fed is equal to that
      obtained when 5 micrograms/kg 1,25-(OH)2D3 is fed with .65% calcium for the
      entire growout period.

PMID- 7501595
TI  - Characterization of eight endogenous viral (ev) genes of meat chickens in semi
      congenic lines.
AB  - Restriction fragment length polymorphism analysis was conducted for a set of
      eight different meat chicken-derived endogenous viral genes (ev genes) of the
      avian leukosis viral (ALV) family. Each viral element was first isolated into a
      separate single-element line by selective breeding. Genomic DNA from the founder
      male for each semi-congenic, single-element line was digested with each of four
      restriction enzymes, and the resulting Southern blots were each hybridized with
      up to four probes representing different portions of the ALV retroviral genome.
      Among the eight elements, there was one that represents the broiler equivalent of
      locus ev3 of White Leghorn chickens. A second broiler element showed a SacI
      specific junction fragment similar to that of ev8. The remainder appeared to be
      different from any of the 21 ev genes previously described for White Leghorn
      chickens. Four of the eight elements examined were essentially complete, but the
      rest have sustained internal deletions.

PMID- 7501596
TI  - A restriction enzyme map of the sex-linked late-feathering locus of chickens.
AB  - A 34-kb restriction endonuclease map of the region associated with an endogenous
      virus integration site and K, the gene that confers sex-linked late-feathering
      (LF) in chickens, is presented. Hybridizations of genomic blots of DNA from early
      feathering and LF White Leghorns indicated that the region also contains
      additional repetitive elements upstream from a chicken repetitive (CR1) element.
      This extended map and the probes described should be useful in identifying the
      molecular alterations associated with this locus.

PMID- 7501597
TI  - Phospholipid degradation is induced by heat in alpha-tocopherol-enriched eggs.
AB  - A comparative study was undertaken to determine the effect of an alpha-tocopherol
      and iodine-enriched laying diet on the phospholipid profile of egg yolk. In
      addition to the comparative study between the experimental and control eggs,
      experiments were conducted to determine the effects of heating on the
      phospholipid profile and the comparative molar ratios of cholesterol and total
      phospholipid. The phospholipid composition determined for frozen egg yolk samples
      showed no differences for the major components of phosphatidylcholine and
      phosphatidylethanolamine between the control and experimental diet group. In
      control eggs, exposure to boiling water produced time-related elevations in the
      concentration of lyso-phosphatidylcholine. A similar heat-related elevation in
      lyso-phosphatidylethanolamine was observed in both groups after 10 min. A time
      shift was observed in the heat susceptibilities of the experimental diet group.
      The control egg yolks hardened more quickly when exposed to heat. The results
      suggest protection against oxidative degradation of phospholipids and possible
      inhibition of phospholipases A2 and C, which may result from the elevated level
      of alpha-tocopherol in the experimental egg yolks.

PMID- 7501598
TI  - Effect of stunning amperage on broiler breast muscle rigor development and meat
      quality.
AB  - Two experiments were conducted to determine the effects of constant amperage (as
      opposed to constant voltage) electrical stunning on broiler blood loss, post
      mortem breast muscle (Pectoralis major) rigor development, and breast meat
      quality. Broilers were individually stunned for 5 s at 0 (unstunned control
      group), 50, 100, 150, and 200 mA in Experiment 1 and at 0, 50, and 125 mA in
      Experiment 2. Breast muscle pH and R-value (ratio of adenosine to inosine
      nucleotides) were determined at 15 min and 24 h post-mortem; breast meat shear
      value and color were determined at 48 h post-mortem. Stunning amperage had no
      effect on percentage blood loss in either experiment. The most rapid post-mortem
      reactions were observed for the unstunned control group as determined by pH and R
      value at 15 min post-mortem. Birds stunned with 50 mA were intermediate with
      regard to rate of rigor development. The slowest post-mortem reactions occurred
      in broilers stunned from 100 to 200 mA. There were no differences in pH, R-value,
      or color between stunning treatments after carcasses were aged for 24 h. Stunning
      amperage did not affect Allo-Kramer shear value for breast muscles deboned at 15
      min post-mortem. In Experiment 2, 24 h aged breast meat from broilers stunned
      with 125 mA required significantly higher shear value (4.5 kg/g) than breast meat
      from broilers stunned at 0 or 50 mA (3.8 and 3.6 kg/g, respectively). Results
      indicate that stunning amperages between 0 and 200 mA had effects on the rate of
      early rigor development but there were no consistent effects on final breast meat
      quality.

PMID- 7501600
TI  - Effects of dietary alpha-linolenic acid and strain of hen on the fatty acid
      composition, storage stability, and flavor characteristics of chicken eggs.
AB  - A study was conducted to determine the effect of dietary alpha-linolenic acid on
      the fatty acid compositions of egg yolk lipids, tocopherols, and internal quality
      of raw eggs during storage and the sensory characteristics of hard-boiled eggs
      from six different laying hen strains. Laying hens (total 300 birds, 72 wk old)
      from six strains (Rhode Island Red, Barred Plymouth Rock, New Hampshire, Light
      Sussex, Brown Leghorn, and White Leghorn) were distributed in 12 floor pens (2
      pens per strain, 25 birds per pen) with male roosters. One of the pens for each
      strain was fed with tallow-based control diet and another was assigned with 3%
      alpha-linolenic acid (LNA) enriched diet with 120 U of mixed tocopherol/kg diet
      for 3 mo. Ten eggs from each pen were collected every day after 2 wk with the
      experimental diets, and stored in a cold room at 4 C up to 4 wk. Total lipids,
      fatty acid compositions, Haugh units, and tocopherols of egg yolk were determined
      once a week during the 4-wk storage periods. Sensory studies were also conducted
      using the eggs stored for 2 wk at 4 C. Dietary LNA increased the amount of n-3
      fatty acids (6.5%) in total lipid, and over 70% was C18:3n3, and the rest was
      C22:6n3 (20 to 25%) and C22:5n3 (5 to 10%). Only minor differences in fatty acids
      among strains were observed. The differences and the changes in tocopherols
      during storage periods by strain and diet appeared randomly and lacked
      consistency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501601
TI  - Evaluation of the chicken crop as a source of Salmonella contamination for
      broiler carcasses.
AB  - Much previously published research has focused on the role of cecal and
      intestinal Salmonella contamination of poultry carcasses within commercial
      processing plants. Presently, we have evaluated the persistence of experimentally
      inoculated Salmonella enteritidis in the crops and ceca of commercial broiler
      chickens during the last week of growth (Weeks 6 to 7) and the presence of crop
      and cecal Salmonella in 7-wk-old broilers in a commercial processing plant. When
      broilers were inoculated with 1 x 10(6) cfu S. enteritidis at 6 wk of age by oral
      gavage, the incidence of crop and cecal contamination was equivalent 2d after
      challenge (30%), with only 1 of 29 crops contaminated and 0 of 29 ceca
      contaminated at 7 d following challenge. When broilers were inoculated with 1 x
      10(8) cfu S. enteritidis at 6 wk of age by oral gavage, 2 d after challenge the
      crops and ceca were observed to be 57 and 67% positive for S. enteritidis,
      respectively. Seven days after inoculation with 1 x 10(8) S. enteritidis, the
      crops and ceca were 37 and 57% positive, respectively, for the challenge
      organism. At a commercial broiler processing plant, 286 of 550 crops from three
      flocks were Salmonella-positive, whereas only 73 of 500 ceca from these flocks
      were contaminated. Furthermore, data from this plant indicated that the crops
      were far more likely to rupture than ceca (86-fold) during processing, increasing
      the possibility of carcass contamination with Salmonella derived from crop
      contents. The results of these studies suggest that the crop may serve as a
      source of carcass contamination with Salmonella within some processing plants.

PMID- 7501599
TI  - Effect of electrical stunning amperage and peri-mortem struggle on broiler breast
      rigor development and meat quality.
AB  - Two experiments were conducted to determine the effects of electrical stunning
      and peri-mortem muscle activity (struggle in and around the time of slaughter) on
      post-mortem biochemical reactions in broiler breast muscle (Pectoralis major).
      Broilers were stunned with either 50 or 125 mA or were killed without stunning.
      In Experiment 1 (n = 273), broilers were either physically restrained to reduce
      struggling during slaughter or were unrestrained and allowed to struggle freely.
      Breast mean pH and R-value (ratio of adenosine to inosine nucleotides) were
      determined at 15 min and 24 h post-mortem, and Allo-Kramer shear was determined
      on 48 h post-mortem cooked meat samples from muscles excised at 15 min or 24 h.
      In Experiment 2 (n = 65), the breast muscle was unilaterally denervated by
      surgically severing the Pectoralis nerve on one side and performing a sham
      operation on the contralateral side. Results indicated that physical restraint
      resulted in higher muscle pH and lower R-values at 15 min post-mortem in the
      unstunned birds and birds stunned at 50 mA, but had no effect on breast meat from
      birds stunned at 125 mA. There were no treatment effects on meat tenderness or 24
      h post-mortem pH or R-values. Stunning amperage had no effect on denervated
      muscle pH at 15 min post-mortem, but did affect the sham-operated muscle pH and R
      values as in Experiment 1. These results indicate that the main effect of
      electrical stunning on early rigor development may be due primarily to inhibition
      of peri-mortem struggle.

PMID- 7501602
TI  - Fermentation of radiolabeled carbohydrates by a reconstructed continuous-flow
      culture effective against Salmonella in broiler chicks.
AB  - An 81-d-old continuous-flow (CF) culture of broiler cecal bacteria was maintained
      in a lactose-based broth. The culture had been previously proven effective
      against Salmonella colonization in young chicks, especially when the chicks were
      provided dietary lactose. Portions of the CF culture were batch-cultured in
      glucose- and lactose-based broths containing 14C-labeled lactose, glucose,
      galactose, or lactic acid to determine the effect of media carbohydrate on
      fermentation products. Acetic and propionic acids were the major 14C-labeled
      fermentation products. 14C-Carbohydrates were fermented to lactic acid and then
      to acetic and propionic acids. Distribution of radiolabeled fermentation products
      was effected by the broth carbohydrate and the time postinoculation.

PMID- 7501603
TI  - [New data on mineralocorticoid hormones. Physiopathological implications].
AB  - Our better understanding of the terminal steps of aldosterone production based on
      enzyme cloning has led to new clinical approaches to three aldosterone-related
      types of hypertension: mineralocorticoid excess, Liddle's disease and
      glucocorticoid-sensitive hyperaldosteronism. In all three cases, hypertension
      results from volume expansion due to increased reabsorption of sodium in the
      distal renal tube with decreased plasma renin activity and hypokaliaemia. Genetic
      testing now allows early diagnosis of these severe familial diseases and specific
      treatment. Although both glucocorticoid-sensitive hypertension and Liddle's
      disease are dominantly inherited diseases, other genes can also modulate the
      degree of volume expansion, hypokaliaemia and blood pressure levels within a
      given family. The degree of hypertension observed in a given individual results
      from the interactions between the expression of "hypertenser" and "hypotenser"
      genes. Recent progress raises the possibility that other similar genetic
      mechanisms exist in more common forms of primary hypertension. Systematic
      exploration of the renin-angiotensin-aldosterone system based on measurement of
      the renin/aldosterone ratio as proposed in the diagnosis of primary
      hyperaldosteronism will make it possible to determine whether there exists a
      relationship between these genes and the hypertension observed.

PMID- 7501604
TI  - [Conn's adenoma. Diagnostic and prognostic value of the measurement of potassium,
      renin, aldosterone levels and the aldosterone/renin ratio].
AB  - OBJECTIVES: To evaluate diagnostic criteria in primary aldosteronism, we studied
      the sensitivity and specificity of potassium, renin, aldosterone and the
      renin/aldosterone ratio in 60 patients undergoing surgery for Conn's adenoma, 50
      patients with primary hypertension and 49 normal controls. We also searched for a
      relationship between these parameters and the blood pressure outcome of surgery.
      METHODS: The diagnostic value of the tests was quantified using the Youden index
      after adjustment for receiver operating characteristic (ROC) thresholds. RESULTS:
      Potassium level in patients was lower than in controls, but in 22%, kaliemia was
      > or = 3.5 mmol/l and the threshold giving the best Youden index (0.93) was 3.9
      mmol/l. The diagnostic power of active renin was low (Youden index 0.28), but the
      Youden indexes for aldosterone level and the aldosterone/renin ratio in supine
      position were 0.68 and 0.66 respectively. After a mean follow-up of 8.7 months
      after surgery, 70% of the patients had normal or improved blood pressure levels.
      None of the biological parameters evaluated was associated with blood pressure
      outcome, but age > 55 years was related to unfavorable outcome (sensitivity and
      specificity 80 and 60%). CONCLUSION: The threshold level requiring a search for
      an adenoma should be raised. When the potassium level is < or = 3.9 mmol/l the
      aldosterone/renin ratio should be measured in supine position since it evaluates
      the dissociation between renin and aldosterone seen in primary
      hyperaldosteronism. The effect of age on the surgical result emphasizes the
      importance of early diagnosis.

PMID- 7501605
TI  - [Hyperaldosteronism sensitive to dexamethasone with adrenal adenoma. Clinical,
      biological and genetic study].
AB  - OBJECTIVES: Dexamethasone-sensitive hyperaldosteronism is associated with early
      onset hypertension and primary hyperaldosteronism. Diagnosis is difficult but can
      be improved by genetic testing for the mutant gene. METHODS: We collected the
      clinical, biological and genetic elements observed in a family with dexamethasone
      sensible hyperaldosteronism. Complete data were obtained in 5 adult subjects with
      the disease. Degree of hypertension varied, more so in the second generations as
      did hypokaliaemia and hyperaldosteronism. In affected patients, there was a 10 to
      50 fold increase in urinary 18-OH components and 18 oxocortisol. RESULTS: Single
      dose (1.5 mg) dexamethasone led to a greater than 80% drop in aldosterone levels
      in the blood and urine, confirming the abnormal effect of ACTH on
      mineralocorticoid secretion. At the dose of 1 mg/d for 10 weeks, dexamethasone
      lowered mean 24-H ambulatory arterial pressure (11.8/9.6 mmHg) and corrected for
      the hypokaliaemia (+0.54 mmol/l) and the hyperaldosteronism (mean decrease -36%
      and -75% in blood and urine respectively). An adrenal tumour was identified in
      hyperplasic glands in two subjects and a micronodular formation was identified in
      two others. The specific molecular diagnosis of the disease was done with
      Southern blotting. Among the 18 families in 3 generations, 8 carried a 11 beta
      OHase-aldosterone synthetase chimeric gene. This mutation cosegregates with
      hormonal abnormalities and confirms the autosomal dominant inheritance of the
      disease. CONCLUSION: The simplicity and rapidity of genetic testing allows early
      diagnosis of this disease among families with early onset hypertension and
      associated hyperaldosteronism with or without adrenal hyperplasia and/or a
      tumoral formation.

PMID- 7501606
TI  - [Invasive group A streptococcal infections in France].
AB  - OBJECTIVES: Following the recent report of necrosing fasciitis cases in Great
      Britain, we conducted a study of group A streptococci infections in France to
      evaluate the frequency and severity of the different clinical presentations,
      particularly necrosing fasciitis. METHODS: Thirteen hospital laboratories were
      selected because of the large number of group A streptococci blood cultures they
      observed in 1993. The microbiologists in these hospitals, in relation with
      clinicians, identified 83 patients with a group A streptococci bacteraemia
      between January 1, 1993 and June 30, 1994. RESULTS: Sixty-three percent of the
      patients had an underlying condition: 39% had a chronic general or local disease
      and 24% had severe immunodepression. The skin portal of entry was found for 70%
      of the cases. Patients were divided into 4 groups according to the clinical
      picture: there were 16 cases of streptococci shock syndrome, 13 with deep
      infections, 25 infections of soft tissue (including 3 cases of fasciitis) and 29
      cases of isolated bacteraemia. CONCLUSION: Overall, one-fourth of the patients
      died due to the streptococci infection, one-half of whom had a toxic shock
      syndrome. Mortality was correlated with age and health status, but also with the
      clinical presentation of the disease. Compared with former years, there was no
      increase in the number of group A streptococci infections, nor in the number of
      necrotizing fasciitis in France in 1993. However, streptococci shock syndrome is
      of particular importance because of its frequency and poor outcome.

PMID- 7501607
TI  - [Homozygote deficiency of thiopurine methyltransferase. A contraindication to the
      use of azathioprine in kidney transplantation].
AB  - Azathioprine-induced myelosuppression is the most important side effect observed
      in kidney transplantation. We report a case of severe neutropenia after kidney
      transplantation due to a thiopurine methyltransferase deficiency. This cause of
      azathioprine-induced myelotoxicity is rare, but its infectious consequences may
      be severe. Thiopurine methyltransferase deficiency must therefore be suspected
      when early and severe leukopenia occurs during azathioprine therapy. Erythrocyte
      thiopurine methyltransferase activity measurement confirms the diagnosis.
      Azathioprine and 6-mercaptopurine must afterwards be definitively avoided.

PMID- 7501608
TI  - [Bradycardia during treatments of weight loss].
AB  - Sinus bradycardia was observed in 10 adolescents participating in a weight loss
      diet conducted in a health centre. The precise cause was assessed. The subject's
      age ranged from 10 to 15 years and weight loss ranged from 8 to 24 kg over a
      period ranging from 8 to 23 weeks. None of the subjects had taken drugs with a
      bradycardic effect and search for toxic agents in the blood and urine was
      negative in all cases. Infection was suggested since 8 of the 10 adolescents had
      a rhinopharyngitis a few weeks before the discovery of bradycardia. This cause
      was not retained due to the lack of any signs of infection or inflammation and
      negative virus serology. Nutritional status was therefore retained as the most
      likely cause in these adolescents who were eating a diet containing < or = 1350
      kcal/day. This hypothesis was supported by the results of work reported in 1970
      showing arrhythmia in very low calorie diets. The effect is essentially related
      to the biological value of proteins in the diet, its duration and the initial
      weight of the subjects. In addition bradycardia is frequently seen in subjects
      taking hypocaloric diets or with anorexia nervosa and should be considered as an
      adaptation to hypometabolism rather than a true heart disorder. Thus the
      biological value of the proteins and the mineral status should be taken into
      consideration during the course of low calorie diets, even though bradycardia is
      frequent and does not require a specific treatment. Therefore heart rate and
      decreasing rate of weight loss should be carefully followed during the course of
      low calorie diets.

PMID- 7501609
TI  - [A new model of the sterno-thoracic retractor].
AB  - Vertical medial sternotomy is recognized as the best approach for heart surgery.
      We have modified the double valve Chevalier retractor (widely used since 1962 and
      adapted by others) to improve its performance. A new articulation on the
      retractor arms facilitates installation of extracorporeal circulation and
      epicardial electrodes without removing the device. The position of the rack-bar
      can also be modified to avoid cervical compression. In addition, the inferior
      aspect of the rack-bar has been covered with a plate to avoid catching the
      drapes.

PMID- 7501610
TI  - [Maternal serum markers of fetal trisomy 21].
AB  - Down's syndrome is the most frequent genetic disease. Each year, in France, there
      are 1,100 trisomy 21-affected newborns. this chromosomal disease is the most
      frequent cause of mental retardation raising an important public health problem.
      Prenatal diagnosis of chromosomal anomalies is based on fetal karyotyping, but
      cannot be proposed in all situations because of the cost and the risk of fetal
      death due to amniocentesis. The aim of screening is to define patients at
      increased risk for trisomy 21. Three criteria are currently used to define an at
      risk-population: maternal age, ultrasound anomalies, and maternal serum markers.
      In France, amniocentesis is proposed to patients over 38 years of age. Ultrasound
      signs for trisomy 21 are often difficult to identify at routine echography. Based
      on a prospective study of 51,048 women under 38 years of age, we observed that
      maternal serum hCG at 15 weeks can detect 59% of all trisomy 21 cases while the
      yield for amniocentesis is 6.1%.

PMID- 7501611
TI  - [Paraneoplastic peripheral neuropathy in the course of leiomyosarcoma].

PMID- 7501613
TI  - [Meningitis caused by Nocardia without brain abscess detectable by computed
      tomography].

PMID- 7501612
TI  - [Septic pyemic form of human melioidosis: a first case in the French Antilles].

PMID- 7501614
TI  - [Prevalence of hepatitis E virus antibodies in pregnant women in the Paris
      region: serological considerations].

PMID- 7501615
TI  - [Cerebral ischemic accidents in AIDS. Two new cases].

PMID- 7501616
TI  - [Ocular venous thromboses: relationship with the G1691A mutation on the gene of
      factor V].

PMID- 7501617
TI  - [Ethical reflections on HIV infection].

PMID- 7501618
TI  - [Sports, bones and hormones. Multiple interactions].
AB  - Classically, sports activities are thought to have a beneficial effect on bone
      tissues. Actually, there are many interactions between sports activities and bone
      tissue and in certain cases complex hormone disorders may develop. Recent
      progress in the evaluation of bone structure (absorptiometry) and better
      understanding of the neuroendocrine functions have improved our knowledge of
      these interactions and helped provide answers as to the true effect of sports,
      and particular high-level training, on bone tissue. Mechanical stimulation of
      bone increases the level of both cortical and cancellous bone formation. The
      mechanical effect is localized in areas under particular constraint such as the
      lower limbs in runners and the upper predominant limb in tennis players.
      Inversely, hypoestrogenism, similar to anorexia nervosa, has been observed to be
      the cause of general bone loss and increased risk of osteoporosis in certain high
      level athletes. When these two opposing phenomena occur simultaneously, there is
      generally an overall loss of cancellous bone mass while bones submitted to major
      mechanical stress may be relatively protected. Amenorrhoea, particularly in long
      distance runners, generally occurs when training exceeds 30 km per week. Menarche
      may be delayed by 1 or 2 years when training begins early and dismenorrhoea is
      seen in 50% or more of the athletes. Amenorrhoea results from a central disorder
      due to insufficient pulsatile secretion of luteo-releasing hormone and subsequent
      hypogonadism. The role of beta-endorphins or catelestrogens on hypothalamic
      receptors has been suggested as the underlying mechanism. These different
      observations help provide answers to the different problems raised when providing
      counselling and care for high level athletes.

PMID- 7501619
TI  - [Urination disorders in HIV infected patients].
AB  - OBJECTIVES: Manifestations of urological involvement, including tumour
      development, infection and impaired micturition are frequent in patients with
      acquired immunodeficiency syndrome. The frequency and consequences of dysuria
      itself are difficult to evaluate due to the concomitant effects of underlying
      infections, obstructive or neurological pathologies. METHODS: Thirty-nine HIV
      positive patients presenting impaired micturition including isolated dysuria,
      urine retention pollakiuria or urge incontinence were followed prospectively from
      February 1989 to September 1992. Each patient underwent a complete neurological
      and urological examination. Imaging included CT-scan or magnetic resonance
      imaging of the brain or spinal cord, echography of the bladder and prostate,
      intravenous pyelography or ascending and micturition urethrocystography as
      required. Urinary function tests were used to determine the cause and exact type
      of impairment to establish therapeutic protocols. RESULTS: A neurological origin
      was found in 61.5% of the cases. Cerebral toxoplasmosis and HIV encephalitis were
      the most commonly found causes. Symptomatic relief was obtained in most patients
      with bladder- sphincter active drugs. After a mean follow-up of 9 months (range 2
      24 months), long-term improvement was achieved in 57.9%. Seventeen patients (44%)
      died within a delay of 2 to 24 months (mean 8 months) after onset of dysuria.
      CONCLUSION: Signs of impaired micturition are frequently encountered in HIV
      infected patients. A full work-up is needed for diagnosis and treatment
      adaptation. Neurological disease is the most frequent underlying cause and would
      appear to be a sign of poor prognosis.

PMID- 7501620
TI  - [Breast cancer without palpable tumor revealed by microcalcifications. Prognosis
      and treatment].
AB  - OBJECTIVES: Routine screening mammography has greatly increased the number of
      breast cancers detected in the form of clumped microcalcifications without a
      palpable tumour. METHODS: From 1964 to 1989, 315 breast cancers revealed by
      microcalcifications without contralateral cancer, treated at the Institut Curie.
      Cancers were observed in 40% of the microcalcifications excised. Treatment was
      conservative in 57.5% of cases and mutilating in 42.5% of cases; these rates have
      changed only very slightly with time. Histologically, 50% of the tumours were
      intraductal cancers, 25% were microinvasive, 24% were infiltrating and 1% were
      lobular in situ carcinomas. The therapeutic indication can be defined on the
      basis of the histological result of the initial tumour excision, as the initial
      examination underestimated the lesions in only 5.6% of cases. Lymph node invasion
      was observed in 1.8% of intraductal cancers, 5.3% of microinvasive cancers and
      14.8% of invasive cancers. RESULTS: The overall survival was 99% at 5 years and
      89.9% at 10 years. The prognosis of invasive cancer was less favourable than that
      of intraductal and microinvasive cancers (p = 0.03). Survival was not influenced
      by the radical or conservative nature of treatment. The presence of lymph node
      invasion severely worsened the prognosis. The 5 year recurrence rate was 4.2% for
      intraductal, 4.6% for microinvasive and 6.1% for invasive. The incomplete nature
      of the resection increased the local recurrence rate: 11.9% at 5 years instead of
      5%. CONCLUSION: Conservative treatment of cancers revealed by microcalcifications
      without a palpable tumour therefore appears to be justified provided the lesion
      is radiologically localized, with a histologically satisfactory resection and in
      the absence of residual microcalcifications on postoperative mammography.

PMID- 7501621
TI  - [Voluntary drug poisoning cases admitted to an emergency care unit].
AB  - OBJECTIVES: The aim of this study was to ascertain the specific nature of
      voluntary drug intoxications seen in emergency wards receiving adult patients.
      METHODS: From July 1992 to June 1993, all patients presenting at the emergency
      room with voluntary drug intoxication were assessed retrospectively. There were
      727 patients (482 females and 245 males, mean age 33.3 +/- 12 years, age range 15
      92) admitted for 804 episodes of voluntary drug intoxication. RESULTS: A past
      history of psychiatric problems or drug abuse was found in 42.8 and 9.1% of the
      patients respectively. The time laps between ingestion and consultation was noted
      for 43% (5 h 30 +/- 9 h, range 15-4320 min). The drug ingested was identified in
      89% of the cases and 1.7 drugs were ingested per episode (range 1-8). Generally,
      only 1 (52%) or 2 (21%) drugs were ingested. Nonbarbituric psychotropic agents
      were ingested in 79.7% of the cases. Alcohol had also been consumed in 36.5% of
      the cases. Treatment was gastric lavage in 34.4%, activated carbon in 16.7%,
      flumazenil in 16.9%, naloxone and N-acetyl-cysteine in 3.4%. Twelve patients
      required intubation. Patients were admitted to a medical (n = 156) or psychiatric
      (n = 67) ward or an intensive care unit (n = 61). Nearly 25% of the patients left
      hospital either against medical advice or left without notice. CONCLUSION:
      Voluntary drug intoxications seen in emergency rooms require care by a well
      coordinated team of clinicians and psychiatrists.

PMID- 7501622
TI  - [Fahr syndrome and dysparathyroidism. 3 cases].
AB  - Fahr's disease associates various degrees of neuropsychological impairment and
      calcium deposits in the basal ganglia. We report 3 cases. The first case was a 54
      year-old man with hemichorea of one-year duration. Laboratory results
      demonstrated idiopathic hypoparathyroidism. In the second case, a 23-year-old man
      treated for epilepsia for 8 years was hospitalized for subintrant episodes and
      hemichorea. Dysmorphism and laboratory results led to the diagnosis of pseudo
      hypothyroidism. The third case was a 62-year-old woman with generalized seizures
      of epilepsia and dementia of two-month duration. Physical examination revealed
      extra-pyramidal rigidity. Hyperparathyroidism due to an adenoma was confirmed
      histologically. In all three patients, correction of phosphocalcium levels led to
      clinical improvement, particularly with disappearance of the epileptic seizures
      and abnormal movements. Clinical expression of Fahr's syndrome varies greatly.
      Symptoms include psychiatric disorders, epileptic seizures, extra-pyramidal
      syndrome and various neurological conditions. Diagnosis requires CT brain scan
      which identifies calcium deposits in the basal ganglia. The main cause is
      hypoparathyroidism, whether primary or post-operative. Cases due to other causes
      of dysparathyroidism are rare. The pathophysiology of this condition remains
      unknown and results of treatment are often unsatisfactory. Since correcting the
      impaired calcium phosphorus metabolism often leads to considerable improvement,
      it is essential to systematically search for dysparathyroidism in patients
      presenting with neuropsychologic manifestations associated with calcifications of
      the basal ganglia.

PMID- 7501623
TI  - [Partial properdin deficiency revealed by a septicemia caused by Neisseria
      meningitidis].
AB  - Properdin is one of the regulatory proteins of the alternative pathway of the
      complement system. Human properdin deficiency is an X-linked disorder strongly
      predisposing to meningococcal disease. Total deficiency (type I), partial
      deficiency (type II), and deficiency due to a dysfunctional molecule (type III)
      can be differentiated immunochemically. Four males in a family showed a selective
      partial deficiency of properdin. These individuals had 10% of normal properdin
      concentration in plasma, as measured by ELISA, while the other complement
      components were normal. Two of the properdin-deficient individuals in two
      generations had meningococcal infections. Two were clinically healthy at the time
      of investigation. Measurement of plasma levels of properdin has to be performed
      in the case of Neisseria meningitidis, especially where there is a previous
      history of severe bacterial infections in the same family as measurement of CH50
      activity is ineffective for screening properdin deficiency.

PMID- 7501624
TI  - [Percutaneous cementoplasty for malignant osteolysis of the acetabulum].
AB  - The development of malignant lesions in the acetabulum can lead to painful and
      disabling bone destruction. In carefully selected patients where the cortical
      still provides a sufficient barrier protecting the joint, percutaneous injection
      of ciment (10-15 cc) can be a successful mean of countering both pain and
      functional impairment. This easy-to-perform technique requires only local
      anaesthesia and can be highly cost-effective. The antalgic effect is rapid. Most
      patients are able to walk again within 1 to 5 days (an effect which is
      particularly spectacular in bedridden subjects) probably due to the reduced pain
      and to better distribution of the mechanical forces. Hospitalization is usually
      shortened. In our experience with 18 patients, clinical improvement has been
      maintained for up to 18 months (mean follow-up 7 months) if the osteolytic
      process remains under control. Secondary effects are not rare but usually
      temporary. Recurrent pain, fever and/or inflammatory processes have been observed
      and usually resolve within 1 to 4 days. Intra-articular leakage can be avoided by
      careful patient selection. In association with radiotherapy, percutaneous
      injection of ciment appears to be an useful alternative to surgery for patients
      with destructive malignant lesions of the acetabulum, particularly in those with
      a poor clinical status and a short life expectancy. This technique has already
      been shown to be effective in lesions of the vertebral bodies. Several teams have
      made further attempts in other localizations.

PMID- 7501625
TI  - [Emergency medical treatment of portal hypertension].
AB  - The main aetiology of acute gastrointestinal haemorrhage in cirrhotic patients is
      variceal bleeding. Prognosis is determined by early or late rebleeding rates and
      the severity of underlying liver disease, mostly estimated by Child Pugh score.
      Diagnosis and therapy of variceal bleeding is currently based on endoscopic
      sclerotherapy and more recently on banding ligation. However, the management of
      acute variceal bleeding remains controversial and vasoactive drugs are an
      alternative treatment. At present, most of these studies showed encouraging but
      conflicting results. These trials show that the cyclic octapeptide analogue
      (octreotide) of somatostatin or the triglycyl analogue (terlipressin) of
      vasopressin are safer and more effective than their natural drugs respectively.
      Clinically, drug choice depends on four factors: -results of trials comparing
      vasoactive treatment to classical sclerotherapy: comparison of these two kinds of
      treatment show similar results concerning haemostatic rate as well as mortality
      especially for somatostatin or its synthetic analogue; -results of trials
      comparing synthetic analogue of vasopressin to cyclic analogue of somatostatin in
      variceal bleeding: current study designs demonstrate an arithmetic difference (p
      = 0.06) with a better early haemostatic rate after octreotide associated with
      comparable final haemostasis (after 24 hours) and mortality; -results of
      combination of both treatments (i.e. sclerotherapy associated with vasoactive
      drug versus sclerotherapy): such association decreases variceal rebleeding
      without improvement of survival rate; -and finally, importance of adverse drug
      effects on hepatic and renal functions: few studies show scanty and conflicting
      adverse drug effect especially on free water clearance which must be studied by
      further clinical trials to confirm their benefit in emergency management of
      variceal bleeding.

PMID- 7501626
TI  - [Muscle sarcoma of the sacrum revealed by sciatica].

PMID- 7501627
TI  - [Prostatic tuberculous abscess in AIDS. 2 cases].

PMID- 7501628
TI  - [Cordocentesis: effect on umbilical and medial cerebral Doppler flow rates].

PMID- 7501629
TI  - [Splenic hemangiopericytoma].

PMID- 7501630
TI  - [Edema of the lower limbs revealing trichinosis identified by duodenal biopsy].

PMID- 7501631
TI  - [Emery-Dreifuss disease with dominant autosomal transmission. A new family].

PMID- 7501632
TI  - An enzyme-linked immunosorbent assay with whole trophozoites of Toxoplasma gondii
      from serum-free tissue culture for detection of specific antibodies.
AB  - This paper describes a new procedure of preparation of the antigen for an enzyme
      linked immunosorbent assay (ELISA) for detection of antibodies against Toxoplasma
      gondii. To examine the reliability of this ELISA using whole trophozoites
      produced in a serum-free tissue culture as an antigen, 221 sera were tested
      comparatively in the new system (TTE, total trophozoites ELISA), in the indirect
      fluorescent antibody test (IFAT), and in a commercially available ELISA using
      sonicated trophozoites as an antigen (STE, sonicated trophozoites ELISA). The
      ELISA with antigen lysate showed a good correlation with the IFAT; however, false
      negative results were sometimes obtained. The TTE was performed with all sera in
      two modifications: one test with an anti-IgG conjugate (G-TTE) and the other with
      an anti-Ig-G, -M, -A conjugate (GMA-TTE). In none of these TTE modifications were
      insensitivities observed; however, the G-TTE seems to offer a clearer
      differentiation between specifically reactive and nonreactive findings. The
      present study shows that the ELISA with whole trophozoites produced in serum-free
      tissue culture might be used as an alternative test to the IFAT. This test
      combines the advantages of the ELISA system with the sensitivity and specificity
      of the IFAT.

PMID- 7501634
TI  - Prevention of clinical trichostrongylidosis in calves by strategic feeding with
      the predacious fungus Duddingtonia flagrans.
AB  - The present investigation showed that strategic feeding of first-season calves
      with the microfungus Duddingtonia flagrans through the initial 3 months of the
      grazing season could prevent severe clinical trichostrongylidosis in the late
      summer. The successful prevention of disease was particularly noteworthy in view
      of the high stocking rate practiced on this permanent pasture, which was widely
      contaminated with a range of gastrointestinal nematodes. The results showed that
      larval populations of Ostertagia and Cooperia were significantly reduced on the
      pasture grazed by the fungus-treated calves. Numbers of Nematodirus seemed less
      affected. The present paper discusses the complexity of fungus-nematode
      interactions in dung pats under natural conditions.

PMID- 7501633
TI  - Genetic comparison of Neospora caninum with Toxoplasma and Sarcocystis by random
      amplified polymorphic DNA-polymerase chain reaction.
AB  - To determine the relationship of Neospora caninum to protozoa classified in the
      family Sarcocystidae of the phylum Apicomplexa, the genomes of N. caninum, three
      Toxoplasma gondii strains (RHa, CEP, TPR) and three Sarcocystis species (S.
      tenella, S. muris, S. gigantea) that were thought to be closely related coccidia
      were compared by the random amplified polymorphic DNA (RAPD) polymerase chain
      reaction (PCR) technique. The genomic DNAs were amplified by the use of seven 10
      mer arbitrary sequence primers to generate polymorphic DNA. Significant DNA
      polymorphisms were observed among Neospora, Toxoplasma and Sarcocystis. It
      appears that one primer tested may have value in a diagnostic RAPD-PCR to
      differentiate T. gondii from other closely related protozoa. The high level of
      genetic divergence of N. caninum from T. gondii strains and several Sarcocystis
      species observed in this study is consistent with the hypothesis that N. caninum
      is indeed an independent species of protozoan parasite. As compared with the
      Sarcocystis species tested, a closer genetic relationship of N. caninum to T.
      gondii was not observed. By contrast, a closer genetic relationship of S. muris
      to T. gondii was revealed in this study.

PMID- 7501635
TI  - Immunoelectron microscopical localization of a circulating antigen in the
      excretory system of Schistosoma mansoni. Ultrastructural localization studies of
      the excretory system of S. mansoni.
AB  - In this study the excretory system of Schistosoma mansoni was ultrastructurally
      examined with a recently described monoclonal antibody (mAb) against a
      circulating antigen. In previous studies this mAb was found to have affinity for
      the excretory system. Strong immunoreactivity was found on the flagella of the
      flame cells and of the collecting ducts throughout the worm. The eggshell and the
      space between the miracidium and the eggshell showed strong reactivity with a
      declining gradient towards the exterior, suggesting a secretion process. In
      cercariae, immunoreactivity was restricted to the tegument, whereas in
      schistosomula the labeling pattern resembled that of the adult worm,
      demonstrating positive reactivity of the flame cells and no immunostaining of the
      tegument. This stage-dependent differential expression of different antigens in
      the excretory system and in the tegument could suggest a maturation process of
      the excretory system.

PMID- 7501636
TI  - Cloning and immunological characterisation of Echinococcus granulosus ferritin.
AB  - A cDNA clone of Echinococcus granulosus has been isolated from an expression
      library screened with sera from cystic echinococcosis patients. The deduced amino
      acid sequence shows 56% homology to the heavy chain of human ferritin. E.
      granulosus ferritin contains 173 amino acid residues and has a calculated
      molecular weight of 19830 Da and a statistical isoelectric point of 7.6.
      Functionally important amino acid residues of the ferroxidase centre are
      conserved in comparison with other ferritins. In vitro-translated E. granulosus
      ferritin was tested for its diagnostic potential by immunoprecipitation. The
      antigenic reactivity exhibited a good potential for the further development of E.
      granulosus ferritin as an immunodiagnostic tool for human hydatidosis.

PMID- 7501638
TI  - Ionic composition of the liver fluke Fasciola hepatica from different mammalian
      hosts and comparison with host bile.
AB  - A qualitative analysis of the cationic profile of bovine and ovine biles and of
      bovine, ovine and rat liver flukes has been carried out by DC arc emission
      spectrography. A quantitative assessment of the concentrations of Na+, K+, Ca2+
      and Mg2+ ions in bovine, ovine and rat flukes has been determined by atomic
      absorption spectrophotometry. The levels of these ions in bovine and ovine bile
      samples have also been assessed and compared with those of Hedon-Heig saline. The
      ionic composition of the two biles is similar and the concentration of each ion
      is greater than that in Hedon-Heig saline. Despite the similarity in biles, ion
      levels in bovine flukes are generally higher than those in ovine flukes. Ion
      levels in rat flukes are different again but show closer similarity to those in
      bovine, not ovine, flukes. The results are discussed in relation to the proposed
      operation of the osmoregulatory system in the fluke.

PMID- 7501637
TI  - Comparison of the patterns of codon usage and bias between Brugia, Echinococcus,
      Onchocerca and Schistosoma species.
AB  - Patterns of codon usage and bias were compared among taxa of the genera Brugia,
      Echinococcus, Onchocerca and Schistosoma by metric multidimensional scaling and
      three commonly used indices of bias: Nc, GC3S and B. The overall codon usage for
      each taxon was compared, as was the codon usage for each individual gene within
      the taxa. Differences in the patterns of codon usage observed between taxa were
      dependent on the overall base composition of the genes analysed. The codon usage
      of Echinococcus was distinct from that of the other taxa. Furthermore, the
      pattern of codon usage detected by the average codon usage summed across all
      genes for each taxon was not shown by all genes from that taxon.

PMID- 7501639
TI  - Cell-adhesion molecules expressed by activated eosinophils in Onchocerca volvulus
      infection.
AB  - Cell-adhesion receptors mediate the interaction between host effector cells and
      cellular or multicellular targets, including opsonized parasites. Our recent
      finding of a deposition of plasma proteins, including fibronectin, on the surface
      of infective larvae of the helminthic parasite Onchocerca volvulus led us to
      investigate the possible expression of cell-adhesion molecules (CAM),
      particularly fibronectin receptors, on eosinophilic granulocytes from persons
      infected with O. volvulus. Immunofluorescence analyses showed that freshly
      isolated eosinophils strongly expressed the beta 2-integrin CR3 and exhibited to
      a lower degree CR4 and the integrin-associated carbohydrate determinant Le(x), as
      well as antigen p24 (CD9). Eosinophils exposed to the eosinophil-active cytokines
      recombinant human interleukin 3 (rhIL-3) and granulocyte/macrophage colony
      stimulating factor (rhGM-CSF) in addition to CR3, CR4, and CD9 expressed the beta
      1-integrins VLA-4 and to a lesser extent VL-5 (both fibronectin receptors) as
      well as the intercellular adhesion molecule ICAM-1. Low-level expression of these
      adhesins was also observed on eosinophils cultured in the presence of these
      interleukins on confluent fibroblasts. The presence of VLA-4 as well as VLA-5 on
      activated eosinophils was confirmed by demonstration of the formation of immune
      rosettes using antibody-coated microspheres and by their attachment to
      fibronectin-coated surfaces. These results indicate the possibility of an
      involvement of previously unidentified antibody- and complement-independent
      mechanisms in cellular interactions with the parasite O. volvulus.

PMID- 7501642
TI  - Ribosomes of Leishmania are a target for the aminoglycosides.
AB  - Ribosomes of Leishmania, a parasitic protozoan (member of the order of
      Kinetoplastidae), were purified on a sucrose density gradient. Two different
      types of ribosomes were isolated from the promastigotes: cytoplasmic (88S and 91S
      from L. tropica and L. donovani, respectively) and mitochondrial (75S in both
      species). Both types of ribosome dissociated into their subunits at low Mg2+
      concentration (1-2 mM) as follows: 67S and 49S for the 91S cytoplasmic ribosomes
      of L. donovani and 61S and 43S for the 88S cytoplasmic ribosome of L. tropica;
      55S and 34S for L. tropica and 60S and 39S for L. donovani mitochondrial
      ribosomes, respectively. Paromomycin (aminosidine), an aminoglycoside
      aminocyclitol antibiotic, interacted with the ribosomes to promote the
      association of the subunits. Under similar experimental conditions, spermidine
      and pentamidine were inactive.

PMID- 7501641
TI  - Flagellum-mediated adhesion of Trypanosoma congolense to bovine aorta endothelial
      cells.
AB  - We studied the interaction between Trypanosoma congolense and bovine aorta
      endothelial (BAE) cell monolayers. Our findings suggest that trypanosomes adhere
      predominantly to the flattened, peripheral cell surface domains as well as to
      filamentous endothelial outgrowths that are present during in vitro cultivation
      in non-confluent monolayers. Adhesion is mediated exclusively by the flagellum in
      a distinct geometrical order with respect to the flagellar cytoskeleton. Thus, it
      is possible to define exactly the trypanosomal cell surface domain involved in
      the attachment process. After 24-48 h of cultivation on monolayers, trypanosomes
      start to develop short, filopodia-like flagellar protrusions, which serve as
      additional elements in assisting parasite attachment. Small filaments (3-5 nm)
      also serve as cross-links between flagellar and endothelial cell surface
      membranes. Lectin-gold labeling shows that these cross-links contain sialic acid
      residues. In vitro assays confirm that sialic acid is involved in the adhesion
      process, whereas the extracellular matrix (ECM) proteins fibronectin, collagen,
      laminin and vitronectin are not. The presence of T. congolense exhibits a
      mitogenic effect on BAE cells.

PMID- 7501640
TI  - Ultrastructure study of the excretory system and the genital primordium of the
      infective stage of Onchocerca volvulus (Nematoda:Filarioidea).
AB  - The electron microscopic investigation of the anterior part of the infective
      third-stage juvenile of Onchocerca volvulus provides first insights into the
      structure of the excretory system of this developmental stage of the parasite.
      The most anterior part of this system consists of a cell process of the syncytial
      excretory cells. At this height the excretory cells enclose the cuticle-lined
      excretory channel. The channel is in the process of elongation in the anterior
      posterior direction, indicated by cell division in this region. More posteriad an
      ampulla-like structure is forming in the cytoplasm of the excretory cells. The
      inner surface of this ampulla is lined with a small number of single microvilli.
      In this part of the system the cytoplasm of the excretory cells is rich in Golgi
      bodies and endocytic vesicles. The ampulla has direct access to the exterior by
      the excretory duct. The excretory duct is a cuticle-lined structure surrounded by
      supporting fibres of an additional cell. This duct cell connects the excretory
      duct to the body-wall cuticle at the excretory pore. Adjacent to the region of
      the excretory system a cell is found that resembles a gland cell. This cell is in
      close contact to the ventral nerve cord. The genital primordia of the third-stage
      juvenile consist of several dividing cells. The female genital primordium is seen
      at the junction of the muscular with the glandular oesophagus and the male
      primordium can be found at the junction of the glandular oesophagus with the gut.

PMID- 7501643
TI  - Occurrence of N-acetyl- and N-O-diacetyl-neuraminic acid derivatives in wild and
      mutant Crithidia fasciculata.
AB  - The cell-surface expression of sialic acids in wild-type Crithidia fasciculata
      and three drug-resistant mutants (FU(R)11, TR3, and TFRR1) was analyzed using
      fluorescein-labeled Limulus polyphemus agglutinin (LPA) binding, glycosidase of
      known sugar specificity, and thin-layer chromatography (TLC). Gas-liquid
      chromatography-mass spectrometry (GC-MS) analysis using both electron-impact (EI
      MS) and chemical ionization (CI-MS) by isobutane with selected ion monitoring
      (SIM) was also used. The surface location of sialic acid was inferred from LPA
      binding to whole cells abrogated by previous treatment with neuraminidase. An
      exception occurred with the TFRR1 strain, which after incubation with
      neuraminidase showed increased reactivity with the fluorescent lectin. Both N
      acetyl- and N-O-diacetyl-neuraminic acids were identified in the flagellates by
      TLC, with a clear predominance being noted for the former derivative. However,
      the content of N-O-diacetyl-neuraminic acid was preferentially found in the TFRR1
      strain. The GC-MS analysis of the acidic component of the TFRR1 mutant strain
      confirmed the occurrence of N-acetyl-neuraminic acid (Neu5Ac) by the presence of
      the diagnostic ions (m/z values: 684 and 594 for CI-MS and 478, 298, and 317 for
      EI-MS) and also by comparison with the standard Neu5Ac retention time. GC-MS
      analysis also showed fragments (m/z values: 654 and 564 for CI-MS and 594, 478,
      298, and 317 for EI-MS) expected for the 7-O- and 9-O-acetyl-N-acetyl-neuraminic
      acids (Neu5,7Ac2 and Neu 5,9Ac2, respectively).

PMID- 7501644
TI  - Serum levels of circulating anodic antigen and circulating cathodic antigen
      detected in mice infected with Schistosoma japonicum or S. mansoni.
AB  - Serum concentrations of circulating anodic antigen (CAA) and circulating cathodic
      antigen (CCA) were studied in mice infected with either Schistosoma japonicum or
      S. mansoni cercariae. Sera from uninfected mice were negative for both antigens.
      CAA was detectable in the S. japonicum-infected mice as early as at 2 weeks post
      infection (p.i.), and levels were higher in these animals than in the S. mansoni
      infected group during the full study period. At the moment of perfusion, 10 weeks
      p.i., a median of 9 and 29 worms, respectively, were recovered from the S.
      japonicum- and S. mansoni-infected mice, and the median CAA levels were 326 and
      27 ng/ml, respectively. In contrast, CCA levels were much lower in the S.
      japonicum-infected group (27 ng/ml) as compared with the S. mansoni-infected mice
      (282 ng/ml). These results suggest an important difference between S. japonicum
      and S. mansoni infections in CAA and CCA production and/or clearance and indicate
      a significant role for CAA in the diagnosis of human schistosomiasis japonicum.

PMID- 7501645
TI  - Anti-tubulin immunohistochemistry study of Echinococcus granulosus protoscolices
      incubated with albendazole and albendazole sulphoxide in vitro.
AB  - Tubulin content was immunohistochemically studied in Echinococcus granulosus
      protoscolices incubated with albendazole and albendazole sulphoxide alone or in
      combination. Tubulin immunoreactivity was very patent in the control
      protoscolices and was mainly located in the sucker region and the invagination
      channel of protoscolices. Treated protoscolices always showed less
      immunoreactivity than did control protoscolices. We concluded that albendazole
      and its metabolite albendazole sulphoxide produce tubulin alterations in E.
      granulosus protoscolices.

PMID- 7501646
TI  - Detection of an "epimastigote-like" intracellular stage of Trypanosoma cruzi.
AB  - Monoclonal antibody (mAb) DION 5.1b, derived from mice immunized with Trypanosoma
      dionisii, recognizes a 72/76-kD surface glycoprotein specific to the epimastigote
      stage of T. dionisii and T. cruzi. None of the three other stages of the T. cruzi
      life cycle expresses any DION 5.1b-specific epitope. However, mAb DION 5.1b
      labels an intracellular form with "epimastigote-like" morphology that appears to
      be late and transient in the intracellular cycle. This result suggests that the
      morphological similarity between the observed "epimastigote-like" intracellular
      form in mammals and the epimastigote form in insects may extent to the antigenic
      pattern.

PMID- 7501647
TI  - The SAG2 antigen of Toxoplasma gondii and the 31-kDa surface antigen of
      Sarcocystis muris share similar sequence features.
AB  - In the search for similar cysteine distribution patterns among surface antigens
      of members of the phylum of Apicomplexa, we found a resemblance between TgSAG2, a
      22-kDa surface antigen of Toxoplasma gondii, and the C-terminal half of a 31-kDa
      surface antigen of Sarcocystis muris, SmSAG1. The overall degree of similarity is
      low, corresponding to 28% of identity in the 146 amino acids aligned. However,
      the conservative spacing between the cysteine residues suggest that this
      similarity might have functional implications. The described amino acid
      similarity provides a new clue to the molecular relationship between two closely
      related coccidian parasites.

PMID- 7501648
TI  - Elucidation of the life cycle of the intestinal protozoan Blastocystis hominis.
AB  - This paper elucidates the status of the different morphological forms of
      Blastocystis and reports the existence of thin- and thick-walled cysts in B.
      hominis on the basis of current experimental evidence. It is suggested that the
      thin-walled cysts are autoinfectious, leading to multiplication of the organism
      in the intestinal tract. The thick-walled cysts are responsible for external
      transmission via the faecal-oral route. A life cycle for B. hominis is postulated
      on the basis of these findings.

PMID- 7501649
TI  - Role of 5-HT receptor subtypes in the modulation of dorsal periaqueductal gray
      generated aversion.
AB  - To explore the role of 5-HT receptor subtypes in controlling aversion, we
      measured the effect of 5-HT1A and 5-HT2A/2C receptor agonists microinjected into
      the dorsal periaqueductal gray (DPAG) of rats on aversive behavior induced by
      electrical stimulation of the same brain area. The 5-HT1A agonists 8-OH-DPAT (4
      16 nmol) and BAY-R-1531 (4-16 nmol) raised the threshold of aversive electrical
      stimulation in a dose-dependent way. Similarly, microinjection of the 5-HT2A/2C
      agonist DOI (4-16 nmol) increased the aversive mCPP (16 and 32 nmol) was
      ineffective. Previous intra-DPAG administration of the 5-HT1A receptor blocker
      NAN-190 (40 nmol) antagonized the antiaversive effect of 8-OH-DPAT (8 nmol),
      whereas pretreatment with the 5-HT2A receptor blocker spiperone (10 nmol)
      antagonized the effect of DOI (16 nmol). Spiperone also counteracted the effect
      of 8-OH-DPAT and NAN-190 counteracted the effect of DOI. These results indicate
      that activation of 5-HT1A and 5-HT2A receptors inhibits aversion in the DPAG and
      that both receptors have to be functional for the expression of each one's
      activation to occur.

PMID- 7501650
TI  - Meal pattern analysis in rats reveals partial agonist activity of the bombesin
      receptor antagonist BW2258U89.
AB  - The spontaneous feeding behavior of adult male rats was monitored during
      continuous infusion of the bombesin receptor antagonist BW2258U89 into the
      coeliac artery (100 micrograms kg-1 h-1) from an osmotic minipump. Nocturnal food
      intake was suppressed over 5 days of testing. Similar effects followed acute
      BW2258U89 treatment [100 micrograms kg-1, intraperitoneally (i.p.)]. Moreover,
      i.p. BW2258U89 mimicked the acute behavioral effects of 2 micrograms kg-1 i.p.
      bombesin by reducing meal size. Verifying that BW2258U89 can retain its potency
      throughout the entire period of chronic infusion, we demonstrated that the acute
      anorectic action of bombesin (4 micrograms kg-1, i.p.) was blocked by
      pretreatment with a BW2258U89 solution (100 micrograms ml-1 kg-1, i.p.) that was
      freshly prepared, or incubated for 1 or 6 days at body temperature. These data
      demonstrate that acute and chronic administration of BW2258U89, at a dose that
      abolishes the satiety effect of bombesin, significantly suppresses spontaneous
      feeding. Thus, BW2258U89 appears to attenuate food intake by acting as a partial
      agonist at peripheral receptors for bombesin-like peptides.

PMID- 7501651
TI  - Inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine apparently
      increases brain serotoninergic activity in the rat: no influence of previous
      chronic immobilization stress.
AB  - The functional relationship between brain catecholamines and serotoninergic
      function was studied in stress-naive and chronically immobilized rats after
      blockade of catecholamine synthesis with alpha-methyl-p-tyrosine (alpha MpT). The
      levels of noradrenaline (NA), serotonin, and 5-hydroxyindole acetic acid (5-HIAA)
      in pons plus medulla, brainstem, hypothalamus, hippocampus, and frontal cortex,
      and those of 3-methoxy, 4-hydroxyphenile-tileneglicol sulphate (MHPG-SO4) in the
      hypothalamus were measured by HPLC. Chronic immobilization (IMO) resulted in
      higher NA levels in pons plus medulla and hypothalamus, the latter area (the only
      one in which the NA metabolite was determined) also showing slightly elevated
      MHPG-SO4 levels as compared to stress-naive rats. Chronic IMO did not alter
      either serotonin or 5-HIAA levels, but acute stress consistently increased 5-HIAA
      levels in all areas, independently of previous chronic stress. Administration of
      alpha-MpT drastically reduced NA and increased 5-HIAA levels in all brain regions
      excepting the frontal cortex. The effect of the drug on serotoninergic function
      was not altered by previous chronic exposure to IMO. These data suggest that the
      noradrenergic system appears to exert a tonic inhibitory effect on serotoninergic
      activity in the brain, with the intensity of the effect depending on the brain
      area studied. In addition, chronic stress does not appear to alter the functional
      relationship between noradrenergic and serotoninergic activities, although
      interactions might exist in more restricted brain areas; this deserves further
      study.

PMID- 7501652
TI  - Contribution of "diazepam-insensitive" GABAA receptors to the alcohol antagonist
      properties of Ro 15-4513 and related imidazobenzodiazepines.
AB  - Both in vivo and in vitro studies have shown that Ro 15-4513 can antagonize many
      of the pharmacologic actions of ethanol. In contrast to many benzodiazepine
      receptor (BzR) ligands, Ro 15-4513 binds with high affinity to a novel GABAA
      receptor subtype, referred to as "diazepam-insensitive" (DI). This study examined
      the contribution of DI GABAA receptors to the modulation of ethanol-induced sleep
      time by Ro 15-4513 and related imidazobenzodiazepines [e.g., Ro 19-4603, Ro 16
      6028, and ZG-63 (t-butyl-8-chloro-5,6-dihydro-5-methyl-6-oxo-imidazo[1,5,a]
      [1,4]benzodiazepine-3-carboxylate)] that possess high affinities for this GABAA
      receptor subtype. Ro 15-4513 (0.6-5 mg/kg) significantly reduced ethanol (3.5
      g/kg, i.p.) sleep time in mice (p < 0.001, analysis of variance). This effect was
      not blocked by BzR antagonists ZK 93426 (5 mg/kg) and Ro 14-7437 (5 mg/kg), which
      possess low affinities for DI but bind with high affinities to other "diazepam
      sensitive" (DS) GABAA receptor isoforms. Although Ro 19-4603 (2.5 mg/kg) also
      reduced ethanol sleep time (p < 0.01), this effect was attenuated by
      coadministration of ZK 93426 (2.5 mg/kg). Ro 16-6028 (2.5 mg/kg) prolonged (p <
      0.01) ethanol sleep time. However, in the presence of either Ro 19-7437 (5 mg/kg)
      or ZK 93426 (2.5 mg/kg) ethanol-induced sleep time was reduced to values
      approaching those obtained with ethanol in the presence of Ro 15-4513. A low dose
      (2.5 mg/kg) of ZG-63 did not significantly affect alcohol sleep time. However, in
      the presence of ZK 93426, ZG-63 increased sleep time (p < 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7501653
TI  - Chronic phenytoin induced impairment of learning and memory with associated
      changes in brain acetylcholine esterase activity and monoamine levels.
AB  - Groups of adult, male, Wistar rats were administered phenytoin (DPH) at 5, 12.5,
      25, 50, or 75 mg/kg i.p. for 21 days. The learning and memory of these rats were
      assessed using the T-maze and passive avoidance tests. The plasma DPH levels,
      acetylcholine esterase (AChE) activity in different brain regions, and the levels
      of monoamines in the hippocampus were measured. The results indicate that DPH
      below the therapeutic plasma level did not significantly impair learning and
      memory. Correspondingly, no changes were noted in the brain 5-HT or AChE
      activity. However, DPH, at therapeutic plasma concentrations (i.e., 10.5
      micrograms/ml in the dosage range of 50 and 75 mg/kg, respectively),
      significantly impaired learning and memory in rats. The impaired learning and
      memory functions were associated with increased 5-HT levels and decreased AChE
      activity in the hippocampus. With a dose of 75 mg/kg DPH, there was a reduction
      in the AChE activity in the striatum, in addition to hippocampus. It is
      conjectured that the neurochemical changes brought about by DPH at therapeutic
      plasma levels may account for the impairment of learning, memory, and cognitive
      functions in epilepsy.

PMID- 7501654
TI  - The effects of nicotine and nicotine withdrawal on taste reactivity.
AB  - The effect of nicotine pretreatment on the palatability of flavored solutions was
      assessed using the taste reactivity test. In Experiment 1, low doses of nicotine
      [0.2-0.4 mg/kg, subcutaneously (s.c.)] suppressed the aversive taste properties
      of quinine and quinine-sucrose mixture and enhanced the hedonic taste properties
      of sucrose (0.4 mg/kg, s.c.) in rats that were nicotine naive. In Experiment 2,
      rats were chronically preexposed to nicotine or saline over a period of 21
      pretreatment days. Tolerance developed to the ability of nicotine to enhance the
      palatability of sucrose. Furthermore, rats that were chronically preexposed to
      nicotine displayed enhanced hedonic evaluation of sucrose 24 h after nicotine was
      withdrawn. These results confirm human self-reports that withdrawal from nicotine
      dependency enhances the palatability of sweet-tasting foods.

PMID- 7501655
TI  - The D1 agonist SKF 38393 attenuates amphetamine-produced enhancement of
      responding for conditioned reward in rats.
AB  - The present study investigated the hypothesis that the D1 subtype of DA receptors
      is critically involved in reward-related learning. The effects of SKF 38393, a D1
      specific agonist, on amphetamine-produced enhancement of responding for
      conditioned reward were tested. We exposed 69 male Wistar rats to an experimental
      design consisting of three phases. The preexposure phase consisted of five
      sessions during which the rats were exposed to an operant chamber containing two
      levers. One lever produced a lights-off stimulus (3 s) and the other a tone
      stimulus (3 s). This was followed by four conditioning sessions during which the
      levers were removed and the rats were exposed to pairings of the lights-off
      stimulus with food. This phase was followed by two test sessions during which the
      levers were present and the number of responses made on each lever was calculated
      as a ratio of the number of responses made during the preexposure phase. A group
      receiving saline during the test sessions showed a higher ratio of responding for
      the lights off stimulus than the tone stimulus, demonstrating that the lights-off
      stimulus had become a conditioned reward. Amphetamine [2.0 mg/kg,
      intraperitoneally (i.p.), 5 min before the test] enhanced responding specifically
      on the lever producing the conditioned reward. Groups receiving SKF 38393 (5.0,
      10.0, and 20.0 mg/kg, i.p., 5 min before the test) failed to show significantly
      greater responding for the lights-off stimulus than the tone, indicating a
      reduction or elimination of the conditioned reward effect. Moreover, SKF 38393
      dose dependently reduced the amphetamine-produced enhancement of responding for
      conditioned reward.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501656
TI  - Dose-dependent surmountability of locomotor activity in caffeine tolerance.
AB  - For two chronic intraperitoneal caffeine dose regimens (10 and 80 mg/kg per day),
      tolerance developed rapidly (2-3 days) to the stimulatory effects of caffeine on
      locomotor activity. However, surmountability of the tolerant activity rate levels
      by caffeine administration was dose dependent: Activity rate was restored fully
      by acute caffeine administration for the 10 mg/kg per day series, but not for the
      80 mg/kg per day series. The extent of tolerance was also dose-dependent:
      Tolerance was incomplete for the low-dose daily caffeine series but complete for
      the high-dose series. Upon discontinuation of daily caffeine dosing, activity
      rate decreased to the original baseline levels for both chronic series. Caffeine
      tolerance and the quantification of its surmountability may be explained by the
      pharmacokinetics of caffeine and the upregulation of adenosine receptors.

PMID- 7501657
TI  - Implication of endogenous opioid system in the learned helplessness model of
      depression.
AB  - The involvement of opioid system on the learned helplessness model of depression
      was investigated. Animals preexposed to inescapable shocks were treated with
      either Met-enkephalin, Leu-enkephalin, morphine, imipramine, naloxone, RB 38A (a
      mixed inhibitor of enkephalin degrading enzymes), or RB 38B (a selective
      inhibitor of neutral endopeptidase EC 3.4.24.11). Stimulation of opioid system by
      either opioid agonists or enkephalin catabolism inhibitors reversed the escape
      deficit induced by shock pretreatment. In contrast, administration of naloxone
      potentiated the effect of inescapable shocks. Imipramine reduced the number of
      escape failures in this test, and this effect was antagonized by naloxone. These
      results point to the involvement of the endogenous opioid system in this model of
      depression.

PMID- 7501658
TI  - The delta 2-opioid receptor antagonist naltriben selectively attenuates alcohol
      intake in rats bred for alcohol preference.
AB  - The relative importance of different opioid receptor types in mediating alcohol
      drinking behavior compared with the intake of other ingesta can be determined by
      characterizing the effects of selective opioid antagonists on the intake of
      various ingesta. Nonselective opioid receptor antagonists suppress the intake of
      many ingesta including alcohol, food, water, and sweets. Two distinct subtypes of
      delta-opioid receptors, delta 1 and delta 2, have recently been identified in
      rodent brain. We have previously reported that naltrindole (NTI), which blocks
      both delta 1 and delta 2 receptors, suppresses both alcohol and saccharin intake
      in rats selectively bred for high alcohol preference (P line). We now report that
      naltriben (NTB), an opioid antagonist that is selective for delta 2-opioid
      receptors, suppresses alcohol intake in rats of the P line and the effect appears
      to be both specific for alcohol and independent of alcohol palatability. NTB may
      reduce alcohol intake by attenuating the reinforcing pharmacological properties
      of alcohol.

PMID- 7501659
TI  - CRF administered to pregnant rats alters offspring behavior and morphology.
AB  - Pregnant rats injected with 20 micrograms of corticotropin-releasing factor (CRF)
      from day 14 through 21 gained less weight during gestation than did saline
      injected controls. The offspring of CRF-injected females differed from the
      offspring of control females in several ways: males and females weighed less
      during the first 2 weeks of life, males had shorter anogenital distances at
      birth, and males and females emitted more ultrasonic vocalizations during
      isolation in tests at 6 and 14 days of age. These effects are similar to those
      that have been observed following exposure of pregnant females to stressors, and
      provide support for the notion that CRF and/or CRF activation of the hypothalamic
      pituitary-adrenal axis mediate effects of gestational stress.

PMID- 7501660
TI  - Diurnal rhythms of paraventricular hypothalamic norepinephrine and food intake in
      rats.
AB  - Extracellular levels of endogenous norepinephrine (NE) within rat paraventricular
      hypothalamus (PVN) vary across the diurnal cycle, with a peak in NE level noted
      at the onset of the dark cycle, at which time feeding occurs in a burst. The
      present experiment further examined the relationship between food intake and
      extracellular levels of NE within the PVN and within sites located outside of the
      hypothalamus. Adult male rats were implanted with concentric microdialysis probes
      aimed at either the PVN or brain sites outside the PVN. Measures of food intake
      and of extracellular NE were collected every hour over a 24-h period. Rats with
      PVN probes exhibited two peaks in extracellular NE. The first peak in PVN NE
      occurred within 1 h before the onset of the dark phase (ZT11) and was
      significantly correlated (p < 0.02) with a marked burst of feeding during the
      first hour of the dark phase. In addition, a second NE peak occurred 8 h into the
      dark phase (ZT19) but was not accompanied by feeding. Rats bearing non-PVN probes
      did not exhibit alterations in extracellular NE yet did show a pattern of feeding
      similar to that noted in the PVN rats. These data support the hypothesis that the
      burst of feeding evident at the onset of dark is related, in part, to an increase
      in PVN extracellular NE.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501661
TI  - Autosomal and Y chromosomal effects on the stereotyped response to apomorphine in
      wild house mice.
AB  - The behavioral response to apomorphine, a dopamine agonist, was shown to be
      different between a selection line characterized by Short Attack Latencies (SAL)
      and a selection line having Long Attack Latencies (LAL) (4). Aggressive SAL mice
      were more sensitive to apomorphine than nonaggressive LAL males. The aim of this
      research was to determine whether the stereotyped response to apomorphine is
      affected by the Y chromosome in the same way as it influences attack latency. For
      this purpose, F1 reciprocal hybrids as well as congenic lines (SAL.LY and LAL.SY)
      were used. The major difference between the congenic and parental lines is the
      nonpairing part of the Y chromosome (non-PAR). Apomorphine was injected
      subcutaneously at a preselected dose level of 5.0 mg/kg to induce stereotyped
      behavior manifested in compulsive sniffing, gnawing, and licking. Both the
      autosomes and the non-PAR Y chromosome affected the response to apomorphine. The
      effect of the autosomes was in accordance with the aggression data, whereas the
      effect of the non-PAR Y chromosome was different, and suggests a specific
      relation between dopamine systems and the non-PAR Y chromosome.

PMID- 7501662
TI  - 1,3-Di-o-tolylguanidine (DTG) differentially affects acute and tonic formalin
      pain: antagonism by rimcazole.
AB  - The role of the sigma receptor in prolonged pain was examined by assessing the
      effects of 1,3,di-o-tolylguanidine (DTG), a selective sigma receptor ligand, on
      the formalin test in mice. Formalin injected subcutaneously into the hindpaw
      produces a biphasic pain response: an acute phase of short duration followed by a
      longer-lasting tonic phase. DTG (10 mg/kg, i.p.) potently reduced pain behavior
      in the acute phase but increased pain behavior in the tonic phase. Rimcazole (5
      and 10 mg/kg, i.p.), a selective sigma receptor antagonist, blocked both the DTG
      induced decrease and increase in pain behavior observed in the acute and tonic
      phases, respectively. These data support previous findings indicating a
      modulatory role for the sigma receptor in nociceptive processes, and suggest that
      this receptor differentially modulates acute vs. tonic pain.

PMID- 7501663
TI  - Rats self-inject a dopamine antagonist in the lateral hypothalamus where it acts
      to increase extracellular dopamine in the nucleus accumbens.
AB  - Local injection of sulpiride to block dopamine (primarily D2-type) receptors in
      the perifornical lateral hypothalamus (pf-LH) can induce locomotion, feeding, and
      drinking, and in the present study, local sulpiride induced reward and dopamine
      (DA) release in the nucleus accumbens. Sulpiride injected bilaterally (4, 8, and
      16 micrograms/0.3 microliters), ipsilaterally, or contralaterally (8 micrograms)
      in the pf-LH increased extracellular levels of DA and its metabolites in the
      accumbens. Bilateral sulpiride injected posterior and medial to the pf-LH
      controlled for diffusion to the ventricle or ventral midbrain. Rats self-injected
      sulpiride (210 ng/21 nl/2 s) in the pf-LH (111 resp/2 h on drug lever vs. 20 resp
      on a blank lever). Thus, cells in the pf-LH establish connections with mesolimbic
      DA neurons involved in the behavior reinforcement process. Evidently hypothalamic
      cells with DA receptors normally inhibit aspects of behavior reinforcement.
      Disinhibition with hypothalamic sulpiride is reward for self-injection and cause
      of overeating that can lead to obesity.

PMID- 7501664
TI  - Environmental pollutants alter taste responses in the gerbil.
AB  - Taste and smell are chemical senses that play a crucial role in food selection.
      Damage to taste and smell receptors can impair food intake, nutritional status,
      and survival. The purpose of this study was to determine the effects of 11
      environmental pollutants (nine insecticides and two herbicides) on
      electrophysiological taste responses in the gerbil. Integrated chorda tympani
      (CT) recordings were obtained from gerbils to a range of tastants before and
      after a 4-min application of 1 of 11 environmental pollutants. The taste stimuli
      were: sodium chloride (100 mM), calcium chloride (300 mM), magnesium chloride
      (100 mM), HCl (10 mM), potassium chloride (500 mM), monosodium glutamate (MSG)
      (50 mM), sucrose (100 mM), fructose (300 mM), sodium saccharin (10 mM), quinine
      HCl (30 mM), and urea (2 M). The nine insecticides included organophosphorous,
      carbamate, and pyrethroid insecticides. The seven organophosphorous insecticides
      tested were: acephate, carbofuran, chlorpyrifos, chlorpyrifos oxon, demeton,
      malathion, and methamidophos. The carbamate insecticide carbaryl and the
      pyrethroid insecticide fenvalerate were also tested. Two herbicides, paraquat and
      glyphosate, were tested, and dose-response curves for each of these two
      herbicides were also determined. All of the 11 insecticides and herbicides had an
      effect on some of the taste stimuli tested. Application of 10 mM methamidophos
      exhibited the greatest amount of suppression on the 11 taste solutions. Each
      taste stimulus was significantly suppressed with the exception of 2 M urea.
      Herbicides paraquat and glyphosate also reduced responses to several tastants.
      These data indicate that environmental pollutants can modify taste responses in
      the gerbil.

PMID- 7501665
TI  - Smokers' behaviour and exposure according to cigarette yield and smoking
      experience.
AB  - The influence of cigarette yield and length of smoking experience on smoking
      behaviour and biomarker levels was sought in 108 smokers who have never changed
      cigarette class. Smoking parameters carboxyhaemoglobin percentage (COHb), urinary
      nicotine, and its metabolites, mutagens, and thioethers were measured. Cigarette
      yield does not affect daily consumption or smoke volume puffed per cigarette. But
      the inhalation depth increases with decreasing cigarette yield and with length of
      smoking habit. The COHb level after the first cigarette in the morning increases
      significantly with CO cigarette yield and length of smoking experience. In the
      evening, only the cigarette yield has an effect on COHb level. Biomarker levels
      excreted in urine are generally lower for females than for males. They tend to
      increase with smoking history. Only COHb level and total urinary nicotine
      metabolites (Barlow index) are weakly correlated with cigarette yield. The
      absence of significant differences due to cigarette class in urinary biomarkers
      can be explained by changes in inhalation depth, individual differences of
      metabolism, and limited specificity of some markers (mutagens, thioethers).

PMID- 7501666
TI  - Linopirdine does not improve matching performance in the titrating matching-to
      sample paradigm.
AB  - Linopirdine (DUP 996), a proposed cognitive enhancing agent, was studied in four
      squirrel monkeys (Saimiri sciureus) and six White Carneau pigeons responding
      under a titrating matching-to-sample paradigm (TMTS). Briefly, under this
      titration schedule, each trial began with the presentation of a sample stimulus
      on the center key of a three-key pigeon or squirrel monkey chamber. Completion of
      a fixed-ratio on the center key resulted in the termination of the stimulus
      presentation and the initiation of a delay period. The length of the delay
      changed as a function of the subject's performance. During the first five trials
      of each session, the delay was fixed at 3 s in length. On the sixth and all
      subsequent trials, the length of the delay increased, did not change, or
      decreased such that accuracy was maintained at approximately 80%. Following the
      delay, two of the three response keys were transilluminated with different
      colored lights. A single response on the key transilluminated with the same
      stimulus as the sample stimulus resulted in the presentation of food. A response
      on the key transilluminated with the stimulus that did not match the sample
      stimulus resulted in a timeout. Linopridine was administered in the pigeon (0.001
      5.6 mg/kg) and squirrel monkey (0.01-1.0 mg/kg) 15 min before testing. Matching
      performance was not affected as measured by changes in mean delay values or
      percent accuracy even at doses that decreased rate of responding. These results
      suggest that the enhancement in cognitive function previously reported after
      administration of linopiridine may be limited to specific situations.

PMID- 7501667
TI  - Effect of cocaine on sexual behaviour in male stumptail macaques (Macaca
      arctoides).
AB  - The effect of cocaine (0.01-1.0 mg/kg) on sexual behaviour was studied in four
      male stumptail macaques (Macaca arctoides). Following drug-saline control
      administration, the behaviour of the male monkey with a female was observed for
      30 min in two different behavioural conditions; in one of the conditions the
      baseline sexual activity was low, and in the other it was high (partial or
      complete separation of the male and the female between the sessions,
      respectively). The reversal of the cocaine-induced effects was attempted by
      haloperidol (0.003-0.01 mg/kg), a dopamine-2-receptor antagonist. Cocaine (0.1
      1.0 mg/kg) produced a highly significant dose-dependent suppression in the number
      of ejaculations. The cocaine-induced suppression of ejaculatory behaviour was
      completely reversed by haloperidol. Haloperidol at the dose range used did not in
      itself influence ejaculatory behaviour. The effect of cocaine on grooming,
      nonejaculatory mounting, aggression, or perineal investigations did not reach
      statistical significance. The possibility that cocaine at very low doses (0.01
      0.1 mg/kg) might increase sexual activity was excluded in the behavioural
      condition with a low basal sexual activity. The results indicate that cocaine
      dose-dependently suppresses ejaculatory behaviour as a result of dopamine-2
      receptor-mediated mechanisms. The cocaine-induced suppression of ejaculatory
      behaviour might be explained by the strong rewarding effect of cocaine alone.

PMID- 7501669
TI  - Striatal dopamine-mediated motor behavior is altered following occlusion of the
      middle cerebral artery.
AB  - Cerebral infarct (stroke) causes striatal damage with subsequent deterioration of
      sensorimotor and cognitive functions that may be mediated by the dopamine
      receptor system. In the present study, transient, focal ischemia was induced in
      Sprague-Dawley rats by middle cerebral artery occlusion. Ischemic animals
      exhibited significantly less dopamine antagonist (haloperidol)-induced catalepsy
      and more dopamine agonist (amphetamine)-induced hyperactivity than sham-operated
      animals. Younger ischemic animals showed more profound behavioral alteration but
      also displayed greater recovery over time than older ischemic animals. Histologic
      data revealed a lateral striatal lesion in all ischemic animals. These results
      place the striatal dopaminergic system as a possible strategic venue for the
      treatment of cerebral ischemia. In addition, aging is found to be a risk factor
      for stroke as noted in humans.

PMID- 7501668
TI  - Antagonism by intracerebellar Ro15-4513 of acute ethanol-induced motor
      incoordination in mice.
AB  - The possible antiethanol effect of intracerebellarly microinjected Ro15-4513 was
      investigated using motor incoordination as the test response. The results of this
      study further confirmed reports from this and other laboratories that this
      partially negative ligand of benzodiazepine selectively attenuated and nearly
      reversed the motor impairment of acute ethanol. The attenuation observed after
      microinjections of doses of 0.05, 0.1, and 0.5 ng was significant and dose
      related. There was no effect on normal coordination when the highest dose, 0.5
      ng, was administered followed by saline instead of a test dose of ethanol. When
      0.5 ng of Ro15-4513 alone was microinjected into the cerebellum, no significant
      change in the locomotor activity was observed. Even a 10-fold higher
      intracerebellar dose (5 ng) of Ro15-4513 administered alone produced no
      significant changes in locomotor activity. This suggests that attenuation of
      ethanol-induced motor incoordination was most likely due to the selective
      antiethanol effect of Ro15-4513 at the dose range used in the present
      investigation. The antiethanol effect of intracerebellar Ro15-4513 also
      reaffirmed the well-known belief that the cerebellum is an important brain region
      for ethanol's motor-impairing effect. The results also indirectly suggest the
      inhibition of GABAA-gated chloride ion channel activity as the most likely basis
      of Ro15-4513's antiethanol effect.

PMID- 7501670
TI  - Influences of housing conditions and ethanol intake on binding characteristics of
      D2, 5-HT1A, and benzodiazepine receptors of rats.
AB  - The effects of different housing conditions and ethanol treatment (6 vol % in the
      drinking water) on the in vitro binding characteristics of striatal dopaminergic
      D2 ([3H]spiperone), hippocampal serotonergic 5-HT1A ([3H]8-OH-DPAT), and cortical
      benzodiazepine ([3H]flunitrazepam) receptors have been examined. Social
      deprivation due to contact caging, short- (1 day) and long-term isolation (5
      weeks) yielded a significant decrease of striatal D2 receptor density with the
      greatest decrease after long-term isolation (-21% Bmax) without changes of Kd in
      comparison to group animals. The effect of ethanol on striatal D2 receptor
      density depended on the housing conditions. Whereas ethanol treatment reduced
      receptor density of group animals (down to 88%), chronic exposure to ethanol
      under long-term isolation elicited no significant alteration of D2 receptor
      density compared with group animals. Different housing and ethanol treatment had
      no effect on 5-HT1A receptor affinity and density. Alterations of benzodiazepine
      receptor density were not found, but social deprivation as well as ethanol
      treatment of group animals caused an increased affinity of [3H]flunitrazepam
      (reduced Kd value). These results indicate that different housing conditions of
      adult rats evoked significant alterations in D2 and benzodiazepine receptor
      binding assays, which were modified by ethanol treatment in the case of striatal
      D2 receptor density.

PMID- 7501671
TI  - The effects of different doses of caffeine on habituation of the human acoustic
      startle reflex.
AB  - Research in this laboratory showed that caffeine (4 mg/kg) delays habituation of
      the acoustic startle reflex in humans. The present study examined the effects of
      2- and 6-mg/kg doses of caffeine on acoustic startle habituation in moderate-high
      and low caffeine users. Eyeblink responses to 30 trials of 85-dB noise stimuli
      were measured beginning 30 min after oral ingestion of either placebo or 2 or 6
      mg/kg of caffeine. The 2-mg/kg dose of caffeine delayed startle habituation in
      both moderate-high and low caffeine users. The 6-mg/kg dose produced no
      differential effects on startle responding from placebo. In moderate-high users,
      following habituation, startle responding was smaller in the placebo condition
      compared to both caffeine conditions. In low users there were no differences in
      posthabituation responding between doses, suggesting that this dose effect is
      dependent on a history of chronic caffeine usage.

PMID- 7501672
TI  - Complementary memory storage sites in mice: their development as affected by the
      competitive NMDA receptor antagonist, CPP.
AB  - Bitemporal injections of puromycin consistently induce amnesia of aversive maze
      learning in mice when administered within 3 days of training. These bitemporal
      puromycin injections lose their amnestic effectiveness if the latency between
      training and injection is extended beyond 6 days. Consistent with other evidence,
      we conclude that in our experimental paradigm, complementary memory storage sites
      normally develop in additional cerebral areas within 6 days following training.
      Previous experiments have indicated that the central adrenergic and cholinergic
      systems are critically involved in this process. We now present evidence that
      administration of the NMDA receptor antagonist, CPP, blocks the development of
      these complementary memory storage sites. As suggested by studies of long-term
      potentiation, NMDA receptor-dependent postsynaptic calcium appears to be
      essential for the development of these storage sites and indeed to trigger their
      development.

PMID- 7501673
TI  - Evidence for an action of araboascorbic acid on dopaminergic pathways of the
      corpus striatum.
AB  - The relative decrease in the 2 h accumulation of administered [3H]-spiperone
      (SPI)-2 muCi/kg, 0.0004 mg/kg, s.c. - in mouse corpus striatum, a brain area with
      a high dopaminergic input (specific plus nonspecific dopamine receptor ligand
      binding) and the cerebellum, a brain area with little, if any, dopaminergic input
      (an index of nonspecific dopamine receptor ligand binding) were used to compare
      the influence of araboascorbic acid (AraA) with ascorbic acid (AsA) on the
      dopamine receptor. The abilities of these compounds to potentiate haloperidol
      induced catalepsy were also investigated. Pretreatment for 30 min with AraA (1000
      or 2000 mg/kg, i.p.) produced the same dose-dependent decrease in SPI
      accumulation in corpus striatum as observed with AsA. Accumulation in cerebellum
      was unaffected by either agent. Furthermore, as previously shown for AsA in rats
      and monkeys, AsA (1000 mg/kg) potentiated the cataleptogenic effect of
      haloperidol (0.2 mg/kg, s.c.). AraA was at least as effective as AsA in
      potentiating catalepsy produced by the neuroleptic. Thus, it would appear that
      AraA influenced the dopamine receptor in a manner not unlike that already shown
      for AsA. Because both agents have almost identical redox potentials but divergent
      antiscorbutic activities, their reductive properties might be more pertinent to
      the observed effects than their antiscorbutic properties.

PMID- 7501674
TI  - The lethal effects of ethanol and cocaine and their combination in mice:
      implications for cocaethylene formation.
AB  - The HS line of mice was used to determine the LD50 values for cocaine and
      ethanol, as well as for cocaethylene, the enzymatic product of their
      coadministration. The LD50 of cocaethylene was found to be significantly lower
      than that of cocaine, and both were more potent in their lethality than ethanol.
      When a low-lethality dose of cocaine was administered with a nonlethal dose of
      ethanol, the result was a significant increase in the prevalence of lethality.
      Thus, the lethal effects of the dose of cocaine used were increased by the dose
      of ethanol administered such that the two drugs in combination were equipotent to
      cocaethylene. The results are discussed in light of the ability of the liver, via
      transestification, to rapidly form cocaethylene from cocaine in addition to
      ethanol's ability to decrease the catabolism of cocaine. Thus, the possibility
      exists that the increased lethality observed is produced by both the production
      of the more lethal cocaethylene and sustained levels of cocaine.

PMID- 7501675
TI  - Effect of ethanol on extracellular dopamine in the nucleus accumbens of alcohol
      preferring AA and alcohol-avoiding ANA rats.
AB  - The role of central monoamines in the genetically determined influences on
      voluntary ethanol consumption were examined by studying the extracellular levels
      of monoamines in the nucleus accumbens of the alcohol-preferring AA (Alko
      Alcohol) and alcohol-avoiding ANA (Alko Nonalcohol) rats with in vivo
      microdialysis. Dialysate samples for the assay of monoamines with small bore HPLC
      were collected from freely moving animals at 15 min intervals after
      administration of ethanol (0.5, 1, or 2 g/kg, i.p.). Ethanol significantly
      increased the extracellular levels of dopamine, DOPAC, and HVA, suggesting
      stimulation of dopamine release by ethanol, while the effect on 5-HIAA did not
      reach significance. No difference in the extent or time course of stimulation of
      dopamine release between the AA and ANA rats was found. The results could so far
      give no indication that the differential ethanol consumption by AA and ANA rats
      could be explained in terms of differences in ethanol-induced stimulation of
      dopamine release in the nucleus accumbens.

PMID- 7501676
TI  - Assessment of motivational aspects involved in initiation of cocaine and heroin
      self-administration in rats.
AB  - A behavioral paradigm was explored to assess the motivational aspects involved in
      drug-taking behavior during initiation of drug self-administration. In separate
      saline-controlled experiments, naive animals were allowed to self-administer
      either cocaine or heroin (0.16 and 0.32 mg/kg per infusion) during five
      consecutive daily 3-h sessions by pressing one of two levers present in the test
      cage. During 15 min preceding the last four self-administration sessions, the
      animals had access to the levers but pressing the reinforcement lever did not
      result in a drug infusion. The animals properly self-administered both doses of
      cocaine and heroin, because the amount of self-infusions was higher than their
      saline control groups. Animals self-administering the high dose of cocaine and
      either dose of heroin performed lever-press behavior during the preceding period
      in a similar fashion as during the self-administration sessions, suggesting that
      this behavior during the preceding period was performed in the absence of the
      primary reinforcer, this behavior likely reflects the motivational state of
      animals to obtain the drug reinforcer, and thus may serve as a measure of the
      motivational aspects involved in the initiation of drug self-administration.

PMID- 7501677
TI  - REM sleep deprivation alters dopamine D2 receptor binding in the rat frontal
      cortex.
AB  - REM sleep deprivation (RSD) of rats results in facilitation of dopaminergic
      behavior and an increase in striatal D2 receptor density. To determine whether
      RSD results in changes in D2 receptor in other brain regions, receptor affinity
      (Kd) and density (Bmax) were measured in the anteromediofrontal (AM), cingulate
      (CN), and sulcal cortex (SL) in four groups of rats: 1), RSD96 group (RSD for 96
      h; small pedestal/water tank method), 2) RSD24 group (large pedestals for 72 h
      then small pedestals for 24 h), 3) tank control group (TC; large pedestals for 96
      h), and 4) cage control group. In separate groups, ambulation was recorded for 30
      min following treatments. Group RSD96 showed an increase in activity compared to
      TC, and TC was increased compared to CC (p < 0.05 for all). In group RSD24, the
      AM showed an increase in Bmax and Kd (p < 0.05), but there were no effects by
      RSD96. In the CN, Bmax and Kd were decreased by RSD96 (p < 0.05) but not RSD24.
      In the SL, Bmax was increased by RSD96, but not RSD24, whereas Kd was increased
      in both RSD groups (p < 0.05).

PMID- 7501678
TI  - Effect of lipid-derived second messengers on electrophysiological taste responses
      in the gerbil.
AB  - Integrated chorda tympani (CT) recordings were made to salty, sour, sweet,
      bitter, and glutamate tastants before and after a 4-min application of modulators
      of lipid-derived second messenger systems. The modulators included two membrane
      permeable analogues of DAG, 1-oleoyl-2-acetyl glycerol (OAG) and dioctanoyl
      glycerol (DiC8); thapsigargin, which releases Ca++ from intracellular stores;
      ionomycin, a calcium ionophore; lanthanum chloride, an inorganic calcium channel
      blocker; nifedipine, a dihydropyridine calcium channel blocker; quinacrine diHCl,
      a phospholipase A2 antagonist; melittin, a phospholipase A2 agonist; and
      indomethacin, which decreases the release of prostaglandins by inhibiting the
      enzyme cyclo-oxygenase. The main findings were: OAG (125 microM) and DiC8 (100
      microM) blocked the responses of several bitter compounds while enhancing the
      taste response to several sweeteners. Lanthanum chloride blocked all responses,
      which may be due to the fact that it blocks tight junctions. Quinacrine (1 mM)
      suppressed several bitter responses while enhancing the response to several
      sweeteners. The enhancement of sweet taste responses by DAG analogues suggests
      that there is cross-talk between the adenylate cyclase system and one (or more)
      pathways involving lipid-derived second messengers in taste cells.

PMID- 7501679
TI  - Suppression of ethanol intake in alcohol-preferring rats by prior voluntary
      saccharin consumption.
AB  - In a situation offering a free choice between 0.1% saccharin solution and tap
      water, Fawn Hooded (FH) rats consumed 363.0 +/- 33.5 ml/kg/day of saccharin
      solution. Subsequently those animals drank 3.0 +/- 0.4 g/kg of ethanol in a free
      choice between water and 10% ethanol solution. Control FH rats that did not have
      access to saccharin consumed 5.0 +/- 0.5 between groups was significant: p =
      0.006). When control rats were exposed to the choice between 10% ethanol solution
      and 0.1% saccharin solution for 4 days they consumed 383.7 +/- 27.5 ml/kg/day of
      saccharin solution and their ethanol intake dropped to 1.2 +/- 0.3 g/kg/day. When
      these rats were returned back to alcohol/water choice and exposure to saccharin
      was discontinued, their alcohol intake was still reduced (3.7 +/- 0.3 g/kg/day
      for at least 10 consecutive days). Exposure of alcohol-experienced alcohol
      preferring P rats with high (6.8 +/- 0.5 g/kg/day) and stable alcohol intake to
      saccharin/water choice for 4 days also resulted in a significant attenuation of
      their ethanol intake for at least 6 days following saccharin cessation. Thus,
      voluntary consumption of saccharin can suppress subsequent alcohol intake in both
      alcohol-naive and alcohol-experienced rats.

PMID- 7501680
TI  - Median raphe injections of 8-OH-DPAT lower frequency thresholds for lateral
      hypothalamic self-stimulation.
AB  - The selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)
      reduces the activity of brain 5-HT neurons via somatodendritic autoreceptors
      located in the midbrain raphe nuclei. This action of 8-OH-DPAT results in reduced
      5-HT synthesis and release of 5-HT in terminal regions. Previous studies have
      shown that injecting 8-OH-DPAT into the raphe nuclei stimulates feeding, sexual
      behaviour, and locomotor activity, and serves as an unconditioned stimulus for
      inducing a conditioned place preference. This behavioural profile suggests that
      raphe injections of 8-OH-DPAT facilitate reward-related behaviour. The present
      study tested this hypothesis by investigating the effects of median raphe
      injections of 8-OH-DPAT on sensitivity to lateral hypothalamic (LH) self
      stimulation. Frequencies required to sustain half-maximal rates of responding
      were determined following injection of saline or various doses of 8-OH-DPAT (0.2
      5 micrograms) into the median raphe. In four rats with accurate injection sites 8
      OH-DPAT dose-dependently lowered frequency thresholds by up to 40%. In the
      remaining rats injection sites were located outside the median raphe, and 8-OH
      DPAT either slightly raised or failed to lower frequency thresholds. These
      results show that 8-OH-DPAT injected into the median raphe facilitates brain
      stimulation reward, and suggest that acute reductions in 5-HT neurotransmission
      may enhance sensitivity to rewarding stimuli. The possible interactions between 5
      HT neurons and efferent systems utilizing dopamine and acetylcholine as
      neurotransmitters in mediating this effect are discussed.

PMID- 7501681
TI  - Differential effects of CGS 12066B and CP-94,253 on murine social and agonistic
      behaviour.
AB  - Although it has been previously proposed that 5-HT1B agonism specifically
      attenuates rodent agonistic behaviour, more recent investigations have indicated
      that such influences may be ancillary to an anxiogenic effect. The present study
      examined the influences of two 5-HT1B agonists, CGS 12066B and CP-94,253, on
      murine agonistic behaviour. In a resident-intruder paradigm, CGS 12066B (0.5-5.0
      mg/kg) decreased resident offensive aggression, social interest, and exploration
      while dose-dependently enhancing defensive behaviours across the dose range
      tested. CP-94,253 (2.5-10.0 mg/kg) also reduced elements of resident offensive
      behaviour whereas defensive behaviours were largely unchanged. Some elements of
      resident nonsocial and social behaviour were enhanced at 2.5 and 5.0 mg/kg but
      decreased at 10.0 mg/kg. The behavioural profile of CP-94,253, but not CGS
      12066B, supports the proposal that 5-HT1B receptors inhibit agonistic behaviour
      without concomitant sedative or anxiogenic effects. Findings are discussed in
      relation to 5-HT1A/1B/2C receptors involved in agonistic behaviour and anxiety.

PMID- 7501682
TI  - Higher environmental temperature-induced increase of body temperature:
      involvement of central opioidergic-GABAergic interaction.
AB  - Exposure (2 h) of male albino rats to higher environmental temperature (HET, 40
      degrees C) significantly increased the body temperature (BT). Administration of
      bicuculline (1 mg/kg, i.p.), physostigmine (0.2 mg/kg, i.p.), or their
      combination significantly raised the BT of normal rats (kept at 28 degrees C) or
      of HET-exposed rats. Atropine (5 mg/kg, i.p.) abolished the hyperthermic effect
      of bicuculline in normal and HET-exposed rats. The BT of normal and HET-exposed
      rat was increased with morphine (1 mg/kg, i.p.) and was reduced with naloxone (1
      mg/kg, i.p.). Bicuculline or physostigmine-induced rise in BT of HET-exposed rats
      was potentiated following cotreatment of physostigmine with morphine. Atropine
      induced hypothermia was abolished due to the cotreatment of atropine with
      morphine with physostigmine but was attenuated with atropine. In normal rats
      (kept at 28 degrees C), only atropine attenuated (morphine + bicuculline)-induced
      hyperthermia. L-Dopa + carbidopa or haloperidol did not significantly affect the
      BT of rats under similar conditions. These results suggest that short-term (2 h)
      exposure to HET activates the opioidergic neuron, which activates cholinergic
      activity through the inhibition of GABAergic system and, thus, enhances the BT.

PMID- 7501683
TI  - Tegmental pedunculopontine nucleus lesions do not block cocaine reward.
AB  - Previous studies have implicated the tegmental pedunculopontine (TPP) nucleus in
      mediating the rewarding effects of opiates, food, and amphetamine, provided that
      animals are not in aversive motivational states induced by food--or drug-
      withdrawal. We wondered if bilateral TPP lesions could block the reinforcing
      effects of systemic cocaine in a place conditioning paradigm. Both lesioned and
      sham animals acquired cocaine place preferences. TPP-lesioned animals
      subsequently failed to acquire place preferences when conditioned with morphine,
      replicating previous data with TPP lesions. It is possible that our cocaine place
      conditioning protocol induced aversions during drug withdrawal, thus explaining
      the inability of TPP lesions to block conditioning. We looked for place aversions
      by conditioning animals at various times postinjection of cocaine. At no time
      point following drug withdrawal from cocaine were significant conditioned
      aversions observed. Cocaine's systemic motivational effects are mediated by a
      substrate separate from the TPP substrate underlying the rewarding effects of
      opiates, food, and amphetamine.

PMID- 7501684
TI  - Cytosolic calcium responses to extracellular adenosine 5',5" '-P1,P4
      tetraphosphate in PC12 cells.
AB  - Binding of adenosine 5',5" '-P1,P4-tetraphosphate (Ap4A) to a purinoceptor on
      nerve growth factor-differentiated (NGF) pheochromacytoma (PC12) cells modulated
      cytosolic Ca2+ levels. Both Ap4A and ATP elicited an influx of extracellular
      Ca2+, but both the sensitivity of the response and the flux profile were
      different. Preincubation of the PC12 cells with the compounds adenosine 5'-0-(2
      thio)diphosphate (ADP-beta-S) and periodate-oxidized ATP had differential effects
      upon the Ap4A and ATP-induced response. These results indicate that Ap4A and ATP
      were either interacting with distinct purinoceptor subclasses or with the same
      purinoceptor with differing affinities. Simultaneous depolarization and
      application of either Ap4A or ATP to the PC12 cells induced an additive effect on
      the calcium flux. Preincubation with verapamil negated the effects of
      depolarization without significantly modifying the ligand-elicited Ca2+ fluxes,
      suggesting the presence of Ap4A ligand-gated channels that may function as
      modulators of PC12 cell function.

PMID- 7501685
TI  - Liver alcohol dehydrogenase activity and ethanol levels during chronic ethanol
      intake in pregnant rats and their offspring.
AB  - The effects of chronic alcohol intake on the ethanol levels in body fluids
      (blood, amniotic fluid, and fetal intragastric content), hepatic alcohol
      dehydrogenase (ADH) activity, isoenzyme distribution, and hepatic zinc levels
      were studied in pregnant rats at term (19 and 21 days), in their offspring at
      fetal, perinatal, and weaned stages, and in adult virgin rats. Three experimental
      groups were studied: 1) the alcohol group received ethanol in drinking water
      (from 10% to 25% over 2 months), 2) the fibre diet group was undernourished on a
      hypocaloric diet, to assess the effects of malnutrition associated with chronic
      alcohol intake, and 3) the control group received no alcohol and normal diet. A
      gradient of increasing ethanol concentrations was found in fetal blood, amniotic
      fluid, and fetal intragastric contents with respect to maternal blood. A decrease
      in ADH activity was found in alcohol-consuming pregnant rats compared to
      controls. This was related neither to liver ADH isoenzyme distribution nor to
      changes in hepatic zinc levels. Chronic alcohol consumption in pregnant rats
      produced high ethanol accumulation in fetal fluids and changes in the liver ADH
      activity depending on the physiological situation (pregnancy, development, virgin
      state).

PMID- 7501687
TI  - Derivatives of 3-digitoxigenone amidinohydrazone: synthesis and effect on the
      digitalis receptor of several species. Part 7: Compounds with positive inotropic
      activity.
AB  - 2-Digitoxigenone amidinohydrazone (1), a compound with known digitalis-like
      activity, and Schiff bases 2-11 of 3-digitoxigenone were synthesized and tested
      pharmacologically in order to further determine possible structural requirements
      at the 3-position of digitalis compounds. The inotropic activity was screened
      using guinea-pig atria, and the interaction with the digitalis receptor was
      further examined using [3H]ouabain binding to cardiac membranes from guinea pig,
      rat, pit and man. All compounds revealed activities intermediate between 3
      digitoxigenone and ouabain, and the potency of the derivatives covered
      approximately one order of magnitude. The absolute potency varied among species,
      but the rank order of potency was rather similar, yielding good correlations
      between species. This indicates no pronounced preference of these compounds for a
      particular (Na+/K+)-ATPase isoform of any of the species studied.

PMID- 7501686
TI  - Strategies and recent technologies in drug discovery.
AB  - In the last years, the paradigms of drug research changed significantly. New
      technologies were developed, in several different fields. Combinatorial chemistry
      and high-throughput screening increase our chances to find new lead structures,
      with less effort than by dedicated syntheses. Gene technology, in addition to
      providing therapeutically useful proteins, significantly contributes to rational
      drug design. The primary structure of a protein can be derived from the DNA
      sequence of the corresponding gene. Its relevance for a certain disease is
      investigated in transgenic animals. Expression of the protein in bacteria or in
      cell culture produces material for screening systems and for 3D structure
      determination by protein crystallography. NMR techniques, or electron cryo
      microscopy. Structure-based and computer-aided design methods are applied to
      optimize lead structures with the least effort. A serious problem in the
      application of such techniques is their limitation to ligand-protein
      interactions. For the design of a therapeutically useful drug, also absorption,
      distribution, metabolism and elimination have to be considered. QSAR methods help
      in this respect. Scope and limitations of the new technologies are discussed in
      the context of conventional approaches in drug discovery.

PMID- 7501688
TI  - Synthesis and cytotoxic evaluation of some Mannich bases of alicyclic ketones.
AB  - A number of Mannich bases of alicyclic ketones containing one and two basic
      centres were prepared in order to evaluate the theory of sequential cytotoxicity
      and develop structure-activity relationships in these series of compounds. The
      compounds were evaluated in vitro against murine P388 D1 lymphocytic leukemia
      cells. The data generated supported the theory of sequential cytotoxicity and in
      general, compounds containing alicyclic rings of five and six carbon atoms
      possessed greater activity than the corresponding dodecyl analogues. Those
      Mannich bases containing dialkylamino groups were associated with greater
      cytotoxicity than related compounds possessing a basic heterocycle. Calculations
      of the atomic charges of the enone groups from selected compounds afforded some
      rationalization for the cytotoxic screening results.

PMID- 7501689
TI  - [Bis((2,4-dioxo-1,2,3,4-tetrahydroquinazolin-3-yl)alkyl)disulfane and 3
      (mercaptoalkyl)quinazolin-2,4(1H,3H)-dione: synthesis by ring transformation and
      antiviral activity. 42. Heterocyclic azines with heteroatoms in the 1- and 3-
      positions].
AB  - Reaction of N-(sulfonyloxy)phtalimide derivatives 1, 2, with cystamine and
      homocystamine, respectively, affords bis[2,4-dioxol-1,2,3,4-tetra-hydroquinazolin
      3-yl)alkyl] disulfanes [sequence: see text] 3, which could be reduced to 3
      (mercaptoalkyl)quinazoline-2,4(1H,3H)-diones. 5. (3-(2-Mercaptoethyl)quinazoline
      2,4(1H,3H)-dione (5a) was also obtained in a one-pot reaction from 1 or 2 and
      cysteamine. 2-Ethoxy-4H-3,1-benzoxazin-4-ones 4a-c were converted with cysteamine
      to 3-(mercaptoethyl)quinazoline-2,4-diones 5a-c by a new ringtransformation
      reaction. 3-(2-Mercaptoethyl)quinazoline-2,4(1H,3H)dione (5a) and the
      corresponding disulfane 3a were evaluated for antiviral activity in vitro.
      Compounds 3a and 5a showed significant antiviral activity against some DNA- and
      RNA-viruses (vaccinia-, herpes simplex virus type 1; influenza A virus) at
      concentrations that were nontoxic to the host cell cultures.

PMID- 7501690
TI  - [Thieno(2',3':3,4)pyrazolo(1,5-a)pyrimidines and -triazines: synthesis of a novel
      ring system].
AB  - The novel tricyclic ring systems 14 can be prepared by reaction of
      thienopyrazoles 5 with 1,3-dielectrophiles, such as acetylacetone,
      dibenzoylmethane or 1,2,4-dithiazole 8. An other synthetic route for the
      preparation of the tricyclic systems, based on the pyrazoloazines 13, was
      investigated. The compounds 5 and 14 were tested for antiulcer activity.

PMID- 7501691
TI  - Synthesis and evaluation of N,N-di-n-propyl-5,6,7,8-tetrahydro-1 H
      benz[f]benzimidazol-6-yl-amine and related congeners as dopaminergic ligands.
AB  - Four semirigid dopaminergic biosiosteres (N,N-di-n-propyl-5,6,7,8-tetrahydro-1 H
      benz[f]benzimidazol-6-yl-amine [sequence: see text] and three related congeners)
      were synthesized and chemically characterized. The affinity and selectivity of
      these compounds for D-1 and D-2 classes of the dopamine receptor were determined
      in competition binding experiments using synaptosomal membranes of the bovine
      caudate nuclei and [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2
      selective) as radioligands. None of the four compounds tested expressed
      significant affinity for D-1 receptors and all of them competed moderately with
      [3H]spiperone binding to D-2 receptors under conditions that prevented
      radioligand binding to serotonin 5HT2 receptors. Some aspects of structure
      affinity relationship for this class of dopaminergic ligands are discussed.

PMID- 7501692
TI  - Evaluation of acrodontiolamide, a chlorinated compound produced by Acrodontium
      salmoneum de Hoog for cytotoxicity and antimicrobial activity.
AB  - A new antifungal compound has been isolated from the culture medium of
      Acrodontium salmoneum de Hoog. Its structure was previously elucidated and was
      named acrodontiolamide. However, this compound is not characteristically produced
      by the genus Acrodontium, it is rather a feature of one isolate of A. Salmoneum
      coming from the soil of the grotto of La Pierre Saint Martin (France).
      Production, purification, cytotoxicity and antimicrobial activities of
      acrodontiolamide are described. Concerning microorganisms, inhibitory activity
      seems to be specifically restricted to phytopathogenic and entomapathogenic
      fungi. Acrodontiolamide is not cytotoxic to either normal human cultured cells or
      tumor cells.

PMID- 7501693
TI  - Microemulsions containing local anaesthetics. Part 6: Influence of microemulsion
      vehicle on in vivo effect of pentacaine.

PMID- 7501694
TI  - Pharmacokinetics of calcitonin in rats with experimental osteoporosis.

PMID- 7501695
TI  - The kinetics of alkaline hydrolysis of the new potential antiarrhythmic,
      substance H + B, in the presence of beta-cyclodextrin.

PMID- 7501696
TI  - The hydrolytic activity of microsomal esterases: organ-dependence and species
      variability.

PMID- 7501697
TI  - Isolation and in vitro antibacterial screening of a tricarboxylic acid anhydride
      from Penicillium sp.

PMID- 7501698
TI  - Paroxetine in the elderly: a comparative meta-analysis against standard
      antidepressant pharmacotherapy.
AB  - In a meta-analysis of ten studies in elderly patients, paroxetine (n = 387) was
      as effective an antidepressant as active controls (amitriptyline n = 110;
      clomipramine n = 109; doxepin n = 102; mianserin n = 28). The change over 5-6
      weeks of therapy, on the Hamilton Depression Rating Scale, was significantly
      better with paroxetine compared with active controls. A similar advantage was
      seen when the responder rate was considered. Adverse events were less frequent
      and less severe with paroxetine treatment, especially anticholinergic adverse
      events. Paroxetine was effective in treating anxiety symptoms associated with
      depression, yet caused significantly less sedation compared with active controls.
      There was little difference in the overall safety profiles seen between the
      paroxetine and active control groups. However, data are available indicating
      reduced cardiotoxicity for paroxetine and a beneficial effect on suicidal
      thoughts. Overall, the results indicate paroxetine is an alternative first-line
      therapy to these older antidepressants and should be considered when treating
      elderly patients.

PMID- 7501699
TI  - Embryotoxicity of free and liposome-encapsulated taxol in the chick.
AB  - Taxol, an inhibitor of microtubule disaggregation, is used in the therapy of
      breast, ovarian, and other human malignancies. The toxicity of taxol
      administration is due in part to the polyoxyethylated castor oil (Cremaphor)
      vehicle in which it is administered; taxol embryotoxicity appears also to be
      partially attributable to vehicle toxicity. Liposome encapsulation is a novel
      vehicle for drug administration. The administration of taxol encapsulated in
      liposomes was evaluated in the chick embryo. Albumen injections of taxol doses up
      to 30 micrograms/egg were used to characterize dose-response curves for free and
      liposome-encapsulated taxol, compared to liposome-only and saline-injected
      control eggs. Sixty percent embryotoxicity (death or malformation) occurred with
      taxol doses of 1.5 micrograms/egg. A 20-fold higher dose was necessary to produce
      the same degree of toxicity with liposome-encapsulated taxol. Curve-fitting
      equations were used to estimate median effective doses (ED50s) and slope
      functions of the dose response curves. The ED50 for taxol was more than an order
      of magnitude lower than that for liposome-encapsulated taxol. Estimated slope
      functions for the two dosage forms of taxol were the same, suggesting similar
      mechanisms of toxicity. The toxicity of liposomes alone was low.

PMID- 7501700
TI  - Monophosphoryl lipid A preserves myocardial contractile function following
      multiple, brief periods of coronary occlusion in dogs.
AB  - The effects of a 1- or 24-hour pretreatment regimen with monophosphoryl lipid A
      (MLA, 35 micrograms/kg i.v.) on myocardial stunning produced by repetitive
      coronary occlusions were studied in barbital-anesthetized dogs. Regional segment
      function (%SS) and myocardial blood flow were measured by sonomicrometry and the
      radioactive microsphere technique, respectively. In controls, six 5-min periods
      of coronary occlusion interpersed with 10-min periods of reperfusion and
      ultimately followed by 2 h of reperfusion produced regional segment dysfunction.
      Pretreatment with MLA for 1 h prior to the first occlusion period had no effect
      on %SS, however, pretreatment with MLA 24 h prior to the first occlusion period
      resulted in a significant (p < 0.05) improvement in the recovery of %SS at all
      reperfusion periods as compared to the control group. In addition, segment
      dysfunction during each occlusion period was significantly less severe in animals
      receiving a 24-hour pretreatment with MLA as compared to the controls. These
      results are the first to demonstrate that MLA, a lipid A derivative of endotoxin,
      preserves contractile function of ischemic myocardium in an in vivo canine model
      and that its cardio-protection is time dependent.

PMID- 7501701
TI  - Effect of high lipid diet and allopurinol on the development of experimentally
      induced arthritis in rats.
AB  - Male albino rats were fed a high lipid diet for 5 consecutive weeks. We studied
      the development of paw inflammation after an injection with Freund's complete
      adjuvant. Increasing the lipid content of the diet significantly increased the
      rate of paw inflammation. Also the effect on this process of oral administration
      of a xanthine oxidase inhibitor (allopurinol, 50 mg/kg) for 15 consecutive days
      was studied. Results indicated that inflammation was significantly inhibited by
      allopurinol.

PMID- 7501702
TI  - Carvedilol, a new beta-adrenoreceptor blocker antihypertensive drug, protects
      against free-radical-induced endothelial dysfunction.
AB  - We tested the ability of carvedilol, an antihypertensive beta-adrenoreceptor
      antagonist with antioxidant properties, to protect rat aorta rings from free
      radical-induced endothelial cell (EC) dysfunction. Rings were exposed to the
      superoxide generator pyrogallol. Vascular function of intact rings was assessed
      by observing acetylcholine (ACh)-induced vasorelaxation following submaximal
      contraction by U-46619. Function of rings denuded of ECs was assessed by
      observing S-nitroso-N-acetylpenicillamine (SNAP)-induced vasorelaxation following
      submaximal contraction by U-46619. Carvedilol exerted a significant protective
      effect against pyrogallol-induced vasoconstriction (17.1 +/- 4.8 vs. 31.9 +/-
      5.4% for vehicle, p < 0.05). Carvedilol also demonstrated significant protection
      against pyrogallol-induced endothelium dysfunction, enhancing vasorelaxation to
      1,000 nmol/l ACh (73 +/- 3.9 vs. 48 +/- 3.0% vehicle, p < 0.01). These protective
      effects were not seen with propanolol, a pure beta-receptor antagonist.
      Carvedilol mixed with pyrogallol and SNAP preserved SNAP-induced vasorelaxation
      in rings denuded of ECs (80.4 +/- 5.3 vs. 63.7 +/- 4.8% control, p < 0.05).
      Carvedilol appears to protect vascular function by scavenging free radicals and
      enhancing the effects of NO.

PMID- 7501703
TI  - DQ-2511, having an antiulcer action, elicits vasodilation through an increase in
      cyclic GMP contents in rat arteries.
AB  - It has been reported that 3-(([2-(3,4
      dimethoxyphenyl)ethyl]carbamoyl)methyl)amino-N-methylbenz amide (DQ-2511:
      ecabapide) effectively increases gastric mucosal blood flow in rats, suggesting
      that this property may contribute to the antiulcer activity. To clarify the
      mechanisms underlying the increase in gastric mucosal blood flow, we investigated
      the dilator response of rat isolated thoracic aorta, mesenteric artery and celiac
      artery smooth muscle preparations to DQ-2511. This compound prevented
      noradrenaline-induced contraction in both the presence and absence of endothelium
      in the arterial specimen, and it (0.01-1 mM) inhibited these contractions induced
      by noradrenaline in all tissues in a concentration-dependent manner. This
      inhibitory effect of DQ-2511 was most evident in the celiac artery. The dilator
      response to DQ-2511 (0.1 mM) was abolished after pretreatment with methylene blue
      (3 microM), a guanylate cyclase inhibitor. Under the same conditions, methylene
      blue inhibited the dilator response to acetylcholine (1 microM), but not that to
      papaverine (10 microM). Furthermore, when DQ-2511 (0.01-1 mM) was incubated with
      the arterial preparations, this compound increased cyclic GMP content in segments
      in a concentration-dependent manner. These findings demonstrate that the
      vasodilation induced by DQ-2511 is independent of the endothelium and is related
      to the augmentation of intracellular cyclic GMP content, which may consequently
      contribute to the increased gastric mucosal blood flow.

PMID- 7501704
TI  - Calcium-induced platelet aggregation in washed platelets from guinea pigs.
AB  - The present study investigated the effects of extracellular calcium on washed
      platelets of guinea pigs, rabbits, rats and humans. CaCl2 without agonists
      induced platelet aggregation in guinea pigs and rabbits, but not in rats or
      humans. CaCl2 increased platelet [Ca2+]i in Fura-2-loaded guinea pig platelets.
      Calcium-induced platelet aggregation was inhibited by W-7 (a calmodulin
      antagonist), aspirin, indomethacin, TMB-8 (an inhibitor of intracellular Ca2+
      release) and also nicardipine (a calcium antagonist). These data suggest that
      CaCl2-induced platelet aggregation is mediated by calmodulin, cyclooxygenase and
      other, as yet unknown, mechanisms.

PMID- 7501705
TI  - Effect of magnesium ions on rabbit detrusor contractility and intracellular free
      calcium.
AB  - Magnesium (Mg2+) is one of the most abundant ions in the body. In the human body,
      Mg2+ plays important roles including cofactors in many crucial enzyme systems,
      especially those involving energy transfer, storage and utilization. Alteration
      of the concentration of Mg2+ may cause neuromuscular hyperactivity, psychiatric
      disturbances, calcium/potassium abnormalities, and overactivity of cardiac
      muscle. Most information on the effect of Mg2+ on muscle contraction has been
      obtained from studies on cardiac, skeletal, and vascular muscle; much less is
      known about the effect of Mg2+ in other smooth muscle systems. In the current
      study, we investigated the effect of Mg2+ on the contraction and intracellular
      free calcium of rabbit urinary bladder detrusor muscle in response to carbachol
      and transmural field stimulation (FS). The results can be summarized as follows:
      (1) Reduction of the concentration of magnesium [Mg2+] from normal Tyrode's
      solution enhanced the spontaneous basal activity, whereas addition of Mg2+
      gradually abolished this spontaneous activity. (2) Muscle contraction induced by
      FS or carbachol was enhanced in Mg(2+)-free Tyrode's solution. Addition of Mg2+
      inhibited the response to both forms of stimulation in a dose-dependent manner.
      (3) Inhibitory effects of Mg2+ were potentiated when the Ca2+ concentration in
      the Tyrode's solution was reduced to 0.6 mM, whereas increasing the extracellular
      concentration of Ca2+ (5.4 mM) reduced the inhibitory effects of Mg2+. (4) Using
      FURA-2 to monitor intracellular free calcium simultaneous with contractile
      tension, we demonstrated that the alterations in the contractile responses
      observed at different concentrations of extracellular Mg2+ correlated with
      similar changes in intracellular free calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501706
TI  - Pharmacokinetics of wood creosote: glucuronic acid and sulfate conjugation of
      phenolic compounds.
AB  - Wood creosote, principally a mixture of non-, alkyl- and/or alkoxy-substituted
      phenolic compounds, was orally administered to adult male volunteers to determine
      its metabolites and pharmacokinetic parameters. After a 133-mg single dose, its
      major constituents (i.e. phenol 15 mg, guaiacol 32 mg, p-cresol 18 mg and creosol
      24 mg) were found in peripheral venous blood and urine, mostly as glucuronic acid
      and, except for creosol, as sulfate conjugates. Low concentrations of
      unconjugated phenols were also detected. The metabolites in the serum started to
      increase 15 min after the dose, and they reached their maximum concentrations 30
      min after administration. The maximum concentrations of glucuronides were 0.18 +/
      0.07, 0.91 +/- 0.38, 0.33 +/- 0.18 and 0.47 +/- 0.23 mg/l; those of sulfates
      were 0.16 +/- 0.06, 0.22 +/- 0.09, 0.17 +/- 0.07 and < 0.04 mg/l for phenol,
      guaiacol, p-cresol and creosol, respectively. The 24-hour urinary recoveries of
      the sum of each compound and its metabolites were 75 +/- 35, 45 +/- 36, 103 +/-
      51 and 74 +/- 36%, in the above order. The presence of guaiacol glucuronide in
      blood and urine was directly verified by its isolation and structure analyses.

PMID- 7501707
TI  - Initial health status of patients at outpatient physical therapy clinics.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to characterize the health
      status of individuals upon initiation of treatment in outpatient physical therapy
      clinics. SUBJECTS: Six outpatient clinical sites participated in the study. Three
      clinics were hospital based, and three clinics were privately owned by physical
      therapists. Patients who were referred with muscular, skeletal, or peripheral
      nerve involvement and who were not postoperative were included in the study.
      METHODS: One hundred nine patients completed the SF-36 health status
      questionnaire, which assessed eight health concepts: physical function, role
      physical (ie, limitations in role functioning such as duties in the home or at
      work due to physical problems), bodily pain, vitality, social function, role
      emotional (ie, limitations in role functioning due to emotional problems), mental
      health, and general health. RESULTS: Patients referred for treatment to hospital
      based or privately owned clinics had similar ages and diagnoses. No differences
      in health status were found between patients to be treated at hospital-based
      clinics and those to be treated at privately owned clinics, or between male and
      female patients. Only physical functioning scores were lower in patients with
      lower-quarter (lumbar or lower-extremity) disorders versus patients with upper
      quarter (cervical or upper-extremity) disorders. All health concept scores,
      except general health, were found to differ from previously published normative
      data on the US population. CONCLUSION AND DISCUSSION: A subgroup of patients
      seeking outpatient physical therapy had lower health concept scores than did the
      general population in not only the physical domain of health but also the
      psychological and social domains. These data reinforce the concept that physical
      impairment interacts with the emotional and social aspects of health. In
      addition, the health concept scores of our sample as compared with other patient
      groups who have responded to the SF-36 revealed some similarities and some marked
      differences. The results suggest that these types of data will provide practicing
      clinicians, as well as third-party payers and policy-makers, with a greater
      understanding of the severity of the patient's condition. Because the SF-36
      provides information on health not routinely assessed by physical therapists, it
      may be a useful screening tool. [Mossberg KA, McFarland C. Initial health status
      of patients at outpatient physical therapy clinics.

PMID- 7501708
TI  - Physical therapist assistants' perceptions of the documented roles of the
      physical therapist assistant.
AB  - BACKGROUND AND PURPOSE: This study investigated physical therapist assistants'
      (PTAs) perceptions of the documented roles of PTAs and compared those perceptions
      with those of physical therapists from a previous study. SUBJECTS AND METHODS: A
      questionnaire that described 79 physical therapy activities was distributed to a
      sample (n = 400) of PTAs derived from the American Physical Therapy Association
      membership. The response rate was 56% (n = 225). Respondents indicated whether
      each activity was included in the documentation describing PTA roles.
      Discriminant analyses were used to determine whether demographic factors
      predicted the pattern of responses. In addition, meta-analytic techniques were
      used to determine whether PTA responses were different from those of physical
      therapists gathered previously. RESULTS: The greatest agreement of PTA opinions
      with published guidelines occurred for treatment implementation activities, and
      the lowest level of agreement occurred for items designated as administrative
      activities. Responses of PTAs were different from those of physical therapists on
      21 of the 79 activities. The greatest number of these differences occurred for
      evaluative functions (n = 9). Physical therapist assistants' perceptions of
      documented PTA roles were generally less consistent with published guidelines
      than were those of physical therapists. CONCLUSION AND DISCUSSION: Physical
      therapist assistants' perceptions of the roles of the PTA were, for some
      activities, not consistent with written guidelines. Using the data provided in
      this study, discussions to revise the documentation of the scope of PTA practice
      may focus on those activities for which disagreement between PTAs and physical
      therapists exists and for which opinions differ markedly from published
      guidelines. [Robinson AJ, DePalma MT, McCall M. Physical therapist assistants'
      perceptions of the documented roles of the physical therapist assistant.

PMID- 7501709
TI  - Pelvic-floor rehabilitation, Part 1: Comparison of two surface electrode
      placements during stimulation of the pelvic-floor musculature in women who are
      continent using bipolar interferential currents.
AB  - BACKGROUND AND PURPOSE: Electrical stimulation of the pelvic floor is used as an
      adjunct in the conservative treatment of urinary incontinence. No consensus
      exists, however, regarding electrode placements for optimal stimulation of the
      pelvic-floor musculature. The purpose of this study was to compare two different
      bipolar electrode placements, one suggested by Laycock and Green (L2) the other
      by Dumoulin (D2), during electrical stimulation with interferential currents of
      the pelvic-floor musculature in continent women, using a two-group crossover
      design. SUBJECTS: Ten continent female volunteers, ranging in age from 20 to 39
      years (mean = 27.3, SD = 5.6), were randomly assigned to one of two study groups.
      METHODS: Each study group received neuromuscular electrical stimulation (NMES) of
      the pelvic-floor musculature using both electrode placements, the order of
      application being reversed for each group. Force of contraction was measured as
      pressure (in centimeters of water [cm H2O]) exerted on a vaginal pressure probe
      attached to a manometer. Data were analyzed using a two-way, mixed-model analysis
      of variance. RESULTS: No difference in pressure was observed between the two
      electrode placements. Differences in current amplitude were observed, with the D2
      electrode placement requiring less current amplitude to produce a maximum
      recorded pressure on the manometer. Subjective assessment by the subjects
      revealed a preference for the D2 electrode placement (7 of 10 subjects).
      CONCLUSION AND DISCUSSION: The lower current amplitudes required with the D2
      placement to obtain recordings comparable to those obtained with the L2 technique
      suggest a more comfortable stimulation of the pelvic-floor muscles. The lower
      current amplitudes required also suggest that greater increases in pressure might
      be obtained with the D2 placement by increasing the current amplitude while
      remaining within the comfort threshold. These results will help to define
      treatment guidelines for a planned clinical study investigating the effects of
      NMES and exercise in the treatment of urinary stress incontinence in women
      postpartum. [Dumoulin C, Seaborne DE, Quirion-DeGirardi C, Sullivan SJ. Pelvic
      floor rehabilitation, part 1: comparison of two surface electrode placements
      during stimulation of the pelvic-floor musculature in women who are continent
      using bipolar interferential currents.

PMID- 7501710
TI  - Pelvic-floor rehabilitation, Part 2: Pelvic-floor reeducation with interferential
      currents and exercise in the treatment of genuine stress incontinence in
      postpartum women--a cohort study.
AB  - BACKGROUND AND PURPOSE: This descriptive cohort study investigated a physical
      therapy program of pelvic-floor neuromuscular electrostimulation (NMES) combined
      with exercises, with the aim of developing a simple, inexpensive, and
      conservative treatment for postpartum genuine stress incontinence (GSI).
      SUBJECTS: Eight female subjects with urodynamically established GSI persisting
      more than 3 months after delivery participated in the study. The subjects ranged
      in age from 24 to 37 years (X = 32, SD = 4.2). METHODS: This was a descriptive
      multiple-subject cohort study. Each subject received a total of nine treatment
      sessions during 3 consecutive weeks, consisting of two 15-minute sessions of NMES
      followed by a 15-minute pelvic-floor muscle exercise program. Patients also
      practiced daily pelvic-floor exercises during the 3-week treatment period. The
      treatment intervention was measured using three separate variables. Maximum
      muscle contractions (pretraining, during training, and post-training) were
      measured indirectly as pressure, using perineometry. Urine loss pretraining and
      posttraining was measured by means of a Pad test. Self-reported frequency of
      incontinence was recorded daily throughout the period of the study, using a
      diary. Data were analyzed using a one-way repeated-measures analysis of variance
      (ANOVA), a Wilcoxon signed-ranks test, and a Friedman two-way ANOVA by ranks.
      RESULTS: The results indicated that maximum pressure generated by pelvic-floor
      contractions was greater and both the quantity of urine loss and the frequency of
      incontinence were lower following the implementation of the physical therapy
      program. Five subjects became continent, and three others improved. A follow-up
      survey 1 year later confirmed the consistency of these results. CONCLUSION AND
      DISCUSSION: The results suggest that the proposed physical therapy program may
      influence postpartum GSI. Further studies are needed to validate this simple,
      inexpensive, and conservative physical therapy protocol. [Dumoulin C, Seaborne
      DE, Quirion-DeGirardi C, Sullivan SJ. Pelvic-floor rehabilitation, part 2: pelvic
      floor reeducation with interferential currents and exercise in the treatment of
      genuine stress incontinence in postpartum women--a cohort study.

PMID- 7501711
TI  - Interrater reliability of auscultation of breath sounds among physical
      therapists.
AB  - BACKGROUND AND PURPOSE: Although auscultation is routinely used in the assessment
      of respiratory status, the ability of the rater to accurately and consistently
      identify lung sounds has been questioned. The literature on this issue is sparse
      and has focused on reliability of auscultation of tape-recorded rather than in
      vivo lung sounds. The purposes of this study were to determine the interrater
      reliability of physical therapists in the direct auscultation of lung sounds
      based on their clinical experience in chest physical therapy and to determine
      whether the adoption of standardized nomenclature and education on proper
      technique and interpretation affects reliability. SUBJECTS AND METHODS: A group
      of 57 registered physical therapists were stratified by clinical experience into
      four groups. Sixteen therapists (ie, 4 in each stratum) were randomly chosen
      using a random number table. The following criteria were developed to delineate
      clinical experience. Group 1 subjects were senior chest physical therapists with
      at least 5 years of experience in this area of practice. Group 2 subjects were
      experienced therapists who had a minimum of 2 years of experience in chest
      physical therapy and were currently practicing in this area. Group 3 subjects
      were experienced physical therapists in other areas who were also practicing in
      chest physical therapy on occasional weekend service. Group 4 subjects were new
      graduates. Ten patients were evaluated by each group of 4 physical therapists
      using a teaching stethoscope with one diaphragm/bell and four pairs of earpieces.
      The education session consisted of discussion of the adoption of standardized
      nomenclature and education on proper technique and interpretation of
      auscultation. Interrater reliability was assessed before and after the education
      session using kappa (kappa) values. Comparisons were made between kappa values
      before and after the education session to determine the effect of education and
      between groups to determine the effect of clinical experience. RESULTS: The kappa
      values before the education session were low, indicating poor reliability in
      detecting specific abnormal sounds (kappa = -.02-.59). Group 1 (seniors in
      respiratory therapy) and group 4 (new graduates) demonstrated the greatest
      reliability levels. The lowest kappa values were observed for detecting and
      categorizing the quality of breath sounds (normal, absent, bronchial, or
      decreased) (kappa = -.02-.25). Following the education session, there was a
      general improvement in reliability (kappa = -.30-.77), especially for group 3
      (specialists in other areas). The most improvement was noted for the detection of
      the quality of breath sounds (kappa = .08-.50). CONCLUSION AND DISCUSSION:
      Reliability of auscultation was poor to fair, in general, before the education
      session. There was a definite improvement in reliability after the education
      session. There was no clear effect of clinical experience on reliability, and the
      agreement among observers appeared to depend on the abnormal lung sound present.
      Limitations of this study and recommendations for future research are discussed.
      [Brooks D, Thomas J. Interrater reliability of auscultation of breath sounds
      among physical therapists.

PMID- 7501712
TI  - Early family experiences and helping behaviors of physical therapists.
AB  - BACKGROUND AND PURPOSE: Ineffective or excessive helping behavior may encourage
      helpee dependence and overextension of helper resources. Early family experiences
      and perceptions of the helpee's situation both contribute to the expression of
      helping behavior in health professionals. The purpose of this study was to
      determine how early family experiences and variations in perceived patient
      responsibility influence physical therapist helping behavior. SUBJECTS AND
      METHODS: Five hundred physical therapists were surveyed by mail, resulting in a
      final sample of 221 (44%) respondents who completed the Family of Origin Scale
      (FOS), measuring the nature of their early family experiences, and a Helping
      Questionnaire, measuring their helping behavior, perceptions of replaceability,
      and feelings of compassion for four hypothetical patients. The four patients
      represented Brickman's models of helping and coping, varying in high and low
      responsibility for the problem and high and low responsibility for the solution
      to the problem. RESULTS: Subjects who scored in the dysfunctional or neutral
      ranges on the FOS had lower scores on their willingness to help and feelings of
      compassion than did subjects who scored in the functional range on the FOS.
      Regardless of early family experiences, subjects' scores were higher for
      willingness to help and feelings of compassion and lower in their perceptions of
      replaceability for patients who were not thought to be responsible for their
      medical problem (medical and compensatory models). In contrast, subjects' scores
      were lower for their willingness to help and feelings of compassion and higher in
      their perceptions of replaceability when patients were felt to be responsible for
      their medical problem (enlightenment and moral models). CONCLUSION AND
      DISCUSSION: All subjects, regardless of early family experience, showed helping
      responses that linked feelings of compassion with greater tendencies to help.
      Variations in perceived patient responsibility for the medical problem, rather
      than early family experience, appears to be a major determinant in motivating
      both compassion and helping behavior. Thus, helpers may be more likely to
      overextend themselves or create patient dependence when patients are perceived to
      be not responsible for the cause of their problem. [Curtis KA, Davis CM, Trimble
      TK, Papoulidis DK. Early family experiences and helping behaviors of physical
      therapists.

PMID- 7501713
TI  - Benefits of the collaborative model.

PMID- 7501714
TI  - Commitment to clinical education.

PMID- 7501715
TI  - Colonoscopy.
AB  - Colonoscopy is a procedure that more primary care physicians are performing. This
      article has attempted to provide such physicians the basic information needed
      regarding the indications, contraindications, and complications associated with
      colonoscopy. Patient issues such as preparation, education, and consent were also
      discussed.

PMID- 7501717
TI  - Drugs and sedation for colonoscopy.
AB  - Sedation, with or without analgesia, is commonly used for colonoscopy procedures
      in the United States. Prudent drug product selection, careful titration of drug
      dosage to ensure use of the lowest effective dose (Table 1), and vigilant
      monitoring of medicated patients will optimize the value of conscious sedation in
      colonoscopy. When a close patient-physician relationship exists in the primary
      care setting, use of medications only "if needed" during the procedure may be a
      reasonable alternative that can minimize the exposure of patients to sedation
      related side effects. Patient-controlled medication delivery may be one method
      used to address patient variability in the need for sedation.

PMID- 7501716
TI  - Insertion techniques.
AB  - The author provides a systematic and rational approach to the endoscopic
      examination of the colon. Anatomy, instrumentation, and technique are reviewed.
      Attention to completeness of the examination and patient safety is stressed.

PMID- 7501718
TI  - Antibiotic prophylaxis for lower gastrointestinal endoscopy.
AB  - Bacterial endocarditis is a preventable disease in most patients. It is a
      potentially fatal disease if left untreated. This article addresses issues
      related to bacterial endocarditis prophylaxis as related to lower
      gastrointestinal endoscopy and the recommendations of the American Heart
      Association.

PMID- 7501720
TI  - Cleaning and disinfection of lower gastrointestinal endoscopes.
AB  - Cleaning and disinfection are two necessary and equally important steps to
      prevent transmission of infection from patient to patient by the endoscope and
      accessories. There is no evidence that complete sterility is necessary; high
      level disinfection is recommended. Controversy remains as to how "high level"
      this disinfection must be. It is important that these processes not become
      complicated, difficult, or intimidating. They must be efficacious and yet safe
      for the scope as well as for the attending staff. It is strongly recommended that
      the clinician fully understands the cleaning and disinfection steps and not
      inhibit his or her staff's ability to perform them correctly. It is important
      that we use these relatively new and important diagnostic equipment tools to
      improve the health of the public. There are several studies now that suggest that
      screening flexible sigmoidoscopies may be of value in decreasing mortality from
      colonic adenocarcinomas. It is important that we remain focused on our overall
      mission while at the same time "do no harm."

PMID- 7501719
TI  - Colonoscopic biopsy and polypectomy.
AB  - The techniques of biopsy and polypectomy are essential skills for a primary care
      endoscopist because lesions requiring these interventions are common. This
      article reviews common and uncommon lesions, electrosurgical principles,
      traditional, and novel techniques.

PMID- 7501721
TI  - Psychological considerations in colonoscopy.
AB  - In summary, psychological issues around the colonoscopy procedure have not yet
      been fully studied or even formulated. The framework taken here is to consider
      psychological preconditions to disease, psychological barriers to screening, and
      ways to maximize the psychological strength of patients when presenting serious
      diagnoses. Two common themes are present in this review. First, the idea of
      hopelessness and loss of personal control is present throughout the research in
      terms of personality predispositions, decisions to seek care, and outcome of
      disease when present. Physicians need to address the question, what can I do to
      maximize the hopefulness of this person before, during, and after screening? Are
      we encouraging an optimistic perspective in the lives of others? The second theme
      is closely related and that is the critical nature of the patient/physician
      relationship in all stages of health/illness behavior. It is often the positive,
      empathic strength of this relationship that affects patient behavior and
      ultimately the patient's medical outcome. Future research as well as physician
      self-examination and increased knowledge in this area are truly important. It is
      in this way that the procedure of colonoscopy truly becomes part of the total
      patient care.

PMID- 7501722
TI  - Privileges, credentialing, and liability.
AB  - The author describes the real, turbulent, rocky, and political turf road battle
      of obtaining endoscopic privileges and credentialing. Increases in liability
      expected from an expanded practice are also discussed.

PMID- 7501723
TI  - [International cooperative study on mental diseases].

PMID- 7501724
TI  - Genetic heterogeneity of schizophrenia.
AB  - The cumulative evidence from over a century of research overwhelmingly implicates
      genes in the etiology of Schizophrenia. Twin studies consistently find higher
      rates of schizophrenia among cotwins of monozygotic compared with dizygotic twins
      and adoption studies show that familial transmission is mediated by genetic, not
      adoptive relationships. Nevertheless, the hunt for schizophrenia genes with
      molecular genetic technologies has been disappointing. Although the available
      literature suggests that cytogenetic abnormalities cause some cases of
      schizophrenia, these abnormalities must account for only a small fraction of all
      schizophrenia. Attempts to scan the entire genome with DNA markers spaced at
      regular intervals have failed to produce unequivocal linkage findings. Notably,
      several groups have reported findings suggestive of linkage to chromosome 22 and
      other work provides weak evidence of a gene on the sex chromosomes. The search
      for schizophrenia genes has been complicated by its unknown mode of transmission,
      the possibility of phenocopies and genetic heterogeneity.

PMID- 7501725
TI  - [Study on amenities of psychiatric hospitals--special reference to the results of
      questionnaires].

PMID- 7501727
TI  - [Psychoeducation--special reference to social skill training].

PMID- 7501726
TI  - Client movement in Europe: its past, present and future.

PMID- 7501728
TI  - [Symptomatologic characteristics and psychopathology of expression of an "attack
      of altered perception" in schizophrenic patients].
AB  - Eleven patients with schizophrenia who developed an "attack of altered
      perception" are reported and discussed from the viewpoints of the symptomatologic
      characteristics of their mental symptoms, physical symptoms, and drawing
      expression. It was found that the attack appeared in patients with non-paranoid
      schizophrenia as well as in non-schizophrenic patients on major tranquilizers.
      Some patients developed obvious visual and auditory hallucinations, etc. Most
      visual hallucinations were of, or related to, an eye. The hallucinations were
      largely non-schizophrenic organic hallucinations that J. Glatzel recognized as
      "Sinnestauschung", i.e., a false perception from hallucination. Physical
      complications which included extrapyramidal symptoms were observed mainly in the
      eye and its surrounding area in all cases. There were also items in common with
      tardive oculogyric crisis, complicated by mental symptoms, suggesting a close
      relationship between "attack of altered perception" and oculogyric crisis. Non
      verbal, visual inner experiences during the attack had a strong affinity to the
      patient's drawing expression, reflecting a psychopathology of expression. Visual
      illusions, visual hallucinations, sensory distortions and hyperesthesia were
      found to be related to the drawing subject matter, such as eyes, bodies cut into
      pieces, heterochromatism, stains and spots. Such specific drawing expression is
      thought to result from the symptoms of the attack. On the other hand, a
      difference in the attack's ramifications was apparently dependent on whether or
      not the primary disease underlying the attack was schizophrenia. It is presumed
      that schizophrenic patients have a schizophrenia-like expression stamped on their
      mental symptoms, thus paroxysmal symptoms are modified by their schizophrenic
      symptoms and personality. Finally, an "attack of altered perception" as a whole
      is thought to be understandable as a continuum, running from a physical base to
      physical symptoms, mental symptoms (like inner experience) and expression
      activity (like drawing). Schizophrenia may modify the attack but should not be
      considered as the originating cause of the attack.

PMID- 7501729
TI  - Antidepressant responses and changes in visual adaptation after sleep
      deprivation.
AB  - The effects of 1 night of total sleep deprivation on mood state and visual light
      dark adaptation were studied in 15 patients with major depression and nine normal
      comparison subjects. Mood improvements were evident in all but one patient,
      although responders (n = 9) could be easily distinguished from nonresponders (n =
      6). No significant group differences were found in ocular responses before
      treatment. After treatment, however, light-adapted peak corneofundal potentials
      increased in patient responders and decreased in patient nonresponders and normal
      subjects. Moreover, changes in peak values were closely correlated (r = -0.74)
      with changes in scores on the Hamilton Depression Rating Scale. In contrast, dark
      adapted trough potentials did not distinguish between diagnostic groups and were
      not correlated with clinical responses. The results indicate that sleep
      deprivation induces changes in light sensitivity that are proportional to
      improvements in depressive state.

PMID- 7501731
TI  - Antimanic drugs stabilize hamster circadian rhythms.
AB  - The circadian wheel-running rhythm of golden hamsters was monitored during
      chronic oral treatment with four mood-stabilizing drugs in doses relevant for
      treatment of manic-depressive disorder. Carbamazepine and verapamil shortened the
      duration of locomotor activity and improved the stability of the pattern of
      running activity. At comparable doses, valproate had no clear effect on any
      rhythm variable tested. None of these drugs consistently altered the phase of
      light-synchronized running rhythms or the period of the rhythm in constant
      darkness. The results are compared to data showing that lithium, which delays
      entrained phase and lengthens circadian period in hamsters, also shortens
      activity duration and increases the stability of wheel-running rhythms.
      Stabilization of circadian rhythms may be a key action of clinically effective
      mood-stabilizing drugs.

PMID- 7501732
TI  - Observed behavior of patients with seasonal affective disorder and an interviewer
      predicts response to light treatment.
AB  - We investigated whether observable behavior of seasonal affective disorder (SAD)
      patients and an interviewer during an interview before light treatment is related
      to the response to the light treatment. Different observed behavioral elements of
      24 SAD patients and of 2 interviewers, assessed before light treatment, were
      reduced to "behavioral factors." Forward multiple regression analyses were
      applied to investigate whether these factors might predict the response to light
      therapy (3 h of bright light between 09:00 and 12:00 h or between 18:00 and 21:00
      h on 5 consecutive days). In addition, it was investigated whether the
      interviewers' factors could be predicted from the patients' factors. Both
      patients' and interviewers' factors predicted the response to light treatment.
      Response-related factors of patients and interviewers were interrelated. The
      results suggest that behavioral processes may play a role in the mechanisms
      underlying the response to light treatment in SAD. They support the relevance of
      interpersonal theories in seasonal depression.

PMID- 7501733
TI  - The gonadal axis in men with schizophrenia.
AB  - The typical onset of schizophrenia during late adolescence and early adulthood
      has stimulated interest in the potential contribution of hypothalamo-pituitary
      gonadal (HPG) axis abnormalities to this disorder. Previous investigations of
      reproductive hormone function in men with schizophrenia suggest diminished
      activity of the HPG axis. These studies have been hampered, however, by
      methodologic limitations. We have attempted to address these limitations by
      rigorous determination of gonadotropin and gonadal hormone levels, and attention
      to demographic and diagnostic variables. In contrast to prior studies, our
      results indicate that schizophrenic patients do not show statistically
      significant differences from healthy volunteers with respect to luteinizing
      hormone pulsatility, response to gonadotropin-releasing hormone challenge, and
      testosterone secretion. Due to the small number of subjects, however, these
      findings must be regarded as preliminary and warrant further study.

PMID- 7501730
TI  - Affective state dependence of the Tridimensional Personality Questionnaire.
AB  - The authors administered the Tridimensional Personality Questionnaire (TPQ) on
      two occasions separated by more than 1 month to 30 patients with psychotic
      disorders to examine hypothesized relationships between affective symptomatology
      and the TPQ dimension Harm Avoidance. As predicted, changes in Harm Avoidance
      scores demonstrated a robust correlation with changes in depression ratings and a
      less robust association with changes in mania ratings. The TPQ dimensions Novelty
      Seeking and Reward Dependence demonstrated minimal associations with symptom
      measures. This study supports the hypothesis that Harm Avoidance scores are
      strongly associated with depression.

PMID- 7501735
TI  - A seasonal pattern of hospital medication errors in Alaska.
AB  - Specific behavioral consequences of seasonal affective disorder have not been
      closely examined. Length of daylight is evaluated in relation to medication
      errors in a medical center located in the far north. Factors such as numbers of
      patient admissions, discharges, and deaths were controlled with data collected in
      Anchorage, Alaska, over 5 consecutive years, 1985-89. These data revealed that
      58% of all medication errors occurred during the first quarter of the year.
      Medication errors were 1.95 times more likely in December than September. The
      best statistical prediction was for errors associated with levels of darkness 2
      months earlier. There may be not only an impairment of work performance among
      hospital nursing staff that reaches a peak in late winter but, more importantly,
      medication errors appear to follow a pattern that is closely associated with the
      annual cycle of daylight and darkness.

PMID- 7501734
TI  - Cognitive and psychophysiological correlates of positive, negative, and
      disorganized symptoms in the schizophrenia spectrum.
AB  - This study examined the cross-sectional and prospective relationships between
      cognitive and psychophysiological variables and positive, negative, and
      disorganized symptoms in 40 outpatients with diagnoses of schizophrenia or
      schizoaffective disorder. The results indicated that disorganized symptoms were
      related to deficits in auditory and visuomotor attentional processing, increased
      skin conductance orienting response, and lower stress reactivity. Negative
      symptoms were related to reduced resting heart rate, increased stress reactivity,
      and deficits in visuomotor processing. Prospective findings indicated that both
      the cognitive and heart-rate variables might be trait-related aspects of the
      negative symptoms, while the skin conductance, but not the cognitive, variables
      might be trait-related aspects of the disorganized symptoms. Positive symptoms
      were not related to any of the cognitive or psychophysiological variables.

PMID- 7501736
TI  - Cerebrospinal fluid total protein in patients with affective disorders.
AB  - Cerebrospinal fluid (CSF) total protein was evaluated in 240 patients with
      affective disorders and compared with findings in 55 normal comparison subjects.
      Subtype diagnoses were as follows: bipolar I (n = 108, 47 men, 61 women); bipolar
      type II (n = 67, 26 men, 41 women); and unipolar (n = 65, 22 men, 43 women). Men
      had significantly elevated values compared with women. In men with bipolar I
      disorder, mean CSF protein levels were found to be significantly elevated over
      those in normal subjects, with 31.9% above the traditional normal range cutoff of
      45 mg/dl. Moreover, CSF protein levels in male bipolar I patients were found to
      be positively correlated with severity of depression at the time of the lumbar
      puncture and with duration of illness. It thus appears that increased protein
      levels may be associated with illness severity or progression in male patients
      with bipolar I disorder. Although elevated CSF protein is a nonspecific marker of
      cerebral pathology, further search for the potential underlying
      pathophysiological mechanisms related to this finding would now appear to be
      warranted.

PMID- 7501737
TI  - Hypersensitivity to inhalation of carbon dioxide and panic attacks.
AB  - Thirteen healthy subjects with infrequent panic attacks and without agoraphobia
      who did not meet DSM-III-R criteria for panic disorder, 43 patients with panic
      disorder, and 43 healthy control subjects who never experienced panic attacks
      underwent one vital capacity inhalation of 35% CO2. Healthy subjects with
      infrequent panic attacks reacted similarly to patients with panic disorder and
      more strongly than healthy subjects who never experienced panic attacks. The
      results suggest that (a) subjects with sporadic unexpected panic attacks and
      patients with panic disorder belong to the same spectrum of vulnerability and (b)
      CO2 hypersensitivity might be a trait marker of panic attacks rather than of a
      clinical diagnosis of panic disorder.

PMID- 7501738
TI  - Serotonin-stimulated intracellular calcium mobilization in platelets from
      alcoholic men.
AB  - Numerous lines of evidence have suggested a key role for serotonin (5
      hydroxytryptamine, 5HT) pathways in the regulation of alcohol consumption. To
      explore the functioning of the 5HT2 receptor in alcoholism, 5HT-stimulated
      intracellular calcium response was measured in platelets from abstinent alcoholic
      patients and normal comparison subjects. No difference in resting or stimulated
      calcium levels was observed. This finding suggests that 5HT2 receptor function is
      unaffected in non-drinking alcoholic subjects. The previously reported 5HT
      inhibition in actively drinking alcoholic subjects is likely to be a state rather
      than trait marker of alcoholism.

PMID- 7501739
TI  - Motor asymmetry, a neurobiologic abnormality in the major psychoses.
AB  - A century after Kraepelin, clinical scientists still debate whether the major
      functional psychoses, schizophrenia and bipolar illness, are separate disease
      entities or fall on opposite ends of a spectrum of severe psychopathology. In a
      study of control of hand-muscle force, patients with schizophrenia and bipolar
      affective disorder exhibited opposite asymmetries, with greater right-hand
      dyscontrol in schizophrenia, and greater left-hand dyscontrol in bipolar
      disorder. This suggests that there is greater pathological involvement of the
      dominant hemisphere in schizophrenia and of the non-dominant hemisphere in
      bipolar disorder.

PMID- 7501740
TI  - Determinants and consequences of children's coping in the medical setting:
      conceptualization, review, and critique.
AB  - The recent burgeoning of theory and research on how children cope with painful
      medical stressors warrants close scrutiny. The authors examine the prominent
      typologies of coping and the research on child adjustment and outcomes stimulated
      by those typologies. They focus on what researchers know and need to know about
      moderators (characteristics of the child and the environment that influence
      coping and outcome) and mediators (mechanisms linking stress, coping, and
      adjustment). It is argued that important advances can be achieved through efforts
      to (a) conceptualize and study pain and coping within a multidisciplinary
      framework; (b) clearly distinguish among coping responses, goals, and outcomes;
      and (c) replace simplistic conceptualizations with transactional and goodness-of
      fit models.

PMID- 7501741
TI  - Issues in personality as diathesis for depression: the case of sociotropy
      dependency and autonomy-self-criticism.
AB  - A congruency between personality and life stress is assumed to pose a particular
      risk for depression. The authors review relevant research as a way of examining
      broader issues entailed in diathesis-stress models of depression. Topics include
      the identification of distinct personality modes and the differentiation of these
      modes from the phenomena of depression and the influence of the social context.
      Diathesis-stress models face formidable conceptual and methodological challenges.
      More complex models are needed to accommodate the dynamics of a person's life
      course, involvement in significant social contexts, and fluctuations in
      vulnerability to depression. Base rates of key phenomena favor development of
      models of depression recurrence in high-risk samples rather than its onset in the
      general population.

PMID- 7501742
TI  - Facial expressions of emotion: what lies beyond minimal universality?
AB  - This article discusses the controversy over whether attribution (recognition) of
      emotions from facial expressions is universal (P. Ekman, 1994; C. E. Izard, 1994;
      J. A. Russell, 1994). Agreement emerged on various issues. There exists at least
      Minimal Universality (people everywhere can infer something about others from
      their facial behavior). Anger, sadness, and other semantic categories for emotion
      are not pancultural and are not the precise messages conveyed by facial
      expressions. Emotions can occur without facial expressions, and facial
      expressions can occur without emotions. Further evidence is needed to determine
      the relationship between emotion and facial behavior, what determines that
      relationship, how facial behavior is interpreted, and how much the interpretation
      varies with culture and language. Ekman's (1994) objections are answered.

PMID- 7501743
TI  - Regression analyses of counts and rates: Poisson, overdispersed Poisson, and
      negative binomial models.
AB  - The regression models appropriate for counted data have seen little use in
      psychology. This article describes problems that occur when ordinary linear
      regression is used to analyze count data and presents 3 alternative regression
      models. The simplest, the Poisson regression model, is likely to be misleading
      unless restrictive assumptions are met because individual counts are usually more
      variable ("overdispersed") than is implied by the model. This model can be
      modified in 2 ways to accomodate this problem. In the overdispersed model, a
      factor can be estimated that corrects the regression model's inferential
      statistics. In the second alternative, the negative binomial regression model, a
      random term reflecting unexplained between-subject differences is included in the
      regression model. The authors compare the advantages of these approaches.

PMID- 7501744
TI  - Nonlinear models of clinical judgment: Meehl's data revisited.
AB  - Previous attempts to detect nonlinearity in clinical judgments have not succeeded
      because of a lack of good nonlinear models. Much research in this area was based
      on data collected by Paul Meehl, which include clinicians' judgments of mental
      disorder on the basis of Minnesota Multiphasic Personality Inventory profiles. In
      this article, Meehl's data are reanalyzed using several versions of the scatter
      model in which nonlinearity is represented by the within profile scatter(s) of
      the cues. The author finds that these versions give a better fit to the data than
      the linear model. He also finds systematic patterns of nonlinearity that lend
      themselves to psychological interpretation.

PMID- 7501745
TI  - Suicide and homicide among Native Americans: a comment.

PMID- 7501746
TI  - Structural findings regarding the Silencing the Self Scale.
AB  - Principal components factor analysis, based on scores of 363 college women,
      confirmed four subscales of the Silencing the Self Scale; however, 5 items loaded
      differently in the structure of these subscales. Recommendations for scale
      revision and studies with other populations are suggested.

PMID- 7501747
TI  - Listening to Mozart may not enhance performance on the revised Minnesota Paper
      Form Board Test.
AB  - Rauscher, Shaw, and Ky in 1993 found that listening to a Mozart sonata
      temporarily enhanced performance on the spatial reasoning task from the Stanford
      Binet scale. The present study was designed to replicate those results using the
      Revised Minnesota Paper Form Board Test. 30 women and 21 men were randomly
      assigned to one of two conditions. In one condition, subjects listened to a
      Mozart sonata for 10 min., while in the control condition subjects meditated in
      silence for 10 min. Immediately following these manipulations all subjects worked
      on the spatial task, the Revised Minnesota Paper Form Board Test, for 10 minutes.
      After factoring out SAT scores and gender, there was no significant difference in
      the mean test scores for the two groups. The results are discussed in terms of
      Gustafsson's 1984 factor analysis of intellectual abilities in which he
      identified three separate visuospatial factors. The task used here may have had a
      substantially different factor loading than the dependent variable used by
      Rauscher and associates.

PMID- 7501748
TI  - Relationship of eight basic emotions with age, sex, education, satisfaction of
      life needs, and religion.
AB  - Personality scores of Croatian men and women by age, occupation, education,
      satisfaction of life needs, and religion were examined. 842 men and 242 women
      whose mean age was 42 yr. (SD, 8) represented manual labor, clerical work, and
      management. Employees were administered the Emotions Profile Index and a test of
      Life Needs Satisfaction. The Croatian women scored lower on Distrustful and
      Dyscontrol than the Croatian men and higher on Depression and Gregarious. Scores
      on Aggression, Depression, and Gregarious varied across age groups. The
      Reproduction scores of sociable and affectionate were significantly higher for
      managers and persons with university education. The religious employees scored
      higher on Depression than nonreligious persons. The Reproduction scores were
      significantly positively associated with all needs satisfaction scores. The
      Destruction scores (Aggression, Depression) were significantly negatively
      associated with most life needs satisfactions. The present analysis suggests men
      and women from Croatian groups have different personality profiles. Correlations
      of emotional scores with ages, occupations, education, life needs satisfaction,
      and religion could help in modification toward positive emotional dimensions.

PMID- 7501749
TI  - Intelligence and suicide in Ireland and the United Kingdom.

PMID- 7501750
TI  - War and suicide in France, 1850-1913.

PMID- 7501751
TI  - Association of scores for Type A behavior with age, sex, occupation, education,
      life needs satisfaction, smoking, and religion in 1084 employees.
AB  - The associations of Type A or B behavior with age, sex, occupation, education,
      life needs satisfaction, smoking, and religion were studied. 242 women and 842
      men, ages 21 to 64 years, (M age 42 +/- 8 yr.), completed the Bortner scale and
      rated on a 5-point scale their life needs satisfaction. Information on age,
      occupation, education, cigarette smoking, and religion were obtained from each
      subject. Scores for Type A and Type B behavior patterns in different age groups
      were very similar. Scores on Type A behavior were significantly more common in
      women than men. Type A behavior scores were identified in a larger proportion of
      managers, clerks, and in persons with university education than in manual workers
      and persons with only primary and secondary education. There was no difference
      between smokers and non-smokers and religious and nonreligious scorers. There was
      no difference in ratings for life needs satisfaction between persons identified
      as having scores on Type A and Type B behavior. The present analyses enhance our
      understanding of Type A behavior as related to age, sex, occupation, education,
      and life needs satisfaction in a Croatian sample.

PMID- 7501752
TI  - Influence of the alpha 2 noradrenergic antagonist piperoxane on longevity in the
      Fischer-344 rat: a preliminary report.
AB  - Piperoxane is an alpha 2-noradrenergic antagonist with demonstrated excitatory
      effects on neurons in the locus coeruleus, causing a corresponding increase in
      norepinephrine in many forebrain areas. 16 male Fischer-344 rats approximately 16
      months of age were injected with 3 mg/kg of piperoxane or .09% saline. The
      piperoxane-treated rats lived an average of 127.1 days longer than the saline
      treated rats. The results are discussed in terms of the effects of strategies
      designed to enhance brain levels of catecholamine and their effect on the aging
      process. A discussion of further research is also presented.

PMID- 7501753
TI  - Optimistic bias in cancer risk perception: a cross-national study.
AB  - Results are presented from a pilot study in which risk perceptions for developing
      cancer in samples of American and British adults were compared. 61 American and
      43 British people estimated the likelihood of cancer happening to themselves and
      the average person. As a group, participants tended to judge their personal
      likelihood of developing cancer as less than the average, supporting the presence
      of an optimistic bias. However, compared to the Americans, British respondents
      tended to perceive both themselves and the average person to be less likely to
      develop cancer. There were no gender differences or interactions between the
      variables. Discussion centered on possible variations between the two countries
      with respect to perceptions of control and responsibility for one's health status
      which may account for the findings.

PMID- 7501754
TI  - Cognitive determinants of quality of life after onset of cancer.
AB  - To investigate cognitive coping styles and how they might relate to perceived
      quality of life for individuals seriously ill with cancer 41 mostly elderly, male
      patients with a wide variety of cancers were administered the Illness Effects
      Questionnaire, a quality of life measure, the COPE Questionnaire, which samples
      different coping strategies, and questions regarding beliefs about illness
      behaviors, expectations about cancer's effects, comparisons of the participants'
      lives with those of others, feelings since having cancer, and motivation to
      resist lifestyle disruptions. Six of the belief factors and two of the coping
      strategies were related to perceived quality of life. If the effects of cancer
      were less than expected, quality of life was better; with an expectation of a
      negative effect from the disease, lowered quality of life was perceived. Two
      coping strategies were related to quality of life, suppression of competing
      activities and using religious practices. Other relationships were also
      discussed.

PMID- 7501755
TI  - Power of a test that is robust against variance heterogeneity.
AB  - Welch (1947) proposed an adjusted t test that can be used to correct the serious
      bias in Type I error protection that is otherwise present when both sample sizes
      and variances are unequal. The implications of the Welch adjustment for power of
      tests for the difference between two treatments across k levels of a concomitant
      factor are evaluated in this article for k x 2 designs with unequal sample sizes
      and unequal variances. Analyses confirm that, although Type I error is uniformly
      controlled, power of the Welch test of significance for the main effect of
      treatments remains rather seriously dependent on direction of the correlation
      between unequal variances and unequal sample sizes. Nevertheless, considering the
      fact that analysis of variance is not an acceptable option in such cases, the
      Welch t test appears to have an important role to play in the analysis of
      experimental data.

PMID- 7501756
TI  - Time pressure, type A syndrome, and organizational citizenship behavior: a field
      study replication of Hui, Organ, and Crooker (1994)
AB  - A field study of 182 university students in their residences tested the
      relationships among subjective time pressure, Type A scores, and organizational
      citizenship behavior. Perceived time pressure did not inhibit any form of
      citizenship behavior. Scores on the Achievement-Striving dimension of the Type A
      measure were positively related to the impersonal form of citizenship behavior as
      well as perceived time pressure and grade point average.

PMID- 7501757
TI  - Depression and suicidal ideation in African American and Caucasian students.

PMID- 7501758
TI  - Job satisfaction of special education teachers.

PMID- 7501759
TI  - 16 PF profiles and typologies for patients seen in marital therapy.
AB  - The purpose of this study was to examine and describe the personality
      characteristics of 145 patients seen in outpatient marital therapy in private
      practice. Cluster analysis of the entire sample resulted in five separate
      typologies which were statistically significant and clinically meaningful and
      which suggested different goals for counseling. Patients seeking marital therapy
      were significantly more tense, anxious, worrisome, suspicious, bold, and shrewd
      than the normal persons in the 16 PF standardization sample.

PMID- 7501760
TI  - Health practices and mental health revisited.
AB  - The relationships of seven health practices with a measure of mental well-being
      were explored in a sample of 490 university students. Mental well-being was
      associated with moderate exercise and regular sleep.

PMID- 7501761
TI  - Differential diagnostics and treatment of an inpatient adolescent showing
      pervasive developmental disorder and mania.
AB  - A study of a 16.8-yr.-old female is presented to highlight aspects of Asperger's
      Syndrome as distinguished from cognate developmental and mood disorders. Brief
      therapy and pharmacological implications are mentioned.

PMID- 7501762
TI  - Humor preferences among angered males and females: associations with humor
      content and sexual desire.
AB  - Previous research has indicated a connection between the appreciation of
      different content types of humor and the effectiveness of laughter to reduce a
      hostile mood. Although a person's state of arousal can influence the preferences
      shown for a particular type of humor, little research has examined how sexual
      desire may contribute to preferences for humor. Anger was experimentally induced
      in 180 men and 180 women who had noted sexual desire before exposure to humor
      with sexual, sexist, and neutral content. Assessment of appreciation scores
      showed that angered men and women preferred sexual and sexist humor when they
      reported high sexual desire. Mood assessment indicated this appreciation related
      to the removal of anger and the reporting of a happy state with low ratings of
      sexual desire. Participants preferred neutral humor and showed least appreciation
      of sexist humor. Also, they did not enjoy a reduction in their hostile mood
      following exposure to humor.

PMID- 7501763
TI  - Children's drawings and attachment to pets.
AB  - To help confirm the concept that distances placed between the self and other
      figures in children's drawings represent emotional distances, 242 pet-owning and
      35 nonpet-owning kindergartners through eighth graders drew pictures of
      themselves, a pet, and/or a family member. Owners drew pets significantly closer
      than family-figures although the younger the child, the greater the distance
      between self and pet. Older children drew themselves holding pets significantly
      more often, but younger children placed the family-figure between the self and
      the pet significantly more often. There were no significant gender differences in
      self-figure/pet-figure distances, but cats, dogs, caged animals, and farm animals
      were placed significantly closer to self-figures than were fish. Over-all, owners
      were clearly emotionally closer to pets than to family members, but nonowners
      were as close emotionally to family members as were owners.

PMID- 7501765
TI  - Sociocultural differences on hostility in alexithymic persons.
AB  - A recent comment by I. Alex Rubino on the personality correlates of alexithymia
      implied that there are several important areas for further discussion.
      Sociocultural differences in ethnicity (Japanese and Italian) may need to be
      taken into account for an understanding of the divergent findings.

PMID- 7501764
TI  - Executive functions of the frontal lobes: psychometric properties of a self
      rating scale.
AB  - This study investigated the psychometric properties of a self-rating scale
      designed to test the executive functions of the frontal lobes. A set of 16 items
      was selected, based on face validity, from the 200-item Coolidge Axis II
      Inventory. Cronbach scale reliability for the new scale was .72 on 1,223
      purportedly normal participants. A factor analysis yielded a three-factor
      structure, Decision-making difficulties (8 items, 23% of the variance, scale
      reliability .77), Poor planning (4 items, 15% of the variance, scale reliability
      .63), and Task incompletion (6 items, 9% of the variance, scale reliability .66).
      A multivariate analysis of variance, performed on the overall scale sum and the
      three subscales, between 17 closed head-injured patients and a matched control
      group was significant. The head-injured patients scored significantly higher on
      the over-all measure of executive dysfunction and higher on the decision-making
      difficulties subscale but not on the other two subscales.

PMID- 7501766
TI  - Associations of neuroticism and introversion with academic achievement.
AB  - The relationship of academic achievement or grades with Eysenck Personality
      Inventory scores on Neuroticism and Introversion was examined. Contrary to
      theoretical expectations and previous studies, no significant differences among
      means were observed for 118 first-year South African university students (78
      women and 40 men) whose mean ages were 29 yr. (women) and 28.8 yr. (men).

PMID- 7501767
TI  - A behavioral nosology for tinnitus.
AB  - Studies of the physiological and psychological characteristics of tinnitus and
      its treatment have yielded a variety of conclusions. The variation in results may
      reflect heterogeneous patient populations. Although the sources of variation are
      many, one may be derived from combining patients of several severities of
      tinnitus into a single group. A nosology is proposed for tinnitus severity to be
      classified by the patient's behavioral responses. Classifying patients allows
      direction to specific treatment modalities and will facilitate research. The
      concept of phantom auditory pain and a rational basis for the use of
      antidepressant therapy are discussed.

PMID- 7501768
TI  - The structure of psychological distress.
AB  - In this study we describe the factor structure of the Psychological Distress
      Index used in the Quebec Health Survey and compare a model that includes
      psychophysiologic symptoms (29 items) with a model restricted to cognitive and
      affective symptoms only (18 items). Three samples (n = 2,000) were used to test
      the likelihood of these two models. Confirmatory factor analyses were carried out
      using LISREL VII. Logistic regression was then used to examine the association of
      the two versions with demographic variables and health indicators. Analysis
      indicates that both versions show satisfactory construct validity. Except for
      age, the associations observed between both versions and respondents' demographic
      characteristics are similar; however, the 29-item version is more strongly
      associated with health status indexes, suggesting a possible bias attributable to
      somatic items.

PMID- 7501769
TI  - Effects of the detoxification of domestic gas on suicide rates in six nations.

PMID- 7501770
TI  - Adaptation to homelessness: self-actualization, loneliness, and depression in
      street homeless men.
AB  - Adaptation to homelessness was investigated in a sample of 145 street homeless
      men using loneliness and depression scales and the construct of self
      actualization. Principal components analysis with varimax rotation of a matrix of
      correlations of measures on the history of being homeless, demographic data,
      scores on loneliness and depression scales, and self-actualization measures gave
      a 3-factor model of adjustment: adaptive striving, detachment, and adaptive
      resources. Maslow's and Sullivan's contention that satisfying interpersonal
      relationships are common pathways to mental health was affirmed.

PMID- 7501771
TI  - Prednisolone blocks extreme intermale social aggression in seizure-induced, brain
      damaged rats: implications for the amygdaloid central nucleus, corticotrophin
      releasing factor, and electrical seizures.
AB  - In two separate blocks of experiments, the extreme within-group aggression which
      is typically associated with limbic seizure-induced brain injury in male rats was
      attenuated or abolished within two days by the administration of prednisolone in
      the water supply. The effect was specific to the aggression and was not simulated
      by dexamethasone. The results support the hypothesis that interference with
      inhibitory inputs to the central nucleus of the amygdala and the enhanced
      stimulation by corticotrophin-releasing factor facilitates physical aggression
      within groups of male rats. Potential relevance to curbing aggression
      ("conflict") between groups of male humans is discussed.

PMID- 7501773
TI  - Myths about childhood suicide.

PMID- 7501772
TI  - Childhood antecedents of stable positive symptoms in schizophrenia.
AB  - For a longitudinal study of 29 males with an initial diagnosis of schizophrenia
      as young adults, childhood information identified excitable behavior as most
      strongly related to subsequent positive symptoms. This childhood variable was
      related to stable but not to unstable positive symptom measures. Further, stable
      positive symptoms were limited to the subgroup with a history of excitable
      behavior.

PMID- 7501774
TI  - Set-shifting aptitude in Parkinson's disease: external versus internal cues.
AB  - A modified version of the odd-man-out test was used to investigate set-shifting
      aptitude in 12 patients with Parkinson's disease. We asked subjects to execute in
      alternation two different sorting rules over successive items. External and
      internal cueing conditions were employed. Patients with Parkinson's disease were
      impaired on the tasks with internal cues but were normal on the tasks with
      external cues. Moreover, the shift costs were consistently larger for the shift
      to the easier task than the shift to the more difficult task. These findings
      indicated that the model of 'Supervisory Attentional System' may not be
      sufficient to explain the data as Brown and Marsden (1988) originally suggested.

PMID- 7501775
TI  - The imposter phenomenon in teachers and accountants.

PMID- 7501776
TI  - Domestic terror and rates of suicide and homicide in Canada, 1960-1985.

PMID- 7501777
TI  - Some interpersonal and attitudinal factors characterizing patients satisfied with
      medical care.
AB  - This research investigated the extent to which interpersonal and attitudinal
      factors affect the doctor-patient relationship. A questionnaire survey of people
      living in northeastern Kansas who had experience with medical care was conducted.
      Dependent measures were over-all patient satisfaction, patient's attitude toward
      death of self or others, causality orientation, attitude toward health and
      disease, and perception of the doctor-patient relationship. The majority of test
      subjects (92%) reported satisfaction with their medical care. A significant
      correlation between fear of death of significant others and scores on causality
      scales reflects feelings of not being in control of one's life. Other
      associations indicate that people who do not feel in control of their lives
      depend on traditional and folk remedies. Scores showing low fear of own death
      correlated significantly with the rated greater sense of responsibility for own
      health and treatment. Patients who rated themselves as more needy were
      unsatisfied with their care and those whose doctors called them by first name
      tended to be more content. Even in populations satisfied with their medical care,
      we suggest that the quality of care could be improved by attention to
      interpersonal and attitudinal factors.

PMID- 7501778
TI  - Composite probability modelling of increasing resolution where diagnostic
      covariates are unmeasurable for some subjects.
AB  - When predictive covariates for a dichotomous outcome dependent variable are
      undetectable or unmeasurable for some subjects, a fact in itself that may be of
      considerable prognostic importance, traditionally such subjects' data are dropped
      from multiple logistic regression analyses. An alternative analytical algorithm
      is offered here for such situations. First, a series of multiple logistic
      regressions are applied to the complete data where covariates are initially coded
      as dichotomous, e.g., detectable or nondetectable. Then, a second series of
      logistic regressions are fitted for those subjects for whom a covariate is
      detectable and measurable with the fully resolved measure as the covariate.
      Ultimately, all individual model-specific predicted probabilities of the outcome
      for a subject are combined into a single probability through the proposed
      "Composite Probability Modelling of Increased Resolution" (CPMIR). When such an
      analysis was applied to discriminate 133 patients with acoustic tumours from a
      sample of 133 patients with cochlear disease, using a latency measure of the
      auditory brainstem response evoked potential as the predictive covariate, CPMIR
      yielded a superior model chi square to any component model, used the full cohort
      of patients, and produced the largest area under the ROC curve. This algorithm is
      offered as a general statistical modelling device.

PMID- 7501779
TI  - Gender influence on perceptions of hostile environment sexual harassment.
AB  - Perceptions of sexual harassment were investigated as a function of perpetrators'
      and recipients' gender. Undergraduate students (100 women, 98 men) were presented
      34 scenarios of men and women interacting at work. Participants were asked to
      read carefully each scenario and indicate on a scale anchored by 1 (strongly
      disagree) and 7 (strongly agree) their opinions as to whether the scenario
      represented an incident of sexual harassment. Analysis indicated that women rated
      "hostile environment" scenarios as more harassing than men, and male perpetrators
      were rated as more harassing than female perpetrators. Even though some scenarios
      were rated as more harassing than others, the full range of the 7-point scale was
      used on every scenario, indicating a lack of agreement on what constitutes
      harassment. This lack of agreement highlights the debate within the legal
      community about whether the "reasonable person" or the "reasonable woman"
      standard should be used to judge sexual harassment in the workplace.

PMID- 7501780
TI  - Elements of critical incident debriefing.
AB  - The present paper lists a number of specific therapeutic steps involved in
      critical incident debriefing. These therapeutic suggestions, while by no means
      exhaustive, include (a) identification, (b) labeling, (c) articulation, (d)
      expression, (e) externalization, (f) ventilation, (g) validation, and (h)
      acceptance. More careful attention to these specific elements--regardless of
      debriefers' training and backgrounds--might improve therapeutic consistency for
      trauma victims afflicted with stress-related symptoms. Further applications of
      these therapeutic steps were also suggested for other types of behavioral
      problems.

PMID- 7501781
TI  - Clinical guidelines. Now or never.

PMID- 7501782
TI  - Multifetal pregnancy reduction. A review of an evolving technology and its
      psychosocial implications.
AB  - Multifetal pregnancy reduction is the elective termination of gestation of a
      preselected number of fetuses in a multiple pregnancy to improve perinatal
      outcome. As improved techniques of infertility treatment are yielding more high
      order multiple gestations, multifetal pregnancy reduction is being performed more
      frequently. The authors review the abundant literature on technique, the moderate
      amount of literature on ethics, and the minimal literature on the psychological
      consequences of this procedure, and describe the experience of the patients and
      their partners. The complexities of studying this area are discussed. Besides
      management of psychiatric complications, liaison psychiatrists could play an
      active role in structuring multifetal pregnancy reduction programs to optimize
      counseling and the patients' experience.

PMID- 7501783
TI  - Psychiatric diagnoses and sexual victimization in women with chronic pelvic pain.
AB  - The authors evaluated 100 women scheduled for diagnostic laparoscopy (50 for
      chronic pain, 50 for tubal ligation or infertility evaluation) using structured
      psychiatric, family history, and sexual trauma interviews. Laparoscopy reports
      were blindly rated by a gynecologist. Compared with the nonpain group, the women
      with chronic pelvic pain had significantly higher current and lifetime rates of
      psychiatric disorders, as well as childhood and adult sexual victimization. They
      reported significantly higher mean numbers of somatization symptoms, but no
      significant differences in objective laparoscopic findings. Psychiatric disorders
      and sexual victimization are common in women with chronic pelvic pain and should
      be considered in the evaluation and treatment of these patients.

PMID- 7501784
TI  - The association between intravenous haloperidol and Torsades de Pointes. Three
      cases and a literature review.
AB  - Torsades de Pointes (TDP) is a potentially malignant ventricular arrhythmia that
      often has a drug-induced origin. Oral, but not intravenous, haloperidol has been
      generally associated with this arrhythmia. The authors detail three patient cases
      of TDP that occurred while the patients were receiving intravenous haloperidol.
      The authors discuss the known risk factors for the development of TDP and review
      the literature on ventricular arrhythmias associated with haloperidol use.

PMID- 7501785
TI  - Psychiatric symptoms in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is an unusual neurodegenerative disorder
      that superficially resembles Parkinson's disease (PD). It is characterized by
      gaze palsy, bulbar signs, parkinsonian signs, and mental changes. While mental
      changes are a frequent finding, they have, with the exception of dementia, been
      poorly defined. In this study, 19 patients with PSP were evaluated
      psychiatrically and compared with 42 patients with PD. Fifty-two percent of the
      patients had some degree of dementia, as measured by the Mini-Mental State Exam.
      Eight (42%) of the PSP patients had other psychiatric diagnoses, mostly
      relatively mild depression or anxiety, though two patients had more severe
      depression. Six (32%) patients had pathologic laughing or crying, and four of
      these had a psychiatric diagnosis other than dementia. The PSP patients did not
      differ from the PD patients on measures of depression or anxiety and did not have
      a greater rate of formal psychiatric diagnoses. This study confirms previous
      reports of dementia as a common feature of PSP. It further suggests that
      psychiatric disturbances, while common, are generally relatively mild, though
      more serious psychiatric illness may be seen.

PMID- 7501786
TI  - Physical fitness and perceived stress. Relationships with coronary artery disease
      risk factors.
AB  - This study evaluated the relationship between two biochemical risk factors for
      coronary artery disease, serum lipids and dehydroepiandrosterone-sulfate (DHEA
      S), and both fitness and perceived stress among a cohort of senior male Army
      officers (N = 331). The participants underwent a number of assessments gauging
      their fitness [exercise tolerance as measured by maximum ventilatory oxygen
      uptake (MVO2)], psychological well-being, and biochemical cardiovascular risk
      factors. Perceived stress was significantly and inversely related to DHEA-S
      levels, even after adjusting for age, though no relationship was found between
      perceived stress and serum lipids. Significant correlations were found between
      MVO2 and high-density lipoprotein cholesterol and inversely between MVO2 and
      triglycerides. Overall, the study's findings are generally consistent with the
      view that psychological stress and physical activity have opposite effects on
      parameters that affect cardiovascular status.

PMID- 7501788
TI  - Self-esteem and depressive symptomatology in children with somatoform disorders.
AB  - This study investigated levels of self-esteem and self-reported depressive
      symptomatology in a sample of children diagnosed with somatoform disorder. The
      somatoform sample, a sample of children with depressive disorders, and a sample
      of children with no DSM-III-R diagnosis differed significantly on measures of
      depression and self-esteem. Specifically, the somatoform group consistently
      scored between the depressed and no-diagnosis groups, although most of the
      statistically significant differences occurred between the depressed and no
      diagnosis groups. Significant differences between the somatoform group and the
      other groups were found for behavioral self-esteem.

PMID- 7501789
TI  - Globus pharyngis, personality, and psychological distress in the general
      population.
AB  - The authors approached 1,158 middle-aged women, who were assessed for the
      presence of the globus sensation in the prior 3 months. Seventy globus "cases"
      (6.0%) were identified. Twenty-eight women with globus and 35 control subjects
      completed a series of questionnaires designed to assess personality traits and
      psychological distress. The globus subjects were significantly higher on
      neuroticism and low on extra-version and had significantly elevated levels of
      psychological distress, including anxiety, low mood, and somatic concern when
      compared with the control subjects. Severity of throat symptoms, but not
      personality or psychological distress scores, predicted the degree of medical
      help sought for the symptom.

PMID- 7501787
TI  - Psychiatric disease and cytomegalovirus viremia in renal transplant recipients.
AB  - Although cytomegalovirus (CMV) is rarely cultured from peripheral-blood
      leukocytes of immunocompetent patients, it may be cultured from up to 60% of
      renal transplant recipients, 1 to 4 months after transplantation. During this
      same period, renal transplant recipients are often referred for psychiatric
      evaluation. Since CMV may infect the central nervous system, the relationship
      between isolation of CMV from peripheral-blood leukocytes (viremia) and
      psychiatric evaluation was investigated in 80 renal allograft recipients at the
      Massachusetts General Hospital. Five of 16 (31%) patients with viremia and 7 of
      64 (11%) patients without viremia required psychiatric consultation (P = 0.04,
      two-tailed Fisher exact test). CMV viremia may be an important but treatable
      contributor to psychiatric symptoms in the transplant recipient.

PMID- 7501790
TI  - Risperidone and the treatment of delusions of parasitosis in an elderly patient.

PMID- 7501791
TI  - Sertraline with methylphenidate in an ICU patient.

PMID- 7501792
TI  - Successful treatment of comorbid panic disorder and sleep apnea with continuous
      positive airway pressure.

PMID- 7501793
TI  - [Anatomy and pathophysiology of deglutition disorders].
AB  - In the nervous system there are many automatized functions that require
      multilevel control. Some of them are more important because of their link with
      some vital functions. Only two are crucial to survival: respiration and the
      pumping of the heart. Swallowing is integrated within the respiratory system,
      explaining the need for great reliability and justifying the complexity of the
      organization described. The progress of medical imaging techniques has created
      new conditions for practicing radiologists, who need to know much more anatomy
      than in the past. Therefore, it is easier to learn anatomical details if there
      details are understood as part of an intelligent construction. We hope to have
      been able to demonstrate that swallowing is one good example of the real
      competency of the constructor of this system.

PMID- 7501794
TI  - [The pharyngoesophageal segment].
AB  - The pharyngoesophageal segment (PES) is a striated muscular structure separating
      the relatively wide pharynx from the narrow cervical esophagus. There is a
      substantial axial and longitudinal asymmetry within the PES, as well as basal
      resting pressure that is substantially influenced by a variety of stimuli as well
      as deglutition.

PMID- 7501795
TI  - [Functional disorders of the esophagus. Radiologic diagnosis].
AB  - Radiological evaluation of esophageal motility and the lower esophageal sphincter
      has gained increased attention in recent years. Videofluoroscopic investigation
      of esophageal motor function is superior to static film radiography, as repeated
      analysis of the videotaped recordings is possible. With emphasis on radiological
      techniques, normal esophageal physiology and motility and a variety of esophageal
      motor disorders are discussed in this review paper. Radiological evaluation of
      gastroesophageal reflux and reflux esophagitis is described. Clinical and
      radiological findings in esophageal motility disorders and gastroesophageal
      reflux disease and the radiological efficacy compared to that of manometry and pH
      metry are discussed.

PMID- 7501796
TI  - [Videocinematography of swallowing. Indications, methodology and findings].
AB  - The purpose of this study was to given an introduction to the radiological
      evaluation of deglutition. The symptoms leading to videofluoroscopic
      investigation of swallowing are explained. The examination has to be tailored to
      the patient's symptoms. Each film scene depicts a characteristic patient
      position, a particular kind of contrast material and a certain amount. A
      systematic approach to analyze video films of deglutition and knowledge of the
      normal and abnormal swallowing functions are mandatory.

PMID- 7501797
TI  - [Videocinematography and pre- and postoperative diagnosis of lip-maxillary
      palatal clefts].
AB  - Videocinematography is a valuable tool in the diagnostic workup and planning of
      functional surgery in cleft patients. The high resolution and depiction of the
      finest mucosal structures in motion allow objective and dynamic assessment of the
      individual velopharyngeal function. A total of 170 cleft patients were examined
      by videocinematography, and the results were compared to nasoendoscopy and to the
      clinical examination. The marked superiority of this radiological technique with
      regard to clearness of depiction and ease of use is shown. It can therefore be
      recommended without reservation for the pre- and postoperative assessment of
      cleft patients.

PMID- 7501798
TI  - [Efficacy of high-frequency cinematography in diagnosis of dysphagia].
AB  - Dysphagia is a common symptom in clinical practice. Due to the broad spectrum of
      underlying diseases many disciplines are involved in the therapy and diagnosis of
      dysphagia, where radiology plays a central role. The radiologist is confronted
      with different diagnostic problems and has to choose the most appropriate type of
      investigation. In many cases no organic disorder can be demonstrated by clinical
      examination, endoscopy or conventional radiological techniques. In this setting
      cineradiography is an outstanding tool for finding functional or structural
      changes in the swallowing chain. This study underlines the efficiency of
      cineradiography in the diagnosis of dysphagia.

PMID- 7501799
TI  - [Radiologic assessment of globus pharyngis. Comparison of the diagnostic value of
      conventional roentgen with videocinematography].
AB  - The feeling of having a lump in the throat is a common complaint of ENT
      outpatients. The symptom is associated with a multitude of pharyngoesophageal
      abnormalities. Our study compares the diagnostic yield of videofluoroscopy to
      that of static radiography in patients suffering from globus pharnygis. A total
      of 150 consecutive patients complaining of a lump in the throat, but without
      evidence of dysphagia, were studied in a standardized fashion with both methods.
      Videofluoroscopy combined with static radiography revealed morphological or
      functional abnormalities in 75% of our patients. The combination of the two
      methods yielded significantly more abnormalities in the pharynx and esophagus
      than videofluoroscopy (P < 0.0001) or static radiography alone (P < 0.0001).
      Esophageal motor disorders, pharyngoesophageal sphincter dysfunction and
      pharyngeal residue of contrast material proved to be the most common
      abnormalities. In conclusion, videofluoroscopy combined with static radiography
      is mandatory in the radiological assessment of patients suffering from the globus
      sensation.

PMID- 7501800
TI  - [Radiologic differential diagnosis of neurologically-induced deglutition
      disorders].
AB  - This paper explains the differential diagnosis of neurological dysphagia. Special
      groups of diseases are described that can only be assessed by dynamic recording
      modalities like videofluoroscopy and high-speed cineradiography. The need for
      dynamic recording results from the physiological data of deglutition. The act of
      deglutition lasts only 0.7 s, but requires the well-coordinated action of 5
      cranial nerves and 26 muscle groups. For a systematic analysis of the underlying
      neurological disease a precise description of possible pathological single
      observations from the oral cavity to the cardia is offered to the radiologist.
      Important hints concerning possible "pitfalls" due to non-neurologically caused
      pharyngoesophageal motility disturbances are given. Although dynamic recording
      does not always allow the precise diagnosis of the underlying neurological
      disease, it enables us to classify the motor disturbances and leads to distinct
      "groups of disease." Thus, dynamic recording of deglutition is of crucial
      importance for further conservative or functional surgical treatment of the
      dysphagic patient.

PMID- 7501801
TI  - [Analysis and radiologic staging of the type and severity of aspiration].
AB  - The estimated number of the incidence of undiagnosed chronic aspiration pneumonia
      after cerebral or cerebrovascular injury seems very high. According to American
      statistics, at least 6% of these patients die from aspiration pneumonia within
      the first year. The high temporal resolution of cineradiography with frame rates
      of the complex process of pharyngeal swallowing lasting 0.7 s. The method enables
      us to differentiate between so-called pre-, intra- and postdeglutitive
      aspiration, which means aspiration before, during and after the triggering of the
      swallowing reflex. Together with an established score for the severeness of the
      aspiration, the method supplies important data for setting up a functional
      surgical and/or conservative program for rehabilitation and for follow-up
      studies.

PMID- 7501802
TI  - [Classification and interpretation of the oral swallowing phase using B+M mode
      ultrasound].
AB  - A cushion device and B+M mode ultrasonography technique were used in 30 healthy
      volunteers to study tongue movement during swallowing. M-mode images show an
      amplitude-time diagram, in which the entire tongue movement during swallowing can
      be easily scrutinized. The different tongue movements during swallowing result in
      several turning points on the graph of the M-mode sonogram, which divide the oral
      swallowing phase into five subphases (I, IIa, IIb, IIIa, IIIb). Based on this new
      classification of swallowing, the tongue movements of the participants were
      interpreted and classified.

PMID- 7501803
TI  - [Simultaneous video radiography and "solid state" intraluminal pharyngeal
      manometry during barium swallow; video manometry].
AB  - Recent advances in technology, including computerized analysis, have renewed
      interest in pharyngeal manometry. Simultaneous fluoroscopy and videography have
      been recommended by many authors. This article reviews the history of pharyngeal
      manometry and highlights some of the technical difficulties involved. We also
      report the current status of the simultaneous technique and summarize our own
      results as well as those reported by other research groups.

PMID- 7501804
TI  - [Color-coded duplex ultrasound in chronic dissecting abdominal aortic aneurysm.
      Differentiation between true and false aortic lumen with reference to the blood
      supply to larger abdominal arteries].
AB  - PURPOSE: This study was carried out to evaluate the ability of color-coded duplex
      sonography (CCDS) to differentiate between true and false aortic lumen with
      regard to the blood supply to the major aortic branches in cases of chronic
      dissecting abdominal aortic aneurysm. METHODS: In eight patients with aortic
      dissection, the Doppler spectrum was analyzed for maximum systolic velocity
      (Vmax), pulsatility index (PI), acceleration time (AT), acceleration index (HAN
      DA index, AI), and, in renal arteries, for the side ratio of AT and AI (AT-R, AI
      R). Computerized tomography and angiography were used to define blood supply to
      the aortic branches by true and false aortic lumen. RESULTS: Four of five iliac
      arteries with continued dissection showed differences between true and false
      lumen in all Doppler parameters; one showed no difference. In the remaining iliac
      arteries and the viseral branches, blood supply by true or false aortic lumen
      could not be differentiated by CCDS. CONCLUSION: In cases of chronic dissecting
      abdominal aortic aneurysm, CCDS is not able to differentiate between true and
      false aortic lumen with regard to the blood supply to the major aortic branches.

PMID- 7501805
TI  - [Recurrent benign esophageal stenosis?].

PMID- 7501806
TI  - [3-D imaging of the liver].
AB  - Three dimensional imaging of the liver is focused on the spatial visualization of
      focal lesions in relation to vascular landmarks to support surgical decision
      making. Additionally the volume estimation of metastases or liver segments is
      considered in the patient's oncologic follow-up and the planning of the surgical
      approach. Spiral-CT is destined for 3D imaging, as it represents a standardized,
      minor invasive, time and cost saving method. Current developments of 3D
      sonography of the liver are reported. While a special application of 3D imaging,
      i.e. CT angiography (CTA), replaces preoperative arterial angiography in liver
      transplantation candidates the diagnostic gold standard for lesion detection
      still remains by reason of missing algorithms the interpretation of a 2D data
      set. Validation of 3D versus 2D imaging of the liver demands controlled trials to
      evaluate the diagnostic potential, time and cost savings of dedicated acquisition
      techniques, postprocessing algorithms and display modalities.

PMID- 7501807
TI  - Non-metastatic childhood ependymomas.
AB  - PURPOSE: Intracranial ependymomas of childhood are relatively infrequent. There
      are significant disagreements concerning optimal postoperative treatment as well
      as the patterns of relapse following treatment. The purpose of this retrospective
      study was the analysis of the recurrence pattern and therefore the implication on
      the extent of the radiotherapy fields. Data from 37 patients referred within 19
      years were used for this study. PATIENTS AND METHODS: From April 1975 to July
      1993, 37 children aged 1-14 years were referred for postoperative treatment of an
      intracranial ependymoma. Twenty-eight children received postoperative radiation
      therapy and 26 patients received chemotherapy. The median follow-up is 6 years
      (range 2 months to 19 years). RESULTS: Overall survival and event free survival
      at 5 and 10 years were 40%. Eighteen children relapsed. Relapses occurred from
      1.5 months to 3.6 years post treatment. Relapses were distant in four cases and
      local in 14. Age, sex, extent of primary resection, chemotherapy and type of
      radiation therapy did not influence the outcome. Children with poorly
      differentiated tumors who did not receive postoperative radiation therapy had a
      higher relapse rate but this difference is not statistically significant.
      CONCLUSIONS: Despite doses of radiation > or = 50 Gy the majority of recurrences
      were local. Our results, despite the small number of patients are in accordance
      to those previously published, suggest that prophylactic craniospinal irradiation
      is superfluous. Better means of achieved local control are required, such as
      three-dimensional conformal radiation therapy with dose-escalation study or
      hyperfractionation regimen.

PMID- 7501808
TI  - Factors influencing the degree of erythematous skin reactions in humans.
AB  - Dose-response relationships have been studied using an ordinal visual scale and
      reflectance spectrophotometry data from 123 treatment sites on 110 patients
      treated with 10 dose fractions over 12-14 days. Dose rates varied between 3 and
      240 Gy/h and total doses of between 25 and 41 Gy were given using teletherapy
      apparatus. We found qualitative scoring of erythematous skin reactions to be
      subject to considerable inter- and intra-observer variation. Reflectance
      spectrophotometry provided more reproducible information, some of which was
      undetectable by naked eye. Baseline erythema readings were significantly higher
      in male patients and at anatomical sites of previous heavy UV exposure. In
      addition, a pronounced decline in erythema readings during the second week of
      therapy and 'reciprocal vicinity' (abscopal) effects adjacent to the field,
      undetected by the eye, were observed in a subset of patients. Meaningful dose
      response relationships could be derived only from reflectance data with peak
      change from the pretreatment baseline measure providing the best discrimination.
      Peak erythema measures following treatment were found to depend on the age and
      gender of the patient as well as the treatment site and its baseline erythema
      measurement. This was independent of the total dose administered or the
      instantaneous dose rate at which it was delivered. The rate of erythema
      development was also dose rate dependent but only weakly dependent on the
      biological dose intensity (Gy equiv./day) of the treatment course. The data raise
      the question of whether irradiation-induced erythema is exclusively a secondary
      phenomenon occurring as a result of basal cell killing. The short repair half
      time value of 0.06 h obtained by direct analysis is perplexing and may reflect a
      dose rate-dependent physiological vasodilatory response to irradiation and/or a
      multi-component cellular repair process.

PMID- 7501809
TI  - Impact of changes in the treatment of nasopharyngeal carcinoma: an experience of
      30 years.
AB  - Two hundred and twenty-eight patients with nasopharyngeal carcinoma were treated
      in a single institution in a 31-year period. Overall survival (OS), disease-free
      survival (DFS), and complete response (CR) rates were analyzed. In addition,
      survival and control rates from 1960 to 1975 and from 1976 to 1991 were
      evaluated. In the latter group, a comparative study was performed between
      patients treated with neoadjuvant chemotherapy (NCT) before radiotherapy (RT)
      (45) and patients treated with radiotherapy alone (45). OS at 5 and 10 years were
      42 and 34%, and DFS rates were 35 and 30%, respectively. CR was achieved in 184
      patients (81%). Tumor progression and survival were strongly associated with T
      category. Use of fashioned blocks, age and T-category were the most important
      factors influencing survival in a multivariate analysis. In the patients treated
      with NCT, rates of CR and OS were not significantly different when compared with
      the concurrent RT alone group. Ninety-nine patients had recurrence (54%) and 58
      received rescue treatment. Modern radiotherapy techniques have greatly assisted
      in the improvement of tumor control rates. Chemotherapy must be further evaluated
      and new treatments for relapsed patients are needed.

PMID- 7501810
TI  - Changes in S-phase fraction and micronucleus frequency as prognostic factors in
      radiotherapy of cervical carcinoma.
AB  - Twenty-five patients with cervical carcinoma were treated with combined external
      beam and high dose rate afterloading radiotherapy. Biopsies obtained at different
      time points in the course of therapy were analysed with respect to cell
      proliferation and cytogenetic damage. The fraction of cells with an S-phase DNA
      content as well as the frequency of micronuclei were determined. These two
      parameters were then related to treatment outcome, in particular patient
      survival. Neither S-phase fraction nor the micronucleus frequency before
      radiotherapy were predictive of treatment outcome in this small group of
      patients. However, when changes in response to therapy were considered, patients
      whose S-phase fraction decreased and patients whose micronucleus frequency
      increased tended to have a better prognosis. Although statistical significance
      was not achieved with either criterion alone, when applied together the
      combination predicted patient survival quite reliably; the 5-year survival rate
      of those patients who showed a decrease in S-phase fraction as well as an
      increase in micronucleus frequency was about 90% in contrast to less than 30% for
      the non-responders (p < 0.03).

PMID- 7501811
TI  - Irregular variations in radiation sensitivity when the linear energy transfer is
      increased.
AB  - Seven cell lines were analyzed for clonogenic survival after irradiation with
      photons (60Co) or accelerated helium or nitrogen ions. The cell lines showed
      different sensitivity to photon radiation and most of the differences decreased
      after irradiation with helium ions with a linear energy transfer (LET) of about
      40 keV/microns. However, all cell types had individual LET sensitization patterns
      and the mean relative biological effectiveness (RBE) at 10% survival ranged from
      1.46 +/- 0.12 to 2.41 +/- 0.26 for the helium ions. This difference was
      significant and the differences increased further when higher survival levels
      were considered. There was only a weak tendency towards a relation between photon
      and helium ion sensitivity when the linear component of the survival curves, the
      alpha-values, were compared, and no relation at all for other parameters. It was
      not possible to predict the response to an increased LET from the photon
      responses obtained. Three of the cell lines were also irradiated with nitrogen
      ions with an LET of 125 keV/microns. These cells were, as expected, sensitized
      further and the average RBE at 10% survival was 3.67 +/- 0.67. However, one cell
      line was more resistant than the others in this case. Furthermore, the quadratic
      component of the survival curves, the beta values, were higher after irradiation
      with nitrogen than with helium ions. Thus, several irregular and unexpected
      results were seen when the LET was increased.

PMID- 7501812
TI  - TLD postal dose intercomparison for megavoltage units in Poland.
AB  - The aim of the TLD pilot study was to investigate and to reduce the uncertainties
      involved in the measurements of absorbed dose and to improve the consistency in
      dose determination in the regional radiotherapy centres in Poland. The
      intercomparison was organized by the SSDL. It covered absorbed dose measurements
      under reference conditions for Co-60, high energy X-rays and electron beams. LiF
      powder type MT-N was used for the irradiations and read with the Harshaw TLD
      reader model 2000B/2000C. The TLD system was set up and an analysis of the
      factors influencing the accuracy of absorbed dose measurements with TL-detectors
      was performed to evaluate and minimize the measurement uncertainty. A fading not
      exceeding 2% in 12 weeks was found. The relative energy correction factor did not
      exceed 3% for X-rays in the range 4-15 MV, and 4% for electron beams between 6
      and 20 MeV. A total of 34 beams was checked. Deviation of +/- 3.5% stated and
      evaluated dose was considered acceptable for photons and +/- 5% for electron
      beams. The results for Co-60, high energy X-rays and electron beams showed that
      there were two, three and no centres, respectively, beyond acceptance levels. The
      sources of errors for all deviations out of this range were thoroughly
      investigated, discussed and corrected, however two deviations remained
      unexplained. The pilot study resulted in an improvement of the accuracy and
      consistency of dosimetry in Poland.

PMID- 7501813
TI  - Does the photon beam quality factor depend on the type of ionization chamber?
AB  - The photon beam quality factor Q of 6- and 15-MV photon beams has been measured
      using different types of thimble ionization chambers with various wall, electrode
      and insulator materials. Some types of chambers seem to overestimate the
      corresponding Q-value by 0.4% (6 MV) and 0.7% (15 MV), respectively. The effect
      on the stopping power ratio water to air and on the pertubation correction will
      be discussed.

PMID- 7501814
TI  - Salivary tissue of rhesus monkeys.

PMID- 7501815
TI  - Unexpected tumor response, radiation myelitis and increased in vitro-radio
      sensitivity of lymphocytes in a patient with non-small lung cancer.

PMID- 7501816
TI  - Interstitial brachytherapy for penile carcinoma: a multicentric survey (259
      patients).
AB  - Although cancer of the penis is a rare disease, we have collected 506 cases
      through a multicentric study. In the present study we analyse the results
      obtained from 259 patients treated by interstitial brachytherapy from 1959 to
      1989. Among the 259 patients, 184 males had exclusive brachytherapy (group A)
      while 75 received a combination of surgery and brachytherapy and/or external beam
      irradiation (EBI) (group B). Five- and 10-year survival rates are, respectively:
      overall survival, 66 and 52%; cause-specific survival, 88 and 88%; disease-free
      survival, 78 and 67%. One hundred and forty-three patients in group A (78%) and
      48 (64%) in group B avoided mutilation of the penis while late side effects
      occurred in 137/259 patients (53%). Survival depends on the volume of the tumor
      and the presence of involved nodes; systematic groin dissection does not however
      seem advisable.

PMID- 7501817
TI  - Radionecrosis of the mandibula: a retrospective analysis of the incidence and
      risk factors.
AB  - We analysed the incidence of a mandibular osteonecrosis (ON) in 189 patients
      irradiated for a cancer of the oral cavity, or of the oropharynx or epipharynx,
      with a total target dose of at least 60 Gy between 1980 and January 1994. Target
      doses per fraction were between 2.0 and 1.2 Gy, number of sessions per week was
      between 5 and 10, and total target doses were between 60 and 78.2 Gy. No instance
      of ON has been observed after target doses between 60 and 65 Gy. Cumulative
      incidence of an ON needing a mandibular resection was: 24.8% in patients treated
      with a mandibular dose per fraction between 2.00 and 2.22 Gy and a total
      mandibular dose between 66.00 and 79.70 Gy; 19.6% in patients treated with a
      mandibular dose per fraction between 1.80 and 1.90 Gy and a total mandibular dose
      between 69.00 and 75.60 Gy, 2.2% in patients treated with two fractions of 1.20
      Gy per day for 5 days in the week with or without simultaneous application of cis
      platinum and a total mandibular dose between 75.20 and 82.00 Gy. Dose per
      fraction, association of the tumour with bone, and the volume of the horizontal
      ramus of the mandibula irradiated with a high dose were observed to be
      significant risk factors.

PMID- 7501818
TI  - [A working hypothesis. Multiparameter functional imaging as a possible course for
      radiobiology].

PMID- 7501819
TI  - [The ethical and deontological aspects of quality inspection and control (QC) in
      imaging diagnosis. A problem too of professional training].
AB  - The major changes undergone by the health service structure in Italy have urged
      an organic and logical reconsideration of the relationship between health service
      resources and health needs, between competences and new patterns of organization.
      The primary units of the health service (USL), as actual enterprises, should
      undergo the control and rating of productivity and quality in the rational and
      fruitful use of available resources. The application of quality controls in
      health care (HCQC) to diagnostic imaging should be aimed at assessing of the
      performance of: the single procedures; the radiologist; the general practitioner
      or the non-radiologist specialist. These are obviously many indicators but the
      health care quality assessed by studying the structure of the process and of the
      result should not miss out: the sensitivity, specificity and diagnostic accuracy
      of the single imaging techniques; the ROC curves to assess the radiologist's
      performance; the predictive value, with known sensitivity and specificity, of the
      procedures, for the professional reliability of the non-radiologist physician. At
      present, QC indicators in diagnostic imaging cannot rule out the problem of a
      "radiologic training" of the non-radiologist physician to be able to correctly
      select the patients to be referred to diagnostic imaging. On the other hand, the
      radiologist should receive a "clinical training" for the rational use of the
      available techniques to address the clinical issues raised by the colleague,
      keeping in mind the cost-benefit factor. The "professional training" experience
      of the Istituto di Radiologia of the Universita Cattolica del Sacro Cuore is
      reported. The instruction of the undergraduate students from the training course
      of specialization follows two patterns of "objectives" and "problems". The
      trainee directly participates in a structure and productivity project playing a
      major role in the transition from the technological, organizing and functional
      approach to the clinical management of the patients. These changes cannot be
      separated from their ethical and deontological implications. The ethical issue
      begins at the patient's bedside and does not end with technical quality and
      feasibility, and with the economical opportunity in taking a precise legal and
      deontological responsibility.

PMID- 7501820
TI  - [Transient osteoporosis of the hip in magnetic resonance imaging].
AB  - This study was aimed at assessing the MR patterns of transient osteoporosis of
      the hip and, consequently, the role of MRI in the diagnosis and follow-up of this
      condition. Even though this condition was originally observed in pregnant women,
      young or middle-aged men are most frequently affected. There is a spontaneous
      onset of pain, usually progressing over several weeks. The patients have no risk
      factors for osteonecrosis; they may have a history of minor trauma and there is a
      possible relationship to the third trimester of pregnancy. Laboratory values are
      negative. Pain may be severe enough to cause the patient to limp and to impair
      joint function. The possible causes of transient osteoporosis have been debated
      by many authors and include trauma, synovitis, neurovascular dysfunction and
      transient or reversible ischemia. Transient osteoporosis is a self-limiting
      disease which does not require surgical treatment. The differential diagnosis of
      transient osteoporosis of the hip is very important because this condition may
      simulate cancer, septic arthritis, osteomyelitis or avascular necrosis. We report
      the initial and follow-up features of transient osteoporosis of the hip on the MR
      images of 6 patients (M/F = 5/1; age: 37-49 years, mean: 41.8 years). The right
      side was involved in 3 patients, the left side in 2 patients. The patient with
      bilateral transient osteoporosis was a woman in the 3rd trimester of pregnancy.
      In all patients, MRI was performed with an 0.5 T MR unit. The MR changes in our 6
      patients were rather uniform and included heterogeneous decrease in the signal
      intensity of the affected bone marrow on T1-weighted images and increased signal
      intensity on T2-weighted and STIR images, with no evidence of focal lesions. This
      pattern is known as the "bone marrow edema" (BME) pattern. All the patients
      received conservative treatment. The clinical symptoms and the MR abnormalities
      regressed completely within 6-10 months, with no late sequelae. To conclude, this
      follow-up MR study demonstrates the transient, reversible character of transient
      osteoporosis of the hip. Until the natural history of the BME pattern is better
      understood, we suggest a conservative management of this condition, especially in
      the patients with no risk factors for osteonecrosis. Radiographic and MR follow
      up is recommended.

PMID- 7501821
TI  - [The radiological assessment of the knee in the meniscectomy patient].
AB  - The increasing number of radiologic examinations performed on patients previously
      submitted to arthroscopic meniscectomy led us to analyze the types of lesion most
      frequently found in these patients and the prognostic factors related to
      meniscectomy. Thus, the radiographs, CT and MR examinations were reviewed of 34
      symptomatic patients submitted to arthroscopy at least 1 year earlier and in whom
      symptoms had appeared no more than 3 months earlier, thus ruling out the symptoms
      related to surgical complications. Lesions were found in the menisci, in the
      meniscal stumps and in the articular ends. The lesions involving the menisci not
      submitted to previous arthroscopy were not studied in detail. As to meniscal
      stumps, CT and MRI exhibited the same diagnostic accuracy, in detecting lesion
      recurrence, in 50% of cases. In the remaining cases their results were similar,
      with some false negatives (CT) and some false positives (MRI). As to
      osteoarthritis, MRI proved superior in detecting the microscopic evidence of
      cartilage-bone erosions even though 20% of patients exhibited findings of such
      entity as to be visible at CT. As regards the macroscopic evidence of articular
      ends deformity, CT and MRI yielded the same results. To define the prognostic
      factors of meniscectomy, all patient was asked to define their activity level
      after meniscectomy, that is before the onset or recurrence of symptoms. A
      detailed questionnaire was used to this purpose, using the Tapper-Hoover rating
      scale, expressly developed to derive a functional knee score after meniscectomy.
      The results indicate that the functional knee score (related to prognosis) was
      lower in patients older than 40, in meniscectomy performed in older age, in long
      intervals between trauma and meniscectomy, after complex and horizontal-cleavage
      lesions and, finally, in sedentary activity.

PMID- 7501822
TI  - [The role of magnetic resonance imaging with a low-intensity field (0.2 T) in
      assessing expansive lesions of the hand and wrist].
AB  - The diagnostic capabilities of a small-size low-field (0.2-T) MR unit with a
      dedicated coil were investigated in the study of expansive lesions of the hand
      and wrist. Twenty-five patients suffering from the following diseases were
      examined: synovial cyst (6 patients), ganglion cyst (4), acute suppurative
      tenosynovitis (3), stenosing tenosynovitis (2), arteriovenous fistula (1), lipoma
      (1), fibrolipoma (2), chondroma (1), glomus tumor (1), fibromatosis palmaris (3),
      villonodular synovitis (1). Spin Echo (SE) and Gradient Echo (GE) scans were
      performed on all patients. The MR findings were compared with US, surgical and
      pathologic results. In synovial and ganglion cysts, acute suppurative and
      stenosing tenosynovitis, fibromatosis palmaris, fibrolipoma and lipoma, MRI
      showed typical patterns. In arteriovenous fistula, chondroma, glomus tumor and
      villonodular tenosynovitis, an accurate diagnosis could not be made: in these
      cases US failed to yield unquestionable results and the lesions could be
      diagnosed only at pathology. MRI yielded very accurate information as to lesion
      site and relationship with the surrounding structures; this kind of information,
      which is extremely important for the surgical approach, is not always provided by
      US. Low-field MRI can be considered a valuable diagnostic tool in the study of
      some expansive lesions of the hand and wrist. In other lesions this method can
      play a major role for both their characterization and the surgical approach.

PMID- 7501823
TI  - [The role of the radiological hemithorax examination in closed trauma of the
      chest].
AB  - January, 1992, to September, 1994, a hundred and seventy-eight blunt chest trauma
      patients were examined with plain chest films and detailed rib studies. The
      patients were subdivided into three groups according to: a) the presence/absence
      of rib fractures correlated with clinical data; b) the depiction of rib fractures
      and/or thoracic complications; c) treatment customization in the presence/absence
      of rib fractures. In our series of patients the clinical data and the presence of
      rib fractures were poorly correlated. The detection rates of minor and major
      complications were also investigated on plain chest films and detailed rib
      studies. Plain chest films most frequently depicted the complications requiring
      conservative or surgical management and gave the indication for further imaging
      investigations. The detailed rib studies of the involved hemithorax yielded no
      further information useful to therapy except in few cases: and should therefore
      be limited to the cases exhibiting complications on chest films, which may
      benefit from surgical fixation. The accurate study of rib fractures is paramount
      in the cases where legal action may be undertaken.

PMID- 7501824
TI  - [Nonspecific osteomyelitis in childhood and adolescence. The contribution of
      imaging diagnosis].
AB  - Nonspecific osteomyelitis in children and adolescents can be diagnosed in
      patients 2 to 16 years old and may present as acute, subacute or chronic. During
      the last 9 years, 40 pediatric patients (aged 2 to 16 years) affected with extra
      axial inflammatory bone lesions were examined. The series of cases was then
      reviewed. This work was aimed at investigating the role of various imaging
      modalities: conventional radiology (CR), bone scan with technetium-99 methylene
      diphosphonate (99mTc-MDP), scintigraphy with technetium
      esamethylpropylenaminoxima labelled leukocytes (99mTc-HMPAO), computed tomography
      (CT) and magnetic resonance imaging (MRI) were used to detect the lesions, to
      make a differential diagnosis and to assess different disease stages. As for
      acute osteomyelitis (6 patients), CR showed a lytic lesion, periosteal new bone
      and soft tissue swelling in 4/6 patients; no abnormalities were demonstrated in
      the other two. Bone scan, CT and MRI depicted bone involvement. CT and MRI also
      showed inflammatory lesion spread to surrounding soft tissue. 99mTc-HMPAO
      scintigraphy was not performed in acute osteomyelitis, because of technical
      difficulties in performing the exam promptly; thus, the early diagnosis of lesion
      nature was made with bone biopsy. As for subacute osteomyelitis (23 patients),
      99mTc-HMPAO scintigraphy was performed in 8/23 patients and proved to be a highly
      sensitive method, showing cell clusters and confirming the diagnosis of
      inflammatory lesion. MRI showed a focal area of intermediate-low signal intensity
      on T1-weighted sequences, with small focal intralesional areas of low intensity,
      a low-signal perifocal rim and diffusely low signal of surrounding bone marrow.
      T2-weighted images showed high signal intensity in both the abscess lesion and
      bone marrow, the latter probably due to edema. In 5 patients, a paramagnetic
      contrast agent (Gd-DTPA) was administered during MRI and showed inhomogeneous
      enhancement of both the inflammatory lesion and surrounding bone marrow. As for
      chronic osteomyelitis (7 patients), MRI was performed in 5/7 patients. In 4
      patients the lesion appeared as a low-signal area on T1-weighted images while T2
      weighted images showed an inhomogeneous high-signal area. In the same patients,
      99mTc-HMPAO scintigraphy was always positive. In patient 5, the lesion was
      represented by a low-signal area on both T1 and T2-weighted images, while 99mTc
      HMPAO was negative. Therefore, in chronic osteomyelitis, both MRI and 99mTc-HMPAO
      were useful in detecting both spinal and peripheral bone involvement, which was
      in some cases asymptomatic at first observation CR, CT (3/4) and MR (4/4)
      findings extra-axial localizations were similar to those in subacute-chronic
      forms.

PMID- 7501825
TI  - [Magnetic resonance arthrography in chondral disease of the knee].
AB  - The clinical usefulness of Magnetic Resonance Imaging (MRI) of the knee in the
      depiction of meniscal, ligament and tendon lesions is well known. In contrast,
      the role MRI plays in the diagnosis of chondromalacia remains debated, the gold
      standard being arthroscopy. A new technique, i.e., MR arthrography (MRA), has
      been recently proposed which consists of the intraarticular injection of a
      paramagnetic contrast agent (Gd-DTPA) during MRI. Thirty-one patients with
      clinically suspected chondromalacia of the knee were examined with MRA. The exams
      were performed with a 1T superconductive magnet and a dedicated coil. All the
      patients were examined before (baseline scans) and after paramagnetic contrast
      agent injection. MRA results were compared with arthrographic findings. Baseline
      MRI had 25% sensitivity, 77.9% specificity and 83% diagnostic confidence in the
      diagnosis of chondromalacia; these figures increased to 93%, 97.6% and 91.5%
      after contrast agent injection. This preliminary experience confirms MRA to be a
      useful tool in the diagnosis of chondral knee conditions.

PMID- 7501826
TI  - [A comparison between endoral radiography and electronic magnification of digital
      orthopantomography].
AB  - We compared the electronic magnifications obtained from digital panoramic
      radiographs with intraoral radiographs with a new high resolution film. Fifty-two
      patients were submitted to both examinations--76 comparative studies and 217
      teeth studied in all. The two techniques appeared substantially comparable in
      terms of diagnostic effectiveness. The measurement of the alveolar ridge was
      strictly equivalent for the two examinations (< 1 mm disagreement in 80% of
      cases). The profile of lamina dura and the image of the radicular canal were
      better depicted with intraoral films. A useful advantage offered by digital
      images was the possibility of recognizing the soft tissues. In dental caries
      intraoral films was more effective than digital images and were correctly
      depicted small carious cavities (< 2 mm depth, 87 vs 74%). Digital panoramic
      radiography can be considered a promising alternative to panoramic film. Its
      electronic magnification may be a valuable diagnostic complement to intraoral
      films for the study of periodontal disease, but it cannot replace intraoral films
      for the assessment of fine dental details, small caries in particular. The new
      intraoral film was substantially equivalent to digital images for the assessment
      of bone lesions and of periodontal disease.

PMID- 7501827
TI  - [High-resolution computed tomography (HRCT) versus bronchoscopy in predicting the
      need for bronchial embolization in hemoptysis].
AB  - September, 1992, through May, 1994, thirty patients with hemoptysis were examined
      with CT, HRCT and bronchoscopy. Our study was aimed at comparing CT and HRCT with
      fiberoptic bronchoscopy in the identification and assessment of hemoptysis causes
      and of lesion shape and extent. These data are of basic importance for the
      interventional radiologist when an intravascular treatment is scheduled. The
      causes of hemoptysis included cystic fibrosis in 14 patients, bronchiectasis and
      bronchiolectasis in 11, tuberculosis in 3 and aspergillosis in one. In only one
      patient the etiology of hemoptysis remained undetected. Among the most common
      patterns, the "ground-glass" one was the main finding (50%), while bronchiectasis
      and bronchiolectasis were demonstrated in 40% of the patients. In the extent 10%
      of cases the cause of hemoptysis was identified with small lesions as a result of
      previous tubercular infections. Among the causes of hemoptysis, our study
      included only inflammatory, and not neoplastic, diseases. In 97% of patients, CT
      and HRCT allowed the diagnosis of lesion type, extent and site, while
      bronchoscopy did the same in only 35% of patients, because of its lack of
      accuracy in identifying and characterizing peripheral lesions. Our results
      suggest that CT and HRCT should be performed after bronchoscopy and before
      bronchial embolization. Confirming literature data, our study proves CT and HRCT
      to play a basic role in the diagnosis of the inflammatory conditions causing
      hemoptysis.

PMID- 7501828
TI  - [Magnetic resonance imaging in assessing the complications of cardiac surgery
      involving the ascending aorta].
AB  - Complications involving the ascending aorta after cardiac surgery are rare (<
      1%). Clinical findings are aspecific and may present a long time after surgery.
      Diagnostic imaging is used to show the type of complication and to provide
      adequate information for a suitable therapy. The authors investigated both
      efficacy and usefulness of MRI in the study of cardiac surgery complications
      involving the ascending aorta. Ten patients treated for heart disease were
      examined with MRI. Eight of them had had aortic valve replacement, 1 ascending
      aorta replacement and 1 both. Chest radiography and MRI were performed in every
      patient; 4 patients underwent transthoracic echocardiography (TTE) and
      transesophageal echocardiography (TEE), 2 patients TTE and 1 TEE; 2 patients were
      submitted to CT and 4 to angiography. MRI showed 3 ascending aorta aneurysms, 3
      dissecting aneurysms and 4 pseudoaneurysms. In the patients with aneurysms and
      dissecting aneurysms, MRI correctly demonstrated both the aneurysm and the
      intimal flap. MRI showed only large pseudoaneurysms, depicting mediastinal
      hemorrhage suggestive of pseudoaneurysm if the latter was small. In such cases,
      only angiography showed the breach site. In conclusion, MRI can be considered the
      method of choice to depict cardiac surgery complications involving the ascending
      aorta if aneurysms and dissecting aneurysms are present, because it yields enough
      information for both diagnosis and surgery. In contrast, in pseudoaneurysms or
      mediastinal hematomas angiography is necessary to show the exact rupture site of
      the aortic wall.

PMID- 7501829
TI  - [Restorative proctocolectomy. A morphological-functional study by computed
      tomography with coronal scans].
AB  - Restorative proctocolectomy with ileal pouch has become the surgical treatment of
      choice for patients with ulcerative colitis and familial polyposis of the colon.
      Defecography is the radiologic technique commonly used to obtain detailed
      information on function and morphology of the ileal pouch, but it fails to depict
      the pelvis. Computed Tomography (CT), with coronal images only was used to
      examine 10 patients with ulcerative colitis, submitted to restorative
      proctocolectomy. Coronal CT, yielding a panoramic view of the pelvis, represent
      an effective alternative technique to defecography. In fact, the two techniques
      provide comparable information relative to the ileal pouch; coronal CT also
      depicts the possible thickening of pouch walls and of pelvic fat tissue. Coronal
      CT also depicts the continence of ileo-anal and ileo-ileal anastomoses and the
      functional changes of the perineal muscles at rest and during squeezing. Coronal
      CT images allow easy and clear detection of such major postoperative
      complications as pelvic inflammation and fistulae (less frequently stenosis or
      dehiscences of the anastomosis).

PMID- 7501830
TI  - [The tissue characterization of focal liver lesions with magnetic resonance
      imaging].
AB  - This study was aimed at assessing the accuracy of Magnetic Resonance Imaging
      (MRI) in the characterization of focal liver masses. We prospectively examined 51
      patients with focal liver masses: the morphological features were investigated
      with different pulse sequences and the functional characteristics were studied
      after the i.v. administration of Gd-DTPA (2 mmol/kg). MR findings were compared
      with those of gold standard methods, i.e., percutaneous biopsy, surgery or, for
      hemangiomas, 99mTc-labelled blood cell liver scintigraphy. All hemangiomas
      presented with typical features: signal intensity was very high on long TE images
      (> 140 msec) and a globular enhancement pattern, with centripetal progression,
      was observed after dynamic studies. This signal pattern on T2-weighted images is
      highly indicative of hemangioma. Five of 7 focal nodular hyperplasias (71%) were
      isointense with hepatic parenchyma on all pulse sequences; the central scar was
      observed in 5/7 cases on short TR/TE images and in all cases on long TR/TE images
      in 16/17 cases (94%). High signal intensity on T1-weighted images was
      statistically significant for HCC. A pseudocapsule was observed in 12 cases
      (70%). A mosaic pattern on T2-weighted images was observed in 3 cases. Seventy
      four per cent of HCCs exhibited signal enhancement during the arterial phase of
      the dynamic study. Metastases presented a uniform pattern, i.e., they were
      hypointense on T1-weighted and hyperintense on T2-weighted images in 12/13 cases
      (92%). A central hypointense area on T2-weighted images is indicative of
      coagulative necrosis. A lesion with these morphological features and hypovascular
      signal is suggestive of metastasis.

PMID- 7501831
TI  - [Pancreatic assessment by magnetic resonance imaging: an improvement in the
      diagnostic results with new study technics].
AB  - Magnetic resonance imaging of the pancreas has been, limited by a series of
      artifacts with a resulting poor contrast to noise ratio. Nevertheless,
      technological progress has allowed to reduce not only scanning time but also the
      number of artifacts, by increasing the number of excitations and matrix size.
      Moreover, tissue contrast can now be modified. In our study performed on 5 normal
      volunteers and 20 patients with different pancreatic diseases conditions, fast SE
      sequences with and without fat suppression were used, with an overall increase in
      contrast to noise ratio. In all patients MR images allowed the accurate
      definition of the lesions: in 8 adenocarcinoma patients the lesion could be
      depicted, including the 2 lesions CT had poorly demonstrated. Also in the 3
      patients with endocrine tumors, MRI depicted small tumors which were later
      confirmed at surgery. This new protocol makes MRI a very sensitive and accurate
      tool in the study of neoplastic and inflammatory pancreatic diseases thus, MRI is
      not only a complementary tool to CT but an even better study technique. In
      particular, its higher contrast to noise ratio allows a dramatic improvement in
      the depiction of small solid lesions, especially those not altering pancreatic
      outline. This study proves that MRI, when adequately performed, is a very
      accurate tool to study, in a very short time, the pancreas and peripancreatic
      region, yielding much better results than all the other diagnostic imaging
      modalities.

PMID- 7501832
TI  - [The volumetric changes of uterine myomas in pregnancy].
AB  - Thirty-six pregnant women with a single uterine myoma were submitted to US at 2
      and 4 weeks' intervals. The first US examination was made in 12 patients before
      pregnancy and in the other 24 patients between 9 and 12 weeks' gestation. The
      changes in the volume of myomas were analyzed in different periods of pregnancy.
      Thirty-four women underwent US in puerperium, four weeks after delivery: the
      myomas were smaller, possibly back to their initial volume. In 11 patients
      (31.6%), the myomas grew bigger during pregnancy, particularly during the first
      trimester. A statistically significant change in volume was observed between the
      first and the third trimester of pregnancy (p < 0.001). When investigating myoma
      growth in greater detail in the first trimester, we observed that the greatest
      increase in myoma volume occurred before the 10th gestational week. Three
      different categories of myoma volume were considered (p < 100 cc, 100-200 cc, >
      200 cc) and related to myoma growth in each period. No relationship was observed
      between myoma volume and myoma growth.

PMID- 7501833
TI  - [Echo-Doppler in chronic kidney transplant rejection. The diagnostic prospects
      using indices of the ascending systolic phase].
AB  - To date, Doppler US has been rarely used to diagnose chronic renal transplant
      rejection because of its low sensitivity. Nevertheless, all the results have been
      obtained from the analysis of flow-metric indices, mainly considering the
      diastolic phase of the Doppler waveform, e.g., the resistance index (RI) and the
      pulsatility index (PI). This study was aimed at investigating if Doppler
      diagnostic accuracy in renal transplant monitoring can be increased by studying
      the systolic phase, considering peak arterial systolic velocity (Vp),
      acceleration time (AT) and acceleration index (AI). Seventy-six renal transplant
      recipients were examined with color-Doppler and duplex Doppler US, which showed
      47 well-functioning and 29 hypofunctioning kidneys. The diagnosis was confirmed
      with perfusion scintigraphy with 99mTc DTPA, biopsy and 6-month clinical
      laboratory follow-up. The means of Vp, AI, AT and RI relative to the group of
      patients with normal renal function were compared with those in the group of
      patients with chronic rejection. Critical values were measured at the segmental
      arteries (Vp = 70 cm/s, AI = 7 m/s2, AT = 100 ms), at the interlobar arteries (Vp
      = 45 cm/s, AI = 4 m/s2, AT = 100 ms) and at the arcuate arteries (Vp = 35 cm/s,
      AI = 3 m/s2, AT = 100 ms). On the basis of these values, normal functioning
      transplants were differentiated from hypofunctioning ones. RIs were altered (>
      0.75) in 8 of 17 chronic rejections and in 3 of 47 normal transplants, with 47.1%
      sensitivity and 93.6% specificity. The combination of RI with Vp and AI strongly
      increased both sensitivity (100%) and specificity (82.98%). Combined AI and RI
      exhibited 94.1% sensitivity and 89.3% specificity. In conclusion, the indices of
      the ascending systolic phase, in peripheral vascular samplings, are clearly more
      efficacious than RI alone and index combination exhibits the highest diagnostic
      accuracy.

PMID- 7501834
TI  - Ultrasonography endometrial patterns in different hormonal treatments to induce
      ovulation.
AB  - As several studies report that transvaginal ultrasound of endometrial thickness
      may help distinguish fertile from infertile cycles, we assessed endometrial
      growth and morphology in 124 infertile women. The patients underwent different
      ovulation induction treatments: clomiphene citrate (CC), human menopausal
      gonadotropin (hMG) and human chorionic gonadotropin (hCG), analogous Gn-RH and
      hMG (aGn-RH+hMG). CC administration is followed by a slackening of endometrial
      maturation. The US pattern H (typical of the ovulatory phase) appears on day 13
      (76.9% of the cases) in spontaneous cycles and on day 16 (75% of the cases) in CC
      induced cycles. The H pattern on day 20 in CC-induced cycles persisted in the
      patients who did not conceive. In aGn-RH-stimulated cycles the endometrial
      pattern H appears on days 13 (41.66%) and 16 (83.33%), not preceded by a Hi
      image. The endometrial pattern Hi was always observed in the patients who did not
      conceive. Our retrospective study of endometrial US morphology shows that the
      different ovulation induction treatments may affect the day of appearance of the
      various endometrial patterns. These results, which need further confirmation, can
      allow the changes of conceiving to be investigated during the stimulation
      protocol of every single stimulated cycle.

PMID- 7501835
TI  - [The diagnostic reliability of percutaneous biopsy specimens obtained under
      instrumental guidance using 4 different types of needles].
AB  - To assess if the effectiveness of biopsy sampling, whose usefulness is widely
      recognized, can be influenced by different cutting mechanisms, we compared four
      different types of needles (A, B, C, D) in 76 patients, each needle being of the
      same length (15 cm) and calibre (18 G) but with different tip shapes. Forty
      biopsy samples were obtained with each type of needle for a total of 160 samples
      in 76 patients; 61 samples were acquired under CT guidance and 99 under US
      guidance. The results were subdivided in 6 categories based on biopsy result: PI
      (diagnosis histotype in malignant lesions), PN (diagnosis of malignancy in
      neoplastic lesions), P (correct diagnosis in benign lesions), S (suspicion of
      neoplastic lesion), E (misdiagnosis), NI (insufficient material). The results,
      respectively, for each needle type are: 32.5%, 30%, 2.5%, 7.5%, 12.5% and 15%
      with needle A; 35%, 30%, 7.5%, 0%, 15% and 12.5% with needle B; 27.5%, 17.5%,
      10%, 7.5%, 22.5% and 15% with needle C; 30%, 15%, 7.5%, 15%, 17.5% and 15% with
      needle D. The sensitivity and specificity for each needle type were,
      respectively, 84.4% and 85.29% for needle A; 86.66% and 88.57% for needle B; 70%
      and 73.52% for needle C; 77.41% and 79.41% for needle D. No statistically
      significant difference was found in the effectiveness of the four needles (chi
      2); on the contrary, lesions's size can affect sampling quality.

PMID- 7501836
TI  - [Nonvascular interventional radiology in the treatment of post-liver transplant
      complications. The clinico-radiological correlations and technical
      considerations].
AB  - Eleven patients, included in a series of 105 orthotopic liver transplant
      recipients, underwent interventional radiologic procedures for post-operative
      complications. Seven patients had obstructive jaundice, three patients had
      sepsis, and one patient was bleeding from the T-tube. Cholangiography, performed
      in 9/11 patients, demonstrated stenosis of the anastomosis in six cases, stenosis
      of the intrahepatic biliary tree in one case, and stenosis of both tracts in the
      remaining two cases. Four patients were treated with bilioplasty (from 1 to 5
      sessions), using balloon catheters (8-10 mm) followed by stones removal in one
      case, and by the placement of a metallic stent in another case. The follow-up
      ranged from one to three years: no biliary stasis occurred, during that period,
      in these patients. Another patient with recurrent cholangiocarcinoma of the
      biliary anastomosis, treated with Carey-Coons endoprosthesis and brachytherapy,
      died four months later without jaundice. In the three patients with sepsis and in
      the patient with bleeding from the T-tube, intra- or extra-hepatic (in one case)
      multiple abscesses were demonstrated. The conservative treatment with the
      placement of percutaneous drainage catheters, associated with internal biliary
      drainage in two cases, allowed complete symptoms resolution. The technical
      success obtained in all patients confirmed the effectiveness of interventional
      radiology in the treatment of biliary complications after liver transplant, thus
      avoiding the need of surgical reintervention.

PMID- 7501837
TI  - [The spatial resolution of the digital storage phosphor system. The monitor and
      film compared].
AB  - The physical characteristics of radiographic images, namely spatial resolution
      and contrast, have obvious effects upon diagnostic image usefulness. We
      investigated the spatial resolution of both radiographs and magnified digital
      obtained with a storage phosphor system, in comparison with a film-screen
      combination. This study was carried out on the conventional radiographs of a
      phantom grid 0.5 mm thick, with resolution ranging from 0.5 to 10 lp/mm. Each
      examination was compared at naked eye and with the electronic evaluation of a
      region of interest on both standard and magnified views or by digitization with a
      charge coupled detector (CCD) television camera followed by the computing of the
      modulation transfer function curve. Our results demonstrate a higher spatial
      resolution of direct magnification, on both digital and film-screen pictures
      (over 5 lp/mm). On the contrary, the electronic magnification on the monitor
      yields the same spatial resolution as non-magnified digital images (up to 4.3
      lp/mm). By selecting appropriate regions of interest, we could demonstrate the
      compression of the non-magnified images on the monitor. The modulation transfer
      curves show that direct magnification yields higher spatial resolution than
      electronic magnification and non-magnified views. Viewing electronically
      magnified images on the monitor yields the same resolution as contact
      radiographs: the monitor offers the advantage of an easier study of the regions
      of interest.

PMID- 7501838
TI  - Wedge factor changes with depth and field size on a linear accelerator with a
      motorized wedge.
AB  - The wedge factor was experimentally determined as a function of field size and
      phantom depth for 6-MV X-rays; measurements were performed on a linear
      accelerator with a motorized wedge filter (universal wedge, nominal wedge angle =
      60 degrees). As a result of our experimental work, we can state that: 1) The
      wedge factor increases linearly with phantom depth (0.275%/cm), almost
      independent of field size; this change was experimentally related to the beam
      "hardening" caused by the high Z value of wedge material, as shown by the
      increase in wedged-field PDD with respect to the corresponding open-field PDD.
      Neglecting this variation can induce systematic errors in delivered dose,
      especially when deep-seated tumors are treated with wedge fields. 2) The wedge
      factor changes, for rectangular fields, according to the "equivalent square law",
      and not to the dimension in the wedged direction.

PMID- 7501839
TI  - [The results of sandwich adjuvant radiotherapy in 2nd- and 3rd-stage rectal
      adenocarcinoma. The authors' personal experience].
AB  - From January, 1985, to June, 1993, 125 patients with stages B2-C adenocarcinomas
      of the rectum were submitted to pre- and postoperative irradiation according to
      Thomas Jefferson University protocol guidelines. Five hundred cGy were
      administered as a single preoperative dose 24 hours before surgery using parallel
      opposed (AP-PA) treatment fields including the whole pelvis. Pathologic samples
      were classified following the Astler-Coller staging criteria. Forty-seven
      patients had no postoperative treatment because their disease stage was A, B1 or
      D, 11 for refused consent and 9 postoperative complications preventing any
      further therapy. Seventy-eight patients concluded the treatment schedule and are
      assessable for response. Radiotherapy total dose consisted of 4400-5000 cGy
      administered over 5-6 weeks: the patients were treated with megavoltage photons
      (15-MeV photons) and one dose fraction of 2 Gy was delivered daily, 5 days a
      week, with the "box" or the "three-field" technique. Median follow-up time was
      50.2 months from the beginning of treatment for all the patients in our series
      (range: 18-120 months). Radiation therapy was well tolerated: 5 patients had
      severe diarrhea and 2 had small bowel obstruction which required surgery. Local
      recurrences were observed in 13 of 78 patients (16.7%). Overall actuarial
      survival at 5 years was 66.8%. Our results confirm the efficacy of this
      treatment, which is in agreement with international literature data. However, no
      difference was seen relative to the results obtained with postoperative
      irradiation alone. We conclude that sandwich radiotherapy can be an effective
      tool for the local control of rectal adenocarcinoma, with acceptable morbidity,
      even though it fails to prevent metastases.

PMID- 7501840
TI  - [The Ellis-van Creveld syndrome. A case report].

PMID- 7501841
TI  - [The Mounier-Kuhn syndrome (tracheobronchomegaly). The diagnostic role of
      computed tomography].

PMID- 7501842
TI  - [An intramural hematoma of the ascending aorta. The radiological trap].

PMID- 7501843
TI  - [The integrated imaging of a rare case of partial anomalous pulmonary venous
      connections].

PMID- 7501844
TI  - [The imaging diagnosis of primary hyperparathyroidism due to parathyroid
      adenocarcinoma. A case report].

PMID- 7501845
TI  - [Non-Hodgkin's lymphoma of the large intestine in an HIV-positive hemophiliac. A
      report of a case with an unusual presentation].

PMID- 7501846
TI  - [An echotomographic study of a case of polyorchidism].

PMID- 7501847
TI  - [The use of self-expanding stents in the recanalization of gastric antrum
      neoplastic obstructions. The experience of a case].

PMID- 7501848
TI  - [Retrobulbar orbital dirofilariasis. A case report].

PMID- 7501849
TI  - Sonography of the umbilical cord.
AB  - Knowledge of the development, normal sonographic appearance, and potential
      abnormalities of the umbilical cord is important in fetal assessment. The
      umbilical cord can be visualized throughout most of gestation and is detectable
      sonographically soon after visualization of the fetal pole. The normal umbilical
      cord is 50-60 cm long and may coil as many as 40 times, usually to the left.
      Abnormalities in umbilical cord size, degree of coiling, attachment, and position
      can have important implications for the outcome of the pregnancy. Structural
      abnormalities of the umbilical cord such as single umbilical artery, knots,
      cysts, and tumors may be associated with fetal distress or malformations. Color
      Doppler ultrasound (US) is useful in the identification and evaluation of
      structural abnormalities of the cord. By allowing measurement of blood flow
      velocity in the umbilical artery, duplex Doppler US may provide additional
      information in the evaluation of intrauterine growth retardation and twin-twin
      transfusion syndrome.

PMID- 7501850
TI  - Imaging the effects of diabetes on the genitourinary system.
AB  - Diabetes mellitus is a common multisystemic disease with serious effects on the
      genitourinary system. In the radiology literature, little attention has been paid
      to developing an integral approach to imaging of the genitourinary tract in
      diabetes. The long-term effects of diabetes on the genitourinary system include
      diabetic nephropathy, papillary necrosis, renal artery stenosis, diabetic
      cystopathy, and vas deferens calcification. Diabetes-associated urinary tract
      infections include renal and perirenal abscesses, gas-forming infections such as
      emphysematous pyelonephritis and emphysematous cystitis, fungal infections, and
      xanthogranulomatous pyelonephritis. Diabetes-associated genital infections
      include Fournier gangrene and postmenopausal tubo-ovarian abscess. In a diabetic
      with fever of unknown origin or in the event of a persistent infection in a
      diabetic with clinical deterioration despite use of antibiotics, radiologic
      studies can demonstrate the presence of genitourinary complications. Finally,
      radiologists should be aware of the risk of contrast material-induced nephropathy
      in diabetics.

PMID- 7501851
TI  - The CT nephrogram: implications for evaluation of urinary tract disease.
AB  - The urographic nephrogram is an important indicator of underlying functional and
      structural renal disease. With expansions in use of cross-sectional imaging, the
      computed tomographic (CT) nephrogram (ie, contrast material enhancement within
      the renal parenchyma) has assumed a greater role in the evaluation of urinary
      tract disorders. Both quantitative and qualitative nephrographic abnormalities
      are well demonstrated by CT, including global or segmental absence or persistence
      of the nephrogram, slowed temporal progression, striated pattern, and rim
      pattern. Global absence is nearly always unilateral and is most often seen with
      blunt abdominal trauma with renal pedicle injury. Segmental absence is
      attributable to focal renal infarction, most likely due to arterial emboli.
      Global persistence, which is much more common than segmental persistence, may be
      unilateral (caused by renal artery stenosis, renal vein thrombosis, or urinary
      tract obstruction) or bilateral (due to systemic hypotension, intratubular
      obstruction, or abnormalities in tubular function). Striated nephrograms may be
      unilateral or bilateral and are caused by ureteric obstruction, acute
      pyelonephritis, contusion, renal vein thrombosis, tubular obstruction,
      hypotension, and autosomal recessive polycystic kidney disease. The rim pattern
      is most often associated with renal infarction and occasionally with acute
      tubular necrosis and renal vein thrombosis. Careful evaluation of the CT
      nephrogram is an integral part of the abdominal CT examination.

PMID- 7501852
TI  - Straight border sign of the liver: spectrum of CT appearances and causes.
AB  - Attenuation differences bordered by straight lines within the liver (the straight
      border sign) are sometimes seen at computed tomography (CT). This phenomenon,
      which was demonstrated with unenhanced CT over a dozen years ago, does not
      represent a hepatic mass and is often associated with vascular compromise. Major
      causes of the straight border sign include fatty liver, confluent fibrosis,
      radiation hepatitis, and vascular abnormalities such as tumor thrombus,
      thromboembolus, compression, and arterioportal shunt. The frequency of this
      finding increases when intense contrast enhancement is used, especially when
      contrast material is administered via the superior mesenteric artery (CT during
      arterial portography) or hepatic artery (CT arteriography). The use of spiral CT
      is apparently increasing the chances of encountering this sign in daily practice.
      To correctly interpret the straight border sign, one should consider the
      distribution (anatomic vs nonanatomic), the attenuation (low vs high), and the
      use and technique of contrast enhancement.

PMID- 7501853
TI  - Doppler US of helical flow in the portal vein.
AB  - In helical portal venous blood flow, the usual laminar flow in the portal vein is
      replaced by a spiral. This changes the color Doppler ultrasound (US) appearance
      to one of alternating or parallel red and blue bands. Duplex US may appear to
      show hepatopetal, hepatofugal, or simultaneous bidirectional flow depending on
      placement of the cursor within the helix. Helical portal venous flow is unusual
      in normal individuals (2.2% of 135 patients). Its presence should prompt further
      scrutiny for signs of liver disease, particularly portosystemic shunts, as in 20%
      of 41 patients who subsequently underwent liver transplantation. It is a normal
      finding immediately after liver transplantation (43% of 35 patients) and
      transjugular intrahepatic portosystemic shunt (TIPS) creation (28% of  36
      patients). In both liver transplant and TIPS recipients, helical flow is usually
      transient. Its persistence long after transplantation in association with a
      prolonged increase in portal venous velocity is a useful sign of portal vein
      stenosis. Helical flow may also occur in cases of neoplastic invasion or
      displacement of the portal vein.

PMID- 7501854
TI  - CT of the esophagus: spectrum of disease with emphasis on esophageal carcinoma.
AB  - The esophagus is involved by a wide range of pathologic processes that can be
      detected, defined, and staged with computed tomography (CT). These processes
      include esophageal carcinoma; benign esophageal tumors; inflammatory and
      infectious diseases; miscellaneous conditions such as Barrett esophagus,
      achalasia, and varices; and trauma and perforation. CT is usually performed to
      clarify findings seen with other imaging modalities or to stage a pathologic
      condition; however, it may be the primary imaging modality in some cases. Because
      of the critical location of the esophagus, it can be involved secondarily by
      other disease processes or as part of a systemic process. By being aware of the
      appearances of the various entities that affect the esophagus, the radiologist
      can play an important role in detecting and staging esophageal disease. Although
      the role of CT in the evaluation of esophageal disease has been controversial,
      recent developments such as spiral CT have the potential to renew interest in
      this application.

PMID- 7501855
TI  - Langerhans cell histiocytosis: presentation and evolution of radiologic findings
      with clinical correlation.
AB  - Radiologic images and medical records of 42 children with Langerhans cell
      histiocytosis (LCH) (histiocytosis X) were reviewed to evaluate the presentation
      of the disease and the evolution of the radiologic findings. There were 26 male
      and 16 female patients aged 3 months to 18 years. Twenty-two patients presented
      with localized disease; 20 presented with multifocal disease. Four patients
      developed diabetes insipidus. Two patients had organ dysfunction. The radiologic
      findings were largely due to destructive bone lesions; 83% of the patients had at
      least one affected bone. Isolated soft-tissue masses, interstitial lung disease,
      and central nervous system abnormalities were also seen. Of patients in whom
      results of appropriate follow-up were available, 91% showed improvement in their
      lesions, 43% developed new lesions, and 92% had good clinical outcomes. LCH is
      usually a self-limited disease with a varied clinical and radiologic
      presentation. The prognosis is generally poor in children with organ dysfunction.
      In the absence of organ dysfunction, children with either localized or multifocal
      LCH have an excellent prognosis.

PMID- 7501856
TI  - SAPHO syndrome.
AB  - Palmoplantar pustulosis and severe acne are sometimes associated with peculiar
      aseptic skeletal conditions, but such skeletal lesions can be found without skin
      lesions. The term SAPHO syndrome has been coined for this cluster of
      manifestations. (The acronym SAPHO refers to synovitis, acne, palmoplantar
      pustulosis, hyperostosis, and osteitis.) The most common site of the disease is
      the upper anterior chest wall, characterized by predominantly osteosclerotic
      lesions, hyperostosis, and arthritis of the adjacent joints. Osteosclerosis of
      the vertebral bodies, hyperostosis, and erosions of the vertebral plates can be
      encountered. Unilateral sacroiliitis is frequently observed. Long bone
      involvement consists of osteosclerosis or osteolysis with periosteal new bone
      formation. Peripheral arthritis can be present but is rarely associated with
      joint destruction. The pathogenesis of this syndrome remains unknown, but a link
      with seronegative spondyloarthropathies is probable. Radiologists should be aware
      of this unusual syndrome to avoid misdiagnosis (eg, tumor, infection),
      unnecessary surgery, and antibiotic therapy.

PMID- 7501857
TI  - Gastrointestinal manifestations of acquired immunodeficiency syndrome: radiologic
      pathologic correlation.
AB  - Gastrointestinal diseases are common in patients with the acquired
      immunodeficiency syndrome (AIDS). In this review, the radiologic and pathologic
      findings of these diseases in AIDS patients are illustrated with cases from the
      archives of the Armed Forces Institute of Pathology. Diseases are categorized in
      two etiologic groups, opportunistic infections and AIDS-related neoplasms.
      Opportunistic infections include those caused by viral, fungal, protozoan, and
      bacterial pathogens. The AIDS-related neoplasms of primary importance are Kaposi
      sarcoma and non-Hodgkin lymphoma. The radiologic findings of these
      gastrointestinal diseases are frequently nonspecific. However, interpretation of
      the images with knowledge of the underlying pathologic entities and the level of
      compromise of the immune system helps narrow the differential diagnosis and often
      helps identify the presumptive diagnosis.

PMID- 7501858
TI  - The AAPM/RSNA physics tutorial for residents. Physics of PET.
AB  - Positron emission tomography (PET) is a coalition of physics, chemistry,
      physiology, and medicine united in an effort to measure physiologic parameters
      noninvasively. A PET study consists of producing radiotracers, synthesizing
      radiopharmaceuticals from the tracers, administering the radiopharmaceutical to a
      patient, measuring the resulting radioactivity distribution in an organ of
      interest, and interpreting the activity distribution as a function of physiologic
      parameters. Radiotracers are produced with medical accelerators that are
      characterized by the amount of time required to produce a set amount of
      radiotracer. Radiopharmaceutical production requires automated or remote
      synthesis modules that are characterized by their efficiency for incorporating
      the radiotracer into a radiopharmaceutical and the length of time and amount of
      human interaction required. Imaging protocols must consider sources of image
      artifacts, the method by which the images will be analyzed, and the uncertainty
      in the final result. Each of these areas has implications for the cost of the
      procedure, patient comfort, and the information obtainable from the study. This
      article gives an overview of these areas and defines the principles that can be
      used to distinguish between and the consequences of different approaches.

PMID- 7501859
TI  - A method for practical equalization mammography of the radiographically dense
      breast.
AB  - It has been shown that equalization radiography can overcome the well-known
      problem of limited film latitude encountered in mammography of the
      radiographically dense breast. Current equalization geometries based on single
      scanning beam (SER) or multiple-beam techniques approach the heat-loading limits
      of mammographic x-ray sources and require excessively long scan times. The
      authors have proposed an alternative geometry for equalization mammography,
      rotary scanning equalization radiography (RSER), which uses a slot beam in a
      translate-rotate geometry. RSER provides the simplicity of a single-beam geometry
      while offering improved tube efficiency over multiple-beam geometries. Numerical
      simulations and a prototype imaging system are used to show that equalized
      mammograms exhibiting high contrast throughout the breast can be obtained with a
      large scanning beam translated over the image at only four scanning angles. These
      results indicate that RSER is an efficient, simple, and practical means of
      imaging the dense breast.

PMID- 7501860
TI  - Computer-based radiology information system: from floppy disk to CD-ROM.
AB  - The authors have developed a comprehensive computer-based radiology information
      system known as "Radiology Resource and Review" (R3). The content is divided into
      10 radiology information categories spanning the entire human body and presently
      includes more than 4 Mbytes of text, 9,000 topics, and 6,000 images. The R3
      software and the information content are stored on compact disk, read-only memory
      (CD-ROM) media. The images are compressed by using a standard compression
      algorithm. Images and text are cross-indexed with more than 13,000 key words,
      which can be linked together in searches by using Boolean logic. Four different
      retrieval interfaces support browsing of text and image information, diagnosis
      decision making, self-study, and teaching file preparation. The 10-year
      university-funded evolution of R3 is an example of the transition in storage
      media from floppy disk to CD-ROM.

PMID- 7501861
TI  - Pediatric case of the day. Malignant fibrous histiocytoma (MFH) of the left
      atrium.

PMID- 7501862
TI  - General case of the day. Myxoid chondrosarcoma of the cavernous sinus.

PMID- 7501863
TI  - US case of the day. Occlusion of the CCA with segmental reversal of ECA flow and
      a patent ICA.

PMID- 7501864
TI  - Radiologic history exhibit. The contribution of fundamental discovery to the
      emergence of nuclear medicine as a discipline.

PMID- 7501865
TI  - Measurements of environmental lead contamination and human exposure.
AB  - The importance of accurate measurements of environmental lead exposure and
      toxicity is substantiated by analyses documenting the global contamination of the
      biosphere with industrial lead and the pervasiveness of measurable lead toxicity
      in human populations. Those data demonstrating environmental lead contamination
      and toxicity have, in part, led to regulations that limit the amount of lead in
      some products (e.g., paint, solder, and gasolines) in many industrialized
      countries. These regulations have resulted in a substantial reduction in some
      lead discharges to the environment. In spite of these reductions, current
      environmental lead levels are still often more than 10-fold, and sometimes more
      than 10,000-fold, higher than natural levels. Further, environmental lead
      concentrations are expected to remain elevated for a protracted period due to
      continued emissions of relatively large amounts of industrial lead to the
      environment and the persistence of contaminant lead in the environment.
      Discharges of contaminant lead have resulted in increases in organism and human
      lead levels comparable to increases documented in environmental matrices, as
      indicated by a recent estimate of the natural level of lead in blood of
      preindustrial humans (0.016 microgram/dL or 0.8 nM). This estimate is 175-fold
      lower than average blood lead levels in the United States (2.8 micrograms/dL or
      140 nM) and 600-fold lower than the recently (1991) revised Centers for Disease
      Control (CDC) action level of concern for early toxic effects in children (10
      micrograms/dL or 480 nM). The significance of these comparisons to public health
      is corroborated by numerous studies suggesting that there may be no lower
      threshold for sublethal toxicity in contemporary (i.e., lead-contaminated)
      humans. Those data also indicate that environmental lead concentrations that were
      previously considered innocuous may be deleterious to human health. It is
      apparent that the extent of sublethal lead toxicity in humans may be best
      addressed by studies that consider control populations possessing natural (i.e.,
      preindustrial) lead burdens, as well as state-of-the-art, trace-metal-clean
      techniques and advanced instrumentation. Trace-metal-clean techniques are
      required to prevent the inadvertent lead contamination of samples, which has
      plagued many previous analyses of environmental and human lead levels. Advanced
      instrumentation is required to provide the sensitivity, accuracy, and precision
      that are needed to quantify the sublethal effects of lead concentrations at
      environmental levels of exposure. Fortunately, methodologies utilizing these
      advancements are now capable of addressing many of the important issues (e.g.,
      lead biomolecular speciation, low exposure effects) in environmental and human
      lead toxicology.

PMID- 7501866
TI  - Epidemiology of atrazine.
AB  - Chronically exposed workers in chemical plants have revealed no increased
      incidence of benign or malignant disease attributable to atrazine. Some case
      control studies showed a slight increase of non-Hodgkin's lymphoma (NHL)
      incidence while others were negative. Weighted evidence supports no causal
      association of malignant changes in farming populations with atrazine. Two
      studies on a rural population suggested an increase of ovarian tumors in exposed
      women. Neither statistics nor exposure data are satisfactory, however, and no
      other studies present supporting evidence. New studies under clearly defined
      conditions are desirable. Very high doses of atrazine ingested in suicidal
      attempts had no acute clinical effect, suggesting that atrazine is virtually
      innocuous to humans. Sporadic reports on suspected acute poisoning leave too many
      questions open to be convincing: they reflect coincidence rather than causality.
      The tolerance of ruminants to triazine is limited. Severe poisoning in case of
      accidental intake of concentrated products is to be expected. Poisoning through
      ingestion has been controlled with activated charcoal. Adsorption on fodder
      enhances tolerability of triazines. Suspected poisoning through spray
      contaminated fodder requires differential diagnosis to avoid confusion with other
      pasture toxins, electrolyte problems, or gastrointestinal infection.

PMID- 7501867
TI  - Exposure of children to pollutants in house dust and indoor air.
AB  - This review summarizes occurrence and exposure studies for pollutants in house
      dust and related indoor air exposures. A standard sampling method and control
      methods to reduce these exposures are discussed, including recommendations for
      future research. Infants and toddlers receive a broad and significant range of
      exposures to lead, pesticides, PAHs, allergens, and VOCs in house dust and indoor
      air. Carpet dust in eight Columbus and nine Seattle homes contained
      concentrations of potentially carcinogenic PAHs ranging from 3 to 290
      micrograms/g, of lead from 250 to 2250 micrograms/g, and of PCBs from 210 to 1900
      ng/g. Dust collected from ten used sofas in Seattle averaged 16.3, 37.2, and 229
      micrograms/g for dust mite allergen, cat allergen, and lead, respectively; dust
      samples showed mutagenic activity. Biological and chemical pollutants in indoor
      dust and air have been associated with lead poisoning, cancer, allergy, asthma,
      damage to the nervous system, and sick building symptoms. The 11% of toddlers who
      have pica tend to have the highest exposures and risks. Further, the exposure of
      toddlers to lead via the dust pathway can be greater than by other routes.
      Standard method ASTM 5438.94 for sampling house dust has been used to
      characterize current and chronic exposure of toddlers in epidemiological studies.
      The accumulation of dust, dust mites, and tracked-in soil in old carpets, sofas,
      and mattresses appears to be a major source of exposure to lead, pesticides,
      allergens, PAHs, and VOCs. Remodeling and energy conservation can reduce
      ventilation and increase relative humidity, dust, dust mites, molds, VOCs, and
      other indoor air pollutants. The U.S. faces large and increasing costs from
      asthma and allergy. Asthma incidence in the U.S. has increased from 0.5% in 1930
      to 8%-12% in 1991. Asthma hospitalization rates for children are increasing at
      the rate of 4%/yr in the U.S. and 14%/yr in Seattle. Such hospital visits would
      be rare with effective diagnosis, patient education, and control of home
      exposures. Asthma was estimated to cost $6.2 billion in 1990; hospital visits of
      children in Seattle cost $2,526,000 in 1993. Forty percent of the U.S. population
      has been sensitized to allergens; one in three homes has high relative humidity,
      which favors dust mites, molds, allergies, asthma, and other respiratory
      diseases. Reducing indoor allergens can reduce costs, severity, and the risk of
      being sensitized and developing allergic disease. Use of volunteer Master Home
      Environmentalists to do free in-home surveys and education in Seattle may reduce
      immediate health costs from allergens as well as long-term risks from lead,
      carcinogens, and home chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7501868
TI  - Bioaccumulation of polycyclic aromatic hydrocarbons by marine organisms.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the marine environment,
      occurring at their highest environmental concentrations around urban centers.
      While they can occur naturally, the highest concentrations are mainly from human
      activities, and the primary sources are combustion products and petroleum. Two
      factors, lipid and organic carbon, control to a large extent the partitioning
      behavior of PAHs in sediment, water, and tissue; the more hydrophobic a compound,
      the greater the partitioning to these phases. These two factors, along with the
      octanol-water partition coefficient, are the best predictors of this partitioning
      and can be used to determine PAH behavior and its bioavailability in the
      environment. It is well known that the lipid of organisms contains the highest
      levels of hydrophobic compounds such as PAHs, and that organic carbon associated
      with sediment or dissolved in water can have the greatest influence on PAH
      bioavailability. Partitioning of combustion-derived PAHs between water and
      sediment may be much less than predicted, possibly because associations with
      particles are much stronger than expected. This reduced partitioning may produce
      erroneous results in predicting bioaccumulation where uptake from water is
      important. Accumulation of PAHs occurs in all marine organisms; however, there is
      a wide range in tissue concentrations from variable environmental concentrations,
      level and time of exposure, and species ability to metabolize these compounds.
      PAHs generally partition into lipid-rich tissues, and their metabolites can be
      found in most tissues. In fish, liver and bile accumulate the highest levels of
      parent PAH and metabolites; hence, these are the best tissues to analyze when
      determining PAH exposure. In invertebrates, the highest concentrations can be
      found in the internal organs, such as the hepatopancreas, and tissue
      concentrations appear to follow seasonal cycles, which may be related to
      variations in lipid content or spawning cycles. The major route of uptake for
      PAHs has been debated for years. For the more water-soluble PAHs, it is believed
      that the main route of uptake is through ventilated water and that the more
      hydrophobic compounds are taken in mainly through ingestion of food or sediment.
      There are many variables, such as chemical hydrophobicity, uptake efficiency,
      feeding rate, and ventilatory volume, which may affect the outcome. The route of
      uptake may be an important issue for short-term events; however, under long-term
      exposure and equilibrium conditions between water, prey, and sediment, the route
      of uptake may be immaterial because the same tissue burdens will be achieved
      regardless of uptake routes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7501869
TI  - Extinction of Vibrio cholerae in acidic substrata: contaminated fish marinated
      with lime juice (ceviche).
AB  - Millions of Vibrio cholerae O1 El Tor were rapidly eliminated when added to
      commercial ceviche prepared by marination of mahi-mahi fish in lime juice.
      Likewise, large masses of viable vibrios present in laboratory contaminated fish,
      were readily eliminated after immersion in lime juice, during the preparation of
      ceviche. The killing effect was evident within 5 min of exposure of vibrios to
      lime juice, with reductions of more than 99.9% of the initial bacterial mass.
      After 2 h of marination of fish with lime juice (the minimum recommended), no
      vibrios were detected in the lowest working dilutions (1:10, 1:100). The Vibrio
      mass eliminated by lime juice was 2 to 6 logarithms greater than the maximum
      infectious dose, and 4 to 8 logs greater than the minimum infectious dose to
      induce cholera El Tor. Also, the killing time was shorter than the elapsing time
      between preparing and serving food in homes or restaurants. The traditional
      marination of fish with lime juice or its addition to seafood and meals
      immediately before consumption, should be protected and promoted to prevent
      infection with cholera vibrios. In the face of an epidemic of cholera,
      consumption of ceviche prepared with lime juice would be one of the safest ways
      to avoid infection with V. cholerae.

PMID- 7501870
TI  - Extinction of Vibrio cholerae in acidic substrata: contaminated cabbage and
      lettuce treated with lime juice.
AB  - Lime juice killed millions of Vibrio cholerae O1, El Tor, Inaba, present on
      cabbage and lettuce contaminated in the laboratory. The lethal effect was evident
      within 5 min of exposure to lime juice. No vibrios could be recovered at dilution
      1:10 using alkaline peptone water (APW) and thiosulfate-citrate-bile salts
      saccharose agar (TCBS). More than 99.9% of the initial inoculum was effectively
      destroyed. The number of vibrios killed by lime juice was 2 to 6 logarithms
      greater than the maximum infecting dose, and 4 to 8 logs greater than the minimum
      infecting dose for cholera El Tor. The time interval needed for killing was
      smaller than the usual waiting time for serving food in homes and restaurants.
      The addition of lime juice to non-acidic foods, beverages and water, is strongly
      recommended to prevent infection with cholera vibrios and other acid-sensitive
      microorganisms. This measure is particularly important for rural and slum
      populations in the tropics and subtropics.

PMID- 7501871
TI  - Seasonal incidence and hemoparasite infection rates of Ixodid ticks (Acari:
      Ixodidae) detached from cattle in Costa Rica.
AB  - To determine the tick species hindering the cattle industry in Costa Rica and to
      assess infection rates of ticks with three important hemoparasite species, cattle
      were monitored during a period of six months (October 1992-March 1993). Four
      farms were located in the dry pacific region of the canton of Tilaran and a fifth
      farm on the slopes of the Poas volcano in a cool tropical cloud-forest ecosystem.
      On each farm 3 to 5 animals of 6 to 24 months of age were selected at random. All
      ticks were removed on a monthly basis from the right half side of each animal,
      while the site of attachment was recorded. Ticks were counted and differentiated
      according to species, developmental stage and sex. Moreover, engorged female
      ticks were assayed for the presence of Babesia bigemina, Babesia bovis and
      Anaplasma marginale using the polymerase chain reaction (PCR) multiplex system.
      Two species of ticks, Amblyomma cajennense and Boophilus microplus, were
      encountered on the cattle in the Tilaran region and one species, B. microplus,
      was detected in the Poas region. Two to ten times as many ticks were encountered
      in the Tilaran region than in the Poas region, which is in accordance with a
      stable enzootic protozoan disease situation in the former region and an unstable
      epizootic situation in the latter region. Nymphal and adult stages of both tick
      species were present in largest numbers on the ventral parts of the animals. PCR
      analysis of entire ticks indicated very high infection rates with hemoparasites
      of veterinary importance. This was in accordance with high seroprevalence rates
      in the hosts.

PMID- 7501872
TI  - [Phylogeny of lice (Insecta: Anoplura) of the Old World Monkey (Catarrhina)].
AB  - The genera Pediculus and Pthirus were studied cladistically, although the genus
      Pedicinus was also taken into account. Morphological characters from the
      literature, and some established through direct study were analyzed. Using five
      methods of cladistic analysis, one most parsimonious tree with a c.i. = 0.84 and
      a length of 38 was obtained ((Pedicinus)+(Paenipediculus+(Parapediculus+(Pedicu
      lus humanus capitis+Pediculus humanus humanus). A novelty of this study is the
      inclusion of the subgenus.

PMID- 7501873
TI  - [Food habits of the rainbow trout Oncorhynchus mykiss (Salmoniformes: Salmonidae)
      in an Andean creek of Venezuela].
AB  - Monthly stomach context samples of rainbow trout from Mucunutan stream (Merida,
      Venezuela), were collected from, March 1987 to February 1988 (n = 306). The major
      dietary components were Ephemeroptera, Trichoptera and Diptera. Baetodes sp. was
      the most important food item based on numerical composition (43%) and frequency
      of occurrence (88%). When the gravimetric method was used Leptonema sp. was the
      major dietary component. The diet was not a function of sex. The consumed fauna
      was more similar to the drift invertebrate fauna than to that of benthos (p <
      0.01). The fluctuations on the stomach content paralleled changes of food
      availability in the environment.

PMID- 7501874
TI  - Occurrence of the bacteria Listeria spp. in raw milk in Costa Rica.

PMID- 7501875
TI  - A trichloroethylene risk assessment using a Monte Carlo analysis of parameter
      uncertainty in conjunction with physiologically-based pharmacokinetic modeling.
AB  - A Monte Carlo simulation is incorporated into a risk assessment for
      trichloroethylene (TCE) using physiologically-based pharmacokinetic (PBPK)
      modeling coupled with the linearized multistage model to derive human
      carcinogenic risk extrapolations. The Monte Carlo technique incorporates
      physiological parameter variability to produce a statistically derived range of
      risk estimates which quantifies specific uncertainties associated with PBPK risk
      assessment approaches. Both inhalation and ingestion exposure routes are
      addressed. Simulated exposure scenarios were consistent with those used by the
      Environmental Protection Agency (EPA) in their TCE risk assessment. Mean values
      of physiological parameters were gathered from the literature for both mice
      (carcinogenic bioassay subjects) and for humans. Realistic physiological value
      distributions were assumed using existing data on variability. Mouse cancer
      bioassay data were correlated to total TCE metabolized and area-under-the-curve
      (blood concentration) trichloroacetic acid (TCA) as determined by a mouse PBPK
      model. These internal dose metrics were used in a linearized multistage model
      analysis to determine dose metric values corresponding to 10(-6) lifetime excess
      cancer risk. Using a human PBPK model, these metabolized doses were then
      extrapolated to equivalent human exposures (inhalation and ingestion). The Monte
      Carlo iterations with varying mouse and human physiological parameters produced a
      range of human exposure concentrations producing a 10(-6) risk.

PMID- 7501876
TI  - Characterizing perception of ecological risk.
AB  - Relatively little attention has been paid to the role of human perception and
      judgment in ecological risk management. This paper attempts to characterize
      perceived ecological risk, using the psychometric paradigm developed in the
      domain of human health risk perception. The research began by eliciting a set of
      scale characteristics and risk items (e.g., technologies, actions, events,
      beliefs) from focus group participants. Participants in the main study were 68
      university students who completed a survey instrument that elicited ratings for
      each of 65 items on 30 characteristic scales and one scale regarding general risk
      to natural environments. The results are presented in terms of mean responses
      over individuals for each scale and item combination. Factor analyses show that
      five factors characterize the judgment data. These have been termed: impact on
      species, human benefits, impact on humans, avoidability, and knowledge of
      impacts. The factor results correspond with initial expectations and provide a
      plausible characterization of judgments regarding ecological risk. Some
      comparisons of mean responses for selected individual items are also presented.

PMID- 7501877
TI  - [Radiographic and histologic observations of autoclaved and non autoclaved
      allografts in the distal femoral metaphysis in dogs].
AB  - PURPOSE OF THE STUDY: A canine experimental work was performed, to study
      osseointegration of cortico-cancellous bone allografts implanted in the lower
      femoral metaphysis. Particular attention was focused on observing the effects of
      autoclaving, used as a sterilizing method, on the osseointegration of bone
      allografts. MATERIAL AND METHODS: Eighteen dogs were operated on and three groups
      were formed according to the type of graft: the first group included 4 autoclaved
      autografts and one animal, in which no graft was implanted. The second group
      included 11 frozen allografts in which 4 had been autoclaved. The third group
      included 2 animals, who received autoclaved allografts and were sacrificed at 10
      months. In the first two groups, all animals were treated with the same protocol:
      graft stabilization using a plate, and specimen harvest at 4 months after
      surgery. In the third group, graft stabilization was obtained by press-fit only,
      and no plate was used. RESULTS: Overall roentgenographic results were
      satisfactory, suggesting graft fusion with the host. Histological results were
      inferior to roentgenographic results, and showed graft resorption, but only some
      signs of bone formation at the periphery of the graft. DISCUSSION:
      Roentgenographic results appeared optimistic, when compared to histological
      results. This suggests that roentgenographic results should not be considered as
      a reliable criteria for graft osseointegration. Despite favorable experimental
      conditions (cortico-cancellous graft implanted in the metaphyseal region, in a
      loaded segment of the skeleton, optimum graft stabilization using lateral
      plating), histological results were poor. New bone formation was observed at the
      periphery of the graft, but the major part of the graft remained fibrous. No
      difference was found between autoclaved and non autoclaved allografts in this
      small series. CONCLUSION: These preliminary results suggest that autoclaving does
      not impair osseointegration of frozen bone allografts, which anyway remains
      incomplete.

PMID- 7501878
TI  - [Cinematic in vivo analysis of the knee: a comparative study of 4 types of total
      knee prostheses].
AB  - PURPOSE OF THE STUDY: The goal of the study was to assess in vivo kinematics for
      four designs of knee prosthesis during level walking, stair climbing and non
      weight-bearing flexion-extension. PATIENT AND METHODS: 19 patients with
      unilateral total knee arthroplasty (TKA) were included [5 bicruciate sparing
      prosthesis (BI), 5 posterior cruciate sparing prosthesis with flat tibial
      polyethylene (PP), 5 posterior cruciate sparing prosthesis with congruent tibial
      polyethylene (PC), 4 postero stabilised (PS)]. These 19 patients had no
      prosthesis nor pathological situation in any other joint of the lower limbs. Each
      of these 19 prosthesis had an HSS score greater than 80 and no radiographic signs
      of loosening. Magnitudes of the knee rotations (flexion-extension axial rotation
      valgus-varus) were evaluated with a 6 degrees freedom of motion electromagnetic
      goniometer during level walking, stair climbing and non weight-bearing flexion
      extension. The magnitudes of the three rotations were recorded for the 19
      prosthetic knees and for the 19 controlateral non prosthetic knees of the
      patients. Reproducibility of the method was also evaluated on 12 healthy subjects
      by comparison of magnitudes observed during two different recordings. RESULTS:
      Reproducibility was excellent for magnitudes of flexion (r = 0.95/p = 0.0001) and
      axial rotation (r = 0.55/p = 0.002) but less satisfactory for valgus-varus
      movements (r = 0.46/p = 0.005). The magnitudes of the three rotations were
      inferior for TKA in comparison with healthy knees for any activities. By
      comparison of the 19 prosthetic and non prosthetic knees we recorded smaller
      magnitudes of axial rotation during swing phase for level and stair climbing and
      during non weight-bearing flexion extension movements. Between the four kind of
      prosthesis we observed: greater magnitudes of flexion for BI and PC prosthesis
      during stair climbing (p < 0.05) and greater magnitudes of flexion for BI PC and
      PS prosthesis during stair descending (p < 0.05). PC prosthesis instead of a
      congruent polyethylene tibial plateau had greater magnitudes of axial rotation
      than non constrained BI prosthesis during stair climbing (p = 0.009). In spite of
      a high femoro-tibial congruency we recorded axial rotation in PS prosthesis
      during each activities. DISCUSSION AND CONCLUSION: Our method evaluating in vivo
      knee kinematics was reproducible. These four knee prosthetic designs in spite of
      a good functional results were unable to reproduce magnitudes of movements
      recorded in healthy subjects. The small number of prosthesis included in the
      study prompt us to consider as no definitive the differences observed between the
      4 designs. Anyway the influence of design on kinematics should be considered as
      relative since we recorded axial rotation for all four cruciate substituting
      prostheses although they had high femoro-tibial congruency. Influence of femoro
      tibial congruency and cruciate ligament sparing could be assessed in vivo by
      means of this reproducible method on a larger population.

PMID- 7501879
TI  - [Experimental capsulo-ligamentar lesions of the knee during passive
      hyperextension. Biomechanical aspects. A lesional evaluation and consequences].
AB  - PURPOSE OF THE STUDY: Passive hyperextension is a rare mechanism of injury of
      knee ligaments in clinical practice. The lesions are often complex and no
      consensus exists about their sequence. Our purpose was to study the mechanical
      behavior and the anatomical lesions of the knee following passive hyperextension
      until rupture. MATERIAL AND METHODS: 12 pairs of fresh human cadaveric knees were
      tested after resection of soft tissue except for the ligaments and the Popliteus
      muscle. Some of them had specific ligaments sections (PCL or posterior capsule).
      We used a "four point bending" model at a constant rate (V = 3 10E-4 m/s) and
      measured failure torque and bending stiffness of the knee. Results were expressed
      as percent of the response of the normal contra lateral knee. RESULTS: A wide
      range of absolute data was noted and correlated to the age and bone quality. Bony
      avulsion was constant. The posterior capsule was the first structure injured at
      an average of 23 degrees of recurvatum, followed by the posterolateral ligament.
      The PCL was the ultimate structure to fail at its femoral attachment, preceding
      complete dislocation of the knee. No ruptures of the ACL and medial collateral
      ligament were noted. After section of the posterior capsule, the stiffness of the
      knee decreased 40 to 80 percent compared to the normal opposite knee, whereas the
      isolated section of the PCL had no significant effect. DISCUSSION: The method
      used in this study appears reliable. "The four point bending" is a reproducible
      model and the use of paired specimens allows a quantitative approach. The use of
      elderly specimens at a low strain rate in this experiment remains a questionable
      point. Passive hyperextension is characterized by automatic external rotation
      resulting in asymmetrical posterior lesions and tears of the PCL at its femoral
      attachment. On the contrary, active hyperextension of the knee can produce ACL
      injury by anterior translation of the tibia under the femur consecutive to
      Quadriceps femoris contraction. CONCLUSION: Our experimental model is an
      effective and reproducible method to create passive hyperextension of the knee.
      The first structure to fail is the posterior capsule followed by the
      posterolateral ligament. The PCL is the ultimate structure to fail and no ACL
      rupture has been noted before dislocation. CLINICAL RELEVANCE: if passive
      hyperextension mechanism is suspected, isolated posterior capsule lesion may
      occur and should be repaired. On the contrary, PCL tear should never be isolated
      and always associated with peripheral ligament injuries.

PMID- 7501880
TI  - [Value of the study of somatosensory evoked potentials during surgical correction
      of scoliosis associated with syringomyelia. Apropos of 4 cases].
AB  - PURPOSE OF THE STUDY: The presence of a syringomyelia cavity increases the rate
      of neurological complications on the course of surgical treatment of scoliosis.
      We have evaluated the results of monitoring of somatosensory evoked potentials
      (SEP) in these situations. MATERIAL AND METHODS: Four patients presenting a
      scoliosis associated with syringomyelia have been operated through a posterior
      approach with CD instrumentation. SEP monitoring was performed pre and
      intraoperatively. We studied the latency and the amplitude of P40. RESULTS:
      Preoperative SEP showed in all cases posterior spinal cord involvement (even
      without clinical manifestations). During monitoring, we noted in one case no
      variation. In one case a flattening of the response with normalisation within 5
      minutes. In two cases a persistent flattening with normalisation within 10 and 15
      minutes following modification of the instrumentation. In all cases,
      postoperative neurological status was identical to preoperative one. DISCUSSION:
      Preoperative SEP can make the diagnosis of posterior spinal cord involvement even
      when clinical status is normal. The extent of the preoperative SEP abnormalities
      may preclude the risk of intraoperative neurological complications.
      Intraoperative SEP can be performed with the same anesthetic protocol and the
      same technique used when operating idiopathic scoliosis. The results seem
      reliable. When alteration occur as for idiopathic scoliosis alteration of the
      amplitude appears earlier than alteration of the P40 latency. Restoration of
      normal responses appears later than in idiopathic scoliosis. CONCLUSION: SEP
      monitoring should diminish the risk for neurological complications in the course
      of surgical treatment of scoliosis associated with syringomyelia.

PMID- 7501881
TI  - [Multifascicular intramedullary nailing of the forearm].
AB  - PURPOSE OF THE STUDY: Purpose of the study was to present the advantages of
      intramedullary nailing of long bones for treatment of fractures of the forearm.
      These advantages are 1) preserving the fracture-hematoma and 2) non exposure of
      bone. This technique is based on the technique of bundle nailing developed by
      Hackethal (1959). MATERIAL AND METHODS: In a 16-year period we performed
      Hackethal bundle nailing in 94 patients with 159 fractures. Hackethal developed
      the nailing procedure named after him in 1959. The rationale of Hackethal nailing
      is based on elastic jamming, which can only be achieved by following four rules:
      jamming of the nails in the cortical window, jamming then in the waist of the
      medullary cavity, spreading the bundle of nails in the metaphysis and filling up
      the conus of the medullary cavity with short nails. We confined Hackethal nailing
      to closed and first-degree open fractures of the midshaft of the forearm. If
      closed reduction and nailing were impossible, we performed a plate fixation (AO).
      Second- or third-degree open fractures were treated with external fixators.
      RESULTS: In 62.8 per cent patients surgery was performed within the first 8 hours
      following admission. We used two or three nails passing the fracture and one
      short nail. Except for 1 case, in which a cast was necessary, we achieved
      rotational stability. On average, the nails were removed after 11.5 months. The
      healing and complication rates were assessed by follow-up examination of 77
      patients. The results were excellent and good in 75.3 per cent patients,
      satisfactory 14.3 per cent and poor in 10.4 per cent. Complications consisted of
      a 0.74 per cent infection rate (osteitis), 2.2 per cent non-union, 1.5 per cent
      with a synostosis, 0 per cent refracture and 2.2 per cent migration of nails,
      combined with tendon rupture. We have seen 1 case with metallosis. DISCUSSION:
      There are four important benefits of this treatment. First with this principle
      bone healing is achieved after 2.6 month, but with the plate fixation it lasts
      7.5 month. Second, the rate of non-union goes down from almost 6 per cent to 1.5
      per cent. Third, the postoperative infection rate is reduced (0.74 per cent) and
      fourth joint motion is preserved. Our bad results are mainly caused by the
      polytraumatic conditions of some patients. CONCLUSION: In conclusion with our
      confined spectrum of indications Hackenthal nailing is a low-risk method, which
      leads to rotational stability and early bone healing.

PMID- 7501882
TI  - [Compression of the ulnar nerve at the elbow. Results of a series of 51 medial
      epicondyle osteotomies associated with decompression].
AB  - PURPOSE OF THE STUDY: Despite many publications concerning the physiopathology
      and the treatment of Ulnar tunnel syndrome treatment remains controversial.
      MATERIAL AND METHODS: The authors reviewed 51 patients operated on for ulnar
      nerve entrapment at the elbow by neurolysis combined with medial epicondylectomy
      in case of luxation or subluxation of the nerve. Average was 39 years, 74 per
      cent being males, 53 per cent manual workers. According to Mc Gowan's
      classification, 39 per cent were grade I, 12 per cent grade IIA, 20 per cent
      grade IIB and 29 per cent grade III. RESULTS: Few postoperative complications
      occurred: one postoperative hematoma, 4 painful scars without neurinoma, and one
      case of an elbow extension lag of 15 degrees. With an average follow-up of 4.6
      years, 39 per cent of the patients were cured, 27 per cent improved, 31 per cent
      unchanged and none worsened. As in all others techniques, excellent results only
      occurred in grade I and IIA. DISCUSSION: Anatomical and physiopathological
      studies show that compression, friction and elongation are the 3 components of
      the ulnar tunnel syndrome. The different conservative and surgical treatments are
      analyzed, taking into account both advantages and drawbacks. The medial
      epicondylectomy with decompression allows a "mini transposition" of the nerve but
      keeps the vascularization and the nerve intact. Its simplicity and our results
      are confirmed by all other series analyzed in the literature.

PMID- 7501883
TI  - [Essential bone cysts in children. Value of systematic cystography. Apropos of a
      series of 42 cysts].
AB  - INTRODUCTION: The treatment of children's essential bone cysts, is controversial.
      Intra focal injection of a corticoid, the Methylprednisolone, described by
      Scaglietti in 1974, given in most of the case serials, a rate of healing of more
      than 30 per cent. MATERIAL AND METHODS: The case serial we present include 42
      essential bone cysts treated between 1975 and 1992 in the orthopaedic department
      of Necker Enfants Malades hospital. These children have been reviewed with a mean
      follow up of 4 years. A healing rate over 35 per cent has been noticed. However,
      some failures stayed completely an understanding even if nothing at the beginning
      let suppose a slower evolution. RESULTS: Attempting to explain those phenomenes,
      the authors realised in 70 per cent cases, an opaque cystography, before the
      Methylprednisolone injection. This simple radiological technique permitted to
      reveal abnormal aspect in 75 per cent cases. Most of the time, it shows massive
      veinous licks in an abnormal veinous system or one or plurial separations of the
      cystic area. This type of picture could perfectly explain the defect of the
      corticoids action by a lick of the solution or by a partial unefficacity of the
      solution because of the separation in the cyst area. The hypothetic idea has been
      completed by the calcul of the duration of the evolution. Effectively, the cysts
      showing an abnormal cystography had a longer healing delay compared to the cyst
      whose cystography was normal. CONCLUSION: The opaque cystography is for us a
      necessary element in the treatment of essential bones cysts, once the diagnostic
      is certain and the indication of intra focal corticoid injection has been
      retained. The radiographic study of the cyst area permits to precise the
      treatment; for example multiplying the injections in the areas of the cysts when
      there is separations and overseing the evolution.

PMID- 7501884
TI  - [Video-assisted anterior extra-peritoneal approach of the inferior lumbar spine].
AB  - PURPOSE OF THE STUDY: The aim of this study is to describe a new operative
      technique for anterior lumbar and lumbosacral fusion using a video assisted
      anterior extra peritoneal approach. MATERIAL: Ten patients were operated on.
      There were 3 men and 7 females. Age at operation ranged from 18 to 55. There were
      8 degenerative and 2 iatrogenic discopathias. Fused level was L4-L5 (5 patients)
      and L5-S1 (5 patients). Average hospital stay was 6 days. METHODS: A small
      vertical 4-5 cm incision is made on the mid line, centered on the umbilicus for
      the approach to L4-L5, and between the umbilicus and pubis for the L5-S1
      approach. The peritoneum is cleaved from the abdominal wall on the left side, and
      the anterior aspect of the spine is progressively freed. The endoscope is
      laterally introduced. It gives an excellent view of the prevertebral area. A
      specially designed retractor is used for retraction of the iliac vessels.
      Following removal of the intervertebral disc, a special spreader allows obtention
      of a normal intervertebral space height and insertion of an autogenous iliac
      graft. DISCUSSION: Anterior approach of the lumber intervertebral discs allows
      disc resection and grafting in a strict middle position. The extra peritoneal
      simplifies the postoperative course and avoids digestive and septic complications
      of the transperitoneal approach. The video assistance gives excellent exposure by
      a small incision with direct visual control; it should be differentiated form the
      true endoscopic lumbar surgery which is performed under C02 insufflation, with
      exclusive endoscopic vision and with instruments introduced through trocards.
      CONCLUSION: Video-assistance allows an approach to the lumbar and lumbosacral
      spine by an anterior non invasive extra peritoneal approach, with low morbidity,
      increasing the possibilities of anterior fusion in the treatment of lumbar
      discopathias and instability without radicular compromise.

PMID- 7501885
TI  - [Judet's acrylic prosthesis 42 years following implantation].
AB  - One case of Judet's acrylic arthroplasty surviving 42 years before revision is
      discussed. The literature pertaining to Judet's prosthesis is reviewed and
      reaction in bone to the prosthesis discussed as well as the porosity of methyl
      methacrylate.

PMID- 7501886
TI  - [Epidemiology of risks related to the environment].

PMID- 7501887
TI  - [Epidemiologic research on the environment and health: some methodologic
      aspects].
AB  - Research in environmental epidemiology deals with physical, chemical and
      biological agents whose presence--or relative absence--within the different media
      coming into contract with human beings (air, water, soil, food, etc...) may be
      harmful to human health. Some "major" environmental risk factors are well known.
      In a number of situations, however, environment-disease associations are "weak".
      This does not rule out the possibility that the exposures involved have a
      significant impact on human health, considering their prevalence which is
      frequently high. However, this complicates their study owing to the potential
      importance of biases as well as that of sampling fluctuations. Although
      increasing study size is of crucial importance, it is not sufficient to establish
      a clearcut distinction between "weak" associations and "diluted" ones. To improve
      our knowledge of health risks which are associated with environmental exposures,
      the basic methodological principles of epidemiological research--to define and
      adequately measure exposures, health outcomes, confounders and effect modifiers-
      may be very valuable to approach the study of "weak" associations: 1) identifying
      and quantifying the presence of the agents of interest in the environment,
      studying the distribution of environmental exposures among individuals and its
      determinants, taking into account the whole history of personal exposures and
      integrating adequately the short term time variability of exposures, giving
      special attention to the type and intensity of exposures may help in the
      definition and measurement of exposures; 2) carefully analyzing the interactions
      which may exist between the physical, chemical and biological agents of interest
      and the human body may greatly help in the elaboration, measurement and
      validation of relevant health outcomes (exposures to the target organs, early
      lesions and health impairments); 3) this same approach may also greatly
      contribute to the identification of constitutional or acquired individual
      characteristics which may interact with environmental agents in the development
      of diseases. While there is no guarantee that such approaches will successfully
      discriminate between "weak" and "diluted" associations, it is likely that
      inconclusive epidemiological evidence will be very difficult to avoid if such
      approaches are neglected by environmental epidemiologists.

PMID- 7501888
TI  - [Public health surveillance and the environment].
AB  - Since the 1970's, in many industrial countries, the awareness of environmental
      health risks has led to set up information systems in order to assess and monitor
      concentrations of pollutants in air, water or food. These monitoring systems aim
      to answer the question: "is the environmental contamination too high?". With this
      objective, concentrations of pollutants are compared to standards. Up to now,
      this approach has been favoured and many environmental data have been collected
      at a local, regional, national or international level. Nevertheless, other
      approaches are possible as the health surveillance which aims to directly monitor
      the effects of contaminants on health. More recently, a third approach has been
      developed which consists in linking environmental monitoring data and health
      monitoring data. These approaches are not exclusive. All of them aim to produce
      useful information to help decision-makers in the management of environmental
      issues. However, the question is "what are the conditions to be achieved for
      routinely collected data to fulfil the requirements of a real Public Health
      surveillance system?". The conditions, advantages and limits of these three
      approaches are discussed.

PMID- 7501889
TI  - [Principles of evaluation of public health risk for environmental exposures].
AB  - Assessing environmental health risk is fraught with difficulties: often, the
      agents under study are weak pathogens, and exposures are poorly characterised.
      Direct studies in man are frequently inconclusive (or inconsistent) because of
      the limited sensitivity of epidemiological studies. Experimental studies raise
      questions about the validity of animal to man extrapolation. However, taking
      steps to protect public health is needed and impose the use of all available
      data. Remaining uncertainties lead the health risk assessor to make assumptions.
      Such a process implies as much transparency as possible, both for ethical reasons
      and to allow the public to be involved in the debate. A formalized approach has
      been proposed by various US agencies in charge of public health. One important
      matter is a strict separation between risk assessment and risk management. The
      procedure is divided into four portions: hazard assessment, exposure assessment,
      dose-response assessment which includes the study of risk at low doses--sometimes
      through the use of mathematical high to low dose extrapolation modelling--and
      risk characterisation.

PMID- 7501890
TI  - [Longitudinal study of radiologic anomalies in subjects working in asbestos
      insulated buildings].
AB  - The respiratory effects of environmental pollution by asbestos was examined in a
      cohort of subjects working inside university buildings partly insulated with
      asbestos containing materials (University of Jussieu in Paris). The present study
      concerned 727 subjects having undergone two standard radiographic examinations
      (postero-anterior and oblique chest x-ray) in the period 1981-1992. The first
      examination was realized between 01/01/81 and 31/12/85 and the second examination
      took place between 01/01/86 and 31/12/92. The subjects were classified into three
      groups according to their exposure status: the group G1 consisted of 161 workers
      occupationally exposed to asbestos; the group G2 comprised 416 subjects working
      for at least 15 yr in asbestos-insulated buildings without known occupational
      exposure to asbestos; the group G3 consisted of 150 workers working for at least
      15 yr in the university with no known exposure to asbestos. Whatever the
      radiological abnormalities considered, no significant difference was observed
      between G2 and G3 in cross-sectional analyses of the two phases. The group G1
      exhibited a significantly higher prevalence of pleural thickening compared to the
      other exposure groups after adjustment for confounding variables. Detailed
      examination of oblique x-ray allowed to confirm that pleural thickening were
      largely due to extrapleural fat. Concerning the changes in pleural abnormalities
      between the two phases of the study, no difference was observed between G2 and
      G3. This study was unable to show any excess of radiographic chest abnormalities
      among subjects working in asbestos-insulated buildings compared to non-exposed
      subjects. However, the participation in the second phase of examination was
      51.2%. The study is still on-going. Therefore, it would be necessary to continue
      to follow-up the subjects because respiratory disorders could occur after a long
      latent period.

PMID- 7501891
TI  - [Potential role of environmental and domestic exposure to tremolite in pleural
      cancer in New Caledonia].
AB  - A previous study of respiratory cancers in New Caledonia (1978-1987) showed an
      excess risk of pleural cancer in this South Pacific French Territory, leading to
      the identification of an environmental pollution. In some villages, the residents
      use for their houses a whitewash made from a rock derived from local
      outcroppings. Analysis of samples of rock and whitewash showed that they
      consisted of tremolite asbestos. High levels of tremolite were detected in
      airborne samples collected in these villages and in biological specimens of
      patients with pulmonary cancer or mesothelioma; the concentrations of fibers are
      up to 78,000 fibers per litre of air and 44 millions of fibers per gramme of dry
      tissue. Besides the whitewash, the environmental exposure to tremolite fibers
      could also be associated with certain occupations. A case control study under
      process will allow the estimation of respiratory cancer risks associated with the
      exposure to tremolite.

PMID- 7501892
TI  - [Radon and cancer risk: epidemiological studies after occupational or domestic
      exposure].
AB  - The evaluation of cancer risk after exposure to radon is mainly based on the
      results of uranium miners follow-up. A cohort study on the French uranium miners
      has demonstrated an excess of lung cancer and of larynx cancer mortality. A
      linear dose-response relationship has been described between the excess relative
      risk of lung cancer and the cumulative exposure to radon (poisson regression).
      This study has contributed to a joint analysis of 11 cohorts of miners, the aim
      being a more precise evaluation of the different factors able to influence the
      dose-response relationship between radon and lung cancer mortality. These factors
      are: age at first exposure, attained age, time since exposure, the pattern of
      exposure over time and tobacco consumption. The extrapolation of the risk for the
      general public from the risk estimated after occupational exposure, has to be
      considered by taking in account several remarks: uranium miners are exposed,
      beside radon, to two other radiological components, gamma rays and long lived
      uranium dust, and to other substances specific of the mines, which are absent in
      the domestic environment but may with radon have an effect on the lung cancer
      risk. It was impossible to estimate directly, from these uranium miners data, the
      risk linked to radon for non-smokers and for female population. A case control
      study is currently be carrying out in the French hospitals, in order to estimate
      the risk of lung cancer linked to the last 30 years of radon exposure in the
      dwellings.

PMID- 7501893
TI  - [Study of demographic, environmental and congenital factors in the development of
      nevi in children between three and fifteen years old. Early results].
AB  - A survey of benign melanocytic naevi was conducted among school children in
      Montpellier (France) in 1993 with the aim to assess the evolution with age of the
      number of naevi and the factors influencing their number. Children in different
      age groups (3, 6, 9, 12 and 15 years) attending randomly selected public schools
      where included in the study. Dermatologists examined 651 children and recorded
      the number of naevi of more than 2 mm of diameter. Analysis was restricted to 565
      children whose parents responded to a historical questionnaire of exposure and
      sociodemographic data. Among these children the number of naevi per unit of area
      increased progressively with age although the number of naevi per unit of skin
      area reached a plateau at about 11 years of age for the girls and around 15 years
      of age for the boys. Puberty is a regulative factor for the number of naevi and
      the number of naevi per unit of area. Children whose parents were born in Europe
      were most likely to have naevi. Susceptibility to burns were also associated with
      few number of naevi and number of naevi per unit of skin area. The cumulative
      exposure to sun since birth and the cumulative exposure during the holidays
      increased the number of naevi and the number of naevi per unit of area but these
      variables are the last introduced into the logistic model. A prospective
      questionnaire can be used to assess the exposures and protection variables
      allowing a better estimation of the skin reaction to sun.

PMID- 7501894
TI  - [Prevalence of immediate allergy to respiratory allergens in fodder farmers in
      Doubs].
AB  - The Doubs is a damp, semi-mountainous fodder farming department in which
      occupational respiratory diseases (including asthma) are common in farmers. We
      studied the prevalence of IgE-mediated allergy (total IgE, Phadiatop and skin
      prick tests) in a group of 265 exclusive dairy farmers of both sexes of the
      department and in a control group of non exposed, administrative workers living
      in the same area. Skin prick tests were: Dermatophagoides pteronyssinus, Acarus
      siro, cat hair, cow danders, grass pollens, betullacea pollens (trees from the
      East of France), and hay extracts from the Doubs. Total IgE were higher than 180
      KUI/l in 26 (9.9%) farmers and in 15 (10.5%) controls (NS). Phadiatop was
      positive in 41 (15.7%) farmers and in 27 (19%) controls (NS). Prevalence of
      positive skin prick tests (at least one) in farmers and controls was respectively
      36% and 40% (NS). Farmers were more frequently sensitized to hay extracts (OR =
      1.7), cow danders (OR = 1.3) and less frequently to cat hair (OR = 0.63) than
      controls but the differences were not statistically significant. In conclusion,
      this study fails to give evidence of a risk of IgE-mediated allergy to work
      related and other common inhalation allergens in dairy farmers the Doubs.

PMID- 7501895
TI  - [Screening for lead poisoning in children by measuring lead levels in housing: a
      study of the Paris region].
AB  - Screening programs for lead poisoning in France rely usually on the preliminary
      identification of risk factors among children seen in Maternal and Child Health
      (MCH) clinics. To assess the potential relevance of screening strategies based on
      the quantification of exposure to lead in housing, we estimated first the
      prevalence of exposure to lead in a representative sample of older buildings,
      then the prevalence of lead poisoning among children living in those buildings
      where high levels of lead had been found. Exposure to lead was measured in dust
      and paint samples collected in hallways and other collective areas of the
      buildings. Venous blood samples were collected from the children aged 10 months
      to 6 years residing in buildings where lead exceeded 1.5 g/kg in paint samples or
      1000 micrograms/m2 in dust samples. Paint and dust samples were collected in 137
      buildings: 74% presented high dust and/or paint lead contents. Blood samples were
      collected from 145 out of a total of 189 children residing in these buildings:
      blood lead levels (PbB) were higher than or equal to 10 micrograms/dl for 65% of
      these children; 29% were higher than or equal to 15 micrograms/dl, 16% higher
      than or equal to 20 micrograms/dl. Out of 42 children with PbB > or = 15
      micrograms/dl, 21 had not been previously identified through the screening
      program conducted in local MCH clinics. Clinic-based and environment-based
      screening appeared to be complementary. It seems thus justified to develop
      screening strategies based on the assessment of exposure to lead in the
      environment.

PMID- 7501896
TI  - [Evaluation of decontamination interventions in 59 homes of children with lead
      poisoning].
AB  - Old peeling paint with high content of lead has been identified as the main
      source of lead poisoning for children screened in Paris since 1985. In 1989,
      Medecins Sans Frontieres and Migration Sante tested abatement methods in 59 homes
      of severely lead-poisoned children. The effectiveness of abatement is evaluated
      with respect to the evolution in dust lead contents and of the children's blood
      lead levels. Lead content wsas measured in dust samples collected from the floor
      of the homes before abatement, then every three months after abatement; results
      are available for 24 homes. Blood lead levels were assessed in the course of the
      children's medical follow-up; results are available before and after abatement
      for 78 children living in 41 of the abated homes. The effect of abatement on the
      children's blood lead level was assessed through multivariate analysis. The
      median decrease in dust lead contents was 365 micrograms/m2 one to two months
      after abatement and 300 micrograms/m2 three to six months after abatement.
      However, dust lead contents of more than 1,000 micrograms/m2 were found in more
      than half of the communal areas of the buildings six to twenty-eight months after
      abatement. For 2 of the families, abatement was associated with an increase in
      the children's blood lead-levels. For all of the other children, abatement was
      associated with a significant decrease in blood lead levels, controlling for the
      child's age and initial lead poisoning level, and for the overall downward trend
      in blood lead levels over time since the initial screening.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7501897
TI  - [Early markers of nephrotoxicity: variation factors and reproducibility].
AB  - Epidemiological validity of early markers of nephrotoxicity currently used in
      occupational epidemiology has been poorly investigated. The aim of this study was
      to identify variation factors of these markers, to quantify their intra- and
      inter-individual variability and to evaluate the consequences of these results on
      study size and power. A cross-sectional survey was carried out in 1991 in a
      rotogravure plant including 168 male subjects (92 exposed to toluene and 76
      controls). Blood and urine samples were taken twice: at study onset and one to
      five months later for 40% of the subjects. Creatinine and beta-2-microglobulin
      (beta 2M) were measured in both blood and urine; microalbumin (microALB), N
      acetyl-beta-D-glucosaminidase (NAG), and alanine-aminopeptidase (AAP), in urine.
      Sources of physiological variation were reduced by standardization of collection
      and assay methods. Subjects completed a questionnaire to record information about
      their personal characteristics, alcohol, tobacco and drug consumption and their
      health. Statistical analysis of all subjects was adjusted for exposure status.
      Several factors were significantly related to the markers: age with beta 2M, NAG
      and AAP; smoking, alcohol drinking, and blood pressure with both microALB and
      NAG; urinary pH with beta 2M. These factors explained from 13 to 21% of the total
      variance of these markers. Short-term reproducibility, i.e. the correlation
      between the two measurements, was high for microALB (r = 0.75), moderate for NAG
      (r = 0.51), and low for beta 2M (r = 0.33) and AAP (r = 0.17). These results
      showed that confusion bias in the evaluation of exposure-marker association can
      be reduced by adjusting for several factors and that accuracy and study power can
      be improved by repeating measurements, especially for beta 2M and AAP.

PMID- 7501898
TI  - [Urinary excretion of fluorides in children living around an aluminum smelter].
AB  - Aluminium industry discharges fluoride into the atmosphere and several studies
      have shown a slight but significant contribution to the intake of fluoride by
      children living around aluminium smelters. A monitoring system was set up in
      1991, just before a new aluminium smelter came into operation in Loon-Plage, on
      the North Sea coast, to study the evolution of the urinary fluoride excretion in
      children around the plant. Every year, 250 children under 14 are sampled in
      infant clinics, nursery schools and a secondary school. Urinary fluoride
      excretion was assessed by a potentiometric method on a spot morning urine sample
      and information on exposure factors was obtained by questionnaire. Urinary
      fluoride levels decreased with age (r = 0.31) and were higher in children
      drinking a local bottled water rich in fluoride (geometric mean in mg per gram of
      creatinine: 0.69 vs 0.52) or taking fluoride tablets (0.82 vs 0.52). The mean
      urinary fluoride excretion in children did not vary significantly between 1991
      (geometric mean: 0.70 mg per gram of creatinine, 95% CI: [0.64-0.77]), 1992 (0.68
      [0.62-0.75]) and 1993 (0.68 [0.61-0.76]), even after adjustment for potential
      confounding factors and despite a moderate increase in atmospheric fluoride
      levels.

PMID- 7501899
TI  - ["I have read about the dinosaur". How does the Italian physician keep up with
      the times?].

PMID- 7501900
TI  - [Long-term study of anti-HCV reactivity using 3d generation recombinant
      immunoblot assay in acute post-transfusion hepatitis].
AB  - Twenty-five patients with post-transfusional C hepatitis have been tested
      retrospectively by IIIrd generation Recombinant Immuno Blot Assay (RIBA) in order
      to evaluate long-term anti HCV antibodies dynamics. The test was performed 1, 15,
      70 and 140 days after the onset of the disease. Fifteen patients recovered and 10
      became chronic. In the 15th day anti C33 and anti C22 were found in 76% of
      subjects, anti NS5 in 68% and anti C100 in 32%. In the 70th day, 96%, of patients
      had anti C22, 92% had anti C33 and anti NS5 and 52% showed anti C100. In the
      140th day, all patients were positive for anti C33, and C22 and anti NS5, while
      anti C100 was present in 64%. Five-six years after the acute disease, all
      chronically progressed patients had a complete antibody pattern by RIBA III,
      while anti C22 was the only positive persisting antibody, among the recovered
      patients. Anti C22, anti C33 and anti NS5 shorten the serological "window-phase"
      during acute hepatitis, but no further improvement in diagnostic precocity seems
      to be guaranteed by third generation RIBA. The precocious appearance of complete
      RIBA III pattern during acute hepatitis may represent a herald for a chronic
      evolution of the disease.

PMID- 7501901
TI  - [Influence of Helicobacter pylori on gastric secretion. Study on variously
      associated gastric body, fundus and antrum chronic gastritis].
AB  - Among the various themes related to Helicobacter pylori (HP) which is still a
      subject of discussion, there is the possible influence of this bacterium on
      gastric secretory physiology. In the present study, an evaluation has been
      carried out of stimulated gastrinemia, stimulated acid secretion and total peptic
      activity in gastric juice in the course of a paradigmatic condition, as
      autonomous chronic gastritis, in order to reveal possible modifications induced
      by the HP infection. In cases of HP positive chronic superficial antral gastritis
      associated either with normal body-fundic mucosa or with superficial gastritis,
      there is a significant increase of stimulated gastrinemia in comparison to HP
      negative groups and controls. In the course of body-fundic atrophic and
      preatrophic chronic gastritis associated either with antral superficial chronic
      gastritis or with antral atrophic gastritis, there are no statistically
      significant differences between HP positive and HP negative subjects. As regards
      acid and pepsin secretion no significant differences emerge in any group between
      HP positive and HP negative subjects. In the HP positive subjects with antral
      superficial gastritis and higher gastrin values the study of acid and pepsin
      secretion has yielded no significant variations. From the results of this study
      it emerges how gastric secretory parameters vary exclusively according to the
      histologic state of gastric mucosa. Therefore, the lesion action of HP may mainly
      be attributed to a direct action, rather than to substantial gastric secretory
      changes.

PMID- 7501902
TI  - [Eosinophilic pustular folliculitis and Ofuji disease. A case report].
AB  - We describe the case of a young man of Calabrian origin, who came to our
      observation for the appearance of erythematous pustular, intensely itching,
      lesions on the arms, trunk and, in a less extent, on the face. The blood count
      revealed a differential cell count of 16.8% eosinophils. Serum IgE levels were
      elevated (1000 IU/ml), and T cell subsets showed an increase in CD8+ and a
      decrease in CD4+ with an inversion of CD4+/CD8+ ratio (= 0.78). The result of the
      following investigations were either normal or negative: anti-(ds)DNA antibody,
      anti-nuclear antibody, anti-smooth muscle antibody, anti-striated muscle
      antibody, serological tests for viral, bacterial, fungal and parasitic diseases
      and cultural examination of the material from lesion. Histopathological
      examination of a biopsy specimen from the left arm showed the presence of
      abundant perivascular inflammatory infiltrate in the dermis and inflammatory
      infiltrate, with numerous eosinophils, around sebaceous glands. Taken together,
      all these data suggest the diagnosis of eosinophilic pustular folliculitis, a
      dermatosis of unknown etiology, with a histopathological picture identical to
      Ofuji's disease. Eosinophilic pustular folliculitis can be associated with HIV
      infection or haematological diseases (as non-Hodgkin lymphomas, myeloma, etc.);
      it was also reported in adult immunocompetent healthy individuals and in
      children. On the basis of our findings, we propose that this case should be
      classified as an idiopathic form, as we were not able to demonstrate any
      associated disease.

PMID- 7501903
TI  - Hyperleukocytosis with marked hypereosinophilia. Morphologic and cytochemical
      pathologic aspects of eosinophils. Eosinophilic leukaemia?
AB  - Excluding the most frequent pathologies that cause hypereosinophilia, we report a
      case of a patient with hyperleukocytosis and marked hypereosinophilia that showed
      morphological abnormalities in conjunction with cytochemical pathologic aspects.
      Physical examination, laboratory results and cytochemical abnormalities induced
      us, although a normal karyotype, to consider the possibility of eosinophilic
      leukaemia.

PMID- 7501904
TI  - Use of furazolidone for the treatment of microsporidiosis due to Enterocytozoon
      bieneusi in patients with AIDS.
AB  - The efficacy of furazolidone for treatment of intestinal microsporidiosis due to
      Enterocytozoon bieneusi was studied in three patients with AIDS. All patients had
      chronic diarrhoea and weight loss. Mean CD4 cell count was 34.6/mm3. A course of
      furazolidone (100 mg orally four times a day) was given for 20 days. The drug was
      well tolerated and neither side effects nor alterations in the laboratory
      parameters were noted. Diarrhoea ceased within a mean of 12 days of starting
      treatment and clearance of microsporidian shedding in stool was observed. In one
      of the patients, however, symptomatic microsporidiosis recurred. Therefore
      furazolidone seems to have a transient but significant effect on intestinal
      infection due to Enterocytozoon bieneusi.

PMID- 7501905
TI  - Serum antibody detected by fluorescent antibody test in patients with symptomatic
      Blastocystis hominis infection.

PMID- 7501906
TI  - [Quality of life in medicine. Introduction of the concept in clinical
      epidemiological research and health care planning].
AB  - The article summarizes current issues and future directions in Quality-of-Life
      (QoL) investigation. The concept of QoL aims to provide an accurate evaluation of
      how a disease and its related treatments impact upon patient's physical,
      psychological and social well-being. Moreover, QoL indices have been employed as
      an outcome variable in randomized controlled trials and in the economic analysis
      of treatments. Though researchers are still debating what should be included in
      QoL assessment and how investigations should be carried out, relevant
      contributions were provided, particularly in the fields of oncology and
      cardiovascular diseases. The need of meaningful data on patient's QoL calls upon
      a more rigorous methodological framework and the availability of psychometrically
      sound questionnaires that are appropriate to the population, setting, and goals
      of investigation.

PMID- 7501907
TI  - [Internet and medicine].
AB  - The World Wide Web creates world-circling medical information bridges connecting
      all the world. Web sites maintained by universities and institutes are prime
      sources for hard scientific data about medical research. These sites are more and
      more informative and usually readable. For some commentators the Web is the
      greatest advance in information transfer since the invention of the printing
      press. Some people believe that electronic medical publishing will fundamentally
      change the way that science gets done. However, an explicit policy is needed for
      the medical sites on the Internet because of its enormous capacity to transmit
      information.

PMID- 7501908
TI  - [Communication of bad information: general indications and guidelines].
AB  - Breaking bad news to a patient requires from the physician specific communication
      skills and interpersonal abilities which, in the past, traditional medical
      curricula have tended to neglect. The authors present in this paper general
      guidelines for breaking bad news, illustrating how to structure the interview and
      how to evaluate patients' need for information before the communication of the
      diagnosis. A first step comprised the evaluation of how the patient perceives and
      interprets his illness and what type of information he wants to receive. The
      physician should establish the patient's actual knowledge of his illness which
      must be the starting point for the successive communication of the diagnosis. To
      facilitate patient's understanding of the news, the physician has to consider his
      perception of the illness, and to taylor the information he wants to convey
      accordingly. Patients' knowledge will be integrated gradually until the desired
      level of completeness is reached. It has to be considered that patients' need for
      information may change during the course of illness. Information giving is
      therefore part of a process. Physicians should be alert to possible changes and
      adjust the quantity and quality of information they give according to the
      changing needs of their patients.

PMID- 7501909
TI  - [Pharyngo-tonsillitis: Current clinical, bacteriological, serological and
      therapeutic aspects].
AB  - The authors present the pharyngo-tonsillitis in four fields: clinical,
      bacteriology, serology and treatment. They insist on the danger of the beta
      hemolytic Strep A, the failures of the ASLO detection and stress the execution of
      the rapid antigenic test at the office. They suggest the limitation of the
      administration of antibiotics and the prescription of a penicillin which is much
      better than macrolides or cephalosporins of second or third generation.

PMID- 7501910
TI  - [Snake bites].
AB  - Snake bites are a rare occurrence in Belgium. Nevertheless, all doctors should
      know how to react to this potentially very dangerous emergency. A snakebite does
      not necessarily result in poisoning: the effects can range from a little local
      discomfort to a severe systemic reaction with multiple organ failure. Therefore,
      all snake bites must be treated as serious and should receive adequate treatment.
      At the same time, hysterical over reaction must be avoided for this risks
      complications. This article reviews the principal elements of snake bite
      treatment: from the emergency stage through to stabilization in the hospital. Key
      points raised are the necessity to immobilize the affected region, to establish
      adequate perfusion and to anticipate infectious complications. Serum therapy
      indications are reviewed together with adjuvant interventions such as
      corticotherapy and heparin therapy.

PMID- 7501911
TI  - [Update on ovarian hyperstimulation syndrome].
AB  - The ovarian hyperstimulation syndrome (OHSS) is the most important complication
      of the pharmacological ovulation induction. Exclusively postovulatory, it is
      clinically characterized by a massive ovarian enlargement associated with an
      acute third-space fluid shift responsible for the development of ascites, and
      sometimes pleural and/or pericardial effusion. While mild OHSS has no
      consequence, severe forms can be life-threatening because of associated
      hemodynamic troubles. The main risk factors are the polycystic ovarian syndrome
      and an explosive ovarian response to the stimulation characterized by high serum
      oestradiol levels and an increased number of follicles. Ultrasound and endocrine
      monitoring make prevention measures possible, mainly by either abandoning the
      stimulation cycle or, during in vitro fertilization, cryopreserving the embryos
      for subsequent replacement in another cycle. Treatment consists in correcting
      circulatory and electrolyte imbalance. Paracentesis is more and more
      systematically proposed in the severe forms.

PMID- 7501912
TI  - [Thyroid and AIDS].
AB  - Two types of thyroid biochemical abnormalities (TBA) are observed in AIDS. The
      unspecific TBA are similar to TBA reported in the Euthyroid Sick Syndrome. An
      increased serum TBG of unknown origin and a decreased circulating rT3 are the
      most specific TBA of AIDS. The latter abnormality may be in relation with an
      elevated level of TNF. The frequency of serum antithyroid antibodies seems higher
      than in control groups. Opportunistic infections of the thyroid gland or
      destruction of the thyroid by Kaposi's sarcoma are also reported in AIDS.

PMID- 7501913
TI  - [Rickets resistant to calcitropic hormones].
AB  - Resistance to vitamin D is known since a long time but was erroneously ascribed
      to phosphate deficiency (phosphate diabetes or deficiency in tubular phosphate
      reabsorption). True vitamin D resistance can either be due to lack of the
      receptor itself or to structural abnormality in the hormone -or DNA-binding site
      of the receptor whereas in a few cases post-receptor resistance has been
      documented. In view of the therapeutic consequences, diagnosis of vitamin D
      resistance is needed in every case of rickets not due to simple vitamin D
      deficiency. Such cases can be easily recognized by normal 25-hydroxyvitamin D
      concentration in the presence of biochemical, radiological or/and histological
      signs of rickets.

PMID- 7501914
TI  - [Comparison of 2 techniques for measuring lymphocyte proliferation: tritiated
      methyl-thymidine incorporation and propidium iodide fluorometry].
AB  - In vitro lymphocyte mitogenic stimulation by phytohemagglutinin A was determined
      in 20 subjects, comparing tritiated thymidine incorporation and nuclear propidium
      iodide fluorescence. Unexpectedly, no correlation could be found between the two
      measures. The pitfalls of both methods are reviewed and discussed. The inability
      to validate one test by the other restricts the interpretation of the results
      obtained with one method and prevents their generalization. Without another gold
      standard at the present time, specific and limited method-dependent norms should
      be defined.

PMID- 7501915
TI  - [Novel autograft method using positive selection of CD34 stem cells].
AB  - High dose chemotherapy with autologous blood stem cell rescue becomes widely used
      for patients with hematologic malignancies and solid tumors. Recently, it has
      been demonstrated that stem cells characterized by the CD34 antigenic marker
      could be positively selected using an anti CD34 monoclonal antibody and an avidin
      biotin immunoabsorption device. We report our experience of twelve selections and
      ten grafts. A CD34+ cells enrichment of 1.9 log (purity: 72%) and a CFU-GM cells
      concentration of 1.6 log have been obtained. In ten transplanted patients, the
      hematological recovery was similar to that obtained with non selected blood stem
      cells. The CD34+ cells purification allows mini graft infusion and purge of
      residual tumor cells implicated in relapse after autologous stem cells
      transplantation.

PMID- 7501916
TI  - [What is your diagnosis? Left ventricular hypertrophy].

PMID- 7501917
TI  - [Surgery of colorectal carcinoma].
AB  - Surgery is the primary mode of therapy for colonic and rectal cancer. The
      principles of surgery are: laparotomy for staging, wide en bloc resection of the
      primary tumor and lymphadenectomy for staging as well as possible therapeutic
      benefit. Reasonable efforts should be made intraoperatively to prevent
      intraluminal and intraperitoneal spread. Resection of metastases can prolong
      survival in stage D patients confined to the liver. Dukes C colon cancer patients
      should receive multiagent chemotherapy. There is no well defined role for
      radiation therapy as adjuvant treatment in colon cancer. Local failure pattern
      and treatment strategies are different for cancer of the rectum. Surgery remains
      the mainstay of treatment for all lesions; other modalities are adjunctive.
      Lesions within 5 cm of the anal verge usually require abdominoperineal resection,
      while the other are treated with a low anterior resection. New techniques are
      emerging to preserve the anal sphincter and gastrointestinal continuity, and
      these are being tested to determine if adequate tumor control is obtained.

PMID- 7501919
TI  - [Adjuvant radiochemotherapy of rectal carcinoma].
AB  - Adequate surgical treatment is the basis for any adjuvant therapy. However, even
      in case of optimal surgery local recurrence rates of 20 to 30% are to be expected
      for stage II/III patients with 5-year-survival figures in the range of 40 to 60%.
      In some series, e.g. the results of the Surgical Department of the University of
      Erlangen, a significant correlation between local control and survival does
      exist. Postoperative radio-therapy decreases the risk of local recurrence but has
      -as postoperative chemotherapy--only marginal impact on survival. Combined
      adjuvant treatment (radio-therapy plus 5-FU-chemotherapy) has significantly
      increased the 5-year survival figures by 10 to 15% in two randomized trials and
      is considered as standard adjuvant treatment. From a radio-oncological point of
      view, most studies may be criticized at least in part because of low preoperative
      doses, inadequate technique without individual treatment planning and shielding,
      unfavourable fractionation, or dose reductions of radiotherapy in case of
      chemotherapy. Further improvement of local efficacy of radiotherapy and reduction
      of therapy-related toxicity seems, therefore, possible. Innovative approaches in
      radiation oncology mainly include preoperative strategies.

PMID- 7501918
TI  - [Adjuvant treatment of colonic carcinoma].
AB  - After many years of negative trials of adjuvant chemotherapy in colon cancer, two
      studies in the years 1989 and 1990 of the NCCTG and the Intergroup Trial,
      respectively showed a significant reduction of relapse and improved survival in
      patients treated with 5-FU and levamisole in an adjuvant setting. The absolute
      and relative reductions in 5-year-relapse and death rates were approximately 35%
      and 17%, respectively. Intraportal perfusion of the liver in an adjuvant
      perioperative setting seems to be of similar benefit. Preliminary data of the
      adjuvant therapy with 5-FU and folinic acid also show that this combination seems
      to have at least the same efficacy as the current standard 5-FU/levamisole in the
      adjuvant therapy of colon cancer. At the current time, patients with colon cancer
      of Dukes stage C should be offered adjuvant chemotherapy with 5-FU/levamisole
      outside of clinical studies.

PMID- 7501920
TI  - [Diet therapy in cancer].
AB  - Cancer cachexia is a syndrome with weight loss, anorexia, and loss of host body
      cell mass. Tumor cachexia may be an early symptom of a neoplasm. Low food intake
      is the main reason for weight loss. Surgery, chemotherapy and radiation remain
      primary therapeutic modalities to overcome cancer cachexia. Artificial nutrition
      is able to avoid progressive weight loss; nutrition alone may not preserve fat
      free body cell mass. Parenteral nutrition reduces perioperative morbidity and
      mortality. Nutritional support failed to show a benefit in patients with
      malignancies which are treated with therapeutic radiation or chemotherapy. For
      patients with unresectable neoplasms of the upper GI-tract conventional
      palliative regimens (bougienage, laser, etc.) do not support a satisfactory
      nutritional state. Ambulatory enteral tube feeding via percutaneous endoscopic
      gastrotomy (PEG) as an adjunct to therapy is useful and safe in providing
      adequate fluid and substrates.

PMID- 7501921
TI  - [Interdisciplinary therapy of anal carcinoma].
AB  - Primary radiation therapy is a safe sphincter sparing treatment for anal
      carcinomas less than 4 cm. In larger tumors results have improved dramatically in
      recent years by use of chemoradiation. Simultaneous radiochemotherapy of anal
      carcinoma leads to a 5-year survival rate of 80% with only 3 to 8% severe side
      effects, a local control of 75% and a conservation of sphincter function in 80%.
      If the tumor is smaller than 4 cm, radiotherapy alone is sufficient in patients
      with contraindications for chemotherapy; however, the risk of severe late side
      effects increases to 10%. A colostomy is indicated in patients with severe or
      complete stenosis of the anal canal with incontinence or obstruction by the
      tumor, in case of tumor nonresponding to radiotherapy or inoperable with painful
      defecation. Abdominoperineal resection should be limited to residual tumors
      increasing two months after radiotherapy, to salvage after relapse, to fistulas
      and necroses developing as complications of radiotherapy, to ulcers and fecal
      incontinence and to cases of a extended primary tumor (T4). Clinically suspicious
      lymph nodes should be biopsied. Histologically positive inguinal nodes should be
      treated with radiochemotherapy without groin dissection. A monthly follow-up is
      necessary in cases with residual tumor. If the size of the tumor increases, a
      biopsy is indicated. In case of relapse a second radiochemotherapy should be
      considered. Otherwise an abdominoperineal resection is indicated.

PMID- 7501922
TI  - [Bare DNA as a new vaccine against HIV--DNA as vaccine].

PMID- 7501923
TI  - [Trends in skin cancers in the Vaud canton, 1976-1992].

PMID- 7501924
TI  - [Current knowledge of epidermal carcinogenesis].

PMID- 7501925
TI  - [Diagnosis, treatment and follow-up of primary malignant skin melanoma].

PMID- 7501926
TI  - [Malignant tumors of the skin].

PMID- 7501927
TI  - [Role of ranitidine in the treatment of peptic diseases].

PMID- 7501928
TI  - [Cellular mechanism of gastric acid secretion and mode of action of inhibiting
      drugs].

PMID- 7501929
TI  - [Ranitidine: consequences on secretory function and gastric mucosa].

PMID- 7501930
TI  - [Role of ranitidine in the treatment of gastroesophageal reflux and its
      complications].

PMID- 7501931
TI  - [Role of ranitidine in duodenal ulcerous disease].

PMID- 7501932
TI  - [Importance of ranitidine in the eradication of Helicobacter pylori].

PMID- 7501933
TI  - [Role of ranitidine in the treatment and prevention of NSAID-induced digestive
      lesions].

PMID- 7501934
TI  - [Deglutition disorders: from videofluoroscopy to rehabilitation].
AB  - Dysphagic patients present with swallowing difficulties that should be precisely
      localized and quantified in order to provide a specific rehabilitation. This
      paper describes a simple yet complete videofluoroscopy protocol with emphasis on
      each step of the swallowing process, in order to assess sequentially the
      physiopathology of the involved organs. A comparison is also established between
      the videofluoroscopy results and the specific rehabilitation to be cared by the
      swallowing pathologist.

PMID- 7501936
TI  - [Routine thoracic radiography at admission to a psychogeriatric hospital: why
      continue to perform such a procedure when it has but little effect on
      treatment?].

PMID- 7501935
TI  - [Deglutition disorders: choice of diet and compensatory posture].
AB  - Swallowing difficulties are most often evaluated by videofluoroscopy and treated
      by a pluridisciplinary team. Each patient requires individual rehabilitation
      depending on the anatomical or physiological etiology of the dysphagia. After
      discussing the indirect therapy (1) which is geared to improve the muscular
      function, the choice of diet and the compensation postures are systematically
      reviewed.

PMID- 7501937
TI  - [Descriptive study of a stay in Treatment and Rehabilitation Centers in Vaud.
      Characteristics of the patients and developments].

PMID- 7501938
TI  - [Response to the article: "In the 50s patients have been irradiated to death just
      for experiment sake". by P.H. Hufschmid. Appeared in the Nouveau Quotidien of 26
      June 1995].

PMID- 7501939
TI  - [Contribution of imaging in thoracic surgery].

PMID- 7501940
TI  - [Curative antifungal treatment of invasive pulmonary aspergillosis].
AB  - Pulmonary invasive aspergillosis is a frequent and poor prognosis complication of
      immunodeficiency and prolonged neutropenia. Its treatment is usually based on
      amphotericin given as intravenous infusion at 1 to 1.25 mg/kg/d. Use of lipid
      carriers give the opportunity to administrated higher dose, 5 mg/kg/d, with
      respect of renal function and good results in the primarily study. Intraconazole
      is now a good therapy after amphotericin, in the second time of disease.

PMID- 7501941
TI  - [Pulmonary lymphangiomyomatosis. Long-term benefit of anti-estrogen treatments
      remains uncertain].
AB  - Lymphangiomyomatosis is a rare disease which affects young women of childbearing
      age. Ten women with pulmonary lymphangiomyomatosis were treated with antiestrogen
      therapy from 3 to 9 years (mean time of treatment: 5.3 years). Efficacy of
      treatment was evaluated by clinical, radiological, pulmonary function testing
      response as well as the overall long-term outcome. Four patients died of
      respiratory failure after 3, 5, 5 and 9 years of treatment. Of the 6 patients
      remaining alive, respiratory function deteriorated in 4 cases after a transient
      period of mild improvement lasting 3 years in 2 cases. Two patients appeared
      stable after 3 and 7 years of treatment. Without a control group, although a
      longer time of survival along these last years, it seems difficult to impute this
      benefit to the sole antiestrogen treatment and the overall long term prognosis of
      the disease remains really uncertain.

PMID- 7501942
TI  - [Alveolar proteinosis: diagnosis and therapeutic management. Apropos of 2 cases].
AB  - Two cases of pulmonary alveolar proteinosis are reported. Emphasis is placed on
      imaging techniques for diagnosis with bronchofibroscopy and bronchoalveolar
      lavage. Treatment of symptomatic forms is based on classical alveolar lavage with
      a rigid bronchoscope or currently with the fibroscope.

PMID- 7501943
TI  - [Endo-bronchial lipoma. Apropos of a case].
AB  - We report a case of an endobronchial lipoma on a 63 year-old woman, treated
      surgically. A literature review allows us to show the importance of fiberoptic
      bronchoscopy and computerized tomography in the diagnosis of this kind of benign
      tumors. The different aspects of treatment with recent progress represented by
      endoscopic resection are studied.

PMID- 7501944
TI  - [Two complications of bullous emphysema. Apropos of a case].
AB  - Infection and cancer are two classical complications of bullous emphysema. We
      report the case of a 47-year-old patient who presented a tuberculous infection
      then cancer within less than one year interval. The questions concerning
      diagnosis of infection are discussed. Pyogenic germs are usually involved and
      tuberculosis much less often. Exceptionally atypical mycobacteria, notably
      xenopi, are rarely the cause. The diagnosis can be particularly difficult in case
      of haemorrhage or cancer on bullae. The diagnosis of cancer in bullous emphysema
      is also studied. The relationships between tuberculosis and cancer in bullous
      emphysema are discussed.

PMID- 7501946
TI  - [ORL cancer and suspected bronchial lesion].

PMID- 7501945
TI  - [Disappearance of emphysematous bullae after infectious episodes].
AB  - The authors report 3 cases of peri-emphysematous lung infection associated with
      the development of air-fluid level in pre-existing emphysematous bullae.
      Prolonged observation revealed that both bullae and fluid disappeared completely
      or partially after short antibiotic treatment. The review of literature show that
      this favourable evolution has not often been described and that these pictures
      must be to differentiate from lung abscess.

PMID- 7501947
TI  - [Multiple spinal cord metastases of small cell bronchial cancer. Role of
      chemotherapy].

PMID- 7501948
TI  - [From a service charter to a public health service charter].
AB  - The official publication of the Charter of Public Health Service in Italy (19th
      may 1995) prompted a series of positive reactions, as it has been seen as an
      indicator of a new attention given to consumers' rights. The document is examined
      by underlining the aspects which could provide a specific opportunity for the
      nursing personnel to develop a closer role of ally for patients' rights.

PMID- 7501949
TI  - [Quality: the many meanings of a word].

PMID- 7501950
TI  - [Intensive care and resuscitation: visits to hospitalized patients].
AB  - The nurse's opinion and their feelings and attitudes toward the parents visits in
      coronary (CCU) and intensive care (ICU) units was evaluated. A questionnaire with
      closed questions was sent to 60 coronary care and intensive care units
      respectively. 50 questionnaires (41.6% were returned). Patients access to the
      wards is very dishomogeneous, with greater variability among ICUs. On average,
      patients are allowed to visit their relatives 1.35 hour/day, divided in two entry
      times. Only in 19% of wards (38 wards) there are exceptions to these rules.
      Nurses are not allowed to give any kind of information to relatives in 25% of
      wards, because this is considered a doctors' task. Probably the part of the
      limitations to the access of the relatives are due to organizative problems, but,
      according to the nurses, there are major opportunities for improvement.

PMID- 7501951
TI  - [Home care for the diabetic within the limits of project--object: pilot project
      integrated into the health education of the diabetic. Veneto Region].
AB  - Twenty one district-nurses working in 13 districts were handed a questionnaire
      (one questionnaire for each patient), to collect data on nursing interventions
      and main problems of the 382 diabetic patients cared for. The diabetic patients
      are a very demanding population with a mean age of 78 years; 314 (82%) have a
      comorbidity, 272 (71%) severe limits on their physical functioning and 233 (61%)
      the diabetic foot; 183 patients (47%) are not capable of taking autonomous
      decisions. The nursing interventions for these patients are both technical
      (drawing blood samples, diagnostic exams) and educational on how to manage and
      monitor self-administration of insulin (31 patients, 10%), on self monitoring
      techniques (116 patients, 30%), on alimentation in general and change in food
      habits (289 patients, 94.1%). The role of the nurse in promoting patients'
      independence and in preventing complications is highlighted.

PMID- 7501952
TI  - [Research methods and instruments: analysis of various articles].
AB  - Research papers published on some of the most well known medical and nursing
      journals are presented and discussed. The main aim of the contribution, which
      opens a new arena for discussion on the Rivista dell'Infermiere is to critically
      appraise published research works focusing both on strengths and novelty as well
      as weaknesses in the hypothesis formulation, methods and instruments used,
      discussion of the results. A critical analysis should enable nurses to start
      learn to read and eventually write a research protocol, possibly avoiding some
      common mistakes.

PMID- 7501954
TI  - [Fifty years ago, Hiroshima].

PMID- 7501953
TI  - [Fever in children: what is new?].

PMID- 7501955
TI  - [Rising temperatures and health risks].

PMID- 7501956
TI  - Comparison of acute hepatocellular proliferating cell nuclear antigen labeling
      indices and growth fractions, p34cdc2 kinases, and serum enzymes in carbon
      tetrachloride-treated rats.
AB  - We evaluated various biomarkers associated with cell proliferation immediately
      following insult with the classic hepatotoxicant carbon tetrachloride (CCl4).
      Rats were administered a single necrogenic dose of CCl4 and euthanized at either
      t = 4, 8, 12, 16, or 24 hr postdose. Parameters evaluated included the following:
      immunohistochemical detection of hepatocellular proliferating cell nuclear
      antigen labeling indices (PCNA-LIs; percentage of cells in S phase) and growth
      fractions (PCNA-GFs; percentage of cells in the cell cycle); PCNA and the cyclin
      dependent kinase p34cdc2 (CDK) protein in S-9 fractions by Western blot and
      enzyme-linked immunosorbent assay (ELISA); and liver-related serum enzymes. An
      increase in PCNA-GF was observed at t = 4 hr, concomitant with elevations in CDK
      and PCNA protein (Western blot). PCNA-LIs were increased by t = 24 hr, as were
      CDK and PCNA by ELISA. Sorbitol dehydrogenase was the most sensitive enzyme, with
      increases observed at t = 4 hr. Our results indicate that PCNA-GF, CDK, and PCNA
      levels reflect hepatocellular regeneration as early as 4 hr following CCl4
      insult. We conclude that these assays are early and sensitive indicators of acute
      hepatotoxicity that may be advantageous to evaluate in the early stages of
      exploratory studies.

PMID- 7501957
TI  - Carcinogenicity of dietary dimethylnitrosomorpholine, N-methyl-N'-nitro-N
      nitrosoguanidine, and dibromoethane in rainbow trout.
AB  - Eighteen-mo feeding trials of rainbow trout were used to test the carcinogenicity
      of 5 chemicals in this species. A single exposure level was used for each
      substance. The doses and chemicals tested were 1,556 ppm 2,6
      dimethylnitrosomorpholine (DMNM), 500 ppm N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG), 2,000 ppm 1,2-dibromoethane (DBE), 2,000 ppm 1,1-dichloroethylene (DCE),
      and 200 ppm cyclophosphamide (CP). Liver and/or glandular stomach neoplasms were
      produced by DMNM (liver and stomach), MNNG (stomach), and DBE (chiefly, stomach
      tumors). In addition, DMNM produced a low incidence of swimbladder papillomas and
      caused testicular atrophy in 50% of treated males. DCE and CP produced no
      neoplasms at the exposure levels used. No evidence of other chronic toxicity was
      seen for any of the 5 compounds.

PMID- 7501958
TI  - Age-related neoplasia in a lifetime study of ad libitum-fed and food-restricted
      B6C3F1 mice.
AB  - Longevity, body weight, and age-specific neoplasia were determined in 1,064
      B6C3F1 mice as part of a coordinated study of food restriction (FR). Restricted
      animals were offered 60% of the diet consumed by the ad libitum (AL) group.
      Longevity data were derived from a set of 56 animals of each sex from each diet
      group, which were examined whenever dead or moribund. For cross-sectional data, a
      parallel set of 210 animals were sacrificed in groups of 12-15 at 6-mo intervals.
      Lifetime body weight was reduced in the FR mice approximately proportional to
      restriction (i.e., 40%). Food restriction increased the age at 50% survival
      (median) by 36% in both sexes and increased the maximal lifespan (mean age of
      oldest 10%) by 21.5% in males and by 32.5% in females. In 56 males of the
      longevity groups, there were 89 neoplasms in the AL subgroup versus 53 in FR; 56
      AL females had 100, versus 58 in 55 FR females. Increase in lifespan of the
      restricted animals was achieved primarily by decrease in incidence and delay of
      onset of fatal tumors, of which lymphoma was the most prominent. This report
      catalogs all of the neoplasms (1,103) observed in longevity and cross-sectional
      groups, by diet, sex, and age. These data add to the existing knowledge base
      needed for future studies of dietary restriction and aging as well to evaluate
      nutrition of animals used in bioassays.

PMID- 7501959
TI  - Olfactory toxicity of methimazole: dose-response and structure-activity studies
      and characterization of flavin-containing monooxygenase activity in the Long
      Evans rat olfactory mucosa.
AB  - Methimazole is a compound administered to humans for the treatment of
      hyperthyroidism and is used experimentally as a model substrate for the flavin
      containing monooxygenase (FMO) system. Previous results from this laboratory
      demonstrated that methimazole is an olfactory system toxicant, causing nearly
      complete destruction of the olfactory epithelium in the male Long-Evans rat
      following a single ip dose of 300 mg/kg. The present studies were undertaken to
      determine the dose-response relationship for methimazole-induced olfactory
      mucosal damage and to determine whether or not similar damage occurs as a result
      of oral administration, mimicking the relevant route of human exposure. We also
      investigated the mechanism of olfactory toxicity of methimazole by means of a
      structure-activity study and began the characterization of the form(s) of FMO
      present in the olfactory mucosa of the male Long-Evans rat. Dose-response
      analysis demonstrated that methimazole causes olfactory mucosal damage at doses
      of 25 mg/kg ip and greater. The results of gavage studies showed that a single
      oral dose of 50 mg/kg also caused olfactory mucosal damage. Two structurally
      related compounds, methylimidazole and methylpyrrole, were not olfactory
      toxicants, suggesting that a reactive intermediate generated in the course of
      metabolizing methimazole to an S-oxide is the olfactory toxic species. Microsomal
      incubation studies revealed the presence of methimazole S-oxidation activity in
      olfactory mucosal microsomes at levels comparable to those in liver. An anti
      mouse liver FMO antibody reacted on Western blots with olfactory mucosal
      microsomes. These findings demonstrate a dose-response for the olfactory toxicity
      of methimazole and suggest that characterization of human olfactory mucosal FMO
      activity may be necessary to assess the potential for human risk associated with
      therapeutic exposure to methimazole.

PMID- 7501961
TI  - The pharmacologic basis of the cardiovascular toxicity of minoxidil in the dog.
AB  - Minoxidil (MNX), like several other vasoactive drugs, causes cardiovascular
      toxicity in dogs by undetermined mechanisms. We studied the mechanism of
      cardiovascular toxicity of MNX [an adenosine triphosphate (ATP)-sensitive
      potassium channel opener] by blocking its pharmacologic effects with glyburide
      (an ATP-sensitive potassium channel blocker) in groups of 5 female beagle dogs
      treated orally for 2 days with 1.0 mg/kg/day of MNX alone or with glyburide given
      in 5 or 6 divided doses of 300 mg/kg at 2 hr before and after each dose of MNX
      and at 3-6-hr intervals thereafter. A third group of 5 dogs received glyburide
      alone in the same dosing regimen as in the combination group. Mean arterial
      pressure (MAP), heart rate (HR), the pharmacokinetics of MNX, and gross and
      microscopic changes in the heart were evaluated. Glyburide did not influence the
      pharmacokinetics of MNX but prevented or markedly attenuated the MNX-induced
      cardiovascular lesions (right atrial hemorrhagic lesions, subendocardial
      necrosis, or coronary arteritis) occurred in dogs whose MNX-induced hemodynamic
      effects were effectively blocked by glyburide. In conclusion, the cardiovascular
      toxicity of MNX in dogs is not caused by a direct toxic effect of MNX on the
      heart but apparently is related to the exaggerated pharmacologic/profound
      hemodynamic effects it elicits in the dog.

PMID- 7501960
TI  - S-(1,2-dichlorovinyl)-L-cysteine-induced nephrotoxicity in the New Zealand white
      rabbit: characterization of proteinuria and examination of the potential role of
      oxidative injury.
AB  - S-(1,2-dichlorovinyl)-L-cysteine (DCVC)-induced nephrotoxicity in vivo was
      investigated in New Zealand White rabbits. A primary emphasis in these studies
      was further characterization of DCVC-induced nephrotoxicity using a variety of
      serum and urinary analytes, including sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). Additionally, the role of oxidative injury was
      assessed to address the dichotomy between reports indicating that such a
      mechanism is important in vivo and those indicating that such mechanisms do not
      contribute substantially to the mechanism of effects observed in vitro. Urine was
      collected prior to and at 8 and 24 hr after iv administration of DCVC. Serum was
      collected 15 min prior to and 24 hr after DCVC administration. Rabbits were
      euthanized 24 hr post-DCVC administration, and kidneys were fixed in formalin and
      further processed for light microscopic examination. DCVC (10 mg/kg, iv) induced
      a 45-50-fold increase in total urinary protein excretion, a 10-15-fold increase
      in urinary N-acetyl-beta-D-glucosaminidase concentration, plus a marked
      glucosuria by 24 hr postadministration. Additionally, DCVC increased serum
      creatinine levels by about 2-fold, with a trend toward increased blood urea
      nitrogen. SDS-PAGE analysis of rabbit urine confirmed the clinical finding of
      marked proteinuria in DCVC-treated animals, which in contrast to previously
      reported data was due to the presence of both low and high molecular weight
      proteins. Antioxidants had no significant effect on DCVC-dependent renal injury,
      nor was there evidence for DCVC-induced lipid peroxidation, as measured by either
      thiobarbituric acid-reactive substances or a commercial assay for malondialdehyde
      and hydroxalkenals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7501962
TI  - Liver lesions in rats associated with wrapping of the torso.
AB  - Liver lesions were noted in control and dosed rats from a percutaneous toxicity
      study that involved wrapping of the torso to prevent oral ingestion following
      dermal application of test articles. Further investigation in a follow-up study
      revealed that the liver lesions were related to wrapping of the torso rather than
      to test-article administration because the liver lesions only appeared in wrapped
      animals, including sham-treated controls, but not in naive control animals. The
      liver lesions, which included centrilobular coagulative necrosis, inflammatory
      cell infiltration around biliary tracts, histiocytosis, fibrosis, and
      granulomatous inflammation, were compatible with infarction and associated
      inflammatory and reparative changes. There was no discernible pattern of
      involvement of specific hepatic lobes or regions of lobes. Many of the lesions
      were sufficiently severe to be considered life-threatening. This potentially
      significant complication should be considered when developing study protocols
      that involve wrapping of the torso of rats, and consideration should be given to
      inclusion of a naive control group that is not wrapped.

PMID- 7501964
TI  - Spontaneous vascular neoplasms in aged Sprague-Dawley rats.
AB  - Primary benign and malignant vascular neoplasms occurred spontaneously in 8 of
      710 male (1.1%) and 4 of 710 female (0.6%) Crl:CD Br strain Sprague-Dawley rats
      employed in two 2-yr oncogenicity studies (1,400) and as controls in a 1-yr
      toxicity study (20). Four of 13 neoplasms were found in the spleen; skin and
      kidney each had 2 neoplasms. Single vascular neoplasms were in the liver,
      testicle, uterus, mesenteric lymph node, and vagina. Hemangioma was more common
      (5 males, 2 females) than hemangiosarcoma (3 males, 2 females). Vascular
      neoplasms were considered the cause of death in 2 females, both with
      hemangiosarcomas involving the spleen or kidney. One male had 2 primary
      hemangiomas in separate organs. Vascular neoplasms are infrequently reported
      [1/82 females (1.2%), 1961; 9/880 both sexes (1.0%), 1985] in this rat strain.
      The incidence of vascular neoplasms of this report was higher in males (9) than
      in females (4), in contrast to incidences reported in the literature.

PMID- 7501963
TI  - Immunomodulatory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin tested by the
      popliteal lymph node assay.
AB  - Drugs and other chemicals that have the potential to induce or exacerbate
      systemic autoimmune diseases in humans are of great concern. The aim of this
      study was to examine the immune-disregulating potential of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) by using the popliteal lymph node (PLN) assay.
      Chlorpromazine (CPZ) was used as a reference compound for 2 reasons: (a) CPZ is
      known to elicit a positive response in this assay, and (b) CPZ is a structural
      analogue of TCDD. Male Sprague-Dawley rats were injected subcutaneously with
      either TCDD or CPZ into the right hind footpad, whereas vehicle alone was
      injected into the contralateral footpad. Control rats were injected with vehicle
      in both hind footpads. Animals were sacrificed on day 7, and their PLNs were
      removed, weighed, and immersed in 10% formalin. The PLN weight index (the weight
      ratio of right PLN over left PLN) was significantly higher in both CPZ- and TCDD
      treated rats than in controls. Histological examinations of PLNs in the CPZ- and
      TCDD-treated rats revealed similar morphological changes in both groups (e.g.,
      mild follicular hyperplasia with no evidence of an acute inflammatory response).
      These results indicate that TCDD has the potential to induce or exacerbate
      autoimmune-like reactions. Results also suggest that drugs may be useful
      surrogates to study the mechanism of toxicity of environmental chemicals that
      cannot be administered to humans.

PMID- 7501965
TI  - 1,3,5-Trinitrobenzene-induced encephalopathy in male Fischer-344 rats.
AB  - Administration of 1,3,5-trinitrobenzene (TNB) to male Fischer-344 rats produced
      ataxia after 6 or 7 oral doses (71 mg/kg). Light microscopic examination after 10
      days revealed petechial hemorrhages in the brain stem and cerebellum and
      bilaterally symmetric degeneration and necrosis (malacia) with reactive gliosis
      in the cerebellar peduncles. The malacia was dorsal and lateral to the fourth
      ventricle involving the cerebellar nuclei, medial and lateral vestibular nuclei,
      and inferior colliculi. Blood vessels associated with the lesion had widened
      Virchow-Robin spaces, occasionally with extravasated erythrocytes. Rats
      administered daily oral doses of 35.5 mg/kg of TNB for 10 days and 35.5 and 71
      mg/kg of TNB for 1 or 4 days did not have brain lesions.

PMID- 7501966
TI  - A toxicologic pathologist's view of apoptosis or I used to call it necrobiosis,
      but now I'm singing the apoptosis blues.

PMID- 7501967
TI  - Importance of serum CA 125 levels in malignant peritoneal mesothelioma.
AB  - Elevated levels of CA 125 have been shown to be present in the serum of patients
      with ovarian carcinoma, non-gynaecological cancers and some benign diseases.
      However, the value of CA 125 in malignant peritoneal mesothelioma has not been
      studied in detail. Therefore, 7 patients with diffuse malignant mesothelioma were
      included in this study. Median age was 52.4 (range 16-73), and 6 of them were
      women. The mean serum CA 125 level was 308 kU/l (range 8-1,300 kU/l). Serum CA
      125 concentrations were found to be elevated in all 6 female patients. In 3
      patients, serum CA 125 levels were followed prospectively and showed a very close
      correlation with the response to chemotherapy. In 2 responder patients, initially
      elevated CA 125 levels returned to normal during remission after chemotherapy. In
      1 non-responder patient, the serum CA 125 level continued to rise. In conclusion,
      the serum CA 125 level might be helpful in the diagnosis and follow-up of
      malignant peritoneal mesothelioma.

PMID- 7501968
TI  - Normal and malignant trophoblasts do not recruit granulated metrial gland cells.
AB  - A possible relationship between the development of granulated metrial gland (GMG)
      cells and trophoblast was studied. Trophoblast implanted in ectopic sites (e.g.
      kidney capsule) did not induce decidua and did not recruit GMG cells. Only when
      injected in utero did trophoblast lead to the development of decidua and to the
      recruitment of GMG cells. With malignant trophoblast (choriocarcinoma cells)
      similar results were obtained as with normal trophoblast both after ectopic or
      after in utero injection. The presence of decidua, but not the development of a
      conceptus or the outgrowth of trophoblast, seems to be required for the
      differentiation of GMG cells.

PMID- 7501969
TI  - Usefulness of prostate-specific antigen density as a diagnostic test of prostate
      cancer.
AB  - To evaluate the diagnostic usefulness of prostate-specific antigen density (PSAD)
      in prostate cancer (PC) prostate-specific antigen (PSA) concentrations were
      measured in 175 patients with benign prostatic hypertrophy (BPH) and 50 patients
      with PC. Patients with BPH were classified according to the presence of
      complications of the disease: urinary infection or the presence of a bladder
      catheter. PSAD levels were observed to be greater than 0.15 in 3% of the patients
      with uncomplicated BPH and in 40% of the patients with complicated BPH. PSA
      levels were higher than 10 micrograms/l in 3 and 27% of these patients,
      respectively. High levels of PSAD were observed in 80% of the patients with
      cancer. Sixty-four percent of the patients with cancer presented PSA levels
      greater than 10 micrograms/l. These results indicate that PSAD is a useful
      parameter in the differential diagnosis of PC and BPH with the diagnostic
      efficacy of PSAD being greater than that of the serum determination of PSA.

PMID- 7501970
TI  - Cytogenetic studies in renal cell carcinoma patients receiving low-dose
      recombinant interleukin-2-based immunotherapy.
AB  - A variety of cytogenetic aberrations have been reported in sporadic and familial
      renal cell carcinoma. Rearrangements of the short arm of chromosome 3 (3p),
      trisomy 17, and nuclear hyperdiploidy have been reported to be common clonal
      chromosome changes. We analyzed a total of ten tumor-derived cell lines from
      patients who underwent nephrectomy for renal cell carcinoma employing
      conventional cytogenetics. All patients received an immunomodulatory therapy
      based on recombinant interleukin-2 (rIL-2). Tumor stage and grade, histo- and
      cytopathology, and patients' response to immunotherapy were assessed and
      correlated statistically to rearrangement of 3p, trisomy 17, and nuclear
      hyperdiploidy. Trisomy 17 as clonal aberration could be revealed only in
      papillary renal cell carcinoma, whereas tumors with compact or tubulopapillary
      growth pattern lacked this abnormality (p < 0.002). One of 3 patients with
      diploid or near-diploid karyotype (< or = 49 chromosomes) achieved a partial
      remission while two presented with stable disease after immunotherapy. In
      contrast, all 6 patients with tumor progression upon rIL-2-based immunotherapy
      revealed hyperdiploid (> 49 chromosomes) karyotypes. The correlation between
      hyperdiploidy and tumor progression was found to be statistically significant (p
      < 0.029). Interestingly, the only patient achieving an objective tumor remission
      after immunotherapy presented with a normal diploid karyotype. Our findings
      suggest tumor hyperdiploidy as an adverse prognostic factor in renal cell
      carcinoma patients receiving rIL-2-based immunotherapy.

PMID- 7501971
TI  - Up-regulation of HOXC6, HOXD1, and HOXD8 homeobox gene expression in human
      neuroblastoma cells following chemical induction of differentiation.
AB  - An early event in the pathogenesis of neuroblastoma (NB), a tumor derived from
      embryonal neural crest tissue, appears to be the arrested differentiation of
      neuroblasts. However, NB cells can be induced to differentiate in vitro with
      numerous chemicals including retinoic acid (RA) and dibutyryl cyclic AMP (db
      cAMP). One family of transcription factors, encoded by the homeobox (HOX) genes,
      plays a crucial role in Drosophila, Xenopus, and mammalian embryonic
      differentiation and development. We have previously identified six HOX genes
      (HOXC6, HOXC8, HOXD1, HOXD4, HOXD8, and HOXD9), by a sensitive PCR-based
      approach, in a cDNA library prepared from the human LA-N-5 NB cell line induced
      to differentiate with RA. In this report, we studied the regulation of these six
      HOX genes in a series of NB cell lines chemically induced to differentiate.
      Untreated NB cells express low or undetectable levels of HOX mRNA, and HOXC8
      remains undetectable in the induced cells. However, a significant induction of
      HOXC6, HOXD1, and HOXD8 expression is seen in the RA-treated NB cell lines,
      albeit with different patterns and degree of up-regulation. db-cAMP treatment
      also induced HOXC6 and HOXD8 expression in two of the three NB cell lines
      analyzed. Low levels of HOXD4 and HOXD9 induction were observed in two and one RA
      treated NB cell line, respectively. Up-regulation of HOXC6, HOXD1, and HOXD8
      expression in human NB cells, chemically induced to differentiate, appears to be
      associated with maturation toward a differentiated neuronal phenotype.

PMID- 7501972
TI  - Estrogen activates migration potential of endometrial cancer cells through
      basement membrane.
AB  - The migration potential through a basement membrane in an endometrial cancer cell
      line, such as Ishikawa, HEC-1-A or HHUA cell, in terms of strength, was enhanced
      by estradiol, but not modified by progesterone, medroxyprogesterone acetate
      (MPA), danazol or tamoxifen alone, by which estradiol-enhanced migration
      potential was inhibited. The order of the level of estrogen receptor was Ishikawa
      > HEC-1-A > HHUA cells. Therefore, it is suggested that the invasiveness of
      endometrial cancer cells might be activated by estradiol via estrogen receptors,
      but inactivated by progesterone, MPA, danazol or tamoxifen as an antiestrogen
      action, and that endometrial cancer cells could become invasive in the estrogen
      predominant milieu, and the antiestrogenic agents could protect it.

PMID- 7501973
TI  - Expression of the double-stranded RNA-dependent protein kinase (p68) in human
      breast tissues.
AB  - P68 is a potent inhibitor of protein synthesis in virally infected cells and has
      been suggested to function in noninfected cells as a tumor suppressor gene. We
      have previously demonstrated that p68 expression correlates directly with
      cellular differentiation and inversely with proliferative activity in normal
      epithelium and in several human tumor systems. In order to determine the role of
      p68 in human breast cancer, we utilized immunohistochemistry and mapped the
      expression of p68 in tissue from 200 breast biopsy specimens. A total of 434
      foci, ranging from normal breast tissue to infiltrating carcinoma were examined.
      We found that p68 was present at basal levels in normal lobular and luminal
      ductal epithelial cells, with higher levels present in myoepithelial cells.
      Nonproliferative fibrocystic lesions showed variable expression of p68, with high
      levels seen within foci of apocrine metaplasia and low levels in cystically
      dilated terminal duct units. Low levels of p68 were seen in typical ductal
      proliferations, lobular neoplasia (atypical lobular hyperplasia and lobular
      carcinoma in situ), and in fibroadenomas. Foci of atypical ductal hyperplasia in
      situ and invasive ductal carcinoma generally showed higher levels of p68
      expression. Among the infiltrating carcinomas, p68 expression correlated with
      nuclear grade. This suggests that the ability of p68 to inhibit cellular
      proliferation may be impaired in breast cancer and that its expression, although
      modestly paralleling cellular differentiation, is not a predictive indicator of
      improved survival.

PMID- 7501975
TI  - Ethics in action. Departing from normal emergency guidelines in subtle ways.

PMID- 7501974
TI  - Field effect of human colon carcinoma on normal mucosa: relevance of
      carcinoembryonic antigen expression.
AB  - Human colon cancer usually develops on a mucosa which has already undergone
      multiple steps of genetic change. These multiple steps create a field effect
      characterized by the presence of morphologically normal, but biologically altered
      epithelial cells. This aims of this study were to evaluate whether the expression
      of carcinoembryonic antigen (CEA) can act as a phenotypic marker of the field
      effect, and to map its topography in relation to the presence of colorectal
      adenocarcinoma. The expression of CEA was tested by immunohistochemistry on
      morphologically normal mucosa at 4 increasing distances from 14 autologous cases
      of colorectal adenocarcinoma. CEA expression in the normal mucosa was compared to
      the tumor. The results show that in the mucosa adjacent to the edge of the
      autologous tumor, CEA is expressed to the same level as displayed in the
      carcinoma; there is a decrease in CEA expression in normal mucosa located at 1 cm
      or more from the edge of carcinoma. Mucosa sampled at 5 and 10 cm from the tumor
      expresses CEA at the same low level as in mucosa of control subjects with no
      colorectal neoplasm. In conclusion, this study demonstrates a gradient of CEA
      expression in the peritumoral area, supporting the concept of field effect, and
      maps its extent. These data are relevant to the biology of human colorectal
      cancer, and more practically, to the optimal location of surgical resection.

PMID- 7501976
TI  - Cut your patients' risk of nosocomial UTI.

PMID- 7501977
TI  - Don't dismiss whiplash.

PMID- 7501978
TI  - Hyperkalemia.

PMID- 7501979
TI  - Smell disorders = danger.

PMID- 7501980
TI  - 1995 earnings survey. You can't bank on benefits.

PMID- 7501981
TI  - If you're asked to be a health proxy.

PMID- 7501982
TI  - Co-meditation: guiding patients through the relaxation process.

PMID- 7501983
TI  - Always learning.

PMID- 7501984
TI  - What to suggest for migraine headache.

PMID- 7501985
TI  - You need to help addicts like me.

PMID- 7501986
TI  - Atomic force microscopy of nucleoprotein complexes.
AB  - Recent data on the AFM studies of nucleoprotein complexes of different types are
      reviewed in this paper. The first section describes the progress in the sample
      preparation methods for AFM studies of nucleic acids and nucleoprotein complexes.
      The second part of this paper reviews AFM data on studies of complexes of DNA
      with regulatory proteins. These studies include two different types of DNA
      distortion induced by proteins binding: local bending of DNA at sites of protein
      binding and formation of large loops due to protein-protein interactions between
      molecules bound to distant sites along the DNA molecules (DNA looping). The
      prospects for use of AFM for physical mapping of genomes are discussed in this
      section as well. The third part of the paper reviews data on studies of complexes
      of DNA with non-sequence specific binding proteins. Special emphasis is given to
      studies of chromatin which have resulted in progress in the understanding of
      structure of native chromatin fiber. In this section, novel data on AFM studies
      of RecA-DNA filaments and complexes of dsRNA with the dsRNA-specific protein p25
      are also presented. Discussion of the substrate preparation procedures in
      relation to the AFM studies of nucleoprotein complexes is given in the final
      section.

PMID- 7501987
TI  - Scanning force microscopy of chromatin.
AB  - Scanning force microscopy (SFM) is a new method to obtain the topography of
      surfaces with nanometer-resolution. The ability to image under liquids makes the
      technique attractive for biological applications, especially for the
      determination of the ultrastructure of biomolecules under native conditions. One
      growing field of interest is the investigation of chromatin and chromatin-related
      structures. Different levels of chromatin condensation were the subject of
      several previous SFM investigations, from the nucleosomal chain, to the 30-nm
      fiber, ending with the metaphase chromosome. The SFM yielded new information on
      such fundamental problems as the core spacing of the nucleosomal chain, the
      internal structure of the 30-nm fiber and the banding mechanism of metaphase
      chromosomes. Other investigations dealt with the SFM characterization of polytene
      chromosomes. This paper reviews the state-of-the-art in SFM chromatin research
      and discusses future developments in this field.

PMID- 7501988
TI  - Cross-linking of cell surface receptors as a trigger or cell apoptosis and
      proliferation.
AB  - A hypothesis of the mechanisms by which the protein cross-linking agents trigger
      apoptosis of lymphoid cells and proliferation of other cell types is proposed. It
      is assumed that both effects are triggered by aggregation of receptors on cell
      surface, which results from their cross-linking. This idea is substantiated by
      the example of one of these agents, ionizing radiation. As in the case of
      physiological agents, such as, antigens and growth factors, the aggregation of
      receptors induced by radiation activates receptor protein tyrosine kinases from
      which the signal is transduced to genes through protein kinase C. The hypothesis
      is consistent with the relationship between these effects and the PTK-PKC
      dependent signal transduction pathway and its activation after irradiation.

PMID- 7501989
TI  - X-irradiation-induced disorganization of cytoskeletal filaments and cell contacts
      in HT29 cells.
AB  - Organization of cytoskeleton and cell contacts were studied by immunochemistry
      and electron microscopy in confluent HT29 cultured cells following exposure to
      0.5 and 1.0 Gy doses of X-ray. Microtubules were resistant to irradiation,
      whereas, the actin and intermediate filaments disrupted rapidly following the
      treatment and their components appeared as clumps of actin and cytokeratin
      aggregates in the cytoplasm as demonstrated by immunochemistry. Loss of cell
      contacts and decrease in the number of desmosomes was also characteristic of
      irradiated cells. Electron microscopy revealed intact desmosomes in control cells
      and abnormal desmosomes in the irradiated samples characterized by the absence of
      tonofilaments. The perinuclear filament network and cortical filaments were well
      detectable by electron microscopy. Under the effect of irradiation, the
      perinuclear filaments almost disappeared and, at the same time, small bundles of
      filaments were formed irregularly in the cytoplasm associated with amorphous
      material.

PMID- 7501990
TI  - Confocal laser scanning microscopic studies on alveolar bone remodeling with
      orthodontic tooth movement and retention.
AB  - Alveolar bone reconstruction in growing dog during the retention period following
      orthodontic tooth movement was studied. Three beagle dogs (8-10 kg body weight,
      about one-year-old) were used and two of the animals were subjected to
      histological observation. The upper 2nd and lower 3rd premolars on both sides
      were extracted prior to the orthodontic treatments. After a healing period of one
      month, the upper 3rd premolar and the lower 4th premolar on the right side were
      moved mesially with a conventional orthodontic force for 8 weeks, and then
      retained in their new position for 4 weeks. The contralateral corresponding
      premolars were used as control. The alveolar bone was double-labeled with
      tetracycline (TC) during the movement and calcein (Cal) during the retention
      period. Alveolar bone structure and labeling patterns were examined by contact
      microradiography, conventional fluorescence microscopy, and confocal laser
      scanning microscopy (CLSM). Optimizing the separation of TC and Cal labelings in
      the alveolar bone was attained by the simultaneous use of ultraviolet (364 nm)
      and argon (488 nm) laser sources for excitation of TC and Cal, respectively. Cal
      labeling, indicative of new bone deposition showed two distinct patterns:
      lamination at the periodontal surface and rings circumscribing the vascular
      canal. The cementum surface also exhibited active deposition during the
      experimental period. Bone formation was affected by slight changes in magnitude
      and direction of orthodontic or occlusal forces. CLSM is valuable in deciphering
      the process of alveolar bone remodeling.

PMID- 7501991
TI  - Endoarticular loose bodies and calcifications of the disk of the
      temporomandibular joint: morphological features and chemical composition.
AB  - We studied articular disks and endoarticular loose bodies taken from patients
      suffering from different types of temporomandibular joint (TMJ) pathology. The
      scanning electron microscopy (SEM) analysis of the disks and the endoarticular
      loose bodies was followed by a chemical-compositional analysis using an energy
      dispersive spectrometer (EDS) and by characterization of the crystalline phases
      by X-ray powder diffraction (XRD). The articular disks were composed of a central
      radiopaque area lacking any evident structural features, surrounded by compact
      bundles of collagen fibers. EDS and XRD analyses showed that endodiscal radio
      opaque areas were hydroxyapatite. By SEM, we observed a fibrous network only in
      circumscribed areas of the endoarticular loose bodies. The chemical-compositional
      analysis showed that the loose bodies were composed of calcite (CaCO3). The
      results of this investigation, along with the clinical history of the patients,
      allow us to formulate some hypotheses regarding the etiopathogenesis of these
      structural anomalies. The endodiscal calcifications could be the result of a
      chronic inflammatory process that produces displastic alterations of the
      articular disk. Moreover, an acute inflammatory process with modifications in the
      mechanisms of the synovial fluid turnover seems to be the event that leads to the
      formation of endoarticular loose bodies.

PMID- 7501992
TI  - Scanning electron microscopy and energy dispersive spectroscopy analysis of
      calciotraumatic lines in rat labial dentin after acute exposure to strontium
      chloride.
AB  - Rats were given strontium chloride (SrCl2) intraperitoneally at a dose of 500
      mg/kg. The upper incisors were removed after injection of strontium. These
      incisors were studied by scanning electron microscopy-energy dispersive
      spectroscopy analysis (SEM-EDS) and light microscopy to examine the
      calciotraumatic lines of strontium in the rat incisor labial dentin. At 24 hours
      after injection of strontium, the calciotraumatic response was observed in the
      predentin using hematoxylin and eosin (H-E) staining. At 5 days, three layers of
      calciotraumatic lines were present in the labial dentin using an H-E staining and
      backscattered electron imaging in the SEM. The external layer consisted of
      unmineralized dentin, the intermediate layer of relatively unmineralized dentin,
      ane the internal layer of unmineralized dentin. By SEM-EDS analysis, strontium
      was detected in these layers. The elemental dot map showed that the external and
      internal unmineralized layers had a low calcium content. The magnesium
      concentration was higher in the internal unmineralized layer than the external
      unmineralized layer.

PMID- 7501993
TI  - The interaction of laser energy with ureter tissues in a long-term investigation.
AB  - This study investigates tissue responses after laser irradiation of the rabbit
      ureter, which serves as an experimental model for rectourogenital fistulae of
      children. Twenty-five rabbit ureters were irradiated intraluminally by a Nd:YAG
      laser 1320 nm (2 Watt, 20 seconds and 3 Watt, 8 seconds) via an applicator with
      radialsymmetrical light distribution. Immediately, 2 weeks, 4 weeks, 8 weeks, and
      16 weeks after irradiation, the ureters were X-rayed with contrast solution and
      prepared for light and transmission electron microscopy. For the parameters
      employed, no apparent morphological differences could be observed. Immediately,
      the central laser zone showed a transmural thermonecrosis prevailed by cellular
      destruction, condensed ground substance and occlusion of most vascular lumina.
      Peripheral laser zones displayed urothelial vacuolations. Between 2 and 16 weeks,
      urothelial regeneration and ingrowth of granulation tissue caused a luminal
      stenosis or occlusion followed by transformation into scar tissue. In some
      peripheral laser zones, a hydroureter with marked luminal dilatation developed.
      We conclude that the ureter is occluded if the expanding force of the growing
      scar tissue exceeds the hydrostatic pressure of the obstructed urine. A laser
      occlusion of rectourogenital fistulae will be easier to achieve since fistula
      occlusion does not entail an obstruction of the urine flow.

PMID- 7501994
TI  - In situ hybridization and monoclonal antibody analysis of plasma membrane Ca-pump
      mRNA and protein in submandibular glands of rabbit, rat and man.
AB  - The degree of supersaturation of saliva with calcium (Ca) is related to the
      mineral phase of enamel in erupted teeth, the incidence of caries, and the
      formation of calculus. The mechanisms for regulating salivary Ca concentration
      are therefore of relevance to dentistry. Sections of rabbit, rat and human
      submandibular gland (SMG) were processed for immuno-histochemistry with a
      specific anti-plasma membrane Ca-pump antibody, 5F10. Western blots confirm that
      the molecular weight of the proteins identified by our antibody (135 kDa) is
      consistent with an appropriate molecular weight for PMCA antigen (135-150 kDa).
      Tissue sections were also processed for in situ hybridization to study the
      distribution of the PMCA mRNA isoforms. In mammals, the PMCA1 gene is reported to
      code for a PMCA protein with a role in maintaining the intracellular Ca levels in
      both epithelial and non-epithelial cells. Other genes including the PMCA2 and
      PMCA4 genes may code for PMCA proteins specific to Ca transporting tissues. Our
      studies demonstrate cytoplasmic labeling of PMCA mRNA with hPMCA-1 and hPMCA-4
      specific cDNA probes in humans, and rPMCA-1 and rPMCA-2 specific oligonucleotide
      probes in rats. Labeling of PMCA protein and all mRNA isoforms was found in the
      cytoplasm of the interlobular and intralobular ducts (except for intercalated
      ducts). The demonstrated presence of PMCA in SMGs of rabbit, rat, and man, may
      suggest a role for PMCA in the regulation of intracellular Ca and in a mechanism
      for regulating and maintaining the high concentration of Ca in salvia.

PMID- 7501995
TI  - Comparative analysis of patch lesions in the chick inner ear following acoustic
      trauma: optical versus scanning electron microscopy.
AB  - Neonatal chicks were exposed to an octave band noise with a center frequency of
      1.5 kHz at 116 dB SPL for 4 hours. Seven days following overstimulation, the
      birds were sacrificed. Their basilar papillae were removed, fixed in 4%
      paraformaldehyde, and processed in two steps. First, the ears were immunostained
      with a supernatant of mouse anti-tectorial membrane antibodies, followed by a
      diaminobenzidine process. Examinations of the papillae under an optical stereo
      microscope revealed a patch site with a partially regenerated tectorial membrane
      (referred to as the honeycomb). After the optical studies, the same ears were
      post-fixed in 1% osmium tetroxide, dehydrated in ethanol, and processed for
      scanning electron microscopy (SEM). SEM examinations demonstrated a honeycomb
      covered patch lesion in the papilla. Patch lesion perimeters were traced from
      both the optical and SEM images, and patch areas were calculated. Also, papilla
      height was measured at the midpoint of the inner ear in both groups. These
      calculations showed that the patch area and papilla height had shrunk by
      approximately 37% and 33%, respectively, following the SEM methodology. The
      decrease in these dimensions may be attributed to several steps required for the
      SEM specimen preparation, such as critical point drying.

PMID- 7501997
TI  - Improved methods for preserving macromolecular structures and visualizing them by
      fluorescence and scanning electron microscopy.
AB  - To determine the optimal procedures to preserve cytoskeletal and other
      macromolecular structures for microscopic studies we have evaluated the effects
      of various methods to extract cultured cells. In this report, we compare results
      using different fixatives, crosslinking reagents, and permeabilization methods on
      (1) the labeling of cells for fluorescence microscopy with phalloidin or antibody
      against tubulin; and (2) the morphological preservation of macromolecular
      structures for scanning electron microscopy. Maximal labeling of F-actin with
      phalloidin was obtained by fixing cells in 4% paraformaldehyde (PFA) and labeling
      the unextracted cells with methanolic phalloidin, whereas maximal labeling of
      tubulin required prefixation with either PFA or the bifunctional protein
      crosslinking reagent, dithiobis (succinimidylpropionate) (DSP) and extraction
      with ethanol or Triton in a high salt buffer. However, for both qualitative and
      quantitative light and electron microscopic studies of intracellular
      macromolecular structures, prefixation with DSP and extracting with Triton X-100
      in a stabilizing buffer is the overall method of choice for both labeling and
      morphological studies. Although other methods provide maximal labeling or
      preservation of specific structures, this method provides excellent preservation
      of morphological structure while allowing proteins to be preserved and labeled by
      specific probes.

PMID- 7501996
TI  - Comparison of DNA fragmentation and color thresholding for objective quantitation
      of apoptotic cells.
AB  - Apoptosis is a process of cell death characterized by distinctive morphological
      changes and fragmentation of cellular DNA. Using video imaging and color
      thresholding techniques, we objectively quantitated the number of cultured CD4+ T
      lymphoblastoid cells (HUT78 cells, RH9 subclone) displaying morphological signs
      of apoptosis before and after exposure to gamma-irradiation. The numbers of
      apoptotic cells measured by objective video imaging techniques were compared to
      numbers of apoptotic cells measured in the same samples by sensitive apoptotic
      assays that quantitate DNA fragmentation. DNA fragmentation assays gave
      consistently higher values compared with the video imaging assays that measured
      morphological changes associated with apoptosis. These results suggest that
      substantial DNA fragmentation can precede or occur in the absence of the
      morphological changes which are associated with apoptosis in gamma-irradiated RH9
      cells.

PMID- 7501998
TI  - Impact of Escherichia coli on urine citrate and urease-induced crystallization.
AB  - Escherichia coli (E. coli) is usually not a urease producer. It is, however,
      often cultured in urinary phosphate containing calculi including ammonium
      magnesium phosphate stones. This suggests the possibility that E. coli might be
      involved in stone forming process. The effect of E. coli on urine citrate and
      urease-induced crystallization in human urine has been studied in vitro. E. coli
      was found to strongly reduce urine citrate (after 48 hours). In the E. coli
      inoculated samples, the urease-induced crystallization was increased. There was a
      strong correlation, r = 0.8, between the citrate decrease and the increase in
      calcium precipitation. The results indicate that E. coli and the reduced urine
      citrate influences urease-induced crystallization in vitro.

PMID- 7501999
TI  - Backscattered electron imaging and energy-dispersive X-ray microanalysis studies
      of evidence for calcium salt heterogeneity in fifteen gallstones from an elderly
      human.
AB  - We examined 15 variably-sized gallstones, taken from an elderly male, by
      backscattered electron imaging and energy-dispersive X-ray microanalysis to learn
      the structural and distribution patterns of gallstone calcium (Ca-) salts. Of the
      13 cholesterol-rich stones, nine stones had peripheral concentric layers of Ca
      carbonate, whereas 2 stones had peripheral layers of Ca-phosphate. No Ca-salts
      were detected from 2 cholesterol-rich stones. The 2 stones containing Ca
      phosphate had no Ca-salt cores, whereas the stones containing Ca-carbonate were
      separated into 3 different types: two stones with a Ca-carbonate core, four
      stones with several Ca-bilirubinate cores of glass-like structure, and 3 stones
      lacking Ca-salt cores. A closer view of the Ca-salt layers, which may be
      occasionally coexistent with Ca-bilirubinate, mainly showed either laminate
      deposits or numerous globules with a few laminae. Of the 2 cholesterol-poor
      stones, one had dispersed particles mainly of Ca-phosphate, and the other had
      loosely dispersed particles with small amounts of Ca-phosphate, bilirubinate,
      and/or palmitate. Some relationship between the size and Ca-salt species of these
      gallstones was suggested. Gallstones collected from the same individual showed a
      considerable heterogeneity of Ca-salts.

PMID- 7502001
TI  - [Treatment of severe asymptomatic carotid stenosis].
AB  - Severe (reduction of vessel diameter by more than 70%) asymptomatic carotid
      artery stenosis is associated with a risk of cerebrovascular accident of 2-5% in
      the year following diagnosis. Results of large, prospective, randomized studies
      suggest that prophylactic carotid endarterectomy may be beneficial in this
      situation. However, the elements that must be taken into consideration before
      deciding to operate on an individual patient are extremely complex. Age and
      comorbidity (especially cardiovascular conditions) must be considered, as well as
      perioperative risk and expected medium- and long-term benefits, as compared with
      optimal conservative treatment. Decision analysis may be of considerable help in
      such a complex situation by considering objectively and explicitly all these
      epidemiologic and individual variables. Specifically, the technique makes it
      possible to simulate threshold probabilities of perioperative complications above
      which the risks of prophylactic endarterectomy outweigh its benefit, expressed as
      5-year survival free of cerebrovascular event. These thresholds are 4%, 3% and 2%
      for a patient aged 65, 75 and 85 respectively. If 2-year event-free survival is
      considered, the surgical risk should not exceed 1.5% for a patient aged 65 years
      or 1% above that age. This type of analysis makes it possible to individualize
      the guidelines of international panels of experts, but ultimately the decision to
      operate or not must also consider the psychological profile of the patient and
      his attitude towards risk ("risk-seeking or risk-averse").

PMID- 7502000
TI  - [Treatment of symptomatic carotid stenosis].
AB  - Published results and experience at the University Hospital of Zurich clearly
      indicate that in patients with severe, symptomatic carotid artery stenosis the
      benefits of carotid endarterectomy clearly outweigh the risks. Surgical treatment
      also favorably influences outcome in cases with contralateral carotid artery
      occlusion.

PMID- 7502002
TI  - [Value of interventional angiology in carotid stenosis].
AB  - Available results indicate that transluminal angioplasty of the internal carotid
      artery represents an interesting new alternative for the treatment of patients
      with symptomatic severe stenosis of the carotid artery. The procedure offers an
      advantage in patients with stenosis that is not accessible by the surgical
      approach and in patients with high surgical risk. Furthermore neurological signs
      can be continuously monitored during the procedure, allowing its interruption if
      necessary. There is a need for prospective studies assessing risk and benefit of
      this procedure in comparison with alternative therapies.

PMID- 7502003
TI  - [Management of patients with carotid stenosis and coronary heart disease].
AB  - Coronary and carotid atherosclerosis are often coexistent in the same patient.
      Therefore, patients presenting with carotid stenosis should be screened for
      coronary heart disease and vice versa. Patients with significant asymptomatic or
      symptomatic carotid stenosis have an elevated perioperative risk of cerebral
      ischemic attacks during operations with extracorporeal circulation and of
      myocardial infarction during carotid endarterectomy. The operations should be
      performed simultaneously, with carotid endarterectomy being done before
      sternotomy. This yields mortality and morbidity rates comparable with those for
      isolated operations on extracorporeal circulation. Medical therapy for such
      patients consists of platelet inhibitors with adequate cardiac medication.

PMID- 7502004
TI  - [Angioplasty or bypass for multitruncal coronary disease. Viewpoint of the
      cardiologist].
AB  - When multivessel coronary disease requires revascularization, a choice must be
      made between percutaneous angioplasty and bypass surgery. Angioplasty is
      considerably less invasive and does not require a prolonged hospital stay.
      Nevertheless, it is less effective for longstanding coronary occlusions and is
      limited by a restenosis rate of 20 to 40% which often means a new intervention.
      At the present time, surgery remains the standard mode of therapy in a large
      proportion of patients with multivessel disease. However, the procedure is more
      complex than the percutaneous approach and long-term venous graft attrition
      remains an unresolved issue. Surgery and angioplasty have been compared in
      several randomized and prospective studies which are reviewed here. The results
      of these comparisons, while useful for current clinical decision-making, will
      require reassessment in the future to take into account the predictable
      improvements in safety, efficacy and long-term results of percutaneous
      techniques.

PMID- 7502005
TI  - [PTCA or bypass surgery in multi-vessel coronary disease? Viewpoint of the
      surgeon].
AB  - Recently several randomized studies have been devoted to a comparative analysis
      of angioplasty (PTCA) versus bypass surgery (CABG) in patients with multivessel
      coronary disease. Even though only a very limited number of the screened patients
      could be randomly assigned to undergo PTCA or CABG (less than 10% of the subjects
      originally evaluated), some valid conclusions may be drawn. With regard to
      perioperative mortality, no significant difference between the two treatment
      groups was evident; considering the incidence of peri-interventional myocardial
      infarction, a trend towards a slightly higher risk could be detected for the
      surgical patients (EAST and GABI trials). The most striking differences between
      the two procedures have been completeness of revascularization and incidence of
      restenosis. Thus, in the EAST and ERACI trials complete revascularization was
      achieved only in 75% and 51% respectively of the PTCA patients as compared with
      99% and 88% respectively for the CABG patients. Beyond all doubt, the greatest
      drawback of PTCA is the occurrence of restenosis; in multivessel angioplasty
      several arterial segments are by definition exposed to development of narrowing
      at the site of PTCA, resulting in a higher risk of restenosis per patient. In a
      major angiographic study 50% of patients showed significant restenosis in at
      least one PTCA segment, and in 14% multiple restenosis were found. The occurrence
      of restenosis is a substantial reason for the high incidence of further
      interventions following multivessel angioplasty; thus, in the EAST trial only 46%
      of the PTCA patients did not require a subsequent revascularization procedure
      (versus 87% in the surgical group). Economic aspects do not counterbalance the
      limited efficacy of multivessel angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502006
TI  - [Arterial stenting versus vascular replacement].
AB  - Stenting or transluminal implantation of vascular endoprostheses is a new
      modality among many endovascular techniques. Experience is greatest in the iliac
      arteries where patency rates above 90% are reported. Because in femoropopliteal
      arteries the patency rates are below 70%, stents should be implanted only in
      situations where percutaneous transluminal angioplasty (PTA) alone has failed.
      Similar results are obtained with implantation in renal and supraaortic arteries.
      Application in great veins for palliation of tumor compression seems to be a good
      indication. A new perspective opens up with "covered stents" to treat aorto-iliac
      aneurysms endoluminally. Even though stenting is still experimental in some
      regards, and open surgical reconstruction represents the established standard, it
      has great therapeutic potential. However, endovascular techniques should neither
      be rejected nor simply adopted by vascular surgeons but developed further in a
      team approach with experienced interventional angiologists and radiologists.

PMID- 7502007
TI  - [Coronary angioplasty versus aortocoronary bypass surgery in older patients. Role
      of coronary angioplasty].
AB  - In elderly patients, who need to be treated increasingly for coronary artery
      disease, medical therapy is more difficult and the risks of coronary artery
      bypass graft surgery are markedly increased. PTCA is an alternative treatment
      with the aim of removing the culprit coronary artery lesion to relieve symptoms
      and improve quality of life rather than to achieve full revascularization in
      order to prolong life. Experiences and risks of PTCA compared to those of
      coronary artery bypass graft surgery in this special group of patients are
      described and discussed.

PMID- 7502008
TI  - [Cardiac surgery in octogenarians].
AB  - 37 patients aged 80 or over underwent cardiac surgery during an 11-year period.
      Operative indications included angina, dyspnea and syncope. The majority of
      patients (n = 32) had a left ventricular ejection fraction greater than 0.5.
      There were 28 aortic valve procedures, of which seven were combined with coronary
      artery bypass grafts (CABG), and 2 with mitral valve repair; in addition, 7
      isolated CABG procedures and one isolated mitral valve repair were performed. 36
      day mortality was 5.4% (2 patients); 9 patients died at a later date (2.5 to 118
      months after surgery). The most frequent postoperative complications were atrial
      fibrillation, pulmonary infection or atelectasis, transient delirium and
      atrioventricular conduction disturbances. Mean hospital stay was 14.5 days. 1-
      and 5-year actuarial survival rates were 83% and 57%. In a control group of
      patients aged 60-69 matched for preoperative characteristics, there were no in
      hospital fatalities and 1- and 5-year survival were, respectively, 100% and 82%.
      Among complications, only conduction disturbances and transient delirium were
      significantly more frequent in the octogenarian group. At follow-up, the
      proportion of severely symptomatic octogenarians had diminished to 24% from 84%.
      In conclusion, cardiac surgery can be performed on octagenarians with adequate
      myocardial reserve, exposing them to a perioperative mortality that is in the
      range of younger age groups while offering an equivalent prospect for functional
      improvement.

PMID- 7502009
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). Angiocardiography
      in congenital heart defects. 1948].

PMID- 7502010
TI  - [Molecular medicine and gene therapy as exemplified with arteriosclerosis and
      restenosis].
AB  - Atherosclerosis and its consequences account for most morbidity and mortality in
      Western countries. Atherosclerosis develops over a period of decades and has a
      complex pathogenesis. It is a disease of the intima and primarily involves four
      cell types, i.e. endothelial and vascular smooth muscle cells, monocytes and
      platelets. In recent years, elucidation of the cellular and molecular mechanisms
      of these cells, and their alterations by cardiovascular risk factors and in
      atherosclerosis, has markedly expanded knowledge of this disease. In particular,
      it became clear that endothelial cells play a crucial role in the regulation of
      platelet function and coagulation, as well as vascular tone and structure.
      Interestingly, endothelial dysfunction occurs early on in the presence of
      cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes.
      This could lead to adhesion of circulating platelets and monocytes, increased
      accumulation of lipids in the subintima, increased contraction, migration and
      proliferation of vascular smooth muscle cells. The fact that atherosclerosis
      develops only in some but not in other parts of the circulation, however, has
      rarely been considered. With the development of molecular biology it has now
      become possible to clone differentially expressed genes in vessels with or
      without atherosclerosis; this in turn makes it possible to characterize better
      the molecular and cellular mechanisms of the disease. The search for such
      candidate genes could form the basis for future genetic interventions. This
      therapeutic approach is likely to assume clinical importance, particularly in
      monogenetic diseases (i.e. familial hypercholesteremia), while its use in complex
      polygenetic diseases such as atherosclerosis is more difficult. Restenosis,
      however, may be accessible to gene therapy earlier on as it is accessible to
      local gene transfection.

PMID- 7502011
TI  - [Mitral valvuloplasty using the Inoue balloon].
AB  - Percutaneous mitral balloon valvuloplasty (PMBV) is an accepted alternative
      treatment to open and closed mitral commissurotomy or mitral valvular
      replacement. The Inoue technique has become standard in most centers. In our
      first 24 percutaneous balloon mitral valvuloplasties by the Inoue technique, 23
      procedures were technically successful. The mean age of the patients was 53 (24
      75) years. There were 22 women. Four patients had a history of closed mitral
      commissurotomy, one of previous mitral balloon valvuloplasty, and one of aortic
      metallic valve replacement. The mean echocardiographic mitral Wilkins score was
      7.3 (range 4-13). PMBV resulted in significant improvement of hemodynamic values.
      The mean mitral pressure gradient fell from 12 +/- 5 to 5 +/- 3 mm Hg (p =
      0.0001) and the cardiac index increased from 2.7 +/- 0.7 to 3.0 +/- 0.8 l/min/m2.
      The valve area by the Gorlin formula increased from 1.2 +/- 0.3 to 2.1 +/- 0.6
      cm2 (p = 0.0001). Doppler and planimetric echocardiography data were in keeping
      with hemodynamic data. Mitral valve regurgitation increased by more than 1 grade
      in 3 patients, 2 of whom subsequently underwent valve replacement. No tamponade
      occurred with the Inoue technique. There was 1 fatal outcome following tamponade
      and emergency heart surgery after mitral valvuloplasty with a Trefoil balloon
      employed in a subsequent intervention due to impossibility of placing the Inoue
      balloon. Left-to-right shunting at the atrial level after the intervention was
      not significant in any patient. 21 patients (88%) had improvement in their
      functional class. One of the patients with unchanged functional class had late
      onset of severe mitral regurgitation, another had a technical failure with the
      Inoue technique, and in 1 patient with calcified valve leaflets significant
      mitral stenosis persisted. At 3 to 15 months follow-up echocardiography was
      performed in 19 patients: mitral valve areas had not changed significantly
      compared to post-interventional values. One patient had a new mitral
      regurgitation compared with the situation immediately after PMBV. Mitral balloon
      valvuloplasty by the Inoue technique is an effective treatment with low risk in
      patients with symptomatic mitral stenosis.

PMID- 7502012
TI  - [Systemic fibrosis (generalized form of Ormond's disease). Report of a case which
      achieved complete remission with cyclophosphamide and corticosteroids].
AB  - A 51-year-old engineer was admitted with progressive lower back pain which had
      started 4 months before. We found an elevated ESR and anemia. Chest X-ray showed
      bilateral polycyclic thickening of the pleura, and abdominal CT examination
      revealed a paraaortic tumorous lesion and a solid kidney tumor with a diameter of
      5 cm on the left side. During the course of the disease we also observed an
      infiltration in the apex of the upper lobe of the left lung. Histological
      examination showed fibrotic tissue typical of Ormond's disease in the kidney
      tumor as well as in the pulmonary infiltrate. We diagnosed a systemic form of
      retroperitoneal fibrosis. Treatment with cyclophosphamide (combined with
      prednisone during the first 4 months) resulted in complete remission of the
      disease.

PMID- 7502014
TI  - [Scientific raisins from 125 tears SMW (Swiss Medical Weekly). Spindle cell
      carcinoma of the kidney 16 years following Thorotrast pyelography. 1949].

PMID- 7502015
TI  - Gonadotropin control of follicle and oocyte maturation: implications for
      ovulation induction.
AB  - Development and maturation of follicles and oocytes during the menstrual cycle
      are complex processes that are poorly understood. Current gonadotropin therapy
      for ovulation induction/IVF may result in the production of suboptimal oocytes.
      As we learn more about the interdependency of follicle and oocyte in natural
      cycles, we should enhance our ability to produce better quality oocytes in
      artificial cycles. This will lead to improved success in the treatment of
      infertility.

PMID- 7502013
TI  - [Hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the
      world. The profile of risk factors associated with HCC includes not only chronic
      infection with hepatitis B virus and/or hepatitis C virus with subsequent
      cirrhosis, but also metabolic and alcoholic chronic liver diseases. While the
      risk of developing cancer is high in patients with cirrhosis, the aim of most
      screening programmes is to detect small, potentially resectable tumors. Serum
      alpha 1-fetoprotein lacks both sensitivity and specificity as a screening test
      and two-thirds of patients with small HCCs have levels below 200 ng/ml. Hepatic
      resection or liver transplantation at an early stage of HCC, without extrahepatic
      metastasis, provide complete cure of the disease.

PMID- 7502016
TI  - On chance and compromise.

PMID- 7502018
TI  - Ketogenic diet for seizure control.

PMID- 7502017
TI  - Pheochromocytoma associated with polycythemia: case report.
AB  - Secondary polycythemia has been noted in association with various neoplasms. An
      erythropoiesis stimulating factor (erythropoietin) has been demonstrated in the
      fluid or tissues obtained from most of these neoplasms and erythropoietin levels
      were found to be elevated in the serum and returned to normal after resection of
      these tumors. Recently, the potential of pheochromocytoma to produce a wide
      variety of hormones and neurotransmitters such as growth hormone, motilin, ACTH,
      atrial natriuretic factor (ANF) and others has been shown. Although elevated
      hematocrit has been observed in association with pheochromocytomas, the
      occurrence of absolute polycythemia in such cases is very rare. In this report,
      we describe a patient with a long history of hypertension and cardiac dysrhythmia
      as well as polycythemia which was secondary to pheochromocytoma. The patient's
      blood pressure normalized and the polycythemia regressed after resection of the
      tumor. Increased release of erythropoietin is the most favored explanation for
      this rare association. Pheochromocytoma should be included in the differential
      diagnosis of secondary polycythemia.

PMID- 7502019
TI  - Test animals and risk.

PMID- 7502020
TI  - Test animals and risk.

PMID- 7502021
TI  - Test animals and risk.

PMID- 7502022
TI  - Tamoxifen ruling in California.

PMID- 7502023
TI  - Glucocorticoids.

PMID- 7502024
TI  - Lyme disease study.

PMID- 7502025
TI  - MBP and innate immunity.

PMID- 7502026
TI  - EMF studies.

PMID- 7502027
TI  - Medical imaging.

PMID- 7502028
TI  - New clues found to Huntington's.

PMID- 7502029
TI  - Biosphere 2 turned over to Columbia.

PMID- 7502031
TI  - Asian hominids grow older.

PMID- 7502030
TI  - Scientists attacked for 'patenting' Pacific tribe.

PMID- 7502032
TI  - African origins: west side story.

PMID- 7502033
TI  - Do Kenya tools root birth of modern thought in Africa?

PMID- 7502034
TI  - Annual genetics meeting: some puzzles, some answers.

PMID- 7502035
TI  - AIDS research. New drug shows promise in monkeys.

PMID- 7502036
TI  - Agriculture finds a niche; drug researchers seek help.

PMID- 7502037
TI  - Epidemiology. China's unique environment favors large intervention trials.

PMID- 7502038
TI  - Unraveling immune privilege.

PMID- 7502039
TI  - ATP-sensitive K+ channels: paradigm lost, paradigm regained.

PMID- 7502040
TI  - Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea
      receptor.
AB  - A member of the inwardly rectifying potassium channel family was cloned here. The
      channel, called BIR (Kir6.2), was expressed in large amounts in rat pancreatic
      islets and glucose-responsive insulin-secreting cell lines. Coexpression with the
      sulfonylurea receptor SUR reconstituted an inwardly rectifying potassium
      conductance of 76 picosiemens that was sensitive to adenosine triphosphate (ATP)
      (IKATP) and was inhibited by sulfonylureas and activated by diazoxide. The data
      indicate that these pancreatic beta cell potassium channels are a complex
      composed of at least two subunits--BIR, a member of the inward rectifier
      potassium channel family, and SUR, a member of the ATP-binding cassette
      superfamily. Gene mapping data show that these two potassium channel subunit
      genes are clustered on human chromosome 11 at position 11p15.1.

PMID- 7502042
TI  - Fas ligand-induced apoptosis as a mechanism of immune privilege.
AB  - The eye is a privileged site that cannot tolerate destructive inflammatory
      responses. Inflammatory cells entering the anterior chamber of the eye in
      response to viral infection underwent apoptosis that was dependent on Fas (CD95)
      Fas ligand (FasL) and produced no tissue damage. In contrast, viral infection in
      gld mice, which lack functional FasL, resulted in an inflammation and invasion of
      ocular tissue without apoptosis. Fas-positive but not Fas-negative tumor cells
      were killed by apoptosis when placed within isolated anterior segments of the
      eyes of normal but not FasL-negative mice. FasL messenger RNA and protein were
      detectable in the eye. Thus, Fas-FasL interactions appear to be an important
      mechanism for the maintenance of immune privilege.

PMID- 7502041
TI  - Crystal structure of the xanthine oxidase-related aldehyde oxido-reductase from
      D. gigas.
AB  - The crystal structure of the aldehyde oxido-reductase (Mop) from the sulfate
      reducing anaerobic Gram-negative bacterium Desulfovibrio gigas has been
      determined at 2.25 A resolution by multiple isomorphous replacement and refined.
      The protein, a homodimer of 907 amino acid residues subunits, is a member of the
      xanthine oxidase family. The protein contains a molybdopterin cofactor (Mo-co)
      and two different [2Fe-2S] centers. It is folded into four domains of which the
      first two bind the iron sulfur centers and the last two are involved in Mo-co
      binding. Mo-co is a molybdenum molybdopterin cytosine dinucleotide. Molybdopterin
      forms a tricyclic system with the pterin bicycle annealed to a pyran ring. The
      molybdopterin dinucleotide is deeply buried in the protein. The cis-dithiolene
      group of the pyran ring binds the molybdenum, which is coordinated by three more
      (oxygen) ligands.

PMID- 7502043
TI  - Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the
      treatment of AIDS.
AB  - Strategies for the treatment of human immunodeficiency virus-type 1 (HIV-1)
      infection must contend with the obstacle of drug resistance. HIV-1 nucleocapsid
      protein zinc fingers are prime antiviral targets because they are mutationally
      intolerant and are required both for acute infection and virion assembly.
      Nontoxic disulfide-substituted benzamides were identified that attack the zinc
      fingers, inactivate cell-free virions, inhibit acute and chronic infections, and
      exhibit broad antiretroviral activity. The compounds were highly synergistic with
      other antiviral agents, and resistant mutants have not been detected. Zinc finger
      reactive compounds may offer an anti-HIV strategy that restricts drug-resistance
      development.

PMID- 7502045
TI  - Solution structure of a bovine immunodeficiency virus Tat-TAR peptide-RNA
      complex.
AB  - The Tat protein of bovine immunodeficiency virus (BIV) binds to its target RNA,
      TAR, and activates transcription. A 14-amino acid arginine-rich peptide
      corresponding to the RNA-binding domain of BIV Tat binds specifically to BIV TAR,
      and biochemical and in vivo experiments have identified the amino acids and
      nucleotides required for binding. The solution structure of the RNA-peptide
      complex has now been determined by nuclear magnetic resonance spectroscopy. TAR
      forms a virtually continuous A-form helix with two unstacked bulged nucleotides.
      The peptide adopts a beta-turn conformation and sits in the major groove of the
      RNA. Specific contacts are apparent between critical amino acids in the peptide
      and bases and phosphates in the RNA. The structure is consistent with all
      biochemical data and demonstrates ways in which proteins can recognize the major
      groove of RNA.

PMID- 7502044
TI  - Prevention of SIV infection in macaques by (R)-9-(2
      phosphonylmethoxypropyl)adenine.
AB  - The efficacy of pre- and postexposure treatment with the antiviral compound (R)-9
      (2-phosphonylmethoxypropyl)adenine (PMPA) was tested against simian
      immunodeficiency virus (SIV) in macaques as a model for human immunodeficiency
      virus (HIV). PMPA was administered subcutaneously once daily beginning either 48
      hours before, 4 hours after, or 24 hours after virus inoculation. Treatment
      continued for 4 weeks and the virologic, immunologic, and clinical status of the
      macaques was monitored for up to 56 weeks. PMPA prevented SIV infection in all
      macaques without toxicity, whereas all control macaques became infected. These
      results suggest a potential role for PMPA prophylaxis against early HIV infection
      in cases of known exposure.

PMID- 7502046
TI  - Inflammatory bowel disease and adenomas in mice expressing a dominant negative N
      cadherin.
AB  - Cadherins mediate cell adhesion and are essential for normal development.
      Embryonic stem cells were transfected with a dominant negative N-cadherin mutant
      (NCAD delta) under the control of promoters active in small intestinal epithelial
      cells and then introduced into C57BL/6 mouse blastocysts. Analysis of adult
      chimeric mice revealed that expression of NCAD delta along the entire crypt
      villus axis, but not in the villus epithelium alone, produced an inflammatory
      bowel disease resembling Crohn's disease. NCAD delta perturbed proliferation,
      migration, and death programs in crypts, which lead to adenomas. This model
      provides insights about cadherin function in an adult organ and the factors
      underlying inflammatory bowel disease and intestinal neoplasia.

PMID- 7502047
TI  - Concerted signaling by retinal ganglion cells.
AB  - To analyze the rules that govern communication between eye and brain, visual
      responses were recorded from an intact salamander retina. Parallel observation of
      many retinal ganglion cells with a microelectrode array showed that nearby
      neurons often fired synchronously, with spike delays of less than 10
      milliseconds. The frequency of such synchronous spikes exceeded the correlation
      expected from a shared visual stimulus up to 20-fold. Synchronous firing
      persisted under a variety of visual stimuli and accounted for the majority of
      action potentials recorded. Analysis of receptive fields showed that concerted
      spikes encoded information not carried by individual cells; they may represent
      symbols in a multineuronal code for vision.

PMID- 7502048
TI  - Pheromone response in yeast: association of Bem1p with proteins of the MAP kinase
      cascade and actin.
AB  - Haploid cells of the yeast Saccharomyces cerevisiae respond to mating pheromones
      with polarized growth toward the mating partner. This morphological response
      requires the function of the cell polarity establishment protein Bem1p.
      Immunochemical and two-hybrid protein interaction assays revealed that Bem1p
      interacts with two components of the pheromone-responsive mitogen-activated
      protein (MAP) kinase cascade, Ste20p and Ste5p, as well as with actin. Mutants of
      Bem1p that are associated with defective pheromone-induced polarized
      morphogenesis interacted with Ste5p and actin but not with Ste20p. Thus, the
      association of Bem1p with Ste20p and Ste5p may contribute to the conveyance of
      spatial information that regulates polarized rearrangement of the actin
      cytoskeleton during yeast mating.

PMID- 7502049
TI  - Requirement of Saccharomyces cerevisiae Ras for completion of mitosis.
AB  - In the yeast Saccharomyces cerevisiae, Ras regulates adenylate cyclase, which is
      essential for progression through the G1 phase of the cell cycle. However, even
      when the adenosine 3',5'-monophosphate (cAMP) pathway was bypassed, the double
      disruption of RAS1 and RAS2 resulted in defects in growth at both low and high
      temperatures. Furthermore, the simultaneous disruption of RAS1, RAS2, and the RAS
      related gene RSR1 was lethal at any temperature. The triple-disrupted cells were
      arrested late in the mitotic (M) phase, which was accompanied by an accumulation
      of cells with divided chromosomes and sustained histone H1 kinase activity. The
      lethality of the triple disruption was suppressed by the multicopies of CDC5,
      CDC15, DBF2, SPO12, and TEM1, all of which function in the completion of the M
      phase. Mammalian ras also suppressed the lethality, which suggests that a similar
      signaling pathway exists in higher eukaryotes. These results demonstrate that S.
      cerevisiae Ras functions in the completion of the M phase in a manner independent
      of the Ras-cAMP pathway.

PMID- 7502051
TI  - Attenuated retrovirus vaccines and AIDS.

PMID- 7502052
TI  - Attenuated retrovirus vaccines and AIDS.

PMID- 7502053
TI  - Attenuated retrovirus vaccines and AIDS.

PMID- 7502050
TI  - Ligand-induced autoregulation of IFN-gamma receptor beta chain expression in T
      helper cell subsets.
AB  - Interferon gamma (IFN-gamma) responsiveness in certain cells depends on the state
      of cellular differentiation or activation. Here an in vitro developmental system
      was used to show that IFN-gamma produced during generation of the CD4+ T helper
      cell type 1 (TH1) subset extinguishes expression of the IFN-gamma receptor beta
      subunit, resulting in TH1 cells that are unresponsive to IFN-gamma. This beta
      chain loss also occurred in IFN-gamma-treated TH2 cells and thus represents a
      specific response of CD4+ T cells to IFN-gamma rather than a TH1-specific
      differentiation event. These results define a mechanism of cellular
      desensitization where a cytokine down-regulates expression of a receptor subunit
      required primarily for signaling and not ligand binding.

PMID- 7502054
TI  - Attenuated retrovirus vaccines and AIDS.

PMID- 7502056
TI  - Mechanisms of cardiac fibrillation.

PMID- 7502055
TI  - Mechanisms of cardiac fibrillation.

PMID- 7502057
TI  - Authorship disputes.

PMID- 7502058
TI  - NCI AIDS budget under microscope.

PMID- 7502059
TI  - Elusive HIV-suppressor factors found.

PMID- 7502060
TI  - Breast cancer. Reanalysis confirms results of 'tainted' study.

PMID- 7502061
TI  - Long-term tamoxifen trial halted.

PMID- 7502062
TI  - RNA polymerase gets very pushy.

PMID- 7502063
TI  - AIDS tumor bank.

PMID- 7502064
TI  - How DNA replication originates.

PMID- 7502065
TI  - Protein sculptors that help turn on genes.

PMID- 7502066
TI  - Molecular machines may aid gene expression.

PMID- 7502067
TI  - The centromere: hub of chromosomal activities.
AB  - Centromeres are the structures that direct eukaryotic chromosome segregation in
      mitosis and meiosis. There are two major classes of centromeres. Point
      centromeres, found in the budding yeasts, are compact loci whose constituent
      proteins are now beginning to yield to biochemical analysis. Regional
      centromeres, best described in the fission yeast Schizosaccharomyces pombe,
      encompass many kilobases of DNA and are packaged into heterochromatin. Their
      associated proteins are as yet poorly understood. In addition to providing the
      site for microtubule attachment, centromeres also have an important role in
      checkpoint regulation during mitosis.

PMID- 7502068
TI  - Chromosomal control of meiotic cell division.
AB  - Chromosomes have multiple roles both in controlling the cell assembly and
      structure of the spindle and in determining chromosomal position on the spindle
      in many meiotic cells and in some types of mitotic cells. Moreover, functionally
      significant chromosome-microtubule interactions are not limited to the
      kinetochore but are also mediated by proteins localized along the arms of
      chromosomes. Finally, chromosomes also play a crucial role in control of the cell
      cycle.

PMID- 7502069
TI  - Telomeres: beginning to understand the end.
AB  - Telomeres are the protein-DNA structures at the ends of eukaryotic chromosomes.
      In yeast, and probably most other eukaryotes, telomeres are essential. They allow
      the cell to distinguish intact from broken chromosomes, protect chromosomes from
      degradation, and are substrates for novel replication mechanisms. Telomeres are
      usually replicated by telomerase, a telomere-specific reverse transcriptase,
      although telomerase-independent mechanisms of telomere maintenance exist.
      Telomere replication is both cell cycle- and developmentally regulated, and its
      control is likely to be complex. Because telomere loss causes the kinds of
      chromosomal changes associated with cancer and aging, an understanding of
      telomere biology has medical relevance.

PMID- 7502070
TI  - Equality for X chromosomes.
AB  - In many species, females possess two X chromosomes and males have one X
      chromosome. This difference is critical for the initial determination of sex.
      However, the X encodes many functions required equally in males and females;
      thus, X chromosome expression must be adjusted to compensate for the difference
      in dosage between the sexes. Distinct dosage compensation mechanisms have evolved
      in different species. A common theme in the Drosophila melanogaster and
      Caenorhabditis elegans systems is that a subtle alteration of chromatin structure
      may impose this modest, but vital adjustment of the X chromosome transcription
      level.

PMID- 7502071
TI  - Gametic imprinting in mammals.
AB  - Embryonic development in mammals is distinct from that in other vertebrates
      because it depends on a small number of imprinted genes that are specially
      expressed from either the maternal or paternal genome. Why mammals are uniquely
      dependent on sexual reproduction and how this dependency is dictated at a
      molecular level are questions that have been intensively investigated during the
      past 2 years. Gene inactivation experiments have confirmed predictions that
      imprinted genes regulate embryonic and placental growth and that DNA methylation
      is part of the imprinting mechanism. Despite these considerable achievements, the
      reason why imprinted hemizygosity is used as a mechanism to regulate the
      intrauterine growth of mammalian embryos remains elusive.

PMID- 7502072
TI  - Small RNA chaperones for ribosome biogenesis.

PMID- 7502073
TI  - Transcription against an applied force.
AB  - The force produced by a single molecule of Escherichia coli RNA polymerase during
      transcription was measured optically. Polymerase immobilized on a surface was
      used to transcribe a DNA template attached to a polystyrene bead 0.5 micrometer
      in diameter. The bead position was measured by interferometry while a force
      opposing translocation of the polymerase along the DNA was applied with an
      optical trap. At saturating nucleoside triphosphate concentrations, polymerase
      molecules stalled reversibly at a mean applied force estimated to be 14
      piconewtons. This force is substantially larger than those measured for the
      cytoskeletal motors kinesin and myosin and exceeds mechanical loads that are
      estimated to oppose transcriptional elongation in vivo. The data are consistent
      with efficient conversion of the free energy liberated by RNA synthesis into
      mechanical work.

PMID- 7502074
TI  - Minimization of a polypeptide hormone.
AB  - A stepwise approach for reducing the size of a polypeptide hormone, atrial
      natriuretic peptide (ANP), from 28 residues to 15 while retaining high biopotency
      is described. Systematic structural and functional analysis identified a
      discontinuous functional epitope for receptor binding and activation, most of
      which was placed onto a smaller ring (Cys6 to Cys17) that was created by
      repositioning the ANP native disulfide bond (Cys7 to Cys23). High affinity was
      subsequently restored by optimizing the remaining noncritical residues by means
      of phage display. Residues that flanked the mini-ring structure were then deleted
      in stages, and affinity losses were rectified by additional phage-sorting
      experiments. Thus, structural and functional data on hormones, coupled with phage
      display methods, can be used to shrink the hormones to moieties more amendable to
      small-molecule design.

PMID- 7502075
TI  - Sodium-driven potassium uptake by the plant potassium transporter HKT1 and
      mutations conferring salt tolerance.
AB  - Sodium (Na+) at high millimolar concentrations in soils is toxic to most higher
      plants and severely reduces agricultural production worldwide. However, the
      molecular mechanisms for plant Na+ uptake remain unknown. Here, the wheat root
      high-affinity potassium (K+) uptake transporter HKT1 was shown to function as a
      high-affinity K(+)-Na+ cotransporter. High-affinity K+ uptake was activated by
      micromolar Na+ concentrations; moreover, high-affinity Na+ uptake was activated
      by K+ (half-activation constant, 2.8 microM K+). However, at physiologically
      detrimental concentrations of Na+, K+ accumulation mediated by HKT1 was blocked
      and low-affinity Na+ uptake occurred (Michaelis constant, approximately 16 mM
      Na+), which correlated to Na+ toxicity in plants. Point mutations in the sixth
      putative transmembrane domain of HKT1 that increase Na+ tolerance were isolated
      with the use of yeast as a screening system. Na+ uptake and Na+ inhibition of K+
      accumulation indicate a possible role for HKT1 in physiological Na+ toxicity in
      plants.

PMID- 7502076
TI  - A human telomeric protein.
AB  - Telomeres are multifunctional elements that shield chromosome ends from
      degradation and end-to-end fusions, prevent activation of DNA damage checkpoints,
      and modulate the maintenance of telomeric DNA by telomerase. A major protein
      component of human telomeres has been identified and cloned. This factor, TRF,
      contains one Myb-type DNA-binding repeat and an amino-terminal acidic domain.
      Immunofluorescent labeling shows that TRF specifically colocalizes with telomeric
      DNA in human interphase cells and is located at chromosome ends during metaphase.
      The presence of TRF along the telomeric TTAGGG repeat array demonstrates that
      human telomeres form a specialized nucleoprotein complex.

PMID- 7502077
TI  - Conserved initiator proteins in eukaryotes.
AB  - The origin recognition complex (ORC), a multisubunit protein identified in
      Saccharomyces cerevisiae, binds to chromosomal replicators and is required for
      the initiation of cellular DNA replication. Complementary DNAs (cDNAs) encoding
      proteins related to the two largest subunits of ORC were cloned from various
      eukaryotes. The cDNAs encoding proteins related to S. cerevisiae Orc1p were
      cloned from the budding yeast Kluyveromyces lactis, the fission yeast
      Schizosaccharomyces pombe, and human cells. These proteins show similarity to
      regulators of the S and M phases of the cell cycle. Genetic analysis of orc1+
      from S. pombe reveals that it is essential for cell viability. The cDNAs encoding
      proteins related to S. cerevisiae Orc2p were cloned from Arabidopsis thaliana,
      Caenorhabditis elegans, and human cells. The human ORC-related proteins interact
      in vivo to form a complex. These studies studies suggest that ORC subunits are
      conserved and that the role of ORC is a general feature of eukaryotic DNA
      replication.

PMID- 7502078
TI  - Separation of origin recognition complex functions by cross-species
      complementation.
AB  - Transcriptional silencing at the HMRa locus of Saccharomyces cerevisiae requires
      the function of the origin recognition complex (ORC), the replication initiator
      of yeast. Expression of a Drosophila melanogaster Orc2 complementary DNA in the
      yeast orc2-1 strain, which is defective for replication and silencing,
      complemented the silencing defect but not the replication defect; this result
      indicated that the replication and silencing functions of ORC were separable. The
      orc2-1 mutation mapped to the region of greatest homology between the Drosophila
      and yeast proteins. The silent state mediated by DmOrc2 was epigenetic; it was
      propagated during mitotic divisions in a relatively stable way, whereas the
      nonsilent state was metastable. In contrast, the silent state was erased during
      meiosis.

PMID- 7502079
TI  - A Drosophila homolog of the yeast origin recognition complex.
AB  - Genes from Drosophila melanogaster have been identified that encode proteins
      homologous to Orc2p and Orc5p of the Saccharomyces cerevisiae origin recognition
      complex (ORC). The abundance of the Drosophila Orc2p homolog DmORC2 is
      developmentally regulated and is greatest during the earliest stages of
      embryogenesis, concomitant with the highest rate of DNA replication.
      Fractionation of embryo nuclear extracts revealed that DmORC2 is found in a
      tightly associated complex with five additional polypeptides, much like the yeast
      ORC. These studies will enable direct testing of the initiator-based model of
      replication in a metazoan.

PMID- 7502080
TI  - Early-onset epilepsy and postnatal lethality associated with an editing-deficient
      GluR-B allele in mice.
AB  - The arginine residue at position 586 of the GluR-B subunit renders heteromeric
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-sensitive glutamate
      receptor channels impermeable to calcium. The codon for this arginine is
      introduced at the precursor messenger RNA (pre-mRNA) stage by site-selective
      adenosine editing of a glutamine codon. Heterozygous mice engineered by gene
      targeting to harbor an editing-incompetent GluR-B allele synthesized unedited
      GluR-B subunits and, in principal neurons and interneurons, expressed AMPA
      receptors with increased calcium permeability. These mice developed seizures and
      died by 3 weeks of age, showing that GluR-B pre-mRNA editing is essential for
      brain function.

PMID- 7502081
TI  - Pineal serotonin N-acetyltransferase: expression cloning and molecular analysis.
AB  - Pineal serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, or AA
      NAT) generates the large circadian rhythm in melatonin, the hormone that
      coordinates daily and seasonal physiology in some mammals. Complementary DNA
      encoding ovine AA-NAT was cloned. The abundance of AA-NAT messenger RNA (mRNA)
      during the day was high in the ovine pineal gland and somewhat lower in retina.
      AA-NAT mRNA was found unexpectedly in the pituitary gland and in some brain
      regions. The night-to-day ratio of ovine pineal AA-NAT mRNA is less than 2. In
      contrast, the ratio exceeds 150 in rats. AA-NAT represents a family within a
      large superfamily of acetyltransferases.

PMID- 7502082
TI  - [Dislocated intra-articular calcaneus fractures. Long-term follow-up after open
      reposition and osteosynthesis].
AB  - A series of 98 patients with a total of 105 intra-articular fractures of the os
      calcis were operated on during a 10-year period between 1983 and 1992. We were
      able to follow up 60 patients with 64 fractures an average of 44 months (range,
      18-105 months) postoperatively. At the time of follow up, 83.9% of patients had
      been back to work, 78.6% with the same employer as before. Five of the patients
      followed up had had to retire from work; each of these had one or more severe
      coexisting injuries. A compromising nerve injury occurred postoperatively in 3
      out of 58 patients with closed fractures, in all cases following surgery with a
      medial or bilateral approach. In only 1 of the 58 patients followed up after
      closed fractures did a deep infection requiring arthrodesis occur. One patient
      had sympathetic reflex dystrophy (Sudeck). A good functional result in the lower
      ankle joint correlated with a good outcome. In contrast, postoperative
      improvement of the tuber angle and the degree of arthrosis seen radiographically
      did not. We conclude that operative repair of intraarticular calcaneal fractures
      is a procedure that can safely be procedure used to restore the ability to work
      in the majority of patients. The medial approach should preferably not be used,
      nor should the metal be extracted from the medial approach if this can be
      avoided.

PMID- 7502083
TI  - [Functional treatment of acute rupture of the Achilles tendon. An experimental
      biomechanical study].
AB  - In 84 adult rabbits the biomechanical properties of healing Achilles tendon
      rupture were examined 2, 4, 8 and 12 weeks (21 each group) after the injury. For
      the first time a mop-end-tear was performed. The following treatment modalities
      were applied (7 rabbits in each subgroup): (a) operative functional treatment
      (resorbable suture; Kleinert techniques); (b) operative functional treatment
      (fibrin glue); (c) primary functional treatment (conservative). The functional
      after treatment in all groups was performed with a specially developed orthesis,
      which was taped to the limb. For biomechanical testing a newly developed fixation
      technique (cryo-clamp) was applied, which guaranteed secure intratendineal
      rupture. After 2 weeks the fibrin glue-treated tendon ruptures showed the best
      results with regard to stiffness, tensile stress and max. rupture force. These
      results and a higher tensile stress of the sutured tendons were significantly
      different from those in the conservatively treated groups. After 4 weeks the
      stiffness in the fibrin group and the energy and rupture force in the suture
      group were significantly higher than in the group treated conservatively. The 8
      week results revealed comparable biomechanical properties. The only significant
      difference was a higher energy in the fibrin glue group than in the conservative
      treatment group. The experiment revealed no significant biomechanical differences
      after 3 months. Compared with the results recorded for plaster immobilization in
      the literature, the functional treatment resulted in a significantly faster
      course of healing.

PMID- 7502084
TI  - [Rotational instability of trochanteric femoral fractures secured with the
      dynamic hip screw. A radiologic analysis].
AB  - In this study, a retrospective analysis of patients with trochanteric fractures
      fixed with a dynamic hip screw was performed (n = 238). Analysis of the complete
      X-rays (n = 115) revealed rotation of the head-neck fragment in 12% of the cases
      (n = 14). Patients with complex fracture types were more often affected by this
      complication (p < 0.05). The distance of lateral impaction was significantly
      higher in the group with rotation of the proximal fragment compared to patients
      without rotation (p < 0.001). The rate of cutting-out (p < 0.01), the rate of
      delayed union (p < 0.01) and the rate of varus angulation (p < 0.01) was
      significantly higher. Reoperation was necessary in 14% of the patients compared
      to 2% in the group without rotation. We conclude that rotational instability of a
      gliding implant system is a severe complication in the treatment of trochanteric
      fractures.

PMID- 7502085
TI  - [Coraco-clavicular screw fixation: a simple treatment of acromioclavicular joint
      dislocation].
AB  - A series of 41 patients (average age 34 years) with acute acromio-clavicular
      joint separation were treated from 1985 to 1993 by temporary coraco-clavicular
      transfixation screw. The screw secures the anatomical position of the clavicle
      until the coraco-clavicular and the acromio-clavicular ligaments are healed.
      Follow-up was possible in 25 patients. The examination consisted in clinical and
      radiological evaluations, including assessment of subjective well-being: 24
      patients were satisfied, while 1 patient complained of minor pain at work. Follow
      up X-rays revealed mild subluxation of the acromio-clavicular joint in 5 patients
      and slight acromio-clavicular diastasis in 2. In 10 patients we found ligamentous
      calcifications. All patients had normal shoulder function. Seven patients had
      enlarged scars. Our good results indicate that this procedure can be recommended.

PMID- 7502086
TI  - [Wound drainage with a continuous high vacuum drainage system and a drainage
      system with variable vacuum].
AB  - A study of 120 total hip replacements showed the advantages of the variable
      vacuum drainage system over the continuous high vacuum drainage system. Better
      wound healing, less severe hematomas and less occlusion of drains confirmed the
      higher effectiveness of secretion draining. With regard to hygienic aspects, and
      especially to wound infection, the continuous closed drainage system is an
      improvement of the intermittent closed drainage system.

PMID- 7502087
TI  - [Abrasion reducing polyethylene ceramic-metal compound hip prosthesis head].
AB  - There are two specific problems in using metallic or ceramic heads for hip
      prostheses: (1) the amount of polyethylene abrasions in the cup caused by the
      heads (especially a metal head). (2) the polyethylene abrasions caused by Al2O3
      ceramic heads is far less than metal heads, but its ability to adapt
      geometrically is limited due to its being less strong. The abrasions appear
      because of geometric differences in the prosthetic joint, local problems in the
      surface architecture and physical/chemical interactions between the different
      materials. In this study we compare the new "Titan-Niob Ceramic Multilayer
      Sandwich Head" (built three layers of microsegregation phases and three in
      between layers of ultrathin metal, 8-10 microns thick, and a surface with
      integrated grease holes) with the common CoCrMo heads and Al2O3 ceramic heads.
      Testing 2,000,000 cycles in a bodylike liquid under permanent loads of 90 kPa,
      periodically increasing up to 250 kPa, simulating normal stress situations (i.e.,
      walking), the "Titan-Niob Ceramic Multilayer Sandwich Head" showed major
      advantages over the metal heads and also over the ceramic heads even though the
      ceramic head has been accepted so far to have the best friction coefficient.
      Furthermore, there has been no problem in surface fracture with the "Titan-Niob
      Ceramic Multilayer Sandwich Head".

PMID- 7502088
TI  - Avulsion of the anterior superior iliac spine in two adolescent sisters:
      operative versus conservative treatment.
AB  - We compared the results of treatment of identical injuries to the anterior
      superior iliac spine in two adolescent sisters, one treated conservatively and
      the other operatively. The functional results of both treatments were good, but
      the rehabilitation period was shorter with operative treatment, allowing an
      earlier return to athletic activity. Treatment by open reduction and internal
      fixation should be considered in patients requiring a short convalescence.
      Familial coincidence of avulsion fracture of the anterior superior iliac spine
      has not previously been described in the literature.

PMID- 7502089
TI  - [Fixed atlanto-axial rotational dislocation--a rare cause of torticollis in the
      child].
AB  - Two patients aged 2 and 13 years old are presented, both of whom had torticollis
      caused by atlanto-axial rotatory subluxation. The correct diagnosis was delayed
      for 3 months as a result of inappropriate radiologic evaluation. In each patient
      increased atlanto-dental distance, anterolisthesis of the atlas, and malrotation
      of the atlas relative to the axis were found on a simple lateral projection.
      Treatment, consisting in reduction under anaesthesia and plaster fixation for 8
      weeks, was successful in the smaller child, whereas redislocation occurred in the
      other patient. It is imperative to exclude by early radiological examination
      skeletal abnormality in the presence of persisting acquired torticollis in
      children.

PMID- 7502090
TI  - [Biomechanical study of the initial stability of various arthrodesis methods for
      the upper ankle joint].
AB  - Arthrodesis of the ankle joint is commonly, performed to treat severe arthritis.
      Three different techniques have been biomechanically evaluated for initial
      stability: fusion with three isolated tibio-talar lag screws (type I), which was
      inaugurated by Wagner; a second fusion technique with two isolated tibio-talar
      lag screws and an anterior tibio-talar three-hole 3.5 mm AO compression plate
      (type II); and type-II fusion with an additional lag screw through the center
      hole of the anterior plate (type III). Ten fresh cadaver ankles were used for
      biomechanical evaluation. Bone stock quality was compared before fusion by CT
      scan and osteodensitometry. Osteopenic ankle joints (bone density less than 80%
      of the median density) were excluded. Each ankle fusion was stressed with 15 Nm
      in a universal testing machine (UTS 10, Ulm, Germany) in antero-posterior and
      medio-lateral directions and in a rotational torque technique. The movements at
      the fusion gap were recorded by computer-assisted image analysis. A video camera
      recorded the displacement of four active markers on both sides of the fusion line
      during loading in real time. A computer-assisted calculation of the dislocation
      at the fusion gap was performed. This technique provides comparable results
      except for systemic failure induced by the fixation device of the testing
      machine. The results revealed comparable initial stability with types I (0.063
      mm/Nm) and III (0.074 mm/Nm; P = 0.95) ankle fusion. Type-II fusion was
      significantly less favorable concerning initial stability (0.14 mm/Nm; P < 0.01,
      Duncan's test for multiple comparisons). Our biomechanical results advertise
      isolated lag screws for ankle fusion.

PMID- 7502091
TI  - [Traumatic bone deformation in childhood, adolescence and early adulthood-
      pathomechanics and review of the literature].
AB  - Stresses applied to bones can cause plastic deformation, or bowing fractures; the
      bone is deformed by axial compression in children and by slow bending stress,
      i.e. three-point bending from the side, in young adults. Biomechanical properties
      of the bone and its plastic and elastic behaviour are discussed. We present a 14
      year-old boy with a bowing fracture of the fifth metacarpal bone.

PMID- 7502092
TI  - [Computer-assisted classification of ICD-9/10 and IKPM in compliance with the new
      federal health care regulation--practice-oriented solution for trauma surgery and
      orthopedics].
AB  - From the beginning of 1995, the German law on the health system structure
      prescribes that in all clinics the four-digit ICD code be supplied for each
      diagnosis and the ICPM code for each operation. This makes on-line access to
      diagnosis and therapy codes embedded in a clinic documentation system advisable.
      Since 1 February 1995, in one department of traumatologic surgery the ICD
      diagnosis and ICPM therapy coding is managed on-line by the doctors in the
      outpatient clinic and operation theatre, using the "do it" coding system in
      combination with the KAUZ system for clinic documentation. The user guidance
      supplied by a frequency-oriented menu and specialist traumatological terms makes
      it possible to determine the ICD and ICPM codes without any great expenditure of
      effort. Furthermore, the appropriate flat rates per case and special charges are
      displayed. Comparison of manual and computer-assisted coding of operations during
      1 month (160 patients, 173 operations) showed that manual coding could be
      corrected or improved by the computerized system in 35% of cases. The ICD-10
      system has already been integrated: it improves the recording of diagnoses and
      will simplify the change over to the coming new revision.

PMID- 7502093
TI  - The 'permanent project syndrome': a counter productive consequence of
      philanthropy.

PMID- 7502094
TI  - Global immunization and culture: compliance and resistance in large-scale public
      health campaigns.

PMID- 7502095
TI  - Global immunization--a medical perspective.
AB  - The global community is close to achieving universal childhood immunization
      against a group of important childhood diseases--measles, tuberculosis,
      diphtheria, pertussis, tetanus and polio. In addition, polio has been targeted
      for eradication by the year 2000 and neonatal tetanus for elimination by 1995.
      There are targeted reductions in mortality and cases of measles by the same year.
      This paper addresses the difficult issue of how optimally to integrate these
      public health initiatives into local health care practices and beliefs. At the
      workshop on Global Immunization and Culture I presented the perspective of a
      physician who has worked with the Expanded Programme on Immunization and has
      understanding at a global level of the logistics of vaccine delivery. This paper
      serves as a counterpoint to others at the workshop by raising the question of
      whether routine vaccine delivery and special eradication efforts can be best
      carried out with a uniform, technologically based approach rather than extensive
      adaptation of the program to local conditions and beliefs. The reliance on a
      largely technological approach to control of these childhood diseases which occur
      in all societies independent of social behavior is contrasted with efforts to
      control HIV infection in which social structure and practices predict the
      occurrence of disease.

PMID- 7502096
TI  - Vaccinations in the Third World: a consideration of community demand.
AB  - Impressive increases in immunization rates have been reported in several less
      developed countries (LDCs) as a result of intensive EPI programs. An issue arises
      as to whether existing rates of immunization coverage can be sustained/increased
      given projected cutbacks in funding. This issue calls into question the
      assumption that as immunizable disease rates fall, local populations will need
      less encouragement to secure immunization services. This article considers how
      immunizations are perceived by lay populations and how perceptions of utility and
      need effect demand which in turn effects the sustainability of EPI programs.
      Among issues addressed is the observation that when specific diseases are not
      linked to specific immunizations, misimpressions related to the number of
      immunizations needed for "good health" abound. Also considered are metamedical
      reasons immunizations (and immunization programs) are both resisted and demanded
      in particular political contexts.

PMID- 7502098
TI  - Enhancing coverage and sustainability of vaccination programs: an explanatory
      framework with special reference to India.
AB  - The article addresses the question in what form and under what conditions
      vaccination programs can be expected to continue once the 'take off' period is
      over. This matter is of great importance because of the need to continuously
      vaccinate new cohorts of children with a high degree of coverage and in an
      appropriate manner. Using data from India, where vaccination programs are
      integrated in regular health care delivery, an explanatory framework is presented
      which, first, analyses the vaccination program in terms of different levels,
      organizational cultures and inner-level linkages and, second, addresses the
      relation between the program and its socio-cultural context. The analysis
      provides starting points for changes that could enhance coverage and
      sustainability. Such changes include alterations in program design and
      adjustments in the views of different categories of program staff. The article
      discusses strategies directed at achieving such changes.

PMID- 7502097
TI  - Intimidation, coercion and resistance in the final stages of the South Asian
      Smallpox Eradication Campaign, 1973-1975.
AB  - This paper reviews episodes during 1973-1975 when American physician
      epidemiologists in South Asia, working under the auspices of the World Health
      Organization, intimidated local health officials and resorted to coercive methods
      in the final stages of the Smallpox Eradication Programme. While intimidation and
      coercion were successful in the short-run in ensuring disease containment, they
      evoked health-professional and popular resentments, and the long-term effect may
      have been to foster negative attitudes toward subsequent vaccination campaigns.
      At the very least these episodes suggest a need for paying attention to actual
      and perceived abuses when global health measures are introduced from 'above' into
      regional settings.

PMID- 7502099
TI  - Immunization to regulate fertility: biological and cultural frameworks.
AB  - Deliberate immunization to control fertility differs from that to control
      disease. Those differences can be discussed within various frameworks, e.g.,
      intent, recipient population, biological bases, and immunological targets. Others
      include differing perspectives of developers, providers and users, and rights of
      the state to impose programs of control. Almost all of the differences are
      grounded in the social, economic, and gendered aspects of societies. The intent
      of providing a fertility-regulating vaccine is to prevent pregnancy. In theory,
      men as well as women could receive such vaccines; in reality, most are designed
      for women. Traditional vaccines are intended to prevent disease and are generally
      given to susceptible individuals whether male or female, child or adult. The
      biological bases of contraceptive vaccines are molecules specific to
      reproduction. The immune response generated by most anti-fertility vaccines is
      directed toward 'self', one's own cells and molecules. In contrast, the bases of
      traditional vaccines are materials derived from non-self, disease-causing
      microorganisms; the immunological targets are those microorganisms or their toxic
      products. From a developer perspective vaccines that regulate fertility differ
      little from those that control disease; both prevent a particular condition.
      Developers cite these advantages to contraceptive vaccines: non-invasive, no
      serious side-effects, easy to use, reduced patient failure, and long-lasting but
      naturally reversible. Because anti-fertility vaccines have been tested only in
      small-scale clinical trials, information on user reactions and experiences is
      limited. Not surprisingly, the perspectives of women's health advocates and of
      potential users (mostly women) often differ markedly from those of developers.
      Women cite as disadvantages the cryptic nature of immunity which leaves one
      without an obvious signal for the beginning of protection (against pregnancy) and
      its decline, and the inability to 'turn-off' an immune response. Further, long
      acting contraception can complicate alleviation and side-effects, and it leaves
      women always vulnerable to sexual demands. Most women object to the lack of user
      control and are especially concerned about the enormous potential for misuse and
      coercion by population control programs should fertility-regulating vaccines
      become widely available. Many scholars and government officials subscribe to the
      following logic: the global environmental crisis is due to over-population which
      necessitates population control programs; thus pregnancy can be considered a
      disease subject to state control. But pregnancy is not a disease nor is over
      population the single major cause of environmental degradation. However, as
      governments grapple with the economic, social, and ecological consequences of
      population growth, draconian measures to control fertility will be ever more
      tempting.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7502100
TI  - Assumptions and contradictions in measles and measles immunization research: is
      measles good for something?
AB  - Measles infection, the major cause of childhood mortality among infections
      preventable by immunization, has been considered to kill mainly young and
      malnourished children. Assuming that mainly 'weak' children are saved by
      immunizations, it has been speculated that the impact on survival of immunization
      is likely to be limited because the malnourished children are more prone to die
      of other infections. However, recent studies from developing countries have
      suggested that host factors may not be the most important determinants of acute
      and long-term mortality after measles infection. Instead, it was found that
      infection contracted after exposure at home infection contracted from someone
      outside the home. Furthermore, measles is particularly severe if contracted from
      someone of the opposite sex. Hence transmission factors, in particularly
      intensity of exposure and cross-sex transmission, may be more important
      determinants of measles mortality than the determinants of measles mortality than
      the host factors usually emphasized. Consistent with these observations and in
      contrast to assumptions about 'weak' children dying, immunization is associated
      with a major reduction in mortality. Since measles immunization is associated
      with a 30% reduction in mortality or more, the impact is much larger than should
      be expected from the proportion of all deaths attributed to measles. It has
      therefore been suggested that measles immunization may prevent the persistent
      immunosuppression and delayed mortality assumed to be associated with measles.
      However, several observations contradict the common understanding that the
      function of measles immunization is only to prevent the acute and long-term
      mortality associated with measles infection. Recently, the high-titre measles
      immunization recommended by WHO was found to be associated with reduced survival
      for female recipients compared with girls who have received the standard low-dose
      measles vaccine, and this difference in survival was not due to suboptimal
      protection against measles infection. Contrary to usual assumptions. against
      measles infection. Contrary to usual assumptions, standard low-dose measles
      vaccine reduces mortality even more when given before 9 months of age, the age
      currently recommended by WHO. The beneficial impact of standard vaccine is
      apparently temporary, lasting 1 to 2 years, whereas it should increase with the
      age of the child. The beneficial effect seems to be particularly strong for
      girls. The most likely interpretation of these observations, is that standard low
      dose measles vaccine has a non-specific beneficial effect. Contrary to current
      assumptions, children who survive the acute phase of measles infection may have a
      survival advantage compared with unimmunized, uninfected children.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7502101
TI  - Socioeconomic and spatial differentials in mortality and means of committing
      suicide in New South Wales, Australia, 1985-91.
AB  - Analysis of suicide mortality in New South Wales, Australia is undertaken with
      reference to marital status and occupational status between 1986-89/90 and with
      reference to the principal means of committing suicide. Not currently married
      male manual workers were particularly at risk although marital status variations
      were significant with both genders and at different ages. Between 1985-91 male
      suicide mortality rates were significantly higher in inland non-metropolitan
      regions, especially among younger men, and were higher in inner areas of
      metropolitan Sydney. While there were no significant variations by marital status
      in the means of committing suicide there were variations between genders, and
      there were regional and social class variations in the use of guns with males.
      The use of guns was a factor in the elevated suicide mortality levels among
      inland rural youth and men, and among farmers and transport workers while the use
      of poisons was also significant with these occupational groups. The use of
      poisons was greater among persons committing suicide in the areas of elevated
      mortality in inner Sydney and the use of guns much lower.

PMID- 7502102
TI  - AIDS and injecting drug use in the United Kingdom, 1987-1993: the policy response
      and the prevention of the epidemic.
AB  - This paper assesses policy development, service changes and trends in HIV
      infection and risk behavior among injecting drug users (IDUs) in the United
      Kingdom. In 1986, the U.K. was faced with the possible rapid spread of HIV
      infection among IDUs. The combination of an outbreak of HIV infection with
      prevalence levels of 50% or more in Edinburgh, the recent diffusion of drug
      injecting, and high levels of syringe-sharing risk behaviour, suggested that HIV
      infection might spread rapidly through IDU populations. HIV prevention activities
      commenced in 1986 and developed in 1987. The first report on AIDS and Drugs
      Misuse by the Advisory Council on the Misuse of Drugs in 1988 was a major
      catalyst for change. It supported and legitimized emergent views on new ways of
      working with drug users. Between 1988 and 1993 innovative public health projects
      increased the ability to target vulnerable populations through syringe
      distribution, expansion of methadone treatment and outreach to hard-to-reach
      populations. There were major changes in service philosophy and practices, as
      ideas of harm minimization, accessibility, flexibility and multiple and
      intermediate goals were developed. There is evidence that these public health
      projects encouraged extensive changes in the health behaviour of IDUs. There have
      been major reductions in syringe-sharing risk behaviour and sharing syringes is
      no longer the norm. Evaluation of specific interventions (e.g. syringe-exchange)
      shows their importance in encouraging reductions in risk behaviour. Levels of HIV
      infection in IDUs remain low by international standards. Outside of London rates
      of about 1% have been reported; London has a low and declining prevalence of
      infection to around 7% in 1993; previous high levels in Edinburgh (55%) have
      since declined to 20%. Britain has to date avoided the rapid increase in HIV
      infection among injectors that has occurred in many parts of the world. The same
      period saw the continuation of high prevalence levels in New York and many
      European cities, and the explosive spread of HIV in many countries in south-east
      Asia. This paper acknowledges the difficulties is proving links between social
      interventions and epidemic prevention. It argues that there is prima facie
      evidence for the success of public health prevention, that the collection of
      intervention approaches in the U.K. had a significant impact on IDUs behaviour,
      and that this has helped prevent an epidemic of HIV infection among IDUs. The
      U.K. experience adds to the growing evidence of the significance of early
      interventions in encouraging behaviour change and in limiting the spread of HIV
      infection.

PMID- 7502103
TI  - Psychosocial work characteristics and cardiovascular disease risk factors in
      young adults: the CARDIA study. Coronary Artery Risk Disease in Young Adults.
AB  - The associations of high job demands, low decision latitude and job strain with
      cardiovascular disease (CVD) risk factors among 2665 black and white working men
      and women were examined in the Coronary Artery Risk Development in Young Adults
      study--a large, prospective, multi-center study of the development of CVD risk
      factors in young adults aged 18-30 years at baseline (1985-1986). Multiple linear
      and multiple logistic regression were used in cross-sectional analyses to examine
      the associations of job demands, decision latitude and job strain with blood
      pressure, total serum cholesterol, alcohol use and cigarette consumption. Inverse
      associations with risk factors were found for high job demands, low decision
      latitude and job strain. Few associations supported the hypotheses that high job
      demands, low decision latitude or job strain are associated with increased levels
      of CVD risk factors. We discuss possible explanations for these findings,
      including methodologic, age and gender differences between studies. In addition,
      we discuss the validity of job strain measures for women and minority workers.

PMID- 7502104
TI  - Nutrition, maternal responsiveness and mental development of Ethiopian children.
AB  - Forty children between the ages of 16 and 42 months and their mothers, living in
      an Ethiopian rural village, participated in the study. The objective was to
      determine the mental development of the children using the Bayley Scale of Mental
      Development, and to examine its relation to nutritional status and mother-child
      interaction. Forty-eight percent of the children were mildly or moderately
      malnourished; 7.5% severely so. The child's weight for age was significantly
      related to the child's scores on the Bayley scale. Mother-child interaction was
      assessed through a 30-60 min observation of the pair in a naturalistic setting
      around the home. The number of verbal, gestural and motor actions spontaneously
      initiated by the mother and child, as well as responses made by each to the
      others' behavior were recorded and coded separately. The rate of a mother's
      verbal responses to the child positively predicted the child's verbal score. In
      contrast, the mother's spontaneously initiated motor actions toward the child
      correlated negatively with the child's performance score. The mother's
      responsiveness was unrelated to the child's nutritional status, age or sex, but
      was best predicted by a fussing/crying child and by her expectations about the
      ages when specific social-cognitive abilities would be acquired by a child.

PMID- 7502105
TI  - Short stature as an effect of economic and social conditions in childhood.
AB  - Only a few studies on the effect of environmental factors on height are based on
      adults and none, that we could find, relates adult height to both economic and
      psycho-social conditions in childhood. The aim of this study is to investigate
      whether four indicators of economic and psycho-social conditions during childhood
      are related to a variation in adult height and whether these factors can explain
      the variation in height between men and women from different childhood classes.
      The study is based on data derived from a study of living conditions in Sweden
      conducted in 1991. Beside childhood socio-economic group, indicated by father's
      occupation, we employ four indicators of economic and psycho-social conditions
      during the childhood period, previously employed elsewhere. These are economic
      hardship, large family, dissension in the family and disunited family during
      childhood. The prevalence of short stature differs significantly by three of the
      four indicators on economic and psycho-social childhood conditions. It is also
      more common if the person has grown up in a disunited family, but this effect is
      not significant. The proportion of short persons also varied significantly by
      childhood socio-economic group. On the whole, short stature in adulthood seems to
      be a reflection of a number of adverse conditions in childhood, both economic,
      status related and psycho-social, and can, consequently, be seen as summing up
      the whole childhood period rather than merely reflecting differences in nutrition
      or any other specific condition.

PMID- 7502106
TI  - Anticipated response to three common injuries by rural and remote area residents.
AB  - Three progressively worsening injury scenarios were used to determine the
      influence of distance from medical services on the anticipated illness behaviour
      of rural and remote area residents. A total of 801 householders were interviewed
      in two rural areas of Queensland, Australia (320 in a coastal area and 481 in an
      inland area). There was a consistent trend with distance of decreasing
      willingness to seek immediate care at each injury stage. As the severity of each
      scenario increased, there was a convergence in anticipated action. Inland area
      respondents were less likely to seek medical care at each stage of the injuries
      than coastal area respondents. Distant respondents were more likely to telephone
      for medical advice before seeking care. When this was taken into account, there
      was less difference in anticipated action by distance, although those further
      from medical services still indicated a propensity to delay action in the less
      serious injuries.

PMID- 7502107
TI  - The development of a method for measuring anticipated illness behaviour in three
      common injuries.
AB  - This note outlines the rationale, development and validation of three injury
      scenarios as objective measures of anticipated illness behaviour. The measures
      were originally developed to consider differences in illness behaviour with
      distance from medical services in rural and remote areas of Queensland,
      Australia. However, the measures have a more universal applicability than the
      purpose for which they were developed. Unlike other measures of illness
      behaviour, the scenarios each incorporate a number of progressively worsening
      stages which permit the mapping of changes in individual or group behaviour. By
      working through conditions stage by stage, the likelihood of individual
      variations in interpretation of condition severity is greatly reduced and so a
      better understanding of people's responses to these conditions is obtained. In a
      survey of 800 rural households, each scenario met the proposed criteria of: (i)
      increasing urgency of action with increasing condition severity; and (ii)
      increasing agreement about urgency of action with increasing severity. The
      fractured limb scenario was perceived by respondents (in terms of urgency and
      agreement about type of action) as the most serious condition. There was little
      difference in perceived seriousness for the other two conditions.

PMID- 7502108
TI  - Pseudohypertension.
AB  - The purpose of this review is to integrate information available regarding
      pseudohypertension. A MEDLINE search (1966 to December 1993) was conducted using
      the key words pseudohypertension and Osler's maneuver. All articles containing
      reference to pseudohypertension were selected and reviewed. Additional articles
      were obtained from the citations included within these articles. Quantitative
      information from each reference was reviewed to derive qualitative statements
      about new perspectives on the pathophysiology and evaluation of
      pseudohypertension. The prevalence of pseudohypertension is unknown but probably
      increases with advancing age. Diagnosis requires a high index of suspicion.
      Demographic information has not been shown to be useful for identifying patients
      with pseudohypertension. Symptoms of postural hypotension despite
      antihypertensive therapy, treatment-resistant hypertension, and the absence of
      end-organ effects in long-standing "hypertension" are clinical features that
      suggest pseudohypertension. Automatic infrasonic blood pressure measurements may
      offer more accurate estimates of intra-arterial blood pressure than indirect
      sphygmomanometry in patients with these clinical features.

PMID- 7502109
TI  - Ectopic pregnancy: ultrasonographic diagnosis and interpretive pitfalls.
AB  - The ultrasonographic evaluation of ectopic pregnancy is fraught with potential
      pitfalls in image interpretation. Though recent advances in sonographic
      techniques have improved the precision and scope of the study, considerable
      expertise is still needed to perform and interpret the sonogram for a suspected
      ectopic gestation. In this article, we review the ultrasonic evaluation for
      ectopic pregnancy, emphasizing the difficulties in diagnosis.

PMID- 7502110
TI  - The digital toolbox for teaching.
AB  - Continued improvements in computer technology have led to significant enhancement
      of clinical teaching. We describe a "digital toolbox" consisting of personally
      accessible hardware and software products to assist in clinical teaching. The
      areas covered are computer-assisted diagnosis, digitization and display of
      clinical materials, archiving of digitized clinical materials, and decision
      analysis. All products are commercially available, and none require special
      training or customization for medical teaching application.

PMID- 7502111
TI  - Malpractice litigation fear and risk management beliefs among teaching hospital
      physicians.
AB  - We address four major issues related to physicians' fear of litigation: What are
      physicians' attitudes and beliefs toward malpractice? To whom or what do they
      attribute the "malpractice crisis"? Is fear of litigation associated with
      demographic and practice variables? What measures do physicians take to reduce
      risk? Hospital physicians in a southeastern health science center were surveyed
      (N = 356). Physicians attributed the malpractice crisis to circumstances outside
      medicine and beyond their control, perceived some patients as suitprone, and
      reported altering their practice to avoid being sued. Litigation fear was
      associated with physicians who were female, younger, not board certified, less
      clinically experienced, more clinically active, defendants in prior lawsuits, and
      in high-risk specialties. Physicians who were especially fearful of litigation
      placed less value in risk-management techniques. The findings are important in
      understanding how the prospect of litigation is perceived by physicians and how
      that perception may affect medical practice.

PMID- 7502112
TI  - Vascular and other serious infections with Mycobacterium bovis after bacillus of
      Calmette-Guerin therapy for bladder cancer.
AB  - Intravesical application of bacillus of Calmette-Guerin (BCG) has proved to be an
      effective form of treatment for some stages of bladder cancer. Infrequent,
      serious complications of this treatment have become apparent as its use has
      become more widespread. We report a case of Mycobacterium bovis mycotic abdominal
      aortic aneurysm and a case of M. bovis mycobacteremia that developed as
      complications of intravesical BCG therapy. These cases are discussed in the
      context of a review of reported complications of intravesical BCG therapy and a
      review of measures currently advocated to prevent them.

PMID- 7502113
TI  - An evaluation of the safety and efficacy of fluconazole in the treatment of
      onychomycosis.
AB  - Sixteen subjects were enrolled in this open-label noncomparative study to
      evaluate the safety and efficacy of fluconazole as a single daily dose for a
      period of 6 months. Liver function enzymes were monitored to assess safety. An
      adverse function questionnaire was used on a monthly basis to assess patient
      tolerance. A visual analogue scale was used to assess efficacy of treatment.
      After 6 months of fluconazole, all subjects experienced improvement in the
      appearance of their nails. None of the subjects evidenced any elevation in liver
      function enzymes. Adverse reactions were limited and consistent with other
      studies involving fluconazole. Fluconazole proved to be safe and efficacious in
      the treatment of onychomycosis. Further studies are needed to determine a cost
      effective dosing regimen for the treatment of onychomycosis with fluconazole.

PMID- 7502114
TI  - Late generalized tuberculosis: unusual features of an often overlooked disease.
AB  - Late generalized tuberculosis--ie, disseminated tuberculosis occurring long after
      the primary infection-- is an often unrecognized cause of severe illness in
      patients with relative immunocompromise, such as the elderly, alcoholics, or
      those with chronic illnesses. It has become increasingly recognized in the
      elderly as a cause of a gradual debilitating illness, often with vague
      constitutional symptoms. We describe three cases of late generalized tuberculosis
      in patients seen on a single medical service over a 6-month period. Each case
      presents a unique features of extrapulmonary tuberculosis that escaped diagnosis
      for some time, and each of these elderly patients had a protracted and wasting
      illness. We present these cases and the ensuing discussion to reemphasize to
      clinicians that late generalized tuberculosis may be experiencing increased
      prevalence among the elderly and that diagnosis requires a heightened suspicion.
      A history of past tuberculosis infection is not always present, but the diagnosis
      should be entertained in any elderly patient with a chronic debilitating illness.

PMID- 7502115
TI  - Evaluation of the psychosocial impact of the MiniMed variable-rate implantable
      insulin pump.
AB  - We examined the psychosocial impact of treatment with an implantable insulin pump
      among persons with insulin-dependent diabetes mellitus (IDDM). Of specific
      interest was whether use of the MiniMed implantable insulin pump (MIP) resulted
      in changes in functional status, performance of diabetes self-care behavior,
      psychologic symptoms, and perceived level of stress. From a sample of 36 patients
      with IDDM, 10 persons were randomly selected to receive the MIP, while the
      remaining 26 served as control subjects. Additionally, a nonrandom sample of
      three MIP recipients from an additional site were included in the MIP group. At
      regular assessment intervals, all participants completed self-report
      questionnaires regarding psychosocial functioning and monitored blood glucose
      levels. After 4 months of MIP use, MIP recipients did not significantly differ
      from control subjects on any measure of psychosocial functioning; however, MIP
      use did have an impact on diabetes self-care. The MIP users monitored their blood
      glucose levels more frequently and had lower average blood glucose levels than
      control subjects. Additional follow-up is needed to determine the long-term
      psychosocial impact of implantable insulin pump therapy.

PMID- 7502116
TI  - Herpetic geometric glossitis: a distinctive pattern of lingual herpes simplex
      virus infection.
AB  - Two immunocompromised patients with herpetic geometric glossitis, a clinically
      distinctive form of lingual herpes simplex virus (HSV) type 1 infection, are
      described. The significant features of herpetic geometric glossitis are
      summarized, the clinical differential diagnosis of this form of HSV infection is
      reviewed, and the possible pathogenesis of these lingual lesions is discussed.
      Both of our patients, as well as all previously described patients with this
      condition, had extremely painful cross-hatched, branched, and/or linear fissures
      on the dorsal aspect of the tongue. Symptoms promptly resolved within 1 to 2
      days, and the fissures subsequently healed within 3 to 12 days after systemic
      acyclovir therapy was initiated. In contrast to tongue lesions of herpetic
      geometric glossitis, similar-appearing lingual lesions of other conditions are
      usually asymptomatic. The similar morphology of corneal dendrites in herpetic
      epithelial keratitis and linear fissures in herpetic geometric glossitis suggest
      the possibility that these HSV mucosal lesions may have a common pathogenesis.

PMID- 7502117
TI  - Pica in a rural obstetric population.
AB  - The incidence of pica during pregnancy has been reported to range from 0% to 68%
      depending on the patient population. This study was designed to define
      characteristics and factors influencing the practice of pica in a rural obstetric
      population. Our study group was 125 consecutive pregnant women who were
      interviewed at their initial antenatal visit about attitudes and behavior
      regarding pica practices. The prevalence of anemia was determined. Chi-square and
      t tests were used when appropriate. A pica was found in 18 (14.4%) patients.
      There were no significant differences between patients with a pica and those with
      none with respect to age, race, weight, or anemia. Substances ingested included
      white and red dirt, ice, cornstarch, laundry starch, soap, ashes, chalk, paint,
      and burnt-matches. Characteristics of patients with pica included cravings (6 of
      18 or 33.3%), pica before pregnancy (10 of 18 or 56.6%), childhood pica (6 of 18
      or 33.3%), and the presence of other household members with pica (56.6%). Our
      study data suggest that pica is frequently associated with similar practices
      during childhood and nonpregnant states. These patients also may be at risk for
      lead toxicity or other environmental toxin exposures.

PMID- 7502118
TI  - Are learning objectives useful in evaluating medical school course and instructor
      performance?
AB  - We tested the hypothesis that learning objectives could be used to evaluate
      course and instructor effectiveness. Ninety-seven third-year medical students who
      had their surgical clerkship or their medical clerkship as their first clinical
      rotation were compared. The surgery clerks received 171 urologic learning
      objectives. Students taking the surgical clerkship had significantly higher
      postclerkship recognition of the learning objectives than did medical clerkship
      students. One year later, these students were again surveyed to determine whether
      they still knew the correct response to the learning objective. The follow-up
      survey showed that 50% of the students recognized objectives covered in five of
      the eight urology lectures, while the other lectures were not effective. Students
      who recognized the objective on the postclerkship evaluation were more likely to
      think the objective had been taught on this follow-up survey. These data suggest
      that learning objectives are useful for evaluating course and instructor
      effectiveness.

PMID- 7502119
TI  - Physician religious beliefs and the physician-patient relationship: a study of
      devout physicians.
AB  - The purpose of this study was to determine the type and frequency of religious
      interactions that occur between devout physicians and their patients. Physicians
      identified by their peers as having religious or spiritual beliefs that were an
      important part of their lives were surveyed. Forty physicians responded (response
      rate 77%). In general, these physicians agreed that their religious beliefs have
      an important influence on their practice of medicine. Thirty-two percent reported
      having shared their beliefs with patients. Praying aloud with patients occurred
      with only 13% of patients, but 67% of respondents reported having done this on at
      least one occasion. Multivariate analysis showed the physician's religious group
      to be the most important determinant of sharing beliefs with patients, occurring
      most commonly with Protestant physicians. In this small sample of devout
      physicians, physician religious beliefs appear to influence the interactions
      between physicians and their patients.

PMID- 7502120
TI  - Detection of specific antibodies in human blastomycosis by enzyme immunoassay.
AB  - Serologic tests for the diagnosis of blastomycosis have had inadequate
      sensitivity, but results are improved with enzyme immunoassay (EIA) with A
      antigen of Blastomyces dermatitidis. The Premier Blastomyces EIA kit (Meridian
      Diagnostics Inc, Cincinnati, Ohio) detected antibody against the B dermatitidis A
      antigen in sera from 104 of 125 patients (83%) with culture-proven blastomycosis.
      Semiquantitative index values (positivity multiplied by the dilution) ranged from
      1.0 to 423.3; the degree of positivity correlated with disease activity.
      Immunodiffusion bands were infrequently detected, with positive specimens from
      only 19 (21%) of 92 patients with blastomycosis. In 8 of 24 patients with
      histoplasmosis, 24 of 51 specimens (47%) were positive for Blastomyces antibody
      by EIA; index values were lower, with a mean of 3.8 versus 24.3 for sera from
      patients with blastomycosis. Only 1 of 13 patients with other fungal infections
      had positive results with EIA. This EIA system provided better sensitivity than
      previously available commercial systems for serodiagnosis of blastomycosis.

PMID- 7502121
TI  - Splenic lymphoma with villous lymphocytes: diagnosis by flow cytometry and
      immunocytochemistry.
AB  - Splenic lymphoma with villous lymphocytes (SLVL) is a recently described low
      grade non-Hodgkin's lymphoma that may be confused with chronic lymphocytic
      leukemia and hairy cell leukemia. Herein we report a case of SLVL and show how
      clinical features, cellular morphology, and flow cytometric analysis are used to
      distinguish among these three disorders. A newly developed immunocytochemical
      technique that allows detection of tartrate-resistant acid phosphatase on
      formalin-fixed, paraffin-embedded specimens was useful in refining our diagnosis
      of SLVL. Establishing the precise diagnosis is important because treatment is
      different for each of the three chronic lymphoproliferative malignancies.

PMID- 7502122
TI  - Diagnosis of probable cocaine-induced cerebral vasculitis by magnetic resonance
      angiography.
AB  - Cocaine-induced cerebral vasculitis is a serious but uncommon clinical entity. We
      present a case of probable cocaine-induced vasculitis that was unusual in that it
      was suggested by magnetic resonance angiography. The patient was a 42-year-old
      woman, who used cocaine both intravenously and intranasally, who was admitted
      with the acute onset of an illness that resembled bacterial meningitis. Results
      of the initial standard evaluation were negative, and a diagnosis of cerebral
      vasculitis was ultimately suggested by magnetic resonance angiography. We believe
      this to be the first reported case of the diagnosis of cocaine-induced cerebral
      vasculitis to be suggested by magnetic resonance angiography.

PMID- 7502123
TI  - Desmoplastic fibroma: a role for radiotherapy?
AB  - Desmoplastic fibroma is a rare, locally aggressive, benign tumor that is
      considered the skeletal counterpart of the desmoid tumor of soft tissues.
      Although the treatment of choice of desmoplastic fibroma is surgical excision,
      radiation therapy should be considered when surgery is not a viable option.

PMID- 7502124
TI  - Diaphragmatic myoclonus: diagnosis by fluoroscopy and electromyography with
      response to phenytoin.
AB  - A 40-year-old woman presented a 6-week history of "fluttering" in her chest. A
      diagnosis of bilateral diaphragmatic myoclonus was made by fluoroscopy and
      electromyography of both hemidiaphragms. No central or peripheral cause was
      identified, but treatment with intravenous phenytoin had an immediate effect.
      With therapy, she has been symptom free for 12 months.

PMID- 7502125
TI  - Malignant teratoma of the testicle: diagnosis suggested by preoperative
      ultrasonography.
AB  - A 22-year-old white man was found to have malignant teratoma of the testicle
      (nonseminomatous germ cell testicular tumor), which had been suggested by
      ultrasonography. Modified template retroperitoneal lymphadenectomy with nerve
      sparing showed no microscopic metastatic tumor.

PMID- 7502126
TI  - Rationing health care.

PMID- 7502127
TI  - Rectal examinations and appendicitis malpractice claims.

PMID- 7502128
TI  - Raynaud's phenomenon and anorexia nervosa.

PMID- 7502129
TI  - Challenges of the spine specialists. North American Spine Society Presidential
      Address. Minneapolis, Minnesota, October 1994.

PMID- 7502130
TI  - My first 80 years. NASS presidential guest speaker address.

PMID- 7502131
TI  - The pars defect as a pain source. A histologic study.
AB  - STUDY DESIGN: Tissue from the pars defects of six adult patients with symptomatic
      spondylolysis and spondylolisthesis was obtained at surgery. A histologic study
      was conducted to identify and characterize neural elements in this tissue.
      OBJECTIVES: To determine if nociceptive nerve endings were present within the
      pars defect of patients with symptomatic spondylolysis. SUMMARY OF BACKGROUND
      DATA: The origin of back pain in patients with spondylolysis remains uncertain.
      The defect in the pars interarticularis has been implicated as a possible pain
      source. METHODS: The soft tissue from the pars defect was obtained at surgery. A
      modified gold chloride stain was used to prepare the tissue for histologic
      examination. Tissue blocks were sectioned and studied under light microscopy.
      RESULTS: Neural elements were found in all specimens examined. Free nerve endings
      believed to have nociceptive function were identified in all specimens. The
      density of neural elements varied between specimens. CONCLUSIONS: The finding of
      neural elements, including free nerve endings within the pars defect tissue,
      suggests that the pars defect may be a source of back pain in some patients with
      symptomatic spondylolysis.

PMID- 7502132
TI  - An evaluation of motor-evoked potentials for detection of neurologic injury with
      correction of an experimental scoliosis.
AB  - STUDY DESIGN: Controlled correction of scoliosis in a rat model was used to
      assess the accuracy of intraoperative motor-evoked potential monitoring.
      OBJECTIVES: The purpose of this study was to develop a model in which motor
      evoked potential changes could be compared with neurologic function after
      surgery, such that a threshold for responding to motor-evoked potential changes
      may be established. SUMMARY OF BACKGROUND DATA: Intraoperative motor-evoked
      potential monitoring has become technically feasible. Clinical application now
      depends on the development of useful interpretation parameters and correlation
      with neurologic sequelae. METHODS: Experimental scoliosis was produced in 30 rat
      pups. After growth, the rats underwent correction of their scoliosis by
      distraction. Changes in tcMMEP onset latency and amplitude were measured.
      Distraction was applied either until a 10% delay in tcMMEP onset latency (Group
      1), until tcMMEP responses were ablated (Group 2), or for 10 minutes after the
      loss of transcranial magnetic stimulation response (Group 3). RESULTS: In Group 1
      (n = 10), all animals had tcMMEP with normal onset latency and normal neurologic
      examinations 24 hours after surgery. In Group 2 (n = 10), tcMMEP were normal in
      four rats, markedly delayed in three rats, and absent in three rats 24 hours
      after surgery. neurologic examination was normal in the four rats with normal
      tcMMEP. Moderate deficit was noted in two of the three rats with prolonged onset
      latency 24 hours after surgery; the third was intact. Moderate neurologic injury
      was noted in two of three rats with absent tcMMEP 24 hours after surgery; the
      third rat was paralyzed. In Group 3 (n = 10), vertebral dislocation was noted on
      lateral radiographs in eight of 10 animals. Twenty-four hours after surgery,
      tcMMEP remained absent, and paralysis was noted in the eight rats with
      dislocation. The two rats without dislocation had delayed tcMMEP but some return
      of neurologic function. CONCLUSIONS: Comparison of the three groups shows a
      significant correlation between tcMMEP and endpoint neurologic outcome. None of
      the rats in Group 1 had a neurologic deficit after surgery as opposed to five of
      10 rats in Group 2 and 10 of 10 rats in Group 3 with significant neurologic
      injury. These findings suggest that a 10% delay in onset latency would be an
      appropriate threshold for responsing to changes in tcMMEP.

PMID- 7502133
TI  - Can we distinguish between benign versus malignant compression fractures of the
      spine by magnetic resonance imaging?
AB  - STUDY DESIGN: The authors investigate the usefulness of magnetic resonance
      imaging in differentiating benign versus malignant compression fractures by
      reviewing patients and a fracture model in a canine model. OBJECTIVES: To
      determine the sensitivity and specificity of magnetic resonance imaging in
      differentiating benign versus malignant compression fractures of the spine and to
      obtain distinguishing features in magnetic resonance imaging. SUMMARY OF
      BACKGROUND DATA: The differentiation between benign and abnormal compression
      fractures of the thoracolumbar spine has important implications regarding patient
      treatment and prognosis. Plain radiographs, bone scans, and computed tomography
      are not accurate imaging modalities for this purpose. METHODS: Magnetic resonance
      imaging scans of 22 patients with confirmed lesions of the thoracolumbar spine
      were studied. There were 11 malignant and 11 benign lesions. Two experienced
      neuroradiologists blindly reviewed the magnetic resonance imaging scans and
      determined benign or malignant lesions. A canine study was performed to simulate
      a compression fracture model with a vertebral osteotomy in two dogs, and serial
      contrast-enhanced magnetic resonance imaging scans were performed 15, 30, 60 and
      90 days after surgery. RESULTS: The correct interpretation between two
      neuroradiologists was 77% and 95%. The combined sensitivity rate was 88.5%, and
      the specificity rate was 89.5%. Magnetic resonance imaging reliably distinguished
      benign versus malignant lesions based on the anatomic distribution and intensity
      of signal changes of bone and adjacent tissues, contrast enhancement
      characteristics, and changes over time. Only one malignant lesion was
      misinterpreted by both neuroradiologists as benign, whereas there was one
      additional missed malignant lesion and three misinterpreted benign lesions by one
      radiologist. In the canine study, signal changes and enhancement were found 60
      days after surgery, but no signal changes or enhancement were noted on the scan
      90 days after surgery. CONCLUSIONS: Magnetic resonance imaging scans can detect
      malignant vertebral lesions early, but acute healing compression fractures may
      mimic the findings of metastatic lesions. The use of contrast-enhanced magnetic
      resonance imaging scans and serial magnetic resonance imagings are helpful for
      additional differentiation between benign and malignant compression fractures. In
      addition to magnetic resonance imaging scans, other diagnostic tests and clinical
      findings should be correlated before biopsy or surgery of the suspected lesion.

PMID- 7502134
TI  - Administrative databases' complication coding in anterior spinal fusion
      procedures. What does it mean?
AB  - STUDY DESIGN: A review of a cohort of 310 consecutive patients who underwent
      anterior spinal fusion was performed to evaluate the accuracy of hospital ICD-9
      CM complication coding. OBJECTIVES: To better understand the clinical
      significance of conclusions suggested by studies that rely on electronic
      administrative databases for their data source. SUMMARY OF BACKGROUND DATA:
      Despite their availability, there have been no studies to date that have
      evaluated the accuracy of ICD-9-CM administrative databases as they relate to the
      actual clinical experience in spinal procedures. METHODS: A physician and a
      research technician independently reviewed the primary medical records for the
      occurrence of complications. This data was compared with the hospital-acquired
      ICD-9-CM coded complications. RESULTS: The physician reviewer identified 152
      complications in 119 patients, with 32 different types of complications. The
      research abstracter identified 175 complications in 130 patients, with 34
      different types of complications identified. Hospital ICD-9-CM coding identified
      105 complications in 80 patients, including only 11 different ICD-9-CM codes.
      Overall, 27% of ICD-9-CM complication codes were listed as "unspecified or
      unclassified complications, reactions, or misadventures," and contained no
      meaningful clinical information. Cardiac and pulmonary complications were over
      estimated and wound infections and genitourinary and gastrointestinal
      complications were underestimated by ICD-9-CM coding. CONCLUSIONS: Studies of
      complications of spinal procedures using data derived from hospital ICD-9-CM
      complication codes may be intrinsically flawed because the data available to
      researchers from these electronic databases may be inaccurate.

PMID- 7502135
TI  - Instrumentation of the cervicothoracic junction after destabilization.
AB  - STUDY DESIGN: The biomechanics of three different instrumentation constructs
      applied at the destabilized cervicothoracic junction were evaluated. OBJECTIVES:
      To find an efficient way in restoring stability of the cervicothoracic junction
      in cases with and without laminectomy. SUMMARY OF BACKGROUND DATA: Different
      instrumentation techniques have been evaluated biomechanically and used
      clinically for managing instabilities between the fourth and sixth cervical
      vertebrae. These constructs have not been evaluated at the cervicothoracic
      junction. METHODS: Six human spines were tested nondestructively in axial
      torsion, flexion, and extension with the C6-T2 motion segments left
      unconstrained. The three-dimensional displacements and rotations between C7 and
      T1 vertebrae were measured using a sonic digitizer. After intact testing, a
      distractive-flexion Stage 3 cervical spinal injury was simulated surgically
      between C7 and T1. The specimens underwent sequential instrumentation and
      mechanical testing with three constructs: posterior Synthes lateral mass plate,
      posterior pediatric Cotrel-Dubousset rod system with lamina hooks and a
      crosslink, and anterior Synthes cervical locking plate. RESULTS: Posterior
      stabilization techniques had statistically more stiffness than anterior plates.
      The Cotrel-Dubousset system offered the largest stiffness ratio
      (instrumented/intact) in flexion, extension, and rotation. There was no
      statistical difference between posterior plates and Cotrel-Dubousset
      instrumentation. The stiffness of the anterior plate did not differ significantly
      from the intact spine. CONCLUSION: Our data show that instability of the
      cervicothoracic junction can be efficiently restored by either anterior plates,
      posterior plates, or posterior hook-rod constructs (Cotrel-Dubousset). Posterior
      constructs showed increased stiffness over anterior plates.

PMID- 7502136
TI  - The effect of interposition membrane on the outcome of lumbar laminectomy and
      discectomy.
AB  - STUDY DESIGN: This study evaluated clinical and magnetic resonance imaging
      differences of patients treated surgically for lumbar disc herniation. Clinical
      follow-up and magnetic resonance imaging evaluation of epidural fibrosis were
      used to assess patient outcome. OBJECTIVES: The purpose of this study was to
      evaluate the difference in clinical outcome with either free-fat graft, Gelfoam,
      or no interposition membrane placed in the laminectomy defect after nerve root
      decompression. SUMMARY OF BACKGROUND DATA: Epidural fibrosis has been considered
      a cause of recurrent symptoms after lumbar laminectomy, and numerous materials
      have been evaluated for prophylaxis of the "laminectomy membrane." These have
      been mainly histologic and animal studies with no data correlating clinical
      symptoms and postoperative epidural scar formation. METHODS: One hundred fifty
      six patients who were treated surgically for lumbar disc herniation were randomly
      assigned to one of three groups and followed prospectively for at least 1 year.
      Thirty-three of these patients were received magnetic resonance imaging
      evaluations after 6 months by an independent radiologist who graded the amount of
      epidural scar formation. The patients were assessed at 1 year and given a rating
      of excellent, good, fair, or poor, and the scar was graded as none, minimal, or
      moderate. RESULTS: Although 97% of all patients improved, 83% were rated
      excellent or good. There were no statistical differences between the three groups
      clinically and radiographically. Patients with workers compensation had a
      statistically significant lower success rate (P < 0.001). CONCLUSIONS: Clinical
      outcome after lumbar disc surgery does not correlate with the use or type of
      interposition membrane used to prevent epidural fibrosis.

PMID- 7502138
TI  - Neural mechanisms of lumbar pain.
AB  - This article discusses neuroanatomic and neurophysiologic bases for low back
      pain. Evidence for the existence of pain generators in facet, disc, muscle, nerve
      roots, and dorsal root ganglia are discussed. Mechanisms that may explain the
      persistence of pain, including neurogenic and non-neurogenic inflammation and
      central sensitization, are also presented.

PMID- 7502137
TI  - Laparoscopic discectomy with anterior lumbar interbody fusion. A preliminary
      review.
AB  - STUDY DESIGN: Patients presenting with L5-S1 anterior column disease with or
      without herniation into the spinal canal but without stenosis underwent magnetic
      resonance imaging screening before surgery to determine surgical suitability for
      laparoscopic anterior lumbar interbody fusion relative to the aortic bifurcation
      and approach to the disc space. OBJECTIVES: To analyze and evaluate the
      laparoscopic approach, technique, and benefit of anterior lumbar discectomy and
      interbody fusion by distraction and compression-loading of autograft only as
      compared with cage-spacer-enhanced autograft fusion. SUMMARY OF BACKGROUND DATA:
      Advancement in minimally invasive spine surgery techniques has provided options
      with less morbidity for posterior lumbar procedures. General surgical
      advancements in laparoscopy and advantages of traditional anterior lumbar
      interbody fusion, including restoration of disc height and exposure for safe
      nerve decompression, provided a basis for an integrated procedure that would
      address anterior column abnormality with low surgical morbidity. METHODS: Five
      patients underwent technically successful laparoscopic anterior lumbar interbody
      fusion with approach to the disc space by an experienced laparoscopic general
      surgeon. A sixth patient in the study group was unable to undergo laparoscopic
      fusion because of an iliac vein tear during the surgical approach. After the
      approach, a spine surgeon followed with complete manual discectomy and interbody
      autogenous fusion laparoscopically. Two to three Cloward-type dowels were
      obtained by separate incision from the anterior iliac crest. RESULTS: All
      patients by 6-month follow-up examination were clinically fused with no motion on
      flexion-extension radiographs. One patient had slight anterior retropulsion of
      one dowel without the necessity of reoperation. CONCLUSIONS: Laparoscopic L5-S1
      anterior lumbar interbody arthrodesis may represent a viable option for patients
      with abnormality, including anterior column and degenerative disc disease.

PMID- 7502139
TI  - Spinal nerve root compression.
AB  - The pathophysiology of sciatica is not completely understood, although our
      understanding of its causes is increasing. Mechanical alterations combined with
      inflammatory changes lead to pain. Compression alters nerve root conduction and
      compromises the nutritional support of spinal nerve roots (through intrinsic and
      extrinsic vascularity and cerebral spinal fluid percolation). Mechanical forces
      can lead to intraneural damage and functional changes in nerve roots. Chemical
      and metabolic effects can create an inflammatory response. Varying causes of
      inflammation coupled with varying degrees of compression can occur anywhere along
      the cauda equina or spinal nerve root, including the dorsal root ganglia, and
      contribute to the pain response and neurologic deficits associated with sciatica.

PMID- 7502140
TI  - The role of inflammation in lumbar pain.
AB  - The clinical features of many cases of low back pain is inadequately explained by
      anatomic abnormalities alone. A pathophysiologic mechanism that includes a
      combination of mechanical and biochemical factors is an alternative explanation
      that is accompanied by less paradox than a purely structural paradigm. A
      potential unifying feature includes inflammation of neural elements caused by the
      chemical components of the intervertebral disc. There is a historical basis to
      the concept of an immunologic potential of the lumbar disc. No discrete in situ
      evidence or discrete mechanism has been previously identified. The recent
      demonstration of immunohistopathologic evidence of an immunocompetent cellular
      response at the epidural interface of lumbar HNPs supports the concept of the
      immunogenic capacity of nucleus pulposus. The identification of high levels of an
      inflammatory enzyme, phospholipase A2, in lumbar herniated and degenerative discs
      presents the basis for a direct inflammogenic capability of lumbar discs,
      separate from a immunologic mechanism. Subsequent experimental findings of
      conduction block and perineural inflammation as a consequence of extrathecal
      application of autologous nucleus pulposus and axonal injury after animal nerve
      injection of the human disc phospholipase A2 further validates this concept.
      There is a strong theoretic basis to support the concept that the clinical
      features of many lumbar disc patients may be explained by inflammation caused by
      biochemical factors alone or combined with mechanical deformation of lumbar
      tissues, rather than mechanical factors alone.

PMID- 7502141
TI  - Open discectomy as treatment for herniated nucleus pulposus of the lumbar spine.
AB  - Open discectomy is the "gold standard" for operative intervention in patients
      with herniated lumbar discs whose conservative treatment has failed. Over 60
      years the indications for surgery and the expected success rates have been
      clearly elucidated. The specific patient selection and determination of surgical
      procedures continues to evolve. Recurrent herniations occur at a low rate, and
      serious complications are rare.

PMID- 7502142
TI  - Magnetic resonance imaging. Use in patients with low back or radicular pain.
AB  - With the current emphasis on cost containment, it is important to order the
      single best diagnostic test when clinical uncertainties must be resolved.
      Magnetic resonance imaging is currently the optimal imaging modality to provide
      the maximum amount of information when evaluating patients with suspected spinal
      disorders. A comprehensive magnetic resonance imaging study is needed along with
      a subspecialty interpretation to provide the greatest amount of useful clinical
      information.

PMID- 7502143
TI  - Radiographic assessment for patients with low back pain.
AB  - Guidelines for radiographs of the lumbar spine are established. In general,
      radiographs are not believed to be necessary for a first episode of low back pain
      present for less than 7 weeks. Exceptions to this include various medical or
      physical findings, which are listed. In general, anteroposterior and lateral
      views only should be done initially. Indications for other views are discussed.

PMID- 7502144
TI  - Contemporary concepts in spine care. Epidural steroid injections.
AB  - Epidural steroid injections are commonly used for the management of lumbosacral
      radicular syndromes. The literature is replete with case reports and
      noncontrolled studies, but relatively few controlled studies exist. The well
      designed studies that are available, however, do show a significantly positive
      pain reducing benefit from lumbar epidural steroid injections. This Contemporary
      Concepts review summarizes theoretic concepts, clinical applications, and data
      from the literature regarding the use of lumbar epidural steroid injections and
      provides current recommendations and suggestions for future research.

PMID- 7502145
TI  - The effect of lumbar belts on isolated lumbar muscle.

PMID- 7502146
TI  - Complications after transpedicular stabilization of the spine.

PMID- 7502147
TI  - Repair of vertebral artery injury during anterior decompression.

PMID- 7502148
TI  - [From knowledge to action and vice versa. Topics and dilemmas of public health].

PMID- 7502149
TI  - [Mexico: reproductive behavior and social margination, 1970-1990. Elements of
      geographic diagnosis in reproductive health].
AB  - The lack of a definite knowledge on regional reproductive behavior
      characteristics hinders the evaluation of the goals stated in the General
      Population Law (Ley General de Poblacion) and counteracts any efforts towards
      equating population growth with regional development. The present work aims at
      overcoming this problem. Indirect specific fertility rates and global fertility
      rates (GFR) were obtained by state, using census and vital statistics data for
      the states of Mexico during the 1970-1990 period. Reproductive behavior was
      related to social deprivation indexes used by PRONASOL and CONAPO for those
      years. A high statistically significant correlation (p < 0.01) between state
      social deprivation levels and the downward trends of GFR for the same decades was
      found. Findings evidence a general downward trend of GFR during the period of
      study. However, this trend was not uniform across the country. Further studies
      are needed to determine whether these differences are due to the various social
      deprivation levels rather than to the effectiveness and extension of family
      planning programs. Mapping these results could be useful as diagnostic elements
      of the reproductive behavior of the population and also generates information
      necessary to support social organized responses in reproductive health.

PMID- 7502150
TI  - [Poverty in Mexico. I. Methodology and evolution].
AB  - This article is the first of two parts of a research report on the evolution and
      magnitude of poverty in Mexico. Herein are presented the methodologies used in
      both parts and the evolution of poverty. The Poverty Line methodology (PL), in
      its Standard Basket of Essential Satisfiers version, is succinctly explained. Two
      problems on the definition of normative requirements are emphasized: the
      foundations of such requirements and the access route by which needs are to be
      met (private consumption or public transfers). Identification of six household
      welfare sources allows for criticism of PL and Unsatisfied Basic Needs
      methodologies which the Integrated Poverty Measurement Method (IPMM) brings
      together. IPMM is used to estimate the magnitude of poverty in 1989. The results
      are presented in the second part of this report. Results analyzed in the last
      section of this article show that while poverty in Mexico decreased steadily from
      77.5% in 1963 to 48.5% in 1981, it increased since 1982, reaching 66% in 1992.

PMID- 7502152
TI  - [Visual contrast sensitivity in healthy Mexican population].
AB  - This paper presents a descriptive study of visual contrast sensitivity on 224
      healthy Mexican individuals. Central tendency measures, Student's t test, as well
      as simple frequencies were the statistical tests used for data analysis. A format
      to evaluate visual contrast sensitivity adequate to healthy Mexican population is
      proposed, taking into account that the normal visual contrast sensitivity curve
      of Mexicans was found to be lower than the international standards.

PMID- 7502151
TI  - [Poverty in Mexico. II. Magnitude].
AB  - This is the second part of a research report on the evolution and magnitude of
      poverty in Mexico. Application of the Integrated Poverty Measurement Method,
      explained in the first part of this report, shows a poverty headcount ratio (H)
      of 70.6% and an extreme poverty H of 44.7%. H turns out higher by the UBN
      (Unsatisfied Basic Needs) method than by the PLT (Poverty Line plus working time)
      approach. The poverty gap or poverty intensity (I), is for all poor 0.44 but
      reaches 0.58 for the extremely poor. Both H and I are substantially higher in the
      rural than in the urban areas. UBN poverty gap is bigger than the PLT gap. When
      UBN is disaggregated into its components, deprivation turns out the highest in
      health care and social security. Degree of poverty calculations (HI), the product
      of H and I, which constitute a good basis for anti-poverty expenditures
      allocation, show that despite the fact that a larger number of poor persons live
      in the urban areas, the number of equivalent poor people is higher in the rural
      areas.

PMID- 7502153
TI  - [Autonomous National University of Mexico (UNAM) medical students' attitudes to
      research and learning: 1984-1994].
AB  - This study evaluates, after a 10-year period, the attitudes of medical students
      towards research and learning at the National University of Mexico (UNAM), and
      tries to determine the role that experiences obtained during academic years could
      play in orienting these attitudes. Results indicate that all four groups of
      participant students,--1st and 4th-5th grades, in 1984 and in 1994--show slightly
      positive attitudes towards research and learning. No significant attitude changes
      were observed after the 10-year period in students who enter medical school nor
      in those who begin clinical practice. Besides, it was found a significant
      correlation between these two attitudinal factors. Some possible explanations for
      these results are discussed, as well as some steps that could help to promote
      positive attitudes towards research and learning.

PMID- 7502154
TI  - [Soft drink consumption patterns in a Mexican population].
AB  - To evaluate soft drink consumption patterns in the Mexican population, the
      authors conducted a survey among people over 10 years of age in Mexico City
      (september-october 1993). Also, pH levels of commonly available beverages were
      measured using standard laboratory techniques. Results indicated that each one of
      the 33 soft drink brands and 15 brands of juices and beverages available, had
      markedly acidic pH values (between 2.46 and 3.96). Out of the 2,008 respondents
      (55.3% male, 44.7% female; response rate, 90.1%), 1,657 (82.5%) admitted drinking
      soft drinks daily, while 351 (17.5%) said they did not drink this type of
      beverages. Even though high consumption was frequent in all age groups, self
      reported consumption was partially associated to age, being higher in the younger
      groups. The mean number of soft drinks ingested per day was reported to be 1.7,
      SD 1.3, and 9.3 per week SD 9.9. Self-reported consumption appeared to be
      independent of schooling level. Even though the largest proportion of non
      consumers was found in the group that considered soft drinks to be a very
      important contributing factor to caries development, most interviewees agreed
      that soft drinks consumption was an important cariogenic factor. This attributed
      role was more prominent among interviewees with a higher level of schooling.

PMID- 7502155
TI  - [The logic of a traditional health belief: solar eclipse and pregnancy in
      Ocuituco, Mexico].
AB  - An analysis of the logic of one of the commonest health beliefs in rural areas of
      Mexico is made, taking as a starting point testimonies collected in the area of
      Ocuituco, in the state of Morelos. This belief suggests that a pregnant woman is
      in danger of having a harelipped baby during a solar eclipse. The importance of
      the knowledge about the logic of this kind of beliefs is discussed from a public
      health perspective. These beliefs are associated with specific forms of suffering
      and give way to particular preventive measures which must be taken into account
      if the efficacy of health programs is to be increased. The interrelation of these
      beliefs with other traditional elements (such as the "loss of the shadow" and the
      "hot-cold theory") is discussed. Also, some of the already existing
      interpretations of this belief which seek to link the "loss of the shadow" with
      the solar eclipse belief are reviewed. Finally, an alternative interpretation of
      this belief is made from a structuralist methodological perspective. This
      interpretation is grounded in the Nahuatl myth on the creation of the sun and the
      moon, and in an analysis of the nature of rabbits in the Nahuatl culture,
      according to historic secondary sources. It is suggested that the belief about
      the danger of a solar eclipse must be interpreted in connection to the "hot-cold
      theory", but not to the "loss of the shadow". This paper concludes by emphasizing
      the importance of this type of research within the public health field, as it
      enables us both to understand the underlying logic of this type of conceptions,
      and to reinforce the dialogue between modern and alternative medicine, so that
      the daily encounter between these two types of medicine can be facilitated.

PMID- 7502156
TI  - [Beliefs about chili pepper consumption and health in Mexico City].
AB  - Eating chili peppers is a cultural tradition in Mexico. Controversial
      characteristics have been empirically associated to chili pepper consumption and
      human health. In this paper, the beliefs about the health impacts of chili pepper
      consumption in two independent groups of Mexico City residents are described. The
      results confirm, on the one hand, that there is a wide variety of health benefits
      and damages associated with chili pepper consumption, but on the other hand, that
      the levels of chili pepper consumption are not related to beliefs about its human
      health impact.

PMID- 7502157
TI  - [Molecular bases of cancer immunology].
AB  - The immune system is a tight network of different types of cells and molecules.
      The coordinated action of these elements mounts a precise immune response against
      tumor cells. However, these cells present several escape mechanisms, leading to
      tumor progression. This paper shows several cellular and molecular events
      involved in the regulation of the immune response against tumor cells. The
      interaction of several molecules such as MHC, TcR, adhesins, tumor antigens and
      cytokines are discussed, as well as the most recent knowledge about escape
      mechanisms and immunotherapy.

PMID- 7502158
TI  - [Considerations on human rabies transmitted by bats].
AB  - The purpose of this study is to present a combined analysis of eight outbreaks of
      human rabies transmitted by bats in Brazil and Peru. Some factors present in many
      outbreaks were identified, as follows: most of the outbreaks occurred in small
      villages in the rural Amazonian region; there was a change of local production
      processes; little or no cattle was present; the houses were vulnerable; access to
      health services was difficult. Other information was also analyzed, for instance:
      attack rate; incubation period; site of the attack; occupation, sex and age of
      the victim. As part of the study of these recent outbreaks, a review of the
      bibliography on human rabies transmitted by bats was also carried out.

PMID- 7502159
TI  - [Cost effectiveness and health sector reform].
AB  - The cost-effectiveness of a health intervention is an estimate of the relation
      between what it costs to be provided, and the improvement in health which results
      from such intervention. Health may improve because the incidence of illness or
      injury is reduced, because death is avoided or delayed, or because the duration
      or severity of disability is limited. The calculation of this health benefit
      combines objective factors, such as the age at incidence and whether or not the
      outcome is death, with subjective factors such as the severity of disability, the
      judgement as to the value of life lived at different ages, and the rate at which
      the future is discounted. The construction and interpretation of the estimate are
      explained. Also, the paper examines whether the concept of cost-effectiveness is
      consistent with ethical norms such as equity, and concludes that they are not in
      conflict. Finally, it addresses the question of how to incorporate cost
      effectiveness into a health sector reform, and possible ways to implement it.

PMID- 7502160
TI  - [1st workshop on linking epidemiological research to cancer prevention and
      control programs].

PMID- 7502161
TI  - [Determining the degree of stenosis of the internal carotid artery in the
      surgical specimen after eversion TEA--comparison with cw-Doppler ultrasound and
      DSA].

PMID- 7502162
TI  - [Lymphangioleiomyomatosis].

PMID- 7502163
TI  - [Pulmonary complications in HIV-positive patients with advanced immune deficiency
      (less than 200 helper cells)].

PMID- 7502166
TI  - [Radiation exposure of the patient exemplified by lateral cranial image in
      digital luminescence radiography in comparison with the film-screen system].

PMID- 7502165
TI  - [Practical applications of turbo spin-echo sequences in routine MR diagnosis of
      the cerebrum].

PMID- 7502164
TI  - [Diagnosis of extensive stenosing esophageal lipoma].

PMID- 7502167
TI  - Splenic injury.

PMID- 7502168
TI  - Complete transection of the common bile duct following blunt abdominal trauma. A
      case report.

PMID- 7502169
TI  - Splenic injuries--preservation or sacrifice? A clinical update.

PMID- 7502170
TI  - Can pulse oximetry detect raised intracompartmental pressure?
AB  - Pulse oximetry has been advocated as a simple noninvasive investigation of
      vascular compromise. Its usefulness in aiding diagnosis of microvascular
      compromise in a developing compartment syndrome is questioned. This study
      investigates the reproducibility of pulse oximetry and the effect on arterial
      haemoglobin saturation of raising limb intracompartmental pressure by compression
      bandaging. In 32 out of 50 normal subjects there was a difference in percentage
      saturation between right and left arms, with a 2% difference in 6 people (12%).
      Percentage saturation fell significantly at average bandage pressures of 80 mmHg
      (P < 0.0001) and 60 mmHg (P < 0.001). At clinically relevant pressures, the test
      had a sensitivity of 40.4%. With a greater than 50% risk of a false-negative
      result, pulse oximetry is not an appropriate additional investigation in the
      detection of raised intracompartmental pressure.

PMID- 7502171
TI  - Diagnosis and management of paediatric brainstem gliomas.
AB  - A review of paediatric brainstem gliomas (BSGs) treated in the Department of
      Radiation Oncology of the University of the Witwatersrand teaching hospital group
      is presented. Eleven patients between the ages of 4 years and 9 years were seen
      in the period 1982-1992. Of these cases, 9 were diffuse, 1 focal and 1 exophytic;
      the radiological features classifying these primary brainstem tumours are
      described. The survival from initiation of treatment was longest for the
      exophytic type BSG (72 weeks), while little difference in survival between the 9
      diffuse type BSGs (mean 21.5 weeks) and the single focal type BSG (21 weeks) was
      found. The treatment is described and the role of hyperfractionated radiotherapy
      is reviewed.

PMID- 7502172
TI  - 'Spontaneous ileorectostomy' complicating a leaking Hartmann's pouch. A case
      report.
AB  - Leakage from the closed rectal stump following Hartmann's procedure appears to be
      more common than previously suspected. A case of a leaking Hartmann's pouch
      further complicated by an ileorectal communication is reported. Non-operative
      attempts to seal this 'spontaneous ileorectostomy' failed.

PMID- 7502173
TI  - Intraduct carcinoma of the breast (duct carcinoma in situ).
AB  - A retrospective study of non-invasive ductal carcinoma in situ in a series of
      women is presented. The epidemiology, clinical characteristics and results in 65
      patients treated by mastectomy or breast-conserving surgery, with or without
      radiation therapy, are reported. The significant recurrence rate and high
      proportion of invasive cancers among patients with recurrences are noted.
      Recurrences were more frequent in patients with larger tumours and those with
      comedo-type intraduct carcinomas. Implications and guidelines for therapy are
      presented.

PMID- 7502175
TI  - Functional endoscopic sinus surgery--the South African experience.
AB  - Questionnaires were sent to 148 South African otorhinolaryngologists to ascertain
      their experience of functional endoscopic sinus surgery (FESS). The Messerklinger
      approach to FESS was followed by 87% of the surgeons who responded. In South
      Africa FESS is performed mainly under general anaesthesia. An incidence of 1.3%
      is reported in respect of major complications. Information obtained from the
      questionnaires describes training and supports further study. Registrars need
      more than knowledge and surgical experience; their skills must also be assessed
      by some form of certification.

PMID- 7502174
TI  - A new oesophageal dilator.
AB  - A new and safe oesophageal dilator, which eliminates most of the risks of known
      dilators, is described. The technique for its use is also described. A brief
      comparison with other dilators is made, and the satisfactory results of the new
      dilator are indicated.

PMID- 7502176
TI  - Adverse events in a surgical intensive care unit--a cause of increased mortality.
AB  - The incidence and nature of and the outcome following adverse events were studied
      prospectively in a surgical intensive care unit over a period of 1 year. From a
      total of 657 patients, 229 (34.8%) suffered 369 adverse events. The number of
      adverse events per patient ranged from 1 (58.1%) to a maximum of 4 (6.1%). The
      overall mortality rate was 23.4%. Eighty-seven deaths (20.3%) occurred in
      patients not suffering an adverse event and 67 (29.3%) in those whose treatment
      was complicated by an adverse event (P < 0.02). There was no significant
      difference in mortality between patients with single or multiple events. Twenty
      two patients died as a direct result of the event, the commonest reason being
      loss of airway control. Adverse events contribute significantly to mortality in
      critically ill patients.

PMID- 7502177
TI  - Paediatric acute renal failure. A report on 2 cases successfully managed with
      continuous venovenous haemodiafiltration.
AB  - In critically ill patients continuous venovenous haemodiafiltration (CVVHD) is a
      method of renal replacement therapy gaining popularity. The advantage of CVVHD
      over intermittent haemodialysis and peritoneal dialysis lies in the accurate
      control of ultrafiltration and of solute clearance. Two paediatric patients with
      acute renal failure treated successfully with CVVHD are described. The role of
      CVVHD in renal supportive therapy in South African paediatric intensive care
      units is discussed.

PMID- 7502178
TI  - Continuous venovenous haemodiafiltration--an audit demonstrating control of
      electrolytes with haemodynamic stability in the critically ill.
AB  - OBJECTIVE: Renal replacement therapy has evolved significantly in the last 15
      years, resulting in a large diversity of techniques with differing attributes.
      Theoretical advantages of the continuous over intermittent techniques in
      critically ill patients include haemodynamic stability and a reduction in
      disequilibrium syndrome. Limited clinical evidence supports this, but a clear
      reduction in mortality or morbidity has yet to be shown. The technique of renal
      replacement therapy in the Intensive Care Unit at Baragwanath Hospital was
      recently revised and a retrospective study of the haemodynamic and electrolyte
      changes associated with implementing continuous venovenous haemodiafiltration
      (CVVHD) was carried out. METHOD: A retrospective analysis of demographic data,
      haemodynamic and physiological parameters in 10 consecutive patients receiving
      CVVHD during a 10-week period was conducted. Patients' systolic (SBP), and mean
      (MAP) arterial blood pressures, heart rates (HR), and central venous pressures
      (CVP) during the first 36 hours after the implementation of CVVHD were reviewed.
      Serum creatinine, urea and potassium values were also collated. Other organ
      system failures and outcomes were noted. RESULTS: HR decreased by 6.1% (SD 1.5)
      and average MAP rose (12.1%; SD 7.8) as did SBP (12.4%; SD 6.3), compared with
      the values immediately before CVVHD: CVP was unchanged. Control of hyperkalaemia
      was effected in all cases. Serum urea and creatinine levels were well controlled,
      and clearances were closely related to the dialysate flow. Although the mortality
      rate was high, it was lower than predicted. No deaths were directly attributable
      to acute renal failure or complications of CVVHD: CONCLUSION: In the critically
      ill, CVVHD provides excellent serum urea and creatinine clearance and control of
      electrolytes without further compromise of haemodynamics. The low associated
      morbidity, the ease of implementation and the efficacy of the technique may make
      CVVHD the technique of choice for ARF in the intensive care unit.

PMID- 7502179
TI  - The effect of treatment regimens for vaginitis and cervicitis on vaginal
      colonization by lactobacilli.
AB  - BACKGROUND AND OBJECTIVES: The goal of this study was to determine the effect of
      various treatment regimens on vaginal colonization by H2O2-positive and H2O2
      negative lactobacilli. STUDY DESIGN: The subset of women enrolled in a large
      longitudinal cohort study who had Chlamydia trachomatis (n = 13), bacterial
      vaginosis (n = 105), yeast vaginitis (n = 15), or mucopurulent cervicitis (n =
      47) were compared with 93 women without genital infection from the same
      population. The effect of various treatment regimens on lactobacilli was
      evaluated. RESULTS: Use of doxycycline, azithromycin, clotrimazole, and
      fluconazole had little effect on vaginal colonization by Lactobacillus. Use of
      oral or vaginal metronidazole led to an increase in Lactobacillus, which
      persisted 1 month after therapy. Intravaginal clindamycin use caused a decrease 1
      week post-therapy, but at 1 month, levels of lactobacilli were similar to those
      in the metronidazole treatment group. Women treated with oral ampicillin had a
      modest increase in Lactobacillus levels. CONCLUSIONS: Use of antimicrobial agents
      for treating vaginitis and cervicitis do not cause a decrease in vaginal
      colonization by Lactobacillus, which is detectable 1 week to 1 month after
      treatment.

PMID- 7502180
TI  - The cost effectiveness of azithromycin for Chlamydia trachomatis infections in
      women.
AB  - BACKGROUND AND OBJECTIVES: Azithromycin, an approved single-dose therapy for
      cervical chlamydia infections, costs four times as much as doxycycline, the
      standard multidose theapy. GOAL OF THIS STUDY: This study examined whether
      azithromycin is cost effective for treating cervical chlamydia infections. STUDY
      DESIGN: Two diagnostic strategies were compared: 1) laboratory confirmation of
      chlamydia, and 2) presumptive diagnosis from the perspective of the healthcare
      system and the publicly funded clinic. RESULTS: From the healthcare perspective,
      the cost per case of pelvic inflammatory disease prevented with azithromycin
      ranges from a savings of $3,502 for laboratory confirmation to a cost of $792 for
      presumptive diagnosis. From the publicly funded clinic perspective, the cost per
      case of pelvic inflammatory disease prevented ranges from $709 for lab-confirmed
      diagnosis to $3,969 for presumptive treatment. CONCLUSION: For the healthcare
      system, azithromycin is a cost-effective alternative to doxycycline. However, the
      cost of azithromycin must decrease markedly for it to be less costly to the
      publicly funded clinic.

PMID- 7502181
TI  - The epidemiology of human immunodeficiency virus and other sexually transmitted
      diseases in the Stockholm area.
AB  - BACKGROUND AND OBJECTIVES: In Sweden, human immunodeficiency virus has been
      almost exclusively spread in three subpopulations. These are homosexual men
      (47%), intravenous drug abusers (21%), and immigrants from highly endemic areas
      (22%). In contrast to human immunodeficiency virus, gonorrhea and syphilis have
      in the past affected the general population in Sweden. Today, gonorrhea and
      syphilis, like human immunodeficiency virus, are referred to the subpopulations.
      The only sexually transmitted disease that affects the general population is
      chlamydia. GOAL OF THIS STUDY: This is a descriptive analysis of the epidemiology
      of human immunodeficiency virus and the other STDs in the Stockholm area, and an
      inquiry regarding whether these diseases have been spread in the general
      population. The goal also was to evaluate the actual risk of exposure to human
      immunodeficiency virus and the other sexually transmitted diseases in the general
      population and in the subpopulations. STUDY DESIGN: The homosexual subpopulation
      in the Stockholm area has been estimated at 14,000, or 2.5% of the males. More
      than 95% of the human immunodeficiency virus-infected homosexual males have been
      found in the 15 to 64-year-old age group. There are 3,000 to 4,000 drug abusers
      in the Stockholm area, with about 3,000 known to social workers. The third
      subpopulation with a high prevalence of human immunodeficiency virus-infected
      individuals is immigrants from sub-Saharan Africa. It is estimated that in the
      Stockholm area about 9,000 of the individuals in this sub-population are in the
      sexually active age-group, 15-64 years old. RESULTS: Through January 1995, 3,958
      cases of human immunodeficiency virus have been reported in Sweden, of which 65%
      (2,543) were reported in the Stockholm area. Human immunodeficiency virus in the
      Stockholm area in 1994 was calculated as occurring among 6% of the homosexual
      men, 13% of the intravenous drug abusers, and 4% of the immigrants from sub
      Saharan Africa. The relative increases (observed number of new cases in a
      particular year/number of known cases) were 10%, 4%, and 43%, respectively.
      CONCLUSION: The Swedish strategy against sexually transmitted diseases, including
      human immunodeficiency virus, has been successful regarding the spread in the
      general population. The human immunodeficiency virus epidemic has remained
      confined to distinct risk groups. Gonorrhea and syphilis are being eradicated and
      the chlamydia trend is declining.

PMID- 7502182
TI  - Risk factors for infection in women undergoing testing for Chlamydia trachomatis
      and Neisseria gonorrhoeae in Manitoba, Canada.
AB  - BACKGROUND AND OBJECTIVES: Despite sharing common modes of transmission,
      characteristics of individuals infected with Chlamydia trachomatis differ in
      several respects from those with Neisseria gonorrhoeae infection. Further
      characterization of women at high risk for chlamydial infection is needed to
      deliver appropriate and effective preventive, diagnostic, and therapeutic care to
      this population. GOAL OF THIS STUDY: The demographic and socioeconomic
      characteristics of women with laboratory confirmed chlamydia, gonorrhea, or
      coinfection were compared with those of control women who tested negative for
      both pathogens. STUDY DESIGN: A random sample of 400 women in Manitoba, Canada,
      who had undergone testing for sexually transmitted diseases at a public health
      laboratory in 1988 were studied. After linkage with medical insurance and census
      databases, logistic regression analysis was used to compare age, ethnicity, urban
      status, and mean income (using postal codes) of women with gonorrhea alone,
      chlamydia alone, and coinfection, with the same data for women who tested
      negative for both organisms. RESULTS: Young age, North American Indian status,
      urban residence, and low mean income according to postal code were significantly
      associated with gonococcal and chlamydial infection in the study population,
      compared with women who tested negative for both infections. Young age, Indian
      status, and urban residence also were associated with gonorrhea infection alone.
      Only young age and Indian status were associated with chlamydial infection. Mean
      incomes of women with chlamydial infection alone and control subjects were higher
      than those of women with gonorrhea and gonorrhea and chlamydia coinfection.
      CONCLUSIONS: Differences in the demographic and socioeconomic characteristics of
      women with gonorrhea, chlamydia, and coinfection suggest the existence of
      multiple reservoirs of infection due to these agents in the study population. The
      preventive, diagnostic, and therapeutic strategies of sexually transmitted
      disease control programs must be adapted to the individual needs of identified
      high-risk groups.

PMID- 7502183
TI  - Bacterial vaginosis is not important in the etiology of cervical neoplasia: a
      survey on women with dyskaryotic smears.
AB  - BACKGROUND AND OBJECTIVES: It has been suggested that bacterial vaginosis may
      play a role in the etiology of cervical neoplasia. The authors analyzed the
      prevalence, risk factors, and impact on histologic changes of bacterial vaginosis
      in women with cytological abnormalities of the uterine cervix. METHODS: Two
      hundred-eighty women with dyskaryotic smears were surveyed. Using a
      questionnaire, data were obtained on smoking habits and sexual history. Bacterial
      vaginosis was the diagnosis if the vaginal discharge produced a fishy odor upon
      alkalinization and if clue cells were seen in the wet smear. Cervical scrapes
      were analyzed for the presence of human papillomavirus DNA, and cervical tissue
      specimens were analyzed for the presence and severity of (intraepithelial)
      neoplasia and the proliferation rate (mitotic index) of the lesion. Chlamydia
      trachomatis was identified by culture of an endocervical swab. RESULTS: Bacterial
      vaginosis was found in 56 (20%) out of the 280 women. The presence of bacterial
      vaginosis was significantly associated with the number of cigarettes smoked per
      day, age at first sexual intercourse, the lifetime number of sexual partners, and
      current Chlamydia trachomatis infection. The number of cigarettes currently
      smoked per day and the lifetime number of sexual partners were independent
      significant risk factors for the presence of bacterial vaginosis. There was no
      relation between the presence of bacterial vaginosis and the human papillomavirus
      infection. Bacterial vaginosis did not influence the severity of the
      (intraepithelial) neoplasia or the mitotic index. CONCLUSION: In women with
      dyskaryotic cervical smears, the prevalence of bacterial vaginosis did not seem
      to be increased, and bacterial vaginosis did not influence the histologic
      changes. Therefore, bacterial vaginosis is unlikely to be important in the
      etiology of cervical neoplasia, despite the similarity between its epidemiologic
      features and those of cervical human papillomavirus infection and cervical
      neoplasia.

PMID- 7502184
TI  - Condom use among patients attending six sexually transmitted disease clinics in
      Switzerland.
AB  - BACKGROUND AND OBJECTIVES: Persons treated for a sexually transmitted disease
      have been shown to be at increased risk for human immunodeficiency virus
      infection. Levels of condom use among these patients are presented, and
      sociodemographic and behavioral factors associated with self-reported never use
      of condoms are analyzed. STUDY DESIGN: This was a cross-sectional study of 2,257
      patients treated at six sexually transmitted disease clinics in Switzerland
      between July 1990 and December 1992. RESULTS: Overall, 46.3% of the patients
      reported that they had never used condoms. Among heterosexual men, this level was
      48.3% (n = 1,751), among homosexual and bisexual men it was 21.6% (n = 268), and
      among heterosexual women it was 60.1% (n = 238). In a logistic multivariate
      regression analysis, factors significantly associated with never use of condoms
      among heterosexual men included age over 29 years, not of Swiss origin, low level
      of education, few partners in the previous 6 months, contraction of the sexually
      transmitted disease from a stable partner, and not being an injecting drug user.
      CONCLUSION: These results document the high levels of condoms never being used in
      this population and highlight the importance of condom promotion activities
      provided by sexually transmitted disease clinics.

PMID- 7502185
TI  - High-level quinolone resistance in Neisseria gonorrhoeae: a report of two cases.
AB  - BACKGROUND AND OBJECTIVES: Fluoroquinolones are widely used oral agents for
      treating Neisseria gonorrhoeae. Resistance to these agents is sporadic and
      usually at a low level. Two instances of high-dose ciprofloxacin regimens failing
      in the treatment of gonococcal infection, caused by strains with high-level
      quinolone resistance, are reported. STUDY DESIGN: This is a case report.
      CONCLUSION: High-level resistance to quinolone antibiotics resulting in treatment
      failure was observed in two distinct gonococcal isolates from patients infected
      in the Philippines (ciprofloxacin; minimal inhibitory contribution = 16 mg/l).
      Continued monitoring of the quinolone sensitivity of Neisseria gonorrhoeae is
      appropriate and prudent.

PMID- 7502186
TI  - Demographic and behavioral differences among participants, nonparticipants, and
      dropouts in a cohort study of men who have sex with men.
AB  - BACKGROUND AND OBJECTIVES: Results of prospective cohort studies can be biased
      when subjects selectively refuse to participate or be included in follow-up. GOAL
      OF THIS STUDY: To assess the potential for bias in a longitudinal study of sexual
      risk behavior among men who have sex with men. STUDY DESIGN: This was a cross
      sectional comparison of clinical data regarding men who have sex with men
      attending an urban human immunodeficiency virus testing clinic. RESULTS: Of 3,390
      men who have sex with men invited to participate, 2,063 refused, 589 dropped out
      after completing an initial study questionnaire, and 738 participated in follow
      up at 6 months. There were no significant differences in the same-gender sexual
      behaviors of participants, dropouts, and nonparticipants, with one exception:
      Nonparticipants were more likely to abstain from receptive oral sex (27%)
      compared with participants (18%) or dropouts (21%). CONCLUSION: The similarities
      in reported activities among participants, dropouts, and nonparticipants suggest
      that selection bias may have limited impact on cohort studies of sexual behavior.

PMID- 7502188
TI  - Laboratory to laboratory variation in Chlamydia trachomatis culture practices.
AB  - GOAL OF THIS STUDY: To compare laboratory to laboratory variability in methods of
      cell culture for Chlamydia trachomatis performed by North American research
      laboratories. STUDY DESIGN: The authors administered a standardized 54-question
      survey to laboratories that had published articles in any of three medical
      journals reporting on the use of cell culture to identify individuals with C.
      trachomatis infection. Laboratory to laboratory variability in specimen
      collection, specimen transport conditions, culture methodologies, and criteria
      for evaluation of culture outcomes was examined. RESULTS: Twenty-five (93%) of 27
      laboratories responded to the survey. Only two of 54 questions were answered
      uniformly by all responding laboratories. All laboratories reported vortexing or
      sonication of specimens before culture inoculation and centrifugation of
      inoculated cultures prior to incubation. In contrast, substantial variation was
      noted in specimen collection devices, specimen transport conditions and times,
      culture format, culture procedures, and criteria for identifying positive
      cultures. CONCLUSION: Although this study did not evaluate the sensitivity of
      chlamydia cell cultures performed in different laboratories, there was
      substantial laboratory to laboratory variation in nearly every facet of culture
      evaluated. Laboratory to laboratory variation in chlamydia cell culture
      sensitivity likely accounts for part of the substantial variability in published
      evaluations of the sensitivity of nonculture chlamydia diagnostic tests.

PMID- 7502187
TI  - Chlamydial serology among patients with tubal factor infertility and ectopic
      pregnancy in Alexandria, Egypt.
AB  - BACKGROUND AND OBJECTIVES: Little is known about the role of Chlamydia
      trachomatis in the etiology of tubal factor infertility and ectopic pregnancy in
      Egypt. GOAL OF THIS STUDY: To assess the association between past chlamydial
      infection, tubal factor infertility, and ectopic pregnancy in an Egyptian
      population. STUDY DESIGN: This report consists of two concurrent case-control
      studies. First, 51 patients with tubal factor infertility were compared with 48
      healthy subjects who did not have tubal factor infertility and 53 pregnant
      subject subjects. Second, 66 patients with ectopic pregnancy were compared with
      51 pregnant control subjects. RESULTS: Geometric mean titers for Chlamydia
      trachomatis were higher among patients with tubal factor infertility and ectopic
      pregnancy, and they were more likely to have high antichlamydial titers (> or =
      1:128 immunoglobulin G). Serum titer was significantly correlated with histologic
      evidence of salpingitis among the patients with an ectopic pregnancy. CONCLUSION:
      Our findings, similar to those from Western societies, suggest that among
      Egyptian women, prior chlamydial infection is associated with an increased risk
      of tubal factor infertility and possibly ectopic pregnancy.

PMID- 7502189
TI  - The arcade of Frohse: an anatomic study.
AB  - An anatomic study of the appearance and consistency of the upper arcade of the
      superficial layer of the supinator m. was carried out on 106 elbow-joint
      dissections. A classification of the structure was drawn up in order to discern
      the criteria for normality. An arcade of a tendinous nature ("arcade of Frohse")
      was encountered in the majority of cases (64.1%). At first sight, it could not be
      ascribed a compressive role affecting the posterior branch of the radial n.
      Macroscopic examination of the nerve prior to its entry under the supinator
      arcade revealed the presence of macroscopic lesions in 42.9% of cases. This high
      incidence does not permit any conclusions regarding the pathologic significance
      of this type of lesion.

PMID- 7502191
TI  - Anatomo-radiological study of the popliteal artery during knee flexion.
AB  - We studied the morphological modifications of the popliteal artery during knee
      flexion. An anatomical, radiological study consisted of analysis of lateral
      arteriographs in different degrees in joint flexion followed by dissection to
      reveal the anatomical structures involved in the morphological adaptation of the
      popliteal artery to joint movement. In five non-atheromatous volunteers, 15 MRI
      angiographic sequences were done at the level of the knee in extension and
      flexion. The arteriographs and angio MRI showed that as joint flexion increased
      tortuosities appeared in the supra-articular upper popliteal artery while the
      middle and lower parts of the popliteal artery kept an even curve retracted from
      the posterior surface of the joint. Dissection seemed to show that this arterial
      adaptation occurred between two fixed points, one proximal (the adductor canal)
      and the other distal (the origin of the anterior tibial artery). Angio MRI seems
      to be a future route for the assessment of the limb vessels. The contrasting
      behaviour of the different segments of the popliteal artery allows us to
      understand better the pathophysiology of trauma and malpositions of the popliteal
      arterial trunk.

PMID- 7502190
TI  - Biomechanics of the hip: forces exerted during walking.
AB  - Since the work of Pauwels, the forces exerted on the coxofemoral joint during
      walking have been studied either in different spatial planes (frontal, sagittal
      and horizontal) or by three-dimensional spatial analysis. Starting from the
      findings of our own studies, our aim was to compare the two methods of analysis
      (two-dimensional and three-dimensional) in order to provide a better
      understanding of the benefits and limitations of each method. In pursuit of this
      aim, we studied the pressure forces exerted on the coxofemoral joint, using a
      geometric plane technique following a method similar to that of Pauwels [20], and
      with a three-dimensional modelling technique using the finite element method. The
      material, taken from the published literature, was the same in both our studies.
      The results are expressed in terms of the size and orientation of the pressure
      force exerted on the coxofemoral joint during the monopodal weightbearing phase
      of walking. A comparison of these two methods of analysis clearly demonstrates
      the simplicity of two-dimensional analysis (which must incorporate as a minimum
      the frontal plane and the sagittal plane) and the richness of the three
      dimensional analysis. The latter method, by appropriate manipulation of the
      information obtained, provides a starting point for computer simulations
      performed with the aim of testing a biomechanical or therapeutic hypothesis.

PMID- 7502192
TI  - Anatomy of the Achilles tendon (tendo calcaneus) with respect to tendon thickness
      measurements.
AB  - 267 normal controls of different ages underwent achilles tendon thickness
      measurements by ultrasonography (US) for reference. 96 recruits and 10 young
      women additionally underwent magnetic resonance imaging of the achilles tendons
      and calves for more systematic evaluation of the factors influencing tendon
      thickness. Children under 10 had a tendon thickness (mean +/- SD) of 4.6 +/- 0.8
      mm, 10-17 year-olds 6.1 +/- 0.8 mm, 18-30 year-olds 6.3 +/- 0.5 mm and over 30
      year-olds 6.9 +/- 1.0 mm. Women had slightly thinner tendons than men, but the
      difference was statistically significant only in the oldest age group. Normal
      variation in shape of the tendon caused up to a 25% variation in the measured
      thickness values. In the large sample of recruits a statistically significant
      correlation was found between the tendon thickness and body height. Differences
      in population height could account for the measured differences in normal
      achilles tendon thickness found in studies on Japanese subjects compared with
      studies on European and American subjects.

PMID- 7502193
TI  - Arterial vasculature of the stomach and oncologic gastrectomies.
AB  - Preoperative knowledge of the gastric arterial blood-supply with special regard
      to anatomic anomalies is desirable for a correct surgical approach to this viscus
      and for the reduction of intra- and postoperative complication rates. The authors
      report their experience with the use of preoperative digital angiography in the
      evaluation of 46 consecutive patients undergoing gastric cancer surgery. Twenty
      of these (43.5%) presented a vascular anatomy different from the normal pattern.
      In 6 (13%), a double arterial anomaly was detected. Some anatomic anomalies of
      the celiac axis and superior mesenteric artery are described in relation to
      operative procedures during oncologic gastrectomies.

PMID- 7502195
TI  - What will it take?

PMID- 7502194
TI  - Plastination for gross anatomy teaching using low cost equipment.
AB  - Plastination offers a means of keeping anatomical specimens without the usual
      problems associated with wet specimens ie desiccation, mould and specific storage
      requirements. Plastinated specimens are clean and odourless, require minimal
      aftercare and can be stored on shelves or in display cases. These specimens are
      more durable and robust than wet specimens showing similar features. The
      techniques described in this paper for plastination are cost effective, and
      produce good quality, robust specimens using low cost equipment which is readily
      available in most Anatomy departments. The procedures described are easy to
      follow used in conjunction with von Hagens [4] plastination technical notes.

PMID- 7502196
TI  - What is your general approach to the management of brain stem AVMs?

PMID- 7502197
TI  - Delayed recanalization of a cerebral arteriovenous malformation following
      angiographic obliteration with polyvinyl alcohol embolization.
AB  - BACKGROUND: The efficacy of embolization of cerebral arteriovenous malformations
      (AVMs) is presently being evaluated. Embolization of single pedicle AVMs may
      produce complete angiographic obliteration and has been suggested as the sole
      therapy for treating these lesions. METHODS: A 17-year-old female presented with
      a left intraventricular and intraparenchymal cerebral hemorrhage resulting from a
      1 cm left posterior choroidal AVM. She subsequently underwent polyvinyl alcohol
      (PVA) embolization of the AVM with complete angiographic obliteration. RESULTS:
      At 9 months follow-up, no evidence of recanalization of the AVM nidus was seen.
      Two years later, recanalization of the nidus was seen; and the patient received
      radiosurgical treatment. The natural history of previously embolized AVMs is
      reviewed and the mechanisms for recanalization are discussed. CONCLUSION: We
      recommend that patients with angiographic obliteration of AVMs receive further
      treatment, preferably resection, or be followed with serial angiography.

PMID- 7502198
TI  - How to treat incidental cerebral aneurysms: a review of 139 consecutive cases.
AB  - BACKGROUND: Together with current advances in neuroimaging techniques, the chance
      of incidental discovery of unruptured cerebral aneurysms has increased and the
      selection of their appropriate management remains controversial. To provide
      current data about management results of patients with incidental cerebral
      aneurysms, we have made a retrospective review of 139 consecutive patients
      treated either by surgical or conservative means. METHODS: The surgical
      indication for each patient was decided, carefully considering several factors
      respectively, including the surgical difficulty, aneurysm size, patient's age,
      and medical condition. RESULTS: Forty-nine patients were managed conservatively.
      Eight (16%) of those conservatively managed patients had intracranial hemorrhage
      due to aneurysm rupture during the follow-up period (mean, 4.3 years). Seven of
      these eight patients died from a fatal subarachnoid hemorrhage (SAH). The follow
      up data showed that the mean size of aneurysms with late hemorrhage was
      significantly larger than that of aneurysms without subsequent rupture. It was
      also confirmed that none of the 26 tiny aneurysms smaller than 4 mm in diameter
      had ruptured. Ninety patients harboring 119 incidental aneurysms less than 25 mm
      in diameter underwent surgery. There was no surgical mortality or morbidity in
      this series. CONCLUSIONS: These excellent surgical results were presumably
      achieved due to the strict patient selection. In respect to the size of
      aneurysms, it seems to be justified to recommend surgery for patients with
      aneurysms larger than 5 mm in diameter.

PMID- 7502199
TI  - A3-A3 side-to-side anastomosis in the anterior communicating artery aneurysm
      surgery: report of four cases.
AB  - BACKGROUND: Giant or large aneurysms prevent direct clipping without compromise
      of the parent vessels, and any countermeasures should be attempted. METHODS: We
      describe an A3-A3 side-to-side anastomosis as a method of revascularization of
      the pericallosal artery in surgery of an aneurysm of the anterior communicating
      artery (ACoA) in four patients. RESULTS: In two patients with the pericallosal
      artery narrowed or occluded by the clipping or trapping procedure, and in two
      other patients with giant aneurysms clipped with prolonged duration of temporary
      occlusion of the parent vessels, no serious neurologic changes were observed
      after surgery. CONCLUSIONS: We believe that an A3-A3 side-to-side anastomosis is
      effective in preventing ischemic complications in the territory of the
      pericallosal artery.

PMID- 7502200
TI  - Giant aneurysm at the origin of the accessory middle cerebral artery.
AB  - BACKGROUND: Aneurysms of the A1 portion of the anterior cerebral artery are rare.
      The accessory middle cerebral artery is also a rare anomalous artery. CASE
      REPORT: We operated on a 53-year-old man because of a giant aneurysm which arose
      at the junction of the accessory middle cerebral artery and the horizontal
      portion of the anterior cerebral artery (A1 portion). CONCLUSION: This is the
      first report of a giant aneurysm of that region. A detailed evaluation of the
      angiogram is necessary prior to the operation, in order to select the most
      appropriate operative method to secure the blood flow of the accessory middle
      cerebral artery and distal anterior cerebral artery.

PMID- 7502201
TI  - A technique for prevention of donor site pain associated with harvesting iliac
      bone grafts.
AB  - Patients who have undergone anterior cervical spine fusion with an iliac bone
      graft frequently experience donor site pain after surgery. We found that an
      effective technique to avoid donor site pain is to round off the corners of the
      iliac crest with an air drill after harvesting the graft.

PMID- 7502202
TI  - Spontaneous spinal subarachnoid hematoma--case report.
AB  - BACKGROUND: Spinal subarachnoid hemorrhage is unusual, and rarely results in
      spinal subarachnoid hematoma because the cerebrospinal fluid tends to dilute the
      blood and prevent the formation of clots. We describe a patient with spinal
      subarachnoid hematoma of unusual spontaneous origin. CASE: A 66-year-old female
      presented with sudden onset of intense back pain with paraplegia. Magnetic
      resonance imaging demonstrated a mass lesion between T2 and T6, compressing the
      spinal cord anteriorly. Emergency osteoplastic laminotomy exposed a hematoma in
      the subarachnoid space from T2 to T6, but no source of the hemorrhage was found.
      The patient was able to walk by herself about 20 days after the operation.
      CONCLUSION: The outcome is significantly influenced by the duration between onset
      and operation, preoperative neurologic status, and rapidity of symptom
      progression. Therefore, we emphasize the importance of early diagnosis, and rapid
      and complete operative removal of spinal subarachnoid hematoma in order to
      achieve the best outcome.

PMID- 7502203
TI  - Analysis of brain tumors using 1H magnetic resonance spectroscopy.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is superior in delineating anatomic
      and pathologic information and has subsequently been married to the ability of
      magnetic resonance spectroscopy (MRS) to provide insight into the biochemical
      changes underlying pathology. Proton magnetic resonance spectroscopy (1H MRS)
      allows the non-invasive in vivo collection and measurement of chemical
      information from a selected volume of tissue (voxel). METHODS: We conducted a
      prospective trial in 23 patients with brain mass lesions and 16 normal subjects
      using proton magnetic resonance spectroscopy (1H MRS). The spectra were analyzed
      for N-acetyl-aspartate (NAA), choline compounds (Cho), creatine (Cr), and lactate
      (Lac). The ratios of the compounds in tumors were compared to normals. RESULTS:
      The tumors showed significant decreases in the mean peak height ratios of
      NAA/Cho, NAA/Cr, and significant increases in Cho/Cr when compared to tissue from
      normal subjects. Cho was elevated in all of the meningiomas and gliomas. In
      benign tumors, Cho was usually elevated while in metastases Cho was often normal
      or decreased. The four metastatic tumors showed NAA/Cho, NAA/Cr, and Cho/Cr that
      were similar to controls. Lac varied with tumor type and was elevated in many
      malignant primary brain tumors. CONCLUSIONS: 1H MRS is a powerful tool for safe,
      noninvasive analysis of tissue chemistry in vivo. Analysis of intracranial tumors
      reveals significant trends that might eventually be used in the classification of
      tumor histology and evaluation of the efficacy of tumor treatment.

PMID- 7502204
TI  - A comparison of intraarterial carboplatin and ACNU for the treatment of gliomas.
AB  - BACKGROUND: Intraarterial chemotherapy with carboplatin for malignant gliomas has
      been tried recently, but its therapeutic efficacy and toxicity have not yet been
      elucidated. METHODS: We treated patients with malignant glioma by intraarterial
      chemotherapy using carboplatin, and compared the efficacy as well as the side
      effects with intraarterial ACNU. RESULTS: Twenty patients were treated with
      carboplatin (300 mg/m2) and 22 patients were treated with ACNU (80-200 mg/m2).
      Response (complete remission+partial response) rate for carboplatin was 12.5%
      compared to 45% for ACNU. Despite higher response rate for ACNU, the difference
      in the survival curves of the two groups was not significant. Three patients who
      were treated with high dose (150-200 mg/m2) of ACNU developed hemiparesis and
      aphasia. Seven patients treated with carboplatin developed 10 incidences of
      neurotoxicities; two hemiparesis, one aphasia, one blindness, one visual field
      disturbance, three convulsions, and two developed incidences of disturbances of
      consciousness. CONCLUSIONS: Intraarterial carboplatin was not superior to
      intraarterial ACNU in achieving remissions, and showed much greater tendency to
      produce neurotoxicities.

PMID- 7502206
TI  - Importance of prevention of intravenous thrombosis and preservation of the venous
      collateral flow in bridging vein injury during surgery: an experimental study.
AB  - BACKGROUND: Venous infarction (cerebral edema and/or hemorrhage) may occur
      several hours after sacrifice of the bridging vein during surgery. However, in
      our experience, severe venous infarction is often produced by prolonged brain
      retraction in addition to sacrifice of the vein. METHODS: The experiment was
      carried out using 20 adult cats. In five cats, all bridging veins were coagulated
      near the superior sagittal sinus and 12 hours later the surgical wound was closed
      (group A). In five other cats, a round plate weighing 45 g was placed on the
      center of the Sylvian fissure for 12 hours and then the wound was closed (group
      B). In the remaining 10 cats, both of these interventions were performed (group
      C). All 20 animals were sacrificed 12 hours after the wound closure. RESULTS: The
      degree of Evans-blue dye leakage and brain edema was much more marked in the
      group C than in groups A and B. The endothelial intactness of the bridging veins
      studied by staining with a factor VIII-related antigen was much more disturbed in
      group C than in the other groups. CONCLUSIONS: The endothelium of the cortical
      veins is damaged much more by the combination of sacrifice of the vein and brain
      retraction, and this endothelial damage of the cortical vein leads to extensive
      venous infarction.

PMID- 7502205
TI  - Experimental study of intraoperative local chemotherapy with fibrin glue
      containing nitrosourea for malignant gliomas.
AB  - BACKGROUND: Local control of the tumor bed after removal of a tumor is one of the
      most important points in the treatment of malignant gliomas. This study was
      designed to examine whether fibrin glue is useful as a vehicle for sustained
      release of intraoperative local chemotherapy with nitrosourea (ACNU). METHODS:
      The growth-inhibiting activity of ACNU on C6 glioma cells and ACNU released into
      5-mL supernatant saline from fibrin glue containing 5 mg/mL (10 mg) of ACNU was
      measured in vitro. C6 tumor inoculated in rat brains was covered with fibrin glue
      containing either 2 mg/mL or 5 mg/mL of ACNU for 5 days, and the histologic
      changes were examined. RESULTS: ACNU inhibited the growth of C6 glioma cells in a
      dose-dependent manner, and the drug concentration required for 50% inhibition of
      cell growth (IC50) was about 4 micrograms/mL with 1 hour of treatment. Although
      about 50% of all ACNU included in the fibrin glue was released in the first hour,
      an effective concentration over the value of IC50 was sustained even after 12
      hours. A histologic examination showed tumor cells damaged within a depth of
      about 2-3 mm from the tumor surface covered with fibrin glue containing ACNU.
      CONCLUSIONS: Fibrin glue may be useful as a vehicle for sustained-release
      chemotherapy, and intraoperative local chemotherapy with fibrin glue containing
      anticancer agents such as nitrosourea may be helpful in the local control of
      malignant gliomas.

PMID- 7502207
TI  - Percutaneous transluminal angioplasty in a canine model of cerebral vasospasm:
      angiographic, histologic, and pharmacologic evaluation.
AB  - BACKGROUND: Cerebral vasospasm following subarachnoid hemorrhage (SAH) is one of
      the leading factors that deteriorate the clinical outcome after aneurysmal
      surgery. Percutaneous transluminal angioplasty (PTA) is a method to directly
      dilate the constricted vessel using the intravascular neurosurgical technique.
      METHODS: Angiographic, histologic, and pharmacologic evaluations related to PTA
      are presented, using a canine double-injection model of SAH. In angiographic
      evaluation, we studied the effect of PTA performed on day 1, 4, or 7 of SAH. We
      performed sequential histologic study by light microscopy using the same for the
      angiographic evaluation. In pharmacologic evaluation, we measured in vitro
      isotonic constrictive force using two vasoconstrictors immediately after PTA on
      normal basilar arteries (control group) and basilar arteries on day 7 of SAH.
      RESULTS: In angiographic evaluation, we observed the effective dilation of
      spastic artery immediately after PTA and saw no recurrence of vessel constriction
      when PTA was performed on day 7 of SAH. However, the preventive effect of PTA was
      inconsistent when it was performed earlier after SAH (days 1, 4). In histologic
      evaluation, PTA segments immediately after PTA showed denuding of endothelial
      cells and stretching of the internal elastic lamina without disruption of the
      muscle layer. In pharmacologic evaluation, there was no difference in isotonic
      constrictive force created by vasoconstrictors between the PTA and non-PTA
      segments without SAH. However, there was a statistically significant reduction of
      isotonic constrictive force on the PTA segment with SAH. CONCLUSIONS: We suggest
      that the mechanism of PTA vasodilation in vasospasm after SAH may result from
      mild functional changes in the vascular wall when PTA was applied on day 7 of
      SAH. The functional changes would not be adequately induced to prevent recurrence
      of vasoconstriction when PTA was applied soon after SAH.

PMID- 7502209
TI  - Subgaleal preservation of calvarial flaps.
AB  - An alternative method of preservation of the skull bone flap in the subgaleal
      space is described. The method was used in eight patients and the flap was
      successfully replaced to the original site in four of these cases. The period of
      preservation varied from 3-16 months. The procedure had the advantages of ease of
      placement and prolonged survival of flap.

PMID- 7502208
TI  - Changes in the cerebrocortical capillary network following venous sinus occlusion
      in cats.
AB  - BACKGROUND: Although the important protective effect of venous collateral
      pathways in sinus occlusion on parenchymal injury has been demonstrated in
      previous works, the vascular response in the capillary microcirculation itself
      after cerebral venous occlusion has not been fully elucidated. We examined the
      morphology of the capillary network after venous occlusion by relating
      stereologic morphometric parameters to changes in local cerebral blood flow and
      the development of brain edema. METHODS: Experimental venous sinus occlusion was
      induced by injection of 0.5 mL of cyanoacrylate into the superior sagittal sinus
      and by immediate ligation of both external jugular veins in chloralose-urethane
      anesthetized cats (n = 24). Capillaries in the adjacent cortex (marginal and
      suprasylvian cortex) and remote cortex (piriform cortex) were injected with Evans
      blue dye 2 minutes before sacrifice at 15-minute and 120-minute postsinus
      occlusion. The stereologic morphometric parameters including volume density,
      minimum intercapillary distance, capillary diameter, and number of perfused
      capillaries were computed on a fluorescence microscopic photograph using an image
      analysis system. Cerebral blood flow (CBF) was measured by hydrogen clearance
      method, and brain tissue water content was measured using the dry-wet method.
      RESULTS: In the cortex adjacent to the superior sagittal sinus, the volume
      density and the number of perfused capillaries were increased significantly (p <
      0.02, and p < 0.05, respectively) and the minimum intercapillary distance was
      decreased significantly (p < 0.02) at 15 minutes after venous occlusion (n = 10).
      Cerebral blood flow (CBF) was also decreased to 53% of that in the control group
      (p < 0.01). Although the morphologic parameters returned to the control level by
      120 minutes after venous occlusion, the CBF remained decreased after venous
      occlusion. No change was observed in the water content of the adjacent gray
      matter at 15 minutes after venous occlusion; however, it was increased (p < 0.05)
      at 120 minutes. CONCLUSION: These results indicate that the recruitment of
      reserve capillaries occurs during the early phase of venous occlusion. While CBF
      decreased to half of the control after venous occlusion, capillary perfusion
      remained above or near the control level until 120 minutes postocclusion,
      suggesting that venous recruitment would be potentially beneficial in clinical
      patients in the early stage of venous occlusion.

PMID- 7502210
TI  - Disseminated intravascular coagulation.

PMID- 7502211
TI  - All the news that's fit to print?

PMID- 7502212
TI  - CSF leak after acoustic neuroma surgery.

PMID- 7502213
TI  - [Orthopedic examination of the foot: refresher course].

PMID- 7502214
TI  - [Comparison of types of accidents in field and indoor soccer].

PMID- 7502215
TI  - [Ultrasound follow-up of experimental muscle injuries].
AB  - Experimental muscle lesions were produced in 28 rabbits by stab incision, thus
      creating a lesion of known extent and site. The changes in the course of healing
      were followed up and documented at short intervals for a period of two months via
      sonography. The changes take place in regular course and can be explained by fine
      tissue changes, taking into consideration the fundamentals of theoretical
      ultrasound physics. Sonography renders both valuable assistance in diagnosing
      muscular lesions and in following up the healing process--the latter, however,
      with some reservations due to the clinical terminology defining the extent of
      muscular lesions.

PMID- 7502216
TI  - [Proprioceptive capacities of the healthy knee joint: modification by an elastic
      bandage].
AB  - In 30 healthy volunteers with clinical inconspicuous knee joints, the
      proprioception of the knee joint was evaluated. The proprioceptive capability of
      the subjects was tested by an angle reproduction test. Additionally all knee
      joints were measured with and without an elastic knee bandage. The study showed
      no difference, neither between the left and the right knee joint, nor between men
      and women. However, at the mid-range of knee joint motion a significant
      deterioration of the proprioception could be documented. Applying an elastic knee
      bandage resulted in a significant improvement of the results.

PMID- 7502217
TI  - [Injuries in horseback riding--incidence and causes].
AB  - This article presents the examination of 78 accidents in horseback riding,
      referring to their origin and kind of injury. It was found that 76% of all
      injuries did not occur during the active phase of riding, but in the time just
      before and right after it. Children without any experience in horseback riding
      were most susceptible to injuries. Referring to lesions occurring before and
      after the active phase, the longer extremity was predominantly involved (40%);
      furthermore, the skull was injured in 18% and the hand in 14% of all lesions.
      During the active phase of horseback riding, skull injuries increased to 34%.
      Thoracic and spinal lesions occurred in 15% each. The frequency of all lesions
      shows a reversed proportional dependence on the amount of experience in this
      sport. Severity of the accidents increases significantly with increasing demand
      on performance. In consideration of these studies the thesis can be advanced that
      coordinated prevention directly before and after the active riding phase can
      decrease the frequency of all accidents and especially the involvement of the
      lower extremity and the skull.

PMID- 7502218
TI  - [Etiological accident types and recommendations for prevention in basketball].
AB  - The study is based on 128 basketball accidents. The following accident types were
      discovered: ankle sprains 54.7%, handling the ball (saving and catching) 15.6%,
      knee-joint-distorsions 10.2%, collisions, blows and kicks 11.7%, falls 3.9%,
      spontaneous damage of muscles and tendons 1.6% and getting hurt because of the
      equipment in the gym 2.3%. Prophylactic precautions might be physiological or
      synthetic taping, proprioceptor training and preventive sports medical checkups.

PMID- 7502219
TI  - [Are school sports too dangerous?].

PMID- 7502220
TI  - [Treatment of muscular injuries with diclofenac-diethylammonium emulsion gel].

PMID- 7502221
TI  - [Muscular imbalances in high performance swimmers: damage to the locomotor
      system].

PMID- 7502222
TI  - [Open and closed kinetic chain in rehabilitation after athletic injuries].

PMID- 7502223
TI  - [The secondary prevention of colorectal carcinoma by polyp removal].
AB  - PURPOSE: Colorectal adenomas are established precursor lesions of colorectal
      carcinoma. Molecular biologic investigations suggest a developing cycle from
      normal mucosa and adenoma to carcinoma via influence of oncogens and tumor
      suppressor genes. Polypectomy is supposed to reduce the colorectal cancer risk.
      PATIENTS AND METHODS: Studies published in this field until now were analysed and
      it was discussed whether consequent endoscopic polypectomy of colorectal adenomas
      adds to secondary prevention of colorectal carcinoma. RESULTS: A variety of
      studies has shown that removing the precursors of colorectal carcinoma leads to a
      distinct reduction of colorectal carcinoma. A large American prospective study
      has confirmed these observations and has shown that compared to the expected
      incidence, found in large population studies, the risk of colorectal carcinoma
      can be reduced by up to 90%. As a consequence, besides complete polypectomy the
      regular follow-up is mandatory to detect and treat recurrent polyps. CONCLUSION:
      Consequent endoscopic polypectomy of all colon adenomas which today usually is
      performed with a diathermy loop is a secondary prevention of colorectal
      carcinoma. The surveillance should be performed along the lines of the German
      Cancer Society.

PMID- 7502224
TI  - Radiotherapy and adjuvant chemotherapy for childhood medulloblastoma. The Royal
      Marsden Hospital experience.
AB  - PURPOSE: We reviewed the outcome of children with medulloblastoma treated from
      1970 to 1985 with combined radiotherapy and chemotherapy. PATIENTS AND METHODS:
      Fifty-seven children with a median age of 8 years (range 1 to 16 years) at
      diagnosis were analyzed regarding survival, site and time of recurrence,
      treatment toxicity, prognostic factors and performance status. RESULTS: The
      overall 5- and 10-year-survival was 66% and 54%, respectively. Patients with
      subarachnoid metastases or positive cerebrospinal fluid cytology (M1-3) had a
      shorter survival compared with those without it (p < 0.1). Furthermore, survival
      appeared to improve with the addition of lomustine (CCNU) to vincristine
      chemotherapy with a 5-year-survival of 70% versus 31% (relative risk 3.4, 95%
      confidence interval 1.4 to 8.1) although it should be noted that these were
      consecutive not randomized patients treated. Of the 52 patients achieving
      remission, 17 relapsed either in primary (2), spine (5) or a combination of these
      (10). Two patients developed bone metastases without central nervous system
      recurrence. Performance status measured crudely appeared to be good in long-term
      survivors. Of 31 patients that survived for long-term follow-up and had their
      performance evaluated, 28 had no or minor residual neurological signs and the
      remaining 3 were disabled. CONCLUSION: Combined modality treatment for
      medulloblastoma in childhood was able to cure 54% of patients with a good
      performance status in the majority of survivors.

PMID- 7502225
TI  - [The combined use of photodynamic therapy with ionizing radiation on breast
      carcinoma cells in vitro].
AB  - PURPOSE: The photodynamic therapy is a technique by which the tumor cells are
      selectively sensitized to destruction by light of an appropriate wavelength. The
      aim of this work is to analyze the biological effectiveness of photochemical
      reactions induced by laser light in tumor cells exposed to photosensitizers.
      MATERIAL AND METHODS: The toxicity of the 2 photosensitizers zinc phthalocyanine
      (ZnPC) and meso-tetrahydroxyphenylchlorine (m-THPC) as well as the biological
      effect of the combination of sensitizers with laser light were tested in vitro by
      means of a colony forming assay. In addition, the influence on the photodynamic
      reaction of a previous exposure of the tumor cells to ionizing radiation has been
      tested. RESULTS: For both sensitizers doses of 5 micrograms per milliliter of
      culture medium showed low toxicity, i.e. the survival of the treated cells
      exceeded 90%. For laser treatments the dose permitting 90% survival was
      determined to be around 10 J/cm2. With these doses, the combined application of
      photosensitizers and laser light proved to be very effective and resulted in a
      nearly complete reduction of survival. As expected, irradiation of the cells with
      doses of 1 and 2 Gy of X-rays reduced the survival to 66 and 47%, respectively,
      compared to untreated controls. Cells surviving such treatment showed no changes
      either in the response to treatments with photosensitizers or to combined
      applications of photosensitizers and laser light. CONCLUSION: The effects of
      photodynamic treatment by ionizing radiation seem to be additive and independent
      of each other. So, our preliminary results are quite encouraging and point out
      the need of further detailed studies in view of the intended clinical application
      of this new kind of a local treatment.

PMID- 7502226
TI  - [The postoperative therapy of epithelial ovarian carcinoma. Has systemic
      cytostasis replaced percutaneous radiation?].
AB  - BACKGROUND: Abdominopelvic external beam radiotherapy as a primary postoperative
      therapy after a comprehensive surgical staging in completely resected stages
      ovarian carcinoma has been used worldwide less frequently during the last decade
      despite proven curative effects of this therapeutic modality. Systemic
      chemotherapy, mostly platinum-based combination chemotherapy, has been
      established as a postoperative routine treatment because of the high response
      rates achieved in advanced cases of disease. The controversy concerning the
      choice of chemotherapy continues and gave rise to a review of recently reported
      treatment outcome data. PATIENTS AND METHODS: As a result of the low incidence of
      ovarian carcinoma diagnosed in early stages, only a few randomized clinical
      trials have been performed of both systemic chemotherapy and external beam
      radiotherapy in intermediate/high risk patients. Thus we collected data based on
      a review of the literature with special regard to criteria recommended to select
      patients for postoperative abdominopelvic radiotherapy and chemotherapy
      respectively. RESULTS: Despite high response rates and high negative second-look
      operation findings to chemotherapy, the rates for cures and long-term survival
      have not been improved significantly and have also failed to show a significant
      advantage compared with results achieved by the use of external beam
      radiotherapeutic modalities. CONCLUSIONS: Long-term survival rates of the
      relative small number of ovarian carcinoma patients in the early stages treated
      in prospective randomized trials comparing both treatment modalities do not
      justify the assumed superiority of chemotherapy over radiotherapy, but
      demonstrate the need and underline the importance of further randomized clinical
      trials. Abdominopelvic irradiation following staging laparotomy is not
      recommended for advanced stages and has at the most limited benefit as
      consolidation therapy after successfully cytoreductive chemotherapy depending on
      the amount of residual tumor.

PMID- 7502227
TI  - [The initial results on the radiobiological comparability of continuous LDR
      irradiation and PDR irradiation using a guinea pig skin animal model].
AB  - AIMS: The classic continuous low dose rate (LDR) brachytherapy was very important
      in such cases with a higher risk of severe especially late radiation reactions.
      From clinical experiences and radiobiological considerations it is known, that
      the therapeutic ratio of LDR is higher than HDR. Another way to combine the
      therapeutic ratio of LDR and the possibility of optimisation is the use of pulse
      dose rate (PDR) technique. The PDR-technique is a method, which can be compared
      with continuous LDR-therapy. PDR should have biological effects equivalent to
      conventional LDR. MATERIAL AND METHODS: We have tried to compare the classic
      continuous LDR-technique with 2 PDR-regimes by means of the guinea pig skin
      model. In this test series we involved 20 female animals with an initial weight
      of 400 to 500 g. We compared radiation reactions of following regimes: 1.
      Continuous LDR regimen with a cobalt-60 source with an activity of 5.5 mCi 30 Gy
      in 60 hours. 2. PDR regimen 0.5 Gy hourly, pulse length minimal 10 minutes, 30 Gy
      in 60 hours with an Ir-192 source with an activity of nearly 40 mCi. 3. PDR
      regimen 0.8 Gy hourly with 9 hours night break (10.00 p. m. to 7.00 a. m.). The
      radiation reaction was controlled by the help of an evaluation table in which the
      criteria of radiation reaction were classified according to the degree of
      seriousness. The observation time is now minimal 14 and maximal 24 months.
      RESULTS: The findings shows a significant coincidence of early and late radiation
      reactions of the skin fields irradiated with the continuous LDR-technique and
      fields irradiated with the PDR-technique. There was not a difference of the
      radiation reactions between PDR-irradiation with and without night break.
      CONCLUSIONS: Generally it is possible to compare the radiation reactions of PDR
      irradiation and the classic continuous LDR-brachytherapy. It is also possible to
      use a PDR-regimen with a night break of 9 hours. But results must be calculated
      for each tissue of interest, in our test consequently for guinea pig skin.

PMID- 7502228
TI  - [The results of the radiotherapy of brain metastases in patients at an advanced
      age].
AB  - BACKGROUND: To evaluate which patients older than 70 years will benefit by
      radiotherapy for their brain metastases. PATIENTS AND METHODS: The data of 35
      patients in this age-group who were treated between 1983 and 1994 were
      retrospectively analyzed. All patients were previously untreated and received a
      whole-brain irradiation and concomitantly corticosteroids. The median total dose
      was 30 Gy (fractionation: 10 times 3 Gy in 2 weeks). Six patients each received
      lower or higher total doses with 50.4 Gy at maximum. RESULTS: Six patients failed
      to complete their prescribed treatment (17%). The median survival of all patients
      who completed their radiotherapy course was 67 days only. Patients with
      extracerebral metastases had a median survival of 31 days. Survival was not
      dependent on total dose of radiotherapy. In 56% of all cases the general
      condition of the patients improved or remained stable at a high level. Karnofsky
      performance status was the most important prognostic factor. CONCLUSIONS:
      Advanced age is an unfavourable prognostic factor. Only patients in good general
      condition without extracerebral metastases had survival times which justify
      radiotherapy for their brain metastases. It seems to be extremely doubtful
      whether the other cases surviving 1 to 2 months should undergo radiotherapy. In
      each case a short and easily tolerable course of radiotherapy should be
      preferred.

PMID- 7502229
TI  - [10 years' experiences with an innovative irradiation technic in breast
      carcinoma. An analysis of the late sequelae in normal tissue].
AB  - PURPOSE: In "high risk" breast cancer patients radio- and chemotherapy or
      hormonal strategies are applied after mastectomy. To reduce the risk of hot spots
      we developed an innovative irradiation technique using only 2 portals to
      encompass the chest wall and the regional lymph node areas. PATIENTS AND METHODS:
      In a retrospective analysis we evaluated 131 patients concerning late normal
      tissue reactions. We compared one group of combined treated patients (radio- and
      chemotherapy) with women who only had irradiation after surgery. RESULTS: The
      most frequent findings are telangiectasia in the chest wall (electron portal):
      grade 3 (1.5%), grade 2 (4.6%), grade 1 (35.8%), 58% no telangiectasia. A
      moderate lymphoedema of the arm was seen in 4.5%. There was no statistically
      significant difference between the 2 groups. CONCLUSION: Our treatment concept
      allows simultaneous application of radio- and chemotherapy without enhancement of
      late normal tissue reactions.

PMID- 7502231
TI  - The role of adjuvant therapy in the treatment of breast cancer.

PMID- 7502230
TI  - Prophylactic irradiation of para-aortic lymph nodes in carcinoma of the uterine
      cervix. A prospective randomized study.
AB  - PURPOSE: For assessment of the advantages and side effects of para-aortic lymph
      nodes irradiation under the evaluation by computer tomography, a prospective
      randomized study was started in 1986. The results for survival, local control and
      late complications are presented in the following. PATIENTS AND METHODS: From
      November 1986 to October 1990, 93 patients with cervical carcinoma were randomly
      allocated for treatment with either pelvic irradiation (pelvic group) or pelvic
      plus para-aortic lymph nodes irradiation (para-aortic group). Thirty-six patients
      underwent external irradiation and intracavitary therapy (RT arm) and 57
      patients, extended radical hysterectomy and external irradiation (OP-RT arm).
      Para-aortic lymph nodes irradiation delivered 45 Gy in 1.8 Gy per day for 5 days
      per week through anterior-posterior fields. RESULTS: The 3-year cause specific
      survival rates were para-aortic group: 57% and pelvic group: 89% in RT arm group,
      and para-aortic group: 70% and pelvic group: 86% in OP-RT arm group. Differences
      for the 2 groups in each treatment arm were not significant. In pelvic failure,
      para-aortic lymph nodes metastases and distant metastases showed no statistically
      significant differences for the 2 groups in each treatment arm. In the para
      aortic group, complications were more frequent than in the pelvic group (13/45
      vs. 2/48, p < 0.025). As an enteric complication ileus was found in 7% (3/45) of
      the para-aortic group while 2% (1/48) in the pelvic group. Compression fractures
      of the lumber vertebral body were apparent in 9% (4/45) and 0%, respectively.
      CONCLUSION: Routine para-aortic lymph nodes irradiation delivered through
      anterior-posterior fields for high risk patients with cervical carcinoma is of
      limited value occurring to the high incidence of late complications and this
      treatment fails to improve no survival rates.

PMID- 7502232
TI  - [Adjuvant chemotherapy after radical cystectomy in bladder carcinoma].

PMID- 7502233
TI  - [The effect of the irradiation technic on the success of preoperative
      radiotherapy in rectal carcinoma: the results of the Stockholm-I and -II
      studies].

PMID- 7502234
TI  - [The optimization of radiotherapy in patients with cerebral chordomas].

PMID- 7502235
TI  - [The documentation and publishing of radiotherapy side effects. A workshop
      report].

PMID- 7502236
TI  - Platelet-derived growth factor receptor alpha subunit deleted Patch mouse
      exhibits severe cardiovascular dysmorphogenesis.
AB  - Patch (Ph) mice, whose platelet-derived growth factor receptor alpha subunit
      (alpha PDGFR) gene has been deleted, have been used to elucidate requirements for
      alpha PDGFR for normal murine development. In this report we evaluate the role of
      alpha PDGFR in cardiovascular development by using in situ hybridization to
      follow the changing pattern of alpha PDGFR expression in cardiovascular tissues
      after embryonic day 13, and comparing this pattern with the pattern of
      cardiovascular defects observed in homozygous Ph mutants. Both mesodermally
      derived and neural crest-derived components of the cardiovascular system are
      severely dysmorphic in Ph/Ph embryos and those structures most severely affected
      are those that normally express alpha PDGFR mRNA at the highest levels and for
      the longest duration. Ph/Ph vessels appear to be lined with a normal endothelium,
      but contain a reduced number of smooth muscle cells and are fragile during
      processing for histology. The myocardium is thin, the heart is small and
      dysmorphic, the valves are malformed, and the interventricular and interatrial
      septa of the heart are defective. In the outflow tract, the spectrum of defects
      includes both persistent truncus arteriosus and double outlet right ventricle.
      This pattern of abnormalities is consistent with the hypothesis that deletion of
      alpha PDGFR results in a functional ablation of cranial neural crest cells, and
      that mesodermally derived components of the vascular system also require alpha
      PDGFR.

PMID- 7502237
TI  - Defining the susceptible period of developmental toxicity for the AT1-selective
      angiotensin II receptor antagonist losartan in rats.
AB  - Previous developmental and reproductive toxicity studies conducted in rats with
      Losartan, a potent AT1 subtype selective angiotensin II receptor antagonist,
      noted treatment-related effects on the pups of dams treated beyond the second
      trimester through lactation, as demonstrated by increases in pre- and postweaning
      pup deaths and decreased pup body weights [Spence et al. (1995) Teratology 51:000
      000]. The studies presented here were designed to define the critical period for
      the induction of neonatal toxicity and to examine the effects of Losartan on
      kidney development when the drug is administered to the dam beyond the second
      trimester through lactation. In a developmental toxicity study with postweaning
      evaluation, pregnant rats were administered 5, 20, and 100 mg Losartan/kg/day on
      gestation days 6 through 15 (GD 6-15). There were no adverse effects on the F1
      generation as assessed by mortality, clinical signs, weight gain, external
      examinations, developmental signs, behavioral tests, and gross or microscopic
      examination of the kidney. In a fostering/cross-fostering study, pregnant rats
      were administered 100 mg Losartan/kg/day on GD 15 through lactation day 20 (LD
      20). Following delivery, pups from dams treated with Losartan were fostered to
      control dams, pups from control dams were fostered to Losartan-treated dams, and
      pups were also fostered to dams within the same group. Maternal exposure to
      Losartan during lactation increased the incidence of pup deaths on postnatal days
      1-3 (PND 1-3), caused decreased pup weights on PND 7, and decreased performance
      in the auditory startle test in females and increased performance on the second
      swim maze test in males, relative to controls. Maternal exposure to Losartan
      during gestation was associated with decreased pup weight on PND 21 and effects
      observed on male performance in the swim maze test. Treatment during gestation
      was also associated with decreased pup cardiac weight as well as drug-induced
      histopathological changes of the kidneys from F1 pups, including medial
      hypertrophy of intracortical arterioles and dilatation of the renal pelvis. While
      the cardiac and renal vascular effects disappeared with time, significant renal
      lesions were still evident by PND 90. In a late-gestation/lactation study with
      renal evaluation, pregnant rats were administered 0.5, 1.0, 5.0, 20, and 100 mg
      Losartan/kg/day on GD 15-LD 20. Maternal toxicity was evident as decreased body
      weight gain in the 100 mg Losartan/kg/day group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502238
TI  - Evaluation of the reproductive and developmental toxicity of the AT1-selective
      angiotensin II receptor antagonist losartan in rats.
AB  - Losartan, an AT1-selective angiotensin II receptor antagonist, was evaluated in
      female rats for effects on fertility, reproduction, and perinatal and postnatal
      development. In a range-finding study, pregnant rats were treated orally from
      gestation days 6-17 (GD 6-17) with doses of 25, 75, 150, 225, and 300 mg
      Losartan/kg/day. There were treatment-related decreases in maternal body weight
      gain, slight treatment-related decreases in hemoglobin concentration, and slight
      treatment-related increases in serum urea nitrogen in the 225 and 300 mg/kg/day
      groups. In a fertility study, female rats were treated for 15 days prior to
      mating, during mating, and GD 0-19 with doses of 25, 100, and 300 mg
      Losartan/kg/day. The initial dose of 300 mg/kg/day was lowered to 200 mg/kg/day
      at the start of mating due to excessive body weight loss during the premating
      treatment interval. There were no treatment-related effects on reproductive
      performance, mating, or fertility indices in the F0 generation. There was no
      evidence of treatment-related or dose-related fetal malformations. However,
      decreased F1 pup body weights were observed in all drug-treated groups. In the
      100 and 300/200 mg/kg/day groups there were treatment-related increases in F1 pup
      mortality and alterations in the pattern of postweaning body weight gains. There
      was also a delay in developmental signs in the 100 and 300/200 mg/kg/day groups,
      which were likely secondary to the decreased weight of the pups in these groups.
      In a developmental toxicity study, pregnant rats were administered 50, 100, and
      200 mg Losartan/kg/day on GD 6-17. There was no evidence of developmental
      toxicity in any dose group. Maternal toxicity was evident in the 200 mg/kg/day
      group as a treatment-related decrease in body weight gain during gestation. In a
      late-gestation/lactation study, pregnant rats were administered 10, 25, and 100
      mg Losartan/kg/day on GD 15 through lactation day 20 (LD 20). There were
      treatment-related decreases in maternal body weight gain during gestation and
      lactation in the 100 mg/kg/day group. Decreased pup weights were noted in all
      dose groups, and pre- and postweaning pup deaths were observed in the high dose
      group which were comparable to those observed in the female fertility study. The
      lack of fetal body weight effects at 100 mg Losartan/kg/day in the developmental
      toxicity study, with treatment ending on GD 17, indicates that adverse effects
      observed in the F1 generation in the fertility and late-gestation/lactation
      studies were due to exposure during late gestation and/or lactation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7502239
TI  - Teratogenicity of low doses of all-trans retinoic acid in presomite mouse
      embryos.
AB  - This study was designed to examine the developmental dose response for all-trans
      retinoic acid (TRA) administered at presomite stages in mouse embryos. Previous
      studies using hamsters [Shenefelt (1972) Teratology 5:103-118] have shown that
      developmental stages corresponding to those present early on gestational day (GD)
      7 in mice are most sensitive to retinoid-induced teratogenesis. Our preliminary
      studies showed that at this treatment time, gavage dosages of 7.5 mg/kg maternal
      body weight administered to C57B1/6N mice, an inbred strain, resulted in severe
      craniofacial malformations representing the holoprosencephaly, aprosencephaly
      spectrum. Additionally, in an outbred mouse strain, CD-1, exencephaly was induced
      by dosages of 2.5 mg/kg TRA and above. Readily detectable abnormalities of the
      eyes, including anophthalmia and severe microphthalmia and iridial colobomata,
      were induced by even lower doses cf TRA in the C57B1/6N strain. Incidences of
      micro/anophthalamia were 6.7%, 8.1%, 12.9%, and 32.4% at 0, 0.313, 0.625, and
      1.25 mg/kg, respectively. The dosages required to induce significant incidences
      of exencephaly (2.5 mg/kg) and severe ocular abnormalities (1.25 mg/kg) on GD 7
      in mice are approximately 50-100-fold less than those that are commonly used to
      examine the teratogenicity of this compound at later developmental stages in this
      species. The trend toward an increase in the incidence of severe ocular
      malformations at the lowest dose examined and the fact that subtle ocular
      malformations were not taken into account for this study suggest that even lower
      dosages may be effective.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502240
TI  - Aspirin-alcohol interaction in the production of cleft palate and limb
      malformations in the TO mouse.
AB  - Our objective in the present study was to determine the effects of alcohol on
      stages when the limb buds and renal primordia develop in the TO mouse and to see
      if aspirin pretreatment would prevent these organ systems from being malformed as
      was shown by Randall et al. ('91) in the C57 mice. On one of days 9-12 of
      gestation, groups of TO mice were injected intraperitoneally (IP) with a single
      dose of 200 mg/kg of aspirin, or a proportionate volume of physiological saline.
      An hour later, half of the aspirin-treated animals received a single dose of 0.03
      ml/g of freshly prepared 25% (v/v) solution of absolute alcohol and the other
      half received a proportionate volume of saline. Half of the saline-treated
      animals received a single dose of 0.03 ml/g of saline or a proportionate volume
      of alcohol solution. All animals were killed on day 18 of gestation. Alcohol
      significantly increased embryonic resorption and caused remarkable intrauterine
      growth retardation (IUGR). It also induced arched palate, cleft palate and
      deformities of the digits with haematomas in a modest number of embryos. Aspirin
      alone did not have any teratogenic effects. Pretreatment with aspirin
      significantly augmented alcohol-induced resorption, IUGR, cleft palate and
      digital malformations associated with haematomas. Chronological observations on
      the development of the treated limbs showed the occurrence of vascular stasis,
      haematomas, edema and cell death at early stages. Subsequently, digital rays were
      either destroyed (ectrodactyly) or remained hypoplastic (brachydactyly). It
      appears that limb development in the aspirin- and alcohol-treated TO mouse
      embryos is largely affected by vascular disruption. These data provide further
      evidence to our earlier observation that alcohol and aspirin interact in the
      production of malformations and that the teratogenic effects of alcohol in the TO
      mouse are possibly not mediated via treatment related prostaglandin elevation.

PMID- 7502241
TI  - Programmed cell death and N-acetoxy-2-acetylaminofluorene-induced apoptosis in
      the rat embryo.
AB  - N-acetoxy-2-acetylaminofluorene (N-Ac-AAF) is an alkylating agent that forms DNA
      adducts at C-8 in guanine and causes single strand breaks. It has previously been
      shown to be embryotoxic, but the mechanisms by which it causes abnormal
      development have not been investigated. Previous studies have indicated that
      other DNA alkylating agents cause cell death during embryonic development
      although the types of cell death were not characterized. Using a whole embryo
      culture system, gestation day 10 rat embryos were exposed to several
      concentrations (5, 50, and 200 micrograms/ml) of N-Ac-AAF. At several time points
      after exposure was begun (5, 10, and 24 hours), the embryos were removed from
      culture and examined to identify location, type and quantity of cell death,
      relative to programmed cell death observed in control embryos. Vital staining
      with Nile blue sulphate revealed that the location of N-Ac-AAF-induced cell death
      included the forebrain region, tail, and areas of programmed cell death.
      Examination of tissue sections from both control and treated embryos indicated
      that the location of apoptotic cell death revealed by in situ DNA nick end
      labelling was generally consistent with the cell death pattern observed by vital
      staining of whole embryos. Agarose gel analyses indicated that all concentrations
      of N-Ac-AAF caused DNA fragmentation, and quantification demonstrated a dose
      response. Examination of treated embryos (50 and 200 micrograms/ml) by
      transmission electron microscopy revealed that, by 5 hours after exposure, cells
      with classic, ultrastructural features of apoptosis were present. In conclusion,
      multiple methods have all indicated that, regardless of exposure level, apoptosis
      was the predominant form of cell death. Because apoptosis also occurs in
      developmental cell death, it is possible that apoptosis induced by N-Ac-AAF is
      due to an alteration in cell fate via premature or ectopic induction of the cell
      death program.

PMID- 7502242
TI  - Utility of fluorescence microscopy in embryonic/fetal topographical analysis.
AB  - For topographical analysis of developing embryos, investigators typically rely on
      scanning electron microscopy (SEM) to provide the surface detail not attainable
      with light microscopy. SEM is an expensive and time-consuming technique, however,
      and the preparation procedure may alter morphology and leave the specimen
      friable. We report that by using a high-resolution compound epifluorescence
      microscope with inexpensive low-power objectives and the fluorochrome acridine
      orange, we were able to obtain surface images of fixed or fresh whole rat embryos
      and fetal palates of considerably greater topographical detail than those
      obtained using routine light microscopy. Indeed the resulting high-resolution
      images afford not only superior qualitative documentation of morphological
      observations, but the capability for detailed morphometry via digitization and
      computer-assisted image analysis.

PMID- 7502243
TI  - Teratogen update: carcinogenesis and teratogenesis associated with exposure to
      diethylstilbestrol (DES) in utero.
AB  - Exposure of the human fetus to physician-prescribed diethylstilbestrol and other
      synthetic estrogens (collectively referred to as "DES") led to an important
      iatrogenic epidemic. In the United States alone, at least four million fetuses
      and their mothers had a substantial exposure to these estrogens now known to be
      mild carcinogens and potent teratogens. Mothers exposed to DES may have a
      somewhat higher risk of breast cancer than women who were not exposed. The
      sequelae of in utero exposure of daughters include clear cell adenocarcinoma of
      the vagina and cervix, various gross anomalies of the genital tract that are
      associated with adverse outcomes of pregnancy, vaginal adenosis and other vaginal
      epithelial changes, and other possible health effects that have not yet been
      fully evaluated. Among sons exposed in utero to DES, no increase in the incidence
      of any cancer has been reported, but several anomalies of the genital tract have
      been described, and it is possible that some social behaviors are modified.
      Although the grandchildren of the DES-exposed daughters and sons have not been
      shown to have any abnormalities, some of them have been the products of short
      gestations. Future research, being funded by the National Cancer Institute, will
      permit monitoring of the DES-exposed population to determine whether any other
      abnormalities will become apparent in them.

PMID- 7502244
TI  - [Patients with ENT problems].

PMID- 7502245
TI  - [Otitis externa and cerumen obturans].
AB  - Otitis externa and cerumen obturans are two of the most frequently encountered
      disturbances in the external auditory canal. Both conditions can lead to hearing
      loss due to reduced sound transmission. Other symptoms include ear pressure, pain
      and secretion. Acute otitis externa occurs frequently during the swimming season.
      The main symptoms are local pain and secretion. Treatment consists of careful and
      frequent cleaning and application of topical medication to the outer ear canal
      and prescription of medication against pain. Systemic antibiotics are only rarely
      necessary and are indicated if perichondritis or lymphadenitis are present.
      Chronic otitis externa is often caused by eczema of the outer ear canal.
      Allergies, systemic diseases, such as diabetes mellitus, and manipulation by the
      patient must be ruled out. Therapy includes the application of topical steroid
      solutions. The natural pH of the skin can be reestablished by use of diluted
      acetic acid solutions. Blockage of the outer ear canal by cerumen [cerumen
      obturans] can bring the patient to the office because of sudden hearing loss.
      After cleaning of the ear canal, a screening hearing test should be performed to
      assure that the problem has been resolved.

PMID- 7502246
TI  - [Tinnitus].
AB  - Tinnitus rarely can be cured. The patient, however, needs help in order to avoid
      countless ineffective treatments and considerable costs. The paper deals with the
      management of decompensated tinnitus. It outlines the problems and possible means
      for guidance of the patient toward acceptance of the handicap.

PMID- 7502247
TI  - [Dizziness from a neuro-otological viewpoint].
AB  - The symptom of vertigo can be due to many different causes. Differential
      diagnosis will be discussed primarily from a neuro-otologic point of view.
      Vertigo can be thought of as a subjective disturbance of the integration of
      different sensory inputs. The history and subjective characterisation of vertigo
      often provide enough information for initial differential diagnosis and
      recommendation for a specific evaluation. The evaluation includes simple tests of
      posture and gait, tests of ocular motility, and examination of nystagmus.
      Instability and nystagmus towards a specific direction point to a vestibular
      disorder, especially if the nystagmus is suppressed by optical fixation. The most
      common causes of a vestibular disorder are benign paroxysmal positional vertigo
      (BPPV), a sudden vestibular loss (or vestibular neuritis), and Meniere's disease.
      These three diseases are discussed briefly.

PMID- 7502249
TI  - [Current status of diagnosis and therapy of allergic rhinitis].
AB  - A general rise in the occurrence of allergies has led to an increasing number of
      ENT consultations due to allergic rhinitis. The prevalence of allergic rhinitis
      amounts to 10 to 16% in Central Europe with a tendency to be on the rise.
      Etiological factors include an unhealthy lifestyle (stress), dietary habits,
      exposure to environmental pollutants, and genetic predisposition. The diagnostic
      work-up consists of a specific history of allergies, a general ENT examination,
      provocation tests of allergens such as skin reaction tests, and laboratory tests.
      Treatment includes avoidance of allergens, induction of hyposensitivity,
      symptomatic drug treatment, and acupuncture.

PMID- 7502248
TI  - [Disorders of the sense of smell and taste].
AB  - Disorders of olfaction and taste are infrequent, but a complete loss of smell or
      taste reduces the quality of life significantly. The sensitivity of human
      olfaction is remarkable, even for specific stimuli: Just a few molecules are
      enough to induce the correct identification of sterilised and ultraheated milk.
      Olfaction and taste are called 'chemical senses' because in both cases the
      adequate stimulus consists of molecules that bind to receptors of the sensory
      cells. The perceptions of smell and taste are often combined. Taste
      differentiates only four qualities: sweet, sour, salty, and bitter. The typical
      flavor of food or drink is detected by olfaction. Disturbances of olfaction can
      be due to respiratory disorders such as nasal polyps, a deviation of the nasal
      septum or chronic sinusitis. Such conditions can reduce airflow through the
      olfactory cleft at the roof of the nasal cavity. They can be corrected by modern
      endoscopic surgery of the nose. Epithelial disorders involving the sensory cells
      are most often caused by viral infections (influenza-anosmia) or toxic
      destruction of the sensory epithelium (solvents or gases). Epithelial disorders
      can be cured only rarely by any treatment. Corticosteroids, zinc, and vitamin A
      are tried frequently. Neural disorders occur after frontobasal trauma and during
      neurological diseases such as Parkinson's or Alzheimer's disease. Disorders of
      olfaction can be an early sign of such neurological diseases and sophisticated
      examination of this sense can contribute to their early diagnosis. However, no
      specific treatments have yet been identified. Disorders of taste can be due to
      toxic, chemical or inflammatory damage to the sensory cells of the
      tongue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502251
TI  - [Pharyngitis and its various clinical manifestations].
AB  - Pharyngitis is one of the most frequent diseases of the upper aero-digestive
      tract. The different kinds of inflammation of the pharynx are described with
      regard to etiology, clinical appearance and therapy.

PMID- 7502252
TI  - [Dysphagia].
AB  - The otolaryngologist has a central role in the detailed examination for dysphagia
      with its vast differential diagnosis. The carefully elicited medical history and
      a deliberately focused physical examination are the most important tools to
      disclose the basis of the dysphagia. Nonspecific blind treatment of dysphagia is
      obsolete.

PMID- 7502250
TI  - [Sinusitis, current diagnostic and therapeutic possibilities].
AB  - Important progress in the management of sinusitis has been made during the past
      decade. Diagnosis has been refined by the general use of endoscopic examinations
      of the nose and the CT scan. Knowledge of the pathophysiology of sinusitis has
      been improved by the systematic use of the examinations. As a consequence, the
      treatment of sinusitis, particularly of chronic sinusitis, has been
      revolutionized by the introduction of functional, endoscopically controlled
      surgery of the paranasal sinus. This form of endonasal microsurgery permits the
      treatment of chronic sinusitis without the need of radical surgery or external
      skin incisions.

PMID- 7502253
TI  - [Hoarseness].
AB  - Hoarseness is a cardinal symptom of laryngeal disease. It is a disturbance of the
      normal voice pitch that can be evaluated acoustically using the 'RBH scale' [R
      for roughness, B for breathiness, H for hoarseness]. Hoarseness lasting longer
      than three weeks or recurring must be evaluated by an ENT specialist or a
      phoniatrist. Causes of hoarseness include functional disorders of the voice,
      inflammation of the larynx, secondary changes of the vocal folds, polyps, cysts,
      edema, papillomas, tumors, trauma, or palsies of the vocal cords due to different
      reasons. Early diagnosis of malignant laryngeal tumors is a prerequisite for
      preserving voice quality. Functional disorders and unilateral palsies of the
      vocal folds are treated by logopedists. The therapy of choice for inflammations
      is relief of symptoms, and surgery is employed for organic lesions.

PMID- 7502254
TI  - [Diagnostic procedures in obscure cervical nodes in adults].
AB  - Cervical masses in adult patients should be regarded as metastatic until proven
      otherwise. Work-up must therefore begin with a thorough search for a possible
      primary cancer. 90% of all head and neck primaries that present with a cervical
      mass are located in the oral cavity, pharynx or larynx. Pain [particularly
      otalgia], dysphagia, nasal obstruction, unilateral hearing loss, and hoarseness
      are the most common key symptoms of these tumors. Cancer cannot always be ruled
      out, even with regression of symptoms following antibiotic treatment or normal
      laboratory findings. If no primary lesion is found, then fine-needle aspiration
      biopsy of the neck mass is indicated. Only if fine-needle aspiration biopsy fails
      to come up with a diagnosis, should open [whenever possible excisional] biopsy be
      performed.

PMID- 7502255
TI  - [Tumors in otorhinolaryngological surgery].
AB  - The most frequent tumors of the head and neck region are squamous cell carcinomas
      located within the oro- and hypopharynx [37%] or the larynx [36%]. They are
      clinically associated with chronic hoarseness dysphagia and swelling of the
      lateral neck. The general physician should pay attention to these initial
      symptoms, so that most of the tumors can be found noninvasively and at an early
      stage. Palpation and inspection are sensitive tools for the primary examination
      of many types of head and neck cancer. In addition, flexible or rigid endoscopy
      and high-resolution imaging are useful. Modern treatment of early head and neck
      cancer can be minimally invasive. The laser technique, new biocompatible implants
      for the reconstruction of postoperative defects and progress in radiotherapy
      complete the classic management of head and neck cancer.

PMID- 7502256
TI  - [Salivary gland diseases].
AB  - Only about 1% of head and neck tumors are neoplasms of the salivary glands. The
      majority [80%] of these tumors are benign. Pleomorphic adenomas, the most
      frequent benign tumors of the salivary glands, can transform into malignancy,
      especially after a long duration. Treatment of salivary gland tumors consists of
      complete surgical excision by a surgeon experienced in microsurgery of the facial
      nerve. Acute suppurative and viral sialadenitis is usually treated by the general
      practitioner either symptomatically or, if possible, specifically. Chronic
      sialadenitis, sialadenosis, Sjogren's syndrome, and Frey's syndrome often need
      long-term follow-up and medical treatment, which is also usually delivered by the
      general practitioner, after the diagnosis has been established. Trauma to the
      salivary gland with transsection of the duct or facial nerve needs immediate
      microsurgical repair by an otolaryngologist. Sialolithiasis is also treated
      surgically in most cases.

PMID- 7502257
TI  - [A joint community of donors and recipients. An interview with Prof. Felix J.
      Frey].

PMID- 7502258
TI  - [Management of patients with transplants in clinical practice].

PMID- 7502259
TI  - [Recurrence of diabetic disease following pancreas transplantation].
AB  - Type-I diabetes is considered an autoimmune disease, directed against pancreatic
      beta cells. Diabetes recurrence after pancreas transplantation is theoretically
      possible, and some cases have been reported after isotransplantation of segmental
      grafts in HLA-identical twins, where no rejection phenomenon is possible and
      where no immunosuppression was used. Diabetes recurrence has never been observed
      in a cadaveric allograft recipient, probably because immunosuppression
      efficiently blocks the autoimmune mechanism. Autoreactivity against beta cells
      exists life-long in type-I diabetes, and the immunosuppression used after
      transplantation becomes an advantage y preventing the recurrence of the disease.

PMID- 7502260
TI  - [Does the primary disease recur in kidney transplantation?].
AB  - Improved graft survival is accompanied by complications which interfere with the
      long-term function of the allograft. Recurrence of the primary renal disease in
      the graft is well recognized and is found in 10 to 20% of all recipients;
      however, graft loss due to recurrent disease is reported in less than 5% of all
      cases. The most frequent cause of recurrence is glomerulonephritis: Membrano
      proliferative GN type II, IgA nephritis and focal sclerosis are frequently
      observed. Among metabolic disorders linked to graft disease, diabetic nephropathy
      has to be mentioned first. Primary oxalosis is a rare disorder, but it is related
      to a very high risk of recurrent disease in the transplant. Combined kidney-liver
      transplantation seems to offer a valuable alternative for these patients. The
      high risk of recurrence of certain diseases, i.e. membrano-proliferative GN type
      II, focal-segmental glomerulosclerosis, primary oxalosis, should prevent living
      donation. In addition, there are some reports suggesting that living-related
      donation might increase the recurrence rate of hemolytic-uremic syndrome,
      membranous GN and Schonlein-Henoch purpura. Recurrent disease might not only
      affect the outcome of the transplant, but can provide insight into the nature and
      pathogenesis of the primary disease. Currently there are no conclusive reports
      indicating that chronic immunosuppression, especially cyclosporin-A treatment,
      reduces recurrence rates; however the clinical course might be ameliorated.

PMID- 7502261
TI  - [Does the primary disease recur following liver transplantation?].
AB  - A number of underlying diseases may recur after orthotopic liver transplantation.
      While the recurrence of cholestatic diseases such as primary biliary cirrhosis
      and primary sclerosing cholangitis is still debated, and occurs, if at all,
      rarely and late after transplantation, the chronic viral hepatitides and the
      liver tumors recur frequently and in general early after grafting. Except for
      hepatitis B and tumor recurrence, recurrent diseases have rarely an impact on
      survival and/or quality of life in medium terms. The frequency of the often fatal
      hepatitis-B reinfection can be minimized by passive immunoprophylaxis and
      appropriate patient selection, that of tumor recurrence by thorough patient
      selection. Relapses occur only rarely after transplantation for post-alcoholic
      cirrhosis, provided stringent selection criteria, including a period of
      documented sobriety > or = 6 month prior to transplantation, are applied. Thus,
      except for chronic hepatitis B with ongoing viral replication and most liver
      cancers, the possibility of recurrent disease is not a contraindication to liver
      transplantation.

PMID- 7502262
TI  - [Does heart disease recur following heart transplantation?].
AB  - The long follow-up after heart transplantation is influenced by the occurrence of
      graft-coronary artery disease. This complication remains a diagnostic, prognostic
      and therapeutical dilemma. This short review gives an insight into the principal
      aspects concerning this complication.

PMID- 7502263
TI  - [Liver transplantation: results with living donors].
AB  - Liver transplantation with harvesting of the graft from living related donors is
      a new technique. It was introduced in 1989 as a response to the shortage of donor
      organs for small children in the west and to the complete absence of such organs
      in Japan. Results have been as good as for transplantation from cadaveric donors.
      Our experience confirms these results and shows that this technique, so far
      restricted to small children in most cases, can also be extended to adults in
      selected cases.

PMID- 7502264
TI  - [Follow-up care of living kidney donors].
AB  - The follow-up of living kidney donors demands medical as well as psychological
      competence. In the postoperative period, attention focuses on pain management,
      early detection of wound complications and the prophylaxis of thromboembolism.
      Regular visits of the donor who may easily feel neglected should be as much part
      of the transplant team's post-operative routine as visits of the recipient. The
      later phase of recovery emphasizes strengthening abdominal wall and lumbar
      muscles as well as the gradual increase of physical activity. Long-term follow-up
      focuses on the early detection of arterial hypertension and proteinuria.
      Antihypertensive therapy in nephrectomized donors should include an ACE inhibitor
      or an angiotensin-II antagonist. In Switzerland, the long-term course after
      living donation is prospectively monitored by the Swiss Registry for Living
      Donors founded in 1993. The registry is responsible for the regular timing of
      follow-up examinations and assures transparency of the origin of the kidneys used
      for living donation in Switzerland. The registry heavily relies on the
      collaboration of the donor's family physicians.

PMID- 7502265
TI  - [Advantages and disadvantages of combination kidney and pancreas
      transplantation].
AB  - Simultaneous kidney-pancreas transplantation represents an established method for
      the treatment of the diabetic patient with advanced renal failure. Continuous
      improvements of the surgical technique and of the immunosuppressive protocols
      resulted in 1-year graft survivals of the pancreas and the kidney of 75% and 85%,
      respectively. Currently the preferred surgical procedure is represented by the
      bladder drainage technique with a side-to-side duodenocystostomy. An intensive
      immunosuppressive regimen consisting of antilymphocytic antibodies, cyclosporine,
      azathioprine and steroids is mandatory to prevent and to treat rejection
      episodes. Graft rejection usually affects both kidney and pancreas concurrently;
      however, rejection generally manifests itself more distinct in the kidney, where
      it can be recognized and diagnosed much easier than in the pancreas. Simultaneous
      kidney-pancreas transplantation ensures normoglycaemia without the addition of
      exogenous insulin. Thereby, a substantial improvement in the quality of life can
      be attained. Furthermore, the transplantation of the pancreas leads to a
      stabilization of the neuropathy with a tendency towards improvement and
      effectively prevents the development of diabetic nephropathy in the
      simultaneously transplanted kidney. But no clear advantage has been shown for
      other diabetic complications like proliferative retinopathy and nephropathy.
      Compared to the transplantation of a kidney alone, one has to take into
      consideration a modest increase in patient morbidity due to the additional
      transplantation of the pancreas and to the more pronounced immunosuppressive
      therapy.

PMID- 7502266
TI  - [Management of children and adolescents with kidney transplantation].
AB  - Successful renal transplantation is widely accepted as the treatment of choice
      for end-stage renal failure in infants, children and adolescents. The major
      issues currently requiring consideration when contemplating renal transplantation
      in the mentioned patients are: primary renal disease, psychosocial status, life
      related versus cadaver donor allograft, optimal immunosuppressive regimen
      including cyclosporine, and maximization of growth and pubertal development. In
      transplanted adolescents, noncompliance is now a major problem, ranking only
      second to rejection as a cause of graft loss.

PMID- 7502267
TI  - [Sense and nonsense in infection prevention following organ transplantation].
AB  - Incidence and severity of infectious complications in solid-organ transplant
      recipients depend on the epidemiological exposure of the patients to infectious
      agents and the degree of immunosuppression. The timetable for the occurrence of
      infections reflects this interaction: up to one month after transplantation,
      patients suffer from infections related to the surgical procedure. Prevention is
      provided by careful surgical technique and perioperative antibiotics. One to six
      months after transplantation is the critical period for severe opportunistic
      infections: herpes viruses, fungi, mycobacteria and protozoal infections.
      Cytomegalovirus (CMV) are by far the most important source of morbidity and
      mortality. Various preventive strategies for CMV disease are critically reviewed;
      at present, pre-emptive therapy is our choice. Finally, we discuss prophylaxis of
      specific infections due to toxoplasma, P. carinii and M. tuberculosis. The value
      of local experiences (epidemiological exposures of patients, immunosuppressive
      regimes and antirejection therapy) for the choice of preventive strategies cannot
      be overemphasized.

PMID- 7502268
TI  - [When should the family physician contact the cardiological transplantation
      team?].
AB  - End stage heart failure has a poor prognosis and may be treated by cardiac
      transplantation, which offers these seriously sick patients a good chance of
      survival with an usually outstanding quality of life as compared to the
      preoperative state. The indication for heart transplant depends on hemodynamic
      and symptomatic evaluation as well as functional values. Spiro-ergometric
      assessment of peak oxygen consumption is used by an increasing number of cardiac
      transplant centres in order to achieve helpful data considering the ideal timing
      of transplantation. Correct assessment of the measured peak oxygen uptake is only
      suitable after the onset of tailored treatment of chronic heart failure;
      moreover, thinking about timing of heart transplantation, it is requested to be
      well informed on the spontaneous course of the underlying disease. Availability
      of appropriate organs depends on logistic factors, especially ABO blood group
      matching. In summary, these data may provide enough information whether and when
      patients should be scheduled for cardiac transplant. Ambulatory chronic heart
      failure clinics which are part of cardiac transplant programs are specialized
      institutions for the investigation of the underlying cardiac disease and for the
      institution of an appropriate therapy as well as for continuous observation of
      these patients. These chronic heart failure clinics are working very closely
      together with general practitioners and specialists involved in the treatment of
      these patients.

PMID- 7502269
TI  - Reduced thrombogenicity of type VI collagen as compared to type I collagen.
AB  - Type VI collagen has been recently identified as a major constituent of vascular
      subendothelium where it serves as a binding site for von Willebrand factor. The
      present study compares the functional characteristics of type VI collagen with
      those of type I collagen with respect to platelet aggregating and secretory
      activities. The differences between the two collagens in platelet aggregation and
      serotonin and beta-thromboglobulin release were found to be highly significant (p
      < 0.001, p < 0.0007, p < 0.005 respectively). Our results indicate that under in
      vitro conditions, type VI collagen stimulates a significantly lesser platelet
      activation and aggregation response than collagen I, suggesting that type VI
      collagen may play a role in vivo to limit the platelet thrombotic response
      following injury to the vascular subendothelium.

PMID- 7502270
TI  - Inhibition of red blood cell-induced platelet aggregation in whole blood by a
      nonionic surfactant, poloxamer 188 (RheothRx injection).
AB  - RheothRx Injection, an aqueous solution of a nonionic block copolymer (poloxamer
      188) formulated for intravenous administration, was investigated as an inhibitor
      of red blood cell (RBC)-induced platelet aggregation at plasma concentrations of
      0.05-5mgmL-1. Platelet aggregation was determined by measuring the fall in single
      platelet counts after mechanical agitation of 2mL aliquots of citrated whole
      blood in a 37 degrees C shaking waterbath. Inhibition of RBC-induced platelet
      aggregation of > 95% was observed for poloxamer 188 at a concentration of 1mgmL
      1, and 41% inhibition was observed at 0.05mgmL-1. Poloxamer 188 was observed to
      be a more effective inhibitor of RBC-induced platelet aggregation than 2
      chloradenosine (2-ClAd) or phosphoenolpyruvate/pyruvate kinase (PEP/PK). Studies
      using platelet rich plasma (PRP) showed that platelet aggregation could not be
      induced by shaking in the absence of RBC, though aggregation was induced by the
      addition of exogenous adenosine diphosphate (ADP). Poloxamer 188 did not inhibit
      ADP-induced platelet aggregation. We propose that poloxamer 188 protects RBC from
      mechanical trauma by non-specific adsorption of copolymer to the RBC surface (via
      the hydrophobic polyoxypropylene moiety), and that this effect prevents
      mechanical damage and hence leakage of ADP from RBC. RheothRx Injection has been
      shown to have value in the treatment of acute ischemic disorders such as
      myocardial infarction. The observation of significant inhibition of RBC-induced
      platelet aggregation at clinically relevant concentrations suggests that RheothRx
      Injection may have antithrombotic properties in vivo, and may therefore have
      potential not only in acute ischemia but also to prevent thrombosis within
      vascular prostheses or to prevent rethrombosis after angioplasty or
      endarterectomy.

PMID- 7502272
TI  - GLUT-3 (brain-type) glucose transporter polypeptides in human blood platelets.
AB  - Antiserum directed against a C-terminal peptide of the human GLUT-3 (brain type)
      equilibrative glucose transporter isoform reacted with polypeptides M(r) 46,000
      48,000 on immunoblots of human platelets. Photoirradiation of human platelets in
      the presence of 3H-cytochalasin B led to radiolabeling of polypeptides of
      identical mobility. This labeling was substantially reduced by preincubation the
      cells with 440 mM D-glucose, but not 440 mM L-glucose, consistent with glucose
      transporter function. Only traces of GLUT-1 (erythrocyte type) glucose
      transporter polypeptides were detected, and there was no evidence of GLUT-2
      (liver type) transporter on immunoblots of platelet proteins.

PMID- 7502271
TI  - Human placental tissue factor: protease susceptibility of extracellular and
      cytoplasmic domains.
AB  - We have examined the effects of seven proteases on human placental tissue factor
      in Triton X-100, focusing on extracellular and cytoplasmic domains recognized by
      monoclonal antibodies HTF1, C28 1.1, and C28 2.1. Plasmin produced peptides
      recognized on Western blots by C281.1 but not HTF1. None of the other proteases
      destroyed the extracellular epitope without also removing the cytoplasmic
      epitope, and both trypsin and chymotrypsin removed the cytoplasmic epitope with
      little effect on the extracellular domain. Proteinase K destroyed both epitopes,
      as did neutrophil elastase when used at a relatively high concentration. When
      digests were sampled over time and reconstituted with lipids for determination of
      tissue factor activity, only proteinase K consistently produced a loss in tissue
      factor activity at four hours. After 24 hr, other enzymes also decreased the
      recovered activity, with the order of effectiveness elastase > trypsin >
      chymotrypsin.

PMID- 7502273
TI  - Soluble fibrin in plasma before and after surgery for benign and malignant
      colorectal disease.
AB  - In a prospective study, plasma levels of soluble fibrin (SF) were assessed in 97
      patients with colorectal cancer immediately before and 1, 2, 7, and 90 days after
      surgery, 18 patients undergoing surgery for benign colorectal disease serving as
      controls. Age distribution, routine blood analysis, duration of surgery,
      perioperative blood loss and anaesthesia was similar in the two groups. SF was
      quantitated using a commercial enzyme-linked immunosorbent assay. The
      preoperative plasma level of SF was normal in cancer patients as a whole.
      However, patients with disseminated colorectal cancer had higher levels of SF
      preoperatively compared to patients with localized colorectal cancer (p < 0.01)
      and controls (p < 0.005). On days 1, 2, and 7 days postoperatively, a rather
      pronounced increase in plasma SF was observed in cancer patients as well as in
      the controls. Three months after surgery, plasma SF had normalized in controls
      and in patients undergoing curative cancer treatment. Postoperative deep venous
      thrombosis (DVT) was detected in 23% of the cancer patients by means of
      phlebography. The preoperative values of SF in these patients were higher
      compared to patients not developing DVT (p < 0.05). Patients with colon cancer
      displayed higher SF in plasma than patients with rectal cancer (p < 0.05).

PMID- 7502274
TI  - Lipid peroxidation products and changes in phospholipid composition induced by
      indobufen in diabetic platelets.
AB  - Indobufen is an antiaggregatory drug which first of all inhibits platelet
      aggregation by interfering with cyclooxygenase enzymes in platelets. We have
      investigated the influence of indobufen (200 mg twice daily for 10 days) on
      platelet lipid peroxidation and phospholipid metabolism in diabetic patients. The
      production of lipid peroxidation products was significantly lower after drug
      treatment. Indobufen administration, however, had no influence on the fatty acid
      composition of platelet phospholipids.

PMID- 7502275
TI  - Design and synthesis of thrombin substrates with modified kinetic parameters.
AB  - For the continuous registration of thrombin formation in plasma (1), selective
      thrombin substrates are required, that show moderate binding affinities (high Km)
      and low turnover numbers (low kcat). Previously we have used SQ68 (CH3O-CO-CH2-CO
      Aib-Arg-pNA) for this purpose. In order to find more substrates suitable for this
      application, we synthesized a series of 25 peptide p-nitroanilides. As lead
      structures SQ68 and S2238 (H-D-Phe-Pip-Arg-pNA) were used. By introduction of
      specific structure modifications we tried to alter the kinetic data in the
      required direction. The modifications were designed on basis of existing
      knowledge on the structure of the thrombin active-site and its surroundings. We
      indeed obtained a number of substrates with the kinetic constants in the desired
      range.

PMID- 7502276
TI  - The effects of gynaecological surgery on coagulation activation, fibrinolysis and
      fibrinolytic inhibitor in patients with and without ketorolac infusion.
AB  - The effects of gynaecological surgery on the fibrinolytic and inhibitor
      mechanisms were followed up for 24 h post-operatively in patients receiving a
      single dose of ketorolac infusion (n = 18) as compared with those not receiving
      ketorolac infusion (n = 11). A pre-operative state of lower mean t-PA activity
      and higher PAI-1 levels with increased platelet activation than that reported in
      normal subjects were observed in both groups of patients. Increased t-PA activity
      upon anaesthetic induction together with a decreased level at 24 h post-operation
      was seen in both groups. However, fibrinolytic 'shut-down' was not evident as
      significant increase in D-dimer levels was observed post-operatively, suggesting
      an enhanced lytic state concurrent with an enhanced activation of coagulation and
      diminished platelet activation although beta-TG remained above the normal level;
      plasmin from this enhanced lytic state affects platelet adhesion and cleaves
      platelet glycoprotein Ib thus inhibit release reaction. Ketorolac infusion
      elicited a significant response in PAI-1 activity within 24 h post-operation and
      this was not seen in the non-ketorolac group in spite of the rising trend by 24 h
      post-operation which did not achieve statistical significance. There were no
      statistical significant differences in blood loss and duration of surgery between
      the two groups of patients. Overall, both groups of patients showed similar
      haemostatic changes post-operatively for 24 h, a longer duration of post
      operative study would have revealed any subtle changes in the molecular markers
      of thrombosis which was not the objective of this study.

PMID- 7502277
TI  - Blood coagulability changes during exercise and its relationship with the
      anaerobic threshold.

PMID- 7502278
TI  - Successful heparin desensitization after heparin-induced anaphylactic shock.

PMID- 7502279
TI  - Purification of secreted platelet protease nexin I.

PMID- 7502280
TI  - "Cardioplegia on the contractile apparatus level": evaluation of a new concept
      for myocardial preservation in perfused pig hearts.
AB  - The concept of a reversible desensitization of the myocardial contractile
      apparatus for calcium by 2,3 Butanedione Monoxime (BDM) as a method to improve
      the myocardium's tolerance to cold ischemia was evaluated in normal pig hearts (n
      = 14). The results were compared to those obtained after application of
      Bretschneider's HTK cardioplegic solution. METHODS: Series I) After BDM treatment
      (concentrations: 0-30 mmol/L) the isometric force output and the intracellular
      calcium transients (measured using the FURA-2 ratio method) of electrically
      driven (1 Hz) isolated left-ventricular muscle strips excised from beating pig
      hearts (n = 14) were recorded simultaneously in order to analyse the mode of
      action of BDM; Series II) The cardioprotective effects of BDM (30 mmol/L) and
      Bretschneider's cardioplegic solution (HTK) were compared in a large-animal
      model: after "in situ perfusion" of pig hearts with either 2000 ml ice-cold BDM
      solution (30 mmol/L) (n = 7) or 2000 ml HTK (n = 7) the hearts were explanted and
      stored at 4 degrees C in the same solutions for up to 42 h. The contractile
      properties of muscle fibres, excised after storage periods of 8, 24, and 42 h
      from these hearts were analyzed in terms of isometric force development and
      isotonic shortening. 280 muscle fibres from 14 pigs were used for measurements.
      RESULTS: Series I) In pig myocardium a dose-dependent reduction of isometric
      force development was found after BDM application. The shape and the amplitude of
      the intracellular calcium transient were also affected by BDM. At 30 mmol/L BDM
      no force development could be elicited despite the presence of an intracellular
      calcium transient (amplitude < 70% of the control). Series II) Shortening,
      calcium transient, and force of left-ventricular muscle strips of pig myocardium
      excised after storage periods for up to 42 h showed complete recovery when BDM
      was applied. In contrast HTK perfusion allowed complete recovery of these
      parameters when the storage period did not exceed 6 hours. CONCLUSION: Under the
      given experimental conditions reversible desensitization of the contractile
      apparatus for calcium results in a considerable prolongation of the tolerance to
      cold ischemia in explanted pig hearts. The present study shows that the
      protective effects of BDM are not only present when isolate muscle fibres were
      stored (and the extracellular space is large) but also after storage of complete
      hearts in a solution in a solution containing BDM. Thus BDM may become a useful
      agent to enlarge the storage period of donor hearts in heart transplatation
      considerably.

PMID- 7502281
TI  - Antegrade versus retrograde crystalloid cardioplegia: perioperative assessment of
      cardiac energy metabolism by means of myocardial lactate measurement.
AB  - The effects of retrograde and antegrade delivery of cold St. Thomas' Hospital
      cardioplegia were evaluated and compared in 21 patients who underwent elective
      myocardial revascularization. The patients were randomly separated into two
      groups: the antegrade group (n = 10), and the retrograde group (n = 11). Cardiac
      energy metabolism was monitored by evaluation of arterial and coronary sinus (CS)
      lactate concentration. There was an increase of the CS lactate concentration
      during aortic cross-clamp period in both groups. After release of the aortic
      cross-clamp, there was an increase of the CS lactate concentration in the
      antegrade group, and a decrease of CS lactate in the retrograde group. Analysis
      of the patients operated with antegrade delivery of cardioplegia showed an
      increase of the CS lactate concentration in 9/10 patients after aortic cross
      clamp release. In the retrograde group, in 8/11 patients the CS lactate
      concentration decreased immediately after aortic cross-clamp release. Whereas the
      differences in the CS lactate concentration were not significantly different, the
      lactate extaction immediately after aortic cross-clamp release was significantly
      higher for the retrograde group (p = 0.034). This can be related to a faster
      reconsolidation of mitochondrial oxidative phosphorylation in the retrograde
      group. For the other registered parameters, hemodynamic recovery of cardiac
      function, release of creatine kinase MB isoenzyme, and clinical outcome, there
      was no significant difference between the groups. Based on this study we conclude
      that retrograde delivery of a cold non-oxygenated cardioplegic solution results
      in a better preservation of myocardial energy reserve than antegrade delivery.

PMID- 7502282
TI  - Atrial fibrillation after blood and crystalloid cardioplegia in CABG patients.
AB  - In an investigation of factors influencing the occurrence of supraventricular
      arrhythmias, ninety-eight patients were randomized to receive either cold blood
      (n = 49) or cold crystalloid (n = 49) cardioplegia during an elective coronary
      artery bypass grafting operation and were followed for seven days for the
      development of postoperative atrial fibrillation (AF). Twenty-one patients in the
      blood-cardioplegia group and nine in the crystalloid-cardioplegia group developed
      AF (p < 0.01). The patients who developed AF had smaller CK-MB enzyme leaks one
      hour after the operation (57 +/- 26 iu/L for AF vs 70 +/- 30 iu/L for normal
      rhythm, p < 0.05), and more often spontaneous beating after cross-clamp release
      (37% vs 15%, p < 0.05), which indicates that AF was not associated with poor
      ventricular myocardial protection or conduction system protection. The lesser
      amount of cardioprotective solution with AF patients (3551 +/- 1585 ml vs 4064 +/
      1562 ml, p < 0.05) and the time of onset of atrial fibrillation (4.0 +/- 1.8
      postop. days) indicate that AF is probably caused at least partly by a
      reperfusion injury at the atrial level. The possibility of atrial fibrillation
      can be reduced by giving sufficient cardioplegia and giving beta-blocking
      medicine after the operation.

PMID- 7502283
TI  - Modified trap-door thoracotomy for malignancies invading the subclavian and
      innominate vessels.
AB  - Thirteen patients with malignancies which had invaded the subclavian vessels
      and/or distal border of the innominate vessels were operated on through modified
      "trap-door" thoracotomy. The modification is the additional resection of the
      first rib from inside the thorax. Tumors consisted of thyroid cancer in 5
      patients, thymic tumor in 3, Pancoast tumor in 3, and lymphoma in 2. Invaded
      vessels were on the left side in 9 cases, on the right in 3, and bilateral in
      one. Subclavian and/or innominate veins were resected in 12 cases and
      reconstructed in 5. The remaining case was treated with resection of the right
      innominate and subclavian artery and its vascular reconstruction. Compared to
      original trap-door thoracotomy, the modification provided a more adequate opening
      in the chest wall and more extensive exposure of the entire subclavian vessels,
      which made distal vascular control safe and easy. Postoperative complications
      occurred in one patient, who suffered chylothorax. In conclusion, modified trap
      door thoracotomy is a viable and useful approach in the resection of malignancies
      which have invaded the subclavian and/or distal border of the innominate vessels.

PMID- 7502284
TI  - Transfemoral intraluminal stent graft implanted for thoracic aortic aneurysm.
AB  - We describe two patients with inoperable descending thoracic aortic aneurysm. The
      first patient had complained of severe back pain for at least thirteen years.
      Radiological examination revealed a large posterior mediastinal mass that was
      misdiagnosed in 1981. Follow-up studies in 1992 revealed this mass to be a large
      descending thoracic aortic aneurysm, eroding the vertebral bodies of T3 through
      T6 and entering the spinal canal. Because of the high risk, thoracic aortic
      surgery was not performed. The second patient had an acute descending thoracic
      aortic aneurysm. There was contraindication to a second surgical approach due to
      previous thoracotomy. Both patients underwent an intraluminal bypass of the
      descending thoracic aorta with a stent graft. Postplacement aortogram and follow
      up studies showed that aneurysm was effectively excluded. We believe that this
      type of therapy should be offered to selected individuals who are considered by
      cardiovascular surgeons to be a high risk for thoracic aneurysm surgery.

PMID- 7502285
TI  - Aortic bioprosthesis without early anticoagulation--risk of thromboembolism.
AB  - Anticoagulation after implantation of a bioprosthetic heart valve has been
      suggested during a high-risk period of 3 months following surgery. There is
      little information available concerning the risk of thromboembolism during this
      period if anticoagulation is not carried out. However, this is of interest since
      60-80% of all bleeding complications due to anticoagulation occur during the
      first year of treatment. Between 1983 and 1993, 57 of our patients did not
      receive oral anticoagulation after implantation of a bioprothesis in the aortic
      position (49 Hancock, 7 Mitroflow and one Edwards stentless). All patients were
      investigated retrospectively. A risk for thromboembolic complications of 1.75% is
      calculated for the first six months following surgery, being 3.5 per 100
      patients/year. There seems to be no advantage in standard anticoagulation (INR
      2.5-4) with its risk of serious bleeding complications of about 4% during this
      period of treatment. Low-dose anticoagulation (INR 2.0-2.3), however, preferably
      in combination with prothrombin estimation by the patients, seems to offer a
      relatively safe treatment for these patients.

PMID- 7502286
TI  - Direct delivery of cardioplegia to the coronary arteries during arterial switch
      operation.
AB  - A DLP pediatric cardioplegia cannula was used to deliver cardioplegic solution to
      the coronary arteries: it seals on the artery button. The technique has been used
      in consecutive 37 patients during arterial switch operation without complication.
      This way of delivering cardioplegia solution is simple and effective.

PMID- 7502287
TI  - Fatal fungal infection of an ascending aortic graft.
AB  - In a 57-year-old male with aortic valve stenosis and severe poststenotic dilation
      of the ascending aorta an aortic valve replacement and interposition of the
      dilated aortic segment with a Dacron prosthesis were carried out. Perioperative
      course was uneventful. Four months after dismission the patient presented with
      septic fever and recurrent arterial emboli. Histological evaluation of the
      thrombotic material found fungal masses of Aspergillus flavus. Although adequate
      antimycotic treatment was started immediately the patient died two days later.
      Postmortem examination revealed massive fungal infection of the Dacron prosthesis
      while the aortic allograft appeared free from infection. The symptoms of a fungal
      infection and possible diagnostic strategies are discussed.

PMID- 7502288
TI  - Correction of pectus excavatum combined with open heart surgery in a patient with
      Marfan's syndrome.
AB  - We report a patient with Marfan's syndrome and pectus excavatum who underwent
      open heart surgery with simultaneous correction of the sternal malformation.
      Permanent internal stabilization, achieved by bilateral overlapping of the
      bevelled ends of the lowest ribs and reinforced with sternal closure wires
      offered a maintained postoperative chest wall stability, avoided the potential
      postoperative complications of cardiac compression, and improved the aesthetic
      appearance of the anterior chest wall. The increased risk of bleeding due to
      extensive dissection was minimized by postponing the repair of pectus excavatum
      to when protamin is administered after termination of cardiopulmonary bypass.

PMID- 7502289
TI  - Combined membranous obstruction and saccular aneurysm of the inferior vena cava.
AB  - The authors report the history of a 35-year-old man who was operated on because
      of an asymptomatic combined membranous obstruction and saccular aneurysm of the
      inferior vena cava (IVC) at diaphragmatic level. Using extracorporeal circulation
      as well as hypothermia, aneurysm and IVC obstruction were resected and the IVC
      reconstructed using pericardium. This case and the experience reported in the
      literature is discussed.

PMID- 7502290
TI  - Acute Budd-Chiari syndrome due to inferior vena cava occlusion following blunt
      trauma.
AB  - Inferior vena cava (IVC) thrombosis or obstruction is a complication rarely
      associated with blunt trauma. We present a case of IVC thrombo-occlusive lesion
      with both hepatic and renal failure which developed after a thoracoabdominal
      blunt trauma. Direct thrombectomy and patch cavoplasty were successfully carried
      out under deep hypothermia using cardiopulmonary bypass.

PMID- 7502291
TI  - Surgical treatment of splanchnic artery aneurysms secondary to medial
      degeneration: report of two cases.
AB  - Although splanchnic artery aneurysms are an uncommon form of vascular disease,
      splenic artery aneurysms are the third most common intraabdominal aneurysms,
      followed by aneurysms of the infrarenal aorta and iliac arteries. In this report,
      we present two splanchnic artery aneurysms, one symptomatic located in the
      superior mesenteric artery and one found incidentally in the splenic artery. In
      the first case reconstructive surgery was carried out. In the second patient the
      splenic artery aneurysm was excised and splenectomy was performed. The incidence,
      clinical presentation, pathophysiology, evaluation, and treatment modalities are
      discussed.

PMID- 7502292
TI  - Postural palpitations--a curious presentation of intrathoracic phaeochromocytoma.

PMID- 7502293
TI  - The sternocleidomastoid flap for treatment of a septic sternum defect.
AB  - After sternotomy for prosthetic repair of the ascending aorta and replacement of
      the aortic valve with a bioprosthesis in a 70-year-old woman local wound
      infection developed. Preliminary conservative treatment did not succeed. Because
      of the high risk for the patient due to local infection and partial exposure of
      the aortic prosthesis there was an indication for local flap surgery. Both
      healing of the infection and covering the prosthesis was achieved using a
      sternocleidomastoideus muscle flap.

PMID- 7502294
TI  - Successful surgery after complete disruption of the right bronchial system.
AB  - A case of successful surgical repair of a complex rupture of the right bronchial
      system in a twenty-nine-year-old man is presented. Complete primary bronchial
      reconstruction and intensive postoperative care was required to provide bronchial
      continuity and to avoid major pulmonary resection. Problems concerning diagnosis,
      surgical technique, and postoperative management are discussed. The good
      postoperative outcome may encourage bronchial repair instead of resection in
      complex bronchial disruptions.

PMID- 7502295
TI  - [The immunoadjuvant properties of hydroxyapatite with ultrahigh dispersity].
AB  - Chemically pure hydroxyapatite (HA) with particles less than 140 microns, less
      than 60 microns, and 0.01 to 0.03 microns was studied. The immunoadjuvant
      properties were assessed from the count of IgM-secreting cells and titer of IgG
      antibodies. Mice were immunized with Salmonella Vi antigen, using mixtures of the
      antigen with HA with different size of particles. Preparations with particles
      less than 60 microns and 0.01 to 0.03 micron had a reliable immunoadjuvant
      effect, whereas HA with particles of up to 140 microns in size did not show such
      an effect; these data are in line with those published elsewhere about HA as a
      surfactant. At the same time, our findings give grounds to speak about new
      prospects of HA use as a carrier of immunocorrective properties.

PMID- 7502296
TI  - [Estrogen receptors in the tissues of the marginal periodontium of patients with
      chronic generalized periodontitis].
AB  - Biopsy of the periodontal tissues was carried out in 29 patients with chronic
      generalized periodontitis in order to detect sex steroid receptors. Estrogen
      receptors in different levels were found in 58.6% of biopsy specimens. This
      implies that the trophic effect of sex steroids on the periodontium should not be
      ruled out.

PMID- 7502297
TI  - [The use of dalargin for treating recurrent aphthous stomatitis].

PMID- 7502298
TI  - [The lysosomal hydrolase activity in the blood of patients with inflammatory
      processes in the parotid gland with surgical pathology of the organs of the
      abdominal cavity].
AB  - Activities of lysosomal enzymes (acid phosphatase, beta-galactosidase, cathepsin
      D) were measured in the blood of 38 patients with acute nonepidemic parotitis,
      caused by surgical diseases of the abdominal organs, and the status of glutathion
      antioxidant system studied. When appearing in the blood, lysosomal enzymes were
      found to join the chain cytolytic process or local proteolysis reactions, thus
      possibly becoming an important pathogenetic component in the development of acute
      parotitis induced by surgical diseases of the abdominal organs. The authors come
      to a conclusion about contribution of lysosomal enzymes to the mechanisms of
      impairment of the parotid gland, an increased level of these enzymes in the blood
      being indicative of pathologic changes on tissues. The authors emphasize that
      current approaches to pathogenetic treatment of acute nonepidemic parotitis
      should be revised.

PMID- 7502299
TI  - [Reparative osteogenesis during the treatment of mandibular fractures under
      different medical geographic conditions].
AB  - A comparative analysis of the course of repair osteogenesis in patients with
      mandibular fractures living in the Amur and Ivano-Frankovsk regions was carried
      out. Protein and mineral metabolism, hemogram patterns, types and incidence of
      complications were under study. Indexes based on the "desirability function" were
      used to assess the metabolic, repair, and inflammatory processes. Unfavorable
      effects of the hypo- and uncomfortable environmental conditions on the course of
      regeneration after mandibular fractures were revealed and a conclusion made about
      the necessity of a differentiated approach to the treatment of patients with
      mandibular fractures living under different climatic and geographic conditions.

PMID- 7502300
TI  - [The use of hydroxyapatite with ultrahigh dispersity in the combined treatment of
      patients with mandibular fractures].
AB  - Altogether 125 patients with mandibular fractures of different localization were
      treated. Implantation of ultrahigh dispersed hydroxyapatite was included in the
      treatment schemes, both surgical and conservative, of 65 of these patients. Such
      implantations were found easy to perform, well tolerated by the patients, and
      causing no side effects. The incidence of complications in this group was by
      6.78% lower than in controls treated by the traditional methods alone and by
      7.16% lower than in all patients with mandibular fractures treated over a year.
      The mean disability period was reduced by 4.8 days when this preparation was
      used.

PMID- 7502301
TI  - [The radiation therapy of skin cancer of the face].
AB  - Results of three-year radiotherapy are assessed in 586 patients with skin cancer,
      with tumors localized on the skin of the face in 484 of these. The results of
      treatment were found to depend on the histological structure of the tumor and
      disease stage: 100% cure was attained in patients with basal-cell carcinomas and
      T1 stage, whereas only 7% of patients with T4 stage were cured; in patients with
      squamous-cell carcinoma these figures were, respectively, 96.2 and 10%.

PMID- 7502302
TI  - [The concept of the pathogenesis of occlusive disorders in diseases of the
      temporomandibular joint].
AB  - Abnormal occlusion developing in adult patients is always caused by involvement
      of the temporomandibular joints. Destructive diseases of an infectious origin are
      characterized by unilateral involvement of the joints, unilateral reduction of
      the interocclusal height, and increased abrasion of teeth due to increased
      masticatory loading. Occlusive contact is preserved in all teeth. The second
      group of destructive diseases of the temporomandibular joint includes rheumatoid
      arthritis and systemic scleroderma and is characterized by symmetrical
      involvement, polyarthritis, and rapid progress. Clinically frontal occlusion
      develops, which is caused by deformation of articular processes, mandibular body,
      angle, and branch.

PMID- 7502303
TI  - [The potentials of nerve neurotization in the treatment of patients with facial
      paralysis].
AB  - Variants of nerve neurotization are described. Indications for their use are
      defined and potentialities of nerve neurotization assessed. Clinical results
      demonstrate its efficacy both in cases with facial paralysis and with partial
      ptosis of the upper eyelids or paralysis of the tongue.

PMID- 7502304
TI  - [The thoracodorsal flap in facial reconstruction].
AB  - Seventy autotransplantations of thoracodorsal flaps were carried out to repair
      defects on the head, face, and neck. Variants of such flaps are described. An
      extensive defect of any localization is an indication for the use of such grafts.

PMID- 7502306
TI  - [Plasma technology in orthodontic practice. 2].

PMID- 7502305
TI  - [The removal of folds and wrinkles in the glabella area].
AB  - Analysis of late results of operations performed in 160 patients to remove
      excessive skin and wrinkles on the forehead showed that good results were
      attained in only 40% cases. This was because surgical interventions to remove
      skin excess on the forehead and to repair the eyebrows in ptosis did not include
      resection of the muscles which created folds in the glabella. Resection of the
      muscles moving the eyebrows together helped appreciably improve the remote
      results of surgery.

PMID- 7502307
TI  - [The certification of specialists (the order of the Ministry of Health and the
      Medical Industry of the Russian Federation and a commentary)].

PMID- 7502308
TI  - [The parameters of molding stock after disinfection by dynamic plasma
      processing].

PMID- 7502309
TI  - [The function of the maxillofacial muscles in dentition defects and periodontal
      diseases].
AB  - Quantitative and qualitative changes of the function of the jaws in dentition
      defects and periodontal diseases were assessed. Besides dysfunction of every
      muscle involved, disordered relationships between antagonist and synergic muscles
      were revealed. Coordinated activity of maxillofacial muscles was 56.4% disordered
      in class I defects of dentition, 70.5% impaired in class II defects, and 83.3%
      disordered in class III defects.

PMID- 7502310
TI  - [The clinical manifestations of herpetic stomatitis in children with acute
      lymphoblastic leukemia].
AB  - Clinical (n = 137) and virological (n = 50) analysis of the course of herpetic
      stomatitis in children with acute lymphoblastic leukemia was carried out. 97.8 +/
      1.4% of cases were relapses of a chronic herpetic infection, 73.8 +/- 3.7% of
      cases ran a medium severe or severe course. Herpetic stomatitis in children
      suffering from acute lymphoblastic leukemia was characterized by the following
      features: 1) a high risk of infection generalization; 2) progressive necrosis of
      tissues in a state of leukopenia; 3) infiltration at the site of necrosis; 4)
      tissue anemia; and 5) risk of hemorrhage from necrotic sites.

PMID- 7502311
TI  - [The x-ray changes in the facial skull in children and adolescents with bite
      anomalies].
AB  - Analysis of x-ray parameters of the facial skull in 102 children and adolescents
      directed for orthodontic treatment because of occlusion abnormalities showed that
      the changes in the dentition ratio are caused by disorders in the growth and
      formation of facial bones and skull base. X-ray characteristics of different
      types of such disorders are presented.

PMID- 7502312
TI  - [The indices of dental and overall status in homogeneous groups].

PMID- 7502314
TI  - [A set of instruments for laying out the angles for additional incisions in
      vestibuloplasty].

PMID- 7502313
TI  - [The demand for dental care among persons of older age groups].
AB  - The need in dental care was analyzed basing on the results of examinations of
      1806 representatives of the older age groups. Only 1.6% of the examinees,
      however, needs to consult a dentist, the mean CDR (carious, decayed, removed
      teeth) index being 15.4, with a trend to an increase with age. The proportion of
      toothless subjects is high. A high incidence of carious teeth means that elderly
      and senile subjects are in need of all types of dental care. The diagnosis and
      treatment are difficult in this patient population because of age-specific
      changes in dental tissues.

PMID- 7502316
TI  - [30 years of experience in using lasers in dentistry].

PMID- 7502315
TI  - [Physician errors in the diagnosis of so-called Kuttner's "tumor"].
AB  - A diagnostic error occurred in a case with one of the forms of chronic
      sialadenitis, the so-called Kuttner's [correction of Kuttmer's] "tumor". This
      disease resembles a tumor by its clinical course, and this may become the cause
      of an unjustified surgical intervention. The etiology of the disease is unknown;
      possible enlargement of the submandibular salivary glands as their substitute
      hypertrophy in diabetes mellitus is discussed.

PMID- 7502317
TI  - [A discussion of 2 remarkable schools].
AB  - Opinions on the role of the pulp in the status of dental enamel in health and
      caries are contradictory. Three parameters are discussed: the notion of a normal
      enamel, the initiation of a carious process, and prediction of the disease
      course. The third aspect of the discussion is touched upon in this paper:
      prediction of caries. The enamel resistance test (ERT) is suggested to be used
      for caries prediction, although its value is denied by some authors. The author
      of this paper advocates wide use of prophylactic measures, no matter what the
      results of ERT are.

PMID- 7502318
TI  - [The history of the integration of the medical sciences in the study of diseases
      of the oral mucosa].

PMID- 7502319
TI  - [The experimental treatment of chronic periodontitis using ortofen].

PMID- 7502320
TI  - Children discharged following nutritional rehabilitation: a follow-up study.
AB  - The results of a 1-year follow up of children discharged from a nutritional
      rehabilitation centre (NRC) in eastern Nepal are presented. One hundred and one
      children were visited at home on discharge from the NRC, at 6 months and 1 year
      later. Data were collected concurrently on one sibling and two neighbouring
      children matched for age and sex. Anthropometry was carried out at each visit and
      information collected on socio-economic variables and child feeding practices. A
      significantly higher death rate was observed in index children as compared with
      controls. Index children demonstrated catch-up growth with both greater weight
      gain and faster increases in height than either control group post-discharge. At
      6 months, mean weight-for-height was similar in all three groups but at one year
      mean height-for-age was still lower in the index children as compared with
      controls. The prognosis for female children appeared to be poorer than for boys.

PMID- 7502321
TI  - Acute isovolaemic haemodilution: the best option for autologous blood transfusion
      in Africa?
AB  - The purpose of this study was to identify the best method of autologous blood
      transfusion to be applied in an East African hospital. One hundred and nine
      consecutive patients for whom major blood loss was anticipated were enrolled.
      Seventeen patients donated 1 unit of blood 3 days preoperatively and 92 underwent
      acute isovolaemic haemodilution prior to induction of anaesthesia. For the
      haemodiluted patients a 2:1 ratio of sterile pryogen-free saline to collected
      blood was used. One of the 16 patients from whom 2 units were withdrawn by
      haemodilution experienced hypovolaemia which was rapidly restored by additional
      transfusion of colloid. Of the patients who donated blood preoperatively only
      23.5% were autotransfused compared to 98.9% of the haemodiluted patients. Of the
      latter 23.9% (22) had an intraoperative blood loss exceeding 15% of their total
      blood volume and 7.6% (7) lost more than 25%. Only one received homologous blood
      in addition. For hospitals with limited blood bank facilities and regular
      cancellation of surgery, the use of acute isovolaemic haemodilution is
      recommended. A 3:1 ratio of saline to blood is now advised when 1 unit is
      withdrawn and a part replacement with crystalloid when 2 units are collected.

PMID- 7502322
TI  - Haematological profile in typhoid fever.
AB  - The haematological profile in 20 culture proven patients with typhoid fever of
      varying age and of both sexes was studied. Significant changes observed were
      anaemia, leucopenia, eosinopenia, thrombocytopenia and sub-clinical disseminated
      intravascular coagulation. The bone marrow of typhoid patients showed myeloid
      maturation arrest, decrease in the number of erythroblasts and megakaryocytes
      with increased phagocytic activity of histiocytes.

PMID- 7502323
TI  - Shigellosis in Mozambique: the 1993 outbreak rehabilitation--a follow-up study.
AB  - In this paper we describe a dysentery outbreak in Mozambique during 1993. A total
      of 47,483 cases and 199 deaths were reported, with an incidence rate of
      292.5/100,000 and a fatality rate of 0.25% for the whole country. Of the 144
      districts in the country 123 were affected: those situated along the principal
      communications routes and corridors had high incidence rates, up to 3308/100,000.
      All the provincial capitals were affected with incidence rates between 59.6 and
      4381.8/100,000. Shigella dysenteriae type 1 was identified as the aetiological
      agent. This strain was sensitive to nalidixic acid, cephalosporins, gentamicin
      and kanamycin, and resistant to tetracyclines, trimethoprim, chloramphenicol,
      ampicillin, sulphisoxazole, cotrimoxazol and erythromycin. This is the first
      dysentery epidemic caused by S. dysenteriae type 1 reported in Mozambique. The
      epidemic still continues. Population movements after the war, poor levels of
      sanitation and poverty contributed to the gravity of the outbreak.

PMID- 7502324
TI  - Salmonella septic arthritis in Zambian children.
AB  - Thirty-four children under the age of 3 years with septic arthritis presented to
      Mukinge Hospital between 1 January 1992 and 31 March 1993. Twenty-six of these
      cultured Salmonella spp. The salmonella group comprised 17 males and 9 females
      with an average age of 10 months. Most patients were anaemic and all were under
      50th centile for weight. The commonest presentation was swelling, pyrexia and non
      use of the limb. The mean white cell count (WBC) was 14,000/mm3 and the mean
      erythrocyte sedimentation rate (ESR) was 15.8 mm/h, but in many cases both the
      WBC and ESR were normal. All patients were treated with drainage and antibiotics.
      All made a good recovery and were discharged pain free, apyrexial and using the
      affected joint. One patient was readmitted because of recurrent infection. Nine
      patients reviewed after 1 month had continued good function. We consider that
      malnutrition and local trauma are predisposing factors to the development of
      salmonella septic arthritis in a population where salmonella is endemic.

PMID- 7502325
TI  - Are our information, education and communication-based interventions too
      superficial?

PMID- 7502326
TI  - Changing patterns of medical disease in Soweto, South Africa 1981-1990.

PMID- 7502327
TI  - Alternative external fixation for open fractures of the lower leg.
AB  - A locally made cheap external skeletal fixator using wood and its use in seven
      patients with an open fracture of the lower leg together with soft-tissue injury
      are described. The application of the external fixator in such fractures is a
      good example of appropriate technology and facilitates the daily hygienic nursing
      care of wounds.

PMID- 7502328
TI  - Cholera: water pasteurization using solar energy.

PMID- 7502329
TI  - Dapsone syndrome.

PMID- 7502330
TI  - The role of doctors in influencing infant feeding practices in South India.
AB  - Infant feeding practices are influenced by many factors including culture,
      household income, literacy, advice from health care workers and advertising. In
      South India doctors play a very significant role in influencing a mother's
      decision about when or whether to supplement breastfeeding with formula feeds.
      Doctors exert their influence on mothers both directly and indirectly, and they
      are increasingly targeted by commercial infant food companies. Doctors need
      continuing education about nutrition education, lactation management, and a
      greater awareness about the influence of inappropriate promotional practices by
      companies.

PMID- 7502331
TI  - Blindness in leprosy patients of Kaduna State, Northern Nigeria.
AB  - We examined the eyes of 311 leprosy patients to determine the prevalence of
      blindness and impaired vision, and the causes of blindness in leprosy patients in
      Northern Nigeria. There was impaired vision or blindness in 74 eyes. Both eyes
      were affected in 5.1% of patients while 2.9% were totally blind. Leprosy alone
      was responsible for total blindness in 1.3% of patients, while other ocular
      diseases contributed to blindness in 1.6%. Exposure keratitis (21.3%), corneal
      opacities (13.5%) and chronic uveitis (10.1%) were the commonest leprotic cause
      of blindness. Primary care and early intervention could help prevent blindness in
      many of these patients. Primary eye care should therefore be given a prominent
      position in the training of carers of leprosy patients.

PMID- 7502332
TI  - Fatal pulmonary aspiration of barium during oesophagography.

PMID- 7502333
TI  - A case of haemochromatosis in Zambia.

PMID- 7502334
TI  - Acute retention of urine due to prostatic a abscess.

PMID- 7502335
TI  - Accidental ingestion of vitamin A.

PMID- 7502336
TI  - Does antimony therapy cause bleeding in kala-azar patients and why?

PMID- 7502337
TI  - The value of a prospective report on maternal deaths: a Trinidad experience.

PMID- 7502338
TI  - Pitfalls in the diagnosis of jaundiced patients in the tropics.

PMID- 7502339
TI  - Fire hazard of a dug-well latrine.

PMID- 7502340
TI  - Need for uniform display of expiry date on medicine samples.

PMID- 7502341
TI  - Acute intoxication from newly-introduced cassava during drought in Mozambique.

PMID- 7502342
TI  - How effective is community health education in preventing worm infestation?

PMID- 7502344
TI  - East Coast fever as a continued constraint to livestock improvement in Tanzania:
      a case study.
AB  - An investigation was carried out into the cause of deaths in a recently
      established dairy farm with 211 animals. Clinical examination revealed that 14
      out of 15 sick animals were depressed, pyrexic, anorexic and had variable degrees
      of respiratory distress and enlarged lymph nodes. These clinical signs were
      suggestive of East Coast fever (ECF). This was confirmed on positive
      demonstration of piroplasms and macroschizonts in blood and lymph node smears
      respectively, and on post-mortem examination. Parasites were also demonstrated in
      smears taken from 5 other animals which were pyrexic and had enlarged lymph
      nodes. Epidemiological investigation revealed that the occurrence of the disease
      was associated with contact with tick-infested pastures and unsatisfactory tick
      control due to improper dipping of the herd. The use of pasture by pastoral
      cattle which are rarely dipped also increased tick infestation. It is concluded
      that, unless effective disease control is applied ECF will continue to be a major
      killer disease of cattle in Tanzania.

PMID- 7502343
TI  - Effects of tick infestation and tick-borne disease infections (heartwater,
      anaplasmosis and babesiosis) on the lactation and weight gain of Mashona cattle
      in south-eastern Zimbabwe.
AB  - The effects of ticks and tick-borne disease infections on the lactation and
      weight gain of Mashona cattle were studied at Mbizi Quarantine Station in the
      south-eastern lowveld of Zimbabwe. Twenty-nine Mashona cows were allocated to 2
      balanced groups and kept in separate paddocks at a stocking rate of one animal
      per 8 ha. One group received regular acaricide treatment to control bont
      (Amblyomma hebraeum) and other ticks. The other group was left untreated. The
      cows were artificially inseminated. The acaricide-treated cows and calves were
      essentially tick free throughout the experiment, while the untreated cows and
      calves were continuously tick infested. There was a drought-related decline in
      tick infestations in the second year of the experiment. Antibodies to Cowdria
      ruminantium, Babesia bigemina and Anaplasma marginale were detected in cows and
      calves from both groups, though the untreated group had significantly higher
      titres to C. ruminantium (P < 0.001). The total, measured amount of milk suckled
      by untreated calves was significantly more than treated calves (273 kg vs. 241
      kg, P < or = 0.05). By interpolating between the twice weekly measurements, it
      was calculated that over the entire lactation untreated calves suckled an average
      of 935 kg/hd vs. 837 kg/hd for the treated group. There were no statistical
      differences in the weights of the 2 groups of calves at birth, weaning, 180 and
      210 days post partum (P < 0.05). For cows, there were no statistically
      significant differences in gestation periods (288 vs. 279 days), reconception
      rates or weight patterns over time (P < 0.05). The results show that intensive
      acaricide treatment in areas of Zimbabwe where heartwater is enzootically stable
      is uneconomical. The maintenance of enzootic stability for tick-borne diseases
      through minimal tick control is clearly a more economic and practical control
      option.

PMID- 7502345
TI  - Comparison of characteristics of life cycle in female ticks collected on N'Dama
      and zebu cattle.
AB  - Characteristics of the life cycle of female ticks (Amblyomma variegatum, Hyalomma
      truncatum and Boophilus geigyi) fed on N'Dama and zebu cattle were studied in the
      laboratory from pre-oviposition period to larval development. Percentage of A.
      variegatum eggs hatched and engorgement weight of H. truncatum were lower in
      ticks collected on N'Dama than on zebu cattle. Laboratory results confirmed field
      observations of species specific tick resistance in the N'Dama breed.

PMID- 7502346
TI  - Epidemiology and control of rabies in Malawi.
AB  - The official statistics for rabies in animals and man are reviewed and
      inaccuracies discussed. Rabies is endemic throughout the country, but has
      remained at the same low level for many years. An average of 186 cases are
      confirmed in animals each year. Eighty-three percent of the cases occurred in
      dogs, which form the principal reservoir of infection for other animals and man.
      Jackals and hyenas accounted for 5% of the cases. Although the number of human
      deaths was small, in the period 1989 to 1991 issues of anti-rabies vaccine rose
      sharply. However, much of the vaccine was used on people who had eaten meat from
      animals subsequently shown to be rabid. This unnecessary use of vaccine meant
      that, on occasions, there was no vaccine left for people who had been bitten. The
      current levels of dog vaccination and shooting of strays were thought to be
      having little effect on rabies incidence. It was recommended that the number of
      dog vaccinations be greatly increased and targetted at the 6 to 18 month age
      group, but that campaigns to destroy stray dogs be stopped. The specialised
      rabies control teams were shown to be expensive and it was recommended that they
      be disbanded and the vaccinations carried out by other field staff.

PMID- 7502347
TI  - Rabies in the State of Morelos, Mexico.
AB  - Rabies incidence is high in the State of Morelos, Mexico. The present study is
      based on the data obtained from relevant Government institutions. The results
      from 1980 to 1990 show an average of 3.3 human, and from 1985 to 1990 a total of
      3,173 animal rabies positive reports. It was concluded that the anti-rabies
      programme in Mexico, particularly in the State of Morelos, has not produced
      adequate results.

PMID- 7502348
TI  - Occurrence of haemagglutination-inhibition antibodies against egg drop syndrome
      1976 virus in broilers.
AB  - From a total of 22 broiler flocks 347 serum samples were screened by the
      haemagglutination inhibition (HI) test and 114 (32.9%) were positive for
      antibodies to egg drop syndrome 1976 (EDS'76). The HI titres of the serum samples
      ranged from 2 to 9 log2 and the overall geometric mean titre was 3.9 log2. Of the
      serum samples 82.5% showed HI titres between 2(2) to 2(5) and the most frequent
      titre was 2(3). All the flocks were positive and the flock prevalence of HI
      antibodies ranged from 13.3 to 46.6 per cent. The age distribution of HI
      antibodies and their titres have also been recorded. The widespread prevalence of
      EDS'76 virus infection in broilers and its likely significance are discussed.

PMID- 7502349
TI  - Suitable samples from remote areas for Newcastle disease diagnosis.

PMID- 7502350
TI  - Field outbreak of infectious stunting syndrome in broiler chickens in Jordan.

PMID- 7502351
TI  - Influence of season and housing on ovarian activity of indigenous goats in
      Zimbabwe.
AB  - Progesterone profiles were monitored in goats housed in single (n = 9) or group
      (n = 14) pens during winter (JJA) and spring (SON). Normal cycles (n = 97) were <
      or = 30 days. Extended cycles (n = 45) were > 30 days and, except for one cycle
      with a persistent corpus luteum, had periovulatory periods of 10 to 20 days (n =
      29) or averaging 65.1 days in length (n = 15), mostly characterised by recurrent
      oestrus and/or occasional transient rises in progesterone. The proportion of
      normal cycles occurring in winter was 87.5% (28/32) and 77.7% (42/54) for goats
      in single and group pens respectively, falling to 62.5% (15/24) and 37.5% (12/32)
      respectively in spring. The distribution of normal vs extended cycles according
      to season was significant (P < 0.05, single; P < 0.001 group pens). Goats housed
      communally experienced a greater fall in the percentage of normal cycles in
      spring, possibly due to increased stress associated with group feeding. Within
      each season, however, housing per se did not influence the distribution of normal
      vs extended cycles. For normal cycles, Harvey's Analysis of Variance showed that
      season was significantly associated with length of the periovulatory period (3.99
      days (JJA) vs 5.79 days (SON); P < 0.001), oestrus detection rate (87% (JJA) vs
      55% (SON); P < 0.01) and oestrus duration (1.94 days (JJA) vs 1.13 days (SON); P
      < 0.05). In contrast, luteal phase length was not affected by season, but was
      significantly associated with housing (16.93 days (single pens) vs 18.32 days
      (group pens); P < 0.01). The reduction in ovarian activity observed in spring may
      reflect a seasonal reduction in fertility, possibly linked with increasing
      temperature and photoperiod.

PMID- 7502352
TI  - Administration of fenbendazole in urea molasses block to dairy buffaloes in
      India.
AB  - A trial was conducted in a semi-organised buffalo farm in western India with
      strategic long-term low-level administration of fenbendazole incorporated
      medicated urea molasses blocks to understand its nematocidal efficacy and
      production response in buffaloes. Results indicated that the anthelmintic
      delivery system could effectively remove already established adult parasites and
      prevent larval establishment. The treated buffaloes produced more milk (P < 0.01)
      from 45 days onward with a net gain of 1.20 litre per day.

PMID- 7502353
TI  - Influence of suckling on calving interval of N'Dama cows in The Gambia.

PMID- 7502354
TI  - Vitamin A status of healthy infants in Ankara, Turkey.
AB  - Vitamin A deficiency is considered widespread health problem among children in
      developing countries. There are a limited number of studies related to the
      vitamin A status of children in Turkey. We studied serum vitamin A levels in 80
      healthy children less than 2 years of age admitted to Dr. Sami Ulus Children's
      Hospital for measles immunization. Vitamin A levels were determined by high
      performance liquid chromatography, and ranged from 8.5 to 34 micrograms/dl (mean
      23.54 +/- 6.86 micrograms/dl). We have shown that subclinical vitamin A
      deficiency is an important public health problem in Ankara, as approximately 30
      percent of the children examined were found to have low levels of serum vitamin A
      (< 20 micrograms/dl).

PMID- 7502355
TI  - Vitamin A levels of children with measles in Ankara, Turkey.
AB  - Recent studies show that vitamin A levels decrease during measles and that
      vitamin A therapy can improve measles outcome in children in the developing
      world. Vitamin A levels of children with measles have not been studied before in
      Turkey. Therefore we measured serum vitamin A levels in 21 children with measles
      and compared the results with "sick" and "healthy" control groups. The mean
      vitamin A levels in children with measles were markedly lower than in the "sick"
      and "healthy" control groups (p: 0.001). Vitamin A levels in children with
      measles ranged from 1.3 to 32 micrograms/dl; 11 (52%) were vitamin A deficient (<
      10 micrograms/dl). This frequency among Turkish children supports evaluation of
      vitamin A status as a part of acute management of measles in Turkey. Clinicians
      may wish to consider vitamin A therapy for children with measles according to WHO
      recommendations.

PMID- 7502356
TI  - Causes of fetal and neonatal death.
AB  - Autopsy was performed on 601 out of 654 (91.9%) fetus and newborn cases of death
      which occurred during a four-year period between 1988-1991 at Istanbul University
      Cerrahpasa Faculty of Medicine, Gynecology Department and Neonatal Unit.
      According to autopsy findings, among the main causes of death in newborns were
      infection, hyaline membrane disease, congenital anomalies, perinatal hypoxia and
      immaturity, and in the fetal period, perinatal hypoxia, asphyxia and congenital
      anomalies. In these cases, when pathologic and clinical findings were examined,
      it was observed that in 204 out of 301 newborn cases (67.8%) the clinical
      findings were well correlated with the autopsy findings; in 97 (32.2%) of the
      remaining cases the main disease and primary causes of death could not be
      determined through clinical findings; in 69 (23%) cases, in addition to the
      clinical diagnosis on autopsy, minor defects were determined on autopsy which
      were not directly related to death. When clinical and autopsy findings were
      compared, diagnoses with the highest discordance were pulmonary hemorrhage
      infection and intracranial hemorrhage.

PMID- 7502357
TI  - Analysis of patients admitted to the emergency unit of a university children's
      hospital in Turkey.
AB  - A retrospective analysis of the computerized data of patients admitted to our
      Emergency Unit Inpatient Service in 1991 was conducted to obtain data about age,
      sex, referred sources, admission period, monthly admission rates, diagnoses and
      eventual outcome. More than 47% of patients were younger than one year of age.
      The most common causes for hospital admission were infectious, respiratory and
      neurological diseases. The mean hospitalization period was 3.26 days. More than
      60% of patients were treated by the Emergency Unit staff. The net mortality rate
      was 2.9%, infectious diseases being the most common cause of mortality. We
      conclude that demographic and diagnostic data regarding admissions to the
      Emergency Unit can be utilized to develop new strategies for patient care and to
      reorganize education programs for pediatric residents.

PMID- 7502358
TI  - Serum and urine total, free and acylcarnitine levels related to age: assessment
      of renal handling of carnitine.
AB  - Control ranges of free, total and esterified carnitine in serum and spot urine
      samples of a healthy population of children and adults were established by radio
      enzymatic assay. Children were divided into three groups according to age: six
      months to two years (n = 15), three to five years (n = 19), and six to ten years
      (n = 16). The adult group ranged in age from 20 to 35 years (n = 18). Serum free
      and total carnitine displayed a significant increase up to ten years of age,
      while acylcarnitines and the acylcarnitine/free carnitine ratio decreased until
      five years of age. Urinary free carnitine increased significantly up to five
      years of age. The overall increase in urinary total carnitine was insignificant.
      Urinary acylcarnitines and the acylcarnitine/free carnitine ratio decreased
      significantly in the three- to five-years age-group, increased significantly in
      the six- to ten-years age-group and remained constant afterwards. Renal handling
      of carnitine was assessed by evaluation of the renal reabsorption rate for free
      carnitine (RRFC) and the acylcarnitine/free carnitine clearance ratio (RAFCC),
      both of which were found to increase significantly up to five years of age. These
      data suggest that a balance in carnitine metabolism and excretion seems to be
      reached only after five years of age. The establishment of reference ranges in
      different population groups is critical for the investigation of children
      suspected to suffer from inherited metabolic disorders.

PMID- 7502359
TI  - Follow-up results of synthetic vascular grafts in children undergoing
      hemodialysis.
AB  - Polytetrafluoroethylene (PTFE) grafts were inserted in the thigh of 14 children
      (7 boys and 7 girls, age 12 +/- 1.8 years) who were undergoing chronic
      hemodialysis for endstage renal disease. Removal of grafts was necessary in three
      patients within three months of implantation. In a fourth case it was indicated
      in the fifteenth month. In two cases thrombectomy was necessary. Echocardiography
      was performed in 10 patients before and three and 12 months after surgery.
      Cardiac performance followed by echocardiography did not change after one year.
      After two years the survival of grafts was 71%. It appears that synthetic grafts
      offer advantages for pediatric hemodialysis patients with arteriovenous fistula
      failure. On the other hand, this technique entails serious risks.

PMID- 7502360
TI  - Prognostic factors in Salmonella typhimurium septicemia. A 10-year retrospective
      study.
AB  - In this study, 74 S.typhimurium septicemia cases were evaluated retrospectively
      from their records, and the age and sex distribution, presence of underlying
      disease, signs and symptoms, complete blood count, liver function tests and case
      fatality rate were documented and prognostic factors determined. It has been
      shown that S.typhimurium is the most common strain causing Salmonella septicemia,
      which is more fatal in the newborn period and in the presence of an associated
      disease, while hemoglobin and leukocyte counts do not play an important role in
      the prognosis. In Salmonella septicemia, congenital heart disease was the second
      most common associated disease, which may be attributed to probable underlying
      immunodeficiency.

PMID- 7502361
TI  - Various clinical aspects of DIDMOAD (Wolfram) syndrome.
AB  - The association of juvenile diabetes mellitus (DM), diabetes insipidus (DI),
      optic atrophy (OA) and sensorineural deafness (D) is known as DIDMOAD or Wolfram
      syndrome. Aside from these four cardinal features, a wide variety of
      abnormalities of the nervous system, urinary tract and endocrine glands have been
      described in this syndrome. In this report, the clinical features of six patients
      with DIDMOAD syndrome are presented. All six patients had DM. Five of the six
      patients had DI, five OA and five displayed abnormal audiogram findings. In
      addition, two had goiter, two delayed puberty, one seizure and one mental
      retardation with depression attacks. Urinary tract dilatation was recorded in
      five patients. Four patients developed typical complications of DM. One of them
      had overt nephropathy and arthropathy despite the short duration of DM. In
      addition, this patient had diabetic retinopathy, which is considered to be rare
      in this syndrome.

PMID- 7502362
TI  - Congenital generalized lipodystrophy: Berardinelli syndrome. Report of two
      siblings.
AB  - Two successively born infants with Berardinelli syndrome, an unusual
      lipodystrophic disease, are reported. In addition to hepatomegaly, accelerated
      growth, muscle hypertrophy, lack of adipose tissue, hirsutism and
      hypertriglyceridemia, which are the characteristics of the syndrome, these
      brothers demonstrated bilateral, symmetrical, renal medullary hyperechogenicity,
      which has not before been reported in association with generalized lipodystrophy.
      Although more than 25 cases have been recorded, the metabolic defect responsible
      for this inborn error of metabolism has not yet been determined.

PMID- 7502363
TI  - Amphotericin B in the treatment of candida meningitis in three neonates.
AB  - Candidiasis is an opportunistic infection and may result in significant morbidity
      and mortality in neonates. Cerebral candidiasis is rare and usually associated
      with systemic candidiasis. Information concerning the toxicity and efficacy of
      antifungal therapy for neonates is limited. In this report, we present three
      neonates with candidiasis. All of the patients were premature with low birth
      weights, and received antibiotic therapy for one to four weeks before the onset
      of candidiasis. Candida albicans was isolated from cerebrospinal fluid cultures.
      Amphotericin B was given administered at an initial dose of 0.25 mg/kg/day
      intravenously (IV) and increased to a dosage of 2 mg/kg/day, and therapy was
      continued for three to four weeks. A transient and mild elevation in hepatic
      enzyme concentration was observed in two patients, and transient thrombocytopenia
      occurred in all of them.

PMID- 7502364
TI  - Lymphangioma treatment with Nd-YAG laser.
AB  - In the oral cavity, lymphangioma is a rare, non-odontogenic, benign neoplasm
      which originates from lymph vessels. This lesion is common in the first decade of
      life and mostly occurs on the dorsal surface and lateral border of the tongue and
      rarely arises on the palate, gingiva, buccal mucosa and lips. Treatment of the
      lesion is surgical excision, however in recent years Neodymium Yitrium Aluminum
      Garnet (Nd-YAG) laser surgery has become favorable due to its many advantages.
      This case report presents the treatment of a buccal lymphangioma in a 10-year-old
      girl by Nd-YAG laser.

PMID- 7502365
TI  - Cardiac rhabdomyosarcoma diagnosed by echocardiography.
AB  - Primary, malignant, cardiac tumors are extremely rare in infants and children.
      Only a few cases of cardiac rhabdomyosarcoma have been reported in childhood.
      Echocardiography greatly increases the rate of correct diagnosis of cardiac
      tumors. There are some cases in the literature which were diagnosed by
      echocardiography and confirmed histopathologically. In this report, a 13-year-old
      girl with the clinical findings of cardiac tamponade and who was diagnosed as
      having a cardiac tumor by two-dimensional echocardiogram is presented An
      echodense, solid tumor with irregular borders extending especially toward the
      left ventricular cavity from the apex was demonstrated on echocardiography. The
      diagnosis was confirmed histopathologically on postmortem examination.

PMID- 7502366
TI  - Angiomyolipoma located in the lumbar region of a newborn.
AB  - An unusual example of angiomyolipoma, which presented as a bulging mass on the
      right lumbar region of a newborn baby, is presented. The case described is the
      first report of a newborn with an unusually located angiomyolipoma. The most
      common predilection sites are the renal parenchyma and the retroperitoneum.
      However, most of the patients described are adults, and to the best of our
      knowledge no newborn patient has previously been reported in the literature.

PMID- 7502368
TI  - Methotrexate-induced leukoencephalopathy. A case report.
AB  - A six-year-old girl with non-Hodgkin's lymphoma who was treated with both
      intravenous (IV) and intrathecal (IT) methotrexate and developed brain damage
      secondary to the cytostatic drug is described. This patient displayed
      hypertension, hypothermia/hyperthermia, lethargy, deterioration and coma as
      clinical findings, and bilateral, focal white matter hyperintensities in the
      occipital lobes were seen in her magnetic resonance imaging (MRI). Treatment
      related leukoencephalopathy is one such adverse effect of IT methotrexate
      administration on the central nervous system and usually appears in a generalized
      form.

PMID- 7502367
TI  - Kawasaki disease associated with gallbladder hydrops.
AB  - Kawasaki disease is an acute, febrile, systemic syndrome of unknown etiology
      which principally affects young children. We present a five-year-old boy, who
      developed an unusual finding, acute hydrops of the gallbladder, in addition to
      the characteristic signs and symptoms of Kawasaki disease. Clinical features of
      the disease and treatment regimens, including early administration of intravenous
      gamma globulin (IVGG), which prevents cardiac complications, are discussed.

PMID- 7502370
TI  - The role of high-dose methylprednisolone therapy in paroxysmal nocturnal
      hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder characterized
      by intermittent hemolytic anemia. High-dose methylprednisolone (HDMP) was
      administered in two patients, eight- and 16-year-old females, with PNH. This drug
      produced a dramatic improvement in the hemoglobin level, leukocyte and platelet
      counts. No side effect was observed in either patient during the treatment
      period. The patients were followed up on an outpatient basis for six and 16
      months. In conclusion, HDMP therapy for PNH appears to be more effective and safe
      than previously reported therapies.

PMID- 7502369
TI  - Secondary acute myeloblastic leukemia in a child with acute lymphoblastic
      leukemia treated with epipodophyllotoxins.
AB  - Etoposide is a semi-synthetic, topoisomerase active podophyllotoxin derivative
      which frequently causes deletions and rearrangements on chromosomes 11q23 and
      11q22. It can cause therapy-related, acute myeloblastic leukemia in patients
      receiving the drug in a schedule-dependent manner. Here we present a case with
      acute lymphoblastic leukemia who developed secondary acute myeloblastic leukemia
      28 months after the beginning of therapy which contained etoposide on an every
      other-week schedule.

PMID- 7502372
TI  - [Medical research--optimization and independent evaluation].

PMID- 7502373
TI  - [Bibliometric analysis of Danish medical research 1986-1992].
AB  - The productivity of major Danish research milieus were compared and Denmark was
      compared with Norway and Sweden. Number and proportion of articles published in
      the 200 and 500 most cited journals increased over the years (p < 0.0001). Sweden
      had approximately twice as many articles as Denmark which had twice as many as
      Norway. The universities, private companies and societies and Steno Diabetes
      Centre had relatively most publications in the best journals. Rigshospitalet and
      the hospitals in the municipalities of Copenhagen and Arhus also did better than
      other hospitals. Impact in relation to research personnel and expenses was
      highest in the municipality of Copenhagen and at Alborg Hospital. Compared with
      number of beds, the productivity was highest at Steno and Rigshospitalet. The
      productivity was similar at the three universities in relation to research
      personnel and largest in Arhus in relation to expenses. The municipality and
      county of Copenhagen, Alborg and other provincial hospitals contributed
      relatively most to clinical trials; Rigshospitalet contributed least. The
      differences in productivity were so large that better priority setting and
      evaluation of the research seem worthwhile.

PMID- 7502371
TI  - Immune thrombocytopenic purpura in a child with Hodgkin's disease.
AB  - The occurrence of immune thrombocytopenic purpura (ITP) in Hodgkin's disease is
      uncommon. This report describes a patient who developed ITP twice before
      splenectomy, and for the third time several years later, preceding an abdominal
      relapse of the disease. We suggest that patients with a history of Hodgkin's
      disease undergo diligent searches for active disease when ITP is diagnosed. ITP
      may be the only manifestation of active disease and may precede histologic
      documentation of Hodgkin's disease by months or years.

PMID- 7502374
TI  - [Transfusion-refractory thrombocytopenia during chemotherapy: pathogenesis,
      frequency and treatment].
AB  - Transfusion refractoriness to platelets is characterized by an inadequate
      increment in the posttransfusion platelet count and/or reduced haemostatic effect
      following platelet transfusion. As a consequence of more intensive bone marrow
      toxic therapeutic approaches there is an increased use of platelet transfusion,
      and the refractory state is encountered in about half of young patients treated
      for haematological malignancies. The acquired condition is mainly due to
      alloimmunization against HLA-antigen on leucocytes in the transfused platelets or
      to non-immunological factors, e.g. fever, infections, bleedings, antibodies or
      splenomegaly. Profylactic reduction of the leucocyte content by filtration of
      transfusion products diminishes the risk of alloimmunization and the refractory
      state. Treatment of the refractory state is bleeding is transfusion with HLA
      compatible platelets or large amounts of platelet concentrates. Splenectomy and
      treatment with steroids or intravenous gammaglobulin have been unsuccessful.
      Recently a new haematopoietic growth factor, thromapoietin, which regulates
      megakaryocytopoiesis has been identified. In the near future such a recombinant
      human growth factor will most likely reduce the need for platelet transfusion and
      its side effects.

PMID- 7502375
TI  - [Physical activity and bone mineral content in postmenopausal women].
AB  - A review of 18 cross-sectional and 29 prospective studies provides evidence that
      physical exercise causes an increase in bone mineral content or at least
      preserves the bone mass of both younger and older postmenopausal women. This is
      true both for women with normal and with reduced bone mineral content. Regular
      weight-bearing exercises seem to be especially effective. There are no randomized
      studies which have been able to prove that physical exercise reduces the
      incidence and prevalence of low-energy fractures, but this reduction seems
      probable.

PMID- 7502376
TI  - [Erythropoiesis in myelodysplastic syndrome detected by multiparameter flow
      cytometry].
AB  - By staining human bone marrow cells with a monoclonal antibody reacting with
      surface antigens on erythroid precursor cells (AS-E1) and with propidium iodide
      reacting with nuclear DNA, we have evaluated the proliferative activity of
      erythropoiesis in patients with myelodysplastic syndromes using flow cytometric
      analysis. Comparing 36 patients (13 RA/RAS, 13 RAEB, 10 RAEB-t) with seven normal
      controls, significant differences in both the percentage of erythroid precursor
      cells and the fraction of these cells in the S or S-G2M-phase of the DNA cell
      cycle between the four groups were found. Since neither the percentage of
      erythroid precursor cells nor their fraction in S or S-G2M phase alone was found
      to characterize their proliferative activity, we calculated the proliferative
      fractions of the erythroid cells, i.e. the number of the erythroid precursor
      cells in S or S-G2M related to all bone marrow cells in S or S-G2M phase.
      Applying these parameters, we found significantly increased proliferative
      fractions of erythroid precursor cells in the RA/RAS patients compared to the
      normal controls (p-0.03 and 0.002 respectively), as well as a highly significant
      decrease with disease progression.

PMID- 7502377
TI  - [Cancer risk after splenectomy].
AB  - Removal of the spleen may possibly affect functions of the immune system. Cancer
      risk following splenectomy was evaluated by performing a linked register study in
      Denmark from 1977-89. From the Hospital Discharge Register we identified 1103
      patients splenectomized after traumatic rupture of the spleen and 5212 patients
      splenectomized for various malignant or non-malignant disorders and both groups
      were followed for cancer occurrence in the Danish Cancer Registry. No increased
      risk for cancer was observed among patients who underwent splenectomy due to
      trauma. In contrast, there were excesses of a number of specific cancers among
      patients who underwent splenectomy for non-traumatic reasons, but to a large
      extent this could be explained by factors related to the underlying disease
      and/or treatment of the disease.

PMID- 7502378
TI  - [Pseudoaneurysm of the femoral artery treated with color Doppler ultrasonography
      guided compression].
AB  - Conventional treatment of iatrogenic pseudoaneurysms of the femoral artery after
      puncture during arteriography with or without additional balloon-angioplasty
      consists of surgical exposure and suture of the defect. The present paper
      describes colour-Doppler guided compression treatment of 10 femoral
      pseudoaneurysms. The aneurysm and its connection to the femoral artery is
      identified by ultrasound-colour-Doppler technique and using the transducer,
      pressure is applied on the aneurysm such that in- and outflow is stopped without
      disrupting the blood flow in the underlying femoral artery. In nine cases, where
      the pseudoaneurysms were less than two weeks old, treatment was successful in all
      cases. In the remaining patients, the pseudoaneurysm had developed shortly after
      arteriography and remained constant for one year. In this case, compression did
      not result in thrombosis. It is concluded that iatrogenic puncture-derived
      >>young<< pseudoaneurysms of the femoral artery should be treated by colour
      Doppler compression except in cases of a rapidly developed large haematoma and
      circulatory instability. The latter cases should be operated immediately.

PMID- 7502379
TI  - [Congenital duodenal diaphragm in an adult. A rare cause of duodenal obstruction
      after childhood].
AB  - Since 1845, a diaphragm has been known to be able to cause duodenal obstruction.
      Not until 1944 could the condition be ascertained and treated successfully. The
      condition is normally detected in childhood and is therefore rare in the adult.
      The treatment is either duodenoduodenostomy or duodenojejunostomy or excision of
      the membrane, through a duodenotomy or by means of an endoscopic laser. In this
      report, the case of a 37-year old male is described. Although the condition is
      rare, it should be kept in mind in individuals with repetitive vomiting where
      other possibilities e.g. pyloric stenosis, are ruled out.

PMID- 7502380
TI  - [Over and over again].

PMID- 7502381
TI  - [The value of adjuvant treatment of colorectal cancer should no longer be
      ignored].

PMID- 7502382
TI  - Improved methods for determination of rotational symmetries in macromolecules.
AB  - Rotational symmetries of macromolecules are most clearly perceived in the en face
      projection and may be assessed by inspection of rotational power spectra
      calculated from electron micrographs of individual particles. However, if the
      symmetry is not contrasted strongly, this procedure may be inconclusive since the
      relevant peak may not be convincingly higher than other spectral components. To
      some extent, this is a sampling problem since the number of repeating elements
      involved is usually small. We have devised more sensitive statistical tests for
      rotational symmetry that pool the information contents of entire populations of
      particles. Both tests involve combining the rotational spectra of many particles
      and comparing them with the spectra of surrounding background areas. One method
      is based on the well known t-test which estimates whether two populations differ
      at a given significance level. In the second test, the ratio between the
      intensity of each component of the rotational spectrum and the average
      corresponding intensity for background areas is calculated, and thence, the
      cumulative product of these ratios over all particles in the data set. If a
      symmetry is present, this product gradually diverges; otherwise, it converges to
      zero. As a practical trial, the tests were applied to micrographs of negatively
      stained hexons of herpes simplex virus and confirmed their 6-fold symmetry.
      Applied to negatively stained "connector" proteins of bacteriophage T7 purified
      from a plasmid expression system, both algorithms detected polymorphism with
      distinct subpopulations of both 13-fold and 12-fold connectors.

PMID- 7502383
TI  - Crystallographic extraction and averaging of data from small image areas.
AB  - The accuracy of structure factor phases determined from electron microscope
      images is determined mainly by the level of statistical significance, which is
      limited by the low level of allowed electron exposure and by the number of
      identical unit cells that can be averaged. It is shown here that Fourier
      transforms of small image fields of purple membrane (a two-dimensional crystal
      consisting of bacteriorhodopsin and endogenous lipids) can be combined to provide
      the same quality of phases as are obtained from Fourier transforms of large image
      fields of the same total area. Although Fourier transforms of such small image
      fields are statistically significant only at lower resolution, the data from many
      such image fields can be averaged at the calculated positions of high-resolution
      reciprocal lattice points to give accurate phases. More specifically, when images
      of a size that can be recorded with CCD cameras are processed individually, key
      parameters including lattice vectors, defocus, crystal and beam tilts, and common
      phase origin can be accurately determined.

PMID- 7502384
TI  - [Behavior of artificially-induced epiphyseal groove defects. 3: Transplantation
      of autologous and homologous rib cartilage in Gottingen minipigs. Findings after
      a 16 week interval].
AB  - Drillholes of 8 mm diameter were made through the epiphyseal cartilage of the
      distal femora in 20 6-week-old Gottingen minipigs. The defects were filled with
      autologous or with homologous cartilage. This was intended to prevent epi
      metaphyseal osseous bridge formation. If of appropriate size and location, the
      latter would lead to subsequent misgrowth. In group A (autologous costal
      cartilage), at all drillholes the transplanted costal cartilage can prevent
      ossification of the defect. An epiphyseal boundary lamella was formed over the
      transplant which precluded penetration of vessels into the defect. In group B
      (homologous costal cartilage), the transplanted costal cartilage showed a
      tendency to mineralization in all preparations at the 20 drillholes available.
      The cartilage was integrated into the primary cancellous bone developing within
      the defect. An epiphyseal boundary lamella had not formed in the period of the
      experiment (in contrast to autogenous transplantation). These investigations show
      that autologous costal cartilage is superior to homologous costal cartilage in
      the potential clinical application of costal cartilage transplants in the
      treatment of Brodie abscesses or post-traumatic epiphyseodeses.

PMID- 7502385
TI  - [Muscle incoordination phenomena after surgical management of proximal rupture of
      the biceps tendon].
AB  - A significant atrophy of the biceps brachii muscle without decreasing maximal
      force during flexion in the elbow joint was shown at least 1.5 years after
      surgical refixation in 6 patients with a tendon-rupture of the long head of the
      right biceps. A decreased myoelectrical activity was found in the caput longum
      region of the muscle. The decrease correlates with an increase of spectral
      myoelectrical power in the region of caput breve or brachioradialis muscle. In
      addition compensatory recruitment processes can be supposed because of changed
      spectral myoelectrical power in the low-frequency bands. Changes of the
      morphological structure of the muscle were only found in 1 patient by sonography.

PMID- 7502386
TI  - [Experiences with plate osteosynthesis in treatment of peri- and sub-prosthetic
      femoral fractures].
AB  - Plate-osteosynthesis proves to be an established procedure in our department for
      treatment of fractures of the femur in patients older than 70 years with total
      hip replacement even when loosened. It offers the advantages of comparably low
      aggressive standard operation techniques and acceptable success rates. This
      treatment allows for short preoperative period of the patients with their typical
      multimorbidity in many traumatological departments. In younger patients with
      symptomatical loosening, simultaneous exchange of the hip prosthesis should
      always be considered. Thus, individual therapy concept including the specific
      fracture type, general condition and age must be followed for each patient.

PMID- 7502387
TI  - [Complications in 283 cruciate ligament replacement operations with free patellar
      tendon transplantation. Modification by surgical technique and surgery timing].
AB  - In our retrospective study we reviewed 283 patients who were operated on between
      1984 and 1993 after an ACL-rupture. We used a free patellar tendon bone graft in
      all patients. The aim was to assess the complications such as infections,
      thrombosis, limitation of movement and graft failures. We also looked on the
      timing of operation and the technique. We saw an overall complication rate of
      21.6%. The most common complication was a restricted range of motion in 10.9%
      which required surgery. In patients treated immediately after injury (within 7
      days) we found an arthrofibrosis rate of 17.6%. In delayed surgery (more than 4
      weeks after injury) this complication was only seen in 6.1%. The rate of
      infection was 4.6%, the rate of thrombosis 1.8% and in 4,2% we had to accept an
      ongoing instability. With these findings we now evaluate the needs and the social
      environment even more closely to find the best treatment protocol for each
      individual. In conclusion we favour secondary ACL-reconstruction.

PMID- 7502388
TI  - [Is there an increased risk of infection in trauma surgery emergency admission
      for medial personnel by unknown HIV-positive patient status?].
AB  - In the trauma emergency room 212 patients were asked--according to German law-
      for a blood sample for HIV-testing. Nine (4.2%) victims rejected the test,
      another 3 (1,4%) did not meet the study criteria since they were previously known
      to be HIV-positive or suffering from AIDS disease. None of the finally tested 200
      patients was HIV-positive. On an anonymous questionnaire that was handed out
      additionally, 64% of the patients said they would accept HIV-testing without
      consent prior to operative treatment. 49% would reject HIV-testing without
      consent in non-operative treatment.

PMID- 7502389
TI  - [Expanded indications for the Herbert-screw osteosynthesis].
AB  - Since 1984 the typical headless double threaded Herbert/Whipple screw is known in
      managing scaphoid fractures and scaphoid non-unions. We resume technical,
      biomechanical and histological aspects to point out advantages and disadvantages
      of this osteosynthesis. Our case review of 39 patients illustrate the same good
      results as achieved in treating scaphoid injuries, when using the Herbert/Whipple
      screw of a larger diameter for expanded indications other than scaphoid
      fractures, such as humeral- or radial-head fractures, Jones fractures and others.

PMID- 7502391
TI  - Corridors and towers.

PMID- 7502390
TI  - [Management of isolated sternum fracture: screening for heart contusion with
      troponin T].
AB  - In all of our reported cases a seat belt injury was the reason for the sternal
      fracture. Only 4 of 27 patients of this prospective study suffered from a heart
      contusion. None of our patients showed complications. An isolated sternal
      fracture with or without heart contusion seems to be of minor clinical
      significance. Referring to our patients a screening of a heart contusion with
      CKMB/CK activity and ECG seems to be sufficient when the trauma is not older than
      12 hours. The longer persisting plasma concentrations of cardiac troponin T
      (cTnT) enables a diagnosis of a heart contusion even after a few days.

PMID- 7502392
TI  - The radiological investigation of neurosarcoidosis.

PMID- 7502393
TI  - Pneumomediastinum and subcutaneous emphysema complicating staphylococcal
      pneumonia.

PMID- 7502394
TI  - Spurious urinary calculosis in pregnancy.

PMID- 7502395
TI  - Primitive neuroectodermal kidney tumour.

PMID- 7502396
TI  - The challenge of an inner city practice.

PMID- 7502397
TI  - General practice: any port in a storm?

PMID- 7502398
TI  - Folic acid prescription in pregnancy.
AB  - We resolved to prescribe folic acid supplements for all women who attended this
      practice during the first twelve weeks of pregnancy. Six months after this
      decision a prescription was recorded in only 13% of cases: this compared with 18%
      during the two months immediately following the decision. It was resolved to
      improve this performance and observations six months later revealed a
      prescription recorded in 63% of cases. Subsequently a new form for recording an
      antenatal consultation was devised and six months after its implementation, 100%
      recording of folate prescription for appropriate cases was observed. It was
      concluded that these simple audit exercises prompted changes in practice which
      helped to improve standards of patient care.

PMID- 7502399
TI  - A survey of the use of prostitutes (commercial sex workers) by new male attenders
      at a genito urinary medicine clinic.
AB  - This study documents the use of prostitutes (commercial sex workers) by new male
      patients attending a genito urinary medicine clinic. 541 consecutive male
      patients completed an anonymous self-administered questionnaire. 48 (8.9%) gave a
      history of previous purchase of sexual services in Northern Ireland and/or
      elsewhere; 69% of these encounters occurred outside Northern Ireland. The largest
      group were single men aged 20-29 years. 87% of those who purchased services in
      Northern Ireland were asked by the prostitute to use a condom compared with 60%
      elsewhere, but there was no significant difference in actual condom use between
      both groups (66.7% vs 72.7%) Only 21% of patients who had purchased the services
      more than once used condoms consistently and 29% were willing to pay more for
      unprotected sexual intercourse. 40% attributed their attendance at this clinic
      directly or indirectly to their encounter with a prostitute. Encounters with
      prostitutes were often related to alcohol consumption, 88% sometimes or always
      purchasing these services after drinking alcohol. Despite widespread publicity at
      risk behaviour involving unprotected sexual intercourse with prostitutes is not
      uncommon. Health education should be targeted at the young single male who
      travels outside Northern Ireland.

PMID- 7502400
TI  - Peripheral nerve blocks for paediatric day-stay surgery: one year's experience in
      a district general hospital.
AB  - Two hundred children underwent day-care surgery using peripheral nerve blockade
      as an adjunct to general anaesthesia during a twelve month period. Total post
      operative analgesia was achieved in 86%, simple oral analgesia was needed in 9%
      and the remaining 5% of patients required systemic opiate administration for
      pain.

PMID- 7502401
TI  - Transplantation for chronic pulmonary disease: referral and outcome in Northern
      Ireland, 1986-1990.
AB  - Eighteen patients have been referred for lung transplantations from Northern
      Ireland in 1986-1990. Fourteen were accepted but only four achieved
      transplantation. These rates are lower than for comparable regions in the North
      of England. The lung donation rate from Northern Ireland during the same period
      was similar to that for the United Kingdom as a whole. The low referral and
      transplant rates for Northern Ireland require reassessment of the procedures
      involved.

PMID- 7502402
TI  - General practitioner and hospital letters.
AB  - Communication by letter was assessed between hospital consultants and general
      practitioners for outpatients and inpatients referred to the Ards Hospital during
      the month of January 1993. The information was assessed to be poor in several
      sections of 104 outpatient referral letters, and of 89 inpatient referral letters
      despite a high use of the standard referral letter form. Consultant physicians'
      or senior house officers' letters to general practitioners achieved higher scores
      in 72 outpatient letters, and 152 inpatient discharge summaries. The use of
      headings was approved by 80% of general practitioners and probably accounted for
      the highest scores for the headed discharge summaries. Further support and
      education in the use of headed letters is to be encouraged.

PMID- 7502403
TI  - Paediatric consultation patterns in general practice and the accident and
      emergency department.
AB  - The age, sex, source of referral and diagnosis of children brought to a
      paediatric accident and emergency department by their parents were compared to
      those consulting their general practitioner. A simultaneous, prospective review
      of these consultations was carried out over a six-week period in an inner-city
      paediatric teaching hospital and a group practice in a socially deprived urban
      area. 730 children less than 13 years of age who presented for a new consultation
      were seen. 629 (86%) presented initially to the general practitioner, who dealt
      with all but 25 (4.0%) without onward referral to the accident and emergency
      department. 127 consultations took place at the accident and emergency
      department, of which 104 (82%) were parental referrals. There was no sex
      difference in children seen by the general practitioner. There was a decreasing
      trend with increasing age in the proportion of children who consulted the general
      practitioner, perhaps due to the higher frequency of injury in the older
      children. Over three quarters (77%) of injured children were brought directly to
      the accident and emergency department, compared with only 4% of children without
      injuries (p < 0.001). Of 22 children with injuries who presented to the general
      practitioner, only 4 (18%) required onward referral. General practitioners met
      the great majority of the paediatric workload generated by the practice. Audit
      between primary and secondary care gives a more reliable picture than data from
      only one source. Injured children are more likely to be taken to the accident and
      emergency department. Further study of the severity of injury in children is
      required to determine if there is potential to reduce parental referrals to
      accident and emergency departments.

PMID- 7502404
TI  - Patterns of admission and discharge in an acute geriatric medical ward.
AB  - Patients admitted to a 30 bedded acute geriatric medical ward in 1993 were
      followed up to discharge. The admission rate on weekend days was half that for
      weekdays. Six percent of ward discharges occurred at weekends, over half being
      due to death. Respiratory, cardiovascular and central nervous systems disorders
      were the commonest reasons for admission (56%) and death (73%). Greater emphasis
      should be placed on discharging patients at weekends.

PMID- 7502405
TI  - Menorrhagia management options.
AB  - A prospective study of the management of menorrhagia in new patients presenting
      to gynaecological outpatients was undertaken at four centres in Northern Ireland
      and two in Great Britain. 325 patients were enrolled, the majority of whom (87%)
      had severe menorrhagia. Patients in all six centres were similar in relation to
      age, marital status, parity, use of contraception and severity of symptoms. 62%
      of the patients were managed medically, improved and were discharged. The rates
      of surgical intervention, in particular in women aged less than 40, appeared
      higher in the Northern Ireland hospitals than Great Britain. There is a need to
      review and audit current practices in the management of menorrhagia.

PMID- 7502406
TI  - Membership by examination.

PMID- 7502407
TI  - From Stoneyford, County Antrim to Coleraine, Australia: Samuel Connor, MD.

PMID- 7502408
TI  - Crohn's disease of the labia minora.

PMID- 7502409
TI  - Crohn's ileitis and salpingo-oophoritis.

PMID- 7502410
TI  - Bilateral subdural collections invisible on a CT brain scan.

PMID- 7502412
TI  - Circumcision in infancy.

PMID- 7502413
TI  - A temperate approach to neonatal circumcision.

PMID- 7502411
TI  - Impact of prostate-specific antigen screening on the natural history of prostate
      cancer.

PMID- 7502414
TI  - The value of screening tests in the detection of prostate cancer. Part I: Results
      of a retrospective evaluation of 1726 men.
AB  - OBJECTIVES: The ratio between free and total prostate-specific antigen (PSA) in
      serum (F/T ratio) was shown to improve the differentiation between prostate
      carcinoma and benign conditions in selected series of patients. In this study the
      F/T ratio was analyzed for its ability to improve the specificity of total serum
      PSA, digital rectal examination (DRE), and transrectal ultrasonography (TRUS) for
      the detection of prostate cancer in an unselected screening population of men
      identified in the Rotterdam population. METHODS: In 1726 men between 55 and 76
      years old, 67 prostate carcinomas were detected by DRE, TRUS, and total serum PSA
      (Abbott IMx, Hybritech Tandem E). The DELFIA ProStatus PSA EQM and ProStatus PSA
      Free/Total assays (Wallac) were applied in retrospect to determine total and free
      serum PSA. Age, total prostate and inner zone volumes were taken into
      consideration. RESULTS: Sixty-seven carcinomas were detected, two by TRUS and
      three by DRE alone. Total serum PSA was the most important single predictor of
      prostate cancer, followed by DRE. The F/T ratio increased the specificity of
      total serum PSA in the PSA range between 4.0 and 10.0 ng/mL. However, this
      improved specificity was not significant, nor for gland volumes restricted to 50
      mL or less. CONCLUSIONS: The combination of total serum PSA and DRE remains the
      standard for detection of prostate carcinoma in a screening population. Their
      specificity may be improved minimally by the F/T ratio, but not significantly in
      a sample of 1726 screened men. The threshold of the F/T ratio, and the optimal
      PSA range for its application, remains to be assessed prospectively.

PMID- 7502415
TI  - The value of screening tests in the detection of prostate cancer. Part II:
      Retrospective analysis of free/total prostate-specific analysis ratio, age
      specific reference ranges, and PSA density.
AB  - OBJECTIVES: The ratio between free and total prostate-specific antigen (PSA) in
      serum (F/T ratio) was shown to improve the specificity of total serum PSA for the
      detection of prostate carcinoma in selected populations. In this study, the value
      of the F/T ratio for screening of prostate cancer was compared with that of age
      specific reference ranges for PSA and PSA density (PSAD) by a simulation
      experiment. METHODS: In 1726 men between 55 and 76 years old, 67 prostate
      carcinomas were detected by application of digital rectal examination (DRE),
      transrectal ultrasonography (TRUS), and total serum PSA. A serum PSA of 4.0 ng/mL
      or more, an abnormal DRE, or an abnormal TRUS were the indications to perform 308
      biopsies. A simulation was performed in which an F/T ratio of 0.20 (ProStatus PSA
      Free/Total), age-specific PSA reference ranges, and a PSAD of 0.12 ng/mL/cc were
      used to study their capability to increase the specificity of total serum PSA in
      predicting prostate biopsy results. RESULTS: Using age-specific PSA reference
      ranges and DRE as indicators for biopsy, a reduction of 37% (113) of biopsies
      would have been obtained with a loss of detected cancers of 12% (11). For the use
      of PSAD and DRE, these numbers were 28% (96) and 11% (7), respectively.
      Application of a serum PSA of 4.0 ng/mL or more and an F/T ratio of 0.20 or less
      and an abnormal DRE as indicators for biopsy would reduce the number of biopsies
      by 37% (112) and the number of detected cancers by 11% (7). The biopsy to
      prostate cancer ratio of these simulations varied between 3.3 and 3.6. Minimal
      loss of cancer detection of 3% (2) with a reduction in the number of biopsies of
      17% (53) is obtained when TRUS is omitted from the screening protocol. Selecting
      men by a total serum PSA value of 2.0 ng/mL for further diagnostic workup by TRUS
      and DRE would have reduced the number of biopsies by 30% (102), and the number of
      cancers detected by 6% (4). CONCLUSIONS: The most cost-effective protocol for
      screening prostate carcinoma appears to be prescreening by total serum PSA. The
      F/T ratio might be used to detect carcinomas in the PSA range below 4.0 ng/mL,
      but the best threshold remains to be assessed.

PMID- 7502416
TI  - Effect of angiotensin-converting enzyme inhibition on nephropathy in patients
      with a remnant kidney.
AB  - OBJECTIVES: This study was performed to evaluate the effect of angiotensin
      converting enzyme inhibitor (ACEI) therapy and dietary protein restriction on
      nephropathy involving a remnant kidney. METHODS: Five patients with proteinuria >
      or = 5 years following partial removal of a solitary kidney were treated with a
      low-protein diet and an ACEI agent. Four patients had biopsy-proven focal
      segmental glomerulosclerosis. The daily urinary protein excretion ranged from
      1240 to 10,032 mg. The serum creatinine levels ranged from 1.2 to 3.1 mg/dL.
      RESULTS: The post-treatment follow-up interval ranged from 18 to 30 months. The
      treatment regimen was well tolerated in all patients. Four patients experienced a
      reduction in the urinary protein level while maintaining stable overall renal
      function. In 1 patient, the urinary protein level increased and renal function
      gradually deteriorated following ACEI therapy. CONCLUSIONS: These preliminary
      data suggest that ACEI therapy and a low-protein diet may mitigate nephropathy
      associated with a remnant kidney.

PMID- 7502417
TI  - Comparison of open and endourologic approaches to the obstructed ureteropelvic
      junction.
AB  - OBJECTIVES: To compare open pyeloplasty with three minimally invasive modalities:
      antegrade endopyelotomy, Acucise endopyelotomy (Applied Medical, Laguna Hills,
      Calif), and laparoscopic pyeloplasty. METHODS: Forty-five adult patients with
      ureteropelvic junction obstruction were managed by one of the above four
      techniques. Success rates, analgesic use, length of hospital stay, recovery time,
      and complications were compared between each of the four groups. RESULTS:
      Successful relief of obstruction was achieved in 100% of patients undergoing open
      and laparoscopic dismembered pyeloplasty, 78% undergoing Acucise endopyelotomy,
      and 77% undergoing antegrade percutaneous endopyelotomy. Acucise endopyelotomy
      results in shorter convalescence (1 week) than antegrade endopyelotomy (4.7
      weeks), laparoscopic pyeloplasty (2.3 weeks) or open pyeloplasty (10.3 weeks).
      Complication rates appear to be similar among all groups. CONCLUSIONS: Our
      limited data imply that Acucise endopyelotomy offers low morbidity with success
      rates comparable to antegrade pyeloplasty, whereas laparoscopic pyeloplasty is as
      effective as open pyeloplasty with diminished morbidity.

PMID- 7502418
TI  - Transitional cell carcinoma of the renal pelvis or ureter: patterns of failure.
AB  - OBJECTIVES: To identify recurrence patterns and possible indications for adjuvant
      treatment. METHODS: Ninety-four patients with transitional cell carcinoma of the
      renal pelvis or ureter were reviewed to determine their pattern of failure.
      Factors including gender and age, tumor stage and grade, and extent of surgical
      procedure and adjuvant radiation therapy (RT) were analyzed with respect to local
      and distant recurrence and survival. RESULTS: Seventy-seven patients had
      resections without residual. On multivariate analysis, grade (P = 0.01) and
      adjuvant RT (P = 0.02) had significant effects on local control. Metastases were
      solely dependent on stage (P = 0.0001). Survival was dependent on stage (P =
      0.0059) and age (P = 0.036), with the use of adjuvant RT of borderline
      significance (P = 0.07). Twenty-seven patients were excluded from local failure
      and survival analysis; of these, 3 died within 1 month of surgery, 5 had
      metastasis at presentation, and 19 had local disease that was unresectable.
      Eleven of these 19 were treated by RT, resulting in 2 long-term disease-free
      survivors after receiving doses of 45 and 50.4 Gy. CONCLUSIONS: In patients with
      adverse factors, such as high grade or stage, close margins, or positive nodes,
      local control can be improved with adjuvant radiation. Improvement in survival is
      of borderline significance on multivariate analysis, with approximately 50% of
      high stage or grade patients developing metastasis.

PMID- 7502419
TI  - Fluorourodynamic and clinical evaluation in males following construction of a
      Kock ileal-urethral reservoir.
AB  - OBJECTIVES: Since 1986, we have offered the option of lower urinary tract
      reconstruction with the Kock ileal-urethral reservoir in selected male patients
      requiring diversion. This study provides insight into the functional
      characteristics of the Kock ileal-urethral reservoir and its effect on
      continence. METHODS: Twenty-four of the initial 225 male patients undergoing this
      procedure at our institution were evaluated by fluorourodynamics within 2 years
      of neobladder construction. Information regarding continence was also obtained by
      means of a patient interview and questionnaire. RESULTS: The average resting
      neobladder pressure was 8.5 cm H2O (range, 0 to 18). Reservoir capacity averaged
      741 cc (range, 225 to 1400). Afferent nipple failure with bilateral grade II
      vesicoureteral reflux was noted in 1 patient (4%). Unsatisfactory daytime
      continence was seen in 2 patients (8%). Unsatisfactory nighttime continence was
      seen in 6 patients (25%). Patient satisfaction was high with an average rating of
      8.6 on a scale of 1 to 10. CONCLUSIONS: Fluorourdynamic data demonstrate a low
      pressure, high-capacity reservoir with a low incidence of reflux. The rate of
      continence is acceptable and patient satisfaction is excellent. The Kock
      ilealurethral reservoir is an excellent alternative to standard diversion for the
      male patient undergoing cystectomy.

PMID- 7502420
TI  - Long-term metabolic and nutritional effects of urinary diversion.
AB  - OBJECTIVES: To evaluate the long-term metabolic and nutritional consequences of
      interposing intestinal segments in the urinary tract. METHODS: Comprehensive
      analyses of blood and urine were performed in 20 patients with conduit urinary
      diversion and in 19 with continent cecal reservoir for urine, all with normal or
      near-normal renal function. The mean follow-up time was 15 years in the conduit
      group and 9 years in the reservoir group. RESULTS: In both patient groups,
      arterial blood gas analysis revealed a tendency to metabolic acidosis with
      respiratory compensation. Although no hyperchloremia was found in either group,
      the mean value of serum chloride was significantly higher (P < 0.05) in the
      reservoir group than in the conduit group. The calciotropic factors, plasma
      lipids, lipoproteins, and liver function values were normal in both groups. Serum
      vitamin B12 levels were subnormal in 3 conduit and 2 reservoir patients, but
      other studied variables of intestinal absorption were within normal limits.
      Conduits utilizing colonic segments showed calcium excretion on the same level as
      in reservoirs, which was significantly higher than in conduits made from ileal
      segments. CONCLUSIONS: Except for increased risk of vitamin B12 deficiency, no
      major adverse metabolic or nutritional effects of conduit or continent urinary
      diversion were found at long-term observation in patients with well-preserved
      renal function. Lifelong surveillance of vitamin B12 levels is necessary in these
      patients.

PMID- 7502421
TI  - Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow
      transplantation.
AB  - OBJECTIVES: To determine the minimal active dose and extent of activity of
      intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow
      transplantation. METHODS: Twenty-four adults with grade 3 or 4 hemorrhagic
      cystitis were treated. All but 2 had failed other local therapy. Treatment was
      initiated at a median of 32 days post-transplant. Eleven patients received
      carboprost intravesicularly at 0.2 mg/dL for 60 minutes every 6 hours, and the
      dose was escalated every 24 hours until a dose of 1.0 mg/dL was reached unless a
      response was achieved. Thirteen additional patients were treated at an initial
      dose of 0.8 mg/dL, with escalation to 1.0 mg/dL after four doses in the absence
      of a response. RESULTS: Overall, 15 of the 24 patients responded. In the dose
      escalation setting, 0.8 mg/dL was the minimal active dose. The total response
      rate was 62% with doses at or above 0.8 mg/dL and 18% at lower doses. All but one
      response occurred with 7 or fewer days of therapy, and 9 patients relapsed later.
      Four additional patients were salvaged following cystoscopy with clot evacuation
      with or without alum or formalin instillation. In all but 1 patient, bladder
      spasms developed during treatment with carboprost, but were not sufficiently
      severe to discontinue therapy. CONCLUSIONS: Intravesicular carboprost at 1.0
      mg/dL every 6 hours for no more than 7 days should be considered for a randomized
      study for treatment of refractory hemorrhagic cystitis. Cystoscopic examination
      and evacuation of clots prior to therapy may be required to achieve the full
      benefit of this treatment.

PMID- 7502422
TI  - Reproducibility of pressure-flow variables in patients with symptomatic benign
      prostatic hyperplasia.
AB  - OBJECTIVES: To study the reproducibility of pressure-flow studies in patients
      with symptomatic benign prostatic hyperplasia and to investigate if the
      reproducibility is influenced by the method of intravesical pressure measurement,
      that is, transurethral catheterization versus suprapubic puncture. METHODS: The
      within-patient variation of maximum urinary flow rates and detrusor pressure at
      maximum flow was investigated in 25 patients in whom 2 (transurethral group) or 3
      (suprapubic group) sequential voidings during urodynamic investigation were
      analyzed. RESULTS: The within-patient variation of pressure-flow values was
      evaluated by the intraclass correlation coefficient, which was 0.71 for maximum
      urinary flow rate and 0.84 for detrusor pressure, suggesting a relatively high
      degree of reproducibility. However in 26% of the patients, the maximum flow rates
      changed by more than 3 mL/s or the detrusor pressure by more than 20 cm H2O
      during the repeated tests. There was no significant difference in the within
      patient variation of pressure-flow values between the suprapubic group and the
      transurethral group. CONCLUSIONS: In larger clinical trials where the assessment
      of treatment effects between groups is desired, a single pressure-flow test is
      sufficient. In the individual patient, a single pressure-flow curve is of limited
      value due to a considerable within-patient variation of the test and, for these
      patients, multiple consecutive tests are recommended for diagnosis of
      intravesical obstruction and assessment of individual patient's response to
      treatment.

PMID- 7502423
TI  - Effect of irrigating fluids and prostate tissue extracts on isolated
      cardiomyocytes.
AB  - OBJECTIVES: A higher mortality probably due to myocardial infarction has been
      demonstrated after transurethral resection of the prostate (TURP) compared with
      open prostatectomy. We used an experimental model system to study the possibility
      that this difference might be due to cardiotoxic effects of two events that
      frequently occur during TURP, namely, dissemination of electrolyte-free
      irrigating fluid and release of prostate tissue substances by electrocutting.
      METHODS: Cardiomyocytes were isolated from male Sprague-Dawley rats. Cell
      morphology and viability were examined repeatedly during 3 hours of incubation.
      Control experiments were compared with 34 preparations mixed with one of five
      different irrigating fluids and with 28 preparations mixed with a prostate
      extract, either from the same rat or from patients undergoing TURP. RESULTS: Most
      irrigating fluids reduced the viability of the myocytes. The fraction of viable
      cells in the incubation mixture averaged 83% (glycine 1.5%), 88% (glycine 1.5%
      plus ethanol 1%), 92% (glycine 2.2%), 92% (mannitol 3% plus ethanol 1%), and 99%
      (sorbitol 2% plus mannitol 1%) of that found in the respective control
      incubations. In contrast, the prostate extracts did not decrease the viability of
      the cardiomyocytes. Extract from the rats even seemed to have a trophic effect.
      CONCLUSIONS: Our results show that electrolyte-free irrigating fluids but not
      prostate extracts have mild cardiotoxic properties. This opens up the possibility
      that fluid absorption during TURP has a devitalizing effect on the heart.

PMID- 7502424
TI  - Removal of the financial barrier to health care: does it impact on prostate
      cancer at presentation and survival? A comparative study between black and white
      men in a Veterans Affairs system.
AB  - OBJECTIVES: African-American men are known to have a higher incidence and
      mortality rate from prostate cancer than American-Caucasian men. It is also known
      that African Americans have a higher incidence of advanced stage disease at
      diagnosis. One hypothesis for the latter is a delay in diagnosis due to lack of
      financial access to health care. Because eligibility for medical care in Veterans
      Affairs Medical Centers (VAMCs) is similar for both black and white patients,
      less disparity of stage at diagnosis, and therefore survival between blacks and
      whites, would be expected. METHODS: Cases for this study included only those
      histologically confirmed, newly diagnosed prostate cancers at the Allen Park VAMC
      in Wayne County, Michigan, between 1973 and 1992. Trained Surveillance,
      Epidemiology, and End Result (SEER) abstractors determined the stage at
      diagnosis, according to SEER criteria. Data analyses include descriptive
      statistics and survival analysis. RESULTS: The distribution of race and annual
      income of all male patients seen at the VAMC in Allen Park is similar. Over the
      entire 20-year period (1973 to 1992), there were a total of 358 prostate cancers
      in white patients and 383 in black patients. The ages of black and white patients
      were comparable. The proportion of white and black men presenting with localized
      disease is similar (57% and 54%, respectively). A significantly greater
      proportion of black patients with prostate cancer were classified as having
      distant disease compared with white patients (25% versus 19%; P = 0.045). A
      racial "crossover" effect in survival occurred around age 70 years, with white
      men demonstrating improved survival under 70 years of age, and black men 70 years
      and older tending to have better survival. CONCLUSIONS: These data suggest that
      financial access to care has no apparent influence on the higher proportion of
      distant disease and poorer survival of African-American patients with prostate
      cancer compared with American-Caucasian men.

PMID- 7502425
TI  - The influence of prostate size on cancer detection.
AB  - OBJECTIVES: To determine if cancer detection rates vary with prostate size using
      a sextant core biopsy pattern. METHODS: We reviewed 1021 transrectal ultrasound
      (TRUS)-guided sextant pattern prostate biopsies to determine if cancer detection
      varied based on prostate size. Prostate size was determined using a computer
      generated elliptical estimation method. Sextant core biopsies were taken, and the
      patients divided into groups based on estimated size of the prostate and biopsy
      outcome. Large prostates were those that were estimated by TRUS as 50 cc or more.
      Prostates were considered small if they were less than 50 cc. Groups were
      compared based on size and biopsy outcome. RESULTS: Adenocarcinoma was detected
      in 33% (334 of 1021) of the patients. Large prostates were noted in 34% (346 of
      1021), of which 23% (80 of 346) had cancer detected by sextant biopsy. Small
      prostates were noted in 66% (675 of 1021), of which 38% (254 of 675) had cancer
      detected. The difference in cancer detection in large and small glands using a
      sextant pattern was statistically significant (P < 0.01). Patients with positive
      biopsies had significantly smaller prostate sizes (40 cc +/- 26) when compared
      with those with negative biopsies (51 cc +/- 33) (P < 0.01). Only 14% (8 of 58)
      of patients with gland sizes 100 cc or greater had positive sextant biopsies
      while 49% (118 of 239) with prostates 25 cc or less had cancer detected.
      Multivariate statistical analysis was used to control for differences in age,
      prostate-specific antigen (PSA), PSA density, TRUS findings, and digital rectal
      examination between the large and small prostate groups. The difference in cancer
      detection persisted (P < 0.05) CONCLUSIONS: Currently no evidence exists to
      support differing cancer rates based on gland size alone. Our cancer detection
      rate using a sextant pattern was higher in men with prostates less than 50 cc,
      and patients diagnosed with cancer had significantly smaller prostates than those
      with a negative sextant biopsy. Our data suggest that significant sampling error
      may occur in men with large glands, and more biopsies may be needed under these
      circumstances. The effects of tumor volume, focality, and specimen size in
      relation to overall gland size may contribute to these findings.

PMID- 7502426
TI  - Chromosomal anomalies in atypical adenomatous hyperplasia and carcinoma of the
      prostate using fluorescence in situ hybridization.
AB  - OBJECTIVES: The genetic alterations of atypical adenomatous hyperplasia (AAH) of
      the prostate, a possible precursor of prostate adenocarcinoma, have not been
      previously investigated. METHODS: We used fluorescence in situ hybridization with
      centromere-specific probes for chromosomes 7, 8, 10, 12, and Y to evaluate
      chromosomal anomalies in atypical adenomatous hyperplasia (23 foci) and
      adenocarcinoma (31 foci) in 19 whole-mount radical prostatectomy specimens.
      RESULTS: Chromosomal anomalies were found in 2 foci (9%) of AAH and 17 foci (55%)
      of carcinoma. There was no relationship between the chromosomal anomalies in AAH
      and matched foci of carcinoma. CONCLUSIONS: These findings indicate that AAH is
      not obviously linked genetically to prostate cancer, although it occasionally
      contains chromosomal anomalies.

PMID- 7502427
TI  - Recombinant adenovirus vector expressing wild-type p53 is a potent inhibitor of
      prostate cancer cell proliferation.
AB  - OBJECTIVES: A recombinant adenovirus vector (AdWTp53) expressing wild-type p53
      was evaluated for its cell growth inhibitory effects on metastatic human prostate
      cancer cells. METHODS: Human prostate cancer cells LNCaP, DU145, PC3, 1LN, and
      DUPro-1 were infected with AdWTp53 vector and expression of exogenous p53 in
      these cells was analyzed by immunoprecipitation and western blot assays. The cell
      growth inhibitory effects of AdWTp53 were determined by counting cell number on a
      hemocytometer or by crystal violet staining of cells after infection with
      AdWTp53. The p53-regulated gene WAF1 and DNA fragmentation were also analyzed in
      prostate cancer cells infected with AdWTp53. RESULTS: High levels of the AdWTp53
      vector-derived p53 protein were present in metastatic prostate cancer cells, and
      the p53-regulated gene WAF1 was induced in these cells. Infection of these tumor
      cell lines with AdWTp53 vector resulted in severe growth inhibition and cell
      death in comparison to untreated or control adenovirus vector-infected cells.
      Furthermore, fragmentation of genomic DNA, a property associated with apoptosis,
      was also observed in prostate cancer cells infected with AdWTp53. CONCLUSIONS:
      AdWTp53 vector exhibited a potent inhibitory effect on the growth of all of human
      metastatic prostate cancer cells, and both cytostatic and cytotoxic effects of
      AdWTp53 were observed. The induction of p53-regulated gene WAF1 in AdWTp53
      infected prostate cancer cells suggests the involvement of cellular p53 pathway
      in the cell growth inhibition. These results provide a molecular basis for
      further evaluation of antitumorigenic effects of AdWTp53 vector in animal models
      of prostate cancer.

PMID- 7502429
TI  - Efficacy of the vacuum constriction device in patients with corporeal venous
      occlusive dysfunction.
AB  - OBJECTIVES: The vacuum constriction device (VED) is an effective nonsurgical
      treatment for erectile dysfunction. Its efficacy in specific patient groups,
      however, has not been extensively studied. Only one study to date has examined
      the use of the VED in patients with corporeal veno-occlusive dysfunction (CVOD).
      This study used a mailed questionnaire and no statistical analysis of the data.
      The purpose of this study was to examine the efficacy of the VED in patients with
      documented CVOD. METHODS: From 1989 to 1992, 294 patients chose to use a VED as
      treatment for erectile dysfunction. All patients were evaluated with a thorough
      history and physical examination, hormonal testing, glucose tolerance testing,
      and nocturnal penile tumescence studies. Ninety-eight patients underwent
      additional vascular testing. When seen in follow-up, patients were asked to
      assess erection quality and overall satisfaction with the device. RESULTS: Fifty
      patients had documented CVOD (33 by cavernosometry, 16 by ultrasound, and 1 by
      cavernosography). Twenty-eight patients (56%) were satisfied, 13 patients (26%)
      were unsatisfied, and in 9 patients (18%) satisfaction could not be determined.
      Thirty-eight patients (76%) achieved an erection of at least 7 on a scale of 1 to
      10. There was no relationship between the severity of disease (as measured by
      cavernosometry) and the rating of erection (Kruskal-Wallis test, P = 0.77) or
      satisfaction with the device (Fisher's exact test, P = 0.95). CONCLUSIONS: The
      VED is an acceptable nonsurgical treatment for patients with erectile dysfunction
      secondary to CVOD regardless of severity. Its success rate is comparable to other
      therapeutic modalities such as injection therapy.

PMID- 7502428
TI  - Single-agent therapy with bicalutamide: a comparison with medical or surgical
      castration in the treatment of advanced prostate carcinoma.
AB  - OBJECTIVES: Single-agent therapy with bicalutamide, a nonsteroidal antiandrogen,
      was compared with castration, either surgical or medical, in patients with
      untreated Stage D2 prostate cancer. METHODS: In an open, randomized, multicenter
      trial, patients were randomized to treatment with 50 mg bicalutamide (n = 243)
      once daily or to castration (n = 243), either orchiectomy or depot injection of
      goserelin acetate every 28 days. Primary efficacy endpoints were times to
      treatment failure and objective disease progression and survival. Assessments
      included review of measurable metastases, prostate dimensions, Eastern
      Cooperative Oncology Group performance status, pain, analgesic requirements, and
      quality of life responses. RESULTS: The median duration of therapy was 39 weeks
      for bicalutamide-treated patients and 42 weeks for castrated patients; treatment
      failure occurred in 53% and 42% and disease progression in 43% and 33%,
      respectively. Treatment effects favored castration for both endpoints (P < or =
      0.002), with hazard ratios (bicalutamide:castration) of 1.54 (95% confidence
      interval [CI], 1.18 to 2.00) for time to treatment failure and 1.6 (95% CI, 1.19
      to 2.15) for time to disease progression. From the 1-year survival analysis, the
      hazard ratio for probability of death was 1.29 (95% CI, 0.96 to 1.72). Thus far,
      with a median follow-up of 86 weeks, median survival has not been reached in
      either group. Changes from baseline in several quality of life variables were
      significantly different (P < or = 0.01) between treatment groups periodically
      from months 1 to 6, and all favored bicalutamide. Overall, the antiandrogen was
      well tolerated compared with castration; with bicalutamide, hot flushes occurred
      less often and breast tenderness and gynecomastia more often. CONCLUSIONS:
      Although a dosage of 50 mg of bicalutamide once daily was not as effective as
      castration, the favorable quality of life outcomes and the low incidence of
      nonhormonal adverse events provide reasons to evaluate bicalutamide, as a single
      therapeutic agent, at higher doses.

PMID- 7502430
TI  - Ureterolithotripsy in children.
AB  - OBJECTIVES: The pediatric application of ureteroscopy was initially hindered by
      the size of the instruments and the fear of damaging the urethra and
      ureterovesical junction during endoscopic maneuvers. This review of our
      experience is focused on the usefulness of thin and ultrathin ureteroscopes such
      as the 7 F Gautier rigid ureteroscope with rod lens optics (Wolf) or the new,
      ultrathin 4.8 F Wolf ureteroscope, semirigid, fiberoptic, in conjunction with
      atraumatic sources of energy such as pulsed dye laser or ballistic lithotripter,
      for the treatment of ureteral stones in children. METHODS: Between 1989 and 1994,
      we performed ureteroscopy and ureterolithotripsy on 7 children less than 10 years
      old. There were 6 male patients and 1 female patient, with a mean age of 6 years
      (range, 3.5 to 10). We used the pulsed dye laser Pulsolith and the ballistic
      lithotripter Lithoclast, the Gautier (Wolf) rigid, rod lens ureteroscope (7 F),
      without the sheath or the blunt needle 4.8 F semirigid (Wolf), fiberoptic
      ureteroscope. In all cases a double pigtail ureteral catheter was left in situ.
      RESULTS: In all 7 cases, the treatment was successful without early or delayed
      complications. In particular, no case of vesicoureteral reflux was observed in
      any of the children during subsequent follow-ups. CONCLUSIONS: This article
      demonstrates the feasibility of ureteroscopy and ureterolithotripsy in children
      less than 10 years old with ureteral stones. We believe that because of the
      fragility of the ureter in the pediatric age group, ureteroscopic maneuvers
      should be performed and handled by experienced endourologists in well-equipped
      centers.

PMID- 7502431
TI  - A child with an intra-abdominal testicular teratoma: a case report and review of
      prepubertal cryptorchid germ cell tumors.
AB  - OBJECTIVES: We report the case of a tumor in an intra-abdominal cryptorchid
      testis of a 7-month-old male infant. Torsion of a testicular teratoma was
      confirmed by pathologic examination. A review was undertaken to identify and
      characterize other reports of prepubertal cryptorchid germ cell neoplasms.
      METHODS: Cases of testicular germ cell neoplasms in association with
      cryptorchidism in phenotypically normal males were identified through a MEDLINE
      search of the English literature and review of published bibliographies. RESULTS:
      A total of 14 cases were identified with testis location provided in 12 patients.
      Half of the neoplasms were located in abdominal testis, and all of these were
      associated with torsion, although 2 of 6 patients were asymptomatic. Two patients
      had tumors in the contralateral normally descended testis. Teratoma was the most
      frequently encountered tumor type. CONCLUSIONS: Characteristics of prepubertal
      cryptorchid testicular germ cell tumors reflect those seen in post-pubertal
      cryptorchid tumors in location but differ in histologic type. Possible
      pathogenesis is discussed. Follow-up was not provided in all cases although
      outcome appears to be good. We believe that these lesions are likely
      underreported.

PMID- 7502432
TI  - An alternative surgical technique for the management of afferent limb structure
      in Kock pouch continent urinary diversion.
AB  - Stenosis of the afferent limb has recently been recognized as a rare cause of
      upper urinary tract obstruction in patients with a Kock pouch continent urinary
      diversion. Usually, it can be managed by endoscopic balloon dilation but
      occasionally open surgical reconstruction is required. We describe an alternative
      simpler surgical technique that was used in a patient who presented with anuria
      due to afferent limb stenosis 13 years after the construction of a Kock pouch
      continent urinary diversion.

PMID- 7502433
TI  - Successful transplantation of a kidney with early membranous nephropathy.
AB  - This report describes a patient with end-stage renal disease secondary to long
      standing type II diabetes mellitus who received a cadaveric renal transplant from
      a 37-year-old woman who died of massive cerebral infarction. An autopsy performed
      on the donor following organ procurement revealed no obvious contraindications to
      transplantation. A renal biopsy of the donor kidney performed at the time of
      transplantation, however, subsequently showed early membranous nephropathy by
      electron microscopy. There was immediate graft function and the recipient
      continues to have good renal function 3 years post-transplantation.

PMID- 7502434
TI  - Bilateral renal oncocytomatosis in a patient with renal failure.
AB  - Bilateral multifocal renal oncocytomas are very rare disorders with only 6
      previously reported cases in the world literature, of which only 3 have had
      pathologic confirmation. We present the first reported case of diffuse,
      bilateral, multifocal renal oncocytomatosis in a patient with end-stage renal
      disease requiring hemodialysis. Our patient was found to have hundreds of nodular
      tumors in both kidneys on exploration, representing the second such reported
      finding.

PMID- 7502435
TI  - Leiomyosarcoma of the vena cava with atrial extension: long-term survival
      following resection and caval replacement without circulatory arrest.
AB  - This is a case report of a primary vena cava sarcoma extending to the atrium in a
      young woman, which was resected. Cardiopulmonary bypass was used, and the cava
      replaced with ringed Gore-Tex. She remains alive and well more than 3 years after
      the surgery with no evidence of recurrence.

PMID- 7502436
TI  - Laparoscopic diagnosis and management of transverse testicular ectopia.
AB  - Transverse testicular ectopia (TTE) is a rare genitourinary anomaly. We report a
      case of TTE in a 14-year-old boy diagnosed and managed laparoscopically. The
      clinical features and etiology of this rare testicular anomaly are reviewed.

PMID- 7502437
TI  - Testicular dysmorphism associated with abdominoscrotal hydroceles during infancy.
AB  - Abdominoscrotal hydrocele (ASH) in infancy is a rarely reported condition. We
      present an 11-week-old infant who was born with massive scrotal enlargement. At
      exploration, he was found to have large bilateral ASHs and bilateral fusiform
      testes. Gross morphologic testicular changes associated with hydrocele have
      previously only been reported in adults. Our patient is the youngest to be
      reported with ASHs.

PMID- 7502438
TI  - Successful management of intracardiac extension of tumor thrombus in a patient
      with advanced nonseminomatous germ cell testicular cancer.
AB  - A young patient with testicular germ cell tumor presenting with inferior vena
      cava thrombus extending into the right heart with free-floating thrombus in the
      right ventricle and a simultaneous epidural spinal cord compression is presented.
      Due to the perceived high risk of embolization and the urgent need to begin
      systemic chemotherapy, he was managed with tumor thrombectomy utilizing
      cardiopulmonary bypass and hypothermic circulatory arrest followed shortly
      thereafter by systemic chemotherapy. There were no perioperative complications,
      and he is alive and without recurrence 24 months following four cycles of
      systemic chemotherapy.

PMID- 7502439
TI  - Molecular advances in pediatric urology.

PMID- 7502440
TI  - A controlled trial of bicalutamide versus flutamide, each in combination with
      luteinizing hormone-releasing hormone analogue therapy, in patients with advanced
      prostate cancer.

PMID- 7502441
TI  - Gore-Tex in bolstering closure of renal parenchyma defects.

PMID- 7502442
TI  - Cryoablation of the prostate.

PMID- 7502443
TI  - Cryoablation of the prostate.

PMID- 7502444
TI  - [Implantation microsurgery in the phoniatric practice].
AB  - The paper reports the results of teflon paste implantation into the vocal folds
      of 368 patients with laryngeal unilateral paralysis and scar deformities, atrophy
      of vocal muscles. Implantation of teflon paste polytef produces a high functional
      effect in unilateral laryngeal paralysis. 38 patients underwent implantation with
      collagen. The response of the adjacent tissues to collagen injection is minimal
      positively comparing to teflon. However, 10 patients needed more injections of
      liquid collagen 6-18 months following the initial administration because of
      collagen metabolism.

PMID- 7502445
TI  - [Combined treatment of malignant tumors of the external auditory canal and the
      middle ear].
AB  - Clinical outcomes have been analyzed for 50 patients with malignant tumors in the
      external acoustic meatus (EAM) and the middle ear (ME). The patients have
      received combined therapy with pre- or postoperative radiation. Combined
      treatment for EAM and ME cancer is a method of choice which increases survival of
      patients and improves quality of their lives. In primary cancer of the ear
      preoperative radiation is preferable, while postoperative radiation is required
      in advanced disease, in moderately or poorly differentiated tumors when the risk
      of recurrence is especially high.

PMID- 7502446
TI  - [Recurrences of chemodectomas and hemangiomas of the ear: their diagnosis and
      treatment].
AB  - Chemodectomas and hemangiomas of the ear account for 53.9% of overall occurrence
      of benign tumors of the ear. Recurrences are also a frequent finding. The leading
      treatment approach is surgical. The recurrences are managed surgically in
      combination with cryotherapy delivered by means of optic quantum generators.
      Follow-up of 45 patients established the maximal time of recurrence onset--10
      years. Tumors which arise later should be considered as metachronous multifocal.

PMID- 7502447
TI  - [Laser surgery in laryngeal diseases in children (preliminary report)].
AB  - YAG-Nd-laser Raduga-1 was employed in 25 operations performed in 22 children for
      scarring stenosis, papillomatosis and vascular tumors of the larynx, oropharynx
      and trachea. Contact irradiation resulted in 1 serious complication only which
      was successfully corrected. The technique may be used for removal of vascular
      tumors, recanalisation of the larynx in massive scars.

PMID- 7502448
TI  - [Antibodies to alpha-2A interferon in children with juvenile respiratory
      papillomatosis].
AB  - Follow-up of 36 JRP children and 12 controls (as shown by solid-phase enzyme
      immunoassay) has revealed that antibodies to IFN-alpha 2a with titers 1:20 to
      1:1280 were present in 73.7% (14 of 19) of patients after interferon therapy and
      in 5.8% (1 of 17) of those who have not received interferon. None of the controls
      had the antibodies. Among the patients who have received only recombinant IFN
      alpha 2a 88.8% carried the antibodies. In leukocytic interferon-treated group
      this number made up 20%. The primary results evidence that there is no negative
      effect of INF antibodies on the treatment results in the doses and schemes used.
      Positive results of INF in JRP were not reported either.

PMID- 7502449
TI  - [Angiofibroma of the base of the skull in children].
AB  - Throughout 1988-1993 ENT surgeons from the Central Pediatric clinic operated on
      35 children aged 3-14 years for angiofibroma of the base of the skull. The
      majority of the cases were advanced with involvement of all the paranasal
      sinuses. The tumor has invaded the orbit, pterygopalatine, infratemporal, middle
      cranial fossa, cavernous sinus and internal carotid artery in 5, 7, 3, 5 and 1
      children, respectively. The removal of the tumor was carried out through nasal
      maxillary approach without carotid artery ligation. A cosmetic suture was placed
      subsequently. Anesthetic management has been elaborated. 3 children responded
      well to radiotherapy. Angiofibroma recurrence occurred in 5 children, in 3 of
      them after endonasal removal.

PMID- 7502450
TI  - [Mechanisms of interactions between different types of nystagmus].
AB  - Basing on the original and literature data it is suggested that all types of
      nystagmus are formed by the same complex system. Under combined stimulation,
      impulses from the sensory systems are integrated not only in the vestibular
      nuclei, but also in a series of structures at cortical-subcortical level. The
      integration proceeds with its own polarity (activating or inhibiting) when a
      signal alters the ability of a structure to respond to another inputting signal.
      In this way the thresholds are permanently modified in the integrating structures
      of the system. It results in increasing or decreasing effect of the outputting
      reaction of the system. Final response of integrating process reaches the
      effector level of the nystagmus generation, namely paramedial or mesencephalic
      regions of pontine reticular formation and spreads further to oculomotor nuclei.

PMID- 7502451
TI  - [Finger test as a prognostic criterion in the assessment of the effectiveness of
      treatment of patients with tinnitus].
AB  - ENT specialists of the Moscow Sechenov Medical University have developed and
      tried a variant of the pointed test permitting prognostication of the results
      which could be obtained at treatment of patients with noise in the ears of
      different etiology. The test was performed in 263 patients with neurosensory,
      mixed-type and conductive hypoacusis. High informative potential, convenience in
      performance for physician and the patient who can be taught to conduct in
      independently make the test valuable in practical otorhinolaryngology.

PMID- 7502452
TI  - [Possibilities of helium-neon lasers in olfactory disorders].
AB  - 310 patients with olfactory analyzer dysfunction have been examined. Of them 40
      patients received laser radiation on the olfactory zone. The course comprised 10
      sessions. A response occurred in 26 patients who exhibited neither side effects
      nor allergy. The conclusion is made on validity of using helium-neon laser in
      perspective olfactory defects.

PMID- 7502453
TI  - [Reconstruction of the ossicle-tympanic system with a variable configuration
      prosthesis].
AB  - The author offers a prosthesis with variable internal configuration made of human
      fetus flat bone. The prosthesis is intended for ossicle tympanoplasty in chronic
      otitis media when total and subtotal destruction of the auditory ossicle takes
      place and in partial defect of the lateral attic wall. The design warrants
      adjustment to different area of the tympanic ring region. Morphological and
      functional outcomes of the reconstruction are satisfactory.

PMID- 7502454
TI  - [Dirithromycin, a new antibiotic in the treatment of pharyngeal inflammation].
AB  - The trial of a new antibiotic dirithromycin against acute pharyngitis and
      tonsillitis for safety and efficacy included 28 patients with acute tonsillitis
      and pharyngitis. Microbiological, biochemical, clinical and laboratory tests were
      conducted throughout the treatment and 2-3 weeks after the end of dirithromycin
      administration. The results support dirithromycin clinical potential in acute,
      chronic pharyngeal inflammation due to its high selective activity in relation to
      beta-hemolytic streptococcus A and the absence of side effects.

PMID- 7502455
TI  - [Postoperative care of patients after radical surgery of the maxillary sinus].

PMID- 7502456
TI  - [Lomuzol in the treatment of allergic rhinitis].
AB  - The response to lomuzol was registered in 37 out of 39 patients with allergic
      rhinitis given lomuzol. In 16 patients the response was complete, in 14 partial,
      in 7 satisfactory. In 6 patients of placebo no effect was recorded. The drug
      proved uneffective in hypertrophy of the turbinate bones.

PMID- 7502457
TI  - [The role of focal infection in the pathogenesis and present-day approaches to
      therapeutic policy in chronic tonsillitis].

PMID- 7502459
TI  - [A case of retropharyngeal abscess in an adult].

PMID- 7502458
TI  - [Nasopharyngeal teratoma in a newborn].

PMID- 7502460
TI  - [Methods of active teaching (practical game, discussion) at the
      Otorhinolaryngology Department].
AB  - Active methods of education (business games and discussions) have been
      successfully tried at the chair of otorhinolaryngology for development of
      occupational and communication skills in ENT students. When added to standard
      training methods, the above ones may contribute significantly to completeness of
      future doctors' professional knowledge. Methodology of business games and
      discussion preparation and performance, relevant topics, difficulties and
      approaches to their overcoming are detailed.

PMID- 7502461
TI  - [Problems of organization and prospects of outpatient and inpatient ENT services
      in Moscow].

PMID- 7502462
TI  - Developments in diagnosis: a review of the CVL's centenary year.

PMID- 7502464
TI  - Effects of current and waveform on the incidence of breast meat haemorrhages in
      electrically stunned broiler chicken carcases.
AB  - The effects of the current and its waveform on the prevalence of broken bones and
      breast meat haemorrhages in electrically stunned broiler chickens were examined
      at two poultry processing plants. Increasing the current over the range from 68
      to 115 mA per bird had very little effect on the carcase quality, but increased
      the incidence of broken furculum and coracoid bones in birds stunned with a
      sinusoidal alternating current (AC). Clipping a sinusoidal AC with a thyristor
      had a pronounced effect on the carcase quality, and resulted in more broken bones
      and breast meat haemorrhages.

PMID- 7502466
TI  - Use of ammonium chloride in falconry in the Middle East.

PMID- 7502463
TI  - Nephrotoxicity of Narthecium ossifragum in cattle in Norway.
AB  - During the summer of 1992 renal failure was diagnosed in 232 grazing cattle in 85
      herds on the west coast of Norway. The salient clinical signs were depression,
      anorexia and melaena or fresh blood in the faeces; diarrhoea was also commonly
      observed. The serum concentrations of creatinine, urea, magnesium and phosphorus,
      and the activities of glutamate dehydrogenase, aspartate aminotransferase and
      creatine kinase were above normal and the serum calcium concentration was below
      normal. Post mortem examinations consistently revealed renal tubular necrosis. In
      some cases there was liver necrosis and also erosions at the base of the tongue,
      in the oesophagus and in the jejunum and colon. The toxicity was probably caused
      by the plant Narthecium ossifragum (bog asphodel).

PMID- 7502465
TI  - Immunoprophylaxis of caprine contagious agalactia due to Mycoplasma agalactiae
      with an inactivated vaccine.
AB  - The aim of this study was to control endemic contagious agalactia due to
      Mycoplasma agalactiae in a semi-extensive goat herd by means of vaccination with
      an inactivated vaccine. Groups of 400 goats were vaccinated one month before and
      three months after parturition (group A), one month before and four months after
      parturition (group B), and two months and one month before and three months after
      parturition (group C). The experiment continued over six lactations and natural
      infections were monitored clinically, immunologically and microbiologically.
      After the sixth lactation there were no significant clinical differences between
      these two groups and group C. The levels of growth-inhibiting antibodies ranged
      from 1:20 to 1:80 in groups A and B and from 1:40 to 1:160 in group C. The
      numbers of goats excreting mycoplasmas decreased to a greater extent in group C
      than in groups A and B. A natural infection induced an outbreak of contagious
      agalactia in group B. An experimental infection with 10(6) cfe affected seven of
      10 goats in group A (two seriously) and two goats in group C moderately. It is
      recommended that three doses of vaccine should be administered before, and one
      dose after each parturition, and that the herd should be kept isolated in order
      to control the disease.

PMID- 7502468
TI  - Two cases of pyloric adenocarcinoma in the ferret (Mustela putorius furo).

PMID- 7502469
TI  - Isolation of Yucaipa virus.

PMID- 7502467
TI  - Crenosoma vulpis, the fox lungworm, in dogs.

PMID- 7502470
TI  - The cascade.

PMID- 7502471
TI  - Ultrasonographic examination of the small intestine of cows with ileus of the
      duodenum, jejunum or ileum.
AB  - The small intestine of 35 heifers and cows with an ileus of the duodenum, jejunum
      or ileum was examined ultrasonographically. After a clinical examination, the
      animals were examined from the right flank and thorax with a 3.5 MHz linear
      transducer, and the findings were verified by a right flank laparotomy or post
      mortem. Dilated loops of small intestine with a diameter of more than 3.5 cm were
      visible in at least one location in all the animals; they were seen predominantly
      in cross-section or longitudinally. The number of loops of dilated intestine
      visible from the flank or intercostal spaces was markedly influenced by the site
      of the ileus. In animals with an ileus of the duodenum, only one intestinal loop
      was usually visible from the flank or from the 12th, 11th or 10th intercostal
      spaces. In contrast, more than five dilated loops of intestine were usually
      visible in animals with an ileus of the jejunum or ileum. The largest diameter of
      intestine measured from the 12th intercostal space was between 6.5 and 9.9 cm in
      animals with an ileus of the duodenum, between 3.5 and 9.8 cm in animals with an
      ileus of the jejunum, and between 4.4 and 5.5 cm in animals with an ileus of the
      ileum. In the majority of the cows, the contents of the intestines were
      predominantly echogenic, but in the others they were anechoic. The cause of the
      ileus could be identified by ultrasonography in only a few cases.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7502472
TI  - Analysis of the causes of high rates of carcase rejection at a poultry processing
      plant.
AB  - A poultry processing plant received approximately 33.65 million birds from 87
      commercial broiler growing units in 1992. Carcase rejection rates of 3 per cent
      or more were recorded in birds received from 13.2 per cent of the rearing houses
      distributed among 48 per cent of the growing units. The higher rates of carcase
      rejection were found on the units with an average flock size of over 100,000
      birds and from rearing houses with a population of more than 30,000 birds. The
      main causes of rejection were birds dead on arrival, disease and miscellaneous
      conditions. The average rates of carcase rejection for birds dead on arrival and
      disease were higher on the units with a high rejection rate than on the others.
      The commonest cause of carcase rejection due to disease was colisepticaemia.

PMID- 7502473
TI  - A preliminary re-assessment of the requirements for major minerals by growing
      pigs.
AB  - Forty-two mineral balances were measured in 50 kg pigs fed various diets,
      including barley, maize or potato, and used to examine the presumption that the
      current recommended dietary requirements for the major minerals, especially
      phosphorus, are essential to the well-being of the pig. All the diets contained
      similar levels of all the mineral elements, except potassium which was higher in
      the diets containing potato. The concentrations/kg dry matter were 11.0 g
      calcium, 6.9 g phosphorus, 0.96 g sodium, 1.5 g magnesium and 5.4 g potassium or
      14.0 g potassium in the diets containing potato. The apparent digestibility
      coefficients were calcium 0.39, phosphorus 0.46, sodium 0.72, magnesium 0.26 and
      potassium 0.70 or 0.80 and the gross efficiencies with which the ingested
      elements were retained were calcium 0.36, phosphorus 0.25, sodium 0.32, magnesium
      0.07 and potassium 0.22 or 0.16. The low efficiencies of utilisation of the
      digested minerals, especially phosphorus (0.53), suggested that a reduction in
      dietary phosphorus levels may be justified in terms of reducing the pollution of
      the environment with phosphorus caused by the application of pig slurry.

PMID- 7502474
TI  - Suspected gangrenous ergotism in a wild roe deer (Capreolus capreolus).

PMID- 7502475
TI  - Intestinal obstruction in a blue-faced Leicester ram associated with a
      phytobezoar lodged at the pelvic inlet.

PMID- 7502476
TI  - Bovine neosporosis in Zimbabwe.

PMID- 7502477
TI  - Castration and/or tail docking of lambs.

PMID- 7502478
TI  - Prescription of veterinary drugs in fish farming.

PMID- 7502479
TI  - Control of sheep scab.

PMID- 7502480
TI  - Gastric foreign body in a horse.

PMID- 7502481
TI  - Live animal exports.

PMID- 7502482
TI  - Effect of BVD virus infection on alveolar macrophage functions.
AB  - Alveolar macrophages (AM) were recovered by bronchoalveolar lavage from a group
      of eight calves at various times before and after inoculation with a cytopathic
      respiratory isolate of bovine viral diarrhoea virus (BVDV). A second group of
      four calves were given tissue culture medium as a control inoculum. Macrophages
      were also recovered from two additional, uninoculated calves, and were exposed to
      BVDV in vitro. Tests were carried out on the recovered macrophages to determine
      the effects of the virus on several functional properties. Immunofluorescence did
      not indicate the AM as being readily susceptible to this isolate of BVDV,
      although infection did occur. Fc receptor (FcR) and complement receptor (C3R)
      expression, phagocytosis and microbicidal activity and the production of
      neutrophil chemotactic factors were all significantly reduced in macrophages
      recovered from BVDV infected calves, compared with pre-inoculation control
      levels, whereas the control inoculated calves displayed significant increases in
      some of the functions. With macrophages exposed to the virus in vitro however,
      only FcR and C3R expression and phagocytic activity were significantly reduced.
      The results demonstrate that BVDV can reduce local immune defences in the lung,
      following infection by the respiratory route, and in conjunction with the other
      immunosuppressive properties of BVDV would favour a pre-disposing role for the
      virus in the pathogenesis of respiratory disease in calves.

PMID- 7502483
TI  - Preparation and characterization of monoclonal antibodies against bovine
      myeloperoxidase.
AB  - We established eight cloned B-cell hybridomas producing monoclonal antibodies (Mo
      abs) against bovine myeloperoxidase (MPO). These anti-MPO (AM) Mo abs, designated
      AM1-AM8, all reacted similarly to three chromatographic forms of MPO, isolated
      from a single donor, in an enzyme linked immunosorbent assay. According to
      immunoblot analysis and ELISA the AM Mo abs are specific to bovine MPO and show
      no cross reactivity with other neutrophil granule proteins such as lactoferrin,
      lactoperoxidase and serum albumin. In immunoblot analyses IgG1 class AM1, AM2,
      AM3 and AM4 Mo abs immunostained the heavy subunit of the MPO (57 kDa).
      Additionally, the AM Mo abs seem to bind either the reactive site or epitopes on
      bovine MPO that affect the peroxidase activity of this enzyme. AM Mo abs reacted
      specifically with neutrophils but did not react with lymphocytes or epithelial
      cells. The present study shows that these AM Mo abs could be used for developing
      immunoassays to measure bovine MPO from biological fluids and for localizing
      neutrophils at sites of infections. They could also be useful in studies
      assessing the involvement of MPO in inflammatory processes in bovine species.

PMID- 7502484
TI  - Mast cell tryptase levels in normal canine tissues.
AB  - Levels of canine tryptase from various tissues were quantified using a
      competition enzyme-linked immunosorbent assay (ELISA). The assay utilises an
      affinity-purified rabbit anti-tryptase antibody in the solid phase and alkaline
      phosphatase conjugated tryptase together with unlabelled tryptase in the fluid
      phase. The assay will rapidly quantify 40-5000 ng ml-1 of tryptase in tissue
      extracts. Tissues from the skin, gut, liver and lung were studied, of which
      canine gut appeared to contain the highest levels of tryptase per milligram wet
      weight, which may suggest an important role for this enzyme at this site. This
      assay may prove valuable in assessing the role of mast cells in various disease
      states in the dog.

PMID- 7502486
TI  - Presentation of soluble and bacterial antigens by milk-derived cells to unprimed
      bovine T cells in vitro.
AB  - The ability of cells isolated from bovine milk and peripheral blood to present
      soluble protein and particulate bacterial antigens to peripheral blood T
      lymphocytes was compared using a culture system which consistently supports
      antigen-specific, primary, proliferative responses. The present study shows that
      cells from blood and from milk can present antigen to unprimed T cells. Major
      histocompatibility complex class II restriction of the responses was demonstrated
      by abrogation of proliferation by the addition of anti-bovine class II monoclonal
      antibody to cultures. Although cells derived from blood or milk were shown to be
      capable of presenting antigen to T cells, differences in optimal culture
      conditions and kinetics of the resulting response were observed.

PMID- 7502485
TI  - Interferon induction in peripheral blood mononuclear leukocytes of man and farm
      animals by poxvirus vector candidates and some poxvirus constructs.
AB  - Prototypes of three poxvirus genera--orthopoxvirus (OPV), parapoxvirus (PPV),
      avipoxvirus (APV)--and Newcastle disease virus (NDV) as a control, as well as
      three recombinant OPV strains and one recombinant APV strain, were incubated in
      vitro with peripheral blood mononuclear leukocytes (PBML) of man, sheep and
      swine. Antiviral activity was determined in PBML culture supernatants at
      different time intervals after virus cell interaction using a cytopathic effect
      inhibition bioassay. Additionally, supernatants derived from human PBML were
      screened for interferons (IFN) alpha and gamma as well as for tumor necrosis
      factor by enzyme-linked immunosorbent assay. IFN titers reached a maximum 24 h
      after PBML stimulation at a multiplicity of infection (MOI) greater than 1. IFN
      alpha/beta was found to be responsible for the antiviral effect. Using a MOI > or
      = 1 the highly attenuated strain MVA was the only representant of vaccinia virus
      (VV) that induced significant amounts of IFN also as a lacZ recombinant.
      Replicable virus from five well-known VV strains as well as the Chinese VV strain
      Tien Tan (VVTT) as a recombinant vaccine failed to induce leukocyte IFN.
      Inactivated VV strain Elstree and the recombinant TT strain induced high titers
      of leukocyte IFN. Supernatants derived from human, porcine and ovine PBML
      stimulated with replicable PPV, native VV MVA and MVA lacZ recombinant or native
      APV and APV lacZ recombinant virus regularly contained IFN alpha. In contrast to
      NDV, neither specific antisera nor monoclonal antibodies were able to block the
      INF induction by VV and PPV.

PMID- 7502487
TI  - Isotype-specific antibody responses in sera and mucosal secretions of calves
      experimentally infected with bovine herpesvirus 1.
AB  - Enzyme-linked immunosorbent assays (ELISAs) were developed for studying the
      kinetics of isotype-specific antibody responses in sera, nasal, ocular and
      genital secretions of calves infected with bovine herpesvirus 1 (BHV1). The BHV1
      specific IgM and IgA antibodies were measured in antibody capture assays, and the
      IgG1 and IgG2 antibodies in indirect double antibody sandwich assays. The ELISAs
      were shown to be isotype-specific, sensitive and reproducible. Antibodies of all
      isotypes were able to neutralise the virus in vitro. Calves were infected
      intranasally with one of seven BHV1 field strains. Nine to 13 days after
      infection BHV1-specific antibodies of the IgM isotype appeared in serum, nasal
      and ocular secretions and these were detectable until four weeks after infection.
      The first IgA antibodies were detected a few days later than the IgM antibodies.
      In serum the IgA antibodies were no longer detectable after 3 weeks, but these
      did persist for prolonged periods in mucosal secretions. The calves developed a
      uniform IgG1 response from 13 days after infection, but the IgG2 response was
      quite variable; both persisted until the end of the experiment. No antibody
      responses were detected in genital secretions. There were no marked differences
      in isotype responses between calves infected with different strains of BHV1.

PMID- 7502488
TI  - Improved competitive enzyme immunoassay for the diagnosis of bovine brucellosis.
AB  - A modification of the competitive enzyme-linked immunosorbent assay (C-ELISA) for
      differentiating the antibody response of cattle vaccinated with Brucella abortus
      strain 19 and B. abortus infected cattle is described. This assay utilizes
      lipopolysaccharide as the antigen, immobilized on a polystyrene matrix, and a
      monoclonal antibody (M84) with specificity for an epitope of the O
      polysaccharide. A goat anti-mouse IgG antibody-enzyme conjugate is used for
      detection. The specificity of the modified assay was 99.7% when 1446 sera from
      brucellosis free herds were tested and it correctly identified 636 sera from B.
      abortus infected cattle as positive, using a cut-off of 30% inhibition, for a
      sensitivity estimate of 100%. No reactions were noted among 261 sera from
      vaccinated cattle. However, in testing 1147 sera that gave positive reactions in
      the buffered plate antigen test, the indirect ELISA, the complement fixation test
      or a combination of these tests from the serum bank, 31 gave positive reactions.
      Twenty-seven of the 31 sera originated from recently vaccinated cattle. The
      overall specificity for sera from vaccinated cattle was 97.3%. Because of the
      sensitivity and specificity of this procedure and its ease of performance, it
      would be a reasonable alternative as a single assay for serological diagnosis of
      brucellosis.

PMID- 7502489
TI  - Optimal conditions for measurement of blastogenic responses of chickens to
      concanavalin A in whole blood assays.
AB  - One-day-old chicks (Cobb 500) were raised in wire cages in clean isolated
      conditions and fed on a non-medicated diet. Heparinised peripheral blood samples
      were taken from the cutanea ulnaris (wing) vein. The effect of various parameters
      including concentration of concanavalin A (Con A), dilution of blood in medium,
      volume of blood dilution per culture, type of media, percentage of serum,
      incubation period, concentration of thymidine, pulse-labelling period, and age of
      chickens on the blastogenic response of chickens to Con A was evaluated. The
      results showed that despite a certain degree of individual variation among
      responses, the highest response was to 0.4 microgram Con A per culture at a blood
      dilution of 1/50 in serum-free RPMI 1640 during incubation for 90 h at 40 degrees
      C in a humidified atmosphere containing 5% CO2. Cultures were pulsed with 0.2
      microCi thymidine per culture for 18 h prior to harvesting. The stimulation
      response of chicken whole blood lymphocytes of chickens to Con A was prominent
      from 3 weeks of age onwards and the response measured in chickens 3 weeks of age
      was slightly higher than that of subsequent weeks. The possible applications of
      this technique in studying the pathogenesis of avian diseases and for
      quantitative assessment of circulating T cells of chickens are discussed.

PMID- 7502490
TI  - Selective expression of major histocompatibility complex (MHC) antigens and
      modulation of T-cell differentiation in chickens with increased MHC-chromosome
      dosages.
AB  - Increased dosage of genes belonging to the immunoglobulin superfamily may be
      responsible for some of the less noticeable but targeted phenotypic disturbances
      seen in trisomy conditions of humans and animals. We used an avian aneuploidy
      model to study the specific effects of extra major histocompatibility complex
      (MHC)-microchromosome dosage on the progression of thymocyte differentiation
      through a broad period of embryonic and neonatal development. The particular goal
      in the present investigation was to determine whether a reduction in the number
      of thymocytes, previously observed in the developing thymus of MHC aneuploids, is
      accompanied by particular alterations in thymocyte differentiation. We
      hypothesized that the subpopulation structure and/or developmental pattern for
      thymocyte differentiation are characteristically perturbed (delayed or modified)
      by increased MHC-chromosome dosage in cells. The regulation of MHC surface
      antigen expression in aneuploid thymocytes was also studied to detect dosage
      dependent expression for one and possibly more sub-regions (class I, II, IV) of
      the avian MHC. Surface densities of MHC class I antigens on thymocytes were
      increased significantly at all ages studied, for example by 15% and 45% in
      trisomics and tetrasomics, respectively at 22 days post-hatching. The surface
      density of CT1 antigen, a thymocyte-specific marker, was also increased in a
      dosage-dependent manner, but only in juveniles. Increases in the proportion of
      alpha beta 1, TCR+ and CD3+ thymocytes were observed in juveniles, with no
      alterations in other TCR-expressing thymocytes. No major alterations in CD4 and
      CD8 thymocyte populations were observed. These results demonstrate a targeted
      effect of extra MHC-chromosome dosage towards enhanced class I and CT1, and not
      class II or IV, expression. The increased MHC-microchromosome dosage appears to
      influence primarily immature thymocytes expressing alpha beta 1 TCR and CD3.

PMID- 7502491
TI  - Monoclonal antibodies for the measurement of class-specific antibody responses in
      the green turtle, Chelonia mydas.
AB  - Monoclonal antibodies (Mabs) were developed against the known immunoglobulin
      classes of the green turtle, Chelonia mydas. Plasma protein fractions enriched
      for 5.7S IgY, 7S IgY, and IgM turtle immunoglobulins were used to immunize Balb/c
      mice for hybridoma production and for hybridoma screening. Fifteen hybridomas
      produced Mabs with specificity for turtle immunoglobulins and for affinity
      purified dinitrophenol (DNP) specific turtle antibodies. Three Mabs specific for
      either turtle 5.7S IgY heavy chain (HL814), 7S IgY heavy chain (HL857), or IgM
      heavy chain (HL846) were purified and used in an enzyme-linked immunosorbent
      assay (ELISA) to measure antibody responses in two turtles immunized with 2,4
      dinitrophenylated bovine serum albumin (DNP-BSA) over a 10 month period. In both
      turtles the 7S IgY antibody response developed within 5 weeks of the first
      inoculation and remained high over the following 9 months. The 5.7S IgY antibody
      response was detected in one turtle at 3-4 months and in the other at 8 months,
      and reached high levels in both individuals by 10 months. The IgM responses were
      difficult to interpret. One turtle had pre-inoculation anti-DNP IgM antibody in
      its plasma and the other developed only a weak, transient response at about 4
      months. The class-specific antibody activity in immune turtle plasma could be
      strongly inhibited by soluble DNP or by rabbit anti-DNP specific antiserum,
      showing that these antibody responses were directed predominantly to the DNP
      hapten on the DNP-BSA antigen. Antibody responses to the BSA carrier could not be
      detected in either turtle over the course of the immunization. Mab HL814,
      specific for an epitope on the 5.7S green turtle immunoglobulin heavy chain, will
      be useful for characterizing the molecular relationships of 5.7S, 7S and IgM
      heavy chains and the role of 5.7S antibody in humoral immunity in this species.
      All anti-turtle Ig Mabs were screened against the plasma globulins of Loggerhead
      (Caretta caretta), Olive Ridley (Lepidochelys olivacea), Kemp's Ridley
      (Lepidochelys kempi), Hawksbill (Eretmochelys imbricata), and Leatherback
      (Dermochelys coriacea). While the Mabs specific for IgM and 5.7S IgY reacted only
      with the green turtle, two Mabs specific for light chain reacted with all species
      except the leatherback, and nine mabs specific for 7S IgY heavy chain reacted
      with all five species. Thus, these Mabs may be useful for immunodiagnostic
      applications in these endangered species as well.

PMID- 7502493
TI  - Immunocytochemical analysis of a monoclonal antibody specific for rainbow trout
      (Oncorhynchus mykiss) granulocytes and thrombocytes.
AB  - A monoclonal antibody against rainbow trout peripheral blood leucocytes was
      selected for its lack of reactivity with rainbow trout immunoglobulin. Its
      reactivity with leucocytes from peripheral blood, head kidney and spleen was
      analysed by flow cytometry and electron microscopy, and compared with that of
      monoclonal antibodies directed against rainbow trout immunoglobulin, which
      reacted with B cells, B lymphoblasts and plasma cells. The antibody reacted with
      5-20% of the peripheral blood leucocytes, 8-9% of head kidney leucocytes and 5-7%
      of spleen leucocytes. Electron microscopical immunocytochemistry revealed that
      the antibody reacted strongly with granulocytes and weakly with thrombocytes, and
      not with erythrocytes, lymphocytes, monocytes or macrophages. The antibody has
      possible applications in the identification and isolation of rainbow trout
      leucocytes, either alone or in combination with other monoclonal antibodies.

PMID- 7502492
TI  - Studies on the haemolytic complement of the dromedary camel (Camelus
      dromedarius). I. Classical pathway haemolytic activity in serum.
AB  - Classical pathway haemolytic complement (CPHC) of the dromedary was assayed under
      standardised conditions. A total of 14 indicator systems of red blood cells (RBC)
      and haemolysins were investigated. Highest CH50 titre was obtained with rabbit
      RBC sensitised with goat haemolysin. Among the factors investigated were: ionic
      strength, Mg2+, Ca2+, ethylenediaminetetraacetic acid (EDTA) concentration, pH,
      incubation time and temperature. The standard system of titrating the HC levels
      consisted of rabbit RBC sensitised with goat haemolysin, sucrose veronal buffer
      (SVBS) pH 7.4, ionic strength 0.14 M and Ca2+ and Mg2+ concentrations of 4.0 x
      10(-4) M and 1 x 10(-3) M, respectively. Incubation at 37 degrees C for 120 min
      gave the highest HC activity. Using these standardised conditions HC levels were
      determined in 79 camels aged between 3 months and 15 years. Highest mean HC value
      of 873 +/- 26.6 CH50 units ml-1 were recorded in the age group of 1-5 year old
      camels and the lowest mean HC value of 598 +/- 120.8 CH50 units ml-1 in the age
      group of 10-15 year old camels. Adult males in the age group 5-10 years had
      significantly higher mean HC levels than their female counterparts (P < 0.0001).

PMID- 7502494
TI  - Uterine carcinomas in mother cats after intrafetal inoculation of allogeneic
      tumor cells (K248 C and P).
AB  - Three out of 13 queens that had undergone injection of tumor cells from an
      allogeneic feline mammary carcinoma cell line through the wall of the pregnant
      uterus developed a carcinoma of the uterus. The possible role of immune tolerance
      associated with pregnancy and/or major histocompatibility complex (MHC)
      compatibility is discussed.

PMID- 7502495
TI  - A comparison of colon cancer cases at the Charleston Area Medical Center with the
      National Cancer Data Base report.
AB  - This article reviews the pattern of care and outcome of colon cancer cases seen
      at Charleston Area Medical Center (CAMC) between 1985 and 1991, and compares
      these statistics to the most current National Cancer Data Bank (NCDB) study.
      CAMC's statistics paralleled those of the NCDB study in several ways including
      the fact that both studies indicated that there appeared to be stability in the
      age and gender distribution of colon cancer between 1985 and 1991, and there was
      a continued trend of proximal migration of colon cancers. Both the CAMC and NCDB
      studies also indicated that AJCC staging was used increasingly as the standard of
      cancer diagnosis, and that multimodal therapy (e.g., chemotherapy) was
      increasingly available to patients at greatest risk for recurrence after surgery
      (stage III patients). However, the CAMC study indicated that compared to the
      NCDB, there was a greater incidence of colon cancer in females, and that a
      greater percentage of stage III patients received adjuvant therapy in 1990 (35.9%
      and 70% in the NCDB and CAMC studies respectively).

PMID- 7502496
TI  - Transvenous implantation of cardioverter defibrillators in the Electrophysiology
      Laboratory at CAMC.
AB  - Since 1989, 78 patients have had Implantable Cardioverter Defibrillator (ICD)
      systems implanted in the Electrophysiology Laboratory (EPS) at the Charleston
      Area Medical Center. Between June 1993 and December 1994, 28 patients (21 males,
      7 females) had new transvenous ICD systems successfully implanted in the
      Electrophysiology Laboratory. Coronary artery disease was present in 22 patients
      (76%). The mean left ventricular ejection fraction measured 28 percent (range 19%
      45%), and the mean follow-up was 159 +/- 112 days (5.3 months). Twelve patients
      (43%) experienced shock, with an average of three per patient. The implantation
      of transvenous ICD systems in an electrophysiology laboratory is feasible,
      efficacious, safe, and associated with rapid patient recovery. With advances in
      technology, the procedure is becoming more comparable to a pacemaker
      implantation.

PMID- 7502497
TI  - Prospective comparison of laparoscopic and open cholecystectomy in a community
      hospital.
AB  - Despite reports questioning its relative safety, laparoscopic cholecystectomy has
      gained rapid acceptance on the surgical scene in the past few years due to its
      perceived, but unproven advantages related to patient recovery and health care
      costs. This article describes a study conducted at the Charleston Area Medical
      Center in order to prospectively evaluate the comparative outcomes and expenses
      for 17 patients undergoing open cholecystectomies by a single surgeon using
      techniques of vigorous perioperative care, as well as 30 patients undergoing
      laparoscopic cholecystectomies by a single experienced laparoscopist. Results
      indicated that although patients undergoing laparoscopic cholecystectomy had a
      slightly shorter average length of hospitalization and used fewer postoperative
      analgesics, the average recovery time and hospital costs for the two procedures
      were similar.

PMID- 7502498
TI  - The effect of granulocyte colony stimulating factor in patients with leukopenia
      due to sepsis.
AB  - The use of granulocyte stimulating factor (G-CSF) (Neupogen, Amgen Inc., Thousand
      Oaks, Calif.) has become acceptable for treating both primary and acquired
      leukopenia. Leukopenia associated with infection is an ominous sign of
      overwhelming sepsis. In this article, we present two cases of infection that were
      related to leukopenia which were successfully treated with G-CSF.

PMID- 7502499
TI  - Medical care compliance.

PMID- 7502500
TI  - Near infrared spectroscopy: methodological principles and clinical application in
      preterm infants.
AB  - Neonatal encephalopathy, plausibly related to hypoxia and ischaemia, remains one
      of the main problems in perinatal medicine. Efforts are necessary to find new non
      invasive methods for assessing brain oxygenation. Near infrared spectroscopy
      (NIRS) provides information on the concentrations of the oxygenated and
      deoxygenated forms of haemoglobin, as well as of the redox state of cytochrome
      aa3. Different important variables such as cerebral blood volume and flow, and
      the responses of these to changes in pCO2, can be derived through haemoglobin
      measurement. Changes in cytochrome aa3 may provide immediate information on
      intracellular oxygen utilization. Various studies have shown the feasibility of
      NIRS in preterm infants. Methodological and technical problems of this method are
      discussed.

PMID- 7502501
TI  - [Population study in West Austria using DNA single locus probes].
AB  - Allele frequency distribution of the single-locus system YNH 24 (n = 302), G3 (n
      = 251), MS 43A (n = 333), and MS 31 (n = 333) was determined in Western Austria.
      After digestion with Hinf I, electrophoresis and Southern blotting, the genomic
      DNA was hybridised with the probes YNH 24, G3, MS 43A, and MS 31. Blood samples
      were taken from 333 unrelated caucasians living in the area of Innsbruck, Tyrol,
      Austria. The fragment distribution was calculated for each of the 4 single-locus
      systems. A single fragment pattern, indicating homozygosity, was shown in 9.93%
      with YNH 24, 12.45% with G3, 9.61% with MS 43A, and 7.21% with MS 31; the
      corresponding heterozygosity rates were 90.07%, 87.55%, 90.39%, and 92.79%,
      respectively. Our data are compared with those from England [18], Germany [3],
      Greenland [7], and Denmark [14]. Discrimination indices (Table 2) were calculated
      and statistical parameters (Table 3) presented.

PMID- 7502502
TI  - Dietary vitamin D intake in patients with Crohn's disease.
AB  - In search for the reasons of vitamin D deficiency in Crohn's disease (CD),
      dietary records were evaluated over 7 days in 30 uninformed out-patients with CD
      (but no current flare-up) by the help of food tables and compared with those of
      30 age- and sex-matched healthy controls. The study was undertaken in December.
      The nutritional status (height-weight index) was similar in both groups. The
      dietary vitamin D intake was as low in patient with CD (1.0 microgram/d; 0.5-1.3)
      as in the controls (1.1; 0.4-1.6) whereas the recommended daily intake is 5
      micrograms/d. Vitamin D intake correlated with serum 25-hydroxyvitamin D (25-OHD)
      levels in patients with low 25-OHD levels (tau = 0.45, p = 0.04). Bone mineral
      content (BMC)-measured by single photon absorptiometry on the radius- was
      decreased in 9 patients (31%) with CD. Patients with CD tended to have a lower
      sun exposure in summer (p = 0.10), which also correlated with BMC (p = 0.03).
      Hence, a specific diet with a high vitamin D content, or vitamin D
      supplementation is recommended in patients with CD to overcome the negative
      effects of low sun exposure on bone mineral density.

PMID- 7502503
TI  - [Initial experiences with hip joint arthroscopy. Report based on 2 cases].
AB  - In order to put the value of hip joint arthroscopy into correct perspective we
      report that among over 500 operations undertaken in the hip region annually-cases
      of readjustment osteotomy, osteosynthetic and prosthetic surgery-at the Graz
      Hospital for Accident Surgery there is about one case of hip joint osteotomy.
      Arthroscopy of the hip joint is a technically sophisticated examination which is
      only performed for the strictest indications. After reviewing data from the
      relevant literature we present two cases and discuss the indications for and
      technique of this operation.

PMID- 7502504
TI  - Rounded atelectasis associated with silicosis.
AB  - Two cases of autopsy-proven, silicosis-associated rounded atelectasis (SARA) are
      reported. Clinicopathologically, SARA shows a combination of rounded atelectasis
      and the typical features of silicosis. Pathologically, SARA is characterised by
      the presence of numerous silicotic nodules deposited throughout the atelectatic
      lung tissue, which otherwise shows the ordinary features of rounded atelectasis.
      SARA may contribute to the development of massive fibrosis in silicotic lungs.

PMID- 7502505
TI  - [Anti-Jo-1-positive polymyositis with interstitial alveolitis and pericardial
      effusion. Overview of 3 years treatment].
AB  - We describe the case of a 53-year-old woman who developed polymyositis with
      extramuscular complications: interstitional lung fibrosis, pericarditis and a
      pericardial effusion, polyarthritis, Raynaud's syndrome, carpal tunnel syndrome,
      sclerodactylia and positive anti-Jo-1-antibodies. We treated her for 3 years.
      Pericarditis and pericardial effusion with a fibrosing lung alveolitis were the
      first clinical manifestations of positive Jo-1-syndrome. We stress the patient's
      serious cardiac disease accompanied by pericardial effusion, which has seldom
      been described in specialist articles. Steroid treatment induced remission of the
      disease, but the Jo-1-antibodies did not disappear from the patient's serum.

PMID- 7502506
TI  - [Guidelines for managing HBV, HCV, and HIV infections in obstetrics].

PMID- 7502507
TI  - [Intra-amniotic infection, cytokines and premature labor].
AB  - This paper reviews the mechanisms leading to the commencement of labor in the
      presence of intrauterine infection. It is postulated that induction of preterm
      contractions represents an escape mechanism of the fetus from a hostile
      environment. Bacterial toxins provoke an immunological response (macrophages) of
      the fetomaternal compartment. Liberation of cytokines (IL-1, IL-6, IL-8)
      stimulates prostanoid synthesis in the decidua and amnion, as well as migration
      of granulocytes into the cervix. Additional still unknown factors may determine
      whether this process leads to cervical dilatation, effacement and finally preterm
      delivery. The role is discussed of other cytokines, i.e., colony-stimulating
      factors, transforming growth factor beta, and interleukin receptor antagonists as
      potential, clinically useful tocolytics in this labile equilibrium.

PMID- 7502508
TI  - [Pregnancy in patients with congenital heart defect].
AB  - A process of adaptation of the cardiovascular system occurs during pregnancy,
      entailing physiologic changes. In women with congenital heart disease these
      changes lay a great burden on the cardiovascular system. Therefore there is an
      increased risk for mother and fetus, depending on the form of congenital heart
      disease, preceding operations and the grade of maternal hypoxemia. Overall, the
      maternal mortality is low, but in certain forms of congenital heart disease the
      mortality rate can rise to 50%. Infective endocarditis and anticoagulation
      therapy represent further problems for mother and fetus. It is the duty of the
      cardiologist, general practitioner and obstetrician to counsel the patient before
      conception on potential complications and risks of pregnancy, expected physical
      deterioration of the mother, as well as possible malformations of the child,
      including the recurrence risk of congenital heart disease. If pregnancy is
      contraindicated because of the severity of the heart disease, the patient has to
      be advised about reliable contraceptive methods tailored to her individual needs
      and their risks, including possible endocarditis, bleeding under anticoagulation
      therapy, thrombosis, toxic shock syndrome etc.

PMID- 7502509
TI  - [Granisetron, a antiemetic for treatment of cytostatic drug-induced vomiting:
      results of a practice-oriented study].
AB  - The present multicentre Austrian investigation of the prophylactic intravenous
      administration of granisetron, a serotonin antagonist, routinely for control of
      cytostatic-induced nausea and emesis was carried out in 102 patients with cancer
      of various types undergoing different emetogenic cytostatic regimens (232 cycles
      of chemotherapy). A major therapeutic response, i.e. maximally one vomit over the
      first 24 hours, was achieved in 78-90% of patients undergoing a single or
      multiple day regimen of chemotherapy. Delayed emesis, experienced between day 1
      and day 4 after chemotherapy, was observed in < 5% of the patients. However,
      particularly in single day regimens 25% of the patients showed only a moderate
      response to granisetron in suppressing delayed emesis. Tachyphylaxis to
      granisetron therapy was not observed in the first 3 consecutive cycles of
      chemotherapy. The individual global efficacy of emesis control by granisetron
      (day of chemotherapy over all cycles plus the following 7 days) was very good. An
      excellent therapeutic response was seen in 53-55% of all cases. The study also
      demonstrated the economic advantages of granisetron therapy. In the majority of
      patients (88/102) only a single dose of granisetron (3 mg) was required. The
      tolerability was also very good. The main adverse events reported were headache
      (7.8%) and constipation (4.9%).

PMID- 7502511
TI  - [Results of the 3rd Consensus Conference on "Individualized Therapy of
      Hypertension" and brief explanation of individual evaluation].

PMID- 7502510
TI  - [Correlation of skinfold thickness with bone density and estradiol, FSH and
      prolactin level in a sample of 231 women].
AB  - Skin thickness was measured by means of ultrasound and correlated with the
      results of bone densitometry and hormonal parameters. Skin thickness and bone
      density were significantly correlated (p < 0.0001). These results indicated that
      not only bone, but also skin is a hormone-dependent organ, which responds to the
      menopausal decrease in sexual steroids. Hence, skin ultrasound, just like bone
      densitometry, can be useful implemented in the differential diagnostic procedure,
      as well as the therapy of the menopausal syndrome. Additionally, the estrogen
      dependent postmenopausal decrease in collagen tissue can be assessed by
      ultrasound and a successful therapeutic outcome achieved by optimizing the dosage
      of estrogen substitution.

PMID- 7502512
TI  - [Individualized therapy of hypertension. The Austrian Professional Group of
      Clinical Pharmacology].
AB  - The Austrian Working Group on "Individualization of Antihypertensive Therapy"
      (IHT) published guidelines for the treatment of hypertensive patients with
      additional risk factors, diseases and other circumstances leading to a
      modification of the standard therapy. According to the number of prescribeable
      drugs the quantity of different recommendations is difficult to be followed
      without assistance. To support the performance of the guidelines, the Austrian
      Working Group IHT offers instructions (folder) and PC-Software.

PMID- 7502513
TI  - [Interactions between antihypertensive agents of different mechanisms of action].
AB  - The combinations of different antihypertensive agents exerts nearly always a
      pharmacodynamically mediated synergistic effect. Pharmacokinetic interactions on
      the other hand are rare.

PMID- 7502514
TI  - [Hypertension and hemorheology].
AB  - A number of epidemiologic studies have provided evidence for an increased blood
      viscosity in hypertensive patients. Increased viscosity could result either from
      hemoconcentration, thus constituting a secondary phenomenon, or, alternatively,
      result directly from increased intracellular calcium concentrations in
      erythrocytes. The latter would augment the aggregating potential of these
      cellular blood compounds. This currently hypothetic view remains to be
      elucidated. Enhanced viscosity, however, may result in increased peripheral
      resistance and lead to hypertensive complications. The evaluation of
      antihypertensive therapy should therefore take possible effects upon blood
      viscosity into account.

PMID- 7502515
TI  - Non-responders.
AB  - Non-responders are frequently encountered in clinical practice, and different
      strategies have to be considered as well as diagnostic approaches. Nearly 50% of
      all hypertensive patients will require more than one drug to control blood
      pressure. The complexity of high blood pressure is reflected in the different
      responses to antihypertensive agents with varied mode of action. White coat
      hypertension may coexist with sustained hypertension and complicate
      interpretations of blood pressure measurements. Noncompliance is a challenge for
      the doctor, and may be difficult to solve. It depends not only on the patient
      doctor relationship, but also on the patient's perception of own health and the
      side effect profile of the drugs. Patient education is crucial. Secondary
      hypertension should be excluded in truly resistant hypertension. Volume overload
      is frequent in essential hypertension, and volume expansion follows an excessive
      dietary sodium intake. These and other possibilities should be sought for when
      explaining failure to respond to antihypertensive therapy.

PMID- 7502516
TI  - [Patient compliance of hypertensive patients in the physician's practice].
AB  - Compliance of hypertensive patients is primarily estimated in participating
      patients in clinical trials. Although compliance is overestimated by pill
      counting, this technique is most frequently used. 389 Austrian general
      practitioners studied compliance in 945 hypertensives, using the Medication Event
      Monitoring System. The patients were asked to take the ACE-inhibitor Cilacapril
      once a day between 7.00 a.m. and 9.00 a.m. Each package opening was registered by
      a microprocessor located in the cover of the drug vial. In this study it turned
      out that only 1.3% of the patients did open their vials between 7.00 a.m. and
      9.00 a.m. 2 thirds of the patients actually took less than 80% and 36% less than
      half of the prescribed medication. There was no correlation between compliance
      and sex, age, smoking habits, tolerance or duration of hypertension. Even fall in
      blood pressure was the same in compliant and non compliant patients. The
      conclusion is that compliance is bad in a general practitioner setting and
      further more that casual readings as performed in this study are an insufficient
      tool to judge efficacy.

PMID- 7502517
TI  - [What are the therapeutic consequences of evaluating hypertensive patients with
      24-hour blood pressure monitors and blood pressure self-measurement?].
AB  - Arterial hypertension is an important risk factor for excessive cardiovascular
      morbidity and mortality due to its high prevalence of about 20% in the adult
      population. Causal readings, which have been obtained for diagnosis and control
      of treatment in hypertension are of limited value. They are not reproducable due
      to physiologic variability of blood pressure, which causes a rise of blood
      pressure, if a straining situation (e.g. in doctor's office) occurs (white-coat
      hypertension). Furthermore, no correlation between causal readings and signs of
      endorgan-damage (EOD) such as left ventricular hypertrophy (LVH) can be observed.
      Especially the development of LVH comprises an independent risk factor and
      worsens prognosis. Results of ambulatory monitoring and self-measurement of blood
      pressure are reproducable and show an excellent correlation to EOD. Both methods
      are able to exclude white-coat-hypertension. Furthermore, ambulatory blood
      pressure monitoring allows to obtain blood pressure values during sleep, which
      may give further information concerning secondary hypertension, EOD and
      prognosis. Self measurement of blood pressure reinforces compliance of the
      patient and gives the possibility of self-titration and long-term control of
      antihypertensive drug treatment. The non-consensus concerning normal values is
      one limitation of both methods, but the cut-off level of office blood pressure
      recordings appears arbitrary, too. For optimal concomittance of hypertensives
      both methods have to reach more importance for diagnosis, evaluation of prognosis
      as well as treatment control.

PMID- 7502519
TI  - The pathways regulating acid secretion: the view from the isolated cell.
AB  - Although many aspects of the regulation of acid secretion at the cellular level
      among different species remains controversial, certain concepts have emerged that
      span the differences between species, model systems and investigators. The
      paracrine, endocrine, neural and autocrine pathways mediate acid secretion by
      acting both directly on the parietal cell and indirectly via modulation of
      mucosal paracrine cell function. Studies with cells isolated from the acid
      secreting canine oxyntic mucosa indicate that gastrin and cholinergic receptors
      are present on parietal cells, somatostatin cells, and the histamine
      enterochromaffin-like cell (ECL). Subtypes of these receptors are clearly
      important; the gastrin receptor on the ECL cell and parietal cell are "B" type
      CCK/gastrin receptors, whereas the receptor on the somatostatin cell is an A type
      CCK receptor. From the vantage point of studies in the canine oxyntic mucosa, the
      challenge is no longer to determine whether parietal, histamine or somatostatin
      cells have gastrin or muscarinic receptors but to establish the physiologic
      relevance of the specific actions (secretory, trophic or differentiative) of
      these receptor subtypes. Furthermore, the mechanisms integrating these paracrine,
      exocrine and neural elements require elucidation.

PMID- 7502518
TI  - [Evaluation of the antihypertensive drugs carvedilol, doxazosin and moxonidine].
AB  - Carvedilol, Doxazosin and Moxonidine are rather novel antihypertensive
      substances, which belong to "beta-adrenoceptor-antagonists", "alpha 1
      adrenoceptor-antagonists" and "antisympathotonic substances" respectively.
      Besides its nonselective beta-adrenoceptor-antagonistic activity, Carvedilol
      possesses smooth vascular relaxant and alpha 1-antagonistic effects. Since beta
      adrenoceptor-antagonists are, together with diuretics, the only antihypertensives
      for which a decrease in mortality rate has been verified, Carvedilol by its site
      of action also belongs to that antihypertensive family. Many investigations have
      shown that the alpha 1-adrenoceptor-antagonist Doxazosin is as effective in blood
      pressure lowering as other antihypertensive substances and has only a few side
      effects. With respect to the hypotensive action, the antisympathotonic substance
      Moxonidine is as effective as Clonidine is, but side effects occur 50% less in
      comparison to Clonidine. The 3 substances enlarge the antihypertensive therapy.
      However, mortality studies are required to test their comparability to the other
      first line antihypertensive substances.

PMID- 7502520
TI  - H3-receptor regulation of vascular gastrin and somatostatin releases by the
      isolated rat stomach.
AB  - We have studied the effects of the H3-receptor agonist (R) alpha-methylhistamine
      [(R) alpha-MeHA] and the H3-receptor antagonist thioperamide (Thiop) on basal-
      and carbachol-stimulated vascular gastrin release (GR) and somatostatin release
      (SR) by the isolated rat stomach. Carbachol dose-dependently stimulated and
      inhibited GR and SR, respectively. Maximal stimulation of GR (500 +/- 112 percent
      of basal; p < .01), and maximal inhibition of SR (-62 +/- 9 percent under basal;
      p < .01) were obtained with 1 micron carbachol. Neither (R)alpha-MeHA nor Thiop,
      up to 10 microns, affected GR. However, SR was dose-dependently enhanced by Thiop
      (25 +/- 8 percent for 10 microns). Carbachol stimulation of GR was strongly
      inhibited by Thiop (30 +/- 7 percent for 100 nM and 73 +/- 14 percent for 1
      microgram), whereas it was potentiated by (R)alpha-MeHA. Carbachol inhibition of
      SR was reversed by Thiop and (R)alpha-MeHA. However, the reversal effect of
      (R)alpha-MeHA was prevented by the CCKB/gastrin receptor antagonist PD134308.
      These results support H3-receptor regulation of basal and cholinergically
      stimulated GR and SR.

PMID- 7502521
TI  - The biology and physiology of the ECL cell.
AB  - The enterochromaffin-like (ECL) cells, which are the predominant endocrine cell
      type in the acid-producing part of the vertebrate stomach, are characterized by
      numerous, electron-lucent vesicles and few electron-dense granules in the
      cytoplasm. The biological and physiological significance of the ECL cells remains
      poorly understood. They produce and store histamine and pancreastatin and are
      thought to produce an as yet unidentified peptide hormone. The most important
      clue to their function is their willingness to respond to changes in circulating
      gastrin. The present review presents current knowledge of the biology and
      physiology of the rat stomach ECL cells. Examination of serially sectioned ECL
      cells has revealed that the cytoplasmic vesicles almost invariably contain an
      electron-dense core, suggesting that perhaps the distinction between granules and
      vesicles is artificial. We propose a life cycle of the secretory organelles in
      the ECL cells with a progressive development from granules to vesicles. The
      results showed that the gastrin-evoked release of histamine and pancreastatin was
      accompanied by loss of vesicles, and that synthesis of histamine and
      pancreastatin was accelerated by sustained infusion of gastrin, a treatment that
      was associated with renewal of vesicles. The events described are instrumental in
      bringing about a change in the "steady state" or "equilibrium" of the ECL cells,
      from a non-stimulated, resting state to a gastrin-stimulated, active state. This
      change is attained within six to eight hr. The next "steady state" change is that
      from "normal-sized" but active ECL cells to "hypertrophic" ECL cells. The
      increase in cell size is complete after about one week. The gastrin-evoked
      increase in the ECL cell self-replication rate is maximal after about 10 days,
      after which time there is a gradual return back to pre-stimulation values. The
      ECL cell density increases fairly slowly and does not reach maximum (four-fold
      increase) until after 20 weeks hypergastrinemia. The activity of the histamine
      forming enzyme, histidine decarboxylase, is elevated by gastrin and remains
      elevated for as long as the gastrin stimulus is maintained (the longest time
      studied was 20 weeks). The physiological significance of the ECL cells is
      probably related to their capacity to produce and store histamine and an as yet
      unidentified peptide hormone. The ECL cells are thought to be the source of
      histamine necessary for the gastrin-evoked acid response. In addition,
      preliminary evidence suggests that the ECL cells and the anticipated ECL cell
      hormone play a role in bone formation.

PMID- 7502522
TI  - Inflammation, acid and ulcers.
AB  - Chronic active type B gastritis is invariably the result of Helicobacter pylori
      infection and is an important factor in duodenal ulcer disease. The actions of
      mediators produced (a protein factor, a lipid soluble "pore-forming factor" and
      urease) or induced (immune/inflammatory cell mediators) by this bacterium on the
      control of gastric acid secretion are currently being investigated. These studies
      are reviewed in light of our current knowledge of the physiological control of
      gastric acid secretion.

PMID- 7502523
TI  - Vagal regulation of acid secretion and gastrin release.
AB  - The vagus nerve plays a central role in the regulation of gastric acid secretion
      and gastrin release. The current understanding of the mechanisms involved in
      vagal regulation of acid secretion and gastrin release is reviewed. Thyrotropin
      releasing hormone from the medullary raphe nuclei appears to be the central
      excitatory mediator of vagal action in the dorsal motor nucleus. Vagal
      stimulation of the parietal cell occurs through M3 cholinergic receptors and via
      the release of histamine and gastrin from enterochromaffin-like cells and G
      cells, respectively. Somatostatin exerts a tonic basal inhibition of both the
      parietal cell and the G-cell. Vagal stimulation suppresses somatostatin release
      from delta cells, thereby "disinhibiting" these cells.

PMID- 7502524
TI  - Therapeutic applications of vagotomy.
AB  - The treatment of the peptic ulcer disease involves several options. The present
      discussion deals with the long-term management with emphasis on the application
      of vagotomy. Eradication of Helicobacter pylori is the treatment of choice in
      ordinary peptic ulcer patients. Exceptions are non-steroidal, anti-inflammatory
      drug-induced ulcers and the Zollinger-Ellison syndrome. Failures to eradicate H.
      pylori in old or unfit duodenal ulcer patients and most gastric ulcer patients
      will lead to intermittent antisecretory treatment or continuous maintenance
      treatment. Maintenance treatment will usually mean lifelong treatment, and
      optimal results are probably obtained with a full-dose antisecretory regime.
      Failures to eradicate H. pylori in young and fit duodenal ulcer patients is the
      group of patients to whom proximal gastric vagotomy can still be recommended as
      an elective surgical procedure. The proximal gastric vagotomy should preferably
      be performed with the laparoscopic technique. Evidence is presented that
      completeness of vagotomy is of clinical importance. The completeness of vagotomy
      can be tested and defined.

PMID- 7502525
TI  - Minimal access surgery--the renaissance of gastric surgery?
AB  - Peptic ulcer surgery has been revitalized by the introduction of minimal access
      techniques for surgery of chronic and perforated peptic ulcer. A wide range of
      vagotomies, including truncal vagotomy, anterior lesser curve seromyotomy with
      posterior truncal vagotomy and proximal gastric vagotomy, have been performed
      laparoscopically. Short-term (two-24 month) follow-up of laparoscopic anterior
      seromyotomy with posterior truncal vagotomy cases has been promising, but long
      term follow-up is required to confirm these early good results. Laparoscopic
      repair of perforated peptic ulcers has also been described. Initial reports of
      laparoscopic gastrojejunostomy and Billroth II partial gastrectomy have also
      appeared. These procedures are technically very demanding and are currently being
      performed in only a few "centers of excellence" around the world. Cost-benefit
      analyses of medical treatment with proton-pump inhibitors versus laparoscopic
      vagotomy are necessary to determine which form of treatment is more economical in
      the long run. Criteria for patient selection need to be defined and substantiated
      by audit of outcome.

PMID- 7502526
TI  - Endoscopic management of ulcer disease.
AB  - Endoscopy has revolutionized the management of digestive diseases in general and
      ulcer disease in particular. It allows the physician to view the pathologic
      process directly, and with biopsy and cytology techniques, to obtain histological
      samples. Endoscopy helped to usher in the field of minimally invasive therapy and
      endoscopic treatment of bleeding ulcers and is now a standard form of treatment.
      This overview is divided into three parts: first, the current diagnostic and
      therapeutic endoscopic management of ulcer disease will be addressed; second,
      some of the current work that should have future applications in the same area
      will be discussed. Finally, some conceptual ideals that look further beyond
      future applications will be addressed.

PMID- 7502527
TI  - Dragstedt, gastric acid and duodenal ulcer.
AB  - Dragstedt believed that basal hypersecretion of gastric acid was the root cause
      of duodenal ulcer, that the hypersecretion was due to an increased vagal
      stimulation, and that vagotomy would therefore cure duodenal ulcer. He introduced
      vagotomy and demonstrated that the operation was successful in curing most
      patients of their duodenal ulcers. This article reviews how further research in
      the succeeding half century has demonstrated that it is the effect of vagotomy on
      stimulated, rather than upon basal secretion that cures duodenal ulcer and that
      the apparent basal hypersecretion of patients with duodenal ulcer is due to an
      increased parietal cell mass. The article points out that there is no convincing
      explanation as yet of the mechanism whereby vagotomy reduces histamine-stimulated
      gastric secretion.

PMID- 7502528
TI  - The consequences of hypergastrinemia.
AB  - The only gastrin-dependent gastric endocrine cells are the fundic ECL cells.
      Excessive hypergastrinemia stimulates ECL cell proliferation in animals and man.
      The growth of other gastric endocrine cells is regulated by the gastric pH.
      Hypergastrinemia in man results in diffuse and linear hyperplasia of the ECL
      cells, while micronodular hyperplasia is correlated to the grade of corpus
      gastritis. ECL cell dysplasia and gastric carcinoids in man have been observed
      only in patients with gastrinoma as part of the MEN I syndrome and with
      pernicious anemia. Gastrin dependence of GI adenocarcinoma has not been
      established. Experimental findings may be explained by the presence of gastrin
      receptors and the role of gastrin as an autocrine growth factor. Epidemiological
      data do not support gastrin dependence of carcinoma of the stomach, the pancreas
      and the colon.

PMID- 7502529
TI  - Zollinger-Ellison syndrome: past, present and future controversies.
AB  - It is fitting that the Zollinger-Ellison syndrome (ZES) be included in the Lester
      Dragstedt Symposium because Dr. Dragstedt had a long-time interest in this
      disease, having been one of the five discussants of the original article and
      subsequently reporting with Dr. Oberhelman on nine cases. The approach to therapy
      of ZES has been controversial from the beginning, and a number of controversies
      remain. In this article, four different controversies are analyzed from the
      prospective of the past (Zollinger-Dragstedt era, 1955-1980), present and what
      may happen in the future in light of recent results. Specifically analyzed are:
      1) the role of gastric surgery in the management; 2) whether gastrinoma removal
      without aggressive resection in patients with ZES without MEN-I is the preferred
      surgical therapy; 3) whether patients with MEN-I should undergo routine surgical
      exploration; and 4) whether most gastrinomas will be localized preoperatively. An
      analysis of recent advances suggests there may be marked changes in the future
      from our current and our past approaches.

PMID- 7502530
TI  - Somatostatin receptors on neuroendocrine tumors--a way to intraoperative
      diagnosis and localization.
AB  - Intraoperative radionuclide detection using 111In-DTPA-D-Phe1-octreotide was
      evaluated in five patients with midgut carcinoids and in three patients with
      recurrent medullary thyroid carcinoma. Three different time intervals (24, 48 and
      120 hr) from injection of the radiopharmaceutical to surgery were used. At
      surgery, suspect tumors were measured by probe in situ and ex vivo after
      excision. All tissue specimens and blood samples withdrawn during surgery were
      measured for 111In activity, and tissue/blood activity concentration ratios were
      calculated. In situ measurements were valuable especially in neck surgery, where
      the probe was helpful not only in localization of tumors but also in the control
      of tumor clearance. Ex vivo measurements were helpful in diagnosing tumor tissue.
      All five patients with midgut carcinoids were somatostatin receptor-positive,
      while only three out of seven patients with medullary thyroid carcinoma were
      receptor-positive. The tissue/blood activity concentration ratios and probe
      measurement ratios were in general higher in patients with midgut carcinoid than
      in patients with medullary thyroid carcinoma. Of particular interest were the
      high tissue/blood concentration ratios in all receptor-positive patients at all
      time intervals studied. This fact suggests a potential role for radiolabelled
      octreotide in radiotherapy of these tumor types.

PMID- 7502531
TI  - Medical management of esophageal reflux.
AB  - Gastroesophageal reflux of varying severity is a common disorder for which
      medical attention is sought at all levels, from pharmacists to specialist
      physicians and surgeons. This brief overview represents my current understanding
      of reflux, its effects on the esophagus and my personal approach to treatment of
      these disorders. Of necessity, because the literature is so extensive (a Medline
      search on reflux from 1966 to 1993 yielded over 1500 papers.), I have relied in
      places on the extensive review by Marks and Richter [1]. My paper emphasizes the
      evaluation and treatment of patients with symptomatic reflux, esophagitis and its
      complications. It describes why it is important to grade the disorders so that
      the treatment used is appropriate to the severity of the disease. The more severe
      the disease, the more specific the diagnostic information needed and the more
      exacting the treatment. Various treatments and outcomes of therapy are discussed,
      and a role for surgery is defined. The essence of effective medical treatment of
      esophagitis is to reduce acidity of the refluxate to a level outside the optimum
      proteolytic pH range of pepsin, i.e. greater than pH 3.5.

PMID- 7502533
TI  - Lester Dragstedt Centenary Symposium. New Haven, Connecticut, October 1, 1993.
      Proceedings.

PMID- 7502532
TI  - The knife or the pill in the long-term treatment of gastroesophageal reflux
      disease?
AB  - Gastroesophageal reflux disease (GERD) is a common condition, and it is now
      generally recognized that modern medical therapy allows the physician to both
      heal the esophagitis and relieve the patients from troublesome symptoms such as
      heartburn, acid regurgitation and disabling chest pain. In addition, long-term
      therapy with potent acid inhibitory drugs can maintain these patients in clinical
      remission. The indications for antireflux surgery and long-term medical therapy
      have developed and changed with time but are today essentially similar, and in
      fact, it can be hypothesized that the outcome of a short-term "therapeutic
      trials" with the proton pump inhibitor would be a useful clinical tool, not only
      as a diagnostic test for the disease but also in the selection process before
      referring the patient to antireflux surgery. Antireflux surgery is designed to
      improve the function of the antireflux barrier by reconstructing the physiology
      of the gastroesophageal junction. Studies have shown that a fundoplication
      procedure improves the strength and length of the lower esophageal sphincter and
      also restitutes the flutter valve mechanism. However, since gastroesophageal
      reflux disease is a common disorder, it is impossible for every patient to be
      attended by an expert surgeon, and this might be one important reason for the
      sometimes poor results presented after surgical treatment. When the question
      arises about which type of long-term therapy should be chosen in each clinical
      situation, this situation should also partly be influenced by some
      epidemiological information. If we assume that we expose a hypothetical group of
      100 patients with symptomatic, chronic severe reflux disease, also presenting
      endoscopic evidence of esophagitis of varying severity, available clinical
      information would suggest that only 25 can be considered suitable for antireflux
      surgery, depending on the frequently associated complicating medical disorders
      and the age distribution of the actual patient population. Therefore, it deserves
      to be emphasized that the majority of patients with complicated reflux disease
      are not fit for surgery and should consequently be managed medically. For younger
      patients with disabling GERD, antireflux surgery is still the gold standard and
      obviously very cost effective.

PMID- 7502534
TI  - The centenary of Lester Dragstedt--fifty years of therapeutic vagotomy.
AB  - Lester Reynolds Dragstedt was trained initially as a physiologist and
      subsequently became a surgeon. He achieved renown not only because of his
      intellectual and technical skills, but because he was able to utilize
      physiological principles to define the development of surgical procedures. A
      humble upbringing in Anaconda, Montana was followed by a scientific education in
      Chicago. His brief background in surgery was obtained during a two year period
      spent mostly in Vienna and Budapest. At the University of Chicago, he pioneered
      the development of therapeutic vagotomy in the treatment of peptic ulcer disease.
      His research interests were many and varied, ranging from the toxemia of
      intestinal obstruction to the quest for a pancreatic hormone which might regulate
      fat metabolism. After retiring as Chairman of Surgery at the University of
      Chicago, he assumed a research position in surgery at the University of Florida
      in Gainesville. Dragstedt was a creative scientist, a superlative clinical
      surgeon, and a teacher honored by his pupils. The example of his life confirms
      the benefit of scientific inquiry when applied to clinical and surgical practice.

PMID- 7502535
TI  - Gastric acid secretion: activation and inhibition.
AB  - Peripheral regulation of gastric acid secretion is initiated by the release of
      gastrin from the G cell. Gastrin then stimulates the cholecystokinin-B receptor
      on the enterochromaffin-like cell beginning a calcium signaling cascade. An
      exocytotic release of histamine follows with concomitant activation of a C1-
      current. The released histamine begins the H2-receptor mediated sequence of
      events in the parietal cell, which results in activation of the gastric H+/K+ -
      ATPase. This enzyme is the final common pathway of acid secretion. The H+/K+ -
      ATPase is composed of two subunits: the larger alpha-subunit couples ion
      transport to hydrolysis of ATP, the smaller beta-subunit is required for
      appropriate assembly of the holoenzyme. Both the membrane and extracytoplasmic
      domain contain the ion transport pathway, and therefore, this region is the
      target for the antisecretory drugs of the post-H2 era. The 100 kDa alpha-subunit
      has probably 10 membrane spanning segments with, therefore, five extracytoplasmic
      loops. The 35 kDA beta-subunit has a single membrane spanning segment, and most
      of this protein is extracytoplasmic with the six or seven N glycosylation
      consensus sequences occupied. Omeprazole is an acid-accumulated, acid-activated,
      prodrug that binds covalently to two cysteine residues at positions 813 (or 822)
      and 892, accessible from the acidic face of the pump. Lansoprazole binds to
      cys321, 813 (or 822) and 892; pantoprazole binds to cys813 and 822. The common
      binding site for these drugs (cys813 or 822) is responsible for the inhibition of
      acid transport. Covalent inhibition of the acid pump improves control of acid
      secretion, but since the effective half life of the inhibition in man is about 48
      hr, full inhibition of acid secretion, perhaps necessary for eradication of
      Helicobacter pylori in combination with a single antibiotic, will require
      prolongation of the effect of this class of drug.

PMID- 7502536
TI  - The history of acid inhibition.

PMID- 7502538
TI  - [Correlation between dietary behavior and educational attainment: results of the
      1984/85 nutrition survey of the Augsburg MONICA project].
AB  - The relationship between educational attainment and dietary behaviour was
      examined in a South German population of men aged 45 to 64 years. Analyses are
      based on data from the MONICA Augsburg Dietary Survey 1984/85 (7-day dietary
      records, n = 899). The evaluation of the daily food consumption shows that men
      with higher educational attainment prefer healthier food items than men with
      lower educational attainment. The healthier food pattern in men with higher
      educational attainment is reflected in a lower cholesterol intake and in a higher
      fibre intake. The mean daily intake of vitamins, minerals and trace elements is
      better in men with higher educational attainment with the exception of the
      vitamin niacin. The total daily caloric intake, fat intake and the combination of
      saturated, monounsaturated and polyunsaturated fatty acids is independent of
      educational attainment. The percentage of carbohydrates, protein and fat of the
      total caloric intake is nearly the same in all educational attainment groups. The
      results concerning food pattern and nutrient intake by educational attainment
      offer important information with regard to the development of strategies for the
      improvement of nutrition habits.

PMID- 7502539
TI  - Validation of a self-administered 24-hour recall questionnaire used in a large
      scale dietary survey.
AB  - This study investigated the relative validity of a self-administered 24-h recall
      questionnaire in a dietary survey on 3,653 men and women 7 years of age and
      older. The validation was carried out in a group of 41 men. An estimated dietary
      record kept over 3 days served as reference method. Comparison of the
      questionnaire and the estimated 3-day record showed good agreement. The Wilcoxon
      matched-pairs ranked signs test (p < 0.05) demonstrated that the only differences
      were the crude energy and carbohydrate intake and the estimated nutrient density
      of protein. The estimated proportion of calories from carbohydrate, fat, protein,
      and alcohol differed by no more than 2.4%. The median percentage differences in
      crude nutrient intakes and nutrient densities between the two assessment
      techniques ranged from -9% to 22%. The daily food intake differed significantly
      in only three of ten food groups. Spearman's correlation coefficients were higher
      than 0.35 for all density measurements. The highest correlation coefficients of
      about 0.60 were observed for alcohol and dietary fiber intake. It is concluded
      that the self-administered 24-hour recall questionnaire is a valid method for
      estimating the median and mean dietary intake of large groups of subjects.

PMID- 7502540
TI  - [Comparison of dietary surveys in Germany and Great Britain regarding objectives,
      methodology and results].
AB  - Referring to the data of the National Food Consumption Study in Germany and the
      Dietary and Nutritional Survey of British Adults, this article compares the food
      intake of German and British adults. Such a comparison is possible because both
      studies have mainly the same methodology. The comparison of the food intake of
      German and British adults points out food groups which Germans consume in higher
      amounts than British people do. To this category belong meat products and
      sausages, eggs, cheese and cottage cheese, butter, fat for cooking and salad oil,
      bread and pastries, vegetables, fruit, preserves and soft drinks. The Germans
      consume less meat, fish and fish products, milk and milk products, pasta, rice
      and miscellaneous cereals, potatoes, sugar, sweets and tea than the British
      people do. The consumption of fruit products, alcoholic beverages and coffee is
      nearly the same in Germany and Great Britain.

PMID- 7502537
TI  - [Antioxidative vitamins and cataracts in the elderly].
AB  - Senile cataract indicates the opacity of ocular lenses occurring in old and
      especially in very old people. Lens proteins are extremely long-living and often
      show oxidative damages. Aging and smoking appear to be the greatest risk factors
      for the development of lens opacities. The sufficient antioxidant protection of
      young lenses decreases with the aging process. Consequently, the importance of
      other protective factors increases. Nutritional factors, particularly vitamins
      with antioxidant properties, may influence the development of senile cataracts in
      the ocular lens. Meanwhile an association between the supply with vitamin C, E
      and beta-carotene and the risk of cataract development was demonstrated in animal
      studies and also in an increasing number of epidemiological studies. These
      epidemiological studies mainly support the hypothesis that higher vitamin intakes
      reduce the risk of developing cataracts in old age. The antioxidant properties of
      the named nutrients give a plausible explanation for the mechanism of
      cataractogenesis. On the basis of the present data definitive recommendation,
      necessary for cataract prevention can not yet be established. Some results seem
      to support higher recommendations. At the moment several large human intervention
      trials are carried out. Form these studies a further confirmation of the
      antioxidant hypothesis and of a dose-response-relationship are expected.

PMID- 7502541
TI  - [Reducing lipid peroxidation of stored frozen trout fillet by supplementing feed
      with vitamin E].
AB  - Rainbow trouts were fed a complete diet with 12 mg vitamin K3 and supplemented
      with 20, 200 or 2,000 mg all-rac-alpha-tocopheryl-acetate/kg for 18 weeks. The
      ratio of the vitamin E-supplementation was 1:10:100. Fillets were minced and
      stored at -18 degrees C. Concentrations of alpha-tocopherol and phylloquinone and
      parameters of lipid peroxidation were measured after 4, 6, and 8 months of
      storage. The effects of alpha-tocopherol incorporated into fillets on storage
      stability were assessed by measuring free fatty acids, peroxides, malondialdehyde
      and lipofuscin. Mean alpha-tocopherol-concentrations in fillets were 1.4, 2.7 and
      16.3 mg/100 g, respectively representing ratios of 1:2:12. The increase in alpha
      tocopherol concentration resulted in a significant improvement of storage
      stability. The phylloquinone concentration in fillet was reduced in treatments
      with > or = 200 mg vitamin E/kg; however, this did not affect the prothrombin
      time. No peroxides were detectable at any time. The concentrations of
      malondialdehyde significantly decreased with increasing supplementation of
      vitamin E. Lipofuscin concentrations were higher with low than with high vitamin
      E supplementation. The dose-related inhibition of lipid peroxidation became
      apparent in decreased concentrations of free fatty acids in the crude fat. These
      results confirm the effectiveness of alpha-tocopherol as antioxidant in fish
      flesh. In this study the incorporation of alpha-tocopherol from dietary
      supplementation improved the long-term storage quality of trout fillets due to
      the effective inhibition of the lipid peroxidation. A measurable improvement of
      the storage stability was achieved with a supplementation of 200 mg vitamin E/kg
      feed.

PMID- 7502542
TI  - [Thermogenesis in overfeeding with administration of olive oil and fish oil in a
      swine model study].
AB  - A trial on total metabolism was conducted in eight nonpregnant, nonlactating sows
      over eight periods, each of 16 days duration, to measure potential fatty acid
      induced thermogenesis. During the first and last experimental periods, the
      animals received a basal ration which just covered the energy maintenance
      requirement. In the second to seventh periods supplements of olive oil, fish oil,
      or puffed wheat starch as reference nutrient were added to the diet in random
      sequence at two levels up to 50% above the maintenance requirement. All rations
      were calculated with reference to the sows' initial weight and remained
      quantitatively unchanged throughout the experiment. The animals were fed twice
      daily. During each metabolism period a complete energy balance was assessed for
      all sows by means of collection technique (feed, feces, urine), and 48-h
      measurements of the gas exchange in a respiration chamber. The sows' body mass
      increased linearly during the course of the experiment by 5.8 kg per period. The
      three supplement types had no influence on the animals' final body weight, wich
      averaged 205.5 kg with the starch supplement, 204.8 kg with olive oil, and 205.8
      kg with fish oil. Energy digestibility (DE/GE) was 100% for all three
      supplements, and metabolizability of energy (ME/GE) one percentage point less.
      Carbon and energy depositions showed a pronounced linear relationship to the
      level of supplementation and were also influenced by the type of supplement. Heat
      production was 20.9 MJ/d after feeding the basal ration alone and, taking the
      average of the two supplementation levels, 21.6 MJ for the starch supplement,
      21.0 MJ for olive oil, and 20.6 MJ for fish oil.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502543
TI  - Circadian anorectic effects of peripherally administered amylin in rats.
AB  - The pancreatic peptide amylin (1 microgram/kg) injected intraperitoneally reduced
      cumulative food intake for up to 4 h in food-deprived (24 h) and non-deprived
      rats at various times of the day, i.e., at dark onset, in the middle of the dark
      phase, and at light onset. At none of these times did subdiaphragmatic vagotomy
      abolish the anorectic effect of amylin. Rather, vagotomy enhanced, by unknown
      mechanisms, amylin's anorectic effect in food-deprived rats at light onset and in
      the middle of the dark phase. In contrast to previous studies with older rats,
      amylin's anorectic effect was also observed when injected into nondeprived rats.
      The findings of the present study extend previous reports in that amylin's
      anorectic effect, not being abolished by abdominal vagotomy after intraperitoneal
      injection, can be elicited at different times of the day.

PMID- 7502544
TI  - The effect of graded ascorbic acid intake on the activity of GSH-Px in the liver
      of female guinea pigs.
AB  - Differing antioxidant potentials created by graded ascorbic acid supplementation
      (1, 10, 100 mg per animal daily) evoked changes in the level of glutathione
      peroxidase activity and lipid peroxides in the liver of female guinea pigs. The
      group with the lowest ascorbic acid intake (1 mg) had the lowest activity of
      glutathione peroxidase and the highest level of lipid peroxides. The two other
      groups (10 and 100 mg) showed enhancement of glutathione peroxidase activity and
      decline in lipid peroxides. There was no difference between the groups with 10
      and 100 mg ascorbic acid intake.

PMID- 7502545
TI  - Effect of dietary canola oil and its degree of oxidation on exocrine pancreatic
      secretions in growing pigs.
AB  - Four barrows, average initial weight 35 kg, were fitted with permanent pancreatic
      re-entrant cannulas and used to determine the effect of level and quality of
      dietary fat on exocrine pancreatic secretions. The pigs were fed four corn starch
      based diets that contained 15% crude protein from isolated soy protein. Diet 1
      contained no canola oil (C-0); diet 2, 15% canola oil (C-15); diet 3, 15% canola
      oil that was heated under vacuum at 180 degrees C for 12 h (C-15/12); diet 4, 15%
      canola oil that was heated under vacuum at 180 degrees C for 24 h (C-15/24). Heat
      treatment resulted in a 4- to 5-fold increase in the content of malonaldehyde
      which is derived from the oxidation of fatty acids and which is closely related
      to odour and rancidity in lipids. The experiment was carried out according to a 4
      x 4 Latin square design. The pigs were fed twice daily, at 08:00 and 20:00 h, 900
      g each meal. Following an adaptation period of 7 d, pancreatic juice was
      collected continuously for 24 h at 2-h intervals from 08:00 on d 8 until 08:00 on
      d 9 and from 08:00 on d 10 until 08:00 on d 11 during each experimental period.
      The volume of secretion of pancreatic juice peaked 6-10 h postprandially and was
      similar (P > .05) during day (08:00-20:00 h) and night (20:00-08:00 h).
      Replacement of 15% starch by 15% canola oil resulted in a decrease (P < .05) in
      the secretion of alpha-amylase and an increase (P < .05) in the secretion of
      lipase. The inclusion of oxidized fat caused a further increase (P < .05) in
      total lipase activities. It can be concluded that the exocrine pancreas is able
      to adapt to variations in the level and quality of dietary lipids.

PMID- 7502547
TI  - [An approach for planning hospital menus using a knowledge-based system].
AB  - Menu planning in hospitals is a complex decision problem. Patients expect the
      menu plan to be healthful and in accordance with their nutritional habits.
      Furthermore, the menu plan must conform to capacity limits of the kitchen. In
      this paper we present an approach to computerized food selection and menu
      composition. The model is based on nutritional knowledge, which is represented in
      the computer and used for problem solving.

PMID- 7502546
TI  - [Modification of fecal bile acid excretion by fish oil in healthy probands].
AB  - Several studies indicated a protective effect of fish oil on colon carcinogenesis
      which might be due to alterations in prostaglandin E2 synthesis of the colonic
      mucosa. Additional effects on fecal bile acid excretion may also play a role
      since especially secondary bile acids are known to act as promoters in colon
      cancer development. In the present study possible influences on bile acid
      excretion were investigated in 12 healthy volunteers whose daily diet was
      supplemented for 4 weeks with 11 g of fish oil (FO) and corn oil (CO) per day,
      respectively. Fecal bile acids were analyzed by gas-liquid-chromatography. Fecal
      excretion of total bile acids was not different during the periods of FO and CO
      supplementation (301.9 vs. 320.3 mg/day). However, a non-significant trend to a
      lower daily excretion of the secondary bile acid lithocholic acid was found after
      FO compared to CO-ingestion (99.6 vs. 109.4 mg/day; p = 0.22). Since secondary
      bile acids are known promoters of colon carcinogenesis, these findings may
      implicate a favorable situation with respect to colon cancer prevention.

PMID- 7502548
TI  - Iodine concentration in canteen meals prepared with or without iodized salt.
AB  - In each of two university canteens differing in the use (canteen A) or non-use
      (canteen B) of iodized salt for food preparation, 15 mostly equal lunch meals
      were collected for iodide and NaCl analysis. With similar NaCl content, the meals
      of canteen A contained on average 6.1 micrograms I/100 g ww (8.5 micrograms I/g
      NaCl) more I than the meals of canteen B. Total I intake by consumption of an
      average meal of canteen A was estimated as 56.5 +/- 24.1 micrograms (canteen B:
      17.0 +/- 9.9 micrograms). Consequently, the use of iodized salt in central
      catering seems to play a more important role in a sufficient I intake than
      assumed so far.

PMID- 7502549
TI  - Comparison between high dose 5-aminosalicylic acid and 6-methylprednisolone in
      active Crohn's ileocolitis. A multicenter randomized double-blind study. German 5
      ASA Study Group.
AB  - BACKGROUND: The value of 5-aminosalicylic acid (5-ASA) in Crohn's disease (CD) is
      still under discussion. In a previous study 2 g 5-ASA per day were inferior to a
      standard glucocorticoid treatment with 6-methylprednisolone (6-MPred) (Can J
      Gastroenterol 1990; 4: 446-51). In the present study we tested whether in active
      CD response rates to 4.5 g 5-ASA/day were not different from those to 6-MPred.
      METHODS: Multicenter randomized double-blind double-dummy trial. 34 patients with
      active CD (CDAI > 150) were included. 17 patients were in the 5-ASA group
      (Salofalk, 4.5 g/day), 17 patients in the 6-MPred group (Urbason, initial dose 48
      mg/day, weekly tapering). Duration of treatment was 8 weeks. Main outcome measure
      was remission of CD (CDAI < 150) and decrease of at least 60 points. RESULTS:
      Both groups were comparable with respect to demographic and clinical parameters.
      The median CDAI decrease in the 5-ASA group was 85, in the 6-MPred group 122 (p =
      0.7437). The median AUC of the CDAI in the 5-ASA group was 1027, in the 6-MPred
      group 950 (p = 0.137). The median AUC of the CDAI per treatment day was 22.94 in
      the 5-ASA group, and 17.33 in the 6-MPred group (p = 0.0555). On an intention-to
      treat basis remission rates after 8 weeks were 40.0% in the 5-ASA group and 56.3%
      in the 6-MPred group (p = 0.5867). CONCLUSIONS: Response rates to 5-ASA or 6
      MPred were not significantly different although there was a trend towards a
      higher efficacy of 6-MPred. 5-ASA may be considered as alternative treatment in
      patients with activer CD who are intolerant to or refuse glucocorticoids.

PMID- 7502550
TI  - Simvastatin added to ursodeoxycholic acid does not enhance disappearance of
      gallstone fragments after shock wave therapy.
AB  - Inhibitors of the HMG-CoA reductase have been shown to further reduce the biliary
      cholesterol saturation in patients treated with oral bile acids for cholesterol
      gallbladder stones. It was the aim of our study to evaluate the efficacy of
      simvastatin in addition to ursodeoxycholic acid in the dissolution of gallstone
      fragments after shock wave lithotripsy and adjuvant bile acid dissolution
      therapy. Eighteen patients with a single radiolucent gallbladder stone and a
      serum cholesterol of more than 250 mg/dl were randomly assigned to receive either
      ursodeoxycholic acid alone (750 mg per day, group A, n = 9) or in combination
      with simvastatin (20 mg per day, group B, n = 9) for the dissolution of the
      gallstone fragments generated by extracorporeal shock wave lithotripsy. The two
      groups were well matched regarding their baseline characteristics. At the primary
      end point of the study 6 months after lithotripsy, there was no difference
      between the groups in the rate of gallstone disappearance with 4 of 9 patients
      being stone free in each group. As evaluated by life table analysis, even further
      follow-up showed no significant difference between the groups (P = 0.8). In group
      B, serum cholesterol levels decreased by 22% at 3 months (P = 0.01 vs. baseline)
      and by 24% at six months (P = 0.02) during treatment while no significant change
      was observed in group A. With both regiments, no adverse effects were observed.
      While simvastatin added to ursodeoxycholic acid resulted in a decrease of
      elevated serum cholesterol levels in gallstone patients, it did not enhance stone
      disappearance after shock wave lithotripsy and adjuvant bile acid dissolution
      therapy.

PMID- 7502552
TI  - [The 100th birthday of Heinz Kalk. A breakthrough in laparoscopy].
AB  - The method of laparoscopy, mainly being introduced as a diagnostic tool, has
      developed into an important therapeutic procedure during the last decade. This
      development is associated with the name of the German gastroenterologist Heinz
      Kalk. Born in Frankfurt/Main in 1895 he first published about laparoscopy in 1929
      and also designed a new laparoscope with a prograde optic. He realized the great
      value of laparoscopy in the differential diagnosis of liver diseases. During the
      40's Kalk introduced laparoscopically guided liver biopsy and was involved to a
      great extent in research of hepatic diseases, especially Hepatitis epidemica. The
      work of Kalk was of decisive influence for the development of laparoscopy in
      Europe. In 1949 he became chief of the Department of Internal Medicine of
      Kassel's hospital "Stadtkrankenhaus", making it one of the most interesting
      places to be in for hepatologists and laparoscopically working internists. Heinz
      Kalk died in 1973.

PMID- 7502551
TI  - Omeprazole/amoxicillin versus triple therapy for Helicobacter pylori in duodenal
      ulcer disease: two-year follow-up of a prospective randomized study.
AB  - The present study was designed to compare the efficacy and tolerability of triple
      therapy and dual therapy for Helicobacter pylori in duodenal ulcer patients and
      to evaluate the long-term clinical course of ulcer disease. Forty duodenal ulcer
      patients with proven H. pylori infection were enrolled into the study and
      randomly treated with either triple therapy consisting of bismuth subsalicylate,
      metronidazole and tetracycline plus ranitidine or with dual therapy comprising
      omeprazole and amoxicillin. Patients were investigated clinically and
      endoscopically including assessment of H. pylori infection by means or rapid
      urease test, culture, histology and urea breath testing 4 weeks after cessation
      of eradication therapy, in 1-year intervals and when dyspeptic symptoms recurred.
      One patient of each group was lost during follow-up. H. pylori infection was
      cured by triple therapy in 84.2% and by dual therapy in 78.9% (p = 1.00). During
      follow-up, all patients with cure of H. pylori infection (n = 31) remained in
      stable remission with respect to duodenal ulcer disease, while 6 out of 7
      patients persistently infected with H. pylori developed an ulcer relapse (p <
      0.001). One patient with cured infection had had an episode of dyspeptic symptoms
      requiring pharmacotherapy and in another 3 patients mild refluxesophagitis
      without necessity of medical treatment had been detected on the occasion of a
      scheduled endoscopy. In the short-term, cure of the infection resulted in a
      marked reduction of the degree of antral gastritis and in a loss of activity in
      all but one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502553
TI  - [Helicobacter pylori and peptic ulcer--1995 therapeutic indications and
      recommendations of a Munster Expert Group].

PMID- 7502554
TI  - Arterial pseudoaneurysm as a complication of percutaneous transhepatic biliary
      drainage: treatment by embolization.
AB  - We observed a serious arterial hemorrhage as a complication of percutaneous
      transhepatic biliary drainage (PTBD). The hemorrhage appeared during catheter
      placement for implantation of an endobiliary stent as a two-step procedure. It
      was caused by an arterial pseudoaneurysm and could be successfully treated by
      superselective embolization. Although there was a preexisting cavernous
      transformation of the portal vein no signs of liver cell necrosis appeared after
      embolotherapy. Vascular complications of PTBD will be discussed with regard to
      their frequency, possible etiology, ways to avoid them and their interventional
      therapy.

PMID- 7502555
TI  - Endoscopic (-ERC) fibrin sealing and histoacryl sealing of an abscess induced
      bilio-hepatico-cutaneous and a bilio-hepatico-phrenico-bronchial fistulous
      system.
AB  - We report the case of a female patient with persisting bilio-bronchial and bilio
      cutaneous fistulae originating in the right liver lobe. The causative factor was
      a subphrenic liver abscess which had been adequately and successfully treated. No
      biliary obstruction was detectable on admission. Because of her previous medical
      history the patient was considered to be a high surgical risk. Therefore the
      described endoscopic (ERC) approach was chosen. Here we describe the first
      successful attempt to close such a fistulous system by repeated fibrin and
      histoacryl-sealing through an endoscopically guided catheter. The success of this
      innovative procedure may be helpful, in the management of similar cases in the
      future.

PMID- 7502556
TI  - Gastric carcinoma arising from a hyperplasiogenic polyp with a diameter of less
      than 2 centimeters.
AB  - As there are only few reports on the occurrence of carcinoma in hyperplasiogenic
      polyps there is at present no general agreement concerning the malignant potency
      of these polyps in the stomach. In this paper we review the literature and
      present the unusual case of a patient who developed carcinoma in a
      hyperplasiogenic polyp with a diameter of 15 x 5 mm. Whereas in nearly all the
      reported cases cancer developed in polyps with a diameter greater than 2 cm our
      findings demonstrate that even in smaller polyps malignant changes have to be
      suspected.

PMID- 7502557
TI  - Parenchymal and nonparenchymal liver cells and their interaction in the local
      immune response.
AB  - Nonparenchymal liver cells (Kupffer cells, sinusoidal endothelial cells, Ito
      cells and liver-associated lymphocytes) interact with hepatocytes and with each
      other by soluble mediators and direct cell-cell contact. The acute phase response
      is a nonspecific reaction of the organism to trauma, injury or infection and its
      main constituents the acute phase proteins are produced by hepatocytes. The
      profile of acute phase protein production is influenced by the local presence of
      cytokines with IL-6 as the principal regulator. Nonparenchymal cells (Kupffer
      cells, sinusoidal endothelial cells and Ito-cells) are a source of IL-6 and
      therefore participate in the generation of acute phase response. The release of
      IL-10 by Kupffer cells with consecutive down-regulation of IL-6 production may be
      a mechanism by which resolution of acute phase response is achieved. Still, the
      mechanisms underlying chronic inflammation remain unclear. Concerning the antigen
      specific immune response nonparenchymal liver cells have a number of important
      functions. They can act as antigen-presenting cells (Kupffer cells) or mediate
      effector functions (liver associated lymphocytes). Local interaction of
      nonparenchymal cells with hepatocytes can be mediated by cytokines and/or
      adhesion molecule expression which again may lead to mutual influence of
      immunological functions, e.g. TNF-alpha release by Kupffer cells may enhance MHC
      II expression on hepatocytes and consequently augment antigen-presenting capacity
      leading to an improved antigen-specific immune response. Leukocytes are attracted
      and home to the liver by mechanisms poorly defined because the initial contact
      between leukocytes and macrovascular endothelium.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7502558
TI  - [Omeprazole + clarithromycin + metronidazole--a new standard for eradication of
      Helicobacter pylori].

PMID- 7502560
TI  - [Long-term follow-up of hepatitis B virus infected patients after orthotopic
      liver transplantation].

PMID- 7502559
TI  - [Comparison between tacrolimus (FK 506) and cyclosporin in immunosuppressive
      therapy after liver transplantation].

PMID- 7502561
TI  - [Clonal analysis of regenerating nodules in hepatitis C-induced liver cirrhosis].

PMID- 7502562
TI  - [The IGF-I receptor: a new antiproliferative marker?].

PMID- 7502563
TI  - [Diagnosis of colonic polyps and tumors by hydrosonography].

PMID- 7502564
TI  - [How do you want to die? The therapeutic options in ventricular tachyarrhythmia
      at the end of the anti-arrhythmia drug era].

PMID- 7502565
TI  - [Experimental approaches for gene therapy modification of vascular remodeling].
AB  - The active process of vascular remodeling involves changes in several cellular
      processes like cell growth, cell death, cell migration, and extracellular matrix
      production or degradation. The recent development of in vivo gene transfer
      technology has created a powerful new tool for the study of vascular remodeling
      by providing methods to overexpress or to inhibit specific local factors which
      are believed to contribute to the process of structural changes within the
      vasculature. The following overview describes recently published studies which
      investigated the effects of gene overexpression or inhibition on the process of
      vascular remodeling. The technology of gene transfer provides the opportunity for
      the development of novel therapeutic strategies such as gene replacement, gene
      correction, or gene augmentation, thus paving the way for gene therapy as
      treatment for vascular disease.

PMID- 7502566
TI  - [Cerebral ischemia during implantation of automatic defibrillators].
AB  - In order to study the influence of repetitive episodes of ventricular
      fibrillation (VF) during defibrillator implantation on the electrical activity of
      the brain, we performed an electroencephalographic (EEG) monitoring during
      implantation procedure in 18 patients. For defibrillation threshold testing 62
      episodes of VF (1-6 episodes per patient) were induced. The mean duration of VF
      was 20 +/- 12 s; the mean duration of hypotension during an episode (defined as a
      mean arterial pressure of 50 mm Hg or less) was 33 +/- 16 s. EEG monitoring was
      performed using the International 10-20 System. The duration of cardiac arrest
      related EEG alteration was assessed by an experienced neurologist and could be
      determined in 41 test-episodes; in 21 episodes analysis was not possible due to
      poor recordings. Ischemia-related EEG changes started 7.8 +/- 4.6 s after VF
      induction and lasted 64 +/- 49 s (range, 12-240). The duration of EEG alteration
      was significantly (p < .001) correlated with the duration of VF episodes (r =
      .71) and the associated hypotension (r = .82). With regard to patients the
      duration of ischemia related EEG changes also correlated significantly (p = .001)
      with the individual cumulative duration of VF (r = .85) and the associated
      hypotension (r = .88). In females EEG changes lasted longer than in males (p =
      .03); this finding, however, was only based on 2 women. Other clinical
      parameters, such as patient age, degree of congestive heart failure, left
      ventricular ejection fraction, stroke volume and cardiac index, the order of
      episodes within the testing sequence, and the time interval between episodes did
      not correlate with the duration of EEG alteration after VF induction. The
      duration of ischemia-related EEG alteration during VF episodes depends on the
      duration of cardiac arrest. In females EEG changes tended to last longer than in
      males, however, this finding has to be confirmed. An association with other
      clinical parameters has not been observed. Limitation of VF duration appears to
      be the most important factor to avoid prolonged cerebral ischemia.

PMID- 7502567
TI  - [Cerebrogenic ECG changes after severe subarachnoid hemorrhage from an internal
      carotid artery aneurysm--differential diagnosis of acute myocardial infarct].
AB  - ECG-changes simulating acute posterior myocardial infarction were observed in a
      62-year-old woman 16 days after acute subarachnoid hemorrhage. An acute
      myocardial ischemia was excluded by enzyme laboratory tests and by coronary
      angiography. The transient ECG-changes can be explained by short-term spasms of
      small distal arterioles in the heart, which were affected by a derangement of
      autonomic function. The present case demonstrates ECG-changes in a patient with
      subarachnoid hemorrhage very late after the acute event. Therefore, patients with
      intracranial hemorrhage should have a prolonged electrocardiographical aftercare.
      ECG-changes in patients with subarachnoid hemorrhage were discussed as a specific
      parameter describing the degree of intracranial damage and as a predictive value
      for a poor outcome. Because of ventricular arrhythmias and the occurrence of
      sudden cardiac death in patients with subarachnoid hemorrhage critical care
      monitoring should be performed after detection of new ECG-changes.

PMID- 7502568
TI  - [High frequency catheter ablation in AV-nodal reentry tachycardia: clinical
      significance of slow pathway potentials and junctional tachycardia].
AB  - During slow pathway-ablation of AV nodal reentrant tachycardia (AVNRT) with a
      mean cycle length of 355 +/- 70 ms the clinical significance of slow pathway
      electrograms (SP-EGM) and junctional tachycardias (JT) was evaluated in 39
      patients (9 male, 30 female; mean age 57 +/- 15 years). After two patients were
      excluded from further investigation because of inadvertent procedural complete
      heart block, typical SP-EGM were recorded in 30/37 patients (81%) before
      successful RF administration in the posteroseptal portion of the right atrium.
      Signals were recorded 61 +/- 22 and 34 +/- 24 ms after atrial activation in the
      His bundle and proximal coronary sinus catheter, respectively. Additionally,
      timing was noted 15 +/- 10 ms before the His spike; the duration of SP-EGM was 27
      +/- 7 ms, and the A/V relation of the SP-EGM was calculated as 0.59 +/- 0.51 in
      the ablation bipole. JT was observed in 24/37 patients (78%), with a mean cycle
      length of 511 +/- 92 ms. The first tachycardia beat appeared initially 4.1 +/-
      3.8 s after delivery of the successful RF administration and lasted 18 +/- 8 s.
      In 14/37 patients (38%) either SP-EGM or JT was missing; in one patient neither
      of these two was recorded despite successful ablative therapy. The success rate,
      defined by noninducibility of AVNRT, was 95% (35/37). In 11% (4/37) AVNRT
      recurred during a mean follow-up of 5 +/- 4 months. In summary, SP-EGM and JT
      were recorded reproducibly and proved to be a useful tool as electrographic
      mapping approach of slow pathway ablation in AVNRT.

PMID- 7502569
TI  - [Beta receptor blockers in chronic heart failure].
AB  - Recently published data of the controlled MDC- and CIBIS-trials confirm the
      favorable effect of beta-blocker therapy on the hemodynamics and clinical course
      of patients with chronic heart failure due to dilatated and/or ischemic
      cardiomyopathy. However, mortality remains unchanged. The mechanisms by which
      beta-blocker therapy improves hemodynamics in chronic heart failure are not known
      reliably. It is postulated that the negative chronotropic effect of beta-blockers
      improves the cellular calcium metabolism and thereby increases myocardial
      contractility. Further effects of beta-blockers are protection of myocardial
      cells from enhanced catecholamine concentrations. This prevents cell necrosis and
      economizes the use of cell energy. The reversion of down-regulation of beta-1
      receptors in beta-blocker therapy is most probably only an epiphenomenon. Major
      randomized clinical trials are ongoing to investigate whether improved
      hemodynamics and clinical course are correlated with decreased mortality. It also
      still remains open which substance is most beneficial (e.g., selective beta
      blockers, beta-blockers with additional vasodilatatory effect).

PMID- 7502570
TI  - [Acute hemodynamic effects of piroximone i.v. in patients with severe heart
      failure].
AB  - Forty patients (30 men, 10 women) with severe congestive heart failure NYHA III
      (n = 30) and IV (n = 10) due to coronary heart disease (n = 19) or dilative
      cardiomyopathy (n = 21) were enrolled in this study. Mean age was 57 years. Eight
      patients each received 0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg piroximone
      intravenously or placebo (saline). Measurements were performed before and up to 4
      h after drug administration using a Swan-Ganz right-heart thermodilution
      catheter. RESULTS: All changes stated were significant (p < 0.05). Pulmonary
      capillary wedge pressure was lowered by max. 27% (0.25 mg/kg) to 52% (2.0 mg/kg)
      30 min after drug injection. Significant effects were seen for 60 (0.25 mg/kg) to
      120 min (2.0 mg/kg). Mean pulmonary artery pressure decreased by max. 8% to 24%
      after 30 min. Effects lasted for 30 to 60 min. Cardiac index increased by max.
      26% to 52% after 30 min. Significant changes occurred up to 4 h after 2.0 mg/kg.
      Systemic vascular resistance fell by max. 16% to 34%. Effect duration was 1 h
      (0.5 mg/kg up to 4 h) (2.0 mg/kg). Minor changes of arterial blood pressure
      (minus 7% after 0.5 mg/kg) and heart rate (minus 14% after 2.0 mg/kg) were seen.
      CONCLUSION: Small doses of piroximone i.v. increase cardiac output by about 20%
      while preload and afterload decrease by about 20%. For most cases no doses higher
      than 0.5 mg/kg will be needed for the treatment of severe congestive heart
      failure.

PMID- 7502571
TI  - [Chronic frequency-adaptive pacemaker therapy in patients with heart failure].
AB  - Twenty patients (complete AV block n = 13, sick sinus syndrome n = 4 (replacement
      of a VVI system), bradyarrhythmia n = 3) with rate-adaptive pacemakers
      (respiration volume guided n = 10, QT-driven n = 1, dual sensor (QT/activity)
      system n = 9) were randomly assessed by ergospirometry after 4 weeks of VVI- (70
      bpm), VVIR1-(70-110 bpm, low upper rate) and VVIR2-pacing (70-130 bpm, high upper
      rate). Oxygen uptake (VO2), work load (W), and heart rate were determined at peak
      exercise (max) and at the anaerobic threshold (AT). In the whole population, rate
      adaptation led to a significantly higher VO2-max than VVI-pacing for both VVIR1-
      (15.5 +/- 5.1/12.6 +/- 4.1 ml/kg/min, 28 +/- 37%, p < 0.01) and VVIR2-pacing
      (14.8 +/- 4.4/12.6 +/- 4.1 ml/kg/min, 20 +/- 23%, p < 0.01). At the AT, however,
      VO2 was significantly improved only by the VVIR1 mode (low upper rate, 9.8 +/-
      2.5/8.0 +/- 2.1 ml/kg/min, 28 +/- 36%, p < 0.01). Regarding only patients with
      moderately limited exercise capacities (Weber class C, n = 11), rate adaptive
      VVIR1 and VVIR2 pacing could not produce a significant increase of VO2-max and
      VO2-AT. In contrast, patients with severely reduced exercise capacities (Weber
      class D, n = 9) significantly profited from the rate adaptation, but only in the
      VVIR1 mode (VO2-max 48 +/- 45%, VO2-AT 51 +/- 38%, p < 0.01). Thus, in the whole
      population an increase of oxygen uptake and of exercise workload at the anaerobic
      threshold could only be achieved by pacing with the low upper rate of 110 bpm. By
      this, particularly patients with heart failure and a severely limited exercise
      tolerance (Weber D) had a significant benefit. Therefore, the upper rate should
      be programmed in a lower range in patients with heart failure, at least for rate
      adaptive ventricular pacemaker systems.

PMID- 7502572
TI  - [Reliability of digital transesophageal echocardiography in imaging the left
      coronary artery].
AB  - Fifty consecutive patients (mean age 56 years) were examined to evaluate the
      reliability of transesophageal echocardiography in the evaluation of the left
      proximal coronary artery. Results of 28 cases were compared to selective coronary
      angiography. Echocardiography was able to visualize the left main artery for the
      length of 1.0 +/- 0.6 cm in all patients (100%), the left circumflex artery for
      maximal 3.1 +/- 1.4 cm in 86% and the left anterior descending artery as long as
      2.3 +/- 0.9 cm in 58%. The intraluminal diameter of the most proximal localized
      segments measured by echocardiography and angiography in the LAO and RAO
      projection was in terms of the left main artery 4.1 +/- 0.9 mm, 4.1 +/- 0.9 mm
      and 4.0 +/- 0.9 mm (n.s.), of the left circumflex artery 2.8 +/- 0.5 mm, 3.3 +/-
      0.8 mm and 3.3 +/- 0.9 mm (n.s.) and of the left anterior descending artery 3.0
      +/- 0.8 mm, 3.4 +/- 0.7 mm, and 3.6 +/- 1.0 mm (n.s.). In respect of detection of
      coronary artery stenoses in correspondence to the coronary angiogram sensitivity
      was 81%, specificity 93% and positive predictive accuracy 86%. Quantitative
      analyses of the coronary anatomy and the correlation to angiography could
      contribute to the validation of transoesophageal echocardiography.

PMID- 7502573
TI  - Myocardial contrast echocardiography for assessment of papaverine vasodilator
      response in patients with angiographically normal coronary arteries and in
      patients after orthotopic heart transplantation.
AB  - Myocardial contrast echocardiography has the potential for assessing changes in
      regional myocardial perfusion. We used this method to compare papaverine
      vasodilator response in 10 patients after orthotopic heart transplantation
      without acute rejection of left ventricular hypertrophy (HTX) and in 15 patients
      with angiographically normal coronary arteries (control group). Injections of 2
      ml of sonicated iopromid (9 paired injections in HTX and 24 paired injections in
      the control group) were performed before and after intracoronary application of
      papaverine (8 or 10 mg) into the left or right coronary artery. From regional
      time-intensity curves, alpha (variable of curve width), area under the curve
      (area), peak contrast intensity (Imax) and contrast decay half-time (T1/2) were
      derived by from a gamma variate function. T1/2 increased from 4.2 +/- 1.2 to 7.2
      +/- 4.0 s (p < 0.01) after papaverine in HTX compared to a change from 4.8 +/-
      1.0 to 6.0 +/- 1.7 s (p < 0.001) in normal subjects. Alpha decreased in HTX from
      0.44 +/- 0.15 to 0.27 +/- 0.10 s-1 (p < 0.01) after intracoronary papaverine
      injection. In the control group alpha was 0.37 +/- 0.08 s-1 at rest compared to
      0.30 +/- 0.08 s-1 at hyperemic conditions (p < 0.002). Area increased in HTX from
      444 +/- 261 to 910 +/- 732 U.s (p < 0.01) and in normal subjects from 352 +/- 171
      to 585 +/- 262 U.s (p < 0.001). Hyperemic to baseline flow ratios for area varied
      from 0.9 to 3.8 (mean 2.17 +/- 1.11) in HTX compared to 1.76 +/- 0.52 (1.03 to
      2.71) in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502574
TI  - [Management of an iliac artery aneurysm with percutaneous placement of a Dacron
      nitinol vascular endoprosthesis].
AB  - An iliac aneurysm developed after local lysis and balloon dilatation of the left
      iliofemoral arteries in a 66-year old male patient. This led to arterial
      embolism. A self-expanding Dacron-Nitinol vascular endoprosthesis was inserted
      without surgery. In this way, the aneurysm was isolated from the circulation.

PMID- 7502575
TI  - [Sotalol-induced torsade de pointes tachycardia in a 15-month-old infant].
AB  - Torsade de pointes (tdp) is a form of ventricular tachycardia whose occurrence in
      childhood is very rare. In adults treated with sotalol (Sotalex), tdp has been
      reported to have an incidence of 2-4%. There have been no reports of its
      occurrence in children treated with sotalol. We report about a 15-month-old girl
      with Wolff-Parkinson-White syndrome who developed recurrent syncopal attacks. She
      had been treated with sotalol at 1.5 mg/kg daily since being a newborn because of
      recurrent episodes of paroxysmal supraventricular tachycardia. Electrocardiogram
      exhibited frequent tdp tachycardia. Serum electrolyte levels were normal.
      Echocardiography excluded a structural heart defect and showed no signs of
      myocardial infection. After sotalol was ceased, infusion with lidocain was
      started. Despite this therapy the tdp continued. Magnesium aspartate
      (Magnesiocard) was then administered, and this finally stopped the tdp. As no
      other cause was evident, tdp in this child must be judged as a proarrhythmia
      related to sotalol therapy.

PMID- 7502576
TI  - Review: the dominant flocculation genes of Saccharomyces cerevisiae constitute a
      new subtelomeric gene family.
AB  - The quality of brewing strains is, in large part, determined by their
      flocculation properties. By classical genetics, several dominant, semidominant
      and recessive flocculation genes have been recognized. Recent results of
      experiments to localize the flocculation genes FLO5 and FLO8, combined with the
      in silicio analysis of the available sequence data of the yeast genome, have
      revealed that the flocculation genes belong to a family which comprises at least
      four genes and three pseudogenes. All members of this gene family are located
      near the end of chromosomes, just like the SUC, MEL and MAL genes, which are also
      important for good quality baking or brewing strains. Transcription of the
      flocculation genes is repressed by several regulatory genes. In addition, a
      number of genes have been found which cause cell aggregation upon disruption or
      overexpression in an as yet unknown manner. In total, 33 genes have been reported
      that are involved in flocculation or cell aggregation.

PMID- 7502577
TI  - Isolation and characterization of a novel yeast gene, ATH1, that is required for
      vacuolar acid trehalase activity.
AB  - We have isolated a plasmid containing a gene, ATH1, that results in eight- to ten
      fold higher acid trehalase activity in yeast cells when present in high copy. The
      screening procedure was based on overproduction-induced mislocalization of acid
      trehalase activity; overproduction of vacuolar enzymes that transit through the
      secretory pathway leads to secretion to the cell surface. A DNA fragment that
      confers cell surface expression of acid trehalase activity was cloned and
      sequenced. The deduced amino acid sequence displayed no homology to known
      proteins, indicating that we have identified a novel gene. A deletion in the
      genomic copy of the ATH1 gene eliminates vacuolar acid trehalase activity. These
      results suggest that ATH1 may be the structural gene encoding vacuolar acid
      trehalase or that the gene product may be essential regulatory component involved
      in control of trehalase activity.

PMID- 7502578
TI  - Improvement of chromosomal DNA extraction from different yeast species by
      analysis of single preparation steps.
AB  - A modified procedure is proposed for chromosomal DNA extraction based on a cell
      wall lytic enzyme never applied before in pulsed field gel electrophoresis.
      Protoplasting efficiency is retained under very challenging conditions for enzyme
      activity, such as those required for non-Saccharomyces yeasts often characterized
      by cell walls highly resistant to lysis.

PMID- 7502579
TI  - Transcriptional regulation by an upstream repression sequence from the yeast
      enolase gene ENO1.
AB  - The activity of an upstream repression sequence (URS element) that mediates a 20
      fold repression of ENO1 expression in cells grown in a medium containing glucose
      was characterized. Sequences that are sufficient for orientation-dependent ENO1
      URS element activity were mapped between positions -241 and -126 relative to the
      ENO1 transcriptional initiation site. The ENO1 URS element repressed
      transcription of the yeast CYC1 gene when positioned between the CYC1 upstream
      activation sequences (UAS elements) and TATAAA boxes. The ENO1 URS element failed
      to repress transcription of the wild-type yeast enolase gene ENO2; however,
      expression of an ENO2 gene lacking one of the ENO2 UAS elements was efficiently
      repressed by the ENO1 URS element, suggesting that the URS element interferes
      with the transcriptional activation by some, but not all, UAS elements. In
      contrast to the ENO1 gene, the ENO1 URS element repressed CYC1 and ENO2
      expression in cells grown on glucose or glycerol plus lactate. Evidence is
      presented that the ENO1 URS element also functions during stationary growth
      phase.

PMID- 7502580
TI  - Identification of peroxisomal membrane ghosts with an epitope-tagged integral
      membrane protein in yeast mutants lacking peroxisomes.
AB  - Many yeast peroxisome biogenesis mutants have been isolated in which peroxisomes
      appear to be completely absent. Introduction of a wild-type copy of the defective
      gene causes the reappearance of peroxisomes, despite the fact that new
      peroxisomes are thought to form only from pre-existing peroxisomes. This apparent
      paradox has been explained for similar human mutant cell lines (from patients
      with Zellweger syndrome) by the discovery of peroxisomal membrane ghosts in the
      mutant cells (Santos, M. J., T. Imanaka, H. Shio, G. M. Small and P. B. Lazarow.
      1988. Science 239, 1536-1538). Introduction of a wild-type gene is thought to
      restore to the ghosts the ability to import matrix proteins, and thus lead to the
      refilling of the peroxisomes. It is vitally important to our understanding of
      peroxisome biogenesis to determine whether the yeast mutants contain ghosts. We
      have solved this problem by introducing an epitope-tagged version of Pas3p, a
      peroxisome integral membrane protein (that is essential for peroxisome
      biogenesis). Nucleotides encoding a nine amino acid HA epitope were added to the
      PAS3 gene immediately before the stop codon. The tagged gene (PAS3HA) was
      inserted in the genome, replacing the wild-type gene at its normal locus. It was
      fully functional (the cells assembled peroxisomes normally and grew on oleic
      acid) but the expression level was too low to detect the protein with monoclonal
      antibody 12CA5. PAS3HA was expressed in greater quantity from an episomal plasmid
      with the CUP1 promoter. The gene product, Pas3pHA, was detected by immunogold
      labelling on the membranes of individual and clustered peroxisomes; the clusters
      appeared as large spots in immunofluorescence. PAS3HA was similarly expressed in
      peroxisome biogenesis mutants peb2 and peb4, which lack morphologically
      recognizable peroxisomes. Gold-labelled membranes were clearly visible in both
      mutants: in peb2 the labelled membrane vesicles were generally much smaller than
      those in peb4, which resembled normal peroxisomes in size.

PMID- 7502581
TI  - Sequence analysis of a 9873 bp fragment of the left arm of yeast chromosome XV
      that contains the ARG8 and CDC33 genes, a putative riboflavin synthase beta chain
      gene, and four new open reading frames.
AB  - The DNA sequence of a 9873 bp fragment located near the left telomere of
      chromosome XV has been determined. Sequence analysis reveals seven open reading
      frames. One is the ARG8 gene coding for N-acetylornithine aminotransferase.
      Another corresponds to CDC33, which codes for the initiation factor 4E or cap
      binding protein. The open reading frame AOE169 can be considered as the putative
      gene for the Saccharomyces cerevisiae riboflavin synthase beta chain, since its
      translation product shows strong homology with four prokaryotic riboflavin
      synthase beta chains.

PMID- 7502582
TI  - Sequence analysis of a 44 kb DNA fragment of yeast chromosome XV including the
      Tyl-H3 retrotransposon, the suf1(+) frameshift suppressor gene for tRNA-Gly, the
      yeast transfer RNA-Thr-1a and a delta element.
AB  - We have sequenced on both strands a 44,019 bp fragment located on the left arm of
      Saccharomyces cerevisiae chromosome XV. The sequenced segment contains 22 open
      reading frames (ORFs) of at least 100 amino acids long, one of which probably
      contains an intron. Six of the 22 ORFs correspond to known proteins: the
      multicopy suppressor of Snf1 protein 1, the two Tyl-H3 transposon proteins TyA
      and TyB, the myo-inositol transporter 2, the transcription factor protein Ino4
      and the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase. Of the 16 remaining
      ORFs, two show highest homologies with the yeast serine/threonine protein kinase
      Ste20 and the human tryptophanyl-tRNA synthetase. Eight ORFs show slight
      similarities with protein sequences described in data banks. DNA sequence
      comparison reveals also the presence of three known sequences: the Tyl-H3
      transposable element, the yeast suf1(+) frameshift suppressor gene for tRNA-Gly
      and the yeast transfer RNA-Thr-1a. A fourth DNA sequence shows striking
      identities with the yeast delta elements.

PMID- 7502583
TI  - Sequencing analysis of a 24.7 kb fragment of yeast chromosome XIV identifies six
      known genes, a new member of the hexose transporter family and ten new open
      reading frames.
AB  - The DNA sequence of a 24.7 kb region covering the left arm of chromosome XIV from
      Saccharomyces cerevisiae was determined. This region contains 17 open reading
      frames (ORFs) which code for proteins of more than 100 amino acids. Five ORFs
      correspond to the KRE1, ATP11, DAL82, RFA2 and MCK1 loci, described previously.
      Two ORFs present high similarity to known proteins: NO345 with the hexose
      transporter family, and NO351 with the yeast chorismate mutase/prephenate
      dehydratase enzyme encoded by PHA2. Six ORFs show limited similarity with known
      proteins or some specific features: NO339 presents 11 potential transmembrane
      domains. NO343, which is internal to NO345, presents a putative signal sequence
      and a potential transmembrane domain. NO348 shows similarity with YCW2, TUP1 and
      SEC13. NO364 reveals a signature for a pyridoxal-phosphate attachment site.
      Finally, NO384 and NO388 present a biased amino acid composition, being rich in
      Asn or Glu/Lys/Arg, respectively. Four other ORFs (NO342, NO376, NO381 and NO397)
      show no similarity to proteins within the databases screened.

PMID- 7502584
TI  - The complete sequence of a 9000 bp fragment of the right arm of Saccharomyces
      cerevisiae chromosome VII contains four previously unknown open reading frames.
AB  - We report the sequence of a 9000 bp fragment from the right arm of Saccharomyces
      cerevisiae chromosome VII. Analysis of the sequence revealed four complete
      previously unknown open reading frames, which were named G7587, G7589, G7591 and
      G7594 following standard rules for provisional nomenclature. Outstanding features
      of some of these proteins were the homology of the putative protein coded by
      G7589 with proteins involved in transcription regulation and the transmembrane
      domains predicted in the putative protein coded by G7591.

PMID- 7502585
TI  - A new essential gene GCR4 located in the upstream region of GCR1.
AB  - A new essential gene of Saccharomyces cerevisiae was found upstream of GCR1. Its
      cloning and sequencing predict a 280 amino acid protein (32,577 Da). The
      predicted protein is fairly hydrophobic, and a search of the database did not
      identify any homologous proteins. A LEU2 disruption at codon 104 was lethal, but
      disruption at codon 221 showed a temperature-sensitive conditional growth
      phenotype. Abnormalities were observed in some glycolytic enzyme levels.

PMID- 7502586
TI  - Sequence analysis of a 78.6 kb segment of the left end of Saccharomyces
      cerevisiae chromosome II.
AB  - We report the sequence analysis of a 78,601 bp DNA segment on the left arm of
      chromosome II of Saccharomyces cerevisiae. This 78.6 kb segment spans the region
      from the start of a subtelomeric Y' element up to the ILS1 gene. It contains 49
      open reading frames (ORFs) with more than 100 amino acids length including 14
      internal and five overlapping ORFs. The gene density, excluding the internal
      ORFs, was calculated as one ORF per 2.2 kb. Eight ORFs (PKC1, TyA, TyB, ATP1,
      ROX3, RPL17a, PET112 and ILS1) correspond to previously characterized genes. ORF
      YBL0718 was identified as CDC27; YBL0706 as TEL1. Four other ORFs show strong
      similarities to already known genes. The gene product of YBL0838 is 60% identical
      to the ribosomal protein RPL32 from rat, mouse and man. YBL0701 encodes a protein
      with significant similarity to the initiation factor eIF2 associated p67
      glycoprotein from rat. Eight ORFs were disrupted and the resulting yeast strains
      analysed with respect to their phenotype.

PMID- 7502587
TI  - [Resection of colorectal liver metastases and adjuvant therapy].

PMID- 7502588
TI  - [Regional adjuvant therapy in colorectal liver metastases: requirements for
      clinical therapy studies from the statistical viewpoint].
AB  - The most important methodical principles of clinical trials in oncology are
      presented and applied to the special field of adjuvant chemotherapy for liver
      metastases in colorectal cancer. The presentation is based on accepted
      biometrical principles in medicine and on our experience in several cancer
      trials. Special regard is given to the German multicenter study of the liver
      metastases working group in the "Deutsche Krebsgesellschaft".

PMID- 7502589
TI  - [Classification and documentation of liver metastases of colorectal carcinomas].
AB  - Today, there is a variety of therapy modalities for patients with liver
      metastases. This therapeutic spectrum has made a more accurate classification of
      liver metastasis necessary. Data concerning therapy have to be documented as well
      as pretherapeutic data and data concerning results of pathologic examination.
      Without a careful documentation a reliable comparison between different therapy
      modalities will be impossible and thus a generally accepted concept of liver
      metastasis therapy cannot be expected. A classification of liver metastasis thus
      required should aid in the planning of treatment, yield an indication of
      prognosis, and assist in the evaluation of the results of treatment.

PMID- 7502590
TI  - [Pharmacology of regional chemotherapy of colorectal liver metastases].
AB  - Regional chemotherapy offers a means to enhance the local efficacy of an
      otherwise ineffective systemic chemotherapy. The regional concentration advantage
      of a drug is proportional to its total body clearance and inversely proportional
      to the blood flow through the organ. Regional infusion of adriamycin, cisplatin,
      methotrexate, and mitomycin C has only a small concentration advantage. Due to
      their high body clearance, the fluorinated pyrimidines floxuridine (FUDR) and 5
      fluorouracil (5-FU) enable a high regional concentration advantage with a factor
      > 50 in comparison to their systemic application. Kinetic studies during isolated
      liver perfusion (ILP) proved that the extraction capacity of the liver is
      saturated at 5-FU concentrations > 10(-4) M. In the closed system of ILP, the
      liver removes 11.2 +/- 1.9 mg 5-FU per minute. During hepatic artery infusion the
      extraction of 5-FU and mitoxantrone is always incomplete. Therefore, we could
      detect considerable amounts of these drugs in the systemic circulation. Our
      investigations of 5-FU show that with higher doses and with high flow rates
      possibly effective and at least in single cases toxic serum levels can be
      obtained even during regional application. In the future, in case of hepatic
      artery infusion for colorectal liver metastases for example, pharmacokinetic
      measurements will enable the adjustment of dose and flow rate of antineoplastic
      drugs to benefit from their regional concentration advantage and from likewise
      effective systemic levels.

PMID- 7502591
TI  - [Results of resection and adjuvant therapy of liver metastases of primary
      colorectal tumors--a review of the literature].
AB  - Natural history of patients with colorectal liver metastases is not significantly
      changed even by curative resection. The majority unfortunately relapse. The
      results of adjuvant treatment after resection were evaluated by analysis of 17
      publications as well as by own data (60 patients). 340 patients were either
      treated by intraarterial (n = 201), systemic (n = 82), intraportal (n = 29) or
      intraperitoneal (n = 28) chemoinfusion (5-Fluorouracil or Floxuridine). An
      alternative approach was the treatment with specific immunotherapy using tumor
      vaccination (n = 35) or monoclonal antibodies (n = 20). Morbidity of adjuvant
      treatment includes local (chemical hepatitis, biliary sclerosis) and systemic
      (diarrhea, stomatitis) side effects. Technical complications could reach a level
      of up to 50% in case of local administration. With exception of 6 studies no
      comparison with a resection only group was performed. Despite postulated increase
      of survival and recurrence free time with historical controls the results of
      current ongoing studies are needed before general use of adjuvant treatment can
      be recommended.

PMID- 7502592
TI  - [Adjuvant therapy of liver metastases: active specific immunotherapy].
AB  - The theoretical basis for Active Specific Immunotherapy (ASI) has been worked out
      during the last 15 years. On this basis an improvement of the quality of the
      tumour vaccine could be achieved. Thus we are able to produce a very pure
      preparation of viable autologous tumour cells needing only small pieces of the
      original tumour. In animal experiments the used NDV (Newcastle-Disease-Virus)
      tumour cell vaccine induced a high antitumour immunity. Side effects of this NDV
      tumour vaccine are rare in contrast to BCG admixed tumour vaccines. Concerning
      the effectiveness of ASI only one randomized clinical study has been published
      [Hoover 17, 18]. The results of our phase 11 study show excellent 2 year survival
      rates using the NDV-tumour vaccine as an adjuvant for colorectal cancer patients:
      Dukes B 100% (95.5%-100%), Dukes C 95.0% (90.1%-99.9%). In future a randomized
      study of adjuvant ASI-treatment for these patients with a comparison to adjuvant
      chemotherapy should be performed. In R0-resected liver metastases a randomized
      study of ASI is ongoing.

PMID- 7502593
TI  - [Regional therapy breast cancer liver metastases].
AB  - The prognosis of patients with metastatic breast cancer in particular with an
      involvement of the liver has to be regarded as rather unfavourable. Up today no
      convincing therapy for patients with breast cancer and liver metastases could be
      found. From 1982 to 1991 42 patients with suspicion on liver metastases of a
      primary breast cancer were laparotomized. At that time 20 patients already had an
      extrahepatic formation of metastases. In contrast to the preexaminations an
      histologically benign liver tumor was intraoperatively verified in 6 patients. In
      the other 36 patients the operation was finished in 9 cases as explorative
      laparotomy (group A) because of extensive intra- and extrahepatic manifestation
      and/or vessel abnormalities. In 19 cases an arterial catheter system with
      subcutaneous port was implanted (group B). Partial liver resection combined with
      intraarterial catheter implantation was performed in 8 patients (group C).
      Postoperatively 27 patients monthly received a regional combined chemotherapy
      (groups B+C); a modified FAM scheme (5-Fluorouracil: 1000 mg/12 h/d/2 d,
      Adriamycin: 20 mg/12 h/d/3 d, Mitomycin C: 10 mg/2 h/d/1 d) was used. Response
      could be documented in 12 out of 17 evaluable patients (70.6%). A median overall
      postoperative survival time of 14.5 months for all patients in case of a proved
      liver metastases was calculated. A prolongation could not be realized, neither in
      patients with partial liver resection with regional therapy (group C) nor in
      patients with an intraarterial chemotherapy (group B). Only in exceptional cases
      a successful regional chemotherapy could influence the course
      favourable.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502594
TI  - [Lymph node excision in stomach cancer--a statistical analysis of survival and
      surgical mortality].
AB  - Between January, 1st, 1980 and December, 31st, 1993 all patients with curative
      removed gastric carcinoma were registered to evaluate the effect of an extended
      lymph node dissection on prognosis and perioperative risk. Therefore an analysis
      of all resected lymphatic nodes in 260 patients could be performed. Referring to
      the depth of tumor infiltration and the extension of the lymph node dissection (<
      10 vs > 10 tumor negative lymph nodes) a significant difference could be found
      only for the pT 2 group. In this group the average survival time could be
      improved from 21 to 62 months (p < 0.018) by extended lymph node dissection,
      without increasing the perioperative morbidity. In our experience the extended
      lymphadenectomy offers a significantly improved survival for patients with non
      invasive gastric cancer without enhanced perioperative risk or mortality.

PMID- 7502595
TI  - [Results of surgical therapy of early stomach cancer].
AB  - Between 1972 and 1993 232 patients with early gastric cancer have been resected
      at the Surgical University Hospital of Mannheim. At the time of surgery 9.9% of
      the patients had lymph node involvement, 2 of them had distant metastases. In
      59.9% of the cases (n = 138) a subtotal distal gastric resection, in 34.1% (n =
      79) a total gastrectomy and in 6.4% (n = 15) a proximal or an atypical resection
      were performed. Following distal resection and total gastrectomy a radical
      lymphadenectomy of the compartments I and II was performed. The hospital
      lethality was 5.2%, the morbidity 18.1%. There were no statistical significant
      differences between the different surgical methods. The cumulative-5-year
      survival rate was 80% without any statistically significant differences between
      the surgical methods and the histological types according to the Japanese
      classification of early gastric cancer.

PMID- 7502596
TI  - [Early and late outcome of gastrectomy de principe].
AB  - Presented is a survey of 10 years experience of "Gastrectomie de principe" in the
      treatment of gastric cancer performed in the Surgical Department of Fulda. 219
      gastrectomies were analysed, all of which were combined with lymphadenectomy of
      compartment I and II. Splenectomy was performed in 91%. 20% of the patients were
      operated with an early cancer, 37% showed no lymph node involvement. The rate of
      complications due to surgery was 13%, in 5.5% of patients we saw an insufficiency
      of the anastomosis, causing lethal outcome in 40% of these cases. The overall
      hospital mortality was 5.5%. Survival rates depended strongly on lymph-node
      involvement. The highest 5-year-survival of nearly 90% was seen in patients with
      an intestinal carcinoma in tumor stage T1 N0 M0, the 5-year-survival of all
      patients with an early cancer was 82%. The overall 5-year-survival was 25%. Total
      gastrectomy as the standard operative procedure shows low mortality, good
      controllability of complications and is to be recommended as a sufficiently safe
      therapeutical concept in patients with gastric cancer.

PMID- 7502597
TI  - [Risk and follow-up after multi-visceral resections including the left side of
      the pancreas].
AB  - Aim of this study was to analyze the operative risk of multivisceral resection
      including the left side of the pancreas. Between September 1 th, 1985 and May 31
      th, 1994 18 multivisceral resections including the left side of the pancreas and
      8 left-sided pancreatic resections were performed at the University Hospital for
      General and Abdominal Surgery, Mainz. Postoperatively 5 of the 18 patients with
      multivisceral resections and 3 of the 8 patients with left-sided pancreatic
      resections developed minor complications (wound infections, pneumonia). One
      insufficiency of an esophagojejunostomy was seen. One patient died after
      gastrectomy and left-sided pancreatic resection due to a pneumonia. In this case
      the operation was performed after substitution of 22 red cell packs under
      emergency conditions because of an infiltration of the splenic artery by a
      lymphoma of the stomach. The best prognosis had patients with neuroendocrine
      tumors. These results show that in case of an elective operation the risk of
      multi-visceral resections including the left side of the pancreas is comparable
      to that of left-sided pancreatic resections alone.

PMID- 7502598
TI  - [Extended partial Kausch-Whipple duodenopancreatectomy by resection of tumor
      infiltrated vascular segments].
AB  - AIM: Vessel infiltration of the portal vein is often considered as
      contraindication for pancreas resection for carcinoma. In this retrospective
      analysis we investigated if an extended Whipple's procedure including vessel
      resection submits the patient to a significantly higher risk. PATIENTS AND
      METHODS: From August 1985 until February 1994 179 Whipple's procedures were
      carried out, in 74 cases for carcinoma of the pancreatic head. In this group 26
      patients were classified as stage I (35.2%), 5 as stage II (6.7%), 38 as stage
      III (51.4%) and one patient as stage IV. In 18 cases a segment of the portal vein
      was resected, in 16 cases reconstructed by end-to-end anastomosis and in two
      cases by implantation of a GoreTex prosthesis. No special anticoagulation was
      applied. RESULTS: There were no anastomosis-related complications such as
      hemorrhage, thrombosis or stenosis. The lethality rate was 1.4% (1/74),
      insufficiencies at the pancreas and bile duct anastomosis occurred in 0% and 1.4%
      (1/74), resp. Patients with segmental vessel resection in stage III had a mean
      survival of 9 months and by 3 years there was no survivor compared to 11.7 months
      and 17% survival after 4 years in stage III without vessel resection. CONCLUSION:
      By performing vessel resection more pancreas tumors than earlier are resectable
      without increased risk. Since the results of oncologic alternative treatment
      modalities are still poor pancreas resection represents at present the best
      option for the patient.

PMID- 7502599
TI  - [Long-term survival after surgical therapy of T4 colorectal carcinomas].
AB  - Between 1972 and 1990, 456 patients with locally advanced colorectal carcinomas
      (tumor stage T4) were operated. In 187 cases the operation was extended by
      multivisceral resection and in 269 patients a conventional resection was
      performed. The rate of curative R0-resections was 74.9% for the extended
      resection group compared to 66.2% for the conventional group. The postoperative
      mortality after extended resection was 4.9% (2.9% conventional resection).
      Analyses of long-term results showed a 5-year survival for all R0-resected cases
      of 52.1% +/- 4.1. Further evaluation of additional lymph-node involvement in T4
      colorectal tumors revealed significant differences in 5-year survival: 64.8%
      T4N0; 27.9% T4N1,2; 9.2% T4N3 for conventional R0-resection and 59.9% T4N0; 23.2%
      T4N1,2; 6.6% T4N3 for extended R0-resection. After curative resection (R0) the
      presence or absence of intraoperative tumor-cell dissemination could be
      identified as a significant prognostic factor. In all cases of T4 colorectal
      carcinomas-especially for N1-3-an adjuvant treatment after conventional or
      extended R0-resection is recommended.

PMID- 7502600
TI  - [Effect of lymph node dissection on prognosis of colon carcinoma].
AB  - Surgical treatment is essential for the prognosis of colon carcinoma. The
      extension of the lymph node excision depends on several factors, as operative
      technique and quality of the histopathological examination. In a retrospective
      analysis of 278 patients who had undergone curative primary resection for colon
      carcinoma the influence of lymph node excision on the prognosis has been proved.
      In the period of the analysis (between 1985 and 1993) the mean number of
      dissected lymph nodes could be increased. This had a strong influence on the
      prognosis. Whereas in early tumor stages and in patients with an extended lymph
      node metastasis no correlation between the quantity of lymph node excision and
      the prognosis could be found, patients with an extended local tumor growth
      without lymph node metastasis (pT3/4 pN0; p < 0.03) and patients with local lymph
      node metastasis (pN1; p < 0.0001) gained from the radical lymphadenectomy.

PMID- 7502601
TI  - Barrels VI: Proceedings of a satellite symposium of the 1994 Society for
      Neuroscience Meeting.

PMID- 7502602
TI  - Evaluation of pain perception after anterior capsulotomy: a case report.
AB  - The medial prefrontal cortex has been implicated in pain perception by recent
      anatomical, physiological, and functional imaging data demonstrating that frontal
      and anterior cingulate cortices receive inputs related to nociception;
      neurosurgical case reports suggest that lesions involving these areas may
      specifically reduce the affective or emotional component of chronic intractable
      pain. We examined this hypothesis more closely by assessing psychophysical
      ratings of (1) warmth, pain intensity, and unpleasantness evoked by phasic
      thermal stimuli, (2) tolerance to tonic cold stimuli, and (3) perceived intensity
      of visual stimuli, both before and after neurosurgical lesions of the fiber
      tracts connecting the frontal lobes to subcortical structures. A 22-year-old
      male, with no history of chronic pain, underwent psychophysical testing 3 days
      before, 5 days after, and 6 months after receiving bilateral lesions of the
      anterior internal capsule (aIC), performed as treatment for obsessive-compulsive
      disorder. In each session, the patient rated the intensity and unpleasantness of
      5-sec cutaneous heat stimuli (39-47 degrees C); pain tolerance was measured by
      means of a cold-pressor test (hand immersion in 1 degrees C water). The patient
      was able to differentially rate the intensities of heat stimuli during both pre-
      and postsurgical testing sessions (p < 0.001). However, he rated heat stimuli as
      less intense 5 days after surgery than during presurgical testing (p < 0.001),
      with significant decreases in both pain intensity (p < 0.005) and unpleasantness
      (p < 0.05). Likewise, the patient described the cold-water immersion as less
      painful following surgery, although his tolerance times were substantially
      shorter than those of the presurgical evaluation. Ratings of visual stimulus
      intensity did not differ across the pre- and postsurgical testing periods,
      suggesting that changes in pain perception were not related to attentional or
      cognitive deficits. Magnetic resonance imaging 5 days following surgery revealed
      bilateral lesions and edema centered in the aIC, with some edema in the left
      frontal lobe. Those 6 months later showed substantially smaller lesions involving
      less than half of the aIC and no edema; pain ratings and cold-water tolerance
      measured at that time indicated a substantial return toward the patient's
      presurgical values. These data suggest that blocking subcortical input to the
      anterior cingulate and frontal cortices reduces both the perceived intensity and
      the unpleasantness of noxious stimuli; reduced cold tolerance times--in the face
      of decreased pain perception--may reflect a disinhibition of cortical control on
      spinal reflexes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7502603
TI  - Immunocytochemical localization of GABAA receptors in rat somatosensory cortex
      and effects of tactile deprivation.
AB  - Immunocytochemical techniques were used to investigate the distribution of gamma
      aminobutyric acidA (GABAA) receptors in the rat primary somatosensory cortex
      (SI). Monoclonal antibody 62-3G1 (de Blas et al., 1988; Victorica et al., 1988),
      which recognizes an epitope common to the beta 2 and beta 3 subunits of the GABAA
      receptor, produces staining of small punctate structures throughout the neuropil,
      and around somata and linear processes in all laminae of SI. Receptor
      immunostaining is relatively intense in upper lamina I and in lamina IV, where
      patches of intense receptor staining are interleaved with narrow zones of
      moderate immunoreactivity. Staining is lightest in lamina Vb, where stained
      puncta appear to be aligned with radially oriented processes, and moderate in the
      remaining laminae. Tangential sections through lamina IV reveal that each large
      cortical barrel encompasses several patches of intense receptor staining that are
      aligned with the corners or edges of individual barrels; interbarrel septa are
      moderately of intense cytochrome oxidase (CO) histochemical staining. A similar
      correspondence is apparent between a complex lattice of dense receptor clustering
      and a plexus of dark CO staining in the cortical trunk representation. Six to
      eight weeks of tactile deprivation produced by simple whisker trimming have no
      visible effect on GABAA receptor distribution. This is the case for rats whose
      whiskers were trimmed only during adulthood and for rats deprived from the day of
      birth until examination 6-8 weeks later. However, electrocautery ablation of
      whisker follicles leads to a marked decline in GABAA receptor immunoreactivity in
      cortical barrels associated with the ablated follicles. Our findings indicate
      that there is reasonable, though not perfect, correspondence between the
      distribution of GABAA receptors and the distribution of GABA-containing neurons
      and terminals in rat SI. These elements are associated with regions of intense
      oxidative metabolic activity revealed by CO staining. The density of GABAA
      receptors is reduced in lamina IV following complete loss of peripheral afferent
      input. However, less severe tactile deprivation, which is known to affect
      cortical neuron responsiveness, produces little or no change in receptor
      distribution.

PMID- 7502604
TI  - Temperature-induced changes in the number of vesicles in the free nerve endings
      of temperature neurons of the snake.
AB  - By observing ultrastructural changes under the electron microscope, we
      illustrated exocytosis and recycling of vesicles in the infrared receptor, a kind
      of free nerve ending in the pit organ of the crotaline snake, Trimeresurus
      flavoviridis. While maintaining the snake pit organs at stable temperatures of 15
      degrees C, 25 degrees C, and 30 degrees C, we fixed them by perfusion and then
      processed them for transmission electron microscopy. The largest number of clear
      and coated vesicles appeared in the terminals at the lowest temperature. The
      perimeter and area of a terminal were enlarged at 30 degrees C, and "opening
      waves" on the plasma were prominently found at the highest temperature. We also
      observed coated vesicles that budded from the plasma membrane in the terminals.
      The configuration of mitochondria in the terminals was quantitatively different
      between lower and higher temperatures. The data suggest that exocytosis and
      endocytosis in these terminals operate in a manner similar to that observed in
      other cell types.

PMID- 7502605
TI  - Induction of fos-like immunoreactivity by electrocutaneous stimulation of the rat
      hindpaw.
AB  - Stimulation of peripheral nerves activates the proto-oncogene c-fos, which in
      turn generates its gene product, Fos. Fos and Fos-like proteins are produced in
      the central nervous system in response to chemical, mechanical, thermal, and
      electrical manipulation. The present study demonstrated a relationship between
      the number of Fos-like-immunoreactive nuclei in the spinal dorsal horn and graded
      intensities of electrical stimulation applied to the hindpaws of anesthetized and
      unanesthetized rats. Stimulation levels within the range of 0.1 to 1.0 mA were
      chosen on the basis of parmeters previously determined in behavioral
      investigations of escape reactions. Focal stimulation at these intensities
      activates peripheral axons directly, but does not injure or traumatize peripheral
      tissues. There was no evidence of inflammation or edema as a result of the focal
      electrical stimulation. As the stimulation intensity increased, the number and
      distribution of Fos-like-labeled nuclei increased with respect to rostral-caudal
      and laminar orientation. The threshold for expression of Fos-like
      immunoreactivity was different for anesthetized and unanesthetized animals. For
      anesthetized animals, the number of labeled nuclei increased significantly from
      the control level only when 1.0 mA was applied. However, in unanesthetized
      animals, the pattern of labeling was statistically significant at 0.2 mA. The
      present study demonstrates that electrical stimulation can evoke the expression
      of Fos-like immunoreactivity by activating nociceptors in the absence of tissue
      injury, and that the use of anesthetics can modulate this expression.

PMID- 7502606
TI  - Effects of anterolateral spinal lesions on escape responses of rats to hindpaw
      stimulation.
AB  - In order to determine the effects of spinal cord lesions on nociceptive
      sensitivity of rodents, methods were developed to assess the speed of operant
      escape responses to electrocutaneous stimulation (ES). ES was delivered across
      the dorsal and ventral surfaces of either hindpaw, producing a current path
      through deep tissues. In order to guide establishment of a range of stimulus
      intensities for this manner of stimulation, a preliminary human psychophysical
      experiment was conducted with stimulation between the dorsal and ventral surfaces
      of a finger. For the human subjects, detection thresholds averaged 0.13 mA, and
      thresholds for a sharp (but nonpainful) sensation were 0.42 mA. Levels of
      stimulation between these thresholds for detection and a sharp quality elicited
      sensations of tingle or itch. Thresholds for reports of pain averaged 0.67 mA. On
      the basis of these results, intensities of ES ranging from 0.05 to 1.0 mA were
      presented to the feet of rats that were trained to perform an escape response
      with one forelimb. Thresholds for escape averaged slightly less than 0.1 mA;
      responding was consistent at 0.4 mA; and response probability and speed were
      maximal at approximately 0.8 mA. Thus, the rats responded aversively at
      intensities below those rated as sharp or painful by the human subjects, but the
      speed of escape reached a plateau at intensities that were above pain threshold
      for the human subjects. Unilateral thoracic lesions of the lateral spinal column
      of rats produced a contralateral hypalgesia. Escape thresholds were elevated, and
      the speed of escape responses to all intensities was reduced. This effect
      depended upon interruption of axons in the middle and anterior portions of one
      lateral column, corresponding to the location of long ascending pathways for
      nociception, including the spinothalamic tract. The speed of escape responding
      increased over 20 weeks of postoperative testing of animals with the largest
      lesions. This confirms results obtained previously from monkeys (by means of a
      similar paradigm), and corresponds to clinical reports of humans who have
      received spinal lesions for control of intractable pain. Thus, the location and
      organization of nociceptive pathways in the spinal cord of rodents appear to be
      similar to those of primates, and similar adaptations occur following
      interruption of these pathways.

PMID- 7502607
TI  - Effects of cross-modal manipulations of attention on the ability of human
      subjects to discriminate changes in texture.
AB  - Cross-modal manipulations of attention significantly affect the detectability of
      tactile stimuli, but the effects on a more complex perceptual task, the
      discrimination of surface texture, are unknown. This study sought to examine
      whether attention influences the ability to discriminate a change in texture
      during passive touch. Twelve subjects were trained to perform two discrimination
      tasks: discriminating an increase in the intensity of a visual stimulus, and
      discriminating a change in the texture of a surface that was displaced beneath
      the tip of one digit. The texture change consisted of an increase in the spatial
      period between rectangular arrays of raised dots on Nyloprint surfaces, and for
      each subject an increment close to his or her discrimination threshold was
      employed in the experiment. Each trial began with the presentation of two
      baseline stimuli: A standard voltage illuminated the visual stimulus (an array of
      yellow light-emitting diodes (LEDs), and a standard texture (3-mm spatial period)
      was displaced under the tip of digit 3. For visual trials, three different
      increments in luminous intensity were presented, at one of three different delays
      following the initial presentation of the baseline stimuli. For texture trials, a
      single increment in spatial period was presented at one of three delays after the
      onset of the baseline stimuli. In any one trial, only one modality changed in
      intensity. The subject's task was to signal, as quickly as possible, the
      occurrence of the change. Instructional cues (red and green LEDs) were used to
      direct the subjects' attention toward the modality that changed (valid cue), to
      divide the subjects' attention between the visual and tactile modalities (neutral
      cue) as either might change, or to direct the subjects' attention toward the
      modality that did not change (invalid cue). Two measures of performance were
      employed: accuracy (percentage correct) and reaction time (speed with which the
      subject responded). The results indicated that cue condition significantly
      influenced the ability of subjects to discriminate a change in texture: Both
      accuracy and speed were significantly improved when subjects' attention was
      selectively directed toward the textured surface, as compared to when it was
      misdirected toward the visual modality. Performance was intermediate when
      attention was divided between the two modalities. The results were compared with
      those obtained previously in a tactile detection task using a similar attentional
      manipulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7502608
TI  - [The current role of surgery in renal calculi].
AB  - We report our experience on 63 patients submitted to kidney stone surgery,
      between january '88 and june '94, at the Division of Urology, in Parma (Italy).
      Nowadays percutaneous lithotripsy (PCNL) and extracorporeal shock wave
      lithotripsy (ESWL) permit the resolution of lithiasic disease in more than 90% of
      the cases; in fact, the incidence of open surgery in only about 1-12%. At the
      present, the role of traditional surgery is also directed to resolution of
      damages of endourological and extracorporeal failures, as post-traumatic events.
      We want to emphasize, as now, that essential surgical approach to kidney surgery
      is lacking in the aim of young urologists training.

PMID- 7502609
TI  - [Percutaneous nephrolithotripsy (PCNL). The authors' own experience with 106
      patients].
AB  - The authors report 106 consecutive patients who underwent percutaneous removal or
      debulking of renal stones from March '88 to June '94. Removal was successful in
      64 pts (60%), while 6 patients (5.6%) needed a second-look section and in one
      case (0.9%) a third-look; in 33 cases (31.3%) PCNL was performed as debulking
      procedure before ESWL. The major complications were: 1 severe haemorrhage with
      secondary nephrectomy, 2 respiratory complications, 1 intestinal fistula, 2
      hyponatremic syndromes, 1 global kidney functional exclusion and 1 sectorial
      exclusion. PCNL is an effective technique to treat the majority of single big
      renal stone or debulking procedure in staghorn calculi before ESWL.

PMID- 7502610
TI  - [Laparoscopic splenectomy: comments on the surgical technic].
AB  - The authors describe the technique applied in their first case of laparoscopic
      splenectomy, in a patient with idiopathic thrombocytopenic purpura. Different
      technical approaches adopted by other surgeons are referred and discussed. The
      laparoscopic approach to splenectomy seems safe and allows the patients to re
      return to normal activity sooner than the "open" technique. Laparoscopy should be
      considered in patients who require splenectomy for benign disease.

PMID- 7502611
TI  - [The prognostic evaluation of acute pancreatitis].
AB  - Early identification of severity is one of the most important problems in acute
      pancreatitis, both for decision-making and classification. Predictive criteria
      show a wide range of accuracy: clinical examination (on admission: 76-85%);
      single laboratory data (PCR: 68-98%, C3-C4: 63-72%); multifactorial scoring
      systems (Ranson: 65-82%, Imrie: 78-95%); diagnostic peritoneal lavage (72-90%);
      CT features (52-81%). In 1982 we started a prospective evaluation of the
      prognostic performances of a bayesian statistical model for the prediction of
      severe vs mild pancreatis and death vs survival, which uses the outcome-related
      patterns of several variables, assuming their independence, analysed on a data of
      44 patients. The performances have been calculated prospectively by comparing the
      expected vs actual results on 88 further patients (accuracy, sensitivity and
      specificity, respectively, in the prediction of severe pancreatitis: 92%, 92%,
      93%; in the prediction of death: 95%, 97%, 87%). Moreover, the model can
      represent classes of risk by combining prediction of death + severe pancreatitis
      (DSP), survival + severe pancreatitis (SSP) and survival + mild pancreatitis
      (SMP) (accuracy, sensitivity and specificity, respectively, in the prediction of
      DSP: 97%, 83%, 100%; in the prediction of SSP: 95%, 87%, 97%; in the prediction
      of SMP: 95%, 97%, 90%). Our model enables clinicians dealing with other
      population to re-determine different variables or integrate them with new
      information, whenever available. It seems to be transferable and adaptable, even
      with a probable further increase of the performances, without compromising the
      objectivity of the predictive judgement and the homogeneity of the classes of
      risk.

PMID- 7502612
TI  - [The time parameters of the stapedius reflex. The normal results].
AB  - The evaluation of the temporal characteristics of the acoustic stapedius reflex
      is one the fundamental aspects of the impedance audiometry, since significant
      biological information to be used as sensitive indicators of distinctive
      pathologies can be obtained. At the Audiology Service of the E.N.T. Department of
      Parma four parameters of the acoustic stapedius reflex have been studied (onset
      latency, latency at 10% of the maximum amplitude, rise time, offset latency) in a
      group of people having normal ears without previous otological problems, with the
      aim to establishing some rules. The equipment used is the Madsen Impedenzometro
      ZO 174 which enables to obtain an average among a desired number of reflex
      responses. The report shows the value of the four parameters of the stapedius
      reflex obtained from the study of 10 normoacusic patients totalling 20 ears. The
      resulting guidelines can make up the basis for further research in pathological
      cases with cochlear, neural and central lesions.

PMID- 7502613
TI  - [Extracorporeal shockwave lithotripsy (ESWL). Our experience].
AB  - The authors report their experience with a third generation lithotripter Storz
      Modulith SL 20 with fluoroscopic and echography stone localization. A total of
      284 patients, between september '92 and august '94, with 149 renal and 135
      ureteral stones, underwent 483 treatments. The mean treatment rate was 1,7 and
      the over-all stone free rate was 93%. Auxiliary procedures before ESWL were
      performed in 5.1% of the sessions (stenting, nephrostomy tube) and in 1% post
      ESWL manipulations for lithiasic steinstrasse. Complications as: renal damage,
      steinstrasse etc. occurred in 2.5% of the session; in 20 patients ESWL procedure
      failed.

PMID- 7502614
TI  - [Unilateral pulmonary embolectomy without extracorporeal circulation. A report of
      a clinical case].
AB  - The surgical treatment of pulmonary embolectomy is currently indicated for acute
      massive obstruction of the pulmonary artery with severe haemodynamic failure and,
      as in this case, when medical treatment with anticoagulants or thrombolytic drugs
      is contraindicated. In this work, the Authors focus on the technique of
      unilateral pulmonary embolectomy through a median sternotomy; this approach
      allowed an easier and safer embolectomy without extracorporeal circulation.

PMID- 7502615
TI  - [Spontaneous intracerebral hemorrhage: case histories].
AB  - Spontaneous intracerebral hemorrhage is a significant cause of morbidity and
      mortality. The disease primarily affects men between the age of 45 to 75 years.
      Arterial hypertension is the most frequent etiologic factor. Here is presented a
      case-record of 148 intracerebral hemorrhages observed during a five years period.
      Several clinical and radiological features have been correlated and analyzed from
      a statistical point of view. The most important prognostic factor is the state of
      consciousness. Either deep coma and a normal state of consciousness do not
      represent surgical indications.

PMID- 7502616
TI  - Cost-effectiveness in surgery. The insurers' point of view.
AB  - Cost-effectiveness in surgery is only one example of a global health care policy
      by the Belgian social insurers aiming at optimal price-quality ratios for the
      offered care provision and within budgetary constraints. As a main partner in
      health care management the insurers' decision is guided by socio-economical
      evaluation of medical technology and care. This evaluation distinguishes
      respectively cost-benefit (CBA), cost-effectiveness (CEA) and cost-utility (CUA)
      analyses. In surgery the principles of cost-effective management are illustrated
      with examples for minor surgery in general practice, one day clinic, tympanostomy
      tube placement for recurrent otitis media, and laparoscopic vs. laparotomic
      cholecystectomy. Even if we need economic evaluation for policy making it can
      only be one instrument for making choices in the increasingly complex and
      expensive health care sector. To maintain the access, the quality and the
      actually fair cost-level in Belgium's compulsory health insurance system there is
      need for standardized indications, clinical guidelines, outcome evaluation and
      quality assurance by credentialing of providers and service centers.

PMID- 7502617
TI  - Cost-efficient management in surgery. The view of the hospital administrator.
AB  - The views of hospital administrators, doctors and payers on cost-efficiency in
      surgery do not necessarily coincide. The difference between charges and cost and
      the particularities of the financing mechanisms may induce situations in which
      savings for the society as a whole result in financial loss for the hospital.
      Examples are in the use of stapling devices, in ambulatory surgery, in endoscopic
      surgery: they all result in better quality of care and decreasing health care
      cost for society; they often induce, however, a not compensated increase in
      hospital costs. Surgeons and administrators can find each other in a common
      concern for optimizing efficiency. This asks for an agreement regarding the
      techniques and equipment to be used, and regarding the necessary minimum case
      load. This paper presents the case of the endoscopic cholecystectomy as an
      example. The second part of the paper deals with various aspects of quality and
      cost of the hospital product. It warns against purely technology-inspired
      investments which entail a risk for overconsumption and inappropriate use. It
      also asks for attention for the educational cost and for the continuing running
      cost which may result from capital investment decisions. Finally it underscores
      the role that surgeons can play in reducing the running cost, by paying attention
      to a smoother organisation of the OR activities and to the choice of materials,
      consumables and pharmaceuticals.

PMID- 7502618
TI  - Bronchioloalveolar carcinoma: long-term survival of 23 resected patients.
AB  - We studied 23 patients, who underwent resection for bronchioloalveolar carcinoma
      between 1975 and 1992. The predictive value of the radiologic features, TNM
      staging, histopathologic type and extent of resection were examined. There were
      20 men and 3 women (13%) with a mean age of 58 years (32-72y). Of all patients,
      18 (78.3%) were asymptomatic. At chest X-ray, 14 (61%) revealed a solitary
      nodule, 6 an infiltrative or pneumonic mass, one a cystic lesion, and two
      multinodular lesions. The actuarial five-year survival was 46 +/- 23%. When a
      lobectomy was performed for bronchioloalveolar carcinoma, survival was better
      than when a pneumonectomy was performed. None of the seven patients who underwent
      a pneumonectomy survived 5 years. The actuarial 5-year survival of the 16
      lobectomies was 70 +/- 25%. There was no statistical difference in survival
      between the histopathologic types.

PMID- 7502619
TI  - Emergency aorto-iliac aneurysm surgery with low mortality and morbidity.
AB  - The authors present a consecutive series of 27 patients (26 men, one woman),
      urgently operated for aortic or iliac aneurysm during the period 1986-1994. Mean
      age was 68 years. Free rupture was found in 16 cases, 8 times a rupture with
      important retroperitoneal haematoma and fissurisation in 4. There were three
      ruptures of iliac aneurysms. In two cases arterio-venous fistulisation occurred:
      one ilio-iliac, another aorto-caval. For two juxta-renal aneurysms, supra-renal
      crossclamping was necessary and nephroplegia was used. Every reconstruction was
      done by Dacron prosthesis: a straight tube (47%), an aortobi-iliac (15%) or an
      aorto-bifemoral bifurcation prosthesis (38%). Mortality was 19% (0.0654 to 0.315,
      90% confidence limits) with one intra-operative death. The morbidity was 49%,
      mostly by respiratory and/or renal complications, and mainly transient in nature.

PMID- 7502620
TI  - Strangulation: a late presentation of right-sided diaphragmatic rupture.
AB  - A case of late presentation of a right-sided diaphragmatic rupture due to blunt
      chest trauma is presented. The patient suffered from strangulation of a herniated
      segment of small bowel into the chest. Chest radiography suggested diaphragmatic
      rupture, computed tomography and sonography established the correct preoperative
      diagnosis. The prevalence, mechanism of injury and possible complications are
      reviewed. The value of chest radiography and other imaging techniques is
      discussed.

PMID- 7502621
TI  - Radial club hand and Holt-Oram syndrome.
AB  - The authors describe the case of a young African girl born with a radial club
      hand associated with a pedicled floating thumb, no other orthopaedic malformation
      was detected. A ventricular septal defect necessitated surgery in emergency. In
      front of such malformative association, the Holt-Oram syndrome has been evoked.
      The aim of this study has been to review the etiology and classification of this
      rather rare malformative association, as well as to describe the therapeutic
      attitudes and surgical techniques proposed by various authors towards the radial
      club hand (1, 3, 5, 6, 7, 12).

PMID- 7502622
TI  - Insertion of an aortic and pulmonary homograft for simultaneous reconstruction of
      the left and right ventricular outflow tracts. A case report.
AB  - We present the case of the successful reconstruction in a child of a congenital
      cardiac malformation (tetralogy of Fallot) complicated by acquired aortic
      regurgitation and aneurysm formation of the left pulmonary artery due to previous
      endocarditis, by using an aortic homograft for reconstruction of the left
      ventricular outflow tract and a pulmonary homograft for reconstruction of the
      right ventricular outflow tract. Regarding the excellent results recently
      obtained with cryopreserved homografts, the many advantages of these valves
      compared to mechanical prostheses, we feel that aortic and or pulmonary
      homografts might constitute ideal biological valves for reconstruction of left
      and or right ventricular outflow tract in children when the presence of a
      congenital anomaly of the pulmonary valve renders an autograft impossible.

PMID- 7502623
TI  - The persistent sciatic artery. A case report.
AB  - We describe a case of a complete persistent sciatic artery in an asymptomatic
      patient with multiple aortoiliac aneurysms. After endoaneurysmorraphy and
      ligation of the persistent sciatic artery at its origin, the patient did well,
      without ischaemic complications. Peripheral vascular reconstruction, although
      often recommended in the literature, did not seem to be indicated in this case.

PMID- 7502624
TI  - Growth of tracheal sutures with absorbable sutures in primates.
AB  - Postoperative wound healing is studied after tracheal suturing in 5 primates
      operated on in two stages. First by double level hemisection comparing continuous
      and interrupted sutures with polydioxanone. In a second stage: comparison of
      continuous sutures after tracheal segmental resection. The tracheas were
      harvested sequentially to study the evolution of the sutured zone by measuring
      its diameter and by histopathologic examination. The reduction of the tracheal
      diameter observed was not statistically significant after hemisection using
      continuous (p = 0.7) or interrupted sutures (p = 0.6). But after tracheal
      resection the stenosis was significant with continuous sutures (p < 0.05).
      Histologic study revealed that polydioxanone is well tolerated and is absorbed
      within 26 weeks. The authors recommend the use of continuous sutures to repair
      simple wounds and of interrupted sutures after tracheal resection anastomosis.

PMID- 7502625
TI  - Radiation induced carotid artery blowout.

PMID- 7502626
TI  - Circulating erythropoietin in patients with acquired aplastic anaemia.
AB  - The plasma erythropoietin (Epo) concentration was measured by radioimmunoassay in
      75 patients with acquired aplastic anaemia. Overall there was an inverse
      relationship between the concentration of plasma Epo and the degree of anaemia.
      Plasma Epo concentrations were lower in patients who were sampled soon after
      diagnosis as opposed to those studied at later times. Although a decrease in the
      plasma Epo concentration was noted in all erythroid responders following
      immunosuppressive (IS) therapy or bone marrow transplantation (BMT), it was lower
      in patients undergoing BMT than in those receiving IS therapy for any given
      degree of anaemia.

PMID- 7502627
TI  - Splenic function in acute leukemia.
AB  - Spleen function was evaluated in 36 patients with acute leukemia by enumeration
      of pitted erythrocytes and analysis of clearance from circulation of heat-damaged
      99mTc-labelled erythrocytes (HDE). At diagnosis, the mean percentage of pitted
      erythrocytes was significantly higher in the patient group (4.04 +/- 7.19%) than
      in the control group (0.41 +/- 0.35%; p < 0.01), suggesting the occurrence of a
      splenic hypofunction in a high proportion of the patients. Accordingly, the
      clearance of HDE showed a pattern of splenic hypofunction in 4 out of 7 patients,
      based on reduced values for the parameters C20 (overall clearing function of the
      spleen), K (the rate constant of HDE irreversibly trapped) and K/K1 + K (the
      fraction of HDE entering the spleen undergoing permanent removal). After
      successful treatment, the pit counts decreased in all reassessed patients,
      returning to normal values in 10 out of 12 patients with high pit counts at
      diagnosis. Additionally, two patients with normal pit counts at diagnosis
      presented borderline results for the parameters C20 and K, which may suggest a
      slight splenic hyperactivity in these patients. These results demonstrate, for
      the first time, the presence of functional spleen abnormalities in patients with
      acute leukemia.

PMID- 7502628
TI  - On the use of hydroxyurea/erythropoietin combination therapy for sickle cell
      disease.
AB  - Seven sickle cell disease (SCD) patients [sickle cell anaemia = 4 (males 2,
      females 2, age range 18-40 years), and sickle cell beta (0)-thalassaemia = 3 (all
      females, age range 20-47 years)], suffering from a severe form of the disease
      were enrolled in a treatment protocol using hydroxyurea (HU) for up to 12 months
      followed by a combination therapy with HU and human recombinant erythropoietin
      (rHuEpo; using 400 U/kg/week i.v.) for 3-4 weeks. Following the withdrawal of
      rHuEpo the patients were maintained on HU alone. The patients were characterised
      on the basis of the 'severity index' prior to the initiation of the therapy.
      Haematological and relevant biochemical parameters, Hb A2 fetal haemoglobin
      (HbF), HbF cells, reticulocytes and platelet counts were estimated at least at
      three occasions to determine the mean and range of the parameters. During the
      treatment period the patients were followed every 2-4 weeks where the
      haematological and biochemical parameters were assessed. The results were
      separately analysed and mean +/- SD were obtained for each parameter at the end
      of each protocol. The statistical significance of the difference in the results
      obtained on treatment and the baseline results was examined using the paired t
      test. No toxic side effects of HU and rHuEpo (as judged from reduction in
      platelet and white blood cell count) were documented during and after the whole
      period of treatment. The patients showed a significant clinical improvement.
      Total haemoglobin, haematocrit, red cell count, HbF and HbF cells increased,
      while white blood cells, reticulocyte counts and bilirubin level decreased.
      Platelet count decreased but remained within the normal range. The results
      revealed that 5 of the patients on HU treatment showed a significant increase in
      the HbF level and HbF cells, while 2 patients (1 sickle cell anaemia and 1 Hb
      S/beta(0)-thalassaemia patient) did not and were considered as 'non-responders'.
      The rHuEpo and HU combination therapy elevated the HbF level, with a varying
      degree, in all patients except 2, who had already reached a high HbF level and
      showed a decrease in HbF during the rHuEpo protocol. Variable individual response
      to both HU and rHuEpo therapy was a common feature. We recommend the use of HU
      for the treatment of SCD and a combination therapy using HU and rHuEpo for the
      non-responders.

PMID- 7502629
TI  - Tuberculosis presenting as immune thrombocytopenic purpura.
AB  - Various haematological abnormalities commonly occur in active tuberculosis (TB).
      However, thrombocytopenia is rare and immune thrombocytopenic purpura (ITP) is
      mentioned only in few case reports. We found that of 846 cases with active TB, 9
      (1%) presented with ITP as the only abnormality. Three out of these 9 cases had
      disseminated miliary TB, 3 an abdominal abscess or lymphadenitis, and 3 pulmonary
      TB; none had palpable splenomegaly. All patients had purpura and the platelet
      count varied between 4 and 21 x 10(9)/l, and the bone marrow showed increased
      megakaryocytes. All tuberculous patients showed initially a poor platelet count
      response to steroid therapy. The platelet count returned to normal 2-6 weeks
      after oral prednisone combined with antituberculous drugs.

PMID- 7502630
TI  - Detection of minimal residual disease in a patient with acute myeloid leukemia
      and t(6;9) at the time of peripheral blood stem cell transplantation.
AB  - A 16-year-old Japanese woman with acute myelogenous leukemia (AML) and t(6;9)
      received peripheral blood stem cell transplantation (PBSCT). Although chromosomal
      studies just prior to and following PBSCT showed a normal karyotype, reverse
      transcription-polymerase chain reaction (RT-PCR) detected the mRNA derived from
      the dek-can fusion gene of t(6;9) following PBSCT and in the harvested stem
      cells. Following PBSCT, she relapsed. To our knowledge, this case is the first
      report from Japan in which minimal residual disease was detected with RT-PCR in
      AML with t(6;9). These methods should improve the use and outcome of PBSCT.

PMID- 7502631
TI  - Acute nonlymphocytic leukemia complicated by Garcin's syndrome.
AB  - A 15-year-old girl was diagnosed as having acute nonlymphocytic leukemia (ANLL,
      FAB M2) in January 1990 and achieved complete remission with chemotherapy. She
      was readmitted to our hospital with a hearing disturbance and hoarseness in
      October 1990. A suprapharyngeal tumor was found on cranial MRI, and bone marrow
      leukemic cells were slightly increased in number. Involvement of leukemic cells
      was proven by biopsy of the tumor. Therefore, we made a diagnosis of ANLL relapse
      with Garcin's syndrome. To our knowledge, this is the first reported case of
      leukemia complicated by Garcin's syndrome.

PMID- 7502632
TI  - Identification of several alpha-globin gene variations in a small Laotian family.
AB  - The present study concerns the identification of four alpha-globin gene
      deficiencies, one alpha 1-globin gene mutation, and one beta-globin gene mutation
      in a Laotian couple and their newborn baby. The parents were Hb E heterozygotes
      and the baby was an Hb E homozygote. The father carried the 4.2-kb deletion on
      one chromosome and a TAA-->CAA mutation at the terminating codon of the alpha 2
      gene (Hb Constant Spring or CS) on the other chromosome. Moreover, the remaining
      alpha 1-globin gene on the chromosome with the 4.2-kb deletion was mutated at
      codon 74 (GAC-->CAC; Asp-->His; Hb Q-Thailand). The mother had the 3.7-kb
      deletion on one chromosome and a TAA-->TAT mutation at the terminating codon of
      the alpha 2-globin gene (Hb Pakse) of the second chromosome. The baby was a
      compound heterozygote for the two termination codon mutations and, at birth, had
      a high level of Hb Bart's (16.6%) reflecting a mild form of Hb H disease.

PMID- 7502633
TI  - Diagnosis of disseminated candidiasis by fine needle aspiration of lymph node and
      by splenic imprint in a patient with acute promyelocytic leukemia.
AB  - Cytologic studies were done on fine needle aspirates of the lymph node and
      imprints of splenic biopsies from a patient with acute promyelocytic leukemia who
      was febrile while being treated with chemotherapy. Examination of the lymph node
      aspirates revealed pus and numerous pseudohyphae which were later identified as
      Candida tropicalis. When multiple nodular lesions were detected in the spleen by
      abdominal sonography and CT scan, needle biopsy of the spleen was done. Cytologic
      examination of touch imprints of the biopsy disclosed intracellular fungal
      blastospores. The patient was treated with and responded well to amphotericin B
      and 5-fluorocytosine. As a result of our experience with this patient we
      emphasize the importance of close incorporation of clinical information and
      diagnostic cytology. With such a cooperation, cytologic studies become a most
      useful method for diagnosis.

PMID- 7502634
TI  - Characterization of chromosome 11 with a complex inversion and deletion in an AML
      [M2] using fluorescence in situ hybridization.
AB  - We report on a new case of AML [M2] where chromosome 11 was rearranged in a
      highly complex manner involving band 11q23. Routine G banding failed to identify
      the nature of this aberration which later was accomplished using whole chromosome
      11-specific painting probe by the FISH technique. Chromosome 11 band q23 is
      frequently involved in reciprocal translocations with various chromosomes, but to
      have sole morbidity of such a complex nature is an atypical finding in AML [M2].
      The band q23 of chromosome 11 involves the mixed lineage leukemia gene and
      rearrangement of this chromosomal region has been found in a variety of
      neoplasias. Henceforth, its precise identification has become imperative for
      classification of hematological malignancies and in turn to devise therapeutic
      strategies.

PMID- 7502635
TI  - Primary adrenal lymphoma with chromosomal abnormalities.
AB  - Lymphomas developing in the adrenal glands are rare. Twenty-one cases of primary
      adrenal lymphomas have been reported in the English literature, but no
      cytogenetic data were given. We had the opportunity to examine three cases of
      primary adrenal lymphoma characterized by the B cell phenotype. Samples for
      histologic and immunohistologic diagnosis were obtained from postmortem
      examination in cases 1 and 2, and with an ultrasound-guided needle biopsy in
      cases 2 and 3. In all 3 cases, histologic examination of adrenal masses showed
      diffuse medium-sized cleaved lymphoma cells, which were positive for L-26, an
      immunohistochemical B cell marker. Endocrine studies showed adrenal insufficiency
      in 1 case. Cytogenetic examination showed clonal abnormalities, including 8q24 in
      case 1 and 14q32 in case 2, similar to those observed in nodal B cell lymphoma.

PMID- 7502636
TI  - Role of Pneumocystis carinii DNA amplification by PCR on the diagnosis of
      Pneumocystis carinii pneumonia in patients with haematologic malignant diseases:
      report of four cases.

PMID- 7502637
TI  - Increased immunoglobulin E and interferon-gamma in patients with malignant
      lymphoma.

PMID- 7502638
TI  - Human herpesvirus-6 genome in acute lymphoblastic leukemia: evidence against an
      etiologic relationship.

PMID- 7502639
TI  - The disruptive physician.

PMID- 7502640
TI  - Political action committees: an overview.

PMID- 7502641
TI  - Nurse anesthetists remembering a world at war--Part I: Nurse anesthetists prepare
      for war, 1939-1941.

PMID- 7502642
TI  - AANA journal course: update for nurse anesthetists--pulmonary aspiration
      revisited: changing attitudes toward preoperative fasting.
AB  - Pulmonary aspiration during anesthesia, although rare in most patients, remains a
      very real concern for anesthesia providers. Recently, an extensive collection of
      data has emerged demonstrating a seemingly benign effect of gastric pH and volume
      from clear liquids consumed 2 to 3 hours prior to surgery in select patients.
      This AANA Journal course will evaluate the risk of pulmonary aspiration and
      relate this to specific identifying characteristics described to influence risk.
      Gastric physiology will be reviewed and current research will be examined
      evaluating the impact of clear liquids on specific outcome variables.

PMID- 7502643
TI  - Anesthetic management of the cocaine abuse patient.
AB  - Cocaine is an extremely addictive local anesthetic which can produce stimulation
      of the sympathetic nervous system due to the inhibition of catecholamine reuptake
      at the synaptic junction. Because of the rapid metabolism of cocaine, the
      probability of a patient presenting to the operating room with acute intoxication
      is unlikely. However, the physiological effects of chronic cocaine abuse on
      various organ systems have an impact on anesthesia management. A preoperative
      review of major organ systems is essential. Selective beta 1 antagonists (i.e.,
      esmolol) may need to be titrated with a direct vasodilator (i.e., nitroprusside)
      to manage hypertension and tachycardia. The nonselective beta antagonist effects
      of labetalol are much more potent than its alpha antagonist effects, which could
      result in unopposed alpha vasoconstriction. In addition, the equal affinity of
      the alpha adrenergic antagonist, phentolamine, for both alpha 1 and alpha 2
      receptors may result in significant tachycardia. Nitroglycerin has also been used
      in management of hypertension associated with coronary vasoconstriction. There is
      controversy regarding management of ventricular dysrhythmias and asystole.
      Lidocaine is an amide local anesthetic that may have addictive effects, in the
      presence of cocaine, which may lower the seizure threshold. In addition, the use
      of epinephrine to treat asystole is controversial in the presence of a state of
      excess catecholamines induced by cocaine. General anesthesia may include
      barbiturates, nitrous oxide, and opioids. Inhalational agents may be used with
      caution due to their myocardial depressant effects. Regional anesthesia may be a
      good choice if coagulopathies and hypovolemia are corrected before the procedure.

PMID- 7502644
TI  - Laryngeal mask airway: an alternative for the difficult airway.
AB  - The laryngeal mask airway (LMA) was invented by Dr. Archie Brain at the London
      Hospital, Whitechapel, in 1981. Dr. Brain's main objective for the LMA was that
      it would provide a better method of maintaining a patient's airway than by face
      mask. Also, the LMA would be less hemodynamically stressful than with insertion
      of an endotracheal tube. The LMA consists of a silicone rubber tube connected to
      a miniature silicone mask. The perimeter of the mask consists of an inflatable
      elliptical cuff, which forms a tip at the distal aspect of the LMA. The aperture
      bars in the dome of the mask lift the epiglottis away, so the lumen remains
      unobstructive. The LMA forms a low pressure seal around the larynx. The LMA is
      contraindicated in any situation where the patient is at risk for pulmonary
      aspiration. The LMA is not a substitute for a properly placed endotracheal tube
      in this situation. The American Society of Anesthesiologists' difficult airway
      algorithm recommends the insertion of an LMA when ventilation and/or intubation
      are difficult. The distal aperture of the LMA is in close approximation to the
      vocal cords, so a 6.0-mm internal diameter endotracheal tube can be passed over
      an intubating stylet or a pediatric fiberoptic bronchoscope to secure a patient's
      airway.

PMID- 7502645
TI  - General anesthetic considerations for the infant with shaken impact syndrome and
      pyloromyotomy: a case report.
AB  - This is a case report of an infant with shaken impact syndrome who required
      general anesthesia for the repair of pyloric stenosis. This infant suffered
      neurologic impairment from shaking, which was not only the major etiologic factor
      but the mechanism of injury as well. Shaking an infant can have devastating
      consequences. A thorough understanding of the mechanism of injury and the
      sequelae that result from this type of child abuse are paramount to prevent
      further damage if the infant requires general anesthesia. Anesthesia providers
      play a vital role in minimizing secondary injuries in infants with shaken impact
      syndrome.

PMID- 7502646
TI  - Differential diagnosis of malignant hyperthermia: a case report.
AB  - A 17-year-old male received general anesthesia for repair of a torn right knee
      anterior cruciate ligament. The medical history revealed manic-depressive
      psychosis, treated with lithium carbonate and sertraline hydrochloride, and
      asthma for which the patient occasionally used an albuterol inhaler. Induction
      with propofol, isoflurane, nitrous oxide, and oxygen was uneventful. Anesthesia
      was maintained by isoflurane, nitrous oxide, and oxygen. During the first 90
      minutes after induction, a persistent mild elevation in end-tidal carbon dioxide
      was noted, and several possible causes for this elevation were subsequently ruled
      out. A diagnosis of malignant hyperthermia was made when the patient exhibited
      tachycardia and a temperature increase, although some discussion remained
      regarding the possibility of neuroleptic malignant syndrome. The patient was
      treated successfully using a malignant hyperthermia protocol. Malignant
      hyperthermia may prove fatal if effective treatment is delayed. Favorable outcome
      and patient prognosis rely on astute vigilance, accurate diagnosis, and swift,
      appropriate treatment.

PMID- 7502647
TI  - [Quantitative psychopathology of depression: application of the Newcastle Scale].
AB  - Hypothalamo-pituitary axis disturbances, such as plasma cortisol escape after
      dexamethasone (DXM) administration or blunted TSH response to TRH, and sleep
      architecture abnormalities such as shortened REM latency are frequently
      encountered in depressive disorders. These anomalies only occur in a subgroup of
      depressed patients and could thus identify a biological or endogenous component
      to depressive illness. Several definitions of this endogenous depression have
      been proposed. In this regard, using biological criteria, the Newcastle scale
      remains the strongest validated clinical definition. In this study, 93 patients
      (58 women and 35 men) aged 15-79 years (mean: 42) who complained about a
      depressed mood were admitted for biological investigations (DXM and TRH tests,
      sleep EEG recording) after a drug wash-out period of at least 10 days. Patients
      were assessed with the Newcastle scale and diagnosed with RDC using the SADS.
      After the effects of age, gender and severity of illness were controlled for,
      multiple regression analyses showed that depressive pychomotor activity and
      weight loss were the 2 items of the Newcastle scale most contributing to explain
      the variances of the neuroendocrine tests results. Moreover, when the sample was
      dichotomized according to the presence of these 2 items, the 2 groups had
      significantly different post DXM cortisol values, TSH levels after TRH and REM
      latency values. The 2 groups (biological and non-biological) were then
      characterized using 16 depressive symptoms more frequently cited in 15
      operational definitions of endogenous depression. A logistic regression analysis
      showed that weight loss, anhedonia, early awakening, and morning worsening of
      mood were the 4 symptoms that best distinguished biological from non-biological
      patients group. These symptoms could reflect biological abnormalities in
      depression and form the core of the endogenous depression.

PMID- 7502648
TI  - [Quantification in psychiatry: from psychometrics to quantitative psychiatry].
AB  - The development of quantitative techniques to analyse psychopathological states
      is reviewed from the XVIIIth Century till today. As far as back as the XIXth
      Century, Quetelet, Louis and Galton introduced and advocated the use of
      quantitative methods in medical and psychological sciences. The advent of
      psychometry dates back 1905, when Alfred Binet published his Intelligence Scale.
      The construction of instruments like Wechsler and MMPI scales in the forties
      starts using psychometry in psychiatry. At end of World War II, historical
      factors (selection and guidance of military recruits) in conjunction with
      technical advancements (beginning of psychopharmacology, multivariate statistics
      development and first computers arrival) favor the growth of quantitative
      psychopathology that further takes four great different courses: 1. Psychometry
      proper, 2. Symptom-quantifying assessment scales such as BPRS or Hamilton scales,
      3. New nosological models constructed using quantified psychopathological data
      and mathematical procedures, 4. Diagnostic systems relying on operationalized
      criteria based on psychopathological quantification, such as DSM III.

PMID- 7502649
TI  - The Dissociation Questionnaire (Dis-G): development, reliability and validity of
      a new self-reporting Dissociation Questionnaire.

PMID- 7502650
TI  - Neuroendocrine and sleep variables in endogenous depression: the role of
      severity.

PMID- 7502651
TI  - [Memory disorders and psychopathological elements in patients with major
      depression].

PMID- 7502652
TI  - [Comparative analysis of clinical and biological findings in major depression in
      unipolar and bipolar patients].

PMID- 7502653
TI  - [Research strategies in the evaluation of depressive states].
AB  - The present paper discusses the respective benefits of a latent trait model and
      of factorial correspondence analysis in the research strategies of depression
      inventory construction. Results on the processing of the same list of depressive
      symptoms by both analyses are presented. The fact that, in questionnaires based
      on latent models, each answer brings an information closely dependent on its
      place in the hierarchical order is underlined. The latent trait strategy
      construction offers an accurate way to assess how patients recover from
      depression.

PMID- 7502654
TI  - Automatic analysis of pneumologic signals.

PMID- 7502655
TI  - Effects of body position on upper airway size and shape in patients with
      obstructive sleep apnea.

PMID- 7502656
TI  - Clinical correlates of sleep onset REM periods in major depression.

PMID- 7502657
TI  - [Cartographic analysis of sleep spindles in thalamic lesions].

PMID- 7502658
TI  - Sleep EEG in psychotic and non psychotic depressive patients matched for age,
      gender and polarity.

PMID- 7502659
TI  - Validation of the Newcastle Scale through sleep polysomnographic studies in major
      depression: comparison with age matched controls.

PMID- 7502660
TI  - The neuropsychological investigation of sleep: practical and methodological
      aspects.
AB  - Some stimulating areas in the field of neuropsychological research on sleep-wake
      behaviour are presented in this introductory paper using recent publications by
      eminent researchers. In the first part the cerebral asymmetry theory proposed by
      Ornstein is presented. Do the rhythmic oscillations of the sleeping brain go
      together with different forms of cognitive information processing? In the second
      part the work of some Italian researchers on dreaming experience in neurological
      patients is presented and commented. At a moment when the emphasis in sleep
      research is on medical-biological aspects, psychologists are challenged to
      produce some creative ideas in the field of neurocognition of sleep-wake
      behaviour.

PMID- 7502661
TI  - "Time since sleep" and "body clock" components of alertness and cognition.

PMID- 7502662
TI  - [Paradoxical sleep and memory processes in humans].
AB  - The beneficial effect of sleep on memory has often been reported. Moreover, REM
      sleep seems to be the best candidate for explaining this beneficial effect. Our
      aim in this paper is to point out the human literature concerning relationships
      between REM sleep and memory processes. The studies may be separated into three
      categories, on the basis of their methodological choice: effect of REM sleep
      deprivation on subsequent performance, effect of learning on subsequent REM sleep
      characteristics, enhancement of learning by acting on REM sleep. The data
      strengthen the assumption that REM sleep affects information processing. This
      topic "REM sleep and memory" is considered with respect to the chronopsychology
      of memory processes.

PMID- 7502665
TI  - Cognitive components of event-related potentials in obstructive sleep apnea
      syndrome: a study of 47 patients prior and after nCPAP treatment.

PMID- 7502664
TI  - P300, alertness and cognition.

PMID- 7502663
TI  - Assessing the residual effects of hypnotics.
AB  - The therapeutic efficacy of a hypnotic can not be judged solely on its ability to
      induce and improve sleep. Many of the older compounds produce residual effects
      the next morning, such as impaired performance, lack of concentration and day
      time sedation. This "hangover" phenomena will only serve to make the problem
      worse rather than better. The patient's quality of life would suffer, and this is
      particularly apparent in older patients. Zopiclone and zolpidem, two novel
      compounds, are superior to the older benzodiazepines in that they do not impair
      performance on tests of cognition, reaction time and memory the day following
      drug ingestion. These drugs may prove to be more beneficial and safer in people
      with sleep disorders who want to carry on with everyday life.

PMID- 7502666
TI  - Auditory information processing in sleep.

PMID- 7502667
TI  - [In memoriam Daniel Bobon].

PMID- 7502668
TI  - [A case of Folie a Deux in a husband-wife couple].
AB  - We described a case of "folie a deux" in a wife husband couple. We observed the
      syndrome gradually developing while following the husband in therapy for others
      reasons. Psychodynamic hypothesis for the occurrence and function of the disorder
      in this couple are discussed.

PMID- 7502669
TI  - [Genetics and manic-depressive psychosis: review and current findings].
AB  - The present article reviews the basic and recent findings of the genetics in
      manic-depressive illness. The different molecular genetic techniques that have
      been applied to this research field are presented. Results of linkage and
      association studies are discussed in regard to the main limitations of these
      approaches in psychiatric disorders. On the whole, linkage and association
      studies contributed to the localisation of some potentials vulnerability genes
      for manic-depression on chromosome X and 11 and more recently 18.

PMID- 7502670
TI  - [Traditional medicine and psychiatry: apropos of 3 experiences in Senegal, New
      Caledonia and Nepal].
AB  - The authors describe by turns their experience about indigenous medicine in
      Senegal, in New-Caledonia and in Nepal. They show that these indigenous medicines
      have common fundamental characteristics, although these various cultures are not
      linked together by their history. They compare these ways of thinking with
      occidental scientific medicine, and with the way of thinking of psychoanalysis.

PMID- 7502671
TI  - Multiple sclerosis: the impact on family and social life.
AB  - In a cross-sectional study of 117 randomly selected patients (52 men, 65 women)
      with definite multiple sclerosis, it was found that 76 percent were married or
      cohabitant, 8 percent divorced. Social contacts remained unchanged for 70
      percent, but outgoing social contacts were reduced for 45 percent. Ninety-five
      percent lived in own house or flat and 70 percent received disablement pension.
      More than half of the patients (56.4 percent) were dependent on help from close
      relatives, most frequently spouse. The need for help, the risk of divorce, loss
      of contact with relatives, difficulty in going out, need for structural changes
      in home and need for pension became greater with increasing physical handicap. No
      significant differences between gender were found. It is concluded that patients
      and relatives are under increased social strain, when multiple sclerosis
      progresses to a moderate handicap (Kurtzke Disability Rating Scale, 3-5).

PMID- 7502672
TI  - [The collective unconscious: from image to symbol].
AB  - With the help of clinical examples, the author tries to show how the therapeutic
      process works in Jung's theory of Unconscious: in the course of transference, the
      Unconscious generates Images which are coming from the Archetypes of Collective
      Unconscious. The interpretation of these Images and dreamer's associations trough
      transference, leads the patient to elaborate Symbols as carriers of a new sense
      for himself.

PMID- 7502673
TI  - [Effectiveness of psychotherapy in asthma: meta-analysis].
AB  - Various works have been done to find the efficiency of different psychotherapies
      of asthma. The results are sceptical and sometimes contradictory; this
      contradiction probably is due to the multiple methods or also to the various
      variables linked to the illness. The results of our meta-analyses on 74
      hypotheses chosen by specific criteria show the efficiencies of all these
      psychotherapies in asthma; however, these results are largely dependent on the 8
      variables taken into account.

PMID- 7502674
TI  - [In memoriam Charles Mertens de Wilmars].

PMID- 7502676
TI  - The image of the psychiatrist in motion pictures.
AB  - The psychiatrists who appear in commercial films can roughly be divided into 3
      stereotyped categories: 1. The funny and foolish character who lacks all common
      sense. He often is more deranged than his patients, but in a harmless way. 2. The
      intelligent, attractive, modest, warm, etc. psychiatrist who devotes his time and
      life to the well-being of his patients. He is too perfect to be true and is
      usually a rather boring character. 3. The thoroughly evil psychiatrist, who
      abuses his power for his personal ambition or enrichment. He endangers the health
      and life of his patients with his outrageous treatments and experiments. He is a
      classical horror movie character. Some of the implications that these prejudiced
      representations in popular culture have on the doctor-patient relationship will
      be discussed.

PMID- 7502675
TI  - [Countertransference and institutional stakes. The institution grappling with the
      ambivalence of state limit].
AB  - A paradoxal clinical case is described. First paradox: a patient borderline
      concerning personality, I.Q. and height involves all the medical and paramedical
      staff in her ambivalence. Second paradox: few members of the staff built with her
      a strong therapeutic link which allows to overcome the majority's negative
      countertransference. Third paradox: from a defensive behaviour, the patient
      succeeds to express her deep humanity through her drawings and poems. She is now
      taking the way of the autonomy.

PMID- 7502677
TI  - Possible neuroprotective therapy for Parkinson's disease.
AB  - Neuroprotective therapy for Parkinson's disease (PD) is a treatment intended to
      prevent or reduce neuronal degeneration. Since clinical studies to evaluate such
      an effect would be prolonged, the choice of agents for use as possible
      neuroprotective therapy is based on the results of in vitro and animal
      experiments. Free radicals are currently regarded as the most important factor in
      the progression of PD. One current possible neuroprotective therapy is reduction
      of levodopa dose, since levodopa is a source of free radical formation. Dopamine
      (DA) metabolism inhibition, and administration of the DA agonist bromocriptine
      that eliminates hydroxyl free radicals have neuroprotective effects
      experimentally. The other candidates for neuroprotective agents are still under
      development. However, those whose clinical use is permitted should be considered
      for use, since patients with long-standing PD cannot wait until the
      neuroprotective efficacy of these agents is confirmed by clinical study.

PMID- 7502678
TI  - Effect of vasopressin V1- and V2-receptor stimulation on blood pressure in DOCA
      salt hypertensive rats.
AB  - We recently reported that stimulation of the arginine vasopressin (AVP) V1
      receptor enhanced the pressor response in spontaneously hypertensive rats (SHR).
      In the present study, we investigated acute changes in systolic blood pressure
      (SBP) and heart rate (HR) after intravenous injections of AVP, OPC-21268 (a V1
      receptor antagonist), and OPC-31260 (a V2-receptor antagonist), in anesthetized
      DOCA-salt hypertensive rats (DOCA) and age-matched sham-operated Wistar rats
      (control) to determine whether the pressor effect is specific to SHR or is
      present in other hypertensive animal models. SBP increased significantly in DOCA
      rats 9 min after injection of AVP 5 ng/kg without a concomitant increase in HR.
      Neither OPC-21268 3mg/kg nor OPC-31260 3mg/kg caused significant changes in SBP
      or HR. SBP tended to increase when AVP was administered after injection of OPC
      31260. HR increased significantly 15 min after the combined treatment with OPC
      31260 and AVP in DOCA rats compared with control rats. SBP did not change
      significantly when AVP was administered after injection of OPC-21268 in DOCA or
      control rats, but HR decreased significantly from 1 to 4 min after injection of
      AVP in DOCA rats. Our results suggest that V1-receptor stimulation does not
      enhance the pressor response in the DOCA rat, which is a model of volume
      dependent hypertension, suggesting that the AVP system, especially V1-receptor,
      is not as important in the development or maintenance of hypertension in DOCA
      rats as in SHR.

PMID- 7502679
TI  - Histopathological evaluation of gastric mucosal environments in peptic ulcer
      using the endoscopic 5-point gastric biopsy method.
AB  - Although a strong association has been established between chronic Helicobacter
      pylori infection and peptic ulcers, the role of H. pylori is not necessarily
      causative because there are many patients infected with H. pylori who do not
      develop peptic ulcer. Therefore, we studied the relationship between the gastric
      mucosal environment and the development of peptic ulcers. We examined 165
      endoscopic biopsy specimens from the gastric mucosa of 33 patients with peptic
      ulcers using the 5-point gastric biopsy method. The follow-up biopsies done
      within 3 weeks were well correlated with the first biopsy samples. We also
      reviewed the clinicohistopathological findings of 2250 endoscopic biopsy
      specimens from 450 patients with active gastric and/or duodenal ulcers. Over 90%
      of the patients with duodenal ulcer, with or without gastric ulcer, had no fundic
      gland atrophy, and a high incidence of intestinal metaplasia and pyloric mucosal
      atrophy was found in the patients with gastric ulcer. These findings suggest that
      patients with concomitant active gastric and duodenal ulcers exhibit severe
      atrophic changes in the antral mucosa but not in the fundic mucosa.

PMID- 7502680
TI  - Effects of exposure to cigarette smoke on intestinal propulsion in rats.
AB  - The effects of acute exposure to cigarette smoke and systemic administration of
      nicotine on intestinal propulsion were investigated in rats. The propulsive
      activity was measured as migration of charcoal powder in the intestine. This
      activity was suppressed by acute exposure (10 min) to cigarette smoke and by
      nicotine (0.5 mg/kg x 2, s.c.) administration. This intestinal suppression was
      more marked in the rats given nicotine than in those exposed to cigarette smoke,
      whereas the plasma concentrations of nicotine in both rats were similar. These
      results suggest that acute exposure to cigarette smoke and nicotine
      administration delay gastric emptying and/or suppress intestinal propulsion, and
      that some components other than nicotine contained in cigarette smoke may
      attenuate the suppression of intestinal propulsion induced by nicotine.

PMID- 7502681
TI  - Lipid profiles of Helicobacter pylori and Helicobacter mustelae grown in serum
      supplemented and serum-free media.
AB  - Many of Helicobacter species have been found to have novel cholesteryl glucosides
      (CGs). To study the biosynthetic mechanism of CGs, the lipid profiles of H.
      pylori and H. mustelae grown in serum-supplemented and cholesterol-restricted
      serum-free media were investigated. In contrast to the serum-supplemented state,
      helicobacters had less CGs in the serum-free state; a trace amount of CGs and no
      CG was detected in H. pylori and H. mustelae, respectively. The proportion of
      total and individual phospholipid also showed significant alteration. Unknown
      lipids which did not contain phosphate and sugar were detected in the serum-free
      state, but not in the serum-supplemented state. The CGs were found to be
      distributed mainly in the membrane fractions, and one of the unknown lipids was
      found exclusively in the cytosol fraction. Based on these data, it is apparent
      that the CGs of helicobacters are synthesized by de novo uptake of cholesterol
      from the media. The unknown lipids detected in the serum-free state may be
      storage lipids, appearing in response to depletion of nutrients, especially
      cholesterol, or other factors in the media.

PMID- 7502682
TI  - Blood microvascular organization of the nasal-associated lymphoid tissue of the
      guinea pig: a scanning electron microscopic study of corrosion casts.
AB  - It has previously been confirmed that the guinea pig has aggregations of 10-20
      lymphoid follicles at the junction of the nasal cavity and the nasopharyngeal
      duct. The vascular architecture of this nasal-associated lymphoid tissue (NALT)
      was studied by the corrosion cast/scanning electron microscope method. The NALT
      was supplied by branches of the inferior nasal artery. These afferent arterial
      branches gave off arterioles to the follicles and the interfollicular regions,
      where the arterioles ramified into capillaries. Some of these arterioles reached
      the subepithelial region to form a single-layer dense capillary network. The
      subepithelial capillaries gathered into short collecting venules, which in turn
      drained into high endothelial venules (HEV) in the interfollicular region. The
      HEV, which also receives tributaries from the follicular and interfollicular
      capillary plexuses, descended in the interfollicular regions and finally flowed
      into the efferent veins at the bottom of the NALT. Indentations impressed by high
      endothelial cells (HEC) were prominent on the surface of the HEV casts, and their
      frequency was larger in the upper course or segments than in the lower. This
      suggests that the incidence of HEC in the upper segments is higher than in the
      lower segments, and these findings are consistent with the hypothesis that some
      substances which are taken up into the subepithelial capillaries and transported
      to the venules induce differentiation and maintain of HEVs.

PMID- 7502683
TI  - Rotationplasty for patients with osteosarcoma around the knee joint.
AB  - The results of rotationplasty for patients with osteosarcoma around the knee
      joint are presented. After an average observation period of 13.3 months, there
      has been no local recurrence or metastasis. The ankle joints (the new knee
      joints) of the patients were able to support their body weight with an average
      range of motion of 75 degrees. All patients could walk well without crutches and
      without risk of the giving way phenomenon. The average rate of the functional
      evaluation according to the re-modified system by Enneking was 84.5% (range, 80.0
      86.7%). No patient had psychological trouble in accepting the shortened and
      rotated extremity. The results show that rotationplasty is a useful
      reconstructive method for the treatment of osteosarcoma around the knee joint.

PMID- 7502684
TI  - Expression of Fas antigen and Bcl-2 protein in hepatocellular carcinoma.
AB  - Fas antigen (ag) is a cell surface protein known to trigger apoptosis in a
      variety of cells upon specific antibody binding. On the other hand, Bcl-2
      protein, an oncogene product located at the mitochondrial inner surface, prolongs
      cell survival by blocking apoptosis. In this study we examined the expression of
      Fas ag and bcl-2 protein in 17 cases of hepatocellular carcinoma (HCC) to
      determine their role on HCC. By flow cytometric analysis, mean (SD) value of the
      expression of Fas ag on hepatocytes derived from normal liver, diseased liver
      (chronic hepatitis or liver cirrhosis) and HCC was 5.8 (4.7)%, 10.3 (6.9)%, and
      24.0 (18.2)%, respectively. Fas ag expression on hepatoma cells was significantly
      greater than normal and diseased liver cells. The expression of Bcl-2 protein in
      normal liver, diseased liver and HCC was 4.3 (8.5)%, 0.8 (2.5)% and 2.1 (3.4)%,
      respectively, and the difference was not significant. These results suggest that
      induction of apoptosis may be a possible therapy against HCC.

PMID- 7502685
TI  - Evaluation of different ovarian stimulation protocols for in vitro fertilization.
AB  - In this study we evaluated retrospectively the efficacy of five different ovarian
      stimulation protocols in an in vitro fertilization program, in which 512 women
      were involved. Ovulation was induced by the following protocols: group I (271
      cycles): buserelin short protocol (1 mg/day, intranasally) with human menopausal
      gonadotropin/human chorionic gonadotropin (hMG/hCG); group II (45 cycles):
      buserelin (short protocol) with pure follicle stimulating hormone (p
      FSH)/hMG/hCG; group III (24 cycles): clomiphene citrate (100 mg/day) with
      hMG/hCG; group IV (122 cycles): hMG (3 ampules/day) and hCG; group V (113
      cycles): hMG/hCG and prednisolone (7.5 mg/day) after cycle programming with oral
      contraceptives. The lowest cancellation rate (3.3%) was noted in group I,
      followed by group V (9.7%). The highest number of follicles was observed in
      groups I (8.3 +/- 0.3; mean +/- SEM) and V (7.8 +/- 0.5). Also, more oocytes were
      retrieved in group I (7.2 +/- 0.3, p < 0.001), which were of good quality based
      on oocyte maturity as well as on the fertilization rate, and more embryos (4.5 +/
      0.3, p < 0.05) were developed. The correlation between estradiol and the total
      follicular volume on the day of hCG administration was also examined in the five
      groups. The best correlation (r = 0.6502) was found in group I, followed by group
      V (r = 0.5810). Significant differences were observed in the five groups with
      regard to the number of hMG ampules administered (p < 0.0001, F = 15.393) and the
      stimulation days (p < 0.0001, F = 35.32). Sixty-six clinical pregnancies were
      achieved: 37 (17.5%) in group I, seven (25.9%) in group II, one (10%) in group
      III, ten (15.6%) in group IV and 11 (15.5%) in group V (differences were not
      statistically significant). In conclusion, all five protocols were satisfactory
      in ovarian stimulation for in vitro fertilization, and gonadotropin releasing
      hormone (GnRH) analogs seemed to be more advantageous by reducing the
      cancellation rate, enhancing the number of oocytes retrieved and embryos
      developed and by improving the pregnancy rates.

PMID- 7502686
TI  - Bulimia nervosa and polycystic ovary syndrome.
AB  - Ninety-four female-female twins underwent a transabdominal ultrasound examination
      to detect polycystic ovaries. The scans of 52 individuals showed normal ovaries
      and 42 had evidence of polycystic ovaries. All the subjects were sent a bulimia
      investigation test (Edinburgh) (BITE) questionnaire for abnormal eating behavior.
      A total of 74 responses was received (79%). Overall, 76% of women with polycystic
      ovaries had an abnormal BITE score and their mean BITE score showed a significant
      increase compared to those with normal ovaries. Also, model fitting analysis
      suggested a strong genetic effect for bulimia using the BITE scoring system, and
      it provided strong evidence of a significant influence of environmental factors
      in the severity score of bulimia.

PMID- 7502687
TI  - Polycystic ovarian syndrome: pregnancy outcome following in vitro fertilization
      embryo transfer.
AB  - A retrospective study of a series of pregnant patients with polycystic ovarian
      syndrome following in vitro fertilization-embryo transfer was conducted to assess
      the outcome after ovarian stimulation by different protocols. Forty-one
      pregnancies were evaluated in patients with polycystic ovarian syndrome who
      conceived during in vitro fertilization-embryo transfer using human menopausal
      gonadotropin alone (17 pregnancies), or combined with gonadotropin releasing
      hormone analog (24 pregnancies). The demographic data of in vitro fertilization
      embryo transfer cycles and pregnancy outcome were compared with the use of
      Student's t-test, the Mann-Whitney U test and Fisher's exact test, where
      appropriate. Among the pregnancies that were initiated following treatment, the
      protocol of the combination of the two was not associated with a higher rate of
      deliveries. The rate of first-trimester abortions was not statistically different
      between the two groups. These results suggest that the combined use of
      gonadotropin releasing hormone agonist and human menopausal gonadotropin in an in
      vitro fertilization program may not have beneficial effects on pregnancy outcome
      in patients with polycystic ovarian syndrome.

PMID- 7502688
TI  - Natural killer activity in stage III and IV endometriosis: impaired cytotoxicity
      and retained lymphokine responsiveness of natural killer cells.
AB  - Our objective was to investigate the role of estrogens in the development and
      progression of endometriosis, and evaluate the in vitro boosting effect of
      lymphokines on the activity of natural killer cells from endometriosis patients,
      with respect to the estradiol concentrations. Natural killer activity of
      peripheral blood was evaluated in 42 endometriosis patients who underwent
      laparoscopy for pelvic pain, infertility and benign adnexal masses, and it was
      correlated with serum estradiol levels. Twenty-five women with moderate and
      severe disease were re-evaluated for immune and endocrine parameters 4-8 weeks
      after surgery, before any specific adjuvant medical treatment, and analyzed for
      in vitro responsiveness of cytotoxic cells to interferon (IFN) alpha 2 beta and
      interleukin-2 (IL-2) incubation. Patients with moderate and severe endometriosis
      showed a significant decrease of natural cytotoxicity when compared with patients
      with mild and minimal disease (p = 0.01). The decrease of immune reactivity was
      independent of a reduced representation of natural killer cells, and persisted
      after surgical removal of all macroscopic endometriosis foci. A significant
      inverse relationship was observed between natural killer activity and serum
      estradiol levels, which resulted in moderate and severe disease (r = -0.4, p =
      0.009) but not in stages I and II. The in vitro responsiveness of cytotoxic cells
      to lymphokine incubation was preserved; both IFN alpha 2 beta and IL-2 were able
      to increase the cytotoxicity of natural killer cells significantly from advanced
      stage patients (p = 0.014 and p = 0.006 for IFN alpha 2 beta and IL-2
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502689
TI  - Prospective evaluation of calcium and estrogen administration on bone mass and
      metabolism after ovariectomy.
AB  - We evaluated the effects of low-dose ethinylestradiol administration in the
      prevention of the rapid bone loss that follows ovariectomy in women. After 10-30
      days from surgery, patients received either a sole calcium supplementation 500
      mg/day (n = 20) or ethinylestradiol 20 micrograms/day in addition to the same
      daily calcium supplement (n = 21), for 12 months. In the control group, urinary
      hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein
      levels presented a substantial (p < 0.05) increase, while radial bone density
      significantly (p < 0.05) decreased 6 months after surgery. In the
      ethinylestradiol-treated group, the patterns of biochemical markers indicated
      that ethinylestradiol can restrain the bone remodelling processes. Radial bone
      density showed no significant modification during the 12 months' study period. In
      conclusions, these results demonstrate that the administration of 20
      micrograms/day of ethinylestradiol can prevent the rapid bone loss that follows
      ovariectomy.

PMID- 7502690
TI  - Transdermal estradiol and medroxyprogesterone acetate in hormone replacement
      therapy are both antioxidants.
AB  - We have evaluated the effects of the different components of hormone replacement
      therapy (HRT) on the production of free radicals in platelet membranes from
      menopausal women. The study included 12 women in menopause for at least 6 months
      to a maximum of 4 years. First, the effect was determined of progestin only
      during the administration of 20 mg/day medroxyprogesterone acetate for 5 days.
      The peroxide production level was measured on day 0 and day 5. The second set of
      experiments was carried out in the first month of cyclic HRT with transdermal
      estradiol 50 micrograms/day from day 1 to day 25 and medroxy-progesterone acetate
      from day 13 to day 25. In this experiment, the peroxide level was evaluated on
      days 0, 12 and 25. A significant reduction of peroxide level was observed after
      oral medroxyprogesterone acetate administration. During HRT, we observed a
      similar reduction in lipid oxidation at the peak of the estrogen effect, and a
      further decrease with the administration of medroxyprogesterone acetate. It is
      concluded that reduction of lipid peroxidation during HRT is not only due to
      estrogens, but also depends upon the combined action of sex steroids. This
      observation justifies not only the combined regimen (estrogens plus progestin) in
      HRT, but also the positive effects of progestins alone on patients who cannot use
      estrogens.

PMID- 7502691
TI  - Doppler analysis of uterine blood flow changes in spontaneous and medically
      induced menopause.
AB  - The aim of this study was to compare the uterine blood flow variations induced by
      chemical castration and spontaneous menopause. Thirty infertile patients were
      studied in the early follicular phase (day 5-7) and then treated with
      gonadotropin releasing hormone agonists (GnRH-a). On day 25 from GnRH-a
      injection, the suppressive effect was checked. The values obtained were compared
      with those found in 18 postmenopausal women (menopause < 5 years). All the
      subjects underwent transvaginal ultrasonography, Doppler analysis of uterine
      arteries, hormonal assay and evaluation of hematological and biochemical
      parameters. In all infertile patients, the GnRH-a suppressive effect was shown at
      the 25th day from the injection. Endometrium thickness decreased from 0.6 +/- 0.1
      mm to 0.3 +/- 0.1 mm (p < 0.05) and the pulsatility index increased from 2.52 +/-
      0.31 to 3.02 +/- 0.25 (p < 0.05). The plasma estradiol level fell from 48.2 +/-
      4.4 pg/ml to 13.6 +/- 7.9 pg/ml (p < 0.05). No other hormonal and biochemical
      parameters were significantly modified by GnRH-a. In postmenopausal women, the
      values of the studied parameters were similar to those found in the infertile
      GnRH-a-suppressed patients. These data show that GnRH-a induces vascular
      modifications similar to those induced by early post-menopause and that both are
      probably exclusively related to hypoestrogenism.

PMID- 7502692
TI  - Biological implications of estrogen and androgen effects on androgen receptor and
      its mRNA levels in human uterine endometrium.
AB  - It has been shown that some effects of testosterone are different from those of
      its 5 alpha-reduced metabolite, dihydrotestosterone. Briefly, activities of
      testosterone might be related to cellular differentiation, whereas
      dihydrotestosterone acts on cellular proliferation. The number of testosterone
      binding sites in the uterine endometrium was increased by estradiol dipropionate,
      and this increase was down-regulated by testosterone cypionate.
      Dihydrotestosterone-specific binding sites in the endometrium were not modulated
      by estradiol dipropionate and testosterone cypionate. The dissociation constants
      of the binding sites for testosterone and dihydrotestosterone were not altered by
      these steroids. Estradiol dipropionate with or without testosterone cypionate
      induced androgen receptor mRNA expression in the endometrium. In conclusion,
      testosterone might predominantly affect cellular differentiation in the
      endometrium.

PMID- 7502693
TI  - In vitro human growth hormone increases human chorionic gonadotropin and
      progesterone secretion by human placenta at term: evidence of a modulatory role
      by opioids.
AB  - We examined the in vitro effect of human growth hormone (hGH) on hormone
      placental production and the modulation by opioids of this function. Small
      placental fragments from 12 term placentas were incubated at 37 degrees C in a
      95% air and 5% CO2 atmosphere for 4 h with various concentrations of hGH (1-1000
      ng/ml) or naloxone (3-500 ng/ml). Both hGH and naloxone increased the
      concentrations of human chorionic gonadotropin (hCG) and progesterone in the
      media. The effect of the hGH was dose-dependent and statistically significant at
      10 ng/ml, while naloxone was able to increase hCG and progesterone production
      only at the highest doses (250-500 ng/ml). The concomitant treatment with
      ineffective doses of naloxone and hGH was able to enhance hCG and progesterone
      secretion reaching levels similar to those obtained with the highest doses of hGH
      alone. High naloxone concentrations significantly decreased both hCG and
      progesterone secretion induced by high doses of hGH. This study confirms the
      relevance of growth hormone in sustaining placental endocrine activities and
      indicates an effect of opioids in modulating these functions.

PMID- 7502695
TI  - Do the suppression criteria in GnRH-a cycles predict in vitro fertilization
      outcome?
AB  - The addition of gonadotropin releasing hormone analog (GnRH-a) to controlled
      ovarian hyperstimulation regimes has been reported to have several advantages,
      such as reduced cancellation rate, fewer premature luteinizations and increased
      clinical pregnancy rate. The aim of this study was to determine the effect of
      pituitary/ovarian suppression, in terms of the levels of luteinizing hormone
      (LH), estradiol and follicle stimulating hormone (FSH), and the duration of GnRH
      a administration, on in vitro fertilization (IVF) outcome. Retrospectively, 153
      IVF cycles with GnRH-a and human menopausal gonadotropin (hMG) were examined.
      After a minimum of 10 days of GnRH-a administration, the patients were started on
      hMG. The correlations were investigated between the fertilization rates, the
      numbers of retrieved oocytes and transferred embryos, the cancellation rates, the
      suppressed LH, FSH and estradiol levels, the total ampules of hMG used and the
      duration of GnRH-a usage. The duration of GnRH-a usage and the total ampules of
      hMG used were not correlated. The number of oocytes retrieved and total number of
      hMG ampules used showed weak correlations with suppressed levels of FSH (-0.297
      and 0.285, respectively). However, the fertilization, cleavage and pregnancy
      rates did not correlate with the LH, FSH and estradiol levels on hMG start days.
      In conclusion, for selected cases, 10 days of GnRH-a administration is sufficient
      to suppress endogenous gonadotropin levels. Since FSH and LH are protein hormones
      and their bioactivity may change in a manner that is unrelated to their
      immunological levels, it is not necessary to measure FSH, LH and estradiol levels
      to detect whether suppression is adequate.

PMID- 7502694
TI  - Vasoactive peptides and uterine vessels.
AB  - Endothelins and atrial natriuretic peptide (ANP) are vasoactive peptides with
      effects on the human uterine and umbilical arteries. Endothelin (ET) contracts
      the vascular smooth muscle. Both ETA- and non-ETA-non-ETB-receptors seem to be
      involved. Autoradiography reveals binding of ET to vascular smooth muscle. ANP
      counteracts the contractile effects of angiotensin II in the human uterine
      artery. Head-down tilt results in elevation of plasma ANP in healthy pregnant
      women, while the same manoeuvre induces down-regulation of the reninangiotensin
      aldosterone system in non-pregnant women and patients suffering from pre
      eclampsia.

PMID- 7502696
TI  - Use of GnRH analog for induction of the ovulatory surge of gonadotropins in
      patients at risk of the ovarian hyperstimulation syndrome.
AB  - A total of 32 patients undergoing in vitro fertilization (IVF) and 16 treated for
      ovulatory disturbances were stimulated with clomiphene citrate and human
      menopausal gonadotropin. Gonadotropin releasing hormone (GnRH) analog was used
      for induction of the ovulatory surge of gonadotropins, because of the risk of
      ovarian hyperstimulation syndrome. In four patients after IVF-embryo transfer and
      four patients after ovulation induction, single pregnancies were obtained. None
      suffered from ovarian hyperstimulation syndrome. The authors suggest that the use
      of GnRH analog for induction of the gonadotropin ovulatory surge prevents the
      development of ovarian hyperstimulation syndrome.

PMID- 7502697
TI  - Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass
      in healthy premenopausal women.
AB  - Bone mineral density (BMD) is under strong genetic control. Polymorphisms at the
      vitamin D receptor (VDR) gene have been recently suggested to account for up to
      75% of this genetic effect. We analyzed these polymorphisms, i.e., that of BsmI,
      TaqI, and ApaI restriction enzymes by PCR of the DNA in 189 healthy premenopausal
      women aged 31 to 57 years. For the BsmI polymorphism they were 17% BB
      homozygotes, 51% Bb heterozygotes, and 32% bb homozygotes, genotype frequencies
      that are very similar to those previously reported in other Caucasian populations
      of north European ancestry. Women in the three genotypes for any of the three
      polymorphisms were matched for age and did not differ in body weight, height,
      physical activity, nor smoking habits. We found no relationship between the
      genotype for any of the three polymorphisms nor bone formation and resorption
      rate assessed by five specific biochemical markers of bone turnover nor with BMD
      measured at the spine, proximal femur, forearm, and whole body by dual-energy X
      ray absorptiometry (DXA). We concluded that these polymorphisms are not
      predictive of bone turnover nor BMD in a sample of healthy premenopausal women
      drawn from the French population.

PMID- 7502698
TI  - Vitamin D receptor gene alleles and osteoporosis: an affirmative view.

PMID- 7502699
TI  - Vitamin D receptor gene alleles and osteoporosis: a contrasting view.

PMID- 7502700
TI  - Several anesthetics, but not diethyl ether, cause marked elevation of serum
      parathyroid hormone concentration in rats.
AB  - The effects of anesthetics on serum parathyroid hormone (PTH) concentrations were
      determined by a new homologous two-site immunoradiometric assay for rat PTH.
      Serum PTH concentrations (mean +/- SE) from ether-anesthetized rats (14.7 +/- 1.5
      pg/ml, n = 22) were not significantly different from those of decapitated
      unanesthetized female rats (13.0 +/- 1.8 pg/ml, n = 21). Serum PTH concentrations
      in pg/ml (n = 4-14) for other anesthetics tested were: ketamine, 12.5 +/- 1.1; Na
      pentobarbital, 23.3 +/- 2.4; methoxyflurane (inhalation), 42.2 +/- 6.8; and
      xylazine combined with ketamine, 51.4 +/- 11.3 pg/ml. The latter two
      concentrations were significantly (p < 0.001) higher than the values for all
      other anesthetics and decapitation. Elevation of serum PTH induced by
      pentobarbital or ketamine + xylazine increased with time under anesthesia.
      Neither serum Ca2+ concentrations nor pH differed among any of the groups. We
      conclude that anesthesia induced by pentobarbital, methoxyflurane, or ketamine +
      xylazine in rats leads to a marked elevation of serum PTH levels that appears to
      be related to the duration of anesthesia and not due to any measurable fall in
      serum Ca2+.

PMID- 7502701
TI  - Additive effects of weight-bearing exercise and estrogen on bone mineral density
      in older women.
AB  - The separate and combined effects of weight-bearing exercise and hormone
      replacement therapy (HRT) on bone mineral density (BMD) were studied in 32 women,
      60 to 72 years of age. HRT consisted of continuous conjugated estrogens 0.625
      mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days. Exercise
      consisted of 2 months of low-intensity exercise followed by 9 months of more
      vigorous weight-bearing exercise approximately 45 minutes/day, > or = 3
      days/week, at 65-85% of maximal heart rate. Lumbar spine and proximal femur BMD
      were significantly increased in response to exercise and to HRT, and total body
      BMD was significantly increased in response to HRT; neither exercise nor HRT had
      an effect on wrist BMD. The combination of exercise + HRT resulted in increased
      BMD at all sites except the wrist, with effects being additive for the lumbar
      spine and Ward's triangle and synergistic for the total body. Based on reductions
      in serum osteocalcin levels, it appears that increases in BMD in response to HRT
      and exercise + HRT were due to decreased bone turnover. The lack of change in
      serum osteocalcin and IGF-I in response to exercise alone suggests that increases
      in BMD were due to decreased bone resorption and not increased formation. Results
      indicate that weight-bearing exercise + HRT may be effective in preventing and/or
      treating osteoporosis. It is likely that the additive effects of weight-bearing
      exercise and HRT on bone mineral accretion, coupled with other adaptations to the
      exercise (i.e., increased strength and functional capacity), could effectively
      reduce the incidence of falls and osteoporotic fractures.

PMID- 7502702
TI  - Changes in bone mineral density and markers of bone remodeling during lactation
      and postweaning in women consuming high amounts of calcium.
AB  - A randomized clinical intervention trial to determine effects of lactation and 1
      g of calcium (Ca) on bone remodeling was conducted in 15 women (calcium = 7,
      placebo [P] = 8) consuming 1.3-2.4 g of Ca/day from diet + prenatal supplement.
      Study periods were baseline, < or = 2 weeks postpartum; lactation, 3 months
      lactation; and postweaning, 3 months postweaning. Bone mineral density (BMD)
      corrected for body weight was determined by dual-energy X-ray absorptiometry
      (DXA). Indicators of calcium metabolism, bone turnover, and lactation were
      measured: calcium metabolism, parathyroid hormone (PTH), 25-hydroxyvitamin D
      (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D); bone turnover, formation,
      procollagen I carboxypeptides (PICP), osteocalcin, and bone alkaline phosphatase
      (B-ALP), resorption, tartrate resistant acid phosphatase (TRAP); and lactation,
      prolactin (PRL). Mean BMD changes differed by site: baseline to lactation -4.3%
      (P) (p < 0.04) and -6.3% (Ca) (p < 0.01) at the lumbar spine (L2-L4) and 5.7%
      gains of the ultradistal (UD) radius (Ca) (p < 0.04); lactation to postweaning, 
      6% to -11% at all sites of the radius and ulna (Ca, P) (p < 0.04) +3% at L2-L4
      (Ca) (p < 0.03); baseline to postweaning, (UD) radius -5.2% (P) (p < 0.03), UD
      radius + ulna -6% to -8% (Ca, P) (p < 0.04) but no significant loss of L2-L4 or
      total body. Bone turnover markers were higher at lactation than postweaning: PICP
      (+34%, p < 0.001), osteocalcin (+25%, p < 0.01), TRAP (+11%, p < 0.005) as well
      as PRL (+81%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502703
TI  - Triiodothyronine potentiates the stimulatory effects of interleukin-1 beta on
      bone resorption and medium interleukin-6 content in fetal rat limb bone cultures.
AB  - It has been demonstrated that thyroid hormones stimulate osteoclasts indirectly
      and that this effect is mediated by products of other cell types present in bone.
      To determine if interleukin-6 (IL-6) could be a mediator of thyroid hormone
      action, we investigated the effect of 3,5,3'-triiodothyronine (T3) on bone
      resorption (45Ca release) and on the IL-6 concentration in medium from cultured
      19-day-old fetal rat limb bones. T3 alone increased 45Ca release significantly
      only at a fairly high concentration (10(-6)M) under the conditions used. T3
      alone, over a 10(-11)-10(-6) M concentration range, failed to elicit a detectable
      effect on the medium IL-6 content. However, T3 potentiated the stimulatory effect
      of interleukin-1 beta (IL-1 beta) on IL-6 production in a dose-dependent manner.
      T3, 10(-8) M, also significantly increased IL-1 beta-stimulated calcium release.
      Inhibition of IL-1 beta with 1 muM interleukin-1 receptor antagonist (IL-1ra)
      abrogated the potentiating effects of T3 on IL-1 beta-stimulated IL-6 production
      and blocked the combined effect of T3 and IL-1 beta on 45Ca release. One
      micromolar indomethacin significantly, but not completely, inhibited the effect
      of IL-1 beta, as well as the combined effect of IL-1 beta and T3 on resorption
      and IL-6 production, indicating the involvement of prostaglandins in these
      actions. Consistent with this, 1 microM prostaglandin E1 (PGE1) significantly
      increased both the IL-6 production and the calcium release. By potentiating the
      effect of IL-1 beta, T3 increased bone resorption at much lower
      concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502704
TI  - Phosphate transport in immortalized cell cultures from the renal proximal tubule
      of normal and Hyp mice: evidence that the HYP gene locus product is an extrarenal
      factor.
AB  - Whether renal phosphate wasting in X-linked hypophosphatemia (XLH) results from
      an intrinsic renal or humoral defect remains controversial. In studies of the
      murine homolog of XLH, harboring the Simian Virus 40 (SV40) large T antigen, we
      obviated the influence of renal cell heterogeneity and impressed memory by
      comparing Na(+)-phosphate cotransport in immortalized cells from the S1 segment
      of the proximal tubule. Cells from SV40 transgenic normal and Hyp mice exhibit
      characteristics of differentiated proximal tubule cells including gluconeogenesis
      and alkaline phosphatase activity. Surprisingly, however, we found two distinct
      populations of cells from the S1 proximal tubule of both normal and Hyp mice. In
      one, PTH treatment increases cAMP accumulation, while in the other both PTH and
      thyrocalcitonin enhance cAMP production. Kinetic parameters for Na(+)-phosphate
      cotransport were similar in both subpopulations of cells from normal (Km, 0.29 +/
      0.03 vs. 0.39 +/- 0.04 mM; Vmax, 4.6 +/- 0.6 vs. 5.2 +/- 0.4 nmol/mg/5 minutes)
      and Hyp mice (0.33 +/- 0.02 vs. 0.26 +/- 0.04; 6.0 +/- 0.7, 4.8 +/- 0.6). More
      importantly, phosphate transport in S1 cells of either subpopulation from Hyp
      mice is no different than that of normals. These data indicate that renal
      proximal tubule cells from Hyp mice have intrinsically normal phosphate transport
      and support the hypothesis that a humoral abnormality underlies renal phosphate
      wasting in XLH.

PMID- 7502705
TI  - Effect of ovariectomy on cancellous bone in the hypophysectomized rat.
AB  - This experiment studied the effects of hypophysectomy (HX) and ovariectomy (OV)
      on cancellous bone in the proximal tibia and distal 5th lumbar vertebra by
      dynamic histomorphometry. Forty-eight female Sprague-Dawley rats, 3 months of
      age, were divided into age-matched control, HX, OV, and HX + OV (HO) groups. Ten
      rats were sacrificed at 3 months of age as baseline controls, and the rest of the
      animals were sacrificed 5 weeks after the surgery. While the age-matched
      controls, and the OV rats significantly increased in body weight compared with
      the baseline control rats, cancellous bone volumes in the proximal tibia and
      distal 5th lumbar vertebra increased in the age-matched controls and decreased in
      the OV rats. In the HX and HO rats, body weight equaled baseline control values,
      and their cancellous bone volumes were decreased with a poorer trabecular
      architecture in both bone sites. In all HX, OV, and HO rats, uterine weight and
      serum estradiol were significantly decreased. OV significantly increased
      longitudinal bone growth and the tissue- and surface-based bone formation and
      bone resorption parameters in both the proximal tibia and 5th lumbar vertebra (p
      < 0.05). HX alone or HO significantly decreased longitudinal bone growth and the
      tissue-based bone formation rate without significantly affecting surface-based
      bone formation and bone resorption parameters when compared with the age-matched
      controls. No significant differences were detected in any variables between the
      HX alone and HO rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502706
TI  - EndothelinB receptor activation enhances parathyroid hormone-induced calcium
      signals in UMR-106 cells.
AB  - In studies of the regulation of parathyroid hormone (PTH) signal transduction, we
      observed that the peptide endothelin-1 (ET) added prior to PTH greatly increased
      the calcium transients elicited by PTH in UMR-106 osteosarcoma cells and mouse
      primary osteoblastic cells. Enhancement by ET also occurred in the presence of
      EGTA. The ETB receptor-specific agonist sarafotoxin 6c (S6c) likewise enhanced
      PTH-induced Ca2+ transients. Blocking the ETA receptor-mediated component of the
      ET signal with BQ123 failed to abolish enhancement of PTH responses by ET. The
      nonselective ETA/ETB receptor antagonist PD 142893 blocked both ET and S6c
      induced enhancement of the PTH responses. Prostaglandin F1 alpha (PGF1 alpha)
      pretreatment also maximally potentiated PTH responses, whereas alpha-thrombin,
      epidermal growth factor (EGF), or prostaglandin E1 (PGE1) did not affect the PTH
      responses. Neither active phorbol ester nor forskolin mimicked the ET effect. The
      ET effect was not prevented by indomethacin, NG-mono-methylarginine, genistein,
      pertussis toxin, 4-aminopyridine, tetraethylammonium chloride, okadaic acid, or
      long-term treatment with phorbol-12,13-dibutyrate. ET pretreatment did not
      abolish the inhibition of PTH signals by PTH(3-34), although in ET-pretreated
      cells the suppression of the PTH signal by PTH(3-34) was not as great. ET
      pretreatment did not enhance the cAMP response to PTH; rather, there was a
      significant inhibition of the cAMP response. Thus, the calcium signal elicited by
      PTH is selectively modulated by activation of the ETB receptor.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7502707
TI  - Treatment with growth hormone and IGF-I in growing rats increases bone mineral
      content but not bone mineral density.
AB  - Human growth hormone (hGH) and insulin-like growth factor I (IGF-I) both
      stimulate bone formation and have been proposed as therapeutic agents for
      osteoporosis. We examined the effect of hGH and IGF-I alone and in combination on
      bone size, bone mineral content (BMC), and bone mineral density (BMD) in 10- to
      12-week old growing female Sprague-Dawley rats. Sixty rats were assigned to
      treatment with either placebo, hGH, IGF-I, or both for 4 weeks. After 4 weeks,
      the right femurs and tibias were excised, and ex vivo BMC and the area of the
      tibia and femur were measured by dual-energy X-ray absorptiometry (DXA); volume
      of these bones was measured by Archimedes' principle. In addition, proximal
      tibial bone density was measured directly by peripheral quantitative computerized
      tomography (pQCT). Bone length, area, and volume in all treated groups was
      greater than controls. Areal bone density by DXA (BMC/area) was higher in IGF
      treated rats and lower in GH-treated rats than in controls. Volumetric bone
      density (BMC/volume) was lower in treated groups than in controls. Measurements
      by pQCT confirmed that true bone density was lower in all treated groups than in
      controls. We conclude that treatment with hGH or IGF-I increased bone size and
      mineral content but decreased bone density in growing rats. Because areal
      correction of BMC did not adequately correct for the increased bone volume in IGF
      treated rats, results of areal bone density by DXA should be interpreted with
      caution when treatment causes a disparity in bone size between groups.

PMID- 7502708
TI  - Chondrocytes isolated from mature articular cartilage retain the capacity to form
      functional gap junctions.
AB  - The distribution, expression, and functionality of gap junctions was examined in
      bovine chondrocytes (BCs) isolated from mature articular cartilage. BC cells
      displayed immunoreactivity for connexin 43 (Cx43), a specific gap junction
      protein. Cx43 protein expression was confirmed by Western blot analysis, and Cx43
      mRNA was detected by nuclease protection assay. Additionally, BCs were shown to
      be functionally coupled, as revealed by dye transfer studies, and octanol, a gap
      junction uncoupler, greatly attenuated coupling. Furthermore, confocal microscopy
      of fluo-3 loaded BC cells revealed that deformation-induced cytosolic Ca2+ ion
      (Ca2+) signals propagated from cell-to-cell via gap junctions. To our knowledge,
      this is the first evidence suggesting that chondrocytes isolated from adult
      articular cartilage express functional gap junctions.

PMID- 7502709
TI  - Endogenous bone-resorbing factors in estrogen deficiency: cooperative effects of
      IL-1 and IL-6.
AB  - Estrogen deficiency causes a marked bone loss by stimulating osteoclastic bone
      resorption. To explore the endogenous bone-resorbing factors involved in estrogen
      deficiency, we examined the bone-resorbing activity present in the supernatant
      fraction of mouse bone marrow collected from ovariectomized (OVX) mice. Adding
      bone marrow supernatants at 20-80% to organ cultures of mouse long bones dose
      dependently stimulated bone resorption. The endogenous bone-resorbing activity
      present in bone marrow supernatants from OVX mice was much higher than that from
      sham-operated mice 2-4 weeks after surgery, and it was significantly diminished
      by indomethacin in vitro. Anti-IL-1 alpha antibody completely neutralized the
      bone-resorbing activity present in bone marrow supernatants from OVX mice.
      Antibodies against IL-1 beta, IL-6, and IL-6 receptors also neutralized it, but
      partially. The concentration of IL-1 alpha measured by ELISA was much higher in
      bone marrow supernatants than in sera, but it was not appreciably changed before
      or after OVX. The concentration of IL-1 beta in bone marrow supernatants from OVX
      mice was less than the detection limit. OVX stimulated IL-1 activity in bone
      marrow supernatants measured by means of the proliferation of thymocytes.
      However, the level of IL-1 alpha present in bone marrow supernatants from OVX
      mice was insufficient to stimulate bone resorption. Compared with the serum
      concentration, bone marrow supernatants contained a much higher level of IL-6 as
      well, and it was further increased by OVX. However, IL-6 alone present in bone
      marrow supernatants from OVX mice again did not stimulate bone
      resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502711
TI  - Multiple molecular forms of pyridinolines cross-links excreted in human urine
      evaluated by chromatographic and immunoassay methods.
AB  - The measurement of the collagen cross-links, hydroxylysylpyridinoline (HP) and
      lysylpyridinoline (LP), excreted in urine either in free or peptide-bound forms
      represents the most extensively investigated biochemical marker of bone collagen
      degradation. We studied the urinary molecular forms of pyridinolines after
      separation in free and peptide-linked fractions by chromatography and serial
      dialysis. The pyridinoline amounts of molecular species (free, < 1000 D, 1000
      3500 D, 3500-10,000 D, and > 10,000 D) were evaluated by high performance liquid
      chromatography (HPLC) as well as with the two newly introduced enzyme-linked
      immunosorbent assay (ELISA) methods for determination of free pyridinolines
      (collagen Pyrilinks and collagen Pyrilinks-D). The variability of urinary
      pyridinoline forms were studied in healthy adult control subjects (n = 10, 38.4
      +/- 7.5) years), in adolescents (n = 10, 16 +/- 3.3 years), and in elderly
      subjects with vitamin D insufficiency (n = 10, 87.3 +/- 4.3 years). Free and
      peptide-conjugated pyridinolines with MW < 1000 D constitute the major part of
      urinary cross-links in all groups, with a significantly lesser excretion in
      elderly patients than in adolescent groups. Expressed as a percent of total cross
      links, urinary free pyridinolines assessed by direct HPLC are less in elderly
      subjects (HP = 34.2 +/- 6.2%, LP = 32.7 +/- 7.6%) than in adolescents (HP = 45.8
      +/- 10.8%, p = 0.0065 and LP = 47.8 +/- 12.1%, p = 0.012) and in healthy adults
      (HP = 39.3 +/- 11.5%, NS and LP = 38.1 +/- 9.3%, NS).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7502710
TI  - Regulation of plasminogen activation, matrix metalloproteinases and urokinase
      type plasminogen activator-mediated extracellular matrix degradation in human
      osteosarcoma cell line MG63 by interleukin-1 alpha.
AB  - Plasmin-mediated extracellular proteolysis has been implicated in the degradation
      of bone in normal and pathological conditions. Normal and malignant osteoblasts
      can produce both tissue-type plasminogen activator (t-PA) and urokinase-type
      plasminogen activator (u-PA). We have used the osteosarcoma cell line MG63 to
      address the question of whether the enhanced bone turnover in osteosarcomas is
      mediated by t-PA or by u-PAA and to study the effect of the cytokine interleukin
      1 alpha (IL-1 alpha), known to influence bone degradation, on the plasminogen
      activator production and extracellular matrix degradation in malignant
      osteoblastic cells. Furthermore, the effect of IL-1 alpha on the synthesis of
      matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was analyzed. u-PA
      production by MG63 was high (approximately 180 ng/10(6) cells/24 h). Also t-PA
      and PAI-1 production was observed. u-PA production was rapidly increased in MG63
      by IL-1 alpha (10 ng/ml), whereas an effect on t-PA production was only found
      after a prolonged incubation and hardly any effect of IL-1 alpha on PAI-1
      production was observed. mRNA analysis revealed similar effects. u-PA receptor (u
      PAR) mRNA was detectable in MG63 cells and could be increased by IL-1 alpha after
      24 h. In MG63, u-PA-mediated extracellular matrix degradation was detectable, and
      IL-1 alpha increased the u-PA-mediated matrix degradation (approximately 2-fold).
      Under control conditions in MG63, only MMP-2, TIMP-1, and TIMP-2 mRNA could be
      observed. After the addition of IL-1 alpha, a very rapid increase in MMP-1 and
      MMP-3 mRNA could be observed as well as a moderate increase in TIMP-1 mRNA. The
      presence of MMP-2 was demonstrated by gelatin zymography. These results show that
      IL-1 alpha can stimulate u-PA production and can regulate extracellular
      proteolytic activity mainly via u-PA induction in the MG63 osteosarcoma cell
      line. Furthermore, IL-1 alpha has a strong stimulating effect on the production
      of MMP-1 and MMP-3. These findings suggest that u-PA and possibly MMP-1 and MMP-3
      play an important role in the process of bone turnover in osteosarcomas.

PMID- 7502712
TI  - Bone structure in postmenopausal hyperparathyroid, osteoporotic, and normal
      women.
AB  - The purpose of this study was to test the hypothesis that patients with mild
      primary hyperparathyroidism are protected against postmenopausal (PM) loss of
      cancellous bone architecture. To achieve this, we compared bone structure and
      turnover in iliac bone biopsies from three groups: 16 women with mild primary
      hyperparathyroidism (PHPT; 58.2 +/- 2.2 years, 11.5 +/- 1.7 years PM), 17 women
      with untreated primary osteoporosis (OP; 65.1 +/- 2.0 years, 17.2 +/- 2.3 years
      PM), and 31 healthy women (N; 59.8 +/- 1.4 years, 13.4 +/- 1.5 years PM). The
      bone formation rate was significantly higher in PHPT than in either OP or N, and
      not different between OP and N. Cancellous bone volume, total strut length, and
      indices of connectivity (node number, node to node strut length, and node to
      terminus ratio) were significantly lower in OP than in either PHPT or N but were
      the same or higher in PHPT than in N. Indices of disconnectivity were
      significantly lower in PHPT than in N, whereas they were the same or higher in OP
      than N. The data were also analyzed in subgroups matched by years PM with no
      changes in the results. These findings indicate that osteoporotic patients with
      normal bone turnover have low bone volume and microarchitectural deterioration,
      while patients with mild PHPT have normal bone volume and normal or greater
      trabecular connectivity despite higher bone turnover. These findings suggest that
      mild PHPT protects against the loss of cancellous bone structure that normally
      follows menopause.

PMID- 7502713
TI  - Age and temperature related changes to the ultrastructure and composition of
      human bone mineral.
AB  - This X-ray diffraction (XRD) investigation of heat-treated human femoral bone
      showed that the main mineral phase of both unheated bone and bone heated to 600
      degrees C resembled that of a poorly crystalline form of hydroxyapatite. The rod
      shaped apatite crystals in unheated bone persisted in bone heated up to 400
      degrees C. Recrystallization at approximately 600 degrees C, produced larger
      crystals, which either retained their original morphology or changed to tabular
      or equidimensional shapes. The size of the apatite crystals in unheated and
      heated bone specimens was dependent on both temperature and age. When heated
      above 600 degrees C the crystallinity of the bone mineral increased, and the XRD
      pattern more closely resembled that of hydroxyapatite. Partial decomposition of
      the hydroxyapatite phase to calcium oxide above 1000 degrees C, and beta
      tricalcium phosphate, alpha-tricalcium phosphate, and calcium oxide phosphate
      between 1200 degrees C and 1400 degrees C, indicated that the original apatite
      phase was both calcium deficient and contained carbonate. The relative peak
      intensities of the thermal decomposition products were related to some extent to
      the age of the deceased person and reflected the compositional changes that occur
      during bone aging. Because the thermally induced changes to the composition and
      ultrastructure of bone mineral were influenced by the age of the individual, this
      investigation proposed that the heat treatment of bone tissue may offer an
      alternative way of studying bone aging.

PMID- 7502714
TI  - Microcallus formations of the cancellous bone: a quantitative analysis of the
      human spine.
AB  - Microcallus formations are demonstrable in nearly all spongy bone by means of
      suitable preparation techniques. Histologically, these structures are immature
      fibrous bone. Their genesis, frequency, and importance are largely unknown. To
      address these issues, 26 normal human spines, 11 osteoporotic spines, and
      different parts of the skeleton (femur head, iliac crest) were investigated for
      microcallus using a new preparation technique--allowing a combined 2- and 3
      dimensional analysis. According to our analysis, microcallus formation occurs
      frequently in persons older than 45 years of age. These formations are mainly
      localized in the lower thoracic and lumbar spine and are obviously more frequent
      in females than in males. In individuals with a trabecular bone volume (BV/TV) in
      the spine below 11%, microcallus formations occur regularly. But the number of
      microcallus formations depends more on the microarchitecture of the cancellous
      bone (trabecular bone pattern factor, TBPf), than on individual trabecular
      parameters (trabecular number, TbN; trabecular bone volume, BV/TV; and trabecular
      thickness, TbTh). In about 33% of cases microfractures are demonstrable in the
      center of the microcallus formation. It is unclear whether microcallus may be the
      result of a nontraumatic process. In therapy studies the bone mass could be
      misrepresented due to the amount of microcallus. Although it indicates
      instability of the bone structure, microcallus formation is not only a negative
      mechanism, but stabilizes and regenerates the bone tissue. Furthermore, complete
      new trabeculae can be formed due to bridges of microcallus between the remnant
      trabeculae. Osteoporosis is not the result of an inability to form microcallus
      formations.

PMID- 7502716
TI  - Proceedings of the International Symposium on Stereotactic Neuro-Radio-Surgery.
      Vienna, October 11-14, 1992.

PMID- 7502715
TI  - The potential role of fibroblasts in periprosthetic osteolysis: fibroblast
      response to titanium particles.
AB  - Periprosthetic osteolysis with or without aseptic loosening is a major clinical
      problem in total hip arthroplasty. While the macrophage response to prosthetic
      wear debris and its role in periprosthetic osteolysis has been extensively
      studied, information regarding other cell types (fibroblasts, osteoblasts) is
      limited. This study explored the response of fibroblasts to particulate wear
      debris. Fibroblasts isolated from interfacial membranes of patients with failed
      total hip replacements and normal synovial tissue, when challenged with small
      sized ( < 3 microns) titanium (Ti) particles, responded with significantly
      enhanced expressions of collagenase, stromelysin and, to a much lesser extent,
      their tissue inhibitor of metalloproteinases (TIMP). These "regulated"
      expressions at both mRNA and protein levels were correlated with the size and
      composition of particles. De novo protein synthesis was required for the
      regulation of these mRNAs. A similar effect could be induced by the treatment of
      the cells with particle-free conditioned medium from Ti particle-stimulated
      fibroblasts. Furthermore, this conditioned medium significantly suppressed the
      mRNA levels of procollagen alpha 1 (I) and alpha 1 (III) in osteoblast-like MG-63
      cells. It is concluded that fibroblasts stimulated with certain particle debris
      may play an important role in periprosthetic osteolysis by releasing bone
      resorbing metalloproteinases and mediator(s) which resulted in suppressed
      collagen synthesis in osteoblasts.

PMID- 7502717
TI  - Neuroanatomical details under endoscopical view--relevant for radiosurgery?
AB  - Both, neuroendoscopy and radiosurgery, are upcoming techniques in neurosurgery
      and become nowadays more and more important. In planning radiosurgical
      interventions it is very important to have both, the information about the
      morphology of the pathology itself, and also a clear understanding from the
      surrounding structures. Neuroendoscopic techniques gives the possibility to
      demonstrate well known structures without prior dissection. This paper focuses on
      these anatomical informations which might be relevant in planning further
      radiosurgical interventions especially in cases of the vascularization of the
      cranial nerves and the arachnoid membranes, these structures appears much more
      complex than described in "common" neuroanatomical textbooks. Endoscopic
      techniques also better demonstrate the real in vivo relationships and gives so a
      better understanding for interpreting "planning" MRI and CT scans. We therefore
      consider that neuroanatomical studies under a neuroendoscopical view are very
      important and could be very helpful in planning radiosurgical intervensitons.

PMID- 7502718
TI  - Malignant transformation of benign gliomas during interstitial irradiation.
AB  - Interstitial curietherapy with 125-Iodine is an effective therapeutic option in
      the treatment of low grade gliomas. Four cases with astrocytoma grade II are
      presented, where tumour growth characteristics have changed to anaplasia during
      interstitial irradiation after a primary period of tumour regression. Anaplastic
      transformation could be due to a radiation effect or an insufficient therapeutic
      influence of interstitial irradiation on natural tumour progression of glioma
      growth due to genetic events.

PMID- 7502719
TI  - Stereotactic radiosurgery: the Lyon experience.
AB  - From 10/1989 to 12/1992, 135 patients were treated, in Lyon, by Stereotactic
      Radiosurgery (RS) +/- External beam Radiotherapy (EBRT). Indications were AVMs or
      tumours that could not be cured by embolisation or/and surgery and are not larger
      than 30 to 35 mm. Lesions received 15 to 20 Gy (70% isodose) in one course. Among
      the 42 AVMs, only one rebled 6 months after RS and 9/15 had clinical improvement.
      Thirty-one had a radiological follow-up of 4 to 29 months after RS. Ten were
      totally obliterated, seven regressed more than 80% and six had a reduction of 50
      to 80% of their AVM. Three grade 3 radio necrosis occurred for a cerebral trunk
      AVM and two large lesions. Three of the 15 treated meningiomas progressed after
      RS, 2 of them were controlled by conventional surgery. Four out of nine
      presenting symptoms had clinical improvement and, with a radiological follow-up
      of 4 to 24 months, 5 were stabilised and 6 regressed. Two grade three
      complications occurred for large lesions. The biological and radiological results
      of RS were good for the 42 treated pituitary adenomas but the high visual
      complication rate (12/42 with 8 grade 3) was too important and we stopped RS for
      these tumours except for small (less than 2 cm) adenoma at some distance from the
      optic chiasma. The visual complications were related to the tumour volume, the
      distance between the adenoma and the visual tract and pre-existent visual
      alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502720
TI  - Suction fixation system for stereotactic radiosurgery of intraocular
      malignancies.
AB  - We designed a suction fixation system for the radiosurgical treatment of
      intraocular malignancies with the Leksell gamma unit (gamma knife). OUr device
      consists of a circular suction chamber and an adjustable unit to be fixed to the
      Leksell stereotactic head frame. All components are made of plastic materials in
      order to avoid artifacts in CT or MRT imaging. A permanent suction of 600 to 800
      millibars is provided by a standard vacuum pump, powered by a portable battery.
      Suction times up to 40 minutes were well tolerated in all cases. In the gamma
      knife of the Neurosurgical Department at the University of Vienna, we
      successfully used this device. Up to January 1994 we have performed 19
      radiosurgical treatments in 9 patients with large or extra-large uveal melanomas
      and in one patient suffering from a choroidal metastasis.

PMID- 7502721
TI  - CT-guided needle biopsy of intracranial tumours: results in 118 consecutive
      patients.
AB  - The purpose of this paper is to evaluate the efficacy and safety of CT-guided
      needle biopsies and to determine the optimal indications for this technique. The
      case histories of 118 patients who underwent a CT-guided biopsy for brain lesions
      during a six-year period, from November 1986 to September 1992, were reviewed.
      During a preliminary CT-scan, the entry site was determined and localized using a
      radio opaque marker and the safest route to the lesion was chosen. One hundred
      and thirty four procedures were performed in 118 patients. A positive diagnosis
      of tumour was obtained in 106 patients (89.8%). Repeat procedures were required
      in 18 patients. High-grade gliomas were the more common lesions (55.1%).
      Morbidity and mortality was assessed over the 30-day period after the procedure.
      Nine patients died during this time. Eight patients from day 3 to day 30 in the
      expected course of their disease and one within 48 first hours from neurological
      deterioration following the procedure. We found that CT-scan guided biopsies are
      a safe and accurate way to obtain brain tissue specimens for pathological
      diagnosis in selected cases. For superficial and large tumours it is a simple,
      fast and effective procedure.

PMID- 7502722
TI  - The role of stereotactic biopsy in radiosurgery.
AB  - Radiosurgery offers a very powerful, minimally invasive therapeutic tool in the
      modern treatment of intracranial lesions. A direct contact with the lesion, as
      always takes place, e.g. in a stereotactic biopsy or microsurgical operation, is
      no longer an absolute prerequisite. Treatment planning is done using modern
      imaging techniques like computer assisted tomography (CT) or magnetic resonance
      imaging (MRI). Both provide high resolution and contrast images. The lesions can
      be displayed with high accuracy. The specificity of these techniques is adequate
      enough to provide neuropathological data which are a prerequisite for treatment?
      In 1991 we published a retrospective study in which the diagnosis based on CT was
      compared with the histological diagnosis following stereotactic biopsy on a
      series of 181 patients with intracranial processes. We could show clearly that CT
      alone does not offer a reliable basis for therapy planning. Overall CT-scan was
      inaccurate in 22% of the cases. Now in an additional series of 195 patients with
      intracranial processes, we have compared the MRI diagnosis with the
      neuropathological diagnosis. MRI results and the neuropathological diagnosis
      based on microsurgical operation were compared and evaluated according to the
      following criteria: 1. Absolute agreement between MRI and histological diagnosis.
      2. No agreement between MRI and histological diagnosis. 3. Conditional agreement:
      the MRI result offered several differential diagnoses one of which was accurate.

PMID- 7502723
TI  - Indications for brachytherapy for brain tumours.

PMID- 7502724
TI  - Interstitial irradiation of brain metastases.
AB  - Randomized studies have shown that survival in patients with single brain
      metastases is significantly higher after the combined treatment of surgical
      removal and whole-brain irradiation than after whole-brain radiation therapy
      alone. In patients with deep-seated lesions or those located in critical sites of
      the brain, as well as in cases in which the patient's general condition makes
      general anaesthesia difficult or impossible microsurgical resection usually
      cannot be performed or only with an increased surgical risk. Stereotactic
      radiosurgery, which can be done by means of convergent beam irradiation or by the
      implantation of highly loaded 125I seeds, provides an alternative to open
      procedures. In the following we report on our results using a stereotactic
      radiosurgical technique. A series of 20 treatments is presented, in which biopsy
      was performed and 125I seeds were implanted, both under stereotactic conditions
      in the same session. The 125I seeds were sealed in a teflon catheter, were left
      indwelling temporarily, and then removed after application of the prescribed
      radiation dose (6,000cGy at the tumour margin). There was only one recurrence in
      our series, complications occurred in only one patient by temporary aggravation
      of a pre-existing hemiparesis. Our results indicate that interstitial irradiation
      of brain metastases is a valuable, less stressful alternative to both open
      microsurgery as well as to stereotactic radiosurgical convergent beam
      irradiation.

PMID- 7502725
TI  - Optimization of dose distribution for LINAC based radiosurgery using elliptical
      collimators.
AB  - The use of non-circular collimators is considered on all or some of the arcs used
      for radiosurgery on a linear accelerator in order to obtain conformal dose
      distribution for non-spherical lesions using a single isocenter. An extension of
      software to allow for use of non-circular collimators and a mathematical
      optimization based on prescribed doses on the lesion surface and on points in
      normal tissue (critical structures) are presented. Tests of the optimization
      method on simulated cases indicate that several boosts from selected positions
      along the arcs, superimposed on an optimized arc configuration allows one to
      obtain a highly conformal dose distribution with simple elliptical inserts. The
      optimization method can be applied to any type of collimation and is particularly
      effective with variable dose-rate machines.

PMID- 7502726
TI  - A prototype device for linear accelerator-based extracranial radiosurgery.
AB  - A prototype frame for accurate stereotactic localization and linear accelerator
      (LINAC)-based treatment of extracranial targets was developed. The ECRSF is
      designed to employ either spinal or skeletal osseous fixation to immobilize the
      area of interest and then encircle the targeted region with a traditional
      orthogonal, three-axis system. A series of experiments (n = 5) with semi
      radiolucent calibration targets (n = 15) and computed tomography (CT) scanning
      using the EC showed that a mean localization error of 0.98 +/- 0.22 mm was
      obtainable in the last two and most accurate series of experiments with these
      targets (n = 8). Using the LINAC to irradiate these same targets demonstrated an
      overall radiation treatment accuracy ranging from 1.4 to 2.0 mm. This discrepancy
      between localization error and overall radiation treatment error can be explained
      by a lack of isocentricity of the LINAC treatment which is typically less than 1
      mm and can be as low as 0.5 mm. These data demonstrate that extracranial
      stereotactic radiosurgery is now technically feasible and that the accuracy of
      such treatment would be acceptable for clinical treatment.

PMID- 7502727
TI  - Stereotactic convergent beam radiosurgery versus stereotactic conformation beam
      radiotherapy.
AB  - By means of preliminary results in the treatment of patients with acoustic
      neurinoma the achievable accuracies, dose distributions and time consumption of
      stereotactic LINAC-based convergent beam radiosurgery are compared to those
      achieved with fractionated stereotactic conformation beam radiotherapy.
      Characteristics of both techniques are described. With the Tubingen radiosurgery
      system a good adaptation of the dose distribution to spherical or oval target
      volumes with a steep dose gradient was achieved, whereas homogeneity and
      adaptation of the dose distribution to irregularly shaped targets were better
      with the Heidelberg conformation technique. The mechanical accuracy of the
      Tubingen floorstand system was 0.3 mm +/- 0.2 mm, and that of the Heidelberg mask
      fixation system < 1 mm. Both methods require similar total treatment times. Nine
      patients were treated by the Tubingen radiosurgery system. The results are
      compared with 12 patients treated by conformation radiotherapy in Heidelberg. In
      both patient groups no further tumour growth occurred. Four of 9 single dose
      treated patients developed side-effects, such as temporary trigeminal and facial
      paraesthesia hearing deterioration and oedema. In contrast, patients treated by
      fractionated radiotherapy showed no side-effects. Relating to the short follow-up
      the results indicate that single dose application has certain drawbacks for
      special indications. Further studies have to work out which method gives the best
      treatment results.

PMID- 7502728
TI  - Intra-operative marking of neuroanatomical details--helpful for radiosurgery?
AB  - This report is a list of simple but effective techniques for marking important
      structures intra-operatively. During the last 2 years in 52 patients intra
      operative marking techniques have been used. In 37 cases a small piece of fat has
      been taken. In 10 patients it was done by a radiopaque Barium impregnated silicon
      sphere and in 5 patients with a piece of a monofilament suture. Postoperative
      checks were done by conventional X-ray, computer tomography and Magnetic
      Resonance Imaging. The indication in all cases was to offer landmarks helpful for
      planning postoperative radiosurgery. In case of fat and radiopaque Barium
      impregnated silicone spheres the markings were always well defined and clear in
      contrast. In those cases where a piece of monofilament suture was used it was
      impossible to get clear postoperative information. In general there were no intra
      or post-operative complications. All markers were well tolerated and no side
      effects have been observed so far. The advantages and disadvantages of each of
      these possibilities are described and discussed.

PMID- 7502729
TI  - Frameless stereotaxy for radiosurgical planning and follow-up.
AB  - In our centre, 111 patients have been treated with linear accelerator
      stereotactic radiosurgery. Angiographic, CT and MRI images are generated and the
      target coordinates calculated in 3 dimensions. For CT scanning, cross sections of
      perpendicular and oblique fiducial markers are seen. For follow-up CT scans done
      without the frame, a virtual frame is generated by means of a computer program
      that places fiducial markers on each CT scan cut, as if the patient had been
      wearing the OBT frame and the scan produced with the gantry parallel to the base
      of the frame. The position of the oblique marker may be calculated by knowing the
      thickness and position of each CT cut. Various natural fiducial markers (bony
      landmarks) are identified by coordinates in the scan with the patient wearing the
      real frame and in the scan with the virtual frame applied. A transformation
      matrix is utilized to establish the equivalence between the original CT scan with
      the real frame applied and subsequent scans without the real frame but with the
      virtual frame applied. In effect, the virtual frame is re-applied in exactly the
      same position as the real frame. Lesion measurements may then be duplicated and
      growth or regression accurately established. The uncertainty in this system of re
      application resides in possible patient movement, CT scan slice thickness and
      inter-observer error in the identification of natural fiducial markers.

PMID- 7502731
TI  - Radiosurgery in the treatment of cerebral AVMs.
AB  - Radiosurgery of AVM's is gaining in popularity and is advocated by many for the
      treatment of lesions less than 3 cm in diameter. During a 17 month period 33
      patients with cerebral AVM's were treated with radiosurgery. All regions of the
      brain were represented in the series including brain stem. A mean follow-up of
      10.8 months revealed a 6% rebleed rate and a 9% total complication rate.
      Multimodality therapy including embolization and surgery is recommended for the
      treatment of AVM's and radiosurgery is seen as an important adjunctive treatment
      option.

PMID- 7502730
TI  - Stereotactic radiotherapy for AVMs: the University of Toronto experience.
AB  - Since July 1989, 66 patients have received stereotactic radiosurgery for
      arteriovenous malformations of the brain. All cases were reviewed by our
      multidisciplinary group. As result of our treatment algorithms these patients
      underwent stereotactic radiosurgery, either as the sole therapy or as part of
      combined modality treatment. Using a 6 MV linear accelerator, we have usually
      employed doses of either 15 or 20 Gy to the edge of the lesion, ensuring that
      critical normal structures do not receive a dose in excess of 15 Gy. Of the
      initial 24 patients followed for a minimum of 2 years, 12 have complete
      obliteration documented by angiography; 8 have > 90% obliteration (several have
      deferred further angiographic follow-up which may show progression to complete
      obliteration); 3 have had the nidus diminish; and one has had no change. Within
      this cohort, one patient experienced a transient acute effect; one patient has
      developed a minor late effect; one suffered a fatal hemorrhage despite ongoing
      response to radiosurgery; one has recently undergone retreatment.

PMID- 7502732
TI  - Treatment of symptomatic AOVMs with radiosurgery.
AB  - In spite of great success in the treatment cerebral AVMs with stereotactic
      radiosurgery, the role of this treatment modality in angiographically occult
      vascular malformations (AOVMs) is not recognized. Since the installation of the
      Gamma-knife, we have treated 20 cases of AOVMs by radiosurgery. There were 13
      males and 7 females, the age ranged from 3 to 58 years with an average age of
      34.0 years. Their clinical presentations at the onset were haemorrhage in 11,
      convulsive seizure in 7 and progressive neurological deficits in 2. Two cases had
      multiple lesions. Among 20 symptomatic lesions, 14 were located supratentorially,
      4 in the brain stem and 2 in the cerebellar hemispheres. Following localization
      with MRI and dose planning, the lesions were treated by radiosurgery and the
      doses ranged from 15 to 20 Gy at the margins. Follow-up studies indicate a
      significant control of rebleeding as well as of the convulsive seizure. Imaging
      studies demonstrated the shrinkage of the lesion in 3 and reduced enhancement
      with Gadolinium-DTPA in some others. Adverse effects, chiefly related to
      radiation-induced oedema, occurred in 5. But they were generally mild and well
      controlled by medication. Thus the preliminary results indicate a certain
      usefulness of radiosurgery in the treatment of symptomatic AOVMs.

PMID- 7502733
TI  - Microsurgery versus radiosurgery in the treatment of small acoustic neurinomas.
AB  - Microsurgical preservation of the facial nerve during removal of acoustic
      neurinomas can hardly be compared with microsurgery of the eighth cranial nerve.
      Many more anatomical and pathogenetic factors are involved that need careful
      consideration. In small neurinomas, of grades I and II, total extirpation of the
      tumour with preservation of both the facial nerve and segments of the
      vestibulocochlear nerve not directly involved by the tumour has become a safe and
      practical technique. In small acoustic neurinomas immediate facial nerve function
      could be preserved in 88% and "useful hearing" could be preserved in 78%. A
      number of different types of tumour-cranial nerve relationships could be
      established in small acoustic neurinomas, showing also the effects of adjusted
      surgical techniques on the preservation of hearing. Optimal selective separation
      of cranial nerves from the tumour is only possible through open surgical
      intervention, while radiosurgery requires the irradiation of the entire
      tumour/nerve complex.

PMID- 7502734
TI  - The need for adjunctive focused radiation therapy in pituitary adenomas.
AB  - In pituitary adenomas radiation therapy regardless of the technique should be
      limited to surgical failures. The delayed onset of beneficial effects and the
      high rate of pituitary insufficiency have to be weighed against the good surgical
      and/or medical results in the treatment of these tumours. Unfortunately surgical
      outcome is almost invariably correlated with invasive growth. Invasiveness is
      statistically significantly correlated with tumour size, as well as with high
      proliferation rates, which can be measured by immunohistological methods such as
      mAB KI-67. Owing to the good results of medical treatment, radiation therapy is
      usually unnecessary in prolactinomas. Patients with persistent hypersecretion of
      growth hormone after unsuccessful surgery may represent the ideal candidates for
      radiation therapy, whereas patients with persistent Cushing's disease need cure
      for hypercortisolism without delay. In patients with residual tumour due to non
      functioning adenomas, radiation therapy should only be given if the proliferation
      rate is high.

PMID- 7502735
TI  - Gamma knife radiosurgery for metastatic brain tumors.
AB  - Sixty-three patients with metastatic brain tumors have had stereotactic
      radiosurgery 90 times with the Leksell Gamma Knife over a 29-month period.
      Initially, a single treatment of 35 to 45 Gy was delivered to the enhanced CT
      margin. This dose was found to be inadequate for tumor control. We then raised
      the marginal dose to 50 to 55 Gy, but even this radiosurgical dose did not appear
      to control tumor growth. However, we have found that metastatic brain tumors can
      be controlled successfully using enhanced MR scans and a peripheral dose of 60 Gy
      or even 65 Gy adjacent to the enhanced margins of the metastatic brain tumors,
      especially melanomas.

PMID- 7502736
TI  - Radiosurgery of the metastatic brain tumours with gamma-knife.
AB  - The results of treatment of metastatic brain tumours by radiosurgery are
      reported. Twenty cases including lung (11), colon (5), breast (1), ovary (1),
      liver cancer (1) and malignant melanoma (1) were involved. Seven cases had single
      and 13 had multiple brain metastases. In total 55 lesions were evaluated after
      radiosurgery with the gamma-knife. Following localization with MR1 and dose
      planning, radiosurgery with marginal doses between 12 to 25 Gy (mean 18.9 Gy) was
      delivered. In the follow-up studies with MRI after 3 months, 29 out of 55 (52.7%)
      lesions showed significant shrinkage. In contrast 25 showed either no change (17)
      or central necrosis (8), and one was enlarged. Thus the tumour control at 3
      months was 98.2%, and subsequently 96.6% at 6 months. Clinical symptoms and signs
      were improved in most cases, but were aggravated in four cases either by tumour
      recurrence or by radiation-induced oedema. Although the tumours treated with
      radiosurgery were well controlled, tumour recurrence in another sites occurred in
      4 case, of which 3 were treated by 2nd radiosurgery with 2 successful tumour
      control. Complications were generally mild and transient. In summary stereotactic
      radiosurgery is valuable new treatment not only for solitary metastases, but also
      for multiple or recurrent ones.

PMID- 7502737
TI  - The neuroradiologist's contribution to stereotactic neuro-radio-surgery.
AB  - This publication is literally the same paper (having the same title and image
      material) which was previously presented at the International Symposium on
      Stereotactic Neuro-Radio-Surgery (Vienna, October 1992). Any actual updating of
      the topic has been avoided for reasons of historical accuracy and in order to
      document the atmosphere of that symposium which was then dominated by the
      unfolding of a new technology of intracranial lesion treatment. The
      neuroradiologist's contribution to this modality of treatment has to be the
      imaging and localizing such lesions accurately, as well as advising colleagues
      who plan radiosurgery and warning them about possible pitfalls. If there is no
      close cooperation between radiosurgeons and neuroradiologists, or if
      neuroradiological assistance is even disregarded, radiosurgical activities may
      fail.

PMID- 7502738
TI  - The results of radiosurgical management of 139 single cerebral metastases.
AB  - Between March 1984 and June 1993, linac radiosurgery was performed in 139
      patients for single brain metastases, using the non-invasive (Greitz-Bergstrom)
      head fixation system. This atraumatic system was utilized for subsequent
      stereotactic CT/NMR staging to obtain strictly comparable neuro-imaging. Thus,
      tumour response was evaluated precisely and radiosurgery repeated (straight after
      the diagnostic sitting), as needed. No hospitalization or anaesthesia was
      necessary. The 25 mm target was the maximum size to avoid the risk of radiation
      induced reactions. In metastases exceeding this limit single doses were directed
      at more than one target at the same session. Focusing upon single or multiple
      targets was facilitated by 3-D stereotactic NMR. The results after one single
      sitting were compared with those obtained after staged sittings in the same
      patients. Radiosurgery achieved disappearance or shrinkage of the metastasis with
      resolution of the oedema and mid-line shift in 86% of the 139 patients treated.
      In 47% of them, however, the success was the result of repeat radiosurgery and
      staged sittings. The non-invasive procedure is the keystone to optimize the
      radiosurgical results.

PMID- 7502739
TI  - Infectivity by HIV-1 of human uterine endometrial carcinoma cells.

PMID- 7502740
TI  - IgA subclasses and molecular size in children with vertically transmitted HIV
      infection.

PMID- 7502741
TI  - Intestinal immune responsiveness in HIV-infected individuals.

PMID- 7502742
TI  - Loss of CD4 positive T cells and evidence for impaired differentiation of both
      CD4 and CD8 positive T cells in the large intestine of patients infected with
      human immunodeficiency virus (HIV). Berlin Diarrhea/Wasting Syndrome Study Group.

PMID- 7502743
TI  - Loss of activated CD4-positive T cells and increase in activated cytotoxic CD8
      positive T cells in the duodenum of patients infected with human immunodeficiency
      virus. Berlin Diarrhea/Wasting Syndrome Study Group.

PMID- 7502744
TI  - Biased T cell receptor V beta repertoire of intestinal CD8+ T cells in HIV
      disease.

PMID- 7502745
TI  - Neutralization of HIV infection by serum IgA antibodies.

PMID- 7502746
TI  - Whole and parotid saliva IgA and IgA-subclass responses to Candida albicans in
      HIV infection.

PMID- 7502747
TI  - Decreased IgA-producing cells in the gut of SIV-infected rhesus monkeys.

PMID- 7502748
TI  - Functional and phenotypic lymphocyte population changes in the mesenteric lymph
      nodes of murine-AIDS infected mice.

PMID- 7502749
TI  - Transport into rat bile of radiolabelled intravenous human polymeric IgA1 and
      IgA2, treated or not with neuraminidase.

PMID- 7502750
TI  - Hepatic elimination of circulating IgA immune complexes: a comparison between
      rats and guinea pigs.

PMID- 7502751
TI  - The involvement of Kupffer cells and liver endothelial cells in the clearance of
      large sized soluble IgA aggregates in rats.
AB  - These findings suggests that AIgA is bound both by KC and EC in normal
      situations. Because of the great phagocytic capacity of KC, the contribution of
      EC in handling AIgA in normal rats is minimal. However, when KC are defect or
      absent (as after Cl2MDP treatment), the handling of AIgA by EC may become of
      mayor importance, i.e. it will take over the phagocytic function of KC. Studies
      concerning a possible receptor on EC involved in binding of AIgA are in progress.

PMID- 7502752
TI  - Isolation and preliminary characterization of human mononuclear liver cells.

PMID- 7502753
TI  - IgA production and transport in the murine liver after mucosal immunization.

PMID- 7502754
TI  - Detection of IgA and its receptor in the exocrine pancreas and the extrahepatic
      bile duct of the rat.

PMID- 7502755
TI  - Multiple intraperitoneal injections of turkey serum cause a major enlargement of
      the biliary tree in BALB/c mice.

PMID- 7502756
TI  - Antibody binding to liver cells and cell differentiation state.

PMID- 7502757
TI  - Expression of interferon-gamma gene in the liver from patients with liver and
      gastrointestinal tract diseases.

PMID- 7502758
TI  - Tumour necrosis factor alpha--a constitutive protein of bile.

PMID- 7502759
TI  - Anti-parietal cell antibody in autoimmune liver diseases is associated with
      gastric mucosal atrophy and intestinal metaplasia.

PMID- 7502760
TI  - Cytokine gene expression in the liver.

PMID- 7502761
TI  - Intraepithelial lymphocytes expressing TCR gamma delta in human gingival tissues.

PMID- 7502762
TI  - Characterization of cytokine producing T cells, TCR expression, and IgA plasma
      cells in salivary gland-associated tissues.
AB  - In this study, SMG, PGLN, and CLN from murine SGAT were employed in order to
      understand immunological characteristics of mononuclear cells that reside in
      these tissues for IgA responses. Based on our results, SMG harbor characteristics
      of IgA effector tissues. Further, PGLN has immunological features of both IgA
      effector tissue and systemic LN. On the other hand, CLN possesses classical
      characteristics of an organized systemic LN. Several important and unique
      features of T cells in SMG were demonstrated by this study. For example,
      approximately 40-50% of MC in SMG were CD3+ T cells which consisted of an equal
      distribution of CD4+, CD8- and CD4-, CD8+ T cell subsets. This can be considered
      as a unique feature of SMG since the other effector tissues usually have 2 to 3
      times higher frequencies of CD4+ T cells over CD8+ T cells. Most interestingly,
      CD4-, CD8+ T cell subset contains both alpha beta TCR+ and gamma delta TCR+ T
      cells. Other than SMG, IELs possess significant number of gamma delta TCR bearing
      CD4-, CD8+ T cells. In terms of cytokine producing T cells, SMG contain
      significant numbers of CD4+ T cells which are capable of producing IL-5 and IFN
      gamma. In addition, higher numbers of IL-5 producing Th 2-type cells was always
      seen in SMG when compared with IFN-gamma secreting Th1-type cells. Therefore, the
      occurrence of predominant IgA producing cells is associated with the appearance
      of a higher frequency of IL-5 secreting Th 2-type cells.

PMID- 7502763
TI  - Local antibodies and cytokine responses in crevicular fluid of patients with
      juvenile periodontitis.

PMID- 7502764
TI  - Generation and distribution of antibody secreting cells in salivary glands of
      mice immunized with Porphyromonas gingivalis fimbriae.

PMID- 7502766
TI  - T-subsets and disturbed immunoregulation in patients with periodontal disease.

PMID- 7502765
TI  - Expression and immunogenicity of a cloned Porphyromonas gingivalis hemagglutinin
      in Salmonella typhimurium.

PMID- 7502767
TI  - Changes in neutrophil function in patients with early onset periodontitis
      according to family occurrence of the disease.

PMID- 7502769
TI  - Gamma/delta T lymphocytes in marginal periodontitis in patients with Down's
      syndrome.

PMID- 7502770
TI  - Peptide mapping and amino acid sequence analysis of the 40 kDa outer membrane
      protein of Fusobacterium nucleatum.

PMID- 7502768
TI  - VLA-4/VCAM-1 pathway in human periodontal disease.

PMID- 7502771
TI  - Development of salivary IgA antibody to oral streptococcal antigens associated
      with virulence.

PMID- 7502772
TI  - Dental caries and salivary anti-Streptococcus mutans antibodies in IgA deficient
      children.

PMID- 7502773
TI  - Differences in secretory IgA and serum antibodies to Streptococcus mutans
      isolates from caries-resistant and caries-susceptible subjects.

PMID- 7502774
TI  - Induction of salivary IgA responses to Streptococcus mutans antigen I/II after
      intranasal immunization.

PMID- 7502777
TI  - The concentrations of secretory immunoglobulin A and specific S-IgA antibodies in
      the saliva of school children.

PMID- 7502776
TI  - Lack of cross-reaction of antibodies against cell-associated glucosyltransferase
      from Streptococcus mutans with human heart tissue.

PMID- 7502775
TI  - Potential for glucosyltransferase-based synthetic peptides in a dental caries
      vaccine.

PMID- 7502778
TI  - Immunization against the oral indigenous bacteria of the BALB/c mouse.

PMID- 7502779
TI  - Oligosaccharides in mucosal host defense: model, method, and first data.

PMID- 7502780
TI  - Possible role of EBV in oral squamous cell carcinoma--EBV inhibits programmed
      cell death of squamous cells.

PMID- 7502781
TI  - Expression of ras-P21 in salivary gland tumors.

PMID- 7502782
TI  - Autoimmune reactions induced by gliadin.

PMID- 7502784
TI  - T-cell receptor V-gene usage in Sjogren's syndrome.

PMID- 7502783
TI  - Influence of androgen therapy on lacrimal autoimmune disease in a mouse model of
      Sjogren's syndrome.

PMID- 7502785
TI  - Preferential use of the VHIII immunoglobulin gene family for the synthesis of
      rheumatoid factors.

PMID- 7502786
TI  - Gene hypothesis of autoimmunity, and autoimmune disease.

PMID- 7502788
TI  - Oral tolerance in humans: T cell but not B cell tolerance to a soluble protein
      antigen.

PMID- 7502787
TI  - Treatment of autoimmune diseases by oral tolerance to autoantigens.

PMID- 7502789
TI  - Oral tolerance to ovalbumin in mice: effect of some parameters on the induction
      and persistence of the suppression of systemic IgE and IgG antibody responses.

PMID- 7502790
TI  - Evidence of a direct role for mucosal immune cells in the induction of oral
      tolerance.

PMID- 7502792
TI  - Specific immunological non-responsiveness induced by antigens via mucosal
      surfaces.

PMID- 7502791
TI  - The absence of gut flora has no effect on the induction of oral tolerance to
      ovalbumin.

PMID- 7502793
TI  - The influence of antigen digestion on orally induced immunity and tolerance.
AB  - 1. Pepsin-digested form of OVA has approximately the same molecular weight as
      native OVA, but differs in charge and isoelectric focusing point. 2. Pepsin
      treated OVA retains most of the native OVA T- and B-cell determinants. 3. Delayed
      type hypersensitivity response is suppressed when pepsin-treated OVA is
      administered i.p. to naive mice. 4. Cimetidine treatment of mice prior to
      ingestion of OVA shows decreased tolerance, while oral administration of pepsin
      treated OVA to cimetidine-treated mice leads to a complete immune
      unresponsiveness; this suggests an important role for gastric digestion in orally
      induced immune tolerance.

PMID- 7502794
TI  - Mucosal suppression by oral pre-treatment with ovalbumin and its conversion into
      stimulation when ovalbumin was conjugated to cholera toxin or its B subunit.

PMID- 7502796
TI  - The incidence of colonic natural killer cells, large granular lymphocytes and
      mast cells in inflammatory bowel disease.

PMID- 7502795
TI  - Exploitation of the whole gut lavage technique for in vivo assessment of
      intestinal immunity and inflammation in inflammatory bowel disease.

PMID- 7502797
TI  - Evidence for a regulatory "defect" for CD4 positive intestinal T cells in vitro
      in patients with IBD compared to normals.

PMID- 7502798
TI  - Epithelial deposits of immunoglobulin G1 and activated complement co-localize
      with the "M(r) 40kD" putative auto-antigen in ulcerative colitis.
AB  - In conclusion, the "M(r) 40kD" antigen is expressed on the apical face of colonic
      enterocytes often in spatial relation to immune complexes in active UC,
      apparently targeting an IgG1-mediated autoimmune attack. Thus, our findings
      support the notion that an autoimmune response to the "M(r) 40kD" antigen, with
      local production of specific IgG1, is a possible immunopathological mechanism(s)
      in UC.

PMID- 7502799
TI  - Immunoglobulin subclass distribution of anti-LPS antibody-secreting cells of
      colonic mucosa from patients with inflammatory bowel disease.

PMID- 7502800
TI  - Cell activation and proliferation in the large intestine of patients with Crohn's
      disease or ulcerative colitis and controls.

PMID- 7502802
TI  - Activation of lamina propria T lymphocytes in Crohn's disease.
AB  - Crohn's disease is characterized by chronic inflammatory infiltrates and
      granuloma formation in the gut. T cell directed immunotherapy appears to be
      effective in relieving these symptoms. Under normal conditions, lamina propria T
      lymphocytes have a low proliferative response to antigen receptor stimulation in
      vitro due to the influence of the local intestinal environment. This study shows
      that lamina propria T lymphocytes exhibit an enhanced response to antigen
      receptor stimulation in active Crohn's disease, which may contribute in its
      pathogenesis.

PMID- 7502801
TI  - Altered expression of T cell differentiation antigens in T cells isolated from
      the large intestine of patients with Crohn's disease or ulcerative colitis.

PMID- 7502803
TI  - Alterations in the cytotoxic activity of Crohn's disease peripheral blood T cells
      expressing different T-cell receptor variable gene products.

PMID- 7502804
TI  - In situ detection of interleukin-1 beta and interleukin 8 in biopsy specimens
      from patients with ulcerative colitis.

PMID- 7502805
TI  - Effects of mesalazine on the formation of lipoxygenase and cyclooxygenase
      products.

PMID- 7502806
TI  - Leukocyte-endothelial cell interactions: potential targets for mesalazine in
      Crohn's disease.

PMID- 7502807
TI  - P-ANCA as a differential diagnostic marker in inflammatory bowel disease.

PMID- 7502808
TI  - Antioxidant properties of 5-aminosalicylic acid: potential mechanism for its
      protective effect in ulcerative colitis.

PMID- 7502809
TI  - Interferon alpha-2A (roferon) as a treatment of inflammatory bowel disease in
      children and adolescents.

PMID- 7502810
TI  - Distribution and density of TNF immunoreactivity in chronic inflammatory bowel
      disease.

PMID- 7502811
TI  - 4D5.4, a monoclonal antibody which recognizes cells in inflamed human intestine.

PMID- 7502812
TI  - TCR gamma/delta + and CD8+TCR alpha/beta + intraepithelial lymphocytes (IEL)
      express proliferation marker (Ki-67) in the coeliac lesion.
AB  - In conclusion, it appears that gluten induces a non-proliferative activation of
      CD4+ lamina propria T cells, but a proliferative activation in the TCR alpha/beta
      +CD8+ and TCR gamma/delta + IEL subsets. Although the increased density of TCR
      alpha/beta +CD8+ and TCR gamma/delta + IEL in the coeliac lesion may be secondary
      to T cell mediated immune activation in the lamina propria, a direct and primary
      antigen-driven proliferation of IEL (perhaps CD1-dependent29) cannot be excluded.

PMID- 7502813
TI  - Analysis of marker genes contributing to coeliac disease susceptibility.

PMID- 7502814
TI  - Jejunal fluid antibodies and mucosal gamma/delta IEL in latent and potential
      coeliac disease.

PMID- 7502815
TI  - IgA subclass distribution of IgA anti-gliadin antibodies in feces of patients
      with coeliac disease.

PMID- 7502816
TI  - Soluble CD4 antigen is increased in active coeliac disease.

PMID- 7502817
TI  - The interaction of gliadin with effector and target cells in NK cell activity of
      patients with celiac disease.

PMID- 7502818
TI  - Crypt epithelial cells express the 4F2 antigen in untreated coeliac mucosa.

PMID- 7502820
TI  - Interaction of natural and synthetic peptides derived from gliadin with different
      cell lines.

PMID- 7502819
TI  - Short-term cultivation of duodenal biopsies in patients with coeliac disease.
      Effect of gluten challenge and gliadin peptides.

PMID- 7502821
TI  - Dose- and time-dependent ultrastructural and functional lesions of the colonic
      mucosa by Entamoeba histolytica lysates.

PMID- 7502823
TI  - Recurring viral pathology and immunological implications.

PMID- 7502822
TI  - Immunopathogenetic mechanisms in spondylarthropathy and gut inflammation.

PMID- 7502824
TI  - Immunological studies of the mucosa in colitis induced by sodium dextran sulfate
      in rats.

PMID- 7502825
TI  - Non-lymphoid cells in experimental inflammatory bowel disease.

PMID- 7502827
TI  - Oral mercuric chloride leads to intestinal basement membrane (IBM) immune complex
      deposition and fecal protein loss.

PMID- 7502826
TI  - Immunohistochemical study of rat Peyer's patches in peptidoglycan-polysaccharide
      complex-induced chronic enteritis.

PMID- 7502828
TI  - The role of nitric oxide in enteropathy.

PMID- 7502829
TI  - Induction of specific immunity at mucosal surfaces: prospects for vaccine
      development.
AB  - We have demonstrated the feasibility of studying antigen-specific immune
      responses in a variety of mucosal tissues in humans after vaccination and during
      infection. In this respect, we have documented the usefulness of both oral
      cholera and ETEC vaccines for assessing in functional terms specific
      subpopulations of B- and T-cell immunocytes during an immune response initiated
      and/or expressed in human mucosal tissues. Circulating specific IgA antibody
      secreting cells in blood appear to reflect recent or ongoing antigen exposure of
      mucosal surfaces. This implies that the detection of such cells in blood, the
      most accessible lymphoid compartment in humans, represents the simplest way to
      assess the immunogenicity of mucosal vaccines and to supplement the diagnostic
      and monitoring of active mucosal infections. Our studies indicate that while the
      concept of an integrated mucosal immune network is clearly operational in humans
      (at least in regards to induction of secretory antibody responses), its
      generalization appears somewhat simplistic as illustrated by the
      compartmentalization of immune responses initiated in certain mucosal organs such
      as the small intestine and the tonsils. Finally, the potential of the cholera
      toxin B subunit as a carrier for delivery of chemically or genetically linked
      foreign epitopes for induction of disseminated mucosal immune responses raises
      hope for the development of broadly applicable vaccines to control mucosal
      infections.

PMID- 7502830
TI  - Mucosal responsiveness as a determinant of protection mechanisms induced by oral
      immunization.

PMID- 7502831
TI  - Oral immunization studies with Streptococcus mutans and influenza vaccines in
      rhesus macaque monkeys.

PMID- 7502833
TI  - Do CD5 B cells respond to oral antigens?

PMID- 7502832
TI  - The antibody response in infants after oral administration of inactivated and
      living E. coli vaccines and their protective effect against nosocomial
      infections.

PMID- 7502834
TI  - Induction of specific antibody responses in the human nasopharyngeal mucosa.

PMID- 7502835
TI  - Phenotypic characterization of circulating antibody-secreting cells after mucosal
      and systemic immunizations in humans.
AB  - We have developed a simple approach for immunophenotyping of functional lymphoid
      cell subpopulations. Using this approach we have partly characterized circulating
      antigen-specific ASC after systemic versus mucosal immunization with respect to
      maturational and activation stages, and to their anatomic commitment(s).
      Comparative analyses of mucosally versus systemically activated circulating ASC
      reveal differences with respect not only to utilization of homing receptor
      molecules but also to certain activation markers, and especially cell surface MHC
      class II molecules. We have now extended these studies to several other markers
      including early and late B-cell maturation markers, and we are currently
      examining whether differential expression of HLA-DQ molecules on the majority of
      mucosally activated blood ASC may explain the relative inability of these cells
      to present soluble antigens to class II-restricted T-cells.

PMID- 7502836
TI  - Induction of CTL by oral immunization.

PMID- 7502837
TI  - Immunization by the enteral and respiratory route with viable and inactivated
      bacteria results in a differential increase in lymphocyte subsets in the
      bronchoalveolar space.

PMID- 7502838
TI  - Biodegradable microparticles as oral vaccines.

PMID- 7502839
TI  - Intraduodenal immunization with microencapsulated CFA/II induces a delayed, anti
      CFA/II, IgG antibody-secreting spleen cell response.

PMID- 7502840
TI  - Xenobiotic polymers as vaccine vehicles.

PMID- 7502841
TI  - Oral immunization with dehydrated liposomes containing Streptococcus mutans
      glucosyltransferase (GTF) in humans.

PMID- 7502842
TI  - Fluorescent labelling of virus, bacteria and iscoms: in vivo systemic and mucosal
      localisation patterns.

PMID- 7502843
TI  - Bioadhesive polymers for oral drug delivery.

PMID- 7502844
TI  - Presence of antigen-specific long-term memory cells in systemic lymphoid tissues
      as well as locally in the gut lamina propria following oral immunization with
      cholera toxin adjuvant.

PMID- 7502845
TI  - Cholera toxin enhances antigen presentation.

PMID- 7502846
TI  - Cholera toxin increases T lymphocyte responses to unrelated antigens.
AB  - We have found that CT adjuvant greatly augmented oral priming immunizations.
      Limiting dilution analysis revealed strong increases in the frequency of primed
      antigen specific T lymphocytes subsequent to the use of CT adjuvant. Moreover,
      several fold stronger lymphokine production accompanied the strong proliferative
      responses seen with CT-treated and KLH-primed T cells. The lymphokine pattern
      secreted by these T cells suggested that TH1 as well as TH2 types of cells were
      effectively primed by KLH, and that CT adjuvant did not exert a selective effect
      on any of these T-cell subsets. These effects of CT were truly due to
      immunomodulation and not simply the result of a more efficient uptake of gut
      luminal antigens in the presence of CT, because CT enhanced equally well T cell
      priming by peroral as well as parenteral immunization with KLH. Moreover, the CT
      induced enhanced responsiveness to antigen was also observed with CD4(+)-enriched
      T cells suggesting that CT primarily affected T cell priming rather than the
      balance between CD4+ and CD8+ T cell subsets.

PMID- 7502847
TI  - Molecular engineering of cholera toxin.

PMID- 7502848
TI  - Effect of cholera toxin and its B subunit on intestinal permeability for
      ovalbumin.

PMID- 7502849
TI  - Cholera and pertussis toxins, but not forskolin or LT-B, adjuvant IgA antibody
      responses to orally administered antigen.

PMID- 7502850
TI  - The kinetics of an intestinal immune response.

PMID- 7502851
TI  - Cholera toxin-mediated cellular immune responses against ovalbumin administered
      orally.

PMID- 7502852
TI  - Induction of transmissible gastroenteritis coronavirus specific immune responses
      using vectors with enteric tropism.

PMID- 7502854
TI  - Lactobacilli: vehicles for antigen delivery to the female urogenital tract.

PMID- 7502853
TI  - Expression and stability of herpes simplex virus antigens in Salmonella
      typhimurium.

PMID- 7502855
TI  - New and safe "oral" live vaccines based on lactobacillus.

PMID- 7502856
TI  - Mucosal and systemic responses following enteric exposure to lactic acid
      bacteria.

PMID- 7502857
TI  - Specific antibody-producing cells in humans after oral immunization with a
      ribosomal vaccine Ribomunyl.

PMID- 7502858
TI  - Induction of IgA and IgG antibodies in vaginal fluid, serum and saliva following
      immunization of genital and gut associated lymphoid tissue.
AB  - Vaginal immunization with the Simian immunodeficiency virus (SIV) was
      investigated in macaques in order to study genital mucosal antibodies. A combined
      route of genital- and gut-associated lymphoid tissues was used to stimulate IgA
      and IgG antibodies in vaginal fluid, serum and saliva. Macaques were immunized
      with a recombinant, particulate SIV antigen (SIV gag P27), covalently linked to
      the mucosal adjuvant cholera toxin B subunit (CTB). The animals were immunized
      sequentially as follows: vaginal (x2) followed by oral (x3), or the reverse
      sequence of immunization. The results show that both vaginal followed by oral
      immunization or the reverse sequence induces specific p27 IgA and IgG antibodies
      in the vaginal fluid and serum. IgA antibodies were also detected in saliva.
      Vaginal IgA antibodies have the secretory component and J chain suggesting that
      they are of secretory origin.

PMID- 7502859
TI  - T cell responses in macaques after vaginal immunization with particulate SIV p27
      antigen.
AB  - Rhesus monkeys were immunized by the vaginal and oral routes using a recombinant
      particulate simian immunodeficiency virus (SIV) antigen. Augmenting vaginal by
      oral immunization in macaques elicits proliferative CD4+ T cells in the
      circulation which are specific to the immunizing p27 antigen. Reconstitution of
      enriched CD4+ T cells, B cells and macrophages from circulating mononuclear cells
      help B cells in specific IgA anti-p27 antibody synthesis. The results suggest
      that augmented vaginal immunization induces systemic CD4+ T and B cell responses
      which may play a part in the protective immunity against SIV (HIV) infection.

PMID- 7502861
TI  - Ig-secreting and interferon-gamma-producing cells in mice mucosally immunized
      with influenza virus.
AB  - 1. Oral immunization of mice with influenza virus type A/Udorn, induced antigen
      specific IgA antibodies in external secretions (e.g., saliva and fecal extract).
      2. Increased numbers of antigen-specific IgA spot-forming cells (SFC) were seen
      in mononuclear cells isolated from IgA-effector tissues (e.g., SG) of mice orally
      immunized with influenza virus. 3. Following oral or systemic immunization of
      mice, IFN gamma-secreting cells (Th1 type) displayed a characteristic pattern of
      distribution which was related to the route of immunization.

PMID- 7502860
TI  - Mucosal immunization with a recombinant adenovirus vector induces local and
      systemic immunity and protection from herpes simplex virus.

PMID- 7502862
TI  - Cell-mediated immunity in owl monkeys following inoculation with hepatitis A
      virus.

PMID- 7502864
TI  - Anti-HSV-1 herpes vaccination by LUPIDON H: preliminary results.

PMID- 7502863
TI  - Oral immunization against respiratory viruses in mice.
AB  - The results presented here extend our previous observations regarding oral
      immunization against respiratory viruses in three areas. First, from an
      experiment comparing Sendai virus with influenza virus it appears that the nature
      of the antigen as well as host-parasite interactions may play an important role
      in efficiency of oral immunization. Second, oral immunization with an inactivated
      virus can apparently induce a cell-mediated immune response. Preliminary evidence
      (not shown) indicated that the magnitude of effector cell killing versus virus
      infected target cells was positively influenced by including cholera toxin in the
      oral immunization regimen. This is consistent with a recent report that cholera
      toxin could enhance T cell proliferative response to co-fed KLH. Finally, we have
      shown that oral immunization with inactivated virus plus cholera toxin combined
      with intranasal inactivated virus boosting, can protect mice from infection for
      nearly two years--their normal life span.

PMID- 7502865
TI  - Nasopharyngeal and systemic humoral responses induced by trivalent attenuated
      poliomyelitis vaccine in newborns.

PMID- 7502866
TI  - Mucosal and systemic immunization with pneumococcal polysaccharide type 3, 4 and
      14 in the rat.

PMID- 7502867
TI  - Aerosol treatment of pigs with Actinobacillus pleuropneumoniae serotype 2:
      mucosal immunity and resistance against challenge.

PMID- 7502868
TI  - Immunity to aerosolized staphylococcal enterotoxin B.

PMID- 7502869
TI  - Comparative study of bronchoalveolar lavages in normal subjects and in patients
      with chronic pulmonary obstructive disease.

PMID- 7502870
TI  - Oral vaccines against cholera and enterotoxigenic Escherichia coli diarrhea.

PMID- 7502871
TI  - Impaired mucosal immune response in vitamin A deficient rats immunized with oral
      cholera vaccine.

PMID- 7502872
TI  - Why do we not yet have a suitable vaccine against cholera?
AB  - The available options, past and present, of cholera vaccines have been summarized
      above. It is saddening but clear that, more than a century after the introduction
      of the first cholera vaccine, we still do not have available a suitable vaccine
      against cholera. The currently raging and expanding new epidemic of cholera in
      the Western hemisphere dramatically illustrates anew the need, although a new
      illustration is not necessary if one but considers the innumerable, but
      unnecessary, victims of cholera of the past which could have been prevented had a
      suitable vaccine been available earlier. Indeed, it should also be clear from
      this review that a suitable vaccine against cholera still eludes us and will for
      an additional period of time. Cholera, a disease of humans only, can be
      controlled by prevention of human to human transmission, i.e., by universal
      availability of appropriate sewage disposal and clean water--an expensive
      solution, but one which will also reduce the toll of the other diseases
      transmitted by the fecal-oral route. Short of this, we should not be diverted by
      less than a highly effective, and economical vaccine. The "bottleneck" resides in
      the difficulty of getting from the laboratory to the field: the essential, and
      most efficient, intermediate step being the testing of candidate vaccines in
      volunteers--laboratory animal models do not suffice. Cholera is now, especially
      under controlled conditions, a perfectly treatable disease. Additional volunteer
      centers, and studies in volunteers, are essential to the solution of the cholera
      problem in the near future.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7502873
TI  - Vaccine-specific T cells in human peripheral blood after oral immunization with
      an inactivated enterotoxigenic Escherichia coli vaccine.

PMID- 7502875
TI  - Impairment of immunogenicity of Salmonella typhi Ty21a due to pre-existing cross
      reacting intestinal antibodies.

PMID- 7502874
TI  - Oral immunization induces humoral and cell-mediated immunity and protects germ
      free mice against infection from Helicobacter felis.

PMID- 7502876
TI  - Assessment of attenuated Salmonella typhimurium strains designed as potential
      carriers of foreign antigens for mucosal localization and immuno-genicity in a
      rabbit model.
AB  - Neither wild type nor attenuated S. typhimurium strains induced diarrheal illness
      in rabbits. All strains localized to the Peyer's patch at higher concentrations
      than in lumenal contents or adjacent ileum. Wild type S. typhimurium C5 induced a
      typhoid-like illness in rabbits with severe weight loss, bacteremia, persistent
      splenic colonization, and serum IgG response. Both attenuated strains were
      disseminated to spleen (day 3) but produced minimal systemic illness. They
      induced biliary IgA responses greater than the wild type (day 7), but minimal
      serum IgG responses. Both mutants of S. typhimurium are suitable for further
      development as live enteric vaccines to carry foreign antigens since they
      localize to Peyer's patch after oral inoculation, induce biliary antibody, and
      produce minimal systemic disease. The attenuated strains tested are systemically
      disseminated. It remains to be determined whether dissemination (determined by a
      large virulence plasmid) is necessary for the desired mucosal immune response or
      acceptable for an oral vaccine strain.

PMID- 7502877
TI  - Humoral immune response against Salmonella typhimurium antigen fractions and
      protection.

PMID- 7502878
TI  - Oral immunization against mucosal candidiasis in a mouse model.

PMID- 7502879
TI  - Evidence for a generalized signaling abnormality in B cells from patients with
      common variable immunodeficiency.

PMID- 7502880
TI  - Defects of the intestinal humoral immune system in common variable
      immunodeficiency syndrome.

PMID- 7502881
TI  - Incidence of primary immunodeficiencies in a population of south Moravia,
      Czechoslovakia.

PMID- 7502882
TI  - Aberrations in titer and avidity of serum IgM and IgG antibodies to microbial and
      food antigens in IgA deficiency.

PMID- 7502883
TI  - Immunological study of children with IgA deficiency.

PMID- 7502884
TI  - Development, function, and trafficking of mucosal leukocytes in immunodeficient
      mice.

PMID- 7502885
TI  - Rearrangement of RAG-1 recombinase gene in DNA-repair deficient/immunodeficient
      "wasted" mice.

PMID- 7502886
TI  - T lymphocytes subpopulations in the intestinal villi of immune deficient rats.

PMID- 7502887
TI  - Comparison of the local immune response to nontypable Haemophilus influenzae
      (nHI) and Moraxella catarrhalis (MC) during otitis media.

PMID- 7502888
TI  - Immunological effects of tonsillectomy/adenectomy in children.

PMID- 7502889
TI  - Tonsillar lymphocyte subsets in tonsillitis and hyperplasia.

PMID- 7502890
TI  - A study of lymphocyte adherence to middle ear mucosal tissue.

PMID- 7502891
TI  - An animal model to study the mechanisms of immunity induced in the respiratory
      tract by intestinal immunization.

PMID- 7502892
TI  - Immunity to respiratory Pseudomonas aeruginosa infection: P. aeruginosa-specific
      T cells arising after intestinal immunization.

PMID- 7502893
TI  - Immunity to Pseudomonas aeruginosa induced by OprF following intestinal
      immunization.

PMID- 7502894
TI  - The protective role of pulmonary neutrophils in rats intestinally immunized with
      Pseudomonas aeruginosa.

PMID- 7502895
TI  - Immunity to respiratory Pseudomonas aeruginosa infection: the role of gut-derived
      T helper cells and immune serum.

PMID- 7502896
TI  - Secretory IgA against pertussis toxin and surface structures of Bordetella
      pertussis in saliva of children with culture proven pertussis.

PMID- 7502897
TI  - Alteration of cytokine secretion and cytotoxicity of murine alveolar macrophages
      after in vitro infection with respiratory syncytial virus (RSV).

PMID- 7502898
TI  - Local specific immunization and non-specific stimulation of the defense
      mechanisms of the respiratory tract of swine.

PMID- 7502899
TI  - Assessment of the clinical value of using an immunomodulator in recurrent
      respiratory infections.

PMID- 7502900
TI  - Reduction of the number and severity of respiratory tract infections in children
      by oral immunostimulation.

PMID- 7502901
TI  - Oral immunization with lung-pathogenic bacteria is protective against defined
      challenge in a pig aerosol infection model.

PMID- 7502902
TI  - Induction of immune responses in nasopharyngeal secretions after oral
      immunization with bacterial lysates.

PMID- 7502903
TI  - Use of gut lavage fluid to measure intestinal humoral immunity, GI bleeding and
      protein losses in Sierra Leonean children.

PMID- 7502904
TI  - Small intestinal biopsies characterized by lectin and actin labelling and
      confocal microscopy.

PMID- 7502905
TI  - TNF alpha secreting cells in normal and diseased human intestine.

PMID- 7502906
TI  - Lymphocyte subpopulations in gut-associated lymphoid tissue of cattle with
      experimental mucosal disease.

PMID- 7502907
TI  - Clonal antibody dominance after influenza vaccination in IgA nephropathy patients
      and controls.

PMID- 7502909
TI  - Study of intestinal permeability in IgA mesangial nephritis and primary
      glomerulonephritis.

PMID- 7502908
TI  - Study of salivary and serum secretory IgA in IgA mesangial nephritis and primary
      glomerulonephritis.

PMID- 7502910
TI  - IgE heterogeneity and biological activity.

PMID- 7502911
TI  - Immediate nasal response to allergen challenge cytologic changes in the nasal
      secretions and histologic changes in the nasal mucosa.

PMID- 7502913
TI  - The significance of transient mucosal IgA deficiency on the development of asthma
      and atopy in children.

PMID- 7502915
TI  - CD23/FC epsilon RII is constitutively expressed on human intestinal epithelium,
      and upregulated in cow's milk protein intolerance.

PMID- 7502912
TI  - Late nasal response to allergen challenge cytologic changes in the nasal
      secretions and histologic changes in the nasal mucosa.

PMID- 7502914
TI  - Hypersensitivity to soybean proteins in early weaned piglets: humoral and
      cellular components.

PMID- 7502916
TI  - Two-dimensional analysis of cow's milk allergens with the IPG-DALT technique.

PMID- 7502917
TI  - Cow's milk allergy: the humoral immune response to eight purified allergens.

PMID- 7502918
TI  - Regional small intestinal passage in the rat to some commonly used permeability
      probes.

PMID- 7502919
TI  - Intestinal passage of 51Cr-EDTA and ovalbumin in the rat with intra-abdominal
      sepsis.

PMID- 7502920
TI  - Chemosensitive afferent nerves in the regulation of gastric blood flow and
      protection.
AB  - The experimental use of capsaicin has made possible the discovery that
      chemosensitive neurons participate in the activation of endogenous mechanisms of
      protection in the face of pending injury to the gastric mucosa. At present, the
      pathophysiological potential of this neural emergency system is best reflected by
      the gastric hyperemic response to acid back-diffusion, a response which is
      signalled to a large degree by peptidergic afferent neurons. There is good
      evidence that CGRP released from perivascular afferent nerve endings is an
      important mediator of the acid-induced hyperemia in the rat gastric mucosa. The
      vasodilator action of CGRP depends on the formation of NO which functions as a
      second intercellular messenger of the CGRP- induced vasodilatation. The resulting
      hyperemia acts to limit acid damage to the superficial part of the mucosa. The
      hyperemic and protective roles of peptidergic sensory neurons have been studied
      in most detail in the stomach but there is evidence that they play a similar role
      in the esophagus, duodenum and colon. Further elucidation of this neural
      emergency system in the digestive system represents an important area for studies
      into the pathophysiology and management of gastrointestinal mucosal damage.

PMID- 7502921
TI  - Immunophenotyping of hematological neoplasms. I. Expression of progenitor cell
      surface antigen (CD34).

PMID- 7502922
TI  - The gene for familial Mediterranean fever is mapped to 16p 13.3- p13.1 with
      evidence for homogeneity.

PMID- 7502923
TI  - Comparison of the effects of sulphasalazine, 5-aminosalicylic acid and
      sulphapyridine on the humoral response to antigen in vivo.

PMID- 7502924
TI  - Adult T cell leukemia-derived factor as an endogenous radical scavenger.

PMID- 7502925
TI  - Immune reaction of pigs following intra-gastric or ileal inoculation of
      attenuated Salmonella typhi.

PMID- 7502926
TI  - Mucosal immune response in patients with dysentery.

PMID- 7502928
TI  - Stomach lymphocytes in experimental Helicobacter infection.

PMID- 7502927
TI  - A monoclonal antibody to Shigella dysenteriae serotype 13 cross-reacting with
      Shiga toxin.

PMID- 7502929
TI  - Selective increase of CD4+ and CD25+ T cells but not of gamma delta T cells in H.
      pylori associated gastritis.

PMID- 7502930
TI  - Mucosal and serum IgA antibodies in pigs following infection with Actinobacillus
      pleuropneumoniae.

PMID- 7502931
TI  - Recognition of acidic proteins of Giardia muris by anti-trophozoite antibodies.

PMID- 7502932
TI  - Electrophysiologic and morphologic effects of Entamoeba histolytica lysates on
      rabbit colon.

PMID- 7502933
TI  - Specific antiamebic serum antibodies in Mexican puerperae and their newborns.

PMID- 7502934
TI  - The role of intra-epithelial and lamina propria leucocytes during infection with
      Eimeria tenella.

PMID- 7502935
TI  - Patterns of cytokine mRNA in Trichinella spiralis infected rats.

PMID- 7502936
TI  - Specific anti-E. histolytica IgA monoclonal antibodies.

PMID- 7502937
TI  - Immunopathological responses of DBA/2 mice to primary infections of the bile duct
      tapeworm, Hymenolepis microstoma and the effect of anthelmintic treatment.

PMID- 7502938
TI  - Cytokine regulation of intestinal mastocytosis in Nippostrongylus brasiliensis
      infection.

PMID- 7502939
TI  - Glycoconjugates in rat small intestinal mucosa during infection with the
      intestinal nematode Nippostrongylus brasiliensis.

PMID- 7502940
TI  - Cytokine response in the intestinal lamina propria of mice after infection with
      Fasciola hepatica.

PMID- 7502941
TI  - Egg-negative residents of an Opisthorchiasis-endemic area possess high levels of
      anti-Opisthorchis antibodies.

PMID- 7502942
TI  - The effect of T-cell mitogens and cytokines on the infectivity of human fallopian
      tube mucosa by Chlamydia trachomatis.

PMID- 7502943
TI  - Antibody secreting cells in upper urinary tract infection: comparison of the
      response in children and adults.

PMID- 7502944
TI  - Detection of hepatitis C virus (HCV)-RNA in saliva and gastric juice.

PMID- 7502945
TI  - Herpes- and corona-virus infection of rat lacrimal acinar cells.

PMID- 7502946
TI  - Parasite infections in Danish trout farms.
AB  - Samples from 5 Danish freshwater trout farms rearing rainbow trout (Oncorhynchus
      mykiss) were examined for parasite infections from October 1993 until November
      1994 and recorded parasites are listed. In addition, results from an examination
      of a mariculture net cage system are presented as well. A total of 10 metazoan
      and 10 protozoan parasites were recorded. The metazoans included Gyrodactylus
      derjavini, Gyrodactylus salaris, Eubothrium crassum, Triaenophorus nodulosus,
      Proteocephalus sp., Diplostomum spathaceum, Tylodelphus clavata and Argulus
      foliaceus from the freshwater farms. The protozoans Hexamita salmonis,
      Ichthyobodo necator, Ichthyophthirius multifiliis, Apiosoma sp., Epistylis sp.,
      Trichodina nigra, T. mutabilis, T. fultoni, Trichodinella epizootica, and an
      Ichthyophonus like intestinal parasite were also detected in the freshwater trout
      farms. Based on lectin binding studies, few fish were found positive for the
      myxosporean parasite PKX although no clinical cases were reported. In the
      mariculture system, Lepeophtheirus salmonis and Caligus elongatus were found.

PMID- 7502947
TI  - A checklist of metazoan parasites from rainbow trout (Oncorhynchus mykiss).
AB  - An extensive literature survey on metazoan parasites from rainbow trout
      Oncorhynchus mykiss has been conducted. The taxa Monogenea, Cestoda, Digenea,
      Nematoda, Acanthocephala, Crustacea and Hirudinea are covered. A total of 169
      taxonomic entities are recorded in rainbow trout worldwide although few of these
      may prove synonyms in future analyses of the parasite specimens. These records
      include Monogenea (15), Cestoda (27), Digenea (37), Nematoda (39), Acanthocephala
      (23), Crustacea (17), Mollusca (6) and Hirudinea (5). The large number of
      parasites in this salmonid reflects its cosmopolitan distribution.

PMID- 7502948
TI  - Anoplocephala perfoliata in horses in Sweden: prevalence, infection levels and
      intestinal lesions.
AB  - Distal ileum, caecum and proximal colon of 470 horses were examined for helminths
      during 1 year at an abattoir in central Sweden. The infection levels of the horse
      tapeworm Anoplocephala perfoliata, their stage of development, site of attachment
      and gross pathological lesions caused by the worm were recorded. Faecal samples
      from 395 of the horses were examined specifically for tapeworm segments and eggs
      in order to correlate these findings with the numbers in the alimentary canal. In
      total 65% of the horses were infected with A. perfoliata and the mean intensity
      of infection was 79 worms per infected horse with a maximum of 912. The level of
      infection was significantly higher in (1) 3rd and 4th than in 1st and 2nd quarter
      of the year; (2) older horses than in yearlings; (3) females than in males and
      geldings; (4) thoroughbred and cold-blooded horses than in Swedish standard
      breeds and ponies. The level of infection was unaffected by the usage of
      anthelminthics against nematodes. Of the horses examined 51% had 1-100 worms
      whereas 14% were infected with more than 100 worms. Of the tapeworm positive
      horses 72% had mixed infections with both adult and juvenile worms, 20% solely
      juveniles, and 8% solely adults. The severity of intestinal lesions exacerbated
      by increasing numbers of A. perfoliata. About 11% of the intestines examined had
      severe lesions, but there was no history of acute abdominal distress in any of
      the horses included in this study. Although the number of detectable eggs was
      significantly higher for horses heavily infected with A. perfoliata, the egg
      recovery among infected horses was only 35%. An additional field survey
      comprising 218 horses on 88 premises in central and southern parts of Sweden
      showed that the prevalence of A. perfoliata egg positive horses was the same as
      found on faecal examination during the abattoir survey.

PMID- 7502949
TI  - Calcification of intervertebral discs in the dachshund: a radiographic study of
      21 stud-dogs.
AB  - The vertebral columns of 21 clinically normal, 4.9 to 13.2 year old dachshunds
      were x-rayed. This sample represented 55.3% of all male dachshunds with 20 or
      more offspring registered with the Norwegian Kennel Club in the period 1985-1989.
      Calcified intervertebral discs were identified in 9 (42.9%) of the stud-dogs, and
      the number of calcified discs in each individual varied from 2 to 5 with a mean
      of 3.7. The frequency of stud-dogs with 1 or more calcified discs was compared
      with the corresponding frequency in a material of 327 one-year-old dachshunds. In
      this comparison, the relative risk was estimated with 95% confidence bounds. When
      the different composition of size and coat varieties in the 2 materials was not
      considered, the relative risk of calcified discs was found to be 1.77 (0.99-3.2)
      times higher in stud-dogs than in young dogs. When the different composition of
      varieties in the 2 materials was considered, the relative risk was found to be
      1.9 (1.1-3.4) times higher in stud-dogs than in young dogs. The results of the
      present study strongly suggest that an increase in the frequency of dachshunds
      with 1 or more calcified intervertebral discs occurs after 1 year of age.

PMID- 7502950
TI  - Antimicrobial susceptibility and rRNA gene restriction patterns among
      Staphylococcus intermedius from healthy dogs and from dogs suffering from
      pyoderma or otitis externa.
AB  - A total of 60 Staphylococcus intermedius strains from dogs were investigated by
      their sensitivity to various antibiotics (50 strains) and by their rRNA gene
      restriction patterns (ribotyping) (60 strains). Fifteen isolates were from
      healthy dogs, 9 with otitis externa, and 36 with pyoderma, including 10 strains
      from a previous study. Sixty per cent of the 50 strains tested for antibiotic
      susceptibility demonstrated resistance to penicillin, 24% to spiramycin, 20% to
      tetracycline, 16% to chloramphenicol, and 2% to fucidic acid. All isolates were
      susceptible to amoxycillin with clavulanic acid, enrofloxacin, and sulphonamides
      with trimethoprim. There were no significant differences in antimicrobial
      susceptibility patterns observed among isolates from pyoderma, otitis externa or
      healthy dogs. Among the 60 strains studied by ribotyping, 10 different ribotypes
      were identified: 6 different ribotypes among isolates from otitis externa, 8
      among isolates from pyoderma, and 5 among isolates from healthy dogs. One
      ribotype (profile C) was dominant among the isolates from healthy dogs while
      another ribotype (profile A) was dominant among strains from dogs suffering from
      pyoderma. This profile was not demonstrated in any of the strains from healthy
      dogs. From 5 different dogs suffering from pyoderma, 2 different clones were
      demonstrated based on their plasmid profile and antibiogram. In these dogs 1 of
      the clones always belonged to ribotype A. The results concerning strains of S.
      intermedius isolated from furunculosis suggest the existence of distinct
      subpopulations with different pathogenicity to dogs.

PMID- 7502951
TI  - Effects of calf removal at parturition on postpartum ovarian activity in Zebu
      (Bos indicus) cows in the humid tropics.
AB  - To assess endocrine and morphological responses of ovaries to total weaning at
      parturition, 6 Zebu (Bos indicus) cows 5 years or older were investigated.
      Following parturition, blood samples were collected daily during the first month
      and twice weekly thereafter until day 60 to determine concentrations of
      progesterone (P4) and prostaglandin F2 alpha metabolite. It took between 25 to 32
      days to complete uterine involution. The prostaglandin metabolite remained
      elevated for a mean period of 14.2 days (range, 4-21) postpartum. Five of the
      animals resumed cyclicity with a short estrous cycle starting between days 7 to
      34 and lasting between 7 and 14 days. No estrous behavior was recorded prior to
      the short estrous cycles, but subsequent normal-length estrous cycles were all
      preceded by signs of estrus. In the 1 animal that resumed cyclicity with an
      estrous cycle of normal length on day 37 (length 20 days), the cycle was preceded
      by estrous behavior. Progesterone concentrations reached a mean maximum of 4.8
      nmol liter-1 during the short estrous cycles, and prostaglandin metabolite
      concentrations peaked while P4 concentrations were decreasing. P4 concentrations
      reached a mean maximum of 12.2 nmol liter-1 during the estrous cycles of normal
      length. The interval from parturition to the first estrous cycle of normal length
      varied between 16 and 48 days, and the length of the cycle was 18 to 22 days.
      Starting 2 days postpartum, ovaries from 5 of the cows were scanned by
      ultrasonography every second day until day 30 postpartum. Medium-sized follicles
      were detected between days 4 to 7 postpartum in 4 of the scanned cows that later
      had short estrous cycles. The time between parturition and the appearance of the
      first dominant follicle was 7.6 days (range 6-10 days). The interval between
      parturition and the appearance of the first ovulatory-sized follicle was 10.2
      days (range 8-13 days). In 3 of the scanned cows this ovulatory-sized follicle
      ovulated. We conclude that cyclic ovarian activity in Zebu cows can start early
      in the postpartum period in the absence of offspring, and that short luteal
      phases, not preceded by estrous behavior, may play an important role in
      establishing normal postpartum ovarian activity.

PMID- 7502952
TI  - Some factors influencing pregnancy rate and subsequent litter size in primiparous
      sows.
AB  - The pregnancy rate and the subsequent litter size were studied in 332 Swedish
      Yorkshire primiparous sows, fed according to a commercial Swedish feeding regime
      during lactation. The sows were weighed and backfat depth was recorded at the
      first farrowing, at weaning, and at mating. Oestrous detection was performed once
      daily after weaning, and the interval from weaning to first oestrus (IWO) was
      recorded. Blood samples for determination of plasma progesterone were drawn
      regularly after the first weaning. Statistical analyses were only performed on
      sows with an IWO of 3-8 days. Of these 206 sows were mated on their first (OE1
      sows) and 87 sows on their second (87 OE2 sows) oestrus after weaning. The
      pregnancy rate was 85.4% for OE1 sows and 75.9% for OE2 sows (p = 0.048). There
      was no significant difference in pregnancy rate between OE1 sows with an IWO of 3
      5 days and OE1 sows with an interval of 6-8 days. OE2 sows with an IWO of 6-8
      days, on the other hand, had a significantly lower pregnancy rate compared with
      OE2 sows with an interval of 3-5 days. The pregnancy rate in sows that lost more
      than 30 kg during the first lactation period did not differ from that of sows
      losing less than 30 kg. In sows with a first litter size of more than 9 piglets
      alive at birth, the pregnancy rate decreases significantly if mating is delayed
      until the second oestrus after weaning. OE2 sows had a significantly larger
      second litter size at birth than OE1 sows (+2.0). The litter size at six weeks
      did not, on the other hand, differ significantly (+0.4). There was a positive
      correlation between the IWO and 2nd litter size, although significant only for
      OE1 sows between the IWO and litter size alive at birth. In the OE1 group, sows
      losing 20 kg or less during lactation had significantly larger second litters at
      birth than the sows losing 21-30 kg, but not significantly larger than the sows
      losing more than 30 kg. One piglet more, at birth, in the first litter resulted
      in 0.25 piglet more in the second litter. For sows with a large first litter
      there was a low probability of also having a large second litter.

PMID- 7502953
TI  - Heterologous radioimmunoassay for llama and alpaca luteinizing hormone with a
      monoclonal antibody, an equine standard and a human tracer.
AB  - A radioimmunoassay for llama and alpaca LH was developed using a human I125LH
      tracer from a commercial kit, equine LH diluted in human LH free serum as
      standard, and a monoclonal antibody (518B7) specific for LH but with low species
      specificity. A 60-min delay in the addition of the tracer and overnight
      incubation gave a sensitivity of 0.8 microgram L-1. The intra-assay coefficient
      of variation was 37% at 1 microgram L-1, declined to 15% at 4 micrograms L-1 and
      was below 6% for concentrations up to 32 micrograms L-1. The inter-assay
      coefficients of variation for 3 control samples were 20% (2.8 micrograms L-1),
      16% (7.1 micrograms L-1) and 9.8% (19 micrograms L-1). In an attempt to increase
      sensitivity, all tubes were preincubated for 4 h at room temperature before
      adding the tracer, and the sample volume was increased from 50 microL to 100
      microL (in the standard curve the increased volume was compensated for by human
      LH free serum). With this protocol, the assay sensitivity was 0.5 microgram L-1.
      The assay was validated clinically and demonstrated increased concentrations of
      LH after mating in llamas and alpacas. Furthermore, the assay was used to monitor
      LH responses to a single dose of GnRH in llamas (adult males and females at
      different ages).

PMID- 7502954
TI  - Ovarian activity at naturally attained oestrus in the sow. An ultrasonographic
      and LH study.
AB  - In 6 multiparous crossbred sows (2nd to 4th parity, Swedish Landrace x Swedish
      Yorkshire), 15 proosestrous-oestrous periods during 2 oestrous cycles were
      studied after weaning. The animals were controlled for oestrus, and the
      follicular growth and ovulation in their ovaries were followed by transrectal
      ultrasonography. Blood was sampled through indwelling catheters for analyses of
      LH and progesterone (P4). The duration of oestrus (standing reflex) was 47 +/-
      12.4 h, and the interval from onset of standing reflex until the end of ovulation
      was 39 +/- 12.4 h (range 20-64 h). The LH peak concentration was 3.7 +/- 0.8
      microgram/l, and the interval from LH peak level until ovulation was 23 +/- 8.4 h
      (range 8-32 h). The onset of standing reflex occurred in average 13 h before the
      LH peak level (range -4 - +36 h). The peripheral plasma concentration of P4
      showed a normal cyclic pattern in all animals. Low levels (mean levels, 1.1-1.3
      nmol/l) were seen during prooestrus and oestrus, high mean levels were found on
      days 10-16 (45-75 nmol/l) in the oestrous cycle. It was concluded that for an
      accurate determination of ovulation, each animal has to be examined repeatedly.
      Ultrasonography is a most valuable tool for this purpose.

PMID- 7502955
TI  - Influence of early season moxidectin treatments on acquisition of immunity to
      Ostertagia ostertagi in calves.

PMID- 7502956
TI  - Neospora caninum infection in a litter of Labrador retriever dogs in Denmark.

PMID- 7502958
TI  - Evaluation of the circle of Willis with three-dimensional CT angiography in
      patients with suspected intracranial aneurysms.
AB  - PURPOSE: To determine the usefulness of CT angiography in the setting of
      suspected acute subarachnoid hemorrhage or intracranial aneurysm. METHODS: We
      prospectively studied 68 patients suspected of having subarachnoid hemorrhage or
      an intracranial aneurysm with noncontrast CT of the head followed immediately by
      contrast-enhanced helical CT of the circle of Willis with three-dimensional
      reconstruction. Twenty-seven patients with CT findings positive for subarachnoid
      hemorrhage or intracranial aneurysm were evaluated with digital subtraction
      angiography or MR angiography within 12 hours of CT angiography. Patients with
      negative CT/CT angiography findings were followed up with lumbar puncture.
      RESULTS: CT angiography showed 23 of 24 aneurysms and 2 of 2 arteriovenous
      malformations (sensitivity, 96%; specificity, 100%). Aneurysm size ranged from 2
      to 40 mm (mean, 7.9 mm). Interobserver variability was 10%. In the 23 cases of
      subarachnoid hemorrhage, cisternal blood did not limit the three-dimensional
      reconstruction. Two patients with aneurysms on CT angiography had normal
      noncontrast scans. CONCLUSIONS: CT angiography of the circle of Willis is a
      useful technique for evaluation of suspected acute subarachnoid hemorrhage and
      intracranial aneurysm. It provides anatomic display of intracranial aneurysms,
      allowing for planning of conventional angiography and surgical approach. In
      selected cases, CT angiography may eliminate the need for preoperative
      conventional angiography.

PMID- 7502957
TI  - Radiation injury of the brain.
AB  - The clinical, radiologic, and pathologic findings in radiation injury of the
      brain are reviewed. Late radiation injury is the major, dose-limiting
      complication of brain irradiation and occurs in two forms, focal and diffuse,
      which differ significantly in clinical and radiologic features. Focal and diffuse
      injuries both include a wide spectrum of abnormalities, from subclinical changes
      detectable only by MR imaging to overt brain necrosis. Asymptomatic focal edema
      is commonly seen on CT and MR following focal or large-volume irradiation. Focal
      necrosis has the CT and MR characteristics of a mass lesion, with clinical
      evidence of focal neurologic abnormality and raised intracranial pressure.
      Microscopically, the lesion shows characteristic vascular changes and white
      matter pathology ranging from demyelination to coagulative necrosis. Diffuse
      radiation injury is characterized by periventricular decrease in attenuation of
      CT and increased signal on proton-density and T2-weighted MR images. Most
      patients are asymptomatic. When clinical manifestations occur, impairment of
      mental function is the most prominent feature. Pathologic findings in focal and
      diffuse radiation necrosis are similar. Necrotizing leukoencephalopathy is the
      form of diffuse white matter injury that follows chemotherapy, with or without
      irradiation. Vascular disease is less prominent and the latent period is shorter
      than in diffuse radiation injury; radiologic findings and clinical manifestations
      are similar. Late radiation injury of large arteries is an occasional cause of
      postradiation cerebral injury, and cerebral atrophy and mineralizing
      microangiopathy are common radiologic findings of uncertain clinical
      significance. Functional imaging by positron emission tomography can
      differentiate recurrent tumor from focal radiation necrosis with positive and
      negative predictive values for tumor of 80-90%. Positron emission tomography of
      the blood-brain barrier, glucose metabolism, and blood flow, together with MR
      imaging, have demonstrated some of the pathophsiology of late radiation necrosis.
      Focal glucose hypometabolism on positron emissin tomography in irradiated
      patients may have prognostic significance for subsequent development of
      clinically evident radiation necrosis.

PMID- 7502959
TI  - CT-defined large subcortical infarcts: correlation of location with site of
      cerebrovascular occlusive disease.
AB  - PURPOSE: To correlate the location of large subcortical infarcts with the site of
      cerebrovascular occlusive disease. METHODS: We examined CT and angiographic
      findings of 38 patients with major arterial occlusive disease and newly developed
      large subcortical infarcts of 2.0 cm or more, which were classified into three
      types: striatocapsular infarcts in the basal ganglia, terminal supply area
      infarcts in the corona radiata, and terminal supply area infarcts in the centrum
      semiovale. RESULTS: Two or three of the types of infarct were sometimes combined;
      the combination of the striatocapsular and corona radiata infarcts was the most
      frequent (14 [36.8%] of 38). Thirty-four (89.5%) had atherosclerotic major
      arterial occlusive diseases; 22 (57.9%) had occlusive diseases of the internal
      carotid artery, and 12 (31.6%) had diseases of the middle cerebral artery. The
      other 4 (10.5%) had embolic transient middle cerebral artery occlusion. Middle
      cerebral artery occlusive diseases frequently produced striatocapsular (13
      [81.3%] of 16) and corona radiata (13 [81.3%] of 16) infarcts but never induced
      the centrum semiovale lesions. On the other hand, in patients with internal
      carotid artery occlusive disease, the centrum semiovale (16 [72.7%] of 22) was
      more susceptible to ischemia than the striatocapsular region (11 [50%] of 22) or
      the corona radiata (9 [40.9%] of 22). CONCLUSIONS: Middle cerebral artery
      occlusive diseases frequently produced striatocapsular and/or corona radiata
      infarcts but never induced the centrum semiovale lesions, which were usually
      associated with internal carotid artery occlusive diseases.

PMID- 7502960
TI  - Parallel and spiral flow patterns of vertebral artery contributions to the
      basilar artery.
AB  - PURPOSE: To demonstrate that the in vivo flow from individual vertebral arteries
      can be imaged and tracked in the basilar artery by use of saturation planes with
      three-dimensional time of flight MR angiography. METHODS: Twenty volunteers were
      studied with intracranial three-dimensional time of flight angiography MR. The MR
      angiography was repeated with saturation of the individual vertebral arteries.
      Flow voids and signal intensity within the basilar and posterior cerebral
      arteries were evaluated for flow patterns. RESULTS: Of 15 volunteers with a
      "normal" vertebrobasilar anatomy, 80% demonstrated a pattern of flow within the
      basilar artery in which the contributing vertebral components remained
      ipisilateral. This pattern was called "parallel." A "spiral" pattern of rotation
      of the contributing vertebral components was found in 20% of studies. The inflow
      to the posterior cerebral arteries could be identified from specific vertebral
      contributions and was related to the size-dominance of the vertebral artery.
      CONCLUSION: There is nonadmixture of vertebral artery flows of variable duration
      within the basilar artery; at least two patterns of flow can be described within
      the basilar artery. The method presented is a simple technique for determining
      vertebral artery flow components with routine software and without secondary data
      manipulation.

PMID- 7502962
TI  - Radiating pain to the lower extremities caused by lumbar disk rupture without
      spinal nerve root involvement.
AB  - PURPOSE: To locate the origin of the pain during lumbar diskography by means of a
      limited intradiskal injection of a local anesthetic. METHODS: Lumbar diskography
      by the direct central posterior approach was performed in 235 consecutive
      patients. In 17 patients, severe and persistent low back pain, with unilateral or
      bilateral radiation to the lower extremities, was provoked by contrast injection
      into only one disk. One milliliter of 1% lidocaine was then slowly injected in
      the center of these disks. RESULTS: A 75% to 100% reduction of the low back pain
      was experienced by 13 patients, and a 75% to 100% reduction of the radiating pain
      was experienced by 16 patients within 60 seconds after the intradiskal injection
      of lidocaine. Radiographs demonstrated radial tears through the entire annulus
      thickness in 16 of 17 disks. CONCLUSION: Our results suggest that, in some
      patients with low back pain and unilateral or bilateral radiation to the lower
      extremities, the pain arises from within the disk. In these cases, pain radiating
      to the lower limb seems to be a referred type and seems unrelated to direct nerve
      root compression or irritation by a disk fragment in the epidural space.

PMID- 7502961
TI  - Characterization of intracranial mass lesions with in vivo proton MR
      spectroscopy.
AB  - PURPOSE: To assess the use of in vivo proton MR spectroscopy for characterization
      of intracranial mass lesions and to ascertain its reliability in grading of
      gliomas. METHODS: One hundred twenty patients with intracranial masses were
      subjected to volume selective spectroscopy using stimulated echo acquisition mode
      (echo time, 20 and 270 milliseconds) and spin echo (echo time, 135 milliseconds)
      sequences. The intracranial lesions were grouped into intraaxial and extraaxial,
      as judged with MR imaging. Assignment of resonances was confirmed in two samples
      each of brain abscess, epidermoid cyst, and tuberculoma using ex vivo high
      resolution MR spectroscopy. RESULTS: The in vivo spectra appeared distinct
      compared with normal brain in all the cases. All high-grade gliomas (n = 37)
      showed high choline and low or absent N-acetyl-L-aspartate and creatine along
      with lipid and/or lactate, whereas low-grade gliomas (n = 23) were characterized
      by low N-acetyl-aspartate and creatine and high choline and presence of only
      lactate. N-acetyl-aspartate/choline ratio was significantly lower and
      choline/creatine ratio was significantly higher in high-grade gliomas than in low
      grade gliomas. Presence of lipids suggested a higher grade of malignancy. All
      metastases (n = 7) showed lipid and lactate, whereas choline was visible in only
      four cases. Epidermoids showed resonances from lactate and an unassigned
      resonance at 1.8 ppm. Meningiomas could be differentiated from schwannomas by the
      presence of alanine in the former. Among the infective masses, pyogenic abscesses
      (n = 6) showed resonances only from cytosolic amino acids, lactate, alanine, and
      acetate; and tuberculomas (n = 11) showed only lipid resonances. CONCLUSIONS: In
      vivo proton MR spectroscopy, helps in tissue characterization of intracranial
      mass lesions. Spectroscopy is a reliable technique for grading of gliomas when N
      acetyl-aspartate/choline and choline/creatine ratios and presence of lipids are
      used in combination.

PMID- 7502963
TI  - Bilateral retrosomatic clefts at multiple lumbar levels.
AB  - Low back pain developed in a 44-year-old woman with a history of rheumatoid
      arthritis. Radiographs of the lumbar spine revealed bilateral pedicle defects at
      L-3, L-4, and L-5, with widening of the spinal canal and spondylolisthesis of L-5
      on S-1. CT more clearly demonstrated bilateral retrosomatic clefts at multiple
      levels.

PMID- 7502964
TI  - Use of transcranial cerebral oximetry to monitor regional cerebral oxygen
      saturation during neuroendovascular procedures.
AB  - Using transcranial cerebral oximetry, we monitored 30 patients who underwent
      cerebral angiography by the femoral route. Transcranial cerebral oximetry is a
      noninvasive technique of regional cerebral oxygen saturation measurement that
      uses near-infrared spectroscopy to differentiate oxyhemoglobin from reduced
      hemoglobin. Needle puncture, catheterization, and contrast media injection
      produced no significant peak changes in saturation from baseline. Acute and
      persistent decreases in oxygen saturation were associated with vascular
      complications and were detected before development of clinical symptoms. Greater
      changes in saturation were observed during several neuroendovascular procedures,
      indicating the development of complications, signaling a need to stop further
      endovascular manipulation.

PMID- 7502965
TI  - Fistula of the posterior communicating artery and cavernous sinus.
AB  - A 24-year-old man was admitted with conjunctival hyperemia of the left eye and
      progressive chemosis and proptosis 1 month after a head injury. An angiogram
      showed an arterial-cavernous sinus fistula of the posterior communicating artery,
      which was treated with minicoils. The atypical configuration, transvenous
      embolization, and unusual nature of the communication suggested that
      communication developed through a newly generated vessel in granulation tissue.

PMID- 7502966
TI  - Acquired carotid-cavernous fistula caused by traumatic intracavernous rupture of
      an embryonic anastomosis.
AB  - This case of traumatic carotid-cavernous fistula was caused by rupture of a
      peculiar ipsilateral intracavernous anastomosis between the accessory meningeal
      artery and the redundant deep recurrent ophthalmic artery. In the opposite
      cavernous sinus there was an obvious anastomosis between the accessory meningeal
      artery and the ophthalmic artery, probably located in the lateral part of the
      cavernous sinus. The patient was successfully treated with transarterial
      embolization followed by surgery of the cavernous sinus. In light of the vascular
      embryology, it is possible that unusual embryonic connections between the
      primitive dorsal ophthalmic artery and the accessory meningeal artery already
      existed in both cavernous sinus areas.

PMID- 7502967
TI  - Isolated cerebral intraaxial varix.
AB  - A case of isolated parenchymal venous varix not seen on angiography is reported.
      CT demonstrated a well-defined cystic lesion with peripheral enhancement deep
      within the left temporal lobe. MR demonstrated a high-signal-intensity lesion
      with hemosiderin rim.

PMID- 7502968
TI  - Electrocorticographic evaluation of iobitridol, a nonionic contrast medium,
      during selective cerebral arteriography in rabbits.
AB  - PURPOSE: To study the effects of iobitridol, a nonionic contrast medium, on the
      electrocorticography and the blood-brain barrier structure in rabbits. METHODS:
      Iobitridol was compared with isoosmolar mannitol and isotonic saline after
      selective injection (2.5 mL per rabbit in 30 seconds) into the internal carotid
      artery in the rabbit (six per group). The electrocorticograms (two
      frontooccipital leads) were then subjected to spectral analysis (fast Fourier
      transform). Evans blue dye served as a marker of blood-brain barrier damage.
      RESULTS: No blood-brain barrier damage was found, regardless of the treatment
      administered. Selective catheterization induced an increase in slow waves (0 to 4
      Hz). Analyzed both spectrally (distribution of frequency bands, position of the
      maximum peak with respect to the distribution, and cerebral electric power) and
      conventionally, iobitridol did not modify the electrocorticograph parameters in
      the animals. This also applied to the mannitol and saline solutions. CONCLUSION:
      No chemotoxic effects of iobitridol were found.

PMID- 7502969
TI  - White matter changes caused by chronic solvent abuse.
AB  - PURPOSE: To examine the brain damage of solvent abusers in Japan, where pure
      industrial toluene is frequently abused. METHODS: Twenty solvent abusers 17 to 33
      years of age with 7.2 +/- 4.0 years of abuse were examined with a 1.5-T MR
      imaging system. RESULTS: White matter hyperintensities in cerebrum, brain stem,
      and cerebellum on T2-weighted images were found in seven cases. The extent of
      white matter change was most clearly shown on proton density-weighted images. The
      patients with restricted white matter change and intermediate white matter change
      showed white matter hyperintensities in the brain stem and cerebellum on T2
      weighted images, in some cases, with additional hypointensities in the
      corresponding T1-weighted images. These patients had mainly abused pure toluene.
      The patients with diffuse white matter change showed obvious brain atrophy,
      including hippocampal atrophy and thinning of the corpus callosum. These patients
      had mainly abused lacquer thinner. CONCLUSION: There are some patients with
      restricted but severe enough change to cause the neurologic symptoms in specific
      regions, such as the brain stem and/or cerebellum, before the brain atrophy
      becomes apparent. This suggests that the restricted white matter change
      represents not only an early change of diffuse white matter change, but at least
      in some cases also represents a qualitatively different change than that of
      diffuse white matter change. We suggest that pure toluene has a possible relation
      to this qualitative difference.

PMID- 7502970
TI  - Angiographic demonstration of reversible cerebral vasospasm in porphyric
      encephalopathy.

PMID- 7502971
TI  - Radiologic-pathologic correlation. Cerebral toxoplasmosis and lymphoma in AIDS.

PMID- 7502972
TI  - MR of oculomotor nerve palsy.
AB  - PURPOSE: To assess the utility of MR in third cranial nerve palsy. METHODS: We
      reviewed precontrast and postcontrast MR of 50 patients with third cranial nerve
      palsy. RESULTS: MR demonstrated an appropriate lesion in 32 cases. Of these
      patients, 6 had brain stem lesions and 15 had involvement of the nerve in the
      cavernous sinus; lesions of the cisternal segment of the nerve were present in 11
      patients, with enhancement of this segment observed in 9 patients. An
      inflammatory or infiltrative source of the palsy was indicated in 19 of these 32
      cases. Of 7 patients with pupillary involvement suggestive clinically of a
      compressive lesion, 4 demonstrated thickening and enhancement consistent with an
      infiltrative lesion of the nerve. Eighteen patients with pupil-sparing third
      cranial nerve palsies and a history of diabetes or vascular disease had normal MR
      findings, with no enhancement of the third cranial nerve observed. CONCLUSIONS:
      Patients who do not have a history of diabetes or hypertension and in whom a
      complete or incomplete third cranial nerve palsy develops with or without pupil
      sparing should undergo MR imaging initially (unless there are clear symptoms or
      signs of subarachnoid hemorrhage) to exclude the presence of an infiltrative
      lesion or intraparenchymal process. Patients who have a history of vascular
      disease and a clinical presentation that is suggestive of an ischemic event may
      be observed initially, but should undergo imaging if improvement does not occur
      within 3 months.

PMID- 7502973
TI  - MR of malignant optic glioma of adulthood.
AB  - A case of malignant optic glioma of adulthood is imaged in its early and late
      stages with high-resolution MR. The images show the mass to arise from the right
      optic nerve before invasion of the optic chiasm.

PMID- 7502974
TI  - MR of the cerebral operculum: topographic identification and measurement of
      interopercular distances in healthy infants and children.
AB  - PURPOSE: To evaluate the role of axial, coronal, and sagittal MR in
      identification of surface landmarks of the cerebral operculum and to determine
      the reference values of interopercular distances of each hemisphere in healthy
      infants and children on MR images. METHODS: Two hundred fourteen cerebral
      opercula of 35 healthy infants and 72 healthy children were retrospectively
      evaluated from 107 routine MR brain examinations. The surface landmarks of the
      operculum and interopercular distances of each hemisphere, which were
      subjectively divided into anterior interopercular distance (anterior sylvian
      width) and posterior interopercular distance (posterior sylvian width), were
      recorded from axial, coronal, and sagittal MR images, respectively. The mean
      value of anterior interopercular distance of each hemisphere was obtained by
      averaging two linear measurements of the anterior sylvian width from lateral,
      sagittal, and axial planes of the same side. Likewise, the posterior
      interopercular distance of each side of the brain was obtained from averaging of
      two measurements on lateral, sagittal, and coronal planes. RESULTS: The landmarks
      of the operculum were best identified by sagittal MR, followed by axial and
      coronal images. The average values of left anterior interopercular distance,
      right anterior interopercular distance, left posterior interopercular distance,
      and right posterior interopercular distance in infants were 1.9 +/- 1.3, 1.6 +/-
      1.1, 0.4 +/- 0.7, and 0.2 +/- 0.4 mm, and in children, 0.9 +/- 1.3, 1.0 +/- 1.4,
      0.03 +/- 0.23, and 0.01 +/- 0.07 mm, respectively. Infants showed significantly
      wider interopercular distances than children. Left anterior interopercular
      distance was significantly wider than right in infants, but not in children. Male
      children displayed a more significant increase in anterior interopercular
      distance than did female children. There was no statistic difference in
      measurements of anterior interopercular distance and posterior interopercular
      distance between female and male infants. CONCLUSIONS: The operculum should be
      evaluated with MR in three planes. Infants may show conspicuous sylvian fissures
      that should not exceed 4.5 mm (mean + 2 SD) anteriorly on axial and sagittal
      planes and 1.8 mm posteriorly on sagittal and coronal planes. Healthy children
      who have fully developed opercula should have an anterior interopercular distance
      of no more than 3.5 mm and a posterior interopercular distance of 0.5 mm.

PMID- 7502975
TI  - Altered vertebrobasilar flow in children: angiographic, MR, and MR angiographic
      findings.
AB  - PURPOSE: To characterize the clinical, MR, MR angiographic, and conventional
      angiographic findings in vertebrobasilar disease in children. METHODS: Eight
      children with posterior circulation ischemia and infarction had conventional spin
      echo MR and MR angiography of the head and neck. Six patients had conventional
      angiography. RESULTS: Six patients had alteration of vertebral or basilar artery
      flow void on spin-echo images. MR angiography showed all six cases of
      angiographically proved vertebrobasilar dissection or occlusion despite
      overestimating the extent of arterial abnormality in two patients. In two
      patients the intracranial peripheral branch cutoff shown at angiography was
      correctly predicted on screening MR angiography. CONCLUSION: Posterior
      circulation infarction in children is usually secondary to traumatic injury to
      the vertebrobasilar circulation. MR and MR angiography noninvasively show
      vertebrobasilar flow disturbances and compare favorably with angiography in
      documenting dissection or occlusion of the vertebrobasilar circulation. MR
      angiography may obviate the need for invasive angiography in these children at
      diagnosis and during follow-up of anticoagulation therapy.

PMID- 7502976
TI  - CT and MR appearance of otolaryngologic packing materials.
AB  - PURPOSE: To examine the CT and MR appearances of four packing materials commonly
      used in otolaryngologic surgery. METHODS: The CT and MR appearances of bismuth
      and iodoform paraffin paste, aqueous betadine gauze, calcium sodium alginate, and
      triadocortyl cream were examined. CT attenuation values were measured using
      phantoms containing packing materials. MR characteristics were examined by
      packing the external auditory meati of volunteers. Two illustrative case reports
      also are presented. RESULTS: Bismuth and iodoform paraffin paste has a high CT
      attenuation (> 3000 Hounsfield units) resulting in severe image degradation
      attributable to streak artifact. Aqueous betadine gauze was of high attenuation
      (258 Hounsfield units; SD, 16.5) but did not cause image degradation. The
      attenuation values of calcium sodium alginate and triadocortyl creme coincided
      with those of muscle and fat, respectively. On MR, calcium sodium alginate and
      bismuth and iodoform paraffin paste had imaging characteristics similar to muscle
      and aqueous betadine gauze had appearances similar to bone marrow. Triadocortyl
      cream had a high signal equal to that of fat on T1-weighted images but a lower
      signal similar to bone marrow on T2-weighted images. CONCLUSIONS: The presence of
      bismuth and iodoform paraffin paste can give rise to clinically important image
      degradation on CT. More seriously, residual packing material may be
      misinterpreted as infection or tissue necrosis.

PMID- 7502977
TI  - High-resolution CT of mastoid sinus pneumocele with external auditory canal
      stenosis.
AB  - A 34-year-old man presented with tinnitus and conductive hearing loss. CT
      demonstrated an expansile, air-containing cavity contiguous with mastoid air
      cells, narrowing the external auditory canal. This is a case of symptomatic
      pneumocele resulting in an air collection beneath external canal lining, possibly
      related to an abnormality in mastoid fusion.

PMID- 7502978
TI  - The hypoglossal canal: normal MR enhancement pattern.
AB  - PURPOSE: To review the anatomy of the hypoglossal canal and present the normal
      precontrast and postcontrast MR appearance of axial posterior fossa images.
      METHODS: Thirty-one axial MR examinations of the normal posterior fossa were
      retrospectively reviewed. RESULTS: The hypoglossal canals are well seen on 3-mm
      thick axial MR images of the posterior fossa (28 [90%] of 31 patients). Symmetric
      intense intracanalicular enhancement after intravenous administration of
      gadopentetate dimeglumine is routine, typically with minor anterior extension
      into the nasopharyngeal region (28 [100%] of 28). A linear filling defect
      traversing the enhanced canal often is seen (21 [75%] of 28) and may represent
      hypoglossal nerve rootlets. Circumferential enhancement of the meninges at the
      level of the foramen magnum was a common finding (19 [64%] of 28). CONCLUSION:
      Enhancement within the hypoglossal canal with anterior extension beneath the
      skull base is a normal finding. This pattern is characteristic enough on MR
      imaging to aid interpretation of skull base lesions and to exclude the
      possibility of a mass within the hypoglossal canal.

PMID- 7502979
TI  - Spontaneous involution of optic pathway lesions in neurofibromatosis type 1:
      serial contrast MR evaluation.
AB  - PURPOSE: To evaluate with contrast MR the evolution in size, signal, and contrast
      enhancement of optic pathway lesions in four patients with neurofibromatosis type
      1. METHODS: The four reported patients are children with ages ranging from 21
      months to 13 years affected by neurofibromatosis type 1 and optic pathway
      lesions. No treatment of the optic pathway lesions was carried out in these
      patients. They have been followed by serial contrast MR. RESULTS: In all patients
      a change in size, signal, and enhancement of optic pathways lesions was noted
      with time, and in the last follow-up study a marked reduction in size and
      enhancement of optic pathway lesions was observed in all cases. CONCLUSIONS:
      Modification and regression of optic pathway lesions with spontaneous
      disappearance of the enhancement is demonstrated. This finding could have a
      crucial influence on the therapeutic approach of the optic pathway lesions.

PMID- 7502980
TI  - Atypical MR appearance of Lhermitte-Duclos disease with contrast enhancement.
AB  - A case of surgically confirmed Lhermitte-Duclos disease demonstrated contrast
      enhancement on MR. Histologic examination verified corresponding increased
      vascularity in the molecular layer and adjacent leptomeninges.

PMID- 7502981
TI  - MR evaluation of frontal sinus osteoplastic flaps with autogenous fat grafts.
AB  - PURPOSE: To investigate the MR findings in patients who have had osteoplastic
      frontal sinus flaps placed for inflammatory sinonasal disease. METHODS: The MR
      images of 13 patients who had improvement of symptoms after osteoplastic frontal
      sinus flap placement with fat autograft were prospectively evaluated for the
      presence of high intensity on T2-weighted scans, contrast enhancement, and
      replacement of frontal sinus fat by lower-signal soft tissue. All studies were
      performed on a 1.5-T unit using a 5-in round surface coil placed over the nasion.
      Sagittal T1-weighted, axial and coronal fast spin-echo T2-weighted, and
      precontrast and postcontrast axial and coronal T1-weighted images were obtained
      through the operative bed. The T2-weighted and postgadolinium sequences were done
      with a fat-suppression technique. RESULTS: Hyperintensity within the frontal
      sinuses on T2-weighted images and enhancement (peripherally and/or centrally
      where fat was replaced with soft tissue) were found to some degree in all
      patients. The degree of replacement of frontal sinus fat with soft tissue ranged
      from 4% to 85% (mean, 43%). Five patients with persistent symptoms had no
      distinguishing MR features when compared with asymptomatic patients. CONCLUSIONS:
      Although increased T2-weighted intensity, fat replacement, and enhancement are
      findings compatible with inflammation, these changes may be seen in patients who
      are asymptomatic after placement of osteoplastic frontal sinus flaps; they may
      represent the normal granulation process. MR findings after flap placement are
      nonspecific and have limited utility in distinguishing symptomatic patients with
      recurrent inflammatory disease from asymptomatic patients whose imaging findings
      are related to postoperative scar tissue.

PMID- 7502982
TI  - Cranial rhabdoid tumor with marginal tumor cystic component and extraaxial
      extension.
AB  - We report the radiologic findings in a case of primary central nervous system
      malignant rhabdoid tumor with a cystic marginal component in a 4-month-old
      infant. Marginal tumoral cysts are unusual in tumors other than
      esthesioneuroblastoma.

PMID- 7502983
TI  - Cervical thorium dioxide granuloma ('thorotrastoma').
AB  - An elderly woman had an expanding cervical mass that entrapped and compressed the
      adjacent cranial nerves, blood vessels, and muscles. The mass was dense on
      radiographs, extended from the skull base to low neck in the prevertebral and
      parapharyngeal tissues, and showed mixed intensity on MR. A previous direct
      carotid arteriogram with thorium dioxide as the contrast agent suggested the
      histologically proved diagnosis of a cervical thorium dioxide granuloma
      ("thorotrastoma").

PMID- 7502985
TI  - Seizure-induced transient hippocampal abnormalities on MR: correlation with
      positron emission tomography and electroencephalography.
AB  - We report transient focal abnormalities on MR in a patient having frequent
      electrographic seizures that were not obvious clinically. Marked mass effect
      (confirmed with volumetric studies) and abnormal T2 signal intensity in the right
      hippocampal region correlated with electroencephalographic ictal activity and
      with increased positron-emitting radiotracer uptake in the medial temporal lobe.
      The follow-up MR 2 months later, after electroencephalography findings
      normalized, revealed no hippocampal abnormalities.

PMID- 7502984
TI  - Carcinosarcoma of the salivary gland on CT.
AB  - Three cases of carcinosarcoma of the salivary gland, two in the submandibular
      gland, and one in the parotid, were investigated with CT and exhibited a variety
      of findings. The density of the tumors was lower than that of normal
      submandibular tissue. A calcification was found in one case. One case showed
      extensive lymphadenopathy. The parotid lesion had low central density with an
      enhancing margin.

PMID- 7502986
TI  - Cardiac sarcoma metastatic to the brain.

PMID- 7502987
TI  - Enhancing meningeal blood vessels masquerading as leptomeningeal spread of tumor
      in obstructive hydrocephalus.
AB  - MR showed an enhancing mass in the pineal region and hydrocephalus and
      leptomeningeal enhancement, thought to indicate pinealoblastoma with
      leptomeningeal spread. During resection there was no evidence of spread, and
      repeat MR showed no residual tumor or meningeal enhancement, so the patient was
      not treated for metastasis. Because there were no signs of leptomeningeal tumor 4
      months after surgery, the meningeal enhancement is thought to have been related
      to venous stasis secondary to obstructive hydrocephalus.

PMID- 7502988
TI  - Frequency of meningeal enhancement caused by lumbar puncture.

PMID- 7502989
TI  - Symmetric lesions of the subthalamic nuclei in mitochondrial encephalopathies: an
      almost distinctive Mark of Leigh disease with COX deficiency.

PMID- 7502990
TI  - Annotated bibliography.

PMID- 7502991
TI  - Women's health as a priority.
AB  - Funding for the NIH Women's Health Initiative is allocated by Congress on an
      annual basis. Since the 1994 elections, which dramatically changed the balance of
      power and priorities in the U.S. Congress, some individuals have voiced concern
      over the future of this project. Pharmacists can ensure that funding for this
      research continues by contacting their congressional representative to express
      their views directly. They can also join forces with other pharmacists through
      their national and state pharmacy associations. Law makers and persons
      responsible for funding decisions are interested in and responsive to the
      positions taken by professional groups. Pharmacists can improve the health of
      their female patients by encouraging them to make healthy lifestyle changes
      (e.g., stop smoking, exercise regularly, reduce fat intake, maintain recommended
      body weight, obtain a Pap test annually, have mammograms at recommended
      intervals, and perform monthly breast self-examinations). Pharmacists should urge
      women who might benefit from HRT to talk about it with their physicians.
      Pharmacists are a valuable source of information about the advantages and
      disadvantages of HRT. The exclusion of women from clinical and epidemiologic
      studies has left clinicians with inadequate information about the best approach
      to preventing and treating many women's health problems. During the past decade,
      the efforts of various individuals, government agencies, and professional
      organizations have brought about policy changes that broaden opportunities for
      inclusion of women in clinical trials as well as increased funding for women's
      health research. The Women's Health Initiative and other research currently being
      conducted will yield valuable information that can be used to improve the health
      of women.

PMID- 7502992
TI  - Development of a new qualitative test for fit testing respirators.
AB  - A new qualitative fit test was developed using Bitrex (Macfarland Smith Limited)
      as the test agent. It was validated by running a series of paired qualitative and
      quantitative fit tests. Quantitative tests were conducted with a small corn oil
      aerosol, using a condensation nucleus counter as a detector. Qualitative fit
      tests were run with Bitrex and saccharin, following the established protocol for
      the saccharin fit test. Four models of National Institute for Occupational Safety
      and Health--approved replaceable filter respirators were used in the study. All
      were half mask models equipped with high efficiency filters. In some cases,
      respirators expected to be the correct size for test subjects were tested. In
      other cases, respirators expected to be too small or too large for the subjects
      were tested. Test results were analyzed using fit test method validation criteria
      recommended in the American National Standards Institute draft standard on fit
      testing (ANSIZ88.10). The Bitrex and saccharin tests were found to have virtually
      identical performance. Both met proposed American National Standards Institute
      requirements for a valid qualitative fit test.

PMID- 7502993
TI  - A transient model of mass transfer and kinetics in a passive vapor sampler.
AB  - A transient model of vapor contaminant diffusion and homogeneous reaction in a
      two-compartment passive sampler was formulated. The mathematical analysis
      considered finite reaction kinetics, bulk air boundary-layer effects, and the
      solubility of the vapor contaminant in the liquid absorbing/reacting medium. The
      model was evaluated using experimentally measured Cl2 uptake rates in a series of
      samplers of different dimensions containing a 0.1% aqueous sulfamic acid solution
      in the absorbing medium chamber. The theory predicts accurately the effects of
      sampler diameter, stagnant air chamber path length, and sampler orientation with
      respect to the flowing air on Cl2 uptake, with an average error of less than 10%.
      Chlorine uptake in a 33-mm diameter sampler with a 10.8-mm path length was found
      to be essentially independent of wind direction and varied by approximately 23%
      for wind speeds ranging from 5.1 to 203 cm s-1 (10-400 ft min-1). Calculations
      show that the sampler is sensitive to wind speed partly because of the Cl2
      hydrolysis reaction, which produces HOCl and drops the vapor phase concentration
      of chlorine to near zero at the stagnant air/absorbing medium chamber interface,
      regardless of the rate of homogeneous reaction between HOCl and sulfamate anions.
      If the solubility of the vapor contaminant in the liquid absorbing medium were to
      obey Henry's Law (no hydrolysis reaction) and the homogeneous trapping reaction
      were sufficiently slow, then model calculations show that contaminant uptake
      could be controlled solely by reaction kinetics, although the sampling rates
      would be lower than those observed and predicted for the Cl2 case.

PMID- 7502994
TI  - Exposures while applying commercial disinfectants.
AB  - Measurements were made on 40 applicators applying chemical disinfectants to
      floors, walls, other hard surfaces, or carpeting by high-pressure spray, low
      pressure spray, mopping, wiping, or aerosol spray. Inhalation exposure was
      assessed with air samples. Clothing and skin deposition was assessed with dermal
      gauze dosimeters attached both outside applicators' work clothing and inside
      their clothing against their skin. As is typical of agricultural pesticide
      applications, the airborne route of exposure was very low, usually below the
      chemical limit of detection. The primary route of exposure and dosing was to the
      skin. The normal work clothing worn by applicators consistently reduced clothing
      deposition to lower values reaching the skin. The effects of chemical detection
      limits and short use durations caused the analyte on many individual dosimeters
      to be below the method detection limit. Mean measured total dose of the active
      ingredient onto the skin (ranging from 0.1 to 26 mg per task) was converted to
      equivalent dose of the applied mixture (ranging from 0.1 to 2.7 g) to adjust for
      widely varying disinfectant concentrations. A discussion is also presented on the
      serious limitations of applying the assumption that undetectable samples are "one
      half the detection limit" to a study of this nature where results are the sum of
      multiple measurements.

PMID- 7502995
TI  - The sensitive individual and the indoor environment: case study.
AB  - This case study describes an indoor environment investigation initiated in
      response to numerous health and comfort complaints suspected of being associated
      with a two-story office building. Conventional indoor environment investigation
      techniques were applied in an attempt to identify one or several contributing
      factors, such as inadequate outdoor air ventilation and the presence of a
      respiratory irritant. The air quality satisfaction percentage in the building was
      well above 80%; however, at least one individual was experiencing a fairly severe
      reaction only upon entering the subject building. Evaluating the building indoor
      conditions as acceptable without attempting to address all possible building
      related causes and communicating findings to interested occupants would likely
      have resulted in more occupant complaints and increased the potential for
      hysteria conditions. This investigation necessarily addressed a sensitive
      individual and involved an occupational physician as a constructive participant
      in the investigation.

PMID- 7502996
TI  - Dust mite allergens in the office environment.
AB  - The objective of this study was to evaluate the extent of dust mite infestation
      and its contribution to the health complaints in office settings. The methodology
      recommended for residential dwellings was evaluated for use in the work
      environment. Der p I allergen-specific ELISA was chosen as a primary method. A
      liquid chromatography method for guanine is suggested as a backup method to cover
      a few cases where other mite species may be encountered. The levels of dust mite
      allergens were measured in 14 offices in response to numerous health complaints.
      Approximately one-half of the offices investigated were identified as having a
      dust mite population. Four offices showed levels of Der p I in the dust greater
      than 1 microgram/g. In two offices, the dust mite allergens were the source of
      the health complaints. In the other two offices, dust mite allergens were one of
      the contaminants in the office environment. In all cases, the infestation of dust
      mites in the offices was localized to a few specific work areas. Office chairs
      were the primary location where dust mites thrived. The remedial measures
      included regular cleanup of all fabric-covered office furnishings. Steam cleaning
      was recommended to eliminate dust mite populations.

PMID- 7502997
TI  - Beyond air quality--factors that affect prevalence estimates of sick building
      syndrome.
AB  - If the prevalence of sick building syndrome (SBS) is estimated before
      intervention begins, then a reduction in the estimate may later be used to
      measure success of the intervention, and in particular, those efforts toward
      improving air quality. However, the measure of success will be distorted if
      factors other than air quality affect the SBS prevalence estimate. In this study
      the background prevalence of SBS was estimated and study factors identified that
      alone affected the estimate. Two symptom questionnaires were randomly
      administered to workers from 39 offices before routine physical examinations; one
      questionnaire described the SBS study, the other did not. SBS was defined as a
      symptom in the prior 24-hour or 7-day recall period that was more severe at work
      and not related to suspected confounders--allergy, cold, flu. Prevalence and
      prevalence ratios were estimated along with 95% confidence intervals (CI).
      Symptoms were reported by 45% of 1088 workers surveyed, but most reported them as
      more severe outside work or related them to confounders. SBS prevalence was 5%.
      It was 3.2 times higher (95% CI: 1.8, 5.7) among workers cognizant of the study
      relative to those blinded, 2.2 times higher (95% CI: 1.2, 4.1) for the 7-day
      relative to the 24-hour recall period, and 2.5 times higher (95% CI: 1.4, 5.0)
      for females. SBS prevalence did not differ by workday or age. Since study factors
      alone affected prevalence estimates, a standardized assessment method seems
      necessary for SBS.

PMID- 7502998
TI  - Pet ownership, social support, and one-year survival after acute myocardial
      infarction in the Cardiac Arrhythmia Suppression Trial (CAST).
AB  - Social support and pet ownership, a nonhuman form of social support, have both
      been associated with increased coronary artery disease survival. The independent
      effects of pet ownership, social support, disease severity, and other
      psychosocial factors on 1-year survival after acute myocardial infarction are
      examined prospectively. The Cardiac Arrhythmia Suppression Trial provided
      physiologic data on a group of post-myocardial infarction patients with
      asymptomatic ventricular arrhythmias. An ancillary study provided psychosocial
      data, including pet ownership, social support, recent life events, future life
      events, anxiety, depression, coronary prone behavior, and expression of anger.
      Subjects (n = 424) were randomly selected from patients attending participating
      Cardiac Arrhythmia Suppression Trial sites and completed baseline psychosocial
      questionnaires. One year survival data were obtained from 369 patients (87%), of
      whom 112 (30.4%) owned pets and 20 (5.4%) died. Logistic regression indicates
      that high social support (p < 0.068) and owning a pet (p = 0.085) tend to predict
      survival independent of physiologic severity and demographic and other
      psychosocial factors. Dog owners (n = 87, 1 died) are significantly less likely
      to die within 1 year than those who did not own dogs (n = 282, 19 died; p <
      0.05); amount of social support is also an independent predictor of survival (p =
      0.065). Both pet ownership and social support are significant predictors of
      survival, independent of the effects of the other psychosocial factors and
      physiologic status. These data confirm and extend previous findings relating pet
      ownership and social support to survival among patients with coronary artery
      disease.

PMID- 7502999
TI  - Plasma levels of the antioxidant selenium and risk of myocardial infarction among
      U.S. physicians.
AB  - The well-known antioxidant properties of selenium have been linked to a lower
      incidence of cardiovascular disease in humans, but the findings remain
      controversial. To explore whether the plasma selenium level predicts risk of
      myocardial infarction (MI), we analyzed prospectively collected plasma samples in
      a nested case-control study among participants in the Physicians' Health Study, a
      randomized trial of aspirin and beta-carotene. Blood specimens were collected
      between August 1982 and December 1984 and stored at -80 degrees C. All infarcts
      were documented by medical records. This study is based on 251 subjects who had
      infarctions and an equal number of healthy controls, matched by age, smoking
      status, and time from randomization. The mean +/- SD levels of plasma selenium
      were 114.4 +/- 15.1 ng/g in the cases with MI, and 113.2 +/- 15.7 ng/g in
      controls (paired t = 0.94, p = 0.35). Conditional logistic regression analysis by
      quintile of plasma selenium levels showed no suggestion of any protective effect
      of selenium; subjects in the highest quintile had a relative risk of 1.27 (95%
      confidence interval 0.71 to 2.29) when compared with the bottom quintile, and
      1.53 (95% confidence interval 0.61 to 3.84) after adjustment for other
      cardiovascular risk factors. These data provide no evidence for an association
      between increased plasma selenium and reduced risk of MI at the current levels of
      selenium intake within the U.S.

PMID- 7503000
TI  - Immediate and reversible platelet inhibition after intravenous administration of
      a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary
      intervention.
AB  - We studied the pharmacokinetic and pharmacodynamic properties of integrelin, a
      novel platelet glycoprotein IIb/IIIa receptor inhibitor, in patients undergoing
      elective percutaneous coronary intervention. Patients were randomized to placebo
      (n = 19) or to 1 of 4 integrelin dosing regimens (total n = 54) that were studied
      sequentially. All patients received aspirin and heparin. Patients were followed
      until discharge for the occurrence of adverse clinical events: death, myocardial
      infarction, coronary artery bypass surgery, repeat intervention, or recurrent
      ischemia. Bleeding was the primary safety end point. Frequent blood sampling was
      performed for adenosine diphosphate-induced platelet aggregations. Simplate
      bleeding times were performed. Adverse clinical events occurred less often in the
      integrelin-treated patients, although the overall numbers were too small to make
      a definitive statement as to clinical efficacy. There was no significant increase
      in serious bleeding among integrelin-treated patients. The 2 highest integrelin
      boluses (180 and 135 micrograms/kg) immediately (15 minutes after the bolus)
      provided > 80% inhibition of adenosine diphosphate-induced platelet aggregation
      in > 75% of treated patients. A constant integrelin infusion of 0.75
      micrograms/kg/min maintained this marked antiplatelet effect, whereas an infusion
      of 0.50 micrograms/kg/min allowed gradual recovery of platelet function. Elective
      coronary intervention was performed safely and with no significant increase in
      serious bleeding events using integrelin with aspirin and heparin as an
      antithrombotic regimen. Integrelin provided rapid, intense, and persistent ex
      vivo platelet inhibition during coronary intervention. This new antiplatelet
      agent may be beneficial in reducing platelet-mediated ischemic complications of
      percutaneous coronary intervention.

PMID- 7503001
TI  - Chronotropic response to exercise predicts angiographic severity in patients with
      suspected or stable coronary artery disease.
AB  - Inappropriate chronotropic response to exercise has been observed to correlate
      with poor prognosis in patients with coronary disease, but the mechanism for this
      association is not well defined. We attempted to examine the association between
      chronotropic response to exercise and angiographic severity of coronary disease
      in patients with suspected or stable coronary artery disease. The chronotropic
      response, expressed as peak heart rate, chronotropic index (ratio of heart rate
      reserve and metabolic reserve utilized), or percent maximal heart rate achieved,
      was correlated with angiographic findings obtained within 180 days of the test.
      Significant coronary disease was defined as > or = 1 stenosis of > or = 50% in a
      major epicardial artery or its main branches; severe coronary disease was defined
      as > or = 50% stenosis in all 3 epicardial arteries, or in the left main coronary
      trunk, or 2-vessel disease with > or = 70% proximal left anterior descending
      artery stenosis. We observed that peak heart rate and percent maximal heart rate
      achieved were independent negative predictors of both significant and severe
      coronary disease by logistic regression. The chronotropic index predicted severe
      coronary disease only. All 3 parameters of chronotropic response exhibited a
      significant gradient of abnormality across the spectrum of coronary disease (p <
      0.01 for all), expressed by the number of vessels involved and correlated with
      left anterior descending artery involvement (p < 0.05 for all). We conclude that
      chronotropic response to exercise predicts the presence and angiographic severity
      of coronary disease. This association is likely related to the proportion of left
      ventricular myocardium rendered ischemic during stress.

PMID- 7503002
TI  - Dietary intake, plasma levels of antioxidant vitamins, and oxidative stress in
      relation to coronary artery disease in elderly subjects.
AB  - The prevalence of coronary artery disease (CAD) in the urban population of India
      is similar to that in developed countries; Indian immigrants in industrialized
      countries have the highest prevalence of CAD. This is a cross-sectional survey
      within a random sample of a single urban setting in India. The relation between
      risk of CAD and plasma levels of vitamins A, C, E, and beta-carotene was examined
      in 72 of 595 elderly subjects (12.1%) with CAD (aged 50 to 84 years). Plasma
      levels of vitamins A, C, E, and beta-carotene were significantly related to risk
      of CAD. Smoking (n = 145) and diabetes (n = 70) were the confounding factors.
      Lipid peroxides were higher in patients with CAD and diabetes, and in those who
      smoked. The inverse relation between CAD and low plasma vitamin C was
      substantially reduced after adjustment for smoking and diabetes. Vitamin A and E
      levels remained independently and inversely related to the risk of CAD after
      adjustment for age, smoking, diabetes, blood pressure, blood lipoproteins, and
      relative weight and body mass index. The adjusted odds ratios for CAD between the
      lowest and highest quintiles of vitamin E levels were 2.53 (95% confidence
      interval [CI] 1.11 to 5.31), vitamin C, 2.21 (95% CI 1.12 to 3.15), and beta
      carotene, 1.72 (95% CI 0.88 to 3.62). The fatty acid composition of the diet,
      blood lipid levels, central obesity (waist-hip ratio), smoking habits, blood
      pressure, and plasma insulin levels do not appear to account for high rates of
      CAD among elderly Indians.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503003
TI  - Noninvasive tracking of coronary atherosclerosis by electron beam computed
      tomography: rationale and design of the Felodipine Atherosclerosis Prevention
      Study (FAPS).
AB  - The Felodipine Atherosclerosis Prevention Study is designed to evaluate the
      efficacy of the calcium antagonist felodipine ER and combined
      felodipine/simvastatin therapy on retarding the progression of atherosclerosis,
      estimated by serial changes in coronary calcium evaluated by noninvasive electron
      beam computed tomography. Subjects include 180 men and women aged 40 to 69 and 50
      to 69 years, respectively, with moderate type IIa dyslipidemia, with either
      cardiovascular disease or risk factors. All subjects receive simvastatin lipid
      lowering therapy, and are randomized either to felodipine or placebo for a
      treatment period of 2 years. Monitoring of blood chemistry, measures of lipids
      and apolipoproteins, blood pressure, evaluation of symptoms, and interim clinical
      event monitoring are done at routine follow-up visits. Baseline and 2-year follow
      up electron beam computed tomography, measuring changes in total calcium score,
      area, and mass, evaluate the effects of intervention on the progression of
      calcified atherosclerosis. The results from the Felodipine Atherosclerosis
      Prevention Study will provide valuable information about the effect of felodipine
      alone and in combination with simvastatin on progression of calcified
      atherosclerosis evaluated noninvasively.

PMID- 7503004
TI  - Atrial flutter termination by overdrive transesophageal pacing and the
      facilitating effect of oral propafenone.
AB  - Transesophageal overdrive atrial pacing is effective and safe for atrial flutter
      termination. The influence of antiarrhythmic drug therapy on this procedure is
      controversial. In this study, we investigated whether oral propafenone may
      facilitate this procedure. Thirty patients with type I atrial flutter were
      randomized into 2 groups in which transesophageal pacing was attempted: group A,
      without treatment; and group B, after oral administration of propafenone 600 mg.
      Transesophageal pacing was effective in interrupting atrial flutter in 53% of
      patients (8 of 15) in group A and in 87% of patients (13 of 15) in group B. A
      significant lengthening of the flutter cycle was observed with respect to the
      baseline in patients given propafenone (261 +/- 23 vs 217 +/- 25, p < 0.01).
      Sinus rhythm resumed at a shorter paced cycle in group A patients (166 +/- 13 vs
      187 +/- 14 ms, p < 0.01). The transesophageal threshold for stable atrial capture
      was significantly lower in group A (20.5 +/- 0.2 vs 23.3 +/- 1.2, p < 0.01). In
      no patient was the threshold for atrial capture higher than the pain threshold.
      We did not observe abrupt enhancement of atrioventricular conduction. We conclude
      that propafenone is effective and safe when used with transesophageal pacing in
      the termination of atrial flutter. The slowing effect of the drug on intraatrial
      conduction and the possible stabilizing effect on the reentry circuit appear to
      be outweighed by the positive effect of propafenone on the excitable gap of the
      circuit, facilitating its capture and accounting for the beneficial effect of the
      drug on arrhythmia termination.

PMID- 7503005
TI  - Evaluation of end points of serial drug testing in patients with sustained
      ventricular tachycardia after healing of acute myocardial infarction.
AB  - Serial electrophysiologic drug testing was used to guide antiarrhythmic therapy
      in a consecutive series of 150 patients with clinical sustained ventricular
      tachycardia (VT) or cardiac arrest and inducible monomorphic VT. All patients had
      coronary artery disease and a history of myocardial infarction. For patients with
      clinical sustained VT, drug responders and partial drug responders (VT slowed by
      drug to rate < 150 beats/min, with systolic blood pressure > or = 90 mm Hg) had
      similar total mortality rates (2-year actuarial survival 100% and 94%, p = NS),
      which were statistically different from that of patients with drug inefficacy (2
      year survival 67%). Partial drug responders had high arrhythmia recurrence rates,
      similar to those of patients with drug inefficacy. For cardiac arrest survivors,
      the results of electrophysiologically guided drug testing did not predict
      prognosis. Patients with a change in mode of VT induction during antiarrhythmic
      therapy had a favorable prognosis (no deaths during follow-up).

PMID- 7503006
TI  - Comparison of effects on peak oxygen consumption, quality of life, and
      neurohormones of felodipine and enalapril in patients with congestive heart
      failure.
AB  - Angiotensin-converting enzyme (ACE) inhibition is currently the cornerstone of
      congestive heart failure (CHF) therapy, but these drugs are not tolerated in up
      to 20% of patients. For these patients, therapeutic alternatives with comparable
      efficacy are needed. Felodipine, a vasoselective dihydropyridine calcium
      antagonist with a slow onset of action and a long plasma half-life, may be such
      an agent. Therefore, the efficacy and safety of felodipine were examined and
      compared with enalapril using a double-blind design. We studied 46 patients with
      a left ventricular ejection fraction < 0.40, peak oxygen consumption < 20 ml.min
      1.kg-1, and symptoms of CHF despite therapy with diuretics and digoxin. After 16
      weeks of therapy, there were no statistically significant differences in peak
      oxygen consumption (felodipine +1.6, enalapril +2.5 ml.min-1.kg-1) and exercise
      tolerance (felodipine +61 seconds, enalapril +64 seconds). Quality-of-life
      parameters were affected slightly better by felodipine than by enalapril. Plasma
      norepinephrine decreased by 143 pg.ml-1 with enalapril and by 12 pg.ml-1 with
      felodipine (p < 0.20 between groups). Both drugs were generally well tolerated.
      These data suggest that felodipine and enalapril have comparable effects on
      exercise parameters in patients with CHF. Neurohumoral activation was not
      observed with either drug.

PMID- 7503007
TI  - Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in
      chronic congestive heart failure secondary to coronary artery disease.
AB  - In chronic heart failure, a diuretic plus an angiotensin-converting enzyme (ACE)
      inhibitor only partially suppresses aldosterone despite the fact that aldosterone
      has many harmful effects independent of angiotensin II. These possible harmful
      effects of aldosterone are magnesium loss, increased cardiac sympathetic
      activity, and increased ventricular arrhythmias. We have therefore assessed
      whether adding the aldosterone antagonist, spironolactone, to a loop diuretic and
      ACE inhibitor reverses any of these potentially harmful effects of residual
      aldosterone. In a preliminary animal study, we found that exogenous aldosterone
      reduced myocardial norepinephrine uptake by 24% in anesthetized rats in vivo. In
      our main study, 42 patients with New York Heart Association II to III congestive
      heart failure were randomized to spironolactone (50 to 100 mg/day, titrated to
      blood pressure and plasma potassium) or placebo in a double-blind fashion. Our
      principal finding is that cardiac norepinephrine uptake as assessed by 123I
      metaiodobenzylguanidine scintigraphy increased with spironolactone (p < 0.01).
      Spironolactone also elevated plasma magnesium (p < 0.05), reduced urinary
      magnesium excretion (p < 0.05), and caused a reduction in ventricular arrhythmias
      on 24-hour ambulatory electrocardiography (p < 0.05). Spironolactone increased
      plasma renin activity, plasma aldosterone (p < 0.01), 24-hour urinary sodium
      excretion (p < 0.05), and urinary sodium/potassium ratio (p < 0.01).
      Echocardiographic-determined measurements of left ventricular systolic and
      diastolic function were unaltered by spironolactone.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7503008
TI  - Results of percutaneous double-balloon mitral commissurotomy in one medical
      center in Tunisia.
AB  - Percutaneous balloon mitral commissurotomy was attempted in Tunisia, where
      rheumatic fever is still endemic, in 463 consecutive patients with severe
      rheumatic mitral valve stenosis. Their mean age +/- SD was 33 +/- 12 years (range
      8 to 68), 324 patients (70%) were women, and 327 (71%) were in sinus rhythm.
      Valvotomy was technically successful in 454 patients (98%). The mean mitral valve
      gradient decreased from 20 +/- 7 to 6 +/- 4 mm Hg, mean left atrial pressure
      decreased from 27 +/- 8 to 15 +/- 6 mm Hg, cardiac index increased from 3.0 +/-
      0.7 to 3.6 +/- 0.8 L/min/m2, and Gorlin mitral valve area, from 0.97 +/- 0.19 to
      2.2 +/- 0.4 cm2 (all p < 0.001). Two-dimensional echocardiographic mitral valve
      area increased from 1.03 +/- 0.18 to 2.15 +/- 0.36 cm2 (p < 0.00001). A final
      valve area of > or = 1.5 cm2 was achieved in 98% of patients. Multivariate
      analysis identified a pre-mitral valve area < 0.8 cm2 and an echocardiographic
      score (echo score) > or = 12 as the strongest predictors of residual stenosis
      (final mitral valve area < 1.5 cm2). Major procedural complications included
      mortality (0.4%), tamponade (0.7%), thromboembolism (2.0%), severe mitral
      regurgitation (4.6%), significant (pulmonary to systemic flow ratio > or = 1.5)
      interatrial shunt (4.8%). Four hundred thirty patients were followed up between 6
      and 82 months (mean 37 +/- 22): 95% were in functional class I to II without
      reintervention, and 7 patients died (1.6%); restenosis (echocardiographic mitral
      valve area < 1.5 cm2) occurred in 10.4% of patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7503009
TI  - Role of beta-adrenergic receptor downregulation in the peak exercise response in
      patients with heart failure due to idiopathic dilated cardiomyopathy.
AB  - The effect of beta-adrenergic receptor downregulation on peak exercise response
      in patients with heart failure has not been directly investigated. Seventy-two
      patients with idiopathic dilated cardiomyopathy who had a mean ejection fraction
      of 23 +/- 1% (mean +/- SEM) and New York Heart Association class II or III
      symptoms were investigated. Subjects underwent maximal exercise testing on a
      bicycle or a treadmill, hemodynamic assessment by right heart catheterization,
      and measurement of total beta-adrenergic receptor density by 125I
      iodocyanopindolol binding performed in the right ventricular endomyocardial
      biopsy tissue and in peripheral lymphocytes. Endomyocardial biopsy beta
      adrenergic receptor density (Bmax) was markedly decreased (45 +/- 2 fmol/mg), and
      significantly lower than lymphocytes Bmax (107 +/- 14 fmol/mg; p < 0.05). By
      univariate analysis, all exercise variables correlated significantly with biopsy
      tissue Bmax but not with lymphocyte Bmax. Maximal exercise oxygen consumption
      (VO2max) yielded the highest correlation with Bmax (r2 = 0.61, p < 0.001). By
      stepwise regression analysis, VO2 max, delta heart rate x systolic blood
      pressure, and ejection fraction were all independently related to Bmax.
      Myocardial beta-adrenergic receptor downregulation is likely to be partially
      responsible for the reduced chronotropic and inotropic responses to peak exercise
      in patients with mild to moderate symptomatic heart failure due to idiopathic
      dilated cardiomyopathy.

PMID- 7503010
TI  - Pathologic elucidation of the echocardiographic features of Ebstein's
      malformation of the morphologically tricuspid valve in discordant
      atrioventricular connections.
AB  - We defined the morphology of the left atrioventricular valve in Ebstein's
      malformation associated with congenitally corrected transposition to elucidate
      the approach to diagnosis by echocardiography. We found 14 unequivocal cases out
      of a total of 3,720 specimens. We noted the atrial arrangement, displacement, and
      nature of the tricuspid leaflets, and axis of the plane of the tricuspid orifice.
      We constructed ratios of volume of the atrialized to the functional right
      ventricle, and of the right to left ventricle, as well as distances of the septal
      attachments of the atrioventricular junctions to the respective ventricular
      apices. Three specimens had abnormalities of cardiac position, and 8 had
      ventricular septal defect. The tricuspid valve plane was rotated 47 +/- 21
      degrees from its usual position into the ventricle. The tricuspid valvar tissue
      was variably attached to the underlying myocardium, with the most severely
      affected lesion being the mural leaflet followed by the septal leaflet, and the
      anterior leaflet attachment the least affected. Abnormalities of the tendinous
      cords and the effective valvar orifice occurred in 3 specimens. The ratio of the
      atrialized to the functional right ventricular volume was 0.74 +/- 0.49; the
      ratio of the fetal right to left ventricular volume was 1.18:1 +/- 0.70:1. These
      data suggest that plastic repairs of the right ventricle would leave a small
      functional right ventricle, but that valve replacement could restore the volume
      of the ventricle. Thus, the plane of displacement of the valve in corrected
      transposition appears less amenable to 4-chamber echocardiography than other
      forms of Ebstein's malformation. Changes in the echocardiographic planes should
      display the morphology and also provide some hemodynamic information.

PMID- 7503012
TI  - Evolution of the chronotropic response to exercise after cardiac transplantation.
AB  - The chronotropic response to exercise is abnormal in cardiac transplant
      recipients as a result of autonomic denervation. Differences in the response
      between recent transplant recipients and longer-term survivors have been
      described in previous cross-sectional studies. These changes have not been
      assessed directly using serial studies. The effect of sinus node dysfunction on
      the chronotropic response has not previously been determined. Thirty-one
      transplant recipients underwent serial treadmill exercise tests using the
      chronotropic exercise assessment protocol 3 and 6 weeks and 3 and 6 months after
      transplantation. Sinus node function was assessed using standard
      electrophysiologic techniques. The chronotropic response increased between 3 and
      6 weeks after transplantation in all subjects. Six months after transplantation,
      there was a further marked increase in the response in a subgroup of 5 subjects.
      These subjects also had a dramatic decrease in heart rate on cessation of
      exercise. Three subjects had abnormal sinus node function. Although heart rates
      and chronotropic response were below average in these subjects, 2 other subjects
      with normal sinus node function on electrophysiologic testing had lower heart
      rates and worse chronotropic responses. Thus, the chronotropic response to
      exercise evolves over the first 6 weeks after cardiac transplantation in all
      subjects. In a number of recipients (16%), there is a marked increase in
      chronotropic response between 3 and 6 months, which suggests efferent sympathetic
      reinnervation. There was no clear difference in chronotropic response between
      subjects with and without evidence of sinus node dysfunction.

PMID- 7503011
TI  - Echocardiographic evaluation of congenital mitral valve anomalies in children.
AB  - Congenital mitral valve anomalies were diagnosed in 65 children, whose ages
      ranged from newborn to 18 years, using 2-dimensional, color, pulsed-, and
      continuous-wave Doppler ultrasound. Data were collected over 7.5 years from
      13,400 new studies. Data in these patients were compared with those obtained by
      cardiac catheterization, cardiac surgery, and autopsy. We detected 4 different
      lesions: (1) congenital mitral stenosis with 2 papillary muscles (n = 24); (2)
      parachute mitral valve, with a single papillary muscle (n = 24); (3) isolated
      cleft in the mitral valve (n = 10); and (4) double-orifice mitral valve (n = 7).
      A supravalvar mitral ring was detected in 21 patients with mitral stenosis;
      however, it never occurred as an isolated lesion and was invariably associated
      with some other left ventricular inflow or outflow obstruction. The supravalvar
      ring was associated with a parachute deformity of the mitral valve in 17
      patients; in only 4 was this abnormality associated with mitral stenosis with 2
      papillary muscles. In patients with congenital mitral stenosis, the peak and mean
      transmitral Doppler velocities were increased significantly compared with those
      in controls (peak velocity 1.53 +/- 0.74 vs 0.86 +/- 0.25 m/s, respectively, p <
      0.01; mean velocity 1.13 +/- 0.61 vs 0.58 +/- 0.11 m/s, respectively, p < 0.01).
      The correlation between mean transmitral pressure gradient obtained by Doppler
      and cardiac catheterization was fair (r = 0.75). However, the correlation between
      the mitral valve areas calculated by the Doppler pressure half-time method and by
      the Gorlin formula was poor (r = 0.57).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503013
TI  - Significance of precordial T-wave increase during treadmill stress testing.
AB  - It appears that a T-wave amplitude increase of > or = 2.5 mm in lead V2 during a
      treadmill stress test may be specific (95%), even though this finding only occurs
      occasionally. Therefore, a T-wave amplitude increase during an exercise test may
      aid in the diagnosis of the few patients who develop this abnormality, especially
      if there is no ST depression, as has occurred during several recent exercise
      tests.

PMID- 7503014
TI  - Ventricular late potentials and left ventricular function after early enalapril
      treatment in acute myocardial infarction.

PMID- 7503015
TI  - Evidence of compensatory preload adjustment on early filling phase in patients
      with stable angina pectoris and good left ventricular systolic function.

PMID- 7503016
TI  - Diagnosis of intermittent obstruction of mechanical mitral valve prostheses by
      Doppler echocardiography.
AB  - In summary, this is a report on 5 various malfunctioning mechanical monocuspid
      mitral prostheses in which Doppler demonstrated intermittent restriction to the
      prosthetic disc opening, resulting in intermittent obstruction. In all 5
      patients, it was mainly this abnormal Doppler signal that alerted us to the
      presence of prosthetic valve malfunction. In the 3 asymptomatic patients, the
      variable and intermittent increased delay in prosthetic valve opening was shown
      to be an early and sensitive echocardiographic sign of prosthesis malfunction in
      the absence of any significant increase in pressure gradients.

PMID- 7503017
TI  - Prevalence of myxomatous mitral valve prolapse in patients with lymphocytic
      thyroiditis.
AB  - In conclusion, given the cardiac (mitral regurgitation, endocarditis,
      thromboembolic complications, arrhythmic sudden death) and neurologic (cerebral
      embolic event) complications of the pathologic forms of MVP, physicians should
      look carefully for myxomatous involvement of the mitral valve and prolapse in
      patients with autoimmune thyroid diseases. Patients should be monitored and
      prophylactic antibiotic treatment recommended when appropriate.

PMID- 7503018
TI  - Guidance of radiofrequency catheter ablation by transesophageal echocardiography
      in children with palliated single ventricle.

PMID- 7503019
TI  - Determination of ventricular volumes in human fetal hearts by two-dimensional
      echocardiography.
AB  - In conclusion, ventricular volume calculation from 2DE is feasible in the human
      fetus and improves the ability to calculate fetal ventricular size and ejection
      fraction. The right ventricle is clearly dominant at midgestation, but approaches
      left ventricular size at term. Calculation of the ventricular output from 2DE
      volume measurements is an accurate alternative to Doppler measurements.

PMID- 7503020
TI  - Treatment of a "lost" unexpanded intracoronary stent in a patient with unstable
      angina.

PMID- 7503021
TI  - Day-to-day cardiology in Bombay, India.

PMID- 7503022
TI  - Single-stage coronary angiography and angioplasty: a new standard.

PMID- 7503023
TI  - Sexual activity and coronary artery disease: multiple options.

PMID- 7503024
TI  - I view with panic.

PMID- 7503025
TI  - Coronary sinus pacing mistaken as interventricular septal perforation and
      subsequent left ventricular pacing by a transvenously introduced pacing
      electrode.

PMID- 7503026
TI  - QT dispersion: proposed technique for optimal risk stratification.

PMID- 7503027
TI  - Suggested change to the transfer case protocol.

PMID- 7503029
TI  - Comments on Dr. Rinchuse's Counterpoint discussion.

PMID- 7503028
TI  - The importance of the occlusal plane.

PMID- 7503030
TI  - Comments on Dr. Rinchuse's Counterpoint discussion.

PMID- 7503031
TI  - More comments on Rinchuse Counterpoint.

PMID- 7503032
TI  - More comments on Rinchuse Counterpoint.

PMID- 7503033
TI  - A "patient" patient: 22 years in bands.

PMID- 7503034
TI  - Ceramic bracket design: an analysis using the finite element method.
AB  - This investigation was designed to generate finite element models for selected
      ceramic brackets and graphically display the stress distribution in the brackets
      when subjected to arch wire torsion and tipping forces. Six commercially
      available ceramic brackets, one monocrystalline and five polycrystalline alumina,
      of twin bracket design for the permanent maxillary left central incisor were
      studied. Three-dimensional computer models of the brackets were constructed and
      loading forces, similar to those applied by a full-size (0.0215 x 0.028 inch)
      stainless steel arch wire in torsion and tipping necessary to fracture ceramic
      brackets, were applied to the models. Stress levels were recorded at relevant
      points common among the various brackets. High stress levels were observed at
      areas of abrupt change in geometry and shape. The design of the wire slot and
      wings for the Contour bracket (Class One Orthodontic Products, Lubbock, Texas)
      and of the outer edges of the wire slot for the Allure bracket (GAC, Central
      Islip, N.Y.) were found to be good in terms of even stress distribution. The
      brackets with an isthmus connecting the wings seemed to resist stresses better
      than the one bracket that did not have this feature. The design of the isthmus
      for the Transcend (Unitek/3M, Monrovia, Calif.) and Lumina (Ormco, Glendora,
      Calif.) brackets were found to be acceptable as well. The Starfire bracket ("A"
      Company, San Diego, Calif.) showed high stresses and irregular stress
      distribution, because it had sharp angles, no rounded corners, and no isthmus.
      The finite element method proved to be a useful tool in the stress analysis of
      ceramic orthodontic brackets subjected to various forces.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7503035
TI  - Clinical results of the maxillary protraction in Korean children.
AB  - Sixty subjects with ages ranging from 8 to 13 years were divided into two groups
      according to the intraoral appliances used. Group I consisted of 47 subjects with
      rapid palatal expansion (RPE) appliances and group II consisted of 13 subjects
      with labiolingual appliances (La/Li). Group I was subdivided into three subgroups
      by age and two subgroups by the timing of the protraction. The cephalometric
      radiographs of all subjects were analyzed before and after correction of anterior
      crossbite. The following results were obtained: (1) After maxillary protraction,
      the maxilla and maxillary dentitions moved forward and downward, and the mandible
      and mandibular dentitions moved backward and downward. (2) The maxilla moved more
      forward in the RPE group, compared with La/Li group. (3) The palatal plane angle
      decreased more in the protraction-during-palatal-expansion group than protraction
      after-palatal-expansion group. (4) Age did not show any statistically significant
      difference.

PMID- 7503036
TI  - Gingival invagination area after space closure: a histologic study.
AB  - The aim of this study was to show the micromorphologic findings (epithelium,
      connective tissue, bone) in a region of pronounced gingival invagination after
      space closure by analyzing a maxilla taken in autopsy from a 19-year-old woman
      who was orthodontically treated. The dental records were also at our disposal.
      The second left premolar was congenitally absent. This area displayed before
      therapeutic horizontal bone atrophy. For space closure, the first upper left
      molar was moved mesially with a fixed appliance. After space closure, pronounced
      gingival invagination was diagnosed. The lateral segments of the specimen were
      prepared histologically in the horizontal plane. The microscopic observations
      revealed deep epithelial proliferation, hyperkeratinization, and one isolated
      keratin pearl in the connective tissue. Irrespective of location, the broad
      connective tissue layer showed disparate characteristics. Cell-rich, loose
      connective tissue with low fiber density were dominant in the subepithelial
      layer. The epiperiosteal layer displayed multiple tough fibers, some running
      parallel, some with reticular meshing, permeated with many blood vessels. Very
      few inflammatory cells were detected in the soft tissue. The bone had been
      resorbed in the mesiopalatal area of the molar (tooth movement direction) apart
      from one small isolated bony islet. These observations suggest that inflammatory
      influences were unlikely for marginal bone loss mesiopalatal to the tooth.

PMID- 7503037
TI  - Simulation of condylar growth in the cat with pulsating electromagnetic currents.
AB  - Orthodontists have been, and are, interested in influencing facial growth,
      specifically, mandibular growth. The purpose of this investigation is to enhance
      condylar growth by means of electric stimulation. Eight growing cats were
      bilaterally condylotomized and unilaterally at random received electric
      stimulation. Before the condylotomy bonemarkers were implanted in the zygomatic
      process and above the condylotomy site. The condylotomy effectively separated the
      head of the condyle from the body of the mandible, thus unloading the head. After
      5 weeks, implant separation indicated increased condylar growth on the treated
      side of all eight cats. Histologically, the treated condyles of six cats were
      different from the controls in that the hypertrophic zone was irregular and
      vascularization increased. The treated condyle showed significantly more
      bonemarker separation than the control condyle. On average, the treated condyle
      showed 1.24 mm more separation than the control (p = 0.001 by the paired sample t
      test).

PMID- 7503038
TI  - Changes in tooth size-arch length relationships from the deciduous to the
      permanent dentition: a longitudinal study.
AB  - The purpose of this investigation is to determine the changes in the maxillary
      and mandibular tooth size-arch length relationship (TSALD) after the complete
      eruption of the deciduous dentition (mean age = 4.0 years) to the time of
      eruption of the second molars (mean age = 13.3 years). In addition, an attempt
      was made to determine whether TSALD in the permanent dentition can be predicted
      in the deciduous dentition. Records on 35 male and 27 female subjects were
      evaluated. Each subject had a clinically acceptable occlusion--that is, a normal
      molar and canine relationship, at the time of eruption of the deciduous and
      permanent teeth. In addition, each subject had a complete set of data at the two
      stages of dental development. These selection criteria limited the number of
      subjects in this investigation to 62. The mesiodistal diameter of all deciduous
      teeth and their permanent successors, as well as various dental arch width and
      length parameters, were measured in the deciduous and permanent dentitions. A
      total of 68 parameters were measured or calculated. Student t tests were used to
      determine whether significant differences were present between the right and left
      sides for both male and female subjects. Correlation coefficients r were
      performed between the deciduous and the corresponding permanent teeth and also
      for the arch length parameters, as well as TSALD in the two dentitions.
      Significance was predetermined at the 0.05 level of confidence. Stepwise
      regression analysis (R2) was used to determine which of the variables in the
      deciduous dentition could be included in a regression model to determine
      associations between maxillary and mandibular TSALD in the permanent
      dentition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503039
TI  - A clinical investigation of the efficacy of low level laser therapy in reducing
      orthodontic postadjustment pain.
AB  - Low level laser therapy (LLLT) has been shown to produce analgesic effects in
      many clinical applications. The aim of this clinical study was to test the
      efficacy of LLLT in controlling orthodontic postadjustment pain. Thirty-nine
      volunteers were selected for this study that used a double-blind design with
      placebo control. Elastomeric separators were placed at the proximal contacts of
      one premolar in each quadrant of the dentition to induce orthodontic pain. The
      tip of a 30 mW gallium-arsenide-aluminium (830 nm) diode laser probe was then
      placed at the buccal gingiva and directed at the middle third of the root. Three
      different treatment durations of 15, 30, and 60 seconds and one placebo treatment
      of 30 seconds were tested within each subject. The study was conducted over 5
      days, and the visual analogue scale (VAS) was used to quantify the pain
      experienced by the subjects before and after laser applications for each day.
      Analysis of the VAS median scores showed that teeth exposed to laser treatment
      had lower levels of pain as compared with those with the placebo treatment.
      However, nonparametric statistical analysis of the data showed that the
      differences between treatments and placebo within each subject were not
      statistically significant.

PMID- 7503040
TI  - Pulpal response in electrothermal debonding.
AB  - An alternative method to conventional bracket removal that minimizes the
      potential for ceramic bracket failure as well as trauma to the enamel surface is
      electrothermal debonding (ETD). However, the potential for pulpal damage using
      ETD on ceramic brackets still needs assessment. The purpose of this research is
      to investigate and assess any pulpal damage caused by ETD. Ten patients requiring
      four premolar extractions each were randomly selected (5 boys and 5 girls).
      Ceramic brackets were bonded to experimental and control teeth. A total of 30
      teeth were used to provide histologic material of the human pulp. Fifteen teeth
      were extracted 24 hours after ETD, seven were extracted 28 to 32 days after ETD,
      and eight were the control teeth and debonded by a conventional method, with
      pliers. The pulp was normal in most cases in the control group. There was
      significant hyperemia seen 24 hours after debonding in teeth debonded by ETD.
      Teeth extracted 30 days afer ETD showed varied responses, ranging from complete
      recovery in some cases to persistence of inflammation and pulpal fibrosis. Teeth
      subjected to the conventional debonding were normal histologically. The teeth in
      our research were healthy teeth with a rich blood supply and were from a younger
      age group. Patients with compromised teeth that have large restorations or a
      questionable pulpal status could behave more adversely to this significant amount
      of heat applied. In compromised cases and on older patients, performing pulp
      vitality tests before ETD may inform the operator about the status of the pulp
      and thereby prevent the potential for pulpal damage.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7503041
TI  - Pulp and periodontal healing, root development and root resorption subsequent to
      transplantation and orthodontic rotation: a long-term study of autotransplanted
      premolars.
AB  - One hundred and eighteen premolars transplanted at a stage with 3/4 to 4/4 root
      development with a wide open apical foramen were followed with standardized
      clinical and radiographic techniques for signs of pulpal and periodontal ligament
      healing and root development. Pulp healing, evaluated first by radiographic
      presence of pulp canal obliteration, appeared to be an earlier sign of pulp
      healing than the detection of pulp vitality with an electrometric test. Continued
      root growth of premolars was seen in some cases. Complete arrest of root
      development was usually followed by development of the missing root structure at
      the donor site, indicating a separation of the Hertwig's epithelial root sheath.
      Orthodontic rotation performed on 11 premolars induced slight surface resorption
      and a significant shortening of tooth length (mean 1.2 mm), compared with
      nontreated but transplanted control teeth. However, the extent of the apical root
      resorption is of minor clinical importance, and is equivalent to what has been
      found in previous investigations of orthodontic treatment of nontransplanted
      premolars. Late pulp necrosis occurred in 2 of the 11 treated cases 6 years after
      transplantation and 5 years after orthodontic rotation. To prevent late pulp
      necrosis, orthodontic rotation is recommended after periodontal healing and
      before total pulp canal obliteration has taken place, i.e., 3 to 9 months after
      transplantation.

PMID- 7503042
TI  - The correction of interarch malocclusions using a fixed force module.
AB  - This article describes the use of a flexible force module (the Jasper Jumper)
      that can be incorporated into existing fixed appliances to correct various types
      of sagittal malocclusion. Essentially the spring mechanism described in this
      article is a modification of the original bite jumping mechanism of Herbst. The
      flexible spring module provides greater freedom of mandibular movement than is
      possible with the more rigid mechanism of the Herbst appliance. The facial
      musculature applies force through these modules to the anchor points to produce a
      variety of treatment effects. The treatment effects produced by the module mimic
      those previously described for the Herbst appliance and include posterior
      movement of the maxillary buccal segments and anterior movement of the mandible
      or mandibular dentition or both. Specifics of the clinical management of this
      modular system are discussed, including anchorage preparation and torque
      application, as well as the methods of anchoring, activating and reactivating the
      modules.

PMID- 7503043
TI  - Nonsurgical treatment of open bite in nongrowing patients.
AB  - Successful treatment of the adult patient with an open bite dental or skeletal
      pattern often presents a difficult challenge. While the causes of open bite may
      be multifactorial in nature, there are specific diagnostic criteria that may
      allow for an orthodontic treatment modality incorporating extraction therapy with
      retraction of incisors. Two case presentations illustrate treatment of adult
      patients with open bites due to proclined incisors. The diagnostic criteria and
      mechanics for appropriate and successful treatment are discussed. Although the
      selection of extraction therapy for correction of anterior open bite has a narrow
      range of application in the overall scheme of open bite treatment, this treatment
      method has certain areas of application in which success may be anticipated.

PMID- 7503044
TI  - A special kind of computerized reporting system.

PMID- 7503045
TI  - A critical look at methods for handling missing covariates in epidemiologic
      regression analyses.
AB  - Epidemiologic studies often encounter missing covariate values. While simple
      methods such as stratification on missing-data status, conditional-mean
      imputation, and complete-subject analysis are commonly employed for handling this
      problem, several studies have shown that these methods can be biased under
      reasonable circumstances. The authors review these results in the context of
      logistic regression and present simulation experiments showing the limitations of
      the methods. The method based on missing-data indicators can exhibit severe bias
      even when the data are missing completely at random, and regression (conditional
      mean) imputation can be inordinately sensitive to model misspecification. Even
      complete-subject analysis can outperform these methods. More sophisticated
      methods, such as maximum likelihood, multiple imputation, and weighted estimating
      equations, have been given extensive attention in the statistics literature.
      While these methods are superior to simple methods, they are not commonly used in
      epidemiology, no doubt due to their complexity and the lack of packaged software
      to apply these methods. The authors contrast the results of multiple imputation
      to simple methods in the analysis of a case-control study of endometrial cancer,
      and they find a meaningful difference in results for age at menarche. In general,
      the authors recommend that epidemiologists avoid using the missing-indicator
      method and use more sophisticated methods whenever a large proportion of data are
      missing.

PMID- 7503046
TI  - Are ethical topics in epidemiology included in the graduate epidemiology
      curricula?
AB  - The objective of this study was to evaluate, via a mail questionnaire, the extent
      to which topics in epidemiology are included in the graduate epidemiology
      curricula in departments of epidemiology within the 24 US schools of public
      health. Responses from 101 faculty (79% of faculty queried) indicated that 86%
      believed that education concerning ethical issues in epidemiologic research
      should be included in the curriculum. Topics included most frequently are ethical
      issues concerning protection of human subjects, clinical trials, screening
      programs, and use/abuse of data. The most common mode of presenting these topics
      is through one-on-one mentoring or through seminars.

PMID- 7503047
TI  - Dietary vitamin C and beta-carotene and risk of death in middle-aged men. The
      Western Electric Study.
AB  - In the Western Electric Company Study, carried out in Chicago, Illinois, data on
      diet and other factors were obtained in 1958 and 1959 for a cohort of 1,556
      employed, middle-aged men. Nutrients included vitamin C and beta-carotene. An
      index that summarized combined intake of both nutrients was constructed. Mean
      intakes of vitamin C in the lowest and highest tertiles of the index were 66 and
      138 mg/day; corresponding values for beta-carotene were 2.3 and 5.3 mg/day. A
      total of 522 of 1,556 men died during 32,935 person-years of follow-up, 231 from
      coronary heart disease and 155 from cancer. After adjustment for potentially
      confounding factors, relative risks (95% confidence intervals) associated with an
      increment of 19 points in the index (difference between means of the lowest and
      highest tertiles) were 0.60 (0.39-0.93) for cancer mortality, 0.70 (0.49-0.98)
      for coronary disease mortality, and 0.69 (0.55-0.87) for all-cause mortality.
      These results support the hypothesis that consumption of foods rich in vitamin C
      and beta-carotene reduces risk of death in middle-aged men.

PMID- 7503048
TI  - Influence of systolic and diastolic blood pressure on stroke risk: a prospective
      observational study.
AB  - The purpose of this study was to estimate the influence of systolic (SBP) and
      diastolic blood pressure (DBP) on stroke risk. The Copenhagen City Heart Study is
      a prospective survey of 19,698 women and men who were invited to two
      cardiovascular examinations at 5-year intervals. Blood pressure was measured in
      participants once at each examination, together with other variables. Initial
      cases of stroke and transient ischemic attack were recorded from hospital records
      and death certificates from 1976 through 1988. When entered separately in the Cox
      regression model, both SBP and DBP had significant effects on stroke risk. In the
      lower 60% of the blood pressure distribution in the population, the relative risk
      of stroke was nearly constant, followed by a gradual increase in the upper 40% of
      blood pressure distribution. However, when SBP and DBP were entered
      simultaneously in the model, the effect of DBP vanished, while the pattern of the
      association between SBP and stroke risk remained unchanged. Persons on
      antihypertensive treatment had higher risk for stroke than non-treated persons
      with the same blood pressure, relative risk = 1.6 (95% confidence interval (CI)
      1.2-2.2). The relative risk for the highest SBP levels, shared by nearly 3% of
      the population, was 4.0 (95% CI 2.2-7.3). The attributable risk of SBP in the
      upper 40% of SBP distribution, i.e., above the mean for each age and sex group,
      was 22%. Our results indicate that: 1) the association between blood pressure and
      stroke risk was not log-linear, and 2) SBP was a stronger stroke predictor than
      DBP.

PMID- 7503049
TI  - Aneurysms of the abdominal aorta in older adults. The Rotterdam Study.
AB  - To assess the age- and sex-specific prevalence and risk factors for aneurysms of
      the abdominal aorta, the authors performed a population-based study in 5,419
      subjects (42% men, 58% women) aged 55 years and over. The proximal and distal
      diameter of the abdominal aorta were measured by ultrasound. An aneurysm was
      defined as a distal aortic diameter of 35 mm or more or a dilatation of the
      distal part of the the abdominal aorta of 50% or more. The mean distal and
      proximal aortic diameter increased 0.7 mm and 0.3 mm, respectively, with every 10
      years of age. In 2.1% (95% confidence interval (CI) 1.7-2.5) of the study
      population, an aneurysm was present, or in 4.1% (95% CI 3.2-4.9) of the men and
      0.7% (95% CI 0.4-1.0) of the women. Subjects with an abdominal aneurysm were more
      likely to be smokers and they had higher serum cholesterol levels and higher
      prevalence of cardiovascular disease compared with subjects without an aneurysm.
      The authors conclude that the ultrasound diameter of the abdominal aorta clearly
      increases with age in both men and women and that the prevalence of aneurysms of
      the abdominal aorta in older adults in relatively high, especially in men.

PMID- 7503050
TI  - Risk of dementia in patients with Parkinson's disease, epilepsy, and severe head
      trauma: a register-based follow-up study.
AB  - The authors investigated the risk of developing dementia for persons aged 50-75
      years who suffered from Parkinson's disease, epilepsy, or severe head trauma.
      They compared the risk in this patient group with the risk in a reference group
      in a follow-up study based on the linked databases of three Dutch nationwide
      morbidity registers over the years 1980-1989. The overall relative risk of
      developing dementia within 8 years in patients with Parkinson's disease who were
      initially free of dementia was 3.0 (95% confidence interval (CI) 2.9-3.1). Risk
      was especially increased in younger Parkinson's disease patients (relative risk
      (RR) = 13.2, 95% CI 6.2-28.6). For patients with epilepsy, the overall relative
      risk was 1.5 (95% CI 1.4-1.7). Severe head trauma was not associated with an
      increased risk of dementia (RR = 1.0, 95% CI 0.9-1.1). These findings suggest
      that Parkinson's disease is an important risk factor for dementia, with a
      particularly high risk in young patients with Parkinson's disease. Patients with
      epilepsy may bear a moderately increased risk of developing dementia. This study
      does not support earlier findings in retrospective case-control studies of an
      increased risk of dementia in head trauma patients.

PMID- 7503051
TI  - Relation of weight variability and intentionality of weight loss to disease
      history and health-related variables in a population-based sample of women aged
      55-69 years.
AB  - The authors examined the relation of recalled weight variability and history of
      intentional and unintentional weight loss with disease history in 41,837 older
      women. Lifetime history of disease, current medication use, health-related
      behaviors, body weight, and intentional and unintentional weight loss episodes of
      at least 20 lbs (9.1 kg) were assessed by means of two surveys, completed 6 years
      apart. Weight variability, as measured by the root mean square error around the
      linear regression line of weight on age at ages 18, 30, and 40 years, was
      positively related to disease history. Women who reported losing > or = 20 lbs (>
      or = 9.1 kg) unintentionally between the ages 18 and 39 years were more likely to
      report a history of disease than were women who had never lost > or = 20 lbs (>
      or = 9.1 kg) during this age period. Intentional weight loss episodes of > or =
      20 lbs (> or = 9.1 kg) between ages 18 and 39 years were also associated with
      higher cumulative disease prevalence. These results suggest that both
      unintentional and, to a lesser degree, intentional weight loss may contribute to
      the observed positive relation between weight loss or variability and disease.
      Prospective studies are needed to confirm whether weight variability is a risk
      factor for disease only when unintentional, or whether intentional weight loss
      also increases risk.

PMID- 7503052
TI  - Measurement of exposure to environmental tobacco smoke in pregnant women.
AB  - The authors compared three methods used to measure exposure to environmental
      tobacco smoke in pregnant women: personal air monitor, urine cotinine, and
      questionnaire. Environmental tobacco smoke exposure assessment methods were
      compared for agreement using Cohen's Kappa and the Spearman rank order
      correlation coefficient. Women who reported exposure had significantly higher
      levels of air nicotine concentration compared with women who reported no
      exposure, but urine cotinine did not differ. Air nicotine was more highly
      correlated with home exposure (r = 0.34) than work exposure (r = 0.18). Urine
      cotinine correlated with work exposure (r = 0.14) but neither home nor social
      exposure. Agreement was "fair" (Kappa = 0.29) when self-reported exposure was
      compared with air monitor, but agreement was "poor" when urine cotinine was
      compared with self-report (Kappa = 0.08) and air monitor (Kappa = 0.10). In low
      environmental tobacco smoke exposure environments, all three methods for
      measuring exposure may have a role, although modification to monitoring protocols
      will be needed to improve monitoring sensitivity and exposure classification.

PMID- 7503053
TI  - Effects of caffeine consumption on delayed conception.
AB  - The authors examined the effects of caffeine consumption on waiting time to
      conception in the Reproductive Health Study, a retrospective study of 1,430 non
      contracepting, parous women interviewed between July 1989 and June 1990 at
      Fishkill, New York, and Burlington, Vermont. Information was obtained on 2,501
      pregnancies since 1980. Women's reported consumption of caffeinated beverages
      during the first month of pregnancy was used to estimate daily caffeine intake,
      which was categorized as none, 1-150, 151-300, and > or = 301 mg. Information on
      delayed conception was analyzed as a dichotomous variable (< or = 12 months delay
      vs. > 12 months delay), and the per cycle probability of conception
      (fecundability) was estimated using waiting time to conception as a continuous
      variable. Odds ratios of delayed conception and fecundability ratios adjusted for
      age, parity, smoking, last contraceptive used, infertility history, and race,
      were estimated by logistic regression and Cox proportional hazard models,
      respectively. Women who did not smoke and who consumed no caffeine were used as a
      reference group. The adjusted odds ratio of delayed conception for more than one
      year was not increased among women who consumed < or = 300 mg of caffeine daily.
      However, the odds ratio (OR) was 2.65 (95% confidence interval (CI) 1.38-5.07)
      among nonsmokers who consumed > or = 301 mg of caffeine daily. Although smoking
      per se was associated with a significant increased risk of delayed conception (OR
      = 1.77, 95% CI 1.33-2.37), no effect of high caffeine consumption was observed
      among women who smoked. Fecundability was reduced among nonsmokers who consumed
      more than 300 mg caffeine daily (fecundability ratio = 0.74, 95% CI 0.59-0.92).
      Smoking reduced the fecundability ratio, but the authors observed no effect of
      caffeine consumption on fecundability among women who smoked. Other studies
      provide biologic plausibility for these findings. The authors conclude that high
      levels of caffeine consumption may result in delayed conception among women who
      do not smoke cigarettes.

PMID- 7503054
TI  - Estimated timing of mother-to-child human immunodeficiency virus type 1 (HIV-1)
      transmission by use of a Markov model. The HIV Infection in Newborns French
      Collaborative Study Group.
AB  - It has been shown that mother-to-child human immunodeficiency virus type 1 (HIV
      1) transmission can occur both during pregnancy and at delivery, but the
      respective frequencies in these periods are unknown. Moreover, it is difficult to
      determine the timing of mother-to-child HIV-1 transmission by direct sampling.
      The use of an elaborate statistical method is therefore necessary. The authors
      studied 495 consecutive infants born between May 1988 and August 1991 who were
      included, at birth, in the French Prospective Study on Pediatric HIV Infection.
      At least one blood sample was obtained from every infant during the first 14 days
      of life. All samples obtained within 3 months of birth were tested by at least
      two of the following methods: viral culture, polymerase chain reaction (PCR), and
      antigenemia, as well as by Western blot test. Data for the 95 infected infants
      (those seropositive at 18 months and those who died of HIV disease before this
      age), and who were exclusively bottle-fed, were analyzed in a Markov model to
      estimate the timing of viral transmission, the time from birth to the emergence
      of detectable virus, and the time from birth to seroconversion. The model
      indicated that one-third of the infants were infected in utero, less than 2
      months before delivery (95th percentile). In the remaining 65% of cases (95%
      confidence interval (CI) 22-92), the date of infection was estimated as the day
      of birth. The estimated median period between birth and the emergence of viral
      markers was 10 days (95% CI 6-14) and the 95th percentile was estimated at 56
      days. These results support the view that HIV infection can be diagnosed during
      the first 3 months of life. The authors conclude that mother-to-child HIV-1
      transmission appears to occur late in pregnancy or at delivery.

PMID- 7503055
TI  - Model-based estimation of population attributable risk under cross-sectional
      sampling.
AB  - The covariate-adjusted population attributable risk (PAR) measures the
      proportionate reduction in disease prevalence in the target population when the
      putative risk factor is removed, after adjusting for covariate effects. This
      paper extends the model-based approach developed for retrospective and cohort
      studies to the cross-sectional sampling design. An appropriate logit linear model
      is utilized to estimate the covariate-adjusted attributable risk. The asymptotic
      variance of this complex ratio estimate is obtained using Taylor series
      expansions which incorporate the sampling variation of the estimated model
      parameters and the appropriate estimates of risk factor prevalence. These methods
      are illustrated with cardiovascular disease risk factor data from the second
      National Health and Nutrition Examination Survey (NHANES II).

PMID- 7503056
TI  - Re: "Risk of premenopausal breast cancer and use of electric blankets" and "Use
      of electric blankets and risk of postmenopausal breast cancer".

PMID- 7503057
TI  - Re: "Tobacco, alcohol, and colorectal tumors: a multistep process".

PMID- 7503059
TI  - Reduction in recombinant human erythropoietin doses by the use of chronic
      intravenous iron supplementation.

PMID- 7503058
TI  - Re: "Medical practice-based influenza surveillance: viral prevalence and
      assessment of morbidity".

PMID- 7503060
TI  - Reduction in recombinant human erythropoietin doses by the use of chronic
      intravenous iron supplementation.

PMID- 7503061
TI  - Advanced glycosylation end products in diabetic renal and vascular disease.
AB  - An increasing body of experimental data supports the important, etiologic role of
      advanced glycosylation end products (AGEs) in the development of the renal and
      vascular complications of diabetes. Advanced glycosylation end products arise
      from glucose-derived Amadori products and act to increase vascular permeability,
      enhance protein and lipoprotein deposition, inactivate nitric oxide, and promote
      matrix protein synthesis and glomerular sclerosis. Loss of normal renal function
      increases the level of circulating plasma AGEs and contributes markedly to their
      ultimate tissue toxicity. Aminoguanidine, a recently developed pharmacologic
      inhibitor of advanced glycosylation, is presently undergoing phase II/III
      clinical trials in diabetic nephropathy and may offer a specific therapeutic
      modality for diminishing the formation and toxicity of AGEs.

PMID- 7503062
TI  - Status of patients who underwent uninephrectomy in adulthood more than 20 years
      ago.
AB  - We investigated the status of patients without systemic diseases who had
      undergone uninephrectomy for unilateral renal diseases in adulthood more than 20
      years ago at Tokyo Denryoku Hospital. There were 21 participants (mean age +/-
      SD, 58.6 +/- 8.0 years) who fulfilled these criteria. The average interval since
      nephrectomy was 27.9 +/- 6.2 years. The mean current creatinine clearance was
      88.5 +/- 21.2 mL/min/1.73 m2, which is 92.9% of that in healthy age- and sex
      matched controls with two kidneys. The 24-hour urine protein excretion in these
      patients was only slightly higher than in the controls (214 +/- 190 mg v 119 +/-
      62 mg, P = NS). Age at nephrectomy, length of time with a single kidney, or sex
      had little effect on the remnant renal functions. There was a positive
      correlation between current mean arterial pressure and serum creatinine (r =
      0.44, P < 0.05). Patients who developed hypertension after uninephrectomy had a
      family history of hypertension more frequently than those with normotension (86%
      v 29%, P < 0.05). We conclude that (1) renal function after compensatory
      hyperfiltration of more than 20 years due to uninephrectomy for unilateral renal
      diseases in adulthood is well maintained, although hypertension has a
      considerable effect on the renal functions, and that (2) family history of
      hypertension plays a key role in determining the incidence of hypertension even
      in the uninephrectomized patients.

PMID- 7503063
TI  - Acquired oligonephropathy and diabetic nephropathy.
AB  - Congenital or acquired nephron number reduction and diabetes mellitus both induce
      hyperfiltration and intrarenal hypertension. These hemodynamic factors have been
      suggested to play an important role in the initiation and progression of diabetic
      and nondiabetic glomerulopathies. In a prevalence cohort of all 50 albuminuric (>
      or = 300 mg/24 hr), non-insulin-dependent diabetic mellitus (NIDDM) patients
      (aged < 66 years) attending a diabetic clinic during 1987, we identified four
      patients with acquired oligonephropathy who had developed diabetic nephropathy.
      Three patients only had a single functioning kidney (nephrectomy in two cases),
      and the remaining patient had unilateral severely reduced kidney function and
      elevated plasma renin concentration. These patients represent 8% of our NIDDM
      population with albuminuria, and are the only patients in our NIDDM population
      younger than 66 years (n = 363) known to have single kidneys. However, systematic
      renography screening was not performed. During the observation period, which
      ranged from 16 to 100 months, albuminuria increased from 2.3 g/24 hr (range, 1.2
      to 3.4 g/24 hr) to 3.2 g/24 hr (range, 0.7 to 9.4 g/24 hr), glomerular filtration
      rate decreased to 6 mL/min/yr (range, 4 to 12 mL/min/yr), and blood pressure
      remained stable at 142/92 mm Hg. Three patients received antihypertensive
      medication. Two of the patients died after 16 and 26 months of observation,
      respectively, due to acute myocardial infarction and stroke. The results of our
      study of NIDDM patients support the concept that reduced nephron number
      predispose patients to the development of diabetic nephropathy.

PMID- 7503064
TI  - The urine protein to creatinine ratio as a predictor of 24-hour urine protein
      excretion in type 1 diabetic patients with nephropathy. The Collaborative Study
      Group.
AB  - The purpose of this study was to determine the usefulness of a random urine
      specimen protein to creatinine (P/C) ratio in predicting 24-hour urine protein
      excretion (24 UP) in type 1 diabetic patients with overt nephropathy. Two hundred
      twenty-nine outpatient diabetic subjects enrolled in the Collaborative Study
      Group's multicenter clinical trial of "Angiotensin-Converting Enzyme Inhibition
      in Type 1 Diabetic Nephropathy" provided specimens for study, which encompassed a
      wide range of proteinuria (0.05 to 13.3 g/d). Twenty-four hour urine collections
      for total protein and creatinine (g/d) were obtained in the outpatient setting.
      This was followed shortly thereafter by an untimed single urine specimen for
      protein and creatinine (mg/dL). For longitudinal analysis, 33 patients provided
      two 24-hour urine collections with concomitant random urine specimens, separated
      by at least a 3-month period. Across the range of proteinuria that we studied,
      the log random urine P/C ratio correlated to log 24 UP (r = 0.90). The regression
      line was almost identical to the line of unity, which indicates that a patient's
      24 U/P (in g/d) can be predicted directly from the random urine specimen P/C
      ratio (P/C = 24 UP in g/d). However, the standard deviations associated with
      these predictions were large, especially at the higher 24 UP values. Of the 33
      patients who provided two time-separated specimens, the direction of change in
      P/C ratio was discordant with the direction of change in 24 UP in 14 of the 33
      repeat specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503065
TI  - Bicarbonate dialysate for continuous renal replacement therapy in intensive care
      unit patients with acute renal failure.
AB  - Lactate-buffered peritoneal solution traditionally has been used as dialysate for
      continuous renal replacement therapy (CRRT) in the United States because no
      bicarbonate solution is commercially available. Since 1994, the Cleveland Clinic
      Foundation Dialysis Unit has prepared a bicarbonate solution (sodium 144 +/- 3
      mEq/L, HCO3 37 +/- 2 mEq/L, potassium 3 or 4 mEq/L, calcium 3.0 +/- 0.3 mEq/L,
      and magnesium 1.4 +/- 0.3 mg/dL) replicating the dialysate for chronic
      intermittent hemodialysis. No solute precipitation, as calcium or magnesium
      salts, were observed, and several cultures of the solution, performed at various
      time periods, remained negative. Fifty critically ill acute renal failure
      patients have been treated with bicarbonate-CRRT. All patients were in multiple
      organ failure and required mechanical ventilation; 37 were receiving
      vasopressors. Forty-four continuous venovenous hemodialysis sessions and eight
      continuous arteriovenous hemodialysis sessions were performed with a mean
      duration of 7.8 +/- 6.1 days. The mean inflow dialysate rate was 1,249 +/- 225
      mL/hr and the mean outflow rate (dialysate plus ultrafiltration) was 1,399 +/-
      237 mL/hr; the inflow rate was constantly kept lower or equal to the outflow rate
      to avoid an enhanced potential for backfiltration. No related fever spikes or
      sepsis episodes were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503066
TI  - Pharmacologic profile of diaspirin cross-linked hemoglobin in hemodialysis
      patients.
AB  - Various hemoglobin compounds have been evaluated as potential oxygen-carrying,
      blood volume expanders, but toxicity has prevented clinical application.
      Diaspirin cross-linked hemoglobin (DCLHb) represents a modified hemoglobin
      compound that is derived from human red blood cells and maintained in a
      tetrameric configuration by cross-linkages between the two alpha chains of the
      hemoglobin molecule. In a randomized, placebo-controlled, single-blind, cross
      over trial, DCLHb's safety and pharmacologic parameters were evaluated in 18
      subjects receiving chronic hemodialytic therapy. A 30-minute infusion of 25, 50,
      or 100 mg/kg DCLHb or placebo was given at the start of routine hemodialysis. One
      week later, the alternate treatment (placebo or DCLHb) was administered. Maximum
      plasma hemoglobin concentrations and terminal half-life values were calculated
      for each dosage group. Dialysate was collected and assayed for hemoglobin.
      Changes in systolic and diastolic blood pressure from baseline and the volume of
      hypertonic saline administered for treatment of hypotension during hemodialysis
      were measured. The maximum plasma hemoglobin concentrations increased with DCLHb
      dose and occurred at the end of DCLHb infusion. The mean (+/- SD) terminal half
      life ranged from 2.1 +/- 1.0 hours in the 25 mg/kg DCLHb group to 4.3 +/- 1.4
      hours in the 100 mg/kg group, but did not differ significantly between groups.
      Mean baseline plasma hemoglobin corrected areas under the plasma concentration
      time curves increased from 89 to 1,136 mg/hr/dL across the fourfold dose range.
      Diaspirin cross-linked hemoglobin was not dialyzable as none was detected in
      dialysate. The maximum increase in systolic blood pressure from baseline
      increased significantly with DCLHb dose compared with placebo (P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503068
TI  - Proximal tubular cell synthesis and secretion of endothelin-1 on challenge with
      albumin and other proteins.
AB  - Abnormal traffic of proteins through the glomerular capillary has an intrinsic
      renal toxicity possibly linked to the subsequent process of over-reabsorption by
      proximal tubular cells. We investigated in vitro the effect of different protein
      concentrations on proximal tubular cell endothelin-1 (ET-1) synthesis. Rabbit
      proximal tubular RC.SV1 cell line was grown to confluence in serum-free
      hormonally defined medium. Cells were incubated for 6 and 24 hours with serum
      free medium containing bovine serum albumin (BSA, 0.1 to 10 mg/mL). ET-1, a
      locally released hormone that stimulates cell proliferation and promotes
      extracellular matrix protein synthesis, was measured in cell supernatant by
      radioimmunoassay. BSA induced a significant dose-dependent increase in proximal
      tubular cell ET-1 synthesis. BSA and fatty acid-free BSA stimulated tubular ET-1
      synthesis and release to a comparable extent, indicating that the lipid component
      of the molecule is not involved in the observed phenomenon. Experiments in which
      tubular cells grown on filters in bicameral systems were incubated with BSA (10
      mg/mL) showed that ET-1 release was predominantly basolateral. The stimulatory
      effect on tubular ET-1 synthesis and release was not specific to albumin but was
      shared by immunoglobulin (Ig) G and transferrin. Exposure of proximal tubular
      cells for 6 and 24 hours to both proteins (1 and 10 mg/mL) resulted in a dose
      dependent increase in ET-1 synthesis. These data suggest that overexposure of
      proximal tubular cells to proteins, as it occurs in vivo in proteinuric renal
      diseases, may promote excessive tubular synthesis of ET-1, which is mostly
      secreted toward the interstitial compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503067
TI  - In vitro effects of bicarbonate- versus lactate-buffered continuous ambulatory
      peritoneal dialysis fluids on peritoneal macrophage function.
AB  - At present, lactate is the most commonly used buffer in peritoneal dialysis
      fluids (PDFs). The high lactate concentration in combination with low original pH
      was demonstrated to suppress phagocytic function. We evaluated the in vitro
      effects of a newly formulated bicarbonate-buffered PDF containing glycylglycine
      (BiGG15 and BiGG40; Pierre Fabre Medicament, Castres, France) on peritoneal
      macrophage (PMO) function, and compared them with those of equiosmolar lactate
      buffered PDF (1.5% and 4.25% glucose; pH 5.4 and pH 7.4) and control buffer.
      Peritoneal macrophages were isolated from the effluents of 10 continuous
      ambulatory peritoneal dialysis patients and tested for luminol- and lucigenin
      enhanced chemiluminescence, superoxide (O2-) generation measured by cytochrome c
      reduction, killing capacity, and phagocytosis after incubation in the PDF used.
      Exposure of PMO to lactate-buffered PDF with an original pH of 5.4 resulted in a
      significant suppression of all PMO functions measured, compared with bicarbonate-
      and lactate-buffered PDFs with a pH of 7.4. At physiological pH (7.4),
      chemiluminescence generation of PMO exposed to BiGG15/40 was significantly higher
      compared with the corresponding equiosmolar lactate-buffered PDF (1,992 +/- 858 x
      10(3) cpm/10(4) cells v 856 +/- 398 x 10(3) cpm/10(4) cells; P < 0.004). O2-
      generation, killing capacity, and phagocytosis were not significantly different
      after PMO exposure to bicarbonate compared with exposure to lactate-buffered PDF
      with a neutral pH. Irrespective of the buffer used, high-osmolality PDFs
      suppressed PMO function significantly more than low-osmolar PDFs. In conclusion,
      bicarbonate-buffered PDFs are less detrimental to PMO function than lactate
      containing PDFs; these preliminary in vitro results need to be confirmed in vivo.

PMID- 7503069
TI  - Cilazapril delays progression of hypertension and uremia in rat polycystic kidney
      disease.
AB  - Polycystic kidney disease (PKD) is the fourth most common cause of end-stage
      renal disease and is a common cause of hypertension and associated vascular
      morbidity. Activity of the renin angiotensin system has been identified as a
      major component of hypertension and altered fluid and electrolyte physiology in
      PKD. Activity of this pathway also has been proposed as a potential modulator of
      structural change in both tubules and the interstitium of the kidney. Cilazapril
      is a long-acting angiotensin-converting enzyme inhibitor that has been effective
      in producing vascular remodelling in hypertensive vascular disease. We undertook
      a study to determine whether therapy with cilazapril would modify the expression
      of PKD in the Han:SPRD-cy rat, a model of autosomal dominant PKD that closely
      resembles human disease. Male rats were treated for 4 months, starting at 1 month
      of age. Control animals were hypertensive by 3 months of age, whereas treated
      animals were noted to be hypertensive only at the exit assessment (P < 0.001 at 3
      months, P = 0.005 at 5 months). At 5 months of age, cilazapril-treated animals
      had modest but statistically significant reductions in serum creatinine (mean,
      1.77 mg/dL v 1.97 mg/dL; P = 0.0006) and morphometrically assessed cyst volume
      (mean, 0.32 mL v 0.67 mL; P = 0.036). Cilazapril is an effective treatment for
      hypertension in this model of progressive renal disease and may have benefits
      beyond the prevention of cardiovascular morbidity.

PMID- 7503070
TI  - Interstitial nephritis in sarcoidosis: simultaneous multiorgan involvement.
AB  - Two cases of sarcoidosis with interstitial nephritis (lymphocytic and
      granulomatous) are described. In contrast to the majority of reported cases,
      patients simultaneously exhibited renal failure and multiple extrarenal
      manifestations, including bone marrow granulomas. Pretreatment gallium-67 gamma
      scan of the kidneys produced negative results. Patients were treated with
      steroids. Treatment resulted in a normal renal function after 1 year in the
      patient with lymphocytic interstitial nephritis. Renal function improved in the
      patient with granulomatous interstitial nephritis, and a second renal biopsy
      performed 13 months after diagnosis revealed granuloma disappearance and residual
      interstitial fibrosis. These cases provide evidence that interstitial nephritis
      in sarcoidosis may appear simultaneously with multiorgan involvement. The absence
      of gallium-67 renal intake does not guarantee that the disease is not active in
      the kidneys.

PMID- 7503071
TI  - A female heterozygous patient with Fabry's disease with renal accumulation of
      trihexosylceramide detected with a monoclonal antibody.
AB  - We describe a female patient with heterozygous Fabry's disease. The patient had
      persistent proteinuria and microhematuria but lacked any other diagnostic signs
      such as corneal and cutaneous involvement. Kidney tissue obtained at biopsy
      showed the segmentally distributed enlarged glomerular epithelia. These cells
      were filled with vacuolated foamy cytoplasm, which had lamellar and myelinoid
      structures under electronmicroscopic observation. Accumulation of
      trihexosylceramide (CTH) in these foamy epithelial cells was confirmed with
      immunohistochemical staining with the use of anti-CTH monoclonal antibody. Alpha
      galactosidase activity of leukocytes was 67 nmol/mg protein/hr, which was
      approximately half that of the normal population (mean +/- SD, 147 +/- 65 nmol/mg
      protein/hr, n = 20). All of these findings were compatible with the diagnosis of
      heterozygous Fabry's disease. We recommend that kidney tissue biopsy specimens
      suggesting Fabry's disease be immunostained with anti-CTH antibody.

PMID- 7503072
TI  - Progression to calcific mitral stenosis in end-stage renal disease.
AB  - A 59-year-old man with end-stage renal disease and on hemodialysis had neither
      mitral stenosis nor mitral calcification on echo-Doppler examination in 1989, but
      had extensive mitral calcification and definite mitral stenosis on conventional
      and transesophageal echocardiography in 1994. The left ventricle had marked
      concentric hypertrophy. To our knowledge this is the first documentation of the
      development of calcific mitral stenosis in end-stage renal disease revealed by
      serial echo-Doppler studies.

PMID- 7503073
TI  - Metastatic renal carcinoma in a pediatric recipient of an adult cadaveric donor
      kidney.
AB  - A 15-year old male with chronic renal failure secondary to obstructive uropathy
      received an adult cadaveric donor kidney. Evaluation for painless macroscopic
      hematuria occurring 2 years after transplantation disclosed a metastatic renal
      cell carcinoma, which by the use of restriction fragment length polymorphism
      analysis was shown to be of the donor's origin. Transplant nephrectomy and
      cessation of immunosuppressive therapy resulted in complete regression of
      multiple pulmonary metastases.

PMID- 7503076
TI  - Proposed Health Care Financing Administration guidelines for reimbursement of
      enteral and parenteral nutrition.

PMID- 7503074
TI  - A proposed glossary for dialysis kinetics.
AB  - Quantification of the dialysis dose and assessment of nutritional status and
      response to nutritional therapy have become standard parts of the management of
      the chronic dialysis patient. Although advances in these areas have led to a more
      rational basis for therapy, certain misconceptions and points of confusion appear
      to have occurred. Recognizing the importance of a standard nomenclature to the
      development of concepts and the communication of research findings, we have
      attempted to compile a list of terms that are commonly used in the field of
      dialysis. New terms have been proposed for current ones that do not seem
      adequate. In addition, we have discussed potential methodologies for obtaining
      more accurate data for dialysis kinetics and for precise monitoring of
      nutritional intake and status. It is hoped that this glossary will stimulate
      discussion that will lead to refinements in terminology and concepts that will,
      in turn, improve research and practice in nephrology. It is anticipated that many
      of these definitions and recommendations will be modified or superseded as the
      management of patients with renal failure continues to advance.

PMID- 7503077
TI  - The power of physicians: autonomy and balance in a changing system.

PMID- 7503075
TI  - Chemokines and renal disease.
AB  - Chemokines are low molecular weight inflammatory cytokines with chemoattractant
      properties as their major biologic effect. They are classified into at least two
      families. C-X-C chemokines (alpha subfamily) act primarily on neutrophils, while
      C-C chemokines act preferentially on monocytes. Chemokine receptors are G protein
      coupled receptors that form a family of structurally and functionally related
      proteins. Chemokines are induced in cells and tissue in response to
      proinflammatory cytokines. They are produced by glomerular, tubular interstitial,
      and blood vessel cells. There is good evidence that chemokines contribute to
      neutrophil and mononuclear cell infiltration in glomeruli and interstitium. Their
      expression is increased in renal disease, and neutralization studies using
      antibodies in vivo demonstrated a role for certain chemokines in mediating renal
      pathology and proteinuria. Interleukin-8, RANTES, and monocyte chemotactic
      peptide are the best-studied chemokines in the kidney. Development of specific
      antibodies and receptor antagonists should help establish the precise role of
      these mediators in renal disease. Important therapeutic implications may result
      from this work.

PMID- 7503078
TI  - What is it patients want?

PMID- 7503079
TI  - A study of patient satisfaction and adherence to preventive care practice
      guidelines.
AB  - PURPOSE: Patient satisfaction ratings are being used to judge physicians' quality
      of care and to determine physician reimbursement. We therefore studied the
      association between patient satisfaction and the quality of medical care received
      by patients in physicians' offices. PATIENTS AND METHODS: Patient satisfaction
      was measured in a survey of patients cared for by 48 primary care physicians in a
      health maintenance organization in Southern California. Evidence that patients
      were offered or received preventive care services was determined by patient
      survey and medical record abstraction, respectively. The medical records of 3,249
      randomly selected elderly patients (65 to 75 years old) were studied. Of these
      patients, 2,799 completed a patient satisfaction and preventive care services
      survey (response rate 86.1%), 2,654 completed a patient satisfaction survey
      (response rate 81.7%), and 2,258 completed a quality-of-life survey (response
      rate 69.5%). RESULTS: Patients were generally satisfied with their physicians'
      care (median satisfaction score 4.2; scale 1 to 5, 5 being most satisfied).
      Patients who received or were offered mammography, clinical breast examination,
      influenza vaccine, pneumococcal vaccine, tetanus vaccine, exercise counseling,
      and smoking cessation counseling were more satisfied with their medical care than
      those patients who did not (P < 0.001 for all tests). After controlling for the
      physician who was providing the medical care, there was still a statistically
      significant relationship between these factors and patient satisfaction.
      CONCLUSIONS: We found a significant association between patient satisfaction and
      the performance of some but not all preventive care services. However, we cannot
      be certain whether there is a relationship between patient satisfaction and
      quality of patient care.

PMID- 7503081
TI  - Long-term follow-up of endoscopic retrograde cholangiopancreatography
      sphincterotomy for patients with acquired immune deficiency syndrome papillary
      stenosis.
AB  - PURPOSE: To evaluate the long-term effects on biliary-type pain and changes in
      biochemical parameters in patients with AIDS-associated papillary stenosis who
      underwent endoscopic retrograde cholangiopancreatography (ERCP) sphincterotomy.
      PATIENTS AND METHODS: Twenty-five consecutive patients were diagnosed by
      cholangiography with AIDS-associated papillary stenosis using standard criteria.
      Patients underwent ERCP sphincterotomy and were followed prospectively in the
      Gastrointestinal or Liver Clinics, San Francisco General Hospital, and by their
      primary physicians. Post-procedure data was prospectively collected by chart
      review or in-person or telephone interview, and analyzed using statistical
      software. RESULTS: All patients presented with severe right upper quadrant and/or
      mid-epigastric abdominal pain and had marked elevations of serum alkaline
      phosphatase. Following ERCP sphincterotomy, pain scores decreased significantly
      for at least 9 months of follow-up. Serum alkaline phosphatase levels, however,
      remained essentially unchanged. Overall quality of life was difficult to assess,
      as patients suffered from other AIDS-associated debilitating diseases.
      CONCLUSIONS: ERCP sphincterotomy, while not without risks, provided significant
      reduction in pain in patients with AIDS-associated papillary stenosis.

PMID- 7503080
TI  - 25-Hydroxyvitamin D3 reverses alteration of the vitamin D-endocrine system in
      blacks.
AB  - BACKGROUND: Previous findings indicated that serum 25-hydroxyvitamin D and
      urinary calcium are decreased and serum immunoreactive parathyroid hormone, serum
      1,25-dihydroxyvitamin D, and urinary cyclic adenosine 3',5'-monophosphate are
      increased in normal black compared to normal white subjects. Studies were carried
      out to determine if alteration of the vitamin D-endocrine system in blacks is
      reversed by oral supplementation with 25-hydroxyvitamin D3. PATIENTS AND METHODS:
      Eight normal young adult black men and women were admitted two times to a
      metabolic ward for 2.5 days and studied after no treatment and again after
      treatment for 1 week with oral 25-hydroxyvitamin D3, 40 to 60 micrograms/d. Six
      of the subjects underwent a postcontrol study after discontinuation of treatment.
      RESULTS: 25-Hydroxyvitamin D3 treatment significantly increased serum 25
      hydroxyvitamin D and urinary calcium and reduced serum 1,25-dihydroxyvitamin D
      and urinary cyclic adenosine 3',5'-monophosphate, an index of function of
      parathyroid hormone. In a postcontrol study, values for serum 25-hydroxyvitamin
      D, serum 1,25-dihydroxyvitamin D, and urinary calcium had returned to control
      values. CONCLUSIONS: The results provide evidence that reduction of serum 25
      hydroxyvitamin D contributes to or accounts for alteration of the vitamin D
      endocrine system in black subjects.

PMID- 7503082
TI  - Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic
      hypotension.
AB  - PURPOSE: In this double-blind study, the authors compared the safety and efficacy
      of the investigational oral agent midodrine, a specific alpha 1-sympathomimetic
      agent, with ephedrine, a nonspecific alpha- and beta-adrenergic receptor agonist.
      Eight patients (4 men and 4 women) with refractory orthostatic hypotension
      resulting from autonomic failure were studied. This study was based on the notion
      that neurogenic orthostatic hypotension results from attenuation of adrenergic
      nerve traffic and not from alpha-adrenergic receptor dysfunction. Although
      arteriolar vasoconstrictors seem to be appropriate therapeutic agents, their
      success has been limited, and the search for an ideal drug is ongoing. METHODS:
      The authors employed a blocked, double-blind, randomized crossover design. The
      single-blind placebo run-in period was 2 days. The double-blind titration period
      with either midodrine or ephedrine was 3 to 5 days; the titration end point was
      to increase standing systolic blood pressure to > or = 80 mm Hg and to maintain a
      supine pressure below 180/100 mm Hg. The maintenance period was 3 to 5 days. A 4
      day placebo washout period was interposed at the crossover point. RESULTS: The
      ability to stand improved in patients treated with midodrine but not with
      ephedrine. Midodrine significantly increased both systolic (P < 0.001) and
      diastolic (P < 0.001) standing blood pressure over placebo (P < 0.001) and
      ephedrine (P < 0.05). In contrast, ephedrine-induced changes in standing
      pressures did not significantly differ from placebo (P > 0.05). Midodrine
      treatment improved the frequency of the ability to stand as compared with
      ephedrine, and was associated with a significantly higher incidence of standing
      systolic pressures > 80 mm Hg than was placebo (P < 0.001). Both midodrine and
      ephedrine significantly increased supine systolic and diastolic blood pressures
      over placebo (P < 0.001, P < 0.01, P < 0.01, P < 0.01, respectively), but were
      not significantly different from each other. Ephedrine significantly increased (P
      < 0.05) the pulse rate as compared with placebo and midodrine, whereas midodrine
      produced a statistically significant (P < 0.05) but clinically minimal decrease
      in pulse rate compared with placebo. Neither drug affected clinical laboratory
      variables. CONCLUSIONS: Midodrine safely and effectively improved orthostatic
      hypotension caused by autonomic failure. Our data suggest that the ability to
      stand is improved better by midodrine than by ephedrine.

PMID- 7503083
TI  - Increased norepinephrine variability in patients with sleep apnea syndrome.
AB  - OBJECTIVE: To assess the plasma arterial catecholamine response to nocturnal
      desaturation in a group of patients with a history suggestive of sleep apnea.
      PATIENTS AND METHODS: At a Veterans Affairs hospital, 10 patients who had a
      history consistent with sleep apnea syndrome were involved in the study. Arterial
      plasma catecholamines were measured at varying intervals during a 5 1/2-hour
      sleep study. Eighteen samples per patient were analyzed. RESULTS: As the
      hemoglobin saturation decreased, the variability in plasma norepinephrine
      increased significantly (r = -.78, P = 0.004). As the hemoglobin saturation fell,
      there was a trend towards higher concentrations of plasma norepinephrine (r = 
      .53, P = 0.06). As the hemoglobin saturation decreased, the variability in plasma
      epinephrine concentration was not significant (r = .42). CONCLUSION: The
      association between the degree of desaturation and the variability in
      norepinephrine suggests that norepinephrine is released in response to nocturnal
      desaturation.

PMID- 7503084
TI  - Iron overload in African Americans.
AB  - PURPOSE: Iron overload unexplained by dietary or medicinal iron excess,
      transfusion, or sideroblastic anemia has been described infrequently in Americans
      of African descent. The purpose of this study was to characterize iron overload
      attributable to excessive iron absorption in African Americans. PATIENTS AND
      METHODS: In a community hematology and medical oncology practice during the
      interval 1990 to 1993, we identified and evaluated a series of cases comprised of
      6 men and 1 woman, with a mean age of 55 +/- 14 (SD) years (range 33 to 69). Data
      on clinical features, serum iron parameters, liver and body iron stores,
      evaluations of anemia, human leukocyte antigen (HLA) typing, and family studies
      were analyzed. RESULTS: Among our patients, the serum iron parameters were: iron
      concentration 26 +/- 13 mumol/L, transferrin saturation 59 +/- 21%, and ferritin
      concentration 1,588 +/- 1,053 micrograms/L. Clinical abnormalities observed
      included weakness and fatigue, decreased libido and impotence, hepatopathy,
      arthropathy, diabetes mellitus, hypogonadotrophic hypogonadism, and
      hyperpigmentation. Hepatic parenchymal cell iron deposits were increased in each
      of the 6 patients studied, and Kupffer cell iron deposits were prominent in 4.
      The occurrence of iron overload was verified by liver iron quantification and
      therapeutic phlebotomy. Four subjects had alpha-thalassemia minor; 2 others had
      hemoglobin S and C traits. No proband had HLA-A3 positivity. Four probands had
      other family members with iron overload. CONCLUSIONS: In comparison with
      Caucasians with hemochromatosis, our patients have slightly lower mean values of
      serum iron concentration and transferrin saturation, more Kupffer cell iron
      deposits, a higher incidence of thalassemia and hemoglobinopathy, and infrequent
      positivity for HLA-A3. Iron overload in African Americans appears to be more
      similar to that in certain sub-Saharan African natives than to hemochromatosis.

PMID- 7503085
TI  - Anticardiolipin antibodies in systemic lupus erythematosus: clinical and
      laboratory correlations.
AB  - PURPOSE: To examine the link between anticardiolipin antibodies and the features
      of antiphospholipid syndrome in patients with systemic lupus erythematosus (SLE).
      PATIENTS AND METHODS: In this prospective cohort study conducted in a single
      center, 390 SLE patients were followed up between June 1991 and 1994. At each
      assessment, a complete history, physical examination, and laboratory evaluation
      (including measurement of anticardiolipin antibodies) were performed according to
      a standard protocol. RESULTS: Forty-seven percent of the patients had an elevated
      level of anticardiolipin antibodies. In the univariate analysis, elevated
      anticardiolipin antibody levels were found to correlate with thrombocytopenia (P
      = 0.006), prolonged activated partial thromboplastin time (aPTT) (P = 0.003), and
      positive direct and indirect Coombs' test result's (P < 0.001). No correlation
      was identified with any of the clinical features of antiphospholipid syndrome. In
      the multivariate analysis, anticardiolipin antibodies remained highly associated
      with thrombocytopenia (odds ratio [OR] 4.05, P = 0.02), positive direct Coombs'
      test (OR 2.31, P < 0.001), and prolonged aPTT (OR 1.73, P = 0.03). In the
      multivariate model using venous/arterial thrombosis as the outcome variable, only
      prolonged aPTT was associated with venous/arterial thrombosis (OR 7.9, P <
      0.001). None of the laboratory variables were found to correlate with fetal loss.
      CONCLUSIONS: The presence of anticardiolipin antibodies in patients with SLE is
      associated with prolonged aPTT, thrombocytopenia, and positive Coombs' test
      result, but not with antiphospholipid syndrome. Prolonged aPTT is strongly
      associated with venous/arterial thrombosis.

PMID- 7503086
TI  - Hospitalized congestive heart failure patients with preserved versus abnormal
      left ventricular systolic function: clinical characteristics and drug therapy.
AB  - PURPOSE: To compare clinical characteristics of and pharmacologic therapy for
      hospitalized patients with congestive heart failure (CHF) and left ventricular
      systolic dysfunction or normal left ventricular systolic function. PATIENTS AND
      METHODS: Medical records were reviewed for all patients discharged with a
      principal diagnosis of CHF from a university hospital and a community hospital
      between September 1, 1991 and August 31, 1992. Pertinent medical history items
      and prescribed drug therapies at discharge were recorded for each patient's first
      calendar year admission. Patients were categorized as having either normal left
      ventricular systolic function or systolic dysfunction based on the results of
      echocardiography and radionuclide angiography or contrast ventriculogram.
      RESULTS: Of 298 patients with CHF, 92 (31%) had normal left ventricular systolic
      function. Patients with normal systolic function were older, were more often
      women, were less likely to have a history of coronary artery disease, and were
      more likely to have a history of hypothyroidism than patients with systolic
      dysfunction. However, the prevalence of clinical characteristics overlapped
      considerably between the two groups. Among patients with systolic dysfunction,
      79% were discharged on a therapeutic regimen of digoxin, 65% on an angiotensin
      converting enzyme inhibitor, and 26% on either a beta-blocker or a calcium
      channel blocker. Among patients with normal systolic function, 50% were
      discharged on a regimen of a beta-blocker or a calcium channel blocker and 38%
      were discharged on digoxin. Twenty-six percent of patients with normal systolic
      function and without a history of atrial fibrillation were discharged on a
      digoxin regimen. CONCLUSION: Hospitalized CHF patients with normal left
      ventricular systolic function and those with diminished left ventricular systolic
      function share many clinical features. Since recommended drug therapy and
      prognosis differ, our data underscore the importance of diagnostic testing to
      assess left ventricular systolic function. Drug therapy for CHF patients provides
      a major challenge for quality-of-care improvement.

PMID- 7503088
TI  - Controversies in the management of cold, hot, and occult thyroid nodules.
AB  - Some aspects of thyroid nodule evaluation and management remain controversial.
      Radionuclide scanning provides functional information about nodules and
      differentiates cold from hot nodules. Although thyroid cancers are cold on scan,
      most cold nodules are benign. Ultrasonography visualizes the thyroid gland and
      nodules with remarkable clarity and provides structural information about
      location, number, size, and consistency of nodules. Widespread application of
      ultrasonography has resulted in the frequent discovery of incidental (occult)
      nodules in the general population. The clinical significance of these nodules
      remains unknown, and their management has created a dilemma for physicians.
      Current cost-effective evaluation of nodules does not include scanning or
      ultrasonography as routine frontline tests. In most centers, fine-needle
      aspiration biopsy has supplanted imaging studies as the routine initial procedure
      for differentiating benign from malignant nodules. Cytologic diagnosis is
      reliable and inexpensive, and it results in a better selection of patients for
      surgery. Limitations include false-negative diagnoses, nondiagnostic results, and
      indeterminate "suspicious" results. Laboratory test results are usually normal,
      but determination of serum thyrotropin may identify a hot nodule, and plasma
      calcitonin may help diagnose medullary thyroid carcinoma. Treatment of thyroid
      nodules is controversial. In some practices, benign colloid nodules are treated
      with suppressive doses of levothyroxine. Recent reports cast doubt on the
      efficacy of this approach, and it is no longer acceptable to select patients for
      surgical treatment on the basis of suppressive therapy. Furthermore, suppressive
      levothyroxine therapy may be associated with significant bone and cardiac side
      effects, especially in elderly patients and postmenopausal women. Our approach is
      observation for most patients, and we suggest a careful risk-benefit analysis
      when suppression is considered. Hot (autonomous) nodules can be treated with
      radioiodine, surgery, or ethanol injection. The use of sensitive thyrotropin
      assays has revealed that the "euthyroid" hot nodule is often associated with
      subclinical hyperthyroidism, warranting treatment if risks of osteoporosis are
      significant. Small (< 1.5 cm) occult nodules can be observed. Larger (> 1.5 cm)
      nodules can be selectively evaluated by ultrasonographically guided fine-needle
      aspiration. It is prudent to consider cost of care, risk-benefit analysis, and
      the low incidence of malignancy in thyroid nodules when diagnostic tests are
      selected and the treatment plan is outlined.

PMID- 7503090
TI  - Cutaneous paraneoplastic syndromes in solid tumors.
AB  - OBJECTIVE: To provide an overview of the clinical manifestations,
      pathophysiology, and oncologic implications of the cutaneous paraneoplastic
      syndromes that occur predominantly in patients with solid tumors. METHODS: A
      review was performed of the literature identified by a comprehensive MEDLINE
      search. RESULTS: Diverse cutaneous paraneoplastic syndromes may be associated
      with underlying tumors. They include musculoskeletal disorders (clubbing,
      hypertrophic osteoarthropathy, dermatomyositis, and multicentric
      reticulohistiocytosis), reactive erythemas (erythema gyratum repens and
      necrolytic migratory erythema), vascular dermatoses (Trousseau's syndrome),
      papulosquamous disorders (acanthosis nigricans, tripe palms, palmar
      hyperkeratosis, acquired ichthyosis, pityriasis rotunda, Bazex's syndrome, florid
      cutaneous papillomatosis, the sign of Leser-Trelat, and extramammary Paget's
      disease), and disorders of hair growth (hypertrichosis lanuginosa acquisita). The
      clinical manifestations of these dermatoses may precede, coincide with, or follow
      the diagnosis of cancer. The presence of a cutaneous paraneoplastic syndrome is
      often associated with a poor prognosis. CONCLUSIONS: Cutaneous paraneoplastic
      syndromes are specific constellations of mucous membrane and/or skin
      abnormalities that are caused by an underlying tumor. Since they may be the
      presenting sign of an occult cancer, cognizance of their features and clinical
      implications are of considerable importance. Individuals with these syndromes
      should have a thorough workup for an associated malignancy.

PMID- 7503087
TI  - The effect of the antiestrogen tamoxifen on bone mineral density in normal late
      postmenopausal women.
AB  - PURPOSE: To assess the effect of the antiestrogenic agent tamoxifen on bone
      mineral density in normal late postmenopausal women. METHODS: A randomized,
      double-blind, placebo-controlled trial was performed with 57 healthy, late
      postmenopausal women (mean 11 +/- 7 years since menopause). Subjects were
      assigned to take either tamoxifen 20 mg/d or placebo for 2 years. Total body,
      lumbar spine, and proximal femoral (femoral neck, Ward's triangle, trochanter)
      bone mineral densities were measured every 6 months using dual-energy x-ray
      absorptiometry. Serum and urine indices of bone turnover were measured at
      baseline, 6 months, and 2 years. RESULTS: In the women given tamoxifen, the mean
      bone mineral density of the lumbar spine increased by 1.4%, while that in the
      women given placebo declined by 0.7% (P < 0.01 for difference between groups).
      Total body bone mineral density declined in both groups, but less so in the
      tamoxifen-treated women (P < 0.05). At both sites, the effect of tamoxifen was
      maximal after 1 year, with no further separation of the groups thereafter. There
      was no significant effect of tamoxifen on bone mineral density in the proximal
      femur. Tamoxifen produced significant falls in serum alkaline phosphatase (P <
      0.0001), ionized calcium (P < 0.0001), and phosphate (P < 0.01), and in urinary
      excretion of hydroxyproline, n-telopeptides, and calcium (P < 0.05 for each).
      CONCLUSIONS: In normal late postmenopausal women, tamoxifen at a dose of 20 mg/d
      exerts a small protective effect on bone mineral density, comparable in magnitude
      to that of calcium supplementation and less than that of either estrogen or the
      bisphosphonates. Tamoxifen is unlikely to supersede any of these therapies in the
      management of postmenopausal osteoporosis.

PMID- 7503089
TI  - Protocol therapy for acute asthma: therapeutic benefits and cost savings.
AB  - BACKGROUND: To evaluate the therapeutic and financial benefits of protocol
      therapy for acute asthma using standard medications. MATERIALS AND METHODS: This
      study employed a sequential design in which the influence of an asthma care path
      on hospital admissions, length of stay (LOS) in the emergency department, and
      return visits were evaluated for 1 year. This information was contrasted with
      similar data obtained from the 8 months immediately before the protocol was
      implemented (preprotocol) and a 12-month period after strict adherence to it had
      declined (admixture). RESULTS: In all, 526 acute exacerbations of asthma were
      treated with the care path, and 429 and 558 episodes were evaluated during the
      preprotocol and admixture periods, respectively. There were no significant
      differences between the presenting clinical or physiologic features of any group.
      With the protocol, 77% of the patients resolved their symptoms within 1:47 +/-
      0.02 hours:minutes of arrival in the emergency department with a 2% return rate
      within 24 hours. The algorithms used quickly identified those needing
      hospitalization. Patients not meeting the criteria for discharge after receiving
      the treatments employed typically did not resolve their symptoms for days
      (average hospital stay 4.1 +/- 0.2 days). Compared with the preprotocol period,
      the care path significantly reduced the LOS by 50 minutes, the number of urgent
      and intensive care unit admissions by 27% and 41%, respectively, and the
      frequency of return visits within 24 hours by 66%. Charges to patients and third
      party payors decreased $395,000. When adherence to the protocol diminished, LOS,
      admissions, and returns rose significantly toward preprotocol values and the
      financial benefits were lost. CONCLUSIONS: Asthma protocol therapy, based
      primarily upon aggressive use of sympathomimetics in association with serial
      monitoring of key indices of improvement, provides prompt and efficient relief
      for acute exacerbations of asthma. Such an approach yields significant financial
      benefit while quickly identifying individuals who require hospitalization, and it
      also detects physician practice patterns that can have potentially detrimental
      impacts on patient care.

PMID- 7503091
TI  - The teaching of cellular and molecular biology: a survey of program directors in
      internal medicine.
AB  - PURPOSE: Although there has been an explosion in our knowledge of cellular and
      molecular biology, it is unclear if medical students entering internal medicine
      residency programs have been adequately trained in these basic sciences. To
      ascertain the perceived importance of these subjects to the practice of medicine
      and to determine if medical schools are properly training their students, a
      survey was sent to internal medicine program directors. METHODS: A survey was
      sent to 401 internal medicine program directors. Repeat questionnaires were sent
      if no response was received within 6 months. RESULTS: Questionnaires were
      returned by 309 program directors (77%). Only 41% of the program directors felt
      that their residents had received adequate training in cellular and molecular
      biology. Directors of university programs were significantly more likely to think
      that knowledge of these sciences was essential to the practice of medicine and
      that their residents were inadequately trained than directors from nonuniversity
      programs. Only 30% of programs offered any formal training in these sciences.
      CONCLUSION: Medical schools need to reevaluate their curricula in order to
      integrate the basic sciences into all 4 years. Training in these sciences,
      however, should not stop with graduation. The importance of a knowledge of these
      sciences should be emphasized at all training programs.

PMID- 7503092
TI  - Treatment of inherited coagulation disorders.
AB  - Inherited coagulation protein deficiencies associated with bleeding diatheses may
      present with spontaneous bleeding early in life, or may not be recognized until
      the development of hemorrhage after trauma or surgery. Diagnostic evaluation with
      coagulation screening tests, followed by confirmation with coagulation factor
      assays, is essential for appropriate management. For moderate-to-severe
      hemophilia, treatment includes coagulation factor replacement with purified,
      plasma-derived coagulation factor, or in the case of hemophilia A, factor VIII
      concentrate produced with recombinant techniques. Increased use of pharmacologic
      agents such as desmopressin acetate for patients with mild hemophilia A or type 1
      von Willebrand's disease has allowed physicians to treat patients without the
      risk of infectious complications from plasma-derived factor concentrates. In
      addition to the management of the inherited bleeding disorders, patients may also
      require management of human immunodeficiency virus infection, hepatitis, and
      coagulation factor inhibitors. Issues for the coming years will include continued
      work to ensure product safety, the role of prophylactic treatment to prevent
      longterm disabilities, and the application of gene therapy to the management of
      bleeding disorders.

PMID- 7503093
TI  - Chronic intermittent intravenous insulin therapy corrects orthostatic hypotension
      of diabetes.

PMID- 7503094
TI  - Angioedema associated with sumatriptan administration.

PMID- 7503095
TI  - Depressed hepatic dihydropyrimidine dehydrogenase activity and fluorouracil
      related toxicities.

PMID- 7503096
TI  - Head-up tilt testing: do we need to give an added push?

PMID- 7503097
TI  - Osteopenia in adults with cystic fibrosis.

PMID- 7503098
TI  - Serious adverse events with low-dose, long-term corticosteroid therapy in
      rheumatoid arthritis.

PMID- 7503099
TI  - Omeprazole for the treatment of posterior laryngitis.

PMID- 7503101
TI  - Isolated reduction in single-breath diffusion capacity in young, healthy,
      asymptomatic women.
AB  - The clinical significance of an isolated reduction in the carbon monoxide
      diffusing capacity (DLCO) in nonsmoking, asymptomatic individuals is not known.
      Whether a reduced DLCO despite otherwise normal pulmonary function tests warrants
      further investigation remains unanswered. In this article, the authors describe
      five healthy, asymptomatic, young women who had isolated, reduced DLCO and
      subsequent follow-up examinations over a span of 6 years. This case series lends
      support to the contention that an isolated low DLCO in asymptomatic subjects is
      not clinically significant and does not necessitate additional medical inquiry.

PMID- 7503100
TI  - Cancer in families with systemic sclerosis.
AB  - In recent reports, researchers described an increased incidence of cancer in
      patients with systemic sclerosis (SScl). For this article, the authors
      investigated the frequencies of cancer in first-degree relatives of patients with
      SScl in a case-control family study. Information was obtained by personal
      interview of the probands. Fifty-three subjects with cancer were reported among
      814 relatives of patients, compared with 17 subjects among 860 relatives of age-
      and sex-matched control subjects (age and sex adjusted odds ratio = 3.79, 95%
      confidence interval = 2.16-6.66, P < 0.001). Forty-six patients (27.7%) had one
      or more relatives with cancer, compared with 15 control subjects (9%). Within the
      limitations of the methods used, the researchers found an increased risk for
      cancer in first-degree relatives of patients with SScl. This suggests that a
      common genetic or environmental factor may be involved in the development of both
      cancer and SScl.

PMID- 7503102
TI  - Observations on nursing home residents with a history of hip fracture.
AB  - The authors evaluated nursing home residents with a prior history of hip fracture
      for osteopenia and its risk factors, and attempted to learn to what extent the
      residents' bone status had been considered by their primary care physicians.
      Thirty-one hip fracture residents in the Milwaukee VA nursing home were studied
      to determine their status with regard to bone mineral density of the proximal
      femur, and the following risk factors or predictors of osteopenia: history of
      smoking; history of fractures; calcium and vitamin D intake; underweight;
      immobility; hypogonadism; and administration of drugs that may accelerate bone
      demineralization. Data were also collected on the evaluation and management of
      the post hip fracture residents in three other nursing homes. In the Milwaukee
      nursing home, out of 31 hip fracture survivors, 74% had sustained a hip fracture
      before admission to the nursing home; 29% had a history of second fracture. In
      84% of patients, there was no mention of osteopenia in the active medical problem
      list and, therefore, there was no intervention plan in place to improve or
      prevent further bone loss. Thirty-two percent were underweight, 36% were
      currently smoking, 55% were immobile, 64% were consuming at least one medication
      that might increase bone loss, calcium intake was less than 1,000 mg daily in
      52%, and 66% were hypogonadal (serum testosterone level less than 300 ng/dL).
      Chart reviews of the hip fracture survivors at three other nursing homes revealed
      similar findings. Approximately 5-15% of nursing home residents are hip fracture
      survivors. They usually have severe osteopenia and multiple risk factors for
      further bone loss and future fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503103
TI  - Vasoactive agents modulate matrix metalloproteinase-2 activity by mesangial
      cells.
AB  - Vasoactive agents alter proteinuria by modulating glomerular hemodynamics. The
      authors hypothesized that vasoactive agents may be altering degradation of the
      collagen component of glomerular basement membrane, which also may be
      contributing to proteinuria. Mesangial cells treated with 10(-6) M angiotensin II
      had higher (P < 0.01) metalloproteinase activity (MA) when compared with control
      cells. This effect of angiotensin II was dose dependent. Amlodipine (10(-6) M), a
      calcium channel blocker, inhibited MA (control, 5.86 +/- 0.08 microgram versus
      4.13 +/- 0.06 microgram gelatin degraded/mg protein, P < 0.001). The decrease in
      mesangial MA caused by amlodipine also occurred in a dose dependent manner.
      Amlodipine attenuated (P < 0.05) angiotensin II-stimulated MA (control, 6.69 +/-
      0.30 micrograms, angiotensin II, 10.68 +/- 0.49 micrograms, angiotensin
      II+amlodipine 8.29 +/- 0.30 micrograms gelatin degraded/mg protein).
      Prostaglandin E2 increased (P < 0.001) MA (control, 10.22 +/- 0.9 micrograms
      versus prostaglandin E2, 17.9 +/- 0.9 micrograms gelatin degraded/mg protein),
      whereas indomethacin, a prostaglandin inhibitor, attenuated the metalloproteinase
      activity (control, 9.67 +/- 0.32 micrograms vs. 10(-6) M indomethacin, 4.22 +/-
      0.31 micrograms gelatin degraded/mg protein, P < 0.001). Indomethacin also
      inhibited angiotensin II-stimulated MA (angiotensin II, 18.66 +/- 0.46 vs.
      angiotensin II+indomethacin, 11.86 +/- 0.56 micrograms degraded/mg protein, P <
      0.001). Similarly, meclofenamate, another prostaglandin inhibitor, attenuated (P
      < 0.001) angiotensin II-induced MA. Because angiotensin II increases
      prostaglandin E2 synthesis by mesangial cells, it appears that increased MA,
      induced by angiotensin II, may be mediated partly through the generation of
      prostaglandin E2.

PMID- 7503104
TI  - Lack of effect of exercise training on dehydroepiandrosterone-sulfate.
AB  - Although functions of dehydroepiandrosterone (DHEA) and its sulfate ester are
      unknown, investigators have found an inverse relation between DHEA-sulfate levels
      and coronary artery disease, suggesting its importance as an inverse coronary
      risk factor. In previous studies, where behavioral therapy was used to try to
      reduce stress and social isolation, DHEA levels increased--although other
      confounding factors, including enhanced physical activity, also were affected. To
      determine the influence of physical activity alone on plasma DHEA-sulfate levels
      in patients with coronary artery disease, the authors studied the effects of
      exercise training by measuring plasma DHEA-sulfate levels and other parameters in
      96 patients at baseline and after 12 weeks of cardiac rehabilitation and exercise
      training. They confirmed that DHEA-sulfate levels decreased with age (r = 0.41; P
      < 0.0001) and that DHEA-sulfate levels correlated with body mass index (r = 0.32;
      P < 0.001), but not with other baseline risk factors. Exercise training during
      cardiac rehabilitation resulted in a 43% increase in exercise capacity (P <
      0.0001) and was associated with improvement in other cardiac risk factors;
      however, there were no significant changes in plasma DHEA-sulfate levels (106 +/-
      77 micrograms/dL versus 102 +/- 76 micrograms/dL). Although behavior therapy in
      combination with exercise training was shown to lead to concomitant increases in
      DHEA-sulfate and physical activity, exercise training alone has no significant
      impact on DHEA-sulfate, thereby strengthening the suggested role of behavioral
      changes in modifying this hormone.

PMID- 7503105
TI  - Special article: increasing the number of generalist physicians--a new regulatory
      paradigm.
AB  - Increasing the number of generalist physicians has become a major component of
      health system reform proposals. This change in physician manpower may be
      attempted by educational approaches, market-driven responses, or regulatory
      requirements. Regulatory approaches may be considered in the broad contexts of
      public policy models. Two such models considered in this essay include 1) the
      acceptance of health care as a positive claim right that places the
      responsibility for providing health care on the state, and 2) a shift in the role
      of government in general from reacting to public concerns to activity shaping
      them. Each results in a greater governmental, regulatory intervention on medical
      manpower planning. As these policy constructs gain or lose force or favor, so too
      will their impact on medical education.

PMID- 7503106
TI  - Pneumatosis cystoides intestinalis in progressive systemic sclerosis: a case
      report and literature review.
AB  - Pneumatosis cystoides intestinalis (PCI) is an uncommon disease manifestation
      characterized by the presence of air in the bowel wall. It is a benign condition
      that often responds to conservative management; however, it may be a harbinger of
      end stage disease, particularly in progressive systemic sclerosis. The authors
      report a case of pneumatosis cystoides intestinalis in a patient with progressive
      systemic sclerosis in the setting of mixed connective tissue disease that
      responded to conservative treatment. They review the current literature on
      pneumatosis cystoides intestinalis, focusing on possible etiologies and potential
      therapies.

PMID- 7503107
TI  - Case report: multiple myeloma presenting as a diastolic heart failure with no
      evidence of amyloidosis.
AB  - The development of severe right sided congestive heart failure led to a diagnosis
      of immunoglobulin G (lambda) myeloma with a predominance of light chains. Cardiac
      catheterization and endomyocardial biopsy showed a severe diastolic dysfunction
      of both right and left ventricles and extensive myocardial infiltration by
      intercellular fibrillar tissue, which was not amyloid. This is a rare
      presentation of immunoglobulin deposition disease associated with immunocytic
      dyscrasias.

PMID- 7503108
TI  - Massive overdose of sustained-release verapamil: a case report and review of
      literature.
AB  - Verapamil 99 is a commonly prescribed medicine for treatment of hypertension,
      angina, and migraine headache. Toxicity with sustained-release verapamil may be
      prolonged, and manifest with hypotension, bradycardia, metabolic acidosis, and
      hyperglycemia. Currently, because of the lack of a specific antidote management
      of verapamil, toxicity is mainly supportive. Treatment with inotropic support,
      glucagon, calcium, and cardiac pacing may be effective in some cases. A review of
      20 cases and a case report of sustained-release verapamil overdose are described.
      The authors describe a patient who ingested 24 g of slow-release verapamil. This
      is the largest overdose of sustained-release verapamil reported in English
      literature. The patient was managed aggressively with gastric lavage, inotropic
      support, and continuous infusion of calcium and glucagon. The patient's survival
      may have been due to the continuous intravenous calcium gluconate and glucagon
      infusion. Both of these treatment modalities should be considered in patients
      with moderate to severe calcium channel blocker overdose.

PMID- 7503109
TI  - Review: selective filtration--a phlebotomy strategy for sickle cell therapy.
AB  - The molecular defect in sickle cell disease is an error in the coding for
      hemoglobin synthesis. All of a patient's erythrocyte precursors share the genetic
      defect, but the patient's circulating erythrocytes are heterogenous in their
      degree of deformability. Periodic removal, by selective filtration, of the least
      deformable of the circulating erythrocytes might prove of clinical benefit.

PMID- 7503110
TI  - Introduction to the symposium celebrating the Bogalusa Heart Study.

PMID- 7503112
TI  - The benefits of physical activity in childhood.
AB  - Research shows regular exercise/physical activity provides substantial benefits
      in reducing morbidity and mortality from several chronic diseases in adults,
      particularly cardiovascular disease. Observations on levels of fitness and
      activity of children are just being developed with regard to cardiovascular risk.
      Current studies indicate that today's children are probably less fit than
      children 20 years ago. Children are heavier and tend to be more overweight and
      sedentary than earlier. The relationships between fitness and cardiovascular risk
      factors in children are very similar to those in adults. Those children who
      perform better on standardized fitness tests have more favorable body composition
      and lipid profiles. Because cardiovascular risk factors, including obesity, tend
      to track from childhood to adulthood, programs to increase regular physical
      activity in youths hold promise in reducing adult cardiovascular diseases.
      Positive long-term lifestyle changes need to be established early. Data from the
      Heart Smart Superkids/Superfit exercise program show that comprehensive school
      based health promotion and education interventions can improve fitness in
      children and ultimately yield improvements in risk factor profiles.

PMID- 7503111
TI  - Dietary studies of children and young adults (1973-1988): the Bogalusa Heart
      Study.
AB  - The link between diet, the maintenance of health, and the development of chronic
      disease has become increasingly evident in recent years. The advice from national
      health organizations has become more focused, identifying dietary excesses of
      energy, total fat, saturated fatty acids, and dietary cholesterol as adversely
      affecting the health of Americans. In addition, eating habits formed during
      childhood have a potential lifelong effect on serum lipid levels, and thus,
      indirectly, on adult coronary heart disease risk. Therefore, an understanding of
      the diet and nutritional habits of children and young adults is critical to the
      planning of intervention strategies toward the natural course of coronary heart
      disease. For more than 20 years, the Bogalusa Heart Study has been collecting
      dietary data on subjects from infancy through adulthood. The dietary studies have
      described dietary patterns and nutrient intakes, relationships, and tracking of
      serum lipid and lipoprotein levels in a biracial, well defined population. These
      data have provided the rationale for the development of healthy eating habits
      early in life and ultimately the reduction of morbidity and mortality from
      cardiovascular disease.

PMID- 7503114
TI  - From the discovery of risk factors for coronary artery disease to the application
      of preventive measures.
AB  - Hyperlipidemia and high blood pressure have clearly evolved as major risk factors
      for cardiovascular diseases. High fat intake, obesity, and cigarette smoking have
      been shown to be root causes of such risk. Ecologic correlations and case-control
      studies have provided evidence that hyperlipidemia and obesity certainly have
      their beginnings during childhood, and that the onset of cigarette smoking at a
      young age escalates the risk for coronary artery disease. Thus, preventive
      measures will have the greatest impact when applied at an early age. In fact,
      several fine comprehensive school health education programs (eg, Health
      Ahead/Heart Smart, Know Your Body) have demonstrated that behavior can be changed
      and that the risk factors for heart disease can be reduced. Such programs are
      most cost effective when they are multifactorial in nature and address health
      promotion on a broad scale. Therefore, comprehensive school health education
      programs should be a component of national health-care reform. The investment in
      early health education will pay off by deterring chronic diseases in adulthood
      and will thus contribute to a healthier nation.

PMID- 7503113
TI  - Understanding the development of behavior risk factors for cardiovascular disease
      in youth: the Bogalusa Heart Study.
AB  - Lifestyle behaviors, societal structure and process, as well as psychological
      functioning are critical for a comprehensive understanding of the development,
      progression, and potential interventions for cardiovascular disease in children
      and young adults. Several behavior factors emerge as mediators of pathogenesis,
      either alone or in interaction with biologic processes as major contributors. In
      the Bogalusa Heart Study, four of these behaviors are identified that relate
      either directly or indirectly to the development of cardiovascular disease. They
      are tobacco, alcohol, oral contraceptive (OC) use, and type A behavior pattern.
      Limitation of space allows for only a brief review of previous work. The purpose
      of this report is to give a general overview of the research questions,
      methodology, measurements, and analysis of some of these behaviors. Because the
      Bogalusa Heart Study has a cross-sectional and longitudinal design, the study of
      the influence of lifestyle factors on the development of heart disease from early
      childhood remains a work in progress. A full understanding of the development of
      heart disease from childhood so that effective interventions can be designed
      remains elusive.

PMID- 7503115
TI  - Roles of nurses and health workers in cardiovascular health promotion.
AB  - Community-based nurses and health workers who supplement physician office-based
      practice are known to be effective in promoting cardiovascular health. They
      enhance the effectiveness of programs to influence individual and population
      lifestyles, self-care practices, and long-term adherence to recommendations. As a
      team they are able to focus on economic, psychosocial, and behavioral factors in
      culturally relevant ways, often missed in traditional medical care, by attending
      comprehensively to education, income, employment status, living arrangements, and
      daily needs. Much can be learned about these teams from the past by reviewing the
      roles, supporting data, and practice-related issues. There are two important
      points to be made about the nurse and the community health worker in
      cardiovascular health promotion: (1) these roles are not new; and (2) reported
      control rates for high blood pressure and other risk factors are highest when
      multidisciplinary teams help patients actively participate in the
      treatment/prevention program. Promoting cardiovascular health across all segments
      of society with greater emphasis on prevention will require that the barriers to
      interdisciplinary collaboration and full community partnership be reduced or
      eliminated.

PMID- 7503116
TI  - Health ahead--the Heart Smart Family approach to prevention of cardiovascular
      disease.
AB  - The Heart Smart Family Health Promotion program is a unique approach to education
      and skills development aimed at improving the cardiovascular health of entire
      families. By including the entire family system, rather than singling out one
      individual for behavior change, social support and self-confidence are enhanced
      and the probability for maintenance of behavioral skills is increased. The Family
      Health Promotion program uses a format that minimizes lecture and maximizes
      awareness, skills development, problem-solving, and real-life application over a
      12- to 16-week agenda. Behavioral counseling and contingency contracting provide
      opportunities for the practice and reinforcement of new behaviors. Initial
      evaluations of the program model developed with cardiovascular high-risk children
      and their parents indicated that parents significantly increased health
      knowledge, lowered blood pressure, became more physically active, and decreased
      their intake of total fat, saturated fat, and sodium. A clinically significant
      reduction in children's blood pressure also was observed. Children's weight
      (adjusted for height) remained stable. The Family Health Promotion program
      resulted in positive changes in cardiovascular risk factors and can be adapted to
      any clinical or health-promotion setting.

PMID- 7503117
TI  - Preventive cardiology and its potential influence on the early natural history of
      adult heart diseases: the Bogalusa Heart Study and the Heart Smart Program.
AB  - Observations from pediatric epidemiology studies over the past 20 years document
      that atherosclerosis and essential hypertension begin in childhood. Evidence of
      coronary artery disease and hypertensive cardiovascular renal disease is found
      and relates strongly to clinical cardiovascular risk factors. Obesity, especially
      central obesity, and hyperinsulinemia are commonly found, and these cluster with
      other risk factors. Lifestyles, such as poor eating behavior and tobacco usage,
      also begin early and influence cardiovascular risk. The implication from these
      pediatric observations is that intervention should begin early to prevent
      unhealthy lifestyles and encourage adoption of healthy behaviors. Where adult
      heart diseases pervade the major part of the United States population and other
      industrialized cultures, various epidemiologic strategies of prevention are
      needed. A high-risk, clinical approach can be applied to individuals with heart
      disease or to individuals with underlying risk factors and their families.
      Primary and secondary prevention are both important and should be implemented by
      primary care physicians. A population approach is also needed because of the
      widespread occurrence of heart disease. A public health approach to prevention
      can occur through health education and health promotion programs. Physicians
      should play a role in encouraging prevention for the general population. The
      future direction of Preventive Cardiology for our nation rests on educating
      children to adopt and maintain healthy lifestyles. The Bogalusa Heart Study has
      made a major contribution in providing the background information for that
      direction.

PMID- 7503118
TI  - Concept of bridging the gap from youth to adulthood.
AB  - Clinical atherosclerotic cardiovascular disease reaches substantial incidence
      beginning at age 45 years in men and age 55 years in women but has its onset in
      childhood. Lesions progress in relation to exposure to identified risk factors
      and, once initiated, tend to be self-perpetuating. Because predisposing factors
      are often initiated in childhood, interventions beginning early in life are
      optimal for prevention of adult disease. Even genetically predisposed people
      usually require an unfavorable lifestyle for the atherogenic trait to be
      expressed. No combination of risk factors entirely accounts for the increase in
      clinical atherosclerotic events with advancing age. This may be a reflection of
      longer exposure to risk factors or impaired ability to cope with them in advanced
      age. The declining risk factor risk ratios with advancing age may be a
      consequence of the selective early removal of those most susceptible from the
      population at risk. Risk of major cardiovascular events increases about 2.5-fold
      with each 10 years of age, even in people without major risk factors who are
      considered at low risk for atherosclerotic cardiovascular events. However, at any
      age vulnerability to cardiovascular events is strongly influenced by the burden
      of risk factors. Decreased risk ratios with advanced age are offset by a greater
      absolute risk. The female advantage over men erodes with age, with the menopause
      and with acquisition of an unfavorable lipid profile and glucose intolerance.

PMID- 7503119
TI  - Rationale to study the early natural history of heart disease: the Bogalusa Heart
      Study.
AB  - The Bogalusa Heart Study now establishes that precursors of adult cardiovascular
      diseases begin in childhood. The clearest evidence comes from autopsy studies
      that show coronary atherosclerotic lesions occur in early life and are strongly
      associated with very-low-density lipoprotein cholesterol, systolic and diastolic
      blood pressure, and obesity, and have an inverse relationship with high-density
      lipoprotein cholesterol. Observations of cardiovascular risk factors span a
      period of life from birth to 31 years of age, and longitudinal studies span a 15
      year period. Risk factor variables tend to persist over time, "track." Although
      tracking is best for height and weight, low-density lipoprotein cholesterol and
      serum total cholesterol track at a high order; blood pressure tends to track at a
      lower order. Obesity and body fatness have an adverse influence on risk factors
      in children, just as noted in adults, with central obesity becoming more obvious
      after puberty, and having a greater adverse effect on risk factors. The emergence
      of abnormal levels of risk factors by adult criteria begins to occur in young
      adults, and is not evident in childhood. Retrospective studies, interestingly,
      for obesity, higher blood pressure, and dyslipidemia reveal evidence of their
      presence already in childhood. These findings have strong implications for
      undertaking prevention in early life.

PMID- 7503120
TI  - An overview of the quantitative influence of several risk factors on progression
      of atherosclerosis in young people in the United States. Pathobiological
      Determinants of Atherosclerosis in Youth (PDAY) Research Group.
AB  - This overview of the National Institutes of Health-supported, multicenter,
      investigator-initiated study of the Pathobiological Determinants of
      Atherosclerosis in Youth (PDAY) is designed to summarize the plan, approaches,
      and the expanding contribution of this unique research program, which is now in
      its tenth year. It traces for the first time the development, the organization,
      and the function of the many new features and facets that are being used to yield
      needed information on the relationships between the classic risk factors and the
      topography, severity, and the cellular and chemical reactions that influence the
      development of the early raised plaques. It has also helped establish the factors
      that influence the progression of the four major types of intermediate raised
      lesions that grossly are all similar, well delineated fatty plaques. Most of the
      observations are quantitative. A few glimpses into the unique findings that have
      been published are presented.

PMID- 7503121
TI  - The early natural history of atherosclerosis and hypertension in the young:
      National Institutes of Health perspectives.
AB  - Atherosclerotic cardiovascular disease begins decades before its clinical
      manifestations first appear. Early detection may offer the best chance for
      prevention. The National Heart, Lung, and Blood Institute has sponsored several
      population studies that have described the development of cardiovascular disease
      risk factors and their relationship to the emergence of early atherosclerotic
      lesions. Clinical trials are underway testing interventions to lower risk factors
      in the young. Guidelines for clinicians have been promulgated. Advances in
      molecular biology and noninvasive imaging techniques will provide new
      opportunities to explore the interaction of genetic and environmental factors in
      the initiation of cardiovascular disease. In the future, individuals at high risk
      for progression of atherosclerosis may be identified earlier, when prevention
      will be more successful.

PMID- 7503122
TI  - Risk factors and atherosclerosis in youth autopsy findings of the Bogalusa Heart
      Study.
AB  - The Collaborative Pathology Study is one of the most impressive programs of the
      Bogalusa Heart Study. Attempts are made to obtain complete and uniform necropsy
      coverage of all decreased young people who may have been examined in the Bogalusa
      Heart Study. Since 1978, autopsy specimens have been collected from 190 deaths,
      representing 65% of all known deaths in the study age category. The relation of
      antemortem risk factors for cardiovascular disease to early atherosclerotic
      lesions in the aorta and coronary arteries was assessed in those individuals
      previously examined in the Bogalusa Heart Study (N = 59). Aortic fatty streaks
      were strongly related to both total and low-density lipoprotein (LDL) cholesterol
      (r = 0.62, P < 0.0001 for each association), and were inversely correlated with
      the ratio of high-density lipoprotein (HDL) cholesterol to LDL plus very-low
      density lipoprotein (VLDL) cholesterol (r = -0.29, P < 0.01). Coronary artery
      fatty streaks were associated with elevated total cholesterol, LDL cholesterol,
      VLDL cholesterol, and systolic blood pressure. Higher levels of LDL and VLDL
      cholesterol, triglycerides, systolic and diastolic blood pressure, and a lower
      ratio of HDL to LDL plus VLDL were found in those people with coronary artery
      fibrous plaques. Microscopy offered additional information about the
      characteristics of the aortic and coronary arterial intimal disease. Histologic
      observations have confirmed some of the relationships indicated with gross
      observations and show the complexity of this disease process. These findings
      emphasize the importance of an approach to preventive cardiology early in life.

PMID- 7503123
TI  - The role of the pediatrician in the promotion of cardiovascular health.
AB  - The subspecialist has been historically on the forefront of diagnosis and
      management of cardiovascular disease in our society. Recently, however, we have
      seen the focus shifting from high technology to include primary care and
      prevention. Cardiovascular risk evaluation has been identified as the thrust of
      the 1990s, and there is a reemergence of the generalist as a potential leader in
      cardiovascular care. It is now recognized that efforts early in life to promote
      cardiovascular health may have dramatic impact beyond the pediatric age. Five
      major areas are identified as targets for cardiovascular health promotion in
      childhood: obesity, cardiovascular fitness, hypertension, hypercholesterolemia,
      and smoking prevention. Pediatricians, as well as family physicians, must
      recognize their critical role in the promotion of cardiovascular health. The
      focus should not be limited to traditional childhood diseases but also to adult
      diseases that have their origins in childhood. Appreciation of the scientific
      findings generated by studies such as the Bogalusa Heart Study should influence
      the pediatrician in assuming a major role in prevention of adult heart and other
      chronic diseases.

PMID- 7503124
TI  - Continuing advances in hypertension: the Joint National Committee's fifth report.
AB  - This report focuses on the new features of the Joint National Committee's most
      recent report (JNC-5) on the detection, evaluation and treatment of hypertension.
      It highlights the new classification of hypertension based on stages of the
      disease, and the recent demonstration that primary prevention of hypertension is
      feasible and practicable, and it provides a rationale for its recommendations on
      the selection of initial therapy for the treatment of hypertension. The latter
      discussion also provides a reasoned response to certain related issues that have
      engendered controversy relating to these recommendations.

PMID- 7503125
TI  - Obesity studies in Bogalusa.
AB  - Obesity is a determinant of cardiovascular risk factors in childhood,
      adolescence, and adulthood. Since the inception of the Bogalusa Heart Study,
      various anthropometric measures of body size and mass have been obtained.
      Attention is given to identifying the distribution for various obesity measures,
      secular trends in obesity, clustering of obesity with other risk factors, and
      obesity during childhood as a predictor of risk factors during young adulthood.
      Race, gender, and age differences offer clues to etiology of future clinical
      disease and cardiovascular risk. Innovative programs are needed to alter the
      secular trend over the past 20 years toward increased obesity. General wellness
      must include a reduction in obesity.

PMID- 7503126
TI  - Childhood lipoprotein profiles and implications for adult coronary artery
      disease: the Bogalusa Heart Study.
AB  - Serum lipoproteins are important risk factor variables for coronary artery
      disease (CAD). Studies of a large population of young individuals show changes in
      lipoproteins in childhood are race- (black-white) and sex-specific and certain
      changes occur during growth phases. White boys show adverse changes in
      lipoprotein levels during sexual maturation that mark them at high risk for CAD.
      Further, low-density lipoprotein particles are relatively apolipoprotein B
      enriched in white children, especially boys, a characteristic associated with low
      levels of high-density lipoprotein cholesterol. The impact of apolipoprotein E
      genotype on serum lipoproteins seen in adults is already apparent in children,
      which may be helpful in identifying a high-risk group. Observations of child
      parent associations in terms of parental myocardial infarction and levels of
      lipoprotein variables in the offspring suggest that childhood profiles of
      lipoprotein (a), apolipoprotein A-I, and apolipoprotein B may be helpful as
      markers of future CAD. Clustering of increased levels of truncal fat, insulin,
      and blood pressure is often seen in young adults with an adverse lipoprotein
      profile. This clustering is related to subtle abnormalities in carbohydrate and
      lipid metabolism and obesity in childhood. The fact that lipoprotein levels
      persist from childhood to young adulthood underscores the importance of detection
      and management of dyslipidemia early in life.

PMID- 7503127
TI  - A perspective on obesity.

PMID- 7503128
TI  - The importance of body fat distribution in early life.
AB  - It is possible that many of the conflicting findings concerning obesity and
      cardiovascular disease may be the result of the heterogeneous nature of obesity,
      adn that only certain subgroups of the obese are at increased risk. Over the last
      several decades, much attention has focused on the distribution of body fat as an
      important characteristic in the metabolic and clinical alterations associated
      with obesity. Several studies have shown that a relative excess of adipose tissue
      in the upper body, abdominal region, or at various truncal sites is associated
      with an increased risk of disease; furthermore, these associations are
      independent of the general level of obesity. This article presents a brief
      historical overview of the idea of body fat distribution, the measurement
      techniques that have been used, and the complications associated with an adverse
      distribution of body fat distribution; particular emphasis is given to studies
      that have examined fat patterning in early life. Although most investigators
      recognize that body fat distribution is important in the development of
      cardiovascular disease, several questions remain.

PMID- 7503129
TI  - Does adult-onset diabetes mellitus begin in childhood?: the Bogalusa Heart Study.
AB  - Children and young adults (N = 52, age 7-31, average 15.3 years) from parents
      with or without a history of onset of diabetes mellitus after the age of 30 years
      were studied for anthropometric and metabolic parameters related to diabetes. An
      oral glucose tolerance test was performed and blood samples were collected
      fasting and 15, 30, and 60 minutes after a standard glucose load. Offspring of
      diabetic parents were significantly heavier and more obese, although not
      uniformly overweight. Blood pressure, fasting insulin, glucagon, and
      triglycerides were significantly higher in offspring of diabetic parents.
      Approximately one-half of the offspring and siblings of diabetic parents had 30
      minute blood glucose levels greater than 161 mg/dL, whereas none of the controls
      exceeded this level. These observations suggest abnormalities consistent with
      diabetes mellitus are already present in children and young adults, and may be
      detected by a response to glucose load.

PMID- 7503130
TI  - Trends in heart disease in the United States.
AB  - The twentieth century in the United States has witnessed a "heart disease
      epidemic" with a dramatic increase in ischemic heart disease (IHD) among men,
      particularly, beginning shortly after World War I. The epidemic reached its peak
      mortality among men in the 1960s and among women about two decades earlier.
      Highest mortality rates were observed in the Northeast at mid-century, but by
      1990 the highest rates occur in the Southeast. With improvements in survival
      during the past few decades, prevalence of IHD has been increasing in the
      population. Identification of risk factors for IHD through longitudinal
      epidemiologic studies has led to prevention programs that have improved the risk
      profile of the population.

PMID- 7503131
TI  - Perspectives of public health and prevention.
AB  - The average life expectancy at birth of Americans has increased 30 years since
      the turn of the century and is mostly attributable to public health measures.
      Although death rates for cardiovascular diseases have declined in the past two
      decades, cardiovascular diseases still cause more deaths in the United States
      than all other causes combined. The major etiologies of heart disease,
      atherosclerosis and hypertension, are associated with modifiable risk factors-
      high blood cholesterol, high blood pressure, cigarette smoking, diet, and
      inactivity. Social status and access to medical care are also important
      contributors. Consequently, the greatest potential for reducing heart disease
      mortality and morbidity rests with prevention and public health practice. Recent
      directions in health-care reform emphasize fiscal management, medical care, and
      clinical medicine, and not general health. This emphasis exacerbates policy and
      financing imbalances between preventive and curative medicine. Consequently, the
      concept of a health system needs to be designed more rationally to allocate
      resources that include prevention and health promotion. The Bogalusa Heart Study
      provides understanding of the early origin of cardiovascular problems and the
      environmental and lifestyle factors that contribute to development of adult heart
      disease. To apply this information, public health models of intervention, like
      the school Health Ahead/Heart Smart program, are needed to address heart disease
      in the population. Changes in the true determinants of poor health, such as
      environmental factors and unhealthy behaviors, are the directions for prevention
      and future improvement in quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503132
TI  - Racial differences in the pathogenesis of hypertension.
AB  - Hypertension occurs at an earlier age, is more prevalent, and is more often
      complicated by target organ damage in African-Americans than whites. Reasons for
      this increased severity of hypertension in African-Americans remain obscure.
      Based on studies recently completed in their laboratory, the authors propose that
      greater sympathetic reactivity to stress and a greater prevalence of NaCl
      sensitivity contribute to the earlier development of hypertension in African
      Americans. Using microneurography to record muscle sympathetic nervous system
      activity, it was found that normotensive blacks manifest greater increases in
      sympathetic activity to cold stress than normotensive whites. If true of other
      types of stressors, greater sympathetic reactivity would predispose blacks to the
      development of hypertension. Using a telemetry-based monitoring system, the
      authors recently reported that both spontaneously hypertensive rats and
      normotensive Wistar-Kyoto rats manifest acute sensitivity to high dietary NaCl
      ingestion, but that the Wistar-Kyoto rats are able to compensate, thereby
      avoiding sustained increases in blood pressure. Based on these animal studies, it
      is proposed that elevated nocturnal pressures observed in blacks by other
      investigators may reflect the greater prevalence of NaCl sensitivity in the black
      population. As in animal models of NaCl-sensitive hypertension, blacks may retain
      ingested NaCl, resulting in sustained increases in blood pressure.

PMID- 7503133
TI  - Development of risk factors for cardiovascular disease among women from
      adolescence to older ages.
AB  - The development of risk factors for young adults to older ages for women has been
      evaluated in several studies. The increase in risk factor levels is related to
      age, weight gain, and diet. The levels of risk factors are related to extent of
      atherosclerosis, even at relatively young ages. The prevention of increase in
      risk factors is of primary importance for the future reduction of morbidity and
      mortality due to cardiovascular disease.

PMID- 7503134
TI  - Extrarenal potassium adaptation: review of a concept.
AB  - Animals chronically fed a high-potassium diet may survive an acute potassium load
      which is lethal to animals fed a control diet. This 'potassium tolerance' is
      clearly related to an enhanced ability of the kidneys to excrete potassium.
      However, in their now classic studies, Alexander and Levinsky suggested that a
      nonrenal mechanism also contributes to this phenomenon. They showed that despite
      nephrectomy just prior to acute potassium loading, animals accustomed to a high
      potassium diet had a smaller increment in plasma potassium than did controls. As
      a result of this work, it is now widely believed that chronic exposure to large
      amounts of potassium somehow directly enhances cellular potassium uptake, a
      process referred to as extrarenal potassium adaptation. However, it is important
      to note that in these studies, the animals were fasted prior to nephrectomy. We
      have shown that when potassium is withdrawn from potassium-adapted animals, high
      rates of potassium excretion persist and eventually result in the development of
      paradoxical potassium depletion. We believe that it is this potassium depletion
      which accounts for the enhancement of cellular potassium uptake sometimes seen in
      potassium-adapted animals. Indeed, extrarenal potassium adaptation can only be
      demonstrated after a prolonged period of dietary potassium withdrawal has
      provided the opportunity for potassium depletion to occur. Furthermore, there is
      actually little evidence that chronic potassium feeding directly enhances the
      cellular uptake of an acute potassium load. We conclude that extrarenal potassium
      adaption is a time-honored concept which, for practical purposes, does not exist.

PMID- 7503135
TI  - Anti-Nform antibody in hemodialysis patients.
AB  - The anti-Nform antibody is produced by dialysis patients following reuse of
      dialyzers sterilized with formaldehyde and it has been implicated as a cause of
      hemolytic anemia. Formaldehyde is one of the common disinfectants used for
      reprocessing capillary hemodialyzers. The safety of formaldehyde and the clinical
      significance of anti-Nform antibody need further evaluation. Amongst 45 patients
      practising dialyzer reuse, anti-Nform antibody was detected in 5 (11.1%), but not
      amongst 111 patients not reusing their dialyzer (p < 0.005). The presence of anti
      Nform was not related to the sex, or duration of dialysis with positive anti
      Nform antibody. Direct Coombs' test was positive amongst 80% of all tested
      patients with anti-Nform antibody, and in 38% of patients reusing dialyzers but
      without anti-Nform antibody. No tests of hemolysis (including direct Coombs'
      test) discriminated between anti-Nform antibody-positive and -negative patients,
      nor between anti-Nform antibody patients with and without overt hemolysis. The
      best diagnostic test for hemolysis in anti-Nform antibody-positive patients was
      hematocrit rise after cessation of dialyzer reuse. It appears that despite the
      induction of anti-Nform antibody, hemolysis is rarely a serious consequence of
      dialyzer reuse.

PMID- 7503136
TI  - Pathobiology and functional status of long-term hemodialysis patients.
AB  - There may be cumulative 'metabolic scars' after a decade or more of long-term
      hemodialysis. We studied 39 patients who have been on maintenance hemodialysis
      for 10-24 years to determine their functional status and pathobiology. The 39
      long-term (> or = 10 years) patients were compared with a control cohort of 37
      age-, gender-, race-, and renal-diagnosis-matched patients on hemodialysis for <
      or = 3 years. The functional status was measured using a modified Karnofsky
      scale, and the employment status was noted as well. Details of hospitalizations
      and intercurrent infections requiring outpatient oral or intravenous antibiotic
      therapy during the preceding year were obtained. Comorbid medical conditions were
      documented, and basic laboratory tests were performed. The mean age of the long
      term patients was 51.8 +/- (SE) 1.9 years, and the mean age of the control group
      was 51.5 +/- 2.4 years (p = 0.92). Three times weekly hemodialysis prescriptions
      were similar in both groups (long-term: 3.5 +/- 0.02 h, control: 3.4 +/- 0.02 h;
      p = 0.27). The mean modified Karnofsky scores were equivalent in both groups. The
      rate of hospitalization during the preceding year was higher among the long-term
      patients (0.92 +/- 0.19/patient year) than in the control patients (0.51 +/-
      0.15/patient year; p = 0.09). The long-term patients had more intercurrent
      infections (1.23 +/- 0.21) than the controls (0.68 +/- 0.16; p = 0.04). (ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7503137
TI  - Clinical and immune aspects of idiopathic acute tubulointerstitial nephritis and
      uveitis syndrome.
AB  - Five patients with idiopathic interstitial nephritis and uveitis without bone
      marrow granulomas were followed-up for 1 year. Ophthalmological examination
      revealed bilateral anterior uveitis. Light microscopy of the renal tissue
      revealed predominant lymphocyte infiltration of the interstitium.
      Immunohistochemical analysis revealed a clear predominance of memory T
      lymphocytes (CD45RO+) in the interstitial and tubular infiltration. HLA typing,
      and immunophenotypic studies of peripheral blood mononuclear cells including
      absolute lymphocyte and monocyte counts were assessed. The patients' peripheral T
      cell subpopulation did not significantly differ from control studies. With
      steroid treatment maintained during a period of 6-9 months renal function and
      uveitis responded dramatically in all patients. After 1-year follow-up, only 1
      patient showed a relapse of uveitis, but there was complete clinical recovery of
      the nephritis in all 5 patients. The aim of this study was to describe the 1-year
      follow-up of 5 new cases of acute tubulointerstitial nephritis and uveitis
      syndrome, and assess some aspects of their cellular immunity.

PMID- 7503138
TI  - Cell surface receptor modulation on monocytes and granulocytes during clinical
      and experimental hemodialysis.
AB  - We studied the modulation of cell surface receptors related to cell adhesion (L
      selectin and Mac-1) on monocytes and granulocytes during clinical (7 patients
      treated with cuprophan, Cu, and polysulfone, PS, membranes, n = 14) and
      experimental Cu and PS hemodialysis (n = 14). The objective was to compare cell
      surface receptor modulation in vivo when large subpopulations of cells are
      withdrawn from the circulating pool with the experimental model when cells are
      not sequestrated. The expression of Mac-1 and L-selectin on monocytes increased
      during clinical Cu dialysis (p = 0.024 and p = 0.0096, respectively) but remained
      stable during PS dialysis. On granulocytes, an inverse receptor modulation of Mac
      1 and L-selectin was observed during clinical Cu dialysis but not during PS
      dialysis. Mac-1 was significantly higher and L-selectin lower on granulocytes
      after 15 min of clinical Cu as compared to PS dialysis (p = 0.001 and p = 0.0093,
      respectively). During experimental Cu dialysis, Mac-1 expression increased and L
      selectin decreased markedly and continuously on both monocytes and granulocytes.
      The L-selectin/Mac-1 ratio on monocytes and granulocytes may be used as an index
      of the ability of leukocytes to adhere and to be recruited to an inflammatory
      focus. This ratio was significantly lower during clinical Cu as compared to PS
      dialysis (p = 0.0008 and p = 0.0015 respectively) indicating that the recruitment
      of leukocytes to infection foci may be precluded in patients on Cu membranes.
      Both monocytes and granulocytes showed significantly lower L-selectin/Mac-1 ratio
      during and after experimental Cu as compared to PS dialysis.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7503139
TI  - The effect of peroral calcitriol in small doses on mild secondary
      hyperparathyroidism in patients on hemodialysis.
AB  - Our prospective 1-year study comprises 93 patients of both sexes, various ages
      and various dialysis duration. Among them, 31 patients with a concentration of Ca
      in blood under 2.7 mmol/l, a concentration of P under 1.8 mmol/l and a
      concentration of PTHi over 65 pg/ml (group 0) received calcitriol 0.25
      microgramx418p4The control group consisted of patients not receiving calcitriol
      and having normal Ca and P metabolism (group 1). The rest of the patients had a
      concentration of P over 1.8 mmol/l and could not be given calcitriol. A
      comparison of the dynamics of average plasmic concentrations of Ca, P, AP, PTHi
      and X-ray changes in group 0 and 1 at the beginning of the investigation and 1
      year later was carried out. At the termination of the 1-year treatment, when
      compared to the initial state, a statistically significant increase in the
      concentration of Ca (p < 0.005) and in the concentration of P (p < 0.005) was
      noted in group 0. The average concentration of PTHi decreased to the desired
      level, the X-ray changes characteristic of secondary hyperparathyroidism
      progressed more slowly in group 0.

PMID- 7503140
TI  - Hepatitis C associated glomerulonephritis.
AB  - To determine the prevalence and type of glomerulonephritis (GN) associated with
      hepatitis C virus (HCV) cirrhosis, we prospectively evaluated 28 consecutive
      Saudi patients with HCV cirrhosis for liver transplantation. Six patients (21%)
      underwent kidney biopsies for proteinuria, unexplained elevated serum creatinine
      or both. All 6 had GN, 4 had membranoproliferative, one focal segmental and one
      membranous GN. Immunologic and electron microscopic studies demonstrated immune
      complex deposition in the glomeruli. Two patients with significant proteinuria
      were treated with interferon alpha for 3 months with improvement in kidney and
      liver function. To our knowledge, this is the first report of focal segmental GN
      associated with HCV. This high prevalence of HCV associated GN is alarming and
      warrants further studies in cirrhotic and noncirrhotic patients, particularly as
      an indication for therapeutic intervention.

PMID- 7503141
TI  - Interstitial myofibroblasts in experimental renal infection and scarring.
AB  - We have examined the temporal and spatial distribution of myofibroblast-like
      cells, a phenotype with fibroblast and smooth muscle features, in an experimental
      model of renal infection. Escherichia coli organisms (10(5)) were inoculated
      directly into the renal cortex of Sprague-Dawley rats weighing 270 g. Saline was
      substituted in a control group. The animals were sacrificed at five time points
      up to day 24 (E. coli n = 8, controls n = 3 each interval). Myofibroblasts were
      identified by morphology and immunohistochemistry for alpha smooth muscle actin
      (alpha-SMA) and compared with staining for monocytes (ED-1), collagen III, and
      bromodeoxyuridine incorporation. Histological changes included a focal lesion in
      E. coli infected animals. Interstitial alpha-SMA staining was confined to spindle
      shaped cells resembling myofibroblasts. The percent fractional area of alpha-SMA
      staining in the lesion increased from 0.12 +/- 0.09 at day 1 to 20.0 +/- 7.1 at
      day 3 (p < 0.005), decreasing progressively to 2.0 +/- 2.6 by day 24. This
      paralleled bromodeoxyuridine incorporation in myofibroblasts: 0.4 +/- 0.5
      cells/0.25 mm2 at day 1, 105.0 +/- 36.3 at day 3, and 2.6 +/- 2.2 cells/0.25 mm2
      at day 24. ED-1-positive cells increased from 374 +/- 200/0.25 mm2 at day 1 to
      894 +/- 88 at day 3 (p < 0.01), declining to 230 +/- 108/0.25 mm2 by day 24.
      Intracellular collagen III and alpha-SMA stainings were colocalized at day 3. The
      fractional area of collagen III increased by day 24 (p < 0.05). In conclusion,
      myofibroblasts accumulate transiently during renal interstitial fibrosis and are
      derived at least in part from local proliferation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7503142
TI  - Effects of urodilatin and diltiazem on renal function in ischemic acute renal
      failure in the rat.
AB  - In humans as well as in experimental models the hallmark of ischemic acute renal
      failure (ARF) is a profound diminution in glomerular filtration rate (GFR) and
      renal blood flow. Both calcium antagonists and a-ANP have been reported to exert
      beneficial effects in ischemic ARF. No data, however, exist about combined
      administration of the natriuretic peptide urodilatin and calcium channel
      blockers. We therefore investigated the effects of urodilatin (URO, 40
      micrograms/kg/h, i.v.) and diltiazem (DIL, 300 micrograms/kg/h, i.v.) in the rat
      given immediately after clamping of both renal arteries for 40 min. Compared to
      controls (0.07 +/- 0.01) depressed GFR (ml/min/100 g) was clearly elevated with
      URO (0.16 +/- 0.03), DIL (0.13 +/- 0.03) and URO + DIL (0.14 +/- 0.02) after the
      ischemic lesion. After cessation of drug delivery the beneficial effects were
      blunted in the URO group, in contrast to the DIL and URO + DIL group, where GFR
      was significantly elevated compared to controls even 3 h after starting
      reperfusion. Besides that also urine flow, sodium excretion and blood pressure
      were examined. In conclusion both URO and DIL exert beneficial effects in
      ischemic ARF in the rat while infused. In contrast to URO DIL showed prolonged
      beneficial effects even after cessation of drug delivery. An additional effect of
      both drugs could not be observed.

PMID- 7503143
TI  - Acute progressive and extensive metastatic calcifications in a nephrotic patient
      following chronic hemodialysis.
AB  - We report on a 46-year-old female patient with a 5-year history of refractory
      nephrotic syndrome who rapidly developed extensive metastatic calcifications in
      lung, bone, blood vessels, skin, uterus and other soft tissues following
      maintenance hemodialysis. She was admitted for controlling anasarca. On
      admission, she suffered from severe nephrotic syndrome and chronic renal failure,
      showing 1.3 g/dl of serum albumin and 4.6 mg/dl of serum creatinine. She received
      bicarbonate dialysis combined with extracorporeal ultrafiltration to control
      anasarca. Following hemodialysis, she was treated with alfacalcidol and an
      increasing dose of calcium carbonate. Although anasarca was controlled, her
      nephrotic state remained unchanged. After 3 months of dialysis, roentgenograms of
      the body disclosed multiple metastatic calcifications. At this time, though the
      calcium-phosphorous product in serum was almost normal, the free calcium index
      was confirmed to have been high for 4 weeks. We considered that administration of
      calcium carbonate and alfacalcidol as well as an influx of free calcium from a
      dialysate resulted in increased serum ionized calcium which may be unable to be
      bound to serum protein because of lack of total protein, leading to ectopic
      deposition of calcium and phosphate. Our findings suggested that intensive care
      is needed to prevent metastatic calcification when uremic patients with severe
      nephrosis are treated with bicarbonate hemodialysis.

PMID- 7503144
TI  - Unreliability of the abdominal fat pad biopsy in the evaluation of nephrosis:
      report of 3 consecutive cases.
AB  - In the workup of unexplained nephrotic syndrome in the elderly patient, renal
      biopsy has shown amyloidosis to be the cause in 15-30% of the cases. Most of the
      cases of amyloidosis are primary and are, therefore, treatable with alkylating
      agents, albeit at a high level of toxicity. Abdominal fad pad biopsy has been
      suggested as a minimally invasive, low-cost method for diagnosing amyloidosis
      that is 100% specific. We report our experience with 3 consecutive cases of fat
      pad biopsy in the workup of unexplained nephrosis in the elderly patient:
      including the first false positive reported with respect to nephrotic renal
      disease, a false negative, and a true positive. We feel that in an elderly
      patient with unexplained nephrosis though the abdominal fat pad biopsy may be
      helpful, the patient should not be committed to a regimen with potentially very
      high toxicity on the basis of a positive fat pad biopsy alone. We recommend that
      the more invasive renal biopsy be performed should therapy with alkylating agents
      be contemplated.

PMID- 7503145
TI  - Glomerulonephritis associated with permanent pacemaker endocarditis.
AB  - Two patients with permanent transvenous cardiac pacemakers were seen with a
      history of pyrexia of unknown origin and renal failure. After extensive
      investigation both were found to have pacemaker endocarditis. A renal biopsy of
      one patient revealed changes characteristic of glomerulonephritis associated with
      this condition. Both patients underwent thoracotomy for open removal of their
      pacemaker and appropriate antibiotic treatment. One patient made a good recovery
      of renal function. Unfortunately the second patient died. These reports emphasize
      the need for vigilance for these two uncommon complications and the difficulty in
      their diagnosis.

PMID- 7503146
TI  - Minimal-change nephrotic syndrome associated with systemic lupus erythematosus.
AB  - A case of systemic lupus erythematosus (SLE) associated with minimal-change
      nephrotic syndrome (MCNS) is described. A 41-year-old woman with SLE presented
      with symptoms of nephrotic syndrome. Renal biopsy revealed minor glomerular
      abnormalities without the deposition of immune complexes. The initial heavy
      proteinuria promptly decreased after the prednisolone dosage was increased and
      disappeared 4 weeks later. The patient had a relapse of nephrotic syndrome
      without exacerbation of immunoserological reactions when the prednisolone dose
      was subsequently decreased. Remission was achieved 5 days after
      methylprednisolone pulse therapy. T cell dysfunction, which is present both in
      SLE and MCNS, might have triggered MCNS during the course of SLE.

PMID- 7503147
TI  - Familial focal glomerulosclerosis: a genetic linkage to the HLA locus?
AB  - The aetiology and pathogenesis of focal glomerulosclerosis is poorly understood
      and many conflicting reports suggest HLA locus associations in both familial and
      non-familial glomerulosclerosis. We report a family in which 4 of 5 sisters
      developed proteinuria, 2 with hypertension and 1 progressing to end-stage renal
      failure (index case). Three underwent renal biopsy which displayed characteristic
      features of focal glomerulosclerosis and all shared the HLA alleles HLA-A1, B8,
      DR3, DR7. The index case received two cadaveric renal transplants from HLA-A1,
      B8, DR3 donors and developed chronic rejection with no histological evidence of
      recurrent glomerulonephritis in either kidney. The frequency of this haplotype in
      the Australian dialysis and transplant population with focal glomerulosclerosis
      was compared to that seen in the general Australian Caucasian population and was
      not significantly different suggesting that the presence of the HLA alleles HLA
      A1, B8, DR3, DR7 may increase the predisposition to familial glomerulosclerosis
      but additional factors are required for disease development and progression.

PMID- 7503148
TI  - Plasmapheresis maintained renal function in an allograft with recurrent
      membranoproliferative glomerulonephritis type I.
AB  - Six months posttransplant, a 38-year-old woman developed acute renal failure due
      to recurrent idiopathic membranoproliferative glomerulonephritis (MPGN) type I.
      MPGN was associated with an elevated rheumatoid factor and IgM deposition in the
      mesangium. Plasmapheresis with albumin replacement improved and maintained renal
      function for over a year while cytotoxic agents were administered in an attempt
      to control the glomerulonephritis. The patient currently has a functional renal
      allograft 2 years posttransplant.

PMID- 7503149
TI  - Pseudohyperkalemia in extreme leukocytosis.
AB  - Spurious elevation of blood K levels is a well known occurrence in patients with
      extreme leukocytosis. A common explanation is the in vitro release of K from
      leukocytes undergoing lysis during the clotting process. Since in clinical
      practice blood electrolytes are now being evaluated in plasma or whole
      heparinized blood rather than in serum, this source of error should almost have
      disappeared. Another mechanism may be prolonged storage of blood at room
      temperature or in the cold before performing the test, most likely since
      unphysiological conditions and/or shortage of metabolic fuels may impair Na/K
      ATPase activity in leukocytes, ensuing in K release from these cells. For these
      reasons, it is commonly advised that patients with extreme leukocytosis should
      have K levels determined on plasma samples that are separated promptly from the
      cellular elements. We have recently observed a case of pseudohyperkalemia in a
      patient with chronic lymphocytic leukemia which was unrelated to both of these
      mechanisms, and was instead related to a common mode of drawing blood, i.e. with
      vacuum tubes.

PMID- 7503150
TI  - Votive offerings of the kidney.

PMID- 7503151
TI  - Negotiating AIDS drug assistance programs.

PMID- 7503152
TI  - Lessons from success.

PMID- 7503153
TI  - Why withhold analgesia in the emergency department?

PMID- 7503154
TI  - Assessing pain in neonates.

PMID- 7503155
TI  - Overlooked drug effect.

PMID- 7503156
TI  - Recruiters' new role.

PMID- 7503157
TI  - Breaking through to the adolescent patient.

PMID- 7503158
TI  - Emergency! Meningococcal meningitis.

PMID- 7503159
TI  - AV blocks: are you up to date?

PMID- 7503160
TI  - Clinical snapshot. Intermittent claudication.

PMID- 7503161
TI  - Technology scorecard: what's right for you and your unit.

PMID- 7503162
TI  - 'I'd rather die than live this way'.

PMID- 7503163
TI  - Closing the research-practice gap.

PMID- 7503165
TI  - All history is written backwards.

PMID- 7503164
TI  - Home care. Motivating Beth.

PMID- 7503166
TI  - A hug for the holiday.

PMID- 7503168
TI  - Indications for examination of spontaneous abortion specimens: a reassessment.
AB  - The clinical evaluation of recurrent pregnancy loss is assessed in light of
      recent technical advances in trophoblast culture, ultrasonography, and chromosome
      analysis. With an algorithm based on karyotype results, cost-benefit calculations
      confirm that an average savings of $1099.47 per patient could be achieved if a
      policy of karyotype analysis of recurrent abortion specimens was emphasized. It
      is estimated that a specific chromosomal cause could be identified in 45% to 70%
      of such cases. A more concerted effort should be made to culture trophoblast
      tissue from recurrent pregnancy losses; such a policy would result in both
      emotional and financial rewards.

PMID- 7503167
TI  - Determinants of the optimal time in gestation to initiate antenatal fetal
      testing: a decision-analytic approach.
AB  - To identify the most important determinants of the optimal timing for the
      initiation of antenatal fetal testing in a high-risk pregnancy (such as insulin
      dependent diabetes mellitus), we performed a decision analysis based on a Markov
      model. The model incorporated several components: test sensitivity and
      specificity and week-specific probability estimates for fetal death, delivery,
      and neonatal morbidity and mortality. The analysis demonstrated that the optimal
      time in gestation to begin testing (from the combined standpoint of both
      maximizing neonatal survival and minimizing fetal death) was highly dependent on
      test specificity, the cumulative risk of fetal death (and its distribution
      throughout gestation), and the week-specific probabilities of neonatal death. For
      example, even with the increased risk of fetal death associated with insulin
      dependent diabetes, very high test specificity (> 99%) is required to recommend
      testing before 30 weeks. If tests of lower specificity (higher false-positive
      rates) are used, neonatal deaths will increase and will not be offset by a
      corresponding decrease in fetal deaths. By performing sensitivity analyses, we
      demonstrated the effect and relative importance of the model components for
      determining the optimal gestational age to initiate fetal testing.

PMID- 7503169
TI  - Fetal acoustic stimulation, an adjunct to external cephalic version: a blinded,
      randomized crossover study.
AB  - OBJECTIVE: Our purpose was to determine whether fetal acoustic stimulation can
      improve the chance of successful external cephalic version in patients at 36 to
      38 weeks' gestation with fetal midline spine position. STUDY DESIGN: A
      randomized, blinded crossover trial was performed. In this "N of 1" study, the
      patient served as her own control. RESULTS: Twenty-six patients were enrolled in
      the study, and three were excluded due to engagement of the fetal breech. In the
      initial trial with fetal acoustic stimulation to the maternal abdomen, 12 of 12
      (100%) changed position to spine lateral and 11 of 12 (92%) were successfully
      verted. In the control group (fetal acoustic stimulation to nurse's arm), none of
      11 (0%) changed position to spine lateral and one of 11 (9%) were successfully
      verted (p < 0.0001). In the crossover trial eight of 10 (80%) of the original
      placebo (control) patients were successfully verted after fetal acoustic
      stimulation to the maternal abdomen and none of 1 (0%) from the original
      treatment group were successfully verted after placebo fetal acoustic stimulation
      (p < 0.0001). Combined data from the original and crossover trials indicates 19
      of 22 (86%) successful versions after fetal acoustic stimulation to maternal
      abdomen compared with one of 12 (8%) that had successful external cephalic
      version after placebo fetal acoustic stimulation. CONCLUSION: Fetal acoustic
      stimulation shifts fetal position to spine lateral, which increases successful
      version of fetuses with midline fetal spine presentations.

PMID- 7503171
TI  - Prospective determination of chorionicity, amnionicity, and zygosity in twin
      gestations.
AB  - OBJECTIVE: Our purpose was to determine the predictive accuracy of a composite
      ultrasonographic evaluation for chorionicity, amnionicity, and zygosity in a
      consecutive series of twins. STUDY DESIGN: One hundred ten consecutive twins were
      seen for ultrasonography beginning January 1992. Chorionicity, amnionicity, and,
      zygosity were prospectively assessed with a composite of ultrasonographic
      findings (placental number, fetal sex, membrane thickness, and "twin peak" sign).
      Clinical and pathologic confirmation of chorionicity, amnionicity, and zygosity
      was available on 100 of these twins. RESULTS: The 100 twins had 3.6 +/- 1.6
      ultrasonographic scans each (mean +/- SD) with the first performed at 22.6 +/-
      6.9 weeks. Chorionicity, amnionicity, and zygosity were each predicted with > or
      = 91% sensitivity and specificity. In 35 (35%) cases zygosity could not be
      determined by either ultrasonographic or clinical or pathologic assessment at
      delivery. CONCLUSION: Chorionicity, amnionicity, and zygosity have important
      implications for antepartum management and prognosis of twins. By use of a
      composite of ultrasonographic findings, chorionicity, amnionicity, and zygosity
      were predicted with excellent reliability when they were prospectively tested in
      a heterogeneous consecutive series of twins.

PMID- 7503170
TI  - Fetal acoustic stimulation test: stimulus features of three artificial larynges
      recorded in sheep.
AB  - OBJECTIVE: The purpose of the current study was to evaluate the characteristics
      of vibroacoustic devices used for fetal stimulation. STUDY DESIGN: Intrauterine
      sound pressure levels over a frequency range of 40 to 5000 Hz were measured with
      hydrophones in anesthetized sheep. Stimulators included the AT&T (Martinsburg,
      W.V.) and Servox (Hearing Instruments, Piscataway, N.J.) artificial larynges, the
      Corometrics fetal acoustic stimulator (Wallingford, Conn.) and electric
      toothbrush. RESULTS: Intrauterine spectral patterns resulting from stimulation
      with the AT&T, Servox, and Corometrics devices were characterized by numerous
      high-level overtones above a fundamental frequency between 97 and 163 Hz.
      Fundamental frequencies recorded during toothbrush stimulation were 22 to 24 Hz
      with reduced but identifiable overtones up to 250 Hz. CONCLUSIONS: Fetal
      vibroacoustic stimulators that operate on the principle of the electronic
      artificial larynx produce very similar intrauterine sound pressure levels.

PMID- 7503172
TI  - Nucleated red blood cells: a marker for fetal asphyxia?
AB  - OBJECTIVE: Our purpose was to determine whether a relationship exists between the
      presence of nucleated red blood cells, hypoxic ischemic encephalopathy, and long
      term neonatal neurologic impairment. STUDY DESIGN: Nucleated red blood cell data
      from 46 singleton term neurologically impaired neonates were compared with cord
      blood nucleated red blood cells of 83 term nonasphyxiated newborns. The
      neurologically impaired neonates group was also separated as follows:
      nonreactive, nonreactive fetal heart rate from admission to delivery;
      tachycardia, reactive fetal heart rate on admission followed by tachycardia with
      decelerations; rupture, uterine rupture. The first and highest nucleated red
      blood cells value and the time to nucleated red blood cells disappearance were
      assessed. RESULTS: The neurologically impaired neonates group exhibited a
      significantly higher number of nucleated red blood cells per 100 white blood
      cells (34.5 +/- 68) than did the control group (3.4 +/- 3.0) (p < 0.00001). When
      the neurologically impaired neonates are separated as to the basis for the
      neurologic impairment, distinct nucleated red blood cell patterns were observed.
      Overall, the nonreactive group exhibited the highest mean nucleated red blood
      cell (51.4 +/- 87.5) count and the longest clearance times (236 +/- 166 hours).
      CONCLUSION: In this limited population, nucleated red blood cell data appear to
      aid in identifying the presence of fetal asphyxia. When asphyxia was present,
      distinct nucleated red blood cells patterns were identified that were in keeping
      with the observed basis for the fetal injury. In general, the closer the birth
      was to the asphyxial event, the lower was the number of nucleated red blood
      cells. Thus our data suggest that cord blood nucleated red blood cells could
      assist in the timing of fetal neurologic injury.

PMID- 7503173
TI  - Successful in utero therapy of fetal heart block.
AB  - OBJECTIVE: Congenital complete heart block is associated with maternal
      autoantibodies to Ro and La proteins, which injure the fetal cardiac conduction
      system. We administered dexamethasone to the mothers of five fetuses with heart
      block caused by maternal antibodies. STUDY DESIGN: We diagnosed five cases of
      fetal heart block at 20 to 23 weeks and treated all mothers with dexamethasone 4
      mg orally each day for the remainder of the pregnancy. All patients were positive
      for anti-SS-A (anti-Ro) and/or anti-SS-B (anti-La) antibodies. RESULTS: Four
      patients had complete heart block, and one had second-degree block. In two
      patients (one with complete heart block, one with second-degree heart block) the
      degree of block lessened with treatment. Hydrops in three complete heart block
      patients resolved after treatment. Maternal antibody levels did not change.
      Matched maternal and cord samples at delivery showed similar antibody levels.
      CONCLUSIONS: Complete heart block can respond to transplacental glucocorticoid
      therapy with improved cardiac conduction. Because there may be a concurrent
      myocarditis, treatment in utero may also improve cardiac contractility, leading
      to the observed rapid resolution of hydrops. Treatment with steroids that cross
      the placenta should be considered for newly diagnosed cases of complete heart
      block with positive antibody screens.

PMID- 7503175
TI  - Detection of hepatitis C virus antibodies and specific hepatitis C virus
      ribonucleic acid sequences in cord bloods from a heterogeneous prenatal
      population.
AB  - OBJECTIVE: Our aim was to quantify the prevalence of at-risk pregnancies for
      maternal-fetal hepatitis C virus transmission in a heterogeneous prenatal
      population by detection of both hepatitis C virus-specific antibody and hepatitis
      C virus ribonucleic acid sequences in cord bloods from their deliveries. STUDY
      DESIGN: An anonymous serosurvey of 1432 consecutive umbilical cord blood samples
      were analyzed for hepatitis C virus antibodies with a second-generation enzyme
      immunoassay with all hepatitis C virus antibody-positive samples batched and
      analyzed for both human immunodeficiency virus antibodies and hepatitis C virus
      ribonucleic acid sequences by polymerase chain reaction. RESULTS: Forty-seven of
      the samples (3.2%) were positive for hepatitis C virus antibodies; seropositivity
      rates differed significantly by socioeconomic status but not by race.
      Significantly more of the antibody-positive women underwent cesarean section for
      delivery (31.9% vs 21.9%, p = 0.03). Three (6.4%) hepatitis C virus antibody
      positive samples were also human immunodeficiency virus-antibody positive,
      whereas nine (19.1%) were hepatitis C virus ribonucleic acid positive.
      CONCLUSION: As many as 19% of hepatitis C virus antibody-positive women in this
      study also had hepatitis C virus ribonucleic acid isolated from their delivery
      cord blood samples, which may indicate an increased risk of vertical hepatitis C
      virus transmission in those pregnancies. Hepatitis C virus-specific antibody and
      ribonucleic acid detection may also be markers for other pregnancy complications
      that result in higher rates of cesarean section for these women.

PMID- 7503174
TI  - The effect of aspirin and indomethacin on prostacyclin and thromboxane production
      by placental tissue incubated with immunoglobulin G fractions from patients with
      lupus anticoagulant.
AB  - OBJECTIVE: We investigated the hypothesis that nonsteroidal antiinflammatory
      agents can influence the abnormal prostanoid production associated with
      antiphospholipid antibodies. We specifically assessed whether aspirin or
      indomethacin could eliminate the increased placental thromboxane production
      previously observed with immunoglobulin G fractions from patients with lupus
      anticoagulant without adversely affecting prostacyclin production. STUDY DESIGN:
      Immunoglobulin G fractions were prepared from the plasma of eight nonpregnant
      patients with antiphospholipid antibody syndrome and demonstrable lupus
      anticoagulant. Samples from each patient were then placed in incubation wells
      containing explants from normal term pregnancies and 10(-4) mol/L aspirin, 10(-7)
      mol/L indomethacin, or no added drug. Aliquots were removed at intervals up to 48
      hours of incubation and assessed for placental prostacyclin and thromboxane
      production by radioimmunoassay of the stable metabolites prostaglandin F1 alpha
      and thromboxane B2. RESULTS: The addition of aspirin to wells containing
      immunoglobulin G from patients with lupus anticoagulant was associated with a
      significant decrease in thromboxane production compared with wells without added
      drug, but prostacyclin production was unaffected. In contrast, the addition of
      indomethacin also decreased thromboxane production significantly, but
      prostacyclin production was also diminished, so the ratio of thromboxane to
      prostacyclin was unaffected. CONCLUSION: These results support a role for the use
      of aspirin for antiphospholipid antibody-related pregnancy loss through a
      mechanism similar to that postulated for preeclampsia, namely, selective
      inhibition of thromboxane production.

PMID- 7503177
TI  - Plasma and placental calcitonin gene-related peptide in pregnancies complicated
      by severe preeclampsia.
AB  - OBJECTIVE: Our purpose was to determine the concentration of calcitonin gene
      related peptide, a potent vasodilator, in maternal plasma, fetal plasma, and
      placental tissue from pregnancies complicated by severe preeclampsia. STUDY
      DESIGN: The following groups were studied: severe preeclampsia (group 1, n = 21),
      normal pregnancies matched for mode of delivery (group 2, n = 21), and
      nonpregnant women (group 3, n = 17). Maternal venous blood samples were drawn
      before labor, and fetal venous samples were drawn from the chorionic plate
      immediately after delivery. Calcitonin gene-related peptide was also quantified
      in placental tissue samples from 15 patients in group 1 and 15 patients in group
      2. Calcitonin gene-related peptide was measured with a sensitive and specific
      radioimmunoassay. RESULTS: No differences were found between maternal plasma
      calcitonin gene-related peptide concentrations in groups 1 and 2 (29.8 +/- 4.2
      and 30.4 +/- 4.3 pmol/L, respectively). Both had levels similar to those in group
      3 (28.5 +/- 5.4 pmol/L). Maternal plasma concentrations in the preeclamptic group
      were unchanged 3 days post partum (29.1 +/- 3.6 pmol/L). Fetal plasma calcitonin
      gene-related peptide concentrations were similar in groups 1 and 2 (30.2 +/- 3.9
      and 32.2 +/- 8.8 pmol/L, respectively). A significant correlation was found
      between maternal and fetal calcitonin gene-related peptide concentrations (r =
      0.43, p < 0.01). Like plasma levels, calcitonin gene-related peptide levels in
      the supernatants of placental extracts were not different in preeclamptic and
      normal pregnancies (108.0 +/- 70.4 and 100.9 +/- 56.1 fmol/gm, respectively).
      CONCLUSION: On the basis of plasma and placental concentrations, calcitonin gene
      related peptide does not seem to play an important role in the pathophysiologic
      mechanisms of preeclampsia.

PMID- 7503176
TI  - Fetal lung maturation in congenital diaphragmatic hernia.
AB  - OBJECTIVE: Our purpose was to determine whether congenital diaphragmatic hernia
      is associated with abnormalities of fetal lung maturation. STUDY DESIGN: We
      measured surfactant protein A and saturated phosphatidylcholine in amniotic fluid
      from 19 pregnancies with a prenatal diagnosis of congenital diaphragmatic hernia
      (gestational age 16 to 40 weeks) and 48 control pregnancies (gestational age 16
      to 39 weeks). Results were compared by analysis of covariance. RESULTS: Beyond 34
      weeks of gestation there was a progressive rise in amniotic fluid surfactant
      protein A and saturated phosphatidylcholine in control pregnancies, whereas in
      most fetuses with prenatal diagnosis of congenital diaphragmatic hernia these
      values remained low (p < 0.01). Amniotic fluid surfactant protein A was lower in
      fetuses with congenital diaphragmatic hernia who died or required extracorporeal
      membrane oxygenation than in survivors treated with conventional management (4.9
      +/- 2.9 vs 16.8 +/- 5.7 micrograms/ml surfactant protein A, respectively, p <
      0.05 by Mann-Whitney U test). CONCLUSIONS: There are decreased surfactant
      components in amniotic fluid in many pregnancies complicated by congenital
      diaphragmatic hernia, which may reflect fetal lung immaturity or hypoplasia.

PMID- 7503178
TI  - Induction of high levels of anticardiolipin antibodies in mice by immunization
      with beta 2-glycoprotein I does not cause fetal death.
AB  - OBJECTIVE: Our purpose was to determine whether anticardiolipin antibodies
      induced by immunization with beta 2-glycoprotein I cause fetal death in mice.
      STUDY DESIGN: Female BALB/c mice were immunized with beta 2-glycoprotein I in a
      carbohydrate adjuvant or with carbohydrate adjuvant alone. The mice were mated
      with BALB/c males and killed on day 11 to 13 of pregnancy, and the fetal status
      was determined. Posttreatment blood samples were obtained for measurement of
      anticardiolipin and anti-beta 2-glycoprotein I antibodies and platelet counts.
      RESULTS: Anticardiolipin and anti-beta 2-glycoprotein I antibodies developed in
      all mice immunized with beta 2-glycoprotein I. Fetal death occurred in 17 of 145
      gestational sacs (12%) in 18 mice immunized with beta 2-glycoprotein I compared
      with 24 of 177 (14%) sacs in 21 control mice. There were no morphometric or
      histologic differences between gestational tissues, and platelet counts were
      similar for each group. CONCLUSIONS: The induction of high levels of
      anticardiolipin antibodies in BALB/c mice by beta 2-glycoprotein I immunizations
      did not result in fetal death or thrombocytopenia. These nonpathogenic beta 2
      glycoprotein I-induced anticardiolipin antibodies should prove useful in the
      characterization of clinically relevant epitopes for antiphospholipid syndrome.

PMID- 7503179
TI  - Routine measurements of umbilical artery lactate levels in the prediction of
      perinatal outcome.
AB  - OBJECTIVE: Our purpose was to compare lactate levels with acid-base balance in
      the umbilical artery with respect to the prediction of pregnancy outcome. STUDY
      DESIGN: A prospective study of 4045 cord samples was performed. Lactate was
      measured with a new method that requires 5 microliters of blood and provides the
      result within 1 minute. RESULTS: The umbilical artery lactate concentrations were
      significantly elevated in instrumental deliveries (2.65 +/- 1.2 mmol/L) and in
      emergency cesarean sections (2.44 +/- 1.7 mmol/L) compared with spontaneous
      vaginal delivery (1.87 +/- 0.94 mmol/L) (p < 0.001, p < 0.001). Lactate
      correlated significantly to fetal pH, hemoglobin, base deficit, PCO2, and HCO3-.
      Lactate was comparable to pH and base deficit in sensitivity, specificity, and
      positive and negative predictive values in relation to morbidity and mortality.
      CONCLUSION: Umbilical artery lactate concentration and acid-base balance
      predicted perinatal outcomes with similar efficacies; however, its simplicity
      makes lactate analysis an interesting alternative in obstetric care.

PMID- 7503180
TI  - Very-low-birth-weight outcomes of the National Institute of Child Health and
      Human Development Neonatal Research Network, May 1991 through December 1992.
AB  - OBJECTIVES: Our goals were to determine the mortality risk for infants weighing
      501 to 1500 gm according to gestational age, birth weight, and gender and to
      document birth weight-related changes in mortality and morbidity over a 5-year
      time period. STUDY DESIGN: In this observational study perinatal data were
      prospectively collected by the 12 participating centers of the National Institute
      of Child Health and Human Development Neonatal Research Network from May 1991
      through December 1992 and compared with the corresponding data from 1987 through
      1990. Standard definitions were used to record sociodemographic factors,
      perinatal events, and the neonatal course to 120 days of life, discharge, or
      death. RESULTS: The 1991 and 1992 cohort included 4279 in-born infants. Among
      their mothers 10% were < 18 years old; 55% were black, 31% were white, and 11%
      were Hispanic; 14% had received no prenatal care; and 20% had received antenatal
      corticosteroids. Multiple gestations accounted for 20% of the births. Fifty
      percent of the infants were delivered by cesarean section. During 1991 and 1992
      the overall survival for infants weighing 501 to 1500 gm at birth was 81%,
      compared with 74% in 1987 and 1988. Survival at birth weight 501 to 750 gm was
      44%; it was 81% at 751 to 1000 gm, 92% at 1001 to 1250 gm, and 95% between 1251
      and 1500 gm. Female infants had a significantly greater chance of surviving than
      male infants at similar birth weights and gestational ages. At any given
      gestational age, smaller infants were less likely to survive. Survival in all
      birth weight categories increased between 1987 and 1992, without accompanying
      increases in medical morbidity. Major morbidity increased with decreasing birth
      weight and included late-onset septicemia 22%, chronic lung disease (oxygen
      dependence at 36 weeks' corrected age) 18%, severe intraventricular hemorrhage
      (grades III and IV) 11%, and necrotizing enterocolitis 5%. Twelve percent of all
      infants were treated with corticosteroids for chronic lung disease, including 36%
      of infants who were oxygen dependent at age 28 days. The mean length of hospital
      stay was 69 days for survivors and 18 days for infants who died. CONCLUSIONS:
      Mortality for infants between 501 and 1500 gm at birth has declined over the past
      5 years. There are interactions between birth weight, gestational age, gender,
      and survival rate. This increase in survival was not accompanied by an increase
      in medical morbidity.

PMID- 7503181
TI  - Evaluation of the Hybrid Capture human papillomavirus deoxyribonucleic acid
      detection test.
AB  - OBJECTIVE: Our purpose was to evaluate the sensitivity and accuracy of a new,
      nonradioactive human papillomavirus deoxyribonucleic acid detection method. STUDY
      DESIGN: Cervical samples from 520 women were assayed for human papillomavirus
      deoxyribonucleic acid with both the Hybrid Capture test and polymerase chain
      reaction. RESULTS: Human papillomavirus deoxyribonucleic acid was detected with
      Hybrid Capture in 106 (42%) of 254 samples from women with no evidence of
      cervical intraepithelial neoplasia and 211 (79%) of 266 with cervical
      intraepithelial lesions or cervical cancer. There was a good correlation between
      Hybrid Capture and polymerase chain reaction. Hybrid Capture correctly identified
      92% of samples found to contain a human papillomavirus type with a high or
      intermediate oncogenic risk with polymerase chain reaction. Although Hybrid
      Capture can quantify the amount of human papillomavirus deoxyribonucleic acid
      present in a sample, no correlation was observed between the relative amount of
      human papillomavirus deoxyribonucleic acid detected with Hybrid Capture and the
      grade of cervical lesion. CONCLUSION: The Hybrid Capture test is a sensitive and
      accurate method for identifying human papillomavirus types of high and
      intermediate oncogenic risk in clinical specimens.

PMID- 7503182
TI  - The emergency contraceptive pill: a survey of knowledge and attitudes among
      students at Princeton University.
AB  - OBJECTIVE: Our purpose was to measure and analyze knowledge and attitudes about
      emergency contraceptive pills. The hypothesis we tested was that more accurate
      knowledge about the regimen would be associated with favorable attitudes towards
      its use. STUDY DESIGN: We conducted a random sample telephone survey and a series
      of focus group discussions at Princeton University (results for 11 focus groups
      are presented elsewhere) A total of 550 undergraduate and graduate students were
      selected randomly for participation in the survey, and the response rate was 82%.
      The study's primary outcome measure was attitudes toward the emergency
      contraceptive pill as a method of fertility control. We used multivariate
      regression analysis with ordered logit models to test the hypothesized
      association between knowledge and attitudes. RESULTS: Basic awareness and
      approval of the emergency contraceptive pill were widespread, yet students lacked
      detailed knowledge, which did contribute to health and ethical misgivings about
      the regimen. Students with accurate information, especially those students who
      knew that the therapy is a large dose of regular oral contraceptives and that
      side effects are generally minor, were significantly more likely than others to
      report favorable attitudes. Many students confused the pills dispensed by the
      university health services (Oral, Wyeth-Ayerst, Philadelphia) with the
      abortifacient RU 486. Students noted discussion of the method is rare, and many
      wanted to know more about it. Statistical results are reported with a 95%
      confidence level. CONCLUSIONS: Educational efforts should offer specific
      information about the composition of emergency contraceptive pills, the side
      effects, and how the regimen works.

PMID- 7503183
TI  - Superior compliance and efficacy of continuous combined oral estrogen-progestogen
      replacement therapy in postmenopausal women.
AB  - OBJECTIVE: We assessed compliance, relief of climacteric symptoms, and impact on
      lumbar bone mineral density in two groups of 140 patients treated with a
      sequential estrogen-progestogen or a continuous combined replacement therapy in
      comparison with controls. STUDY DESIGN: Patients were randomized to 2 mg of
      estradiol valerate daily and 5 mg of medroxyprogesterone acetate daily for 12
      days per month sequentially to induce withdrawal bleeding (group A) or 2 mg of
      estradiol, 1 mg of estriol, and 1 mg of norethisterone acetate daily continuously
      to maintain amenorrhea (group B) or a control group (group C). RESULTS:
      Compliance was 93% after 1 year and 73% after 2 years in group B and 66% and 49%
      in group A after 1 and 2 years, respectively. Improvement of climacteric symptoms
      was similar in groups A and B. Uterine bleeding in 24% of patients in group A and
      3% in group B was the most frequent reason for discontinuation of drug intake.
      Only continuous combined therapy (group B) increased bone mineral density after 1
      and 2 years compared with baseline: +13% and 17% (p = 0.01). In groups A and C no
      significant changes in bone mineral density were recorded. Compliance was
      unrelated to the age of menopause. CONCLUSION: Continuous combined therapy is
      superior to sequential estrogen progestogen replacement in compliance and
      prevention of bone loss but not with regard to relief of climacteric symptoms.

PMID- 7503184
TI  - Clinical indications for hysterectomy route: patient characteristics or physician
      preference?
AB  - OBJECTIVES: Our purpose was to compare the indications, characteristics, surgical
      management, and outcomes of patients undergoing total abdominal hysterectomy,
      total vaginal hysterectomy, and laparoscopically assisted vaginal hysterectomy
      and to assess whether patients who underwent abdominal hysterectomy might have
      been candidates for laparoscopically assisted vaginal hysterectomy and whether
      patients who underwent total abdominal hysterectomy or laparoscopically assisted
      vaginal hysterectomy might have been candidates for total vaginal hysterectomy.
      STUDY DESIGN: The hospital charts of 502 women who underwent elective inpatient
      hysterectomy at a single large general hospital between January 1992 and November
      1993 were abstracted retrospectively by use of a structured data abstraction
      instrument. The study included patients operated on by 16 different experienced
      gynecologists. Data were collected regarding patient demographic characteristics,
      clinical history and preoperative physical examination, indications for surgery,
      route of hysterectomy, intraoperative findings, pathologic study results, and
      outcomes in the immediate postoperative hospitalization period. RESULTS: Patient
      age, race, weight, parity, and previous surgical history were significantly
      associated with hysterectomy type. Although no nulliparous patients and no
      patients with a uterine size estimated preoperatively to be > 12 weeks of
      gestation underwent total vaginal hysterectomy, 16.6% and 30.6% of
      laparoscopically assisted vaginal hysterectomy patients had these
      characteristics, respectively. A total of 6.6% of total abdominal hysterectomy
      cases and 16.7% of laparoscopically assisted vaginal hysterectomy cases lacked an
      obvious justification for an abdominal procedure. On average, surgical time was
      23 minutes longer for laparoscopically assisted vaginal hysterectomy than for
      total abdominal hysterectomy and 30 minutes longer for total abdominal
      hysterectomy than for total vaginal hysterectomy. When uterine size or
      configuration impaired access to uterine vessels, laparoscopically assisted
      vaginal hysterectomy was difficult to perform. Postoperative morbidity was
      similar across the three procedures, but average length of hospital stay was 2.8
      days, 3.5 days, and 4.4 days for laparoscopically assisted vaginal hysterectomy,
      total vaginal hysterectomy, and total abdominal hysterectomy, respectively.
      CONCLUSIONS: Although there are some consistent and statistically significant
      differences in the characteristics of patients undergoing total abdominal
      hysterectomy versus laparoscopically assisted vaginal hysterectomy versus total
      vaginal hysterectomy, laparoscopically assisted vaginal hysterectomy is enabling
      many patients to avoid total abdominal hysterectomy. However, many patients
      undergoing total abdominal hysterectomy and laparoscopically assisted vaginal
      hysterectomy could probably undergo total vaginal hysterectomy instead. Clinical
      outcomes were similar regardless of type of hysterectomy performed. Practice
      style and personal preference of the surgeon thus may be playing a significant
      role in selection of hysterectomy type. Laparoscopically assisted vaginal
      hysterectomy becomes technically difficult and conversion to total abdominal
      hysterectomy is more frequent when uterine size or configuration impairs access
      to uterine vessels.

PMID- 7503185
TI  - Human papillomavirus deoxyribonucleic acid as a prognostic indicator in early
      stage cervical cancer: a possible role for type 18.
AB  - OBJECTIVE: Our purpose was to determine the prognostic significance of human
      papillomavirus deoxyribonucleic acid in cervical cancers. STUDY DESIGN: The
      polymerase chain reaction was used to detect human papillomavirus
      deoxyribonucleic acid types 6, 11, 16, 18, 31, 33, 52, or 58 in tumors from 148
      patients (equal numbers of whom were disease free or had relapses) surgically
      treated for stage IB or IIA cancers in a major Australian hospital. Cox
      regression modeling was used to assess the effect of human papillomavirus status
      on tumor recurrence, taking into account patient age, clinical stage, histologic
      node status, and type of tumor. RESULTS: Seventy of 74 (95%) of the recurring
      tumors and 62 of 74 (84%) of the nonrecurring tumors were human papillomavirus
      deoxyribonucleic acid positive. The rates of positivity of types 16 and 18 were
      64% versus 31% in the recurrers and 65% versus 14% in the nonrecurrers. Human
      papillomavirus type 18 positivity was associated with a greater risk of
      recurrence than was type 16 positivity (hazard ratio 1.8; p = 0.03). Clinical
      stage, nodal metastasis, and young age (< or = 35 years) also had adverse effects
      on relapse (hazard ratio for each approximately 2). CONCLUSION: Human
      papillomavirus type 18 positivity is a risk factor for tumor recurrence in
      surgically treated cervical cancer.

PMID- 7503186
TI  - Transvaginal sacrospinous colpopexy: anatomic landmarks to be aware of to
      minimize complications.
AB  - Transvaginal sacrospinous colpopexy is currently used to repair varying degrees
      of vaginal vault prolapse. It involves placing a stitch from the vaginal cuff to
      the sacrospinous ligament approximately 2 cm medial to the ischial spine to
      correct the defect. This may be associated with pudendal artery and nerve
      (pudendal complex) along with sciatic nerve injury if the procedure is not
      carefully performed. This study was designed to emphasize the anatomic landmarks
      that make the sacrospinous ligament a potentially dangerous zone that surgeons
      must be aware of to minimize complications. Twenty-four female cadavers were
      obtained from the Louisiana State University Medical School anatomy laboratory.
      They were carefully dissected to expose the anatomic structures of interest. The
      following measurements were then obtained: the distance from the ischial spine to
      the medial border of the sacrum, the medial and lateral aspects of the pudendal
      complex, and the sciatic nerve. The obstetric conjugate of the pelves was also
      obtained. The pudendal complex and sciatic nerve were found to be 0.90 to 3.30 cm
      medial to the ischial spine. After the six smallest and largest pelves were
      compared, it was noted that the larger the obstetric conjugate the longer the
      sacrospinous ligament and vice versa. Also, the distance from the ischial spine
      to the sciatic nerve correlated with the size of the obstetric conjugate. The
      pudendal complex and sciatic nerve travel underneath the lateral third of the
      sacrospinous ligament. Therefore we recommend that the placement of the stitch be
      made medial to that portion of the ligament. More importantly, the stitch must be
      placed as superficial as possible and never across the entire thickness of the
      sacropinous ligament. This should decrease the rate of complications associated
      with this type of colpopexy.

PMID- 7503188
TI  - Mutation of tumor suppressor gene p53 is frequently found in vulvar carcinoma
      cells.
AB  - OBJECTIVE: The purpose of this study was to evaluate the presence and type of
      mutations of the tumor suppressor gene p53 in squamous carcinoma cell lines of
      the vulva. STUDY DESIGN: Eight low-passage cell lines established from vulvar
      carcinoma were included in the analysis. Mutational analysis was restricted to
      exons 5 through 9 of the p53 gene, previously shown to have a high incidence of
      mutations. The sequences containing exons 5/6,7, and 8/9 were amplified by
      polymerase chain reaction and screened with a single-strand conformation
      polymorphism technique on PhastSystem (Pharmacia Biotech, Uppsala, Sweden). Exons
      from samples showing mobility shifts in single-strand conformation polymorphism
      were sequenced by polymerase chain reaction direct sequencing. RESULTS: Five
      vulvar carcinoma cell lines showed abnormal electrophoretic mobility of exons
      5/6, one of exons 8/9, and one of exon 7. Reduction to homozygosity was detected
      in four vulvar carcinoma cell lines. Missense mutations were detected by sequence
      analysis in UM-SCV-2 (codon 171: GAG[Glu]-->TAG[STOP]), UM-SCV-3 (hot spot codon
      273: CGT[Arg]-->TGT[Cys]), UM-SCV-4 (codon 151: CCC[Pro]-->CAC[His]), UM-SCV-5
      (codon 155: ACC[Thr]-->ATC[lle]), and UM-SCV-7 (codon 245: GGC[Gly]-->AGC[Ser]).
      UM-SCV-3 also carried a missense mutation with no amino acid change (codon 314:
      TCC[Ser]-->TCT[Ser]). UM-SCV-7 carried an additional base deletion at codon 249
      (AGG-->AG-), likely resulting in a frameshift in transcription and a truncated
      protein product. Four of the seven mutations were transitions, two were
      transversions, and one was a deletion. The presence of transitions suggests that
      at least a proportion of p53 mutations of these cancers may arise spontaneously
      without exogenous carcinogen exposure. UM-SCV-1A and UM-SCV-1B were derived from
      the primary tumor and pleural effusion of the same patient. UM-SCV-6 is a cell
      line that contains human papillomavirus 16. No mutations in these three cell
      lines were found by single-strand conformation polymorphism. CONCLUSIONS: On the
      basis of previous observations, loss of tumor suppressor p53 function either by
      mutation or human papillomavirus involvement is a frequent phenomenon in cervical
      carcinoma cells. It appears now that functional inactivation of p53 is associated
      also with vulvar carcinoma cell lines, but mutations of the p53 gene are much
      more common in vulvar than in cervical carcinoma cell lines.

PMID- 7503187
TI  - Reduction of tumor necrosis factor-alpha bioactivity by a human ovarian
      epithelial cancer cell line in vitro.
AB  - OBJECTIVE: Our purpose was to determine the ability of an ovarian epithelial
      carcinoma cell line, Caov-3, to alter the bioactivity of exogenously added tumor
      necrosis factor-alpha. STUDY DESIGN: Caov-3 cells were cultured for up to 6 days
      in Dulbecco's modified Eagle's medium containing 10% fetal calf serum. The
      control and tumor necrosis factor-alpha-treated cells were analyzed for
      proliferation, distribution throughout the cell cycle by flow cytometry, their
      ability to release bioactive tumor necrosis factor-alpha by L929 bioassay, and
      their ability to release immunoreactive tumor necrosis factor-alpha by a specific
      double sandwich enzyme-linked immunosorbent assay. RESULTS: Tumor necrosis factor
      alpha induced a dose- and time-dependent inhibition of cell proliferation
      accompanied by accumulation of cells in late S and G2/M phases of the cell cycle.
      Tumor necrosis factor-alpha bioactivity was undetectable in the media of control
      Caov-3 cell cultures, but these cells exhibited TNF-alpha messenger ribonucleic
      acid. After culture of the cells for 2 days in the presence of various doses of
      TNF-alpha (0.1, 1.0, 10, or 100 ng/ml), a significant decline (p < 0.01) in
      bioactivity was observed in all groups with the exception of 100 ng of TNF-alpha.
      Further declines in bioactivity were observed 2 and 4 days later. Addition of TNF
      alpha to Caov-3 cells did not affect its immunoactivity, and Western blots of
      media revealed major bands of immunoactivity at approximately 17 kd, the expected
      molecular size of TNF-alpha. CONCLUSION: These results indicate that Caov-3
      ovarian carcinoma cells reduce the bioactivity of TNF-alpha, an important growth
      regulator, by a novel yet unknown mechanism to escape the modulatory effects of
      the normal immune response during cancer cell growth.

PMID- 7503189
TI  - Endothelin-1 and big endothelin-1 increase in human endometrium during
      menstruation.
AB  - OBJECTIVES: Although the physiologic and pathologic roles of endothelin-1 in
      reproduction have been investigated, little is known about human uterine tissue
      levels. We studied the levels of immunoreactive endothelin-1 and immunoreactive
      big endothelin-1 in human endometrium and myometrium during each menstrual phase.
      STUDY DESIGN: Materials were obtained at hysterectomy (endometrium, n = 33;
      myometrium, n = 27). We measured immunoreactive endothelin-1 and immunoreactive
      big endothelin-1 by radioimmunoassay and performed an immunohistochemical study
      of the tissue. Data were analyzed by the Mann-Whitney U test. RESULTS: We
      detected larger amounts of immunoreactive endothelin-1 and immunoreactive big
      endothelin-1 in the endometrium than in the myometrium throughout the menstrual,
      proliferative, and secretory phases. Endometrial immunoreactive endothelin-1 and
      immunoreactive endothelin-1 were significantly increased in the menstrual phase
      (endothelin-1 68.8 +/- 23.3 pg/mg protein, n = 5, p < 0.005; big endothelin-1
      45.2 +/- 5.7 pg/mg protein, n = 5, p < 0.003) compared with the other phases
      (endothelin-1 30.7 +/- 9.5 and 30.5 +/- 14.0 pg/mg protein; big endothelin-1 19.9
      +/- 6.7 and 24.1 +/- 7.4 pg/mg protein). Immunohistochemistry demonstrated that
      the endometrial stromal cells were positive for antiendothelin monoclonal
      antibody only in the premenstrual and menstrual phases. CONCLUSION: Levels of
      immunoreactive endothelin-1 and immunoreactive big endothelin-1 are different in
      each type of uterine tissue and in each phase of the menstrual cycle. These
      changes may indicate some role of endothelin-1 in menstruation.

PMID- 7503191
TI  - A metaanalysis of home uterine activity monitoring.
AB  - OBJECTIVE: Our purpose was to assess by metaanalysis the evidence from randomized
      clinical trials regarding home uterine activity monitoring. STUDY DESIGN: Six
      randomized controlled trials of home uterine activity monitoring, the same six
      trials reviewed by the U.S. Preventive Services Task Force on home uterine
      activity monitoring, were studied. Data were extracted from published reports of
      the six trials. In addition, unpublished data were obtained by personal
      communication from the trials' principal investigators. Insofar as possible, the
      principle of intention-to-treat was maintained. Data regarding twins were handled
      by use of numbers of pregnancies rather than numbers of infants as sample sizes.
      Stratified metaanalyses were conducted according to whether the trial did or did
      not control in study design for the nursing contact factor that accompanies home
      uterine activity monitoring. In addition, stratified metaanalyses were conducted
      for singleton and twin pregnancies. The four outcomes investigated were incidence
      of preterm birth, incidence of preterm labor combined with cervical dilatation >
      2 cm, infant referral to the intensive care unit, and mean birth weight. RESULTS:
      Overall, for all pregnancies home uterine activity monitoring was associated with
      a statistically significant reduction of 52% in risk of preterm labor combined
      with cervical dilatation > 2 cm (relative risk = 0.48, p = 0.001) and a
      statistically significant increase of 86 gm in mean birth weight (p = 0.038).
      When stratified by singleton or twin pregnancy, the pooled results generally
      differed by strata. Among singleton pregnancies, home uterine activity monitoring
      was associated with a statistically significant reduction of 24% in risk of
      preterm birth (relative risk 0.76, p = 0.037) and a statistically significant
      increase of 126 gm in mean birth weight (p = 0.009). Among twin pregnancies,
      there was a statistically significant effect of home uterine activity monitoring
      with a reduction of 56% in risk of preterm labor combined with cervical
      dilatation > 2 cm (relative risk 0.44, p = 0.005). There were no statistically
      significant effects found overall and in any stratum with regard to infant
      referral to the intensive care unit. Metaanalyses of studies that controlled in
      design for the nursing contact factor that accompanies home uterine activity
      monitoring showed either no difference or stronger pooled effects compared with
      metaanalyses of those studies that did not control for nursing contact. This
      suggests that the potential bias attributed to the nursing contact feature that
      accompanies home uterine activity monitoring is not as appreciable as home
      uterine activity monitoring critics have suggested. CONCLUSIONS: Metaanalysis of
      existing clinical trial evidence regarding home uterine activity monitoring
      reveals statistically significant benefits of home uterine activity monitoring.
      Of the outcomes investigated, home uterine activity monitoring is associated with
      reductions in risks of preterm birth (in singleton pregnancies only) and preterm
      labor combined with cervical dilatation > 2 cm, as well as with increased mean
      birth weight (in singleton pregnancies only).

PMID- 7503190
TI  - Lumbar vertebral density and mechanical properties in aged ovariectomized rats
      treated with estrogen and norethindrone or norgestimate.
AB  - OBJECTIVE: This study was designed to investigate the effects of estrogen alone
      or combined with two different progestins, norethindrone or norgestimate, on bone
      density and compressive mechanical properties in an aged rat model. STUDY DESIGN:
      Twenty 11-month-old female Sprague-Dawley rats were sham operated (intact
      control) and 80 wee ovariectomized. Three groups of 20 ovariectomized rats were
      implanted with Silastic silicon rubber (Dow Corning, Midland, Mich.) capsules
      containing 5% estradiol (wt/wt) in cholesterol. All rats in the intact control
      (group 1) and the ovariectomized (group 2) and the first of the ovariectomized
      plus estrogen (group 3) groups were injected subcutaneously daily for 6 months
      with corn oil (vehicle). Two other groups of rats with estrogen capsules received
      daily injections of norethindrone (3 micrograms/rat/day) or norgestimate (1.5
      micrograms/rat/day) in corn oil for 3 days out of every 6 days (interrupted
      progestin). The effects of these various treatments on bone mineral content and
      bone mineral density in the vertebrae were measured by dual energy x-ray
      absorptiometry. The L4 vertebral bodies were also tested to failure in
      compression. RESULTS: The ovariectomized rats receiving corn oil alone had the
      lowest bone mineral density compared with intact controls. Estrogen treatment
      alone resulted in a lower bone mineral density than in the intact controls. In
      contrast, both interrupted progestin regimens resulted in vertebral bone mass
      index at the same level as the intact controls. Compression tests revealed that
      ovariectomized controls also had the lowest modulus of elasticity of all groups.
      However, unlike bone mineral density, estrogen alone resulted in mechanical
      properties similar to intact controls, whereas the vertebrae in both interrupted
      progestin groups had variable mechanical properties compared with the
      ovariectomized and intact control groups. CONCLUSIONS: We conclude that in this
      experimental model hormone replacement therapy with estrogen and an androgenic
      (norethindrone) or nonadrogenic (norgestimate) progestin result in similar bone
      mineral density and mechanical properties. In addition, both interrupted
      progestin regimens had a better effect than estrogen alone on vertebral bone
      density.

PMID- 7503192
TI  - Elevated protease activities in human amnion and chorion correlate with preterm
      premature rupture of membranes.
AB  - OBJECTIVES: The mechanism(s) of preterm premature rupture of fetal membranes
      resulting in preterm birth remains unknown. Studies suggest that fetal membranes
      are susceptible to weakening by protease attack and that collagenases may be
      active at the site of rupture. In this study fetal membranes from women delivered
      after preterm premature rupture of membranes were compared with control membranes
      and analyzed qualitatively and quantitatively for protease activities. STUDY
      DESIGN: Fourteen membranes from women with preterm premature rupture of membranes
      and nine membranes from women delivered preterm without premature rupture of
      membranes or otherwise normal women delivered at term vaginally or by cesarean
      section were studied. Zymogram gel electrophoresis with gelatin incorporation was
      used to assess the number and apparent molecular weights of protease activities.
      Functional and quantitative studies of protease activity were measured by
      fluorescent substrate cleavage. RESULTS: Zymogram gel electrophoresis studies
      demonstrated the presence of five to seven different protease bands in preterm
      premature rupture of membranes samples, whereas control membranes demonstrated
      only one to three protease bands. Fluorescent studies of protease activity
      demonstrated a 10- to 40-fold increase in activity in membranes from women with
      preterm premature rupture of membranes compared with normal control membranes.
      Studies with protease inhibitors suggest that most of the activity is due to
      metalloproteinases. CONCLUSION: In membranes from women with preterm premature
      rupture of membranes there appears to be a general increase in the amount of
      protease activity and increased numbers of putatively different proteases.
      Increased activity or deregulated protease control may mediate preterm premature
      rupture of membranes and be a potentially remediable cause of preterm birth.

PMID- 7503194
TI  - Oral terbutaline in the outpatient management of preterm labor.
AB  - OBJECTIVE: Our purpose was to prove our hypothesis that once preterm uterine
      contractions and/or labor is controlled with intravenous tocolysis, oral
      terbutaline, as a maintenance drug, does not prolong pregnancy. STUDY DESIGN:
      Before discharge, 184 patients between 24 and 35 completed weeks' gestation were
      prospectively randomized to continued bed rest either with or without oral
      terbutaline. Assignment was made with stratification into four groups: group 1,
      those patients with a Bishop score > or = 5 with oral terbutaline (n = 50); group
      2, those with a Bishop score > or = 5 without oral terbutaline (n = 53); group 3,
      those with a Bishop score < 5 with oral terbutaline (n = 41); group 4, those with
      a Bishop score < 5 without oral terbutaline (n = 40). Oral terbutaline was
      discontinued at 37 completed weeks. RESULTS: No statistically significant
      differences were found in the number of readmissions, the number of unscheduled
      hospital visits, and the neonatal outcomes among the four groups. The gestational
      age at delivery and percent of deliveries at > or = 37 weeks were not
      significantly different when group 1 was compared with group 2 and group 3 was
      compared with group 4. CONCLUSION: Oral terbutaline maintenance does not improve
      pregnancy outcome in patients who have had initial successful intravenous
      tocolysis.

PMID- 7503193
TI  - Fetal fibronectin as a selection criterion for induction of term labor.
AB  - OBJECTIVE: We examined whether the presence of fetal fibronectin in
      cervicovaginal secretions can be used as a selection criterion for induction of
      labor at term. STUDY DESIGN: Cervicovaginal secretions of 64 women who were
      scheduled for induction of labor were examined for fetal fibronectin and divided
      into group A (positive for fibronectin) and group B (negative for fibronectin).
      Both groups were examined for Bishop score, the number of prostaglandin tablets
      administered, and the interval between induction of labor and delivery. RESULTS:
      In group A the interval between induction of labor and delivery was significantly
      shorter (p < 0.0001) than in group B. The number of prostaglandin tablets
      administered to group A was likewise significantly lower (p < 0.0001).
      Unsuccessful induction of labor only occurred in women with fibronectin-negative
      cervicovaginal secretions. CONCLUSION: The assessment of the fibronectin content
      of cervicovaginal secretions constitutes a viable instrument in the decision
      making process preceding induction of labor.

PMID- 7503195
TI  - Is polyhydramnios in an ultrasonographically normal fetus an indication for
      genetic evaluation?
AB  - OBJECTIVE: Our purpose was to determine the frequency of fetal chromosomal
      anomalies in pregnancies complicated by polyhydramnios. STUDY DESIGN: Between
      Jan. 1, 1992, and July 31, 1993, an amniotic fluid index was measured
      prospectively in 2730 third-trimester pregnant women. Polyhydramnios was defined
      as an amniotic fluid index > or = 24 cm. A computer search identified all infants
      born with structural or chromosomal anomalies. RESULTS: Polyhydramnios was
      detected in 49 of 2730 women (1.7%). The incidence of chromosomal anomalies was
      two in 49 (4.1%) compared with three in 2681 (0.12%) among women with normal
      fluid (p < 0.05). Six of the 49 newborns had structural anomalies (12.2%),
      whereas 48 of 2681 (1.8%) structural anomalies occurred in the control group (p <
      0.05). Among study patients both fetuses with chromosomal anomalies were growth
      retarded; four of the six structural anomalies were associated with an amniotic
      fluid index > 30 cm. CONCLUSIONS: (1) Polyhydramnios is associated with an
      increased incidence of congenital fetal anomalies. (2) Growth-retarded fetuses
      with polyhydramnios warrant genetic evaluation. (3) A genetic study is not
      absolutely indicated for patients with polyhydramnios and a sonographically
      normal fetus.

PMID- 7503196
TI  - Intravaginal clindamycin treatment for bacterial vaginosis: effects on preterm
      delivery and low birth weight.
AB  - OBJECTIVE: Our goal was to evaluate whether treatment of bacterial vaginosis
      during pregnancy with 2% clindamycin vaginal cream reduces the incidence of
      either preterm delivery or low birth weight or of both. STUDY DESIGN: A
      multicenter, double-blind, randomized, placebo-controlled trial in Indonesia
      compared a 2% clindamycin vaginal cream with a placebo cream. Women seeking
      prenatal care at 14 to 26 weeks of gestational age who had bacterial vaginosis
      (Gram stain score > 6 and pH of vaginal fluid > 4.5) were invited to participate.
      Of the 745 women enrolled, 681 (91.4%) women were followed up through delivery.
      RESULTS: Clindamycin vaginal cream was an effective treatment for bacterial
      vaginosis. Two weeks after completion of the treatment, 85.5% of the women were
      cured. The rate of preterm delivery (< 37 weeks) was 15.0% for clindamycin
      patients and 13.5% for placebo patients (odds ratio 1.1, 95% confidence interval
      0.7 to 1.7). The rate of low birth weight was 9.0% for clindamycin patients and
      6.8% for placebo patients (odds ratio 1.3, 95% confidence interval 0.8 to 2.4).
      CONCLUSIONS: Treatment of bacterial vaginosis with clindamycin vaginal cream did
      not reduce preterm delivery or low birth weight. Although clindamycin vaginal
      cream is an effective treatment for bacterial vaginosis, intravaginal treatment
      would not be effective against bacterial vaginosis-associated microorganisms
      harbored in the upper genital tract. Systemic treatment may be required to
      eradicate upper tract infection to reduce preterm delivery.

PMID- 7503197
TI  - Antepartum surveillance in diabetic pregnancies: predictors of fetal distress in
      labor.
AB  - OBJECTIVE: Our purpose was to evaluate an antepartum testing program based on
      twice-weekly nonstress testing and amniotic fluid evaluation in pregnancies
      complicated by diabetes mellitus and to weight the test components in the
      prediction of fetal distress requiring cesarean delivery. STUDY DESIGN: During
      the 4-year period of 1987 through 1990, 2134 women with pregnancies complicated
      by diabetes underwent antepartum testing. Of these 1501 women (class A1, n = 505;
      A2-diet, n = 305; A2-insulin, n = 580; B, n = 71; C to D, n = 29; R to F, n = 11)
      were delivered within 4 days of their last test. Categoric analysis of data was
      performed according to diabetic class, fetal heart rate results, and the presence
      of decreased, normal, or increased amniotic fluid assessment. A univariate
      logistical regression was first conducted with cesarean delivery for fetal
      distress as outcome variable by use of the following variables: fetal weight and
      sex, diabetic class, gestational age at delivery, presence of additional
      indications for antepartum testing, largest vertical pocket, amniotic fluid index
      (summation of the four quadrants of the largest vertical pocket), nonstress test
      reactivity (two accelerations of > or = 15 beats/min of 15 seconds' duration),
      presence of decelerations (> or = 15 beats/min for 15 seconds) during the
      nonstress test, and the interactions of the nonstress test with deceleration,
      largest vertical pocket, and amniotic fluid index. Multivariate analysis was then
      applied to predict the best model. RESULTS: No stillbirths occurred within 4 days
      of the last antepartum test. However, the corrected stillbirth rate of the entire
      tested population was 1.4 per 1000. Eighty-five women required cesarean delivery
      for fetal distress. The factors most predictive of cesarean delivery for fetal
      distress (p < 0.05, odds ratio and 95% confidence interval) were a deceleration
      (3.60, 2.14 to 6.06), nonreactive nonstress test (2.68, 1.60 to 4.49), and the
      interaction of both a nonreactive nonstress test and decelerations (5.63, 2.67 to
      11.9). Amniotic fluid assessment by largest vertical pocket or amniotic fluid
      index were not statistically significant. The multivariate analysis selected the
      interaction of nonstress test and deceleration as the best significant predictor
      for cesarean delivery for fetal distress. CONCLUSION: An antepartum fetal
      surveillance program using twice-weekly nonstress test and fluid index assessment
      in pregnancies complicated by diabetes was successful in preventing stillbirth.
      The absence of fetal heart rate reactivity and the presence of decelerations were
      predictive of the diagnosis of fetal distress in labor requiring cesarean
      delivery. Ultrasonographic assessment of amniotic fluid volume was not a
      significant predictor of fetal distress in labor in the diabetic pregnancy.

PMID- 7503199
TI  - Ultrasonographic measurement of the dividing membrane in twin pregnancy during
      the second and third trimesters: a reproducibility study.
AB  - OBJECTIVE: Our purpose was to examine the reproducibility of intertwin membrane
      thickness measurements used to predict chorionicity in twin pregnancies. STUDY
      DESIGN: Twenty-seven twin pregnancies were scanned with high-resolution
      ultrasonography on 52 occasions during the second and third trimesters. Two
      observers, blind to other criteria of chorionicity, measured the dividing
      membrane twice in five different sites (total measurements 1040). The data were
      log-transformed and the coefficient of repeatability calculated as a measure of
      intraobserver variability. Interobserver variability was estimated by the Bland
      and Altman 95% limits of agreement. Random variation was assessed with the
      restricted maximum likelihood procedure in Genstat. RESULTS: The overall estimate
      of the coefficient of repeatability was 2.14, indicating that 95% of repeated
      measurements would be expected to be within 114% of each other. Measurements
      taken close to the placenta (up to 3 cm) were the most repeatable and displayed
      no bias when repeated. Coefficients of repeatability at this site ranged from
      1.42 to 1.91, with no evidence of consistent differences between monochorionic
      and dichorionic twins. Gestational age was not significantly associated with
      membrane thickness for any of the models. The pregnancy type x subject x observer
      and pregnancy type x subject x site interactions were statistically significant
      (p < 0.001 and p < 0.005, respectively), implying that interobserver variability
      depends on the subject being measured, the site of sampling, and chorionicity.
      CONCLUSION: Ultrasonographic measurement of membrane thickness has high
      intraobserver and interobserver variability in the second and third trimesters.
      Our findings provide an explanation for the suboptimal accuracy reported with
      this method in determining chorionicity in the second and third trimesters.

PMID- 7503198
TI  - Estrogen increases nitric oxide synthase activity in the uterus of nonpregnant
      sheep.
AB  - OBJECTIVE: The aim of this study was to characterize nitric oxide synthase
      activity in endometrium and myometrium of nonpregnant sheep and to determine
      whether estrogen administration affects uterine nitric oxide synthase activity.
      STUDY DESIGN: Nonpregnant sheep were castrated during synchronized estrus and 4
      days after surgery were treated with 100 micrograms/day of 17 beta-estradiol for
      3 days. Nitric oxide synthase activity was measured by the citrulline conversion
      assay. RESULTS: Citrulline generation found in soluble and particulate fractions
      had all the characteristics of nitric oxide synthase, namely, it was strictly
      dependent on reduced nicotinamide adenine dinucleotide phosphate and enhanced by
      flavin nucleotides and tetrahydrobiopterin. Estrogen administration significantly
      increased Ca(++)-dependent nitric oxide synthase activity in myometrium but not
      in endometrium. The effect of estrogen was more pronounced in the membrane
      associated enzyme activity (approximately fivefold). Estrogen treatment increased
      myometrial nitric oxide synthase activity from 9.0 +/- 2.4 to 20.0 +/- 3.7
      pmol/mg of protein per 30 minutes in the soluble fraction and from 12.0 +/- 5.1
      to 62.0 +/- 13.1 pmol/mg of protein per 30 minutes in the particulate fraction
      (mean +/- SEM, p < 0.05 by t test). The increase in nitric oxide synthase
      activity was not mediated by an increase in tetrahydrobiopterin availability, as
      shown to be the case in macrophages. CONCLUSION: These data show that in the
      nonpregnant sheep uterus > 90% of the nitric oxide synthase activity found in
      myometrium is Ca++ dependent and is up-regulated by estrogen in a tissue-specific
      manner.

PMID- 7503200
TI  - Changes in rat cervical collagen during gestation and after antiprogesterone
      treatment as measured in vivo with light-induced autofluorescence.
AB  - OBJECTIVE: This study was conducted to evaluate use of light-induced
      autofluorescence for measuring changes in collagen of cervical connective tissue
      during gestation. STUDY DESIGN: In a conventional laboratory setting light
      induced autofluorescence from the cervix of Charles-Dawley timed pregnant rats
      was measured in vivo. Eight distinct groups at various times of gestation were
      examined. Measurements were also performed on rats at day 17 of gestation 24
      hours after treatment with RU 38486. RESULTS: The amount of light-induced
      autofluorescence decreases significantly as pregnancy approaches term (means of
      the arbitrary total counts per spectrum on day 19 vs day 21 = 2.8 x 10(5) vs 1.9
      x 10(5), p < 0.01) and reaches its lowest point when the pups are engaged in the
      cervix (day 19 vs day 22 = 2.8 x 10(5) vs 0.95 x 10(5), p < 0.001) and during
      delivery (day 19 vs day 22 = 2.8 x 10(5) vs 0.95 x 10(5), p < 0.001) and during
      delivery (day 19 vs delivery = 2.8 x 10(5) vs 0.83 x 10(5), p < 0.001). Preterm
      treatment with RU 38486 also caused a significant decrease in the native
      fluorescence compared with vehicle-injected controls (day 17 control vs day 17 RU
      38486 = 2.8 x 10(5) vs 1.5 x 10(5), p < 0.001). CONCLUSION: Significant decreases
      in cervical collagen at parturition parallel the results of previous studies that
      used various indirect methods to analyze collagen content. These data support the
      use of light-induced autofluorescence for detecting and studying the changes in
      cervical and uterine connective tissue during gestation in vivo.

PMID- 7503201
TI  - Secretion of prostaglandins and endothelin-1 by decidual endothelial cells from
      normal and preeclamptic pregnancies: comparison with human umbilical vein
      endothelial cells.
AB  - OBJECTIVE: An increasing amount of circumstantial evidence points to the maternal
      endothelial cell as centrally involved in the syndrome of preeclampsia. The
      purposes of this study were (1) to compare the secretion of vasoactive substances
      by maternal decidual endothelial cells with that of umbilical vein endothelial
      cells, widely used as a surrogate for endothelial cells in general, and (2) to
      compare secretion of the same vasoactive substances by decidual endothelial cells
      from normal and preeclamptic pregnancies. STUDY DESIGN: Endothelial cells were
      isolated from umbilical veins and from decidual biopsy specimens collected at
      cesarean section delivery from both normal and preeclamptic women. Cells were
      maintained in culture until passage 2, when secretion by the three endothelial
      cell populations of the vasodilators prostaglandin E2 and prostacyclin and the
      vasoconstrictor endothelin-1 was examined. In addition to control incubations,
      their responses to stimulation and suppression of secretion were compared.
      RESULTS: In control incubations normal decidual endothelial cells secreted lower
      amounts of prostacyclin, prostaglandin E2, and endothelin than did human
      umbilical vein endothelial cells. All cell types had qualitatively similar
      responses to the stimuli used, but quantitatively different responses were noted
      between human umbilical vein endothelial cells and normal decidual endothelial
      cells for all metabolites examined. Preeclamptic decidual endothelial cells
      secreted significantly more prostaglandin E2 than did normal decidual endothelial
      cells in response to stimulation. CONCLUSIONS: We have delineated levels of
      secretion of vasoactive substances by human late pregnancy decidual endothelial
      cells and their responses to manipulation of secretory pathways. There are
      differences between this endothelial cell population and human umbilical vein
      endothelial cells (which are widely used as a surrogate for maternal endothelial
      cells). The differences between normal and preeclamptic decidual endothelial
      cells in prostaglandin E2 secretion may point to altered regulation of
      arachidonic acid metabolic pathways in preeclampsia.

PMID- 7503202
TI  - Prevalence of antibodies to glutamic acid decarboxylase in women who have had
      gestational diabetes.
AB  - OBJECTIVES: Our purpose was to determine the prevalence of autoantibodies to
      glutamic acid decarboxylase in women who had had gestational diabetes, including
      those in whom insulin-requiring or non-insulin-requiring diabetes mellitus has
      since developed. STUDY DESIGN: The study group comprised 734 women with previous
      gestational diabetes who were consecutive attendees to a follow-up clinic. These
      women were tested for autoantibodies to glutamic acid decarboxylase with a
      radioimmunoprecipitation assay. We similarly tested 104 women in whom permanent
      diabetes mellitus developed after gestational diabetes, of whom 20 were using
      insulin and 84 were not. Those using insulin also had fasting C-peptide levels
      measured. RESULTS: Thirteen of the 734 (1.8%, 95% confidence interval 0.9% to
      3.0%) women with previous gestational diabetes were positive for autoantibodies
      to glutamic acid decarboxylase. Of the 20 women with diabetes treated with
      insulin, 12 had insulin deficiency confirmed by low levels of C peptide; all 12
      were positive for autoantibodies to glutamic acid decarboxylase. Of the 84 women
      with diabetes not requiring insulin, 6 (7.1%, 95% confidence interval 2.7% to
      14.9%) were positive for autoantibodies to glutamic acid decarboxylase.
      CONCLUSIONS: The prevalence of autoantibodies to glutamic acid decarboxylase in
      women with previous gestational diabetes was 1.8%. Our data also showed that
      insulin-dependent diabetes mellitus will develop in 1.7% of women with
      gestational diabetes. A positive test for autoantibodies to glutamic acid
      decarboxylase may help in the early identification of insulin-dependent diabetes
      mellitus. Adult-onset insulin-dependent diabetes mellitus developed in only 5.2%
      (12/230) of women with previous gestational diabetes who later had diabetes
      mellitus.

PMID- 7503203
TI  - Immunolocalization of progesterone-induced uterine protein-1 in human endometrium
      during the menstrual cycle and in the placenta throughout gestation.
AB  - OBJECTIVE: Progesterone-induced uterine protein-1, a product of secretory
      endometrial stromal cells (relative molecular mass 70,000, isoelectric point
      5.7), was immunolocalized in endometrium and placenta. STUDY DESIGN: Biopsies
      were performed to obtain human endometrium and placenta throughout the menstrual
      cycle and gestation. Formalin-fixed, paraffin-embedded tissues (n = 74) were
      sectioned and immunohistochemically stained for progesterone-induced uterine
      protein-1 by the avidin-biotin peroxidase procedure. Isolated endometrial cells
      were also stained for progesterone-induced uterine protein-1. RESULTS:
      Progesterone-induced uterine protein-1 localized in proliferative endometrial
      stroma and in early to midsecretory stroma and ciliated epithelia and vanished
      from nonpregnant, late-secretory endometrium yet localized in the decidua,
      syncytiotrophoblast, and intermediate cytotrophoblast during pregnancy. Isolated,
      cultured endometrial stromal but not epithelial cells displayed progesterone
      induced uterine protein-1 staining. CONCLUSION: Endometrial progesterone-induced
      uterine protein-1 localization shifts from stromal to epithelial, coinciding with
      the time of ovulation, fertilization, and implantation. This observation,
      combined with the disappearance of progesterone-induced uterine protein-1 in late
      secretory, nonpregnant endometrium and its presence in decidua and trophoblast,
      suggests that progesterone-induced uterine protein-1 may play a role in
      decidualization, endometrial or embryo cross-talk, or placental physiologic
      features.

PMID- 7503205
TI  - Recent changes in delivery site of low-birth-weight infants in Washington: impact
      on birth weight-specific mortality.
AB  - OBJECTIVES: Our purpose was to ascertain whether the proportion of low-birth
      weight infants delivered in Washington at tertiary hospitals changed between 1980
      and 1991 and whether mortality differed by level of birth hospital. STUDY DESIGN:
      A retrospective cohort study was performed of 500 to 2499 gm infants born to
      Washington residents between 1980 and 1991 (n = 43,228). RESULTS: Overall, the
      percentage of low-birth-weight infants born at tertiary centers rose from 1980 to
      1982 through 1986 to 1988 and subsequently declined significantly. Among infants
      weighing < 2000 gm nontertiary delivery was associated with greater potentially
      preventable mortality (500 to 999 gm, relative risk 1.5, 95% confidence interval
      1.3 to 1.8; 1000 to 1499 gm, relative risk 2.1, 95% confidence interval 1.3 to
      3.3; 1500 to 1999 gm, relative risk 1.6, 95% confidence interval 1.0 to 2.6).
      Nontertiary delivery of 2000 to 2499 gm infants was associated with lower overall
      mortality (relative risk 0.5, 95% confidence interval 0.3 to 0.8), but higher
      risk deliveries in this birth weight range were apparently concentrated at
      tertiary hospitals. CONCLUSIONS: In light of the apparent benefit of tertiary
      center birth for infants weighing < 2000 gm, the possible erosion of effective
      regionalized perinatal care networks should be monitored closely.

PMID- 7503204
TI  - A randomized trial comparing misoprostol three and seven days after methotrexate
      for early abortion.
AB  - OBJECTIVE: Our purpose was to determine whether vaginal misoprostol 7 days rather
      than 3 days after methotrexate injection increases the percent of successful
      abortions on the day of misoprostol administration. STUDY DESIGN: A randomized
      controlled trial was performed in women requesting an abortion at < or = 56 days'
      gestation. Eighty-six women were treated with methotrexate 50 mg/m2
      intramuscularly followed 3 days (group 1) or 7 days (group 2) later by vaginal
      misoprostol 800 micrograms. The misoprostol dose was repeated if the abortion did
      not occur. RESULTS: Complete abortion occurred in 38 of 46 (83%) patients in
      group 1 and 39 of 40 (98%) in group 2 (p = 0.033). Of the women with complete
      abortions, 30 of 46 (65%) in group 1 and 27 of 40 (68%) in group 2 aborted the
      same day as the first or second dose of misoprostol (p = 0.823). Vaginal bleeding
      lasted 14 +/- 5 (mean +/- SD) days in group 1 and 17 +/- 9 days in group 2. The
      remaining women aborted after a delay of 24 +/- 6 days in group 1 and 28 +/- 13
      days in group 2. For these women vaginal bleeding lasted 18 +/- 17 and 14 +/- 7
      days, respectively, and the human chorionic gonadotropin-beta level was < or = 25
      IU/L by 22 +/- 7 days after the abortion in group 1 and 19 +/- 9 days in group 2.
      Treatment failures in group 1 were four continuing pregnancies (9%), two
      incomplete abortions (4%), and two women who requested surgical termination after
      receiving both medications (4%). The treatment failure in group 2 was an
      incomplete abortion. Methotrexate and misoprostol side effects were infrequent.
      CONCLUSIONS: Methotrexate and vaginal misoprostol are more effective
      abortifacients when the misoprostol is given 7 days rather than 3 days after
      methotrexate. This treatment regimen may offer an alternative to surgical
      abortion or the use of antiprogestins and prostaglandin for medical abortion.

PMID- 7503207
TI  - A prospective longitudinal evaluation of pregnancy in the Marfan syndrome.
AB  - OBJECTIVE: We undertook a prospective evaluation of the outcomes of pregnancy,
      both maternal and fetal, and the long-term impact of pregnancy on Marfan syndrome
      in a series of consecutive, unselected patients. STUDY DESIGN: Forty-five
      pregnancies in 21 Marfan syndrome patients were prospectively observed in one
      institution between 1983 and 1992. During pregnancy, patients were monitored with
      serial echocardiograms and close attention to symptoms. Maternal and fetal
      outcomes were monitored with serial echocardiographic data were analyzed by least
      squares regression. Eighteen of the patients were followed up for 15 months to 13
      years after the completion of their last pregnancy for investigation of the long
      term impact of pregnancy on the cardiovascular manifestations of Marfan syndrome.
      RESULTS: Aortic dissection occurred in two patients, both with increased risk for
      dissection established before pregnancy. The incidence of obstetric complications
      otherwise did not exceed that in the general population. Echocardiographic data
      demonstrated little to no change in aortic root diameter throughout pregnancy in
      most patients. Long-term follow-up showed no apparent worsening of cardiovascular
      status attributable to pregnancy in comparison with a group of 18 women with
      Marfan syndrome who were of similar age, had a similar degree of disease
      severity, and underwent no pregnancies. CONCLUSIONS: Patients with Marfan
      syndrome in whom cardiovascular involvement is minor and aortic root diameter is
      < 40 mm usually tolerate pregnancy well, with favorable maternal and fetal
      outcomes, and without subsequent evidence of aggravated aortic root dilatation
      over time.

PMID- 7503206
TI  - Fetal responses to maternal and fetal methamphetamine administration in sheep.
AB  - OBJECTIVES: The current study was designed to test the hypothesis that maternally
      administered methamphetamine decreases fetal PaO2 by reducing uterine blood flow
      and to determine the cardiovascular and blood gas responses to varying doses of
      methamphetamine given both to the fetus and the mother. STUDY DESIGN: Nine near
      term pregnant sheep were surgically instrumented to measure maternal and fetal
      blood pressure and heart rate and uterine and umbilical blood flow. Fetal blood
      gases and pH were determined before and after each dose of methamphetamine.
      Methamphetamine was administered as intravenous bolus injections (30 to 35
      minutes separating administration of each dose) into the maternal femoral vein in
      increasing doses of 0.03, 0.1, 0.3, and 1.0 mg/kg and on a separate days to the
      fetus into the hind limb vein as doses of 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg
      estimated fetal weight. RESULTS: Maternal methamphetamine administration produced
      a dose-related increase in maternal and fetal blood pressure and uterine vascular
      resistance, whereas uterine blood flow decreased in a dose-related fashion.
      Umbilical blood flow tended to increase slightly, but this did not reach
      significance. Fetal PaO2 decreased significantly, whereas fetal pH decreased only
      modestly. Direct fetal administration of methamphetamine produced dose-related
      increases in fetal blood pressure and umbilical blood flow and a significant
      decrease in fetal pH but no change in fetal PaO2. CONCLUSIONS: The fetal PaO2
      decrease observed after maternal administration of methamphetamine appears to be
      a result of decreased uteroplacental perfusion, whereas the observed changes in
      fetal blood pressure and fetal pH appear to be a result of the direct action of
      methamphetamine on the fetus.

PMID- 7503208
TI  - Breast-feeding education of obstetrics-gynecology residents and practitioners.
AB  - OBJECTIVE: Our purpose was to assess breast-feeding education, knowledge,
      attitudes, and practices among resident and practicing obstetrician
      gynecologists. STUDY DESIGN: A mailed survey was administered to a national
      sample of resident and practicing obstetrician-gynecologists. RESULTS: Response
      rates were 64% for residents and 69% for practitioners. Residency training
      included limited opportunity for direct patient interaction regarding breast
      feeding; 60% of practitioners recommended that training devote more time to
      breast-feeding counseling skills. Only 38% of residents reported that obstetric
      faculty presented breast-feeding topics; more common sources were nursing staff
      and other residents. Practitioners rated themselves as more effective in meeting
      the needs of breast-feeding patients than were residents; prior personal breast
      feeding experience was a significant influence on perceived effectiveness. Almost
      all respondents agreed that obstretician-gynecologists have a role in breast
      feeding promotion, but significant deficits in knowledge of breast-feeding
      benefits and clinical management were found. CONCLUSION: Residency training and
      continuing education programs should create opportunities to practice breast
      feeding promotion skills and emphasize management of common lactation problems.

PMID- 7503209
TI  - Changes in health care delivery: a threat to academic obstetrics.
AB  - OBJECTIVE: Our purpose was to examine the effect of anticipated health care
      policy changes on delivery trends at leading academic obstetric institutions.
      STUDY DESIGN: The 51 centers in the United States with the most Society of
      Perinatal Obstetricians presentations in the past 2 years were surveyed regarding
      annual deliveries from 1990 to 1993 and reasons for any changes. Analysis of
      variance and chi 2 analysis were used as appropriate. RESULTS: Complete data were
      available from 43 hospitals representing 39 institutions. Their 1990 to 1993
      delivery rates declined faster than United States delivery rates (12.3% vs 2.0%,
      p < 0.0001). The largest hospitals (> 6000 deliveries) had a decline of 18.2%
      compared with declines of 9.0% for medium and 0.9% for small hospitals (< 2500
      deliveries). Regionally the greatest impact was seen in the West and the South,
      with 22% and 12% declines, respectively (p < 0.05). Reasons cited for the decline
      included competition from private or community physicians or hospitals (59%) and
      managed care (15%). CONCLUSION: As the national health care debate focuses on
      cost containment and coverage, we believe the potential effects of national
      policy on research and education should be considered. Continued selective
      reduction in deliveries at academic institutions can be expected to adversely
      affect research and education.

PMID- 7503210
TI  - De formato foetu.

PMID- 7503211
TI  - Obstetric outcome after failed termination of pregnancy--a report of two cases.
AB  - Unsuccessful therapeutic abortion resulting in continued viability of the fetus
      is rare. No case of a live birth after unsuccessful vacuum curettage has been
      published. We report two cases with persistent pregnancies after failed
      termination, with outcomes complicated by premature rupture of membranes and
      preterm delivery.

PMID- 7503212
TI  - Achondrogenesis type I diagnosed by transvaginal ultrasonography at 13 weeks'
      gestation.
AB  - We present the first transvaginal first-trimester diagnosis of achondrogenesis
      type I confirmed by radiographic and histologic studies. The ultrasonographic
      signs included severe short limb mesomelic dwarfism, large head with decreased
      ossification, and lack of vertebral ossification.

PMID- 7503214
TI  - Disposition of maternal ketoconazole in breast milk.
AB  - Infant exposure to ketoconazole in human milk was calculated to be 0.4% on
      average (maximum 1.4%) of those expected from therapeutic doses given directly to
      infants. Potential risk of adverse reactions from this low exposure level seem to
      be outweighed by the benefits of breast-feeding.

PMID- 7503213
TI  - Supernumerary ovary with an endometrioma and osseous metaplasia: a case report.
AB  - A 32-year-old-woman with a history of endometriosis and chronic pelvic pain had
      left-sided pain and ultrasonographic documentation of a left pelvic complex cyst
      approximately 5 cm in diameter. Laparotomy revealed a left retroperitoneal cystic
      mass adjacent to the iliopsoas muscle and overlying the major pelvic vessels. The
      mass was dissected and excised. Histopathologic study revealed endometrioma and
      osseous metaplasia in a supernumerary ovary.

PMID- 7503216
TI  - Galactorrhea caused by esophagitis.
AB  - A case of galactorrhea caused by painful esophagitis, a previously unreported
      etiology, is presented. The galactorrhea promptly resolved with appropriate
      treatment of the esophagitis. It is proposed that the mechanism of production of
      galactorrhea is similar to that seen with chest wall lesions. This cause should
      be kept in mind when evaluating unusual causes of galactorrhea.

PMID- 7503215
TI  - Pregnancy complicated by cerebral venous thrombosis in Behcet's disease.
AB  - Pregnancy and Behcet's disease are both disorders with increased risks of
      cerebral venous thrombosis. However, we describe the first case of central venous
      thrombosis during the pregnancy of a woman with Behcet's disease, revealed by
      headaches, visual obscuring, and a slight increase in cerebrospinal fluid opening
      pressure. Treatment with heparin and corticosteroids led to rapid amelioration.

PMID- 7503217
TI  - Gastrointestinal hemorrhage during pregnancy in a patient with a history of
      vertical-banded gastroplasty.
AB  - Pregnancy after gastric bypass for morbid obesity is well reported; however, the
      only maternal complications described have involved nutritional deficiencies. We
      report a case of gastrointestinal hemorrhage during pregnancy resulting from
      erosion of a synthetic graft from a vertical-banded gastroplasty performed 4
      years previously.

PMID- 7503218
TI  - Ballantyne syndrome caused by a large placental chorioangioma.
AB  - Ballantyne syndrome has been found in association with a number of antenatal
      complications. This first reported case of Ballantyne syndrome with a large
      placental chorioangioma was successfully alleviated by delivery of the fetus,
      placenta, and tumor. A common denominator among the Ballantyne syndrome and its
      associated pathologic features has not been elucidated.

PMID- 7503219
TI  - Malignant myxoid sarcoma of the Bartholin gland in pregnancy.
AB  - A case of myxoid sarcoma of the Bartholin gland occurring during pregnancy is
      reported. This neoplasm possessed pathologic features consistent with a high
      grade malignancy. The patient underwent a wide reexcision of the clinically
      negative operative site 8 weeks post partum, and no residual evidence of sarcoma
      was identified. In spite of this, a local recurrence occurred 10 months later.
      This was reexcised, and localized electron beam teletherapy was administered.

PMID- 7503220
TI  - Reports on the clinical use of fetal biophysical testing: shouldn't they take
      into consideration the important results from the studies on validity and
      efficacy?

PMID- 7503221
TI  - Hysteroscopy as gold standard for evaluation of abnormal uterine bleeding.

PMID- 7503222
TI  - Neurobiology of uterine irritability in preterm labor.

PMID- 7503223
TI  - No more radiogenic castration in women with Hodgkin's disease?

PMID- 7503224
TI  - Can the risk for Down syndrome be reliably modified by second-trimester
      ultrasonography?

PMID- 7503225
TI  - Spontaneous hair hyperpigmentation in response to vitamin intake in pregnancy--a
      clue for homocystinuria.

PMID- 7503226
TI  - Transgenic animal models of renal development and pathogenesis.
AB  - The use of transgenic animals represents a powerful tool with which to address
      the role of particular gene products in vivo. Recent technical and biological
      advances have simplified the process of creating both transgenic mice and null
      mutation mice. Increasing numbers of genetic control elements are available to
      direct transgene expression to particular renal cell types and to enhance the
      consistency of expression. These approaches have contributed significantly to our
      understanding of renal development and pathogenesis, in particular in the
      following areas: the roles of various oncogenes, homeobox genes, and growth
      factors in renal development and the pathogenesis of cystic renal diseases; the
      contribution of systemic and local expression of the renin-angiotensin system to
      blood pressure control; the role of growth factors and cytokines in progressive
      glomerular disease; the role of viral proteins in the pathogenesis of glomerular
      and tubular disease; and mechanisms of immune-mediated renal disease.

PMID- 7503227
TI  - Cl- channels in basolateral renal medullary vesicles. IX. Channels from mouse
      MTAL cell patches and medullary vesicles.
AB  - The experiments reported herein compared Cl- channels fused into bilayers from
      rabbit outer medullary vesicles with Cl- channels in excised patches of
      basolateral membranes from cultured mouse medullary thick ascending limb (MTAL)
      cells and evaluated whether the latter were plausible candidates for the Cl-
      channels mediating net NaCl absorption in microperfused mouse MTAL segments. The
      unique signature characteristics of Cl- channels incorporated into lipid bilayers
      from outer medullary vesicles include activation of open probability (Po) by
      increases in the Cl- concentrations bathing intracellular faces; activation of Po
      by protein kinase A (PKA) + ATP, when the Cl- concentrations bathing
      intracellular faces are low; and no effect of PKA + ATP on Po with high
      cytoplasmic-face Cl- concentrations. These same properties were observed in Cl-
      channels studied using excised patches of basolateral membranes from mouse MTAL
      cells. Moreover, in both bilayers and in excised patches, the sharpest fractional
      increase in Cl- channel Po occurred with cytosolic-face Cl- concentration
      increases to values similar to the antidiuretic hormone (ADH)-dependent values of
      intracellular Cl- activity in microperfused mouse MTAL segments, and these
      fractional Po increases were adequate to account quantitatively for the ADH
      dependent increase in basolateral membrane Cl- conductance in microperfused mouse
      MTAL segments. Thus the excised-patch basolateral Cl- channels reported here are
      reasonable candidates for those mediating net Cl- absorption in the MTAL.

PMID- 7503228
TI  - Cross-linked hemoglobin increases fractional reabsorption and GFR in hypoxic
      isolated perfused rat kidneys.
AB  - We compared the ability of human red blood cells (RBC) and a cell-free oxygen
      carrier to maintain isolated perfused kidney function under moderately hypoxic
      conditions. Recirculating perfusate was gassed initially with 93% air-7% CO2,
      and, after 30 min, the gas was changed to 12 O2-7 CO2-81% N2. Oxygen content of
      the perfusate was increased with RBC (30 g/l Hbg) or highly purified human
      hemoglobin Ao (HbAo) polymerized with O-raffinose (o-R-poly-Hb, 30 g/l Hbg). For
      comparison, kidneys were perfused with 60 g/l of bovine serum albumin (BSA)
      alone. The effects of unmodified hemoglobin were examined by adding 5 g/l of
      nonpolymerized HbAo to the BSA perfusate after 20 min. The effect of increasing
      oxygen delivery without hemoglobin was examined by switching to 93% O2 after 20
      min during some BSA perfusions (BSA-HiO2). Vascular resistance decreased
      progressively in o-R-poly-Hb- and BSA-HiO2-perfused kidneys but remained constant
      in other experiments. Nitro-L-arginine methyl ester (L-NAME) prevented
      vasodilation and increased the filtration fraction of o-R-poly-Hb-perfused
      kidneys with no change in other functions. L-NAME also prevented the formation of
      methemoglobin. After a 70-min perfusion with BSA, Na reabsorption was 82 +/- 3%
      (means +/- SD), and inulin clearance [glomerular filtration rate (GFR)] was 0.66
      +/- 0.33 ml.min-1.g-1. RBC increased reabsorption to 95% (85-98%) (median, 25th
      75th percentile) but did not alter GFR (0.52 +/- 0.26 ml.min-1.g-1). o-R-poly-Hb
      increased Na reabsorption proportionately more than GFR, so that, while GFR was
      doubled to 1.04 +/- 0.40 ml.min-1.g-1, Na reabsorption increased to 98% (92
      99.5%). HbAo increased GFR to 1.07 +/- 0.44 ml.min-1.g-1 and increased
      reabsorption to 89 +/- 6%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503229
TI  - Actin filaments stimulate the Na(+)-K(+)-ATPase.
AB  - In this report, the functional role of actin on Na(+)-K(+)
      adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity was explored. The Na(+)- and
      K(+)-dependent, ouabain-sensitive ATP hydrolysis mediated by rat kidney Na(+)
      K(+)-ATPase increased by 74% in the presence of previously unpolymerized actin
      (24 microM), whereas addition of polymerized actin was without effect. Addition
      of actin was associated instead with an increase in the affinity of the Na(+)
      K(+)-ATPase for Na+ but not other enzymatic substates. A maximal stimulatory
      effect (296%) was observed either at an Na(+)-K(+)-ATPase:actin ratio of 1:50,000
      or at lower ratios (1:625) by shifting from the E2 (K+ selective) to the E1 (Na+
      selective) conformation of the enzyme. Immunoblotting of actin to the purified
      Na(+)-K(+)-ATPase suggested that this interaction may be linked to binding of
      actin to the enzyme, which was further supported by sequence analysis indicating
      putative actin-binding domains in the alpha-subunit of the enzyme. The
      interaction between actin and the Na(+)-K(+)-ATPase may imply a novel functional
      role of the cytoskeleton in the control of ion transport.

PMID- 7503230
TI  - Angiotensin IV receptors and signaling in opossum kidney cells.
AB  - The pharmacological properties and signaling of angiotensin IV (ANG IV) receptors
      were studied in opossum kidney cell line OK7A. Saturation binding experiments
      with 125I-labeled ANG IV demonstrated the presence of high-affinity ANG IV
      binding sites in OK7A cell membranes with a dissociation constant (Kd) of 0.40 +/
      0.08 nM and a maximal amount of binding sites (Bmax) of 180 +/- 50 fmol/mg
      protein. In competition experiments, unlabeled ANG IV inhibited 125I-ANG IV
      binding biphasically: 20% of binding sites had high affinity [inhibition constant
      (Ki) = 0.44 +/- 0.04 nM] and 80% had low affinity (Ki = 130 +/- 10 nM). ANG III
      displaced 125I-ANG IV from binding sites with low affinity (Ki = 205 +/- 10 nM),
      and ANG II did not compete with 125I-ANG IV at concentrations up to 10 microM.
      The binding of ANG IV to OK7A cell membranes was significantly enhanced in the
      presence of 5 mM EDTA and completely blocked by 5 mM dithiothreitol. Guanosine 5'
      O-(3-thiotriphosphate) inhibited the binding of 125I-ANG IV, indicating the G
      protein coupling of ANG IV receptors in OK7A cells. In signaling studies, ANG IV
      induced transient increase in intracellular calcium concentration ([Ca2+]i) from
      49 +/- 3 to 280 +/- 45 nM. ANG IV failed to influence phosphoinositol metabolism,
      indicating that Ca2+ mobilization is not linked to ANG IV signaling. Ethylene
      glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid completely abolished
      ANG IV-induced increase in [Ca2+]i, consistent with Ca2+ influx. The voltage
      sensitive Ca2+ channel blocking agents verapamil and nifedipine attenuated the
      effect of ANG IV on [Ca2+]i to 133 +/- 33 and 174 +/- 32 nM, respectively. These
      data suggest that ANG IV induces Ca2+ influx in OK7A cells, at least partially,
      through the voltage-sensitive Ca2+ channels.

PMID- 7503231
TI  - FGF-1 in normal and regenerating kidney: expression in mononuclear, interstitial,
      and regenerating epithelial cells.
AB  - The proximal tubule epithelium regenerates following nephrotoxic damage. To
      determine the role of fibroblast growth factors (FGFs) in the regeneration of rat
      proximal tubule epithelial (RPTE) cells, we investigated proliferation,
      differentiation, and FGF-1 expression in vivo in rat kidney before and after
      nephrotoxic damage to the proximal tubule epithelium caused by S-(1,1,2,2
      tetrafluoroethyl)-L-cysteine administration. In undamaged kidneys, FGF-1 was
      expressed in distal tubule elements, including cortical and medullary collecting
      ducts, as well as in blood vessels and glomeruli, but was absent in RPTE. One day
      after damage, there was an increase in proliferation of surviving proximal tubule
      epithelial cells and a coincident increase in FGF-1 expression in invading
      mononuclear cells. After this initial burst of proliferation, FGF-1 expression
      increased in poorly differentiated vimentin-positive regenerative epithelial
      cells, indicating that autocrine FGF-1 expression in the regenerative epithelium
      is a later event in the regeneration process. FGF-1 staining persisted in foci of
      macrophages, interstitial cells, and nephropathic tubules within areas of
      interstitial expansion 2 wk after damage. We concluded that transient paracrine
      and autocrine expression of FGF-1 could play mitogenic and/or morphogenic roles
      during tubular regeneration. Persistent expression in macrophages, fibroblasts,
      and nephropathic tubules may be associated with tubular degeneration. FGF-1
      expression may be an important contributor to both tubular regeneration and
      degenerative disease following toxicant exposure.

PMID- 7503232
TI  - Aquaporin-3 water channel localization and regulation in rat kidney.
AB  - The aquaporins are a family of water channels expressed in several water
      transporting tissues, including the kidney. We have used a peptide-derived,
      affinity-purified polyclonal antibody to aquaporin-3 (AQP-3) to investigate its
      localization and regulation in the kidney. Immunoblotting experiments showed
      expression in both renal cortex and medulla, with greatest expression in the base
      of the inner medulla. Subcellular fractionation of membranes, using progressively
      higher centrifugation speeds, revealed that AQP-3 is present predominantly in the
      4,000 and 17,000 g pellets and, in contrast to AQP-2, is virtually absent in the
      high-speed (200,000 g) pellet that contains small intracellular vesicles.
      Immunocytochemistry and immunofluorescence studies revealed that labeling is
      restricted to the cortical, outer medullary, and inner medullary collecting
      ducts. Within the collecting duct, principal cells were labeled, whereas
      intercalated cells were unlabeled. Consistent with previous immunofluorescence
      studies (K. Ishibashi, S. Sasaki, K. Fushimi, S. Uchida, M. Kuwahara, H. Saito,
      T. Furukawa, K. Nakajima, Y. Yamaguchi, T. Gojobori, and F. Marumo. Proc. Natl.
      Acad. Sci. USA 91: 6269-6273, 1994; T. Ma, A. Frigeri, H. Hasegawa, and A. S.
      Verkman. J. Biol. Chem. 269: 21845-21849, 1994), the labeling was confined to the
      basolateral domain. Immunoelectron microscopy, using the immunogold technique in
      ultrathin cryosections, demonstrated a predominant labeling of the basolateral
      plasma membranes. In contrast to previous findings with AQP-2, there was only
      limited AQP-3 labeling of intracellular vesicles, suggesting that this water
      channel is not regulated acutely through vesicular trafficking. Immunoblotting
      studies revealed that thirsting of rats for 48 h approximately doubled the amount
      of AQP-3 protein in the inner medulla. These studies are consistent with a role
      for AQP-3 in osmotically driven water absorption across the collecting duct
      epithelium and suggest that the expression of AQP-3 is regulated on a long-term
      basis.

PMID- 7503234
TI  - Unique localization of mRNA encoding plasma membrane Ca2+ pump isoform 3 in rat
      thin descending loop of Henle.
AB  - In our previous study of plasma membrane Ca2+ pump (PMCA) isozymes in the rat
      kidney, we found that the mRNA coding isoform PMCA3 was detected primarily in the
      outer medullary zone of rat kidney tissue. We now investigated the location of
      the mRNAs coding for isoforms PMCA3 and PMCA4 of Ca2+ pump in the nephron
      segments that are present in outer medullary parenchyma using the method of
      reverse transcription and polymerase chain reaction. In mRNA extracted from whole
      dissected outer medulla we detected mRNA encoding three splice variants (a, b,
      and c) of isoform PMCA3; isoform PMCA4 was found in the outer medulla almost
      exclusively as variant b. Analysis of mRNA from microdissected tubule segments
      show that proximal straight tubules (PST), medullary thick ascending limbs, outer
      medullary collecting ducts, and descending thin limb of Henle's loop (DTL) all
      contained mRNA for isoform 4b. In contrast, the mRNA encoding isoform 3 was
      detected exclusively in DTL and not in other nephron segments. The unique
      presence of isoform 3 in DTL is rather surprising, since the specific role of
      this nephron segment in vectorial Ca2+ transport or in intracellular Ca2+
      signaling is not known. The data suggest that isoform 3 in cells of the DTL may
      have a hitherto unrecognized specific role in Ca2+ signaling or transport of
      Ca2+, which is distinct from the role of the isoforms of the PMCA in all other
      nephron segments.

PMID- 7503233
TI  - Protein phosphatase-1 in the kidney: evidence for a role in the regulation of
      medullary Na(+)-K(+)-ATPase.
AB  - Previous studies of hormonal regulation of renal Na(+)-K(+)-ATPase have indicated
      that the activity of the sodium pump is regulated by phosphorylation
      dephosphorylation reactions. Here we report that okadaic acid (OA) and calyculin
      A (CL-A), inhibitors of protein phosphatase (PP)-1 and PP-2A, inhibited Na(+)
      K(+)-ATPase activity in cells from the rat thick ascending limb (TAL) of loop of
      Henle in a dose-dependent manner. CL-A was 10-fold more potent than OA. On the
      basis of the inhibitory constant values of CL-A and OA for PP-1 and PP-2A, it is
      concluded that the tubular effect is mainly due to inhibition of PP-1. In situ
      hybridization studies with oligonucleotide probes revealed very strong PP-1 alpha
      and PP-1 gamma 1 mRNA labeling in the outer stripe of the outer medulla, strong
      labeling in the inner stripe of the outer medulla, and weak labeling in the inner
      medulla. Very weak labeling was demonstrated in the outer cortex. PP-1 beta mRNA
      labeling was very strong in the inner stripe of the outer medulla, whereas the
      outer stripe had weaker labeling, and the inner medulla had weak labeling. PP-1
      alpha, PP-1 beta, and PP-1 gamma 1 mRNA were also demonstrated in the
      transitional epithelium of the ureter. The abundance of the PP-1 alpha and PP-1
      gamma isoforms as measured by immunoblotting was very high in tissue from the
      outer medulla, which also has a high abundance of the endogenous dopamine
      regulated PP-1 inhibitor, DARPP-32.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503236
TI  - Renal inner medullary sorbitol metabolism.
AB  - Sorbitol participates in the osmoregulation of several renal cells and has also
      been found in isolated inner medullary collecting duct (IMCD) cells in primary
      culture. Therefore, osmotic regulation and distribution of sorbitol and the key
      enzymes of sorbitol metabolism, aldose reductase and sorbitol dehydrogenase in
      the renal inner medulla, were investigated in vivo under various osmotic
      conditions (control, diuresis, antidiuresis). In homogenates of the renal inner
      medulla of Wistar rats, the sorbitol content correlated with the urine osmolarity
      [68 +/- 12 mumol/g protein (control), 28 +/- 9 mumol/g (diuresis), 110 +/- 15
      mumol/g (antidiuresis)]. Similar results were obtained for the activity of aldose
      reductase (sorbitol synthesis) [25 +/- 4 U/g (control), 19 +/- 3 U/g (diuresis),
      and 48 +/- 7 U/g (antidiuresis)]. On the contrary, the activity of sorbitol
      dehydrogenase (sorbitol degradation) was significantly increased to 1.26 +/- 0.42
      U/g under diuretic conditions vs. control (0.84 +/- 0.14 U/g, P < 0.05). These
      results demonstrate the correlation between the enzymes of sorbitol synthesis and
      sorbitol degradation in the intact inner medulla and the urine osmolarity in
      vivo. Whereas the aldose reductase activity was 2.3-fold enriched in IMCD cells,
      the specific activity of sorbitol dehydrogenase was relatively increased in a
      preparation of enriched interstitial cells. This distribution was not dependent
      on the various diuretic conditions. These results indicate that enzymes of
      synthesis and of degradation of sorbitol are osmotically regulated in vivo.
      Therefore, the enzymatic activities of sorbitol synthesis appear to be primarily
      located in epithelial cells, whereas enzymatic activities of sorbitol degradation
      seem to be localized in interstitial cells of the renal inner medulla.

PMID- 7503235
TI  - Developmental regulation of chloride/formate exchange in guinea pig proximal
      tubules.
AB  - There is a marked decrease in renal NaCl excretion immediately following birth.
      To test the hypothesis that parallel upregulation of the proximal tubule apical
      membrane Na+/H+ and Cl-/formate exchangers contributes to this postnatal
      adaptation, we measured exchanger activities in brush-border membrane vesicles
      from near-term fetal, 3- to 5-day-old, and adult guinea pigs. Uptake of 36Cl- was
      measured in the presence of an outwardly directed formate gradient and an
      inwardly directed proton gradient. In other experiments, 22Na+ uptake was
      measured in the presence of an outwardly directed proton gradient. 36Cl- uptake
      was inhibitable by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and
      furosemide, and 22Na+ uptake was inhibitable by amiloride. Maximal uptakes of
      both 36Cl- and 22Na+ exceeded 2-h equilibration values in vesicles from newborn
      and adult guinea pigs, suggesting transporter-mediated uptake. Such overshoots
      were not seen with the vesicles from fetuses. Compared with vesicles from
      fetuses, the initial velocity of formate-driven 36Cl- uptake was 73% greater in
      vesicles from newborns and 65% greater in vesicles from adults. These results
      demonstrate parallel upregulation of proximal tubule Na+/H+ and Cl-/formate
      exchanger activities immediately after birth. This parallel upregulation may be
      important in mediating the postnatal decrease in renal NaCl excretion.

PMID- 7503237
TI  - Quantitative RT-PCR analysis of calcitonin receptor mRNAs in the rat nephron.
AB  - A quantitative assay based on the method of reverse transcription and polymerase
      chain reaction (RT-PCR) was developed to study the expression of calcitonin (CT)
      receptors in microdissected rat nephron segments. Steady-state mRNA levels of two
      CT-receptor spliced variants (CT1a and CT1b) were measured using a mutant cRNA as
      internal standard. CT1a, but not the CT1b isoform, was detected in the kidney
      cortex, outer medulla, and papilla. Among the tested segments, predominant
      expression of CT1a mRNA was found in the cortical thick ascending limb of Henle's
      loop (754 +/- 87 mRNA molecules/mm tubular length; n = 8). Lower expression
      levels were measured in the medullary thick ascending limb (460 +/- 62
      molecules/mm tubule length; n = 7) and in the cortical collecting duct (327 +/-
      61 molecules/mm tubule length; n = 6). A weak expression was also detected in the
      outer medullary collecting duct and the glomerulus. No expression was found in
      the proximal convoluted tubule, pars recta, and thin descending and thin
      ascending limb of Henle's loop. We conclude that only the CT1a-receptor mRNA is
      present in the rat kidney, with a significant level of expression in the cortical
      and medullary thick ascending limb and in the cortical collecting duct.

PMID- 7503238
TI  - Kallikrein excretion in Dahl salt-sensitive and salt-resistant rats with native
      and transplanted kidneys.
AB  - Urinary kallikrein excretion is decreased in Dahl salt-sensitive (S) vs. salt
      resistant (R) rats, and several lines of reasoning suggest not only that
      decreased kallikrein excretion is a marker for salt-sensitive hypertension but
      also that kallikrein might play a pathogenic role. Because previous cross
      transplantation studies have demonstrated that the kidney's genotype plays a role
      in determining the blood pressure of the recipient in Dahl S and R rats, the
      present experiments were designed to determine whether both blood pressure and
      urinary kallikrein excretion "traveled with the kidney" in transplantation. The
      Rapp strains of S and R were maintained on a low- NaCl (0.13%) diet until kidney
      transplantation (bilaterally nephrectomized recipients), at which time the diet
      was switched to high NaCl (7.8%). Sixteen days later, blood pressures (tail-cuff
      plethysmography) of the cross-transplant groups (R/S and S/R, indicating kidney
      genotype/recipient genotype) were nearly identical to each other and intermediate
      between the blood pressures of the control groups with transplanted kidneys (R/R
      and S/S). Renal function studies, performed on anesthetized rats 17 days after
      surgery, demonstrated that R kidneys had higher glomerular filtration rates,
      renal plasma flows, and urinary kallikrein excretion rates than S kidneys. These
      differences tended to be preserved in the cross-transplant groups, and therefore
      they must be genetically determined intrinsic differences between R and S
      kidneys. This was especially striking with respect to urinary kallikrein
      excretion. The rank order of urinary kallikrein excretion was R/R = R/S > S/R =
      S/S, which implies that it is completely determined by the genotype of the
      kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503240
TI  - Regulation of luminal alkalinization and acidification in the cortical collecting
      duct by angiotensin II.
AB  - Angiotensin II (ANG II) regulates whole kidney ion transport, yet its effects in
      the collecting duct are unknown. The purpose of these studies was to determine
      whether ANG II regulates luminal alkalinization and acidification in the rabbit
      cortical collecting duct (CCD). The rate of luminal alkalinization or
      acidification was measured as the rate of change of luminal fluid pH under stop
      flow conditions using in vitro microperfused CCD segments. Outer CCD alkalinized
      the luminal fluid, consistent with net HCO3- secretion. Addition of ANG II, 10(
      7) M, to the peritubular solution for 30 min significantly stimulated luminal
      alkalinization. The stimulatory effect of ANG II was not due to time-dependent
      effects and was blocked by peritubular addition of the ANG II type 1 (AT1)
      receptor antagonist, losartan, at 10(-6) M. Losartan, 10(-6) M, when added to the
      peritubular solution, did not alter the rate of luminal alkalinization
      independent of ANG II. In contrast, peritubular ANG II, 10(-7) M, did not alter
      inner CCD luminal acidification. Addition of ANG II to the peritubular solution
      at the lower concentration of 10(-10) M did not alter the rates of luminal
      alkalinization and acidification in the outer and inner CCD, respectively.
      Peritubular ANG II, 10(-7) M, but not vehicle, stimulated B cell apical HCO3-
      secretion occurring in response to peritubular Cl- removal. These studies
      demonstrate that ANG II acts through a basolateral AT1 receptor to stimulate
      outer CCD luminal alkalinization via, at least in part, B cell stimulation.

PMID- 7503239
TI  - Role of NF-kappa B in the regulation of inducible nitric oxide synthase in an
      MTAL cell line.
AB  - The effects of cytokines, lipopolysaccharide (LPS), 8-bromoadenosine 3',5'-cyclic
      monophosphate (8-BrcAMP), and pyrrolidine dithiocarbamate (PDTC), an inhibitor of
      nuclear factor kappa B (NF-kappa B) activation, on inducible nitric oxide
      synthase (iNOS) expression were studied in the medullary thick ascending limb of
      Henle's loop cell line ST-1. LPS + interferon-gamma (IF-gamma) promoted a time
      dependent increase in nitrite (a NO metabolite) and iNOS mRNA and the appearance
      of NF-kappa B p50 and p65 in nuclear protein extracts. Actinomycin D but not
      cycloheximide prevented the LPS + IF-gamma induction of iNOS mRNA and NO
      synthesis, indicating that iNOS transcriptional activation by LPS + IF-gamma does
      not require newly synthesized proteins. PDTC inhibited the LPS + IF-gamma
      induction of NO, iNOS mRNA, and the appearance of NF-kappa B in nuclear protein
      extracts, suggesting that NF-kappa B mobilization and trans-activation of the
      iNOS gene mediates this induction. In contrast to other cell types, cycloheximide
      did not alter iNOS mRNA stability, and 8-BrcAMP did not alter basal or LPS+IF
      gamma induced NO production in ST-1 cells.

PMID- 7503241
TI  - Complement C5b-9 activates cytosolic phospholipase A2 in glomerular epithelial
      cells.
AB  - In rat membranous nephropathy, complement C5b-9 induces glomerular epithelial
      cell (GEC) injury and proteinuria, which, in some models, is partially mediated
      by eicosanoids. By analogy, sublytic C5b-9 injures plasma membranes and releases
      arachidonic acid (AA) and eicosanoids in cultured rat GEC. In this study, we
      demonstrate that, in GEC, sublytic C5b-9 stably increased the activity of a high
      molecular-mass cytosolic phospholipase A2 (PLA2), which we identified as "cPLA2."
      This increase was abolished with inhibitors of protein kinase C. C5b-9 did not
      affect low-molecular-mass membrane-associated or secretory PLA2 activities. In
      GEC that stably overexpress cPLA2 activity and protein (produced by transfection
      of cPLA2 cDNA), immunoblot analysis showed that sublytic C5b-9 induced a
      decreased mobility of cPLA2, consistent with cPLA2 phosphorylation. Incubation of
      cPLA2-transfected GEC with sublytic C5b-9 significantly increased production of
      free AA and prostaglandin E2, whereas, in control GEC, the C5b-9-induced changes
      in free AA and prostaglandin E2 were small. Furthermore, both C5b-9-dependent
      sublytic cytotoxicity and cytolysis were enhanced in GEC overexpressing cPLA2,
      compared with control cells. Thus C5b-9 increased cPLA2 activity, probably via
      phosphorylation involving a protein kinase C-dependent pathway. Phospholipid
      hydrolysis by cPLA2 resulted in release of substrate for eicosanoid synthesis and
      in enhancement of C5b-9-dependent GEC injury. Both processes may facilitate
      glomerular damage in membranous nephropathy.

PMID- 7503242
TI  - Development and prevention of skeletal muscle structural alterations after
      experimental myocardial infarction.
AB  - The present study was designed to assess whether structural alterations develop
      within skeletal muscle 1 yr after myocardial infarction (MI) and failure and, if
      so, whether these structural alterations can be prevented by angiotensin
      converting enzyme (ACE) inhibition. Infarcted rats were randomized and treated
      for 1 yr with either placebo (MI-IP, n = 9), a low dose of lisinopril (MI-LL, 0.5
      mg.kg-1.day-1, n = 12), or a high dose of lisinopril (MI-LH, 5 mg.kg-1.day-1, n =
      9). Sham-operated animals served as controls (SH, n = 14). One year after MI, in
      situ fixation of rat hindlimb was performed to investigate interstitial collagen
      volume fraction (CVF), capillary density, and media thickness of resistance
      vessels (80-200 microns) of musculus quadriceps femoris muscle. Infarct size was
      similar in all infarct groups and averaged 26 +/- 4%. Right ventricular weight
      was increased in MI-IP compared with SH, MI-LL, and MI-LH. Both left ventricular
      (LV) CVF and skeletal muscle CVF were increased in MI-IP. LV CVF and skeletal
      muscle CVF were closely related to each other (n = 44, r = 0.5377, P < 0.002). In
      infarcted rats, high-dose ACE inhibition significantly reduced skeletal muscle
      and LV CVF. Skeletal muscle capillary density and capillary-to-muscle fiber ratio
      were significantly decreased in infarcted rats but were restored by low- and high
      dose ACE inhibition. Media thickness of intramuscular resistance vessels was
      increased in the MI-IP group and significantly reduced by high-dose ACE
      inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503243
TI  - Albumin reduces basement membrane hydraulic conductance in part due to arginyl
      side groups.
AB  - Albumin reduces capillary hydraulic conductance (Lp) even at low concentrations.
      To determine if part of this barrier protective effect might be extracellular, we
      studied the effects of bovine serum albumin (BSA) on Lp of self-assembled
      basement membrane (Matrigel). Lp with tris(hydroxymethyl)aminomethane (Tris)
      buffer superfusate was stable at 1.77 +/- 0.22 x 10(-5) (SE) cm.s-1.cmH2O-1 over
      several hours. At 0.1 g/dl BSA, experimental/control (Tris) Lp fell to 83.1 +/-
      6.0% (2P < 0.025), with decreases to 72.4 +/- 3.7% at 1 g/dl (2P < 0.005), 45.3
      +/- 5.1% at 2.5 g/dl (2P < 0.001), and 45.0 +/- 4.8% at 4.0 g/dl (2P < 0.001). In
      separate experiments, BSA arginine groups were neutralized by 1,2
      cyclohexanedione (CHD), and experimental/control Lp values were measured. At 2.5
      g/dl, CHD-BSA depressed Lp to 54.4 +/- 4.8%, while unmodified BSA reduced Lp to
      40.8 +/- 3.5% of Tris control (2P = 0.05). Finally, soluble arginine at three-
      and sixfold the arginine in BSA was added to BSA superfusate. For threefold, Lp
      rose to 120 +/- 8% of BSA level and for sixfold to 129 +/- 9% (2P < 0.05). We
      conclude that some part of the albumin protective effect is very likely due to
      consequences on extracellular matrix and that at least 18-22% of this effect is
      related to arginine groups on albumin when computed from Lp, and up to 34% when
      viscosity is taken into account. Membrane-saturable arginine-binding sites can be
      unbound with arginine, thus nullifying part of the barrier protective effect of
      BSA.

PMID- 7503244
TI  - Response of cerebral blood vessels to an endogenous inhibitor of nitric oxide
      synthase.
AB  - We examined effects of NG,NG-dimethyl-L-arginine (asymmetric dimethylarginine,
      ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, on cerebral
      vascular responses using cranial windows in anesthetized rats and rabbits. Under
      control conditions in rats, topical application of 10 and 100 microM ADMA
      constricted the basilar artery by 9 +/- 2 and 19 +/- 1% (SE; P < 0.05, n = 8),
      respectively, from a baseline diameter of 213 +/- 19 microns. ADMA (10 and 100
      microM) produced marked inhibition of vasodilation in response to acetylcholine
      without inhibiting vasodilatation in response to nitroprusside. ADMA (1-100
      microM) inhibited activity of brain NO synthase (measured as the conversion of L
      [14C]arginine to L-[14C]citrulline). In cerebrum and cerebellum, 50% inhibition
      of activity of NO synthase was produced by 2.3 +/- 0.4 and 1.8 +/- 0.1 microM
      ADMA, respectively. In rabbits, treatment with ADMA (300 microM) decreased
      baseline diameter of cerebral arterioles (control diameter = 93 +/- 10 microns)
      by 11 +/- 2% (P < 0.05, n = 10). In response to 1 microM acetylcholine, cerebral
      arterioles dilated by 36 +/- 6 and 13 +/- 4% (P < 0.05 vs. control) in the
      absence and presence of ADMA, respectively. Effects of ADMA were prevented by L
      arginine. Thus ADMA inhibits activity of brain NO synthase and relaxation of
      cerebral blood vessels in response to acetylcholine. Because ADMA is produced in
      relatively high concentrations in brain, it may be an important endogenous
      modulator of cerebral vascular tone under resting conditions and in response to
      vasoactive stimuli.

PMID- 7503245
TI  - Changes in endothelial actin cytoskeleton in venules with time after histamine
      treatment.
AB  - In this study the time course of development and recovery of histamine-induced
      venular leaks was followed in conjunction with rearrangement of endothelial actin
      fibers. The microvasculature of a single mesenteric window of anesthetized
      Sprague-Dawley rats was perfused with buffered saline, with or without 10(-4) M
      histamine, for 3-30 min. Fluorescein isothiocyanate (FITC)-albumin was added for
      the last 3 min. The microvasculature was perfusion fixed, stained with rhodamine
      phalloidin (for filamentous actin), and viewed using confocal microscopy. The
      number and relative size of FITC-albumin leaks per venule length were measured.
      After 3 min of histamine application focal leaks appeared in some of the venules.
      Most focal leaks were accompanied by local breaks in the endothelial peripheral
      actin rim. Larger leaks were also present, accompanied by greater disruption of
      the venular endothelial peripheral actin rim, diffuse F-actin staining, and
      adherent platelets and leukocytes. Few central actin fibers were visible even in
      endothelial cells associated with large leaks. After 10-15 min of histamine
      exposure, larger leaks were more abundant but with fewer adherent cells. Central
      actin fibers in endothelial cells increased in number, peaking after 20 min of
      histamine, while the diffuse actin staining declined. Leak area per micrometer of
      venule peaked at 10-15 min, but the numbers of leaks per micrometer did not vary
      significantly from 3 to 30 min. These data suggest that the central fibers are
      not involved with the phase of increasing permeability, but they may play a role
      in the structural and functional recovery of endothelial cells perturbed by
      histamine.

PMID- 7503246
TI  - Endothelial inhibition of myofilament calcium response in intact cardiac
      myocytes.
AB  - Recent studies suggest that factors released by endothelial cells can modify
      contraction of isolated cardiac preparations. We compared the effects of 1)
      coronary effluent collected from Langendorff-perfused rat hearts and 2) cultured
      vascular endothelial cell superfusate on isolated fura 2-loaded rat ventricular
      cardiac myocytes. Coronary and cultured cell effluent produced similar effects.
      Isotonic contraction amplitude was reduced by 31.6 +/- 2.6 and 70.2 +/- 9.1%,
      respectively; myocyte diastolic length increased by 0.8 +/- 0.2 and 1.5 +/- 0.4
      microns, and time to 50% relaxation fell by 6.2 +/- 1.8 and 10.1 +/- 2.0% (all P
      < 0.05; n = 29 and 15 myocytes, respectively). A small fall in the amplitude of
      the intracellular Ca2+ transient was observed (8.5 +/- 1.5 and 10.9 +/- 3.5%,
      respectively; both P < 0.01), insufficient to account for the reduction in twitch
      amplitude. In intact myocytes tetanized in the presence of thapsigargin, the
      steady-state myofilament response to Ca2+ was reduced by coronary and cultured
      cell effluent. These results suggest that both coronary endothelial cells in situ
      and cultured endothelial cells tonically release a factor(s) that reduces
      myofilament Ca2+ response.

PMID- 7503247
TI  - High muscle blood flows are not attenuated by recruitment of additional muscle
      mass.
AB  - Recent studies have demonstrated that single-leg knee extensor (KE) exercise
      elicits high mass-specific blood flow (Q) which, if incremented toward maximum,
      in the presence of additional muscle recruitment would soon outstrip the heart's
      pumping capacity and blood pressure would fall. Thus incremental KE exercise
      provides the opportunity to determine the intensity at which, if at all,
      quadriceps muscle hemodynamics are altered during incremental exercise that
      involves a substantially greater muscle mass. Leg Q was measured during
      incremental KE exercise and again with superimposed incremental two-legged knee
      extensor exercise with incremental arm cranking (A+L) in trained subjects (n =
      5). Leg Q and vascular conductance (VC) increased with work rate (WR) to reach
      high levels [Q = 385.7 +/- 26 and 342.3 +/- 15 ml.min-1.100 g-1 for KE and A+L
      exercise, respectively; VC at 90% of maximum WR (WRmax) = 79 +/- 5 and 75 +/- 6
      ml.min-1. mmHg-1 for KE and A+L exercise, respectively], but the Q/WR and VC/WR
      relationships in KE and A+L exercise were not different. Maximum O2 consumption
      (VO2max) and the VO2max/WR relationship of the quadriceps were also unaffected by
      the additional muscle mass recruited. Despite a significantly greater net femoral
      venous norepinephrine (NE) outflow at both 90 and 100% of WRmax in A+L exercise
      (WRmax = 4,216 +/- 1,601 and 901 +/- 99 ng/ml for A+L and KE exercise,
      respectively; P < 0.05), leg Q continued to rise linearly with WR.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7503248
TI  - Inotropic effects of alpha 1-adrenergic agonists in myocardium from rats with
      postinfarction heart failure.
AB  - In clinical and experimental heart failure, the inotropic response to beta
      adrenergic receptor stimulation is depressed. Therefore, non-beta-adrenergic
      mechanisms may assume increasing importance for summoning inotropic reserve in
      the failing heart. To test the integrity of the inotropic pathway mediated by
      alpha 1-adrenergic receptor stimulation in a model of chronic ischemic heart
      failure, we administered phenylephrine to noninfarcted left ventricular papillary
      muscles isolated from sham-operated rats (n = 10) and rats with large (> 40% left
      ventricular circumference) anterior myocardial infarctions (n = 9). Isometric
      force was monitored, and intracellular Ca2+ (Cai2+) transients were recorded with
      the bioluminescent protein aequorin. Compared with muscles from sham-operated
      rats, contractility of muscles from rats with postinfarction heart failure was
      depressed at extracellular Ca2+ concentrations between 0.5 and 3.0 mM.
      Phenylephrine produced comparable dose-dependent increases in developed tension
      (126 +/- 4 vs. 125 +/- 7% of baseline) and peak rate of tension rise (125 +/- 4
      vs. 140 +/- 9% of baseline) in muscles from sham and infarcted rats,
      respectively. There was no significant change in the time course of the isometric
      twitch or in the time course or amplitude of the Cai2+ transient after
      phenylephrine administration in muscles from either group. No evidence of Cai2+
      overload, as defined by spontaneous Ca2+ release, was observed during
      phenylephrine administration in muscles from normal or failing hearts. The
      density of alpha 1-adrenoceptors measured with [3H]prazosin binding in crude
      membranes isolated from noninfarcted left ventricular tissue was not different in
      control and infarcted hearts (48 +/- 5 vs. 53 +/- 4 fmol/mg protein). These data
      indicate that the positive inotropic effect of alpha-agonists may be preserved in
      chronic ischemic heart failure. In both normal and failing myocardium, the
      inotropic effects of alpha 1-adrenergic stimulation occurred with little or no
      increase in Cai2+ availability and no apparent adverse effects on myocardial
      relaxation. Therefore, agents that act by similar mechanisms may have certain
      therapeutic advantages over traditional inotropic agents in patients with heart
      failure.

PMID- 7503250
TI  - Reflex control of vasopressin during hemorrhage in hypertensive rabbits.
AB  - Hypertensive (HT) rabbits have impaired reflex control of heart rate and vascular
      tone, which is, at least in part, related to dysfunctional baroreceptors. We
      hypothesized that reflex control of vasopressin (AVP) would also be impaired in
      the HT rabbit. To test this, we compared hemorrhage-induced increases in AVP
      between conscious normotensive (NT) and HT rabbits. The hemorrhage-induced rise
      in AVP was found to be significantly (P < 0.05) attenuated in the HT rabbits. We
      tested a second hypothesis, that the observed impairment was related to arterial
      baroreceptor function, by hemorrhaging the same rabbits after reversible cardiac
      denervation. Under these conditions, only the arterial baroreceptors would be
      expected to contribute to reflex control of AVP. Impairment was still evident
      after cardiac denervation; that is, the hemorrhage-induced rise in AVP was
      significantly (P < 0.01) attenuated in the cardiac-denervated HT rabbits compared
      with NT rabbits. Thus impairment was, at least in part, related to arterial
      baroreceptors. Previously, we showed in NT rabbits that AVP only contributed to
      maintenance of arterial pressure (during hemorrhage), after the autonomic nervous
      system (ANS) had been blocked. Thus, in the present study, we compared the
      maintenance of arterial pressure during hemorrhage between NT and HT rabbits
      after ANS blockade. Blood pressure maintenance was significantly attenuated in
      the HT rabbits (P < 0.05). In addition, for a given fall in pressure,
      significantly less AVP (P < 0.05) was released in the ANS-blocked HT rabbits as
      compared with NT rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503249
TI  - Catecholamine response to chronic ANG II infusion and its role in myocyte and
      coronary vascular damage.
AB  - Acute elevations in circulating angiotensin II (ANG II) are known to increase
      circulating norepinephrine (NE) levels. However, the time course of catecholamine
      release relative to chronic ANG II infusion is not known. Furthermore, it is
      unknown if this ANG II-induced catecholamine release is ANG II type 1 (AT1)
      receptor mediated or whether the increase in serum catecholamines is responsible
      for the myocyte and coronary vascular damage seen within the first 3 days of
      chronic ANG II infusion. Therefore, we examined the influence of chronic ANG II
      stimulation on serum catecholamine levels with and without AT1 blockade and the
      effect of beta-blockade on ANG II-induced myocyte and coronary vascular damage.
      The results indicate that NE release is AT1 mediated, but NE is not significantly
      elevated until day 4 of ANG II infusion after which it remains elevated. beta
      Blockade prevented most ANG II-related myocyte necrosis and coronary vascular
      damage. Therefore, myocyte and coronary vascular damage do not appear to be
      related to increased serum NE levels, but instead may be due to the release of
      neural catecholamines within the heart.

PMID- 7503251
TI  - Regional vascular reserve in canine atria and ventricles during rest and
      exercise.
AB  - Vascular reserve, which defines the capacity for further vasodilation in a given
      physiological or pathological condition, has not been measured in the canine
      atria. This study defines, in normal dogs, the regional vascular reserve
      simultaneously measured in the atria (appendage, nonappendage regions) and in the
      ventricles during rest and two levels of exercise. Blood flow was determined
      using 11.4 +/- 0.1 microns radiolabeled microspheres. Vascular reserve (percent
      for each region) is the ratio of vascular conductance during each condition to
      maximum vascular conductance. Maximum vascular conductance was estimated by
      infusing adenosine intravenously. For a given physiological condition regional
      vascular conductance varied two- to threefold. The vascular reserve of each of
      the regions decreased progressively from rest to mild exercise to moderate
      exercise. Regional vascular reserve for both atria, the right ventricle, and the
      epicardial layer of the left ventricle was essentially uniform for a given
      condition: rest 93 +/- 0.4%, mild exercise 81 +/- 1.2%, and moderate exercise 69
      +/- 1.5%. This similarity in vascular reserve implies that for a given
      physiological condition a common mechanism precisely regulates myocardial
      perfusion in these cardiac regions as a function of the total vasodilator
      capacity.

PMID- 7503252
TI  - Basic fibroblast growth factor increases nitric oxide synthase production in
      bovine endothelial cells.
AB  - Basic fibroblast growth factor (bFGF) and nitric oxide (NO) are expressed by
      endothelial cells (EC) and are involved in regulation of endothelial functions.
      In vivo, bFGF has a hypotensive effect which is mediated, in part, through
      activation of nitric oxide synthase (NOS) and the subsequent generation of NO.
      Thus we hypothesized that regulation of NOS in EC might be modulated by bFGF.
      bFGF treatment of EC in vitro resulted in increased NADPH diaphorase staining, a
      histochemical marker associated with the presence of NOS. Using cGMP generation
      in a reporter cell as a bioassay for NO release, we demonstrated that bFGF
      treatment of EC leads to increased production of biologically active NO.
      Furthermore, bFGF treatment of EC resulted in an increase in cellular content of
      the endothelial form of NOS as shown by Western blot analysis. Finally, Northern
      blot analysis was used to demonstrate that message levels of the constitutive,
      calcium-dependent, endothelial form of NOS is increased in EC by treatment with
      bFGF in vitro. These results suggest that bFGF has potential to regulate vascular
      tone through the modulation of levels of endothelial NOS.

PMID- 7503253
TI  - Role of myosin phosphorylation and [Ca2+]i in myogenic reactivity and arteriolar
      tone.
AB  - The aim of this study was to define the relationship between intraluminal
      pressure, intracellular calcium concentration ([Ca2+]i), and myosin light-chain
      (MLC) phosphorylation in isolated arterioles exhibiting myogenic tone. Cremaster
      muscles were removed from anesthetized rats, and arterioles (approximately 100
      microns diam) were dissected from surrounding tissues and cannulated on glass
      pipettes. Vessels were warmed to 34 degrees C and initially pressurized to 70
      mmHg in the absence of intraluminal flow. For [Ca2+]i measurements, vessels were
      loaded with 5 microM fura 2, and fluorescence emitted by excitation at 340 and
      380 nm was measured. Data were considered in terms of changes in the fluorescence
      ratio (340/380 nm) and collected at steady-state intraluminal pressures between
      30 and 170 mmHg. For measurement of MLC phosphorylation, vessels were frozen in
      acetone-dry ice followed by sonication in homogenizing buffer. Homogenates were
      separated by two-dimensional gel electrophoresis, and proteins were visualized by
      silver staining. MLC phosphorylation was quantitated photodensitometrically, and
      results are expressed as percent total 20-kDa MLC. Increasing intraluminal
      pressure resultedin significant constriction with increased [Ca2+]i and MLC
      phosphorylation. For example, the fluorescence ratio was 0.80 +/- 0.04 at 30 mmHg
      compared with 1.02 +/- 0.05 at 120 mmHg (n = 7 vessels); corresponding MLC
      phosphorylation values were 27.7 +/- 1.6 and 39.6 +/- 3.0% (n = 6). MLC
      phosphorylation in arterioles superfused with 0 mM Ca(2+)-2 mM ethylene glycol
      bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) was 8.5 +/-
      0.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503254
TI  - Role of endogenous opioids and serotonin in the hemodynamic response to
      hemorrhage during hypoxia.
AB  - Previous studies from our laboratory indicate that acute but not chronic hypoxia
      decreases the hemorrhage volume required to elicit reflex hypotension.
      Furthermore, chronically hypoxic animals exhibit an elevated hypotensive
      threshold during both normoxia and hypoxia compared with control animals. Because
      reports suggest that opioid and serotonergic mechanisms may be involved in
      mediating the sympathoinhibition that occurs with hemorrhage, we hypothesized
      that opioid and/or serotonergic systems are stimulated during hemorrhage under
      conditions of acute hypoxia and suppressed after chronic exposure to hypoxia and
      are thus responsible for the altered cardiovascular responses to hemorrhage under
      each condition. Control and chronically hypoxi rats were administered either the
      opioid receptor antagonist naltrexone (1 mg/kg), the selective 5
      hydroxytryptamine receptor subtype 3 (5-HT3) serotonergic receptor antagonist MDL
      72222 (0.5 mg/kg), or their respective vehicles intravenously before hemorrhage
      was initiated during normoxia or hypoxia (FIO2 = 0.12). In control animals,
      pretreatment with naltrexone increased the hemorrhage was initiated volume
      required to achieve hypotension in hypoxic but not normoxic conditions.
      Naltrexone had no effect on hypotensive threshold in chronically hypoxic animals
      under conditions of either normoxia or hypoxia. In addition, MDL-72222 had no
      effect on hypotensive threshold in either control or chronically hypoxic animals
      in either normoxic or hypoxic conditions. We conclude that endogenous opioids may
      contribute to the reflex hypotension that occurs during hypoxic hemorrhage in
      control rats, while no such involvement is evident in chronically hypoxic
      animals. Furthermore, peripheral 5-HT3 receptors are not likely involved in this
      response during either normoxic or hypoxic hemorrhage in control or chronically
      hypoxic rats.

PMID- 7503255
TI  - Reduced threshold for myocardial cell calcium intolerance in the rat heart with
      aging.
AB  - To determine whether advancing age is accompanied by a reduced Ca2+ tolerance, we
      measured Ca(2+)-dependent diastolic pressure, prolonged relaxation and systolic
      functional deterioration, spontaneous sarcoplasmic reticulum (SR)-generated Ca2+
      oscillations [detected as scattered laser light intensity fluctuations (SLIF)],
      aftercontractions, and ventricular fibrillation in isolated, isovolumic,
      atrioventricular-blocked intact hearts from 24- to 26-mo (old) and 6- to 8-mo
      (young) male Wistar rats. In enzymatically isolated single cardiac myocytes, the
      likelihood of the occurrence of spontaneous contractile waves driven by
      spontaneous SR Ca2+ release was also determined. In response to stepwise increase
      in perfusate Ca2+ concentration (Cao), a reduction in the maximum developed
      pressure accompanied by an elevation in end-diastolic pressure and a prolonged
      contraction duration was observed at lower Cao in old vs. young hearts (P < 0.01
      for each parameter). Furthermore, Ca(2+)-dependent ventricular fibrillation
      occurred during pacing in six old but in no young hearts (P < 0.01),
      aftercontractions were observed in seven old vs. one young heart (P < 0.01), and
      SLIF increased to a greater extent in old vs. young hearts. In single cardiac
      myocytes, spontaneous contractile waves occurred more frequently with increasing
      age (P < 0.01). These results indicate that aging is associated with an increased
      likelihood for the occurrence of SR-generated Ca2+ oscillations and functional
      abnormalities that result from these oscillations.

PMID- 7503256
TI  - Permissive role for nitric oxide in active thermoregulatory vasodilation in
      rabbit ear.
AB  - The present study was designed to test the hypothesis that during whole body
      heating (WBH), nitric oxide (NO) synthesized in the endothelium acts
      synergistically with an unknown neurotransmitter to elicit active vasodilation.
      Rabbits were instrumented for the measurement of mean arterial pressure, heart
      rate, and ear blood flow (EBF) (Doppler ultrasound). During WBH, either N omega
      nitro-L-arginine methyl ester (L-NAME, 10-40 mg over 10-15 min, n = 6 rabbits;
      group 1), a NO synthase inhibitor, or saponin (30-40 mg over 10-20 min, n = 6
      rabbits; group 2), a detergent that denudes the endothelium, was given via a
      lingual artery catheter until thermoregulatory vasodilation was reversed. When
      EBF stabilized at the new reduced level, the NO donor, sodium nitroprusside
      (SNP), was infused (0.2-1.0 mg/ml, 0.01-0.05 ml/min, 2-5 min) via the lingual
      artery catheter. During WBH, EBF increased from 0.39 +/- 0.08 to 6.47 +/- 0.63
      kHz in group 1, and from 0.69 +/- 0.18 to 5.72 +/- 0.49 kHz in group 2. Infusion
      of L-NAME decreased EBF in group 1 to 1.97 +/- 0.40 kHz. Infusion of saponin
      decreased EBF in group 2 to 1.23 +/- 0.40 kHz. Subsequent SNP infusion during
      hyperthermia returned EBF to 6.88 +/- 0.72 kHz in group 1 and 5.53 +/- 1.27 kHz
      in group 2 but had no effect when administered during normothermia. These results
      suggest that NO acts in conjunction with another substance, presumably the
      neurotransmitter released on WBH, to elicit thermoregulatory vasodilation.

PMID- 7503257
TI  - Adenosine A1 receptor-induced upregulation of protein kinase C: role of pertussis
      toxin-sensitive G protein(s).
AB  - Biochemical and pharmacological studies have established that adenosine modulates
      protein kinase C (PKC), which plays an important role in the maintenance of
      vascular tone. Our earlier studies [Marala and Mustafa. Am. J. Physiol. 268
      (Heart Circ. Physiol. 37): H271-H277, 1995. Marala, R. B., K. Ways, and S. J.
      Mustafa. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H1465-H1471, 1993] have
      shown the involvement of adenosine A1 receptors and not the A2 receptors in the
      upregulation of PKC in porcine coronary artery. The mechanism(s) by which
      adenosine upregulates PKC is not yet clearly understood. We now report the
      increased expression of PKC by adenosine A1 receptor through an upstream
      activation of pertussis toxin-sensitive G protein(s). Incubation of porcine
      coronary artery for 24 h with a relatively specific A1-receptor agonist (2S)-N6
      (2-endo-norbornyl)adenosine (ENBA) elevated the contractile responses to
      endothelin-1 by about twofold, probably due to an increased expression of PKC.
      Incubation of porcine coronary artery with ENBA also protected against the
      phorbol 12,13-dibutyrate (PDBu)-induced depletion of PKC. Inclusion of pertussis
      toxin in the incubation medium completely blocked both the upregulatory and the
      protective effects of ENBA. Incubation with pertussis toxin did not alter the PKC
      activity as judged by the contractile responses to PDBu. On the contrary,
      incubation of porcine coronary artery with cholera toxin for 24 h did not alter
      any of the ENBA responses (upregulation of PKC and the protection against PDBu
      induced PKC depletion). Incubation conditions of coronary arteries with toxins
      are sufficient to cause ADP ribosylation of respective G proteins as judged by
      back ADP ribosylation studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503258
TI  - Effects of thiol-modifying agents on KATP channels in guinea pig ventricular
      cells.
AB  - ATP-sensitive K+ (KATP) channels are thought only to open during conditions of
      metabolic impairment (e.g., myocardial ischemia). However, the regulation of KATP
      channel opening during ischemia remains poorly understood. We tested whether
      thiol (SH) group oxidation, which is known to occur during ischemia, may be
      involved in KATP channel regulation. Inside-out membrane patches were voltage
      clamped at a constant potential (O mV) in asymmetrical K+ solutions. The effects
      of compounds that specifically modify SH groups [p-chloromercuri-phenylsulfonic
      acid (pCMPS), 5-5'-dithio-bis(2-nitrobenzoic acid) [DTNB], and thimerosal] were
      tested. The membrane-impermeable compound, pCMPS (> or = 5 microM), caused a
      quick and irreversible inhibition of KATP channel activity. The reducing agent,
      dl-dithiothreitol (DTT) (3 mM) was able to reverse this inhibition. DTNB (500
      microM) caused a rapid, but spontaneously reversible, block of KATP channel
      activity. After DTNB, no change was observed in single channel conductance.
      Oxidized glutathione (GSSG, 3 mM) did not block KATP channel activity. Thimerosal
      (100-500 microM) induced a DTT-reversible block of partially rundown KATP
      channels, or channels that underwent complete rundown; these channels were
      reactivated with trypsin (1 mg/ml). Thimerosal did not block KATP channels that
      had a high degree of activity. However, the ATP sensitivity was decreased; the
      concentration of ATP needed to half-maximally inhibit the channel (Ki) was
      increased from 47 +/- 12 to 221 +/- 35 microM (n = 6, P < 0.05). This was not due
      to a spontaneous change with time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503259
TI  - ATP-sensitive K+ currents in cerebral arterial smooth muscle: pharmacological and
      hormonal modulation.
AB  - Calcitonin gene-related peptide (CGRP), hypoxia, and synthetic activators of ATP
      sensitive potassium (KATP) channels (e.g., pinacidil and levcromakalim) cause
      dilation of cerebral arteries that are attenuated by the KATP channel inhibitor
      glibenclamide. We have identified and characterized KATP currents in smooth
      muscle cells isolated from rabbit cerebral arteries, using the whole cell
      configuration of the patch-clamp technique. Pinacidil (10 microM) and
      levcromakalim (10 microM) increased glibenclamide-sensitive currents about
      sixfold in cells dialyzed with 0.1 mM ATP. Glibenclamide-sensitive currents in
      the presence of pinacidil were potassium selective, voltage independent, and
      reduced about threefold by elevating intracellular ATP from 0.1 to 3.0 mM.
      External tetraethylammonium and 4-aminopyridine at millimolar concentrations
      reduced pinacidil-induced currents, whereas iberiotoxin, a blocker of calcium
      activated potassium channels, had no effect. The vasoconstrictors serotonin and
      histamine also inhibited pinacidil-induced currents. The vasodilators CGRP and
      adenosine, in contrast, increased glibenclamide-sensitive potassium currents. We
      conclude that cerebral artery smooth muscle cells have KATP channels that are
      regulated by endogenous vasoconstrictors and vasodilators. We propose that these
      channels are involved in the dilation of cerebral arteries to CGRP and synthetic
      vasodilators.

PMID- 7503260
TI  - Multiple growth factors are released from mechanically injured vascular smooth
      muscle cells.
AB  - Local release of mitogenic and chemotactic signals during angioplasty-induced
      vascular injury may initiate restenosis. We investigated whether mechanical
      injury to vascular smooth muscle cells (VSMC) results in the release of
      biologically active peptide growth factors. Monolayers of bovine SMC cultures
      were mechanically injured by cell scraping. Conditioned medium (CM) from control
      and injured SMC cultures was collected, and the mitogenic activity was measured
      by [3H]thymidine incorporation in recipient SMC cultures. Mitogenic activity from
      injured CM was detected within 15 min after injury. When the CM from injured
      cells was removed 15 min after injury and replaced with serum-free media, there
      was no detectable mitogenic activity in the replacement CM assessed 1-6 days
      postinjury. Suramin, a nonspecific peptide growth factor antagonist,
      significantly inhibited the mitogenic activity of injured CM. Basic fibroblast
      growth factor (bFGF), platelet-derived growth factor (PDGF A chain), and
      epidermal growth factor (EGF) were detected in CM from injured cells by
      immunoblot analysis. The mitogenic activity of injured CM was significantly
      inhibited with neutralizing antibodies to bFGF (34%), PDGF-AA (32%), PDGF-BB
      (25%), and EGF (25%). A neutralizing antibody to transforming growth factor (TGF)
      beta had no effect. In conclusion, bFGF, PDGF, and EGF are immediately released
      from mechanically injured VSMC. VSMC likely contain preformed, biologically
      active growth factors that are efficiently released from the cell cytoplasm
      following mechanical injury. Conditioned medium from injured VSMC is highly
      mitogenic, and this activity is probably due to multiple growth factors
      interacting synergistically.

PMID- 7503261
TI  - The stable VIP analogue, Ro 24-9981, potentiates bradykinin-induced increases in
      clearance of macromolecules.
AB  - The purpose of this study was to determine whether the stable cyclic peptide
      analogue of human vasoactive intestinal peptide, Ro 24-9981, modulates bradykinin
      induced plasma exudation in the oral mucosa and if so, to determine the
      mechanisms that mediated these responses. Using intravital microscopy, we found
      that suffusion of Ro 24-9981 had no significant effects on leaky site formation
      and clearance of fluorescein-isothiocyanate-dextran (mol mass 70 kDa) in the
      hamster cheek pouch. However, Ro 24-9981 significantly potentiated bradykinin
      induced increases in leaky site formation and clearance of fluorescein
      isothiocyanate-dextran (P < 0.05). These effects were specific because Ro 24-9981
      had no significant effects on adenosine and calcium ionophore A23187-induced
      increases in leaky site formation and clearance of fluorescein-isothiocyanate
      dextran. Furthermore, they were not mediated by cyclooxygenase products of
      arachidonic acid metabolism because indomethacin was ineffective. NG-nitro-L
      arginine methyl ester, a selective inhibitor of nitric oxide synthase, but not NG
      nitro-D-arginine methyl ester, significantly attenuated the effects of both
      bradykinin and Ro 24-9981 with bradykinin (P < 0.05). These responses were
      restored by L-arginine but not D-arginine. Collectively, these data indicate that
      bradykinin-induced plasma exudation in the oral mucosa was potentiated by Ro 24
      9981 in a specific receptor-mediated fashion. These responses were mediated, in
      part, by the L-arginine/nitric oxide biosynthetic pathway.

PMID- 7503262
TI  - Effects of diabetes on isometric tension as a function of [Ca2+] and pH in rat
      skinned cardiac myocytes.
AB  - In diabetes a primary myocardial defect occurs that is characterized by decreases
      in systolic pressure and cardiac output. The present study investigates whether
      diabetes causes a decreased maximum tension-generating ability, decreased Ca2+
      sensitivity of myofilaments, or no change in cardiac myofilament contractile
      properties at pH 7.0 and 6.6. Hearts from Wistar rats were excised and
      mechanically disrupted 6-10 wk after injection of streptozotocin. The resulting
      myocyte-size preparations of skinned myocardium were used to determine the steady
      state tension-negative, log molar Ca2+ concentration (pCa) relation. Maximum
      tension was unchanged, and the pCa of half-maximum tension generation was 0.14
      pCa units lower than control for skinned myocytes from diabetic rats at pH 7.0. A
      significantly lower than normal maximum tension was observed at pH 6.6 for
      cardiac myocytes from diabetic rats. Increased expression of beta-myosin heavy
      chain (MHC) occurred in hearts from diabetic rats. Two troponin T (TnT) isoforms
      in myocardium of adult rats were identified by Western blots. The ratio of the
      two TnT isoforms were altered in diabetes. Changes in cardiac MHC and TnT
      expression may contribute to the observed decrease in Ca2+ sensitivity of
      myofilaments at pH 7.0 and decreased maximum tension-generating ability at pH 6.6
      in diabetes.

PMID- 7503263
TI  - Adrenergic responsiveness is reduced, while baseline cardiac function is
      preserved in old adult conscious monkeys.
AB  - To examine the physiological deficit to adrenergic stimulation with aging, five
      younger adult (3 +/- 1 yr old) and nine older adult (17 +/- 1 yr old) healthy
      monkeys were studied after instrumentation with a left ventricular (LV) pressure
      gauge, aortic and left atrial catheters, and aortic flow probes to measure
      cardiac output directly. There were no significant changes in baseline
      hemodynamics in conscious older monkeys. For example, an index of contractility,
      the first derivative of LV pressure (LV dP/dt) was similar (3,191 +/- 240, young
      vs. 3,225 +/- 71 mmHg/s, old) as well as in isovolumic relaxation, tau (24.3 +/-
      1.7 ms, young vs. 23.0 +/- 1.0 ms, old) was similar. However, inotropic,
      lusitropic, and chronotropic responses to isoproterenol (Iso; 0.1 micrograms/kg),
      norepinephrine (NE; 0.4 micrograms/kg), and forskolin (For; 75 nmol/kg) were
      significantly (P < 0.05) depressed in older monkeys. For example. Iso increased
      LV dP/dt by by 146 +/- 14% in younger monkeys and by only 70 +/- 5% in older
      monkeys. Iso also reduced tau more in younger monkeys (-28 +/- 7%) compared with
      older monkeys (-13 +/- 3%). Furthermore, peripheral vascular responsiveness to
      Iso, NE, For, and phenylephrine (PE; 5 micrograms/kg) was significantly (P <
      0.05) reduced in older monkeys. For example, phenylephrine (5 micrograms/kg)
      increased total peripheral resistence by 69 +/- 4% in younger monkeys and by only
      45 +/- 3% in older monkeys. Thus in older monkeys without associated
      cardiovascular disease, baseline hemodynamics are preserved, but adrenergic
      receptor responsiveness is reduced systemically, not just in the heart.

PMID- 7503264
TI  - Role of nitric oxide in adenosine receptor-mediated relaxation of porcine
      coronary artery.
AB  - In the present study, using porcine coronary artery rings in vitro, we examined
      the role of the nitric oxide (NO) pathway in endothelium-dependent vasorelaxant
      effects of the 5'-uronamide adenosine agonists, 5'-(N-ethylcarboxamido)adenosine
      (NECA) and 2-[p-(2-carboxyethyl)]phenylethyl-amino-5'-N-ethylcarboxamidoadenosine
      (CGS-21680) as opposed to the endothelium-independent actions of the C2- and N6
      substituted analogues, 2-chloroadenosine (CAD) and N6-cyclopentyladenosine (CPA).
      The NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 30 microM), and the
      NO-destroying agent, 6-anilino-5,8-quinolinedione (LY-83583, 10 microM),
      attenuated the relaxations of endothelium-intact but not -denuded rings to NECA
      and CGS-21680. The effect of L-NMMA on NECA-induced relaxation was reversed by L
      arginine (100 microM), a substrate for NO synthesis. In the endothelium-intact
      tissues, both NECA and CGS-21680 elicited enhanced production of nitrite, a
      stable metabolite of NO. This was also attenuated by L-NMMA or endothelium
      removal. Furthermore, NECA (10 microM) induced augmentation of guanosine 3',5'
      cyclic monophosphate (cGMP) production in the intact arteries, which was also
      inhibited by L-NMMA, LY-83583, or endothelium removal. In contrast, vasorelaxant
      responses generated by CAD and CPA were not altered by either L-NMMA or LY-83583.
      Both agents (10 microM) were also unable to alter nitrite and/or guanosine 3',5'
      cyclic monophosphate (cGMP) levels of the coronary artery.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7503265
TI  - Endothelium-dependent and -independent vasodilation of isolated rat aorta induced
      by caffeine.
AB  - Caffeine (10(-4)-10(-3) M) induced concentration-dependent relaxations of
      phenylephrine-precontracted rat aortic rings with endothelium. Endothelial
      denudation significantly, but only partially, attenuated caffeine-induced
      relaxation. Pretreatment with NG-nitro-L-arginine, oxyhemoglobin, and methylene
      blue attenuated the relaxations to an extent similar to endothelial denudation.
      Guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic
      monophosphate (cAMP) contents of aortic strips with endothelium increased
      significantly after exposure to caffeine (10(-3) M). Endothelial denudation
      attenuated caffeine-induced cGMP increase. Pretreatment with ryanodine (2 x 10(
      5) M), which has been shown to combine with receptors on endoplasmic reticulum
      (ER) of endothelium, attenuated caffeine-induced relaxation and cGMP content
      increase of rings with endothelium. Pretreatment with caffeine potentiated sodium
      nitroprusside-induced relaxations and cGMP increase of rings without endothelium.
      These results demonstrated that caffeine-induced relaxation comprises two
      components. In the endothelium-dependent mechanism, caffeine promotes nitric
      oxide synthesis in endothelium by release of Ca2+ from ER through a ryanodine
      sensitive Ca2+ channel, and the suppression of cGMP degradation also contributes
      to the relaxation. In the endothelium-independent mechanism, caffeine acts as a
      3',5'-cyclic-nucleotide phosphodiesterase inhibitor.

PMID- 7503266
TI  - Papillary muscles split in the presence of 2,3-butanedione monoxime have normal
      energetic and mechanical properties.
AB  - A number of studies have used 2,3-butanedione monoxime (BDM) to avoid myocardial
      damage when small muscle preparations were cut from large hearts. The present
      study investigates the mechanical and energetic effects of varying muscle cross
      sectional area (CSA) by dissection in physiological saline containing BDM. By use
      of adult rat hearts, three muscle groups were obtained: whole left ventricular
      papillary muscles (Whole) and left ventricular papillary muscles split
      longitudinally in the presence of 30 mM BDM, with removal of approximately 10%
      (BDMSP1) or 40-50% (BDMSP2) of the muscle (5 animals in each group). The isolated
      muscle preparations were studied at 27 degrees C and stimulated at 0.167 Hz. The
      Whole and BDMSP1 preparations had comparable CSAs; in isotonically contracting
      muscles working against a range of afterloads, work, enthalpy (energy use), and
      mechanical efficiency (work/enthalpy x 100%) were similar for the two groups. In
      addition, isometric performance [e.g., developed stress (force/CSA), length
      tension relationship, and contraction time course] was also similar for the two
      groups. The thinner BDMSP2 preparations showed an enhanced mechanical performance
      compared with the Whole and BDMSP1 groups. This outcome was in accordance with
      data in the literature documenting a negative correlation between stress and CSA.
      The results suggest that BDM-split and intact papillary muscles of similar CSA
      have comparable energetic and mechanical properties.

PMID- 7503267
TI  - Evaluation of T- and L-type Ca2+ currents in shark ventricular myocytes.
AB  - Two types of Ca2+ currents with characteristics of T- and L-type Ca2+ currents
      were recorded in ventricular myocytes of dogfish (Squalus acanthias). The T-type
      Ca2+ current activated near -70 mV and had a peak current density of 9.8 pA/pF at
      -34 mV. The L-type Ca2+ current activated near -50 mV and had a peak current
      density of 10.6 pA/pF near 0 mV. The threshold for activation of the T-type Ca2+
      current was 20 mV negative to that of the tetrodotoxin-sensitive Na+ current.
      Inactivation of the T-type Ca2+ current was rapid with a limiting time constant
      of 5 ms at positive potentials. The T-type Ca2+ current was not modulated by
      isoproterenol or acetylcholine. In dogfish the T-type Ca2+ channel has current
      densities equivalent to the L-type channel and is likely to activate before the
      Na+ channel, contributing significantly to generation of the foot of the action
      potential.

PMID- 7503268
TI  - Role of K+ATP channels and EDRF in reactive hyperemia in the hindquarters
      vascular bed of cats.
AB  - The mechanism underlying reactive hyperemia was investigated in the feline
      hindquarters vascular bed under natural- and constant-flow conditions. A 30-s
      occlusion of the distal aorta produced a marked hyperemic increase in distal
      aortic blood flow that was attenuated by the ATP-sensitive K+ (K+ATP) channel
      blocking agent, glibenclamide. When blood flow to the hindquarters vascular bed
      was held constant with a pump, interruption of blood flow for 5- to 90-s periods
      produced reactive vasodilator responses that increased in magnitude and duration
      as the period of ischemia increased. The magnitude and duration of the reactive
      vasodilator responses were reduced by K+ATP channel antagonists and an inhibitor
      of nitric oxide synthase, whereas indomethacin had no significant effect. In the
      pulmonary vascular bed, under constant-flow, elevated tone conditions, a 30-s
      period of ischemia produced a small reactive vasodilator response and a larger
      secondary vasoconstrictor response. The present data suggest that reactive
      hyperemia in the hindquarters vascular bed is mediated by the opening of K+ATP
      channels and nitric oxide release and that the reactive hyperemic response is not
      pronounced in the pulmonary circulation.

PMID- 7503269
TI  - Structure and hemodynamics of microvascular networks: heterogeneity and
      correlations.
AB  - The objective of this study was to quantify the heterogeneity of topological,
      morphological, and hemodynamic parameters in microvascular networks and to
      identify functionally relevant correlations among these parameters. Seven
      networks in the rat mesentery (383-913 vessel segments per network) were
      examined, and measurements were made of segment generation, diameter, length, and
      hematocrit in all segments (n = 3,129) and of flow velocity (only in 3 networks,
      1,321 segments). In addition, hematocrit, flow rate, and pressure were derived
      for all segments from a mathematical simulation. All parameters obtained exhibit
      heterogeneous distributions with coefficients of variation ranging from 0.28
      (capillary diameter) to > 1.5 (volume flow and pressure gradient). Several strong
      correlations exist between parameters, e.g., discharge hematocrit increases with
      vessel diameter, and shear rate increases with intravascular pressure. Because of
      such correlations, the extrapolation from average values for "typical vessels" to
      network properties can lead to substantial errors. For example, the mean network
      transit time estimated based on averaged quantities is 6.5 s, which is about 60%
      higher than the true value (4.08 s). Simplified models of the vascular bed may
      therefore be inadequate to describe functional properties of the
      microcirculation.

PMID- 7503270
TI  - Conducted vasodilation elevates flow in arteriole networks of hamster striated
      muscle.
AB  - Our purpose was to investigate blood flow responses to local and conducted
      vasodilation in arteriole networks supplying the cremaster muscle of anesthetized
      (pentobarbital sodium) male hamsters. We tested the hypothesis that with local
      release of a vasodilator onto an arteriole segment, conduction is necessary to
      increase arteriolar perfusion. The tips (OD, 1-2 microns) of micropipettes
      containing acetylcholine (ACh; 1.0 M) or sodium nitroprusside (NP; 0.2 M) were
      positioned approximately 1 mm distal to the origin of a 3A arteriole (resting
      diameter, 16 +/- 2 microns) originating at a "Y" bifurcation. Responses were
      monitored (n = 9) at the site of release (local) and at three upstream locations:
      at the vessel origin, in the parent (2A) arteriole (diameter, 24 +/- 3 microns),
      and in the paired (3A) daughter branch (diameter, 17 +/- 3 microns). At each
      upstream site, diameter and red blood cell velocity (Vrbc) were quantified at
      rest and during the peak of diameter responses; these variables were used to
      calculate blood flow and wall shear rate (WSR). Microiontophoresis (1 mA, 500 ms)
      of ACh increased local diameter by 13 +/- 4 microns (P < 0.05); vasodilation was
      conducted to each of the upstream sites (typical magnitude, 4-6 microns; P <
      0.05). Blood flow into branches increased 25-80% above corresponding values at
      rest without changing Vrbc; thus WSR consistently decreased with dilation (P <
      0.05). Microiontophoresis of NP induced similar dilation locally yet had no
      effect on diameter, blood flow, or WSR in network branches. Thus dilation of a
      distal arteriole segment alone had no effect on muscle blood flow.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7503271
TI  - Autonomic and ventilatory components of heart rate and blood pressure variability
      in freely behaving rats.
AB  - The relative role of parasympathetic, sympathetic, and ventilatory influences in
      the genesis of blood pressure and R-R interval variability is controversial. In
      13 freely behaving WKY rats instrumented with venous and arterial catheters and
      chest electrodes, mean arterial pressure (MAP, mmHg), R-R interval (ms), and
      respiratory fluctuations were monitored for 90 min in the control condition and
      after intravenous atropine (0.75 mg/kg) and/or propranolol (1 mg/kg). Spectral
      power (pw) in the 0.25- to 0.75-Hz (midfrequency, MF) and the 0.75- to 3.0-Hz
      (high-frequency, HF, respiratory-synchronous) bands was computed in sequences of
      400 heartbeats by use of a combined autoregressive analysis. Atropine reduced but
      did not abolish HF R-R interval pw (from 1.73 +/- 0.50 to 0.39 +/- 0.27 ms2, P <
      0.01) and halved HF MAP pw (from 0.41 +/- 0.30 to 0.21 +/- 0.12 mmHg2, P < 0.05),
      whereas propranolol did not affect HF pw of the R-R interval or MAP. Propranolol
      also failed to significantly modify MF R-R interval pw (from 0.48 +/- 0.44 to
      0.40 +/- 0.34 ms2, P = NS) or MF MAP pw (from 0.54 +/- 0.39 to 0.42 +/- 0.20
      mmHg2, P = NS), whereas atropine virtually abolished MF R-R interval pw (from
      0.48 +/- 0.44 to 0.01 +/- 0.01 ms2, P < 0.01) and also significantly reduced MF
      MAP pw (from 0.54 +/- 0.39 to 0.33 +/- 0.24 mmHg2, P < 0.01). The effects of
      combined blockade were similar to those of atropine alone.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7503274
TI  - Effect of acadesine treatment on postischemic damage to small intestine.
AB  - Hemorrhagic mucosal lesions are produced during intestinal ischemia and after
      reperfusion due at least in part to the accumulation and activation of
      polymorphonuclear leukocytes in the tissue. It has been shown in vitro that
      adenosine is instrumental in attenuating this pathophysiological process.
      Acadesine [5-amino-4-imidazolecarboxamide (AICA) riboside], a purine nucleoside
      analogue, increases the availability of adenosine in the tissue. The aim of the
      study was therefore to assess the influence of acadesine treatment on neutrophil
      accumulation, purine metabolism, and mucosal damage after intestinal ischemia and
      reperfusion. Intestinal ischemia was induced in cats by partial occlusion of the
      superior mesenteric artery for 2 h. Samples of the small intestine were exercised
      before and at the end of the hypotensive period as well as 10 and 60 min after
      reperfusion. Conjugated dienes, myeloperoxidase, and reduced and oxidized
      glutathione, as well as the purine metabolites, were determined in the tissue
      samples. The tissue was also examined histologically. Six cats received saline,
      and six cats were treated initially before ischemia with acadesine (2.5 mg/kg
      body wt i.v.) over 5 min as a bolus. Thereafter, acadesine (0.5 mg.kg-1.min-
      i.v.) was given continuously during ischemia and 30 min after reperfusion.
      Acadesine treatment significantly attenuated the mucosal lesions seen during
      reperfusion. This improvement was due at least in part to the inhibition of
      neutrophil accumulation, as judged by low myeloperoxidase levels. The prevention
      of neutrophil activation resulted most likely from increased adenosine
      concentrations in the intestinal tissue in the early reperfusion period.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7503272
TI  - Modulation of pacemaker activity of sinoatrial node cells by electrical load
      imposed by an atrial cell model.
AB  - To investigate the electrotonic modulation of sinoatrial (SA) node pacemaker
      activity by atrial muscle, single or multiple (2-7) SA node cells isolated from
      rabbit hearts were connected to a membrane model [resistance-capacitance (R-C)
      circuit] of an atrial cell through an external circuit that mimics the gap
      junctional conductance (Gc) between cells. When Gc was 0 nS (uncoupled
      conditions), all the preparations generated regular and stable spontaneous action
      potentials with a mean cycle length (SCL) of 263 +/- 45 ms (+/- SD, n = 35). Step
      increases of Gc were associated with a progressive prolongation of SCL. At
      sufficiently high values of Gc, the spontaneous activity became irregular and
      finally stopped. We defined the threshold Gc causing an appreciable SCL
      irregularity as the minimum Gc at which the ratio of SD to mean of SCL was > 0.3.
      The threshold Gc for a single SA node cell was calculated to be 0.58 nS. In the
      presence of acetylcholine (ACh; 0.05-0.2 microM), the coupling-induced inhibition
      of spontaneous activity was greatly increased, and the threshold Gc for a single
      SA node cell was decreased in a concentration-dependent manner. These findings
      show that the pacemaker activity of SA node cells is easily inhibited when the
      cells are coupled to a passive atrial cell model and the inhibition is amplified
      by ACh. Computer simulation using a modified Oxsoft HEART model indicates that
      the passive atrial cell model acts as a current sink, imposing a substantial
      outward current on the SA node cell, and ACh amplifies the effect by activating
      an additional outward current.

PMID- 7503273
TI  - Fructose-1,6-diphosphate or adenosine attenuate leukocyte adherence in
      postischemic skeletal muscle.
AB  - The purpose of this study was to determine whether fructose-1,6-diphosphate (FDP)
      or adenosine (Ado), administered at the onset of reperfusion, would prevent
      ischemia/reperfusion (I-R)-induced leukocyte adherence and microvascular
      dysfunction in skeletal muscle. Changes in vascular permeability and tissue
      neutrophil content were assessed by measurement of the solvent drag reflection
      coefficient (delta) for total plasma proteins and muscle myeloperoxidase (MPO)
      activity, respectively, in continuously perfused, isolated canine gracilis
      muscles and in muscles subjected to I-R alone, I-R + FDP, and I-R + Ado. To
      determine whether FDP or Ado would attenuate leukocyte-endothelial cell adhesive
      interactions induced by I-R, leukocyte adherence and emigration were assessed in
      postischemic mouse cremaster muscles, using intravital microscopy in the presence
      and absence of FDP or Ado during reperfusion. I-R was associated with a marked
      increase in microvascular permeability and muscle MPO activity relative to
      nonischemic controls. These increases were attenuated by FDP and Ado. I-R also
      increased the number of adherent and emigrated leukocytes relative to control. I
      R-induced leukocyte adherence and emigration were significantly attenuated by
      either FDP or Ado. These results indicate that FDP and Ado attenuate postischemic
      microvascular barrier dysfunction in skeletal muscle by a mechanism that may be
      related to their ability to inhibit leukocyte adhesion and emigration.

PMID- 7503275
TI  - Complexity and "chaos" in blood pressure after baroreceptor denervation of
      conscious dogs.
AB  - To investigate how arterial baroreceptors affect the dynamic properties of short
      term blood pressure control, we determined Lyapunov exponents and correlation
      dimensions of blood pressure. Two groups of conscious dogs were studied: a
      control group (n = 7) and a group subjected to total sinoaortic and
      cardiopulmonary baroreceptor denervation (n = 7). As a measure of variability,
      standard deviation was determined and power spectra were calculated. In the lower
      frequency range (f < 0.1 Hz) power density was inversely related to frequency in
      both groups, indicating "1/f noise." Estimating the correlation dimension via the
      Grassberger-Procaccia algorithm as a quantification of complexity revealed a
      decrease after baroreceptor denervation (1.74 +/- 0.2 vs. 3.05 +/- 0.23 control;
      P < 0.05). Determination of the largest Lyapunov exponents lambda 1, which
      indicates the sensitive dependence on initial conditions, a hallmark of chaos,
      also yielded a diminution after denervation (lambda 1 = 0.74 +/- 0.08 vs. 1.85 +/
      0.18, P < 0.01). The results were cross-checked with surrogate data statistics.
      The null hypothesis, that there is no nonlinear structure in arterial blood
      pressure time series, was rejected. This shows that after baroreceptor
      denervation, blood pressure control is less complex and less sensitive to initial
      conditions ("chaos"). In contrast, variability (standard deviation) is increased
      (22.2 +/- 3.1 denervation vs. 8.3 +/- 1.4 control; P < 0.05). It is concluded
      that under physiological conditions, arterial and cardiopulmonary baroreceptors
      reduce variability of blood pressure, however, at the cost of blood pressure
      being less predictable. Thus the regulation is more sensitive depending on
      initial conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503276
TI  - Ischemic preconditioning inhibits glycolysis and proton production in isolated
      working rat hearts.
AB  - The effect of ischemic preconditioning (IPC) on glycolysis, glucose oxidation,
      adenine nucleotide and nucleoside levels, and mechanical function was studied in
      isolated paced working rat hearts under aerobic conditions or when reperfused
      following sustained ischemia. IPC inhibited glycolysis in aerobic hearts (4.48 +/
      0.66 vs. 3.18 +/- 0.39 mumol.min-1.g dry wt-1) and calculated proton production
      attributable to exogenous glucose (7.79 +/- 1.31 vs. 4.73 +/- 0.81 mumol.min-1.g
      dry wt-1). In hearts subjected to ischemia and reperfusion, IPC decreased,
      relative to controls, glycogen content before the onset of ischemia (116.6 +/-
      4.3 vs. 158.0 +/- 8.4 mumol/dry wt) and decreased consumption of glycogen during
      ischemia (54 +/- 6 vs. 76 +/- 7 mumol/dry wt). During reperfusion, glycolysis was
      lower in IPC hearts (2.45 +/- 0.16 vs. 4.4 +/- 0.46 mumol.min-1.g dry wt-1), as
      was calculated proton production (3.57 +/- 0.30 vs. 8.38 +/- 0.93 mumol.min-1.g
      dry wt-1). Glucose oxidation was similar in control and IPC hearts. Adenosine and
      ATP content of IPC hearts, relative to controls, were higher at the end of
      ischemia, being 0.86 +/- 0.08 vs. 0.34 +/- 0.15 mumol/g dry wt and 11.3 +/- 0.8
      vs. 5.0 +/- 1.6 mumol/g dry wt, respectively. IPC enhanced recovery of
      ventricular work during reperfusion of ischemic hearts from 37 to 68%. These
      results indicate that IPC is associated with a reduction in glycogen content,
      inhibition of glycolysis during ischemia and reperfusion, and a decrease in
      proton production from glucose. These changes may, in part, explain the enhanced
      recovery of mechanical function observed in IPC hearts.

PMID- 7503277
TI  - Influence of brain injury on opioid-induced pial artery vasodilation.
AB  - This study was designed to investigate the effect of fluid percussion brain
      injury on opioid-induced pial artery vasodilation in the newborn pig. Previous
      observations have shown that brain injury produces pial artery vasoconstriction
      associated with elevated cerebral spinal fluid (CSF) opioid levels in the piglet.
      Additionally, opioids produce pial vasodilation that is attenuated by the nitric
      oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA). Anesthetized newborn
      pigs equipped with a closed cranial window were connected to a percussion device
      consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain
      injury of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum
      to strike a piston on the cylinder. Methionine enkephalin (Met), an endogenous mu
      opioid agonist in physiological and pharmacological concentrations (10(-10), 10(
      8), 10(-6) M), produced vasodilation that was attenuated following brain injury
      (7 +/- 1 vs. 3 +/- 1%, 11 +/- 1 vs. 5 +/- 1% and 16 +/- 1 vs. 8 +/- 1% for 10(
      10), 10(-8), 10(-6) M Met before and after injury, respectively, n = 5). Met
      induced dilation was associated with increased cortical periarachnoid CSF
      guanosine 3',5'-cyclic monophosphate (cGMP), and these biochemical changes were
      blunted by brain injury (342 +/- 12 and 640 +/- 13 fmol/ml vs. 267 +/- 6 and 321
      +/- 17 fmol/ml for control and Met 10(-6) M before and after injury,
      respectively, n = 5). Leucine enkephalin, an endogenous delta-agonist, induced
      pial dilation and associated changes in CSF cGMP, which were similarly altered by
      brain injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503278
TI  - Nifedipine inhibits movement of cardiac calcium channels through late, but not
      early, gating transitions.
AB  - L-type Ca2+ channels were studied in guinea pig ventricular myocytes by examining
      how photoinactivation of nifedipine affected the Ca2+ current (ICa) and the Ca2+
      channel gating current (Ig). ICa, blocked by nifedipine, reappeared in
      qualitatively different phases (immediate and delayed) following
      photoinactivation of nifedipine. Immediate recovery was attributed to unblock of
      closed Ca2+ channels, while delayed recovery was attributed to unblock of
      inactivated channels. In contrast to the ICa results, photoinactivation of
      nifedipine produced only delayed recovery of Ig. Analysis of these results
      suggests the following conclusions. First, the actions of inhibitory
      dihydropyridines can be attributed to binding to either the inactivated or the
      closed conformation, but only binding to the inactivated state is associated with
      reduction of Ig. Second, the action of inhibitory dihydropyridines on closed
      channels is to retard their movement through a final, voltage-independent
      transition to the open state. This effect seems to be the converse of a major
      action of stimulatory dihydropyridines and thus is the principal mechanistic
      difference between stimulatory and inhibitory dihydropyridines.

PMID- 7503280
TI  - L-NNA suppresses cerebrovascular response and evoked potentials during
      somatosensory stimulation in rats.
AB  - We studied the local cerebrovascular response and somatosensory-evoked potentials
      (SEPs) to stimulation of the sciatic nerve during both short- (< 30 min) and long
      term (90-150 min) exposure to topically applied NG-nitro-L-arginine (L-NNA). The
      pial circulation was visualized through a cranial window in alpha-chloralose
      anesthetized rats. The diameter of pial arterioles (25-45 microns) and laser
      Doppler flow (LDF) in the hindlimb sensory cortex were simultaneously measured
      during sciatic nerve stimulation. Short-term (< 30 min) treatment with L-NNA (1
      mM) abolished the dilation of pial arterioles induced by acetylcholine, whereas
      the response to sciatic nerve stimulation was not affected. When applied for > 30
      min, L-NNA induced severe vasomotion and attenuated the vascular responses to
      sciatic nerve stimulation. Long-term exposure to topically (1 mM) or systemically
      (10 mg/kg i.v.) applied L-NNA also attenuated cortical SEPs to sciatic nerve
      stimulation. Thus L-NNA-induced inhibition of vascular responses may be secondary
      to suppression of neuronal activity and an L-arginine metabolite, such as nitric
      oxide, may be involved in neurotransmission in the cerebral cortex during
      somatosensory activity.

PMID- 7503279
TI  - Identification and activation of autocrine renin-angiotensin system in adult
      ventricular myocytes.
AB  - To date, the demonstration that the molecular components of the renin-angiotensin
      system (RAS) are present in adult ventricular myocytes is lacking. In addition,
      whether the RAS is upregulated under conditions of overload and myocyte
      hypertrophy in vivo remains to be determined. By employing an in vivo model of
      ischemic cardiomyopathy in rats, we document that adult myocytes express genes
      for renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin
      II (ANG II) receptors. Moreover, renin, ACE, and ANG II receptor mRNAs increased
      in stressed myocytes undergoing cellular hypertrophy. At the protein level, the
      percentage of myocytes containing renin, ANG I, and ANG II was significantly
      increased in the overloaded heart. The number of binding sites for ANG II per
      myocyte also markedly increased under this setting. These results provide direct
      evidence of the existence of a myocyte RAS, which may be activated in
      pathological states of the heart to support myocyte growth and contractile
      function.

PMID- 7503282
TI  - Microvascular blood volume-to-flow relationships in porcine heart wall: whole
      body CT evaluation in vivo.
AB  - The goal of this study was to evaluate the functional behavior of recruitable
      (mostly capillary) and nonrecruitable (mostly arterioles and venules) components
      of the intramyocardial microvasculature in the in situ heart of intact
      experimental animals. For this purpose fast X-ray computerized tomography (CT)
      scans were performed in a group of anesthetized pigs. Each scan was performed
      during an aortic root angiogram and was repeated after sequential injections of a
      suspension of nonradioactive microspheres into a selected coronary artery.
      Regional myocardial perfusion (F, ml.g-1.min-1) and intramyocardial blood volume
      (rho, ml/g) were estimated from the dynamic CT image sequences. For the
      intramyocardial microcirculation, rho = AF + B square root of F [where A = 0.016
      min and B = 0.076 (ml.min/g)1/2] was shown to describe the rho-to-F relationship
      over the entire range of flows observed. With increasing embolization with 15
      microns diameter microspheres, the coefficients A and B changed in a way
      consistent with A describing the transit time through the functionally
      recruitable component and B/ square root of F describing the transit time through
      the functionally nonrecruitable component of the microcirculation.

PMID- 7503281
TI  - Pulmonary vascular extraction and distribution of antipyrine with alveolar
      flooding.
AB  - Transport characteristics of antipyrine (AP), 22Na+, and tritiated water (THO)
      were assessed in dog lungs by multiple indicator-dilution experiments in vivo
      with anesthesia and in isolated perfused preparations before and after alveolar
      flooding. In controls, outflow patterns of AP and THO were nearly identical. In
      flooding, AP and THO patterns separated. THO upslopes decreased and mean (t) and
      modal (tmax) transit times increased as flooding increased; AP initial upslopes
      remained relatively unchanged but t increased, whereas tmax decreased. Patterns
      of 22Na+ were unchanged. The results indicate 22Na+ limitation at the
      endothelium, AP limitation only at the epithelium, and no THO limitation. A
      mathematical model is based on axial and orthogonal distribution of AP and THO.
      With alveolar flooding, diffusional distance may be a limiting factor in this
      distribution.

PMID- 7503283
TI  - VEGF gene expression is upregulated in electrically stimulated rat skeletal
      muscle.
AB  - Vascular endothelial growth factor (VEGF; also called vascular permeability
      factor) is a secreted mitogen with distinct target cell specificity for vascular
      endothelial cells. Hypoxia upregulates VEGF expression, making it a likely
      mediator of the angiogenesis that occurs in poorly perfused tissues. The purpose
      of this study was to determine whether VEGF gene expression is upregulated in
      chronically stimulated skeletal muscles, where hypoxia is thought to trigger the
      growth of blood vessels. The right anterior tibialis and extensor digitorum
      longus muscles of 12 rats were stimulated electrically (10 Hz, 300 microseconds
      pulses) for up to 21 days by way of the peroneal motor nerve. The contralateral
      muscles served as control. Northern analysis showed that VEGF mRNA levels
      increased by approximately sixfold after 4 days of stimulation and then decreased
      gradually over the next several days. VEGF mRNA levels were still elevated by two
      to threefold after 21 days of stimulation. Higher VEGF mRNA levels in the early
      stages of muscle stimulation and gradually decreasing levels in later stages are
      consistent with a metabolic hypothesis in which tissue oxygenation controls VEGF
      expression. These studies support the hypothesis that VEGF has a physiological
      role in promoting angiogenesis in stimulated skeletal muscle.

PMID- 7503284
TI  - Single-nephron adaptations to partial renal ablation in cats.
AB  - To evaluate remnant nephron hyperfiltration, cats underwent sham surgery (group
      1, n = 6) or three-fourths nephrectomy (group 2, n = 6). Four to six weeks later,
      micropuncture studies demonstrated increases (P < 0.01) of single-nephron
      glomerular filtration rate (SNGFR) in group 2 (28.1 +/- 2.8 vs. 56.0 +/- 5.9
      nl/min). In group 2 the mean estimated glomerular capillary pressure of 74.0 +/-
      1.7 mmHg exceeded (P < 0.01) the value for group 1 (62.6 +/- 1.4 mmHg). The mean
      effective filtration pressure (EFPm) for group 2 (28.7 +/- 3.1 mmHg) was greater
      (P < 0.05) than that in group 1 (20.8 +/- 1.9 mmHg). Similarly, the mean
      ultrafiltration coefficient (Kf) in group 2 of 2.03 +/- 0.24 nl.min-1.mmHg-1
      exceeded (P < 0.05) the corresponding value for group 1 of 1.35 +/- 0.06 nl.min
      1.mmHg-1. Morphological studies demonstrated glomerular enlargement and mesangial
      matrix expansion in group 2 (P < 0.05). Proteinuria, as assessed by the urine
      protein-to-creatinine ratio, was increased (P < 0.05) after partial renal
      ablation. These results demonstrate that increases in SNGFR in feline remnant
      nephrons occur in association with glomerular hypertension, glomerular
      hypertrophy, expansion of mesangial matrix, and proteinuria, and furthermore,
      that the observed increases in SNGFR are attributable to an augmentation of EFPm
      and Kf.

PMID- 7503285
TI  - Angiotensin II modulates arterial baroreflex function via a central alpha 1
      adrenoceptor mechanism in rabbits.
AB  - To test the hypothesis that angiotensin II (ANG II) modulates arterial baroreflex
      function via a central alpha 1-adrenoceptor mechanism, we examined the effects of
      intravertebral infusion of ANG II on baroreflex function curves before and after
      intravertebral administration of the alpha 1-adrenoreceptor antagonist prazosin.
      Rabbits were chronically instrumented with subclavian and vertebral arterial
      catheters, venous catheters, and aortic and vena caval occludes. Baroreflex
      curves were obtained by relating heart rate (HR) to mean arterial pressure during
      increases and decreases in arterial pressure. Intravertebral infusions of ANG II
      (5, 10, and 20 ng.kg-1.min-1) produced a dose-dependent shift of the midrange of
      the curve toward higher pressures (64 +/- 1 to 68 +/- 1, 76 +/- 1, and 85 +/- 2
      mmHg, respectively). Pretreatment with prazosin (10 micrograms/kg) via the
      vertebral artery markedly reduced the shift in the baroreflex curve induced by
      the highest dose of ANG II (64 +/- 2 to 70 +/- 2 mmHg). These data suggest that
      ANG II resets the operating point of the HR baroreflex curve to a higher blood
      pressure and that this effect is mediated via a central alpha 1 mechanism. When
      the effects of vertebral ANG II on the baroreflex control of renal sympathetic
      nerve activity (RSNA) were examined, intravertebral administration of ANG II,
      while reducing the gain and the maximum RSNA, did not reset the RSNA baroreflex
      curve. These data suggest that ANG II acutely resets the HR baroreflex but not
      the RSNA baroreflex and that the resetting involves an alpha 1-adrenergic
      mechanism.

PMID- 7503286
TI  - Pancreatic somatostatin-14 and somatostatin-25 release in rainbow trout is
      stimulated by glucose and arginine.
AB  - Previous work suggested that teleost fish possess two somatostatin (SS) genes.
      Regulation of differential secretion of SS gene I (SS-25) and SS gene II products
      (SS-14) by nutrients was studied using rainbow trout. Hemi-islets were cultured
      in medium containing different concentrations of glucose and arginine. SS-14 and
      insulin were determined by radioimmunoassay; SS-25 was determined by a novel
      enzyme-linked immunosorbent assay. Glucose stimulated SS-25 release in a
      concentration-related manner, with 10 mM being the most effective concentration;
      at higher (25 mM) glucose, release decreased. Insulin levels in the medium also
      were found to be more elevated from islets incubated in 10 mM glucose than those
      incubated in 25 mM glucose. Maximum SS-14 release was observed at lower (1-5 mM)
      glucose concentrations. Arginine stimulated SS release so that maximum release of
      both SS forms occurred at the lowest glucose concentrations (1 mM). A
      concentration-related effect of arginine was observed on SS-25 release. The
      results of this study indicate that glucose and arginine regulate secretion of
      both pancreatic SS gene I and gene II products from rainbow trout islets,
      suggesting that two different pancreatic SS interact in nutrient homeostasis in
      this species.

PMID- 7503287
TI  - Body energy status and the metabolic response to acute inflammation.
AB  - An animal model of acute inflammation was used to examine how body energy status
      influences the syndrome of anorexia, negative nitrogen balance, and body weight
      loss typically seen in response to injury. Specifically, the metabolic response
      to acute inflammation was studied in rats of normal, elevated, or reduced body
      weights. Rats induced to overeat and gain weight prior to inflammation displayed
      protracted anorexia, greater subsequent weight loss, higher metabolic rates, and
      greater negative energy balance than rats of normal weight. Conversely, rats with
      reduced body weights displayed elevated food intakes, body weight gain,
      attenuated nitrogen loss, and normal rates of energy expenditure. Prior weight
      reduction did not affect postinflammation fever or levels of fibrinogen, iron,
      and interleukin-6-like activity, suggesting that the ability to mount an acute
      phase response was not impaired in weight-reduced rats. These results suggest
      that the usual postinflammation adjustments in body energy flux and body nitrogen
      are regulated components of a metabolic response to acute inflammation which
      renders normally protected sources of endogenous energy and substrate available
      for repair and recovery.

PMID- 7503288
TI  - Interleukin-1 beta enhances spinal cord blood flow after intrathecal
      administration in the normal rat.
AB  - The effects of acute intrathecal recombinant human interleukin-1 beta (rhIL-1
      beta) administration on spinal cord blood flow (SCBF), volume, and velocity were
      determined by laser-Doppler flowmetry in normal anesthetized rats with the use of
      a randomized and blinded protocol. The intrathecal administration of rhIL-1 beta
      (0.16-16 ng) produced a dose-dependent increase in SCBF that was not related to
      changes in blood pressure; arterial pH, PO2, PCO2; or spinal cord temperature.
      The IL-1 beta-induced enhancement of SCBF was directly proportional to the
      resultant elevation of spinal cord rhIL-1 beta content and was significantly
      correlated with an elevated blood velocity. The IL-1 receptor antagonist (IL-1ra)
      in concentrations 50- and 200-fold higher than IL-1 beta completely blocked the
      IL-1 beta-induced increase in SCBF when both compounds were administered
      concomitantly, but when administered alone, IL-1ra did not affect SCBF or other
      parameters. This suggests that IL-1 beta action was mediated by a specific
      interaction with an IL-1 membrane receptor site. The results suggest a role of IL
      1 beta in the regulation of spinal cord hemodynamics. A potential pharmacological
      approach using IL-1 agonists for the treatment of the delayed appearance of
      posttraumatic spinal ischemia is proposed.

PMID- 7503289
TI  - Circadian rhythms of temperature and activity in obese and lean Zucker rats.
AB  - The circadian timing system is important in the regulation of feeding and
      metabolism, both of which are aberrant in the obese Zucker rat. This study tested
      the hypothesis that these abnormalities involve a deficit in circadian regulation
      by examining the circadian rhythms of body temperature and activity in lean and
      obese Zucker rats exposed to normal light-dark cycles, constant light, and
      constant dark. Significant deficits in both daily mean and circadian amplitude of
      temperature and activity were found in obese Zucker female rats relative to lean
      controls in all lighting conditions. However, the circadian period of obese
      Zucker rats did not exhibit differences relative to lean controls in either of
      the constant lighting conditions. These results indicate that although the
      circadian regulation of temperature and activity in obese Zucker female rats is
      in fact depressed, obese rats do exhibit normal entrainment and pacemaker
      functions in the circadian timing system. The results suggest a deficit in the
      process that generates the amplitude of the circadian rhythm.

PMID- 7503290
TI  - Lateral parabrachial serotonergic mechanisms: angiotensin-induced pressor and
      drinking responses.
AB  - This study investigated the effects of bilateral injections of serotonergic
      receptor ligands into the lateral parabrachial nucleus (LPBN) on the pressor and
      dipsogenic responses induced by intracerebroventricular (i.c.v.) injection of
      angiotensin II (ANG II). Rats with stainless steel cannulas implanted bilaterally
      into the LPBN and into the left lateral ventricle were used to study i.c.v. ANG
      II-induced water intake and pressor responses. Pretreatment with the serotonergic
      5-HT1/5-HT2 receptor antagonist methysergide (1-8 micrograms/200 nl) bilaterally
      injected into the LPBN increased the water intake induced by i.c.v. ANG II (50
      ng/microliters) administered via the lateral ventricle, but pretreatment with
      methysergide (4 micrograms/200 nl) did not change the pressor response produced
      by i.c.v. ANG II. After bilateral injection of either serotonin (5-HT, 5
      micrograms/200 nl) or the serotonergic 5-HT2a/5-HT2c receptor agonist (+/-)-2,5
      dimetoxy-4-iodoamphetamine hydrochloride (DOI; 0.5-10 micrograms/200 nl) into the
      LPBN, the water intake induced by ANG II was significantly reduced. These results
      are consistent with Other observations indicating that the LPBN is associated
      with inhibitory mechanisms controlling water intake induced by ANG II treatment
      and suggest that serotonergic pathways may be involved in this effect.

PMID- 7503291
TI  - Characterization of organic cation transport by avian renal brush-border membrane
      vesicles.
AB  - Organic cations are actively secreted by the renal proximal tubule. Studies on
      perfused tubules and isolated membranes from mammals and reptiles have
      demonstrated that organic cations (OC) are transported across the luminal (brush
      border) membrane by OC/H+ exchange. Our objective was to determine whether a
      similar mechanism was present in the avian kidney. Uptake of
      [14C]tetraethylammonium (TEA) was assayed under various ionic conditions by rapid
      filtration in brush-border membrane vesicles (BBMV) isolated from chicken kidney
      (Gallus domesticus). An outwardly directed proton gradient (pHin = 6.0: pHout =
      7.5) stimulated concentrative TEA uptake. TEA/H+ exchange was saturable, having a
      maximal rate of uptake of approximately 25 nmol.mg protein-1.min-1 and a
      Michaelis constant for TEA of approximately 500 microM. TEA transport could be
      indirectly coupled to sodium transport. Unlabeled TEA, N'-methylnicotinamide
      (NMN), choline, cimetidine, mepiperphenidol, quinidine, quinine, and ranitidine
      markedly cis-inhibited uptake of [14C]TEA. However, the organic anions probenecid
      and p-aminohippurate poorly inhibited uptake. Unlabeled TEA and NMN also trans
      stimulated [14C]TEA uptake. Thus, in avian renal BBMV, organic cations are
      transported by an OC/H+ exchange mechanism qualitatively similar to that present
      in mammals.

PMID- 7503292
TI  - Selectivity of fatty acid mobilization: a general metabolic feature of adipose
      tissue.
AB  - This study extends our earlier work (T. Raclot and R. Groscolas. J. Lipid Res.
      34: 1515-1526, 1993), which showed that, under norepinephrine-stimulated
      lipolysis, fatty acids of rat retroperitoneal fat cells are selectively
      mobilized. The present study examines whether this selective mobilization of
      fatty acids 1) is based on their proportions in adipose tissue, 2) is a metabolic
      feature common to all adipose tissues, and/or 3) depends on the lipolysis
      stimulating agent. Rat fat cells with two markedly different fatty acid
      compositions were isolated from four white adipose tissues and treated with three
      lipolytic agents. Fatty acid composition of in vitro released free fatty acids
      was compared with that of fat cell triacylglycerols, the ratio of percent in free
      fatty acid to percent in triacylglycerol being defined as the relative
      mobilization rate (RMR). The RMR of individual fatty acids was related to their
      molecular structure. It increased exponentially with unsaturation for a given
      chain length and decreased with increasing chain length for a given unsaturation.
      The selectivity of fatty acid mobilization was similar regardless of the fatty
      acid composition of adipose tissue, the tissue location, and the lipolytic agent
      used. Under conditions of stimulated lipolysis, the selectivity of fatty acid
      mobilization is therefore a general metabolic feature of adipose tissue. Fatty
      acids with 16-20 carbon atoms and 4 or 5 double bonds had the highest RMR (from
      1.4 to > 5), whereas fatty acids with 20-22 carbon atoms and 0 or 1 double bond
      had the lowest RMR (from 0.3 to 0.7). For the other fatty acids, RMR was close to
      unity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503293
TI  - Role of hemodilution on renal responses to water immersion in humans.
AB  - The present experiments were designed to elucidate 1) the role of the lower
      extremity capillary bed in decreasing plasma colloid osmotic pressure (COP)
      during immersion of humans (n = 8) for 6 h, and 2) the extent to which the
      natriuresis of water immersion is triggered by this decrease in COP. Irrespective
      of the depth, COPs were very similar during the immersion procedures, varying
      between 25.3 +/- 0.5 and 26.4 +/- 0.6 mmHg, which was significantly lower than
      during control (28.3 +/- 0.3 and 28.6 +/- 0.3 mmHg). During neck immersion,
      central venous pressure rose instantly by approximately 12 mmHg (P < 0.05) and
      remained elevated. Only a transient, marginal increase (1.6 +/- 0.7 mmHg)
      occurred during hip immersion. Cumulated sodium excretion during seated control,
      hip immersion, and neck immersion, respectively, differed significantly (30 +/-
      5, 45 +/- 5, and 101 +/- 6 mmol). It is concluded that the decrease in COP during
      immersion is primarily due to fluid shifts occurring in the capillary bed of the
      legs and that this may account for up to 25% of the immersion-induced increase in
      renal sodium excretion.

PMID- 7503294
TI  - Anoxic brain failure in an ectothermic vertebrate: release of amino acids and K+
      in rainbow trout thalamus.
AB  - The release of excitatory amino acids such as glutamate contributes greatly to
      anoxic and/or ischemic brain damage in mammals. However, for anoxia-intolerant
      ectothermic vertebrates, there has been no information on how anoxia affects
      extracellular amino acid levels, or how such changes relate temporally to major
      ion movements. We have investigated the effects of environmental anoxia on
      extracellular amino acid and K+ concentrations in rainbow trout thalamus in vivo
      at 15 degrees C, using microdialysis and K(+)-selective microelectrodes. Systemic
      blood pressure was also monitored. In separate experiments, endogenous
      neurotransmitter release was provoked by perfusing the microdialysis probe with a
      high-K+ Ringer solution, thereby establishing which amino acids are released by
      depolarization. Anoxia exposure resulted in the release of several amino acids,
      including glutamate, aspartate, gamma-aminobutyric acid (GABA), glycine, and
      taurine. GABA release appeared to be delayed compared with that of glutamate, for
      example. The loss of ion homeostasis (starting after 23 min) preceded the release
      of amino acids (starting after > or = 45 min). The amino acid release had no
      apparent effect on the rate of increase in extracellular K+. Thus, if these
      events are interrelated, the loss of ion homeostasis is likely to trigger the
      amino acid release but not vice versa.

PMID- 7503295
TI  - Drinking after intragastric NaCl without increase in systemic plasma osmolality
      in rats.
AB  - Drinking after intragastric hypertonic solutions was examined to determine
      whether increased plasma osmolality always accompanied initiation of drinking. A
      2-ml infusion through a gastric catheter was the beginning of tests in Sprague
      Dawley male rats. Latency to drink was shorter and 1-h water intake was greater
      for increasing concentrations of NaCl (600, 1,200, and 1,800 mosmol/kg) compared
      with baseline (290 mosmol/kg). Although 600, 900, or 1,200 mosmol/kg NaCl
      elicited drinking, such infusions failed to change systemic plasma osmolality,
      and 900 mosmol/kg also failed to change plasma sodium, protein, renin activity,
      or packed cell volume at the initiation of drinking. Intragastric 900 mosmol/kg
      sodium bicarbonate, sodium isethionate, potassium chloride, lithium chloride, and
      mannitol differentially increased water intake. Total subdiaphragmatic vagotomy
      abolished drinking elicited by intragastric NaCl; selective gastric or hepatic
      vagotomy attenuated intake under some conditions. These results support the
      hypothesis of a vagally mediated, gastrointestinal and/or hepatic-portal,
      osmosensitive mechanism for initiation of drinking in advance of postprandial
      increases in systemic osmolality.

PMID- 7503296
TI  - Endothelin acts as a paracrine regulator of stretch-induced atrial natriuretic
      peptide release.
AB  - Several lines of evidence suggest a paracrine regulatory role for endothelin (ET)
      in the release of atrial natriuretic peptide (ANP). To investigate this
      possibility, we used the ET A-type receptor (ETA-R) competitive inhibitor cyclo(D
      Asp-Pro-D-Val-Leu-D-Trp) (BQ-123) in isolated perfused atria to determine the
      effect of endogenously produced ET on the release of ANP. Initially, we found
      that high pressure (8-10 mmHg) increased the mean ANP secretion rate by 117.3 +/-
      21.2% (P < 0.05). Next, we found that at high pressure 50 nM of exogenously
      applied ET significantly augmented the stretch-induced release of ANP (P < 0.05)
      and that this response could be significantly attenuated in a dose-dependent
      manner by 1 and 3 microM BQ-123 (P < 0.05). These experiments proved the efficacy
      of the inhibitor in our model. Subsequently, we found that the stretch-induced
      release of ANP was significantly reduced to 51.5 +/- 13.0 and 22.3 +/- 11.8% by 1
      and 3 microM BQ-123, respectively (P < 0.05). Because the perfused atria model
      eliminates systemic cardiovascular effects, allows control and direct recording
      of the intra-atrial pressure, and preserves the potential endothelium-myocyte
      control system, we conclude that the stretch-induced release of ANP is partially
      regulated by ET and that the ET is locally produced and constitutes a paracrine
      control system.

PMID- 7503297
TI  - Hypothalamic NPY and prepro-NPY mRNA in Djungarian hamsters: effects of food
      deprivation and photoperiod.
AB  - Two catabolic states leading to loss of body weight were compared in the
      Djungarian hamster (Phodopus sungorus campbelli). Hypothalamic neuropeptide Y
      (NPY) and gene expression for NPY and corticotropin-releasing factor (CRF) were
      examined after withdrawal of food for 48 h or exposure to short photoperiod for
      10 or 20 wk. Food deprivation was accompanied by increases in both NPY and prepro
      NPY mRNA in the hypothalamic arcuate nucleus (ARC). Increases in gene expression
      were limited compared with published data from the rat and were inversely related
      to predeprivation body weight. Exposure to short photoperiod for 20 wk reduced
      body weight by 39%, but the activity of the NPY-ergic system was not affected;
      peptide concentration and gene expression were similar in short photoperiod
      hamsters and long photoperiod controls. The hypothalamic NPY-ergic system of the
      Djungarian hamster is sensitive to weight loss due to imposed manipulations of
      energy balance, but the catabolism observed in short photoperiod gives rise to a
      body weight that is appropriate to the season encoded by the photoperiod. CRF
      gene expression was not affected by food deprivation or short photoperiod.

PMID- 7503298
TI  - Effect of acute manipulation of blood volume and osmolality on plasma [AVT] in
      seawater flounder.
AB  - Chronically cannulated seawater (SW)-adapted flounder (Platichthys flesus) were
      used unanesthetized and unrestrained in an experimental series that acutely
      manipulated blood volume and plasma osmolality to determine their influence on
      plasma arginine vasotocin (AVT) concentrations. Immunoreactive AVT was measured
      using a radioimmunoassay validated for flounder and other teleosts. After
      hemorrhage-induced hypovolemia or hypervolemia produced by saline infusion, no
      major changes in plasma AVT concentrations were detected. Raising plasma
      osmolality by intraperitoneal injection of 1 M NaCl compared with control 150 mM
      NaCl-injected fish (329.4 +/- 3.4 vs. 320.4 +/- 3.0 mosmol/kgH2O, P < 0.05)
      produced an increase in plasma AVT concentration (6.7 +/- 1.2 vs. 4.2 +/- 0.2
      fmol/ml, P < 0.05). In a separate study, plasma composition in a large number of
      uncannulated SW-adapted flounder was determined. This demonstrated a positive
      linear relationship between the natural variation in plasma AVT concentrations
      and plasma osmolality and Na+ and Cl- concentrations observed between fish. These
      data indicate that AVT secretion in SW-adapted flounder is closely related and
      perhaps directly sensitive to changes in plasma tonicity.

PMID- 7503299
TI  - Cholesterol content of trout plasma membranes varies with acclimation
      temperature.
AB  - Involvement of cholesterol in thermally induced restructuring of biological
      membranes was investigated in several tissues of rainbow trout (Oncorhynchus
      mykiss). Cholesterol-rich plasma membranes (PM) were isolated from erythrocytes,
      liver, kidney, and gill of fish acclimated to 5 and 20 degrees C. Mean PM
      cholesterol-to-phospholipid molar ratios (C/P) from warm-acclimated animals were
      significantly higher than those of cold-acclimated fish in liver (0.26 vs. 0.18;
      P < 0.01), kidney (0.49 vs. 0.40; P < 0.02), and gill (0.66 vs. 0.60; P < 0.05);
      erythrocyte C/P did not differ significantly with acclimation temperature (0.28
      vs. 0.25; P = 0.25). In light of the ordering effects of cholesterol on fluid
      phase membranes, these results are consistent with a role for cholesterol in the
      homeoviscous response of some poikilotherm PMs. Tissue differences in both PM
      cholesterol levels and the magnitude of thermally evoked cholesterol changes may
      reflect tissue-specific membrane functions. Lower PM C/P of trout tissues
      relative to corresponding data available for homeotherms also support a possible
      evolutionary relationship between cholesterol content and thermal adaptation of
      the PM.

PMID- 7503300
TI  - Blood pressures and heart rate during larval development in the anuran amphibian
      Xenopus laevis.
AB  - Heart rate and blood pressure were measured in lightly anesthetized developing
      Xenopus laevis from hatching (body mass approximately 3 mg) to the end of
      metamorphosis (< or = 1 g). Blood pressures in the conus arteriosus, truncus
      arteriosus, and ventricle were measured by a servo-null micropressure system.
      Heart rate was determined from blood pressure recordings, and cardiac cycles were
      videotaped through a dissecting microscope. Heart rate varied from 50 to 150
      beats/min and showed a negative correlation with body mass, with a slope less
      than predicted from allometric equations based on adult vertebrates. Mean truncus
      pressures showed a positive correlation with body mass, increasing from 4 mmHg in
      a 25-mg larva to 9 mmHg in a 1-g larva. The pressure waveform during ventricular
      systole was similar in all developmental stages examined, whereas those in conus
      and truncus varied with development. Conus pressures differed distinctly from
      truncus pressure during diastole in all larvae examined, suggesting the existence
      of functional valves between conus and truncus as early as stage 46 of the
      Nieuwkoop-Faber larval staging system. Although the developmental patterns of
      heart rate and blood pressure in X. laevis showed significant correlation with
      body mass, body mass explained less than one-half of the variation in these
      variables. Therefore developmental factors other than body mass, such as changes
      in heart mass and the addition of new resistance vessels, may influence heart
      rate and blood pressure during development in X. laevis.

PMID- 7503301
TI  - Cardiac output and peripheral resistance during larval development in the anuran
      amphibian Xenopus laevis.
AB  - Stroke volume (SV) and cardiac output (CO) were measured in anesthetized larvae
      of Xenopus laevis from hatching (3 mg) to the end of metamorphosis (approximately
      1 g). CO and SV were calculated from videotaped images of the intact beating
      heart. SV increased from 2.4 x 10(-3) microliters at 3 mg body mass to 7.6
      microliters at 1 g. CO increased from 0.25 microliter/min at 3 mg to 623
      microliters/min at 1 g. With use of CO, along with arterial pressures from
      another study [P.-C. L. Hou and W. W. Burggren. Am. J. Physiol. 269 (Regulatory
      Integrative Comp. Physiol. 38): R1120-R1125, 1995], peripheral resistance and
      cardiac work were also calculated. Resistance decreased rapidly from 701
      peripheral resistance units (PRU, mmHg.s.mm-3) at 3 mg body mass to 79 PRU at 20
      mg and gradually declined toward 0.9 PRU at 1 g. Cardiac work increased from 0.06
      dyn.mm at 3 mg body mass to 1.27 dyn.mm at 20 mg and then climbed sharply to 717
      dyn.mm at 1 g. The general pattern of change in hemodynamic variables (except
      heart rate) during larval development is similar in Xenopus laevis and chick
      embryos, suggesting a common pattern for hemodynamic development in vertebrate
      embryos/larvae.

PMID- 7503302
TI  - Central vascular flow patterns in the alligator Alligator mississipiensis.
AB  - Many different flow patterns have been described through the central circulation
      of crocodilian reptiles. We tested the hypothesis that the vagus nerve
      stimulation promotes right-to-left (R-L) shunting in the alligator. Flow patterns
      were investigated before and during stimulation of the intact left vagus nerve
      using three methods. 1) Atrial and aortic PO2 were measured simultaneously and
      continuously by gas probes. 2) Atrial outflows were tracked with a blood tracer
      (helium). 3) Flows were assessed with echocardiography. Four different flow
      patterns were observed before vagal stimulation: left ventricular (LV) blood
      flowed into both the right (RAo) and left (LAo) aortas, whereas right ventricular
      (RV) blood flowed only into the LAo; both aortas received a mixture of LV and RV
      blood; only LV blood perfused both aortas; and RV blood flowed into both aortas,
      but LV blood flowed only into the RAo. During vagal stimulation, both aortas
      received a mixture of LV and RV blood in half of the animals, and in the other
      half, both aortas received RV blood, but LV blood flowed only into the RAo.
      Doppler and contrast echocardiography demonstrated swirling flow in the foramen
      of Panizza and the base of the LAo during systole. These data indicate that vagal
      stimulation either maintains or produces R-L shunting, flow patterns are
      variable, and blood can swirl in the foramen of Panizza and LAo base.

PMID- 7503303
TI  - Effect of thyroid hormone replacement in iron-deficient rats.
AB  - To determine if the previously observed alterations in norepinephrine (NE)
      metabolism and resting metabolic rate in iron-deficient (ID) rats result from
      hypothyroidism, exogenous thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were
      administered to ID rats in doses sufficient to normalize the plasma
      concentrations of these hormones, whereas other ID and control (CN) rats received
      placebo treatment. Resting oxygen consumption was approximately 25% higher in ID
      than CN rats; T4 but not T3 treatment alleviated this elevated oxygen uptake. The
      NE content of interscapular brown adipose tissue (IBAT), liver, and heart was 70
      80% lower in ID than CN rats, and NE turnover in the same tissues was likewise 40
      60% lower in ID than CN rats, with no systematic effect of either T3 or T4
      treatment. Liver T(4)5'-deiodinase activity was 70% lower in ID than CN rats and
      increased with T4 but not T3 treatment. These experiments show that iron
      deficiency alters NE and energy metabolism in a way that is mostly independent of
      its effects on thyroid hormone metabolism.

PMID- 7503304
TI  - Regulation of muscle glucose transport and GLUT-4 by nerve-derived factors and
      activity-related processes.
AB  - Glucose transport and GLUT-4 were examined in muscles in which activity and nerve
      derived factors were eliminated (denervation) and in muscles in which only muscle
      activity was eliminated but in which nerve-derived factors were maintained
      [tetrodotoxin (TTX) treatment]. After 3 days of denervation, insulin-stimulated 3
      O-methylglucose transport was markedly lowered in perfused rat hindlimb muscles
      (soleus, plantaris, and red and white gastrocnemius; < or = 35%). GLUT-4 was also
      decreased by 11-65% in denervated muscles. Blocking muscle activity with TTX
      superfusion of the sciatic nerve for 3 days reduced the insulin-stimulated
      glucose transport to the same extent as in the denervated muscles (P > 0.05).
      However, in soleus, plantaris, and red gastrocnemius muscles, GLUT-4 expression
      was reduced much less by TTX treatment than by denervation (P < 0.05). GLUT-4
      mRNA abundance was decreased in denervated muscles but not in TTX-treated
      muscles. These results suggest that muscle activity largely regulates the insulin
      signaling mechanisms of glucose transport and that nerve-derived trophic factors
      affect pretranslational events to regulate GLUT-4 expression.

PMID- 7503305
TI  - Relationships between muscle membrane lipids, fiber type, and enzyme activities
      in sedentary and exercised rats.
AB  - Insulin resistance in skeletal muscle is associated with 1) relative increases in
      the proportion of glycolytic and fast-twitch muscle fibers and decreases in the
      proportion of more oxidative fibers and 2) a higher proportion of the saturated
      fatty acids in membrane structural lipids. Exercise is known to improve insulin
      action. The aims of the current studies were 1) to investigate the relationship
      between muscle fiber type and membrane fatty acid composition and 2) to determine
      how voluntary exercise might influence both variables. In sedentary Wistar rats
      in experiment 1, increased amounts of unsaturated fatty acids were found in the
      more oxidative insulin-sensitive red quadriceps and soleus muscles, whereas
      reduced levels of polyunsaturated fatty acids were found in primarily glycolytic
      white quadriceps muscles. In experiment 2, voluntary running-wheel exercise by
      adult female rats over 45 days resulted in reduced proportions of type IIb fibers
      (P = 0.01) and increased proportions of type IIa/IIx fibers (P = 0.03) in
      extensor digitorum longus muscle. The magnitude of these changes was related to
      the distance run (r = -0.73, P = 0.04; r = 0.79, P = 0.02, respectively).
      Exercise significantly increased oxidative capacity, as assessed by the
      proportion of intensely NADH-stained fibers (P = 0.0004) and citrate synthase (P
      = 0.003) and hexokinase (P = 0.04) activities. Citrate synthase activity was also
      increased by exercise in soleus muscle, where, as expected, no fiber type changes
      were detected. No significant differences in the fatty acid profile of soleus and
      extensor digitorum longus were found between groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7503306
TI  - Ontogenetic development of gut function, growth, and metabolism in a wild bird,
      the Red Jungle Fowl.
AB  - We measured the ontogeny of growth rate, food intake, metabolic rates, organ
      masses, and intestinal nutrient transporter and hydrolase activities in a wild
      bird for comparison with previous measurements of the same quantities in four
      domesticated or laboratory animals. Analysis of covariance with body mass as a
      covariate showed that body mass accounted for most of the age-related variation
      in all variables, but that age itself still had a significant effect on most
      variables. Among organs studied, the ceca exhibited the greatest mass increase
      with age. Energy intake and resting and basal metabolic rates increased with age,
      but digestive efficiency, cost of growth, and sustained metabolic scope were
      independent of age. Although intestinal brush-border glucose and proline uptakes
      and sucrase activity declined with age, the corresponding capacities increased
      with age because of compensating increases in intestinal mass. Intestinal passive
      permeability to glucose was undetectably low. Unlike the four domesticated
      animals studied to date, jungle fowl possess no intestinal reserve capacities
      (excesses of capacity over dietary nutrient intake). Cecal absorption may
      contribute significantly to glucose uptake capacity with increasing age.

PMID- 7503308
TI  - Body temperature response to IL-1 beta in pregnant rats.
AB  - Rats have an attenuated or absent febrile response to exogenous pyrogen (e.g.,
      bacterial endotoxin) near term of pregnancy. With the aim of providing insight
      into possible mechanism(s) of the altered febrile response to exogenous pyrogen,
      experiments have been carried out on 67 time-bred Sprague-Dawley rats to
      investigate the febrile response to endogenous pyrogen [i.e., interleukin-1 beta
      (IL-1 beta)]. On day 13 of gestation, intravenous injection of IL-1 beta produced
      a significant increase in body temperature with a latency of approximately 30 min
      and a duration of approximately 120 min. In contrast, on days 17 and 21 of
      gestation as well as on the day of delivery, intravenous injection of IL-1 beta
      produced significant decreases in body temperature. Thus rats do not develop
      fever in response to endogenous pyrogen near term of pregnancy but rather become
      hypothermic. The mechanism of the altered body temperature response to exogenous
      pyrogen as pregnancy proceeds remains unknown. We speculate, however, that it
      most likely lies downstream from the formation of endogenous pyrogen.

PMID- 7503307
TI  - Alterations in extracellular GABA in the ventral hypothalamus of rats in response
      to acute glucoprivation.
AB  - gamma-Aminobutyric acidergic (GABA) mechanisms in the ventral hypothalamus may be
      involved in counterregulatory responses to glucoprivic episodes. Microdialysis
      probes (1 mm) were placed into the ventromedial hypothalamus (VMH) or lateral
      hypothalamus (LHA) of male Sprague-Dawley rats 3.5 h before 2-deoxy-D-glucose (2
      DG) administration (200 mg/kg i.v.). Probes were perfused (2 ml/min) with Ringer
      solution, and samples were collected every 10 min from 30 min before to 60 min
      after 2-DG. By 30 min after 2-DG, GABA concentration in VMH dialysate increased
      in a bimodal fashion to 204 +/- 36% (P < 0.01) of baseline, and GABA
      concentration in LHA dialysate decreased to 77 +/- 4% (P < 0.01) of baseline. The
      changes in dialysate GABA concentrations occurred concurrently with the animals
      eating and returned to baseline by 60 min. When animals were denied access to
      food after 2-DG, the decrease in LHA GABA was not apparent and VMH GABA remained
      approximately 15% above baseline at the end of the sample period. The results of
      the present study provide evidence that GABAergic systems in the ventral
      hypothalamus are responsive to alterations in glucose status.

PMID- 7503309
TI  - No effect of aging on skeletal muscle insulin-like growth factor mRNAs.
AB  - This study examined the hypothesis that during aging insulin-like growth factor
      (IGF) mRNAs are reduced in skeletal muscle. IGF-I, IGF-II, and IGF-binding
      protein-5 (IGFBP-5) mRNAs were measured with a ribonuclease protection assay in
      the gastrocnemius of specific pathogen-free Fischer-344 rats. We hypothesized
      that IGF-I, IGF-II, and IGFBP-5 mRNA concentration (normalized to 18S RNA) in the
      gastrocnemius muscle of growing animals (3 mo) would be downregulated in a
      coordinated manner with muscle size during aging-associated atrophy. As indicated
      by muscle wet weight and total protein content, the gastrocnemius muscle was
      growing in the 3-mo group (P < 0.01 smaller compared with 12 mo), fully developed
      at 12 mo, and was atrophied at 24 mo of age (P < 0.05 compared with 12 mo). IGF-I
      mRNA concentration in the gastrocnemius of 12- and 24-mo-old rats was 39-49% less
      than in 3-mo-old rats (P < 0.05). Contrary to our hypothesis, there was not a
      significant skeletal muscle IGF-I mRNA difference between middle age (12 mo) and
      senescence (24 mo). Thus IGF-I mRNA changed during maturation (3-12 mo) but not
      during aging (12-24 mo). Skeletal muscle IGF-II mRNA concentration was not
      different among 3-, 12-, and 24-mo-old animals. Furthermore, animal age did not
      have an effect on IGFBP-5 mRNA concentration. We conclude that the aging
      associated atrophy of skeletal muscle is not caused by altered pretranslational
      regulation of IGF-I, IGF-II, or IGFBP-5 in skeletal muscle.

PMID- 7503310
TI  - ANG II receptor blockade and arterial baroreflex regulation of renal nerve
      activity in cardiac failure.
AB  - In cardiac failure, efferent renal sympathetic nerve activity (ERSNA) and the
      activity of the renin-angiotensin system are increased, and arterial baroreflex
      regulation of ERSNA is attenuated. We examined the effect of intravenous and
      intracerebroventricular angiotensin II AT receptor blockade with losartan on the
      arterial baroreflex regulation of ERSNA in conscious control (C) and congestive
      heart failure (CHF) rats. Intravenous losartan (10 mg/kg, 21.7 mumol/kg)
      decreased arterial pressure more in CHF than in C rats (-28 +/- 3 vs. -20 +/- 3
      mmHg, P < 0.05). After restoration of arterial pressure to the prelosartan value
      with methoxamine infusion, ERSNA was decreased more in CHF than in C rats (-23 +/
      4 vs. -1 +/- 2%, P < 0.05). Maximal gain of arterial baroreflex control of ERSNA
      (Gmax) was lower in CHF compared with C rats (-1.94 +/- 0.10 vs. -3.78 +/-
      0.21%/mmHg, P < 0.05). Intravenous losartan increased Gmax in CHF (to -3.01 +/-
      0.14%/mmHg, P < 0.05) but not in C rats (to -3.56 +/- 0.19%/mmHg).
      Intracerebroventricular losartan (4.61 micrograms, 10 nmol) did not affect
      arterial pressure but decreased ERSNA more in CHF than in C rats (-13 +/- 2 vs. 
      8 +/- 3%, P < 0.05). Like intravenous losartan, intracerebroventricular losartan
      increased Gmax in CHF (from -2.11 +/- 0.18 to -3.21 +/- 0.30%/mmHg, P < 0.05) but
      not in C rats (from -3.98 +/- 0.25 to -3.84 +/- 0.22%/mmHg). These results
      suggest that increased activity of the renin-angiotensin system contributes to
      the increase in ERSNA and its abnormal arterial baroreflex regulation in cardiac
      failure.

PMID- 7503311
TI  - Antegrade and retrograde fluid transport through the vas deferens.
AB  - Intraluminal pressure of the seminal tract at seminal emission from the
      ejaculatory duct and the mode of transport of cauda epididymal contents were
      investigated to explore the mechanism of sperm transport. Direct electrical
      stimulation of any site of the cauda epididymis and vas deferens, which generated
      nerve-transmitted muscle contraction, caused elevation of the intraluminal
      pressure only at the cauda epididymis, whereas stimulation of the testis, caput,
      and corpus epididymis caused no response. The dye instilled in the cauda was
      emitted into the urethra during the stimulation. Shortly after discontinuation of
      the stimulation, retrograde movement of residual dye in the vas resulted in its
      ultimate reentry into the cauda epididymis. Significant decrease of the muscle
      tonus just after contraction was observed at the cauda. Distension of the wall of
      the vas generated elevation of the intraluminal pressure only at the site
      distended. The above results indicate the presence of rapid antegrade and
      retrograde movement of the sperm and the crucial role of the cauda epididymis on
      the sperm transport.

PMID- 7503312
TI  - Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by
      tumor necrosis factor.
AB  - The purpose of the present study was to determine 1) whether exogenous
      administration of tumor necrosis factor-alpha (TNF-alpha) alters insulin-like
      growth factor-I (IGF-I) and IGF-binding proteins (BPs) and 2) whether the
      enhanced endogenous production of TNF mediates the lipopolysaccharide (LPS)
      induced changes in the IGF system. The overnight infusion of murine TNF-alpha
      reduced circulating concentrations of both growth hormone (GH) and IGF-I in
      fasted rats. Furthermore, TNF-alpha decreased IGF-I content in liver,
      gastrocnemius muscle, and pituitary. In contrast, TNF-alpha increased IGF-I
      content in kidney and brain. IGFBP-1 was increased in plasma, liver, and muscle
      in response to TNF-alpha. In a second study, rats were injected with LPS after
      treatment with a neutralizing anti-TNF antibody (Ab), and blood and tissues were
      collected 4 h later. In LPS-treated rats, plasma concentrations of GH and IGF-I
      were reduced. LPS also decreased the IGF-I content in liver and skeletal muscle
      and increased plasma, liver, and muscle concentrations of IGFBP-1. Pretreatment
      with anti-TNF Ab attenuated the LPS-induced reduction in IGF-I and the increased
      IGFBP-1 in plasma and liver and completely prevented the decrease in IGF-I
      observed in muscle. In contrast, the LPS-induced decrease in plasma GH and the
      increased IGFBP-1 observed in muscle were unaltered by the anti-TNF Ab.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7503313
TI  - Causes of differences in respiration rate of hepatocytes from mammals of
      different body mass.
AB  - Resting O2 consumption of hepatocytes isolated from mammals ranging in mass from
      20-g mice to 200-kg horses decreases with increasing body mass. The substrate
      oxidation system increases in activity with increasing body mass and
      mitochondrial proton leak and phosphorylation system decrease in activity,
      resulting in a higher mitochondrial membrane potential in hepatocytes from larger
      mammals. The absolute rates of O2 consumption due to nonmitochondrial processes,
      substrate oxidation, mitochondrial proton leak, and the phosphorylation system
      decrease with increasing body mass. These decreases are due partly to a decrease
      in mitochondrial number per cell and partly to decrease in mitochondrial inner
      membrane proton leakiness and in ATP turnover by cells from larger mammals.
      Quantitatively, the proportion of total cell O2 consumption by nonmitochondrial
      processes (13%) and oxidation of substrates (87%) and the proportions used to
      drive mitochondrial proton leak (19%) and the phosphorylation system (68%) are
      the same for hepatocytes from all mammals investigated. The effect of matched
      decreases in the rates of proton leak and of ATP turnover is to keep the
      effective amount of ATP synthesized per unit of O2 consumed relatively constant
      with body mass, suggesting that the observed value is optimal.

PMID- 7503314
TI  - Dietary salt decreases cytosolic calcium in platelets from Dahl salt-sensitive
      rats.
AB  - To determine whether abnormal cellular Ca2+ handling is involved in salt-induced
      hypertension of Dahl salt-sensitive rats (DS), we investigated Ca2+ handling in
      fura 2-loaded platelets of DS and Dahl salt-resistant rats (DR) fed a high-NaCl
      (8%) or a low-NacL (0.3%) diet for 4 wk from 5 wk of age. At 5 wk of age, blood
      pressure, resting cytosolic Ca2+ concentration ([Ca2+]i), the thrombin-evoked
      increase in [Ca2+]i and the size of internal Ca2+ stores of DS were comparable
      with those of DR. After 4 wk on the diets, resting [Ca2+]i of DS on high-NaCl
      diet was lower than that of DS on low-NaCl diet, and there was no effect of high
      salt intake on resting [Ca2+]i in DR. In DS, high salt intake attenuated the
      [Ca2+]i response to thrombin in the presence of external Ca2+. In contrast, the
      [Ca2+]i response to thrombin in the absence of external Ca2+ was enhanced by high
      salt intake in DS. The size of internal Ca2+ stores was increased by high salt
      intake in DS but not in DR. These data suggest that it is not obligatory for
      hypertension to be accompanied by an increase in platelet [Ca2+]i.

PMID- 7503315
TI  - Patterns of blood pressure variability in normotensive and hypertensive rats.
AB  - We sought patterns in mean arterial pressure of normotensive rats and alterations
      in chronic hypertension. Pressure was recorded for 4-6 days by telemetry from
      conscious, unrestrained rats and sampled digitally at 3 Hz, using normotensive
      Sprague-Dawley rats, spontaneously hypertensive rats (SHR), and Sprague-Dawley
      rats with two-kidney, one-clip renovascular hypertension (2K,1C). Time series
      analysis was by fast Fourier transform. Power spectra were divided into ultradian
      (frequencies > 1/day), circadian (frequency = 1/day), and infradian (frequencies
      < 1/day) domains. In the ultradian band from approximately 0.1 to 10 mHz the
      spectra were 1/f and without distinct peaks. The slopes were not significantly
      different among the groups and ranged from -1.03 to -1.61. At frequencies > 10
      mHz, power continued to decrease but with a lower slope. A peak centered at
      approximately 100 mHz was present in both normotensive and 2K,1C rats but not in
      SHR. SHR had significantly more ultradian power than the others. The circadian
      rhythm modulated power in the ultradian band. Modulation was most prominent in
      normotensives, in which the ultradian activity was highest during the night when
      rats are active and lowest during the day; less pronounced in 2K,1C; and not
      detectable in SHR. There are regular patterns of blood pressure fluctuations and
      specific modifications to the patterns by different forms of hypertension.

PMID- 7503316
TI  - Neuronal discharge of preoptic/anterior hypothalamic thermosensitive neurons:
      relation to NREM sleep.
AB  - Thermosensitive neurons of the preoptic/anterior hypothalamic area (POAH) have
      been implicated in the regulation of non-rapid eye movement (NREM) sleep. We
      attempted to identify those medial POAH thermosensitive neurons that may be
      involved in NREM sleep regulation. The thermosensitivity of medial POAH neurons
      was studied in five freely moving adult cats by local cooling or warming of the
      medial POAH with a water-perfused thermode. Of 308 neurons, 65 (21%) were
      classified as thermosensitive, including 31 (10%) warm-sensitive and 34 (11%)
      cold-sensitive neurons. The spontaneous discharge rates of 28 warm-sensitive, 34
      cold-sensitive, and 115 randomly selected thermoinsensitive neurons were recorded
      through one to three sleep-waking cycles. Patterns of spontaneous activity for
      warm- and cold-sensitive neurons were different. Of 28 warm-sensitive neurons, 18
      (64%) exhibited increased discharge rate during NREM sleep compared with waking
      (NREM/wake, > or = 1.2). This subpopulation of warm-sensitive neurons also
      exhibited significantly increased thermosensitivity when tested during NREM
      sleep. Of 34 cold-sensitive neurons, 25 (74%) discharged more slowly during NREM
      sleep compared with waking (NREM/wake, < or = 0.8). This subpopulation of cold
      sensitive neurons exhibited decreased thermosensitivity during NREM sleep. These
      results are consistent with a hypothesis that the activation of sleep-related
      warm-sensitive neurons and the deactivation of wake-related cold-sensitive
      neurons may play a key role in the onset and regulation of NREM sleep.

PMID- 7503317
TI  - Preoptic/anterior hypothalamic neurons: thermosensitivity in rapid eye movement
      sleep.
AB  - The thermosensitivity of 15 warm-sensitive neurons (WSNs) and 19 cold-sensitive
      neurons (CSNs) from the medial preoptic/anterior hypothalamus (POAH) was tested
      during wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement
      (REM) sleep by local POAH warming and cooling in freely moving cats.
      Thermosensitivity was quantified by three criteria, Q10, impulses per second per
      degree Celsius, and percent change per degree Celsius. Irrespective of the
      criterion used, WSNs did not exhibit a significant change in thermosensitivity
      during REM sleep compared with wakefulness and NREM sleep. In contrast, CSNs
      exhibited decreased mean thermosensitivity during REM sleep compared with
      wakefulness. CSNs as a group did not retain significant thermosensitivity in REM
      sleep. These findings are consistent with evidence that thermoeffector responses
      to cooling are lost in REM sleep, whereas some responses to warming are
      preserved.

PMID- 7503318
TI  - Effects of swimming and environmental hypoxia on coronary blood flow in rainbow
      trout.
AB  - Previous studies have suggested that trout cardiac performance is highly
      dependent on coronary blood flow during periods of increased activity or hypoxia.
      To examine the relationship between coronary perfusion and cardiac performance in
      swimming trout, cardiac output (Q), coronary blood flow (qcor), and dorsal aortic
      blood pressure were measured in rainbow trout (Oncorhynchus mykiss) during
      normoxia and hypoxia (PO2 approximately 9 kPa). In normoxic trout, stepwise
      changes in cardiovascular variables were observed as the swimming speed was
      incrementally increased from 0.15 body lengths (bl)/s to 1.0 bl/s. At 1.0 bl/s,
      qcor and cardiac power output had both increased by approximately 110%, and
      coronary artery resistance (Rcor) had decreased by 40%. During hypoxia, resting
      qcor was 35% higher, and Rcor was 20% lower, compared with normoxic values. In
      hypoxic swimming trout, the maximum changes in qcor (155% increase) and Rcor (50%
      decrease) were recorded at 0.75 bl/s. In contrast, cardiac power output and Q
      increased by an additional 40 and 20%, respectively, as swimming speed was
      increased from 0.75 to 1.0 bl/s. The results indicate that 1) increases in qcor
      parallel changes in cardiac power output; 2) during hypoxia there are
      compensatory increases in cardiac performance and coronary perfusion; and 3) the
      scope for increasing qcor in swimming trout is approximately 150%. In addition,
      results from preliminary experiments suggest that beta-adrenergic, but not
      cholinergic, mechanisms are involved in the regulation of coronary blood flow
      during exercise.

PMID- 7503319
TI  - A wave transmission model of the umbilicoplacental circulation based on
      hemodynamic measurements in sheep.
AB  - Electrical analog models of the umbilical circulation were developed based on
      hemodynamic measurements in fetal sheep. The umbilical artery was represented by
      a transmission line and the placenta by a resistive load. Model predictions of
      input impedance and pressure and flow waveforms agreed with in vivo measurements
      under baseline conditions, following placental embolization, and during
      angiotensin II infusion. A unique positive impedance phase observed at the heart
      rate frequency under baseline conditions was best explained by the unusual
      viscoelastic properties of the umbilical arterial wall and small load
      reflections. Furthermore, a short, less vasoactive segment of the umbilical
      artery in the retroperitoneal space had a large impact on the input impedance of
      the umbilical circulation, which was particularly apparent when the artery was
      constricted during angiotensin II infusion. The model indicated that reflections
      arising near the approximate location where the first arterial branches leave the
      main umbilical artery have a measurable impact on impedance spectra when load
      reflections are low.

PMID- 7503320
TI  - Selective vagal rhizotomies: a new dorsal surgical approach used for intestinal
      deafferentations.
AB  - We have developed a dorsal intracranial surgery that is minimally invasive and
      gives excellent access to either afferent or efferent vagal rootlets to produce
      selective deafferentations or deefferentations in the rat. We have combined this
      new unilateral afferent rhizotomy with a contralateral celiac branch cut (to
      completely deafferent the intestines) and a duodenal catheter placement 4 cm
      distal to the pylorus. Animals were maintained with 17 h/day access to a
      nutritionally complete liquid diet. Measures of first meal size, daily intake,
      and body weight before and after both surgeries indicated that animals with
      unilateral vagal deafferentiations recovered as fast and completely as sham
      operated controls. Intraduodenal oleate (1.2 kcal) infusions reduced the size of
      the first meal in surgical controls (by 64%; P < 0.01) but not in the
      deafferented rats. A dual wheat germ agglutinin-horseradish peroxidase/Fluorogold
      protocol provides verification of sensory and motor lesions. The selective vagal
      deafferentation provided by the new surgery offers a useful model for determining
      gastrointestinal sites of nutrient detection and separating pre- and
      postabsorptive consequences of a meal.

PMID- 7503321
TI  - Cardiovascular and neurohormonal effects of intravenous adrenomedullin in
      conscious rabbits.
AB  - Adrenomedullin is a vasodilative peptide and shows slight homology with
      calcitonin gene-related peptide. In the present study, we investigated the
      effects of adrenomedullin on cardiovascular and neurohormonal responses in 13
      conscious rabbits. The animals were chronically instrumented with bipolar
      electrodes on the left renal sympathetic nerve. Intravenous administration of
      human adrenomedullin (10, 100, 1,000, and 3,000 pmol/kg, n = 6) caused a dose
      dependent reduction in mean arterial pressure (0 +/- 2, -1 +/- 2, -19 +/- 2, and 
      29 +/- 4 mmHg, respectively) concomitant with increases in heart rate, renal
      sympathetic nerve activity, plasma renin activity, and plasma norepinephrine. The
      significant reduction in mean arterial pressure induced by 1,000 pmol/kg of
      adrenomedullin occurred within 1 min after injection and lasted for 15 min (n =
      7). In contrast, the significant increases in heart rate and renal sympathetic
      nerve activity lasted for more than 50 min. When mean arterial pressure was
      decreased by 15 mmHg by adrenomedullin, the increases in heart rate and renal
      sympathetic nerve activity were 53 +/- 8 beats/min and 78 +/- 13%, respectively,
      which were significantly smaller than those induced by intravenous injection of
      sodium nitroprusside (102 +/- 14 beats/min and 155 +/- 34%, respectively). These
      results suggest that intravenous adrenomedullin exerts a hypotensive action that
      is associated with the attenuated reflex-mediated sympathetic activation.

PMID- 7503322
TI  - Hypothalamic response to starvation: implications for the study of wasting
      disorders.
AB  - Weight loss is a potent stimulus to food intake in normal individuals. The
      persistence of anorexia in wasting disorders, therefore, implies a failure of
      this adaptive feeding response. We describe a model for the normal hypothalamic
      response to starvation composed of the stimulation of neuronal pathways that
      promote energy intake and storage coupled with the inhibition of pathways that
      exert opposing effects. This model provides a framework for investigating
      disturbances of the normal hypothalamic response to weight loss and suggests a
      specific mechanism by which cytokines contribute to wasting in acquired immune
      deficiency syndrome and other cachexic disorders.

PMID- 7503323
TI  - Circadian locomotor rhythms in aged hamsters following suprachiasmatic
      transplant.
AB  - Circadian activity rhythms that have been eliminated by lesions of the
      suprachiasmatic nucleus (SCN) can be restored by fetal SCN grafts. Partial
      lesions of the host allow simultaneous expression of both donor and host rhythms.
      Because partial SCN ablation produces characteristic changes in activity rhythms
      that are similar to those that occur with age, including shortened period,
      reduced amplitude, and fragmentation, we investigated the extent to which fetal
      SCN grafts may be expressed by an animal whose activity rhythm exhibits these age
      dependent changes. The results indicate that expression of a transplanted clock
      is possible in an unlesioned aged host. Grafts of fetal SCN into young hosts and
      cortical tissue grafts into intact aged hosts have no effect. In those aged
      animals that received SCN grafts, three patterns of expression emerged in the
      subsequent locomotor activity record: complete dominance of locomotor rhythmicity
      by the donor; relative coordination between donor and host rhythms; and
      spontaneous switching between host and donor phenotypes. The results suggest that
      the expression of rhythmicity by the grafted SCN may depend on the relative
      amplitude or strength of signals produced by the host and donor SCN.

PMID- 7503324
TI  - Thermal and behavioral effects of lipopolysaccharide and influenza in interleukin
      1 beta-deficient mice.
AB  - This study characterized body temperature (Tb), locomotor activity (Act), and
      feeding behavior under normal conditions and following injection with
      lipopolysaccharide (LPS) or inoculation with live influenza virus of transgenic
      C57/black mice deficient in interleukin-1 beta (IL-1 beta). Tb and Act in freely
      moving mice were measured by biotelemetry. Mice deficient in IL-1 beta had normal
      circadian rhythm of Tb but were less active than their control counterparts. Mice
      injected with LPS (2.5 mg/kg i.p.) responded with a prompt decrease of Tb, which
      lasted approximately 10 h, followed by a fever in which Tb reached a peak at
      approximately 24 h postinjection. There was no difference between groups in the
      early drop of Tb after the LPS; however, the 24-h peak of Tb was lower in IL-1
      beta-deficient mice. The anorexic effects of LPS and influenza infection were
      similar in both groups of mice. In mice given influenza virus (17.5 plaque
      forming units, median lethal dose), Tb and Act gradually decreased. The fall of
      Tb was smaller in the transgenic mice. The mice deficient in IL-1 beta displayed
      a higher mortality rate due to influenza infection than the control mice. We
      conclude that deficiency in IL-1 beta results in lower fever following the LPS
      injection and in impairment of the defense response to infection with influenza.

PMID- 7503325
TI  - Hepatic portal insulin antibody infusion increases, but insulin does not alter,
      spontaneous meal size in rats.
AB  - To investigate the acute effects of pancreatic insulin on spontaneous feeding in
      rats fed ad libitum, insulin or insulin antibodies were infused into the hepatic
      portal vein during the first meal of either the light or dark phase. Infusions (3
      min, 0.033 ml/min) were remotely controlled, and a computerized system recorded
      meal patterns. In separate crossover tests, 1, 2, 4, 8, and 16 mU insulin/meal
      did not affect meal size or subsequent intermeal interval (P > 0.10). In one
      test, nocturnal meal duration was decreased by 2 mU insulin/meal (19%, P < 0.05).
      Infusions of polyclonal antibodies to human insulin with in vitro rat insulin
      binding capacity of 20 or 50 mU increased the size of the first nocturnal meal by
      24 and 29% (P < 0.05), respectively. Meal duration was reliably increased only by
      the smaller antibody dose. Subsequent intermeal interval was unaffected by either
      antibody dose. The stimulatory effect of insulin antibody infusion on meal size
      indicates that antagonism of circulating insulin during meals interferes with the
      control of meal termination. Thus insulin appears to play a role in the
      physiological control of nocturnal spontaneous feeding in rats. Exogenous insulin
      may have failed to decrease meal size because of a ceiling effect.

PMID- 7503326
TI  - Pancreatic polypeptide stimulates gastric acid secretion through a vagal
      mechanism in rats.
AB  - The present study examined the effect of pancreatic polypeptide (PP) on gastric
      acid secretion. A 45-min infusion of PP was delivered into the jugular vein of
      urethan-anesthetized rats. Rat PP (100 pmol) significantly increased acid
      secretion over baseline; bilateral cervical vagotomy or peripheral atropine both
      eliminated this acid response. Neither intraperitoneal infusion nor close intra
      arterial infusion of 100 pmol PP into the gastric circulation altered acid
      secretion. These results suggest that although PP requires intact vagal reflexes
      to stimulate acid output, it does not act on afferent or presynaptic efferent
      terminals of the vagus or directly within the stomach. Given that vagal reflexes
      consist of an afferent limb, an efferent limb, and a central relay, it may be
      that the target of circulating PP lies within the central nervous system. Indeed,
      previous studies from our laboratory have shown that microinjection of PP into
      the dorsal vagal complex results in long-lasting vagal-dependent elevation of
      gastric acid secretion.

PMID- 7503327
TI  - Endothelium-dependent relaxation is depressed at the macro- and microcirculatory
      levels during sepsis.
AB  - The objective of this study was to determine whether endothelium-derived nitric
      oxide (NO) production is reduced at the macrocirculatory and microcirculatory
      levels during sepsis. To examine this, rats were subjected to sepsis by cecal
      ligation and puncture (CLP). At 5 h after CLP (i.e., midpoint of hyperdynamic
      sepsis) or sham operation, the aorta and superior mesenteric artery were
      isolated. Responses to an endothelium-dependent vasodilator, acetylcholine (ACh),
      and an endothelium-independent vasodilator, nitroglycerin (NTG), were determined.
      In additional studies, the small intestine was isolated 5 or 20 h (hypodynamic
      sepsis) after CLP. Responses to ACh and NTG were determined in the isolated
      intestine. The results indicate that endothelium-dependent relaxation in both the
      aorta and superior mesenteric artery was depressed at 5 h after CLP. In contrast,
      there was no significant difference in the relaxation induced by NTG. Moreover,
      ACh-induced vascular relaxation in the isolated small intestine decreased at 5
      and 20 h post-CLP without any significant alterations in NTG-induced relaxation.
      Since studies have shown that ACh-induced relaxation in the aorta is reduced at
      20 h after CLP, it could be concluded that endothelium-derived NO release is
      depressed during hyperdynamic and hypodynamic stages of sepsis, not only in large
      arteries, but also at the microcirculatory level.

PMID- 7503328
TI  - Cobalt exerts opposite effects on erythropoietin gene expression in rat
      hepatocytes in vivo and in vitro.
AB  - This study investigates the effects of hypoxia and of cobalt on erythropoietin
      (EPO) gene expression in hepatocytes in vivo and in vitro in neonatal, juvenile,
      and adult rats. With the use of the ribonuclease protection assay to quantify
      RNA, both hypoxia (0.1% CO or 9% O2) and cobalt (60 mg/kg) elicit production of
      increased amounts of EPO mRNA in neonatal and juvenile rat liver in vivo. In
      vitro hepatocyte EPO gene expression could be reproducibly stimulated by hypoxia
      (3% O2) but not by cobaltous chloride (50-150 microM) within 2-20 h. Conversely,
      cobalt substantially attenuated the rise of EPO mRNA levels in response to
      hypoxia. This inhibitory effect of cobalt was mimicked by zinc but not by other
      metals. CO attenuated the rise of EPO mRNA levels in vitro in response to
      hypoxia; this inhibitory effect coincided with an inhibition of total RNA
      synthesis as determined by [3H]uridine incorporation. The lack of specific
      inhibitory effects of CO and of specific stimulatory effects of cobalt on
      hepatocyte EPO gene expression in vitro suggests that a specific heme oxygen
      sensor may be less important than in hepatoma cells.

PMID- 7503329
TI  - Improving Americans' diet--setting public policy with limited knowledge.

PMID- 7503330
TI  - Jails and prisons--America's new mental hospitals.

PMID- 7503331
TI  - The need for innovation in immunization.

PMID- 7503332
TI  - Research on the effects of prenatal alcohol exposure--a new direction.

PMID- 7503333
TI  - Prison health: the breaking point.

PMID- 7503334
TI  - The defeat of health care reform: misplaced mistrust in government.

PMID- 7503335
TI  - US adults' fruit and vegetable intakes, 1989 to 1991: a revised baseline for the
      Healthy People 2000 objective.
AB  - OBJECTIVES: This study provides revised baseline data for the Healthy People 2000
      objective related to fruit and vegetable intakes, accounting for fruits and
      vegetable intakes, accounting for fruits and vegetables from all sources and
      measuring servings in a manner consistent with current dietary guidance. METHODS:
      Dietary data from 8181 adults in the US Department of Agriculture's 1989-1991
      Continuing Surveys of Food Intakes by Individuals were examined. All foods were
      disaggregated into their component ingredients; all fruit and vegetable
      ingredients were assigned specific weights to correspond to a serving as defined
      by current dietary guidance materials; and the number of servings was tallied.
      RESULTS: While mean intakes of fruits and vegetables--4.3 servings per day--were
      not far from the Year 2000 objective, only 32% of American adults' intakes met
      the objective. When more stringent standards were set either to compensate for
      higher calorie levels or to achieve the balance between fruits and vegetables
      suggested in current guidance, only 24% and 12%, respectively, met the
      recommendations. CONCLUSIONS: These results suggest a need to develop strategies
      for overcoming barriers to eating fruits and vegetables.

PMID- 7503336
TI  - The diversion of mentally ill persons from jails to community-based services: a
      profile of programs.
AB  - OBJECTIVES: A major proposal for appropriately treating persons with mental
      illnesses who have been arrested is to divert them from jail to community-based
      mental health programs. However, there are few available definitions, guidelines,
      and principles for developing effective diversion programs. The goal of this
      research was to determine the number and kinds of jail diversion programs that
      exist, how they are set up, and which types of programs are effective. METHODS:
      On the basis of information gathered during a national mail survey (n = 1263) and
      follow-up telephone survey of 115 responding jails, 18 sites were selected for on
      site interviews based on perceived effectiveness and presence of a formal
      diversion program. RESULTS: Data are presented from a national sample of jail
      diversion programs (n = 18). Key factors for developing diversion programs and
      descriptors of effective programs are presented. CONCLUSIONS: It is clear that
      controlled, longitudinal studies of these programs' effectiveness, using client
      based and organizational outcome measures, are badly needed.

PMID- 7503337
TI  - Psychosocial factors in maternal phenylketonuria: women's adherence to medical
      recommendations.
AB  - OBJECTIVES: This study identified factors predicting adherence to medical
      recommendations in maternal phenylketonuria, which can result in severe fetal
      damage. METHODS: Sixty-nine women with phenylketonuria, 68 of their
      acquaintances, and 69 women with diabetes mellitus were interviewed annually for
      5 years. A model in which each stage in the maternal phenylketonuria life cycle
      represented a treatment-related goal provided a means to assess adherence.
      RESULTS: At the stages of prevention of unplanned pregnancy, treatment
      initiation, and diet continuation throughout pregnancy, attitudes and social
      support were associated with adherence to medical recommendations. No specific
      variables were associated with outcome at reproductive decision making, but women
      with phenylketonuria were more likely to delay making a decision, resulting in
      unplanned and, hence, untreated or late-treated pregnancy. CONCLUSIONS: Women
      with phenylketonuria differed from their acquaintances and diabetic women in many
      respects, suggesting that special programs are needed. Greater emphasis on
      reproductive decision making is especially needed. Interventions that focus on
      improving social support networks and attitudes about treatment may increase
      adherence to recommendations.

PMID- 7503338
TI  - Childhood risk factors for homelessness among homeless adults.
AB  - OBJECTIVES: This effort used data from the Course of Homelessness study and
      comparative secondary data on the general population to identify negative
      childhood and family background experiences that may increase risk for adult
      homelessness. METHODS: Frequencies of negative childhood experiences were
      examined among a probability sample of 1563 homeless adults. Differences in risk
      for such experiences were calculated by sex, age cohort, and racial/ethnicity
      status. Where possible, rates of negative childhood experiences among the
      homeless were compared with the general population. RESULTS: Substantial numbers
      of this sample experienced multiple problems as children across several domains:
      poverty, residential instability, and family problems. Women and Whites
      disproportionately reported experiences suggestive of personal or family
      problems; non-Whites disproportionately reported experiences suggestive of
      personal or family problems; non-Whites disproportionately reported experiences
      suggestive of poverty. Homeless adults were at increased risk of childhood out-of
      home placement, tenure in public housing, and homelessness, but not at greater
      risk for physical abuse. Women appeared to be at greater risk for sexual abuse.
      CONCLUSIONS: The problems that homeless individuals experience as adults have
      very clear analogs in their childhoods. Vulnerability to homelessness stems from
      factors unevenly distributed across age, sex, and race/ethnicity groups.

PMID- 7503339
TI  - Tobacco information in two grade school newsweeklies: a content analysis.
AB  - OBJECTIVES: This study compared tobacco-related articles from two elementary
      school publications, Weekly Reader and Scholastic News, published in 1989 through
      1994. METHODS: Articles for grades 4 through 6 were evaluated, and the
      publications were compared with each other. Also, issues of Weekly Reader
      published after acquisition by K-III, which is owned by the firm that formerly
      owned RJR Tobacco, were compared with the earlier ones. RESULTS: Weekly Reader
      was less likely than Scholastic News to mention short-term consequences of
      smoking (32% vs 64%) or to give a clear "no-use" message (35% vs 79%). Weekly
      Reader was more likely to give the tobacco industry position (68% vs 32%). Post-K
      III issues of Weekly Reader were less likely to provide a clear no-use message
      than earlier ones (62% vs 24%). CONCLUSIONS: Health professionals need to monitor
      the health information carried in these publications, which reach between 1 and 2
      million students per grade level each week. Although neither publication had
      perfect tobacco coverage, Scholastic News was significantly better than Weekly
      Reader.

PMID- 7503341
TI  - New York City's 1993 child immunization day: planning, costs, and results.
AB  - OBJECTIVES: This study evaluates New York City's Child Immunization Day (1993),
      with emphasis on the cost and effects of a mass campaign and the use of
      strategies from developing nations in an inner-city context. METHODS: The
      methodology was designed to (1) document the planning and implementation process,
      (2) analyze the number and characteristics of children in the target group, and
      (3) estimate costs. RESULTS: Neither the social mobilization nor the political
      will that characterize successful campaigns in developing nations occurred in New
      York City's campaign. Despite substantial time and effort from both private and
      public agencies, turnout for the event was low. In total, 2647 families and 5237
      children were assessed for health care and insurance needs, 2949 children were
      immunized at a cost of about $279 per immunized child, and 7236 vaccines were
      administered. CONCLUSIONS: The differences between inner cities and developing
      nations have a bearing on strategies used in planning and implementing mass
      campaigns. New strategies need to be forged from a blending of these contexts to
      create effective campaigns in industrialized inner cities.

PMID- 7503340
TI  - Moderate prenatal alcohol exposure and psychomotor development at preschool age.
AB  - OBJECTIVES: This study investigated the effect of moderate prenatal alcohol
      exposure on psychomotor development of preschool-age children in a longitudinal
      study. METHODS: Pregnant women were interviewed about their alcohol consumption
      at their first visit to the maternity hospital in Roubaix, France. Alcohol
      consumption before pregnancy and during the first trimester was assessed with a
      structured questionnaire. The psychomotor development of 155 children of these
      women was assessed with the McCarthy scales of children's abilities when the
      children were about 4 1/2 years old. RESULTS: Consumption of 1.5 oz of absolute
      alcohol (approximately three drinks) or more per day during pregnancy was
      significantly related to a decrease of 7 points in the mean score on the general
      cognitive index of the McCarthy scales, after gender, birth order, maternal
      education, score for family stimulation, family status, maternal employment,
      child's age at examination, and examiner were controlled for. CONCLUSIONS: This
      study showed that moderate to heavy alcohol consumption during pregnancy, at
      levels well below those associated with fetal alcohol syndrome, has effects on
      children's psychomotor development.

PMID- 7503342
TI  - A model for estimating the impact of changes in children's vaccines.
AB  - OBJECTIVES: To assist in strategic planning for the improvement of vaccines and
      vaccine programs, an economic model was developed and tested that estimates the
      potential impact of vaccine innovations on health outcomes and costs associated
      with vaccination and illness. METHODS: A multistep, iterative process of data
      extraction/integration was used to develop the model and the scenarios. Parameter
      replication, sensitivity analysis, and expert review were used to validate the
      model. RESULTS: The greatest impact on the improvement of health is expected to
      result from the production of less reactogenic vaccines that require fewer
      inoculations for immunity. The greatest economic impact is predicted from
      improvements that decrease the number of inoculations required. CONCLUSIONS:
      Scenario analysis may be useful for integrating health outcomes and economic data
      into decision making. For childhood infections, this analysis indicates that
      large cost savings can be achieved in the future if we can improve vaccine
      efficacy so that the number of required inoculations is reduced. Such an
      improvement represents a large potential "payback" for the United States and
      might benefit other countries.

PMID- 7503343
TI  - The tracking of nutrient intake in young children: the Framingham Children's
      Study.
AB  - OBJECTIVES: This study compared the nutrient intake of children at 3 through 4
      years of age with that in subsequent years to determine whether nutrient intake
      tracked over time. METHODS: Intakes of 10 nutrients were estimated by means of
      multiple days of food diaries collected over a span of up to 6 years of follow-up
      for 95 children in the Framingham Children's Study. All diaries collected during
      each of three age periods (age 3 through 4, age 5 through 6, and age 7 through 8)
      were averaged. Nutrient density intakes at each age period were compared.
      RESULTS: Nutrient-specific correlations ranged from .37 to .63 between nutrient
      density intakes at age 3-4 and age 5-6. Correlations between intakes at age 3-4
      and age 7-8 ranged from .35 to .62. Consistency of classification was strong;
      35.7% to 57.1% of children in the highest quintile of intake at age 3-4 remained
      in that quintile at age 5-6, and 57.1% to 85.7% remained in the top two
      quintiles. At age 7-8, 40.0% to 66.7% of those with the highest intake at
      baseline were still in the top quintile, and 60.0% to 93.3% remained in the top
      two quintiles. Results were similar in the lowest quintile of intake. Extreme
      misclassification was rare. CONCLUSIONS: This study suggests that tracking of
      nutrient intake begins as young as 3-4 years of age.

PMID- 7503344
TI  - Fluoride exposure and childhood osteosarcoma: a case-control study.
AB  - OBJECTIVES: This study tests the hypothesis that fluoride exposure in a
      nonoccupational setting is a risk factor for childhood osteosarcoma. METHODS: A
      population-based case-control study was conducted among residents of New York
      State, excluding New York City. Case subjects (n = 130) were diagnosed with
      osteosarcoma between 1978 and 1988, at age 24 years or younger. Control subjects
      were matched to case subjects on year of birth and sex. Exposure information was
      obtained by a telephone interview with the subject, parent, or both. RESULTS:
      Based on the parents' responses, total lifetime fluoride exposure was not
      significantly associated with osteosarcoma among all subjects combined or among
      females. However, a significant protective trend was observed among males.
      Protective trends were observed for fluoridated toothpaste, fluoride tablets, and
      dental fluoride treatments among all subjects and among males. Based on the
      subjects' responses, no significant associations between fluoride exposure and
      osteosarcoma were observed. CONCLUSIONS: Fluoride exposure does not increase the
      risk of osteosarcoma and may be protective in males. The protective effect may
      not be directly due to fluoride exposure but to other factors associated with
      good dental hygiene. There is also biologic plausibility for a protective effect.

PMID- 7503345
TI  - Victimization prevention programs for children: a follow-up.
AB  - OBJECTIVE: This study examined whether victimization prevention instruction in
      school has any impact on children's behavior in situations of real victimization
      threat. METHODS: Telephone interviews were conducted in 1992 with a nationally
      representative sample of youths aged 10 to 16 and their caretakers, and the
      experience of 1457 of these children was followed up more than a year later.
      RESULTS: Exposure to a more comprehensive prevention program was not associated
      with reduced incidence of victimization, injury, or upset. However, some of the
      exposure conditions were associated with an increased likelihood that the
      children would disclose victimizations, an increased likelihood that they would
      see themselves as having successfully protected themselves, and a decreased
      likelihood that they would blame themselves for the episode. Exposed children
      acquired some knowledge about sexual abuse and, when actually confronted by a
      threat, an ability to do the things they had been taught. A nonsignificant trend
      was also noted toward increased injury for exposed children during sexual
      assaults. CONCLUSION: These mixed findings suggest that prevention educators need
      to plan programs based on realistic goals for what can be accomplished.

PMID- 7503346
TI  - The availability of low-fat milk in an inner-city Latino community: implications
      for nutrition education.
AB  - Substitution of low-fat for whole milk is an important strategy for reducing
      saturated fat consumption, but intake of whole milk remains high among Latinos.
      To assess whether this is related to the unavailability of low-fat milk, we
      surveyed 251 grocery stores (bodegas) and 25 supermarkets in a predominantly low
      income, urban Latino community. Low-fat milk was available in 73% of bodegas and
      96% of supermarkets, but it constituted only 15% of total milk volume in bodegas
      and 37% of that volume in supermarkets. Since lack of availability was not a
      major obstacle to increasing low-fat milk consumption, public health nutrition
      campaigns should focus on increasing consumer demand.

PMID- 7503347
TI  - Inhaled and oral corticosteroids: their effects on bone mineral density in older
      adults.
AB  - Use of oral and inhaled corticosteroids and bone mineral density were examined
      cross-sectionally in 1673 community-dwelling white subjects aged 56 to 91 years.
      Bone mineral densities at the ultradistal and midshaft radii, hip, and lumbar
      spine were compared in users of inhaled (n = 34) and oral (n = 44)
      corticosteroids and nonusers. Women who used oral corticosteroids had
      significantly lower bone mineral densities at the midshaft radius, hip, and spine
      than never users. Women who used inhaled corticosteroids had bone mineral
      densities at the ultradistal radius, hip, and spine that were intermediate
      between those of oral corticosteroid users and those of never users. Bone mineral
      density did not vary significantly according to corticosteroid use in men.

PMID- 7503348
TI  - Changes in perinatal cocaine use in an inner-city hospital, 1988 to 1992.
AB  - Temporal trends in perinatal drug use among parturients at an inner-city hospital
      were assessed in a cohort study of 1300 parturients in 1991 through 1992 and 1111
      parturients in 1988 through 1989. Toxicology results were coupled to data sheets
      containing demographic and obstetrical information. A decrease was noted between
      1988 and 1992 in the prevalence of cocaine metabolites, independent of the
      utilization of prenatal services. An increase in marijuana use and no change in
      opiate use were seen. When adjusted for ethnicity and receipt of care, a 50%
      decline in the odds ratio (OR) of cocaine use was noted between 1988 and 1992 (OR
      = 0.55; 95% confidence interval = 0.39, 0.79).

PMID- 7503350
TI  - Aerobic fitness, blood lipids, and body fat in children.
AB  - This study examined the association between aerobic fitness and serum cholesterol
      and the effects of controlling for gender, body composition, abdominal fat, and
      dietary saturated fat in 262 children. The 1-mile run was used to estimate
      fitness. Skinfolds were used in assessing body fat. Fit children had lower total
      cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and
      higher high-density lipoprotein cholesterol levels than unfit children, except
      after adjustment for body fat and/or abdominal fat. Unfit children appear to be
      at an increased risk of unhealthy levels of serum cholesterol due primarily to
      increased levels of body fat.

PMID- 7503352
TI  - Teaching and reinforcing hygienic practices in child care centers.

PMID- 7503351
TI  - The reporting sensitivities of two passive surveillance systems for vaccine
      adverse events.
AB  - To evaluate reporting sensitivities for vaccine adverse events, reporting rates
      were estimated by dividing the number of events reported to the Monitoring System
      for Adverse Events Following Immunization and the Vaccine Adverse Event Reporting
      System in a given period by the number of doses administered or distributed
      during the same period. Reporting sensitivity was calculated as the ratio of the
      rates at which events were reported to each passive surveillance system
      (numerator) and occurred in controlled studies (denominator). Reporting
      sensitivities were generally better in the public sector than in the private
      sector. The significant underreporting of known outcomes, together with the
      nonspecific nature of most adverse event reports, highlights the limitations of
      passive surveillance systems in assessing the incidence of vaccine adverse
      events.

PMID- 7503349
TI  - Correlates of high-density lipoprotein cholesterol in Black girls and White
      girls: the NHLBI Growth and Health Study.
AB  - To determine the correlates of serum high-density lipoprotein cholesterol (HDL-C)
      in 9- and 10-year-old girls, data were examined from 624 Black girls and 773
      White girls. Black girls had, on average, 3.6 mg/dL higher levels than White
      girls. Each 10-mm increase in sum of skinfolds was associated with a decrease of
      1.4 mg/dL; each unit increase in the tricep/suprailiac skinfold ratio was
      associated with an increase of 2 mg/dL; and each 10% increase in polyunsaturated
      fat intake was associated with an increase of 3.4 mg/dL. The associations of
      sedentary activity and sexual maturation with HDL were mediated by differences in
      adiposity. Interventions to decrease adiposity may be important for the primary
      prevention of heart disease in women.

PMID- 7503353
TI  - Causes of death in Florida prisons: the dominance of AIDS.

PMID- 7503354
TI  - The reliability of cigarette consumption reports by spousal proxies.

PMID- 7503355
TI  - Is public health credentialing necessary?

PMID- 7503356
TI  - Endometrioid carcinoma of the ovary with a prominent spindle-cell component, a
      source of diagnostic confusion. A report of 14 cases.
AB  - Fourteen endometrioid carcinomas of the ovary with a prominent component of
      spindle-shaped epithelial cells are reported. Eleven were initially misdiagnosed
      as sexcord stromal tumors, malignant mesodermal mixed tumors, tumors of probable
      wolffian origin, or metastatic carcinomas. All of the tumors, however, had one or
      more features establishing them as endometrioid carcinomas, including (a) glands
      typical of endometrioid adenocarcinoma, (b) foci of squamous differentiation, and
      (c) an adenofibromatous component. Six cases were examined immunohistochemically,
      and the epithelial nature of the spindle cells was supported by immunostaining
      for keratin and epithelial membrane antigen. The patients ranged in age from 42
      to 89 years (mean, 61). Four cases were stage I, five stage II, and three stage
      III. Follow-up information was available in seven cases. Five patients were free
      of disease at 8, 11, 32, 56, and 103 months, and two patients were alive with
      disease at 10 and 20 months. The age of the patients, clinical presentation,
      tumor stage, and gross appearance were similar to those of typical endometrioid
      carcinomas. It is important that this tumor be distinguished from other ovarian
      neoplasms with a spindle-cell component because of differences in treatment and
      prognosis.

PMID- 7503357
TI  - Microdissection and molecular genetic analysis of HER2/neu in breast carcinoma.
AB  - Precise correlation of histomorphology with molecular genetic analysis is
      difficult in tissues composed of heterogeneous cell populations. We describe here
      a novel microdissection technique employed to correlate HER2/neu (HER2)
      immunohistochemical staining with HER2 genetic analysis in formalin-fixed,
      paraffin-embedded breast tissue. Fourteen invasive ductal carcinomas were
      selected from the pathology files of Memorial Sloan-Kettering Cancer Center that
      had been immunostained for HER2. Seven tumors showed typical membrane
      immunoreactivity and seven were negative. A dissecting microscope was then used
      to isolate minute (< or = 1 mm x 1 mm) areas of invasive carcinoma and normal
      breast tissue for molecular study. To document the type of cell sample submitted
      for polymerase chain reaction (PCR) analysis, each microdissected piece of tissue
      was photographed prior to removal from the glass slide. A preliminary study of
      four cases compared the results of PCR and genetic analysis using microdissected
      hematoxylin and eosin (H & E)-stained tissue, unstained dewaxed tissue, and
      destained dewaxed tissue in four specimens. Similar results were obtained with
      all three tissue preparations. Thereafter, H & E stained sections were selected
      as the tissue preparation of choice because tissue details were seen more
      clearly. There was complete correlation of immunohistochemical staining and HER2
      analysis by PCR in all 14 cases. In the final 10 cases, the PCR product was
      resolved by gel electrophoresis and quantified by optical densitometry. Fourfold
      to eightfold amplification of HER2 was found in the five tumor specimens that
      immunohistochemically stained for HER2. A single copy of HER2 was found in all
      HER2-negative tumors and in normal breast tissue. We conclude that it is possible
      to quantify gene amplification of HER2 in minute samples of H & E-stained normal
      and malignant breast tissue. This microdissection technique can be applied to
      correlative histologic--molecular genetic analysis in a wide variety of tumor
      types.

PMID- 7503358
TI  - Paratesticular serous papillary carcinoma. A report of six cases.
AB  - Six intrascrotal, invasive epithelial neoplasms of serous papillary type arose in
      the paratesticular region of patients 16 to 42 (mean, 30.8) years of age. Five
      patients, one with an associated hydrocele, presented with a testicular mass and
      one with a hydrocele only. The serum CA-125 level was elevated in one of the two
      patients in whom it was measured. Grossly, the tumors were solid, white, or tan,
      poorly circumscribed, often gritty masses. Four tumors involved primarily the
      soft tissue between the testis and epididymis (testiculoepididymal groove) and
      one, the paratesticular soft tissue. The sixth tumor was confined to the visceral
      tunica vaginalis at the inferior pole of the testis. The most common microscopic
      pattern was characterized by invasive, well-formed papillae lined by serous
      cuboidal or columnar cells with eosinophilic cytoplasm and malignant nuclear
      features. Psammoma bodies were abundant in all the cases. Areas of borderline
      serous tumor were present in two tumors and predominated in one. Five of five
      tumors were positive for keratin (AE1/3), S-100, epithelial membrane antigen, and
      Ber-EP4; three of five for Leu M1 and B72.3; two of five for carcinoembryonic
      antigen and placental alkaline phosphatase; and one in five for vimentin.
      Ultrastructural examination in one case demonstrated gland formation with
      delicate luminal microvilli and cilia. Follow-up information was available in
      five cases: Three patients are without evidence of disease after relatively short
      postoperative intervals of 1, 1, and 3 years, although one of these patients has
      had a persistently elevated CA-125 level. Two patients had recurrence of their
      tumors 4 and 7 years after diagnosis, one with diffuse abdominal spread, the
      other in a cervical lymph node. The latter patient died of his disease 5 years
      after diagnosis.

PMID- 7503359
TI  - Involvement of collagenous spherulosis by lobular carcinoma in situ. Potential
      confusion with cribriform ductal carcinoma in situ.
AB  - We describe five cases in which the cells of lobular carcinoma in situ seemed to
      form round, regular lumens similar to the cribriform spaces of ductal carcinoma
      in situ. After careful inspection, we concluded that the spaces indicate the
      presence of collagenous spherulosis and that this unusual pattern arises through
      the confluence of lobular neoplasia and spherulosis. We base this conclusion on
      three lines of evidence. First, attenuated myoepithelial cells, rather than
      carcinoma cells, form the spaces in question. Immunohistochemical staining for
      smooth-muscle actin and keratin 8/18 established the myoepithelial nature of
      these flattened cells because they express the former protein but lack the
      latter. These results also differentiate the myoepithelial cells from those of
      conventional in situ carcinomas, which do not contain smooth-muscle actin but
      virtually always possess keratin 8/18. Second, the material within the spaces
      looks like the deposits that characterize collagenous spherulosis. They consist
      of densely eosinophilic protein or radiating, fibrillar ground substances, and
      they differ in appearance from the disorganized, flocculent mucin and the
      cellular debris found in some in situ ductal carcinomas. Finally, the neoplastic
      cells display a loosely cohesive growth pattern that is more in keeping with the
      properties of lobular neoplasia than ductal carcinoma. Considered together, these
      three points should distinguish involvement of collagenous spherulosis by lobular
      neoplasia from cribriform ductal carcinoma in situ. Pathologists must remain
      alert to this form of mimicry because classification of in situ carcinoma of the
      breast carries important clinical implications.

PMID- 7503360
TI  - Pancreatoblastoma. A clinicopathologic study and review of the literature.
AB  - Pancreatoblastoma is a rare pancreatic tumor with a distinctive histologic
      appearance that generally affects infants and young children. We have studied 14
      cases of pancreatoblastoma and reviewed 41 previously reported examples. Nine of
      our cases occurred in children (from newborn to 4 years old; mean, 2.4), and five
      affected adults (from 19 to 56 years old; mean, 40). There were 8 male cases and
      6 female cases. Most patients presented with incidental abdominal masses,
      although pain, weight loss, and obstructive jaundice were present, but rarely.
      The tumors were very cellular microscopically, with cytologically uniform
      epithelial cells arranged in sheets and nests. Well-formed acinar structures were
      a consistent feature, and several cases contained ectatic ductular formations,
      rarely exhibiting intracellular mucin. Consistently present were squamoid
      corpuscles: circumscribed, whorled nests of plump spindle cells with a squamous
      appearance and occasional keratinization. The stroma was moderate to abundant and
      frequently quite cellular (especially in the pediatric cases). By
      immunohistochemistry, the tumors exhibited acinar, endocrine, and ductal
      differentiation, with positivity for pancreatic enzymes (100%), endocrine markers
      (82%), and carcinoembryonic antigen (85%). Ultrastructural examination most
      commonly revealed acinar differentiation, although mucigen granules and
      neurosecretory granules were also occasionally found. The behavior was variable:
      36% of patients developed metastases, especially to the liver. The adult patients
      did poorly: three of five died of tumor (mean survival, 18 months), and two were
      alive at 5 and 15 months, respectively. In contrast, five of the six evaluable
      pediatric patients were alive from 22 months to 22 years after diagnosis, and
      only one died of tumor after 16 months. Good responses to chemotherapy were noted
      in the pediatric group.

PMID- 7503361
TI  - Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A
      clinicopathologic analysis of 109 cases with emphasis on distinguishing
      pathologic features, site of origin, prognosis, and relationship to "pseudomyxoma
      peritonei".
AB  - Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by
      mucinous ascites and mucinous implants diffusely involving the peritoneal
      surfaces. There is considerable debate regarding the definition, pathology, site
      of origin, and prognosis of PMP. We analyzed the clinicopathologic features of
      109 cases of multifocal peritoneal mucinous tumors to develop a pathologic
      definition of cases characterized by the clinical condition PMP. Cases were
      separated into two diagnostic categories: disseminated peritoneal adenomucinosis
      (DPAM) and peritoneal mucinous carcinomatosis (PMCA). Cases classified as DPAM
      were characterized by peritoneal lesions composed of abundant extracellular mucin
      containing scant simple to focally proliferative mucinous epithelium with little
      cytologic atypia or mitotic activity, with or without an associated appendiceal
      mucinous adenoma. Cases classified as PMCA were characterized by peritoneal
      lesions composed of more abundant mucinous epithelium with the architectural and
      cytologic features of carcinoma, with or without an associated primary mucinous
      adenocarcinoma. Sixty-five of the 109 cases (59.6%) were classified as DPAM
      consistent with origin from an appendiceal mucinous adenoma. Thirty-seven of the
      65 cases (56.9%) had a documented appendiceal mucinous adenoma. Thirty cases
      (27.5%) were classified as PMCA consistent with origin from an appendiceal or
      intestinal mucinous adenocarcinoma. Fourteen cases (12.8%) were classified as
      PMCA with features intermediate between DPAM and PMCA or with discordant features
      based on the finding of at least focal areas of carcinoma in the peritoneal
      lesions, whether or not the primary site demonstrated carcinoma. The cases with
      intermediate features were derived from well-differentiated appendiceal or
      intestinal mucinous adenocarcinomas and had peritoneal lesions displaying
      features of DPAM as well as focal areas of mucinous carcinoma. The cases with
      discordant features were derived from atypical appendiceal adenomas with little
      or no histologic evidence of a transition from adenoma to carcinoma and had
      peritoneal lesions uniformly composed of mucinous carcinoma. There was a
      statistically significant difference in survival between cases classified as
      DPAM, those classified as PMCA with intermediate or discordant features, and
      those classified as PMCA (p < 0.0001). The age-adjusted 5-year survival rates
      were 84% for patients with DPAM, 37.6% for patients with PMCA with intermediate
      or discordant features, and 6.7% for patients with PMCA. The term DPAM should be
      used to diagnose the histologically benign peritoneal lesions associated with
      ruptured appendiceal mucinous adenomas and those that are pathologically
      identical but lack a demonstrable appendiceal adenoma. Cases with the pathologic
      features of adenocarcinoma should be designated PMCA because they have
      recognizably different pathologic features and a significantly worse prognosis.

PMID- 7503362
TI  - Chronic hepatitis. An update on terminology and reporting.
AB  - The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CpH), and
      chronic lobular hepatitis (CLH) have become obsolete, and their use without
      further specifications should be discontinued. This recommendation has become
      necessary because these names have changed from descriptive terms, intended for
      grading, to terms that are used either as morphologic diagnoses or disease
      designations or both, depending on individual preferences. Because this practice
      has caused serious misunderstandings, many authors and two international groups
      have recommended the use of a clear etiologic terminology. For the reporting
      practice of pathologists, we recommend that the pathologist routinely sign out
      biopsy samples with features of chronic hepatitis by indicating etiology, grade,
      and stage. An example would be autoimmune hepatitis, severe, stage 3. The stage
      in this case would indicate the presence of well-developed septal fibrosis but no
      nodular regeneration. Obviously, for the etiologic diagnosis, morphologic
      findings must be integrated with clinical and laboratory data. If this
      information is not available, clear morphologic diagnoses should be reported.
      Thus, instead of CPH, the diagnosis should be portal hepatitis, cause
      undetermined. This reporting practice eliminates ambiguous terminology and avoids
      the risk of inappropriate treatment as might occur, for example, when a term such
      as CAH is used to describe Wilson's disease and is misunderstood to mean
      autoimmune hepatitis. For a transitional period and to facilitate relearning, the
      terms CAH, CPH, and CLH can be reported in parentheses behind the etiologic
      diagnosis.

PMID- 7503363
TI  - p53 overexpression in the multistep process of esophageal carcinogenesis.
AB  - The timing of p53 mutation in the multistep process of esophageal carcinogenesis
      is still under debate. We tested p53 expression in 16 samples of low-grade and 29
      samples of high-grade esophageal dysplasia (ED) coexisting with esophageal
      squamous cancer (ESC) in 31 patients who underwent total esophagectomy. In normal
      mucosa, a positive immunoreaction was detected in 10 of 31 cases, always
      restricted to the lower half of the epithelial thickness. We detected p53
      positive nuclei in 11 of 16, 23 of 29, and 23 of 31 samples of low-grade ED, high
      grade ED, and ESC, respectively. Cases exhibiting positive staining in dysplastic
      samples also demonstrated positive immunoreaction in the carcinomatous tissue.
      Immunoreactivity in cancer cells was never found in the absence of positive
      dysplastic nuclei. A significantly higher score of immunoreactive nuclei was
      detected in high-grade versus low-grade and in low-grade compared with normal
      mucosa. These data suggest that p53 mutation may represent an early event in
      esophageal oncogenesis.

PMID- 7503364
TI  - Reassessment of histologic parameters in the diagnosis of mycosis fungoides.
AB  - The histologic diagnosis of mycosis fungoides (MF) can be difficult to establish
      and is based on interpretation of numerous subtle changes, most of which may be
      present to some degree in many inflammatory and neoplastic cutaneous conditions.
      To reassess the diagnostic criteria for making a histologic diagnosis of MF, we
      retrospectively reviewed histologic sections from 64 patients with mycosis
      fungoides (MF+) and compared the findings with sections from 47 patients who were
      biopsied to exclude MF and were shown not to have the disease (MF-). Patients
      were selected as MF+ or MF- independent of histologic findings based on the
      clinical course with at least 3 years of follow-up and immunophenotyping results.
      Following patient selection, at least two observers reviewed each slide without
      knowledge of final diagnosis and graded the intensity of approximately 25
      histologic parameters. On univariate analysis, the following parameters were
      significant at beyond the p = 0.01 level: Pautrier's abscesses, haloed
      lymphocytes, exocytosis, disproportionate epidermotropism, epidermal lymphocytes
      larger than dermal lymphocytes, hyperconvoluted intraepidermal lymphocytes, and
      lymphocytes aligned within the basal layer. Haloed lymphocytes proved to be the
      most robust discriminator of MF from non-MF on multivariate analysis. These
      findings show that whereas many previously described features do discriminate
      between MF and inflammatory mimics, others are much less specific. Furthermore,
      few cases demonstrate all histologic features; for example, Pautrier's
      microabscesses were seen in only 37.5% of our cases. We conclude that a
      combination of specific histologic parameters can be used to establish a
      microscopic diagnosis of MF without the necessity of confirmatory
      immunophenotyping in the vast majority of cases.

PMID- 7503365
TI  - Hodgkin's disease of Waldeyer's ring. Clinical and histoimmunophenotypic findings
      and association with Epstein-Barr virus in 16 cases.
AB  - Waldeyer's ring is an uncommon, rarely reported primary site for Hodgkin's
      disease. We report a series of 16 such cases culled from the files of the Armed
      Forces Institute of Pathology and the National Cancer Institute. The patients'
      median age was 41 years (range, 14-74), and they presented with airway
      obstruction or unilateral tonsillar enlargement. The disease was localized to the
      Waldeyer's ring (stage I) in 46% of patients and extended to the cervical lymph
      nodes (stage II) in 39% and to the spleen (stage III) in 15%. Local radiation
      therapy, with or without chemotherapy, obtained a complete response in all but
      two patients. There was local recurrence in one patient and distant spread in
      three others. All patients for whom follow-up is available are alive without
      evidence of disease at 9 to 216 months (median, 20 months) except two who died of
      widespread Hodgkin's disease and two others who died of other causes.
      Histologically, eight cases were classified as mixed cellularity type (50%), four
      as nodular sclerosis (25%), and one as lymphocyte predominance, nodular (LPn;
      6.3%); three others that showed interfollicular involvement were unclassified
      (18.7%). The Reed-Sternberg (RS) and atypical mononuclear cells in most cases of
      mixed cellularity and interfollicular types and all cases of nodular sclerosis
      had the classic immunophenotype (CD45-, CD20- and/or CD45RO-, CD15+ and/or
      CD30+). In the single case of LPn, they were of B-cell lineage (CD45+, CD20+,
      CD45RO-, CD15-, CD30-). In situ hybridization performed on routinely processed
      sections revealed Epstein-Barr virus (EBV) EBER1 mRNA in RS cells of eight of 12
      cases studied (67%) only in mixed cellularity and nodular sclerosis, but not in
      LPn. We conclude that, however rarely, Hodgkin's disease of typical morphology
      and immunophenotype can originate in Waldeyer's ring. The incidence of EBV
      detection in the RS cells in our study is greater than that usually seen in nodal
      Hodgkin's disease in the United States. The greater prevalence of EBV-related
      Hodgkin's disease at this site is probably a reflection of the fact that the
      Waldeyer's ring is a reservoir for EBV.

PMID- 7503366
TI  - Postcaesarean section uterovesical fistula lined by persistent intermediate
      trophoblast.
AB  - We report a unique case of a postcaesarean section uterovesical fistula lined by
      intermediate trophoblast. The patient, a 42-year-old woman, presented with
      cyclical haematuria, and she had had a lower segment caesarean section 1 year
      previously. She was found to have uterovesical fistula, which was excised. On
      microscopic examination the fistula tract was lined by intermediate trophoblast
      characterised by cells with abundant eosinophilic cytoplasm, occasional
      multiclefted nuclei, and cytoplasmic immunoreactivity for epithelial cytokeratins
      and human placental lactogen. This finding has not, to our knowledge, been
      previously described and indicates that the survival of third trimester
      intermediate trophoblast is independent of pregnancy.

PMID- 7503367
TI  - GIST.

PMID- 7503368
TI  - Mucus retention in heterotopic pancreas of the gastric antrum: a lesion mimicking
      mucinous carcinoma.

PMID- 7503369
TI  - Fibrocartilagenous mesenchymoma versus fibrocartilagenous dysplasia-: are these a
      single entity?

PMID- 7503370
TI  - Rationale and development of a quality-of-life instrument for head-and-neck
      cancer patients.

PMID- 7503371
TI  - Atypical presentations of aural tuberculosis.

PMID- 7503372
TI  - What is the bacteriology of chronic sinusitis in adults?
AB  - PURPOSE: Recent advances in imaging and endoscopy has increased our awareness of
      chronic sinusitis. The teaching has been that chronic sinusitis is mainly caused
      by anaerobes; however, recent studies have found that the role of anaerobes is
      small, especially in children. MATERIALS AND METHODS: A prospective study was
      conducted on 76 adults who failed medical treatment for chronic sinusitis and
      were scheduled for endoscopic sinus surgery. Specimens were obtained on all 76
      patients at the time of surgery and were sent for aerobic and anaerobic cultures.
      RESULTS: Anaerobic organisms were isolated in 7.6% of the cases, and aerobes were
      isolated in 76.3% of the patients. The most common aerobic organism was the
      Staphylococcus species, whereby resistance to the most commonly used antibiotics
      was 21.7%. CONCLUSION: All past studies on the bacteriology in adults were made
      before the era of endoscopic sinus surgery and the newer-generation antibiotics.
      According to our results, it seems there is a change in trend in the bacteriology
      of chronic sinusitis in adults.

PMID- 7503373
TI  - Identification of the external branch of the superior laryngeal nerve (EBSLN) in
      large goiters.
AB  - BACKGROUND: Intraoperative injury to the external branch of the superior
      laryngeal nerve (EBSLN) can result in significant postoperative voice problems.
      This injury can be avoided by intraoperative nerve identification. The EBSLN has
      a close anatomic relationship with the superior thyroid pedicle. According to the
      previous anatomic classification, the type 2b nerve, which crosses the vessels
      below the superior thyroid pole and is considered high risk, is found in 14% to
      20% of persons with normal or slightly enlarged thyroid glands. OBJECTIVE: To
      analyze the frequency of this type 2b nerve in a population with large goiters
      and to compare it with the previously mentioned proportions. DESIGN:
      Nonrandomized prospective study. PATIENTS AND METHODS: During a 15-month period,
      patients with large uninodular or multinodular goiters were entered in the study.
      The EBSLN was searched with the help of a nerve stimulator and the type was
      annotated. If the patient had to be submitted to a bilateral thyroidectomy, each
      superior thyroid pole, with the correspondent nerve, was considered as a separate
      unit. RESULTS: Nine patients, all women, underwent surgery. The average size of
      the goiters was 10.9 cm x 7.3 cm x 5.0 cm, and the average weight of the
      specimens was 431 g. There were four bilateral procedures, totalling 13 nerves
      analyzed. Seven (54%) were type 2b. CONCLUSION: The frequency of the type 2b
      EBSLN is considerably higher in large goiters. This finding suggests that it is
      even more advisable to try to positively identify the nerve in these situations,
      in order to prevent its injury, which is permanent and troublesome for voice
      professionals.

PMID- 7503374
TI  - Effect of topical hyaluronic acid on experimental cholesteatoma.
AB  - PURPOSE: Inflammation and connective tissue hyperplasia are believed to be
      important etiological factors in cholesteatoma pathogenesis. Previous work has
      shown that topically applied hyaluronic acid can reduce connective tissue
      proliferation in healing wounds and accelerate healing of tympanic membrane
      perforations. This study was undertaken to determine whether the
      antiproliferative effect of hyaluronic acid may inhibit propylene glycol-induced
      cholesteatoma in an animal model. MATERIALS AND METHODS: A 60% propylene glycol
      solution was injected bilaterally into the middle ear cavities of 20 adult
      chinchillas. The control group (N = 10) received propylene glycol alone. In
      addition to propylene glycol injections, the experimental group (N = 10) received
      repeated bilateral topical applications of 1.5% hyaluronic acid onto the tympanic
      membranes. Animals were killed at 4 weeks for gross and light microscopic
      examination. RESULTS: Seven control and 10 experimental animals survived the full
      1-month study period. At the end of that time, cholesteatoma was found in 71%
      (10/14) of control ears and 70% (14/20) of experimental ears. Tympanic membrane
      structure did not differ significantly between groups by light microscopy and, in
      all animals, cholesteatomas originated by migration of hyperplastic epidermis
      through the tympanic membrane, as has been observed in previous studies using
      this animal model. CONCLUSION: Under the conditions of this study, topical
      hyaluronic acid had no significant effect on cholesteatoma formation.

PMID- 7503376
TI  - Imaging characteristics of carotid body tumors.

PMID- 7503375
TI  - Involvement of interleukin-1 in middle ear cholesteatoma.
AB  - PURPOSE: The histopathological characteristics of middle ear cholesteatoma are
      hyperproliferation and differentiation of the epithelium and accompanying
      destruction of the bones. We directed our attention to interleukin 1 alpha (IL-1
      alpha) and demonstrated localization of IL-1 alpha in the epidermis of
      cholesteatoma. In addition, a comparative study was made of the relationship of
      IL-1 alpha with the developmental stage of cholesteatoma, the degree of
      destruction of the auditory ossicles, presence/absence of otorrhea, and the state
      of subepithelium. MATERIALS AND METHODS: Middle ear cholesteatoma tissues
      collected during operations were used as the experimental material, and sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot, and
      immunohistological techniques were used as methods. RESULTS: An anti-IL-1 alpha
      antibody-positive 17-kd band was observed in 2 of the 17 cases, whereas a 31-kd
      band was observed in 10 of the 17 cases. Neither the 17-kd band nor the 31-kd
      band was detected in normal skin tissues. The immunohistological staining showed
      the presence of IL-1 alpha in a region near the basal membrane of cholesteatoma
      epithelium. CONCLUSION: A correlation was observed between IL-1 alpha and
      patients with vigorous proliferation of granulation in the subepithelium. The
      presence of granulation in the reverse side of the eardrum plays an important
      role in the proliferation of cholesteatoma epithelium.

PMID- 7503377
TI  - Radiographic evaluation of a subglottic cyst in an infant.

PMID- 7503378
TI  - Retropharyngeal liposarcoma.

PMID- 7503379
TI  - "Bleeding polyp" of the osseous nasal septum: a rarely seen lesion.

PMID- 7503380
TI  - Cystic hygroma: recurrence in an adult 34 years later.

PMID- 7503381
TI  - CO2 laser posterior transverse cordotomy for isolated type IV posterior glottic
      stenosis.
AB  - One case of isolated type IV posterior glottic stenosis successfully treated with
      CO2 laser posterior transverse cordotomy is presented. This report emphasized the
      value of the CO2 laser posterior transverse cordotomy in this situation. A review
      of the various therapeutic options advocated in the medical literature to treat
      isolated posterior glottic stenosis is also presented.

PMID- 7503382
TI  - Primary lipogranuloma of the forehead.

PMID- 7503384
TI  - Inter- and intrahemispheric phase changes of diffuse 3 Hz spike-and-wave complex.
AB  - The inter- and intrahemispheric phase characteristics were investigated on
      diffuse 3 Hz spike-and-wave complex (D3SW) in eight epileptic patients who were
      diagnosed with typical absence. The phase of D3SW was analyzed sequentially using
      cross-power spectral arrays dividing D3SW into two components (spike-and-wave
      complex, spike component). The phase of spike-and-wave complex preceded most at
      the midline structure, and delayed symmetrically toward the lateral side of each
      hemisphere in all cases, while not in all cases when spike component was
      investigated. In spite of this symmetry, there was sparse correlation in phase
      change between the homologous hemispheres. There was almost no linear correlation
      between the phase of spike-and-wave complex and the corresponding spike
      component. The author concludes that the 'centrencephalic system' hypothesis
      still plays an important role for the generation of D3SW, and suggest a mechanism
      other than the cortical recurrent inhibition for the generation of wave
      component.

PMID- 7503383
TI  - CNS Young Investigator Award Lecture: molecular analysis of the neurofibromatosis
      2 tumor suppressor.
AB  - Neurofibromatosis 2 (NF2), also known as bilateral acoustic neurofibromatosis or
      central neurofibromatosis, is a severe autosomal dominant disease characterized
      by the development of multiple nervous system tumors. The tumors of NF2, which
      include schwannomas, meningiomas and ependymomas, are histologically benign;
      however, their location and multiplicity led to great morbidity and mortality.
      These tumors commonly affect the general population in their isolated form, and
      have been found to undergo loss of chromosome 22 material in many studies;
      because of this the NF2 gene has been postulated to be a classic tumor
      suppressor. The NF2 gene has recently been isolated and found to encode a new
      member of the protein 4.1 family of cytoskeletal associated proteins which we
      have named merlin. To define the molecular basis of NF2 in germline and tumor
      specimens, we have used single-stranded conformation polymorphism (SSCP) analysis
      to scan the exons of the NF2 gene. We have located and characterized underlying
      causative mutation in 21 of 33 unrelated affected individuals studied, and 32 of
      38 schwannomas. DNA sequence analysis revealed that over 90% of NF2 mutations are
      predicted to lead to a truncated protein due to frameshift, creation of a stop
      codon, or interference with normal RNA splicing. Current studies focus on
      relating the highly variable NF2 phenotype to its genotype, defining alternative
      NF2 related phenotypes, and elucidating the parental origin of new mutation in
      this disease.

PMID- 7503385
TI  - Open label trial with vigabatrin in children with intractable epilepsy.
AB  - Thirty children (20 males, 10 females) with intractable epilepsy received
      vigabatrin (VGB) as an open label basis to preexisting antiepileptic drugs. The
      seizure types consisted of generalized tonic clonic seizure [10], complex partial
      seizure [8], myoclonic seizure [7], and mixed type with simple partial seizure,
      complex partial seizure and/or generalized seizure [5]. The cause of the epilepsy
      was cryptogenic in 16 and symptomatic in 12. The current dosage regime of
      anticonvulsants were maintained during the trial period. VGB at 40-80 mg/kg/day
      were titrated according to the clinical response for a period of 2-24 months. The
      result of treatment was categorized as 'responders' with 13 (43%) having 50-75%
      reduction of seizure frequency; and 'non-responders' which consisted of 17
      children. There was no relationship between outcome of VBG add-on therapy and the
      sex, age of onset, type of seizure, type of epileptic syndrome, etiology,
      associated neurological abnormality, mental retardation or abnormal brain CT/MRI
      findings.

PMID- 7503386
TI  - Posture in low-risk pre-term infants of 30 weeks postmenstrual age.
AB  - In this study we analysed the spontaneous postural behaviour of seven pre-term
      infants of 30 weeks postmenstrual age (PMA). Each infant was observed for a 3-h
      observation period and each minute a sketch of the resting-posture was made.
      Analysis of the postures included the complete observed posture, the distribution
      of adduction and abduction of the hips and shoulders and the distribution of
      extension and flexion of the elbows and knees. Although each infant showed a
      preference posture, no preference posture for the total group could be
      determined. A separate analysis of the positions of the limbs showed a preference
      for fully flexed arms and partly extended legs. Because no group preference
      posture at 30 weeks PMA (nor at other PMA in different studies) could be
      determined, it is suggested that the use of posture as a characteristic of PMA is
      no longer warranted.

PMID- 7503387
TI  - Intracellular alkalosis during hypoxia in newborn mouse brain in the presence of
      systemic acidosis: a phosphorus magnetic resonance spectroscopic study.
AB  - We investigated the in vivo changes in cerebral energy metabolism and pHi in
      newborn mice noninvasively during 8 h of hypoxia with FiO2 = 5%, using phosphorus
      magnetic resonance spectroscopy continuously. The intracellular brain pH (pHi)
      increased from 7.20 +/- 0.03 to 7.36 +/- 0.03 (P < 0.05) at 1 h of hypoxia and
      then decreased gradually. On the other hand, the mixed arterial and venous blood
      pH decreased gradually during hypoxia, reaching a minimum value of 7.16 +/- 0.01
      at the end of the hypoxia. There was no significant difference in PCO2 between
      control (47.4 +/- 0.8 mm Hg) and 1-h hypoxic (49.0 +/- 1.1 mm Hg) mice. The blood
      glucose concentration was significantly increased at 1 h of hypoxia. These
      results indicate that the alkaline shift in pHi during hypoxia was caused neither
      by systemic alkalosis due to hypocapnia nor hypoglycemia.

PMID- 7503388
TI  - The effect of acetazolamide and carbon dioxide on cerebral hemodynamic changes on
      near-infrared spectroscopy in young rabbits.
AB  - The changes of cerebral blood oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and
      total hemoglobin (tHb) induced by acetazolamide and CO2 loading on near-infrared
      spectroscopy (NIRS) were recorded. In anesthetized 2-week-old rabbits,
      acetazolamide (10 mg/kg i.v.) increased HbO2 and tHb, concomitant with an
      increase in tissue PCO2, and decreased HbR only at 5 and 10 min. CO2 loading
      significantly increased HbR and decreased HbO2, and after the termination of CO2
      loading, tHb and HbO2 significantly increased and HbR decreased to nearly the
      baseline value. Thus, NIRS demonstrated cerebral hemodynamic responses as a
      function of vasomotor reactivity to acetazolamide as well as CO2 loading.

PMID- 7503389
TI  - Effects of neonatal hypoxia on brainstem cholinergic neurons-pedunculopontine
      nucleus and laterodorsal tegmental nucleus.
AB  - Hypoxic changes in the cholinergic neurons of the pedunculopontine nucleus (PPN)
      and the laterodorsal tegmental nucleus (LDT) were studied morphologically using
      immunohistochemistry for choline acetyltransferase (ChAT). Fifty-three postnatal
      day (PND) 7 Sprague-Dawley rats were subjected to a hypoxic load of 8% oxygen for
      5 h. The rats which survived were later sacrificed at PND 14 or 28 for
      histological analysis. The results were compared with those obtained from control
      rats. Three weeks after hypoxic load, a decrease in the number of ChAT
      immunoreactive cells, especially in the caudal PPN, was found, although no
      remarkable changes were detected in cell morphology. Since several studies
      support the possibility that the cholinergic system from PPN/LDT is responsible
      for both REM generation and the general motor inhibition during REM sleep, our
      results may account, in part, for the clinical features of hypoxic brain damage
      such as sleep disorders and abnormal muscle tonus.

PMID- 7503390
TI  - Congenital muscular dystrophy with eye and brain involvement. The Turkish
      experience in two cases.
AB  - Eye and brain involvement in congenital muscular dystrophies (CMD) constitute a
      distinct group with a spectrum of brain malformations. We report two such CMD
      patients among our series of 58 cases with CMD. Despite known clinical and
      neuroradiological overlap, we tend to classify them into specific syndromes,
      though this may not be accurate. Molecular genetic studies hopefully will be the
      answer. Our cases are the continuum of increasingly reported CMD cases with
      severe brain manifestations, which come from the area geographically far away
      from those of original descriptions.

PMID- 7503391
TI  - An atypical French form of pyruvate carboxylase deficiency.
AB  - A further case of pyruvate carboxylase deficiency, French type, with a particular
      clinical presentation and evolution is described. The initial neonatal symptoms
      started with respiratory distress, severe metabolic acidosis and a tendency to
      hypoglycemia. However, the clinical course was not rapidly deteriorating. At the
      age of 6 months he presented acute neurological symptoms, respiratory difficulty,
      lactic acidosis and hyperammonemia. Amino and organic acid abnormalities strongly
      suggested pyruvate carboxylase deficiency, which was confirmed by enzymatic
      studies in cultured fibroblasts and liver necropsy. Progressive deterioration and
      bronchopneumonia with cardiac failure and renal insufficiency led to death.
      Anatomic-pathologic studies revealed periventricular cysts and diffuse
      hypomyelination. Prenatal diagnosis of a further sibling was performed. The
      neonatal clinical presentation, biochemical abnormalities, and the presence of
      periventricular cysts suggested a French phenotype. However, the clinical course
      was less severe, suggesting a residual enzymatic activity and a possible milder
      mutation.

PMID- 7503392
TI  - A sporadic case of very slow progressive leukodystrophy involving the cerebellar
      peduncles.
AB  - We describe a patient with infantile onset leukodystrophy involving the
      cerebellar peduncles. She had mild mental retardation, spastic diplegia and mild
      cerebellar ataxia. The peripheral nerves seemed to be normal. The characteristic
      MRI findings in this case were extensive lesions of the white matter involving
      the cerebellar peduncles. In addition there was ventricular enlargement with a
      markedly decreased volume of the white matter and a hypoplastic corpus callosum.
      The clinical and laboratory findings imply that the white matter lesions in this
      patient were the result of delayed myelination rather than demyelination. The
      patient was evaluated for known metabolic and degenerative diseases, but no
      abnormalities were observed. Her symptoms and neuroimaging findings did not fit
      the criteria for any defined leukodystrophy.

PMID- 7503393
TI  - Aicardi syndrome with multiple tumors: a case report with literature review.
AB  - A 5-year-old girl with Aicardi syndrome, choroid plexus papilloma and multiple
      gastric hyperplastic polyps is reported. Gastric polyposis is unusual in the
      pediatric age group and has not previously been reported in a patient with
      Aicardi syndrome. A variety of uncommon benign and malignant tumors have been
      associated with Aicardi syndrome; this literature is briefly reviewed. The
      increased frequency of tumors in Aicardi syndrome should be kept in mind when
      evaluating these patients.

PMID- 7503394
TI  - Myopathic involvement in two cases of Hallervorden-Spatz disease.
AB  - Muscle biopsy was performed in two patients with Hallervorden-Spatz disease and
      increased serum creatine kinase levels. Morphological analysis showed myopathic
      signs such as subsarcolemmal accumulation of myeloid structures, dense bodies and
      debris, endomysial macrophage activation, focal necrosis and fiber splitting. We
      emphasize the finding of muscle involvement in Hallervorden-Spatz disease, like
      in other forms of neuroacanthocytosis.

PMID- 7503396
TI  - Outcome of facial nerve palsy in 24 children.
AB  - Of 24 children with facial palsy, 6 (25%) had recurrent attacks. Complete
      recovery occurred in 21 (88%). Electrophysiological tests including direct
      stimulation of the facial nerve and blink reflex were performed in 12 serially to
      compare the prognostic value. Only direct response had prognostic significance in
      predicting the outcome. A normal direct response predicts a better prognosis (P =
      0.002) whereas abnormal blink reflex can be associated with complete or
      incomplete recovery.

PMID- 7503395
TI  - Reduction of seizure frequency with clomipramine in patients with complex partial
      seizures.
AB  - Two patients with complex partial seizures who had been refractory to various
      antiepileptics were treated with clomipramine. The frequency of the seizures was
      reduced to 0-30% of the original levels. It has been reported that imipramine is
      effective in absence and minor motor seizures, and its antiepileptic effect is
      thought to be related to the inhibition of the presynaptic re-uptake of serotonin
      and norepinephrine. The basic effect of clomipramine is the same as that of
      imipramine except that the inhibitory action of clomipramine on serotonin re
      uptake is 5- to 10-times more potent than that of imipramine. It is implied that
      clomipramine may be of use in the treatment of partial epilepsies.

PMID- 7503397
TI  - Leukotrienes as therapeutic target in asthma.

PMID- 7503398
TI  - Adverse reactions to food. European Academy of Allergology and Clinical
      Immunology Subcommittee.

PMID- 7503399
TI  - Specific serum IgE in the diagnosis of egg and milk allergy in adults.
AB  - Levels of specific serum IgE to cow's milk, whole hen's egg, egg white, and egg
      yolk were compared to the outcome of double-blind, placebo-controlled food
      challenge (DBPCFC) with fresh egg and/or milk in 21 adults with a case history of
      immediate hypersensitivity to egg and/or milk. Specific serum IgE was measured by
      four different commercially available tests and by an inhouse Maxisorp RAST using
      freshly prepared food extracts. Sensitivities and negative predictive accuracies
      were generally high with egg white and milk, but low with egg yolk. Specificities
      and positive predictive accuracies were low for all allergens and tests. Changing
      the cutoff levels did not improve the ability of the tests to predict clinical
      allergy. Among commercially available test allergens, egg white gave the most
      consistent results in levels and class scores, and the highest degree of
      concordance with DBPCFC, whereas egg yolk and milk varied more. Applying freshly
      prepared food extracts in Maxisorp RAST did not improve diagnostic value.
      Measuring specific serum IgE levels in control subjects tolerant to egg/milk
      showed that false positive reactions occurred frequently among patients with
      another food allergy and atopic dermatitis, whereas most tests were likely to be
      negative in pollen-allergic and nonallergic volunteers. In conclusion, specific
      IgE measurements with egg white and milk were useful for exclusion of symptomatic
      hypersensitivity to egg and milk in patients with a positive history, whereas
      DBPCFC is still mandatory in patients with positive history and positive test.
      Measuring egg-yolk-specific IgE or using freshly prepared food extracts for
      specific IgE measurements added no further diagnostic information. The rate of
      clinically insignificant positive test results seems to be influenced by the
      prevalence of other food allergies and/or atopic dermatitis in the population
      under study.

PMID- 7503400
TI  - Allergen cross-reactivity between Pityrosporum orbiculare and Candida albicans.
AB  - Pityrosporum orbiculare and Candida albicans extracts were separated by SDS-PAGE,
      and IgE binding was detected by immunoblotting with 21 patient sera that were
      RAST positive to both yeasts. Cross-wise inhibition was performed of IgE binding
      of a serum pool containing IgE antibodies to both yeasts. The pool was mixed with
      serial dilutions of P. orbiculare or C. albicans extracts, and incubated with
      strips containing separated allergen. IgE binding was quantified by densitometric
      scanning and percent inhibition was calculated as well as the respective ratios
      between required extract concentration for 50% inhibition in heterologous
      compared to homologous inhibition for each component (inhibition ratio). Ten
      components of P. orbiculare were detected by more than 60% of the sera. IgE
      binding to C. albicans was weak, and only to four bands was IgE binding detected
      by more than 30% of the sera. The most important C. albicans allergen was a 48
      kDa band, to which IgE of half of the patient sera bound. There was little
      inhibition of IgE binding to P. orbiculare with C. albicans. Thus, all but three
      components exhibited an inhibition ratio higher than 100. The inhibition ratio of
      the 48-kDa C. albicans compound was 50, thus indicating some degree of cross
      reactivity. Significant cross-reactivity was shown by C. albicans compounds of
      18, 24, 26, 34, and 38 kDa, the inhibition ratios of which were less than 10.
      There was some degree of cross-reactivity between apparent protein allergens of
      the two yeasts, but IgE antibodies to C. albicans do not merely reflect
      sensitization to P. orbiculare.

PMID- 7503401
TI  - Inhaled formoterol dry powder in the treatment of patients with reversible
      obstructive airway disease. A 3-month, placebo-controlled comparison of the
      efficacy and safety of formoterol and salbutamol, followed by a 12-month trial
      with formoterol.
AB  - Inhaled formoterol is a potent selective beta 2-agonist with rapid onset and at
      least 12-h duration of bronchodilation. The aim of the study was to compare the
      bronchodilating effect of inhaled formoterol dry powder (dp) 12 micrograms b.i.d.
      with salbutamol dp 400 micrograms q.i.d. and placebo in patients with reversible
      obstructive airway disease (ROAD). The study design consisted of a closed 12-week
      double-blind, placebo-controlled, multicenter trial followed by an open
      noncomparative, multicenter, 12-month follow-up trial, in which the tolerability
      of formoterol dp was assessed. A total of 304 patients (146 men, 158 women) aged
      18-79 years, ill during 0.1-64 years, were randomized. No demographic or baseline
      differences were found among the different treatment groups. The bronchodilating
      effect of formoterol, assessed by morning premedication PEFR, was significantly
      superior to placebo (P < 0.0001) and salbutamol (P < 0.0001). Efficacy was
      maintained during the open follow-up study with 12 micrograms b.i.d. in most of
      the patients. A few patients, however, needed 24 micrograms b.i.d. to control
      their ROAD. Formoterol 12 micrograms b.i.d. significantly reduced morning and
      evening asthma symptoms and sleep disturbances, and reduced significantly the
      need for rescue medication. The tolerability of the three treatment groups was
      comparable. In conclusion, formoterol 12 micrograms dp b.i.d. was significantly
      superior to both salbutamol 400 micrograms dp q.i.d. and placebo, and reduced
      asthma symptoms significantly. Overall, formoterol showed a tolerability profile
      comparable to that of salbutamol, and no tachyphylaxis was observed during 1 year
      of treatment.

PMID- 7503402
TI  - Role of two-dimensional electrophoretic analysis in the diagnosis and
      characterization of IgD monoclonal gammopathy.
AB  - Over a period of 5 years, an isolated light chain (kappa = 9, lambda = 12) was
      detected in 21 sera by immunofixation electrophoresis. Further analysis with anti
      delta- and anti-epsilon-specific antisera identified four delta heavy chains, all
      associated with a lambda light chain, and no epsilon heavy chains. For evaluation
      of the role of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in
      the diagnosis of IgD paraproteins, as a possible alternative or complement to
      immunofixation, IgD paraproteins were retrospectively analyzed by 2D-PAGE. Delta
      Heavy chains migrated to gel areas clearly distinguishable from other heavy
      chains alpha, gamma, or mu, and in a wide range of isoelectric points (pI: 5.4
      8). In one serum, the monoclonal delta chain had a pI range comparable to that of
      albumin and was undetectable. However, all four delta chains were easily
      identified when analyzed from affinity-purified immunoglobulin fractions. These
      observations showed the following: 1) IgD paraproteins are not rare among
      apparently isolated monoclonal light chains detected by routine immunofixation,
      strongly confirming the need for further analysis with anti-delta antisera,
      before assumption of a light-chain disease. 2) 2D-PAGE analysis of affinity
      purified immunoglobulin fractions allowed correct identification of IgD
      monoclonal gammopathies in all cases. 3) However, although 2D-PAGE analysis is
      now easy to perform, well standardized, and highly sensitive, this technique
      remains time-consuming and expensive, and does not appear suitable for routine
      practice as a first-line diagnostic procedure. 2D-PAGE should find its place as a
      complement to immunofixation and in the definitive demonstration, in selected
      ambiguous cases, of the clonal pattern of a suspected gammopathy at
      immunofixation.

PMID- 7503403
TI  - Basic aspects related to penicillin-allergy skin testing: on the variability of
      the hapten-paratope interaction.
AB  - Ampicillin and benzylpenicillin conjugated to human serum albumin were used as
      immunogens in order to obtain antihaptenic IgG responses in outbred guinea pigs
      according to different schedules, all involving complete Freund's adjuvant. The
      individual responses were characterized by ELISA and by ELISA inhibition using
      ampicillin, benzylpenicillin, and carbenicillin peptidic conjugates for coating
      and for inhibition. In several instances, drastically reduced cross-reactivity
      and even its absence were observed, although the penicillin antigens differ only
      in the side-chain. The notion that the invariantly present thiazolidine ring will
      always provide significant binding to antibodies against all penicillins
      differing only in the side-chain has to be dropped. The experiments were
      performed in relation to newer findings of clinical penicillin-allergy skin
      testing which suggest that benzylpenicillin-based reagents alone are not able to
      detect or predict all reactions against semisynthetic penicillins. The
      experimental evidence here obtained corroborates this conclusion.

PMID- 7503404
TI  - Costimulation of CD3/TcR complex with either integrin or nonintegrin ligands
      protects CD4+ allergen-specific T-cell clones from programmed cell death.
AB  - An optimal stimulation of CD4+ cells in an immune response requires not only
      signals transduced via the TcR/CD3 complex, but also costimulatory signals
      delivered as a consequence of interactions between T-cell surface-associated
      costimulatory receptors and their counterparts on antigen-presenting cells (APC).
      The intercellular adhesion molecule-1 (ICAM-1, CD54) efficiently costimulates
      proliferation of resting, but not antigen-specific, T cells. In contrast, CD28
      and CD2 support interleukin (IL)-2 synthesis and proliferation of antigen
      specific T cells more efficiently than those of resting T cells. The molecular
      basis for this differential costimulation of T cells is poorly understood.
      Cypress-specific T-cell clones (TCC) were generated from four allergic subjects
      during in vivo seasonal exposure to the allergen. Purified cypress extract was
      produced directly from fresh collected pollen and incubated with the patients'
      mononuclear cells. Repeated allergen stimulation was performed in T-cell cultures
      supplemented with purified extract and autologous APC. The limiting-dilution
      technique was then adopted to generate allergen-specific TCC, which were also
      characterized by their cytokine secretion pattern as Th0 (IL-4 plus interferon
      gamma) or Th2 (IL-4). Costimulation-induced proliferation or apoptosis was
      measured by propidium iodide cytofluorometric assay. By cross-linking cypress
      specific CD4+ and CD8+ T-cell clones with either anti-CD3 or anti-CD2, anti-CD28,
      and anti-CD54 monoclonal antibodies, we demonstrated that CD4+ clones (with Th0-
      or Th2-type cytokine production pattern) undergo programmed cell death only after
      anti-CD3 stimulation, whereas costimulation with either anti-CD54 or anti-CD28
      protects target cells from apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503405
TI  - Effect of terfenadine and budesonide on nasal symptoms, olfaction, and nasal
      airway patency following allergen challenge.
AB  - The study investigated the effect of the oral H1-blocker terfenadine on allergen
      challenge in subjects with nasal allergy in comparison with the topical steroid,
      budesonide. A randomized, placebo-controlled, double-blind, crossover study with
      3 experimental days was performed outside the pollen season. Seventeen nonsmokers
      with hay fever (symptoms, positive skin prick test, and RAST against timothy)
      were treated for 14 days before each experimental day, where the response to
      nasal challenge with four different concentrations of timothy was measured every
      15 min for 6 h. The nasal cavity dimensions were measured by acoustic rhinometry
      and the olfactory function as the threshold for the sense of smell of butanol.
      Nasal symptoms were determined by questionnaires. Both terfenadine and budesonide
      dry powder had an effect on the hay fever symptoms during nasal pollen challenge.
      Terfenadine was more efficient than budesonide against histamine-mediated
      symptoms such as sneezing and itching. Budesonide increased nasal airway
      dimensions better than terfenadine (P < 0.01). A marked effect of budesonide was
      seen 1-2 h after challenge, suggesting an effect on "early late phase" reaction
      in the nose. In 7/17 subjects, a significant (P < 0.05) improvement of olfactory
      function after budesonide treatment was seen. In conclusion, topical steroid
      (budesonide) is superior to antihistamine (terfenadine) in treatment of nasal
      congestion in hay fever, especially for the postchallenge reaction, and may, in
      some cases, relieve the decreased sense of smell during pollen challenge.

PMID- 7503406
TI  - An enzyme-linked immunosorbent assay specific for transient (29-37-kDa) fragments
      of soluble CD23/IgE-binding factors.
AB  - The low-affinity IgE receptor (Fc epsilon RII) of B cells and monocytes--also
      known as CD23--is released from the cell surface by proteolytic cleavage to yield
      a series of soluble fragments which can accumulate in cell culture supernatants
      and body fluids. Of these, the most stable is a 25-kDa molecule which is
      generated from transient intermediates ranging in size from 29 to 37 kDa. It has
      been claimed that these latter species act as IgE-promoting factors while the 25
      kDa molecule is endowed with various cytokine-like activities which are
      independent of IgE binding. We describe here a novel enzyme-linked immunosorbent
      assay (ELISA) which allows for the distinction between these two classes of
      soluble CD23. It is based on the observation that the CD23 antibody EBVCS1 can
      capture recombinant 29-kDa and 37-kDa fragments of CD23 but does not bind to the
      25-kDa species: when EBVCS5 is used as the capture antibody, all three fragments
      are bound. The availability of these differential ELISA should facilitate
      investigations on the biological properties of CD23 fragments in health and
      disease.

PMID- 7503407
TI  - Circulating leukocyte adhesion molecules in stable asthma and nonobstructive
      chronic bronchitis.
AB  - Leukocyte adhesion molecules have been associated with airway inflammatory
      diseases such as asthma and obstructive chronic bronchitis. Lately, it has become
      possible to measure circulating forms of cell adhesion molecules (cCAMs) in body
      fluids. Elevated serum levels have been found in acute asthma and in obstructive
      chronic bronchitis. We investigated whether the patterns of cICAM-1, cVCAM-1, and
      cE-selectin could serve as markers for airway inflammation in stable asthma and
      stable nonobstructive chronic bronchitis. Small-volume bronchial lavage (BL) and
      serum from 15 controls, 13 asthmatics without steroid inhalation therapy, 11
      asthmatics with regular steroid inhalation therapy, and 10 smokers with chronic
      bronchitis were analyzed. We found cICAM-1, cVCAM-1, and cE-selectin to be
      present in serum from patients with stable asthma and stable nonobstructive
      chronic bronchitis. Only cICAM-1 was found in BL fluid. No differences were seen
      between the subject groups for either cCAM, but levels of ECP were increased in
      the non-steroid-treated asthmatic group. Subject atopy or smoking did not
      increase the cCAM levels. In conclusion, the degree of airway inflammation in
      stable nonobstructive chronic bronchitis and stable asthma does not appear to be
      well associated with circulating ICAM-1, cVCAM-1, and cE-selectin.

PMID- 7503408
TI  - Enzymatic method for determination of branched-chain amino acid aminotransferase
      activity.
AB  - A spectrophotometric assay for the determination of branched-chain L-amino acid
      aminotransferase activity is described. It is based on the transamination of L
      leucine in the presence of 2-oxoglutarate yielding 4-methyl-2-oxopentanoate. The
      rate of formation of the branched-chain 2-oxo acid is specifically monitored in a
      coupled enzymatic reaction using NAD(+)-dependent D-2-hydroxyisocaproate
      dehydrogenase from Lactobacillus casei ssp. pseudoplantarum as coupling enzyme by
      measuring the decrease in NADH absorbance at 334 nm. Optimized assay conditions
      are provided as evaluated for the (iso)enzyme from rat heart.

PMID- 7503410
TI  - Long-term chemotaxis studies on adherent cells: effect of platelet-derived growth
      factor-BB on human vascular smooth muscle cell migration.
AB  - Several chemotaxis methods have been developed which allow the study of different
      aspects of cell migration. The major limitation of such methods is the lack of a
      sustained chemotactic signal. Long-term chemotaxis phenomena which are known to
      take place in vivo have remained largely uninvestigated. Ways to maintain
      sustained chemotactic signals were sought and the used to investigate the long
      term chemotactic effect of platelet-derived growth factor BB (PDGF-BB) on human
      vascular smooth muscle cells (HVSMC). PDGF-BB was adsorbed onto microcarrier
      beads and then embedded in agar. PDGF-BB diffusion was slow and a high and
      sustained local concentration was maintained in the agar. When PDGF-BB-loaded
      beads embedded in agar were placed at the edge of a tissue culture dish with
      HVSMC plated in the center, preferential movement was observed in the direction
      of the PDGF-BB source. This method was subsequently used to study directional
      movement of HVSMC arising from explants. This report demonstrates that PDGF-BB if
      present in an anisotropic concentration induces directional cell movement from
      such explants. By allowing the study of the effect of sustained chemotactic
      signals upon cultured cells or cells arising from explants, this method may
      provide a suitable model for investigating in vivo chemotaxis phenomena.

PMID- 7503411
TI  - Positional isomerization of trans-3-hexadecenoic acid employing 2-amino-2-methyl
      propanol as a derivatizing agent for ethylenic bond location by gas
      chromatography/mass spectrometry.
AB  - The effect of derivatization with 2-amino-2-methyl-propanol on trans-3
      hexadecenoic acid was investigated as part of the identification of the trans-3
      hexadecenoic acid in two Nova Scotian seaweeds. After the extraction of the total
      fatty acids and their methylation, the monoenoic trans fraction was isolated by
      thin-layer chromatography on silica gels impregnated with silver nitrate. This
      fraction was first analyzed by gas chromatography and showed the presence of the
      trans-3-hexadecenoic acid; other fatty acids were not present. The isolated
      fraction was derivatized with 2-amino-2-methyl-propanol prior to analysis by gas
      chromatography/mass spectrometry. The chromatogram obtained showed the presence
      of a positional isomer formed during the derivatization of the trans-3
      hexadecenoic acid. The mass spectrum showed a prominent [M+H] and diagnostic ions
      for the identification of the unknown isomer, corresponding to the 4,4
      dimethyloxazoline (DMOX) derivative of a presumed 2-hexadecenoic acid. Definitive
      confirmation of the ethylenic bond position was obtained by oxidative ozonolysis
      of the DMOX derivatives of the fatty acids under investigation. Infrared
      spectroscopy showed that the artifact formed during the DMOX derivatization of
      trans-3-hexadecenoic acid was the DMOX derivative of cis-2-hexadecenoic acid.

PMID- 7503409
TI  - Analysis of polymerase chain reaction-amplified DNA products by mass spectrometry
      using matrix-assisted laser desorption and electrospray: current status.
AB  - Recent advances in molecular biology are making it possible to diagnose genetic
      diseases and identify pathogens through the analysis of DNA. As clinical
      applications for molecular diagnosis increase, rapid, reliable methods for
      determination of DNA size will be needed. Mass spectrometry offers the potential
      of analyzing amplified DNA quickly and reliably, without the need for gel-based
      separation and sample labeling steps that are conventionally employed. Both
      electrospray ionization and matrix-assisted laser desorption/ionization have been
      evaluated for the size analysis of DNA using both synthetic oligonucleotides and
      PCR-amplified samples corresponding to bases 1626 to 1701 of the cystic fibrosis
      transmembrane conductance regulator gene. Both technologies have been
      demonstrated to have mass range and sensitivity required for the analysis of PCR
      amplified DNA in this size range using minimal sample preparation. Steps required
      to incorporate either ionization technique into a reliable analytical scheme for
      the rapid, routine analysis of DNA are outlined.

PMID- 7503412
TI  - Nonselective and efficient fluorescent labeling of glycans using 2-amino
      benzamide and anthranilic acid.
AB  - Reaction conditions for conjugation of two fluorescent ortho-substituted aniline
      derivatives, 2-amino benzamide (2-AB) and 2-anthranilic acid (2-AA), to N- and O
      glycans have been investigated. Conjugation conditions for attaching 2-AB and 2
      AA to core-fucosylated and non-fucosylated glycans were developed using complex N
      glycans radiolabeled at the nonreducing terminus with [3H]C6-galactose. Optimal
      conditions for each of the following reaction parameters were experimentally
      defined: [glycans], [2-AB] or [2-AA], solvent and acid composition, temperature
      and time of Schiff's base formation, nature of reductant, and temperature and
      time of reduction. Using the optimized reaction conditions it has been shown with
      several standard glycans and glycoprotein-derived glycan libraries that (i) molar
      labeling efficiencies are high and essentially independent of the amount of
      glycans; (ii) negligible (< 2 mol%) desialylation occurs during conjugation;
      (iii) glycan labeling is nonselective, i.e., independent of glycan structure; and
      (iv) insignificant fluorescent or chemical "blank" is recovered during the glycan
      labeling and purification protocol. Labeling glycan pools with 2-AB or 2-AA
      therefore allows representative glycan profiles to be obtained and also allows
      relative molar quantitation of individual glycans in a pool. The 2-AB label is
      compatible with several chromatographic means for separation of carbohydrates
      including Bio Gel P4 gel permeation, high-performance anion-exchange
      chromatography with fluorescence detection, and a variety of HPLC procedures, as
      well as with mass spectrometric methods including matrix-assisted laser
      desorption-mass spectrometry and electrospray-mass spectrometry. The 2-AA label
      is particularly well-suited for electrophoretic separations by polyacrylamide gel
      electrophoresis. These fluorophores show high intrinsic sensitivity and thus
      facilitate very sensitive analysis of protein glycosylation.

PMID- 7503413
TI  - Molecular study of P-glycoprotein in multidrug resistance using surface plasmon
      resonance.
AB  - P-Glycoprotein is an integral membrane protein which mediates the energy
      dependent efflux of various antitumor agents from multidrug-resistant cancer
      cells. Surface plasmon resonance was used for the detection of P-glycoprotein
      after solubilization from drug-resistant and drug-sensitive Chinese hamster ovary
      cells and for the analysis of its interaction with cyclosporin A, a competitive
      inhibitor of drug efflux. Detection of P-glycoprotein relied on its binding to
      the monoclonal antibody C219 which was immobilized on a sensor chip. Binding of
      Zwittergent 3-14-solubilized P-glycoprotein to the antibody was concentration
      dependent and reflected the relative abundance of P-glycoprotein in both cell
      lines. It was abolished when C219 was omitted or replaced by a rabbit anti-mouse
      IgG antibody and considerably reduced after precipitation of P-glycoprotein with
      wheat germ agglutinin. Preincubation of solubilized proteins with cyclosporin A
      increased the amount of protein bound to the antibody by approximately 30%. These
      results indicate that surface plasmon resonance is well suited to the detection
      of P-glycoprotein from biological samples and shows promise as a tool for the
      study of its interaction with different drugs.

PMID- 7503414
TI  - Detection of dopachrome isomerase on gels and membranes.
AB  - Dopachrome isomerase, which mediates the conversion of dopachrome to
      dihydroxyindoles, is an enzyme affiliated with the melanogenic pathway found in
      most vertebrates and invertebrates. We have recently reported an activity
      staining procedure for detecting this enzyme after electrophoresis on tyrosinease
      embedded polyacrylamide gels using dopa [K. Nellaiappan, G. Nicklas, and M.
      Sugumaran, (1994) Anal. Biochem. 220, 122-128]. The usefulness of this method is
      limited to the availability of good quality of tyrosinase. To overcome the
      limitations of nonavailability as well as batch to batch variation in the
      specific activity of commercially available tyrosinase which will affect the
      staining, we have developed a new stain technique using chemically made
      dopachrome for the detection of dopachrome isomerase. The new method employs the
      use of dopachrome generated in situ by the oxidation of dopa with periodate.
      Dopachrome isomerase initially appears as a bluish-purple (melanochrome) band
      against an orange-red background. Eventual transformation of melanochrome to dark
      insoluble melanin polymer produces a black band corresponding to dopachrome
      isomerase activity. Continuous washing of the gel clears the background.
      Usefulness of this technique to stain dopachrome isomerase (a) in different
      organisms and (b) on polyacrylamide gels, agarose gels, and nitrocellulose
      membranes is demonstrated. In addition, conditions to stain the enzyme on
      nitrocellulose membranes using mushroom tyrosinase are described. Comparison of
      the effectiveness of tyrosinase versus periodate staining procedure reveals that
      the former method is superior to the latter in detecting dopachrome isomerase.
      The periodate method overcomes the problems associated with the quality of
      commercially available tyrosinase and its nonavailability in certain regions.

PMID- 7503415
TI  - Quantitative determination of polyethylene glycol based upon its salting out and
      partitioning of a dye into the resulting aqueous two-phase system.
AB  - A method is described that allows quantitative determination of polyethylene
      glycol (PEG) concentrations by spectrophotometric measurement of fluorescein dye
      absorbance after its partitioning into an aqueous two-phase system containing
      mPEG (M(r) 5 kDa) in the upper phase and ammonium sulfate in the lower phase. The
      absorbance decrease of fluorescein in the lower phase is directly proportional to
      the mPEG concentration, with two proportionality constants equal to 4.42 x 10(5)
      and 2.84 x 10(5) M-1 cm-1 in the range of 0-0.4 and 0.4-1 microM, respectively.
      This experimental technique can be extended to PEGs of other molecular weights by
      means of calibration curves that give for each size of PEG the adequate
      proportionality constants. The results indicate that the quantitative
      determination is not affected by the presence of many substances such as
      proteins, reducing agents, and salts, at the usual concentrations.

PMID- 7503416
TI  - Crystal violet as an indicator dye for nonequilibrium pH gradient electrophoresis
      (NEpHGE).
AB  - I found that a blue-colored dye, crystal violet, is a useful indicator for
      nonequilibrium pH gradient electrophoresis (NEpHGE). Unlike isoelectrofocusing,
      NEpHGE basically depends on the nonequilibrium gradient; therefore, the location
      of the proteins differs with acrylamide concentration or voltage used. To get
      reproducible results, colored marker which indicates the end of the
      electrophoresis might be very helpful. Crystal violet is an adequate dye for this
      purpose. This deeply colored, nontoxic material has a positive charge and
      migrated slightly faster than almost all proteins on NEpHGE. This dye affected
      neither the formation of pH gradient nor migration of proteins. Moreover, the
      ratio of migration (protein/dye) in the NEpHGE gels did not change under
      different conditions tested. Therefore, the addition of trace amounts of this dye
      gives a convenient endogenous color indicator to determine the end of the NEpHGE.
      Other positively charged dyes could be used as such an indicator, but some dyes
      (for example, methylene blue) lost their color by reduction during
      electrophoresis. Some dyes (for example, ethidium bromide) migrate too fast;
      therefore, they were not suitable indicators for NEpHGE.

PMID- 7503417
TI  - Real-time fluorescence detection of RNA amplified by Q beta replicase.
AB  - Amplification of RNA probes by Q beta replicase can be used to detect a wide
      range of analytes with a potential sensitivity of a single molecule. A system has
      been developed in which Q beta amplification of midivariant-(MDV)-based RNA is
      measured in real time by fluorescence. This was accomplished by including a
      fluorescent intercalating dye, propidium iodide, in the reactions and monitoring
      the fluorescence change using a custom fluorometer. The time at which
      fluorescence is detectable above background is referred to as the "response time"
      and is calculated using curve-fitting algorithms. A response time is inversely
      and linearly proportional to the logarithm of the number of template RNA
      molecules which initiated the reaction. Therefore, this system permits an unknown
      amount of input RNA probe to be quantified through 11 orders of magnitude when
      compared to a standard curve. Under the described conditions with MDV RNA, the
      response time occurs when about 3 x 10(11) RNA molecules are synthesized and
      occurs within the exponential phase of the reaction, before the number of active
      enzyme molecules are saturated with RNA templates. This system has been used to
      determine the replication properties of MDV RNA reporter molecules bearing
      specific probe sequences and to develop hybridization assays for the clinical
      diagnostic field.

PMID- 7503418
TI  - Analysis of mono- and oligosaccharide isomers derivatized with 9-aminopyrene
      1,4,6-trisulfonate by capillary electrophoresis with laser-induced fluorescence.
AB  - A method of analysis of isomers of mono- and oligosaccharides derivatized with 9
      aminopyrene-1,4,6-trisulfonate (APTS) by capillary electrophoresis (CE) in simple
      buffer systems is presented. The derivatization chemistry is performed at 75
      degrees C for 1 h for most mono- and oligosaccharides. Sialyllactose was
      derivatized at 37 degrees C for 15 h without significant desialylation. Most of
      the APTS derivatized isomers of mono- and oligosaccharides are resolved in
      buffers such as acetate (pH 5.0), 3-(N-morpholino)-propanesulfonic acid (pH 7.0),
      and phosphate (pH 7.4). The mechanism of CE separation using the above buffers is
      based on the differences in hydrodynamic volume of the derivatized species and is
      different from that in borate or high pH buffer.

PMID- 7503419
TI  - Effect of separation conditions on automated isoelectric focusing of carbohydrate
      deficient transferrin and other human isotransferrins using the PhastSystem.
AB  - To investigate the effect of automated isoelectric focusing conditions in the
      PhastSystem, e.g., the point of sample application, prerun and separation times,
      and minimized gels on isotransferrin band pattern, human sera were analyzed with
      native transferrin iron load, after iron saturation or iron depletion in vitro.
      Varying the focusing conditions we found (i) Point of sample application (anode,
      middle of the gel, cathode) strongly affected transferrin iron loss. It was
      greatest at the anode and least at the cathode. (ii) Without prerun, distinct
      transferrin iron loss also occurred. A short prerun time prevented iron loss, but
      increasing it did not improve transferrin iron load stability as stated by
      others. (iii) An inappropriately long separation time inevitably yielded iron
      loss. In conclusion, inappropriate isoelectric focusing conditions strongly
      affect iron load stability of isotransferrins (obviously via low pH within the
      gel), resulting in transferrin iron release and cofocusing of isotransferrins
      with different sialic acid or iron contents. For determination of carbohydrate
      deficient transferrin, such conditions resulted in overestimation of the marker
      of chronic alcohol abuse. Our findings may be of guiding importance for
      isoelectric focusing of protein-ligand complexes. We recommend the procedure
      described for development of isoelectric focusing of protein-ligand complexes.

PMID- 7503420
TI  - Halophilic protein stabilization by the mild solubilizing agents nondetergent
      sulfobetaines.
AB  - In this work, experiments performed on pig heart and halophilic malate
      dehydrogenase as well as halophilic elongation factor Tu demonstrate a protein
      stabilization property from the recently described mild solubilizing agents
      nondetergent sulfobetaines. A practical application is given by the separation of
      halophilic bacteria elongation factor Tu and halophilic malate dehydrogenase by
      high-performance ion-exchange chromatography achieved at reduced salt levels
      without significant loss of activity.

PMID- 7503421
TI  - Biosynthetic preparation of isotopically labeled heme.
AB  - An efficient method for the preparation of isotopically enriched heme has been
      developed. This method utilizes a commercially available bacterial host and
      plasmid, into which a synthetic gene encoding for rat liver outer mitochondrial
      membrane cytochrome b5, a heme-binding protein, has been inserted. The method
      described in this report utilizes the efficient synthesis of the cytochrome b5
      polypeptide together with the enhanced biosynthesis of heme brought about by
      addition of the first committed precursor in heme biosynthesis, delta
      aminolevulinic acid. Apocytochrome b5 sequesters heme as the macrocycle is being
      synthesized in order to form holocytochrome b5, thus avoiding toxic
      concentrations of free macrocycle in the cell. Relatively high concentrations of
      free heme in the cell have been shown to stimulate excretion of heme precursors
      such as coproporphyrinogen and uroporphyrinogen (W. F. Harris III, R. S.
      Burkhalter, W. Lin and R. Timkovich, (1993) Bioorg. Chem. 21, 209-220), therefore
      causing isotopic dilution of the labeled material. The heme obtained using this
      methodology was determined to be > 85% enriched. Because the heme in cytochrome
      b5 is not covalently attached to the polypeptide, it can be extracted and used in
      other applications. Use of glutamate, a precursor of delta-amino-levulinate
      biosynthesis in Escherichia coli, did not result in high levels of isotopic
      incorporation into heme, thus pointing out to the importance of using a labeled
      precursor that is committed to heme biosynthesis in order to obtain high levels
      of isotopic labeling.

PMID- 7503422
TI  - Continuous spectrophotometric assay of human lysosomal cathepsin A/protective
      protein in normal and galactosialidosis cells.
AB  - We describe a method to determine the substrate specificity of human lysosomal
      carboxypeptidase, cathepsin A/protective protein, using furylacryloyl (FA)-Phe-X
      dipeptides as substrates. These dipeptides contain a chromophore which allows
      continuous spectrophotometric assay at wavelengths above 324 nm with little
      interference from protein absorbance. The results obtained with cathepsin A
      purified from human placenta demonstrate that the enzyme has the highest affinity
      for substrates with large hydrophobic (Phe, Leu) or positively charged (Arg)
      amino acid residues in P1' position. The three substrates (FA-Phe-Phe, FA-Phe
      Leu, and FA-Phe-Ala) which demonstrated the highest specificity (kcat/Km) for the
      purified enzyme were then used to assay cathepsin A activity in cultured skin
      fibroblasts from patients affected with galactosialidosis, an inherited lysosomal
      storage disease caused by the genetic deficiency of cathepsin A. Residual
      cathepsin A activity in galactosialidosis fibroblasts was lower than 6% of
      controls, indicating the high specificity of the assay method.

PMID- 7503423
TI  - Purification of functionally sealed cytoplasmic side-out plasma membrane vesicles
      from Saccharomyces cerevisiae.
AB  - Highly purified plasma membrane vesicles were prepared from yeast protoplasts by
      a combination of osmotic lysis, differential centrifugation, and separation in an
      aqueous dextran/polyethylene glycol two-phase system. The vesicles were
      predominantly (85-90%) of cytoplasmic side-out orientation and displayed large
      ATP-dependent proton pumping activity which was inhibited by vanadate (100
      microM) but not by bafilomycin or nitrate. The preparation presented a distinct
      polypeptide profile with respect to the total membrane fraction and was enriched
      in the 110-kDa polypeptide corresponding to the plasma membrane H(+)-ATPase. This
      preparation of native plasma membranes vesicles is especially suitable for
      functional studies in vitro.

PMID- 7503424
TI  - Quantitative measurement of sphingosine 1-phosphate in biological samples by
      acylation with radioactive acetic anhydride.
AB  - We describe here in detail the development of a method to quantitatively measure
      sphingosine 1-phosphate (Sph-1-P), a bioactive sphingolipid. Sph-1-P was first
      extracted from cells into the upper aqueous phase under alkaline conditions by
      Folch's phase separation and then reextracted into the lower chloroform phase
      under acidic conditions. This phosphorylated sphingoid base extracted was
      quantitatively converted to N-[3H]-acetylated Sph-1-P, that is [3H]C2-ceramide 1
      phosphate (C2-Cer-1-P), by N-acylation with [3H]acetic anhydride. The [3H]C2-Cer
      1-P formed with the acylation was resolved by thin-layer chromatography, detected
      with autoradiography, and quantitated by scraping the corresponding band and
      counting its radioactivity with a scintillation counter. This assay allows
      quantification of Sph-1-P over a range from at least 100 pmol (often 30 pmol) to
      10 nmol (the highest level tested). The utility and validity of our assay were
      demonstrated using human platelets. The amount of Sph-1-P in platelet extracts
      was proportional to the cell number and calculated as 141 +/- 4 pmol/10(8) cells
      (mean +/- SD, n = 3), which was about four times higher than that of sphingosine.
      The potent agonist thrombin did not affect the total Sph-1-P amounts in platelet
      suspensions but induced the release of Sph-1-P stored in the cells into the
      medium.

PMID- 7503425
TI  - Soluble interleukin-5 receptor alpha-chain binding assays: use for screening and
      analysis of interleukin-5 mutants.
AB  - Interleukin-5 (IL-5) is a key cytokine for the production, differentiation, and
      activation of eosinophils. IL-5 is a member of the four helical bundle family of
      cytokines, and in common with many members of the cytokine family it binds to a
      heterodimeric receptor composed of a ligand binding alpha-chain and a signal
      transducing beta-chain. We have established two receptor/ligand binding assays
      based on the extracellular domain of the receptor alpha-chain which we have
      produced as a fusion protein. One assay is based on scintillation proximity
      fluoromicrospheres and radiolabeled ligand and the other on detection of
      biotinylated ligand binding to immobilized receptor using a chemiluminescent
      substrate in a 96-well microtiter plate format. Both receptor binding assays have
      been optimized for high throughput screening for receptor antagonists. These
      assays were also used for analytical purposes and the binding of ligand to the
      receptor alpha-chain was compared directly to receptor binding assays performed
      on TF-1 cells which express the receptor alpha beta-heterodimer. These three
      assays have been used to study site-directed mutants of IL-5 to determine the
      important residues for interaction of the cytokine with each chain of the
      receptor (P. Graber et al. (1995) J. Biol. Chem. 270, 15762-15769).

PMID- 7503426
TI  - Phosphate-specific fluorescence labeling of pepsin by BO-IMI.
AB  - Pepsin (3.6 nmol) was detected by the following three-step procedure: (i)
      reaction with a 20-fold molar excess of BO-IMI (a fluorophore containing a
      reactive imidazole group) in the presence of a 150-fold molar excess of 1-ethyl-3
      (3-dimethylaminopropyl)carbodiimide (EDC) and 2% sodium dodecyl sulfate; (ii) gel
      filtration (spin column) to remove most of the residual BO-IMI; and (iii)
      capillary electrophoresis with laser-induced fluorescence detection. For the
      latter step, 8.5 x 10(-7) of the original sample was injected. BO-IMI/EDC targets
      phosphomonoesters and does not label albumin (prior knowledge). Progressive
      dephosphorylation of pepsin with acid phosphatase reduced its labeling with BO
      IMI. Thus, the BO-IMI, as intended, labels the phosphate group on pepsin. Such BO
      IMI labeling should be useful in general for studying phosphoproteins and
      phosphopeptides.

PMID- 7503427
TI  - Enzymatic sialylation of N-linked oligosaccharides using an alpha-(2,3)-specific
      trans-sialidase from Trypanosoma cruzi: structural identification using a three
      dimensional elution mapping technique.
AB  - alpha-(2,3)-Sialylated biantennary and triantennary oligosaccharides were
      enzymatically prepared from pyridyl-2-amino-oligosaccharides with terminal Gal
      residues, using an alpha-(2,3)-specific trans-sialidase from Trypanosoma cruzi
      (Lee, K. B., and Lee, Y. C. (1994) Anal. Biochem. 216, 358-364). From the pyridyl
      2-amino-derivatives of neutral and alpha-(2,6)-monosialylated biantennary
      oligosaccharides from human fibrinogen, 5 different sialyl biantennary
      oligosaccharides were obtained. From two different asialo-triantennary
      oligosaccharides from fetuin, 35 sialyl oligosaccharides were obtained. The trans
      sialidase transferred sialic acids effectively and indiscriminately to different
      galactosyl residues in the different positions on the substrates. Since the
      starting materials are neutral oligosaccharide of established structure, and the
      only alpha-(2,3)-sialyl residues are added to the nonreducing Gal terminal
      residues, the structures of these oligosaccharides could be identified
      unambiguously by using the three-dimensional mapping technique (Takahashi, N.,
      Nakagawa, H., Fujikawa, K., Kawamura, Y., and Tomiya, N. (1995) Anal. Biochem.
      226, 139-146.) in combinations with strategic digestion with beta-galactosidase,
      beta-N-hexosaminidase, and sialidase L.

PMID- 7503428
TI  - Radiolabeling of small peptides bound to a solid phase.

PMID- 7503429
TI  - Simultaneous measurement of enzyme activity, protein, mRNA, and metabolites in
      small samples.

PMID- 7503431
TI  - Commercial [3H]glutamate contains a contaminant that labels tubulin covalently.

PMID- 7503430
TI  - Quantitative assay of trypsinogen by measurement of cleaved activation peptide
      after activation with enterokinase.
AB  - Measurement of trypsinogen by quantitative immunosorbent assay of the highly
      specific and inert trypsinogen activation peptide following complete activation
      of trypsinogen by enterokinase offers a simple and sensitive method that provides
      reliable results over a wide range of trypsinogen concentrations. This method
      offers a significant advantage in being applicable to complex biological tissues.

PMID- 7503432
TI  - Technical considerations for the use of ethidium bromide in the quantitative
      analysis of nucleic acids.

PMID- 7503433
TI  - Direct electroporation of DNA from in-gel ligation mixtures.

PMID- 7503435
TI  - Determination of surgeon-generated gown pressures during various surgical
      procedures in the operating room.
AB  - BACKGROUND: Patients' blood or other potentially infectious body fluids
      frequently pass through surgeons' gowns in the operating room. These fluids are
      absorbed by the scrub suit and can directly contaminate the surgeons' skin.
      Protective barriers remain an important method of exposure control for many blood
      borne pathogens. The efficacy of surgical gowns in preventing this passage or
      strikethrough has therefore become the focus of much attention. Limited data are
      available concerning the magnitude and duration of pressure against surgeons'
      gowns. METHODS: A 32-sensor mat placed in the abdominal area was used to obtain
      pressure data for 15 surgeons of both sexes performing 20 procedures. RESULTS:
      The percentage of time any pressure was detected varied from 0% during knee
      reconstruction to 97.4% for excision of a stomach mass. In 16 procedures, more
      than 87.8% of pressure contacts were 2 N/cm2 (2.9 psi or less); in addition, more
      than 80% of the contacts were 15 seconds or less during 13 of the procedures. No
      correlation was found between the amount of pressure and sex of the surgeon,
      surgical service, or length of the procedure. CONCLUSIONS: Because pressure is
      related to the type of procedure, gowns should be chosen to afford protection
      against fluid strikethrough for the pressures and blood loss anticipated.

PMID- 7503434
TI  - Compliance with universal precautions among health care workers at three regional
      hospitals.
AB  - OBJECTIVE: To assess and characterize self-reported levels of compliance with
      universal precautions among hospital-based health care workers and to determine
      correlates of compliance. DESIGN: Confidential questionnaire survey of 1716
      hospital-based health care workers. PARTICIPANTS: Participants were recruited
      from three geographically distinct hospitals. A stratified convenience sample of
      physicians, nurses, technicians, and phlebotomists working in emergency, surgery,
      critical care, and laboratory departments was selected from employment lists to
      receive the survey instrument. All participants had direct contact with either
      patients or patient specimens. RESULTS: For this study, overall compliance was
      defined as "always" or "often" adhering to the desired protective behavior.
      Eleven different items composed the overall compliance scale. Compliance rates
      varied among the 11 items, from extremely high for certain activities (e.g.,
      glove use, 97%; disposal of sharps, 95%) to low for others (e.g., wearing
      protective outer clothing, 62%; wearing eye protection, 63%). Compliance was
      strongly correlated with several key factors: (1) perceived organizational
      commitment to safety, (2) perceived conflict of interest between workers' need to
      protect themselves and their need to provide medical care to patients; (3) risk
      taking personality; (4) perception of risk; (5) knowledge regarding routes of HIV
      transmission; and (6) training in universal precautions. Compliance rates were
      associated with some demographic characteristics: female workers had higher
      overall compliance scores than did male workers (25% of female and 19% of male
      respondents circled "always" or "often" on each of the 11 items, p < 0.05); and
      overall compliance scores were highest for nurses, intermediate for technicians,
      and lowest for physicians. Overall compliance scores were higher for the mid
      Atlantic respondents (28%) than for those from the Southwest (20%) or Midwest
      (20%, p = 0.001). CONCLUSIONS: This study supports earlier findings regarding
      several compliance correlates (perception of risk, knowledge of universal
      precautions), but it also identifies important new variables, such as the
      organizational safety climate and perceived conflict of interest. Several
      modifiable variables were identified, and intervention programs that address as
      many of these factors as possible will probably succeed in facilitating employee
      compliance.

PMID- 7503436
TI  - Chickenpox outbreak among the staff of a large, urban adult hospital: costs of
      monitoring and control.
AB  - Chickenpox is a highly infectious disease of childhood, but there are increasing
      reports of occurrence in adults. A recent community epidemic of chickenpox
      resulted in 20 documented cases of adult chickenpox in a large metropolitan
      hospital. Nine of these cases resulted from direct exposure to an index patient
      and four were in tertiary contacts of the three index patients associated with
      the nosocomial outbreak. A total of 165.6 person-days of work were lost
      (estimated $18,000 cost) as a result of this outbreak, and 70 infection control
      unit person-hours were required during the investigation and control. This
      article reports a nosocomial epidemic and reviews guidelines for identification
      and control of adult chickenpox in a large hospital complex.

PMID- 7503437
TI  - APIC guideline for handwashing and hand antisepsis in health care settings.

PMID- 7503438
TI  - Clarification of equipment nomenclature.

PMID- 7503439
TI  - Clarification of equipment nomenclature.

PMID- 7503440
TI  - [Variability in occurrence, course and division into branches of renal arteries
      in human fetuses].
AB  - The existence and position of kidneys and suprarenal glands as well as the
      occurrence of the renal arteries were examined in 347 human fetuses between 3 and
      9 months of age. The studies on the course and division variability of the right
      and left renal arteries were performed in 220 fetuses. The investigations
      consisted in filling arteries with resin, X-raying and preparing. No absence of a
      kidney, suprarenal body and renal artery was disclosed. In 2 cases an abnormal
      position of the right kidney was stated. The renal arteries, both right and left,
      were most frequently running off from the aorta as single branches, the right one
      in 190 (86.4%) cases, the left in 152 (69%) cases. Two branches on the right side
      were recorded in 24 (10.9%) fetuses, and on the left side in 56 (25.5%) fetuses.
      Three renal branches were stated in 6 (2.7%) on the right side and in 12 (5.5%)
      fetuses on the left side. In 50.9% of cases the renal arteries were leaving the
      aorta symmetrically on the same level. In 32.7% the right renal artery was higher
      and in 2.7%, it was lower than the left one. The horizontal course from the aorta
      to the kidney hilus of the right renal artery was observed in 83 (37.7%) and of
      the left one in 99 (45%) of fetuses. In others the renal arteries were running
      less or more obliquely and downwards. The way, in which the right and left renal
      arteries are divided into branches, and also the departure places of renal
      suprarenal ramifications were so different that it is not possible to work out
      their classifications.

PMID- 7503441
TI  - [Stomatologic care requirement for 12-year old children in Poland].
AB  - The aim of this paper was to estimate the dentition status, periodontium and the
      occurrence of malocclusions, as well as to define the therapeutic requirements in
      this respect in 1380 children, aged 12 years, in Poland having been selected for
      studies by randomization. The children inhabited large and small towns as well as
      villages in 9 regions of Poland. The procedural method was based upon the rules
      of studies provided by World Health Organization, namely: "Oral Health Surveys
      Basic Methods of 1986." The rate of caries among 12-year-old children oscillated
      within the range of 90%, while the intensity of caries expressed by mean number
      of DMF claimed 4.37. The studied children had on the average each 2.7 teeth with
      active caries, 1.6 teeth filled, and 0.14 tooth removed due to caries. The index
      of treatment [equation: see text] was merely 0.36. Among the tested population
      70.5% of children required filling of defects, 8.9% endodontic treatment and
      11.4% extraction of teeth. Hardly 25.4% of 12-year-old children had healthy
      periodontium, but as many as 35.4% had dental calculi. Hence, improvement of the
      oral cavity hygiene was needed in 74.6% of children, therein 35.4% removal of
      tartar deposits. 37.2% of 12-year-old children were diagnosed to have
      malocclusions, 13.3% of them showed serious maxillo-occlusal abnormalities.

PMID- 7503442
TI  - [Clinical estimation of late treatment results in posttraumatic Sudeck's
      dystrophy treated with mannitol, calcitonin and exercise therapy].
AB  - The author presents late results of treating 60 patients with posttraumatic
      Sudeck's dystrophy of upper extremity. The treatment was conducted by 3 methods:
      30 patients were receiving mannitol for 1 month, 15 subjects were given
      calcitonin intramuscularly for 1 month, and programmed rehabilitation according
      to Mucha's scheme was applied in 15 patients. The results were estimated within
      the period of 1/2--2 years since the commencement of therapy. The evaluation of
      the results was accomplished by 3-degree classification namely: good, fair, poor.
      Main attention was focussed on the rest pain regression and improvement of the
      hand grasping function. In the total group of 60 patients under treatment, there
      were 38 persons with good results (62%), in 16 the result was fair (27%) and in 6
      persons the outcome was poor (11%). It has been recorded that the treatment
      during the I stage of disease by all the three methods used was uniformly
      effective. In the treatment of the II stage the most efficacious was mannitol
      (statistically significant). Mannitol best influenced the improvement of hand
      grasping strength after the treatment, as well as regression of DS typical
      changes in RTG and bone scan. It has been also ascertained that for achievement
      of good results--regardless of the therapeutic method--the greatest influence was
      exerted by: the time shorter than 3 months elapsing from the trauma to the onset
      of the treatment, initial deficit in flexion of the fingers smaller than 3 cm,
      the presence of typical for DS changes in bone scintigraphy as well as I stage of
      the disease.

PMID- 7503443
TI  - [Results of treating a late thrombosis in a vascular prosthesis after surgical
      repair of an aorto-femoral arterial segment with atherosclerosis].
AB  - During a four-year period from 1987-1990 as many as 43 patients were operated on
      at the Department of General and Vascular Surgery PMA, Szczecin for occluded
      aorto-femoral grafts. Late thrombosis occurred in 6.2% of patients who underwent
      aorto-femoral bypass grafting. That was the most frequent indication for
      reoperations. The author concludes that extra-abdominal graft thrombectomy via
      the groin, resection of the old anastomosis and insertion of a piece of new graft
      to the deep femoral artery produce the best clinical results. The cumulated index
      of patency of prostheses after 24 months was 38%.

PMID- 7503444
TI  - [Incidence of cholecystolithiasis in women employed by industrial workplaces in
      Szczecin].
AB  - Making use of the possibility that is provided by the ultrasonic technique
      applied for epidemiological examinations of cholelithiasis, 1339 women, aged 20
      69 years, employed at two "typical feminine" working places in Szczecin were
      investigated. The purpose of the paper was to perform sonographic studies of the
      gallbladders in women employed in "typical feminine" clothing industry
      establishments of Szczecin, in order to estimate the incidence rate of
      cholecystolithiasis in the studied population--types of cholelithiasis risk
      factors,--relationship between the changes revealed at sonographic examination
      and clinical symptoms. Cholelithiasis was diagnosed in 232 women, i.e. in 17.33%
      of the examined. The incidence rate was rising with the age from 1.66% of cases
      among those aged 20-29 years to 35.29% among women 60-69 years old. Successive
      significant risk factors appeared to be overweight in as many as 72.8% of the
      studied females with calculosis, and also past three or more pregnancies and
      miscarriages. The use of oral anticonceptive drugs as well as positive family
      anamnesis was of lesser, but of significant importance. Asymptomatic calculosis
      was disclosed in 173, whereas the other 273 studied women were found to have
      symptomatic calculosis. No relation was recorded between the number as well as
      the size of deposits in the gallbladders, and the presence of ailments or their
      absence. More frequent incidence of cholelithiasis in female population was
      encountered than that reported by West-European authors. Also more frequent
      appearance of symptomatic calculosis was evidenced than it is generally published
      in literature.

PMID- 7503445
TI  - [Clinical and electroneurographic changes in the peripheral nervous system of
      patients with chronic insulin-dependent diabetes (IDDM)].
AB  - The clinical and electro-neurographic examinations were carried out in 54
      patients aged 21-67 years (mean = 41.8) with IDDM of at least 10-year duration,
      and 25 subjects aged 19-62 years (mean = 39.0) as a control group. The aim of the
      study was the determination of: 1) the frequency of polyneuropathy appearance in
      patients with IDDM of at least 10-year duration; 2) the usefulness of
      electroneurography for detection of subclinical impairment of peripheral nervous
      system in diabetics; 3) the characterization of electro-neurographic
      abnormalities in diabetic neuropathy; 4) the influence of diabetes duration and
      metabolic control on severity of peripheral nerves affection; 5) the relationship
      between polyneuropathy and retinopathy, nephropathy and cataract occurrence in
      diabetic patients. Polyneuropathy was diagnosed--clinically in 67% of patients,
      electro-neurographically in 85% of patients. The neurographic study proved high
      sensitivity for detection of subclinical affection of peripheral nerves in
      diabetics. The electro-neurographic abnormalities appeared more frequently and
      were more considerable in the group of patients with clinical polyneuropathy.
      Frequency of the sensory and motor nerve fibres involvement was similar. The
      electroneurographical abnormalities corresponded with the features of mixed-
      axonal and demyelinating type of neuropathy. It was disclosed that the degree of
      neurographical changes did not depend on duration and severity of hyperglycemia
      in late period of the disease. A moderate relationship between occurrence of
      polyneuropathy and retinopathy, nephropathy as well as diabetic cataract was
      revealed.

PMID- 7503447
TI  - [Incidence of malignant lymphomas in Western Maritime Provinces in the years 1980
      1984].
AB  - Incidence rate of malignant lymphomas was determined in the population of Western
      Pomerania region. The period of studies covered the years from 1980 to 1984 and
      the patients being over 14 years old. In the Western Pomerania region malignant
      lymphoma was diagnosed during that period in 528 subjects: low grade malignancy
      lymphomas were diagnosed in 268, therein lymphocytic lymphomas 135, with high
      grade malignancy 54: malignant granulomatosis 125 cases and 77 plasmocytic
      myelomas. The following data were taken into consideration: sex, place of
      residence, type of lymphoma: in case of malignant granulomatosis also the
      histopathologic subtype, and in multiple myeloma the type of monoclonal protein.
      Szczecin Voivodeship was found to have the highest incidence rate of malignant
      lymphoma, namely 9,1/10(5) of inhabitants: in Koszalin and Gorzow Voivodeships
      respectively 6.9/10(5) and 6.1/10(5) of inhabitants annually. The difference in
      the incidence rate in Szczecin Voivodeship and two other ones was significant (p
      < 0.001). No significant differences in the morbidity existed between Koszalin
      and Gorzow Voivodeships. In the region there was a preporderance of malignant
      lymphomas in relation to malignant granulomatosis. Morbidity in malignant
      lymphoma more frequently involved men than women. Morbidity rate of lymphoma with
      low and high malignancy, as well as plasmocytic myeloma increases with the age.
      On the other hand, in malignant granulomatosis no statistically significant
      differences depending on the age and sex were recorded. The incidence rate in
      respective groups of malignant lymphoma was the highest in Szczecin, followed by
      other towns in the region, being the lowest in rural environment. In our region,
      with regard to all malignant lymphomas, the disease is more frequently diagnosed
      in the advanced clinical stage.

PMID- 7503448
TI  - [Analysis of mineral composition of femoral bones in the human fetus].
AB  - The actual paper presents the method and results of studies covering bone
      mineralization processes on the basis of analyzing selected elements. The aim of
      the study has been: 1) determination of the content of more important elements in
      fetal femoral bones, 2) thorough study of fluorine concentration changes in fetal
      bones at various fetal life period, 3) finding out whether there are
      statistically significant differences between the contents of elements forming
      the bone--at respective stages of fetal development. The material comprised 66
      femoral bones of human fetuses being of different age: Ca, Mg, Zn and Fe were
      determined with an atomic spectrophotometer, P colorimetrically, and F
      potentiometrically. The performed studies have revealed an increase of Ca and P
      with the age. Magnesium content was also rising, but less regularly. The process
      of fluorine cumulation was evidenced too. On the basis of the studies the
      following conclusions have been drawn, namely: The results of analyzing the bone
      mineral content furnish an insight into the course of the fetal skeletal
      formation process. Fluorine content in fetal femoral bones fails to correlate
      with the level of calcium and phosphate, which reflects the lack of evident
      influence exerted by fluorine upon the mineralization processes proceeding at
      this period of life. Placenta does not provide an effective barrier for fluorine
      transport into the bones of the growing fetus. Storage of anatomical specimens in
      preserving solutions may have an essential influence on the content of elements
      bound in labile manner with the bone mineral structure.

PMID- 7503446
TI  - [The role of dopamine neurotransmission on the development of ethanol dependence
      and course of abstinence syndrome].
AB  - This paper evaluates the influence of acute and chronic ethanol intoxication and
      withdrawal syndrome in rats and humans on central dopaminergic neurotransmission.
      Acute, low dose of ethanol (1.0 g/kg), produced a significant increase of
      dopamine level in rat's central nervous system (CNS) and decreased prolactin
      (PRL) level in blood serum. In chronic experiment rats were given the following
      dopaminergic agents: SKF 38393, PPHT, SCH 23393, Pimozide. Ethanol potentiated D1
      agonist features, whereas has no influence on D1 antagonist action in CNS, which
      reveals that chronic ethanol produced hypersensitivity of D1 receptors. Chronic
      ethanol potentiated pimozide action in behavioral tests. Chronic ethanol produced
      a decrease of compensatory augmentation of dopamine in rat's CNS after pimozide
      administration. PPHT, a potent D2 agonist normalized withdrawal symptoms in
      alcohol dependent rats. In the clinical part of experiment 21 alcohol dependent
      male individuals were examined for ethanol withdrawal syndrome, using DSM-III/R
      criteria, alcohol dependence index (WGU), and presence of dependence scale
      symptoms (WWO). The intensity of withdrawal symptoms was examined using Sandowal
      Wang scale. The level of blood serum PRL was also measured, twice a day (8 a.m.
      and 8 p.m.) on the 1st, 3rd, 7th, 14th, 21st day of experiment. It was
      established that WGU as well as WWO and DSM-III-R criteria did separate similar
      groups of patients with the same depth of dependence, clinical symptoms and
      prognosis. This study reveals a negative correlation between intensity of
      withdrawal symptoms and PRL levels in blood serum on the 1st day of abstinence.
      PRL levels were increased from 3rd to 21st day of study. Ethanol withdrawal
      symptoms intensity index was positively correlated with WGU.

PMID- 7503449
TI  - [Evaluation of the effect of radical parietal pleurectomy on ventilatory function
      of the lungs in patients treated for recurrent spontaneous pneumothorax].
AB  - Pleurectomy as a method for treatment of recurrent pneumothorax and its influence
      on pulmonary ventilation are analyzed. Fifty-one patients were hospitalised twice
      at the Thoracic Surgery Department in Szczecin. The pneumothorax was treated by a
      chest tube drainage at the first time, and by pleurectomy in case of recurrent
      incident. Each time--with both lungs expanded--VC (vital capacity), MVV (maximal
      voluntary ventilation) and FEV1 (forced expiratory volume) were measured, thus it
      was possible to compare pre- and postoperative spirometric results. There was no
      statistically significant deficiency of ventilation after pleurectomy. The risk
      of different therapeutical methods and effectiveness in the protection against
      recurrence of pneumothorax were discussed. The results of own observations are
      compared with other authors' ones.

PMID- 7503450
TI  - [Effectiveness of blood-testis and blood-epididymis barriers for lead].
AB  - Over the period of the last 30 years there was a marked decrease in the number of
      spermatozoa produced by the gonads of men. It is felt that this observation is
      due to the influence of environmental pollution, wherein the lead plays quite an
      important role. In sperms of men, who are professionally exposed to lead
      compounds, oligo-, asteno-, and teratospermia is disclosed. Studies were
      performed on sexually mature male rats after 9-month-long exposure to lead
      acetate (II) as well as a group of animals after 3-month-long interval in the
      exposure. The changes provoked by the lead were evaluated by employing a number
      of study techniques, namely: morphological examination of testes with taking into
      account the stages of seminiferous epithelial cycle, and epididymis, giving due
      consideration to zones; electron microscopic examination of seminiferous cells
      and interstitial tissue, as well as the cells in the wall of epididymis and
      spermatozoa; X-ray microanalysis determining the presence and type of elements on
      ultrathin section; spectrophotometrical determination of Pb content in blood,
      testes and epididymides; determination of testosterone concentration (T) in blood
      serum. It has been revealed that the blood-testis barrier protects seminiferous
      epithelium against the toxic action of the lead. No deposits of Pb were observed
      either in germinal cells or Sertoli cells. The endocrine testicular cells outside
      the barrier had also unchanged ultrastructure, and contained no Pb. That finding
      was expressed by normal T level in blood serum. The only cells in the area of the
      testis, in whose cytoplasm there was Pb confirmed by X-ray microanalysis, were
      macrophages in the interstitial tissue of the testis. Apart from that, it has
      been disclosed that the blood-epididymis barrier does not provide a barrier
      against this element. Pb deposits were seen in smooth myocytes, epithelial cells
      and in the lumen of epididymal duct. That correlated with a marked decrease in
      the number of epididymal spermatozoa and numerous damages involving their
      ultrastructure. It has been shown that the lead, when passing to the duct lumen
      of epididymis through cells and structures constructing the wall of that organ,
      is being excreted from the male genital system with the sperm.

PMID- 7503451
TI  - [Effect of unilateral nephrectomy on elimination of gentamicin in rabbits].
AB  - The aim of the paper was to study the effect of unilateral nephrectomy on
      gentamicin pharmacokinetics with special reference to elimination process. The
      study was performed on 19 male rabbits of Belgium race, divided into two groups:
      control and tested--subjected to nephrectomy. Pharmacokinetic determinations were
      accomplished in all the animals at the preliminary period, and after 2 weeks, and
      3 months following the operation; collecting the blood at time intervals of 6
      hours since intravenous administration of gentamicin at a dose of 3.5 mg/kg body
      mass, every 12 h, both after single and at steady state. The course of changes in
      concentration was described by means of an open one-compartment model for
      intravenous administration. The animals deprived of one kidney were found to show
      more intense defect in gentamicin elimination process than in the control group
      rabbits. The established results provide a practical conclusion, namely that in
      patients with one kidney only the necessity of decreasing the gentamicin dose
      should be taken into account, and, maybe, this can also refer to other drugs
      eliminated from the organism on the urinary system pathway. This finding is of
      particular significance involving the drugs with a narrow therapeutic coefficient
      and distinct toxicity for internal organs as well as hematopoietic system.

PMID- 7503452
TI  - [Effect of quercetin on the course of chronic poisoning with fluorine compounds
      in rats].
AB  - Biochemical examinations in serum, homogenates and microsomal fraction of the
      liver, as well as biochemical and morphological examinations of liver tissue were
      performed in rats of Wistar strain exposed chronically for 6 months to ammonium
      fluoride vapours. A part of animals was protected with a mixture of sodium salts
      of quercetin synthetized in Inorganic Chemistry Department of the Technical
      University at Rzeszow, and added to the standard feed in a dose of 5 and 20 mg/kg
      body weight. It has been disclosed that NH4F causes disturbances in the
      activities of enzymes (cholinesterases, transaminases, alkaline and acid
      phosphatase), a rise of bilirubin concentration in serum, as well as disturbances
      in lipid metabolism, an increase in the content of total lipids, and disorders of
      lipid metabolism--increase in the content of total lipids, cholesterol and
      triglycerides, with phospholipids being decreased. The biochemical changes are
      accompanied by the hepatic tissue lesion. The use of quercetin alleviates, to a
      considerable degree, the biochemical and morphological disturbances due to
      protracted exposure to ammonium fluoride vapours.

PMID- 7503453
TI  - [Comparative analysis of basic spirometric parameters accepted by various authors
      as values (norms) belonging to the same person, and an attempt to find values of
      these parameters that are proper for the population of young males in Poland].
AB  - Results of VC and FEV1 measurements in 283 males aged 18-40 years were the basic
      for "own standard" calculation. Measured values of VC and FEV1 obtained from
      males being tested were compared to values resulting from Baldwin, Berglund,
      Kory, Knudson, Morris, Nikodemowicz, CECA standards and own one. Measured values
      for VC did not differ from own standard and that of Morris. Measured values for
      FEV1 did not differ only from own standard, and were greater than all of the
      compared standards. According to both the standards of the discussed authors and
      own standard, due values of VC and FEV1 were found for "theoretical males" of 18
      40 years and height 150-195 cm. For these "theoretical males" the highest due
      values of VC were recorded in CECA nomogram, and due values of VC from own
      standard did not differ from Morris standard. Due FEV1 values from own standard
      were compatible with due values of CECA. It has been stated that for the
      assessment of spirometric tests for males aged 18-40 years in Poland, Morris
      standard should be currently accepted for VC values, and CECA standard for FEV1.

PMID- 7503454
TI  - [Influence of a high fat diet on the rabbit's heart muscle].
AB  - Changes having been caused during the application of high fat diet were estimated
      in the rabbit's heart muscle. The animals were divided into three groups. The
      control group was given the basic diet. The second group received high fat diet,
      while the third group got high fat diet and one of the 5 hypolipemic drugs (ME3,
      ME4, clofibrate, diprophylline, cernitin). The specimens from the left ventricle
      of the heart muscle were evaluated under light microscope for carrying out a
      number of histological and histochemical examinations, use was also made of
      electron microscopy. On the basis of the performed studies it has been
      ascertained that: 1) atherogenic diet in rabbits causes injury involving all the
      layers of the heart; 2) mechanism originating changes depends on vascular bed
      diminution, and on primary lesion of the mitochondrial system in cardiomyocytes;
      3) the used drugs with hypolipemic action fail to exert favourable influence upon
      the image of the damaged heart muscle.

PMID- 7503455
TI  - Introduction: wavelet transforms in biomedical engineering.

PMID- 7503456
TI  - Wavelets in biomedical engineering.
AB  - Wavelets analysis methods have been widely used in the signal processing of
      biomedical signals. These methods represent the temporal characteristics of a
      signal by its spectral components in the frequency domain. In this way, important
      features of the signal can be extracted in order to understand or model the
      physiological system. This paper reviews the widely used orthogonal wavelet
      transform method in the biomedical applications.

PMID- 7503457
TI  - Wavelet analysis of EEG for three-dimensional mapping of epileptic events.
AB  - This paper is aimed at understanding epileptic patient disorders through the
      analysis of surface electroencephalograms (EEG). It deals with the detection of
      spikes or spike-waves based on a nonorthogonal wavelet transform. A multilevel
      structure is described that locates the temporal segments where abnormal events
      occur. These events are then visually interpreted by means of a 3D mapping
      technique. This 3D display makes use of a ray tracing scheme and combines both
      the functional (the EEG but also its wavelet representation) and the
      morphological data (acquired from computed tomography [CT] or magnetic resonance
      imaging [MRI] devices). The results show that a significant reduction of the
      clinical workload is obtained while the most important episodes are better
      reviewed and analyzed.

PMID- 7503458
TI  - Multiresolution wavelet analysis of the body surface ECG before and after
      angioplasty.
AB  - Electrocardiographic recordings of patients with coronary artery stenosis, made
      before and after angioplasty, were analyzed by the multiresolution wavelet
      transform (MRWT) technique. The MRWT decomposes the signal of interest into its
      coarse and detail components at successively finer scales. MRWT was carried out
      on different leads in order to compare the P-QRS-T complex from recordings made
      before with those made after percutaneous transluminal coronary angioplasty
      (PTCA). ECG signals before and after successful PTCA procedures show distinctive
      changes at certain scales, thus helping to identify whether the procedure has
      been successful. In six patients who underwent right coronary artery PTCA,
      varying levels of reperfusion were achieved, and the changes in the detail
      components of ECG were shown to correlate with the successful reperfusion. The
      detail components at scales 5 and 6, corresponding approximately to the
      frequencies in the range of 2.3-8.3 Hz, are shown to be the most sensitive to
      ischemia-reperfusion changes (p < 0.05). The same conclusion was reached by
      synthesizing the post-PTCA signals from pre-PTCA signals with the help of these
      detail components. For on-line monitoring a vector plot, analogous to vector
      cardiogram, of the two most sensitive MRWT detail components is proposed. Thus,
      multiresolution analysis of ECG may be useful as a monitoring and diagnostic tool
      during angioplasty procedures.

PMID- 7503459
TI  - Multiscale analysis for singularity detection in pulmonary microvascular pressure
      transients.
AB  - This paper addresses the problem of pulmonary microvascular pressure estimation.
      The "why" and "how" of multiscale approaches in the context of singularity
      detection are discussed. From a linear viewpoint, the scalogram technique and the
      multiresolution representation for singularity detection are discussed in general
      under the wavelet framework. A technique as well as a criterion for the
      segmentation and the extraction of the region of interest or the optimal scale is
      proposed. A new nonlinear multiscale technique for singularity detection is also
      proposed. This multiscale representation is based on rank order filters and on
      mathematical morphology operators in particular. A scaling parameter is
      introduced for such operators as in the linear continuous wavelet transform
      leading to what we call morpholograms. Experiments performed on pulmonary artery
      pressure transients illustrate how the proposed technique can give a synopsis of
      the signal characteristics through the scales.

PMID- 7503460
TI  - Investigating the relationship between fetus EEG, respiratory, and blood pressure
      signals during maturation using wavelet transform.
AB  - In this study, we introduce the fast wavelet transform as a method for
      characterizing maturational changes in electrocortical activity, respiratory
      activity, and blood pressure in fetal lambs in early (110-122 days), mid (123-135
      days), and late (136-144 days) third trimester (term 145 days). Each recording
      was 2 hr in duration. Wavelet decomposition was performed for six sets of
      parameters D2j where 1 < or = j < or = 6. The six series wavelet transforms
      represent the following signal frequency bands: 1. 16-32 Hz; 2. 8-16 Hz; 3. 4-8
      Hz; 4. 2-4 Hz; 5. 1-2 Hz; 6. 0.5-1 Hz. In the early group, power in the
      electrocephalogram (EEG) was highest in the fourth wavelet band, with relatively
      low power in the other bands. Increase in gestational age was characterized by
      increased power in all four wavelet bands. Power in the first wavelet band was
      significantly increased during low-voltage fast activity (LVFA) in the late
      group. The respiratory and blood pressure signals showed common frequency
      components with respect to time and were coincident with the LVFA EEG signal.
      Respiratory activity was only observed during some of the LVFA periods and was
      completely absent during high-voltage slow activity (HVSA) EEG. The respiratory
      signal showed dominant power in the fourth wavelet band, and less power in the
      third and fifth band. The blood pressure signal was also characterized by
      dominant power in the fourth wavelet band. This power was significantly increased
      during periods of respiratory activity. These results suggest a strong
      relationship between fetal EEG, blood pressure, and breathing movements.

PMID- 7503462
TI  - Analysis of EEG transients by means of matching pursuit.
AB  - Matching pursuit (MP), a new technique of time-frequency signal analysis, was
      applied to simulated signals and the awake and sleep EEG. With the MP algorithm,
      waveforms from a very large class of functions were fitted to the local signal
      structures in a recursive procedure. By means of this technique, sleep spindles
      were localized in the time-frequency plane with high precision, and their
      intensities and time spans were found. The MP technique makes following the
      temporal evolution of transients and their propagation in brains possible. It
      opens up new possibilities in EEG research providing a means of investigation of
      dynamic processes in brains in a much finer time-frequency scale than any other
      method available at present.

PMID- 7503461
TI  - Investigating routes to chaos in the guinea-pig cochlea using the continuous
      wavelet transform and the short-time Fourier transform.
AB  - The continuous wavelet transform (CWT) and the short-time Fourier transform
      (STFT) were used to analyze the time course of cellular motion in the guinea pig
      inner ear. The velocity responses of individual outer hair cells and Hensen's
      cells to amplitude modulated (AM) acoustical signals applied to the ear canal
      displayed characteristics typical of nonlinear systems, such as the generation of
      spectral components at harmonics of the carrier frequency. Nonlinear effects were
      particularly pronounced at the highest stimulus levels, where half-harmonic (and
      sometimes quarter-harmonic) components were also seen. The generation of these
      components was consistent with the behavior of a dynamical system entering chaos
      via a period-doubling route. A negative-stiffness Duffing oscillator model
      yielded period-doubling behavior similar to that of the experimental data. We
      compared the effectiveness of the CWT and the STFT for analyzing the responses to
      AM stimuli. The CWT (calculated using a high-Q Morlet-wavelet basis) and the STFT
      were both useful for identifying the various spectral components present in the
      AM velocity response of the cell. The high-Q Morlet wavelet CWT was particularly
      effective in distinguishing the lowest frequency components present in the
      response, since its frequency resolution is appreciably better than the STFT at
      low frequencies. Octave-band-based CWTs (using low-Q Morlet, Meyer, and
      Daubechies 4-tap wavelets) were largely ineffective in analyzing these signals,
      inasmuch as the frequency spacing between neighboring spectral components was far
      less than one octave.

PMID- 7503463
TI  - Time delay estimation using wavelet transform for pulsed-wave ultrasound.
AB  - The windowed cross-correlation (WCC) technique has recently attracted attention
      in pulsed-wave (PW) ultrasound for measurement of tissue motion and blood flow
      velocity because of its performance advantages over the conventional Doppler
      method. The WCC measures tissue motion and blood flow velocity via estimation of
      time delays of backscattered signals in two consecutive echoes. In this paper, we
      propose a wavelet transform-based cross-correlation (WTCC) technique for the time
      delay estimation in PW ultrasound. The WTCC consists of three steps: (i)
      computing wavelet transforms (WTs) of received echoes, (ii) computing cross
      correlations in the wavelet domain, and (iii) estimating the time delays by
      maximizing the estimated cross-correlations. Dyadic or continuous wavelets may be
      used in the proposed approach. The WTCC has a unique feature of using varying
      time-frequency windows in processing compared with the WCC which only uses a
      single fixed window. Our computer simulations show that, compared with the WCC,
      the WTCC provides a better estimation of time delays (lower failure rate and
      lower estimate error) and its performance is more consistent under various
      conditions, and more robust with window size. In the simulations, we also tested
      a specific continuous wavelet for the WTCC that was the emitted pulse itself and
      found the corresponding WTCC outperforms the WTCC with a regular dyadic wavelet.

PMID- 7503465
TI  - Two applications of wavelets and related techniques in medical imaging.
AB  - We present two applications of wavelet and related techniques to problems arising
      in medical imaging. Both make considerable use of the edge detection and
      classification properties of wavelet-type representations. First we describe
      simple and effective techniques for image denoising and contrast enhancement
      based on the multiscale edge representation of images. These techniques are
      sufficiently flexible to successfully address the varying requirements posed by
      several different medical imaging modalities in common use today. Experimental
      results are presented to illustrate the application of these techniques to
      various types of medical images. Next we describe adapted waveform encoding, a
      technique for magnetic resonance imaging. One advantage of this technique is that
      it can be used to efficiently encode edge features of the object being imaged.
      This has a particular diagnostic application in tracking heart wall thickness
      during the cardiac cycle, which we present along with some experimental results
      along this line. We also present an analysis of the signal-to-noise ratios of
      images formed with this technique, as this is a factor of paramount importance in
      MRI. The fact that wavelet schemes tend to concentrate energy near edge features
      makes the result rather different than that found in standard Fourier based
      approaches. We indicate an exciting potential application of our technique:
      reducing spectral leakage in phosphorus spectroscopy.

PMID- 7503464
TI  - Optimal time-frequency projections for localized tomography.
AB  - An algorithm for recovering a function from essentially localized values of its
      Radon transform and sparse nonlocal values was outlined in Reference 13. That
      algorithm utilized the time-frequency properties of wavelets, coupled with the
      range theorems for the Radon transform, to localize essentially the dependence of
      the Radon transform. In this paper we utilize alternative time-frequency
      projections which were introduced by Coifman and Meyer (4). We present evidence
      that these bases are optimal according to our criterion for localized tomography.
      These bases require significantly less data than the wavelet bases that were used
      in Reference 13. Finally, we present numerical results supporting this work.

PMID- 7503466
TI  - Effect of cytochalasin D on the mechanical properties and morphology of passive
      human neutrophils.
AB  - The actin-rich cortex plays a major role in neutrophil chemotaxis and
      phagocytosis. In passive neutrophils, 30-50% of the actin molecules are in the F
      (filamentous) form, and it is the shifting of equilibrium with its monomeric G
      (globular) form that controls cell motility and phagocytosis. Cytochalasins have
      been shown to inhibit cell phagocytosis and ruffling. In purified actin,
      cytochalasins have been shown to decrease the amount of F-actin by capping the
      fast-growth end of actin filaments. Recent studies with intact cells, however,
      reveal that the most potent cytochalasin, cytochalasin D (CD), actually increases
      F-actin content suggesting that CD disrupts the actin network so as to increase
      the number of actin-filament ends for further actin polymerization. In this
      paper, we report the effects of CD on the passive mechanical behavior and
      morphology of human neutrophils with 1, 2, 10, and 20 microM CD. At 1 and 2
      microM CD, the cells remain spherical. However, in the presence of 10 and 20
      microM CD, cells are severely deformed and "blebby" as shown by light and
      scanning electron microscopy. After 1 and 2 microM CD treatment, the cells show a
      decrease of 43 and 66%, respectively, in cortical tension when measured by static
      micropipet aspiration experiments. Similarly, the cytoplasmic viscosities of 1
      and 2 microM CD-treated cells are decreased, but only by 17 and 24%,
      respectively. A proportionally greater effect on the cortical tension suggests
      that CD acts mainly on the actin-rich cortex by disrupting the filament network.

PMID- 7503467
TI  - Harmonic distortion from nonlinear systems with broadband inputs: applications to
      lung mechanics.
AB  - We present a simple index, extended harmonic distortion (kd), to represent the
      degree of system nonlinearity under sparse pseudorandom noise inputs (SPRN). The
      frequencies in a SPRN waveform are neither harmonics nor sums or differences of
      the other component frequencies. Expressed by percentage, the kd is the square
      root of the ratio of output power at non-input frequencies to the total output
      power. We evoke three simple corrections to recover the true kd under imperfect
      SPRN inputs. Simulations on two block-structured nonlinear models (Wiener and
      Hammerstein) demonstrate the necessity and effectiveness of these corrections
      especially for the Wiener-type nonlinearity. By applying kd to pressure-flow data
      of dog lungs, we found that the nonlinear harmonic interactions from a lung arise
      primarily from its tissues most likely the processes governing the tissue
      stiffness. This nonlinearity, assessed from kd, is stronger at higher tidal
      volumes and enhanced (but to a lesser degree) during bronchoconstriction. We
      conclude that since the kd approach avoids the necessity for multiple-input
      measurements and lengthy data records, it may be useful for tracking the dynamic
      variations in nonlinearities of a physiological system.

PMID- 7503469
TI  - Parameter estimation for a prosthetic ankle.
AB  - The mechanical parameters of a model of an energy storage and return ankle
      prosthesis are estimated for normal level walking by means of an optimization
      procedure. The walking cycle is divided into six fields, such that the power does
      not change sign within each field; the transition between successive fields
      occurs at zero power. The optimal spring stiffness as a function of time, is
      found by optimizing a quadratic cost function to minimize the difference between
      the estimated ankle moments and the moments in normal walking. The optimization
      is subjected to four continuous constraints within each field and to two
      continuity constraints for the transitions between successive fields. The time
      varying spring stiffness and the implications of additional external energy are
      discussed and are presented as recommendations for the designer.

PMID- 7503468
TI  - A model of transient oscillatory pressure-flow relationships of canine airways.
AB  - In a previous paper (27) we developed a lumped parameter model of canine
      pulmonary airway mechanics featuring airway wall elasticity, gas inertance, and
      laminar and turbulent gas flow. The model accurately accounted for the steady
      state pressure-flow data we obtained during sinusoidal cycling of the lung
      following a period of apnea. In the present paper, we extend the model to account
      for the transient decrease in the amplitude of the trans-airway pressure swings
      that we observed immediately following the apnea, which we have shown to be due
      to a vagally mediated bronchodilatation reflex. The extended model accounts for
      this transient in terms of a sudden change in airway smooth muscle tone acting on
      the viscoelastic properties of the airway wall and tissues mechanically coupled
      to it. Consequently, this model is able to temporarily store a volume of gas in
      the conducting airway tree as its volume changes cyclically with that of the
      whole lung. This means that the flow entering the airway tree from the trachea at
      any instant (V) is not precisely equal to that entering the alveoli (Valv) even
      when the gas is considered incompressible. We found that assuming V to be equal
      to Valv can lead to errors in estimating respiratory tissue impedance of as much
      as 10%. However, tissue hysteresivity remained almost unaffected, suggesting that
      the hysteretic properties of respiratory system tissues and airway wall are well
      matched.

PMID- 7503470
TI  - Biomechanical topography of human ankle cartilage.
AB  - The material properties of normal cadaveric human cartilage in the ankle mortice
      (tibiotalar articulation) were evaluated to determine a possible etiologic
      mechanism of cartilage injury of the ankle when an obvious traumatic episode is
      not present. Using an automated indentation apparatus and the biphasic creep
      indentation methodology, creep indentation experiments were performed in five
      sites in the distal tibia, one site in the distal fibula, and eight sites in the
      proximal talus of 14 human ankles (seven pairs). Results showed significant
      differences in the mechanical properties of specific human ankle cartilage
      regions. Topographically, tibial cartilage is stiffer (1.19 MPa) than talar
      cartilage (1.06 MPa). Cartilage in the anterior medial portion of the tibia has
      the largest aggregate modulus (HA = 1.34 MPa), whereas the softest tissue was
      found to be in the posterior lateral (0.92 MPa) and the posterior medial (0.92
      MPa) regions of the talus. The posterior lateral ridge of the talus was the
      thickest (1.45 mm) and the distal fibula was the thinnest (0.95 mm) articular
      cartilage. The largest Poisson's ratio was found in the distal fibula (0.08). The
      lowest and highest permeability were found in the anterior lateral regions of the
      astragalus (0.80 x 10(-15) m4N-1sec-1) and the posterior medial region of the
      tibia (1.79 x 10(-15) m4N-1sec-1), respectively. The anterior and posterior
      regions of the lateral and medial sites of the tibia were found to be 18-37%
      stiffer than the anatomically corresponding sites in the talus. The biomechanical
      results may explain clinically observed talar dome osteochondral lesions when no
      obvious traumatic event is present. Cartilage lesions in a repetitive overuse
      process in the ankle joint may be related to a disparity of mechanical properties
      between the articulating surfaces of the tibial and talar regions.

PMID- 7503471
TI  - A cost-effectiveness analysis of screening and treatment for Chlamydia
      trachomatis infection in asymptomatic women.
AB  - OBJECTIVE: To assess the cost-effectiveness of identifying and treating
      asymptomatic female carriers of Chlamydia trachomatis. DESIGN: Cost-effectiveness
      analysis based on previously reported cohort analytic studies and average
      salaries and costs of medical care in Sweden. SETTING: Women attending youth,
      family planning, and gynecology clinics. PARTICIPANTS: 1000 women and their male
      sex partners. INTERVENTION: Screening with tissue cell culture, confirmed enzyme
      immunoassay, and DNA amplification assays based on either polymerase chain
      reaction or ligase chain reaction was compared with no screening (no treatment
      and no tracing of sexual contacts). The effect of antibiotic regimens on the
      outcome of the screening strategies was also evaluated. RESULTS: When the
      prevalence of chlamydial infection exceeded 6%, screening of women with DNA
      amplification assay and treatment of positive patients with a single oral dose of
      azithromycin given under supervision in the clinic was the most cost-effective
      intervention strategy. At greater prevalences, screening with enzyme immunoassay
      also generated savings and improved the cure rates compared with no screening,
      but such screening was less cost-effective than screening with a DNA
      amplification assay. Compared with no intervention, tissue cell culture is cost
      effective only when the prevalence of infection is greater than 14%. Compared
      with the azithromycin regimen, the standard 7-day, twice-daily doxycycline
      regimen resulted in significantly lower cure rates because of patients' poor
      compliance with this regimen. CONCLUSION: For asymptomatic female carriers of C.
      trachomatis, screening with a DNA amplification assay combined with the single
      dose azithromycin treatment of positive patients is the most cost-effective
      strategy when the prevalence is 6%. When the prevalence is lower than 6%, the
      decision to choose a competing strategy depends on the physician's view of the
      value of preventing an illness caused by untreated chlamydial infection.

PMID- 7503472
TI  - Cardiac event recorders yield more diagnoses and are more cost-effective than 48
      hour Holter monitoring in patients with palpitations. A controlled clinical
      trial.
AB  - OBJECTIVE: To compare the diagnostic yield and cost-effectiveness of
      transtelephonic event monitors with those of Holter monitoring in patients with
      intermittent palpitations. DESIGN: Randomized crossover trial. SETTING:
      Diagnostic service of a teaching hospital and surrounding primary care practices.
      PATIENTS: 43 patients with previously uninvestigated palpitations who were
      referred for Holter monitoring. MEASUREMENTS: Patients were randomly allocated to
      receive an event monitor or 48-hour Holter monitor and then to receive the other
      device. Event monitors were used for 3 months or until two recordings were
      obtained while symptoms occurred. The main end point was an electrogram recorded
      during symptoms. The incremental cost-effectiveness of obtaining a diagnostic
      rhythm strip from event monitors was compared with that of Holter monitoring.
      RESULTS: The mean (+/- SD) patient age was 45 +/- 19 years; 37 patients (88%)
      were women. Event monitors were twice as likely to provide a diagnostic rhythm
      strip electrocardiogram during symptoms as 48-hour Holter monitoring (29 patients
      [67%] and 15 patients [35%], respectively; P < 0.001). Event monitors detected 8
      patients (19%) with clinically important arrhythmias (6 patients with
      supraventricular tachycardia and 2 with atrial fibrillation or flutter), whereas
      the Holter monitors detected no significant arrhythmia (P < 0.005). With the
      event monitors, most patients transmitted an electrocardiogram recording by 6
      weeks. Event monitors were dominant and therefore more cost-effective than 48
      hour Holter monitoring, resulting in a cost savings of $213 for each additional
      diagnostic rhythm strip obtained during symptoms. CONCLUSIONS: Holter monitoring
      is a poor diagnostic test for intermittent palpitations. Event recorders provide
      better data and are more cost-effective.

PMID- 7503473
TI  - The effect of multiple neuroimaging studies on classification, treatment, and
      outcome of acute ischemic stroke.
AB  - OBJECTIVE: To examine the effect of serial neuroimaging studies on the diagnosis,
      therapy, and outcome of patients with acute stroke. DESIGN: Retrospective case
      series. SETTING: Tertiary care teaching hospital. PATIENTS: 206 adult patients
      (mean age +/- SD, 66.0 +/- 10.8 years) hospitalized with a diagnosis of acute
      stroke between 1990 and 1993. MEASUREMENTS: Strokes were retrospectively assigned
      to five categories (large-vessel, small-vessel, cardioembolic, other, or unknown)
      using standardized criteria based on the history, physical examination, ancillary
      test results, and first computed tomographic (CT) or magnetic resonance imaging
      (MRI) study of the head. Strokes were reclassified after the results of further
      neuroimaging studies, if any, were reviewed. The type and timing of therapy and
      the patient outcome at hospital discharge were documented. RESULTS: The
      additional studies changed stroke classification in only 20.0% of the 140
      patients who had two or more neuroimaging studies. All classification changes
      were from the unknown cause category to a category with a specific cause. In most
      patients receiving treatment (93.2%), therapy began before an additional CT or
      MRI study was obtained. In patients who had one neuroimaging study, 70.1% went
      home, 24.0% went to a skilled nursing facility, and 5.9% died; the corresponding
      percentages in persons who had multiple studies were 73.3%, 24.4%, and 2.2% (P >
      0.1). CONCLUSIONS: Serial neuroimaging studies did not alter the classification
      of strokes for which an initial diagnosis had already been made. However, they
      were useful in determining the cause of strokes initially classified as having an
      unknown cause. Therapy was almost always begun immediately after the first CT or
      MRI study was obtained. Outcome at hospital discharge was not significantly
      related to the number of neuroimaging studies obtained.

PMID- 7503474
TI  - Bell palsy and herpes simplex virus: identification of viral DNA in endoneurial
      fluid and muscle.
AB  - OBJECTIVE: To determine whether herpes simplex virus type 1 (HSV-1) causes Bell
      palsy. DESIGN: Prospective study. SETTING: University inpatient service.
      PATIENTS: 14 patients with Bell palsy, 9 patients with the Ramsay-Hunt syndrome,
      and 12 other controls. MEASUREMENTS: Viral genomes of HSV-1, varicella-zoster
      virus, and Epstein-Barr virus were analyzed in clinical samples of facial nerve
      endoneurial fluid and posterior auricular muscle using polymerase chain reaction
      (PCR) followed by hybridization with Southern blot analysis. RESULTS: Herpes
      simplex virus type 1 genomes were detected in 11 of 14 patients (79%) with Bell
      palsy but not in patients with the Ramsay-Hunt syndrome or in other controls. The
      nucleotide sequences of the PCR fragments were identical to those of the HSV-1
      genome. CONCLUSIONS: Herpes simplex virus type 1 is the major etiologic agent in
      Bell palsy.

PMID- 7503475
TI  - Hepatitis C virus genotype analysis in patients with type II mixed
      cryoglobulinemia.
AB  - OBJECTIVE: To investigate the possible role of HCV variants in the pathogenesis
      of mixed cryoglobulinemia. SETTING: Medical service (rheumatology and hepatology
      units) of urban, university-affiliated teaching hospitals. DESIGN: Analysis of
      viral genotypes in a cohort of patients with hepatitis C virus (HCV) infection
      and mixed cryoglobulinemia. PATIENTS: 90 unselected HCV-positive (anti-HCV
      antibody-positive and HCV RNA-positive) patients consecutively recruited at
      routine ambulatory visits: 29 with and 61 without (control group) mixed
      cryoglobulinemia. MEASUREMENTS: Clinical and histologic data; HCV RNA detection
      in serum and peripheral blood mononuclear cells by polymerase chain reaction
      (PCR); HCV genotype determination by two methods based on genotype-specific
      primer PCR and genotype-specific probe hybridization, respectively. RESULTS:
      Persistent aminotransferase increases were found in 55% of patients with mixed
      cryoglobulinemia. Peripheral blood mononuclear cells were infected in 80% of
      cases. In serum samples, HCV genotype 2a/III was detected with a higher
      prevalence in patients with mixed cryoglobulinemia than in controls (41% compared
      with 15%). The overall prevalence of genotype 2a/III in mixed cryoglobulinemia
      increased to 52% when findings in peripheral blood mononuclear cells were also
      considered. Among patients with mixed cryoglobulinemia, this genotype was more
      frequent in those without clinical and biochemical signs of liver disease (85%)
      or with serum autoantibodies (75%). CONCLUSIONS: Mixed cryoglobulinemia may be
      related, at least in part, to the HCV genotype infecting the host.

PMID- 7503476
TI  - Adult immunizations.
AB  - New vaccines have been licensed for hepatitis A, varicella, and typhoid. This
      paper reviews these vaccines and their recommended uses in adults. Special
      attention is given to a new national policy establishing age 50 years as a time
      for review of preventive health measures with emphasis on evaluating risk factors
      that indicate a need for pneumococcal vaccine and the initiation of annual
      influenza immunization.

PMID- 7503477
TI  - Impaired exercise tolerance in hypertensive patients.
AB  - PURPOSE: To review information on exercise testing in hypertensive patients and
      persons at risk for developing hypertension and to determine whether this type of
      investigation is valuable for diagnosis, prognosis, or assessment of the effect
      of therapy. DATA SOURCES: A MEDLINE search of English-language articles published
      between 1985 and 1995 and reviews of the bibliographies of textbooks. STUDY
      SELECTION: Primary research articles on exercise testing in patients with
      hypertension, with an emphasis on methods, diagnosis, prognosis, and assessment
      of drug therapy. DATA EXTRACTION: Study design and quality were assessed, with
      particular attention paid to methods and aims. Relevant data on hemodynamic
      responses in hypertensive patients and persons at risk for developing
      hypertension and correlations to end-organ damage, mortality, and exercise
      tolerance were analyzed. DATA SYNTHESIS: The exercise capacity of hypertensive
      patients was found to be reduced by as much as 30% compared with age-matched
      controls. This exercise impairment increases with age and end-organ damage, and
      its origin can be traced back to adolescence. Total peripheral resistance also
      progressively increases. These changes are caused by functional and structural
      involvement of the cardiovascular system. Diastolic dysfunction of the heart is a
      prominent factor in this exercise limitation. The blood pressure responses to
      exercise have prognostic value for the future development of hypertension, end
      organ damage, and death. The adequacy of antihypertensive treatment should
      therefore be evaluated in terms of normalizing these stress-related blood
      pressure responses. CONCLUSION: Exercise testing is a simple procedure that has
      great potential for assessing hypertensive patients. More research is necessary,
      however, to determine whether controlling blood pressure during exercise is
      beneficial.

PMID- 7503478
TI  - Medical heuristics: the silent adjudicators of clinical practice.
AB  - Robust scientific conclusions are too sparse to inform fully most of the choices
      that physicians must make about tests and treatments. Instead, ad hoc rules of
      thumb, or "heuristics," must guide them, and many of these are problematic.
      Physicians extrapolate from the small samples studied by clinical trials to
      general populations, but they do so inconsistently. Many physicians live by rules
      that dictate "not treating the numbers," correcting abnormalities slowly,
      achieving diagnostic certainty, and operating now to avoid "greater" risk in the
      future. Yet in each case, historical trends or statistical realities suggest
      either doing the opposite or investing in more discriminating heuristics. The
      heuristics of medicine should be discussed, criticized, refined, and then taught.
      More uniform use of explicit and better heuristics could lead to less practice
      variation and more efficient medical care.

PMID- 7503479
TI  - Herpes simplex virus and Bell palsy.

PMID- 7503480
TI  - Control, complications, confidence: the Regenstrief Conference on the risks and
      benefits of intensive management in NIDDM.

PMID- 7503481
TI  - Annals now and then.

PMID- 7503482
TI  - Peak of the season.

PMID- 7503483
TI  - Hepatic hepatitis C virus RNA in chronic hepatitis C.

PMID- 7503484
TI  - Folic acid and methotrexate in rheumatoid arthritis.

PMID- 7503485
TI  - Folic acid and methotrexate in rheumatoid arthritis.

PMID- 7503486
TI  - Folic acid and methotrexate in rheumatoid arthritis.

PMID- 7503487
TI  - Increase in serum free thyroxine levels related to intravenous heparin treatment.

PMID- 7503488
TI  - CPR-not-indicated and futility.

PMID- 7503489
TI  - CPR-not-indicated and futility.

PMID- 7503490
TI  - CPR-not-indicated and futility.

PMID- 7503491
TI  - CPR-not-indicated and futility.

PMID- 7503492
TI  - CPR-not-indicated and futility.

PMID- 7503493
TI  - CPR-not-indicated in futility.

PMID- 7503494
TI  - CPR-not-indicated futility.

PMID- 7503495
TI  - CPR-not-indicated futility.

PMID- 7503496
TI  - Physician compliance with guidelines.

PMID- 7503497
TI  - Suppression of subclinical shedding of herpes simplex virus type 2 with
      acyclovir.
AB  - OBJECTIVE: To assess the effect of the antiviral drug acyclovir on the frequency
      of subclinical shedding of herpes simplex virus (HSV) in the genital tract.
      DESIGN: A double-blind, placebo-controlled, crossover clinical trial. SETTING: A
      university-based virology research clinic. PATIENTS: 34 women with herpes simplex
      virus type 2 (HSV-2) antibody only and genital herpes of less than 2 years'
      duration. INTERVENTION: Participants were randomly assigned to receive either
      acyclovir, 400 mg twice daily for 70 days, followed by a 14-day washout period,
      and then placebo for 70 days, or the study medications in the reverse order.
      MEASUREMENTS: Women collected daily genital swabs of the vulvar, cervicovaginal,
      and perianal areas for HSV culture, maintained a diary of genital lesions, and
      were examined at the time of recurrences. RESULTS: In an intent-to-treat analysis
      of the initial treatment period, 15 of the 17 women who received placebo and 3 of
      the 17 women who received acyclovir had at least 1 day of subclinical shedding (P
      < 0.001). Among the participants who received placebo, subclinical shedding
      occurred on 64 of 928 (6.9%) days compared with 3 of 1057 (0.3%) days among the
      participants who received acyclovir (P < 0.001). The relative risk for
      subclinical shedding was 0.09 (95% CI, 0.03 to 0.35) for the women who received
      acyclovir compared with the women who received placebo. In a paired analysis of
      26 women who completed both arms of the study, acyclovir therapy was associated
      with a decrease in the frequency of subclinical shedding; subclinical shedding
      occurred on 83 of 1439 (5.8%) days with placebo, and on 6 of 1611 (0.37%) days
      with acyclovir (P < 0.001)--a 94% reduction. The frequency of subclinical
      shedding was reduced at all anatomic sites and in all patients. CONCLUSIONS:
      Daily therapy with oral acyclovir suppresses subclinical shedding of HSV-2 in the
      genital tract, suggesting that studies to evaluate the use of acyclovir in
      preventing HSV-2 transmission are warranted.

PMID- 7503498
TI  - [Phonetic results after surgery of laryngotracheal stenoses in children].
AB  - The quality of the results of laryngotracheoplasties is clear evidence of the
      progress made in the treatment of stenoses involving the larynx and the trachea
      in children. the surgeon is no longer limited to helping the child breath
      correctly via the natural airways but can also concentrate on phonatrics since
      dysphonia is frequent after laryngotracheoplasty. Vocal production of 23 children
      who had undergone surgery for laryngotracheal stenosis was evaluated subjectively
      by a panel of listeners and objectively on the basis of the pitch and intensity
      of the voice, rate of speech and maximal time of phonation. In 11 children over
      the age of 5 years, assisted assessment of the voice completed the study. In
      69.5% of the cases, the voice was subjectively considered to be satisfactory.
      Voice was considered clear in 52% of the cases. Speech flow was impaired in 39%
      due to frequent breath taking. Objective parameters revealed that pitch was
      slightly impaired (256 Hz) with a tendancy to normalize near puberty. The
      intensity of the voice (77 dB) and mean maximum phonation time (7 s) decreased.
      The phonotary quotient (270 ml/sec), jitter (1.4%) and leakage of the glottis
      (2.02 cm3/dB/s) were slightly above the normal range. The spectra of the voices
      were richly furnished with harmonics up to about 1 000 Hz above which air noises
      increased. An attempt was made to correlate the analysis of the voice with the
      characteristics of the stenosis and with the therapeutic methods used. The
      results would suggest the iatrogenic nature of prolonged canulation and of
      increasing the size the size of the posterior cricoid.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7503499
TI  - [Reconstructive anterior frontal laryngectomy. Long-term results in T2 glottic
      cancers].
AB  - Between 1982 and 1992, we performed near total laryngectomy with epiglottic
      reconstruction in 142 patients with state T1 and T2 according to the 1987 Union
      Internationale contre le Cancer. In this paper, we report our experience with 61
      T2 patient who were followed-up 5 years or until death. Actuarial survival was
      83%. Actuarial tumor control was obtained in 91%. There were no post-operative
      mortalities and follow-up was usually simple. All patients underwent decanulation
      and were able to eat by normal track. The main drawback of this technique is
      speech disability. We use near total laryngectomy with epiglottic reconstruction
      in certain T2 patients selected according to local extension. This choice is
      justified by good functional results and an excellent local control. The
      contraindications are age over 75 years, poor patient cooperation, cardiac or
      pulmonary disease, fixation of the arytenoids, subglottic extension of more than
      1 cm in front and 0.5 cm laterally, and extensive involvement of the ventricular
      folds or anterior commissure.

PMID- 7503500
TI  - [Analysis of complications of thyroid surgery: recurrent paralysis et
      hypoparathyroidism. On a series of 588 cases].
AB  - The purpose of this report is to study the incidence of two main complications in
      thyroid surgery without systematic search for recurrent laryngeal nerve, by
      intracapsular thyroidectomy: temporary and chronic laryngeal recurrent paralysis
      (after six months), temporary hypoparathyroidism and chronic hypoparathyroidism
      (unrecovering normal function after six months). We have retrospectively analysed
      588 patients from 1981 to 1994. There were 247 total or subtotal thyroidectomies
      and 341 loboisthmectomies (isolated thyroid nodules). We obtained over this 588
      cases 0.3% of chronic laryngeal paralysis and 1.4% of chronic hypoparathyroidism.
      If the cost of surgery for thyroid nodules is low (0.3% of chronic recurrent
      paralysis and 0% of chronic hypoparathyroidism), it is more important for total
      or subtotal thyroidectomies (respectively 1.2% and 3.2%). We conclude that in
      thyroid surgery, there is no higher risk for the recurrent nerve without
      dissection of this one, but we note that, without obvious explanation, rates of
      permanent hypoparathyroidism are not better than in others publications.

PMID- 7503501
TI  - [Clinical and surgical aspects of cysts and fistulae of the nose in children.
      Apropos of 37 cases].
AB  - Thirty-seven children with nasal midline masses and/or sinus ostia were
      surgically treated in the pediatric ENT and cervicofacial surgery department of
      Trousseau children hospital in Paris, from 1974 to 1994. The patients presented
      with midline cysts (11 cases), sinus ostia (8 cases) or both (18 cases). Various
      surgical techniques were used ranging from transcolumellar approach (25 cases) to
      direct midline approach (8 cases) or paracanthal approach. Preoperative imagery
      and surgery showed in 6 patients an intracranial extension to the base of the
      foramen cecum, without intracranial mass. Histologic examination demonstrated 33
      dermoids, 1 lipoma, 1 hamartoma, 1 glioma ans 1 hemangioma. 2 recurrences
      occurred after surgery. In children, the transcolumellar approach provides an
      enhanced exposure with a few percentage of recurrences and good cosmetic results.

PMID- 7503502
TI  - Circulating auto-antibodies in Meniere's disease.
AB  - In the last years, it has been claimed that patients suffering from Meniere's
      disease exhibit Circulating Immune Complexes, as well as free antibodies
      specifically directed against type II collagen, a component of the mammal inner
      ear. Furthermore, by means of repeated injections of type II collagen to the
      guinea-pig. Meniere's disease has been reproduced. Taken together, all these
      features strongly suggest that Meniere's disease fulfills most of the postulates
      that Witebsky established for the classification of auto-immune diseases.
      However, in spite of being a very well known marker of auto-immune conditions,
      non organ nor species specific Circulating Auto-Antibodies (CAA) have not been
      reported, to our knowledge, in Meniere's disease. Based upon this fact, Anti
      Nuclear, Anti-Mitochondrial, Anti-Smooth Muscle, Anti-LKM and Anti-Parietal
      Gastric Cells Auto-Antibodies have been investigated in 49 patients diagnosed as
      having Meniere's disease according to the criteria of the AAOO. All of them were
      asymptomatic at the time of the study. Seventy eight serum samples from Normal
      Healthy Subjects (NHS) constituted the control group. CAA were tested by indirect
      immunofluorescence on rat organs according to the method described by Coons.
      Additionally, the seric levels of C3, and C4 as well as the haemolytic capacity
      (CH-50) of the serum samples were tested. Furthermore, Circulating Immune
      Complexes (CIC) as well as the Complement-Mediated Mechanisms involved in the
      clearance of CIC (Complement-Mediated Solubilization and Inhibition of the Immune
      Precipitation) were investigated in parallel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503503
TI  - [Contribution of echography in the detection of lymph node diseases in epidermoid
      carcinoma of the larynx: therapeutic implications].
AB  - Based on a clinical, echographic and histologic study of 80 lymph node
      dissection, correlations were made by dissection and lymph node localization. The
      literature and the results of this study suggest that preoperative echography
      could have an effect on the surgical procedure, especially in cases with a
      clinically detected lymph node enlargement and if complementary radiotherapy is
      planned.

PMID- 7503504
TI  - [Primary non-Hodgkin lymphoma of the nasal fossae and sinuses. Apropos of 8
      cases].
AB  - The authors report their experience about 8 cases of nasal lymphomas diagnosed
      and treated between 1987 and 1993. Behind ordinary symptoms, a very bad forecast
      lymphoma may be hidden. Histological diagnosis is sometimes difficult and needs
      voluminous fresh fragments. During the evolution of this affection, local
      temporary nasal and paranasal remissions are often noted after chimiotherapy
      and/or radiotherapy, but rapidly appear visceras secondary localisations,
      suggesting an underestimation of the nasal and paranasal sinuses localisations
      among the treated non-Hodgkin's lymphomas population.

PMID- 7503505
TI  - [Allografts in otology. Potential risk of prion contamination. Current status of
      knowledge and legislation].
AB  - The potential risk of prion contamination has led the government authorities to
      stop the use of dura mater allografts of human origin. The aim of this work was
      to determine the potential risk for implantation of allografts in otology and to
      review the current reglementation. Although Creutzfeldt-Jakob's disease has not
      been reported to be transmitted by these allografts and despite the apparently
      rigorous decontamination methods used by the manufacturers which meet the most
      severe international recommendations, it is apparently necessary to stop
      implantation for the time being. This decision has resulted from the lack of a
      precise directive from the governmental authorities and the uncertainty about
      prion transmission and the reel effect of inactivation procedures.

PMID- 7503506
TI  - [Bucco-sinusal site of primary leiomyosarcoma].
AB  - The leiomyosarcoma, a malignant smooth muscle tumor, is common in uterus and
      gastro intestinal track. Only 27 cases of oral cavity localisation have been
      report in literature since 1908. We report a case of primary leiomyosarcoma of
      palate in 26 years old woman. The diagnosis is made by histopathological
      examination after biopsy. The extension is revealed by clinical symptoms and scan
      examination. The treatment is based on wide surgery Chemotherapy and radiotherapy
      could be proposed. The prognosis of the lesion depends of metastatic development,
      few cases have been present with metastases developed after one year, two years
      and five years. Generally their localisation are liver, lungs or lymph nodes. In
      our case after two years post operative a second lesion is revealed and the
      patient died quickly.

PMID- 7503507
TI  - [Molecular genetics of familial and sporadic forms of human prion diseases].
AB  - Prion diseases, also known as transmissible subacute spongiform encephalopathies
      (TSSE), are rare neurodegenerative disorders of both humans and animals. Their
      biochemical hallmark is an accumulation in the brain of an abnormal form of the
      host-encoded prion protein (PrP). This pathological accumulation could result
      from a protein conformational change under the influence of unknown factors. The
      normal function of PrP is unknown. The abnormal form is thought to induce
      neurodegeneration when experimentally or accidentally introduced in recipient
      hosts. Such a possibility would explain the transmissible character of these
      diseases illustrated in humans by iatrogenic contamination. Considerable
      attention has been focused on the host PrP gene and its relation with the genetic
      susceptibility of humans and animals. Mutations in PRNP, the gene which encodes
      PrP in humans, are present in 17% of the patients and might be causative. In
      patients without any PRNP mutation, a coding polymorphism (129 Met/Val) defines a
      predisposing factor. Important progress in the molecular genetics of TSSE in both
      humans and animals have been performed for few years and point out that the
      development of different forms of these diseases, experimental, iatrogenic or
      spontaneous, are strongly dependent on the primary structure of the host PrP.

PMID- 7503508
TI  - [Potassium channel activators: comparative structural study of pinacidil,
      diazoxide and cromakalim].
AB  - A conformational analysis has been performed with SYBYL starting from the energy
      optimized (Tripos force field) X-ray conformation of (R,S)-pinacidil. The
      geometry of four selected low energy conformers has been reoptimized using the
      AM1 semiempirical Molecular Orbital method (MOPAC 5.0), and the total energy of
      the optimized conformers has been compared. In spite of an apparent structural
      dissimilarity, a good analogy has been found between the calculated isopotential
      map of diazoxide and that of at least one selected low energy conformer of
      pinacidil. It has been suggested that, unlike cromakalim, the low but observable
      activity of pinacidil on pancreatic B-cells could be explained by adoption for
      this compound of a conformation having a diazoxide-like stereoelectronical
      imprint which could assume a similar interaction on the same biological receptor.

PMID- 7503510
TI  - [Psychopharmacological study of two 3-arylsulfonyl 4-hydroxy-coumarines].
AB  - The pharmacological study of 3-(4-chlorophenylsulfonyl) 4-hydroxy-7-methoxy-
      coumarine and 3-(4-methylphenylsulfonyl) 4-hydroxy-7-methoxy-coumarine shows that
      these derivatives present low sedative effects on the central nervous system,
      particularly due to their actions upon temperature and motility, more accentuated
      for the chloro-substituted derivative.

PMID- 7503509
TI  - [Synthesis and structural study of 5-arylidene thiazolidine-2,4-diones and 3
      substituted-4-thio-imidazolidine-2-ones].
AB  - The synthesis and the physico-chemical properties of four 3-(4-bromophenacyl)-5
      arylidene-thiazolidine-2,4-diones, two 3-(4-bromobenzyl)-5-arylidene-thiazolidine
      2,4-diones and seven 3-(4-chlorobenzyl)-5-arylidene-4-thio-imidazolidine-2-ones
      were described. These products were synthetized by the aldolisation-crotonisation
      reaction between aromatic aldehydes and substituted thiazolidinediones or thio
      imidazolidinones.

PMID- 7503511
TI  - Properties of red blood cell concentrates stored in PAGGS-sorbitol.
AB  - The physiological, biochemical, morphological and rheological characteristics of
      RBC resuspended in PAGGS-Sorbitol were studied over, and beyond, 49 days. The
      levels of P50 and 2,3-DPG, as well as the concentration of ATP, stayed above
      acceptable values for longer periods than those described with other Optional
      Additive Solutions (OAS). Spontaneous hemolysis was kept below 1%, cell
      morphology, viscosity, deformability and other factors such as pH, the ratio of
      glucose consumption to lactate formation, the total adenylates and energetic
      charge indicate that good properties should be seen after 49 days' storage. In
      vivo survival studies using a double isotope technique showed that at least 75%
      of those RBC stored in this OAS for 49 days were still in circulation 24 hours
      after injection. Therefore RBC stored in PAGGS-S can be kept for 49 days with
      excellent in vivo survival, as well as maintaining DPG levels for up to 3 weeks.
      Furthermore, a clinical trial in routine conditions for use has been carried out
      with surgical and medical patients as well as with hemodialysed patients. The
      results obtained are those that could at least be expected of normal stored
      blood. As regards RBC/PAGGS-Sorbitol, it would be reasonable to propose a storage
      period of 49 days in the liquid state.

PMID- 7503512
TI  - [Strategy of quality of the application of the Huriet law in hospitals].
AB  - Due to the "Huriet" law, the hospital pharmacist has new responsibilities in
      biomedical research. This article reports the activities of Pitie-Salpetriere
      hospital. We also expose the organisation of drug dispensation and storage in our
      hospital pharmacy.

PMID- 7503513
TI  - Lasting success in teenage reduction mammaplasty.
AB  - Symptomatic relief of macromastia following reduction mammaplasty in the adult
      female population is well documented. Teenagers undergoing breast reduction may
      be at risk for recurrent symptoms secondary to postoperative breast development.
      The psychological consequences of prominent scars, sensory loss, and inability to
      breastfeed may overshadow the early symptomatic relief gained from reduction
      mammaplasty. Eighty-six patients who had undergone bilateral reduction
      mammaplasty prior to 20 years of age from 1970 to 1990 were identified from
      hospital and office charts. Forty-eight patients (56%) were successfully
      contacted and completed a detailed questionnaire evaluating preoperative,
      postoperative, and present symptoms as well as physical and psychological
      consequences of their surgery. Patient age ranged from 15.0 to 19.9 years with a
      mean of 17.8 years. Average length of follow-up time was 5.9 years, ranging from
      1.4 to 20.4 years. Sustained relief of symptoms in those patients with
      preoperative back pain, neck pain, shoulder strap pain, and submammary rash
      occurred in 76%, 78%, 89%, and 93%, respectively, despite the fact that 72%
      reported at least some regrowth of breast tissue. Seventy-three percent reported
      being happy with their current breast size, 94% would have the procedure now if
      they had not had the surgery as teenagers, and 94% would recommend breast
      reduction to a friend with macromastia. Teenage patients who undergo reduction
      mammaplasty do not suffer from marked return of symptoms, and long-term
      satisfaction remains high.

PMID- 7503514
TI  - Long-term experience with nipple-areola tattooing.
AB  - Although nipple-areola tattooing is now a well-accepted step in breast
      reconstruction, little is known about its long-term effectiveness. A
      retrospective study of our 6-year experience in tattooing 151 patients was thus
      carried out. Patients were surveyed regarding color match, satisfaction, and
      complications. Follow-up ranged from 1 to 75 months (mean, 25.2 months). Fifty
      seven percent of respondents said their tattoo looked similar to the normal
      areola. There were five (3%) infections, one rash, and one slough. Ten percent of
      tattoos needed a touch-up later to correct for excessive fading. Nearly 60% of
      tattoos were ultimately lighter than the normal. Eighty-four percent of the
      tattoos were rated as satisfactory, and 86% of the patients said they would
      repeat the procedure if given the same choice again. Nipple-areola tattooing done
      with iron oxide and titanium dioxide pigments thus appears to be a reasonably
      safe and effective procedure in most patients but may require one or more
      subsequent touch-ups for appropriate color match.

PMID- 7503515
TI  - The inframammary ligament: myth or reality?
AB  - After histological investigation, we concluded that a transversely oriented
      inframammary ligament extending from the sternum to the lateral margin of the
      pectoralis major muscle is invariably present in female transsexuals. The
      literature on this subject is reviewed.

PMID- 7503516
TI  - Effect of syringe-assisted liposuction on activation of cascade systems and
      circulating cells when using the superwet or tumescent technique.
AB  - Although liposuction is considered to be a relatively safe procedure, several
      deaths and nonfatal serious complications such as sepsis, toxic shock syndrome,
      thromboembolic disease, fat emboli, and adult respiratory distress syndrome have
      been reported. In the present study, we have investigated a wide variety of
      components belonging to the coagulation, fibrinolytic, plasma kallikrein-kinin,
      and complement systems in 22 patients undergoing syringe-assisted liposuction
      using the superwet or tumescent technique. In spite of a relatively high mean
      aspirate volume (2,648 ml), only small changes over time well within the normal
      range were found for the different parameters. In nine randomly selected
      patients, we also measured interleukin 6 and tumor necrosis factor-alpha. The
      size of the interleukin-6 peaks was found to be of the same order of magnitude as
      those measured in patients undergoing hernia repair or percutaneous
      cholecystectomy but lower than those in patients undergoing open cholecystectomy,
      breast reduction, or breast reconstruction. Tumor necrosis factor-alpha was not
      detected in any sample in any of the patients. We conclude that syringe-assisted
      liposuction with the present aspirate volumes using the superwet or tumescent
      technique represents a small to moderate surgical trauma without clinical
      significant activation of the cascade systems.

PMID- 7503517
TI  - Harvest of sural nerve grafts using the endoscope.
AB  - Endoscopic surgical techniques were employed in 5 patients to harvest the sural
      nerve atraumatically with a minimal number of skin incisions. The medial sural
      nerve was harvested by two 2-cm-wide transverse incisions made under endoscopic
      magnified visualization, which allowed the surgeon to see the detailed structure
      of the nerve and surrounding tissue. This method requires minimal traction of the
      nerve during nerve dissection, and postoperative pain and swelling were less than
      encountered with conventional methods, because the method we have employed is
      less invasive and atraumatic.

PMID- 7503518
TI  - Plastic and reconstructive surgery in epidermolysis bullosa: clinical experience
      with 110 procedures in 25 patients.
AB  - We present clinical experience with 110 reconstructive procedures in 25 patients
      with epidermolysis bullosa, a group of rare heritable disorders characterized by
      marked fragility of the skin and mucosa. We discuss management of hand and foot
      deformities unique to epidermolysis bullosa patients, excision of squamous cell
      carcinoma, and reconstruction of oral, nasal, and ocular tissues. All patients
      underwent these procedures without major surgical or anesthetic complications. We
      analyze surgical outcome and formulate guidelines to avoid damaging the skin and
      mucosa.

PMID- 7503519
TI  - Medial canthopexy: an experimental and biomechanical study.
AB  - Medial canthopexy is associated with a significant failure rate. A cadaveric
      study was undertaken to evaluate the biomechanics of the medial canthal tendon
      and three types of fixation devices for medial canthopexy. Eight medial canthal
      tendons were assessed in 4 fresh-frozen cadaver heads. The medial canthal tendon
      was found to be much stronger than previously suspected, with an average breaking
      strength of 36 newtons and an elongation of 6.25 mm. The tendon-bone complex was
      noted to be closely matched biomechanically. Three medial canthopexy techniques
      were then assessed: transnasal wire over a button, 1.7-mm screw fixation into the
      medial orbit, and the Mitek GII anchor. Their respective holding strengths were
      74%, 92%, and 97% of that of the contralateral intact medial canthal tendon. The
      three types of fixation devices all provided excellent ultimate biomechanical
      strength.

PMID- 7503520
TI  - Vein, silastic, and polyglycolic acid fine mesh: a comparative study in
      peripheral nerve repair.
AB  - We investigated three sheathing materials (autogenous vein, silastic, and
      polyglycolic acid fine mesh) using the rat model. Forty rats were divided into
      five groups of eight animals each. Group A animals underwent transection of the
      sciatic nerve but had no repair. In Group B, a standard epineural repair was
      performed. In Groups C, D, and E, the nerve was repaired as in Group B with the
      addition of autogenous vein, Silastic, and polyglycolic acid fine mesh sheaths,
      respectively. Nerve regeneration and function were assessed using sciatic
      functional index, nerve conduction studies, and light microscopy. Sheathing
      methods showed no statistically significant advantage to standard epineural
      repair without a sheath.

PMID- 7503521
TI  - Decision making in primary surgical repair of myelomeningoceles.
AB  - A 5-year review of 43 consecutive patients presenting to Scottish Rite Children's
      Medical Center with an open myelomeningocele defect was undertaken. The aim of
      the present study was to analyze the myelomeningocele defects, dimensions, and
      area to better define those factors that dictate the need for plastic surgical
      consultation for wound closure. Of the 43 patients identified, two were excluded
      because they first presented as older children; the remaining 41 all had their
      myelomeningoceles repaired within the first 36 hours of life. Of these, 31
      underwent repair by the Neurosurgical Service, whereas for 10 patients (24.4%),
      the Plastic Surgery Service was asked to assist with closure. Comparison showed
      the mean (+/- standard deviation) area in the referred patients was 27.4 (7.6)
      cm2 versus 17.6 (7.9) cm2 in the patients not referred for closure (p = 0.002). A
      trend analysis predicting referral as a function of myelomeningocele area showed
      that 0 of 10 (0%) with an area of less than 15 cm2, 2 of 13 (15.4%) with an area
      equal to 15 to 20 cm2, 3 of 7 (42.9%) with an area of 21 to 25 cm2, and 4 of 9
      (44%) with an area greater than 25 cm2 were referred (p = 0.001). Data from the
      interpretation of maximum myelomeningocele dimension also showed statistically
      significant trends in referral. Using multiple logistic regression, it was found
      that the odds of referral increased by a factor of 3.3 for every 1 cm increase in
      maximum dimension.

PMID- 7503522
TI  - Refinements of pre-, intra-, and postoperative care to prevent complications of
      vaginoplasty in male transsexuals.
AB  - In the period of 1980 to 1992, primary genital reassignment surgery was performed
      for 200 male-to-female transsexuals aged 18 to 71 years. For this, the penile and
      scrotal skin inversion technique was used. Because, apart from minor
      complications in 32 patients, neovaginal obliteration was encountered only twice
      and early in this series, we believe it is worthwhile to report in detail our pre
      , intra-, and postoperative measures. Discontinuation of hormonal treatment may
      prevent venous thrombosis. The preoperative rectal rinse and antibiotics are
      believed to be of importance to avoid rectovaginal fistulae. A soft and pliable
      intravaginal Vaseline tampon may prevent sloughing of the inverted skin.
      Intermittent daily neovaginal dilatation may successfully ensure neovaginal depth
      and width and, in our opinion, is superior to a long-term continuous intravaginal
      stent.

PMID- 7503523
TI  - Reducing ischemia-reperfusion injury in rat island groin flaps using
      dexamethasone.
AB  - Reducing reperfusion injury is effective in reducing flap loss after prolonged
      ischemia. Anti-inflammatory therapy reduces reperfusion injury in canine cardiac
      muscle and ex vivo rat cremaster muscle; however, to date, there are no studies
      involving the use of anti-inflammatory agents in ischemic skin flaps. This study
      was designed to assess the effects of dexamethasone and indomethacin on the
      viability of rat island groin flaps subjected to 10 hours of ischemia. The
      ischemic control and the treatment group flaps were subjected to 10 hours of
      ischemia by clamping the inferior epigastric vascular pedicle. The treatment
      groups received either intravenous dexamethasone or intravenous indomethacin
      after the flap vascular pedicles were clamped. Our results showed significant
      improvement (p < 0.05, Fisher's exact test) in ischemic flap survival using
      dexamethasone. The specific mode of action of dexamethasone was not investigated;
      however, its anti-inflammatory effects were most likely responsible for the
      improvement of flap survival by suppressing the circulating neutrophil and
      decreasing reperfusion injury. Dexamethasone is easily available for clinical
      use, and its use should be considered in cases of prolonged ischemia in skin
      flaps.

PMID- 7503524
TI  - Fibroblast responses to cytokines are maintained during aging.
AB  - Impaired wound healing in older individuals may result from a global deficit of
      fibroblast activity or a decreased response of aged fibroblasts to stimulation by
      inflammatory cytokines. Twenty-eight fibroblast cell strains were developed from
      normal human skin aged 3 days to 84 years. Mitogenic response to cytokines,
      epidermal growth factor, tumor necrosis factor-alpha, platelet-derived growth
      factor or fetal bovine serum was determined using a 4-hour 3H-thymidine
      incorporation assay. Synthesis of collagen and noncollagen proteins was
      determined basally and in response to transforming growth factor-beta using a 6
      hour 3H-proline incorporation assay. Neither the mitogenic response to cytokine
      stimulation (p > 0.3) nor the synthesis of collagen and noncollagen protein after
      transforming growth factor-beta stimulation (p > 0.4) varied with the age of the
      cell donor. Individual cell lines' response to cytokine stimulation varied
      widely, reflecting differences commonly seen in patients' wound-healing
      abilities. Cellular responses to wound-healing cytokines are preserved as people
      age. Abnormalities in wound healing in older patients may be the result of
      altered immune initiation of healing or the cumulative result of concomitant
      disease.

PMID- 7503525
TI  - Amputation neuromas of the great auricular nerve after rhytidectomy.
AB  - A 56-year-old woman presented with complaints of a tender nodule in the anterior
      triangle of her left neck. The nodule, which was easily palpable through the
      skin, was approximately 1 x 1.5 cm in size and was, at first, thought to be a
      lymph node. At operation, a large neuroma of the distal terminus of the
      transected great auricular nerve was found. Significantly, the patient had
      undergone a full rhytidectomy some 9 years previously, and it appears that the
      neuroma was a consequence of iatrogenic injury to the nerve at that time.

PMID- 7503526
TI  - Successful use of leeches in the treatment of purpura fulminans.
AB  - A case of purpura fulminans secondary to pneumococcal septicemia is presented in
      an 8-month-old girl. The purpuric lesions on the fingers of both hands, as well
      as on the lower extremities, were treated by the local application of medicinal
      leeches. There was nearly complete salvage of the threatened tissues and the baby
      made a complete recovery. The possible mechanisms by which the leeches may have
      contributed to the clinical salvage are discussed.

PMID- 7503527
TI  - Infiltrating lipoma of the face.
AB  - Lipomas are the most common soft-tissue tumor in humans, accounting for almost
      half of all soft-tissue tumors removed for any reason. Typically, these tumors
      are well circumscribed, are easy to remove, present few difficulties in
      diagnosis, and rarely recur. For this reason, they have often been regarded as
      insignificant. We present a case of infiltrating lipoma of the face that is
      unusual both for its diagnosis as well as its location.

PMID- 7503528
TI  - Limb salvage with microvascular free flap reconstruction using simultaneous
      polytetrafluoroethylene graft for inflow.
AB  - Microvascular free flaps have been successfully used to cover defects of the
      lower extremity. In patients with peripheral vascular disease and lower extremity
      defects, revascularization with in situ or reversed saphenous vein bypass graft
      combined with microvascular tissue transfer can salvage a limb that would
      otherwise be amputated. However, some of these patients may not have autologous
      vein available for the bypass procedure. We present a case of a 69-year-old man
      who underwent revascularization with a long polytetrafluoroethylene (PTFE) graft
      and a simultaneous microvascular free flap reconstruction using the PTFE graft as
      the inflow. The patient had undergone coronary artery bypass graft with saphenous
      vein and experienced a nonhealing wound of the distal saphenous vein harvest site
      and exposure of 8 cm of tibia. Angiogram revealed a significant stenosis of the
      common iliac artery, occluded superficial femoral artery, faint filling of the
      profunda femoris artery, and a faintly reconstituted posterior tibial artery.
      Because the patient had no available saphenous vein for bypass, he underwent an
      axillary-profunda and profunda-posterior tibial artery bypass with PTFE. A rectus
      abdominus microvascular free flap with direct anastomosis of the inferior
      epigastric artery to the PTFE was used to cover the exposed bone. The patient
      currently ambulates without difficulty. Limb salvage using bypass with PTFE
      combined with simultaneous microvascular free flap reconstruction is possible in
      selected patients.

PMID- 7503529
TI  - Amniotic band attachment to a fetal limb: demonstration with real-time
      sonography.
AB  - On ultrasonography, an 18-week-old fetus was found to have his left hand attached
      to an amniotic band. The child was born with typical anomalies of the amniotic
      band syndrome. This observation tends to support an extrinsic theory for the
      pathogenesis of the amniotic band syndrome.

PMID- 7503530
TI  - Use of groin flap and anterolateral thigh adipofascial flap of tensor fascia lata
      for reconstruction of a wide lower abdominal wall defect.

PMID- 7503531
TI  - Correction of constricted ear.
AB  - We present a case of moderate constricted ear corrected using a modified Tanzer's
      technique for the helical deformity and lengthening the lower third of the pinna
      with a cutaneous transposition flap from the retroauricular area. The operation
      begins with a rapid intraoperative expansion of the retroauricular skin. Then an
      incision is made on the posteromedial ear aspect and the ear is degloved using a
      subperichondral plane. The upper pole of the cartilage is expanded and rearranged
      by an anteriorly pedicled helical flap and a cartilaginous graft is taken from
      the constricted part of the concha. The lower third of the pinna is lengthened by
      a cutaneous transposition flap from the retroauricular area. Thus, the ear is
      lengthened and the skin that otherwise tends to maintain its "constricted" form
      relapses. A second surgical stage is performed, under local anesthesia, to cut
      the pedicle of the retroauricular transposition flap. This method consents an
      adequate correction of the shape and an effective expansion, of about 1 cm, in
      the length of the pinna.

PMID- 7503532
TI  - Facial plaque-type blue nevus and its reconstruction.
AB  - Blue nevi rarely appear in a plaque form. Because of their rarity and unusual
      clinical appearance, these nevi may present a diagnostic problem. We described a
      large plaque-type blue nevus measuring about 9 x 6 cm on the right cheek of a 22
      year-old man. It was characterized by several dark-blue macules and papules with
      intervening areas of faint blue discoloration. Excision of this unusual plaque
      type blue nevus with reconstruction using tissue expander was performed
      successfully. A 6-year postoperative follow-up revealed satisfactory results.

PMID- 7503533
TI  - Subungual exostosis of the finger.
AB  - Subungual exostosis is a benign tumor or cartilaginous bone beneath or adjacent
      to the nail. It is usually a solitary lesion that develops most often in the
      substance of the great toe and less frequently in other toes. It rarely occurs in
      the fingers. We present a case of subungual exostosis of the finger. At 4-year
      follow-up, the result was excellent, with no sign of recurrence.

PMID- 7503534
TI  - American Plastic Surgery and the World.

PMID- 7503535
TI  - Re: Analysis of explanted silicone implants: a report of 300 patients.

PMID- 7503536
TI  - Re: Invited discussion of tissue expansion-assisted prefabrication of the
      forehead flap for nasal reconstruction.

PMID- 7503537
TI  - [Eosinophilic granuloma of bones in children].
AB  - Eosinophilic granuloma of bone or Langerhans cell histiocytosis is mostly
      unifocal. It appears on plain X Ray as a solitary destructive lesion of long
      bones or flat bones. CT is useful to define the extension to the cortical bone
      and also to precisely localize the lesion when the anatomy is complex (hip,
      spine, base of the skull). MR is very useful in case of more aggressive lesions
      when there is extension to soft tissues. Differential diagnosis includes
      circumscribed osteitis and tumors in the case of extensive destruction. The
      natural course of solitary lesions is favorable, spontaneously or with therapy.
      The prognosis is more serious in the case of multiple lesions.

PMID- 7503538
TI  - [Craniofacial bone abnormalities in von Recklinghausen neurofibromatosis].
AB  - Cases of cranio-facial bone anomalies were observed in 40 cases of
      neurofibromatosis. The cranio-facial skeletal manifestations are numerous and
      varied. Radiographic investigation is important to confirm the diagnosis, when
      neurologic and cutaneous signs are absent. The diagnosis should be easily
      confirmed by a conventional radiographic study.

PMID- 7503540
TI  - Musculoskeletal amyloid disease: MRI features.
AB  - A case of arthropathy and soft tissue masses due to amyloid deposition in a
      patient with myeloma is reported. The radiologic and magnetic resonance findings
      of musculoskeletal amyloidosis are described. The amyloid masses show
      heterogeneous signal intensity, with a signal lower than muscle and intermingled
      areas of marked hyperintensity on T2-weighted images.

PMID- 7503539
TI  - [Demonstration of a communication between the ankle joint and the subchondral
      synovial cyst of the tibial medial malleolus. Contribution of noninvasive
      imaging].
AB  - The authors report a case of an intraosseous cyst located in the distal end of
      the tibia. A typical subchondral defect with a narrow opening in the ankle joint
      was well defined by CT scan and MRI. The diagnostic value of noninvasive
      techniques and differential diagnosis are specified after a review of the
      literature.

PMID- 7503541
TI  - [Bilateral adrenal hemorrhage induced by stress. Radiological diagnosis. Apropos
      of a case].
AB  - Bilateral hemorrhage of the adrenal gland is a rare disease in adults. Although
      stress is often said to be the cause, it is rarely observed. The non specific
      clinical manifestations, and the absence of adrenal insufficiency demonstrate the
      importance of radiology. The diagnosis is made by ultrasonography and CT scan,
      which reveals an oval adrenal mass of high density that subsequently decreases in
      both size and density.

PMID- 7503542
TI  - Phosphorylation of wheat germ initiation factor 2 (eIF-2) by N-ethylmaleimide
      treated wheat germ lysates and by purified casein kinase II does not affect the
      guanine nucleotide exchange on eIF-2.
AB  - Phosphorylation of the small subunit of eukaryotic initiation factor-2 (eIF-2
      alpha) impairs protein synthesis in mammalian systems. It is not known, however,
      if a similar regulatory mechanism exists in plants. Previous reports indicate
      that one of the wheat germ eIF-2 subunits, the p40-41 doublet, is phosphorylated
      by heterologous eIF-2 alpha kinases. Here we report that phosphorylation of the
      small subunit in wheat germ eIF-2, p36, occurs in translating wheat germ lysates
      which are pretreated with N-ethylmaleimide (NEM) and dithiothreitol. Also, a
      purified sea star casein kinase II (CKII) phosphorylates the p41-42 doublet and
      p36 subunits of wheat germ eIF-2. While heme-regulated eIF-2 alpha kinase from
      reticulocyte lysates does not inhibit wheat germ protein synthesis, CKII and NEM
      are found to be inhibitory. To determine whether phosphorylation of the small
      subunit (p36) is the cause for protein synthesis inhibition, we have further
      studied the exchange of labeled GDP for unlabeled GDP in the preformed eIF-2.
      [3H]GDP complex in vitro in the presence of CKII and ATP. The GDP exchange in eIF
      2.GDP complex can occur without the addition of any protein factor and the
      exchange reaction is marginally inhibited by CKII. A 0-70% ammonium sulfate cut
      fraction, prepared from NEM-treated wheat germ lysate, also does not inhibit the
      guanine nucleotide exchange reaction. These findings suggest that the protein
      synthesis inhibition in these cases is not mediated by eIF-2 phosphorylation.

PMID- 7503543
TI  - Age-related shortening of poly(A) tail of albumin mRNA.
AB  - To determine the molecular mechanisms of age-related changes in hepatic albumin
      gene expression, male Fisher 344 rats at 4, 12, and 24 months of age were
      studied. The hepatic albumin content was modestly increased by 20% and plasma
      albumin concentration was not altered with age. There were no age-related changes
      in albumin mRNA content of the liver. The in vivo synthetic rate of albumin as
      measured with [14C]-leucin incorporation in 4-month-old rats (350 +/- 24.5 cpm)
      was not significantly different from that in 24-month-old rats (393 +/- 30.3
      cpm). However, in vitro translational efficiency of albumin mRNA from 24-month
      old rats was only 49% of that in 4-month-old rats. This was correlated with
      shortening of the poly(A) tail of albumin mRNA from approximately 300-450 bases
      in 4-month-old rats to only 50-100 bases in 24-month-old rats. The reduced
      albumin mRNA translational efficiency in vitro along with shortening of the
      poly(A) tail with age is probably an adaptive response since hepatic albumin
      content was increased and plasma albumin concentrations were not altered with
      age. The age-related shortening of the poly(A) tail is yet another mechanism of
      age-related alterations in the expression of specific genes where the changes
      seen with age are mostly translational.

PMID- 7503544
TI  - Effects of glutathione on Fenton reagent-dependent radical production and DNA
      oxidation.
AB  - The effects of glutathione (GSH) on the generation of radicals and the oxidation
      of DNA by Fenton reagent were studied. Hydroxyl radicals and thiyl radicals were
      detected by electron spin resonance spin trapping when GSH-Fe(II) reacted with
      H2O2; however, the mixture was ineffective at promoting the hydroxylation of 2'
      deoxyguanosine in calf thymus DNA. When the concentrations of ferrous iron and
      hydrogen peroxide were both 100 microM, the concentration of GSH required to
      inhibit 8-hydroxy-2'-deoxyguanosine (8-OHdG) production by 92% was 1 mM. Other
      thiol compounds were also effective at inhibiting 8-OHdG formation; however,
      mannitol and benzoate were ineffective at inhibiting 8-OHdG formation when
      present at the same concentration. Single strand breaks were detected in phi X174
      plasmid DNA treated with 2 microM Fe(II) and 2 microM H2O2; furthermore, the
      addition of 50 microM GSH to this system inhibited single strand break formation
      by 95%. In conclusion, GSH protected DNA from oxidation by Fe(II) and H2O2 even
      though it did not completely inhibit the production of radicals by the Fenton
      reaction.

PMID- 7503545
TI  - Antioxidant activity of reduced plastoquinone in chloroplast thylakoid membranes.
AB  - The antioxidant effect of reduced plastoquinone was studied in chloroplast
      membranes. Isolated spinach thylakoid membranes were subjected to strong
      illumination followed by analysis of pigment bleaching and lipid peroxidation.
      The plastoquinone pool was kept in the reduced or oxidized state during the light
      stress by the addition of the electron transport inhibitors 2,5-dibromo-3-methyl
      6-isopropyl-p-benzoquinone and o-phenanthroline, respectively. In the absence of
      inhibitors there occurred a bleaching of carotenoids and chlorophyll a, while
      chlorophyll b was unchanged. Formation of thiobarbituric acid reactive
      substances, used as a measure of lipid peroxidation, was negligible during the
      first hour of strong illumination, but during the second hour there was a marked
      increase in the rate of lipid peroxidation. Reduction of the plastoquinone pool
      resulted in a virtually complete inhibition of lipid peroxidation and pigment
      bleaching. In contrast, conditions of an oxidized plastoquinone pool markedly
      enhanced lipid peroxidation and pigment bleaching. It is argued that the reduced
      form of plastoquinone can act as a scavenger of toxic oxygen species generated in
      the thylakoid membranes during strong illumination.

PMID- 7503546
TI  - Mycobacterial DNA gyrase: enzyme purification and characterization of
      supercoiling activity.
AB  - Putative structural genes encoding Mycobacterium bovis BCG gyrase A and gyrase B
      subunits were expressed in Escherichia coli under the control of a regulated
      promoter. Upon induction, high levels of proteins of M(r) 92,000 and 75,000 were
      generated. Purification and reconstitution of these proteins yielded an enzyme
      with bacterial DNA gyrase activity. DNA supercoiling activity of the
      mycobacterial enzyme required ATP, Mg2+, and spermidine. Like other bacterial DNA
      gyrases, the supercoiling activity of the mycobacterial enzyme was inhibited by
      low concentration of the classical gyrase B subunit inhibitors novobiocin and
      coumermycin. Older gyrase A subunit inhibitors, nalidixic and oxolinic acid, had
      no effect on the supercoiling activity at 400 to 800 micrograms/ml. However, in
      vitro assays to show the inhibition of supercoiling activity and stimulation of
      cleavable complex formation demonstrated that ciprofloxacin is a potent inhibitor
      of mycobacterial DNA gyrase. The availability of highly purified mycobacterial
      DNA gyrase could aid in future investigations of quinolone derivatives targeting
      Mycobacterium specifically.

PMID- 7503548
TI  - Separation and quantitation of cytochrome c oxidase subunits by Mono-Q fast
      protein liquid chromatography and C18 reverse-phase high-performance liquid
      chromatography.
AB  - Mono-Q fast protein liquid chromatography (FPLC) combined with C18 reverse-phase
      HPLC was used for quantitative subunit analysis of bovine heart cytochrome c
      oxidase, a multisubunit membrane complex. By this approach normal cytochrome c
      oxidase preparations were shown to be a mixture of enzyme that has all 13
      subunits and complexes that are missing 1-3 subunits. A distinct advantage of
      this procedure is that homogeneous 13- or 11-subunit enzyme can be easily
      isolated from heterogeneous cytochrome c oxidase mixtures. The method involves:
      (1) separation of complexes that are depleted of subunits using Mono-Q FPLC and
      (2) quantitative subunit analysis of the purified complexes by C18 reverse-phase
      HPLC with a water/acetonitrile gradient in 0.1% trifluoroacetic acid. The
      approach has four distinct advantages over other methods of analysis, e.g.,
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) or C4
      reverse-phase HPLC. (1) The reproducible yield and the baseline resolution
      between each eluting subunit permits quantitative determination of the subunit
      content with an accuracy of +/- 5%. (2) Subunits that are very difficult to
      separate by SDS-PAGE, e.g., subunits VIa, VIb, and VIc, are completely resolved
      by this system. (3) The combination of Mono-Q purification and C18 reverse-phase
      HPLC analysis permits an accurate assessment of both homogeneity and subunit
      content. (4) The quantitative nature of the reverse-phase HPLC system also makes
      it a powerful method for analyzing the specificity and extent of chemical
      modification of specific subunits as is shown by the difference in reactivity of
      subunit VIa toward N-iodoacetylamidoethyl-1-aminonaphthalene-5-sulfonate and 4,4'
      dipyridyl disulfide.

PMID- 7503547
TI  - Calcium indirectly increases the control exerted by the adenine nucleotide
      translocator over 2-oxoglutarate oxidation in rat heart mitochondria.
AB  - The effect of calcium on the control exerted by the adenine nucleotide
      translocator over respiration in isolated heart mitochondria was investigated in
      order to determine whether calcium directly stimulates the translocator. At
      respiration rates intermediate between states 3 and 4, Ca2+ is shown to increase
      the control over 2-oxoglutarate oxidation exerted by the adenine nucleotide
      translocator in rat heart mitochondria. This did not occur when succinate was the
      respiratory substrate, even though the control exerted by the translocator was
      substantial, indicating that Ca2+ does not have a direct effect on the adenine
      nucleotide translocator. Ca2+ increased the uncoupled oxidation rate of 2
      oxoglutarate, but not succinate. Using the summation theorem for flux control,
      the effect of Ca2+ is explained by a shift of the control over respiration rate
      toward the adenine nucleotide translocator, from the respiratory chain,
      presumably as the result of the activation of the 2-oxoglutarate dehydrogenase
      complex.

PMID- 7503549
TI  - Inactivation of human immunodeficiency virus type 1 reverse transcriptase by
      oltipraz: evidence for the formation of a stable adduct.
AB  - Oltipraz (5-pyrazinyl-4-methyl-1,2-dithiole-3-thione), which is undergoing
      clinical evaluation as an anticarcinogen, also inhibits HIV-1 replication (IC50
      approximately equal to 10 microM). The inactivation of RT appears to be a
      relevant antiviral mechanism since oltipraz blocks viral replication in acutely
      infected T-cell lines, but is ineffective in chronically infected ACH-2 cells (H.
      J. Prochaska, W. G. Bornmann, P. Baron, and B. Polsky (1995) Mol. Pharmacol. 48,
      15-20). Since a nucleophilic amino acid is a likely target for oltipraz, we
      assessed whether the conserved cysteine residues of HIV-1 RT (38Cys or 280Cys)
      were the target(s) for oltipraz, and we synthesized [Me 14C]oltipraz to determine
      if oltipraz forms a stable adduct with RT. Thus, HIV-2 RT as well as wild-type,
      38Cys-->Ser, 280Cys-->Ser, and the Cys-->Ser double mutant of HIV-1 RT were
      purified from the lysates of transformed Escherichia coli strain DH5 alpha (A.
      Hizi, M. Shaharabany, R. Tal, and S. H. Hughes (1992) J. Biol. Chem. 267, 1293
      1297) via a purification procedure that included (NH4)2SO4 fractionation followed
      by gel filtration, dye-ligand, and ion-exchange chromatographies. Procion yellow
      H4R was chosen as the dye-ligand chromatography since it was the most potent and
      selective inhibitor of RT among seventy reactive dyes that were screened. Mono Q
      anion-exchange chromatography with diethanolamine (pH 9) resulted in the
      generation of heterodimeric RT from a predominantly homodimeric enzyme
      preparation. Because the instability of dilute RT preparations at room
      temperature rendered the kinetic evaluation of inactivation difficult, we sought
      to identify conditions that prevent denaturation of these enzymes. High
      concentrations (25 mM) of MgCl2 had a stabilizing effect. Oltipraz behaved
      kinetically as an irreversible inhibitor of all RTs purified, and the kinetic
      constants for the inactivation of these enzymes were not significantly different
      from wild-type HIV-1 RT (Ki = 17.0 +/- 4.1 microM; k3 = 0.214 +/- 0.051 h-1). In
      stark contrast, oltipraz neither inhibited nor inactivated the Klenow fragment of
      DNA polymerase I, whose subdomain structure is similar to the p66 subunit of RT.
      Wild-type RT was incubated with 60 microM [Me 14C]oltipraz for 4 h and was then
      subjected to gel filtration chromatography. The [14C] label comigrated with RT
      with a stoichiometry of binding of 0.88 +/- 0.05 oltipraz per inactivated RT
      subunit (N = 3 experiments), and the [14C] label remained bound after treatment
      with 4 M urea.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7503550
TI  - Nitric oxide inhibition of lipoxygenase-dependent liposome and low-density
      lipoprotein oxidation: termination of radical chain propagation reactions and
      formation of nitrogen-containing oxidized lipid derivatives.
AB  - Lipoxygenase-induced lipid oxidation contributes to plasma lipoprotein oxidation
      and may be an underlying pathogenic mechanism of atherogenesis. Since
      inactivation of the vasorelaxant actions of nitric oxide (.NO) plays a critical
      role in the impaired function of atherosclerotic vessels and because .NO reacts
      rapidly with other radical species, we assessed the influence of .NO on
      lipoxygenase-catalyzed oxidation of linoleic and linolenic acid, 1-palmitoyl-2
      arachidonyl-sn-glycero-3-phosphocholine (PC) liposomes, hypercholesterolemic
      rabbit beta-very-low-density lipoprotein, and human low-density lipoprotein.
      Soybean lipoxygenase (SLO)-induced lipid oxidation was assessed by accumulation
      of conjugated dienes, formation of lipid hydroperoxides, oxygen consumption, and
      liquid chromatography-mass spectrometry. Different rates of delivery of .NO to
      lipid oxidation systems were accomplished either by infusion of .NO gas
      equilibrated with anaerobic buffer or via .NO released from S-nitrosoglutathione.
      Nitric oxide alone did not induce lipid peroxidation, while exposure to SLO
      yielded significant oxidation of fatty acids, PC liposomes, or lipoproteins in a
      metal ion-independent mechanism. Low concentrations of .NO, which did not
      significantly inhibit the activity of the iron-containing lipoxygenase, induced
      potent inhibition of lipid peroxidation in a dose-dependent manner. Mass spectral
      analysis of oxidation products showed formation of nitrito-, nitro-,
      nitrosoperoxo-, and/or nitrated lipid oxidation adducts, demonstrating that .NO
      serves as a potent terminator of radical chain propagation reactions. The
      formation of Schiff's base fluorescent conjugates between SLO-oxidized linoleic
      or linolenic acid and bovine serum albumin (BSA) was also inhibited by .NO via
      reaction with lipid hydroperoxyl radicals (LOO.), thus preventing the reaction of
      LOO. with polypeptide amino groups. Mass spectrometry analysis showed that both
      lipid peroxidation products and nitrogen-containing oxidized lipid species
      decreased in the presence of BSA. We conclude that .NO can play a potent oxidant
      protective role in the vessel wall by inhibiting lipoxygenase-dependent lipid and
      lipoprotein oxidation. This occurs via termination of lipid radical chain
      propagation reactions catalyzed by alkoxyl (LO.) and LOO. intermediates of lipid
      peroxidation rather than by inhibition of lipoxygenase-catalyzed initiation
      reactions.

PMID- 7503551
TI  - Mutagenesis and reversion analysis of residue Met-209 of the beta-subunit of
      Escherichia coli ATP synthase.
AB  - Residue beta-Met-209 is conserved in all known F1-ATPase sequences, and the
      mutation beta M209I in Escherichia coli causes profound inhibition of ATP
      synthesis and hydrolysis. Based on the properties of this mutant it had
      previously been proposed that residue beta-209 lies close to the site of
      catalysis. Two approaches were used to study this residue further. First,
      revertants were sought. Only wild-type and beta-Ser-209 were found; the Ser
      revertants involved a two-base change. Significantly, Ser is found at the
      equivalent position in the homologous vacuolar and archaebacterial ATPases.
      Second, all 20 natural amino acids were placed at position beta-209 by
      mutagenesis, and catalytic properties of the mutants were analyzed. The results
      showed that only a limited set of residues supported significant growth or ATPase
      activity, and that many of the mutations impacted severely on catalysis. X-ray
      structure analysis of the bovine enzyme has revealed that residue beta-Met-209
      lies only 3.1. A from residue beta-Glu-181, which has been proposed to act as
      catalytic base. The results reported here emphasize that, in this discrete region
      of the catalytic site, specific stereo-chemical constraints on structure are
      critical for catalysis.

PMID- 7503552
TI  - Insulin-like growth factor-I and its complexes in normal human articular
      cartilage: studies of partition and diffusion.
AB  - Insulin-like growth factor-I (IGF-I) plays a major role in cartilage homeostasis.
      Our objective was to study the penetration of IGF-I, both alone and bound to
      serum proteins, into the different zones of normal human cartilage using
      radioactively labeled IGF-I. The uptake of free IGF-I was higher than that
      predicted on the basis of excluded volume calculations and showed concentration
      dependence: we attributed this to reversible binding of the hormone to the
      tissue. Since the extent of binding was much higher than that calculated for
      binding to cell receptors, we concluded that IGF-I binds to matrix components.
      The kinetics of desorption of IGF-I from cartilage confirmed our conclusions
      regarding binding. The degree of uptake of IGF-I protein complexes prepared by
      labeling human serum with [125I]IGF-I showed that such complexes are largely
      excluded from normal cartilage and that the amounts present in the tissue are too
      low to affect proteoglycan metabolism.

PMID- 7503553
TI  - Concentration and size distribution of insulin-like growth factor-I in human
      normal and osteoarthritic synovial fluid and cartilage.
AB  - The concentration of free insulin-like growth Factor-I (IGF-I) and its complexes
      was determined in human normal and osteoarthritic synovial fluids, using
      ultrafiltration through 20- and 100-kDa membranes, followed by a radioimmunoassay
      of each fraction. In addition, freshly obtained samples of normal and
      osteoarthritic cartilage were incubated for several days, at both 4 and 37
      degrees C. The incubation media (desorbates) were analyzed the same way as the
      synovial fluid samples to yield the concentration of IGF-I in cartilage in situ.
      Our findings are (i) Free IGF-I content is extremely low in both human serum and
      synovial fluid and there is no significant difference between the two; (ii) The
      concentration of total IGF-I in normal human synovial fluid is an order of
      magnitude lower than that in serum due mainly to the decrease in the
      concentration of the large complex; (iii) Preliminary results show that the total
      IGF-I in osteoarthritic synovial fluids is twice as high as in normal fluids;
      (iv) In normal human cartilage the levels of IGF-I in all its forms are very low
      and are consistent with the expected exclusion of large molecules by the
      extracellular matrix; (v) By contrast, in osteoarthritic cartilage, the
      concentrations of all forms of IGF-I are high, probably due to increased
      permeability of the matrix and binding; (vi) The levels of IGF-I found in normal
      human cartilage are more than an order of magnitude lower than those which
      stimulate proteoglycan synthesis in human cartilage in culture, while the IGF-I
      levels in osteoarthritic cartilage lie in the range in which stimulation does
      occur.

PMID- 7503554
TI  - Novel sterol transformations promoted by Saccharomyces cerevisiae strain GL7:
      evidence for 9 beta, 19-cyclopropyl to 9(11)-isomerization and for 14
      demethylation to 8(14)-sterols.
AB  - Cultures of Saccharomyces cerevisiae strain GL7 (a sterol auxotroph) were
      incubated with nonradioactive and tritium-labeled cycloartenol, and the sterol
      composition of the cells was examined by chemical (GLC, TLC, HPLC, MS, 1H-NMR,
      and 13C-NMR) and radiotracer techniques. Several novel sterols were isolated from
      the cells including 14 alpha-methyl ergosta-9(11),24(28)-dien-3 beta-ol, 24 beta
      methyl-9 beta,19-cyclopropyl ergost-8(14)-en-3 beta-ol, and 9 beta,19-cyclopropyl
      ergosta-7(8),24(28)-dien-3 beta-ol. GL7 converted [2-3H]cycloartenol to [2
      3H]ergosterol in low yield (1% incorporation), whereas [2-3H]lanosterol was
      converted to [2-3H]ergosterol in high yield (41% incorporation). The degree of
      sterol absorption and transformation by GL7 was dependent on the type and amount
      of sterol(s) in the growth medium. The results demonstrate for the first time
      that yeast may transform 9 beta,19-cyclopropyl sterols to 9(11)-sterols and delta
      5-sterols and that 14-demethylation of sterols may proceed in GL7 to double bond
      formation either in the 8(14)-position or in the 14(15)-position.

PMID- 7503555
TI  - Purification and characterization of prostaglandin H synthase-2 from sheep
      placental cotyledons.
AB  - Recent identification of a second, inducible form of prostaglandin H synthase
      (PGHS-2) led to the hypothesis that constitutively expressed PGHS (PGHS-1) is
      involved in the homeostatic role of eicosanoids, whereas the inducible enzyme is
      responsible for their inflammatory actions. We report here the purification of
      PGHS-2 from near-term sheep placental cotyledons. The PGHS-2 from this tissue was
      purified in multimilligram quantities by a combination of anion-exchange, size
      exclusion, and affinity chromatography. This enzyme is different from ovine
      seminal vesicle PGHS-1 and was characterized as PGHS-2 based on (a)
      chromatographic properties, (b) immunochemical reactivities with isoenzyme
      specific antibodies, (c) amino acid microsequencing, (d) kinetics of reaction
      with arachidonic acid (Km = 2.1 +/- 0.2 microM vs 8.3 +/- 0.2 microM for ovine
      PGHS-1), and (e) different sensitivities for several non-steroidal
      antiinflammatory drugs. Since the first identification of PGHS, ram seminal
      vesicles served as a rich source of the enzyme (PGHS-1). Our studies establish
      the sheep placental cotyledons as a rich natural source of PGHS-2.

PMID- 7503556
TI  - Isolation and characterization of a trypsin from the slipper lobster, Thenus
      orientalis (Lund).
AB  - Trypsin has been isolated and purified from the digestive glands of the slipper
      lobster, Thenus orientalis. It is a glycoprotein with a molecular mass of
      approximately 35 kDa as judged by both SDS-PAGE and gel filtration. The N
      terminal amino acid sequence has strong homology to crustacean trypsins. This is
      confirmed by the cross-reaction of crustacean trypsins with antibodies to the T.
      orientalis enzyme. Despite a 40% identity with the bovine trypsin N-terminal
      sequence, there was no cross-reaction with the mammalian serine proteases. The
      optimum kcat and kcat/Km values for N-alpha-benzoylarginine-p-nitroanalide were
      0.91 s-1 and 9.7 x 10(3) M-1 s-1, respectively, with this specificity constant
      being lower than those reported for other crustacean trypsins. Inhibition studies
      indicated the presence of serine and histidine at the active site and pKa of the
      catalytic histidine residue was found to be 5.7 in the free enzyme and 4.7 in the
      Michaelis complex.

PMID- 7503557
TI  - Induction of nitric oxide synthase and concomitant suppression of superoxide
      dismutases in experimental colitis in rats.
AB  - Reactive oxygen species are thought to play an important role in some bowel
      diseases. In order to evaluate the participation of nitric oxide and superoxide
      in such diseases, we examined the expression of nitric oxide synthase (NOS) and
      superoxide dismutase (SOD) as well as their activities in whole excised colons of
      rats with colitis induced by intralumenal administration of 2,4,6
      trinitrobenzenesulfonic acid. A marked increase in the inducible form of NOS mRNA
      was detected and NOS activity was coincidentally augmented in the group
      administered unbuffered TNBS (pH 1.0), in which severe inflammation was revealed
      by microscopic examination and myeloperoxidase activity of invading neutrophils
      in the tissues. The levels of the Mn- and Cu,Zn-SOD proteins as well as SOD
      activity were suppressed, although expression of the Mn-SOD mRNA was enhanced in
      colitis tissues. The elevation of NOS activity and the suppression of SOD
      activity occurred concomitantly at the stage of severe inflammation. This would
      increase peroxynitrite formation from superoxide and nitric oxide and enhance the
      tissue damage in experimental colitis.

PMID- 7503558
TI  - The effect of detergents on the reduction of tetrazolium salts.
AB  - Detergents, such as Triton X-100, markedly increase the reduction of tetrazolium
      salts by xanthine oxidase plus xanthine, or by NADH. This effect of detergent, in
      the case of the xanthine oxidase catalyzed process, is seen aerobically but not
      anaerobically. Increasing the rate of accumulation of formazan, whether by
      increasing the concentration of the tetrazolium salt or by adding detergent,
      decreased susceptibility to inhibition by superoxide dismutase or by O2. These
      results are accommodated by a scheme of reactions the essence of which is the
      univalent reduction of the tetrazolium to an uncharged tetrazoinyl radical which
      can reduce O2 to O2- or which can partition into the detergent micelles and there
      dismute to generate the stable formazan.

PMID- 7503559
TI  - Interaction with membranes of cytochrome c554 from Nitrosomonas europaea.
AB  - Two c-cytochromes extrinsically bound to the membranes of Nitrosomonas europaea
      have been identified. One is the tetraheme cytochrome c554, a protein previously
      described as soluble and periplasmic. Depending on the concentration of Fe and Cu
      in the growth medium, from 50 to 100% of the total cellular cytochrome c554 is
      membrane-associated. The cytochromes c554 found in the soluble or membrane
      fractions are identical in the spectroscopic, chromatographic, or primary
      structural properties examined. The interaction of cytochrome c554 with membranes
      is ionic in nature; it is disrupted by high concentrations of salt. Both membrane
      derived and periplasmic forms of cytochrome c554 rebind tightly to membranes
      which have been washed free of the cytochrome. Cytochrome c554 binds to
      phospholipid vesicles, suggesting that phospholipids may play a role in the
      interaction of this cytochrome with the membrane. During the oxidation of NH2OH,
      the ability of the soluble hydroxylamine oxidoreductase (HAO) to transfer
      electrons to its natural electron acceptor, cytochrome c554, is substantially
      impaired when the latter is bound to phospholipid vesicles. The second c
      cytochrome associated with membranes in N. europaea is identified as HAO based on
      its catalytic activity and the presence of a 464-nm ferrous absorption band. A
      small fraction of HAO is found to be membrane-bound and only in cells grown under
      low Fe/low Cu. This subpopulation of HAO can be released from the membranes
      without detergents.

PMID- 7503560
TI  - Purification of human matrilysin produced in Escherichia coli and
      characterization using a new optimized fluorogenic peptide substrate.
AB  - Human promatrilysin (matrix metalloproteinase-7) has been produced in Escherichia
      coli as an N-terminal fusion protein with ubiquitin. The insoluble product was
      solubilized, refolded, and activated with amino-phenylmercuric acetate.
      Activation of the fusion protein demonstrated kinetics and intermediates that
      were very similar to those observed during activation of promatrilysin produced
      in Chinese Hamster Ovary (CHO) cells. Following activation, matrilysin was
      purified to > 95% homogeneity using a Sepharose-Pro-Leu-Gly-NHOH affinity column.
      The matrilysin purified by this procedure is indistinguishable from the enzyme
      purified from CHO cells with respect to the kinetic parameters for hydrolysis of
      a peptide substrate and the ability to obtain diffraction quality crystals in the
      presence of an inhibitor of the enzyme. Additionally, to facilitate detailed
      kinetic analyses of matrilysin, a new fluorogenic peptide substrate with the
      optimized sequence Dnp-Arg-Pro-Leu-Ala-Leu-Trp-Arg-Ser (Dnp, dinitrophenyl) has
      been synthesized. This peptide is the best substrate developed for matrilysin
      thus far with Km and kcat values of 26 microM and 5.0 s-1, respectively.

PMID- 7503561
TI  - High-level expression and purification of coffee bean alpha-galactosidase
      produced in the yeast Pichia pastoris.
AB  - alpha-Galactosidase isolated from coffee beans cleaves the terminal alpha
      galactose residues from oligosaccharide chains on blood group B red cells, thus
      generating group O cells. Such enzymatically converted red cells not only
      maintain full erythrocyte integrity and viability in vitro, but also demonstrate
      immune tolerance and a normal life span in vivo. In order to produce large
      quantities of recombinant alpha-galactosidase for use in the study of blood-type
      conversion, we subcloned the cDNA coding for coffee bean alpha-galactosidase into
      the EcoRI site of the vector pPIC9 in order to express the enzyme in Pichia
      pastoris, a methylotrophic yeast strain. After P. pastoris transformation,
      colonies were screened for high-level expression of alpha-galactosidase, based on
      enzyme activity. In order to increase enzyme production, the growth conditions in
      the shake flask culture and fermentor culture were optimized. Under the
      conditions applied, biologically active alpha-galactosidase was produced and
      secreted into the culture medium at a level of approximately 0.4 g per liter of
      the fermentor culture. The protein was purified to apparent homogeneity by a
      simple chromatography procedure, as suggested by a single band of 41 kDa on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its homogeneity was
      further confirmed by chromatofocusing and N-terminal sequencing. P. pastoris
      appears to be the choice as host for the large-scale production of recombinant
      alpha-galactosidase used for blood type conversion.

PMID- 7503562
TI  - Resolution of pyridoxal 5'-phosphate from O-acetylserine sulfhydrylase from
      Salmonella typhimurium and reconstitution of apoenzyme with cofactor and cofactor
      analogues as a probe of the cofactor binding site.
AB  - A procedure has been developed to prepare the apoenzyme of O-acetylserine
      sulfhydrylase (apoOASS) by first converting the native enzyme to the alpha
      aminoacrylate intermediate and dialyzing against 5 M guanidinium chloride.
      Aposulfhydrylase is stable for at least a month in buffers containing phosphate
      or phosphate analogues. Reconstitution of aposulfhydrylase with pyridoxal 5'
      phosphate (PLP), 2'-methyl PLP (2'-MePLP), and pyridoxal 5'
      deoxymethylenephosphonate (PDMP) results in enzymatically competent proteins.
      Pyridoxal in the absence and presence of phosphate and pyridoxal 5'-phosphate
      monomethyl ester are unable to form a Schiff base with apoOASS. The
      reconstitution of apoOASS with PLP is highly cooperative judged by the initial
      rate of activity regained and shows no evidence of saturation with PLP. The
      reconstituted enzymes have been studied using 31P NMR spectroscopy. The 31P NMR
      of the aposulhydrylase reconstituted with PLP exhibits a chemical shift of 5.2
      ppm, identical to that of native enzyme. The latter has been interpreted in terms
      of a strong ionic interaction between enzyme and the 5'-phosphate of PLP (P. F.
      Cook, S. Hara, S. Nalabolu, and K. D. Schnackerz, 1992, Biochemistry 31, 2298
      2303). Reconstitution with 2'-MePLP gives a lower chemical shift of 4.95 ppm,
      suggesting a weaker ionic interaction at the 5'-phosphate when compared to native
      enzyme. The PDMP-reconstituted enzyme gives a chemical shift of 23.7 ppm,
      consistent with the monoanionic form of the bound phosphonate. All of the
      chemical shifts are pH independent. The apoenzyme has also been reconstituted
      with pyridoxal 5'-sulfate. Although the resulting enzyme is not active in the
      overall reaction, it forms the external Schiff base. The PDMP- and 2'-MePLP
      reconstituted enzymes have also been studied in the presence of amino acid
      reactants and analogues, and results are discussed in terms of the mechanism of
      OASS.

PMID- 7503563
TI  - Bee venom phospholipase A2 is recognized by the macrophage mannose receptor.
AB  - A high affinity and a specific binding site for bee venom PLA2 was found on the
      surface of J774E macrophages. The binding sites for bee venom PLA2 are entirely
      different from the binding sites for pancreatic and snake venom PLA2 as revealed
      by competition experiments. Binding and uptake of bee venom PLA2 by J774E
      macrophages was shown to be competed by mannose-BSA, glucose-BSA, N
      acetylglucosamine-BSA, but not by galactose-BSA, indicating that the binding of
      bee venom PLA2 is probably mediated by macrophage mannose receptor. An affinity
      labeling experiment revealed that the bee venom PLA2 specifically binds to a
      single polypeptide with a mass of approximately 180 kDa. Moreover, the affinity
      labeled protein component, i.e., the binding site, was not detected in the
      presence of excess mannose-BSA, suggesting that mannose-BSA and the bee venom
      PLA2 bind to the same site on macrophages. These observations were further
      supported by the binding of bee venom PLA2 to cells which are known to express
      the mannose receptor and by specific binding of bee venom PLA2 to the purified
      mannose receptor. These data confirm that bee venom PLA2 binding to macrophages
      is mediated through the mannose receptor.

PMID- 7503564
TI  - Decrease of red cell membrane fluidity and -SH groups due to hyperglycemic
      conditions is counteracted by alpha-lipoic acid.
AB  - Human red cell membranes (ghosts) were treated by 5 min of incubation with
      fasting or hypo- and hyperglycemic concentrations of D-glucose. This simulation
      of nondiabetic or diabetic conditions revealed an influence on membrane fluidity
      and on protein -SH reactivity. Protein -SH groups, measured with Ellman's
      reagent, generally behave in the same way as membrane fluidity determined with
      diphenylhexatriene. Maximal values were obtained with 5 mM D-glucose, whereas
      decrease was observed above 10 mM D-glucose. Addition of alpha-lipoic acid (4
      nmol/mg protein) resulted in a significant increase in membrane fluidity and
      titratable -SH groups at glucose concentrations of 10 mM and above.
      Dithiothreitol diminished titrable-SH groups and did not restore membrane
      fluidity. 2-Mercaptopropionylglycine was only effective in restoration of -SH
      groups. By contrast to D-glucose, other sugars such as L-glucose, D-fructose, or
      sucrose revealed no comparable changes on membrane fluidity and titratable
      membrane -SH groups between concentrations of 5 and 10 mM. The hyperglycemic
      effects of D-glucose were corroborated with isolated, reconstituted membrane
      proteins and erythrocyte glucose carrier, indicating that, in general, the
      observed divergent biochemical/biophysical changes of the red cell membrane are
      influenced by the glucose transport protein GluT1. The natural R-form and the S
      form of alpha-lipoic acid were compared with racemic R-/S-forms for their
      efficiencies in alterations of red cell membrane fluidity. Decreased fluidities
      in presence of 10 mM glucose were found to be influenced in differentiated ways:
      the S-form was highly active in increasing fluidity at 4 nmol/mg and increasingly
      less active up to 20 nmol/mg protein. By contrast the R-form of lipoic acid was
      moderately efficient in increasing fluidity through a larger concentration range
      between 4 and 80 nmol/mg protein.

PMID- 7503565
TI  - Application of a double isotopic labeling method to a study of the interaction of
      mitochondrially bound rat brain hexokinase with intramitochondrial compartments
      of ATP generated by oxidative phosphorylation.
AB  - gamma-Labeled ATP was produced by rat brain mitochondria utilizing [32P]Pi as
      substrate for oxidative phosphorylation. The 32P/14C ratio of Glc-6-P produced by
      the endogenous mitochondrially bound hexokinase (ATP:D-hexose 6
      phosphotransferase, EC 2.7.1.1) using [U-14C]Glc as substrate was determined as a
      function of time after initiation of oxidative phosphorylation. This same ratio
      was determined for Glc-6-P formed by added yeast hexokinase using
      extramitochondrial ATP as substrate. The specific activity of ATP formed by
      oxidative phosphorylation was manipulated either by initiating the reaction with
      labeled Pi and subsequently adding excess unlabeled Pi or by initiating the
      reaction with unlabeled Pi and introducing the labeled substrate at a later time.
      The 32P/14C ratio of Glc-6-P formed by yeast hexokinase, reflecting the specific
      activity of ATP in the extramitochondrial space, was rapidly responsive to such
      manipulations, but the corresponding changes in the 32P/14C ratio of Glc-6-P
      produced by the endogenous hexokinase were markedly different. The results are
      consistent with the view that mitochondrially bound hexokinase does not utilize
      extramitochondrial ATP as substrate but rather is functionally coupled to a
      discrete intramitochondrial compartment of ATP produced by oxidative
      phosphorylation.

PMID- 7503566
TI  - Mature cathepsin L is substantially active in the ionic milieu of the
      extracellular medium.
AB  - The activity of cathepsin L is affected by ionic strength, resulting in the
      measured pH optimum being higher in acetate-4-morpholineethane sulfonic acid
      (MES)-Tris buffers of constant ionic strength than in phosphate buffers of
      constant molarity (and hence varying ionic strength). In acetate-MES-Tris and
      phosphate buffers of constant ionic strength across the pH range, the catalytic
      constant, kcat, generally peaked at ca. pH 6.5 and essentially independently of
      ionic strength. Km values, of ca. 5 microM, manifested a slight rising trend with
      increasing ionic strength, with a sharp increase to 20-25 microM, specifically at
      pH 6.5 and I = 0.4. At physiological ionic strengths, the specific buffer ions
      present affected the activity of mature cathepsin L, kcat/Km declining above pH
      6.5 in phosphate buffer, but only above pH 7 in acetate-MES-Tris buffer. In
      Hanks' balanced salt solution, a model of the extracellular fluid, measured
      values at pH 7.2 were kcat, 18.9 s-1; Km, 13.5 microM; and kcat/Km, 1.4 x 10(6) M
      1 s-1. The stability of cathepsin L in the physiological pH range was also
      differentially affected by the specific buffer ions, generally in parallel with
      the enzyme activity. In Hanks' balanced salt solution, mature cathepsin L was
      substantially active and stable, having a half-life of 179 s at pH 7.2 and 657 s
      at pH 6.8 (the peritumor pH).

PMID- 7503567
TI  - Purification and characterization of allantoate amidohydrolase from Bacillus
      fastidiosus.
AB  - Allantoate amidohydrolase from Bacillus fastidiosus was purified 170-fold to
      homogeneity as judged by isoelectric focusing and nondenaturing and sodium
      dodecyl sulfate polyacrylamide gel electrophoresis. The molecular mass was
      estimated to be 128 kDa. The enzyme appeared to be a homodimer with a subunit
      molecular mass of 66 kDa. The enzyme has an isoelectric point of 5.6. Allantoate
      amidohydrolase is a Mn(2+)-dependent enzyme exhibiting a pH optimum around 8.8.
      Its Km value for allantoate was estimated to be 9 mM. Similar to other microbial
      allantoate amidohydrolases the enzyme can be reversibly activated and
      inactivated. No indication for the involvement of arginine, lysine, and cysteine
      residues in the catalytic action of the enzyme was obtained. Diethylpyrocarbonate
      strongly inhibited the enzyme activity, indicating the involvement of histidine
      or tyrosine residues in catalytic action. However, no recovery was obtained by
      treatment with hydroxylamine as would be expected if such residues were modified.
      The enzyme could be reversibly denatured by urea, guanidine, and sodium dodecyl
      sulfate.

PMID- 7503568
TI  - Vitiligo treatment with a combination of PUVA therapy and epidermal autografts.

PMID- 7503569
TI  - Osteoporosis is a toxic effect of long-term etretinate therapy.
AB  - BACKGROUND AND DESIGN: Osteoporosis has been observed with chronic
      hypervitaminosis A but has not been established as a toxic effect of synthetic
      retinoid therapy in humans. This cross-sectional study was designed to assess
      bone mineral density (BMD) during long-term therapy with the retinoids etretinate
      or isotretinoin. Twenty-four patients were evaluated for osteoporosis with the
      standard techniques: single- and dual-photon absorptiometry. They received 50 g
      or more of etretinate (15 patients) or isotretinoin (nine patients) for 2 years
      or longer for the treatment of skin disease (ichthyosis [nine patients], Darier's
      disease [six patients], xeroderma pigmentosum [four patients], skin cancer [three
      patients], or psoriasis [two patients]). In each of the two treatment groups,
      BMDs (measured in grams per square centimeter) were measured at five standard
      sites (ie, lumbar spine, femoral neck, trochanter, Ward's triangle, and radius)
      and evaluated against a standardized database to control for age, sex, and
      weight. In addition, for each measurement site, BMDs (controlled for age, sex,
      and weight) were compared between the two groups, as a direct control for each
      other. OBSERVATIONS: Compared with those of the age-, sex-, and weight-matched
      controls, the BMD values of the etretinate group were significantly decreased at
      four of the five measurement sites: femoral neck (90.6%, P = .0001), Ward's
      triangle (87.8%, P = .0001), trochanter (87.8%, P = .0012), and radius (85.0%, P
      = .039). In contrast, the BMDs in the isotretinoin group did not differ from
      control values except for an elevation at the lumbar spine (P = .039). When the
      two groups were compared, the mean BMDs were significantly lower in the
      etretinate group when measured at the lumbar spine, trochanter, and radius (P <
      .05). CONCLUSIONS: This study identified osteoporosis in patients who received
      long-term therapy with etretinate but not isotretinoin. Prospective studies of
      BMD would be useful to further define retinoid-associated osteoporosis.

PMID- 7503570
TI  - Clinicopathologic correlation in erythema multiforme and Stevens-Johnson
      syndrome.
AB  - BACKGROUND AND DESIGN: To confirm the recent hypothesis that the spectrum of
      severe erythema multiforme (EM) is actually composed of two different disorders,
      we retrospectively studied 38 such cases, particularly in regard to their
      histopathologic features. Based on photographs and a recent proposal, the cases
      were classified as EM major when the eruption consisted of typical or raised
      atypical target lesions located on the extremities and/or the face or as Stevens
      Johnson syndrome when the eruption consisted of flat atypical target lesions or
      purpuric macules that were widespread or distributed on the trunk. The cases were
      also assessed for causal agent. A biopsy specimen was obtained in each case.
      Several histologic parameters were analyzed (and scored) without clinical data
      and correlated to the clinical pattern. These parameters were first studied in a
      global assessment and then in a detailed evaluation. RESULTS: The global
      assessment showed two different histological patterns: (1) a predominantly
      inflammatory pattern characterized by a lichenoid infiltrate and epidermal
      necrosis that mainly affected the basal layer; and (2) a predominantly necrotic
      pattern in which major epidermal necrosis and minimal inflammatory infiltration
      were found. The former pattern was associated with EM major, the latter with
      Stevens-Johnson syndrome (P < .001) and with drug-related cause (P < .001). The
      detailed evaluation showed also less epidermal necrosis, and more dermal
      inflammation, and more exocytosis in EM major. Conversely, there was more
      epidermal necrosis, less dermal inflammation, and less exocytosis in Stevens
      Johnson syndrome. The difference was statistically significant for the
      inflammation and exocytosis. CONCLUSIONS: This study suggests that the two
      different symptomatologies in the spectrum of severe EM correlate with two
      different patterns of histopathologic changes. A prospective multicentered study
      should be conducted to definitively characterize these entities.

PMID- 7503571
TI  - A transgenic mouse model provides a novel biological assay of topical
      glucocorticosteroid potency.
AB  - BACKGROUND AND DESIGN: A homozygous line of transgenic mice that expresses the
      human elastin promoter/CAT (chloramphenicol acetyltransferase) reporter gene
      construct in a tissue-specific and developmentally regulated manner is presented.
      Previous studies have shown that subcutaneous injections of various
      glucocorticosteroids up-regulate the human transgene in the mouse skin
      potentially through their interaction with three putative glucocorticosteroid
      responsive elements contained within the human elastin promoter. In this study,
      we propose the use of these transgenic mice as a model system for assaying the
      potency of various topical glucocorticosteroid preparations. RESULTS: In the
      first set of experiments, three different commercially available topical
      glucocorticosteroid creams, 2.5% Hytone (2.5% hydrocortisone) (Dermik
      Laboratories, Fort Washington, Pa), Cutivate (0.05% fluticasone propionate)
      (Glaxo Inc, Research Triangle Park, NC), and Temovate (0.05% clobetasol
      propionate) (Glaxo Inc) (being classified into class VII, V, and I steroids,
      respectively) were applied to the skin of transgenic mice, with Eucerin
      (Beiersdorf Inc, Lindenhurst, NY) as the control cream. In a series of six
      experiments, Hytone 2.5% cream caused a 3.1-fold increase on the average, with
      Cutivate and Temovate creams resulting in 2.2-fold and 12.4-fold increases in CAT
      activity over control, respectively. Next, two different preparations of
      diflorasone diacetate 0.05% cream (Florone [class III] and Psorcon [class II],
      both from Dermik Laboratories), formulated with different vehicles, were
      compared. Psorcon caused a 22.8-fold increase in CAT activity over the control
      compared with a 4.4-fold increase for Florone. However, an assay comparing
      Psorcon ointment (class I) and Psorcon cream (class II) showed no statistically
      significant difference in their potencies. CONCLUSIONS: These preliminary
      findings suggest the usefulness of these transgenic mice as a model system for
      assaying the potency of topical glucocorticosteroid preparations. Discrepancies
      between our data and the published classification of some topical steroids may
      result from anatomic differences between human and murine skin, with mouse skin
      much thinner, Alternatively, the discrepancies may reflect the fact that our
      assay measures the biological activity of these steroids on gene transcription,
      while previous ranking is based on their vasoconstrictive activity.

PMID- 7503573
TI  - Disseminated acanthamebiasis in patients with AIDS. A report of five cases and a
      review of the literature.
AB  - BACKGROUND: Acanthamoeba and Leptomyxida are free-living amebae that cause
      granulomatous amebic encephalitis, a rare, slowly progressive, fatal neurologic
      process seen in immunosuppressed hosts. In addition, these organisms produce
      disseminated cutaneous lesions and involve other organs, particularly in patients
      with the acquired immunodeficiency syndrome (AIDS). RESULTS: We report five cases
      of disseminated acanthamebiasis in patients with AIDS, each with cutaneous
      manifestations but lacking central nervous system involvement. The medial CD4+ T
      cell count was 0.024 x 10(9)/L. Skin lesions included pustules, subcutaneous and
      deep dermal nodules, and ulcers, most often seen on the extremities and face.
      Histopathologically, both pustular and vasculitic changes were observed; in all
      cases, the microscopic identification of organisms was difficult because of the
      macrophagelike appearance of the microbes in routine sections. CONCLUSIONS: Skin
      lesions are the most common reported presentation of infections caused by
      Acanthamoeba and Leptomyxida organisms in patients with AIDS, a minority of whom
      have central nervous system manifestations. A high index of suspicion is
      necessary for both the dermatologist and the dermatopathologist. Prognosis is
      guarded, but early treatment using a combination of intravenous pentamidine and
      oral fluconazole, sulfadiazine, and flucytosine may be beneficial.

PMID- 7503572
TI  - Cutaneous presentations of lymphoma in human immunodeficiency virus disease.
      Predominance of T cell lineage.
AB  - BACKGROUND AND DESIGN: Most non-Hodgkin's lymphomas in patients with human
      immunodeficiency virus infection are of B-cell lineage. Cutaneous lymphoma in the
      human immunodeficiency virus disease has not been systematically reviewed. We
      studied 25 patients with both human immunodeficiency virus infection and
      cutaneous presentations of lymphoma, using immunohistochemistry and in situ
      hybridization for Epstein-Barr virus. RESULTS: Two groups of patients were
      discerned: (1) those with conditions similar to mycosis fungoides or Sezary
      syndrome with an indolent course (n = 8) and (2) those with nodules or papules,
      greater immunosuppression, a rapid clinical course, and large cell lymphoma seen
      on biopsy specimens (n = 17). The epidermotropic lymphomas were T-cell lineage
      and CD30-. Thirteen of the large cell lymphomas were also of the T-cell type, and
      71% were CD30+. Epstein-Barr virus was absent in the epidermotropic lymphomas,
      but it was present in 73% of the nonepidermotropic cases. CONCLUSIONS: Two forms
      of human immunodeficiency virus-associated cutaneous lymphoma were found:
      indolent disease resembling mycosis fungoides or Sezary syndrome and large cell
      lymphomas with a poor prognosis, whose cells often had a CD30+ T-cell phenotype
      and harbored the Epstein-Barr virus.

PMID- 7503574
TI  - The diagnostic value of morphometry on blood lymphocytes in erythrodermic actinic
      reticuloid.
AB  - BACKGROUND: As the differential diagnosis of erythrodermic actinic reticuloid vs
      Sezary syndrome (SS) can be very difficult, we examined the value of the nuclear
      contour index (NCI) on blood lymphocytes as the criterion for differential
      diagnoses. The NCI is defined as the nuclear parameter divided by the square root
      of the nuclear area. Three different parameters were studied: mean NCI,
      percentage of cells with an NCI of 6.5 or greater, and the highest NCI. These
      indexes were studied on blood lymphocyte samples obtained from 10 patients with
      erythrodermic actinic reticuloid and were compared with the findings in 10
      patients with other benign forms of erythroderma and in seven patients suffering
      from SS. RESULTS: The patients with erythrodermic actinic reticuloid differed
      significantly from the group with SS regarding the percentage of cells with an
      NCI of 6.5 or greater and the highest NCI, but not when the mean NCI was
      considered. All three parameters revealed nonsignificant results for
      erythrodermic actinic reticuloid compared with other benign forms of
      erythroderma. The group with SS differed significantly from the patients with
      other benign forms of erythroderma regarding all three parameters. By combining
      three morphometric criteria (mean NCI, > or = 5.5; > 30% lymphoid cells with an
      NCI of > or = 6.5; and highest NCI, > or = 11.5), all patients with erythrodermic
      actinic reticuloid or other benign forms of erythroderma and six of the seven
      patients with SS were correctly classified. CONCLUSION: Our data indicate that
      assessment of the NCI on peripheral blood lymphocytes is of value in the
      differential diagnosis of erythrodermic actinic reticuloid vs SS.

PMID- 7503575
TI  - Photosensitivity associated with combined UV-B and calcipotriene therapy.
AB  - BACKGROUND: Ultraviolet B phototherapy is an effective agent for the treatment of
      psoriasis; its most frequent acute side effect is burning of the skin. It has
      been combined with various other topical or systemic agents to augment
      therapeutic effect. Recently, UV-B therapy has been used with calcipotriene
      ointment (Dovonex, Westwood-Squibb, Buffalo, NY), a new vitamin D analogue.
      OBSERVATIONS: We report four cases of chronic plaque psoriasis that developed in
      patients who used UV-B phototherapy for a substantial period without ill effects
      and in whom photosensitivity reactions within psoriatic plaques developed after
      calcipotriene ointment was added, without changes in their UV-B dosage or
      frequency of treatment. The time from starting calcipotriene therapy to the
      development of photosensitivity ranged from 4 to 28 days, and the number of UV-B
      exposures during this period varied between one and 12 treatments. The mean UV-B
      dose at burning was 1114mJ/cm2. Twenty-two patients had used calcipotriene in
      combination with UV-B therapy of a total of 103 UV-B-treated patients during the
      period when the adverse events occurred. Half these patients started
      calcipotriene therapy prior to starting treatment with UV-B. However, cases of
      photosensitivity occurred only in the remaining half of the patients in whom
      calcipotriene therapy was added during UV-B therapy. Combined therapy was able to
      be continued or resumed in two patients by reduction of the UV-B dose. In three
      cases, phototesting, confirmed greater photosensitivity to calcipotriene-treated
      skin than to skin to which hydrated petrolatum was applied. CONCLUSIONS:
      Calcipotriene ointment should be introduced with caution in patients already
      receiving UV-B phototherapy, particularly those receiving high doses of UV-B. The
      mechanism of this photosensitivity reaction is unknown. This increased
      sensitivity to UV-B may be a result of the effect of calcipotriene on stratum
      corneum thickness, epidermal melanization, a result of its effect on the
      inflammatory reaction to UV-B irradiation, or, possibly, because it is a
      phototoxic agent.

PMID- 7503576
TI  - Neonatal pemphigus foliaceus.
AB  - BACKGROUND: Pemphigus refers to a group of autoimmune blistering diseases of the
      skin. Of the two major types of pemphigus, pemphigus vulgaris and pemphigus
      foliaceus, only pemphigus vulgaris has been known to affect newborn infants via
      passive transfer of maternal IgG antibodies across the placenta. Although
      pemphigus foliaceus antibodies have also been shown to cross the placenta, never
      before has a newborn been clinically affected. We report the first of neonatal
      pemphigus foliaceus confirmed by both clinical presentation and
      immunofluorescence studies. OBSERVATIONS: The distinguishing factors in this case
      were high antibody titers by indirect immunofluorescence present in both the
      mother and her fetus (1:640 and 1:80, respectively). CONCLUSIONS: A threshold of
      fetal antibody titer ( > 1:40) may need to be surpassed before neonatal disease
      can occur in pemphigus foliaceus. The likelihood of reaching this threshold has
      been shown to be increased with higher maternal antibody titers. Thus, strict
      control of maternal pemphigus foliaceus should lower the incidence of placental
      antibody transfer and improve neonatal outcome.

PMID- 7503577
TI  - Epidermodysplasia verruciformis as a model of human papillomavirus-induced
      genetic cancer of the skin.
AB  - BACKGROUND: Epidermodysplasia verruciformis is a rare lifelong disease that has
      raised an enormous interest since it is a model of cutaneous genetic cancer
      induced by specific human papillomaviruses. OBSERVATIONS: The interacting
      immunogenetic and environmental factors, especially UV irradiation, result in the
      inability of the patients' immune system to respond to epidermodysplasia
      verruciformis-specific human papillomaviruses. The local immunosuppression is an
      effect, at least in part, of the overproduction of tumor necrosis factor alpha
      and transforming growth factor beta1 and of the excessive formation of cis
      urocanic acid. CONCLUSIONS: Epidermodysplasia verruciformis is a model not only
      of cutaneous viral oncogenesis but also of local defense mechanisms in the
      progression of human papillomavirus-associated cancers.

PMID- 7503578
TI  - Iatrogenic osteoporosis.

PMID- 7503579
TI  - The evolution of vitamin D analogues for the treatment of psoriasis.

PMID- 7503580
TI  - Sporotrichoid nodules in an immunocompromised host. Cutaneous emboli of Fusarium.

PMID- 7503581
TI  - Acute localized bullous eruption in a boy. Bullous reaction to insect bites.

PMID- 7503582
TI  - Sudden, extensive induration of arms, abdomen, and legs.

PMID- 7503583
TI  - A seborrheic keratosislike lesion. Intraepidermal epithelioma of Borst-Jadassohn.

PMID- 7503584
TI  - Regular use of sunscreen on vitamin D levels.

PMID- 7503585
TI  - Is the combination of tetracycline and nicotinamide therapy alone effective in
      pemphigus?

PMID- 7503586
TI  - Intradermal fluorouracil and epinephrine injectable gel for treatment of
      psoriatic plaques.

PMID- 7503587
TI  - Identification of Borrelia afzelii in a juxta-articular fibroid nodule from a
      human immunodeficiency virus-positive patient with acrodermatitis chronica
      atrophicans.

PMID- 7503588
TI  - Assessment of effect of photosensitizers on cytotoxicity of photodynamic therapy
      in human breast cancer cell cultures.
AB  - BACKGROUND: Photodynamic therapy (PDT) might be of clinical value for patients
      with breast cancer with local recurrences or metastasis. However, there is a need
      for improved photosensitizers that are effective in combination with laser light
      and have few, if any, side-effects. We evaluated in vitro the effectiveness of a
      second generation photosensitizer by testing the influence of laser light on cell
      cultures of a human breast carcinoma cell line, incubated with meta
      tetrahydroxyphenylchlorin (m-THPC) (= Temoporfin). EXPERIMENTAL DESIGN: Five
      thousand MCF-7 cells were plated in 96-well plates. Forty-eight hours before
      laser treatment, the cells were plated to achieve a monolayer configuration.
      Twenty-four hours after plating, they were incubated with m-THPC. On day 6 after
      treatment with m-THPC we lysed the cells to extract the intracellular ATP that
      correlates with the number of living cells. The ATP-CVA was used to assess the
      cytotoxicity of the tested photosensitizer m-THPC at various concentrations and
      the relevant laser light alone prior to their combination after six days of
      culture. RESULTS: We found a dose-response for m-THPC alone ranging from 2 to 16
      micrograms/ml. The calculated inhibition concentration to produce 50% cell kill
      (IC50) was 4.55 micrograms/ml. We also observed a very low cytotoxicity for laser
      irradiation alone but a very strong cell kill for the combination of m-THPC
      together with laser light. CONCLUSIONS: PDT gave almost total cell kill at m-THPC
      concentrations that are not toxic in vitro.

PMID- 7503589
TI  - A novel human monoclonal antibody against cervical cancer: its immunoreactivity
      with normal tube and ovary and with ovarian tumor tissue.
AB  - 1-1-2D, a novel human monoclonal antibody (MAb) raised against cervical cancer,
      was examined for its immunohistochemical reactivity with ovarian cancer. Six of
      10 ovarian cancer cell lines showed positive staining, while 3 of 5 cervical
      cancer cell lines were positive. Among tumor tissues, 15 of 18 (83%) ovarian
      serous cystadenocarcinomas and 10 of 12 (83%) ovarian clear cell adenocarcinomas
      were positive. We also performed immunohistochemical staining of the same cancer
      specimens with OC 125 and compared their reactivity. The frequency of positivity
      was similar, but the reactivity of the two MAbs was different. 1-1-2D stained the
      apical surface of the glandular epithelial cells and secretory products of the
      gland. On the other hand, OC 125 stained the cytoplasm as well as the plasma
      membrane of the glandular epithelial cells. These results suggest that 1-1-2D MAb
      recognizes a different antigen from that recognized by OC 125.

PMID- 7503590
TI  - A sensitive enzyme immunoassay for pregnancy-associated plasma protein A (PAPP
      A): a possible first trimester method of screening for Down syndrome and other
      trisomies.
AB  - Pregnancy-associated plasma protein A (PAPP-A) is a large glycoprotein produced
      mainly by the trophoblast during pregnancy and released into the maternal
      circulation. Its biological function is unknown. In the second trimester i.e.
      when Down syndrome (DS) screening is routinely performed, the level of maternal
      serum PAPP-A was found to be within the normal range in pregnancies affected by
      fetal trisomy 21. However, PAPP-A was shown to be a potent marker for DS before
      14 weeks of gestation. Only radioimmunoassays (RIAs) based on labelled antigen
      competition reached the required sensitivity for early pregnancy PAPP-A
      determinations; but they have a very short shelf life due to inherent tracer half
      life and, in the case of PAPP-A, instability of the labelled antigen after three
      weeks. We describe a convenient and novel enzyme immunoassay (ELISA) with high
      sensitivity and a long shelf life.

PMID- 7503591
TI  - Prenatal diagnosis by transabdominal chorionic villus sampling in the second and
      third trimesters.
AB  - From October 1989 through December 1993, 124 pregnant women (114 in the second
      trimester and 10 in the third trimester) underwent transabdominal chorionic
      villus sampling (CVS) for prenatal molecular or cytogenetic diagnosis. The mean
      gestational age was 18.2 weeks. Indications for CVS comprised single gene disease
      (72%), fetal anomalies detected by ultrasound (17%), advanced maternal age (6%),
      and previous siblings with chromosomal aberration (5%). Among the 89 fetuses at
      risk for single gene disease, 20 were diagnosed as affected by DNA analysis.
      Among the 35 fetuses at risk for chromosomal anomaly, 4 had trisomy, 3 had a
      45,XO karyotype and 2 had a structural chromosomal abnormality. The miscarriage
      rate was 1.8% (2/114) and the spontaneous preterm birth rate was 2.4% (3/124). No
      maternal or other fetal complications occurred. This study suggested that second-
      and third trimester CVS is a safe and useful method for prenatal diagnosis.

PMID- 7503593
TI  - Unsuccessful treatment of tubal pregnancy by shock wave lithotripsy.

PMID- 7503592
TI  - Guillain-Barre syndrome in pregnancy--two case reports and a discussion on
      management.

PMID- 7503594
TI  - Postmenopausal virilization due to ovarian hyperthecosis.
AB  - A case of a 66-year-old obese woman with type II diabetes mellitus and a 4 year
      history of virilism is presented. After removal of the ovaries the raised
      testosterone levels returned to normal and signs of virilism gradually receded.
      The histological finding of nodular hyperthecosis of the ovaries is discussed in
      relation to hyperinsulinaemia.

PMID- 7503596
TI  - The relativity of alternative medicine.

PMID- 7503595
TI  - A report on the perinatal diagnosis of 4 cases of cardiac tumors.
AB  - Since 1973, we have identified 4 cardiac tumors by ultrasonography in fetal or
      early postnatal life. Tuberous sclerosis was diagnosed in three infants whose
      mother was also affected. The first infant died from acute cardiac failure after
      birth, and the second required cardiac surgery. The third infant had a cardiac
      tumor and a focal seizure at the age of 8 months. The cardiac tumor disappeared
      at the age of 2 years. The fourth cardiac rhabdomyoma may be the only sign of
      tuberous sclerosis.

PMID- 7503597
TI  - Fecal occult blood screening for colorectal cancer.
AB  - We critically analyzed the current literature on fecal occult blood testing as it
      pertains to colorectal cancer screening. We used articles published or referenced
      in the major English-language medical and gastroenterology journals for the last
      10 years. Large, randomized controlled trials, case-control and cohort studies,
      and other sources containing information pertinent to the application of fecal
      occult blood testing for colorectal cancer screening were selected. Although the
      fecal occult blood test results are capable of predicting the presence of
      colorectal cancers and polyps, the sensitivity is variable in different studies
      and low for the latter. Nevertheless, most reports of its use emphasize that a
      relatively high percentage of the cancers detected are early-stage lesions.
      Currently available methods for colorectal cancer screening are imperfect,
      thereby increasing the cost-effectiveness ratio. The fecal occult blood test
      remains a workable approach to reducing the mortality from colorectal cancer
      provided it is carried out with attention to important variables such as the need
      for compliance, including the compliance of physicians.

PMID- 7503598
TI  - Complementary medicine. What physicians think of it: a meta-analysis.
AB  - BACKGROUND: Complementary (or alternative) medicine has become a prevalent
      phenomenon in most industrialized countries. At present the evidence from
      randomized controlled trials investigating its effectiveness is fragmentary and
      therefore inconclusive. OBJECTIVE: To assess whether physicians perceive
      complementary medicine as useful and/or effective. METHOD: A literature search
      was performed to retrieve all relevant articles. Twelve surveys addressing this
      question were found and analyzed by evaluating perceived usefulness and/or
      effectiveness. RESULTS: The results show a remarkable variability between
      surveys. On average physicians perceive complementary medicine as moderately
      effective--the rating was 46 +/- 18 on a scale of 0 to 100 points. Young
      physicians seem to judge complementary medicine more optimistically than their
      more seasoned colleagues. There is no trend to suggest that complementary
      medicine is increasingly perceived as useful and/or effective. The data do not
      answer the question whether physicians view complementary medicine as a
      nonspecific powerful placebo or as specifically effective. CONCLUSION:
      Complementary medicine may be useful; however, the notion urgently needs to be
      tested in randomized controlled trials.

PMID- 7503599
TI  - Are lean smokers at increased risk of lung cancer? The Israel Civil Servant
      Cancer Study.
AB  - BACKGROUND: Whether leanness is related to an increased risk of lung cancer is
      controversial. OBJECTIVE: To examine the association of leanness with lung cancer
      incidence in a sample of Israeli men. METHODS: The 23-year lung cancer incidence
      (1963 through 1986) was determined by linkage to the Israel Cancer Registry in
      9975 male civil servants aged 40 through 69 years at initial examination in 1963.
      In 198,298 person-years of follow-up, 153 cases of lung cancer were identified.
      In 1963, body mass index (BMI) and cigarette smoking status were determined; in
      the 1968 reexamination, lung function tests were performed and BMI was
      reassessed. RESULTS: Adjusted for age, smoking, and city by Cox regression, BMI
      was exponentially inversely related to lung cancer incidence, with a relative
      risk of 2.3 (95% confidence interval [CI], 1.4 to 3.8) comparing the lowest fifth
      of BMI (< 22.93 kg/m2) with the highest. The association was evident in light,
      moderate, and heavy smokers. Among smokers, the adjusted relative risk was 3.7
      (95% CI, 1.9 to 7.3) for the lowest fifth of BMI. The associations were stronger
      for men in the lowest 10th of the BMI distribution (< 21.38 kg/m2). Controlling
      for lung function did not materially change the results. The adjusted population
      attributable fraction associated with the lowest fifth of BMI among smokers was
      20.4% (95% CI, 10.1% to 29.9%). Survival analysis showed that the association of
      BMI with lung cancer persisted throughout follow-up. CONCLUSIONS: The association
      shown between thinness and lung cancer incidence, particularly in smokers, was
      not attributable to the confounding factors studied, preclinical weight loss, or
      competing risks. Thinness in smokers may lead to, or may reflect, enhanced host
      susceptibility.

PMID- 7503600
TI  - Solitary thyroid nodule. Comparison between palpation and ultrasonography.
AB  - OBJECTIVE: To determine the accuracy of clinical palpation in the diagnosis of
      solitary thyroid nodule in comparison with ultrasonographic findings. METHODS:
      From a computerized database of 1774 patients with the diagnosis of nodular
      thyroid disease made from January 1990 through December 1991 at our institution,
      we retrieved and reviewed the medical records of the 193 patients who underwent
      ultrasonography of the thyroid (42 patients with multinodular glands on palpation
      were excluded). Nodules were categorized as "solitary" or "dominant nodule of a
      multinodular gland." Concordance rates were measured between results of palpation
      and ultrasonographic findings. RESULTS: Of 151 patients included in the study, 78
      had solitary nodules on ultrasonography and 73 had multiple nodules. Of those
      with multiple nodules, 49 had two nodules and 24 had three or more nodules. Of
      clinically palpable nodules, 89% were 1 cm or greater in diameter. In 72% of the
      patients with multiple nodules, the other nodules not identified on palpation
      were less than 1 cm in diameter. The overall concordance rate between the size of
      the solitary nodule or the dominant nodule in a multinodular gland estimated with
      clinical palpation and the actual size seen on ultrasonography was 72%. The
      relationship between multiple nodules and malignancy was not statistically
      significant. CONCLUSIONS: Our results suggest that (1) a palpable solitary nodule
      represents a multinodular gland in about 50% of patients, (2) clinical palpation
      is less sensitive than thyroid ultrasonography in identifying multiple nodules,
      and (3) palpation is reliable only if a nodule is at least 1 cm in diameter. We
      recommend that small, occult (impalpable) thyroid nodules not be considered
      clinically important; they do not warrant further evaluation unless
      ultrasonographic features suggest malignancy or the nodule increases in size.

PMID- 7503602
TI  - Pneumocystis carinii pneumonia in patients without AIDS, 1980 through 1993. An
      analysis of 78 cases.
AB  - BACKGROUND: Pneumocystis carinii pneumonia (PCP) occurs in immunocompromised
      patients without the acquired immunodeficiency syndrome (AIDS). There has been an
      increasing yearly number of cases of PCP in our patients without AIDS. OBJECTIVE:
      To determine the nature of the underlying disorder and previous immunosuppressive
      treatment in patients with PCP without AIDS. METHOD: A study of the charts of 78
      such patients admitted to our hospital from 1980 through 1993. RESULTS: The
      number of PCP cases per year increased during the period studied. All patients
      had an underlying disorder, either hematologic malignancy (49%), solid organ
      tumor (4%), vasculitis or other immunologic disorder (22%), or they had undergone
      renal transplantation (17%) or bone marrow transplantation (9%). Previous
      immunosuppressive medication consisted of prednisone or other corticosteroids in
      72 (92%) of 78 patients, cytotoxic drugs in 55 (71%) of 78 patients, both in 50
      (64%) of 78 patients, and none in one patient. Quantification of previous
      corticosteroid treatment showed a large variability among patients. The overall
      mortality rate for patients was 35% (27/78). Mortality was significantly higher
      in patients with a concomitant pulmonary infection (P = .01), an underlying
      disorder other than that which resulted in renal transplantation (P = .03),
      mechanical ventilation (P < .001), previous chemotherapy (P = .04), as well as
      previous cyclophosphamide treatment (P = .01). A trend toward a higher mortality
      in patients with previous corticosteroid use was detected (P = .06). CONCLUSION:
      Pneumocystis carinii pneumonia may complicate a variety of immunocompromised
      states, with considerable mortality. Pneumocystis carinii pneumonia occurred at
      all levels of immunosuppression; no threshold level could be defined.

PMID- 7503601
TI  - Therapeutic approaches in patients with candidemia. Evaluation in a multicenter,
      prospective, observational study.
AB  - OBJECTIVES: To evaluate the morbidity and mortality of Candida fungemia and to
      assess the efficacy of low- vs high-dose amphotericin B and fluconazole vs
      amphotericin B in patients with candidemia. METHODS: Multicenter, prospective,
      observational study of 427 consecutive patients with candidemia. RESULTS: The
      mortality rate for patients with candidemia was 34%. The mortality rate for
      patients with catheter-related candidemia in whom the catheters were retained was
      significantly higher than that of patients in whom the catheters were removed
      (41% vs 21%, P < .001). We found no overall difference in mortality in patients
      treated with low-dose (total amphotericin B dose of < or = 500 mg) (13%) vs high
      dose amphotericin B (total amphotericin B dose of > 500 mg) (15%), but the group
      treated with a low dose had fewer side effects (40%) than those treated with a
      high dose (55%) (P = .03). Fluconazole was as efficacious as amphotericin B in
      the therapy of candidemia, even when stratified by risk factors for mortality.
      Fewer side effects were seen with fluconazole (12%) compared with amphotericin B
      (44%) (P < .001). CONCLUSIONS: In selected patients with candidemia, low-dose
      amphotericin B was as efficacious as high-dose amphotericin B. Based on other
      studies and ours, fluconazole seems to be an alternative therapeutic option to
      amphotericin B in selected patients.

PMID- 7503603
TI  - Physiological predictors of increasing total and central adiposity in aging men
      and women.
AB  - BACKGROUND: Increasing levels of total and central body fat with advancing age
      contribute to the development of cardiovascular and metabolic disease. We
      examined gender-related differences and physiological predictors of the rate of
      increase in total and central body fat in men and women. METHODS: We studied 427
      healthy men (age range, 17 to 90 years) and 293 women (age range, 18 to 88
      years). We measured body fatness by hydrostatic weighing, central adiposity from
      the waist circumference, peak volume of oxygen utilization (VO2) from a treadmill
      test, leisure time physical activity (LTA) from a questionnaire, resting
      metabolic rate and respiratory quotient from indirect calorimetry, and energy
      intake from 3-day food diaries. RESULTS: Fat mass increased with age, and the
      rate was greater in women (r = .61; slope = 0.25 kg/y; P < .01) than in men (r =
      .43; slope = 0.16 kg/y; P < .01). Increasing fat mass in men and women was most
      strongly associated with declines in peak VO2 and LTA. Controlling for these
      variables reduced the increase in fat mass from 17% to 3% per decade in men and
      from 26% to 5% per decade in women. The increase in waist circumference with age
      was also greater in women (r = .53; slope = 0.28 cm/y) than in men (r = .39;
      slope = 0.18 cm/y; P < .01). Increasing waist circumference with age in men and
      women was most strongly associated with declines in LTA and peak VO2,
      respectively. Control for these variables reduced the age-related increase in
      waist circumference from 2% to 1% per decade in men and from 4% to 1% per decade
      in women. We observed no independent contribution of resting metabolic rate,
      respiratory quotient, menopause status, energy, or macronutrient intake to the
      age-related increase in fat mass and waist circumference. CONCLUSIONS: Our
      findings suggest that (1) the age-related increase in fat mass and waist
      circumference is greater in women than in men and (2) the physiological
      characteristics that reflect a decline in physical activity-related energy
      expenditure, rather than resting energy expenditure, are important predictors of
      the increases in total and central fatness. Lifestyle changes that increase the
      level of physical activity may be advantageous in blunting age-related increases
      in total and central body fatness.

PMID- 7503604
TI  - Albumin and nonprotein colloid solution use in US academic health centers.
AB  - BACKGROUND: Crystalloids, nonprotein colloids (NPCs), and albumin are used for
      many indications. The use of the least costly agent in situations where these
      products are clinically interchangeable can reduce health care costs. OBJECTIVES:
      To characterize the prescribing of albumin and NPC. To evaluate the
      appropriateness and cost implications of their use. METHODS: An observational
      study conducted in 15 academic health centers from April 11 through May 6, 1994,
      to assess the appropriateness of albumin and NPC use, based on "model" consensus
      derived indication guidelines. RESULTS: A total of 969 case report forms were
      evaluated. Albumin and NPCs were administered in 83% and 17% of the cases,
      respectively. Albumin and NPCs were administered mostly in the intensive care
      (50%) or operating room (31%) settings. The most common prescribers of these
      products were surgeons (45%) and anesthesiologists (20%). In 87% of cases,
      albumin or NPC was administered to reach a defined end point (eg, to achieve a
      target physiological state or to resolve a pathophysiological condition). Only
      one albumin recipient experienced an adverse event; no adverse events were noted
      with NPC administration. Approximately $203,000 was spent on albumin and NPC
      therapy for the 969 cases; $49,702 (24%) was spent on appropriate
      administrations, $124,939 (62%) on inappropriate administrations, and $28,014
      (14%) on unevaluated indications. CONCLUSIONS: Evaluated against model
      guidelines, most of the albumin and NPC use in the study was found to be
      inappropriate. The need for institutions to define and implement guidelines that
      focus on the cost-efficient use of these agents is recommended in an increasingly
      cost-conscious health care environment.

PMID- 7503605
TI  - Misdiagnosing delirium as depression in medically ill elderly patients.
AB  - BACKGROUND: Delirium, a common and often overlooked syndrome in acutely ill
      elderly patients, may present with signs and symptoms of depression. OBJECTIVE:
      To determine (1) how often health care providers mistake delirium for a
      depressive disorder in older hospitalized patients referred to a psychiatric
      consultation service for depressive symptoms and (2) which signs and symptoms of
      depression and delirium characterize these patients. SUBJECTS: Patients older
      than 60 years, admitted to a Veterans Affairs teaching hospital, and
      consecutively referred to a psychiatric consultation service for evaluation and
      treatment of a depressive disorder. METHODS: The diagnosis of delirium was based
      on two independent assessments: (1) a clinical interview by a member of the
      psychiatric consultation service and (2) a structured bedside evaluation
      performed by one of the investigators, who was not a member of the psychiatric
      consultation service. The investigator administered the Confusion Assessment
      Method Instrument, Mini-Mental State Examination, digit span forward, and months
      of year backward. The investigator also administered the Diagnostic Interview
      Schedule items for depression to elicit depressive symptoms. RESULTS: Twenty
      eight (41.8%) of the 67 subjects referred for evaluation or treatment of a
      depressive disorder were found to be delirious. Compared with nondelirious
      subjects, the delirious subjects were older and more impaired in activities of
      daily living. The delirious subjects often endorsed depressive symptoms, such as
      low mood (60%), worthlessness (68%), and frequent thoughts of death (52%). The
      referring health care provider had considered delirium in the differential
      diagnosis of the mood disturbance in only three subjects. CONCLUSION: Health care
      providers should consider the diagnosis of delirium in hospitalized elderly
      patients who appear to be depressed.

PMID- 7503606
TI  - Impact of marital status on outcomes in hospitalized patients. Evidence from an
      academic medical center.
AB  - BACKGROUND: Prior studies have described the importance of social support on long
      term patient outcomes. Few studies have investigated the impact of social support
      on outcomes in hospitalized patients. OBJECTIVE: To examine the relationship
      between marital status, an important aspect of social support, and several
      hospital outcomes. METHODS: Patients included 40,820 adult medical and surgical
      patients discharged from a midwestern academic medical center during 1988 through
      1991, of whom 21,291 were unmarried and 19,529 were married. Using multivariable
      regression analyses, we compared the following outcomes in married and unmarried
      patients: rate of in-hospital death, rate of nursing home discharge, length of
      stay, and hospital charges. Severity of illness was measured using a previously
      validated commercial method. RESULTS: Admission severity of illness was higher in
      unmarried than married patients; 40% of unmarried patients had moderate or high
      severity compared with 32% of married patients. In a series of multivariable
      analyses, controlling for severity of illness, age, gender, race, and diagnosis,
      the risk of nursing home discharge was more than 2.5 times greater for unmarried
      than for married patients (multivariable odds ratio, 2.67; 95% confidence
      interval, 2.33 to 3.06), while the risk of in-hospital death for unmarried
      compared with married patients was higher among surgical patients (odds ratio,
      1.30; 95% confidence interval, 1.06 to 1.58) but not among medical patients (odds
      ratio, 0.98; 95% confidence interval, 0.84 to 1.15). In additional analyses,
      multivariable models estimated that hospital charges and length of stay were 5%
      and 8% higher (P < .001), respectively, for unmarried than for married patients.
      In a series of stratified analyses, the above differences among unmarried
      patients tended to be greater for patients who were never married than for
      patients who were widowed, divorced, or separated. CONCLUSION: The findings
      suggest that marital status was an independent risk factor for several important
      hospital outcomes. This adds to our understanding of the importance of social
      support and other nonbiological factors on outcomes in hospitalized patients.
      This also has implications for the design of hospital-based interventions to
      improve patient outcomes and for the development of equitable prospective and
      capitated hospital payment formulas.

PMID- 7503608
TI  - 'Zamboni disease'. Pulmonary edema in an ice hockey player.
AB  - A 17-year-old previously well ice hockey player experienced acute shortness of
      breath and cough productive of clear frothy sputum about 1.5 hours following an
      ice hockey match. Noncardiogenic pulmonary edema was found to develop as a result
      of the inhalation of the oxides of nitrogen. The latter was produced by a Zamboni
      machine that is used to resurface the ice on a rink. Several other players were
      affected but less severely.

PMID- 7503607
TI  - Referral for dialysis in Ontario.
AB  - BACKGROUND: Because the incidence rates of treated end-stage renal disease are
      much lower in Canada than in the United States, we hypothesized that decisions,
      made by family physicians and community internists, not to refer certain patients
      to nephrologists might explain this difference. OBJECTIVE: To elicit patterns of
      practice and attitudes from nonnephrologist physicians who care for, and possibly
      refer, patients with renal disease. METHODS: A mailed survey was sent to a random
      sample of 1924 members of the Ontario Medical Association, Sections on General
      and Family Practice and Internal Medicine. Of 1778 eligible respondents,
      responses were received from 728 physicians (40.9%). RESULTS: Patients with
      microscopic hematuria (79.2%), proteinuria (69.5%), and serum creatinine levels
      in the 120 to 150 mumol/L (1.4 to 1.7 mg/dL) range (84.3%) were generally not
      referred by family physicians. A hypothetical question about patient age and
      comorbid features revealed that physicians were less likely to refer patients as
      their age and comorbidity increased. In response to the question, "In the past 3
      years, did you care for a patient who, after due consideration, died of renal
      failure without referral for dialysis," 14.2% of family physicians and 44.6% of
      internists said yes. Overall, 67.4% of respondents strongly or somewhat agree
      that rationing of dialysis is occurring now. Opinions about possible criteria for
      rationing of dialysis were that the majority strongly or somewhat agreed to
      basing a decision on the wishes of a competent patient (94.1%), short life
      expectancy (87.9), poor quality of life (87.0%), and age (63.6%). CONCLUSIONS:
      These results suggest that nonreferral for dialysis occurs in Ontario and that
      the act of referral, or nonreferral as the case may be, is influenced by both age
      and coexisting disease. The patterns of nonreferral reported raise a concern that
      patients who might benefit are not being referred to dialysis centers.

PMID- 7503609
TI  - Antithrombotic therapy in acute ischemic stroke.

PMID- 7503610
TI  - Response to DCCT: how sweet is it?

PMID- 7503611
TI  - Low cholesterol and violence.

PMID- 7503612
TI  - [Study of myocardial viability after recent infarction by echocardiography under
      dobutamine. Evidence of stunned myocardium].
AB  - After myocardial infarction treated by thrombolysis, secondary improvement of
      contractility may be observed due to the presence of viable but stunned
      myocardium in a zone of ischaemia. Echocardiography with lose dose Dobutamine has
      been proposed as a diagnostic test of myocardial viability. The inotropic effect
      of the pharmacological agent improves or induces myocardial thickening in zones
      of ischaemia. A positive response is observed in about one out of two cases. The
      sensitivity ranges from 79 to 86% and the specificity from 68 to 90% in the
      reported series. This mode of stress echocardiography for the study of post
      infarction myocardial viability is under clinical evaluation: its advantages and
      limitations should be compared with those of other non-invasive methods,
      especially thallium myocardial scintigraphy.

PMID- 7503613
TI  - [Indications of coronary angioplasty after thrombolysis].
AB  - Thrombolysis is the most widely used method of coronary reperfusion in the acute
      phase of myocardial infarction. The indications of angioplasty after thrombolysis
      have been subject of considerable controversy over the last few years. Three
      randomised trials (TIMI 2, TAMI, ECSG) have shown that it is not desirable to
      perform systematic immediate angioplasty after intravenous thrombolysis with rt
      PA. Angioplasty may be carried out as a "salvage" procedure in cases of failure
      of thrombolysis. The validity of this approach was confirmed recently by the
      "RESCUE" trial in anterior myocardial infarction. The practical application of
      its results is confronted by logistical problems inherent to the practice of
      angioplasty in the acute phase of myocardial infarction and to the inadequacy of
      non-invasive methods for the detection of coronary reperfusion after
      thrombolysis. Angioplasty may also be necessary in cases of left ventricular
      failure or cardiogenic shock. The efficacy of a rapid angioplasty in cases of
      recurrence of ischaemia after thrombolysis has been proved in reducing mortality
      and preserving left ventricular function. The results of TIMI IIB and SWIFT
      trials show that secondary angioplasty, several days after thrombolysis, is only
      usually indicated in patients with residual clinical ischaemia or positive stress
      tests. This attitude should however be modulated in the light of the "open
      artery" theory and the limitations of methods of evaluating myocardial viability.
      The present strategies will no doubt be modified with the introduction of new
      thrombolytic and/or antithrombotic agents and the use of coronary stents.

PMID- 7503614
TI  - [Lisinopril: myocardial infarction, the first 24 hours, in patients with stable
      hemodynamic status. The GISSI-3 study; results at 6 weeks].
AB  - The GISSI-3 study is a multicentre randomised trial, the aim of which is to
      assess the efficacy of lisinopril, of transdermic glyceryl trinitrate and their
      association on survival and left ventricular function after acute myocardial
      infarction. Between June 1991 and July 1993, 19,394 patients were randomised in
      200 Italian coronary care units. The patients were eligible if admitted within 24
      hours of the onset of symptoms, if they had a stable haemodynamic status and in
      the absence of contraindications to the study drugs. Using a factorial protocol,
      these patients were randomised to receive either oral lisinopril (5 mg/day as a
      starting dose followed by 5 mg at the 24th hour and then 10 mg/day) glyceryl
      trinitrate alone (intravenously for 24 hours followed by 10 mg by transdermic
      patch) or the association of the two drugs or neither (control group). The
      principal criteria were global mortality and a parameter of combined events. The
      combined parameter was defined as the number of deaths plus the number of late
      (after the 4th day of hospital admission) cases of clinical cardiac failure or of
      severe left ventricular dysfunction without clinical signs of cardiac failure.
      Complete clinical information and a six-week follow-up were obtained in 18,895
      (97.4%) of randomised patients. The global mortality at 6 weeks was 6.7%. The
      results of GISSI-3 show that treatment with lisinopril started (in addition to
      conventional therapy) in clinically stable patients during the first 24 hours of
      myocardial infarction and continued for 6 weeks significantly reduces (p = 0.03)
      global mortality at 6 weeks (6.3% in the lisinopril group versus 7.1% in the
      group without lisinopril), which results in 8 lives saved for every 1,000
      patients treated. This "gain in lives" is observed from the first day of
      treatment. At 6 weeks, the combined morbidity-mortality was 15.6% in the
      lisinopril group, compared with 17% in the group without lisinopril, a
      significant reduction of 8%. In patients receiving glyceryl trinitrate, the 6
      week mortality was 6.5% (617/9,453) compared with 6.9% (653/9,442) in the group
      not receiving this treatment; this difference was not significant. There was no
      significant difference in combined morbidity-mortality between these two groups
      (15.9 vs 16.7% respectively). The beneficial effect of lisinopril alone or
      associated with glyceryl trinitrate was also demonstrated on the combined
      parameter in high risk subgroups (elderly patients and women).(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7503615
TI  - [And after myocardial infarction?].

PMID- 7503616
TI  - [Which patients at risk of sudden death after myocardial infarction? Critical
      study of prognostic factors].
AB  - A lot of acquired data concerning the prognostic factors of post-infarction
      mortality dates from the pre-thrombolysis era. This mortality has considerably
      decreased since the active management of the acute phase of myocardial
      infarction. This has made it more complex to evaluate the post-infarction
      electrical risk and may have reduced the need. However, it is not less true that
      the assessment of the post-infarction risk necessitates a study of each factor
      predisposing to severe ventricular arrhythmias and sudden death: myocardial
      ischaemia, left ventricular dysfunction and electrical instability. The latter
      parameter may be assessed by non-invasive (ventricular extrasystoles, late
      ventricular potentials, heart rate variability, the baroreflex and the QT
      interval) and invasive methods (programmed ventricular stimulation). The
      association of these results has an excellent negative predictive value, and also
      improves the positive predictive value which, nevertheless, remains insufficient
      for expensive prophylactic measures associated with a certain morbidity, for
      example the implantation of a defibrillator device, to be taken.

PMID- 7503617
TI  - [Medical treatment after myocardial infarct: reflex prescription or thoughtful
      prescription].
AB  - There have been many therapeutic trials to determine the efficacy of given drugs
      prescribed after myocardial infarction. This may be explained by the very number
      of families of drugs which may intervene during the evolution of coronary artery
      disease. A common mistake is to think that the results of therapeutic trials can
      be automatically applied in clinical practice. In order for the demonstrated
      effect of a product to lead to its automatic prescription, there must be
      confirmation that the importance of the expected benefits does not depend on the
      type of infarction. This is probably the case for aspirin and the reduction of
      cholesterol levels which seem to be effective irrespective of the characteristics
      of the initial infarction. On the other hand, the efficacy or dangers of anti
      ischaemic drugs, angiotensin converting enzyme inhibitors or antiarrhythmics, is
      very dependent on the impact of the infarct on left ventricular function. The
      prescription of drugs after myocardial infarction depends on individual
      parameters which lead to the adaptation of consensus recommendations to each
      particular case.

PMID- 7503618
TI  - [Impact of controlling risk factors after myocardial infarction].
AB  - The relative risks of each factors and the benefits of their reduction after
      myocardial infarction are comparable to those observed in primary prevention.
      However, because of an overexposure to the risk, the absolute gains are five
      times greater. The impact of diet is one of the most important: in addition to
      the limitation of polyunsaturated fats and global calory intake, especially in
      cases of central obesity, the increase in dietary alpha-linolenic acid and in
      omega-3, has been shown to reduce the risk of myocardial infarction and mortality
      by up to 70%. Supplements of vitamins A and E could be useful. After infarction,
      the risks of an ex-smoker decrease rapidly by half and become comparable to those
      of non-smokers in 2 to 3 years. Physical exercise reduces cardiovascular
      mortality by 20-25% and contributes to better control of risk factors. The
      management of some psycho-physiological factors (reaction to stress, hostility)
      also gives encouraging results). A 10% reduction in total cholesterol leads to a
      20% or more decrease in coronary events and a 10% reduction in mortality with a
      marked dose-response effect inciting to the reduction of its level to under 2
      g/l. The progression of atherosclerosis delayed; early lesions, with the greatest
      risk of rupture and thrombosis, are stabilised and may even regress. A low HDL-c
      concentration should lead to more energetic reduction of LDL-c and control of
      smoking, obesity and sedentarity. Its association with hypertriglyceridaemia,
      glucose intolerance, hypertension and central obesity defines the syndrome of
      insulin resistance which multiplies cardiovascular risk.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7503619
TI  - Some issues concerning treatment in patients after myocardial infarction.

PMID- 7503620
TI  - [Calcium antagonists and primary prevention of coronary disease].
AB  - APSIS (Angina Prognosis Study in Stockholm) compared the effects of verapamil 480
      mg/day and metoprolol 200 mg/day on the prognosis of 809 patients with stable
      angina over an average period of three and a half years. No difference was
      observed between the two treatment groups in terms of mortality, number of
      cardiovascular events or in term of quality of life. Verapamil seemed to be as
      effective and as well tolerated as the betablocker for long term therapy of
      stable angina. Moreover, an ancillary study suggests that it has a platelet anti
      aggregant effect.

PMID- 7503621
TI  - [Post-infarction, myocardial ischemia: clinical importance and risk factor].
AB  - The myocardial scar, left behind by an infarct, makes up a potential substrate
      for complex ventricular arrhythmias due to the presence in such tissue of
      electrical inhomogeneity, altered refractoriness, and abnormal conduction
      properties, which facilitate the induction of reentrant arrhythmias and the
      release of abnormal automatic responses of the partially repolarised cells. The
      mechanism(s) by which complex ventricular arrhythmias is/are transformed into
      malignant arrhythmias has/have not yet been definitely proven. The observation
      that coronary revascularization - in patients with ischaemic heart disease
      surviving out of hospital cardiac arrest - improves the prognosis, indicates that
      transient ischaemic attacks might be the trigger of malignant ventricular
      arrhythmias in patients with prior myocardial infarction. Patients with large
      infarct scars (heart failure) have an increased incidence of complex ventricular
      arrhythmias, death, and ischaemic events. Antiarrhythmic medical intervention
      does not improve the prognosis in these patients. Intervention with ACE
      inhibitors reduces the prevalence of complex ventricular arrhythmias, the
      incidence of death, and reinfarction, but not arrhythmic death, indicating that
      residual ischaemia might be the major risk variable in patients with heart
      failure. Ischaemia is one of several risk markers for transient supraventricular
      arrhythmias in patients recovering from an acute myocardial infarction (AMI). In
      addition, anti-ischaemic intervention in patients recovering from AMI suppresses
      residual myocardial ischaemia and thereby reduces major events.

PMID- 7503622
TI  - [Calcium antagonists and prevention of post-angioplasty restenosis].
AB  - Five randomised double blind clinical trials have assessed the effects of long
      term therapy with calcium antagonists on post-coronary angioplasty restenosis.
      Nifedipine 40 mg/day was tested in 241 patients by Whitworth et al: there was no
      difference in the incidence of restenosis between the treatment and placebo
      groups. Corcos et al studied the effects of diltiazem 270 mg/day in 92 patients:
      there was no significant difference between the two groups. In a study of 201
      patients, O'Keefe et al found no significant difference in incidence of
      restenosis in a group treated with diltiazem (240 to 360 mg/day) compared with
      placebo. The fourth trial, conducted by Unverdorben et al, not yet fully
      published, in 170 patients, showed a significant reduction in restenosis in
      patients treated with diltiazem 180 mg/day (p = 0.03). Finally, the VAS trial
      (Verapamil Angioplasty Study) showed high dose verapamil (480 mg/day) to reduce
      the incidence of restenosis in a subgroup of patients with stable angina and high
      risk of restenosis.

PMID- 7503623
TI  - [Calcium antagonists in cardiovascular diseases].
AB  - By blocking the inward transmembrane calcium current and opposing the effects of
      increased intracellular ionised calcium, calcium antagonists exert vascular and
      myocardial effects which are useful therapeutic tools. Coronary and peripheral
      vascular relaxation results in an increase in coronary flow and a reduction of
      the afterload and, therefore, of myocardial oxygen consumption. In some cases,
      negative myocardial inotropic and chronotropic effects also reduce myocardial
      oxygen requirements. Spastic angina is the indication of choice of all calcium
      antagonists whereas, to date, verapamil and diltiazem have been shown to be
      effective in stable angina and, in the post-infarction situation, diltiazem and
      verapamil decrease the number of cardiovascular events, and verapamil alone has
      been shown to reduce mortality. All calcium antagonists have been shown to be
      effective in hypertension and most have a protective effect on the target organs.
      The main fields of research concern atherosclerosis, the primary prevention of
      myocardial infarction and the study of molecules which can be used in heart
      failure.

PMID- 7503624
TI  - Discovery, mechanism and expected clinical significance of selective cytotoxicity
      of 2-chloro-2'-deoxyadenosine (2-CdA).
AB  - 2-Chloro-2'-deoxyadenosine (2-CdA) is a new promising antileukemic and
      immusuppressive agent. Discovery of 2-CdA and its unique properties, methods of
      synthesis, data explaining mechanism of its selective cytotoxicity, and current
      clinical status of the drug are briefly reviewed.

PMID- 7503625
TI  - Antileukemic and Immunosuppressive Properties of 2-Chloro-2'-Deoxyadenosine (2
      CdA). Symposium proceedings. Warsaw, Poland, November 23, 1992.

PMID- 7503626
TI  - Cladribine (2-chloro-2'-deoxyadenosine): new perspectives in clinical
      immunosuppression.
AB  - Cladribine (2-chloro-2'-deoxyadenosine) has been recently introduced in the
      treatment of hematologic malignancies. We have shown that CdA has potent
      inhibitory activity in vitro and in vivo in concentrations readily achievable in
      the sera of treated patients. The immunosuppressive efficacy of CdA was at least
      equal to that of cyclosporine. Furthermore, CdA is particularly efficacious
      inhibitor of B cell activation.

PMID- 7503627
TI  - Stability of 2-chloro-2'-deoxyadenosine at various pH and temperature.
AB  - In this paper data concerning the stability of 2-chloro-2'-deoxyadenosine (2-CdA)
      solutions at various pH and temperature conditions are presented. Decomposition
      of 2-CdA was measured as content of its hydrolysis product--2-chloroadenine,
      using the HPLC method. We found that 2-CdA is stable at basic and neutral pH and
      temperatures between 37 and 80 degrees C. At acidic pH, decomposition markedly
      increased with time, even in physiological temperatures. At pH 2 and 37 degrees,
      after 6 h, only 13% of 2-CdA remained in solution. At pH 1--after 2 h of heating
      to 37 degrees 2-CdA content was as low as 2%. Calculated half time T 1/2 was
      equal to 1.6 h (pH 2, temperature = 37 degrees) and 0.37 h (pH 1, temperature =
      37 degrees).

PMID- 7503628
TI  - Apoptotic death of lymphocytes upon treatment with 2-chloro-2'-deoxyadenosine (2
      CdA).
AB  - In this work we addressed the question if the difference in the mechanism by
      which 2-CdA kills resting and proliferating cells could be responsible for the
      therapeutic window of the drug. We show that 2-CdA triggers programmed cell death
      in proliferating human promyelocytic cell line, HL-60, human lymphocytic cell
      line, MOLT-4, and human peripheral blood lymphocytes stimulated to proliferation
      by PHA. Under our experimental conditions 2-CdA failed to induce apoptosis in the
      resting human peripheral blood lymphocytes despite induction of massive apoptosis
      in the same lymphocytes stimulated to proliferation by PHA. We also show that 2
      CdA-induced apoptosis in HL-60 and MOLT-4 cells can not be prevented by addition
      of nicotinamide or inhibiting poly(ADP-ribose) synthetase by 3-aminobenzamide. In
      the case of HL-60 cells apoptosis is specific to the S phase of the cell cycle.
      Taking together these data suggest that selective induction of apoptosis in
      proliferating cells may be responsible for the therapeutic value of 2-CdA.

PMID- 7503629
TI  - Treatment of patients with hairy cell leukemia with 2-chloro-2'-deoxyadenosine (2
      CdA).
AB  - Six patients with hairy cell leukemia have been treated with 2-chloro-2'
      deoxyadenosine in a dose 0.05 mg/kg/daily in 2 h intravenous infusions during 7
      consecutive days. Two patients underwent splenectomy with no clinical or
      hematologic improvement. Complete remission has been achieved in 4 patients and
      partial remission in one. 2-CdA was not effective in a patient with HCL-variant.
      The longest unmaintained CR lasted 11 months. The drug was well tolerated. Only
      slight side effects were observed. The drug exerted, however, myelosuppressive
      action resulting in cytopenias in the peripheral blood. Clinical consequences of
      this activity require further investigation. 2-CdA seems to be a drug of choice
      in the management of HCL.

PMID- 7503630
TI  - Treatment of hairy cell leukemia patients with 2-chloro-2'-deoxyadenosine (2
      CdA).
AB  - A preliminary study of six hairy cell leukemia patients treated with one course
      of 2-chloro-2'-deoxyadenosine (2-CdA) is presented. 2-CdA was administered 0.1
      mg/kg/daily by intravenous infusion over 7 days. Two patients achieved CR and
      four PR.

PMID- 7503631
TI  - Systemic administration of 2-chloro-2'-deoxyadenosine (2-CdA) in patients with
      systemic scleroderma.
AB  - Three patients with diffuse variety of systemic scleroderma were treated with 2
      chloro-2'-deoxyadenosine. In two of them a moderate improvement of skin
      involvement was observed. No significant effects of the drug on the immunological
      parameters have been found.

PMID- 7503632
TI  - 2-Chloro-2'-deoxyadenosine (2-CdA) treatment in a patient with Waldenstrom's
      macroglobulinaemia complicated by severe neutrocytopenia.
AB  - A 68-year-old male patient with newly diagnosed Waldenstrom's macroglobulinaemia
      complicated by severe neutrocytopenia at presentation of the disease was treated
      with 2-CdA. Partial remission with an increase in neutrocyte count was achieved.

PMID- 7503633
TI  - Influence of 2-chloro-2'-deoxyadenosine alone and in combination with
      cyclophosphamide or methotrexate on murine leukemia L1210.
AB  - The influence of 2-CdA administrated alone and in combination with CY or MTX on
      the survival time of mice bearing L1210 leukemia was investigated. 2-CdA treated
      mice lived longer than control animals. Survival times of mice receiving combined
      therapy of 2-CdA and CY were significantly prolonged as compared with mice
      treated with these agents separately. Survival times of mice treated with 2-CdA
      and MTX were not significantly prolonged, compared with animals receiving 2-CdA
      alone.

PMID- 7503634
TI  - 2-Chloro-2'-deoxyadenosine (2-CdA) combined with cyclosporine A successfully
      prevents rejection of fetal brain stem allograft in rabbits.
AB  - Allografts of brain stem from 20-day-old fetuses to nucleus caudatus of adult
      rabbits were performed. To prevent graft rejection immunosuppression with 2-CdA
      and cyclosporine A was transiently induced. Graft survival were assessed by
      histological and electrophysiological techniques. Both morphological
      (synaptogenesis, myelinization) and functional (generation of rhythmic neuronal
      activity) signs of graft maturation were found after nine weeks. The data suggest
      that transient immunosuppression used is sufficient to induce tolerance to neural
      graft, and no interference with maturation of implanted fetal tissue occurs.

PMID- 7503635
TI  - Modulation of lymphocyte-fibroblast interactions by 2-chloro-2'-deoxyadenosine (2
      CdA) in subarachnoid hemorrhage.
AB  - The adherence to monolayers of human fibroblasts of chromium-51 labelled
      peripheral blood mononuclear cells (PBMC) from normal subjects, and from patients
      after single or multiple subarachnoid hemorrhage (SAH), and the effect of 2-CdA
      on cell adhesion have been quantified. The fraction of cells adhering to
      fibroblasts were the lowest for multiple SAH patients and the highest for normal
      subjects, which can be explained by depletion of activated lymphocytes from
      peripheral blood of SAH patients. 2-CdA decreased the fraction of adhering cells
      isolated from normal subjects, did not change the adherence of cells from single
      SAH patients and increased the fraction of adhering cells isolated from multiple
      SAH patients. We conclude that the influence of 2-CdA on the adherence of PBMC to
      fibroblasts is inversely related to the degree of immune system activation.

PMID- 7503636
TI  - Comparative evaluation of toxicity and antitumor activity of original and
      reproduced anthracycline drugs.
AB  - Two anthracycline drugs--doxorubicin and 4'-epidoxorubicin--synthesized at the
      Institute of Biotechnology and Antibiotics were tested in vivo for their
      biological activity in comparison with original Farmitalia drugs. In parallel
      experiments similar properties of both drugs and referentials were displayed:
      comparable subacute and delayed toxicity from i.p. and i.v. routes of
      administration as well as antitumor effectiveness in two mouse transplantable
      tumor models--P388 leukemia and B16 melanoma. No statistically significant
      differences between reproduced and original drugs were found.

PMID- 7503638
TI  - Standardization of HeLa cells preparations as the source of snRNA's for
      preliminary study on the effectors of pre-mRNA splicing.
AB  - Physical, chemical and biological parameters of HeLa cell cultures, which ensure
      obtaining standard nuclear material to be used as a source of snRNP and snRNA,
      have been determined. The secondary structure of U1 snRNA as the result of the
      conformational studies performed using S1 nuclease, A and T1 ribonuclease and
      Pb(II) ions, and reproducibility of the results obtained after 6-48 h exposure of
      the cells to actinomycin D at high concentration permit to accept the proposed
      method of standardization as satisfactory for investigation into snRNP and snRNA.

PMID- 7503637
TI  - Immunosuppressive and cytogenetic effects of pelvic irradiation on the peripheral
      lymphocytes of patients with cervical cancer. One year follow-up.
AB  - The circulating lymphocytes of patients treated for cervical cancer were examined
      by four independent manners: by evaluation of T-cell proportion in peripheral
      blood, proliferative response upon PHA stimulation, PHA-induced leukocyte
      migration inhibition, and by concomitant chromosome aberration frequency. The
      immediate and longer-term effects of pelvic irradiation on T lymphocytes were
      investigated in 19 patients prior to, during, and immediately after radiotherapy,
      and then at subsequent intervals of two, three and five months. Radiotherapy
      caused profound depression of already diminished T-cell number and their
      proliferative response; both parameters gradually recovered during post-treatment
      period, and achieved their pretreatment values at the end of follow-up. The
      leukocyte migration inhibition was much less affected; it slightly deteriorated
      in the middle of post-treatment period, but reached the pretreatment level at the
      end of monitoring. The chromosome aberration frequency increased during
      irradiation in dose-dependent manner; it decreased gradually thereafter, but
      remained high during follow-up. Their elimination rate correlated with the
      recovery of T-cell number and proliferative response. However, at the end of
      monitoring, when all immunological parameters were completely recovered from
      harmful effect of irradiation, the percentage of chromosome aberrations remained
      high (12.5%), although significantly lower than the post-treatment one.

PMID- 7503640
TI  - Heparin enhances generation of natural killer activity in vitro.
AB  - The effect of heparin on generation and activity of NK cells in vitro were
      studied. Heparin decreased NK cytotoxicity when present in the assay. In
      contrast, the agent increased generation of NK cytotoxicity and showed
      synergistic action with recombinant IL2.

PMID- 7503639
TI  - 2-Chloro-2'-deoxyadenosine--clinical, biochemical and pharmacokinetic
      considerations.
AB  - 2-Chloro-2'-deoxyadenosine (CdA) is a new antimetabolite with very promising
      effect in the treatment of chronic lymphoproliferative diseases. It has also been
      shown to have good activity in acute myelogenous leukemia in children. CdA
      induces DNA single strand breaks and poly(ADP)-ribosylation, apoptosis and is
      cytotoxic to non-proliferating as well as proliferating cells. Earlier, CdA has
      only been given as continuous infusion. Recently, however, pharmacokinetic
      studies have shown that the bioavailability of oral CdA is 50% and of s.c.
      injection 100%. Furthermore, studies of the intracellular pharmacokinetics shows
      that there is a prolonged retention of its nucleotide metabolites supporting
      intermittent dosing.

PMID- 7503641
TI  - In vitro primary antitumor screen of imidazole platinum complexes.
AB  - The cytostatic activity in vitro of six cis-platinum analogs with imidazole
      ligands was examined. The tests were performed on 60 lines of human neoplastic
      cells in the NCI Preclinical Antitumor Drug Screening Program. The results
      obtained from 10 the most sensitive lines were analyzed and the structure
      activity relationship was deduced. The cytotoxic activity of the active complexes
      seems to correlate with the hydrophobic properties of neutral imidazole ligands
      and with kinetic properties of anionic ligands.

PMID- 7503642
TI  - The reduced expression of HLA-class II antigens and adhesion molecules on
      monocyte surface after phagocytosis of bacteria.
AB  - The reduced expression of HLA-class II antigens (DQ and DP) and some
      intercellular adhesion molecules (CD11b, CD54 and CD58) was found on monocytes
      after phagocytosis of bacteria (S. aureus, E. coli, P. aeruginosa, S.
      enteritidis) but not of latex particles. In contrast, the expression of HLA-DR,
      CD11a and CD18 was not changed in the course of phagocytosis. The observed
      changes were related to the amount of phagocytosed bacteria but not to their
      viability or phagocytosis induced physical changes expressed as the reduction of
      FSC signal during flow cytometry analysis.

PMID- 7503643
TI  - Kinetics of distribution of recirculating lymphocytes during whole body
      hyperthermia.
AB  - Whole body hyperthermia (WBH) not only embraces lymphocyte migration to the bone
      marrow and skin, but also prolongs their subsequent transit through these organs,
      while inhibiting homing to the lymphoid organs. The effect of WBH is transitory,
      it subsides within 16 h after a 8 h WBH period. The accumulation of circulating
      lymphocytes in lymph nodes, Payer's patches and spleen dropped significantly
      between 4 h and 8 h in WBH, but rose during subsequent 16 h normothermia. In the
      absence of the adrenal glands, the enhanced bone marrow localization observed in
      non-adrenalectomised rats during WBH did not occur. Skin localization increased
      while splenic localization fell in adrenalectomised as compared to non
      adrenalectomised rats. These results strongly support the hypothesis that WBH
      induced enhancement of lymphocyte migration to the bone marrow is adrenal-hormone
      dependent. The above mentioned changes can not be attributed to changes in blood
      flow to the tissues during WBH. Blood flow to the bone marrow was not
      significantly different from flow to this organ in normothermic rats. Flow to the
      skin fell significantly and yet localization in this tissue during WBH was higher
      than during normothermia.

PMID- 7503644
TI  - Presentation of antigen by B cells subsets. I. Lyb-5+ and Lyb-5- B cells differ
      in ability to stimulate antigen specific T cells.
AB  - We have examined the antigen presenting cell (APC) function of different B cells.
      Resident, peritoneal B cells from normal mice were more efficient than splenic B
      cells in presenting antigen to CD4+ T cell lines. Peritoneal B cells from X
      linked immunodeficient (Xid) mice, by contrast, stimulated no detectable
      responses. Xid splenic B cells were much less efficient APC than normal splenic B
      cells. B cells from neonatal mice also were very poor APC until the mice were 3
      to 4 weeks old. Xid B cells presented antigen to T cell hybridomas as well as
      normal B cells showing that they process antigen normally. Thus, the defect is
      most likely in providing secondary signals. The ability of B cells to present
      antigen efficiently correlates with the percentage of B cells reported to express
      the Lyb-5 antigen. Anti-Lyb-5 serum and complement abrogated the APC activity of
      B cells suggesting that Lyb-5+, but not Lyb-5- cells are efficient APC. We also
      found that activated and resting normal splenic B cells, separated by buoyant
      density, presented antigen equally. Both populations also contained Lyb-5+ B
      cells although they were a larger fraction of the activated cells. Lyb-5 is now
      thought to be an activation antigen rather than a differentiation antigen. If
      this idea is correct, then our data indicate that anti-Lyb-5 more cleanly
      separates activated and resting B cells than buoyant density techniques.

PMID- 7503645
TI  - Study on the role of urine gamma-glutamyl transpeptidase activity during
      investigation of nephrotoxicity.
AB  - In this study, gamma-glutamyl transpeptidase activities of the 24 h urine samples
      taken at the end of the fourth day from the rats to which 160 mg/kg/day
      gentamicin was applied i.p. for 4 days, were measured. Glucose determination in
      urine by the use of the glucose hexokinase method was also applied in order to
      control the reabsorption potentials of the tubules. The formation of necrosis in
      the kidneys was investigated by histological examinations of the damage occurred
      by the nephrotoxic effect. All the results were compared with the values obtained
      from the control group. The average gamma-glutamyl transpeptidase activity for
      the control group (n = 22) was determined as 5.68 +/- 0.26 IU/24 h whereas this
      level was detected as 15.6 +/- 1.0 IU/24 h in the drug applied group (n = 15).
      The measurement of gamma-glutamyl transpeptidase activity in urine can be applied
      as a useful parameter on determination of nephrotoxicity, especially for
      indicating the dimensions of this toxic effect.

PMID- 7503646
TI  - Chemiluminescence immunosorbent assay (CLISA) and a possibility of the specific
      detection of soluble antigens of Clostridium botulinum type A.
AB  - A double antibody version of CLISA was demonstrated to be a rapid method (1 h)
      for detection and quantitative determination of Clostridium botulinum toxin
      antigens in biological samples. The sensitivity of this assay is about ten-fold
      higher than both ELISA and passive hemagglutination test. Thus, the double
      antibody version of CLISA appeared to be useful for the control of food products
      contaminated with Cl. botulinum type A bacteria.

PMID- 7503647
TI  - Effect of pretreatment of wells in polystyrene plates on adsorption of some human
      serum proteins.
AB  - Coating of Immulon polystyrene plates with 0.2% casein in phosphate buffered
      saline (PBS) completely abolishes adsorption of human serum proteins to these
      plates. However, pretreatment of such plates with PBS or 0.15 M NaCl in deionized
      water (10 microS) before coating makes possible adsorption of human
      immunoglobulins G (HIgG) and M but not serum albumin (HSA) and transferrin
      (HTrf). Effect of pretreatment with PBS on adsorption of HIgG is long-term and
      rather stable. Results of experiments with radioiodinated HIgG, mouse IgG, HSA
      and human chorionic gonadotropin confirm the peculiar effect of pretreatment with
      PBS on casein coating. Pretreatment with deionized water, instead of PBS,
      markedly diminish adsorption but tap or commercial spring waters (> 1000 microS),
      even without 0.15 M NaCl, affect adsorption similarly to PBS in deionized water.
      Super pure water (0.05 microS) even with NaCl used for pretreatment does not
      influence adsorption of HIgG to plates coated with casein. Distinct differences
      in adsorption of HIgG and HTrf was demonstrated using solutions for ELISA
      prepared from super pure, deionized and tap waters.

PMID- 7503648
TI  - Studies on transplantation immunity of the yellow-bellied toad Bombina variegata.
AB  - Adults and tadpoles of the yellow-bellied toad Bombina variegata reacted in a
      typically chronic manner to skin allografts and to xenografts from closely
      related fire-bellied toads B. bombina but they rejected quickly skin xenografts
      from evolutionary distant anuran species (Bufo and Rana). Adult individuals
      reacted to allografts slowly not only in the laboratory where their mating was
      ceased and the weight of lymphoid organs significantly diminished but also in the
      outdoor enclosure where they bred successfully. Breeding activity in captivity
      can be induced at any season by Biogonadyl injections. However, any hormonal
      manipulation (gonadectomy or Biogonadyl treatment) performed during winter/spring
      on animals housed in the laboratory for several months did not influence their
      transplantation immunity and the weights of thymuses and spleens. These results
      lead to conclusion that chronic allograft rejection was not a laboratory artifact
      caused by a hormonal imbalance but rather reflected a weak donor-host genetic
      disparity connected with the low MHC polymorphism of Bombina species.

PMID- 7503649
TI  - Immunotropic activity of lupin seeds extracts and fractions from Lupinus
      angustifolius and Lupinus albus.
AB  - The results demonstrated immunotropic activity of seeds extracts and fractions
      from Lupinus angustifolius and Lupinus albus. Plaque forming cells (PFC) number
      to SRBC (sheep red blood cells) were elevated by an extract from Lupinus
      angustifolius and lowered by extracts from Lupinus albus. All preparations
      obtained from Lupinus angustifolius reduced the number of rosette forming cells
      (E-RFC). These preparations suppressed also the intensity of graft versus host
      reaction (GVHR) in case when the donors were treated. Lupinus albus extract
      suppressed GVH reaction when recipients were treated. Lupin extracts stimulated
      draining popliteal lymph nodes in PLN assay.

PMID- 7503650
TI  - Mechanism of antigenic variation in Shigella flexneri. II. Sensitivity to
      complement as a selection factor for antigenic mutant 3b in 1b serotype.
AB  - In the first report we stated that the antigenic mutant of Shigella flexneri 6713
      3b serovar with antigenic formula III: 3, 4, 6 was less sensitive to bactericidal
      action of normal calf serum in comparison to its parent strain S. flexneri 6713
      1b with antigenic formula III: 3, 4, 6. In this paper we show that the phenomenon
      is rather a general one; the difference in sensitivity was observed in three
      other strains S. flexneri 1b of independent clinical origin and its antigenic
      mutants 3b respectively. As the result of serial treatment of these strain with
      the serum among the survivors the antigenic mutants have been found. In the
      artificial mixtures of the mutants and isogenic original strains treated with the
      serum the later show clear cut higher survival.

PMID- 7503651
TI  - Molecular mimicry between Fc receptors and viral antigens.
AB  - Molecular mimicry has been characterized as the presence of common epitopes,
      either linear or conformational, shared by host and microbial determinants. Such
      cross-reactivity may lead to an autoimmune disease. On the other hand molecular
      mimicry between certain viral proteins and host determinant may protect invading
      virus to be eliminated by immune system and may promote persistence. In this mini
      review I discuss the molecular mimicry of S peplomer protein of mouse hepatitis
      virus, strain JHM (MHV-JHM) to the host Fc gamma receptor (Fc gamma R). MHV-JHM
      induces in rodents acute encephalomyelitis and surviving animals develop
      demyelinating disease with concomitant persistent infection. We have demonstrated
      that rabbit IgG, but not is F(ab')2 fragments, monoclonal rat and mouse IgG and
      the rat 2.4G2 anti-Fc gamma R mab immunoprecipitated natural and recombinant S
      peplomer protein of several strains of MHV. Furthermore, MHV-JHM infected cells
      formed rosettes with anti-sheep red blood cell (SRBC) - antibody coated SRBC. The
      2.4G2 anti-Fc gamma R mab are able to neutralize several strains of MHV,
      presumably by binding to S peplomer protein. Therefore, the Fc binding site of S
      is present on the surface of MHV-infected cells. This molecular mimicry between S
      peplomer protein of MHV-JHM and Fc gamma R has been extended to other members of
      Coronaviridae, namely bovine coronavirus and transmissible gastroenteritis virus
      but not to infectious bronchitis virus. The molecular mimicry of viral antigens
      to Fc receptors has been described also for members of Herpesviridae, namely
      Herpes simplex, cytomegalovirus and Varicella zoster.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7503652
TI  - Tubulovesicular structures (TVS): virus-like particles specific for all subacute
      spongiform virus encephalopathies--what are they really?
AB  - Tubulovesicular structures (TVS) are virus-like particles specific for all the
      subacute spongiform virus encephalopathies (SSVE). I report here the presence of
      TVS in the highest range of naturally occurring and experimentally induced SSVE
      studied so far: natural and experimental Creutzfeld-Jakob disease (CJD),
      Gerstmann-Straussler-Scheinker syndrome, natural bovine spongiform encephalopathy
      (BSE) and BSE transmitted to pigs and four models of experimental scrapie in
      hamsters. TVS are spherical particles, approximately 30 nm in diameter. They are
      observed at both sides of synaptic cleft (i.e. in dendrites and axonal
      preterminals and terminals). By the ultrastructural criteria, TVS are easily
      differentiated from other spherical or tubular elements of the nervous system:
      microtubules, synaptic vesicles, multivesicular bodies and glycogen granules. The
      number of affected processes roughly correlates with infectivity titre. Their
      significance is unknown!

PMID- 7503653
TI  - An improved experimental model for the study of in vitro release of nitric oxide
      by murine peritoneal macrophages.
AB  - In the immune system macrophages are the cells responsible for nitric oxide (NO)
      production. The synthesis of NO by activated macrophages correlates with their
      cytotoxic effect on neoplastic cells as well as killing of intracellular
      parasites. In the present paper we test several parameters that may influence (in
      vitro) NO production by murine peritoneal macrophages previously stimulated in
      vivo by intraperitoneal injection of thioglycollate. In our system the maximum
      NO/NO2- release was obtained in the culture containing 10(6) M phi/ml after 24 h
      incubation. For macrophage activation we used lipopolysaccharide (LPS) and
      several recombinant cytokines (IFN-gamma, TNF-alpha, IL-2, IL-3, IL-6). We also
      tested the influence of latex phagocytosis on NO production by simultaneously
      activated macrophages.

PMID- 7503654
TI  - Organ-limited autopsies: obtaining permission for postmortem examination of the
      urinary tract.

PMID- 7503655
TI  - The autopsy and the public need.

PMID- 7503656
TI  - Rescreening in gynecologic cytology. Rescreening of 3762 previous cases for
      current high-grade squamous intraepithelial lesions and carcinoma--a College of
      American Pathologists Q-Probes study of 312 institutions.
AB  - OBJECTIVE: To quantitate, characterize, and analyze errors identified in the
      rescreening of previous gynecologic cytology specimens with original diagnoses of
      "within normal limits" or "benign cellular changes" for current cases diagnosed
      as carcinoma or high-grade squamous intraepithelial lesion. DESIGN AND SETTING:
      College of American Pathologists Q-Probes laboratory quality improvement study in
      312 laboratories. MAIN OUTCOME MEASURE: False-negative rate in cases rescreened
      as a result of a current cytologic diagnosis of carcinoma or high-grade squamous
      intraepithelial lesion. RESULTS: During the examination and reporting of
      1,741,515 current Papanicolaou smear cases, participating laboratories rescreened
      a total of 3762 previous cases that were originally diagnosed, during the 5 years
      prior to the current case, as being within normal limits or having benign
      cellular changes. For the rescreened cases, the overall false-negative rates were
      10.1% using a narrow definition and 19.7% using a broad definition. The majority
      of errors for cases originally diagnosed as within normal limits were screening
      errors, while interpretive errors predominated in those cases originally
      diagnosed as having benign cellular changes. Eighty-six percent of all false
      negatives were identified in those previous cases that were originally diagnosed
      and reported in the 3 years prior to the current case. CONCLUSIONS: Rescreening
      of previously reported smears, in patients with current abnormal findings, as one
      component of a complete quality improvement program, identifies errors that may
      provide information that will enable a laboratory to improve future performance.

PMID- 7503657
TI  - Production, analysis, and characterization of reference materials for prostate
      specific antigen.
AB  - OBJECTIVE: To produce a set of three reference materials that mimic sera from
      patients with prostate disorders in the prostate-specific antigen (PSA)
      concentration range important for clinical screening for prostate cancer
      (approximately 0.5, approximately 4.0, and approximately 10.0 ng/mL), to analyze
      these reference materials in a large number of clinical laboratories using a
      variety of commercially available methods, and to characterize the molecular
      forms of PSA in them. METHODS: Units of serum from healthy individuals and from
      patients with varying degrees of elevated PSA were pooled, lyophilized, and
      distributed along with conventionally prepared, semen-supplemented proficiency
      testing samples to laboratories participating in the College of American
      Pathologists Basic Ligand Survey. The reference material and one of the standard
      Survey samples were fractionated by Sephacryl S-200-HR gel filtration
      chromatography. RESULTS: The Abbott IMx, Hybritech Tandem-E, Hybritech Tandem-R,
      and Tosoh AIA-Pack all measured PSA in the reference material fairly equally
      (agreement within +/- 12%). In contrast, the Abbott IMx results in the semen
      supplemented Survey specimens were as much as 1.8-fold higher than the other
      three assays. Characterization of the molecular forms showed the reference
      material was approximately 90% alpha 1-antichymotrypsin-bound PSA, whereas the
      semen-supplemented Survey specimens were approximately 40% alpha 1
      antichymotrypsin-bound PSA, which largely explained the difference in assay
      recoveries. CONCLUSIONS: Semen-free materials containing only endogenous PSA much
      more closely mimic real clinical specimens and should prove useful in efforts to
      standardize clinical PSA assays.

PMID- 7503658
TI  - College of American Pathologists Conference XXVI on clinical relevance of
      prognostic markers in solid tumors. Summary. Members of the Cancer Committee.

PMID- 7503659
TI  - College of American Pathologists Conference XXVI on clinical relevance of
      prognostic markers in solid tumors. Report of the Colorectal Cancer Working
      Group.
AB  - The College of American Pathologists Conference XXVI in June 1994 was devoted to
      a discussion of the clinical relevance of prognostic factors in three solid
      tumors (breast, prostate, and colorectal). The group considering prognostic
      factors for adenocarcinoma of the large gut consisted of 15 pathologists,
      investigators, and surgeons. The group concluded that only a few items are well
      supported in the existing literature and can be recommended for routine clinical
      use at this time (pathologic TNM information and stage, tumor type, tumor grade,
      extramural venous invasion, and preoperative serum carcinoembryonic antigen
      level). According to the classification system used at the conference, these
      markers warrant categorization as important prognostic factors (category I). A
      few factors should be considered as potentially useful after further study
      (category II). Furthermore, the group agreed that all other current measurements
      of so-called prognostic factors do not warrant the same recognition of
      importance, either because they have been studied insufficiently or studies have
      demonstrated that they do not contribute to prognostication. These additional
      items were placed in category III. It was also concluded that the statistical
      methods used to identify and validate prognostic markers, as well as their
      integration into single statements of prognosis need further national evaluation
      and standardization.

PMID- 7503660
TI  - College of American Pathologists Conference XXVI on clinical relevance of
      prognostic markers in solid tumors. Report of the Prostate Cancer Working Group.
AB  - Critical analysis of the evidence supporting the use of prognostic markers is
      needed for these to be used most appropriately in patient management. The College
      of American Pathologists recently sponsored a national conference to review the
      status of tumor markers for carcinomas of the breast, colon, and prostate gland.
      The conclusions of the Prostate Cancer Working Group are presented in this
      report. Currently, the TNM (Tumor, Lymph Node, Metastasis) staging system,
      histologic grading (Gleason system), and serum prostate-specific antigen are
      recommended for general use as prognostic markers in prostate cancer. Data
      support the use of DNA ploidy analysis in specific clinical settings, although
      general use is not currently recommended. The Working Group concluded that other
      markers do not have sufficient support in the literature to recommend routine use
      at the present time.

PMID- 7503661
TI  - Accurate direct determination of low-density lipoprotein cholesterol using an
      immunoseparation reagent and enzymatic cholesterol assay.
AB  - Clinical laboratories currently estimate low-density lipoprotein cholesterol
      using the Friedewald formula, which requires fasting specimens and is subject to
      error with increasing triglyceride levels. We describe a rapid method for
      isolating low-density lipoproteins using the Direct LDL Immunoseparation Reagent
      for subsequent measurement of cholesterol by conventional assay. This method
      meets current guidelines for precision with within-run and run-to-run
      coefficients of variation of less than 3%. Results are in good agreement with the
      beta quantification reference method (Direct LDL-C = 1.03 [beta quantification] 
      0.06 mmol/L, [2.4 mg/dL] r = 0.980), there is minimal bias associated with
      increasing triglycerides or high-density lipoprotein cholesterol, and patient
      fasting is not required for accurate analysis. The Direct LDL Immunoseparation
      Reagent overcomes drawbacks of the Friedewald formula and appears to be suitable
      for accurate quantitation of low-density lipoprotein cholesterol in the routine
      laboratory.

PMID- 7503662
TI  - The diagnostic value of thrombomodulin immunolocalization in serous effusions.
AB  - OBJECTIVE: To test the value of an antithrombomodulin monoclonal antibody as a
      diagnostic tool in detecting mesothelial cells and in differentiating
      mesothelioma from other malignant effusions. DESIGN: Thrombomodulin is a thrombin
      receptor that is distributed on surfaces where an anticoagulant activity is
      expected, including mesothelium. Antigen expression was studied by
      immunocytochemistry in 226 peritoneal and pleural exudates. RESULTS: The antigen
      was found in 33 of 33 mesotheliomas, 35 of 35 reactive effusions, 57 of 145
      carcinomatous fluids, and in one case of angiosarcoma among seven metastatic
      nonepithelial tumors. Three distinct staining patterns were demonstrated: (1)
      thin cell membranes in benign mesothelial cells; (2) thick cell membranes in
      mesotheliomas; and (3) cytoplasm in carcinomas. All squamous cell carcinomas had
      demonstrable thrombomodulin, suggesting that antigen expression likely correlates
      with squamous differentiation. CONCLUSIONS: Thrombomodulin is of diagnostic
      utility in distinguishing mesothelioma from adenocarcinoma, provided the
      characteristic "thick membrane" pattern is present, but it should be used in
      panels with other markers of mesothelial and/or epithelial differentiation.

PMID- 7503663
TI  - Laboratory evaluation of the Miles H.3 automated reticulocyte counter. A
      comparative study with manual reference method and Sysmex R-1000.
AB  - OBJECTIVE: To evaluate the performance of the new commercial Miles H.3 RTX
      analyzer in counting reticulocytes. METHODS AND PATIENTS: The results from the
      counter were compared to those obtained from microscopic methods, following the
      National Committee for Clinical Laboratory Standards H44-P guidelines, and to the
      results from the Sysmex R-1000 counter. In total, 279 samples were analyzed in
      duplicate with each of the three methods. One hundred thirty-three samples were
      from healthy subjects, while 146 were from patients with various pathologies, 10
      of whom presented with posttherapeutic aplasia of the bone marrow and 9 with iron
      deficiency anemia. RESULTS: The reference intervals for the normal controls are
      different for each of the three methods (manual: 0.35-2.35%, 16 to 116 x 10(9)/L;
      Miles H.3: 0.65-2.30%, 35.1 to 112.0 x 10(9)/L; Sysmex R-1000: 0.6-1.85%, 28.0 to
      85.0 x 10(9)/L). The overall imprecision was lower for the instruments than for
      the microscopic method (Miles H.3: coefficient of variation, 11.6%; R-1000:
      coefficient of variation, 4.2%; microscopic method: coefficient of variation,
      24.2%). The Miles H.3 shows a good correlation with the other methods, yet it
      overestimated the low values with respect to both the microscopic method
      (intercept, 0.55; slope, 0.70) and the R-1000 (intercept, 0.44; slope, 0.78).
      This became particularly pronounced in patients with marrow aplasia. CONCLUSIONS:
      Miles H.3 can produce results with an acceptable degree of accuracy. The
      agreement with the dedicated fluorescence-based flow cytometer R-1000 at normal
      and high concentrations is also good. The possibility of providing reticulocyte
      indices as well as erythrocyte indices (mean volume, mean hemoglobin content,
      mean hemoglobin concentration) and the relative dispersion indices could be
      useful in understanding red cell pathophysiology in normal and iron deficient
      patients.

PMID- 7503664
TI  - Helicobacter heilmannii-like spiral bacteria in gastric mucosal biopsies.
      Prevalence and clinical significance.
AB  - BACKGROUND: Gastric Helicobacter pylori (Hp) is highly associated with
      histological gastritis and peptic ulcer disease, yet Helicobacter heilmannii (Hh,
      also known as Gastrospirillum hominis) may be a less frequent gastric pathogen
      about which less is known. PATIENTS AND METHODS: We evaluated 1223 gastric
      biopsies from 1042 upper endoscopies with biopsies performed over 1 year. Spiral
      bacteria were specifically sought in biopsies from 912 endoscopies. Clinical and
      pathologic data from patients with unusual spiral bacteria were tabulated and
      sera were evaluated for anti-Hp antibodies. RESULTS: The histologic prevalences
      of Hp and Hh-like bacteria were 59% and 0.5%, respectively, in 912 endoscopies.
      All four patients with Hh-like spiral bacteria had gastrointestinal symptoms and
      histologic gastritis. Two had immigrated from the Philippines and one from
      Belgium. Endoscopic findings and clinical course varied. One improved
      spontaneously; one improved following antibiotic therapy. One patient's symptoms
      and bacteria persisted without therapy. One patient coinfected with Hp was
      treated with apparent clearance of Hh but persistence of Hp. CONCLUSIONS:
      Helicobacter heilmannii-like bacteria can be distinguished from Hp with routine
      histologic stains; both bacteria are irregularly distributed. Helicobacter
      heilmannii appears to be a significant though uncommon cause of gastric
      inflammation. Some patients with Hh-like bacteria may benefit from anti-Hp
      therapy.

PMID- 7503665
TI  - Intimate association of eosinophils to collagen bundles in eosinophilic
      myocarditis and ranitidine-induced hypersensitivity myocarditis.
AB  - BACKGROUND: Eosinophilic myocarditis is an inflammatory condition of the heart in
      which the infiltrate is composed predominately of eosinophils. DESIGN: We
      identified three cases of eosinophilic myocarditis in which the infiltrating
      eosinophils showed a remarkable intimate association with bundles of collagen.
      Two of the hearts examined were explants from heart transplant recipients with
      hypersensitivity myocarditis at the time of transplant and the third was from an
      autopsied patient with Churg-Strauss syndrome. These hearts were examined using
      light and electron microscopy. The cellular infiltrate in all three cases was
      characterized using immunoperoxidase stains with a panel including antibodies
      against myeloperoxidase, common leukocyte antigen (CD45), B lymphocytes (CD20), T
      lymphocytes (CD3), active-memory T lymphocytes (CD45RO), inactive T lymphocytes
      (CD45RA), and macrophages (CD68). RESULTS: Ultrastructural examination in all
      three cases confirmed the apposition of eosinophils to both large bundles of
      collagen and smaller aggregates of collagen fibrils. The eosinophils and the
      bundles of collagen stained strongly for myeloperoxidase, suggesting at least
      partial degranulation of the eosinophils. A KP-1 stain (CD68) revealed
      macrophages admixed with the eosinophils adjacent to the collagen bundles, and
      stains for CD45RA (naive lymphocytes) and CD45RO (memory T cells) showed an
      interstitial infiltrate of predominantly CD45RO-positive cells. Clinically, the
      cardiac decompensation of one of the transplant patients was most likely due to
      ranitidine-induced hypersensitivity myocarditis. CONCLUSIONS: These results
      suggest that some cases of eosinophilic myocarditis may be caused by the
      expression of novel antigens bound to collagen bundles. In one of the patients
      awaiting cardiac transplant, cardiac decompensation was temporally associated
      with ranitidine therapy, an agent not previously implicated as a cause of
      hypersensitivity myocarditis.

PMID- 7503666
TI  - An intraperitoneal tumorous mass caused by granulomas of microfibrillar collagen
      hemostat (Avitene).
AB  - Microfibrillar collagen hemostat (Avitene) is an absorbable topical hemostatic
      agent prepared from purified bovine corium collagen. Herein, we report the case
      of a 56-year-old woman who had undergone an ovariohysterectomy for an ovarian
      mucinous cystadenocarcinoma 3 months previously and then required a second
      operation for an intraperitoneal mass associated with microfibrillar collagen
      hemostat. Microscopically, the resected mass was composed mostly of foreign-body
      granulomas with microfibrillar collagen hemostat materials. Microfibrillar
      collagen hemostat was used to control bleeding during the first operation. In a
      very small portion, however, a recurrent mucinous cystadenocarcinoma was also
      present. This case is worthy of note in that microfibrillar collagen hemostat may
      produce huge granulomatous masses that clinically mimic a neoplasm, inducing
      unnecessary and extensive treatment.

PMID- 7503667
TI  - Primary adrenal leiomyosarcoma in a man with acquired immunodeficiency syndrome
      (AIDS). Further evidence for an increase in smooth muscle tumors related to
      Epstein-Barr infection in AIDS.
AB  - We report a rare primary adrenal leiomyosarcoma in a 30-year-old, human
      immunodeficiency virus--positive man. This is, we believe, the third documented
      case in the English literature of this tumor in this site, and the first to be
      reported in an adult male with acquired immunodeficiency syndrome. The smooth
      muscle origin of this tumor was apparent by routine microscopy and confirmed by
      positive immunostaining for smooth muscle actin. The patient is presently well
      and shows no evidence of recurrence 20 months after surgery. The present findings
      are discussed with reference to the reported rising incidence of smooth muscle
      tumors in human immunodeficiency virus--infected patients and the associated
      etiologic role of Epstein-Barr virus in the pathogenesis of these tumors.

PMID- 7503668
TI  - Basaloid-squamous cell carcinoma of the bronchus. Report of a case with review of
      the literature.
AB  - Basaloid-squamous cell carcinoma (BSCC) is a variant of squamous cell carcinoma
      with biphasic basaloid and squamous features. Recognition of BSCC is important
      because this lesion can be confused with less aggressive lesions, such as adenoid
      cystic carcinoma. BSCC is typically detected at an advanced stage in smokers,
      alcoholics, and older individuals; adenoid cystic carcinoma is not associated
      with smoking or alcohol, and it typically occurs in younger individuals.
      Approximately 88 cases of BSCC in the upper aerodigestive tract have been
      recorded since its first description in 1986. We report one case of endobronchial
      BSCC. Cytologically, both squamous and basaloid features were identified,
      including elongated, irregular, globular, extracellular, hyaline material.
      Immunohistochemical studies showed two distinct populations of cells: the
      squamous component, positive for cytokeratin (AE1 + AE3) and negative for smooth
      muscle actin, epithelial membrane antigen, S100 protein, and type IV collagen;
      and the basaloid component, positive for all of the above markers, with minimal
      staining for cytokeratin (AE1 + AE3). The electron microscopy demonstrated
      desmosomes in the squamous component and replication of the basal lamina in the
      basaloid component. We conclude that BSCC of the bronchus is similar to BSCC in
      the upper aerodigestive tract and should be regarded as a distinct entity.

PMID- 7503669
TI  - Postirradiation colitis cystica profunda. Case report and literature review.
AB  - We report a rare case of rectosigmoid stricture associated with colitis cystica
      profunda that occurred 21 years after local therapeutic irradiation given for
      carcinoma of the bladder. We reviewed the literature and compared the clinical
      features, etiology, and macroscopic findings. The pathogenesis of the lesion may
      be related to repeated ulceration and regeneration, while chronic colonic
      ischemia may also play a role. The recognition of this rare entity is important
      because of its low-power "penetrating" architecture, which may be mistaken
      histologically as well-differentiated adenocarcinoma.

PMID- 7503670
TI  - Adenomyomatous hyperplasia of the gallbladder with perineural invasion.
AB  - We report three examples of either localized or segmental adenomyomatous
      hyperplasia of the gallbladder in association with cholelithiasis. Two patients
      were women, 58 and 81 years of age, and the third was a 62-year-old man. The
      finding of perineural invasion by epithelial ductal structures in two cases and
      of perineural and intraneural invasion in the third case led to initial diagnoses
      of well-differentiated adenocarcinoma. The presence of mucinous metaplasia in
      some of the cystically dilated ductal structures and the diffuse proliferation of
      pyloric-type glands probably contributed to the erroneous diagnosis of
      adenocarcinoma. Although the mechanism by which the epithelial structures invade
      perineural spaces is unknown, we offer two possible explanations: (1) extension
      and growth of epithelial ductal structures along tissue planes of least
      resistance, such as the perineural space, and (2) growth of hyperplastic nerve
      trunks in close proximity to or within epithelial structures. The pattern of
      perineural invasion in cases of adenomyomatous hyperplasia should not be confused
      with adenocarcinoma. Attention to the general architecture of the lesion and the
      bland cytologic features of the glands and ductal structures should prevent this
      misinterpretation. The gallbladder should be added to the list of organs in which
      perineural invasion by benign epithelial structures has been described.

PMID- 7503672
TI  - The serology of hepatitis C virus (HCV) infection: antibody crossreaction in the
      hypervariable region 1.
AB  - We determined the NS1/E2 N-terminal sequence including the hypervariable region 1
      (HVR1) from five individuals chronically infected with HCV: two from the Czech
      Republic and three from Germany. From each sequence, six 12-mer overlapping
      peptides were synthesized and used in a peptide scan to evaluate seroreactivity
      of each of those patients, as well as three anti-HCV positive blood donors to the
      different isolates. We could show the general presence of antibodies to multiple
      HVR1 specific sequences reflecting the existence of multiple variants in infected
      persons. Finally, we observed the persistance of HCV infections in all
      individuals despite an active humoral response directed against the virus.

PMID- 7503671
TI  - Group A rotavirus G type prevalence in two regions of Hungary.
AB  - Rotaviruses are a major cause of gastroenteritis in children world-wide.
      Rotaviruses are antigenically complex, with multiple serotypes (G types). The
      first longitudinal study of group A rotavirus serotype (G type) distribution in
      Hungary is reported. Neutralizing monoclonal antibodies specific for G1, G2, G3,
      and G4 were used in an enzyme immunoassay to determine the antigenic variation of
      group A rotaviruses in two collections of stool specimens assembled from 1984
      1992 in Baranya County, southwest Hungary, and from 1988-1992 at the Central
      Hospital for Infectious Diseases in Budapest. Ninety-two percent of the 1215
      virus-positive samples were typed as follows: G1 (81%), G2 (4%), G3 (1%), G4
      (5%), or mixed type (1%). G1 was the predominant type during the entire study
      period with the exception of the 1988/1989 rotavirus season in Baranya County
      when G4 predominated. Among G1 strains, different electropherotypes were detected
      with a shift of the predominant G1 electropherotype(s) each 2 to 3 years. G
      typing from two longitudinal collections established regional differences within
      Hungary in the prevalence of rotavirus antigenic types among children with
      rotavirus-associated diarrhea. These are the first longitudinal rotavirus typing
      results for Hungary and Central Europe.

PMID- 7503673
TI  - Inhibition of the intracellular transport of influenza viral RNA by actinomycin
      D.
AB  - In primary chicken embryo cells infected with fowl plague virus addition of
      actinomycin D at defined times during the infection cycle has different
      consequences on viral replication. If actinomycin D is added immediately after
      infection with a concentration, which inhibits viral RNA synthesis only
      partially, it interferes with the nucleo-cytoplasmic transport of all viral RNA
      species (mRNA and vRNA) so far tested. If actinomycin D is present during
      infection (adsorption, penetration and uncoating) no viral RNA is synthesized,
      and the nucleocapsid of the infecting virus does not reach the nucleus, as shown
      by fluorescent antibodies. Therefore the primary effect of actinomycin D on
      influenza virus replication is on the transport of the incoming vRNPs from the
      cytoplasm to the cell nucleus, which is the cell compartment where transcription
      takes place.

PMID- 7503674
TI  - Prolonged infection of mouse brain neurons with murine cytomegalovirus after pre-
      and perinatal infection.
AB  - The susceptibility of mice at different developmental stages to a relatively low
      titer of cell culture-passaged murine cytomegalovirus (MCMV) infection was
      compared in terms of the urinary excretion of MCMV examined by plaque assay and
      in terms of the distribution of viral infection, determined by
      immunohistochemistry, using antibodies specific to the early nuclear antigen of
      MCMV. Viral infection on day 8.5 of gestation (E8.5) into the conceptus and
      intraperitoneal infection on day 15.5 of gestation (E15.5), postnatal day 2 (P2),
      postnatal day 11 (P11), and 30 days after birth (P30), respectively, were
      performed. Embryonal and perinatal mice were more susceptible to MCMV in terms of
      urinary excretion of the virus and the presence of viral antigen-positive cells
      in the brain, lungs, and kidneys. In the embryonal and perinatal infection, the
      viral antigen-positive cells in the neurons of the cerebral cortex and
      hippocampus were retained late after birth, even though the positive cells in the
      lungs and kidneys had disappeared. In the mice infected on E8.5, small clusters
      of viral antigen-positive cells were detected only in the cortex and hippocampus
      late after birth, without the urinary excretion of virus. These results suggest
      that when mice are infected with MCMV at the embryonal and perinatal stages,
      elimination of the infected neurons is delayed compared with that of the other
      cells in the lungs and kidneys. These findings provide a model for the analysis
      of pathogenesis of the subclinical congenital CMV infection that manifested
      clinically late after birth in humans as brain disorders.

PMID- 7503675
TI  - Mapping of a functional region conferring nuclear localization of pseudorabies
      virus immediate-early protein.
AB  - The immediate-early protein (IE180) of pseudorabies virus (PrV) is localized
      predominantly in the nuclei of infected cells. To define the nuclear localization
      signals within IE180, we prepared truncated mutants of IE180 and analyzed their
      localization in the transfected cells by indirect immunofluorescence. Analysis of
      mutants truncated from the carboxy-terminal end of the 1460-amino acid
      polypeptide showed that two regions including a short sequence of basic amino
      acid residues were associated with the nuclear localization of IE180. To assess
      whether these regions substantially function as signals for nuclear localization
      of the IE180 molecule, we then constructed two deletion mutants lacking each
      region. A mutant lacking amino acids 333 to 575 was detected in the nuclei of the
      transfected cells, whereas the other mutant lacking amino acids 900 to 950 was
      detected mainly in the cytoplasm. These results suggest that the region of amino
      acids 900 to 950 is responsible for nuclear localization of IE180.

PMID- 7503676
TI  - Evaluation of complete genome sequences and sequences of individual gene products
      for the classification of hepatitis C viruses.
AB  - Comparisons of genome and polyprotein sequences of hepatitis C virus (HCV)
      isolates world-wide has led to the identification of nine major genotypes and
      many subtypes. This classification is based on either complete genome/polyprotein
      sequences or sequence data from the 5' noncoding region, core, E1, NS3 or NS5B
      genes. The relative merit of different gene segments as taxonomic markers and the
      validity of the resulting assignments is not clear at this stage. To resolve the
      taxonomy of HCV genotypes and subtypes, we have compared the complete genome and
      polyprotein sequences of 19 HCV isolates available in the databases as well as
      sequences of individual genes and gene products of these isolates. Based on the
      correlation between sequence relationships and taxonomic assignments of other RNA
      viruses, we show that the nine major genotypes of HCV represent nine distinct
      virus species and their subtypes subspecies. Our sequence comparison of the 5'
      noncoding regions and the individual gene products suggests that E2, NS2, NS5B,
      E1, NS4A, NS4B and NS5A (in that order) are the most appropriate regions for the
      discrimination between species, subspecies and strains of HCV. The 5' noncoding,
      core and NS3 regions are less effective in distinguishing between species,
      subspecies and strains. Based on a comparison of the polymerase sequence
      identities of HCVs, pestiviruses and flaviviruses as well as the recent
      information on the size and morphology of HCV virions, we propose that HCVs,
      pestiviruses and flaviviruses should be classified into three separate families,
      named Hepciviridae, Pestiviridae and Flaviviridae, respectively rather than three
      genera of the Flaviviridae as currently classified. We also propose "Hepcivirus"
      as the genus name for HCVs.

PMID- 7503677
TI  - Antigenic relationships of hantavirus strains analysed by monoclonal antibodies.
AB  - The antigenic relationships among 71 hantavirus strains, isolated from rodent
      species or humans in several geographic regions, were examined by
      immunofluorescence assay (IFA) using human patient sera and a panel of 22
      monoclonal antibodies prepared against Hantaan, Seoul, and Puumala viruses. The
      study included virus strains, mainly from the former USSR, for which little or no
      serological data were available. Fifty-nine of the 71 isolates could be placed
      into five antigenic groups of hantaviruses, Hantaan (HTN), Puumala (PUU), Seoul
      (SEO), Prospect Hill (PH), Dobrava/Belgrade (DOB). Twelve isolates were found
      antigenically closely related to, but distinct from, HTN (2 strains), PUU (4
      strains) and PH (6 strains), respectively. The antigenic characteristics of these
      12 isolates suggested two supplementary antigenic subgroups of HTN, one of PUU,
      and two of PH. The two antigenic subgroups of HTN included strains isolated in
      the Far-East of Russia. The PUU subgroup included strains isolated in European
      Russia as well as strains isolated in Far-Eastern Russia. The PH group comprised
      two subgroups, both represented by strains isolated from M. fortis in Far-Eastern
      Russia. The results showed that the PUU and PH antigenic groups are more complex
      than previously known and that PH-like virus strains isolated in Russia are
      antigenically more closely related to PUU virus when compared to prototype PH
      virus isolated in the USA.

PMID- 7503678
TI  - Human immunodeficiency virus nucleocapsid protein stimulates strand transfer from
      internal regions of heteropolymeric RNA templates.
AB  - We have examined the influence of HIV nucleocapsid protein (NCp) on strand
      transfer from internal regions of a heteropolymeric RNA template. The system
      consisted of a DNA-primed 225 nucleotide RNA donor template, on which reverse
      transcriptase initiated primer extension, and a 189 nucleotide RNA acceptor
      template, to which extended primers could transfer. The last 133 nucleotides on
      the 3' end of the acceptor were homologous to an internal region on the donor,
      limiting homologous strand transfer to this region. Primers extended to the end
      of the donor were 212 nucleotides while those transferred to, and extended on the
      acceptor were 259 nucleotides in length. The rate of strand transfer and the
      level of transfer products increased several-fold when nucleocapsid was included
      in the reactions. The increase was due, at least in part, to the transfer to, and
      extension on the acceptor, of incompletely elongated primer-extension products
      that were "chased" into transfer products in the presence of nucleocapsid.
      Nucleocapsid did not directly influence reverse transcriptase elongation as the
      enzyme processivity (number of nucleotides incorporated before the enzyme
      dissociates from the primer-template) was approximately the same in the presence
      and absence of nucleocapsid.

PMID- 7503679
TI  - Molecular epidemiology of foot-and-mouth disease (FMD) in Israel in 1994 and in
      other Middle-Eastern countries in the years 1992-1994.
AB  - The reverse transcriptase-polymerase chain reaction (RT-PCR) and direct
      sequencing were employed in the diagnosis and typing of foot-and-mouth disease
      virus (FMDV) in samples taken during the 1994 disease outbreak in Israel. Using
      PCR, virus isolation and serological methods it was shown that the 1994 disease
      outbreak in Israel and other Middle-Eastern countries was caused by O1 type
      virus. Direct PCR sequencing of VP1 genes and homology analysis of the virus
      isolates revealed that there were two distinct outbreaks in Israel. The first
      originated in Jordan, moved to the West Bank territory and then to the Lower
      Galilee. The second outbreak, caused by another virus, was responsible for
      disease outbreaks in South Lebanon, Upper Galilee and the Golan Heights. When
      viral sequences of isolates from the 1993 outbreaks in Egypt and Lebanon were
      included in the analysis, they showed a high degree of VP1 sequence homology
      between themselves, suggesting a common origin.

PMID- 7503680
TI  - Occurrence and role of an early antigen and evidence for transforming ability of
      porcine circovirus.
AB  - By means of indirect immunofluorescence assay (IFA) using natural swine immune
      serum and hyperimmune serum from rabbits infected with porcine circovirus (PCV),
      a PCV antigen was detected present prior to the onset of viral and cellular DNA
      synthesis in nucleoli of cells of synchronized and growth stimulated infected PS
      cell cultures grown for more than 12 h in the presence of hydroxyurea. The number
      of cells containing specifically fluorescing nucleoli increased with increasing
      time of growth in the presence of hydroxyurea. The concomitant increase in the
      number of cells containing virus structural (VS) antigen in the nuclei and the
      increase in the amount of replicative (RF) DNA and accompanying 5 S DNA after
      release from the hydroxyurea block suggest that EA is involved in induction of
      PCV DNA replication. Primary pig kidney cell cultures persistently infected with
      PCV survived mock-infected control cultures for 16 passages. They had lost
      contact inhibition and formed cell colonies in soft agar at a ratio of 0.1 to
      0.4%. Cell lines derived from agar colonies showed properties of transformed
      cells e.g. low requirement for serum growth factors, ability to overgrow a
      continuous cell layer, anchorage independence of growth. In transformed cells
      stimulated to growth and grown in the presence of hydroxyurea, non-structural
      viral antigen visible by IFA in nucleoli and VS antigen located in the cytoplasm
      were expressed. Contrary to virus bound nuclear VS antigen in productive
      infection, accumulation of cytoplasmatic VS antigen was independent of DNA
      synthesis and caused cell destruction, thus limiting growth of cell layers and
      colonies in soft agar.

PMID- 7503681
TI  - Expression, purification, and use as an antigen of recombinant sugarcane mosaic
      virus coat protein.
AB  - A high titre (1:10,000) antiserum was raised in a rabbit against the coat protein
      of sugarcane mosaic potyvirus (SCMV), by injecting a preparation of recombinant
      coat protein purified from a fusion protein expressed in E. coli. The fusion
      protein consisted of the MalE maltose binding protein (MBP) and the viral coat
      protein separated by the protease factor Xa cleavage site. The fusion protein was
      encoded by the plasmid pMAL-cCPM, which was constructed by cloning a modified
      coat protein gene to the 3' end of the MBP/factor Xa coding region. The coat
      protein gene was modified by site-directed mutagenesis so that the ATG start
      codon in the original construct was replaced by the codon AGC, deleting the NcoI
      restriction site (C/CATGG) and creating a unique Eco47III site (AGC/GCT).
      Endonuclease restriction with Eco47III resulted in a DNA fragment with GCT as the
      first three nucleotides. This triplet encodes alanine, which is the proposed N
      terminal amino acid residue of the mature native coat protein. This modified coat
      protein coding region was ligated directly behind the nucleotide code for the
      amino acid recognition sequence for factor Xa. Expression was induced with IPTG
      and the recombinant fusion protein was extracted from the bacterial lysate by
      amylose resin column affinity chromatography and the two domains separated by
      factor Xa proteolysis. The coat protein was then purified from the maltose
      binding protein by ion exchange chromatography in buffer containing 6 M urea. A
      highly purified sample which contained 150 micrograms of both full-length and
      truncated coat proteins, was recovered from a litre of bacterial broth. The
      antiserum reacted with native coat protein in SCMV-infected sugarcane, and with
      recombinant coat proteins expressed in E. coli and sugarcane protoplasts with
      little or no cross-reaction with sugarcane proteins.

PMID- 7503682
TI  - Attachment and entry of infectious pancreatic necrosis virus (IPNV) into CHSE-214
      cells.
AB  - Infectious pancreatic necrosis virus (IPNV) attaches to CHSE-214 cells through
      two types of cell components: specific and non-specific ones. Competition
      experiments with inactivated IPNV showed that IPNV requires specific components
      to productively infect cells. Just a low amount of adsorbed IPNV enters the cell.
      After 20 minutes, part of the adsorbed IPNV was internalized into acid
      compartments. Also, the viruses adsorbed on the cell surface require similar
      periods of time to escape from the neutralization of antibodies.

PMID- 7503683
TI  - Complete genomic RNA sequences of cucumber mosaic virus strain NT9 from Taiwan.
AB  - The nucleotide sequences of the RNAs 1, 2, and 3 of the cucumber mosaic virus
      (CMV) Taiwan isolate NT9 were determined and compared at both the nucleotide and
      amino acid levels with those of CMV strains Fny, Y, O from subgroup I and strain
      Q from subgroup II. NT9-CMV has an unique feature at the C-terminus of the 3a
      protein which contains four extra-amino acids. All three RNAs and their encoded
      proteins, except 2b, of NT9-CMV share more than 90% identity with those of
      strains in subgroup I, and 72%-85% identity with Q-CMV. The results indicated the
      conservation of sequences of CMV derived from different geographical locations.

PMID- 7503684
TI  - Host cell antigenic profile acquired by HIV-1 is a marker of its cellular origin.
AB  - HIV-1 acquires cell membrane proteins during budding. The cell membrane proteins
      (CMP) profile of laboratory HIV-1 strains grown in different host cells was
      established, by using an immobilized antibody capture (IAC), to verify whether
      CMPs present on HIV-1 correlate with its host cell origin. HIV-1 grown in
      different cell lines incorporates cell markers such as CD3, CD19, CD14, CD31 and
      IL 2-R, according to the distinctive expression of these antigens on the host
      cells. Furthermore, also T-tropic and monocytotropic HIV-1 strains display host
      cell specific markers, supporting the hypothesis that virus associated CMPs are a
      marker of host cell origin.

PMID- 7503685
TI  - Role of glycoprotein gD in the adhesion of pseudorabies virus infected cells and
      subsequent cell-associated virus spread.
AB  - Pseudorabies virus (PrV) infected cells in suspension are able to adhere to a
      monolayer of uninfected cells by means of PrV glycoproteins expressed at the
      outer cell membrane, with gB and gC playing a major role as ligands and a
      heparinlike substance as receptor. In order to investigate the role of gD in this
      process and subsequent transmission of infectivity to contact cells, experiments
      with a gD deletion mutant, heparin and a monoclonal antibody (Mab) against gD
      were performed. The first indication that gD is active during cell adhesion was
      found by the observation that the binding of gD- PrV infected cells was five
      times weaker than that of wild type (WT) PrV infected cells. Further evidence was
      given by the use of a Mab against gD. Preincubation of WT PrV infected cells with
      this Mab led to a reduction of the percentage adhering cells from 69% to 49%. The
      same Mab inhibited the heparin independent and heparin resistant binding of WT
      PrV infected cells indicating that gD is important during both processes.
      Furthermore, it was demonstrated in a plaque assay that, after contact with a
      monolayer, gD- PrV infected cells in suspension were able to induce plaques with
      an efficiency of 1%. In conclusion, we can state that beside the interaction of
      the ligands gB and gC with a heparinlike receptor also the interaction of gD with
      a receptor which differs from a heparinlike substance mediates the binding of WT
      PrV infected cells to uninfected cells and that gD is not essential for the
      subsequent cell-to-cell spread of the virus.

PMID- 7503686
TI  - Sequence variation in the L1 gene of human papillomavirus type 16 from Africa.
AB  - A 297 bp fragment of the HPV 16 L1 gene was sequenced from 35 isolates
      originating from normal cervical scrapes, cervical intraepithelial neoplasia
      biopsies and cervical carcinoma biopsies from South African women. A total of six
      point mutations that differed from the prototype HPV 16 sequence were detected in
      various combinations, giving rise to six distinct types of variants. Only one of
      the isolates had a sequence identical to the prototype. Our results indicate that
      the HPV L1 gene is conserved and there is no evidence that specific viral HPV L1
      variants are associated with specific pathology.

PMID- 7503687
TI  - Relationships of tailed phages: a survey of protein sequence identity.

PMID- 7503688
TI  - In memoriam R. E. F. Matthews (1921-1995)

PMID- 7503689
TI  - Genetic and antigenic variation in the haemagglutinin of recently circulating
      human influenza A (H3N2) viruses in the United Kingdom.
AB  - Variation in the haemagglutinin (HA) gene of influenza A (H3N2) viruses isolated
      in the U.K. and abroad from 1992-1994, was determined by nucleotide sequencing of
      the HA1 domain of the HA gene. Viruses isolated in the U.K. early in the 1992-93
      season were from the A/Beijing/353/89 lineage and were replaced later that season
      by viruses from the A/Beijing/32/92 lineage. Viruses from the new lineage
      continued to be isolated during the 1993-94 season, but were heterogeneous. Most
      of these isolates were more closely related to an A/Beijing/32/92 variant, A Hong
      Kong/23/92, but could be distinguished into three groups by serology (of which
      one group was circulating during the previous season) and four groups based on
      sequence variation in the HA gene. However, phylogenetic analysis of
      antigenically-distinct isolates showed that the HA gene is evolving along one
      lineage. Sequence analysis identified mainstream, subgroup and strain specific
      amino acid substitutions. There was a broad correlation between the observed
      amino acid changes and the antigenic sites of the HA. The results of this study
      highlight the value of regular molecular analysis of circulating viruses.

PMID- 7503690
TI  - Bovine respiratory syncytial virus replicates minimally in bovine alveolar
      macrophages.
AB  - The interaction between two different bovine respiratory syncytial virus (BRSV)
      strains and bovine alveolar macrophages (BAMs) was studied in vitro. Bovine
      respiratory syncytial virus replicated minimally in BAMs and most of the virus
      produced remained cell-associated. Approximately 1 out of 1,000 BAMs produced
      infectious virus, a number that further declined during the 7 days of culture. In
      contrast, BAMs exposed to bovine parainfluenza 3 virus (PI3V) produced high
      amounts of infectious virus. The number of BAMs that contained BRSV antigen
      depended on the antigen load of the inoculum and not on the infectivity of the
      virus. Antibody mediated enhancement of infection was not detected. It is
      concluded that bovine alveolar macrophages exhibit a high intrinsic resistance to
      BRSV, but not to PI3V.

PMID- 7503691
TI  - BK virus and a new type of JC virus excreted by HIV-1 positive patients in rural
      Tanzania.
AB  - HIV-1 positive patients from Tanzanian villages near Shirati were examined for
      urinary excretion of the human polyomaviruses JC and BK using the polymerase
      chain reaction (PCR). BK virus (BKV) was detected in 11 of 23 individuals tested.
      The BKV DNA sequences were all closely related to prototype Gardner strain and
      BKV (DUN). In contrast, a new type of JCV, termed Type 3 [or JCV (Shi)], was
      identified in seven of these same 23 individuals by comparison with Type 1 and
      Type 2 sequences of the VP1/intergenic/T antigen region of U.S., European and
      Asian strains. This suggests that JCV and BKV, although closely related, have
      different evolutionary histories within the African population. The six BKV
      regulatory regions amplified all showed the archetypal configuration. However,
      two of the seven JCV regulatory regions showed rearrangements: a small deletion
      and an inverted repeat. JCV causes a fatal demyelinating disease, progressive
      multifocal leukoencephalopathy (PML), in about 5% of AIDS patients in Europe and
      the U.S.A., but only one case has been reported in Africa. Our results suggest
      that this rarity of PML is not due to the absence of JCV in the African
      population.

PMID- 7503693
TI  - Molecular analysis of rice ragged stunt oryzavirus segment 9 and sequence
      conservation among isolates from Thailand and India.
AB  - Nucleotide sequences of rice ragged stunt virus (RRSV) genome segment 9 (S9) from
      a Thai and an Indian isolate were determined. Both sequences are 1132 bp long,
      contain a single large open reading frame (ORF) spanning nucleotide residues 14
      to 1027 and are capable of encoding a protein of 38.5K. The two isolates are
      94.6% and 99.4% identical at the nucleotide and amino acid level, respectively.
      The authenticity of these coding sequences was confirmed by identifying a
      approximately 38K protein in the RRSV particle with an N-terminal amino acid
      sequence identical to that inferred from the S9 ORF. Furthermore, cDNA of S9 from
      each isolate incorporated into the bacterial expression vector pGEX3-X produced a
      fusion protein that reacted with antibodies raised against purified RRSV
      particles. Cleaving these fusion proteins with protease factor X liberated a
      approximately 38K polypeptide.

PMID- 7503692
TI  - Expression and characterization of the multiplied, recombinant preS1 antigen of
      hepatitis B virus.
AB  - The amino acid sequence encoded by the preS1 region of hepatitis B virus genome
      is expressed on the surface of virions and subviral particles. The preS1 region
      is involved in the recognition of specific receptors responsible for the
      attachment of HBV to the host cell. The cell receptor binding site was assigned
      to the preS1 (20-47 aa) fragment. In order to obtain a large quantity of preS1
      binding domains of HBV the expression vector pWX4 was constructed. It contains
      four tandemly joined DNA sequences, each coding for preS1 (20-49 aa), fused with
      the 3' end of a DNA fragment coding for 450 aa of beta-galactosidase. E. coli
      cells transformed with this vector produce fusion protein beta-gal-preSlx4 in the
      form of inclusion bodies. Owing to the specific trypsin digestion, the preSlx4
      domain was cleaved from the fusion protein. The resulting product, a 16 kDa
      protein, was isolated and purified by anion exchange chromatography. The presence
      of four Asp-Pro bonds in this sequence and the primary structure of the first 28
      N-terminal amino acids were determined. Following the confirmation of the
      antigenic properties, the recombinant preS1 protein was used for detection of the
      anti-preS1 response in sera from HBV infected patients.

PMID- 7503694
TI  - Correlation of virus replication, cytokine (TNF-alpha and IL-1) producing cells,
      neuronal necrosis and inflammation after intranasal infection of mice with herpes
      simplex virus strains of different virulence.
AB  - The number of TNF-alpha and IL-1 beta producing cells was investigated during the
      acute replication phase of herpes simplex virus (HSV) in trigeminal ganglia after
      intranasal infection with strains of different virulence. The highly virulent
      strain WAL replicated strongly and induced many cytokine producing cells early in
      the ganglia. The low virulent strain HFEM replicated less, only few cytokine
      producing cells were detected late. The thymidine-kinase negative (TK-) virus
      1301 did not replicate but produced some lymphocytic inflammation. The higher the
      virulence of strains of HSV-1 or -2 was, the stronger was the extent of
      histopathological lesions; moreover, a dissociation in time between replication
      and cellular reaction (granulocytic and lymphocytic) could be observed after
      infection with strains HFEM and TK- virus 1301. CD4 and CD8 positive cells could
      be detected mainly at the rim of necrotic areas, TNF-alpha and IL-1 beta
      producing cells, however, were scattered throughout the ganglia.

PMID- 7503695
TI  - Immunogenicity, antigenicity, and protection efficacy of baculovirus expressed
      VP4 trypsin cleavage products, VP5(1)* and VP8* from rhesus rotavirus.
AB  - Rhesus rotavirus (RRV) VP4 trypsin cleavage product VP5(1)*, a truncated form of
      VP5*, was expressed in baculovirus and found by immunoprecipitation to be
      antigenically similar to VP5* on the virion. Immunization of mice with VP5(1)*
      elicited neutralizing antibody that was found to be cross-reactive with viruses
      representing P genotypes 1, 3, 4, 6, 7, and 8. Baculovirus expressed trypsin
      cleavage products, VP8* (amino acids 1-246) and VP5(1)* (amino acids 247-474),
      were tested for their ability to elicit a protective response in a murine model
      of passive protection. These results were compared to those obtained with
      baculovirus expressed RRV VP4. Dams immunized with baculovirus expressed RRV VP4
      gave birth to pups protected from RRV virus challenge. Neither VP5(1)* nor VP8*
      was as effective at generating protective immunity as full length VP4. However,
      antibody to VP5(1)* was more effective than antibody to VP8* at mediating
      protection even though the neutralizing antibody titers as measured by
      hemagglutination inhibition and focus reduction neutralization were similar.

PMID- 7503696
TI  - Malignant lymphomas induced by an Epstein-Barr virus-related herpesvirus from
      Macaca arctoides--a rabbit model.
AB  - Animal models for Epstein-Barr virus (EBV) are restricted to some species of new
      world monkeys which develop malignant lymphoid tumours or benign
      lymphoproliferative diseases after virus inoculation. Similar pathological
      features were induced in rabbits by the EBV-related herpesvirus of Macaca
      arctoides (HVMA). In this study 17 of 32 rabbits infected with varying amounts of
      HVMA produced from MAL-1 cells developed lymphoproliferative disorders. In 13
      rabbits high-grade malignant lymphomas were detected, 4 rabbits revealed the
      histopathological feature of lymphoid hyperplasia. These lymphoproliferations
      were shown to be associated with HVMA by PCR and by the expression of EBV-like
      RNAs (EBER) in 14 and 10 cases, respectively. The homology in the polymerase gene
      region between DNA from EBV and HVMA, and from HVMA and the malignant tissue was
      found to be 94.8% and 100%, respectively. All the infected animals produced
      antibodies to antigens corresponding to early and late EBV proteins. By studying
      the HVMA expression in MAL-1 cells EBV-like proteins expressed in latency (EBNA1
      and EBNA2) and in the lytic cycle (VCA, EA) were detected. Our findings suggested
      that HVMA caused a symptomatic infection in rabbits with pathological features
      that fit the conditions of an animal model suitable for testing antiviral drugs
      and vaccines against EBV.

PMID- 7503697
TI  - Identification of cell membrane proteins linked to susceptibility to bovine viral
      diarrhoea virus infection.
AB  - Three monoclonal antibodies directed against cell surface molecules of bovine
      cells inhibited subsequent infections with bovine viral diarrhoea virus (BVDV).
      They specifically blocked the infectivity of three non-cytopathogenic and three
      cytopathogenic BVDV strains. These results showed that an important mechanism for
      virus uptake was inhibited. The ligand of the monoclonal antibody BVD/CA 17,
      which blocked infectivity most efficiently, was found on leukocytes from a wide
      range of domestic and wild even-toed ungulates using flow cytometric analysis. In
      contrast, the monoclonal antibodies BVD/CA 26 and BVD/CA 27 appeared to be
      specific for bovine cells. Immunoprecipitation of labelled bovine cell surface
      proteins showed that the three monoclonal antibodies bound to proteins with
      identical relative molecular masses (M(r)). Proteins of an apparent M(r) of 93 K
      and 60 K were precipitated from lysates of fetal bovine kidney cells
      irrespectively of the MAbs used.

PMID- 7503698
TI  - Coding strategy of the S and M genomic segments of a hantavirus representing a
      new subtype of the Puumala serotype.
AB  - The hantavirus strain Vranica was previously reported to have been isolated from
      a bank vole in Bosnia-Hercegovina and associated with the occurrence of
      hemorrhagic fever with renal syndrome (HRFS) in humans. The complete cDNA
      nucleotide sequences of the small (S) and medium (M) genomic RNA segments of this
      virus were determined. Major open reading frames were found in the S and M
      segment between nucleotide positions 43 and 1341 coding for a polypeptide of 433
      amino acid residues and between nucleotide positions 41 and 3,484 coding for
      1,148 amino acid residues, respectively. The analysis and the alignment of the
      nucleotide and the derived amino acid sequences with known sequences of other
      hantavirus strains demonstrate that Vranica resembles Swedish strains and
      represents a new virus subtype of the Puumala serotype distinct from the subtypes
      represented by virus strains CG18-20 and Sotkamo.

PMID- 7503699
TI  - Molecular cloning and complete nucleotide sequence of carnation Italian ringspot
      tombusvirus genomic and defective interfering RNAs.
AB  - The complete sequences of genomic and defective interfering (DI) RNAs of
      carnation Italian ringspot tombusvirus (CIRV) were determined. The genome (4760
      nt) has an organization identical to that reported for other tombusviruses except
      that the pre-readthrough domain of the viral replicase encoded by the 5'-proximal
      open reading frame (ORF) is larger. In particular, the N-terminal region of this
      protein differs from the corresponding region of the other members of the genus
      Tombusvirus and Carmovirus. Two DI RNAs were found in infected tissues whose
      sequences were completely derived from genomic RNA. The smaller molecule (474 nt)
      is contained completely within the larger molecule (656 nt), which suggests that
      it is derived from the larger one.

PMID- 7503700
TI  - A multiple alignment of the capsid protein sequences of nepoviruses and
      comoviruses suggests a common structure.
AB  - The amino acid sequences of the regions encoding the structural proteins of
      eleven nepoviruses and five comoviruses, two genera of the family Comoviridae,
      have been aligned. The properties predicted by computer analysis (three
      dimensional-3D-structure, hydrophobicity) are also correlated along this
      alignment, and aligned to the experimentally determined 3D structure of two
      comoviruses. It can thus be assumed that the 3D structure of the unique nepovirus
      coat protein matches that of the bipartite protomer found in the comovirus
      particles. In this model, the spatial locations of two amino-acid motifs
      characteristic of nepoviruses are in close vicinity, at the external surface of
      the virion. The coat proteins of nepoviruses and comoviruses may thus share a
      common evolutionary origin. A phylogenetic analysis was made using the multiple
      alignment, allowing a better understanding of the molecular relationships between
      these two groups of viruses.

PMID- 7503701
TI  - Detection of latent varicella zoster virus DNA and human gene sequences in human
      trigeminal ganglia by in situ amplification combined with in situ hybridization.
AB  - Varicella zoster virus (VZV) establishes latency in sensory ganglia following
      primary infection (chickenpox) and may reactivate decades later to produce zoster
      (shingles). The presence of VZV DNA in latently infected ganglia has been
      demonstrated by Southern blot hybridization as well as by polymerase chain
      reaction of DNA extracted from latently infected ganglia. Conflicting results
      have been obtained by in situ hybridization studies to determine the cell type in
      the ganglia harboring the latent VZV. To address this controversy we have
      utilized a more sensitive method than the previous studies. We have applied the
      technique of polymerase chain reaction to sections of ganglia from latently
      infected individuals and combined this with in situ hybridization to detect the
      amplified product. Primers specific for VZV were used to amplify VZV DNA in
      latently infected human trigeminal ganglia and demonstrated the presence of VZV
      DNA in neurons only. Sections from human kidney and ganglia from neonates as well
      as monkey ganglia served as controls and did not show amplification of VZV
      sequences. Amplification using primers for human genes, alpha tubulin and the
      oncogene Bcl-2, demonstrated the presence of these sequences in nearly all cells
      in the human tissues while only weak signals were seen in the monkey tissue. This
      is the first report where in situ amplification has been utilized to detect
      latent VZV in human ganglia.

PMID- 7503702
TI  - Expression and analysis of the NS2 protein of influenza A virus.
AB  - Influenza NS2 protein was expressed in Saccharomyces cerevisiae using a copper
      inducible promoter. The protein produced had a molecular weight of 13 kDa, was
      reactive with anti-NS2 antiserum and was localised to the yeast cell nucleus. Two
      hybrid analysis identified a direct protein-protein interaction between NS2 and
      the M2 protein of the virus, involving the C-terminal 163 residues of M1. A
      filter-binding assay localised the M1 binding region to the C-terminal 70 amino
      acids of NS2.

PMID- 7503703
TI  - Expression of the rubella virus structural proteins by an infectious Sindbis
      virus vector.
AB  - To assess the potential of an infectious Sindbis virus vector (dsSIN) as a
      eukaryotic expression vector, dsSIN recombinants which contain each of the
      rubella virus (RUB) structural proteins (C, E2, and E1) individually were
      constructed. Expression of the RUB proteins by each dsSIN recombinant was robust
      and processing was similar to that observed when these proteins were expressed
      using other vectors. The C and E2 recombinants, each of which contains a cassette
      of less than 1,000 nts, were stable through low multiplicity amplification;
      however, the E1 recombinant, which contains a 1700 nt cassette, was not.
      Therefore, use of the E1 recombinant is restricted to stock derived from the
      original transfection. The replication rate of dsSIN and the C and E2
      recombinants was similar, however, the replication rate of the E1 recombinant was
      slower. No phenotypic mixing of any of the RUB proteins in recombinant dsSIN
      virions could be detected.

PMID- 7503704
TI  - Sequence analysis of echoviruses in a major antigenic region eliciting
      enteroviral cross-reactive antibodies.
AB  - The amino acid sequence of an antigenic region known to elicit cross-reactive
      enteroviral IgG antibodies in VP1 is known for poliovirus and cox-sackievirus A
      and B. However, no corresponding data has been available for prevalent echovirus
      serotypes with great clinical impact. Such information was obtained by
      amplification of this region of the echovirus genome by PCR using biotinylated
      primers. The amplicon was subjected to solid phase sequencing using the dideoxy
      chain-termination method. Translated amino acid sequences for residues 26-55 of
      VP1 of the echoviruses revealed that the known cross-reactive region is highly
      conserved also in the echovirus serotypes.

PMID- 7503705
TI  - Sequence analyses and a unifying system of virus taxonomy: consensus via consent.

PMID- 7503706
TI  - International Committee on Taxonomy of Viruses (ICTV) activity report.

PMID- 7503707
TI  - [Septic arthritis of the pastern in cattle--clinical, radiological and
      sonographic findings and treatment].
AB  - Clinical, radiographic, sonographic, arthrocentesis and intraoperative findings
      in 19 cattle suffering from a septic arthritis of the proximal interphalangeal
      (p.i.p.) joint in 20 digits were evaluated retrospectively. In 6 cattle the
      p.i.p. joint was exclusively affected, in 13 animals a concurrent infection was
      ascertained in other 18 synovial cavities: digital flexor tendon sheath and the
      adjoining digital joints. As origin of the p.i.p. joint infection 11 cases showed
      perforating wounds, 6 cases a contiguous spread from adjacent purulent tissue
      affections and in 2 calves a haematogenous contamination was found. According to
      the progress of septic joint affection the increasing severity of the
      radiographic findings in this study were classified in 6 degrees. This systematic
      classification of the radiographic findings of septic arthritis in cattle is
      proposed as a basis for a comparable description and diagnosis of the
      radiographic signs. The sonographic imaging of the distended dorsal and plantar
      recesses of the p.i.p. joint in 3 cattle was proved to be a valuable adjunct to
      the other examination methods available. Five animals were slaughtered after
      diagnosis. An amputation through the distal third of the phalanx proximalis,
      respectively a modified disarticulation in the p.i.p. joint was performed in 14
      patients. After an average hospitalization of 4.6 weeks the 13 healed patients
      were dismissed.

PMID- 7503708
TI  - Leukocyte alkaline phosphatase and serum gamma-glutamil transferase activities in
      horses used for production of hyper immune sera.
AB  - The activities of leukocyte alkaline phosphatase (l-AP) and serum gamma-glutamil
      transferase (gamma-GT), and total leukocyte counts were determined in horses
      submitted to the production of hyper immune sera against tetanus (Clostridium
      tetani). The purpose of this work was to investigate the prospective changes of
      mentioned parameters in horses under the described circumstances. In addition,
      the suitability of these parameters in assessing the health condition of the same
      horses had to be evaluated. The average total leukocyte count increased in one
      month from the values considered as physiological (8.8 x 10(9)/L, Schalm et al.
      1975) to the value of 12 x 10(9)/L and remained at this level up to the end of
      the trial. The I-AP activities fell after 30 days of the trial for 100 units, and
      showed permanent slight decreasing tendency thereafter. On the contrary, the
      serum gamma-GT activity was increasing gradually throughout the whole trial. The
      results indicate the possibility of reflecting the dynamics of intensified
      leukocyte metabolism in the course of its function within the chronic
      inflammation, and development of accompanying pathological changes in the liver.
      In addition, the initialisation period of pathological changes in the organism of
      horses in experiment could be between the fourth and sixth month following
      exposure to antigen.

PMID- 7503709
TI  - [Occurrence and significance of different adhesion molecules--review].
AB  - The adhesion of leucocytes to endothelial cells is an important step in the
      migration of these cells into lymphatic tissue and to places of acute
      inflammation. These leucocytes do not only stick to altered endothelial cells
      during acute inflammation as part of the immun response. They also interact with
      normal endothelial cells in order to immigrate in lymphatic and extralymphatic
      tissue. Three cell surface molecule families regulate the tissue specific
      migration of leucocytes on the molecular level: integrin family, selectin family
      and the immunglobulin supergen family. This review reports the present state of
      research. It has to be taken in consideration, that almost every day new results
      will be found.

PMID- 7503710
TI  - [The stabilization of swine blood for hematologic studies].
AB  - Blood samples of 13 sows were preserved with ACD stabilizer with adenine, ACD
      stabilizer A (DAB) and heparin respectively and were stored in a refrigerator at
      4 degrees C over a period of 18 days. During this time the number of erythrocytes
      and leucocytes, the hematocrit and the hemoglobin concentration were determined
      10 times. The best preservation of erythrocytes was observed in ACD stabilizer
      with adenine. Compared to other stabilizers, preservation of leucocytes was best
      in ACD stabilizer A. The lysis of the white blood cells follows the exponential
      function y = ae-bt. ACD-stabilizers permit the preservation of erythrocytes and
      leukocytes for hematological examinations of swine blood over a period of up to
      five days.

PMID- 7503711
TI  - ["...that subsequently homeopathy will become nowhere as common as in veterinary
      medicine"--the history of veterinary homeopathy in Germany].
AB  - The subject of this article is the historical development of veterinary
      homoeopathy in Germany until 1945. Turning away from drastic healing methods
      around 1800, Samuel Hahnemann started to develop his homoeopathic system which
      since the 1820ies was also applied in the treatment of animals, especially by
      laymen. The number of homoeopathically-oriented veterinarians remained small.
      This is also true for veterinary-homoeopathic articles claiming to be scientific
      while there was a considerable number of popular articles to be found. The
      professors of the veterinary teaching institutions rejected homoeopathy. At the
      end of the 19th century hardly anything was heard about veterinary homoeopathy,
      at least among the professionals. Scientific success in human and veterinary
      medicine pushed Hahnemann's teachings and those of his successors into the
      background. In the 1920ies homoeopathy was revived and the position of the
      renowned surgeon August Bier played an important part in that. Members of the
      "Studiengemeinschaft fur tierarztliche Homoopathie" (Study Group for Veterinary
      Homoeopathy) which was founded in 1936 started to investigate the effects of
      homoeopathic drugs systematically. The war put an end to this project. The
      present situation of veterinary homoeopathy in Germany can be described as
      follows: Neither have allopathy and homoeopathy been united, as it had been
      predicted, nor has classical medicine accepted homoeopathy as a scientific
      discipline. Hahnemann's demand to make his teachings a part of the veterinary
      studies remains unfulfilled until today.

PMID- 7503712
TI  - Quantitation of APC mRNA in human tissues.
AB  - The aim of this study was to develop a method for quantitation of APC mRNA and to
      measure APC mRNA levels in human tissues. This was done using a competitive
      reverse transcription PCR with a synthetic RNA control. APC mRNA (pg/microgram
      total RNA) was quantitated in the following tissues: normal colon 133.6 +/- 69.0;
      normal duodenum 16.6 +/- 15.7; normal thyroid 30.4 +/- 20.3; normal esophagus
      65.2 +/- 58.8; colonic carcinoma 66.5 +/- 30.3; esophageal carcinoma 54.7 +/-
      26.5; papillary thyroid carcinoma 55.8 +/- 32.9 and colonic adenomas from
      patients with familial adenomatous polyposis 46 +/- 15. APC mRNA levels were
      significantly lower in the duodenum and thyroid than in the colon and esophagus.
      The quantity of APC mRNA was lower in colonic adenomas from FAP patients than in
      normal colonic mucosa (p < 0.05).

PMID- 7503713
TI  - Efficient regulation of gene expression by adenovirus vector-mediated delivery of
      the CRE recombinase.
AB  - We have constructed an E1-defective adenovirus (Ad) vector designated AdCAG-Cre
      containing the Cre recombinase gene derived from bacteriophage P1 under control
      of the cytomegalovirus immediate early enhancer-chicken beta-actin hybrid (CAG)
      promoter. We examined the Cre-loxP-based recombination by this Ad vector in C2C12
      cells bearing a reporter gene construct CAG-CAT-Z, which directs expression of
      the E. coli lacZ gene upon Cre-mediated excision of the CAT gene located between
      the CAG promoter and the lacZ gene. Nearly 100% of these cells were shown to
      start to produce beta-galactosidase after infection with the AdCAG-Cre vector at
      MOI 100. On the basis of this result, we discuss the possible use of the AdCAG
      Cre vector to manipulate the gene expression in mammalian cells.

PMID- 7503714
TI  - Galectin-3 binding potentials of mouse tumor EHS and human placental laminins.
AB  - Galectin-3, a lectin which binds to polyalctosamine chains of laminin, has been
      implicated as a modulator of cell to laminin interactions. In this study, we
      analyzed the relative binding of galectin-3 to mouse tumor and human placental
      laminins. Using gel overlay experiments, we have demonstrated that galectin-3
      preferentially binds to mouse tumor compared to human placental laminin. We have
      also demonstrated by Western blotting assays that mouse tumor laminin copurifies
      with endogenous mouse galectin-3. Lastly, we have demonstrated by periodate
      Schiff staining that mouse tumor has more sugar residues than human placental
      laminin. These analyses may explain why laminins purified from normal and tumor
      cells promote the attachment and spreading of certain cells differently.

PMID- 7503715
TI  - Characterization of a specific monoclonal antibody 9F5-3a and the development of
      assay system for oxidized HDL.
AB  - We obtained a monoclonal antibody 9F5-3a against oxidative low-density
      lipoprotein (LDL) modified with CuSO4 and established a sandwich ELISA for
      detection of oxidized high-density lipoprotein (oxHDL). The 9F5-3a was reacted
      strongly with oxHDL and to a lesser degree with oxLDL and LDL. In contrast,
      little or no reactivity was found with HDL. When the generation of oxHDL was
      limited by the addition of alpha-tocopherol and catalase, reactivity to 9F5-3a
      was reduced. Incubation of oxHDL with excess lyso-phosphatidylcholine (lyso-PC)
      also reduced immunoreactivity, but not by only lyso-PC. These results suggested
      that the epitope is possibly associated with oxHDL-linked lyso-PC induced mainly
      by the hydroxyl radical.

PMID- 7503716
TI  - Epidermal growth factor regulates expression of the mucous phenotype of rat
      tracheal epithelial cells.
AB  - The purpose of this study was to determine whether epidermal growth factor (EGF)
      regulates mucous differentiation of airway epithelial cells in culture. Reduction
      of the EGF concentration below 25 ng/ml, which is the concentration routinely
      used in rat tracheal epithelial cell cultures, resulted in a 2 to 3-fold decrease
      in the percentage of mucous cells as determined by a mucin monoclonal antibody.
      The amount of secreted mucin decreased more than 10-fold within 5 days after
      reducing the EGF concentration. MUC5 gene expression, which was previously shown
      to correlate with mucous differentiation, was also reduced more than 8-fold.
      Addition of 25 ng/ml EGF to EGF-deprived cultures resulted in rapid induction of
      MUC5 expression. Following tissue injury and during inflammation the release of
      EGF and its functional analogue TGF alpha have been observed and may be involved
      in the mucus hypersecretion characteristic of many airway diseases.

PMID- 7503717
TI  - Distinct phosphorylation sites differentially influence facilitated transport of
      an NLS-protein and its subsequent intranuclear binding.
AB  - We measured the nuclear transport of radiolabeled fusion proteins consisting of
      variants of the Simian Virus 40 large T antigen's nuclear localization sequence
      region linked to beta-galactosidase, itself a cytoplasmic protein. We
      microinjected the fusion protein variants into the cytoplasm of living Xenopus
      oocytes or supplied them to the surface of oil-isolated oocyte nuclei via paired
      beads or cytoplasm. Presence of the cdc2 kinase site (124T) on the amino flank of
      the nuclear localization sequence (126PKKKRKV132) greatly enhances facilitated
      transport through the nuclear pore complex; additional presence of the casein
      kinase II site (112S) enhances subsequent intranuclear binding.

PMID- 7503718
TI  - Characterization of chimeric heme-copper respiratory oxidases using subunits I of
      Escherichia coli cytochrome b o and Halobacterium salinarium cytochrome aa3.
AB  - We constructed chimeric enzymes with the Escherichia coli cytochrome bo and the
      Halobacterium salinarium cytochrome aa3 through recombinant DNA techniques and
      investigated their spectroscopic and biochemical properties. Although most of the
      chimeras could not retain hemes in the molecule, the chimeric enzyme containing
      helix VII of subunit I of the H. salinarium cytochrome aa3 showed the spectral
      properties similar to those of the native E. coli oxidase, suggesting that both
      the low-spin heme b and the high-spin heme o are associated with the chimeric
      subunit I. However, CuB was absent in the chimera. Helix VII of subunit I of the
      H. salinarium cytochrome aa3 is 70% similar to the counterpart of the E. coli
      cytochrome bo and further contains two invariant histidines which serve as the
      CuB ligands. These results indicate that helix VII must be arranged properly
      relative to helix VI which provides the third CuB ligand.

PMID- 7503719
TI  - Inhibition of bovine beta-trypsin by the active site titrant N alpha-(N,N
      dimethylcarbamoyl)-alpha-azaornithine p-nitrophenyl ester: a kinetic and X-ray
      crystallographic study.
AB  - Kinetics of the bovine beta-trypsin (trypsin) reaction with the active site
      titrant N alpha-(N,N-dimethylcarbamoyl)- alpha-aza-ornithine p-nitrophenyl ester
      (Dmc-azaOrn-ONp) was obtained at pH 6.2 and 21.0 degrees C. The results are
      consistent with the minimum three-step catalytic mechanism of serine proteinases
      involving a stable acyl.enzyme adduct. Dmc-azaOrn-ONp binds stoichiometrically to
      trypsin and allows the reliable determination of the active enzyme concentration
      between 1.0 x 10(-6) M and 3.0 x 10(-4) M. The three-dimensional structure of the
      trypsin.Dmc-azaOrn acyl.enzyme adduct has been solved by X-ray crystallography at
      1.8 A resolution (R = 0.153). The Dmc-azaOrn moiety of the active site titrant is
      accommodated in the serine proteinase active center, occupying the S1 specificity
      subsite, and is covalently linked to the OG atom of the Ser195 catalytic residue.

PMID- 7503720
TI  - Endothelin-1 induces rapid and long lasting internalization of the thrombin
      receptor in human glomerular epithelial cells.
AB  - Endothelin-1 acts as a potent autocrine and paracrine mediator in the kidney.
      Glomeruli and renal arterioles also express functional thrombin receptors which
      mediate the cellular effects of thrombin. Using the binding on glomerular
      epithelial cells of 125I-labeled ATAP2, a monoclonal antibody raised against the
      functional thrombin receptor, we demonstrate here that endothelin-1 induces
      thrombin receptor internalization in a dose- and a time-dependent manner. The
      maximal effect is observed at 10(-7) M endothelin-1 corresponding to
      internalization of approximately 25% of thrombin receptors. It is maximal at 20
      min and persists for at least 24 h. This effect is mediated by the endothelin
      receptor subtype A (ETA), and involves a pertussis toxin-sensitive G-protein and
      protein kinase C activation. Endothelin-1 does not induce thrombin receptor
      degradation nor change in thrombin receptor mRNA level after 2 h and 24 h of
      incubation. These results indicate that partial heterologous internalization of
      the functional thrombin receptor is induced by endothelin-1.

PMID- 7503721
TI  - Rho B-crystallin, an aldose reductase-like lens protein in the gecko
      Lepidodactylus lugubris.
AB  - The ocular lenses of the diurno-nocturnal gecko Lepidodactylus lugubris contain a
      monomeric 38-kDa protein at a level of 20 to 22% of the total water-soluble
      protein. Amino acid sequences of peptides from this protein are most similar--up
      to 72% identity--to mammalian aldose reductase, an NADPH-dependent reductase
      which normally occurs at house-keeping levels in the eye lens, and which is
      involved in the development of diabetic cataract. The sequences show 56% identity
      with rho-crystallin from lenses of the frog genus Rana. It is concluded that
      different genes from the same superfamily of NADPH-dependent reductases have been
      recruited to become highly expressed as lens proteins in at least two different
      evolutionary lineages. To reflect the relationship with frog rho-crystallin, the
      gecko lens protein is designated as rho B-crystallin. As for frog rho-crystallin,
      no enzymatic activity could be established for rho B-crystallin in the gecko
      lens. Up to now, rho B-crystallin has not been detected in lenses of other
      reptiles or amphibians.

PMID- 7503722
TI  - Stimulation of protein kinase C activity by compactin in vascular smooth muscle
      cells.
AB  - The effect of compactin (a lovastatin analogue) on vascular smooth muscle cells
      was studied at the level of cell proliferation and protein kinase C. It was
      observed: a) an inhibition of cell proliferation by compactin at a micromolar
      range, which was prevented by simultaneous addition of mevalonate; b) a
      stimulation of DNA synthesis with a shift in the cell cycle kinetics, either in
      the presence or absence of fetal calf serum and c) an increase in protein kinase
      C activity in compactin-treated cells in the G1 phase of the cycle. This increase
      was similar to the one elicited by calyculin A, an inhibitor of protein
      phosphatases of type PP-1 and PP-2A. It is suggested that compactin behaves as a
      PP-1/PP-2A protein phosphatase inhibitor, inhibiting proliferation of smooth
      muscle cells by a block of the cell cycle after the S-phase.

PMID- 7503723
TI  - Direct binding of F actin to the cytoplasmic domain of the alpha 2 integrin chain
      in vitro.
AB  - The transmembrane integrins have been shown to interact with the cytoskeleton via
      noncovalent binding between cytoplasmic domains (CDs) of integrin beta chains and
      various actin binding proteins within the focal adhesion complex. Direct or
      indirect integrin alpha chain CD binding to the actin cytoskeleton has not been
      reported. We show here that actin, as an abundant constituent of focal adhesion
      complex proteins isolated from fibroblasts, binds strongly and specifically to
      alpha 2 CD, but not to alpha 1 CD peptide. Similar specific binding to alpha 2 CD
      peptide was seen for highly purified F actin, free of putative actin-binding
      proteins. The bound complex of actin and peptide was visualized directly by
      coprecipitation, and actin binding was abrogated by removal of a five amino acid
      sequence from the alpha 2 CD peptide. Our findings may explain the earlier
      observation that, while integrins alpha 2 beta 1 and alpha 1 beta 1 both bind to
      collagen, only alpha 2 beta 1 can mediate contraction of extracellular collagen
      matrices.

PMID- 7503724
TI  - Constitutive expression of the thrombopoietin gene in a human hepatoma cell line.
AB  - The gene of thrombopoietin (TPO) has been cloned and identified to be identical
      to gene of the c-mpl ligand. It is known that the mRNA of TPO is expressed in
      liver and kidney. However, it is not clarified which cells in the liver produce
      TPO. Using a human hepatoma cell line, HepG2, we demonstrated that the TPO mRNA
      was expressed by liver parenchymal cells without any stimulation. To clarify the
      regulation of the expression of the TPO mRNA in HepG2 cells by cytokines, we
      assessed the effects of 5 cytokines, transforming growth factor-beta 1, activin
      A, platelet-derived growth factor, hepatocyte growth factor, and interleukin-6.
      These cytokines have no significant regulative effect on the expression of the
      TPO mRNA in HepG2 cells. Our results suggest that liver parenchymal cells may be
      the TPO producing cells and also suggest that some hepatoma cells may produce TPO
      constitutively.

PMID- 7503725
TI  - Functional expression of two forms of rat acyl-CoA oxidase and their substrate
      specificities.
AB  - Using the reverse transcription of RNA followed by the polymerase chain reaction,
      we cloned the cDNAs for the rat acyl-CoA oxidases I and II, which are produced by
      alternative splicing from a single gene, and developed a system for their
      expression in Escherichia coli. The homogeneous preparations of these enzymes,
      without proteolytic procession, showed oxidase activity with acyl-CoAs having
      various acyl-chain lengths. The two types of the enzyme exhibited different
      substrate specificities with respect to the acyl-chain length, acyl-CoA oxidase I
      showing the optimum activity at shorter chain-length relative to acyl-CoA oxidase
      II.

PMID- 7503726
TI  - PD 90780, a non peptide inhibitor of nerve growth factor's binding to the P75 NGF
      receptor.
AB  - Nerve growth factor is a peptide that supports the survival and differentiation
      of discrete neuronal populations in the peripheral and central nervous systems.
      NGF binds to both trkA, a tyrosine kinase receptor, and to the p75 nerve growth
      factor receptor, a protein lacking a consensus signalling sequence. We have
      identified a substituted pyrazoloquinazolinone, PD 90780, which inhibits binding
      of nerve growth factor to the p75 receptor. This inhibition of binding occurs due
      to PD 90780 binding to nerve growth factor, not to the p75 receptor. This
      compound may be useful in identifying the region(s) of nerve growth factor
      involved in binding to the p75 receptor and in clarifying the role of p75
      receptor in the actions of the neurotrophins.

PMID- 7503727
TI  - Downregulation of prohormone convertase-1 by a phorbol ester.
AB  - Acute TPA treatment (1h, 100nM) of a human pancreatic carcinoid cell line (BON)
      depletes cell contents of chromogranin A (CGA) and pancreastatin (PST), a peptide
      derived posttranslationally from CGA. Despite removal of TPA, BON cells continue
      to release CGA in an unregulated fashion whereas PST secretion is reduced
      substantially. TPA treatment also reduced prohormone convertase-1 (PC-1) protein
      and increased PC-1 mRNA levels. Together, these findings indicate that the TPA
      induced switch from a regulated to unregulated pattern of CGA secretion is
      accompanied by a decrease in the processing of CGA to PST and a decrease in the
      active form of a processing enzyme potentially involved in processing CGA to a
      smaller peptide, PST.

PMID- 7503728
TI  - The transformation of c-jun-overexpressing cells is correlated with IGFS-induced
      c-jun phosphorylation.
AB  - We have analyzed, in parental and c-jun-transfected rat liver epithelial (REL)
      cells, the capacity of the insulin-like growth factors (IGF1 and 2) to stimulate
      growth under anchorage dependent and independent conditions and the role of the c
      jun protein in the response to these factors. Although the increase of the
      proliferation of cells in monolayer was similar for the two lines, only the c-jun
      transfected cells formed colonies in soft agar after IGFs exposure. We showed
      that IGF1 and 2 did not modify the expression of c-fos or c-jun proteins during
      short-time exposures but both factors enhanced c-jun phosphorylation which
      suggests that this phenomenon could be involved in IGFs-regulated gene
      expression. Moreover, we showed that both the overexpression and the increase of
      phosphorylation status of c-jun protein were necessary to transform REL cells.

PMID- 7503729
TI  - Binding of adenylate kinase to RNA.
AB  - Adenylate kinase (ATP:AMP transphosphorylase) is a key enzyme in energy
      metabolism. The activity of its isoforms is subjected to multiple regulations. It
      is shown here that a specific fraction consisting of all adenylate kinase
      isoforms from tobacco leaves and tissue cultures does not bind to the anionic
      exchange-resin Mono Q. Sample pretreatment with ribonuclease could restore full
      binding to Mono Q, suggesting an association of adenylate kinase with RNA similar
      to the enzyme of Chenopodium rubrum (J. Chromatogr. 625: 13-19). We propose here
      that at least in vitro adenylate kinase can behave as an RNA-binding protein and
      that RNA-binding of adenylate kinase isoforms may be related to regulatory
      mechanisms.

PMID- 7503730
TI  - Nitric oxide contributes to tissue injury in mercuric chloride-induced
      autoimmunity.
AB  - Recent data has suggested a role for nitric oxide (NO) both in the induction of
      immunity and as an effector of tissue injury in experimental models of
      inflammation. In this study, we have tested the efficacy of two inhibitors of NO
      synthase, NG-monomethyl-L-arginine (L-NMMA) and aminoguanidine (AG), to modify
      the autoimmune leucocytoclastic necrotizing vasculitis which develops following
      the administration of mercuric chloride (HgCl2) to the Brown Norway rat. Neither
      agent affected the induction of autoimmunity as judged by plasma IgE titres or
      the degree of tissue neutrophil infiltration; however, L-NMMA did significantly
      attenuate tissue injury scores. We conclude that inhibition of NO synthase does
      not influence the induction of autoimmunity by HgCl2, but that NO does contribute
      to the development of tissue injury in this experimental model.

PMID- 7503731
TI  - Nucleotide sequences and the molecular evolution of the DMA and DMB genes of the
      bovine major histocompatibility complex.
AB  - cDNA clones encoding the bovine major histocompatibility complex (MHC) class II
      DM alpha- and beta-chains were isolated and characterized. The BoLA-DMA cDNA
      clone, MA7, encoded a primary translated product of 260 amino acids, which
      included a signal peptide of 26 amino acids and a mature polypeptide of 234 amino
      acids. The BoLA-DMB cDNA clone, MB6, encoded a primary translated product of 262
      amino acids, with a signal peptide of 18 amino acids and a mature polypeptide of
      244 amino acids. Comparison of the sequences and construction of a phylogenetic
      tree revealed that both clones are more closely related to human and mouse DM
      genes than to genes for conventional bovine class II alpha- and beta-chains.
      Thus, since the bovine DMA and DMB genes are so different from other class II
      sequences and show evidence of strong conservation (> 70%) among the bovine,
      mouse and human homologues, it seems likely that each of these cDNA clones
      encodes a functional product, which might perform an important function, as
      previously established in studies in mouse and man.

PMID- 7503732
TI  - Possible involvement of ubiquitination in neurofilament degradation.
AB  - Ubiquitinated proteins are components of intraneuronal inclusions found in
      several degenerative diseases. Immunohistochemical studies of neurofilament
      accumulations in Lewy bodies suggest their possible ubiquitination. We
      investigated in the present work the presence and the nature of ubiquitin
      epitopes in purified neurofilament preparations from spinal cord. Ubiquitin
      antibodies consistently label the medium molecular weight neurofilament subunit,
      and to a lower extent the two other subunits of the neurofilament triplet.
      Ubiquitinated neurofilament epitopes are removed in vitro by incubation of
      neurofilaments with a deubiquitinase purified from nervous tissues. Studies of
      neurofilament degradation in vitro revealed that addition of ATP and exogenous
      ubiquitin stimulates the proteolysis of neurofilament by crude soluble fractions
      from nervous tissues. These observations favor the hypothesis of a physiological
      function of ubiquitin-associated pathways in degradation of neurofilaments in
      situ.

PMID- 7503733
TI  - N23K, a gene transiently up-regulated during neural differentiation, encodes a
      precursor protein for a newly identified neuropeptide nociceptin.
AB  - We used a subtraction cloning approach to isolate a cDNA of N23K, whose mRNA and
      protein are transiently up-regulated in mouse NS20Y cells undergoing neurite
      outgrowth induced by treatment of dibutyryl cyclic AMP. N23K encodes a precursor
      protein for a newly discovered rat neuropeptide nociceptin. As with other
      neuropeptide precursors, the N23K protein contains a putative signal peptide rich
      in hydrophobic amino acids at the N-terminus. N23K mRNA is present only in brain
      and spinal cord in adult mouse, and is expressed at higher levels in early
      postnatal brain. These findings suggest that the N23K protein functions not only
      as a neuropeptide precursor but also as an important component in neuronal
      differentiation.

PMID- 7503734
TI  - Differential expression of five protein kinase C isoenzymes in FAO and HepG2
      hepatoma cell lines compared with normal rat hepatocytes.
AB  - We analyzed the expression of five protein kinase C (PKC) isoforms in cytosolic
      and membrane fractions from normal rat hepatocytes compared with those of two
      tumorigenic cell lines FAO and HepG2. Western blots with PKC-specific isoenzymes
      polyclonal antibodies provide evidences for the presence of the five isoforms
      alpha, beta II, delta, epsilon and zeta in normal rat hepatocytes. In hepatoma
      cells, we show differences in the level of expression, the molecular sizes and
      the responses to Phorbol 12-myristate 13-acetate (PMA).

PMID- 7503735
TI  - Differential distribution of heterogeneous nuclear ribonucleoproteins in rat
      tissues.
AB  - Heterogeneous nuclear ribonucleoproteins bind to RNA as long as it is
      transcribed. Since their binding can be sequence-specific, it has been suggested
      that their expression in different tissues could vary depending on the specific
      mRNA processing requirements. In order to better establish this possibility we
      studied the presence of the heterogeneous nuclear ribonucleoproteins A1, A2/B1, C
      and D in the cell nuclei of different rat tissues by one- and two-dimensional
      immunoblotting. We found that these proteins were heterogeneously distributed
      among tissues and that they were found in different proportions.

PMID- 7503736
TI  - D-glucose metabolism in cross-linked pancreatic islets.
AB  - D-glucose metabolism was investigated in pancreatic islets that underwent cross
      linking of intracellular proteins by dimethyl suberimidate. Both the utilization
      of D-[5-3H]glucose and oxidation of D-[U-14C]glucose were much more severely
      affected at high (16.7 mM) than at low (2.8 mM) concentration of the hexose, when
      comparing cross-linked to control islets. The preferential stimulation of D-[U
      14C]glucose oxidation relative to D-[5-3H]glucose utilization, resulting from an
      increase in hexose concentration, was not abolished, however, in cross-linked
      islets. Likewise, the activation of phosphofructokinase in glucose-stimulated
      islets did not appear to be impaired in cross-linked islets, the islet content in
      tritiated acidic metabolites generated from D-[5-3H]glucose failing to be
      increased in cross-linked islets. It is proposed, therefore, that the impaired
      responsiveness of cross-linked islets to a rise in D-glucose concentration might
      be attributable to an altered regulation of glucokinase, as possibly resulting
      from a missing interaction of the enzyme with GLUT-2.

PMID- 7503737
TI  - Calmodulin is involved in the induction of DNA polymerases alpha and delta
      activities in normal rat kidney cells activated to proliferate.
AB  - Normal rat kidney cells that reenter the cell cycle from quiescence start DNA
      synthesis at 12 h following serum addition and reach a maximum after 20 h. We
      have previously shown that the activation of DNA polymerase alpha, and the
      expression of the proliferating cell nuclear antigen were inhibited when the anti
      calmodulin drug W13 is added to the cell cultures. Here we have analyzed the
      effect of W13 on the activity of DNA polymerase delta and on the expression of
      replication protein A. The results showed that the blockade of calmodulin by W13
      produced an almost complete inhibition of DNA polymerase delta activity whereas
      the activity of DNA polymerase alpha was only partially inhibited. Finally, the
      expression of replication protein A was not affected after W13 treatment. Our
      data suggest that calmodulin might regulate DNA replication through the control
      of the activities of DNA polymerases alpha and delta and the expression of
      proliferating cell nuclear antigen.

PMID- 7503738
TI  - The pulmonary epithelial cell line L 2 as a new model for an inducible nitric
      oxide synthase expressing distal airway epithelial cell.
AB  - Nitric oxide released in large amounts by inducible nitric oxide synthase (iNOS)
      containing pulmonary cells plays an important role in many aspects of lung
      function in health and disease. The aim of this study was to establish a
      permanent non tumor-derived alveolar epithelial cell line that exhibits the
      typical characteristics of an iNOS-expressing cell. Therefore, the pulmonary
      epithelial cell line L2 (adult rat) was incubated with lipopolysaccharide derived
      from Escherichia coli (serotype 0111:B4) and different cytokines. The strongest
      effect on iNOS gene expression and nitric oxide release could be detected when L2
      cells were coincubated with interferon-gamma + tumor necrosis factor-alpha. iNOS
      complementary DNA concentration was 25 amol/microliters at 9h, and
      nitrite/nitrate levels were 99.43 +/- 3.97 nmol/10(6) cells at 24h, respectively.
      Our results show that L2 cells can be regarded as an appropriate model for
      investigating iNOS gene expression and nitric oxide functions in alveolar
      epithelial cells.

PMID- 7503740
TI  - Effects of nucleotide on skeletal muscle myosin unfolding in myofibrils by DSC.
AB  - The thermal unfolding of myosin in skeletal muscle myofibrils was studied by
      differential scanning calorimetry (DSC). In the absence of nucleotide two major
      transitions with Tm of 52 degrees C and 58 degrees C, and a minor transition with
      Tm of 19 degrees C were detected. The unfolding can be characterized with a total
      enthalpy of -90 +/- 6.1 mJ/g protein. The major transition with Tm of 58 degrees
      C was independent of the presence of nucleotide and orthovanadate (Vi), and it
      can be assigned to the unfolding of the alpha-helical rod part of myosin and
      partly to actin. In the presence of MgADP, the minor transition shifted to higher
      temperature, indicating changes between the heavy chain of subfragment-1 and the
      LC-2 light chain. The transition with Tm of 52 degrees C exhibited a significant
      broadening and a small shift to lower temperature. It indicates an internal
      domain or segmental rearrangement of the myosin motor. Upon addition of MgADP and
      Vi, a shift to higher temperature was observed for the lower major transition,
      evidencing that with trapped ADP and Vi the intermolecular interactions
      stabilized the myosin head region.

PMID- 7503739
TI  - Nitric oxide (nitrogen monoxide, NO) stimulates insulin secretion by inducing
      calcium release from mitochondria.
AB  - Nitric oxide (nitrogen monoxide, NO) acts as messenger molecule in a variety of
      cells and may also be involved in the insulin secretory pathway of islet beta
      cells. We report here that NO at a low micromolar concentration stimulates
      epinephrine-sensitive insulin secretion from cells of the beta-cell line, INS-1.
      Insulin secretion is paralleled by a reversible decrease of the mitochondrial
      membrane potential and by an increase of the cytosolic calcium. Chelation of
      intracellular, but not of extracellular calcium prevents the NO-induced insulin
      secretion. These data indicate that NO can stimulate insulin secretion by
      deenergizing mitochondria and thereby triggering mitochondrial calcium release.

PMID- 7503741
TI  - The loss of 40-kDa chromosomal protein in tuberous sclerosis lesions.
AB  - Tuberous sclerosis is an genetic disease characterized by systemic hamartomas.
      Some of the cultured cells derived from tuberous sclerosis show the distinct
      chromosomal disarrangement and abnormal cell division. To detect the proteins
      responsible for this phenomenon, we investigated many nuclear components related
      to cell division. 40-kDa protein (p40) recognized by one monoclonal antibody
      M108, which was present in nucleus, chromosomes and cytoplasm of many vertebrate
      culture cells, significantly decreased in the tuberous sclerosis cells.
      Immunoblot analysis revealed that in all the fractions the quantity of p40 of
      severe tuberous sclerosis cells was approximately 4 times less than p40 in normal
      fibroblasts.

PMID- 7503742
TI  - The association of the C-terminal region of beta I sigma II spectrin to brain
      membranes is mediated by a PH domain, does not require membrane proteins, and
      coincides with a inositol-1,4,5 triphosphate binding site.
AB  - The beta spectrin genes each produce two alternate transcripts the longer of
      which has a approximately 210 amino acid C-terminal extension including a
      pleckstrin homology (PH) domain and also an uncharacterized membrane binding
      site. GST constructs including the entire or the N-terminal segment of the beta I
      sigma II spectrin PH domain bind to crude and extracted brain membranes, to
      protein free brain lipid and to vesicles containing phosphatidylinositol-4,5
      bisphosphate. This PH domain also binds radiolabelled inositol-1,4,5
      trisphosphate (IP3) and preincubation with IP3 inhibits binding to extracted
      brain membranes. We conclude that membrane binding of the beta I sigma II
      spectrin C-terminal region is by means of a direct interaction between the N
      terminal region of the PH domain and membrane lipids and does not require
      membrane protein. The PH domain of the beta-adrenergic receptor kinase showed
      different binding properties in every assay employed, showing that different PH
      domains may have different membrane binding specificity.

PMID- 7503743
TI  - Allosteric activation of rabbit reticulocyte guanine nucleotide exchange factor
      activity by sugar phosphates and inositol phosphates.
AB  - Sugar phosphates are required to maintain active rates of translation in gel
      filtered rabbit reticulocyte lysates. They may stimulate polypeptide chain
      initiation by acting as NADPH generators or by a direct interaction with
      initiation factor(s). We now provide evidence for the allosteric activation of
      the purified guanine nucleotide exchange factor (eIF-2B) by sugar phosphates and
      inositol phosphates. In the presence of microM fructose 1,6-bisphosphate, the
      rate of eIF-2B-catalyzed GDP/GTP exchange is increased approximately 2-fold. The
      half-maximal concentration for stimulation of eIF-2B activity (SC50) is 57
      microM. The binding of GTP to isolated eIF-2B is stimulated 1.5-fold, whereas GTP
      binding to ALP-treated eIF-2B is not affected by sugar phosphates. Inositol 1,4
      bisphosphate, like fructose 1,6-bisphosphate, stimulates 2-3-fold the activity of
      the isolated eIF-2B (SC50, 140 microM).

PMID- 7503744
TI  - Procathepsin L degrades extracellular matrix proteins in the presence of
      glycosaminoglycans in vitro.
AB  - The processing of procathepsin L on the surfaces of physiological
      glycosaminoglycans, heparan sulfate, chondroitin sulfate, etc., as well as
      dextran derivatives were studied. All glycosaminoglycans and dextran derivatives
      including dextran T-500 and DEAE dextran examined in this study accelerated the
      conversion of procathepsin L to processed cathepsin L in vitro with different
      time courses. Further, we examined whether procathepsin L digests protein
      substrates in the presence or absence of the surface materials. Laminin was
      degraded by both procathepsin L itself and the 31-kDa processed form in the
      presence of surface materials with the same profiles. In contrast, fibronectin
      was digested by procathepsin L without processing in the presence of surface
      materials. The proteolytic profiles of fibronectin by the processed form differed
      from those by procathepsin L. This is the first evidence that the proform of a
      cysteine proteinase proteolyzes protein substrates.

PMID- 7503745
TI  - Determination of N-myristoyl peptide sequence both by MALDI TOF MASS and with an
      N-myristoyl cleaving enzyme (polymyxin acylase).
AB  - Polymyxin acylase isolated from Pseudomonas sp. M-6-3 was used as an N-myristoyl
      cleaving enzyme in order to determine a part of the N-terminal amino acid
      sequence of N-myristoyl proteins. The enzyme hydrolyzed a number of N-myristoyl
      oligopeptides at various hydrolysis rates but not N-myristoyl proteins. The
      oncogenic protein (N-myristoyl-pp60c-src) was isolated from human colon
      adenocarcinoma cell line COLO 320DM by two-dimensional polyacrylamide gel
      electrophoresis. The protein was digested with trypsin and the resultant tryptic
      N-myristoyl tetrapeptide (N-myristoyl-Gly-Ser-Asn-Lys) was purified by HPLC and
      the structure was determined both by matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry (MALDI TOF MASS) and by a gas-phase protein
      sequencer before or after treatment with the polymyxin acylase. The results
      suggest that the N-myristoyl peptide sequence derived from N-myristoyl proteins
      was clearly determined by the combined use of MALDI TOF MASS and the N-myristoyl
      cleaving enzyme.

PMID- 7503746
TI  - Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not
      periosteal fibroblasts--correlation with prostaglandin upregulation.
AB  - Osteocytes are extremely sensitive to fluid shear stress, a phenomenon that may
      be related to mechanical adaptation of bone (FASEB J 9:441,1995). Here we
      examined the effect of pulsating fluid flow (PFF, 0.5 +/- 0.02 Pa, 5 Hz, 0.4
      Pa/sec) on the release of NO, in relation with upregulation of prostaglandin E2
      (PGE2). Chicken calvarial osteocytes, but not periosteal fibroblasts, as well as
      mouse calvarial cells responded to PFF with a rapid and transient 2 to 3-fold
      stimulation of NO release. The effect was maximal after 5 min and leveled off
      thereafter. PFF also stimulated PGE2 release. This effect was significant after
      10 min and continued throughout 60 min PFF treatment. Inhibition of NO release by
      NG-monomethyl-L-arginine prevented the effect of PFF on NO as well as PGE2
      release. These results suggest that NO is a mediator of mechanical effects in
      bone, leading to enhanced PGE2 release. They further strengthen the hypothesis
      that fluid flow through the osteocyte canalicular network provides the physical
      stimulus for mechanosensation in bone.

PMID- 7503747
TI  - Elevated calcium level induces calcium-dependent proteolysis of A-CAM (N
      cadherin) in heart--analysis by detergent-treated model.
AB  - Calcium overload induces cardiac muscle cell dysfunction in cardiovascular
      diseases. We investigated the effects of elevated calcium level on adherens
      junction-specific cell adhesion molecule (A-CAM). Incubation of Triton X-100
      treated canine heart homogenate in the presence of Ca2+ reduced the content of A
      CAM. Reduction in A-CAM requires milli-molar Ca2+ and was inhibited by protease
      inhibitors, leupeptin and calpeptin. Immunohistochemical observation revealed
      that m-calcium-activated neutral protease (m-CANP) was colocalized with A-CAM in
      intercalated disks. These data suggested that m-CANP proteolyzes A-CAM in
      response to calcium overload in cardiac muscle.

PMID- 7503748
TI  - Activation of protein kinase C by oxidized diacylglycerols.
AB  - The effects of 1,2-diacylglycerol hydroperoxide (DAG-OOH), its alcohol (DAG-OH),
      "unoxidized" 1,2-diacylglycerol (DAG), 1,2-dioleoylglycerol (DOG), and phorbol 12
      myristate acetate (PMA) on the activity of protein kinase C (PKC) isolated from
      rat brain were examined in the presence and absence of phosphatidylserine (PS)
      and calcium ion. Both DAG-OOH and DAG-OH stimulated the activity of PKC dose- and
      time-dependently. The ability of additives for PKC activation increased in the
      order of DOG, DAG << DAG-OOH, DAG-OH < PMA. DAG-OOH and DAG-OH activated PKC even
      in the absence of PS and calcium ion as PMA does. If DAG-OOH and DAG-OH are
      released from the oxidized biomembranes by the action of phospholipase C, these
      components may act like PMA and serve to activate the PKC-dependent signal
      transduction system.

PMID- 7503749
TI  - Molecular cloning of a novel macrophage maturation-associated transcript encoding
      a protein with several potential transmembrane domains.
AB  - Differentiation of tissue macrophages from bone marrow progenitor cells via
      circulating blood monocytes is a complex and multistep process. In order to
      analyze macrophage maturation on the molecular level we used the method of mRNA
      differential display to identify novel genes that are preferentially expressed in
      mature, in vitro differentiated macrophages. A PCR-fragment could be isolated
      that was amplified from macrophages, but not from freshly isolated monocytes, and
      macrophage-specific expression was confirmed by Northern blot analysis. Several
      corresponding cDNA clones could be isolated from a macrophage cDNA library,
      covering a nucleotide sequence of 2.5 kb. Nucleotide sequence of this cDNA showed
      no homology to known genes. The sequence reveals an open reading frame that codes
      for a 238 amino acid hydrophobic protein with seven potential transmembrane
      domains, suggesting a possible role as a receptor or an ion channel.

PMID- 7503750
TI  - Age-associated changes of mitochondrial translation and respiratory function in
      mouse brain.
AB  - We examined age-associated changes of respiratory enzyme activities and protein
      synthesis in mitochondria isolated from mouse brain with high oxidative
      activities. Cytochrome c oxidase activity increased unexpectedly with aging,
      while the mitochondrial translational activities showed two phases of
      alterations: they increased progressively up to 21 weeks after birth followed by
      a gradual decrease with aging. Results showed that these changes were not due to
      the change in mitochondrial DNA (mtDNA) copy number or the accumulation of
      deletion mutations in mtDNA. These observations suggest that the common feature
      of age-associated changes in both human and mouse mitochondrial functions is
      limited to the decrease in mitochondrial translational activity. Therefore, mouse
      brain can be used as a model to understand the relationships between aging and
      mitochondrial function by examining the cause of decrease in mitochondrial
      translation activity.

PMID- 7503751
TI  - Expression of recombinant human Met-ase-1: a NK cell-specific granzyme.
AB  - Human Met-ase-1 is a member of a family of cytotoxic lymphocyte serine proteases
      (granzymes), but is expressed specifically in CD3- large granular lymphocytes
      with natural killer cell activity. We have devised a polymerase chain reaction
      strategy to delete the predicted hexapropeptide of human Met-ase-1 (Ser-6 to Gln
      1), to enable its expression and activation in mammalian COS cells. In addition,
      using peptide immunization we have derived a unique and specific monoclonal
      antibody detecting human Met-ase-1. Western blot analysis and protease assays of
      transfected COS cell lysates against a panel of thiobenzyl ester substrates
      formally demonstrated that the human Met-ase-1 gene encodes a serine proteinase
      that specifically hydrolyzes substrates containing a methionine (Met-) side chain
      at P1. The expression of active human Met-ase-1 and the generation of a specific
      anti-human Met-ase-1 monoclonal antibody will now enable a detailed
      structure/function analysis of key amino acids that confer this unusual serine
      protease specificity.

PMID- 7503752
TI  - The lumQ gene is linked to the lumP gene and the lux operon in Photobacterium
      leiognathi.
AB  - The nucleotide sequence of the designated lumQ gene (EMBL accession No. U35231)
      from Photobacterium leiognathi PL741 has been determined, and the encoded amino
      acid sequence is deduced. The LumQ protein has a calculated M(r) of 28,416 and
      comprises 248 amino acid residues. The lumQ gene is identified as the envY-like
      gene by significant similarity of the encoded protein with the EnvY and AdiY
      proteins of E. coli; there the envY gene encodes the porin thermoregulatory
      protein EnvY, and the adiY gene encodes the putative transcriptional regulator
      protein AdiY. It suggests that the lumQ gene of P. leiognathi is orthologous to
      the envY and adiY genes of E. coli. The function of the protein encoded by the
      lumQ gene from P. leiognathi is not really defined yet, it is likely to be the
      DNA-binding protein related to the araC and xylS family of transcriptional
      regulators. The lumQ and lumP genes form the lum operon which linked to the lux
      operon, but run in the opposite direction. The gene order of the lum and the lux
      operon is < -ter-lumQ-lumP-R&R-luxC-luxD-luxA-luxB- luxN-luxE- > (R&R: regulatory
      region; ter: transcriptional terminator); whereas the regulatory region (R&R)
      includes two promoter systems, PR-promoter for the lux operon and PL-promoter for
      the lum operon; ter is the transcriptional terminator of the lum operon.

PMID- 7503753
TI  - Developmental and tissue distribution of expression of nonmuscle and smooth
      muscle isoforms of myosin light chain kinase.
AB  - Using a combination of Northern and Western blotting and RT-PCR, we demonstrate
      the existence of a high molecular mass MLCK, which is expressed during chicken
      embryogenesis. It is expressed in developing smooth muscle containing tissues,
      and is detected at low concentrations in adult tissues. Direct sequencing of the
      RT-PCR product from embryonic tissue RNA revealed that the embryonic, high
      molecular mass MLCK is indeed the previously cloned "nonmuscle MLCK". Therefore,
      the high molecular mass MLCK should be termed embryonic/non-muscle MLCK isoform.
      Curiously, cultured embryonic gizzard and vascular smooth muscle cells express
      the lower molecular mass smMLCK protein, albeit at lower levels than in the in
      vivo tissues.

PMID- 7503754
TI  - Cyclooxygenase-2: regulation and relevance in inflammation.

PMID- 7503755
TI  - Properties of the reversible K(+)-competitive inhibitor of the gastric (H+/K+)
      ATPase, SK&F 97574. I. In vitro activity.
AB  - SK&F 97574 (3-butyryl-4-(2-methylamino)-8-(2-hydroxyethoxy)quinoline), is a
      potent inhibitor of the (H+/K+)-ATPase in membrane vesicles isolated from porcine
      gastric mucosa. It inhibits (H+/K+)-ATPase activity in lyophilised vesicles in a
      kinetically competitive manner with respect to the activating cation, K+, with an
      inhibition constant (Ki) of 0.46 +/- 0.003 microM. Inhibition of (H+/K+)-ATPase
      activity is freely reversible. Binding of SK&F 97574 was shown to be mutually
      exclusive and the previously reported reversible (H+/K+)-ATPase inhibitors, SCH
      28080 and MDPQ. Therefore, despite its structural dissimilarity, SK&F 97574
      appears to bind to the same lumenal region of the (H+/K+)-ATPase identified as
      the binding site for these compounds. SK&F 97574 is a weak base (pKa = 6.86), and
      would therefore be expected to accumulate in the acidic compartment at the
      lumenal face of the parietal cell. In intact gastric vesicles (which have the
      lumenal face of the ATPase on the interior), SK&F 97574 inhibited ATP-dependent
      H(+)-transport with a similar potency to ATPase activity. SK&F 97574 is therefore
      relatively membrane permeable, and would be predicted to gain access readily to
      its site of action in vivo. The effect of pH on inhibition of H+/K(+)-ATPase
      activity by SK&F 97574 is consistent with its being active only in its protonated
      form. The selectivity of SK&F 97574 for the gastric (H+/K+)-ATPase was tested by
      examining its ability to inhibit a closely related p-class pump, the (Na+/K+)
      ATPase from dog kidney. SK&F 97574 was found to have a 60-fold greater
      sensitivity for the former enzyme. The (Na+/K+)-ATPase was not inhibited in a
      K(+)-competitive manner by SK&F 97574, indicating an entirely different, probably
      nonspecific, mechanism.

PMID- 7503756
TI  - Properties of the reversible, K(+)-competitive inhibitor of the gastric (H+/K+)
      ATPase, SK&F 97574. II. Pharmacological properties.
AB  - SK&F 97574 [3-Butryl-4-(2-methylamino)-8-(2-hydroxyethoxy) quinoline] is a
      potent, reversible inhibitor of the gastric (H+/K+)-ATPase. In an anaesthetised
      lumen-perfused rat preparation, it inhibited pentagastrin-stimulated gastric acid
      secretion with intravenous and intraduodenal inhibitory ED50 values of 2.40
      mumol/kg and 4.43 mumol/kg, respectively. In the conscious fistula rat model,
      doses of 10 mumol/kg IV and 25 mumol/kg PO produced mean peak inhibitions of
      basal acid output of 91% and 97%, respectively. In these experiments, the
      duration of action of SK&F 97574 was much shorter than that of the covalent
      (H+/K+)-ATPase inhibitor, omeprazole. In the conscious Heidenhain pouch dog, SK&F
      97574 inhibited histamine-stimulated gastric acid secretion after both
      intravenous and oral administration with ED50 values of 0.49 mumol/kg and 0.89
      mumol/kg, respectively. In this model, duration of action studies showed that
      significant residual inhibition of acid secretion remained 8 hours after
      intravenous dosing with SK&F 97574 (producing peak inhibition of 92%). However,
      24 hours after oral dosing of SK&F 97574 (10 mumol/kg), no significant inhibition
      remained. These data indicate that the duration of action of SK&F 97574 is longer
      than that of the histamine H2 receptor antagonists such as cimetidine, but
      shorter than that of covalent (H+/K+)-inhibitors such as omeprazole. Overall, the
      pharmacological properties of SK&F 97574 suggest that it could be a potentially
      useful clinical treatment for acid-related diseases.

PMID- 7503757
TI  - Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat.
AB  - Parameters related to hepatic oxidative stress, cell injury, phagocytic activity,
      and liver histology were studied in control rats and in animals subjected to L
      3,3',5-triiodothyronine (T3) and/or lindane administration. Hyperthyroidism
      elicited a calorigenic response and increased rates of hepatic O2 uptake, which
      were not modified by lindane treatment. T3 diminished serum lindane levels as
      well as those in the liver and adipose tissue, whereas lindane enhanced serum T3
      levels in animals given T3. Compared with control rats, lindane significantly
      increased the rate of formation of thiobarbituric acid reactants (TBARS) by the
      liver, with no changes in either the reduced glutathione (GSH) content, the
      TBARS/GSH ratio as indicator of oxidative stress, or in the fractional rates of
      lactate dehydrogenase (LDH) and GSH efflux from perfused livers as integrity
      parameters. Hyperthyroidism induced GSH depletion in the liver, with a
      significant enhancement in the TBARS formation, the TBARS/GSH ratio, and in the
      fractional LDH and GSH efflux. These parameters were increased further by joint
      T3 and lindane administration in a magnitude exceeding the sum of the effects
      produced by the separate treatments. In addition, hyperthyroidism led to Kupffer
      cell hyperplasia and significant increases in serum glutamate oxalacetate
      transaminase (GOT) and in hepatic zymosan-induced chemiluminescence, while liver
      myeloperoxidase (MPO) activity was found unchanged, compared with controls. Rats
      treated with lindane presented normal liver histology, with no changes in
      biochemical parameters related to cell injury. The joint administration of T3 and
      lindane, however, elicited a marked elevation in serum GOT and glutamate pyruvate
      transaminase (GPT), concomitantly with extensive liver necrosis and the presence
      of granulomas containing lymphocytes, Kupffer cells and polymorphonuclear
      leukocytes (PMN). In this condition, hepatic zymosan-induced light emission and
      MPO activity were enhanced over control values. It is concluded that
      hyperthyroidism increases the susceptibility of the liver to the toxic effects of
      lindane, which seems to be accomplished by potentiation of the hepatic oxidative
      stress status. The latter effect may be conditioned by an enhanced phagocytic
      respiratory burst activity due to the observed Kupffer cell hyperplasia and PMN
      infiltration, in addition to the increased production of reactive oxygen species
      in parenchymal cells.

PMID- 7503758
TI  - 4-Ipomeanol and 2-aminoanthracene cytotoxicity in C3H/10T1/2 cells expressing
      rabbit cytochrome P450 4B1.
AB  - In the present study, retroviral vectors were used to stably transfer and express
      the cDNA encoding rabbit CYP4B1 in mouse C3H/10T1/2 cells. The replication
      defective retroviral vector was packaged in the ecotropic packaging cell line,
      GP+E-86, with infectious titer of approximately 1 x 10(6) cfu/mL. Infection,
      followed by selection with G418, showed an infection efficiency of approximately
      70% for the recipient C3H/10T1/2 cells. Analysis of ten G418 resistant clones
      showed that the number of vector inserts ranged from 4 to 13 copies per cell
      genome. Each clone was positive for microsomal CYP4B1 protein as determined by
      immunoblotting. Cytochrome P450 4B1 activity was assessed by the cytotoxicity of
      4-ipomeanol, a known substrate for P450 4B1 and a model compound for chemical
      induced injury to the lung. The initial clonigenic assays showed that 100%
      toxicity occurred in all the clones after a 96-hr exposure to 250 microM 4
      ipomeanol. Parental C3H/10T1/2 cells were resistant to 4-ipomeanol at
      concentrations as high as 1 mM. Two clones, designated No. 2 and No. 19,
      differing in levels of P450 4B1 protein, were characterized further for 4
      ipomeanol and other chemical toxicities. A concentration-response study indicated
      50% cytotoxicity at 4-ipomeanol concentrations of 1.5 micrograms/mL for clone No.
      2 and 2.5 micrograms/mL for clone No. 19. A panel of agents representing the
      aromatic amines, some of which are known or suspected P450 4B1 substrates, were
      tested for cytotoxicity in clone No. 2. These agents included 2-aminoanthracene,
      2-aminonaphthalene, 2-aminofluorene, 2-acetylaminofluorene and 4-aminobiphenyl.
      Only 2-aminoanthracene gave a clear cytotoxic response reducing the survival
      fraction of clone No. 2 to 50% at 0.2 micrograms/mL while affecting parental
      cells minimally. In vitro expression of CYP4B1 provides a new experimental system
      for further elucidating the cytotoxic and mutagenic effects of P450 4B1
      substrates.

PMID- 7503759
TI  - Characterization of a novel potent and specific inhibitor of type V
      phosphodiesterase.
AB  - Guanosine cyclic 3':5'-monophosphate (cGMP) plays a crucial role in regulating
      vascular smooth muscle contractile state. In rat aortic smooth muscle cells
      (RSMC) three isozymes of phosphodiesterase (PDE) may be involved in the
      degradation of cGMP, namely PDE I, PDE III, and PDE V. To study the effective
      contribution of PDE V to the control of intracellular cGMP levels, a specific and
      potent PDE V inhibitor 1,3-dimethyl-6-(2-propoxy-5
      methanesulfonylamidophenyl)pyrazolo[3, 4d]- pyrimidin-4-(5H)-one (DMPPO) was
      synthesized. DMPPO is a competitive inhibitor with respect to cGMP (Ki = 3 nM)
      and displayed high selectivity for PDE V as compared to other PDE isozymes. DMPPO
      strongly potentiated the cGMP response of atrial natriuretic peptide- or sodium
      nitroprusside-treated RSMC (EC50 = 0.5 microM). In addition, similar
      intracellular cGMP levels were obtained in the presence of a saturating
      concentration of DMPPO or 3-isobutyl-1-methylxanthine, a nonspecific PDE
      inhibitor, suggesting that cGMP is almost exclusively hydrolyzed by PDE V in
      RSMC. Stimulation of RSMC with atrial natriuretic factor resulted in accumulation
      of cGMP in the extracellular media. This egression was shown to be proportional
      to the intracellular level of cGMP and a first-order rate constant of 0.04 min-1
      was determined for the egression process. DMPPO did not interfere with the efflux
      and allowed us to show that intracellular cGMP levels are mainly controlled by
      PDE V, rather than by egression in RSMC. DMPPO is, therefore, a useful tool for
      determining the role of PDE V in the control of cGMP levels in living cells and
      tissues.

PMID- 7503760
TI  - Production of adenosine and nucleoside analogs by the exchange reaction catalyzed
      by rat liver adenosine kinase.
AB  - We have previously shown [8] that rat liver adenosine kinase can produce [14C]AMP
      from [14C]adenosine (Ado) and unlabelled adenosine monophosphate (AMP), in the
      absence of ATP, by an exchange reaction. In this study, we investigated whether
      Ado or AMP could be replaced in this exchange reaction by other nucleosides or
      nucleoside monophosphates (NMP), respectively. In the presence of 1 mM of the
      unlabelled NMP analogs 7-deazaadenosine (tubercidin) 5'-monophosphate, 6
      chloropurine riboside 5'-monophosphate, or N6-methyl-AMP, [14C]AMP was formed
      from 20 microM [14C]Ado at up to 50% of the rate recorded with 1 mM unlabelled
      AMP. In the presence of 0.2 mM of the unlabelled analog nucleosides tubercidin,
      N6-methyladenosine, or 6-methylmercaptopurine riboside, [14C]Ado was generated
      from 1 mM [14C]AMP at up to 60% of the rate recorded with 0.2 mM unlabeled Ado.
      Small amounts of [14C]Ado were also formed from the natural nucleosides 5-amino-4
      imidazolecarboxamide (AICA) riboside or 2'-deoxyadenosine. Administration of
      therapeutic anticancer and antiviral nucleosides that can serve as substrates for
      the exchange reaction catalyzed by adenosine kinase might, thus, result in a net
      production of Ado, a potent autacoid with physiological effects in numerous
      tissues.

PMID- 7503761
TI  - Expression of rat microsomal epoxide hydrolase during pregnancy.
AB  - Microsomal epoxide hydrolase (mEH) protein and messenger ribonucleic acid (mRNA)
      levels were assessed in maternal rats during pregnancy and mEH gene expression
      was compared with cytochrome P450 expression. Immunoblot analysis using goat anti
      rat mEH antibody showed that hepatic mEH levels in adult rats at day 12 of
      gestation were comparable to those in virgin female rats at the same age, whereas
      mEH protein levels were substantially decreased by approximately 70% at day 20 of
      pregnancy. Northern and slot blot analyses revealed that hepatic mEH mRNA levels
      failed to be modulated at day 12 of pregnancy, whereas mEH mRNA levels were
      decreased to approximately 20% of virgin control in late pregnancy (i.e. day 20),
      which was consistent with the result of mEH immunoblot analysis. Hepatic
      cytochrome P4502E1 levels were also diminished at day 12 and day 20 of gestation
      by approximately 50% and approximately 70%, respectively, relative to virgin
      control rats, as supported by immunoblot analysis. Hepatic P4502E1 mRNA levels at
      day 12 and day 20 of pregnancy were also significantly decreased to 30% and 8% of
      virgin rats at 17 weeks of age, respectively, demonstrating that suppression in
      P4502E1 protein levels accompanied decreases in its mRNA expression. The levels
      of cytochrome P4501A2 mRNA at either day 12 or day 20 of pregnancy was decreased
      by approximately 50% relative to virgin female rats, which was less than that
      observed in mEH or P4502E1 expression. Pregnancy failed to affect P4501A1 mRNA
      levels, which were not detectable in female rats at 17 weeks of age. Renal mEH
      mRNA levels in maternal rats at day 20 of gestation were also decreased to 25% of
      virgin control. These results demonstrated that levels of mEH and P4502E1
      proteins decreased significantly in late pregnancy with concomitant decreases in
      their mRNA levels.

PMID- 7503762
TI  - The antianginal agent ranolazine is a weak inhibitor of the respiratory complex
      I, but with greater potency in broken or uncoupled than in coupled mitochondria.
AB  - Ranolazine (RS-43285) has shown antianginal effects in clinical trials and
      cardiac anti-ischaemic activity in several in vivo and in vitro animal models,
      but without affecting haemodynamics. Its mechanism is thought to mainly involve a
      switch in substrate utilisation from fatty acids to glucose to, thus, improve
      efficiency of O2 use; however, its precise molecular target(s) are unknown. In
      studies to investigate its action further, using isolated rat heart mitochondria,
      ranolazine was found to weakly inhibit (pIC50 values > 300 microM) respiration by
      coupled mitochondria provided with NAD(+)-linked substrates but not with
      succinate. With broken mitochondrial membranes or submitochondrial particles,
      ranolazine inhibited NADH but not succinate oxidation and with pIC50 values in
      the lower range of 3-50 microM. Studies with different electron acceptors and
      respiratory inhibitors indicated that it inhibits respiratory Complex I at a site
      between ferricyanide and menadione and ubiquinone-1 reduction (i.e. at a similar
      locus to rotenone). However, unlike rotenone, ranolazine was an uncompetitive
      inhibitor with respect to ubiquinone-1. Ranolazine inhibition of Complex I was
      reversible and occurred also with mitochondria from pig, guinea pig, and human
      heart, and rat liver. Further studies using rat heart mitochondria in different
      energisation states (i.e. broken, uncoupled, or coupled) showed a 50-100-fold
      shift to greater potency of ranolazine in the broken compared to the coupled;
      with the uncoupled it was about 2-fold less potent than the broken. These shifts
      in potency were not found with rotenone or amytal. Studies with radiolabelled
      ranolazine showed that it bound to mitochondrial membranes with greater affinity
      in the broken compared to the coupled or uncoupled conditions. Rotenone displaced
      radiolabelled ranolazine from its binding site. This property of ranolazine may
      play some role in its anti-ischaemic activity.

PMID- 7503763
TI  - Iron-stimulated ring-opening of benzene in a mouse liver microsomal system.
      Mechanistic studies and formation of a new metabolite.
AB  - In the present study, we investigated the mechanism(s) of ring-opening of benzene
      in a mouse liver microsomal system in the presence of Fe2+.HPLC analysis based on
      coelution with authentic standards and on-line UV spectra obtained using a diode
      array detector indicated that benzene is metabolized to phenol, hydroquinone
      (HQ), trans,trans-muconaldehyde (muconaldehyde, MUC), 6-oxo-trans,trans-2,4
      hexadienoic (COOH-M-CHO), 6-hydroxy-trans,trans-2,4-hexadienal (CHO-M-OH), and 6
      hydroxy-trans,trans-2,4-hexadienoic acid (COOH-M-OH). CHO-M-OH was confirmed by
      mass spectrometry. Muconaldehyde was also metabolized to CHO-M-OH, COOH-M-CHO and
      COOH-M-OH, in the same microsomal system. The inhibition of muconaldehyde
      metabolism by microsomes in the presence of pyrazole indicates that there is
      cytosolic alcohol dehydrogenase (ADH) activity in the microsomes. Metabolism by
      contaminating ADH of muconaldehyde formed during microsomal incubation of benzene
      could be involved in the formation of CHO-M-OH and COOH-M-OH. The ring-opening of
      benzene was stimulated by added Fe2+. Hydrogen peroxide was produced in the
      microsomal system and consumed in the presence of added Fe2+. Addition of
      catalase inhibited the formation of ring-opened products, while superoxide
      dismutase increased their formation in the presence of azide. Singlet oxygen
      scavengers, i.e. histidine, deoxyguanosine, Tris and azide (at concentrations
      above 1.0 mM), dramatically decreased the ring-opening of benzene. Hydroxyl
      radical scavengers, DMSO, mannitol and formate, but not ethanol, also decreased
      the ring-opening of benzene. The data indicate that Fenton chemistry plays an
      important role in benzene ring-opening by microsomes. An unknown peak with UV
      absorption maxima at 275 and 345 nm was also detected. Based on pH sensitivity of
      the UV spectrum, the reactivity with thiobarbituric acid (giving a chromogen with
      absorption maximum at 532 nm) and the molecular weight (126), this compound was
      identified tentatively as alpha- or beta-hydroxymuconaldehyde.

PMID- 7503764
TI  - An autoradiographical saturation kinetic study of the different benzodiazepine
      binding sites in rat brain by using [3H] flunitrazepam as a radioligand.
AB  - The present study reports on the equilibrium association constant (KD) and
      receptor density (Bmax) values of a number of brain areas from the mesencephalon,
      cerebral cortex, hippocampus, and cerebellum for the overall benzodiazepine (BZ)
      binding sites as well as for benzodiazepine binding site subtype 1 (BZ1) and
      subtype 2 (BZ2), determined by autoradiographical procedures using [3H]
      flunitrazepam. The differences between BZ1 and BZ2 binding sites were analyzed
      using the specific BZ1 agonist zolpidem as inhibitor of the radioligand.
      Statistically significant differences in the affinities of BZ2 with respect to BZ
      and BZ1 binding site were mainly found in cortical layers when pKD (negative
      logarithms of KD values) values were compared (ANOVA-SNK test). The distribution
      of Bmax, as well as the percentages of BZ1 and BZ2 and Hill coefficients which,
      surprisingly, are always close to 1 (> 0.9) for all the saturation kinetics
      analyzed, are also described. The possibility of heterogeneity related to
      anatomical distribution in the different subtypes is discussed.

PMID- 7503765
TI  - Thyronines and probucol inhibition of human capillary endothelial cell-induced
      low density lipoprotein oxidation.
AB  - Oxidized lipoproteins have been implicated as important factors in the
      pathogenicity of atherosclerosis. Thus, antioxidants play a significant role in
      inhibiting a critical step in atheroma progression. Previously, we demonstrated
      that thyronine analogs inhibit Cu(2+)-induced low density lipoprotein (LDL)
      oxidation. In the present study, we examined the effect of thyronine analogs on
      endothelial cell (EC)-induced LDL oxidation. LDL was incubated with or without EC
      in the presence or absence of various concentrations of thyronine, vitamin C, or
      probucol at 37 degrees in a humidified atmosphere (95% air, 5% CO2). Thyronine
      analogs, probucol, and vitamin C inhibited EC-induced LDL oxidation in a
      concentration-dependent manner. The concentration of each agent (microM)
      producing 50% inhibition (IC50) of EC-induced LDL oxidation for thiobarbituric
      acid reactive substances (TBARS) and electrophoretic mobility, respectively, was
      as follows: 0.294 and 0.417 for levothyroxine (L-T4); 0.200 and 0.299 for L
      triiodothyronine (L-T3); 0.125 and 0.264 for dextro-thyroxine (D-T4); 0.203 and
      0.304 for reversed triiodothyronine (rT3); 1.02 and 1.44 for probucol; and 13.6
      and 14.9 for vitamin C. Thyroid binding globulin (TBG) inhibited EC-induced LDL
      oxidation; further, thyronines bound to TBG exhibited more antioxidant activity
      than unbound thyronines. Pretreatment of EC with any of the thyronines decreased
      the ability of EC to oxidize LDL. Also, our results showed that a synergistic
      interaction exists between vitamin C and T4 in the inhibition of EC-induced LDL
      oxidation. The T4 and TBG concentrations that inhibited LDL oxidation were in the
      physiological range. We conclude that T4, like the pharmacological agent
      probucol, reduces oxidative modification of LDL and thus may act as a natural
      inhibitor of atherogenesis.

PMID- 7503766
TI  - The inhibitory effects of boldine, glaucine, and probucol on TPA-induced down
      regulation of gap junction function. Relationships to intracellular peroxides,
      protein kinase C translocation, and connexin 43 phosphorylation.
AB  - The naturally occurring antioxidant boldine and its di-methoxy analogue glucine,
      as well as the drug antioxidant probucol, all inhibit TPA-induced downregulation
      of gap junctional intercellular communication in WB-F344 rat liver epithelial
      cells in dose-dependent manners. The compounds were essentially 100% inhibitory
      to the effect of TPA (10 nM) at 50 microM each. Analysis of the mechanism of the
      antitumor promotive action of these agents in vitro revealed that boldine and
      probucol (both at 10 microM) totally inhibited the TPA-induced accumulation of
      intracellular oxidants. Additionally, boldine, glaucine, and probucol, each at 50
      microM, inhibited TPA-induced translocation of protein kinase C (PKC) to the
      particulate fraction of the cells, with concomitant inhibition of TPA-induced
      hyperphosphorylation of gap junctional connexin 43 (cx43) and TPA-induced
      internalisation of cx43 protein from the plasma membrane of the cells. None of
      the compounds inhibited the binding of (3H)-PDBu to TPA-specific binding sites in
      the cells. The results indicate that antioxidant molecules, irrespective of
      structure, possess common antitumor promotive potential in this model of gap
      junctional intercellular communication. The data also indicate that the compounds
      may interfere with the promotive function of TPA, at least in part, by the
      destruction of oxidants within the cells. Xanthine oxidase was excluded as a
      major source of such intracellular oxidants because allopurinol (50 microM) did
      not significantly affect either the accumulation of oxidants in the cells or the
      downregulation of gap junctional communication in response to TPA. Taken
      together, these data also suggest that TPA-induced oxidants play a role in the
      translocation of PKC to cellular membranes and it is at this level where the
      antioxidants may interfere in TPA-induced downregulation of gap junctional
      function.

PMID- 7503767
TI  - Possible pharmacokinetic and pharmacodynamic factors affecting parkinsonism
      inducement by cinnarizine and flunarizine.
AB  - Potentialities of cinnarizine [1-(diphenylmethyl)-4-(3-phenyl-2
      propenyl)piperazine, CZ] and its fluorine derivative flunarizine [1-[bis(4
      fluorophenyl)-methyl]-4-(3-phenyl-2-propenyl)piperazine, FZ] to induce
      parkinsonism as an adverse effect were evaluated pharmacokinetically and
      pharmacodynamically in rats. In multiple-dose experiments, CZ or FZ was given to
      rats at a daily dose of 20 mumol/kg for 1, 5, 10, 15, and 30 days, and CZ, FZ,
      and the ring-hydroxylated metabolites of their cinnamyl moiety [1
      (diphenylmethyl)-4-[3-(4'-hydroxyphenyl)-2-propenyl]piperazine, C-2 and 1-[bis(4
      fluorophenyl)methyl]-4-[3-(4'- hydroxyphenyl)propenyl]piperazine, F-2] in the
      plasma and striatum were determined 24 hr after the final dose. Plasma and
      striatum concentrations of the above compounds except for FZ reached steady state
      after 10 doses, but their concentrations of FZ continued to increase throughout
      the experiments. The concentrations obtained after the 30 doses were in the order
      of FZ > F-2 > CZ > C-2 for the plasma and of F-2 > FZ > CZ > C-2 for the
      striatum. The ratios of striatum to plasma concentrations of C-2 and F-2 were 2.4
      and 3 times higher than those of the parent drugs. Binding affinities of CZ, FZ,
      and their 10 metabolites for rat striatal dopamine D-2 receptors (D2-R) were
      assessed by competitive radioligand-binding studies using [3H]-N-[(2RS,3RS)-1
      benzyl-2-methyl-3-pyrrolidinyl]-5-chloro-2-met hoxy- 4-methylamino-benzamide
      ([3H]-YM-09151-2). The IC50s calculated from their Ki values were in the order of
      F-2 < C-2 < FZ < CZ < C-4 << F-1, indicating that C-2 and F-2 exhibit higher
      affinities for D2-R than the parent drugs, whereas affinities of other
      metabolites were 1 to 2 orders of magnitude less than those of C-2 and F-2. These
      results suggest some important roles of C-2 and F-2 in the development of
      parkinsonism as active metabolites during chronic medication with CZ and FZ,
      respectively.

PMID- 7503768
TI  - Differentiation between partial and silent 5-HT1D beta receptor antagonists using
      rat C6-glial and Chinese hamster ovary cell lines permanently transfected with a
      cloned human 5-HT1D beta receptor gene.
AB  - Intrinsic activities of serotonin (5-HT) receptor ligands at cloned human 5-HT1D
      beta receptor sites were determined by measuring cAMP responses in two
      permanently transfected cell types: rat C6-glial and Chinese hamster ovary (CHO)
      K1 cells. Both transfected cell lines expressed a similar 5-HT1D beta receptor
      density (361 to 448 fmol/mg protein) and displayed a number of similar cAMP
      responses: marked inhibition of forskolin-stimulated cAMP formation by 5-HT; a
      similar agonist potency and efficacy with 5-carboxamidotryptamine (5-CT), 5
      methoxytryptamine, bufotenine, sumatriptan, 7-trifluoromethyl-4(4-methyl-1
      piperazinyl)-pyrolo-(1,2-a)quinoxal ine (CGS 12066B), 5-methoxy-3(1,2,3,6
      tetrahydro-4-pyridinyl)1H-indole (RU 24,969), and tryptamine, their maximal
      effect being comparable to that of 5-HT; less agonist efficacy with m-trifluoro
      phenyl-piperazine (TFMPP) (it inhibited at most 63% of stimulated cAMP
      formation); and antagonist activity against the 5-CT-mediated agonist response
      with methiothepin, 2'-methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4
      carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR
      127,935), and ritanserin. Metergoline and 1-naphtylpiperazine showed different
      intrinsic activities. In contrast to their pronounced antagonist activity in the
      transfected CHO-K1 cell line, the antagonist effect was only partial and absent
      for metergoline and 1-naphtylpiperazine in the transfected C6-glial cell line,
      respectively. In conclusion, these cell lines are useful as a tool to measure
      with high sensitivity differences in intrinsic activities of 5-HT receptor
      ligands and, therefore, discriminate between silent antagonists (no intrinsic
      activity) and antagonists with intrinsic activity (i.e. partial agonists), even
      though this intrinsic activity may be relatively weak.

PMID- 7503769
TI  - Insulin-dependent suppression in glutamyl hydrolase activity and elevated
      cellular methotrexate polyglutamates.
AB  - Folates and antifolates are converted to polyglutamates, which are better
      retained in cells and may also bind more tightly to cellular proteins than the
      parent compounds. The regulation of the process of polyglutamate formation and
      breakdown is not fully clarified yet and is being studied by a number of
      approaches. An early observation concerning the potential regulation of
      polyglutamate formation was that insulin caused a marked increase in the rate and
      accumulation of polyglutamates of methotrexate (MTX) in rat hepatoma cells. The
      present study demonstrated that insulin caused a decrease in the activity of
      gamma-glutamyl hydrolase (GH), the enzyme that degrades polyglutamates, that was
      inversely commensurate with the increase in the synthesis of MTX polyglutamates.
      The effects of insulin on GH activity with regard to concentration, time of
      onset, and the effect of N6, O2' dibutyryl cAMP and theophylline were consistent
      with the reduction in GH being responsible for the increase in cellular MTX
      polyglutamate accumulation. Insulin addition also led to an increase in folate
      polyglutamates. The insulin effects were also seen with H35D cells, a subline
      with enhanced glutamyl hydrolase activity as a result of having been made
      resistant to 5, 10-dideazatetrahydrofolic acid. When H35 cells with insulin were
      compared with H35D cells lacking insulin, there was an 8-fold increase in GH and
      a 44-fold decrease in the number of gamma-glutamate residues added to MTX.

PMID- 7503770
TI  - Regulation of nicotinic acetylcholine receptors on human neuroblastoma cells
      during differentiation.
AB  - Neuronal nicotinic acetylcholine receptors are expressed on a variety of cells in
      the nervous system where they play key roles in synaptic transmission and
      information transfer. Little is known, however, about the molecular mechanisms
      that control their expression, distribution, and function during nervous system
      development. We have investigated the control of expression during
      differentiation of one class of acetylcholine receptors that bind alpha
      bungarotoxin of human neuroblastoma cells. We report that induction of
      differentiation of SH-SY5Y, SK-n-SH or IMR-32 cells by the phorbol ester 12-O
      tetradecanoyl phorbol 13-myristate (10 nM, TPA) or by retinoic acid resulted in
      as much as a 70% decline in alpha-bungarotoxin receptors on the cells. The
      response to the phorbol ester was blocked by the protein kinase C inhibitors
      staurosporine and bisindolylmaleimide. The decrease in receptors induced by 10
      microM retinoic acid was not affected by either agent. However, responses to
      lower (10 nM) concentrations of retinoic acid were blocked by staurosporine but
      not bisindolylmaleimide, suggesting a dual mechanism of action for retinoic acid
      in regulating acetylcholine receptors. It appears that acetylcholine receptors on
      neuroblastoma cells are regulated during differentiation by both protein kinase C
      dependent and -independent mechanisms.

PMID- 7503771
TI  - Susceptibility of idarubicin, daunorubicin, and their C-13 alcohol metabolites to
      transport-mediated multidrug resistance.
AB  - The intracellular pharmacokinetics and cytotoxicity of idarubicin (IDA),
      daunorubicin (DNR), and their corresponding C-13 alcohol metabolites,
      idarubicinol (IDAol) and daunorubicinol (DNRol), were studied in drug-sensitive
      HL-60/W human leukemia cells, and in two multidrug-resistant (MDR) sublines, HL
      60/Vinc (overexpress P-glycoprotein, Pgp) and HL-60/Adr (overexpress multidrug
      resistance-associated protein, MRP). Intracellular drug accumulation (1
      micrograms/mL) and retention were measured by flow cytometry. Mean intracellular
      steady-state concentration (Css, fluorescence units/cell) and area under the
      intracellular drug concentration x time curve (AUC, Fl.U/cell.min) were
      calculated. Relative to the values for the respective drugs in HL-60/W cells, the
      Css and AUC of IDA were much higher than those of DNR in the MDR cell lines, with
      Css and AUC of IDAol intermediate between IDA and DNR. In the MDR cell lines, the
      MDR modulator cyclosporine A (CsA), in concentrations of 0.3 to 30 mumol/L,
      caused minimal effects on 3-hr IDA accumulation, intermediate enhancement of
      IDAol accumulation, and greatest enhancement of DNR accumulation. The MDR cell
      lines were much less resistant to IDA (3- to 16-fold) than to DNR (65- to 117
      fold). This difference was not the result of IDA being more potent than DNR,
      since the sensitivity of HL-60/W cells to IDA differed from their sensitivity to
      DNR by < 2-fold. The cellular pharmacokinetics and cytotoxicity of IDA in MDR
      human breast carcinoma cells MCF-7/AdrVp, which overexpress the putative MDR
      transporter P-95, were far superior to those of DNR, and were comparable to these
      parameters for IDA in parental MCF-7/W cells. These studies demonstrate that the
      cellular pharmacology and cytotoxicity of IDA in MDR cell lines that overexpress
      MRP, Pgp, or P-95 are more advantageous than those of DNR, suggesting that IDA is
      less susceptible to the transport-mediated MDR mechanism manifested. IDA is not
      completely invulnerable to MDR, however, since the MDR sublines studied did
      display a demonstrable level of resistance to IDA, compared with their drug
      sensitive counterparts. IDAol, the major plasma metabolite of IDA, demonstrated
      behavior intermediate between the MDR-susceptible drug DNR and its parent
      compound, suggesting that its cytotoxic action is subject to transport-mediated
      cellular defenses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7503772
TI  - Structure-activity relationships for the binding of ligands to xanthine or
      guanine phosphoribosyl-transferase from Toxoplasma gondii.
AB  - Preliminary characterization of Toxoplasma gondii phosphoribosyltransferase
      activity towards purine nucleobases indicates that there are at least two enzymes
      present in these parasites. One enzyme uses hypoxanthine, guanine, and xanthine
      as substrates, while a second enzyme uses only adenine. Furthermore, competition
      experiments using the four possible substrates suggest that there may be a third
      enzyme that uses xanthine. Therefore, sixty-eight purine analogues and thirteen
      related derivatives were evaluated as ligands of T. gondii
      phosphoribosyltransferase, using xanthine or guanine as substrates, by examining
      their ability to inhibit these reactions in vitro. Inhibition was quantified by
      determining apparent Ki values for compounds that inhibited these activities by
      greater than 10% at a concentration of 0.9 mM. On the basis of these data, a
      structure-activity relationship for the binding of ligands to these enzymes was
      formulated using hypoxanthine (6-oxopurine) as a reference compound. It was
      concluded that the following structural features of purine analogues are required
      or strongly preferred for binding to both enzymes: (1) a pyrrole-type nitrogen
      (lactam form) at the 1-position; (2) a methine (= CH-), a pyridine type nitrogen
      (= N-), or an exocyclic amino or oxo group at the 2-position; (3) no exocyclic
      substituents at the 3-position; (4) an exocyclic oxo or thio group in the one or
      thione tautomeric form at the 6-position; (5) a pyridine-type nitrogen (= N-) or
      a methine group at the 7-position; (6) a methine group at the 8-position; (7) a
      pyrrole-type nitrogen or a carbon at the 9-position; and (8) no exocyclic
      substituents at the 9-position. These findings provide the basis for the rational
      design of additional ligands of hypoxanthine, guanine, and xanthine
      phosphoribosyltransferase activities in T. gondii.

PMID- 7503773
TI  - Induction in the gene RNR3 in Saccharomyces cerevisiae upon exposure to different
      agents related to carcinogenesis.
AB  - The induction of the gene RNR3 was investigated in yeast Saccharomyces cerevisiae
      using RNR31 lacZ fusion. Gene induction was monitored by measuring beta
      galactosidase activity. Various drugs that cause DNA damage effectively induced
      RNR3 expression; alkylating agents (cisplatin, mitomycin C and N-methyl-N'-nitro
      N-nitrosoguanidine), a radical producer (bleomycin), and an intercalator
      (actinomycin D) induced RNR3. When yeast expressing rat CYP1A1 was exposed to 2
      aminofluorene, a concentration-dependent induction of RNR3 was observed.
      Aflatoxin B1 also induced the expression of RNR3 in the same yeast strain
      concomitant with inhibition of cell growth. In control yeast, no induction of
      RNR3 was observed upon exposure to 2-aminofluorene or aflatoxin B1. Exposure to 2
      acetylaminofluorene or benzo[a]pyrene did not lead to induction of RNR3 in yeast
      expressing CYP1A1. These results indicate that DNA damage by chemicals related to
      carcinogenesis induces RNR3, and that activation of these procarcinogens was
      required for DNA damage-dependent induction of RNR3.

PMID- 7503774
TI  - Interaction of drugs with P-glycoprotein in brain capillaries.
AB  - P-glycoprotein (P-gp) is expressed at high levels in a variety of non-cancerous
      tissues such as the endothelial cells of the blood-brain barrier (BBB)
      capillaries. These thin capillaries tightly regulate the movement of substrates
      from the circulating blood into the brain. P-gp may be involved in the exclusion
      of various drugs from the capillary endothelial cells, blocking their entry into
      the brain. However, interactions of drugs with P-gp expressed in brain
      capillaries remain to be characterized. We have performed photoaffinity labeling
      studies using [125I]arylazidoprazosin (IAAP) to evaluate the inhibitory
      efficiency of various compounds. Cyclosporin A (CsA) and its derivative PSC 833
      (PSC) were the most effective inhibitors of IAAP binding among the drugs tested.
      The magnitude of inhibition was: PSC > CsA > quinidine > vinblastine > verapamil
      < actinomycin D > colchicine > reserpine > bilirubin > doxorubicin >
      progesterone. Cremophor El, the vehicle used to administer CsA and PSC
      intravenously, was also able to inhibit IAAP photolabeling of P-gp. Labeling
      experiments were also performed using a photoactivatable [3H]CsA derivative.
      Photolabeling of P-gp with this compound was abolished almost completely by CsA
      and PSC. In vivo studies were also performed by treating rats with CsA [10
      mg/(kg.day) for 10 days]. Following this treatment, no alteration in the level of
      P-gp expression in brain capillaries was observed. These results suggest that, at
      the proper dosage, administration of CsA to cancer patients could help to enhance
      the response of brain tumors to chemotherapeutic agents without modifying the
      intrinsic level of P-gp expression in this tissue.

PMID- 7503775
TI  - Biochemical characterization of ethanol actions on dihydropyridine-sensitive
      calcium channels in brain synaptosomes.
AB  - This study was undertaken to investigate the biochemical events underlying the
      inhibitory action of ethanol on dihydropyridine-sensitive voltage-dependent Ca2+
      channels in brain synaptosomes. The binding of radiolabeled dihydropyridine was
      used to determine functional Ca2+ channels in synaptosomes following exposure to
      ethanol. No effect on [3H]PN 200-110 binding was found when disrupted
      synaptosomal membranes were incubated with ethanol concentrations as high as 300
      mM, suggesting that ethanol did not interact directly with sites on or near the
      Ca2+ channels. However, when intact synaptosomes were first incubated with
      ethanol (100 mM) at 37 degrees and then disrupted, a significant reduction in
      membrane binding of [3H]PN 200-110 was found. Ethanol incubation of synaptosomes
      at 0 degree was ineffective. It appears that metabolic processes involving
      intracellular factors were required in the ethanol action. In examining this
      possibility, [3H]PN 200-110 binding was activated by incubation of disrupted
      membranes with MgATP and Ca(2+)-calmodulin, and ethanol was found to inhibit the
      activation in a concentration-dependent manner (50-200 mM). [3H]PN 200-110
      binding to membranes was also activated by incubation with MgATP and cyclic AMP
      dependent protein kinase, but this activation was not inhibited by ethanol. These
      findings are consistent with the interpretation that ethanol acts on Ca2+
      channels by inhibiting calmodulin-dependent activation of the channels.

PMID- 7503776
TI  - Up-regulation of glutathione synthesis in rat kidney by methyl mercury.
      Relationship to mercury-induced oxidative stress.
AB  - Prolonged exposure of rats to methyl mercury hydroxide (MMH) results, during the
      initial phase of exposure, in the rapid accumulation of mercury as Hg2+ by kidney
      cortex and in a significant increase in oxidative stress, as characterized by the
      rate of formation of thiobarbituric acid reactive substances (TBARS) by renal
      mitochondria. These events are accompanied by a progressive increase in steady
      state levels of the mRNA encoding gamma-glutamylcysteine synthetase (GCS), the
      rate-limiting enzyme in glutathione (GSH) synthesis and a 2- to 3-fold elevation
      in renal cortical GSH levels. The present study showed that the increase in GSH
      content was accompanied by a concomitant decrease in the rate of TBARS formation.
      Subsequent to these initial phase events, continued MMH exposure was
      characterized by equilibration in the rate of renal Hg2+ accumulation, a sharp
      decrease in both the TBARS formation rate and GCS mRNA level, but sustained
      elevation of renal cortical GSH content. Depletion of GSH with buthionine
      sulfoximine subsequent to the decline in the rate of TBARS formation did not
      result in a rebound of the TBARS formation rate. These findings suggest that
      oxidative stress during the initial phase of MMH exposure is derived from the
      transformation of CH3Hg+ to Hg2+, which, in turn, induces the synthesis of Hg(2+)
      and/or oxidant-scavenging GSH molecules via the up-regulation of renal GCS mRNA.
      The findings also suggest that resistance to Hg(2+)-mediated oxidative stress may
      be more closely associated with the capacity for up-regulation of GSH synthesis
      than with elevated GSH levels per se.

PMID- 7503777
TI  - Localisation of the multidrug resistance-associated protein, MRP, in resistant
      large-cell lung tumour cells.
AB  - The drug transport protein, P-glycoprotein, confers multidrug resistance (MDR) by
      expelling drugs across the cell surface. The structurally similar multidrug
      resistance-associated protein, or MRP, is also involved with drug efflux. In MDR
      variants of the human lung tumour cell line COR-L23 that overexpress MRP, there
      are also changes in intracellular drug distribution. To ascertain whether MRP
      could be involved in either process, experiments were performed to identify where
      MRP was located in these cells. Following separation of membranes by sucrose
      gradient centrifugation, MRP was found predominantly in the lighter membrane
      fractions containing plasma membrane enzyme activity. Immunofluorescent staining
      with a monoclonal antibody raised against MRP confirmed that MRP is present at
      the cell surface of these MDR lung tumour cells.

PMID- 7503778
TI  - 6-Isopropoxy-9-oxoxanthene-2-carboxylic acid (AH 6809), a human EP2 receptor
      antagonist.
AB  - On studying the interaction of various ligands with the pharmacologically
      defined, recombinant human EP2 receptor (Regan et al., Mol Pharmacol 46: 213-220,
      1994), we discovered that the putative EP1 receptor antagonist 6-isopropoxy-9
      oxoxanthene-2-carboxylic acid (AH 6809) also has affinity for the human EP2
      receptor. Moreover, AH 6809 behaved as an EP2 receptor antagonist and inhibited
      prostaglandin E2 (PGE2)-stimulated increases in cyclic AMP. These findings have
      significant implications for studies that employ AH 6809 to determine the
      pharmacological basis of PGE2-induced responses in human cells and tissues.

PMID- 7503779
TI  - Isoforms of nitric oxide synthase. Properties, cellular distribution and
      expressional control.

PMID- 7503780
TI  - Reduction of dihydroxyphenylacetic acid by a novel enzyme in the rat brain.
AB  - A novel enzyme that converts dihydroxyphenylacetic acid (DOPAC) to
      dihydroxyphenylethanol (DOPET) was found to be present in the microdialysate of
      the rat brain. The enzyme, named DOPAC reductase, was inhibited by EDTA and
      stimulated by divalent cations like Zn2+, Mn2+, Co2+ and Cu2+. Its Km, pH optimum
      and temperature optimum were found to be 32 +/- 2 microM, 7.5 and 40 degrees,
      respectively. The equivalent acid metabolite of noradrenaline, 3,4
      dihydroxymandelic acid, and the methoxylated acids of both noradrenaline and
      dopamine, 3-methoxy-4-hydroxymandelic acid and 3-methoxy-4-hydroxyphenylacetic
      acid, were found not to be substrates of DOPAC reductase. Thus, DOPAC reductase
      may be an enzyme that is specifically involved in the one-step conversion of
      DOPAC to DOPET in the central metabolism of dopamine.

PMID- 7503781
TI  - The uptake of ascorbic acid into human umbilical vein endothelial cells and its
      effect on oxidant insult.
AB  - Intracellular reduced ascorbate (AA) levels in confluent cultures of human
      umbilical vein endothelial (HUVE) cells, grown under conventional conditions,
      were shown to be very low, ranging between undetectable, < 0.1 nmol/mg protein,
      and 0.3 nmol/mg protein. Reduced ascorbate was accumulated into the endothelial
      cells from M199 culture medium in time- and concentration-dependent manners, and
      was saturated at medium concentrations related to the normal plasma
      concentrations of the antioxidant (i.e. between 50 microM and 100 microM). Cells
      derived from different individuals demonstrated considerable inter-individual
      variation in these AA uptake parameters. The uptake of AA was sensitive to
      temperature and the presence of the structural analogue isoascorbate in the
      medium, indicating the involvement of an active transport mechanism. A role for
      the glucose transporter is, however, not indicated, as AA uptake was not
      sensitive to phloretin, an inhibitor of the cellular glucose transporter, nor
      greatly enhanced by depletion of glucose from the medium. Incubation of HUVE
      cells with dehydroascorbate (DHAA) caused a dose-dependent, but transient
      increase in intracellular AA. This indicates that HUVE cells are both competent
      in the uptake and intracellular reduction of oxidised ascorbate, and may
      resecrete AA into the medium. Indeed, reduced ascorbate in the medium was shown
      to be preferentially maintained in the presence of cells. The uptake of AA was
      not sensitive to the presence of DHAA in the medium, perhaps indicating different
      transporters for reduced and oxidised forms of ascorbate in these human cells.
      Pre-loading HUVE cells with AA was shown to protect control cells only weakly
      from the acute, sub-lethal toxicity of H2O2 generated by xanthine oxidase (1 U/mL
      or 10 U/mL). Protection was optimal at intracellular levels of 3-4 nmol AA/mg
      protein, with higher concentrations lacking a protective effect. Additionally,
      the presence of the iron chelator, desferoxamine, significantly protected GSH
      depleted HUVE cells only in response to the peroxide, but did not potentiate the
      protective action of intracellular AA in either control or GSH-depleted cells.
      This indicates that ascorbate-driven redox-cycling of the Fe2+/Fe3+ does not
      hamper the intracellular protective function of ascorbate during hydrogen
      peroxide-derived oxidative stress. These results are discussed in terms of the
      central role of endothelial cells in the distribution of AA to the tissues of the
      body, the use of the HUVE cell system for model studies of the toxicity of
      oxidants in the human endothelium, and the balance between the antioxidant and
      pro-oxidant actions of AA.

PMID- 7503782
TI  - Antitumour effects of pure diastereoisomers of 5-formyltetrahydrofolate in
      hepatic transplants of a rodent colon carcinoma model.
AB  - The effects of the two diastereoisomers of 5-formyltetrahydrofolate on tumour
      growth, thymidylate synthase (TS, EC 2.1.1.45) levels, and potentiation of 5
      fluorouracil cytotoxicity were studied in an in vivo rat colon carcinoma model,
      transplanted to liver. The animals were randomized into eight groups, treated
      with daily i.v. tail vein injections of racemic (d,l)-5-formyltetrahydrofolate (5
      CHO-FH4), 15 mg/kg, (1)-5-CHO-FH4 7.5 mg/kg, and (d)-5-CHO-FH4 7.5 mg/kg, 5
      fluorouracil (FUra) 30 mg/kg, (d,l)-5-CHO-FH4 15 mg/kg+FUra 30 mg/kg, (l) 5-CHO
      FH4 7.5 mg/kg+FUra 30 mg/kg, and (d)-5-CHO-FH4 7.5 mg/kg+FUra 30 mg/kg, and a
      sham-treated control group. The average tumour size of the groups was equal at
      the start of treatment. After six days' treatment the average tumour sizes were
      at laparotomy 3.3 +/- 1.0 g in the (d/l)-5-CHO-FH4 treated group, compared to 2.0
      +/- 0.1 g in the FUra treated group and 7.1 +/- 3.1 g in the controls. Natural
      (l)-5-CHO-FH4 promoted tumour growth (average tumour weight 10.8 +/- 4.0 g),
      whereas the unnatural (d)-5-CHO-FH4 alone retarded it (average tumour weight 1.2
      +/- 0.40 g). (l)-5-CHO-FH4 induced a significant increase in tumour tissue TS
      levels by [3H]FdUMP radioligand assay (27.5 +/- 8.4 pmol/g tumour tissue)
      compared to controls (16.8 +/- 6.1 pmol/g tumour tissue). Increases in 5,10
      methylenetetrahydrofolate and tetrahydrofolate occurred with FUra alone, with a
      further statistically significant increase in both folates with the addition of
      (d)-5-CHO-FH4 to FUra.

PMID- 7503783
TI  - Genetic analysis of microsomal epoxide hydrolase in patients with carbamazepine
      hypersensitivity.
AB  - Carbamazepine therapy is occasionally complicated by hypersensitivity reactions,
      the mechanism of which is poorly understood. It has been suggested that affected
      individuals may have a genetically-determined defect of microsomal epoxide
      hydrolase. The aim of this study was to determine whether a single genetic
      mutation or pattern of mutations could be used to predict individual
      susceptibility to carbamazepine-hypersensitivity. DNA was isolated from 10
      carbamazepine-hypersensitive patients and 10 healthy volunteers. The patients had
      developed various forms of toxicity with carbamazepine, including toxic epidermal
      necrolysis, Stevens-Johnson syndrome, hepatitis and pneumonitis. The technique of
      polymerase chain reaction single-strand conformation polymorphism analysis (PCR
      SSCP) was used to screen for mutations in all nine exons of the microsomal
      epoxide hydrolase gene. Any new mutations detected by this method were
      characterised by direct sequencing of the DNA. In addition, in the most severely
      affected patient, we sequenced all nine exons of the gene. There was a higher
      frequency of mutations in the hypersensitive group when compared with the
      controls, but there was no consistent mutation (or pattern of mutations) in the
      microsomal epoxide hydrolase gene which was common to the hypersensitive group.
      DNA sequencing of all nine exons of the microsomal epoxide hydrolase gene from
      the most severely affected patient showed the sequence to be "wild-type," when
      compared to the previously published sequences. The results of this study suggest
      that a single mutation within the coding region of the microsomal epoxide
      hydrolase gene cannot be the sole determinant of the predisposition to
      carbamazepine hypersensitivity.

PMID- 7503784
TI  - Kinetic parameters of lymphocyte microsomal epoxide hydrolase in carbamazepine
      hypersensitive patients. Assessment by radiometric HPLC.
AB  - Idiosyncratic hypersensitivity reactions with carbamazepine have been postulated
      to be due to a deficiency of microsomal epoxide hydrolase (HYL1), although this
      is based on indirect evidence. Using 3H-cis stilbene oxide (0.5 Ci/mmol) as a
      substrate, we have developed a radiometric HPLC assay sensitive enough to measure
      the kinetic parameters of HYL1 in lymphocytes. The intra-assay coefficient of
      variation was 8%. Enzyme activity has been measured in lymphocytes from six
      carbamazepine hypersensitive patients, six patients on carbamazepine without any
      adverse effects, and twelve drug-naive healthy volunteers. No significant
      difference was observed in three kinetic parameters of the enzyme among these
      three groups. The values for Km, Vmax, and intrinsic clearance ranged from 6.1
      89.9 microM, 3.0-23.2 pmoles diol formed/min/mg protein, and 0.147-0.493
      microliter/min/mg protein. There was no difference in enzyme activity between
      patients currently on carbamazepine and healthy volunteers, indicating a lack of
      induction of lymphocyte HYL1 by carbamazepine. Co-incubation of lymphocytes with
      1,1,1-trichloropropene oxide, an inhibitor of hepatic HYL1, resulted in an 82%
      inhibition of activity, similar to that observed with the hepatic enzyme. The
      healthy volunteers were genotyped as being either GSTM1 positive (n = 6) or GSTM1
      negative (n = 6). This did not affect the kinetic parameters of lymphocyte
      microsomal epoxide hydrolase. Our results suggest that there is normal HYL1
      activity in lymphocytes of hypersensitive patients using cis-stilbene oxide as a
      substrate.

PMID- 7503785
TI  - The interaction of nitroaromatic drugs with aminothiols.
AB  - The effect of cysteamine and glutathione addition on the redox behaviour of
      metronidazole, chloramphenicol, M&B 4998, nitrofurazone, and nifuroxime has been
      studied by electrochemical techniques. The presence of thiol influences the redox
      behaviour of the nitro compound in a number of ways. In aqueous media, the single
      step nitro/hydroxylamine reduction shows a decrease in current and a shift to
      more positive potentials, which is assigned to the thiol acting as the reducing
      agent, but only after the formation of the nitro radical anion. In addition, the
      reversible RNO/RNHOH couple is greatly diminished or removed. In a
      dimethylformamide/H2O solvent, the nitro radical anion can be selectively
      generated. The effect of thiol addition on the stability of the radical anion is
      strongly dependent on the drug, the identity of the thiol, and the concentration
      of the supporting electrolyte. The presence of thiol can result in an increase or
      a decrease in the lifetime of the radical with no apparent correlation with the
      redox couple of the nitro compound, or can act as an oxidizing agent and
      regenerate the original nitro compound. These disparate routes by which thiol can
      modify the redox characteristics of nitro compounds suggest that the traditional
      role of thiol as a radical scavenger needs to be extended.

PMID- 7503786
TI  - Spermidine attenuation of volatile anesthetic inhibition of glutamate-stimulated
      [3H](5D,10S)-(+)-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine
      ([3H]MK-801) binding to N-methyl-D-aspartate (NMDA) receptors in rat brain.
AB  - The influence of spermidine, a polyamine agonist, on volatile anesthetic
      inhibition of N-methyl-D-aspartate (NMDA) receptor activation, as indicated by
      glutamate stimulation of [3H]MK-801 ([3H](5D,10S)-(+)-methyl-10,11-dihydro-5H-
      dibenzo[a,d]cyclohepten-5,10-imine) binding, was studied in rat brain. Spermidine
      reserved the inhibition caused by four volatile anesthetics (enflurane,
      halothane, methoxyflurane and chloroform) at the same concentrations (EC50
      approximately 3 microM) at which it potentiated glutamate opening of the NMDA ion
      channel. The anesthetics had no effect on the direct stimulation of channel
      opening by spermidine, which occurred at concentrations of spermidine greater
      than 30 microM in the absence of receptor agonist. In these actions, spermidine
      closely resembled the allosteric co-agonist glycine. The present results suggest
      that anesthetic action on NMDA receptors involves a set of sites on the channel
      complex that is distinct from the recognition sites for glutamate, glycine, and
      channel blockers, and are consistent with the idea that blockade of NMDA
      receptors contributes to the development of the anesthetic state.

PMID- 7503787
TI  - The influence of 2-chloro-2'-deoxyadenosine on metabolism of deoxyadenosine in
      human primary CNS lymphoma.
AB  - The effects of 2-chloro-2'-deoxyadenosine (2CdA) on the activity of enzymes
      important for the metabolism of deoxyadenosine were studied in lysates prepared
      from human primary central nervous system (CNS) lymphomas and normal human
      lymphocytes. Strong inhibition (approximately 100%) of the phosphorylation of
      deoxyadenosine to its deoxynucleotide phosphate derivatives was produced in both
      systems in the presence of 2CdA, which was phosphorylated concomitantly to 2
      chloro-2'-deoxyAMP. Interestingly, 2CdA was also found to be an inhibitor of the
      deamination of both deoxyadenosine (over 50%) and AMP (70%). These findings add
      to our understanding of the mechanisms of toxicity of this drug, especially
      considering that 2CdA is resistant to deamination by adenosine deaminase. These
      results challenge the existing theories of 2CdA toxicity, which have been limited
      to the formation of phosphate derivatives of 2CdA. The present in vitro studies
      have demonstrated that 2CdA also inhibits both phosphorylation and deamination of
      deoxyadenosine (dAdo), suggesting that its mechanism of toxicity includes a block
      in dAdo metabolic pathways. This has important implications for the perturbation
      of cell methylation, a functionality associated with, for example, apoptosis.

PMID- 7503789
TI  - Studies on urea synthesis in the liver of rats treated chronically with ethanol
      using perfused livers, isolated hepatocytes, and mitochondria.
AB  - Changes in urea synthesis in the liver of rats treated with 32% ethanol in the
      drinking water for up to 6 months were studied using perfused livers, isolated
      hepatocytes, and mitochondria. Results obtained from ethanol-treated rats are
      summarized as follows: (1) the mitochondria of the hepatocytes of rats treated
      with ethanol for 2 months or longer became enlarged to various degrees, (2) the
      levels of ammonia in the serum remained within a normal range, while those in
      liver tissue were elevated compared with the control, (3) urea synthesis from
      ammonia in perfused livers was decreased markedly, while that from citrulline
      remained in the normal range, (4) the activities of carbamyl phosphate synthetase
      (CPS; EC 2.7.2.5) and ornithine transcarbamylase (OTC; EC 2.1.3.3) in
      mitochondria were unchanged compared with those of the control, and (5) the
      levels of ATP in liver tissue and the ability of mitochondria to synthesize ATP
      were decreased markedly compared with the control. Both the level of ATP in the
      hepatocytes and the synthesis of urea from ammonia by perfused livers of rats
      treated with ethanol were resistant to externally added ethanol, while those of
      control animals were severely affected. These results suggest that the
      intracellular level of ATP is intimately related to urea synthesis in both
      control and ethanol-treated animals, and lowered levels of ATP may be a key
      factor in the suppression of urea synthesis in ethanol-treated animals.

PMID- 7503788
TI  - Human liver oxidative metabolism of O6-benzylguanine.
AB  - The oxidation of O6-benzylguanine, an inactivator of O6-alkylguanine-DNA
      alkyltransferase, was examined using human liver cytosol, microsomes, and several
      P450 isoforms. Incubation of O6-benzylguanine with human liver cytosol resulted
      in the formation of O6-benzyl-8-oxoguanine, which was inhibited by menadione, a
      potent inhibitor of aldehyde oxidase. Inhibition by allopurinol, a xanthine
      oxidase inhibitor, was less dramatic. Oxidation of O6-benzylguanine also occurred
      with pooled human liver microsomes and was inhibited by both furafylline and
      troleandomycin, selective inhibitors of CYP1A2 and CYP3A4, respectively. Human
      P450s CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2E1, and CYP3A4 expressed in Hep G2
      hepatoma cells using vaccinia virus vectors were incubated with 10 or 200 microM
      O6-benzylguanine. At 10 microM, O6-benzylguanine was oxidized primarily by CYP1A2
      and to a lesser extent by CYP3A4. However, an appreciable increase in CYP3A4
      contribution was noted at 200 microM. CYP1A2 exhibited a more than 200-fold
      higher relative catalytic activity (Vmax/Km) compared with CYP3A4. Therefore, at
      therapeutically relevant concentrations of O6-benzylguanine, CYP1A2 could be
      primarily involved in its oxidation since it shows a much lower Km value (1.3
      microM) than CYP3A4 (52.2 microM) and cytosol (81.5 microM). However, one would
      expect interindividual variation in the extent of oxidation of O6-benzylguanine
      depending on the levels of aldehyde oxidase, CYP1A2, and CYP3A4.

PMID- 7503790
TI  - beta-Naphthoflavone-inducible cytochrome P4501A1 activity in liver microsomes of
      the marine safi fish (Siganus canaliculatus).
AB  - The cytochrome P450-dependent metabolism of benzo(a)pyrene and other xenobiotics
      has been investigated in liver microsomes prepared from a local marine safi fish,
      Siganus canaliculatus. The safi fish was found to have a well-developed
      microsomal monooxygenase system consisting of cytochrome P450, cytochrome b5 and
      NADPH-cytochrome c reductase. The fish microsomal enzyme system was able to
      metabolize benzo(a)pyrene, 7-ethoxycoumarin and 7-ethoxyresorufin. Male fish were
      found to exhibit a higher monooxygenase activity than female fish. Treatment of
      fish with beta-naphthoflavone was found to induce (2- to 4-fold) the activities
      of aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase and ethoxyresorufin
      O-deethylase. HPLC analysis of the metabolites produced by incubation of
      benzo(a)pyrene with the liver microsomal preparation showed a predominant
      formation of 3-OH and 9-OH benzo(a)pyrene. There was an increased formation of
      benzo(a)pyrene 7,8-diol and benzo(a)pyrene 7,8,9,10-tetrol in liver microsomes
      prepared from beta-naphthoflavone-treated fish. Western immunoblot analysis of
      liver microsomes from beta-naphthoflavone-treated fish using an antibody to rat
      liver cytochrome P4501A1 (CYP1A1) suggested the presence of an inducible
      cytochrome P450 enzyme that was comparable with that of rat liver enzyme. Our
      results suggest that liver microsomes from the safi fish have multiple forms of
      cytochrome P450 with a specific beta-naphthoflavone-inducible CYP1A1 homologous
      protein that can metabolize a variety of substrates.

PMID- 7503791
TI  - Induction of cytochrome P450-dependent monooxygenase in serum-free cultured Hep
      G2 cells.
AB  - We examined the induction of cytochrome P450-dependent mixed-function
      monooxygenase (MFO) in the human hepatoma cell line Hep G2 by means of several
      factors. The MFO activities induced in the cells cultured in medium containing
      five commercial sera varied significantly, and the activity in the cells cultured
      in the absence of serum was about twice as high as that in cells supplemented
      with serum. The activity of ethoxycoumarin O-deethylase was highest 12 hr after
      adding 3-methylcholanthrene, and it was induced by several polycyclic aromatic
      hydrocarbons such as benzo(a)anthracene and benzo(a)pyrene, which are usually
      found in urban air as environmental contaminants. Furthermore, an extract from
      the total suspended particles collected using a high volume air sampler, which
      was mutagenic in the Ames assay using Salmonella typhimurium TA98, induced the
      same enzyme activities in Hep G2 cells. These findings suggest that serum-free
      culture allows the stable and highly sensitive measurement of induced MFO
      activity, and that studies of MFO induction by environmental samples using human
      hepatoma Hep G2 cells should provide helpful information regarding the risk
      associated with environmental contaminants.

PMID- 7503792
TI  - HPLC and 31P NMR characterization of the reaction between antitumor platinum
      agents and the phosphorothioate chemoprotective agent S-2-(3
      aminopropylamino)ethylphosphorothioic acid (WR-2721).
AB  - In prior studies, we examined the effects of the radioprotective and
      chemoprotective agent WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid]
      on the in vivo biotransformation of the cisplatin [cis
      diamminedichloroplatinum(II)] analog ormaplatin [(d,I)trans-1,2
      diaminocyclohexanetetrachloroplatinum(IV), Pt(dach)Cl4, (formerly called
      tetraplatin)]. Those data suggested that a direct interaction between WR-2721 and
      ormaplatin and/or the corresponding Pt(II) drug, Pt(dach)Cl2, may be occurring in
      vivo. This would be in contrast to the generally accepted hypothesis that WR-2721
      is a prodrug that must first be converted by alkaline phosphatase to a free thiol
      compound, WR-1065, before any appreciable reactivity would be evident. However,
      the major biotransformation product observed in the peritoneal fluid, plasma, and
      all tissues was Pt(dach)(WR-1065). We report here on further investigations into
      the in vitro reactivity of Pt(dach) compounds with WR-2721 and WR-1065.
      Separation of reaction products resulting from incubation of Pt(dach)(malonato)
      with either WR-2721 or WR-1065 under physiological conditions gave profiles that
      were indistinguishable by reverse phase HPLC and cation exchange HPLC at two
      different pHs. 31P NMR characterization of the dephosphorylation of WR-2721
      revealed essentially no loss of inorganic phosphate for up to 24 hr when
      incubated in unbuffered water at 30 degrees. In contrast, when incubated with a
      1:1 molar ratio of cisplatin under the same conditions, the WR-2721 signal was
      decreased markedly in the first 5 min, and had disappeared almost completely by 1
      hr. The signal corresponding to inorganic phosphate increased in parallel to the
      decrease in the WR-2721 signal. No intermediate formation of a complex containing
      both platinum and phosphate could be detected at any time. These data suggest
      that the reaction between WR-2721 and platinum complexes results in rapid
      dephosphorylation of WR-2721, and, consequently, that the reaction products
      formed with either WR-2721 or WR-1065 and Pt(II) complexes are identical.

PMID- 7503793
TI  - Reduction of intracellular pH by tenidap. Involvement of cellular anion
      transporters in the pH change.
AB  - Tenidap [5-chloro-2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-oxo-1H- indole-1
      carboxamide], a novel antirheumatic agent, produces a rapid and sustained
      intracellular acidification when applied to cells in culture. To investigate the
      mechanism by which this change in ionic homeostasis is achieved, the
      acidification activities of structural analogs of tenidap were determined, and
      the movements of [14C]tenidap into and out of cells were explored. The
      acidification activity of tenidap was enhanced by lowering extracellular pH,
      suggesting that the free acid species was required for this process. Consistent
      with this requirement, a non-acidic analog of tenidap did not produce a change in
      intracellular pH (pHi). In contrast, multihalogenated derivatives of tenidap
      produced greater changes in pHi than did tenidap, and one analog produced a
      transient acidification from which the cell recovered; this recovery, however,
      was blocked by an inhibitor of the Na+/H+ antiporter. Fibroblasts incubated with
      [14C]tenidap achieved within 5 min a level of cell-associated drug that remained
      constant during longer incubations. Simultaneous addition of the electrogenic
      ionophore valinomycin or the P-glycoprotein inhibitor 4-(3,4-dihydro-6,7
      dimethoxy-2(1H)-isoquinolinyl)-N-[2-(3,4-dimethoxyphe nyl) ethyl]-6,7-dimethoxy-2
      quinazolinamine (CP-100,356) caused a time- and concentration-dependent increase
      in the level of cell-associated [14C]tenidap; other agents tested did not promote
      this enhanced cellular accumulation. [14C]Tenidap accumulated by fibroblasts in
      the presence of CP-100,356 subsequently was released when these cells were placed
      in a tenidap- and CP-100,356-free medium. Importantly, several agents that are
      known to inhibit anion transport processes, including alpha-cyano-beta-(1
      phenylindol-3-yl) acrylate, 5-nitro-2(3-phenylpropylamino)-benzoic acid, and
      meclofenamic acid, inhibited efflux of [14C]tenidap. In contrast, ethacrynic acid
      and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid did not impair the efflux
      process. Likewise, tenidap analogs that produced a sustained intracellular
      acidification blocked the efflux of [14C]tenidap, but non-acidifying species did
      not. These data suggest that movements of tenidap into and/or out of cells is a
      facilitated process subject to pharmacological intervention. Together, the
      structural selectivity of the acidification response and the evidence of
      facilitated transport suggest that the pHi modulating activity of tenidap is
      dependent on its unique physicochemical properties. Due to the dependence of
      these physicochemical properties on environmental and cellular conditions, in
      vivo expression of the acidification activity is likely to occur only within
      restricted environments that favor this tenidap-induced process.

PMID- 7503794
TI  - Use of 4-fluoro-L-ornithine to monitor metabolic flux through the polyamine
      biosynthetic pathway.
AB  - The mechanistic effectiveness of various polyamine analogs and enzyme inhibitors
      is typically determined by their ability to deplete intracellular polyamine
      pools. In this study, we describe an assay that may prove useful in augmenting
      this relatively static assessment of drug action. The assay relies upon the
      substitution of 4-fluoro-L-ornithine (Fl-Orn) for ornithine as a polyamine
      precursor to provide a means to measure metabolic flux through polyamine pools.
      At concentrations up to 500 microM, the analog did not inhibit the growth of
      L1210 murine leukemia cells during incubations of up to 72 hr. Using HPLC, the
      analog was processed metabolically over time to what was deduced to be 2
      fluoroputrescine, 6-fluorospermidine and 6-fluorospermine. The relative
      proportion of fluorinated polyamine analog to the natural polyamine increased
      with time and Fl-Orn concentration. The sum of the two was found to be nearly
      identical to the respective polyamine pool of control cells exposed instead to
      500 microM ornithine. This indicates that Fl-Orn was recognized and utilized as a
      precursor at a rate very similar to that of ornithine itself. Using L1210 cells
      at different stages of cell growth, it was determined that the metabolic flux
      through the pools, as indicated by the rate of appearance of individual
      fluorinated polyamine species, reflected the proliferation status of the cells-
      non-growing cells failed to incorporate the analog. Likewise, in cell types with
      varying polyamine pool profiles, such as polyamine enzyme overproducers or those
      with constitutively different spermidine of spermine ratios, the incorporation of
      the fluorinated analogs into pools was found to be proportional to the size to
      the natural polyamine pool. In cells treated with inhibitors of S
      adenosylmethionine decarboxylase, Fl-Orn incorporation indicated a total blockade
      of polyamine synthesis at that enzyme site. Overall, the Fl-Orn assay has
      demonstrated that polyamine pool profiles generally reflect the rate of flux
      through the pathway in proliferating cells, suggesting that most intracellular
      polyamines are freely exchangeable with those undergoing metabolic flux.

PMID- 7503795
TI  - Sensitive method for quantitation of angiotensin-converting enzyme (ACE) activity
      in tissue.
AB  - A novel sensitive and specific method for the measurement of tissue angiotensin
      converting enzyme (ACE) activity utilizing HPLC is described. ACE activity was
      determined in detergent-extracted canine hearts utilizing the synthetic ACE
      specific substrate hippuryl histidyl leucine (HHL), both in the presence and the
      absence of the site-specific inhibitor captopril. Tissue ACE activity was
      quantitated from the moles of hippuric acid (HA) formed, in time-fixed assays,
      utilizing HPLC separation of HA from HHL and UV-spectrophotometry for
      quantitation of HA as in the standard Cushman and Cheung assay (Cushman DW and
      Cheung HS, Biochem Pharmacol 20: 1637-1648, 1971). Separation of HA from HHL was
      performed by reverse phase HPLC on a phenyl silica gel column with an eluent
      consisting of 20% acetonitrile in 0.1 M aqueous ammonium phosphate buffer, pH
      6.8. After the standard liquid/liquid extraction procedure with ethyl acetate,
      HPLC analysis revealed the presence of unreacted substrate, HHL, in amounts
      comparable to the product of interest, HA, in the final assay; moreover, the
      amount of HA formed did not fall completely to zero in the presence of captopril.
      Regional studies of canine cardiac ACE activity utilizing the HPLC-based assay
      and the standard assay method showed a significantly higher ACE activity in the
      right ventricle compared with the left ventricle (2.37 +/- 0.7 vs 1.24 +/- 0.18
      mU/g, P < 0.05 [N = 6], respectively) in the HPLC-based assay, but no difference
      in right and left ventricular ACE activities by the standard assay (0.25 +/- 0.08
      vs 0.31 +/- 0.09 mU/g [N = 6], respectively). Kinetic studies utilizing the HPLC
      based assay coupled with the use of captopril showed Km (1.34 +/- 0.08 mM) and
      Vmax (36.8 +/- 11.5 x 10(-10) M/min) values in agreement with those in the
      literature. Our results demonstrate that the application of HPLC to the standard
      Cushman and Cheung assay improves the sensitivity and specificity of the standard
      assay and enables the use of much smaller amounts (approximately 4 vs
      approximately 400 mg for the Cushman and Cheung assay) of tissue for ACE activity
      assay.

PMID- 7503796
TI  - Metabolism of angiotensin I in isolated rat hearts. Effect of angiotensin
      converting enzyme inhibitors.
AB  - In this study, the formation of biologically active angiotensins from angiotensin
      I (Ang I) in isolated rat hearts was evaluated. The role of angiotensin
      converting enzyme (ACE) in Ang I metabolism was also investigated. HPLC analysis
      of heart perfusate showed that 125I-Ang I was metabolized extensively (single
      passage) in the rat coronary circulation in vitro leading to the formation of the
      biologically active angiotensins: angiotensin II (Ang II), Ang-(2-8), Ang-(3-8)
      and Ang-(1-7). Ang II was the major product identified in HPLC fractions,
      corresponding to 7.8 +/- 0.89% of the total radioactivity recovered. A similar
      profile was observed when single-passage metabolism of non-isotopic Ang I was
      evaluated by HPLC, followed by radioimmunoassay of the eluate fractions. When
      125I-Ang I was perfused in the presence of ACE inhibitors (enalaprilat,
      ramiprilat) in concentrations up to 130 microM, the formation of Ang II was only
      partially inhibited (approximately 50%). A similar tendency was observed for Ang
      (2-8), Ang-(3-8) and Ang-(2-7). The formation of Ang-(1-7) and its related
      fragments Ang-(3-7) and Ang-(4-7) was not changed significantly by ACE
      inhibitors, although a slight increase in formation of these fragments was
      observed. No significant changes were observed for the carboxyl-terminal
      fragments of Ang I: Ang-(2-10), Ang-(3-10), and Ang-(4-10). The fractional
      metabolism of Ang I was not modified by ACE inhibition. These findings suggest
      that biologically active angiotensins can be formed from Ang I in the rat
      coronary circulation. These locally generated peptides may contribute to the
      actions of the renin-angiotensin system in the heart.

PMID- 7503797
TI  - Proton release from HeLa cells and alkalization of cytoplasm induced by diferric
      transferrin or ferricyanide and its inhibition by the diarylsulfonylurea
      antitumor drug N-(4-methylphenylsulfonyl)-N'-(4-cholorophenyl) urea (LY181984).
AB  - Proton release from HeLa cells was stimulated by an external oxidant, potassium
      ferricyanide, or by the growth factor diferric transferrin. This stimulated
      proton release was inhibited by the antitumor sulfonylurea LY181984 [N-(4
      methylphenylsulfonyl)-N'-(4-chlorophenyl)urea] over the concentration range 10 nM
      to 1 microM. The antitumor-inactive sulfonylurea analog LY181985 [N-(4
      methylphenylsulfonyl)-N'-(phenyl)urea] was without effect at 1 microM and
      required 10-100 microM concentrations to inhibit proton release. Diferric
      transferrin-induced alkalization of the cytoplasm estimated by BCECF [2',7'-bis(2
      carboxyethyl)-5,(and 6)-carboxyfluorescein] fluorescence also was inhibited by 1
      microM LY181984 but not by 1 microM LY181985. The inhibited component appeared to
      be amiloride resistant. The proton release induced by either ferricyanide or
      diferric transferrin was inhibited by about 35% at a near optimal amiloride
      concentration of 0.2 mM or at a dimethylamiloride concentration of 0.075 mM.
      However, the induced proton release was inhibited further by LY181984.
      Conversely, when proton release was inhibited fully by LY181984 at a near optimal
      concentration of 10 microM (50% inhibition), increasing concentrations of
      amiloride or dimethylamiloride resulted in additional inhibitions of 16 and 23%,
      respectively. However, the inhibitions by LY181984 and the amilorides were
      additive, suggesting that amiloride and the sulfonylureas may act independently.
      Evidence for an action of the sulfonylurea in inhibiting proton efflux
      differently from that of the amilorides came from measurements of sodium uptake
      either by fluorometry or by direct measurement with 22Na+. Sodium uptake was not
      inhibited by either LY181984 or LY181985 in HeLa cells at concentrations of
      LY181984 sufficient to inhibit proton efflux by 80% or more. The results show
      LY181984 to be a potent inhibitor of diferric transferrin- or ferricyanide
      induced proton efflux and cytoplasmic alkalization in HeLa cells and that the
      inhibition may involve a component of proton transport that is resistant to
      amiloride.

PMID- 7503798
TI  - Naphthylisothiocyanate disposition in bile and its relationship to liver
      glutathione and toxicity.
AB  - 1-Naphthylisothiocyanate (ANIT), but not 2-naphthylisothiocyanate (BNIT),
      produces cholangiolitic hepatitis in rats after a single, oral administration.
      The mechanisms responsible for the disparate toxic outcomes for these closely
      related structural isomers are not fully understood. Recent reports suggest that
      ANIT-induced hepatotoxicity is dependent upon the formation and biliary excretion
      of a reversible glutathione-ANIT conjugate. To understand better the relationship
      between hepatic glutathione, secretion into bile and hepatotoxicity, the bile
      concentrations and hepatotoxicities of ANIT and BNIT were examined in rats with
      and without pretreatment with buthionine sulfoximine (BSO). ANIT (100 mg/kg,
      p.o.) caused a 3-fold elevation of plasma alanine aminotransferase activity
      (ALT), a 6-fold elevation of total plasma bilirubin, and a > 90% reduction in
      bile flow 24 hr after administration. BNIT, at this same dose and route of
      administration, did not alter significantly these markers of liver injury.
      Accumulation of ANIT and BNIT in bile occurred with the same temporal
      characteristics; however, BNIT accumulated to markedly larger concentrations (292
      +/- 83 and 235 +/- 100 microM BNIT and 78 +/- 19 and 29 +/- 13 microM ANIT at 1
      and 4 hr, respectively). The accumulation of ANIT and BNIT in bile was coincident
      with a > 2-fold elevation of reduced glutathione in bile. Pretreatment of rats
      with BSO decreased hepatic glutathione concentration and reduced the
      concentration of naphthylisothiocyanates in bile by 85%. Associated with this
      reduction was an attenuation of ANIT hepatotoxicity. Altogether, these findings
      indicate that both ANIT and BNIT accumulate in bile in a glutathione-dependent
      manner, yet they yield different hepatotoxic outcomes. Therefore, the disparity
      in hepatotoxicities observed with these isomers is not related to a difference in
      ability to enter bile. Other differences, such as in metabolism, chemical
      reactivity, conjugate stability and/or cytotoxic potential to bile duct
      epithelial cells may be more important determinants of hepatotoxicity.

PMID- 7503799
TI  - Enzymatic elimination of fluoride from alpha-fluoro-beta-alanine.
AB  - Rat liver homogenates catalyzed the elimination of fluoride from (R,S)-alpha
      fluoro-beta-alanine. The substrate specificity and physical properties of the
      defluorinating enzyme were similar to those of mitochondrial L-alanine-glyoxylate
      aminotransferase II (EC 2.6.1.44, AlaAT-II). Furthermore, AlaAT-II activity,
      measured with L-alanine and glyoxylate as substrates, copurified with the alpha
      fluoro-beta-alanine-defluorinating enzyme. The NH2-terminal sequence (18
      residues) of the enzyme did not show significant sequence similarity with any of
      the proteins currently listed in GenBank. The purified enzyme catalyzed the
      transamination of L-alanine (Ala) and glyoxylate (glyx) at pH 8.5 by a ping-pong
      mechanism with kinetic parameters of kcat = 17 sec-1, KL-Ala = 3.2 mM, and Kglyx
      = 0.3 mM, respectively. The kinetic parameters for the defluorination of (R)
      alpha-fluoro-beta-alanine and (S)-alpha-fluoro-beta-alanine were kcat = 6.2 and
      2.6 min-1, respectively, and Km = 2.7 and 0.88 mM, respectively. L-Alanine
      potently inhibited the defluorination reaction with an apparent Ki of 0.024 mM.
      (R,S)-alpha-Fluoro-beta-alanine converted the optical spectrum of the enzyme
      bound cofactor from the pyridoxal form to the pyridoxamino form, which indicated
      that this cofactor may participate in the defluorination reaction. The product of
      the enzymatic reaction, malonic semialdehyde, reacted nonenzymatically with (R,S)
      alpha-fluoro-beta-alanine to form an adduct that was detected spectrally. AlaAT
      II was not inactivated during dehalogenation of (R,S)-alpha-fluoro-beta-alanine
      but was inactivated completely during dehalogenation of beta-chloro-L-alanine.

PMID- 7503801
TI  - Comparative assessment of metabolic enzyme levels in macrophage populations of
      the F344 rat.
AB  - The immune system is a direct target for toxic insult by a number of drugs and
      other chemicals, many of which require activation to toxic metabolites by drug
      metabolizing enzymes. We compared the induction of drug-metabolizing enzymes,
      including cytochrome P450 1A1 (CYP1A1) and aldehyde dehydrogenase (ALDH), which
      are differentially expressed in various macrophage populations following
      treatment of F344 rats with the inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD). Kupffer cells, alveolar macrophages and splenic macrophages from TCDD
      treated animals expressed elevated levels of inducible CYP1A1 as compared to
      other macrophage subpopulations or cells from control rats. TCDD treatment also
      resulted in increased ethoxyresorufin-O-deethylase (EROD) activity and total
      cytochrome P450 content in tissue-derived macrophages. Immunoreactive protein and
      mRNA transcripts for CYP1A1 were not detectable in resident peritoneal
      macrophages or peripheral blood monocytes. Examination of aromatic hydrocarbon
      receptor (AhR) levels in macrophage populations suggests that the ability of TCDD
      to induce metabolic enzymes in specific cell types correlates well with AhR
      expression. In vivo activation of macrophages, using either Bacillus of Calmette
      and Guerin, Mycobacterium tuberculosis (BCG) or polyinosinic:polycytidylic acid
      (Poly I:C), caused no significant alteration in the levels of induction of
      CYP1A1. ALDH-3 induction was similar in all macrophage populations examined.
      These studies indicate that macrophages, particularly those from portals of
      entry, may be induced to produce increased levels of specific enzymes, and the
      induction is dependent upon their maturational stage rather than their activation
      state. The metabolism of xenobiotics to toxic intermediates by immune cells and
      its role in immunosuppression are discussed.

PMID- 7503800
TI  - Naringenin: a weakly estrogenic bioflavonoid that exhibits antiestrogenic
      activity.
AB  - Treatment of immature 21-day-old female Sprague-Dawley rats with 17 beta
      estradiol (E2) (0.5 microgram/rat) caused a significant increase in uterine wet
      weight, DNA synthesis, progesterone receptor (PR) binding, and peroxidase
      activity. At doses as high as 40 mg/rat, the bioflavonoid naringenin did not
      cause a significant increase in any of these E2-induced responses. However, in
      rats cotreated with E2 (0.5 microgram/rat) plus naringenin (30 mg/rat); there was
      a significant decrease in E2-induced uterine wet weight, DNA synthesis, PR
      binding, and peroxidase activity, indicating that naringenin exhibits
      antiestrogenic activity in the immature rodent uterus. The binding of uterine
      nuclear extracts to a 32P-labeled estrogen responsive element (ERE) or
      progesterone responsive element (PRE) was determined using gel electrophoretic
      band shift assays. Incubation of [32P]ERE with uterine nuclear extracts from rats
      treated with naringenin or E2 resulted in the formation of estrogen receptor
      (ER):ERE complexes; a higher mobility complex was prominent in the extracts from
      E2-treated rats, whereas a lower mobility complex was observed using nuclear
      extracts from naringenin-treated animals. There was a significant decrease in the
      intensity of the E2-induced complex using nuclear extracts from rats treated with
      E2 plus naringenin. In contrast, transformed cytosol from control rats gave an
      intense ER:ERE complex, whereas the intensity of the band was decreased markedly
      using transformed uterine cytosol from treated rats. Formation of a PR:PRE
      complex was also determined using transformed uterine cytosol. Cytosol from E2
      treated rats gave an intense retarded band, whereas only weak bands were observed
      using cytosols from DMSO- (solvent), naringenin-, or naringenin plus E2-treated
      cells. The results of in vitro studies showed that 1 nM E2 increased (3- to 4
      fold) the growth of MCF-7 human breast cancer cells, whereas 1-1000 nM naringenin
      had no effect on cell proliferation. In cells cotreated with 1 nM E2 plus 1000 nM
      naringenin, there was a significant decrease in E2-induced cell growth. In MCF-7
      cells transiently transfected with a pS2 promoter-regulated luciferase reporter
      gene, naringenin exhibited weak estrogenic activity. In cells cotreated with 0.1
      or 1.0 microM naringenin plus 1 nM E2, naringenin inhibited E2-induced luciferase
      activity. The results of these studies confirmed that naringenin is a weak
      estrogen that also exhibits partial antiestrogenic activity in the female rat
      uterus and MCF-7 human breast cancer cells.

PMID- 7503803
TI  - Cytochrome P450 2A1, 2E1, and 2C9 cDNA-expression by insect cells and partial
      purification using hydrophobic chromatography.
AB  - High-level expression of three cloned cytochrome P450 enzymes was accomplished
      using the baculovirus-insect cell expression system. The amount of enzyme
      expression was enhanced by cell infections in the presence of medium-supplements
      containing hemin and by growth in suspension cultures. Human cytochromes P450 2E1
      and 2C9 and rat cytochrome P450 2A1 were partially purified from cell extracts
      using hydrophobic interaction and hydroxyapatite chromatography. The resulting
      enzymes were of estimated molecular masses similar to those reported previously
      and analyzed by PAGE. Reconstitution of enzyme activity resulted when the enzymes
      were incubated together with NADPH-cytochrome P450 reductase, phospholipid,
      NADPH, and appropriate substrates. The cytochrome P450 activity of the partially
      purified enzymes was comparable to that of the corresponding enzymes expressed in
      the vaccinia virus-Hep G2 system. These results provide evidence for a general
      means of obtaining cytochrome P450 enzymes for mechanistic, immunochemical, and
      biophysical investigations.

PMID- 7503802
TI  - In vivo selective modulation of tissue glutathione in a rat mammary carcinoma
      model.
AB  - Glutathione (GSH) is known to play a role in cellular sensitivity to some
      chemotherapeutic agents and to radiation. Depletion of cellular GSH has been
      demonstrated to result in enhanced toxicity of these drugs, and this approach is
      being explored in the clinic as a form of biochemical modulation, using the drug
      buthionine sulfoximine (BSO). The fact that some drug-resistant cell lines have
      increased glutathione levels, and that enhancing GSH concentrations in animal
      tissues protects against a variety of xenobiotic agents, suggest a different
      potential approach to improving anti-cancer therapy. We have examined the
      efficacy of the cysteine "pro-drug" L-2-oxothiazolidine-4-carboxylate (OTZ) at
      enhancing normal tissue versus tumor GSH. Animals were treated with OTZ or BSO,
      and the concentrations of GSH in normal tissues and tumor were measured. We found
      that the presence of the tumor itself decreased bone marrow GSH, but that OTZ
      significantly increased it in this setting. Interestingly, OTZ administration
      significantly depleted tumor GSH levels to the same level as did BSO. OTZ could
      offer a selective biochemical modulation of GSH.

PMID- 7503804
TI  - Enoxacin is an inducer of CYP1A2 in rat liver.
AB  - The induction of cytochrome P450 by enoxacin, ciprofloxacin, and ofloxacin was
      investigated in female Wistar rats. Animals were treated orally with daily doses
      ranging from 10 to 400 mg enoxacin per kg body wt, 400 mg ciprofloxacin, or 400
      mg ofloxacin per kg body wt for up to 7 days. Activities of methoxyresorufin O
      demethylase (MROD) and ethoxyresorufin O-deethylase (EROD) were determined
      fluorimetrically in hepatic microsomes. MROD activity was increased 2.6-fold
      after treatment with 100 mg enoxacin per kg body wt for 7 days. Lower doses of
      enoxacin did not induce MROD activity significantly. Antipeptide antibodies
      directed specifically against different rat cytochrome P450 enzymes demonstrated
      that CYP1A2, but not CYP1A1, was induced in rats treated with enoxacin. After
      ciprofloxacin or ofloxacin treatment, no induction of MROD or EROD activity was
      observed. Neither ciprofloxacin nor ofloxacin caused any change in CYP1A1 or
      CYP1A2 apoprotein levels. Further investigations with antipeptide antibodies
      showed that there was no induction of CYP2B1, CYP2B2, CYP2E1, CYP3A1, CYP3A2,
      CYP4A1, or CYP4A2 following treatment with enoxacin, ciprofloxacin, or ofloxacin.
      It is concluded that enoxacin, but not ciprofloxacin or ofloxacin, is an inducer
      of CYP1A2 in rat liver.

PMID- 7503805
TI  - (+)-bufuralol 1'-hydroxylation activity in human and rhesus monkey intestine and
      liver.
AB  - (+)-Bufuralol 1'-hydroxylation, a commonly used marker of hepatic CYP2D6
      activity, was investigated in human and rhesus monkey intestinal microsomes and
      compared with that in hepatic microsomes. The cumene hydroperoxide (CuOOH)
      mediated metabolism of (+)-bufuralol suggested that at least two enzymes were
      responsible for bufuralol 1'-hydroxylation in both human and monkey intestinal
      microsomes. In contrast, the kinetics of the CuOOH-mediated metabolism in human
      and monkey livers were monophasic. The Km values for the higher affinity
      component of the intestinal enzyme(s) of both species were similar to, while the
      corresponding Vmax values were much lower than, those obtained with the livers.
      Bufuralol metabolism mediated by NADPH exhibited biphasic kinetics and was less
      efficient than that observed in the presence of CuOOH in both human and monkey
      intestines, in agreement with the observations in the livers. Inhibition of
      bufuralol hydroxylase activity in the intestine and liver preparations from the
      same species by known CYP2D6 inhibitors/substrates was qualitatively similar.
      Quinidine was the most potent inhibitor of (+)-bufuralol 1'-hydroxylation in all
      tissues studied. Western immunoblots using anti-CYP2D6 peptide antibody revealed
      a protein band in human and monkey intestinal microsomes of the same molecular
      weight as that observed in the liver preparations. The intestinal CYP2D protein
      content appeared to be much less than that of liver, and correlated with the (+)
      bufuralol hydroxylase activity. Immunoinhibition studies indicated significant
      (up to 50%) inhibition of the CuOOH-mediated (+)-bufuralol metabolism in human
      and monkey intestines only by anti-CYP2D6, and not by anti-CYP2A6, or anti
      CYP2E1. Inhibition of the bufuralol 1'-hydroxylase activity by anti-rat CYP3A1
      was only slight (20%) in human, but marked (60-65%) in monkey intestinal
      microsomes. The hepatic metabolism of (+)-bufuralol in humans and monkeys was
      only inhibited (75%) by anti-CYP2D6, but not by anti-CYP3A1. Overall, the results
      suggest that (1) tissue and species differences exist in the catalysis of (+)
      bufuralol 1'-hydroxylation, and (2) CYP2D6-related enzymes are partially or
      primarily responsible for the bufuralol hydroxylase activity in human and monkey
      intestines or monkey liver.

PMID- 7503806
TI  - Cationic porphyrin derivatives as inhibitors of polyamine catabolism.
AB  - The effects of six cationic porphyrins on several enzymes involved in polyamine
      biosynthesis and catabolism have been examined. Both spermidine and spermine
      synthase were unaffected by the porphyrins at up to 2 mM. By contrast, ornithine
      and S-adenosylmethionine decarboxylase were inhibited by the nickel and cobalt
      derivatives of meso-tetrakis(N-methyl-4-pyridiniumyl)porphyrin (T4MPyP) with IC50
      values in the 10-100 microM region. Spermidine/spermine N1-acetyltransferase
      (SSAT) and polyamine oxidase (PAO) were highly sensitive to the six meso
      substituted cationic porphyrins tested, with Ki values as low as 6 nM for SSAT
      and 85 nM for PAO. These inhibitors may prove useful in defining the structural
      features of the active site of these enzymes.

PMID- 7503807
TI  - Protective effects of calcium channel blockers against free radical-impaired
      endothelial cell proliferation.
AB  - We have shown previously that the lipophilic calcium channel blockers exhibit
      membrane antioxidant activity. In the present study, when attached bovine aortic
      endothelial cells were exposed for 20 min to a low concentration of oxy-radicals
      generated from dihydroxyfumarate + Fe-ADP, no loss of glutathione or viability
      was detected; however, cell number, determined 48 hr later by the tetrazolium
      salt MTT assay, decreased to 45% of controls. Treatment of the cells for 1 hr
      with the calcium blockers (2-20 microM) prior to free radical exposure protected
      against the impaired cell growth in a concentration-dependent manner. The order
      of potency was nicardipine > or = nifedipine > or = verapamil > diltiazem, which
      appears to parallel their antioxidant potency. In addition, (+)-nicardipine, and
      its pharmacologically inactive isomer, (-)-nicardipine, were similarly effective.
      We conclude that it was the antioxidant activity of the calcium channel blockers
      that preserved the cell growth capacity against free-radical damage; such
      protective effects may contribute to their antiatherogenic effects.

PMID- 7503808
TI  - Genetic and molecular analysis of the rpoD gene from Lactococcus lactis.
AB  - A gene of Lactococcus lactis ATCC19435, the product of which is homologous with
      the principal sigma factors of Escherichia coli and Bacillus subtilis, was cloned
      and sequenced. The deduced amino acid sequence of the 340-residue protein and the
      upstream open reading frame of the cloned gene showed a homology to B. subtilis
      sigma 43 factor (the rpoD product) and DNA primase (the dnaE product),
      respectively, suggesting that L. lactis also has the rpoD operon. Surprisingly,
      introduction of the cloned L. lactis rpoD gene into a rpoD temperature-sensitive
      mutant of E. coli caused partial complementation.

PMID- 7503810
TI  - Vitamin E and exercise: aspects of biokinetics and bioavailability.

PMID- 7503809
TI  - Aortic stenosis, cesarean delivery, and epidural anesthesia.
AB  - A 23-year-old female was referred to the University of Arkansas for Medical
      Sciences at 32 weeks' gestation with a history of aortic stenosis following
      aortic valve replacement. Evaluation by echocardiography showed an approximately
      90 mmHg transvalvular pressure gradient. Pregnancy progressed to 36 weeks'
      gestation without problem, at which time the patient underwent cesarean section
      with lumbar epidural anesthesia. Invasive hemodynamic monitors were used to
      assess cardiac performance and as a guide for anesthetic management. The impact
      of aortic stenosis on pregnancy is discussed, as are management aspects of lumbar
      epidural anesthesia in such patients.

PMID- 7503811
TI  - Fusion of the dominant negative transcription regulator CHOP with a novel gene
      FUS by translocation t(12;16) in malignant liposarcoma.
AB  - The search for tumour-specific markers is one of the chief goals in cancer
      biology. We show that the translocation t(12;16)(q13:p11) in malignant myxoid
      liposarcoma can be a fusion of the CHOP dominant negative transcription factor
      gene with a novel gene, FUS, which can result in fusion of the FUS glycine-rich
      protein with the whole CHOP coding region. The data support the concept that
      protein fusion may commonly occur in solid tumours resulting in tumour-specific
      markers of potential clinical importance. The data also indicate the importance
      of transcription disruption in the pathogenesis of solid tumours.

PMID- 7503812
TI  - Bcl-2 functions in an antioxidant pathway to prevent apoptosis.
AB  - Bcl-2 inhibits most types of apoptotic cell death, implying a common mechanism of
      lethality. Bcl-2 is localized to intracellular sites of oxygen free radical
      generation including mitochondria, endoplasmic reticula, and nuclear membranes.
      Antioxidants that scavenge peroxides, N-acetylcysteine and glutathione
      peroxidase, countered apoptotic death, while manganese superoxide dismutase did
      not. Bcl-2 protected cells from H2O2- and menadione-induced oxidative deaths. Bcl
      2 did not prevent the cyanide-resistant oxidative burst generated by menadione.
      Two model systems of apoptosis showed no increment in cyanide-resistant
      respiration, and generation of endogenous peroxides continued at an inherent rate
      that was unaltered by Bcl-2. Following an apoptotic signal, cells sustained
      progressive lipid peroxidation. Overexpression of Bcl-2 functioned to suppress
      lipid peroxidation completely. We propose a model in which Bcl-2 regulates an
      antioxidant pathway at sites of free radical generation.

PMID- 7503813
TI  - EWS/Fli-1 chimeric protein is a transcriptional activator.
AB  - Fli-1, an ets related gene, was found to be rearranged in 75% of erythroleukemias
      induced by Friend murine leukemia virus. We have shown previously that the Fli-1
      gene codes for a sequence specific transcriptional activator which contains two
      autonomous transcriptional activation domains, one at the amino terminal region
      and the other at the carboxy terminal region. Recently human Fli-1 gene was shown
      to be involved in Ewing's sarcoma and related subtypes of primitive
      neuroectodermal tumors which share t(11;22) (q24;q12) chromosome translocation.
      In these tumors the carboxyl terminal region of Fli-1 was found to be fused with
      the amino terminal region of a putative RNA binding protein, EWS. Because part of
      the amino terminal transcriptional activation domain of Fli-1 was replaced with
      the amino terminal domain of the EWS (NTD-EWS) which shares homology with RNA
      polymerase II, it was speculated that NTD-EWS may interfere with RNA pol II
      function. Alternatively, NTD-EWS could also contribute to the transcriptional
      activation function of EWS/Fli-1 chimeric protein by providing either a
      modulatory/regulatory domain or a novel transcriptional activation domain. Here
      we show that EWS/Fli-1 chimeric protein functions as a transcriptional activator.
      Deletion analysis reveals that the EWS domain functions as a
      modulatory/regulatory domain for the transcriptional activation properties of the
      carboxy terminal transcriptional activation domain of EWS/Fli-1. We therefore
      propose that replacement of the amino terminal transcriptional activation domain
      of the Fli-1 protein with the regulatory domain of NTD-EWS results in the
      activation of the carboxy terminal transcriptional activation domain of Fli-1
      which may be the molecular mechanism involved in these human tumors.

PMID- 7503814
TI  - The irregular chiasm C-roughest locus of Drosophila, which affects axonal
      projections and programmed cell death, encodes a novel immunoglobulin-like
      protein.
AB  - The axonal projection mutations irregular chiasm C of Drosophila melanogaster
      comap and genetically interact with the roughest locus, which is required for
      programmed cell death in the developing retina. We cloned the genomic region in
      3C5 by transposon tagging and identified a single transcription unit that
      produces a major, spatially and temporally regulated mRNA species of
      approximately 5.0 kb. Postembryonic expression is strong in the developing optic
      lobe and in the eye imaginal disc. The gene encodes a transmembrane protein of
      764 amino acids with five extracellular immunoglobulin-like domains and
      similarity to the chicken axonal surface glycoprotein DM-GRASP/SC1/BEN. Both
      known irreC alleles reduce the level of transcription, whereas the roughestCT
      mutation disrupts the intracellular domain of the protein.

PMID- 7503815
TI  - Triangular fibrocartilage in asymptomatic subjects: investigation of abnormal MR
      signal intensity.
AB  - PURPOSE: To investigate the prevalence of abnormally high signal intensity of
      triangular fibrocartilage (TFC) tears on magnetic resonance (MR) images of
      asymptomatic subjects. MATERIALS AND METHODS: MR images of one wrist in 70
      asymptomatic volunteers (age range, 15-78 years) were evaluated for TFC high
      signal intensity. Findings at MR imaging and topographic parameters of each wrist
      studied were correlated with the subject's age. Any vertical or horizontal high
      intensity slits that reached the joint surface or evidence of a perforation was
      considered abnormal. RESULTS: Abnormally high TFC signal intensity was seen on
      images of 35 (50%) wrists. Further, a thin TFC was more often seen in subjects
      with positive variance, and positive ulnar variance and thin TFC were associated
      with high signal intensity. Age did not substantially affect the presence or
      absence of high signal intensity. CONCLUSION: Since TFC high signal intensity was
      frequently detected in these asymptomatic wrists, MR imaging cannot reliably be
      used to detect clinically meaningful abnormalities.

PMID- 7503816
TI  - Instrumental reports and effect of anticoagulants in a case of neutrophil
      agglutination in vitro.
AB  - BACKGROUND: The aim of this study was to investigate a case of EDTA-induced
      polymorphonuclear leukocyte (PMN) agglutination in vitro on Bayer Technicon H*1.
      Coulter Counter STKS and STKR analyzers. METHODS: Venous whole blood was
      anticoagulated with K3.EDTA, sodium citrate, lithius heparinate, acid citrate
      dextrose (ACD) and with two other anticoagulant mixtures containing citric acid
      theophylline-adenosine-dipyridamole (CTAD) or citrate-pyridoxal 5'-phosphate-tris
      (CPT). RESULTS: PMN agglutination, EDTA--but not temperature--dependent, was
      found by mere chance in an asymptomatic 48-year-old Caucasian male who did not
      show detectable PMN antibodies. Pseudoneutropenia without pseudoleukopenia was
      registered on H*1 exclusively in EDTA anticoagulated blood with a characteristic
      higher density PMN population on the BASO cytogram. Spuriously low white blood
      cell (WBC) counts and pseudoneutropenia appeared on STKR and STKS in EDTA
      anticoagulated blood, but signals on PMN agglutination were unsatisfactory.
      Accurate total and differential WBC counts were obtained in CTAD or CPT
      anticoagulated samples on the three analyzers. Heparin was the worst choice
      because it induced pseudothrombocytopenia and pseudoleukocytosis on STKR and
      STKS. CONCLUSIONS: Since PMN agglutination was not observed on peripheral smears
      and was undetected on EDTA anticoagulated samples processed immediately by H*1,
      the presence in vivo of PMN clumps should be excluded. Further hematological
      investigations will demonstrate in the long run whether the observed PMN
      agglutination in vitro is a transient occurrence in an apparently healthy subject
      not taking drugs at the time of observation.

PMID- 7503817
TI  - Intussusception: toward less surgery?
AB  - Since the 1950s, several large pediatric centers have used hydrostatic reduction
      with barium under fluoroscopic control as the treatment method of choice for
      ileocolic intussusception and have adopted rigid criteria for its management. One
      such rule has been that in order for an intussusception to be completely reduced,
      there must be adequate reflux of barium into the distal ileum. If this did not
      occur, it was assumed that the ileocolic intussusception had not been reduced,
      and the infant or child was taken straight to the operating room for laparotomy
      and surgical treatment. However, 10% of such intussusceptions were found to have
      reduced spontaneously. Needless to say, nonoperative management reduces morbidity
      and shortens hospitalization. From October 1985 through March 1991, 503 air
      contrast colon studies for suspected intussusception were performed on infants
      and children aged 2 days to 13 years (average, 16.8 months); 262 (52%) were
      normal, and 241 had an intussusception, 196 (81%) of which were reduced. The
      remaining 45 were operated on. In three patients (4 months to 2 years of age) the
      air enema reduced the intussusception from the colon without terminal ileum
      filling, but they all became asymptomatic immediately. For this reason they were
      not operated on; they were admitted and observed for 24 to 48 hours. Two of the
      three had recurrence of abdominal pain the next morning, but results of repeat
      air enemas were all normal (no intussusception observed, and normal terminal
      ileum filling).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503818
TI  - Suicide and mental disorders: a case-control study of young men.
AB  - OBJECTIVE: By means of the psychological autopsy method and a case-control
      design, the authors examined the association of specific mental disorders and
      comorbidity with suicide among young men. METHOD: Seventy-five men aged 18-35
      years whose deaths were adjudicated as completed suicides by coroners of greater
      Montreal and Quebec City were matched to 75 living young men for age,
      neighborhood, marital status, and occupation. For each subject in both groups a
      key respondent best acquainted with the subject was interviewed by clinicians
      using standardized schedules. Information from the coroner and medical records
      was also collected. Two experienced psychiatrists, blind to outcome, established
      best-estimate DSM-III-R diagnoses. RESULTS: Six-month prevalence rates for all
      axis I diagnoses for the suicide and comparison groups were 88.0% and 37.3%,
      respectively; major depression was present in 38.7% and 5.3%, alcohol dependence
      in 24.0% and 5.3%, psychoactive substance dependence in 22.7% and 2.7%.
      Borderline personality disorder was identified in 28.0% and 4.0%, respectively.
      Of the suicide subjects, 28.0% had at least two of the following disorders: major
      depression, borderline personality disorder, and alcohol or drug dependence; the
      rate was 0.0% among the comparison subjects. CONCLUSIONS: In young men, completed
      suicide is linked to specific mental disorders, namely, major depression,
      borderline personality disorder, and substance abuse. Comorbidity involving any
      of these disorders is frequently associated with completed suicide.

PMID- 7503819
TI  - Marijuana as an antiemetic drug: how useful is it today? Opinions from clinical
      oncologists.
AB  - OBJECTIVE: To determine the antiemetic drug preferences of practicing adult
      oncologists and to estimate the frequency of use of marijuana smoke as an
      antiemetic agent. DESIGN: Identical mailed questionnaire surveys on antiemetic
      preferences, distributed prior to approval of ondansetron. SAMPLE: Two groups of
      practicing clinical adult oncologists were surveyed. The first group (N = 120)
      consisted of every twentieth board-certified, American member of the American
      Society of Clinic Oncology culled from the 1990 ASCO membership directory in
      alphabetical order. The second group (N = 60) consisted of every adult clinical
      oncologist in metropolitan Washington, D.C. MEASUREMENTS/RESULTS: Completed
      surveys were returned by 141 (78%) physicians; the responses from both groups
      were almost identical (Wilcoxon Rank Sum Test). Marijuana (either as marijuana
      smoke or oral tetrahydrocannabinol) ranked ninth in order of preference for the
      treatment of mild to moderate nausea and vomiting, and sixth for the treatment of
      more severe symptoms induced by chemotherapy. Most (94 or 65%) respondents
      reported having prescribed marijuana or oral THC 10 times or less; only 5 (3.5%)
      had prescribed such drugs more than 100 times which represented for them about 1%
      of their average lifetime clinical patient load. The respondents who had
      prescribed marijuana in any form thought that it had effectively relieved post
      chemotherapy nausea or vomiting in 50% of patients. Unpleasant adverse effects
      were estimated to have occurred in 25% of treated patients. Only 8 (6%)
      respondents indicated that they would prescribe marijuana much more frequently-
      if there were no legal barriers associated with its medical use. CONCLUSION:
      Marijuana in any form was believed to be efficacious for 50% of patients with pre
      or post-chemotherapy nausea or vomiting. However, one of four patients who
      received it complained of bothersome adverse effects. At the time of the study,
      cannabis was prescribed or recommended relatively infrequently by American
      clinical oncologists (i.e., those who actually prescribed chemotherapy). Even if
      it was freely available and restrictions on its use liberalized, smokeable
      marijuana, according to responses given on this survey, would not be used much
      more frequently by American oncologists.

PMID- 7503820
TI  - How should dental bills be paid?

PMID- 7503821
TI  - Effect of aerosolized recombinant human DNase on exacerbations of respiratory
      symptoms and on pulmonary function in patients with cystic fibrosis. The
      Pulmozyme Study Group.
AB  - BACKGROUND: Respiratory disease in patients with cystic fibrosis is characterized
      by airway obstruction caused by the accumulation of thick, purulent secretions,
      which results in recurrent, symptomatic exacerbations. The viscoelasticity of the
      secretions can be reduced in vitro by recombinant human deoxyribonuclease I
      (rhDNase), a bioengineered copy of the human enzyme. METHODS: We performed a
      randomized, double-blind, placebo-controlled study to determine the effects of
      once-daily and twice-daily administration of rhDNase on exacerbations of
      respiratory symptoms requiring parenteral antibiotics and on pulmonary function.
      A total of 968 adults and children with cystic fibrosis were treated for 24 weeks
      as outpatients. RESULTS: One or more exacerbations occurred in 27 percent of the
      patients given placebo, 22 percent of those treated with rhDNase once daily, and
      19 percent of those treated with rhDNase twice daily. As compared with placebo,
      the administration of rhDNase once daily and twice daily reduced the age-adjusted
      risk of respiratory exacerbations by 28 percent (P = 0.04) and 37 percent (P <
      0.01), respectively. The administration of rhDNase once daily and twice daily
      improved forced expiratory volume in one second during the study by a mean (+/-
      SD) of 5.8 +/- 0.7 and 5.6 +/- 0.7 percent, respectively. None of the patients
      had anaphylaxis. Voice alteration and laryngitis were more frequent in the
      rhDNase-treated patients than in those receiving placebo but were rarely severe
      and resolved within 21 days of onset. CONCLUSIONS: In patients with cystic
      fibrosis, the administration of rhDNase reduced but did not eliminate
      exacerbations of respiratory symptoms, resulted in slight improvement in
      pulmonary function, and was well tolerated.

PMID- 7503822
TI  - Projecting patients' preferences from living wills: an invalid strategy for
      management of dementia with life-threatening illness.
AB  - OBJECTIVE: To examine variation in elders' choices of therapies in different
      clinical scenarios and to assess the validity of extending preferences expressed
      in scenarios of usual health, terminal illness, and coma to preferences in a
      scenario of moderately advanced Alzheimer disease. DESIGN: Questionnaire study of
      community-dwelling elders. SETTING: Houston metropolitan area. PARTICIPANTS: 218
      community-dwellers age 60 years and older. MEASUREMENTS: Responses regarding
      choices of 10 interventions in 4 scenarios. Interventions were: cardiopulmonary
      resuscitation (CPR), ventilator, total parenteral nutrition (TPN), i.v.
      medication and hydration, any medication, enteral feeding, dialysis, ICU
      admission, hospitalization, and antibiotics. Interventions were selected "never",
      "always," or a "trial of intervention to assess efficacy." Independent variables
      were responses in scenarios of usual state of health with a life-threatening
      illness, irreversible coma, and terminal illness causing pain. Dependent
      variables were responses in a scenario of moderately advanced Alzheimer disease
      with a life-threatening illness. Frequencies of responses were calculated using
      "never," "trial," and "always." Subsequently "trial" and "always" were collapsed
      into a category of "accepting intervention" for dichotomous analysis with
      "refusing intervention" (the "never" category). Logistic regression was used to
      assess validity of predicting responses in one scenario from the others. MAIN
      RESULTS: Preferences regarding medical therapies varied across scenarios (P <
      0.01). In the Usual Health scenario, all interventions were accepted more
      frequently than refused. In Terminal Illness and Coma scenarios, CPR, ventilator,
      TPN, enteral feedings and dialysis were refused more frequently than accepted. In
      the Alzheimer scenario, medications, ICU admission, hospitalization, and
      antibiotics were accepted more often than rejected. Trial was preferred to always
      in 90% of all choices across all scenarios. Preferences expressed in Terminal
      Illness, Coma, and Usual Health scenarios predicted choices in the Alzheimer
      disease scenario poorly. CONCLUSIONS: (1) Use of a scenario-based advance
      directive may be limited to the precise scenario described. (2) The common
      acceptance of interventions in the Alzheimer disease scenario differs from
      findings in earlier studies, possibly because of differences in populations
      surveyed or the stage of the disease described, highlighting the variability of
      preferences in this scenario. (3) Trial of intervention is attractive to many
      respondents, perhaps because it allows the advantage of potentially beneficial
      therapies without commitment to a course of therapy not leading to cure. (4)
      Results of this study should be interpreted in light of the study population,
      consisting largely of well educated, healthy Caucasians. Findings are likely not
      to be generalizable to other populations.

PMID- 7503823
TI  - A dispersed family of repetitive DNA sequences exhibits characteristics of a
      transposable element in the genus Lycopersicon.
AB  - A segment of DNA 5' to the transcribed region of an auxin-regulated gene, ARPI,
      from Lycopersicon esculentum Mill. cv. VFN8 contains a sequence with the
      structural characteristics of a transposable element. The putative element (Lyt1)
      is 1340 bp long, has terminal inverted repeats of approximately 235 bp and is
      flanked by 9-bp direct repeats. Lyt1 has a structure similar to the Robertson's
      Mutator (Mu) family from maize. The terminal inverted repeats are 80% AT-rich,
      are 96.6% identical, and define a larger family of repetitive elements. Southern
      analysis and genomic dot-blot reconstructions detected at least 41 copies of Lyt1
      hybridizing sequences in red-fruited Lycopersicon spp. (L. esculentum, L.
      pimpinellifolium and L. cheesmanii), and 2-8 copies in the green-fruited species
      (L. hirsutum, L. pennellii, L. peruvianum, L. chilense and L. chmielewskii).
      There were two to four copies in the Solanum spp. closely allied with the genus
      Lycopersicon (S. lycopersicoides, S. ochranthum and S. juglandifolium), while the
      more distantly related Solanum spp. showed little (one to two copies in S.
      tuberosum) to no (S. quitoense) detectable hybridization under stringent
      conditions. Linkage analysis in the F2 progeny of a cross between L. esculentum
      and L. cheesmanii indicated that at least six loci that hybridize to the Lyt1
      sequence are dispersed in the genome. Polymerase chain reaction and Southern
      analyses revealed that some red-fruited accessions and L. chmielewskii lacked
      Lyt1 5' to the transcribed region of ARPI. Subsequent sequence analysis indicated
      that only one copy of the 9-bp direct repeat (target site) was present,
      suggesting that transposition of the element into the ARPI gene occurred after
      the divergence of the red-fruited and green-fruited Lycopersicon species.

PMID- 7503824
TI  - CT diagnosis of blunt pancreatic trauma: importance of detecting fluid between
      the pancreas and the splenic vein.
AB  - OBJECTIVE: The purpose of this study was to determine the value of detecting
      fluid between the splenic vein and the pancreas on CT scans in the diagnosis of
      pancreatic injury after blunt abdominal trauma. MATERIALS AND METHODS: We
      retrospectively reviewed the abdominal CT scans of 10 patients with surgical- or
      autopsy-proved pancreatic injury after blunt abdominal trauma. The finding of
      fluid interdigitating between the pancreas and the splenic vein was then studied
      along with the reported CT features of pancreatic injury. These included
      intraperitoneal fluid, fluid in the lesser sac, extraperitoneal fluid, pancreatic
      edema or hematoma, and thickening of the anterior renal fascia. RESULTS: The CT
      scans of all 10 patients reviewed showed abnormalities suggesting pancreatic
      injury. Only 40% of patients showed all of the findings reported in the
      literature. Fluid interdigitating between the splenic vein and the pancreatic
      parenchyma was seen on CT scans in 90%. CONCLUSION: Our experience suggests that
      fluid between the splenic vein and the pancreas is a helpful CT finding for the
      diagnosis of pancreatic injury after blunt abdominal trauma. This finding was
      easy to recognize and in the proper clinical setting directs attention to
      additional subtle findings of pancreatic injury.

PMID- 7503825
TI  - Arsenic risk assessment.
AB  - We review recent publications by Hopenhayn-Rich et al. and Smith et al. regarding
      two critical issues in arsenic risk assessment: the role of methylation in the
      dose-response relationship and the role of internal cancers. Hopenhayn-Rich et
      al. applied simple linear regression to data from several studies to determine
      whether the percentage of inorganic arsenic in urine increases with increasing
      dose. Although their results failed to show a correlation between percent
      inorganic arsenic and urinary arsenic concentration, their evaluation does not
      demonstrate the absence of a methylation threshold because of the relatively low
      level of arsenic in urine and the use of grab samples in evaluating methylating
      capacity. Using data from an epidemiological study in Taiwan, Smith et al. have
      indicated that arsenic could be an important risk factor not only for skin cancer
      (the basis of the current EPA cancer slope factor), but also for several internal
      cancers including lung, liver, bladder, and kidney. We note the following
      deficiencies in the analysis of Smith et al: 1) the likely underestimated
      exposure estimate due to lack of consideration on nonwater sources of arsenic and
      the underestimate of water consumption, 2) lack of consideration of
      detoxification in estimating potential risks from low-level exposures typical of
      the U.S. population, and 3) lack of consideration of key differences,
      particularly nutritional differences, between the Taiwanese and U.S. populations
      that could affect potential risks.

PMID- 7503826
TI  - Orthodontic management of ankylosed permanent posterior teeth: a clinical report
      of three cases.
AB  - Ankylosed permanent posterior teeth may have a better prognosis than has been
      generally assumed. Three case reports offer testimony to the effectiveness of
      surgical luxation (loosening) with forced eruption induced by elastic force.
      Individual teeth, the occlusion, and the alveolar process may be preserved by
      early and aggressive treatment. The prognosis may be questionable, but the effect
      is preferable to premature extraction.

PMID- 7503827
TI  - Error in medicine.

PMID- 7503828
TI  - Heart rate alternans.

PMID- 7503829
TI  - Mathematical analysis of isovolemic hemodilution indicates that it can decrease
      the need for allogeneic blood transfusion.
AB  - BACKGROUND: The implementation of acute isovolemic hemodilution prior to surgical
      blood loss is a strategy used in an attempt to diminish the need for or obviate
      allogeneic transfusion and to avert the potential, attendant complications.
      Studies examining the efficacy of this technique have produced conflicting
      results. STUDY DESIGN AND METHODS: The present mathematical analysis was
      undertaken to resolve these conflicts by determining the efficacy of hemodilution
      and examining the influence of the variables affecting the outcome. Efficacy was
      defined as the volume of additional blood loss permitted and the volume and
      number of units of allogeneic blood saved from transfusion. A mathematical
      analysis evaluated the impact of circulating blood volume and initial and target
      hematocrits on the efficacy of isovolemic hemodilution. It was assumed that 1)
      hemodilution was completed before surgical blood loss; 2) transfusion of removed
      blood was begun when the target hematocrit was reached and lost surgical blood
      was replaced at a rate that maintained the target hematocrit; 3) allogeneic
      transfusion was begun after all autologous blood drawn was transfused; 4)
      normovolemia was maintained; and 5) a unit of allogeneic blood contains 175 mL of
      red cells. RESULTS: The analysis showed that isovolemic hemodilution can result
      in substantial additional allowable surgical blood loss that can diminish the
      need for or obviate allogeneic transfusion of red cells. Larger circulating blood
      volume, higher initial hematocrits, and lower target hematocrits increase the
      efficacy of hemodilution. Removal and isovolemic replacement of 1 to 2 units of
      blood provide minimal potential savings, as does hemodilution to a circulating
      (target) hematocrit of 30 percent. The extension of hemodilution to a hematocrit
      of (or below) 20 percent allows a disproportionately greater surgical blood loss
      and diminishes the need for allogeneic transfusion. It allows, for example, an
      additional 4.5 L of surgical blood loss, which represents a savings of 4 units of
      allogeneic blood when a patient with an initial blood volume of 5.0 L and a
      hematocrit of 45 percent undergoes isovolemic hemodilution to a hematocrit of 15
      percent. CONCLUSION: Isovolemic hemodilution can diminish or in some
      circumstances eliminate the need for allogeneic transfusion.

PMID- 7503830
TI  - Transcatheter closure of interatrial communications with a modified umbrella
      device.
AB  - OBJECTIVE: To show the institutional experience of closure of interatrial
      communications with a modified umbrella device. DESIGN: Descriptive study of all
      patients in whom transcatheter umbrella closure of interatrial communications has
      been attempted. SETTING: A tertiary referral centre. PATIENTS: 16 patients with
      17 interatrial communications of various types. INTERVENTIONS: Transcatheter
      placement of a modified Rashkind umbrella occluder. RESULTS: Two procedural
      failures due to venous access problems. Two placement failures needing early
      surgical repair. 13 successful placements in 12 patients. CONCLUSIONS: The
      modified Rashkind umbrella can successfully be used to close both iatrogenic and
      naturally occurring interatrial communications, particularly those present after
      the Fontan procedure.

PMID- 7503831
TI  - Laparoscopically assisted vaginal hysterectomy--gimmick or gain?

PMID- 7503832
TI  - Medical malapropisms (or A Stitch in Time Gathers No Moss)

PMID- 7503833
TI  - High cholesterol and mortality in older patients.

PMID- 7503834
TI  - Rickets and the crippled child: an historical perspective.

PMID- 7503835
TI  - Resurgence of rabies. A historical perspective on rabies in children.
AB  - Wildlife rabies in certain parts of the United States has been increasing. With
      greater urbanization, many areas have seen an influx of wild animals such as
      raccoons and foxes that are known wildlife reservoirs of rabies. Rabies
      encephalitis has been a fatal illness recognized by humans throughout history.
      The purpose of this review is to examine the history of rabies throughout the
      world to elucidate the evolution of popular and scientific knowledge of the
      disease in animals and humans. By examining this development from a pediatric
      perspective, we gain insight into the prevention and treatment protocols
      recommended for children today. Pediatricians need to include education about
      prevention and treatment of rabies exposures in their anticipatory guidance
      sessions with families.

PMID- 7503836
TI  - Institutional morality, authority, and ethics committees: how far should respect
      for institutional morality go?

PMID- 7503837
TI  - Pain relief.

PMID- 7503839
TI  - Strabismus in Williams syndrome.
AB  - PURPOSE: Williams syndrome is a rare genetic disorder, consisting of mental
      retardation, supravalvular aortic stenosis, elfin facies, and specific ocular
      findings, including strabismus. We undertook this study to evaluate the
      characteristics of the strabismus in Williams syndrome. METHODS: We examined 32
      patients with Williams syndrome to determine the prevalence and define the
      features of the strabismus in this patient population. RESULTS: Twenty-five of
      the 32 patients (78%) had strabismus, esotropia being the predominant form in 23
      of the 25 patients. Of the 19 patients with Williams syndrome who had infantile
      esotropia, seven had dissociated vertical deviation, ten had oblique dysfunction,
      and six had amblyopia. CONCLUSIONS: When the patients with Williams syndrome were
      compared to the general population, no statistically significant difference was
      found in the clinical characteristics of infantile esotropia between the two
      groups. Because of the high prevalence of esotropia in patients with Williams
      syndrome (72%) compared to the general population (0.1%), we postulate a genetic
      link between Williams syndrome and the hereditary form of infantile esotropia.

PMID- 7503838
TI  - Effect of high-dose ibuprofen in patients with cystic fibrosis.
AB  - BACKGROUND: Since the inflammatory response to chronic infection contributes to
      lung destruction in patients with cystic fibrosis, we hypothesized that anti
      inflammatory therapy might slow the progression of lung disease. METHODS: In a
      double-blind trial, 85 patients, 5 to 39 years of age, with mild lung disease
      (forced expiratory volume in one second [FEV1], > or = 60 percent of the
      predicted value) were randomly assigned to receive ibuprofen or placebo orally
      twice daily for four years. Doses were adjusted individually to achieve peak
      plasma concentrations of 50 to 100 micrograms per milliliter. Changes in
      pulmonary function, the percentage of ideal body weight, the chest-radiograph
      score, and the frequency of hospitalization were assessed. RESULTS: Patients
      randomly assigned to ibuprofen had a slower annual rate of change in FEV1 than
      the patients assigned to placebo (mean [+/- SE] slope, -2.17 +/- 0.57 percent vs.
      -3.60 +/- 0.55 percent in the placebo group; P = 0.02), and weight (as a
      percentage of ideal body weight) was better maintained in the former group (P =
      0.02). Among the patients who took ibuprofen for four years and had at least a 70
      percent rate of compliance, the annual rate of change in FEV1 was even slower (
      1.48 +/- 0.69 percent vs. -3.57 +/- 0.65 percent in the placebo group, P = 0.03),
      and this group of patients also had a significantly slower rate of decline in
      forced vital capacity, the percentage of ideal body weight, and the chest
      radiograph score. There was no significant difference between the ibuprofen and
      placebo groups in the frequency of hospitalization. One patient was withdrawn
      from the study because of conjunctivitis, and one because of epistaxis related to
      ibuprofen. CONCLUSIONS: In patients with cystic fibrosis and mild lung disease,
      high-dose ibuprofen, taken consistently for four years, significantly slows the
      progression of the lung disease without serious adverse effects.

PMID- 7503840
TI  - Neuropathies associated with monoclonal gammapathies.
AB  - There is increasing evidence that monoclonal proteins are implicated in the
      development of peripheral neuropathy. Approximately ten percent of patients with
      peripheral neuropathy of unknown cause have a monoclonal protein and this rate is
      significantly higher than prevalence rates of monoclonal protein in comparable
      segments of the general population. Extensive clinical, electrophysiological and
      immunopathological evidences indicate that peripheral neuropathy associated with
      monoclonal protein are heterogeneous, including: 1. the demyelinating,
      predominantly sensory neuropathies associated with anti-MAG antibodies; 2. the
      axonal, sensory neuropathies associated with anti-sulfatide and anti-chondroitin
      sulfate antibodies; 3. the motor neuropathies associated with anti-GM1
      antibodies. Patients with chronic polyneuropathies should be evaluated for
      underlying plasma cell dyscrasia.

PMID- 7503841
TI  - Open access echocardiography in management of heart failure in the community.
AB  - OBJECTIVE: To assess the value of an open access echocardiography service.
      DESIGN: Study of new open access service for general practitioners, who were
      invited to refer patients taking diuretics for suspected heart failure, untreated
      patients with symptoms of possible heart failure, and asymptomatic patients with
      risk factors for left ventricular systolic dysfunction. SETTING: Regional
      cardiology centre. SUBJECTS: 259 consecutive patients. MAIN OUTCOME MEASURES:
      Presence or absence of left ventricular systolic dysfunction and consequent
      changes in clinical management. RESULTS: 119 treated patients, 99 untreated
      patients, and nine asymptomatic patients were referred over five months. 32 were
      considered to be inappropriately referred. Among the treated patients, 31 had
      impaired left ventricular systolic function and five had valvular disease;
      angiotensin converting enzyme inhibitors were recommended for 34 of these
      patients. In addition, 53 were thought not to need diuretics. Eight untreated
      patients had impaired systolic function and six valvular disease. CONCLUSIONS:
      The service was well used by general practitioners and led to advice to change
      management in more than two thirds of patients.

PMID- 7503842
TI  - Consumption of olive oil and specific food groups in relation to breast cancer
      risk in Greece.
AB  - BACKGROUND: Experimental animal studies suggest that olive oil consumption, as
      contrasted to consumption of other fat types, does not enhance the occurrence of
      chemically induced mammary tumors, but human data are sparse. Furthermore,
      evidence is inconclusive concerning the role of food groups, as distinct from
      that of major nutrients, in the etiology of breast cancer in women. PURPOSE: This
      analysis was conducted to evaluate and quantify the effect of consumption of
      olive oil, margarine, and a range of food groups on the risk of breast cancer.
      METHODS: Data from a comprehensive, semiquantitative food-frequency questionnaire
      administered to 820 women with breast cancer and 1548 control women from the
      study base were used to calculate odds ratios (ORs) and X statistics of linear
      trend for the consumption of olive oil, margarine, and a series of food groups
      classified in quintiles. Adjustment for the effects of reproductive risk factors,
      energy intake, and mutual confounding influences was implemented through
      unconditional logistic regression modeling. RESULTS: Vegetable consumption and
      fruit consumption were independently associated with statistically significant
      reductions of breast cancer risk by 12% and 8%, respectively, per quintile
      increase; no significant associations were evident for the other food groups
      examined. Increased olive oil consumption was associated with significantly
      reduced breast cancer risk (OR = 0.75 [95% confidence interval = 0.57-0.98] for
      more than once a day versus once a day), whereas increased margarine consumption
      was associated with significantly increased risk (OR = 1.05 [95% confidence
      interval = 1.00-1.10] for an increment of four times a month). The olive oil
      association was apparently concentrated among postmenopausal women, but the
      relevant interaction term was not statistically significant; there was no
      suggestion of interaction with menopausal status for consumption of either
      vegetables, fruits, or margarine. CONCLUSIONS: Although major categories of
      macronutrients do not show significant associations with breast cancer risk in
      most studies, including the present one, vegetables and fruits are inversely,
      significantly, and strongly associated with this risk. There also is evidence
      that olive oil consumption may reduce the risk of breast cancer, whereas
      margarine intake appears to be associated with an elevated risk for the disease.

PMID- 7503843
TI  - Folic acid and the prevention of neural tube defects.

PMID- 7503845
TI  - Post-traumatic stress disorder and the lost memory syndrome.
AB  - A number of different symptoms may result as the reaction to severe stress. It is
      unjustified to assume that specific disorders, such as bulimia, multiple
      personality, borderline personality, etc., are caused by specific early childhood
      trauma. Fadism is harmful to the patient and the medical profession.

PMID- 7503844
TI  - Should patients positive for HIV infection receive pneumococcal vaccine?
AB  - Pneumococcal vaccination effectively reduces the incidence of invasive
      pneumococcal disease in normal subjects. Such invasive pneumococcal disease is
      100 times more common in patients with HIV infection than in healthy people, so
      it seems logical to target this group of patients for vaccination. Few clinics
      routinely vaccinate patients positive for HIV, despite Department of Health
      guidelines. This is because of uncertainty about the vaccine's efficacy in HIV
      disease. There are many reasons to suspect that the vaccine will fail to protect
      these patients, including the fact that antibodies alone may not be sufficient
      protection against all serogroups of Pneumococcus and the vaccine works in
      healthy people but not immunocompromised subjects. Vaccination of HIV positive
      patients may not be indicated, at least for the time being. The cost of
      vaccinating such patients in the absence of data showing efficacy may well be
      less than the cost of a necessarily large and lengthy trial. But the truth must
      be sought to end current indecision.

PMID- 7503846
TI  - Metabolic rates and nutrient requirements of sick dogs and cats.

PMID- 7503847
TI  - Conformal treatment of prostate cancer with improved targeting: superior prostate
      specific antigen response compared to standard treatment.
AB  - PURPOSE: Conformal radiation therapy (CRT) decreases the morbidity of prostate
      cancer treatment, but no published data attest to the improved ability of CRT to
      control disease. Therefore, we compared Prostate-Specific Antigen (PSA) response
      at 1 year among similarly staged patients treated by conformal techniques to
      those treated with conventional approaches, looking for an early indicator of
      tumor response. METHOD AND MATERIALS: Patients with locally advanced disease were
      treated by pelvic field followed by prostate field conedowns; those with early
      stage/low grade disease received only prostate field irradiation. Between
      October, 1987 and November, 1991, conventional treatments used rectangular beams
      with or without corner blocks. Neither urethrography nor immobilization casts
      were used for conventionally treated patients. Between April, 1989 and December,
      1992, conformal treatments have used rigid immobilization and Computed Tomography
      based, beams-eye-view field design. As such, our conformal approach allowed
      improved targeting. Median prescribed doses (minimal doses to the Planning Target
      Volume) were 70 Gy (66-73 Gy) and 70.2 Gy (64.8-75 Gy) for conventionally and
      conformally treated patients, respectively. Median daily fraction size was 1.8 Gy
      for conventional treatment and 2.0 Gy for conformal therapy. Baseline PSA data
      were available on 170 consecutive patients treated conformally and 90 consecutive
      patients treated conventionally. RESULTS: Among those receiving only prostatic
      field irradiation, 12-month PSA values returned to normal in 96% and 85% of
      conformally and conventionally treated patients, respectively, when normalization
      was defined as < or = 4 ng/ml (p < 0.03) and in 76% vs. 55% of patients when PSA
      normalization was defined as < or = 1.5 ng/ml (p < 0.02). Among those receiving
      pelvic irradiation prior to prostatic conedown, PSA normalization (< or = 4
      ng/ml) occurred in 82% and 61% (p < 0.01) of conformally and conventionally
      treated patients, respectively, and in 56% vs. 38% of patients when normalization
      was defined as < or = 1.5 ng/ml (p < 0.05). In a multivariate analysis,
      pretreatment PSA level (< or = 15 vs. > 15), and the use of conformal irradiation
      were statistically significant prognostic discriminants of PSA normalization at 1
      year while total irradiation dose, clinical stage, and the addition of pelvic
      fields were not significant. CONCLUSIONS: As measured by PSA normalization,
      conformal techniques with improved targeting produced responses that were
      significantly better than conventional techniques among patients treated with
      definitive irradiation. These results, coupled with our previously documented
      reduction of acute and chronic sequelae, support the continued use of CRT as a
      more effective method of treatment for prostate cancer.

PMID- 7503848
TI  - Dental practice parameters. Parameters for 12 oral health conditions. Adopted by
      the American Dental Association House of Delegates. October 1994.

PMID- 7503849
TI  - Impacted third molars.

PMID- 7503850
TI  - Unsuspected HIV infection presenting in first year of life.

PMID- 7503851
TI  - Comparison of intravenous ketorolac and alfentanil as supplements to propofol
      anesthesia for diagnostic panendoscopy.
AB  - STUDY OBJECTIVE: To determine if ketorolac tromethamine is an acceptable
      alternative to alfentanil as a supplement to propofol for diagnostic
      panendoscopy. DESIGN: Randomized, double-blind study. SETTING: University medical
      center. PATIENTS: 40 patients scheduled for panendoscopy and laryngeal tissue
      biopsy. INTERVENTIONS: Patients were randomly assigned to receive either
      alfentanil 14.5 micrograms/kg or ketorolac 1.0 mg/kg in a double-blind fashion, 5
      to 10 minutes before induction of general anesthesia. MEASUREMENTS AND MAIN
      RESULTS: Heart rate (HR) and noninvasive blood pressure (BP) were measured and
      recorded before and immediately after injection of the study drug, after
      laryngoscopy for the endotracheal tube placement, and after initiation of
      diagnostic panendoscopy. Bleeding in the operative field was rated by the
      endoscopist. Observation from discontinuation of the propofol infusion and
      nitrous oxide inhalation to eye opening, head lifting, and orientation to time
      and place was observed and recorded. The presence of stridor after extubation,
      and pulse oximeter-determined arterial blood oxyhemoglobin saturation immediately
      after extubation and 5 minutes later, were noted. In the recovery room, the
      ability to tolerate oral fluids, sit, stand, and walk were recorded.
      Supplementation with ketorolac provides faster recovery from anesthesia as
      evidenced by shorter time to eye opening, head lifting, and orientation to time
      and place. However, no intergroup differences were found in measured
      intraoperative variables (BP and HR following laryngoscopy, tracheal intubation,
      diagnostic panendoscopy, and tissue biopsy). Operative site bleeding was
      comparable in both groups. The variables reflecting street readiness and the
      incidence of nausea and vomiting were statistically comparable. CONCLUSION:
      Supplementation of propofol anesthesia with ketorolac is an efficacious
      alternative to supplementation with alfentanil. The faster recovery in the
      ketorolac group is explained by the mostly peripheral effect of this drug,
      whereas the slow decline in the alfentanil concentration at the effective site
      may be responsible for slower emergence from anesthesia.

PMID- 7503852
TI  - TEE and ventricular assist device insertion.

PMID- 7503853
TI  - Postsurgical nutritional support.

PMID- 7503854
TI  - Asystole and ischaemic brain injury.

PMID- 7503855
TI  - Musculoskeletal disability and rheumatology.

PMID- 7503856
TI  - Risk factors for heart disease.

PMID- 7503857
TI  - Medical costs then and now.

PMID- 7503858
TI  - Re: Radiology: the New York Hospital-Cornell Medical Center.

PMID- 7503859
TI  - Natural family planning in the 1990s.

PMID- 7503861
TI  - Aneurysm repair.

PMID- 7503860
TI  - Lithium augmentation.

PMID- 7503862
TI  - On being religious and a therapist.

PMID- 7503863
TI  - Cyclic fatigue and fracture in pyrolytic carbon-coated graphite mechanical heart
      valve prostheses: role of small crack in life prediction.

PMID- 7503864
TI  - The subject was radon.

PMID- 7503865
TI  - Canadian vs. U.S. health care: which system is 'best'?

PMID- 7503866
TI  - Strategies for anticoagulation prior to cardioversion.

PMID- 7503867
TI  - Minocycline and rheumatoid arthritis revisited.

PMID- 7503868
TI  - Transcatheter occlusion of cardiac defects.

PMID- 7503869
TI  - Parallel circuits and integrated experience.

PMID- 7503870
TI  - Folic acid and the prevention of neural tube defects. Folate has potential to
      cause harm.

PMID- 7503871
TI  - Evidence based medicine. Many questions cannot be answered by evidence based
      medicine.

PMID- 7503872
TI  - Handling scientific fraud. Serious allegations are hard to believe.

PMID- 7503873
TI  - Rationing. Local debate is needed.

PMID- 7503874
TI  - Transient femoral nerve palsy complicating preoperative ilioinguinal nerve
      blockade for inguinal herniorrhaphy.

PMID- 7503875
TI  - Transient femoral nerve palsy complicating preoperative ilioinguinal nerve
      blockade inguinal for herniorrhaphy.

PMID- 7503876
TI  - Sigmoidoscopy with a view.

PMID- 7503877
TI  - Human toxicity of PBDDs and PBDFs.

PMID- 7503878
TI  - FISH (fluorescent in situ hybridization): the second youth of cytogenetics.

PMID- 7503879
TI  - Request for additional information on Salmonella enteritidis isolates.

PMID- 7503880
TI  - Kodak Ektaspeed.

PMID- 7503881
TI  - Sleep apnea.

PMID- 7503882
TI  - Error in medicine.

PMID- 7503883
TI  - Clinical correlates in the deep tendon reflexes of the electrophysiology in the
      Lambert-Eaton myasthenic syndrome and myasthenia gravis.

PMID- 7503884
TI  - Hospital pharmacists.

PMID- 7503885
TI  - Promoting sexual abstinence in teens.

PMID- 7503886
TI  - Lipid solubility and epidural opioid efficacy.

PMID- 7503887
TI  - Questionable effectiveness of cricoid pressure in preventing aspiration.

PMID- 7503888
TI  - Inadequately trained dental surgeons.

PMID- 7503889
TI  - Open access echocardiography. Study's conclusion is misleading and cannot be
      generalised.

PMID- 7503890
TI  - Unsuspected HIV infection in first year of life. Minority with HIV infection must
      be identified.

PMID- 7503891
TI  - Continuous intravenous infusions of lorazepam versus midazolam for sedation.

PMID- 7503892
TI  - Glucose content of tracheal aspirates.

PMID- 7503893
TI  - Spontaneous TMJ dislocation.

PMID- 7503894
TI  - Cancer in children with primary or secondary immunodeficiencies.

PMID- 7503895
TI  - Regarding "what you did not know about the North American Symptomatic Carotid
      Endarterectomy Trial".

PMID- 7503897
TI  - Thrombosis in the antiphospholipid-antibody syndrome.

PMID- 7503896
TI  - The role of an ipsilateral carotid artery lesion on carotid subclavian bypass
      patency.

PMID- 7503898
TI  - Immigrants and tuberculosis.

PMID- 7503899
TI  - Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma.

PMID- 7503900
TI  - Age of early hominids.

PMID- 7503902
TI  - Endoscopic sclerotherapy for upper gastrointestinal bleeding due to Mallory-Weiss
      syndrome.

PMID- 7503901
TI  - Role of viral infections in the inception of childhood asthma and allergies.

PMID- 7503903
TI  - Strabismus in Williams syndrome.

PMID- 7503904
TI  - Laryngeal mask residual volume and damage during sterilization.

PMID- 7503905
TI  - Nonabandonment: medical ethics.

PMID- 7503906
TI  - Coenzymes Q9 and Q10 in skeletal and cardiac muscle in tumour-bearing exercising
      rats.
AB  - Physical exercise increases metabolic rate, and induces both adaptational
      biogenesis of mitochondria in skeletal muscle and an increase in antioxidant
      capacity. The onset of experimental anorexia and cachexia can be delayed by
      voluntary exercise. As skeletal muscle is the main target for cancer cachexia, we
      determined the levels of coenzymes Q9 and Q10 in skeletal muscle from tumour
      bearing exercising rats, and compared them to those of sedentary tumour-bearers
      and controls. Both tumour-bearing groups had increased levels of coenzymes Q9 and
      Q10 in the anterior tibial muscle (P < 0.05 for exercised animals). In the soleus
      muscle, only the tumour-bearing exercising animals demonstrated an increase in
      the levels of both coenzymes (P < 0.05). In cardiac muscle, the presence of
      tumour and exercise reduced the levels of coenzymes below that of sedentary
      controls. Exercise counteracted the anaemia in the tumour-bearing host (P <
      0.05). In conclusion, the increase in antioxidant capacity in skeletal muscle
      indicates a defence mechanism in the tumour-bearing hosts which is augmented by
      physical exercise.

PMID- 7503907
TI  - Pneumococcal vaccine for HIV patients. ...though vaccine's efficacy is unproved.

PMID- 7503908
TI  - Surgical bleeding and calcium antagonists. British aneurysm nimodipine trial
      reported improved clinical outcome with nimodipine.

PMID- 7503909
TI  - Treatment in the air. Patient might not have survived return to airport.

PMID- 7503910
TI  - Continuing medical education. The suppliers of continuing medical education may
      be the only ones to benefit.

PMID- 7503911
TI  - ABC of medical computing. The Internet.

PMID- 7503912
TI  - Importance of CT detection of retroperitoneal fluid in blunt pancreatic injury.

PMID- 7503913
TI  - Why is AOTA not using the ICIDH terminology?

PMID- 7503914
TI  - Oophorectomy at the same time as hysterectomy.

PMID- 7503915
TI  - The definition of pre-eclampsia.

PMID- 7503916
TI  - Chaos theory in obstetrics and gynaecology.

PMID- 7503917
TI  - Lesbian health care issues.

PMID- 7503918
TI  - Editing of human alpha-galactosidase RNA resulting in a pyrimidine to purine
      conversion.
AB  - During a study of the gene coding for alpha-galactosidase (EC 3.2.1.22), the
      lysosomal enzyme deficient in Fabry's disease, RT-PCR amplification of alpha
      galactosidase mRNAs obtained from three different tissues isolated from males
      revealed a substantial number of clones with a U to A conversion at the
      nucleotide position 1187. Such a modification of the coding sequence would result
      in an amino acid substitution in the C-terminal region (Phe396Tyr) of the enzyme.
      Neither PCR analysis of the genomic sequence nor the RT-PCR amplification of RNA
      obtained by in vitro transcription of the wild-type cDNA showed this change in
      the sequence. Multiple genes, pseudogenes are allelic variants were excluded.
      Hence, we propose RNA editing as a mechanism responsible for this base change in
      the alpha-galactosidase RNA.

PMID- 7503919
TI  - Heparin-coated cardiopulmonary bypass circuit for use during lung
      transplantation.

PMID- 7503920
TI  - Frequency and significance of major and minor clinical features of atopic
      dermatitis.

PMID- 7503921
TI  - An examination of therapeutic principles and practice in two forensic units.

PMID- 7503922
TI  - Mickie Grinevich: air evac nurse in World War II and Korea. Interview by Marlene
      Jezierski.

PMID- 7503923
TI  - Are calcium antagonists safe?

PMID- 7503924
TI  - Challenging the orthodoxy of insulin resistance.

PMID- 7503925
TI  - Natural family planning.

PMID- 7503926
TI  - Muscle sounds rediscovered.

PMID- 7503927
TI  - More on the language of anesthesia.

PMID- 7503928
TI  - ABC of medical computing. Manipulating and analysing data.

PMID- 7503929
TI  - Letter to the editor regarding Corn et al., IJROBP 32:325-330; 1995.

PMID- 7503930
TI  - Characteristics of false-positive exercise treadmill tests.

PMID- 7503931
TI  - The effects of chewing frequency and duration of gum chewing on salivary flow
      rate and sucrose concentration.
AB  - On ten separate occasions, unstimulated saliva was collected from 12 adults and
      then eight samples of saliva over a 20-min period while chewing, in random order,
      3 g of either Wrigley's Spearmint chewing-gum or gum-base at frequencies of 35,
      50, 70, 90, or 130 chews/min. With both stimuli, flow rates peaked in the first
      minute of stimulation and then fell with time. A repeated-measures analysis of
      variance showed that for both the gum and the gum-base, flow rates were
      independent of chewing frequency, except during the first minute with the chewing
      gum. The gum elicited a significantly higher flow rate over the first 4 min of
      chewing, while the base elicited a significantly higher flow rate over the 8-20
      min period of chewing. The sucrose concentration in saliva was also independent
      of chewing frequency. The salivary sucrose concentration peaked during the second
      minute of chewing (mean +/- SE = 424.7 +/- 20.0 mM) and the concentration then
      fell progressively with time. However, sucrose was still being released into
      saliva during the 15-20 min period of chewing (12.6 +/- 0.8 mM). Gum-base which
      had been chewed without access to saliva was softer than unchewed base but showed
      no change in filler content or a reduction in the average molecular weight. The
      decrease in hardness of the chewed gum-base may have resulted from improved
      mixing of heterogeneous phases and increased dispersion of plasticizing agents.

PMID- 7503932
TI  - Dual retinoblastoma-binding proteins with properties related to a negative
      regulator of ras in yeast.
AB  - The retinoblastoma protein (Rb) interacts with multiple cellular proteins that
      mediate its cellular function. We have identified nine polypeptides that bind to
      the T-binding domains of Rb using an Rb affinity resin. RbAp48 and RbAp46 are
      quantitatively the major Rb-associated proteins purified by this approach. RbAp48
      was characterized previously and was found to be related to MSI1, a negative
      regulator of Ras in the yeast Saccharomyces cerevisiae. Here we report the
      cloning and characterization of RbAp46. RbAp46 shares 89.4% amino acid identity
      with RbAp48. The internal WD repeats, which are found in a growing number of
      eukaryotic proteins, are conserved between RbAp46 and RbAp48. Like RbAp48, RbAp46
      forms a complex with Rb both in vitro and in vivo and suppresses the heat-shock
      sensitivity of the yeast RAS2Val-19 strains. We have also isolated the murine
      cDNA homologs of RbAp48 and RbAp46. Although both mRNA can be detected in all
      mouse tissues, their mRNA levels vary dramatically between different tissues. No
      significant differences were observed in the expression patterns of these genes
      in most tissues except thymus, testis, and ovary/uterus, in which 2-fold
      differences were observed. Interestingly, the mouse and human RbAp48 amino acid
      sequences are completely identical, and the mouse and human RbAp46 differ only by
      one conserved amino acid substitution. These results suggest that RbAp48 and
      RbAp46 may have shared as well as unique functions in the regulation of cell
      proliferation and differentiation.

PMID- 7503933
TI  - [The effects of salvia miltiorrhiza, polysaccharide sulphate, dextran 40 and
      mannitol on the viscoelasticity properties of red blood cell suspension].
AB  - In vitro, the effects of Dextran 40(DX40), mannitol, salvia miltiorrhiza and
      polysaccharide Sulphate (PSS) on the viscoelasticity properties of red cell
      suspensions were studied. The results demonstrated that when the concentration of
      the drugs increased, mannitol increased eta 5 x 96, eta 51 x 2, eta', eta" and
      G', and DX 40 increased the values of eta' eta" and G', but it had no obvious
      effect on eta 5 x 96 and eta 51 x 2; salvia miltiorrhiza and PSS had no obvious
      effect on eta 5 x 96, eta 51 x 2, eta', eta'' and G'. However, the average values
      of eta', eta'' and G' of Salvia miltiorrhiza and PSS groups were lower than those
      of DX 40 and Mannitol groups. Clinically, these four drugs in treatment doses
      might improve viscoelasticity properties of whole blood. For treating the
      ischemic cerebral vascular diseases and hyperviscosity syndromes, Salvia
      miltiorrhiza and PSS could be infused faster, but DX40 and mannitol should be
      infused slowly.

PMID- 7503934
TI  - Pseudosarcomatous fibromyxoid tumor of the urinary bladder and prostate:
      immunohistochemical, ultrastructural, and DNA flow cytometric analyses of nine
      cases.
AB  - Pseudosarcomatous fibromyxoid tumor of the genitourinary tract is a rare
      pathologic entity of hitherto unknown etiology that, because of the cellular
      pleomorphism and the infiltrative nature of the lesion, may be mistakenly
      diagnosed as sarcomatoid carcinoma or sarcoma. We retrospectively studied nine
      pseudosarcomatous fibromyxoid tumors involving the bladder and prostate to define
      characteristic parameters that may allow for accurate diagnosis. The study
      patients included four men and five women with a mean age of 48.7 years.
      Histologic analysis revealed myxoid lesions with a proliferation of spindle
      fibroblastic cells in a background of granulation tissue-type vascularity and
      inflammatory cells. Mitoses were infrequent and no atypical forms were found.
      Immunostaining was positive for vimentin and smooth muscle actin, and negative
      for S-100 protein, desmin, myoglobin, and keratin. Ultrastructurally, the lesion
      displayed fibroblastic and myofibroblastic cell features. Flow cytometric DNA
      content analysis revealed uniform DNA diploidy and a low S-phase fraction. All
      patients were alive and well with no evidence of disease after a mean follow-up
      of 4.8 years. In contrast, the sarcomatoid carcinomas and sarcomas of the urinary
      bladder and prostate that were used as controls occurred in older patients and
      had more frequent mitoses with atypical forms, tumor-type necrosis, and different
      immunostaining profiles; they were preponderantly aneuploid or diploid with high
      S-phase fraction. Awareness of the clinicopathologic and biologic characteristics
      of these lesions is necessary to ensure their accurate diagnosis and to prevent
      unnecessary radical therapy.

PMID- 7503935
TI  - Small cell osteosarcoma of bone: an immunohistochemical study with differential
      diagnostic considerations.
AB  - Seventy-nine cases of small round cell tumors involving bone were studied in an
      attempt to learn whether the immunohistochemical features of the lesions might
      allow distinction of small cell osteosarcoma from other potential differential
      diagnostic considerations, including Ewing's sarcoma, atypical Ewing's sarcoma,
      primitive neuroectodermal tumor, mesenchymal chondrosarcoma, lymphoma, and the
      Askin tumor. The tissues studied were all formalin-fixed, decalcified, paraffin
      sections from patients between the ages of 16 and 48 years. With one exception (a
      small cell osteosarcoma), none of the lesions was cytokeratin positive. Moreover,
      none of the lesions was epithelial membrane antigen, desmin, factor VIII-related
      antigen, synaptophysin, or Leu-M1 positive. Accordingly, strong positivity for
      these antibodies in a majority of tumor cells should prompt inclusion of tumor
      types other than those listed above in the differential diagnosis. Vimentin
      positivity was seen in a majority of the tumors studied irrespective of
      histologic type. Scattered tumor cells (< 25%) showed positivity with antibodies
      to muscle-specific actin and smooth muscle actin in several of the different
      tumor types studied. No lesions other than lymphoma were leukocyte-common antigen
      (LCA) positive; all but two lymphomas were LCA positive, while all but one
      lymphoma were L26 positive. One (lymphoblastic) lymphoma was LCA and L26
      negative. S-100, neuron-specific enolase, and Leu-7 did not prove to be specific
      for "neural-associated" tumors, but rather appeared in some small cell
      osteosarcomas, Ewing's sarcomas, atypical Ewing's sarcomas, primitive
      neuroectodermal tumors, mesenchymal chondrosarcomas, lymphomas, and Askin tumors.
      Antibody to cell surface antigen HBA71 was positive in three Ewing's sarcomas
      (two typical and one atypical) and negative in small cell osteosarcoma (three
      cases), mesenchymal chondrosarcoma (two cases), and lymphoma (one case). While
      some guidance may be derived from analysis of immunohistochemical staining
      patterns in a given lesion, the results reported in the present study do not
      suggest that routine immunohistochemistry alone will permit distinction of these
      small cell tumors of bone from one another. The value of immunohistochemical
      studies appears to lie particularly in the use of antibodies to LCA and S-100
      protein to distinguish lymphoma and mesenchymal chondrosarcoma, and perhaps
      antibody to HBA71 to distinguish neural family lesions (such as Ewing's sarcoma),
      from other small cell tumors, such as small cell osteosarcoma.

PMID- 7503936
TI  - Structure and chromosomal localization of the gene encoding the human myelin
      protein zero (MPZ).
AB  - We describe the cloning, characterization, and chromosomal mapping of the human
      myelin protein zero (MPZ) gene. The gene is about 7 kb long and consists of six
      exons corresponding to the functional domains. All exon-intron junction sequences
      conform to the GT/AG rule. The 5'-flanking region of the gene has a TA-rich
      element (TATA-like box), two CAAT boxes, and a single defined transcription
      initiation site detected by the primer extension method. The gene for human MPZ
      was assigned to chromosome 1q22-q23 by spot blot hybridization of flow-sorted
      human chromosomes and fluorescence in situ hybridization. The localization of the
      MPZ gene coincides with the locus for Charcot-Marie-Tooth disease type 1B,
      determined by linkage analysis.

PMID- 7503937
TI  - Gene encoding the collagen type I and thrombospondin receptor CD36 is located on
      chromosome 7q11.2.
AB  - The human CD36 is a member of a gene family of structurally related glycoproteins
      and functions as a receptor for collagen type I and thrombospondin. CD36 also
      binds to red blood cells infected with the human malaria parasite Plasmodium
      falciparum. In the present study, the CD36 gene was assigned to chromosome 7 by
      using the polymerase chain reaction with DNA from human-hamster somatic cell
      hybrids. Furthermore, the use of a CD36 genomic probe has allowed the
      localization of the CD36 locus to the 7q11.2 band by fluorescence in situ
      hybridization coupled with GTG-banding.

PMID- 7503938
TI  - Factors affecting production of antibodies to prostate antigens by in vitro
      primed human splenocytes.
AB  - Efficiency of immunization of splenocytes in vitro by three kinds of prostate
      antigen has been studied. Intact cells of the human prostate cell line LNCaP, a
      membrane preparation (PMA) of LNCaP cells, and prostate specific antigen (PSA)
      were used as antigens. Three different schemes of in vitro immunization were
      tested: male spleen cells vs female; single donor spleen cells vs. mixed
      lymphocyte culture (MLC); addition of exogenous IL-2 vs. no lymphokine addition.
      The supernatant antibodies were tested for reactivity to the immunizing antigen
      by ELISA. Subsequently hybridomas were generated by fusing the primed lymphocytes
      to a heteromyeloma cell line, K6H6/B5. Only antigen specific IgM responses could
      be detected. Intact LNCaP cells induced the highest responses from mixed
      lymphocyte cultures. PMA also induced the highest responses from mixed lymphocyte
      cultures of male origin, whereas both single donor and mixed donor spleen cell
      cultures of female origin responded to PMA. However, anti-PMA responses by mixed
      lymphocyte cultures of female cells were significantly augmented by addition of
      IL-2. PSA only induced specific responses from mixed female splenocyte cultures
      supported with IL-2. Several anti-PMA and -PSA antibodies were generated after
      somatic fusion of the in vitro primed cells. Two monoclonal IgG antibodies from
      LNCaP primed spleen cells could be competitively inhibited with tumor membrane
      antigen.

PMID- 7503939
TI  - Production and characterization of monoclonal antibodies recognising defined
      regions of the human oestrogen receptor.
AB  - Mouse monoclonal antibodies were raised against the N-terminal (amino acids 151
      165) and the very C-terminal (amino acids 578-595) regions of the human oestrogen
      receptor (hER). These antibodies recognise the hER by enzyme-linked immunosorbent
      assay, immunocytochemistry, immunoblotting, immunoprecipitation and gel
      retardation assays. The presence of hER is used prognostically in human breast
      cancer. We have tested the reactivity of our monoclonal antibodies on breast
      cancer sections, comparing with the commonly used Abbott rat monoclonal antibody
      H222. These studies show that the two monoclonal antibodies described here are
      highly versatile and will be useful tools for in vivo and in vitro studies of hER
      function. Furthermore, we show that the corresponding epitopes can be used as
      molecular "tags" for heterologous proteins and offer a powerful means of
      purifying and/or characterizing over-produced fusion proteins containing these
      regions.

PMID- 7503940
TI  - Characterization of a new monoclonal antibody F4 detecting cell surface epitope
      and P-glycoprotein in drug-resistant human tumor cell lines.
AB  - Using viable adriamycin resistant human ovarian carcinoma cells 2780AD and
      colchicine resistant human oral epidermoid carcinoma cells KB-24 as the immunogen
      in primary and subsequent i.p. immunizations, followed by i.v. boostings with
      crude plasma membranes of 2780AD, KB-24, Chinese hamster lung cells resistant to
      vincristine DC-3F/VCRd-5L, and resistant to daunorubicin DC-3F/DMXX, we have
      generated a new murine monoclonal antibody (McAb), designated F4, of IgG1
      isotype. McAb F4 reacted strongly with a cell surface epitope of drug resistant
      cells and insignificantly with their drug sensitive counterparts. Cell surface
      localization of F4 epitope was determined by immunofluorescence and laser
      scanning confocal imaging system. Results obtained from immunoprecipitation and
      immunoblot analyses using F4 and mdr1 P-glycoprotein specific McAb JSB-1
      demonstrated the reactivity of P-glycoprotein with F4. These results along with
      those obtained from competitive binding-inhibition, chemical modification, and
      enzyme hydrolysis, revealed that McAb F4 detects an extracellular epitope of P
      glycoprotein, and is different from other major McAbs directed against P
      glycoprotein, e.g. C219, MRK16, JSB-1, HYB-241 and C494. Deduced from the
      putative structure of mdr1 protein and its orientation in cell membrane, it is
      proposed that F4 epitope is localized in or near the 3rd, and/or 6th
      extracellular transmembrane loops of P-glycoprotein.

PMID- 7503941
TI  - Characterization of murine monoclonal antibodies directed against the submembrane
      protein p17 of HIV-1.
AB  - Monoclonal antibodies (MAbs) were raised against the gag protein of human
      immunodeficiency virus type 1 (HIV-1). The reactivity of the selected Mabs with
      the matrix protein p17 of HIV-1 were investigated in several tests, i.e. ELISA,
      immunostaining of Western blots, and alkaline phosphatase anti-alkaline
      phosphatase immunocytochemistry (APAAP). All three Mabs reacted exclusively with
      HIV-1 and showed specific binding to the virus surface in pre-embedding immuno
      electron-microscopy and useful as diagnostic agents. In an "in vitro" cultivation
      experiment the MAbs showed antiviral activity in concentrations in the range of
      25-100 micrograms/ml. No binding region could be defined using overlapping
      peptides consisting of the p17 protein sequence of HIV-1 in an epitope mapping
      system and therefore we concluded, that the MAbs recognize a conformational
      epitope.

PMID- 7503942
TI  - Synthetic peptide-generated monoclonal antibodies to transforming growth factor
      beta 1.
AB  - Using a synthetic peptide with the amino acid sequence corresponding to residues
      78-109 of human TGF-beta 1 (A78/109 peptide) as an immunogen, we generated and
      characterized monoclonal antibodies (Mabs) against transforming growth factor
      beta 1 (TGF-beta 1). Spleen cells from a mouse immunized with carrier-free
      A78/109 peptide were fused with a myeloma cell line, P3U1. Two hybridoma cell
      lines were selected with A78/109 peptide used as the antigen, and the Mabs were
      designated as 3H10 and 4C10. Mab 4C10 recognized TGF-beta 1 only in
      immunoblotting analysis, but not in ELISA. In contrast, Mab 3H10 recognized it in
      not only ELISA but also immunoblotting analysis. Neither Mab was capable of
      recognizing both porcine TGF-beta 2 and chicken TGF-beta 3, and, therefore, both
      Mabs were TGF-beta 1 specific. From the results of epitope-mapping analysis, both
      Mab 3H10 and Mab 4C10 recognized the 78-87 portion of TGF-beta 1. The epitope
      recognized by Mab 4C10 was mapped specifically to amino acids 85-87. These
      results suggest that the region within 78-87 is exposed in the dimeric TGF-beta 1
      and is one of the antigenic determinants in this molecule.

PMID- 7503943
TI  - A monoclonal antibody to the alpha 2 integrin subunit cross-reacts with RGD
      dependent epitopes in fibrinogen.
AB  - Monoclonal antibodies were raised against platelet integrins purified by affinity
      chromatography. Two monoclonal antibodies (5C5 and 3H8) reacted with the purified
      alpha 2 subunit of VLA-2 in Western blotting. The monoclonal antibody 3H8 also
      reacted with fibrinogen in Western blots and in ELISA tests. CNBr fragmentation
      of the alpha chain of fibrinogen generated two peptides which were still
      recognized by this monoclonal antibody in Western blotting. N-terminus sequencing
      of these two fragments showed that they were non-overlapping fragments of the
      fibrinogen alpha-chain with as only common epitope an RGD(F)/RGD(S) sequence. Dot
      blots and ELISA tests showed that the antibody 3H8 also recognized, however with
      lower affinity, fibronectin and collagen IV, which are RGDS containing
      extracellular matrix proteins. The assumption that Mab 3H8 recognizes an RGD
      sequence, was further supported by the findings that the binding of Mab 3H8 to
      fibrinogen was partially inhibited by RGDF containing peptides and that the
      antibody was able to inhibit platelet aggregation.

PMID- 7503945
TI  - In vitro activation of leukaemic B cells by interleukin-4 and antibodies to CD40.
AB  - Chronic lymphocytic leukaemia (CLL) B cells have the phenotype of mature,
      partially activated B cells, but are relatively resistant to stimulation through
      cell-surface receptors with agents such as antibodies to immunoglobulin M. In the
      present study we have shown that culture of CLL cells with interleukin-4 (IL-4)
      and antibodies to CD40 caused significant DNA synthesis as assessed by
      incorporation of thymidine. This effect was largely mediated by antibody binding
      to CD40, a molecule known to induce B-cell activation and to mediate survival
      signals to germinal centre B cells. Epstein-Barr virus (EBV) infection of CLL
      cells stimulated with IL-4 and anti-CD40 did not affect the state of
      differentiation of the cell, augment the proliferative capacity, prolong cell
      survival or cause virus-driven immortalization.

PMID- 7503944
TI  - Expression of immune associated surface antigens of keratinocytes in human
      papillomavirus-derived lesions.
AB  - The expression of immune associated surface antigens of keratinocytes was studied
      in human papillomavirus (HPV) derived lesions in order to determine whether HPV
      types have a regulatory role in the pathogenesis of papillomas. A series of
      cutaneous and mucosal lesions were immunolabeled with monoclonal antibodies to
      the major histocompatibility complex class 1 (beta 2-microglobulin) and 2 (HLA-DR
      antigens), intercellular adhesion molecule (ICAM-1) and glycoprotein CD36 (OKM5)
      as well as CD1a (Langerhans cells), CD4, CD8 (T cells) and CD11a (LFA1 antigen).
      Testing for the presence of HPV was carried out by in situ hybridization with
      biotinylated probes for viral DNA detection and typing. We observed a drastic
      reduction or a loss of beta 2-microglobulin by keratinocytes from cutaneous
      lesions in correlation with the disappearance of Langerhans cells. Only mild
      alterations were observed in mucosal lesions. HLA-DR expressed by keratinocytes
      was only detected in condylomas and laryngeal papillomas and was usually
      associated with a dense inflammatory reaction. This HLA-DR expression may be
      correlated with an up-regulation of ICAM-1 and the presence of LFA1 positive
      leukocytes, mainly of CD8 phenotype, in the epithelium. CD36 was detected on
      differentiated keratinocytes of all lesions; its expression seems related to the
      proliferation state of the lesions and probably does not represent an immune
      marker. The different reactivity patterns observed in cutaneous and mucosal
      lesions may reflect: 1. different roles for mucosal and cutaneous HPV types in
      the induction of immunoregulatory surface antigens of keratinocytes, or 2. the
      changing nature of the cytokines released by mononuclear cells and infected
      keratinocytes in these lesions.

PMID- 7503946
TI  - Recognition of peptide epitopes of the 16,000 MW antigen of Mycobacterium
      tuberculosis by murine T cells.
AB  - The T-cell repertoire to a prominent immunogen of Mycobacterium tuberculosis has
      been investigated on the assumption that differences in epitope specificity could
      influence the protective and pathogenic host reactions. Proliferative responses
      of lymph node and spleen cells to overlapping peptides, spanning the entire
      sequence of the 16,000 MW protein antigen were analysed in C57BL/10 and B10.BR
      mice. Following footpad priming and in vitro challenge with homologous peptide,
      12 out of the 14 peptides tested were found to be immunogenic. However, only two
      peptides of residues 31-40 and 71-91 stimulated strong proliferative responses of
      T cells from mice which had been presensitized with either killed or live M.
      tuberculosis organisms; another three peptides were only weakly stimulatory.
      These epitopes have been immunodominant in both H-2b and H-2k mouse strains,
      indicating the genetically permissive nature of their recognition. Furthermore,
      both major immunodominant epitopes were found to be species specific for the M.
      tuberculosis complex and therefore potentially suitable for the early diagnosis
      of tuberculous infection.

PMID- 7503947
TI  - Endogenous tachykinins play a role in IL-1-induced neutrophil accumulation:
      involvement of NK-1 receptors.
AB  - Pretreatment of mice with capsaicin resulted in approximately 40% inhibition of
      the polymorphonuclear leucocyte (PMN) influx elicited by interleukin-1 (IL-1)
      injected into a murine air-pouch. This inhibition was mimicked by two selective
      antagonists of neurokinin-1 (NK-1) tachykinin (TK) receptors, i.e. CP-96,345 and
      RP-67,580, but not by the inactive enantiomer RP-68,651. A selective NK-2
      antagonist, SR-48,968, was inactive. The natural peptide, substance P (SP), and a
      selective NK-1 agonist, (Sar9)SP, induced PMN infiltration into the murine air
      pouch, whereas a selective NK-2 agonist, (beta Ala8)NK-A(4-10), was ineffective.
      Moreover, SP-induced PMN accumulation was prevented by co-administration of RP
      67,580 and CP-96,345, but not by RP-68,651. These findings suggest that the
      release of an endogenous TK, possibly SP, may occur following IL-1 injection in
      vivo, indicating a contributory role for neuropeptides in the PMN migration
      elicited by this cytokine. The action of selective agonists and antagonists
      suggests the involvement of NK-1 receptors.

PMID- 7503948
TI  - Anti-CD14 antibodies reduce responses of cultured human endothelial cells to
      endotoxin.
AB  - Lipopolysaccharide (LPS) activates both myeloid and endothelial cells. Whereas
      CD14 has been shown to be involved in LPS recognition by myeloid cells, the
      mechanism responsible for the strong response of endothelial cells to LPS remains
      to be elucidated. The role of CD14 in this process was studied using CD14
      specific antibodies (Ab). Anti-CD14 Ab inhibited LPS-induced interleukin-6 (IL-6)
      release and E-selectin expression by cultured human umbilical vein endothelial
      cells (HUVEC). Messenger RNA encoding IL-6 and E-selectin was reduced in
      parallel. The inhibitory effect of anti-CD14 Ab was epitope dependent, maximal at
      low LPS concentrations and dropping with increasing LPS doses. Anti-CD14 Ab did
      not affect endothelial cell activation induced by IL-1 beta, tumour necrosis
      factor-alpha (TNF-alpha) and phorbol 12-myristate 13-acetate (PMA). IL-6 release
      and E-selectin expression of HUVEC were strongly reduced when LPS activation was
      performed in the absence of serum, indicating involvement of serum components in
      LPS activation of HUVEC. Nevertheless, anti-CD14 Ab also blocked LPS-induced
      HUVEC activation in the absence of serum. Although the role of serum components
      in LPS activation remains to be elucidated, CD14 seems to be a key mediator in
      LPS-induced activation of endothelial cells.

PMID- 7503949
TI  - Serum-independent binding of lipopolysaccharide to human monocytes is trypsin
      sensitive and does not involve CD14.
AB  - The nature of the binding sites for lipopolysaccharide (LPS) on human monocytes
      was investigated using fluorescein isothiocyanate (FITC)-labelled LPS from
      Salmonella minnesota R595 (ReLPS). In the absence of serum, ReLPS bound to
      monocytes and this interaction was trypsin sensitive. A concentration of 0.1
      mg/ml resulted in a 90% loss of LPS binding, while low concentrations increased
      this binding. Trypsin-treated monocytes recovered FITC-ReLPS binding after 20 hr
      culture, which was abrogated in the presence of cycloheximide and actinomycin D.
      This showed that de novo protein and mRNA synthesis were essential. A number of
      different proteins have been implicated in cellular binding of LPS to monocytes.
      In this paper we show that CD14 is not involved in direct binding of FITC-ReLPS
      to monocytes, since anti-CD14 monoclonal antibody (mAb) (3C10) and removal of
      most of cell-surface CD14 by phosphatidylinositol-specific phospholipase C did
      not prevent FITC-ReLPS binding. Furthermore, LPS also bound to CD14-deficient
      cells from a patient with paroxysmal nocturnal haemoglobinuria (PNH). FITC-ReLPS
      binding was not mediated by the CD11/CD18 complex since mAb to the alpha and beta
      chains of the CD11/CD18 complex did not alter the binding of FITC-ReLPS to cells.
      These observations indicate that ReLPS may interact with monocyte membrane
      protein(s) in the absence of serum. This binding site(s) for LPS might be
      different from those previously described by others.

PMID- 7503951
TI  - Role of nitric oxide synthesis in salt-sensitive hypertension in Dahl/Rapp rats.
AB  - Nitric oxide is a potent endogenous vasodilator that regulates arterial tone. A
      family of nitric oxide synthases uses L-arginine and L-homoarginine
      stereospecifically as substrates for nitric oxide production in vivo. By
      preventing expression of inducible but not constitutive nitric oxide synthases,
      glucocorticoids differentiate which enzyme in this family is the predominant
      source of nitric oxide generation in a given situation. We proposed that
      defective production of nitric oxide produces salt-sensitive hypertension in the
      Dahl/Rapp rat. Plasma concentrations of L-arginine, citrulline, and ornithine of
      salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats on 8% sodium chloride chow
      for 1 week did not differ. However, intravenous infusion of L-arginine and L
      homoarginine, but not D-arginine, increased urinary excretion of nitrate, the
      degradation product of nitric oxide, and simultaneously lowered blood pressure in
      hypertensive SS/Jr rats. Oral L-arginine also prevented development of
      hypertension and increased urinary excretion of cyclic GMP and nitrate in these
      rats. Dexamethasone, in a dose that prevented hypotension from parenteral
      injection of lipopolysaccharide, completely prevented the increase in excretion
      of cyclic GMP and nitrate, and hypertension resulted despite concomitant
      treatment with L-arginine. These studies supported an important role of
      dexamethasone-suppressible nitric oxide synthesis in the prevention of salt
      sensitive hypertension in the Dahl/Rapp rat.

PMID- 7503950
TI  - Expression and function of CD5 and CD28 in patients with rheumatoid arthritis.
AB  - To assess the role of CD5 and CD28 in the pathogenesis of the decreased cellular
      immune function in patients with rheumatoid arthritis (RA) we analysed the
      expression and function of these T-cell surface molecules. The expression of CD5
      as well as of CD28 in synovial and peripheral blood T cells was similar to that
      of control T cells. Monoclonal antibodies (mAb) directed at CD28 and CD5 were
      able to provide an accessory signal to anti-CD3 activated T cells both from the
      synovial fluid and from the peripheral blood. However, the proliferation induced
      by anti-CD3 mAb in conjunction with anti-CD5 or anti-CD28 mAb was always higher
      in peripheral blood (PB) T cells compared to the paired synovial fluid T cells.
      After simultaneous ligation of CD5 and CD28, proliferation was induced in the PB
      T cells. However, when compared to control PB T cells, this proliferation was
      significantly lower in the RA patients. Purified normal memory (CD45RO+) T cells
      proliferated less strongly than naive (CD45RA+) T cells, but no difference was
      observed between rheumatoid and normal memory T-cell proliferative responses.
      However, enriched PB CD45RA+ T cells from rheumatoid patients proliferated less
      vigorously to CD5 and CD28 ligation when compared to normal enriched CD45RA+ T
      cells. Synovial fluid (SF) T cells, which are mainly of the memory cell type, did
      not proliferate after simultaneous ligation of CD5 and CD28. This refractory
      state of synovial T cells could not be explained by a difference in the surface
      expression of CD5 or CD28. Our data suggest that the cellular immune dysfunction
      in the PB from rheumatoid patients may be due to a decreased responsiveness of
      the naive T-cell subset to accessory signals provided by CD5 and CD28. In
      addition, SF T cells appear hyporesponsive to stimulating signals provided
      through CD5 and CD28.

PMID- 7503952
TI  - Rapid modulation of renal and adrenal responsiveness to angiotensin II.
AB  - Reciprocal changes in adrenal and vascular responsiveness to angiotensin II (Ang
      II) are part of the normal adaptation to shifts in salt intake. When dietary salt
      intake is abruptly reduced from high to low, enhancement in aldosterone secretion
      requires several days to develop. Once established it is not known how quickly
      the enhancement is reversed with salt repletion. We investigated the time course
      and relative contributions of salt, volume expansion, or both to this process by
      studying 15 normotensive subjects; 5 were studied during both high-salt and low
      salt balance, and 10 were studied only in low-salt balance. For rapid volume
      expansion to reverse low-salt balance, 5 subjects received in random order an
      infusion of normal saline or dextran. The adrenal glomerulosa and renal vascular
      responses to Ang II were assessed after each volume expansion maneuver. Saline
      and dextran infusions suppressed plasma renin activity and aldosterone equally,
      although dextran acted more slowly. Both also increased renal perfusion and renal
      vascular and pressor responses to Ang II, which in 3 to 7 hours became identical
      to responses seen during high-salt intake ("modulation"). Saline infusion also
      blunted adrenal responsiveness to Ang II during that same interval. Despite
      suppression of the renin-angiotensin system by dextran infusion, aldosterone
      responsiveness to Ang II remained enhanced. These observations suggest that the
      renal and vascular responses to Ang II are modulated rapidly by the effects of
      volume expansion per se.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503953
TI  - Transcellular retrograde labeling of radial glial cells with WGA-HRP and DiI in
      neonatal rat and hamster.
AB  - Topographically distinct populations of radial glial cells in the diencephalon
      and mesencephalon of neonatal rats and hamsters were transcellularly labeled with
      wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and with the
      lipophilic tracer DiI. A comparison of the histological distribution of the two
      tracers is suggestive of two different mechanisms of transcellular labeling.
      Intraocular injections of WGA-HRP resulted in the uptake of exogenously applied
      WGA-HRP by retinal ganglion cells, followed by anterograde axonal transport and
      exocytosis within the optic target nuclei. In addition to the transneuronal
      labeling, which is typical of such injections, we observed the transcellular
      labeling of the processes and somata of radial glial cells that were
      topographically associated with the terminal fields of the labeled axons. Similar
      transcellular labeling of radial glial cells associated with the axon terminal
      fields of the colliculogeniculate projection to the medial geniculate nucleus was
      observed following injections of WGA-HRP in the inferior colliculus. The
      transcellular labeling within the radial glial cells was discontinuous and
      somatopetally concentrated, indicating the existence of a retrograde active
      transport mechanism within the radial glial processes subsequent to its uptake
      following release of tracer from axons. This type of labeling can be referred to
      as transcellular retrograde glioplasmic transport. In contrast, DiI was used as a
      tracer through its capacity to diffuse within the plasmalemma. Topographically
      distinct populations of radial glial cells were transcellularly labeled following
      placements of DiI in the retina, inferior colliculus, or dorsal thalamus of fixed
      brains. The radial processes of labeled radial glial cells consistently extended
      into regions that also contained labeled axons. It is likely that the
      transcellular radial glial labeling with DiI occurred via transmembranous
      diffusion. These data indicate that a close structural and functional relation
      exists between axons and glial cells in the developing brain.

PMID- 7503954
TI  - Oligodendrocyte development and differentiation in the rumpshaker mutation.
AB  - The jimpy rumpshaker (jprsh) mutation is an amino acid substitution in exon 4
      (Ile186-->Thr) of the proteolipid protein (PLP) gene on the X chromosome.
      Affected mice show moderate hypomyelination of the central nervous system (CNS)
      with increased numbers of oligodendrocytes in the white matter of the spinal
      cord, a feature distinguishing them from other PLP mutations such as jp, in which
      premature cell death occurs with reduced numbers of oligodendrocytes. Myelin
      sheaths of jprsh immunostain for myelin basic protein (MBP) and DM-20, but very
      few contain PLP. This study examines the differentiation of oligodendrocytes
      cultured from the spinal cords of young mutant and wild type mice using various
      surface and cytoplasmic antigenic markers to define the stage of development. The
      majority of oligodendrocytes from mutant mice progress normally to express MBP;
      approximately 30%, relative to wild type, contain DM-20 at the in vivo age of 16
      days, but very few immunostain for PLP or the O10 and O11 markers. The morphology
      of mutant cells in respect to membrane sheets and processes appears similar to
      normal. The jprsh oligodendrocyte is, therefore, characterized by a failure to
      express the markers indicative of the most mature cell; however, it is probably
      able to achieve a normal period of survival. These data, taken in conjunction
      with previous results, suggest that the PLP gene has at least two functions; one,
      probably involving PLP, is concerned with a structural role in normal myelin
      compaction; the other, perhaps related to DM-20 (or another lower molecular
      weight proteolipid), is essential for cell survival. The mutation in jprsh at
      residue 186 suggests that this region, which is common to PLP and DM-20, is not
      critical for this latter function.

PMID- 7503955
TI  - CT scan in blunt abdominal trauma.
AB  - CT scan has been used in blunt abdominal trauma with increasing popularity during
      the last decade. The sensitivity, specificity and accuracy of CT scan in blunt
      abdominal trauma have been reported to be very high. CT scan has been shown to
      eliminate the disadvantages of diagnostic peritoneal lavage (DPL) in the
      diagnosis of retroperitoneal organ injuries and when there are associated major
      pelvic fractures. This study describes the results of CT scan in 50 blunt
      abdominal trauma patients at the Chulalongkorn Hospital, Bangkok, Thailand. All
      patients had stable vital signs at the time of CT scanning although 36 per cent
      were in shock on arrival. In all, 34 per cent had associated pelvic fractures.
      Retroperitoneal organ injuries were suspected in 80 per cent. Of the patients, 34
      per cent underwent exploratory laparotomies because of positive CT scan with
      three unnecessary operations. The sensitivity of CT scan to predict the necessity
      of operation is 100 per cent, specificity 92 per cent, accuracy 94 per cent,
      positive predictive value 82 per cent and negative predictive value 100 per cent.
      We conclude that CT scan is highly reliable in the management of blunt abdominal
      trauma, especially when retroperitoneal organ injuries are suspected or when
      there are associated major pelvic fractures. CT scan is also an invaluable tool
      in selected cases of non-operative management of hepatic trauma.

PMID- 7503956
TI  - Characterization of a monoclonal antibody against human prolactin receptors.
AB  - Tamoxifen is the first line of therapy for most human breast cancers. It not only
      works through the estrogen receptor but also can directly affect the binding of
      prolactin to its receptor. To define this latter mechanism, the nature of the
      prolactin receptor needs to be clearly defined. Monoclonal antibody (MAb) B6.2,
      and IgG1 raised against a membrane-enriched fraction from metastatic human breast
      cancer cells, was as effective as polyclonal anti-prolactin receptor antibody in
      inhibiting the binding of prolactin to membranes from human tissue and to T47D
      human breast cancer cells. Control MAbs, MOPC-2I and the anti-NCA B1.1 MAb, had
      no effect on binding. Epidermal growth-factor receptors on these same cells were
      unaffected by B6.2. Prolactin-induced growth of the T47D cells was blocked by
      addition of B6.2 to the media while the control antibodies were without effect.
      Specific binding of B6.2 to the cells was completely inhibited by prolactin.
      Binding of both prolactin and B6.2 was inhibited by growing the T47D cells in the
      presence of tunicamycin A1 under conditions where protein synthesis was not
      affected but glycosylation of proteins was. An affinity column of B6.2 was used
      to purify its antigen from T47D cells. The primary purification product, a M(r)
      90,000 protein, specifically bound the lactogenic hormones human prolactin, human
      growth hormone and ovine prolactin but not the somatogenic hormone, bovine growth
      hormone and was precipitated by the polyclonal anti-prolactin receptor antibody
      but not by control MAbs. When tryptic and V8 digests of the B6.2 antigen and
      purified prolactin receptors were compared, identical electrophoretic profiles
      were obtained. Mouse 3T3 cells, when stably transfected with the gene for the
      long form of the human prolactin receptor, reacted with B6.2 and polyclonal anti
      prolactin receptor antibody. Parental 3T3 cells, devoid of prolactin receptors,
      were negative for all antibodies tested. Thus, MAb B6.2 provides a useful tool
      for further studies on purification and characterization of these receptors from
      human tissues and may provide new insights into treatment for breast cancer.

PMID- 7503957
TI  - Non-viral risk factors for nasopharyngeal carcinoma in the Philippines: results
      from a case-control study.
AB  - In a case-control study of NPC conducted in the Philippines, 104 predominantly
      non-Chinese (< 10% ethnically Chinese) cases of nasopharyngeal carcinoma (NPC)
      and 205 hospital and community controls were recruited. Risk factor information
      was obtained through personal interview. The occupational history of each subject
      was reviewed "blind" by an industrial hygienist to determine estimates of
      exposure to formaldehyde, solvents, dusts, exhaust and pesticides. After control
      for confounding, subjects who were first exposed to formaldehyde 25 or more years
      prior to diagnosis/interview or wo were first exposed before the age of 25 were
      found, in relation to those never exposed, to be at a 4.0-fold excess risk of
      disease. Similarly, those first exposed to dust and/or exhaust 35 or more years
      prior to diagnosis/interview were at a 4.4-fold excess risk of disease and those
      first exposed before the age of 20 were at a 3.5-fold excess risk of disease.
      Salted fish consumption was not associated with risk, while consumption of
      processed meats protected against NPC. Smoking was positively associated with
      NPC, but only when cases were compared to community controls. Relative to non
      smokers, subjects reporting more than 30 years of smoking were at an adjusted 7.2
      fold excess risk of disease. Herbal medicine use and burning of anti-mosquito
      coils were both independently associated with risk of NPC, with ever-users of
      herbal medicines being at a 2.5-fold excess risk of disease and those reporting
      daily use of anti-mosquito coils being at a 5.9-fold excess risk of disease
      relative to never users. Exposure to solvents, pesticides, or use of betel nuts
      were not associated with NPC risk.

PMID- 7503958
TI  - Immune recognition of human colonic-tumour-associated MUC-2 mucins using an anti
      peptide antibody.
AB  - In human intestinal malignancy, alterations occur in the expression of mucins
      defined by the MUC-2 gene. These changes include the unmasking of epitopes in the
      mucin protein core. In order to probe these modifications associated with mucins
      of the malignant phenotype, a monoclonal antibody (MAb) was developed against
      synthetic peptide with a sequence based upon that of the protein core of the MUC
      2 mucin. The antibody (designated 996) was shown to recognize a high-molecular
      weight glycoprotein from colonic carcinoma tissue. The material reacted uniformly
      with Concanavalin A but variably with other lectins, indicating heterogeneity in
      the associated oligosaccharide side chains. The protein core was accessible both
      to 996 antibody binding and to degradation with proteases. Immunization with the
      affinity-purified mucin-like material elicited antibodies reactive with both the
      immunogen and the synthetic peptides, confirming the immunogenic character of
      protein-core determinants. Epitope mapping studies, using synthetic peptides in
      solution and synthetic peptides tethered to the heads of plastic pins, indicated
      that the minimum epitope for the 996 antibody is a tetramer of T G T Q. Antibody
      interaction with the glutamine (Q) residue was determined to be of major
      importance in the antigen-antibody reaction. The findings illustrate the
      characterization of an anti-peptide antibody which may be used to probe
      alterations in MUC-2 mucin expression associated with human intestinal malignant
      disease.

PMID- 7503959
TI  - Detection of circulating intercellular adhesion molecule-1 in hepatocellular
      carcinoma.
AB  - Serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) were
      measured in 23 patients with chronic hepatitis (CH), 22 with liver cirrhosis (LC)
      and 45 with hepatocellular carcinoma (HCC) using an ELISA. Serum samples from all
      patients showed significantly higher cICAM-1 levels than serum from 50 normal
      controls. The cICAM-1 level was significantly increased in LC or HCC when
      compared with CH, but no differences were noted between LC and HCC. Levels of
      cICAM-1 correlated well with serum bilirubin, retention rate of indocyanine
      green, hyaluronic acid, type IV collagen 7-S and type III procollagen peptide
      levels but not with tumor size or circulating tumor markers (alpha-fetoprotein
      and des-gamma-carboxyprothrombin). Our findings indicate that the measurement of
      cICAM-1 is useful for the determination of the severity of liver disease and
      hepatic fibrosis. HCC tissues obtained from 10 patients were
      immunohistochemically stained for ICAM-1. Enhanced ICAM-1 expression was found on
      the tumor cell membranes. Sequential measurements of cICAM-1 levels showed that
      they changed in a similar manner to those of alpha-fetoprotein during the course
      of treatment of HCC in a patient with very high pretreatment levels of both
      markers. These results suggest that HCC cells shed ICAM-1 into the circulation.
      We conclude that cICAM-1 is not a diagnostic marker for HCC, but may be useful
      for monitoring the response to treatment.

PMID- 7503960
TI  - Enhanced expression of LFA-3 on human T-cell lines and leukemic cells carrying
      human T-cell-leukemia virus type 1.
AB  - Previously, we studied the surface expression of LFA-1 (CD11a/CD18) and ICAM-1
      (CD54) in a panel of 16 human T-cell lines and found that those carrying HTLV-1
      pro-viruses expressed high levels of ICAM-1. Enhanced expression of ICAM-1 was
      also seen in fresh leukemic cells from ATL patients. In the present study, we
      systematically examined the surface expression of 19 different cell-adhesion
      molecules (CAMs) (the immunoglobulin superfamily, the homing receptors, the
      integrins, etc.) in a panel of 20 human T-cell lines (6 HTLV-1-negative lines and
      14HTLV-1-positive lines). The surface expression of LFA-3 (CD58) was constantly
      enhanced in HTLV-1-positive T-cell lines except for MT-1, an ATL-derived cell
      line, which was devoid of a number of CAMs including ICAM-1. LFA-3 proteins and
      mRNA were found at strongly increased levels in HTLV-1-positive T-cell lines.

PMID- 7503961
TI  - Gamma-globulin modulates growth of EBV-derived B-cell tumors in SCID mice
      reconstituted with human lymphocytes.
AB  - The effect of weekly gamma-globulin injection on the development of human B-cell
      tumors was studied in 120 mice with severe combined immunodeficiency (SCID). The
      mice were injected intraperitoneally (i.p.) with human peripheral mononuclear
      cells (PBMC) from 6 different Epstein-Barr virus (EBV)-seropositive donors.
      Animals repopulated with cells from 5 donors received gamma-globulin or saline
      for 20 weeks and were followed up to 24 weeks after reconstitution. A delay in
      the appearance of fata EBV-derived human B-cell tumors was noticed in the gamma
      globulin-treated groups as compared to the controls. In a separate experiment,
      the effect of gamma-globulin treatment during the initial 4 weeks after
      reconstitution was compared to treatment from week 5 to week 8 as well as to a
      continuous 20-week treatment. The results from this experiment showed that B-cell
      tumor growth could be prevented just as efficiently when the animals were treated
      only during the first 4 weeks. In contrast, no preventive effect was seen when
      the first gamma-globulin dose was given at the beginning of week 5 after
      reconstitution. Our results indicate that gamma-globulin reduces the frequency of
      EBV-derived B-cell tumor development and suggest that SCID mice repopulated with
      human cells represent a useful in vivo model for evaluation of the prophylactic
      and/or therapeutic effects of immunomodulatory treatments in lympho-proliferative
      disorders associated with immunosuppression.

PMID- 7503962
TI  - alpha GalNAc is essential for recognition of Exo-1 epithelial antigen by mouse
      monoclonal antibody Pa-G-14.
AB  - Mouse monoclonal antibody Pa-G-14 detects Exo-1, an antigen whose expression is
      regulated in the processes of epithelial-cell differentiation and transformation.
      The epitope recognized by Pa-G-14 is present both in glycosphingolipids and in
      mucin glycoproteins. To characterize the specificity of Pa-G-14, immuno-thin
      layer chromatography, biochemical, and enzymatic treatment of glycosphingolipid
      extracts from human pancreas were used. The antibody bound to all blood-group-A
      substances; alpha GalNAc, but not fucose, was essential for reactivity. In ELISA,
      Pa-G-14 also reacted with ovine and bovine submaxillary mucins but not with
      porcine submaxillary mucin. Binding to ovine submaxillary mucin was resistant to
      neuraminidase treatment. In solid-phase absorption assays on synthetic
      carbohydrate structures, Pa-G-14 recognized broadly blood group A, Tn and sialyl
      Tn. Using immuno-electron-microscopic techniques, reactivity with all Golgi
      cisternae and mucin droplets of mucous cells in ovine submaxillary gland was
      demonstrated. All these assays indicate that Pa-G-14 shows a novel specificity,
      since it binds blood group A, Tn and sialyl-Tn, the common structural feature of
      these epitopes being the presence of a terminal alpha GalNAc sugar unit.

PMID- 7503963
TI  - Systematic study of substance P analogs. I. Evaluation of peptides synthesized by
      the multipin method for quantitative receptor binding assay.
AB  - The multipin peptide synthesis technique, a method for simultaneous multiple
      peptide synthesis, was developed for large-scale screening of oligopeptides
      [Geysen et al. (1984) Proc. Natl. Acad. Sci. USA, 81, 3998-4002]. A modification
      of the technique allows the peptides assembled on polyethylene pins to be cleaved
      in their native amide form and reconstituted into physiologically compatible
      solutions. In this study, the suitability of these peptides for quantitative
      receptor binding assay was evaluated. Substance P and 18 analogs, including a set
      of N-terminal truncated substance P and a set of naturally occurring substance P
      analogs, were synthesized by the multipin methods. An average yield of 20 +/- 3
      nmol of peptide per pin was obtained. The purity of the peptides was estimated to
      be ca. 90%. The binding activities of these peptides were determined in a
      competition assay against 125I-BHSP binding to a rat brain synaptosome
      preparation. The rank order of the affinities of these peptides depicted a
      typical pharmacological profile of central NK1 receptor. The IC50 values obtained
      were also in good agreement with data reported by other groups using similar
      experimental conditions, except that bulk synthesized peptides were used. This
      study demonstrates that the peptides synthesized with the multipin technique are
      suitable for quantitative receptor studies, particularly for a high-volume
      screening of bioactive peptides.

PMID- 7503965
TI  - Some diagnostic and therapeutic issues in HIV infection.

PMID- 7503964
TI  - Systematic study of substance P analogs. II. Rapid screening of 512 substance P
      stereoisomers for binding to NK1 receptor.
AB  - Recent developments in multiple peptide synthesis have made it feasible to
      synthesize and screen large numbers of peptide analogs simultaneously. We report
      here a model study of large scale screening of stereoisomers of substance P with
      systematic D-amino acid replacements. Such studies are useful in exploring
      conformational requirements of peptide-receptor interaction and to provide
      empirical information for peptide drug design. 512 stereoisomers of SP were
      prepared by the multipin peptide synthesis method. Receptor binding affinities of
      these analogs were estimated by an iterative competition assay. Results obtained
      form a comprehensive database on the stereochemical requirement of SP binding to
      central NK1 receptor. Data from analogs with single D-amino acid replacement are
      consistent with those previously reported showing that SP binding is highly
      sensitive to the chirality change of the C-terminal residues (Gln6-Leu10), but
      less sensitive to the chirality change of the N-terminal residues (Arg1-Gln5). A
      qualitative analysis of the database by comparison of series of peptide pairs
      revealed a repeated pattern of affinity change with D-amino acid replacement,
      suggesting a largely additive binding activity of SP from each residue. On the
      other hand, possible intramolecular interactions between some N-terminal and C
      terminal residues to form an optimal binding conformation were also found. A set
      of 189 peptides with IC50 values less than 5 microM was subjected to an empirical
      QSAR analysis using a linear additive model. The relative contribution
      coefficients obtained agreed with the observation that the predominant
      contribution comes from the C-terminal residues, suggesting considerable
      independency of each residue on binding to NK1 receptors.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7503966
TI  - Update on reverse transcriptase inhibitors in HIV disease.

PMID- 7503967
TI  - An encounter with homeless mothers and children: gaining an awareness.
AB  - This article describes the experience of two nurses who established and conducted
      concurrent support groups for homeless mothers and their preschool children. The
      group sessions were 75 minutes in length and occurred once a week for 10 weeks.
      Both mothers and children were depressed and felt hopeless. Mothers manifested
      signs of grief and made statements indicative of severely eroded self-concepts.
      This resulted in a diminished ability to provide for the basic needs of their
      children. Most of the children demonstrated social, motor, and language skills
      far below the levels appropriate for their ages. Poor health was a consistent
      finding, especially among the children. An incentive program used to promote
      attendance in parent's group is described. Other successful and unsuccessful
      interventions are reviewed and specific recommendations for successful
      intervention with homeless families are provided.

PMID- 7503968
TI  - Universal screening better for children.

PMID- 7503970
TI  - Histochemical and biochemical determination of calcium in salivary glands of cat.
AB  - Although feline salivary glands have been used in investigations on secretion and
      microlithiasis and both processes involved calcium, nothing is known about its
      distribution in these glands. Therefore we have demonstrated the presence of
      calcium by a histochemical technique using glyoxal bis(2-hydroxyanil) and a
      biochemical technique using dry ashing. The histochemical technique stained
      serous acinar cells weakly and rarely found mucous acinar cells strongly in the
      parotid gland, mucous acinar cells moderately to strongly and serous acinar cells
      weakly in the sublingual gland, and central and demilunar acinar cells moderately
      to strongly in the submandibular gland. The biochemical technique revealed less
      calcium in the parotid than in the submandibular and sublingual glands. Both
      techniques revealed a decrease of calcium in submandibular and sublingual glands
      following parasympathetic stimulation. The histochemical distribution of calcium,
      which corresponds to that of acinar secretory glycoprotein, and the loss of
      calcium following parasympathetic stimulation, which causes release of secretory
      granules, indicate the presence of calcium in secretory granules. The
      concentration of calcium in the different types of acinar cell corresponds to the
      acidity of the secretory glycoprotein and suggests that calcium is present as a
      cationic shield to allow the condensation of polyionic glycoprotein in secretory
      granules.

PMID- 7503969
TI  - Monoclonal antibodies that recognize the trisaccharide epitope Gal alpha 1-3Gal
      beta 1-4GlcNAc present on Ehrlich tumor cell membrane glycoproteins.
AB  - Monoclonal antibodies were prepared against the trisaccharide Gal alpha 1-3Gal
      beta 1-4GlcNAc, a sequence which occurs on the surface of Ehrlich ascites tumor
      cells as well as in thyroglobulin, laminin and a variety of other proteins. This
      was accomplished by immunizing BALB/c mice with the fraction of Ehrlich cell
      membrane glycoproteins obtained by affinity chromatography on a Griffonia
      simplicifolia I (GS I) column which selectively binds alpha-D-galactosyl
      terminated structures. Detection of Gal alpha 1-3Gal beta 1-4GlcNAc-specific
      antibodies was accomplished by employing glycoproteins containing the
      trisaccharide sequence; fusion with spleen cells from an immunized mouse was
      accomplished in the presence of polyethylene glycol (PEG1500). An enzyme-linked
      immunosorbent assay (ELISA) system was used to identify two clones (2.10G and
      6.8E), which recognized the desired trisaccharide conjugate. These clones also
      recognized a thyroglobulin fraction isolated by GS I affinity chromatography and
      murine laminin, both of which possess the Gal alpha 1-3Gal beta 1-4GlcNAc
      sequence. Inhibition of antibody-trisaccharide reactivity, examined employing an
      ELISA assay, revealed that two trisaccharides, Gal alpha 1-3Gal beta 1
      4GlcNAc/Glc, were the best inhibitory haptens; Gal beta 1-4GlcNAc (LacNAc), Gal
      alpha 1-3Gal and Gal beta 1-4Glc (lactose) were poor inhibitors. Indirect
      immunofluorescence staining of unfixed Ehrlich cells using the monoclonal
      antibody at 4 degrees C revealed fluorescence over the entire cell surface.
      Indirect immunogold labeling of semithin and ultrathin sections of aldehyde fixed
      and Lowicryl K4M-embedded Ehrlich cells resulted in specific labeling of the cell
      surface and internal structure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7503972
TI  - Epitope fine specificity of human anti-HLA-A2 antibodies. Identification of four
      epitopes including a haptenlike epitope on HLA-A2 at lysine 127.
AB  - Anti-HLA-A2 CREG antibodies were purified from seven individuals by affinity
      chromatography. The binding of the purified antibodies to single or multiple
      amino acid variants of HLA-A2.1 was measured with an inhibition RIA.
      Substitutions at 10 amino acid residues in the polymorphic alpha 1 and alpha 2
      domains were important for human antibody binding; eight of these have previously
      been shown to be important in the binding of murine anti-HLA-A2 CREG antibodies.
      Unlike any previously reported murine mAbs, the binding of antibodies from two
      individuals was eliminated by a substitution at the HLA-A2, -24, -28 shared loop
      amino acid residue lysine 127. Conversely, when the asparagine at residue 127 on
      the non-cross-reactive HLA-A3 was replaced with lysine, antibody binding was
      completely restored. The results further suggest that both lambda- and kappa
      containing human antibodies that bind to this region may recognize lysine 127 as
      a haptenlike epitope. Anti-HLA-A2 antibodies that recognized a conformational
      epitope defined by changes at glycine 62 in the alpha 1 domain were predominated
      by lambda light chains whereas those that recognize an epitope defined by a loop
      residue at tryptophan 107 in the alpha 2 domain were predominated by kappa light
      chains. The data are consistent with a model of restricted epitope recognition of
      HLA-A2 by human B cells that is similar to, but distinct from, epitope
      recognition by mouse B-cell hybridomas, and may help to explain the phenomenon of
      public or cross-reactive idiotypes in the HLA system.

PMID- 7503971
TI  - Robert Feulgen Lecture 1993. L-selectin and its biological ligands.
AB  - This review considers the leukocyte adhesive receptor known as L-selectin. This
      protein, belonging to the selectin family of cell-cell adhesion receptors,
      mediates adhesion by virtue of a C-type lectin domain at its amino terminus. The
      protein was discovered as a lymphocyte homing receptor involved in the attachment
      of lymphocytes to high endothelial venules (HEV) of lymph nodes. Its widespread
      distribution on all leukocyte populations underlies a more general role in a
      variety of leukocyte-endothelial interactions. In the HEV interaction, cognate
      HEV ligands for L-selectin have been identified as two sulfated, sialylated, and
      fucosylated glycoproteins, known as GlyCAM-1 and Sgp90. These ligands have mucin
      like domains which confer important properties for their proposed adhesive
      function. The carbohydrate features of these ligands, essential for their
      interaction with L-selectin, are reviewed. The existence of extralymphoid ligands
      for L-selectin is also discussed.

PMID- 7503973
TI  - Neoadjuvant chemotherapy and radiotherapy in locally advanced esophagus
      carcinoma: long-term results.
AB  - PURPOSE: A prospective study with neoadjuvant chemotherapy and radiotherapy in
      patients with locally advanced esophagus carcinoma for evaluating: toxicity,
      response rate, pattern of recurrence, and survival after a long follow-up.
      METHODS AND MATERIALS: Between 1983-1988, 40 patients with locally advanced
      squamous cell carcinoma of the thoracic esophagus were entered into a prospective
      trial of neoadjuvant chemotherapy and radiotherapy. Eight patients (20%) were
      Stage II and 32 patients (80%) were Stage III, according to American Joint
      Committee staging criteria. Neoadjuvant chemotherapy consisted of two cycles with
      cisplatin (120 mg/m2 day 1), vindesine (3 mg/m2 days 1, 8, 15, and 22) and
      bleomycin (10 mg/m2 days 3 to 6). Second cycle was initiated on day 29. Radiation
      therapy was administered 2-4 weeks after completion of chemotherapy, with a total
      dose on tumor of 60 Gy. RESULTS: Two patients died from treatment-related
      toxicity. Complete response was observed in 20 patients (53%) and symptomatic
      improvement in 31 patients (82%). The median survival was 11 months, with an
      actuarial survival at 1 year of 45%, 3 year 20%, and 5 years 15%. Significantly
      (p < 0.05) longer survival was observed in patients with Stage II (median
      survival 18 months) vs. Stage III (median survival 10 months). The pattern of
      failure was predominantly local/regional (62%). CONCLUSION: This treatment scheme
      is an effective and tolerable regimen but long-term survival was poor.

PMID- 7503974
TI  - Screening method for colony-stimulating factor inducers using a human bone marrow
      stromal cell line, KM-102.
AB  - A new screening method for inducers of colony-stimulating factors (CSFs) was
      established using KM-102, a human bone marrow stromal cell line as the producer.
      In this method, the assay system which uses CSF dependent cell lines is combined
      with the CSF production system. Interleukin-1 (IL-1), which is known to
      upregulate CSF production in many cell populations, was used as a positive
      control for production of granulocyte CSF (G-CSF) and granulocyte-macrophage CSF
      (GM-CSF). Induction in the positive controls was clearly detected within 24
      hours. Activators of protein kinase C (PKC), protein phosphatase inhibitors and
      lipopolysaccharide (LPS) were positive in this assay system, but muramyl
      dipeptide (MDP) and Bestatin which are known macrophage activators, were
      negative. Inducers of CSFs were successfully detected using this assay method.
      Among 1,600 microbial strains tested, 2 actinomycete strains were found to
      produce active substances. One strain produces teleocidin-A, a strong activator
      of PKC, and the other strain produces a mixture of active compounds including
      three novel compounds. These three compounds do not induce terminal
      differentiation of HL-60 cells, suggesting that they are not teleocidin-like
      substances and form a new class of CSF inducers.

PMID- 7503975
TI  - Novel microbial metabolites of the phoslactomycins family induce production of
      colony-stimulating factors by bone marrow stromal cells. I. Taxonomy,
      fermentation and biological properties.
AB  - Three metabolites were isolated from the culture broth of an actinomycete strain
      identified as Streptomyces platensis SANK 60191, that induce the production of
      colony-stimulating factors (CSFs) by stromal cell line KM-102 at ED50
      concentrations from 40 to 200 ng/ml. The compounds induced quantities of
      granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) comparable to
      those induced by interleukin-1, a strong CSF inducer. These metabolites were
      called leustroducsins (A, B and C) and were later found to be structurally
      related to phoslactomycins. This is the first report of CSF inducing activity by
      members of the phoslactomycin class.

PMID- 7503976
TI  - Novel microbial metabolites of the phoslactomycins family induce production of
      colony-stimulating factors by bone marrow stromal cells. II. Isolation, physico
      chemical properties and structure determination.
AB  - Leustroducsins (LSNs) A, B and C, novel inducers of colony-stimulating factors
      (CSFs), were isolated from culture broth of Streptomyces platensis SANK 60191
      mainly by ethyl acetate extraction and preparative reverse-phase HPLC. The
      molecular weights and molecular formulae of LSNs A, B and C are 641: C32H52O10NP,
      669: C34H56O10NP and 669: C34H56O10NP, respectively. The structure elucidation
      revealed that they belong to the phoslactomycin group antibiotics, and their
      structures contain an alpha,beta-unsaturated delta-lactone, an amino group, a
      phosphate ester and a cyclohexane ring moiety. The structures differ only at the
      substituent bound to the cyclohexane ring.

PMID- 7503977
TI  - Biological specificity of bottled natural mineral waters: characterization by
      ribosomal ribonucleic acid gene restriction patterns.
AB  - The organisms from heterotrophic plate counts of four brands of bottled non
      carbonated mineral waters were analysed by ribosomal ribonucleic acid gene
      restriction patterns in addition to identification by customary techniques. Five
      commercialized bottles of each brand were examined once in the year 1989-90. The
      total bacterial flora was divided into two main groups: the pseudomonads and the
      unidentified strains. Whereas phenotypic results did not reveal any significant
      differences between the four brands, rRNA gene restriction patterns were
      discriminatory. Among the 73 strains studied, 45 distinct patterns were observed,
      with only three common to several springs. These results reveal, at one
      determined time, a remarkable biological specificity of each brand of water.

PMID- 7503978
TI  - Modified nucleotides of tRNA(3Lys) modulate primer/template loop-loop interaction
      in the initiation complex of HIV-1 reverse transcription.
AB  - In all retroviruses, reverse transcription is primed by a tRNA whose 3' end 18
      nucleotides are complementary to the so called viral primer binding site.
      Previous work showed that reverse transcription of HIV-1 RNA is initiated by
      tRNA(3Lys). Using a variety of chemical and enzymatic structural probes, we
      investigated the interactions between HIV-1 RNA and its natural primer
      tRNA(3Lys). In addition to the predictable contacts between the viral primer
      binding site and the 3' end of tRNA(3Lys), a specific interaction takes place
      between an A-rich loop located upstream of the primer binding site region and the
      anticodon loop of tRNA(3Lys). This AAAA/Umcm5s2UUU loop-loop interaction is not
      observed when the natural primer is replaced by an in vitro synthesized
      tRNA(3Lys) transcript. Furthermore, dethiolation of the modified nucleotide
      mcm5s2U at position 34 of tRNA(3Lys) strongly destabilizes this interaction.
      Sequence and structure comparisons indicate that the primer/template loop-loop
      interaction is conserved in all HIV-1 isolates, and possibly also in HIV-2 and
      SIV.

PMID- 7503979
TI  - Cyclic AMP stimulates efflux of intracellular sterol from cholesterol-loaded
      cells.
AB  - The interaction of high density lipoprotein with its putative receptor stimulates
      translocation and efflux of intracellular sterols by a process involving
      activation of protein kinase C. This study shows that activation of cAMP
      dependent protein kinase also stimulates efflux of intracellular sterols. When
      intracellular sterol pools of cholesterol-loaded cultured human skin fibroblasts
      and bovine aortic endothelial cells were radiolabeled with the biosynthetic
      precursor [3H]mevalonolactone, high density lipoprotein3 (HDL3)-mediated 3H
      sterol efflux was enhanced by addition of the adenylylcyclase activator
      forskolin, the phosphodiesterase inhibitors theophylline and 3-isobutyl-1
      methylxanthine, and the cAMP analogues N6-benzoyl-cAMP (N6-cAMP) and 8-thiomethyl
      cAMP. The effect of N6-cAMP was abolished by an inhibitor of cAMP-dependent
      protein kinase (H8). The enhanced sterol efflux was independent of receptor
      binding of HDL3, as similar effects were observed in the presence of
      tetranitromethane-modified HDL3, which lacks receptor binding activity. N6-cAMP
      stimulated efflux of several subspecies of newly synthesized sterols, including
      cholesterol. Elevation of cAMP levels increased the proportion of radiosterols
      that were accessible to treatment of cells with the enzyme cholesterol oxidase,
      suggesting that activation of cAMP-dependent protein kinase stimulates
      translocation of sterols from intracellular compartments to the plasma membrane
      where they desorb from the cell surface. Thus, at least two distinct protein
      kinase signalling pathways modulate transport of intracellular sterols in
      cholesterol-loaded cells.

PMID- 7503980
TI  - Rapamycin-FKBP12 blocks proliferation, induces differentiation, and inhibits cdc2
      kinase activity in a myogenic cell line.
AB  - Rapamycin is a potent immunosuppressant that binds to the cytosolic protein,
      FKBP12, and blocks T cell activation. Here we report that rapamycin also blocks
      myogenic proliferation and induces differentiation, associated with a decrease in
      p34cdc2 activity and cyclin A levels. In yeast and mammals, rapamycin blocks cell
      cycle progression by causing G1 arrest, arguing for a conserved signaling pathway
      governing the G1 to S transition. p34cdc2 has been shown to play a role in both
      the transition from G1 to S and from G2 to M in yeast. In higher eukaryotes the
      role of p34cdc2 in G1 to S transition is less clear. Rapamycin and the
      structurally related macrolide antibiotic FK506 both bind to a cytosolic protein,
      the FK506-binding protein (FKBP12). We show that inhibition of myogenic
      proliferation is achieved at low doses of rapamycin (< 1 ng/ml) and is competed
      by a molar excess of FK506, indicating specificity for FKBP12. The distinct FK506
      calcineurin pathway did not affect myogenic proliferation, differentiation, or
      p34cdc2 kinase activity. Thus, the rapamycin-FKBP12 signaling pathway involves a
      specific and direct effect on p34cdc2 kinase activity at the G1 to S transition
      and identifies a regulatory step during myogenic differentiation.

PMID- 7503981
TI  - RNA polymerase II transcription factor SIII. II. Functional properties and role
      in RNA chain elongation.
AB  - A novel transcription factor that stimulates synthesis of accurately initiated
      transcripts by mammalian RNA polymerase II has been identified and purified to
      apparent homogeneity from rat liver extracts (Bradsher, J. N., Jackson, K. W.,
      Conaway, R. C., Conaway, J. W. (1993) J. Biol. Chem. 268, 25587-25593). This
      factor, which we designate SIII, has a native molecular mass of approximately 140
      kDa and is composed of three polypeptides of 110, 18, and 15 kDa. In this report,
      we demonstrate that SIII stimulates promoter-specific transcription by increasing
      the overall rate of RNA chain elongation by RNA polymerase II. Results of pulse
      chase experiments indicate that SIII does not need to be present during
      preinitiation complex formation or transcription initiation in order to stimulate
      promoter-specific transcription. In addition, SIII is able to stimulate the rate
      of RNA chain elongation by RNA polymerase II during transcription of double
      stranded oligo(dC)-tailed templates. Taken together, these findings indicate that
      the factor exerts its activity directly on the elongation complex.

PMID- 7503983
TI  - Retinoic acid posttranscriptionally up-regulates proteolipid protein gene
      expression in C6 glioma cells.
AB  - The proteolipid protein (PLP) gene codes for the major central nervous system
      myelin protein. We have studied the effects of different agents on the expression
      of the PLP gene in C6 glioma cells. Retinoic acid (RA), but not dexamethasone,
      estradiol, insulin, growth hormone, or vitamin D3, had a drastic effect,
      increasing 10-20-fold the level of PLP mRNA. Concomitantly, RA also induced the
      appearance of the corresponding immunoreactive protein. The increase in PLP RNA
      level showed a slow kinetics and was blocked by cycloheximide, suggesting a
      posttranscriptional regulation by RA. Nuclear run-on assays confirmed that the
      rate of PLP gene transcription was unchanged by RA. In contrast, we found that
      retinoic acid augmented PLP mRNA stability, causing a substantial increase in its
      half-life. RA action was independent of cell density, serum, or PDGF but was
      partially inhibited by bFGF. On the other hand, thyroid hormone caused a moderate
      increase in PLP mRNA levels in C6 cells but only when the low numbers of thyroid
      receptors in these cells were increased by retrovirally mediated expression of an
      exogenous c-erbA/TR alpha-1 gene. Our results indicate that RA specifically up
      regulates PLP expression in glioma C6 cells at a posttranscriptional level by
      increasing PLP RNA half-life.

PMID- 7503982
TI  - Nascent RNA cleavage by arrested RNA polymerase II does not require upstream
      translocation of the elongation complex on DNA.
AB  - Obstacles incurred by RNA polymerase II during primary transcript synthesis have
      been identified in vivo and in vitro. Transcription past these impediments
      requires SII, an RNA polymerase II-binding protein. SII also activates a nuclease
      in arrested elongation complexes and this nascent RNA shortening precedes
      transcriptional readthrough. Here we show that in the presence of SII and
      nucleotides, transcript cleavage is detected during SII-dependent elongation but
      not during SII-independent transcription. Thus, under typical transcription
      conditions, SII is necessary but insufficient to activate RNA cleavage. RNA
      cleavage could serve to move RNA polymerase II away from the transcriptional
      impediment and/or permit RNA polymerase II multiple attempts at RNA elongation.
      By mapping the positions of the 3'-ends of RNAs and the elongation complex on
      DNA, we demonstrate that upstream movement of RNA polymerase II is not required
      for limited RNA shortening (seven to nine nucleotides) and reactivation of an
      arrested complex. Arrested complexes become elongation competent after removal of
      no more than nine nucleotides from the nascent RNA's 3'-end. Further cleavage of
      nascent RNA, however, does result in "backward" translocation of the enzyme. We
      also show that one round of RNA cleavage is insufficient for full readthrough at
      an arrest site, consistent with a previously suggested mechanism of SII action.

PMID- 7503984
TI  - Incorporation of the pancreatic membrane protein GP-2 into secretory granules in
      exocrine but not endocrine cells.
AB  - The pancreatic zymogen granule membrane protein GP-2 was introduced into cells of
      exocrine or endocrine origin by transfection of its cDNA in order to investigate
      the mechanisms by which proteins are specifically incorporated into the membranes
      of secretory granules. Permanent transformants expressing GP-2 were isolated from
      exocrine pancreatic-derived AR42J cells as well as AtT20 cells of anterior
      pituitary origin and insulinoma-derived Rin5F cells. In AR42J cells, GP-2 was
      localized by immunofluorescence and immunoelectron microscopy to the endogenous
      zymogen-like granules as well as to the plasma membrane. In experiments
      supporting the localization data, incubation of the AR42J transformants with the
      secretagogue cholecystokinin (CCK8) resulted in enhanced release of a shed form
      of GP-2 into the medium in parallel with amylase, suggesting that the two
      proteins were secreted from the same compartment. By contrast, when expressed in
      AtT20 cells, the protein was found by immunofluorescence microscopy on the plasma
      membrane as well as in intracellular vesicles that differed in size and location
      from the endogenous secretory vesicles. By electron microscopy, large
      (approximately 0.5 micron) multivesicular structures were observed. Single- and
      double-label immunoelectron microscopy demonstrated that these large organelles
      labeled with anti-GP-2 antibodies, whereas the smaller adrenocorticotropic
      hormone (ACTH)-containing secretory vesicles did not. In permanent transformants
      of Rin5F cells, GP-2 was also excluded from the insulin-containing granules and
      found in multivesicular bodies similar to those in the AtT20 cells and containing
      the endosomal/lysosomal marker endolyn-78. Despite the apparent accumulation of
      GP-2 in lysosome-like structures, it turned over slowly and did not undergo rapid
      endocytosis from the cell surface. We conclude that GP-2 is targeted to secretory
      granule membranes by cell type-specific mechanisms that likely involve its
      interaction with other membrane or content proteins expressed only in the
      exocrine cells.

PMID- 7503985
TI  - Tyrosine phosphorylation of Ras GTPase-activating protein stabilizes its
      association with p62 at membranes of v-Src transformed cells.
AB  - Ras GTPase-activating protein (GAP) regulates the activity of Ras proteins, which
      have key roles in signal transduction pathways downstream of oncogenic and
      receptor tyrosine kinases. Previous studies indicated that Tyr-457 of bovine GAP
      (Tyr-460 of human GAP) is the major site of phosphorylation by viral Src (v-Src)
      kinase and epidermal growth factor receptor. The finding that Tyr-457 in GAP is
      located immediately adjacent to Src homology 2 (SH2) and 3 (SH3) domains led us
      to investigate the possibility that this specific phosphorylation regulates
      protein-protein interactions involving GAP. For this purpose, we constructed a
      full-length GAP mutant containing a substitution of Phe-457 in place of Tyr-457.
      Both wild-type GAP and mutant GAPF457 were tagged with the KT3 epitope at the
      carboxyl terminus and were expressed in v-Src transformed rat fibroblasts. In
      vivo phosphorylation analyses established that GAPF457 was weakly phosphorylated
      on tyrosine and, as expected, lacked the phosphopeptide containing Tyr-457.
      Analysis of GAP-associated proteins in anti-KT3 immunoprecipitates showed that
      GAP stably associated with two major phosphoproteins, p62 and p190, which have
      been previously described. Significantly, association of p62 with GAPF457 was
      reduced approximately 3-fold compared with wild-type GAP. Subcellular
      fractionation experiments further demonstrated that Tyr-457 phosphorylation of
      GAP stabilized its association with p62 at cell membranes. Based on these
      findings, we propose that one role of tyrosine phosphorylation in GAP is to
      enhance its association with p62 at membranes, which in turn may contribute to
      regulation of Ras signal transduction pathways.

PMID- 7503986
TI  - Effect of monoclonal antibodies specific for the 28-kDa subunit on catalytic
      properties of the calpains.
AB  - Nine monoclonal antibodies (mAbs) specific for the 28-kDa subunit common to mu-
      and m-calpains have been assayed for their effects on mu- and m-calpains. All
      nine react with the COOH-terminal part (domain VI) of the 28-kDa subunit, and all
      nine affect the Ca2+ concentration required for autolysis of m-calpain, but have
      little effect on the Ca2+ concentration required for autolysis of mu-calpain.
      None of the nine affect the specific proteolytic activity of mu- or m-calpain.
      Two of the mAbs, 5B9 and 5B3, were selected for further study. mAb 5B9 decreased
      the Ca2+ concentration required for autolysis to one-fifth of that required in
      its absence; sequencing of chymotryptic fragments showed that the epitope for mAb
      5B9 is between amino acid residues 92 and 104 of the 28-kDa subunit. mAb 5B3
      increased the Ca2+ concentration required for autolysis; the epitope for mAb 5B3
      is located between amino acid residues 148 and 178 of the 28-kDa subunit, which
      is the region that contains the first EF-hand Ca(2+)-binding sequence in this
      subunit. Although it increases the Ca2+ concentration required for autolysis, mAb
      5B3 has no effect on the Ca2+ concentration required for proteolytic activity of
      m-calpain, and unautolyzed m-calpain is not a proenzyme. That all nine mAbs react
      with domain VI and not with the NH2-terminal domain V of the 28-kDa subunit
      suggests that domain VI (and not domain V) is involved in autolysis, contrary to
      the view that phosphatidylinositol lowers the Ca2+ concentration required for
      autolysis by binding to domain V.

PMID- 7503987
TI  - Binding of the O-antigen of Shigella dysenteriae type 1 and 26 related synthetic
      fragments to a monoclonal IgM antibody.
AB  - Shigella dysenteriae type 1 possesses an O-antigen whose repeating unit is -->3)
      alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-D-Galp -(1-->3)-alpha-D- GlcpNAc
      (1-->, where Rhap is rhamnopyranosyl, Galp is galactopyranosyl, and Glcp is
      glucopyranosyl. Using ligand-induced protein fluorescence change, we have
      measured the affinities of a monoclonal murine IgM for 26 fragments of, or
      related to, the structure of the O-polysaccharide and of the IgM Fab for the
      intact O-specific bacterial polysaccharide. Synthetic saccharides used were
      methyl glycosides to ensure an anomerically defined pyranosyl ring conformation.
      The galactosyl residue is the only monosaccharide of the antigenic epitope that
      shows quantifiable binding: approximately 3.0 kcal/mol of binding free energy,
      depending on the structure and conformation of the fragment it is a part of.
      Addition of an alpha-(1-->2)-linked rhamnosyl residue increases the free energy
      of binding significantly. We propose this rhamnopyranosyl-alpha-(1-->2)
      galactopyranosyl disaccharide to be the basic determinant of the Shigella O
      polysaccharide. Further extension (by linkages as in the natural antigen) of this
      oligosaccharidic ligand toward the upstream end (in an oligo- (or poly
      )saccharide, such as A-->B-->C-->D-->E-->m, where A, B, C, D, and E are sugars
      and m is any moiety, such as methyl, we define A as the glycosyl- or upstream
      terminus, and E as the glycoside- or downstream terminus) by rhamnosyl and N
      acetylglucosaminyl moieties improves the binding only minimally. The antibody is
      quite specific for the rhamnosyl-alpha-(1-->2)-galactosyl sequence but less so
      for the nature of the attachment to the galactosyl residue on the downstream
      side. Measurements using IgM Fab and the intact O-specific polysaccharide show
      that the antibody can bind internal segments on the antigen chain. The free
      energy of binding of this antibody for the disaccharide determinant varies from 
      delta G of 4.7 to 5.1 kcal/mol, depending on its flanking residues.

PMID- 7503988
TI  - Unidirectional cross-phosphorylation between the granulocyte colony-stimulating
      factor and interleukin 3 receptors.
AB  - The mouse interleukin-3 (IL-3)-dependent hemopoietic precursor cell line 32DC13
      responds to granulocyte colony-stimulating factor (G-CSF) for proliferation and
      differentiation. We established a subline (32D-FH) of the 32DC13 cells which has
      lost the ability to respond to G-CSF. When murine G-CSF receptor cDNA was
      introduced into the 32D-FH cell line, the transformants responded to G-CSF as
      well as to IL-3 for proliferation. Adding G-CSF to the transformants rapidly
      induced tyrosine phosphorylation not only of the G-CSF receptor but also of both
      subtypes of the IL-3 receptor beta-chain (AIC2A and AIC2B molecules). On the
      other hand, stimulation of the transformants with IL-3 induced tyrosine
      phosphorylation of the AIC2A and AIC2B but not of the G-CSF receptor. These
      results indicate that the tyrosine kinase activated through the G-CSF receptor
      interacts with the IL-3 receptor beta-chains but not vice versa. This
      unidirectional cross-phosphorylation between the G-CSF and IL-3 receptors may
      play a role in granulopoiesis induced by G-CSF.

PMID- 7503989
TI  - Inhibition of histamine secretion by wortmannin through the blockade of
      phosphatidylinositol 3-kinase in RBL-2H3 cells.
AB  - The surface engagement of high affinity immunoglobulin E receptor (Fc epsilon RI)
      of rat basophilic leukemia 2H3 (RBL-2H3) cells induced histamine secretion and
      leukotriene release following activation of the tyrosine kinase Lyn together with
      phosphatidylinositol 3-kinase (PI3-kinase). Wortmannin inhibited the activity of
      partially purified PI3-kinase from calf thymus, as well as the PI3-kinase
      activity in anti-PI3-kinase p85 immunoprecipitates from RBL-2H3 cells, at a
      concentration as low as 1.0 nM and with IC50 values of 3.0 nM, but did not
      inhibit PI4-kinase activity. The inhibition of PI3-kinase by wortmannin was
      irreversible. Wortmannin inhibited both Fc epsilon RI-mediated histamine
      secretion and leukotriene release up to 80% with IC50 values of 2.0 and 3.0 nM,
      respectively. Wortmannin inhibited PI3-kinase activity in intact cells up to 80%
      with an IC50 value of 2.0 nM, which is almost equal to those for PI3-kinase in
      vitro and for histamine secretion and leukotriene release. With anti-wortmannin
      antibody, we have shown that wortmannin binds to the 110-kDa protein, but not to
      PI3-kinase 85-kDa regulatory subunit both in vitro and in whole cells.
      Furthermore, there was a positive correlation between the potencies of wortmannin
      derivatives as inhibitors of PI3-kinase and as inhibitors of histamine secretion.
      Wortmannin had no effect on the activation of the tyrosine kinase Lyn. These
      results suggest that PI3-kinase is involved in the signal transduction pathway
      responsible for histamine secretion following stimulation of Fc epsilon RI and
      that wortmannin blocks these responses through direct interaction with the
      catalytic subunit of this enzyme.

PMID- 7503990
TI  - Loss of a neutralizing epitope by a spontaneous point mutation in the V3 loop of
      HIV-1 isolated from an infected laboratory worker.
AB  - The third hypervariable region, or V3 loop, represents the principal neutralizing
      domain of the gp120 envelope glycoprotein of human immunodeficiency virus type 1
      (HIV-1). Sequential viral isolates from a laboratory worker (LW) accidentally
      infected with HIV-1IIIB in 1985 were analyzed using type-specific neutralizing
      monoclonal antibodies directed to the V3 loop. A single amino acid substitution,
      Ala-->Thr at position 21 in the V3 loop of HIV-1LW isolated in 1987, was shown to
      determine the loss of the neutralizing epitope recognized by one of the
      monoclonal antibodies (M77). However, this antibody efficiently recognized linear
      V3 loop peptides containing either the Ala or Thr residue at position 21,
      indicating that a local change in conformation was responsible for the epitope
      loss in the native gp120. Molecular modeling studies, experimentally supported by
      different amino acid replacements at position 21, indicated that the Ala-->Thr
      substitution leads to a drastic change in the domain of the V3 loop, which
      contains the complementary surface for antibody binding. These results provide
      evidence for the first time that a conformation-dependent epitope within the V3
      loop of HIV-1 is involved in the generation of neutralization escape mutants in
      vivo.

PMID- 7503991
TI  - Fe.bleomycin cleaves a transfer RNA precursor and its "transfer DNA" analog at
      the same major site.
AB  - Previously, Fe.bleomycin (BLM) has been shown to mediate RNA cleavage in a
      fashion more highly selective than that of DNA. Because RNAs often assume
      secondary and tertiary structures not commonly encountered with DNAs, it was not
      clear whether the greater selectivity of RNA cleavage was a consequence of
      differences in the mononucleotide constituents of RNA and DNA, or of the three
      dimensional structures of the individual substrates. Accordingly, we prepared a
      "tDNA" identical in sequence with Bacillus subtilis tRNA(His) precursor, the
      latter of which is known to be a good substrate for Fe(II).BLM A2 and which
      undergoes oxidative cleavage predominantly at U35. Remarkably, the tDNA underwent
      cleavage predominantly at T35. At higher concentrations of Fe(II).BLM A2, the
      tDNA was extensively degraded, while the tRNA(His) precursor was not. Competition
      experiments suggested that this was not due to more efficient binding of Fe.BLM
      to the tDNA; in fact the tRNA precursor appeared to be bound more efficiently.
      The lesser cleavage of the tRNA(His) may be due to limitations in the facility of
      chemical transformation following Fe.BLM binding, or else to the formation of RNA
      lesions that do not lead directly to RNA strand scission.

PMID- 7503992
TI  - On the role of the platelet membrane skeleton in mediating signal transduction.
      Association of GP IIb-IIIa, pp60c-src, pp62c-yes, and the p21ras GTPase
      activating protein with the membrane skeleton.
AB  - The platelet plasma membrane is lined with a membrane skeleton composed of short
      actin filaments, actin-binding protein, spectrin, vinculin, and other
      unidentified proteins. It is connected to the outside of the cell through
      association with the cytoplasmic domains of transmembrane receptors. In detergent
      lysed platelets, cytoplasmic actin filaments are sedimented by centrifugation at
      15,600 x g, but the sedimentation of membrane skeleton fragments requires higher
      g-forces (100,000 x g). In the present study, we show that the major platelet
      integrin, glycoprotein (GP) IIb-IIIa, sediments from detergent-lysed platelets at
      100,000 x g together with fragments of the membrane skeleton that contain the
      cytoskeletal proteins spectrin, vinculin, and talin. In addition, this cell
      fraction contained the tyrosine kinases pp60c-src and pp62c-yes and the p21ras
      GTPase-activating protein (GAP). After thrombin-induced platelet aggregation
      mediated by fibrinogen binding to GP IIb-IIIa on adjacent platelets, we detected
      a redistribution of spectrin, talin, vinculin, pp60c-src, and pp62c-yes to the
      fraction that sediments at 15,600 x g. The redistribution of these proteins from
      the high-speed detergent-insoluble fraction to the low-speed fraction correlated
      with the extent of aggregation and was not detected in aggregation-defective
      thrombasthenic platelets (which lack the GP IIb-IIIa complex). In addition, many
      of the proteins phosphorylated on tyrosine in activated platelets were present in
      detergent-insoluble fractions. These results are consistent with the
      possibilities that 1) GP IIb-IIIa, pp60c-src, pp62c-yes, and GAP associate with a
      membrane skeleton fraction that contains spectrin, vinculin, and talin, 2) the
      association of GP IIb-IIIa with adhesive ligand in a platelet aggregate causes
      components of the membrane skeleton to undergo altered association with
      cytoplasmic actin filaments, and 3) many of the proteins phosphorylated on
      tyrosine residues in activated platelets are components of the cytoskeleton. The
      results imply that the membrane skeleton may play an important role in binding
      signaling molecules at sites of integrin-cytoskeleton interactions and in
      mediating signal transduction events in platelets. Further, GP IIb-IIIa-induced
      redistribution of components of the membrane skeleton and associated signaling
      molecules may represent an important step in regulating integrin-induced motile
      events in platelets.

PMID- 7503993
TI  - A new paradigm for biochemical energy coupling. Salmonella typhimurium nicotinate
      phosphoribosyltransferase.
AB  - The pncB gene of Salmonella typhimurium was used to develop an overexpression
      system for nicotinate phosphoribosyltransferase (NAPRTase, EC 2.4.2.11), which
      forms nicotinate mononucleotide (NAMN) and PPi from nicotinate and alpha-D-5
      phosphoribosyl-1-pyrophosphate (PRPP). NAPRTase hydrolyzes ATP in 1:1 molar
      stoichiometry to NAMN synthesis. Hydrolysis of ATP alters the ratio of
      products/substrates for the reaction nicotinate + PRPP <--> NAMN + PPi from its
      equilibrium value of 0.67 to a steady-state value of 1100. The energy for the
      maintenance of this ratio must come from ATP hydrolysis. However, in contrast to
      other ATP-utilizing enzymes, when all ATP is hydrolyzed the unfavorable
      product/substrate ratio collapses. ATP/ADP exchange results suggest that the
      overall reaction involves a phosphoenzyme (E-P) arising from E.ATP. Km values for
      nicotinate and PRPP each decreased by 200-fold when ATP was present to
      phosphorylate the enzyme. PPi stimulated the ATPase activity of the enzyme to
      Vmax values, suggesting that PPi formation during catalysis provides a trigger
      for cleavage of the putative E-P in the overall reaction and regenerates the low
      affinity form of the enzyme. A model is presented in which alternation of high
      and low affinity forms of NAPRTase provides a "steady-state" coupling between ATP
      hydrolysis and NAMN formation.

PMID- 7503994
TI  - Evidence for a viral aetiology of transient synovitis of the hip.

PMID- 7503995
TI  - A spacer protein in the Saccharomyces cerevisiae spindle poly body whose
      transcript is cell cycle-regulated.
AB  - Monoclonal antibodies against the 110-kD component of the yeast spindle pole body
      (SPB) were used to clone the corresponding gene SPC110. SPC110 is identical to
      NUF1 (Mirzayan, C., C. S. Copeland, and M. Synder. 1992. J. Cell Biol. 116:1319
      1332). SPC110/NUF1 has an MluI cell cycle box consensus sequence in its putative
      promoter region, and we found that the transcript was cell cycle regulated in a
      similar way to other MluI-regulated transcripts. Spc110p/Nuflp has a long central
      region with a predicted coiled-coil structure. We expressed this region in
      Escherichia coli and showed by rotary shadowing that rods of the predicted length
      were present. The 110-kD component is localized in the SPB to the gap between the
      central plaque and the sealed ends of the nuclear microtubules near the inner
      plaque (Rout, M., and J. V. Kilmartin. 1990. J. Cell Biol. 111:1913-1927). We
      found that rodlike structures bridge this gap. When truncations of SPC110 with
      deletions in the coiled-coil region of the protein replaced the wild-type gene,
      the gap between the central plaque and the ends of the microtubules decreased in
      proportion to the size of the deletion. This suggests that Spc110p connects these
      two parts of the SPB together and that the coiled-coil domain acts as a spacer
      element.

PMID- 7503997
TI  - Prefrontal connections of medial motor areas in the rhesus monkey.
AB  - Several areas on the medial surface of the frontal lobe in both monkeys and
      humans, including the supplementary motor area and specific areas within the
      ventral bank of the cingulate sulcus called the cingulate motor areas, have been
      implicated in the initiation and execution of skilled movements. These areas
      project directly to the motor cortex and spinal cord, and, on this basis alone,
      can be considered premotor areas. The present study investigated whether these
      premotor areas are specific targets of prefrontal cortical projections in the
      rhesus monkey and thereby provide links between this association cortex and motor
      effector pathways. Circumscribed injections of wheat germ agglutinin-conjugated
      horseradish peroxidase were placed into different cytoarchitectonic subdivisions
      of prefrontal cortex, and resultant retrograde and anterograde labeling examined
      with respect to designated premotor targets. Conversely, injections were also
      made in the supplementary and cingulate motor areas and labeled cells and
      terminals charted in the prefrontal cortex. A principal finding in this study is
      the identification of multiple prefrontal regions that project to the
      supplementary motor area, the cingulate motor areas, or both. Areas 46, 8a, 9,
      11, and 12 are reciprocally connected with an area of the superior frontal gyrus
      in or near the supplementary motor area at its rostral margin. A smaller
      constellation of prefrontal areas, areas 46, 8a, and 11, is reciprocally
      connected with portions of cingulate cortex that have been classified as premotor
      arm and/or leg representations (Hutchins et al., Exp Brain Res 71:667-672, 1988).
      In accordance with numerous previous reports, prefrontal areas 46, 8a, 9, 10, 11,
      and 12 are reciprocally connected with "nonmotor" subdivisions of cingulate
      cortex. The results presented here specify the corticocortical connections by
      which prefrontal cortex may influence motor output.

PMID- 7503998
TI  - Branching projections from mesopontine nuclei to the nucleus reticularis and
      related thalamic nuclei: a double labelling study in the rat.
AB  - Branching projections from pedunculopontine and laterodorsal tegmental nuclei to
      different thalamic targets were studied by means of a double retrograde tracing
      technique. The results show a topographic distribution of mesopontine neurons
      projecting to different thalamic targets. In addition, the present data
      demonstrate that a small percentage (< or = 5%) of mesopontine neurons projecting
      to the intralaminar nuclei or to the rostral pole of the reticular nucleus
      innervate both these areas by means of branching axons. By contrast, a large
      number of mesopontine neurons projecting to the sensorimotor thalamic nuclei send
      axon collaterals to the caudal part of the reticular nucleus. The present
      findings support the hypothesis of an inhomogeneity of different sectors of the
      thalamic reticular nucleus. Thus, this nucleus can be differentiated into two
      functional areas, in accordance with their connections with functionally
      different cortical fields and thalamic districts. The possibility that these two
      areas of the thalamic reticular nucleus subserve different mechanisms during
      sleep phenomena is discussed.

PMID- 7503996
TI  - Temporal analysis of events associated with programmed cell death (apoptosis) of
      sympathetic neurons deprived of nerve growth factor.
AB  - The time course of molecular events that accompany degeneration and death after
      nerve growth factor (NGF) deprivation and neuroprotection by NGF and other agents
      was examined in cultures of NGF-dependent neonatal rat sympathetic neurons and
      compared to death by apoptosis. Within 12 h after onset of NGF deprivation,
      glucose uptake, protein synthesis, and RNA synthesis fell precipitously followed
      by a moderate decrease of mitochondrial function. The molecular mechanisms
      underlying the NGF deprivation-induced decrease of protein synthesis and neuronal
      death were compared and found to be different, demonstrating that this decrease
      of protein synthesis is insufficient to cause death subsequently. After these
      early changes and during the onset of neuronal atrophy, inhibition of protein
      synthesis ceased to halt neuronal degeneration while readdition of NGF or a cAMP
      analogue remained neuroprotective for 6 h. This suggests a model in which a
      putative killer protein reaches lethal levels several hours before the neurons
      cease to respond to readdition of NGF with survival and become committed to die.
      Preceding loss of viability by 5 h and concurrent with commitment to die, the
      neuronal DNA fragmented into oligonucleosomes. The temporal and pharmacological
      characteristics of DNA fragmentation is consistent with DNA fragmentation being
      part of the mechanism that commits the neuron to die. The antimitotic and
      neurotoxin cytosine arabinoside induced DNA fragmentation in the presence of NGF,
      supporting previous evidence that it mimicked NGF deprivation-induced death
      closely. Thus trophic factor deprivation-induced death occurs by apoptosis and is
      an example of programmed cell death.

PMID- 7503999
TI  - Deafferentation-induced changes in neuropeptides of the adult rat dorsal horn
      following pronase injection of the sciatic nerve.
AB  - The effect of deafferentation on the neuropeptides substance P (SP), calcitonin
      gene-related peptide (CGRP), somatostatin (SS), and cholecystokinin (CCK) in the
      lumbar dorsal horn of the adult rat was examined by the indirect
      immunohistochemical method. Deafferentation was induced by injecting the sciatic
      nerve of anesthetized rats with proteolytic enzymes (20 mg pronase), which cause
      selective death of the nerve's ganglion cells and degeneration of their terminal
      arborization in the spinal cord. The density of immunolabel of each peptide was
      determined by using a computerized densitometry analysis system in two animal
      groups, i.e., short-term (10-13 days after injection) and long-term (4-9 months).
      In both groups, the deafferentation produced a significant ipsilateral depletion
      of CGRP, SP, CCK, and SS immunoreactivity. This depletion was limited to the area
      occupied by the sciatic terminals in the dorsal horn. In the long-term group, the
      loss of CGRP and SP staining was significantly less than that in the short-term
      animals, thus indicating partial recovery. A similar, but not statistically
      significant, trend was observed for CCK and SS. The large decrease in CGRP and SP
      seen in short-term animals reflects the large contribution of the sciatic nerve
      to the lumbar dorsal horn. The partial recovery of peptides demonstrates the
      plasticity of the nervous system and may parallel sprouting of primary afferents
      from other nerves, such as the saphenous nerve, as we have demonstrated in
      previous studies.

PMID- 7504000
TI  - Cortical axon trajectories and growth cone morphologies in fetuses of acallosal
      mouse strains.
AB  - Hereditary absence of the corpus callosum (CC) provides an ideal experiment of
      nature for exploring mechanisms of axon guidance. In this study the prenatal
      development of CC axons in the acallosal mouse strains BALB/cWah1 and 129/ReJ or
      J was compared with normal hybrid mice by using the lipophilic dyes DiI and DiA.
      A few I/LnJ mice were also examined. The time of emergence and growth rate of CC
      axons from four cortical regions (frontal, parietal, temporal, occipital) were
      normal in acallosal strains. Their CC axons arrived at midplane on schedule but
      then often looped back to form the longitudinal Probst bundle. The frequency of
      formation of the Probst bundle was highest for axons from frontal cortex, which
      arrived at midplane first, and lowest for occipital axons, which arrived last.
      Once a few CC axons found a path to the other side via the hippocampal
      commissure, those that arrived later then crossed relatively normally. Some axons
      from the Probst bundle also managed to traverse midline in this manner. When no
      CC axons crossed, almost all of them entered the Probst bundle and eventually
      left it within a few hours to proceed in the ipsilateral white matter, never
      turning back toward midplane. Growth cones approaching midplane ipsilaterally and
      those that had crossed midline and entered contralateral white matter, as well as
      CC axons in the Probst bundle, expressed a normal range of size and complexity.
      These results demonstrate that the problem with callosal agenesis resides not in
      the cells of origin or the axons or growth cones themselves but in the substrates
      of axon guidance at the midsagittal plane.

PMID- 7504001
TI  - Transient neovascularisation of the frog retina during optic nerve regeneration.
AB  - In conditions such as diabetic retinopathy, degenerative events in the retina are
      associated with neovascularisation. It is well established that a proportion of
      retinal ganglion cells die during optic nerve regeneration in the frog. The
      present study has determined whether neovascularisation takes place during this
      regenerative process. To do so, the pattern of blood vessels overlying the
      retinal ganglion cell layer was analysed in the frog Litoria (Hyla) moorei. We
      examined normal animals and those undergoing optic nerve regeneration following
      nerve crush. Blood vessels were visualised by perfusion with Indian ink and
      retinae were prepared as wholeamounts. In normal animals, the vascular tree was
      found to lie superficial to the nerve fibre layer and was more complex in regions
      overlying the area centralis and visual streak. After nerve crush, abnormal blood
      vessels transiently formed between the existing branches of the vascular tree.
      The new vessels were concentrated as an annulus centred on the optic nerve head
      and over the area centralis in midtemporal retina. The neovascularisation became
      most extensive between 6 and 10 weeks postcrush and disappeared by 12 weeks. The
      spatiotemporal sequence of neovascularisation suggests that it is triggered by
      accumulations of degenerating material formed as a proportion of the ganglion
      cells die during optic nerve regeneration.

PMID- 7504002
TI  - Unusual eosinophilic granule cell proliferation in coho salmon (Oncorhynchus
      kisutch).
AB  - Whitish, opaque, coalescing masses were observed coating the visceral organs of
      numerous adult coho salmon when they were dissected for artificial spawning in
      the autumn of 1983 at the Puntledge River hatchery, British Columbia. One
      affected fish was observed in November 1991. Histological examination of 10 of
      these fish (nine in 1983 and one in 1991) revealed that the lesions consisted of
      unusual proliferations of eosinophilic granule cells (EGCs) with some
      characteristics of neoplasia. The proliferative lesions extended throughout the
      gastrointestinal tract and infiltrated through all layers of the gut. Pancreatic
      tissue and adipose tissues associated with the pyloric caeca were also
      infiltrated and replaced by the proliferating EGCs. A mild diffuse infiltration
      was also observed in the spleen, liver and kidney. Histochemical analysis and
      ultrastructural examination showed the proliferating cells to be essentially
      identical with the EGCs which are usually concentrated in the stratum granulosum
      of the intestine in normal salmonid fishes.

PMID- 7504003
TI  - Histological, histochemical and ultrastructural features of hyaline inclusions in
      hepatocytes of striped dolphins (Stenella coeruleoalba).
AB  - Many striped dolphins (Stenella coeruleoalba) which died in the recent
      morbillivirus epizootic in the Mediterranean Sea had hyaline inclusions in
      hepatocytes. We investigated the histological, histochemical and ultrastructural
      features of these inclusions in two affected dolphins. Histochemical tests
      indicated that they contained glycoprotein but not lipid. Ultrastructurally, they
      consisted of granular, moderately electron-dense material, bounded by a membrane.
      A central or eccentric core of highly electron-dense material was usually
      apparent. The inclusions were probably of lysosomal origin.

PMID- 7504004
TI  - The preparation of frozen sections for micrographic surgery. A review of current
      methodology.
AB  - BACKGROUND: Various methods are currently in use for preparing histological
      slides for micrographic surgery. OBJECTIVE: Because many variables contribute to
      the quality preparation of frozen sections, a review of techniques available is
      useful to the Mohs surgeon. TECHNICAL METHODS AND RESULTS: Our techniques as well
      as the published work of others regarding mounting, embedding, freezing, slides,
      fixation, staining, and clearing are reviewed in detail. By the use of the
      options selected we were able to produce, in a short turn-around time, frozen
      sections with excellent quality and minimal artifact. CONCLUSION: Presently all
      preparation techniques may introduce some degree of artifact. However, we feel
      the process described herein is adaptable to all Mohs surgery laboratories and
      will result in high quality specimens with minimal artifact.

PMID- 7504005
TI  - Cutaneous eruptions induced by granulocyte colony-stimulating factor in two cases
      of acute myelogenous leukemia.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induced
      cutaneous eruptions in two cases of acute myelogenous leukemia. In both cases,
      the eruptions appeared during rhG-CSF therapy for neutropenia induced by the
      remission-induction chemotherapy and disappeared rapidly after the discontinuance
      of rhG-CSF therapy. Histopathology of those eruptions revealed dermal cell
      infiltrations consisting of some neutrophils and atypical cells. It was
      interesting that, although there were no leukemic cells in the peripheral blood
      or bone marrow, eruptions containing many leukemic cells appeared. The mechanism
      of the appearance of these eruptions was unclear, but it was considered that a
      few leukemic cells might have responded to rhG-CSF and proliferated in the skin.

PMID- 7504006
TI  - Intracoronary injection of basic fibroblast growth factor enhances angiogenesis
      in infarcted swine myocardium.
AB  - OBJECTIVES: This study was performed to examine the effect of intracoronary
      exogenous basic fibroblast growth factor (bFGF) on angiogenesis in infarcted
      myocardial regions. BACKGROUND: Exogenous bFGF is a potent promoter of
      angiogenesis. Little information is available on its effect on myocardial
      angiogenesis. METHODS: Myocardial infarction was induced in 10 pigs by
      intracoronary injection of microscopic beads. Four pigs served as a control
      group; in six pigs slow-release bFGF was delivered by the beads. Cardiac
      performance was evaluated by repeated echocardiographic measurement and
      angiogenesis was evaluated by immunohistochemical studies 14 days later. RESULTS:
      As compared with control pigs, pigs treated with bFGF had higher microvessel
      counts (mean +/- SEM) in both viable tissue (141 +/- 27 per field vs. 39 +/- 4, p
      = 0.01) and nonviable tissue (329 +/- 26 per field vs. 95 +/- 7, p < 0.001)
      within the infarct area. No significant differences in total regional left
      ventricular wall motion were noted between the two groups throughout the 14-day
      study period. CONCLUSIONS: In the swine, direct intracoronary application of bFGF
      to infarcted myocardium enhances myocardial neovascularization within 2 weeks.

PMID- 7504007
TI  - Distribution of DNA in human Sertoli cell nucleoli.
AB  - For better understanding of nucleolar architecture, different techniques have
      been used to localize DNA within the dense fibrillar component (DF) or within the
      fibrillar centers (FC) by electron microscopy (EM). Since it still remains
      controversial which components contain DNA, we investigated the distribution of
      DNA in human Sertoli cells using various approaches. In situ hybridization (ISH)
      with human total genomic DNA as probe and the use of anti-DNA antibody were
      followed by immunogold detection. This allowed statistical evaluation of the
      signal density over individual components. The Feulgen-like osmium-ammine (OA)
      technique for the selective visualization of DNA was also applied. The anti-DNA
      antibodies detected DNA in mitochondria, in chromatin, and in the DF of the
      nucleolus. ISH using human total genomic DNA showed similar labeling patterns.
      The OA technique revealed DNA filaments in the FC and focal agglomerates of
      decondensed DNA within the DF. We conclude that (a) EM staining techniques that
      utilize colloidal gold appear to be less sensitive for DNA detection than the OA
      method, (b) the DF consists of different domains with different molecular
      composition, and (c) decondensed DNA is not necessarily confined to one
      particular nucleolar component.

PMID- 7504008
TI  - The immunohistochemical heterogeneity of atheroma macrophages: comparison with
      lymphoid tissues suggests that recently blood-derived macrophages can be
      distinguished from longer-resident cells.
AB  - We studied the antigenic markers of macrophages (Mphs) in atherosclerotic human
      arteries by immunohistochemistry and compared them with the patterns in Mph
      subpopulations of tonsil and lymph node, which are also described. The staining
      of atheroma intimal Mphs was assessed semiquantitatively in the subendothelial,
      mid, and outer intima. Three patterns of reactivity with Mph antibodies were
      recognized. (a) Pan-Mph (antibodies HAM56, EBM11, and CD14 group). Staining was
      maximal in the mid-intimal zone. (b) Subendothelial Mphs (anti-muramidase, anti
      alpha-1-antitrypsin and MAC387). In lymphoid tissue, sinusoidal Mphs and a few
      inflammatory Mphs were stained, as well as blood monocytes. This group of
      antibodies recognizes Mphs that are likely to be recently blood-derived (RBD
      Mphs). (c) Antibodies reactive with various histiocyte populations in lymphoid
      tissues (anti-Factor XIII; anti-HLA Class II and LN2) also gave maximal staining
      in the mid-intimal zone, but differences between lesion types suggest that they
      are recognizing heterogeneous subpopulations of Mphs. These observations
      demonstrate the heterogeneity of tissue Mphs and suggest that an insight into the
      dynamics of tissue Mphs can be obtained from the cell phenotype. They indicate
      that all stages of atherosclerosis can have an outward traffic of Mphs from the
      blood through the arterial intima.

PMID- 7504009
TI  - Binding and processing of multimeric vitronectin by vascular endothelial cells.
AB  - The multifunctional adhesive glycoprotein vitronectin (VN) undergoes a unique
      conformational transition from the plasma form into a multimeric form that
      represents the reactive heparin-binding form. In this study we investigated the
      interaction of multimeric vitronectin (VNmult) or VN-gold conjugates (which are
      equivalent in biochemical properties) with confluent and subconfluent monolayers
      of porcine endothelial cells. Time-dependent direct binding of radiolabeled
      VNmult to the luminal face of endothelial cells at 37 degrees C was observed
      which was competed by heparin, whereas plasma VN showed hardly any binding. At 4
      degrees C binding of VNmult remained cell-associated, whereas after 6 hr at 37
      degrees C a major portion of the ligand was translocated through cells and was
      associated with the subcellular matrix. Cytochemical studies with VN-gold
      conjugates were performed to demonstrate uptake of VNmult. At 4 degrees C only
      surface decoration of cells with gold label was seen, which was totally
      reversible in the presence of heparin. Subsequent incubation for various time
      intervals at 37 degrees C revealed disappearance of gold label from the surface
      and accumulation of conjugates in a perinuclear distribution inside the cells as
      judged both by electron microscopy and after silver enhancement by light
      microscopy. Cross-sections of endothelial cells demonstrated the inclusion of VN
      gold conjugates in coated pits, endosomes, and in lysosomal compartments close to
      the nucleus. Within 2-6 hr a portion of VN-gold conjugates had accumulated with
      proteoglycans at the matrix face. These data provide strong evidence for specific
      routing of a portion of VNmult from the circulation into extravascular spaces,
      where the protein is believed to fulfill major adhesive and regulatory functions
      particularly as co-factor in plasminogen activation and immune defense.

PMID- 7504010
TI  - HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted
      from peptide binding motifs.
AB  - The potential value of peptide binding motifs of HLA class I molecules for the
      prediction of viral epitopes presented to T cells has been analyzed for two
      common HLA alleles. CTL generated against type A influenza virus recognize
      peptide epitopes derived from the nucleoprotein (NP) and basic polymerase 1
      presented by HLA-A1, and epitopes derived from NP presented by HLA-A3. Distinct
      peptide binding motifs with characteristic anchor residues were previously
      identified for each of these class I molecules based on the sequences of
      endogenous peptides: for HLA-A1, position 3 = Asp or Glu and position 9 = Tyr;
      for HLA-A3, position 2 = Leu and position 9 = Lys or Tyr. Six peptides containing
      the HLA-A1 binding motif were identified within the sequences of the NP and basic
      polymerase 1 proteins, and one peptide containing the HLA-A3 motif was identified
      in the NP molecule. Three of the six HLA-A1 peptides and the one HLA-A3 NP
      peptide could bind to HLA-A1 or HLA-A3, respectively, in an in vitro peptide
      binding assay. Two of the HLA-A1-binding peptides could sensitize target cells
      for lysis by influenza virus-immune CTL populations restricted by HLA-A1 (NP 44
      52 CTELKLSDY and PB1 591-599 VSDGGPNLY), and the one HLA-A3 NP peptide (NP 265
      273 ILRGSVAHK) could sensitize target cells for lysis by HLA-A3-restricted
      influenza-immune CTL. Each peptide was also shown to be able to induce peptide
      specific class I-restricted CTL in vitro, and the CTL generated against two of
      these peptides could specifically recognize virus-infected targets. Thus, these
      peptide binding motifs can be used to construct immunogenic synthetic epitopes
      which are capable of inducing antiviral T cell-mediated immune responses.

PMID- 7504011
TI  - Administration of anti-CD45 mAb specific for a B cell-restricted epitope
      abrogates the B cell response to a T-dependent antigen in vivo.
AB  - CD45 is a receptor-like protein tyrosine phosphatase expressed exclusively by
      cells of the hemopoietic lineage. Studies in vitro involving treatment of B cells
      with anti-CD45 mAb have demonstrated that ligand binding to CD45 alters the
      cell's response to various activation/differentiation stimuli. In general anti
      CD45 treatment has been shown to exert an inhibitory effect on early activation
      events resulting in the failure of quiescent B cells to enter the cell cycle.
      These studies suggest that CD45 acts as an important regulatory molecule in
      vitro, that controls B cell function. In contrast, little is known concerning the
      role that CD45 plays in vivo regarding regulation of B cell activation and
      differentiation in response to T-dependent Ag. In our study the anti-CD45 mAb
      RA3.6B2, which recognizes a B cell-restricted epitope, was used to examine this
      question. Administration of anti-CD45 mAb in vivo was found to inhibit the
      proliferative response of splenocytes when stimulated with B cell-, but not T
      cell-specific mitogens. Immunization with the T-dependent Ag FITC-KLH in the
      presence of increasing amounts of anti-CD45 mAb resulted in a significant, dose
      dependent inhibition of the plaque-forming cell response. Additionally, anti-CD45
      mAb inhibited the production of FITC-specific serum antibodies indicating that
      the effect was systemic. Finally, anti-CD45 mAb appeared to exert a maximal
      effect at earlier time points, within 48 h of Ag administration, suggesting that
      B cell activation was primarily affected. These results provide evidence to
      support the conclusion that CD45 is an important regulatory molecule that is
      involved in the control of B cell activation in vivo.

PMID- 7504012
TI  - Elevation of intracellular cAMP in human T lymphocytes by an anti-CD44 mAb.
AB  - Regulation of lymphocyte responses to activation of the CD3/TCR complex by other
      cell surface proteins expressed on lymphocytes is a well established phenomenon.
      CD44 is an example of such a cell surface protein. Anti-CD44 mAb have been
      identified which either stimulate or inhibit lymphocyte function. Certain anti
      CD44 mAb augment proliferation and IL-2 production by T cells stimulated through
      the CD2 or CD3/TCR pathways. An anti-CD44 mAb with opposing properties has also
      been identified. This mAb inhibits activation of human T cells by preventing the
      rise in [Ca2+]i stimulated by OKT3. The purpose of experiments reported here was
      to further characterize this phenomenon. The results show that the anti-CD44 mAb,
      212.3, does not inhibit inositol phosphate turnover stimulated by OKT3 but does
      inhibit elevation of intracellular [Ca2+]i in these same cells. Addition of 212.3
      to purified human T cells results in a rapid increase in intracellular levels of
      cAMP. Elevation of cAMP by 212.3 is time- and concentration-dependent. Activation
      of adenylate cyclase by forskolin also results in elevation of intracellular cAMP
      and inhibition of the increase in [Ca2+]i stimulated by OKT3. Taken together,
      these data suggest that CD44 may be positively coupled to adenylate cyclase and
      that activation of adenylate cyclase by the anti-CD44 mAb, 212.3, may mediate the
      inhibition of the OKT3-stimulated elevation of [Ca2+]i.

PMID- 7504013
TI  - Mouse MHC class I-like Fc receptor encoded outside the MHC.
AB  - In many mammalian species antibodies transmitted from the mother provide humoral
      immunity to the young. Maternal IgG from milk is transported across the
      intestinal epithelium of neonatal rats by an Fc receptor (FcRn) that comprises an
      alpha-chain similar to the class I Ag of the MHC and beta 2-microglobulin.
      Suckling mice also acquire antibodies by uptake from the gut. We made a neonatal
      mouse intestinal cDNA library and screened it with a probe encoding rat FcRn
      alpha-chain. The nucleotide and predicted amino acid sequences of the two
      positive clones were very similar to those of rat FcRn. Comparison of the FcRn
      domains to various MHC class I and CD1 molecules suggests a divergence of FcRn
      from MHC early in the mammalian lineage. We expressed one of these cDNA in mouse
      3T3 fibroblasts. Cells that expressed the cDNA product bound the Fc fragment of
      IgG with the same pH dependence as neonatal rat intestinal epithelium. We
      detected RNA that hybridize with the mouse cDNA only in neonatal small intestine
      and fetal yolk sac, two tissues involved in IgG transport. These data show that
      the mouse cDNA code for FcRn alpha-chain. The mouse FcRn alpha-chain is similar
      in sequence to the class I MHC Ag, encoded on chromosome 17 in the mouse.
      However, we find that the mouse FcRn gene lies outside the MHC, on chromosome 7.

PMID- 7504014
TI  - Mapping the major human T helper epitopes of tetanus toxin. The emerging picture.
AB  - Progress on the mapping of Th epitopes of tetanus toxin (tt) has been slow due to
      reliance on studies of clones. In this paper, human Th cell epitopes of tt were
      mapped using proliferation tests on PBMC in response to synthetic peptides. PBMC
      from nine donors were tested over the entire set of tt homologous overlapping
      dodecapeptides. The 1304 peptides were initially tested as 66 pools, each
      containing an average of 20 peptides. PBMC from individual donors responded to as
      few as 1 and as many as 17 of the 66 peptide pools. The sequences responsible for
      proliferation were identified for the two most frequently recognized pools, and
      for another two pools within a major immunodominant region. Three new epitope
      sequences were mapped in detail and based on their recognition by most
      individuals are likely to be promiscuous. A cocktail of peptides including the
      newly identified Th cell epitopes was able to induce proliferation in PBMC from
      24 of 31 tetanus toxoid (TT)-responsive donors. This cocktail is a chemically
      defined reagent that can be used to quantitate in vitro Ag-specific Th cells in
      PBMC from most subjects, and may thus be useful for serial measurements of
      specific immunity such as in subjects undergoing immunotherapy or
      immunosuppressive treatment.

PMID- 7504015
TI  - cDNA cloning and expression of guinea pig neutrophil attractant protein-1 (NAP
      1). NAP-1 is highly conserved in guinea pig.
AB  - cDNA for neutrophil attractant protein-1 (NAP-1, also known as IL-8) was cloned
      from Con A-stimulated guinea pig spleen cells with human NAP-1 cDNA as a probe.
      Guinea pig NAP-1 cDNA is composed of 1433 bp with an open reading frame which
      encodes for a 101-amino-acid protein. Guinea pig NAP-1 had 70% amino acid
      sequence similarity to human NAP-1, which was much higher than a similarity
      between human and guinea pig monocyte chemoattractant protein-1 (MCP-1) (56%).
      Nucleotide sequence similarity within the coding region was 75%. To confirm its
      biological activity in guinea pig, recombinant guinea pig NAP-1 was expressed in
      COS-7 cells then purified. N-terminal sequence analysis gave two different N
      termini at position 23 (Met) or 24 (Val). The two proteins showed their peak
      activity for guinea pig neutrophils at the concentration of 1 microgram/ml (10-7
      M). Despite its high similarity to human NAP-1, the responsiveness of human
      neutrophils to guinea pig NAP-1 was minimum. Recombinant guinea pig NAP-1 caused
      strong neutrophil infiltration after intradermal injection into guinea pig skin.
      Since guinea pig is classified as a rodent, it was of interest to know whether
      human NAP-1 cDNA hybridizes to genomic DNA of other rodents such as mouse or rat,
      in which a NAP-1 homologue has not been found. Under low stringency conditions,
      human NAP-1 cDNA hybridized to human, rabbit, and guinea pig DNA, but not to
      mouse or rat DNA. Unlike NAP-1, human MCP-1 cDNA hybridized to genomic DNA of
      rabbit, guinea pig, mouse, and rat; MCP-1 cDNA have been cloned from these
      species. The apparent absence of a NAP-1 gene in mouse or rat makes this
      chemoattractant unique among the members of the protein family to which NAP-1 and
      MCP-1 belong.

PMID- 7504016
TI  - Implication of HLA-DR residues at positions 67, 71, and 86 in interaction between
      HLA-DR11 and peptide HA306-320.
AB  - To get further insight into the role of three polymorphic DR residues located in
      one alpha-helix of the HLA-DR binding groove, we studied how natural
      substitutions at positions 67, 71, and 86 on DR11 molecules influence MHC binding
      and/or T cell recognition of peptide HA306-320 and of monosubstituted peptide
      analogues. Our results show that: 1) Reactivities of all HA306-320-specific T
      cell clones tested are decreased by DR substitution at position 86 and can even
      be lowered by additional substitutions at position 71, and at positions 71 plus
      67, indicating that these three residues are functionally important. 2) The
      functional effects of substitutions at positions 67, 71, and/or 86 cannot be
      explained by a decreased affinity of HA306-320 for the substituted DR11
      molecules, as determined in binding assays. 3) More likely, they are explained by
      modifications of the conformation, orientation, or location of the peptide once
      bound in the HLA groove, because each individual DR substitution at positions 86,
      71, and 67 differentially affects the binding ability of the same panel of 50
      monosubstituted analogues. 4) This interpretation is reinforced by the
      identification of a small set of monosubstituted analogues that can compensate
      the functional effects of DR substitutions at positions 86, 86 plus 71, or 86
      plus 71 plus 67, and thus restore T cell reactivities. All together these results
      strongly suggest that residues 67, 71, and 86 play a key role in interactions
      with HA306-320, probably by modifying the way the peptide is bound within the
      binding groove of HLA-DR11. Using the same DR11.1-restricted clones, we
      identified putative T cell and DR contact residues of HA306-320 by comparing DR
      binding and T cell-activating capacity of the peptide analogues. This analysis
      suggests that: 1) Residues 310, 311, 312, 313, and 316 are putative TCR contacts.
      2) Peptide HA306-320 anchors to DR11.1 molecules mainly via residue Y-309,
      possibly at the vicinity of DR residue 86, whereas peptide residues 315 and 317
      constitute minor aggregotopes that would be at the vicinity of DR residues 71
      and/or 67. 3) Finally, residues 308, 310, and 314 might also be on the MHC side
      of the DR-peptide-TCR complex.

PMID- 7504017
TI  - Inducible nitric oxide synthase from a rat alveolar macrophage cell line is
      inhibited by nitric oxide.
AB  - The objective of this study was to determine whether inducible nitric oxide (NO)
      synthase from a rat alveolar macrophage cell line (NR8383) activated by LPS plus
      IFN-gamma could be regulated by NO, one of the two products of the enzymatic
      reaction. This study was based on previous observations in this laboratory that
      NO is a negative feedback modulator of constitutive NO synthase from rat
      cerebellum. NO synthase activity was determined by monitoring the formation of 3H
      L-citrulline from 3H-L-arginine in the presence of added cofactors. NO synthase
      catalyzed the conversion of L-arginine to equimolar quantities of NO and L
      citrulline. NO and S-nitrosothiols inhibited NO synthase activity and this effect
      was enhanced by superoxide dismutase and attenuated by oxyhemoglobin. Nitrite and
      nitrate, the oxidation products of NO, as well as L-citrulline, the amino acid
      end-product, produced no significant effects on NO synthase activity. The
      inhibitory effect of NO on NO synthase appeared to be partially reversible upon
      addition of oxyhemoglobin. The inhibitory effect of NO was mimicked by other heme
      ligands including carbon monoxide, cyanide, and manganese-protoporphyrin IX.
      These observations indicate that (1) enzyme-bound heme plays a mechanistic role
      in the catalytic conversion of L-arginine to NO plus L-citrulline; (2) NO may
      function as a negative feedback modulator of inducible NO synthase by interacting
      with enzyme-bound heme; and (3) negative feedback modulation by NO may represent
      a mechanism by which the potentially toxic L-arginine-NO pathway in activated
      alveolar macrophages is turned off.

PMID- 7504018
TI  - Neutrophils roll on E-selectin.
AB  - Using flow conditions that simulate those in post capillary venules, we have
      found that neutrophils attach and roll on a substrate bearing purified E
      selectin. E-selectin resembles P-selectin (CD62) with regard to the dependence of
      attachment efficiency on wall shear stress and selectin density. In contrast,
      once attached, neutrophils form rolling adhesions on E-selectin that are much
      stronger than those on P-selectin. Rolling velocities on E-selectin are slower
      and have less variance than on P-selectin. With increasing shear stress, rolling
      velocities reach a plateau level that is dependent on E-selectin density,
      suggesting that the number of receptor-ligand bonds and the bond dissociation
      rate limit rolling velocity, and that the bonds are not broken by the applied
      force.

PMID- 7504019
TI  - Intravenous interleukin-8 inhibits granulocyte emigration from rabbit mesenteric
      venules without altering L-selectin expression or leukocyte rolling.
AB  - Injection (i.v.) of the granulocyte chemoattractant/activator IL-8 has been shown
      to reduce neutrophil recruitment into dermal inflammatory sites in vivo. To
      further investigate the mechanism of this phenomenon, we examined the effect of
      i.v. [Ser-IL-8]72 (12-20 micrograms/kg) on leukocyte rolling and chemoattractant
      induced emigration in mesenteric venules of New Zealand White rabbits and on
      expression of L-selectin (mAb LAM1-3) and CD18 (mAb 60.3) on circulating rabbit
      granulocytes. Within 1 min of IL-8 i.v., granulocytes virtually disappeared from
      carotid blood samples for approximately 5 min. Concomitantly, the flux of rolling
      leukocytes in mesenteric venules fell from 83 +/- 21 to 2 +/- 1 leukocytes/min.
      Both rolling leukocyte flux and systemic granulocyte count returned to or
      exceeded control values within less than 30 min. The chemoattractant/activator
      FMLP (0.15 microgram/kg i.v.) produced similar results. A second i.v. injection
      of IL-8 or FMLP, 90 min after the first challenge, had equipotent effects. Local
      extravascular application of IL-8 via micropipette close to a venule induced
      adhesion and emigration of 63 +/- 21 leukocytes per site before, but only 26 +/-
      9 leukocytes per site 50 to 75 min after i.v. IL-8, when systemic granulocyte
      count and rolling leukocyte flux had reached or exceeded control values. This was
      not due to agonist-specific desensitization, because a similar reduction of
      leukocyte emigration was seen after FMLP i.v. Rabbit granulocytes circulating in
      vivo uniformly expressed near-control levels of L-selectin at all times between 3
      and 360 min after IL-8 i.v. CD18 expression transiently increased after IL-8 i.v.
      and returned to base line by 90 min. These findings show that IL-8 i.v. reduces
      granulocyte recruitment to inflammatory sites by inhibiting function(s) necessary
      for transmigration that are independent of L-selectin and subsequent to rolling.

PMID- 7504020
TI  - Protective effects of selectin chimeras in neutrophil-mediated lung injury.
AB  - Recombinant selectin chimeric molecules featuring the joining of the
      extracellular domains of L-, P-, and E-selectin to the CH2 and CH3 domains of
      human IgG1 have been evaluated for their ability to protect against neutrophil
      dependent lung injury in rats after systemic activation of C caused by vascular
      infusion of cobra venom factor (CVF) or lung injury that follows intrapulmonary
      deposition of IgG immune complexes. Previous studies using anti-selectin
      antibodies have suggested that the former model is P-selectin dependent, whereas
      the latter is E-selectin dependent. Requirements for L-selectin have not been
      identified because of lack of reagents. For the current studies employing the CVF
      model of lung injury, infusion of P-selectin-Ig chimera reduced injury (as
      assessed by changes in permeability and hemorrhage) in a dose-dependent manner,
      with parallel reductions in lung myeloperoxidase (MPO) content. Similar results
      were obtained with the L-selectin-Ig chimera, whereas the E-selectin-Ig chimera
      was not protective and failed to alter MPO content. In contrast, in the IgG
      immune complex model of lung injury, the L- and E-selectin-Ig chimeras both
      showed dose-related protective effects and reductions in MPO content, whereas the
      P-selectin-Ig chimera failed to protect against injury and did not alter MPO
      content in this model of lung injury. In all cases of blocking of injury, this
      was incomplete, suggesting multi-selectin engagement or inadequate amounts of
      selectin-Ig chimeras employed. These data indicate that neutrophil recruitment
      and attendant lung injury in the CVF model are L- and P-selectin dependent and E
      selectin-independent, whereas in the IgG immune complex model, neutrophil
      recruitment and lung injury are L- and E-selectin-dependent but independent of P
      selectin. Thus, differing selectin requirements for acute inflammatory lung
      injury have been identified.

PMID- 7504021
TI  - Differential expression in rheumatoid synovium and synovial fluid of alpha 4 beta
      7 integrin. A novel receptor for fibronectin and vascular cell adhesion molecule
      1.
AB  - T lymphocyte adhesion to vascular endothelium plays an important role in the
      immunopathogenesis of rheumatoid arthritis. The migration of T lymphocytes into
      the synovium is mediated by a variety of adhesion molecules, notably the
      integrins. We have prepared Act I, a murine mAb that identifies a novel integrin
      termed alpha 4 beta 7. The natural ligands for alpha 4 beta 7 are vascular cell
      adhesion molecule-1 and fibronectin; both molecules are up-regulated in the
      rheumatoid synovium. We investigated the expression of alpha 4 beta 7 in the
      three compartments of rheumatoid arthritis, the peripheral blood, synovial fluid,
      and synovial membrane, utilizing the FACS and immunoperoxidase microscopy of
      frozen tissues. The results of our experiments show a striking differential
      expression of alpha 4 beta 7 integrin in rheumatoid arthritis. Sixty-two percent
      of synovial membrane T cells expressed high density alpha 4 beta 7, in contrast
      to only 4.7% of synovial fluid and 9.1% of PBL. These data suggest that the
      expression of alpha 4 beta 7 integrin may provide a mechanism whereby certain T
      cells adhere to rheumatoid synovium while others remain in the synovial fluid.
      The augmented expression of alpha 4 beta 7 in the synovial membrane T cells may
      contribute to the development and perpetuation of rheumatoid arthritis.

PMID- 7504022
TI  - Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol
      myristate acetate and anti-CD44 monoclonal and polyclonal antibodies.
AB  - CD44 molecules are comprised of multiple alternatively spliced forms and are
      associated with diverse functions such as mediation of carcinoma metastasis and T
      cell coactivation. To study the function of individual CD44 isoforms, we have
      transfected CD44 isoforms into CD44-negative Jurkat T cells and produced cloned
      Jurkat cell lines that are stably transfected with either a CD44 isoform
      containing no alternatively spliced insert (CD44H) or a CD44 variant (CD44E)
      containing an insert of 132 amino acids derived from exons 12, 13, and 14 of the
      CD44 gene. We found that neither CD44H- nor CD44E-transfected Jurkat T cells
      constitutively bound hyaluronan (HA), whereas PMA treatment induced Jurkat cells
      transfected with CD44H but not CD44E to bind HA. CD44 mAb against noninsert
      regions of the CD44 extracellular domain (A3D8, A1G3) and polyclonal antisera
      against the COOH-terminal extracellular glycosaminoglycan region of CD44H (anti
      6A serum) both induced CD44H-transfected cells to bind HA, whereas only one CD44
      mAb (A1G3) induced CD44E-transfected Jurkat T cells to bind HA. Studies of Jurkat
      cells transfected with CD44H forms with truncations of the CD44 cytoplasmic
      domain demonstrated that the cytoplasmic COOH-terminal 52 amino acids were
      critical for binding of HA to the CD44 extracellular domain. Thus, these data
      underscore the importance of the CD44 cytoplasmic domain in the function of the
      extracellular portion of CD44H, and demonstrate a role for ligation of human CD44
      isoforms at multiple distinct sites in regulation of expression of CD44 binding
      to HA.

PMID- 7504023
TI  - Characterization of dermal dendritic cells obtained from normal human skin
      reveals phenotypic and functionally distinctive subsets.
AB  - The relative contribution of dermal-derived immunocompetent cells to the overall
      immunologic response in skin has been hampered by the lack of appropriate
      isolation techniques. In this report, we provide a purification schema that
      reliably yields highly purified populations of dermal dendritic cells (DDC).
      These cells are motile, express high levels of class II MHC antigens that
      decorate their cytoplasmic dendritic processes, and lack numerous B cell, T cell,
      and natural killer cell antigens. Using a broad panel of 45 different antibodies,
      an extensive phenotypic analysis was completed, revealing distinctive profiles
      for subsets of DDC. Despite homogeneous light scatter profile and cytologic
      appearance, three subsets of DDC could be distinguished by phenotypic and
      functional criteria. All DDC, but not epidermal Langerhans cells, express factor
      XIIIa. By triple color cell staining the relative distribution of factor XIIIa
      positive DDC is as follows: subset 1, 65% to 70% of total DDC express neither
      CD1a nor CD14; subset 2, 15% to 20% of total DDC express CD1a but not CD14; and
      subset 3, 10% to 15% of total DDC express CD14 but not CD1a. The CD14-negative
      subset of DDC were shown to be as potent stimulators of allogeneic mixed
      lymphocyte reactions as Langerhans cells or blood-derived dendritic cells.
      However, DDC subsets differed in their ability to support autologous T cell
      proliferation in response to the mitogenic lectin PHA or bacterial-derived
      superantigen. In these assays, subsets 1 and 2 were significantly more potent as
      antigen-presenting cells compared with subset 3. Thus, normal skin contains at
      least three separate populations of DDC, which have distinctive phenotypic
      markers and immunologic capabilities.

PMID- 7504024
TI  - VH4.21-encoded natural autoantibodies with anti-i specificity mirror those
      associated with cold hemagglutinin disease.
AB  - The Ig VH regions of virtually all human pathogenic cold agglutinin (CA) anti-i/l
      autoantibodies are encoded by a single Ig VH gene segment, VH4.21, in conjunction
      with a highly variable CDR3 structure. The anti-I specificity is often associated
      with V kappa III-encoded L chains, whereas anti-i autoantibodies appear to use a
      broader array of kappa and lambda VL gene segments. B cells expressing VH4.21 are
      abundantly present in adult lymphoid tissues from healthy individuals but their
      relationship with B cells secreting pathogenic CA is unknown. Herein we have
      analyzed the distribution of VH4.21-expressing B cells in fetal, neonatal, and
      adult B cell populations using the monoclonal anti-VH4.21 antibody 9G4. In
      addition, we have analyzed the anti-i and anti-I binding capacity and V regions
      of 19 VH4.21-encoded mAb secreted by cord and adult blood-derived cell lines from
      healthy individuals. The results show that VH4.21 expressing B cells are
      overrepresented in all repertoires studied and are evenly distributed over cord
      blood CD5+ and CD5- B cell populations. VH4.21-encoded H chains strongly
      predispose for anti-i binding capacity, regardless of the VL regions or H chain
      CDR3 structure. The avidity of some of these antibodies was similar to those of
      pathogenic CA. In addition, we found evidence for monospecific anti-I binding in
      antibodies encoded by other members of the VH4 gene family. We conclude that
      VH4.21-encoded antibodies with anti-i specificity from the normal B cell
      repertoire mirror their pathogenic counterparts and that naturally occurring anti
      I antibodies may be encoded by a more diverse array of VH4 genes.

PMID- 7504025
TI  - IgG antibodies from patients with bullous pemphigoid bind to fusion proteins
      encoded by BPAg1 cDNA.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized in
      part by the presence of circulating and tissue-bound IgG antibodies directed
      against the epidermal basement membrane zone. IgG from over 95% of patients with
      BP have been shown to immunoprecipitate a 230-kD epidermal protein, BPAg1, which
      has been cloned and sequenced. Although sera from almost all patients with BP
      react with the 230-kD BP antigen the specific epitope(s) of BPAg1 that IgG binds
      is not known. We have generated fusion proteins from the 230-kD BP antigen cDNA
      and analyzed sera from patients with BP for binding to these fusion proteins by
      immunoblot. Sera from 21 of 30 (70%) patients with BP reacted with FP3A (amino
      acid 873-1193) compared to four of 13 (30%) normal subjects (p < 0.02). Sera from
      10 of 30 (33%) patients reacted with FP7 (AA1623-1812) and to FP3 (AA1003-1193),
      compared to one of 22 (5%) and 0 of 19 (0%) controls, respectively. No
      significant reactivity was noted against two other fusion proteins (FP6, FP9).
      Twenty-four of 30 (80%) patients with BP reacted to at least one of three fusion
      proteins (FP3, FP3A, FP7) compared to three of 11 (27%) of the control subjects
      (p < 0.003). Fusion proteins FP3, FP3A, and FP7 are at the amino- or carboxyl
      terminal regions of the putative central alpha-helical coiled-coil rod domain of
      BPAg1, which has been postulated to be involved in the self-aggregation of BPAg1.
      These findings demonstrate that patients with bullous pemphigoid react with
      multiple regions of BPAg1 and suggest that part of the pathologic consequences of
      these auto-antibodies in patients with bullous pemphigoid may be by the
      disruption of the normal self-aggregation of the BPAg1.

PMID- 7504026
TI  - Hyaluronan is inversely correlated with the expression of CD44 in the dermal
      condensation of the embryonic hair follicle.
AB  - Previously, we have shown that CD44 (the hyaluronan receptor) was involved in the
      degradation of hyaluronan. In the present study, we examined the distribution of
      CD44 and hyaluronan in the skin of embryonic and mature mice. During embryonic
      development, CD44 was prominently expressed by the condensed mesenchymal cells
      involved in the formation of the hair follicles, but was absent from the
      surrounding interstitial cells. The cells of the dermal condensation expressed
      CD44 throughout the development of the hair follicle; however, once the hair
      follicle reached maturity, the mesenchymal cells of the dermal papilla no longer
      expressed this molecule. In contrast to the above, the distribution of hyaluronan
      was reversed from that of CD44. Hyaluronan was widespread throughout the
      embryonic dermis, but was conspicuously absent from the regions of the dermal
      condensation. This arrangement persisted through the development of the hair
      follicle; however, in the mature hair follicle, hyaluronan reappeared in the
      dermal papilla. Thus, in the embryonic dermis, the expression of CD44 and
      hyaluronan were complementary to each other. However, in the adult skin, only
      minor changes were detected in the levels of CD44 and hyaluronan associated with
      the cells of the dermal condensation during the hair cycle. When organ cultures
      of embryonic mouse skin were treated with Streptomyces hyaluronidase, the
      interstitial mesenchymal cells became compacted, indicating that the removal of
      hyaluronan leads to the condensation of these cells. The results of this study
      are consistent with the hypothesis that the expression of CD44 by the inductive
      mesenchymal cells allows them to degrade hyaluronan in a localized region,
      leading to formation and maintenance of the dermal condensation.

PMID- 7504027
TI  - Expression of an epitope as detected by the novel monoclonal antibody 4F7 on
      dermal and epidermal dendritic cells. I. Identification and characterization of
      the 4F7+ dendritic cell in situ.
AB  - Ears of Balb/c mice were treated epicutaneously with 0.5% 2,4
      dinitrofluorobenzene (DNFB) to obtain monoclonal antibodies characterizing
      molecules on epidermal dendritic cells that are involved in the induction and
      elicitation of allergic contact dermatitis. Six hours after this treatment,
      epidermal cells were prepared from the ear skin, and Ia-positive cells were
      enriched by indirect panning and injected into rats. Hybridomas were generated
      and supernatants were screened for antibodies on ear skin from DNFB-treated and
      untreated animals. A clone (4F7) was isolated and characterized by
      immunohistochemistry and immunoelectron microscopy on murine skin and other
      organs. The monoclonal antibody 4F7 (IgG1) recognized distinct dendritic cells in
      the dermis and very few dendritic cells in the paracortical area of the lymph
      nodes, the white pulp of the spleen, and the mucosa of the large intestine in
      normal animals. By fluorescence activated cell sorter analysis, it stained about
      1.64% of the dermal and no epidermal cells in the skin of untreated animals.
      Approximately 50% of the dermal 4F7+ cells expressed Ia molecules on their
      surface. Six hours after application of 0.5% DNFB, the expression of the 4F7
      antigen was strongly enhanced in vivo on dendritic cells in both the dermis and
      epidermis. About 15% of the epidermal dendritic cells expressing 4F7 exhibited
      Birbeck granules, the other Birbeck granule-negative cells resembled
      indeterminate dendritic cells (IDCs). The dermal and epidermal 4F7+ cells could
      be highly (98%) enriched with 4F7-labeled immunomagnetic particles. Transmission
      electron microscopic analysis of such preparations showed typical characteristics
      of dendritic cells with 50% or 100%, respectively, of these cells expressing Ia
      molecules on their cell membrane. The results suggest that the 4F7 epitope is
      expressed on dendritic cells related to Langerhans cells and is upregulated by an
      inflammatory stimulus.

PMID- 7504028
TI  - Cytopathic effect in human papillomavirus type 1-induced inclusion warts: in
      vitro analysis of the contribution of two forms of the viral E4 protein.
AB  - Myrmecia warts induced by human papillomavirus type 1 (HPV1) are characterized by
      abundant eosinophilic inclusions associated with HPV1 E4 gene products. The major
      HPV1 E4 proteins are a 17-kilodalton (kDa) E1-E4 fusion protein and a 16-kDa
      species lacking the five E1 amino acids and a few E4 residues. To study the
      contribution of E4 proteins to the formation of myrmecia inclusions, we used a
      previously designed transient expression system in the rabbit VX2-R keratinocyte
      line. We find that the E1-E4 and an E4 protein without the E1 residues (E4-3200)
      form eosinophilic inclusions. Ultrastructural and immunoelectron microscopic
      studies show that the electron-dense, keratohyalin-like myrmecia inclusions are
      recognized by anti-E4 antibodies. They are associated with tonofilament bundles
      at their periphery in the cytoplasm or free of filaments in the nucleus. The E1
      E4 inclusions formed in vitro are also homogeneously electron dense, and are
      usually associated with tonofilaments at their periphery in the cytoplasm and
      free of filaments in the nucleus. The E4-3200 inclusions are exclusively
      cytoplasmic and heterogeneously electron dense, with a fibrillar structure made
      of entangled 10-nm filaments. The expression of either protein in VX2-R cells
      does not result in the collapse of the cytokeratin network, as shown by
      immunofluorescence double-labeling experiments. This is in contrast to data
      reported for the HPV16 E1-E4 protein. Our findings indicate that the E1-E4
      protein by itself accounts for the formation of myrmecia inclusions, and suggest
      that the five N-terminal E1 amino acids play a major role in the interaction of
      E4 proteins with intermediate filaments.

PMID- 7504029
TI  - Regulation of expression of B7 by murine Langerhans cells: a direct relationship
      between B7 mRNA levels and the level of surface expression of B7 by Langerhans
      cells.
AB  - Cultured BALB/c epidermal Langerhans cells express high levels of the
      costimulatory molecule B7 on their surfaces relative to levels expressed on fresh
      Langerhans cells. Quantitation of relative amounts of B7 mRNA in fresh epidermal
      cells and cultured epidermal cells following amplification of mRNA signals via
      reverse transcriptase-polymerase chain reaction, hybridization of PCR products
      with radiolabeled internal oligonucleotide probes, resolution of hybrids in non
      denaturing polyacrylamide gels, and detection by autoradiography revealed
      dramatically (approximately one thousandfold) higher levels of B7 mRNA in
      cultured epidermal cells (10-40% I-A+) as compared with fresh epidermal cells (1
      4% I-A+). Levels of B7 mRNA in cultured epidermal cells were also substantially
      greater than those detected in a reference B lymphoma cell line (CH-1). Analysis
      of B7 mRNA expression in subpopulations of cultured epidermal cells demonstrated
      that essentially all of the B7 mRNA was present in Langerhans cells; cells
      bearing I-A and CD45 antigens. Cultured keratinocytes did not contain appreciable
      amounts of B7 mRNA. These results are consistent with previous data regarding
      surface expression of B7 by cLC and also demonstrate that fLC are essentially
      devoid of B7 mRNA and surface protein.

PMID- 7504030
TI  - Evidence against keratin gene mutations in a family with ichthyosis hystrix Curth
      Macklin.
AB  - Ichthyosis hystrix Curth-Macklin is a rare autosomal dominant disease
      characterized clinically by hyperkeratosis and ultrastructurally by disruption of
      the keratin intermediate filament network of suprabasal keratinocytes. We have
      used linkage analysis to test whether a keratin gene mutation might underlie this
      disease. This analysis excluded the keratin gene loci as the sites for the
      disease-causing mutation in one affected kindred.

PMID- 7504032
TI  - Functional conservation of the neutralizing domains on the external envelope
      glycoprotein of cosmopolitan and melanesian strains of human T cell
      leukemia/lymphoma virus type I.
AB  - To determine if the immunodominant neutralizing epitopes on the external envelope
      glycoprotein of the recently identified sequence variants of human T cell
      leukemia/lymphoma virus type I (HTLV-I) from Melanesia are functionally
      conserved, sera from Japanese patients with adult T cell leukemia and from HTLV-I
      infected Melanesians of Papua New Guinea and the Solomon Islands were tested for
      neutralizing antibodies by use of vesicular stomatitis virus pseudotypes bearing
      envelope antigens of Japanese and Melanesian HTLV-I strains. Neutralizing
      antibody titers of the Japanese and Melanesian sera and of monoclonal and
      polyclonal antibodies directed against a known neutralizing epitope on the
      external envelope glycoprotein of HTLV-I were equivalent against the Japanese and
      Melanesian HTLV-I pseudotypes. The demonstrated two-way cross-neutralization
      between Japanese and Melanesian strains of HTLV-I indicates that their antigenic
      determinants for neutralization are functionally indistinguishable and that HTLV
      I exists as a single serotype worldwide.

PMID- 7504031
TI  - High prevalence of hepatitis C virus (HCV) RNA in dialysis patients: failure of
      commercially available antibody tests to identify a significant number of
      patients with HCV infection. Copenhagen Dialysis HCV Study Group.
AB  - Results of serologic tests were correlated with hepatitis C virus (HCV) viremia,
      determined by a cDNA polymerase chain reaction assay to detect HCV RNA, in 340
      Danish dialysis patients; of these, 28 (8.2%) were positive for antibodies to HCV
      (anti-HCV) with second-generation ELI-SAs. HCV RNA was found in sera from 27 of
      these 28 anti-HCV-positive patients. However, 8 dialysis patients had detectable
      levels of HCV RNA but were anti-HCV-negative with second-generation ELISAs. Among
      the 35 HCV-infected dialysis patients 16 were positive, 7 indeterminate, and 12
      negative with the second-generation RIBA. More than 60% of patients with evidence
      of ongoing liver disease had HCV infection. Thus, current commercially available
      antibody tests did not accurately reflect the HCV status in dialysis patients. A
      relatively high prevalence (> 10%) of HCV RNA, closely associated with liver
      disease, was found among dialysis patients in a low-prevalence area of the world.

PMID- 7504033
TI  - Antiinflammatory effects in experimental meningitis of prokaryotic peptides that
      mimic selectins.
AB  - The lectin domains of two subunits of pertussis toxin, S2 and S3, share amino
      acid sequence similarity with the lectin domains of the eukaryotic selectin
      family. During inflammation, selectins appear on endothelial cells and promote
      recruitment of leukocytes by reversibly binding carbohydrates. Synthetic peptides
      representing the carbohydrate recognition domains of S2 and S3 competitively
      inhibited adherence of neutrophils to endothelial cells in vitro. For some
      peptides, this antiinflammatory effect occurred without up-regulation of the
      function of the leukocyte integrin CD11b/CD18. Intravenous administration of
      peptides to animals with meningitis disrupted recruitment of leukocytes into the
      cerebrospinal fluid. These findings indicate that peptides derived from
      prokaryotic members of the selectin family have therapeutic antiinflammatory
      potential.

PMID- 7504034
TI  - Monoclonal anti-lipid A IgM antibodies HA-1A and E-5 recognize distinct epitopes
      on lipopolysaccharide and lipid A.
AB  - Specific binding of two monoclonal IgM antibodies previously investigated as
      therapeutic agents for treating gram-negative septic shock, HA-1A and E5, was
      assessed with respect to lipid A and lipopolysaccharide (LPS). Both antibodies
      bound to lipid A; however, binding of HA-1A was significantly greater than that
      of E5 to LPS derived from rough strains of bacteria. Reciprocal competitive
      inhibition experiments supported the concept that HA-1A and E5 bind to distinct
      epitopes on lipid A. Further, competitive inhibition studies using a monoclonal
      anti-idiotype antibody with specificity for the variable region of HA-1A
      suggested that HA-1A and E5 do not share a common idiotype. Finally, studies
      using double-stranded DNA as antigen indicated that E5 but not HA-1A will bind to
      DNA. Collectively, these data indicate that HA-1A and E5 are different lipid A
      specific antibodies that bind to distinct epitopes on lipid A.

PMID- 7504035
TI  - Effects of stem cell factor and granulocyte colony-stimulating factor on
      granulocyte recovery and Candida albicans infection in granulocytopenic mice.
AB  - The combined action of stem cell factor (SCF) and granulocyte colony-stimulating
      factor (G-CSF) on granulocyte recovery and infection with Candida albicans was
      studied. In mice rendered granulocytopenic with 200 mg/kg cyclophosphamide, daily
      coinjection of SCF (100 micrograms/kg) and G-CSF (10 micrograms/kg) for 5 days
      synergistically stimulated granulocyte recovery compared with either factor
      alone. Growth of C. albicans in the kidneys of granulocytopenic mice with
      experimental C. albicans infection was reduced by the combined regimen to 25% of
      that in vehicle-treated controls (P = .018), whereas either factor administered
      alone in the same doses had no effect. The combined regimen also significantly
      protected against lethal infection with C. albicans (P < .01). Either factor
      administered alone in the same doses had no effect on lethality compared with
      vehicle-treated controls. The combination of SCF and G-CSF may be useful in the
      treatment of infections with C. albicans in the granulocytopenic host.

PMID- 7504036
TI  - Longitudinal analysis of the humoral immune response to human immunodeficiency
      virus type 1 (HIV-1) gp160 epitopes in rapidly progressing and nonprogressing HIV
      1-infected subjects.
AB  - Antibody response to conserved human immunodeficiency virus type 1 (HIV-1)IIIB
      gp160 epitopes was longitudinally examined in HIV-1-infected persons. Twelve
      hundred individuals were evaluated, and sequential sera from 25 rapidly
      progressing (RP) and 30 nonprogressing (NP) subjects collected over an average of
      4 years were examined. Initial sera from the RP group contained greater
      reactivity to a gp120 epitope defined by peptide 503-528 than did sera from the
      NP group (P < .001). Reactivity declined with sequential sera for the RP group,
      paralleling disease progression. Conversely, antibody recognition to this site
      developed in 23% of the NP group with time. However, 60% of the NP group never
      developed a response to this epitope. This suggests sequential examination of
      antibody response to an epitope within the gp120 carboxyl-terminus may have
      prognostic significance. No association between antibodies directed against the
      gp160 epitopes and in vitro neutralizing activity against HIV-1IIIB was observed.

PMID- 7504037
TI  - Influence of whole-body hyperthermia on natural cytotoxicity of liver blood-borne
      sinusoidal cells.
AB  - Rat liver sinusoidal cytotoxic cells were examined after exposure to in vivo and
      in vitro hyperthermia at 40-41 degrees C. Whole-body hyperthermia lasting for 4 h
      caused a decrease in the cytotoxic activity of liver sinusoidal washout cells
      against YAC-1 and K562 cells. Surprisingly, the percentage of washout cells with
      morphology of LGL (large granular lymphocyte) increased both in the liver washout
      and in portal blood compared to control normothermic animals. The proportions of
      phenotypically characterized cell subpopulations isolated from liver sinusoids
      did not change. Elimination of i.v. injected 125I-labelled K562 cells was
      decreased during hyperthermia. In vitro incubation of liver sinusoidal cytotoxic
      cells for 3 h at 41 degrees C decreased their cytotoxic activity by affecting the
      process of effector-target cell binding. However, once the effector-target cell
      conjugates were formed, the cytotoxic process proceeded as in normothermic
      conditions. These data suggest that inhibition of liver sinusoidal cytotoxic cell
      activity after hyperthermia may be a result of deficient target cell recognition
      by the effector cell.

PMID- 7504038
TI  - [Clinical study of heart rate abnormality--special reference to myocardial ion
      channels].

PMID- 7504039
TI  - [Changing pattern and prevention of infectious diseases complicated with severe
      hematologic diseases].

PMID- 7504040
TI  - [Myelodysplastic syndrome].

PMID- 7504042
TI  - A quantitative ELISA for the measurement of complexes of prostate-specific
      antigen with protein C inhibitor when using a purified standard.
AB  - The serine protease inhibitor protein C inhibitor is present in semen at a
      relatively high concentration and forms in vivo complexes with two plasminogen
      activators also present in semen, urokinase-type and tissue-type plasminogen
      activators. Therefore, the fact that prostate-specific antigen (PSA), a major
      prostate enzyme, complexes and inactivates protein C inhibitor (PCI) in semen
      could have implications in human reproduction. The present study was undertaken
      to develop an enzyme-linked immunosorbent assay (ELISA) for complexes of PSA with
      PCI (PSA:PCI) with purified PSA:PCI complexes as a standard. Seminal plasma was
      utilized as the starting material for purification of complexes by affinity
      chromatography on heparin-Sepharose and gel filtration. The final preparation
      contained equimolar concentrations of PSA and PCI and was used for calibration of
      an ELISA for PSA:PCI complexes involving polyclonal anti-PSA and horseradish
      peroxidase-labeled anti-PCI antibodies. The ELISA had a detection limit of about
      0.2 ng/ml of complex and was specific for PSA:PCI complexes because no color was
      developed at PSA or PCI concentrations up to 100 microgram/ml. Normal plasma or
      plasma from patients with prostate carcinoma who had high PSA levels had no
      detectable PSA:PCI complexes. Seminal plasma from voluntary donors collected in
      the absence of inhibitors and incubated at room temperature for at least 3 hours
      had PSA:PCI complex levels ranging from 30 to 46 micrograms/ml, accounting for up
      to 34% of the total PCI in seminal plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504041
TI  - Endothelin-1 gene expression in human pheochromocytoma.
AB  - We examined expression of human endothelin-1 (ET-1) in adrenal tissues removed
      from five patients with pheochromocytomas and two patients with aldosterone
      producing adenomas. The pheochromocytomas contained a 2.3 kilobase ET-1
      transcript, which was not found int he aldosteronomas. Constitutive expression of
      ET-1 varied in magnitude among the pheochromocytomas but was generally at a low
      level. Immunohistochemical staining of the pheochromocytomas with an antiserum to
      human ET-1 showed the presence of immunoreactive ET-1 as well. The presence of ET
      1 messenger ribonucleic acid and ET-1 immunoreactivity in human pheochromocytomas
      suggests a possible paracrine role for this peptide in human chromaffin cells.

PMID- 7504043
TI  - Inhibition by aprotinin.

PMID- 7504044
TI  - Selective inhibition of antigen-specific T lymphocyte proliferation by acute
      ethanol exposure: the role of impaired monocyte antigen presentation capacity and
      mediator production.
AB  - Ethanol consumption is associated with impaired immunity. Our data demonstrate
      that even a single dose of a biologically relevant concentration (25-150 mM) of
      ethanol can down-regulate antigen-specific T lymphocyte proliferation. In
      contrast, ethanol augmented mitogen-induced T cell proliferation, suggesting that
      its inhibitory effect on antigen-specific T cell proliferation was due to its
      effects on monocytes (m phi s) rather than on T cells. The immunodepressive
      effects of ethanol on m phi antigen-presenting cell (APC) capacity were
      manifested whether alcohol treatment was limited to the antigen uptake-processing
      period only or was present during the entire period of antigen presentation.
      These inhibitory effects of ethanol were also evident on both the high-antigen
      presenting, Fc gamma RI-negative (-31 +/- 17%), and low-antigen-presenting, Fc
      gamma RI-positive (-42 +/- 15%) m phi subpopulations. Further analysis
      demonstrated that ethanol inhibits the production of interleukin-1 beta (IL-1
      beta) and induces transforming growth factor beta (TGF-beta) and prostaglandin E2
      (PGE2), monocyte-derived mediators that can affect T cell proliferation. Ethanol
      resulted in a dose-dependent down-regulation of secreted and cell-associated IL-1
      beta protein as well as IL-1 beta mRNA levels induced by adherence or bacterial
      stimulation. The causal relationship between decreased m phi IL-1 beta
      production, elevated TGF-beta levels, and the decreased m phi APC capacity was
      further substantiated when exogenous IL-1 beta protein or anti-TGF-beta
      neutralizing antibody prevented the down-regulatory effect of ethanol on antigen
      specific T cell proliferation. Utilizing a cyclooxygenase inhibitor, we also
      demonstrated that the ethanol-induced decrease in m phi APCs is not mediated by
      enhanced PGE2 production.

PMID- 7504045
TI  - Detection of intracellular interferon-gamma by light microscopy using an
      immunoperoxidase technique: correlation with the corresponding mRNA and protein
      product.
AB  - Identifying individual cytokine-producing cells may help to acquire insight into
      immunological processes. This study was designed to adapt a technique for the
      detection of individual cytokine-producing cells from an immunofluorescence to an
      immunoperoxidase staining procedure. The production of interferon-gamma (IFN
      gamma) by anti-CD3-activated cloned human T cells was used as a model system.
      After the conditions for the staining procedure were optimized, the
      immunoperoxidase technique was slightly more sensitive than the
      immunofluorescence technique. The intracellular staining for IFN-gamma was
      preceded or paralleled by IFN-gamma mRNA production and followed by accumulation
      of IFN-gamma in the supernatant. It is concluded that intracellular IFN-gamma can
      easily be detected using an immunoperoxidase procedure. This procedure is highly
      sensitive and allows quantification of the production of multiple cytokines by
      counting the percentage of positively staining cells.

PMID- 7504046
TI  - Refsum disease: a defect in the alpha-oxidation of phytanic acid in peroxisomes.
AB  - The oxidation of phytanic acid to pristanic acid was previously demonstrated to
      be deficient in monolayer cultures of skin fibroblasts (Herndon et al. 1969. J.
      Clin. Invest. 48: 1017-1032). However, identification of subcellular organelle
      with deficient enzyme activity has not been established. To define the
      subcellular organelle with deficient enzyme activity in the catabolism of
      phytanic acid, we measured the oxidation of [1-14C] phytanic acid to 14CO2 and
      pristanic acid in different subcellular organelles isolated from cultured skin
      fibroblasts from control and Refsum patients. The rates of oxidation of phytanic
      acid in peroxisomes, mitochondria, and endoplasmic reticulum were 37.1 +/- 2.65,
      1.9 +/- 0.3, and 0.4 +/- 0.07 pmol/h per mg protein, respectively, from control
      fibroblasts. The phytanic acid oxidation activity in mitochondria (2.04 +/- 0.7
      pmol/h per mg protein) and endoplasmic reticulum (0.43 +/- 0.2 pmol/h per mg
      protein) from Refsum fibroblasts was similar to control fibroblasts. However,
      phytanic acid oxidation in peroxisomes from Refsum fibroblasts was not detected
      at all the protein concentrations tested. On the other hand, the peroxisomes from
      Refsum fibroblasts had normal rates of activation and oxidation of palmitic and
      lignoceric acids, suggesting that the peroxisomes isolated from Refsum
      fibroblasts were metabolically active. The phytanoyl-CoA ligase, the first enzyme
      in the alpha-oxidation pathway, had activity similar to that in peroxisomes from
      control (9.86 +/- 0.09 nmol/h per mg protein) and Refsum (10.25 +/- 0.31 nmol/h
      per mg protein) fibroblasts. The data described here clearly demonstrate that
      pathognomonic accumulation of phytanic acid in patients with Refsum disease is
      due to the deficient activity of peroxisomal alpha-oxidation enzyme system.

PMID- 7504047
TI  - Purification of the major substrate for palmitoylation in rat adipocytes: N
      terminal homology with CD36 and evidence for cell surface acylation.
AB  - We previously reported that incubating rat adipocytes with [3H]palmitate
      predominantly labeled an 85-kDa protein. The labeling was more intensive in the
      presence of insulin and had characteristics consistent with covalent fatty
      acylation (Jochen et al. 1991. Biochem. Biophys. Res. Commun. 177: 797-801). In
      order to determine the significance of this finding we purified the 85-kDa
      protein, determined its N-terminal sequence, and further characterized its
      interactions with long-chain fatty acids. The [3H]palmitate-labeled 85-kDa
      protein was purified from rat adipocyte membranes using the following sequence of
      procedures: i) affinity chromatography with wheat germ agglutinin-agarose, ii)
      ion exchange chromatography with DEAE-Sepharose, and iii) SDS-polyacrylamide gel
      electrophoresis. The resulting labeled protein was sequenced through 30 amino
      acid residues. With the exception of one conserved substitution, the sequence was
      identical to CD36 (platelet membrane glycoprotein IV). Further characterization
      of the 85-kDa protein revealed it was heavily N-glycosylated and possessed a cell
      surface domain. Labeling of the 85-kDa protein with palmitate was compared in
      control cells, insulin-treated cells, and cells whose energy was depleted with
      2,4-dinitrophenol. Insulin and energy depletion increased labeling approximately
      3-fold and 12-fold, respectively. Labeling performed in the presence of energy
      depletion possessed all of the characteristics of covalent protein acylation. In
      addition, there was a close association between the ability of energy depletion
      to increase labeling of the 85-kDa protein and its ability to inhibit depletion
      of [3H]palmitate from the extracellular incubation media. These results suggest
      that the major substrate for fatty acylation in adipocytes is a cell surface
      membrane protein related to CD36 and that this acylation has the unusual
      properties of being independent of intracellular metabolic energy and of
      occurring on an exofacial epitope of the protein.

PMID- 7504048
TI  - Hepatitis C and B viruses, and their association with hepatocellular carcinoma in
      Egypt.
AB  - Hepatitis C and B viruses are associated with hepatocellular carcinoma in Europe,
      Asia and Southern Africa. A study of hepatitis C and hepatitis B virus infection
      was carried out on 70 patients with HCC, from the National Cancer Institute,
      Cairo University. Sera from patients were tested for anti-HCV and HBsAg markers.
      Twenty patients (30%) were anti HCV positive alone, 15 (21.4%) were HBsAg
      positive alone, 28 (40%) were positive for both anti-HCV and HBsAg and the
      remaining 6 patients (8.6%) were negative for the two markers. The total
      positivity for anti-HCV and for HBsAg in these patients was 70% and 61.4%
      respectively. The comparable figures in a recent study on 90 blood donors from
      Egypt, were 24.4% for anti-HCV and 4.4% for HBSAg. These data suggest a possible
      link between HCV and HBV infection and the development of hepatocellular
      carcinoma in Egypt, as has been found elsewhere in the world.

PMID- 7504049
TI  - Prevalence, impact and risk factors of hepatitis C infection.
AB  - The present study was designed to investigate the status of hepatitis C virus
      (HCV) infection and associated risk factors among Egyptian military recruits. The
      impact of HCV infection on liver function was also assessed. The sera of 726
      military recruits were tested for HCV antibodies using second generation ELISA
      technique (Ortho). The overall prevalence was 330.4%. Considering the presence of
      hepatitis B and/or schistosomiasis infection, HCV antibodies were detected in
      30.0% of HBsAg carriers, 36.8% of bilharzial patients and 48.8% of those with
      concomitant infections. Among individuals without schistosomiasis or HBV
      infection, the rate decreased to 22.5% positive with HCV. The present study
      indicated that parenteral exposure to the virus might be the most important route
      for acquiring infection, while blood transfusion had a very minor role. The study
      of the impact of HCV on liver functions revealed that a single infection with HCV
      only was associated with almost normal liver function tests. However, infection
      with more than one hepatitis virus revealed a greater impact on the liver
      function. Morbidity also increased when schistosomiasis infection was
      superimposed.

PMID- 7504050
TI  - Segment-specific modulation of the electrophysiological activity of leech Retzius
      neurons by acetylcholine.
AB  - 1. The acetylcholine responses of Retzius neurons were electrophysiologically and
      pharmacologically characterized in situ and in culture. Single-electrode voltage
      clamp was used to record currents from leech Retzius neurons from standard
      segments [Rz(X)] and from reproductive segments [Rz(5,6)]. 2. A 1 s pressure
      pulse of acetylcholine (ACh) produced a fast inward current followed by a slower
      outward current in Rz(X) neurons, whereas it produced only an outward current in
      Rz(5,6) neurons. These segment-specific responses were maintained when the two
      types of Retzius neurons were isolated in culture for up to 12 days. 3. The
      inward current of Rz(X) reversed at around -25 mV and was partially carried by
      Na+. This cationic current desensitized rapidly. The outward current of Rz(X) and
      Rz(5,6) neurons reversed at around -65 mV and was carried by Cl-. This anionic
      current desensitized very slowly upon prolonged applications of ACh. 4. The
      expression of the ACh-induced outward current in Rz(X) was season-dependent and
      was recorded in a larger proportion of Rz(X) neurons during the summer than
      during the winter. The expression of the ACh-induced outward current in Rz(5,6)
      did not show any seasonal pattern. 5. The fast inward current of Rz(X) was also
      elicited by nicotine; it was blocked by d-tubocurarine, hexamethonium and
      mecamylamine, but was not affected by alpha-bungarotoxin. The outward current of
      Rz(X) and Rz(5,6) was also elicited by nicotine and by 4-[N-(3
      chlorophenyl)carbamoxyloxy]2-butynyltrimethylammonium chloride (a muscarinic
      agonist); it was blocked by d-tubocurarine and by alpha-bungarotoxin, but it was
      not affected by hexamethonium or mecamylamine. 6. The results show that the
      serotonergic Retzius neurons of the leech could be tonically inhibited by ACh. In
      addition, the Retzius neurons from standard segments could also be phasically
      excited by ACh. The receptors responsible for the excitation fit into the
      classification of neuronal nicotinic receptors, whereas the receptors mediating
      the inhibition are closer in type to the muscular nicotinic receptor.

PMID- 7504051
TI  - Human natural killer cell committed thymocytes and their relation to the T cell
      lineage.
AB  - Recent studies have demonstrated that mature natural killer (NK) cells can be
      grown from human triple negative (TN; CD3-, CD4-, CD8-) thymocytes, suggesting
      that a common NK/T cell precursor exists within the thymus that can give rise to
      both NK cells and T cells under appropriate conditions. In the present study, we
      have investigated human fetal and postnatal thymus to determine whether NK cells
      and their precursors exist within this tissue and whether NK cells can be
      distinguished from T cell progenitors. Based on the surface expression of CD56
      (an NK cell-associated antigen) and CD5 (a T cell-associated antigen), three
      phenotypically distinctive populations of TN thymocytes were identified. CD56+,
      CD5-; CD56-, CD5-, and CD56-, CD5+. The CD56+, CD5- population of TN thymocytes,
      although displaying a low cytolytic function against NK sensitive tumor cell
      targets, were similar in antigenic phenotype to fetal liver NK cells, gave rise
      to NK cell clones, and were unable to generate T cells in mouse fetal thymic
      organ cultures (mFTOC). This population of thymocytes represents a relatively
      mature population of lineage-committed NK cells. The CD56-, CD5- population of TN
      thymocytes were similar to thymic NK cells in antigenic phenotype and NK cell
      clonogenic potential. Clones derived from this population of TN thymocytes
      acquired CD56 surface expression and NK cell cytolytic function. CD56-, CD5- TN
      thymocytes thus contain a novel population of NK cell-committed precursors. The
      CD56-, CD5- population of TN thymocytes also contains a small percentage of CD34+
      cells, which demonstrate no in vitro clonogenic potential, but possess T cell
      reconstituting capabilities in mFTOC. The majority of TN thymocytes do not
      express CD56, but coexpress CD34 and CD5. These CD56-, CD5+, CD34+ cells
      demonstrate no NK or T cell clonogenic potential, but are extremely efficient in
      repopulating mFTOC and differentiating into CD3+, CD4+, CD8+ T cells. The results
      of this investigation have identified NK cells and NK cell precursors in the
      human thymus and have shown that these cell types are unable to differentiate
      along the T cell lineage pathway. Thus, while a common NK/T cell progenitor
      likely exists, once committed to the NK cell lineage these cells no longer have
      the capacity to develop along the T cell developmental pathway.

PMID- 7504052
TI  - Regulation of thymocyte development through CD3. II. Expression of T cell
      receptor beta CD3 epsilon and maturation to the CD4+8+ stage are highly
      correlated in individual thymocytes.
AB  - Recent studies have shown that maturation of CD4-8- double negative (DN)
      thymocytes to the CD4+8+ double positive (DP) stage is dependent on expression of
      the T cell receptor (TCR)-beta polypeptide. The exact mechanism by which the TCR
      beta chain regulates this maturation step remains unknown. Previous experiments
      had suggested that in the presence of some TCR+ thymocytes, additional DN
      thymocytes not expressing a TCR-beta chain may be recruited to mature to the DP
      stage. The recent demonstration of an immature TCR-beta-CD3 complex on early
      thymocytes lead to the alternative hypothesis that signal transduction through an
      immature TCR-CD3 complex may induce maturation to the DP stage. In the latter
      case, maturation to the DP stage would depend on the expression of TCR-beta-CD3
      in the same cell. We examined these two hypotheses by studying the expression of
      the intra- and extracellular CD3 epsilon, CD3 zeta, and TCR-beta polypeptides in
      intrathymic subpopulations during embryogenesis. CD3 epsilon and CD3 zeta were
      expressed intracellularly 2 and 1 d, respectively, before intracellular
      expression of the TCR-beta chain, potentially allowing immediate surface
      expression of an immature TCR-beta-CD3 complex as soon as functional
      rearrangement of a TCR-beta gene locus has been accomplished. Calcium
      mobilization could be induced by stimulation with anti-CD3 epsilon mAb as soon as
      intracellular TCR-beta was detectable, suggesting that a functional TCR-beta-CD3
      complex is indeed expressed on the surface of early thymocytes. From day 17 on,
      most cells were in the DP stage, and over 95% of the DP cells expressed on the
      TCR-beta chain intracellularly. At day 19 of gestation, extremely low
      concentrations of TCR-beta chain and CD3 epsilon were detectable on the cell
      surface of nearly all thymocytes previously thought to be TCR-CD3 negative. These
      findings strongly support the hypothesis that maturation to the DP stage depends
      on surface expression of and subsequent signal transduction through an immature
      TCR-beta-CD3 complex and suggest that maturation to the DP stage by recruitment,
      if it occurs at all, is of minor relevance.

PMID- 7504053
TI  - Formation of eosinophilic and monocytic intradermal inflammatory sites in the dog
      by injection of human RANTES but not human monocyte chemoattractant protein 1,
      human macrophage inflammatory protein 1 alpha, or human interleukin 8.
AB  - Equilibrium binding studies on canine mononuclear and granulocytic cells allow
      the identification of a single high affinity receptor for the human C-C chemokine
      RANTES (dissociation constant, 14 +/- 8 pM), that, in contrast to the human
      RANTES receptor, has no affinity for human macrophage inflammatory protein 1
      alpha (hMIP-1 alpha). A single intradermal injection of hRANTES in dog resulted
      in eosinophil- and macrophage-rich inflammatory sites within 4 h. Cell
      infiltration peaked at 16-24 h after hRANTES injection. There was histological
      evidence of intravascular activation of eosinophils at 4 h, although eosinophils
      in the vasculature and interstitium contained apparently intact granules.
      Monocytes were the predominant cells adherent to venular endothelium at 16-24 h.
      Human MIP-1 alpha elicited no response in canine dermis, whereas monocyte
      chemoattractant protein 1 caused mild perivascular cuffing with monocytes. In
      contrast, human interleukin 8 induced a neutrophilic dermal infiltrate that was
      maximal by 4 h after challenge. This provides the first direct evidence in vivo
      that RANTES has significant proinflammatory activity and, in addition, could be a
      mediator in atopic pathologies characterized by eosinophilic and monocytic
      inflammatory responses.

PMID- 7504054
TI  - Developmental regulation of a mucinlike glycoprotein selectively expressed on
      natural killer cells.
AB  - Natural killer (NK) cells are CD3:TCR-, CD16+, CD56+ large granular lymphocytes
      capable of recognizing and eliminating a variety of virus-infected, malignant,
      and antibody-coated target cells. Two functionally distinct populations of
      peripheral blood NK cells can be differentiated by their surface expression of an
      isoform of the neural cell adhesion molecule (CD56). CD56bright NK cells have the
      attributes of an undifferentiated cell, in that they proliferate in response to
      exogenous cytokines, but exert poor cytolytic activity. CD56dim NK cells have the
      attributes of a more differentiated cell, in that they proliferate poorly in
      response to exogenous cytokines, but are potent cytolytic effector cells. Here we
      describe the molecular characterization of a NK cell restricted epitope (PEN5)
      that is selectively expressed on the functionally differentiated CD56dim NK
      cells. PEN5+ NK cells proliferate poorly in response to interleukin 2 (IL-2), but
      are potent cytolytic effectors, whereas PEN5- NK cells proliferate in response to
      IL-2, but are poor cytolytic effectors. Biochemical and immunochemical analyses
      reveal the PEN5 epitope to be an unusual sulfated poly-N-lactosamine carbohydrate
      related to keratan sulfate glycosaminoglycans. Immunoprecipitates prepared using
      a monoclonal antibody reactive with PEN5 include two polydisperse membrane-bound
      glycoproteins, PEN5 alpha (120-170 kD) and PEN5 beta (210-245 kD). Enzymatic
      deglycosylation reduces the apparent molecular weight of both PEN5 isoforms by 80
      90%, and classifies PEN5 beta as a mucinlike glycoprotein. The surface expression
      of the PEN5 epitope is downmodulated by stimuli that induce NK cell
      proliferation, and it is absent from leukemic NK cells of patients with granular
      lymphocyte proliferative disorder. Taken together, these results indicate that
      PEN5 is a developmentally regulated poly-N-lactosamine epitope associated with a
      mucin-type glycoprotein, whose expression is restricted to the population of
      nonproliferative NK cells fully committed to cytolytic effector function.

PMID- 7504055
TI  - Follicular dendritic cells help resting B cells to become effective antigen
      presenting cells: induction of B7/BB1 and upregulation of major
      histocompatibility complex class II molecules.
AB  - This study was designed to investigate whether follicular dendritic cells (FDC)
      can activate B cells to a state in which they can function as effective antigen
      presenting cells (APC). High buoyant density (i.e., resting) B cells specific for
      2,4-dinitro-fluorobenzene (DNP) were incubated with DNP-ovalbumin (OVA) bearing
      FDC, after which their capacity to process and present to an OVA-specific T cell
      clone was assessed. The efficacies of alternative sources of antigen and
      activation signals in the induction of B cell APC function were compared with
      those provided by FDC. Only FDC and Sepharose beads coated with anti
      immunoglobulin (Ig)kappa monoclonal antibody provided the necessary stimulus. FDC
      carrying inappropriate antigens also induced B cell APC function in the presence
      of exogenous DNP-OVA. However, in circumstances where soluble DNP-OVA was
      limiting, FDC bearing complexes containing DNP, which could crosslink B cell Ig
      receptors, induced the most potent APC function. Analysis by flow cytometry
      revealed that within 24 h of coculture with FDC, a significant percentage of B
      cells increased in size and expressed higher levels of major histocompatibility
      complex class II. By 48 h, an upregulation of the costimulatory molecule, B7/BB1,
      occurred, but only when exposed to the FDC bearing DNP. Taken together, the
      results demonstrate that FDC have the capacity to activate resting B cells to a
      state in which they can function as APC for T cells. The stimuli that FDC provide
      may include: (a) an antigen-dependent signal that influences the upregulation of
      B7/BB1; and (b) possibly a signal independent of crosslinking mIg that results in
      Ig internalization. The relevance of these findings to the formation of germinal
      centers and maintenance of the humoral response is discussed.

PMID- 7504056
TI  - High efficiency retroviral mediated gene transduction into single isolated
      immature and replatable CD34(3+) hematopoietic stem/progenitor cells from human
      umbilical cord blood.
AB  - Umbilical cord blood is rich in hematopoietic stem and progenitor cells and has
      recently been used successfully in the clinic as an alternative source of
      engrafting and marrow repopulating cells. With the likelihood that cord blood
      stem/progenitor cells will be used for gene therapy to correct genetic disorders,
      we evaluated if a TK-neo gene could be directly transduced in a stable manner
      into single isolated subsets of purified immature hematopoietic cells that
      demonstrate self-renewed ability as estimated by colony replating capacity.
      Sorted CD34(3+) cells from cord blood were prestimulated with erythropoietin
      (Epo), steel factor (SLF), interleukin (IL)-3, and granulocyte-macrophage colony
      stimulating factor (GM-CSF) and transduced with the gene in two ways. CD34(3+)
      cells were incubated with retroviral-containing supernatant from TK-neo vector
      producing cells, washed, and plated directly or resorted as CD34(3+) cells into
      single wells containing a single cell or 10 cells. Alternatively, CD34(3+) cells
      were sorted as a single cell/well and then incubated with viral supernatant.
      These cells were cultured with Epo, SLF, IL-3, and GM-CSF +/- G418. The TK-neo
      gene was introduced at very high efficiency into low numbers of or isolated
      single purified CD34(3+) immature hematopoietic cells without stromal cells as a
      source of virus or accessory cells. Proviral integration was detected in primary
      G418-resistant(R) colonies derived from single immature hematopoietic cells, and
      in cells from replated colonies derived from G418R-colony forming unit
      granulocyte erythroid macrophage megakaryocyte (CFU-GEMM) and -high proliferative
      potential colony forming cells (HPP-CFC). This demonstrates stable expression of
      the transduced gene into single purified stem/progenitor cells with replating
      capacity, results that should be applicable for future clinical studies that may
      utilize selected subsets of stem/progenitor cells for gene therapy.

PMID- 7504057
TI  - T cell receptor zeta/CD3-p59fyn(T)-associated p120/130 binds to the SH2 domain of
      p59fyn(T).
AB  - Intracellular signaling from the T cell receptor (TCR)zeta/CD3 complex is likely
      to be mediated by associated protein tyrosine kinases such as p59fyn(T), ZAP-70,
      and the CD4:p56lck and CD8:p56lck coreceptors. The nature of the signaling
      cascade initiated by these kinases, their specificities, and downstream targets
      remain to be elucidated. The TCR-zeta/CD3:p59fyn(T) complex has previously been
      noted to coprecipitate a 120/130-kD doublet (p120/130). This intracellular
      protein of unknown identity associates directly with p59fyn(T) within the
      receptor complex. In this study, we have shown that this interaction with
      p120/130 is specifically mediated by the SH2 domain (not the fyn-SH3 domain) of
      p59fyn(T). Further, based on the results of in vitro kinase assays, p120/130
      appears to be preferentially associated with p59fyn(T) in T cells, and not with
      p56lck. Antibody reprecipitation studies identified p120/130 as a previously
      described 130-kD substrate of pp60v-src whose function and structure is unknown.
      TCR-zeta/CD3 induced activation of T cells augmented the tyrosine phosphorylation
      of p120/130 in vivo as detected by antibody and GST:fyn-SH2 fusion proteins.
      p120/130 represents the first identified p59fyn(T):SH2 binding substrate in T
      cells, and as such is likely to play a key role in the early events of T cell
      activation.

PMID- 7504058
TI  - Short consensus repeat-3 domain of recombinant decay-accelerating factor is
      recognized by Escherichia coli recombinant Dr adhesin in a model of a cell-cell
      interaction.
AB  - A bacterial pathogen that is important in both urinary tract and intestinal
      infections is Escherichia coli which expresses Dr or related adhesins. In this
      report, we present a model for testing cell-cell interaction, using both
      molecularly characterized laboratory cells that express recombinant molecules of
      human decay-accelerating factor (DAF), and recombinant bacterial Dr colonization
      factors. Dr adhesin ligand was identified as DAF (CD55), a membrane protein that
      protects autologous tissues from damage due to the complement system. Structure
      function studies mapped the adhesin-binding site on the DAF molecule. A single
      point substitution in the third short consensus repeat domain, Ser165 to Leu,
      corresponding to the Dra to Drb allelic polymorphism, caused complete abolition
      of adhesin binding to DAF.

PMID- 7504059
TI  - Murine B7-2, an alternative CTLA4 counter-receptor that costimulates T cell
      proliferation and interleukin 2 production.
AB  - The B7-1 molecule, expressed on antigen presenting cells (APC), provides a
      crucial costimulatory signal for T cell activation. Recent studies demonstrate
      the existence of alternative, non-B7-1 CTLA4 counter-receptors in mice and
      humans. Here, we describe the molecular cloning and demonstrate costimulatory
      function of the murine B7-2 (mB7-2) gene. Murine B7-2 cDNA encodes a member of
      the Ig supergene family that binds CTLA4-Ig and stains with the GL1 but not anti
      mB7-1 mAb. Murine B7-2 costimulates the proliferation and interleukin 2
      production of CD4+ T cells and this costimulation can be inhibited by either
      CTLA4-Ig or GL1 mAb. Identification of the B7-2 molecule will permit further
      manipulation of the B7:CD28/CTLA4 costimulatory pathway which has been shown to
      be involved in the prevention of tolerance, induction of tumor immunity, and most
      recently, in the pathogenesis of autoimmunity.

PMID- 7504060
TI  - A critical role for monocytes and CD14 in endotoxin-induced endothelial cell
      activation.
AB  - Vascular endothelium activated by endotoxin (lipopolysaccharide [LPS]) and
      cytokines plays an important role in organ inflammation and blood leukocyte
      recruitment observed during sepsis. Endothelial cells can be activated by LPS
      directly, after its interaction with LPS-binding protein and soluble CD14 in
      plasma. LPS-LPS-binding protein complexes in blood also interact with monocytes
      and neutrophils bearing glycosyl-phosphatidylinositol (GPI) anchored membrane
      CD14 (mCD14), promoting the release of cytokines such as tumor necrosis factor
      and interleukin 1 (IL-1). These molecules, in turn, have the capacity to activate
      endothelial cells providing an indirect pathway for LPS-dependent endothelial
      cell activation. In this work, we address the relative importance of the direct
      and the indirect pathway of in vitro LPS-induced human umbilical vein endothelial
      cell (HUVEC) activation. Substituting whole blood for plasma resulted in a 1,000
      fold enhancement of HUVEC sensitivity to LPS. Both blood- and plasma-dependent
      enhanced activation of HUVEC were blocked with an anti-CD14 monoclonal antibody.
      Blood from patients with paroxysmal nocturnal hemoglobinuria, whose cells lack
      mCD14 and other GPI anchored proteins, was unable to enhance LPS activation of
      HUVEC above the level observed with plasma alone. IL-10, an inhibitor of monocyte
      release of cytokines, decreased the blood-dependent enhancement of HUVEC
      activation by LPS. Blood adapted to small doses of LPS was also less efficient
      than nonadapted blood in producing this enhancement. Addition of purified
      mononuclear cells to HUVEC or the transfer of plasma from whole blood incubated
      with LPS to HUVEC, duplicated the enhancement effect observed when whole blood
      was incubated with HUVEC. Taken together, these data suggest that the indirect
      pathway of LPS activation of endothelial cell is mediated by monocytes and mCD14
      through the secretion of a soluble mediator(s). The indirect pathway is far more
      efficient than the direct, plasma-dependent pathway.

PMID- 7504061
TI  - An interleukin 4 (IL-4) mutant protein inhibits both IL-4 or IL-13-induced human
      immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: support for
      a common component shared by IL-4 and IL-13 receptors.
AB  - Interleukin 4 (IL-4) and IL-13 share many biological functions. Both cytokines
      promote growth of activated human B cells and induce naive human surface
      immunoglobulin D+ (sIgD+) B cells to produce IgG4 and IgE. Here we show that a
      mutant form of human IL-4, in which the tyrosine residue at position 124 is
      replaced by aspartic acid (hIL-4.Y124D), specifically blocks IL-4 and IL-13
      induced proliferation of B cells costimulated by anti-CD40 mAbs in a dose
      dependent fashion. A mouse mutant IL-4 protein (mIL-4.Y119D), which antagonizes
      the biological activity of mouse IL-4, was ineffective. In addition, hIL-4.Y124D,
      at concentrations of up to 40 nM, did not affect IL-2-induced B cell
      proliferation. hIL-4.Y124D did not have detectable agonistic activity in these B
      cell proliferation assays. Interestingly, hIL-4.Y124D also strongly inhibited
      both IL-4 or IL-13-induced IgG4 and IgE synthesis in cultures of peripheral blood
      mononuclear cells, or highly purified sIgD+ B cells cultured in the presence of
      anti-CD40 mAbs. IL-4 and IL-13-induced IgE responses were inhibited > 95% at a
      approximately 50- or approximately 20-fold excess of hIL-4.Y124D, respectively,
      despite the fact that the IL-4 mutant protein had a weak agonistic activity. This
      agonistic activity was 1.6 +/- 1.9% (n = 4) of the maximal IgE responses induced
      by saturating concentrations of IL-4. Taken together, these data indicate that
      there are commonalities between the IL-4 and IL-13 receptor. In addition, since
      hIL-4.Y124D inhibited both IL-4 and IL-13-induced IgE synthesis, it is likely
      that antagonistic mutant IL-4 proteins may have potential clinical use in the
      treatment of IgE-mediated allergic diseases.

PMID- 7504062
TI  - Fas transduces activation signals in normal human T lymphocytes.
AB  - The Fas gene encodes a cell surface molecule that is a member of the the nerve
      growth factor/tumor necrosis factor receptor family of proteins and can mediate
      programmed cell death (apoptosis) in certain transformed cell lines. To
      characterize further the biological function of Fas, particularly with regard to
      its function in normal cells, a panel of monoclonal antibodies (mAbs) was
      generated against the extracellular portion of human Fas. Some of these mAbs
      induced apoptosis in transformed cell lines expressing Fas, but only when
      immobilized on the culture vessel. One of the new Fas mAbs (M38) was used for
      studies on normal lymphoid cells and found to stimulate the proliferation of
      purified human T cells and thymocytes when immobilized on culture wells along
      with CD3 antibody. T cell proliferation induced by Fas mAb was largely
      interleukin 2 independent and was demonstrated to be due to a direct effect on
      the precursor T cell. Thus, the data demonstrate that in addition to a role in
      the induction of apoptosis in certain transformed cell lines, the Fas protein may
      also play an important role in the activation and proliferation of normal T
      cells.

PMID- 7504063
TI  - Autoantibodies from patients with primary biliary cirrhosis recognize a
      restricted region within the cytoplasmic tail of nuclear pore membrane
      glycoprotein Gp210.
AB  - Patients with primary biliary cirrhosis (PBC) frequently have autoantibodies
      against a 210-kD integral glycoprotein of the nuclear envelope pore membrane.
      This protein, termed gp210, has a 1,783-amino acid amino-terminal domain located
      in the perinuclear space, a 20-amino acid transmembrane segment, and a 58-amino
      acid cytoplasmic carboxy-terminal tail. We now demonstrate that autoantibodies
      from 25 patients with PBC that recognize gp210 react with the cytoplasmic carboxy
      terminal tail while none react with unmodified linear epitopes in the amino
      terminal domain. The epitope(s) recognized by autoantibodies from all 25 patients
      is contained within a stretch of 15 amino acids. The recognized amino acid
      sequence is homologous to the protein products of the Escherichia coli mutY gene
      and Salmonella typhimurium mutB gene with an exact identity of six consecutive
      amino acids, suggesting that anti-gp210 antibodies may arise by molecular mimicry
      of bacterial antigenic determinants.

PMID- 7504064
TI  - An essential role for interferon gamma in resistance to Mycobacterium
      tuberculosis infection.
AB  - Tuberculosis, a major health problem in developing countries, has reemerged in
      recent years in many industrialized countries. The increased susceptibility of
      immunocompromised individuals to tuberculosis, and many experimental studies
      indicate that T cell-mediated immunity plays an important role in resistance. The
      lymphokine interferon gamma (IFN-gamma) is thought to be a principal mediator of
      macrophage activation and resistance to intracellular pathogens. Mice have been
      developed which fail to produce IFN-gamma (gko), because of a targeted disruption
      of the gene for IFN-gamma. Upon infection with Mycobacterium tuberculosis,
      although they develop granulomas, gko mice fail to produce reactive nitrogen
      intermediates and are unable to restrict the growth of the bacilli. In contrast
      to control mice, gko mice exhibit heightened tissue necrosis and succumb to a
      rapid and fatal course of tuberculosis that could be delayed, but not prevented,
      by treatment with exogenous recombinant IFN-gamma.

PMID- 7504065
TI  - Two uncomfortable stories of dying.

PMID- 7504067
TI  - Physiological and genetic regulation of rRNA synthesis in Lactococcus.
AB  - The macromolecular composition of Lactococcus was regulated by growth rate in the
      same general way as that of less fastidious bacteria such as Escherichia coli and
      Salmonella typhimurium. The ratios of RNA:DNA and RNA:protein increased
      approximately threefold over a 13.5-fold increase in growth rate, whereas the
      ratio of DNA:protein remained approximately constant. Using reporter genes fused
      to a DNA fragment of a cloned lactococcal rRNA operon, promoter activity was
      located upstream of the 16S rRNA structural gene. This DNA fragment had some
      characteristics typical of a rrn promoter in E. coli. Two consensus promoter
      sequences P1 and P2 were located 296 and 157 bp, respectively, upstream of the
      start of the 16S rRNA gene. Between P2 and the start of the 16S rRNA gene,
      sequences were identified with typical anti-termination motifs characteristic of
      E. coli rrn promoter regions. A putative transcription terminator sequence was
      identified downstream of the 5S rRNA gene and putative primary RNA transcript
      processing sites at both ends of the lactococcal rRNA operon were also noted.

PMID- 7504066
TI  - Iron-regulated salicylate synthesis by Pseudomonas spp.
AB  - Two iron-regulated compounds have been found in acidified ethyl acetate extracts
      from culture supernatants of Pseudomonas aeruginosa and Pseudomonas cepacia type
      strains. Synthesis of both compounds paralleled iron-deficient growth, and was
      repressed in the presence of 100 microM-FeCl3. Yields of these substances varied
      among different strains and attained maximum levels during stationary phase. Thin
      layer chromatographic analysis in five different solvent systems revealed that
      the slower-moving compound chromatographed as two distinct bands, and showed RF
      values and spectral properties similar to pyochelin. The faster-moving compound
      co-migrated as a single band with a standard of commercial salicylic acid in each
      of the chromatographic systems tested. Moreover, a molecule with an identical RF
      was also produced by Pseudomonas fluorescens CHA401, which is known to synthesize
      salicylic acid as the only siderophore during iron-limited growth.
      Spectrophotometric and spectrofluorometric titrations led to the identification
      of this iron-regulated compound as salicylic acid, in agreement with the
      structure deduced from 1H-NMR and mass spectroscopy. The identity of the P.
      cepacia siderophore azurechelin as salicylic acid was also conclusively
      demonstrated. Salicylic acid, like pyochelin and pyoverdin, promoted P.
      aeruginosa growth in an iron-depleted medium. These results are consistent with a
      putative siderophore activity for salicylic acid, i.e. azurechelin, as has been
      demonstrated for P. aeruginosa, P. fluorescens and P. cepacia. Thus, salicylic
      acid is likely to act as a siderophore in more than one species belonging to the
      genus Pseudomonas.

PMID- 7504068
TI  - Metabolism of polysaccharides by the Streptococcus mutants dexB gene product.
AB  - The Streptococcus mutans dexB gene, a member of the multiple sugar metabolism
      (msm) operon, encodes an intracellular glucan 1,6-alpha-glucosidase which
      releases glucose from the non-reducing terminus of alpha-1,6-linked
      isomaltosaccharides and dextran. Comparison of primary amino acid sequences
      showed strong homology to Bacillus oligo-1,6-glucosidases and, like these
      enzymes, DexB was able to release free glucose from the alpha-1,4,6-branch point
      in panose. This suggested a role for DexB in the metabolism of either starch or
      intracellular polysaccharide, which contain such branch points. However, purified
      intracellular polysaccharide from the wild-type S. mutans strain LT11 and a
      mutant deficient in dexB revealed no substantial differences in the extent of
      branching as demonstrated by iodine staining spectra and the degree of
      polymerization. Furthermore, thin layer chromatography of radiolabelled
      intracellular polysaccharide digested with S. mutans wild-type and mutant cell
      extracts showed no differences in the products obtained. The involvement of DexB
      in dietary starch metabolism was investigated using alpha-limit dextrins produced
      from the action of alpha-amylase on starch. These induced the msm operon,
      including dexB, and the DexB enzyme was able to act on the alpha-limit dextrins
      to give further fermentable substrates. The transport system encoded by the msm
      operon can also transport alpha-limit dextrin. DexB may therefore be important in
      the metabolism of extracellular starch.

PMID- 7504069
TI  - Haemin-binding proteins of Porphyromonas gingivalis W50 grown in a chemostat
      under haemin-limitation.
AB  - Porphyromonas gingivalis W50 was grown in a chemostat at pH 7.3 under haemin
      limitation and haemin-excess at a constant mean doubling time of 6.9 h. Outer
      membranes (OM) were extracted from whole cells using EDTA and compared by SDS
      PAGE. Haemin-limited cells expressed novel outer membrane proteins (OMPs) of mol.
      mass 115, 113 and 19 kDa when samples were solubilized at 100 degrees C. A 46 kDa
      OMP was observed in haemin-excess cells but not in those from haemin-limited
      conditions. Tetramethylbenzidine (TMBZ) staining of gels, after OM solubilization
      at 20 degrees C, was used to detect haemin-binding proteins (HBPs). HBPs were
      observed only in OM from haemin-limited cells. The major HBP (mol. mass 32.4 kDa)
      corresponded to a similar sized Kenacid-blue-stained protein which was not
      observed in haemin-excess-derived OM. Haemin-limited cells and OM displayed a
      ladder-like series of Kenacid-blue-stained proteins. Lighter TMBZ-stained
      proteins of mol. mass 51, 53, 56 and 60 kDa, with mobilities corresponding to
      those of silver-stained LPS components, were observed in haemin-limited OM. No
      soluble HBPs were detected extracellularly. The greater number of HBPs expressed
      by cells grown under haemin-limitation may reflect an additional cell surface
      receptor system for haemin acquisition under low environmental levels of this
      essential cofactor.

PMID- 7504070
TI  - Ultrastructure of proteinase-secreting cells of Candida albicans studied by
      alkaline bismuth staining and immunocytochemistry.
AB  - The ultrastructure of Candida albicans cells induced to secrete extracellular
      proteinase (EPR) has been studied. Electron microscopy employing alkaline bismuth
      staining, a method which stains polysaccharides, clearly revealed Golgi-like
      bodies and secretory vesicles in C. albicans cells. After EPR induction, there
      was no apparent increase in the number of these structures. Instead, many
      flocculent granules appeared at the periphery of induced cells. The granules were
      similar to secretory vesicles in size, but were more irregular in shape. Similar
      granules were observed in non-induced cells, though less frequently than in
      induced cells. Brefeldin A, a specific inhibitor of membrane transport in the
      secretory pathway, caused the accumulation of EPR and Golgi-like bodies in EPR
      induced cells, but did not affect the accumulation of the granules. These results
      suggest that the granules are unrelated to EPR secretion. Electron microscope
      immunocytochemistry with affinity-purified anti-EPR antibodies showed that the
      granules in EPR-induced cells were recognized by the antibodies. This recognition
      was completely inhibited by the presence of glycogen, suggesting that antibodies
      cross-react with glycogen-like polysaccharides in the granules. Although the
      location of EPR within the cells remains unclear, the results suggest that EPR
      might be secreted via the constitutive secretory pathway, and that EPR is
      glycosylated to give a structure with some similarity to glycogen.

PMID- 7504071
TI  - Induction of programmed cell death (apoptosis) by influenza virus infection in
      tissue culture cells.
AB  - The process of cell death caused by influenza virus infection in cultured MDCK
      and HeLa cells was analysed. This infection gave rise to nuclear fragmentation
      and chromatin condensation accompanied by chromosomal DNA fragmentation into
      oligonucleosomes. Chromosomal DNA fragmentation progressed concomitantly with
      cell lysis of MDCK cells and HeLa cells, producing high and low yields of virus
      particles, respectively, indicating that the extent of cell lysis was not
      proportional to the virus production. The endonuclease inhibitor zinc blocked DNA
      fragmentation in MDCK cells. Cycloheximide inhibited DNA fragmentation as well as
      cell lysis. Inhibition occurred when the drug was added to the medium within 2 h
      after infection but not efficiently at 4 h or later. Infection induced the Fas Ag
      gene, which encodes a possible apoptosis-mediating molecule, in the early
      infectious stage followed by the expression of Fas Ag on the cell surface. These
      results suggested that influenza virus infection causes apoptotic death of
      cultured cells, and their fate might be determined at an early stage of the
      infection by induction of an apoptotic gene.

PMID- 7504072
TI  - Measles virus antigens induce both type-specific and canine distemper virus cross
      reactive cytotoxic T lymphocytes in mice: localization of a common Ld-restricted
      nucleoprotein epitope.
AB  - We have studied the induction of the cytotoxic T lymphocyte (CTL) response to
      measles virus (MV) antigens expressed as vaccinia virus (VV) recombinants in a
      murine model. In C3H mice (H-2k) only the nucleoprotein (NP) induced a CTL
      response and this was shown to be cross-reactive with the closely related canine
      distemper virus (CDV). The presentation of this antigen was shown to be Kk
      restricted. In BALB/c mice (H-2d), both the haemagglutinin (HA) and the NP
      induced a strong CTL response, the former being serotype-specific, whereas the
      latter cross-reacted with CDV. Both responses were found to be Ld-restricted.
      Based on the prediction for Ld T cell motifs, we tested a number of MV NP-derived
      nonapeptides for their capacity to sensitize P815 cells (H-2d) for lysis by
      spleen cells from VV-NP-immunized mice. One of these peptides, comprising amino
      acids 281 to 289 (Tyr-Pro-Ala-Leu-Gly-Leu-His-Glu-Phe) was as effective as cells
      expressing the complete NP protein. This motif is conserved in the CDV NP.

PMID- 7504073
TI  - Characterization of the genomic sequence of type V (or 3a) hepatitis C virus
      isolates and PCR primers for specific detection.
AB  - We have identified four new hepatitis C virus (HCV) isolates whose genomic RNA
      could be amplified by PCR using primers from the 5' untranslated region (UTR),
      but the RNA could not be detected with genotype I to IV (or types 1a, 1b, 2a and
      2b respectively)-specific core region-derived primers. We compared the nucleotide
      sequences of the new isolates from positions 65 to 1850 (3' end of 5' UTR, C, E1
      and 5' end of E2/NS1) and 8276 to 9394 (3' end of NS5 and 3' UTR) with those for
      genotypes I to IV. The four isolates had the following characteristics: (i) the
      overall nucleotide sequence similarity between the four isolates was 95 to 96%,
      compared to 73 to 74%, 73%, 70% or 69 to 70% against genotypes I, II, III or IV,
      respectively; (ii) the sequence similarity to other reported 'type V (3a)'
      isolates was 88 to 100%; (iii) the hypervariable region 1 [(HVR)-1] was present
      but HVR-2 was absent within the E2/NS1 region; (iv) only one in-frame termination
      codon was present for the presumed polyprotein; (v) the 3'UTR preceding a
      terminal poly(U) stretch was significantly shorter than in genotype I to IV
      isolates. We classified the four isolates as genotype V (3a), and searched for
      uniquely conserved nucleotide sequences that could be used for type-specific PCR.
      A core region-derived primer pair (no. 104V: 5' CGTAAAACTTCT GAACGGTC, sense and
      no. 339: 5' GCTGAGCCCA GGACCGGTCT, antisense) was identified and successfully
      used to diagnose genotype V (3a) HCV infection.

PMID- 7504074
TI  - Sequence variation within neutralizing epitopes of the envelope glycoprotein B of
      human cytomegalovirus: comparison of isolates from renal transplant recipients
      and AIDS patients.
AB  - The envelope glycoprotein B of human cytomegalovirus (CMV) is a major target of
      the neutralizing antibody response against this virus, and hence has importance
      as a potential subunit vaccine. PCR was utilized to amplify DNA encoding the
      dominant antigenic determinant on this molecule, AD-1 (codons 552 to 635), and
      DNA sequencing was carried out in order to compare nucleotide variation in AD-1
      between clinical isolates of CMV and the laboratory strain AD169. Wild-type CMV
      strains isolated from AIDS patients were not only more likely to possess
      nucleotide substitutions (19/24 compared to 5/25, P < 0.0001) than those from
      renal transplant recipients, but they also exhibited a greater degree of
      nucleotide sequence divergence (6.94 versus 0.82 substitutions/1000 bp, P <
      0.0001; 96.0 to 100% versus 99.4 to 100% similarity). Increased sequence
      variation in the AIDS patients did not correlate with absolute peripheral blood
      CD4+ T cell level (r = 0.33, P > 0.1). Only two strains from AIDS patients and
      one strain from the renal transplant recipients possessed nucleic acid
      substitutions that resulted in codon changes, indicating that AD-1 is relatively
      well conserved amongst clinical isolates of CMV. The demonstration of strains
      with codon changes within neutralizing epitopes, however, highlights the
      importance of taking into consideration the presence of these strains within the
      wild-type virus population when preparing subunit vaccines.

PMID- 7504075
TI  - Analysis of feline calicivirus capsid protein genes: identification of variable
      antigenic determinant regions of the protein.
AB  - Three isolates of feline calicivirus (FCV) designated NADC, KCD and CFI/68 were
      compared for biochemical, serological and genetic variation within the capsid
      protein gene. The M(r) of the capsid protein from purified virions was
      approximately 66,000 for the NADC virus isolate, which differed slightly from the
      relative mobilities of the purified capsid proteins of the KCD and CFI/68
      isolates. Polyclonal antisera from either cats infected or rabbits hyperimmunized
      with the CFI/68 isolate cross-reacted with all three isolates by Western blot
      analysis. However, these polyclonal antisera to CFI/68 varied considerably in
      their virus-neutralization titres to the KCD and NADC isolates. Nucleotide
      sequence data confirmed the genetic variability among these FCV isolates.
      Comparison of the predicted amino acid sequence of the capsid protein among
      isolates revealed two regions of sequence divergence that probably contain the
      antigenically variable determinants. These hypervariable regions may vary by as
      much as 55% among isolates of FCV. The amino acid sequence diversity in the
      hypervariable regions of the KCD and NADC isolates correlated well with the virus
      neutralization data and suggests that polyvalent vaccines may be more protective
      than the commonly used monovalent vaccines.

PMID- 7504076
TI  - A 29K envelope glycoprotein of equine arteritis virus expresses neutralization
      determinants recognized by murine monoclonal antibodies.
AB  - A panel of six neutralizing murine monoclonal antibodies (MAbs) to equine
      arteritis virus (EAV) was produced. The MAbs were characterized by Western
      immunoblotting assay and competitive ELISA. The six MAbs identify a single
      neutralization site on a 29K envelope glycoprotein. Deglycosylation of viral
      proteins prior to immunoblotting showed that the 29K protein is the glycosylated
      form of a 20K protein. Equine anti-EAV serum also strongly bound the 29K
      glycoprotein, as well as an unglycosylated protein of 17K. The equine antisera to
      EAV blocked the binding of a selected MAb to EAV, whereas normal equine serum did
      not. Two neutralization-resistant escape mutant (EM) variants of the EAV
      prototype were produced using MAb 6D10. The phenotypic properties of the EM
      viruses were characterized by neutralization and immunoblotting assays with two
      MAbs (6D10 and 5G11). The two MAbs failed to neutralize either EM virus, and they
      did not react in an immunoblot assay with any proteins of the EM viruses. In
      contrast, binding of the equine antiserum to viral proteins was equivalent with
      prototype and EM virus strains. These data clearly indicate that a 29K envelope
      glycoprotein expresses at least one neutralization determinant of EAV.

PMID- 7504077
TI  - Resistance to temephos, an organophosphorous insecticide, in Culex pipiens from
      Tunisia, North Africa.
AB  - Resistance to temephos, an organophosphorous insecticide (OP), was found to be
      low (2-fold) in 2 Culex pipiens populations collected in Sayada (mid-eastern
      Tunisia). This resistance was synergized by an esterase inhibitor (DEF). Two sets
      of over-produced esterases (A2-B2 and A4-B4), known to be involved in resistance,
      were identified in almost 50% of the examined insects. In addition, 3% of insects
      had an insensitive acetylcholinesterase. After selecting larvae of one of the
      samples (ES) with temephos for 6 generations, a 9-fold increase in resistance was
      observed, and all mosquitoes were found to carry esterases A2-B2 and an
      insensitive acetylcholinesterase. These results must be considered in future
      mosquito control programs, since 2 of the identified genes can lead to high
      resistance to several organophosphorous insecticides.

PMID- 7504078
TI  - Myelin P0-glycoprotein: predicted structure and interactions of extracellular
      domain.
AB  - Protein zero (P0), a transmembrane glycoprotein, accounts for over 50% of the
      total protein in PNS myelin. The extracellular domain of P0 (P0-ED) is similar to
      the immunoglobulin variable domain, carrying one acceptor sequence for N-linked
      glycosylation. The x-ray diffraction analysis of PNS myelin has demonstrated
      reversible transitions that depend on pH and ionic strength, resulting in three
      distinct structures characterized by widths of about 36 A, 50 A (native), and 90
      A between the extracellular surfaces of the membranes. In the current work, we
      considered the constraints imposed by these x-ray diffraction data on the
      orientation of P0-ED, and we propose how this immunoglobulin-like domain could be
      accommodated in the variable widths of the extracellular space between myelin
      membranes. The modeling made use of the finding that beta-strand predictions for
      P0-ED are virtually superimposable with those of the VH domain of the
      phosphocholine-binding immunoglobulin M603 of mouse, which has a similar number
      of residues as P0-ED and a structure that has been solved crystallographically.
      The dimensions of P0-ED from the space-filling model, developed using PC-based
      molecular modeling software, were found to be 44 A x 25 A x 23 A. On the
      assumption that neither the shape nor the orientation of P0-ED changes
      appreciably, then the different widths at the extracellular apposition would
      easily accommodate P0-ED from apposed membranes if the molecules were oriented so
      that the beta-strands were approximately perpendicular to the membrane
      surface.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504079
TI  - Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical
      impact model.
AB  - Using a controlled cortical impact model of traumatic brain injury (TBI) coupled
      with tissue microdialysis, interstitial concentrations of aspartate and glutamate
      (together with serine and glutamine) were assessed in rat frontal cortex.
      Histological analysis indicated that the severity of injury following severe TBI
      (depth of deformation = 3.5 mm) was approximately twice that occurring following
      moderate TBI (depth of deformation = 1.5 mm). Both groups demonstrated
      significant postinjury maximal increases in excitatory amino acid (EAA)
      concentration, which were proportional to the severity of injury. The mean +/-
      SEM fold increase in dialysate concentrations of aspartate was 38 +/- 13 (n = 5)
      for moderate TBI and 74 +/- 12 (n = 5) for severe TBI. Fold increases in
      glutamate concentrations were 81 +/- 26 and 144 +/- 23 for moderate and severe
      TBI, respectively. Although these increases normalized within 20-30 min following
      moderate TBI, concentrations of aspartate and glutamate took > 60 min to
      normalize after severe TBI. Changes in levels of nontransmitter amino acids were
      much smaller. Fold increases for serine concentrations were 4.6 +/- 0.6 and 7.6
      +/- 1.7 in moderate and severe TBI, respectively; glutamine concentrations had
      similar small fold increases (2.6 +/- 0.2 and 4.1 +/- 0.6, respectively).
      Calculation of interstitial concentrations following severe TBI indicated that
      aspartate and glutamate maximally increased to 123 +/- 20 and 414 +/- 66 microM,
      respectively. To determine the extent to which such tissue concentrations of EAAs
      could contribute to the injury seen in TBI, the EAA receptor agonists N-methyl-D
      aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid were
      slowly injected into rat cortex. Remarkably similar histological injuries were
      produced by this procedure, supporting the notion that TBI is an excitotoxic
      injury.

PMID- 7504080
TI  - Inhibition of glutamate uptake with L-trans-pyrrolidine-2,4-dicarboxylate
      potentiates glutamate toxicity in primary hippocampal cultures.
AB  - Sodium-dependent, high-affinity glutamate transport is generally assumed to limit
      the toxicity of glutamate in vivo and in vitro, but there is very little direct
      evidence to support this hypothesis. In the present study, the effects of the
      specific uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylate on the toxicity
      and clearance of glutamate were examined in hippocampal neuronal cultures. At a
      concentration that was not toxic by itself, L-trans-pyrrolidine-2,4-dicarboxylate
      increased the toxicity of glutamate approximately fivefold and slowed the
      clearance of glutamate from the extracellular space. This toxicity was almost
      completely blocked by the N-methyl-D-aspartate receptor antagonist, D-2-amino-5
      phosphonopentanoate. These studies provide direct evidence that sodium-dependent,
      high-affinity glutamate transport limits glutamate toxicity in vitro.

PMID- 7504081
TI  - A neurofilament-associated kinase phosphorylates only a subset of sites in the
      tail of chicken midsize neurofilament protein.
AB  - Although neurofilaments are among the most highly phosphorylated proteins extant,
      relatively little is known about the kinases involved in their phosphorylation.
      The majority of the phosphates present on the two higher-molecular-mass
      neurofilament subunits are added to multiply repeated sequence motifs in the
      tail. We have examined the specificity of a neurofilament-associated kinase
      (NFAK) partially purified from chicken spinal cord that selectively
      phosphorylates the middle-molecular-mass neurofilament subunit, NF-M. Two
      dimensional phosphopeptide mapping of 32P-labeled NF-M shows that, in vitro, NFAK
      phosphorylates a subset of peptides phosphorylated in vivo in cultured neurons.
      The absence of a complete complement of labeled phosphopeptides following in
      vitro phosphorylation, compared with phosphorylation in vivo, is not due to a
      lack of availability of phosphorylation sites because the same maps are obtained
      when enzymatically dephosphorylated NF-M is used as an in vitro substrate.
      Phosphopeptide maps from in vitro-phosphorylated NF-M and those from a
      recombinant fusion protein containing only a segment of the tail piece of chicken
      NF-M reveal identical labeled peptides. The fusion protein lacks a segment
      containing 17 KXX(S/T)P putative phosphorylation sites contained in the tail of
      chicken NF-M but contains a segment that includes four KSPs and a KSD site also
      present in the intact tail. These results suggest (a) that NFAK mediates the
      phosphorylation of some, but not all, potential phosphorylation sites within the
      tail of NF-M and (b) that multiple kinases are necessary for complete
      phosphorylation of the NF-M tail.

PMID- 7504082
TI  - Epitope mapping of form-specific and nonspecific antibodies to
      acetylcholinesterase.
AB  - We have mapped the epitopes to which two monoclonal antibodies against
      acetylcholinesterase (AChE) from Torpedo californica are directed. One antibody,
      2C9, has equivalent affinity for both the 5.6S (amphiphilic) and 11S
      (hydrophilic) enzyme forms; the other, 4E7, recognizes only the amphiphilic form
      and has been shown previously to require an N-linked oligosaccharide residue on
      the protein. Isolation of cyanogen bromide peptides from the amphiphilic form and
      assay by a competition ELISA for 2C9 and by a direct binding ELISA for 4E7
      identified the same peptide, residues 44-82, as containing epitopes against both
      antibodies. The epitope for 4E7 includes the oligosaccharide conjugated to Asp59,
      an N-linked glycosylation site not present in mouse AChE. A 20-amino-acid
      synthetic peptide, RFRRPEPKKPWSGVWNASTY, representing residues 44-63, was
      synthesized and found to inhibit completely 2C9 binding to 5.6S enzyme at molar
      concentrations comparable to those of the cyanogen bromide peptide. It was
      unreactive with 4E7. Fractionation of the synthetic peptide further localized the
      2C9 epitope. Peptides RFRRPEPKKPW and KPWSGVWNASTY both reacted but less so than
      the entire synthetic peptide at equivalent molar concentrations, whereas the
      peptide RPEPKKPWSGVWNASTY was as effective as the larger synthetic peptide. The
      crystal structure of AChE shows the peptide to be on the surface of the molecule
      as part of a convex hairpin loop starting before the first alpha-helix.

PMID- 7504083
TI  - Growth conditions differentially regulate the expression of alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionate (AMPA) receptor subunits in cultured neurons.
AB  - We have studied the expression of alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA) receptor subunits in cultured cerebellar granule cells [7 days
      in vitro (DIV)] grown in medium containing different concentrations of K+ (10,
      25, or 40 mM) with or without 100 microM N-methyl-D-aspartate (NMDA; added once
      after 2 DIV). All these conditions are known to influence maturation and survival
      of granule cells, as well as the functional expression of NMDA receptors during
      development in culture. The expression of both glutamate receptor (GluR) subunit
      1 mRNA and receptor protein was low in cultures grown in 10 mM K+ (K10) and
      increased dramatically in cultures grown in 25 mM K+ (K25), with intermediate
      levels found in cultures grown in K10 and chronically exposed to NMDA (K10 +
      NMDA). In cultures grown in 40 mM K+ (K40), the expression of GluR1 mRNA and
      receptor protein was lower than in K25 but still higher than in K10. GluR2 and -3
      subunits were differently regulated by growth conditions, with their expression
      being higher in K10 and progressively reduced to the lowest levels in K40 (both
      mRNA and receptor proteins). GluR4 mRNA levels did not differ between K10 and
      K25, although they were reduced by chronic exposure to NMDA. To test how the
      differential expression of the various subunits affects the functional activity
      of AMPA receptors, we have measured AMPA-stimulated 45Ca2+ influx and 4 beta
      [3H]phorbol 12,13-dibutyrate binding in intact cells. Both functional parameters
      increased along with the K+ concentration and were maximal in K40, in coincidence
      with the lowest expression of the GluR2 subunits.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7504084
TI  - Differential processing of the ferritin heavy chain mRNA in human liver and adult
      human brain.
AB  - Northern blot analyses of the poly(A)+ RNAs from human brain and liver, using a
      human brain ferritin heavy chain (FTH) cDNA as the probe, shows the presence of
      two transcripts of 1.4 and 1.1 kb. The larger, 1.4-kb RNA, is expressed
      predominantly in the brain, whereas the smaller, 1.1 kb, is expressed abundantly
      in the liver. Screening of two normal human brain cDNA libraries yielded two
      types of human brain FTH cDNAs. One type corresponds to the previously
      characterized 1.1-kb RNA from liver and lymphocytes. The other is also identical
      to the previously characterized FTH cDNA except that it contains an additional
      279-bp sequence at the 3' untranslated region. This additional sequence shows
      94.1%, 62.5%, and 58.9% identity to the 3' flanking sequence of the human liver
      and mouse and rat FTH genomic clones, respectively. A fragment of a genomic clone
      containing the 279-bp sequence was also isolated and sequenced. These data
      suggest that differential processing of the primary transcript for the FTH mRNA
      in human brain and liver could generate two mature mRNAs of 1.4 and 1.1 kb. This
      could be due to the use of alternative polyadenylation sites in the pre-mRNA.

PMID- 7504085
TI  - Plasma 5-hydroxyindoleacetic acid as an indicator of monoamine oxidase-A
      inhibition in rat brain and peripheral tissues.
AB  - We have examined the changes induced by the monoamine oxidase (MAO; EC 1.4.3.4)
      inhibitors tranylcypromine, clorgyline, and deprenyl on MAO activity and 5
      hydroxytryptamine (serotonin, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)
      content in rat brain and blood (plasma and whole blood). The decreases of MAO-A
      activity observed in the liver and lungs after different doses of clorgyline or
      tranylcypromine correlated significantly (r > 0.80 in all cases) with the decline
      of plasma 5-HIAA. This was unaffected by 0.25 and 5 mg kg-1 of deprenyl,
      indicating that 5-HT was deaminated exclusively in the periphery by MAO-A. It is
      interesting that very potent and significant correlations (r > 0.75) were found
      between plasma 5-HIAA and MAO-A activity, 5-HIAA and 5-HT content in brain
      tissue. These results suggest that plasma 5-HIAA can be used confidently as a
      peripheral indicator of the inhibition of MAO-A in brain. This may represent a
      favorable alternative to the analysis of 5-HIAA in CSF in psychiatric patients
      undergoing antidepressant treatment with nonspecific MAO inhibitors or with the
      new selective MAO-A inhibitors.

PMID- 7504086
TI  - 1,2,3,4-Tetrahydro-2-methyl-4,6,7-isoquinolinetriol depletes catecholamines in
      rat brain.
AB  - 1,2,3,4-Tetrahydro-2-methyl-4,6,7-isoquinolinetriol (TMIQ) was synthesised and
      tested for activity as a dopamine-depleting agent in rat brain. After
      intracerebroventricular infusion, TMIQ caused reductions in dopamine
      concentrations in substantia nigra, striatum, hypothalamus, and dorsal raphe, and
      reduction in noradrenaline concentrations in locus coeruleus. TMIQ also reduced 5
      hydroxytryptamine concentrations in dorsal raphe and substantia nigra, although
      with a lower potency. Comparisons between TMIQ and MPTP showed that they were
      approximately equipotent in depleting dopamine in the substantia nigra,
      hypothalamus, and dorsal raphe. Pretreatment of animals with a combination of
      monoamine oxidase A and B inhibitors completely prevented the TMIQ-induced
      reductions in dopamine concentrations in substantia nigra and hypothalamus.
      Direct unilateral intrastriatal injections of TMIQ produced marked ipsilateral
      reductions in striatal dopamine, correlating with a behavioural response
      consisting of turning towards the side of injection. The results suggest that
      TMIQ should be evaluated further as a possible MPTP-like compound, which may
      derive from endogenous beta-hydroxylated catecholamines.

PMID- 7504087
TI  - Chicken tyrosine hydroxylase gene: isolation and functional characterization of
      the 5' flanking region.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of
      catecholamines. We describe here the isolation of the chicken TH gene and the
      analysis of 3 kb of its 5' flanking region. The chicken TH transcription unit
      spans 19 kb. The 60-bp proximal promoter contains a TATA box and a cyclic AMP
      response element (CRE) sequence. The 5' flanking region contains several AP1-,
      AP2-, and octamer-like sequences as well as a glucocorticoid response element at
      position -1.4 kb. A construct containing the 3-kb 5' flanking DNA fused to the
      chloramphenicol acetyltransferase (CAT) gene was transiently transfected into
      PC12 cells, and the effect of various effectors was tested. Only forskolin
      increased the CAT activity, likely owing to the presence of the CRE sequence.
      Constructs prepared by progressively deleting the 5' flanking DNA were
      transfected into PC12 and QT6 (quail transformed fibroblasts) cells. In both cell
      types, the transcriptional activity increased with deletion of the 5' flanking
      region. These results show that the 60-bp region containing the TATA box and the
      CRE is sufficient to act as a constitutive promoter for the chicken TH gene and
      that this region appears to be negatively controlled by upstream sequences.

PMID- 7504088
TI  - A previous potassium stimulation enhances the increases of striatal extracellular
      dopamine and 5-hydroxytryptamine during global ischaemia under simulated
      penumbral conditions.
AB  - The effect of a previous K+ stimulation on striatal extracellular monoamine
      levels during global ischaemia, under simulated penumbral conditions, was
      investigated. Rats were implanted with microdialysis probes in both striata,
      monoamine release was stimulated unilaterally by adding K+ (100 mM, 20 min) to
      the artificial CSF perfused through one probe, and bilateral partial ischaemia
      was imposed after monoamine levels had returned to basal values or below.
      Resultant increases in dialysate levels of dopamine and 5-hydroxytryptamine were
      markedly and significantly greater on the side previously exposed to K+, even
      though electrophysiological measurements indicated similarly severe ischaemia on
      both sides. Associated monoamine metabolite changes did not differ significantly
      between the two sides. There was no evidence of greater neuronal loss in the K(+)
      stimulated striata 7 days after ischaemia. However, striatal tissue probably
      exposed to the highest concentrations of K+ could not be examined because of
      extensive gliosis around the probe.

PMID- 7504089
TI  - NMDA and AMPA receptors in transgenic mice expressing human beta-amyloid protein.
AB  - The human beta-amyloid protein may play an important, possibly primary, role in
      the pathogenesis of Alzheimer's disease (AD), and it appears to potentiate the
      susceptibility of neurons to excitotoxicity. AD is associated with alterations in
      the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) subtypes of glutamate receptors, and it has been suggested
      that excitotoxicity may play a role in neuronal damage in AD. In this study, we
      have used quantitative receptor autoradiography to examine NMDA and AMPA
      receptors in transgenic mice that contain the gene for the carboxyl-terminal 100
      amino acids of the human amyloid precursor protein, beginning with the beta
      amyloid region, which is under the control of the JC viral early region promoter.
      Reverse transcriptase-polymerase chain reaction confirmed that the brains of
      transgenic mice expressed beta-amyloid mRNA and that control mice did not. NMDA
      receptors, assessed with [3H]MK-801, were unchanged in the transgenic compared
      with the control mice. In the transgenic mice, there were no significant changes
      in [3H]AMPA receptor binding compared with controls. This study represents the
      first attempt to evaluate in transgenic mice the in vivo interaction between beta
      amyloid expression and excitatory amino acid receptors.

PMID- 7504090
TI  - Induction of experimental autoimmune encephalomyelitis in rats and immune
      response to myelin basic protein in lipid-bound form.
AB  - Encephalitogenic activity of myelin basic protein (MBP) isolated in a form
      retaining binding to all myelin lipids was tested in Lewis rats. Immunization
      with this new stable lipid-bound and native-like preparation (LB-MBP), induced
      experimental autoimmune encephalomyelitis (EAE) as intensively as the classical
      lipid free MBP (LF-MBP). During the course of the disease, high affinity specific
      response to LB-MBP and high frequency of LB-MBP specific precursors was observed
      in peripheral lymphoid organs, indicating that the disease occurred in presence
      of anti LB-MBP specific T-cell responsivity. Short term lines, generated from
      lymphocytes collected at the onset of the disease from LB-MBP immunized rats,
      showed a strong dose-dependent response to LB-MBP, but not to LF-MBP. The present
      data indicate that in rat, LB-MBP maintains encephalitogenic activity and induces
      expansion of a specific T-cell population. These data suggest also that LB-MBP is
      a new autoantigen that may be relevant in human diseases.

PMID- 7504091
TI  - P-VABEC: a prospective study of a new weekly chemotherapy regimen for elderly
      aggressive non-Hodgkin's lymphoma.
AB  - PURPOSE: To evaluate, in a prospective trial, a new combination chemotherapy
      specifically designed for elderly patients. PATIENTS AND METHODS: From October
      1988 to December 1990, 60 previously untreated patients older than 60 years of
      age with aggressive non-Hodgkin's lymphoma (NHL) were treated at our institution
      with a new weekly alternating six-drug chemotherapy regimen, P-VABEC. The
      schedule consisted of doxorubicin, etoposide, and cyclophosphamide alternated
      weekly with vincristine and bleomycin. Oral prednisone was administered daily
      during the entire treatment period. Twenty-six of 60 patients were treated for a
      total of eight courses and 34 of 60 for 12 courses. RESULTS: A total of 45
      patients (75%) achieved a complete response (CR), 10 (17%) a partial response
      (PR), and five (8%) no response. So far, 20 of 45 CR patients have relapsed, four
      of 10 PR patients have progressed, and three patients have died while in CR.
      Twenty-eight patients are still alive and responding (22 CRs, six PRs) after a
      median follow-up of 25 months. The projected overall survival (OS), disease-free
      survival (DFS), and event-free survival (EFS) rates at 2 years were 64%, 57%, and
      55%, respectively. The outcome of patients treated with eight courses was similar
      to that of those who received 12 courses of P-VABEC in terms of CR rate and
      actuarial curves of OS, DFS, and EFS. Hematologic toxicity was mild in all
      patients. CONCLUSION: The P-VABEC regimen is active, well tolerated, and one of
      the briefest first-line chemotherapy regimens so far reported in the treatment of
      elderly patients with aggressive NHL. However, prospective randomized trials are
      needed to establish the real advantage of this regimen compared with other
      standard chemotherapy regimens.

PMID- 7504092
TI  - What about dental economics for the 1990s?
AB  - A slowdown in per capita dental expenditures is projected through the year 2000.
      However, reduction in the "production" of new dentists will offset these economic
      developments and result in a continued favorable economic environment.

PMID- 7504093
TI  - A multiple language health history for dental practice.
AB  - A uniform health history form in seven languages, plus English, is presented.
      They may be copied for use by private practitioners, with the English form as a
      standard referrant for the dentist.

PMID- 7504094
TI  - Maxillary and mandibular reconstruction in preparation for endosseous implants.
AB  - Bony and soft tissue deficiencies can deter esthetic, functional and prosthetic
      rehabilitation. Modern surgical techniques using bone or composite grafts to
      reconstruct or augment implant sites are reviewed.

PMID- 7504095
TI  - An unusual odontoma.
AB  - A case involving the unusual radiographic appearance of an odontoma, its surgical
      management and the post-operative sequela is presented and discussed. The final
      diagnosis emphasizes the need for thorough microscopic examination. Cysts and
      neoplasms can arise from the odontogenic epithelial component of this anomaly and
      lead to further complications, including more extensive surgical intervention.

PMID- 7504096
TI  - Mechanism of oxyhemoglobin-induced release of endothelin-1 from cultured vascular
      endothelial cells and smooth-muscle cells.
AB  - Release of endothelin-1 from cultured endothelial cells can be induced with
      oxyhemoglobin (oxyHb). The present study was conducted to explore whether oxyHb
      affects the release of endothelin-1 and the induction of endothelin-1 messenger
      ribonucleic acid (mRNA) and to examine the mechanism whereby oxyHb induces
      endothelin-1 production in cultured vascular smooth-muscle cells as well as in
      cultured endothelial cells. Oxyhemoglobin produces concentration-dependent (0.1
      to 10 microM) and time-dependent (0 to 24 hours) increases in immunoreactive
      endothelin-1 in conditioned medium from bovine arterial endothelial cells.
      Oxyhemoglobin induces immunoreactive endothelin-1 in rat aortic smooth-muscle
      cells in the same fashion, although the rate is 30-fold less than that of
      endothelial cells. This promoting effect is much higher than that of other
      stimulators such as thrombin and phorbol 12-myristate 13-acetate. Northern blot
      analysis of total RNA from endothelial cells also showed endothelin-1 mRNA
      induction. Staurosporine, a protein kinase C (PKC) inhibitor, inhibited oxyHb
      induced endothelin-1 production in both vascular endothelial and smooth-muscle
      cells, whereas an increase of intracellular cyclic adenosine monophosphate (cAMP)
      by forskolin or an addition of 8-bromo-cAMP only inhibited this effect in smooth
      muscle cells. These findings suggest that oxyHb-induced endothelin-1 production
      in endothelial cells is regulated by PKC, and in smooth-muscle cells by both PKC
      and the cAMP-dependent pathway. The production of endothelin, the most potent
      vasoconstrictor, in both vascular endothelial and smooth-muscle cells by oxyHb
      may have significance in the pathogenesis of cerebral vasospasm.

PMID- 7504097
TI  - Pancreatic adenocarcinoma: a review for primary care physicians.
AB  - Adenocarcinoma of the pancreas is becoming an increasingly common disease. The
      differential diagnosis of pancreatic adenocarcinoma is that of obstructive
      jaundice. Suspicious findings on history and physical examination can be
      confirmed with appropriate laboratory and radiologic testing. Approximately 20%
      of patients with small lesions and no metastatic disease may be cured with
      resection. The operative mortality and morbidity for major pancreatic resections
      is now sufficiently low to warrant a more aggressive approach to these patients.

PMID- 7504098
TI  - Precipitated withdrawal by pentazocine in methadone-maintained volunteers.
AB  - Pentazocine is a partial mu agonist opioid with one-half to one-sixth the
      parenteral analgesic potency of morphine. The purpose of this study was to
      characterize the effects of pentazocine in comparison to naloxone (an opioid
      antagonist), hydromorphone (an opioid mu agonist) and saline in methadone
      dependent volunteers by using the same experimental methods used previously in
      the study of the opioid analgesics buprenorphine, butorphanol and nalbuphine. In
      a residential laboratory, five volunteer male opioid abusers, maintained on 30 mg
      p.o. of methadone daily, underwent pharmacological challenges 2 to 3 times per
      week. Pharmacological challenges consisted of a double-blind i.m. injection of:
      pentazocine (dose range 7.5-120 mg), hydromorphone (5 and 10 mg), naloxone (0.1
      and 0.2 mg) or saline. Injections were given 20 hr after the last dose of
      methadone. Measures included physiological indices and self-reports and observer
      ratings of drug effects. Naloxone and hydromorphone produced characteristic
      antagonist-like and agonist-like effects, respectively, on subjective, observer
      and physiological indices. Pentazocine produced primarily antagonist-like
      effects, with higher doses (> = 60 mg) producing significant elevations of visual
      analog scale ratings of Drug Effects, Bad Effects and Sick; of observer ratings
      of piloerection, restlessness and adjective scores of opioid withdrawal; as well
      as increases in blood pressure, heart rate and pupil diameter and decreases in
      skin temperature. Similar to the previous study of butorphanol, the specific
      profile of effects produced by pentazocine differed from that produced by
      naloxone, suggesting non-mu effects may modulate the mu effects of pentazocine.

PMID- 7504099
TI  - Delta 9-tetrahydrocannabinol injection induces cytokine-mediated mortality of
      mice infected with Legionella pneumophila.
AB  - Delta 9-Tetrahydrocannabinol (THC) injection modulates immune cell function, but
      the significance of this in altering host resistance to infection is not
      understood. In addition, exposure to THC and other drugs of abuse during
      infection is associated with an acute mortality syndrome. We examined the effect
      of THC injection on the survival of mice infected with Legionella pneumophila
      (Lp). Mice given two injections of THC (8 mg/kg)-one 24 hr before and the second
      24 hr after a sublethal Lp infection-experienced acute collapse and death. The
      drug injection after infection caused death; deaths occurred within 30 min after
      the injection, and neither one nor two drug injections before infection resulted
      in death. The THC-induced mortality resembled cytokine-mediated shock in both
      kinetics and symptoms; therefore, sera from drug-treated animals were measured
      for the acute-phase cytokines tumor necrosis factor (TNF) and interleukin 6
      (IL6). The level of each cytokine was significantly elevated by THC treatment,
      suggesting a role in the observed mortality. To directly test this role, mice
      were administered a single injection of either anti-TNF alpha, anti-IL6, or a
      mixture of anti-IL1 alpha and -IL1 beta antibodies 1 hr before the second THC
      injection. Results showed that each antibody treatment protected the mice, with
      anti-IL6 being the most effective. Fluctuations in blood granulocytes levels also
      supported a role of acute-phase cytokines in THC-induced mortality. These results
      show that THC injection increases the blood levels of acute-phase cytokines in
      infected animal and that these elevated levels, at least in part, account for the
      mortality induced by THC injection.

PMID- 7504100
TI  - A selective agonist of endothelin type B receptor, IRL 1620, stimulates cyclic
      GMP increase via nitric oxide formation in rat aorta.
AB  - The signal transduction pathways of endothelin (ET)-induced vasorelaxation in rat
      aorta were investigated. An agonist for ETB receptors, IRL 1620, induced
      transient increases in cytosolic Ca++ (peak at about 10 sec) and cyclic GMP (peak
      at about 20 sec) accompanied by transient vasorelaxation (peak at about 60 sec)
      in aortic strips precontracted with 100 nM norepinephrine. The cyclic GMP content
      was increased 3- to 6-fold from the basal level (1.6 +/- 0.2 fmol/micrograms of
      protein) with 1 nM to 1 microM IRL 1620. The cyclic GMP elevation was endothelium
      dependent, abolished in the presence of 100 microM NG-monomethyl-L-arginine, an
      inhibitor of nitric oxide synthase, and recovered after the further addition of 1
      mM L-arginine. An ETB receptor antagonist, IRL 1038 (3 microM), inhibited
      completely the cyclic GMP increase induced by 100 nM IRL 1620 (8.1 +/- 0.6
      fmol/micrograms of protein) without affecting the basal level. On the other hand,
      an ETA receptor antagonist, 3 microM BQ-123, enhanced significantly both the
      basal level (3.7 +/- 0.6 fmol/micrograms of protein) and the IRL IRL 1620-induced
      production (12.2 +/- 0.8 fmol/micrograms of protein) of cyclic GMP. Specific
      binding sites for [125I]IRL 1620 were detected in rat aortic membranes with a
      dissociation constant of 37.0 pM and maximal binding capacity of 36.6 fmol/mg of
      protein, which disappeared after removing the endothelium. Unlabeled ET-1, ET-3,
      IRL 1620 and IRL 1038, but not BQ-123, displaced the binding of [125I]IRL 1620
      with inhibitory constants of 38.5 pM, 36.6 pM, 97.8 pM and 8.9 nM,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504101
TI  - Permeability enhancement in Caco-2 cell monolayers by sodium salicylate and
      sodium taurodihydrofusidate: assessment of effect-reversibility and imaging of
      transepithelial transport routes by confocal laser scanning microscopy.
AB  - The effects of sodium salicylate and sodium tauro-24,25-dihydrofusidate (STDHF)
      on the aqueous permeability of confluent monolayers of Caco-2 cells were studied.
      Measurements of transepithelial electrical resistance (TEER) showed a
      concentration-dependent effect of both compounds after apical incubation for 1
      hr. Reductions in TEER resulting from EC50 concentrations (2.8 mM for STDHF; 173
      mM for salicylate) were reversible within 5.75 hr. The transpithelial fluxes of
      two hydrophilic model compounds, sodium fluorescein F (molecular weight 376) and
      a fluorescein isothiocyanate-labeled dextran (mean molecular weight 4000) was
      significantly increased by STDHF (2.8 mM). Sodium salicylate (173 mM) only
      enhanced the transport of sodium fluorescein significantly. At the EC50
      concentrations, confocal laser scanning microscopy (CLSM) visualized both
      fluorescent tracers mainly in the paracellular route. With higher enhancer
      concentrations (373 mM sodium salicylate and 8 mM STDHF), both transport markers
      appeared intracellularly as a result of cell death. STDHF rapidly extracted an
      exogenous lipophilic membrane probe, 5-(N-hexadecanoyl)aminofluorescein (HEDAF),
      from the apical part of Caco-2 plasma membranes, indicating qualitatively that
      STDHF interacts with the lipid portion of cell membranes. These results suggest
      that both sodium salicylate and STDHF can be used to reversibly increase
      paracellular permeability of Caco-2 cell monolayers, whereby STDHF appears to be
      advantageous compared to sodium salicylate. By adapting the Costar cell culture
      system to CLSM, we have shown that this technique is suitable to study membrane
      interactions qualitatively and for visualizing transport routes of hydrophilic
      tracers through nonfixed, filter-grown monolayers.

PMID- 7504102
TI  - Microvascular substance P binding to normal and inflamed rat and human synovium.
AB  - The regulatory peptide substance P has been implicated in the development and
      persistence of inflammatory synovitis. The authors used quantitative in vitro
      receptor autoradiography to compare synovial binding of 125Iodine-Bolton Hunter
      labeled substance P ([125I]BH-SP) in rats and humans and between uniflamed and
      persistently inflamed synovium. [125I]BH-SP binding to microvascular endothelium
      paralleled the distribution of substance P-immunoreactive nerves and had
      characteristics of the neurokinin (NK) 1 class of tachykinin receptor. Specific
      binding was inhibited by the selective NK1 receptor antagonist, FK888, and the
      dual NK1/NK2 receptor antagonist FK224, with Hill coefficients near unity. FK888
      was > 1000 times and FK224 > 10 times more potent at inhibiting binding in human
      compared with rat synovium. Synovium from patients and rats with chronic
      arthritis contained heterogeneously distributed inflammatory cell infiltrates.
      For the 10 microvessels with the densest [125I]BH-SP binding in each section, no
      significant differences in binding density, affinity, or Ki values for substance
      P, FK888 or FK224 were found between synovium from naive and monoarthritic rats,
      nor between that from patients with rheumatoid arthritis or osteoarthritis.
      However, in both rat and human specimens, microscopic examination suggested that
      microvascular [125I]BH-SP binding in intensely infiltrated regions of synovium
      was less dense than in adjacent, less infiltrated areas. It was concluded that
      NK1 receptors are similarly distributed in rat and human synovium but show major
      differences in selectivity for antagonists such as FK888. NK1 receptors in
      synovium may mediate proinflammatory actions of locally released substance P;
      defective neurovascular regulation may contribute to the persistence of chronic
      arthritis.

PMID- 7504103
TI  - Serotonin inhibits Ca2+ currents in porcine melanotrophs by activating 5-HT1C and
      5-HT1A receptors.
AB  - 1. We have investigated the effect of serotonin (5-HT) on Ca2+ currents in
      cultured porcine pituitary intermediate lobe (IL) cells. Electrophysiological
      recordings were performed in the whole-cell configuration of the patch-clamp
      technique. All membrane currents other than Ca2+ currents were blocked
      pharmacologically and by ionic substitution. 2. Two types of Ca2+ currents were
      recorded in IL cells, differing by their activation and inactivation properties.
      The first type of Ca2+ current was activated at membrane potentials more positive
      than -60 mV and had a transient time course during the 100 ms depolarizing
      voltage steps. The properties of this current correspond to those of the T-type
      or low-voltage-activated Ca2+ current. The second type of Ca2+ current had a
      threshold for activation between -30 and -20 mV and showed no sign of
      inactivation with time during the voltage steps. The properties of this current
      are similar to those of the L-type or high-voltage-activated Ca2+ current. 3.
      Current to voltage (I-V) relationships obtained either by conventional 100 ms
      voltage steps from a holding potential (VH) of -100 mV to various test potentials
      or by 800 ms voltage ramps from -100 to +50mV matched one another closely and
      showed two inward current humps corresponding to the activation of the T-type and
      L-type Ca2+ currents respectively. The ramp protocol was used to characterize the
      effect of 5-HT on the Ca2+ current I-V relationship. 4. 5-HT (100nM to 50 microM)
      reversibly inhibited the amplitude of the Ca2+ current triggered by 100 ms
      voltage jumps from a Vh of -100 mV to a test potential of 0 mV. 5. The effect of
      5-HT was dose dependent with a threshold between 10 and 100 nM and a maximal
      effect at 10 microM. At a concentration of 10 microM, the average inhibition of
      Ca2+ current by 5-HT was 18.3 +/- 6.5% (n = 27). 5-HT inhibited Ba2+ current in a
      similar fashion. 6. When examining the effect of 5-HT on Ca2+ current I-V
      relationships, we observed a reversible inhibition of the high-threshold
      component corresponding to the L-type Ca2+ current. We never observed any effect
      of 5-HT on the T-type current. 7. The effect of 5-HT (10 microM) was antagonized
      to various extents by mianserin (1 microM) but not by ketanserin (0.1 microM),
      suggesting the involvement of 5-HT1C receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504104
TI  - Evidence for more than one type of non-NMDA receptor in outside-out patches from
      cerebellar granule cells of the rat.
AB  - 1. Application of non-NMDA (non-N-methyl-D-aspartate) receptor agonists onto
      outside-out patches of cerebellar granule cells gave two characteristic types of
      response (in different patches) which we have referred to as 'high conductance'
      and 'low conductance' responses. At a qualitative level these patches could be
      readily distinguished by the size of the noise increase accompanying their
      membrane currents. 2. In high conductance patches both AMPA (alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid) and kainate gave discrete single
      channel conductances (10-30 pS), while in low conductance patches, AMPA produced
      small discrete events (6-10 pS), and kainate opened channels with conductances
      too small to be directly resolved. All patches examined contained NMDA receptor
      channels with characteristic 50 and 40 pS conductance levels. 3. Despite the
      marked differences in single-channel conductances, kainate dose-response curves
      constructed for high and low conductance patches had similar EC50 values of
      approximately 150 microM. 4. Spectral analysis of low conductance kainate
      responses gave an estimated channel conductance of approximately 1.5 pS. In these
      same low conductance patches AMPA produced discrete openings with two conductance
      levels; their mean conductances (and relative proportions) were 6 (87%) and 10 pS
      (13%). 5. In high conductance patches, glutamate (10-30 microM), AMPA (3-10
      microM), and kainate (10-30 microM), each activated non-NMDA channels with three
      multiple conductance levels. The amplitudes of these conductance levels
      (approximately 10, 20 and 30 pS) were similar for each of the agonists, and their
      relative proportions (i.e. areas in the amplitude histograms) were constant for
      all three agonists. In addition, the relative proportion of levels was constant
      between patches, and all three levels were invariably present. These observations
      are all consistent with the idea that the three multiple conductances originate
      from a single receptor channel, activated by AMPA, kainate and glutamate. 6. Non
      NMDA single-channel current-voltage (I-V) plots showed outward rectification in
      high conductance patches. For all three multiple conductance levels the ratio of
      outward to inward single-channel slope conductance was 1.8 +/- 0.1 and this
      rectification remained present in symmetrical Na+ solutions. 7. In high
      conductance patches, the events produced by a rapid application of 20-50 microM
      glutamate were compared with those activated during steady-state
      application.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504106
TI  - Effects of pancreatic polypeptide on insulin action in exocrine secretion of
      isolated rat pancreas.
AB  - 1. Effects of pancreatic polypeptide (PP) on insulin action in pancreatic
      exocrine secretion was investigated by using an isolated rat pancreas that was
      perfused with Krebs-Henseleit solution containing 2.5 mM glucose, 0.1% bovine
      serum albumin and 3% Dextran T-70 at a vascular flow rate of 1.2 ml min-1. 2.
      Cholecystokinin-8 (CCK-8) at a concentration of 14 pM stimulated basal flow rate
      and amylase output of the isolated pancreas. Twenty-five millimolar glucose not
      only increased the basal flow rate and amylase output but also potentiated the
      CCK-stimulated flow rate and amylase output. 3. Porcine insulin, administered
      intra-arterially at a concentration of 100 nM, also increased the basal flow rate
      and amylase output, and also potentiated the CCK-stimulated flow rate and amylase
      output. 4. Rat PP, given intra-arterially at a concentration of 10 pM, completely
      abolished the potentiation effects of both the 25 mM glucose and the exogenous
      insulin on the CCK-stimulated flow rate and amylase output. Rat PP also inhibited
      the flow rate and amylase output increased by either 25 mM glucose alone or
      exogenous insulin alone. However, rat PP did not change the flow rate and amylase
      output stimulated by CCK-8 alone. 5. These results indicate that insulin is an
      important stimulatory hormone of pancreatic exocrine secretion, and that PP
      exerts the inhibitory role in pancreatic exocrine secretion by modulating the
      insulin action.

PMID- 7504105
TI  - Cellular mechanism of acetylcholine-induced response in dissociated outer hair
      cells of guinea-pig cochlea.
AB  - 1. The acetylcholine (ACh)-induced currents (IACh) in dissociated outer hair
      cells (OHCs) of guinea-pig cochlea were investigated using the whole-cell patch
      clamp technique, in both conventional and nystatin perforated-patch
      configurations. 2. ACh and carbamylcholine (CCh) induced outward currents at a
      holding potential (VH) of -60 mV in the perforated-patch configuration. The IACh
      increased in a sigmoidal fashion over the concentration range between 3 x 10(-6)
      and 10(-3) M. The dissociation constant (KD) was 1.7 x 10(-5) M and the Hill
      coefficient (n) was 2.7. The KD and n for CCh were 8.7 x 10(-5) M and 2.2,
      respectively. Neither nicotine nor muscarine induced any detectable current up to
      a concentration of 10(-3) M. 3. Various muscarinic agonists such as oxotremorine
      M, McN-A-343 and oxotremorine could also induce the outward currents, although
      these current amplitudes were about one-third that of ACh, indicating that they
      were partial agonists. 4. The muscarinic antagonists atropine, 4-DAMP, AF-DX 116
      and pirenzepine inhibited the IACh in a concentration-dependent manner. The half
      inhibitory concentrations (IC50) for atropine, 4-DAMP, AF-DX 116 and pirenzepine
      were 4.8 x 10(-6), 6.2 x 10(-6), 2.1 x 10(-5) and 2.9 x 10(-4) M, respectively.
      5. When the extracellular Ca2+ concentration ([Ca2+])o) was reduced to lower than
      1 mM, the amplitude of IACh, abruptly decreased. In a nominally Ca(2+)-free
      external solution ACh did not induce any current. The increase of [Ca2+]o beyond
      1 mM did not change the IACh. 6. When OHCs were perfused intracellularly with a
      pipette solution containing 10 mM BAPTA in the conventional whole-cell mode, ACh
      could not induce outward K+ currents. The Ca2+ ionophore A23187 induced an
      outward current. These results indicate that intracellular Ca2+ is involved in
      the ACh response. 7. Calmodulin inhibitors such as chlorpromazine, W-7 and
      trifluoperazine inhibited the IACh in a concentration-dependent manner. 8. When
      OHCs were dialysed with either 100 microM GDP beta S or 1 micrograms/ml pertussis
      toxin (PTX) through the patch pipette at a VH of -60 mV, the IACh diminished
      within 10 min, whereas the IACh of the control remained steady for over 20 min,
      suggesting that a PTX-sensitive G-protein is involved in the ACh
      response.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504107
TI  - Modulation of acetylcholine-elicited currents in clonal rat phaeochromocytoma
      (PC12) cells by internal polyphosphates.
AB  - 1. Whole-cell voltage clamp techniques were used to examine acetylcholine (ACh)
      elicited currents in differentiated cells of the rat phaeochromocytoma cell line,
      PC12. 2. In the absence of intracellular Mg2+, the whole-cell current-voltage
      relationship for the ACh-elicited current displayed inward rectification which
      was reduced in part by the presence of 5 mM internal adenosine 5'-triphosphate
      (ATP). 3. The reduction in the rectification attributed to ATP developed over the
      first 15-20 min of whole-cell recording. Similar results were obtained with a non
      hydrolysable ATP analogue, adenosine-5'-O-3-thiotriphosphate (ATP gamma S), or
      cytosine 5'-triphosphate (CTP) in the internal solution, but not with adenosine
      5'-diphosphate (ADP) or pyrophosphate. 4. The magnitude of the ACh-elicited
      current was also dependent on recording time and the composition of the internal
      pipette solution. The magnitude of the peak ACh-elicited current increased over
      time when the cell was internally perfused with the control solution or a pipette
      solution containing pyrophosphate, ATP gamma S, or ADP. The largest sustained
      increases in ACh-elicited current were observed in the presence of internal
      pyrophosphate or ATP gamma S. In contrast, with internal ATP or CTP, the whole
      cell current initially increased, then steadily decreased with recording time. 5.
      The desensitization rate of the ACh-elicited current increased with recording
      time irrespective of the composition of the intracellular solution. 6. The
      actions of the compounds tested make it likely that the changes in the whole-cell
      current-voltage relationship, peak current, and desensitization are produced by
      separate mechanisms. The mechanisms underlying these changes are unknown, but the
      ability of the compounds to chelate divalent cations is unlikely to be the
      explanation. Other unlikely explanations include phosphorylation of the ACh
      receptor or regulation by GTP-binding proteins.

PMID- 7504108
TI  - Whole-cell currents in isolated resting Necturus gastric oxynticopeptic cells.
AB  - 1. Necturus gastric mucosa secretes Cl- actively across the gastric glands which
      are composed almost entirely of acid- and enzyme-secreting oxynticopeptic cells.
      Single channel studies on Necturus oxynticopeptic cells have shown that the
      basolateral membrane possesses multiple K(+)-selective channels but no observable
      Cl- channels while the apical membrane has Cl- channels but no observable K+
      channels. To relate these channel properties to the conductance of the whole cell
      we have investigated the macroscopic membrane currents with conventional whole
      cell patch-clamp techniques. 2. When bathed in amphibian Ringer solution, gastric
      oxynticopeptic cells had a membrane resistance of 47.8 +/- 2.8 M omega and a
      membrane capacitance of 75.5 +/- 2.7 pF (n = 82). This gave a specific membrane
      resistance of 3260 +/- 160 omega cm2 (n = 82). Reversal potentials of the
      oxynticopeptic cells were -13.8 +/- 1.2 mV (n = 45) for an intracellular Cl-
      concentration ([Cl-]i) of 42 mM and were significantly more negative -24.4 +/-
      3.1 mV (n = 31, P < 0.001) for [Cl-]i = 22 mM. 3. In the absence of ATP in the
      pipette solution, there was an 80% reduction of the whole-cell current with a
      typical half-time (t1/2) of 5 min. The run-down was not observed when the pipette
      solution contained 4 mM ATP. 4. A slow and voltage-independent inhibition of 80%
      of the whole-cell currents occurred after addition of NPPB (35 microM). Ba2+ (10
      mM) produced a reversible inhibition of 20% of the total current. Together, 35
      microM NPPB and 10 mM Ba2+ eliminated 95% of the whole-cell currents. These data
      suggest that in the resting oxynticopeptic cells Cl- carried the major fraction
      of the current while K+ ions carried only a small fraction. 5. Total replacement
      of Cl- in the pipette and bath solution by gluconate- increased the membrane
      resistance to 751 +/- 104 M omega (n = 53) and shifted the reversal potential to 
      38.1 +/- 2.8 mV (n = 53). 6. Increasing the bath K+ concentration from 6 to 91 mM
      activated a current which had a high selectivity for K+ over choline+, Li+, Na+,
      Rb+ and Cs+ and was independent of Cl-. The activation of this K+ current (IK*)
      by high external K+ was not seen with ATP-free pipette solution. 7. Ba2+ or Cs+
      had a voltage-dependent blocking effect of this inward K+ current. Ouabain (1 mM)
      or SCH 28080 (200 microM), specific inhibitors of the Na+,K(+)-ATPase and H+,K(+)
      ATPase, had no effect.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504109
TI  - Hyperpolarizing muscarinic responses of freshly dissociated rat hippocampal CA1
      neurones.
AB  - 1. Intracellular mechanisms of the muscarinic acetylcholine (ACh) response were
      investigated in pyramidal neurones freshly dissociated from the rat hippocampal
      CA1 region. Current recordings were made in the whole-cell mode using the
      nystatin 'perforated'-patch technique, by which the muscarinic ACh response can
      be continuously recorded without so-called 'run-down' phenomenon. The amount of
      intracellular free Ca2+ ([Ca2+]i) was fluorometrically measured using fura-2. 2.
      In current clamp conditions, ACh induced a transient hyperpolarization
      accompanied by a decrease in membrane input resistance. 3. Under voltage clamp
      conditions at a holding potential (Vh) of -40 mV, ACh induced two types of
      muscarinic currents observed either alone or together: a transient outward
      current and a slowly activating sustained inward current. 4. The ACh-induced
      transient outward current reversed the direction at K+ equilibrium potential
      (EK), and the reversal potential (EACh) shifted 56.7 mV for a tenfold change of
      extracellular K+ concentration ([K+]o). 5. The ACh-induced transient outward
      current increased in a sigmoidal fashion with increase in ACh concentration,
      where the half-maximal concentration (EC50) and the Hill coefficient (n) were 8 x
      10(-7) M and 1.9, respectively. Both muscarine and carbamylcholine mimicked the
      ACh response, but neither McN-A-343 (M1 agonist) nor oxotremorine (cardiac M2
      agonist) induced any current. 6. Muscarinic antagonists reversibly blocked the
      ACh response in a concentration-dependent manner. The inhibitory potency was in
      the order of atropine > pirenzepine > AF-DX-116. 7. The ACh-induced transient
      outward current was never recorded when [Ca2+]i was chelated by the acetoxymethyl
      ester form of 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA
      AM). On the other hand, in Ca(2+)-free external solution containing 2 mM EGTA and
      10 mM Mg2+, the ACh response was elicited by the first application and successive
      ACh applications did not induce any response. Fura-2 imaging showed that [Ca2+]i
      was increased when ACh was added to the external medium with or without Ca2+,
      though in Ca(2+)-free medium only the first application of ACh increased the
      [Ca2+]i. 8. The ACh response was not affected by pretreatment with pertussis
      toxin (PTX) but the inhibitory effect of ACh on the high-threshold Ca2+ channel
      was abolished completely. 9. Pretreatment with Li+ enhanced the amplitude of the
      transient outward current and the increase in [Ca2+]i induced by ACh. 10. The
      calmodulin antagonists W-7, chlorpromazine and trifluoperazine reversibly
      inhibited the ACh response in a concentration-dependent manner.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7504111
TI  - Hepatitis C virus--epidemiology and serological diagnosis.

PMID- 7504110
TI  - Activation of nicotinic acetylcholine receptors on cultured Drosophila and other
      insect neurones.
AB  - 1. Using whole-cell and single channel recordings, we have examined the
      properties of acetylcholine (ACh)-activated currents in neurones from larval and
      pupal Drosophila melanogaster (fruit fly), larval and embryonic Musca domestica
      (house fly), and nymphal Schistocerca gregaria (locust). 2. In all preparations,
      single channel recordings revealed two major classes of ACh-activated channels,
      with average conductances of approximately 32 and 59 pS. 3. At ACh concentrations
      from 1 to 10 microM, channel activity in Drosophila larval neurones occurs in
      bursts with an average of 1-2 openings. Open times and burst durations are
      described by one or two exponentials. Burst durations for the 32 pS channel
      (approximately 3 ms, slow component) were longer than those for the 59 pS channel
      (approximately 1.0 ms). The mean open interval duration for the 32 pS channel
      (slow component) was also longer than that of the 59 pS channel. 4. At high ACh
      (20-200 microM) concentrations, bursts of the smaller conductance channel occur
      in clusters separated by long-lived periods without channel activity.
      Considerable kinetic heterogeneity was observed among clusters. 5. The whole-cell
      dose-response curve suggests that activation of current by ACh increases up to at
      least 100 microM and that multiple ligand binding steps are involved. 6.
      Drosophila and Musca larval neuronal ACh-activated channels show some unique
      features in their cholinergic pharmacological properties: (a) they are only
      weakly activated by the potent neuromuscular nicotinic agonist suberyldicholine,
      (b) hexamethonium and decamethonium are weak, but approximately equi-effective
      blockers, and (c) alpha- and kappa-bungarotoxin (BTX) both blocked reversibly,
      though alpha-BTX appears to be the more potent inhibitor.

PMID- 7504112
TI  - Antibody response to the 89-kDa outer membrane protein of Brucella in bovine
      brucellosis.
AB  - The antibody response of cattle to the minor 89-kDa outer-membrane protein (OMP)
      of brucella was measured by indirect ELISA with the purified protein and compared
      with the antibody response to smooth lipopolysaccharide (S-LPS). Pre-incubating
      sera with sonicated cell extracts of Escherichia coli prevented the binding of
      antibodies from uninfected animals to the 89-kDa OMP, suggesting the presence of
      one or more cross-reactive epitopes on this protein. In cattle infected
      experimentally with Brucella abortus, the antibody response to the 89-kDa OMP was
      later and less intense than that to S-LPS. In naturally infected cattle, 68% of
      animals showing an antibody response to S-LPS also showed an antibody response to
      the 89-kDa OMP. Results indicate that specific epitopes of the 89-kDa OMP in
      combination with those of other OMPs could be useful for diagnosis of brucellosis
      in cattle.

PMID- 7504113
TI  - Recombinant human granulocyte colony-stimulating factor accelerates regeneration
      after T-2 toxin-induced hemopoietic injury and lessens lethality in mice.
AB  - The effects of rhG-CSF on T-2-induced leukopenia and lethal toxicity in mice were
      investigated. First, T-2 was administered by gavage to adult male mice at a dose
      of 3 mg/kg b.w. daily for 7 days, and rhG-CSF was given i.p. in daily dose of 10
      or 30 micrograms/kg b.w./day, beginning on the 2nd day, for 5 days. The
      peripheral WBC of mice receiving T-2 alone was decreased to one fourth of control
      counts, and bone marrow (BM) cell counts were also markedly diminished. The
      administration of rhG-CSF prevented those T-2-induced depressions.
      Histologically, the delation of the hematopoietic cells from BM and spleen of
      mice given T-2 was remarkably counteracted by administration of rhG-CSF. In the
      other experiment, rhG-CSF was injected i.p. for 5 days beginning on the next day
      of the 7-day T-2 administration. The recovery of WBC and BM cell counts was
      hastened by rhG-CSF reaching the control level in 6 days, and differential
      leukocyte analysis revealed an increase of neutrophils. Furthermore, simultaneous
      administration of rhG-CSF depressed the T-2-induced lethal toxicity, dose
      dependently. The results revealed that rhG-CSF possesses a potent ability to
      protect T-2-induced leukopenia and lethality in mice, and it could be as an
      antidote against T-2 and related trichothecene-induced acute intoxication.

PMID- 7504114
TI  - Transvaginal color flow Doppler sonography in the assessment of gestational
      trophoblastic disease.
AB  - The aim of this study was to evaluate the blood flow characteristics of the
      uterine artery and intratumoral vessels in patients with GTD. Twelve patients
      with GTD were evaluated with TVS, and 11 also had CFD sonography performed.
      Spectral analysis of both uterine artery and samples intratumoral and
      intramyometrial vessels revealed systolic frequencies and PI that were
      significantly higher in the uterine artery than in sampled intratumoral vessels
      (P < 0.05). Uterine artery PI correlated significantly with age (P = 0.043),
      uterine size (P = 0.003), and beta-HCG titer (P = 0.03). Intratumoral PI
      correlated significantly with uterine size (P = 0.05). Intratumoral PI did not
      correlate with patient age, the shape or orientation of the uterus, presence or
      absence of subendometrial halo, endometrial thickness or echogenicity, or
      impression of myometrial invasion. Regression analysis of beta-HCG titers on
      uterine artery and intratumoral PI revealed a linear association. TVS and color
      flow Doppler sonography are useful in the assessment of patients with GTD. The PI
      is strongly associated with prognosis and correlates with beta-HCG titers.

PMID- 7504115
TI  - Disappearance of the trophoblastic blood flow in tubal pregnancy after
      methotrexate injection.

PMID- 7504116
TI  - [Whipple's disease].

PMID- 7504117
TI  - [My work place].

PMID- 7504118
TI  - Angiogenesis in three-dimensional cultures.

PMID- 7504119
TI  - Disturbance of keratin homeostasis in griseofulvin-intoxicated mouse liver.
AB  - BACKGROUND: Alterations of the hepatocytic intermediate filament (IF)
      cytoskeleton, i.e., derangement and diminution of the keratin network and
      appearance of cytoplasmic aggregates of keratin-containing material, termed
      Mallory bodies, are characteristic features of human alcoholic hepatitis. Mallory
      bodies can be experimentally produced in mouse liver by chronic griseofulvin (GF)
      administration. GF intoxication of mice is, therefore, a suitable model to study
      the mechanisms of Mallory body formation and related cytoskeletal changes.
      EXPERIMENTAL DESIGN: To investigate the correlation between morphologic
      alterations of the keratin cytoskeletal network and the mRNA levels for liver
      keratins A (8) and D (18) in this pathologic situation immunohistochemical
      studies and northern blot analyses were performed. The amount of mRNA for both
      keratins was also analyzed by nuclease S1 protection assay. RESULTS: In GF
      treated livers (4 months of treatment) an increase of mRNA for both liver
      keratins was found. This increase of mRNA was unexpected under these conditions,
      since in longterm GF-fed animals, the amount of keratin IFs was reduced as
      revealed by immunofluorescence and electron microscopy and by biochemical
      analysis of keratin proteins. In livers treated for 2 months with GF the IF
      meshwork seemed to be still intact, but the increase of RNA was already
      detectable indicating that alterations of keratin mRNA precede detectable
      morphologic alterations. When using this mRNA for in vitro translation
      experiments, strong keratin polypeptide spots could be detected by
      autoradiography of 2-dimensional gels. CONCLUSIONS: These results strongly
      suggest that in vivo under the conditions of GF intoxication posttranslational
      modifications, like phosphorylation, proteolysis and covalent cross-linking,
      could influence IF homeostasis and interfere with IF assembly. Increase of mRNA
      for liver keratins despite IF protein reduction might be due to negative feedback
      regulation.

PMID- 7504120
TI  - Insulin-like growth factor II messenger ribonucleic acid expression in Wilms
      tumor, nephrogenic rest, and kidney.
AB  - BACKGROUND: Wilms tumors (WTs) are embryonic neoplasms of the kidney that are
      believed to arise from primitive metanephrogenic blastema. Our previous reports
      and those of others indicate that WTs show an increased expression of insulin
      like growth factor II (IGF-II) mRNA. However, the precise role of IGF-II on Wilms
      tumorigenesis is not known. A central question is to determine whether the
      increased IGF-II expression in WTs simply reflects the fetal nature of WTs
      (effect), or is induced by specific changes in gene expression (cause).
      EXPERIMENTAL DESIGN: This study included 31 sporadic WTs, 7 fetal and 3 adult
      kidneys and 1 yolk sac tumor. Clinical and histologic summaries of WT cases are
      shown in Table 1. In WTs, the relative area of blastemal, epithelial, poorly
      differentiated spindle cell and heterologous cell components were assessed. Dot
      and Northern blot hybridization, using cDNA probes, were done to assess the level
      of IGF-II mRNA expression. In situ RNA hybridization was employed to localize IGF
      II transcripts. Immunohistochemistry was applied to frozen sections to
      demonstrate cytokeratin and type-IV collagen. These results were then correlated
      with the histology of WTs and their precursor lesions, i.e., nephrogenic rests
      (NRs). RESULTS: Dot blot hybridization indicated that IGF-II transcripts were 32-
      to 64-fold more abundant in WTs than in the adjacent uninvolved kidneys. In situ
      hybridization showed that WTs, NRs, and fetal kidney shared a common feature in
      which IGF-II transcripts were predominantly associated with blastema. However,
      WTs and NRs differed from fetal kidney in that occasional epithelial structures
      and dense blastema showed aberrant, sustained IGF-II expression. CONCLUSIONS: The
      data indicate two points. 1) There is an inverse correlation between
      nephroblastic differentiation and IGF-II expression in developing fetal kidney.
      2) The IGF-II expression in WTs and NRs does not simply reflect the embryonal
      nature of the tumor but is rather significantly altered, suggesting a role as a
      transforming growth factor in Wilms tumorigenesis.

PMID- 7504121
TI  - Acute-phase proteins in response to tumor growth.
AB  - This study has evaluated the relationship between tumor growth and induction of
      acute-phase proteins. It has also determined whether an intact cellular immunity
      is obligatory for a fully expressed acute-phase plasma protein response in the
      presence of a highly antigenic tumor. Quantitatively, acute-phase responses
      (protein synthesis, plasma concentrations, hepatic RNA content, anorexia) were
      proportional to tumor burden. Anti-inflammatory drugs (indomethacin 1
      micrograms/g body wt, dexamethasone 0.5 micrograms/g body wt) had no direct
      effect on the attenuation of the systemic acute-phase responses, but did affect
      them indirectly by decreasing tumor growth. Immune suppression (cyclosporine A at
      20 or 60 micrograms/g body wt) had no effect on either acute-phase reactions or
      local tumor growth. In endotoxin-stimulated (lipopolysaccharide) normal mice,
      immune suppression aggravated anorexia and caused high mortality, while
      dexamethasone partly reversed these effects in endotoxin-stimulated mice. Plasma
      levels of acute-phase proteins correlated to circulating levels of IL-6 in
      untreated tumor-bearing mice, but this relationship was not obvious in either
      drug-treated tumor-bearing or endotoxin-stimulated mice. Tumor tissue induced the
      synthesis of different acute-phase proteins compared to endotoxin. However,
      disintegrated normal liver tissue induced the synthesis of serum amyloid protein
      to the same extent as the growing tumor. This effect was primarily associated
      with the mitochondrial/lysosomal and microsomal liver cell fractions. In
      conclusion, the overall acute-phase protein response is not a modulating factor
      of tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504122
TI  - Combined administration of an IK(ATP) activator and Ito blocker increases
      coronary flow independently of effects on heart rate, QT interval, and ischaemia
      induced ventricular fibrillation in rats.
AB  - The effects of combined administration of the ATP-dependent K+ channel opener
      cromakalim and the transient outward K+ current (Ito) blocker tedisamil on
      ventricular tachyarrhythmias, QT interval, and coronary flow were investigated in
      isolated rat heart (n = 12/group) subjected to 30-min regional ischaemia. When
      administered alone, beginning 5 min before onset of ischaemia and continuously
      thereafter, neither cromakalim (10 microM) nor tedisamil (3 microM) had any
      significant influence on the incidence of VF, although tedisamil abolished
      sustained VF (SVF, defined as VF lasting > 2 min). Cromakalim did not affect
      tedisamil's ability to abolish SVF when administered concurrently with tedisamil
      and had no effect on SVF when administered alone; incidences of SVF were 64, 0 (p
      < 0.05), 66, and 0% (p < 0.05) in control, tedisamil, cromakalim, and combined
      treatment groups, respectively. Occurrence of SVF was related to the width of the
      ventricular complex at 50% of repolarisation (QT50). Pretreatment with tedisamil
      widened QT50 (p < 0.05), and this effect was not attenuated by combined treatment
      with cromakalim. Cromakalim increased coronary flow (14 +/- 0.4 in controls
      versus 21 +/- 0.6 ml/min/g in cromakalim-treated hearts, p < 0.05). This effect
      was not reduced by coadministration of tedisamil (20 +/- 0.9 ml/min/g in hearts
      cotreated with both drugs). Tedisamil alone had no significant effect on coronary
      flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504123
TI  - Increased 86Rb+ efflux from perfused rat hearts exposed to alpha 1-adrenergic
      stimulation.
AB  - Stimulation of myocardial alpha 1-adrenoceptors mediates changes in potassium
      fluxes across the sarcolemma. We studied the effect of alpha 1-adrenoceptor
      stimulation (5 x 10(-5) M phenylephrine with addition of 10(-6) M timolol) on
      potassium efflux by use of 86Rb+ efflux from isolated rat hearts perfused in a
      nonrecirculation system. The hearts were loaded with 86Rb+, followed by washout
      during which they were exposed to alpha 1-adrenergic stimulation with or without
      addition of the Na+/K(+)-ATPase inhibitor ouabain (10(-5) M). 86Rb+ content in
      perfusate fractions during the washout period and in the hearts at the end of
      experiments was measured; 86Rb+ efflux rates were determined as the ratio between
      the radioactivity of the perfusate fractions and the corresponding radioactivity
      contents of the hearts. alpha 1-adrenoceptor stimulation evoked a gradual
      increase in 86Rb+ efflux amounting to 30% of reference value after 20 min. With
      addition of ouabain, the alpha 1-adrenergic increase in 86Rb+ efflux developed
      faster and reached a maximum of approximately 40% of basal after approximately 10
      min. The effects both with and without addition of ouabain were prevented by the
      alpha 1-adrenoceptor blocker prazosin (10(-6) M). Results indicate that increased
      potassium efflux is a part of alpha 1-adrenergic heart effects.

PMID- 7504124
TI  - An effect model for the assessment of drug benefit: example of antiarrhythmic
      drugs in postmyocardial infarction patients.
AB  - An effect model is a function that defines the relationship between the clinical
      efficacy of a treatment and specific covariates. The simplest effect model
      defines the probability of failure in treated patients as a linear function of
      the probability for these patients if they received no treatment. We used this
      approach to explore the effects of Class I antiarrhythmic agents in patients
      after myocardial infarction. Evidence from one large trial, the Cardiac
      Arrhythmic Suppression Trial (CAST), and the pooling of data from several smaller
      trials suggests that these agents have harmful effects in postmyocardial
      infarction patients. The relevance of results from pooled data is dependent on
      the homogeneity of the trials and is assessed by a heterogeneity test that is
      dependent on the analytical method used, i.e., odds ratio or rate difference
      methods, which correspond to two different effect models. We have developed an
      effect model that considers both iatrogenic effects of these drugs, i.e.,
      depression of ventricular function and arrhythmogenic effects. When applied to
      the data from 13 published trials (including CAST), we found that these drugs may
      be beneficial in high-risk patients (with a 1-year mortality rate of > or = 15%)
      and that the background lethal iatrogenic effect is likely to affect low- and
      very low-risk patients (1-year mortality rate of < or = 5%). The accuracy of the
      proposed model was confirmed with use of the results from the recent CAST II
      study.

PMID- 7504125
TI  - Clinical pharmacology of intravenously administered recombinant desulfatohirudin
      (CGP 39393) in healthy volunteers.
AB  - Clinical pharmacology of the intravenously administered recombinant
      desulfatohirudin CGP 39393 was investigated in 47 healthy volunteers in a
      multicenter study. Mean peak concentrations after bolus injections of 0.1, 0.3,
      0.5, and 1.0 mg/kg were 154, 443, 764, and 1,691 nmol/L, respectively.
      Intravenous infusions of 0.1 mg/kg/h for 6 h and of 0.2 and 0.3 mg/kg/h for 6 h
      and 72 h resulted in mean steady-state levels of 78, 227, and 312 nmol/L.
      Elimination was multiexponential and dose independent. Concordant pharmacokinetic
      parameters were obtained from both i.v. bolus and infusion experiments (overall
      average total plasma clearance, 2.20 ml/min/kg; mean residence time, 2.12 h;
      volume at steady state, 0.27 L/kg). Thrombin inhibition by CGP 39393 was
      demonstrated ex vivo by the thrombin chromogenic assay (TCA), by activated
      partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time
      (PT). Following a parabolic function APTT doubled and quadrupled at CGP 39393
      concentrations of 100 and 1,000 nmol/L, respectively. Whereas TTs (bovine
      thrombin 3 or 6 IU/ml) were very sensitive to low CGP 39393 levels with
      unmeasurable clotting times at CGP 39393 concentrations greater than 30 and 60
      nmol/L, PT was prolonged by a factor of only 1.3 above baseline at 300 nmol/L.
      APTT appears to be most suitable for monitoring the anticoagulant effect of CGP
      39393 over a broad concentration range. The drug was well tolerated without
      clinically relevant bleeding episodes or other adverse events.

PMID- 7504126
TI  - Effects of an angiotensin-converting enzyme inhibitor, lisinopril, on cerebral
      blood flow autoregulation in healthy volunteers.
AB  - The effects of a single oral dose (20 mg) of lisinopril on systemic, carotid
      (pulsed Doppler), and cerebral (middle cerebral artery, transcranial Doppler)
      hemodynamics have been investigated over an 8-h period in eight healthy
      volunteers in a double-blind placebo-controlled crossover study. In addition,
      cerebral vasodilatory reserve was measured (acetazolamide test). Lisinopril did
      not affect systemic hemodynamics but it increased both common carotid artery
      blood flow (+26.2%, p < 0.01) and diameter (+4.5%, p < 0.05) after 8 h.
      Lisinopril did not affect middle cerebral artery mean blood flow velocity but
      increased cerebral resistance index (+8.1%, p < 0.05) at 4 h and cerebral
      vasodilatory reserve (+24.8%, p < 0.05). These data suggest that lisinopril
      produces a paradoxical vasoconstriction of the small cerebral arterioles. This
      vasoconstriction might be a compensatory mechanism to a dilation of large
      cerebral arteries, thus resulting in an unchanged cerebral blood flow.

PMID- 7504127
TI  - Hemodynamic and antiischemic effects of nifedipine, lacidipine, and nisoldipine
      in rat isolated working heart.
AB  - We compared two newer dihydropyridine-calcium antagonists (lacidipine and
      nisoldipine) with the classic prototype of this group, nifedipine, in the rat
      working heart preparation. The hearts were paced at a frequency of 5 Hz and
      perfused with Tyrode's solution of 37 degrees C. The following five parameters
      were determined: left ventricular pressure (LVP), maximal rate of pressure
      increase (+dP/dtmax), aortic output (AO), coronary blood flow (CBF), and cardiac
      output (CO). First, dose-response curves were constructed; from these data the
      EC50 concentration for the three calcium antagonists was calculated.
      Subsequently, washout from the cardiac tissue for these three compounds was
      determined. The effects of lacidipine did not diminish during < or = 90-min
      washout, whereas the effects of nifedipine disappeared completely in 10 min. The
      effects of nisoldipine, however, disappeared partly in 10 min. In separate
      experiments, the antiischemic activity of the three calcium antagonists was
      analyzed, using low-flow ischemia. The calcium antagonists were used in a
      concentration that produced a 60% reduction in contractile force (EC60).
      Nifedipine and nisoldipine caused significant improvement in functional recovery.
      The antiischemic properties of lacidipine could not be shown because of its slow
      kinetic properties with accumulation in the membrane phase and slow kinetics with
      the channel. Nisoldipine and lacidipine appear to be more potent calcium
      antagonists as compared with nifedipine, whereas lacidipine displays a clearly
      different kinetic pattern in comparison to nifedipine and nisoldipine. In
      particular, the extremely slow onset and very long duration of action of
      lacidipine are of interest.

PMID- 7504128
TI  - Mesenteric small artery changes after vasoconstrictor infusion in young rats.
AB  - We evaluated whether chronic alpha 1-adrenergic stimulation, angiotensin II
      (AII), or increased blood pressure (BP) alters resistance arterial structure and
      function. Structural parameters and wall tension were recorded in mesenteric
      small arteries (MrA) isolated from 6-week-old normotensive Wistar Kyoto rats that
      had been infused for 4 days with saline (WKY), 2 mg/kg/day phenylephrine (WKY +
      PHE), or 0.3 mg/kg/day AII (WKY + AII) and from saline-infused spontaneously
      hypertensive rats (SHR). During the experimental period, systolic BP (SBP) did
      not change in WKY but increased in WKY + PHE, WKY + AII, and SHR. Relative
      cardiac mass did not differ between SHR and WKY, but was increased in WKY + PHE
      and WKY + AII. Stiffness and optimal lumen diameter of MrA did not differ between
      WKY and SHR and were not altered in WKY + PHE or WKY + AII. Maximal contractile
      responses and sensitivities for vasconstrictors and calcium in vessels of WKY +
      AII and SHR did not differ from those in WKY. In vessels of WKY + PHE, maximal
      responses to vasoconstrictors and sensitivities for norepinephrine (NE) and PHE
      were reduced. Relaxing responses to isoproterenol (ISO) and Na-nitroprusside did
      not differ between SHR and WKY and were not altered in WKY + PHE and WKY + AII.
      Those to acetylcholine (ACh) were reduced in WKY + PHE. Media cross-sectional
      area and media thickness were significantly larger in WKY + AII and SHR as
      compared with WKY but were not altered in WKY + PHE. These data indicate that in
      young rats AII leads to small artery hypertrophy and that neither increased BP or
      increased vasconstriction appear to be involved therein. Chronic alpha 1
      adrenergic stimulation, on the other hand, did not modify small artery structure
      but resulted in nonselective reduction of arterial smooth muscle contractile
      reactivity.

PMID- 7504129
TI  - Long-term treatment (2 years) with the HMG CoA reductase inhibitors lovastatin or
      pravastatin in combination with cholestyramine in patients with severe primary
      hypercholesterolemia.
AB  - The effects of the two HMG CoA reductase inhibitors lovastatin and pravastatin in
      combination with 12-16 g cholestyramine on serum lipids were studied in 18
      patients with severe primary hypercholesterolemia. Combined therapy of
      cholestyramine with lovastatin (80 mg daily) decreased low-density-lipoprotein
      (LDL) cholesterol by 44% (baseline 7.65 +/- 0.51 mM) and increased high-density
      lipoprotein (HDL) cholesterol by 20% (baseline 1.22 +/- 0.12 mM) in 9 patients
      after 2 years. In 9 other patients with comparable baseline lipid values,
      cholestyramine plus pravastatin (40 mg daily) reduced LDL cholesterol to a
      comparable extent after 2 years (-43%, baseline 7.71 +/- 0.44 mM) and increased
      HDL cholesterol by 18% (baseline 1.06 +/- 0.11 mM). The combination with
      lovastatin led to a significant reduction in triglycerides level by 25% (baseline
      1.63 +/- 0.24 mM), whereas the combination with pravastatin did not change
      triglycerides level (baseline 1.39 +/- 0.15 mM). Both drug regimens were well
      tolerated without serious side effects. The effects of both HMG CoA reductase
      inhibitors after 2 years were comparable to those after short-term intake and
      after 1-year therapy without loss of efficacy.

PMID- 7504130
TI  - Effects of prenylamine and AQ-A 39 on reentrant ventricular arrhythmias induced
      during the late myocardial infarction period in conscious dogs.
AB  - The effects of prenylamine (PNL) and AQ-A 39 on sustained ventricular tachycardia
      (SVT) were studied by programmed stimulation in conscious dogs 4-10 days after
      ligation of the left anterior descending (LAD) coronary artery. In 8 of 16 dogs
      developing SVT in the control, PNL (3 mg/kg intravenously, i.v.) suppressed
      inducibility of SVT and slowed the rate of tachycardia in 6 other animals. In a
      separate group of 10 dogs with inducible SVT, AQ-A 39 (4 mg/kg i.v.) abolished
      elicitation of tachycardia in 3 dogs and decreased its rate in 6 other dogs.
      Neither drug affected normal conduction significantly, but PNL impaired slow
      conduction in the infarct zone, as indicated by prolongation of late potential.
      Both agents increased the effective refractory period (ERP) of infarcted and
      normal ventricular myocardium and prolonged the corrected QT interval. PNL and AQ
      A 39 exert notable efficacy in preventing infarcted heart from severe ventricular
      arrhythmias. Prolongation of ventricular refractoriness and repolarization, as
      well as decreased slow conduction in ischemically damaged myocardium, are major
      mechanisms accounting for the effectiveness of these drugs against ventricular
      arrhythmias.

PMID- 7504131
TI  - Effects of diltiazem on force, [Ca2+]i, and energy metabolism in porcine coronary
      artery.
AB  - The effects of diltiazem, a coronary-specific calcium antagonist, on isometric
      force generation and [Ca2+]i were measured in isolated porcine coronary artery
      and related to measured changes in both oxidative and aerobic glycolytic
      metabolism. Diltiazem, at concentrations ranging from 0.1 to 100 microM,
      inhibited K+ depolarization-induced increases in tension, intracellular calcium,
      oxygen consumption, and aerobic lactate release. Inhibition of tension, free
      calcium content, and oxygen consumption was dependent on diltiazem concentration,
      whereas inhibition of aerobic lactate release was not strongly dependent on
      diltiazem concentration. Aerobic lactate release, demonstrated to be coupled to
      Na(+)-pump activity in porcine coronary artery, was inhibited by diltiazem, but
      ouabain-sensitive accumulation of potassium by potassium-depleted tissues was
      not. Diltiazem therefore appears to uncouple the relationship between Na(+)-pump
      activity and aerobic glycolysis characteristic of coronary artery metabolism.
      Depolarization-induced increases in oxygen consumption measured in untethered
      preparations to reduce active tension were also inhibited by diltiazem at
      concentrations > or = 3 microM. Diltiazem therefore inhibits depolarization
      induced increases in intracellular calcium and tension and has major effects on
      both the contractile and noncontractile components of energy metabolism in
      coronary arteries.

PMID- 7504132
TI  - Electrophysiologic effects of pirmenol, its metabolite 2, and enantiomers, on
      cardiac Purkinje fibers.
AB  - We used standard microelectrode techniques to study the electrophysiologic
      effects of pirmenol, its cis-(+) and cis-(-) enantiomers, and its metabolite 2 on
      canine Purkinje fibers. The parent compound and both enantiomers significantly
      reduced the amplitude and Vmax of phase 0 of the action potential (AP) and
      shortened AP duration (APD). No significant differences were detected in the
      concentration-dependent effects on AP characteristics among these three
      compounds. Metabolite 2 caused similar changes in the amplitude and Vmax of phase
      0, but they were of lesser magnitude. In contrast to the parent compound,
      metabolite 2 markedly prolonged repolarization. The use-dependent effects of
      pirmenol and metabolite 2 were studied. At 10(-5) M, the time constant of onset
      of use-dependent block (tau on) for pirmenol was 10.4 +/- 0.4 (mean +/- SEM)
      beats; for metabolite 2, it was 7.4 +/- 0.8 beats (p < 0.05). The time constants
      of recovery from use-dependent block (tau off) were comparable: pirmenol 18 +/- 2
      s and metabolite 2 21 +/- 6 s (p > 0.05). Pirmenol and its enantiomers have
      comparable local anesthetic effects. In contrast to pirmenol, its metabolite 2
      prolongs AP duration.

PMID- 7504133
TI  - Effect of endothelium on diabetes-induced changes in constrictor responses
      mediated by 5-hydroxytryptamine in rat aorta.
AB  - We investigated constrictor responses to 5-hydroxytryptamine (5-HT) and 1-(2,5
      dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a 5-HT2/5-HT1C receptor agonist) of
      aortic rings from 2- and 6-week streptozotocin-diabetic and vehicle control rats.
      At 10 g resting tension, maximum responses and -log EC50 values to 5-HT were
      significantly reduced in endothelium-intact and denuded aortas from 2- and 6-week
      diabetic rats relative to those from control rats (except for -log EC50 of
      endothelium-intact rings from 6-week diabetic rats). Removal of endothelium from
      aortas of 2- and 6-week diabetic and control rats caused significant increases
      both in -log EC50 values and in maximum responses to 5-HT. DOI caused marked
      contraction of endothelium-denuded aortas from control rats, but not of
      endothelium-intact aortas from control rats or aortas (either with or without
      endothelium) from diabetic rats. The nitric oxide (NO) synthase inhibitor N-nitro
      L-arginine (NOLA) significantly potentiated constrictor responses to 5-HT in
      endothelium-intact aortas from control and diabetic rats. NOLA significantly
      potentiated constrictor responses to DOI in endothelium-intact aortas from
      control rats, but not in endothelium-intact aortas from diabetic rats. These
      results suggest that for aortas from 2- and 6-week diabetic rats, the diminished
      responses to 5-HT and DOI may be a result of reductions in 5-HT2-receptor
      mediated responses of smooth muscle. The results also suggest that 5-HT and DOI
      can stimulate NO release from endothelial cells.

PMID- 7504135
TI  - Terfenadine alters action potentials in isolated canine Purkinje fibers more than
      acrivastine.
AB  - Acrivastine and terfenadine are second-generation antihistamines with similar
      pharmacologic profiles and comparable clinical efficacies for allergic rhinitis.
      However, terfenadine therapy has been associated with cardiovascular side effects
      that include prolonged QT interval, torsades de pointes, and ventricular
      fibrillation (VF). We examined the adverse effects induced by terfenadine on
      evoked action potentials (APs) in isolated canine cardiac Purkinje fibers and
      determined whether acrivastine causes similar disturbances in this preparation.
      Terfenadine produced a statistically significant decrease in the maximal rate of
      increase in the AP (dV/dt) at 10(-7) M, which corresponds to the highest plasma
      concentration observed clinically. The IC50 (mean +/- SEM) value for terfenadine
      induced inhibition of dV/dt was 1.3 +/- 0.3 x 10(-6) M. The decrease in dV/dt
      caused by terfenadine became more pronounced with faster rates of stimulation.
      Acrivastine at a concentration of 10(-5) M, a value 10 times higher than plasma
      concentrations observed in clinical studies, caused no significant changes in AP
      duration (APD) or dV/dt. The IC50 (mean +/- SEM) value for the acrivastine
      induced inhibition of dV/dt was estimated to be 8.0 +/- 3.7 x 10(-3) M.
      Terfenadine blocked the evoked AP at 3 x 10(-6) M, whereas no block was observed
      with acrivastine at 10(-3) M. The effective serum concentration of acrivastine is
      approximately 100 times higher than that of terfenadine. Because the IC50 value
      for inhibition of dV/dt for acrivastine is approximately 6,000 times greater than
      that for terfenadine, we estimate that acrivastine is approximately 60-fold less
      likely to cause disturbances in cardiac conduction than terfenadine.

PMID- 7504134
TI  - Effects of doxazosin and hydrochlorothiazide on lipid levels in Korean patients
      with essential hypertension.
AB  - Because none of the major studies used to document adverse or beneficial
      metabolic effects of antihypertensive drugs were made of non-Western patients
      with a non-Western diet, we compared doxazosin and hydrochlorothiazide in Korean
      patients receiving a Korean diet to determine if one regimen is superior to the
      other in terms of efficacy, adverse metabolic effects, or both. The randomized,
      double-blind, parallel study of Korean hypertensive patients compared the effects
      of oral doxazosin (mean +/- SD dose, 10.3 +/- 6.3 mg/day) and oral
      hydrochlorothiazide (44.0 + 11.0 mg/day) on blood pressure (BP) and lipid
      metabolism. The results of 48 patients treated for 20 weeks are reported here.
      Systolic (p < 0.001) and diastolic (p < 0.001) BP (SBP, DBP) were significantly
      lower in both groups at the end of the treatment period. Doxazosin significantly
      increased high-density-lipoprotein (HDL) cholesterol from a baseline of 1.10 +/-
      0.31 to 1.27 +/- 0.30 mM (p < 0.05) and HDL/total cholesterol from 0.25 +/- 0.1
      to 0.28 +/- 0.1 mM (p < 0.01). Hydrochlorothiazide significantly increased
      triglyceride from a baseline of 1.63 +/- 0.71 to 2.02 +/- 0.87 mM (p < 0.05). In
      contrast to Western studies, hydrochlorothiazide demonstrated no adverse effect
      on total, low-density-lipoprotein (LDL), or HDL cholesterol, or on HDL/total
      cholesterol. Indeed, HDL cholesterol was increased by 0.16 mM (p < 0.01). As in
      Western patients, doxazosin is effective for treatment of essential hypertension
      in Koreans and has no adverse effects but some beneficial effects on
      lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504136
TI  - Cofactors of constitutive nitric oxide synthase and endothelium-dependent
      relaxations in canine femoral veins.
AB  - Enzymatic production of nitric oxide (NO) in arterial endothelial cells requires
      the cofactors calmodulin and nicotinamide adenine dinucleotide phosphate (NADPH).
      Experiments were designed in investigate whether these cofactors are required for
      endothelium-dependent relaxations in canine femoral veins. Veins were removed
      from anesthetized dogs and cut into rings. Endothelium was deliberately removed
      from some rings. All rings were incubated with indomethacin (1 x 10(-5) M). In
      separate sets of experiments, rings were incubated with calmidazolium (1 x 10(-5)
      M), fendiline (1 x 10(-6) M), both inhibitors of calmodulin or diphenylene
      iodonium (1 x 10(-5) M; DPI) an inhibitor of NADPH. Concentration-response curves
      were obtained for acetylcholine (ACh), ADP, thrombin, A23187, and NO in rings
      contracted with a submaximal concentration of prostaglandin F2 alpha (PGF2 alpha)
      in the presence of the inhibitors and compared with a solvent control (dimethyl
      sulfoxide, DMSO). Relaxations to ACh, ADP, and thrombin were reduced by the
      inhibitors of both cofactors. Relaxations to A23187 were reduced by inhibitors of
      calmodulin but not NADPH; inhibitors of both NADPH and calmodulin caused no
      significant reduction in relaxations to NO. These data suggest that endothelium
      dependent relaxations in canine femoral veins are mediated by factor(s) that are
      partly dependent on calmodulin or NADPH as cofactors for their production or
      release.

PMID- 7504137
TI  - Renin-angiotensin system in thyroid dysfunction in rats.
AB  - Thyroid dysfunction produces marked cardiovascular responses; the renin
      angiotensin system (RAS) is important in control of the cardiovascular system. We
      have measured changes in the plasma RAS and in angiotensin II (AT) receptors in
      experimentally hyperthyroid, euthyroid, or hypothyroid rats. Hyperthyroidism
      activated the plasma RAS, increasing plasma angiotensinogen by 85% after 7-day
      triiodothyronine (T3) treatment, plasma renin activity (PRA) by 47% and
      concentration by 52%, and plasma AT by 1.250%. Hypothyroidism reduced plasma
      angiotensinogen by 71%, PRA by 73%, and plasma AT by 81% without altering plasma
      renin concentration (PRC). Plasma aldosterone was reduced by 39% in hyperthyroid
      rats and by 95% in hypothyroid rats. AT receptors were characterized in heart,
      liver, adrenal gland, and kidney. Cardiac, liver, and kidney AT receptor
      densities increased in hyperthyroidism by 73, 113, and 75%, respectively; adrenal
      gland receptor density decreased by 39%. Similar results were observed in
      hypothyroidism except that adrenal gland receptor density was markedly increased
      by 205%. AT receptor subtypes were characterized in ventricular homogenates by
      the selective antagonist losartan. Hyperthyroidism markedly increased AT2-subtype
      density by 204% in left ventricle, and by 304% in right ventricle and decreased
      AT1-subtype density by 38% and 31% in left and right ventricles, respectively.
      AT2-subtype density increased by 168% in hypothyroid rats; AT1-subtype density
      was unchanged. Thyroid dysfunction causes significant changes in the RAS and in
      AT receptor density, especially of the AT2 subtype. Although a physiological
      function has not yet been reported for AT2 receptors, our results suggest that
      selective AT2-receptor antagonists may prove therapeutically useful in treatment
      of cardiovascular disease in thyroid dysfunction.

PMID- 7504138
TI  - Activation of complement by Fluosol attributable to the pluronic detergent
      micelle structure.
AB  - Fluosol, a complex mixture of perfluorocarbons with a high oxygen-carrying
      capacity emulsified with the detergent pluronic F-68 and various lipids, recently
      was approved for adjuvant therapy to reduce myocardial ischemia during coronary
      angioplasty. Anaphylactoid reactions after Fluosol infusion through activation of
      the complement pathway have been reported in some patients. We examined the
      mechanism of complement activation by Fluosol. In vitro, incubation of both dog
      and human plasma with Fluosol for 1 h caused a significant reduction in total
      hemolytic complement levels (CH50). None of the individual components of Fluosol
      tested activated complement. A reduction in CH50 levels similar to that observed
      with Fluosol was obtained after incubation of dog or human plasma with the
      detergent pluronic F-68 in combination with either perfluorocarbon. In vivo, a
      bolus injection of the detergent and perfluorocarbon fully mimicked the
      anaphylactoid reaction of Fluosol previously observed in dogs, with transient
      profound hypotension, tachycardia, and reduction in CH50 levels occurring < or =
      5 min. To investigate further the mechanism by which the pluronic/perfluorocarbon
      combination activates complement, an inert dense liquid (mineral oil or silicon
      oil) substituted for the perfluorocarbons produced comparable complement
      activation both in vitro and in vivo. These observations suggest that creation of
      a larger pluronic micelle around a core of perfluorocarbons or any inert dense
      substance, causes formation of a specific surface configuration, resulting in
      activation of the complement cascade.

PMID- 7504139
TI  - Intracoronary linsidomine abolishes acetylcholine-induced vasoconstriction of
      epicardial coronary arteries.
AB  - If the vasodilation of the epicardial coronary arteries caused by linsidomine
      (SIN-1), the active metabolite of molsidomine, is well established, few data are
      available concerning the effects of SIN-1 on the acetylcholine (ACh)-induced
      vasoconstriction of epicardial coronary arteries. Fourteen patients with mild
      lesions of the left anterior descending artery (LAD) were studied. Intracoronary
      blood flow velocity was measured by a Doppler probe placed in the proximal
      segment of the LAD, and cross-sectional arterial area was assessed by
      quantitative angiography. After initial hemodynamic parameters were measured, 12
      mg papaverine was injected into the left main coronary artery. When hemodynamic
      parameters returned to baseline values, three increasing concentrations of ACh (5
      x 10(-7), 10(-6), and 5 x 10(-6) M) were selectively administered into the LAD in
      a 3 min period for each concentration. While the infusion of ACh 5 x 10(-6) M was
      continued, 1 mg SIN-1 was injected as a bolus in the ostium of the left coronary
      artery. After the injection of papaverine, blood flow increased by 197 +/- 8%,
      with a trend toward vasoconstriction of the proximal and distal segments of the
      LAD (p = NS). The ACh injection induced a dose-dependent vasoconstriction,
      reaching 51 +/- 20% on the distal segment of the LAD at the maximum concentration
      (p < 0.001). After an initial increase in coronary blood flow of 47 +/- 10 and 28
      +/- 11% during the first two concentrations of ACh, respectively, the values
      decreased after the last injection to the level of baseline values. The infusion
      of SIN-1 antagonized the ACh-induced vasoconstriction, leading to vasodilation of
      7.5 +/- 3% (p < 0.005) and 16 +/- 7% (p < 0.001) of the proximal and distal
      segments of the LAD, respectively; this was associated with an increase in
      intracoronary blood flow by 42 +/- 8%. We conclude that intracoronary
      administration of SIN-1 can antagonize the ACh-induced vasoconstriction of
      epicardial coronary arteries.

PMID- 7504140
TI  - Effects of histamine on porcine isolated myocardium: differentiation from effects
      on human tissue.
AB  - Inotropic effects of histamine have been studied extensively in many species, but
      data on porcine myocardium, often used as a model for human heart, are not
      available. We investigated inotropic effects of histamine on atrial and
      ventricular trabeculae obtained from porcine hearts. For comparison, we also
      evaluated the effects of histamine on human myocardium. Histamine caused
      concentration-dependent increases in contractile force in porcine and human
      atrial tissue [at 1 x 10(-3) M: 267 +/- 70 and 317 +/- 81 mg, or 133 +/- 17 and
      85 +/- 12% of the response to 1 x 10(-5) M norepinephrine (NE), respectively], as
      well as in porcine and human ventricular tissue (at 1 x 10(-3) M: 592 +/- 148 and
      773 +/- 203 mg, or 68 +/- 13 and 122 +/- 61% of response to 1 x 10(-5) M NE,
      respectively). Cimetidine, but not mepyramine, antagonized the contractile
      effects of histamine in porcine and human atrial tissue and in human ventricular
      tissue. In contrast, the histamine-induced positive inotropic effect in porcine
      ventricular tissue was antagonized by mepyramine but not by cimetidine.
      Propranolol failed to block the inotropic effect of histamine in all four
      tissues. These results indicate that, as with human atrial trabeculae, the
      positive inotropic effect on porcine atrial trabeculae is mediated by H2
      receptors. In contrast to human ventricular trabeculae, however, the positive
      inotropic effect on porcine ventricular trabeculae appears to be mediated by H1
      receptors.

PMID- 7504141
TI  - Bepridil improves left ventricular performance in patients with angina pectoris.
AB  - Patients with coronary artery disease and angina pectoris have abnormalities of
      left ventricular (LV) diastolic performance. These abnormalities, which exist
      when the patients are at rest and not experiencing angina, are presumably
      secondary to abnormalities of intracellular calcium metabolism. Twenty-three
      patients with chronic exertional angina pectoris participated in a placebo
      controlled, randomized, cross-over trial of bepridil hydrochloride. Angina
      frequency, nitroglycerin (NTG) consumption, and treadmill exercise capacity were
      assessed, and each patient underwent first-pass radionuclide cineangiography
      while receiving placebo or bepridil to assess LV performance. Bepridil decreased
      angina frequency from 8.5 +/- 0.6 to 4.4 +/- 1.5 episodes per week (p < 0.01) and
      NTG consumption from 7.2 +/- 2.4 to 3.6 +/- 1.5 tablets per week (p < 0.01).
      Total treadmill exercise time, time to onset of angina, and time to 1-mm ST
      segment depression increased significantly during bepridil therapy. Cardiac
      output (CO), stroke volume (SV), and ejection fraction (EF) increased at rest and
      during peak upright bicycle exercise. Peak ejection rate and peak filling rate
      increased, and time to peak ejection rate and time to peak filling rate decreased
      at rest and at peak exercise during bepridil therapy. In addition, early
      diastolic filling fraction increased and atrial filling volume decreased during
      bepridil treatment. Bepridil is effective as monotherapy for treatment of
      patients with exertional angina; its use is associated with increased exercise
      capacity and decreased angina frequency and NTG consumption as well as improved
      LV systolic and diastolic performance at rest and during peak exercise.

PMID- 7504142
TI  - In vivo regulation of human cardiac beta-adrenoceptors by a partial agonist as
      compared with a full antagonist: selective differences in coupling to adenylate
      cyclase.
AB  - Chronic therapy with the beta 1-selective adrenoceptor partial agonist xamoterol
      is not associated with the tolerance observed with other beta-adrenoceptor
      agonists. A possible explanation is that xamoterol therapy does not desensitise
      human cardiac beta-adrenoceptors in vivo. beta-Adrenoceptor density and adenylate
      cyclase activities were determined in right atrial appendages obtained from 40
      patients randomised in a double-blind fashion to receive either xamoterol or
      atenolol for at least 5 weeks before coronary artery bypass surgery. There was no
      significant difference in total or subtype beta-adrenoceptor densities, but basal
      and isoproterenol stimulated adenylate cyclase activity were significantly
      greater in the atenolol-treated group, as was the intrinsic activity of the beta
      2-adrenoceptor partial agonist procaterol, suggesting that chronic therapy with
      xamoterol does not downregulate human cardiac beta-adrenoceptors in vivo.
      Coupling of beta-adrenoceptors to adenylate cyclase, predominantly mediated by
      the beta 2 subtype, is enhanced, however, after therapy with atenolol relative to
      therapy with xamoterol.

PMID- 7504143
TI  - L-propionylcarnitine does not affect myocardial metabolic or functional response
      to chronotropic and inotropic stimulation after repetitive ischemia in
      anesthetized pigs.
AB  - In postischemic myocardium, fatty acid oxidation may be deficient owing to
      depletion of carnitine and citric acid cycle intermediates and fatty acylCoA
      induced inhibition of adenine nucleotide translocase. During postischemic stress,
      the impairment of the fatty acid oxidation may become more apparent. We therefore
      investigated in open-chest anesthetized pigs the effect of L-propionylcarnitine
      [100 mg/kg per day orally (p.o.) for 3 days and 50 mg/kg intravenously (i.v.) 2 h
      before the first occlusion; n = 13] on myocardial function and metabolism of
      postischemic (two cycles of 10-min occlusion each followed by 30-min reperfusion)
      myocardium under resting conditions and during chronotropic and inotropic
      stimulation with dobutamine. Myocardial levels of free carnitine were higher
      after pretreatment (5.7 +/- 1.4 vs. 4.0 +/- 1.3 mumol/g protein, p < 0.05). The
      ischemia-reperfusion-induced decreases in free carnitine were similar for both
      the untreated and treated animals, but in the latter free carnitine was not
      different from the baseline levels in the control animals. In untreated animals
      (n = 15), regional systolic segment shortening (SS) was 18.5 +/- 5.5% (means +/-
      SD) at baseline, but was reduced to 5.1 +/- 5.5% (p < 0.05) at the end of the
      second reperfusion period. Myocardial ATP levels had decreased by 30% (p < 0.05)
      in the presence of a maintained energy charge, while myocardial oxygen and
      lactate consumption had decreased to 61% and 9% of baseline, respectively. During
      subsequent i.v. infusion of dobutamine (2 micrograms/kg/min), SS and myocardial
      oxygen consumption per beat increased to 75 and 65% of baseline, respectively,
      whereas lactate consumption per beat increased to only 25% of baseline. Decreases
      in myocardial ATP and oxygen and lactate consumption were not different between
      treated and untreated animals. L-Propionylcarnitine-treated animals displayed
      slightly better postischemic recovery of systolic SS than did control animals; to
      39 and 28% (p = 0.056) of baseline, respectively, probably owing to a reduction
      in arterial blood pressure (BP), because L-propionylcarnitine prevented the
      increase in systemic vascular resistance produced by ischemia-reperfusion. L
      Propionylcarnitine did not affect myocardial metabolic and contractile functional
      responses to chronotropic and inotropic stimulation. In a model of repetitive
      myocardial ischemia, L-propionylcarnitine prevents systemic vasoconstriction in
      response to ischemia and reperfusion and, probably as a result of the lower
      afterload, slightly ameliorates postischemic hypofunction, but loss of carnitine
      apparently does not play a role in myocardial hypofunction after brief repetitive
      ischemia and reperfusion in pigs.

PMID- 7504144
TI  - Antiarrhythmic and hemodynamic effects of tropisetron in anesthetized rabbits.
AB  - Tropisetron (ICS 205-930) is a novel drug that blocks serotonin (5-HT3) receptors
      and, at higher concentrations, potassium channels. Programmed electrical
      stimulation (PES) and tracer microspheres were used to investigate
      antiarrhythmic, systemic, and regional hemodynamic effects in anesthetized
      rabbits. Tropisetron (0.3, 1, and 3 mg/kg intravenously, i.v.) dose-dependently
      increased the effective refractory period (ERP) to a first and similarly to a
      second extrastimulus. The arrhythmias elicited by PES with one and two
      extrastimuli were suppressed dose dependently. The same doses and a higher dose
      (6 mg/kg i.v.) were tested for systemic, especially cardiodepressant, and
      regional hemodynamic activity in a second series of experiments. Doses < or = 3
      mg/kg were almost devoid of systemic hemodynamic activity and did not alter the
      ECG. At the highest dose used (6 mg/kg), cardiodepression caused a decrease in
      blood pressure (BP), cardiac output (CO), and heart rate (HR) and an increase in
      central venous pressure (CVP). A selective increase in gastric blood flow was
      observed, starting at the lowest dose used. The highest cardiodepressant dose
      reversed this increase and decreased regional myocardial blood flow, especially
      to the subendocardial layer of the left ventricle, probably by lowering
      myocardial oxygen consumption. Antiarrhythmic effects thus start at 0.3 mg/kg,
      and doses < or = 3 mg/kg i.v. did not elicit hemodynamic side effects.

PMID- 7504145
TI  - Adenosine-5'-uronamides rapidly desensitize the adenosine A2 receptor in coronary
      artery.
AB  - This study examined the structure-activity-relationship (SAR) of adenosine
      analogs and their ability to induce tachyphylaxis in vascular smooth muscle.
      Adenosine-5'-uronamides,5'-N-ethylcarboxamidoadenosine (NECA), 5'-N
      cyclopropylcarboxamidoadenosine (CPCA), and 2-[p-(2-carboxyethyl)phenethylamino]
      5'-N-ethylcarboxamidoadenosin e (CGS 21680), evidenced rapid desensitization of
      the A2 vasorelaxant response in porcine coronary artery in vitro whereas
      adenosine, 2-chloroadenosine (CAD), or 2-[(2-cyclohexylethyl)-amino]adenosine
      (CGS 22492) failed to do so. Tissues with prior exposure to NECA exhibited
      mitigated relaxation responses to adenosine, CAD, and NECA but not to
      isoproterenol, forskolin, pinacidil, or sodium nitroprusside (SNP). The data
      suggest that adenosine-5'-uronamides homologously desensitize the A2 receptor in
      porcine coronary artery smooth muscle.

PMID- 7504146
TI  - Prostacyclin contributes to nitroglycerin-mediated relaxation of human umbilical
      arteries.
AB  - This study compared the action of nitroglycerin (GTN) and linsidomine (SIN-1) on
      vessel tone and prostacyclin (PGI2) production of human umbilical arteries in
      vitro. GTN-induced vessel relaxation was significantly attenuated by indomethacin
      pretreatment. This was associated with a significant inhibition of the fourfold
      stimulation of PGI2 release by GTN. No such effects were seen with SIN-1. We
      concluded that GTN-induced PGI2 release contributed to the vasodilatory action of
      organic nitrates in the fetoplacental circulation.

PMID- 7504147
TI  - Why some fitness landscapes are fractal.
AB  - Many biological and biochemical measurements, for example the "fitness" of a
      particular genome, or the binding affinity to a particular substrate, can be
      treated as a "fitness landscape", an assignment of numerical values to points in
      sequence space (or some other configuration space). As an alternative to the
      enormous amount of data required to completely describe such a landscape, we
      propose a statistical characterization, based on the properties of a random walk
      through the landscape and, more specifically, its autocorrelation function. Under
      assumptions roughly satisfied by two classes of simple model landscapes (the N-k
      model and the p-spin model) and by the landscape of estimated free energies of
      RNA secondary structures, this autocorrelation function, along with the mean and
      variance of individual points and the size of the landscape, completely
      characterize it. Having noted that these and other landscapes of estimated
      replication and degradation rates all have a well-defined correlation length, we
      propose a classification of landscapes depending on how the correlation length
      scales with the diameter of the landscape. The landscapes of some of the kinetic
      parameters of RNA molecules scale similarly to the model landscapes introduced
      into evolutionary studies from other fields, such as quadratic spin glasses and
      the traveling salesman problem, but the correlation length of RNA landscapes are
      considerably smaller. Nevertheless, both the model and some of the RNA landscapes
      satisfy a test of self-similarity proposed by Sorkin (1988).

PMID- 7504149
TI  - Calculation of contributions of individual monomeric units to biopolymer
      function.
AB  - The possibility of determination of individual monomeric unit contributions into
      biopolymer function based on the data on biopolymer primary structures and
      functional activities is discussed. We show that even the most complete set of
      data do not allow to determine the absolute contributions of monomeric units,
      while their relative contributions may be determined.

PMID- 7504148
TI  - The binomial distribution and the evidence for independent action of ion
      channels.
AB  - Calculations are presented demonstrating a class of hypothetical channel
      interactions which cannot be recognized by means of the commonly used binomial
      test. On the contrary, ion channels which interact in such a way will be
      identified with the help of the binomial test as independent. Thus, the binomial
      test cannot be used to prove the absence of interactions. Furthermore, in cases
      in which existing interactions are recognized by the binomial test, estimation of
      the strength of the interactions may be inaccurate.

PMID- 7504150
TI  - Detection of P glycoprotein activity on normal and leukemic CD34+ cells.
AB  - Rhodamine 123 is transported by the transmembrane efflux pump P glycoprotein
      (Pgp). We used this fluorescent dye to study multidrug resistance (MDR) activity
      in normal and leukemic CD34+ cells. These immature cells had a high degree of MDR
      activity. Among leukemic cells, CD34+ leukemias had significantly higher MDR
      activity as compared to CD34- leukemias. Heterogeneous results in cell
      subpopulations, however, indicate that prognosis should be interpreted in the
      light of MDR analysis.

PMID- 7504151
TI  - Inhibition of granulocytic differentiation of acute promyelocytic leukemia cells
      in primary culture by transforming growth factor-beta.
AB  - We investigated the effect of transforming growth factor-beta 1 (TGF beta) on the
      proliferation and differentiation of cultured acute promyelocytic leukemia (APL)
      cells with the chromosomal t(15;17) translocation obtained from four patients to
      determine the role of TGF beta on growth and differentiation of APL cells. DNA
      synthesis, determined by 3H-thymidine uptake, was inhibited in the presence and
      absence of granulocyte colony-stimulating factor (G-CSF) in a dose-dependent
      manner by TGF beta in APL cells obtained from three of the four cases. TGF beta
      and G-CSF did not significantly affect the differentiation of APL cells, but all
      trans retinoic acid (RA) induced morphological and functional differentiation in
      all APL cells tested. G-CSF markedly enhanced RA-induced granulocytic
      differentiation in APL cells obtained from all four cases. In cells in which TGF
      beta inhibited DNA synthesis, it also inhibited RA-induced granulocytic
      differentiation of APL cells and, to a greater degree, granulocytic
      differentiation induced by RA plus G-CSF. These results suggest that TGF beta is
      a negative regulator of the proliferation and differentiation of APL cells. The
      significance of TGF beta as an endogenous regulator in differentiation therapy
      with RA of APL patients is discussed.

PMID- 7504152
TI  - Sustained c-kit expression in a human erythroleukemia cell line (HEL) after
      megakaryocytic differentiation induced by 12-O-tetradecanoylphorbol-13-acetate
      (TPA).
AB  - Changes in c-kit proto-oncogene expression were examined in a human
      erythroleukemia cell line, HEL, during 12-O-tetradecanoylphorbol 13-acetate (TPA)
      induced megakaryocytic differentiation. When HEL cells were treated with 10(-7) M
      TPA, glycophorin A expression and hemoglobin synthesis were reduced, while the
      expression of GP IIb/IIIa was induced in association with the morphological
      changes. Northern blot analysis showed that, during this megakaryocytic
      differentiation of HEL cells, c-kit mRNA expression persisted even after there
      was an apparent reduction in c-myc mRNA. This finding supports the idea that the
      expression of c-kit, a marker of primitive hematopoietic progenitors, may persist
      along with differentiation toward a megakaryocytic lineage.

PMID- 7504153
TI  - Adverse reaction reporting and new antipsychotics.

PMID- 7504155
TI  - G-CSF levels during spontaneous recovery from drug-induced agranulocytosis.

PMID- 7504154
TI  - Effect of growth hormone on brain neurotransmitters.

PMID- 7504156
TI  - Using role-plays to teach palliative medicine.
AB  - Teaching of communication skills in Palliative Medicine can be achieved using a
      three hour exercise involving role-plays, a time of feedback and discussion, a
      teaching video and a reading list. Using this teaching method self-ratings of
      perceived skills recorded on a questionnaire before and four weeks after the
      exercises showed a significant increase in both undergraduates and postgraduates.
      The validity of these self-ratings as a tool to measure communication skills was
      assessed by correlating the self-ratings with the ratings given by the
      participant and the observers after the clinical scenarios from the questionnaire
      were simulated in role-plays.

PMID- 7504157
TI  - Isolation of Pseudomonas cepacia in cystic fibrosis patient.
AB  - Pulmonary infection on cystic fibrosis (CF) patients are associated with a
      limited qualitative number of microorganisms. During the colonization process,
      Staphylococcus aureus usually precedes Pseudomonas aeruginosa. This latter is at
      first non-mucoid, being replaced or associated to a mucoid morphotype which is
      rare in other diseases. In 1980, Pseudomonas cepacia appeared as an important
      agent in CF pulmonary infections with a mean frequency of about 6.1% isolations
      in different parts of the world. The primus colonization mainly occurs in the
      presence of pre-existent tissue lesions and the clinical progress of the disease
      is variable. In some patients it can be fulminant; in others it can cause a
      gradual and slow decrease in their pulmonary functions. The concern with this
      germ isolation is justified by its antibiotic multiple resistance and the
      possibility of direct transmission from a colonized patient to a non-colonized
      one. We reported the first case of P. cepacia infection in a CF patient in our
      area. The microbiological attendance to this patient had been made from 1986 to
      1991 and the first positive culture appeared in 1988. The sensitivity profile
      showed that the primus colonization strain was sensitive to 9 of 17 tested
      antibiotics, however in the last culture the strain was resistant to all
      antibiotics. These data corroborate the need for monitoring the bacterial flora
      on CF patients respiratory system.

PMID- 7504158
TI  - Three-dimensional confocal light microscopy of neurons: fluorescent and
      reflection stains.

PMID- 7504159
TI  - Assay of vesicle motility in squid axoplasm.
AB  - Axoplasm prepared as described above will maintain high levels of fast axonal
      transport for 1-2 hours, although moderate decrements in the average velocity may
      be noted over time. The organelles and structures that can be detected in
      isolated axoplasma are as small as the 50-nm synaptic vesicles or 25-nm
      microtubules, well below the limits of resolution for light microscopy; however,
      in the center of the axoplasm, where the density of structures is high,
      individual microtubules are not readily distinguished and individual vesicles can
      be followed only for short distances before they move out of the plane of focus
      or are lost in the multitude of neighboring organelles. On the periphery of
      perfused axoplasm, each of these structures may be readily detected and analyzed,
      but some information is lost about the role of specific axoplasmic organization
      in normal transport processes. Fortunately, the juxtaposition in one preparation
      of essentially structurally intact axoplasm with the extracted individual
      microtubules transporting organelles provides a unique preparation for molecular
      dissection of intracellular transport (Brady et al., 1985).

PMID- 7504160
TI  - Microscopic visualization of the retina by angiography with high-molecular-weight
      fluorescein-labeled dextrans in the mouse.
AB  - Methods currently available for the examination of the retinal vasculature of
      laboratory animals have significant drawbacks. Fluorescein angiography of rodent
      eyes is hampered by a poor view of the peripheral retina and difficulty in
      performing fundus photography. Methods of staining or filling retinal vessels are
      unreliable, labor-intensive, or have high backgrounds. We have developed a novel
      technique that is quick, simple, and accurate. Fluorescein-labeled 2 million
      molecular weight dextrans are used to fill the retinal vasculature of mice in
      vivo, followed by removal of the retina, fixation in paraformaldehyde, and
      examination of the vascular pattern in whole mount preparations by fluorescence
      microscopy. We found that fluorescein and fluorescein-labeled low-molecular
      weight dextrans (40,000-500,000) are not suitable as they leak out of the
      vasculature to stain the entire retina in whole mount preparations. By contrast,
      fluorescein-labeled 2 million molecular weight dextrans remain in the vasculature
      for many months without diffusion or decay. Under low magnification, the entire
      retinal vasculature can be visualized at one time. By focusing from one plane to
      another, the superficial, connecting, or deep vascular layers are delineated. The
      background fluorescence is very low. We have successfully used this technique in
      over 20 mice per day to document retinal angiogenesis in a model of oxygen
      induced proliferative retinopathy.

PMID- 7504161
TI  - Uptake of metabolites by postcapillary venules: mechanism for the control of
      arteriolar diameter.

PMID- 7504162
TI  - Isolation of rfb gene clusters directing the synthesis of O polysaccharides
      consisting of mannose homopolymers and serological analysis of
      lipopolysaccharides.
AB  - Four serotypes of two genera, Escherichia coli O8 and O9 and Klebsiella O3 and
      O5, produce the O polysaccharides consisting of mannose homopolymers. Previously,
      we reported the isolation and expression of E. coli O9 rfb in E. coli K-12
      strains (Kido et al, J. Bacteriol., 171: 3629-3633, 1989). In this study, R'
      plasmids carrying his-rfb region of the other three strains were isolated and
      expressed in E. coli K-12 strain. Serological study of lipopolysaccharides (LPS)
      synthesized in E. coli K-12 strain was carried out. His-linked rfb genes from E.
      coli O9 and Klebsiella O3 directed the synthesis of O polysaccharides with the
      same antigenicity as those of the parental strains in E. coli K-12 strain. On the
      other hand, rfb genes from E. coli O8 and Klebsiella O5 directed the synthesis of
      O polysaccharides which were antigenically not identical but partially common to
      those of the parental strains. A rough strain derived from E. coli O8 synthesized
      LPS which showed the identical antigenicity as the wild strain when the his-rfb
      region of E. coli O8 was introduced. The results suggest that some genes located
      distantly from his are additionally required to complete the synthesis of O
      polysaccharides of E. coli O8 and Klebsiella O5.

PMID- 7504163
TI  - Functional and phenotypical analysis of subsets of rat CD4+ T cells.
AB  - Rat CD4+ T cells were divided into two distinct subsets by a monoclonal antibody
      RTH-1 recognizing a unique epitope on rat CD45R. Cellular distribution of OX-22-
      and RTH-1-defined antigens was the same. However, OX-22 and RTH-1 recognized
      different epitopes that exist on rat CD45R. The expression of IL-4 gene was
      detected only in RTH-1low CD4+ T cell subset upon various stimulations. In
      contrast, the expression of IL-2 and IFN-gamma gene varied depending upon the
      nature of stimuli. The increased cell surface expression of CD44 was detected in
      RTH-1high CD4+ T cell subset. Conversely the increased expression of CD2 was
      detected in RTH-1low CD4+ T cell subset. The expression of CD3 and LFA-1 was not
      significantly different between RTH-1high and RTH-1low subsets.

PMID- 7504164
TI  - Structural domains in chondroitin sulfate identified by anti-chondroitin sulfate
      monoclonal antibodies. Immunosequencing of chondroitin sulfates.
AB  - Monoclonal antibodies have been developed that recognize epitopes in native
      chondroitin sulfate chains. One of these antibodies, CS-56, reportedly recognizes
      chondroitin 4- and 6-sulfates. However, this antibody, and four other anti
      chondroitin sulfate antibodies, 4C3, 4D3, 6C3 and 7D4, do not recognize epitopes
      in chondroitin sulfate chains from Swarm rat chondrosarcoma proteoglycan, an
      indication that native chondroitin sulfate epitopes are more structurally complex
      than the standard 0-, 4-, and 6-sulfated disaccharide repeats that constitute the
      backbone of chondroitin sulfate chains. A series of limited chondroitinase
      digestions was performed on the large aggregating proteoglycan monomer extracted
      from embryonic chick chondrocyte cultures to identify the digestion parameters
      required to release the different native chondroitin sulfate epitopes. Some
      epitopes were more accessible to enzymatic digestion than other epitopes. The
      approximate location of epitopes was determined by measuring the size of
      undigested oligosaccharides retained on the core protein following a limited
      digestion, and correlating this with the level of immunoreactivity for the
      different antibodies. These analyses identified the locations of three different
      antigenic domains. Domain 1 resides at the linkage region and contains epitopes
      for two of the five antibodies, and a portion of the epitopes for a third
      antibody. Domain 2 lies in the interior of the chain and contains epitopes for
      three of the five antibodies. Domain 3 resides at the non-reducing terminus and
      does not contain epitopes for any of the anti-chondroitin sulfate antibodies used
      in this study. These results indicate that specific native chondroitin sulfate
      epitopes are non-randomly distributed within the linear framework of chondroitin
      sulfate chains.

PMID- 7504165
TI  - A radioimmunoassay for the N-terminal propeptide of rat procollagen type III.
      Application to the study of the uptake of the N-terminal propeptide of
      procollagen type III in isolated perfused rat liver.
AB  - Antibodies against a synthetic peptide representing the 14 C-terminal amino acids
      of the N-terminal propeptide of rat and bovine procollagen type III were raised
      in rabbits and used to develop a radioimmunoassay. N-Terminal propeptide of
      procollagen type III, purified from calf skin, served as standard and tracer
      material. The IC50 of the standard inhibition curve was 2.1 micrograms/l, the
      lower limit of detection about 0.4 microgram/l, interassay variation was 8.5% and
      the intraassay variation 6.6% in typical experiments. Three peaks of antigenicity
      were detected in rat serum after gel chromatography. One peak coeluted with
      purified N-terminal propeptide of procollagen type III, one peak contained
      material approximately twice this size, and one peak eluted close to the void
      volume of the column. The antigen concentration in rat serum decreased in an age
      dependent manner. Rat, bovine, sheep and minipig serum antigen was sufficiently
      crossreactive to allow the application of the assay to these species, whereas
      human, goat and guinea pig samples were not. The degradation product Col 1,
      causing non-parallel inhibition in commercially available assays for human
      samples was not recognized since it does not contain the epitope represented by
      the synthetic peptide. The assay was used to study the half-life of bovine and
      endogenous N-terminal propeptide of procollagen type III in isolated perfused rat
      liver. [125I]-labeled antigen was cleared rapidly from the perfusate (t1/2 less
      than 5 min). The bovine antigen was removed from the perfusate with a half-life
      of 15 +/- 4 min. Endogenous propeptide was perfused for 120 min with little
      change in concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504167
TI  - Physostigmine block of ion channels activated by acetylcholine in BC3H1 cells.
AB  - Single-channel recording techniques have been used to study the effects of
      physostigmine on the kinetics of ion channels activated by acetylcholine in BC3H1
      mouse tumor cells grown in culture. Physostigmine reduced mean channel open time,
      with 50% reduction occurring at about 7 microM physostigmine. Although openings
      did not appear to occur in bursts, channel closed-time distributions exhibited a
      new component 7-8 msec in duration. The area of this component, but not its time
      constant, increased with higher concentrations of physostigmine. Results are
      consistent with a simple sequential channel-blocking model in which the new
      closed-time component represents a blocked state of the channel. Membrane
      hyperpolarization increased the potency of physostigmine in reducing channel open
      time and also prolonged the duration of the blocked state. The voltage dependence
      of physostigmine block was unexpected, because physostigmine is uncharged at
      physiological pH.

PMID- 7504168
TI  - The effects of isoflurane on acetylcholine receptor channels.: 2. Currents
      elicited by rapid perfusion of acetylcholine.
AB  - We studied the effects of the volatile anesthetic isoflurane on nicotinic
      acetylcholine (ACh) receptor channels using a technique for rapid perfusion of
      ACh to outside-out patches. Channels were activated by ACh, at concentrations
      ranging from 1 microM to 10 mM, and the macroscopic current flowing through tens
      or hundreds of channels was measured. Isoflurane reduced the peak current
      response to saturating concentrations of ACh, increased the current decay rate
      due to desensitization, and decreased the rate of recovery from desensitization.
      The effect of isoflurane on peak currents was concentration dependent; at 2%
      isoflurane, the peak current was reduced by half. The effect of isoflurane on the
      peak current induced by nonsaturating concentrations of ACh was smaller. We
      measured the onset and recovery of current inhibition by isoflurane, by rapidly
      applying and removing isoflurane to the patch within 100 microseconds. 2%
      isoflurane, currents were inhibited with a time constant of 200-300 microseconds
      and recovered with a time constant of 500-700 microseconds. We interpreted our
      results in terms of a kinetic model in which isoflurane binds directly to both
      open and closed channels (not necessarily within the pore of the channel) and
      stops the flow of ions through open channels. This model provides a quantitative
      explanation for the kinetic and equilibrium effects of isoflurane on peak
      currents activated by saturating concentrations of ACh. Our data support the idea
      that the flickering effect of isoflurane on single ACh receptor channels is
      caused by rapid binding and dissociation of isoflurane to an inhibitory binding
      site on the protein. The effects of isoflurane on the apparent affinity of ACh
      and on desensitization are not predicted by the model. These effects may arise
      from the binding of isoflurane to other sites, not necessarily on the protein
      itself.

PMID- 7504169
TI  - [The hierarchy of complexes and compact structures of trivaline with nucleic
      acids. II. Interaction of trivaline with single-stranded RNA (using poly(U) as an
      example)].
AB  - It has been shown by equilibrium dialysis that at a poly(U) concentration above
      the "critical" one, the complete polymer saturation with trivaline reaches
      approximately 0.7, i.e., in these conditions the peptide dimer occupied on
      poly(U) a site of three bases in length. It has been shown by flow linear
      dichroism that trivaline beta-dimers preferentially binding with the single
      stranded polymer rather than with the double-stranded one. It has been shown by
      electron microscopy that "the highest" compact structure of trivaline-poly(C)
      consists of dozens of "biduplex" structures. Beginning with a dimer trivaline
      poly(U) complex, we proposed a schematic model for other complexes and compact
      structures of these molecules.

PMID- 7504170
TI  - [Antigenic determinants of proteins. The humoral immune response].
AB  - There exist two opposing points of view on the organization of antigenic
      determinants of proteins: 1) the determinants are stringently predetermined
      regions of the protein molecule; 2) all the surface of the protein globule is
      potentially antigenic, and the immune response is generated occasionally in every
      individual, although some sites of the protein surface could be preferable for
      eliciting the immune response. In this work, taking into account the results of
      recent investigations, we propose some reconciliation: a correlation between the
      rigidity of the protein architecture and the antigenicity of the particular sites
      of the antigen molecule. Some general principles of the antigenic determinants of
      proteins are formulated.

PMID- 7504171
TI  - Binding of the Src SH2 domain to phosphopeptides is determined by residues in
      both the SH2 domain and the phosphopeptides.
AB  - Src homology 2 (SH2) domains are found in a variety of signaling proteins and
      bind phosphotyrosine-containing peptide sequences. To explore the binding
      properties of the SH2 domain of the Src protein kinase, we used immobilized
      phosphopeptides to bind purified glutathione S-transferase-Src SH2 fusion
      proteins. With this assay, as well as a free-peptide competition assay, we have
      estimated the affinities of the Src SH2 domain for various phosphopeptides
      relative to a Src SH2-phosphopeptide interaction whose Kd has been determined
      previously (YEEI-P; Kd = 4 nM). Two Src-derived phosphopeptides, one containing
      the regulatory C-terminal Tyr-527 and another containing the autophosphorylation
      site Tyr-416, bind the Src SH2 domain in a specific though low-affinity manner
      (with about 10(4)-lower affinity than the YEEI-P peptide). A platelet-derived
      growth factor receptor (PDGF-R) phosphopeptide containing Tyr-857 does not bind
      appreciably to the Src SH2 domain, suggesting it is not the PDGF-R binding site
      for Src as previously reported. However, another PDGF-R-derived phosphopeptide
      containing Tyr-751 does bind the Src SH2 domain (with an affinity approximately 2
      orders of magnitude lower than that of YEEI-P). All of the phosphopeptides which
      bind to the Src SH2 domain contain a glutamic acid at position -3 or -4 with
      respect to phosphotyrosine; changing this residue to alanine greatly diminishes
      binding. We have also tested Src SH2 mutants for their binding properties and
      have interpreted our results in light of the recent crystal structure solution
      for the Src SH2 domain. Mutations in various conserved and nonconserved residues
      (R155A, R155K, N198E, H201R, and H201L) cause slight reductions in binding, while
      two mutations cause severe reductions. The W148E mutant domain, which alters the
      invariant tryptophan that marks the N-terminal border of the SH2 domain, binds
      poorly to phosphopeptides. Inclusion of the SH3 domain in the fusion protein
      partially restores the binding by the W148E mutant. A change in the invariant
      arginine that coordinates twice with phosphotyrosine in the peptide (R175L)
      results in a nearly complete loss of binding. The R175L mutant does display high
      affinity for the PDGF-R peptide containing Tyr-751, via an interaction that is at
      least partly phosphotyrosine independent. We have used this interaction to show
      that the R175L mutation also disrupts the intramolecular interaction between the
      Src SH2 domain and the phosphorylated C terminus within the context of the entire
      Src protein; thus, the binding properties observed for mutant domains in an in
      vitro assay appear to mimic those that occur in vivo.

PMID- 7504172
TI  - A 31-amino-acid N-terminal extension regulates c-Crk binding to tyrosine
      phosphorylated proteins.
AB  - Overproduction of v-Crk, but not of c-Crk, in chicken embryo fibroblasts results
      in cell transformation. The transforming activity of v-Crk mutants correlates
      with their ability to cause increased tyrosine phosphorylation of specific
      cellular proteins, a property that depends on the binding of v-Crk to
      phosphotyrosine residues via its SH2 domain. In this study, proteins translated
      in rabbit reticulocyte lysates were used to analyze interactions between Crk
      derivatives and tyrosine-phosphorylated proteins, particularly the epidermal
      growth factor (EGF) receptor. The results demonstrate that the binding affinity
      of c-Crk is much lower than that of v-Crk, despite the fact that both proteins
      contain identical SH2 domains. Moreover, a 31-amino-acid N-terminal extension of
      c-Crk, resulting from upstream translational initiation at a CUG codon,
      significantly increases the ability of the resulting protein to bind to
      phosphotyrosine-containing proteins. Of those 31 amino acids, 24 can be found in
      the 27-amino-acid region between Gag and Crk sequences in v-Crk, and removal of
      this region results in a protein with lower affinity toward the EGF receptor. In
      addition, fusion of Gag to the amino terminus of c-Crk yields a protein with a
      binding activity that is lower than that of v-Crk but significantly higher than
      that of c-Crk without the fusion. These data suggest that sequences N terminal to
      the Crk SH2 regulate binding activity to tyrosine-phosphorylated proteins and
      that the amino acids encoded immediately 5' to the c-Crk initiator AUG
      specifically increase binding affinity. In contrast, deletion of one or two SH3
      domains of c-Crk proteins did not change their affinity for the EGF receptor.
      These results were confirmed in vivo by using A431-derived cell lines
      overproducing either the chicken c-Crk protein or c-Crk with the 31-amino-acid N
      terminal extension. Furthermore, the in vivo experiments suggest that binding of
      Crk proteins to the stimulated EGF receptor results in Crk phosphorylation and
      subsequent loss of binding affinity.

PMID- 7504173
TI  - Inactive chromatin spreads from a focus of methylation.
AB  - The detailed mechanisms of inhibition of transcription by DNA methylation are
      still unknown, but it has become obvious that the formation of chromatin plays an
      important role in this process. Using an approach enabling us to methylate, in
      vitro, chosen regions in a plasmid, we now show that specific methylation of
      nonpromoter sequences results in transcriptional inhibition of a reporter gene
      construct and that this inhibition is independent of the position of the
      methylated region within the plasmid. In plasmid minichromosomes containing a
      short region of methylated DNA, both methylated and unmethylated sequences are
      protected from limited MspI digestion. Our results show that inactive chromatin
      is present at unmethylated regions in partially methylated minichromosomes and
      can thereby inhibit gene expression. Spreading of the inactive chromatin is not
      inhibited by the presence of active promoters, nor is it a consequence of
      transcriptional inactivity.

PMID- 7504166
TI  - Genetics of lipopolysaccharide biosynthesis in enteric bacteria.
AB  - From a historical perspective, the study of both the biochemistry and the
      genetics of lipopolysaccharide (LPS) synthesis began with the enteric bacteria.
      These organisms have again come to the forefront as the blocks of genes involved
      in LPS synthesis have been sequenced and analyzed. A number of new and
      unanticipated genes were found in these clusters, indicating a complexity of the
      biochemical pathways which was not predicted from the older studies. One of the
      most dramatic areas of LPS research has been the elucidation of the lipid A
      biosynthetic pathway. Four of the genes in this pathway have now been identified
      and sequenced, and three of them are located in a complex operon which also
      contains genes involved in DNA and phospholipid synthesis. The rfa gene cluster,
      which contains many of the genes for LPS core synthesis, includes at least 17
      genes. One of the remarkable findings in this cluster is a group of several genes
      which appear to be involved in the synthesis of alternate rough core species
      which are modified so that they cannot be acceptors for O-specific
      polysaccharides. The rfb gene clusters which encode O-antigen synthesis have been
      sequenced from a number of serotypes and exhibit the genetic polymorphism
      anticipated on the basis of the chemical complexity of the O antigens. These
      clusters appear to have originated by the exchange of blocks of genes among
      ancestral organisms. Among the large number of LPS genes which have now been
      sequenced from these rfa and rfb clusters, there are none which encode proteins
      that appear to be secreted across the cytoplasmic membrane and surprisingly few
      which encode integral membrane proteins or proteins with extensive hydrophobic
      domains. These data, together with sequence comparison and complementation
      experiments across strain and species lines, suggest that the LPS biosynthetic
      enzymes may be organized into clusters on the inner surface of the cytoplasmic
      membrane which are organized around a few key membrane proteins.

PMID- 7504174
TI  - The SH3 domain of p56lck is involved in binding to phosphatidylinositol 3'-kinase
      from T lymphocytes.
AB  - Many of the Src-like tyrosine kinases are thought to participate in multiprotein
      complexes that modulate transmembrane signalling through tyrosine
      phosphorylation. We have used in vitro binding studies employing bacterially
      expressed glutathione S-transferase-p56lck fusion proteins and cell extracts to
      map regions on p56lck that are involved in binding to phosphatidylinositol 3'
      kinase (PI3K). Deletions within the SH3 domain of p56lck abolished binding of
      PI3K activity from T-cell lysates, whereas deletion of the SH2 domain caused only
      a slight reduction in the level of PI3K activity bound to p56lck sequences. The
      binding of PI3K from T-cell extracts to p56lck was not blocked by
      antiphosphotyrosine antibodies, but p56lck-bound PI3K activity was sensitive to
      phosphatase treatment. The SH3 domain of p56lck also bound the majority of PI3K
      activity from uninfected chicken embryo fibroblasts. However, a drastically
      different binding specificity was observed with use of extracts of Rous sarcoma
      virus v-src-transformed cells, in which the majority of PI3K activity bound to
      the SH2 domain of p56lck in a phosphotyrosine-dependent manner. These results
      suggest that are two modes of PI3K binding to p56lck, and presumably to other Src
      like tyrosine kinases. In one mode, PI3K from T cells or uninfected chicken
      embryo fibroblasts binds predominantly to the SH3 domain of p56lck. In the other
      mode, involving PI3K from Rous sarcoma virus-transformed cells, binding is
      largely phosphotyrosine dependent and requires the SH2 domain of p56lck.

PMID- 7504175
TI  - Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1.
AB  - IRS-1 (insulin receptor substrate 1) is a principal insulin receptor substrate
      that undergoes tyrosine phosphorylation during insulin stimulation. It contains
      over 20 potential tyrosine phosphorylation sites, and we suspect that multiple
      insulin signals are enabled when the activated insulin receptor kinase
      phosphorylates several of them. Tyrosine-phosphorylated IRS-1 binds specifically
      to various cellular proteins containing Src homology 2 (SH2) domains (SH2
      proteins). We identified some of the tyrosine residues of IRS-1 that undergo
      insulin-stimulated phosphorylation by the purified insulin receptor and in intact
      cells during insulin stimulation. Automated sequencing and manual radiosequencing
      revealed the phosphorylation of tyrosine residues 460, 608, 628, 895, 939, 987,
      1172, and 1222; additional sites remain to be identified. Immobilized SH2 domains
      from the 85-kDa regulatory subunit (p85 alpha) of the phosphatidylinositol 3'
      kinase bind preferentially to tryptic phosphopeptides containing Tyr(P)-608 and
      Tyr(P)-939. By contrast, the SH2 domain in GRB2 and the amino-terminal SH2 domain
      in SHPTP2 (Syp) specifically bind to Tyr(P)-895 and Tyr(P)-1172, respectively.
      These results confirm the p85 alpha recognizes YMXM motifs and suggest that GRB2
      prefers a phosphorylated YVNI motif, whereas SHPTP2 (Syp) binds to a
      phosphorylated YIDL motif. These results extend the notion that IRS-1 is a
      multisite docking protein that engages various downstream regulatory elements
      during insulin signal transmission.

PMID- 7504176
TI  - Transformation by Fos proteins requires a C-terminal transactivation domain.
AB  - The Fos family of proteins now includes seven members: the retroviral proteins
      FBR-v-Fos and FBJ-v-Fos and the cellular proteins c-Fos, FosB, FosB2, Fra1, and
      Fra2. Four proteins (FBR-v-Fos, FBJ-v-Fos, c-Fos, and FosB) transform established
      rodent fibroblast cell lines, while three (FosB2, Fra1, and Fra2) do not. As all
      family members display sequence-specific DNA-binding activity as part of a
      heterodimeric complex with Jun proteins, other features must account for the
      differences in transforming potential. We demonstrate here that all transforming
      members have a C-terminal transactivation domain that is lacking in
      nontransforming members. The nontransforming proteins Fra1 and Fra2 can be
      converted to transforming proteins by fusion of a transactivation domain from
      either FosB or VP16. We also demonstrate that differences in the basic region
      leucine zipper domain affecting either the affinity or sequence specificity of
      DNA binding are not determinants of the difference in transforming potential
      among members of the Fos family. The results further define the functional
      requirements for transformation by Fos proteins and suggest that the subunit
      composition of AP1 complexes is an important determinant of mitogenic signalling
      capability.

PMID- 7504179
TI  - Genomic structure and regulation of the promoter of the rat insulin-like growth
      factor binding protein-2 gene.
AB  - We describe the complete genomic organization of the rat insulin-like growth
      factor binding protein-2 (rIGFBP-2) gene. This single-copy gene spans over 36
      kilobases (kb) and is split into four exons of 475, 224, 141, and 472 nucleotides
      (nt), and three introns of 32 kb, 686, and 1793 nt, respectively. A single
      transcription start site (-90) was mapped by S1 protection assay and primer
      extension. The putative promoter of the rIGFBP-2 gene does not possess TATA or
      CAAT elements; however, it contains three GC-rich regions located 37, 57, and 81
      nt 5' of the cap site. Deletion analysis of the 0.6-kb region of the upstream
      sequences and transfection of these constructs into BRL-3A and Chinese hamster
      ovary cells were used to localize possible cis-acting elements. The three GC
      boxes enhanced chloramphenicol acetyltransferase and luciferase transcription
      almost to the same level as the XbaI-NsphI (-579 to +1) fragment and displayed
      synergism and orientation dependence. In addition a similar positive effect on
      luciferase transcription has been obtained by cotransfecting these fragments with
      varying amounts of Sp1 expression vector into Drosophila cells that lack
      endogenous Sp1. In vitro gel mobility shift assays demonstrated that box 1
      (GGGCGG), box 2 (GGGAGG), and box 3 (GGGAAGG) bind to SpI with variable
      affinities and display cooperativity. A protein that gave a similar DNA binding
      pattern was present in nuclear extracts of BRL-3A cells. To analysis using
      consensus or aberrant Sp1 elements and a polyclonal Sp1 antiserum to inhibit DNA
      binding were performed. These in vivo and in vitro data demonstrated that Sp1
      plays an important role in the regulation of the expression of rIGFBP-2.

PMID- 7504180
TI  - Abnormally high incidence of SCE in three successive cell cycles in the CHO
      mutant EM9 as detected by a three-way immunoperoxidase differential staining.
AB  - A high resolution three-way immunoperoxidase method for the detection of SCE per
      cell generation in chromosomes with very low levels of BrdU in DNA has been
      recently standardized in our laboratory. We have made use of this methodology to
      assess whether the CHO mutant EM9 is solely hypersensitive to BrdU incorporated
      into template DNA as regards the extraordinarily high SCE frequency observed as
      compared with its parental line, AA8, or also shows an elevated spontaneous
      frequency of exchanges. Our results confirm the importance of BrdU incorporated
      for SCE in EM9 but also show that the estimated yield of spontaneous SCE is about
      10 times higher in this mutant than in the parental line, AA8.

PMID- 7504177
TI  - Thyroid hormone receptor can modulate retinoic acid-mediated axis formation in
      frog embryogenesis.
AB  - Thyroid hormone receptor acts as a hormone-dependent transcriptional
      transactivator and as a transcriptional repressor in the absence of thyroid
      hormone. Specifically, thyroid hormone receptor can repress retinoic acid-induced
      gene expression through interactions with retinoic acid receptor. (Retinoic acid
      is a potent teratogen in the frog Xenopus laevis, acting at early embryonic
      stages to interfere with the formation of anterior structures. Endogenous
      retinoic acid is thought to act in normal anterior-posterior axis formation.) We
      have previously shown that thyroid hormone receptor RNA (alpha isotype) is
      expressed and polysome-associated during Xenopus embryogenesis preceding thyroid
      gland maturation and endogenous thyroid hormone production (D. E. Banker, J.
      Bigler, and R. N. Eisenman, Mol. Cell. Biol. 11:5079-5089, 1991). To determine
      whether thyroid hormone receptor might influence the effects of retinoic acid in
      early frog development, we have examined the results of ectopic thyroid hormone
      receptor expression on retinoic acid teratogenesis. We demonstrate that
      microinjections of full-length thyroid hormone receptor RNA protect injected
      embryos from retinoic acid teratogenesis. DNA binding is apparently essential to
      this protective function, as truncated thyroid hormone receptors, lacking DNA
      binding domains but including hormone-binding and dimerization domains, do not
      protect from retinoic acid. We have shown that microinjections of these dominant
      interfering thyroid hormone receptors, as well as anti-thyroid hormone receptor
      antibodies, increase retinoic acid teratogenesis in injected embryos, presumably
      by inactivating endogenous thyroid hormone receptor. This finding suggests that
      endogenous thyroid hormone receptors may act to limit retinoic acid sensitivity.
      On the other hand, after thyroid hormone treatment, ectopic thyroid hormone
      receptor mediates teratogenesis that is indistinguishable from the dorsoanterior
      deficiencies produced in retinoic acid teratogenesis. The previously
      characterized retinoic acid-responsive gene, Xhox.lab2, can be induced by thyroid
      hormone in embryos ectopically expressing thyroid hormone receptor and is less
      responsive to retinoic acid in such embryos. The fact that both thyroid hormone
      and retinoic acid can affect overlapping gene expression pathways to produce
      abnormal embryonic axes and can regulate the same early-expressed gene suggests a
      model in which thyroid hormone receptor blocks retinoic acid receptor-mediated
      teratogenesis by directly repressing retinoic acid-responsive genes.

PMID- 7504181
TI  - An assessment of the in vitro hepatocyte micronucleus assay.
AB  - The in vitro hepatocyte micronucleus assay was tested for its practicability and
      its usefulness in detecting mutagens. The assay protocol developed by Alati et
      al. (1989) was shown to give reproducible levels of proliferating hepatocytes and
      the formation of micronuclei could be readily assessed by fluorescence
      microscopy. Epidermal growth factor and insulin were used as mitogens, yielding
      mitotic indices of 2.4 +/- 0.74% after 72 h of culture. The high number of 8.0 +/
      3.33% micronucleated hepatocytes in control cultures at that time, typically for
      in vitro stimulated hepatocytes, is probably due to disordered mitoses frequently
      leading to chromosome loss. The direct acting mutagen N-methyl-N'-nitro-N
      nitrosoguanidine and the clastogens cyclophosphamide and retrorsine, which
      require metabolic activation, induced dose dependent increases in the frequencies
      of micronucleated hepatocytes. The carcinogen 2-AAF also yielded significantly
      enhanced rates of micronuclei. The non-mutagen KCl as well as the peroxisome
      proliferator clofibrate, which is considered to be a non-genotoxic
      hepatocarcinogen, yielded consistently negative results. Problems occurred when
      chemicals exerting strong cytotoxic effects were tested in this assay. The
      mutagen and hepatocarcinogen aflatoxin B1 did not enhance the number of
      micronucleated hepatocytes. Rather a reduction of micronuclei and of mitoses was
      observed at AFB1 concentrations considered positive in other genotoxicity assays.
      Hepatocyte proliferation seems to be highly susceptible to the cytotoxic action
      of chemicals. A decrease in the proliferating activity of hepatocytes can
      obviously prevent the detection of mutagenic effects. Further studies on the in
      vitro hepatocyte micronucleus assay are necessary to clarify its role in
      mutagenicity testing.

PMID- 7504178
TI  - Isolation of cDNAs encoding the Drosophila GAGA transcription factor.
AB  - To investigate the mechanisms involved in expression of the Drosophila
      melanogaster engrailed gene, we purified GAGA protein, one of several putative
      transcriptional activator proteins that binds to the proximal region of the
      engrailed promoter. Antibodies raised against GAGA protein were used to
      demonstrate that the protein is present in all nuclei of young embryos. We
      isolated cDNA clones encoding GAGA protein in which a putative 519-codon open
      reading frame contains general sequence motifs characteristic of other
      transcription factors. These include stretches of polyglutamine, a 60-amino-acid
      region with 18 (30%) lysine or arginine residues, and a single putative zinc
      finger motif. In addition, a 120-residue N-terminal region shares significant
      sequence homology with several other known Drosophila transcription factors,
      including those encoded by Broad Complex and tramtrack. Up to 35-fold GAGA
      protein-dependent stimulation of transcription in Schneider line 2 tissue culture
      cells was observed after transfection of GAGA protein-encoding sequences. The
      GAGA gene is present in one copy in the Drosophila genome, at cytological
      location 70EF, and it encodes RNAs which vary in size between 2.4 and 4.4 kb.

PMID- 7504182
TI  - Scrape-loading: a simple method to induce chromosomal aberrations with
      restriction enzymes in CHO cells.
AB  - The restriction endonucleases AluI and EcoRI induce chromosomal aberrations in
      Chinese hamster ovary (CHO) cells when applied via scrape-loading. The
      frequencies of chromosomal aberrations induced by AluI are similar to the ones
      induced when the enzyme is applied by other methods to introduce it into cells
      (electroporation, glycerol, sorbitol). EcoRI produces lower frequencies of
      aberrations when applied via scrape-loading, as compared to the application in
      the presence of high concentrations of glycerol, which may reflect relaxed
      activities under the latter conditions.

PMID- 7504183
TI  - Studies on the genotoxicity of monocrotophos, an organophosphate insecticide, in
      the chick in vivo test system.
AB  - The mutagenic potential of an organophosphate pesticide, monocrotophos, was
      evaluated in the chick in vivo system using the chromosome aberration (CA) assay
      in bone marrow cells and the micronucleus test (MNT) in both bone marrow and
      peripheral blood erythrocytes. A significant induction of chromosome aberrations
      was observed only after 24 h of exposure with the highest dose (5 mg/kg). In
      general, monocrotophos induced a significantly higher incidence of micronuclei in
      bone marrow and peripheral blood erythrocytes over controls. From the present
      results it is concluded that monocrotophos is genotoxic in this in vivo test
      system. It is further concluded that the neonatal chick in vivo system provides
      new methodology for screening xenobiotics for mutagenicity.

PMID- 7504184
TI  - Photomutagenesis test development: I. 8-Methoxypsoralen, chlorpromazine and
      sunscreen compounds in bacterial and yeast assays.
AB  - Two in vitro genotoxicity tests have been adapted to the evaluation of
      photomutagenic activity of test compounds. The study was initiated to obtain an
      experimental basis relating to newly proposed guidelines of the EC which request
      the screening of UV-absorbing compounds, for example, those employed in sunscreen
      preparations, for their photomutagenic potential. The well established
      photomutagens 8-methoxypsoralen and chlorpromazine were used to define relevant
      test protocols. The compounds were evaluated with the Ames test and the
      Saccharomyces cerevisiae D7 test for gene conversion. The influence of various
      parameters such as UV light sources, spectral composition, UV sensitivity of the
      test systems, absorbance by test materials and different exposure conditions is
      indicated. Two exemplary screening experiments with cosmetic ingredients are
      presented. Both test systems can be employed for the evaluation of compounds for
      photomutagenic activity although the standard excision-deficient strains of S.
      typhimurium pose problems because of their high UV sensitivity. The present
      experience in this complex field suggests that rigid test protocols and a
      restrictive test battery would be inadequate.

PMID- 7504185
TI  - Photomutagenesis test development: II. 8-Methoxypsoralen, chlorpromazine and
      sunscreen compounds in chromosomal aberration assays using CHO cells.
AB  - Chromosomal changes were analysed in Chinese hamster ovary (CHO) cells treated
      with 8-methoxypsoralen (8-MOP) or chlorpromazine (CPZ) and irradiated with either
      a UVA fluorescent tube (emission spectrum ranging from 350 to 400 nm) or a xenon
      burner (continuous emission spectrum simulating ambient sunlight). In the dark
      neither 8-MOP nor CPZ was genotoxic by itself. If these compounds were used in
      combination with UV irradiation the rate of chromosome aberrations was
      significantly increased. The magnitude of the clastogenic response was dependent
      on compound concentration and UV dose. The spectral composition also played an
      important role. Care must be taken to account for spectral changes caused, e.g.,
      by passage of the light through the plastic lid of the container. The possible
      clastogenicity of two sunscreens was tested with two protocols: (1) cells
      attached to the culture dish were treated in presence of the sunscreen in the
      medium or (2) cells were irradiated through a layer of sunscreen solution as a
      filter. With this a clear UVB-absorbing effect and a decreased frequency of UVAB
      induced chromosome aberration was evident with the UVB-absorbing compound Parsol
      HS but was absent, as expected, with the UVA-absorbing compound Parsol 1789. The
      presence of the sunscreens in the irradiated cell sample did not cause a
      significant increase in UV-induced chromosome aberrations.

PMID- 7504186
TI  - Spectrum of proton-induced mutagenesis of the Escherichia coli crp gene.
AB  - Mutation of the adenosine 3',5'-cyclic monophosphate receptor protein gene (crp)
      of Escherichia coli induced by protons, ionizing radiation of charged particles,
      was analyzed to determine the specificity of the mutational spectrum. The
      majority, 44 of 49 mutations detected, were base substitutions, and three
      frameshifts and two gross structural changes were also found. Base substitutions
      included 35 transversions and nine transitions. G:C to T:A transversions were the
      dominant type of base substitution, followed by G:C to C:G and A:T to T:A
      transversions. Almost all transitions were eight G:C to A:T changes. The spectrum
      of proton mutagenesis was quite different from that of X-ray mutagenesis of the
      crp gene, in which G:C to A:T transitions dominated.

PMID- 7504187
TI  - Complementation of xeroderma pigmentosum cells by microinjection of mRNA
      fractionated under denaturing conditions: an estimation of sizes of XP-E and XP-G
      mRNA.
AB  - Excision repair deficiencies in groups A and G xeroderma pigmentosum (XP) cells
      are transiently complemented after microinjection of HeLa poly(A)+RNA, but those
      in groups D and F are not complemented (Legerski et al., 1984). We tested XP
      cells belonging to the seven complementation groups, A-G, and Cockayne's syndrome
      (CS) cells belonging to the two complementation groups, A and B, for transient
      correction by microinjection of total poly(A)+RNA from HeLa cells. Among the XP
      cells, unscheduled DNA synthesis (UDS) was increased only in XP-A cells by
      microinjection of total poly(A)+RNA. However, UDS was increased in XP-E and XP-G
      cells as well as in XP-A cells by microinjection of concentrated poly(A)+RNA
      fractionated on a 5-25% sucrose density gradient containing methylmercuric
      hydroxide. The sizes of XP-E and XP-G mRNA were estimated to be 1.5-2.7 kb and
      2.0-3.8 kb, respectively, by comparison to internal marker RNAs including 18S
      rRNA, 28S rRNA, HPRT mRNA and XPAC mRNA. RNA synthesis recovery after UV exposure
      in CS cells was not increased by microinjection of either total poly(A)+RNA or
      fractionated RNA. These results provide estimates of the sizes of XP-E and XP-G
      proteins and will facilitate molecular cloning of DNA repair genes, especially of
      XP-E and XP-G genes.

PMID- 7504188
TI  - Strand bias in mutation involving 5-methylcytosine deamination in the human hprt
      gene.
AB  - Despite being generally under-represented in the genome, CpG sequences represent
      a disproportionately high fraction of sites involved in mutational events leading
      to human genetic disease. Cytosine within CpG dinucleotides is often modified to
      5-methylcytosine. Deamination of 5-methylcytosine in situ yields a thymine, which
      being mispaired with guanine, is potentially mutagenic. Previous reports have
      indicated that most mutations recovered at these sites appear to originate on the
      non-transcribed strand as C-->T transitions. This trend may however, reflect the
      lack of detectable mutant phenotypes resulting from this transition at the
      complementary positions on the transcribed strand. To date, there has not been a
      good model system in which mutations can be recovered on both strands at the same
      CpG site. The human hprt gene has MeCpG sites contained within arginine codons
      for which mutations have been recovered on both strands. From an analysis of a
      database of hprt mutations, a statistically significant strand bias is observed
      in mutations recovered at CpG sites. We describe some models for the bias of
      mutation distribution observed at MeCpG sites in light of this and previous work
      are described.

PMID- 7504189
TI  - Effects of the umuDC, mucAB, and samAB operons on the mutational specificity of
      chemical mutagenesis in Escherichia coli: I. Frameshift mutagenesis.
AB  - The specificity of frameshift mutations induced by several classes of chemical
      mutagens was determined using a collection of mutant E. coli lacZ genes. This
      collection can detect each of five kinds of specific frameshift events by scoring
      Lac+ revertant colonies. In addition, the mutational spectra were characterized
      in backgrounds carrying plasmids that encode the umuDC, mucAB, or samAB operon. 4
      Nitroquinoline 1-oxide (4-NQO) and furylfuramide (AF-2) induced efficiently -1G, 
      2(C-G), and +1A frameshift mutations. 4-NQO and AF-2 differed in the ability for
      the induction of -1A and +1G frameshifts. +1A and -1A frameshift mutations
      induced by 4-NQO or AF-2 were enhanced by the introduction of the mucAB plasmid,
      and, to a lesser extent, the umuDC plasmid. The enhancing effect of the umuDC or
      mucAB plasmid on -1G and -2(C-G) frameshifts was weak or else not observed. 9
      Aminoacridine was a potent inducer of +1G, -1G and -1A frameshifts, whereas ICR
      191 induced all types of frameshift mutations. A mutation enhancing effect was
      observed only on ICR-191-induced +1A frameshift mutations by the introduction of
      the mucAB plasmid. Mitomycin C caused no appreciable induction of frameshift
      mutations to the tester strains without plasmid. However, all types of
      frameshifts, except -1G, were induced in the strains carrying the mucAB plasmid.
      N-methyl-N'-nitro-N-nitrosoguanidine induced all types of frameshift mutations.
      The mucAB plasmid enhanced mutagenesis in strains designed to detect the addition
      or loss of A.T base pair, indicating that the formation of +1A and -1A
      frameshifts was partly dependent on an error-prone SOS repair. Any frameshift
      mutagenesis was not affected by the samAB plasmid. In general, frameshifts in
      adenine runs were enhanced more preferentially by the mucAB and umuDC plasmids
      than frameshifts at runs of guanine were.

PMID- 7504190
TI  - Effects of the umuDC, mucAB, and samAB operons on the mutational specificity of
      chemical mutagenesis in Escherichia coli: II. Base substitution mutagenesis.
AB  - Mutational spectra induced by different classes of chemical mutagens including
      two ultraviolet-mimetic mutagens, an alkylating agent, intercalators, a
      crosslinking agent, and base analogs were characterized by means of a set of
      mutant lacZ genes in E. coli. These strains can be used to detect each of two
      types of transition and four types of transversion, simply by measuring the
      number of Lac+ revertant colonies. 4-Nitroquinoline 1-oxide induced G.C-->A.T,
      G.C-->C.G, or G.C-->T.A changes almost equally, whereas furylfuramide and
      mitomycin C induced only G.C-->A.T transitions and G.C-->T.A transversions,
      respectively. No base substitutional mutations were detected by the treatment
      with 9-aminoacridine. A weak stimulation of G.C-->A.T transitions by ICR-191 was
      observed. Both the G.C-->A.T and A.T-->G.C transitions were induced by N-methyl
      N'-nitro-N-nitrosoguanidine and N4-aminocytidine. 5-Azacytidine was a specific
      inducer of G.C-->C.G transversions. In addition, a comparative study of
      mutational specificity was performed in the strains bearing either the umuDC,
      mucAB, or the samAB operon on a multicopy plasmid. Regardless of the kind of
      mutagen, G.C-->T.A transversions were greatly potentiated by the introduction of
      plasmids in the order of pGW1700 (mucAB) > pSE117 (umuDC) > or = pYG8011 (samAB).
      Besides G.C-->T.A transversions, the introduction of pGW1700, but not pSE117 and
      pYG8011, enhanced the mutations of A.T-->C.G and A.T-->T.A transversions. The
      mucAB plasmid also enhanced the G.C-->A.T transitions and G.C-->C.G transversions
      induced by some mutagens.

PMID- 7504191
TI  - Induction of the alkylation-inducible aidB gene of Escherichia coli by
      cytoplasmic acidification and N-ethylmaleimide.
AB  - We have studied the effects of changes in intracellular pH and the influence of
      thiol reagents on the induction of the DNA damage-inducible genes of Escherichia
      coli, aidB, alkA, and alkB. Under aerobic conditions in the absence of alkylating
      agents aidB, but not alkA or alkB, was induced by an acidification of cytoplasm
      or by treatment with the sulfhydryl reagent N-ethylmaleimide. Alkaline shift and
      thiosalicyclic acid did not affect the induction of aidB and alkB. The induction
      of alkA increased under the alkaline shift but not in the case of treatment with
      reducing agents. Compared with the aidB gene, a component of the SOS system, the
      sulA (sfiA) gene, responded to changes in cytoplasmic pH and in the level of
      intracellular thiols in an opposite way. SulA induction was observed under
      alkaline shift and after treatment with thiosalicylic acid.

PMID- 7504192
TI  - Radiation-induced mitotic gene conversion frequency in yeast is modulated by the
      conditions allowing DNA double-strand break repair.
AB  - Repair of DNA double-strand breaks (DSB) involves recombinational processes which
      may lead to gene conversion (intragenic recombination). Using the diploid yeast
      mutant rad54-3 heteroallelic for his1 (his1-7/his1-1) and temperature conditional
      for DSB rejoining, radiation induced gene conversion was investigated as
      dependent on DSB repair under different postirradiation conditions. Gene
      conversion is negligible under conditions preventing DSB repair (36 degrees C).
      In contrast, gene conversion is observed when cells are incubated at the
      permissive temperature (23 degrees C) both under growth and nongrowth conditions.
      However, there is a much higher yield of convertants for cells incubated under
      growth as opposed to nongrowth conditions. These results can most plausibly be
      explained by the cell cycle regulated enhancement of the expression of genes such
      as PMS and POL3 known to be involved in gene conversion processes and/or the
      enhanced recombination in transcriptionally active genes. 'Nutrient stress'
      inducible responses and/or cell cycle specific recombination pathways leading to
      gene conversion events preferentially in S-phase cells seem to be less likely.

PMID- 7504193
TI  - G1 arrest and cell-cycle-dependent clastogenesis in UV-irradiated human
      fibroblasts.
AB  - The demonstrations of frequent allelic deletions in lung and colon cancers have
      reemphasized the importance of clastogenesis in carcinogenesis. We have
      investigated the mechanisms of induction of chromosome aberrations in ultraviolet
      irradiated diploid human fibroblasts. Cells were irradiated with UV at various
      times during a parasynchronous wave of cell proliferation and then harvested
      during the first mitosis that followed irradiation. Metaphase spreads were
      stained with Geimsa and the yields of chromosome aberrations were quantified.
      Ultraviolet irradiation induced primarily chromatid-type chromosome aberrations
      which included chromatid breaks and exchanges. Frequencies of aberrations
      displayed significant differences according to the phase of the cell cycle in
      which irradiation occurred and the time after irradiation when metaphases were
      harvested. Fibroblasts that were irradiated when in G0 and then immediately
      replated to stimulate cell division and cells that were at the S/G2 border when
      irradiated displayed the fewest numbers of aberrations. For G0-irradiated cells,
      the first entering mitosis carried a higher frequency of aberrations than those
      collected 2-4 h later. In contrast, for S/G2-irradiated cells the first into
      mitosis displayed fewer aberrations than subsequent fractions. Cells that were
      irradiated when at the G1/S border displayed the greatest numbers of aberrations
      with the frequencies of chromatic exchanges being significantly increased over
      all other times of irradiation. These studies confirm that UV is an S-phase
      dependent clastogen and point to the G1/S border as a time of maximal sensitivity
      to clastogenesis. Irradiation of G1 cells was shown to produce a fluence
      dependent reduction in the rate of entry of cells into the S-phase. There
      appeared to be a point late in G1 beyond which cells were resistant to
      irradiation and experienced less delay in S phase entry. Ataxia telangiectasia
      fibroblasts failed to delay entry to S phase following UV-irradiation in G1 and
      displayed hypersensitivity to UV-induced chromosomal aberrations. The delay in
      entry of damaged cells into the S phase may have the beneficial effect of
      providing more time for repair of potentially clastogenic DNA damage before the
      onset of DNA replication.

PMID- 7504196
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Series: Current issues in mutagenesis and carcinogenesis, No. 39.

PMID- 7504198
TI  - The adsorption of a range of dietary carcinogens by alpha-cellulose, a model
      insoluble dietary fiber.
AB  - One of the ways dietary fibers may protect against colorectal cancer is by
      adsorbing carcinogens and carrying them out of the digestive tract, thus
      lessening interaction of the carcinogens with the colonic tissue. We investigated
      this mechanism of action by testing in vitro the abilities of a range of
      carcinogens, including known animal colon carcinogens, to adsorb to alpha
      cellulose, which we have used as a model insoluble dietary fiber. The carcinogens
      were N-nitroso-N-methylurea (NMU), benzo[a]pyrene (B[a]P) and a number of
      heterocyclic aromatic amines which have been found in heated foods. It was found
      that the ability of a carcinogen to adsorb to alpha-cellulose is strongly related
      to the hydrophobicity of the carcinogen measured as the calculated logarithm of
      the partition coefficient between 1-octanol and water (C log P). The hydrophilic
      carcinogen, NMU, (C log P = -0.204), adsorbed only poorly, whereas the very
      hydrophobic carcinogen, B[a]P, (C log P = 6.124), adsorbed strongly. Carcinogens
      with intermediate hydrophobicities showed intermediate abilities to adsorb.

PMID- 7504194
TI  - Loss of S-phase-dependent radioresistance in irs-1 cells exposed to X-rays.
AB  - We measured radiosensitivity throughout the cell cycle in parental V79 cells and
      a radiation-sensitive mutant isolated from them, irs-1 (Jones et al. (1987)
      Mutation Res., 183, 279-286). We observed, as expected, large fluctuations in
      radiosensitivity throughout the cell cycle in parental V79 cells exposed to 5 or
      9 Gy X-rays; cells irradiated at the G1/S border were generally radiosensitive
      whereas cells irradiated in mid- or late-S phase were radioresistant. In sharp
      contrast to this result, irs-1 cells showed a relatively flat response of
      radiosensitivity throughout the cell cycle mainly due to a lack of
      radioresistance during S. In general, irs-1 cells were maximally radiosensitive
      in phases of the cell cycle where V79 cells were radioresistant, and equally
      radiosensitive to V79 cells when compared at mitosis, the most radiosensitive
      phase of the V79 cell cycle. The results suggest that the subset of radiation
      induced lesions whose repair is compromised by the irs-1 mutation is similar to
      the subset of lesions whose repair or expression causes the fluctuations in
      radiosensitivity throughout the cell cycle in repair-proficient cells. These
      observations add another unique phenotypic characteristic to the irs-1 mutation.

PMID- 7504195
TI  - Restoration of the DNA damage resistance of Deinococcus radiodurans DNA
      polymerase mutants by Escherichia coli DNA polymerase I and Klenow fragment.
AB  - Deinococcus radiodurans and other species of this genus share extreme resistance
      to ionizing radiation and many other agents that damage DNA. D. radiodurans
      mutant strains defective in a deinococcal DNA polymerase that is homologous with
      E. coli DNA polymerase I are highly sensitive to DNA damage. In the current work
      we have inquired whether E. coli DNA Pol I can substitute for D. radiodurans Pol
      in partially or fully restoring to pol- D. radiodurans mutants the extreme DNA
      damage-resistance typical of this organism. The E. coli polA gene or a 5'
      truncated polA gene that encodes the Klenow fragment were introduced and
      expressed in two different D. radiodurans pol- mutants: Strain 303, which is a
      chemically mutagenized derivative, and strain 6R1A, which is isogenic with wild
      type D. radiodurans except for an insertional mutation within the pol gene.
      Expression of E. coli polA in both of these mutants fully restored wild-type
      resistance to ionizing- and UV254-radiation and mitomycin-C exposure. Expression
      of the Klenow fragment-encoding gene restored wild-type resistance to D.
      radiodurans strain 303, but only partial resistance to strain 6R1A. The
      observation that E. coli DNA Pol I is as effective as D. radiodurans Pol in
      restoring damage resistance, indicates that D. radiodurans DNA Pol per se does
      not have special properties that are essential or prerequisite for expression of
      the extreme resistance of D. radiodurans.

PMID- 7504197
TI  - Evaluation of exposure reducing measures on parameters of genetic risk in a
      population occupationally exposed to coal fly ash.
AB  - In a previous study we found increased SCE frequencies in peripheral blood
      lymphocytes (PBLs) of workers occupationally exposed in a coal fly ash processing
      industry, as compared to a non-exposed control population. Shortly after this
      study, measures were taken in this plant to reduce fly ash levels. The objective
      of the present study, conducted 2 years later in the same plants, was to evaluate
      the effect of these measures with respect to genotoxic risk. A group of 18 male
      workers of the coal fly ash processing industry agreed to participate in the
      study. The control population consisted of 18 male workers from a flour
      processing industry, who were matched for age and smoking behavior. In contrast
      to our previous study, no increased SCE frequencies were found in PBLs of workers
      potentially exposed to coal fly ash when compared to the control group (mean
      SCEs: 6.4 +/- 1.2 and 7.0 +/- 0.9, respectively). In addition, no differences
      were observed between the exposed and control groups for frequencies of gene
      mutations at the hypoxanthine guanine phosphoribosyltransferase (hprt) locus in
      PBLs, for micronucleus frequencies using the cytokinesis block method, or for
      urinary mutagen excretion measured with Salmonella typhimurium tester strains
      TA98 and TA97 with and without metabolic activation. In smokers, however, SCE
      frequencies in PBLs were significantly increased in comparison to non-smokers
      (7.1 +/- 1.1 vs. 6.1 +/- 0.5; P < 0.005), as was 24-h urinary mutagen excretion
      measured with strain TA98 with S9 mix (2373 +/- 1870 vs. 156 +/- 211; P < 0.001)
      and with TA98 with S9 mix and beta-glucuronidase/arylsulfatase (2361 +/- 1958 vs.
      538 +/- 396; P < 0.005). In addition, hprt variant frequencies in PBLs were
      higher in smokers than in non-smokers (15.0 +/- 23.5 x 10(-6)6 vs. 2.6 +/- 2.8 x
      10(-6); P < 0.05). No differences were observed for micronucleus induction
      between smokers and non-smokers. It is concluded that the protective measures
      taken in the coal fly ash processing plant appear to have been sufficient, since
      an effect of exposure to coal fly ash on parameters of genetic risk was not found
      any longer.

PMID- 7504199
TI  - Micronucleus frequency in cultured lymphocytes of an urban population.
AB  - The frequencies of micronuclei in cultured cytokinesis-blocked lymphocytes of an
      urban industrial population of 188 persons were determined. For the mean and SD,
      16.0 +/- 7.3 per 1000 CB cells were obtained. A slight but definite age
      dependence--appr. 0.2/1000 increase per year on average--was indicated by
      thorough statistical analysis.

PMID- 7504200
TI  - Mutagenic activity of three synthetic isomers of the food carcinogen 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ) in the Ames test.
AB  - The mutagenic activities of three isomers of IQ, with the pyridine N-atom at
      different positions, were measured in the Ames test with Salmonella typhimurium
      TA98 and enzymatic activation (S9). All test compounds showed lower activities
      than IQ. Interestingly, the amount of protein in the S9 mix does not seem to
      influence the mutagenic activity of the '8-IQ' isomer.

PMID- 7504201
TI  - Urinary mutagenic activity after different immunosuppressive protocols in renal
      transplant patients.
AB  - Cyclosporin (CsA) and azathioprine (AZA) are useful immunosuppressive drugs in
      the management of kidney and liver transplant recipients. We investigated urinary
      mutagenicity in three groups of kidney transplant recipients after different
      immunosuppressive protocols. Urinary mutagenicity was detected in a base-pair
      strain, E. coli WP2uvrA, in a liquid incubation assay. No mutagenic activity was
      detected in the urines of patients treated with CsA (4.5 mg/kg); 85% of the
      urines in the second group treated with AZA (1.26 mg/kg) showed high mutagenic
      activity, whereas mutagenic activity was found in 40% of the urines of subjects
      treated with CsA and AZA (3.89 mg/kg + 1.15 mg/kg). These data suggest that
      immunosuppressive therapy with AZA carriers a high risk of urinary mutagenicity,
      while immunosuppressive combined treatment with CsA and AZA significantly reduces
      this risk.

PMID- 7504202
TI  - Dominant-lethal mutations and micronucleus induction in male BALB/c, BDF1 and H
      mice by tobacco smoke.
AB  - The mutagenicity of whole tobacco smoke (TS) was examined in male BALB/c, BDF1
      and H mice using the dominant lethal and micronucleus tests in bone marrow
      polychromatic erythrocytes. Male mice (about 80 days old) from the three strains
      were treated with TS on 5 days/week for 8 weeks. The animals were divided into
      three groups for every strain: control and two experimental groups. Two doses-
      low (1h treatment/day) and high (2 h treatment/day)--were used. In the first case
      8 exposures of 7.5 min each with 1-min intervals were given and to realize the
      high dose this was repeated 4 h later. It was found that TS induces significant
      dominant-lethal mutations in both experimental groups of BALB/c, BDF1 and H mice
      (p < 0.001), but some strain differences existed. The data obtained suggest that
      in BALB/c and BDF1 mice TS induces dominant-lethal mutations mainly in
      spermatocytes, spermatogonia and gonial stem cells, while in H mice only
      spermatids and spermatocytes are affected. The bone marrow from each strain and
      each dose group was investigated for the presence of micronucleated polychromatic
      erythrocytes (PCE) at 5, 19, 38, 54, and 63 days after beginning of the treatment
      with TS, using the same exposure regimen. Exposure of male mice to TS caused an
      up to 2-3-fold increase in the number of PCE in the bone marrow of BALB/c and
      BDF1 mice in both dose groups. In H mice this effect is observed only on days 19
      and 38 of sampling. No cumulative or dose-dependent effects were detected.
      Increased formation of micronuclei within PCE of femoral bone marrow after
      passive smoking was regarded as being due to the effect of TS.

PMID- 7504203
TI  - Two years' air mutagenesis monitoring in a northwestern rural area of Italy with
      an industrial plant.
AB  - The mutagenicity of organic extracts from inhalable airborne particles, collected
      in a northwestern rural area of Italy in which an industrial plant producing
      chemical intermediates is present, was assessed during the years 1989 and 1990.
      The Ames plate test with Salmonella strains TA98 and TA100 with and without
      metabolic activation was used. Eight sites in the first and three sites in the
      second year were monitored once and twice a month respectively. Results show that
      the mutagenicity of air particulate matter reaches maximum values in the cold
      months and is not dependent on plant activities. In addition, a correlation
      analysis between mutagenicity data and number of vehicles seems to indicate
      traffic emissions as the main source of mutagens.

PMID- 7504204
TI  - Peculiarities of the clastogenic properties of chrysotile-asbestos fibers and
      zeolite particles.
AB  - It has been established that chrysotile-asbestos fibers and zeolite particles
      induce chromosome aberrations in human lymphocytes from whole blood cultures,
      peritoneal fluid cells and bone marrow cells of mice. It is shown that the level
      of cytogenetic response from the intraperitoneal administration of chrysotile
      asbestos fibers and zeolite particles depends on the time of their exposure.
      Further, it is shown that SOD eliminates the cytogenetic effect of chrysotile
      asbestos fibers, while catalase inhibits that of zeolite particles.
      Recommendations concerning testing for the mutagenic properties of mineral fibers
      and particles are given, and possible mechanisms of their damaging effects are
      discussed.

PMID- 7504206
TI  - Cytogenetic monitoring of a village population potentially exposed to a low level
      of environmental pollutants. Phase 1:SCE analysis.
AB  - By analogy to the techniques applied for monitoring biological effects of
      exposure to genotoxic agents in occupational populations, we have carried out
      cytogenetic monitoring in a group of inhabitants of a village (Mellery, Belgium)
      suspected to have been exposed to a variety of toxic environmental pollutants.
      These pollutants probably originated from a neighboring chemical wastes site. A
      group of 51 environmentally exposed and 52 reference persons (including children)
      were examined for the frequency of sister-chromatid exchanges (SCE) in their
      peripheral blood lymphocytes. The technique was further refined by using a high
      frequency cells (HFC) analysis. Analysis of the reference subgroups showed a
      significant difference between non-smoking adults and children. The influence of
      tobacco was clear, too. In the exposed group, no significant differences could be
      demonstrated between either the smokers or the non-smokers or the children.
      Furthermore, not only were the mean frequencies of SCE higher than in the
      respective reference subgroups but comparison between the two groups also showed
      a higher number of individuals presenting a HFC level above the background in the
      exposed group. Surprisingly, the difference was more pronounced for the children.
      A follow-up of the same exposed population carried out 18 months later and after
      remediation of the atmospheric chemical release, the previously observed
      tendencies in the exposure parameter remained unmodified.

PMID- 7504205
TI  - Effect of vitamin E dietary intake on in vitro activation of aflatoxin B1.
AB  - The molecular mechanism of action of vitamin E on mammalian cells remains to be
      elucidated. In this study, vitamin E dietary intake was assessed for its effects
      on the initiation phase of carcinogenesis. We have conducted a dose-effect
      relationship between vitamin E dietary intake and aflatoxin B1 (AFB1)
      genotoxicity measured in vitro. Thus AFB1 induced mutagenesis in Salmonella
      typhimurium TA98 was investigated and compared to effect of vitamin E dietary
      intake on hepatic microsomal P-450 content and specific activities involved in
      AFB1 metabolism. Rats were fed ad libitum a diet containing 0, 0.05, 0.5 or 5 IU
      of alpha-tocopherol for 8 weeks. Modulation of vitamin E level in
      postmitochondrial and microsomal fractions resulted in nutritional effects.
      Cytochrome P-450 content was not modified by the level of vitamin E in the diet.
      The microsomal P-450 activities, P-450 IIB1 and IIIA, were decreased in the
      deficient group to -35% and -16%, respectively, as compared with control diet
      (0.05 IU). Diet supplemented with 0.5 IU of vitamin E increased P-450 IIB and
      IIIA activities (+28% and +37%, respectively) whereas a diet highly supplemented
      in vitamin E (5 IU) reduced these specific P-450 activities. Lipid peroxidation,
      estimated by the formation of thiobarbituric acid reactive products, increased in
      the dietary vitamin E free diet (+20%) and strongly decreased in the supplemented
      group (-99%). This study establishes that in vivo, dietary vitamin E protects
      directly membrane against damage induced by lipid peroxidation and indirectly
      hepatic microsomal monooxygenase activities. However, vitamin E accumulation
      seems to alter membrane structure and function. The nutritional effect of vitamin
      E on hepatic microsomal cytochrome P-450 activities modified the AFB1
      genotoxicity measured in vitro.

PMID- 7504207
TI  - Mutagenicity of four homo-aza-steroidal esters of m-N,N-bis(2
      chloroethyl)aminocinnamic acid in the Ames test.
AB  - Four new chemicals, the homo-aza-steroidal esters of m-N,N-bis(2
      chloroethyl)aminocinnamic acid, originaly synthesized to be used as
      antineoplastic agents, were tested for their mutagenic activity in the Ames test.
      3 beta-Hydroxy-13 alpha-amino-13,17-seco-5-androsten-17-oic-13,17- lactam ester
      (ACALE3) and 3 alpha-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic
      13,17-lactam ester of m-N,N-bis(2-chloroethyl)aminocinnamic acid (ACALE4) were
      found to induce base-pair substitutions, causing dose-dependent increases in his+
      revertants in strains TA100 and TA1535, while no dose-dependent relations were
      established when 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17
      oic-13,17-lactam ester (ACALE1) and 17 beta-hydroxy-3-aza-A-homo-4 alpha
      androsten-4-one ester of m-N,N-bis(2-chloroethyl)aminocinnamic acid (ACALE2) were
      tested. The presence of metabolic activation enzymes in the test system had no
      effect in his+ revertants in strains TA100 and TA1535. The chemicals tested
      although having the same alkylating moiety and a similar chemical structure
      exhibited different mutagenic activities.

PMID- 7504208
TI  - Risk factors for hepatocellular carcinoma in patients with chronic liver
      diseases.

PMID- 7504209
TI  - CD44--a new prognostic marker for neuroblastoma.

PMID- 7504210
TI  - The L-arginine-nitric oxide pathway.

PMID- 7504211
TI  - Renal tubular antiproteinase (alpha-1-antitrypsin and alpha-1-antichymotrypsin)
      response in tubulo-interstitial damage.
AB  - We studied the role of proteinase inhibitors (Pls) alpha 1-antitrypsin and alpha
      1-antichymotrypsin in relation to lysozyme (LZM), and membrane attack complex
      (C5b-9) in renal tubular damage by immunohistochemical techniques. Fifty-five
      cases, including 45 patients with glomerular diseases, and 10 controls were
      studied. The patients were divided into two groups; one with tubulo-interstitial
      lesions (TILs; 30 cases), and the other without (15 cases). Significant
      antiproteinase response was observed in the proximal tubules in both disease
      groups, indicating that they were subjected to proteolytic attack. This response
      correlated with proteinuria and occurred in tubules which showed protein
      reabsorption as demonstrated by the presence of LZM staining in consecutive
      serial sections. Increased deposition of membrane attack complex (C5b-9) was
      observed in the disease group with TILs, indicating direct damage to cell
      membranes. C5b-9 may also generate oxygen species, potent inhibitors of Pls,
      which allow the proteases to cause tubular damage.

PMID- 7504212
TI  - Serum and urinary alpha-1 acid glycoprotein in chronic renal failure.
AB  - The concentration and concanavalin A (ConA)-dependent microheterogeneity of serum
      and urinary alpha 1-acid glycoprotein (AGP) were studied in patients with various
      degrees of renal impairment and compared with healthy control values. Serum
      concentrations of AGP were significantly higher in hemodialyzed and uremic
      patients than in the control subjects (1.54 +/- 0.42 g/l, p < 0.05, and 1.20 +/-
      0.40 g/l, p < 0.05, respectively, versus 0.83 +/- 0.17 g/l). There was a similar
      increase in serum alpha 1-protease inhibitor and haptoglobin concentrations in
      the uremic patients (r = 0.87 and r = 0.70; p < 0.001). Urinary concentrations of
      AGP were also significantly higher in the hemodialyzed and uremic patients than
      in the control subjects, despite wide variability in the patients (20 +/- 14
      mg/24 h, p < 0.05, and 126 +/- 160 mg/24 h, p < 0.05, respectively, versus 3 +/-
      1 mg/24 h). AGP clearance was significantly higher in the uremic patients than in
      the hemodialyzed patients (p < 0.01) and the control subjects (p < 0.01). The
      proportions of strongly ConA-reactive AGP fractions were higher in the serum of
      the hemodialyzed (18.6 +/- 5.2%; p < 0.05) and uremic patients (18.1 +/- 5.3%; p
      < 0.05) than in the control subjects (14.5 +/- 2.5%). There was a similar
      difference in the urine samples (26.7 +/- 8.2%, p < 0.01; 20.1 +/- 6.2%, p <
      0.01, respectively, versus 10.3 +/- 4.8%), with also a significant difference
      between the hemodialyzed and uremic patients (p < 0.05).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7504214
TI  - Induction of fetal hemoglobin with erythropoietin.

PMID- 7504215
TI  - Comparison of the effects of (+/-) CP 96,345 and L-668,169 on neurokinin receptor
      mediated responses in rat and guinea-pig isolated tissues.
AB  - The effects of (+/-) CP 96,345 and L-668,169 on NK1-, NK2- and NK3-receptor
      mediated contractile responses were compared in guinea-pig and rat isolated
      smooth muscle tissues. Both (+/-) CP 96,345 and L-668,169 inhibited NK1-mediated
      responses in guinea-pig ileum (pA2 = 9.3 and 6.4 respectively) but not in rat
      bladder (pKB = < 6 and < 5.5 respectively) consistent with species differences in
      NK1-receptor pharmacology. Both compounds showed some selectivity in inhibiting
      NK1-receptor evoked responses in guinea-pig ileum compared to their inhibitory
      effects on NK2-receptor mediated responses in guinea-pig bladder and rat ileum
      and NK3-mediated responses in guinea-pig ileum and rat portal vein.

PMID- 7504216
TI  - Activation of metabotropic glutamate receptors induces an inward current in rat
      dopamine mesencephalic neurons.
AB  - To investigate the electrophysiological effects of the stimulation of the
      metabotropic excitatory amino acid receptors, we applied trans-1-amino
      cyclopentane-1,3-dicarboxylate, an agonist of this type of receptors, on presumed
      rat dopamine cells intracellularly recorded in vitro. Trans-1-amino-cyclopentane
      1,3-dicarboxylate (3-30 microM, t-ACPD) caused a sustained increase of the
      spontaneous firing rate and a depolarization. When the membrane potential was
      held at about the resting level (-50, -60 mV), by the single-electrode voltage
      clamp technique, t-ACPD induced an inward current. In 57% of the tested cells the
      inward current was associated with a decrease of the apparent input conductance.
      In the remaining cells no obvious changes in membrane conductance were observed.
      The active form of t-ACPD, (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylate [3-50
      microM, (1S,3R)-ACPD] also produced a reversible inward current on the
      dopaminergic cells and this was antagonized by (S)-4-carboxy-3
      hydroxyphenylglycine (300 microM), a selective antagonist of the (1S,3R)-ACPD
      induced depolarization on central neurons. The (1S,3R)-ACPD-induced inward
      current was not antagonized by L-2-amino-3-phosphonopropionic acid (100 microM),
      an antagonist of the t-ACPD-induced activation of inositide synthesis. 6-cyano-7
      nitroquinoxaline-2,3-dione (10 microM), an alfa-amino-3-hydroxy-5- methyl
      isoxazole propionic acid/kainate antagonist, DL-amino-5-phosphonopentanoic acid
      (30 microM), an N-methyl-D-aspartate antagonist, and scopolamine (10 microM), a
      muscarinic antagonist, did not significantly affect the actions of t-ACPD. A
      block of synaptic transmission obtained by applying tetrodotoxin failed to
      prevent the action of t-ACPD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504217
TI  - Transient ipsilateral innervation of the cerebellum by developing olivocerebellar
      neurons. A retrograde double-labelling study with fast blue and diamidino yellow.
AB  - In neonatal rats the injection of Fast Blue and Diamidino Yellow retrograde
      fluorescent tracers, each into separate cerebellar hemispheres, reveals the
      presence of double-labelled neurons positioned bilaterally in the inferior
      olivary complex during the early postnatal period (postnatal day 0 to postnatal
      day 5). This suggests that those neurons whose axons are able to take up both
      tracers project to both hemicerebellar during this period of postnatal
      development. Double-labelled neurons were observed in one- and five-day-old
      injected postnatal rats, but were absent in older animals (10 and 30 days old).
      The presence of these neurons coincides with a transient period of poly
      innervation of Purkinje cells by climbing fibres. They may thus be participating
      in transitory interactions preceding the formation of definitive climbing fibre
      synaptic arrangements in the cerebellar cortex. The technique employed is unable
      to clearly define the pathway of this transient olivocerebellar projection into
      the ipsilateral cerebellum; however, in direct evidence--like the topographic
      distribution of double-labelled neurons relative to tracer injection sites, and
      the small number of single-labelled neurons within the ipsilateral olivary
      complex, together with previous data on the axonogenesis of olivary neurons
      [Bourrat and Sotelo (1988) Devl Brain Res. 39, 19-37]--suggests that these fibres
      reach the cerebellum through the contralateral inferior cerebellar peduncle and
      give rise to collaterals, some of which subsequently decussate again within the
      cerebellum. These fibres probably represent transient collaterals of the normally
      contralateral olivocerebellar fibres that cross the cerebellar midline and reach
      mirror-image loci within the ipsilateral hemicerebellum.

PMID- 7504213
TI  - Induction of fetal hemoglobin by recombinant human erythropoietin in patients
      with end-stage renal disease.

PMID- 7504218
TI  - Immunohistochemical localization of 3',5'-cyclic guanosine monophosphate in the
      canine proximal colon: responses to nitric oxide and electrical stimulation of
      enteric inhibitory neurons.
AB  - There is growing evidence that nitric oxide serves as a neurotransmitter released
      from enteric inhibitory nerves in the gastrointestinal tract. The distribution of
      nitric oxide synthase suggests that nitric oxide may also be a neurotransmitter
      within enteric ganglia. Since many actions of nitric oxide are mediated by
      stimulation of soluble guanylate cyclase and a subsequent increase in 3',5'
      cyclic guanosine monophosphate (cGMP) concentration, targets for nitric oxide in
      the canine proximal colon were investigated by immunohistochemical localization
      of cGMP. In the presence of phosphodiesterase inhibitors (M&B 22948, 100 microM
      and 3-isobutyl-1-methyl-xanthine, 1 mM), exogenous nitric oxide and electrical
      field stimulation caused an accumulation of cGMP-like immunoreactivity in several
      cell-types including colonic smooth muscle cells. cGMP-like immunoreactivity was
      also observed in a subpopulation of neurons in both myenteric and submucosal
      ganglia. Sequential labeling with the NADPH diaphorase technique showed that 94%
      of neurons that responded to exogenous nitric oxide with an increase in cGMP-like
      immunoreactivity were NADPH diaphorase negative. None of the myenteric neurons
      that responded to electrical field stimulation with an increase in cGMP-like
      immunoreactivity were NADPH diaphorase positive, and only one submucosal neuron
      with cGMP-like immunoreactivity was also NADPH diaphorase positive. The
      electrical field-stimulated increase in cGMP-like immunoreactivity was blocked by
      nitroarginine (100 microM). An increase in cGMP-like immunoreactivity also
      occurred in interstitial cells located at the submucosal surface of the circular
      muscle layer. These cells are interposed between nerve varicosities and smooth
      muscle cells and may partially mediate neuromuscular transmission. Sodium
      nitroprusside and nitric oxide also caused an accumulation of cGMP-like
      immunoreactivity in smooth muscle cells of intramural arterioles and venules. The
      results of this study further support the role of nitric oxide as a
      neurotransmitter in colonic muscles, and provide support for the hypothesis that
      interstitial cells are functionally innervated by enteric inhibitory neurons. The
      data also suggest that nitric oxide may serve as a neurotransmitter in enteric
      ganglia.

PMID- 7504219
TI  - [Feasibility of a cyclophosphamide methotrexate and 5-fluorouracil regime
      intravenously administered with and without granulocyte-colony stimulating factor
      in surgically treated breast carcinoma].
AB  - The aim of this study was to evaluate the feasibility of CMF 1.8-28 regimen, with
      all three drugs administered intravenously (IV), and to compare the hematologic
      toxicity of this regimen with or without G-CSF. Patients aged 18 to 65 years with
      histologically proven breast cancer treated by surgery and without distant
      metastases were eligible for the study. All patients had to have normal white
      blood cells (WBC) count (WBC > or = 3000/mm3 and/or neutrophils > or = 2000), and
      platelets (Plt) counts (> or = 100,000/mm3), and adequate renal and hepatic
      function. The toxicity was recorded according to World Health Organization Scale.
      CMF 1.8 regimen was: cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5
      fluorouracil 600 mg/m2. The drugs were given IV on day 1 and 8, and cycles
      repeated every 28 days. G-CSF (5 micrograms/kg/day) was administered
      subcutaneously from day 9 to 20, starting from the second cycle of chemotherapy.
      A complete blood count with white-cell differential and platelet count was
      obtained twice a week. For each patient bone marrow toxicity variables recorded
      during the first cycle (without G-CSF) were compared with values during the
      second cycle (with G-CSF). One of 10 entered patients, 1 was not evaluated due to
      missing data on hematologic toxicity. All patients received chemotherapy with or
      without G-CSF at the scheduled 28th day. Treatment with G-CSF after CMF 1.8
      regimen resulted in a significantly WBC's earlier nadir (average day of nadir 14
      vs 17; p = 0.0005), while there was no difference in the average values of WBC at
      the nadir. Moreover, the average value of platelets recorded at the nadir was
      significantly lower with the use of G-CSF (average No. of platelets/mm3; 185,111
      vs 116,000; p = 0.001). Complete hematologic recovery without and with G-CSF was
      reached on day 25 and 20 respectively (p = 0.001). CMF 1.8 with IV
      cyclophosphamide is a feasible regimen with and without G-CSF and can be used in
      adjuvant setting instead of "classic" CMF in order to improve the low compliance
      observed when cyclophosphamide is given by mouth. As reported by others, we
      observed that after standard chemotherapy G-CSF anticipated the nadir of WBC and
      hastened hematologic recovery (WBC > 3000 and Plt > or = 100,000).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7504220
TI  - Expression of an outwardly rectifying K+ channel in rat microglia cultivated on
      teflon.
AB  - Membrane currents of cultured human monocytes and rat microglia were recorded
      with the whole-cell patch clamp technique. Freshly isolated monocytes or resting
      (proliferating) microglia express only inwardly rectifying K+ channels. However,
      incubation in teflon bags leads to the expression of additional, outwardly
      rectifying K+ channels. The outward K+ conductance of microglial cells was
      inhibited by intracellular Cs+ and extracellular 4-aminopyridine or
      tetraethylammonium. Functional similarities with the microglial outwardly
      rectifying K+ channel were found in the Kn-channel of lymphocytes which has
      recently been cloned (RGK5). The polymerase chain reaction (PCR) was used to
      demonstrate the presence of RGK5-like mRNA in microglia.

PMID- 7504221
TI  - Voltage dependencies of the effects of chlorpromazine on the nicotinic receptor
      channel from mouse muscle cell line So18.
AB  - The effects of chlorpromazine (CPZ) on nicotinic acetylcholine receptor (nAChR)
      were re-investigated by patch-clamp recordings on a mouse muscle cell line: (1)
      CPZ decreased the channel-opening frequency and, thus, acted as a closed-channel
      blocker. This effect was independent of the membrane potential and was consistent
      with an enhanced desensitization of the nAChR. (2) In addition, CPZ decreased the
      mean channel open time of the nAChR in a concentration- and voltage-dependent
      manner and, thus, behaved as an open-channel blocker. The latter effect supports
      the notion that CPZ binds to a site within the nAChR ionic channel.

PMID- 7504222
TI  - Nitric oxide synthase inhibitors block long-term potentiation induced by weak but
      not strong tetanic stimulation at physiological brain temperatures in rat
      hippocampal slices.
AB  - Nitric oxide synthase (NOS) inhibitors have been shown to block long-term
      synaptic enhancements in the mammalian hippocampus. This effect has been somewhat
      controversial, however, showing sensitivity to both temperature and stimulus
      strength. We have demonstrated a differential effect of the NOS inhibitor L-NG
      nitroarginine (NOArg) on long-term potentiation (LTP) induced by weak and strong
      tetanic stimulation in slices of rat hippocampus. NOArg prevented LTP induction
      by a weak tetanus that produced stable potentiation in control slices, while the
      NOS inhibitor was without effect when strong tetani were used. These results
      suggest that nitric oxide (NO) produced as a result of tetanic stimulation plays
      a role in adjusting the threshold of LTP induction, but is not necessary for
      establishing synaptic enhancement under conditions of strong synaptic activation.

PMID- 7504224
TI  - Parallel alterations in Met-enkephalin and substance P levels in medial globus
      pallidus in Parkinson's disease patients.
AB  - Met-enkephalin (Met-enk) and substance P (SP) were measured by a combined high
      performance liquid chromatography/radioimmunoanalysis method in medial (GPM) and
      lateral globus pallidus (GPL) from controls and from Parkinson's disease (PD)
      patients. All patients showed a similar marked (> 90%) reduction in dopamine (DA)
      levels in putamen compared with controls. However, based on DA levels in the
      caudate nucleus, two subgroups of PD patients were differentiated. In patients
      with > 80% decrease in caudate nucleus DA content, there was a three-fold
      increase in both Met-enk and SP levels in GPM. In contrast, in patients showing
      an approximately 50% reduction in DA content in caudate, levels of both peptides
      were markedly reduced (approximately 80%). Met-enk and SP levels in GPL were
      unchanged in PD. These results suggest that neurons containing Met-enk and SP
      projecting to GPM adapt according to the extent of degeneration in the substantia
      nigra in PD.

PMID- 7504223
TI  - Glutamate, GABA, calbindin-D28k and parvalbumin immunoreactivity in the pulvinar
      lateralis posterior complex of the cat: relation to the projection to the Clare
      Bishop area.
AB  - Neurons of the pulvinar-lateralis posterior complex (Pul-LP) containing glutamate
      (Glu) and GABA, as presumed neurotransmitters, and calbindin- D28k (calbindin)
      and parvalbumin (PV), as Ca-binding proteins, were identified in the cat by using
      immunohistochemical methods. In vibratome sections, neurons immunoreactive (IR)
      to each of the four antibodies were observed throughout the Pul-LP. In semithin
      sections, GABA-IR neurons were also PV-IR but not calbindin-IR and some of them
      also co-localized Glu. The Glu-IR neurons which were negative for GABA co
      localized calbindin but not PV. The neurons of the Pul-LP projecting to the Clare
      Bishop area (CB) in the suprasylvian gyrus were identified with a retrogradely
      transported tracer and the sections were then immunostained for Glu, GABA,
      calbindin and PV. Only Glu- and calbindin-IR neurons were retrogradely labeled.
      These results show that, if calbindin and PV have a Ca-binding role, the
      presumably excitatory Glu-IR neurons projecting to the CB are use calbindin
      whereas the presumably inhibitory GABA-IR neurons are intrinsic and use PV. This
      relationship implies that these proteins probably have other roles specifically
      related to the kind of agonist to be released at the neuron.

PMID- 7504225
TI  - Spinothalamocortical inputs nonpreferentially innervate the superficial and deep
      cortical layers of SI.
AB  - Using a combined anterograde and retrograde tracing technique, we examined the
      distribution pattern of the thalamocortical cells which projected to superficial
      layers of the hand region of the primary somatosensory cortex (hSI), and
      quantitatively analyzed the retrogradely labeled cells which putatively contacted
      terminals of the spinothalamic tract (STT) in the squirrel monkey and the
      macaque. Less than 25% of the superficial hSI projecting cells were putatively
      contacted by terminals of cervical enlargement spinothalamic neurons. These cells
      were primarily located in ventroposterior lateral, ventroposterior inferior and
      centrolateral nuclei. Although the number of superficial hSI projecting cells
      numbered less than 20% of the total hSI projecting cells, their patterns of
      location and their proportion of overlap with STT terminals within each thalamic
      nucleus were similar. It is suggested that the spinothalamic nociceptive
      information input to to the cortex equally accesses both superficial and deep SI.

PMID- 7504227
TI  - The current status of childhood low-level lead toxicity.
AB  - Lead's toxicity has been recognized since antiquity, and certain themes recur
      during the history of its understanding. Warnings have been frequently
      pronounced, and frequently followed by statements that these warnings were
      exaggerated. Childhood lead poisoning was first discovered in Brisbane, Australia
      in 1894. The cause, lead on the rails of the porches, was demonstrated by J.L.
      Gibson, and promptly derided by the business and medical communities. The first
      lead paint prevention act was passed in Australia in 1920. In the United States,
      it was believed that if a lead-poisoned child did not die, they recovered with no
      residua. This was disproved by R.K. Byers in 1943, and the modern era of
      childhood lead poisoning was begun. In the 1960's, the defined toxic level of
      lead in the blood was 60 micrograms/dl. In some areas, as many as 20% of children
      had blood lead levels above 40 micrograms/dl. Questions about silent toxicity at
      these doses were raised. Studies of lower lead exposure began to be published in
      the early 1970's. Some reported an effect, others did not. Many of these early
      studies were of small sample size, used crude measures of outcome, relied on a
      short term markers of exposure, and had limited control of covariates. In the
      latter part of the 1970's, studies of better quality reported positive
      relationships between lead and IQ. We used tooth lead levels to classify
      asymptomatic 1st and 2nd grade children and, controlling for socioeconomic
      status, mother's IQ and other potential confounders, demonstrated that high lead
      in the teeth was associated with decreased IQ, impaired attention, and impaired
      speech performance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504226
TI  - Epidemiologic approaches to assessing the developmental toxicity of lead.
AB  - A variety of designs have been employed in epidemiologic studies of the
      developmental morbidity associated with low-level lead exposure. Historically,
      cross-sectional and retrospective cohort designs have been used most frequently.
      Despite improvements in their methodological rigor, however, certain design
      features constrain the inferences such studies can support. These limitations
      stem from the substantial risk that children's exposure status may be
      misclassified due to reliance on indices with short averaging times, and an
      inability to identify either age-related changes in vulnerability or time
      dependent aspects of the expression of toxicity (e.g., reversibility). In
      response to these limitations, several studies were initiated involving repeated
      measurements of children's lead exposure and development over periods as long as
      a decade. Although these prospective studies are characterized by an unusual
      degree of coordination among the investigators, there are differences among them
      as well, most notably in terms of sample characteristics and patterns of
      exposure. As a result, the studies should be viewed as complementary rather than
      simply as replicates of one another. Moreover, like all epidemiologic approaches
      the prospective design has its own limitations. These include the need to
      maintain follow-up over a long period of time, as well as the attendant risk of
      bias in sample attrition, and the need to distinguish developmental effects of
      lead from psychometric artifacts. The Boston prospective study is used to
      illustrate both the strengths and weaknesses of the prospective design.

PMID- 7504228
TI  - Differential neurotoxicological effects of lead on voltage-dependent and receptor
      operated ion channels.
AB  - Mouse neuroblastoma cells of the clone N1E-115 express a variety of ion channels
      and receptors, including a number that is also involved in neurotransmission.
      Effects of Pb2+ on several of these ion channels have been investigated under
      experimental conditions that allow electrophysiological recording of membrane
      current carried by distinct types of ion channels. In whole-cell voltage clamp
      experiments voltage-dependent calcium channels are blocked by Pb2+ at micromolar
      concentrations, while voltage-dependent sodium channels are not affected by Pb2+.
      The neuronal type nicotinic acetylcholine (ACh) receptor-ion channel complex is
      sensitive to low concentrations of Pb2+. At 1 nM-3 microM, Pb2+ reduces the peak
      amplitude of the ACh-induced inward current to 74%-10% of the control value in a
      concentration-dependent manner. However, at Pb2+ concentration between 10 and 100
      microM this blocking effect is reduced and kinetics of decay of the ACh-induced
      inward current are slowed. The effects of Pb2+ on the nicotinic receptor-mediated
      inward current amplitude can be described by the sum of two sigmoidal
      concentration-effect curves with an IC50 value of 19 nM and an EC50 of 21 microM.
      The serotonin 5-HT3 receptor-ion channel complex is less sensitive to Pb2+. The
      serotonin-induced inward current is blocked by Pb2+ with an IC50 value of 49
      microM. In single channel patch clamp experiments internal Pb2+ causes activation
      of calcium-activated potassium channels in N1E-115 cells. The two types of
      calcium-activated potassium channels show differential sensitivity: the low
      conductance (SK) channel is more sensitive to Pb2+ than the high conductance (BK)
      channel. At micromolar concentrations Pb2+ also induces an ion current mediated
      by metal ion-activated ion channels. Opening of these channels, which have a
      single channel conductance of 24 pS and a reversal potential of 0 mV, depends on
      Pb2+ concentration. These effects of Pb2+ support the hypothesis that Pb2+
      affects synaptic transmission by blocking presynaptic voltage-dependent calcium
      channels. On the other hand, effects on other sensitive target sites, the
      neuronal nicotinic ACh receptor in particular, clearly indicate that other
      targets may be involved in the toxic effects of Pb2+ on the nervous system.

PMID- 7504229
TI  - Natural killer cell function and number of peripheral blood are not altered in
      recurrent aphthous ulceration.
AB  - Natural killer cell activity against K562 target cells was measured during active
      disease (within 48 hours after symptom debut, day 0), and in remission stages
      (days 14 and 28) of 10 patients with recurrent aphthous ulceration. Ten healthy
      sex- and age-matched persons with a negative history of recurrent aphthous
      ulceration served as controls. Baseline, interferon-alpha- and interleukin-2
      boosted natural killer cell activity was not significantly different between
      patients and controls at any of the three time periods. Furthermore, the
      percentages of peripheral CD16+, CD56+, and CD14+ cells were at no time
      significantly different between patients and controls. This study supports other
      investigations with respect to a systemic T-cell imbalance in which a decreased
      CD3+ and CD4+ fraction is encountered among patients with recurrent aphthous
      ulceration; however, the previously reported increase in the CD8+ subsets was not
      confirmed in the present study. Although no quantitative or nonspecific
      functional alterations of circulating peripheral natural killer cells were
      observed in patients with recurrent aphthous ulceration, this does not preclude
      NK cell involvement in the lesion sites. Furthermore, with recent studies that
      suggest a possible implication of varicella zoster virus or cytomegalovirus in
      recurrent aphthous ulceration, studies of varicella zoster virus and
      cytomegalovirus specific killer activity in this patient population are hereby
      encouraged.

PMID- 7504231
TI  - Transformation of chicken bone marrow cells by the v-ski oncogene.
AB  - The effect of the v-ski oncogene on the transformation of chicken hematopoietic
      cells was examined. In initial experiments viruses encoding the v-ski oncoprotein
      did not transform chicken bone marrow cells. However, whereas viruses encoding
      the ts-v-sea oncoprotein transform solely erythroid cells, viruses encoding both
      the v-ski and the ts-v-sea oncogenes were found capable of transforming myeloid
      cells from the monocytic and/or granulocytic lineages in addition to erythroid
      cells. Analysis of cell clones transformed by the v-ski/ts-v-sea virus identified
      one clone that no longer expressed the v-sea protein, indicating that this
      protein was necessary for the initiation but not the maintenance of
      transformation. Subsequent experiments testing the effects of various growth
      factors on transformation of bone marrow cells by the v-ski oncogene product
      alone identified the avian c-kit ligand (stem cell factor; SCF) as being able to
      co-operate with the v-ski protein to cause transformation of chicken
      hematopoietic cells of both myeloid and erythroid lineages.

PMID- 7504230
TI  - HTLV-1 tax activation of the GM-CSF and G-CSF promoters requires the interaction
      of NF-kB with other transcription factor families.
AB  - The trans-activator protein, tax, from the human T leukemia virus type 1 (HTLV-1)
      trans-activates both viral and cellular genes. It has previously been shown that
      granulocyte macrophage-colony stimulating factor (GM-CSF) is constitutively
      expressed in HTLV-1 infected cells and in cells artificially expressing tax. We
      show here that the GM-CSF promoter is tax responsive in fibroblasts and T cells,
      whereas the granulocyte (G)-CSF promoter is tax responsive only in fibroblasts.
      The tax protein can activate cellular genes through a least two families of
      transcription factors; the NF-kB/rel and CREB/ATF families. We have used mutant
      tax proteins to show that the activation of NF-kB proteins is essential for tax
      trans-activation of both the GM-CSF and G-CSF promoters. The ability of tax to
      activate CREB/ATF proteins is also essential for GM-CSF transactivation. We have
      identified a 44 bp region of the GM-CSF promoter that contains tax responsive
      elements. This region contains a classical NF-kB site, a CK-1 element that can
      bind the NF-kB p65 protein, as well as a putative ATF binding site. The tax
      response of the G-CSF promoter requires not only the conserved CK-1 sequence but
      also an adjacent NF-IL6 binding site that may explain the cell restricted
      function of the G-CSF promoter.

PMID- 7504232
TI  - Ehk-1 and Ehk-2: two novel members of the Eph receptor-like tyrosine kinase
      family with distinctive structures and neuronal expression.
AB  - We have identified two novel members of the Eph RTK family, termed Ehk (eph
      homology kinase) -1 and -2. Compared to the amino acid sequences of various Eph
      family members, Ehk-1 and Ehk-2 are closest to the Sek and Cek-4/Mek-4/Hek
      kinases, and both are more similar to the Elk kinase than they are to the Eck or
      Eph kinases. Analysis of Ehk-1 cDNAs from various brain libraries reveals
      alternatively spliced transcripts that can encode five different forms of Ehk-1
      transmembrane proteins. By contrast, Ehk-2 cDNAs revealed only a single form of
      protein coding region. However, the structure of Ehk-2 differs from all known
      members of the Eph family based on a 42 amino acid insert positioned between
      homology regions IV and V in the kinase domain. Ehk-1 and Ehk-2 are almost
      exclusively expressed in the nervous system. RNA in situ hybridization analyses
      on adult brain show that the Ehks are predominantly expressed in neurons and
      display overlapping, but distinct patterns of expression in various neuronal
      populations.

PMID- 7504233
TI  - Enhanced proliferative potential in culture of cells from p53-deficient mice.
AB  - Normal somatic cells are endowed with limited doubling potential in culture, and
      the process of immortalization is an inevitable step in neoplastic transformation
      of the cells. To examine the roles of p53 in this process, the cells of p53
      deficient mice were examined for doubling potential. Fibroblast-like cells from a
      variety of tissues of these mice proliferated continuously without showing aging
      or crisis. The aneuploid cells overcome the population with passage, but cloning
      experiment indicated that chromosomal changes were not essential to this process.
      The enhanced proliferative potential in culture of cells from the p53-deficient
      mice was also observed in epithelial cells of lens, mammary glands and seminal
      vesicles and in neural precursor cells. Proliferation of bone marrow cells in
      response to stem cell factor was enhanced in long term culture, but not in in
      vitro colony assay; no permanent cell lines could be obtained. No effects of p53
      deficiency were found in proliferation of cardiac muscle cells or hepatocytes.

PMID- 7504237
TI  - Nursing rituals: doing ethnography.
AB  - Types of nursing rituals identified in this study include therapeutic and
      occupational rituals. Therapeutic rituals (Douglas, 1963, 1966, 1975; Turner,
      1957, 1967, 1969) are identified as symbolic healing actions that improve the
      condition of patients. Occupational rituals or rituals of socialization include
      symbolic actions that facilitate the transition of professional neophytes into
      their professional role (Bosk, 1980; Fox, 1979; Zerubavel, 1979). Nursing rituals
      fulfill an important although not highly visible function in a nursing unit of a
      modern American hospital. They enable nurses to carry out caring activities for
      patients who are acutely or chronically ill, old, and dying. Rituals help to
      reaffirm values and beliefs of nurses. Explication of the implicit meanings of
      nursing rituals illuminates nursing for nurses and others who seek to understand
      nursing services. Descriptive analyses of nursing rituals direct attention to the
      hidden work of the hospital staff nurse, work sometimes taken for granted by
      professionals and the public who fail to see the many difficult, intimate, and
      risky aspects of nursing work and how certain ritual behavior promotes its
      accomplishment. Other studies on nursing ritual are needed to expand the theory
      of nursing ritual in this descriptive analysis, and to move it from descriptive
      to explanatory theory. For example, the transmission of the beliefs, rules of
      conduct, and customs that take place during change-of-shift report has not been
      extensively investigated. Neither have the more practical aspects of shift report
      been studied, including the types of information exchanged or the influence of
      shift report on planning and priority setting for the nurses who work during the
      ensuing shift. Also, few empirical studies examine the effects of bathing on
      patient outcomes, such as skin integrity, cardiac function, and comfort levels,
      and patient bathing preferences. This is surprising, because the bath is such an
      essential ritual for the nursing profession and is thought to help patients.
      Nursing's close association with profane materials, including excretions and
      secretions, has most likely affected society's perception of the role of nurse.
      Investigations about these influences may reveal valuable insights into some of
      the status problems that nurses have encountered for many years. Equally
      important is the association of nurses with death. Although nurses are frustrated
      with the intrusion of hospital technology on patients' deaths, they have not yet
      established themselves as standard setters for helping patients achieve tranquil
      deaths.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504236
TI  - Unconscious cathexis of dream symbols as measured by the Kahn Test of Symbol
      Arrangement.
AB  - This study measured unconscious cathexis and conscious association with dream
      content, using the Kahn Test of Symbol Arrangement (KTSA), with subjects
      reporting recurring, past-recurring, and nonrecurring dreams. Unconscious
      cathexis of dream content was noted for recurring dreamers; conscious association
      with dream content was not. The results suggest that the KTSA is a valuable
      instrument for the empirical study of unconscious processes and that the contents
      of recurring dreams are particularly salient in a dreamer's unconscious.

PMID- 7504235
TI  - Ribotyping shows intrafamilial similarity in Actinobacillus actinomycetemcomitans
      isolates.
AB  - This study reports ribosomal RNA gene restriction patterns of 54 Actinobacillus
      actinomycetemcomitans isolates obtained from 9 families (12 children and 11
      parents). The isolates represented serotypes a, b, c and d. The chromosomal DNA
      extracted from A. actinomycetemcomitans isolates was digested with the
      restriction endonucleases EcoRI, BamHI, HindIII, ClaI and Bg/I. The DNA fragments
      were hybridized to the rrnB ribosomal RNA operon of the Escherichia coli
      chromosome. In 5 families, isolates belonging to the same family (mother and/or
      father and the children) had identical hybridization patterns when analyzed with
      all 5 enzymes. In 3 families, each family member harbored only one ribotype of A.
      actinomycetemcomitans, but at least one member harbored isolates that were of a
      different ribotype than the other members of the family. In one family, the
      mother harbored 2 ribotypes (and serotypes), one common with the daughter and one
      different. In conclusion, the study confirms the previous results that A.
      actinomycetemcomitans is transmitted intrafamilially.

PMID- 7504238
TI  - The development of organized nursing and the Pan-American Exposition at Buffalo
      in 1901: doing historical research.

PMID- 7504234
TI  - Bilateral vocal cord paralysis with Shy-Drager syndrome.
AB  - Shy-Drager syndrome consists of progressive autonomic nervous system failure with
      Parkinson's disease-like symptoms and orthostatic hypotension. It can also result
      in airway compromise from bilateral vocal cord paralysis. Fewer than 30 cases of
      severe bilateral vocal cord paresis or paralysis associated with the Shy-Drager
      syndrome have been reported in the English literature. We present a case of a 72
      year-old man who had a 2-year history of orthostatic hypotension, neurogenic
      bladder, impotence, anhydrosis, and extremity weakness and paresthesias.
      Hoarseness and dyspnea with stridor developed as a result of bilateral vocal cord
      paralysis in the median position and required an emergency tracheotomy. This
      combination of symptoms resulted in the diagnosis of Shy-Drager syndrome. We
      present the case along with literature review of bilateral vocal cord paralysis
      with the Shy-Drager syndrome.

PMID- 7504239
TI  - HIV gene regulatory proteins tat and rev and their interactions with synthetic
      RNA.
AB  - Synthetic oligoribonucleotides have been prepared and annealed to form model RNA
      duplexes that mimic the high affinity RNA recognition sites for the HIV-1 tat and
      rev proteins. The contributions of individual functional groups on the model RNAs
      to the specificity of binding by their respective proteins were studied by use of
      oligoribonucleotides containing site-specifically modified nucleotides. Both tat
      and rev appear to recognise specifically a limited number of functional groups in
      the major groove of an RNA double helix distorted by virtue of unpaired or non
      Watson-Crick paired nucleotides.

PMID- 7504240
TI  - Inhibitory effects of 2'-deoxy-L-thymidine 5'-triphosphate on human
      immunodeficiency virus reverse transcriptase and eukaryotic DNA polymerases.
AB  - Inhibitory effects of 2'-deoxy-L-thymidine 5'-triphosphate (L-dTTP) which is an
      enantiomer of the natural substrate (D-dTTP) on the activity of mammalian DNA
      polymerases, Escherichia coli DNA polymerase I and HIV-1 reverse transcriptase
      were examined. Interestingly, L-dTTP showed remarkable inhibitory effect on HIV-1
      reverse transcriptase in competitive fashion with respect to the substrate dTTP.
      In contrast, eukaryotic cell nuclear DNA polymerases alpha and beta were not or
      slightly inhibited by L-dTTP.

PMID- 7504241
TI  - Small stable RNAs in Mycoplasma capricolum.
AB  - Five small stable RNA species have been isolated from Mycoplasma capricolum.
      Together with the previously found RNA species, M.capricolum contains at least
      six small RNAs besides rRNAs and tRNAs. The sequences of these RNAs, designated
      MCS1 to MCS6, have been determined. MCS1 RNA is homologous to 4.5S RNA of E.
      coli, MCS5 to 10Sa RNA and MCS6 to M1 RNA (RNase P RNA). Unexpectedly, MCS4 RNA
      revealed an extensive sequence similarity to eukaryotic U6 snRNAs. MCS6, 10Sa RNA
      homolog, contains a tRNA-like structure in the 5'- and 3'-terminal sequences.

PMID- 7504242
TI  - Origin of 16S and 23S rRNAs and the E. coli str operon, as derived from tandem
      tRNA repeats.
AB  - The bases 1175-1542 (3'-term.) and 94-510 of the E. coli (EC) 16S rRNA are both
      homologous to the [5S rRNA-tRNA Asn-tRNA(Ser)-tRNA(Glu)-tRNA(Val)-tRNA(Met)]
      region of the Bacillus subtilis (BSU) trrnD operon, and to the S12 and S7 r
      protein-encoding region (S12/S7 region) in the EC str operon. The 2570-2906 (3'
      term.) of the EC 23S rRNA is also homologous to the trrnD. These rRNAs had
      evolved from a str-like pre-mRNA.

PMID- 7504243
TI  - Acquirement of hairpin ribozyme activity by the long substrate-binding site.
AB  - Three hairpin ribozymes were designed to cleave Escherichia coli beta
      glucuronidase (GUS) mRNA at a target site. Two of the designed ribozymes (HG10L
      and HG10L2) had long substrate binding sites and the other (HG10) had short
      substrate binding site. All three ribozymes cleaved the substrate, and HG10L and
      HG10L2 cleaved it efficiently. However, HG10 had very low activity. Effect of
      length of substrate binding site of the ribozyme will be discussed.

PMID- 7504244
TI  - Structural studies of telomeric DNA, RNA and DNA-RNA hybrid oligonucleotides by
      non-denaturing polyacrylamide gel electrophoresis.
AB  - Five kinds of DNA, RNA and DNA-RNA hybrid oligomers(T1-T5) containing Tetrahymena
      and human telomeric sequences were synthesized. T1 is d(T2G4). T2, T3, T4 and T5
      are d(T2AG3), h(U2dG4), h(T2rG4) and r(U2G4) in sequences, respectively. Their
      structural changes were monitored by gel mobility shift on non-denaturing PAGE.
      The susceptibility of dG in telomeric structure was tested by methylation
      reaction by DMS. Our results show that telomeric DNA structure is dependent on dG
      to form intramolecular hydrogen bonding in the hairpin structure.

PMID- 7504245
TI  - Structural studies of DNA and RNA containing AG base pairs by NMR.
AB  - Base pairing between A and G residues has been suggested in some ribozymes and
      the structure derived from this non-standard base pairing could play a crucial
      role in enzymatic actions of the ribozymes. We have studied the structures of
      three DNAs and an RNA that base sequences were modeled after the ribozymes by
      NMR. It was found that the A and G residues can form a basepair in a very unique
      fashion both in the DNAs and RNA. "Side" instead of "head to head" alignment of
      the two bases was found, where an amino proton instead of an imino proton of the
      G residue is involved in the hydrogen bonding. As a result of the unique
      basepairing, certain bases stack over the bases of the opposite strand instead of
      over the ones of the same strand. It was also shown that the formation and
      thermal stability of this unique AG basepair depend on the neighbouring base
      sequences. Moreover existence of the unique AG basepairs was suggested in a real
      small metalloribozyme itself.

PMID- 7504246
TI  - Discrimination among E. coli tRNAs with a long variable arm.
AB  - In E. coli, tRNA(Ser), tRNA(Leu) and tRNA(Tyr) have a long variable arm composed
      of more than ten nucleotides (class II tRNAs). In order to study how leucyl- and
      seryl-tRNA synthetase discriminate their cognate tRNA isoacceptors from the other
      class II tRNAs, kinetic parameters of various mutated class II tRNA transcripts
      with leucyl- and seryl-tRNA synthetase were determined. Leucyl-tRNA synthetase
      recognizes A73 and A14 or its vicinity. Seryl-tRNA synthetase recognizes the long
      variable arm base-nonspecifically. C2-G71 in the acceptor stem functions as a
      negative identity element against seryl-tRNA synthetase. Difference in the
      tertiary structure among class II tRNA molecules plays a crucial role in
      discrimination by these two synthetases.

PMID- 7504247
TI  - The recognition of E. coli glutamine tRNA by glutaminyl-tRNA synthetase.
AB  - A variety of genetic, biochemical and structural studies have been used to
      determine factors ensuring the accuracy of recognition by aminoacyl-tRNA
      synthetases for tRNA. The identity elements of Escherichia coli tRNA(Gln) are
      located mainly in the anticodon and acceptor stem, and ensure the accurate
      recognition of the tRNA by glutaminyl-tRNA synthetase. We summarize a number of
      experimental techniques to define the accuracy of aminoacylation in vivo and in
      vitro.

PMID- 7504248
TI  - Identification of N4-(guanosin-7-yl)-4-aminoquinoline 1-oxide and its possible
      role in guanine C8 adduction.
AB  - A novel base adduct of the carcinogen, 4-nitroquinoline 1-oxide, N4-(guanin-7-yl)
      4-amino-quinoline 1-oxide was identified from RNA, which was bioactivated 4
      hydroxyaminoquinoline 1-oxide. In addition of base adducts, we uncovered the
      formation of 8-hydroxyguanine residue (8-OH-G) in DNA and RNA after treatment of
      4NQO, in vivo and in vitro. A conceivable mechanism of formation of 8-OH-G and
      guanine C8-substituted quinoline adducts is proposed.

PMID- 7504249
TI  - Mechanisms of the inhibition of reverse transcription by unmodified and modified
      antisense oligonucleotides.
AB  - We have demonstrated that the synthetic oligonucleotides, either unmodified or
      phosphorothioates, prevent cDNA synthesis by the AMV or HIV reverse
      transcriptases. The RNA was truncated at the antisense oligonucleotide-RNA duplex
      during the reverse transcription. Th blockage involves the degradation of the RNA
      fragment bound to the antisense oligonucleotide by the reverse transcriptase
      associated RNase H activity. However, in the case of phosphorothioate oligomer,
      the production of cDNA would be inhibited by a hybrid formed between the AMV RT
      and phosphorothioate oligomer than arrested elongation of the cDNA strands,
      whereas arrest of a growing cDNA strand by HIV RT can be blocked by an
      oligonucleotide complementary to a region downstream from the primer.

PMID- 7504250
TI  - Synthesis and properties of oligolysine and oligoglutamic acid derivatives
      containing nucleosides.
AB  - Nucleic acid analogs of L-lysine derivatives containing uridine and/or adenosine
      were synthesized. As dimer models, Lys(Urd)-Lys(Urd) and Lys(Urd)-Lys(Ado) were
      prepared by activated ester method. These dimers were found to form complex with
      poly(A), which was observed from hypochromicity of UV spectra. Furthermore,
      glutamic acid derivatives containing uridine and adenosine were also prepared.
      Oligomerization of glutamic acid derivatives were studied by Merrifield's solid
      phase synthesis.

PMID- 7504252
TI  - Hepatocellular carcinoma. Identifying and screening populations at increased
      risk.
AB  - Hepatocellular carcinoma appears to be associated with hepatitis B and C
      infections and is common in patients with cirrhosis caused by chronic viral
      hepatitis. Screening for hepatocellular carcinoma can lead to early detection and
      surgical intervention, resulting in improved survival rates. Patients with
      cirrhosis or unexplained elevation of alphafetoprotein levels should be examined
      every 3 to 6 months. Patients with chronic viral hepatitis but no underlying
      liver disease and normal levels of alpha fetoprotein may be examined yearly.
      Seronegative contacts of hepatitis B virus carriers should be immunized.

PMID- 7504251
TI  - [Concentrations of acute phase proteins in serum during the first two hours of
      hemodialysis using cuprophane and cellulose acetate dialyzers in patients with
      chronic renal failure].
AB  - In ten patients with chronic renal failure (CRF) serum concentrations of alpha 1
      acid glycoprotein, alpha 1-antitrypsin, prealbumin, hemopexin, transferrin,
      haptoglobin, C3c and C4 complement components, ceruloplasmin, alpha 2
      macroglobulin were determined using Partigen plates before, 30 min. and 2 hours
      after beginning of HD. Serum concentrations of C3c complement component,
      prealbumin increased significantly during HD using CU dialyser, but changes
      during HD using CA dialyser were not significant. Serum concentrations of alpha 1
      antitrypsin, hemopexin increased significantly after two hours of HD using CA
      dialyser, but changes during HD using CU dialyser were again not significant.
      Serum concentrations of alpha 1-acid glycoprotein, transferrin, haptoglobin,
      ceruloplasmin, C4 complement component during HD using both dialyzers did not
      change significantly. Serum concentration of alpha 2-macroglobulin was higher
      after two hours of HD. The type of dialysis membrane has important influence on
      changes of serum acute phase proteins during the initial period of HD.

PMID- 7504253
TI  - Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on open-field behaviour and
      neurochemical parameters of rats.
AB  - The effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the
      central nervous system (CNS) were studied in rats. Behavioural and neurochemical
      studies were performed. Results show that acute and oral administration of
      dimethylamine 2,4-D was able to decrease locomotion and rearing frequencies and
      to increase immobility duration of rats observed in an open-field test. Treatment
      of rats with p-chlorophenylalanine (PCPA) was unable to change rat's open-field
      behaviour; 5-hydroxytryptophan (5-HTP) administration not only increased
      locomotion and rearing frequencies but also decreased immobility duration.
      Pretreatment of the rats with PCPA and 5-HTP decreased and increased
      dimethylamine 2,4-D effects, respectively. The herbicide was not able to change
      the striatal levels of dopamine and homovanilic acid but decreased the striatal
      levels of serotonin (5-HT), as observed for the doses of 100 and 200 mg/kg and
      increased those of 5-hydroxyindoleacetic acid (5-HIAA) as measured after the 200
      mg/kg dose treatment. When the levels of serotonin and 5-HIAA were measured at
      the brain stem level, only those of 5-HIAA were modified, being increased by
      diethylamine 2,4-D (60; 100 and 200 mg/kg); this increment on 5-HIAA levels was
      observed even 1 hr after pesticide administration. Further analysis showed that
      2,4-D concentrations chromatographically detected both in serum and brain of the
      intoxicated animals were dose-dependent, being found as early as 1 hr after the
      smaller dose of the herbicide used (10 mg/kg). The results suggest that
      diethylamine 2,4-D modify 5-HT functional activity within the CNS.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7504254
TI  - Recombinant pp60c-src from baculovirus-infected insect cells: purification and
      characterization.
AB  - A simple and effective method has been developed to purify the recombinant
      protein tyrosine kinase pp60c-src from a baculovirus-insect cell expression
      system. The procedure includes affinity chromatography and HPLC. Milligram
      quantities of protein have been isolated with an activity of 3.9 mumol/min/mg
      protein using the substrate poly E4Y. This specific activity is many times higher
      than any published protocol. The enzyme is stable for months when stored in
      buffered 10% glycerol at -70 degrees C. This purification technique is compared
      to the immuno-affinity technique which is widely used for this enzyme. Enzyme
      kinetics were characterized with respect to substrate specificity, the effect of
      temperature, ionic strength, pH, and Mg+2 versus Mn+2 ions. Similar to the enzyme
      expressed in human cells, the recombinant enzyme demonstrated a higher Vmax and
      substrate specificity for poly E4Y over 5V-Agt-II. An activation energy of 14.2
      kcal/mol was determined. Inhibition by increasing ionic strength is mostly due to
      an increase in Km for the poly E4Y substrate and hence was substrate dependent.
      The Km(ATP) was pH dependent while the Km(poly E4Y) was pH independent. For the
      phosphorylation of poly E4Y, free Mg+2 was stimulatory while Mn+2 was inhibitory.
      In contrast, Mn+2 stimulated the phosphorylation of 5V-Agt-II.

PMID- 7504255
TI  - Constitutive calcium-dependent isoform of nitric oxide synthase in the human
      placental villous vascular tree.
AB  - We have characterized the NO synthase enzyme in the villous vasculature of the
      human placenta as part of our ongoing studies of the regulation of NO synthesis
      in this circulation. NO synthase activity was determined by conversion of 3H L
      arginine to 3H L-citrulline in cellular homogenate, cytosolic and particulate
      fractions. Optimal NO synthase activity was measured in all fractions in the
      presence of 1 mM NADPH, 10 microM tetrahydrobiopterin, 2 microM FAD, 100 microM
      free calcium and 50 U/ml calmodulin. The calmodulin inhibitor calmidazolium (50
      microM) and FAD inhibitor diphenyliodonium chloride (1 microM) significantly
      reduced enzyme activity. The EC50 for calcium was 0.1 microM and Km for L
      arginine 2.00 +/- 0.49 microM with Vmax 55.8 +/- 28.3 pmoles/mg protein/min.
      Enzyme activity was inhibited in both cytosolic and particulate fractions by ng
      nitro-L-arginine and ng-monomethyl-L-arginine in a concentration-dependent manner
      (10(-8)-10(-4) M). A calcium-independent NO synthase activity was also
      determined, but only constituted between 5-6 per cent of total activity. On
      Western blotting, a single 135 kda species was identified in each fraction with a
      monoclonal antibody raised against bovine aortic endothelial NO synthase. The NO
      synthase enzyme of the villous vasculature appears to correspond to the type III
      calcium-calmodulin dependent endothelial isoform.

PMID- 7504256
TI  - Distribution of alpha 2-macroglobulin and alpha 1-acid glycoprotein mRNA shows
      regional specialization in rat decidua.
AB  - In situ hybridization histochemistry was used to detect mRNA coding for the
      plasma proteins alpha 1-acid glycoprotein and alpha 2-macroglobulin in the rat
      decidua during the period when the chorioallantoic placenta is established. It
      was found that alpha 1-acid glycoprotein mRNA was localized to a subpopulation of
      decidual cells predominantly found in the decidua capsularis but extending into
      the decidua basalis at later times. The highest levels of alpha 2-macroglobulin
      mRNA were found in the decidua basalis where there was some overlap with regions
      containing alpha 1-acid glycoprotein mRNA. No alpha 2-macroglobulin mRNA could be
      found in the inner part of the decidua capsularis where the highest levels of
      alpha 1-acid glycoprotein mRNA were found. However, a thin outer layer of
      compressed stromal cells, adjacent to the myometrium expressed the alpha 2
      macroglobulin gene which surrounded the cells containing alpha 1-acid
      glycoprotein mRNA. This distribution of alpha 2-macroglobulin mRNA is consistent
      with the hypothesis that the protein is produced locally to prevent non-specific
      proteolysis which may otherwise result from catabolic processes involved in
      tissue remodelling. The function of alpha 1-acid glycoprotein is unknown but this
      protein is also likely to be involved in the maintenance of homeostasis during
      the period when contact between maternal and fetal systems is being established
      within the chorioallantoic placenta.

PMID- 7504257
TI  - Matching chemistry and shape in molecular docking.
AB  - We have added a chemical filter to the ligand placement algorithm of the
      molecular docking program DOCK. DOCK places ligands in receptors using local
      shape features. Here we label these shape features by chemical type and insist on
      complementary matches. We find fewer physically unrealistic complexes without
      reducing the number of complexes resembling the known ligand-receptor
      configurations. Approximately 10-fold fewer complexes are calculated and the new
      algorithm is correspondingly 10-fold faster than the previous shape-only
      matching. We tested the new algorithm's ability to reproduce three known ligand
      receptor complexes: methotrexate in dihydrofolate reductase, deoxyuridine
      monophosphate in thymidylate synthase and pancreatic trypsin inhibitor in
      trypsin. The program found configurations within 1 A of the crystallographic
      mode, with fewer non-native solutions compared with shape-only matching. We also
      tested the program's ability to retrieve known inhibitors of thymidylate synthase
      and dihydrofolate reductase by screening molecular databases against the enzyme
      structures. Both algorithms retrieved many known inhibitors preferentially to
      other compounds in the database. The chemical matching algorithm generally ranks
      known inhibitors better than does matching based on shape alone.

PMID- 7504258
TI  - An immunohistochemical comparison of chordoma with renal cell carcinoma,
      colorectal adenocarcinoma, and myxopapillary ependymoma: a potential diagnostic
      dilemma in the diminutive biopsy.
AB  - Chordoma is one of several similar appearing neoplasms in the retroperitoneum,
      pelvis, and abdomen with a combination of features including clear cells, with or
      without cytoplasmic vacuoles, papillary profiles, and a myxoid or myxohyaline
      stroma. The differential diagnosis of a cellular myxoid or mucinous tumor in a
      small biopsy, when the entire tumor is not available for pathologic examination,
      includes metastatic mucinous adenocarcinoma of colorectal and other similar
      appearing neoplasms, renal cell carcinoma, and myxopapillary ependymoma. We
      compared immunohistochemical reactivity of 18 chordomas with 20 colonic
      adenocarcinomas, 20 renal cell carcinomas, and six myxopapillary ependymomas
      using antibodies to vimentin, cytokeratin, epithelial membrane antigen, S100
      protein, Leu 7, glial fibrillary acidic protein, and carcinoembryonic antigen.
      All chordomas were immunoreactive for vimentin and cytokeratin, 83% for
      epithelial membrane antigen, and 83% for S100 protein. Myxopapillary ependymomas
      were distinguished by immunoreactivity for vimentin and glial fibrillary acidic
      protein in all cases and S100 protein in 50%. All colonic adenocarcinomas were
      positive for cytokeratin, epithelial membrane antigen, and carcinoembryonic
      antigen. Renal cell carcinomas were uniformly reactive for epithelial membrane
      antigen and cytokeratin, nonreactive for carcinoembryonic antigen, and variably
      reactive for S100 protein (5%) and vimentin (25%). These data indicate that a
      panel of immunohistochemical markers can be useful in distinguishing chordoma
      from potential histologic mimics.

PMID- 7504259
TI  - Idiopathic sclerosing inflammation of the orbit: immunohistologic analysis and
      comparison with retroperitoneal fibrosis.
AB  - Idiopathic sclerosing inflammation of the orbit is clinically characterized by an
      insidious, chronic and progressive fibrosing process damaging orbital structures
      through entrapment and mass effect. Histologically, desmoplasia and a sparse
      infiltrate of lymphocytes, histiocytes, plasma cells, and occasional neutrophils
      and eosinophils are seen. An immune pathogenesis is suspected but presently
      poorly understood. To characterize the inflammatory infiltrate and to compare
      orbital and other inflammatory fibrosing lesions, immunoperoxidase studies using
      the streptavidin method were performed on 16 formalin or Bouins' fixed, paraffin
      embedded orbital biopsy specimens and six specimens of retroperitoneal fibrosis.
      Positive staining of orbital tissue occurred as follows: T-cells (UCHL-1) 94% of
      cases, B-cells (L26) 40%, tissue macrophages (KP-1) 56%, HLA Dr positive antigen
      presenting cells and activated T-cells (LN3) 44%, and immunoglobulins (kappa,
      80%; lambda, 63%, IgG, 73%, IgA, 44% and IgM, 31%). Results were strikingly
      similar for retroperitoneal fibrosis. These findings imply a cell mediated
      pathogenesis in idiopathic sclerosing inflammation of the orbit that is similar
      to retroperitoneal fibrosis and suggest therapeutic potential for agents
      modifying this facet of the immune system.

PMID- 7504260
TI  - DNA flow cytometry of fresh and paraffin-embedded tissue using cytokeratin
      staining.
AB  - DNA flow cytometry measurements were performed using cytokeratin as a second
      parameter to identify epithelial cells selectively in fresh and in archival
      paraffin samples of normal and adenocarcinoma tissues from breast and colon.
      Fresh specimens consisted of 22 adenocarcinomas of breast, 20 adenocarcinomas of
      colon, 16 control breast samples, and 13 control colon samples. Paraffin block
      specimens consisted of 22 adenocarcinomas of breast (the same as fresh samples),
      20 adenocarcinomas of colon (the same as fresh samples), 37 control breast
      samples and 34 control colon samples. The average proportion of cytokeratin
      positive cells per group ranged from 31 to 55% for fresh samples and from 14 to
      34% for paraffin samples. For aneuploid cells populations of adenocarcinomas,
      which consist only of epithelial cells, the average percentage of cytokeratin
      positive cells ranged from 60 to 72%. The technique gave satisfactory
      measurements of ploidy and of cell cycle data in both types of samples. Cell
      cycle measurements were less accurate than ploidy measurements in both types of
      samples, and multiple sampling will be required for adequate accuracy. The
      average S-phase fraction of cytokeratin-positive cells ranged from 6 to 15% for
      fresh specimens and from 11 to 20% for paraffin samples. Similar data were
      obtained for the proliferative index (G1 + S + G2 + M phases). The coefficients
      of variation were smaller for proliferative index than for S-phase fraction data,
      indicating greater accuracy. Paraffin data give higher cycling cell measurements
      than corresponding fresh data, so separate standardization of measurements may be
      required for fresh and for paraffin data.

PMID- 7504261
TI  - Relationships between image cytometric DNA index, proliferation fraction and
      multiploidy and conventional nuclear grade in breast carcinoma.
AB  - High nuclear grade, DNA aneuploidy, and elevated proliferation fraction tend to
      be mutually associated in breast carcinomas, defining a subset of carcinomas with
      more aggressive behavior. We sought to examine more closely the interrelations
      between nuclear grade and DNA cytometric parameters (aneuploidy, proliferation
      fraction, and multiploidy) in breast carcinomas based on our assumption that DNA
      content is the major determinant of nuclear appearances used in grading tumors.
      We obtained estimates of the strength of correlation (correlation and contingency
      coefficients) between nuclear grade and DNA index, proliferation fraction, and
      multiploidy within a series of 87 consecutively accessioned breast carcinoma
      specimens studied by conventional histologic methods and by computer-assisted
      image analysis of Feulgen-stained imprints. Seventy-three tumors were found to
      consist of a single population of cells on the cytogram (uniploid tumors). In
      this group, DNA index of the population and proliferation fraction were
      separately compared with nuclear grade by rank-order correlation. The Spearman
      correlation coefficient (Rs) for nuclear grade versus DNA index was 0.55 (P <
      0.00006), the highest level of correlation observed between any of the parameters
      studied. Tumors given a nuclear grade of 1 were mostly diploid or near diploid,
      and Grade 3 tumors were predominantly aneuploid. However, nuclear grading did not
      effect a complete separation of diploid from aneuploid tumors, because assignment
      of intermediate grades (almost one half of the specimens) had no value in
      predicting ploidy status.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504262
TI  - Confocal laser scanning microscopy in cytopathology.
AB  - Confocal laser scanning microscopy (CLSM) has become an exciting new instrument
      with rapidly expanding potential for application to the morphological
      examination. As an initial step of examining the possible values or potentials of
      CLSM observations in diagnostic pathology materials, we applied CLSM to the
      analysis of immunolocalization of proliferating cell nuclear antigen (PCNA), p53
      and cytokeratin, and eosin and DNA fluorochrome propidium (PI) stain in cell
      smears obtained from 20 cases of squamous cell carcinoma of the esophagus.
      Superior contrasts and resolution were obtained in confocal images than in
      nonconfocal ones in immunocytochemistry, eosin, and PI stain. In
      immunocytochemistry, CLSM demonstrated subcellular localization of antigens
      examined, cytokeratin as coarse and fine intracytoplasmic fibers, PCNA as diffuse
      intranuclear localization, and p53 as heterogeneous intranuclear localization
      which appeared to be associated with chromatin structure. Optical sectioning of a
      specimen by the rejection of out-of-focus noise revealed three dimensional
      structure of cell clusters of squamous cell carcinoma. With eosin and PI as dyes
      for stain, three dimensional structures of any clusters on cell smears can be
      obtained. CLSM has vast potentials in the analysis of diagnostic cytology
      materials, including immunocytochemistry.

PMID- 7504263
TI  - Simple miniblock technique for cytology.
AB  - Seventy cytology specimens, including fine-needle aspirates from various sites,
      body effusions, and bronchoalveolar lavages were prepared with a cell block
      system. This technique, which uses a gelling reagent and a setting reagent to
      increase the recovery of material, is described in detail. Fifty-four cases had
      adequate material. To assess the efficacy of the technique, miniblock sections
      were compared with smears. In 23 cases (43%), the sections provided additional
      information for a definite diagnosis. The technique allows the recovery of minute
      cellular material and is valuable for histochemical and immunohistochemical
      studies.

PMID- 7504264
TI  - Human immunodeficiency virus infection of human brain capillary endothelial cells
      occurs via a CD4/galactosylceramide-independent mechanism.
AB  - Neuropathologic studies of AIDS patients have shown that brain capillary
      endothelial cells are a cellular target for human immunodeficiency virus (HIV) in
      vivo. We have established in vitro cultures of primary human brain capillary
      endothelial (HBCE) cells. Using this model system, we have shown a significant
      HIV infection of HBCE cells that is productive yet noncytopathic. The infection
      is mediated by a cellular interaction with gp120 that does not involve CD4 or
      galactosylceramide. HIV infection of HBCE cells may contribute to AIDS-associated
      neuropathology by disturbing the physiology of the endothelium and directly or
      indirectly facilitating dissemination of virus to the central nervous system.

PMID- 7504265
TI  - Neonatal imprinting predetermines the sexually dimorphic, estrogen-dependent
      expression of galanin in luteinizing hormone-releasing hormone neurons.
AB  - The incidence of colocalization of galanin (GAL) in luteinizing hormone-releasing
      hormone (LHRH) neurons is 4- to 5-fold higher in female than male rats. This fact
      and the finding that the degree of colocalization parallels estradiol levels
      during the estrous cycle suggest that GAL is an estrogen-inducible product in a
      subset of LHRH neurons. To analyze further this paradigm we evaluated the effects
      of gonadectomy and steroid replacement therapy in male and female rats.
      Ovariectomy resulted in a significant decrease in the number of cells
      colocalizing LHRH and GAL, whereas estradiol replacement to such animals restored
      the incidence of colocalization to that observed in controls. In males, however,
      estradiol treatment failed to enhance the incidence of colocalization of GAL and
      LHRH, indicating, therefore, that the colocalization of these peptides is gender
      determined. This possibility--i.e., gender-specific determination of LHRH neurons
      coexpressing GAL--was evaluated by neonatal manipulation of hypothalamic steroid
      imprinting. As mentioned above, male rats did not respond to estrogen or
      testosterone by increasing GAL/LHRH colocalization as females did. Neonatally
      orchidectomized rats, whose hypothalami have not been exposed to testosterone
      during the critical period, when treated with estrogen in adulthood showed an
      increase in colocalization of GAL and LHRH similar to that seen in female
      animals. These observations indicate that the colocalization of LHRH/GAL is
      neonatally determined by an epigenetic mechanism that involves the testis. In
      summary, this sex difference in the incidence of colocalization of GAL and LHRH
      represents a unique aspect of sexual differentiation in that only certain
      phenotypic characteristics of a certain cellular lineage are dimorphic. The
      subpopulation of LHRH neurons that also produces GAL represents a portion of the
      LHRH neuronal system that is sexually differentiated and programed to integrate,
      under steroidal control, a network of LHRH neurons that could synchronize their
      activity to control the estrous cycle in rats.

PMID- 7504266
TI  - Inhibition of insulitis and prevention of diabetes in nonobese diabetic mice by
      blocking L-selectin and very late antigen 4 adhesion receptors.
AB  - Leukocyte adhesion to the endothelial venules in the pancreatic islets is thought
      to be one of the initial steps in the development of insulin-dependent diabetes
      mellitus. It has been suggested that leukocyte adhesion to endothelium is a
      sequential multistep process involving various different homing receptors. We
      report here that blocking different homing receptors--namely, L-selectin and very
      late antigen 4 (VLA-4)--which function during different stages of the adhesion
      process, by specific monoclonal antibodies inhibits insulitis and prevents
      diabetes in mice. Moreover, leukocyte attachment to the inflamed vessels within
      pancreatic sections could be inhibited by anti-L-selectin and anti-VLA-4
      antibodies. Interestingly, anti-L-selectin or anti-VLA-4 antibody did not appear
      to influence the autoimmune response to a panel of pancreatic beta-cell
      autoantigens. These data suggest that L-selectin and VLA-4 receptors are involved
      in mediating leukocyte homing to the islets and that intervention of these two
      adhesion pathways may provide a novel approach for treatment of autoimmune
      diseases such as insulin-dependent diabetes mellitus.

PMID- 7504268
TI  - Ion channels induced in lipid bilayers by subvirion particles of the nonenveloped
      mammalian reoviruses.
AB  - Mechanisms by which nonenveloped viruses penetrate cell membranes as an early
      step in infection are not well understood. Current ideas about the mode for
      cytosolic penetration by nonenveloped viruses include (i) formation of a membrane
      spanning pore through which viral components enter the cell and (ii) local
      breakdown of the cellular membrane to provide direct access of infecting virus to
      the cell's interior. Here we report that of the three viral particles of
      nonenveloped mammalian reoviruses: virions, infectious subvirion particles, and
      cores (the last two forms generated from intact reovirus virions by proteolysis),
      only the infectious subvirion particles induced the formation of anion-selective,
      multisized channels in planar lipid bilayers under the experimental conditions
      used in this study. The value for the smallest size conductance varied depending
      on the lipid composition of the bilayer between 90 pS (Asolectin) and 300 pS
      (phosphatidylethanolamine:phosphatidylserine) and was found to be voltage
      independent. These findings are consistent with a proposal that the
      proteolytically activated infectious subviral particles mediate the interaction
      between virus and the lipid bilayer of a cell membrane during penetration. In
      addition, the findings indicate that the "penetration proteins" of some enveloped
      and nonenveloped viruses share similarities in the way they interact with
      bilayers.

PMID- 7504267
TI  - Mitochondrial-genome-encoded RNAs: differential regulation by corticotropin in
      bovine adrenocortical cells.
AB  - Differential screening of an adrenal cortex cDNA library for corticotropin (ACTH)
      inducible genes led to the isolation of a group of cDNAs representing
      mitochondrial genes that encode subunits of cytochrome oxidase, ATPase, and NADH
      dehydrogenase. Northern blot analysis of RNA from cells stimulated by ACTH
      confirmed the induction of these genes by ACTH yet revealed major differences in
      the relative responses of the respective mRNAs. The levels of mRNAs for
      cytochrome oxidase subunit I and ATPase increased 2- to 4-fold and for NADH
      dehydrogenase subunit 3 increased 20-fold, whereas the levels of the
      mitochondrial 16S rRNA showed no change within 6 h of ACTH stimulation. These
      effects of ACTH on mitochondrial mRNA levels probably result from both activation
      of the H2 transcription unit that encodes mitochondrial mRNAs and alteration of
      mRNA stability. ACTH also increased the activity of cytochrome oxidase after 12 h
      of stimulation. Examination of the tissue specificity of expression of five
      mitochondrial genes showed a wide range of RNA levels among 11 tissues but high
      correlations between individual RNA levels, consistent with a coordinated
      expression of the mitochondrial genes, although at different levels in each cell
      type. Proportionately high levels of mitochondrial mRNAs were found in adrenal
      cortex, probably reflecting a stimulatory effect of ACTH in vivo. Overall, the
      results indicate that ACTH enhances the energy-producing capacity of
      adrenocortical cells.

PMID- 7504269
TI  - Insulin-like growth factor binding protein 1 stimulates cell migration and binds
      to the alpha 5 beta 1 integrin by means of its Arg-Gly-Asp sequence.
AB  - Insulin-like growth factor (IGF)-binding protein 1 (IGFBP-1) contains an Arg-Gly
      Asp (RGD) integrin recognition sequence. In vitro mutagenesis was used to alter
      this RGD sequence to Trp-Gly-Asp (WGD). Migration of Chinese hamster ovary (CHO)
      cells expressing the wild-type protein was more than 3-fold greater in 48 hr
      compared with cells expressing the WGD mutant form of IGFBP-1. Similarly, wild
      type IGFBP-1 added to the media of control CHO cells stimulated migration 2-fold
      compared with the WGD protein. A synthetic RGD-containing peptide, when added to
      the medium with wild-type IGFBP-1, blocked the effect of IGFBP-1 on cell
      migration. The addition of IGF-I to the culture medium had no effect on the
      migration of cells expressing IGFBP-1 or vector alone. Affinity chromatography of
      125I-labeled CHO cell membrane proteins, using IGFBP-1 coupled to agarose,
      identified the alpha 5 beta 1 integrin (fibronectin receptor) as the only cell
      surface molecule capable of binding IGFBP-1 in an RGD-dependent manner.
      Furthermore, wild-type IGFBP-1, but not the WGD mutant form, could be
      coprecipitated from CHO cells with an antibody directed against the alpha 5
      integrin subunit. These studies demonstrate that IGFBP-1 stimulates CHO cell
      migration and binds to the alpha 5 beta 1 integrin receptor, both by an RGD
      dependent mechanism. The effect of IGFBP-1 on migration is independent of IGF-I
      and is probably mediated through the alpha 5 beta 1 integrin.

PMID- 7504270
TI  - Giant multilevel cation channels formed by Alzheimer disease amyloid beta-protein
      [A beta P-(1-40)] in bilayer membranes.
AB  - We have recently shown that the Alzheimer disease 40-residue amyloid beta-protein
      [A beta P-(1-40)] can form cation-selective channels when incorporated into
      planar lipid bilayers by fusion of liposomes containing the peptide. Since A beta
      P-(1-40) comprises portions of the putative extracellular and membrane-spanning
      domains of the amyloid precursor protein (APP751), we suggested that the channel
      forming property could be the underlying cause of amyloid neurotoxicity. The
      peptide has been proposed to occur in vivo in both membrane-bound and soluble
      forms, and we now report that soluble A beta P-(1-40) can also form similar
      channels in solvent-free lipid bilayers formed at the tip of a patch pipet, as
      well as in the planar lipid bilayer system. As in the case of liposome-mediated
      incorporation, the amyloid channel activity in the patch pipet exhibits multiple
      conductance levels between 40 and 400 pS, cation selectivity, and sensitivity to
      tromethamine (Tris). Further studies with A beta P channels incorporated into
      planar lipid bilayers from the liposome complex have also revealed that the
      channel activity can express spontaneous transitions to a much higher range of
      conductances between 400 and 4000 pS. Under these conditions, the amyloid channel
      continues to be cation selective. Amyloid channels were insensitive to
      nitrendipine at either conductance range. We calculate that if such channels were
      expressed in cells, the ensuing ion fluxes down their electrochemical potential
      gradients would be homeostatically dissipative. We therefore interpret these data
      as providing further support for the concept that cell death in Alzheimer disease
      may be due to amyloid ion-channel activity.

PMID- 7504271
TI  - Stable in vivo expression of the cystic fibrosis transmembrane conductance
      regulator with an adeno-associated virus vector.
AB  - Adeno-associated virus (AAV) vectors expressing the normal cystic fibrosis
      transmembrane conductance regulator (CFTR) cDNA complement the cystic fibrosis
      (CF) defect in vitro. Unlike other DNA virus vectors, AAV is a stably integrating
      virus, which could make possible long-term in vivo complementation of the CF
      defect in the airway epithelium. We report AAV-CFTR gene transfer and expression
      after infection of primary CF nasal polyp cells and after in vivo delivery of AAV
      CFTR vector to one lobe of the rabbit lung through a fiberoptic bronchoscope. In
      the rabbit, vector DNA could be detected in the infected lobe up to 6 months
      after administration. A 26-amino acid polypeptide sequence unique to the
      recombinant AAV-CFTR protein was used to generate both oligonucleotide probes and
      a polyclonal antibody which allowed the unambiguous identification of vector RNA
      and CFTR protein expression. With these reagents, CFTR RNA and protein were
      detected in the airway epithelium of the infected lobe for up to 6 months after
      vector administration. AAV vectors do, therefore, efficiently promote in vivo
      gene transfer to the airway epithelium which is stable over several months. These
      findings indicate that AAV-CFTR vectors could potentially be very useful for gene
      therapy.

PMID- 7504272
TI  - A conserved helix motif complements the protein kinase core.
AB  - Residues 40-300 of the mammalian catalytic (C) subunit of cAMP-dependent protein
      kinase define a conserved bilobal catalytic core shared by all eukaryotic protein
      kinases. Contiguous to the core is an extended amphipathic alpha-helix (A helix).
      Trp30, a prominent feature of this helix, fills a deep hydrophobic pocket between
      the two lobes on the surface opposite to the active site. The C subunit in
      Dictyostelium discoideum shows sequence conservation of residues 40-350 with the
      mouse enzyme but contains an N-terminal extension of 332 residues. A sequence
      corresponding to the A helix contiguous to the core is absent. However, we have
      now identified a remote A-helix motif (residues 77-98). When the core of the
      Dictyostelium C subunit was modeled, based on the mouse C subunit,
      complementarity between this putative A helix and the surface of the core was
      found to be conserved. Analysis of other protein kinases reveals that the A-helix
      motif is not restricted to cAMP-dependent protein kinase. In the Src-related
      family of protein kinases, for example, an A helix is very likely contiguous to
      the core, thus serving as a linker between the conserved catalytic core and the
      Src homology 2 domain. We predict that an A-helix motif complementary to the core
      will be a conserved feature of most eukaryotic protein kinases.

PMID- 7504273
TI  - Identification of a hexapeptide that mimics a conformation-dependent binding site
      of acetylcholine receptor by use of a phage-epitope library.
AB  - Monoclonal antibody (mAb) 5.5 is directed against the ligand-binding site of the
      nicotinic acetylcholine receptor. The epitope for this antibody is conformation
      dependent, and the antibody does not react with synthetic peptides derived from
      the receptor sequence. We have identified a ligand peptide that mimics this
      conformation-dependent epitope from a phage-epitope library composed of
      filamentous phage displaying random hexapeptides. Among 38 positive phage clones,
      individually selected from the library, 34 positive clones carried the sequence
      Asp-Leu-Val-Trp-Leu-Leu (DLVWLL), 1 positive clone had the sequence Asp-Ile-Val
      Trp-Leu-Leu (DIVWLL), and 3 positive clones expressed the sequence Leu-Ile-Glu
      Trp-Leu-Leu (LIEWLL), none of which are significantly homologous with the
      nicotinic acetylcholine receptor alpha subunit sequence. All of these phages bind
      specifically to mAb 5.5. The synthetic peptide DLVWLL inhibits binding of mAb 5.5
      to the related peptide-presenting phage and to the nicotinic acetylcholine
      receptor in a concentration-dependent manner; the IC50 value is of the order of
      10(-4) M. Bioactivity of the peptide "mimotope" DLVWLL was demonstrated in vivo
      in hatched chickens by inhibition of the mAb 5.5 effect by the peptide. The
      neuromuscular block and myasthenia gravis-like symptoms that are induced in
      chicken by passive transfer of mAb 5.5 were specifically abolished by DLVWLL.
      This study shows the potential of a random peptide phage-epitope library for
      selecting a mimotope for an antibody that recognizes a folded form of the
      protein, where peptides from the linear amino acid sequence of the protein are
      not applicable.

PMID- 7504274
TI  - Isolation of peptides that inhibit binding of basic fibroblast growth factor to
      its receptor from a random phage-epitope library.
AB  - Basic fibroblast growth factor (bFGF) is known to bind to its cell-surface
      receptors with high affinity and in a heparin-dependent manner. In an attempt to
      predict the receptor recognition site on bFGF we screened phage-epitope libraries
      with monoclonal antibodies DG2 and DE6, which inhibit bFGF binding to its
      receptor. On the affinity-isolated phages, we identified several peptide
      sequences as the putative antibody-binding epitopes on bFGF. The identified
      library epitopes shared the consensus sequence Pro-(Pro/Ser)-Gly-His-(Tyr/Phe)
      Lys, corresponding to two continuous protein sequences of bFGF: Pro-Pro-Gly-His
      Phe-Lys and Arg-Thr-Gly-Gln-Tyr-Lys at amino acids 13-18 and 120-125 of bFGF,
      respectively. Synthetic peptides of the corresponding phage epitopes or of the
      above bFGF sequences specifically inhibited binding of the antibodies to bFGF,
      blocked binding of bFGF to its high-affinity receptor, and inhibited basal and
      bFGF-induced proliferation of vascular endothelial cells at submicromolar peptide
      concentrations. The potent inhibition of bFGF binding and biological activity by
      peptides recognized by the antibodies suggests that these sequences are
      functionally involved in receptor binding and may constitute part of the receptor
      binding determinants on bFGF.

PMID- 7504275
TI  - Permeability properties of a large gated channel within the ferric enterobactin
      receptor, FepA.
AB  - FepA is an Escherichia coli outer membrane receptor protein for the siderophore
      ferric enterobactin. Prior studies conducted in vivo suggested that FepA and
      other TonB-dependent outer membrane proteins transport ligands by a gated-channel
      mechanism. To corroborate and extend these findings we have determined the
      permeability properties of the FepA channel in vitro, by measuring the diffusion
      rates of hydrophilic nonelectrolytes through the FepA channel in liposome
      swelling experiments. Like porins, the FepA deletion mutant delta RV showed a
      size-dependent permeability to oligosaccharides, indicating that it forms a
      nonspecific, hydrophilic pore. Unlike OmpF and other E. coli porins, however,
      delta RV proteoliposomes transported stachyose (666 Da) and ferrichrome (740 Da).
      These data, and other uptake results with a series of maltodextrins of increasing
      size, confirm the existence of a channel domain within FepA that is considerably
      larger than OmpF-type pores. These results represent a reconstitution of the
      channel function of a TonB-dependent receptor protein and establish that FepA
      contains the largest channel that has been characterized in the E. coli outer
      membrane.

PMID- 7504276
TI  - The phylogenetically predicted base-pairing interaction between alpha and alpha'
      is required for group II splicing in vitro.
AB  - The correct folding of group II introns apparently depends on multiple tertiary
      base-pairing interactions. Understanding the relationship between spliceosome and
      group II splicing systems ultimately requires a three-dimensional model for both
      structures. In turn, successful modeling depends at least in part on identifying
      tertiary base pairings. Sequence elements alpha and alpha' are partners in a
      potential interaction of approximately 6 base pairs that can be identified within
      domain 1 of most group II introns. In comparisons between related introns, alpha
      and alpha' maintain their potential for Watson-Crick base pairing, even though
      their primary sequences can vary [Michel, F., Umesono, K. & Ozeki, H. (1989) Gene
      82, 5-30]. Substitutions were constructed at alpha and alpha' for a block of 6
      bases each in the group II intron a5 gamma, the last intron of the COXI gene from
      the mitochondrial DNA of Saccharomyces cerevisiae. Each substitution was
      defective for self-splicing, while the compensatory double derivative was
      restored to active splicing. The alpha-alpha' interaction is required for the
      first step of splicing--that is, recognition of the 5' splice junction and
      transesterification with the branch site--since the derivative transcripts
      displayed little or no activity. The compensatory double derivative produced
      lariat introns and spliced exons with normal structures, showing that splicing
      activity and precise recognition were restored. We conclude that the alpha-alpha'
      base pairing is necessary for efficient self-splicing by intron a5 gamma under
      several conditions. This result also provides an additional constraint for any
      three-dimensional model of group II intron structure.

PMID- 7504277
TI  - The gene for congenital chloride diarrhea maps close to but is distinct from the
      gene for cystic fibrosis transmembrane conductance regulator.
AB  - Congenital chloride diarrhea (CLD) is characterized by watery stools with high
      chloride content beginning prenatally and is inherited as an autosomal recessive
      trait. Perfusion studies have established a basic defect in ileal and colonic Cl
      /HCO3- transport, resulting in defective chloride absorption. The protein and its
      gene defects have, however, remained uncharacterized. We attempted to exclude
      candidate genes by considering linkage disequilibrium as well as genetic linkage
      in a small number of Finnish families. Initial results were suggestive of linkage
      between CLD and the cystic fibrosis transmembrane regulator gene (CFTR). Extended
      analysis in eight families confirmed close linkage to chromosome 7 markers
      proximal of CFTR, with maximum logarithm of odds scores of 5.11 and 5.06 for
      D7S501 and D7S496, respectively, at zero recombination. Allelic associations were
      observed that were striking between CLD and D7S496 and weaker between CLD and
      D7S501. Multipoint analyses mapped CLD unequivocally at D7S496 with a maximum
      logarithm of odds score of 9.33. We conclude that the CLD gene maps close to, but
      is distinct from, CFTR.

PMID- 7504279
TI  - Generation and screening of an oligonucleotide-encoded synthetic peptide library.
AB  - We have prepared a library of approximately 10(6) different peptide sequences on
      small, spherical (10-microns diameter) beads by the combinatorial chemical
      coupling of both L- and D-amino acid building blocks. To each bead is covalently
      attached many copies of a single peptide sequence and, additionally, copies of a
      unique single-stranded oligonucleotide that codes for that peptide sequence. The
      oligonucleotide tags are synthesized through a parallel combinatorial procedure
      that effectively records the process by which the encoded peptide sequence is
      assembled. The collection of beads was screened for binding to a fluorescently
      labeled anti-peptide antibody using a fluorescence-activated cell sorting
      instrument. Those beads to which the antibody bound tightly were isolated by
      fluorescence-activated sorting, and the oligonucleotide identifiers attached to
      individual sorted beads were amplified by the PCR. Sequences of the amplified
      DNAs were determined to reveal the identity of peptide sequences that bound to
      the antibody with high affinity. By combining the capacity for information
      storage in an oligonucleotide code with the tremendous level of amplification
      possible through the PCR, we have devised a means for specifying the identity of
      each member of a vast library of molecules synthesized from both natural and
      unnatural chemical building blocks. In addition, we have shown that the use of
      flow cytometry instrumentation permits facile isolation of individual beads that
      bear high-affinity ligands for biological receptors.

PMID- 7504278
TI  - The human myelin basic protein gene is included within a 179-kilobase
      transcription unit: expression in the immune and central nervous systems.
AB  - Two human Golli (for gene expressed in the oligodendrocyte lineage)-MBP (for
      myelin basic protein) cDNAs have been isolated from a human oligodendroglioma
      cell line. Analysis of these cDNAs has enabled us to determine the entire
      structure of the human Golli-MBP gene. The Golli-MBP gene, which encompasses the
      MBP transcription unit, is approximately 179 kb in length and consists of 10
      exons, seven of which constitute the MBP gene. The human Golli-MBP gene contains
      two transcription start sites, each of which gives rise to a family of
      alternatively spliced transcripts. At least two Golli-MBP transcripts, containing
      the first three exons of the gene and one or more MBP exons, are produced from
      the first transcription start site. The second family of transcripts contains
      only MBP exons and produces the well-known MBPs. In humans, RNA blot analysis
      revealed that Golli-MBP transcripts were expressed in fetal thymus, spleen, and
      human B-cell and macrophage cell lines, as well as in fetal spinal cord. These
      findings clearly link the expression of exons encoding the
      autoimmunogen/encephalitogen MBP in the central nervous system to cells and
      tissues of the immune system through normal expression of the Golli-MBP gene.
      They also establish that this genetic locus, which includes the MBP gene, is
      conserved among species, providing further evidence that the MBP transcription
      unit is an integral part of the Golli transcription unit and suggest that this
      structural arrangement is important for the genetic function and/or regulation of
      these genes.

PMID- 7504280
TI  - Expression of a Pim-1 transgene accelerates lymphoproliferation and inhibits
      apoptosis in lpr/lpr mice.
AB  - Transgenic mice expressing the Pim-1 kinase are predisposed to develop T-cell
      lymphomas with a long latency period of about 7-9 months. However, the exact
      functional basis of the oncogenic activity of Pim-1 remains obscure. C57BL/6 mice
      homozygous for the lpr mutation develop a well-described lymphoproliferative
      syndrome at about 26-30 weeks of age. This syndrome is characterized mainly by
      the accumulation of abnormal T cells in lymph nodes because of the lack of Fas
      receptor-induced apoptosis. We find that backcross of E mu-Pim-1 transgenics
      (mice with a transgene that carries the mouse Pim-1 gene under the
      transcriptional control of the immunoglobulin heavy chain gene enhancer E mu)
      into lpr/lpr mice results in strong acceleration of lymphoproliferation and
      dramatic enlargement of lymph nodes. In addition, we show here that cultured
      lymph node cells from E mu-Pim-1 lpr/lpr mice are rescued from rapid apoptosis
      that normally occurs in nontransgenic lpr cells in vitro. We also present
      evidence that CD4+/CD8+ double-positive thymocytes from lpr/lpr mice are
      sensitive to dexamethasone-induced apoptosis, although lpr/lpr mice lack the Fas
      receptor. In contrast, E mu-Pim-1 lpr/lpr animals show considerable protection
      from dexamethasone-induced apoptosis. These results show that Pim-1 can strongly
      accelerate lymphoproliferation through inhibition of apoptosis and thereby
      provide first insight into the functional basis for the oncogenic activity of Pim
      1.

PMID- 7504281
TI  - Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated
      in colorectal carcinomas.
AB  - Biliary glycoprotein (BGP) is the human homologue of a cell adhesion molecule
      (CAM) of the rat designated Cell-CAM. The BGP gene is a member of the
      carcinoembryonic antigen gene family, which belongs to the immunoglobulin
      superfamily. BGP is expressed in cells of epithelial and myeloid origin. In
      granulocytes, BGP is a main antigen of the CD66 cluster of differentiation
      antigens that mediate the binding to endothelial E-selectin. Since BGP is a major
      human CAM, the expression of BGP was studied in 21 colorectal carcinoma tissue
      specimens and in the respective adjacent normal mucosae. As an internal control
      for epithelial mRNA, the expression of cytokeratin 18 was evaluated in parallel.
      In addition, the expression of carcinoembryonic antigen and nonspecific
      crossreacting antigen, which are highly homologous to BGP, was investigated. Two
      BGP mRNAs of 3.9 and 1.5 kilobases were detected in the normal colonic mucosa
      samples. The median of the tumor-to-normal ratios of mRNA expression was 0.2 for
      both BGP mRNAs. In contrast, the median was 1.2 for cytokeratin, 1.0 for
      carcinoembryonic antigen, and 1.4 for nonspecific crossreacting antigen. Relative
      to cytokeratin 18 expression, the expression of BGP was reduced to < or = 0.1 in
      half of the tumors and to < or = 0.4 in > 80% of the tumors. These findings
      indicate that the loss or reduced expression of the adhesion molecule BGP is a
      major event in colorectal carcinogenesis.

PMID- 7504282
TI  - Nitric oxide synthases reveal a role for calmodulin in controlling electron
      transfer.
AB  - Nitric oxide (NO) is synthesized within the immune, vascular, and nervous
      systems, where it acts as a wide-ranging mediator of mammalian physiology. The NO
      synthases (EC 1.14.13.39) isolated from neurons or endothelium are calmodulin
      dependent. Calmodulin binds reversibly to neuronal NO synthase in response to
      elevated Ca2+, triggering its NO production by an unknown mechanism. Here we show
      that calmodulin binding allows NADPH-derived electrons to pass onto the heme
      group of neuronal NO synthase. Calmodulin-triggered electron transfer to heme was
      independent of substrate binding, caused rapid enzymatic oxidation of NADPH in
      the presence of O2, and was required for NO synthesis. An NO synthase isolated
      from cytokine-induced macrophages that contains tightly bound calmodulin
      catalyzed spontaneous electron transfer to its heme, consistent with bound
      calmodulin also enabling electron transfer within this isoform. Together, these
      results provide a basis for how calmodulin may regulate NO synthesis. The ability
      of calmodulin to trigger electron transfer within an enzyme is unexpected and
      represents an additional function for calcium-binding proteins in biology.

PMID- 7504283
TI  - Proteolytic processing and membrane association of putative nonstructural
      proteins of hepatitis C virus.
AB  - By using a plasmid-based transient protein expression system in cultured cells
      and an in vitro transcription/translation system, we analyzed the proteolytic
      processing of the putative nonstructural protein region of the precursor
      polyprotein from a Japanese type of hepatitis C virus. In addition to the
      previously reported viral proteins, p21 and p70, we identified products of 4 kDa
      (p4), 27 kDa (p27), 56 kDa (p56), 58 kDa (p58), and 66 kDa (p66). These products
      were produced in a viral serine proteinase (proteinase 2)-dependent manner from
      the region downstream of p70 in the precursor polyprotein and were arranged as
      NH2-p70-p4-p27-p58(p56)-p66-COOH as determined with region-specific antibodies.
      We showed that p56 was an N-terminally truncated form of p58, which suggested
      that a small polypeptide of 2 kDa (p2) was produced from the N-terminal part of
      p58. Cleavage between p4 and p27 was inefficient in vitro and we saw the 31-kDa
      precursor polypeptide (p31) accumulate. Furthermore, efficient cleavage at this
      site in vivo required the presence of p58/p56. Immunoprecipitation analysis in
      vitro also suggested the mutual interaction of those nonstructural protein
      products. An especially close association of p4 with p70 may contribute to
      association of p70 with microsomal membranes.

PMID- 7504285
TI  - A positive addition to a negative tail's tale.

PMID- 7504284
TI  - Myelin protein zero gene mutated in Charcot-Marie-tooth type 1B patients.
AB  - Autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B
      (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study
      the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb
      centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a
      major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B
      family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients
      converts a positively charged lysine in codon 96 to a negatively charged
      glutamate. The same MPZ locus cosegregates with the CMT1B disease gene in a
      second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at theta =
      0.00] with a splice junction mutation. Both mutations occur in MPZ protein
      regions otherwise conserved identically in human, rat, and cow since these
      species diverged 100 million years ago. MPZ protein, expressed exclusively in
      myelinated peripheral nerve Schwann cells, constitutes > 50% of myelin protein.
      These mutations are anticipated to disrupt homophilic MPZ binding and result in
      CMT1B peripheral nerve demyelination.

PMID- 7504286
TI  - Complex synthetic chemical libraries indexed with molecular tags.
AB  - Combinatorial methods of chemical synthesis allow the creation of molecular
      libraries having immense diversity. The utility of such libraries is dependent
      upon identifying the structures of the molecules so prepared. We describe the
      construction of a peptide combinatorial library, having 117,649 different
      members, synthesized on beads and indexed with inert chemical tags. These tags
      are used as a binary code to record the reaction history of each bead. The code
      can be read directly from a single bead by electron capture capillary gas
      chromatography. We demonstrate the correct selection of members of the library on
      the basis of binding to a monoclonal antibody.

PMID- 7504287
TI  - Ribozyme cleaves rex/tax mRNA and inhibits bovine leukemia virus expression.
AB  - Bovine leukemia virus (BLV) encodes at least two regulatory proteins, Rex and
      Tax. Tax, the transactivating protein, stimulates the long terminal repeat to
      promote viral transcription and may be involved in tumorigenesis. Rex is involved
      in the transition from early expression of regulatory proteins to later
      expression of viral structural proteins. We have targeted ribozymes against the
      mRNA encoding Rex and Tax. The ribozymes consist of the hammer-head catalytic
      motif flanked by antisense sequences that hybridize with the complementary
      rex/tax mRNA. To evaluate cleavage in a cell-free system, we transcribed portions
      of rex/tax mRNA and incubated them with synthetic RNA ribozymes. A ribozyme was
      identified that cleaves > 80% of the target RNA. Synthetic DNA encoding this
      ribozyme was cloned into the expression vector pRc/RSV and transfected into BLV
      infected bat lung cells. Intracellular cleavage of rex/tax mRNA was confirmed by
      reverse transcriptase PCR. In cells expressing the ribozyme, viral expression was
      markedly inhibited. Expression of the BLV core protein p24 was inhibited by 61%,
      and reverse transcriptase activity in supernatant was inhibited by 92%. Ribozyme
      inhibition of BLV expression suggests that cattle expressing these sequences may
      be able to control BLV replication.

PMID- 7504288
TI  - Cytokinin stimulates dihydropyridine-sensitive calcium uptake in moss
      protoplasts.
AB  - Ca2+ influx through dihydropyridine (DHP)-sensitive Ca2+ channels is thought to
      be an early event in cytokinin-induced bud formation in moss protonema because
      DHP antagonists inhibit bud formation in the presence of cytokinin and DHP
      agonists stimulate bud formation in the absence of cytokinin [Conrad, P. A. &
      Helper, P. K. (1988) Plant Physiol. 86, 684-687]. In the present study, we
      established the presence of a DHP-sensitive Ca2+ transport system by measuring
      45Ca2+ influx into moss protoplasts. Ca2+ influx was stimulated by external KCl
      (up to 5 mM), indicating that transport is voltage-dependent. K(+)-induced Ca2+
      influx was DHP-sensitive with > 50% inhibition at 500 nM nifedipine. Ca2+ influx
      was stimulated by increasing concentrations of the DHP Ca2+ channel agonist Bay
      K8644 with half-maximal effects at 25 nM; this stimulation was seen only in the
      absence of K+, suggesting that the agonist works preferentially on polarized
      membranes. Ca2+ influx was also inhibited by phenylalkylamines (verapamil) and
      benzothiazepines (diltiazem). The phytohormone 6-benzylaminopurine consistently
      stimulated Ca2+ influx with a Km value of 1 nM, whereas adenine, indoleacetic
      acid, and gibberellic acid had no effect on Ca2+ transport. The cytokinins
      kinetin and trans-zeatin caused a greater stimulation of Ca2+ influx and induced
      more bud formation than did 6-benzylaminopurine. These results indicate that Ca2+
      is taken up into moss protoplasts through voltage-dependent DHP-sensitive Ca2+
      channels on the plasma membrane and that one of the cytokinin effects in the
      induction of bud formation is regulation of this plasma membrane Ca2+ channel.

PMID- 7504289
TI  - Human bradykinin B2 receptors isolated by receptor-specific monoclonal antibodies
      are tyrosine phosphorylated.
AB  - We report the immunoaffinity isolation of bradykinin B2 receptors in a tyrosine
      phosphorylated state from WI-38 human lung fibroblasts. We generated six
      monoclonal antibodies directed against B2 bradykinin receptor biologic activity
      mediating prostaglandin E2 production in WI-38. These cells express a repertoire
      of bradykinin receptor affinity forms with closely correlated biologic activity
      and [3H]bradykinin binding. Some of the monoclonal antibodies selectively
      recognize intermediate-affinity (Kd = 5.6 nM) or low-affinity (Kd = 42 nM)
      receptor forms, whereas others recognize epitopes common to both. The monoclonal
      antibodies block bradykinin binding and biologic activity. Immunoaffinity
      chromatography on an immobilized monoclonal antibody of intermediate- plus low
      affinity specificity yields WI-38 B2 receptors with intact [3H]bradykinin binding
      activity and a molecular mass of 78 kDa. The same band is immunoblotted by all
      the monoclonal antibodies, indicating a similar molecular mass for receptor forms
      of different affinity. Anti-phosphotyrosine antibodies demonstrate that the
      receptors are tyrosine phosphorylated, with implications for receptor function
      and regulation. Genistein completely inhibits bradykinin-mediated prostaglandin
      E2 production with an IC50 of 8 microM, indicating that tyrosine kinase activity
      is critical for the signal transduction leading to arachidonic acid release.

PMID- 7504290
TI  - spoT-dependent accumulation of guanosine tetraphosphate in response to fatty acid
      starvation in Escherichia coli.
AB  - We previously isolated a mutant of Escherichia coli that is preferentially
      affected in the synthesis of rRNA and has a mutation in the gene (accD) encoding
      a subunit of acetyl-CoA carboxylase. Using this mutant and other mutants of the
      pathway for fatty acid and phospholipid biosynthesis as well as cerulenin, a
      specific inhibitor of fatty acid synthesis, we show that (i) inhibition of fatty
      acid synthesis in the presence of both a carbon source and all 20 amino acids
      stimulates the accumulation of guanosine tetraphosphate (ppGpp) and leads to
      preferential inhibition of rRNA synthesis, (ii) this ppGpp accumulation is spoT
      dependent, and (iii) the generation of the metabolic signal that stimulates this
      spoT-mediated response probably does not depend on either phospholipid starvation
      or a significant reduction in the level of ATP.

PMID- 7504291
TI  - Transformation of human T-cell clones by Herpesvirus saimiri: intact antigen
      recognition by autonomously growing myelin basic protein-specific T cells.
AB  - Herpesvirus saimiri has recently been shown to immortalize human T cells. It was
      unknown, however, whether Herpesvirus saimiri transformation affects T-cell
      receptor (TCR) expression and signal transduction. In the present study, we have
      transformed CD4+ human T-cell clones specific for human myelin basic protein. The
      transformed T cells were grown in interleukin 2 and divided in the absence of
      antigen and antigen-presenting cells. They retained the membrane phenotype of
      activated T cells and secreted the cytokines interferon gamma and lymphotoxin,
      but interleukin 4 was not detected. Further, the transformed T cells continued to
      express the original TCR as demonstrated by TCR variable-region-V beta-specific
      monoclonal antibodies and TCR sequencing. Antigen-specific recognition and signal
      transduction by the TCR were demonstrated by myelin-basic-protein-induced HLA-DR
      restricted secretion of interferon gamma and lymphotoxin and by myelin-basic
      protein-specific proliferation. Antigen specificity and reactivity have been
      maintained for > 1 year after transformation. Transformation with Herpesvirus
      saimiri now allows the production of virtually unlimited numbers of (auto)antigen
      specific T cells expressing functional TCR and a stable membrane phenotype. This
      technology will facilitate studies of the pathogenesis of putative autoimmune
      diseases, such as multiple sclerosis, and may be of help in TCR-targeted
      immunotherapy.

PMID- 7504292
TI  - Expression and functional significance of an additional ligand for CTLA-4.
AB  - Effective T-cell activation requires antigen/major histocompatibility complex
      engagement by the T-cell receptor complex in concert with one or more
      costimulatory molecules. Recent studies have suggested that the B7 molecule,
      expressed on most antigen presenting cells, functions as a costimulatory molecule
      through its interaction with CD28 on T cells. Blocking the CD28/B7 interaction
      with CTLA4Ig inhibits T-cell activation in vitro and induces unresponsiveness. We
      demonstrate that another molecule(s), termed B7-2, is expressed constitutively on
      dendritic cells, is differentially regulated on B cells, and costimulates naive T
      cells responding to alloantigen. B7-2 is up-regulated by lipopolysaccharide in <
      6 hr and is maximally expressed on the majority of B cells by 24 hr. In contrast,
      B7 is detected only on a subset of activated B cells late (48 hr) after
      stimulation. In addition, Con A directly induces B7-2 but not B7 expression on B
      cells. Finally, although both anti-B7 monoclonal antibodies and CTLA4Ig blocked T
      cell proliferation to antigen-expressing B7 transfectants, only CTLA4Ig had any
      significant inhibitory effect on T-cell proliferation to antigens expressed on
      natural antigen presenting cells, such as dendritic cells. Thus, B7 is not the
      only costimulatory molecule capable of initiating T-cell responses since a second
      ligand, B7-2, can provide a necessary second signal for T-cell activation.

PMID- 7504293
TI  - Activated human B lymphocytes express three CTLA-4 counterreceptors that
      costimulate T-cell activation.
AB  - Signaling via the T-cell receptor complex is necessary but not sufficient to
      induce antigen-specific T lymphocytes to expand clonally. To proliferate, T cells
      must receive one or more costimulatory signals provided by antigen presenting
      cells (APCs). One such critical costimulatory signal is delivered by the
      CD28/CTLA-4 counterreceptor, B7, expressed on APCs. B7 costimulation induces CD28
      signaling, resulting in interleukin 2 (IL-2) secretion, and T-cell proliferation.
      Conversely, T-cell receptor signaling in the absence of B7 costimulation results
      in induction of antigen-specific tolerance. Here, we show that activated human B
      lymphocytes express two additional CTLA-4 counterreceptors also capable of
      providing T-cell costimulation. At 24 hr postactivation, B cells express a CTLA-4
      counterreceptor not recognized by anti-B7 or -BB-1 monoclonal antibodies (mAbs),
      which induces detectable IL-2 secretion and T-cell proliferation. At 48 and 72 hr
      postactivation, B cells express both B7 and a third CTLA-4 counterreceptor
      identified by the anti-BB-1 mAb. BB-1 appears to be a molecule distinct from B7
      by its expression on B7- cells and its capacity to induce T cells to proliferate
      without significant accumulation of IL-2. As observed for B7, costimulatory
      signals mediated by these alternative CTLA-4/CD28 counterreceptors are likely to
      be essential for generation of an immune response and their absence may result in
      antigen-specific tolerance. We propose the following terminology for these CTLA-4
      counterreceptors: (i) B7, B7-1; (ii) early CTLA-4 binding counterreceptor, B7-2;
      and (iii) BB-1, B7-3.

PMID- 7504294
TI  - Costimulation of T-cell activation and virus production by B7 antigen on
      activated CD4+ T cells from human immunodeficiency virus type 1-infected donors.
AB  - Infection with the human immunodeficiency virus type 1 (HIV-1) requires T-cell
      activation. Recent studies have shown that interactions of the T-lymphocyte
      receptors CD28 and CTLA-4 with their counter receptor, B7, on antigen-presenting
      cells are required for optimal T-cell activation. Here we show that HIV-1
      infection is associated with decreased expression of CD28 and increased
      expression of B7 on CD4+ T-cell lines generated from seropositive donors by
      alloantigen stimulation. Loss of CD28 expression was not seen on CD4+ T-cell
      lines from seronegative donors, but up-regulation of B7 expression was observed
      upon more prolonged culture. Both T-cell proliferation and interleukin 2 mRNA
      accumulation in HIV-1-infected cultures required costimulation with exogenous B7
      because these events were blocked by CTLA4Ig, a soluble form of CTLA-4 that binds
      B7 with high avidity. In contrast, levels of HIV-1 RNA were not affected by
      CTLA4Ig, indicating that regulation of virus transcription in these cultures did
      not depend upon CD28-B7 engagement. Infected T cells could present alloantigen to
      fresh, uninfected CD4+ T cells, leading to increased proliferation and virus
      spread to the activated cells. Both of these events were blocked by CTLA4Ig.
      Thus, chronic activation of HIV-1-infected CD4+ T cells reduces expression of
      CD28 and increases expression of B7, thereby enabling these T cells to become
      antigen-presenting cells for uninfected CD4+ T cells; this might be another
      mechanism for HIV-1 transmission via T-cell-T-cell contact.

PMID- 7504295
TI  - The receptor for interleukin 3 is selectively induced in human endothelial cells
      by tumor necrosis factor alpha and potentiates interleukin 8 secretion and
      neutrophil transmigration.
AB  - Interleukin (IL)-3 stimulates hemopoiesis in vitro. However, IL-3 is not normally
      found in bone marrow, raising doubts as to the in vivo role of IL-3. We have
      found that human umbilical vein endothelial cells (HUVEC) express functional high
      affinity receptors for IL-3 after stimulation with tumor necrosis factor alpha
      (TNF-alpha), IL-1 beta, or lipopolysaccharide, and that this receptor is involved
      in inflammatory phenomena. TNF-alpha caused time- and dose-dependent up
      regulation of mRNA for the IL-3 receptor alpha and beta chains, with maximal
      effects occurring 16-36 h after stimulation with TNF-alpha at 100 units/ml.
      Induction of mRNA correlated with protein expression on the cell surface as
      judged by monoclonal antibody staining and by the ability of HUVEC to
      specifically bind 125I-labeled IL-3. Scatchard analysis under optimal conditions
      of TNF-alpha stimulation revealed approximately 1500 IL-3 receptors per cell,
      which were of a high-affinity class (Kd = 500 pM) only. In contrast to a previous
      report, receptors for granulocyte-macrophage colony-stimulating factor could not
      be detected. IL-3 binding to TNF-alpha-activated HUVEC enhanced IL-8 production,
      E-selection expression, and neutrophil transmigration. The selective induction of
      a functional IL-3 receptor on endothelial cells suggests that, beyond
      hemopoiesis, IL-3 may have an important role in chronic inflammation and in
      allergic diseases.

PMID- 7504296
TI  - Nitric oxide is a mediator of the decrease in cytochrome P450-dependent
      metabolism caused by immunostimulants.
AB  - Bacterial lipopolysaccharide (LPS) and a diverse array of other immunostimulants
      and cytokines suppress the metabolism of endogenous and exogenous substances by
      reducing activity of the hepatic cytochrome P450 mixed-function oxidase system.
      Although this effect of immunostimulants was first described almost 40 yr ago,
      the mechanism is obscure. Immunostimulants are now known to cause NO
      overproduction by cells via induction of nitric oxide synthase. We have
      investigated whether NO overproduction is involved in suppressing hepatic
      metabolism by LPS. In vitro treatment of hepatic microsomes with NO, produced by
      chemical decomposition of 3-morpholinosydnonimine or by nitric oxide synthase,
      substantially suppressed cytochrome P450-dependent oxygenation reactions. This
      effect of NO was seen with hepatic microsomes prepared from two species (rat and
      chicken) and after exposure to chemicals that induce distinct molecular isoforms
      of cytochromes P450 (beta-naphthoflavone, 3-methylcholanthrene, and
      phenobarbital). Spectral studies indicate that NO reacts in vitro with both
      Fe(2+)- and Fe(3+)-hemes in microsomal cytochromes P450. In vivo, LPS diminished
      the phenobarbital-induced dealkylation of 7-pentoxyresorufin by rat liver
      microsomes and reduced the apparent P450 content as measured by CO binding. These
      LPS effects were associated with induction of NO synthesis; LPS-induced NO
      synthesis showed a strong positive correlation with the severity of cytochrome
      P450 inhibition. The decrease in both hepatic microsomal P450 activity and CO
      binding caused by LPS was largely prevented by the selective NO synthase
      inhibitor N omega-nitro-L-arginine methyl ester. Our findings implicate NO over
      production as a major factor mediating the suppression of hepatic metabolism by
      immunostimulants such as LPS.

PMID- 7504297
TI  - Tyrosine phosphorylation of mammalian RNA polymerase II carboxyl-terminal domain.
AB  - The carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II is
      composed of tandem repeats of the consensus sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser.
      Phosphorylation of the CTD occurs during formation of the initiation complex and
      is correlated with the transition from complex assembly to elongation.
      Previously, serine and threonine residues within the CTD have been shown to be
      modified by the addition of phosphate and by the addition of O-linked GlcNAc. Our
      results establish that the CTD is also modified in vivo by phosphorylation on
      tyrosine. Furthermore, a nuclear tyrosine kinase encoded by the c-abl
      protooncogene phosphorylates the CTD to a high stoichiometry in vitro. Under
      conditions of maximum phosphorylation, approximately 30 mol of phosphate are
      incorporated per mol of CTD. The observation that the CTD is not phosphorylated
      by c-Src tyrosine kinase under identical conditions indicates that the CTD is not
      a substrate of all tyrosine kinases. Phosphorylation of tyrosine residues within
      the CTD may modulate the interaction of RNA polymerase II with the preinitiation
      complex and, hence, may be important in regulating gene expression.

PMID- 7504298
TI  - Activation of phosphotyrosine phosphatase activity by reduction of cell-substrate
      adhesion.
AB  - Treatment of chicken embryo fibroblasts (CEFs) with trypsin results in a dose-
      and time-dependent loss of phosphotyrosine from cellular proteins. A similar, but
      less marked, reduction in protein tyrosine phosphorylation occurs upon incubation
      of CEFs in phosphate-buffered saline (PBS). The decrease in the phosphotyrosine
      content of proteins following treatment with trypsin or PBS, as determined by
      immunoblotting of cell extracts with anti-phosphotyrosine antibodies, corresponds
      with a loss of phosphotyrosine antibody immunoreactivity at focal contacts, as
      detected by immunofluorescence microscopy. The recovery of phosphotyrosine in
      cellular proteins occurs within 30 min following removal of trypsin, even in the
      presence of the protein synthesis inhibitor cycloheximide, indicating that the
      loss of phosphotyrosine-containing proteins is not due to their degradation by
      trypsin. Pretreatment of CEFs with inhibitors of protein-tyrosine-phosphatases
      greatly reduces the loss of phosphotyrosine from proteins brought about by
      trypsin. In addition, phosphotyrosine phosphatase activity is increased in
      extracts prepared from trypsin-treated CEFs. The loss of phosphotyrosine from
      proteins following treatment with trypsin or PBS is not specific to CEFs but is
      also observed in established fibroblast lines. Taken together these results
      suggest that the activity of one or more phosphotyrosine phosphatases is
      regulated by cell-substrate adhesion.

PMID- 7504299
TI  - Evidence for an additional ligand, distinct from B7, for the CTLA-4 receptor.
AB  - Activation of T lymphocytes requires the recognition of peptide-major
      histocompatibility complex complexes and costimulatory signals provided by
      antigen-presenting cells (APCs). The best-characterized costimulatory molecule to
      date is the B7 antigen, a member of the immunoglobulin family that binds two
      receptors, CD28 and CTLA-4, expressed on the T-cell surface. Using the anti-mouse
      B7 (mB7) monoclonal antibody (mAb) 16-10A1, which we recently developed, we found
      that mB7 is indeed an important costimulatory ligand for the antigen-specific
      activation of murine T cells by B lymphocytes. Three lines of evidence suggest,
      however, the existence of at least one additional ligand for the CTLA-4 receptor.
      First, a soluble fusion protein of human CTLA-4 and the IgG1 Fc region, termed
      CTLA4Ig, blocks better than the anti-mB7 mAb the allogeneic stimulation of T
      cells by unfractionated splenic APCs. Second, saturating amounts of anti-mB7 mAb
      do not significantly block binding of fluorescein isothiocyanate-conjugated
      CTLA4Ig to activated splenic APCs. Furthermore, CTLA4Ig but not the anti-mB7 mAb
      reacts with the M12 and M12.C3 cell lines. The identification of an additional
      ligand for CTLA-4 may have applications to the treatment of autoimmune disease
      and transplant-associated disorders.

PMID- 7504300
TI  - High-affinity RNA ligands to basic fibroblast growth factor inhibit receptor
      binding.
AB  - We have isolated RNA ligands with low-nanomolar affinity and high specificity to
      basic fibroblast growth factor from a pool of 10(14) molecules containing 30
      randomized positions by the systematic evolution of ligands by exponential
      enrichment (SELEX) procedure. High-affinity ligands could be classified into two
      families based on sequence and secondary structure similarities. Representative
      RNA ligands from the two families compete with one another as well as with
      heparin for binding to the protein. Furthermore, we show that these ligands
      inhibit the first step in the signaling pathway of basic fibroblast growth
      factor: binding of the growth factor to its cell-surface receptors. These
      findings emphasize the general usefulness of SELEX as a tool for discovering
      potent, specific oligonucleotide antagonists of target proteins.

PMID- 7504301
TI  - Galanin-receptor ligand M40 peptide distinguishes between putative galanin
      receptor subtypes.
AB  - The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds
      with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal,
      hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat
      insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that
      M40 (1 microM) displaces [mono[125I]iodo-Tyr26]galanin from binding sites in the
      hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent
      galanin-receptor antagonist: M40, in doses comparable to that of galanin,
      antagonizes the stimulatory effects of galanin on feeding, and it blocks the
      galaninergic inhibition of the scopolamine-induced acetylcholine release in the
      ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both
      the galanin-mediated inhibition of the glucose-induced insulin release in
      isolated mouse pancreatic islets and the inhibitory effects of galanin on the
      forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F cells; instead M40 is
      a weak agonist at the galanin receptors in these two systems. M40 acts as a weak
      antagonist of galanin in the spinal flexor reflex model. These results suggest
      that at least two subtypes of the galanin receptor may exist. Hypothalamic and
      hippocampal galanin receptors represent a putative central galanin-receptor
      subtype (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor
      may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak
      agonist. The galanin receptors in the spinal cord occupy an intermediate position
      between these two putative subtypes.

PMID- 7504302
TI  - Nitric oxide synthase in the rat anterior pituitary gland and the role of nitric
      oxide in regulation of luteinizing hormone secretion.
AB  - By using immunohistochemistry and in situ hybridization, we have demonstrated
      that the nitric oxide (NO)-synthesizing enzyme NO synthase is present in
      gonadotrophs and in folliculo-stellate cells of the anterior pituitary gland of
      male and female rats. A marked increase in levels of NO synthase protein and mRNA
      was observed after gonadectomy. In vitro studies on dispersed anterior pituitary
      cells suggest that NO inhibits gonadotropin-releasing-hormone-stimulated
      luteinizing hormone release. An inhibitory effect of NO has also been shown on
      growth-hormone-releasing-hormone-stimulated release of growth hormone [Kato, M.
      (1992) Endocrinology 131, 2133-2138]. Thus these findings support a dual
      mechanism for NO in the control of anterior pituitary hormone secretion, an
      autocrine mediation of luteinizing hormone release on gonadotrophs, and a
      paracrine effect on growth hormone secretion involving folliculo-stellate cells
      closely related to somatotrophs. We speculate that NO may participate in
      producing the pulsatile secretion patterns of these two pituitary hormones.

PMID- 7504303
TI  - Association and phosphorylation-dependent dissociation of proteins in the insulin
      receptor complex.
AB  - Receptor tyrosine kinases have been found to interact with a variety of specific
      signaling molecules. To detect molecules that interact with the insulin receptor,
      we have produced a modified insulin receptor with an additional epitope allowing
      rapid purification under mild conditions of the insulin receptor complex. By this
      method we have found multiple proteins (including the p85 subunit of
      phosphatidylinositol 3'-kinase and the ras GTPase-activating protein) that
      specifically associate with the activated (phosphorylated) insulin receptor
      (insulin receptor complex proteins) but are released from the complex after they
      are phosphorylated on tyrosine residues. We have also shown that tyrosine
      phosphorylation of p85 by the activated insulin receptor blocks binding to the
      activated receptor. These results suggest that association of proteins with the
      insulin receptor complex is controlled by phosphorylation of the receptor, while
      dissociation of insulin receptor complex proteins is controlled in turn by
      phosphorylation of the proteins in the insulin receptor complex. This process
      results in the dispersion of phosphorylated insulin receptor complex proteins
      into the cell.

PMID- 7504304
TI  - Anti-pig IgM antibodies in human serum react predominantly with Gal(alpha 1-3)Gal
      epitopes.
AB  - A major problem with pig-to-human-tissue xenograft studies is that humans have
      natural antibodies to pig cells; these antibodies would cause hyperacute
      rejection if pig tissues were xenografted to humans. Here we show that most of
      human IgM antibodies present in the serum of healthy donors and reactive with pig
      cells react with galactose in an (alpha 1-3) linkage with galactose--i.e.,
      Gal(alpha 1-3)Gal. Absorption studies demonstrated that the antibodies detected
      the same or similar epitopes on the surface of pig erythrocytes, blood and
      splenic lymphocytes, and aortic endothelial cells (EC). The antibodies were
      sensitive to 2-mercaptoethanol (2ME) treatment, did not bind to protein A or G,
      and were present in the high molecular weight fraction of serum; they are clearly
      IgM antibodies. Further, the antibodies did not react with human ABO blood group
      substances and are not related to human blood group A or B, which carry a
      terminal galactose. The reaction of human serum with pig erythrocytes was
      specifically inhibited by mono- and disaccharides: D-galactose, melibiose,
      stachyose, methyl-alpha-D-galactopyranoside, and D-galactosamine but not by D
      glucose or methyl-beta-D-galactopyranoside; demonstrating that the reaction is
      with galactose in an alpha and not a beta linkage. A cDNA clone encoding the
      murine alpha-1,3-galactosyltransferase (which transfers a terminal galactose
      residue with an (alpha 1-3) linkage to a subterminal galactose) was isolated by
      polymerase chain reaction (PCR), cloned, and transfected into COS cells, which
      are of Old World monkey origin and, like humans, do not express Gal(alpha 1
      3)Gal. After transfection, COS cells became strongly reactive with human serum
      and with IB4 lectin [which reacts only with Gal(alpha 1-3)Gal]; this reactivity
      could be removed by absorption with pig erythrocytes. As most of the antibody
      reacting with pig cells can be removed by absorption with either melibiose or
      Gal(alpha 1-3)Gal+ COS cells, most of these react with Gal(alpha 1-3)Gal. These
      findings provide the basis for genetic manipulation of the pig alpha-1,3
      galactosyltransferase for future transplantation studies.

PMID- 7504306
TI  - Muscarinic receptors--characterization, coupling and function.
AB  - At least five muscarinic receptor genes have been cloned and expressed.
      Muscarinic receptors act via activation of G proteins: m1, m3 and m5 muscarinic
      receptors couple to stimulate phospholipase C, while m2 and m4 muscarinic
      receptors inhibit adenylyl cyclase. This review describes the localization,
      pharmacology and function of the five muscarinic receptor subtypes. The actions
      of muscarinic receptors on the heart, smooth muscle, glands and on neurons (both
      presynaptic and postsynaptic) in the autonomic nervous system and the central
      nervous system are analyzed in terms of subtypes, biochemical mechanisms and
      effects on ion channels, including K+ channels and Ca2+ channels.

PMID- 7504307
TI  - Synthesis and photobiological properties of 4-hydroxymethyl-4'-methylpsoralen
      derivatives.
AB  - The synthesis and the photobiological activity of two new hydroxymethyl
      derivatives of psoralen namely 4-hydroxymethyl-4'-methyl- and 4-hydroxymethyl-4'
      methyl-8-methoxypsoralen are described. Both compounds exhibited efficient
      photobinding to DNA and RNA. The DNA-photobinding process was investigated using
      different nucleic acid structures such as double-helical DNA, ribosomal RNA,
      bacterial DNA and DNA organized in the nucleosomal arrangement. The test
      derivatives were able to induce cross-links to a similar extent as 8
      methoxypsoralen (8-MOP), used as a reference photochemotherapeutic drug. In
      contrast to 8-MOP, they produced relatively high levels of 1O2. Most
      photobiological effects (DNA synthesis inhibition, T2 phage sensitization,
      inhibition of tumor transmitting capacity) showed a good correlation with the
      extent of covalent photoaddition. On the other hand, the new 4
      hydroxymethylpsoralens were unable to induce skin erythema, in striking contrast
      with 8-MOP. Thus, neither cross-linking of the nucleic acid nor 1O2 production
      were coupled with skin phototoxicity in this class of compounds. The new
      derivatives appear to represent an important beginning to development of new
      active photochemotherapeutic agents devoid of undesired phototoxic side effects.

PMID- 7504305
TI  - Cloning, characterization, and expression of a cDNA encoding an inducible nitric
      oxide synthase from the human chondrocyte.
AB  - Incubation of human articular chondrocytes with interleukin 1 beta results in the
      time-dependent expression of nitric oxide (NO) synthase. We report here the
      isolation of a cDNA clone which encodes a protein of 1153 amino acids with a
      molecular mass of 131,213 Da and a calculated isoelectric point of 7.9. CHO cells
      transfected with a plasmid harboring this cDNA clone expressed NO synthase
      activity that was inhibited by some L-arginine analogues. The deduced amino acid
      sequence of the human chondrocyte inducible NO synthase shows 51% identity and
      68% similarity with the endothelial NO synthase and 54% identity and 70%
      similarity with the neuronal NO synthase. The similarity (88%) between the human
      chondrocyte NO synthase cDNA sequence and that reported for the murine macrophage
      suggests that the inducible class of enzyme is conserved between different cell
      types and across species.

PMID- 7504308
TI  - Microinjection of galanin into the medial preoptic nucleus facilitates copulatory
      behavior in the male rat.
AB  - The medial preoptic area (MPOA) is an important region for masculine sexual
      behavior. Because galanin (GAL) immunoreactive cells within the MPOA are affected
      by the gonadal steroid environment and GAL binding is apparent, GAL was
      microinjected site specifically in 0, 10, 50, 100, and 500 ng doses in order to
      determine effects on copulatory behavior. Unilateral microinjection of GAL within
      the medial preoptic nucleus facilitated copulatory behavior in a dose-responsive
      fashion, evidenced by an increase in the percentage of males that displayed
      sexual behaviors and a decrease in mount and intromission latencies. These
      effects required the presence of gonadal steroids, and were not due to general
      arousal as measured in open field testing. The techniques of survival analysis
      were used to display data and for statistical analysis of intromission and mount
      latencies; these approaches revealed significant effects that were not evident
      with more commonly used procedures. The results support the suggestion that
      sexually dimorphic galaninergic cell groups within the MPOA are involved in
      gonadal steroid-induced masculine sexual behavior.

PMID- 7504311
TI  - Postsynaptic actions of acetylcholine: the coupling of muscarinic receptor
      subtypes to neuronal ion channels.

PMID- 7504309
TI  - An ionizing radiation-sensitive mutant of CHO cells: irs-20. I. Isolation and
      initial characterization.
AB  - We have isolated a stable mutant of CHO cells, designated irs-20, that is
      hypersensitive to ionizing radiation. The selection system was designed to select
      for mutants unable to proliferate at the low dose rate of 0.06 Gy per hour, a
      dose rate that has little influence on the effect of radiation on the cell cycle
      of wild-type cells during 1- to 2-week exposures. The irs-20 mutant cells
      irradiated continuously at 0.06 Gy/h showed a cell cycle redistribution, with an
      increasing G2 + M-phase fraction, but underwent approximately four doublings
      before cell population growth was completely inhibited. Dose rates three to four
      times higher were required to produce similar perturbation in the cell cycle of
      wild-type cells. Asynchronous log-phase irs-20 cells were approximately twofold
      more sensitive than the parental CHO cells as measured by comparing the doses
      required to reduce survival to 10%. The survival response of synchronized irs-20
      cells after a single radiation dose of 3.8 Gy at different times during the cell
      cycle was qualitatively similar to the pattern for wild-type CHO cells for an
      approximately isosurvival dose of 7.4 Gy. The irs-20 cells were hypersensitive to
      the "radiomimetic" drug bleomycin but showed the wild-type sensitivity to ethyl
      methane sulfonate, ultraviolet light (254 nm) and mitomycin C. The irs-20 mutant
      cell has maintained its phenotype for over 1 year in continuous culture,
      indicating that the defect is genetically stable. The karyotype of the mutant
      cells is not different from that of its parent. Further evidence of stability is
      that clonal lines derived from cells surviving high radiation doses also had the
      irs-20 phenotype, and treatments with 5-azacytidine sufficient to cause high
      reversion (approximately 2 x 10(-1)) to proline independence resulted in no
      measurable reversion to wild-type radiosensitivity.

PMID- 7504310
TI  - Evolution and acetylcholine receptors.

PMID- 7504312
TI  - Muscarinic receptor subtype-specific coupling to second messengers in neuronal
      systems.

PMID- 7504314
TI  - Cross-reactive antigenic domains of the flagellin protein of Borrelia
      burgdorferi.
AB  - The p41 flagellin of Borrelia burgdorferi is the most common antigen recognized
      by serum of patients with Lyme borreliosis. This antigen shares amino acid
      homology, particularly in the amino and carboxy termini, with periflagellar
      antigens found in other microorganisms including Treponema pallidum. We cloned
      and expressed the p41 open reading frame in Escherichia coli and expressed it
      both as TrpE fusion and full-length unfused proteins. Also, we generated deletion
      constructs of various portions of the gene. Sera from patients with late Lyme
      borreliosis and secondary syphilis were used to identify the recombinant proteins
      by immunoblot analysis. Sera from 26 patients with Lyme borreliosis, 20 with
      secondary syphilis and 10 controls were used to identify cross-reactive domains
      of the B. burgdorferi flagellin. The variable region (amino acids 131-234) of the
      protein was recognized by 59% (15/26) of patients with late Lyme borreliosis
      compared to 30% (6/20) of patients with secondary syphilis and no (0/10) control
      patients. It appears that cross-reactive epitopes between B. burgdorferi and T.
      pallidum extend to the variable region of the flagellin.

PMID- 7504313
TI  - [Pharmacological properties of aprotinin and its therapeutic use in heart
      surgery].
AB  - Aprotinin (Trasylol) is a protease-specific inhibitor that has been used for over
      5 years in extracorporeal circulation (ECC) during cardiac surgery. Patients
      treated with this inhibitor have considerably less postoperative bleeding, along
      with correspondingly lower consumption of blood products. This article reviews
      the history of the drug, its pharmacokinetics and pharmacodynamics, its
      usefulness in biological sciences and its clinical application in cardiac
      surgery, as well as drug interactions and side effects.

PMID- 7504315
TI  - Construction and first characterization of two reciprocal hybrids between LamB
      from Escherichia coli K12 and Klebsiella pneumoniae.
AB  - The LamB proteins from Klebsiella pneumoniae and Escherichia coli K12 were
      previously shown to be highly homologous. The most conserved parts correspond to
      the N-proximal third and to the transmembranous portions of the molecule, while
      the variability occurred essentially within regions exposed to the cell surface
      or to the periplasm. Since the two proteins displayed identical in vitro trimer
      stability and in vivo pore properties, we tested whether the N-terminal parts of
      the two proteins could be exchanged and still allow the formation of stable and
      functional maltoporins. For that purpose, we expressed the LamB protein from K.
      pneumoniae in E. coli K12, and constructed two reciprocal hybrids between LamB
      from E. coli K12 and LamB from K. pneumoniae. The first hybrid (LamBE.c.-K.p.) is
      composed of residues 1 to 183 from LamBE.c. followed by residues 184 to 404 from
      LamBK.p. The second one comprises residues 1 to 183 from LamBK.p., followed by
      residues 184 to 421 from LamBE.c. (LamBK.p.-E.c.). Both hybrid proteins were
      correctly incorporated in the outer membrane of E. coli K12. Like the two
      parental LamB proteins, the two hybrids could be purified by affinity
      chromatography on a starch-sepharose column. The LamBE.c.-K.p. hybrid formed
      highly stable trimers, but was strongly impaired in its in vivo maltose transport
      function (15% of the wild-type level). The trimers formed by LamBK.p.-E.c. hybrid
      were less stable, but could be detected on the surface of intact cells by four
      anti-LamBE.c. monoclonal antibodies. This hybrid was also affected in its in vivo
      maltose transport function (30% of the wild-type level). As expected from the
      location of the residues critical for phage adsorption, both proteins had lost
      the phage receptor activity of the E. coli K12 LamB protein. We also examined
      whether LamBE.c. could form heterotrimers with LamBK.p., LamBK.p.-E.c., and
      LamBE.c.-K.p. In no case were heterotrimers detected, indicating that both
      terminal parts of the LamB protein are involved in homotrimer formation. All
      these data suggest that trimer formation and activity involve rare variable
      residues in the conserved regions and/or variable regions.

PMID- 7504316
TI  - Identification of a Clostridium cocleatum strain involved in an anti-Clostridium
      difficile barrier effect and determination of its mucin-degrading enzymes.
AB  - We isolated Gram-positive circular bacterium HB1 from intestinal microflora
      showing resistance to colonization by Clostridium difficile in mice (Su et. al.,
      1986a,b). We studied its enzymatic capacity to degrade mucin the first potential
      barrier to implantation of strains in the intestine. Its biochemical
      characteristics, terminal metabolites and the electrophoretic profiles of
      proteins and DNA-DNA homology indicated that it was a strain of Clostridium
      cocleatum. This strain displayed numerous glucosidase activities which were
      assumed to play a role in the degradation of mucin oligosaccharide chains in the
      digestive tract. These enzymes included alpha- and beta-galactosidases, beta
      glucosidase, beta-N-acetylglucosaminidase, sialidase and alpha-N
      acetylgalactosaminidase.

PMID- 7504318
TI  - Palliative treatment of neuroendocrine tumors.
AB  - Effective palliation of patients with incurable neuroendocrine tumors requires
      both control of hormonal overproduction symptoms as well as control of tumor
      growth. Several important advances have been made in recent years toward these
      two goals. Octreotide and omeprazole have both been extremely effective in
      ameliorating hormonal symptoms of carcinoids, islet cell tumors and medullary
      thyroid carcinoma. Newer cytotoxic chemotherapy regimens and interferon have
      increased response rates over traditional therapy. More aggressive surgical
      extirpation of metastatic disease has also been beneficial.

PMID- 7504317
TI  - [Significance of endogenous nitric oxide production for the effect of nitrates
      and in septic shock].
AB  - The endothelial relaxation factor postulated by Furchgott has been identified as
      the endogenous nitro-vasodilatator nitric oxide (nitrogen monoxide, NO). NO is
      derived from L-arginine and plays an important role in the regulation of
      circulation. In man, too, inhibitors of NO synthesis like L-NG monomethylarginine
      (L-NMMA) led to hypertension as well as to reduction of local blood flow. In vivo
      inhibition of NO synthesis leads to amplification of the effect and of the
      duration of the effect of nitrates. L-arginine/NO metabolism has also been
      detected in nonvascular tissues, i.e. from lungs, gastrointestinal tract and
      urogenital tract. The discovery of inducible nitric-oxide synthase activity in
      vascular smooth muscle cells, able to produce a great amount of NO, represents
      another important recent development. Important stimuli for the induction of this
      NO-synthase are cytokines that play possibly an important clinical role in the
      context of endotoxemic shock. Research over the last ten years has demonstrated
      that the L-arginine/NO system represents a central biological regulatory
      mechanism that plays an important role under physiologic and pathophysiologic
      conditions not only for the circulation but also in other organs.

PMID- 7504319
TI  - [The treatment of pain. 3. Cancer pain and palliative care].

PMID- 7504321
TI  - Hepatitis C virus infection with progression to hepatocellular carcinoma: a
      report of five prospectively followed patients in Sweden.
AB  - Five Swedish patients with chronic hepatitis C were prospectively followed until
      hepatocellular carcinoma (HCC) developed. Hepatitis C virus (HCV) antibodies were
      analysed by a second generation anti-HCV ELISA and a recombinant immunoblot assay
      (RIBA-2) and viraemia by detection of serum HCV RNA by polymerase chain reaction.
      Four patients had post transfusion hepatitis and in one patient the source of
      infection was unknown. HCC developed after 8 to 23 years of mostly asymptomatic
      disease and all patients died. Four of them were repeatedly biopsied during
      follow-up and all had chronic active hepatitis. When HCC was diagnosed, cirrhosis
      was present in all 5. In 4 patients with available sera, anti-HCV was positive
      and confirmed with RIBA-2, whereof 2 were reactive only to the c-22 and c-33c
      epitopes. HCV-RNA was present in all sera when HCC was diagnosed. Thus, after
      prolonged disease duration these patients were still viraemic.

PMID- 7504320
TI  - Presence of mast cells in various oral mucosal sites in juvenile and adult rats.
AB  - The present investigation was designed to study the number of mast cells in
      various oral mucosal sites in juvenile and adult rats, with special reference to
      presence of subtypes of mast cells. Fifteen juvenile (1-month-old) and 15 adult
      (6-month-old) rats were used. Biopsies were taken from tongue, bucca, marginal
      gingiva (incisor area), and intestine (jejunum). For optimal preservation of the
      stainability of subtypes of mast cells, a fixative with low aldehyde
      concentration and low pH was used. The biopsies were embedded in paraffin-wax.
      The first of three consecutive sections (5 mu) was stained in toluidine blue for
      30 s, the second in toluidine blue for 7 days, and the third in astra
      blue/safranine. The total number of mast cells was represented by all cells
      positive to toluidine blue after 7 days' staining, or the sum of cells positive
      to astra blue and safranine. Cells positive to toluidine blue after 30 s were
      classified as connective tissue mast cells (CTMCs), and those positive after 7
      days, but not after 30 s, as mucosal mast cells (MMCs). Cells positive to
      safranine in the astra blue/safranine staining sequence were classified as CTMCs,
      and those positive to astra blue as MMCs. Cells with intermediate staining
      characteristics in the astra blue/safranine staining sequence were recorded
      separately. The total number of mast cells in the tongue, buccal mucosa, and
      gingival mucosa was significantly higher in the juvenile than in the adult rats.
      In the buccal and gingival mucosa, more than twice as many mast cells were found
      in the young animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504323
TI  - Closing in on SH2 specificity.

PMID- 7504322
TI  - Analysis of CD36 binding domains: ligand specificity controlled by
      dephosphorylation of an ectodomain.
AB  - The protein CD36 is a membrane receptor for thrombospondin (TSP), malaria
      infected erythrocytes, and collagen. Three functional sequences were identified
      within a single disulfide loop of CD36: one that mediates TSP binding (amino
      acids 87 to 99) and two that support malarial cytoadhesion (amino acids 8 to 21
      and 97 to 110). One of these peptides (p87-99) is a consensus protein kinase C
      (PKC) phosphorylation site. Dephosphorylation of constitutively phosphorylated
      CD36 in resting platelets and a megakaryocytic cell line led to the loss of
      collagen adhesion and platelet reactivity to collagen, with a reciprocal increase
      in TSP binding. PKC-mediated phosphorylation of this ectodomain resulted in a
      loss of TSP binding and the reciprocal acquisition of collagen binding. In site
      directed mutagenesis studies, when the threonine phosphorylation site was changed
      to alanine, CD36 was expressed in a dephosphorylated state and bound to TSP
      constitutively.

PMID- 7504324
TI  - Activation of exocytosis by the heterotrimeric G protein Gi3.
AB  - Secretagogues of rat peritoneal mast cells, such as mastoparan and compound
      48/80, induce mast cell exocytosis by activating directly the guanosine
      triphosphate-binding proteins that are required for exocytosis. The introduction
      of a synthetic peptide that corresponds to the carboxyl-terminal end sequence of
      G alpha i3 into the cells specifically blocked this secretion. Similar results
      were obtained when antibodies to this peptide were introduced. The G alpha i3 was
      located in both the Golgi and the plasma membrane, but only the latter source of
      G alpha i3 appeared to be essential for secretion. These results indicate that G
      alpha i3 functions to control regulated exocytosis in mast cells.

PMID- 7504325
TI  - Characterization of a pathway for ciliary neurotrophic factor signaling to the
      nucleus.
AB  - Components of a signaling pathway that couples the ciliary neurotrophic factor
      (CNTF) receptor to induction of transcription were identified. CNTF stimulated
      the tyrosine phosphorylation of p91, a protein implicated in interferon signaling
      pathways, and of two proteins that are distinct but related to p91. Tyrosine
      phosphorylated p91 translocated to the nucleus, where p91 and p91-related
      proteins bound to a DNA sequence found in promoters of genes responsive to CNTF.
      This DNA sequence, when inserted upstream of a reporter gene, conferred a
      transcriptional response to CNTF. A pathway that transduces interferon signals
      may therefore have a more general function in the propagation of responses to
      certain neurotrophic factors.

PMID- 7504326
TI  - Hyperthermia--its actual role in radiation oncology. Part II: Clinical
      fundamentals and results in superficial tumors.
AB  - This overview summarizes the most important clinical fundamentals to implement
      combined hyperthermia (HT) and radiotherapy (RT) in clinical trials and reviews
      clinical HT-RT data obtained in superficial and medium depth tumors treated with
      external heating devices. In the first part we discuss the following clinical
      fundamentals: selection of appropriate clinical sites for HT-RT studies,
      selection of suitable HT-devices, principle design of clinical HT-RT studies,
      requirements for treatment prescription, relevant treatment endpoints, definition
      and assessment of a thermal enhancement ratio (TER) and therapeutic gain factor
      (TGF), impact of prognostic parameters on treatment stratification and
      statistical evaluation. In the second part we review and discuss clinical results
      of thermoradiotherapy (HT-RT) for advanced breast carcinoma, recurrent breast
      cancer, advanced head and neck tumors, cervical neck node metastases, malignant
      melanomas and residual microscopic disease. In addition, clinical results of
      pilot studies are reviewed, which have applied a triple modality approach of
      thermo-radiochemotherapy (HRC) for various tumors. Finally, possible future
      perspectives of clinical HT-RT research are outlined.

PMID- 7504327
TI  - A human monoclonal antibody, produced following in vitro immunization,
      recognizing an epitope shared by HLA-A2 subtypes and HLA-A28.
AB  - In vitro immunization and subsequent immortalization of peripheral blood cells of
      a multiparous woman has resulted in the production of a stable human mouse
      heterohybridoma, 5C2A2, secreting an HLA-A2/A28-specific human monoclonal
      antibody. Although possibly exposed to HLA-A2 by transfusions, the cell donor
      showed no HLA-A2-specific serum antibodies. The present protocol for in vitro
      immunization includes the elimination of suppressor cells from the responder cell
      population, the presence of irradiated allogeneic lymphocytes as a source of
      antigen, as well as stimuli--recombinant interleukin-2 and a B-cell specific
      nucleoside analogue--causing the proliferation of B lymphocytes, prior to
      immortalization. The ability of the antibody 5C2A2 to detect all known HLA-A2
      subtypes, except A2.3, and A28, allows identification of the serological epitope
      on the HLA-A2 molecule. Application of this in vitro immunization method allows
      the production of a set of HLA monoclonal antibody-secreting human hybridomas,
      independent of the existence of serum HLA antibodies in the lymphocyte donors.

PMID- 7504328
TI  - Summary report from the first international workshop on soluble HLA antigens.
      Paris, August 1992.
AB  - The First International Workshop on Soluble HLA antigens focused on the
      comparison of immunoassay procedures for quantitation of soluble HLA (sHLA) class
      I antigens and the selection of a sHLA class I antigen international standard.
      Several sets of serum, plasma, and cell culture supernatant specimens were
      assayed blindly for levels of sHLA class I antigens by 15 participating
      laboratories using different immunoassay formats. The sandwich ELISA using (i)
      for antigen capture: an anti-HLA class I heavy chain monoclonal antibody (mAb)
      specific for a monomorphic epitope, and (ii) for antigen detection: an anti-beta
      2 microglobulin antibody-enzyme conjugate, was the assay format of choice. There
      was a high inter-laboratory correlation among the majority of laboratories. All
      serum and plasma specimens from normal donors, and from a single transplant
      patient, had detectable levels of sHLA class I antigens. Paired serum and plasma
      specimens had similar levels of sHLA class I antigens, although plasma sHLA
      antigens seemed more stable than serum sHLA antigens. sHLA-A2 and sHLA-B7
      antigens were detected in all specimens from HLA-A2 and HLA-B7 donors,
      respectively, using allele-specific ELISAs. No difference in reactivity was
      observed for quantitation of native sHLA class I antigens whether the capture mAb
      was TP25.99 (alpha 3 domain-specific) or W6/32 (alpha 2 + alpha 3-specific).
      However, a human-mouse chimeric sHLA class I antigen reacted weakly in assays
      which used TP25.99 mAb. The wide variation among laboratories in their reporting
      of micrograms/ml units pointed to the need for an inter-laboratory
      standardization based on a calibrated sHLA antigen preparation. T.sB7, an sHLA-B7
      antigen derived from a cell line transfected within human beta 2 microglobulin
      and HLA-B7 genes, was accepted as the First sHLA class I Antigen International
      Standard at the workshop meeting.

PMID- 7504329
TI  - Multiple myeloma occurring in early stage primary biliary cirrhosis.
AB  - B-cell neoplasms are not infrequently associated with autoimmune diseases. A 60
      year-old man with multiple myeloma developing in an early stage primary biliary
      cirrhosis was reported. Initially, he had hypergammaglobulinemia with monoclonal
      gammopathy (IgG-kappa type), elevation of serum IgG and IgM, and positive serum
      antimitochondrial antibodies. There were compression fractures of the lumbar
      vertebrae, where bone marrow aspiration revealed proliferating myeloma cells.
      Liver biopsy revealed destruction of bile duct surrounded by an inflammatory
      infiltrate, which was consistent with stage I primary biliary cirrhosis. The
      association suggested the role of immunoregulatory abnormalities in the
      development of multiple myeloma.

PMID- 7504330
TI  - Effects of Percoll discontinuous density gradients vs SpermPrep II vs Sephadex G
      50 gel filtration on semen parameters.
AB  - There are various methods of separating sperm from seminal plasma for subsequent
      intrauterine insemination (IUI) and for in vitro fertilization (IVF). The purpose
      of the present study was to assess and compare semen parameters following
      Sephadex, Percoll and SpermPrep II separation techniques. The SpermPrep II is
      also a Sephadex preparation but uses a different bead size, less Sephadex and is
      a quicker method. The specimens (n = 16) were initially evaluated for count, (C;
      x 10(6)/ml)% motility (MO), grade of motility (GR; %), and HOS test scores. Each
      specimen was then divided into 3 equal aliquots and prepared as follows: 1)
      layered onto a modified Percoll discontinuous density gradient column; 2)
      processed using SpermPrep II; and 3) filtered through a Sephadex gel filtration
      column (G-50). The results show all 3 treatments yielded lower (p < 0.01) counts
      as compared to control values but no differences were noted among them. Percoll
      and SpermPrep II increased MO (p < 0.01) where Sephadex reduced it (p = NS).
      Percoll and SpermPrep II improved the % of best quality sperm but not Sephadex
      with SpermPrep II being higher than Percoll. There were increases (p < 0.05) in
      HOS values in all experimental treatments with SpermPrep II being the best.
      However, this study did not show as many males with HOS scores below 50% as noted
      in other studies. Finally, Percoll and SpermPrep II seem equally effective
      methods for producing high quality sperm for IUI or IVF although SpermPrep II is
      quite faster.

PMID- 7504331
TI  - Changes in pulmonary hemodynamics during normoxia and hypoxia in awake rats
      treated with intratracheal bleomycin.
AB  - Pulmonary hemodynamics of bleomycin-induced interstitial fibrosis model (group
      BLM, n = 10) and saline-treated control (group-C, n = 12) were studied in awake
      rats. Four weeks before hemodynamic study, bleomycin sulfate and normal saline
      was intratracheally instilled to the group-BLM and the group-C, respectively.
      Pulmonary artery and abdominal aortic catheters were indwelled two days before
      the hemodynamic study. In room air, mean pulmonary artery pressure (Ppa) was
      significantly higher and systemic artery pressure was significantly lower in
      group-BLM than in group-C; Ppa = 21 +/- 1 cmH2O (mean +/- S.E.) for group-C and
      38 +/- 4 cmH2O for group-BLM. Cardiac output did not differ among the groups.
      Mean pulmonary vascular resistance (PVR) of group-BLM was double that of group-C.
      Right ventricle was hypertrophic in group-BLM. When exposed to 10% O2, PVR of
      group-C significantly rose, whereas PVR of group-BLM showed very little increase,
      showing attenuation of the hypoxic pulmonary vasoconstriction (HPV). Magnitude of
      the HPV was inversely related to Ppa during air breathing. We conclude that
      notable pulmonary hypertension and right ventricular hypertrophy occur, and HPV
      is blunted four weeks after bleomycin instillation, at the most severe period of
      this lung fibrosis model. We speculate that the high intravascular pressure
      partly contributed to the blunted HPV in bleomycin-treated group.

PMID- 7504332
TI  - Reinforcing aerosol cisplatin for radiotherapy of laryngeal cancer.
AB  - To attain its increased tumor concentration and to avert its systemic adverse
      effects, aerosol cisplatin (CDDP) was incorporated into radiotherapy (RT) of
      laryngeal cancer. Nine patients were asked to inhale the aerosol following each
      RT session. Their clinical tumor response was favorable, and histopathologic
      survey in selected cases revealed elimination of viable cancer cells. However
      limited, there have been no reports of cancer recurrence yet. This reinforcing
      plan of aerosol CDDP for RT bleomycin would certainly offer a better way of
      treating laryngeal cancer, and probably those malignancies facing the
      nasopharyngobronchial airway as well.

PMID- 7504333
TI  - The production of granulocyte colony-stimulating factor and interleukin 6 by
      human bone marrow stromal cells in aplastic anemia.
AB  - Stromal cells are known to produce granulocyte colony-stimulating factor (G-CSF)
      and interleukin 6 (IL-6). To assess the function of bone marrow stromal cells in
      the pathological state, we studied their in vitro ability to produce G-CSF and IL
      6 in 9 patients with aplastic anemia and 5 normal volunteers, using an enzyme
      immunoassay method. Constitutive production of IL-6, but not G-CSF, was detected
      in almost all cases. Interestingly, the inducible production of G-CSF and IL-6 by
      stromal cells after stimulation with interleukin-1 and/or lipopolysaccharides was
      severely depressed in 3 patients with aplastic anemia. Our results may reflect
      poor hematopoietic activity in the bone marrow in some cases of aplastic anemia.

PMID- 7504334
TI  - A review of the relationship between acute toxicity (LC50) of gamma
      hexachlorocyclohexane (gamma-HCH, Lindane) and total lipid content of different
      fish species.
AB  - This paper provides an explanation for a 40-fold difference in the acute toxicity
      (LC50) of gamma-hexachlorocyclohexane (gamma-HCH, Lindane) in 14 different fish
      species, based on well recognized principles of toxicokinetics and toxicodynamics
      in combination with a compilation of data from the literature and some original
      data. The 48-h median lethal concentration (48-h LC50) of gamma-HCH in 14 fish
      species, belonging to 6 families, range from 22 to 900 micrograms/l. A
      significant positive linear relationship was found between lipid content (% of
      wet weight) and the 48-h LC50 of gamma-HCH in these fish species, revealing that
      the toxicity of gamma-HCH in various fish species is decreasing with increasing
      total lipid content. If median lethal concentrations are normalized for 1% lipid
      content, then the range of 48-h LC50s is reduced to between 18 and 32
      micrograms/l. It is concluded that lipids of aquatic organisms can serve (among
      other functions) as a protective storage site against the toxic effects of gamma
      HCH and, possibly, of other lipophilic, persistent organic chemicals which are
      bioconcentrated in body lipids. Therefore, in organisms with higher lipid
      content, a smaller fraction of a lipophilic chemical will reach target organs
      (liver, lung, central and peripheral nerves, etc.) to cause adverse effects.
      Results suggest that this correlation can be used to extrapolate the acute
      toxicity (48-h LC50) of gamma-HCH to other fish species if their lipid content is
      known. Furthermore, the data generated by extrapolation of this correlation could
      be useful in the environmental risk assessment of freshwater and marine
      organisms.

PMID- 7504336
TI  - The effect of nitric oxide synthase inhibition on infarct volume after reversible
      focal cerebral ischemia in conscious rats.
AB  - BACKGROUND AND PURPOSE: Previous in vitro and in vivo studies of the effects of
      nitric oxide synthase inhibition in the central nervous system have yielded
      conflicting results concerning the role of nitric oxide in the events that lead
      to ischemic injury. In this study, we tested the hypothesis that preischemic
      inhibition of nitric oxide synthase increases infarct volume after reversible
      focal cerebral ischemia in rats. METHODS: NG-nitro-L-arginine methyl ester
      hydrochloride 15 mg/kg IV or an equivalent volume of saline was administered to
      adult Wistar rats 15 minutes before middle cerebral artery occlusion by the
      intraluminal suture method. After 2 hours of ischemia, the suture was withdrawn,
      and rats were allowed to survive for 3 days. Areas of infarction in 10
      hematoxylin-eosin-stained sections were measured and used to determine infarct
      volume. RESULTS: Administration of NG-nitro-L-arginine methyl ester hydrochloride
      increased hemispheric infarct volume by 137% over control (60.9 +/- 30.5 to 144.3
      +/- 19.6 mm3, P < .05; mean +/- SEM). Cortical and subcortical infarct volumes
      were increased by 176% (33.8 +/- 21.9 to 93.3 +/- 15.2 mm3, P < .05) and 103%
      (25.1 +/- 9.4 to 51.0 +/- 5.5 mm3, P < .03), respectively. CONCLUSIONS: Nitric
      oxide synthase inhibition increases infarct volume and decreases the variability
      of the response to middle cerebral artery occlusion in Wistar rats, a strain that
      is normally resistant to focal cerebral ischemic injury owing to extensive
      collateralization. The mechanism of the deleterious effect of nitric oxide
      synthase inhibition likely involves a more severe degree of blood flow reduction
      during and after middle cerebral artery occlusion, primarily by preventing the
      vasodilatory response of collateral vessels to proximal middle cerebral artery
      occlusion. Maintenance of nitric oxide synthase activity during and after focal
      cerebral ischemia appears to minimize ischemic injury.

PMID- 7504337
TI  - The pharmacology of AMPA receptors and their antagonists.

PMID- 7504335
TI  - Cerebral endothelial nitric oxide synthase expression after focal cerebral
      ischemia in rats.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to measure the temporal
      profile of expression of the endothelial nitric oxide synthase (NOS) in cerebral
      microvessels after middle cerebral artery occlusion in the rat. METHODS: Middle
      cerebral artery occlusion was performed on 24 male Wistar rats by extracranial
      insertion of a 4-0 nylon monofilament into the internal artery. Three additional
      rats were used as controls. Animals were killed at 1, 2, 4, 6, 24, 48, 72, and
      168 hours after middle cerebral artery occlusion (n = 3 per time point). Rat
      brains were perfused with buffer, frozen, sectioned, and stained with a
      monoclonal antibody against endothelial NOS. Adjacent sections were stained with
      hematoxylin and eosin for evaluation of neuronal damage. RESULTS: The endothelial
      NOS in the cerebral vessels was upregulated at 1 hour after induction of ischemia
      throughout the ischemic region. The induction of the endothelial NOS
      progressively increased up to 24 hours of ischemia. In the periphery of the area
      of necrosis in the cortex, a delayed (24-hour) upregulation of the endothelial
      NOS remained constant throughout the duration of ischemia. CONCLUSIONS: The rapid
      and intense differential expression of the endothelial NOS in the core and
      peripheral areas of the lesion indicates a role for endothelial NOS in ischemic
      cell damage and suggests that the increased expression of NOS may mediate changes
      in the cerebral blood flow.

PMID- 7504338
TI  - AMPA antagonists: do they hold more promise for clinical stroke trials than NMDA
      antagonists?
AB  - The cytoprotective effects of MK-801 and NBQX, selective N-methyl-D-aspartate
      (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
      receptor antagonists, respectively, were compared both singularly and in
      combination in models of transient severe forebrain and transient focal cerebral
      ischemia. After 10 minutes of four-vessel occlusion ischemia, the sodium salt of
      NBQX (30 mg/kg IP) given at the time of reperfusion and, subsequently, 15 and 30
      minutes later produced a dramatic reduction in CA1 hippocampal necrosis at 7
      days. This effect was not obtained with the intraperitoneal administration of
      either MK-801 (1 mg/kg x 3) or the combination of both NBQX and MK-801 given at
      the same time intervals. This effect of intraperitoneal NBQX alone was reproduced
      in a two-vessel occlusion/hypotension model using this same drug administration.
      Delayed treatment with both NBQX and GYKI 52466, but neither MK-801 nor the
      combination of NBQX and MK-801 given after a delay, produced a significant
      reduction in the mean volume of neocortical infarction after transient focal
      ischemia. We conclude that the AMPA receptor may play a more important role than
      the NMDA receptor in both selective ischemic necrosis of hippocampal neurons and
      in neocortical infarction. AMPA antagonists should be subjected to clinical
      stroke trials.

PMID- 7504339
TI  - Validation and quality assurance program for monitoring tacrolimus (FK 506)
      concentrations in plasma and whole blood.
AB  - Tacrolimus (FK 506), an investigational immunosuppressant drug, is undergoing
      several trials for various transplantations where protocols call for monitoring
      plasma and/or whole blood 12-h trough concentrations. Initially, the FK 506
      Central Laboratory (FCL) adapted an established enzyme immunoassay (EIA) for FK
      506 in plasma and provided clinical monitoring services for hepatic
      transplantation trials. Within 1 year, 16 clinical sites participating in these
      trials began direct use of the immunoassay for plasma and whole blood. A five
      step validation sequence facilitated rapid training and implementation of
      proficient assay services. All laboratories utilized common reagents, standards,
      and procedures. Participation in a quality assurance program involved monthly
      analysis of the three proficiency unknowns supplied by the FCL and reciprocal
      analysis of five patient samples (cross-checks) by the FCL. The quality of the
      data produced was assessed by proficiency scores, bivariate regression analysis,
      and correlations that demonstrated the concordance of their assay results for FK
      506 in plasma and whole blood.

PMID- 7504340
TI  - Pilot study of exposure to Pseudomonas pseudomallei in northern Vietnam.

PMID- 7504341
TI  - The association of the induction of vascular cell adhesion molecule-1 with
      cytomegalovirus antigenemia in human heart allografts.
AB  - Previous studies have suggested that during acute heart allograft rejection the
      expression of vascular adhesion molecules is induced. This study was designated
      to investigate the expression of three adhesion molecules ICAM-1 (CD 54), VCAM-1,
      and ELAM-1, and the counter-ligands LFA-1 (CD 18), Mac-1 (CD 11b/CD 18), and VLA
      4 (CD 49d) in frozen sections of endomyocardial biopsies (EMB) of heart
      allografts in relation to onset of CMV infection recorded as CMV antigenemia. The
      expression of MHC class II antigens and interleukin-2-receptor was also analyzed.
      A total of 105 EMBs and 840 immunoperoxidase stainings obtained from 21 heart
      transplant recipients were analyzed. EMBs from 9 patients with CMV infections, 5
      patients with rejections, and 7 patients with a noncomplicated postoperative
      course were included. An induction of VCAM-1 occurred in relation to onset of CMV
      antigenemia. The expression of VCAM-1 remained elevated for several weeks
      declining slowly to control levels. Associated with CMV infection, capillary
      expression of VCAM-1 (P < 0.001) and ELAM-1 (P < 0.03) was significantly induced
      when compared with control biopsies. ICAM-1 expression was always seen in
      capillaries--and also in controls. A striking difference in the expression of
      VCAM-1 during rejection and CMV infection was observed: in most rejecting
      biopsies only a few capillaries stained faintly for VCAM-1, whereas during CMV
      infection multifocal intense staining was found (P < 0.0001). Induction of ELAM-1
      was associated with acute rejections. In general, the expression of ligand
      counterparts was at a higher level during rejection compared with CMV infection.
      However, a short-term induction of VLA-4 occurred after the onset of CMV
      antigenemia (N.S.). Thus, the VCAM-1/VLA-4 ligand pair may play an important role
      in adhesion of lymphocytes and monocytes to capillary endothelium during active
      CMV infection and may also contribute to the pathogenesis of increased
      vasculopathic changes reported in CMV-infected heart transplant recipients.

PMID- 7504342
TI  - The effect of FK506 on canine bile flow.
AB  - While the primary immunosuppressive agents utilized in solid-organ
      transplantation are steroids and cyclosporine, the more recently introduced agent
      FK506 is assuming a progressively more important role as an immunosuppressant,
      particularly in liver transplantation. While the effect of cyclosporine on rat
      and canine bile flow has been well evaluated, no information is available
      regarding the effect of FK506 on bile flow. Dogs with chronic biliary fistulas
      were utilized, enabling unanesthetized animals to be studied. FK506 was
      administered intravenously in varying doses, and bile volume, bile salts, and
      bile electrolytes were measured. FK506 produced dose-related increases in bile
      volume and bile chloride concentration and output, with 8 micrograms/kg-1hr-1
      being the maximal dose. To ascertain that the response was not osmotic in
      association with FK506 secretion in bile, 500 micrograms/kg-1hr-1 FK506 was
      administered, which did not produce a choleresis significantly greater than 8
      micrograms/kg-1hr-1. FK506 was subsequently administered orally in daily dose of
      0.15 mg/kg-1 for two weeks. Oral FK506 did not consistently increase bile flow,
      as evaluated by a bile salt dose-response curve (9, 18, 36 mumol/min sodium
      taurocholate) but did significantly increase bile chloride secretion. Two weeks
      of oral administration of FK506 in therapeutic doses did not significantly alter
      serum bile salt concentrations. The results of this study indicate that
      intravenous FK506 produces a chloride-rich choleresis in dogs.

PMID- 7504344
TI  - Depletion of the helper/inducer (memory) T cell subset using a bispecific
      antibody-toxin conjugate directed against CD4 and CD29.
AB  - We have developed a bispecific antibody that recognizes the CD4 and CD29 antigens
      simultaneously and that was examined for its ability to target CD4+CD29bright T
      cells. The premise for using bispecific antibody-toxin conjugates was that
      monovalent binding to one antigen would not result in internalization while
      binding through both antigens would predispose toward endocytosis and delivery of
      the toxin to the cell interior. In this study, we show that the bispecific
      antibody binds monovalently to CD4 and CD29 and bivalently to both antigens. Both
      monovalent and bivalent binding rendered the target cells sensitive to complement
      mediated lysis, demonstrating that this effector modality cannot take advantage
      of the dual specificity of the antibody. Bivalent binding, however, allowed
      modulation of more than 60% of the bound antibody off the surface of
      CD4+CD29bright cells, which we further exploited to deliver a toxin moiety
      preferentially to CD4+CD29bright cells. Immunoconjugates incorporating blocked
      ricin (a ricin holotoxin that has its intrinsic galactose-binding sites blocked
      by chemically linked affinity ligands) preferentially killed CD4+CD29bright cells
      in vitro by a factor of 25 in comparison with killing of total CD4+ cells in
      functional assays. Assays on resting PBL demonstrated a similar specificity of
      the bispecific immunotoxin for CD4+CD29bright cells with a concomitant relative
      survival of CD4+CD29dim (CD45RA+). We demonstrated that the potency of the
      immunotoxin is not only a function of its affinity but also of its propensity to
      internalize, and that this property is influenced by the degree of bivalent
      binding. These results open up the possibility of engineering bispecific antibody
      toxin conjugates for use as therapeutic immunotoxins for selective removal of
      restricted T cell subsets.

PMID- 7504343
TI  - The expression of acidic fibroblast growth factor (heparin-binding growth factor
      1) and cytokine genes in human cardiac allografts and T cells.
AB  - The purpose of this study was to investigate the role of cytokines and growth
      factors in cardiac allograft rejection and vasculopathy (CAV). The polymerase
      chain reaction (PCR) was used to detect the expression of IL-1, IL-2, IL-4, IL-5,
      IL-6, TNF-alpha, IFN-gamma, TGF-beta, TCR-beta chain and aFGF genes in 21
      myocardial biopsies obtained from 9 heart transplant patients. There was no
      statistically significant correlation between cytokine gene expression and
      rejection, although a trend toward increased IL-6 and TGF-beta expression was
      noted with rejection (6 of 10 biopsies with vs. 1 of 7 without rejection, and 4
      of 9 biopsies with vs. none of 7 without rejection, respectively). IL-2 gene
      expression was detected in only 2 of 21 biopsies, both positive for rejection. IL
      1, IL-4, IL-5, CD8, IFN-gamma, and TNF-alpha were not detected in any of the
      biopsies. TCR-beta chain mRNA was found in all biopsies, indicating the
      invariable presence of T cells regardless of histologic diagnosis of rejection.
      The aFGF gene was expressed in the majority (18 of 21) of biopsies, and its
      presence was not correlated with rejection. In addition to mRNA for the complete
      coding sequence of aFGF, two alternatively spliced mRNAs for aFGF were present in
      myocardial biopsies. Because aFGF and TCR beta genes were expressed in most
      biopsies, we determined whether aFGF mRNA was expressed in T cells; aFGF
      transcripts were found in 2 of 5 T-cell clones examined. Thus, aFGF mRNA in
      cardiac allografts may have been induced within the myocardium or elaborated by
      infiltrating T cells. The presence of mRNA for aFGF, a potent endothelial and
      smooth muscle cell mitogen, in allograft myocardium suggests that aFGF may play a
      role in the pathogenesis of CAV.

PMID- 7504346
TI  - FK506--reversal of humorally mediated cardiac allograft rejection in the presence
      of preformed anti-class I antibody.

PMID- 7504345
TI  - T cells bind to the endothelial adhesion molecule GMP-140 (P-selectin).
AB  - A crucial step in an effective immune response is the adhesion of circulating
      lymphocytes. Lymphocytes must attach to endothelial cells before they can migrate
      into the graft. It has been shown that T cells bind to ICAM-1 and VCAM-1.
      Additionally, certain T cell subsets bind to ELAM-1. We now report that resting
      CD4+ and CD8+ T cells as well as individual CD4+ T cell clones and CD8+ T cell
      lines bind to GMP-140 in an adhesion assay using protein chimeras consisting of
      the extracellular domain of GMP-140 linked to the hinge domain of human IgG1.
      Whereas resting T cells bound similarly to ELAM-1 IgG and GMP-140 IgG, activated
      T cells represented by CD4+ T cell clones and CD8+ T cell lines bound to GMP-140
      IgG, but not to ELAM-1 IgG. Neither the binding to immobilized GMP-140 IgG, nor
      to immobilized ELAM-1 IgG could provide T cells with costimulatory signals for
      proliferation in the presence of submitogenic concentrations of anti-CD3
      antibodies. The binding of T cells to the endothelial adhesion receptor GMP-140
      might be important during the initial adhesion process of lymphocytes in
      rejecting grafts.

PMID- 7504347
TI  - Effect of deoxyspergualin on the endocrine function of the rat pancreas.

PMID- 7504348
TI  - The use of TSQ as an islet-specific stain for purification of islets by
      fluorescence-activated sorting.

PMID- 7504349
TI  - Neural tube defects.

PMID- 7504350
TI  - 1H nuclear magnetic resonance spectroscopy identifies neural cell types: a
      promising step for neuroimaging?

PMID- 7504351
TI  - On establishing the genetic basis of mental disease.
AB  - Many of the recent studies reporting genetic linkages for mental illnesses such
      as schizophrenia and manic depression have been retracted. The authors of this
      article argue that the fundamental reason for the difficulties in this research
      field lies in the strongly held preconceived belief that the primary cause of
      these illnesses is in fact genetic. All scientists hold preconceived ideas.
      However, such ideas are more likely to result in erroneous conclusions in the
      study of human behavior than in other more 'objective' research areas. Moreover,
      it is especially important that researchers studying human behavior be aware of
      their biases and learn to compensate for them because of the social consequences
      of their work.

PMID- 7504352
TI  - The dynamic clamp: artificial conductances in biological neurons.
AB  - The dynamic clamp is a novel method that uses computer simulation to introduce
      conductances into biological neurons. This method can be used to study the role
      of various conductances in shaping the activity of single neurons, or neurons
      within networks. The dynamic clamp can also be used to form circuits from
      previously unconnected neurons. This approach makes computer simulation an
      interactive experimental tool, and will be useful in many applications where the
      role of synaptic strengths and intrinsic properties in neuronal and network
      dynamics is of interest.

PMID- 7504353
TI  - Presynaptic inhibition in the hippocampus.

PMID- 7504354
TI  - Genetic and molecular advances in Alzheimer's disease.
AB  - The abnormal deposition of amyloid beta protein (A beta) in the brain is the
      major neuropathological characteristic of Alzheimer's disease (AD). The disease
      in some early-onset familial cases develops as a result of mutations in the gene
      coding for the beta-amyloid precursor protein (beta APP) and in the majority of
      the rest appears to be caused by an unidentified gene on chromosome 14. Only one
      of the beta APP gene mutations has been associated with aberrant beta APP
      processing, resulting in an excess production of A beta in vitro, a result
      suggesting that there might be excessive A beta cleavage from beta APP in AD in
      vivo. By contrast with the beta APP mutants, no particular allele of the
      apolipoprotein E (APOE) gene predicts the disease completely but one allele is
      associated with the disease suggesting APOE is a risk locus for AD. This
      discovery has been linked to increased deposition of A beta in those cases
      carrying the risk allele. However, the genetic evidence is currently not
      sufficient to indicate whether beta APP mismetabolism, direct or indirect A beta
      neurotoxicity or dysfunction of beta APP (or its derivatives) are central to the
      AD process.

PMID- 7504355
TI  - Physiological production of the beta-amyloid protein and the mechanism of
      Alzheimer's disease.
AB  - The progressive deposition of the beta-amyloid peptide in the brain and its
      microvasculature is an invariant feature of Alzheimer's disease that appears to
      precede the onset of dementia by many years. It had been assumed that the
      proteolytic release of beta-amyloid peptide from the transmembrane region of its
      large precursor protein was an aberrant event, requiring prior membrane injury.
      However, it has recently been shown that beta-amyloid peptide is continuously
      secreted from healthy neural and non-neural cells in culture and circulates in
      human CSF and blood. The finding that beta-amyloid peptide is a normal, soluble
      product of cellular metabolism has led to many dynamic studies of its formation
      and clearance in health and in genetic forms of Alzheimer's disease, and should
      facilitate the design of amyloid-inhibiting therapeutics.

PMID- 7504356
TI  - beta-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis
      in Alzheimer's disease.
AB  - Recent findings link altered processing of beta-amyloid precursor protein (beta
      APP) to disruption of neuronal Ca2+ homeostasis and an excitotoxic mechanism of
      cell death in Alzheimer's disease. A major pathway of beta APP metabolism results
      in the release of secreted forms of beta APP, APPss. These secreted forms are
      released in response to electrical activity and can modulate neuronal responses
      to glutamate, suggesting roles in developmental and synaptic plasticity. beta APP
      is upregulated in response to neural injury and APPss can protect neurons against
      excitotoxic or ischemic insults by stabilizing the intracellular Ca2+
      concentration [Ca2+]i. An alternative beta APP processing pathway liberates
      intact beta-amyloid peptide, which can form aggregates that disrupt Ca2+
      homeostasis and render neurons vulnerable to metabolic or excitotoxic insults.
      Genetic abnormalities (e.g. certain beta APP mutations or Down syndrome) and age
      related changes in brain metabolism (e.g. reduced energy availability or
      increased oxidative stress) may favor accumulation of [Ca2+]i-destabilizing beta
      amyloid peptide and diminish the release of [Ca2+]i-stabilizing, neuroprotective
      APPss.

PMID- 7504357
TI  - Carrier-mediated release of neurotransmitters.
AB  - There is growing evidence that neurotransmitters can be released not only by
      exocytosis but also through the membrane carriers responsible for transmitter
      reuptake. Giulio Levi and Maurizio Raiteri review the in vitro and in vivo
      evidence supporting the existence of a carrier-mediated release for different
      classes of transmitters. While the physiological significance of carrier-mediated
      release remains speculative, widely used drugs such as sympathomimetic amines,
      the anorectic drug fenfluramine and some drugs of abuse act in part by
      stimulating monoamine carrier-mediated release. Moreover, antidepressants known
      to inhibit monoamine reuptake, can block carrier-mediated release. This mechanism
      may also come into play in pathological conditions such as ischaemia.

PMID- 7504358
TI  - Neural-immune interactions in sympathetic ganglia.
AB  - Effects of immune cytokines on neuronal gene expression have recently been
      examined in cultured superior cervical (sympathetic) ganglia, a widely used model
      system for the study of neurotransmitter plasticity. Following deafferentation
      and explantation into culture, interleukin-1 causes an up-regulation of the
      neuropeptide substance P as well as of choline acetyltransferase. Tumor necrosis
      factor-alpha has a similar, though less potent, action. Since interleukin-1 was
      ineffective in raising the concentration of substance P in pure neuronal
      cultures, the existence of a non-neuronally derived intermediate was postulated
      and found to exist in interleukin-1-conditioned medium. Antibody neutralization
      of either nerve growth factor or ciliary neurotrophic factor failed to affect the
      ability of interleukin-1 to induce substance P. Inhibition of prostaglandin
      biosynthesis was equally ineffective. However, immunoprecipitation of leukemia
      inhibitory factor from interleukin-1-conditioned medium eliminated substance-P
      inducing activity, suggesting leukemia inhibitory factor as a possible
      interleukin-1-induced intermediate. The ability of interleukin-1 to induce
      leukemia inhibitory factor mRNA strengthens this conclusion. Glucocorticoid
      hormones block the interleukin-1 induction of leukemia inhibitory factor, which
      explains why they block the interleukin-1 induction of substance P.

PMID- 7504359
TI  - The TiPS/TINS lecture: the molecular biology of mammalian glutamate receptor
      channels.
AB  - In native brain membranes the principal excitatory neurotransmitter L-glutamate
      activates cation-conducting channels with distinct biophysical and
      pharmacological properties. Molecular cloning has revealed the existence of 16
      channel subunits that can assemble in homomeric or heteromeric configurations in
      vitro to form receptor channels with disparate functional properties. This review
      describes the different channel types obtained by recombinant means and the
      genetic mechanisms controlling the expression of functionally important channel
      structures.

PMID- 7504360
TI  - Therapeutic potential of excitatory amino acid antagonists: channel blockers and
      2,3-benzodiazepines.
AB  - NMDA and non-NMDA (AMPA/kainate) antagonists have potential in the treatment of a
      diverse group of neurological disorders associated with excessive activation of
      excitatory amino acid receptors. Here Michael Rogawski reviews recent progress in
      the development of therapeutically useful NMDA receptor channel blockers and a
      new class of selective AMPA/kainate receptor antagonists, the 2,3
      benzodiazepines. Research on these novel noncompetitive excitatory amino acid
      antagonists has opened promising new avenues for the development of drugs to
      treat epilepsy, ischaemia, neurodegeneration and Parkinson's disease.

PMID- 7504361
TI  - Iminoglycinuria: a benign type of inherited aminoaciduria.
AB  - The diagnosis of iminoglycinuria was established in two patients on the basis of
      increased urinary excretion of proline, hydroxyproline and glycine in the
      presence of normal plasma concentrations of these respective compounds. Routine
      metabolic screening was performed in these infants in order to find the cause for
      the developmental delay observed in one infant and the siblings deaths noted in
      the family of the other. These two patients gave further support to the previous
      suggestion that renal iminoglycinuria is a benign disorder with no recognizable
      clinical pattern. Its detection, therefore, requires screening programs or amino
      acid studies.

PMID- 7504362
TI  - [Role of pulmonary artery cerclage in congenital cardiopathies. 27 case reports].

PMID- 7504363
TI  - Camel trypanosomosis in Rajasthan, India.
AB  - Blood samples from 240 camels (Camelus dromedarius) were examined for trypanosome
      infection. Of these, 18 (7.50%) were found to be infected using the wet blood
      Giemsa stain technique, while 76 (31.66%) camels were found to be positive for
      Trypanosoma evansi antigen using the double antibody sandwich enzyme-linked
      immunosorbent assay (ELISA). The latter was found to be a more useful method for
      the detection of current infection.

PMID- 7504364
TI  - Influence of protein deficiency on hexachlorocyclohexane and malathion toxicity
      in pregnant rats.
AB  - The effects of protein deprivation and 60 mg hexachlorocyclohexane (HCH)/kg or
      500 mg malathion/kg body weight were studied in pregnant rats fed a diet
      containing 16% (control) or 5% (protein-deficient) casein throughout gestation.
      Three po doses of HCH or malathion on the 6th, 10th and 14th day of gestation
      resulted in maternal toxicity and fetal growth retardation. No skeletal anomalies
      were noted except for poor ossification in the protein-deficient dams, which was
      further exaggerated on exposure to HCH or malathion. Malathion caused more severe
      maternal and fetal toxicity compared to the HCH-dosed rats. Depletion in
      glutathione (GSH) and decreased activities of GSH peroxidase, GSH reductase and
      glucose-6-phosphate dehydrogenase were observed from the protein deficiency and
      pesticide exposure. Impairment of GSH-dependent routes of detoxification was
      noticed from exposure to HCH or malathion during pregnancy. The lipid peroxide
      content was elevated from protein deficiency and was magnified with pesticide
      exposure.

PMID- 7504367
TI  - A truncated form of herpes simplex virus type 1 immediate-early protein Vmw110 is
      expressed in a cell type dependent manner.
AB  - Herpes simplex virus type 1 (HSV-1) encodes five immediate-early (IE) genes, at
      least three of which are involved in the regulation of gene expression. Gene IE-1
      is one of the few HSV-1 genes whose pre-mRNAs are spliced; the IE-1 pre-mRNA
      contains two introns, the second of which contains an in-frame stop codon which
      would terminate IE-1 translation if the intron were not excised. Previous work
      has shown that plasmids which have been constructed so as to express only the
      first two exons of Vmw110 can inhibit gene expression in transfection assays,
      whereas the normal intact protein is an activator of gene expression. In this
      paper we show that this predicted truncated Vmw110 protein is expressed during
      normal HSV-1 infection, and that it must be translated from IE-1 pre-mRNAs which
      retain the in-frame stop codon in the second intron. This truncated product is
      produced in amounts which depend upon the cell type infected. The possible
      consequences of these observations are discussed.

PMID- 7504365
TI  - Phosphorylation of the adenovirus DNA-binding protein and epitope mapping of
      monoclonal antibodies against it.
AB  - To facilitate structure/function studies of the adenovirus type 2 or 5 single
      stranded DNA binding protein (DBP), the epitopes of five anti-DBP monoclonal
      antibodies were mapped. Antibodies 37-3, 38-2, and B6 mapped between DBP residues
      131-174 which corresponds to the host-range or hinge region of the molecule. The
      epitopes for antibodies 16-5 and 18-9 mapped between residues 58-81, and included
      a phosphorylated serine at position 70. Using antibodies 16-5 or 18-9 as
      analytical reagents, approximately 1/2 of the DBP molecules present at late times
      in infected HeLa cells were found to be phosphorylated at serine 70. A similar
      pattern of serine 70 phosphorylation was observed in productively and abortively
      infected monkey cells as well as in an E2A-transformed, DBP expressing cell
      lines. This study also reports the preliminary identification of two new
      phosphorylation sites on Ad2 DBP at serines 160 and 161 (corresponding to serine
      161 on Ad5 DBP). No differences were observed in the phosphorylation of serine
      160/161 in DBP isolated from infected HeLa cells or from productively and
      abortively infected monkey cells. Therefore, phosphorylation of these sites
      cannot account for the block to wild-type adenovirus growth in monkey cells.

PMID- 7504366
TI  - Topology of the major capsid protein P3 of bacteriophage PRD1: analysis using
      monoclonal antibodies and C-terminally truncated proteins.
AB  - Trimeric capsomeres of protein P3 (395 aa) are the main component of the phage
      PRD1 capsid, which encloses a lipid-protein vesicle containing the viral dsDNA
      genome. In this study we characterize a panel of monoclonal antibodies (MAb)
      against P3. The epitopes recognized by the MAbs are analyzed by
      immunoprecipitation of intact virions or of released P3 trimers, and by Western
      blotting using a series of C-terminally truncated P3 molecules. Nine of the MAbs
      recognize epitopes on the virion surface, whereas five require unmasking of
      epitopes by disruption of the virions. Several of the MAbs are capable of
      neutralizing the virus; this is most probably due to virus aggregation by the
      antibodies. Analysis of the C-terminal truncations (the 6 Western blot-positive
      MAbs were used) delineates three major antigenic regions of the protein. The
      epitope of MAb 3T74 is included in the 66 N-terminal amino acids, and is not
      accessible on the virion surface, suggesting that the N-terminus is internally
      located in the capsid. MAbs 3N81 and 3R2 recognize epitopes in the region of
      amino acids 159-168, which is part of the first predicted beta-barrel structure
      of P3. The third antigenic region is in the second predicted beta-barrel, between
      amino acids 217-242, where the epitopes of 3N180, 3P4, and 3T5 map. The
      trimerization of P3 was found to be independent of the non-structural assembly
      factor proteins P10 and P17. Functional studies of the truncated proteins reveal
      that molecules comprising of 294 or more residues from the P3 N-terminus are
      capable of trimer formation.

PMID- 7504368
TI  - Epitope mapping studies with neutralizing and non-neutralizing monoclonal
      antibodies to the G1 and G2 envelope glycoproteins of Hantaan virus.
AB  - Epitopes recognized by three G1-specific and two G2-specific neutralizing
      monoclonal antibodies to Hantaan virus were mapped by sequence analyses of the
      complete M genome segments of neutralization escape variant viruses. For each
      variant, we detected nucleotide sequence substitutions which resulted in a single
      amino acid change in either the G1 or G2 protein. Serological properties of the
      variant viruses correlated with changes identified by nucleotide sequence
      analyses. To map epitopes recognized by three G1-specific and six G2-specific,
      non-neutralizing monoclonal antibodies, we prepared genes, truncated at the
      carboxy terminal coding regions of G1 or G2, and expressed them with baculovirus
      recombinants or transiently in a vaccinia/T7 RNA polymerase system. Reactivities
      of the monoclonal antibodies with the truncated proteins were monitored by immune
      precipitation of the radiolabeled, truncated glycoproteins. We determined that
      all three of the G1-specific antibodies reacted with truncated proteins, which
      retained the amino terminal one-third of G1, but lost reactivity with shorter G1
      proteins. The G2-specific antibodies only recognized G2 proteins, which retained
      approximately 80% of the G2 gene.

PMID- 7504369
TI  - Increased expression of alpha 4 beta 1 and alpha 5 beta 1 integrins on HTLV-I
      infected lymphocytes.
AB  - T cells interact with the extracellular matrix via integrin receptors and these
      interactions affect both cellular localization and proliferation. The importance
      of these interactions in retrovirus-induced diseases, however, remains less
      clear. In the present study, we investigated changes in T cell adhesion to
      extracellular matrix proteins by HTLV-I expressing cell lines and human
      peripheral blood lymphocytes infected with HTLV-I by cocultivation. Cell lines
      and acutely infected primary peripheral blood lymphocytes demonstrated enhanced
      adhesion to fibronectin. Acute infection of peripheral blood lymphocytes
      increased the expression of alpha 5 beta 1 and alpha 4 beta 1 integrins.
      Antibodies to the alpha 4, alpha 5, and beta 1 subunits inhibited attachment of
      infected cells to fibronectin. We conclude that HTLV-I infection is associated
      with an increase in the expression of both the classical fibronectin receptor and
      the receptor for the alternatively spliced domain of fibronectin on peripheral
      blood lymphocytes. HTLV-I-related alterations in cell surface adhesion molecules
      may contribute to the abnormal proliferation of T cells in adult T cell leukemia
      (ATL) or to the abnormal localization of activated or infected T cells to the
      central nervous system of patients with tropical spastic paraparesis/HTLV-I
      associated myelopathy (TSP/HAM).

PMID- 7504370
TI  - In vivo priming and activation of memory cytotoxic T-lymphocytes (CTL) by a
      chimeric simian virus 40 T antigen expressing an eight amino acid residue herpes
      simplex virus gB CTL epitope.
AB  - The simian virus 40 (SV40) large T antigen was used as an immunogenic vector to
      express a herpes simplex virus type 1 (HSV-1) glycoprotein B (gB), H-2Kb
      restricted cytotoxic T lymphocyte (CTL) recognition epitope corresponding to
      amino acid residues 498-505. Immunization of naive, C57BL/6 mice with a cell
      line, B6/350gB, expressing the chimeric T antigen was able to induce the
      generation of gB498-505-specific CTL in both the lymph nodes and the spleen.
      Splenic-derived, gB498-505-specific memory CTL (CTLm) were detected in these mice
      for at least 6 months following immunization at a slightly lower frequency than
      in those mice immunized with infectious HSV-1. B6/350gB was also able to activate
      in vitro gB498-505-specific memory CTL obtained from mice previously challenged
      with HSV. Overall, these findings support the use of a chimeric T antigen as a
      vector in determining the immunogenic potential of individual CTL epitopes and to
      assess their potential contribution in inducing a protective immune response in
      vivo.

PMID- 7504371
TI  - Photodynamic inactivation of radiation leukemia virus produced from hypericin
      treated cells.
AB  - Hypericin is a polycyclic, aromatic, naphthodianthrone which has been shown to
      possess in vivo and in vitro antiretroviral activity. To gain further insight
      into the mechanism(s) by which hypericin exerts its antiretroviral effects, we
      have studied Radiation Leukemia virus (RadLV) produced from cells pulse-treated
      with hypericin. Hypericin-treatment did not inhibit retroviral production or the
      proteolytic cleavage of the gag-encoded precursor proteins. Rather, hypericin was
      found to be associated with RadLV particles, the retrovirions showed an increased
      density in sucrose, and the RadLV protein banding patterns were altered. RadLV
      produced from hypericin-treated cells was rendered noninfectious upon exposure to
      visible light. Our results suggest that RadLV produced from hypericin-treated
      cells is inactivated by a hypericin-mediated photodynamic process.

PMID- 7504372
TI  - A chimeric human immunodeficiency virus type 1 TAR region which mediates high
      level trans-activation in both rodent and human cells.
AB  - Trans-activation of the HIV-1 LTR by the Tat protein functions by a novel
      mechanism which involves the direct interaction of the Tat protein and cellular
      factors with nascently transcribed viral RNA encoding the Tat responsive element
      (TAR). Rodent cells do not efficiently support HIV-1 Tat activity because of a
      deficiency of human-specific factor(s). Human chromosome 12 appears to encode one
      of these Tat cofactors. We have designed chimeric TAR sequences which contain the
      heterologous RNA sequence derived from the bacteriophage R17 genome which binds
      to the bacteriophage MS2 coat protein. These chimeric TAR constructs were co
      transfected into rodent and human cells with a plasmid encoding a chimeric Tat
      protein which contains the RNA binding domain of the MS2 coat protein. TAR
      constructs which contain the MS2 coat protein binding region inserted into the
      three nucleotide "bulge" region support a high level of trans-activation by Tat
      MS2 coat protein chimeras in both human and rodent cells. This result suggests
      that the human-specific Tat cofactor(s) may act to allow Tat to interact
      effectively in a ribonucleoprotein complex which includes Tat, cellular factors,
      and TAR RNA.

PMID- 7504374
TI  - Antibodies to hepatitis C virus in blood donors and polytransfused patients of
      Macau (southeast China)

PMID- 7504373
TI  - Predictive value of screening tests for persistent hepatitis C virus infection
      evidenced by viraemia. Japanese experience.
AB  - In November 1989, Japanese Red Cross Blood Centres started screening for
      hepatitis C virus (HCV) with enzyme-linked immunosorbent assay (Elisa) for the
      C100-3 viral peptide as the first such nationwide programme in the world.
      Thereafter post-transfusion non-A non-B hepatitis (PTNANBH) was reduced by 61
      80%, but this was not as complete a success as our programme to prevent post
      transfusion hepatitis B by screening for high titer hepatitis B core antibody,
      which we began in the same period. In order to acquire more effective control of
      PTNANBH, the HCV core-related antigen (GOR, N14) and second-generation Elisa
      (Ortho2, Abbott2) and second-generation antigen agglutination (PA, PHA) tests
      have been employed. Among 16,500 donors in 11 blood centers, 365 were
      serologically positive by at least one of these tests. Among these, HCV RNA was
      detected in 138 units and the remaining 227 were HCV RNA negatives. The
      effectiveness of these serological tests to detect HCV RNA-positive status were
      analyzed. Passive haemagglutination and particle agglutination (PHA and PA) tests
      were highly effective to predict HCV viraemia among blood donors. Also, these
      tests can easily determine antibody titre. By either PHA or PA, all units with >
      or = 2(12) agglutination titre (120 and 122 units) were HCV RNA positive and all
      agglutination-positive units with serum alanine aminotransferase level higher
      than 35 Karmen units were HCV RNA positive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504375
TI  - Hepatitis C antibody (anti-HCV) prevalence in Brazilian patients with sickle cell
      diseases.

PMID- 7504377
TI  - [Follow up results of radical correction of Fallot's syndrome].
AB  - In the years 1981-1989 in the Department of Cardiosurgery, Institute of
      Cardiology, Medical Academy in Lodz, 39 patients with Fallot's syndrome were
      subjected to radical correction of the congenital heart disease. In 18 cases the
      correction was preceded by a palliative operation carried out on the average four
      years before the radical correction of the congenital heart disease. During the
      early postoperative period seven patients died which accounted for 17%. Out of 39
      patients treated surgically, 32 were in I or II haemodynamic grade according to
      NYHA.

PMID- 7504376
TI  - [Algodystrophy--Sudeck syndrome].
AB  - Modern views are presented on the development of algodystrophy illustrated with
      own material with a detailed description of characteristic cases. In the whole
      material of 175 patients, four age groups, and two groups according to trauma
      site (hand and foot) were isolated. All patients were subjected to clinical, X
      ray, and some to radioisotope examinations. Greatest number of cases of
      algodystrophy was found in the age group over 60 years which confirmed the
      observations of other authors. On the basis of the presented material the authors
      think that of greatest importance are early diagnosis, treatment with of greatest
      importance are early diagnosis, treatment with analgesics, blood flow improving
      drugs, and salmon calcitonin, and rehabilitation treatment. It seems also that
      treatment with magnetic field may be beneficial--however, too small material of
      patients makes general conclusions impossible.

PMID- 7504379
TI  - Long-lasting T-cell reactivity to Mycobacterium leprae antigens in human
      volunteers vaccinated with killed M. leprae.
AB  - A trial with a candidate anti-leprosy vaccine based on killed Mycobacterium
      leprae was started in Norway in 1983 to evaluate its toxicity and efficacy to
      induce cell-mediated immunity (CMI) in BCG-vaccinated healthy volunteers. The
      vaccinated subjects were found to be free of unacceptable side-effects and their
      T cells showed elevated proliferative response to M. leprae up to 1 year
      postvaccination. When tested in 1991, 8 years after vaccination, peripheral blood
      mononuclear cells from the same volunteers showed a persistent high proliferative
      response to M. leprae. From a total of 147 T-cell clones established from these
      subjects, 26 clones were specific to M. leprae and the remaining T-cell clones
      responded to M. leprae as well as to BCG and other cultivable mycobacteria. The
      epitopes recognized by the M. leprae-specific T-cell clones were present on
      several protein antigens including the 18 kDa and the 65 kDa heat shock proteins.
      A dominant epitope, peptides 38-50 on the M. leprae 18 kDa heat shock protein,
      which was recognized by M. leprae-specific T cells 1 year after vaccination, was
      also recognized 8 years after vaccination by the same donor. This is the first
      report demonstrating the unique property of killed M. leprae with respect to the
      induction of long-lasting T-cell reactivity towards M. leprae antigens in humans.

PMID- 7504378
TI  - High-titre antibodies to a foreign epitope elicited by affinity-purified hybrid
      LamB proteins.
AB  - A monoclonal antibody to the LamB protein, named LBS-1, was developed and
      characterized. It was then covalently bound to Sepharose and used to purify
      hybrid LamB proteins from Escherichia coli crude extracts. A peptide of the
      interferon-gamma (IFN-gamma) NH2-terminal region, inserted within the LamB
      protein, was used as a model to assess immune response in mice injected with
      sonicated E. coli extract or with affinity-purified hybrid LamB protein. None of
      the mice immunized with the whole bacterial extract produced antibodies to IFN
      gamma. On the other hand, all the mice immunized with the purified protein
      developed high-titre anti-IFN-gamma antibodies. These results might be due to the
      presence of bacterial components capable of masking the LamB protein to the
      immune system. The use of affinity-purified LamB proteins may constitute in some
      instances a more effective way of generating an immune response against foreign
      epitopes as opposed to whole bacterial antigens.

PMID- 7504380
TI  - Synthetic gonadotrophin-releasing hormone (GnRH) vaccines incorporating GnRH and
      synthetic T-helper epitopes.
AB  - A vaccine against the gonadotrophin-releasing hormone (GnRH) is being developed
      as an immunological method for treatment of prostatic hypertrophy, based on the
      observation that active immunization against GnRH leads to the production of anti
      GnRH antibodies which results in the shrinkage of the prostate gland. We have
      been investigating the regulation of anti-GnRH antibody responses by carrier
      molecules. In previous studies we showed that the use of large protein molecules
      as carriers limits the use of such a vaccine owing to potential problems of
      carrier-induced anti-haptenic suppression. In this report we show that synthetic
      T-helper epitopes can be used as carriers for the generation of anti-GnRH
      antibody responses.

PMID- 7504381
TI  - Immunogenicity of a synthetic oligopeptide corresponding to antigenically common
      T-helper and B-cell neutralizing epitopes of the major outer membrane protein of
      Chlamydia trachomatis.
AB  - Sexually transmitted diseases (STDs) caused by Chlamydia trachomatis are an
      important public health problem and a vaccine to prevent or control these
      diseases is badly needed. The major outer membrane protein (MOMP) is the
      principal candidate antigen for the development of subunit vaccine against
      chlamydial STDs. The immunogenicity of a synthetic oligopeptide, termed A8-VDIV,
      corresponding to MOMP sequences containing both C. trachomatis species common T
      helper (A8) and B-cell (VDIV) epitopes was studied in mice and non-human
      primates. Six of eight H-2 congenic mouse strains immunized with peptide A8-VDIV
      produced high-titre IgG antibodies against the VDIV B-cell portion of the
      oligopeptide. Fine mapping of the anti-peptide antibodies by pepscan ELISA showed
      that each of the responding mouse strains made antibodies reactive with a species
      common septmeric neutralizing epitope 298LNPTIAG304 contained in the VDIV
      sequence. The mouse anti-peptide antibodies reacted with intact C. trachomatis
      elementary bodies (EBs) by ELISA and neutralized chlamydial infectivity for
      cultured eukaryotic cells with sub-species specificity. Three cynomolgus monkeys
      were immunized with peptide A8-VDIV and their IgG antibody responses were
      similarly studied. All three monkeys produced IgG antibodies which reacted with
      the VDIV peptide and which recognized the species-common LNPTIAG neutralizing
      site within the VDIV sequence. Monkey anti-peptide antibodies bound to intact C.
      trachomatis EBs and were neutralizing in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504383
TI  - Chronic active anti-HCV positive hepatitis and post-hepatitis C cirrhosis: role
      of interferon.

PMID- 7504382
TI  - Cytomorphology of combined hepatocellular-cholangiocarcinoma in fine needle
      aspirates of the liver. A report of two cases.
AB  - Combined hepatocellular-cholangiocarcinoma (HCC-CC) is rare, constituting much
      less than 5% of all primary liver cancers. Its dual histologic and cytologic
      differentiation may be a major problem in the differential diagnosis of fine
      needle aspiration biopsies (FNABs) of the liver. We describe two cases of
      combined HCC-CC, both examined initially by FNAB. Cytologic smears were markedly
      cellular, with a population of slightly to moderately pleomorphic neoplastic
      cells, often arranged in cohesive cords and columns resembling anastomosing
      hepatic plates. Many of these cells had centrally placed nuclei and a moderate
      amount of granular, eosinophilic cytoplasm. Other cellular groups were arranged
      in acinar formations, with eccentric nuclei and intraluminal and cytoplasmic
      mucin production. Both types of cells were positive for cytokeratin and
      carcinoembryonic antigen; in one case the carcinoma cells were also focally
      positive for alpha-fetoprotein. Although these neoplasms may pose diagnostic
      challenges, our experience suggests that HCC-CC may be suspected or even
      diagnosed by FNAB.

PMID- 7504384
TI  - [Biological properties and clinical application of filgrastim (G-CSF)].
AB  - Granulocyte--colony stimulating factor (G-CSF, filgrastim) is a glycoprotein
      hormone of the hematopoietin family that primarily influences the proliferation
      and differentiation of neutrophilic granulocytic precursors. As with all glyco
      protein hormones, G-CSF interacts with target cells by binding to specific cell
      surface receptors. It stimulates proliferation, differentiation and activation of
      cells of the neutrophil--granulocyte lineage and has been investigated as therapy
      for patients with various neutropenic conditions. A major use for recombinant G
      CSF therapy will be in ameliorating the neutropenia which follows cytoreductive
      chemotherapy. The increase in neutrophils produced by this factor render it a
      useful treatment for conditions such as congenital, acquired and cyclic
      neutropenias. It may be an effective therapy in myelodysplasia and aplastic
      anaemia. G-CSF is also useful in accelerating the recovery of transplanted bone
      marrow in patients with leukaemia, lymphoma and solid tumors. G-CSF is well
      tolerated. The most frequently reported adverse effect is mild to moderate bone
      pain.

PMID- 7504385
TI  - Application of hematopoietic growth factors (G-CSF and GM-CSF) in the treatment
      of chemotherapy-induced or idiopathic bone marrow failure.
AB  - Fifteen patients with various myeloid and lymphoid neoplasias after receiving
      highly myelotoxic chemotherapy were treated with a single daily dose of 5
      micrograms/kg of GM-CSF. G-CSF at a daily dose of 5-8 micrograms/kg was used in
      four patients with severe pancytopenia in the course of acute or chronic lymphoid
      leukemia treated with cytotoxic agents, and in two patients with idiopathic
      aplastic anemia. The administration of cytokines was provided for 4-10 days GM
      CSF increased the WBC in twelve out of fifteen patients, mainly because of an
      increase in the number of neutrophils. Six patients receiving GM-CSF demonstrated
      rapid platelet recoveries. The rapid increase of the WBC was observed in all G
      CSF treated patients. In one patient with aplastic anemia the WBC/ANC decreased
      rapidly to the initial values after the cessation of the G-CSF therapy. Fast
      platelet recovery was seen in three patients treated with G-CSF.

PMID- 7504386
TI  - [Evaluation of screening and complementary tests for anti-HCV antibodies].
AB  - Screening for antibodies to hepatitis C virus (HCV) in blood donors by second
      generation tests was started on May 1991. On July 1992 obligatory testing of
      every blood or plasma donation was implemented. The incidence of anti-HCV
      evaluated in the first period (236.590 sera) was 1.4%. In the second period
      (296,573 sera) the incidence dropped to 0.9%. 489 sera repeatedly positive in
      screening were examined by a complementary test, 4-RIBA. Compatible positive
      results were obtained in 72.8% of the sera. 9.4% of the sera were negative and
      17.8% gave indeterminate results. Reactivity was most frequently (95.7%)
      encountered to the structural core HCV peptide. The value of 4-RIBA was
      discussed. In conclusion, it was pointed out, that blood donors deferral should
      be based on repeated screening.

PMID- 7504387
TI  - Hydroxyethyl starch as a prime for cardiopulmonary bypass: effects of two
      different solutions on haemostasis.
AB  - Hydroxyethyl starch (HES) is efficacious as a volume expander in cardiac surgical
      patients, but it may impair the haemostatic mechanisms. However, this latter
      effect may be less conspicuous with low molecular weight (LMW) solutions than
      with high molecular weight (HMW) solutions. Therefore, LMW- and HMW-HES solutions
      were evaluated as priming solutions for cardiopulmonary bypass (CPB) with respect
      to their effect on haemostasis. Forty-five patients undergoing coronary bypass
      grafting were prospectively randomised to three groups and received in a double
      blind manner as their CPB prime either 20 ml.kg-1 LMW-HES (Mw 120,000), 20 ml.kg
      1 HMW-HES (Mw 400,000) or Ringer's acetate 2000 ml. The final volume of the prime
      was completed to 2000 ml with Ringer's acetate in the HES groups. Anaesthesia and
      CPB management were standardised. Plasma levels of von Willebrand factor antigen
      and factor VIII procoagulant activity were significantly more depressed after CPB
      in both HES-groups as compared with the crystalloid prime group. In addition,
      APTT was more prolonged and the maximal amplitude of thromboelastographic tracing
      was more decreased in the HES-groups. It is concluded that it may be advisable to
      avoid HES solutions in the CPB prime, especially in patients with an increased
      risk for bleeding after cardiac operations.

PMID- 7504388
TI  - Effects of vascular endothelial growth factor and basic fibroblast growth factor:
      application with corneal grafts on the chorioallantoic membrane.
AB  - The corneae of 17- to 19-day-old chick embryos were dissected and grafted on the
      chorioallantoic membrane (CAM) of 10- to 14-day-old embryos with reincubation
      periods of 3-9 days. After fixation, serial semithin or paraffin sections were
      made. Furthermore, two growth factors were applied together with the corneae. The
      165-amino-acid vascular endothelial growth factor (VEGF165) or basic fibroblast
      growth factor (bFGF) was either pipetted onto the corneae, or pieces of shell
      membrane were soaked in a factor solution, dried and inserted into an incision in
      the corneae. After a reincubation of 4-6 days, serial paraffin sections were
      made. The controls show that the viability of the grafts decreases with
      increasing age of the host CAM. Furthermore, with prolonged reincubation, the
      viable corneae become more and more spherical. Due to this movement, necrotic
      tissue of the CAM is shifted into the center of the sphere. After 9 days, blood
      vessels can be seen growing in the direction of the necrosis. bFGF pipetted onto
      the grafts induces marked proliferation of the stroma of the CAM beneath the
      corneae. Additionally, bFGF carriers inserted into the corneae induce fibrocyte
      ingrowth in the grafts together with a few blood vessels. VEGF165 specifically
      induces vascular growth in the CAM beneath the cornea but did not induce blood
      vessel growth into the grafts. The pros and cons of the method are discussed.

PMID- 7504389
TI  - Increase in RNA and glycogen but not in DNA in developing human macrophages
      proven by integrating microdensitometry.
AB  - In order to quantitate DNA, RNA and glycogen contents of developing macrophages,
      blood monocytes were obtained from 19 healthy human subjects and examined after
      0, 2, 4 and 6 days of suspension culture. Cytochemical staining was carried out
      by standard methods using Feulgen, cuprolinic blue and PAS. All specimens from
      all subjects were stained at the same time. Examination was carried out in an
      integrating microdensitometer, the staining intensities of individual cells being
      measured at appropriate wavelengths. Over the 6 days of culture, highly
      significant increases took place in RNA and glycogen, but no significant change
      was found in DNA content. These findings are taken to indicate that increased
      protein synthesis and the building up of fuel reserves are features of macrophage
      development but that S phase DNA replication does not occur.

PMID- 7504390
TI  - [Experimental studies on therapeutic effect of rat monoclonal antibody-bleomycin
      A6 conjugate against human colorectal cancer].
AB  - Bleomycin A6 (A6), a single component of bleomycin complex, is highly active
      against human colon and cecum cancer cells in vitro and xenografts in nude mice.
      R19, a rat monoclonal antibody against human cecum cancer Hce-8693 cells, was
      linked to A6. R19-A6 conjugate retained complete activity of McAb R19 and 10%
      activity of A6. As determined by clonogenic assay with human cecum cancer Hce
      8693 cells for 1 hour exposure. The 50% inhibitory concentration (IC50) values
      for R19-A6, A6 and M3-A6 (conjugate of irrelevant Mc-A6) were 0.019, 1.05 and
      1.00 mumol/L, respectively. The effect of the conjugate R19-A6 was 55-fold
      stronger than that of free A6 and 53-fold than irrelevant conjugate M3-A6.
      Clonogenic assay with human colon cancer HT-29 cells showed that the IC50 values
      were 0.078 mumol/L and 4.0 mumol/L for R19-A6 and free A6, respectively. The
      cytotoxicity to Hce-8693 and HT-29 cells was markedly blocked by unconjugated
      McAb R19 but not by irrelevant McAb MARK-3. The R19-A6 conjugate exerted 90%
      inhibition on the growth of cecum cancer Hce-8693 xenografts in nude mice,
      whereas equivalent doses of free A6, R19 plus A6 mixture and M3-A6 showed 52%,
      34% and 48% inhibition, respectively. Histopathological examination showed no
      toxic changes in the heart, lung, liver, kidney and bone marrow in the R19-A6
      conjugate treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504391
TI  - [Inhibition of 5 calcium channel blockers on H2O2 release from mouse peritoneal
      macrophages].
AB  - After the peritoneal macrophages from mice were incubated with different
      concentrations of calcium channel blockers for 3 h at 37 degrees C, the
      macrophages were stimulated with opsonized zymosan for 1.5 h at 37 degrees C. The
      released H2O2 was measured by fluorescence assay. The results showed that
      verapamil (Ver), nifedipine (Nif), nicardipine (Nic), nimodipine (Nim), and
      nitrendipine (Nit) reduced the H2O2 release significantly in a dose-dependent
      manner. The IC50 values (mumol.L-1) were 30, 50, 49, 63, and 92 for Nic, Nif,
      Nim, Nit, and Ver, respectively. There was slight inhibition of dihydropyridine
      (Bay k 8644) 10 mumol.L-1 on H2O2 release. When Bay k 8644 at above concentration
      combined with Ver, Nim, and Nit 25 mumol.L-1, respectively, the inhibitions of
      Ver, Nim, and Nit on H2O2 release were increased 32%-40%. Above results showed
      that on the inhibition of H2O2 release, the effects of dihydropyridines calcium
      channel blockers were greater than that of Ver, and the effects of Nic and Nif
      were greater than those of Nim and Nit. The acting sitei of Bay k 8644 at high
      concentration (10 mumol.L-1 and over) was probably different from that of typical
      calcium channel blockers Nim, Nit, and Ver in macrophages.

PMID- 7504392
TI  - Therapy evaluation and diagnostic accuracy in neuroendocrine tumours: assessment
      of radiological methods.
AB  - The diagnostic accuracy of ultrasonically guided biopsy-gun biopsies was assessed
      in a group of 47 patients with suspected pancreatic carcinoma. A correct
      diagnosis with the aid of biopsy was obtained in 44 of the 47 patients (94%). In
      3 patients with a carcinoma of the pancreas the correct diagnosis was not
      obtained with the first biopsy. In 2 of these 3 patients, a simultaneous biopsy
      of a liver metastasis revealed the presence of malignant tumour growth. No major
      complications occurred. Biopsy-gun biopsy of the pancreas is considered a useful,
      reliable and non-traumatic method for the diagnosis of pancreatic malignancy.
      Twenty-five patients with known neuroendocrine tumour disease were biopsied with
      1.2 mm and 0.9 mm biopsy-gun needles to evaluate the respective diagnostic
      accuracy of the 2 needle sizes. The influence of treatment-related fibrosis on
      the histopathological diagnosis was also evaluated. The overall diagnostic
      accuracy with the 0.9 mm needle was 69% as compared to 92% with the 1.2 mm
      needle. This difference, however, seems more related to needle guiding
      difficulties with the 0.9 mm needle than to insufficient tissue yield. The
      increased amount of fibrous tissue due to interferon treatment did not seem to
      negatively influence the diagnostic accuracy. In order to assess the diagnostic
      accuracy rate for radiologists with different experience of biopsy procedures 175
      cases of renal biopsy-gun biopsies were evaluated. No statistical significant
      difference was found between the different operators. Provided with detailed
      instruction even operators with limited experience produced biopsy results equal
      to those of operators with extensive practice in ultrasound-guided biopsies. The
      automated sampling performance of the biopsy-gun, with a consistent high
      diagnostic sampling rate (96%), was believed to be responsible for these results.
      The role of duplex Doppler ultrasound in monitoring interferon treatment-related
      changes in carcinoid metastases was evaluated. The patients were divided into 4
      groups: untreated (n = 10), progressive disease (n = 17), stable disease (n = 20)
      and objective response (n = 18). No significant differences in Doppler values
      were found between the groups, and at present duplex Doppler ultrasound does not
      seem to play a role in the evaluation of tumour therapy in carcinoid
      patients.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504393
TI  - FK506 therapy of experimental autoimmune myocarditis after onset of the disease.
AB  - Preventive effects of FK506 on autoimmune myocarditis have been demonstrated, but
      the therapeutic efficacy of the agent in established myocarditis yet remains to
      be assessed. In this study, effects of FK506 on experimental autoimmune
      myocarditis were investigated by the use of the agent after the onset of the
      disease. Lewis rats were immunized with either cardiac myosin or bovine serum
      albumin (BSA) in complete Freund's adjuvant. The onset of the disease was
      ascertained by examining randomly chosen cardiac myosin-immunized rats. Animals
      were divided into four groups: the BSA-immunized saline-treated group (group A, n
      = 6); the BSA-immunized FK506-treated group (group B, n = 6); the myosin
      immunized saline-treated group (group C, n = 6); and the myosin-immunized FK506
      treated group (group D, n = 11). Saline or 1.0 mg/kg/day of FK506 were
      intramuscularly injected from day 16 to day 27. All the rats were put to death on
      day 28. Rats of group C became severely ill by the third week, while in contrast,
      rats of group D remained active, as did rats of groups A and B. The heart
      weight/body weight ratio was significantly lower in group D than in group C rats.
      Group mean values were 3.48 +/- 0.10 gm/kg for group A, 3.48 +/- 0.16 gm/kg for
      group B, 4.94 +/- 0.66 gm/kg for group C, and 3.88 +/- 0.43 gm/kg for group D.
      Rats of group C showed severe myocarditis with mononuclear cell infiltration,
      myocardial necrosis, and interstitial edema.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504394
TI  - Carcinoma of the breast arising in microglandular adenosis.
AB  - Breast carcinoma arose in or in conjunction with microglandular adenosis (MGA) in
      14 of 60 (23%) patients with MGA listed in the authors' files. This article
      describes the clinicopathologic and immunohistochemical features and prognosis of
      these carcinomas. The median patient age was 47 years (range, 26-68 years). All
      patients had a mass. Six (43%) had a family history of breast carcinoma. Lymph
      node metastases were found in 3 of 11 axillary dissections. Ten patients treated
      by mastectomy were recurrence-free, with a median follow-up of 57 months (range,
      3-108 months). Two of three patients treated by excisional surgery were
      recurrence-free 12 and 105 months later. The third woman had bone metastases at
      51 months and was alive 98 months after treatment. Carcinoma arose in the MGA in
      13 patients. In these patients, in situ carcinoma was found in expanded MGA
      glands composed of cells with vesicular poorly differentiated nuclei. One patient
      with benign MGA had carcinoma develop in the opposite breast that was not
      associated with MGA. When it arose in MGA, basement membranes were present in
      benign MGA and in situ carcinoma but tended to be disrupted in invasive foci that
      appeared to be formed by coalescent MGA glands. Strong immunoreactivity for
      cytokeratin, S-100, and cathepsin D was detected in carcinomas. Two carcinomas
      had nuclear progesterone receptors, and one of these had estrogen receptors. One
      carcinoma had positive findings for HER-2neu, and four had immunoreactivity for
      p53 protein. The following conclusions were drawn from these observations: (1)
      carcinomas arising in MGA have a distinctive histopathologic pattern; (2) the
      carcinomas are composed of epithelial cells (cytokeratin positive, actin
      negative) that are strongly immunoreactive for S-100 protein and cathepsin D; and
      (3) with a median follow-up of nearly 5 years, patients with these carcinomas had
      a relatively favorable prognosis, despite histopathologic and immunohistochemical
      features usually associated with a poor prognosis.

PMID- 7504395
TI  - Nitric oxide. Biochemistry, pathophysiology, and detection.
AB  - Nitric oxide is generated from the terminal guanidino nitrogen of L-arginine
      yielding citrulline. This reaction is catalyzed by two major types of nitric
      oxide synthase: inducible and constitutive. Nitric oxide is a gaseous mediator
      responsible for a variety of physiologic phenomena. Its short half-life in
      biologic systems has created problems in its direct determination. Many
      experiments depend on the use of inhibitors of nitric oxide synthase to provide
      indirect evidence for the involvement of nitric oxide. Spectroscopic and
      electrochemical methods are the best for the direct measurement of nitric oxide;
      however, the advantages and disadvantages of each technique should be considered
      carefully before a specific method is selected.

PMID- 7504396
TI  - Serum lipase levels in nonpancreatic abdominal pain versus acute pancreatitis.
AB  - OBJECTIVE: 1) To determine whether serum lipase is elevated in patients with
      nonpancreatic abdominal pain, and 2) to compare the levels of serum lipase and
      serum amylase found in patients with nonpancreatic abdominal pain with those
      found in acute pancreatitis in order to differentiate between the two groups.
      METHODS: Serum lipase and amylase levels were estimated in 95 patients with
      nonpancreatic abdominal pain (group A). These levels were then compared with
      those found in 75 patients with acute pancreatitis (group P). RESULTS: Serum
      amylase in group A ranged from 11 to 416 U/L [mean 58 +/- 46 (SD)]. Three
      patients (3.3%) had raised amylase levels. The maximum elevation noted in this
      group was 416 U/L. Serum amylase in group P ranged from 124 to 13,000 U/L (mean
      1620 +/- 1976). Twenty of the 75 patients (27%) in group P had levels that
      overlapped those found in group A. The serum lipase in group A ranged from 3 to
      680 U/L (mean 111 +/- 101). Ten of the 93 patients (11%) had elevated lipase
      levels. The maximum elevation noted was roughly 3 times normal (680 U/L). Serum
      lipase in group P ranged from 711 to 31,153 (mean 6705 +/- 7022). None of the
      patients in group P had levels that overlapped those found in group A. The
      sensitivity of a serum lipase level > 3 normal in detecting acute pancreatitis
      was 100% and the specificity was 99%. The corresponding figures for serum amylase
      were 72% and 99%, respectively. CONCLUSION: A serum lipase level > 3 normal has a
      better diagnostic accuracy than serum amylase in differentiating nonpancreatic
      abdominal pain from acute pancreatitis.

PMID- 7504397
TI  - Effects of ethanol on the motility of papillary sphincter and exocrine pancreas
      in the monkey.
AB  - The effects of acute and chronic ethanol administration on the motility of the
      papillary sphincter, pancreatic duct pressures, and exocrine pancreas were
      studied. Acute administration (n = 5) significantly reduced the peak pressure of
      the papillary sphincter from 84.2 +/- 19.6 to 15.8 +/- 3.0 mm Hg (p < 0.05) and
      increased the frequency from 0.041 +/- 0.002 to 0.067 +/- 0.005/s (p < 0.01).
      Chronic administration (n = 5) significantly increased pancreatic duct pressure
      and frequency of the papillary sphincter from 8.6 +/- 2.9 to 22.1 +/- 2.9 mm Hg
      (p < 0.01) and from 0.039 +/- 0.002 to 0.071 +/- 0.004/s (p < 0.01),
      respectively. However, it reduced the peak pressure of the papillary sphincter
      from 84.8 +/- 15.1 to 21.1 +/- 2.8 mm Hg (p < 0.05). Electron microscopy showed
      dilation and a concentric arrangement of the rough endoplasmic reticulum in the
      acinar cells. The exocrine function test showed an increased concentration and
      output of bicarbonate, protein, and amylase. These findings suggest that chronic
      alcohol intake may cause papillary dysfunction and pancreatic exocrine
      hypersecretion, which could play a role in increasing pancreatic duct pressure.

PMID- 7504398
TI  - Transjugular intrahepatic portosystemic shunt for palliation of bleeding
      esophageal varices in a patient with severe hemophilia A, advanced HIV infection,
      and cirrhosis.

PMID- 7504399
TI  - Peripheral neuropathy in IgM monoclonal gammopathy and Waldenstrom's
      macroglobulinemia: a frequent complication in elderly males with low MAG-reactive
      serum monoclonal component.
AB  - Peripheral neuropathy (PN) is a frequent complication during primary
      macroglobulinemia (PM), whose immunological genesis has been suggested by various
      authors. This study involved 65 PM patients (44 men and 21 women aged 35-78),
      diagnostically divided into MGUS (31 cases), and indolent (IWM, 24 cases) or
      symptomatic (WM, 10 cases) Waldenstrom macroglobulinemia groups. All patients
      underwent neurological examination, including electrodiagnostic evaluation and
      the determination of the serum titre of antimyelin-associated glycoprotein (MAG).
      An evaluation was made of the prevalence of PN and its correlation with a series
      of hematological variables. The prevalence of PN was 31.6%: of those with PN,
      73.1% manifested both clinical and electrophysiological signs of PN, primarily of
      the demyelinating type. Significant correlations emerged between the presence of
      PN and sex (M vs. F P = 0.0001), advanced age (P = 0.049), low MC levels (P =
      0.025), high anti-MAG titres (P = 0.001) and high Hb levels (P = 0.001). No
      significant correlation with the diagnostic definition of PM was found, although
      the majority of cases with (particularly demyelinating) PN were MGUS or IWM. At
      multivariate analysis, the presence of PN significantly correlated with sex (P =
      0.0001), age (P = 0.019), and anti-MAG titre (P = 0.001). Ten of the 26 PN cases
      showed no MAG reactivity. Significant correlations between PN and low serum MC
      levels/high MAG reactivity support the hypothesis of the antibody-mediated origin
      of many PN, and that the presence of PN depends on the characteristics of the
      proliferating pathological B clone, rather than on the tumor burden of the form
      of macroglobulinemia. Clinically, our data reconfirm the frequency of PN during
      PM and indicate simple clinicohematological variables useful for identifying
      patients at high neuropathic risk.

PMID- 7504400
TI  - Polymorphic pattern of the (AT)X(T)Y motif at -530 5' to the beta-globin gene in
      over 40 patients homozygous for various beta-thalassemia mutations.
AB  - Nucleotide sequence analysis of the 5' beta-globin gene flanking region has been
      carried out for numerous homozygous beta-thalassemia patients with different
      mutations and of various ethnic backgrounds. Four different rearrangements were
      found associated with numerous beta-thalassemia mutations. The (AT)X(T)Y repeat
      motif at -530 showed polymorphic patterns among these patients as follows: All
      ten IVS-II-1 (G-->A) chromosomes and the two with the -87 (C-->G) mutation are
      associated with the (AT)9(T)5 rearrangement, while the 30 IVS-I-6 (T-->C), the 16
      codon 39 (C-->T), the six codon 8 (-AA) chromosomes, and 12 chromosomes with
      different promoter mutations had the (AT)7(T)7 motif. Six chromosomes with the
      promoter mutation at position -29 (A-->G) had the (AT)8(T)6 motif, while an
      (AT)8(T)4 motif appears characteristic for two IVS-I-5 (G-->A and G-->T). No
      direct association between any of the (AT)X(T)Y arrangements and an increased
      gamma gene expression [G gamma and fetal hemoglobin (Hb F)] levels could be
      demonstrated, suggesting that variations in the (AT)X(T)Y motif are common
      polymorphisms.

PMID- 7504401
TI  - Cytokine profile during high-dose rhG-CSF therapy in severe congenital
      neutropenia.
AB  - The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF)
      on cytokine profile was evaluated in a case of severe congenital neutropenia. The
      plasma levels of cytokines were measured before and during rhG-CSF therapy. These
      included G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF),
      interleukin-1 alpha, interleukin-1 beta, interleukin-2 (IL-2), interleukin-3 (IL
      3), interleukin-4, interleukin-6 (IL-6), and tumor necrosis factor-alpha. Soluble
      interleukin-2 receptor (sIL-2R) was measured serially during rhG-CSF therapy.
      Lymphocyte subpopulations including CD2, CD3, CD4, CD8, CD19, CD20, and CD25 were
      also measured, rhG-CSF was administered once daily as a 30-min infusion. The
      patient was treated with increasing dose levels of 100, 200, 400, 800, and 1,600
      micrograms/m2/day. The level of endogenous G-CSF was elevated to 334 pg/ml before
      treatment and GM-CSF, IL-2, IL-3, and IL-6 were slightly elevated. Clinically, he
      showed a moderate response to a high dose of rhG-CSF (1,600 micrograms/m2/day).
      Plasma levels of G-CSF markedly increased during therapy but plasma levels of
      other cytokines did not show significant changes during therapy and lymphocyte
      subpopulations did not significantly change. A drastic increase in sIL-2R
      expression was observed after rhG-CSF infusion and an increase in sIL-2R
      expression occurred even before a major increase in granulocyte counts. These
      results showed that a high dose rhG-CSF therapy may influence the cytokine
      network as judged by the increased sIL-2R expression.

PMID- 7504402
TI  - A novel Mediterranean "delta beta-thalassemia" determinant containing the delta
      (+) 27 and beta (0) 39 point mutations in cis.
AB  - The term delta beta-thalassemia with normal HbF has been recently proposed to
      define heterogenous delta and beta globin gene molecular defects involving the
      same chromosome in cis. Here, we describe a Sardinian family in which three
      members showing microcytosis, border-line HbA2 levels and normal HbF proved to be
      heterozygotes for delta(+) 27 and beta(0) 39 point mutations in cis by allele
      specific oligonucleotide hybridization as well as by ECO 0 109 I endonuclease
      digestion and electrophoresis. As some of these beta-thalassemia carriers shows
      normal HbA2 levels, knowledge of the molecular basis of this novel delta beta
      thalassemia silent phenotype would be useful in thalassemia screening and genetic
      counselling.

PMID- 7504403
TI  - Iron deficiency anemia in hemoglobinopathy.

PMID- 7504404
TI  - Liver disease patterns in hemodialysis patients with antibodies to hepatitis C
      virus.
AB  - The present study correlated histopathology and diagnostic tests in hemodialysis
      patients with serologic markers for hepatitis C virus (HCV). Hepatitis C virus
      infection was found in 65 of 163 patients, as assessed by anti-c100-3 (ELISA 1),
      anti-c22-3, c33C (ELISA 2), and RIBA 2. Several histopathologic patterns were
      found in 33 liver samples from HCV-positive individuals: cirrhosis (n = 3),
      chronic active hepatitis (n = 14), chronic persistent hepatitis (n = 2), isolated
      hemosiderosis (n = 5), reactive hepatitis (n = 6), and others (n = 3). There was
      a positive correlation between time from the first aminotransferase peak and
      histologic damage (P = 0.015). However, the severity of liver disease did not
      correlate with the intensity of RIBA 2 positivity, mean levels or pattern of
      aminotransferases elevation, or markers of past hepatitis B virus infection.
      Moreover, aminotransferases were persistently normal in three patients with
      severe liver disease and were elevated in 10 patients with only mild changes. In
      19 biopsied patients, the presence of plasma HCV RNA was examined by the
      polymerase chain reaction (PCR), which was positive in 15 of the 19 biopsy
      specimens. The ability of PCR positivity to predict the histologic severity of
      the disease was insufficient: four patients with minor liver damage had positive
      PCR and two patients with significant liver damage had negative PCR. No further
      correlations of PCR positivity were found with the other biochemical or
      immunologic markers of HCV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504405
TI  - Nature and frequency of mutations in the alpha-galactosidase A gene that cause
      Fabry disease.
AB  - Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results
      from mutations in the alpha-galactosidase A (alpha-Gal A) gene at Xq22.1. To
      determine the nature and frequency of the molecular lesions causing the classical
      and milder-variant Fabry phenotypes, and for precise carrier detection in Fabry
      families, the alpha-Gal A transcripts or genomic sequences from unrelated Fabry
      hemizygotes were analyzed. In patients with the classical phenotype, 18 new
      mutations were identified: N34S, C56G, W162R, R227Q, R227X, D264V, D266V, S297F,
      D313Y, G328A, W340X, E398X, IVS2+2, IVS5 delta-2,3, 773 delta 2, 954 delta 5,
      1016 delta 11, and 1123 delta 53. Unrelated asymptomatic or mildly affected
      patients with symptoms confined to the heart had a missense mutation, N215S, that
      expressed residual enzymatic activity. Related, moderately affected patients with
      late-onset cardiac and pulmonary manifestations had a small deletion, 1208 delta
      3, that predicted the in-frame deletion of arginine 404 near the terminus of the
      429 residue enzyme polypeptide. In addition, five small gene rearrangements
      involving exonic sequences were identified in unrelated classically affected
      patients. Two small deletions and one small duplication had short direct repeats
      at their respective breakpoint junctions and presumably resulted from slipped
      mispairing. A deletion occurred at a potential polymerase alpha arrest site,
      while the breakpoints of another deletion occurred at an inverted tetranucleotide
      repeat. Screening of unrelated Fabry patients with allele-specific
      oligonucleotides for seven mutations revealed that these were private, with the
      notable exception of N215S, R227Q, and R227X, which were each found in several
      unrelated families from different ethnic backgrounds. The CpG dinucleotide at
      codon 227 was the most common site of mutation, having been altered in 5% of the
      148 unrelated Fabry alleles. These studies revealed that most alpha-Gal A lesions
      were private, that codon 227 was a mutational hot spot, and that certain
      mutations predicted a milder disease phenotype.

PMID- 7504406
TI  - Expression cloning of multiple human cDNAs that complement the phenotypic defects
      of ataxia-telangiectasia group D fibroblasts.
AB  - Ataxia-telangiectasia (A-T) is an inherited human disease of unknown etiology
      associated with neurologic degeneration, immune dysfunction, cancer risk, and
      genetic instability. A-T cells are sensitive to ionizing radiation and
      radiomimetic drugs, offering the possibility of cloning A-T genes by phenotypic
      complementation. We have used this sensitivity to isolate the first human cDNAs
      reported to complement A-T cells in culture. Complementation group D A-T
      fibroblasts were transfected with an episomal vector-based human cDNA library,
      approximately 610,000 resultant transformants were treated with the radiomimetic
      drug streptonigrin-resistant, and nine unrelated cDNAs were recovered from 29
      surviving streptonigrin-resistant clones. Five cDNAs were mapped, but none
      localized to 11q23, the site of A-T complementation group A and C loci. Four of
      the mapped cDNAs conferred mutagen resistance to A-T D fibroblasts on secondary
      transfection. One cDNA was identified as a fragment of dek, a gene involved in
      acute myeloid leukemia. The dek cDNA fragment and pCAT4.5, a 4.5-kb cDNA that
      mapped to 17p11, independently complemented three different phenotypic
      abnormalities of A-T D fibroblasts (mutagen sensitivity, hyper-recombination, and
      radio-resistant DNA synthesis). The pCAT4.5 cDNA did not complement the mutagen
      sensitivity of an A-T group C fibroblast line, suggesting that it represents a
      candidate disease gene for group D A-T. Our results indicate that phenotypic
      complementation alone is insufficient evidence to prove that a candidate cDNA is
      an A-T disease gene. The complementing cDNAs may represent previously
      uncharacterized genes that function in the same pathway as does the A-T gene
      product(s) in the regulation of cellular responses to DNA damage.

PMID- 7504408
TI  - Developmental dysphasias, epilepsy, and Landau-Kleffner syndrome.

PMID- 7504407
TI  - Chagas' disease cardioneuropathy: association of anti-Trypanosoma cruzi and anti
      sciatic nerve antibodies.
AB  - The aim of this work was to study whether Trypanosoma cruzi infection could
      elicit humoral immune response to the well-defined parasite antigen acidic
      fraction separated from T. cruzi cytosol by isoelectric focusing and designated
      fraction IV (FIV) and whether this response could account for some of the
      autoreactive immune response against peripheral nerve components. Chagasic
      patients with positive serology for Chagas' disease were classified as group I (n
      = 12) with normal electrocardiograms (ECG) and no signs of disease, group II (n =
      12) with ECG abnormalities but without cardiomegaly, and group III (n = 12) with
      cardiomegaly and congestive heart failure. Sera from patients in group II showed
      the highest frequency of positive reactivity against FIV. Ninety-two percent had
      titers higher than 1/400 while the percentage for groups I and III was 50%. The
      autoreactive response against human sciatic nerve saline extract (SNS) was
      studied. The binding of IgG to SNS was positive in groups I (58%), II (66%), and
      III (75%) patients. The treatment of SNS with periodate diminished the ability of
      antigens to fix IgG from these chagasic patients. Absorption studies were
      performed to investigate whether FIV and SNS could have cross-reactive epitopes.
      Preabsorption of positive sera with FIV inhibited 48-69% of samples' reactivity
      against antigen. In contrast, preabsorption of positive sera with SNS inhibited
      only 12-23% of samples' reactivity against antigen. Overall, these results
      suggest that FIV-T. cruzi and sciatic nerve components possess some epitopes,
      possibly of a carbohydrate nature, in common. Thus, infection in Chagas' disease
      could overcome the tolerance to self components and could lead to autoimmunity.

PMID- 7504409
TI  - A fluorometric assay for the measurement of nitrite in biological samples.
AB  - The increasing importance of nitric oxide synthase has been underscored by the
      elucidation of its role in a growing number of normal and pathophysiological
      processes. Therefore, techniques for detection of nitrite/nitrate, oxidation
      products of the enzymatic conversion of arginine to citrulline and nitric oxide,
      should serve as useful tools in defining the contribution of NO synthase to these
      processes. We have developed a rapid and sensitive fluorometric assay for
      quantification of nitrite/nitrate based upon the reaction of nitrite with 2,3
      diaminonaphthalene to form the fluorescent product, 1-(H)-naphthotriazole. The
      assay can be used to detect 10 nM nitrite, making it 50-100 times more sensitive
      than the well-known Griess assay. Moreover, the assay is adaptable to a 96-well
      plate format, facilitating the handling of a large number of samples including
      conditioned media from cell culture or the nitrite generated by the purified
      enzyme. Nitrite/nitrate levels in blood can also be monitored using this assay
      when it is combined with a filtration step (to remove hemoglobin) followed by
      conversion of the nitrate to nitrite by nitrate reductase. Thus, this
      fluorometric method combines speed and sensitivity with the handling of a large
      number of samples for the quantification of nitrite generated from in vivo and in
      vitro sources.

PMID- 7504410
TI  - Enzymatic modeling of the oligosaccharide chains of glycoproteins immobilized
      onto polystyrene surfaces.
AB  - A method for the modification of the oligosaccharide moiety of even small amounts
      of purified glycoproteins by enzymatic glycosylation and deglycosylation is
      described. The method includes noncovalent immobilization of the glycoproteins
      onto the polystyrene surface of the wells of microtiter plates used as reaction
      tubes, deglycosylation or glycosylation by incubation either with exoglycosidases
      or endoglycosidases or with glycosyltransferases, and the characterization of the
      modified glycan structures by probing them with lectins. Placental transferrin
      receptor employed as a model glycoprotein was modified in amounts of as little as
      100 ng removing sialic acid residues, hybrid-type glycans or all types of N
      glycans with neuraminidase, endo-beta-N-acetylglucosaminidase H or peptide-N4
      (acetyl-beta-glucosaminyl) asparagine amidase. Asialotransferrin receptor was
      alpha-2,6-sialylated with alpha-2,6-sialyltransferase from rat liver, but could
      not be alpha-2,3-sialylated with alpha-2,3-sialyltransferase from porcine liver.
      Changes in the structure and in the relative amount of the oligosaccharides could
      be monitored semiquantitatively with high sensitivity by the binding of
      digoxigenin-labeled lectins and anti-digoxigenin Fab fragments. The method is
      easy to use, does not require immobilization of the enzymes employed, offers
      simple separation of the enzymes and the product, and leaves the protein intact
      for further studies.

PMID- 7504411
TI  - Anti-hirudin monoclonal antibodies directed toward discontinuous epitopes of the
      hirudin amino-terminal and epitopes involving the carboxy-terminal hirudin amino
      acids.
AB  - A panel of eight monoclonal antibodies (MAbs) was obtained against recombinant
      hirudin variant 2 (rHV2). Specificities of the eight MAbs indicate that four of
      them recognize C-terminal amino acid residues (Group A) and four are directed
      against discontinuous epitopes and recognize a determinant (or determinants)
      within the 43 N-terminal residues (Group B). Using these antibodies recombinant
      hirudins missing one or more C-terminal amino acids can be distinguished from
      molecules with an intact C-terminus either in enzyme immunoassays (EIAs) or by
      immunoaffinity chromatography. A sandwich EIA using the combination of two
      antibodies, one from each group, can quantitate both recombinant hirudin variant
      1 (rHV1) and rHV2 with a detection range from 1 to 10 ng/ml in either buffer or
      plasma. Using only one MAb a competitive antibody capture EIA can quantitate
      recombinant or natural hirudin variants 1, 2, and 3 with a detection range from 5
      to 100 ng/ml for rHV2 with a lysine in position 47 (rHV2K47). None of the
      antibodies recognizes hirudin after it is complexed to alpha-thrombin. The
      ability of any one of these anti-rHV2 antibodies to interfere with hirudin
      binding to alpha-thrombin as measured by inhibition of thrombin's amidolytic
      activity correlates with the range of MAb affinity constants (KD = 3.5 x 10(-9)
      to 1 x 10(-6) M). Incubating hirudin with one antibody from Group A (KD = 3.5 x
      10(-8) M) and one from Group B (KD = 6.0 x 10(-9) M) completely blocks the
      ability of hirudin to bind alpha-thrombin. This MAb panel is thus useful for
      probing the recombinant C-terminal integrity of hirudin, for sensitive free
      hirudin quantitations, and the combined use of two MAbs has potential
      applications as an antidote for hirudin in vivo.

PMID- 7504412
TI  - Destaining of nitrocellulose blots after staining with silver or colloidal gold.
AB  - A new method for destaining blots stained with colloidal gold is described. After
      destaining and restaining, artifacts and discolorations caused by the colloidal
      gold can often be removed. The silver produced by silver enhancement can also be
      selectively removed without affecting the gold stain.

PMID- 7504414
TI  - 32P labeling of nonnucleosidic moieties 5'-attached to oligonucleotides.

PMID- 7504413
TI  - In situ (OP)2-Cu+ mapping of electrophoretically resolved RNA-protein complexes.

PMID- 7504416
TI  - Fragmentation reactions of multiply-protonated peptides and implications for
      sequencing by tandem mass spectrometry with low-energy collision-induced
      dissociation.
AB  - The low-energy collision-induced dissociation reactions of a series of multiply
      protonated peptides have been investigated by tandem mass spectrometry. It is
      known that doubly-protonated tryptic peptides undergo facile fragmentation
      yielding redundant sequence information. The present work has shown that this
      fortunate circumstance seems likely to be the exception rather than the rule. The
      presence of additional basic residues, at positions other than the C-terminus,
      complicates the spectra. The most important such complication discovered in the
      present work involves wholesale transfer of one or two residues from the C
      terminal end of a doubly-charged b fragment to the side chain of a lysine residue
      located near the N-terminus, resulting in mass shifts of the products of
      subsequent second-stage fragmentations. Other examples of the participation of
      the flexible lysine side chain are suggested but could not be confirmed to the
      same extent. The role of Coulombic repulsion in facilitating fragmentation has
      been explored via investigations of triply- and quadruply-protonated basic
      peptides bearing one charge for every three or four amino acid residues. Such
      species yielded almost no sequence information under low-energy collision
      conditions, due to the localization of the ionizing protons on highly basic sites
      rather than on the peptide backbone. It is proposed that collisionally activated
      mobilization of protons from the basic sites, where they are originally located
      upon formation, to the backbone is a necessary condition for structurally useful
      fragmentation to occur. It was not possible, on the basis of the present work, to
      deduce mechanistic generalizations and predictive schemes which would permit
      structural interpretations of such fragment spectra for unknown peptides.

PMID- 7504415
TI  - Preparation of metabolically labeled protein samples for quantitative analysis in
      SDS-polyacrylamide gel electrophoresis.

PMID- 7504417
TI  - Innervation of the dura mater encephali of cat and rat: ultrastructure and
      calcitonin gene-related peptide-like and substance P-like immunoreactivity.
AB  - Ultrastructural, immunocytochemical, and immunoelectron microscopical
      examinations are reported that describe the morphology of putative sensory nerve
      endings in the dura mater encephali of the rat and the cat. Morphometrical
      measurements and reconstructions showed that in the cat the mean diameter of
      axons, the bare area of axolemma, and the content of mitochondria and vesicles
      are highly variable in dural nerve endings. Nerve fibers with a high volume
      density of mitochondria are thought to be sensory, while nerve fibers containing
      many small vesicles are considered autonomic. There is, however, a broad overlap
      of mitochondria-rich and vesicle-rich nerve fibers in the dura, so that
      discrimination between sensory and autonomic endings by these characteristics
      frequently fails. Whole-mount preparations treated cytochemically for detection
      of substance P- and calcitonin gene-related peptide-like immunoreactivity in the
      rat and the cat showed a network of immunopositive nerve fibers in the vicinity
      of dural blood vessels. Most of these peptidergic and probably sensory nerve
      fibers were found terminating in the dural connective tissue far from vessels.
      Calcitonin gene-related peptide-positive nerve fibers were much more abundant
      than substance P-positive fibers. Immunoelectron microscopic preparations
      revealed that calcitonin gene-related peptide- and substance P-like
      immunoreactivity is found in a small proportion of generally thin unmyelinated
      nerve fibers. These proportions were very similar in the rat and the cat.
      Summarizing the recent literature, the morphological characteristics of putative
      sensory nerve fibers in the dura mater are discussed in relation to their
      possible functional significance for neurogenic inflammation and nociception.

PMID- 7504419
TI  - Histochemical study of the human bulbourethral (Cowper's) glands.
AB  - Human bulbourethral glands were reacted histochemically and immunohistochemically
      to identify glycoproteins, some androgen metabolic enzymes, and VIP-like
      immunoreactivity. Neutral/acid mucosubstances were detected in the cytoplasm of
      the tubuloalveolar and ductal cells. 3 beta-, 17 beta-, and 3 alpha
      hydroxysteroid dehydrogenase, G6PD, and 6PGD reactivity were intense in all the
      glandular epithelium. Small amounts of VIP-positive fibres were observed around
      the secretory elements.

PMID- 7504418
TI  - The distribution and characterization of HNK-1 antigens in the developing avian
      heart.
AB  - The heart originates from splanchnic mesoderm and to a lesser extent from neural
      crest cells. The HNK-1 monoclonal antibody is a marker for early migrating neural
      crest cells, but reacts also with structures which are not derived from the
      neural crest. We investigated whether heart structures are HNK-1 positive before
      neural crest cells colonize these target tissues. To that end, we determined the
      HNK-1 antigen expression in the developing avian heart on immunohistochemical
      sections and on Western blots. The HNK-1 immunoreactivity in the developing chick
      heart is compared with data from literature on the localization of neural crest
      cells in chick/quail chimeras. Structures with neural crest contribution,
      including parts of the early outflow tract and the related endocardial cushions,
      the primordia of the semilunar valve leaflets and the aorticopulmonary septum
      were HNK-1 positive. Furthermore, other structures were HNK-1 positive, such as
      the atrioventricular cushions, the wall of the sinus venosus at stage HH 15
      through 21, parts of the endocardium at E3, parts of the myocardium at E6, and
      the extracellular matrix in the myocardial base of the semilunar valves at E14.
      HNK-1 expression was particularly observed in morphologically dynamic regions
      such as the developing valves, the outflow tract cushion, the developing
      conduction system and the autonomic nervous system of the heart. We observed that
      atrioventricular endocardial cushions are HNK-1 positive. We conclude that: a HNK
      1 immunoreactivity does not always coincide with the presence of neural crest
      cells or their derivatives; (2) the outflow tract cushions and atrioventricular
      endocardial cushions are HNK-1 positive before neural crest cells are expected
      (stage HH 19) to enter the endocardial cushions of the outflow tract; (3) the
      observed spatio-temporal HNK-1 patterns observed in the developing heart
      correspond with various HNK-1 antigens. Apart from a constant pattern of HNK-1
      antigens during development, stage-dependent HNK-1 antigens were also found.

PMID- 7504420
TI  - Monoamines in the brain cerebrospinal fluid of facial pain patients.
AB  - The purpose of the study was to assay monoamines in cerebrospinal fluid (CSF)
      obtained from the trigeminal cistern of 64 patients with intractable facial pain.
      The CSF was analyzed for homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5
      HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), end-product markers of
      activity for the dopamine, serotonin, and norepinephrine systems, respectively.
      HVA averaged 121 ng/mL in these facial pain patients, compared to 150 to 550
      ng/mL in 10 studies of ventricular brain CSF in assorted psychiatric and pain
      patients. 5-HIAA averaged 29 to ng/mL in our facial pain patients compared to 60
      to 120 ng/mL in nine studies of ventricular brain CSF in assorted psychiatric and
      neurological patients. Trigeminal cistern CSF MHPG averaged 9 ng/mL, similar to
      the range of 13 studies of lumbar CSF of assorted psychiatric and pain diagnoses.
      These results indicate that (1) the electrochemical detection method provides a
      unique way of accurately measuring nanogram concentrations of multiple monoamines
      in a little as 0.25 mL of CSF; (2) trigeminal cistern and posterior fossa brain
      CSF monoamine metabolites reflect a different profile of dopaminergic and
      serotonergic functioning in these facial pain patients from that previously
      reported with lumbar CSF measurements of other patients; and (3) trigeminal
      sensory ganglion or brain dopamine and serotonin systems may be concomitantly
      dysfunctional in intractable facial pain.

PMID- 7504421
TI  - Immediate adverse reaction to aminophylline.
AB  - We present a patient who experienced an immediate adverse reaction following
      intravenous administration of aminophylline. Skin prick, intradermal, and patch
      tests, RAST and indirect ELISA assays with aminophylline, theophylline and
      ethylenediamine were negative. A positive histamine release test was found only
      with ethylenediamine. Single-blind placebo-controlled challenges were positive
      with aminophylline and negative with theophylline. Our results suggest the
      reaction was a type I hypersensitivity reaction to ethylenediamine, but a
      nonimmune mechanism could not be excluded.

PMID- 7504423
TI  - [Severe acute pancreatitis: diagnostic approaches and therapeutic implications].
AB  - Diagnosis of acute pancreatitis (AP) can be obtained with a high level of
      accuracy by clinical assessment and determination of common laboratory parameters
      such as serum amylase and lipase concentrations. However, the key of an optimal
      management of patients with AP is based on an early discrimination between
      interstitial oedematous and necrotizing forms. The former resolves spontaneously
      whereas parenchymal necrosis acting as a focus for bacteria has a very high
      severity. In this respect, multifactor prognostic scoring systems and new
      biological assessments like C reactive protein are valuable methods for
      forecasting the prognosis of AP. However, these indicators of severity require a
      full 48 hour period of observation. In order to overcome these drawbacks, other
      prognostic criteria have been explored based mainly, on laboratory data. The most
      interesting ones are trypsinogen activation peptides and leucocyte elastase.
      Finally, the more useful tool is computed tomography (CT). Combined with high
      dose intravenous contrast agent, it allows an early identification of necrosis.
      Other goals of computed tomography are an accurate diagnosis of infection by
      guided needle aspirations and a preoperative recognition of devitalized and
      infected tissues, which require a careful surgical necrosectomy. A prolonged
      drainage is always recommended but relative merits of a conventional closed
      drainage and an open one are controversial. Another therapeutic challenge is
      gallstone associated to severe pancreatitis. An early stone removal is advocated
      by some authors but others prefer delayed surgery because of high mortality rates
      in case of emergency surgery. Delayed surgery until biological parameters of
      pancreatitis are normalized seems preferable. An early endoscopic sphincterotomy
      in an attractive alternative method.

PMID- 7504422
TI  - [Control of the ratio of the flow rate of the substitution fluid to the blood
      removal rate during preoperative normovolemic hemodilution].
AB  - Twenty-one patients (mean age 46 +/- 13 years) due to undergo abdominal or ENT
      surgery, presumed to give rise to an important blood loss were included in this
      study. None had any contra-indication to the use of normovolaemic haemodilution
      (NH). Mean initial haematocrit was 40.3 +/- 1.8%. Their estimated total blood
      volume was 4,867 +/- 857 ml. The patients were anaesthetized with thiopentone,
      fentanyl, vecuronium or atracurium. Maintenance was carried out with isoflurane
      (0.5% during NH). Usual haemodynamic monitoring was used throughout. The required
      haematocrit was decided on before starting NH. The amount of blood to be removed
      was calculated with usual mathematical formulae. A radial artery cannula (n = 7),
      or a subclavian or femoral venous cannula (n = 14) was used to remove blood,
      which was collected within a bag containing CPC-adenine. Six % hydroxyethyl
      starch (Elohes) was given through a short venous cannula some distance from the
      first one. An antiparallel double line set in a roller pump was used to carry out
      the NH. A mean 1,341 +/- 405 ml of blood were withdrawn so as to reach a mean
      haematocrit of 30.6 +/- 2.4%. NH was completed within 17 +/- 6 min. No major
      haemodynamic changes occurred during the procedure. No significant differences
      were observed between expected and observed final haematocrits. There was no
      effect of the volume of blood withdrawn on the error of haematocrit prediction
      (0.5 +/- 0.3%). However, a higher rate of blood removal could increase this
      error. This easy-to-use device seems to provide fast and identical rates of blood
      removal and replacement. The expected haematocrit may thus be reached reliably,
      even if this must be checked for the sake of safety.

PMID- 7504426
TI  - Antenatal screening for Down's syndrome--can we do better?

PMID- 7504424
TI  - Transmission of hepatitis A to patients with hemophilia by factor VIII
      concentrates treated with organic solvent and detergent to inactivate viruses.
      The Italian Collaborative Group.
AB  - OBJECTIVE: To determine whether an outbreak of hepatitis A virus (HAV) infection
      that occurred in 52 patients with hemophilia in Italy was acquired through
      infusion of contaminated factor VIII or through environmental enteric
      transmission. DESIGN: A case-control study and a molecular analysis of HAV
      sequences from implicated lots of factor VIII and from infected patients.
      PATIENTS: The first 29 patients with hemophilia and jaundice in whom hepatitis A
      developed were compared with one to three matched controls with hemophilia but no
      jaundice. MEASUREMENTS: Type of concentrate and batches infused, number of doses,
      contacts with persons who had jaundice or hepatitis A, travel abroad to countries
      reported to have a high attack rate for hepatitis A, and consumption of raw
      shellfish. Hepatitis A viral sequences sought by polymerase chain reaction in
      lots of factor VIII and in serial serum samples from two patients with hemophilia
      in whom hepatitis A developed. Amplification by polymerase chain reaction of cDNA
      transcribed with reverse transcriptase from matched sets of factor VIII and
      recipient serum samples. Determination of nucleotide sequence of amplified
      hepatitis A virus genome. MAIN RESULTS: Case patients were neither more nor less
      likely than controls to have traveled to high-risk countries, consumed raw
      shellfish, or had contact with persons with jaundice. Case patients were more
      likely than controls to have received a factor VIII concentrate treated with a
      solvent-detergent mixture to inactivate viruses (odds ratio, infinity; 95% CI,
      4.5 to infinity) and to have had larger infusions of the concentrate during the
      presumed HAV incubation period (odds ratio, 8.54; CI, 2.78 to 27.5). Hepatitis A
      viral sequences were found in 5 of 12 tested lots of factor VIII. Genomic
      sequences of HAV obtained for two matched sets of factor VIII and recipient serum
      samples were identical within each set but different for the two sets.
      CONCLUSION: Hepatitis A was transmitted by a factor VIII concentrate treated by a
      virucidal method (solvent-detergent) that ineffectively inactivates nonenveloped
      viruses.

PMID- 7504425
TI  - Metastatic carcinoid disease presenting solely as high-output heart failure.

PMID- 7504427
TI  - Renal isoamylase clearance as a measure of altered renal charge selectivity in
      patients with diabetes mellitus.
AB  - Microalbuminuria is well established as a marker for early renal damage in
      diabetic patients. Differences in charge selectivity in glomerular protein
      filtration may also be an early marker of renal damage. We investigated the
      possible usefulness of the renal clearances of pancreatic and salivary amylases,
      and the ratio of the two, as markers of early renal damage in 55 diabetic
      subjects and 21 healthy controls. Diabetic patients with established albuminuria
      and microalbuminuria had increased clearance of salivary amylase and a trend
      toward lower pancreatic/salivary amylase clearance ratios compared to healthy
      controls and diabetic subjects without albuminuria, but the overlap with controls
      and diabetics without albuminuria was too large for the test to be useful.

PMID- 7504428
TI  - Use of free beta-hCG in Down's syndrome screening.

PMID- 7504429
TI  - Use of a simplified cell blot technique and 16S rRNA-directed probes for
      identification of common environmental isolates.
AB  - A simple technique in which rRNA-targeted oligodeoxynucleotide probes are used to
      identify bacteria immobilized on membranes is described. By using colony lifts,
      bacteria are directly transferred from plates to untreated nitrocellulose
      membranes. Alternatively, cells resuspended from colonies can be applied to
      membranes by using a vacuum manifold under high-salt conditions. Blotted cells
      are baked and hybridized under stringent conditions by using standard protocols.
      Treatment of blotted cells with sodium dodecyl sulfate, urea, formaldehyde, or
      protease had no apparent effect on hybridization signals. Hybridization to rRNA
      from cells that had been stored refrigerated for 6 days was readily detected;
      however, fivefold more cells (approximately 10(7) cells) were required to obtain
      hybridization signals comparable to those generated by cells not subjected to
      storage. The sequences of oligonucleotide probes specific for Pseudomonas
      cepacia, Comamonas testosteroni, and Acinetobacter calcoaceticus and a group
      probe identifying Pseudomonas aeruginosa, Pseudomonas mendocina, Pseudomonas
      fluorescens, Comamonas acidovorans, and "Flavobacterium" lutescens are presented.
      In conjunction with the colony lift hybridization procedure, bacteria isolated
      from river water were identified by using these probes.

PMID- 7504430
TI  - Isolation and characterization of an N-methylcarbamate insecticide-degrading
      methylotrophic bacterium.
AB  - A gram-negative bacterium which hydrolyzed aryl N-methylcarbamate insecticides
      was isolated from an agricultural soil which quickly degraded these pesticides.
      This organism, designated strain ER2, grew on carbofuran as a sole source of
      carbon and nitrogen with a doubling time of 3 h in a mineral salts medium. The
      aromatic nucleus of the molecule was not metabolized, and carbofuran 7-phenol
      accumulated as the end product of metabolism. The insecticides carbaryl,
      bendiocarb, and propoxur were similarly hydrolyzed, with each yielding the
      corresponding phenol. Strain ER2 contained two plasmids (120 and 130 kb). A probe
      cloned from the pDL11 plasmid of Achromobacter sp. strain WM111, which encodes
      the carbofuran hydrolase (mcd) gene (P. H. Tomasek and J. S. Karns, J. Bacteriol.
      171:4038-4044, 1989), hybridized to the 120-kb plasmid. Restriction fragment
      profiles of pDL11 and strain ER2 plasmid DNAs suggested that the 120-kb plasmid
      of strain ER2 is very similar to pDL11. On the basis of the results of
      biochemical tests, 16S rRNA sequence analysis, and membrane lipid analyses,
      strain ER2 was found to be a phylogenetically unique type II methylotroph. The
      constitutive carbofuran hydrolase activity in glucose-grown cells increased
      sevenfold when strain ER2 was grown in the presence of 100 mg of carbofuran per
      liter as the sole source of carbon and nitrogen or as the sole nitrogen source in
      the presence of glucose. Growth on carbofuran resulted in the induction of
      enzymes required for methylamine-dependent respiration and the serine pathway of
      formaldehyde assimilation. These results indicate that the carbofuran hydrolase
      mcd gene is conserved on a plasmid found in organisms from different geographic
      areas and that the specific activity of carbofuran degradation may increase in
      response to carbofuran treatment.

PMID- 7504431
TI  - Enumeration of Vibrio vulnificus on membrane filters with a fluorescently labeled
      oligonucleotide probe specific for kingdom-level 16S rRNA sequences.
AB  - Vibrio vulnificus was enumerated on membrane filters after hybridization with a
      fluorescent oligonucleotide eubacterial probe. Cells were hybridized in liquid
      buffer or directly on membrane filters. There was no significant difference
      between fluorescent oligonucleotide direct counts and acridine orange direct
      counts (P > 0.05). Liquid buffer hybridization was preferable to direct filter
      hybridization.

PMID- 7504432
TI  - Differentiation of Lactobacillus strains by ribotyping.
AB  - Fifty-four lactobacillus strains were differentiated by ribotyping. The stability
      of ribotypes characteristic of four strains of lactobacilli inhabiting the
      digestive tract of mice was investigated. One of four isolates of Lactobacillus
      delbrueckii GT21, which had been associated with mice for 22 months, had an
      altered ribotype.

PMID- 7504434
TI  - Mutations in the genes for epidermal keratins in epidermolysis bullosa and
      epidermolytic hyperkeratosis.
AB  - BACKGROUND: Clues from clinicopathologic studies of epidermolysis bullosa simplex
      (EBS) and epidermolytic hyperkeratosis (EH) have implicated abnormalities in
      keratin filaments as possibly underlying the pathogenesis of these diseases.
      Multiple avenues of study have now converged, which confirm this hypothesis.
      OBSERVATIONS: The clinical spectrum of EBS and EH is reviewed together with
      classic histologic, electron microscopic, and immuno-electron microscopic
      studies. Linkage analyses have shown in EBS and EH that the disease traits are
      linked to the keratin gene clusters on chromosomes 12 and 17. Transgenic mice
      bearing mutations or deletions in genes coding for basal cell keratin K14 express
      the phenotype of EBS, and transgenic mice bearing abnormal K1/K10 genes resemble
      EH. Increasing numbers of point mutations in the human keratin genes have been
      found in both sporadic and familial cases of EBS in keratins 5/14 and EH in
      keratins K1/K10 genes, respectively, particularly in highly conserved subdomains
      of the keratin proteins. CONCLUSIONS: The recent and rapid progress in
      understanding the molecular biology of EBS and EH will also enhance knowledge
      about intermediate filament structure and function. Further studies of the
      effects of these mutations on the control of keratinocyte growth and
      differentiation are required. They will lead the way to rational pharmacologic or
      gene therapy.

PMID- 7504433
TI  - Simple method of concentrating enteroviruses and hepatitis A virus from sewage
      and ocean water for rapid detection by reverse transcriptase-polymerase chain
      reaction.
AB  - A rapid and simple method was developed to detect enteroviruses and hepatitis A
      virus (HAV) in sewage and ocean water. Sewage samples were concentrated by
      Centriprep-100 and Centricon-100 at 1,000 x g. Samples collected from estuary and
      near-shore surf zone ocean water in Southern California were concentrated by
      vortex flow filtration and microconcentration. Reverse transcriptase-polymerase
      chain reaction (RT-PCR), with enterovirus primers or HAV capsid-specific primers,
      was used to detect enteroviruses or HAV in all concentrated samples. A
      nonradioactive internal probe was used to confirm the amplified products. Results
      of seeding experiments indicated that at 4 degrees C, HAV was more persistent
      than poliovirus in seawater and both HAV and poliovirus persisted longer at 4
      degrees C than at 25 degrees C. RT-PCR was at least 500-fold more sensitive than
      cell culture. Results were obtained within 5 h by RT-PCR, in contrast with the 5
      days to 3 weeks required for cell culture.

PMID- 7504435
TI  - Ultrastructural findings in epidermolysis bullosa.
AB  - BACKGROUND AND DESIGN: Electron microscopy of skin provides diagnostic criteria
      for distinguishing the simplex, junctional, and dystrophic forms of inherited
      epidermolysis bullosa (EB). The plane of cleavage in blister formation indicates
      the localization of structural weakness within the epidermis and basement
      membrane zone, and, together with ultrastructural changes in affected skin, these
      are clues to the underlying genetic bases for these disorders. Skin biopsy
      specimens from individuals with EB were evaluated by electron microscopy to
      identify structural changes and determine the subtype of EB. RESULTS: Discrete,
      circumscribed clumps of keratin filaments present in the basal keratinocytes are
      pathognomonic for EB simplex Dowling-Meara. These and other observations of
      keratin filament disruption have led to the identification of mutations in
      keratin genes in Dowling-Meara and Koebner forms of EB simplex. Changes in the
      density and structure of anchoring fibrils and the relative amount of type VII
      collagen detected by immunostaining of the dermoepidermal junction in dystrophic
      EB have led to sequencing of mutations in the type VII collagen gene. Although
      mutations in junctional EB have not been reported, findings of structural
      alterations in hemidesmosomes and immunohistochemical studies of kalinin (BM600
      and epiligrin), and in junctional EB with pyloric atresia alterations in the
      integrin alpha 6 beta 4, indicate molecules involved in basal keratinocyte
      adhesion to the basement membrane that are candidate genes for junctional EB.
      CONCLUSIONS: Electron microscopy of skin when correlated with mutations in EB
      will help us understand the significance of these structural molecules in normal
      skin and the pathogenesis of EB.

PMID- 7504436
TI  - Occurrence of antiperinuclear, antikeratin, and anti-RA 33 antibodies in juvenile
      chronic arthritis.
AB  - OBJECTIVES: Antiperinuclear factor (APF), antikeratin antibodies (AKA), and anti
      RA 33 antibodies are currently considered to be good markers for the diagnosis of
      adult rheumatoid arthritis with or without rheumatoid factor (RF). The prevalence
      of these markers was retrospectively reviewed in children with juvenile chronic
      arthritis (JCA) to determine whether they were associated with specific features.
      METHODS: One hundred and twenty-four patients with JCA participated in this
      study. Controls included 28 patients with juvenile systemic lupus erythematosus
      and 21 healthy children. Antiperinuclear factor and AKA were determined by
      indirect immunofluorescence on buccal mucosal cells and oesophagus sections
      respectively. Anti-RA 33 antibodies were detected using a Western blot technique
      on HeLa cell nuclear extract. RESULTS: Antiperinuclear factor was virtually
      absent in all the tested subgroups and anti-RA 33 antibodies were detected only
      in a subset of patients with RF positive polyarticular onset. Antikeratin
      antibodies were found in 27% of all children with JCA and in 42% of those with RF
      negative polyarticular onset. These results were statistically significant
      compared with healthy controls, but the presence of AKA was not specific to any
      patient subgroup. Moreover, in contrast with previous studies in adult RA, no
      relation was found between the presence of AKA and disease severity or activity.
      CONCLUSION: These data suggest that APF, AKA, and anti-RA 33 antibodies are not
      useful for the diagnosis or classification of JCA.

PMID- 7504437
TI  - Palisading cells of rheumatoid nodules: comparison with synovial intimal cells.
AB  - OBJECTIVES: The palisading cells of rheumatoid nodules share certain features
      with synovial intimal cells. The similarities between the two cell populations
      have been reassessed using new cytochemical markers. METHODS: Cell populations in
      cryostat sections of non-inflamed, rheumatoid and osteoarthritic synovial
      tissues, and rheumatoid nodules were assessed for the presence of CD68, prolyl
      hydroxylase, vascular cell adhesion molecule 1 (VCAM-1), and the alpha 4 and beta
      1 integrin chains, and the activity of uridine diphosphoglucose dehydrogenase
      (UDPGD) and nonspecific esterase. RESULTS: Synovial intimal cells formed a dual
      population of macrophages (nonspecific esterase positive, strongly positive for
      CD68) and fibroblastic cells (prolyl hydroxylase positive). The latter showed
      prominent VCAM-1 expression and high UDPGD activity as previously reported and
      also prominent beta 1 integrin chain expression. Palisading cells similarly
      proved to be a dual population of macrophages and fibroblastic cells. In contrast
      with synovial intima, however, the fibroblastic cells lacked UDPGD activity and
      expression of VCAM-1 and showed no preferential expression of the beta 1 integrin
      chain. The exception to this rule was where nodules contained central clefts,
      which were lined with cells showing all the features associated with synovial
      intimal cells. CONCLUSION: Palisading cells are a mixture of macrophages and
      fibroblasts, but the latter show no evidence of synoviocyte differentiation.
      Cells with features of synoviocytes may occur lining clefts within areas of
      necrobiosis.

PMID- 7504438
TI  - Vascular cell adhesion molecule 1 and alpha 4 and beta 1 integrins in lymphocyte
      aggregates in Sjogren's syndrome and rheumatoid arthritis.
AB  - OBJECTIVES: Interactions between vascular cell adhesion molecule 1 (VCAM-1) and
      its ligand, the alpha 4/beta 1 integrin, have been shown to be important in a
      number of cellular events in vitro. To assess the importance of such interactions
      in the development of lymphocytic infiltration in diseased tissue the
      distribution of the two ligands has been studied immunohistochemically. METHODS:
      Cryostat sections of labial tissue from patients with Sjogren's syndrome, normal
      labial tissues, rheumatoid synovia, and normal tonsils were stained using
      antibodies to VCAM-1, alpha 4 and beta 1 integrin chains, and markers for T
      cells, B cells, macrophages, and follicular dendritic reticulum cells (FDRCs),
      visualised using alkaline phosphatase and fast red. RESULTS: Staining patterns
      for VCAM-1 and integrin chains in lymphocyte aggregates in synovial and labial
      tissues were similar. VCAM-1 staining was found on both vascular and ramifying
      dendritic cells at the centre of large T cell aggregates and in all aggregates
      where there was a central clustering of B cells. VCAM-1 colocalised with, but
      also extended beyond, staining for the FDRC marker R4/23. Staining for the alpha
      4 and beta 1 integrin chains was more widespread than staining for VCAM-1, with
      no significant increase in staining at sites of maximum VCAM-1 staining. In
      tonsils VCAM-1 and R4/23 codistributed in germinal centres, but staining for the
      alpha 4 and beta 1 integrin chains was chiefly seen in T lymphocyte areas.
      CONCLUSIONS: VCAM-1 may be more important in determining the distribution of B
      than T lymphocytes in lymphocytic infiltration of non-lymphoid tissue. Unlike the
      follicles of lymphoid tissue, ectopic follicle-like structures in non-lymphoid
      tissues may form by immigration of B cells via VCAM-1+ vessels at the centre of T
      cell aggregates.

PMID- 7504439
TI  - Endothelin-1-induced oedema in rat and guinea-pig isolated perfused lungs.
AB  - Endothelin-1 caused an increase in perfusion pressure, bronchial resistance, lung
      weight and tracheal effusion when infused through the pulmonary artery of rat and
      guinea-pig isolated lungs. In contrast to vasoconstriction, the effects of
      endothelin-1 on bronchial resistance, lung weight and tracheal effusion were not
      concentration-dependent. Recovery from vasoconstriction occurred within 15-30 min
      when the lung was further perfused with Krebs buffer. Increases in lung weight,
      bronchial resistance and tracheal effusion induced by endothelin-1 were
      irreversible when infused at concentrations above 10(-10) M. UK 38,485, a
      thromboxane A2 synthesis inhibitor, partly prevented the increase in lung weight
      and tracheal effusion without altering the vasoconstriction induced by endothelin
      1. Such an antagonism was not seen in guinea-pig lung at the concentration used.
      Iloprost, a stable analogue of prostacyclin, antagonized the effects of
      endothelin-1 on perfusion pressure and lung weight without reducing tracheal
      effusion in both rat and guinea-pig lungs. Pretreatment with allopurinol did not
      alter the effects of endothelin-1. These results were taken as evidence for the
      potent lung oedema-producing effect of the peptide which seems to be partially
      mediated by the secondary release of thromboxane A2.

PMID- 7504440
TI  - Empiric long-term amiodarone prophylaxis following myocardial infarction. A meta
      analysis.
AB  - BACKGROUND: The prophylactic administration of amiodarone following acute
      myocardial infarction has been investigated in several small trials. This study
      combined the results of these small trials in a meta-analysis to determine the
      effects of prophylactic low-dose amiodarone on mortality following acute
      myocardial infarction. METHODS: Four prospective, randomized, placebo-controlled
      trials, which investigated the prophylactic administration of low-dose amiodarone
      (200 to 400 mg/d) to patients after acute myocardial infarction, were selected
      from the current literature according to strict inclusion criteria. A total of
      1140 patients, 566 in the amiodarone-treated group and 574 in the placebo-treated
      group, were included in the analysis. Sudden cardiac death, cardiac mortality,
      and total mortality were the end points of interest. In addition, the effect of
      impaired left ventricular function (ejection fraction, < 45%) on total mortality
      was assessed. Data were aggregated by using the Mantel-Haenszel method to obtain
      final summary statistics for these end points. RESULTS: Patients treated with low
      dose amiodarone exhibited a lower incidence of sudden cardia death (3.1%) and
      total mortality (6.1%) when compared with patients treated with placebo (6.9% and
      11.2%, respectively; both P < .01; and 95% confidence interval [CI], 0.011 to
      0.065 and 0.013 to 0.082, respectively). There was no significant difference
      between the amiodarone- and placebo-treated groups with respect to cardiac
      mortality (2.6% vs 3.7%, respectively; P = .26; and 95% CI, -0.012 to 0.032). For
      patients with a left ventricular ejection fraction of less than 45%, total
      mortality was 5.5% in the amiodarone-treated group and 9.4% in the placebo
      treated group (P = .30; CI, -0.023 to 0.101). CONCLUSIONS: Although further data
      from ongoing large, randomized trials are needed, this meta-analysis suggests
      that the prophylactic administration of low-dose amiodarone to patients following
      acute myocardial infarction reduces the incidence of both sudden cardiac death
      and total mortality. The benefits of low-dose amiodarone may be limited to
      patients with preserved left ventricular function.

PMID- 7504441
TI  - Tissue diagnosis of intestinal microsporidiosis using the chromotrope-2R modified
      trichrome stain.
AB  - Light microscopic diagnosis of intestinal microsporidiosis is difficult with the
      use of routine histologic stains. This has led to an overreliance on transmission
      electron microscopic diagnosis. It was previously demonstrated that a
      modification of the standard Gomori one-step trichrome stain, using a 10-fold
      higher concentration of chromotrope-2R, can be used to detect microsporidial
      spores in stool. The use of the stain has now been extended to the detection of
      spores in sections of formaldehyde-fixed, paraffin-embedded intestinal biopsy
      specimens. Positive identification can be made of both intestinal species seen in
      patients with the acquired immunodeficiency syndrome, Enterocytozoon bieneusi and
      Septata intestinalis, when the diagnosis is inapparent or questionable on routine
      histologic analysis. The use of this simple stain should increase the sensitivity
      for diagnosing microsporidiosis by light microscopy, further obviating the need
      for transmission electron microscopy.

PMID- 7504442
TI  - Human urinary trypsin inhibitor, urinastatin, prevents pancreatic injuries
      induced by pancreaticobiliary duct obstruction with cerulein stimulation and
      systemic hypotension in the rat.
AB  - OBJECTIVE: The protective effects of human urinary trypsin inhibitor against
      pancreatic injuries in multifactor-related experimental model of acute
      pancreatitis were evaluated. DESIGN: Experimental study. MATERIALS AND METHODS:
      Acute pancreatitis was induced by short-termed (1-hour) pancreatico-biliary duct
      obstruction with cerulein stimulation (30 minutes; 0.2 microgram/kg per hour) and
      systemic hypotension (30 minutes; 30% reduction of mean arterial pressure) in
      rats. In this model, the protective effects of UTI against pancreatic injuries
      were evaluated at a dose of 10,000 U/kg per hour. RESULTS: In this model,
      significant increases in portal serum amylase, cathepsin B and malate
      dehydrogenase levels were observed as compared with the control rats. The
      redistribution of cathepsin B from the lysosomal to the zymogen fraction and
      activation of trypsinogen were also observed. Moreover, the increased lysosomal
      and mitochondrial fragility as well as impaired pancreatic adenylate energy
      metabolism were noted. The therapeutic administration of human urinary trypsin
      inhibitor had significant protective effects against these pancreatic injuries.
      Furthermore, the combined prophylactic and therapeutic administration of human
      urinary trypsin inhibitor had more significant protective effects than only
      therapeutic treatment. CONCLUSIONS: These results suggest the importance of
      timing and of selecting a pertinent protease inhibitor, such as urinary trypsin
      inhibitor, in the treatment of pancreatitis.

PMID- 7504443
TI  - [Effect of indomethacin on the release of chemical mediators from human
      peripheral leukocytes].
AB  - We studied the effect of indomethacin (IND) on the release of chemical mediators
      from human peripheral leukocytes and the relation of prostaglandin (PG) E2 and
      PGI2 to that effect. We stimulated the leukocyte suspensions with calcium
      ionophore A23187 (CaI, 10(-6) M) accompanied with IND (10(-5) M), PGE2 (10(-5) M)
      or PGI2 (10(-5) M) and measured the levels in histamine (HA), leukotriene
      C4/D4/E4 (peptide-LTs) and LTB4 in the supernatant fluid. The increase of HA
      levels induced by CaI was significantly enhanced by IND (p < 0.01), and the
      enhancement was significantly inhibited by PGE2 (p < 0.05) and PGI2 (p < 0.01).
      The release of peptide-LTs was not enhanced by IND and was inhibited
      significantly by PGE2 (p < 0.05) and PGI2 (p < 0.01). IND did not affect the
      release of LTB4 induced by CaI. However, LTB4 release was also significantly
      inhibited by PGE2 and PGI2 (p < 0.01). These results suggest that the inhibitory
      effect of IND on the production of PGE2 and PGI2 results in the enhancement of HA
      release. PGE2 and PGI2 have a potent inhibitory effect on the release of HA,
      peptide-LTs and LTB4 from human leukocytes.

PMID- 7504444
TI  - [Analysis of ovalbumin-specific T cell lines established from patients with hen
      egg allergy].
AB  - Ten ovalbumin (OVA)-specific T cell lines (TCLs) were established from peripheral
      blood mononuclear cells of 6 patients with hen egg allergy, and the antigen
      recognition of these TCLs was characterized. Two OVA epitopes were determined by
      use of 3 synthetic OVA peptides which have been known as murine T cell epitopes.
      Blocking of antigen-specific T cell proliferation by anti-HLA class II monoclonal
      antibodies suggest that all 3 HLA class II molecules could act as restriction
      elements for T cell recognition of OVA. This is the first demonstration of OVA
      epitopes recognized by T cells in patients with hen egg allergy, as far as we
      know.

PMID- 7504445
TI  - [Clinical usefulness of histamine release test in determining allergens in food
      hypersensitivity].
AB  - We examined the clinical usefulness of three diagnostic tests including the
      histamine release test, RAST and prick test in determining which of a total of
      349 allergens were responsible for individual cases of food hypersensitivity. The
      subjects were 42 children (mean 3.3 years old). When compared with the results of
      the offending allergen confirmed by elimination and provocation test, each
      diagnostic test showed a fairly good correlation in percentage agreement and
      negative agreement, but there was poor correlation in positive agreement
      (histamine release test 58.1%, RAST 62.8%, prick test 48.8%). False positive
      results were more frequently observed in RAST (12.6%) as compared with the
      histamine release test (4.0%) and prick test (2.3%). McNemar's analysis
      demonstrated that the histamine release test, but not RAST or the prick test, was
      matched the diagnosis by elimination and provocation test (alpha = 0.30). These
      results suggest that the histamine release test is more clinically useful than
      RAST or the prick test in the diagnosis of food hypersensitivity.

PMID- 7504446
TI  - The adjuvant activity of pyrene in diesel exhaust on IgE antibody production in
      mice.
AB  - In this communication, it is shown that pyrene has an adjuvant activity on IgE
      antibody production when mice are immunized by an intraperitoneal injection of
      ovalbumin (OA) or Japanese cedar pollen allergen (JCPA) with pyrene. The effects
      of pyrene on IgE antibody production in mice were investigated to clarify the
      relation between pollen allergy and the adjuvanticity of the chemical compounds
      contained in diesel-exhaust particulates (DEP). In the first experiment, three
      groups of mice were immunized intraperitoneally six times at 2-week intervals
      with 1 microgram of OA alone, 1 microgram of OA plus 1 mg of pyrene, and 1
      microgram of OA plus 1 mg of DEP, respectively. The IgE antibody responses to OA
      in mice immunized with OA plus pyrene or OA plus DEP were extremely enhanced as
      compared with those in mice immunized with OA alone, and the highest responses
      were observed in mice immunized with OA plus DEP. In the second experiment, mice
      were immunized with 10 micrograms of JCPA alone or 10 micrograms of JCPA plus 5
      mg of pyrene in the same way. The IgE antibody responses to JCPA in mice
      immunized with JCPA plus pyrene were higher than those in mice immunized with
      JCPA alone. The intraperitoneal macrophages of the mice also clearly stimulated
      in vitro by pyrene on chemiluminescence assay. These results suggest that pyrene
      contained in DEP acts as an adjuvant in IgE antibody production when mice are
      immunized with antigens.

PMID- 7504447
TI  - Heterogeneity of the endothelial cell.

PMID- 7504448
TI  - Regulation of leukocyte migration by L-selectin: mechanisms, domains and ligands.

PMID- 7504449
TI  - The possible role of membrane complement regulators in vasculitis.
AB  - Potentially, damage to endothelial cells of small vessel walls may be induced by
      the deposition of immune complexes and subsequent complement activation. The
      degree of deposition of C3b onto the endothelial cell surface under normal
      conditions is regulated by a number of membrane-bound regulators. Under
      inflammatory conditions various cytokines could potentially deregulate the
      expression and function of the membrane-bound complement inhibitors. Such a
      process could potentially increase the susceptibility of the endothelial cell
      layer to complement-mediated attack and provoke a vascular lesion.

PMID- 7504451
TI  - Role of the macrophage in the positive and negative regulation of wound
      neovascularization.

PMID- 7504450
TI  - The contact allergens nickel chloride and cobalt chloride directly induce
      expression of endothelial adhesion molecules.
AB  - Activation of vascular endothelium is a key event in the initial phase of an
      inflammatory reaction e.g. to contact allergens. In the present study the effect
      of two common contact sensitizers, NiCl2 and CoCl2, on endothelial expression of
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin) was
      studied. NiCl2 and CoCl2 were found to upregulate these adhesion molecules on
      human umbilical vein endothelial cells (HUVEC) in a dose- and time-dependent
      manner as could be demonstrated by flow cytometry and enzyme-linked immunosorbent
      assay. During organ culture of foreskin samples treatment with NiCl2 led to
      upregulation of ELAM-1 and ICAM-1 but not VCAM-1 on microvascular endothelium.
      Induction of adhesion molecules by NiCl2 was found to depend on de novo mRNA and
      protein synthesis and could be blocked by the protein kinase inhibitor H-7 in a
      dose-dependent manner but not by HA-1004 and staurosporine. An autocrine IL-1
      dependent mechanism mediating NiCl2 effects could be excluded. Our data
      demonstrate that allergens as NiCl2 and CoCl2 are capable of directly activating
      endothelium which is an important step in evolving inflammatory reactions and may
      thus be of relevance for the pathogenesis of contact hypersensitivity.

PMID- 7504452
TI  - P-selectin and wound healing.
AB  - The history of the wound can by some accounts be traced nearly 5,000,000 years in
      the prehistoric ancestry of man (Majno, 1991). While there have been many
      descriptive accounts of the wound and wound healing over the centuries, in recent
      years rapid advances in the field of adhesion biology have added greatly to the
      understanding of the wound. Disruptions in the continuity of the vessel wall,
      whether by trauma or disease, induce a number of physiologic responses. The
      endothelium responds to fibrin contact in numerous ways including the rapid
      release of stored of von Willebrand factor and the expression of P-selectin upon
      the cell surface. Deposition of fibrin at the site of vascular injury serves
      other vital roles in the acute response to injury. Fibrin deposition stabilizes
      platelets as part of the development of a mural thrombus. Fibrin may also act to
      serve as a biological scaffold upon which inflammatory cells may adhere and
      participate in the acute response to injury. Finally, it is apparent that fibrin
      may act as a lattice upon which fibroblasts, smooth muscle cells and endothelial
      cells may adhere and migrate in order to return the vessel to its original state.
      In tumorigenesis, fibrinogen and fibrin may deposit in the perivascular space
      within the tumor and contribute by incompletely understood mechanisms to tumor
      growth and metastasis. The understanding of fibrin induced endothelial cell
      responses and how P-selectin and other endothelial cell adhesion molecules
      function in wound healing is important for understanding the vascular response to
      injury.

PMID- 7504454
TI  - CD44 splice variants: expression during lymphocyte activation and tumor
      progression.
AB  - A recently described splice variant of CD44 has been shown to confer metastatic
      potential to non-metastasizing rat pancreatic carcinoma and sarcoma cell lines.
      Using antibodies raised against a bacterial fusion protein encoded by variant
      CD44 sequences, we have explored the expression of variant CD44 glycoproteins in
      human lymphoid cells and tissues, in non-Hodgkin's lymphomas, and in colorectal
      neoplasia. Normal lymphohematopoietic cells express barely detectable low levels
      of variant CD44 glycoproteins, while T lymphocytes, upon activation by mitogen or
      antigen, transiently upregulate expression of specific CD44 variant
      glycoproteins. The reaction pattern of various antibodies indicates that these
      CD44 variants contain the domain encoded by exon v6, which is part of the variant
      that in the rat confers metastatic capability. Interestingly, overexpression of
      v6 was also found in several aggressive, but not in low-grade, non-Hodgkin's
      lymphomas (NHL). In human colorectal neoplasia we also observed strong
      overexpression of CD44 splice variants in all invasive carcinomas and carcinoma
      metastasis. Interestingly, focal expression was already observed in adenomatous
      polyps, expression being related to areas of dysplasia. The findings establish
      CD44 variants as tumor progression markers in colorectal cancer.

PMID- 7504453
TI  - Angiogenesis in wound healing and tumor metastasis.
AB  - Formation of new blood vessels is essential for several physiological and
      pathological events, e.g. embryogenesis, wound healing and tumor growth and
      metastasis. In order to increase the insight into the mechanisms of angiogenesis
      we have visualized the different components of the microvasculature in human
      wounds and tumors by immunohistochemistry on the light and electronmicroscopic
      level. For this purpose, antibodies recognizing distinct markers for human
      endothelial cells, pericytes and basal lamina were used on freshly frozen or
      paraformaldehyde-fixed tissue samples. In terms of efficacy, the PAL-E antigen is
      highly specific for blood vessel endothelium. Its sensitivity is less than other
      endothelial markers, such as von Willebrand factor and CD 31, as it is not
      expressed in arterioles. Within the context of the microvasculature alpha-smooth
      muscle actin and the HMW-MAA chondroitin sulphate proteoglycan are useful markers
      for pericytes. Type IV Collagen and Laminin can be visualized consistently in the
      microvascular basal lamina. During the formation of granulation tissue in wound
      healing a heterogeneity of the expression of endothelial and pericyte markers is
      found. In the least matured zone in granulation tissue of decubitus lesions and
      experimental skin wounds microvessels already contained both endothelial cells
      and pericytes, suggesting a role for both cell types in the early steps of
      angiogenesis. Regarding the tumor microvasculature, antibodies to von Willebrand
      factor often failed to stain capillaries, that did show expression of the other
      endothelial markers studied. Broad staining in pericytes was found for the HMW
      MAA chondroitin sulphate proteoglycan. In contrast, these cells only locally
      expressed alpha-smooth muscle actin. Staining of the basal lamina components Type
      IV Collagen and Laminin within tumors was not restricted to the microvasculature.
      Therefore, antibodies recognizing endothelial markers, particularly PAL-E and BMA
      120, are preferable as tools to visualize the tumor microvasculature. In
      accordance with the situation in granulation tissue of wound healing the broad
      presence of pericytes in the microvasculature of human tumor suggests an
      involvement of this cell type in tumor angiogenesis. Recent immunohistochemical
      studies on human tumor lesions indicated that a high number of microvessels
      adjacent to the tumor as a measure of tumor angiogenesis is an unfavorable
      prognostic factor in cutaneous melanoma, mammary carcinoma and non-small cell
      pulmonary carcinoma. This new application of immunohistochemistry represents a
      valuable, clinically relevant adjunct to the repertoire of the surgical
      pathologist.

PMID- 7504455
TI  - Integrins and L-selectin in lymphocyte-endothelium interactions and homing into
      gut-associated tissue.
AB  - The selective entry of subpopulations and distinct differentiation stages of
      lymphocytes into different tissues is thought to be mediated by interaction of
      endothelial ligands with adhesion molecules on lymphocytes. L-selectin has been
      considered as a peripheral lymph node-specific homing receptor and alpha 4
      integrins have been supposed to mediate entry into mucosa-associated lymphoid
      tissue. In vivo homing studies show that the specificity is not so clear-cut. The
      MEL-14 antibody indeed blocks almost completely lymphocyte homing into peripheral
      lymph nodes. However, entry into Peyer's patches and even the intestine itself is
      also affected. Thus, L-selectin plays a broader part as previously thought. Some
      antibodies against the alpha 4 and beta 1-integrin chain inhibit selectively
      lymphocyte homing to Peyer's patches by 50-70%. alpha 4-integrins therefore seem
      to be important for homing into mucosa-associated tissue, although a considerable
      fraction of cells does not require this molecule (or this epitope) for
      recognition of Peyer's patch endothelium. In vitro and in vivo data indicate that
      neither VCAM-1 nor fibronectin play a role for homing into Peyer's patches; most
      likely a further ligand recognized by distinct epitopes of alpha 4 is used for
      recognition of Peyer's patch HEV. A combination of the mAbs MEL-14 and PS/2.3
      blocks nearly completely the localization in Peyer's patches. Beside alpha 4
      integrins, the beta 2-integrin LFA-1 has been shown to be involved in lymphocyte
      recirculation. Also combinations of antibodies against LFA-1 and L-selectin as
      well as of anti LFA-1 with anti alpha 4 show synergistic effects.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7504456
TI  - Involvement of LFA-1/ICAM and CD2/LFA-3 in human endothelial cell accessory
      function.
AB  - Interactions of endothelial cells with T cells occur during the process of
      lymphocyte migration and during leukocyte extravasation in the course of an
      inflammatory response. Adhesion molecules are crucially involved in these
      interactions. It has been assumed that, in this way, endothelial cells play an
      important role in the recruitment of immune cells to sites of inflammation. In
      vitro experiments indicate that, in addition to this function in leukocyte
      recirculation, endothelial cells might also be involved as accessory cells in the
      stimulation of T cells. In this overview, the possible role of adhesion molecules
      in this process will be discussed.

PMID- 7504457
TI  - Dual phosphorylation and autophosphorylation in mitogen-activated protein (MAP)
      kinase activation.
AB  - p42mapk [mitogen activated protein (MAP) kinase; extracellular signal-regulated
      protein kinase (ERK)] is a serine/threonine-specific protein kinase that is
      activated by dual tyrosine and threonine phosphorylation in response to diverse
      agonists. Both the tyrosine and threonine phosphorylations are necessary for full
      enzymic activity. A MAP kinase activator recently purified and cloned has been
      shown to be a protein kinase (MAP kinase kinase) that is able to induce the dual
      phosphorylation of MAP kinase on both the regulatory tyrosine and threonine sites
      in vitro. In the present paper we have utilized MAP kinase mutants altered in the
      sites of regulatory phosphorylation to show, both in vivo and in vitro, that
      phosphorylation of the tyrosine and the threonine can occur independently of one
      another, with no required order of phosphorylation. We also utilized kinase
      defective variants of MAP kinase with mutations in either the ATP-binding loop or
      the catalytic loop, and obtained data suggesting that the activity or structure
      of the catalytic loop of MAP kinase plays an important role in its own dual
      phosphorylation.

PMID- 7504458
TI  - Modulation by fatty acids of Ca2+ fluxes in sarcoplasmic-reticulum vesicles.
AB  - The fatty acids palmitic (C16:0), stearic (C18:0), arachidic (C20:0) and
      arachidonic (C20:4) acids inhibit Ca2+ uptake and enhance Ca2+ efflux measured in
      vesicles derived from the sarcoplasmic reticulum of skeletal muscle. These
      effects of the fatty acids are impaired by the Ca(2+)-ATPase ligands Mg2+, Ca2+
      and K+, and by drugs that block the leakage of Ca2+ through the Ca(2+)-ATPase
      such as Ruthenium Red, spermine [de Meis (1991) J. Biol. Chem. 266, 5736-5742]
      and thapsigargin [de Meis and Inesi (1992) FEBS Lett. 299, 33-35].

PMID- 7504459
TI  - Induction of germ-cell alkaline phosphatase by butyrate and cyclic AMP in BeWo
      choriocarcinoma cells.
AB  - BeWo choriocarcinoma cells synthesize two alkaline phosphatase isoenzymes: germ
      cell alkaline phosphatase and tissue-unspecific alkaline phosphatase. We have
      made use of the differential heat-stabilities of these two isoenzymes to study
      the induction of germ-cell alkaline phosphatase by sodium butyrate and cyclic AMP
      (cAMP). Sodium butyrate causes a large induction of germ-cell alkaline
      phosphatase activity (approx. 35-fold after 96 h) after an initial lag period of
      12-24 h. We showed that butyrate increases germ-cell alkaline phosphatase mRNA.
      Dibutyryl cAMP also induces germ cell alkaline phosphatase (approx. 2.5-fold
      after 96 h). When optimal concentrations of butyrate and dibutyryl cAMP were
      added simultaneously to cells, they caused a synergistic induction of activity.
      This suggested that these compounds use separate mechanisms to induce germ-cell
      alkaline phosphatase activity and that it is the cAMP moiety of dibutyryl cAMP
      that induces enzyme activity. This was confirmed by the use of two additional
      cAMP analogues, 8-(4-chlorophenylthio) cAMP and 8-bromo cAMP, and of two
      compounds, 3-methyl-1-isobutylxanthine and cholera toxin, which raise the
      endogenous concentration of cAMP. All four compounds caused a 2-fold increase in
      enzyme activity. Treatment of cells with 8-(4-chlorophenylthio) cAMP, 8-bromo
      cAMP and cholera toxin increased germ-cell alkaline phosphatase mRNA between 2-
      and 7-fold. These data suggest that this alkaline phosphatase isoenzyme is
      regulated at the level of its mRNA by cAMP, in a manner distinct from that of
      butyrate.

PMID- 7504461
TI  - Transformation of NIH3T3 cells with ras oncogenes abrogates the retinoic acid
      induction of tissue transglutaminase.
AB  - Retinoic acid greatly increases enzyme activity and mRNA expression of the tissue
      type transglutaminase enzyme in NIH3T3 cells. This response is blocked in cells
      transformed with activated H-ras, K-ras or N-ras oncogenes, but not in pSVneo
      vector transfected cells. Lack of induction by RA of the tissue-type TGase in
      these ras-transformed fibroblasts suggests intersecting pathways between retinoid
      action and the ras oncogene.

PMID- 7504460
TI  - Developmentally regulated transcription of the four liver-specific genes for
      inter-alpha-inhibitor family in mouse.
AB  - The inter-alpha-inhibitor family is composed of the plasma-protease inhibitors
      inter-alpha-inhibitor, pre-alpha-inhibitor and bikunin. Inter-alpha-inhibitor and
      pre-alpha-inhibitor are distinct assemblies of bikunin with distinct sets from
      three heavy (H) chains designated H1, H2 and H3. These H chains are encoded by a
      set of three evolutionarily related H genes, and bikunin by an alpha-1
      microglobulin/bikunin precursor gene (AMBP). This precursor is cleaved to yield
      bikunin, a member of the Kunitz-type protease-inhibitor superfamily, and alpha-1
      microglobulin, which belongs to the lipocalin superfamily. Northern-blot
      experiments with RNAs obtained from various tissues in fetal and in adult mice
      indicated that the transcription of the four AMBP and H genes is liver
      restricted, although there is expression of H3 in brain. An analysis of the H1,
      H2, H3 and AMBP transcripts, as well as of transcripts for other control genes,
      in liver during development showed a progressive increase in the amounts of the
      H1, H2, H3 and AMBP RNAs, which all peak transiently at day 5 after birth. This
      was shown by a nuclear run-on experiment to originate from a change in
      transcription rate. The transient and postnatal increase in transcription could
      be explained neither by the liver-restricted expression nor by a common origin of
      these four genes, nor by a perinatal requirement for many lipocalins or protease
      inhibitors. This suggests that all four genes are perinatally triggered at the
      level of similar elements in their transcriptional regulatory regions, a
      conclusion strengthened by the weak expression of the four genes that is seen in
      a mutant mouse strain (albino) that is deficient in some liver-specific
      transcription factors.

PMID- 7504463
TI  - Molecular cloning of the testicular follicle stimulating hormone receptor of the
      non human primate Macaca fascicularis and identification of multiple transcripts
      in the testis.
AB  - Reverse transcription PCR was used to amplify the complete open reading frame of
      the follicle-stimulating hormone receptor (FSHR) from testicular poly (A)+ RNA of
      the non-human primate Macaca fascicularis. Along with the structural motifs of a
      G-protein coupled receptor, sequence analysis reveals that the monkey FSHR is
      highly homologous to the human FSHR and has specific features such as N-linked
      glycosylation sites which are identical to the human FSHR but not present in the
      rat or ovine FSHR. Northern blot hybridization of testicular poly (A)+ RNA to a
      cRNA probe corresponding to the extracellular domain of the monkey FSHR resulted
      in the identification of several transcripts, indicating alternative splicing
      events of the primary transcript.

PMID- 7504464
TI  - Purification, characterization and N-terminal amino acid sequence of a new major
      allergen from European chestnut pollen--Cas s 1.
AB  - Pollens from trees of the order Fagales (e.g. birch, alder, hazel, and hornbeam)
      all contain one major allergen--the main cause for tree pollen allergy. So far
      the major allergens from birch (Bet v 1), alder (Aln g 1), hazel (Cor a 1), and
      hornbeam (Car b 1) have been characterized, showing high sequence similarity with
      each other (1-4). We present the molecular and immunologic characterization of
      Cas s 1, the major allergen from the European chestnut (Castanea sativa). From
      aqueous pollen extracts from European chestnut a protein was purified to
      homogeneity and was subjected to further investigation. The protein revealed a Mr
      of 22 kDa and was shown to represent the major allergen of the European chestnut
      (immunoblotting, histamine release) and designated Cas s 1. Despite a marked
      difference in Mr, Cas s 1 shows significant amino acid sequence similarity at the
      N-terminus and is antigenically closely related to the major birch pollen
      allergen Bet v 1 (17 kDa), as shown by binding to the anti-Bet v 1 monoclonal
      antibody BIP-1 and by IgE-inhibition tests using recombinant Bet v 1.

PMID- 7504462
TI  - The fatty acid binding site of human alpha-fetoprotein.
AB  - alpha-Fetoprotein (AFP) binds a series of endogenous fatty acids. To identify the
      fatty acid binding site, this protein, purified from umbilical cord blood by
      immunoaffinity chromatography, was covalently labeled using 12-(9-anthroyloxy)
      stearic acid conjugated with Woodward's reagent K. After digestion with lysyl
      endopeptidase, the fatty acid-labeled peptide was isolated. Amino acid sequence
      analysis showed that this peptide consisted of the amino acid residue 210-227.
      The fact that no appreciable PTH-amino acid was detected at 14th cycle on the
      degradation suggested that Lys223 was modified with the fatty acid. The finding
      that lysyl endopeptidase did not cleave off at the Lys223 supported this
      suggestion. These results indicate that the carboxyl group of the bound fatty
      acid is located close to Lys223 in human AFP.

PMID- 7504465
TI  - Protein kinase regulation of tumor necrosis factor alpha stimulated collagenase
      and stromelysin message levels in chondrocytes.
AB  - TNF stimulated transcription and secretion of the metalloproteinases collagenase
      and stromelysin in porcine articular chondrocytes. TNF induced metalloproteinase
      transcription could be inhibited with either protein kinase inhibitors (H7 or
      staurosporine) or by raising intracellular cAMP levels. HA1004, a protein kinase
      inhibitor structurally related to H7 but with a higher Ki for protein kinase C
      had no effect on TNF induced message levels. TNF treatment of chondrocytes did
      not induce membrane associated PKC or increase intracellular cAMP levels. Our
      results are consistent with the involvement of a staurosporine and H7 sensitive
      protein kinase distinct from PKC in TNF signal transduction in chondrocytes.

PMID- 7504466
TI  - Preliminary molecular analysis of a case of feline mucopolysaccharidosis VI.
AB  - Deficiency of the lysosomal enzyme arylsulphatase B (ASB) causes, in man, the
      Maroteaux-Lamy disease (mucopolysaccharidosis type VI, MPS VI). MPS VI has been
      described also in Siamese cats. Isolation and characterization of the human and
      feline cDNAs encoding ASB has been reported as well as the assignment of the
      feline ASB gene to feline chromosome A1. The present paper describes the Southern
      and Northern blot analyses on DNA and RNA from an MPS VI affected cat using the
      human arylsulphatase B probe (ASB2). Our data suggest that a gross
      deletion/rearrangement of the ASB gene is present in the affected animal.

PMID- 7504467
TI  - Beta 1 integrin-mediated T cell adhesion is regulated by calcium ionophores and
      endoplasmic reticulum Ca(2+)-ATPase inhibitors.
AB  - Treatment of T lymphoblasts with stimuli that mobilize [Ca2+]i, such as
      ionophores (ionomycin and A23187) and endoplasmic reticulum Ca(2+)-ATPase
      inhibitors (thapsigargin, 2,5-di-(tert.-butyl)-hydroquinone and cyclopiazonic
      acid), activated T cell binding to extracellular matrix (ECM) proteins. T
      lymphoblast adhesion to ECM proteins stimulated by ionomycin, thapsigargin, or
      PMA was inhibited by an anti-beta 1 integrin mAb (4B4), confirming the role of
      beta 1 integrins in regulated T cell-ECM interactions. Study of the alpha
      integrin subunit specificity of activated lymphoblast-fibronectin interactions
      demonstrated that alpha 5 beta 1 was the major integrin receptor regulating
      binding to fibronectin. These results indicate that intracellular Ca2+
      mobilization plays a major contributory role in the activation of T cell beta 1
      integrins.

PMID- 7504468
TI  - Direct trophic effects of fibroblast growth factors on rat pancreatic acinar
      cells in vitro.
AB  - We examined the effects of fibroblast growth factors (FGFs) on rat pancreatic
      acinar cells in primary culture. Both basic and acidic FGF stimulated
      [3H]thymidine incorporation in a dose-dependent fashion. Maximum effects of 6-7
      fold over control were seen with 1 nM bFGF or 100 nM aFGF. These data indicate
      that FGFs are potent stimulants of rat pancreatic acinar cell DNA synthesis.
      Therefore, FGFs may play an important role in long term regulation of the
      exocrine pancreas in vivo. We also examined the interaction of bFGF with the
      pancreatic secretogogues CCK and carbachol. Effects of CCK, which is itself an
      acinar cell trophic factor, were additive with those of bFGF. In contrast,
      carbachol, which has no growth stimulatory effect, did not affect bFGF mediated
      stimulation of DNA synthesis. These data suggest that the mechanisms involved in
      acinar cell growth regulation are independent from those involved in secretion.

PMID- 7504469
TI  - Lipopolysaccharide treatment in vivo induces widespread tissue expression of
      inducible nitric oxide synthase mRNA.
AB  - Nitric oxide (NO) may mediate the hypotension of septic shock, but the effect of
      endotoxin on inducible NO synthase (iNOS) mRNA expression remains unclear. We
      studied the effects of lipopolysaccharide (LPS) treatment in vivo on iNOS mRNA
      expression using reverse transcription and polymerase chain reaction. The iNOS
      mRNA was absent or negligible in any tissue studied from control rats, but was
      markedly increased in lung, liver, spleen, skeletal muscle and kidney from LPS
      treated rats. The LPS-induced increase in iNOS mRNA was prevented by
      dexamethasone. Our results indicate that LPS treatment in vivo induces the
      expression of an iNOS mRNA via a dexamethasone-sensitive mechanism, and thus
      provide direct molecular evidence for the involvement of NO in septic shock.

PMID- 7504470
TI  - Characterization of cDNA for a dehydration-inducible gene that encodes a CLP A, B
      like protein in Arabidopsis thaliana L.
AB  - Sequence was obtained from a cDNA clone, designated ERD1, isolated from a cDNA
      library of 1-hour-dehydrated plants of Arabidopsis thaliana L. The clone (3150
      bp) contains an open reading frame of 946 amino acid residues with greater than
      34% sequence identity to the regulatory subunit of the Clp ATP-dependent protease
      in Escherichia coli and contains a putative chloroplast-targeting signal at the N
      terminus. Southern blot analysis suggested the presence of additional ERD1
      related genes in A. thaliana. The expression of ERD1 gene was strongly induced by
      dehydration-stress but not by heat-, cold-, or heavy-metal-stress. In addition
      ERD1 gene-expression was not strongly affected by treatment with plant growth
      regulators, such as auxin, cytokinin, abscisic acid, and gibberellic acid, or by
      starvation-stress for 10 hours.

PMID- 7504471
TI  - Activation of the cdc25C phosphatase in mitotic HeLa cells.
AB  - The cdc2-activator cdc25C was immunoprecipitated from HeLa cell extracts and
      assayed as tyrosine phosphatase (PTP) using tyrosine-phosphorylated myelin basic
      protein. The PTP activity was 12-fold higher in immunocomplexes from mitotic
      (nocodazole-arrested) than from asynchronous cells. This difference is due to
      enzyme activation, since the same amount of cdc25C was immunodetected in both
      conditions. However, mitotic cdc25C had M(r) 59,000, while a 56,000-59,000
      doublet was detected in immunocomplexes from asynchronous cells. The PTP activity
      of mitotic cdc25C was decreased by treatment with Phosphatase-2A catalytic
      subunit (but not with Phosphatase-1), with re-appearance of the 56,000
      polypeptide. cdc25C was also found associated with cdc2-p13-Sepharose complex and
      its PTP activity was 7-fold higher in samples from mitotic than from asynchronous
      cells. cdc25C and cdc2 co-migrated during gel filtration and the higher activity
      of mitotic cdc25C was retained through gel filtration.

PMID- 7504473
TI  - Altered ligand specificity of proteolysed insulin-like growth factor binding
      protein-3.
AB  - IGF binding protein-3 (IGFBP-3) undergoes limited proteolysis in human pregnancy
      serum, altering its electrophoretic mobility and its binding of radioiodinated
      IGF tracers. IGF-I tracer, monoiodinated on Tyr31, discriminated less than other
      tracers between intact and proteolysed IGFBP-3. In competitive binding curves
      using this tracer, intact IGFBP-3 showed comparable reactivity towards IGF-I and
      analogs with substitutions at Tyr24, Tyr31 or Tyr60. In contrast, proteolysed
      IGFBP-3 reacted equally with IGF-I and [Ala31]IGF-I (approximately 10-fold lower
      potency than with intact IGFBP-3), but showed a marked selectivity against
      [Ser24]IGF-I and [Leu60]IGF-I (approximately 100-fold lower potency than with
      intact IGFBP-3). The affinity of IGF-I binding to proteolysed, but not intact,
      IGFBP-3 was increased by the addition of the acid-labile subunit of the IGFBP-3
      complex. This study defines more fully the lesion in IGFBP-3 caused by serum
      proteolysis during pregnancy and demonstrates that tyrosine-substituted IGF-I
      derivatives are valuable tools in studying IGFBP-3 proteolysis.

PMID- 7504472
TI  - Growth factor regulation of interleukin-1 beta-induced nitric oxide synthase and
      GTP: cyclohydrolase expression in cultured smooth muscle cells.
AB  - Induction of NO synthase expression by interleukin-1 beta in cultured vascular
      smooth muscle cells from rat aortas was accompanied by simultaneous induction of
      GTP: cyclohydrolase I. This enzyme regulates the de novo synthesis pathway for
      tetrahydrobiopterin, an essential cofactor for the catalytic conversion of L
      arginine to L-citrulline and NO by inducible NO synthase. Inhibition of GTP:
      cyclohydrolase attenuated NO production by interleukin-1 beta-stimulated smooth
      muscle cells. Peptide growth factors such as fibroblast growth factor, platelet
      derived growth factor and transforming growth factor beta 1 and the protease
      thrombin have been shown to modulate the production NO by cytokine-treated smooth
      muscle cells. These peptide agonists also regulated the induction of NO synthase
      and GTP: cyclohydrolase mRNA expression.

PMID- 7504474
TI  - Angiotensin II mediates intracellular signalling in vascular smooth muscle cells
      by activation of tyrosine-specific protein kinases and c-raf-1.
AB  - Angiotensin II induces protein tyrosine kinase activation and apparent decreased
      electrophoretic mobility of the c-raf-1 serine/threonine protein kinase in
      cultured rat vascular smooth muscle cells. Tyrosine phosphorylation of at least 9
      cellular proteins with molecular weights of 151, 131, 116, 110, 90, 65, 62, 60,
      52 kd was induced in a time- and concentration-dependent manner, and included a
      serine/threonine protein kinase. The phosphotyrosine containing proteins differed
      from those induced by PDGF BB or AB. Angiotensin II by itself was shown not to
      act as a mitogen in cultured smooth muscle cells.

PMID- 7504475
TI  - O-antigenic lipopolysaccharide of Vibrio cholerae O139 Bengal, a new epidemic
      strain for recent cholera in the Indian subcontinent.
AB  - Lipopolysaccharide (LPS) from Vibrio cholerae O139 Bengal contained colitose (3,6
      dideoxy-L-galactose) in addition to glucose, L-glycero-D-manno-heptose, fructose,
      glucosamine and quinovosamine in its polysaccharide and only glucosamine in lipid
      A, while perosamine, a characteristic component sugar of V. cholerae O1 LPS, was
      absent. 3-Hydroxydodecanoic, tetradecanoic and hexadecanoic acids as ester-bound
      fatty acids and 3-hydroxytetradecanoic acid as amide-bound fatty acid were
      identified in the lipid A. A very high serological specificity of O139 LPS
      distinct from that of O1 V. cholerae was demonstrated by passive hemolysis and
      passive hemolysis inhibition tests by using the LPS either as antigen for
      sensitizing sheep red blood cells or as inhibitor in the latter test.

PMID- 7504476
TI  - Differential expression of iNOS and cNOS mRNA in human vascular smooth muscle
      cells and endothelial cells under normal and inflammatory conditions.
AB  - To examine the potential contribution of endothelial cell cNOS (ec-cNOS) and
      inducible NOS (iNOS) in controlling vascular tone under normal versus
      inflammatory conditions, we performed Northern hybridizations to examine the
      differential expression of each NOS mRNA in human aortic endothelial cells (AOEC)
      and human aortic smooth muscle cells (AOSMC) cultured for 8 h in the presence or
      absence of cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) and LPS. Cytokine/LPS
      treatment induced a 4.4 kb iNOS mRNA in the human AOSMC; in contrast,
      cytokine/LPS treatment down regulated the expression of ec-cNOS mRNA in the AOEC.
      No iNOS mRNA was detected in the AOEC under the conditions examined. These
      results suggest that under specific inflammatory conditions the generation of NO
      in vascular tissue switches from ec-cNOS in the endothelium to iNOS in the smooth
      muscle.

PMID- 7504477
TI  - The effect of ethanol and extracellular matrix on induction of p36 protein kinase
      substrate expression in rat hepatocytes.
AB  - p36 plays a direct role in DNA synthesis and is overexpressed in transformed
      cells. It is also an important component linking the cell membrane to
      intracellular cytoskeletal components. Experiments were performed in primary rat
      hepatocyte culture stimulated with epidermal growth factor (EGF) to determine if
      p36 expression was related to DNA synthesis or to the effect of the extracellular
      matrix on hepatocyte differentiation; ethanol was employed as an agent to inhibit
      hormone stimulated hepatocyte DNA synthesis. It was found that hepatocyte p36
      expression was highly dependent on the type of extracellular matrix and the time
      in culture. There was no correlation of p36 expression with DNA synthesis and,
      therefore, p36 levels appeared more closely related to the differentiated
      phenotype, induced by the extracellular matrix interactions rather than cellular
      proliferation.

PMID- 7504478
TI  - Cloning and expression of a rat neuronal nitric oxide synthase coding sequence in
      a baculovirus/insect cell system.
AB  - A DNA sequence encoding rat neuronal NO synthase (nNOS) was isolated and cloned
      into the baculovirus expression vector pVL1393 to generate pVLRBNOS. Transfection
      of Spodoptera frugiperda Sf-21 cells with the construct pVLRBNOS resulted in the
      synthesis of high levels of neuronal NO synthase. Analysis of the expression
      pattern revealed soluble, enzymatically active NO synthase in the cytoplasm of
      cell extracts. Active enzyme could also be purified from culture supernatants
      using 2'-5' ADP sepharose affinity chromatography. This enzyme was recognised by
      antibodies to the native nNOS and showed a similar degree of inhibition by
      arginine analogs as the native nNOS. The majority of the NOS synthesised had
      accumulated as insoluble "inclusion-body" material. The purification of
      recombinant nNOS from insect cells should facilitate characterisation of neuronal
      NO synthase.

PMID- 7504479
TI  - A general method for screening mAbs specific for G-protein coupled receptors as
      exemplified by using epitope tagged BLR1-transfected 293 cells and solid-phase
      cell ELISA.
AB  - Monoclonal antibodies (mAb) against G-protein coupled receptors are rare. In this
      study we describe a cell ELISA-based screening system for monoclonal antibodies
      specific for the G-protein coupled receptor BLR1 (Eur. J. Immunol. 1992. 22:2795)
      using human embryonic kidney 293 cells transfected with a modified human BLR1
      cDNA directing the synthesis of an epitope tagged BLR1 protein. Lou/C rats were
      immunized with BLR1 transfected, tagged 293 cells and after fusion of spleen
      cells with X63 Ag8.653 myeloma cells supernatants were tested for BLR1 specific
      antibodies by comparing the binding to BLR1 transfected 293 cells and to
      untransfected control cells immobilised on poly-L-lysine coated microtiter
      plates. Cells were fixed with 2% paraformaldehyde and permeabilized using
      digitonin in order to allow binding of mAb directed against intracellular
      epitopes. This mild fixation retained excellent morphology of 293 cells and
      allowed reliable binding to the trays. Screening of approximately 2500
      supernatants identified 19 antibodies binding to BLR1 transfected 293 cells but
      not to control 293 cells. One of these mAb specifically bound to the G-protein
      coupled receptor BLR1.

PMID- 7504480
TI  - Phosphorylation of the carboxyl-terminal domain of the zeta 1 subunit is not
      responsible for potentiation by TPA of the NMDA receptor channel.
AB  - The carboxyl-terminal domain of the zeta 1 subunit of the mouse NMDA receptor
      channel produced as a fusion protein with GST was phosphorylated in vitro by PKC.
      A mutant of the zeta 1 subunit without serine or threonine residues in the
      carboxyl-terminal domain (zeta 1-2-NST) was constructed and was expressed alone
      or together with the epsilon 2 subunit in Xenopus oocytes. Current responses of
      the zeta 1-2-NST homomeric and epsilon 2/zeta 1-2-NST heteromeric NMDA receptor
      channels were enhanced by treatment with TPA, a PKC activator, and the extents of
      potentiation were comparable with the corresponding wild-type channels. These
      results suggest that the phosphorylation of the carboxyl-terminal domain of the
      zeta 1 subunit is not responsible for potentiation of NMDA receptor channels by
      the TPA treatment.

PMID- 7504481
TI  - N omega-hydroxy-L-arginine, a reactional intermediate in nitric oxide
      biosynthesis, induces cytostasis in human and murine tumor cells.
AB  - Conversion of L-arginine to L-citrulline and nitric oxide (NO) by NO synthase
      induced in the murine EMT-6 cells resulted in the release of a large amount of
      the stable reactional intermediate N omega-hydroxy-L-arginine into the
      extracellular medium. We have prepared [3H]N omega-hydroxy-L-arginine
      biosynthetically, and shown that, after its uptake, this molecule can induce
      cytostasis in NO synthase-deficient P-815 and U-937 tumor cells. This long-lived
      intermediate could behave as a supplier of NO or other toxic molecules in cell
      cell interactions.

PMID- 7504483
TI  - Topological characterization of the lymphoid-specific seven transmembrane
      receptor BLR1 by epitope-tagging and high level expression.
AB  - We have tagged the human lymphocyte-specific G-protein-coupled receptor BLR1
      either with an amino-terminal or a carboxyl-terminal epitope-tag recognized by an
      anti-MYC monoclonal antibody. Flow cytometry was used to determine the efficiency
      of transient transfections and to establish human embryonic kidney 293 cell
      clones showing stable high level expression of BLR1. Analysis of permeabilized
      versus non-permeabilized transfected 293 cells demonstrated that BLR1 is an
      integral plasma membrane protein, topologically oriented therein as predicted for
      other members of this class of seven pass membrane receptors. In addition, BLR1
      was expressed in 293 cells to high levels as a glycosylated membrane protein. The
      easily detectable and assayable expression of tagged G-protein-coupled receptors,
      as exemplified for BLR1 in 293 cells, provides a suitable system for further
      functional studies and offers an efficient screening tool for the identification
      of receptor-specific antibodies, ligands, or receptor-associated proteins.

PMID- 7504482
TI  - Nitric oxide production from macrophages is regulated by arachidonic acid
      metabolites.
AB  - In activated macrophages the inducible form of the enzyme nitric oxide (NO)
      synthase generates high amounts of the toxic mediator NO. After 20 h of treatment
      with LPS rat peritoneal macrophages release 12-16 nmol NO2-/10(5) cells which is
      detectable in the culture supernatant by the Griess reaction as a measure of NO
      formation. The addition of aminoguanidine (1 mM), a preferential inhibitor of the
      inducible NO-synthase, completely abolished NO2-accumulation. Incubation with
      indomethacin or acetyl-salicylic acid, preferential inhibitors of the
      cyclooxygenase pathway of the arachidonic acid metabolism, did not influence NO2-
      levels. Nordihydro-guaiaretic acid (50 microM), a preferential inhibitor of the
      lipoxygenase pathway, caused strong reduction of NO2- accumulation to 1.9 +/- 0.3
      nmol/200 microliter. Simultaneous inhibition of cyclo- and lipoxygenase by BW755c
      resulted in an intermediate effect (7.3 +/- 1.1 nmol/200 microliter NO2-). These
      results show that the induction of NO production in activated macrophages is
      regulated by products of the lipoxygenase-pathway of the arachidonic acid
      metabolism.

PMID- 7504484
TI  - Nitric oxide and nitric oxide synthase mRNA induction in mouse islet cells by
      interferon-gamma plus tumor necrosis factor-alpha.
AB  - It has been shown that nitric oxide (NO) is involved in islet cell damage induced
      by interleukin-1 (IL-1). Here we show that interferon-gamma (IFN-gamma) and tumor
      necrosis factor-alpha (TNF-alpha) synergistically induced NO production and
      inducible NO synthase (iNOS) mRNA expression in mouse islet cells. Cycloheximide
      (CXH) did not prevent the iNOS mRNA expressions. The combination of IFN-gamma and
      TNF-alpha, which is highly cytotoxic to mouse islet cells, failed to destruct
      islet cells in the absence of L-arginine or in the presence of NG-monomethyl-L
      arginine (NMMA). These observations suggest that NO is a primary effector in
      islet cell damage caused by IFN-gamma plus TNF-alpha.

PMID- 7504485
TI  - NG-nitro-L-arginine methyl ester does not affect balloon catheter-induced intimal
      hyperplasia in rats.
AB  - The L-arginine derived NO-cGMP pathway's role in the response of the arterial
      wall to balloon catheter injury was examined. Rats were given the nitric oxide
      synthase inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg po twice daily) or
      vehicle for 6 days before and 2 weeks after balloon catheter injury. NG-nitro-L
      arginine methyl ester treatment increased blood pressure and inhibited
      acetylcholine responses in aortic rings but did not alter the lesions produced by
      balloon injury. Our results suggest that the L-arginine derived NO-cGMP pathway
      does not play a significant role in the response of the artery wall to balloon
      injury in the rat.

PMID- 7504486
TI  - Cytotoxic effect of free bleomycin A5-iron (II) complex and its conjugates with
      concanavalin A, insulin and calcitonin on mouse thymocytes.
AB  - The possibility of using the antibiotic bleomycin as a part of a hybrid molecule
      consisting of a targeting fragment and a generator of reactive oxygen species has
      been investigated. The bleomycin-iron (II) complex was shown to destroy the
      plasma membrane of thymocytes by producing reactive oxygen species. Antioxidants
      protected the cells from destruction thus pointing to its free-radical mechanism.
      The protective effects of catalase and superoxide dismutase indicate that
      superoxide radical and hydrogen peroxide being formed during autooxidation of the
      complex are involved in cell damage. The covalent binding of bleomycin to
      targeting molecules (concanavalin A, insulin, and calcitonin) enhanced the
      ability of the bleomycin-iron (II) complex to destroy the plasma membrane of
      thymocytes.

PMID- 7504487
TI  - Study of interaction of carprofen and its enantiomers with human serum albumin-
      I. Mechanism of binding studied by dialysis and spectroscopic methods.
AB  - The binding of carprofen, a non-steroidal anti-inflammatory drug of the aryl
      propionic acid class [2-(6-chlorocarbazole)propionic acid], and its enantiomers
      to human serum albumin (HSA) has been studied by dialysis and spectroscopic
      methods. Binding parameters obtained by different methods were in close
      agreement. The binding of carprofen to HSA by both fluorescence and equilibrium
      dialysis (ED) methods is characterized by two sets of association constants [K1 =
      5.1 x 10(6) M-1 (fluorescence) and 3.7 x 10(6) M-1 (ED), K2 = 3.7 x 10(5) M-1
      (fluorescence) and 1.3 x 10(5) M-1 (ED)]. The S(+)-enantiomer of carprofen showed
      slightly higher affinity for HSA than its corresponding antipode by both methods.
      Different analyses of the binding to HSA suggested the presence of one high
      affinity site and five to seven low affinity sites for carprofen and its
      enantiomers on HSA. Fluorescence displacement data implied that carprofen
      primarily binds to site II, the benzodiazepine site, while the low affinity site
      of carprofen is site I, the warfarin site. Circular dichroism data suggested
      different mechanisms for the high affinity and the low affinity binding of
      carprofen to HSA. The data are consistent with the major part of the binding
      energy at site II being electrostatic and hydrophobic interactions, whereas for
      the low affinity binding, hydrophobic interactions. Binding was exothermic,
      entropy driven and spontaneous, as indicated by the thermodynamic analyses. From
      binding data with chemically modified HSA derivatives, it is likely that
      tyrosine, lysine and histidine residues are especially involved in carprofen
      binding to HSA, and it is most likely that the high affinity binding of carprofen
      is located in the N-terminal part of domain III or that section of protein plus
      the C-terminal part of domain II of the HSA molecule. When the binding of
      carprofen to HSA was compared to the binding of carprofen methyl ester to HSA (K
      = 0.1 x 10(6) M-1), the carboxyl group of carprofen was found to play an
      important role especially in the high affinity binding of carprofen to HSA. The
      high affinity of carprofen to HSA was independent of the conformational changes
      on HSA caused by N-B transition.

PMID- 7504488
TI  - NAD depletion after in vitro exposure of murine lung slices to bleomycin.
AB  - Bleomycin (BLM), a DNA-cleaving, antitumor antibiotic, causes pulmonary fibrosis.
      It also causes cell injury and activates the nuclear enzyme poly(ADP-ribose)
      polymerase (PAP; EC 2.4.2.30) in lung slices exposed to the drug in vitro. 3
      Aminobenzamide (3-AB), a PAP inhibitor, prevents enzyme activation and cell
      injury. We have examined the potential role of ATP and NAD depletion in injury of
      BLM-sensitive C57B1/6N and -resistant BALB/cN murine lung slices treated with BLM
      or deprived of glucose, the major metabolic substrate of lung. Lung slices either
      were treated for 45 min with injurious concentrations of BLM (10-500
      micrograms/mL) or were incubated without glucose, in the presence or absence of
      2.5 mM 3-AB. Only the highest concentration of BLM, 500 micrograms/mL, caused any
      ATP depletion, and this 35% decrease was transient, occurring at 220 min in
      C57B1/6N slices. In contrast, glucose deprivation caused 50-70% ATP depletion in
      slices from both strains. BLM alone at 100 and 500 micrograms/mL caused a
      sustained 30-70% NAD depletion from 75 min through 400 min in C57B1/6N mouse lung
      slices. In the resistant BALB/cN lung slices, NAD depletion by BLM was only seen
      at 400 min. 3-AB almost completely antagonized NAD depletion in slices from both
      strains. In contrast to BLM, glucose deprivation did not decrease NAD levels
      unless 3-AB was present in C57B1/6N slices. Thus, ATP depletion may play a role
      in the injurious effects of glucose deprivation, but does not appear to be a
      major factor in pneumocyte injury caused by BLM. NAD depletion or other effects
      of PAP activation appear to account for the strain-selective, injurious effect of
      BLM on lung tissue.

PMID- 7504489
TI  - Immunohistochemical analysis of 3-B-(-) and 7-D-4 epitope expression in canine
      osteoarthritis.
AB  - OBJECTIVE: To examine the distribution of the 3-B-3(-) and 7-D-4 epitopes in
      proteoglycans from morphologically normal and osteoarthritic (OA) canine
      articular cartilage. METHODS: Cartilage samples from the femurs of stable and
      destabilized stifle joints of 9 dogs that had undergone transection of the
      cranial cruciate ligament were examined by immunohistochemistry. RESULTS: The 3-B
      3(-) and 7-D-4 epitopes were expressed in the superficial zone of cartilage from
      the destabilized femorotibial joints in the early stages of developing OA. The
      staining patterns with these two antibodies differed, with 3-B-3(-) reactivity
      confined to the superficial and upper middle zones of the articular cartilage,
      and 7-D-4 reactivity more prominent in the matrix, extending into the deeper
      zones and increasing with progression of the lesion. Both epitopes were also
      expressed in the superficial and upper middle zones of areas peripheral to the
      lesions and were detectable before the loss of matrix and proteoglycans could be
      identified by histochemical staining with toluidine blue. CONCLUSION: In this
      study, the expression of atypical chondroitin sulfate proteoglycans was
      demonstrated in osteoarthritic canine cartilage, and the pattern of expression
      changed as the lesions progressed. The occurrence of 3-B-3(-) and 7-D-4 epitopes
      appears to be associated with changes in chondrocyte metabolism in the early
      stages of cartilage degeneration in experimental osteoarthritis.

PMID- 7504490
TI  - Winners of the 1993 ACR slide competition and future plans for the clinical slide
      collection on the rheumatic diseases. The ACR Audiovisual AIDS Subcommittee.

PMID- 7504492
TI  - Substance P-immunoreactive astrocytes in gracile sensory nervous tract of spinal
      cord in gracile axonal dystrophy mutant mouse.
AB  - In the gracile axonal dystrophy (GAD) mutant mouse, the dying-back type axonal
      dystrophy of the primary afferent neurons in the gracile tract of the spinal cord
      was marked by severe gliosis characterized by the hypertrophy and proliferation
      of the fibrous astrocytes. Immunocytochemical observation for substance P (SP)
      revealed that SP-positive cells increased in the lesioned sites, primarily in the
      gracile nucleus of the medulla and subsequently in the gracile fasciculus of the
      spinal cord. The combined immunostaining of both SP and glial fibrillary acidic
      protein (GFAP) indicated that a strong correspondence exists between GFAP
      positive networks and SP-positive grains, suggesting that SP was accumulated in
      the cytoplasm of astrocytes. The networks of SP-positive astrocytes spread all
      over the gracile tract and were densest at the subpial membrane. Similar lesions
      and SP activity were detected along the marginal zone of the lateral and ventral
      funiculi. Using an electron microscope, in addition to SP-positive axonal
      terminals in the gracile nucleus, most SP-positive cells in the gracile tract
      were identified as reactive astrocytes whose processes surrounded myelinated and
      nonmyelinated axons, and extended their foot processes to the blood vessels. By
      in situ hybridization histochemistry of SP mRNA, we confirmed the synthesis of SP
      in the astrocytes. Although the functional significance of SP within astrocytes
      is not established here, these results imply that the astrocytes may play a role
      as a gliotransmitter through which the progress of axonal degeneration in the
      spinal cord was modified.

PMID- 7504491
TI  - Serum amyloid A (SAA): an acute phase protein and apolipoprotein.
AB  - Serum amyloid A (SAA) proteins comprise a family of apolipoproteins coded for by
      at least three genes with allelic variation and a high degree of homology between
      species. The synthesis of certain members of the family is greatly increased in
      inflammation. However, SAA is not often used as an acute-phase marker despite
      being at least as sensitive as C-reactive protein. SAA proteins can be considered
      as apolipoproteins since they associate with plasma lipoproteins mainly within
      the high density range, perhaps through amphipathic alpha-helical structure. It
      is not known why certain subjects expressing SAA develop secondary systemic
      amyloidosis. There is still no specific function attributed to SAA; however, a
      popular hypothesis suggests that SAA may modulate metabolism of high density
      lipoproteins (HDL). This may impede the protective function of HDL against the
      development of atherosclerosis. The potential significance of the association
      between SAA and lipoproteins needs further evaluation.

PMID- 7504493
TI  - Antitumoral effect of bleomycin+dolomite combination treatment, in mice bearing
      Ehrlich ascites carcinoma.
AB  - Dolomite, a mineral composed of magnesium and calcium carbonates, potentiates the
      antitumoral activity of bleomycin: While 40 days after inoculation, no mice
      survived the Ehrlich ascites tumor burden, 44% of them survived it after
      bleomycin treatment, and 63% after a simultaneous treatment of bleomycin and
      dolomite. The beneficial antitumor effect of dolomite is probably related to its
      high content (12.8%) of magnesium.

PMID- 7504494
TI  - Antiepileptic drugs: future development.
AB  - The development of new compounds for seizure disorders has moved from serendipity
      to screening to newer, more rational approaches. We are entering an exciting era,
      with the advent of novel drugs that may have a profound effect on the manner in
      which we treat patients with epilepsy.

PMID- 7504495
TI  - The targets and genes for antibodies to Z-DNA.
AB  - Antibodies to Z-DNA serve as models for recognition of nucleic acid structure by
      proteins that use peptide loops rather than helix-loop-helix, zinc-finger or
      other recurrent motifs for DNA binding. Anti-Z-DNA antibodies have been elicited
      in rabbits, mice and goats by injection of brominated poly(dG-dC), a stable form
      of Z-DNA. Detailed studies of two mouse monoclonal antibodies to Z-DNA, Z22 and
      Z44, have been reported. Epitopes on Z-DNA have been mapped by both serological
      reactions and n.m.r. spectroscopy. Antibodies Z22 and Z44 recognize different
      sites on the Z-DNA. They are both encoded by members of the VH10 gene family,
      which also encodes known autoantibodies to DNA. Vectors for bacterial expression
      of single-chain Fv molecules have been used to determine the importance of
      specific H- and L-chain combinations and particular CDR3 sequences for Z-DNA
      binding. Changes in the H-chain CDR3 cause a decrease in the highly selective Z
      DNA binding and an increase in autoantibody-like binding of B-DNA and single
      stranded DNA.

PMID- 7504496
TI  - PCR-based construction of subtractive cDNA library using magnetic beads.

PMID- 7504497
TI  - Construction of subtractive cDNA libraries from limited amounts of mRNA and
      multiple cycles of subtraction.
AB  - A new strategy to construct subtractive cDNA libraries was developed. The method
      was based on multiple subtraction cycles from small amounts of RNA using
      paramagnetic technology. An additional application of this technique is the
      potential to recover (and reuse) the same mRNAs or the single-stranded cDNA from
      the solid paramagnetic support. The result was assessed in the generation of a
      specific prepuberal mouse testis library.

PMID- 7504498
TI  - Inhibition of DNA hybridization following partial dUTP substitution.
AB  - Carry-over contamination from PCR products can yield persistent false-positive
      results leading to significant problems in the resolution of true positive
      results. Commercial kits used in many laboratories help prevent carry-over
      contamination. We present data on the effects of dUTP substitution on the
      hybridization properties of amplified DNA using alkaline phosphatase conjugated
      oligonucleotide probes. We observe a pronounced depression in hybridization
      signal intensity in some dUTP-substituted PCR products. The magnitude of the
      decreased hybridization signal intensity appears proportional to both the dUTP
      concentration in the amplification reaction and the fraction of thymidylate
      residues in the probe binding site. The hybridization signal is nearly eliminated
      from PCR products synthesized in the presence of dUTP only and where the probe
      binding site is particularly rich in thymidylate residues. The decrease in
      hybridization signal is not always restored with less stringent hybridization
      conditions. Conditions that permit efficient hybridization and detection of bound
      probe but do not compromise carry-over protection are discussed.

PMID- 7504499
TI  - Impact of previously unrecognized benign prostatic hyperplasia on the daily
      activities of middle-aged and elderly men.
AB  - To assess the importance of benign prostatic hyperplasia on activities of daily
      living, a cross-sectional survey of 1627 men aged 40-79 years (representing a 65%
      response rate) registered with two health centres in central Scotland was carried
      out, using a urinary symptom questionnaire and uroflowmetry to identify men more
      likely to have benign prostatic hyperplasia. The condition was defined as a
      prostate gland of more than 20 g in the presence of symptoms of urinary
      dysfunction and/or a peak flow rate of less than 15 ml s-1, without evidence of
      malignancy. Transrectal ultrasonography was used to measure the volume (and by
      inference weight) of prostate glands. A total of 410 men satisfied the criteria
      for benign prostatic hyperplasia. Overall, 51% of men with benign prostatic
      hyperplasia reported interference with at least one of a number of selected
      activities of daily living as a result of urinary dysfunction, compared with 28%
      of men who did not have this condition. In 17% of men of working age (40-64
      years) with benign prostatic hyperplasia, this interference occurred most or all
      of the time for at least one activity of daily living compared with only 3% of
      men in the same age group who did not have this condition. If the criteria of
      unmet need for treatment of benign prostatic hyperplasia constitutes interference
      by urinary dysfunction most or all of the time in at least one activity of daily
      living, then the findings of this survey suggest that a substantial number of
      middle aged and elderly men living in the United Kingdom may be in need of
      assessment and treatment for this condition.

PMID- 7504500
TI  - Study of Listeria monocytogenes contamination in a dairy plant and
      characterization of the strains isolated.
AB  - From 1988 to 1990, a dairy plant was examined for Listeria contamination. Three
      hundred and forty samples were collected and analysed for the presence of
      Listeria. Sixty-one Listeria strains (L. monocytogenes, 44, and L. innocua, 17)
      were isolated from four varieties of cheese, cheese brines, process equipment and
      plant environment. The L. monocytogenes strains were recovered during the
      ripening and rind washing stages and not before, so it is likely that cheese
      contamination occurred at these points in the manufacturing process. The
      characterization of the isolated L. monocytogenes strains by serotyping and phage
      typing showed different serovars and phagovars. Some strains with the same
      serovar and the same phagovar were isolated from cheeses and process equipment
      (shelves) indicating that cheese contamination occurs during ripening. Only one
      profile was found from the analysis of the ribosomal ribonucleic acid (rRNA) gene
      restriction patterns of 38 L. monocytogenes strains with different serovars and
      phagovars. This suggests that all L. monocytogenes strains isolated in the dairy
      plant could have been derived from a single ancestral group.

PMID- 7504501
TI  - Current status of G-CSF in support of chemotherapy and radiotherapy.
AB  - It is now 2 years since the commercial availability of G-CSF, and thus it seems
      appropriate to reassess the clinical merits of this cytokine in the context of
      current knowledge; such an evaluation seems best founded not only on an analysis
      of the biology of G-CSF itself, but also on a critical assessment of whether its
      biologic actions translate into a cost-effective alleviation of patient suffering
      and improved cancer cure. As is so often the case, the knowledge base upon which
      clinicians must rely to make prescribing decisions is smaller than we might wish,
      but a substantial body of existent information can provide a guide to clinical
      strategy until a number of ongoing trials give more concrete information.

PMID- 7504502
TI  - The renal nerves in the newborn rat.
AB  - Immunocytochemical methods were used to investigate the distribution of afferent
      [calcitonin gene-related peptide-(CGRP) immunoreactive and substance P
      immunoreactive] nerves and efferent (neuropeptide Y-immunoreactive and dopamine
      beta-hydroxylase-immunoreactive) nerves in the kidneys of rats within the 1st day
      of life. The newborn rat kidney possesses an afferent and efferent innervation.
      Both afferent and efferent nerves reach the kidney in the same bundles. The
      afferent sensory fibers predominate overwhelmingly in the renal pelvis and ureter
      while the efferent fibers clearly predominate in the vasculature. The
      corticomedullary connective tissue contains both types of innervation with a more
      prominent afferent innervation (CGRP immunoreactive). Only afferent arterioles of
      perihilar nephrons were innervated by efferent sympathetic fibers. The
      distribution and extent of afferent and efferent innervation is consistent with
      the renal nerves playing a significant role in the transition from fetal to
      newborn life. The close proximity between afferent and efferent fibers suggests a
      possible interaction between the two systems.

PMID- 7504506
TI  - Sweet's syndrome associated with G-CSF.
AB  - Sweet's syndrome (SS) developed in two patients with acute myeloid leukaemia
      (AML) treated with granulocyte colony stimulating factor (G-CSF) for febrile
      neutropenia due to AML chemotherapy. Fever, painful skin and conjunctival lesions
      developed and neutrophilic infiltration was detected at biopsy specimens.
      Neutrophilia was not detected. Skin lesions regressed within 1-2 weeks and
      conjunctival lesions within 4 weeks following the cessation of G-CSF. We conclude
      that SS may be a complication of G-CSF therapy and tender skin and/or
      conjunctival lesions developing during G-CSF therapy should suggest the
      possibility of SS.

PMID- 7504505
TI  - Absorption of the stable prostacyclin analogue iloprost through the ulcer base in
      chronic venous insufficiency.
AB  - Iloprost, a stable prostacyclin analogue, is known to have beneficial effects on
      the disturbed microcirculation. To develop a topical application for venous leg
      ulcers it is necessary to know the extent to which iloprost might be absorbed
      through the ulcer base. The aim of this study was to measure the absorption
      kinetics of iloprost solutions in increasing concentrations and doses (0.004% [15
      micrograms]-0.006% [30 micrograms]) in 23 patients. There was considerable
      variation amongst the patients in the amount of iloprost absorbed. In 40% of
      patients no iloprost could be detected in the plasma, whereas in others up to 82%
      of the iloprost applied was absorbed through the ulcer base. High iloprost plasma
      levels provoked flushing in two patients. The highest plasma levels were always
      reached during the first hour after application. There was no direct relation
      between the ulcer size and the amount of iloprost absorbed. Iloprost
      concentrations up to the highest concentration applied (0.006%) were well
      tolerated locally.

PMID- 7504504
TI  - The role of cytokines in the generation of skin lesions in dermatitis
      herpetiformis.
AB  - The infiltration of polymorphonuclear neutrophils (PMN) into the upper dermis
      which characterizes the skin lesions of dermatitis herpetiformis (DH) has never
      been satisfactorily explained. This study has shown that lesional skin of
      patients with DH has increased expression of endothelial leucocyte adhesion
      molecules (ELAM) in the deep dermis, combined with a markedly increased staining
      for interleukin 8 (IL-8) in the basal epidermal layer. Dendritic cells which
      stained for granulocyte macrophage colony stimulating factor (GM-CSF) were also
      observed at the dermo-epidermal junction, and this phenomenon was more pronounced
      in lesional than in uninvolved DH skin. ELAM, IL-8 and GM-CSF are known to
      promote infiltration and activation of PMN, and it is suggested that these
      cytokines may play a key role in the generation of DH lesions.

PMID- 7504507
TI  - Haemopoietic CD34+ progenitor cells are not infected by HIV-1 in vivo but show
      impaired clonogenesis.
AB  - We evaluated the role of CD34+ bone marrow progenitor cells in vivo, in the
      pathogenesis of AIDS-related haematological abnormalities. The clonogenic
      activity of CD34+ cells from seven patients with HIV-1 infection, without bone
      marrow involving opportunistic infections or neoplasms, was assessed in semisolid
      cultures. The number of CFU-GM was significantly reduced as compared to the
      controls (P = 0.017), independently from myelotoxic therapy, while the number of
      BFU-E was not. The presence of retroviral sequences in CFU-GM colonies from four
      patients and in the total population of CD34+ cells from six patients with
      advanced stage HIV infection was investigated using the polymerase chain
      reaction. The presence of HIV-1 sequences was also searched for in a purified
      suspension of CD34+ cells after 3 weeks liquid culture. All these cells were
      always HIV-1 negative, while viral sequences were always detected in bone marrow
      mononuclear cells from these and other patients. The number of HIV-1 DNA copies
      decreased with increasing enrichment. At most 1:10,000 CD34+ cells are infected
      in vivo. Other mechanisms than direct viral infection of progenitor cells must
      account for the defective haemopoiesis in HIV-1 infected patients.

PMID- 7504503
TI  - The molecular structure of the antidiuretic hormone elicited water channel.
AB  - Measurements of osmotic water permeability (Pf) have shown that the plasma
      membranes of human red cells and certain epithelial cells possess specialized
      water channels. Although these water channels have been characterized extensively
      using biophysical techniques, the proteins that compose these unique channels
      have only recently been identified. Antidiuretic hormone (ADH) stimulation
      rapidly increases collecting duct epithelial cell Pf by fusion of water channel
      containing vesicles (WCV) with their apical membranes. The proteins of WCV from
      toad bladder and rodent kidney have been characterized. The principal proteins in
      toad bladder WCV are 55,000 daltons (55 kDa) and 53 kDa and span the lipid
      bilayer of these vesicles. Polyclonal antisera raised against the 55-kDa and 53
      kDa proteins inhibit ADH-stimulated toad bladder Pf by 80% and recognize protein
      bands of 46, 38 and 30 kDa in mouse kidney. Purification of WCV from rat kidney
      reveals enrichment of the 46-kDa protein. Recently, a 28-kDa integral membrane
      protein (called CHIP-28) has been isolated from human red cells. It forms
      functional water channels in Xenopus oocytes and when reconstituted into
      proteoliposomes. Large amounts of CHIP-28 protein are present in epithelial cells
      of the proximal tubule and descending thin limb of Henle's loop. Molecular
      cloning efforts are underway to elucidate the structure and function of these
      candidate water channel proteins.

PMID- 7504508
TI  - Impaired G-CSF production at post-transcriptional level in a patient with chronic
      idiopathic neutropenia.
AB  - Chronic idiopathic neutropenia (CIN) is a disorder characterized by severe
      neutropenia and a maturational arrest of the neutrophil precursors in the bone
      marrow. The pathogenesis of this disorder has been obscure. We examined the
      production of endogenous G-CSF and the expression of G-CSFmRNA in a patient with
      adult type CIN. The G-CSF production by the patient's mononuclear cells was
      deficient in spite of the adequate accumulation of G-CSFmRNA. Our data suggests
      that the defect in the endogenous G-CSF production at the post-transcriptional
      level is likely to be an aetiological factor in CIN.

PMID- 7504509
TI  - Peripheral blood stem cell mobilization using high-dose cyclophosphamide and G
      CSF in pretreated patients with lymphoma.
AB  - Peripheral blood stem cell (PBSC) mobilization for autologous transplantation is
      more difficult in treated patients and those with bone marrow involvement. In 17
      pretreated lymphoma patients, cyclophosphamide (4 g/m2) and G-CSF mobilized a
      median circulating peak of 1959 CFU-GM/ml on day 12.5. PBSC harvesting commenced
      when WBC was 1 x 10(9)/l at day 10.5 collected a median of 21.2 x 10(4)/CFU
      GM/kg. 13/17 (76%) patients exceeded the 10 x 10(4) CFU-GM/kg threshold for
      engraftment. The CFU-GM yield was significantly higher in patients whose WBC
      recovered from 1-5 x 10(9)/l in less than 3 days and correlated with the maximum
      WBC pre and post the cyclophosphamide induced nadir. This regime safely mobilized
      adequate PBSC in the majority of pretreated lymphoma patients.

PMID- 7504511
TI  - Serum stem cell factor concentration in patients with myelodysplastic syndromes.
AB  - Stem cell factor (SCF) is characterized by its capacity to synergize dramatically
      with other haemopoietic growth factors in in vitro erythroid, myeloid, and
      lymphoid progenitor culture systems. We have measured serum SCF concentrations by
      enzyme immunoassay in 85 patients with myelodysplasia (MDS). Serum samples were
      taken in 1988-89 and in 1991-92 and stored at -20 degrees C. Mean serum SCF
      concentration in the MDS patients was 2.81 ng/ml (range 0.6-8.0). This was
      significantly lower (P = 0.0001) than the values for 234 normal subjects; mean
      3.30 ng/ml (range 1.3-8.0). No significant relationship between SCF concentration
      and peripheral blood counts, bone marrow parameters, red cell transfusion status,
      survival or FAB subtype was found, although a trend of decreasing SCF
      concentration from refractory anaemia through sideroblastic anaemia and chronic
      myelomonocytic leukaemia to refractory anaemia with excess blasts was seen. The
      reduced SCF serum concentration in some patients with myelodysplasia suggests a
      rationale for therapy with recombinant SCF in these patients.

PMID- 7504510
TI  - Different membrane expression of CD11b and CD14 on blood neutrophils following in
      vivo administration of myeloid growth factors.
AB  - During the administration of recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) or granulocyte-macrophage CSF (rhGM-CSF) we studied the early
      and late changes of membrane antigen density on neutrophils. RhG-CSF and rhGM-CSF
      both caused an early transient reduction in blood neutrophilic granulocyte
      concentration within the first 30 min after treatment followed by a marked later
      increase during the subsequent 24 h. During the early neutropenia quantitative
      flow cytometry showed an associated marked increase in the density of membrane
      CD11b from 169 x 10(3) before to 568 x 10(3) A.U. per cell induced by rhGM-CSF
      but a non-significant change by rhG-CSF, suggesting that different mechanisms may
      be responsible for the transient neutropenia. The subsequent neutrophil
      granulocytosis was followed by a significantly (P < 0.05) increased density of
      the CD14 antigen from 6.1 x 10(3) before to 15.9 x 10(3) A.U. per cell during
      treatment with rhG-CSF, but not by rhGM-CSF administration. These results
      demonstrate that the two cytokines may affect the function of neutrophilic
      granulocytes in different ways. The increased expression of CD11b could explain
      some of the side-effects during treatment with rhGM-CSF. The upregulation of CD14
      induced by rhG-CSF may be clinically relevant, as CD14 is an opsonic receptor for
      lipopolysaccharide binding proteins, acting in the defence against Gram-negative
      bacterial infections.

PMID- 7504512
TI  - Molecular and functional diversity of cloned cardiac potassium channels.
AB  - Action potential duration is an important determinant of refractoriness in
      cardiac tissue and thus of the ability to propagate electrical impulses. Action
      potential duration is controlled in part by activation of K+ currents. Block of
      K+ channels and the resultant prolongation of action potential duration has
      become an increasingly attractive mode of anti-arrhythmic intervention. Detailed
      investigation of individual cardiac K+ channels has been hampered by the presence
      of multiple types of K+ channels in cardiac cells and the difficulty of isolating
      individual currents. We have approached this problem by employing a combination
      molecular cloning technology, heterologous channel expression systems, and
      biophysical analysis of expressed channels. We have focused on six different
      channels cloned from the rat and human cardiovascular systems. Each channel has
      unique functional and pharmacological characteristics, and as a group they
      comprise a series of mammalian K+ channel isoforms that can account for some of
      the diversity of channels in the mammalian heart. Each channel appears to be
      encoded by a different gene with little or no evidence for alternate splicing of
      RNA transcripts to account for the differences in primary amino acid sequence. In
      addition to the unique kinetic properties of these channel isoforms when
      expressed as homotetrameric assemblies, the formation of heterotetrameric K+
      channels is also observed. The formation of heterotetrameric channels from the
      different gene products to create new channels with unique kinetic and
      pharmacological properties might further account for cardiac K+ channel
      diversity.

PMID- 7504513
TI  - Three non-overlapping regions of chromosome arm 11p allele loss identified in
      infantile tumors of adrenal and liver.
AB  - Tumor and constitutional chromosome arm 11p genotypes were compared in 6
      hepatoblastoma (HB) patients and 2 adrenal adenoma (AA) patients, with one HB
      patient and both AA patients displaying clinical features associated with the
      Beckwith-Wiedemann syndrome (BWS). Using up to 14 chromosome 11 polymorphic
      markers, loss of constitutional heterozygosity (LOH) was demonstrated in both AA
      patients and in 4 of 6 HB patients. This identified three distinct and non
      overlapping regions of 11p within which LOH occurred, which were defined as lying
      distal to the gamma-globin locus (11p15.5), proximal to the gamma-globin locus
      but distal to 11p13 (LOH being detected at 11p15.1), and restricted to the 11p13
      region. Specific LOH within each 11p15 region was observed in HB, and this
      represents the first demonstration by a single study of LOH clearly affecting
      separate regions of chromosome band 11p15 in a particular tumor type. One AA
      showed LOH restricted to 11p13 loci, implicating the involvement of the WT1 gene.
      The second AA patient presented with genitourinary abnormalities and we therefore
      examined sequences coding for 3 zinc finger domains of WT1 in both AAs. No point
      mutations were identified in sequence from either patient. Nonetheless our
      results indicate that 3 separate 11p loci may be significant in the development
      of tumors which arise in association with BWS.

PMID- 7504514
TI  - Regional fine mapping of the beta crystallin genes on chromosome 22 excludes
      these genes as physically linked markers for neurofibromatosis type 2.
AB  - Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disease,
      characterized by the development of bilateral vestibular schwannomas. The NF2
      gene has been assigned to chromosome 22. Cataract and other eye abnormalities are
      frequently seen in NF2 patients. The specific association of eye abnormalities
      and NF2 might be caused by a genetic change on chromosome 22 that affects both
      the NF2 gene and a physically linked crystallin gene. In order to test this
      hypothesis, we regionally localized the known crystallin genes (i.e. CRYBB2,
      CRYBB2P1, CRYBB3, and CRYBA4) on chromosome 22. Crystallin gene-specific probes
      were hybridized to an extended panel of human x rodent somatic cell hybrids
      containing various portions of chromosome 22. It was found that all crystallin
      genes map to a very small region on chromosome 22 that is physically separate
      from the NF2 gene region by at least 160 kb of DNA. In addition, we found that
      the beta B crystallin genes (CRYBB2, CRYBB2P1, and CRYBB3) are clustered on a 300
      kb SacII fragment and that the beta A4 crystallin gene (CRYBA4) is not part of
      this cluster. We conclude that the ocular manifestations in many NF2 patients are
      probably not the primary consequence of rearrangements on chromosome 22 that
      involve both the NF2 gene and a nearby beta crystallin gene.

PMID- 7504515
TI  - Localization of two tyrosine kinase receptor genes with respect to the 5q35
      chromosomal breakpoint of Ki-1 lymphoma cell lines.
AB  - The consistency of the breakpoint on chromosome 5 at band 5q35 occurring in Ki-1
      non-Hodgkin's lymphomas is highly suggestive of the involvement of a locally
      altered gene in this disease. In this study, we analyzed the potential
      involvement, in the translocation, of two receptor tyrosine kinase genes and
      putative oncogenes, FLT4 and FGFR4, previously localized near this breakpoint.
      Fluorescence in situ chromosomal hybridization allowed us to refine their
      localization to sub-band 5q35.3 and to show that both genes are translocated to
      the derivative chromosomes in Ki-1 cell lines containing either a t(2;5) or a
      t(3;5). Pulsed-field gel electrophoresis showed that the FLT4 and FGFR4 genes are
      not physically linked, nor are they altered by the translocation. Finally,
      Northern blot analysis showed that neither FLT4 nor FGFR4 is expressed in the Ki
      1 cell lines, suggesting that they are not implicated in the genesis of Ki-1
      lymphomas.

PMID- 7504516
TI  - Direct visualization of the transposed ABL gene in a duplicated masked Ph
      chromosome.
AB  - In a small percentage of cases of chronic myelogenous leukemia (CML), where the
      Ph chromosome is masked because of highly complex translocations and sub
      microscopic rearrangements, precise identification of chromosomal aberrations by
      routine banding techniques has been difficult. We report on a new case of CML in
      which a single copy of a masked Ph chromosome was duplicated during blast crisis,
      i.e., the karyotype was 47,XY,dir ins(22;9)(q11;q34.1q34.2),t(1;22) (q21;q11), +
      der (22)t(1;22)(q21;q11). The chromosome in situ suppression hybridization (CISS)
      technique with whole chromosome 1 and 22 specific painting probes demonstrated
      that 22q11-qter had been translocated to 1q21, whereas 22q11 was the recipient of
      1q21-qter. Furthermore, a cosmid probe identified the location of the ABL gene on
      only one chromosome 9 (band q34). The other ABL gene could be detected on both
      derivative chromosomes 22 at band q11 which was flanked by the translocated part
      of the long arm of chromosome 1, thus providing direct visualization of the ABL
      insertion in a double masked Ph chromosome. A breakpoint within the 5.8 kb major
      breakpoint cluster [M-BCR] region was shown by Southern blotting.

PMID- 7504517
TI  - Rearrangement of 12q14-15 in pulmonary chondroid hamartoma.
AB  - Cytogenetic analysis of a pulmonary chondroid hamartoma showed an inv(12)(p13q14
      15) as the sole abnormality. This finding together with previously reported data
      is an indication that the 12q14-15 region may be nonrandomly involved in the
      pathogenesis of this tumor type.

PMID- 7504518
TI  - Mapping of the 19p13 breakpoint in an ovarian carcinoma between the INSR and TCF3
      loci.
AB  - Chromosome rearrangements involving band 19p13 have been described in about half
      of all ovarian carcinomas. Four ovarian carcinomas with translocations of 19p13
      were investigated with 11 DNA probes for markers localized to this band. All
      markers exhibited normal restriction patterns, suggesting that they were not
      rearranged. The 19p13 breakpoint of one tumor was mapped to a location between
      the INSR and the TCF3 loci.

PMID- 7504519
TI  - Ring chromosome 12 resulting from nonrandom telomeric associations with the short
      arm of chromosome 15 in a cerebellar astrocytoma.
AB  - Ring chromosome 12 was found in an untreated cerebellar astrocytoma apparently
      resulting from nonrandom telomeric associations involving the short arm of
      chromosome 15, and both the long and short arms of chromosome 12. The clonal
      nonrandom telomeric associations of 15p to both ends of the chromosome 12 were
      transitory, but appear to be the precursor lesion in the evolution to ring
      chromosome 12 in this tumor. A multistep process in the formation of a ring
      chromosome resulting from nonrandom telomeric associations to both telomeres is
      illustrated.

PMID- 7504520
TI  - Low frequency of mutations in the WT1 coding region in Wilms' tumor.
AB  - A series of twenty unselected Wilms' tumors were analysed for alterations in the
      WT1 tumor suppressor gene. The entire coding region of WT1 was amplified by RNA
      PCR, and then screened for mutations by single-strand conformational polymorphism
      analysis (SSCP). This method was shown to be capable of detecting point mutations
      in the WT1 gene, by using an experimentally produced mutation. A single mutation,
      a 226 bp intragenic deletion, was detected in a tumor from a patient with the
      WAGR syndrome. These results suggest that alterations in the WT1 gene may be
      involved in only a subset of Wilms' tumors, and that other loci need to be
      investigated as potential suppressor genes in sporadic Wilms' tumors.

PMID- 7504521
TI  - Expanded range of 11q13 breakpoints with differing patterns of cyclin D1
      expression in B-cell malignancies.
AB  - We have analyzed the BCL1 locus in a series of 24 B-cell tumors and cell lines
      with rearrangements of 11q13 (mostly t(11;14)(q13;q32) translocations). Using
      Southern hybridization and/or fluorescence in situ hybridization (FISH) on
      metaphase chromosomes, we have not only confirmed the scattering of the
      breakpoints between the BCL1 locus and the cyclin D1 gene (CCND1), but also shown
      that some of the breakpoints could be as far as 500 kb on either side of the
      latter. Expression of CCND1 was not restricted to cases with t(11;14)(q13;q32),
      but was also associated with other 11q13 rearrangements, such as a
      t(8;11)(p22;q13). Whatever the alteration at 11q13, a correlation was observed
      between the expression of CCND1 and the presence of a breakpoint within 150 kb
      upstream of the gene. On the contrary, three samples, including a bona fide
      t(11;14) translocation and two cases with breakpoints located outside the BCL1
      CCND1 area, did not exhibit detectable levels of CCND1 transcripts. Our results
      raise the possibility that several discrete molecular events can take place at
      11q13 in B-cell malignancies.

PMID- 7504522
TI  - Extensive genetic alterations in prostate cancer revealed by dual PCR and FISH
      analysis.
AB  - The genetic alterations that underlie prostate tumorigenesis are assumed to
      comprise gain or loss of specific chromosomal regions, whole chromosomes, or
      sequence-specific mutations. Existing data have not demonstrated clear
      specificity of whole chromosome or regional chromosomal gain or loss that
      characterizes entire individual malignant lesions, or all malignant lesions,
      within a cancerous prostate. We have analyzed tissues from 13 patients for target
      sequences by using PCR and FISH techniques on paired malignant or prostatic
      intraepithelial neoplastic (PIN) and benign samples (usually from different areas
      of the same paraffin section). We exercised stringent histologic control over
      these samples by examining small (< 5 mm2), discrete regions of sectioned benign,
      malignant, and PIN tissue. The same histologic region was examined on serial
      sections by FISH and PCR analysis. The tissues were examined for numerical
      aberrations involving chromosomes 4 (as a control), 7, 8, 10, and the Y by FISH
      analysis, and for gain or loss of chromosome 7 and chromosomal arms 8p, 10q, and
      Yp by PCR analysis. The concurrent application of PCR and FISH to microdissected
      prostatic tissues yielded evidence of higher frequencies of genetic aberration in
      prostate cancers than those found with either method alone or by other
      approaches. These results indicate the power of simultaneous genetic assays that
      are closely linked to specific tumor histology.

PMID- 7504523
TI  - In situ hybridization to interphase nuclei in acute leukemia.
AB  - Numerical chromosome abnormalities were studied in 17 acute lymphoblastic
      leukemias and one hyperdiploid acute myeloblastic leukemia by fluorescence in
      situ hybridization (FISH) using YAC clones specific to chromosomes 21 and 6. The
      results agreed well with cytogenetic findings. Hyperdiploid leukemias with more
      than 50 chromosomes usually had 4 copies of chromosome 21 and three of chromosome
      6, while diploid and pseudodiploid cases were confirmed to have two copies of the
      two chromosomes. Interesting discrepancies were also observed. In one patient,
      trisomy 6 was detected by FISH but not by cytogenetics because of the probable
      inclusion of a chromosome 6 segment within a marker chromosome. The percentages
      of nuclei with 3 or 4 spots (chromosome 21) and three spots (chromosome 6) in
      hyperdiploid cells were significantly different in some patients, whereas they
      might be identical from cytogenetic data.

PMID- 7504524
TI  - Changes in amniotic arachidonic acid metabolism associated with increased cyclo
      oxygenase gene expression.
AB  - OBJECTIVES: To study the differences in the metabolism of arachidonic acid, to
      prostaglandins and other eicosanoids, between amnion cells before and after
      labour. To study the changes in the expression of the type 1 cyclo-oxygenase gene
      associated with the changes in arachidonic acid metabolism. DESIGN: Amnion cells
      collected before labour, at elective caesarean section, and following spontaneous
      labour and delivery were established in mono-layer culture. Intracellular
      arachidonic acid pools were radio-labelled and the metabolic fate of endogenous
      archidonic acid was then studied using high performance liquid chromatography.
      RNA was extracted from the cell cultures and expression of the cyclooxygenase
      gene was studied using northern hybridisation to a sheep cyclo-oxygenase cDNA.
      RESULTS: Metabolism of endogenous arachidonic acid in amnion cells established in
      culture prior to labour is principally via lipoxygenase and epoxygenase enzyme
      pathways to di- and mono-HETEs and EET with little cyclo-oxygenase metabolism to
      prostaglandins. Following labour there is a large increase in arachidonic acid
      metabolism with a change in the cyclo-oxygenase: lipoxygenase enzyme pathway
      ratio in favour synthesis of prostaglandin E2. Whilst synthesis of lipoxygenase
      metabolites doubles, the increase in prostaglandin E2 synthesis is ten fold.
      Expression of the cyclo-oxygenase gene is significantly greater in cell cultures
      established following spontaneous labour and delivery than in those established
      following elective caesarean section prior to labour. CONCLUSIONS: In association
      with labour there is an increase in arachidonic acid metabolism in amnion cells
      and a change in the ratio of metabolism via cyclo-oxygenase and lipoxygenase
      enzyme pathways to increase synthesis of prostaglandin E2. This change is
      associated with increased expression of the cyclooxygenase gene.

PMID- 7504525
TI  - An active FK506-binding domain of 17,000 daltons is isolated following limited
      proteolysis of chicken thymus hsp56.
AB  - We have previously identified hsp56, a protein component of steroid receptor
      complexes, as an FK506 binding protein [Yem et al. (1992) J. Biol. Chem. 267,
      2868-2871]. We now report that hsp56 is also found to be a major immunophilin in
      chicken thymus, by virtue of binding to FK506-Affi-Gel-10 as well as positive
      cross-reactivity with a polyclonal antiserum directed against human hsp56.
      Limited digests of purified chicken hsp56 with endoproteinase Lys C result in the
      production of a unique polypeptide having a mass of about 17 kDa (p17), as judged
      by Western blotting. Peptide mapping provided additional proof that p17 is a
      fragment which comprises the entire FK506 binding domain I of chicken hsp56,
      terminating with an Arg-Lys which might represent a processing site. Binding of
      radiolabeled dihydro FK506 to p17 is saturable with a calculated KD of 42 nM.
      Since size exclusion chromatography of drug-p17 complexes indicates that the
      active species is a homodimer with a mass of 30-40 kDa, the stoichiometry
      calculated for the drug-protein complex is approximately 1:1. Furthermore, unlike
      FKBP-12, chicken p17 bound to FK506 does not bind to calcineurin-calmodulin
      complexes. This work demonstrates the excision of a domain from an hsp56 protein
      that is active in binding FK506 and functionally distinct from FKBP-12, a protein
      of similar size and structure.

PMID- 7504526
TI  - RNA priming coupled with DNA synthesis on natural template by calf thymus DNA
      polymerase alpha-primase.
AB  - A bovine genomic DNA library was surveyed with respect to the template activity
      for RNA-primed DNA synthesis by calf thymus DNA polymerase alpha-primase complex.
      About 7% of the single-stranded DNA clones contained distinct initiation sites
      consisting of pyrimidine clusters of pyrimidine-rich sequences. The initiation
      sites were located at or near the 3'-end of the pyrimidine clusters. One of these
      sequences, containing a 10-mer pyrimidine cluster with major initiation sites,
      was analyzed in detail. By the successive substitutions of pyrimidines in the
      cluster with oligodeoxydenylate [(dA)n] in the 5' to 3' direction, the minimum
      length of the initiation sequence was estimated to be as long as the 7-mer. In
      contrast, when one or three pyrimidines at the 3'-end of the cluster were
      replaced with (dA)n, the priming activity was largely lost, indicating that these
      pyrimidine residues were indispensable for priming. Furthermore, base
      substitutions of upstream or downstream sequences outside the pyrimidine cluster
      also decreased the total priming frequencies. Interestingly, the base
      substitutions inside or outside of the pyrimidine cluster sometimes caused a
      shift in the major priming sites. These results indicate that the minimum priming
      unit of the CTPPS1 template for RNA-primed DNA synthesis consists of a pyrimidine
      cluster (6-mer) with one purine at its 3'-border and that both the 3'-downstream
      6-bases and the 5'-upstream 17-bases modulate the priming by enhancing the
      priming frequency and/or slightly shifting the sites of initiation of primer
      synthesis. It was also revealed that the lengths of the product RNA primers
      became shorter as the length of pyrimidine cluster was shortened by substitution
      with (dA)n. The gel retardation assay further showed that the complex formation
      between DNA polymerase alpha-primase and the DNA templates was strongly in
      competition with poly(dC), poly(dG), and poly(dT) but not with poly(dA).
      Furthermore, template activities as well as the pyrimidine contents of a series
      of base-substituted DNA correlated well with their affinities to the enzyme, as
      measured by both gel retardation assay and their Km values for the priming
      reaction. Apparently, DNA polymerase alpha-primase primarily recognizes the
      minimum priming unit consisting of a pyrimidine cluster with a purine at the 3'
      boundary of purine, but the initiation of primer RNA synthesis can be modified by
      pyrimidine residues outside of the minimum priming unit.

PMID- 7504527
TI  - Hypothesized neurochemical models for psychiatric syndromes in alcohol and drug
      dependence.
AB  - Exploration of the neurochemistry of psychiatric and substance use disorders in
      dual diagnosis patients may help explain the greater than chance comorbidity of
      these disorders and lead to advances in treatment. This paper will focus on the
      hypothesized neurochemical changes associated with primary substance use
      disorders which might lead to secondary psychiatric disorders by mimicking the
      hypothesized neurochemical changes of primary psychiatric disorders. For example,
      hypothesized serotonergic deficits in alcoholism, endorphin deficits in opioid
      dependence, and dopamine depletion in cocaine dependence all might predispose to
      depression. A vicious cycle of cocaine dependence and depression and a vicious
      cycle of alcohol and drug dependence and panic anxiety are reviewed as models for
      hypothesized alcohol or drug withdrawal related neurochemical changes
      predisposing to continued chemical dependency. Exploration of the neurochemistry
      of dual diagnosis patients reinforces the need for treatment approaches that take
      into account both aspects of illness.

PMID- 7504528
TI  - Macrophages and acute-phase proteins.

PMID- 7504529
TI  - The role of macrophages and macrophage cytokines in host resistance to herpes
      simplex virus.

PMID- 7504530
TI  - Interactions of lipopolysaccharide with macrophages.

PMID- 7504531
TI  - Receptors on phagocytic cells involved in microbial recognition.
AB  - There are two general concepts that we hope to have stressed concerning the
      recognition of microbes by phagocytic cells. The first is the concept of receptor
      redundancy and receptor cooperatively. Multiple receptors on leukocytes often
      participate in a given microbial recognition event. This concept can be
      illustrated by leishmania promastigotes that utilize both mannose receptors and
      Mac-1 to bind efficiently to macrophages. Likewise, macrophages use receptors for
      both IgG and complement to phagocytize encapsulated bacteria. This cooperativity
      between multiple receptors often changes the apparent affinity of the receptors
      for their ligand. Consequently the physiology of these receptors is altered.
      Fibronectin ligation, for example, results in the internalization of C3b-coated
      particles by the CR1. The second concept concerns the transduction of specific
      cellular signals following receptor ligation. Often, the receptor to which a
      microbe binds orchestrates many of the subsequent intracellular events during
      phagocytosis by transducing specific cellular signals. Some receptors, for
      example the mannose and Fc gamma-receptors, are particularly well suited to
      direct particles to phagolysosomes and trigger a respiratory burst, whereas other
      receptors, for example the CR1, may not. Indeed, from this perspective, one can
      view the immune response as being designed to target microbes preferentially to
      those receptors on phagocytic cells capable of making the appropriate cellular
      responses. In the case of leishmania, phagocytosis mediated by the Fc gamma
      receptors leads to parasite killing even by resident macrophages, while
      complement-mediated phagocytosis leads to parasite survival.

PMID- 7504532
TI  - [In patients with atopy the anesthesia risk is heightened--fact or fiction?].

PMID- 7504533
TI  - Enzymatic and immunohistochemical evaluation of tyrosine phosphorylation in
      breast cancer specimens.
AB  - Using a synthetic peptide substrate, tyrosine protein kinase (TPK) activity was
      measured in 21 tumors from patients with histologically confirmed breast cancer
      and in five normal breast tissues from patients undergoing reduction mammoplasty.
      In 20 of 21 cancer specimens, tumor was available to assess phosphotyrosine (PT)
      immunohistochemically. Breast cancer specimens possessed significantly more TPK
      activity than normal breast tissues (Cancer = 43.9 +/- 3.1 pm/mg protein/min,
      [Mean +/- S.E.M.]; Normal = 3.4 +/- 0.9, p < 0.001). TPK activity was higher in
      the clinically more aggressive infiltrating ductal cancers compared to the less
      aggressive intraductal cancers (Infiltrating = 55.9 +/- 5.8; Intraductal = 17.2
      +/- 3.4, p < 0.01). TPK activity in tumors with both infiltrating and intraductal
      histology was intermediate (34.0 +/- 7.2). Significant correlation existed
      between membrane TPK enzymatic activity and PT expression by
      immunohistochemistry. There was no relationship between estrogen or progesterone
      receptor status and TPK activity or PT; however, TPK activity from node negative
      breast cancer tissue was significantly less than from node positive specimens (p
      < 0.01). We conclude that breast cancer specimens possess elevated amounts of TPK
      which correlate with PT expression, and that increased tyrosine phosphorylation
      appears to correlate with the biologic aggressiveness of the malignant tumor.

PMID- 7504534
TI  - Treatment of clozapine- and molindone-induced agranulocytosis with granulocyte
      colony-stimulating factor.
AB  - OBJECTIVE: To report a case of clozapine- and molindone-induced agranulocytosis
      and to discuss treatment using filgrastim, a granulocyte colony-stimulating
      factor. CASE SUMMARY: A 64-year-old woman who had been on long-term clozapine
      therapy for schizophrenia was hospitalized with presumed drug-induced
      agranulocytosis. She had also been on short-term molindone therapy. A bone marrow
      biopsy and the initial white blood cell (WBC) count were consistent with drug
      induced agranulocytosis. Following seven days of treatment with subcutaneous
      filgrastim 300 micrograms/d, her absolute neutrophil count was above 500 x
      10(6)/L. DISCUSSION: Reports in the literature discussing antipsychotic drug
      induced agranulocytosis are reviewed. A relationship between treatment with
      filgrastim and WBC response is postulated. CONCLUSIONS: Filgrastim may be useful
      in ameliorating the effects of clozapine- and molindone-induced agranulocytosis.

PMID- 7504535
TI  - Halothane vasodilation and nitric oxide in rat pial vessels.
AB  - We investigated whether halothane (HAL), administered via cerebral cortical
      suffusion at concentrations of 1, 2, and 3%, could induce cerebral microvascular
      dilatation in vivo and whether the vasodilatory response was dependent on nitric
      oxide (NO) synthesis. The studies were performed using N2O/fentanyl-anesthetized,
      paralyzed, and mechanically ventilated rats. A closed cranial window and an
      intravital microscopy technique were employed. This system permitted the
      controlled delivery of various vasoactive agents in an artificial cerebrospinal
      fluid (aCSF) solution and the measurement of diameters of pial arterioles and
      venules. Each experiment included evaluations of (a) the direct smooth muscle
      relaxing action of NO, using sodium nitroprusside (SNP), and (b) the capacity for
      generation and release of endogenous NO, using adenosine diphosphate (ADP).
      Following confirmation of an intact NO-relaxing and generating capacity, HAL (in
      aCSF) was suffused at increasing concentrations. Nitric oxide synthase (NOS)
      inhibition was established with topical nitro-L-arginine (L-NA) or its methyl
      ester (L-NAME) and the above sequence repeated. The results for rats treated with
      L-NA (n = 5) or L-NAME (n = 5) were analyzed separately and as a combined group.
      No significant differences in vascular responses were observed when comparing the
      two groups. Initially, both SNP and ADP produced significant diameter increases
      (all groupings) in arterioles (14-28% change) and venules (14-25% change). For
      all groups, suffusions of 1 to 3% HAL produced arteriolar dilation, ranging from
      a 10 to 25% increase over baseline diameter. A statistically significant dose
      dependency was only observed with the combined data.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7504536
TI  - [Laser therapy and tube implantation for palliative treatment of inoperable
      esophageal and cardia cancer].
AB  - Laser photocoagulation and intubation are effective measures for palliation of
      the unresectable esophago-cardial malignancy. Laser therapy is especially useful
      for short strictures and noncircular and proximal lesions. Intubation usually
      leads to a rapid relief of dysphagia especially in patients with extensive tumor
      involvement of the esophagus; for esophago-bronchial fistula special tubes are
      available. By using the newly developed metal endoprotheses, the higher
      complication rates of the plastic tubes as compared with laser therapy could
      probably be decreased. Nowadays, endoscopic palliation of esophageal carcinoma is
      usually applied as part of multimodal oncological treatment concepts.

PMID- 7504537
TI  - Purification of an active TATA-binding protein-containing factor using a
      monoclonal antibody that recognizes the human TATA-binding protein.
AB  - The human TATA-binding protein was expressed in Escherichia coli as a fusion with
      an N-terminal hexahistidine sequence, partially purified, and used to raise
      monoclonal antibodies. More than 50 hybridoma clones producing antibodies that
      reacted in immunoblot assays with HeLa cell TATA-binding protein and its
      bacterially synthesized derivative were identified. All antibodies examined
      recognized epitopes within the N-terminal 159 amino acids of the human TATA
      binding protein. Further characterization of one monoclonal antibody, MTBP-6,
      established that it immunoprecipitates both native HeLa cell TATA-binding protein
      and TATA-binding protein extracted from cells in the presence of 0.5% SDS.
      Antibody MTBP-6 immunoprecipitates of native, human cell TATA-binding protein
      contained the TATA-binding protein and additional polypeptides.
      Immunoprecipitation of both the TATA-binding protein and several additional
      polypeptides was specifically blocked by bacterially synthesized, hexahistidine
      tagged TATA-binding protein, suggesting that MTBP-6 can efficiently recognize the
      TATA-binding protein in TFIID and other complexes. Consistent with this
      conclusion, immunoaffinity chromatography on antibody MTBP-6 permitted
      purification, in active form, of a TATA-binding protein-containing factor
      required for transcription by RNA polymerase III. These properties suggest that
      MTBP-6 will be a useful reagent for the purification and characterization of the
      multiple TBP-containing complexes present in human cells.

PMID- 7504538
TI  - Isolation and characterization of three recombinant human granulocyte colony
      stimulating factor His-->Gln isoforms produced in Escherichia coli.
AB  - This report demonstrates that three variant isoforms of recombinant methionyl
      human granulocyte colony stimulating factor are present in small quantities in
      the crude preparation solubilized from Escherichia coli inclusion bodies. These
      isoforms were separated from the main form of the factor during purification and
      further isolated by a series of cationic exchange chromatographic separations.
      They exhibit full in vitro biological activity and have slightly lower pI's.
      Structural characterization of the intact proteins and their isolated peptides by
      sequence determination and mass spectrometric analysis revealed that they are
      methionyl granulocyte colony stimulating factors having a His-->Gln replacement
      at sequence position 53, 157, or 171, respectively. The specific His-->Gln change
      suggests the occurrence of mistranslation during protein synthesis. These variant
      forms are chromatographically separable during purification and are not
      detectable in the final purified form of the factor.

PMID- 7504539
TI  - Kidney granuloma in Whipple's disease.

PMID- 7504541
TI  - Expression of human endogenous retrovirus (HERV-K) in chronic myeloid leukemia.
AB  - We have previously demonstrated the presence of a reverse transcriptase-like
      enzyme in retroviral particles from patients with essential thrombocythemia,
      polycythemia vera, and chronic myelogenous leukemia. It was subsequently shown
      that the human genome contains 50 copies of HERV-K. HERV-K is a human endogenous
      class I retroviral element that contains gag, pol, and env open reading frames.
      Using both reverse transcriptase-polymerase chain reaction and ribonuclease
      protection assays, it is demonstrated that the HERV-K pol is expressed in human
      blood leukocytes. The data indicates that this expression is restricted in CML
      white cells and is the result of gene regulation.

PMID- 7504540
TI  - Pertussis immunisation and serious acute neurological illnesses in children.
AB  - OBJECTIVE: To determine long term outcome in children who had a severe acute
      neurological illness in early childhood associated with pertussis immunisation.
      DESIGN: Follow up study of cases and matched controls. SETTING: Assessment of
      children at home and at school throughout Britain. SUBJECTS: Children recruited
      into the national childhood encephalopathy study in 1976-9 were followed up, with
      one of their two original matched controls, in 1986-9. MAIN OUTCOME MEASURES:
      Performance in educational attainment tests; behaviour problems reported by
      teachers and parents; continuing convulsions; evidence of other neurological or
      physical dysfunction. RESULTS: Over 80% of cases and controls were traced. Case
      children were significantly more likely than controls to have died or to have
      some form of educational, behavioural, neurological, or physical dysfunction a
      decade after their illness. The prevalence of one or more of these adverse
      outcomes in case children who had been immunised with diphtheria, tetanus, and
      pertussis vaccine within seven days before onset of their original illness was
      similar to that in case children who had not been immunised recently. The
      relative risk for recent diphtheria, tetanus, and pertussis immunisation in
      children who had died or had any dysfunction in comparison with controls was 5.5
      (95% confidence interval 1.6 to 23.7). However, the number of cases associated
      with vaccine (12) was extremely small and statistically vulnerable, and other
      possible agents or predisposing factors could not be excluded. CONCLUSIONS:
      Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated
      with the development of severe acute neurological illnesses that can have serious
      sequelae. Some cases may occur by chance or have other causes. The role of
      pertussis vaccine as a prime or concomitant factor in the aetiology of these
      illnesses cannot be determined in any individual case. The balance of possible
      risk against known benefits from pertussis immunisation supports continued use of
      the vaccine.

PMID- 7504542
TI  - Tyrosine phosphorylated proteins in chronic myelogenous leukemia.
AB  - An aberrantly expressed and highly active abl tyrosine kinase (p210bcr-abl)
      appears critical for the development and pathogenesis of chronic myelogenous
      leukemia (CML). CML cells and cell lines each displayed a similar spectrum of
      phosphotyrosyl proteins. Analysis of these proteins by glycerol-gradient
      ultracentrifugation showed that many apparently existed as multimeric complexes.
      Confirming this, several of these proteins co-immunoprecipitated, along with the
      p210bcr-abl, with antibody to abl. Included were co-precipitating proteins
      identified as the p120 ras GTPase-activating protein (GAP) and the p62 protein
      that binds both to GAP and to a number of other tyrosine-phosphorylated proteins
      having peptide regions homologous to the second domain of src. Because p62, ras
      GAP and ras are involved in growth-factor and oncogene activation of cells, this
      pathway may also play an important role in CML.

PMID- 7504544
TI  - Potential mechanisms of action of interferon-alpha in CML.
AB  - Treatment with interferon-alpha (IFN-alpha) adequately controls the leukemic cell
      mass in the majority of newly diagnosed patients with chronic myeloid leukemia
      (CML). However, the degree of response ranges from no 'hematologic' response to
      complete suppression of the leukemic clone. The mechanism(s) by which IFN-alpha
      elicits these responses is unknown, but in vitro studies have indicated that IFN
      alpha might function by (1) selective toxicity against the leukemic clone, (2)
      enhancement of 'immune' regulation, and (3) modulation of bone marrow
      microenvironmental regulation of hematopoiesis. Using in vitro clonogenic assays
      we were unable to demonstrate that IFN-alpha selectively inhibited the
      proliferation of CML progenitor cells. We also found no difference in the
      expression of LFA-3 on normal or CML CD34+ cells. However, by panning and co
      culturing hematopoietic cells on monolayers of bone marrow stromal cells, grown
      with and without IFN-alpha, we found that IFN-alpha enhanced the adhesion of CML
      progenitors to stromal cells, whereas adhesion by normal progenitor cells was
      essentially unaffected. This enhanced adhesion by CML progenitor cells was
      associated with a reduction in neuraminic acid levels in the extracellular matrix
      overlying stromal cells. Therefore, it is possible that one of the mechanisms by
      which IFN-alpha exerts its regulatory effect on the leukemic clone is through
      enhancement of hematopoietic cell-microenvironmental cell interactions.

PMID- 7504543
TI  - Potential therapeutic applications of antisense oligodeoxynucleotides in the
      treatment of chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) cell growth may be inhibited by exposure to
      antisense (AS) oligodeoxynucleotides (ODN). Our initial studies targeted the c
      myb protooncogene and were carried out on cells derived from patients in CML
      blast crisis. Subsequently, we extended these studies to cells isolated from
      patients in chronic disease phase. We found that c-myb AS ODN inhibited growth of
      CML CFU-GM in a dose dependent, sequence specific manner in approximately 75% of
      cases evaluated. Bcr-abl expression was either greatly decreased or nondetectable
      in the residual colonies and no residual leukemic CFU were demonstrable upon re
      plating of treated cells. AS ODN that target the c-kit protooncogene also inhibit
      CML CFU and lead to downregulation of bcr-abl in responding cells in
      approximately 50% of cases. Therefore, AS ODN may prove to be useful purging
      agents. Most recently, we have treated SCID mice engrafted with bcr-abl
      expressing human K562 cell leukemia with phosphorothioate modified AS ODN. We
      have found that treated mice survive three to eight times longer than their
      untreated or sense treated controls. In aggregate, these results suggest that AS
      ODN may prove useful for both ex vivo and in vivo treatment of patients with CML.

PMID- 7504545
TI  - Peripheral blood stem cell autografts in CML.
AB  - The treatment of patients with CML in chronic phase by high dose chemotherapy
      followed by transfusion of autologous haemopoietic stem cells collected and
      cryopreserved previously may theoretically prolong survival. This benefit could
      result from reducing the number of leukaemia stem cells at risk for
      transformation or by partial re-establishment of Ph-negative haematopoiesis. In
      practice some patients achieve partial Ph-negative haematopoiesis after
      autografting but most patients have entirely Ph-positive haematopoiesis by one
      year after autografting. Results may be improved if methods to favour
      reconstitution with Ph-negative haematopoiesis can be perfected.

PMID- 7504546
TI  - Detection of tumor-specific antigens in Philadelphia chromosome positive
      leukemias.
AB  - In chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) the Ph1
      chromosome (22q-) is the most frequent chromosomal aberration encountered. At the
      molecular level the c-abl gene from chr. 9 is translocated to the bcr gene on
      chr. 22. As a result, a chimeric bcr-abl gene is generated, which encodes
      chimeric proteins. Since these proteins are only expressed in Ph1 positive cells,
      they are per definition tumor-specific. In this report we describe the reactivity
      of polyvalent antisera raised against synthetic peptides corresponding to the
      tumor-specific bcr-abl junctions. Native chimeric proteins were specifically
      recognized by these junction-specific antisera. Therefore we conclude that the
      bcr-abl junctions are antigenically exposed on the chimeric proteins. We discuss
      the relevance of these antisera for CML and ALL diagnosis.

PMID- 7504547
TI  - Proliferative advantage rather than classical drug resistance as the cause of
      treatment failure in chronic myelogenous leukemia.
AB  - This presentation discusses the role that proliferative advantage plays in making
      both the chronic and blastic phases of CML resistant to therapy. A case is made
      for the addition of "regrowth" inhibitors between courses of chemotherapy as a
      means of increasing the efficacy of therapy by suppressing or reducing the
      proliferative advantage that the target cells enjoy over those cells which one
      would like to repopulate the hematopoietic system.

PMID- 7504548
TI  - Identification of a new polymorphism in the human proteolipid protein gene.
AB  - A polymorphism in the gene for proteolipid protein has been identified, using
      amplification by the polymerase chain reaction, restriction enzyme digestion, and
      fragment separation by polyacrylamide gel electrophoresis. The polymorphism is
      located in the transcribed 3'-untranslated region, a region with potential
      regulatory signals. The mutation consists of a single base pair insertion into a
      Hae III restriction site, producing a larger rare fragment of 409 bp as compared
      with the more frequent 325 bp fragment. The gene for proteolipid protein is on
      the X chromosome; thus the males are hemizygous for the rare allele and the
      females are heterozygous carriers. The polymorphism occurs with a frequency of
      0.046 in a population of European origin and also has a rare frequency in
      multiple sclerosis patients.

PMID- 7504549
TI  - Myelin basic protein domains involved in the interaction with actin.
AB  - A fluorescence assay was used to measure the interaction of myelin basic protein
      (MBP) with monomeric actin labeled with a fluorescent compound (IAEDANS). The
      complex actin-IAEDANS increase the fluorescence in presence of MBP. The
      enhancement of the fluorescence has a sigmoidal dependence on the concentration
      of MBP and the fluorescence maximum is reached at a MBP:actin molar ratio of
      1:20. The fluorescence maximum in absence of Ca2+ and ATP is 4 times lower than
      that in their presence although it is reached at the same MBP:actin molar ratio.
      Similar behavior is observed when synapsin replaces MBP, while acetylated MBP and
      bovine serum albumin fail to induce any fluorescence change. To define possible
      interacting domains on MBP involved in the actin-MBP interaction, experiments
      were performed using MBP-derived peptides obtained under controlled proteolysis
      of the whole molecule. The fluorescence changes induced by the different peptides
      depend on their location in the native protein and can not be explained simply by
      a difference in the net charge of the peptides. The results suggest that two
      sites are involved in the interaction. A Ca2+/ATP-dependent site located in the
      amino-terminal region (peptide 1-44) and a Ca2+/ATP-independent one near the
      carboxyl terminus of the MBP molecule. The actin-MBP interaction was also
      observed using immunoblot and ELISA techniques.

PMID- 7504550
TI  - Calculation of protein backbone geometry from alpha-carbon coordinates based on
      peptide-group dipole alignment.
AB  - An algorithm is proposed for the conversion of a virtual-bond polypeptide chain
      (connected C alpha atoms) to an all-atom backbone, based on determining the most
      extensive hydrogen-bond network between the peptide groups of the backbone, while
      maintaining all of the backbone atoms in energetically feasible conformations.
      Hydrogen bonding is represented by aligning the peptide-group dipoles. These
      peptide groups are not contiguous in the amino acid sequence. The first dipoles
      to be aligned are those that are both sufficiently close in space to be arranged
      in approximately linear arrays termed dipole paths. The criteria used in the
      construction of dipole paths are: to assure good alignment of the greatest
      possible number of dipoles that are close in space; to optimize the electrostatic
      interactions between the dipoles that belong to different paths close in space;
      and to avoid locally unfavorable amino acid residue conformations. The equations
      for dipole alignment are solved separately for each path, and then the remaining
      single dipoles are aligned optimally with the electrostatic field from the
      dipoles that belong to the dipole-path network. A least-squares minimizer is used
      to keep the geometry of the alpha-carbon trace of the resulting backbone close to
      that of the input virtual-bond chain. This procedure is sufficient to convert the
      virtual-bond chain to a real chain; in applications to real systems, however, the
      final structure is obtained by minimizing the total ECEPP/2 (empirical
      conformational energy program for peptides) energy of the system, starting from
      the geometry resulting from the solution of the alignment equations. When applied
      to model alpha-helical and beta-sheet structures, the algorithm, followed by the
      ECEPP/2 energy minimization, resulted in an energy and backbone geometry
      characteristic of these alpha-helical and beta-sheet structures. Application to
      the alpha-carbon trace of the backbone of the crystallographic 5PTI structure of
      bovine pancreatic trypsin inhibitor, followed by ECEPP/2 energy minimization with
      C alpha-distance constraints, led to a structure with almost as low energy and
      root mean square deviation as the ECEPP/2 geometry analog of 5PTI, the best
      agreement between the crystal and reconstructed backbone being observed for the
      residues involved in the dipole-path network.

PMID- 7504551
TI  - Laser prostatectomy: our initial experience of a technique in evolution.
AB  - Recently great interest has been generated in alternatives to transurethral
      resection for benign prostatic hyperplasia. Lasers are currently being assessed,
      but marketing has for the moment outstripped basic science. A cystoscopic
      approach was used delivering Nd:YAG or KTP laser energy via forward and
      sidefiring fibers and contact tip devices in 51 patients. The sidefiring device
      is intended to coagulate a volume of prostate that subsequently sloughs, leaving
      a cavity. Treatment of the apical and middle lobe tissue using this technique was
      unsatisfactory. A further disadvantage was the interval between treatment and
      improvement in urine flow, which was approximately 6 weeks. The use of temporary
      prostatic stents has helped to overcome this delay in treatment effect.
      Encouraging early results have been achieved using forward-firing fibers to treat
      apical and middle lobe tissue. The use of contact tip devices to perform
      bloodless prostatotomies in combination with sidefire or bare fiber has also
      proved useful. Laser prostatectomy is an exciting field with considerable
      potential but remains in the developmental stage.

PMID- 7504552
TI  - Non-invasive liposome-mediated gene delivery can correct the ion transport defect
      in cystic fibrosis mutant mice.
AB  - We report gene transfer to the Edinburgh insertional mutant mouse (cf/cf),
      delivering CFTR cDNA-liposome complexes into the airways by nebulization. We show
      full restoration of cAMP related chloride responses in some animals and
      demonstrate, in the same tissues, human CFTR cDNA expression. Overall, a range of
      correction was seen with restoration of about 50% of the deficit between wild
      type mice and untreated cf/cf controls. We report modest correction in the
      intestinal tract following direct instillation and provide initial encouraging
      safety data for both the respiratory and intestinal tract following the liposome
      mediated gene delivery. The non-viral nature and potentially lower immunogenicity
      of DNA-liposomes suggest that this may offer a therapeutic alternative to
      adenoviral therapies.

PMID- 7504553
TI  - Identification of the genetic locus for keratosis palmaris et plantaris on
      chromosome 17 near the RARA and keratin type I genes.
AB  - Familial keratosis palmaris et plantaris (KPPF) is characterized by extreme
      keratinization and desquamation of the skin of the palmar and plantar surfaces of
      the hands and feet. We have mapped the causative genetic defect to an 8 cM
      interval on 17q12-24 in or close to the acidic keratin (type I) gene cluster. We
      show that KPPF co-segregates with a rare, high molecular weight allele of an
      insertion-deletion polymorphism in the C-terminal coding region of the keratin 10
      gene (Z = 8.36 at theta = 0.00) and segrates as a true autosomal dominant trait.
      Some pedigrees with familial hyperkeratosis of the palms and soles have co
      inherited diseases such as congenital malformations and familial cancers. Our
      analysis provide a region which should be investigated for contiguous gene
      syndromes in such pedigrees.

PMID- 7504554
TI  - Effect of transurethral resection of the prostate on detrusor instability and
      urge incontinence in elderly males.
AB  - Detrusor instability is common in men with evidence of outflow obstruction due to
      benign prostatic hypertrophy and typically reverses in about two thirds of
      patients after transurethral resection of the prostate (TURP). It is also common
      among the elderly without outflow obstruction and may lead to urge incontinence.
      To determine whether TURP has an effect on detrusor instability and urge
      incontinence in elderly men, or whether these abnormalities are due to other age
      associated changes, 12 males (mean age 80 years) with urge incontinence or
      frequency and urgency of micturition, and symptomatic benign prostatic
      hypertrophy, were studied by 24-hour monitoring of incontinence and
      videourodynamic examination, before and after TURP; 7/12 patients were
      significantly cognitively impaired. Preoperatively, all patients showed detrusor
      instability, which reversed postoperatively in only one patient, a significantly
      smaller proportion than that consistently reported in younger patients.
      Preoperatively, 11/12 patients were incontinent. After TURP, 8/11 patients had an
      improvement in the amount of incontinence, by up to 458 g in 24 hours. Those who
      improved had been urodynamically more severely obstructed preoperatively. Those
      with the most improvement were also cognitively impaired. We conclude that, in
      the geriatric population, detrusor instability and urge incontinence may be the
      result of age-associated changes and not secondary to obstruction. Detrusor
      instability is likely to persist following TURP. Preoperative urodynamic
      assessment of obstruction in the incontinent male with benign prostatic
      hypertrophy may be useful since the severity of incontinence responds well to
      TURP if there is marked obstruction. Cognitive impairment should not be a
      deterrent to operation.

PMID- 7504555
TI  - DIP: a member of the MIP family of membrane proteins that is expressed in mature
      seeds and dark-grown seedlings of Antirrhinum majus.
AB  - DiP, a gene from Antirrhinum majus, which encodes a protein with striking
      homology to other integral membrane proteins, was cloned. The gene was
      specifically expressed in mature seeds and during seedling germination,
      particularly in cotyledons of seedlings grown in the dark. The deduced product,
      called DiP, for dark intrinsic protein, shows strong homology with the MIP family
      of channel transporters which include; the bovine major intrinsic protein (MIP),
      the Escherichia coli glycerol facilitator (GIpF), the peribacteroid nodulin-26
      (Nod26), and the tonoplast protein from kidney bean (TIP). DiP is most similar to
      other plant members of this family, and in particular to the tobacco protein
      TobRB7 which is expressed specifically in roots. However, the expression pattern
      of diP suggests that its product is functionally more similar to the tonoplast
      intrinsic protein from kidney bean since it is most highly expressed in the
      cotyledons of germinating seedlings, before the cells undergo expansion growth
      and become photosynthetic.

PMID- 7504556
TI  - [Anatomo-functional changes in the prostate and seminal vesicles with aging].
AB  - The anatomo-functional modifications of the prostate and the seminal pathways
      during the genital apparatus aging, (prostatic hyperplasia and hypotrophy of the
      seminal pathways and testis), are caused by hormonal modifications (inconstant
      increase of the gonadotropins LH-FSH, decrease of the peripheric utilization of
      testosterone, alterations of the adrenal secretion), by anatomical involutions
      (degenerations of the glandular, stromal and vascular components).

PMID- 7504557
TI  - [Andrologic problems in benign prostatic hyperplasia].
AB  - Retrograde ejaculation is observed after surgical treatment of B.P.H. in the
      majority of patients; erectile failure may follow these procedures in 10-20% of
      cases. Post-prostatectomy impotence is not depending on surgical technique and
      probably occurs as a consequence of venous leakage due to traumatic injury of the
      nervi erigentes at the prostatic apex. Pathological factors also play an
      important role as it is shown by the efficacy of preoperative exploration in
      reducing the incidence of this complications. It is advisable to include potency
      problems in the informed consent to be signed by the patient before any kind of
      prostatic surgery.

PMID- 7504558
TI  - [Treatment of urinary incontinence in the patient operated on for benign
      prostatic hyperplasia].
AB  - A potential complication of prostatic adenomectomy and TURP is urinary
      incontinence. The incidence of this problem ranges from 0.1 to 1%. we reviewed
      our experience with 15 patients who were incontinent between 10 to 24 months
      after prostatectomy. We treated these patients with bladder training. At first,
      patients were evaluated for the type and extent of incontinence. Perineal
      exercise were taught in detail, tested for their correct use via simultaneous and
      abdominal examination. Patients were evaluated weekly for compliance. No
      pharmaceutical agents were used. All the 15 patients improved in the number of
      incontinence episodes 5 patients achieved total continence, while only one showed
      a little change. We conclude that patients who are incontinent after
      prostatectomy can improve with a well-done behavioral training program.

PMID- 7504559
TI  - Altered immunoglobulin A (IgA-1) levels in patients with advanced colorectal
      adenocarcinoma presenting with normal preoperative levels of carcinoembryonic
      antigen (CEA).
AB  - We investigated the value of serum IgA-1 as a complementary tumour marker to
      carcinoembryonic antigen (CEA) in the monitoring of the postoperative follow-up
      of 19 patients with advanced colorectal carcinoma presenting with normal levels
      of CEA. Mean follow-up period was 14 months (range 2-72 months). Mean number of
      serum specimens was 5 (range 2-9). IgA-1 assay employed rabbit antihuman IgA for
      binding IgA-1 from patient's serum and peanut agglutinin to detect the IgA-1 O
      glycosidic structure. Ten patients developed distant metastases while nine
      patients had locoregional recurrence. All 19 patients had generally persistent
      elevation of serum IgA-1 throughout the follow-up period while serum CEA levels
      were subsequently elevated in only 10 patients. IgA-1 predicted recurrence with
      an average lead time of 8 months (range 1-19 months). On the other hand, mean lag
      time for CEA was 12 months (range 6-50 months). The data indicate the clinical
      utility of serum IgA-1 as a potential complementary tumour marker to CEA in the
      monitoring of the postoperative course of this particular subset of colorectal
      cancer patients.

PMID- 7504560
TI  - Endoscopic laser treatment for palliation of colorectal adenocarcinoma.
AB  - Fifty-three patients were treated for palliation with endoscopic neodymium
      yttrium aluminum garnet (Nd:YAG) laser for colorectal carcinoma at Roswell Park
      Cancer Institute. There were 25 females and 28 males. The mean age of the
      patients was 76 years. Thirty-eight tumours were primary and 15 recurrent. The
      level of the lesions from the anal verge ranged from 2 to 50 cm, with a mean of
      10 cm. Eighty-four percent of the lesions were rectal carcinomas within 15 cm of
      the anal verge. Lesion length ranged from 1.5 to 12 cm with a mean of 5 cm. The
      number of laser treatments ranged from 1 to 17 with a mean of 3. The duration of
      treatments ranged from 25 to 90 min with a mean of 35 min. The mean number of
      joules per treatment was 5093. Eight patients (15%) developed complications.
      There were no mortalities. The success rate for treating bleeding, the most
      frequent presenting symptom, was 93%. The overall success rate of patients
      improved by laser treatment was 79%. Patients who were improved by therapy had a
      median survival of 18 months versus those not improved who had a median survival
      of 3 months (P = 0.01). The use of the Nd:YAG laser for palliative treatment of
      patients with colorectal carcinoma is safe, effective and associated with no
      mortality.

PMID- 7504561
TI  - Relief of metastatic biliary obstruction by stent placement: is it worthwhile?
AB  - Twenty-one patients undergoing stent placement for extra-hepatic biliary
      obstruction by metastatic disease were reviewed. Primary tumours (colorectal 8,
      stomach 4, breast 2, ovary 2, others 5) had been diagnosed 13 months (median)
      before presentation with bile duct obstruction, which was at the porta hepatis or
      common hepatic duct in 14 patients and in the common bile duct in seven.
      Endoscopic stent placement was achieved in 14 out of 20 patients in whom it was
      attempted. A percutaneous trans-hepatic procedure was necessary in five patients.
      Two patients could not be stented. Median survival was 5 months (range 1 month to
      6 years) in patients stented successfully but only 1 month (2 weeks to 3 months)
      in unsuccessful cases (P < 0.01). Nine patients survived more than 4 months.
      Patients with proximal obstruction fared less well than those with distal
      obstruction; they required more procedures and survived for shorter periods
      (median 1 month versus 5 months, P < 0.05). Worthwhile palliation is afforded to
      almost half these patients by endoscopic stent placement and individual patients
      may achieve prolonged, symptom-free survival.

PMID- 7504562
TI  - Relief of malignant obstructive jaundice.

PMID- 7504563
TI  - CD44 participates in the adhesion of human colorectal carcinoma cells to laminin
      and type IV collagen.
AB  - CD44 is a cellular adhesion molecule expressed in many different types of cells
      that may be a receptor for hyaluronic acid, laminin, collagen or fibronectin. In
      this study, we determined whether CD44 participated in the adhesion of three
      human colorectal carcinoma cell lines (KM-12c, CCL 188 and MIP-101) to laminin,
      collagen and hyaluronic acid. All lines were positive for the epithelial form of
      CD44 (CD44E) with a molecular weight of approximately 160 kD. All of them bound
      significantly to laminin and type IV collagen but not to hyaluronic acid in a
      solid phase adhesion assay. Three monoclonal antibodies to CD44 (Hermes 1, Hermes
      3 and J173) significantly blocked the binding of colorectal carcinoma lines to
      laminin and collagen whereas another antibody to CD44 (50B4) bound to cells but
      did not inhibit adhesion. Only Hermes 1 completely abolished the binding to
      hyaluronic acid by a human B lymphoblastoid cell line, JY, that expressed the 90
      kD haematopoietic form of CD44. Soluble hyaluronate inhibited the adhesion of JY
      cells to solid phase hyaluronate but did not inhibit adhesion to laminin and
      collagen by the colorectal carcinoma lines. Thus, (a) CD44E participates in the
      adhesion of colorectal carcinoma cells to laminin and type IV collagen and (b)
      the binding site for laminin and collagen on CD44E is different from the site for
      hyaluronic acid.

PMID- 7504564
TI  - Laparoscopic cholecyst-jejunostomy and gastroenterostomy for malignant disease.
AB  - The technique of videolaparoscopic surgical bypass for malignant obstruction of
      the distal common bile duct and duodenum is described as it has evolved since
      1991. The techniques available include anastomosis of jejunum to the gallbladder
      and stomach by suture, staples or a combination of the two techniques. The
      present criteria for patient selection for these palliative approaches, alone or
      in combination with ERCP stenting, are discussed. Early clinical experience in
      several small series of patients treated by this laparoscopic approach suggests
      rapid recovery will be added to the proven reliability of these open palliative
      bypass techniques.

PMID- 7504565
TI  - An association between low levels of 5-HIAA and HVA in cerebrospinal fluid and
      early mortality in a diagnostically mixed psychiatric sample.
AB  - We followed up a sample of psychiatric patients (diagnoses predominantly
      schizophrenia and depression) who had participated in in-patient studies of their
      CSF over the past 15 years. The status of 73 former patients was confirmed, of
      whom 12 had died. Seven of these patients died at age < or = 40, largely of
      suicide, homicide, or accidental causes. These seven patients had significantly
      lower CSF 5-HIAA and HVA than living control patients. There were significant
      direct correlations between age at death and both CSF 5-HIAA and HVA in the
      deceased patients. The results offer support for CSF monoamine metabolites
      relating to early death in a diagnostically diverse sample of psychiatric
      patients.

PMID- 7504566
TI  - Native and graft pancreatitis following combined pancreas-renal transplantation.
AB  - Ten patients who had undergone whole-organ pancreas transplantation and
      pancreatoduodenocystostomy from a total of 60 simultaneous cadaveric kidney
      pancreas transplants met the criteria for graft pancreatitis. This condition is
      clearly different from acute rejection on the basis of marked hyperamylasaemia
      and significant local findings over the allograft. Graft rejection was the cause
      of graft loss in one of the patients; eight are alive, seven with a functioning
      graft 61, 30, 27, 25, 21, 18 and 14 months after transplantation. Two patients
      died: one from severe graft pancreatitis and the other from cytomegalovirus
      infection. Bladder drainage with or without antibiotics has been the most common
      therapy, based on the theory that damage is caused by duodenal content and
      infected urine reflux. To prevent graft loss, antiviral treatment should be given
      when pancreatitis due to cytomegalovirus is suspected or diagnosed. Two patients
      with native pancreatitis are also described; the disease was severe and surgery
      was required in both cases. The pancreas grafts have now been functioning for 2
      years 7 months and 2 years 10 months respectively.

PMID- 7504567
TI  - Changing trends in the management of extrahepatic cholangiocarcinoma.
AB  - A series of 107 patients with cholangiocarcinoma diagnosed between January 1980
      and December 1991 is reported. Changing patterns of investigation and treatment
      in the periods 1980-1985 and 1986-1991 are analysed. There was a decrease in the
      use of percutaneous transhepatic cholangiography in the second period (86 versus
      51 per cent of patients) but increased use of endoscopic retrograde
      cholangiography (19 versus 71 per cent) and computed tomography (8 versus 59 per
      cent). The overall resectability rate (17 per cent) was similar to those of other
      reported series but greater in the second period (8 versus 21 per cent).
      Palliation by endoscopic and percutaneous stenting was associated with a high
      incidence of recurrent cholangitis (55 per cent) and jaundice (35 per cent).
      During the second 6-year period, more effective palliation was achieved by
      segment III cholangiojejunostomy with a lower incidence of recurrent cholangitis
      (19 per cent) and jaundice (19 per cent). Overall prognosis for patients with
      this condition is grim and efforts must usually be aimed at providing the most
      appropriate palliation.

PMID- 7504568
TI  - Possible role of the N-terminus of substance P in kainic acid-induced toxicity in
      rats.
AB  - Subcutaneously administered kainic acid (KA) in the rat results in brain damage
      accompanied by a behavioral response characterized by wet dog shakes (WDS),
      seizures and brain damage, an effect that is potentiated by opioids. Based on the
      potentiative effect of the N-terminus of substance P (SP) on the ability of KA to
      induce behavioral responses in mice, we tested the hypothesis that the N-terminus
      of SP also plays a role in KA-induced neurotoxicity in rats. Pretreatment i.p.
      with 1 or 10 nmol of SP(1-7), a major N-terminal metabolite of the undecapeptide
      SP, 15 min before administration of 12 mg/kg of KA potentiated the incidence of
      WDS. In contrast, after administration of 1 nmol of [D-Pro2, D-Phe7]SP(1-7) (D
      SP(1-7)), the D-isomer of SP(1-7) and a substance P N-terminal antagonist, the
      intensity of KA-induced WDS was no different from those in either the KA- or
      saline-injected rats. However, pretreatment with D-SP(1-7) completely blocked the
      potentiative effect of SP(1-7) on the KA-induced WDS. While the severity of KA
      induced lesions was not significantly altered by pretreatment with 1 nmol of SP(1
      7), the effect of KA was not significantly different from that in control rats
      when administered with 1 nmol of D-SP(1-7). These results suggest a possible
      involvement of endogenous SP N-terminal activity in the effects following
      subcutaneous (s.c.) administration of KA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504569
TI  - Dihydrostreptomycin modifies adaptation and blocks the mechano-electric
      transducer in chick cochlear hair cells.
AB  - Block of the mechano-electric transduction (MET) channel by dihydrostreptomycin
      (DHSM) and its effects on adaptation were investigated in dissociated cochlear
      hair cells of the chick with a whole-cell patch-electrode voltage clamp
      technique. DHSM reversibly blocked the MET channel in a dose- and voltage
      dependent manner. At -50 mV, DHSM blocked the MET channel with a Hill coefficient
      of approximately 1 and a dissociation constant (Kd) of 2 x 10(-5) M. Rate
      constants for the DHSM to bind and to unbind to and from the channel were
      estimated, and could be larger than 5 x 10(7) M-1.s-1 and 1 x 10(3) s-1,
      respectively. The amplitude of MET current decreased during a constant
      displacement of the hair bundle. This current decay, the adaptation, disappeared
      in the DHSM medium. The disappearance and the emergence of adaptation did not
      have a simple relationship with the block of MET channel by DHSM, but appeared
      with some delay.

PMID- 7504570
TI  - Macrolide antibiotics protect neurons in culture against the N-methyl-D-aspartate
      (NMDA) receptor-mediated toxicity of glutamate.
AB  - The immunosuppressive macrolide FK-506 has been shown to protect neurons in
      culture against glutamate excitotoxicity. This effect was attributed to the
      binding of immunosuppressants to calcineurin-inhibiting immunophilins. We now
      report that also the non-immunosuppressive macrolide antibiotics protect neurons
      in culture against NMDA- but not kainate-mediated excitotoxicity. The effect was
      structure-dependent: larger macrolide rings were more active. Macrolides did not
      affect the 3-(2-carboxypiperazin-4yl)-propyl-1-phosphonic acid (CPP) binding or
      the NMDA-mediated calcium influx.

PMID- 7504571
TI  - Ethical issues in drug selection for schizophrenia.
AB  - The introduction of neuroleptics over 40 years ago was a landmark in medical
      history. Although effective, antipsychotics have many side-effects, some severe.
      Because of the great needs in this therapeutic area, there has been a risk of
      viewing the introduction of new agents such as clozapine as panaceas. The true
      advantages of the new atypical neuroleptics need to be assessed realistically, by
      critically evaluating their effects on positive and negative symptomatology,
      potential adverse effects and cost benefit. Due in part to the toxic effects of
      neuroleptics, obtaining consent to treatment is fraught with complexities of a
      legal and ethical nature. However, despite the many burdensome aspects of this
      disease, including the high risk of suicide among patients, clinicians should
      foster patients insight and a collaborative approach to coping with
      schizophrenia.

PMID- 7504572
TI  - New antipsychotic medications: do research results relate to clinical practice?
AB  - A number of new agents to treat schizophrenia have been, or will soon be,
      introduced that address the limitations of traditional neuroleptics. The new
      class of atypical neuroleptics promises better efficacy and/or side-effects
      profiles, leading to improved overall clinical outcomes. However, in order to
      assess the potential clinical value of these new therapies, it is important not
      only to study the results of various clinical trials, but also to analyze the
      methodology and design of the trials themselves. An understanding of the relevant
      patient-related issues, outcome measures, pharmacological and non-pharmacological
      factors is necessary to apply the findings of clinical trials to daily clinical
      practice.

PMID- 7504573
TI  - Pharmacological profile of risperidone.
AB  - The pharmacodynamics and pharmacokinetics of risperidone, an important atypical
      antipsychotic drug with potent serotonin-5-HT2 and dopamine-D2 receptor blocking
      effects, are presented. The pharmacology of atypical versus typical antipsychotic
      drugs is discussed in the contest of a pathophysiological conceptualization for
      schizophrenia which incorporates a parkinsonian model with an important role for
      serotonin and excitatory amino acid neurotransmission. In the normal therapeutic
      dose range, risperidone displays dose-linear pharmacokinetics in humans and
      reaches steady-state within 24 hours. Risperidone metabolism yields a active
      metabolite, 9-OH-risperidone, that has a similar pharmacological profile to the
      patient compound and therefore contributes to the clinical efficacy of the drug.

PMID- 7504574
TI  - Clinical review of risperidone.
AB  - Phase II clinical trials with risperidone have proven it to have a potent
      antipsychotic effect, improving both positive and negative symptoms of
      schizophrenia. It was found to have a low potential for inducing extrapyramidal
      symptoms and has been shown to have a possible antidyskinetic effect without
      increasing parkinsonism. Risperidone has a rapid onset of action and a favourable
      side-effect profile. One-year data on risperidone suggest that its therapeutic
      action in patients with chronic schizophrenia can be maintained without the
      significant neurological side-effects associated with the use of standard
      neuroleptics.

PMID- 7504575
TI  - Clinical considerations in the use of risperidone.
AB  - Clinical studies to date have shown that risperidone is an effective
      antipsychotic agent in the treatment of both positive and negative
      symptomatologies, with a side-effect profile that is superior to standard
      neuroleptics. It may represent a potentially useful first-line agent in the
      treatment of schizophrenia, and clinicians may consider switching to risperidone
      if current neuroleptic therapy yields poor control of symptoms or problematic
      side-effects, such as extrapyramidal symptoms or tardive dyskinesia. This article
      discusses the relevant clinical considerations in switching neuroleptics and
      proposes practical guidelines on issues such as dosing and course of therapy with
      risperidone.

PMID- 7504576
TI  - Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial.
AB  - BACKGROUND: Electrochemotherapy is a new antitumor treatment consisting of
      electrical pulses administered to the tumor several minutes after intravenous
      injection of bleomycin. In mice, important antitumor effects were observed on
      subcutaneously transplanted tumors and on spontaneously occurring mammary
      carcinomas. Cures were obtained after one single treatment combining bleomycin
      and electric pulses. In humans, permeation nodules seemed an adequate oncologic
      situation to assay this new procedure. The authors report the first Phase I-II
      trial of electrochemotherapy. METHODS: Eight patients with 40 permeation nodules
      of head and neck squamous cell carcinomas were treated with 10 mg/m2 bleomycin
      intravenous bolus, followed by four or eight short (100 microseconds) and intense
      (1300 V/cm) pulses administered through two external electrodes located on each
      side of the treated nodule. RESULTS: An instantaneous painless contraction of the
      underlying muscles was regularly observed. Neither local nor general side effects
      were observed, and electrochemotherapy was well tolerated. In addition, a clear
      local antitumor efficacy was found: 23 (57%) nodules were in clinical complete
      response within a few days. CONCLUSION: The absence of toxicity, the good
      tolerance by the patients, and the net antitumor effects observed are encouraging
      for additional electrochemotherapy developments in clinical oncology.

PMID- 7504578
TI  - Casodex--mechanisms of action and opportunities for usage.

PMID- 7504577
TI  - Prognostic factors in metastatic prostate cancer.
AB  - Androgen deprivation therapy is the initial treatment choice for metastatic
      disease. When enrolling patients into androgen deprivation trials, it is
      important to consider stratification of enrollees based on prognostic factors
      that have been identified as important in determining the likelihood of response.
      Prognostic factors are also helpful in identifying which patients are less likely
      to respond to treatment; this information also would help to counsel patients.
      Performance status is an important prognostic factor; however, its impact is
      minimal because the great majority of men who receive treatment for advanced
      disease have a normal performance status. Hemoglobin, alkaline phosphatase, and a
      semiquantitative grading scale for the number of metastatic foci on the bone scan
      are useful prognostic factors. The pretreatment serum testosterone level is a
      powerful prognostic factor. Patients with a low serum testosterone level have a
      shorter progression-free survival than men whose pretreatment serum testosterone
      level is above normal. The prognostic importance of pretreatment serum
      testosterone level has been evaluated in studies using treatment methods that
      lower this level to castrate levels. Recently, we found that serum testosterone
      level was not a prognostic factor for men taking the nonsteroidal antiandrogen,
      Casodex (Zeneca, Wilmington, DE), which does not alter the serum testosterone
      level. The pretreatment serum prostatic-specific antigen also is a prognostic
      factor. This antigen may be the best single method for monitoring patients in
      regard to response to or progression following therapy. The return of the
      prostatic-specific antigen level to normal (< 4 ng/ml), or the decline in the
      prostatic-specific antigen level of > 90% indicates a prolonged progression-free
      survival. In the future, it will be interesting to incorporate both the initial
      prognostic factors as well as monitor the prostatic-specific antigen into a
      multivariate analysis, which will be highly predictive of a man's response to
      treatment.

PMID- 7504579
TI  - Structural studies of the Vibrio cholerae O:5 O-antigen polysaccharide.
AB  - The O-polysaccharide from Vibrio cholerae O:5 has been investigated, using NMR
      spectroscopy as the main method. Fast atom bombardment mass spectrometry (FABMS)
      studies of fragments obtained on treatment with anhydrous hydrogen fluoride or
      methanolic hydrogen chloride gave further structural information. Some structural
      features were also determined by comparison of nuclear Overhauser enhancement
      (NOE) contacts with calculated H-H distance in different oligosaccharide models.
      It is concluded that the O-polysaccharide has the following structure, in which D
      Qui p NAc4NAc is 2,4-diacetamido-2,4,6-trideoxy-D-glucose, and D-Fuc p 3NX is 3
      amino-3,6-dideoxy-D-galactose acylated with a (R,R)-3-hydroxy-3-methyl-5
      oxoproline group. [formula: see text]

PMID- 7504580
TI  - Structure of the O-specific polysaccharide of the O23 antigen (LPS) from
      Escherichia coli O23:K?:H16.
AB  - The polysaccharide moiety of the O23 antigen (lipopolysaccharide) consists of D
      glucose, D-galactose, 2-acetamido-2-deoxy-D-glucose, and 2-acetamido-2-deoxy-D
      galactose in the molar ratios 2:1:2:1. Methylation analysis of the polysaccharide
      as well as one- and two-dimensional 1H and 13C NMR spectroscopy of the
      polysaccharide and a trisaccharide obtained by Smith degradation showed that the
      O23 polysaccharide has the primary structure [formula: see text].

PMID- 7504581
TI  - Structural comparison of the O4-specific polysaccharides from E. coli O4:K6 and
      E. coli O4:K52.
AB  - Two distinct forms of the O4 antigen (LPS) from E. coli were analysed by 1H and
      13C NMR spectroscopy. Both consisted of D-glucose, L-rhamnose, 2-acetamido-2,6
      dideoxy-L-galactose (L-FucNAc), and 2-acetamido-2-deoxy-D-glucose. Their
      structures were found to be [formula: see text]. In the O4-specific
      polysaccharide from E. coli O4:K3, O4:K6, and O4:K12, X is alpha-D-Glcp. In the
      O4 specific polysaccharide from E. coli O4:K52, the rhamnose residue is not
      substituted (X = H).

PMID- 7504582
TI  - The characterization of the O-antigen of Escherichia coli 064:K99
      lipopolysaccharide.
AB  - The structure of the O-polysaccharide of the smooth lipopolysaccharide (LPS)
      produced by Escherichia coli O64:K99 was investigated by SDS-PAGE, composition,
      periodate oxidation, methylation, partial hydrolysis, and 1D and 2D nuclear
      magnetic resonance analyses, made on the native o-chain and its reduction and
      periodate degradation products. The E. coli O64 antigenic O-chain was found to be
      a high molecular weight glycan composed of D-galactose, D-glucuronic acid, 2
      acetamido-2-deoxy-D-glucose, and 2-acetamido-2-deoxy-D-mannose (2:1:1:1) and was
      a polymer of branched pentasaccharide repeating units having the structure:
      [formula: see text]

PMID- 7504583
TI  - Control of the synthesis of dextran and acceptor-products by Leuconostoc
      mesenteroides B-512FM dextransucrase.
AB  - In the maltose-acceptor reaction of Leuconostoc mesenteroides B-512FM
      dextransucrase, some of the D-glucose moieties of sucrose are diverted from the
      synthesis of dextran and are transferred to the nonreducing end of maltose to
      form panose. Glucose is also transferred to panose and to subsequent acceptor
      products to give a homologous series of isomaltosyl dextrins attached alpha-(1-
      >6) to maltose. Three experimental parameters were studied to obtain quantitative
      information about the yield and distribution of acceptor products and the yield
      of dextran: (a) the ratio of maltose to sucrose, (b) the concentration of maltose
      and sucrose, and (c) the amount of enzyme. The reactions were run with
      [14C]sucrose and the amount of each acceptor product and the amount of dextran
      synthesized were determined for (a), (b), and (c) by TLC separation and
      measurement of the radioactivity with a PhosphorImager. It was found that an
      increase in the ratio of maltose to sucrose increased the amount of acceptor
      products with a concomitant decrease in the synthesis of dextran. Further, as the
      ratio was increased, the number of acceptor-products decreased. When the
      concentrations of maltose and sucrose were increased and the ratio was maintained
      at 1:1, there also was a decrease in the amount of dextran and an increase in the
      amount of acceptor-products. In addition, there was a decrease in the amount of
      dextran and an increase in the amount and number of acceptor-products when the
      amount of enzyme was increased. The first acceptor-product can be exclusively
      obtained without the formation of any dextran, by using a specific ratio and
      concentration of maltose and sucrose and a specified amount of enzyme.

PMID- 7504584
TI  - Growth factors and angiogenesis.
AB  - The list of growth factors with angiogenic potential is growing. It is not clear
      why so many factors with angiogenic potential exist, although Folkman postulated
      that this apparent redundancy is indicative of the essential nature of the
      angiogenic response. Additionally, these factors or their close relatives have
      other biological activities, including developmental morphogenesis,
      tumourigenesis, regeneration of injured tissue, and immunosignalling. Recent
      advances in the understanding of these factors include primary peptide sequence
      for all but one peptide growth factor included in this review, identification of
      cell surface receptors for many, and extensive characterisation of biological
      potential. Despite the torrent of data on angiogenic growth factors in the last
      decade, the chasm between form and physiology remains formidable.

PMID- 7504585
TI  - Expression of basic and acidic fibroblast growth factors and their receptor in
      normal and atherosclerotic human arteries.
AB  - OBJECTIVE: Acidic and basic fibroblast growth factors (FGF) are potent mitogens
      for vascular endothelial and smooth muscle cells and also promote angiogenesis.
      Given that atheroma is associated with the proliferation of a range of cell
      types, including smooth muscle cells, it has been proposed that these growth
      factors may play a part in the genesis and/or maintenance of atheromatous
      lesions. The aim of our study was to examine the distribution of acidic and basic
      FGF and their known receptor, fibroblast growth factor receptor 1 (FGFR-1), in
      normal and atherosclerotic arteries. METHODS: Formalin fixed was embedded
      archival material from a wide range of vessels was examined using a three stage
      avidin-biotin immunoperoxidase technique and specific polyclonal antibodies to
      acidic and basic FGF and FGFR-1. RESULTS: In normal arteries basic FGF
      immunoreactivity was found in medial smooth muscle cells and adventitial blood
      vessels, the luminal endothelium being non-reactive. Acidic FGF expression was
      observed predominantly in adventitial fibroblasts, while FGFR-1 expression was
      confined to the adventitial microvasculature. In early, simple, and advanced
      lesions acidic and basic FGF were expressed in macrophages and smooth muscle
      cells, the principal cell types involved in atherosclerotic lesion formation.
      Increased expression of basic FGF and FGFR-1 was particularly associated with
      neovascularisation of the atheromatous lesions. CONCLUSIONS: Acidic and basic FGF
      are expressed in early, simple and advanced atherosclerotic plaques. This
      suggests that in vivo these growth factors may have a role in the genesis of this
      disease. Basic FGF and FGFR-1 may potentially be involved in plaque
      neovascularisation. Such FGF driven angiogenic events may be central to the life
      threatening complications of atheroma and provide new options for therapeutic
      intervention.

PMID- 7504586
TI  - Generation and localisation of monoclonal antibodies against fibroblast growth
      factors in ischaemic collateralised porcine myocardium.
AB  - OBJECTIVE: The collateral circulation plays a critical role in the prognosis of
      ischaemic heart disease, with a clear correlation between neovascularisation,
      infarction, and tissue recovery. The aim of the study was to address the question
      of whether endogenous acidic and basic fibroblast growth factors (FGF)
      participate in ischaemia induced collateral enlargement and development in the
      myocardium, and also which cells may represent the source of these growth
      factors. METHODS: Eight pigs received an ameroid constrictor around the left
      circumflex coronary artery which, by slow coronary occlusion, induces ischaemia
      and collateral growth in the left ventricle. The degree of stenosis and
      development of collaterals were determined angiographically. About 14 d after
      constrictor implantation pigs were killed and hearts were excised and prepared
      for western blot analysis and immunohistochemistry. Monoclonal antibodies were
      raised against acidic and basic FGF, characterised for their specificity, and
      used for the localisation of growth factors in sections of ischaemic and normal
      pig heart. RESULTS: The eight pigs included in this study showed a gradual 70
      100% left circumflex coronary stenosis about 14 d after implantation of the
      constrictor. Out of four pigs with a complete occlusion, three developed visible
      collaterals. Antibody staining to acidic FGF was detected only in hearts from
      pigs with complete occlusion of the coronary artery. The growth factor was
      localised in cardiomyocytes close to small necrotic tissue patches. In control
      tissue no acidic FGF staining was evident. Basic FGF could not be detected in
      ischaemic or in normal perfused pig hearts. CONCLUSIONS: These data show that (1)
      complete occlusion of the left circumflex coronary artery in pig hearts induces
      collateral growth; (2) cardiomyocytes are able to produce acidic FGF in response
      to ischaemia, thus providing a mitogen for endothelial cells; (3) endogenous
      basic FGF, which was not detected in normal or ischaemic pig hearts, appears not
      to play an important role in ischaemia induced collateral growth at the chosen
      time point of investigation.

PMID- 7504587
TI  - Platelet adhesion to human vascular endothelium is modulated by constitutive and
      cytokine induced nitric oxide.
AB  - OBJECTIVE: The aim was to study whether basal or cytokine stimulated generation
      of nitric oxide (NO) modulates platelet adhesion to human umbilical vein
      endothelial cells (HUVEC). METHODS: The adhesion of 111In labelled human
      platelets to transfected HUVEC (SGHEC-7) was measured either alone or after
      incubation of SGHEC-7 cells for 18 h with interleukin-1 beta (IL-1 beta) and/or
      tumour necrosis factor alpha (TNF alpha). The activity of NO synthase in these
      cells was measured by formation of citrulline. The effects of dexamethasone (0.3
      microM) and NG-monomethyl-L-arginine (L-NMMA, 100 microM) on these two variables
      were determined. RESULTS: Stimulation of SGHEC-7 cells with IL-1 beta or TNF
      alpha (each at 1-30 ng.ml-1) caused them to express the inducible NO synthase, an
      effect that was prevented by dexamethasone. Platelet adhesion to unstimulated
      SGHEC-7 cells was < 0.1% (n = 3) and was increased to 0.7 (SEM 0.2)% by L-NMMA
      but was not affected by dexamethasone. Stimulation of the cells with IL-1 beta
      and TNF alpha increased platelet adhesion to a maximum of 2.2(0.4)%. This
      increase was enhanced by both dexamethasone and L-NMMA. The effect of L-NMMA was
      prevented by L-arginine. CONCLUSIONS: Inhibition of NO synthesis by L-NMMA
      potentiates platelet adhesion to unstimulated SGHEC-7 cells, showing that basally
      released NO regulates platelet adhesion. Stimulation of SGHEC-7 cells by
      cytokines increases their adhesive properties but at the same time causes them to
      express the inducible NO synthase. Nitric oxide generated by this enzyme
      contributes to the modulation of the adhesive properties of the endothelial
      cells. Thus both constitutive and inducible NO synthases modulate endothelial
      cell thrombogenicity.

PMID- 7504588
TI  - Transmeiotic differentiation of male germ cells in culture.
AB  - A cell culture system that supports the differentiation of male germ cells
      through meiosis is described. It takes advantage of the properties of a cell
      line, 15P-1, established from testicular cells of transgenic mice that express
      the large T protein of polyoma virus in the seminiferous epithelium. This line
      exhibits features characteristics of Sertoli cells, including transcription of
      the Wilms' tumor (WT1) and Steel genes. Cells of the 15P-1 type support the
      meiotic and postmeiotic differentiation in cocultures of diploid premeiotic germ
      cells into haploid spermatids expressing the protamine (Prm-1) gene. When
      cocultured with 15P-1 cells, testicular cells explanted from immature 9-day-old
      animals, before the onset of the first meiosis, generated tetrads of haploid
      cells with the morphology of round spermatids and initiated protamine
      transcription.

PMID- 7504589
TI  - RNA editing of apocytochrome b (cob) transcripts in mitochondria from two genera
      of plants.
AB  - Editing of the complete coding region of cob transcripts from two genera of
      plants has been studied by cDNA sequence analysis. Eighteen and nine C residues
      are edited into U in the mitochondrial transcripts from wheat and potato
      respectively. Both systems share eight common editing sites; ten codons edited in
      wheat are "pre-edited" at the genomic level in potato, and one codon edited in
      potato is "pre-edited" in wheat. Most amino-acid modifications lead to
      hydrophobic residues and increase the homology between the COB polypeptides and
      the corresponding protein of other species. In two out of the nine potato cDNA
      clones, an additional C-to-T modification, which also leads to a change in the
      encoded amino acid, was identified. Heterogeneity observed at the carboxy
      terminus of the COB open reading frame in Triticum aestivum and Triticum
      timopheevi is not corrected by editing.

PMID- 7504590
TI  - Smooth muscle cell abundance and fibroblast growth factors in coronary lesions of
      patients with nonfatal unstable angina. A clue to the mechanism of transformation
      from the stable to the unstable clinical state.
AB  - BACKGROUND: The mechanisms responsible for the transformation of stable angina to
      unstable angina, a major cause of morbidity and mortality, are commonly believed
      to be plaque rupture and thrombosis. We determined whether additional mechanisms
      are operative by analyzing the histopathology and immuno-histopathology of
      coronary plaques retrieved by directional atherectomy of patients with unstable
      angina in whom no intraluminal thrombus was demonstrated by angiography. METHODS
      AND RESULTS: The histological findings of atherectomy specimens from 34 patients
      with unstable angina were compared with those of 24 patients with postangioplasty
      restenosis, whose lesions are known to be composed of smooth muscle cells (SMCs),
      and 10 patients with stable angina, whose lesions contain relatively few SMCs. We
      also studied the expression of acidic and basic fibroblast growth factors (aFGF
      and bFGF), whose role in the vascular response to injury has been established.
      Specimens from unstable angina resembled those from postangioplasty restenosis in
      regard to SMC abundance (scale, 0 to 3; 1.4 +/- 0.9 versus 1.7 +/- 0.9; P = NS),
      and both differed from those of stable angina. Thrombus and/or hemorrhage
      occurred in only 34% of patients with unstable angina (compared with 8% of
      restenosis patients and in none of stable angina patients). Active lesions
      (defined as lesions (defined as lesions containing one or more of the following:
      thrombus, hemorrhage, abundant and disorganized SMCs in the presence of loose
      connective tissue, or inflammatory infiltrate) were observed in 56% of the
      unstable angina patients and in 50% of the restenosis patients but in none of the
      stable angina patients. The expression of aFGF and bFGF was detected in 80% to
      100% of unstable angina (n = 11) and restenosis (n = 10) specimens but in only 1
      of 5 stable angina specimens. CONCLUSIONS: Microscopic evidence of thrombosis and
      plaque rupture occurred in only one third of unstable angina patients, selected
      because they had no angiographic evidence of intracoronary thrombus. Moreover,
      their lesions resembled those of restenosis patients in regard to SMC abundance,
      lesion activity, and the expression of aFGF and bFGF. Our findings therefore
      suggest that an alternative mechanism to plaque rupture and thrombus formation
      may be operative in the precipitation of unstable angina; namely, in a subset of
      patients, SMC proliferation may lead to gradual plaque expansion and thereby to
      lumenal narrowing and unstable angina. Our data also suggest a role for aFGF and
      bFGF in this process.

PMID- 7504591
TI  - Postextrasystolic potentiation. Do we really know what it means and how to use
      it?
AB  - Postextrasystolic potentiation (PESP), the increase in contractility that follows
      an extrasystole, is an interesting phenomenon that has been known for almost 100
      years. The literature on this effect is reviewed. It is found that there is
      significant evidence that the phenomenon is independent of muscle loading and
      represents a distinct property of the myocardium. Examination of the literature
      pertaining to the cause of the effect suggests that calcium shifts within the
      sarcoplasmic reticulum are responsible, although there are some conflicts with
      this conclusion. Regarding the utility of PESP as a diagnostic test of latent
      viability of ischemic myocardium, the literature review reveals contradictions
      and conflicts with several methodological problems of the experiments. Finally,
      concerning the utility of continuous PESP (paired-pacing) to augment ventricular
      function in the failing ventricle, the studies again are inconclusive and
      methodologically suspect. Conditions for the proper analysis of the PESP response
      are reported, and suggestions for future studies are introduced.

PMID- 7504592
TI  - Multiple forms of prostate-specific antigen in serum: differences in
      immunorecognition by monoclonal and polyclonal assays.
AB  - Prostate-specific antigen (PSA) in serum is primarily complexed with alpha 1
      antichymotrypsin (alpha 1-ACT). However, 12-15% of prostate cancer (PCa) patients
      present with the predominant form being uncomplexed (free) PSA (Lilja et al.,
      Clin Chem 1991;37:1618-24). We report that commercial immunoassays demonstrate
      variations in reactivity, especially to the uncomplexed form. We fractionated and
      analyzed commercial controls, PSA complexes prepared in vitro, and sera from
      patients with PCa or benign prostatic hyperplasia, using molecular sieve
      chromatography and Hybritech Tandem-R, Abbott IMx, and Ciba Corning ACS PSA
      assays. Peak integration of PCa samples demonstrated ACS:Tandem-R ratios of 1-1.3
      for PSA/alpha 1-ACT complex. In contrast, ratios of uncomplexed peaks ranged from
      2 to 4, suggesting a greater reactivity of the uncomplexed form in the ACS PSA
      assay. Discrepancies between assays, when PSA was measured in unfractionated
      sera, correlated directly with the percentage of the uncomplexed form. In
      controls, fractionation revealed the presence of uncomplexed PSA only, with
      ratios of ACS:Tandem-R and IMx:Tandem-R of 3:1 and 1.8:1, respectively.
      Immunoblots of PCa sera detected uncomplexed PSA (approximately 30 kDa) and PSA
      complexes of approximately 95 kDa (PSA/alpha 1-ACT) and > 200 kDa, indicative of
      alpha 2-macroglobulin. Maximal recognition of all forms of PSA may be important
      for early detection of disease progression.

PMID- 7504593
TI  - Combined serum amylase and lipase determinations for diagnosis of suspected acute
      pancreatitis.
AB  - Serum amylase and lipase measurements are often used to diagnose acute
      pancreatitis. This study addresses the question of whether it is advantageous to
      order serum amylase and lipase tests simultaneously. We evaluated performance of
      the two tests separately and in combination through a retrospective study of
      patients for whom both amylase and lipase determinations were ordered. Initial
      analysis of test performance was conducted with a uniformly applied criterion
      based on determination of optimal sensitivity-specificity pairs. Individual tests
      and combinations of tests, including the "AND" and "OR" rules and discriminant
      functions, were examined. Only the discriminant approach demonstrated better
      performance than the lipase test alone. This finding was subsequently confirmed
      by logistic regression analysis. We conclude that ordering both tests
      simultaneously can be advantageous in diagnosing acute pancreatitis when a
      bivariate approach is used; however, this must be weighed against the
      difficulties associated with clinical implementation of such approaches.

PMID- 7504594
TI  - Improved rapid procedure for simultaneous determinations of hemoglobins A1a, A1b,
      A1c, F, C, and S, with indication for acetylation or carbamylation by cation
      exchange liquid chromatography.
AB  - Although the clinical utility of glycohemoglobin (HbA1c) as an indicator of blood
      glucose control is generally accepted, the use of cation-exchange liquid
      chromatography for its quantification is controversial, given numerous studies
      that show no correlation between HbA1c and other indicators of blood glucose
      control in uremic subjects. We report a specific cation-exchange liquid
      chromatographic method that measures simultaneously HbA1a, HbA1b, HbA1c, HbF,
      HbA0, HbC, and HbS quickly and reproducibly. Carbamylation or acetylation is
      indicated by extra peaks. Carbamylated hemoglobin increased the result for HbA1c
      by as much as 1% above the nonuremic value. The method is a fast (approximately
      15 min per sample), easy to perform, reproducible, and sensitive screening method
      for abnormal hemoglobins. Within-assay CVs were < 0.7% in all cases and between
      assay CVs were < 1.4%.

PMID- 7504595
TI  - Routine acid phosphatase testing for screening and monitoring prostate cancer no
      longer justified.

PMID- 7504596
TI  - Ultraviolet recall associated with etoposide and cyclophosphamide therapy.
AB  - Ultraviolet recall (UR) or sunburn reactivation is an infrequently reported
      phenomenon. It is characterized by an erythematous eruption in the distribution
      of previous ultraviolet-induced sunburn. The timing of the eruption correlates
      well with the speculation that it is induced by the administration of a
      chemotherapeutic agent(s). The case of a young man who developed UR after
      treatment with etoposide (VP16) and cyclophosphamide is reported.

PMID- 7504597
TI  - What is the role of human intestinal intraepithelial lymphocytes?

PMID- 7504599
TI  - Antibodies to proteinase 3 increase adhesion of neutrophils to human endothelial
      cells.
AB  - The detection of anti-neutrophil cytoplasmic antibodies (ANCA), especially those
      with specificity for proteinase 3, is important in the diagnosis and in
      monitoring disease activity of Wegener's granulomatosis and related vasculitides.
      An ubiquitous feature of all ANCA-associated acute vascular injury is lytic
      necrosis. Adhesion of neutrophils to endothelium is a fundamental early step of
      the inflammatory response. Recently we were able to show that ANCA recognize
      their target antigen (proteinase 3) translocated into the membrane of human
      endothelial cells. The aim of this study was to investigate the effect of ANCA on
      the adhesion of neutrophils to human endothelial cells. Incubation of endothelial
      cells with affinity-purified antibodies to proteinase 3 (IgG- and F(ab')2
      fractions) led to a marked increase of neutrophil adhesion, with a peak after 4 h
      and a rapid decrease after 8 h. This effect could be inhibited by preincubation
      of the endothelial cells with an antibody to endothelial-leucocyte adhesion
      molecule-1 (ELAM-1). Incubation with antibodies to proteinase 3 also led to an
      increase of endothelial ELAM-1 expression as measured in a cyto-ELISA and by flow
      cytometry. Our data demonstrate a direct effect of ANCA on neutrophil-endothelial
      interactions. The enhanced adhesion of neutrophils occurs time-dependently via
      induction of ELAM-1 expression on the surface of endothelial cells. Our data give
      a hint of an ANCA-mediated mechanism of endothelial injury via induction of
      neutrophil adhesion to vascular endothelium in Wegener's granulomatosis and other
      ANCA-related vasculitides.

PMID- 7504598
TI  - Cationic and high affinity serum IgG anti-dsDNA antibodies in active lupus
      nephritis.
AB  - To investigate differences between cationic anti-dsDNA antibodies during active
      and inactive nephritis, low- and high-affinity IgG anti-dsDNA antibodies were
      prepared from sera of a lupus patient and compared for their binding affinity,
      spectrotype, and idiotype expression. The ratio of high-affinity to low-affinity
      anti-DNA antibodies and the relative avidity of the high-affinity anti-DNA
      antibodies decreased when active nephritis became inactive. Isoelectric focusing
      showed that cationic anti-dsDNA populations were present predominantly in the
      high-affinity fraction during active nephritis and in the low-affinity fraction
      during inactive nephritis. Idiotypic analysis by ELISA and Western blotting
      showed that the high-affinity cationic anti-DNA antibodies during active
      nephritis were idiotypically different from their low-affinity counterparts
      during inactive nephritis. The differences in binding affinity and idiotypy of
      the cationic anti-dsDNA antibodies suggest that certain serum IgG anti-dsDNA
      antibodies with both cationic charge and high affinity may be associated with
      active nephritis.

PMID- 7504600
TI  - Recognition of Epstein-Barr virus (EBV)-infected cells by T cell colonies from a
      human chimera: restriction by allogeneic determinants.
AB  - The anti-EBV T cell response was studied in a severe combined immunodeficiency
      patient (PS) who received two transplants of fetal liver cells. His peripheral
      blood mononuclear cells (PBMC) were incubated with EBV and cultured during 15
      days. Eleven colonies were derived from the T lymphocytes causing the regression
      of the infected cell foci: nine were constituted with CD3+ CD4+ CD8- lymphocytes
      and two with CD3+ CD4- CD8+ cells. HLA typing of six colonies showed that two of
      them derived from the first transplant and four from the second one. The colonies
      killed the cells of the lymphoblastoid line (LCL) derived from the recipient (PS
      LCL), but failed to kill the LCL matched with the transplants. With only one
      exception, they all lysed also the LCL derived from the mother or from the
      father, but they were ineffective on the EBV-negative lymphoblasts. Two colonies
      recognized determinants which did not appear to be HLA antigens, although they
      were shared by PS and by one of his parents, two (CD4- CD8+) reacted against the
      LCL which shared HLA-A3 or -A33 with PS-LCL, and four (CD4+ CD8-) lysed the LCL
      sharing HLA-A3, -A33 or -DR5 with PS-LCL, among which only one was demonstrated
      to interact directly with host HLA-class I determinants. These data indicate that
      T lymphocytes differentiating in contact with histo-incompatible determinants may
      express the capability to recognize viral antigens and to lyse virus-infected
      cells in the context of allogeneic MHC or non-MHC molecules.

PMID- 7504601
TI  - Identification of human T cell epitopes in the Mycobacterium leprae heat shock
      protein 70-kD antigen.
AB  - In a number of pathogens, heat shock proteins (hsp) stimulate humoral and
      cellular immune responses despite significant sequence identity with host hsp.
      The 70-kD hsp of Mycobacterium leprae, which shares 47% identity with human hsp70
      at the protein level, elicited a T cell response in most Myco. bovis (bacille
      Calmette-Guerin (BCG)) vaccinees as well as leprosy and tuberculosis patients and
      their contacts. In order to locate T cell epitopes, DNA fragments encoding
      portions of the 70-kD hsp were expressed in the vector pGEX-2T and tested for T
      cell reactivity in an in vitro proliferative assay. Cultures of peripheral blood
      mononuclear cells (PBMC) from BCG vaccinees indicated that the C-terminal half of
      the molecule contained multiple T cell epitopes, as the T cells from a majority
      of Myco. leprae hsp70-reactive individuals responded to C-344. Lower proportions
      of patients with paucibacillary leprosy (36%) and tuberculosis patients (16%)
      responded to C-344. The smaller C-142 fragment which includes the terminal 70
      residues unique to Myco. leprae and is the target for the human antibody response
      elicited a cellular response in few patients and no vaccinees. In order to map T
      cell epitopes, two series of synthetic peptides encompassing the region 278-502
      were prepared. Using overlapping 12mer and 20mer peptides, this region of the
      molecule was found to contain several potential T cell epitopes. The longer
      peptides gave a clearer indication of reactive sequences including regions of the
      molecule which were not identified with the 12mer peptides. Fine mapping of
      reactive peptide pools using the 12mer peptides identified two T cell epitopes.
      Although both were located in regions of the molecule shared with Myco.
      tuberculosis, one appeared to be cross-reactive with the equivalent human
      sequence, and thus has the potential to initiate autoimmune responses.

PMID- 7504603
TI  - Outcome of infants born preterm, with special emphasis on extremely low
      birthweight infants.
AB  - The outcome of extremely low birthweight (ELBW) infants has been reviewed from
      published articles and up-to-date data from Japan. The mortality rate of these
      infants declined significantly from over 90% to below 50% after the introduction
      of intensive care in the 1970s, but the incidence of major neurological sequelae
      remained steady at around 20%. Similarly, the incidence of major neurological
      sequelae did not increase along with the decrement of birthweight, although the
      mortality rate increased significantly. Long-term follow-up of ELBW children
      until school age has revealed poor school performance in spite of the absence of
      major neurological sequelae and the attainment of average intelligence quotient
      scores. Physical growth is retarded initially but generally catches up by the age
      of 8-9 years. In Japan, the neonatal mortality rate of ELBW infants declined from
      56% in 1981 to 25% in 1989 with an increased birth rate of ELBW infants. In ELBW
      infants cared for at Tokyo Women's Medical College during 1984-90, the survival
      rate was 112 out of 134 (84%) and the incidence of major neurological sequelae
      was 15 out of 87 (17%) at 1-8 years old. The viability limit of ELBW infants has
      been discussed based on recent data. As a result of the rapid progress of medical
      care of ELBW infants, their viability limit as defined in the Eugenic Protection
      Law in Japan was amended from 24 completed weeks of gestation to 22 completed
      weeks in 1991.

PMID- 7504602
TI  - Circulating adhesion molecules in tuberculosis.
AB  - Leucocyte-endothelial adhesion molecules have been implicated in the pathogenesis
      of inflammatory diseases. To evaluate their role as markers of disease activity
      in tuberculosis, we have used an antigen capture ELISA to measure the serum
      concentrations of circulating intercellular adhesion molecule-1 (cICAM-1), E
      selectin (cE-selectin) and vascular cell adhesion molecule-1 (cVCAM-1) in 34
      patients with active tuberculosis (27 with pulmonary disease and seven with lymph
      node disease) before the commencement of standard chemotherapy, 15 subjects who
      had previously completed treatment for pulmonary tuberculosis, and 27 healthy
      volunteers. Circulating ICAM-1 and E-selectin levels were significantly elevated
      in patients with active tuberculosis when compared to those with treated disease
      (P < or = 0.01), and healthy controls (P < 0.02). Circulating VCAM-1 was raised
      in patients with active or old pulmonary tuberculosis (P < 0.02 versus healthy
      controls) but not in those with tuberculous lymphadenitis. Significant
      correlations were observed between the levels of cICAM-1 and cE-selectin (p =
      0.63, P = 0.0001), and between cICAM-1 and cVCAM-1 (p = 0.28, P = 0.016). Taking
      the mean +2 s.d. of the serum level in healthy controls as the upper limit of
      normal range, circulating ICAM-1 had the best discriminative power in identifying
      active tuberculosis, being elevated in about 80% of patients but was raised in
      only 6.7% of subjects with treated disease and in 3.7% of normal subjects. Our
      data support the possibility that three adhesion molecules may be involved in the
      pathogenesis of tuberculosis and cICAM-1 may be a useful marker of disease
      activity.

PMID- 7504604
TI  - Long-term outcome of infants born preterm.
AB  - This chapter outlines some of the many long-term health problems to be expected
      in surviving preterm children. They have higher rates of sensorineural
      impairments (such as cerebral palsy, and visual, auditory and intellectual
      impairments) and sensorineural disabilities from these impairments, than children
      born at term. In addition, they grow poorly and have higher rates of other health
      problems, including poorer respiratory health in early childhood. There is little
      doubt that preterm children contribute disproportionately to the prevalence of
      health problems in childhood. However, there are still many gaps in our knowledge
      of the outcome for preterm survivors, particularly regarding outcome in
      adulthood. Obstetricians and neonatologists working in intensive care, as well as
      parents, want to know the long-term outcome for preterm children born today, not
      that of children born a generation ago when fewer preterm children (particularly
      those of extremely low birthweight) survived. Despite the many problems, the
      conclusion is that most preterm children are as healthy as term children,
      suffering only usual childhood illnesses; we feel confident that the majority
      make, and will continue to make, useful contributions to their families and the
      societies in which they live.

PMID- 7504605
TI  - Whole-cell outward currents in freshly dissociated rat placental cells.
AB  - 1. We applied whole cell voltage clamp techniques to freshly dissociated rat
      placental cells (20-21 days gestation). Tetraethylammonium (TEA)-sensitive
      outward currents were recorded in about 50% of cells. 2. The outward current had
      a reversal potential of -50 mV which is more positive than the potassium
      equilibrium potential (-82 mV). 3. The bath solution without NaCl decreased the
      outward current amplitude, while the elimination of only Na ions from the bath
      solution did not modify the outward current. 4. The results suggest a possible
      contribution of chloride ions to the outward currents in rat placental cells.

PMID- 7504606
TI  - Ontogeny of growth hormone (GH), insulin-like growth factors (IGF-I and IGF-II)
      and IGF binding protein-2 (IGFBP-2) in genetically lean and obese swine.
AB  - Serum GH, IGF-I, IGF-II and IGFBP-2 concentrations were determined by
      radioimmunoassay in swine of genetic lines which were selected for high (obese)
      and low (lean) backfat. Blood samples were collected at birth, before and after
      nursing, at 1 and 3 days of age and at weekly or fortnightly intervals until 30
      weeks of age. Overall, GH, IGF-I, IGF-II and IGFBP-2 were highest at birth and
      declined during the first week of postnatal life. An age-by-line interaction was
      apparent for GH and IGF-I during the early neonatal period with levels being
      higher in the lean line than the obese line at 1 day of age and similar at 1 week
      of age. At 3 to 5 weeks of age there was an elevation in GH which was greater in
      lean than obese pigs. IGFBP-2 concentration patterns were characterized by a
      nadir at 5 to 7 weeks of age and a decline from an apex at 8 weeks of age in both
      lines. IGF-II declined steadily from birth until about 10 weeks of age. A
      subsequent increase in IGF-II was then observed between 12 and 22 weeks, which
      was greater in the obese line and in male pigs but not apparent in lean females.
      At birth, pigs which had not nursed had higher GH and IGFBP-2 and lower IGF-I and
      IGF-II concentrations. The effect of nursing on IGF-I was significantly
      influenced by line.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504607
TI  - Palliation of central airway stenoses with the Dumon silicone stent.

PMID- 7504608
TI  - Silicone stents in the management of inoperable tracheobronchial stenoses.
      Indications and limitations.
AB  - BACKGROUND: Various stent models have been developed for the treatment of
      inoperable stenoses of the central airways caused by external compression.
      Increasing use is made of the silicone stents designed by Dumon. We tested their
      technical feasibility, tolerance, and long-term efficacy in relieving respiratory
      symptoms in patients referred for endoscopic palliation of malignant disease.
      METHODS: All procedures were performed under general anesthesia with the use of
      the rigid bronchoscope. We inserted 38 stents in 31 patients (median age, 67
      years; 25 men and 6 women) whose airways showed residual obstruction of > 50
      percent of the lumen after laser resection of endobronchial tumor and/or
      mechanical dilatation of extrinsic compressions. RESULTS: Stent placement and
      removal--where necessary--were easy in all patients, but five stents inserted in
      three patients with short (< or = 2.5 cm) and conical stenoses migrated,
      necessitating emergency removal. In 27 of the remaining 28 patients, stent
      tolerance was excellent; 1 proximal tracheal stent (< 1 cm below the vocal cords)
      had to be removed because of otalgia and dysphagia. One lethal hemoptysis
      occurred within hours after a repeated laser therapy and removal of an indwelling
      stent. No other serious complications occurred. Immediate and lasting relief of
      dyspnea and improvement in performance status (Karnofsky scale, activity index)
      was achieved in 90 percent (28/31) of patients (p < 0.01). The influence of
      adjuvant radiotherapy on local tumor recurrence and survival was analyzed in a
      subgroup of ten patients with stage IIIB squamous cell carcinoma with comparable
      performance status. Five did not undergo adjuvant radiotherapy (group A) and five
      did (group B). In group A, four of five stents were occluded by tumor recurrence
      above or below the stent after a median follow-up of 2 months; in group B, zero
      of five were occluded (p < 0.05) after 4 months. Median survival was 4 months in
      group A and 6 months in group B; the difference did not reach significance.
      CONCLUSIONS: The silicone stents designed by Dumon are easily inserted and
      removed; they are also well tolerated and very efficacious in relieving
      respiratory symptoms caused by extrinsic airway compression. Short and conical
      stenoses present limitations for their use due to increased risk of migration.
      Combined treatment with laser resection, stent insertion, and subsequent
      radiotherapy is necessary to prevent local tumor recurrence and may improve
      survival.

PMID- 7504610
TI  - Preventive effects of sodium molybdate in lead intoxication in rats.
AB  - The role of sodium molybdate (1 mg/kg, intraperitoneally, once daily)
      supplementation during the course of lead exposure (0.1% lead acetate in drinking
      water for 4 weeks) in preventing the accumulation of lead in blood and soft
      tissues and in restoring altered lead-sensitive biochemical variables and the
      levels of hepatic glutathione, lipid peroxidation, blood Na, blood K, and serum
      ceruloplasmin was investigated in rats. The data indicate that sodium molybdate
      significantly protected the uptake of lead in blood, liver, and kidneys and
      restored the lead-induced inhibited activity of blood delta-aminolevulinic acid
      dehydratase, elevation of blood zinc protoporphyrin, hepatic lipid peroxidation,
      and serum ceruloplasmin. The results suggest a significant role of sodium
      molybdate in preventing plumbism.

PMID- 7504609
TI  - Effect of hypolipidemic drugs gemfibrozil, ciprofibrate, and clofibric acid on
      peroxisomal beta-oxidation in primary cultures of rainbow trout hepatocytes.
AB  - Primary cultures of hepatocytes were established from sexually mature male
      rainbow trout (Oncorhyncus mykiss) and treated with the hypolipidemic drugs
      gemfibrozil (0.25-1.25 mM), clofibric acid (2.25-3.00 mM), or ciprofibrate (0.25
      1.00 mM). Significant dose-related increases in peroxisomal fatty acyl-CoA
      oxidase (FACO) were seen after exposure for 48 hr to clofibric acid (P < 0.01)
      and ciprofibrate (P < 0.05) but not gemfibrozil (P = 0.08). Strong correlation
      was obtained between increased acyl-CoA oxidase activity and the relative amount
      of peroxisomal bifunctional enzyme (PBE), further supporting evidence of a
      proliferative effect. These preliminary studies demonstrate that peroxisomal beta
      oxidation can be induced in vitro in a primary rainbow trout hepatocyte system.

PMID- 7504611
TI  - Effects of the pyrethroid insecticide Cypermethrin on the locomotor activity of
      the wolf spider Pardosa amentata: quantitative analysis employing computer
      automated video tracking.
AB  - Wildlife in areas surrounding arable land is almost inevitably exposed to
      pesticide spray. Even at doses far below the lethal level, this presents a threat
      to vulnerable species. The widely used pyrethroid insecticides, including
      Cypermethrin, are known for their direct effect on the locomotor apparatus of
      animals, inducing varying degrees of paresis. Quantitative measurements of the
      voluntary locomotion of animals express an integrated response to changes in
      biochemical and physiological processes. In the present study, the effect of
      Cypermethrin on the voluntary locomotion of the wolf spider Pardosa amentata was
      quantified in an open field setup, using computer-automated video tracking. Each
      spider was recorded for 24 hr prior to pesticide exposure. After topical
      application of 4.6 ng of Cypermethrin, the animal was recorded for a further 48
      hr. Finally, after 9 days of recovery, the spider was tracked for 24 hr.
      Initially, Cypermethrin induced an almost instant paralysis of the hind legs and
      a lack of coordination in movement seen in the jagged and circular track
      appearance. This phase culminated in total quiescence, lasting approximately 12
      hr in males and 24-48 hr in females. Following paresis, the effects of
      Cypermethrin were evident in reduced path length, average velocity, and maximum
      velocity and an increase in the time spent in quiescence. Also, the pyrethroid
      disrupted the consistent distributions of walking velocity and periods of
      quiescence seen prior to pesticide application. Our results suggest that normal
      locomotion had returned 9 days after Cypermethrin application, but that recovery
      of high velocities was still incomplete.

PMID- 7504612
TI  - Uptake and depuration of PCB 77, PCB 169, and hexachlorobenzene by zebra mussels
      (Dreissena polymorpha).
AB  - Zebra mussels (Dreissena polymorpha) were examined for their ability to take up
      and depurate hexachlorobenzene (HCB), 3,3',4,4'-tetrachlorobiphenyl (PCB 77), and
      3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) in the laboratory. The intent was to
      investigate response to acute exposure at high contaminant levels and to observe
      the time course of depuration. Tissue loads of all three compounds taken up from
      food increased rapidly and peaked after 10 (PCB 169), 14 (PCB 77), and 21 (HCB)
      days followed by rapid depuration to equilibrium levels. Peak tissue loads were
      3.7, 3.4, and 3.6 micrograms/g for PCB 169, PCB 77, and HCB, respectively (wet
      weight basis). Equilibrium levels were approximately 1.0 microgram/g for both PCB
      169 and HCB. Uptake rate of PCB 77 followed the order: sediment > food > water.
      Dreissena sampled from five Great Lakes field sites had tissue Aroclor loads
      ranging from 120 to 530 ng/g for Aroclor 1242 and 33 to 270 ng/g for Aroclor 1254
      (wet weight basis). PCB 77 was detected at 1.9 ng/g at one site. Tissue levels
      for both Aroclors in Dreissena were approximately 10 times those of Lampsilis
      siliquoidea, a unionid bivalve to which they were attached. Where Dreissena
      reaches high densities, it is likely to play a significant role in contaminant
      dynamics.

PMID- 7504613
TI  - Comparison of alternative models for predicting the uptake of chlorinated
      hydrocarbons by oligochaetes.
AB  - The uptake of chlorinated hydrocarbons from contaminated sediments by
      oligochaetes was analyzed using three alternative models. Uptake appears to be
      best explained using a model that explicates the relationship of oligochaete body
      burden as a function of weight-dependent feeding rates, fractional absorption,
      and exposure times. The model explains observed variations in body burdens with
      oligochaete weights. Oligochaetes appear to absorb small fractions of ingested
      hydrocarbons. Fractional absorption of ingested contaminants appears to have a
      parabolic relationship with octanol-water partition coefficients and may decrease
      over time.

PMID- 7504615
TI  - Physiology of carbon assimilation in a green alga during exposure to and recovery
      from cadmium.
AB  - The flow of recently photoassimilated carbon into proteins, lipids, and
      polysaccharides was studied with asynchronous Selenastrum capricornutum
      populations during exposure to and recovery from 30 and 100 micrograms Cd.liter
      1. During a 48-hr exposure to Cd, increases in Cd cell quotas were accompanied by
      nearly exponential decreases in growth and photosynthesis and by a disruption of
      the pattern of carbon allocation to macromolecules. In particular, relative to
      the control, the cells exposed to Cd allocated a higher percentage of carbon to
      the synthesis of polysaccharides. After the addition of EDTA (recovery period),
      Cd cell quotas decreased and growth recovery was accompanied by the recovery of
      photosynthesis and by an enhanced flow of carbon to lipids and proteins. The
      results of the experiment suggest that the measurement of the distribution of
      recently photoassimilated carbon into macromolecules has potential for monitoring
      the effects of toxic effluent discharges on primary producers.

PMID- 7504614
TI  - Teratogenic effects of selenium in natural populations of freshwater fish.
AB  - The prevalence of abnormalities and associated tissue selenium residues were
      assessed for the fish population of Belews Lake, North Carolina, and two
      reference lakes in 1975, 1978, 1982, and 1992. Teratogenic defects identified
      included lordosis, kyphosis, scoliosis, and head, mouth, and fin deformities.
      Many fish exhibited multiple malformations and some were grossly deformed and
      distorted in appearance. Other abnormalities observed were edema, exophthalmus,
      and cataracts. Whole-body tissue residues of selenium in the fishes of Belews
      Lake were up to 130 times those in the reference lakes and the incidence of
      abnormalities was some 7 to 70 times greater. Teratogenic defects increased as
      selenium levels rose between 1975 and 1982 and fell with declining selenium
      levels between 1982 and 1992 as selenium inputs into Belews Lake were curtailed.
      The relationship between selenium residues and prevalence of malformations
      approximated an exponential function (R2 = 0.881, P < 0.01; cubic model) for
      centrarchids over the range of 1-80 micrograms/g dry wt selenium and 0-70%
      deformities. This relationship could be useful in evaluating the role of
      teratogenic effects in warm-water fish populations suspected of having selenium
      related reproductive failure. Unique conditions may have existed in Belews Lake
      which led to the high frequency and persistence of deformities in juvenile and
      adult fish. In other, less-contaminated locations competition and predation may
      eliminate malformed individuals in all but the larval life stage. Teratogenesis
      could be an important, but easily overlooked phenomenon contributing to fishery
      reproductive failure in selenium-contaminated aquatic habitats.

PMID- 7504617
TI  - Putrescine (1,4-diaminobutane) as an indicator of pollution-induced stress in
      higher plants: barley and rape stressed with Cr(III) or Cr(VI).
AB  - The performance of the free polyamines as plant stress indicators is studied in
      barley and rape plants grown in nutrient culture, by exposure to Cr(VI) or
      Cr(III) in concentrations ranging from 0 to 100 ppm. Putrescine levels are
      elevated up to 10 times in the leaves of stressed plants compared to those of
      control plants, but neither spermidine nor spermine show any consistent reactions
      on the stress. Cr(VI) is more toxic than Cr(III) and induces putrescine
      accumulation quicker than Cr(III). Chromium concentrations in leaves reach 3000
      5000 ppm (dry wt) after exposure to 100 ppm Cr(VI) and 300-400 ppm (dry wt)
      following exposure to 100 ppm Cr(III). Simultaneously with, or following shortly
      after the putrescine induction, reductions in root growth, chlorosis, induction
      of leaf chitinase activity, and, later, reduced shoot growth and lowered water
      content in leaves are observed. The pattern of the effects indicates that the
      basal toxicity mechanism of the two chromium species is connected to disturbance
      of the normal function of the root. Putrescine induction is an integrated part of
      the response mechanism of the stressed plants, appearing as an early sign of
      stress. However, the chromium concentration of the leaves as a warning of
      chromium-induced stress is judged to be an even more sensitive indicator.

PMID- 7504618
TI  - Influence of dietary calcium on chlordecone-induced biochemical changes in serum
      of rat.
AB  - Male, Sprague-Dawley rats were treated with different (1, 10, 50, and 100 ppm)
      concentrations of chlordecone (Cd) in calcium-sufficient (Ca-S) or calcium
      deficient (Ca-D) diet for 15 days. No significant changes in serum total proteins
      were observed. However, serum nonprotein nitrogen compounds (urea, uric acid, and
      creatinine) and glutamic oxaloacetic transaminase, glutamic pyruvic transaminase,
      creatine kinase, and alkaline phosphatase were significantly increased at 50 and
      100 ppm of Cd. Chlordecone induced more increase in these serum components of
      rats fed with Ca-D as compared to Ca-S diet. Increased serum nonprotein nitrogen
      compounds and enzymes indicate Cd-altered glomerular and hepatic functions.

PMID- 7504616
TI  - Influence of cadmium on life-history characteristics of Folsomia candida (Willem)
      in an artificial soil substrate.
AB  - To understand the consequences of soil pollution on higher levels of biological
      organization, the chain of effects of cadmium on several interrelated responses
      was studied in a chronic toxicity experiment using the collembolan species
      Folsomia candida (Willem) in an artificial soil. The individual parameters
      survival, growth, and number of offspring were determined after different time
      intervals up to 9 weeks. The accumulation of cadmium in springtails and the
      population increase during the experimental period were also determined. By
      combining all the mentioned parameters and their development in time, a detailed
      picture of the action of cadmium on F. candida was obtained. In order of
      decreasing sensitivity the EC50 values for Von Bertalanffy growth, number of
      offspring, population increase, and survival were 256, > 326, 475, and 850
      micrograms Cd/g dry soil, respectively. The ultimate LC50 value and also the
      equilibrium body burden were reached after about 20 days. Reproduction started
      later because of retarded growth, but was not affected directly and eventually
      reached the control level. The results are discussed in light of the seemingly
      contradictory ideas of Halbach (1984, Hydrobiologia 109, 79-96) and Meyer et al.
      (1987, Environ. Toxicol. Chem. 6, 115-126) about the sensitivity of individual
      and population parameters. It appears to be very important to know how individual
      parameters develop in time so that the most sensitive parameter and the
      consequences for higher levels of biological organization can be determined.

PMID- 7504619
TI  - Hydrophilic surface maps of channel-forming peptides: analysis of amphipathic
      helices.
AB  - Ion channels may be formed by bundles of amphipathic alpha-helices aligned
      parallel to one another and spanning a lipid bilayer membrane, with the
      hydrophilic faces of the helices lining a central pore. In order to provide
      insight into the packing of such helices in bundles, a method has been developed
      to evaluate hydrophilic surface maps of amphipathic alpha-helices and to display
      these surfaces in a readily interpretable form. The procedure is based upon
      empirical energy calculations of interactions of a water molecule with an
      amphipathic alpha-helix. The method has been applied to three channel-forming
      peptides: Staphylococcal delta-toxin; alamethicin; and a synthetic leucine- and
      serine-containing peptide. Particular emphasis is placed upon the effects of
      sidechain conformational flexibility on hydrophilic surface maps. A family of
      models of the delta-toxin helix is generated by a simulated annealing procedure.
      The results of hydrophilic surface map analyses provide more exact definition of
      the centre of the hydrophilic face of amphipathic helices, and of the variation
      of the position of the centre in response to changes in sidechain conformation.
      This information is used to define families of preliminary models for a given ion
      channel, as is illustrated for delta-toxin.

PMID- 7504621
TI  - Electrostatic interactions in gramicidin channels. Three-dielectric model.
AB  - A model based on the solution of the electrostatic potential for a geometry of
      three dielectric regions associated with a gramicidin A channel (GA) is
      presented. The model includes a cylindrical dielectric layer to represent the
      peptide backbone and dipole rings to account for dipolar side chains. Image
      potential and dipolar contributions for different orientations and positions
      along the channel are analyzed. The conductance of GA and two analogues obtained
      by substituting the amino acid at position 1 are studied. The numerical
      simulation reproduces experimental results (Barrett et al. 1986, Biophys J 49,
      673-686) and supports the idea that electrostatic dipole-ion interactions are of
      primary importance in gramicidin channel function.

PMID- 7504620
TI  - The double pi pi 5.6 helix of gramicidin A predominates in unsaturated lipid
      membranes.
AB  - The structure of the channel-forming polypeptide gramicidin A (GA) incorporated
      into phosphatidyl-choline (PC) liposomes has been studied as a function of the
      degree of unsaturation of the acyl chains of PC. The initial conformational state
      of GA in reconstituted bilayers is determined by the solvent in which the peptide
      and the lipid are initially co-dissolved, whereas the equilibrium conformational
      state (after heat incubation) is affected by the lipid structure rather than by
      the nature of the solvent. The conformational equilibrium of GA has been studied
      in liposomes prepared from PC having a variable number of double bonds in the
      fatty acid moiety, by circular dichroism and Fourier transform infrared.
      Liposomes were prepared from trifluoroethanol or ethanol solutions and incubated
      at 68 degrees C. GA was shown to retain the conformation of the right-handed pi-
      >6.3 pi<--6.3 helix in PC with saturated acyl chains and with one double bond,
      whereas in dilinoleoyl-PC, having two double bond in each chain, the
      thermodynamically preferred structures are left-handed antiparallel and parallel
      double pi pi 5.6 helices. Natural soybean PC also favours left-handed pi pi 5.6
      helical structures of GA (approximately 75%). This finding is discussed in terms
      of the role of PC unsaturation in the dynamic properties of the lipid matrix.
      Differences between observed FTIR spectra of the increases decreases pi pi 5.6
      helix in solution (and to a larger extent in the membrane) and the calculated IR
      spectra can be interpreted as resulting from deviation of the real structure from
      the theoretically derived ideal helix. The data obtained provide grounds for
      better understanding of a GA channel functioning in lipids of variable degrees of
      unsaturation.

PMID- 7504622
TI  - Role of granulocyte-macrophage colony-stimulating factor in pulmonary fibrosis
      induced in mice by bleomycin.
AB  - The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in
      pulmonary fibrosis elicited in mice by the intratracheal instillation of
      bleomycin was investigated by (1) evaluation of GM-CSF mRNA levels, (2)
      administration of GM-CSF, and (3) administration of anti-GM-CSF antibody. A
      significant increase of the GM-CSF mRNA level was evident in the lung RNA on day
      5 after bleomycin instillation, but not on day 15. Abdominal infusion of GM-CSF
      (0.5 micrograms/h during days 7-15) did prevent the collagen deposition induced
      by bleomycin, as measured by the lung hydroxyproline content on day 15. In
      contrast, anti-GM-CSF antibody markedly aggravated the collagen deposition. On
      histological sections the proportion of lungs showing fibrosing alveolitis was
      decreased by GM-CSF and increased by anti-GM-CSF IgG. The percentage and number
      of macrophages within the bronchoalveolar lavage (BAL) fluid was increased by GM
      CSF infusion and decreased by anti-GM-CSF antibodies. This study demonstrates
      that pulmonary GM-CSF has an inhibitory influence upon the alveolar remodeling
      and collagen deposition associated with pulmonary fibrosis.

PMID- 7504623
TI  - Properties of bacteriorhodopsin derivatives constructed by insertion of an
      exogenous epitope into extra-membrane loops.
AB  - Bacteriorhodopsin (BR) is folded into a bundle of seven alpha-helices which is
      embedded in the cellular membrane of Halobacterium salinarium; these helices are
      connected by short extra-membrane loops, three on the cytoplasmic side and three
      on the outside. Oligonucleotide-directed insertion or replacement mutagenesis was
      used to integrate the C-terminal sequence (13 amino acids long) of Sendai virus L
      protein individually into each of the six helix-connecting loops. The altered
      gene products were obtained by expression of the mutant genes in either
      Escherichia coli or Schizosaccharomyces pombe and were used to reconstitute BR in
      proteoliposomes. In four cases (altered loops B/C, C/D, D/E or E/F), the mutant
      BRs were found to be fully functional as judged by light-driven proton pumping
      and photocycle kinetics. Within the four functional BR variants, recognition of
      the viral epitope by a monoclonal antibody is restricted to modified loops B/C
      and E/F. Immunogold staining of S.pombe cells producing either of the two latter
      BR variants shows that the protein is distributed among various cellular
      membranes but is not present in mitochondrial membranes. Sequence alteration of
      loop A/B or F/G resulted in loss of function, most plausibly due to a folding
      defect of the respective proteins. These results on the one hand document
      differences in structural importance of the various BR extra-membrane loops and
      on the other hand open the door to the construction of multifunctional membrane
      proteins via loop replacement mutagenesis of BR.

PMID- 7504624
TI  - Two distinct mechanisms for negative regulation of the Wee1 protein kinase.
AB  - The Wee1 protein kinase negatively regulates the entry into mitosis by catalyzing
      the inhibitory tyrosine phosphorylation of the Cdc2 protein. To examine the
      potential mechanisms for Wee1 regulation during the cell cycle, we have
      introduced a recombinant form of the fission yeast Wee1 protein kinase into
      Xenopus egg extracts. We find that the Wee1 protein undergoes dramatic changes in
      its phosphorylation state and kinase activity during the cell cycle. The Wee1
      protein oscillates between an underphosphorylated 107 kDa form during interphase
      and a hyperphosphorylated 170 kDa version at mitosis. The mitosis-specific
      hyperphosphorylation of the Wee1 protein results in a substantial reduction in
      its activity as a Cdc2-specific tyrosine kinase. This phosphorylation occurs in
      the N-terminal region of the protein that lies outside the C-terminal catalytic
      domain, which was recently shown to be a substrate for the fission yeast Nim1
      protein kinase. These experiments demonstrate the existence of a Wee1 regulatory
      system, consisting of both a Wee1-inhibitory kinase and a Wee1-stimulatory
      phosphatase, which controls the phosphorylation of the N-terminal region of the
      Wee1 protein. Moreover, these findings indicate that there are apparently two
      potential mechanisms for negative regulation of the Wee1 protein, one involving
      phosphorylation of its C-terminal domain by the Nim1 protein and the other
      involving phosphorylation of its N-terminal region by a different kinase.

PMID- 7504625
TI  - Novel RNA polymerization reaction catalyzed by a group I ribozyme.
AB  - We have converted a bacterial tRNA precursor containing a 205 nt self-splicing
      group I intron into a RNA enzyme that catalyzes polymerization of an external RNA
      substrate. The reaction involves transesterification steps analogous to both the
      forward and reverse exon ligation steps of group I splicing; as such it depends
      entirely on 3' splice site reactions. The RNA substrate is a 20 nt analogue of
      the ligated exons (E1.E2), whose 3' end resembles the 3' terminus of the intron
      RNA enzyme (IVS). The splice junction of the substrate is attacked by the 3' end
      of the intron, then the molecule displaces the original 3' terminal guanosine so
      that the new 3' terminus is brought into the active site and used as the
      attacking nucleophile in the next reaction. Polymerization occurs via a series of
      covalent enzyme-linked intermediates of the structure IVS.(E2)n, where n = 1 to >
      or = 18. The 5' exon accumulates during the course of the reaction and can attack
      the covalent intermediates to produce elongation products of structure E1.(E2)n,
      regenerating the intron RNA enzyme in unchanged form. In this manner, the enzyme
      converts 20 nt oligoribonucleotides into polyribonucleotides up to at least 180
      nt by 10 nt increments. These results have significant implications for the
      evolution of RNA-based self-replicating systems.

PMID- 7504626
TI  - Biosynthesis of nitric oxide activates iron regulatory factor in macrophages.
AB  - Biosynthesis of nitric oxide (NO) from L-arginine modulates activity of iron
      dependent enzymes, including mitochondrial acontiase, an [Fe-S] protein. We
      examined the effect of NO on the activity of iron regulatory factor (IRF), a
      cytoplasmic protein which modulates both ferritin mRNA translation and
      transferrin receptor mRNA stability by binding to specific mRNA sequences called
      iron responsive elements (IREs). Murine macrophages were activated with
      interferon-gamma and lipopolysaccharide to induce NO synthase activity and
      cultured in the presence or absence of NG-substituted analogues of L-arginine
      which served as selective inhibitors of NO synthesis. Measurement of the nitrite
      concentration in the culture medium was taken as an index of NO production.
      Mitochondria-free cytosols were then prepared and aconitase activity as well as
      IRE binding activity and induction of IRE binding activity were correlated and
      depended on NO synthesis after IFN-gamma and/or LPS stimulation. Authentic NO gas
      as well as the NO-generating compound 3-morpholinosydnonimine (SIN-1) also
      conversely modulated aconitase and IRE binding activities of purified recombinant
      IRF. These results provide evidence that endogenously produced NO may modulate
      the post-transcriptional regulation of genes involved in iron homeostasis and
      support the hypothesis that the [Fe-S] cluster of IRF mediates iron-dependent
      regulation.

PMID- 7504629
TI  - Levodropropizine reduces capsaicin- and substance P-induced plasma extravasation
      in the rat trachea.
AB  - We investigated the effect of the non-opioid, peripherally acting antitussive
      agent levodropropizine to reduce neurogenic plasma extravasation in the rat
      trachea. Levodropropizine (10, 50 and 200 mg/kg) reduced in a dose-dependent
      manner the extravasation of Evans blue dye evoked by capsaicin. Levodropropizine
      inhibited also substance P-evoked extravasation, whereas it did not affect the
      extravasation evoked by platelet activating factor. Levodropropizine (10 and 100
      microM) did not affect the contraction produced by [Sar9,Met(O2)11]substance P, a
      selective agonist for tachykinin NK1 receptors, in the rat urinary bladder in
      vitro. These data indicate that levodropropizine inhibits capsaicin-induced
      plasma extravasation: (a) acting at a postjunctional level; (b) exhibiting
      neuropeptide selectivity and; (c) via a mechanism independent of tachykinin NK1
      receptor blockade. Irrespective of the mechanism, this novel antiinflammatory
      action of levodropropizine underlines its potential role in inflammatory airway
      diseases such as bronchial asthma.

PMID- 7504630
TI  - PCA 50941, a novel Ca2+ channel agonist.
AB  - PCA 50941 is a novel 1,4-dihydropyridine derivative. Its vasoconstricting effects
      prompted a systematic comparison with the prototypic Ca2+ channel activator, Bay
      K 8644. The two compounds exhibit marked analogies and differences in their
      cardiovascular profiles. PCA 50941 exhibits a pronounced vascular over cardiac
      selectivity while Bay K 8644 has both potent vasoconstrictor effects and strong
      cardiac positive inotropic actions. PCA 50941 exhibits either poor positive
      inotropic effects (isolated guinea-pig atria) or clear negative inotropic effects
      (isolated perfused rat heart). Both compounds reduced by 10-40% the coronary flow
      in the perfused rat heart. However, PCA 50941 had slight vasoconstrictor effects
      in pig coronary arteries, causing their relaxation at nanomolar/micromolar
      concentrations; this contrasts with the almost pure, marked vasoconstrictor
      effects of Bay K 8644 in coronary arteries. In the rat aorta PCA 50941 exhibited
      a biphasic pattern of vasoconstriction and vasorelaxation, and in portal vein it
      markedly reduced the Ca(2+)-evoked contractions; Bay K 8644 behaved as a pure
      vasoconstrictor in these two preparations. It is concluded that the racemic
      compound, PCA 50941, exhibits different degrees of Ca2+ agonism and Ca2+
      antagonism by acting upon 1,4-dihydropyridine receptors of different
      cardiovascular tissues. Its tissue selectivity and its prolonged duration of
      action give PCA 50941 a cardiovascular profile more favourable than that of other
      1,4-dihydropyridine Ca2+ agonist existing to date.

PMID- 7504627
TI  - Translational regulation via iron-responsive elements by the nitric oxide/NO
      synthase pathway.
AB  - Nitric oxide (NO) produced from L-arginine by NO synthases (NOS) is a transmitter
      known to be involved in diverse biological processes, including immunomodulation,
      neurotransmission and blood vessel dilatation. We describe a novel role of NO as
      a signaling molecule in post-transcriptional gene regulation. We demonstrate that
      induction of NOS in macrophage and non-macrophage cell lines activates RNA
      binding by iron regulatory factor (IRFs), the central trans regulator of mRNAs
      involved in cellular iron metabolism. NO-induced binding of IRF to iron
      responsive elements (IRE) specifically represses the translation of transfected
      IRE-containing indicator mRNAs as well as the biosynthesis of the cellular iron
      storage protein ferritin. These findings define a new biological function of NO
      and identify a regulatory connection between the NO/NOS pathway and cellular iron
      metabolism.

PMID- 7504628
TI  - The ontogeny of allele-specific methylation associated with imprinted genes in
      the mouse.
AB  - We have investigated the DNA methylation patterns in genomically imprinted genes
      of the mouse. Both Igf2 and H19 are associated with clear-cut regions of allele
      specific paternal modification in late embryonic and adult tissues. By using a
      sensitive PCR assay, it was possible to follow the methylation state of
      individual HpaII sites in these genes through gametogenesis and embryogenesis.
      Most of these CpG moieties are not differentially modified in the mature gametes
      and also become totally demethylated in the early embryo in a manner similar to
      non-imprinted endogenous genes. Thus, the overall allele-specific methylation
      pattern at these sites must be established later during embryogenesis after the
      blastula stage. In contrast, sites in an Igf2r gene intron and one CpG residue in
      the Igf2 upstream region have allele-specific modification patterns which are
      established either in the gametes or shortly after fertilization and are
      preserved throughout pre-implantation embryogenesis. These studies suggest that
      only a few DNA modifications at selective positions in imprinted genes may be
      candidates for playing a role in the maintenance of parental identity during
      development.

PMID- 7504631
TI  - Inhibitors of nitric oxide synthase enhance rat ileum contractions induced by
      ricinoleic acid in vitro.
AB  - The effects of NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L
      arginine (L-NMMA), inhibitors of nitric oxide (NO) synthase, were studied on
      ricinoleic acid-evoked contractions in rat isolated ileum. Ricinoleic acid (10(
      5) to 10(-4) M) caused a concentration-dependent contraction. Addition of L-NAME
      (30-300 microM) or L-NMMA (30-300 microM) to the Tyrode's solution increased in a
      concentration-dependent fashion the amplitude of the ricinoleic acid-evoked
      responses. L-Arginine (900 microM), a natural substrate of NO synthase, but not D
      arginine (900 microM), counteracted the effect of L-NAME (300 microM). The
      potentiating effect of L-NAME was also prevented by sodium nitroprusside (0.1-1
      microM), a generator of NO. These results provide evidence that endogenous NO may
      modulate the contraction of rat ileum induced by ricinoleic acid. As the
      contraction induced by ricinoleic acid is not blocked by tetrodotoxin (0.6 and
      6.0 microM) the contractile effect of ricinoleic acid results mainly from a
      direct action on the smooth muscle.

PMID- 7504632
TI  - Babesia divergens: characterization of a 17-kDa merozoite membrane protein.
AB  - Large amounts of viable merozoites were purified from in vitro cultures of
      Babesia divergens by a two-step sieving procedure. A monoclonal antibody produced
      against B. divergens merozoites, mAb DG7, stained the merozoite plasma membrane
      and an intra-parasitic linear organelle in indirect immunofluorescence.
      Immunogold labeling in electron microscopy demonstrated that the antigen
      recognized by mAb DG7 was localized just beneath the merozoite plasma membrane.
      Immunoprecipitations of metabolically labeled ([35S]methionine) B. divergens
      antigens showed that the epitope recognized by mAb DG7 was present on a 17-kDa
      polypeptide (Bd17) and was shared in all B. divergens geographical isolates
      tested so far. Bd17 was always present in the in vitro culture supernatants of
      all these isolates. Furthermore, Triton X-114 phase separation of babesial
      antigens demonstrated the hydrophilic character of Bd17 which suggests that it is
      an extrinsic protein present on the cytosol side of the parasite membrane. When
      added to the culture medium, mAb DG7, purified from ascite fluids, drastically
      altered the growth of the parasite with concentrations inhibiting 50% of
      development (IC50) ranging between 16.6 and 26.1 micrograms/ml).

PMID- 7504634
TI  - Neovascular complications after central retinal vein occlusion.
AB  - An 8-year retrospective study of patients suffering a central retinal vein
      occlusion (CRVO) was undertaken to study secondary new vessel formation and
      whether pathologies known to predispose to CRVO influenced the occurrence of
      these neovascular complications and their responsiveness to treatment. Seventy
      three patients were studied. Ocular neovascularisation had occurred in 60%. More
      specifically 39% developed neovascular glaucoma. Panretinal photocoagulation
      produced regression in only 37% of those with established neovascularisation and
      was unsuccessful in preventing neovascularisation in five patients treated
      prophylactically. Patients with pre-existing primary open angle glaucoma (POAG)
      were statistically more likely to develop ocular neovascularisation (p = 0.02),
      which was also less responsive to laser therapy (p = 0.02). Adequate prior
      glaucoma therapy did not protect against this enhanced complication rate. It was
      concluded that POAG is a significant risk factor for developing ocular
      neovascularisation after CRVO which will be refractory to laser therapy.

PMID- 7504633
TI  - Giardia lamblia: absence of cyst antigens and reduced secretory vesicle formation
      and bile salt uptake in an encystation-deficient subline.
AB  - Encystation of Giardia lamblia entails the appearance of a number of new
      antigens, as well as formation of a novel class of large encystation-specific
      secretory vesicles (ESV) that transport stage-specific proteins to the nascent
      cyst wall. The monoclonal antibody GCSA-1, which was raised against purified cyst
      walls, recognizes protein species of approximately 26-46 kDa that are regulated
      by exposure to bile (plus lactic acid) and alkaline pH, the factors that induce
      encystation. The GCSA-1 epitope is maximally expressed after approximately 14 hr
      of encystation and localizes to the interior, but not the membrane of the ESV as
      shown by frozen section immunoelectron microscopy. To further understand the
      process of encystation, we compared two sublines of strain WB that differ in
      their ability to encyst in vitro. Water-resistant cysts were not detected in
      subline A6 under conditions in which subline C6 formed approximately 2 x 10(5)
      cysts/ml. Moreover, subline A6 did not form ESV efficiently or detectably express
      antigens recognized by mAb GCSA-1 or by polyclonal anti-cyst sera. Finally,
      uptake of the bile salt taurocholate by A6 was reduced 4- to 20-fold, compared
      with that of C6, although transport by both strains was sodium-dependent and
      regulated by bile salt starvation. The decrease in bile salt uptake by A6 may be
      related to its defect in encystation.

PMID- 7504635
TI  - Regulation of astrocytic tenascin by basic fibroblast growth factor.
AB  - Extracellular matrix (ECM) molecules have been implicated in the regulation of
      neuronal adhesion and neurite outgrowth both during development and after injury.
      It has been demonstrated in our laboratory that astrocytes are heterogeneous in
      expression of the ECM molecule tenascin. High-tenascin astrocytes have a reduced
      ability to support neurite outgrowth. In addition, astrocytes treated with
      exogenous basic fibroblast growth factor (bFGF) supported reduced neuronal growth
      and adhesion. In the current study, the hypothesis was tested that bFGF could
      increase the expression of tenascin by these cells. Basic FGF was added to
      cultures of rat cerebral cortical astrocytes at concentrations of up to 30 ng/ml,
      concentrations shown to have a significant effect on neuronal adhesion. Tenascin
      levels were evaluated by Western blot analysis of both cell extracts and
      conditioned media and also by immunocytochemistry techniques. Tenascin levels
      began to increase after 24-48 hr and continued to increase throughout 8 days in
      culture. The increase in tenascin was concentration-dependent, with the largest
      increase seen at 5 ng/ml bFGF. Tenascin production was increased approximately
      5.5-fold in serum-containing medium but only about 2-fold in serum-free medium.
      When heparin (10 micrograms/ml) was included along with bFGF in serum-free
      medium, tenascin production was further enhanced. The bFGF treatment was
      discontinued after 8 days, and the cells were maintained for an additional 8 days
      in culture. Tenascin levels returned to control values, demonstrating that the
      bFGF effect is transient. It is our hypothesis that the action of bFGF during
      injury may evoke the induction of tenascin on astrocytes, thereby reducing
      regeneration in the central nervous system.

PMID- 7504636
TI  - Cell-cell interactions affect the accumulation of a cytokeratin-like protein
      during lens fiber development.
AB  - Extracellular matrix proteins were presented in culture to postmitotic,
      epithelial precursors of chick lens fiber cells as rigid, planar surfaces or
      malleable gels. Their ability to maintain and promote differentiated
      characteristics was judged by tritiated thymidine incorporation, immunologic
      detection of a cytokeratin-like protein (CP49) which accumulates during lens
      fiber development, and the formation of multicellular aggregates known as
      lentoids. Regardless of their composition, planar substrates stimulated the
      reentry into the cell cycle by promoting cell spreading. Laminin- and type IV
      collagen-coated surfaces facilitated monolayer growth and no appreciable
      accumulation of CP49. Thin films of Matrigel, which initially stimulated cell
      division, eventually promoted the formation of extensive lentoids, multicellular
      aggregates exhibiting many morphologic and biochemical properties of lens fibers.
      Malleable gels of Matrigel, however, inhibited cell division and immediately
      allowed the cells to begin lentoid formation. Culture conditions which favored
      lentoid formation also showed greatly enhanced levels of CP49 accumulation. In
      addition, lentoids were also shown to accumulate an integral membrane protein
      (MIP26) which is present in communicating junctions between neighboring fiber
      cells. These studies indicate that increased cell associations within forming
      lentoids may influence the progression of lens fiber terminal differentiation in
      vitro.

PMID- 7504637
TI  - Embryonic expression of human keratin 18 and K18-beta-galactosidase fusion genes
      in transgenic mice.
AB  - During embryogenesis, EndoB, the mouse form of human keratin 18 (K18), is
      expressed in a complex spatial and temporal pattern in various embryonic
      epithelia. We have compared the expression of transgenic human K18 to the
      endogenous mouse homolog and to the coexpressed, complementary keratin 8 homolog,
      EndoA, during postimplantation mouse embryogenesis and fetal development in order
      to determine the developmental expression pattern of the human gene in a mouse
      environment. The tissue distribution of K18 protein was identical to that of
      endogenous EndoB in both 7.5- and 13.5-day-old embryos, except for certain heart,
      eye, and extraembryonic mesodermal tissues in which K18 was not detected. These
      results indicate that the 10-kb K18 gene specifies appropriate developmental
      expression in the mouse and support previously reported differences in K18
      expression in human and mouse fetal heart. We have also compared the expression
      patterns of K18 to a series of constructions that utilize the Escherichia coli
      gene for beta-galactosidase (lacZ) as a reporter gene. Some of these
      constructions were regulated correctly in embryos during development of the germ
      layers. However, none was expressed consistently in extraembryonic or in adult
      tissues. Analysis with methylation-sensitive restriction enzymes revealed that
      hypermethylation of the CpG-rich prokaryotic reporter gene was not the cause of
      its silence in adult transgenic liver. However, the repressed state of K18-LacZ
      transgenes in adult liver was correlated with a different chromatin state that
      lacked diagnostic DNase hypersensitive sites found in K18 transgenic liver.
      Expression of the lacZ reporter gene did not accurately reflect the developmental
      pattern of K18 even in constructions that used all available K18 sequences. We
      conclude that in these contexts, the lacZ gene was not a developmentally neutral
      reporter gene.

PMID- 7504638
TI  - Sensorimotor development in cerebral-palsied infants assessed with the Uzgiris
      Hunt scales.
AB  - The cognitive development of a group of 89 cerebral-palsied infants, aged six to
      24 months, was investigated using the Uzgiris-Hunt scales. The results were
      compared with normative data for the Italian population and with data obtained in
      a group of low-risk term and preterm infants, 11 to 13 months old. The test was
      easy to carry out, even on infants with a severe motor impairment. The majority
      of the infants showed cognitive delay on most of the scales. Tetraplegic patients
      performed significantly worse than those with diplegia or hemiplegia. There were
      no differences between preterm and term infants, for either normal or cerebral
      palsy groups, if age was corrected for preterm birth. Sensorimotor development
      appeared to be organized similarly for cerebral-palsied infants and normal
      controls; however, these data raise the question of the role of action in early
      cognitive development.

PMID- 7504641
TI  - Residual myelotoxicity of lindane in mice.
AB  - Lindane (gamma-1,2,3,4,5,6-hexachlorocyclohexane), a widely used insecticide, may
      be found at low concentrations in the human diet. Male B6C3F1 mice given lindane
      daily at doses of 20 and 40 mg/kg body wt by gavage in corn oil for 3 days had
      suppressed bone marrow cellularity, erythrocyte precursors, granulocyte
      macrophage progenitor cells (CFU-GM), and residual progenitor cell damage, which
      could be demonstrated by two whole-body irradiations (WBI) at 200 rads. Lindane
      exposure for 10 consecutive days at doses of 0, 10, or 20 mg/kg did not cause
      clinical abnormality or changes in body weights, but there were dose-dependent
      decreases in marrow cellularity, in more pluripotent stem cells and in committed
      CFU-GMs, which returned to control values by 4 weeks. These mice were then
      subjected to two 100-rad exposures of WBI at 4 and 9 weeks following cessation of
      lindane treatment. This level of irradiation caused only a transient drop in
      number of marrow progenitor cells. Control and lindane-exposed mice were examined
      at 1 and 6 weeks following the last irradiation, which was 10 and 15 weeks
      following the final lindane exposure. The lindane-exposed mice had lower
      progenitor cell numbers and slower recovery from the irradiation. These results
      indicate that lindane has significant myelotoxicity in mice and short-term
      lindane exposure can induce residual progenitor cell damage that can be
      demonstrated by subsequent irradiation.

PMID- 7504640
TI  - Hepatic failure leads to lethality of chlordecone-amplified hepatotoxicity of
      carbon tetrachloride.
AB  - Chlordecone (Kepone) amplification of CCl4 toxicity occurs at small, nontoxic
      levels of chlordecone and CCl4 and results in highly increased irreversible
      hepatotoxicity culminating in lethality. Although it is generally assumed that
      CCl4 lethality is due to hepatic failure, no definitive studies are available in
      the literature bridging massive liver failure and death. The present studies were
      designed to evaluate whether hepatic failure is the cause of the lethality during
      chlordecone-amplified CCl4 toxicity. Male Sprague-Dawley rats were maintained on
      control or a chlordecone (10 ppm) diet for 15 days and injected with CCl4 (100
      microliters/kg, ip) on Day 16. Rats were killed at 0, 6, 12, 24, 36, and 48 hr
      after CCl4 challenge. Hepatic failure was evaluated by measuring plasma glucose,
      ammonia, bilirubin, aspartate transaminase (AST), alanine transaminase (ALT),
      sorbitol dehydrogenase (SDH), hepatic ATP, glycogen, and by histological and
      histomorphometric analyses. Plasma creatinine, urea, and kidney histopathology
      were also assessed for possible renal injury. As expected CCl4 administration to
      chlordecone-pretreated rats resulted in 20% lethality by 36 hr, which progressed
      with time, and all rats died within 72 hr. A significant and progressive
      hypoglycemia was observed with a 60% reduction in plasma glucose at 48 hr.
      Hepatic glycogen content dropped precipitously. Similarly, hepatic ATP levels
      remained suppressed (80% of control) at all the time points studied. Plasma
      ammonia levels were significantly elevated, and by 48 hr, a threefold increase
      was observed. Plasma ALT, AST, SDH, and bilirubin increased progressively until
      the death of rats receiving the chlordecone + CCl4 combination.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7504642
TI  - [Sensory fibers sensitive to capsaicin can modulate secretion of the duodenal
      mucus. A morphometric study in rats].
AB  - Many in vitro and in vivo models have been used to study the modulation of
      intestinal mucosecretion. In such studies, quantification of mucus secretion is
      usually difficult, due to several technical problems. Whether sensory mechanisms
      participate in the modulation of intestinal mucosecretion remains unknown. The
      development and assessment of a morphometric method with computer assisted image
      analysis that allows to detect and quantitate mucin secretion by duodenal goblet
      cells are reported. Using this method, the secretory effect of pilocarpine on
      villus and crypt goblet cells was confirmed. We also determined whether sensory
      neurons can regulate intestinal mucosecretion by using capsaicin, a vegetal
      neurotoxin specific of a subpopulation of afferent primary sensory neurons.
      Intravenous capsaicin administration (10 micrograms/kg) increased mucus secretion
      by the goblet cells of the duodenal crypts. This suggests that sensory neurons
      may modulate duodenal mucin secretion. The "local effector function" of these
      neurons might be involved, in part through the release of substance P because
      exogenous substance P was able to increase mucin excretion by goblets cells of
      duodenal villi. Substance P, however, did not exactly mimic the capsaicin
      effects, suggesting that other factors were involved.

PMID- 7504643
TI  - Nitric oxide synthase distribution in the rat intestine: a histochemical
      analysis.
AB  - BACKGROUND: Nitric oxide is an inhibitory transmitter of nonadrenergic,
      noncholinergic neurons and is purported to be an endothelium-derived relaxant
      type factor in the mammalian gut. This study aimed to provide a complete report
      on the distribution of NO synthase in the rat small and large intestine. METHODS:
      NO synthase was visualized histochemically through this enzyme's reduced
      nicotinamide adenine dinucleotide phosphate diaphorase activity and the
      distribution of staining within the gut wall. RESULTS: The presence of NO
      synthase activity in myenteric neurons and their efferents to the circular muscle
      was confirmed. The largest proportion of stained cells per ganglion was found in
      the ileum, and the smallest proportion was in the colon. Stained neural elements
      were also found within the submucosa throughout the intestine. Stained cells
      within the myenteric and submucous nerve plexi displayed both type I and type II
      morphologies, with the latter being more numerous. In addition to neural
      staining, submucosal arterioles showed a regular pattern of small patches of
      staining unrelated to any perivascular innervation. CONCLUSIONS: These findings
      indicate an extensive neural and vascular localization of NO generation potential
      throughout the wall of the rat intestine, thus providing a structural basis for
      the functional diversity of NO.

PMID- 7504639
TI  - Neurodevelopmental profile at five years of children born at < or = 32 weeks
      gestation.
AB  - Sixty children born preterm (gestational age < or = 32 weeks) and 60 control
      children matched by sex, and socio-economic and educational status of the parents
      were followed prospectively to the age of five years. Neurodevelopmental problems
      were surveyed by a detailed neurological and neuropsychological test battery, and
      by ophthalmological and hearing examinations. All except one of the preterm
      children with major disability had motor, visual-spatial and visual problems. The
      most frequent neurodevelopmental abnormalities encountered among preterm children
      without major disability were motor problems--emerging as gross and fine motor
      and/or visual-motor difficulties--and visual-spatial problems. Language
      difficulties were not associated with hearing problems. Among those without major
      disability, visual-spatial difficulties and ophthalmological problems seldom
      emerged simultaneously.

PMID- 7504644
TI  - Interleukin 1 beta-induced increase in substance P in rat myenteric plexus.
AB  - BACKGROUND: Substance P (SP) is increased in the inflamed intestine of
      Trichinella spiralis-infected rats, but the underlying mechanism is unknown.
      Interleukin 1 beta (IL-1 beta) messenger RNA and protein is expressed in the
      longitudinal muscle-myenteric plexus (LM-MP) of this model. Thus, the purpose of
      the study was to examine the ability of human recombinant IL-1 beta (hrIL-1 beta)
      to increase SP in LM-MP preparations from the intestine of noninfected rats.
      METHODS: LM-MP preparations were incubated with hrIL-1 beta, and immunoreactive
      SP (IR-SP) was assessed in the tissues by radioimmunoassay or
      immunohistochemistry. RESULTS: hrIL-1 beta increased IR-SP in the tissue in a
      time- and concentration-dependent manner, being maximal after 6 hours at a
      concentration of 10 ng/mL. The IR-SP could be depleted by scorpion venom, and
      immunohistochemistry revealed increased staining for SP within nerves of the LM
      MP. The action of IL-1 beta was dependent on protein synthesis, was receptor
      mediated, and was not due to endotoxin contamination of the cytokine preparation.
      CONCLUSIONS: hrIL-1 beta stimulates the synthesis of SP in myenteric nerves of
      rat intestine.

PMID- 7504645
TI  - Localization of the cystic fibrosis transmembrane conductance regulator in human
      bile duct epithelial cells.
AB  - BACKGROUND: Liver dysfunction is a common manifestation of cystic fibrosis (CF),
      a disease caused by mutations affecting the CF transmembrane conductance
      regulator (CFTR). The aim of this study was to examine the distribution and role
      of CFTR in liver. METHODS: CFTR messenger RNA was detected in cryosections of
      human liver by in situ hybridization. CFTR immunoreactivity was detected using
      antibodies raised against two CFTR peptides. RESULTS: The predominant site of
      CFTR messenger RNA and immunoreactivity in liver is the intrahepatic bile duct.
      CFTR is not detected in hepatocytes of normal liver or in livers exhibiting bile
      duct proliferation. Within bile duct cells, CFTR is localized at or near the
      apical plasma membrane. CONCLUSIONS: The apical localization of CFTR in bile duct
      cells suggests a model explaining how the CFTR-associated Cl- channel contributes
      to normal biliary secretion. This model suggests that if CFTR expression could be
      promoted in intrahepatic duct cells by somatic gene therapy, this might prevent
      the occurrence of liver disease in CF.

PMID- 7504646
TI  - Prostate cancer: who to screen, and what the results mean.
AB  - Long-term survival of patients with prostate cancer is inversely proportional to
      the extent of disease at diagnosis. Patients with known risk factors for the
      development of prostate cancer may be particularly well-suited for screening. The
      combination of digital rectal exam and serum prostate specific antigen (PSA)
      level results in higher cancer detection rates and positive predictive values
      than either test alone. PSA levels < 4 ng/ml are unlikely to reflect cancer,
      whereas patients with PSA levels > 10 ng/ml are presumed to have prostate cancer
      until proven otherwise. Using PSA density or PSA rate of change can increase the
      diagnostic accuracy of the serum PSA level in the 4 to 10 ng/ml range. Despite
      the ability of screening tests to detect prostate cancer, no trial has tested the
      impact of screening on survival.

PMID- 7504647
TI  - [Prostatic specific antigen--tumor markers in prostate cancer].

PMID- 7504648
TI  - Proliferating cell nuclear antigen in endometrial adenocarcinomas of endometrioid
      type correlated with histologic grade, stage, previous hormonal treatment, and
      survival.
AB  - Only a small number of endometrial carcinomas have been examined for
      proliferating cell nuclear antigen. The results indicate that a high
      proliferating cell nuclear antigen content correlates with a poor prognosis. One
      hundred eight endometrial carcinomas of endometrioid type were examined with the
      monoclonal antibody PC10 (48 tumors from postmenopausal estrogen users and 60
      tumors from nonusers). The PC10 content was weakly but significantly correlated
      with mitotic count and architectural grade, but not with nuclear grade, stage, or
      survival. PC10 values in estrogen users were much lower (median, 14%) than in
      nonusers (median, 26%); the difference was independent of histologic grade and
      stage. After a median follow-up of 30 months (range, 12 to 66 months) 17 patients
      had died. The cause of death was established as cancer in only nine cases. No
      overall difference in PC10 values existed between survivors and nonsurvivors.
      However, if only the estrogen nonusers were examined the survivors showed a mean
      PC10 value of 27%, while the nonsurvivors showed a mean PC10 value of 45%. The
      present study indicates that carcinomas from patients with and without previous
      hormonal treatment are different with regard to their PC10 content. The
      quantitative and qualitative estimates of PC10 correlated well.

PMID- 7504649
TI  - Sarcomatoid collecting duct carcinoma: a clinicopathologic and
      immunohistochemical study of five cases.
AB  - Sarcomatoid renal cell carcinoma is a well-known entity, but sarcomatoid
      collecting duct carcinoma has not been reported. We recently encountered five
      cases. The patients were men whose ages ranged from 59 to 82 years (mean age, 68
      years). All presented with gross hematuria and three had abdominal fullness.
      Tumor size ranged from 6 to 9 cm in greatest dimension. The Fuhrman's nuclear
      grade of the carcinomatous components was 3 in three cases and 4 in two. The
      sarcomatoid areas were composed of pleomorphic spindle cells forming a malignant
      fibrous histiocytomatous pattern in four cases and a fibrosarcomatous pattern in
      one. The immunohistochemical findings in the carcinomatous and sarcomatoid
      components were identical. Wide-spectrum anti-cytokeratin cocktail, epithelial
      membrane antigen, and vimentin antibodies demonstrated immunoreactivity, while
      Leu-M1 did not react in all five cases. Three of the five tumors were positive
      for Ulex europaeus agglutinin I lectin. One sarcomatoid carcinoma reacted with
      monoclonal antibody to high molecular weight keratins, and all five tumors
      reacted with a monoclonal antibody to low molecular weight keratins. Two patients
      died at 5 months and 13 months after diagnosis, two are alive with metastatic
      disease at 1 and 14 months, and one is alive with no evidence of disease at 36
      months.

PMID- 7504650
TI  - Congenital sarcoma in the terminal ileum histologically resembling clear cell
      sarcoma of the kidney: a case report with an immunohistochemical study.
AB  - We report a case of a newborn female with a rare tumor, a congenital sarcoma,
      presenting as an abdominal mass. Laparotomy demonstrated the tumor arising from
      the wall of the terminal ileum. Histologically, the tumor tissue was
      indistinguishable from clear cell sarcoma of the kidney and was composed of
      proliferating cells with poorly stained cytoplasm divided into nests or cords by
      arborizing vasculature. Immunohistochemical staining revealed that the neoplastic
      cells had a phenotype similar to metanephric blastemal cells of fetal kidney, ie,
      positive for vimentin and CD24 but negative for cytokeratin and CD9. The results
      suggest that this congenital tumor may originate from primitive mesenchymal cells
      phenotypically related to cells present in the fetal kidney.

PMID- 7504651
TI  - Pathology of symptomatic microsporidial (Encephalitozoon hellem) bronchiolitis in
      the acquired immunodeficiency syndrome: a new respiratory pathogen diagnosed from
      lung biopsy, bronchoalveolar lavage, sputum, and tissue culture.
AB  - Encephalitozoon hellem is a recently described microsporidian associated with an
      expanding spectrum of clinical presentations in patients with the acquired
      immunodeficiency syndrome (AIDS). It is morphologically similar to
      Encephalitozoon cuniculi, a microsporidian infection of mammals and some avians,
      and their differentiation rests on biochemical and antigenic analyses. This
      report describes a patient previously diagnosed with keratoconjunctivitis due to
      E hellem who subsequently was found to have respiratory tract microsporidiosis by
      sputum cytology. He subsequently developed pulmonary symptoms and a left lower
      lobe interstitial infiltrate. A bronchoalveolar lavage and transbronchial biopsy
      revealed microsporidial bronchiolitis, and the etiologic agent was identified as
      E hellem using an immunofluorescent antibody technique. Lavage fluid was
      successfully cultured in monkey kidney cells, and cultivated E hellem organisms
      were studied using immunohistochemistry as well as scanning and transmission
      electron microscopy. The pathologic features of this newly described cause of
      protozoal bronchiolitis, the role of immunofluorescent antibody examination and
      in vitro tissue culture for species-specific diagnosis, and the significance of
      microsporidial pulmonary infections in AIDS patients are discussed.

PMID- 7504652
TI  - Occult axillary lymph node metastases in "node-negative" breast carcinoma.
AB  - The presence of occult axillary nodal metastases was evaluated in 159 patients
      with "node-negative" invasive breast carcinoma. Multiple additional levels of the
      lymph nodes were examined with hematoxylin-eosin staining and keratin
      immunostaining. Occult nodal metastases were detected in 50 (31%) patients; of
      these, 28 (17%) were detectable by hematoxylin-eosin stain alone, while the other
      22 (14%) consisted of mostly single cells or very small clusters and required
      immunostaining for detection. The size of the metastatic deposit was < or = 0.2
      mn in 31 (19%) patients and greater than 0.2 mm in 19 (12%) patients. Occult
      nodal metastasis correlated with the presence of peritumoral lymphatic invasion
      (P = .02) and was seen more frequently with larger tumor size, increased
      microvasculature, and aneuploidy. As a group occult metastases had no significant
      prognostic impact. However, patients with metastases measuring greater than 0.2
      mm had significantly worse recurrence (P = .02), disease-free survival (P = .04),
      and overall survival (P = .07) rates; those with metastases detectable by
      hematoxylin-eosin stain alone also had a less favorable, although not
      significant, outcome. In contrast, patients with occult metastases that were < or
      = 0.2 mm or that were detected only by immunostaining had a survival rate
      comparable to and in fact slightly higher than that of the group without occult
      metastasis; 23 of these patients were without recurrence after a median follow-up
      of 11 years. Extension into perinodal soft tissue was an unfavorable feature. In
      a multivariate analysis peritumoral lymphovascular invasion and increased
      microvasculature were the most important prognostic parameters, and the presence
      of occult metastases greater than 0.2 mm was no longer significant. Our data
      suggest that occult metastases < or = 0.2 mm, especially those consisting of
      single cells, do not add useful prognostic information, and immunohistochemical
      studies to detect them are probably unnecessary. Larger metastases and extranodal
      involvement may have important prognostic value, but in this study they accounted
      for only 20% of patients who had recurrences or 6% of the total population. This
      underscores the importance of using more than one prognostic parameter in
      evaluating breast carcinoma.

PMID- 7504653
TI  - Mammary ductal foam cells: macrophage immunophenotype.
AB  - Mammary ductal foam cells are present in normal breast tissue as well as in a
      number of breast diseases. Such foam cells tend to be in particular abundance
      with fibrocystic changes of the breast. Foam cells may appear within duct lumens
      or plastered in cohesive masses along duct walls, simulating an epithelial
      structure. The nature and origin of these innocuous-appearing cells, based on
      morphologic studies, remain a controversy, for they appear to be of epithelial
      derivation. This study was undertaken to determine the nature of intraductal
      "foam" cells and their origin in the breast. Nine cases of adult fibrocystic
      disease were examined immunohistochemically with antibodies to cytokeratins (Mak
      6, Cam 5.2), leukocyte common antigen, and the following macrophage antibodies:
      KP-1 (CD68), HAM 56, and MAC 387. The lysozyme and alpha-1-antitrypsin content of
      foam cells also was studied. The immunohistochemical data in this study confirm
      the macrophage character of these foam cells, which are positive for CD68, HAM
      56, and MAC 387, lysozyme, and alpha-1-antitrypsin and negative for leukocyte
      common antigen and cytokeratins.

PMID- 7504654
TI  - Tenascin expression in prostatic hyperplasia, intraepithelial neoplasia, and
      carcinoma.
AB  - The expression of tenascin, an extracellular matrix glycoprotein, was studied in
      three human prostatic carcinoma cell lines by Northern and Western blot analyses
      and in human prostate tissues by immunohistochemistry and Western blot analysis.
      All three carcinoma cell lines expressed tenascin mRNA and protein, which were
      found predominantly in secreted form in culture supernatant. By
      immunohistochemistry, fetal prostatic tissue showed strong and diffuse tenascin
      immunoreactivity around developing glands. Normal adult prostatic tissue revealed
      only focal, scant periglandular and stromal immunoreactivity around acini and
      ducts. Most cases of hyperplasia and intraepithelial neoplasia showed variable
      periglandular immunostaining. Tenascin periglandular staining with diffuse
      stromal extension was noted with all grades of adenocarcinoma; however, the
      intensity was variable and appeared unrelated to the histologic grade. Metastatic
      prostatic carcinoma showed strong immunoreactivity in lymph nodes and bone marrow
      samples, with only weak reactivity of the normal connective tissue framework in
      both tissues. Western blot analysis of prostatic hyperplasia and carcinoma
      demonstrated the large and small isoforms of tenascin. These findings suggest a
      prominent role for tenascin in stromal alterations associated with both benign
      and malignant prostatic epithelial growth processes.

PMID- 7504656
TI  - Inhibition of metastatic cell colonization in murine lungs and tumor-induced
      morbidity by non-peptidic Arg-Gly-Asp mimetics.
AB  - The spreading and colonization of tumor cells require their migration to
      metastatic sites via blood vessels. To penetrate blood-vessel walls, cells,
      including malignant ones, must recognize and associate with the sub-endothelium
      extracellular matrix (ECM) and its glycoproteins. Recognition of ECM
      glycoproteins, such as fibronectin (FN) and vitronectin (VN), is mediated by
      integrin receptors expressed on various cell types, including platelets,
      leukocytes and tumor cells. The Arg-Gly-Asp (RGD)-containing peptide, a major
      adhesive ligand of ECM, is present in various plasma and matrix glycoproteins,
      such as FN and VN. Non-peptidic mimetics of RGD, consisting of carboxylate and
      guanidinium groups of Asp and Arg divided by a linear atom spacer, express a high
      affinity for the alpha IIb-beta 3 integrin and inhibit platelet aggregation.
      Herein, the ability of RGD mimetics to inhibit adhesive interactions between
      tumor cells and RGD, and tumor progression in vivo, was examined. RGD-containing
      peptides and the RGD mimetic, compound SF-6,5, but not the Arg-Gly-Glu (RGE)
      peptide or the corresponding mimetic, specifically inhibited B16-F10 melanoma
      cell adhesion to immobilized VN and FN. Daily administration in vivo of SF-6,5 to
      mice inhibited the formation of B16-F10 colonies in experimental and spontaneous
      models of metastases. Moreover, SF-6,5 could prevent mouse death caused by
      massive colonization of tumor cells in the lungs. The therapeutic effect of RGD
      containing peptides on tumor metastasis formation was marginal, probably due to
      the small amounts used, and its susceptibility to proteolysis in situ. Thus, non
      peptidic mimetics of small adhesive epitopes may provide a novel therapeutic tool
      to prevent an adverse pathological event involving integrin-dependent cell-cell
      and cell-ECM interactions.

PMID- 7504655
TI  - Septic shock: pathogenesis and treatment.
AB  - Septic shock is the host's inflammatory response to infection. There are multiple
      endogenous mediators responsible for the pathogenesis of septic shock. Cytokines,
      nitric oxide and prostaglandins are some of the major mediators. The term sepsis
      syndrome allows for an earlier diagnosis and treatment. Management of septic
      shock is focused in maintaining hemodynamic stability and an adequate oxygen
      delivery and utilization. Careful attention to each organ-system is of paramount
      importance to prevent complications and improve outcome. Experimental therapies
      to modulate the inflammatory response are promising.

PMID- 7504657
TI  - Alterations of the p53 tumor-suppressor gene in transformed mouse liver cells.
AB  - Mutational inactivation of p53, a potential tumor-suppressor gene, has been found
      in many tumors of humans as well as rodents. The p53 status in normal and
      transformed mouse liver cell lines has, however, not been investigated. We
      examined possible point mutations and compared mRNA and protein expression of the
      p53 gene in normal vs. transformed mouse liver cells. The transformed cells
      studied included lines spontaneously transformed by sub-culture, virally
      transformed by simian virus 40 (SV40), and chemically transformed by N-methyl-N
      nitro-N-nitrosoguanidine (MNNG) or methylcholanthrene epoxide (MC). A
      heterozygous G-->A point mutation at codon 241, position 1, of p53 was detected
      in MNNG-transformed cells after screening of 5 evolutionarily conserved regions
      where mutation hot-spots are clustered. The mutation causes a gly-->arg
      substitution. No mutations were found in normal or other transformed cells. The
      steady-state levels of p53 mRNA were decreased in chemically transformed (both
      MNNG- and MC-transformed) cells. Elevated levels of p53 protein were found in
      spontaneously transformed and SV40-transformed cells, an observation that may
      reflect a longer half-life of the protein, as has been shown in other transformed
      lines. The low level of the p53 protein in MC-transformed cells may result from
      transcriptional depression of the p53 gene. We conclude from these data that
      abnormal p53 status, such as point mutation or altered expression, may play a
      role during the malignant transformation of mouse liver cells.

PMID- 7504658
TI  - Biochemical and immunological characterization of the human carcinoma-associated
      antigen MH 99/KS 1/4.
AB  - We have characterized the 38-kDa transformation-associated membrane glycoprotein
      MH 99, whose expression is highly elevated in many epithelial malignancies. A
      spontaneous cleavage of MH 99 into a 32- and a 6-kDa chain in some carcinoma cell
      lines was recently shown. Sequence homologies to nidogen, a matrix-adhesion
      molecule, support the suggestion of a receptor-like function. In this study, we
      characterized biochemical and immunogenic aspects of MH 99. Transformed
      epithelial cell lines which do not spontaneously cleave MH 99 were exposed to 8
      proteases with distinct specificities. Each of the enzymes produced similar
      specific fragmentation into chains of about 30 to 32 and 6 kDa, indicating a
      characteristic cleavage site of MH 99. The fragments were not distinguishable
      from those in carcinoma cells showing spontaneous cleavage of MH 99. The specific
      fragmentation depends on the localization in intact membranes and is not shared
      by other membrane proteins. N-glycosylation of MH 99 of about 4 kDa was
      exclusively found on the 32-kDa fragment. Characterization of antigenic epitopes
      was performed using 16 different monoclonal antibodies (MAbs). Only 2 independent
      determinants were found. One is located on the 32-kDa chain and is recognized
      only by the MM 104 MAb. The other 15 antibodies bind to a dominant epitope on the
      6-kDa fragment which can be divided into 3 overlapping sub-epitopes. The unique
      features of MH 99 indicate that its immunogenic epitopes are mainly located at
      its 6-kDa chain, and support the suggestion of a transformation-associated cell
      surface receptor which might be proteolytically regulated.

PMID- 7504659
TI  - Ontogenic development of murine fetal thymocytes is accelerated by 3,3',4,4'
      tetrachlorobiphenyl.
AB  - Polychlorinated hydrocarbons such as biphenyls or dioxins interfere with cellular
      processes by gene induction via ligand-activated binding of the cytosolic Ah
      receptor to specific DNA elements. The thymus is a target organ for these
      processes and immunosuppression a hallmark of polychlorinated hydrocarbon
      toxicity. Using flow cytometry we analysed the development of thymocytes in fetal
      thymus organ cultures (FTOC) exposed to tetrachlorobiphenyl (TCB) for up to one
      week. We show that exposure to TCB changes the normal developmental pathways of
      fetal thymocytes within days. Overall fewer thymocytes are found in TCB-treated
      cultures from day 4 on, and significantly more CD8 positive thymocytes are
      detectable. These cells express the T-cell receptor, but not heat-stable antigen
      or IL2-receptor, giving them a mature phenotype. Moreover, relatively more
      CD4/CD8 double-negative thymocytes express CD44, a molecule involved in
      lymphocyte-epithelial interaction. We suggest that, at least for the CD8 single
      positive thymocyte population, maturation is accelerated, and this may be due to
      TCB interference with physiological thymocyte-epithelial interactions.

PMID- 7504660
TI  - The in vitro action of FK 565, bleomycin and cyclosporin A on different cell
      populations, with respect to the release of GM-CSF in the mouse.
AB  - The experimental immunostimulatory tripeptide FK 565, the anti-tumor antibiotic
      Bleomycin and the immunosuppressive agent Cyclosporin A were examined for their
      in vitro effects on granulocyte-macrophage colony stimulating factor (GM-CSF)
      production utilizing different cell populations from three distinct murine
      stains. FK 565 produced an increase in GM-CSF release in all three experimental
      models used, providing evidence that FK 565 is among other things, a macrophage
      stimulating agent. Bleomycin increased GM-CSF release in the BALB/c and the
      'Scid' mouse. Paradoxically with cells from the 'nude' mouse a significant
      decrease was observed, indicating that Bleomycin may induce a suppressive effect
      on B-cells. Cyclosporin A was found to inhibit the release of GM-CSF from BALB/c
      mice, however, no effect was observed in either 'nude' or 'Scid' mice.

PMID- 7504661
TI  - Efficacy of anti-CD5 F(ab')2 and Fab' immunoconjugates in human peripheral blood
      lymphocyte-reconstituted severe combined immunodeficient mice.
AB  - A human peripheral blood lymphocyte-reconstituted severe combined immunodeficient
      (hu-PBL-SCID) mouse model was used to compare in vivo efficacy of
      immunoconjugates directed against the CD5 antigen present on human T-cells. Four
      anti-CD5 immunoconjugates were tested, composed of chimeric human-mouse (cH65)
      F(ab')2 or Fab' fragments chemically linked to recombinant gelonin (rGEL) or the
      30,000 M(r) glycoform of ricin A chain (RTA30). Immunoconjugate treatment was
      initiated approximately 3 weeks after PBL transplantation and consisted of five
      consecutive daily bolus i.v. injections. Efficacy was subsequently assessed by
      quantitation of human T-cells in spleens, blood and peritoneal lavage fluid using
      3-color flow cytometry. cH65 F(ab')2- and cH65 Fab'-rGEL conjugates were
      essentially equally effective at depleting human T-cells from SCID mouse tissues,
      suggesting that bivalent binding is not required for efficacy when rGEL is the
      cytotoxic moiety. Treatment with unconjugated F(ab')2, unconjugated Fab' or a Fab
      rGEL immunoconjugate of irrelevant binding specificity did not result in a
      significant depletion of T-cells, demonstrating that the cytotoxic moiety and a
      relevant human T-cell binding moiety are both required for efficacy. In contrast
      to the results observed with the rGEL conjugates, cH65 Fab'-RTA30 was not as
      effective as cH65 F(ab')2-RTA30 in depleting human T-cells from SCID mouse
      tissues. This paralleled in vitro findings in a human PBMC cytotoxicity assay,
      which demonstrated that cH65 Fab'-RTA30 was 17-fold less potent than cH65 F(ab')2
      RTA30 and approximately 50-fold less potent than the rGEL conjugates.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7504662
TI  - Association of Ulex europaeus agglutinin I binding with invasion in endometrial
      carcinoma.
AB  - Ulex europaeus agglutinin I (UEA-I), a lectin which specifically binds L-fucose,
      has been shown to extensively bind endometrial carcinoma cells but not benign
      endometrial glands. Patterns of UEA-I binding were examined in five cases of
      uteri containing proliferative endometrium, five cases of endometrial
      hyperplasia, and 54 cases of endometrioid (typical) carcinoma of the endometrium
      and correlated with the histologic features of the tumor and its behavior.
      Whereas proliferative endometrium showed luminal staining only, diffuse
      cytoplasmic staining was frequently seen in hyperplasia and carcinoma. Carcinomas
      with a high percentage of tumor cells staining with UEA-I tended to be high-grade
      with a greater tendency to deep myometrial and vascular invasion than tumors with
      little or no staining. By univariate survival analysis, the extent of UEA-I
      binding was found to correlate with patient survival. By multivariate analysis,
      however, survival correlated most closely with the presence of deep myometrial
      and vascular invasion, and UEA-I binding was not found to be an independent
      prognostic indicator. This study suggests that increased fucosylation of proteins
      in endometrioid cancer cells may play a role in myometrial and vascular invasion.

PMID- 7504663
TI  - Ultrastructure and chemical composition of the sheath of Leptothrix discophora SP
      6.
AB  - Light microscopy and transmission electron microscopy of thin sections and metal
      shadowed specimens showed that the sheath of Leptothrix discophora SP-6 (ATCC
      51168) is a tube-like extracellular polymeric structure consisting of a condensed
      fabric of 6.5-nm-diameter fibrils underlying a more diffuse outer capsular layer.
      In thin sections, outer membrane bridges seen to contact the inner sheath layer
      suggested that the sheath fabric was attached to the outer layer of the gram
      negative cell wall. The capsular polymers showed an affinity for cationic
      colloidal iron and polycationic ferritin, indicating that they carry a negative
      charge. Cell-free sheaths were isolated by treatment with a mixture of lysozyme,
      EDTA, and N-lauroylsarcosine (Sarkosyl) or sodium dodecyl sulfate (SDS). Both
      Sarkosyl- and SDS-isolated sheaths were indistinguishable in microscopic
      appearance. However, the Mn-oxidizing activity of Sarkosyl-isolated sheaths was
      more stable than that of SDS-isolated sheaths. The Sarkosyl-isolated sheaths also
      contained more 2-keto-3-deoxyoctanoic acid and more outer membrane protein than
      SDS-isolated sheaths. The oven-dried mass of detergent-isolated sheaths
      represented approximately 9% of the total oven-dried biomass of SP-6 cultures;
      the oven-dried sheaths contained 38% C, 6.9% N, 6% H, and 2.1% S and
      approximately 34 to 35% carbohydrate (polysaccharide), 23 to 25% protein, 8%
      lipid, and 4% inorganic ash. Gas-liquid chromatography showed that the
      polysaccharide was an approximately 1:1 mixture of uronic acids (glucuronic,
      galacturonic, and mannuronic acids and at least one other unidentified uronic
      acid) and an amino sugar (galactosamine). Neutral sugars were not detected. Amino
      acid analysis showed that sheath proteins were enriched in cysteine (6 mol%). The
      cysteine residues in the sheath proteins probably provide sulfhydryls for
      disulfide bonds that play an important role in maintaining the structural
      integrity of the sheath (D. Emerson and W.C. Ghiorse, J. Bacteriol. 175:7819
      7827, 1993).

PMID- 7504665
TI  - The extracellular protein regulator (xpr) affects exoprotein and agr mRNA levels
      in Staphylococcus aureus.
AB  - xpr, a regulatory element of exoprotein synthesis in Staphylococcus aureus,
      defined by an insertion of Tn551 into the chromosome of strain S6C, affects the
      expression of several exoproteins at the mRNA level. Drastic reduction in
      transcript levels for staphylococcal enterotoxin B (seb), lipase (geh), alpha
      toxin (hla), and delta-toxin (hld) were detected, while mRNA levels for coagulase
      (coa) and protein A (spa) were elevated. Because the delta-toxin gene resides
      within the RNAIII transcript of the exoprotein regulator, agr, the reduction in
      hld message in the mutant strain of S6C is indicative of additional regulatory
      events in exoprotein gene expression. Northern (RNA) analysis of total cellular
      RNA hybridized with probes specific for RNAII and RNAIII (the two major
      transcripts of the agr operon) showed that both transcripts were reduced 16- to
      32-fold at 3 h (late exponential phase) and 8- to 16-fold at 12 h
      (postexponential phase). These data confirm our original findings (M. S.
      Smeltzer, M. E. Hart, and J. J. Iandolo, Infect. Immun. 61:919-925, 1993) that
      two regulatory loci, agr and xpr, are interactive at the genotypic level.

PMID- 7504666
TI  - Temperature sensing in Yersinia pestis: translation of the LcrF activator protein
      is thermally regulated.
AB  - The lcrF gene of Yersinia pestis encodes a transcription activator responsible
      for inducing expression of several virulence-related proteins in response to
      temperature. The mechanism of this thermoregulation was investigated. An lcrF
      clone was found to produce much lower levels of LcrF protein at 26 than at 37
      degrees C in Y. pestis, although it was transcribed at similar levels at both
      temperatures. High-level T7 polymerase-directed transcription of the lcrF gene in
      Escherichia coli also resulted in temperature-dependent production of the LcrF
      protein. Pulse-chase experiments showed that the LcrF protein was stable at 26
      and 37 degrees C, suggesting that translation rate or message degradation is
      thermally controlled. The lcrF mRNA appears to be highly unstable and could not
      be reliably detected in Y. pestis. Insertion of the lcrF gene into plasmid pET4a,
      which produces high levels of plasmid-length RNA, aided detection of lcrF
      specific message in E. coli. Comparison of the amount of LcrF protein produced
      per unit of message at 26 and 37 degrees C indicated that the efficiency of
      translation of lcrF message increased with temperature. mRNA secondary structure
      predictions suggest that the lcrF Shine-Dalgarno sequence is sequestered in a
      stem-loop. A model in which decreased stability of this stem-loop with increasing
      temperature leads to increased efficiency of translation initiation of lcrF
      message is presented.

PMID- 7504664
TI  - Salicylate induction of antibiotic resistance in Escherichia coli: activation of
      the mar operon and a mar-independent pathway.
AB  - Since the growth of wild-type Escherichia coli in salicylate results in a
      multiple antibiotic resistance phenotype similar to that of constitutive mutants
      (Mar) of the chromosomal mar locus, the effect of salicylate on the expression of
      the marRAB operon was investigated. The amount of RNA hybridizing with a mar
      specific DNA probe was 5 to 10 times higher in wild-type cells grown with sodium
      salicylate (5.0 mM) than in untreated controls. Untreated Mar mutants had three
      to five times more mar-specific RNA than wild-type cells did. When a Mar mutant
      was treated with salicylate, a 30- to 50-fold increase of mar-specific RNA was
      seen. In wild-type cells bearing a mar promoter-lacZ fusion on the chromosome,
      salicylate increased beta-galactosidase activity by sixfold. Thus, salicylate
      induces transcription of the marRAB operon. Other inducers of phenotypic multiple
      antibiotic resistance, e.g., benzoate, salicyl alcohol, and acetaminophen, but
      not acetate, also increased transcription from the mar promoter but to a lesser
      extent than did salicylate. Both in wild-type and mar-deficient strains, growth
      in salicylate resulted in increased antibiotic resistance, decreased permeation
      of the outer membrane to cephaloridine, increased micF transcription, and
      decreased amounts of OmpF. However, the magnitude of these changes was generally
      greater in wild-type (mar-containing) cells. Thus, salicylate and other compounds
      can induce transcription of the mar operon and, presumably, give rise to multiple
      antibiotic resistance via this pathway. However, salicylate can also activate an
      unidentified, mar-independent pathway(s) which engenders multiple antibiotic
      resistance.

PMID- 7504667
TI  - Transcriptional regulation of the Bacillus thuringiensis subsp. thompsoni crystal
      protein gene operon.
AB  - The two predominant polypeptides of the Bacillus thuringiensis subsp. thompsoni
      crystal are encoded by the cry40 and cry34 genes. These crystal protein genes are
      located in an operon. Western analysis (immunoblotting) demonstrated that the
      operon promoter activity was located in the region upstream of the cry40 gene.
      The Cry34 protein was expressed only when the upstream promoter region was
      present. The crystal protein genes are the only cistrons in the operon, and they
      are expressed during sporulation, with the highest transcript levels detected
      early in sporulation (1.5 to 3 h after the onset of sporulation). Transcription
      initiates from two adjacent sites located 84 and 85 bases upstream of the cry40
      translational start codon. The B. thuringiensis subsp. thompsoni crystal protein
      gene operon promoter aligned with other crystal protein gene promoters, which are
      activated from early to midsporulation and transcribed in vitro by the B.
      thuringiensis RNA polymerase E sigma 35.

PMID- 7504670
TI  - Evaluating biomedical media services.
AB  - Rising service costs, increasing demands, user dissatisfaction, and new
      technology applications for biomedical media services prompted Loyola University
      of Chicago Medical Center to review how such services are provided and utilized
      at the medical center. Several activities conducted to investigate five
      biomedical media services operational concerns are summarized. Discussion
      includes seven developmental stages of biomedical media services, a nine-step
      planning process, and recommendations for a centrally administered service unit.

PMID- 7504669
TI  - Differential decay of RNA of the CFA/I fimbrial operon and control of relative
      gene expression.
AB  - CFA/I fimbriae on human enterotoxigenic Escherichia coli are composed of the CfaB
      protein, the product of the second gene of the CFA/I operon. We show here that
      CfaB is expressed at a higher level than other proteins of the CFA/I operon. mRNA
      encoding the CfaB protein is much more abundant than mRNA encoding CfaA, the
      first protein, together with CfaB or mRNA encoding CfaA only. Only one promoter,
      upstream of cfaA, is present. These data indicate that a primary transcript
      containing cfaA and cfaB is processed into a cfaA-specific mRNA and a cfaB
      specific mRNA. The cfaA mRNA is unstable, while the cfaB mRNA is stable and
      therefore accumulates in CFA/I-producing E. coli. The cfaB mRNA is probably
      stabilized by a stem-loop structure downstream of the cfaB gene. No distinct mRNA
      fragments could be detected encoding the other two proteins, CfaC and CfaE, of
      the CFA/I operon. These results indicate that cfaC- and cfaE-specific mRNAs
      degrade very rapidly and/or are produced in small amounts.

PMID- 7504668
TI  - Transcriptional analysis of the Aeromonas salmonicida S-layer protein gene vapA.
AB  - The vapA gene of Aeromonas salmonicida encodes the subunit of the surface protein
      array known as A-layer. Nucleotide sequence analysis of the 374 bp of DNA
      immediately upstream of vapA revealed two potential promoter sequences and other
      possible regulatory sequences. Sequencing and polymerase chain reaction analysis
      showed that the region was conserved in wild-type A. salmonicida. Primer
      extension and Northern (RNA) blot analysis showed that vapA transcription in A.
      salmonicida was directed predominantly by a distal promoter, P1, resulting in a
      1.7-kb unit-length mRNA with an untranslated 181-nucleotide leader sequence which
      contained two predicted low-free-energy stem-loop structures. Northern analysis
      of cells grown at 15 degrees C showed that vapA transcript production peaked
      during the mid-log phase of growth (A600 = 0.25). At 15 degrees C, the half-life
      of the vapA mRNA was 22 min, while at 20 degrees C, the half-life was
      significantly shorter, 11 min. The amount of vapA transcript produced was reduced
      by growth in the presence of the DNA gyrase inhibitors nalidixic acid and
      novobiocin. Environmental factors such as growth temperature and atmospheric
      oxygen tension also affected the quantity of vapA mRNA. vapA transcript could not
      be detected in mutants which produced either low levels of full-length or
      truncated A protein or no detectable A protein.

PMID- 7504671
TI  - Demonstration of receptors for insulin-like growth factor binding protein-3 on
      Hs578T human breast cancer cells.
AB  - Hs578T human breast cancer cells are from an estrogen receptor-negative breast
      cell line derived from a highly aggressive mammary tumor. Our previous insulin
      like growth factor binding protein-3 (IGFBP-3) binding studies (Oh, Y., Muller,
      H. L., Lamson, G., and Rosenfeld, R. G. (1993) J. Biol. Chem. 268, 14964-14971)
      have demonstrated specific binding of IGFBP-3 on the Hs578T cell surface and a
      significant inhibitory effect of IGFBP-3, itself, on monolayer growth. In this
      study, we have demonstrated cell surface association proteins that are specific
      for IGFBP-3 by showing: 1) detection of 20-, 26-, and 50-kDa proteins by affinity
      cross-linking with 125I-IGFBP-3E. coli and immunoprecipitation of cell monolayers
      and cell lysates with anti-IGFBP-3 antibodies; 2) dose-dependent competition of
      125I-IGFBP-3E. coli by unlabeled IGFBP-3E. coli; 3) inhibition of IGFBP-3 binding
      to these cell surface proteins by EDTA and by coincubation with native insulin
      like growth factor II (IGF-II), but not by coincubation with
      [Gln6,Ala7,Tyr18,Leu19,Leu27]IGF-II, an IGF-II analog with decreased affinity for
      IGFBP-3; and 4) partial purification of 20- and 26-kDa species by IGFBP-3.anti
      IGFBP-3 antibody immunoaffinity membranes. Characteristics of these specific
      IGFBP-3 cell surface association proteins are identical to those observed in our
      previous monolayer binding assay and monolayer growth assay experiments. The
      specificity of binding and the inhibitory effect of IGFBP-3 binding on Hs578T
      cell growth suggest that these cell surface proteins are IGFBP-3-specific
      receptors or receptor subunits mediating the direct inhibitory effect of IGFBP-3
      on monolayer growth of Hs578T cells.

PMID- 7504672
TI  - Functional characterization of beta isoforms of murine Na,K-ATPase. The adhesion
      molecule on glia (AMOG/beta 2), but not beta 1, promotes neurite outgrowth.
AB  - We have previously provided evidence for a dual function of the adhesion molecule
      on glia (AMOG/beta 2), the beta 2 subunit of the murine Na,K-ATPase, both as
      neural recognition molecule mediating neuron-glia interactions and as functional
      beta subunit of the sodium pump. To analyze the functional role of AMOG/beta 2 in
      neurite outgrowth, AMOG/beta 2-expressing L-cells were generated by transfection
      and used as substrates for neurite outgrowth of cerebellar and hippocampal
      neurons. AMOG/beta 2-transfected L-cells led to an increase in neurite length
      after 6 h, which was specifically inhibited by antibodies to AMOG/beta 2 and a
      neuronal membrane fraction. Moreover, the extracellular domain of AMOG/beta 2
      generated as a soluble recombinant protein in Chinese hamster ovary cells
      partially inhibited the increase in neurite outgrowth on AMOG/beta 2-transfected
      L-cells. L-cells transfected with the mouse beta 1 subunit had no effect on
      neurite extension. Our observations show for the first time differences in
      functional properties for different beta isoforms of the Na,K-ATPase and suggest
      that AMOG/beta 2 but not beta 1 is able to interact with an unknown neuronal
      receptor leading to increased neurite outgrowth, most likely via signal
      transduction.

PMID- 7504673
TI  - Amyloid-like properties of peptides flanking the epitope of amyloid precursor
      protein-specific monoclonal antibody 22C11.
AB  - Alzheimer's disease is one of the prevalent forms of human dementia. Its
      pathology is distinguished by proteinaceous deposits ("amyloid") in the brain.
      They contain a peptide (beta A4) that is proteolytically derived from a larger
      transmembrane protein. To follow the different metabolic pathways of this Amyloid
      Precursor Protein (APP) may thus lead to the elucidation of the molecular basis
      of Alzheimer's disease. Specific antibodies are necessary tools for this task.
      Using synthetic peptides, we have characterized the epitope of the APP-specific
      monoclonal antibody 22C11; it is localized between residues 66 and 81 of APP.
      Some of the peptides flanking this site exhibited properties generally associated
      with amyloid, i.e. low solubility, filament formation, and birefringence after
      Congo Red staining. Exploiting differences in the peptides' aggregational
      properties, we present evidence that the two dyes Eosin and Direct Red 254, in
      conjunction with classical amyloid staining by Congo Red, can be used to
      characterize aggregating, amyloid-like peptides in vitro.

PMID- 7504674
TI  - A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of the
      inter alpha-trypsin inhibitor.
AB  - We showed previously that hyaluronan (HA) synthesized by cultured fibroblasts
      firmly bound 85-kDa proteins. The proteins were derived from serum used for the
      culture and appeared to be covalently linked to HA (Yoneda, M., Suzuki, S., and
      Kimata, K. (1990) J. Biol. Chem. 265, 5247-5257). In these regards, we named this
      molecule SHAP (serum-derived HA associated proteins). Incubation of serum with
      exogenous HA under physiological conditions enabled us to prepare SHAP.HA complex
      without cell cultivation. The complex thus obtained from bovine or human serum
      was served for the characterization of SHAP. Digestion with HA-lyase and
      subsequent separation on SDS-polyacrylamide gel electrophoresis yielded two
      components, X and Y. Because of the block of their NH2 termini, peptides were
      obtained by the digestion of X and Y with V8 protease, separated on SDS-polyacryl
      amide gel electrophoresis and then subjected to the analysis. Peptides from X and
      Y showed a high degree of sequence similarity to the two heavy chains, HC2 and
      HC1, of human inter-alpha-trypsin inhibitor (ITI), respectively (over 80% with
      bovine SHAP and essentially 100% with human SHAP). Cross-reactivity with
      antibodies against ITI supported the findings. Direct digestion of the complex
      with V8 protease and the subsequent purification of the HA-resistant fragment
      complex were performed to identify the HA-binding domains. NH2-terminal sequences
      of the fragments suggested the participation of the COOH-terminal half of ITI
      with an amphipathic alpha helix structure in the HA binding.

PMID- 7504675
TI  - The 47-kD lens-specific protein phakinin is a tailless intermediate filament
      protein and an assembly partner of filensin.
AB  - In previous studies we have characterized a lens-specific intermediate filament
      (IF) protein, termed filensin. Filensin does not self-assemble into regular IFs
      but is known to associate with another 47-kD lens-specific protein which has been
      suggested to represent its assembly partner. To address this possibility, we
      cloned and sequenced the cDNA coding for the bovine 47-kD protein which we have
      termed phakinin (from the greek phi alpha kappa omicron sigma = phakos = lens).
      The predicted sequence comprises 406 amino acids and shows significant similarity
      (31.3% identity over 358 residues) to type I cytokeratins. Phakinin possesses a
      95-residue, non-helical domain (head) and a 311 amino acid long alpha-helical
      domain punctuated with heptad repeats (rod). Similar to cytokeratin 19, phakinin
      lacks a COOH-terminal tail domain and it therefore represents the second known
      example of a naturally tailless IF protein. Confocal microscopy on frozen lens
      sections reveals that phakinin colocalizes with filensin and is distributed along
      the periphery of the lens fiber cells. Quantitative immunoblotting with whole
      lens fiber cell preparations and fractions of washed lens membranes suggest that
      the natural stoichiometry of phakinin to filensin is approximately 3:1. Under in
      vitro conditions, phakinin self-assembles into metastable filamentous structures
      which tend to aggregate into thick bundles. However, mixing of phakinin and
      filensin at an optimal ratio of 3:1 yields stable 10-nm filaments which have a
      smooth surface and are ultrastructurally indistinguishable from "mainstream" IFs.
      Immunolabeling with specific antibodies shows that these filaments represent
      phakinin/filensin heteropolymers. Despite its homology to the cytokeratins,
      phakinin does not coassemble with acidic (type I), or basic (type II)
      cytokeratins. From these data we conclude that filensin and phakinin are obligate
      heteropolymers which constitute a new membrane-associated, lens-specific filament
      system related to, but distinct from the known classes of IFs.

PMID- 7504676
TI  - Beta 2 integrin engagement triggers actin polymerization and phosphatidylinositol
      trisphosphate formation in non-adherent human neutrophils.
AB  - Beta 2 integrins are involved in the adhesion of leukocytes to other cells and
      surfaces. Although adhesion is required for cell locomotion, little is known
      regarding the way beta 2 integrin-receptors affect the actin network in
      leukocytes. In the present study filamentous actin (F-actin) levels in non
      adherent human neutrophils have been measured by phalloidin staining after
      antibody cross-linking of beta 2 integrins. Antibody engagement of beta 2
      integrins resulted in a rapid and sustained (146 and 131% after 30 and 300 s,
      respectively) increase in the neutrophil F-actin content. This is in contrast to
      stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), which
      causes a prompt and pronounced but rapidly declining rise in F-actin (214 and
      127% after 15 and 300 s, respectively). Priming neutrophils with 1 nM PMA, a low
      concentration that did not influence the F-actin content per se, increased the
      magnitude of the beta 2 integrin-induced response but had no effect on the
      kinetics (199% after 30 s and 169% after 300 s). Removal of extracellular Ca2+
      only marginally affected the beta 2 integrin-induced F-actin response for cells
      that were pretreated with PMA whereas the response for nonprimed cells was
      reduced by half. This suggests that even though extracellular Ca2+ has a
      modulatory effect it is not an absolute requirement for beta 2 integrin-induced
      actin polymerization. beta 2 integrin engagement did not affect the resting
      cellular level of cAMP arguing against a role of cAMP in beta 2 integrin-induced
      actin assembly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504678
TI  - Lineage commitment in human hemopoiesis involves asymmetric cell division of
      multipotent progenitors and does not appear to be influenced by cytokines.
AB  - Different models have been proposed to explain lineage commitment in hemopoiesis.
      Some suggest that lineage commitment occurs in a stochastic manner without the
      direct influence of extracellular factors; others postulate that cytokines
      determine whether multipotent cells will become erythroid or
      granulocyte/macrophage progenitors. In the present study, the patterns of
      proliferation and differentiation of individually sorted human cord blood-derived
      primitive hemopoietic cells (highly enriched for multipotent progenitors) were
      analyzed in a serum-free culture system supplemented with different cytokine
      combinations. In a first set of experiments, the response of individual cells to
      different cytokine combinations was compared, whereas in a second set of
      experiments, single cells were allowed to undergo one division after which the
      two daughter cells were physically separated and cultured in either the same or
      different cytokine combinations. Proliferation of progenitor cells was absolutely
      dependent on cytokines, and the combination of mast cell growth factor plus
      interleukin 6 was sufficient to induce mitosis. When cytokine combinations
      favoring erythropoiesis and/or myelopoiesis were added to the cultures, a more
      vigorous proliferative response of the sorted primitive progenitors was observed.
      Interestingly, the relative proportions of granulocyte/macrophage, erythroid, and
      multipotent progenitors remained more or less the same regardless of the cytokine
      combination used, indicating a permissive rather than an instructive role for
      cytokines in hemopoietic differentiation. Asymmetric cell divisions, defined as a
      division that yields two daughter cells with distinct functional properties, were
      observed in 3-17% of the progenitor cells capable of forming colonies under our
      experimental conditions. In the rest, symmetric divisions involving multipotent
      and lineage-committed progenitors were observed. The results of this study
      demonstrate that the asymmetric cell divisions that occur in the early stages of
      hemopoiesis at the level of multipotent progenitors cannot be skewed by the
      addition of specific cytokine combinations. These findings support the hypothesis
      that lineage commitment in hemopoiesis occurs in a stochastic manner by
      mechanisms that remain to be elucidated.

PMID- 7504677
TI  - Targeted deletion of beta 1 integrins in F9 embryonal carcinoma cells affects
      morphological differentiation but not tissue-specific gene expression.
AB  - The integrin superfamily of heterodimeric transmembrane adhesion receptors
      mediates many cell-cell and cell-matrix interactions whose functions are believed
      to be critical for normal morphogenesis and differentiation. By eliminating the
      beta 1 integrin gene through homologous recombination, we have assessed the role
      of the beta 1 integrin family in the F9 embryonal carcinoma model for endodermal
      differentiation. F9 cells were unexpectedly found to maintain three copies of the
      beta 1 gene and complete elimination required three sequential rounds of
      targeting to generate triple knockout lines (beta 1 TKO). Elimination of the beta
      1 integrin family of adhesion receptors from F9 cells resulted in reduced
      adhesion to fibronectin, laminin and collagen, but strongly enhanced adhesion to
      vitronectin. The absence of beta 1 integrins did not promote significant
      compensatory upregulation of either beta 3 or beta 5 subunits, both of which are
      known to act as vitronectin receptors when associated with alpha v. The loss of
      beta 1 integrins severely affected morphological differentiation when the beta 1
      deficient cells were induced to differentiate to either parietal or visceral
      endoderm. Parietal endoderm derived from beta 1-deficient cells retained a
      rounded morphology and migrated poorly on both fibronectin and vitronectin.
      Visceral endoderm derived from beta 1-deficient cells were also unable to form a
      normal, confluent epithelial monolayer; instead, a non-contiguous layer
      containing clumps of disorganized cells was observed. However, loss of beta 1
      integrins did not interfere with induction by differentiating agents of tissue
      specific gene products for either visceral or parietal endoderm. These results
      suggest that beta 1 integrins mediate morphological differentiation (migration
      and epithelial formation) but not tissue-specific gene expression in induced F9
      cells, and that these two processes are not necessarily linked in this system.

PMID- 7504679
TI  - Effect of stretch on growth and collagen synthesis in cultured rat and lamb
      pulmonary arterial smooth muscle cells.
AB  - There are no studies of the effect of stretch in cultured pulmonary vascular
      smooth muscle, and some data suggest that a stretch-mediated increase in
      connective tissue synthesis in pulmonary arteries is mediated by the endothelium.
      To investigate whether stretch can serve as a growth stimulus in this smooth
      muscle, we studied two types of cultured pulmonary arterial smooth muscle cells
      (a multiply passaged clonal line of rat cells [PAC1], and early passage lamb
      cells [EPTC]). Cells were grown on a collagen-coated silicone surface and
      subjected to repetitive stretch (0.33-0.5 Hz; 10-20% strain). The relative rates
      of total RNA, DNA, protein, and soluble collagen synthesis were determined using
      3H precursors, and c-fos and collagen mRNAs by Northern blot analysis. Stretch
      caused no significant change in the rate of RNA synthesis in either PAC1 cells
      (+9%) or EPTC (-3%). The relative rate of total protein synthesis was decreased
      by stretch (6% in PAC1 cells and 36% in EPTC [both NS]) as was the rate of
      collagen synthesis (-24% in EPTC [NS]). In EPTC, the percentage of 3H-thymidine
      labeled cells was modestly increased with 24 h stretch (17 +/- 5.7%; P < .001),
      but trichloroacetic acid (TCA) precipitated 3H-thymidine was unaltered by
      stretch, and the number of cells not significantly changed with stretch. c-fos
      mRNA expression was only inconsistently induced by stretch x 30 min in EPTC, and
      not at all in PAC1 cells. Expression of mRNA for alpha 1 (I) and alpha 1 (III)
      collagen was not changed significantly by 24 h or 48 h of stretch. We conclude
      that stretch does not serve as a significant growth stimulus in cultured
      pulmonary vascular smooth muscle cells in this system. These findings do not rule
      out the possibility that stretch is a growth stimulus for these cells under
      different conditions, but do suggest that other models will be needed to
      determine if and how mechanical stimuli affect growth of pulmonary vascular
      smooth muscle.

PMID- 7504680
TI  - Automation of protein 2D proton NMR assignment by means of fuzzy mathematics and
      graph theory.
AB  - The novel methodology for protein 2D NMR assignment presented in this paper is
      based upon protein spin coupling graph theory analysis, fuzzy graph pattern
      recognition, and tree searching. The method required to formalize the whole
      assignment procedure into a logical system which can be properly processed by
      computer software is also discussed. Solutions for peak overlaps, spin coupling
      network overlaps, and details related to the automated assignment of BPTI are
      reported as well.

PMID- 7504681
TI  - [Cytokine response to surgical stress].

PMID- 7504682
TI  - Corpus luteum failure in ectopic pregnancy.
AB  - The endocrinology of ectopic pregnancy was studied in order to investigate the
      origin of the discordance in the circulating amounts of human chorionic
      gonadotrophin (HCG) and those of oestradiol and progesterone. Serial maternal
      blood samples were obtained at 4-9 weeks gestation from 93 patients who became
      pregnant following in-vitro fertilization and embryo transfer including 10
      ectopic, 21 anembryonic and 62 normal singleton pregnancies. The samples were
      analysed for HCG, Schwangerschaft protein-1 (SP-1), pregnancy-associated plasma
      protein-A (PAPP-A), progesterone and oestradiol. In ectopic pregnancies,
      concentrations of all substances analysed were significantly reduced compared to
      singleton pregnancies from 5 weeks gestation (P < 0.05-0.001) but they were not
      significantly different from those of anembryonic pregnancies. In ectopic
      pregnancies, associations were found between the concentration of both HCG and SP
      1 and those of progesterone and oestradiol. No associations were found between
      PAPP-A and any other substances analysed. This may be due to insensitivity of the
      PAPP-A assay; alternatively PAPP-A concentrations may be differentially reduced
      in ectopic pregnancy. These findings suggest that progesterone and oestradiol are
      derived from the corpus luteum in early ectopic pregnancy but that the corpus
      luteum fails rapidly and the dominant source of both hormones becomes the
      trophoblast as early as 5 weeks.

PMID- 7504683
TI  - Interactions between the embryo and corpus luteum.
AB  - A total of 102 patients who had become pregnant following in-vitro fertilization
      (IVF) and embryo transfer were studied at weekly intervals between 4 and 14 weeks
      gestation. The pregnancies were classified as follows: (i) normal singleton, n =
      52; (ii) normal twin, n = 24; (iii) heterotopic, n = 4 (weeks 4-8 only); and (iv)
      anembryonic with a viable intra-uterine singleton, n = 22. The serum
      concentrations of human chorionic gonadotrophin (hCG), Schwangerschaft protein-1
      (SP-1) and pregnancy-associated plasma protein-A (PAPP-A), oestradiol and
      progesterone were measured. The mean serum concentrations of HCG, SP-1 and PAPP-A
      were significantly less in heterotopic than in singleton, singleton/anembryonic
      or twin pregnancies (P < 0.01-0.05), while those of progesterone and oestradiol
      were not different at any time. There were no significant differences between the
      serum concentrations of any of the substances analysed in singleton/anembryonic
      and singleton pregnancies, but the concentrations of all the substances analysed
      were significantly greater in twin pregnancies from as early as 7 weeks (P < 0.01
      0.05). These data show that in heterotopic pregnancies trophoblast function is
      reduced, as suggested by the lower concentrations of the placental proteins.
      Despite this the concentrations of oestradiol and progesterone, derived
      predominantly from the corpus luteum between 4 and 8 weeks, are equivalent to
      those found in twin pregnancies, and greater than those found in singleton and
      singleton/anembryonic pregnancies. These findings support the notion that
      although HCG may rescue the corpus luteum it does not subsequently have a direct
      effect on its function, and suggest that the embryo may influence corpus luteum
      function.

PMID- 7504684
TI  - Arbitrarily primed polymerase chain reaction as a rapid method to differentiate
      crossed from independent Pseudomonas cepacia infections in cystic fibrosis
      patients.
AB  - We used DNA fingerprinting by the arbitrarily primed polymerase chain reaction
      (AP-PCR) technique for an epidemiological investigation of 23 Pseudomonas cepacia
      isolates obtained from 11 cystic fibrosis (CF) patients attending our CF center.
      This approach was compared with ribotyping, pulsed-field gel electrophoresis
      (PFGE), and conventional phenotypic typing. AP-PCR and ribotyping were identical
      in resolving power, since the two methods generated four different profiles and
      identified the same group of strains. Six patients on the one hand and four on
      the other harbored strains of the same genotype, thus raising the possibility of
      either patient-to-patient transmission or acquisition from a common hospital
      environmental source. PFGE results were in good agreement with those of the other
      two methods, but PFGE seems more discriminative since it generated a fifth
      profile for a single strain in a group of four. Our results show in vivo
      stability for the three methods during a period extending from 3 to 41 months.
      These genotypic techniques are particularly promising for clinical laboratories
      to help to clarify the epidemiology of P. cepacia in CF patients. The AP-PCR
      method constitutes an easier alternative to the well-established ribotyping
      method. AP-PCR provides the quickest results with minimal technical complexity.
      However, our results suggest that it is less discriminative than the labor
      intensive PFGE method.

PMID- 7504685
TI  - Isolation and characterization of "Flexispira rappini" from laboratory mice.
AB  - A bacterium with an unusual ultrastructure and possessing a fusiform protoplasmic
      cylinder, spiral periplasmic fibers, and bipolar tufts of sheathed flagella was
      identified in the intestinal mucosae of laboratory mice. The organism was
      cultured under microaerophilic conditions and was found to rapidly hydrolyze
      urea. On the basis of 16S rRNA gene sequence analysis, the organism was shown to
      be "Flexispira rappini." "F. rappini" is closely related to members of the genus
      Helicobacter and has been reported to be associated with human gastroenteritis
      and ovine abortion. "F. rappini" has not previously been observed in the
      gastrointestinal tracts of mice.

PMID- 7504686
TI  - Cultivation of cilia-associated respiratory bacillus in artificial medium and
      determination of the 16S rRNA gene sequence.
AB  - Cilia-associated respiratory (CAR) bacillus, an unclassified gliding bacterium
      associated with respiratory disease in rats, mice, and rabbits, has previously
      been cultivated only in embryonated chicken eggs, cell culture, or cell culture
      medium supplemented with conditioned medium from cultured tracheas. A reference
      strain of CAR bacillus, originally isolated in eggs, grew in cell culture flasks
      as adherent individual bacilli and ropy, whorled fascicles in cell culture media
      supplemented only with fetal calf serum. Using Dulbecco's minimal essential
      medium, we isolated CAR bacillus from naturally infected rats and a naturally
      infected rabbit and from experimentally inoculated mice and rats. Isolates were
      maintained for up to 20 passages. Isolates from rats were similar in morphology
      to the reference strain, but most were more actively motile and formed pincushion
      like aggregates. The rabbit bacilli were smaller and formed fewer aggregates.
      DNAs of rat isolates differed only slightly in restriction fragment patterns from
      that of the reference strain, whereas that of the rabbit isolate was distinctly
      different. Cultures of CAR bacilli of all strains from rats contained Mycoplasma
      fermentans, Mycoplasma pulmonis, or both, and cultures of the CAR bacillus from
      the rabbit contained an unidentified arginine-utilizing mycoplasma. The sequence
      of the 16S rRNA gene of the reference strain was determined by amplification by
      polymerase chain reaction, cloning of the product, and sequencing by the
      dideoxynucleotide chain termination method. Comparison of the sequence with
      sequences in the GenBank data base indicated that CAR bacillus is a unique
      organism most closely related to Flavobacterium ferrugineum and Flexibacter
      sancti.

PMID- 7504687
TI  - Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell
      tumorigenicity and increase mouse spleen natural killer cell activity.
      Implications for a possible role of tumor cell/host TGF-beta interactions in
      human breast cancer progression.
AB  - TGF-beta effects on angiogenesis, stroma formation, and immune function suggest
      its possible involvement in tumor progression. This hypothesis was tested using
      the 2G7 IgG2b, which neutralizes TGF-beta 1, -beta 2, and -beta 3, and the MDA
      231 human breast cancer cell line. Inoculation of these cells in athymic mice
      decreases mouse spleen natural killer (NK) cell activity. Intraperitoneal
      injections of 2G7 starting 1 d after intraperitoneal inoculation of tumor cells
      suppressed intraabdominal tumor and lung metastases, whereas the nonneutralizing
      anti-TGF-beta 12H5 IgG2a had no effect. 2G7 transiently inhibited growth of
      established MDA-231 subcutaneous tumors. Histologically, both 2G7-treated and
      control tumors were identical. Intraperitoneal administration of 2G7 resulted in
      a marked increase in mouse spleen NK cell activity. 2G7 did not inhibit MDA-231
      primary tumor or metastases formation, nor did it stimulate NK cell-mediated
      cytotoxicity in beige NK-deficient nude mice. Finally, serum-free conditioned
      medium from MDA-231 cells inhibited the NK cell activity of human blood
      lymphocytes. This inhibition was blocked by the neutralizing anti-TGF-beta 2G7
      antibody but not by a nonspecific IgG2. These data support a possible role for
      tumor cell TGF-beta in the progression of mammary carcinomas by suppressing host
      immune surveillance.

PMID- 7504688
TI  - Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes
      respond predominantly to myelin oligodendrocyte glycoprotein.
AB  - Although T cell responses to the quantitatively major myelin proteins, myelin
      basic protein (MBP) and proteolipid protein (PLP), are likely to be of importance
      in the course of multiple sclerosis (MS), cell-mediated autoimmune responses to
      other myelin antigens, in particular quantitatively minor myelin antigens, such
      as myelin-associated glycoprotein (MAG) and the central nervous system-specific
      myelin oligodendrocyte glycoprotein (MOG), could also play a prevalent role in
      disease initiation or progression. Highly purified myelin antigens were used in
      this study to assess cell-mediated immune response to MOG in MS patients, in the
      context of the reactivity to other myelin antigens, MBP, PLP, and MAG. The
      greatest incidence of proliferative response by MS peripheral blood lymphocytes
      was to MOG, as 12 of 24 patients tested reacted and, of these, 8 reacted to MOG
      exclusively. In contrast, only 1 control individual of 16 tested reacted
      positively to MOG. The incidence of responses to MBP, PLP, and MAG did not differ
      greatly between MS patients and control individuals. A predominant T cell
      reactivity to MOG in MS suggests an important role for cell-mediated immune
      response to this antigen in the pathogenesis of MS.

PMID- 7504689
TI  - Vitreous levels of the insulin-like growth factors I and II, and the insulin-like
      growth factor binding proteins 2 and 3, increase in neovascular eye disease.
      Studies in nondiabetic and diabetic subjects.
AB  - Retinal capillary nonperfusion results in neovascularization of the eye, which is
      restricted to the retina in less severe cases and progresses to the anterior
      chamber and the iris angle in the most advanced case, called rubeosis. This
      angioneogenesis may be induced by the release of retinal growth factors into the
      vitreous. This study compared levels of the IGF-I and IGF-II, and of the IGF
      binding protein-2 (IGFBP-2) and IGFBP-3 in vitreous from three groups with
      different degrees of retinal ischemia, as judged by the extent of
      neovascularization: a control group without new vessel formation, retinal
      neovascularization in patients with proliferative diabetic retinopathy, and
      massive ischemia of various causes resulting in rubeosis. IGF-I and IGFBP-3 were
      increased 10- and 13-fold in rubeosis (P << 0.01) compared with no ischemia (n =
      10), while IGF-II and IGFBP-2 were elevated 2.7- and 4.3-fold (P < 0.01). Within
      the rubeosis group similar changes were observed independently of the cause of
      ischemia, which was central vein occlusion, ischemic ophthalmopathy, or
      intraocular tumor in seven cases and diabetic retinopathy in three samples from
      two patients. Vitreous from patients with proliferative diabetic retinopathy but
      without rubeosis (n = 16) contained 2.5- and 2.2-fold elevated levels of IGF-I
      and of IGFBP-2 (P < 0.05), while IGF-II and IGFBP-3 were increased 1.4- and 1.6
      fold, which was not significant. We conclude that: (a) ischemia appears to be a
      strong stimulus for the local production of IGF-I and -II and of IGFBP-2 and -3
      in the eye. (b) Changes in IGF-I and IGFBP-2 in proliferative diabetic
      retinopathy may be secondary to local ischemia rather than being specific for
      diabetic retinopathy. (c) IGF-I and IGFBP-3 may play a role in mediating
      angioneogenesis in the eye.

PMID- 7504690
TI  - Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis.
      Complexity of the response and dominance of nested epitopes due to recruitment of
      multiple T cell clones.
AB  - The human T cell response to the myelin basic protein (MBP) has been studied with
      respect to T cell receptor (TCR) usage, HLA class II restriction elements, and
      epitope specificity using a total of 215 long-term MBP-specific T cell lines
      (TCL) isolated from the peripheral blood of 13 patients with multiple sclerosis
      (MS) and 10 healthy donors. In most donors, the anti-MBP response was exceedingly
      heterogeneous. Using a panel of overlapping synthetic peptides spanning the
      entire length of human MBP, at least 26 epitopes recognized by human TCL could be
      distinguished. The MBP domain most commonly recognized was sequence 80-105 (31%
      of MS TCL, and 24% of control TCL). Sequence 29-48 was recognized more frequently
      by control-derived TCL (24%) than by TCL from MS patients (5%). The MBP epitopes
      were recognized in the context of DRB1 *0101, DRB5*0101, DRB1*1501, DRB1*0301,
      DRB1*0401, DRB1*1402, and DRB3*0102, as demonstrated using a panel of DR gene
      transfected L cells. The TCR gene usage was also heterogeneous. V beta 5.2, a
      peptide of which is currently being used in a clinical trial for treatment of MS
      patients, was expressed by only one of our TCL. However, within this complex
      pattern of MBP-specific T cell responses, a minority of MS patients were found to
      exhibit a more restricted response with respect to their TCL epitope specificity.
      In these patients 75-87% of the TCL responded to a single, patient-specific
      cluster of immunodominant T cell epitopes located within a small (20-amino acid)
      domain of MBP. These nested clusters of immunodominant epitopes were noted within
      the amino acids 80-105, 108-131, and 131-153. The T cell response to the
      immunodominant epitopes was not monoclonal, but heterogeneous, with respect to
      fine specificity, TCR usage, and even HLA restriction. In one patient (H.K.),
      this restricted epitope profile remained stable for > 2 yr. The TCR beta chain
      sequences of TCL specific for the immunodominant region of HK are consistent with
      an oligoclonal response against the epitopes of this region (80-105). Further,
      two pairs of identical sequences were established from TCL generated from this
      patient at different times (June 1990 and June 1991), suggesting that some TCL
      specific for the immunodominant region persisted in the peripheral repertoire.
      The possible role of persistent immunodominant epitope clusters in the
      pathogenesis of MS remains to be established.

PMID- 7504691
TI  - Nonsense mutation R1162X of the cystic fibrosis transmembrane conductance
      regulator gene does not reduce messenger RNA expression in nasal epithelial
      tissue.
AB  - Cystic fibrosis (CF) patients bearing the premature translation termination
      mutation (nonsense mutation) W1282X present severe pulmonary and pancreatic
      disease, whereas patients carrying other nonsense mutations such as G542X, R553X,
      S1255X, R1162X, and W1316X show a severe pancreatic but mild pulmonary illness.
      CF gene expression was found absent in respiratory tissues with mutations R553X
      and W1316X, which led to the hypothesis that the absence of the gene product in
      the lung is more favorable than the presence of an altered one. We asked whether
      or not all the nonsense mutations characterized by mild pulmonary disease
      phenotypes do present the absence of CF gene expression. We therefore
      investigated gene expression at the mRNA level in respiratory cells obtained from
      nasal polyps from a patient homozygous for the R1162X mutation. Gene expression
      was studied by amplification with polymerase chain reaction of segments of the CF
      transmembrane conductance regulator cDNA that was obtained by reverse
      transcription of RNA. Semiquantitative analysis was performed by Northern
      analysis. By comparing the data obtained from polyps deriving from non-CF
      subjects and a CF patient homozygous for dF508 mutation, it is shown that no
      reduction of CF gene expression is evident in R1162X respiratory tissue. We
      conclude that CF nonsense mutations have heterogeneous mechanisms of gene
      expression.

PMID- 7504692
TI  - E-selectin supports neutrophil rolling in vitro under conditions of flow.
AB  - E-selectin was evaluated for its ability to support neutrophil adhesion under
      conditions of flow. At a wall shear stress of 1.85 dyn/cm2, neutrophils were
      found to attach to E-selectin expressed on the apical surface of L cell
      monolayers. The initial intercellular contact was most often evidenced by
      neutrophils rolling on the monolayer at a mean rate of congruent to 10 microns/s.
      Anti-E-selectin monoclonal antibody, CL2/6, inhibited this interaction by > 90%.
      Rolling neutrophils often transiently stopped, but in contrast to the behavior on
      stimulated endothelial cells, they remained spherical in shape and did not
      migrate on or beneath the monolayer. A possible contribution of neutrophil L
      selectin to this interaction was indicated by the findings that anti-L-selectin
      monoclonal antibody, DREG-56, inhibited E-selectin-dependent adhesion under flow
      by > 65%, and there was a highly significant correlation between surface levels
      of L-selectin and E-selectin-dependent adhesion under flow. E-selectin also
      appeared to support neutrophil adhesion to IL-1 beta-stimulated endothelial cells
      under conditions of flow, but it accounted for only congruent to 30% of the level
      of adherence, in contrast to L-selectin which accounted for > 65%. Thus, both L
      selectin and E-selectin can support neutrophil adhesion at wall shear stresses
      that preclude intercellular adhesion molecule-1-dependent adhesion, and they
      participate in neutrophil adherence to stimulated endothelial cells under
      conditions of flow.

PMID- 7504693
TI  - Patch-clamp evidence for calcium channels in apical membranes of rabbit kidney
      connecting tubules.
AB  - To test the hypothesis that Ca channel plays a role in renal epithelial Ca
      transport, we exposed and patched apical membranes of freshly microdissected
      rabbit connecting tubules (CNTs). Single channel Ca currents were recorded with
      Ba as the charge carrier. In the cell-attached mode, 8-Br-cAMP increased the open
      state probability (Po) to 0.6%. In excised, inside-out patches, Po was low
      spontaneously and remained low during either bath protein kinase A catalytic
      subunit (PKAcs) or Bay K 8644. Exposure to both agonists, however, unmasked Ca
      channels previously latent with only one, raising Po by 1.05% at membrane
      potential of -70 mV. Mean Po for 14 seals (2.57%) peaked at -70 mV, declining
      with either hyperpolarization or depolarization. The slope conductance was 25 pS.
      The extrapolated reversal potential (138 mV) agrees with the calculated
      equilibrium potential for Ca (158 mV). The Ca to Na permeability ratio exceeded
      2,800. In four patches stimulated by Bay K 8644 and PKAcs, bath nifedipine
      reduced Po from 1.03 to 0.15% at -63 mV. These patch-clamp data demonstrate a
      selective, 25-pS, cAMP/PKAcs-sensitive Ca channel in apical membranes of CNT. Po
      is stimulated by PKAcs and dihydropyridine (DHP) agonist, but inhibited by DHP
      antagonist and by depolarization. The data are consistent with the potential role
      of apical membrane Ca channel in epithelial Ca transport.

PMID- 7504694
TI  - Cardiac alpha-myosin heavy chains differ in their induction of myocarditis.
      Identification of pathogenic epitopes.
AB  - BALB/c mice develop autoimmune myocarditis after immunization with mouse cardiac
      myosin, whereas C57B/6 mice do not. To define the immunogenicity and
      pathogenicity of cardiac myosin in BALB/c mice, we immunized mice with different
      forms of cardiac myosin. These studies demonstrate the discordance of
      immunogenicity and pathogenicity of myosin heavy chains. The cardiac alpha-myosin
      heavy chains of BALB/c and C57B/6 mice differ by two residues that are near the
      junction of the head and rod in the S2 fragment of myosin. Myosin preparations
      from both strains are immunogenic in susceptible BALB/c as well as in
      nonsusceptible C57B/6 mice; however, BALB/c myosin induces a greater incidence of
      disease. To further delineate epitopes of myosin heavy chain responsible for
      immunogenicity and disease, mice were immunized with fragments of genetically
      engineered rat alpha cardiac myosin. Epitopes in the region of difference between
      BALB/c and C57B/6 (residues 735-1032) induce disease in both susceptible and
      nonsusceptible mice. The data presented here demonstrate that pathogenic epitopes
      of both mouse and rat myosin residue in the polymorphic region of the S2 subunit.
      In addition, these studies suggest that polymorphisms in the autoantigen may be
      part of the genetic basis for autoimmune myocarditis.

PMID- 7504695
TI  - Mithramycin selectively inhibits collagen-alpha 1(I) gene expression in human
      fibroblast.
AB  - The products of the collagen-alpha 1(I) and -alpha 2(I) genes form the triple
      helical molecule collagen type I, which constitutes the major ECM protein in
      tissue fibrosis. The collagen-alpha 1(I) gene is mainly transcriptionally
      regulated, and its promoter activity depends on the interaction of the
      transcription factors NF-I and Sp1 with a tandem repeat of evolutionary conserved
      NF-I/Sp1 switch elements. An increased affinity of Sp1 to these elements has been
      observed in experimental liver fibrosis. Here, we demonstrate that the DNA
      binding drug mithramycin displays a high affinity binding to the GC-rich elements
      in the collagen-alpha 1(I) promoter as measured by DNAse I protection and gel
      retardation assays. Mithramycin interferes with Sp1 but not with NF-I binding to
      these sites. At a concentration of 100 nM, mithramycin efficiently reduces basal
      and TGF-beta-stimulated alpha 1(I) gene expression in human primary fibroblasts.
      The transcriptional activity and mRNA steady state levels of other genes,
      including the collagenase gene, as well as the growth rate of fibroblasts
      remained unchanged on exposure to this drug. Taken together, our results indicate
      that the transcriptional activity of the type I collagen gene highly depends on
      its GC-rich regulatory elements, and further, that these elements can be
      differentially blocked, thereby changing the balance between ECM structural and
      degrading gene activities in human fibroblasts.

PMID- 7504696
TI  - Gray platelet syndrome. Dissociation between abnormal sorting in megakaryocyte
      alpha-granules and normal sorting in Weibel-Palade bodies of endothelial cells.
AB  - The gray platelet syndrome (GPS) is a rare congenital bleeding disorder in which
      megakaryocytes and platelets are deficient in alpha-granule secretory proteins.
      Since the Weibel-Palade bodies (WPB) of endothelial cells as well as the alpha
      granules contain the von Willebrand Factor (vWF) and P-selectin, we examined by
      transmission electron microscopy the dermis capillary network of two patients
      with GPS. Endothelial cells showed the presence of normal WPB with typical
      internal tubules. Using single and double immunogold labeling for vWF and P
      selectin, we detected vWF within WPB, where it was codistributed with the
      tubules, whereas P-selectin delineated the outline of WPB. Therefore, the
      fundamental targeting defect in GPS is specific to the megakaryocytic cell line.

PMID- 7504697
TI  - Rolling and adhesion of human tumor cells on vascular endothelium under
      physiological flow conditions.
AB  - We investigated the interaction of different human tumor types with resting and
      IL-1-activated human umbilical vein endothelial cells under laminar flow
      conditions using a parallel plate flow chamber. Three tumor cell lines (the HT
      29M colon carcinoma, the OVCAR-3 ovarian carcinoma, and the T-47D breast
      carcinoma) showed limited adhesion to unstimulated endothelial cells at any of
      the shear stress levels tested, while rolling and massive adhesion of tumor cells
      were observed on IL-1-activated endothelial cells. Three other tumor cell lines
      (the A375M and A2058 melanomas and the MG-63 osteosarcoma) did not adhere on
      resting endothelial cells at high shear stress (> 1.5 dyn/cm2) and started to
      adhere with decreasing shear stress; the number of adherent cells increased
      steeply on IL-1-activated endothelial cells, but no cell rolling was observed
      even at the highest shear stress. These mechanisms of tumor cell interaction with
      endothelial cells were analyzed in detail using the HT-29M colon carcinoma and
      the A375M melanoma. Incubation of activated endothelial cells with a monoclonal
      antibody against E-selectin inhibited rolling and adhesion of HT-29M, but had no
      effect on the adhesion of A375M cells; monoclonal antibody against vascular cell
      adhesion molecule-1 reduced the adhesion of A375M cells and had no effect on HT
      29M. The selective interaction of these two molecules with tumor cells was
      confirmed by measuring the adhesion of tumor cells on immobilized soluble
      proteins. On E-selectin-coated surfaces, HT-29M cells rolled during perfusion
      experiments without subsequent adhesion, while A375M cells did not adhere. On
      vascular cell adhesion molecule-1-coated surfaces, HT-29M cells neither adhered
      nor rolled, while A375M cells adhered massively without rolling. Under flow
      conditions, therefore, cells from different tumor types interact with the
      endothelial surface by different mechanisms, depending on adhesion molecules
      expressed on the tumor and endothelial cell surface.

PMID- 7504698
TI  - Nitric oxide mediates interleukin-1-induced cellular cytotoxicity in the rat
      ovary. A potential role for nitric oxide in the ovulatory process.
AB  - Treatment of primary cultures of rat ovarian dispersates with IL-1 beta results
      in morphologic and cytotoxic changes, thought to reflect tissue remodeling events
      associated with ovulation. We examined the role that the free radical nitric
      oxide plays in this process and report that IL-1 beta induces expression of the
      inducible isoform of nitric oxide synthase in ovarian cells as demonstrated by
      immunoprecipitation. We show that IL-1 beta treatment results in the formation of
      nitric oxide (as measured by accumulation of nitrite and cGMP) in both a time-
      and concentration-dependent manner that is prevented by aminoguanidine, a
      selective inhibitor of the inducible isoform of nitric oxide synthase.
      Aminoguanidine also inhibits IL-1-induced ovarian cellular cytotoxicity. These
      results suggest that nitric oxide is an important mediator of cell death and may
      act as a physiologically significant mediator of tissue remodeling events that
      occur in vivo during the ovulatory process.

PMID- 7504699
TI  - Developmental disabilities among children between birth and 3 years old in the
      Haifa district: a population study.
AB  - The incidence of major neurodevelopmental deficits among children between birth
      and 3 years of age in the Haifa district was evaluated. Routine standardized
      developmental screening at the well-baby clinics was employed. The records of all
      children referred to the only two child developmental centers in the district
      during a period of 4 years were analyzed. The overall incidence was 31 per 1000
      and was lower than expected. The age at diagnosis and associated disorders are
      discussed. In 30% of the cohort the diagnosis was inaccurate, and a 22% false
      positive referral rate was noted. A more thorough training in the early diagnosis
      of psychomotor developmental problems in childhood in the well-baby clinics is
      indicated.

PMID- 7504700
TI  - Obstacles to effective developmental surveillance: errors in clinical reasoning.
AB  - Recent research and legislation support the importance of early identification
      and intervention for children with developmental and behavioral or emotional
      problems. Detecting these children often depends on medical professionals,
      especially pediatricians. However, few pediatricians use developmental screening
      tests to help them identify children. Rather, physicians usually rely on their
      clinical impressions to discriminate children with and without difficulties.
      Research on the accuracy of clinical impressions, although sparse, suggests that
      only half the children in need are identified. The most obvious reasons, such as
      severity of the problem or the type of clinical information physicians select
      (e.g., parents' concerns, observations of the child, history, etc.), do not fully
      explain why some children are identified and others are not. More complete
      explanations are found in research on clinical impression formation that suggests
      physician's selection from the array of clinical data is mediated by their unique
      experiences, beliefs, and attitudes. These qualities provide a set of judgment
      heuristics for sorting seemingly relevant from irrelevant information. Judgment
      heuristics, depending on their content, may lead to accurate or inaccurate
      impressions. This article suggests a model of ideal impression formation that may
      help physicians learn to more accurately identify children with developmental and
      behavioral or emotional problems.

PMID- 7504701
TI  - Histochemistry of mucin secreting components in mucoepidermoid and adenosquamous
      carcinoma of the oesophagus.
AB  - AIMS: To determine the direction of differentiation of the mucin secreting
      components in a rare group of oesophageal tumours--oesophageal squamous cell
      carcinomas with prominent mucin secreting components (mucoepidermoid carcinomas
      and adenosquamous carcinomas). METHODS: In a review of 617 cases of primary
      carcinoma of the oesophagus, 16 cases of squamous cell carcinoma with prominent
      mucin secreting components were studied using a battery of histochemical
      techniques. RESULTS: The mucin produced by these tumours was mixed and included a
      variable content of enzyme labile sialomucin (positive for mucicarmine, periodic
      acid Schiff, and alcian blue, and sensitive to sialidase digestion and negative
      for high iron diamine-alcian blue). Retrospective analysis of endoscopic biopsy
      specimens taken from these tumours showed that mucin was present in five (42%)
      cases. CONCLUSIONS: The glandular component of this group of tumours
      histochemically differentiated in the direction of oesophageal glands:
      examination of the mucin secreting component in squamous cell carcinoma in
      resected specimens is therefore required for recording the true incidence of this
      type of tumour.

PMID- 7504702
TI  - Quantitation of vitronectin in serum: evaluation of its usefulness in routine
      clinical practice.
AB  - AIMS: To make a preliminary assessment of the clinical relevance of serum
      vitronectin concentrations in various disease groups, using a recently available
      commercial radial immunodiffusion kit. METHODS: Serum vitronectin concentrations
      were measured in 80 control subjects and 144 patients with various diseases. The
      following characteristics were used to evaluate the test procedures: linearity of
      method, inter- and intrabatch precision, effect of storage, temperature and in
      vitro activation of the classical and alternative complement pathways on
      vitronectin concentrations. RESULTS: Significantly reduced serum vitronectin
      concentrations were found in patients with liver disease, renal disease, and
      systemic lupus erythematosus (SLE) (normal C3 and C4 concentrations, when
      compared with normal subjects. This particular method was suitable for measuring
      vitronectin concentrations in serum samples provided they were stored at -20
      degrees C. CONCLUSIONS: The clinical value of measuring serum vitronectin seems
      to be limited, but a larger study may be justified to ascertain the clinical
      importance of reduced serum vitronectin concentrations in liver diseases, and the
      possible role of vitronectin in other disease processes.

PMID- 7504703
TI  - Galanin immunoreactivity within the primate basal forebrain: evolutionary change
      between monkeys and apes.
AB  - Galanin immunoreactivity (GAL-ir) is differentially expressed within the basal
      forebrain of monkeys and humans. Most monkey magnocellular basal forebrain
      neurons colocalize GAL-ir. In contrast, virtually no human magnocellular basal
      forebrain neurons express GAL-ir. Rather, an extrinsic galaninergic fiber plexus
      innervates these neurons in humans. The present study examined the expression of
      GAL-ir within the basal forebrain of apes to establish the phylogenetic level at
      which this transformation occurs. The staining patterns of GAL-ir within the
      basal forebrain of both lesser (gibbons) and great (chimpanzee and gorilla) apes
      were compared to that previously observed within monkeys and humans. All apes
      displayed a pattern of basal forebrain GAL-ir indistinguishable from humans. GAL
      ir was not expressed within ape basal forebrain magnocellular neurons as seen in
      monkeys. Rather like humans, a dense collection of GAL-ir fibers was seen in
      close apposition to magnocellular perikarya. In addition, a few GAL-ir
      parvicellular neurons were scattered within the ape basal forebrain. These data
      indicate that the evolutionary change in the expression of GAL-ir within the
      primate basal forebrain occurs at the branch point of monkeys and apes.

PMID- 7504704
TI  - A study of macrophages, macrophage-related cells, and endothelial adhesion
      molecules in recurrent aphthous ulcers in HIV-positive patients.
AB  - The purpose of this immunohistochemical study was to investigate the presence and
      distribution of macrophages (CD11c+ and CD68+) and macrophage-related dendritic
      cells (factor XIIIa+ and CD36+) in early and late aphthous ulcers associated with
      HIV infection. To substantiate a mechanism by which these cells may move from the
      vascular compartment to tissue spaces, we also investigated expression of ELAM
      (endothelial leukocyte adhesion molecule), ICAM-1 (intercellular adhesion
      molecule), and CD18 (leukocyte function antigen). Numerous CD11c+ and CD68+
      macrophages were seen in early lesions, though larger numbers of CD68+ cells were
      present in older lesions. No significant increases in factor XIIIa+ dendrocytes
      were seen in either early or late lesions, though dendrocytes appeared enlarged.
      CD36+ cells and CD18+ leukocytes were more numerous in early than in late
      aphthous ulcers. ELAM and ICAM expression was most intense on endothelial cells
      in early aphthous ulcers, with staining intensity fading toward the lesion
      periphery. Control specimens showed weaker ELAM and ICAM staining than did the
      ulcer specimens. Keratinocytes did not express ICAM. By virtue of their numbers,
      macrophages and macrophage subtypes appear to have a significant role in both the
      early and late stages of this disease. Although factor XIIIa-expressing
      dendrocytes may not have been more numerous in the ulcers, they appeared to be
      "activated" because of their prominence in the lesions and their occasional co
      expression of CD68 antigen (KP1+). They may have a minor role in antigen
      processing, phagocytosis, and fibroplasia. ELAM and ICAM expression by
      endothelial cells provides a mechanism by which macrophages and other leukocytes
      can be recruited to the site of the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504705
TI  - Impulse control disorders.

PMID- 7504706
TI  - Induction of immediate-early genes by angiotensin II and endothelin-1 in adult
      rat cardiomyocytes.
AB  - OBJECTIVE: Few molecular signals for induction of myocardial hypertrophy have
      been identified. This study was carried out to investigate the action of
      angiotensin II and endothelin on the growth- and differentiation-related genes
      Egr-1 (early growth response gene 1) and c-fos in isolated adult rat
      cardiomyocytes. METHODS: Cardiac myocytes from male Wistar-Kyoto rats were
      isolated and incubated with angiotensin II and endothelin-1 in Dulbecco's
      modified Eagle's medium. RNA was isolated and blotted, and densitometric analysis
      was performed. All experiments were repeated at least three times. RESULTS:
      Endothelin-1 (10(-7) mmol/l) induced a 20-25-fold rise in Egr-1 messenger RNA
      within 15 min. This effect was dose-dependent. c-fos was induced 10-20-fold
      within 15 min with similar dose-response characteristics. Angiotensin II also
      induced Egr-1 and c-fos with kinetics similar to endothelin but a cofactor from
      fetal calf serum was needed for full c-fos expression. The protein kinase C
      activator phorbol 12-myristate 13-acetate also induced Egr-1. CONCLUSIONS: The
      results identify Egr-1 and c-fos as target genes for the action of endothelin and
      angiotensin II in the adult myocardium suggesting that induction of the genes may
      be part of the signal transduction pathway for angiotensin II and endothelin in
      the myocardium.

PMID- 7504707
TI  - CD40 expression in malignant plasma cells. Role in stimulation of autocrine IL-6
      secretion by a human myeloma cell line.
AB  - Myeloma is a neoplasia characterized by the accumulation of malignant plasma
      cells in the bone marrow. In these studies, we have demonstrated that CD40 is
      expressed in human myeloma cells and have used a recently established IL-6
      dependent myeloma cell line, ANBL-6, to examine the potential function of CD40
      expression in myeloma cells. In addition to its expression on the ANBL-6 cells,
      we show that CD40 is expressed on freshly isolated myeloma cells from seven of
      seven patients tested. To address the role of CD40 expression in myeloma cells,
      we have examined the responsiveness of the ANBL-6 cell line to a CD40-specific
      mAb, G28-5. This cell line has previously been shown to proliferate only in
      response to IL-6. Of interest in this study, G28-5 also induced proliferation of
      the ANBL-6 cells. This proliferation was substantially inhibited by an IL-6
      neutralizing mAb. Analysis of ANBL-6 cell culture supernatants by ELISA
      demonstrated that G28-5-stimulated cells secreted significant levels of IL-6,
      whereas unstimulated cell culture supernatants contained undetectable levels of
      IL-6. Furthermore, CV-1/EBNA cells expressing the human CD40 ligand also induced
      the proliferation of the ANBL-6 cell line, an effect that was inhibited by the
      anti-IL-6 mAb. Lastly, RNA blot analysis demonstrated an increase in IL-6 message
      in G28-5-stimulated ANBL-6 cells over unstimulated cells. These results indicate
      that the primary mechanism of anti-CD40-stimulated proliferation of the ANBL-6
      cells is the induction of autocrine IL-6 production. Moreover, these data suggest
      that the expression of CD40 in malignant plasma cells may play a role in tumor
      cell expansion, possibly by stimulating the induction of autocrine IL-6
      secretion.

PMID- 7504708
TI  - A peptide sequence mimics the epitope on the multideterminant antigen (Tyr,Glu)
      Ala-Lys that induces the dominant H10/V kappa 1+ primary antibody response.
AB  - The multideterminant Ag (Tyr,Glu)-Ala-Lys [(T,G)-A-L] elicits a heterogeneous
      secondary antibody response to different epitopes consisting of side-chain or
      backbone residues. However, the primary response is restricted and dominated by
      side-chain specific antibodies that also bind a random, linear copolymer of L-Glu
      and L-Tyr (GT+ antibodies), share TGB5 Id, and use the H10/V kappa 1 germ-line
      gene combination. We analyzed several defined sequence peptides to determine
      whether any might mimic the side-chain epitope(s) on (T,G)-A-L which induce the
      dominant Id+, H10/V kappa 1+ primary response. A carrier conjugate of the peptide
      TyrGluGluGluGluTyrTyrGluGluGluGluTyr (called TG4) was recognized by all the (T,G)
      A-L-induced, GT+ hybridoma antibodies analyzed. In the splenic focus assay, the
      majority of primary and memory B cell clones induced by (T,G)-A-L produced
      antibodies that recognized the TG4 peptide. Mice immunized with TG4 conjugated to
      human gamma globulin (HGG) produced antibodies that bound (T,G)-A-L and were TGB5
      Id+. Molecular analysis of Id+ primary hybridomas from TG4-HGG immunized mice
      showed that the antibodies used the H10 and V kappa 1 germ-line genes. Thus, the
      TG4 peptide can be bound by Id+, GT+ anti-(T,G)-A-L antibodies, and it induces
      Id+ antibodies that use the H10/V kappa 1 gene combination. By these criteria,
      the TG4 peptide mimics the side-chain epitope(s) on (T,G)-A-L that induces the
      dominant primary antibody response to that multideterminant Ag.

PMID- 7504710
TI  - Stem cell factor induces mast cell adhesion to fibronectin.
AB  - Stem cell factor (SCF) or c-kit ligand is a growth factor cytokine produced by
      stromal cells that is known to influence mast cell proliferation and
      differentiation. We hypothesized that SCF may also influence the adhesion of mast
      cells to connective tissue matrix. To examine this hypothesis, we stimulated
      MCP5/L mast cells or murine bone marrow-derived cultured mast cells (BMCMC) with
      either SCF or PMA and observed adhesion to fibronectin (FN). As expected, 80 to
      90% of PMA-activated MCP5/L cells or BMCMC adhered to FN. In addition, SCF
      promoted MCP5/L cell or BMCMC adhesion to FN in a dose-response fashion with 50
      to 60% of BMCMC adhering to FN at a concentration 10 ng/ml of SCF. BMCMC adhesion
      was observed with as little as 200 pg/ml of SCF. Adhesion of SCF stimulated BMCMC
      to FN did not require IL-3, but was dependent on the concentration of FN used to
      coat the assay surface. Mast cell adhesion in the presence of SCF appeared to
      occur through an integrin receptor as adhesion was calcium dependent and could be
      blocked by an RGD (Ang, Gly, Asp)-containing peptide. SCF did not directly
      mediate adhesion through interaction with c-kit, as FN-coated surfaces exposed to
      SCF before initiation of the adhesion assay did not promote adhesion in the
      absence of soluble SCF. Rather, SCF appeared to stimulate adhesion to FN by
      activating mast cells through its interaction with c-kit. Thus, antibody to SCF
      blocked adhesion, and rat and murine SCF stimulated BMCMC adhesion to FN, but
      human SCF, which does not bind to murine c-kit, did not stimulate adhesion.
      Genistein, which inhibits tyrosine kinase activity, partially inhibited SCF
      induced adhesion. SCF thus stimulates mast cell adhesion and, because SCF is
      produced normally in tissues, it may be a major factor responsible for the
      adhesion of mast cells to connective tissue matrix under physiologic conditions.

PMID- 7504709
TI  - T and B epitope determination and analysis of multiple antigenic peptides for the
      Schistosoma mansoni experimental vaccine triose-phosphate isomerase.
AB  - Schistosoma mansoni triose-phosphate isomerase (TPI), a glycolytic enzyme, was
      originally identified as the target of the mAb M.1 that conferred protection when
      the antibody was administered in vivo. In this study we increase the evidence
      that schistosome TPI is a potential vaccine Ag by showing that it also a potent
      inducer of IL-2 and IFN-gamma production (Th1 responses), driving production of
      these cytokines in the same cell populations of infected animals that have high
      Th2 responses directed at other parasite egg Ag. With the goal of synthetic
      peptide vaccine design, rTPI was used to determine specific T and B cell epitopes
      recognized by two strains of mice representing high and moderate responders
      (C57Bl/6J and CBA/J). All selected epitopes were from nonconserved regions of TPI
      and thus parasite-specific. We then defined minimal size immunoreactive epitopes
      and synthesized four-armed multiple antigenic peptides (MAP) consisting of T and
      B cell epitopes that could be recognized by both strains of mice in the same
      molecule. Characterization of the immunoreactivity of the MAP showed that higher
      antibody recognition of the MAP was attained when the B cell epitope was placed
      on the amino termini relative to the T cell epitope, whereas equivalent
      immunoreactivity occurred for the T cell epitopes when located at either
      position. Most interesting was the finding that one of the minimal T cell
      epitopes, when incorporated into the MAP, required enlarging to retain
      immunoreactivity. Finally we showed that both the full-length TPI molecule and
      the final version of the MAP were immunogenic to T cells in naive animals and
      induced cross-recognition in the form of IL-2 and IFN-gamma production.

PMID- 7504711
TI  - CD40-activated surface IgD-positive lymphocytes constitute the long term IL-4
      dependent proliferating B cell pool.
AB  - In vitro, B cells undergo long term proliferation when triggered through their
      CD40 surface molecule and in the presence of IL-4. Here, we show that cells that
      proliferate in this culture system lose their germinal center (GC) features and
      acquire or maintain non-GC markers. When separated by the magnetic cell
      separation system, both sIgD+ and sIgD- B cells can proliferate in this culture
      system, sIgD+ B cells exhibiting a higher rate of growth than sIgD- cells.
      Simultaneous flow cytometric measurement of sIgD and DNA content revealed that B
      lymphocytes can keep their sIgD after entry into cell cycle. Experiments using G8
      Id-positive B lymphocytes allowed us to follow the evolution of sIgD+ and sIgD-
      cells in a reconstituted B cell population. Long term proliferating cells are
      sIgD+/sIgM(+)-derived B lymphocytes whereas the initial sIgD-/sIgM- cells are
      lost. Taken together, these data show that anti-CD40 + IL-4 activated sIgD+ B
      blasts express non-GC characteristics and that sIgD+ B cells preferentially
      proliferate in the CD40 system. The possible in vivo role of IL-4 + CD40
      signaling is discussed.

PMID- 7504712
TI  - Tyrosine kinase-dependent assembly of actin plaques linking Fc epsilon R1 cross
      linking to increased cell substrate adhesion in RBL-2H3 tumor mast cells.
AB  - RBL-2H3 rat tumor mast cells form monolayers on various surfaces without
      assembling specialized adhesion structures at the cell substrate interface.
      Incubation of RBL-2H3 cells with Ag that cross-link the high affinity IgE
      receptor, Fc epsilon R1, activates at least two receptor-associated protein
      tyrosine kinases, Syk and Lyn, and elicits secretion and F-actin assembly,
      membrane ruffling, and increased spreading and adhesion. Herein, we report that
      Fc epsilon R1 cross-linking also causes the assembly in cell monolayers of a
      network of F-actin-rich plaques that form footlike processes at contact sites
      between the plasma membrane and the underlying substratum. Sheets of F-actin-rich
      ventral plasma membrane-bearing actin plaques are left on the substrate when
      monolayers of activated cells are displaced by incubation with ZnCl2 followed by
      shearing in a stream of buffer; in contrast, most unstimulated cells are
      completely displaced or leave only fragile membrane fragments. These observations
      link actin plaque assembly to increased cell substrate adhesion. Actin plaques
      disassemble rapidly in the presence of monovalent hapten, indicating their
      dependence on continued Fc epsilon R1 cross-linking. They accumulate antibody to
      phosphotyrosine and disassemble rapidly in the presence of the protein tyrosine
      kinase inhibitor, piceatannol, indicating their additional dependence on tyrosine
      kinase activation. Structures resembling actin plaques form when RBL-2H3 cell
      monolayers are incubated with the protein tyrosine phosphatase inhibitor, vanadyl
      hydroperoxide, in the presence of PMA, which increases actin polymerization. It
      is likely that the tyrosine kinase-dependent assembly of actin plaques plays an
      important role in linking the activation of signaling receptors to adhesive
      responses in RBL-2H3 and other immune system cells.

PMID- 7504713
TI  - The suppressor factor of T suppressor cells induced by tolerogenic conjugates of
      ovalbumin and monomethoxypolyethylene glycol is serologically and
      physicochemically related to the alpha beta heterodimer of the T cell receptor.
AB  - Ovalbumin-specific, H-2Kd restricted, CD8+ Ts cells of clone 17.2 were shown to
      produce an OVA-specific Ts cell factor (TsF17.2) possessing the same Ag
      specificity and MHC restriction as those of the intact Ts cells. The Ts cell
      clone was generated from a single cell of the spleen of a mouse which had been
      immunosuppressed by injection of tolerogenic OVA(mPEG)12 conjugate. For the
      elucidation of the nature of TsF17.2, it was characterized by serologic,
      physicochemical, and Western blot analyses. It was found that 1) the OVA-specific
      suppression of in vitro antibody production by TsF17.2 could be blocked by mAb
      H28-710 which binds to an epitope of the constant region of the alpha-chain of
      TCR; 2) the TsF17.2 could be sequestered by, and eluted from, immunosorbents
      prepared by coupling to Affi-Gel Hz the H28-710 mAb or the mAb H57-597 and F23.1
      which are specific, respectively, for an epitope of the constant region of the
      beta-chain and an epitope of the V beta 8 region of the TCR; and 3) the TsF17.2
      had a pl of 7.0, m.w. of 84,000, and consisted of two disulfide-linked subunits
      of 42,000 each. After electroelution from the SDS-PAGE gel, the m.w. 84,000
      molecule retained its capacity to suppress in vitro antibody production in an OVA
      specific manner. From all these results it was concluded that this Ts cell factor
      may represent a soluble form of the alpha beta heterodimer of TCR of cloned Ts
      cells.

PMID- 7504715
TI  - [Reverse transcriptase gene analysis of HIV-1 mutants cultured in the presence of
      AZT].
AB  - HIV-1 strains were isolated from four patients treated with AZT for more than 6
      months and from three patients untreated with AZT. Isolates from patients treated
      with AZT have been cultured by passage of virus in cell culture in the presence
      of 1 microM AZT. However the isolates from patients untreated with AZT could not
      be cultured in the presence of AZT. The RT gene of HIV-1 isolates which had been
      cultured in the presence of AZT were amplified by PCR and cloned to M13 vector.
      Four amino acid mutations in RT gene (Asp67, Lys70, Thr215, Lys219) associated
      with resistance to AZT were analysed. All of the 22 clones obtained from the
      isolates in the presence of 1 microM AZT had mutations at codon 215(Thr-->Tyr or
      Phe). Some of the 22 clones also had other mutations at codon 67 (Asp-->Ser),
      codon 70 (Lys-->Arg) and codon 219 (Lys-->Glu or Gln). Four amino acid residues
      in RT gene of the isolates which had been cultured in the presence of AZT were
      compared to that of the isolates cultured in the absence of AZT. The clones of
      the isolates obtained from the patients (04 or 05) had mutations at only codon
      215 Thr-->Tyr) in both the presence and the absence of AZT. All of the clones of
      the isolates obtained from the patients (06 or 07) had mutations at codon 215 and
      some of them had other mutations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504714
TI  - Regulation of adhesion molecule expression in Kaposi's sarcoma cells.
AB  - Kaposi's sarcoma (KS) is a neoplasm with multifocal vascular lesions that is
      often seen in homosexual HIV-infected individuals. Infiltrates of leukocytes are
      characteristic components of KS lesions, and the products of leukocytes have been
      shown to enhance the proliferation of KS cells in vitro and most likely are
      crucial for the development of KS lesions in vivo. It is therefore likely that
      the expression of cellular adhesion molecules (CAM) is a critical determinant in
      the pathogenesis of KS by dictating the numbers and types of leukocytes that
      accumulate in areas predisposed to KS. We report that in the absence of inducers,
      KS cells in culture expressed low levels of ICAM-1 and undetectable VCAM-1 and E
      selectin. ICAM-1, VCAM-1, and E-selectin were all induced by dsRNA (poly (I:C)),
      IL-1 beta, TNF-alpha, and LPS in KS cells. All of these agents increased NF-kappa
      B binding activity in nuclear extracts from KS cells. Neither human dermal
      fibroblasts nor human aortic smooth muscle cells had detectable VCAM-1 protein
      expression in response to conditions that led to high levels of VCAM-1 expression
      in KS cells. Although E-selectin expression was induced in KS cells, the peak
      cell surface protein levels were less than 25% the levels achieved on HUVEC or
      human dermal microvascular endothelial cells (HMEC). These low levels resembled
      the levels that were induced in HMEC immortalized with SV 40 large T Ag. These
      data indicate that multiple proinflammatory agents can induce NF-kappa B binding
      activity and can enhance ICAM-1, VCAM-1, and E-selectin expression in KS cells.
      The increased CAM expression enhances leukocyte binding to KS cells. Thus, the
      induction of CAM expression could be an early event in the development of KS by
      recruiting leukocytes into KS lesions, thereby providing factors that could
      potentiate the development of KS.

PMID- 7504717
TI  - Evaluation of hyperechoic liver tumors in MHTS.
AB  - Hepatocellular carcinoma (HCC) shares only a small proportion of hyperechoic
      liver tumors detected in MHTS and mimics hemangioma on ultrasonography (US). The
      precise diagnosis of HCC is hence difficult in MHTS, but presence or absence of
      underlying chronic liver disease and serum alfa-fetoprotein (AFP) titer might
      provide useful informations.

PMID- 7504719
TI  - Cocaine-induced c-fos messenger RNA is inversely related to dynorphin expression
      in striatum.
AB  - The effects of the indirect dopamine receptor agonist cocaine in the striatum on
      levels of mRNAs of the immediate-early gene c-fos and the neuropeptides
      dynorphin, substance P, and enkephalin were analyzed with quantitative in situ
      hybridization histochemistry. Both single (acute) and repeated (twice a day for 4
      d) systemic injections of cocaine (3.75-30 mg/kg) to rats resulted in dose
      dependent, regionally specific elevations of mRNA expression in striatal neurons.
      A single drug treatment elevated c-fos mRNA expression, whereas repeated
      treatments resulted in little c-fos expression but elevated dynorphin mRNA
      levels. Both the regional and temporal patterns of gene expression revealed an
      inverse relationship between dynorphin and c-fos expression. This relationship
      was examined in a time course experiment in which cocaine (30 mg/kg) was
      administered for 1, 2, 3 or 4 d. Basal levels of dynorphin expression were
      relatively high in the ventral striatum, including the nucleus accumbens, a
      ventrolateral region, and an area along the medial bank of the striatum. A single
      injection of cocaine induced c-fos mRNA in striatal areas with low basal
      expression of dynorphin. Thus, c-fos mRNA induction was highest in the dorsal
      central striatum, where basal dynorphin mRNA levels were lowest. In this region,
      dynorphin mRNA expression increased on subsequent treatment days parallel to
      diminished c-fos mRNA induction. Changes in substance P. mRNA levels appeared to
      match directly both the temporal and regional patterns of c-fos induction.
      Enkephalin mRNA expression was altered, but only slightly, by these cocaine
      treatments. Statistical analysis of the regional patterns of basal and altered
      mRNA levels shows a unique inverse relationship between basal dynorphin
      expression and c-fos induction by cocaine. Further evidence of this relationship
      is provided by the dose-dependent blockade of cocaine-induced c-fos expression by
      spiradoline, a dynorphin agonist. Together, these results suggest that the
      restricted regional pattern of cocaine-induced c-fos expression is related, in
      part, to the basal level of dynorphin expression, and that cocaine treatment
      elevates dynorphin expression in striatal regions with a strong c-fos response,
      thereby limiting subsequent c-fos induction by cocaine. These findings lead to
      the hypothesis that dynorphin acts to regulate the responsiveness of striatal
      neurons to dopamine stimulation.

PMID- 7504718
TI  - Hepatocellular carcinoma: the diagnostic difficulties of ultrasonography and
      analysis of risk factors in MHTS.
AB  - Thirty-nine cases of hepatocellular carcinoma (HCC) out of 55,135 examinees were
      examined. The diagnostic problems of ultrasonography (US) in detecting HCC and
      the risk value of 10 factors in HCC were discussed. We also propose the
      surveillance programs for HCC in Multiphasic Health Testing and Services (MHTS).
      US will be performed at 3-, or 6 monthly intervals in conjunction with AFP
      monitoring for the examinees over 50 males and over seventy females with liver
      dysfunction (GOT > 38 IU/ml) is recommended.

PMID- 7504716
TI  - Molecular mimicry: any role in the pathogenesis of spondyloarthropathies?
AB  - Ankylosing spondylitis and reactive arthritis are seronegative
      spondyloarthropathies, which are strongly associated with HLA-B27. Despite
      intensive investigation, the basis for this association is not clear. However, in
      recent years one favored hypothesis to explain this linkage has been that of
      molecular mimicry, i.e., sharing of linear or conformational epitopes common to
      microbial antigens and host structures. During the past few years several
      examples of molecular mimicry between HLA-B27 and microbial antigens have been
      described. Heat shock proteins, among others, have been considered as target
      candidates for autoimmune phenomena, because of the high degree of homology
      between bacterial and mammalian species. Reactive arthritis triggered by Yersinia
      or Salmonella provides a unique model for studying the pathogenetic mechanisms
      underlying human inflammatory joint diseases in general, because the
      arthritogenic microbes are known and well-characterized. We have described two
      bacterial proteins that share amino acid homology with HLA-B27, namely YadA
      (Yersinia adhesin) and OmpH, outer surface proteins of Yersinia and Salmonella,
      respectively. Notably, the area of identity of these amino acid sequences is
      located in the same place on the HLA-B27 molecule as a hexapeptide identical
      between Klebsiella nitrogenase and HLA-B27, and a pentapeptide shared by a
      Shigella flexneri protein and HLA-B27. We have investigated immune responses to a
      panel of synthetic peptides based on the HLA-B27-homologous portions of pathogen
      specific antigens in patients with reactive arthritis and ankylosing spondylitis.
      One third of the patients have antibodies to the synthetic peptides. However,
      instead of recognizing the HLA-B27-homologous portion, the antibodies are
      directed against the flanking sequences of the synthetic peptides. The concept of
      the role of molecular mimicry between HLA-B27 and microbial antigens in the
      pathogenesis of spondyloarthropathies is discussed, with a conclusion that no
      convincing evidence for its significance exists at the present.

PMID- 7504720
TI  - Correlation between insulin-like growth factor (IGF)-binding protein 5 and IGF-I
      gene expression during brain development.
AB  - Insulin-like growth factor (IGF)-binding proteins (IGFBPs) potently modulate the
      interactions of IGF-I and -II with the IGF-I receptor. Previous studies have
      shown that IGFBP2 gene expression is localized in astroglia, where it is
      anatomically and temporally coordinated with neuronal IGF-I expression during
      postnatal brain development. The present study shows that IGFBP5 gene expression
      is also highly abundant during brain development and also demonstrates
      significant spatiotemporal correlation with IGF-I, but exhibits a neuroanatomical
      distribution that is entirely distinct from IGFBP2. IGFBP5 and IGF-I mRNAs are
      synchronously coexpressed in principal neurons of sensory relay systems,
      including the olfactory bulb, medial and dorsal lateral geniculate bodies, and
      ventral tier, cochlear, lemniscal, and vestibular nuclei. They are also
      transiently coexpressed in principal neurons of the anterodorsal nucleus, but IGF
      I mRNA disappears from this structure shortly after birth, while IGFBP5 mRNA
      remains highly abundant here in the adult. IGFBP5 and IGF-I gene expression
      demonstrate a temporally coordinated laminar association in the developing
      cerebellar cortex and hippocampal formation. IGF-I mRNA is concentrated in
      Purkinje cells, while IGFBP5 mRNA is localized in the external germinal zone in
      the developing cerebellar cortex. IGFBP5 mRNA is transiently expressed in the
      retrosplenial and cingulate cortex, subiculum, Ammon's horn, and amygdala, while
      IGF-I mRNA is contemporaneously localized in large interneurons distributed
      throughout the hippocampal formation. IGFBP5 mRNA is localized in the lateral
      ventricular germinal zone at birth and remains in the subventricular zone into
      maturity. It is also detected in forebrain white matter tracts and olfactory
      nerve from the second week after birth into maturity. Thus IGFBP5, in addition to
      IGFBP2, may be a significant determinant of IGF action in the brain.
      Colocalization in some sites and paralocalization with IGF-I in other sites
      suggests the potential for autocrine and paracrine interaction between the
      binding protein and IGF-I in different settings. Arguments are advanced
      suggesting a role for IGFBPs in the targeting of IGF action to specific cell
      addresses during brain development.

PMID- 7504721
TI  - Corticospinal terminations in two new-world primates: further evidence that
      corticomotoneuronal connections provide part of the neural substrate for manual
      dexterity.
AB  - Anterograde transport of 2-10% WGA-HRP was used to examine the pattern of
      termination of efferents from the primary motor cortex to cervical segments of
      the spinal cord in cebus (Cebus apella) and squirrel (Saimiri sciureus) monkeys.
      We have compared the pattern of termination in these monkeys because of marked
      differences in their manipulative abilities. Both primates have pseudo-opposable
      thumbs; however, only cebus monkeys use independent finger movements to pick up
      small objects. We found that corticospinal terminations in cervical segments of
      the cebus monkey are located in three main zones: a dorsolateral region of the
      intermediate zone, a dorsomedial region of the intermediate zone, and the ventral
      horn. The projection to the ventral horn in these monkeys is particularly dense
      at C8-T1 segments, where terminations form a "ring" that encircles the lateral
      motoneuronal cell group. In contrast, there are only two main zones of
      terminations in the squirrel monkey: a dorsolateral region of the intermediate
      zone and a dorsomedial region of the intermediate zone. As others have noted,
      efferents from the primary motor cortex of squirrel monkeys have, at best, only
      sparse terminations within the ventral horn. Thus, there are marked differences
      between cebus and squirrel monkeys in the extent of corticospinal terminations
      within the ventral horn. These observations provide further support for the
      concept that monosynaptic projections from the primary motor cortex to
      motoneurons in the ventral horn provide part of the neural substrate for
      dexterous movements of the fingers.

PMID- 7504722
TI  - Intraseptal galanin potentiates scopolamine impairment of delayed nonmatching to
      sample.
AB  - Galanin coexists with ACh in the basal forebrain and medial septal region. The
      present study investigated the interactions of the muscarinic receptor antagonist
      scopolamine and the neuropeptide galanin on an operant spatial delayed non
      matching to sample task (DNMTS) in rats. Scopolamine administered both
      intraperitoneally and microinjected into the medial septum impaired performance
      on DNMTS. Galanin administered alone into the medial septum did not disrupt
      DNMTS, but potentiated the disruptive effects of intraperitoneal administered
      scopolamine. These findings raise the possibility that endogenous galanin may
      exacerbate cognitive impairments associated with forebrain cholinergic deficits.

PMID- 7504723
TI  - Presynaptic inhibition of excitatory synaptic transmission mediated by alpha
      adrenergic receptors in area CA3 of the rat hippocampus in vitro.
AB  - We have investigated the action of norepinephrine (NE) on excitatory synaptic
      transmission in the hippocampus by recording from CA3 pyramidal cells in
      organotypic slice cultures. NE (5 microM) was found to decrease the amplitude of
      pharmacologically isolated EPSPs elicited with stimulation of mossy fibers or
      recurrent axon collaterals (mean decrease in EPSP amplitude, 44%).
      Desensitization was observed with repetitive applications. NE did not affect the
      sensitivity of CA3 cells to iontophoretically applied AMPA, and did not affect
      the amplitude distribution of TTX-resistant, miniature excitatory synaptic
      currents. These data suggest that NE acts at presynaptic receptors to decrease
      glutamate release. This action of NE was blocked by the alpha receptor antagonist
      phentolamine and the specific alpha 1 receptor antagonist prazosine, but not by
      the beta receptor antagonist timolol or the alpha 2 receptor antagonist idazoxan.
      Inhibition of EPSPs by NE was prevented by pretreatment of cultures with
      pertussis toxin, indicating that G-proteins couple these receptors to their
      effectors. Stimulation of protein kinase C with phorbol ester blocked the action
      of NE on EPSPs. This effect, as well as the desensitization of NE responses, was
      reduced by application of the protein kinase inhibitor staurosporin. Presynaptic
      inhibition of excitatory synaptic transmission, mediated by alpha adrenergic
      receptors, represents a novel modulatory action of NE in the hippocampus.

PMID- 7504725
TI  - [Pharmaceutical characterization of silicone elastomer implant system containing
      chlormadinone acetate for prevention of estrus in bitches].
AB  - We developed a new subdermal silicone elastomer implants containing chlormadinone
      acetate (CMA), which was effective for prevention of estrus in bitches. The
      implants gave a continuous CMA release over a year. The CMA release from the
      implants was dependent on the CMA loading level and surface area of the implants.
      The CMA release patterns both in vitro and in vivo system fitted well with the
      Higuchi square root low. The dissolution test using organic solvents was found to
      be useful for the brief estimation of CMA release from the implants.

PMID- 7504724
TI  - Three-year incidence study of retroviral and viral hepatitis transmission in a
      Peruvian prostitute population.
AB  - A Peruvian female prostitute population was evaluated over a 3-year period to
      determine the incidence and risk factors of retroviral and viral hepatitis
      transmission. At three survey periods, a questionnaire was administered and serum
      samples were obtained. A total of 966 subjects were studied, with 34% followed
      for 38 months, 22% followed for 18 months, and 44% evaluated just once. On
      initial evaluation, 3 (0.3%) had HIV-1 antibody, 170 (17.6%) had HTLV-I antibody,
      578 (59.8%) had anti-HBc, and 7 (0.7%) had antibody to hepatitis C virus. The
      mean annual incidence of HTLV-I and hepatitis B infection was 1.6% and 4.7%,
      respectively. Univariate and logistic regression analysis of prevalence data
      indicated an association between sexual activity and HTLV-I and hepatitis B
      infection, but no independent risk factors were identified in cohort analysis.
      Parenteral risk factors were not associated with transmission, except for a small
      percentage of subjects who may have acquired hepatitis B infection from blood
      transfusions. These findings suggest that there is a high incidence of HTLV-I and
      hepatitis B infection from heterosexual contact in this female prostitute
      population.

PMID- 7504726
TI  - Inhibitory synaptic currents in stellate cells of rat cerebellar slices.
AB  - 1. In thin cerebellar slices of rats aged 14-21 days, voltage-gated currents,
      synaptic currents and GABA responses were studied with the tight-seal whole-cell
      recording technique from stellate cells (8-9 micrograms soma diameter) located in
      the outer two-thirds of the molecular layer. 2. In symmetrical Cl- conditions,
      stellate cells voltage-clamped at -60 mV showed spontaneous inhibitory
      postsynaptic currents (IPSCs). As were the GABAA responses of the same cells, the
      IPSCs were blocked by bicuculline. The frequency of occurrence of IPSCs ranged
      from 0.2 to 1.9 events per second (21 cells). The mean amplitude of the events
      ranged from 61 to 226 pA (mean +/- S.E.M.: 132 +/- 11; n = 21). 3. The temporal
      course of IPSCs was characterized by a rapid rise (mean +/- S.E.M. of the time to
      peak: 1.1 +/- 0.1 ms, n = 7) and a slow decay. The decay phase was described by a
      double exponential function with time constants of 8.7 +/- 0.6 ms, and 40.9 +/-
      3.7 ms respectively (means +/- S.E.M.; n = 7). 4. A minor fraction (15 to 20%) of
      the spontaneous synaptic events recorded in control saline had a faster onset
      than that of the IPSCs and decayed with a rapid mono-exponential decay (time
      constant of 1.0-1.3 ms). These were excitatory postsynaptic currents (EPSCs)
      unaffected by bicuculline and blocked by the glutamate receptor antagonist 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX). 5. Bath application of TTX (0.5-1
      microM), which blocked voltage-gated Na+ currents in stellate cells, induced a
      variable decrease in the frequency of IPSCs (mean +/- S.E.M. of the frequency
      ratio in TTX over control: 0.47 +/- 0.09; n = 12). However, the toxin had no
      significant effect either on the mean amplitude or on the kinetics of the IPSCs.
      The mean amplitude of the miniature IPSCs was 141 +/- 13 pA (mean +/- S.E.M.; n =
      22). 6. In TTX-containing solutions, the frequency of the IPSCs was unaffected
      when Ca2+ currents were eliminated either by removal of extracellular Ca2+ and
      addition of EGTA, or by addition of Cd2+. Miniature IPSCs of 200-300 pA were
      still observed. 7. In symmetrical Cl- conditions, local application of GABA to
      stellate cells induced an inward current and an increase in membrane noise.
      Responses to prolonged applications of GABA showed desensitization in both whole
      cell mode and somatic outside-out patches. The chord conductance estimated from
      recording single GABA channel events in somatic outside-out patches was 28
      pS.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504727
TI  - Evidence that capsaicin hyperaemia of rat sciatic vasa nervorum is local, opiate
      sensitive and involves mast cells.
AB  - 1. In previous work, we identified a prolonged and intense hyperaemic response of
      rat sciatic endoneurial vasa nervorum produced by epineurial application of
      capsaicin. We postulated that this response, which was blocked by substance P
      (SP) or calcitonin gene-related peptide (CGRP) antagonists, was a result of local
      release of neuropeptides on the 'feeding' epineurial vascular plexus. 2. In the
      present study, we evaluated factors that might influence capsaicin-induced
      hyperaemia of the rat sciatic endoneurium as measured by hydrogen clearance:
      central afferent connections, the epineurial vascular plexus, the release of
      histamine and administration of opiates. 3. Interruption of central afferent
      connections by proximal nerve section or removal of the epineurial vascular
      plexus did not influence baseline endoneurial perfusion. Plexus removal, but not
      proximal section, prevented capsaicin hyperaemia. 4. The epineurial vascular
      plexus was desensitized to the effect of capsaicin by prior application of
      capsaicin. Capsaicin hyperaemia was also prevented by: topical treatment with
      Spantide II ((D-NicLys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nl e11) substance P) an SP
      antagonist, systemic pretreatment with a combination of H1 and H2 histamine
      receptor antagonists, systemic pretreatment with cromolyn sodium or systemic
      pretreatment with morphine. None of these pretreatments influenced baseline
      perfusion. When systemic morphine was given together with systemic naloxone, an
      opiate antagonist, capsaicin-induced hyperaemia was restored. 5. These findings
      indicate that the capsaicin hyperaemia of vasa nervorum is locally mediated, is
      independent of central afferent connections and is sensitive to a variety of
      interventions. It requires an intact epineurial plexus that 'feeds' endoneurial
      microvessels and the release of histamine by mast cells. Its inhibition by
      morphine suggests that there are local opiate receptors on epineurial
      perivascular peptidergic fibres.

PMID- 7504728
TI  - Sodium-evoked, calcium-independent vasopressin release from rat isolated
      neurohypophysial nerve endings.
AB  - 1. The effects of Na+ on vasopressin release and on redistribution of Ca2+, Na+
      and H+ in isolated rat neurohypophysial nerve endings have been studied. 2.
      Substituting Na+ for a non-permanent cation produced a pronounced and sustained
      release of vasopressin. This increase occurred in the absence of external Ca2+
      and in nerve endings loaded with the Ca2+ chelator dimethyl-BAPTA (1,2-bis-(O
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). 3. The effect of Na+ was
      independent of a rise in intracellular Ca2+ as judged by the measurement of
      [Ca2+]i using the indicator fura-2 and 45Ca2+ efflux studies. Although Na+ could
      release Ca2+ from internal reservoirs the small elevation in [Ca2+]i induced by
      Na+ could not explain the large and sustained increase in vasopressin secretion.
      4. The channel blockers TTX (tetrodotoxin), D888 (desmethyoxyverapamil), N144 (5
      nitro-2-(phenylpropylamino)-benzoic acid) or SITS (4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulphonic acid) could not prevent the Na(+)
      dependent increase in vasopressin release. Similarly this increase was not
      affected by metabolic inhibitors (Ruthenium Red and KCN) nor by CCCP (carbonyl
      cyanide m-chlorophenylhydrazone), an uncoupler of oxidative phosphorylation. 5.
      Selectivity among monovalent cations to promote secretion was found with the
      largest effect on the secretory response being produced by Na+. Similarly Cl- was
      found to be the most potent anion studied for inducing, in the presence of Na+,
      an increase in neurohormone release. 6. Measuring [Na+]i by means of the Na+
      indicator SBFI showed that the extent of the secretory response was correlated
      with the intraterminal Na+ concentration. 7. The Na(+)-induced, Ca(2+)
      independent release of vasopressin occurred by exocytosis as judged (i) by the
      linear relationship between the amount of vasopressin secreted and that of the co
      localized neurophysin and (ii) by the demonstration that the extracellular marker
      horseradish peroxidase was only found in endocytotic vacuoles and not in the
      cytoplasm of the stimulated nerve endings. 8. The Na(+)-dependent secretory
      response found on addition of extracellular Na+ was not the result of the change
      in internal pH as measured with the indicator BCECF and as mimicked by addition
      of propionic acid. 9. Addition of Na+ to digitonin- or streptolysin-O
      permeabilized nerve endings in the presence or absence of Ca2+ also gave rise to
      an increase in vasopressin secretion. 10. It is concluded that an increase in
      internal Na+ per se can promote, in the absence of a rise in intracellular Ca2+,
      an increase in neuropeptide secretion.

PMID- 7504729
TI  - Modulation of K+ and Ca2+ channels by histamine H1-receptor stimulation in rabbit
      coronary artery cells.
AB  - 1. The modulation of whole-cell K+ and Ca2+ currents by stimulation of histamine
      H1-receptors in freshly isolated single smooth muscle cells from the rabbit
      coronary artery was characterized using the patch-clamp technique at 35 degrees
      C. Single-channel K+ currents were also analysed using the cell-attached patch
      configuration. 2. The histamine H1-receptor agonist, 2-(2-aminoethyl)pyridine
      (AEP) (0.1 mM), increased the amplitude of voltage-activated inward Ba2+
      currents, recorded using the perforated-patch recording technique, which could be
      completely blocked by the dihydropyridine antagonist, nicardipine (1 microM). 3.
      Whole-cell outward K+ currents in rabbit coronary artery cells could be
      classified into at least two components: (a) a slowly inactivating, 4
      aminopyridine (4-AP)-sensitive low-noise current, and (b) a non-inactivating,
      tetraethylammonium (TEA)-sensitive high-noise current. 4. AEP (0.1 mM) caused
      changes in whole-cell outward K+ currents which depended upon membrane voltage.
      Specifically: (a) AEP enhanced the amplitude of outward currents at voltages
      between -30 and 0 mV, and (b) AEP decreased the outward currents at more positive
      potentials. 5. The removal of extracellular Ca2+ caused little inhibition of the
      effects of AEP on K+ currents, whereas the depletion of intracellular Ca2+ stores
      by pretreatment with ryanodine and caffeine prevented the effects of AEP on K+
      channels. Moreover, acute exposure to ryanodine (10 microM) or thapsigargin (1
      microM), a Ca(2+)-ATPase inhibitor, caused voltage-dependent changes in the
      outward currents similar to those observed with AEP. These results suggest that
      the voltage-dependent effects of AEP on K+ currents are mainly mediated by
      release of Ca2+ from intracellular stores. 6. The dual stimulatory and inhibitory
      effect of AEP on whole-cell K+ currents was shown to be due to a differential
      effect on two distinct types of K+ channels. The stimulatory effect observed over
      the voltage range -30 to 0 mV was prevented by pretreatment of cells with low
      concentrations of TEA (1 mM), whereas the inhibitory effect observed at positive
      potentials was prevented by pretreatment of cells with 4-AP (3 mM). 7. Single
      channel recordings revealed two types of unitary K+ currents with conductances of
      225 and 70 pS in the cell-attached configuration with symmetrical K+ solutions
      (150 mM K+ in pipette-150 mM K+ in bath). Bath application of AEP (0.1 mM) caused
      a marked increase in the open probability of the large conductance
      channels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504731
TI  - Convective fluid flow through the paracellular system of Necturus gall-bladder
      epithelium as revealed by dextran probes.
AB  - 1. Bidirectional paracellular fluxes using radioactive dextrans as inert
      molecular probes have been measured across Necturus gall-bladder epithelium
      during conditions of normal fluid absorption. There is a net flux at all radii
      analysed (0.4-2.2 nm) in the direction of fluid absorption. 2. The net flux is
      substantial at all radii within the range. The data extraplate to 2 x 10(-6) cm s
      1 at zero probe radius, which is very close to the rate of epithelial fluid
      absorption. 3. The unstirred layers at the epithelial faces during transport have
      been determined; their contribution to the net fluxes is negligible. 4. Two
      possible mechanisms for the net flow of probes are considered: (i) that the
      probes diffuse across the junctions and are then entrained in a local osmotic
      flow along the interspaces and subepithelium; (ii) that the probes are entrained
      in volume flow across the junctions and the emergent solution subsequently passes
      through the interspaces and subepithelium. Model calculations clearly rule out
      mechanism (i) in which the maximum net flow obtainable is less than 10% of that
      observed. In addition the presence of leak paths shunting the junctions is not
      compatible with the observed fluxes. With mechanism (ii) the net flows are
      correctly predicted with all the fluid flow being transjunctional. The fluid
      absorption is therefore entirely paracellular. 5. The slope of the net flow curve
      shows no apparent change in magnitude over the range of the probe radii,
      indicating that effectively only one population of convective channels is present
      with parallel walls separated by about 7.7 nm. This agrees with the width
      previously determined by electron microscopy. 6. If the fluid absorption is
      junctional then the cellular route offers little if any relative contribution.
      The hydraulic conductivity of the junctions is not high enough, or the osmotic
      permeability of the membranes low enough, to accommodate this by osmosis and
      therefore the junctional fluid absorption must be non-osmotic.

PMID- 7504730
TI  - Selection of transmitter responses at sites of neurite contact during synapse
      formation between identified leech neurons.
AB  - 1. Pressure sensitive (P) neurons of the leech Hirudo medicinalis show both an
      inhibitory, Cl(-)-dependent response and a depolarizing, cationic response to
      pipette application of serotonin (5-HT). Serotonergic Retzius (R) neurons in
      culture reform inhibitory, Cl(-)-dependent synapses with P neurons but fail to
      elicit the extrasynaptic, depolarizing response to 5-HT. We have examined the
      localization of the selection of 5-HT responses by testing the sensitivity of P
      cell growth cones and neurites to 5-HT application. 2. As measured by
      intracellular recording at the P cell soma, synaptic release of 5-HT from R cell
      processes activated only the Cl(-)-dependent response in P cell neurites. Focal
      application of 5-HT from a micropipette depolarized uncontacted P cell growth
      cones and neurites. In contrast, processes from the same P cells that were
      contacted by R cells were rarely depolarized by 5-HT application unless the
      application pipette was moved along the neurites away from the sites of contact.
      3. The channels underlying the depolarizing response to 5-HT were identified in
      patch clamp recordings from P cell growth cones. These cation channels showed
      rare, brief openings in the absence of 5-HT. Application of 5-HT in the bath
      (outside the patch pipette) increased channel activity in uncontacted P cell
      growth cones but not in growth cones of the same P cells contacted by R cells. 4.
      We conclude that the selection of transmitter responses during synapse formation
      was localized to discrete sites of contact between the synaptic partners.

PMID- 7504732
TI  - Modulation of EPSP shape and efficacy by intrinsic membrane conductances in rat
      neocortical pyramidal neurons in vitro.
AB  - 1. Intracellular recordings were made from pyramidal neurons in layers II/III and
      V of rat visual cortical slices. Distal and proximal excitatory postsynaptic
      potentials (EPSPs) were evoked using extracellular bipolar electrodes placed on
      the slice horizontal to each cell, near the apical and basal dendrites
      respectively. Experiments were conducted in the presence of 2-amino-5
      phosphonopentanoate, picrotoxin and, in most cases, 2-hydroxy-saclofen. 2. For
      layer II/III pyramidal neurons, voltage undershoots following distal and proximal
      EPSPs (n = 7 pairs) and injected somatic pulses were rarely apparent. In layer V
      pyramidal neurons substantial voltage undershoots were recorded following distal
      and proximal EPSPs (n = 27 pairs) and injected somatic pulses, with undershoot
      being greatest for apical inputs (P = 0.001). The greater undershoots following
      apical EPSPs were also apparent in semilogarithmic plots of voltage decay where
      the slope of decay for apical EPSPs was quicker than the voltage decay following
      pulses of current injected at the soma. There was no significant difference in
      the shapes of distal and proximal EPSPs in layer II/III or layer V pyramidal
      cells under control conditions. 3. Pharmacological agents were used to reduce
      voltage undershoots. The most successful of these was alinidine, a putative
      blocker of the slow inward rectifier (IH) conductance. In the presence of bath
      applied 100 microM alinidine, undershoots were significantly reduced and it
      became possible to distinguish the relative origins of EPSPs on the basis of
      their shape. Distally generated EPSPs (n = 14) had rise times and half-widths
      that were 2.8 and 1.5 times longer respectively than those evoked proximally (n =
      10; P = 0.001 for both parameters). 4. These results confirm previous theoretical
      simulations of somatic recordings in passive model neurons where distal EPSPs
      display slower rise times and longer half-widths than proximal EPSPs. The present
      results suggest that, at least in pyramidal neurons of layer V, distal synaptic
      inputs can be specifically modulated by intrinsic membrane conductances.

PMID- 7504733
TI  - Synthesis and anti-HIV-1 activity of a series of imidazo[1,5-b]pyridazines.
AB  - A series of substituted imidazo[1,5-b]pyridazines have been prepared and tested
      for inhibitory activity against the reverse transcriptase of HIV-1 (RT) and their
      ability to inhibit the growth of infected MT-4 cells. Crystal data are reported
      on two compounds, 15c and 33. From the structure-activity relationships developed
      within this and other series, it is proposed that key features of the interaction
      with RT include hydrogen-bond acceptor and aromatic pi-orbital bonding with the
      imidazopyridazine nucleus and a benzoyl function separated from the heterocycle
      by a suitable spacer group. Exceptional activity against the reverse
      transcriptase of HIV-1 (IC50 = 0.65 nM) was obtained with a 2-imidazolyl
      substituted derivative, 7-[2-(1H-imidazol-1- yl)-5-methylimidazo-[1,5-b]pyridazin
      7-yl]-1-phenyl-1-heptanone (33) which is attributed to additional binding of the
      imidazole sp2 nitrogen atom. A number of the compounds in this series also
      inhibit the replication of HIV-1 in vitro in MT-4 and C8166 cells at levels
      observed with the nucleoside AZT.

PMID- 7504734
TI  - Nonprostanoid prostacyclin mimetics. 5. Structure-activity relationships
      associated with [3-[4-(4,5-diphenyl-2-oxazolyl)-5- oxazolyl]phenoxy]acetic acid.
AB  - cis-[3-[2-(4,5-Diphenyl-2-oxazolyl)ethenyl]phenoxy]acetic acid (3) was previously
      identified as a nonprostanoid prostacyclin (PGI2) mimetic that potently inhibits
      ADP-induced aggregation of human platelets with an IC50 of 0.18 microM. As part
      of an effort to further explore structure-activity relationships for this class
      of platelet inhibitor and to provide additional insight into the nonprostanoid
      PGI2 mimetic pharmacophore, the effect of constraining the cis-olefin moiety of 3
      into various ring systems was examined. Incorporation of the cis-olefin of 3 into
      either an oxazole (26) or an unsubstituted pyrazole (35) heterocycle provided
      compounds that are equipotent with progenitor 3. However, the oxazole 11f, which
      is isomeric with 26, inhibits ADP-induced human platelet aggregation in vitro
      with an IC50 of 0.027 microM, 6-fold more potent than 3, 26, or 35. These results
      suggest that the central oxazole ring of 11f is functioning as more than a simple
      scaffold that provides optimal stereodefinition for interaction with the PGI2
      receptor. The nitrogen atom of the central heterocycle of 11f is postulated to
      engage in hydrogen-bond formation with a donor moiety in the PGI2 receptor
      protein, an interaction not available to 26 due to the markedly different
      topology. In support of this contention, the crystal structures of 11f and 26
      contain strong intermolecular hydrogen bonds between the carboxylic acid hydrogen
      atom and the nitrogen atom of the central oxazole ring. Although 11f and 26 are
      exact isosteres and could, in principle, adopt the same molecular packing
      arrangement in the solid state, this is not the case, and the intermolecular
      hydrogen-bonding interactions in 11f and 26 are accommodated by entirely
      different molecular packing arrangements. Incorporation of the olefin moiety of 3
      into a benzene ring provided a compound, 40, over 60-fold weaker with an IC50 of
      11.1 microM. The affinities of 11f, 26, 31, 32, and 40 for the human platelet
      PGI2 receptor, determined by displacement of [3H]iloprost, correlated with
      inhibition of platelet function. The solid-state structures of 11f, 26, 31, 32,
      and 40 were determined and revealed that the more potent compounds 11f and 26
      adopt a relatively planar overall topography. In contrast, the central phenyl
      ring and the phenoxy ring of the weakly active compound 40 are rotated by 53
      degrees from planarity. The chemical shifts of the protons of the phenoxy rings
      of 3, 11f, 18, 26, 31, 32, and 40 suggest that in solution 3, 11f, 18, and 26
      adopt a planar conformation while 40 does not.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504735
TI  - Comparison of a structural and a functional epitope.
AB  - A comprehensive analysis of the energetic importance of the 31 side-chains buried
      at the interface between human growth hormone (hGH) and the extracellular binding
      domain of its receptor (hGHbp) has been carried out to assess the roles of
      contact side-chains in modulating the affinity and kinetics of binding. Each side
      chain in hGH was converted to alanine, and the kinetics and affinity were
      measured using a biosensor device. This detects binding of the mutated hormones
      to the immobilized hGHbp by changes induced in refractive index. The data
      generated on the biosensor match affinities obtained by radio-immune assay in
      solution. The study shows that only one-quarter of the side-chains buried at the
      interface can account for the majority of the binding energy. These residues
      cluster near the center of the structural epitope. The role of these side-chains
      is predominantly to slow dissociation because most of the effect of the alanine
      substitutions is to increase the off-rate, not to slow the on-rate. The hormone
      associates about 10,000 times slower than expected from random diffusion but 1000
      times faster than may be expected if one imposes strict orientation restraints
      for a productive collision. Electrostatic interactions partly modulate
      association because mutations at Arg residues most affect association and
      together contribute a factor of about 20 to the on-rate. The data suggest that
      the hormone and receptor associate by diffusion and electrostatics to form an
      ensemble of weak collisional complexes. From these a bound complex is produced
      that is stabilized by only a small proportion of the contacts. We suggest that
      solvation energies and/or side-chains interactions within the free hormone or
      receptor may be so favorable that little energy is gained at most side-chains
      upon binding. The fact that the functional binding epitope is much smaller than
      the structural epitope suggests it may be possible to design smaller hormone
      mimics.

PMID- 7504736
TI  - Crystal structure of canine and bovine granulocyte-colony stimulating factor (G
      CSF).
AB  - The crystal structures of recombinant canine and bovine granulocyte colony
      stimulating factor (G-CSF) have been determined by X-ray crystallography, using
      molecular replacement with recombinant human G-CSF as a model. G-CSF is a member
      of the cytokine family of glycoproteins that stimulate the differentiation and
      proliferation of blood cells. Human, bovine and canine G-CSF all have a molecular
      mass of about 19 kDa and share an amino acid sequence identity of about 80%. Two
      crystal forms of canine G-CSF have been solved. Form I recombinant canine G-CSF
      (rcG-CSFI; space group C2) contains one molecule in the asymmetric unit while
      form II canine G-CSF (rcG-CSFII; space group P2(1)) has two molecules in the
      asymmetric unit and bovine G-CSF (rbG-CSF; space group P2(1)2(1)2(1)) contains
      one molecule in the asymmetric unit. rcG-CSFI has been refined to an R factor of
      20.7% with data to 2.3 A resolution and rcG-CSFII has been refined to an R factor
      of 19.3% with data to 2.2 A resolution. rbG-CSF has been refined to an R factor
      of 21.3% with data to 1.7 A resolution. The structure of human, canine and bovine
      G-CSF is an antiparallel 4-alpha-helical bundle with up-up-down-down
      connectivity. With the exception of one highly exposed loop (residues 66 to 74),
      the human, canine and bovine structures are very similar to each other. Using our
      series of G-CSF crystal structures we developed a function that describes the
      probability that a particular residue position (i) contributes to a G-CSF
      receptor binding site based on two principles, (1) high sequence conservation in
      the primary sequence of human, bovine, canine and murine G-CSF and (2)
      conservation of high solvent accessibility in the human, bovine and canine
      crystal structures. On the basis of this probability function as well as a
      comparison of G-CSF to the crystal structure of human growth hormone (hGH)
      complexed with the extracellular domain of the human growth hormone receptor
      (hGHbp), residues that contribute to potential G-CSF receptor binding sites are
      identified.

PMID- 7504737
TI  - Local conformations of peptides representing the entire sequence of bovine
      pancreatic trypsin inhibitor and their roles in folding.
AB  - The conformational properties of seven overlapping peptides, 9 to 16 residues
      long, that comprise the entire primary structure of bovine pancreatic trypsin
      inhibitor (BPTI) have been characterized by circular dichroism and 1H nuclear
      magnetic resonance. The peptides are largely disordered, although apparently with
      somewhat different average conformational propensities of the polypeptide
      backbone, similar to those indicated by methods to predict secondary structure.
      Reduced BPTI appears to be approximately the sum of the individual peptides.
      Several local interactions involving aromatic rings of side-chains interacting
      with groups nearby in the primary structure have been identified and verified by
      replacing the responsible side-chains. The roles of these interactions in folding
      of reduced BPTI could be determined, as the conformational and nuclear magnetic
      resonance properties of all the major disulphide intermediates are known. Two of
      these local interactions contribute to the folding process and to stability of
      the fully folded conformation, whereas the other two do not.

PMID- 7504738
TI  - T-cell receptors from virus-specific cytotoxic T lymphocytes recognizing a single
      immunodominant nine-amino-acid viral epitope show marked diversity.
AB  - Following infection of the H-2d mouse by lymphocytic choriomeningitis virus, the
      newly generated cytotoxic T lymphocyte (CTL) response is focused to a single 9
      amino-acid peptide sequence (epitope) of the virus. More than 96% of the primary,
      secondary, and clonal CTL respond to this lymphocytic choriomeningitis virus
      nucleoprotein epitope. This unique system affords the opportunity to evaluate the
      T-cell response to a single viral CTL epitope in a case in which the outcome of
      infection, either viral clearance or host death, is mediated by the CTLs.
      Specifically, the molecular structure of the T-cell receptors (TCRs) of CTLs
      responding to this epitope was analyzed. By using an anchored polymerase chain
      reaction, the TCR chains of three CTL clones cDNAs were amplified, sequenced, and
      found to have unique V alpha of V beta chains relative to each other as well as
      to lack restriction to any particular variable chain. These data indicate that
      the highly diverse antiviral CTL response is pleomorphic and probably provides an
      advantage to the host as it limits the emergence of viral variants that could
      more easily arise if the TCR response were homogeneous.

PMID- 7504739
TI  - Apoptosis induced in CD4+ cells expressing gp160 of human immunodeficiency virus
      type 1.
AB  - In a previous study (Y. Koga, M. Sasaki, H. Yoshida, H. Wigzell, G. Kimura, and
      K. Nomoto, J. Immunol. 144:94-102, 1990), we demonstrated that the expression of
      gp160, a precursor form of envelope glycoprotein of human immunodeficiency virus
      type 1, in CD4+ cells causes the downregulation of surface CD4 and single-cell
      killing by forming intracellular gp160-CD4 complex. In the present study we
      investigated the events that lead to cell death in CD4+ cells expressing gp160.
      We found that apoptosis is induced in cells undergoing single-cell death.
      Moreover, even the cell clone, which expresses so little gp160 that it does not
      exhibit any apparent cytopathic effects, such as the inhibition of cell growth,
      was found to be highly susceptible to the apoptosis induction by the anti-Fas
      monoclonal antibody.

PMID- 7504740
TI  - Presentation of native epitopes in the V1/V2 and V3 regions of human
      immunodeficiency virus type 1 gp120 by fusion glycoproteins containing isolated
      gp120 domains.
AB  - The immune response to viral glycoproteins is often directed against conformation
      and/or glycosylation-dependent structures; synthetic peptides and bacterially
      expressed proteins are inadequate probes for the mapping of such epitopes. This
      report describes a retroviral vector system that presents such native epitopes on
      chimeric glycoproteins in which protein fragments of interest are fused to the C
      terminus of the N-terminal domain of the murine leukemia virus surface protein,
      gp70. The system was used to express two disulfide-bonded domains from gp120, the
      surface protein of human immunodeficiency virus type 1 (HIV-1), that include
      potent neutralization epitopes. The resulting fusion glycoproteins were
      synthesized at high levels and were efficiently transported and secreted. A
      fusion protein containing the HXB2 V1/V2 domain was recognized by an HIVIIIB
      infected patient serum as well as by 17 of 36 HIV-1 seropositive hemophiliac,
      homosexual male and intravenous drug user patient sera. Many of these HIV+ human
      sera reacted with V1/V2 domains from several HIV-1 clones expressed in fusion
      glycoproteins, indicating the presence of cross-reactive antibodies against
      epitopes in the V1/V2 domain. Recognition of gp(1-263):V1/V2HXB2 by the HIVIIIB
      infected human patient serum was largely blocked by synthetic peptides matching
      V1 but not V2 sequences, while recognition of this construct by a broadly cross
      reactive hemophiliac patient serum was not blocked by individual V1 or V2
      peptides or by mixtures of these peptides. A construct containing the V3 domain
      of the IIIB strain of HIV-1, gp(1-263):V3HXB2, was recognized by sera from a
      human and a chimpanzee that had been infected by HIVIIIB but not by sera from
      hemophiliac patients who had been infected with HIV-1 of MN-like V3 serotype. The
      reactive sera had significantly higher titers when assayed against gp(1
      263):V3HXB2 than when assayed against matching V3 peptides. Immunoprecipitation
      of this fusion glycoprotein by the human serum was only partially blocked by V3
      peptide, indicating that this infected individual produced antibodies against
      epitopes in V3 that were expressed on the fusion glycoprotein but not by
      synthetic peptides. These data demonstrated that the chimeric glycoproteins
      described here effectively present native epitopes present in the V1/V2 and V3
      domains of gp120 and provide efficient methods for detection of antibodies
      directed against native epitopes in these regions and for characterization of
      such epitopes.

PMID- 7504743
TI  - Urologists on a tightrope: coping with a changing economy.

PMID- 7504741
TI  - Probing the structure of the human immunodeficiency virus surface glycoprotein
      gp120 with a panel of monoclonal antibodies.
AB  - We have probed the structures of monomeric and oligomeric gp120 glycoproteins
      from the LAI isolate of human immunodeficiency virus type 1 (HIV-1) with a panel
      of monoclonal antibodies (MAbs); most of these MAbs are directed against
      continuous epitopes. On native monomeric gp120, most of the first conserved (C1)
      domain is accessible to MAbs, although some regions of C1 are relatively
      inaccessible. All of the MAbs directed against the C2, C3, and C5 domains bind
      preferentially to denatured monomeric gp120, indicating that these regions of
      gp120 are poorly accessible on the native monomer, although the extreme C
      terminus in C5 is well exposed. Segments of the V1, V2, and V3 loops are exposed
      on the surface of monomeric gp120, although the base of the V3 loop is
      inaccessible. A portion of C4 is also available for MAb binding on monomeric
      gp120, as is the extreme C terminus in C5. However, on oligomeric gp120-gp41
      complexes, only the V2 and V3 loops (and perhaps V1) are well exposed and a
      segment of the C4 region is partially exposed; continuous epitopes in C1 and C5
      that are accessible to antibodies on monomeric gp120 are occluded on the
      oligomer. Although deletion of the V1, V2, and V3 loops resulted in increased
      exposure of several discontinuous epitopes overlapping the CD4-binding site, the
      exposure of most continuous epitopes on the monomeric gp120 glycoprotein was not
      affected. These results imply a HIV-1 gp120 structure in which the conserved
      continuous determinants are inaccessible; in some cases, this inaccessibility is
      due to intramolecular interactions between conserved regions, and in other cases,
      it is due to intermolecular interactions with other components of the
      glycoprotein spike. These findings have implications for the design of subunit
      vaccines based on gp120.

PMID- 7504742
TI  - Reverse transcription in hepatitis B viruses is primed by a tyrosine residue of
      the polymerase.
AB  - All known DNA polymerases require primers for the initiation of DNA synthesis.
      While cellular polymerases and reverse transcriptases use free hydroxyl groups of
      RNA or DNA, the DNA polymerases of certain animal viruses and bacteriophages
      depend upon hydroxyl groups of amino acid residues within proteins as primers for
      DNA synthesis. Recently, the reverse transcriptase of a hepadnavirus has been
      shown to prime RNA-directed DNA synthesis from an internal site of the
      polypeptide (G.H. Wang and C. Seeger, Cell 71:663-670, 1992). In this report we
      demonstrate that a tyrosine residue of the polymerase polypeptide is the site of
      a phosphodiester linkage with the first nucleotide of minus-strand DNA. This
      tyrosine residue is located within an amino-terminal domain of the polymerase
      polypeptide and is indispensable for the priming of reverse transcription. Our
      results demonstrate that the hepatitis B virus reverse transcriptase can initiate
      DNA synthesis without the requirement for tRNA as a primer.

PMID- 7504744
TI  - Prostate cancer.

PMID- 7504746
TI  - Management of benign prostatic hyperplasia by transurethral laser ablation in
      patients treated with warfarin anticoagulation.
AB  - Transurethral laser ablation of the prostate gland was used to treat benign
      prostatic hyperplasia in 10 patients on warfarin anticoagulant therapy who had
      either significant clinical symptoms or who were in urinary retention.
      Anticoagulant therapy did not require alteration at any stage during treatment.
      All patients noticed improvements in symptom score assessments, flow rates and
      residual urine volumes following this procedure, and no significant complications
      were encountered. The hemostatic nature of neodymium:YAG laser energy as applied
      in this procedure appears to result in a technical improvement upon conventional
      transurethral resection for the treatment of symptomatic benign prostatic
      hyperplasia in patients taking warfarin anticoagulant therapy.

PMID- 7504745
TI  - Nitric oxide mediates penile erection in cats.
AB  - The present study was undertaken to investigate the in vivo effects of nitric
      oxide (NO) mediating agents injected intracavernosally on penile erection in
      cats. All NO donors increased the cavernosal pressure and penile length in a dose
      dependent manner. The maximal effects on cavernosal pressure and penile length
      induced by s-nitrosocysteine (NO-CYS) and s-nitroso-n-acetylpenicillamine (SNAP),
      respectively, were 8-fold and 5-fold increases in pressure, and 45% and 34%
      increases in length when compared with baseline values. These changes were
      comparable to that caused by the control drug combination (papaverine,
      phentolamine and prostaglandin E1). The effects of acetylcholine (ACh) and
      substance P on cavernosal pressure and penile length were less than those
      obtained with the control drug combination, NO-CYS (p < 0.01), or SNAP (p <
      0.05). N omega-nitro-l-arginine-methyl-ester (L-NAME), a nitric oxide synthase
      (NOS) inhibitor, significantly decreased the effects of NO-CYS, ACh and substance
      P on penile erection. This in vivo study with NO donors and an NOS inhibitor
      suggests that NO is a mediator of penile erection in cats.

PMID- 7504747
TI  - Urinary prostate specific antigen levels after radical prostatectomy.
AB  - It was recently demonstrated that urinary prostate specific antigen (PSA) is
      discordant with serum PSA in many patients after radical prostatectomy. This
      observation led to the speculation that elevated urinary PSA in the face of
      undetectable serum PSA may indicate early disease recurrence. We measured urinary
      PSA levels in 30 patients who had undergone radical prostatectomy for prostate
      carcinoma and 7 patients who had undergone cystoprostatectomy for bladder cancer.
      PSA levels of randomly collected urine samples ranged from 0.00 to 22.9 ng./ml.
      and 0.01 to 8.37 ng./ml., respectively. There was no correlation among urinary
      and serum PSA levels, pathological stage or type of operation. In 14 patients who
      had undergone radical prostatectomy and who had measurable levels of urinary PSA
      voided specimens were divided into initial stream and end stream voided samples.
      The PSA levels in the end stream voided samples were significantly less than the
      initial stream sample in 12 of the 14 patients. In men who had undergone radical
      prostatectomy urethral swab samples were analyzed for PSA. Of 26 patients 24 had
      detectable levels of urethral swab PSA (range 0.01 to 39.04 ng./ml., median 0.93
      ng./ml.). Urethral swab PSA levels did not correlate with serum PSA values or
      pathological stage of disease. Of 7 patients who had defunctionalized urethras
      after radical cystoprostatectomy 5 had significantly elevated PSA in the urethral
      wash or swab samples (range 4.3 to 24.5 ng./ml.). Immunohistochemical analysis of
      urethrectomy specimens demonstrated positive staining for PSA in 3 of 4
      specimens. We conclude that the major source of urinary PSA following total
      prostatectomy is the urethra itself rather than residual prostate tissue.
      Measuring serial urinary PSA appears to have limited value in monitoring patients
      after radical prostatectomy. Whether this urethral PSA can ever contaminate the
      serum levels of PSA after radical prostatectomy is currently under investigation.

PMID- 7504748
TI  - The use of prostate specific antigen and prostate specific antigen density in the
      diagnosis of prostate cancer in a community based urology practice.
AB  - Since 1989 we have used serum prostate specific antigen (PSA) levels as an
      indication for ultrasound guided systematic biopsies of the prostate. Realizing
      that the PSA level in part reflects prostatic glandular epithelial volume, we
      reviewed the accumulated data on our last 2,340 biopsies to determine if the
      quotient of PSA and prostatic volume, prostate specific antigen density, provided
      any further diagnostic information. There were evaluable data for 2,020 patients.
      Prostate specific antigen density levels are shown to have a strong correlation
      with the diagnosis of prostate cancer and provide a more reliable indication for
      ultrasound guided biopsy of the prostate than PSA alone.

PMID- 7504749
TI  - Measurement of serum prostate specific antigen using IMx prostate specific
      antigen assay.
AB  - The analytical characteristics of singlet determinations of the IMx prostate
      specific antigen (PSA)  assay are similar to the mean of duplicates using the
      Tandem-R not equal to PSA assay. The 2 assays are standardized equally and
      provide test results that correlate well (r = 0.9997). The IMx PSA assay is more
      automated, requires less technologist time and provides faster test results. This
      assay has a minimal detection limit of 0.02 to 0.04 ng./ml. and functional
      sensitivity at a 20% coefficient of variation of 0.06 to 0.13 ng./ml. With a
      sensitive lot of IMx PSA reagents, only 38% of post-radical prostatectomy
      patients had nondetectable values compared to 60% with the Tandem-R PSA assay.
      The within-person, biological standard deviation of PSA concentrations in post
      radical prostatectomy patients was 0.01 ng./ml. Therefore, with a sensitive assay
      these low concentration measurements should be reliable for monitoring. However,
      the clinical use of these low concentrations for early detection of tumor
      recurrence must await further studies.

PMID- 7504750
TI  - Systematic sextant biopsies in 651 patients referred for prostate evaluation.
AB  - In 651 patients mapping of the prostate by 6 systematic sextant ultrasonography
      guided biopsies was performed without major side effects using the automatic
      biopsy gun. The histological findings provided data on patients with normal and
      abnormal prostates as determined by digital rectal examination. Only 3 of 72
      nonurological patients (4%) with normal prostate specific antigen (PSA) levels of
      less than 4 ng./ml. had prostate cancer. Of the 259 patients with a firm prostate
      on digital rectal examination 105 (41%) had prostate cancer. For those with a PSA
      level of less than 4 and 4 ng./ml. or greater the positive biopsy rates were 13%
      and 58%, respectively. Of 56 patients with clinical stage B or C disease and a
      PSA level of less than 4 ng./ml. 20 (36%) had prostate cancer, compared to 155 of
      187 (83%) with a PSA level of 4 ng./ml. or greater. Transrectal ultrasound was
      not helpful in screening for prostate cancer due to the low positive biopsy rate
      for hypoechoic lesions. However, among 175 patients with clinical stage B or C
      disease transrectal ultrasound identified 157 (90%) with prostate cancer.

PMID- 7504751
TI  - [CD14-positive and nonspecific esterase-positive neutrophils in a patient with
      refractory anemia with excess of blasts in transformation].
AB  - A 34-year-old man was admitted with lumbago and anemia in November 1992.
      Hematological examination revealed an Hb 9.2g/dl, WBC count 13,500 microliters
      (33% blasts), and monocyte count 3,400/microliters. Bone marrow examination
      showed hyperplasia with dysplasia in trilineage blood cells and increased blasts
      (21.8%). A diagnosis of refractory anemia with excess of blasts in transformation
      (RAEB in T) was made. Cytochemical examination revealed the neutrophils in the
      peripheral blood were 66.5% positive for alpha-naphthyl butyrate esterase
      inhibited by sodium fluoride, 4.0% positive for peroxidase and 75% positive for
      alkaline phosphatase. The results of immuno-alkaline phosphatase stainings
      (avidin biotin alkaline phosphatase complex method) of neutrophils were as
      follows; CD16 (94.5%), CD24 (91.0%), CD13 (93.0%), CD14 (52.5%), CD33 (39.0%),
      CD36 (16.5%), HLA-DR (17.0%). These neutrophils exhibited monocyte-specific
      features and failed to show characteristics of neutrophils.

PMID- 7504752
TI  - [Streptomycin-induced severe aplastic anemia successfully treated with high-dose
      methylprednisolone pulse therapy and rhG-CSF].
AB  - An 83-year-old male was admitted with pulmonary tuberculosis. He was started on
      rifampicin, isoniazid, and streptomycin (SM). The hematological data at 12 weeks
      after the treatment showed pancytopenia (RBC: 2.14 x 10(6)/microliters, Hb:
      7.2g/dl, Plt: 1.8 x 10(4)/microliters, WBC: 700/microliters). All the above
      medicines were discontinued and he received bolus methylprednisolone (bmPSL) and
      recombinant human granulocyte-colony stimulating factor (rhG-CSF). After 3 cycles
      of bmPSL, red blood cells and platelets gradually increased. White blood cells
      also increased in response to rhG-CSF. Bone marrow aspirate and biopsy specimens
      showed normocellularity, indicating recovery from aplastic anemia. Drug
      lymphocyte stimulation test was positive for SM.

PMID- 7504753
TI  - [Relationship of an extracellular matrix protein, tenascin and breast diseases].
AB  - Tenascin is an extracellular matrix glycoprotein consisting of six disulfide
      linked subunits with molecular masses of 190-250 kDa. Molecular analysis of the
      tenascin gene revealed that it contains a region homologous to epidermal growth
      factor genes, repetitive sequences of the type III fibronectin and the fibrinogen
      gene. Culture studies have shown that tenascin has multiple functions including
      cell attachment and detachment, promotion and inhibition of neural crest cell
      migration, cell growth stimulation and hemagglutination. Immunohistochemically,
      tenascin shows a characteristic and spatially restricted distribution. In mouse
      mammary glands, tenascin protein is demonstrated in the dense mesenchyme present
      around growing epithelia during embryogenesis and oncogenesis. Tenascin is
      expressed in normal human adult breast tissue and benign conditions, although it
      is expressed more abundantly in breast cancer tissue. Prominent tenascin staining
      is found in dense cancer-mesenchymal junctions. The staining positivity is
      significantly correlated with metastasis to regional lymph nodes and tumor grade.
      Tenascin positive patients have a significantly poorer prognosis compared with
      tenascin-negative patients. Although the biological functions of tenascin in
      breast cancer tissue have not yet been clearly elucidated, tenascin staining in
      surgical tissue specimens might be useful when applied to detect a subgroup of
      breast cancer patients who have a poorer prognosis.

PMID- 7504754
TI  - [Clinical evaluation of a lung cancer-associated protein antigen, cytokeratin 19
      fragment: I. Radioimmunoassay and its fundamental character for clinical
      laboratory measurement].
AB  - Serum level of cytokeratin 19 fragment; which is a tumor associated antigen of
      lung cancer; was detected by the radioimmunometric assay. Reliability for
      clinical laboratory measurement was investigated. Detective range of cytokeratin
      19 fragment was 0-50 ng/ml and the results including reproducibility, linearity
      of the data from diluted standard samples, was good enough for laboratory
      practice use. Although, influence of high concentration of CA19-9 over
      cytokeratin 19 fragment assay was suspected, there was no correlation between
      amount of added the antigen to data of cytokeratin 19 fragment. So direct cross
      reactivity of cytokeratin 19 fragment antibody to CA19-9 seemed less possible. As
      inhibitory effect of samples which contained over 100 ng/ml of cytokeratin 19
      fragment on assay was observed due to antigen excess, evaluation by diluted
      sample was necessary for the samples that showed over detective limit.

PMID- 7504755
TI  - [Immunocytohistochemical studies of AFP producing gastric cancer--cytomorphology
      and characteristics of AFP positive cells].
AB  - In 24 cases (5.5%) out of 438 cases of gastric cancer showing serum AFP over 20
      ng/ml, 14 cases (3.2%) showed AFP positive reaction in cancer cells by
      immunostaining. AFP localization in cancer cells classified into marginal type,
      granular type, diffuse type and inclusion type. Mixed combination of these types
      increased in high serum AFP level. Cytomorphology of AFP positive cells was
      classified to clear cell type, hepatoid cell type and round cell type. Clear cell
      type showed endodermal sinus like pattern in histomorphology. Clear cell type and
      hepatoid cell type were mixed, and transient. These types showed eosinophilic
      hyaline like globules, poor mucin production, and rich glycogen in cytoplasm. By
      immunohistochemistry showed positive rate in HCG:21.4%, PLAL:50. 0%, SP1:50.0%,
      CK:14.3% and alpha 1-AT:92.9%, and recognized reaction of germ cell tumor
      (endodermal sinus tumor) marker. We thought AFP producing gastric cancer
      suggested differentiation to germ cell tumor (endodermal sinus tumor). The AFP
      positively stained cases were found in a high age group with advanced cancer
      located pylorus to corpus, medullary growth pattern, and high rate in liver
      metastases.

PMID- 7504756
TI  - [Palliative radiotherapy for bone pain in hormone refractory prostate cancer].
AB  - From 1970 to 1992, 23 patients were treated with irradiation for palliation of
      pain caused by bone metastases from hormone refractory adenocarcinoma of the
      prostate at Cancer Institute Hospital. External beam irradiation was delivered to
      painful bony metastatic sites using linear accelerator. Numbers of irradiated
      sites were 1, 2, 3 in 6 patients, 4 in 3 patients and 5 or 7 in one patient. To
      evaluate the pain relief at the irradiated sites, severity and frequency of pain
      were measured quantitatively before and 1 month after the treatment. Overall
      efficacy of palliation was evaluated by summing up results of the irradiated
      sites in each patient. Pain relief was obtained in all the irradiated sites.
      Minimal relief, partial relief and complete relief of pain were achieved in 10%,
      15% and 75% of the 60 irradiated sites, respectively. No significant dose
      response relationship was observed. Complete pain relief was attained less
      frequently at the sites with severe and constant pain that those with moderate
      and intermittent pain. Minimal, partial and complete palliation of pain was
      attained in 9%, 17% and 74% of 23 patients, respectively. In patients with highly
      extensive bone metastases, many irradiated sites, or many irradiated bones,
      complete palliation was difficult to obtain. Recurrence of pain was observed in
      one site. In other 59 irradiated sites, pain relief lasted until patient's death
      or throughout the follow-up period (maximum 51 months, median 9 months). We
      concluded that external beam irradiation is an effective palliation therapy for
      pain of bone metastases from hormone refractory prostate cancer and will play a
      considerable role in the management of advanced disease.

PMID- 7504757
TI  - [Effect of benign prostatic hypertrophy on the endothelin-1 receptor density in
      human urinary bladder and prostate].
AB  - We measured the amount of binding sites for endothelin-1 (ET-1) in the bladder
      and prostate in patients with and without benign prostatic hypertrophy (PH and
      NPH group) using 125I-ET-1. Also the localization of ET-1 binding sites in
      hypertrophied adenoma was studied using autoradiography. Saturation experiments
      with 125I-ET-1 revealed that there were single class of saturable high affinity
      binding sites for 125I-ET-1 in the homogenate of the bladder (dome and base) and
      prostate (adenoma and capsule). The KD values to the bladder and prostate were
      not different between PH and NPH group. The Bmax values in the bladder (base and
      dome) were significantly lower in the PH group. While those in the prostate
      (adenoma and capsule) were significantly higher in the PH group. Autoradiograms
      of hypertrophied adenoma showed that ET-1 binding sites were localized to the
      stromal smooth muscles as well as to the glandular epithelium. These data suggest
      that ETs affect the pathophysiology of BPH through the changes in receptor
      density in both the bladder and prostate.

PMID- 7504758
TI  - [Blood level monitoring of FK506 on kidney transplant recipients].
AB  - Blood level monitoring of FK506 was performed on 6 kidney transplant recipients.
      Reproducibility was evaluated on trough and AUC levels in both whole blood and
      plasma samples. Reproducibility was almost the same degree on both trough and AUC
      levels and in both whole blood and plasma samples. Trough and AUC levels in whole
      blood and AUC in plasma were low at the onset of rejection episodes, whereas
      those were high at the onset of adverse effects by FK506 such as hyperglycemia,
      hyperkalemia and neurological symptoms. Frequent trough level monitoring is
      useful to detect kidney transplant rejection and adverse effects by FK506.

PMID- 7504759
TI  - Introduction. Why nitric oxide donors?

PMID- 7504760
TI  - Introduction to EDRF research.
AB  - In response to acetylcholine, endothelial cells were shown to release a
      nonprostanoid factor, called endothelium-derived relaxing factor (EDRF), which
      caused relaxation of vascular smooth muscle. Since this discovery in 1980, many
      additional agents have been shown to stimulate release of EDRF from endothelium.
      Biological and chemical evidence has supported the proposal that EDRF is nitric
      oxide (NO), a potent vasodilator. Research on the synthesis, inhibition, and
      physiological roles of EDRF/NO has led to studies of this factor in vascular
      regulation and in various disease states, including hypertension,
      atherosclerosis, and diabetes.

PMID- 7504761
TI  - Nitric Oxide Donors and the Treatment of Cardiovascular Disease. Proceedings of a
      symposium. New Orleans, Louisiana, November 15, 1992.

PMID- 7504762
TI  - The sydnonimine C87-3754 evokes endothelium-independent relaxations and prevents
      endothelium-dependent contractions in blood vessels of the dog.
AB  - Experiments were designed to compare the relaxing activities of the new
      sydnonimine C87-3754 with SIN-1 in arteries and veins of the dog, and to
      determine whether C87-3754 can prevent endothelium-dependent contractions. Rings
      of coronary and femoral arteries, and saphenous veins were suspended in organ
      chambers for the measurement of changes in isometric tension. SIN-1 and C87-3754
      evoked concentration-dependent relaxations in all rings of blood vessels
      contracted with a submaximal concentration of either prostaglandin F2 alpha,
      endothelin-1, phenylephrine, or norepinephrine. In both arteries and veins, the
      concentration-relaxation curves to C87-3754 were shifted significantly to the
      right (by two to three logarithmic units) of that to SIN-1. The presence of
      endothelium significantly inhibited the relaxations to SIN-1 but did not affect
      those to C87-3754. The treatment of coronary arteries with methylene blue or
      oxyhemoglobin significantly impaired the relaxation to SIN-1 and C87-3754.
      Neither C87-3754 nor its prodrug pirsidomine (CAS 936) affected the membrane
      potential in coronary arteries. The endothelium-dependent contractions evoked by
      nitro L-arginine, arachidonic acid, and the calcium ionophore A23187 in basilar
      arteries of the dog were inhibited by C87-3754. These results indicate that the
      sydnonimine C87-3754 is a dilator of both arterial and venous smooth muscle, and
      can prevent endothelium-mediated contractions in cerebral arteries of the dog.
      The inhibition of vascular tone is likely to involve the activation of soluble
      guanylate cyclase, causing enhanced production of cyclic guanosine monophosphate
      in the smooth muscle without a change in membrane potential.

PMID- 7504763
TI  - The role of NO release in the control of large and small coronary artery tone in
      conscious dogs.
AB  - Intravenous administration of the nitric oxide donor CAS 754 (10-100
      micrograms/kg) elicited a long-lasting, highly selective, and dose-dependent
      increase in large epicardial coronary diameter in conscious dogs, whereas
      nitroglycerin (up to 0.3 micrograms/kg) induced a shorter and less selective
      dilation of the large conductance vessels. In contrast, acetylcholine
      simultaneously increased large epicardial coronary artery diameter and decreased
      coronary resistance, regardless of the doses administered (0.01-3 micrograms/kg).
      Three days after endothelium removal by limited coronary angioplasty, the
      vasodilator effects of acetylcholine and reactive hyperemia were suppressed,
      whereas those induced by CAS 754 and nitroglycerin were not significantly
      different from those observed before endothelium removal. These data show that
      the epicardial coronary vasodilator effects of both CAS 754 and nitroglycerin are
      endothelium-independent in vivo. Thus, the unique pharmacological profile of CAS
      754 on coronary dynamics could prove to be of major importance in the treatment
      of angina pectoris.

PMID- 7504764
TI  - Effectiveness of an NO-releasing pirsidomine derivative on coronary conductance
      during long-term administration.
AB  - Nitrovasodilators have long been used in the treatment of myocardial ischemia.
      One of the limitations of their chronic administration is loss of drug action
      over time. Nitrovasodilator-induced drug tolerance results from either the loss
      of cyclic guanosine monophosphate-dependent dilator effects, or from biological
      counterregulatory processes, usually neurohormonal adaptations. C87-3754, a
      derivative of pirsidomine, is a new nitric oxide-releasing sydnonimine.
      Continuous 5-day infusion of C87-3754 in dogs did not result in a substantial
      loss of drug action. There was long-lasting dilation evident in the large
      coronary arteries and venous bed, resulting in improved coronary conductance.
      Administration of C87-3754 was associated with reduction in cardiac preload, wall
      stress, and subendocardial tissue pressure.

PMID- 7504765
TI  - Protection of ischemia-reperfusion injury by sydnonimine NO donors via inhibition
      of neutrophil-endothelium interaction.
AB  - Ischemia of a vascular bed followed by reestablishment of blood flow results in
      an accelerated and severe form of tissue injury known as "reperfusion injury." We
      have investigated reperfusion injury in cats subjected to either myocardial
      ischemia-reperfusion or splanchnic ischemia-reperfusion. In both cases, a
      critical early event after reperfusion is endothelial dysfunction characterized
      by reduced release of endothelium-derived relaxing factor now known to be nitric
      oxide (NO). Endothelial dysfunction leads to adherence of polymorphonuclear (PMN)
      leukocytes to the dysfunctional endothelium. Infusion of a sydnonimine NO donor
      (C87-3754), but not a similar compound lacking the NO moiety (C88-3934), just
      before reperfusion protected in both forms of ischemia-reperfusion. In the first
      case, C87-3754, but not C88-3934, attenuated myocardial necrosis, and in the
      second case, the NO donor improved survival and moderated the indices of shock.
      In both cases, C87-3754 preserved the endothelium of the ischemic-reperfused
      vasculature and exerted anti-PMN effects (i.e., reduced PMN adherence to the
      endothelium or attenuated PMN release of superoxide radicals). Thus, an NO donor
      infused at a rate calculated to replace the lost NO from the vascular endothelium
      of the ischemic region exerts significant protective effects on reperfusion of
      that ischemic vascular bed.

PMID- 7504766
TI  - Nitric oxide/nucleophile complexes: a unique class of nitric oxide-based
      vasodilators.
AB  - Complexes of nitric oxide (NO) with nucleophiles, also known as nitric
      oxide/nucleophile adducts or NONOates, appear to offer many advantages as
      research tools in cardiovascular pharmacology and may have future clinical
      potential as well. A wide variety of NONOates can be synthesized simply by
      exposing various nucleophilic compounds to NO. The products are generally stable
      as solids and highly soluble in aqueous media. The potent vasodilator activity
      displayed by select members of this series is endothelium independent and is
      mediated by the free NO that is released on dissolution, which activates smooth
      muscle guanylate cyclase with subsequent intracellular cyclic guanosine
      monophosphate production. NO release from the NONOate complexes is not catalyzed
      by exogenous thiol or albumin. The NONOates differ from other currently available
      nitrovasodilators in that their potency as vasorelaxants correlates closely with
      data on their first-order rates of spontaneous reversion to NO in simple aqueous
      buffers. The compounds' properties can be conveniently altered by changing the
      identity of the nucleophilic residue. Continued work with NONOate complexes may
      provide useful clinical agents as well as improved tools for probing the
      bioregulatory roles of NO.

PMID- 7504767
TI  - Endothelial and myocardial cell protection by a cysteine-containing nitric oxide
      donor after myocardial ischemia and reperfusion.
AB  - The cardioprotective actions of SPM-5185, a novel cysteine-containing nitric
      oxide (NO) donor, were investigated in two models of myocardial ischemia
      reperfusion (MI-R) injury. In the first study, dogs were subjected to 60 min of
      left anterior descending (LAD) coronary artery occlusion followed by 270 min of
      reperfusion. During reperfusion, animals were randomly assigned to receive
      intracoronary SPM-5185 (500 nM) or the NO-deficient analogue of SPM-5185, SPM
      5267 (500 nM). Transmural myocardial blood flow to the ischemic zone was not
      different between the SPM-5185 group of dogs and the SPM-5267 group (0.04 +/-
      0.01 and 0.03 +/- 0.01 ml/min/g, respectively). Similarly, the area of left
      ventricular myocardium placed at risk by LAD coronary artery occlusion was
      equivalent in dogs receiving SPM-5185 (33.6 +/- 3%) and SPM-5267 (30.4 +/- 2%).
      However, the necrotic area, expressed as a percentage of the area at risk, was
      reduced by 70% in the SPM-5185-treated dogs (14.5 +/- 4 vs. 47.5 +/- 9%; p <
      0.001). Furthermore, cardiac myeloperoxidase activity indicated that fewer
      neutrophils accumulated in the necrotic zone of the SPM-5185-treated dogs. In the
      second study, dogs were subjected to 30 min of global myocardial ischemia
      followed by 1 h of cardioplegic arrest and 1 h of reperfusion. SPM-5185 (10
      microM) added to the blood cardioplegia solution resulted in a 95 +/- 14% post
      ischemic recovery of contractile function compared with 36 +/- 8% (p < 0.05) in
      vehicle-treated dogs. Additionally, SPM-5185 treatment completely preserved
      coronary arterial vasorelaxation to acetylcholine after ischemia and reperfusion
      and resulted in a 62% reduction in cardiac tissue myeloperoxidase activity (p <
      0.05). We conclude that (a) SPM-5185 exerts significant cardioprotection from MI
      R injury after regional or global ischemia, and (b) this cardioprotection appears
      to be related to the inhibition of neutrophil-mediated injury.

PMID- 7504768
TI  - Pirsidomine, a novel nitric oxide donor, suppresses ischemic arrhythmias in
      anesthetized pigs.
AB  - The hemodynamic profile and antiarrhythmic properties of pirsidomine, a nitric
      oxide donor, were examined in pigs. Intravenous administration of pirsidomine (1
      mg/kg) to chloralose-anesthetized open-chest pigs resulted in a decreased
      afterload, and a reduced myocardial contractility and myocardial oxygen
      consumption (assessed by rate-pressure product), with no alterations in heart
      rate. After induction of regional myocardial ischemia by occlusion of the left
      anterior descending coronary artery, pigs given pirsidomine experienced fewer
      ventricular ectopic beats (119 +/- 29) than control animals did (217 +/- 53; p <
      0.05), seen primarily as a reduction in the number of couplets and triplets.
      Although the incidence of ventricular fibrillation was unaffected by pirsidomine,
      the time to onset of this arrhythmia was significantly prolonged by this
      intervention (21.3 +/- 0.9 min versus 16.1 +/- 2.5 min in controls; p < 0.05).
      Furthermore, the ST-segment depression seen throughout the 30-min occlusion
      period in controls was not sustained beyond 5 min postocclusion in pirsidomine
      treated pigs. Taken together, and in the absence of an ex vivo antiplatelet
      effect with this dose of pirsidomine, these results suggest that the
      antiarrhythmic effect of pirsidomine lies in its hemodynamic effects, resulting
      in a reduction of ischemia. The ex vivo effect of pirsidomine on free radical
      generation from isolated leukocytes was also investigated. Luminol-enhanced
      chemiluminescence produced by leukocytes in response to phorbol myristate acetate
      was markedly depressed in cells isolated from blood withdrawn after
      administration of pirsidomine, compared with cells tested before drug
      administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504769
TI  - Effects of an orally active NO-releasing agent, CAS 936, and its active
      metabolite, 3754, on cardiac and coronary dynamics in normal conscious dogs and
      after pacing-induced heart failure.
AB  - The mechanism of action of nitrates, compounds that have been used classically in
      the treatment of heart failure, appears to be the stimulation of guanylate
      cyclase in vascular smooth muscle, perhaps the same physiologic action as
      endothelium-derived relaxing factor, now thought to be synonymous with nitric
      oxide (NO). Drugs that release NO either inside cells or in plasma have been
      developed recently. One such compound, CAS 936, when taken orally, is converted
      to an active metabolite, 3754. The goal of our studies was to determine the
      effects of CAS 936 and 3754 on cardiovascular function in conscious dogs before
      and after the development of pacing-induced heart failure. CAS 936 (10 mg/kg,
      p.o.) increased large coronary artery diameter 9.1 +/- 1.2% and reduced left
      ventricular end diastolic pressure (LVEDP) 2.5 +/- 0.5 mm Hg, but had no
      significant effects on coronary blood flow or vascular resistance. The metabolite
      3754 caused dose-related increases in coronary artery diameter, and large
      reductions in LVEDP. The effect of these compounds on large coronary artery
      diameter was significantly greater (p < 0.05) than that of nitroglycerin (25
      micrograms/kg). After heart failure, both CAS 936 and 3754 caused significant
      increases in large coronary artery diameter (10%) and a reduction in preload, up
      to 10 mm Hg, which was even larger than in normal dogs. Thus, these NO-releasing
      agents are potent selective large-vessel dilators that also reduce preload and
      maintain this unique vasodilator profile even in the failing heart.

PMID- 7504770
TI  - Expression of mRNA for serglycin core protein and other platelet alpha granule
      proteins is increased in human erythroleukemia cells by phorbol myristate
      acetate.
AB  - This study has determined the effects of phorbol-12-myristate-13-acetate (PMA)
      and dimethylsulfoxide (DMSO) on mRNA levels for the serglycin proteoglycan core
      protein in human erythroleukemia (HEL) cells. We have compared these changes to
      those for mRNA for other proteins which are known to be synthesized by HEL cells
      and megakaryocytes and are known to be localized to alpha granules within
      platelets. PMA caused a large increase in mRNA for serglycin within two hours of
      treatment of the cells, and the increase persisted for at least 72 hours. DMSO
      did not cause a significant change in mRNA levels. mRNA for platelet factor 4,
      transforming growth factor-beta, and P-Selectin (PADGEM, GMP-140) were also
      increased by PMA treatment. The mRNA for platelet factor 4 was substantially
      reduced in the presence of DMSO. The increase of mRNA for serglycin induced by
      PMA was consistent with our previous observation that synthesis of proteoglycans
      from [35S]sulfate was greatly stimulated by PMA in HEL cells. The data suggest
      that up-regulation of synthesis of proteoglycans is induced by PMA in cells which
      have the capacity to differentiate along the megakaryocytic lineage, as opposed
      to cell lines such as HL-60 in which proteoglycan synthesis is reduced in the
      presence of this differentiation-inducing agent.

PMID- 7504771
TI  - Transient expression of the tartrate-resistant acid phosphatase (TRAP) gene in
      hamster cells: a pilot study.
AB  - Tartrate-resistant acid phosphatase (TRAP) became known as the characteristic,
      albeit not specific, marker enzyme for hairy cell leukemia (HCL). It is also
      expressed in other types of leukemic cells and in a variety of normal
      hematopoietic cells under both physiological and artificial conditions. The role
      of this distinctive enzyme is still unknown. TRAP hydrolyzes several chemical
      compounds, but its physiological substrate remains to be elucidated. Here, the
      insertion of a human TRAP cDNA into mammalian expression vector pSBC-2 yielded a
      construct that encoded enzymatically active TRAP in transfected baby hamster
      kidney cells (BHK-21). TRAP was expressed transiently, as shown by Northern blot
      analysis, polyacrylamide gel electrophoresis, isoelectric focusing and
      cytochemical staining. BHK-21 cells over-expressing the enzyme had a growth rate
      that was approximately 50% of that observed in control cells. A stable expression
      could not be achieved. Recent evidence suggested that TRAP might function as a
      protein tyrosine phosphatase. The effect of TRAP on protein tyrosine
      phosphorylation was examined by immunoblotting with an anti-phosphotyrosine
      monoclonal antibody (MoAb). The level of tyrosine phosphorylation was clearly
      lower in transfected BHK-21-TRAP cells than in the control cultures. Phorbol
      ester-mediated induction of protein tyrosine phosphorylation could overcome the
      status of reduced phosphorylation in BHK-21-TRAP cells. Furthermore, upon
      treatment with 12-O-tetra-decanoylphorphol-13-acetate tyrosine phosphorylation
      reached similar levels to stimulated control cells, indicating the existence of a
      functional endogenous phosphorylation network. Thus, TRAP might function as an
      antagonistic counterpart of cellular protein tyrosine kinases and could be
      involved in the control of cellular activation, proliferation, and
      differentiation.

PMID- 7504772
TI  - Expression of NK and lymphoid-associated antigens in blast cells of acute
      myeloblastic leukemia.
AB  - In the present study, the expression of two NK-associated antigens (CD56 and
      CD16) together with six 'classically' considered lymphoid-related markers
      (TDT,CD19,CD10,CD7,CD2,CD4) has been analyzed by appropriate dual combinations in
      265 acute myelogenous leukemia (AML) patients. Among the lymphoid markers, CD4
      and CD7 were those most frequently expressed by AML blast cells (58% and 21.6%,
      respectively) while the incidence of positivity for the other markers was lower:
      CD19 (7.8%), CD10 (10.9%), CD2 (11.4%), and TDT (11.3%). Regarding NK-associated
      antigens, CD56 was present in 41% of AML cases analyzed whereas CD16 was detected
      in only 23%. All but one of the CD16+ cases coexpressed the CD56 antigen. The
      expression of these antigens was not associated with the degree of cell
      differentiation assessed either by morphological or immunophenotypical criteria,
      with the exception of the correlation observed between monocytic leukaemias and
      the expression of the CD4, CD56, and CD16 antigens. Regarding the prognostic
      value of the markers investigated, CD56 expression was associated with a tendency
      for a better outcome whereas CD7 was the only antigen that had an adverse
      influence on the survival of AML patients.

PMID- 7504773
TI  - Induction of nitric oxide synthase in asthma.
AB  - Nitric oxide (NO) is a mediator of vasodilatation and bronchodilatation
      synthesised from L-arginine by the enzyme NO synthase, which is either
      constitutive or induced by lipopolysaccharides and/or cytokines. The presence and
      function of NO synthase in normal or diseased lung is not yet clear. Asthma is
      characterised by bronchial hyperresponsiveness, epithelial damage, inflammation,
      and increased cytokine production. To investigate the presence of NO synthase in
      asthma, we immunostained bronchial biopsies from non-steroid-treated people with
      asthma and non-asthmatic controls with specific polyvalent antisera to purified
      inducible NO synthase and to a selected peptide sequence of the same enzyme.
      Immunoreactivity was seen in the epithelium and some inflammatory cells in 22 of
      23 biopsies from people with asthma, but in only 2 of 20 controls. To assess the
      relation of cytokines to NO synthase induction, bronchial epithelial cells in
      culture were stimulated with tumour necrosis factor (TNF alpha). Inducible enzyme
      immunoreactivity was found only in the treated cells. The existence of inducible
      NO synthase in human lungs suggests that increased production of NO, probably
      induced by cytokines, may be relevant to the pathology of asthma.

PMID- 7504774
TI  - Synergy between tetrandrine and FK506 in prevention of diabetes in BB rats.
AB  - Delayed administration of tetrandrine, a novel broad-spectrum anti-inflammatory
      agent, to BB rats at a dosage schedule of 20 mg kg-1 day-1 from 79 days of age
      reduced the cumulative incidence of diabetes from 73.1 to 41.7% (p < 0.01). Brief
      treatment with the potent immunosuppressive agent FK506 at a dosage schedule of
      0.5 mg kg-1 day-1 from 79 days of age for 5 days had no significant effect on the
      cumulative incidence of diabetes (66.7%, p > 0.1). However, the combination of
      tetrandrine and FK506 in the afore-mentioned dosage schedules reduced the
      incidence of diabetes to only 3.6% (p < 0.001). These results suggest that the
      strong synergy between tetrandrine and FK506 may offer a safe and effective
      therapeutic strategy for the treatment of patients with recent onset or imminent
      IDDM.

PMID- 7504775
TI  - Photochemical generation of nitric oxide from nitro-containing compounds:
      possible relation to vascular photorelaxation phenomena.
AB  - We examined the production of nitric oxide (NO) from various nitro-containing
      compounds (500 microM and 100 microM solutions in Krebs buffer, pH 7.4). Sealed
      vials containing solutions of NaNO2, N-nitro-L-arginine, 4-nitrophenol, BAY K
      8644, or N-nitro-L-arginine methyl ester were stored in the dark, under normal
      room light, or were exposed to ultraviolet light (365 nm), for 30 min (24 degrees
      C). NO was measured in the vial headspace after 30 min, using a sensitive assay
      previously established in our laboratory. Production of NO was found to be
      dependent on the intensity of light exposure for all compounds, and the highest
      degree of light-induced production of NO was found for NaNO2 and BAY K 8644
      solutions. Since NO is a relaxant of smooth muscle, these results help explain
      the increased sensitivity to relaxation by UV light of vascular and other types
      of smooth muscle in the presence of NaNO2, BAY K 8644 and N-nitro-L-arginine, as
      observed by other investigators.

PMID- 7504776
TI  - Anti-HIV effect of gramicidin in vitro: potential for spermicide use.
AB  - Gramicidin, cation channel forming ionophore with antibacterial properties, was
      studied in vitro for inhibition of human immunodeficiency virus (HIV) infection
      of MT-4 lymphocytes. Effective antiviral concentrations required for complete HIV
      inactivation were three orders of magnitude lower than 10 micrograms/ml cytotoxic
      dose. Gramicidin, routinely used as a contraceptive agent, should be considered
      for clinical application as a spermicide with antiviral activity.

PMID- 7504777
TI  - Regulation of substance P receptor system in rat striatum by chronic naltrexone
      treatment.
AB  - Chronic blockade of opioid receptors by naltrexone increases opioid peptides in
      the striatum, and up-regulates brain opioid receptors resulting in functional
      supersensitivity. Striatal SP content was increased 3.5-fold after 8 days of
      naltrexone treatment relative to control animals. The present study was
      undertaken to determine whether SP receptors in the striatum and SP receptor
      coupled second messenger system are modulated by increased striatal SP content
      induced by chronic opioid receptor blockade. The binding affinity and capacity of
      SP receptors, determined using [125I]Bolton-Hunter SP ([125I]BHSP) labeled at
      Lys3, in striatal synaptosomal membranes were not significantly altered by
      chronic blockade of opioid receptors. Although the concentrations of [Sar9,Met
      (O2)11]SP, a NK-1 receptor-specific agonist, and SP(1-7), an aminoterminal major
      metabolite of SP, required to inhibit half of [125I]BHSP binding (IC50) in
      striatal synaptosomal membranes were significantly decreased, the IC50s for SP
      and an NK-2 receptor-specific agonist, [Nle10]NK A (4-10), remained unchanged by
      chronic naltrexone treatment. The data suggest that naltrexone which has no SP
      receptor antagonistic action, not only indirectly acts on SP-ergic neurons but
      also causes a change in the apparent affinity of NK-1 receptor (as reflected by
      changes in IC50 values) in the striatum. Cellular inositol-1,4,5-trisphosphate
      [Ins(1,4,5)P3], quantified by a highly sensitive and selective radioreceptor mass
      assay, was increased in the striatum by 28% relative to control levels. With
      [3H]Ins(1,4,5)P3 as a ligand, Scatchard analyses of the concentration-dependent
      saturation curves showed that the density of striatal intracellular Ins(1,4,5)P3
      receptors was increased by 53%. The levels of SP and cellular Ins(1,4,5)P3, and
      the density of Ins(1,4,5)P3 receptors in the cerebellum, used as a positive
      control, were unchanged by chronic naltrexone treatment. The findings of opiate
      antagonist-induced increases in SP striatal content and Ins(1,4,5)P3 receptor
      densities, appear to support the concept of a role of endogenous opioids in the
      regulation of SP receptor activity. The data also suggest that inter-regulatory
      mechanisms exist between phospholipase C/phosphoinositide-coupled receptors such
      as SP receptors, and adenylate cyclase-coupled inhibitory receptors, such as
      opioid receptors.

PMID- 7504778
TI  - Immunoblotting.

PMID- 7504779
TI  - Immunogold electron microscopy: mapping tubulin isotypes on neurite microtubules.

PMID- 7504780
TI  - Postembedding immunocytochemical techniques for light and electron microscopy.

PMID- 7504781
TI  - Antiidiotypic antibodies: methods, applications, and critique.

PMID- 7504782
TI  - Molecular pharmacology. The binding issue.

PMID- 7504783
TI  - GABAA receptor needs two homologous domains of the beta-subunit for activation by
      GABA but not by pentobarbital.
AB  - The predominant inhibitory neurotransmitter of the brain, GABA (gamma
      aminobutyric acid), activates chloride-selective ion pores integral to the
      receptor complex. Subunits comprising the presumed hetero-pentameric GABA channel
      have been cloned, but little information is available on the domains important
      for activation. Rat wild-type or mutated alpha 1-, beta 2- and gamma 2-subunits
      (designated alpha, beta and gamma) were coexpressed in Xenopus oocytes and
      examined electrophysiologically. We report here the identification of two
      separate and homologous domains of the beta-subunit, each of which contributes a
      tyrosine and threonine essential for activation by GABA. Conservative
      substitution of each of these four amino acids dramatically decreased GABA
      channel sensitivity to activation by GABA and the GABA agonist muscimol. These
      substitutions, however, did not impair activation by the barbiturate
      pentobarbital, indicating these two different classes of agonists activate GABA
      channels through distinct mechanisms. We also present evidence suggesting that
      the two identified domains of the beta-subunit contribute a major component of
      the GABA receptor.

PMID- 7504784
TI  - Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and
      Stat proteins.
AB  - Binding of interferons IFN-alpha and IFN-gamma to their cell surface receptors
      promptly induces tyrosine phosphorylation of latent cytoplasmic transcriptional
      activators (or Stat proteins, for signal transducers and activators of
      transcription). Interferon-alpha activates both Stat91 (M(r) 91,000; ref. 1) and
      Stat113 (M(r) 113,000; ref. 2) whereas IFN-gamma activates only Stat91 (refs 3,
      4). The activated proteins then move into the nucleus and directly activate genes
      induced by IFN-alpha and IFN-gamma. Somatic cell genetics experiments have
      demonstrated a requirement for tyrosine kinase-2 (Tyk2) in the IFN-alpha response
      pathway and for Jak2 (ref. 6), a kinase with similar sequence, in the IFN-gamma
      response pathway. Here we investigate the tyrosine phosphorylation events on Stat
      and Jak proteins after treatment of cells with IFNs alpha and gamma and with
      epidermal growth factor (EGF). Stat91 is phosphorylated on Tyr701 after cells are
      treated with IFN-alpha and EGF, as it was after treatment with IFN-gamma (ref.
      8). We find that Jak1 also becomes phosphorylated on tyrosine after cells are
      treated with these same three ligands, although each ligand is shown to activate
      at least one other different kinase. Jak1 may therefore be the enzyme that
      phosphorylates Tyr 701 in Stat91.

PMID- 7504785
TI  - Interferon-induced nuclear signalling by Jak protein tyrosine kinases.
AB  - Interferons IFN-alpha/beta and IFN-gamma act through independent cell-surface
      receptors, inducing gene expression through tyrosine phosphorylation of
      cytoplasmic transcription factors . IFN-alpha stimulates phosphorylation and
      nuclear localization of the 84/91K and 113K subunits of latent ISGF3 (interferon
      stimulated gene factor 3), which combine with the 48K DNA-binding subunit to bind
      regulatory elements of IFN-alpha-responsive genes. IFN-gamma activates p91 alone,
      inducing IFN-gamma-responsive genes through a distinct DNA element. Genetic
      complementation studies implicated the tyrosine kinase Tyk2 in IFN-alpha
      signalling and, more recently, the related Jak2 kinase in IFN-gamma signalling.
      We now present biochemical evidence for Jak-family kinase involvement in IFN
      signal transduction. Jak1 was activated in response to IFN-alpha and IFN-gamma;
      Jak2 responded exclusively to IFN-gamma. Overexpression of either Jak1 or Jak2
      stimulated p91 DNA-binding activity and p91-dependent transcription.
      Overexpression also activated endogenous Jak kinases, suggesting that
      interactions between Jak kinases are required during interferon signalling.

PMID- 7504786
TI  - [Palliative treatment of intestinal obstruction in patients with cancer].

PMID- 7504787
TI  - [Palliative treatment of intestinal obstruction in patients with cancer].

PMID- 7504788
TI  - The stimulatory effect of chronic lithium treatment on basal thyrotropin
      secretion in rats: in vivo antagonism by methylparaben.
AB  - Chronic treatment of rats with lithium chloride was examined in order to
      determine its effects on hypothalamic monoamine and metabolite content, basal
      thyrotropin (TSH) secretion and thyroid function. The hypothalamic concentrations
      of noradrenaline (NA), dopamine (DA) and its metabolites, dihydroxyphenylacetic
      acid. (DOPAC) and homovanillic acid (HVA) in the lithium treated rats remained
      unaltered when compared to control levels. NA turnover and the NA metabolite, 3
      methoxy-4-hydroxyphenylglycol (total MHPG), were significantly lower (p < 0.01),
      whereas both serotonin (5-HT) and its metabolite, 5-hydroxyindole-3-acetic acid
      (5-HIAA), were significantly higher (p < 0.01 and p < 0.02, respectively) in the
      lithium treated rat hypothalami than in controls. Chronic lithium treatment
      significantly elevated basal TSH levels (p < 0.05). This effect was antagonized
      by methyl p-hydroxybenzoate (methylparaben, p < 0.01), which did not itself
      affect basal TSH levels. Free serum T3 and T4 levels were not significantly
      affected by chronic lithium treatment, although T4 tended to be slightly lower
      than control levels. The monoamine changes observed in the hypothalamus of
      lithium treated rats did not appear to account for the elevated TSH levels
      observed in these rats since NA activity which is generally regarded as
      stimulatory was decreased and 5-HT which has an inhibitory effect on TSH
      secretion, was increased. The elevated TSH levels may have been due to a reduced
      negative feedback inhibition of TSH release by the mildly reduced circulating T4
      levels caused by chronic lithium treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504789
TI  - Chronic administration of a nitric oxide synthase inhibitor, N omega-nitro-L
      arginine, and drug-induced increase in cerebellar cyclic GMP in vivo.
AB  - N omega-nitro-L-arginine (NG-nitro-L-arginine) is a potent nitric oxide synthase
      inhibitor which crosses the blood brain barrier and does not undergo extensive
      metabolism in vivo. In this study, effect of chronic pretreatment of N omega
      nitro-L-arginine (75 mg/kg, i.p., twice daily for 7 days) on the harmaline- (100
      mg/kg, s.c.), picrotoxin- (4 mg/kg, s.c.), pentylenetetrazole- (50 mg/kg, i.p.),
      and L-glutamic acid- (400 micrograms/10 microliters/mouse, i.c.v.) induced
      increase in cerebellar cGMP was assessed. All the four drugs produced significant
      increase in cerebellar cGMP in vehicle pretreated control animals. Cerebellar
      cGMP increased induced by harmaline, picrotoxin, and L-glutamic acid was
      attenuated in N omega-nitro-L-arginine pretreated animals. These results indicate
      that in vivo cerebellar cGMP levels are increased by the prototype excitatory
      amino acid receptor agonist, L-glutamic acid and also by the drugs which augment
      the excitatory amino acid transmission. Furthermore, parenteral chronic
      administration of N omega-nitro-L-arginine blocks NO synthase in the brain and
      hence cerebellar cGMP response in chronic N omega-nitro-L-arginine treated
      animals could be used as a tool to assess the physiological functions of nitric
      oxide in vivo.

PMID- 7504791
TI  - Neurochemical evidence that the inhibitory effect of galanin on
      tuberoinfundibular dopamine neurons is activity dependent.
AB  - The purpose of the present study was to examine the effects of galanin on the
      basal and stimulated activity of tuberoinfundibular dopaminergic (TIDA) neurons
      in male and female rats. TIDA neuronal activity was estimated by measuring
      dopamine (DA) synthesis [accumulation of 3,4-dihydroxyphenylalanine(DOPA) after
      administration of a decarboxylase inhibitor] and metabolism [ratio of 3,4
      dihydroxyphenylacetic acid (DOPAC) to DA concentrations] in terminals of these
      neurons in the median eminence. Central administration of galanin (2
      micrograms/rat, i.c.v.) produced a rapid (by 15 min) increase in plasma prolactin
      concentrations, but had no effect on the ratio of DOPAC to DA in the median
      eminence of either male or female rats. In contrast, galanin decreased the ratio
      of DOPAC to DA in the median eminence of both male and female rats whose TIDA
      neuronal activity was stimulated following administration of the DA antagonist
      haloperidol (1 mg/kg, s.c., 12 h). The galanin receptor antagonist galanin-(1-13)
      bradykinin-(2-9)-amide had no effect on the accumulation of DOPA in the median
      eminence of male rats per se, but blocked the inhibitory effects of either
      exogenous or endogenous galanin on median eminence DOPA accumulation in
      haloperidol-treated rats. These results indicate that in both male and female
      rats, galanin-induced activation of prolactin secretion is not mediated by
      changes in tonic inhibition of hormone release by TIDA neurons, and that TIDA
      neurons are responsive to the inhibitory effects of galanin only under activated
      conditions.

PMID- 7504790
TI  - Distribution of indoleamines and [3H]paroxetine binding in rat brain regions
      following acute or perinatal delta 9-tetrahydrocannabinol treatments.
AB  - The effects of delta 9-tetrahydrocannabinol (delta 9-THC) administration on the
      central serotoninergic system were evaluated by biochemical assays of tissue
      levels of indoleamines; a measure of the serotonin (5-HT) innervation was
      obtained by using [3H]paroxetine as a marker of 5-HT uptake sites. Two different
      delta 9-THC treatments were chosen, i.e.: acute and chronic perinatal maternal
      exposure. Following acute treatment (5 mg/kg), the 5-HT content increased in
      dorsal hippocampus (+35%), Substantia nigra (+61%) and neostriatum (+62%) but
      remained unchanged in cingulate cortex, Raphe nuclei, Locus coeruleus and
      anterior hypothalamus. Endogenous 5-hydroxyindole-3-acetic acid (5-HIAA)
      decreased in anterior hypothalamus (-23%) and Raphe nuclei (-21%). Following
      maternal exposure to delta 9-THC (5 mg/kg per day; from gestational day 13 to
      postnatal day 7), levels of 5-HT were increased in the neostriatum (+22%) but
      decreased in anterior hypothalamus (-25%), Raphe nuclei (-29%) and Locus
      coeruleus (-20%) of the litters. Tissue 5-HIAA was increased in anterior
      hypothalamus (+23%) and Substantia nigra (+48%). There were no changes in 5-HT
      uptake site density, determined by [3H]paroxetine binding, except for an increase
      (+50%) in the cingulate cortex of perinatal-treated rats when compared to acutely
      treated animals. The present results show that acute and maternal exposure to
      delta 9-THC produced different effects on the central 5-HT system of the
      offspring, with a clear regional specificity, but with no changes in the
      densities of 5-HT uptake sites.

PMID- 7504792
TI  - Distribution and binding sites of substance P and calcitonin gene-related peptide
      and their capsaicin-sensitivity in the spinal cord of rats and chicken: a
      comparative study.
AB  - In a comparative study, the distribution and binding sites of substance P (SP)
      and calcitonin gene-related peptide (CGRP) in the spinal cord, and their
      susceptibility towards capsaicin pretreatment were studied in rats and chicken.
      Rats: In accordance with the SP immunohistochemistry, specific binding sites for
      125I-Bolton-Hunter-SP were highest in laminae I-III. Binding sites for 125I-0Tyr
      rat-CGRP were found to be dense around the central canal, moderate in the dorsal
      and weak in the ventral horn. Neonatal capsaicin pretreatment, that reduced SP
      and CGRP immunoreactivities, increased SP specific binding sites in laminae I-III
      and X by 20 and 100%, respectively. An increase in CGRP binding density was
      detected in laminae IV, V and in the lumbar ventral horn. Displacement studies
      revealed a significant decrease of EC50-values for SP. Chicken: SP and CGRP
      immunoreactivities and SP specific binding sites were distributed similarly as in
      rats. Binding sites for radiolabelled CGRP, however, were highest in lamina X and
      in the ventral horn. Capsaicin (800 mg/kg) injected into the eggs 9 days before
      hatching had no influence on growth rate, nociception, peptide immunoreactivities
      and binding of the respective radioligands. The data demonstrated a different
      action of capsaicin on SP and CGRP and their specific binding sites in the spinal
      cord of rats and chicken and were discussed with regard to functional differences
      between these two animal species.

PMID- 7504793
TI  - Immobilization and light-dark cycle-induced modulation of serotonin metabolism in
      rat brain and of lymphocyte subpopulations: in vivo voltammetric and FACS
      analyses.
AB  - The effect of immobilization and light-dark cycle on the serotoninergic system of
      the n. raphe dorsalis and on the distribution of blood lymphocyte subpopulations
      was studied in the rat. As was shown by in vivo voltammetry, 10 min
      immobilization enhanced serotonin metabolism with a maximum 15 min after
      immobilization. The distribution of the blood lymphocytes into subpopulations was
      also affected: pan-T and T helper lymphocytes were reduced during immobilization
      and reached minimum values after 20 min recovery. The circadian rhythms of
      serotonin metabolism and the distribution of pan-T and T helper cells exhibited a
      slight phase shift if compared with each other.

PMID- 7504794
TI  - Cholinergic neurons are distributed preferentially in areas rich in substance P
      like immunoreactivity in the caudate nucleus of the adult cat.
AB  - The distribution of cells stained immunocytochemically for the cholinergic marker
      choline acetyltransferase was compared to the pattern of substance P
      immunoreactivity in the caudate nucleus of adult cats using a double-label
      immunocytochemical protocol and three-dimensional reconstructions of adjacent
      sections single-labeled for either substance P or choline acetyltransferase.
      Substance P immunoreactivity was distributed in a highly complex mosaic within
      the caudate nucleus of the cat. In the dorsal caudate nucleus, substance P-rich
      zones consisting of either clusters of substance P-positive cell bodies or fibers
      were seen against a lighter staining background. The density of cholinergic
      neurons was found to be significantly greater within these substance P-rich
      patches in comparison to surrounding regions. The pattern of substance P
      immunoreactivity within the ventral caudate nucleus differed from that in more
      dorsal regions. Clear substance P-rich patches were not seen in this region, but
      a large substance P-rich area consisting of a dense plexus of substance P
      containing fibers was visible. Embedded within this substance P-rich area were
      fairly discrete patches of light substance P staining. As in the dorsal caudate
      nucleus, increased numbers of cholinergic neurons and processes were associated
      with substance P-rich regions in the ventral caudate nucleus. Choline
      acetyltransferase-positive perikarya also appeared to be concentrated in
      substance P-rich areas in the nucleus accumbens and olfactory tubercle. The
      results of this study suggest that a close relationship exists between the
      distribution of substance P fibers and cholinergic perikarya in the striatum of
      the cat.

PMID- 7504795
TI  - Protein kinase A-mediated phosphorylation reduces only the fast desensitizing
      glycine current in acutely dissociated ventromedial hypothalamic neurons.
AB  - Modulation of glycine receptor-ionophore complex by internally perfused cyclic
      AMP was investigated and compared to that of GABA in the acutely dissociated
      ventromedial hypothalamic neurons using whole-cell and outside-out patch-clamp
      techniques. Cyclic AMP significantly reduced both GABA- and glycine-gated
      chloride currents. The reduction in glycine-induced chloride current was specific
      in that only the fast-desensitizing one gated by high concentrations of glycine
      (30-100 microM) was affected. Cyclic AMP did not modulate the non-desensitizing
      current induced by lower concentrations (6-10 microM). Addition of N-[-2
      (methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride, a protein kinase A
      inhibitor, did not have a significant effect on its own but prevented the
      attenuation of fast desensitizing glycine current induced by cyclic AMP. Both the
      reversal potential and inactivation kinetics of glycine current were not affected
      by the activation of protein kinase A, suggesting that cyclic AMP-mediated
      attenuation is not due to an enhancement of desensitization. In outside-out patch
      studies intracellular perfusion of cyclic AMP reduced the open probability of the
      100 microM glycine-activated channels without affecting that of the 6 microM
      glycine-activated channels. In conclusion, cyclic AMP selectively modulates the
      channel open frequency of the glycine receptor when activated at higher
      concentrations through a protein kinase A-mediated phosphorylation.

PMID- 7504796
TI  - Monoclonal antibodies can uncouple the main alpha-latrotoxin effects: toxin
      induced Ca2+ influx and stimulated neurotransmitter release.
AB  - A panel of monoclonal antibodies has been produced against alpha-latrotoxin using
      black widow spider venom. Five of them were characterized relative to their
      affinity for alpha-latrotoxin and ability to modify the main toxin effects--to
      increase calcium permeability of synaptosomes, to stimulate the neurotransmitter
      release and to form the ion channels in artificial lipid membrane. The results
      reported here show that: (i) the monoclonal antibodies do not alter the alpha
      latrotoxin affinity for the membrane acceptor; (ii) two monoclonal antibodies, A6
      and A24, can simultaneously inhibit the alpha-latrotoxin induced Ca2+ uptake and
      GABA release; (iii) monoclonal antibodies A4 completely block the toxin-induced
      Ca2+ uptake, but decrease partially the rate of GABA release; (iv) monoclonal
      antibodies A15 that do not modify the alpha-latrotoxin ability to stimulate Ca2+
      uptake and GABA release are able to alter the properties of channels formed by
      the toxin in the artificial lipid bilayer. From these data we hypothesize that
      the alpha-latrotoxin molecule has separate functional sites which provide a high
      affinity binding to the membrane acceptor, the toxin-induced Ca2+ uptake and
      toxin-stimulated neurotransmitter release. A separate part of alpha-latrotoxin
      molecule is responsible for the formation of cationic channels in the artificial
      lipid bilayer.

PMID- 7504797
TI  - Sequence comparisons of HTLV-I from HAM/TSP patients and their asymptomatic
      spouses.
AB  - We amplified and sequenced portions of the human T-lymphotropic virus type I
      (HTLV-I) (U3), pol, env, and pX provirus regions (1212 bp per person) from
      peripheral blood lymphocytes (PBL) of two married couples (case 1 and case 2).
      Both husbands are patients with HTLV-I-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP), and the wives are asymptomatic HTLV-I carriers. We
      selected these regions because the LTR and env regions of murine retrovirus
      models have been involved in determining tissue tropism. In addition, the
      predominant immunogenic epitope for HTLV-I-specific cytotoxic T cells obtained
      from circulating PBL of HAM/TSP patients was localized in the HTLV-I pX region.
      Our aim was to examine variations in these HTLV-I regions between affected and
      asymptomatic spouses. In the HTLV-I regions studied, we detected no sequence
      variation between each couple. These data do not favor the hypothesis that
      neurotropic mutants of HTLV-I are involved in the pathogenesis of HAM/TSP.

PMID- 7504798
TI  - In vivo comparison of zidovudine resistance mutations in blood and CSF of HIV-1
      infected patients.
AB  - Several mutations are associated with resistance to zidovudine (3'-azido-3'
      deoxythymidine, AZT) in cultured human immunodeficiency virus type 1 (HIV-1)
      isolates. Little is known as to what extent drug resistance occurs in vivo and
      whether its development within the CNS differs from that in peripheral blood. We
      therefore performed comparative nucleotide sequence analysis of the HIV-1 reverse
      transcriptase (RT) gene in proviral DNA obtained from blood and CSF of three
      patients, all of whom had progressed to AIDS under long-term zidovudine
      treatment. Six to 11 individual proviral copies per patient and compartment were
      analyzed by polymerase chain reaction (PCR)-mediated direct sequencing. In all
      samples, mutations associated with zidovudine resistance could be identified.
      They occurred in multiple HIV-1 copies in both blood and CSF, indicating that
      molecular determinants of resistance are reflected in most individual proviruses
      in vivo. Comparable positions and frequencies of mutations in isolates derived
      from both compartments do not argue for independent development of zidovudine
      resistance in CSF.

PMID- 7504799
TI  - [The importance and limits of laboratory tests for evaluating the transplacental
      passage of fetal erythrocytes into the maternal circulation].
AB  - The KBB acid elution test is used to assess the presence and extent of
      transplacental passage of fetal cells into the maternal circulation both as a
      diagnostic aid in detecting hemorrhage before birth and in monitoring pregnancies
      at risk for hemolytic disease of the newborn. However the technique is
      ineffective when an hereditary Hb-pathy with associated increase in HbF is
      present in the mother, like the HPFH, delta-beta thalassemia and other hereditary
      abnormal hemoglobins. A mother with HPFH and another mother with delta-beta
      thalassemia with false positive result of the acid-elution test are described and
      the need for an extension of the clinical and laboratory study in families with
      hereditary HbF disorder is stressed.

PMID- 7504800
TI  - Polyamine neurotoxicity is antagonized by dizocilpine in cultured chick cortical
      neurons.
AB  - Release of endogenous polyamines may contribute to neuronal loss in ischemia and
      related conditions. Primary cortical neurons were exposed to spermine and
      spermidine and subsequently assayed for [3H]ouabain binding to quantify neuronal
      loss. Neuronal survival was significantly decreased in the presence of spermine
      at 24 h (500 microM), 48 h (250 microM and 500 microM) and 72 h (10-500 microM)
      relative to controls. Co-application of 250 microM spermine and 10 microM
      dizocilpine for 48 h completely inhibited the effect of spermine alone.
      Spermidine exposure (10-500 microM) did not alter neuronal survival at any of the
      time points. These data indicate that the polyamine spermine is toxic to neurons
      in vitro and that toxicity is prevented by the NMDA-associated channel antagonist
      dizocilpine.

PMID- 7504801
TI  - Toxic effect of a beta-amyloid peptide (beta 22-35) on the hippocampal neuron and
      its prevention.
AB  - A synthetic truncated beta-amyloid peptide, beta 22-35, was shown to have a
      cytotoxic effect on cultured neurons from the rat hippocampus in serum-free
      medium. The peptide formed aggregates and typical amyloid fibrils resembling
      those of the beta-amyloid protein (AP) in neutral buffer solution and showed
      characteristic staining with Congo red and thioflavin-S. The neurotoxicity of
      beta 22-35 was suppressed by addition of calf serum, dibutyryl cAMP or insulin to
      culture medium, but not by addition of NGF or substance P. beta 22-35 had no
      effect on the glial cells. These results suggest that the AP can induce
      neurotoxicity in the hippocampal cells in vitro and the toxicity may involve a
      disorder in the intracellular signal transduction.

PMID- 7504802
TI  - Glutamate agonist-induced hippocampal lesion and nitric oxide synthase/NADPH
      diaphorase: a light and electron microscopical study in the rat.
AB  - The 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl) tetrazolium chloride
      (BSPT)-tetrazolium salt technique for the electron microscopic demonstration of
      reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) was used
      to localize nitric oxide synthase in the normal and excitotoxically lesioned rat
      hippocampus. The reaction product BSPT-formazan was shown to stain membranes
      predominantly of the endoplasmic reticulum. Apart from singular heavily labeled
      interneurons, the majority of neurons including pyramidal and granular cells and
      a few astroglial cells, light microscopically 'unstained', showed labeled
      membrane portions, but to a by far lesser extent. In lesioned areas some
      prominantly stained neurons rich in labeled membranes and surrounded by cell
      debris seemed to be largely preserved. An increased number of
      ultrahistochemically NADPH-d-stained glial cells, in particular astrocytes, was
      seen.

PMID- 7504803
TI  - Localisation of nitric oxide synthase within non-adrenergic, non-cholinergic
      nerves in the mouse anococcygeus.
AB  - Immunocytochemical staining of whole mount preparations of the mouse anococcygeus
      muscle, using antibodies to rat brain nitric oxide synthase (NOS), revealed a
      dense network of NOS-immunoreactive nerve fibres running through the tissue.
      These fibres were resistant to the sympathetic neurotoxin 6-hydroxydopamine and
      are therefore likely to be the non-adrenergic nerves which mediate relaxation of
      this smooth muscle. Further, NOS-immunoreactive fibres were absent following
      denervation by cold-storage (4 degrees C; 72 h), which has been shown to abolish
      non-adrenergic, non-cholinergic (NANC) relaxations. The results provide strong
      support for the hypothesis that the L-arginine:NO pathway is responsible for the
      generation of the NANC transmitter in the anococcygeus.

PMID- 7504804
TI  - [Interferon (Egiferon) therapy of chronic active hepatitis].
AB  - Human leukocyta interferon (Egiferon) has been administered in 10 cases having
      HBsAg positive chronic active hepatitis. The treatment was started with 3 x 3 MU
      week for one month and either with 2 x 3 MU week or 3 x 3 MU week for 2
      subsequent months. HBsAg negativity was found in cases of 4 and histological
      improvement in cases of 3 patients. The treatment was ineffective in 3 cases.

PMID- 7504805
TI  - [Notes from the Congress of otolaryngologists and audiologists in Pretoria].

PMID- 7504806
TI  - [Trisomy 21: contribution of free beta HCG for the screening of pregnancies at
      risk].

PMID- 7504809
TI  - K+ channels in the basolateral membrane of rat cortical collecting duct.
AB  - Impalement studies in isolated perfused cortical collecting ducts (CCD) of rats
      have shown that the basolateral membrane possesses a K+ conductive pathway. In
      the present study this pathway was investigated at the single-channel level using
      the patch-clamp technique. Patch-clamp recordings were obtained from
      enzymatically isolated CCD segments and freshly isolated CCD cells with the
      conventional cell-free, cell-attached and the cell-attached nystatin method. Two
      K+ channels were found which were highly active on the cell with a conductance of
      67 +/- 5 pS (n = 18) and 148 +/- 4 pS (n = 21) with 145 mmol/l K+ in the pipette.
      In excised patches the first channel had a conductance of 28 +/- 2 pS (n = 15),
      whereas the second one had a conductance of 85 +/- 1 pS (n = 53) at 0 mV clamp
      voltage with 145 mmol/l K+ on one side and 3.6 mmol/l K+ on the other side of the
      membrane. So far it has not been possible to characterize the smaller channel
      further. Excised, and with symmetrical K+ concentrations of 145 mmol/l, the
      intermediate channel had a linear conductance of 198 +/- 19 pS (n = 5). After
      excision in the inside-out configuration the open probability (Po) of this
      channel was low (0.18 +/- 0.05, n = 13) whereas in the outside-out configuration
      this channel had a threefold higher Po (0.57 +/- 0.04, n = 12). Several
      inhibitors were tested in excised membranes. Ba2+ (1 mmol/l), tetraethylammonium
      (TEA+, 10 mmol/l) and verapamil (0.1 mmol/l) all blocked this channel
      reversibly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504808
TI  - Bursting electrical activity in pancreatic beta-cells: evidence that the channel
      underlying the burst is sensitive to Ca2+ influx through L-type Ca2+ channels.
AB  - In glucose-stimulated pancreatic beta-cells, the membrane potential alternates
      between a hyperpolarized silent phase and a depolarized phase with Ca2+ action
      potentials. The molecular and ionic mechanisms underlying these bursts of
      electrical activity remain unknown. We have observed that 10.2-12.8 mM Ca2+, 1
      microM Bay K 8644 and 2 mM tetraethylammonium (TEA) trigger bursts of electrical
      activity and oscillations of intracellular free Ca2+ concentration ([Ca2+]i) in
      the presence of 100 microM tolbutamide. The [Ca2+]i was monitored from single
      islets of Langerhans using fura-2 microfluorescence techniques. Both the high
      Ca(2+)- and Bay-K-8644-evoked [Ca2+]i oscillations overshot the [Ca2+]i recorded
      in tolbutamide. Nifedipine (10-20 microM) caused an immediate membrane
      hyperpolarization, which was followed by a slow depolarization to a level close
      to the burst active phase potential. The latter depolarization was accompanied by
      suppression of spiking activity. Exposure to high Ca2+ in the presence of
      nifedipine caused a steady depolarization of approximately 8 mV. Ionomycin (10
      microM) caused membrane hyperpolarization in the presence of 7.7 mM Ca2+, which
      was not abolished by nifedipine. Charybdotoxin (CTX, 40-80 nM), TEA (2 mM) and
      quinine (200 microM) did not suppress the high-Ca(2+)-evoked bursts. It is
      concluded that: (1) the channel underlying the burst is sensitive to [Ca2+]i
      rises mediated by Ca2+ influx through L-type Ca2+ channels, (2) both the ATP
      dependent K+ channel and the CTX- and TEA-sensitive Ca(2+)-dependent K+ channel
      are highly unlikely to provide the pacemaker current underlying the
      burst.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504807
TI  - Antenatal diagnosis of pediatric surgical anomalies. Counseling the family.
AB  - Improvements in screening and diagnostic techniques now mean that hundreds of
      congenital anomalies can be antenatally diagnosed. It is, however, impossible and
      inappropriate to submit all pregnant women to a barrage of investigations.
      Screening is necessary before specific invasive investigations are initiated.
      These include history, physical examination, MS-AFP screening, estriol and hCG
      screening, and a Level II ultrasonography scan. Once at-risk pregnancies have
      been identified, a multidisciplinary team approach is commenced and further
      studies including Level II ultrasonography, amniocentesis, chorionic villus
      sampling, or cordocentesis can be performed so that an accurate diagnosis is
      available. Counseling of the parents throughout is essential so that appropriate
      decisions regarding this and further pregnancies can be made.

PMID- 7504811
TI  - Competition between frameshifting, termination and suppression at the frameshift
      site in the Escherichia coli release factor-2 mRNA.
AB  - Competition between frameshifting, termination, and suppression at the
      frameshifting site in the release factor-2 (RF-2) mRNA was determined in vitro
      using a coupled transcription-translation system by adding a UGA suppressor tRNA.
      The expression system was programmed with a plasmid containing a trpE-prfB fusion
      gene so that each of the products of the competing events could be measured. With
      increasing concentrations of suppressor tRNA the readthrough product increased at
      the expense of both the termination and the frameshifting product indicating all
      three processes are in direct competition. The readthrough at the internal UGA
      termination codon was greater than that at the natural UGA termination codon at
      the end of the coding sequence. The results suggest that this enhanced
      suppression may reflect slower decoding of the internal stop codon by the release
      factor giving suppression a competitive advantage. The internal UGAC stop signal
      at the frameshift site has been proposed to be a relatively poor signal, but in
      addition the release factor may be less able to recognise the signal with the
      mRNA in such a constrained state. Consequently, the frameshifting event itself
      will be more competitive with termination in vivo because of this longer pause as
      the release factor is decoding the stop signal.

PMID- 7504812
TI  - Structure and drug interactions of parallel-stranded DNA studied by infrared
      spectroscopy and fluorescence.
AB  - The infrared spectra of three different 25-mer parallel-stranded DNAs (ps-DNA)
      have been studied. We have used ps-DNAs containing either exclusively dA x dT
      base pairs or substitution with four dG x dC base pairs and have them compared
      with their antiparallel-stranded (aps) reference duplexes in a conventional B-DNA
      conformation. Significant differences have been found in the region of the
      thymine C = O stretching vibrations. The parallel-stranded duplexes showed
      characteristic marker bands for the C2 = O2 and C4 = O4 carbonyl stretching
      vibrations of thymine at 1685 cm-1 and 1668 cm-1, respectively, as compared to
      values of 1696 cm-1 and 1663 cm-1 for the antiparallel-stranded reference
      duplexes. The results confirm previous studies indicating that the secondary
      structure in parallel-stranded DNA is established by reversed Watson--Crick base
      pairing of dA x dT with hydrogen bonds between N6H...O2 and N1...HN3. The duplex
      structure of the ps-DNA is much more sensitive to dehydration than that of the
      aps-DNA. Interaction with three drugs known to bind in the minor groove of aps
      DNA--netropsin, distamycin A and Hoechst 33258--induces shifts of the C = O
      stretching vibrations of ps-DNA even at low ratio of drug per DNA base pair.
      These results suggest a conformational change of the ps-DNA to optimize the DNA
      drug interaction. As demonstrated by excimer fluorescence of strands labeled with
      pyrene at the 5'-end, the drugs induce dissociation of the ps-DNA duplex with
      subsequent formation of imperfectly matched aps-DNA to allow the more favorable
      drug binding to aps-DNA. Similarly, attempts to form a triple helix of the type
      d(T)n.d(A)n.d(T)n with ps-DNA failed and resulted in the dissociation of the ps
      DNA duplex and reformation of a triple helix based upon an aps-DNA duplex core
      d(T)10.d(A)10.

PMID- 7504813
TI  - Fidelity of DNA synthesis catalyzed by human DNA polymerase alpha and HIV-1
      reverse transcriptase: effect of reaction pH.
AB  - The accuracy of DNA synthesis catalyzed by the Thermus aquaticus DNA polymerase
      and the 3'-->5' exonuclease-deficient Klenow fragment of Escherichia coli DNA
      polymerase I varies as a function of reaction pH (Eckert, K.A. and Kunkel, T.A.
      (1990) Nucleic Acids Res. 18, 3739-3744; Eckert, K.A. and Kunkel, T.A. (1993) J.
      Biol. Chem. 268, 13462-13471). In the current study, we demonstrate that the
      fidelity of human DNA polymerase alpha increases 10-fold when the pH of the in
      vitro synthesis reaction is lowered from pH 8.6 to pH 6.1 (37 degrees C), as
      determined using a base substitution reversion assay to score polymerase errors
      within the lacZ alpha gene of bacteriophage M13mp2. Similarly, the base
      substitution fidelity of DNA-dependent DNA synthesis by the human
      immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) was improved nine
      fold at pH 6.5 relative to pH 8.0 (37 degrees C). A detailed comparison of HIV-1
      RT error specificity at neutral and low pH in a lacZ alpha forward mutation assay
      revealed that low pH suppresses both mispairing-mediated and misalignment
      mediated mutations; however, the characteristic HIV-1 RT pattern of mutational
      hotspots at homopolymeric sequences is retained at the lower pH. Consistent with
      the presumption that these mutations result, in part, from increased termination
      of DNA synthesis within the hotspot sequences relative to other homopolymeric
      sequences, the HIV-1 RT termination pattern during processive DNA synthesis is
      not altered by low pH. The HIV-1 RT results are in agreement with our previous
      hypothesis that the observed increase in polymerase fidelity at low pH results
      from a decreased efficiency of continuing DNA synthesis from premutational DNA
      intermediates.

PMID- 7504816
TI  - Benign prostatic hypertrophy.

PMID- 7504810
TI  - Effects of various calmodulin antagonists on Na/Ca exchange current of single
      ventricular cells of guinea-pig.
AB  - The effects of various calmodulin inhibitors were examined on the Na/Ca exchange
      current in single cardiac ventricular cells of the guinea-pig using the whole
      cell patch-clamp technique. External application of W-7 and trifluoperazine
      inhibited Na/Ca exchange current in a dose-dependent manner with IC50 values of
      13 and 7 microM, respectively. W-5 inhibited the exchange current but less
      potently than W-7. More specific calmodulin inhibitors such as CGS 9343B and
      calmidazolium did not, however, decrease the current as significantly as
      expected. All these drugs inhibited the Na current more strongly than the Na/Ca
      exchange current. Ruthenium red (RR), another type of calmodulin inhibitor, did
      not decrease the exchange current by internal application. Neither mastoparan or
      melittin (calmodulin-binding peptides) inhibited the exchange current
      appreciably. RR and the peptides did not affect the Na current either. These
      results indicate that calmodulin may not involved in the activation of cardiac
      Na/Ca exchange or the Na current. Internal application of chymotrypsin inhibited
      the blocking effect of W-7 on the Na/Ca exchange current but not that on the Na
      current. These results indicate that W-7 blocks the Na/Ca exchange current not by
      binding to calmodulin but possibly by directly affecting an internal site of the
      exchanger itself and that the inhibitory action of W-7 is different on the Na/Ca
      exchange current and the Na current.

PMID- 7504815
TI  - Confusion in the assignments of Sulfolobus sequences to Sulfolobus species.

PMID- 7504814
TI  - Group I introns interrupt the chloroplast psaB and psbC and the mitochondrial
      rrnL gene in Chlamydomonas.
AB  - The polymerase chain reaction was used to identify novel IAI subgroup introns in
      cpDNA-enriched preparations from the interfertile green algae Chlamydomonas
      eugametos and Chlamydomonas moewusii. These experiments along with sequence
      analysis disclosed the presence, in both green algae, of a single IA1 intron in
      the psaB gene and of two group I introns (IA2 and IA1) in the psbC gene. In
      addition, two group I introns (IA1 and IB4) were found in the peptidyltransferase
      region of the mitochondrial large subunit rRNA gene at the same positions as
      previously reported Chlamydomonas chloroplast introns. The 188 bp segment
      preceding the first mitochondrial intron revealed extensive sequence similarity
      to the distantly spaced rRNA-coding modules L7 and L8 in the Chlamydomonas
      reinhardtii mitochondrial DNA, indicating that these two modules have undergone
      rearrangements in Chlamydomonas. The IA1 introns in psaB and psbC were found to
      be related in sequence to the first intron in the C. moewusii chloroplast psbA
      gene. The similarity between the former introns extends to the immediate 5'
      flanking exon sequence, suggesting that group I intron transposition occurred
      from one of the two genes to the other through reverse splicing.

PMID- 7504817
TI  - Effects of bile and pancreatic digestive enzymes on permeability of the
      pancreatic duct system in rabbits.
AB  - In order to reproduce what may occur during the initial phase of biliary acute
      pancreatitis, the rabbit pancreatic duct was perfused with preincubated mixtures
      of bile and different digestive enzymes at low physiologic pressure. Permeability
      of the pancreatic duct system, serum amylase, and histological appearance of
      pancreatic tissue were studied after orthograde duct perfusion in the
      anesthetized animal. The ductal permeability was estimated by recovery of
      fluoresceinated dextran (molecular weight 17,200) in central venous blood
      following duct perfusion with this substance. Perfusion with preincubated bile
      failed to increase permeability significantly (11.10 +/- 3.04 nmol/L compared to
      5.80 +/- 2.71 nmol/L in the control group), whereas mixtures of bile and trypsin
      (27.19 +/- 5.21 nmol/L), bile and lipase (16.68 +/- 3.75 nmol/L), and bile and
      pancreatic juice (13.92 +/- 0.48 nmol/L) caused significant increases (p < 0.05).
      Similar observations were made regarding serum amylase and histology. Thus, the
      presence of mixtures of bile with pancreatic enzymes (following their prolonged
      common incubation) in the absence of elevated pressure, results in an increase in
      duct permeability for molecules up to the size range of pancreatic enzymes and
      thereby may contribute to the initiation of acute pancreatitis.

PMID- 7504818
TI  - Acute pancreatitis induced by cyclosporin A under stimulation of pancreas by
      caerulein.
AB  - Our purpose was to investigate enzymatically and morphologically the acute effect
      of the immunosuppressive agent cyclosporin A (CsA) on the exocrine pancreas of
      rats. The intravenous injection of CsA 10 and 20 mg/kg body weight (BW) increased
      the content of pancreatic amylase and protein and decreased the content of
      pancreatic DNA. Histologically, we observed intraacinar vacuolization and
      individual cell necrosis. Under stimulation of the pancreas by two
      intraperitoneal injections of caerulein 5 micrograms/kg BW at 1-h intervals
      (which did not induce any evident change in the pancreas), CsA induced a
      significant increase in serum amylase and in pancreatic wet weight in a dose
      dependent manner. CsA at doses of 10 and 20 mg/kg BW produced a significant
      increase in the content of pancreatic amylase and protein. Macroscopically, we
      observed marked pancreatic edema, venous dilatation, and patchy hemorrhage.
      Histologically, there were significant differences in the severity of intra
      acinar vacuolization, interstitial edema, neutrophil infiltration, individual
      cell necrosis, and hemorrhage, severity of which was dose dependent. Pancreatic
      ductal erosion was particularly marked following treatment with CsA 20 mg/kg BW.
      These findings indicate that CsA accelerates abnormal pancreatic enzyme secretion
      and suggest that the therapeutically recommended doses of CsA can induce acute
      pancreatitis under stimulation of the pancreas.

PMID- 7504820
TI  - Effects of parathyroid hormone on pancreatic exocrine secretion.
AB  - The role of parathyroid hormone (PTH) and calcium on pancreatic exocrine
      secretion were observed using sham-operated and parathyroidectomized dogs. First,
      exocrine secretion of the pancreas stimulated with secretin and cholecystokinin
      octapeptide (CCK-8) was examined in vivo 3 weeks after parathyroidectomy.
      Secondly, perfusion experiments of isolated pancreas in the sham-operated and
      parathyroidectomized dogs were examined. In one experiment, volume of pancreatic
      juice and bicarbonate output, but not amylase output, was decreased in the
      parathyroidectomized dogs compared with those in the sham-operated dogs; no
      participation of calcium in exocrine secretion was revealed. In another
      experiment, high doses of PTH evoked increases of pancreatic juice and
      bicarbonate output without changing amylase output; as before, no participation
      of calcium in the exocrine secretion was observed. We conclude that (a) PTH
      increases volume of pancreatic juice and bicarbonate output, and (b) pancreatic
      exocrine secretion is modified by direct effect of PTH, and the pancreatic
      ductular cells, not the acinar cells, are the target for PTH.

PMID- 7504819
TI  - Differential effects of experimentally induced chronic pancreatitis on
      neuropeptide immunoreactivities in the feline pancreas.
AB  - The distribution and concentration of calcitonin gene-related peptide (CGRP),
      substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY),
      and gastrin-releasing peptide (GRP) immunoreactivities in the pancreas of cats
      with experimentally induced chronic pancreatitis and of age- and sex-matched
      controls were investigated. By narrowing the main pancreatic duct between the
      head and the body to approximately 25% of its normal diameter, we induced within
      5 weeks chronic pancreatitis restricted to the body and tail. In control animals,
      peptide immunoreactive nerves were distributed to the islets, acini, and ducts;
      the latter were predominantly innervated by fibers immunoreactive for NPY, VIP,
      or CGRP. The vasculature received an abundant supply of NPY-, CGRP-, and, to a
      lesser extent, SP-containing axons. Within intrapancreatic ganglia, peptide
      immunoreactivities were identified in fibers and ganglion cells, with the
      exception of CGRP and SP immunostaining, which could be visualized only in
      fibers. In animals with chronic pancreatitis, the innervation pattern of each
      peptidergic system was comparable to that described in controls. However, there
      was a remarkable increase in the density and staining intensity of VIP and NPY
      immunoreactive fibers in the exocrine parenchyma and fibrous septa of the body
      and tail, where chronic pancreatitis developed. Fibers immunoreactive for CGRP
      and SP also were moderately denser than in controls, whereas those containing GRP
      immunoreactivity did not show any detectable changes. In addition, a marked
      increase of the immunostaining for VIP and, to a much lesser extent, for NPY and
      GRP, was observed in neurites supplying the head of the pancreas, which appeared
      devoid of histologically detectable pathological alterations. Radioimmunoassay
      analysis confirmed the immunohistochemical observations. The increased density of
      distinct peptidergic nerves in the pancreas with induced chronic pancreatitis
      might be the result of compensatory phenomena in response to the inflammatory
      process.

PMID- 7504821
TI  - Comparative neurochemical and neurobehavioral effects of repeated chlorpyrifos
      exposures in young and adult rats.
AB  - Neonatal (7 days old) rats are markedly more sensitive than adults (3 months old)
      to the acute toxic effects of the insecticide, chlorpyrifos (CPF). In the present
      study, we have compared the effects of subacute CPF exposures in these same age
      groups. Repeated doses of CPF (40 mg/kg, SC, every 4 days, total of 4 doses)
      caused extensive inhibition of cortical, hippocampal, and striatal cholinesterase
      (ChE) activity in adult rats at 4 (90-92%) and 14 (71-78%) days after the last
      treatment. Rats treated similarly during postnatal maturation (beginning on day
      7) showed a much lower degree of ChE inhibition (21-60%) at these time points.
      Muscarinic ([3H]quinuclidinyl benzilate, QNB) receptor binding in cortex,
      hippocampus, and striatum was reduced in adult brain at 4 (30-43%) and 14 (22
      32%) days after the final treatment, whereas receptor densities were only
      marginally affected (5-11% reduction) in young rats. Basal motor activity levels
      were not affected in either young or adult rats as a function of CPF exposure.
      CPF-treated adult rats exhibited higher activity levels after challenge with
      scopolamine (1 mg/kg, IP) at 2, 4, 6, and 8 weeks after treatment, whereas CPF
      exposure did not affect the motoric response to scopolamine in rats treated
      during postnatal maturation. These data suggest that although neonatal rats are
      more sensitive to acute lethal effects from high doses of CPF, adult rats exhibit
      more persistent neurochemical and neurobehavioral alterations following repeated,
      lower-level exposures.

PMID- 7504822
TI  - Ion transport in rat tongue epithelium in vitro: a developmental study.
AB  - The responsiveness of the rat gustatory system to monochloride salts changes
      during development. Neurophysiological recordings in the chorda tympani indicate
      that a) the taste responses to NaCl and KCl in early postnatal rats are small
      relative to NH4Cl, b) both salts become more potent stimuli as the animal
      matures, and c) the developmental increase is accompanied by an increase in
      sensitivity of the NaCl response to the sodium transport blocker amiloride. We
      measured ion transport properties of in vitro tongue epithelia from Wistar rats.
      When the tissue is mounted in an Ussing chamber, the short-circuit current
      responses to NaCl and KCl are small in the neonatal rat and increase during
      development in postweaning and adult animals. Amiloride sensitivity of the NaCl
      response also increases with age. This study confirms that increased sensitivity
      of the rat gustatory system to NaCl with age reflects changes in the peripheral
      membranes. The results support hypothesis that the increased sensitivity is due
      to amiloride-sensitive membrane components being added or becoming functional.

PMID- 7504823
TI  - Mapping the dynamics of a bursting neuron.
AB  - The anterior burster (AB) neuron of the lobster stomatogastric ganglion displays
      varied rhythmic behavior when treated with neuromodulators and channel-blocking
      toxins. We introduce a channel-based model for this neuron and show how
      bifurcation analysis can be used to investigate the response of this model to
      changes of its parameters. Two dimensional maps of the parameter space of the
      model were constructed using computational tools based on the theory of nonlinear
      dynamical systems. Changes in the intrinsic firing and oscillatory properties of
      the model AB neuron were correlated with the boundaries of Hopf and saddle-node
      bifurcations on these maps. Complex rhythmic patterns were observed, with a
      bounded region of the parameter plane producing bursting behavior of the model
      neuron. Experiments were performed by treating an isolated AB cell with 4
      aminopyridine which selectively reduces gA, the conductance of the transient
      potassium channel. The model accurately predicts the qualitative changes in the
      neuronal voltage oscillations that are observed over a range of reduction of gA
      in the neuron. These results demonstrate the efficacy of dynamical systems theory
      as a means of determining the varied oscillatory behaviors inherent in a channel
      based neural model. Further, the maps of bifurcations provide a useful tool for
      determining how these behaviors depend upon model parameters and comparing the
      model to a real neuron.

PMID- 7504824
TI  - The effect of the MAO-A selective inhibitor brofaromine on the plasma and urine
      concentrations of some biogenic amines and their acidic metabolites in bulimia
      nervosa.
AB  - 1. Brofaromine or placebo were administered to female bulimia nervosa patients
      over a period of eight weeks. Plasma and urinary trace amines, their acidic
      metabolites and the acidic metabolites of the catecholamines and serotonin were
      assessed prior to treatment and at four and eight weeks after commencement of
      treatment. 2. The levels of both plasma and urinary homovanillic and
      vanilmandelic acids declined significantly during the first four weeks of
      treatment with brofaromine and then partially recovered to pre-drug levels by the
      eighth week. 5-Hydroxyindoleacetic acid levels were not affected by drug
      treatment at the times assessments were made. Urinary tryptamine increased
      significantly during the first four weeks of brofaromine treatment then partially
      recovered towards pre-drug levels by the eighth week. No effect from placebo
      treatment was observed.

PMID- 7504825
TI  - Immunopharmacologic modulation of experimental allergic encephalomyelitis: low
      dose cyclosporin-A treatment causes disease relapse and increased systemic T and
      B cell-mediated myelin-directed autoimmunity.
AB  - Therapies with immunosuppressive drugs in autoimmune experimental diseases often
      down-regulate disease but sometimes may lead to paradoxical disease exacerbation.
      To elucidate possible mechanisms behind such phenomena the effects were studied
      of mitoxantrone (Mx) and cyclosporin A (CsA) given at high and low doses on
      clinical course, and on autoreactive T- and B-cell responses in actively induced
      experimental allergic encephalomyelitis (EAE) in Lewis rats. Treatment with Mx
      and high dose CsA abrogated EAE and decreased dramatically the measured immune
      responses compared to vehicle-treated control EAE rats. Low-dose CsA treatment
      caused a disease relapse 20-30 days post immunization (p.i.). This relapse was
      accompanied by increased numbers of cells spontaneously producing IFN-gamma in
      the CNS and regional lymph nodes. Furthermore, anti-myelin and anti-MBP secreting
      cells were increased as were numbers of primed T cells that produced IFN-gamma in
      response to myelin antigens. It was concluded that these aspects of the myelin
      autoreactive immune response correlated well with clinical disease and are useful
      in evaluating immunotherapeutic intervention. Low-dose CsA treatment may
      interfere with systemic down-regulatory mechanisms acting on both T- and B-cell
      myelin-directed autoimmunity.

PMID- 7504826
TI  - Human naive and memory T-helper cells display distinct adhesion properties to
      ICAM-1, LFA-3 and B7 molecules.
AB  - In this paper the contribution of different accessory molecules to the adhesion
      of resting, naive and memory CD4+ T cells was examined utilizing a panel of CHO
      cell transfectants as model antigen-presenting cells (APCs). CD4+ T lymphocytes
      demonstrated strong adhesion to HLA-DR4 transfected CHO cells co-expressing B7,
      ICAM-1 or LFA-3 molecules, suggesting that all three adhesion pathways is
      utilized by resting CD4+ cells. Monoclonal antibodies (MoAbs) against the
      corresponding receptors on T cells, e.g. anti-CD28, anti-LFA-1 beta and anti-CD2,
      inhibited completely T-cell adhesion to natural ligands expressed on transfected
      CHO cells. Pretreatment of CD4+ T cells with NKI-L16 MoAb, which interact with an
      activation epitope on LFA-1 alpha chain, enhanced adhesion to ICAM-1 but not B7
      or LFA-3-expressing CHO cells. Analysis of T helper-cell subsets revealed that
      memory T cells bound several fold stronger to ICAM-1 expressing transfectants
      compared to the CD4+ 45RA+ naive T cells, whereas adhesion to B7, LFA-3- and
      B7/LFA-3-expressing CHO cells was similar in both T-cell subsets. The kinetics of
      adhesion of naive and memory CD4+ T cells to ICAM-1 was rapid and similar in both
      subsets. The NKI-L16 MoAb multiplied several times ICAM-1-dependent adhesion in
      naive compared to memory cells, which enabled the naive cells to reach a similar
      adhesion level as memory cells. The results suggest that resting naive CD4+ T
      cells utilize preferentially the CD2/LFA-3 or CD28/B7 adhesion pathways upon
      adhesion to APCs, while memory CD4+ T cells utilize the CD2/LFA-3, CD28/B7 and
      LFA-1/ICAM-1 adhesion pathways. The NKI-L16 MoAb-induced upregulation of adhesion
      involves an increased affinity of LFA-1 for its ligand and not a change in the
      number of LFA-1 molecules. This is compatible with a view that naive cells
      express a large number of inactive LFA-1 molecules, whereas memory cells express
      preferentially activated LFA-1 molecules. The inherent low number of active LFA-1
      molecules on naive CD4+ T cells may be important in keeping these cells in a
      resting state.

PMID- 7504827
TI  - CD5-positive and CD5-negative rheumatoid factor-secreting B cells in IgA
      nephropathy, rheumatoid arthritis and Graves' disease.
AB  - The relative contributions of CD5+ and CD5- B-cells in production of rheumatoid
      factors (RF) was evaluated in polyclonally activated B-cells from patients with
      IgA nephropathy (IgAN), rheumatoid arthritis (RA) and Graves' disease (GD). In
      IgAN and RA, diseases in which RFs are believed to be involved in pathogenesis,
      there were 10- and 4-fold decreases respectively in CD5+ IgG-RF-secreting B-cells
      compared with controls. Furthermore, the number of CD5- IgG-RF- and IgA-RF
      secreting B-cells were increased 12- and 14-fold in IgAN and 9- and 4-fold in RA.
      Such abnormalities were not apparent in GD, in which RFs have not been implicated
      in pathogenesis. These findings are compatible with the concept of CD5+ RF
      secreting B-cells normally acting to prevent production of potentially pathogenic
      RFs by CD5- B-cells. When IgAN or RA patients' B-cells were activated in the
      presence of control instead of autologous CD4+ cells, numbers of RF-secreting CD5
      B-cells were reduced to the levels seen with control B-cells plus control T
      helper cells. Presumably lymphokine secretion profiles of T-helper cells would be
      important in determining whether CD5+ or CD5- B-cells are activated to secrete
      RFs, and perhaps therapeutic manipulation of these profiles could restore normal
      activity of CD5+ B-cells in IgAN and RA.

PMID- 7504828
TI  - Peptide binding sites recognized by anti-mucin (MUC2) monoclonal antibodies.
AB  - Multiple genes coding for human mucins have been identified (MUC 1-5) and here
      monoclonal antibodies (MoAb) to a gastrointestinal mucin--MUC2 are examined. The
      antibodies were made to a synthetic peptide representing a single repeat in the
      core protein of the variable number of tandem repeat region. Using the six-mer
      overlapping peptides synthesized on polyethylene pins, different binding sites
      were detected by five anti-MUC 2 MoAbs. These contained amino acids: STTT, PTT,
      GTQTP, TPTP and PTTT (one antibody), and TPTPT. The repeat region of MUC2
      essentially is hydrophobic, but contain useful immunogenic sites. This
      information will be useful for studying the structure and function of MUC2.

PMID- 7504829
TI  - [Hypothyroidism followed by hyperthyroidism under treatment with amiodarone].
AB  - Hypothyroidism followed by hyperthyroidism is described in two patients treated
      by amiodarone. Euthyroidism was rapidly restored after treatment with antithyroid
      drugs and potassium perchlorate. The physiopathology of amiodarone-induced
      hypothyroidism is discussed. Withdrawal of amiodarone is advised in the case of
      both hypothyroidism and hyperthyroidism.

PMID- 7504830
TI  - [Developmental tasks in aging].

PMID- 7504831
TI  - [Incidence of dementia in the city of Zurich and the urban health management
      concept].

PMID- 7504832
TI  - [The family and Alzheimer's disease: making choices].

PMID- 7504833
TI  - [Alzheimer's disease followed in a single case].
AB  - Descriptions of Alzheimer's disease are usually based on the observation of
      populations of patients. Their advantage is the systematic analysis of signs and
      symptoms according to a logical approach enumerating the involvement of
      neurological, neuropsychological, affective and behavioral fields. Their
      disadvantage is to neglect the natural evolutive way and the subtle gearing of
      these diverse aspects of the disease. This paper aspires to bring a complement to
      the necessary systematic knowledge, by the description of a patient who has been
      followed regularly every 3 months for 4 and a half years. It describes the
      evolution as it is lived by the patient and his spouse, and as it is observed by
      the clinician. Three main facts are inferred. The first is the precocious
      involvement of two functions particularly affected later: language and the
      ability of identifying others. The second is with the evolution of the disease
      the identification, in the neuropsychological domain, of some tests which show no
      or little alteration, of some others altered from the outset, the majority
      deteriorating progressively. The third is the observation of a brisk and
      definitive worsening following a transient ischemic attack, demonstrating the
      vulnerability of these patients when the disease has reached an advanced stage.

PMID- 7504834
TI  - [Neuropathology of Alzheimer's disease: recent experimental aspects].
AB  - This review summarizes some recent aspects of the research development in the
      field of Alzheimer's disease. In particular, the presentation of a cohesive view
      of the molecular, cellular and anatomical aspects of Alzheimer's disease is
      attempted. Thus, the distribution of the classical lesions of Alzheimer's disease
      and the degree of neuronal specialization at the morphologic, connectivity and
      molecular levels is discussed in the idea of defining a cellular profile that
      would characterize neuronal populations preferentially affected by the
      degenerative process. These data indicate that certain neurons of origin of
      specific intracortical projections and displaying a high degree of cellular
      specialization are selectively vulnerable in Alzheimer's disease and show an
      increased sensitivity even in normal brain aging. The study of such neuronal
      populations in dementia as well as in aging or in animal models may lead to the
      development of therapeutic agents that would protect these particular cells
      against the mechanisms of the degenerative process.

PMID- 7504835
TI  - [Internal representations of pregnant patients of their child and attempt of
      their prognostic assessment].

PMID- 7504836
TI  - [Psychopathology in nunneries].
AB  - The psychiatric observations of female adepts and nuns of Christian monastic
      congregations, seen as in- or outpatients of a mental hospital of an order, are
      reported, mainly focussing on schizophrenic and schizophreniform psychoses and
      severe personality disorders. The patient statistics and sketches of
      psychopathology and the dynamics of the disorders are presented. The selection
      process for adepts for the monastic profession and the need for education of the
      responsible leaders in psychological, psychotherapeutic and psychiatric issues
      are considered.

PMID- 7504837
TI  - L-dopa resistant parkinsonism in an adult woman with a cyst in the posterior
      fossa.
AB  - We report a case of a woman with L-Dopa resistant asymmetrical parkinsonism with
      a posterior fossa cyst compressing the lower brainstem on MR. She did not show
      improvement in any of her symptoms after cysto-cardiac derivation. It was not
      possible to delineate if this was a case of a new malformative syndrome or the
      coincidence of two different disorders.

PMID- 7504838
TI  - [Early diagnosis of septic complications in the postoperative period by
      determination of acute phase proteins].
AB  - The authors submit the results of the follow-up of the dynamics of 10 acute stage
      plasma proteins (up to the 7th day) in two surgical model situations: 1. planned
      operation of colorectal carcinoma by an intraabdominal approach and 2. operation
      of extensive varicosities of the lower extremities. As reference groups 3.
      healthy subjects (blood donors) were used and 4. patients with developed
      postoperative sepsis. Based on the results, the authors provide evidence of the
      asset of some selected indicators they assessed such as transferrin, prealbumin,
      alpha-1 acid glycoprotein (orosomucoid) and C reactive protein, for the early
      diagnosis of postoperative septic complications.

PMID- 7504840
TI  - Anti-idiotype vaccines for immunity to bacterial polysaccharides: induction of
      functional antibodies to polysaccharide antigens of Pseudomonas aeruginosa.

PMID- 7504839
TI  - Evolution and pathophysiology of the human natural anti-alpha-galactosyl IgG
      (anti-Gal) antibody.
AB  - Anti-Gal is a human natural antibody which interacts specifically with the
      mammalian carbohydrate structure Gal alpha 1-3Gal beta 1-4GlcNAc-R, termed, the
      alpha-galactosyl epitope. This antibody constitutes approximately 1% of
      circulating IgG in human serum and is produced, upon stimulation, by 1% of
      circulating B lymphocytes. Anti-Gal is also present as IgA antibodies in body
      secretions such as saliva, milk and colostrum. The antigenic source for the
      constant production of anti-Gal seems to be the alpha-galactosyl-like epitopes
      found on many bacteria of the gastrointestinal flora. Whereas anti-Gal is
      abundant in humans, apes and Old World monkeys, it is absent from New World
      monkeys, prosimians and nonprimate mammals. The latter group of species produces,
      however, large amounts of alpha-galactosyl epitopes (> 10(6) epitopes per cell).
      It is estimated that anti-Gal appeared in ancestral Old World primates less than
      28 million years ago, possibly as a result of an evolutionary event which exerted
      a selective pressure for the suppression of alpha-galactosyl epitopes expression
      by inactivation of the gene for the enzyme alpha 1,3 galactosyltransferase. This
      also resulted in the loss of immune tolerance to the alpha-galactosyl epitope and
      the production of anti-Gal. The physiologic role of this antibody is not clear as
      yet. It may participate in the protection against gastrointestinal bacteria. In
      addition it seems to contribute to the removal of normal and pathologically
      senescent red cells by interacting with the few hundred cryptic alpha-galactosyl
      epitopes which are exposed de novo in the course of red cell aging, thereby
      opsonizing these cells for phagocytosis by reticuloendothelial macrophages. The
      alpha-galactosyl epitope has been found to be aberrantly expressed on human cells
      and the interaction of anti-Gal with such epitopes may result in autoimmune
      disease. Preliminary data suggest such a mechanism in Graves' disease. Anti-Gal
      has been found to interact with therapeutic recombinant proteins expressing alpha
      galactosyl epitopes, but so far there is no indication that it affects the half
      life in the circulation and the biologic activity. Detection of anti-Gal in the
      seminal fluid and in the cerebrospinal fluid may serve as a simple means for
      assessment of damage to the blood-genital tract barrier or the blood-brain
      barrier. Studies on the interaction of anti-Gal with aberrantly expressed alpha
      galactosyl epitopes on human cells may elucidate the possible role of anti-Gal in
      human autoimmune diseases.

PMID- 7504841
TI  - Antibody variable region glycosylation: biochemical and clinical effects.

PMID- 7504842
TI  - Major histocompatibility complex class II association and induction of T cell
      responses by carbohydrates and glycopeptides.

PMID- 7504843
TI  - Effect of antibody to transforming growth factor beta on bleomycin induced
      accumulation of lung collagen in mice.
AB  - BACKGROUND: Increased production of transforming growth factor beta (TGF-beta)
      seems to have an important role in the pathophysiology of bleomycin induced lung
      fibrosis. This is attributed to the ability of TGF-beta to stimulate infiltration
      of inflammatory cells and promote synthesis of connective tissue, leading to
      collagen deposition. METHODS: The study was designed to evaluate the antifibrotic
      potential of TGF-beta antibody in mice treated with bleomycin, which is a model
      of lung fibrosis. Under methoxyflurane anaesthesia, each mouse received
      intratracheally either 50 microliters sterile isotonic saline or 0.125 units
      bleomycin in 50 microliters. Within five minutes after the instillation, mice
      received into the tail vein 100 microliters non-immune rabbit IgG, TGF-beta 2
      antibody, or a combination of TGF-beta 2 and TGF-beta 1 antibodies at various
      dose regimens. Mice were killed 14 days after the instillation and their lungs
      processed for morphological and biochemical studies. RESULTS: Administration of
      250 micrograms of TGF-beta 2 antibody after instillation of bleomycin followed by
      100 micrograms on day 5 and 100 micrograms on day 9 significantly reduced the
      bleomycin induced increases in the accumulation of lung collagen from 445.8
      (42.3) micrograms/lung to 336.7 (56.6) micrograms/lung at 14 days. Similarly, the
      combined treatment with 250 micrograms TGF-beta 2 antibody and 250 micrograms TGF
      beta 1 antibody after bleomycin instillation followed by 100 micrograms of each
      antibody on day 5 also caused a significant reduction in bleomycin induced
      increases in lung collagen accumulation and myeloperoxidase activity at 14 days.
      CONCLUSIONS: These results suggest that TGF-beta has an important role in the
      aetiology of bleomycin induced lung fibrosis; the neutralisation of TGF-beta by
      systemic treatment with its antibodies offers a new mode of pharmacological
      intervention which may be useful in treating lung fibrosis.

PMID- 7504844
TI  - Textbook error: the structure of alpha-keratin.

PMID- 7504845
TI  - Diagnostic immunoelectron microscopy in surgical pathology: assessment of various
      tissue fixation and processing protocols.
AB  - We have investigated various tissue fixation and embedding protocols in an effort
      to allow expanded use of immunoelectron microscopy in diagnostic surgical
      pathology. A sample of normal human small bowel mucosa was processed using seven
      different methods for subsequent postembedding localization of chromogranin A. In
      addition, several archival cases of neuroendocrine tumors previously fixed and
      routinely embedded for electron microscopy, stored in formalin, or snap-frozen
      were retrieved and variously processed for chromogranin A localization at the
      ultrastructural level. Precise localization of chromogranin A in dense core
      granules was achieved with protein A-gold on sections from all of the processing
      methods. The methods included retrieval into mild fixative of previously formalin
      fixed or snap-frozen tissues followed by embedding in Lowicryl K4M (Polysciences
      Ltd., Eppelheim, Germany). Thus, tissue processed without foresight of the need
      for immunoelectron microscopic localization can be successfully used. Since
      embedding of tissues in Lowicryl K4M has been shown to preserve a variety of
      antigens, it may prove to be a superior resin for use in diagnostic
      immunoelectron microscopy.

PMID- 7504846
TI  - [Whipple disease. A rare systemic disorder with multiple manifestations].
AB  - Mb. Whipple is a rare systemic disorder with multiple manifestations. We present
      a case-story demonstrating the typical course: migrating, non-deforming
      arthralgies are years later followed by diarrhoea, loss of weight, fatigue and
      pronounced biochemical disturbances. Intestinal biopsy shows numerous PAS
      positive, diastaseresistent macrophages, and antibiotic treatment is initiated.
      After a somewhat prolonged course, complicated with Giardiasis and endocarditis,
      the patient recovers. Four months after the cessation of antibiotic treatment,
      however, the patient shows clinical signs of relapse, and treatment is restarted.
      The etiological agent has recently been identified as a gram-positive
      actinomycete called Tropheryma Whippleii. There are some, but not unequivocal,
      signs of a cellular immunodeficiency, perhaps predestinating certain patients to
      the disease. The course is usually favourable, when treated with relevant
      antibiotics. Relapse is not uncommon, and is very problematic when the CNS is
      involved. Therefore, a combination treatment with good penetration of the blood
      brain barrier is recommended--e.g. two weeks treatment with parenterally
      administered streptomycin and benzylpenicillin followed by sulphamethoxazole
      trimethoprim orally for one year.

PMID- 7504847
TI  - [Cerebral dysfunction after prolonged use of opioids].
AB  - Cerebral dysfunction due to long-term treatment with opioids is a problem of
      increasing relevance because of the rapidly growing use of opioids. A review of
      psychomotor and cognitive test methods is given, including their application in
      patients on long-term opioid treatment. The findings of the most valid studies on
      cancer patients in long-term treatment with opioids are an increase in continuous
      reaction time and subjective sedation score regardless of the routes of
      administration. Studies of drug addicts in long-term treatment with opioids seem
      to reflect a lowering of the general level of activity. According to recent
      studies, patients with chronic non-malignant pain conditions are responsible for
      the major part of the total opioid consumption. So far, no studies of cerebral
      dysfunction have been performed on this group of patients. Further research
      should concentrate on the use of few valid psychomotor and cognitive tests and
      should include patients with chronic non-malignant pain conditions.

PMID- 7504848
TI  - Natural history of prostatism: factors associated with discordance between
      frequency and bother of urinary symptoms.
AB  - The objective of this study was to assess the association between frequency and
      bother of urinary symptoms in a population-based cohort of men and to identify
      psychosocial factors that are related to reporting heightened or subdued bother
      relative to symptom frequency. The survey was conducted among men aged forty to
      seventy-nine years in Olmsted County, Minnesota, the baseline component of a
      prospective cohort study. Men were queried about the frequency of urinary symptom
      occurrence and the perceived bother associated with the symptoms. A regression
      analysis of American Urologic Association (AUA) bother scores on AUA frequency
      scores demonstrated a tight correspondence (r2 = 0.71). Men with bother scores
      greater than predicted from their frequency scores were more likely to have
      sought health care for their urinary symptoms than men whose bother was close to
      predicted (14 versus 5 percent, respectively). These men with heightened bother
      were older, poorer, more anxious, and had lower general psychologic well-being
      scores than the men whose bother was similar to that expected from their reported
      frequency. Men whose bother was lower than would be expected were less likely to
      have sought health care for urinary symptoms in the past year (3%) but were of
      similar age and socioeconomic status as compared with men whose bother was close
      to expected. These men, however, were more depressed than men whose bother was
      commensurate with reported frequency. While the men who reported greater bother
      than expected from their symptom frequency were more likely to have sought
      medical care for urinary symptoms in the past year, it is not clear whether this
      greater health-care-seeking behavior is because bother captures an additional
      component of urologic disease or is a manifestation of psychosocial differences.

PMID- 7504849
TI  - Comparative analysis of fluctuation of serum tumor markers in advanced cancer of
      prostate.
AB  - Serial serum prostate tumor markers (acid phosphatase, prostate-specific antigen
      Yang, prostate-specific antigen-Hybritech, lipid-associated sialic acid in
      plasma, and tissue polypeptide antigen) were obtained every four hours during a
      twenty-four-hour interval from men with Stage D adenocarcinoma of the prostate.
      No therapeutic or diagnostic manipulations occurred during sample procurement, so
      that the amount of fluctuation in these serum prostate cancer markers could be
      determined. The average co-efficient of variation for acid phosphatase 28.8,
      prostate-specific antigen-Yang 8.85, prostate-specific antigen-Hybritech 7.2,
      lipid-associated sialic acid in plasma (LASA-P) 6.19, and tissue polypeptide
      antigen (TPA) 14.75 indicate that prostate-specific antigen determined by either
      method fluctuates minimally, indicating stability and, because it is prostate
      cancer specific, is the most useful tumor marker tested.

PMID- 7504850
TI  - Bladder neck preservation and its impact on positive surgical margins during
      radical prostatectomy.
AB  - To modify the bladder neck dissection during radical prostatectomy, in an effort
      to improve continence and diminish the incidence of anastomotic stricture,
      without compromising the primary surgical objective of complete cancer removal.
      Between December 1991 and August 1992, 50 patients underwent radical retropubic
      prostatectomy with anatomic dissection and preservation of the bladder neck and
      most proximal portion of the prostatic urethra, thus creating a mucosal cuff for
      anastomosis to the urethral stump. There was tumor at the inked margin in 18
      patients (36%), however, in only 3 instances (6%) was there tumor at the bladder
      neck margin. In no instance was the bladder neck margin the only positive margin.
      At a minimum follow-up of six months, all patients are fully continent during
      routine activities, and in no patient has an anastomotic stricture developed.
      Anatomic dissection and preservation of the bladder neck and proximal urethra
      does not compromise surgical margins. We believe this technique may play a role
      in preservation of continence after radical prostatectomy and probably decreases
      the likelihood of anastomotic stricture, by allowing for a circumferential mucosa
      to-mucosa anastomosis without the need for bladder neck reconstruction.

PMID- 7504851
TI  - Urolase laser prostatectomy in patients on warfarin anticoagulation: a safe
      treatment alternative for bladder outlet obstruction.
AB  - Three patients with symptomatic bladder outlet obstruction due to benign
      prostatic hyperplasia underwent laser prostatectomy using a Neodymium:YAG source
      delivered with the Urolase right-angle laser fiber. All patients had significant
      underlying medical problems, and all were fully anticoagulated with oral warfarin
      (mean prothrombin time 17 seconds). Two were in urinary retention with indwelling
      catheters preoperatively. Laser prostatectomy was performed in each case without
      change in the medical regimen, including continuous warfarin dosing. No
      complications occurred, and in particular, no early or late bleeding episodes
      were encountered. All are symptomatically improved and catheter-free on follow
      up. Laser prostatectomy provides a new and safe therapeutic option in the
      management of these high-risk patients.

PMID- 7504852
TI  - Antigen recognition on Anaplasma marginale and bovine erythrocytes: an electron
      microscopy study.
AB  - The reactivity of sera from Anaplasma marginale-infected bovine with red blood
      cells and with purified anaplasma bodies was analyzed by electron
      immunomicroscopy. Red blood cells from non-infected and from anaplasma-infected
      cows and A. marginale bodies separated from parasitized erythrocytes, were
      incubated with control, pre-immune and immune sera followed by anti-bovine IgG
      Peroxidase. Immune sera from cows infected with the venezuelan and Florida
      isolate reacted with red blood cell membranes from normal and infected bovines,
      while sera from non-infected cows did not. The immune sera also recognized
      epitopes localized on the cell wall, membrane and on unidentified intracellular
      structures of the purified anaplasma bodies. Thus, we propose that A. marginale
      infection may cause structural and biochemical modifications of the plasma
      membrane of the bovine red blood cells during its intraerythrocytic cycle. This
      in turn could elicit an autoimmune type of response against its own cells that
      would stimulate erythrophagocitosis. The strong reactivity of the immune sera
      with the Anaplasma bodies suggests that the bovine immune system also recognizes
      epitopes located on the parasite.

PMID- 7504853
TI  - Miscellaneous uses of anabolic steroids.
AB  - The original list of indications for anabolic-androgenic steroids has been
      reduced to those discussed in this publication so far and to mammary carcinoma,
      deficiency states and growth disorders. In disseminated endocrine-responsive
      mammary carcinoma in the female, anabolic drugs have a proven palliative effect
      in some 20 to 40% of patients, arresting tumour growth for up to 12 months and
      improving the patient's general condition. In high doses they can cause a
      disturbing increase in libido. Patients with deficiency states can, irrespective
      of the cause, benefit from adjunctive anabolic steroid treatment, provided their
      food supply is adequate. Positive effects are exerted by the anabolic agents'
      protein anabolic and anticatabolic actions, by psychic stimulation of the patient
      and by enhancement of recovery. Current trials strongly indicate that oral
      anabolic drugs administered alone or in combination with growth hormone or
      thyroid preparations are of therapeutic value in growth disorders such as
      constitutional delay of growth and puberty, hypopituitary dwarfism, chronic renal
      diseases and in Turner's syndrome.

PMID- 7504854
TI  - [Hemorheologic effects of hydroxyethyl starch 200/0.5, dextran 40,
      oxypolygelatine and full electrolyte solution over 48 hours].
AB  - Four patient groups (n = 28 patients) received in a randomised clinical trial a
      single intravenous infusion of 500 ml of 10% dextran 40, 3.5% oxypolygelatine, 6%
      hydroxyethyl starch 200/0.5 or saline solution, respectively. The
      haemorheological parameters haematocrit, plasma viscosity and erythrocyte
      aggregation were followed up during 48 hours. In our study oxypolygelatine showed
      better rheological results than HAES 200/0.5. Dextran 40 especially increased the
      plasma viscosity and erythrocyte aggregation, so that we cannot recommend this
      plasma substituent for hypervolemic haemodilution.

PMID- 7504855
TI  - [A rare complication of percutaneous endoscopic gastrostomy: metastasis of
      adenocarcinoma of the stomach in the area of the gastric stoma].
AB  - A percutaneous endoscopic gastrostomy (PEG) was placed by the "pull technique" in
      a 67-year old patient before initiation of palliative radiation therapy of a
      gastric adenocarcinoma invading the distal esophagus. A tumor metastasis
      developed in the peristomal area and around the gastrocutaneous fistula tract; it
      was most likely caused by implantation of tumor tissue adhering to the PEG tube.
      This complication of PEG placement appears to be very rare.

PMID- 7504856
TI  - [Pathophysiologic concepts and protective possibilities in experimental
      pancreatic lesions].
AB  - Experimental pancreatic lesions can be induced by a number of different
      procedures, e.g. pancreatic hyperstimulation, intraductal application of bile
      acids, feeding choline deficient diet, obstruction of pancreatic duct, or
      reducing pancreatic blood flow. The pathogenetic mechanisms leading to pancreatic
      lesions include basolateral enzyme secretion, acinar cell polarisation defect,
      intracellular activation of proteases, and the production of free radicals and
      other active metabolites. The importance of these individual mechanisms in the
      production and progression of different experimentally-induced pancreatic lesions
      remains speculative. These pathogenetic concepts have inspired the study of a
      number of substances likely to protect the pancreas and prevent the pancreatic
      lesions. This paper gives an overview of the pathogenetic concepts of development
      of and protection against experimental pancreatic lesions produced in animal
      models. Special mention has been made of an animal model of pancreatic lesion
      produced by immunosuppressives.

PMID- 7504857
TI  - Immunogenicity in mice of tandem repeats of an epitope from herpes simplex gD
      protein when expressed by recombinant adenovirus vectors.
AB  - The antigenic and immunogenic potential was examined of human adenovirus type 5
      (Ad) recombinants carrying and expressing from one to four tandem repeats of a
      linear neutralizing epitope from the gD protein of herpes simplex virus type 1
      (HSV-1) as a fusion with the beta-galactosidase protein. The fusion proteins
      produced by these Ad vectors in infected cell culture reacted with a herpes
      simplex virus (HSV) epitope-specific monoclonal antibody to a degree dependent on
      the number of epitope repeats in the protein. Mice immunized by intraperitoneal
      injection of the Ad vectors developed an anti-HSV immune response as measured by
      ELISA and by HSV-1 neutralization assays. The mean antibody titre induced by a
      single injection of the Ad vector increased with the number of epitope repeats
      expressed by the recombinant. Any animal that had developed a serum-neutralizing
      titre of at least 1:80 survived challenge with a normally lethal dose of HSV-2
      administered by the intraperitoneal route. Recombinant vectors expressing four
      repeats of the HSV epitope were as effective in antibody induction and protection
      as an adenovirus vector carrying and expressing the entire HSV gD protein. These
      results suggest that the expression of tandem repeats of appropriate epitopic
      sequences by adenovirus vectors may provide a safe and effective method of
      immunizing against HSV infection.

PMID- 7504858
TI  - Immune response related to the molecular structure of a peptide from the cholera
      toxin B subunit.
AB  - Three forms of a peptide P50-75 from the cholera toxin B subunit in the absence
      of carrier or adjuvant were administered orally or intraperitoneally to C57Bl/6J
      mice. Mice were given P50-75 as the free monomer, as an octamer synthesized on
      the seven polylysine core proposed by Tam (S), or as an octamer synthesized on
      the epsilon-amino groups of a chain of eight Lys-Gly-Gly units (C). P50-75,
      presented to the immune system, as monomer or polymers, generated similar serum
      titres of anti-cholera toxin (CT) antibodies. However, mice immunized orally with
      the polymers S and C were better protected against the intestinal effects of the
      toxin than mice immunized with the free monomer P50-75. S and C are more
      effective than P50-75 or the B subunit in increasing the amounts of total IgA
      secreted into the intestine and, moreover, the anti-CT IgA neutralized toxin
      activity. The amounts of anti-CT subclasses (IgG1, IgG2a, IgG2b, and IgG3 plus
      IgM) produced by the antigens depended on how the peptide P50-75 was presented
      for priming to the mice boosted thereafter with the B subunit.

PMID- 7504859
TI  - Two-tag purification of recombinant proteins for the construction of solid matrix
      antibody-antigen (SMAA) complexes as vaccines.
AB  - In order to facilitate the purification of recombinant proteins for immunization
      purposes, for example through the construction of solid matrix-antibody-antigen
      (SMAA) complexes, two small but different tag sequences were attached to the N-
      and C-termini of recombinant proteins. The 12-amino-acid N-terminal tag (His)
      contained an array of six histidines which permitted first-step purification by
      nickel-affinity column chromatography. The C-terminal tag (Pk) was a 14-amino
      acid oligopeptide recognized by the monoclonal antibody (mAb) SV5-P-k. The mAb
      SV5-P-k was linked to a solid matrix and the solid matrix-antibody complexes were
      saturated with PK-linked recombinant antigens to generate SMAA complexes. The
      procedure used for construction of the SMAA complexes also acted as a second
      purification step. Neither of the tag sequences was cleaved from the recombinant
      proteins before immunization. This two-step purification procedure was used to
      construct SMAA complexes containing either p17 or reverse transcriptase (rt) of
      simian immunodeficiency virus (SIV). Mice immunized with these complexes had high
      antibody titres recognizing both the respective recombinant and native SIV
      proteins. A weak antibody response was also measured against both the terminal
      tags. The advantages of using simple dual purification procedures for isolating
      tag-linked recombinant proteins for use in vaccines are discussed.

PMID- 7504860
TI  - [Cytokeratins as markers of differentiation. Expression profiles in epithelia and
      epithelial tumors].
AB  - Intermediate filaments (IFs; diameter, about 10 nm) are cytoplasmic cytoskeletal
      structures found in most vertebrate cells. Their protein subunits comprise a
      large multi-gene family of related proteins, which make it possible to divide IFs
      into seven separate classes whose expression is cell-type-dependent. The most
      important IF classes are cytokeratin (CK) filaments (epithelial cells), vimentin
      filaments (mesenchymal cells), desmin filaments (muscle cells), glial filaments
      (astrocytes), and neurofilaments (nerve cells). As the specificity of expression
      of IF proteins is retained in malignant tumors, they are suitable as histological
      markers of differentiation (tumor markers). The protein subunits of the
      epithelial CK filaments are unusually diverse, and within the various types of
      epithelia, their expression is differentiation specific. Until recently, the
      catalog of human CKs comprised 19 related, yet distinct polypeptides (CKs 1-19;
      Moll et al., 1982a); CK 20 can now be added to this list. On the basis of
      sequence relationships, two CK subfamilies can be delineated (CKs 9-20 = type I;
      CKs 1-8 = type II). Any given epithelial cell exhibits a characteristic,
      differentiation-dependent combination of two or more CK polypeptides, with type-I
      and -II polypeptides always occurring in stoichiometric amounts (i.e., as
      "pairs"), because the basic structural unit of the CK filaments is a
      heterotypical tetramer complex. On the basis of their main tissue distribution
      patterns, it is possible further to subdivide these polypeptides into CKs typical
      of stratified squamous epithelia (CKs 1-6, 9-17) and those typical of simple
      columnar epithelia (CKs 7, 8, 18-20); these CKs exhibit differential expression
      patterns in the various types of squamous and columnar epithelia. The actual
      characterization of the novel CK 20 as a CK initially proved to be rather
      difficult, as this cytoskeletal protein, which can be biochemically isolated from
      cells of the intestinal epithelium (M(r) 46,000; previously called "IT protein"),
      exhibits no reaction with numerous well-known CK antibodies in Western blots.
      However, a series of other characteristics typical of CKs could be demonstrated.
      Thus, IT protein was found, in vitro (nitrocellulose-blot binding test, native
      gel electrophoresis), to for heterotypical complexes with the type-II CK 8, and
      these complexes were able to reconstitute themselves into typical IFs in vitro.
      Chymotrypsin-cleaving experiments revealed the presence of a resistant core
      fragment (M(r) 38,000), indicating a alpha-helical "coiled-coil" conformation
      typical of IFs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7504861
TI  - Intravenous high-dose gammaglobulins for intractable childhood epilepsy.
AB  - Immunological mechanisms have been implicated in the pathogenesis of epileptic
      seizures in some patients and in experimental animal models of epilepsy. A
      beneficial effect of high dose intravenous gammaglobulin (IVIG) has been
      demonstrated for some children with intractable epilepsy. In this study we
      treated 9 children ages 1.1-9.2 years (mean 5.0 years) with intractable epilepsy
      not responsive to conventional antiepileptic drugs (AEDs) and steroid therapy.
      Eight children had Lennox-Gastaut syndrome and 1 had complex partial seizures
      with secondary generalization. Each child received 3 doses of IVIG (200 mg/kg of
      polyvalent immunoglobulin) on Days 1, 15 and 36. Concomitant AEDs were not
      changed. Four children had complete remission, 3 had partial response with a more
      than 50% reduction in seizure frequency and 2 had no response. Onset of response
      varied from immediate to 7 months after the last injection. No toxicity was
      noted. Duration of remission was 9 months in 1 case. The other 3 cases have
      remained in remission to date with a follow up period of 22-26 months. We
      conclude that IVIG is a safe therapy which appears to be effective in some
      children with intractable seizures. Children with shorter duration of their
      seizure disorder (< 1 year) and relatively preserved cognitive function (IQ > 70)
      appear to have a more favorable response. Larger scale controlled trials are
      needed to determine the optimal timing and dosage, as well as to identify
      specific subgroups which may benefit most from IVIG treatment.

PMID- 7504863
TI  - Immunohistochemical and electron microscopic studies of substance P in guinea pig
      nasal glands.
AB  - The distribution of substance P-like immunoreactive (SP-IR) nerve endings in the
      nasal gland of the guinea pig was studied by using histochemical techniques to
      detect mucous glycoprotein and immunohistochemical techniques for SP, in
      combination with electron microscopy. Most nasal glands were negative for both AB
      and periodic acid-Schiff (PAS) staining. The SP-IR nerve fibers were found to
      form a network around these glands. The SP-IR nerve endings were located in the
      region between interdigitated cytoplasmic folds of acinar cells and along the
      cell surface, as well as in the intercellular spaces of proximal ducts. The acini
      which closely contacted with SP-IR nerve endings were serous in type. Our results
      suggest that substance P may contribute to the regulation of serous gland
      secretion in the guinea pig nasal mucosa.

PMID- 7504864
TI  - Ganglionic neurons in vagal and laryngeal nerves projecting to larynx, and their
      peptidergic features in the cat.
AB  - The distribution of cell clusters in the cervical vagal nerve (CVN), superior
      laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN), and the peptidergic
      features of their ganglionic neurons projecting to the larynx, were investigated
      in the cat using a combination of retrograde tracing by wheat germ agglutinin
      (WGA) and immunocytochemistry. In the CVN, a few medium sized cell clusters at a
      level caudal to the nodose ganglion, and some small cell clusters along the
      course of the vagus, were found. In the SLN and RLN, some medium sized ganglia
      were located close to the laryngeal framework and a few small groups of cells
      occupied more rostral parts. Some neurons of the cell clusters in the CVN and
      most of the ganglionic cells in the SLN and RLN exhibited WGA-immunoreactive (IR)
      cells, which projected to the larynx. In these WGA-positive ganglionic neurons,
      many cells showed vasoactive intestinal polypeptide-IR neurons, some neuropeptide
      Y-IR, and a few substance P-IR and calcitonin gene-related peptide-IR cells were
      also identified. The present findings indicate that neurons of the cell clusters
      in the laryngeal nerves, particularly those in the vicinity of the laryngeal
      framework, project to the larynx and may be autonomic.

PMID- 7504862
TI  - Intercrines in brain pathology. Expression of intercrines in a multiple sclerosis
      and Morbus Creutzfeldt-Jakob lesion.
AB  - Expression of cytokine genes regulating vascular permeability and chemoattraction
      was studies by polymerase chain reaction in RNA from two different types of brain
      lesions: a multiple sclerosis plaque and in tissue from a patient with
      Creutzfeldt-Jakob disease. While cytokine genes encoding vascular permeability
      factor, interleukin (IL)-2, IL-4, or IL-10, generally associated with active
      inflammatory processes, were not expressed, we observed expression of some
      intercrine genes in both types of lesions. As these lesions share a common set of
      structural features such as prominent astrogliosis and glial cells are known
      producers of intercrines, we suggest that intercrines have a role in the
      formation of gliotic brain lesions.

PMID- 7504865
TI  - Immunoelectron microscopic studies of synaptic organization in the intralaryngeal
      ganglia of the cat.
AB  - The synaptic organization of nerve terminals containing calcitonin gene-related
      peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P (SP) and
      enkephalin (ENK) in the intralaryngeal local ganglia of the cat was investigated
      by immunoelectron microscopy. CGRP-immunoreactive (IR) and VIP-IR varicose fibers
      formed mainly axo-dendritic synapses, whereas SP-IR and ENK-IR varicose fibers
      made axo-somatic synapses to the principal neurons of the local ganglion. The
      synaptic specializations of the CGRP-IR varicosities were asymmetrical, or Gray's
      type I, whereas the other peptide-IR varicosities showed symmetrical, or Gray's
      type II, synaptic specializations. After denervation of the extrinsic nerves,
      CGRP-IR varicose fibers disappeared from the ganglion, but VIP-IR, SP-IR and ENK
      IR varicose fibers and synapses remained. These results suggest that local
      ganglia act as an integration center of laryngeal function rather than as a
      unidirectional parasympathetic relay center.

PMID- 7504866
TI  - Distributions of the calcitonin gene-related peptide and substance P in the
      monkey larynx.
AB  - The distribution of calcitonin gene-related peptide (CGRP)- and substance P (SP)
      like immunoreactivity in the monkey larynx was studied with light microscopy
      using the immunofluorescence method. We divided the larynx into the following six
      regions: epiglottis, arytenoid region, false cords, ventricle, vocal cords and
      subglottis. The distribution of immunoreactivity in the epithelium and
      subepithelial layer was determined. CGRP- and SP-like immunoreactive nerve fibers
      were observed in all regions of the laryngeal epithelium except in the vocal
      cords. In the epithelium of the epiglottis and arytenoid region, numerous taste
      buds containing several CGRP- and SP-like immunoreactive nerve fibers were
      observed. In the subepithelial layer, CRGP- and SP-like immunoreactive nerve
      fibers were observed in all regions of the larynx. In order of decreasing
      density, these fibers were found in the arytenoid region (especially the
      corniculate tubercle), the epiglottis, the false cords, the subglottis, the
      ventricle, and the vocal cords. In the corniculate tubercle, CGRP- and SP-like
      immunoreactive nerve fibers formed a network, whereas around the cuneiform
      tubercle, dense CRPG- and SP-like immunoreactive nerve fibers were noted parallel
      to the basement membrane. SP-like immunoreactive nerve fibers showed a very
      similar distribution to the CRPG fibers in the epithelium and the subepithelial
      layer, but SP-like fibers were sparser in all regions of the larynx. These
      results, together with previous findings indicate that the arytenoid region and
      the epiglottis of the monkey larynx play very important roles in airway
      protection, swallowing, and respiration.

PMID- 7504867
TI  - Estimation of myocardial damage in Kawasaki disease using antimyosin antibody.
AB  - In a retrospective study, 121 children with Kawasaki disease (KD) were
      investigated to determine (i) the incidence of myocardial damage using the
      antimyosin antibody (AMA) titer; (ii) the differences in the electrocardiograms
      between the AMA-positive and -negative patients; and (iii) the effect of
      treatment with intravenous gamma globulin (IVGG) on the AMA. Comparisons were
      made with 117 normal children (controls). Patients with KD showed a significantly
      higher mean AMA titer and more patients were positive for AMA than the controls.
      The AMA titer in the KD group was not related to the presence of coronary artery
      lesions. Electrocardiograms obtained during the acute and the convalescent stage
      of KD revealed that patients positive for AMA had a significantly lower voltage
      of T wave in lead V6 at week four than at week two of illness, whereas patients
      negative for AMA showed no T wave change after week two. The group treated with
      IVGG showed a significantly lower AMA titer than that not given IVGG. These
      observations suggest that myocardial damage occurs in some patients with KD which
      is unrelated to the presence of coronary artery lesions and that the treatment
      with IVGG reduces the AMA titer in patients with KD.

PMID- 7504869
TI  - Physiological suppression of superoxide dismutase deficiency in yeast
      Saccharomyces cerevisiae.
AB  - Deficiency in superoxide dismutases results in pleiotropic effects including
      hypersensitivity to oxygen and amino acid auxotrophy. Various types of
      physiological suppressors of deficiency in cytosolic superoxide dismutase were
      isolated, whereas attempts to isolate suppressors of mitochondrial enzyme
      deficiency proved a failure. General characteristics of isolated suppressors are
      presented.

PMID- 7504868
TI  - Osteoblasts express the PMCA1b isoform of the plasma membrane Ca(2+)-ATPase.
AB  - We report here that osteoblasts and osteoblast-like osteosarcoma cells express
      PMCA1b, an alternatively spliced transcript of plasma membrane Ca(2+)-ATPase.
      Synthetic oligonucleotide pairs were designed based upon unique regions of the
      cDNA encoding known PMCA isoforms (PMCA1-3) and used as primers in PCR-mediated
      amplification of cDNA synthesized from ROS 17/2.8 osteosarcoma cell RNA. A
      product was observed only when PMCA1-specific primers were present; no products
      were seen with PMCA2 or PMCA3 primers unless cDNA synthesized from rat brain RNA
      was present. Examination of the cDNA encoding the C terminus of PMCA1 from ROS
      17/2.8 cells revealed that the mRNA is spliced to yield the PMCA1b isoform, a
      Ca(2+)-ATPase containing a consensus phosphorylation site for cAMP-dependent
      protein kinase A and a modified calmodulin binding domain. PMCA1b was also
      detected in UMR-106-01 osteosarcoma cells and unpassaged primary rat calvarial
      osteoblasts. These results suggest that the regulation of osteoblast function by
      agents that act via cAMP-mediated pathways may involve alterations in the
      activity of the plasma membrane Ca(2+)-ATPase.

PMID- 7504870
TI  - Different DNA-binding proteins in the primary and secondary forms of Xenorhabdus
      luminescens.
AB  - Basic, heat-stable proteins binding to double-stranded DNA (HASP) were isolated
      from the primary and secondary forms of Xenorhabdus luminescens and their
      composition compared. Two of the proteins with low molecular weight are present
      in both the primary and secondary forms, whereas two others are present only in
      the latter. The described protein fractions may be involved in the regulation of
      transitions between the two forms of X. luminescens.

PMID- 7504872
TI  - Studies on the adaptation of influenza virus replicated at low temperature. V.
      Isoelectric focusing studies.
AB  - Cold adapted variants of influenza viruses replicated at 30 degrees C and 37
      degrees C were tested for isoelectric points (pl's) before and after passages in
      susceptible animals to check the stability of this marker. No differences were
      found in pI's for 3 strains--A/Pol/L/71, A/Phil/2/82 and A/Pol/79/85 which are
      really cold adapted viruses. On the other hand some differences in pI's for other
      strains were observed.

PMID- 7504871
TI  - Comparison of simple methods of methicillin-resistance detection and evaluation
      of some properties of methicillin-resistant Staphylococcus aureus strains.
AB  - Population analysis of methicillin-resistant Staphylococcus aureus and
      determination of their sensitivity to antimicrobial agents were performed. It was
      found, that the methicillin-resistant strains belonged to resistance classes II
      and III. All methicillin-resistant S. aureus were susceptible to ciprofloxacin,
      ofloxacin, vancomycin and teicoplanin. Differences between classes were observed
      in susceptibility to erythromycin and gentamicin.

PMID- 7504873
TI  - Candida valida--a yeast lacking the reverse transsulphuration pathway.
AB  - A new yeast strain PGR-13 was classified as the variant of Candida valida. It is
      unique in its ability to ferment well and ready formation of respiratory
      deficient mutants. The lack of the reverse transsulphuration pathway was found to
      be a common trait of both PGR-13 and the type strain of Pichia membranaefaciens.

PMID- 7504874
TI  - Growth of mycorrhizal fungi in dixenic cultures with bacteria in media of
      different composition.
AB  - Studies were carried out on the effect of bacteria: Arthrobacter globiformis,
      Bacillus subtilis and Pseudomonas fluorescens on biomass production by three
      important ectomycorrhizal fungi: Laccaria laccata, Hebeloma crustuliniforme and
      Rhizopogon vinicolor in media of different composition. It was shown that
      bacteria stimulated, inhibited or did not affect significantly the biomass
      production by mycorrhizal fungi. 3-factor ANOVA have shown that although effect
      of bacteria was statistically significant (p < or = 0.05), composition of medium
      and its pH affected mycelial growth stronger than bacteria.

PMID- 7504875
TI  - Pathogenic effects of Fusarium sulphureum, Fusarium solani Var. coeruleum and dry
      rot affected potatoes on the internal organs of rats.
AB  - Rats of the Wistar race were used in toxicological experiments involving Fusarium
      sulphureum Schl., F. solani var. coeruleum (Sacc.) Booth and potatoes damaged by
      these fungi. The in vivo and postmortem studies revealed that both fungi and
      effected tubers had hepatotoxic and nephrotoxic effects on the animals.
      Morphological changes in the internal organs were mainly manifested by
      disturbances in blood circulation and regressive metamorphosis. These changes
      intensified proportionally to the dose of fungi and diseased potatoes in the feed
      used. Fusarium solani was more pathogenic than F. sulphureum. No teratogenic
      effect was observed, although addition of the fungi and infested potatoes into
      the feeds decreased the reproductive ability of rats and caused a decrease in
      foetal body weight as well as haematomae in foetuses.

PMID- 7504876
TI  - Changes in dehydrogenases activity, number and ultrastructure of mitochondria in
      Aspergillus niger mycelium growing on molasses media.
AB  - Effects of toxic molasses compounds and of the antifoamer (Spumol BJ) on
      dehydrogenases activity, on the number and ultrastructure of mitochondria in A.
      niger mycelium of two strains characterized by different tolerance to toxic
      agents, were observed. In spite of significantly higher dehydrogenases activity
      in the intolerant strain (R-16) mycelia developing both on productive molasses in
      the presence of the defoamer and on non-productive molasses are characterized by
      marked reduction in the activity of these enzymes. Changes in respiratory enzymes
      activity are partly correlated with the number of mitochondria but mostly with
      abnormalities in their ultrastructure.

PMID- 7504877
TI  - The functions of protein surface layers of bacteria.

PMID- 7504878
TI  - Two ways of iron oxidation by yeast.
AB  - It has been found that yeast cells suspended in saline containing ferrous salts
      could oxidize them to the ferric form by excreting H2O2 and ammonia. Excretion of
      ammonia accelerates spontaneous oxidation of iron by molecular oxygen. Ammonia
      generation probably results from the degradation of amino acids within starving
      cells.

PMID- 7504879
TI  - [Scanning electron microscopic findings of the premacular vitreous in eyes
      without posterior vitreous detachment].
AB  - We examined the posterior vitreous of 24 normal autopsy eyes without posterior
      vitreous detachment (PVD) by biomicroscopy and scanning electron microscopy
      (SEM). When the gel component was stained with fluorescein and the specimen was
      immersed in water, the vitreous cortex showed extreme attenuation at the
      premacular area and the lacuna (posterior precortical vitreous pocket: PPVP) was
      present in front of the vitreous cortex. In SEM photographs the same position,
      the vitreous cortex was observed as a cellophane-like membrane overlying the
      retina at the magnification of approximately 40-100 x. The meshwork structure of
      the cellophane-like membrane could be seen at the magnification of approximately
      1,000 x. The size of the fibers forming the mesh was compatible with that of
      vitreous collagen fibers. The smooth surface of internal limiting membrane was
      observed beneath the fibrous membrane. We confirmed that the vitreous cortex was
      present as a fibrous membrane separated from the gel component in eyes with no
      PVD.

PMID- 7504880
TI  - Comparison of the effects of amiodarone versus metoprolol on the frequency of
      ventricular arrhythmias and on mortality after acute myocardial infarction. SSSD
      Investigators. Spanish Study on Sudden Death.
AB  - A randomized trial was conducted to assess the efficacy of amiodarone versus
      metoprolol or no antiarrhythmic treatment to suppress asymptomatic ectopic
      activity and improve survival in patients who have had myocardial infarction with
      a left ventricular ejection fraction of 20 to 45% and > or = 3 ventricular
      premature complexes per hour (pairs or runs). Patients (n = 368) were randomly
      assigned to receive amiodarone 200 mg/day (n = 115) 10 to 60 days after the acute
      episode, and metoprolol 100 to 200 mg/day (n = 130) or no antiarrhythmic therapy
      (n = 123). After a median follow-up of 2.8 years, mortality in the amiodarone
      treated patients (3.5 +/- 2% SEM) did not differ significantly from that of
      untreated control subjects (7.7 +/- 2.5%, p = 0.19), but was lower than that in
      the metoprolol group (15.4 +/- 3.5%, p = 0.006). Patients treated with metoprolol
      had twice the mortality seen in control subjects, even though the differences
      were not statistically significant. Holter studies performed at 1, 6 and 12
      months showed that both amiodarone and metoprolol were equally effective in
      reducing heart rate, whereas only amiodarone significantly reduced ectopic
      activity (p < 0.0001). Thus, long-term treatment with amiodarone was clearly safe
      in patients with an ejection fraction of 20 to 45%, was effective in suppressing
      arrhythmias, and was associated with a lower mortality than metoprolol;
      corroboration is required in a larger trial.

PMID- 7504881
TI  - Congenital contractures, ectodermal dysplasia, cleft lip/palate, and
      developmental impairment: a distinct syndrome.
AB  - Brothers were affected with severe congenital contractures, multiple cutaneous
      manifestations of ectodermal dysplasia, cleft lip/palate, and psychomotor and
      growth impairment. High resolution prometaphase chromosomes were normal.
      Molecular studies of DNA markers, closely flanking the X-linked hypohidrotic
      ectodermal dysplasia locus, did not show evidence of a submicroscopic deletion
      from the Xq12-q13 region. The parents and a normal sister exhibited none of these
      findings. This constellation of anomalies appears to represent a unique AR or XLR
      syndrome.

PMID- 7504882
TI  - Tetrasomy 5p mosaicism in a boy with delayed growth, hypotonia, minor anomalies,
      and an additional isochromosome 5p [46,XY/47,XY, + i(5p)].
AB  - We describe a 1-year-old boy with a rare de novo 46,XY/47,XY, + i(5p) mosaicism
      (ratios 28/3 in peripheral blood lymphocytes and 2/12 in skin fibroblasts). The
      boy, born after a pregnancy of 34 weeks, had lung hypoplasia, persistent
      hypotonia, and postnatal growth failure. Craniofacial anomalies were also
      present. His clinical manifestations correspond to those described in trisomy 5p
      patients. Prenatal diagnosis on maternal age indication had shown normal male
      chromosomes in 16 cells in the short term culture of a chorionic villus sampling.
      Retrospectively, 1 out of 217 cells in this culture showed the i(5p). Several
      mechanisms could have resulted in the formation of this 46/47, + i(5p) mosaic.
      Postzygotic local incorrect ligation during chromatid replication, followed by a
      second replication offers an attractive model on theoretical grounds since it
      needs only one step to explain both isochromosome formation and mosaicism.
      Differences between the various tissues in selection pressure on cells with the
      isochromosome might explain the different ratios of mosaicism found.

PMID- 7504883
TI  - Inducible expression of vascular cell adhesion molecule-1 by vascular smooth
      muscle cells in vitro and within rabbit atheroma.
AB  - Vascular cell adhesion molecule-1 (VCAM-1), a mononuclear leukocyte adhesion
      molecule, is expressed in cultured vascular endothelial cells activated by
      cytokines and is induced in rabbit aortic endothelium in vivo within 1 week after
      initiation of an atherogenic diet. We now demonstrate that vascular smooth muscle
      cells can also express VCAM-1 in rabbit atherosclerotic lesions in vivo and in
      response to cytokines in vitro. Immunohistochemical staining of aortas from
      rabbits fed a 0.3% cholesterol-containing diet revealed that a portion of smooth
      muscle cells within intimal foam cell-rich lesions expressed VCAM-1. The intimal
      VCAM-1-expressing cells localized predominantly in regions above the internal
      elastic lamina. These VCAM-1-positive cells had the typical spindle shape of
      smooth muscle cells but had reduced alpha-actin expression in comparison to
      normal medial smooth muscle cells, and did not bear markers for endothelium,
      macrophages, and T cells. In culture, rabbit aortic smooth muscle cells expressed
      VCAM-1 mRNA and protein in a time- and concentration-dependent fashion when
      exposed to interferon-gamma or Gram-negative bacterial lipopolysaccharide.
      Cultured human vascular smooth muscle cells also expressed VCAM-1 mRNA and
      protein in response to lipopolysaccharide, interferon-gamma, and interleukin-4.
      The monokines interleukin-1 alpha and tumor necrosis factor-alpha did not induce
      VCAM-1 expression in either rabbit or human vascular smooth muscle cells.
      Inducible VCAM-1 expression by vascular smooth muscle cells in vivo during
      hypercholesterolemia and in vitro in response to certain cytokines suggests a
      broader range of VCAM-1 functions in vascular biology than heretofore
      appreciated.

PMID- 7504884
TI  - Melanocyte lineage-specific antigens recognized by monoclonal antibodies NKI
      beteb, HMB-50, and HMB-45 are encoded by a single cDNA.
AB  - The glycoproteins recognized by monoclonal antibody (MAb) NKI-beteb are among the
      best diagnostic markers for human melanoma. MAb NKI-beteb reacts with melanoma
      cells throughout tumor development and does not cross-react with other tumor or
      normal cells, except for cells of the melanocytic lineage. Two other melanocyte
      lineage-specific MAbs, HMB-50 and HMB-45, show a specificity and staining pattern
      strikingly similar to the ones observed for NKI-beteb. Herein, we demonstrate
      that all three MAbs recognize protein products encoded by a single cDNA.
      Expression of this cDNA in BLM cells results in immunoreactivity with all three
      MAbs. In addition, we demonstrate co-distribution of the RNA species detected by
      the cDNA with the proteins recognized by the MAbs in tissue sections.

PMID- 7504885
TI  - Immunocytochemical evidence that the beta-protein precursor is an integral
      component of neurofibrillary tangles of Alzheimer's disease.
AB  - Amyloid beta (A beta) immunoreactivity has been demonstrated in all extracellular
      neurofibrillary tangles (E-NFT) and most intraneuronal neurofibrillary tangles (I
      NFT). We undertook this immunocytochemical study to understand the relationship
      between A beta immunoreactivity localized in NFT and beta-protein precursor (beta
      PP). We found epitopes of amino-, mid-, and carboxyl-terminal domains of beta PP
      in I-NFT and the majority of E-NFT. NFT retained beta PP after ionic detergent
      extraction, demonstrating that beta PP is an integral component of NFT. Finding
      beta PP in regions of A beta immunoreactivity raises the possibility that beta PP
      or its fragments associate with amyloid, and that the stability of A beta is
      responsible for its dominance in amyloid deposits.

PMID- 7504886
TI  - Activation, proliferation, and differentiation of progenitor cells into
      hepatocytes in the D-galactosamine model of liver regeneration.
AB  - Rat liver regeneration was studied from 24 hours to 8 days after a single
      intraperitoneal injection of D-galactosamine (GalN). Morphological changes in the
      liver were analyzed in parallel with sequential changes in expression of histone
      3 mRNA (a marker of cell proliferation), fetal alpha-fetoprotein (AFP) mRNA and
      gamma-glutamyl transpeptidase (GGT) (markers of fetal hepatocytes), and albumin
      mRNA and glucose-6-phosphatase (G6Pase) (markers of adult hepatocytes).
      Proliferation of nonparenchymal epithelial cells (NPC), detected in situ by
      [3H]thymidine labeling or histone-3 mRNA expression, began after 24 hours
      primarily in the portal area around the bile ducts. After 2 days, histone-3
      labelling intensity increased in rows and clusters of NPC which expanded from the
      portal zone and invaded into the parenchyma. On days 3 and 5, NPC expressing his
      3 mRNA expanded further, forming pseudo-ducts and islet-like structures (NPC
      structures). Proliferating NPC were positive for GGT. Some GGT positive cells
      were also positive for the fetal form of AFP mRNA, which lagged behind GGT by 24
      hours and peaked on day 5. On day 3, some cells with the appearance of NPC
      expressed albumin mRNA. Double label in situ hybridization for fetal AFP and
      albumin mRNAs and dual histochemistry for GGT and G6Pase showed simultaneous
      expression of these markers in NPC on day 5. Other cells expressing fetal AFP
      mRNA or GGT on day 5 had a morphological appearance between NPC and hepatocytes
      (transitional cells). Proliferation of hepatocytes began on day 2, reached
      maximum on day 5 and then declined. Proliferating hepatocytes did not express
      fetal AFP mRNA or GGT. These findings indicate that after GalN injury, the liver
      responds by activation of progenitor cells that proliferate and then
      differentiate into mature hepatocytes. Adult hepatocytes can also proliferate
      after GAlN injury, but these hepatocytes do not undergo
      dedifferentiation/redifferentiation during regeneration of the hepatic lobule.

PMID- 7504887
TI  - Type I collagen gene expression in human atherosclerosis. Localization to
      specific plaque regions.
AB  - Because collagen is a major component of the human atherosclerotic plaque,
      factors controlling collagen synthesis may have a profound influence on the
      volume growth of these intimal lesions. In human arteries, we compared normal vs
      atherosclerotic media vs intimas for type I collagen gene expression using
      immunocytochemistry and in situ messenger RNA hybridization with subsequent
      correlations with plaque topographical features. We also determined the
      associations of such collagen gene expression with proximity to
      monocyte/macrophages and T lymphocytes. Type I collagen synthesis appears to be
      upregulated in atherosclerotic plaques compared with their underlying medias and
      normal internal mammary arteries and coronary diffuse intimal thickenings. At
      least in established and advanced coronary and carotid plaques, type I collagen
      gene expression is focal and especially prevalent in fibrous cap and vascularized
      regions. Although macrophages and type I procollagen messenger RNA and protein
      are both found in atherosclerotic plaques, no apparent spatial correlation
      between macrophage presence and type I procollagen presence was found within
      these atherosclerotic intimas. Type I procollagen presence appears to be
      negatively associated with the spatial presence of T cells. Thus, human
      atherosclerotic plaques exhibit nonuniform patterns of type I collagen gene
      expression. Although the biochemical determinants of this focal gene expression
      have yet to be determined, it is conceivable that stimulatory/inhibitory
      cytokines and other factors (eg hemodynamics) play important roles in determining
      the focal nature of collagen synthesis in atherosclerosis.

PMID- 7504889
TI  - Tumor necrosis factor activates human endothelial cells through the p55 tumor
      necrosis factor receptor but the p75 receptor contributes to activation at low
      tumor necrosis factor concentration.
AB  - Tumor necrosis factor-alpha (TNF-alpha) interacts with two distinct membrane
      receptor proteins, p55 and p75, which are variably expressed on different cell
      types. We have examined the function of p55 and p75 on human endothelial cells
      (EC). Both receptor types are detected on cultured EC by FACS analysis. A
      mutagenized recombinant human TNF (R32W-TNF), which binds selectively to p55, is
      equipotent with human recombinant wild-type TNF (wt-TNF) in upregulating several
      different leukocyte adhesion molecules as well as class I major
      histocompatibility complex molecules. R32W-TNF also fully desensitizes EC to wt
      TNF, as assessed by inhibition of re-induction of endothelial leukocyte adhesion
      molecule-1 (ELAM-1). At low wt-TNF concentrations, induction of ELAM-1 is partly
      inhibited by blocking monoclonal antibodies to either p55 or p75 and to a greater
      extent by a combination of both monoclonal antibodies. In contrast, ELAM-1
      induction by R32W-TNF is only inhibited by anti-p55. We conclude that both TNF
      receptors (p55 and p75) can contribute to TNF-induced activation of EC, but that
      signaling through p55 is sufficient.

PMID- 7504888
TI  - Keratin 17 expression as a marker for epithelial transformation in viral warts.
AB  - The profile of keratin expression in benign warts from various cutaneous and
      mucosal sites along with dysplastic warts and squamous cell carcinomas has been
      examined using a panel of monospecific antibodies to epithelial keratins. Viral
      warts and verrucous keratoses from immunosuppressed renal transplant recipients
      show a spectrum of squamous atypia from benign lesions, from minimal changes to
      full thickness dysplasia. Changes associated with malignancy include loss of
      differentiation-specific keratins 1 and 10 together with expansion of basal cell
      epitopes and inappropriate expression of simple epithelial keratins 8, 18, and 19
      in advanced squamous cell carcinoma. This late expression of keratins 8 and 18
      contrasts with early expression of keratin 17 in all dysplastic lesions examined.
      Keratin 17 is found suprabasally in hyperproliferative lesions, including benign
      warts, but marked basal plus suprabasal expression is seen increasingly in
      malignantly transformed epidermis. These findings were not specific to
      immunosuppression, as shown by identical findings in control squamous cell
      carcinoma from nonimmunosuppressed individuals. Keratin 17 expression may prove
      prognostically helpful when assessing dysplasia in epidermal tumors.

PMID- 7504890
TI  - Rat alveolar myofibroblasts acquire alpha-smooth muscle actin expression during
      bleomycin-induced pulmonary fibrosis.
AB  - The majority of fibroblasts in alveolar septa are characterized by the presence
      of cytoplasmic bundles of microfilaments that contain cytoplasmic actin isoforms;
      these cells have been named contractile interstitial cells or V-type
      myofibroblasts. In the rat, they express desmin as intermediate filament protein.
      In this study, we explored the possibility that modulation and replication of
      such septal fibroblasts result in the appearance of alpha-smooth muscle (alpha
      SM) actin-positive myofibroblasts, typical of lung fibrosis. Experimental
      pulmonary fibrosis was produced by a unique intratracheal instillation of
      bleomycin to 28 rats. Eight additional rats used as controls received the
      equivalent volume of saline. Paraffin and frozen sections of lungs were examined
      at days 1, 3, 5 and 7 after treatment. Microfilaments and intermediate filaments
      were stained using antibodies against total actin, alpha-SM actin, desmin,
      vimentin, keratin, and SM myosin. Electron microscopic labeling of desmin and
      alpha-SM actin using immunogold technique was done on Lowicryl K4M resin-embedded
      specimens. alpha-SM actin appeared in desmin-positive alveolar fibroblasts as
      early as 24 hours after intratracheal bleomycin instillation; the modulation of
      alpha-SM actin in these cells was preceded by a lymphomonocytic infiltration of
      alveolar septa. Twenty-four hours to 3 days after bleomycin administration, a
      proliferation of alveolar myofibroblasts occurred. Fibrosis with laying down of
      collagen fibers took place after the above mentioned cellular modifications. Our
      results support the view that septal fibroblastic cells can modulate into typical
      alpha-SM actin-containing myofibroblasts during experimental bleomycin-induced
      pulmonary fibrosis. In such a modulation a possible role of cytokines,
      particularly of transforming growth factor-beta, is considered.

PMID- 7504892
TI  - Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of
      asthma.
AB  - To investigate the role of IL-5 in airway hyperreactivity and pulmonary
      eosinophilia, we used a model of allergic asthma in guinea pigs and a
      neutralizing monoclonal antibody (TRFK-5) directed against murine IL-5.
      Sensitized guinea pigs were challenged with 1% ovalbumin (OVA) aerosol and
      assessed for airway eosinophilia (by bronchoalveolar lavage [BAL] and histologic
      evaluation of airway tissue) and bronchoconstrictor responsiveness to substance P
      (SP) (as RL100 and Cdyn40) 24 h later. OVA challenge of sensitized animals caused
      a significant increase in airway responsiveness to SP, with a 4.9-fold decrease
      in RL100 and a 4.7-fold decrease in Cdyn40. Accompanying this increased
      sensitivity to SP was a 9-fold increase in eosinophils recovered in BAL and a 4-
      to 5-fold increase in eosinophils in intrapulmonary bronchial tissue.
      Intraperitoneal treatment with 10 mg/kg of the IL-5 antibody 2 h before OVA
      challenge blocked BAL and lung tissue increases in eosinophils but had no effect
      on the development of airway sensitivity to SP. In contrast, similar treatment
      with 30 mg/kg of this antibody blocked OVA-induced increased sensitivity to SP as
      well as BAL and lung tissue eosinophilia. These data suggest a critical and
      possibly independent role for IL-5 in allergic airway hyperresponsiveness and the
      accumulation of eosinophils within the lung of the guinea pig.

PMID- 7504893
TI  - Evidence for substance P as an endogenous substance causing cough in guinea pigs.
AB  - We examined an endogenous substance causing cough in awake guinea pigs. An
      intraperitoneal injection of phosphoramidon, a selective inhibitor of neutral
      endopeptidase (E.C. 3.4.24.11), caused cough in a dose-dependent fashion for
      approximately 40 min. At a dose of 3 x 10(-3) mol/kg, phosphoramidon caused a
      total of 11.6 +/- 1.4 coughs in 40 min. Phosphoramidon (3 x 10(-3) mol/kg)
      induced cough was significantly inhibited by systemic pretreatment with capsaicin
      (p < 0.01). Aerosols of FK 888 (1 min), a specific inhibitor of substance P (NK1)
      receptor, inhibited phosphoramidon (3 x 10(-3) mol/kg)-induced cough in a dose
      dependent fashion with complete inhibition at a dose of 10(-5) M. Likewise,
      aerosols of FK 224 (10(-5) M; 1 min), another inhibitor of NK1 and NK2 receptors,
      or lidocaine (4%, 1 min) significantly inhibited phosphoramidon (3 x 10(-3)
      mol/kg)-induced cough (p < 0.01). Furthermore, aerosols of FK 888 (10(-5) M; 1
      min) significantly inhibited cough induced by cigarette smoke in awake guinea
      pigs (p < 0.01). These results suggest that substance P released from sensory
      nerves in the airway may be an endogenous substance causing cough and the
      substance P antagonist may be the drug for treatment of cough in respiratory
      disease.

PMID- 7504894
TI  - Idiopathic pulmonary fibrosis and hepatitis C virus infection.
AB  - A possible role for hepatitis C virus (HCV) infection in the pathogenesis of
      idiopathic pulmonary fibrosis (IPF) has recently been suggested on the basis of
      an unusually high seroprevalence rate of anti-HCV in such patients from Japan. In
      an attempt to confirm these findings, we tested sera from 62 patients with IPF by
      two second-generation anti-HCV ELISAs. Only one serum was reactive. Serum from
      this patient gave an indeterminate result when tested by four-antigen RIBA (c22
      band only), and it was negative for the presence of HCV RNA when tested by the
      reverse transcriptase polymerase chain reaction assay. HCV infection is thus no
      more prevalent in patients with IPF from the UK than in the general population.

PMID- 7504891
TI  - Effects of in utero exposure to street drugs.

PMID- 7504895
TI  - The integrin alpha 4 beta 1 and its counter receptor VCAM-1 in development and
      immune function.
AB  - The integrin alpha 4 beta 1 and its counter receptor vascular cell adhesion
      molecule-1 (VCAM-1) mediate well-described cell-cell interactions that are
      critical for immune function. However, these receptors also mediate cell-cell
      interactions that are important for skeletal muscle differentiation. We have
      found that contrasting transcriptional mechanisms control their patterns of
      expression in the immune system and in muscle. Recent studies indicate that alpha
      4 beta 1 and VCAM-1 are also expressed in a number of developing tissues,
      implying that these receptors have a general role in facilitating cell-cell
      interactions during development.

PMID- 7504897
TI  - Adhesion molecules in allergic inflammation.
AB  - Allergic inflammation is characterized by recruitment of specific leukocyte
      subpopulations from blood into tissue and requires a series of cell adhesion
      molecule-mediated interactions between postcapillary vascular endothelium and the
      leukocyte cell surface. Three major groups are involved: selectins, integrins,
      and the immunoglobulin gene superfamily. P- and E-selectin mediate initial
      leukocyte adhesion, whereas beta 2-integrin/ICAM-1 and VLA-4/VCAM-1 pathways
      mediate leukocyte arrest and transendothelial migration. Because VLA-4 expression
      is restricted to eosinophils and lymphocytes, VCAM-1 has been implicated in
      selective eosinophil recruitment characterizing allergic inflammation. However,
      additional factors such as profile of cytokine release are likely to operate
      since tissue eosinophilia has been observed in the absence of VCAM-1 expression.
      Recent use of monoclonal antibodies against functional epitopes on various cell
      adhesion molecules in animal models of extrinsic allergic asthma offers new
      possibilities in management of allergic disease.

PMID- 7504896
TI  - Regulation of tissue-selective T-lymphocyte homing receptors during the virgin to
      memory/effector cell transition in human secondary lymphoid tissues.
AB  - Conventional virgin T cells efficiently and homogeneously recirculate through all
      secondary lymphoid tissues, but not "extralymphoid" effector sites. In contrast,
      memory/effector populations are composed of distinct subsets with differential,
      often tissue-selective, migratory capability to both secondary lymphoid tissues
      and effector sites. In keeping with these observations, CD45RA(high)/RO(low)
      virgin T cells in human peripheral blood uniformly express the peripheral lymph
      node (PLN) homing receptor (HR) L-selectin, and lack the skin-selective HR CLA,
      whereas among the CD45RA(low)/RO(high) "memory/effector" population, differential
      expression of these HR yields three predominant subsets: L-selectin+/CLA+, L
      selectin+/CLA-, L-selectin-/CLA-. Although these subsets are of approximately
      equal size in the peripheral blood, the vast majority of T cells obtained from
      cutaneous chronic inflammatory sites display the L-selectin+/CLA+ phenotype. To
      investigate the mechanisms responsible for the generation of these
      memory/effector T-cell subsets, we developed a multiparameter flow cytometric
      technique that defines a common pathway of postthymic T-cell differentiation in
      secondary lymphoid tissues: the virgin to memory/effector transition. Our
      analyses indicate that these HR are differentially regulated during the virgin to
      memory/effector transition in a tissue-specific fashion. The great majority of
      memory/effector T cells produced in PLN retain high levels of L-selectin
      expression, and 50 to 60% upregulate CLA. In contrast, memory/effector T cells
      produced in appendix and tonsil are generally L-selectin(low), and CLA is
      upregulated on less than 10% of newly formed memory/effector T cells in appendix
      and on about 30 to 35% of such cells in tonsil.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504898
TI  - [Pediculosis capitis: a questionnaire survey in 4 schools of the Bordeaux Academy
      1990-1991].
AB  - A questionnaire survey of head lice treatment was conducted in four schools--each
      including a nursery and an elementary school--in the Bordeaux area. Two schools
      were situated in the centre of the city, one in a suburban area and one in a
      rural area (50 km from the city). Four-page questionnaires were filled in
      anonymously by the parents in April 1991; 840 answers were obtained (80 p. 100
      response rate). Between January 1990 and March 1991, 48.7 p. 100 of children had
      at least one episode of head lice infestation (infestation rates varied from 38.8
      to 62.6 p. 100 depending on the schools); 30.5 p. 100 of children were
      contaminated for the first time during that period. Lice were detected by the
      parents in 95 p. 100 of the cases. The prevalence of lice was higher in females
      (60 p. 100) than in males (40 p. 100). The highest prevalence was noted in the
      suburban school where 17 p. 100 of the parents were unemployed at the time of the
      survey. The peak age for head lice was 7, but 19.4 p. 100 of nursery school
      children aged 2-4 years had been contaminated at least once. Impetigo was rare
      (1.2 p. 100), and pruritus was noted in only 14.2 p. 100 of the cases. Most
      children had been contaminated at school. Curative treatment was counselled by a
      chemist in 87 p. 100 of the cases. Pyrethrins were used in 81 p. 100, and the
      shampoo (Hegor) plus spray (Paraspecial Poux) association was the most frequent,
      totalling two-thirds of prescriptions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504900
TI  - Selection of patients for surgery in the management of thyrotoxicosis.
AB  - There is at present no consensus as to what the best treatment for thyrotoxicosis
      is. If the patients are carefully selected, surgery offers a safe and effective
      cure for the disease over a short period of time. We reviewed the selection
      criteria of forty-one patients with thyrotoxicosis treated surgically in
      Alexandra Hospital. Over 90% of the patients were referred for surgery by
      physicians and general practitioners. The majority (95%) were young patients
      (under 40 years) and almost all were treated with antithyroid drugs before opting
      for surgery. The most common indication given for surgery was failure of
      conservative treatment (20/41). This was followed by patients who had difficulty
      adhering to the antithyroid drug regime (12/41) and patients who requested
      surgery for cosmetic reasons (5/41). Almost half of the patients had large glands
      (> 50g). One year after surgery, 84% of the patients remained euthyroid, 8%
      developed hypothyroidism and 8% had relapsed thyrotoxicosis. Three quarters of
      the patients tested positive for thyroid antibodies. This did not appear to
      increase the rate of hypofunction. There was no mortality from surgery.

PMID- 7504899
TI  - [Small intestine transplantation. Experimental and clinical results].
AB  - The intestine was one of the first organs to be successfully transplanted
      experimentally. Results in humans were disappointing until recently, partly due
      to the large quantity of lymphoid tissue present in the intestine, resulting in a
      vigorous rejection process which is difficult to control. Recent advances in
      experimental studies have improved our knowledge about mechanisms of rejection
      and graft-versus-host disease, and have allowed the development of new
      immunosuppressive therapies. At the present time, major obstacles remain in
      clinical intestinal transplantation (i.e. difficulty of preventing rejection
      despite massive immunosuppression, high rate of postoperative sepsis). However,
      the protective effect of a concomitant transplanted liver and the use of FK 506
      have allowed a dramatic improvement in clinical results, justifying continuation
      of experimentation of intestinal transplantation in humans.

PMID- 7504901
TI  - Usefulness and limitations of thyrotropin measurements as a first-line test for
      follow-up of Graves' patients.
AB  - We evaluated the usefulness of sensitive thyrotrophin hormone (TSH) measurements
      in determining the thyroid status in the follow-up of Graves' patients undergoing
      medical treatment with thionamides. Out of a total of 186 serum samples tested,
      TSH levels were suppressed in 123 (66.1%), normal in 32 (17.2%) and elevated in
      31 (16.7%) cases. Total T4, or T3 or both were elevated only in 97 (74.8%) cases
      of TSH-suppressed patients, indicating that TSH is less discriminatory as a first
      line test for patients under treatment due to the hypothalamic-pituitary lag
      period. No comparisons with free T4 or free T3 were done in this study. Both
      total T4 (120 +/- 28 nmol/l) and TBII (23 +/- 21%) levels were significantly
      greater (p < 0.02) in the euthyroid group with suppressed TSH. This may suggest
      that persistence of a thyrotoxic state may still be present.

PMID- 7504902
TI  - Examining the therapeutic options in hyperthyroidism--a personal perspective.
AB  - After confirmation of the diagnosis of hyperthyroidism, an aetiological clue
      should be ascertained. Any therapy should be directed toward the primary
      aetiology and should weigh the risk-benefit ratio carefully. Transient thyrotoxic
      states like thyroiditis may be treated with beta blockers, provided no
      contraindications exist. Beta blockers may also be used to treat the sympathetic
      symptoms and the response is usually rapid. The general trend is to use
      antithyroid drugs as first-line therapy, although relapses are the commonest
      problems with antithyroid drugs. Thionamides are the most common drugs used to
      treat the thyrotoxic state. Thionamides used in high doses have immunomodulatory
      effects and these effects can be utilised to reduce the risk of relapses in
      Graves' thyrotoxicosis. Iodides are usually reserved in the preoperative
      preparations of patients. Surgery, unlike medical therapy or radioiodine, can be
      offered as a therapeutic alternative only once. It may be offered where medical
      therapy has failed, where patients develop antithyroid drug allergies, and where
      the goitre causes obstructive symptoms or is of cosmetic concern. Prior to
      surgical therapy, adequate preparation should be obligatory. It is preferable to
      achieve clinical and biochemical euthyroidism prior to surgery. The use of
      radioiodine in therapeutics has become more acceptable and established. Although
      safe, it has the major drawback of cumulative hypothyroidism. There is still
      debate on the use of radioiodine in children. In 1989, the incidence of
      peritonitis was one episode every 24 patient-month which was significantly lower
      than the general population on CAPD of one episode every 17 patient
      month.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504903
TI  - Neural mechanisms of joint pain.
AB  - Joint pain is a common symptom in various forms of arthritis. Unfortunately, the
      mechanisms involved in the pathogenesis of joint pain are not well understood,
      but probably include peripheral and central neural mechanisms. The sympathetic
      system appears to interact with sensory afferents under pathological conditions,
      and this may be mediated directly via receptors on sensory neurons, or indirectly
      via inflammatory mediators. Classical inflammatory mediators such as serotonin
      and bradykinin appear to activate some nociceptive afferents and serotonin may
      sensitise these afferents to non-noxious stimuli in an inflamed joint. A purely
      sensory function has traditionally been ascribed to sensory afferents, but
      unmyelinated C fibres have in addition a neurosecretory role and release peptides
      such as substance P which may contribute to inflammation. Lastly, central
      sensitisation in the spinal cord may play an important role in the pathogenesis
      of joint pain. Activation of N-Methyl-D-Aspartate (NMDA) receptors and the wind
      up phenomenon may be involved in central sensitisation.

PMID- 7504905
TI  - Regulation of the heat-shock response in bacteria.
AB  - When bacteria cells are exposed to higher temperature, a set of heat-shock
      proteins (hsps) is induced rapidly and transiently to cope with increased damage
      in proteins. The mechanism underlying induction of hsps has been a central issue
      in the heat-shock response and studied intensively in Escherichia coli.
      Immediately upon temperature upshift, the cellular level of sigma 32 responsible
      for transcription of heat-shock genes increases rapidly and transiently. The
      increase in sigma 32 results from both increased synthesis and stabilization of
      sigma 32, which is ordinarily very unstable. A clue to further understanding of
      early regulatory events came from recent analysis of translational induction and
      subsequent shut-off of sigma 32 synthesis. Whereas a 5'-coding region of mRNA for
      sigma 32 is involved in the induction mediated by the mRNA secondary structure, a
      distinct segment of sigma 32 polypeptide further downstream is involved in the
      DnaK/DnaJ-mediated shut-off and destabilization of sigma 32 that may be mutually
      interconnected.

PMID- 7504904
TI  - ATP-dependent transport systems in bacteria and humans: relevance to cystic
      fibrosis and multidrug resistance.
AB  - The prokaryotic permeases are members of a superfamily of membrane transporters
      called traffic ATPases, which includes the medically important eukaryotic
      multidrug resistance (MDR) protein and cystic fibrosis transmembrane regulator
      (CFTR). Members of this superfamily have extensive sequence and structural
      similarity, in particular in an ATP-binding motif, and are believed to use ATP to
      energize translocation of substrates across biological membranes. The prokaryotic
      histidine permease is well-characterized and serves as a convenient model system.
      In this review, we highlight some of the biochemical and molecular biological
      approaches used to study the functional and architectural organization of this
      permease and relate the results of these approaches to what is known about other
      traffic ATPases. We have identified specific regions that we believe critical for
      the function of the histidine permease and propose that the corresponding regions
      in the eukaryotic traffic ATPases are also important for their function. In light
      of the fact that CFTR (and possibly the MDR protein) is an ion channel, we
      compare the properties of channels and transporters; in addition, we discuss the
      possibility that other members of the traffic ATPases may also have channel-like
      activity.

PMID- 7504906
TI  - Genetics of differentiation in Streptomyces.
AB  - The use of mutants and molecular genetics has begun to reveal how differentiation
      is brought about in multicellular, mycelial Streptomyces spp. Alternative
      pathways to aerial mycelium formation may be activated on different media. In
      some cases, extracellular signals are transmitted or exchanged. Extracellular
      proteins may act as morphogens in the erection of aerial hyphae. A rare codon,
      UUA, is apparently confined to mRNAs from a few genes important only for early
      stages of differentiation; it is absent from vegetative or developmentally late
      mRNAs. Sporulation of aerial hyphae involves at least four specific regulatory
      proteins, including a sigma factor and an unusual small protein. A complex
      interplay between the sporulation regulatory genes, rather than a simple linear
      dependence cascade, is emerging.

PMID- 7504907
TI  - The Tn5 transposon.
AB  - The bacterial transposon Tn5 encodes two proteins, the transposase and a related
      protein, the transposition inhibitor, whose relative abundance determines, in
      part, the frequency of Tn5 transposition. The synthesis of these proteins is
      programmed by a complex set of genetic regulatory elements. The host DNA
      methylation function, dam, inhibits transposase promoter recognition and
      indirectly enhances the transposition inhibitor promoter. The inhibitor lacks the
      N-terminal 55 amino acids of the transposase, suggesting that this sequence plays
      a key role in the transposition process. An intact N-terminal sequence is
      required for the transposase's recognition of the 19-bp end DNA sequences. This
      is the first critical step in the transposition process. Transposase-end DNA
      interaction is itself regulated by an intricate series of reactions involving
      several host proteins: DnaA, Dam, and Fis. The transposase is a unique protein in
      that it acts primarily in cis and inhibits its own activity in trans. Models to
      explain these properties are described. Finally circumstantial evidence suggests
      that transposition occurs preferentially from newly replicated DNA that has yet
      to be partitioned to progeny cells. This timing of transposition is likely to
      have a selective advantage for the host and the transposable element.

PMID- 7504908
TI  - Infectious amplification of wild-type human immunodeficiency virus from patients'
      lymphocytes and modulation by reverse transcriptase inhibitors in vitro.
AB  - The relative in vitro potency of nine human immunodeficiency virus (HIV) type 1
      reverse transcriptase inhibitors was evaluated in a coculture assay which
      measures the frequencies of infectious primary cells from HIV-positive patients
      by the limiting dilution technique and measures their apparent reduction under
      increasing concentrations of drugs. An advantage of this assay is that it
      utilizes a variety of wild-type viruses not selected by in vitro propagation.
      Potency ranking placed the (-)-L-enantiomer of 2',3'-dideoxy-5-fluoro-3'
      thiacytidine [(-)-FTC], an oxathiolane pyrimidine nucleoside analog (90%
      effective concentration = 55 nM), before 2',3'-dideoxycytidine (DDC) (74 nM), (-)
      2',3'-dideoxy-3'-thiacytidine (3TC) (300 nM), 3'-azido-3'-deoxythymidine (AZT)
      (530 nM), TIBO R82913 (670 nM), and 2',3'-dideoxyinosine (DDI) (6,400 nM). HIV
      from AZT-naive patients' lymphocytes was more sensitive to the inhibitory effect
      of (-)-FTC, 3TC, or DDC than was highly AZT-resistant HIV obtained from AZT
      treated patients' cells, indicating partial cross-resistance between thymidine
      and cytidine analogs. Combined inhibitory concentrations of AZT with (-)-FTC,
      3TC, DDC, and DDI produced synergistic interactions as determined by the multiple
      drug effect analysis. Synergistic interactions were demonstrable with AZT plus (
      )-FTC or with AZT plus DDC with cells bearing AZT-resistant HIV. The inhibitory
      concentrations of AZT established by this cell-to-cell virus transmission assay
      are closer than those determined by the conventional assay system to the
      extracellular AZT concentrations required in patients' plasma to achieve
      comparable levels of HIV inhibition in vivo.

PMID- 7504910
TI  - The AORN Audiovisual Committee. Thirty-three years of perioperative nursing
      education.
AB  - The productions of the AORN Audiovisual Committee are best measured by their
      popularity. Enthusiastic audiences at Congress premieres and demands for bookings
      by chapters and individual instructors represent thousands of viewers for each
      film. A complete list of all films produced by the Committee is available in the
      archives, located in the AORN library at Headquarters. Readers may obtain a
      complete list of all perioperative nursing film topics produced by this program
      in the past 33 years from the author. The out-of-pocket costs for producing these
      films and videotapes during the past 33 years exceeds $33 million. Of even
      greater significance is the great number of hours devoted by the Committee
      members. Serving on the Audiovisual Committee is similar to taking an advanced
      college course. Selected for their specialized knowledge, members need to learn
      and apply the techniques of the cinema. Far more than just showing a surgical
      procedure, teaching films require the staging of the ideal method while
      explaining its superiority over the method it replaces. Films must be forceful
      enough to overcome the common attitude, "This is the way we've always done it."
      In the course of writing the scripts, which are critiqued by the Committee,
      authors must research the subjects and review the state of the art. They are
      challenged to improve on the past and remain current on changing techniques.
      Service on the Audiovisual Committee prepares members for further involvement in
      AORN activities. Twenty members of the Committee have been elected to the Board
      of Directors, and seven of those have served as AORN Presidents.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7504909
TI  - High-level resistance to (-) enantiomeric 2'-deoxy-3'-thiacytidine in vitro is
      due to one amino acid substitution in the catalytic site of human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - Passage of human immunodeficiency virus type 1 in the presence of increasing 2'
      deoxy-3'-thiacytidine (3TC) concentrations results in high-level (> 100-fold) 3TC
      resistant viruses. All 3TC-resistant viruses possess a substitution at the second
      codon (from a methionine into an isoleucine) at position 184 within the highly
      conserved motif (YMDD) of human immunodeficiency virus type 1 reverse
      transcriptase. 3TC-resistant viruses were cross-resistant to the (-) enantiomer
      of the fluorinated derivative of BCH-189 but remained susceptible to 2',3'
      dideoxyinosine and 2',3'-dideoxycytidine. The susceptibilities of the 3TC
      resistant viruses to the (+) enantiomers of BCH-189 and the fluorinated
      derivative of BCH-189 demonstrate an enantiomeric specificity for viruses
      selected under these conditions. Introduction of an isoleucine substitution at
      codon 184 into a background of two known 3'-azido-3'-deoxythymidine resistance
      mutations (amino acids 41 and 215) restored the susceptibility of this virus to
      3'-azido-3'-deoxythymidine.

PMID- 7504911
TI  - Assessment of feeding problems in neurodevelopmental handicap: a team approach.

PMID- 7504912
TI  - Early pulmonary disease in systemic sclerosis: a comparison between carbon
      monoxide transfer factor and static lung compliance.
AB  - OBJECTIVES: Pulmonary disease is responsible for considerable morbidity and
      mortality in systemic sclerosis (SSc). Static lung compliance (Cst) has been
      observed to be decreased more often in SSc than the vital capacity, indicating
      that it is a sensitive measure of lung restriction. In this study Cst was
      compared with the carbon monoxide transfer factor (TLCO), a widely used measure
      of the function of the alveolar capillary unit, and with lung volumes in 59
      patients with confirmed or suspected SSc. METHODS: Cst was calculated from the
      oesophageal pressure at different lung volumes and the TLCO was measured with the
      single breath method. RESULTS: The TLCO was found to be the earliest sign of
      pulmonary disease and was already decreased at a disease duration of one year or
      less. Surprisingly, no relation was found between the TLCO and smoking habits,
      nor the degree of peripheral vascular disease. The TLCO correlated with the Cst
      and vital capacity. CONCLUSIONS: An early pulmonary lesion can be identified in
      patients with SSc with decreased TLCO at a time when no fibrotic changes are
      manifested.

PMID- 7504913
TI  - Characterisation of the rat oesophagus epithelium antigens defined by the so
      called 'antikeratin antibodies', specific for rheumatoid arthritis.
AB  - OBJECTIVES: An attempt was made to characterise the antigens recognised by serum
      IgG antibodies directed to the stratum corneum of rat oesophagus epithelium, the
      so-called 'antikeratin antibodies', which were shown to be highly specific for
      rheumatoid arthritis (RA) and thus to have an actual diagnostic value. METHODS:
      Immunoblotting was performed with RA serum samples on different extracts of rat
      oesophagus epithelium separated by various monodimensional and two dimensional
      electrophoreses. RESULTS: Three low-salt-soluble antigens sensitive to proteinase
      K and, therefore, of protein nature were identified. Two proteins, with apparent
      molecular masses of 210 and 120-90 kilodaltons, shared isoelectric points ranging
      from 5.8 to 8.5; the third protein exhibited isoelectric points from 4.5 to 7.2
      while its molecular mass ranged from 130 to 60 kilodaltons. Immunoadsorption of
      RA serum samples onto cytokeratins extracted from the stratum corneum of rat
      oesophagus epithelium did not change their immunoreactivity towards the three
      antigenic proteins. Widely used deglycosylation and dephosphorylation methods
      failed to modify either the electrophoretic migration of the proteins or their
      immunoreactivity with RA serum samples. CONCLUSION: The so-called 'antikeratin
      antibodies' do not react with cytokeratins. They specifically recognise three
      late epithelial differentiation proteins which had not been previously described.
      These proteins may be related to (pro)filaggrin.

PMID- 7504914
TI  - Monitoring antithyroid therapy.

PMID- 7504915
TI  - Sequence conservation within neutralization epitope regions of VP7 and VP4
      proteins of human serotype G4 rotavirus isolates.
AB  - Serotype G4 rotavirus isolates causing four separate epidemics of severe
      diarrhoea in young children in Melbourne, Australia (from 1974-1990) were
      investigated for sequence variation in genes encoding the outer capsid proteins,
      VP4 and VP7. Complementary DNA of the gene encoding the major outer capsid
      neutralization antigen, VP7, of eighteen isolates was synthesized and amplified
      by coupled reverse transcription and polymerase chain reaction. Direct sequencing
      methods were used to derive the deduced amino acid sequences of the
      immunodominant A, B, and C neutralization epitope regions of the protein. Limited
      variation was observed among all isolates. A threonine to asparagine change in
      region A, at amino acid 96, was associated with altered binding of serotype G4
      specific neutralizing monoclonal antibodies. The VP8* region of the outer capsid
      protein VP4 (containing the proposed serotype-specific neutralization epitopes)
      was investigated in eight isolates. This region was found to highly conserved
      both within Melbourne isolates and in relation to the standard strains Wa, P, and
      VA70. The characteristic periodicity of occurrence of serotype G4 isolates
      causing severe diarrhoea in Melbourne children is unlikely to be due to changes
      in neutralization epitopes located on the outer capsid proteins, VP7 or VP4.

PMID- 7504916
TI  - Epitopes on the spike protein of a nephropathogenic strain of infectious
      bronchitis virus.
AB  - Infectious bronchitis virus (IBV), the first coronavirus described, was initially
      associated with severe respiratory disease. However, outbreaks have more recently
      also been associated with nephropathogenesis. Topographically interrelated
      antigenic determinants of the nephropathogenic Gray strain of IBV were
      characterized using eleven monoclonal antibodies (MAbs). Four MAbs (IgG 2a kappa)
      defined epitopes that were both conformation-independent and group specific,
      reacting with Gray, Arkansas (Ark), and Massachusetts 41 (Mass 41) strains. Seven
      MAbs (IgG 1 kappa) defined conformation-dependent epitopes that could
      differentiate the Gray from the Ark and Mass strains. The spike protein
      specificity of the MAbs was determined with the conformation-independent MAbs and
      one MAb that reacted only in "non-denaturing" western blot assays. Competitive
      binding studies using these MAbs suggested a high degree of functional dependency
      among the associated epitopes as might be expected with a protein of complex
      secondary and tertiary structure. At least two regions associated with complete
      protection of infected embryos were identified that consisted of both
      conformation-dependent and independent epitopes. However, a "non-neutralizing"
      MAb, which did not protect the embryo from gross lesions, did inhibit virus
      induced lesions and replication in the kidneys. These MAbs should be valuable
      tools in studying IBV pathogenesis.

PMID- 7504917
TI  - Targeted inhibition of immunodeficiency virus replication in lymphocytes through
      retroviral mediated gene transfer.
AB  - To test the feasibility of gene therapy for AIDS patients, an animal model is
      needed to evaluate the efficacy and safety of this approach. Antiviral genes
      (encoding antisense RNA or viral protein) derived from Simian immunodeficiency
      virus (SIV) were efficiently targeted into CD4+ lymphocytes through retroviral
      mediated gene transfer. After challenging with infectious viruses, the transduced
      lymphocytes that received antiviral genes were not only protected from SIV
      infection, but also from infection with HIV, for at least 25 days. Furthermore,
      little or no cytolytic effect (syncytium formation) was observed in the protected
      cells. These data demonstrated that SIV or HIV replication could be effectively
      blocked by antisense sequence(s) or negative dominant factors which were
      introduced into targeted cells through retroviral-mediated gene transfer.

PMID- 7504918
TI  - Evaluation of a monoclonal blocking enzyme-linked immunosorbent assay for the
      detection of Mycoplasma gallisepticum-specific antibodies.
AB  - A monoclonal blocking enzyme-linked immunosorbent assay (blocking-ELISA) was
      developed to detect antibodies to Mycoplasma gallisepticum (MG) in poultry sera
      with the help of a peroxidase-labeled monoclonal antibody (MAb) recognizing an
      epitope of a 56-kilodalton polypeptide (p56) of MG. Immunoglobulins from
      undiluted MG-positive sera prevent the MAb conjugate from attaching to its
      specific binding site on p56, which results in no color development. The opposite
      result--a strong color reaction--was obtained after incubation with MG-negative
      sera (or when no serum was added before the MAb conjugate). Results were
      expressed in percent inhibition or ELISA titers. The blocking-ELISA detected
      84.7% positive chickens in an experimentally infected flock and 72.6% of chickens
      in naturally infected flocks, whereas the hemagglutination-inhibition (HI) test
      was positive only with 68.4% and 48.6% of these serum samples, respectively. All
      HI-positive serum samples reacted positively in blocking-ELISA. Of sera negative
      by the HI test, 51.6% and 46.8% proved to be positive when examined with the
      blocking-ELISA. Overall agreement between the ELISA and HI test was 76.8%.
      Infection with closely related M. synoviae did not induce any false-positive
      reactions in blocking-ELISA. There was a strong positive correlation between HI
      and blocking-ELISA titers (r = 0.83).

PMID- 7504919
TI  - Development and application of a polymerase chain reaction assay for Mycoplasma
      synoviae.
AB  - Mycoplasma synoviae (MS) species-specific primers selected from the 16S rRNA
      sequence were evaluated by polymerase chain reaction (PCR). The MS primers were
      MS-1 (5'-GAAGCAAAATAGTGATATCA-3') and MS-2 (5'-GTCGTCTCCGAAGTTAACAA-3'). Analysis
      of cultures of avian mycoplasmas using the MS PCR indicated 100% specificity and
      sensitivity: 55 individual isolates of MS tested PCR-positive, and 44 isolates of
      eight other species of avian mycoplasmas tested PCR-negative. The MS PCR will
      detect 100 colony-forming units of MS. Analysis of 122 flock data sets indicated
      a sensitivity for the MS PCR test of 82% and a specificity of 100% as determined
      by comparison with culture, serology (serum plate test, hemagglutination
      inhibition, enzyme-linked immunosorbent assay), epizootiology, and history.

PMID- 7504920
TI  - Inhibition of nitric oxide induction from avian macrophage cell lines by
      influenza virus.
AB  - The virulent avian influenza virus A/Ty/Ont/7732/66 (H5N9) (Ty/Ont) causes a
      rapid destruction of lymphoid cells in infected birds. Avian macrophage cell
      lines, HD11 and MQ-NCSU, support productive replication of Ty/Ont and other
      influenza viruses. Therefore, the ability of these cell lines to produce nitric
      oxide (NO), a potentially cytotoxic mediator, in response to infection with
      Ty/Ont was examined. Although treatment with bacterial lipopolysaccharides (LPS)
      resulted in high NO levels, infection of macrophages with Ty/Ont resulted in NO
      levels lower than NO levels in untreated cells. Furthermore, Ty/Ont was able to
      inhibit the positive response to LPS in cultures simultaneously treated with LPS
      and virus. However, inactivated influenza virus did not exhibit this inhibitory
      effect. Different strains of influenza virus varied in their ability to inhibit
      NO production by the macrophages; this may be related to the level of virus
      replication in these cells. These data suggest that the ability of the avian
      macrophage to activate the NO synthesis pathway is seriously impaired by
      infection with virulent influenza viruses such as Ty/Ont.

PMID- 7504921
TI  - Rat cortical synaptosomes have more than one mechanism for Ca2+ entry linked to
      rapid glutamate release: studies using the Phoneutria nigriventer toxin PhTX2 and
      potassium depolarization.
AB  - PhTX2, one of the components of the venom of the South American spider Phoneutria
      nigriventer, inhibits the closure of voltage-sensitive Na+ channels. Incubation
      of cerebral-cortical synaptosomes with PhTX2 causes a rapid increase in the
      intrasynaptosomal free Ca2+ concentration and a dose-dependent release of
      glutamate. This release is made up of a slow component, which appears to be due
      to reversal of Na(+)-dependent glutamate uptake, and more rapid component that is
      dependent on the entry of extrasynaptosomal Ca2+. It has previously been shown
      that membrane depolarization using KCl can cause rapid Ca(2+)-dependent release
      of glutamate from synaptosomes. This requires Ca2+ entry through a specific type
      of Ca2+ channel that is sensitive to Aga-GI, a toxic component of the venom of
      the spider Agelenopsis aperta. We have compared the effects of PhTX2 and KCl on
      elevation of intrasynaptosomal free Ca2+ and glutamate release, and a number of
      differences have emerged. Firstly, PhTX2-mediated Ca2+ influx and glutamate
      release, but not those caused by KCl, are inhibited by tetrodotoxin. Secondly,
      KCl produces a clear additional increase in Ca2+ and glutamate release following
      those elicited by PhTX2. Finally, 500 microM MnCl2 abolishes PhTX2-mediated, but
      not KCl-mediated, glutamate release. These findings suggest that more than one
      mechanism of Ca2+ entry may be coupled to glutamate release from nerve endings.

PMID- 7504922
TI  - Alkaline phosphatase staining of pig and sheep epiblast cells in culture.
AB  - To define better the characteristics of pig and sheep epiblast cells in culture,
      the cells were tested for the presence of alkaline phosphatase (AP), a
      biochemical marker characteristic of mouse embryonic stem cells. Pig and sheep
      epiblast cells were positive for AP staining both at isolation from the
      blastocyst and after primary in vitro culture. The innermost portion of the
      attendant endoderm surrounding the epiblast was also positive for AP staining
      during primary culture. AP staining was lost upon differentiation or senescence
      of the epiblast cells. Also, all differentiated epiblast-derived cell cultures
      were negative for AP staining, with the exception of neuron-like cultures.
      Epiblast-like cells were cultured from day 10 (pig) and day 13 (sheep) embryonic
      discs, and these cells were also AP positive until they differentiated.
      Trophectoderm-endoderm-like cells from embryonic discs were AP negative or weakly
      positive. AP is a convenient marker for undifferentiated pig and sheep epiblast
      cells in culture when used in conjunction with cell morphology analysis.

PMID- 7504923
TI  - Anion channels in the sea urchin sperm plasma membrane.
AB  - Ionic fluxes in sea urchin sperm plasma membrane regulate cell motility and the
      acrosome reaction (AR). Although cationic channels mediate some of the ionic
      movements, little is known about anion channels in these cells. The fusion of
      sperm plasma membranes into lipid bilayers allowed identification of a 150 pS
      anion channel. This anion channel was enriched from detergent-solubilized sperm
      plasma membranes using a wheat germ agglutinin Sepharose column. Vesicles formed
      from this preparation were fused into black lipid membranes (BLM), yielding
      single channel anion-selective activity with the properties of those found in the
      sperm membranes. The following anion selectivity sequence was found: NO3- > CNS-
      > Br- > Cl-. This anion channel has a high open probability at the holding
      potentials tested, it is partially blocked by 4,4'-diisothiocyano-2,2'
      stilbendisulfonic acid (DIDS), and it often displays substates. The sperm AR was
      also inhibited by DIDS.

PMID- 7504924
TI  - Transgenic mice carrying interferon genes.

PMID- 7504925
TI  - Juxtacrine intercellular signaling: another way to do it.
AB  - Intercellular interactions in which one cell sends a signal to another cell,
      inducing a change in function of the second cell, are common in morphogenesis,
      development, inflammation, and repair of the lung and other organs. In juxtacrine
      intercellular signaling, the molecule that induces the functional changes in the
      target cell remains associated with the plasma membrane of the signaling cell,
      rather than acting in the fluid phase. This feature distinguishes juxtacrine
      signaling from endocrine and paracrine stimulation and provides a mechanism for
      strict spatial control of activation of one cell by another. Juxtacrine signaling
      is likely to be common in physiologic events that require tight regulation, and
      disruption of juxtacrine signaling may lead to pathologic outcomes. In this
      minireview, general principles as well as several specific examples of juxtacrine
      signaling are discussed.

PMID- 7504926
TI  - Expression of CFTR and a cAMP-stimulated chloride secretory current in cultured
      human fetal alveolar epithelial cells.
AB  - During development the fetal lung secretes fluid that is osmotically linked to
      chloride (Cl-) transport. One possible pathway for Cl- secretion across the fetal
      pulmonary epithelium is through the cystic fibrosis transmembrane conductance
      regulator (CFTR). CFTR is expressed in epithelia and functions as a Cl- channel
      regulated by cyclic adenosine monophosphate (cAMP)-dependent protein kinase and
      intracellular ATP. Previous studies have shown that CFTR mRNA is expressed
      throughout the human fetal pulmonary epithelium and CFTR protein can be
      immunoprecipitated from human fetal lung homogenates. In cultured fetal lung
      tissue explants, CFTR mRNA was localized to alveolar epithelial cells. To test
      the hypothesis that fetal alveolar epithelial cells express functional CFTR, we
      immunolocalized CFTR in human fetal lung and looked for evidence of Cl- secretion
      in cultured alveolar epithelial cell monolayers. Monoclonal anti-CFTR antibodies
      localized CFTR in cultured lung explants to the epithelial cells, predominantly
      at the apical surface. Bioelectric properties of cultured monolayers of
      midgestation fetal alveolar epithelial cells were measured in modified Ussing
      chambers. In unstimulated monolayers, transepithelial electrical potential
      difference (psi t) = -1.1 +/- 0.1 mV, transepithelial resistance (Rt) = 768 +/-
      58 omega.cm2, and short-circuit current (Isc) = 1.9 +/- 0.2 microA/cm2 (mean +/-
      SE, n = 17). Addition of amiloride to the apical surface significantly decreased
      basal Isc. Apical diphenylamine-2-carboxylate (DPC), a Cl- channel inhibitor,
      caused no significant change in basal Isc. In the presence of apical amiloride,
      isoproterenol significantly increased Isc, a response that was inhibited by
      apical DPC and submucosal bumetanide. The cAMP agonists forskolin and IBMX also
      stimulated Isc.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504927
TI  - Expression and modulation of adhesion molecules on human bronchial epithelial
      cells.
AB  - Epithelial damage in the airways is a feature often observed in patients with
      asthma and is probably caused by the interaction of epithelial cells with
      leukocytes. As adhesion molecules are thought to be important in this
      interaction, we analyzed the expression and modulation of adhesion molecules on
      primary cultured human bronchial epithelial cells and the bronchial epithelial
      cell lines BEAS-2B and NCI-H292. E-selectin, P-selectin, and VCAM-1 were absent
      under basal and stimulated conditions. The adhesion molecules ICAM-1 (CD54), LFA
      3 (CD58), and CD44 (H-CAM) were expressed basally on primary cultured human
      bronchial epithelial cells and the BEAS-2B and NCI-H292 cell lines. CD44 and LFA
      3 expression did not change after stimulation with IFN-gamma or TNF-alpha. In
      contrast, ICAM-1 expression on human bronchial epithelial cells and BEAS-2B cells
      could be increased by incubation with PMA, IFN-gamma, TNF-alpha, and especially
      with the combination of IFN-gamma and TNF-alpha. The maximal ICAM-1 expression on
      both epithelial cell types was obtained with the combination of TNF-alpha and IFN
      gamma after 48 h of incubation. The NCI-H292 cell line was different in that it
      only showed increased ICAM-1 expression after stimulation with PMA and IFN-gamma
      and not by the combination of IFN-gamma and TNF-alpha or with TNF-alpha alone. In
      conclusion, the bronchial epithelial cells tested express several adhesion
      molecules, but only ICAM-1 expression was influenced by inflammatory cytokines.

PMID- 7504928
TI  - Regulation of rat pulmonary endothelial cell interleukin-6 production by
      bleomycin: effects of cellular fatty acid composition.
AB  - Previous studies have shown upregulation of lung cell interleukin-6 (IL-6)
      production in bleomycin-induced pulmonary fibrosis. To further elucidate the
      regulatory mechanisms governing this disease, the effects of bleomycin on the
      production of the pleiotropic cytokine, IL-6, were investigated in lung
      endothelial cells. Rat pulmonary artery endothelial cells were treated with
      bleomycin at doses previously shown to be effective in upregulating cytokine
      production in these cells, and the conditioned media was collected and assayed
      for IL-6 activity. The results show that these endothelial cells constitutively
      produced IL-6 and that bleomycin increased the production in a time- and dose
      dependent manner. Feeding rats diets deficient in n-6 fatty acids is known to
      ameliorate bleomycin-induced lung fibrosis. In order to examine if fatty acids
      could modulate IL-6 production in vitro, cells were lipid depleted and then
      supplemented with 18:1n-9, 18:2n-6, or 18:3n-3 fatty acids, and the effects of
      bleomycin on IL-6 production reexamined. This regimen resulted in significant
      depletion of arachidonate in the 18:1n-9 and 18:3n-3 supplemented cells, which
      was associated with significantly reduced IL-6 production relative to the 18:2n-6
      supplemented cells, both constitutively and when stimulated with bleomycin.
      Preincubation with indomethacin did not significantly inhibit the production of
      IL-6 by all three groups of cells, nor did supplementation with a stable
      prostacyclin analog increase IL-6 production. These results suggest that
      endothelial cell IL-6 production is not directly dependent on prostacyclin or
      other cyclooxygenase metabolites but may require or be upregulated by 18:2n-6
      and/or metabolites derived from it.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504929
TI  - Variable expression of platelet-derived growth factor family proteins in acute
      lung injury.
AB  - During acute lung injury, there is an outpouring of growth factors into the
      alveolar space that drive local repair and fibrosis. During the remodeling that
      follows the instillation of bleomycin via the trachea into the adult rat, at
      least two platelet-derived growth factor (PDGF)-like peptides are released
      sequentially into lung lining fluid. Groups of four to five animals were killed
      at 3, 6, 15, and 26 days after exposure to bleomycin and lungs lavaged with
      isotonic saline. PDGF-like peptides in epithelial lining fluid (ELF) were
      partially purified by cation exchange chromatography and concentrated. Isolated
      peptides were analyzed by immunoblotting to determine their molecular weight and
      immunologic identity. Western blots were probed with polyclonal antibodies to
      PDGF-BB and PDGF-AA. PDGF-like peptides of two distinct size classes (38-40 kD
      and 29 kD) were present in alveolar fluid from all rats with lung injury induced
      by bleomycin. No PDGF-like peptides were found in comparably prepared ELF from
      control animals. The 38-40 kD peptide was detected only with anti-PDGF-BB
      antibody; the 29 kD peptide was detected only with anti-PDGF-AA antibody. The
      presence of these two peptides varied independently with time after exposure to
      bleomycin. The 38-40 kD peptide was at peak levels at 3 to 6 days. In contrast,
      the 29 kD peptide was present at all times following injury but with far less
      variation over time. In parallel with these immunoassays for PDGF-like molecules,
      there was abundant growth-promoting activity for fibroblasts present in
      concentrated ELF during the course of injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7504930
TI  - Plasmalemmal caveolae and GPI-anchored membrane proteins.
AB  - Caveolae are essential endocytic organelles that use glycosyl-phosphatidyl
      inositol (GPI)-anchored membrane proteins to concentrate low molecular weight
      substances before delivery to the cell. Caveolae and GPI-anchored proteins are
      uniquely adapted for this task. Recent advances suggest that this endocytic
      pathway also has an important role in modulating the interaction of a cell with
      its environment. Many vital functions that occur in this organelle remain to be
      discovered.

PMID- 7504931
TI  - Transporters, channels and human disease.
AB  - The past year has seen significant advances in our understanding of the molecular
      biology of ion channels and transporters and their role in human disease. The
      star of the show has to be the cystic fibrosis chloride channel about which an
      enormous amount of information has been accumulated, and the functional effects
      of some of the mutations found in cystic fibrosis patients have been
      characterized.

PMID- 7504932
TI  - Stratification of the channel domain in neurotransmitter receptors.
AB  - Analyses of the ionic pore of ligand-gated ion channels at the amino acid level
      reveal a structural and functional stratification of the M2 channel domain.
      Mutations in the equatorial and outer regions affect channel gating, whereas
      mutations of other amino acid rings alter ionic permeability or selectivity.

PMID- 7504933
TI  - A 90-kDa protein serum marker for the prediction of progression to AIDS in a
      cohort of HIV-1+ homosexual men.
AB  - Levels of a 90-kDa protein (90K), recently reported as a possible marker of HIV-1
      infection, were serially examined in a group of HIV-1-infected (HIV-1+) and
      uninfected (HIV-1-) subjects drawn from the same cohort of homosexual men. The
      first phase of the study included 61 HIV-1+ AIDS-free subjects 4 years (+/- 6
      months) postseroconversion and 75 contemporaneous unifected subjects. Two years
      later, a subset of 35 HIV-1+ AIDS-free subjects and 72 HIV-1- controls was
      examined. Mean 90K levels for HIV-1+ subjects were significantly higher than for
      contemporaneous HIV-1- subjects both 4 and 6 years postseroconversion (p <
      0.0001). A significantly more rapid progression to AIDS was seen in HIV-1+
      subjects with high 90K levels both 4 years (p = 0.01) and 6 years (p = 0.003)
      postseroconversion. Four years postseroconversion, 90K was significantly
      correlated with CD8 cell percent, interferon, neopterin, and beta 2-microglobulin
      (p < 0.05). Two years later, significant correlations were seen between 90K
      levels and CD4 cell percent, CD4 cell number, and beta 2-microglobulin (p <
      0.05). Stepwise-stepdown regression modeling using 90K, CD4 cell percent,
      interferon, and beta 2-microglobulin levels 4 years postseroconversion showed
      that the predictive value of a trivariate model of 90K-interferon-CD4 percent was
      better than any univariate or bivariate model. We conclude that the 90K protein
      may be a useful predictor of progression to AIDS in HIV-1+ patients, particularly
      in combination with the established markers of CD4 cell percent and interferon.

PMID- 7504934
TI  - Characterization of HIV replication complexes early after cell-to-cell infection.
AB  - In this study, we have characterized the HIV DNA-containing replication complexes
      present in cells early after cell-to-cell infection, using sucrose gradient
      sedimentation and immunoprecipitation. Six hours after cell-to-cell infection, a
      cytoplasmic HIV replication complex sedimented as a large structure (320S). This
      replication complex was precipitated by antisera to three virus-coded enzymes
      (reverse transcriptase, integrase, protease), to the matrix protein (p17), and to
      cellular histones but not to the major capsid protein (p24). This replication
      complex was not associated with cell membranes and could not be dissociated into
      smaller discrete subunits, using detergents. Nuclear extracts from the same cell
      to-cell infection contained a smaller (80S) complex that lacked reverse
      transcriptase and matrix protein (p17). Cytoplasmic replication complexes from a
      cell-free virus infection sedimented as 160S structures under identical
      conditions, as previously reported. Our results indicate that, following cell-to
      cell transmission of HIV, all the HIV pol gene products, the matrix protein p17,
      and cellular histones are present in cytoplasmic replication complexes that are
      taking part in or have completed reverse transcription. Transportation of the
      cytoplasmic replication complex to the nucleus is associated with structural
      changes, including a reduction in size and altered protein composition.

PMID- 7504935
TI  - A new type of G-->A hypermutation affecting human immunodeficiency virus.
AB  - A form of G-->A hypermutation preferentially affecting GA dinucleotides of
      genomic RNA has been found to occur in retroviral systems ("type 1"). In a
      detailed longitudinal study of an AIDS patient we have observed a new type of G-
      >A hypermutation, which preferentially affects one or more 5' G residues in runs
      of G's. HIV-1 proviral DNA samples obtained at widely separate times during this
      patient's course contained representatives of this type of G-->A hypermutation,
      designated "type 2." We propose that G-->A hypermutation is caused by a mutated
      form of the HIV-1 reverse transcriptase; and that hypermutated DNA may persist
      for long periods in infected patients, perhaps as proviral DNA in long-lived cell
      lineages. Like type 1 G-->A hypermutation, type 2 G-->A hypermutation may
      contribute to the heterogeneity of replicating pools of HIV by recombination.

PMID- 7504936
TI  - Consequences of human immunodeficiency virus type 1 superinfection of chronically
      infected cells.
AB  - Infection of T cell lines by the type 1 human immunodeficiency virus (HIV-1) is
      associated with downregulation of the CD4 receptor and resistance to further HIV
      1 infection, the phenomenon of viral interference. The ACH2 cell line, a model
      for chronic HIV-1 infection, possesses a single integrated copy of the HIV-1
      strain LAI, is essentially CD4 negative, and can be induced to make virus by a
      variety of stimuli. We utilized the known sequence differences between HIVLAI and
      HIVRF to devise a polymerase chain reaction (PCR) strategy that permits reliable
      and quantitative discrimination between the two strains. We demonstrate that ACH2
      cells can be superinfected by HIVRF at a frequency of 60-300 HIVRF genomes/10(4)
      ACH2 cells and that the frequency of superinfection appears to increase with
      time. Reverse transcription of ACH2 mRNA from days 13, 27, and 38 postinfection
      allowed a similar PCR strategy (RT-PCR) to be used to analyze full-length HIVRF-
      and HIVLAI-specific transcripts. These data suggested that superinfection of ACH2
      with HIVRF results in an increase in expression of both HIVRF and HIVLAI mRNA.
      From day 13 to day 38 postinfection there was an increase in the relative
      expression of HIVRF compared with HIVLAI. By day 38, when only 1.1% of HIV DNA
      sequences were HIVRF derived, roughly 80% of the HIV-specific full-length mRNA
      was HIVRF in origin, with a concomitant decrease in HIVLAI transcription.

PMID- 7504937
TI  - Specificity of antibody-dependent cellular cytotoxicity in sera from human
      immunodeficiency virus type 2-infected individuals.
AB  - ADCC activity in sera from HIV-2-infected individuals was monitored against HIV
      1IIIB, SIVmac, and three different HIV-2 strains. The sera mediated ADCC against
      the HIV-2 strains in high frequencies and reacted equally well with SIVmac,
      whereas no cross-reactivity was seen against HIV-1IIIB. The degree of antigenic
      similarities between the virus strains was also evaluated in order to estimate
      the variability of ADCC target regions. The SIVmac strain and two of the HIV-2
      strains were antigenically more similar to each other whereas another HIV-2
      strain appeared more distantly related with regard to ADCC target regions.
      Although strain-specific ADCC was present in some HIV-2-positive sera, HIV-2 ADCC
      was more broadly reactive and appeared in higher frequencies against these
      specific strains than has been previously shown for HIV-1 ADCC in a group of four
      HIV-1 strains. The difference was, however, not significant. To further delineate
      target regions for ADCC the sera were tested against peptides representing
      different regions of the HIV-2 envelope protein. The V3 region and the C-terminal
      end of gp125 were thus suggested to be involved in ADCC. Target regions for HIV-2
      specific ADCC may only partly overlap with HIV-2-neutralizing regions since the
      two activities were not always present in the same sera. Characterization of
      broadly reacting immune responses like HIV-2-specific ADCC and identification of
      their specific target epitopes is essential for the development of an efficient
      AIDS vaccine.

PMID- 7504938
TI  - Klaus Schwarz medalists of 1992.

PMID- 7504939
TI  - Effect of cadmium on enzymatic digestion and sugar transport in the small
      intestine of rabbit.
AB  - Cadmium compounds are found widely in our environment: for example, in food,
      water, soil, and ambient air. The most important exposure route of animals to
      cadmium in the general environment is via oral exposure. In oral cadmium
      intoxication, the immediate target organ is the gastrointestinal tract. The aim
      of the present work was to determine how cadmium acts on the intestinal
      absorption of sugars and on the sucrase activity through rabbit jejunum, after in
      vitro administration and/or oral administration of CdCl2 in drinking water.
      Results obtained show that cadmium decreases D-galactose accumulation in the
      jejunum tissue. This effect seems to be the results of an action mainly located
      on Na(+)-dependent sugar transport of the mucosal border of the intestinal
      epithelium, because cadmium seems not to modify the sugar diffusion across the
      intestinal epithelium. Cadmium has also been shown to inhibit the (Na(+)-K+)
      ATPase activity of the enterocyte, which might explain the inhibition of the D
      galactose Na(+)-dependent transport. Nevertheless, a direct action of the cadmium
      molecule on the Na(+)-dependent carrier cannot be discarded. Cadmium altered the
      sucrose activity when it was administered in the drinking water for 4 d.

PMID- 7504940
TI  - Plasma molybdenum concentrations in children with and without phenylketonuria.
AB  - Plasma molybdenum concentrations were determined in children, ages two to 12 yr,
      with and without phenylketonuria (PKU). Mean plasma molybdenum concentrations did
      not differ significantly between the children with PKU (1.33 +/- 0.5 microgram/L)
      and without PKU (1.75 +/- 0.8 microgram/L). Plasma molybdenum concentrations in
      both groups of children ranged from < 1 to 3 micrograms/L. When data from all
      children were combined and then separated based on gender, mean plasma molybdenum
      levels did not differ significantly between 9 females (1.56 +/- 0.68 microgram/L)
      and 12 males (1.58 +/- 0.76 microgram/L). Data were also combined and mean (+/-
      SD) plasma molybdenum concentrations calculated for age groups. Two children aged
      1 to < 4 yr had plasma molybdenum concentrations of 1.0 micrograms/L, and six
      children aged 4 to < 7 yr had mean (+/- SD) plasma molybdenum concentrations of
      1.5 +/- 0.8 microgram/L. Eleven children aged 7 to < 11 yr had a mean plasma
      molybdenum concentration of 1.7 +/- 0.7 microgram/L, and two children 11 to < 14
      yr had plasma molybdenum of 1 microgram/L and 2 micrograms/L. Plasma molybdenum
      concentrations did not differ significantly among children in the age groups.

PMID- 7504941
TI  - Simultaneous determination of Zn, Cd, Pb, and Cu in urine of patients with
      blackfoot disease using anodic stripping voltammetry.
AB  - Blackfoot disease (BFD) is an endemic peripheral vascular disorder resulting in
      gangrene of the lower extremities, especially the feet, among residents in a
      limited area on the southwest coast of Taiwan. In the present study, the
      concentrations of zinc, cadmium, lead, and copper in urine of BFD patients with
      matched normal controls are investigated by differential pulse anodic stripping
      voltammetry (DPASV) on a hanging mercury drop electrode (HMDE). The analytical
      results indicate that urinary copper, cadmium, and lead of the BFD patients are
      significantly higher than those of the controls. In addition, the patients showed
      a significantly lower concentration of zinc in the urine than the normal
      controls. The possible connection of these elements with the etiology of the
      disease is discussed.

PMID- 7504942
TI  - Changes of CSF-Cu and -Zn in children with acute lymphoblastic leukemia.
AB  - In 20 Dutch children with acute lymphoblastic leukemia (ALL), Cu and Zn levels in
      cerebrospinal fluid (CSF) were studied during standard treatment (Protocol ALL
      BFM-86/SNWLK-ALL-VII). CSF-Cu in 10 controls was 0.04 +/- 0.02 mumol/L, lower
      compared to values in adults. At the moment of diagnosis, CSF-Cu values were
      higher, 0.06 +/- 0.03 mumol/L, and during maintenance therapy lower, 0.01 +/-
      0.01 mumol/L. Children with central nervous system (CNS) involvement ALL as
      judged by CAT Scan and EEG--in addition to cytology--showed lower CSF-Cu values
      compared to children without. CSF-Zn values were also measured. CSF-Zn was 0.05
      mumol/L and did not vary. Cu/Zn molar ratios were increased at the onset of
      treatment, and decreased during maintenance therapy. The changes in CSF-Cu may
      follow the natural course of the disease or may relate to the success of
      treatment, reflecting a decrease of leukemia activity. Another explanation
      concerns a risk of CNS damage by low CSF-Cu causing neuron dysfunction.
      Conditions necessary for the interpretation of these results into a clinical
      strategy for followup study are outlined.

PMID- 7504943
TI  - Submaximal, aerobic exercise training exacerbates the cardiomyopathy of
      postweanling Cu-depleted rats.
AB  - To determine the dual effect of exercise training and copper depletion on
      myocardial function and ultrastructure, postweanling rats were either trained or
      sedentary while fed copper-adequate or copper-deficient diets for 8 wk. Rats
      developed characteristic myocardial subcellular degeneration and increased
      cardiac mitochondrial volume density when copper depleted, despite lack of overt
      cardiac hypertrophy, hypertension, or anemia. Training combined with copper
      depletion induced mild left ventricular hypertrophy. Basal laminae appeared
      fractionated in areas at capillary-myocyte interface, with focal pericapillary
      and interstitial collagen accumulation, whereas overt fibrosis was absent or
      minimal. Electrocardiograms revealed increased QRS wave and QT duration and
      notching of QRS complex with copper depletion, consistent with intraventricular
      conductance disturbances. The oxidative capacity of soleus muscle increased with
      training in copper-adequate rats, but was reduced with progressive copper
      depletion. These data suggest that copper depletion and training are synergistic
      in effecting focal accumulation of collagen, with deleterious effect on exercise
      capacity.

PMID- 7504944
TI  - Effect of zinc on superoxide-dependent hydroxyl radical production in vitro.
AB  - Trace elements play an important role in oxygen metabolism and therefore in the
      formation of free radicals. Whereas iron and copper are usually the main
      enhancers of free radical formation, other trace elements, such as zinc and
      selenium, protect against the harmful effects of these radicals. To investigate
      the different protective mechanisms of zinc on radical formation, we examined the
      effects of added zinc and copper on superoxide dismutase activity. We also
      studied the effects of copper and iron on xanthine oxidase activity and on the
      Haber-Weiss cycle (iron, superoxide, and hydrogen peroxide), which generates
      hydroxyl radicals in vitro. The hypoxanthine/xanthine oxidase radical generating
      system contained a variety of different physiological ligands for binding the
      iron. This study confirmed the inhibitory effect of copper on xanthine oxidase
      activity. Moreover, it demonstrated that zinc inhibited hydroxyl radical
      formation when this formation was catalyzed by a citrate-iron complex in the
      hypoxanthine/xanthine oxidase reaction. Finally, human blood plasma inhibited
      citrate-iron-dependent hydroxyl radical formation under the same conditions.
      Although trace elements seemed responsible for this antioxidant activity of
      plasma, it is likely that zinc played no role as a plasma antioxidant. Indeed,
      calcium appeared to be responsible for most of this effect under our experimental
      conditions.

PMID- 7504945
TI  - The effects of Zn2+ on guinea pig isolated heart preparations.
AB  - Isolated guinea pig hearts were perfused, by the Langendorff technique, with 30,
      15, 7.5, and 1.5 microM Zn2+ in Chenoweth solution. Contractile force, coronary
      flow, and heart rate were recorded by means of Narco IV Physiograph. Calcium
      inhibitor (Verapamil 1 microM) and anion inhibitor (DIDS: 0.1, 1, and 5 microM)
      were used subsequently in the perfusing solutions in order to distinguish some of
      the possible mechanisms that Zn2+ uses to exert its action on cardiac myocytes.
      Isomolar to zinc concentration of Pb (II) and Co (II) were used to elucidate
      whether zinc effects on heart are specific for this metal. All hearts were used
      to estimate their zinc and calcium content by means of AAS (Atomic Absorption
      Spectrometry). Our findings suggest that the higher the Zn2+ concentration, the
      more toxic effects on heart are expressed by rapid reversible contractile force
      reduction and reversible specific changes of heart rate and flow. Zinc 1.5 microM
      in the perfusing solution benefits heart performance, but not significantly.
      Furthermore, the metal exerts specific effects on guinea pig heart, and it is
      rather possible that these effects on cardiac myocytes are held through cell
      membrane receptors.

PMID- 7504946
TI  - Interaction between zinc and calcium in skeletal muscle in young growing rats.
AB  - The purpose of the present study was to determine whether zinc and calcium could
      interact at the tissue level. In the first part of the study, adult rats were
      injected with ZnCl2 dissolved in a physiological saline solution to determine the
      effects of Zn on Ca levels in various tissues. In the second part of the study,
      weaned rats (at day 22 postnatally) were fed a diet supplemented with Zn until
      day 50 and were then sacrificed. In both instances, blood, brain, heart, liver,
      and skeletal muscle were taken and analyzed. In the Zn-injected group, the brain,
      heart, and liver showed no interaction between Zn and Ca. The skeletal muscle, in
      contrast, showed a decrease in Ca in the homogenate, whereas Zn contents showed a
      significant increase at the sarcoplasmic reticulum (SR). Likewise, in the Zn
      supplemented group, the Zn content of the SR vesicle of the skeletal muscle
      showed an increase, whereas Ca content of the pellet (14,000 g), which contains
      cell debris, nucleus, mitochondria, and SR vesicles of this group, showed a
      decrease. Current findings suggest antagonistic effects between Zn and Ca on this
      tissue. Zn may play a critical role in cellular function through the alteration
      of intracellular distribution of Ca in skeletal muscle.

PMID- 7504947
TI  - Lead effect on the oxidation resistance of erythrocyte membrane in rat triton
      induced hyperlipidemia.
AB  - The anemia observed in severe chronic lead poisoning is in part attributable to
      alterations in the erythrocyte physicochemical properties. Since they are partly
      related to the membrane lipid composition, the aim of the present study was to
      determine the effects of a triton-induced hyperlipidemia on the resistance to
      oxidation of erythrocyte membranes in lead-treated Wistar rats. Our results
      showed that triton administration to lead-treated rats induced an increase in
      erythrocyte choline phospholipid levels together with a significant decrease in
      the erythrocyte membrane lipid resistance to oxidation. These results led us to
      suggest that anemia in lead poisoning is linked to interactions between lead
      present in the membrane and plasma phospholipids. Their increase in rat
      hyperlipidemia induced by triton resulted in a decrease in the membrane
      resistance to oxidation and finally in an erythrocyte fragility leading to their
      destruction.

PMID- 7504948
TI  - Postnatal development of substance-P immunoreactivity in the rat superior
      colliculus.
AB  - Immunocytochemical techniques have been used to examine the distribution of
      substance-P (SP)-labeled neurons in the superior colliculus of rats from birth to
      adulthood. At birth, there are almost no SP-immunopositive neurons in the tectum.
      A small number of SP neurons appear over the next several days. However, the vast
      majority of SP neurons appear between P9 and P10, and by P12 have attained adult
      like numbers and distribution. Neurons are confined to the superficial layers of
      the colliculus, specifically the upper two-thirds of the stratum griseum
      superficiale (SGS). There is no indication of a differential developmental
      sequence along rostrocaudal or mediolateral axes. Neuronal types can be
      distinguished as early as P6 and include horizontal, vertical, and multipolar
      cells. Substance-P-immunoreactive axons and boutons are also present in the
      superior colliculus at birth, and are for the most part confined to the deep
      layers. Boutons are generally of the en-passant type. The density of labeled
      axons and boutons increases progressively, and by P10 there is an almost adult
      like lamination and patchiness. In the adult, labeled axons and boutons are most
      dense in the stratum opticum and stratum griseum intermedium. Bridges of
      dorsoventrally oriented labeled axons span the relatively label-poor stratum
      album intermedium. SP label in the stratum griseum profundum is dense and patchy,
      and there is also dense label in the stratum album profundum bordering the
      periaqueductal grey. The role of substance-P-labeled neurons in the superior
      colliculus is still a matter of speculation. The findings of this study indicate
      that SP neurons may play a role in intrinsic collicular circuitry.

PMID- 7504949
TI  - Using circular permutation analysis to redefine the R17 coat protein binding
      site.
AB  - The bacteriophage R17 coat protein binding site consists of an RNA hairpin with a
      single purine nucleotide bulge in the helical stem. Circular permutation analysis
      (CPA) was used to examine binding effects caused by a single break in the
      phosphodiester backbone. This method revealed that breakage of all but one
      phosphodiester bond within a well-defined binding site substantially reduced the
      binding affinity. This is probably due to destabilization of the hairpin
      structure upon breaking the ribose phosphates at these positions. One circularly
      permuted isomer with the 5' and 3' ends at the bulged nucleotide bound with wild
      type affinity. However, extending the 5' end of this CP isomer greatly reduces
      binding, making it unlikely that this circularly permuted binding site will be
      active when embedded in a larger RNA. CPA also locates the 5' and 3' boundaries
      of protein binding sites on the RNA. The 5' boundary of the R17 coat protein site
      as defined by CPA was two nucleotides shorter (nucleotides -15 to +2) than the
      previously determined site (-17 to +2). The smaller binding site was verified by
      terminal truncation experiments. A minimal-binding fragment (-14 to +2) was
      synthesized and was found to bind tightly to the coat protein. The site size
      determined by 3-ethyl-1-nitrosourea-modification interference was larger at the
      5' end (-16 to +1), probably due, however, to steric effects of ethylation of
      phosphate oxygens. Thus, the apparent site size of a protein binding site is
      dependent upon the method used.

PMID- 7504950
TI  - Inhibition of the activity of protein tyrosine phosphate 1C by its SH2 domains.
AB  - Full-length protein tyrosine phosphatase 1C (PTP1C), the catalytic domain of
      PTP1C (delta PTP1C), and the N-terminal SH2 domain truncated PTP1C (delta NPTP1C)
      were overexpressed in Escherichia coli and purified to near homogeneity. Various
      phosphorylated states of the synthetic phosphotyrosyl peptide TRDIYETDYYRK (IRP),
      corresponding to the major insulin receptor autophosphorylation sites, were used
      as substrates for the PTPs. There was no indication for selective
      dephosphorylation of any of the three phosphotyrosyl residues from the
      triphosphotyrosyl IRP. Kinetic studies were carried out using all seven different
      phosphotyrosyl IRPs. Saturation kinetics were observed for PTP1C using the
      triphosphotyrosyl IRP only. In contrast, for delta PTP1C, saturation was achieved
      for all seven phosphotyrosyl IRPs. The best substrate for delta PTP1C was the
      triphosphotyrosyl IRP possessing a Km of approximately 1.6 microM, about 3-4-fold
      lower than either the mono- or diphosphotyrosyl IRPs. However, in contrast to
      delta PTP1C, PTP1C had a 22-fold lower affinity for triphosphotyrosyl IRP.
      Furthermore, deletion of a single N-terminal SH2 domain increased the affinity of
      the enzyme for the triphosphotyrosyl IRP to a value similar to that obtained with
      delta PTP1C. The pH optima for all three enzyme constructs were very similar and
      could not account for the observed change in substrate affinity between the three
      enzymes. These results suggest that the SH2 domain of PTP1C exerts an inhibitory
      effect on its PTP activity.

PMID- 7504951
TI  - Purification and characterization of the cytoplasmic domain of human receptor
      like protein tyrosine phosphatase RPTP mu.
AB  - RPTP mu is a recently described receptor-like protein tyrosine phosphatase (PTP),
      the ectodomain of which mediates homophilic cell-cell adhesion. The cytoplasmic
      part contains two homologous PTP-like domains and a juxtamembrane region that is
      about twice as large as in other receptor-like PTPs. The entire 80-kDa
      cytoplasmic part of human RPTP mu was expressed in insect Sf9 cells and its
      enzymatic activity was characterized after purification to electrophoretic
      homogeneity. In addition, the effects of deletion and point mutations were
      analyzed following expression in Escherichia coli cells. The purified cytoplasmic
      part of RPTP mu displays high activity toward tyrosine-phosphorylated, modified
      lysozyme (Vmax 4500 nmol min-1 mg-1) and myelin basic protein (Vmax 8500 nmol min
      1 mg-1) but negligible activity toward tyrosine-phosphorylated angiotensin or the
      nonapeptide, EDNDpYINASL, that serves as a good substrate for protein tyrosine
      phosphatase PTP1B. This suggests that RPTP mu and PTP1B have distinct substrate
      specificities. Catalytic activity is independent of Ca2+ (up to 1 mM) but is
      strongly inhibited by Zn2+, Mn2+, vanadate, phenylarsenic oxide, and heparin. The
      first of the two catalytic domains is 5-10 times less active than the expressed
      catalytic region containing both domains. Mutation of Cys 1095 to Ser in the
      first catalytic domain abolishes enzymatic activity when analyzed following
      expression in either E. coli or mammalian COS cells. Deletion of the first 53
      amino acids from the juxtamembrane region reduces catalytic activity about 2
      fold.

PMID- 7504952
TI  - New evidence for a membrane-bound pathway in hormone receptor binding.
AB  - The fully active cholecystokinin analog (Thr,Nle)-CCK-9 was lipo-derivatized by N
      terminal grafting of a dimyristoylglycerol moiety to induce tight interdigitation
      with cell membrane bilayers. While the parent CCK peptide was shown to interact
      only transiently with small unilamellar phospholipid vesicles, the lipo-CCK
      peptide, although self-aggregating into vesicles, inserts rapidly and
      quantitatively into phospholipid bilayers. Fluorescence and, even more so, NMR
      data are supportive for a chain reversal of the CCK moiety of the lipo derivative
      with embedment of the C-terminus into hydrophobic compartments of the bilayer. MD
      simulations allowed for a proposal of the folded form of CCK in bilayers with a
      helical array parallel to the interface and an amphipathic display of the side
      chains. In this model, the phenylalanine aromatic ring is heading the peptide
      molecule and may thus play a decisive role in the lateral penetration of the
      receptor at the water/lipid interface. In fact, despite the membrane-bound state,
      its binding affinity for rat pancreatic acini is comparable to that of the CCK
      peptide when tested after a 3-h equilibration period but 5-6-fold lower at 45
      min, suggesting that the association rate is significantly lower than that of the
      unmodified CCK peptide. This can rationally be attributed to the tight
      interdigitation of the double-tailed lipo moiety with the membrane bilayer.
      Moreover, an escape of the lipopeptide into the extracellular aqueous phase is
      energetically highly unfavored; therefore, the receptor can only be reached by a
      membrane-bound two-dimensional migration. The observed difference in
      amplification between binding and amylase secretion may result from inadequate
      occupation of low-affinity CCK receptors, which leads then to poor couplings to G
      proteins. Nevertheless the data confirm that lateral penetration of receptor
      structures is possible, and thus, preadsorption of peptide (neuro)hormones at the
      cell membrane bilayer may indeed represent the first step in the receptor
      recognition process.

PMID- 7504953
TI  - Tertiary interactions with the internal guide sequence mediate docking of the P1
      helix into the catalytic core of the Tetrahymena ribozyme.
AB  - The L-21 ScaI ribozyme catalyzes sequence-specific cleavage of an oligonucleotide
      substrate. Cleavage is preceded by base pairing of the substrate to the internal
      guide sequence (IGS) at the 5' end of the ribozyme to form a short RNA duplex
      (P1). Tertiary interactions between P1 and the catalytic core dock P1 into the
      active site of the ribozyme. These include interactions between the catalytic
      core and 2'-hydroxyls of the substrate at nucleotide positions -3u and perhaps 
      2c. In this study, 2'-hydroxyls of the IGS strand that contribute to P1
      recognition by the ribozyme are identified. IGS 2'-hydroxyls (nucleotide
      positions 22-27) were individually modified to either 2'-deoxy or 2'
      methoxynucleotides within full-length semisynthetic L-21 ScaI ribozymes generated
      using T4 DNA ligase. Thermodynamic and kinetic characterization of the resulting
      IGS variant ribozymes justify the following conclusions: (i) 2'-Hydroxyls at
      nucleotide positions G22 and G25 play a critical energetic role in docking P1
      into the catalytic core, contributing 2.6 and 2.1 kcal.mol-1, respectively. (ii)
      The loss of binding energy is manifest primarily as an increase in the rate of
      dissociation. Because turnover for the wild-type ribozyme is limited by product
      dissociation, G22 and G25 deoxy variants display up to a 20-fold increase in the
      multiple-turnover rate at saturating substrate. (iii) IGS tertiary interactions
      are energetically coupled with the tertiary interactions made to the substrate,
      consistent with P1 becoming undocked from its binding site in J8/7 upon
      substitution of either the G22 or G25 2'-hydroxyl. (iv) The G22 deoxy variant
      loses energetic coupling between guanosine and substrate binding, suggesting that
      in this variant the P1 helix is also undocked from its binding site in J4/5, the
      proposed site of guanosine and substrate interaction. Therefore, in combinations
      with previous studies four P1 2'-hydroxyls are implicated as important for
      docking. The contributions of the 2'-hydroxyl tertiary interactions are not
      equivalent and follow the hierarchical order G22 > G25 >> -3u > -2c. Because the
      G22 2'-hydroxyl appears to mediate P1 docking into both J8/7 and J4/5, it may
      serve as the molecular linchpin for the recognition of P1 by the catalytic core.

PMID- 7504954
TI  - Analysis of nucleosome assembly and histone exchange using antibodies specific
      for acetylated H4.
AB  - Using antibodies that specifically recognize the acetylated forms of histone H4,
      we show that it is possible to immunoprecipitate newly assembled (acetylated)
      nucleosomes. Newly replicated HeLa cell chromatin was labeled for 5-30 min with
      [3H]thymidine in the presence of sodium butyrate (thus inhibiting the
      deacetylation of newly deposited H4); bulk chromatin DNA was labeled for 24 h
      with [14C]thymidine. When soluble nucleosomes were incubated with immobilized
      antibodies, a comparison of the bound and unbound fractions showed up to a 65
      fold enrichment for new chromatin DNA in the immunoprecipitate (bound), relative
      to the supernatant (unbound). No enrichment for new DNA was observed when
      preimmune control serum was used in a similar fashion. The enrichment for new DNA
      in the immunopellet was paralleled by a similar enrichment for all four newly
      synthesized histones. Acetylation was required for antibody recognition: When
      chromatin was replicated in the absence of butyrate (permitting histone
      deacetylation and chromatin maturation), equally low levels of new and old
      chromatin were immunoprecipitated, and no enrichment for new DNA was observed.
      Competition experiments confirmed these results. Analyses of histone deposition
      during the inhibition of DNA replication established that acetylated chromatin is
      the preferential target for H2A/H2B exchange. These experiments provide evidence
      for the highly selective assembly of newly synthesized H3, H2A, and H2B with
      acetylated H4, and for the involvement of histone acetylation in dynamic
      chromatin remodeling. In addition, immunoprecipitations of radiolabeled cytosolic
      extracts identified a possible somatic chromatin preassembly complex, containing
      newly synthesized H3 and new (acetylated) H4.

PMID- 7504955
TI  - Position and orientation-selective silencer in protein-coding sequences of the
      rat osteocalcin gene.
AB  - Osteocalcin (OC) is a bone-specific protein which is expressed
      postproliferatively by osteoblasts during late stages of differentiation. We have
      found that a silencer element is present within the rat OC gene (between nt +39
      and +104), overlapping the OC signal prepropeptide-coding sequence. The presence
      of this sequence in OC promoter-CAT reporter constructs suppresses promoter
      activity in transiently transfected proliferating osteoblasts, which do not
      express OC, by up to 50-fold. This is the first demonstration of contribution
      from protein-coding sequences to silencing of animal genes. The element appears
      to be bipartite; silencer activity requires both the protein-coding sequence +39
      to +63 and the +93 to +104 exon 1/intron 1 border region. Both of these domains
      contain sequences highly similar to silencer motifs in several other genes,
      including chicken lysozyme as well as rat collagen type II, insulin, and growth
      hormone. OC silencer activity is fully retained when the element is placed
      outside the RNA-coding region, 3' but not 5' of the OC-CAT fusion gene.
      Repression activity is orientation independent in the native position but
      requires the native orientation when located in 3' extragenic positions. The
      silencer does not inhibit the activity of the heterologous SV40 early promoter.
      These results suggest interaction between the transcribed silencer and specific
      OC promoter element(s) residing farther upstream. The OC transcribed silencer may
      contribute to developmental control of OC expression.

PMID- 7504956
TI  - Efficient generation of human anti-cytomegalovirus IgG monoclonal antibodies from
      preselected antigen-specific B cells.
AB  - Human anti-cytomegalovirus (CMV) specific B cells were enriched to a purity of up
      to 38% on CMV-coated dishes and subsequently clonally expanded in the presence of
      human T cell supernatant and irradiated murine thymoma helper cells. The expanded
      cells were immortalized by a mini-electrofusion with K6H6B5 myeloma cells. Twenty
      two anti-CMV positive B cell clones could be obtained from as little as 1.5 ml
      donor blood. The majority of these clones produced anti-CMV antibodies of the IgG
      class. Ten anti-CMV positive B cell clones were submitted to separate mini
      electrofusions yielding stable, human anti-CMV IgG-producing hybridomas in six
      out of ten fusions. These antibodies recognized different proteins of the CMV
      virus, as deduced from the immunofluorescence staining pattern on infected human
      fibroblasts.

PMID- 7504957
TI  - The role of beta 1 integrins in tumors.
AB  - Members of the beta 1 subfamily of integrins contribute to cell adhesion,
      cytoskeletal organization and signal transduction processes. In some transformed
      cell lines and tumors, a correlation has been established between the level of
      expression of the alpha 5/beta 1 fibronectin receptor and neoplastic behavior. In
      other instances, normal and neoplastic tissue differ in beta 1 integrin
      expression or sub-cellular distribution. The level of expression of beta 1
      integrins in tumor cells may affect tumor growth properties in several ways,
      including: (a) effects on anchorage dependence of growth; (b) direct signaling
      processes; (c) organization of the extracellular matrix and presentation of
      matrix bound growth factors; (d) effects on the functions of host defense cells.
      Thus the interplay between integrin expression and tumor behavior is complex and
      might be viewed as a series of interactive feedback loops rather than in terms of
      a straightforward cause and effect relationship.

PMID- 7504959
TI  - Molecular mechanisms of invasion by Entamoeba histolytica.
AB  - Amebiasis is the third leading cause of death due to parasitic disease. Adherence
      to and contact-dependent killing of host cells requires the galactose-inhibitable
      lectin, a heterodimeric glycoprotein composed of heavy and light subunits. The
      cysteine-rich extracellular domain of the heavy subunit has identity with beta 1
      integrins, complement receptor CD59, and complement components C8 and C9; the
      light subunit sequence is unlike any other sequenced protein. Monoclonal
      antibodies to the cysteine-rich domain identify pathogenic-specific domains, have
      adherence-inhibitory and -enhancing properties, block contact-dependent
      cytotoxicity, and abrogate complement C5b-9 resistance. The purified lectin has
      galactose-binding activity and confers C5b-9 resistance to susceptible amebae.
      The accumulated evidence points to the same cell surface galactose-inhibitable
      lectin as a mediator of two activities required for invasion: adherence and
      complement resistance.

PMID- 7504958
TI  - Tenascin and other adhesion-modulating proteins in cancer.
AB  - A loss in cell-cell adhesion and an increase in cell motility are clearly
      prerequisites for the development of invasive tumors and metastasis. Since
      disseminating tumor cells have to interact with and migrate through extracellular
      matrices it is of interest to compare the composition of extracellular matrix
      proteins in normal and tumor tissues, in order to determine whether the
      extracellular matrix could be critically involved in affecting tumor cell
      adhesion and migration. The question will be addressed whether tumor
      extracellular matrix contains increased amounts of potentially antiadhesive
      extracellular matrix components and whether cells behave differently depending on
      the extracellular matrix they encounter. The results reviewed support the
      hypothesis that changes in the extracellular matrix and the cellular receptors
      are indeed important in the process of tumorigenesis.

PMID- 7504960
TI  - Epitope mapping of the 273-284 region of HSV glycoprotein D by synthetic branched
      polypeptide carrier conjugates.
AB  - To investigate the antigenicity of a predicted epitope region of herpes simplex
      virus gD, peptides comprising the 273-284 sequence have been synthesized and
      conjugated to a branched polypeptide with polylysine backbone (poly[L-Lys-(DL
      Alam)], AK). In order to analyze the effect of the carrier on the solution
      conformation of the potential peptide-epitopes, three peptides (273-284, 273-281
      and 276-284) and their polypeptide conjugates were studied by CD spectroscopy in
      PBS or in TFE. In immunized BALB/c and CBA mice, the level of peptide-, conjugate
      and carrier-specific antibody responses were measured. Conjugates with synthetic
      polypeptide carrier AK induced epitope-specific IgG responses, accompanied by the
      appearance of a low level of carrier-specific antibodies. The cross-reactivity
      pattern of induced antibodies revealed the presence of at least two functionally
      distinct, overlapping epitopes, the availability of which was influenced by
      flanking residues at the N-terminus. Preimmunization of BALB/c or CBA mice with
      the [276-284]-AK conjugate resulted in the production of HSV-specific antibodies
      and in prolonged survival of animals infected with a lethal dose of herpes
      simplex virus. The degree of protection was comparable to that of [1-23]-AK
      conjugate (30).

PMID- 7504961
TI  - Depth-dependent effects of DDT and lindane on the fluidity of native membranes
      and extracted lipids. Implications for mechanisms of toxicity.

PMID- 7504962
TI  - Effect of sub-chronic lindane exposure on humoral and cell-mediated immune
      responses in albino rats.

PMID- 7504964
TI  - Road traffic and respiratory health of children.

PMID- 7504963
TI  - [Clinical and experimental observations of buzhong yiqi decoction in the
      treatment of chronic hepatitis B].
AB  - A clinical observation of Buzhong Yiqi decoction (BZYQD) and Western medicine was
      used on a matched control in treating chronic hepatitis B. The result showed that
      BZYQD was significantly better than the Western medicine in improving clinical
      symptoms and signs, the liver function and serological test of hepatitis B
      antigen-antibody system (HBAg-Ab system), P < 0.05. In order to explore the
      therapeutical mechanism of BZYQD, the study of the effects of which on synthesis
      of hepatic DNA, RNA and protein in mice were performed too. The results showed
      that BZYQD had marked promotive effects on the synthesis of hepatic DNA, RNA and
      protein. It was considered that the mechanism of anti-hepatitis effects might
      related to the enhancing protein synthesis in liver, promoting the repairs of the
      damaged liver tissue and improving the defense function of organism as a whole.

PMID- 7504965
TI  - The role and fate of the CD4 molecule in lymphocytes and monocytes infected by
      HIV-1.
AB  - Infection by HIV-1 of monocyte cell lines, in contrast to T lymphocytes, did not
      lead to decreased steady-state levels of CD4 mRNA. Similar results were also
      obtained using clonal derivatives of infected U-937 cells that produced either
      competent, highly replicative progeny viruses or defective non-infectious
      particles. In each case, the infected U-937 cells or clonal derivatives were
      found to be significantly deficient with regard to surface representation of CD4
      protein, in spite of the presence of high levels of CD4 mRNA. However, both HIV-1
      infected U-937 cells, as well as clonal derivatives which produced high levels of
      viral env mRNA and non-infectious viral structures that lacked envelope
      glycoproteins, contained diminished levels of OKT4-immunoprecipitable CD4
      protein, in comparison with uninfected U-937 cells. Thus, expression of viral env
      mRNA but neither the efficient synthesis or packaging of viral glycoproteins or
      viral assembly is required for disappearance of cell surface CD4 to occur.
      Furthermore, viral gp160 co-precipitated with CD4 in both the parental and cloned
      cell lines. We have also shown that the generation of intracellular complexes of
      gp160 and CD4 is directly responsible for the disappearance of cell surface CD4
      in HIV-1-infected U-937 cells. In this system, expression of gp160 was both
      necessary and sufficient to result in CD4 receptor down-modulation. Finally, in
      vitro co-translation studies revealed that the presence or synthesis of viral
      gp160 led to a failure to efficiently generate CD4 protein.

PMID- 7504966
TI  - HIV resistance to anti-viral drugs.
AB  - The use of zidovudine (ZDV) and other forms of nucleoside therapy, including
      dideoxyinosine (ddI), to treat HIV-infected individuals has led to both longer
      survival and improved quality of life. However, ZDV-resistant variants of HIV-1
      can be isolated from patients undergoing prolonged therapy with this drug. HIV
      drug resistance against ZDV, ddI and other nucleosides is attributable to a
      series of point mutations within the pol gene of HIV-1 that encodes the viral
      enzyme, reverse transcriptase (RT). This is not surprising, since the virus is
      known to replicate at high rates in infected individuals; moreover the RT which
      mediates transcription of proviral DNA from viral genomic RNA is known to be
      highly error-prone. Thus, mutants of HIV-1, which possess a drug resistance
      phenotype and genotype, may be expected to emerge under the selective pressure of
      long-term anti-viral chemotherapy. HIV drug resistance occurs most commonly in
      individuals with low CD4 counts, who have progressed to more serious forms of
      disease. Moreover, viruses obtained from patients with AIDS generally display
      higher levels of resistance, relative to pre-treatment isolates, than do viruses
      from patients with more limited illness. Although observations of drug resistance
      can be correlated with disease progression and a weakened immune system, it is
      still unclear whether a cause and effect relationship exists. Current clinical
      research is designed to answer this question while testing the notion that
      combinations of nucleosides and immuno-stimulatory drugs may provide important
      clinical benefits.

PMID- 7504967
TI  - Role of the amygdala, hippocampus and entorhinal cortex in memory consolidation
      and expression.
AB  - 1. Experiments using localized microinfusions of specific agonists and
      antagonists of neurotransmitter receptors have shown that the amygdala,
      hippocampus, medial septum and entorhinal cortex are involved in memory
      consolidation, storage and expression. The data are consistent with observations
      derived from lesion studies suggesting a role for these structures in memory
      processes, but permit many additional conclusions concerning the mechanisms
      involved and their timing. 2. Memories are initially processed by glutamatergic N
      methyl-D-aspartate (NMDA) receptors in amygdala, hippocampus and medial septum,
      which are sensitive to amino-phosphono valerate (AP5). Memory of inhibitory
      avoidance is processed by the three structures; memory of habituation to a novel
      environment is processed only by the hippocampus. At the time of consolidation,
      immediately after training, gamma-aminobutyrate type A (GABA-A) receptors,
      modulated by endogenous benzodiazepines, play an inhibitory role, and cholinergic
      muscarinic and beta-noradrenergic transmission play a modulatory role. 3. From 90
      to 180 min after training, memories are blocked by cyano-nitro-quinoxalinedione
      (CNQX) given into the amygdala, septum and hippocampus. CNQX blocks non-NMDA
      glutamatergic receptors. Also between 90 and 180 min after training, memory of
      the habituation and inhibitory avoidance tasks is blocked by the infusion of AP5
      or of the GABA-A agonist, muscimol, into the entorhinal cortex. This late post
      training intervention of the entorhinal cortex is essential for the integration
      of successively acquired memories, and occurs in response to the simultaneous
      activation of CNQX-sensitive synapses in amygdala and hippocampus. 4. The
      expression of memory is blocked by the infusion of CNQX, at the time of testing,
      into the amygdala and hippocampus (inhibitory avoidance), into the hippocampus
      but not the amygdala (habituation), or into the entorhinal cortex (for the two
      tasks). Since consolidation is blocked by AP5 infused into these structures (see
      above), the data agree with the hypothesis that memories are mediated by (or
      actually consist of) long-term potentiation (LTP) in these areas of the brain.
      LTP induction is blocked by AP5 and LTP expression is blocked by CNQX. It is
      possible that, at the time of memory expression, the entorhinal cortex is an
      output of the amygdala and hippocampus.

PMID- 7504968
TI  - Expression of the VP3-VP1 sequence of foot-and-mouth disease virus in Escherichia
      coli.
AB  - 1. cDNA recombinants containing the VP3 and VP1 sequences of foot-and-mouth
      disease virus were isolated and the VP3-VP1 sequence was reconstructed. 2. The
      reconstructed VP3-VP1 sequence was subcloned into expression vector pEX31b and a
      fusion protein of about 62,000 Da was expressed. 3. When injected into mice, the
      fusion protein was able to elicit the production of antibodies that recognized
      viral VP1 and VP3. 4. Antibodies present in sera from mice immunized with VP3-VP1
      protein did not neutralize the foot-and-mouth disease virus in vitro.

PMID- 7504969
TI  - Screening of 62 mutations in a cohort of cystic fibrosis patients from north
      eastern Italy: their incidence and clinical features of defined genotypes.
AB  - The frequency of 62 different CFTR mutations in 225 chromosomes from a CF birth
      cohort, which includes all the affected subjects born in northeast Italy during a
      10-year period of time, was investigated. New mutations were also searched by the
      analysis of 15 different exons. The total proportion of CF chromosomes with
      detectable mutations is 73.78%. Therefore although a considerable improvement in
      CF mutation detection in our population has been achieved, the search for other
      common and uncommon mutations should be continued. Moreover a carrier screening
      program should be postponed until reaching a cumulative proportion of known CF
      alleles of at least 90%. The correlations between the genotypes which have been
      identified and the main clinical features added some new information to the
      classification of CF mutations as pancreatically severe or mild ones.

PMID- 7504970
TI  - Molecular characterization of a frameshift mutation in exon 19 of the CFTR gene.

PMID- 7504971
TI  - Monitoring the incidence of tuberculosis in England and Wales.

PMID- 7504972
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7504973
TI  - British Paediatric Surveillance Unit.

PMID- 7504974
TI  - Prevalence of anti-hepatitis C virus antibodies among teenagers in the Venetian
      area: a seroepidemiological study.
AB  - OBJECTIVES: To establish the prevalence of circulating anti-hepatitis C virus
      antibodies and investigate hepatitis B virus serology, in adolescents in Chioggia
      (Venitia), Italy. METHODS: We conducted a population based survey of 1,015
      fourteen-year-old school children, 529 boys and 486 girls. All were testing for
      hepatitis C antibodies with second generation enzyme-linked immunosorbent assay
      (ELISA). Four immunoblotting tests were used to confirm positive ELISA tests.
      Hepatitis B (HB) markers, HBs, anti-HBs and anti-HBc, were tested with commercial
      ELISA kits. RESULTS AND COMMENTS: Fourteen children were positive for anti-HCV
      antibodies, after confirmation with four immunoblotting tests. No significant
      difference was seen between the prevalence rate in males (0.41%) and females
      (0.38%) or between urban (0.43%) or rural (0.31%) dwellers. A significant
      variation of rate (12.5% to 0.2%) was seen in subjects with or without previous
      HBV infection. A positive relationship between age and prevalence of antibodies
      to HCV was noted, suggesting a late acquisition of infection in our district.
      Nine subjects had had a history of apparent parenteral exposure and only 1 was
      anti-HCV positive. Among HCV positive subjects only 25% had a history positive
      for parenteral exposure.

PMID- 7504975
TI  - Is there a place for G-CSF in viral hepatitis-induced agranulocytosis?

PMID- 7504976
TI  - Toxic hepatitis induced by antithyroid drugs: four cases including one with cross
      reactivity between carbimazole and benzylthiouracil.
AB  - OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse
      effects encountered with antithyroid drugs. METHODS: Retrospective review of
      medical records of 236 patients with hyperthyroidism admitted in our department
      (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were
      identified with toxic hepatitis which could reasonably be attributed to the use
      of antithyroid agent. Two patients had a cholestatic hepatitis induced by
      carbimazole (Neomercazole). Two others had a mixed (cholestatic and cytolytic)
      hepatitis following carbimazole. One of the latter two patients further
      experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basdene)
      had replaced carbimazole. Biological features of hepatitis disappeared in all
      cases after cessation of the incriminated drug, while biliary, viral and
      immunological searches were negative. Only 2 patients of our retrospective study
      experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a
      potential adverse effect of antithyroid drugs which warrants, as for
      haematological disturbances, a pre-therapeutic determination and a careful follow
      up of relevant biological markers. Moreover, hepatotoxicity may not be restricted
      to one class of antithyroid agents.

PMID- 7504977
TI  - [The use of antifibrinolytics in heart surgery. 3 prospective studies].
AB  - In order to assess the validity of antifibrinolytic treatments in cardiac
      surgery, three successive controlled randomized double-blind studies were carried
      out in patients undergoing a first (n = 60) or repeat surgical procedure because
      of a valvular or coronary disease. The first study aimed at stating the value of
      low doses of aprotinin compared with "classical" ones and a placebo. The second
      study was planned to compare tranexamic acid with low-dosed aprotinin and a
      placebo. The last study applied to reiterated procedures and compared tranexamic
      acid with classical and reduced aprotinin dosages, without a placebo group.
      Effects were estimated on postoperative bleeding, blood transfusions, platelets
      function and possible complications such as thrombosis or seric creatinine
      elevation. A reduced bleeding was observed in the non-placebo groups of studies I
      and II. The 3d study did not show any significant differences in this respect
      between the three methods. Tranexamic acid was found as effective as aprotinin on
      platelets function. No significant changes of seric creatinine was observed from
      preoperative to 4th postoperative day. A valvular non-obstructive thrombosis
      occurred on the second postoperative week in the tranexamic acid group.

PMID- 7504978
TI  - Prognostic factors in metastatic nonseminomatous germ cell tumours.
AB  - OBJECTIVE: To determine predictors of prognostic significance for patients with
      nonseminomatous testicular cancer (NSTC) who have advanced disease at the time of
      presentation. DESIGN: A chart review with a mean patient follow-up of 5.5 years
      (range from 0.75 to 13 years). SETTING: University hospitals in Halifax.
      PATIENTS: All patients with NSTC, stages II-B, II-C and III. Patients were
      excluded if the follow-up status at the time the study closed could not be
      determined. Thirty-three patients were included in the study. Current patient
      status was determined from the clinical charts and personal communication with
      the patients or their physicians. INTERVENTIONS: All patients received
      cisplatinum-based chemotherapy. The extent of the disease was assessed by chest
      radiography or lung tomography, bone scanning, abdominal computed tomography or
      lymphangiography. MAIN OUTCOME MEASURES: Correlation between levels of beta-human
      chorionic gonadotropin (BHCG) and alpha-fetoprotein (AFP), comparison of duration
      of symptoms before initial treatment, response to treatment and survival, and
      relationship between stage, tumour volume and survival. RESULTS: The 3-year
      overall survival rate was 76%. Seven of 18 patients with symptoms for more than
      16 weeks died of disease (p < 0.01). Overall complete response was seen in 27 of
      33 patients. All initial nonresponders died. A survival rate of 93% was seen
      among initial complete responders (p < 0.01). All seven patients with persistent
      elevation of BHCG levels (p < 0.001) and the two patients with persistent
      elevation of AFP levels (p < 0.01) after the second course of chemotherapy died.
      CONCLUSIONS: A symptomatic interval of more than 16 weeks, poor response to
      initial treatment, bulky retroperitoneal disease, larger volume lung disease and
      persistently elevated levels of BHCG and AFP were all indicators of poor
      prognosis.

PMID- 7504979
TI  - Antibodies to murine CD40 stimulate normal B lymphocytes but inhibit
      proliferation of B lymphoma cells.
AB  - A rat anti-mouse CD40 antiserum has been prepared by hyperimmunisation of Lewis
      rats with a highly purified preparation of the recombinant extracellular domain
      of murine CD40. This antiserum specifically binds CD40-expressing L cell
      transfectants, but not untransfected L cells, and induces vigorous proliferation
      of highly purified small dense B cells obtained from the spleens of unstimulated
      mice. Anti-CD40-induced B cell proliferation can be augmented by the addition of
      IL-4 and is inhibited by purified recombinant soluble mouse CD40. Interestingly
      the same anti-CD40 antiserum specifically inhibits the in vitro growth of A.20
      murine B lymphoma cells. The specificity of this inhibition can be demonstrated
      by reversing the effect with purified recombinant soluble mouse CD40. These data
      implicate CD40 as a possible target for therapeutic intervention in the treatment
      of B lymphomas.

PMID- 7504981
TI  - A novel monoclonal human IgM autoantibody which binds recombinant human and mouse
      tumor necrosis factor-alpha.
AB  - Several monoclonal human IgM antibodies to recombinant human tumor necrosis
      factor-alpha (rhTNF alpha) have been generated and partially characterized. The
      F78-1A10-B5 monoclonal antibody (mAb) (B5) binds to rhTNF alpha with a titer
      comparable to three high-affinity neutralizing mouse mAbs, when tested by ELISA.
      However, the B5 mAb binds relatively weakly to soluble rhTNF alpha. It appears to
      bind to epitopes on rhTNF alpha distinct from those bound by the mouse mAbs for
      three reasons. First, preincubation of plate-bound rhTNF alpha with mouse mAbs
      does not decrease or compete subsequent B5 mAb binding. Second, rhTNF alpha
      complexed to the mouse mAbs can still be bound by B5 mAb. Third, the mouse mAbs
      neutralize TNF alpha cytotoxicity whereas the B5 mAb does not. Binding analyses
      indicate that this human IgM autoantibody binds to both human and mouse
      recombinant TNF alpha, but not to other antigens commonly recognized by
      polyreactive natural IgM autoantibodies. The high level of amino acid identity
      between the human and mouse TNF alpha molecules suggest that the B5 mAb is
      monospecific for a given epitope shared by these two forms of TNF alpha. This
      spectrum of characteristics makes B5 a novel mAb.

PMID- 7504980
TI  - Induction of T-lymphocyte adhesion by histidine-proline-rich glycoprotein and
      concanavalin A.
AB  - Histidine-proline-rich glycoprotein (HPRG) is a plasma protein which binds to a
      specific receptor on T-lymphocytes and represses T-cell activation and
      proliferation. In the presence of Concanavalin A (Con A), HPRG causes human T
      lymphoblastic MOLT-3 cells and a fraction of normal human peripheral blood
      lymphocytes to attach to the culture dish and significantly change morphology by
      either extending processes or becoming elongated at the poles, respectively. HPRG
      and Con A are just as effective at inducing MOLT-3 attachment in a soluble or an
      immobilized form. MOLT-3 cell attachment is specific for HPRG, dose-dependent,
      and reversible in 72 hr. Only certain T-cell mitogenic lectins, Con A and
      phytohemagglutinin, are effective at stimulating adherence. Mannose, glucose,
      fucose, and N-acetylglucosamine inhibit HPRG-induced MOLT-3 cell attachment to
      different degrees, with methyl alpha-D-mannopyranoside being the most potent
      inhibitor. We propose that in vivo HPRG together with a naturally expressed
      lectin induces T-lymphocyte adhesion to initiate cell migration to sites of
      inflammation.

PMID- 7504982
TI  - The B5 monoclonal human autoantibody binds to cell surface TNF alpha on human
      lymphoid cells and cell lines and appears to recognize a novel epitope.
AB  - A human IgM monoclonal antibody (B5) recognizing human TNF alpha was established
      from peripheral blood lymphocytes by transformation with Epstein-Barr virus and
      subsequent cell fusion. The B5 monoclonal antibody (mAb) binds to cell surface
      TNF alpha (csTNF alpha) on human T cells, B cells, and monocytes. In addition,
      this autoantibody binds to csTNF alpha on a variety of lymphoid and monocyte
      lineage cell lines of human origin, as well as astrocytomas, a breast carcinoma,
      and a melanoma. Interestingly, the B5 mAb also binds to chimpanzee lymphocytes
      and to mouse T lymphoma cell line csTNF alpha. Many neutralizing mouse anti-TNF
      alpha mAbs do not exhibit comparable binding to csTNF alpha. This is consistent
      with the previous demonstration that B5 recognizes an epitope on TNF alpha
      distinct from those recognized by three neutralizing mouse anti-TNF alpha mAbs.
      B5 binding to csTNF alpha is specific since it can be inhibited by TNF alpha. No
      inhibition of B5 binding was seen by a neutralizing mouse anti-TNF alpha mAb. The
      B5 autoantibody appears to recognize the transmembrane form of TNF alpha and most
      likely also recognizes TNF alpha associated with its receptor. The unique
      specificity of this B5 autoantibody provides some additional insight into the
      complex physiology of cell surface-associated TNF alpha.

PMID- 7504983
TI  - The effect of interleukin 2 and transforming growth factor-beta 2 (TGF-beta 2) on
      the proliferation and natural killer activity of decidual CD16- CD56bright
      natural killer cells.
AB  - The present study, using flow cytometry, demonstrated that CD16- CD56bright
      natural killer (NK) cells, which are abundant in the decidua, have both
      interleukin-2 receptor alpha (IL-2R alpha) and interleukin-2 receptor beta (IL-2R
      beta). The NK activity and DNA synthesis of CD16- CD56bright NK cells were
      markedly elevated even by treatment with small amounts of IL-2. These results
      indicate that decidual CD16- CD56bright NK cells possess a high-affinity receptor
      for IL-2. Transforming growth factor-beta 2 (TGF-beta 2), which is contained in
      the decidua and is thought to serve as a major immunosuppressive factor, reduced
      the NK activity of decidual CD16- CD56bright NK cells, but it hardly affected the
      IL-2-induced augmentation of the NK activity or DNA synthesis of decidual CD16-
      CD56bright NK cells. The conclusion has therefore been reached that once IL-2 is
      produced in the decidua, the IL-2-induced potentiation of the NK activity of
      decidual CD16- CD56bright NK cells cannot be suppressed by TGF-beta 2.

PMID- 7504984
TI  - [Nursing care of esophageal carcinoma treated by local chemotherapy injection and
      microwave local heating].

PMID- 7504985
TI  - Hypothyroidism and arthritis during interferon therapy.
AB  - The development of autoantibodies during interferon therapy is frequent, but
      clinical symptoms of autoimmune disease are uncommon. We report on a female
      patient who developed arthritis with strongly positive antinuclear factor (ANA)
      and autoimmune thyroiditis while being treated with alpha 2b interferon (IFN) for
      chronic myelocytic leukaemia (CML). The arthritis subsided promptly after
      discontinuation of IFN and initiation of nonsteroidal anti-inflammatory drugs.

PMID- 7504986
TI  - Increase in fibrinogenemia in the postoperative period of open-heart surgery.
AB  - Postoperative thromboses, with no effective prevention currently available, are a
      serious complication of open-heart surgery. Conventionally, anticoagulants
      (heparin, coumarine derivatives) are used after prosthetic heart valvular surgery
      (PHVS), and antiplatelet drugs (ASA) are administered after coronary artery by
      pass graft operation (CABG)). Postoperative thrombophilia may be enhanced by an
      increase in plasma fibrinogen (FBG) levels, from 2.6 +/- 0.4 to 6.0 +/- 1.8 g/l,
      p < 0.01, as observed following open-heart surgery in CABG pts (n = 19), and from
      2.8 +/- 0.5 to 4.2 +/- 1.0 g/l, p < 0.01) in PHVS pts (n = 12) during
      postoperative days 6 to 10. This increase in FBG in both groups of pts on
      different antithrombotic regimens significantly correlated with an increase in
      others plasma proteins alpha-1-antitrypsin A1AT (r = 0.43, p < 0.01),
      coeruloplasmin, CRPL (r = 0.53, p < 0.01), orosomucoid, ORM (r = 0.37, p < 0.02),
      and with prolongation of euglobulin clot lysis time (r = 0.42, p < 0.01) during
      the 21-day postoperative period. A negative correlation was demonstrated between
      FBG and the plasma levels of transferrin, TRF (r = -0.389, p < 0.02). Whereas
      FBG, ORM, A1AT, and CRPL are referred to as "positive" acute phase proteins, TRF
      is a "negative" acute phase protein. It follows from multivariate factor analysis
      that the reactive increase in these acute phase proteins (incl.FBG) is due to one
      "common" stimulating factor during the postoperative period. The "common"
      stimulating factor also raised thrombocyte count.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7504987
TI  - The human gene for water channel aquaporin 1 (AQP1) is localized on chromosome
      7p15-->p14.
AB  - The chromosomal localization of the gene encoding aquaporin 1 (previously called
      CHIP28), which acts as a water channel in erythrocytes and in the renal proximal
      tubules and descending limbs of Henle, was determined. Southern blot
      hybridizations on chromosomal DNA of a panel of 25 different human x rodent
      hybrid cell lines localized the aquaporin 1 gene to human chromosome 7.
      Additionally, in situ hybridization on R-banded metaphase chromosomes
      sublocalized the aquaporin 1 gene (AQP1) to 7p15-->p14, and some sequence-tagged
      sites in this region were identified.

PMID- 7504988
TI  - The major histocompatibility complex influences myelin basic protein 63-88
      induced T cell cytokine profile and experimental autoimmune encephalomyelitis.
AB  - Polymorphism of the major histocompatibility complex (MHC) influences
      susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by
      myelin basic protein (MBP) in rats. Current concepts relate such influences to
      the capacity of class II molecules to present relevant peptides to autoreactive T
      cells. We have here analyzed the MHC influence on the immune response and the
      development of EAE after immunization with the immunodominant peptide MBP-63-88.
      Analysis of MHC-congenic LEWIS strains showed that RT1a, RT1c and RT1(1)
      haplotypes are permissive for disease induction, whereas RT1d and RT1u are
      resistant. All EAE responding strains showed peptide-specific proliferation and
      interferon (IFN)-gamma secretion, but no early significant tendency to express
      interleukin (IL-4) or transforming growth factor (TGF)-beta mRNA in lymphocytes
      in response to the MBP 63-88, 7 days post immunization (p.i.). Later, 14 days
      p.i., peptide-specific induction of IL-4 and TGF-beta occurred in RT1(1) rats.
      Among the EAE non-responders strains, only the RT1u rats showed an immune
      response to MBP 63-88. This response, however, was qualitatively different from
      the immune response in the EAE-susceptible strains. Thus, there was no
      proliferation and only moderate IFN-gamma production in response to peptide, but
      in contrast, a significant and early peptide-induced IL-4 and TGF-beta response
      was observed. The data suggest that the MHC-associated susceptibility to EAE is
      partly related to the ability to mount a TH1-like immune response while the MHC
      associated EAE resistance may either be related to MBP peptide non-responsiveness
      or to peptide recognition and induction of a qualitatively different and disease
      down-regulatory immune response.

PMID- 7504989
TI  - Ligation of B7 with CD28/CTLA-4 on T cells results in CD40 ligand expression,
      interleukin-4 secretion and efficient help for antibody production by B cells.
AB  - It has been extensively shown that when T cells are co-stimulated with B7-CD28
      interaction, a strong proliferative as well as cytolytic T cell response can be
      induced. In contrast, there exists only indirect evidence that the B7-CD28
      interaction is of importance for the induction of T cell helper functions in B
      cell responses. Here we have used mouse fibroblasts transfected with the human Fc
      gamma receptor type II and human B7 to address this issue. We found that T cells,
      when activated through the T cell receptor (TcR)/CD3 complex with monoclonal
      antibodies and co-stimulated by B7-CD28 interaction, can provide efficient help
      for the induction of both IgM and IgG production by resting B cells. This helper
      activity is, at least in part, mediated by the interaction between the CD40
      ligand on the T cells and CD40 on the B cells. We also demonstrate that more than
      one signal to the T cell is required for the induction of the CD40 ligand, one
      being delivered through the TcR/CD3 complex and the second by ligation of CD28
      with the B7 molecule. In addition to the induction of cognate T helper function,
      we provide evidence that co-stimulation of T cells with B7-CD28 interaction can
      result in the secretion of both Th1- and Th2-type lymphokines.

PMID- 7504990
TI  - Phenotypical and functional characterization of Fc gamma receptor I (CD64)
      negative monocytes, a minor human monocyte subpopulation with high accessory and
      antiviral activity.
AB  - Fc gamma receptor I-positive (CD64+) and Fc gamma receptor I-negative (CD64-)
      monocytes were prepared from highly purified (elutriation-derived) human
      monocytes by cytofluorograph cell sorting, and a phenotypical and functional
      dissociation of the isolated CD64+ and CD64- monocyte subsets is demonstrated.
      Surface analyses revealed that the surface antigen pattern of CD64+ monocytes
      corresponds to the phenotype of typical unseparated monocytes. In contrast, CD64-
      monocytes are characterized by high expression of major histocompatibility
      complex (MHC) class I antigens (HLA-A, -B, -C) and MHC class II antigens (HLA-DR,
      -DP, -DQ), and low expression of the monocyte-specific marker CD14 which is found
      on nearly all CD64+ monocytes. However, 75% of the CD64- cells were found to be
      esterase-positive, and 85% were positive for the the CD64- cells were found to be
      esterase-positive, and 85% were positive for the monocyte/macrophage-specific
      intracellular antigen CD68. Furthermore, CD64- monocytes show significantly
      higher expression of CD45RA and Fc gamma receptor III (CD16) than CD64+
      monocytes, but lack the natural killer cell markers CD56 and CD57. Functional
      studies showed that cells of the minor CD64- monocyte subset have a higher
      accessory cell capacity in antigen-driven T cell activation than CD64+ monocytes.
      CD64- monocytes pretreated with PPD (purified protein derivative of tuberculin)
      induced up to tentimes more interferon-gamma and also higher proliferation in
      responding autologous T cells than PPD-pretreated CD64+ monocytes. Similar
      results were obtained for T cells in mixed leukocyte reaction. Interferon-gamma
      release and proliferation of allogeneic lymphocytes were consistently higher in
      the presence of irradiated CD64- monocytes than of irradiated CD64+ monocytes.
      Furthermore, when CD64- and CD64+ monocytes were stimulated with Newcastle
      disease virus, we measured an up to 67-fold higher interferon-alpha release from
      CD64- than from CD64+ monocytes, indicating a higher anti-viral capacity of this
      subset. CD64- monocytes showed lower activity in the phagocytosis of unopsonized
      particles and also lower zymosan- or latex-induced chemiluminescence than CD64+
      monocytes. These findings indicate that CD64- monocytes, although comprising only
      less than 10% of all peripheral blood monocytes, represent a monocyte
      subpopulation efficiently interacting in vitro with T cells and, additionally,
      are the major source of interferon-alpha.

PMID- 7504991
TI  - Identification of new B cell epitopes in the sera of rheumatoid arthritis
      patients using a random nanopeptide phage library.
AB  - A random nanopeptide phage library was used to screen a pool of immunoglobulin
      fractions obtained from rheumatoid arthritis (RA) patients. After three rounds of
      panning, random individual phages were selected by their capacity to react with
      individual sera from RA patients. By sequencing the inserts corresponding to the
      peptides displayed on the surface of the phages, we found that phages displaying
      particular peptides were overrepresented in the selected libraries. The peptides
      displayed by these phages were: pep1 = Ala-Asp-Gly-Gly-Ala-Gln-Gly-Thr-Ala; pep2
      = Pro-Gly-Pro-Ser-Arg-Ala-His-Phe-Leu; pep3 = Leu-Ser-Ser-Arg-Glu-Pro-Gln-Ala
      Arg; pep4 = Arg-Leu-Thr-Arg-Glu-Leu-Tyr-Ala-Gln and pep5 = Tyr-Thr-Gln-Lys-His
      Gln-Ala. The percentage of sera positive for pep1 was higher in RA patients as
      compared to the normal adults (p < 0.0004) and the reacting antibody was mainly
      of IgG isotype. The specificity of binding to the phage displaying pep1 was
      confirmed by competition experiments using both isolated phages and a synthetic
      peptide. Interestingly, a mutated phage displaying only Ala-Asp-Gln-Gly-Thr-Ala
      had no significant reactivity with the sera, indicating that the amino acids (Gly
      Gly-Ala) of pep1 are the vital for the binding. Taken together this study
      demonstrates that it is possible to select specific ligands from a random phage
      library using sera from RA patients. In addition, this approach could be useful
      for identifying peptide antigens that might be part of causitive agents in
      autoimmune diseases.

PMID- 7504992
TI  - Activation of MAP kinases, pp90rsk and pp70-S6 kinases in mouse mast cells by
      signaling through the c-kit receptor tyrosine kinase or Fc epsilon RI: rapamycin
      inhibits activation of pp70-S6 kinase and proliferation in mouse mast cells.
AB  - The high-affinity receptor for IgE, Fc epsilon RI, represents the major cell
      surface structure through which mast cells express immunologically specific
      secretory function. By contrast, the stem cell factor receptor (SCFR), which is
      encoded by c-kit, is essential for normal mast cell development. The signaling
      pathways initiated by the stimulation of mast cells through the Fc epsilon RI,
      which lacks intrinsic kinase activity, and the SCFR, a member of the receptor
      tyrosine kinase family, generally have been regarded to be distinct. We report
      here that mouse mast cells stimulated either with SCF or with IgE and specific
      antigen exhibit a remarkably similar pattern of activation of mitogen-activated
      protein kinases (MAPK), 90 kDa-S6 kinases (pp90rsk), and pp70-S6 kinases (pp70
      S6K). These results indicate that all three families of protein kinases are
      associated with the cell surface receptor-dependent activation of secretion, as
      well as proliferation, in mast cells. We also show that the immunosuppressant
      rapamycin, but not FK506, can inhibit both SCF-dependent pp70-S6 kinase
      activation and SCF-dependent proliferation in mouse mast cells, without
      suppressing IgE- and antigen-dependent mediator release. These findings suggest
      that the activation of pp70-S6 kinase represents an important link in the
      stimulation of cell proliferation by SCF. Our results also indicate that the
      intracellular signaling pathways initiated by stimulation of mast cells through
      the Fc epsilon RI or the SCFR exhibit more overlap than has previously been
      appreciated.

PMID- 7504993
TI  - A role for antigen-presenting cells and bacterial superantigens in reversal of
      human T lymphocyte anergy.
AB  - The induction of anergy in T lymphocytes generates T cells incapable of
      proliferation in response to a conventional antigenic stimulus. To investigate
      the induction and maintenance of anergy in human T cells, we used T cell-T cell
      presentation of myelin basic protein (MBP) or MBP synthetic peptides to induce
      anergy in vitro. Although anergic T cells responded normally to interleukin-2 (IL
      2), these T cells did not produce IL-2 or IL-4 when peripheral blood mononuclear
      cells presented MBP or MBP peptides. Proliferation of anergic T cells was reduced
      by greater than 95% compared to nonanergic, control T cells. However, when
      autologous B cell lines were used to present MBP, anergy was partially reversed
      with a proliferation response about 50% of nonanergic levels. Bacterial
      superantigens also partially restored proliferation in anergic T cells following
      presentation by either B cell lines or macrophage isolated from peripheral blood
      mononuclear cells. Anergic, MBP-reactive T cells fully retained antigen-specific
      cytolytic activity against both B cell and T cell targets presenting MBP. These
      results suggest that T cell proliferative anergy may be reversible with both the
      type of antigen-presenting cell and superantigens potentially contributing to the
      initiation or maintenance of an autoimmune response.

PMID- 7504994
TI  - Deficient antigen processing of a protein quaternary structure can be overcome by
      receptor-mediated uptake.
AB  - Human chorionic gonadotropin (hCG) is a dimer of non-covalently associated alpha
      (hCG-alpha) and beta (hCG-beta) subunits. This molecule was used to study whether
      receptor-mediated uptake influences the presentation of a protein quaternary
      structure. Unprimed splenocytes and a B cell lymphoma were capable of presenting
      only the free (hCG-alpha) but not the combined (hCG) alpha subunit to hCG-alpha T
      cell hybridomas, while hCG-alpha-primed lymph node cells (LNC) responded to both
      hCG-alpha and hCG. As antigen (Ag)-specific antigen-presenting cells (APC)
      present in the hCG-alpha-primed LNC population may be potentially effective for
      presenting hCG, we investigated the role of specific Ag capture, through mIg and
      Fc gamma R, in the processing and presentation of hCG and hCG-alpha to HAG5, a T
      cell hybridoma directed against the immunodominant region (amino acids 61-81) of
      hCG-alpha. Results showed that only B cells bearing membrane immunoglobulin
      capable of recognizing hCG-alpha and hCG, and present in hCG-alpha-primed mice,
      were extremely effective in presenting the free as well as the combined alpha
      subunit. The effect of FcR-mediated uptake was analyzed using a B cell line
      transfected with the Fc gamma RII-B2 gene to present immune complexes of either
      hCG-alpha or hCG. We found that hCG-alpha and hCG were presented equally well,
      whatever the Ag-binding site of each antibody to hCG or its alpha subunit. Using
      HBG 6, an hCG-beta T cell hybridoma, we performed similar experiments with the Fc
      gamma RII-B2 cell line and determined that the potentiation of hCG presentation
      to HBG 6 was similar to that observed with HAG 5. Then kinetic experiments were
      performed to examine the effect of Ag uptake through FcR on processing. Results
      demonstrated that the uptake pathway drastically influenced the expression of
      alpha T cell determinants in the alpha/beta dimer. In addition, treatment with
      cycloheximide, a protein synthesis inhibitor, only impaired the ability of APC to
      present specifically captured Ag. Thus, the processing pathway for specifically
      captured Ag might be different from the pathway used to process nonspecifically
      captured Ag. This observation might explain why receptor-enhanced uptake bypasses
      the inefficient processing of the hCG quaternary structure and enables similar
      efficiency in the presentation of alpha and beta T cell specificities. These
      findings provide new insight into the antigenicity of oligomeric molecules, which
      is modified whether antigen capture is specific or not.

PMID- 7504995
TI  - Antigen-presenting human T cells and antigen-presenting B cells induce a similar
      cytokine profile in specific T cell clones.
AB  - One of the factors that may influence the cytokine secretion profile of a T cell
      is the antigen-presenting cell (APC). Since activated human T cells have been
      described to express major histocompatibility complex (MHC) class II molecules as
      well as costimulatory molecules for T cell activation, like e.g. ICAM-1, LFA-3
      and B7, they might play a role as APC and be involved in the regulation of T
      Tcell interactions. To define further the role of T cells as APC we tested their
      capacity to induce proliferation and cytokine production in peptide- or
      allospecific T cell clones and compared it with conventional APC, like B
      lymphoblasts (B-LCL) or HTLV-1-transformed T cells, or with non-classical APC,
      like activated keratinocytes or eosinophils. CD4+, DP-restricted T cell clones
      specific for a tetanus toxin peptide (amino acids 947-967) and CD4+, DR
      restricted allospecific T cell clones produced interleukin (IL)-2, IL-4, tumor
      necrosis factor-alpha and interferon-gamma (IFN-gamma) after phorbol 12-myristate
      13-acetate and ionomycin stimulation and a more restricted cytokine pattern after
      antigen stimulation. Dose-response curves revealed that the antigen-presenting
      capacity of activated, MHC class II+, B7+ T cells was comparable to the one of B
      LCL. Both APC induced the same cytokine profile in the T cell clones despite a
      weaker proliferative response with T cells as APC. Suboptimal stimulations
      resulted in a lower IFN-gamma/IL-4 ratio. Cytokine-treated, MHC class II+
      keratinocytes and eosinophils differed in the expression of adhesion molecules
      and their capacity to restimulate T cell clones. The strongly ICAM-1-positive
      keratinocytes induced rather high cytokine levels. In contrast, eosinophils,
      which express only low densities of MHC class II and no or only low levels of
      adhesion molecules (B7, ICAM-1 and LFA3), provided a reduced signal resulting in
      a diminished IFN-gamma/IL-4 ratio. We conclude that non-classical APC differ in
      their capacity to restimulate T cell clones, whereby the intensity of MHC class
      II and adhesion molecules (B7, ICAM-1) expressed seems to determine the efficacy
      of this presentation.

PMID- 7504996
TI  - Noradrenergic regulation of c-jun expression in the rat pineal gland in culture:
      positive and negative components.
AB  - One component of the nocturnal changes in cellular immediate-early gene
      expression in the rat pineal gland is a decrease in c-jun expression, mediated
      through beta-adrenoceptors. An in vitro study of the intracellular mechanisms
      which control c-jun expression has now shown that a norepinephrine-induced
      increase in c-jun mRNA levels in organ-cultured pineals is differentially
      modulated by protein kinase inhibitors; N-(2-guanidinoethyl)-5
      isoquinolinesulfonamide (HA-1004) potentiated the response; however, in the
      presence of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a significant
      decrease in c-jun mRNA was found. Treatment with HA-1004 alone elevated the level
      of c-jun mRNA, H-7 alone was without effect. Forskolin together with 3-isobutyl-1
      methylxanthine suppressed c-jun, whereas phorbol 12,13-dibutyrate raised c-jun
      mRNA levels. The results demonstrate opposing pathways for c-jun regulation in
      the pineal gland, and indicate that the nocturnal attenuation of c-jun expression
      involves selective activation of a negative pathway which may be linked to cAMP.

PMID- 7504997
TI  - Effect of purinergic receptor antagonists suramin and theobromine on tumor
      induced angiogenesis in BALB/c mice.
AB  - The purinergic receptor antagonists suramin (SRN) and theobromine (TBR) were
      examined for their anti-angiogenic activity in BALB/c mice. SRN or TBR were
      subcutaneously administered to BALB/c mice in doses of 1-125 mg/kg body weight on
      days 0, 1 and 2 after intradermal inoculation of E14/W lung carcinoma cells. It
      was shown that SRN and TBR inhibited tumor-related angiogenesis. Accordingly, it
      may be suggested that purinoceptor antagonists may inhibit neovascularization in
      tumor growth and metastasis.

PMID- 7504998
TI  - Mechanoelectrical feedback in cardiac myocytes from stretch-activated ion
      channels.
AB  - Stretch-activated ion channels (SAC's) in cardiac myocytes from neonatal rats
      were studied in cell-attached patches. Stretch of membrane patches by suction in
      the recording pipette caused the triggering of action potentials that were
      recorded as action currents (AC's). The significance of a temporal correlation
      between SAC open probability and AC's was tested using the Kolmogorov-Smirnov and
      Poisson distributions. It was shown that the 50-ms epoch immediately preceding
      the action current had unique kinetics and represented a peak in SAC open
      probability (p < 0.001). Thus it appears that current from a small number of
      SAC's injects sufficient charge (0.2 pC during 50 ms) to trigger action
      potentials in myocytes. These data strengthen the hypothesis that passive
      mechanical stretch of myocardium can be arrhythmogenic.

PMID- 7504999
TI  - Analysis of a human monoclonal antibody reactive with multiple Plasmodium
      falciparum antigen repeat sequences using a solid phase affinity assay.
AB  - A solid-phase affinity assay was set up for the determination of the affinity of
      the interaction between the human monoclonal antibody (mAb) 33G2 and peptides
      corresponding to repeated sequences in three blood stage antigens of the malaria
      parasite Plasmodium falciparum. The epitope of this mAb is of interest due to the
      parasite blocking capacity of the mAb. Previous studies with PEPSCAN have defined
      the minimal epitope for the mAb as the pentapeptide VTEEI, a sequence frequently
      found in antigen Pf332. In the previous study, epitopes responsible for the cross
      reactivity of the mAb with antigens Pf155/RESA and Pf11.1 were also identified.
      In the affinity assay described herein, the mAb was coated on a solid phase and
      binding of a labelled peptide was displaced by homologous or heterologous
      peptides. The affinity of peptides corresponding to Pf332 increased with
      increasing length, and the highest affinity was displayed by a dimer (23 amino
      acids) of a Pf332 repeat (K = 1.9 x 10(8) M-1). Peptide length did not influence
      the binding of peptides corresponding to the Pf155/RESA and Pf11.1 repeats, which
      had lower affinities comparable to that of the shortest Pf332 octapeptide (K =
      2.2 x 10(4) M-1). Only peptides containing binding sites as defined by PEPSCAN
      analysis showed a measurable binding. When using peptides as inhibitors in
      peptide ELISA, binding correlated with the affinity of the peptides, but only the
      high affinity peptides were inhibitory. In contrast, a poor correlation was found
      when peptides were used directly for coating in ELISA.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7505000
TI  - In vitro immunomodulatory effects of pentoxifylline.
AB  - Pentoxifylline (PTX), a methylxanthine derivative and phosphodiesterase
      inhibitor, is known to influence production and/or function of some cytokines. We
      examined the effect of PTX on the in vitro expression of cytokine genes using
      endotoxin- or phytohaemagglutinin (PHA)-stimulated human blood mononuclear cells.
      The expression of tumour necrosis factor (TNF)alpha, TNF beta interleukin (IL)-2
      and interferon (IFN)gamma was inhibited by PTX in a dose-dependent manner,
      whereas expression of IL-1 alpha, IL-1 beta, and IL-6 was unaffected at
      concentrations up to 300 microM of PTX. The amount of TNF beta mRNA in PHA
      stimulated blood mononuclear cells was reduced by PTX. Finally, PTX stimulated
      PHA-induced cell proliferation whereas antigen-induced cell proliferation was
      inhibited in the presence of PTX. The PTX analogues HWA-138 and A-802715
      inhibited TNF alpha mRNA expression from endotoxin-stimulated mononuclear cells.
      These data suggest that PTX-analogues affect the in vitro immune response at
      different target points and that the response depends upon the respective
      triggering mechanism(s).

PMID- 7505001
TI  - The presence of CD5LOW+NK cells in normal controls and patients with pulmonary
      tuberculosis.
AB  - CD5 antigen is present on all normal alpha beta T cells and some B cells. Human
      NK cells do not usually express CD5 antigen, but we found a subset of CD5LOW+
      (low density of CD5) NK cells in some patients with pulmonary tuberculosis.
      Unlike CD5-NK cells, most CD5LOW+NK cells had HLA-DR. We observed few CD5LOW+NK
      cells in the normal controls and some in the large granular lymphocyte (LGL)
      population purified by Percoll density centrifugation. Sorted CD5LOW+NK
      populations were LGL. The CD5LOW+NK cells had high lytic activity on K562 cells
      in a 4-h 51chromium release assay. Our results indicate that there is a
      previously unidentified subset of NK cells.

PMID- 7505002
TI  - A monoclonal antibody against human decay-accelerating factor (DAF, CD55), D17,
      which lacks reactivity with semen-DAF.
AB  - Human decay-accelerating factor (DAF, CD55) is a phosphatidyl inositol-anchored
      glycoprotein consisting, from the N-terminus, of 4 short consensus repeats (SCR),
      a Ser/Thr (ST)-rich region providing O-glycosylation sites, and the membrane
      anchoring unit. A mAb, named D17, was raised against purified erythrocyte-DAF.
      This mAb recognized DAF on blood cells and most cell lines as determined by flow
      cytometry and immunoblotting. Its reactivity was similar to but weaker than that
      of two other well-characterized mAbs to DAF, IA10 (seeing an epitope within SCR1)
      and 1C6 (seeing an epitope within SCR3). The reactivity of D17 with erythrocyte
      DAF became increased by treatment with sialidase/O-glycanase, suggesting that its
      epitope is located close to the O-glycosylation sites, probably within the ST
      rich region or SCR4. D17 barely blocked the decay-accelerating activity of DAF.
      Using the three mAbs, tissue-associated and soluble forms of DAF were identified
      by SDS-PAGE/immunoblotting and immunohistochemical staining. IA10 and 1C6
      recognized a 50 kDa protein in spermatozoa lysate and two proteins of Mr 70 and
      55 kDa, respectively, in seminal fluid. These represented membrane-associated and
      soluble forms of DAF, which were neither recognized by mAb against membrane
      cofactor protein (MCP, CD46) and C3b/C4b receptor (CR1, CD35) nor by non-immune
      IgG. In contrast to IA10 and 1C6, D17 did not recognize either spermatozoa-DAF or
      seminal plasma-DAF, or the deglycosylated or untreated forms of them.
      Immunohistochemical analysis showed that testis was stained with IA10 but not
      with D17.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505003
TI  - Localization of T-cell determinants on bovine beta-lactoglobulin.
AB  - T-cell determinants of bovine beta-lactoglobulin (beta-LG) in BALB/c(H-2d),
      C57BL/6(H-2b) and C3H/He(H-2k) mice were identified using a set of overlapping
      synthetic peptides encompassing the entire primary structure of the protein.
      Lymph node cells from mice immunized with beta-LG were subjected to cell
      proliferation assay in the presence of these peptides and uptake of 3H-labeled
      thymidine was measured. Determinant regions were indicated to lie in residues 42
      56, 62-76 and 139-153 in BALB/c mice, residues 11-26, 72-86, 100-113 and 119-133
      in C57BL/6 mice, residues 72-86, 91-104, 129-143 and 139-153 in C3H/He mice. Some
      of these fragments included the antigenic motifs predicted by hypotheses
      according to amphipathicity and sequential patterns of peptides. We reported
      elsewhere that residues 42-56 and 72-86 represent one of the B-cell antigenic
      determinants in BALB/c and C3H/He, respectively. These peptides serve as good
      models of colinear T- and B-cell determinants as they contain both of T- and B
      cell determinants.

PMID- 7505004
TI  - Expression of an early myelopoietic antigen (CD33) on a subset of human umbilical
      cord blood-derived natural killer cells.
AB  - A new subset of natural killer (NK) cells was identified in human umbilical cord
      blood. This subset of CD56+/CD3- NK cells co-expressed the CD33 antigen, which is
      present on early hematopoietic progenitors confined to the myeloid lineage. The
      percentage of the CD56+/CD33+ cells among the CD56+/CD3- NK cells was 7.9 +/-
      6.6% (n = 27) with a range of 1.4-25.5% and a considerable individual
      variability. Additionally, the majority of freshly isolated CD56+/CD33+ cells co
      expressed the CD2 and CD7 antigen, a minor proportion co-expressed the CD8
      antigen but essentially all of the cells stained negative for CD16 and CD57.
      Morphological analysis of the CD56+/CD33+ cells showed the features of large
      agranular lymphocytes. From some of the samples, the CD56+/CD33+ NK cells were
      cultivated and expanded in vitro by incubation of the cells with interleukin 2
      (IL-2) for up to 50 days. Morphological analysis of the cultured CD56+/CD33+
      cells showed the features of large granular lymphocytes (LGL). The IL-2-expanded
      CD56+/CD33+ NK cells showed only a low cytolytic activity against K562 target
      cells, whereas most of the NK activity of the expanded cells was contributed by
      the CD56+/CD33- NK cells.

PMID- 7505005
TI  - A common T-cell epitope between human thyroglobulin and human thyroid peroxidase
      is related to murine experimental autoimmune thyroiditis.
AB  - We have investigated functional common T-cell epitopes between human
      thyroglobulin (hTg) and human thyroid peroxidase (hTPO) in mice. Four hTg
      peptides, Tg-P1, Tg-P2, Tg-P3 and Tg-P4, in which 5 amino acid residues are
      identical to those of hTPO, and 1 hTPO peptide, TPO-P4 relevant to Tg-P4, were
      prepared. Among these peptides, only Tg-P4 (residues 2730-2743) and TPO-P4
      (residues 118-131) were highly antigenic and both peptides shared the common T
      cell epitope. In addition, when the spleen cells from mice immunized with mouse
      Tg (mTg) were restimulated in vitro by Tg-P4 or TPO-P4 as well as by mTg, these
      cells transferred thyroiditis to naive recipient mice. These findings indicate
      that this common T-cell epitope between hTg and hTPO is immunogenic and related
      to the development of murine experimental autoimmune thyroiditis.

PMID- 7505006
TI  - MMPs and proteinase inhibitors in the human aqueous humor.
AB  - PURPOSE: This study was performed to examine the gelatinolytic and caseinolytic
      activities and the levels of two proteinase inhibitors, alpha 1-proteinase
      inhibitor (alpha 1-antitrypsin) and alpha 2-macroglobulin, in the human aqueous
      humor. METHODS: Aqueous humor samples were collected during elective surgery in
      patients with cataracts. Zymography with gelatin- and casein-containing gels was
      performed. The inhibitors were examined by Western blot analyses, enzyme-linked
      immunosorbent assay, and dot blot assays. RESULTS: The aqueous humor contained a
      major band of gelatinolytic activity at a molecular weight of 66 kD and minor
      bands at 125, 95, and 62 kD. These gelatinases were inhibited by 10 mM
      ethylenediaminetetraacetic acid (EDTA) or 1,10-phenanthroline. After extended
      incubation (48 hours), zymography on casein-containing gels showed proteinase
      bands with molecular weights in the 80- to 84-kD range. Additional bands at 68
      and 48 kD also were observed. All the caseinase activities were inhibited by 10
      mM phenylmethylsulfonyl fluoride and 1 microgram/ml aprotinin. No inhibition was
      observed with 5 mM EDTA, 5 microM E-64, or 1 microM pepstatin. These results
      indicated that the caseinases are serine proteinases. Western blot analysis
      showed a 53-kD alpha 1-proteinase inhibitor band in the aqueous humor. The
      concentration was 32.2 +/- 9.9 micrograms/ml, constituting approximately 15% of
      the total protein. A 360-kD protein band immunoreactive to anti-alpha 2
      macroglobulin also was detected. Its level in the aqueous humor was 3.2 +/- 1.3
      micrograms/ml. CONCLUSIONS: The gelatinases, serine-like proteinases, and
      proteinase inhibitors found in the aqueous humor may participate in the
      remodeling of extracellular matrices in the trabecular meshwork and other tissues
      bordering the anterior chamber.

PMID- 7505007
TI  - Differential expression of the complement regulatory proteins in the human eye.
AB  - PURPOSE: The presence of complement activation products in the human eye during
      infection or inflammation has been well described. During complement activation
      the host must be protected from attack against self tissue; this is achieved by
      three membrane-bound complement regulatory proteins: membrane cofactor protein
      (MCP, CD46), decay accelerating factor (DAF, CD55), and membrane attack complex
      inhibiting protein (CD59). This study was undertaken to analyze the expression of
      these proteins in the normal human eye. METHODS: Tissues were sectioned by
      cryostat and both polyclonal and monoclonal antibodies to MCP, DAF, and CD59 were
      used. Control stains were performed with nonrelevant antibodies of the same
      immunoglobulin subclass and normal rabbit serum as well as by omission of the
      primary and secondary antibodies. RESULTS: All three proteins were found to be
      differentially expressed in the human eye. With anti-MCP, strong staining of the
      corneal epithelium and weak staining of the corneal keratocytes in stroma and
      photoreceptor cells was observed. Staining with anti-DAF was very strong in the
      corneal epithelium and the ciliary body and moderate in the corneal stroma
      (keratocytes) and iris. In contrast, anti-CD59 stained very strongly in the
      corneal epithelium, corneal stroma (keratocytes), iris, choroid, and all layers
      of the retina, and moderately in the ciliary body. CONCLUSIONS: Identification of
      MCP, DAF, and CD59 in the human eye provides evidence that a regulatory system
      exists to protect these cells from destruction by complement-activating events.
      It remains to be determined if other more specialized functions exist for these
      proteins, especially in the case of CD59 because of its extensive expression in
      the retina.

PMID- 7505008
TI  - Expression of endothelial and leukocyte adhesion molecules interacellular
      adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in the
      bronchial mucosa in steady-state and allergen-induced asthma.
AB  - BACKGROUND: Interactions between cell adhesion molecules and their ligands are an
      integral part of inflammatory processes and may have direct relevance to the
      pathology of asthma. METHODS: Immunostaining with antibodies to cell adhesion
      molecules was performed on bronchial biopsy specimens from persons with intrinsic
      and extrinsic asthma, normal nonasthmatic control subjects, and patients with
      asthma after allergen challenge. RESULTS: There was constitutive expression of
      intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion
      molecule-1 (VCAM-1) in patients with intrinsic and extrinsic asthma and in
      control subjects. Compared with control subjects, ICAM-1 and E-selectin staining
      in the submucosa was greater in the intrinsic asthmatic group for intensity (p <
      0.02, p < 0.05) and extent (p < 0.01, p < 0.05) of staining, respectively. No
      differences were observed between patients with extrinsic asthma and normal
      control subjects, and VCAM-1 expression did not differ among the groups.
      Epithelial expression of ICAM-1 was more frequent in patients with asthma
      compared with normal control subjects (p < 0.05). Compared with diluent
      challenge, bronchial biopsy specimens obtained 24 hours after allergen challenge
      revealed no significant differences in intensity or extent of staining for ICAM
      1, E-selectin, or VCAM-1. After allergen challenge, the intensity and extent of
      both VCAM-1 and ICAM-1 expression correlated significantly with the number of
      eosinophils (cells positive for major basic protein). Epithelial ICAM-1
      expression was more frequently observed after allergen challenge than after
      diluent challenge (p < 0.02). CONCLUSIONS: The data suggest a complex pattern of
      regulation for ICAM-1, E-selectin, and VCAM-1 in vivo, where they may reflect the
      degree of ongoing inflammation in asthma.

PMID- 7505009
TI  - In vitro cytotoxicities of 1,4-naphthoquinone and hydroxylated 1,4
      naphthoquinones to replicating cells.
AB  - Using the human hepatoma cell line, HepG2, and the BALB/c mouse fibroblast cell
      line, 3T3, as the bioindicators in the neutral red cytotoxicity assay, the effect
      of hydroxyl substitution on the toxicity of 1,4-naphthoquinone was studied. The
      sequence of potency for the quinones was 5,8-dihydroxy-1,4-naphthoquinone > 5
      hydroxy-1,4-naphthoquinone > 1,4-naphthoquinone >> 2-hydroxyl-1,4-
      naphthoquinone. Pretreatment of the cells with dicoumarol, an inhibitor of DT
      diaphorase, enhanced the cytotoxicity of 1,4-naphthoquinone but not of the
      hydroxylated naphthoquinones. Pretreatment of the BALB/c cells with buthionine
      sulfoximine, an inhibitor of glutathione synthesis, enhanced the sensitivity of
      the cells to all the hydroxylated naphthoquinones but not to 1,4-naphthoquinone.
      A similar pretreatment of the HepG2 cells with buthionine sulfoximine enhanced
      the toxicity of the 2-hydroxy- and 5,8-dihydroxy-1,4-naphthoquinones but not of 5
      hydroxy-1,4-naphthoquinone or of 1,4-naphthoquinone. Some differences were noted
      in the responses to the hydroxylated 1,4-naphthoquinones between buthionine
      sulfoximine-treated replicating cells and buthionine sulfoximine-treated isolated
      rat hepatocytes, a nonreplicating cell in culture. The use of a replicating cell
      system in studying the mechanisms of the cytotoxicity of quinones may be an
      important adjunct to studies using the isolated rat hepatocytes, which is the
      standard model system.

PMID- 7505010
TI  - Purification of monoclonal antibodies with light-chain heterogeneity produced by
      mouse hybridomas raised with NS-1 myelomas: application of hydrophobic
      interaction high-performance liquid chromatography.
AB  - Monoclonal antibodies (mAbs) of IgG1 class produced by hybridomas raised with NS
      1 myelomas, which were purified homogeneously by anion-exchange high-performance
      liquid chromatography (HPLC), contained two types of immunoglobulin light (kappa)
      chain. Since NS-1 myeloma synthesizes the light (kappa) chain, the mAb was
      presumed to be the mixture of hybrid mAbs formed by the random association of
      heavy (gamma l) and light chains from antigen-immunized spleen cells and light
      chain from NS-1 cells. Hydrophobic interaction HPLC using TSKgel Phenyl-5PW was
      applicable to separate 3 species of hybrid mAb from mAb fractions obtained by
      anion-exchange HPLC. mAbs in the fractions were adsorbed onto the gel
      equilibrated with phosphate-buffered saline containing 1 M ammonium sulfate and
      eluted by reducing the concentration to 0 M. The hybrid mAbs were purified
      separately. The hydrophobic interaction HPLC could discriminate a small
      difference in hydrophobicity between kappa chains from spleen and NS-1 cells. The
      immunoreactivities of hybrid mAb bearing light chains only from spleen cells and
      that bearing those from both spleen and NS-1 cells were almost the same, and
      hybrid mAb bearing light chains derived only from NS-1 cells showed a relatively
      lower immunoreactivity than the others. The method described here could be useful
      for purification of hybrid mAbs.

PMID- 7505011
TI  - Solution structure of lariat RNA by 500 MHz NMR spectroscopy and molecular
      dynamics studies in water.
AB  - A 500 MHz NMR study of the lariat RNA tetramer 1 and pentamer 2 mimicking the
      naturally occurring lariat RNA is reported. The conformational properties of 1
      and 2 were compared with those of a linear branched RNA tetramer 3, which show
      that the conformational features of the two lariat RNAs, 1 and 2, are quite
      constrained and significantly different from those observed for the linear
      branched RNA tetramer 3. The conformation of all sugar residues forming the
      lariat ring in 1 and 2 are locked in a rigid South-type conformation. All
      residues in both lariat RNAs have a high population of gamma+ (67-85%) and beta t
      (95-100%) rotamers except guanosine where the gamma+ population is low. The
      conformation around the glycosidic bond is anti for all residues except for
      guanosine where NOE data indicates an equilibrium of syn<-->anti. In both lariat
      RNAs, 1 and 2, the temperature dependent 1H and 31P chemical shifts as well as
      the oligomerization shifts, with respect to adenosine 2',3',5'-triethyl-phosphate
      (Sund et al., 1992, Tetrahedron 48, 695) suggests that the 3'-->5' linked U4 or
      C4 residue is stacked on guanosine. Subsequently, 1H-1H, 1H-31P and 13C-31P
      coupling constants derived torsional constraints were used for molecular dynamics
      study in water with counter sodium ions for a total of 226 ps. The MD simulations
      were first carried out with harmonic torsional constraints which were derived
      from J couplings (0-86 ps) and then completely without constraints (96-226 ps).
      The lack of any major changes in the conformation of the two lariat-RNA
      structures upon releasing the NMR constraints indicate that the conformers
      generated in the MD simulation in water agree well with the structural features
      suggested by experimental observables. This means that the ensemble of conformers
      generated during the MD trajectory of 226 ps are not artificially held in these
      conformations due to the NMR constraints, suggesting that these conformers can be
      considered to be good representatives of the actual NMR observed solution
      structures.

PMID- 7505012
TI  - Hyaluronic acid-induced lymphocyte signal transduction and HA receptor
      (GP85/CD44)-cytoskeleton interaction.
AB  - The purposes of this study are to characterize the binding of hyaluronic acid
      (HA) to mouse T lymphoma cells, to measure changes in intracellular Ca2+ after HA
      binding, to elucidate the interaction between the HA receptor, GP85(CD44), and
      ankyrin in the membrane skeleton, and finally to correlate these events with HA
      receptor patching/capping and cell adhesion to HA. First, we established an in
      vivo assay using [3H]HA to measure the binding of HA to mouse T lymphoma cells,
      and found that the binding of [3H]HA to these cells is readily inhibited by the
      addition of anti-GP85(CD44) antibody suggesting that GP85(CD44) is the HA
      receptor. Next, we examined various signal transducing events that occur after HA
      binds to its receptor on mouse T lymphoma cells. The results of these studies
      indicate that the concentration of intracellular Ca2+ (as measured by Fura-2
      fluorescence) begins to increase within seconds, and reaches a maximal level 5
      min after the addition of HA to the cells. After this increase of intracellular
      Ca2+, HA induces both its receptors, GP85(CD44), to form patched/capped
      structures, and cell adhesion to HA-coated plates. Furthermore, we have
      determined that GP85(CD44) binds directly and specifically to ankyrin (Kd
      approximately 1.94 nM) in a saturable manner; and that ankyrin is preferentially
      accumulated underneath the HA-induced GP85(CD44) capped structures. The Ca2+
      ionophore, ionomycin, was found to stimulate HA-induced receptor capping and
      adhesion while EGTA (a Ca2+ chelator), nefedipine/bepridil (Ca2+ channel
      blockers), W-7 (a calmodulin antagonist), and cytochalasin D (a microfilament
      inhibitor), but not colchicine (a microtubule disrupting agent), inhibit HA
      induced receptor redistribution and adhesion to HA-coated plates. These findings
      strongly suggest that ankyrin plays an important role in linking the HA receptor,
      GP85(CD44), to the membrane-associated actomyosin contractile system during
      hyaluronic acid-mediated lymphocyte activation.

PMID- 7505013
TI  - CD44 expression on activated B cells. Differential capacity for CD44-dependent
      binding to hyaluronic acid.
AB  - CD44 expression and the functional capacity for CD44-dependent binding of
      hyaluronic acid (HA) were analyzed on unstimulated B cells and on B cells
      stimulated with a variety of polyclonal B cell activators. Whereas essentially
      all LPS-activated and anti-IgD-dextran-activated B cells and a subpopulation of
      IL-5-activated B cells expressed increased levels of cell surface CD44 relative
      to unstimulated B cells, only IL-5-activated CD44hi B cells constitutively bound
      to FITC-conjugated hyaluronic acid (FITC-HA). Preincubation of LPS or anti-IgD
      dextran-activated B cells with the CD44-specific mAb IRAWB14.4 (IRA) induced a
      high degree of FITC-HA binding in these populations; preincubation of
      unstimulated B cells with this CD44-specific mAb induced minimal FITC-HA binding.
      In contrast, preincubation with mAb IRA failed to induce FITC-HA binding by the
      IL-5-activated CD44lo B cell subset. Neither the amount of constitutive FITC-HA
      binding nor the level of IRA-inducible FITC-HA binding correlated simply with the
      overall level of CD44 expressed by the different B cell populations. Biochemical
      analysis of immunoprecipitated CD44 molecules revealed that relative to CD44
      isolated from all other populations examined, CD44 isolated from IL-5-activated B
      cells was of a lower molecular weight. Treatment with N-Glycanase eliminated this
      observed difference in molecular weight, indicating that it reflected differences
      in N-glycosylation of CD44 on activated B cells. Polymerase chain reaction
      analysis of amplified cDNA showed that each B cell population expressed a common
      dominant CD44 mRNA. These findings suggest that post-translational modification
      of CD44 and/or differential association of CD44 with other cellular components
      plays a critical role in activation-specific ligand binding by CD44.

PMID- 7505014
TI  - Expression of GlyCAM-1, an endothelial ligand for L-selectin, is affected by
      afferent lymphatic flow.
AB  - The interaction of naive, L-selectin-bearing lymphocytes with counterreceptors on
      the surface of high endothelial venules (HEV) is the initial step in the
      extravasation of these cells from the bloodstream into the peripheral lymph node.
      Recently, two sulfated glycoprotein ligands, 50 and 90 kDa, respectively, have
      been identified as ligands for L-selectin using an L-selectin-IgG chimera. cDNA
      cloning of one of these molecules, the 50-kDa sulfated glycoprotein
      (glycosylation-dependent cell adhesion molecule 1 [GlyCAM-1]), has shown it to be
      a mucinlike scaffold that presents a carbohydrate ligand(s) to the lectin domain
      of L-selectin. Herein, we analyze the factors that might regulate the expression
      of these ligands. Ligation of afferent lymphatics results in a complete loss of
      the mRNA for GlyCAM-1. In addition, L-selectin-mediated adhesion, as inferred by
      binding of an L-selectin-IgG chimera, is also lost on interruption of afferent
      flow. It thus appears that a soluble and/or cellular component(s) of afferent
      lymph regulates the expression of GlyCAM-1 mRNA and the resultant HEV
      adhesiveness for lymphocytes.

PMID- 7505015
TI  - Bacterial superantigens induce rapid and T cell receptor V beta-selective down
      regulation of L-selectin (gp90Mel-14) in vivo.
AB  - Upon challenge of mice with bacterial superantigens such as staphylococcal
      enterotoxin B, several facets of TCR V beta-selective acute T-cell alterations
      can be observed, which include acute T cell priming, and systemic lymphokine
      release followed by ligand-specific unresponsiveness. Prompted by experiments
      showing that stimulation of T cells by phorbol esters in vitro results in rapid
      shedding of the L-selectin homing receptor, we investigated the expression of
      adhesion molecules on superantigen-responsive T cells in vivo. Here we show that
      bacterial superantigens cause TCR V beta-specific loss of L-selectin. Down
      regulation of L-selectin was selective, since the expression of other lymphocyte
      surface receptors was not changed. L-Selectin down-regulation represents a
      superantigen-induced immediate cell surface alteration and was not observed on T
      cells stimulated by TCR-specific antibodies. Loss of expression was almost
      complete within 30 min, and recovered 50 h after challenge. The results suggest
      that acute loss of L-selectin is a hallmark of T cell activation by bacterial
      superantigens that may result in profound changes of T lymphocyte recirculation
      pathways.

PMID- 7505016
TI  - The inhibition of different T cell lines specific for the same antigen with TCR
      antagonist peptides.
AB  - To further understand and evaluate the phenomenon of TCR antagonism, we wished to
      determine whether analogs of an antigenic determinant could antagonize a specific
      polyclonal response. To this end, the ability of TCR antagonist peptides to
      inhibit a panel of five different DR4w4-restricted, influenza hemagglutinin 307
      319-specific T cell lines was examined. An analysis of their V beta and J beta
      usage indicated that each of these five T cell lines expressed different TCR. A
      series of HA 307-319 single amino acid substituted analogs were used to determine
      the fine Ag specificities of the different lines. Ag analogs that demonstrated
      little or no stimulatory capacity were then examined for their ability to act as
      TCR antagonists by inhibiting the proliferative response of these five lines.
      Overall, 17 different peptide analogs capable of antagonizing at least one T cell
      line were identified. Although no single analog was capable of inhibiting all
      five T cell lines, two different analogs were identified that were capable of
      inhibiting four of five of the T cell specificities examined.

PMID- 7505017
TI  - Antibody specificities of Thai and Australian scleroderma sera with topoisomerase
      I recombinant fusion proteins.
AB  - Autoantibodies that react with the nuclear enzyme topoisomerase I (Topo I) are
      used as a diagnostic marker of diffuse scleroderma. To better define immune
      reactivity to Topo I, antibody epitopes in two patient populations were analyzed
      using recombinant Topo I proteins. Two overlapping partial cDNA clones encoding
      the complete amino acid sequence of Topo I were isolated from human placenta.
      Using the polymerase chain reaction, specific regions of Topo I were amplified
      and cloned into the pGEX expression vectors. To map Topo I epitopes, recombinant
      fusion proteins were analyzed by immunoblotting with 66 anti-Topo I sera from
      Thai and Australian patients with diffuse scleroderma. Six distinct epitope
      regions were identified along the length of the 765 amino acid enzyme. Almost all
      sera contained antibodies that recognized the midregion of Topo I (amino acids
      453-560), as well as antibodies to one of more of the other epitope regions.
      Sixty percent of the sera contained antibodies that recognized a COOH-terminal
      epitope region (amino acids 658-765) encompassing the active site of the enzyme.
      This subset of Topo I antibodies could be responsible for the inhibition of
      enzymatic activity previously reported in vitro. Heterogeneous patterns of
      reactivity with the six Topo I epitope regions were observed, although over half
      the sera could be assigned to one of six distinct patterns. In general,
      antibodies in the Thai sera reacted more strongly with the six epitope regions.
      Furthermore, two of the epitope regions reacted exclusively with Thai sera,
      suggesting a degree of racial or geographical specificity in the autoantibody
      response to Topo I. The identification of multiple epitopes in Topo I conforms
      with the polyclonal autoantibody response to intracellular Ag found in other
      multisystem autoimmune diseases and is presumed to be driven by the presentation
      of multiple peptides from Topo I itself.

PMID- 7505018
TI  - Peripheral human CD5+ and CD5- B cells may express somatically mutated VH5- and
      VH6-encoded IgM receptors.
AB  - Previous studies have indicated that a sizable fraction of adult human peripheral
      blood B cells may express IgM receptors encoded by somatically mutated V regions.
      From these studies it was uniquely associated with the peripheral blood B cell
      compartment, was uniquely associated with the peripheral blood B cell
      compartment, associated with particular VH gene segments and/or B cell
      subpopulations. We have addressed these issues by analyzing > 80 VH5 and VH6
      encoded mu transcripts from unseparated peripheral blood, tonsil, and spleen B
      cells, as well as from B cells separated on the basis of CD5 Ag expression. The
      results demonstrate that somatically mutated VH5 and VH6 regions are ubiquitously
      expressed in IgM-bearing B cells in all peripheral adult human lymphoid organs,
      and that the occurrence of somatic mutations does not segregate with either CD5+
      or CD5- B cell populations. The distribution and nature of mutations, as well as
      the occurrence of clonally related but divergent transcripts suggests that at
      least some of the mutations were selected by Ag.

PMID- 7505019
TI  - Substance P and somatostatin can modulate the amount of IgG2a secreted in
      response to schistosome egg antigens in murine schistosomiasis mansoni.
AB  - Substance P (SP) and somatostatin 1-14 (SOM) have immunoregulatory properties.
      Cells within the granulomas of murine schistosomiasis mansoni make both. SP
      enhances, whereas SOM inhibits soluble egg Ag (SEA)-induced, IFN-gamma
      production. IFN-gamma is important during IgG2a isotype switching. Thus, we
      investigated whether SP or SOM could affect IgG2a production in murine
      schistosomiasis. Our results show that SEA and rIFN-gamma stimulate splenic IgG2a
      secretion in murine schistosomiasis. Moreover, SP at > or = to 10(-10) M
      substantially increased both polyclonal as well as SEA-specific, IgG2a secretion
      from spleen cells challenged with SEA. However, cells exposed to SOM at > or =
      10(-10)M showed strong inhibition. Also, both SP and SOM modulated the frequency
      of IgG2a-producing cells. Splenic IgG2a production in response to SEA, SP, and
      SOM required the presence of Thy 1.2+ cells, whereas, rIFN-gamma- induced IgG2a
      synthesis did not. Also, experiments using irradiation lymphocytes showed that
      SP, SOM, or rIFN-gamma modulation of IgG2a release was not dependent on cell
      proliferation. The highly specific SP receptor antagonist, CP-96,345, completely
      inhibited the effect of SP but not SOM on IgG2a release. This suggests that SP
      acted through an authentic NK-1 receptor and that SOM required a different
      receptor interaction. Granuloma cells secreted IgG2a constitutively. Yet, neither
      SEA, SP, SOM, rIFN-gamma, nor blocking anti-IFN-gamma mAb could modulate this
      constitutive IgG2a release during short term culture conditions. Moreover, the
      IgG2a secretion also continued in the absence of Thy 1.2+ lymphocytes. However,
      mice treated with CP-96,345 or octreotide (SOM agonist) in vivo produced
      granulomas that made little or no IgG2a. Spleen cell experiments showed that SEA,
      SP, SOM, and rIFN-gamma could only affect SEA-induced, IgG2a production during
      early stages of Ag stimulation. Thus, unlike the spleen, it is probable that the
      granulomas contain mostly activated B cells that have completed switch
      recombination.

PMID- 7505020
TI  - A human monoclonal antibody specific for the N terminus of the hepatitis C virus
      nucleocapsid protein.
AB  - PBMC from a patient with chronic hepatitis C virus (HCV) infection were
      immortalized with EBV and plated by limiting dilution. Cultures secreting
      antibodies reactive in a commercial HCV II generation ELISA, which incorporates
      Ag derived from the nucleocapsid, NS3, and NS4 regions, were repeatedly cloned in
      the presence of feeder cells and growth factors. Of 23 initially immunoreactive
      cultures, only one cloned line, designated B12.F8, secreted HCV nucleoprotein
      specific IgG1(kappa), whereas no reaction with recombinant polypeptides derived
      from NS3, NS4, and NS5 regions were documented. Human mAb (hmAb) B12.F8 was shown
      to recognize the native HCV nucleoprotein expressed in eukaryotic cells
      transfected with a core cDNA construct by immunofluorescence. The fine
      specificity of this hmAb was evaluated using synthetic oligopeptides covering the
      entire HCV nucleocapsid region. A weak but consistent reactivity was observed by
      PEPSCAN using a 12-mer encompassing residues 34-45 of the HCV-deduced amino acid
      sequence. Such weak reactivity is indicative for conformational epitopes and, in
      concurrence with this assumption, we found that longer peptides from the region
      containing residues 27-59 were more efficiently recognized and effectively
      inhibited binding of hmAb B12.F8 to recombinant nucleocapsid protein. Several
      overlapping immunoreactive fragments from the nucleocapsid region were selected
      from a random cDNA library consisting of DNase I fragments of recombinant core
      Ag. Best reactive recombinants were identified within residues 1-78 of the HCV
      sequence, in agreement with the results obtained using synthetic peptides.
      Comparative experiments on the fine specificity of sera from HCV-infected
      patients with anticore antibodies invariably showed recognition of peptides 8-40
      and 27-59, as well as recombinant fragments spanning from residues 1 to 73,
      suggesting that hmAb B12.F8 identifies a major B cell epitope within the
      immunodominant nucleoprotein amino terminal subregion.

PMID- 7505021
TI  - Divergent transforming growth factor-beta effects on IL-6 regulation of acute
      phase plasma proteins in rat hepatoma cells.
AB  - The rat hepatoma cell line, H-35, responds to IL-1- and IL-6-type cytokines by an
      increased transcription of specific acute phase plasma protein (APP) genes.
      Transforming growth factor-beta (TGF-beta), although ineffective on its own in
      regulating APP genes, modulates the action of the IL-type cytokines. In growing
      cultures, the IL-6 and IL-11 stimulation of thiostatin and hemopexin is enhanced
      by TGF-beta, whereas the stimulation of other APP is reduced. The effects of
      leukemia inhibitory factor, ciliary neurotrophic factor, IL-1, and TNF-alpha are
      generally attenuated by TGF-beta. Enhancement by TGF-beta of the IL-6-induced
      response can be explained in part by the fact that TGF-beta, in combination with
      dexamethasone, stimulates severalfold the expression of the 80-kDa ligand-binding
      subunit of IL-6R. Serum deprivation of H-35 cells for 3 days leads to an enhanced
      basal and cytokine-stimulated level of APP gene expression concomitant with a
      loss of the divergent regulatory effect of TGF-beta. In growth-arrested H-35
      cells, TGF-beta still enhances the IL-6R expression but it attenuates all IL-6
      effects on APP genes. These data suggest that TGF-beta influences the signal
      transduction of the IL-type cytokines by separate mechanisms and that the
      manifestation of the TGF-beta action is modulated by the growth state of the cell
      culture.

PMID- 7505022
TI  - Regulation of integrin-mediated myeloid cell adhesion to fibronectin: influence
      of disulfide reducing agents, divalent cations and phorbol ester.
AB  - Three different agents, dithiothreitol (DTT), Mn2+, and phorbol ester (TPA), were
      found to induce HL-60 cell adhesion to fibronectin through distinct mechanisms.
      The binding of HL-60 cells to fibronectin and a 120-kDa fibronectin fragment is
      completely dependent on the alpha 5 beta 1 integrin, the adhesion activators, and
      appropriate divalent cations such as Mg2+. Mn2+ alone was able to induce maximal
      adhesion in the absence of these other activators. With any of the three
      activators, Ca2+ inhibited adhesion to fibronectin substrates by inhibiting alpha
      5 beta 1-fibronectin binding. DTT and Mn2+ were both found to enhance the binding
      of fibronectin to purified alpha 5 beta 1, which suggests that both agents can
      directly stimulate the integrin-ligand binding reaction. TPA acts by inducing
      intracellular phosphorylation whereas neither DTT nor Mn2+ induced protein
      phosphorylation. TPA-treated HL-60 cells adhere and spread on fibronectin
      substrates, whereas DTT- and Mn(2+)-treated cells adhere but do not spread. The
      actin cytoskeletal inhibitor, cytochalasin B, markedly blocks TPA-induced
      adhesion, has an intermediate effect on DTT-induced adhesion, and has a minimal
      effect on Mn(2+)-induced adhesion. Collectively, the data suggest that TPA seems
      to act by inducing phosphorylation events that lead to cytoskeletal changes and
      alpha 5 beta 1 integrin activation. In contrast, DTT and Mn2+ seem to act
      primarily by directly influencing the alpha 5 beta 1-fibronectin binding
      reaction. These studies characterize in detail a regulatory system for studying
      leukocyte alpha 5 beta 1-fibronectin adhesion and identify DTT as a novel
      activator of alpha 5 beta 1-fibronectin binding.

PMID- 7505023
TI  - Enhanced production of nitric oxide by rat alveolar macrophages after inhalation
      of a pulmonary irritant is associated with increased expression of nitric oxide
      synthase.
AB  - Alveolar macrophages represent the first line of defense of the lung against
      inhaled environmental agents. These cells release a variety of inflammatory
      mediators including reactive oxygen and nitrogen intermediates that have been
      implicated in host defense and in tissue injury. In the present studies we
      characterized production of these mediators by lung phagocytes after exposure of
      rats to an inhaled pulmonary irritant. Freshly isolated alveolar macrophages from
      control rats were found to produce nitric oxide as well as hydrogen peroxide and
      superoxide anion in response to in vitro treatment with inflammatory mediators
      such as IFN-gamma or LPS and phorbol esters, respectively. Production of nitric
      oxide by lung phagocytes was enhanced in the presence of superoxide dismutase.
      Western blot analysis revealed that production of nitric oxide after treatment of
      the cells with IFN-gamma and LPS was a result of increased expression of
      inducible nitric oxide synthase. After brief exposure of rats to ozone (O3, 1 to
      2 ppm, 3 h), a pulmonary irritant and inflammatory agent that is rapidly
      converted to molecular oxygen, lung phagocytes produced significantly increased
      amounts of nitric oxide when compared with control animals. These cells were also
      sensitized to produce more nitric oxide in response to in vitro treatment with
      IFN-gamma and LPS. This was due, at least in part, to increased expression of
      inducible nitric oxide synthase by the cells, which was evident in protein blots
      and in immunohistochemically stained sections of lung tissue. In further studies
      we found that O3 inhalation also caused enhanced production of hydrogen peroxide,
      but an apparent decrease in release of superoxide anion by lung phagocytes. Taken
      together, these data demonstrate that acute irritant exposure modifies production
      of reactive oxygen and nitrogen intermediates by lung phagocytes. These
      alterations may be important in the pathophysiologic response of the lungs to
      irritants.

PMID- 7505024
TI  - Autoantigen inhibits apoptosis of a human B cell leukemia that produces
      pathogenic rheumatoid factor.
AB  - We studied a variant CD5- B cell chronic lymphocytic leukemia (CLL) cell
      population that produces pathologic IgM kappa rheumatoid factor autoantibodies.
      In contrast to common CD5+ B cell CLL, this variant leukemia cell population
      displays intraclonal diversity in its expressed Ig V genes, similar to that noted
      for follicular B cell non-Hodgkin's lymphomas. Also, in contrast to common B cell
      CLL, these leukemia cells rapidly undergo cell death hours after being placed in
      tissue culture. We find that addition of Ag (aggregated human IgG) enhances
      significantly the survival of these cells in vitro. Leukemia cell survival also
      could be enhanced by exogenous IFN-gamma or anti-CD40 presented on Fc gamma RII
      (CDw32)-expressing L cells, but not by exogenous IL-4, IL-6, or monomeric human
      IgG. We find that Ag acts directly on the leukemia B cells to inhibit apoptosis.
      This effect could be mimicked by cross-linking the leukemia cells' surface IgM
      receptors with immobilized murine mAb specific for human Ig mu-chains, but not by
      immobilized mAb of irrelevant specificity. In contrast to most follicular NHL,
      this leukemia B cell population does not have evidence of bcl-2 gene
      rearrangement. Also, in contrast to non-Hodgkin's lymphomas and most B cell CLL,
      these cells do not express detectable amounts of bcl-2. Finally, although capable
      of inhibiting apoptosis, surface Ig receptor cross-linking does not induce
      expression of bcl-2 in these variant leukemia cells. We hypothesize that the lack
      of bcl-2 expression may render these leukemia cells particularly dependent upon
      the survival signal(s) derived from surface Ig receptor cross-linking. This state
      may represent an early stage in leukemia/lymphomagenesis, possibly accounting for
      the intraclonal diversity observed in the Ig V genes expressed by certain CD5- B
      cell leukemias and lymphomas.

PMID- 7505025
TI  - Differentiation of encephalitogenic T cells confers resistance to an inhibitory
      anti-CD4 monoclonal antibody.
AB  - The anti-CD4 mAb W3/25 inhibits experimental autoimmune encephalomyelitis (EAE)
      in Lewis rats by blocking Th cell responses to encephalitogenic determinants of
      myelin basic protein (MBP). However, it has yet to be resolved how W3/25
      modulates CD4 to inhibit EAE-associated T cell responses. This study revealed
      that W3/25 profoundly inhibited MBP-stimulated proliferation by sensitized lymph
      node cells but only partially inhibited the respective response of uncloned and
      cloned lines of MBP-specific T cells. That is, low concentrations of W3/25
      blocked 30 to 60% of MBP-stimulated proliferation, but 100-fold higher
      concentrations did not result in additional inhibition. W3/25 also inhibited MBP
      induced acquisition of EAE transfer activity, but only in cultures of freshly
      isolated lymph node cells and not in cultures of continuously propagated T cells.
      Studies focusing on the GP2.E5 T cell line revealed that the lack of sensitivity
      to W3/25 in encephalitogenic and proliferative assays was nevertheless associated
      with an effective blockage of MBP-stimulated IL-2 production. Importantly, W3/25
      specifically inhibited antigenic but not mitogenic stimulation of IL-2
      production. Reverse transcriptase/polymerase chain reaction analyses revealed
      that MBP-activated GP2.E5 T cells produced mRNA for both IL-2 and IL-4, and that
      W3/25 selectively inhibited accumulation of IL-2 as compared to IL-4 mRNA. Thus,
      GP2.E5 T cells apparently express a IL-4-dependent pathway that confers
      resistance to the inhibitory activity of W3/25. Studies focusing on two CD4+ T
      cell hybridomas revealed that W3/25 profoundly inhibited MBP-stimulated IL-2
      production but did not affect the alternative response of MBP-induced growth
      inhibition. Several other hybrids also mediated MBP-stimulated IL-2 production
      but did not express CD4 and were not affected by W3/25. These results indicate
      that: 1) interactions of W3/25 with CD4 do not necessarily block class II MHC
      restricted recognition of MBP; and 2) expression of CD4 is not necessary for Ag
      recognition by several clonotypes of MBP-reactive T cells. Rather, the results of
      this study are consistent with the concept that W3/25 inhibits transduction of
      costimulatory signals that are required specifically for initiation of IL-2
      production. These findings may have important implications for understanding the
      therapeutic potential of anti-CD4 mAb in autoimmune disease.

PMID- 7505026
TI  - Epitopes of myelin basic protein that trigger TGF-beta release after oral
      tolerization are distinct from encephalitogenic epitopes and mediate epitope
      driven bystander suppression.
AB  - We have been studying the suppression of experimental autoimmune
      encephalomyelitis in the Lewis rat after oral administration of myelin basic
      protein (MBP). Suppression is mediated by CD8+ T cells that adoptively transfer
      protection and suppress immune responses in vitro. This suppression is mediated
      by secretion of TGF-beta following triggering by the fed antigen. In the present
      study, we tested the ability of overlapping 20 amino acid peptides from MBP to
      trigger suppression mediated by spleen cells from Lewis rats orally tolerized to
      MBP. Using a transwell system, we found that spleen cells from MBP orally
      tolerized animals stimulated by residues 21-40, 51-70 and 101-120 of MBP suppress
      proliferative responses of an ovalbumin specific cell line. This suppression
      correlated with secretion of TGF-beta by cells stimulated with the peptide. In
      addition, T cells from animals fed the tolerogenic peptide 21-40 alone secreted
      TGF-beta whereas no TGF-beta release or in vitro suppression was observed in
      animals fed the MBP encephalitogenic determinant 71-90. The 71-90 peptide
      triggered proliferation of MBP primed cells from animals immunized with MBP/CFA
      whereas the suppressor epitopes identified above did not. Furthermore, oral
      administration of peptide 21-40 suppressed disease induced by peptide 71-90. DTH
      responses to 71-90 were not affected by oral administration of peptide 21-40
      whereas DTH responses to whole MBP were suppressed. These results demonstrate
      that distinct suppressor determinants exist on MBP which are separate from
      encephalitogenic determinants, and that epitope-driven bystander suppression
      plays an important role in down-regulation of tissue specific autoimmune
      processes following oral tolerization. These findings have important implications
      for the design of tissue specific targeted immunotherapy by oral tolerization in
      humans.

PMID- 7505027
TI  - Conventional B cells, not B1 cells, are the source of autoantibodies in chronic
      graft-versus-host disease.
AB  - B1 (CD5+) B cells have been implicated as a source of certain autoantibodies in
      several murine and human studies. We have previously shown in the lpr model of
      autoimmunity, however, that conventional B cells, not B1 cells, were the source
      of autoantibodies directed at chromatin, ssDNA, and IgG. In the current study, we
      have investigated the origin of autoantibodies in chronic graft-versus-host (GVH)
      disease, induced in nonautoimmune mice by transferring la-incompatible spleen
      cells. GVH mice develop multiple autoantibodies and significant kidney damage.
      Therefore, this model allowed us to examine the B cell subset involved in both
      autoantibody production and tissue injury. We used two protocols to establish B
      cell chimeras that possessed immunoglobulin heavy chain (lgh) allotype-marked
      peritoneal (B1-cell source) cells and bone marrow-derived (conventional B cell
      source) cells from nonautoimmune C57BL/6kh (B6) congenic mice. In both types of
      chimera, chronic GVH was induced by giving mice alloreactive T cells i.p. All of
      the subsequent anti-chromatin, RF, and anti-ssDNA autoantibodies were produced by
      the conventional B cells and not by B1 cells. In addition, glomerular immune
      complex deposits of both IgM and IgG originated from the conventional B cells and
      not from B1 cells. These findings thus parallel those from our previous work on
      autoantibodies in lpr, and extend those findings by demonstrating that antibodies
      within pathogenic immune complexes in the kidneys are also exclusively of
      conventional B cell origin.

PMID- 7505028
TI  - [Effect of rG-CSF on the morphology and function of neutrophils in ovarian cancer
      chemotherapy].
AB  - The combined use of rG-CSF in ovarian cancer chemotherapy prevents a decrease in
      the number of neutrophils and promotes their recovery. rG-CSF also protects
      against infections, enhancing chemotherapeutic effectiveness. It is reported that
      neutrophils produced by rG-CSF not only increase in number but also in function.
      Some clinicians, however, doubt whether neutrophils mobilized or produced by rG
      CSF have sufficient ability to function practically in clinical cases. We
      therefore examined, by means of flow cytometry, the neutrophils' phagocytosis and
      bactericidal ability and we found both normal. No morphological abnormalities
      were seen in these neutrophils. In our observations, moreover, no effect was
      exerted on the leukocyte-membrane antigen. It was concluded that (a) rG-CSF was
      very effective in protecting against the diminution of neutrophils by
      chemotherapy and (b) in promoting their recovery, and (c) also the function,
      morphology and leukocyte-membrane antigen of these neutrophils were normal.

PMID- 7505029
TI  - [A case of acute myeloblastic leukemia invaded uterine cervix-diagnosed by
      changes in peripheral blood after G-CSF administration].

PMID- 7505030
TI  - The regulation of osteoblast function by hormones and cytokines with special
      reference to insulin-like growth factors and their binding proteins.

PMID- 7505031
TI  - Role of insulin-like growth factor (IGF) II and IGF binding proteins in
      extrapancreatic tumour hypoglycaemia.

PMID- 7505032
TI  - Toxicity of polyoxyethylene hydrogenated castor oil 60 (HCO-60) in experimental
      animals.
AB  - HCO-60, a polyoxyethylene castor oil derivative, is used as a solubilizer in the
      injectable formulations of lipophilic agents. This study was performed to examine
      the toxicity of HCO-60 in various experimental animals including dogs, monkeys,
      rabbits, guinea pigs and rats. With 1.25 or 2.5 mg/kg of HCO-60 injected i.v. to
      dogs, blood pressure decreased, flush, swelling and itching appeared after
      injection, and with 10 mg/kg of HCO-60 there was additionally a decrease of
      spontaneous motility. In the two higher dose groups, these symptoms paralleled an
      increase of histamine levels. Since degranulation was observed after injection in
      the mast cells of the skin, but not in the liver of dogs, the histamine in the
      plasma was considered to be released from the mast cells of the skin.
      Pretreatment with diphenhydramine, a H1-receptor antagonist, suppressed the
      decrease of blood pressure induced by HCO-60. These findings show that the
      toxicity of HCO-60 is associated with histamine release from the mast cells. No
      symptoms occurred in monkeys, rabbits, guinea pigs or rats with 50 or 100 mg/kg
      of i.v. of HCO-60, and there was no change in plasma histamine levels. This study
      demonstrated that the toxicity of HCO-60 is species specific to dogs among the
      animals tested.

PMID- 7505033
TI  - Effect of the new calcium antagonist (+/-)-(R*)-3-[(R*)-1-benzyl-3- piperidyl]
      methyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5- pyridinedicarboxylate
      hydrochloride (KW-3049) on cardiac hypertrophy in spontaneously hypertensive
      rats.
AB  - Using spontaneously hypertensive rats (SHR), we studied the effects of a new
      calcium antagonist, (+/-)-(R*)-3-[(R*)-1-benzyl-3-piperidyl] methyl 1,4-dihydro
      2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate hydrochloride (KW-3049)
      on the development of hypertension and cardiac hypertrophy. When KW-3049 was
      administered orally to 5-week-old SHR, a stage before the onset of hypertension,
      for 12 consecutive weeks, it showed a dose-dependent and marked antihypertensive
      action. Administration of 3 mg/kg of KW-3049, once a day, significantly
      suppressed the rise in blood pressure to a similar extent to 15 mg/kg of
      nicardipine, twice a day. After 12 weeks of administration, the heart weight was
      decreased or tended to be decreased. Co-administration with propranolol markedly
      decreased the heart rate, but little affected the heart weight, suggesting
      changes in the heart rate during the long-term administration of KW-3049 did not
      largely affect cardiac hypertrophy. KW-3049 did not increase plasma renin
      activity (PRA) or plasma aldosterone concentration (PAC). There was no
      significant change in the myocardial DNA and RNA contents. These results suggest
      the clinical usefulness of KW-3049 as an antihypertensive drug.

PMID- 7505034
TI  - Assisted suicide: sheer cliff or clinical reality?

PMID- 7505035
TI  - [Study of cell lines derived from benign hypertrophic prostate tissue].
AB  - Primary epithelial and fibroblast cells from benign hypertrophic prostate tissue
      were established. The prostate tissues were obtained by transurethral resection
      of the prostate or retropubic prostatectomy in patients with benign prostatic
      hypertrophy. Growth factors for cultured epithelial cells and fibroblasts were
      studied. The epithelial cells grew well in the WAJC-404 culture medium with
      insulin, epidermal growth factor and dexamethasone. Fibroblasts grew well in
      culture medium containing 10% fetal calf serum. The prostate tissue was stored at
      4 degrees C for 7 days and no degenerative change in the stromal cells was seen
      during this period. Although epithelial cells did degenerate with the passage of
      time, epithelial cells cultured after storage for 4 days at 4 degrees C behaved
      similarly to those cultured immediately after being isolated. These primary
      cultures of epithelial cells and fibroblasts from hypertrophic prostate may be
      useful for various studies.

PMID- 7505036
TI  - Platelet involvement in experimental immune complex-mediated glomerulonephritis
      in the nonhuman primate.
AB  - Abundant glomerular platelet deposition is a hallmark of certain animal models of
      immune complex (IC)-mediated glomerulonephritis (GN). By contrast, conspicuous
      platelet deposition is uncommon in the IC-GN seen in humans. This could result
      from intrinsic differences between human and animal platelets, which are known to
      be present. To assess whether abundant glomerular platelet deposition can occur
      in humans with IC-GN, the present studies were undertaken in nonhuman primates
      (cynomolgus monkeys, CYN), with active experimental IC-GN induced by 12 weeks of
      daily intravenous infusion of bovine gamma globulin (BGG). CYN are appropriate
      for these studies because, like humans, CYN platelets do not express the C3b
      receptor but do express receptors for the Fc region of IgG (FcR gamma II).
      Furthermore, in this model of IC-GN, which is indistinguishable from IC-GN seen
      in humans, it is possible to time the biopsy to coincide with a period of peak
      activity of the GN. The present studies proceeded as follows: ten CYN were
      studied before and after intravenous infusion of BGG sufficient to achieve
      conditions near antigen/antibody equivalence for circulating precipitating
      antibody to BGG. The infusion of BGG, which was given over 10 minutes, resulted
      in an acute reduction in circulating platelets (mean 43% +/- 5 SE, P < 0.001).
      However, renal biopsies performed before and five minutes after the acute
      reduction in circulating platelets showed that relatively few of the platelets
      removed from the circulation lodged in glomeruli (platelets/glomerular cross
      section: 0.2 +/- 0.06 before BGG vs. 0.88 +/- 0.31 after BGG, P = 0.035). In five
      of the CYN studied under the above protocol, autologous platelets were labeled
      with 111In and reinfused into the CYN just prior to the BGG infusion. These
      studies confirmed the paucity of platelet deposition in kidney but showed major
      uptake of the 111In-labeled platelets by liver and spleen (mean +/- SE 111In
      CPM/mg of tissue: kidney cortex 18 +/- 8, liver 132 +/- 42, and spleen 808 +/-
      127, P = 0.038, comparing kidney to liver or spleen by paired t-test). Thus, the
      platelets removed from the circulation were taken up at the sites which are also
      the principal sites of IC uptake (liver and spleen), and over the time interval
      that coincides with the period of maximum uptake of IC by liver and spleen, after
      BGG infusion. In vitro studies, discussed herein, showed that BGG anti-BGG IC
      bind to CYN platelets via FcR gamma II.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7505037
TI  - TNF alpha induces expression of the chemoattractant cytokine RANTES in cultured
      mouse mesangial cells.
AB  - We investigated the effect of several immune-relevant cytokines on expression of
      the chemoattractant intercrine/chemokine RANTES in a mouse mesangial cell line
      (MMC). Fifty ng/ml recombinant tumor necrosis factor alpha (TNF alpha) induced a
      marked increase in RANTES transcripts after two hours. RANTES mRNA remained
      elevated for 24 to 48 hours after stimulation, and could be abolished by co
      incubation with 30 micrograms/ml of a neutralizing rabbit anti-TNF alpha
      antibody. Protein expression of RANTES, as assessed by indirect
      immunofluorescence and Western blotting, increased in MMCs 24 hours after TNF
      alpha stimulation. Interleukin-1 beta, tumor necrosis factor beta (TNF beta), and
      lipopolysaccharide (LPS) also increased expression of RANTES mRNA. In addition,
      RANTES mRNA expression was stimulated in glomeruli harvested from rats following
      renal in vivo perfusion with TNF alpha. Our results indicate that mesangial cells
      produce the small cytokine RANTES. This factor, in concert with other
      chemoattractants, may play a role in the glomerular recruitment of inflammatory
      cells like macrophages/monocytes.

PMID- 7505038
TI  - Expression of vascular cell adhesion molecule-1 in kidney allograft rejection.
AB  - VCAM-1, a leukocyte adhesion molecule expressed by cytokine-activated endothelial
      cells in culture, may mediate mononuclear leukocyte infiltration in vessels and
      interstitium in solid organ allograft rejection. Using the avidin-biotin
      immunoperoxidase technique and an affinity-purified rabbit polyclonal antisera to
      recombinant human VCAM (rVCAM Ab) which works in methyl Carnoy's fixed tissues,
      we studied the expression of this molecule in biopsies of transplanted kidneys (N
      = 34) with and without features of rejection and allograft nephrectomies (N = 17)
      as well as nontransplanted control tissues (N = 26). The rVCAM Ab showed a
      population of reactive endothelial cells limited to sites of prominent
      subendothelial leukocytic cell infiltration in arteries and veins, and occasional
      peritubular capillaries (PTC) in rejecting allografts. Endothelial expression of
      VCAM was rarely identified in biopsies showing interstitial rejection only or
      cyclosporine toxicity, usually in PTC, and was only rarely encountered in
      nontransplanted control tissues. Apparent de novo expression of VCAM-1 by
      arterial smooth muscle cells and mesangial cells was present in cases of severe
      rejection. In addition, a population of cells (DC) with dendritic morphology was
      identified by rVCAM Ab within sites of lymphoid cell aggregation in rejecting
      allografts. Further evidence that these cells represent true DC was obtained by
      identification of VCAM-1 positive, morphologically similar cells in both germinal
      centers and interfollicular areas of all seven reactive lymph nodes tested; and
      by similar staining of these cells in the allografts and lymph nodes by
      antibodies to nerve growth factor receptor and the complement receptor CR1,
      previously shown to recognize DC. DCs were generally not seen in uninflamed
      normal control organs or portions of allografts uninvolved by lymphoid
      aggregates. Enhanced tubular epithelial cell expression of VCAM-1 was also
      present in rejecting allografts. All staining could be abolished by absorption of
      the antisera with VCAM-1 transfected, but not ICAM-1 or ELAM-1 transfected, CHO
      cells. In situ hybridization studies utilizing a cDNA probe to human VCAM-1
      demonstrated mRNA production by glomerular, tubular and vascular cells
      corresponding to sites where the protein was immunohistochemically
      localized.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7505039
TI  - Immunohistochemical distribution and quantification of crystal matrix protein.
AB  - The aim of this study was to determine the immunohistochemical distribution and
      quantification of crystal matrix protein (CMP). CMP, a 31 kDa glycoprotein, is
      the principal macromolecule found in calcium oxalate crystals generated in human
      urine, and is a potent inhibitor of crystal aggregation. A polyclonal rabbit anti
      human CMP antibody was used to examine renal tissue by immunohistochemical
      techniques and light microscopy (N = 45). Twenty-five other human organs were
      similarly assessed. Quantification was performed using a visual analogue scale.
      CMP was visible as cytoplasmic staining in the epithelial cells of the TALH and
      the distal convoluted tubule including the macula densa in a subgroup of
      nephrons. CMP was not identified elsewhere in the urinary tract or in the
      extrarenal organs examined. Despite a trend indicating that the kidneys of normal
      men had more CMP than those of normal women, the difference failed to reach
      significance (P = 0.11). There was, however, more CMP in the stone formers group
      compared with either normal men (P < 0.01) or normal women (P < 0.01). This
      protein may be an important determinant of calcium oxalate kidney stone disease.

PMID- 7505040
TI  - Diagnostic value of bone marrow biopsy in patients with renal disease secondary
      to familial Mediterranean fever.
AB  - Systemic AA type amyloidosis with renal involvement is the major cause of
      morbidity and mortality in patients with familial Mediterranean fever (FMF). A
      histopathological examination is essential to achieve a definite diagnosis in
      systemic amyloidosis. The diagnostic yield of the procedure varies according to
      the biopsy site and renal biopsy has the highest yield. On the other hand this
      procedure has its own complications and requires hospitalization of the patient.
      Alternative biopsy sites have been proposed with varying degrees of sensitivity
      and morbidity to reduce the morbidity and mortality of solid organ biopsies. We
      performed bone marrow biopsies in 39 patients with FMF who had different stages
      of renal disease. Thirty-one (79.5%) of the 39 specimens showed significant
      perivascular amyloid infiltration when stained with crystal violet and Congo red.
      An immunoperoxidase stain with a monoclonal antibody proved that these deposits
      were AA type amyloid. We suggest that bone marrow biopsy can be utilized for a
      safe and quick diagnosis of systemic amyloidosis in patients with FMF and renal
      disease.

PMID- 7505041
TI  - Interferon treatment of human malignancies--a short review.
AB  - Interferon (IFN) therapy can induce remissions in human malignancies and has been
      established as a treatment of choice in several diseases. The clinical effects of
      IFNs are especially obvious in the treatment of hematological malignancies and
      virus-associated tumor diseases. Most other types of malignant solid tumors are
      less likely to respond to IFN as monotherapy and optimal therapeutic schedules
      are yet to be developed. It is of special interest that combinations of IFNs with
      other treatment modalities have yielded an increased response rate in several
      diseases. Several studies on the use of IFN as adjuvant therapy are under way. It
      is possible, if not likely, that the antitumor effects of IFNs are mediated by
      different cellular effects in cooperation. These may differ between different
      malignancies. Mainly based on studies comparing in vitro sensitivity of malignant
      cells to clinical effects on the same tumor, we suggest that the direct effects
      of IFNs on the malignant cell are of major importance for the antitumor action of
      IFN. A deepened insight into the cellular aspects of the antitumor action of
      these cytokines is a prerequisite for the optimal use of IFNs in the treatment of
      tumors in man.

PMID- 7505042
TI  - Interleukin-2 and interferon in renal cell carcinoma.
AB  - Renal cell cancer (RCC) represents an unusual solid tumor for which no treatment
      other than surgical therapy has been effective. This tumor demonstrates a
      remarkably heterogeneous behaviour and rare reports of spontaneous regressions
      suggest an unusual sensitivity to host immunologic control. In recent years the
      rapid development in molecular genetics, growth factors and cytokine--lymphocyte
      interactions have increased the interest and possibilities for immunotherapy of
      RCC. Interleukin-2 (IL-2) or Interferon alpha (IFN alpha) alone are only
      marginally active in RCC. Their different modes of action and their synergistic
      effects when used in experimental murine models prompted the investigation of
      combined IL-2/INF alpha therapy in advanced RCC. The advantage of a combination
      of IL-2 and IFN alpha treatment as compared to LAK cell treatment seems to be
      that IL-2 and IFN alpha can be given at lower dosages without compromising the
      results in an outpatient setting. This article reviews the use of IL-2 and IFN
      alpha in combination for treatment of RCC and discusses the current problems and
      future challenges in this field.

PMID- 7505043
TI  - Reflections on human tumor immunology.

PMID- 7505044
TI  - Outcome of acute symptomatic non-A, non-B hepatitis: a 13-year follow-up study of
      hepatitis C virus markers.
AB  - Thirty-nine of 61 prospectively followed patients who had had acute non-A, non-B
      hepatitis in 1978 were clinically reexamined in 1991 and tested for antibodies to
      hepatitis C virus (anti-HCV) with a second generation ELISA and RIBA and for HCV
      RNA by PCR. Acute hepatitis C was diagnosed in stored sera from 1978 in 24
      patients, who were found still to be anti-HCV positive in 1991, and 16 of them
      were also HCV RNA positive. The majority of anti-HCV positive patients with or
      without HCV RNA had elevated serum ALT levels 13 years after onset of their acute
      hepatitis C. After 13 years follow-up, 1.6% of the patients had died of end-stage
      liver disease, 8% of anti-HCV positive patients had histologically confirmed
      liver cirrhosis, 79% of anti-HCV positive patients were judged to have chronic
      infection, whereas 21% seemed to have recovered. To conclude, we found that a
      majority of our patients with acute symptomatic hepatitis C continued to be
      viraemic 13 years after onset of hepatitis C, and that all continued to be anti
      HCV positive by second-generation ELISA.

PMID- 7505045
TI  - The role of ultrasound in prostate cancer detection in patients with an elevated
      prostate specific antigen level but no prostatic nodule.
AB  - An increased level of prostate specific antigen (PSA) in the blood is a
      relatively sensitive indicator of prostate disease; a significant minority of men
      with increased PSA will have prostate carcinoma. A total of 736 men with a PSA
      elevation of greater than 4.2 without a rectally palpable prostate mass were
      evaluated with transrectal ultrasound at the Ultrasound Institute of Baltimore
      over a three-year period. Transrectal biopsy under ultrasound control was
      performed when a localized mass was seen on ultrasound or the prostate was small
      and the PSA level significantly elevated (93% of the series underwent biopsy).
      There was a positive biopsy yield for cancer of 38.5% in the cases biopsied. This
      high positive yield was achieved by combining high quality ultrasound with two to
      three samples from a visible mass and random samples from other sites.

PMID- 7505046
TI  - Pathogenesis of diabetic retinopathy--the missing link?
AB  - Release of angiogenic factors in response to the ischaemic retina is currently
      the most favoured hypothesis for the pathogenesis of proliferative diabetic
      retinopathy. Reducing the stimulus for angiogenesis by destroying the ischaemic
      retina also forms the basis of the most effective treatment of diabetic
      retinopathy by photocoagulation. Though ischaemia is undoubtedly important for
      neovascularization, there is recent evidence which cast doubts on ischemia being
      the sole mechanism for diabetic retinopathy. Many clinical observations viz. the
      protective effects of glaucoma, myopia, unilateral carotid stenosis on diabetic
      retinopathy; and its worsening after cataract extraction are not adequately
      explained by the present hypothesis. Moreover, the recent in vitro culture
      studies on retinal pigment epithelial cells have suggested an alternative
      explanation for the effectiveness of photocoagulation in proliferative diabetic
      retinopathy. Furthermore, hyperglycemia has been strongly correlated with the
      incidence and progression of diabetic retinopathy, but has only been indirectly
      indicted in its pathogenesis. These facts can be integrated into a more plausible
      hypothesis for the pathogenesis of diabetic retinopathy. It is hypothesized that
      a relative reduction in intra-ocular pressure caused by persistent or
      intermittent hyperglycemia may be the missing link that induces certain
      morphological changes in the retinal pigment epithelium. These changes, in
      addition to the ischaemic retina, may be important for the pathogenesis of
      diabetic retinopathy. Such a hypothesis also explains most of the hitherto
      unexplained features of diabetic retinopathy.

PMID- 7505047
TI  - Management of pineal non-germinoma germ cell tumor with residual teratoma and
      normal alpha-fetoprotein.
AB  - A 16-year-old white male presented with multiple abnormal extraocular movements
      secondary to an enhancing pineal tumor. Subtotal resection of the lesion revealed
      a mixed malignant germ cell tumor. The preoperative serum alpha-fetoprotein (AFP)
      was markedly elevated at 155 IU/L. The patient subsequently received radiotherapy
      and adjuvant chemotherapy consisting of cisplatin rotating monthly with
      vincristine and cyclophosphamide, with dramatic tumor regression and return of
      AFP to normal. Eighteen months later the persistence of a substantial tumor mass
      despite a normal AFP raised concern for residual active tumor. Histological
      examination of the resected lesion revealed benign teratoma and fibrous tissue.
      Repeat management of mixed malignant germ cell tumors, which demonstrate a
      persistent mass following an initial response to treatment.

PMID- 7505048
TI  - Ifosfamide-induced renal tubular defect.
AB  - We describe 2 cases of proximal tubular defects induced by the administration of
      ifosfamide at a dosage of 6 g/m2/course over 2 days in children with a diagnosis
      of malignant mesenchymal tumors. This adverse effect could be minimized dividing
      dosage of the drug. However at present it is not clear if divided doses are
      completely safe.

PMID- 7505049
TI  - Hepatocellular carcinoma in the very elderly: to treat or not to treat?
AB  - We report a case of a patient with hepatocellular carcinoma (HCC) who has two
      unusual features. The patient was 95 years old at the time of diagnosis and his
      excellent response to treatment. The authors briefly review the age distribution
      of HCC and the treatments used. We concluded that therapy should not be
      arbitrarily withheld based solely on chronological age. Older cancer patients
      deserve the right to be treated if they so wish.

PMID- 7505050
TI  - Intraabdominal desmoplastic small-cell tumor with divergent differentiation:
      clinicopathological findings and DNA ploidy.
AB  - Five cases of intraabdominal small-cell tumor with divergent differentiation are
      reported. All patients were of male sex. They were 10, 15, 20, 21, and 30 years
      of age at time of diagnosis, respectively. By light microscopy, the tumors
      consisted of small cells arranged in groups, nests, and clusters separated by a
      collagen-rich desmoplastic stroma. Immunohistochemical studies revealed the
      coexpression of mesenchymal, epithelial, and neural markers. Notably, all tumors
      coexpressed vimentin, cytokeratin, and desmin, the latter in a remarkable
      paranuclear dot-like fashion. In contrast to other authors, we did not find
      chromogranin. DNA image cytometry on four cases demonstrated two diploid and two
      aneuploid (hyperdiploid) cases. No correlation was found between ploidy and
      prognosis. One patient died from disease, another died from veno-occlusive
      disease after bone marrow transplantation, and the remaining patients are alive,
      but have progressive intraabdominal disease. Thus, our findings support the poor
      prognosis in this type of tumor.

PMID- 7505051
TI  - Finasteride.

PMID- 7505052
TI  - Cell adhesion. Mucins in the mainstream.

PMID- 7505053
TI  - L-selectin-mediated lymphocyte rolling on MAdCAM-1.
AB  - The L-selectin, a cell surface C-type lectin, directs lymphocyte traffic to lymph
      nodes, and contributes to lymphocyte homing to Peyer's patches and to leukocyte
      interactions with inflamed venules. Here we report that the mucosal vascular
      addressin MAdCAM-1, a mucosal endothelial adhesion molecule with immunoglobulin-
      and mucin-like domains, is a facultative ligand for L-selectin. MAdCAM-1 isolated
      from mesenteric lymph nodes, but not from cultured endothelioma cells, bears N
      glycanase-resistant sialic acid-containing carbohydrate which supports adhesion
      of L-selectin-transfected lymphoid cells under shear. Interacting lymphoid cells
      display a 'rolling' behaviour similar to the selectin-dependent rolling of
      neutrophils observed in inflamed venules. MAdCAM-1 is also a ligand for the
      lymphocyte integrin homing receptor for Peyer's patches, alpha 4 beta 7 (ref. 7),
      and may be uniquely adapted to support both selectin-mediated lymphocyte rolling
      and integrin-mediated adhesion and arrest in vivo.

PMID- 7505054
TI  - Heterogeneity of type I collagen expression in human corneal keratoconus
      fibroblasts.
AB  - Corneal fibroblast cultures were established from 3 normal and 4 keratoconus (KC)
      corneas. Type I collagen protein synthesis and steady-state RNAs were analyzed in
      these cultures by metabolic labeling studies, slot blots and immunofluorescent
      microscopy. Type I collagen proteins and steady-state RNAs were reduced in cells
      from 3 of the 4 KC cultures when compared with normal fibroblasts, suggesting
      that collagen expression is heterogenous in KC and that the heterogeneity is
      expressed at the cellular and molecular level. The type I collagen matrix
      synthesized by the KC fibroblasts appeared normal when analyzed by
      immunofluorescence, suggesting that the incorporation of type I collagen into the
      extracellular matrix is not affected in KC fibroblasts.

PMID- 7505055
TI  - [Results of the treatment of inoperable recurrences of larynx carcinoma after
      total laryngectomy].
AB  - Since 1975 to 1989 in the Department of Radiotherapy of Centre of Oncology in
      Krakow 49 patients with inoperable recurrences of the larynx carcinoma after
      total laryngectomy were treated. The palliative therapy (chemotherapy and/or
      palliative radiotherapy) was used in 18 patients. This study presents the group
      of 31 patients which were treated with radical intent. Radical radiotherapy was
      used in 20 patients. Combined multidrug chemotherapy and radiotherapy was used in
      11 patients: in 2 patients chemotherapy VBM was used in combination with
      radiotherapy and 9 patients received the induction chemotherapy (treatment
      schedules containing Cisplatin) followed by radical radiotherapy. Observations
      show that the effectiveness of the induction chemotherapy combined with
      radiotherapy. Two year symptom-free 3 patients (15). Better results were observed
      after combined treatment with the use the induction chemotherapy combined with
      radiotherapy. Two year symptom-free survival was achieved in 4 patients (44%).
      These findings require confirmation in the greater group of patients.

PMID- 7505056
TI  - Expression of NEU/HER-2 oncoprotein (p185neu) in prostate tumors: an
      immunohistochemical study.
AB  - The expression of the neu oncogene product was investigated immunohistochemically
      in 36 cases of benign prostatic hyperplasia (BPH) and seven cases of
      adenocarcinoma of prostate (CaP). c-neu oncogene encodes a transmembrane growth
      factor receptor that has partial structural homology with EGF receptor, and is
      overexpressed and amplified in a number of human tumors, specially, breast
      cancers. Using a monoclonal antibody, AB-3, which recognizes -COOH-terminal of
      neu oncoprotein, we have analyzed immunohistochemically the expression of this
      protein in buffered formalin and Zamboni fluid-fixed surgically removed tissues.
      Focal patchy and/or diffused cytoplasmic staining of varying intensity was
      observed in 34 of 36 BPH cases. Four cases showed cell membrane staining as well
      (4/36 = 11%). All seven cases of adenocarcinomas had moderate to strong c-neu
      immunoreactivity, and two gave a distinct cell membrane-positive reaction (100%).
      The available data indicate that prostatic tumors as well as a high percentage of
      prostatic hyperplasia tissues express c-neu protein; however, its role in
      cellular proliferation needs further study.

PMID- 7505057
TI  - Purification of human blood basophils and leukotriene C4 generation following
      calcium ionophore stimulation.
AB  - A simple method for purification of basophils from a relatively small volume of
      blood has been developed, which enables us to collect basophils with a purity of
      over 80%. Basophils were partially purified from 10-20 ml of citrated whole blood
      using the discontinuous Percoll density gradient centrifugation technique and
      then contaminant cells were removed using monoclonal antibodies against CD2,
      CD19, CD14 and CD16. At the end of the procedure, basophils were > 80% pure with
      lymphocytes accounting for most of the contaminating cells. When stimulated with
      anti-IgE or fMLP, histamine release from purified basophils was similar to that
      from mixed leukocytes. When highly purified basophils were challenged with
      calcium ionophore A23187, generation of leukotriene C4 (LTC4) was not
      significantly different between asthmatic patients and normal subjects (45.6 +/-
      22.6 vs 52.7 +/- 25.6 ng/10(6) cells). Basophils were capable of generating LTC4
      in approximately the same quantities as eosinophils (46.5 +/- 11.7 ng/10(6)
      cells, n = 3). Furthermore, it has been shown that incubation of basophils and
      eosinophils with calcium ionophore generates only small quantities of thromboxane
      B2 (TXB2).

PMID- 7505058
TI  - Prostaglandin D2 and endothelin-1 induce the production of prostaglandin F2
      alpha, 9 alpha, 11 beta-prostaglandin F2, prostaglandin E2, and thromboxane in
      capillary endothelium of human brain.
AB  - Endothelial cells derived from human brain capillaries (HBCEC) synthesize
      prostaglandin D2 (PGD2) which can be stimulated, among other prostanoids, by
      endothelin 1 (ET-1). Both the PGD2 induced by ET-1 and the exogenously added PGD2
      to HBCEC are converted to 9 alpha, 11 beta-prostaglandin F2 (9 alpha, 11 beta
      PGF2), a known potent vasoconstrictor. Exogenous PGD2 also dose-dependently
      enhanced the production of vasoconstrictive PGF2 alpha, thromboxane B2 (TXB2),
      and the vasodilatory PGE2 as well as cAMP by HBCEC. The PGD2-induced formation of
      PGF2 alpha, PGE2, and TXB2 was reduced by the cyclooxygenase inhibitors
      acetylsalicylic acid (ASA) or indomethacin (Indo), indicating for the first time
      that PGD2 may contribute to the formation of prostanoids in HBCEC. These results
      strongly suggest that PGD2 may play an important role in the regulation of
      cerebral capillary function under physiologic and pathologic conditions.

PMID- 7505059
TI  - Lead in the ambient air and blood specimens of children in Helsinki.
AB  - Ambient air lead concentrations have been measured in Helsinki since 1978. The
      mean concentrations at various stations reached maximum values in 1980, being
      then 209-1150 ng/m3. From 1980 to 1991 the concentrations decreased to one-eighth
      (335-41 ng/m3) at the three stations where measurements were made continuously.
      Concomitantly the estimated annual lead emissions in Helsinki decreased from 78
      to 9 tons, mainly owing to the reduced emissions of lead in exhaust gases from
      road traffic. The mean concentration of lead in the blood of children in day-care
      centres was 46 micrograms/l in 1983 and 30 micrograms/l 5 years later. Similar
      concentrations were found in blood samples from a day-care centre beside a street
      with heavy traffic and in those from an area with less traffic.

PMID- 7505060
TI  - Can DNA mimics improve on the real thing?

PMID- 7505061
TI  - Translocation of repetitive RNA sequences with the germ plasm in Xenopus oocytes.
AB  - Xlsirts are a family of interspersed repeat RNAs from Xenopus laevis that contain
      from 3 to 13 repeat units (each 79 to 81 nucleotides long) flanked by unique
      sequences. They are homologous to the mammalian Xist gene that is involved in X
      chromosome inactivation. Xlsirt RNA appears first in the mitochondrial cloud
      (Balbiani body) in stage 2 oocytes and is then translocated as island-like
      structures to the vegetal cortex at early stage 3 coincident with the
      localization of the germ plasm. Exogenous Xlsirt RNA injected into oocytes
      translocates to the location of the endogenous RNA at that particular stage. The
      Xlsirt RNA repeat sequences are required for translocation and can cause the
      translocation of heterologous unique RNAs to the vegetal cortex.

PMID- 7505062
TI  - Abnormal chromosome behavior in Neurospora mutants defective in DNA methylation.
AB  - The function and regulation of DNA methylation in eukaryotes remain unclear.
      Genes affecting methylation were identified in the fungus Neurospora crassa. A
      mutation in one gene, dim-2, resulted in the loss of all detectable DNA
      methylation. Abnormal segregation of the methylation defects in crosses led to
      the discovery that the methylation mutants frequently generate strains with extra
      chromosomes or chromosomal parts. Starvation for S-adenosylmethionine, the
      presumed methyl group donor for DNA methylation, also produced aneuploidy. These
      results suggest that DNA methylation plays a role in the normal control of
      chromosome behavior.

PMID- 7505063
TI  - 5-HT3 receptors which modulate [3H]5-HT release in the guinea pig hypothalamus
      are not autoreceptors.
AB  - The 5-HT3 agonist 2-methyl-5-HT had previously been shown to enhance the
      electrically evoked release of [3H]5-HT from preloaded slices of the guinea pig
      brain. In the present study, 2-methyl-5-HT (1 microM) was also found to increase
      the K+ evoked release of [3H]5-HT from preloaded slices of the guinea pig
      hypothalamus and this effect was blocked by the selective 5-HT3 antagonist
      ondansetron. In the presence of tetrodotoxin, the enhancement of the K(+)-evoked
      release of [3H]5-HT by 2-methyl-5-HT in hypothalamus slices was blocked, thus
      suggesting that the 5-HT3 receptors mediating this effect are not located
      directly on 5-HT terminals. In agreement with this, 2-methyl-5-HT did not alter
      the K(+)-evoked release of [3H]5-HT in a synaptosomal preparation of the same
      brain structure, even at a concentration 10-fold greater than that used in the
      slices. Taken together, these data indicate that these facilitatory 5-HT3
      receptors are not located on 5-HT terminals in the guinea pig hypothalamus and
      therefore are not autoreceptors.

PMID- 7505064
TI  - Cloning of the cDNA encoding human platelet CD36: comparison to PCR amplified
      fragments of monocyte, endothelial and HEL cells.
AB  - Glycoprotein CD36, also known as GPIIIb or GPIV, is a major platelet glycoprotein
      that bears the newly identified Naka alloantigen. The aim of this study was to
      clone platelet CD36 and investigate other forms of CD36-cDNA present in
      monocytes, endothelial and HEL cells. RNA from above mentioned cells were reverse
      transcribed (RT), using specific primers for CD36, and amplified by the
      polymerase chain reaction (PCR) technique. Sequencing the different amplified
      platelet derived cDNA fragments, spanning the whole coding and flanking regions,
      showed the near identity between platelet and CD36-placenta cDNA. Platelet CD36
      cDNA cross-hybridized, in Southern blots, with RT-PCR amplified cDNA originating
      from monocytes, endothelial and HEL cells. However, monocytes showed a RT-PCR
      amplified cDNA fragment (561 bp) that was present in platelets and placenta but
      not on endothelial on HEL-cells. Northern blot analysis of platelet RNA
      hybridized with placenta CD36 indicated the presence of a major (1.95 kb) and a
      minor (0.95 kb) transcript. The 1.95 kb transcript was the only one observed on
      Northern blots of monocytes, endothelial and HEL cells. These results indicate
      that the structure of CD36 expressed in platelets is similar, with the exception
      of the 3' flanking region, to that of placenta. Differences in apparent molecular
      weight between CD36 and CD36-like glycoproteins may be due to post-translational
      modifications.

PMID- 7505065
TI  - The platelet glycoprotein IIb/IIIa complex is involved in the adhesion of
      activated platelets to leukocytes.
AB  - The adhesion of activated platelets to leukocytes (rosette formation) seems to be
      mediated by CD62 on platelets and its counter-receptor (CD15 or a sialic acid
      containing glycoprotein) on polymorphonuclear leukocytes (PMNL). However, neither
      treatment of platelets with an anti-CD62 antibody or fucoidan nor treatment of
      PMNL with anti-CD15 antibody or neuraminidase are able to inhibit completely the
      adhesion. Therefore, we have studied the platelet GPIIb/IIIa complex (CD41a) for
      its involvement in the adhesion of activated platelets to PMNL. The following
      evidences point to a participation of CD41a in the adhesion of activated
      platelets to leukocytes: a) inhibition of adhesion by monoclonal antibodies (mab)
      raised toward CD41a, b) inhibition of adhesion by peptides such as RGDS and
      echistatin, c) inhibition of adhesion by dissociation of the CD41a complex with
      EGTA, and d) inhibition of rosette formation using platelets from a
      thrombasthenic patient which have almost no CD41a in the surface membrane but a
      normal expression of CD62. It is likely that fibrinogen is involved in the
      adhesion of platelets to PMNL via CD41a, since fibrinogen increases the rosette
      formation of ADP-stimulated platelets. Furthermore, the incubation of
      unstimulated platelets with fibrinogen and an antibody raised against
      glycoprotein IIIa which stimulates fibrinogen binding to the platelet surface
      results in an enlarged rosette formation.

PMID- 7505066
TI  - Peripheral blood stem cell collection with a blood cell separator.
AB  - Forty-three patients with malignant nonmyeloid diseases underwent peripheral
      blood stem cell collections on an apheresis system (Spectra, COBE BCT, Lakewood,
      CO). Collections took place during the white cell (WBC) recovery phase following
      conditioning chemotherapy. One hundred two procedures were done after
      chemotherapy alone, and 72 procedures after chemotherapy plus granulocyte-colony
      stimulating factor (G-CSF). Four centrifugal separation factors were tested. One
      and one-half patient blood volumes were processed in each procedure. The mean
      volume of the collected component was 158 +/- 16 mL. After chemotherapy alone,
      the procedures provided a mean of 0.8 x 10(8) WBCs per kg and 2.3 x 10(4) colony
      forming units-granulocyte macrophage (CFU-GM) per kg of recipient body weight.
      The mononuclear cell percentage in the components increased with the centrifugal
      separation factor from 85 to 96 percent. In parallel, platelet contamination
      increased from 2.1 to 3.8 x 10(11). The collect hematocrit ranged from 1.0 to 2.5
      percent (0.01-0.025). The collection efficiency for mononuclear cells and CFU-GM
      also increased with the centrifugal separation factors from 52 to 70 percent for
      mononuclear cells and from 55 to 68 percent for CFU-GM. Collections performed
      after G-CSF-stimulated mobilization were characterized by a higher neutrophil
      contamination independent of centrifugal separation factor, which gave a mean
      mononuclear cell percentage of 64 percent in the collected component. The average
      yield for these procedures was 2 x 10(8) WBCs per kg and 28 x 10(4) CFU-GM per
      kg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505067
TI  - Removal by white cell-reduction filters of activated platelets expressing CD62.
AB  - White cell (WBC)-reduction filters that remove more than 99 percent of the WBCs
      from platelet concentrates are rapidly being introduced into routine use. Using
      activation-dependent monoclonal antibodies and flow cytometry, platelet
      activation was evaluated before and after WBC reduction in 10 platelet
      concentrates prepared manually from whole blood obtained from five male and five
      female regular volunteer blood donors. In general no significant increases were
      found in platelet activation markers after WBC reduction using filters. However,
      if platelets were activated during preparation, increased numbers of platelets
      were found expressing the activation marker CD62, and this correlated with the
      decrease in the platelet count after WBC reduction. These observations may
      explain increased platelet loss following WBC reduction in some platelet
      components.

PMID- 7505068
TI  - Indications and guidelines for the use of hematopoietic growth factors.

PMID- 7505069
TI  - [Whipple disease].
AB  - A case of Whipple's disease (WD) initially presenting with migrating arthralgia
      and later with weight loss, malaise, fever and abdominal discomfort is reported.
      On examination the patient showed signs of malnutrition, was anaemic and pyrexial
      (37.6-38.8) and had mild abdominal distention. Retroperitoneal lymph node
      enlargement was demonstrated by CT-scanning. Gastroduodenoscopy demonstrated
      white plaques and erosions in the 2nd and 3rd part of the duodenum. Repeated
      small bowed biopsies revealed pathological changes typical of WD. The patient was
      treated with parenteral penicillin 2 MIE t.i.d. for 14 days followed by
      sulfamethoxazole 800 mg and trimethoprim 160 mg b.i.d for a year. Response to
      treatment was satisfactory. Serum alkaline phosphatase levels were raised: 324
      649 U/l (80-275) on admission and remained so following treatment.

PMID- 7505070
TI  - Location, size, and complexity of epitopes on the coat protein of beet necrotic
      yellow vein virus studied by means of synthetic overlapping peptides.
AB  - Five regions on the coat protein of BNYVV which had been shown previously to be
      involved in the formation of continuous epitopes were further analyzed by means
      of synthetic overlapping peptides. It was found that at least some of these
      regions may encompass several overlapping epitopes (or parts thereof). Four
      monoclonal antibodies (MAbs) which were known to be specific for the C-terminus
      of BNYVV coat protein (amino acids 182-188 = RTSPPGQ) were found to react with
      different sets of peptides which had either the sequence RTS, RTSP, RTSPP, or
      PPGQ in common. Two other MAbs which also had been shown previously to be
      specific for the C-terminus of BNYVV coat protein failed to react with
      overlapping decapeptides. Two epitopes which were previously located in the areas
      of amino acids 115-125 and 125-140 could now be located more precisely on the
      sequences SANVRRD (amino acids 115-121) and AESSG (amino acids 128-132),
      respectively. Replacement studies with alanine showed that not all amino acids
      within these sequences are equally important for antibody binding. On the other
      hand, amino acids outside these sequences may strongly influence the reactivity
      of epitopes. The accessibility of amino acid sequences on the particles of BNYVV
      is discussed.

PMID- 7505071
TI  - T-helper cell epitopes on the E-glycoprotein of dengue 2 Jamaica virus.
AB  - To identify T-helper (Th)-cell epitopes, we analyzed 25 synthetic peptides, which
      included most of the 495-amino-acid sequence of the envelope (E)-glycoprotein of
      dengue 2 virus. The peptides were analyzed in three mouse strains, BALB/c (H-2d),
      C57BL/6 (H-2b), and outbred NIH-Swiss, for their ability to elicit antibody or
      prime the Th-cell compartment following two inoculations in Freund's incomplete
      adjuvant. Sixteen peptides were able to elicit an antipeptide antibody response
      in one or more mouse strain. Eleven antipeptide serum pools were able to bind to
      virus in ELISA. Fifteen peptides primed one or more haplotype for an in vitro
      antipeptide Th-cell response as measured by blastogenesis. Th-cell activation was
      generally confirmed by measurable in vitro production of interleukin (IL)-2/IL-4.
      Nine peptides that were positive for in vitro blastogenesis, 1-2, 35, 4-6, 79,
      142, 208, 06, 16, and 17, elicited virus-reactive Th-cells in vitro in H-2d mice.
      Two of these peptides (4-6 and 17) were able to prime virus-reactive Th-cells in
      H-2b mice. Nine peptides primed outbred mice in vitro for an antiviral antibody
      response significantly greater than that seen in animals primed with an
      irrelevant peptide. These results correlate with, and expand on, our previous
      observations based on a smaller set of synthetic peptides derived from the E
      glycoprotein of Murray Valley encephalitis virus and suggest that synthetic
      peptides can function as E-glycoprotein Th-cell epitopes. The similarity of
      results between two distantly related flaviviruses suggests that E-glycoprotein
      Th-cell epitopes are consistent in location and activity.

PMID- 7505072
TI  - Replication of barley yellow dwarf virus satellite RNA transcripts in oat
      protoplasts.
AB  - A small RNA associated with an isolate of barley yellow dwarf virus (BYDV) has
      been described which has the physical properties of a satellite RNA (Miller et
      al., Virology 183, 711-720, 1991). Here we demonstrate that this RNA has the
      biological properties of a satellite RNA: it requires the presence of helper
      virus (BYDV genomic) RNA for replication and the helper RNA does not require the
      satellite. To obtain pure satellite RNA, a permuted dimeric clone was constructed
      from which infectious satellite RNA could be transcribed in vitro. The dimeric
      transcript self-cleaved to produce monomeric satellite RNA. When this RNA was
      coelectroporated with BYDV genomic RNA into oat protoplasts, replication of both
      RNAs was detected by Northern hybridization. The RPV, but not the PAV, serotype
      of BYDV supported satellite RNA replication. The presence of discrete oligomeric
      forms of (+) and (-) sense satellite RNA in infected protoplasts suggests that
      both strands replicate by a rolling circle mechanism.

PMID- 7505073
TI  - Fine mapping of a continuous epitope on VP7 of bluetongue virus using overlapping
      synthetic peptides and a random epitope library.
AB  - Two complementary techniques have been used to delineate an epitope on VP7 of
      bluetongue virus. Two MAbs (F10 and D11), both of which bound within a region
      spanning amino acids 255 to 274 in the 349 amino acid protein, were used to probe
      overlapping synthetic peptides covering this region. A pentapeptide, QYPAL, and a
      hexapeptide, QY-PALT (amino acids 259-264), preferentially bound both MAbs. MAb
      F10 also reacted with a heptapeptide (TAEIFNV) immediately adjacent to QYPALT.
      The MAbs were also used to affinity-purify fusion phages from a random
      hexapeptide library. All phage peptides selected were similar to QYPALT.
      Comparison of the peptides suggested that residues Q and P at positions 1 and 3
      were critical for recognition. Some affinity-purified phages displayed the
      hexapeptide QYPSLL, which is similar to a sequence in VP7 of another orbivirus,
      epizootic hemorrhagic disease virus. This finding allowed a potentially cross
      reactive site to be identified.

PMID- 7505074
TI  - Mechanism of interferon action motif I of the interferon-induced, RNA-dependent
      protein kinase (PKR) is sufficient to mediate RNA-binding activity.
AB  - The interferon-induced P1/eIF-2 alpha protein kinase cDNA, designated PKR, was
      expressed both in Escherichia coli and in transfected monkey COS cells. TrpE-PKR
      fusion proteins and PKR nonfusion proteins were examined for their RNA-binding
      activity by Northwestern blot analysis. PKR is a RNA-binding protein that
      possesses two copies of a highly conserved motif, RI and RII, within the N
      terminal region of the protein. Amino acid residues between 11 and 243 of PKR,
      which includes both copies of the R motif, displayed RNA-binding activity
      comparable to that of the full-length 551-amino-acid PKR protein. Analysis of
      substitution and deletion mutant PKR proteins revealed that motif RI was both
      necessary and sufficient for RNA-binding activity, whereas motif RII was not.
      Substitution of the highly conserved lysine at position 64 within the RI motif
      abolished RNA-binding activity, both of full-length PKR and the N-terminal 243
      amino-acid truncated PKR. Finally, PKR substitution and deletion mutant cDNAs
      deficient for kinase function were expressed to much higher levels in transfected
      monkey cells than was the full-length wild-type PKR cDNA.

PMID- 7505075
TI  - [Progress in adjuvant and palliative chemotherapy of colorectal cancer: current
      status and perspectives].
AB  - After 3 decades of intense investigation some important advances have been made
      in the management of patients with colorectal cancer. Adjuvant chemotherapy
      trials in colon cancer have indicated a significant decrease in recurrence and a
      prolongation of survival when 5-fluorouracil (5-FU) plus levamisole are
      administered to patients with potentially curable tumour which has, however,
      spread to locoregional lymph nodes. Recent trials in stage II and III rectal
      cancer have demonstrated a comparable advantage for postoperative adjuvant 5-FU
      combined with radiation therapy. In the setting of metastatic disease, both in
      the presence and absence of clinical symptoms, it seems also likely that certain
      palliative regimens integrating biochemical modulation of 5-FU will result in a
      survival benefit without affecting the quality of life. According to continuing
      worldwide, interdisciplinary and cooperative study efforts, further improvements
      in current standard treatment approaches are likely to be achieved in the near
      future.

PMID- 7505076
TI  - [Mobilization of circulating hematopoietic stem cells by granulocyte colony
      stimulating factor after chemotherapy in multiple myeloma].
AB  - Due to the relatively low tumour cell contamination of peripheral blood in
      patients with multiple myeloma, autologous transplantation of circulating stem
      cells may have theoretical advantages over autologous bone marrow
      transplantation. In four patients with multiple myeloma who where considered
      potential candidates for autologous stem cell transplantation G-CSF (600
      micrograms/day) was administered following chemotherapy in order to maximally
      increase the number of circulating progenitor cells during haematopoietic rebound
      and to facilitate progenitor cell harvest by leukapheresis. In two previously
      untreated patients the administration of G-CSF following chemotherapy according
      to the UVA protocol (ultralan, vincristine, adriamycin) greatly increased
      circulating haematopoietic stem cells from 247 to 7552 CFU-GM/ml in patient 1 and
      from 173 to 6361 CFU-GM/ml in patient 2, which by far exceeded the increase in
      progenitor cells following chemotherapy alone, namely only to 594 and 317 CFU
      GM/ml in patient 1 and patient 2, respectively. In two repeatedly pretreated
      patients, the combination of UVA and G-CSF was much less effective. Progenitor
      cells increased from 144 to 735 CFU-GM/ml in patient 3 and only from 222 to 232
      CFU-GM/ml in patient 4. In both cases, however, mobilization of haematopoietic
      progenitor cells by G-CSF following cyclophosphamide (50 and 70 mg/kg body
      weight, respectively) led to much higher CFU-GM peak values (5324 in patient 3
      and 2245 in patient 4), thus allowing an adequate harvest of mononuclear cells
      and CD 34+ cell numbers to achieve, in all probability, the prompt and complete
      reconstitution of haematopoiesis in case of transplantation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7505077
TI  - Management of vulvar carcinoma radiation toxicity, results and failure analysis
      in 44 patients (1980-1989).
AB  - A retrospective analysis was performed on 44 patients with squamous carcinoma of
      the vulva (1980-1989). Patients were divided into two subgroups, group I (n = 39)
      treated with curative intent with surgery alone or with surgery combined with
      radiotherapy and group II (n = 5) treated with palliative intent with irradiation
      alone. The five-year cancer-specific survival rate for group I was 65%. Although
      this is a group of elderly patients, it was concluded that curative therapy
      should be aggressive and concessions which lead to suboptimal treatment should be
      avoided. It is essential to achieve free surgical margins. If it is decided to
      irradiate, no concessions should be made with respect to dose or overall
      treatment time. Poor results were obtained in the group treated with palliative
      intent with a six week treatment scheme of five fractions/wk. All irradiated
      patients suffered from moist desquamation as acute side-effect. Serious late side
      effects did not occur.

PMID- 7505078
TI  - Lack of binding of peptides carrying the human platelet antigen 1 (HPA-1)
      dimorphism to purified HLA-DRw52a molecules.
AB  - The strong association between anti-HPA-1a alloimmunization and DR3, DRw52a
      phenotype in HPA-1b homozygous women suggests that these class II molecules play
      a crucial role in the immune response against HPA-1a. The diallelic system HPA-1
      results in a single amino acid polymorphism at the residue 33 of the glycoprotein
      IIIa. So, we tested the binding of peptides from the 25-42 region of the GPIIIa
      to purified HLA-DR3 and -DRw52a molecules, using a solid phase assay and a liquid
      phase peptide binding assay. No binding was demonstrated, indicating that either
      the crucial region for binding to class II molecules is not the 25-42 region, or
      that other events only occurring "in vivo" are required for binding. These
      results may also suggest an indirect role of the residue 33 for T-cell
      stimulation.

PMID- 7505080
TI  - Polyploidization by means of endoduplication in a human breast cancer cell line.
AB  - Near DNA diploid human adult solid tumors are often associated with certain near
      tetraploid cells. In an established human breast cancer cell line, Hs578T, with a
      DNA index in the hyperdiploid region, polyploid cells appeared during exponential
      growth. Among clones generated from single cells and analyzed by the video time
      lapse technique, an intraclonal interdivision time (IDT) heterogeneity is
      presented that renders endoduplication a plausible explanation for the generation
      of the polyploid cells observed. This conclusion, drawn from our IDT analysis, is
      supported by curves drawn from counting grain-positive cells during continuous
      labeling with [3H]-thymidine. Our results are compared with a parallel analysis
      of the aneuploid human breast cancer cell line MDA-231, generating intraclonal
      IDT heterogeneity, due mainly to the mitotic instability of that line, as we
      reported previously.

PMID- 7505079
TI  - [Correlation between hepatitis C virus (HVC) RNA and anti-HVC antibodies in a
      hemodialysis population].
AB  - Polymerase chain reaction (PCR) was applied to detect HCV-RNA in 75 hemodialyzed
      patients. Anti-HCV status was determined by ELISA-2 and by RIBA-2 for reactive
      samples by ELISA. ALT levels were monthly determined during the year preceding
      the end of the study. For 60 patients, anti-HCV serology was known since 1989 and
      39 of them were tested for the presence of HCV-RNA at least four times during the
      2 preceding years. The 9 patients who were negative for anti-HCV antibodies were
      negative by PCR. Of the 7 patients with an indeterminate profile by RIBA-2, 3
      were positive by PCR: 1/1 with C-33c band only and 2/6 with C22-3 band only. Of
      the 59 patients reactive by RlBA-2, 57 were HCV-RNA positive. Of the 2 HCV-RNA
      negative patients, one had been PCR positive before interferon therapy. Of the 38
      patients without acute hepatitis tested by PCR on 5 successive samples, all the
      specimens of 11 and 23 patients were HCV-RNA negative and HCV-RNA positive
      respectively. In 4 patients, a transient viremia was observed. The group of HCV
      RNA positive patients had mean ALT levels greater than those who were negative. A
      correlation was established between HCV infection and both the time on dialysis
      and the number of blood transfusions. A high concordance (97%) was observed
      between antibodies to HCV and HCV-RNA.

PMID- 7505081
TI  - Analysis of epidermal growth factor receptor gene expression in stained smears
      and formalin-fixed, paraffin-embedded cell pellets by reverse transcription
      intron differential polymerase chain reaction.
AB  - Previous studies have demonstrated quantitation of epidermal growth factor
      receptors (EGFR) to be of prognostic significance in breast, bladder, esophageal
      and other neoplasms. However, the relatively large quantity of unfixed tissue
      required for epidermal growth factor radioligand binding assays (RLBA) has
      precluded its application to cytologic specimens and small biopsy specimens. For
      this reason we evaluated reverse transcription intron differential polymerase
      chain reaction (RTIDPCR) as an assay of EGFR gene expression. Squamous cell
      carcinoma (A431 and SiHa), transitional cell carcinoma (HT1376, T24, RT4),
      mammary (MCF7) and endocervical (HeLa) adenocarcinoma, and leukemia (K562) cell
      lines were used to compare RTIDPCR and RLBA. RTIDPCR involved reverse
      transcription of RNA and amplification of cDNA using primers for beta-actin and
      EGFR. Good agreement was observed between the RLBA and RTIDPCR results. RNA
      extracted from fresh cells, Diff-Quik-stained smears and formalin-fixed, paraffin
      embedded cell pellet sections yielded similar results. These data suggest that
      RTIDPCR may be useful in evaluating gene expression by cells processed as
      cytologic specimens.

PMID- 7505082
TI  - Keratins 6, 13 and 19. Differential expression in squamous cell carcinoma of the
      head and neck.
AB  - One hundred forty-one head and neck squamous cell carcinomas were analyzed for
      keratin (K) 6, 13 and 19. Staining was evaluated by light microscopy (with or
      without grading) and image analyzer and expressed as a percentage of positive
      versus all tumor surface (PSA). Both techniques rendered strongly correlated
      results. Strong expression was noted in 108 carcinomas (76.1%) for K6, in 18
      (12.7%) for K19 and in 21 (14.8%) for K13 (P = .001). One hundred thirty-six
      (96%) tumors were positive for K6, and their PSA ranged from 0.6% to 48.8%; K19,
      48 cases (0.2-44%); K13, 59 (0.2-38.1%). Expression of K6 was related to
      differentiation. K19 was expressed mainly in moderately and poorly differentiated
      tumors, and K13 was manifest more in well-differentiated carcinomas or in
      keratinized areas of less-differentiated ones. Nineteen (13.38%) tumors were
      positive for both K13 and K19. K19 thus was related to tumor progression and K13
      to differentiation. There was no correlation with tumor site or TNM category.

PMID- 7505083
TI  - Simultaneous quantitation of DNA and nucleolar organizer regions by image
      cytometry.
AB  - This paper describes a DNA/nucleolar organizer region-associated protein (NOR)
      double staining technic and quantitation method. On smeared cell slides, the
      acidic proteins associated with nucleolar organizer regions were revealed by the
      silver colloid technic, and DNA was stained with the fluorescent dye Hoechst
      33342. The simultaneous quantitation of silver stained proteins (AgNORs) and DNA
      was performed with image cytometry. Two applications of this method are
      presented: a study of AgNOR expression during the MCF-7 cell line cycle and the
      simultaneous quantitation of DNA and AgNORs in non-Hodgkin's lymphoma node
      imprints. This method offers the advantage of evaluating, on the same cell at the
      same time, the DNA content (ploidy) and AgNOR expression, which constitute a good
      approximation of the cell's proliferation state. Since ploidy and proliferation
      index are being used more and more in tumor assessment, it is useful to obtain
      them in minimum time and with a minimum of biologic material.

PMID- 7505084
TI  - Oral antihistamines/decongestants and breastfeeding.

PMID- 7505085
TI  - Maternal serum screening for chromosome defects: human chorionic gonadotropin
      versus its free-beta subunit.
AB  - The addition of maternal serum intact hCG (MShCG) to routine maternal serum alpha
      fetoprotein screening for Down's syndrome is expected to yield a detection
      efficiency around 60% for an amniocentesis rate approximating 5%. We compared the
      detection rate using intact MShCG and free-beta hCG in 480 normal pregnancies and
      48 with chromosome defects (Down's syndrome 31, other chromosome defects 17). No
      significant difference in detection efficiency was determined. However, since the
      false-positive rate with free-beta hCG was almost twice that found with intact
      hCG, and the detection rate for other chromosome defects was more than double,
      the intact MShCG assay is currently preferred. Free-beta hCG earlier in gestation
      may, however, ultimately prove superior in maternal screening for chromosome
      defects.

PMID- 7505086
TI  - Identification of naturally occurring peptides associated with MHC molecules.

PMID- 7505087
TI  - The ligands of the class II major histocompatibility complex-restricted T cells.

PMID- 7505088
TI  - Sugar-binding sites with specificity to N-acetyl-D-glucosaminides in middle ear
      mucosa of the guinea pig.
AB  - The distribution of sugar-binding sites was analyzed in Lowicryl K4M-embedded
      guinea pig middle ear mucosa. Four neoglycoproteins and a glycoprotein were used
      as probes: N-acetyl-D-glucosamine (GlcNAc), D-mannose, N-acetyl-D-galactosamine,
      or L-fucose carrying bovine serum albumin (BSA) and asialofetuin with terminal D
      galactosyl sugar residues. Each probe was then labelled with 15 nm colloidal
      gold. Incubation of ultrathin sections with gold-labelled p-aminophenyl N-acetyl
      beta-D-glucosaminide-BSA (GlcNAc/BSA/gold) led to binding on mucosal cilial,
      microvilli, rough endoplasmic reticulum, mitochondria, and nuclei. No binding
      occurred with asialofetuin or neoglycoproteins containing mannose, N
      acetylgalactosamine or fucose. Various control experiments showed that
      specificity of GlcNAc/BSA/gold binding was directed towards N-acetylglucosaminyl
      residues expressed on the neoglycoprotein. Competitive sugar inhibition with
      GlcNAc and its derivatives suggested that the strong affinity for GlcNAc-binding
      sites took place in a complex formation with sugar residues bound to a carrier
      protein. The existence of a hydrophobic region close to the sugar-binding site
      was also suggested.

PMID- 7505089
TI  - Relationship of monoclonal antibody (KHRI 3 epitope) to cochlear supporting cell
      microvilli in the guinea pig.
AB  - As reported previously, monoclonal antibodies can be generated that bind against
      guinea pig cochlear structures. Preliminary immunohistochemical characterization
      revealed that one of these monoclonal antibodies (KHRI 3) most probably binds
      against a surface structure of guinea pig cochlear supporting cells. This study
      was undertaken to further characterize the KHRI 3 epitope in the cochlea. Since
      KHRI 3 immunolabeling appeared to be punctate and epitope expression was most
      pronounced in the reticular lamina, we hypothesized that KHRI 3 epitopes are
      related to microvilli. To prove this hypothesis immunoelectron microscopy was
      used. Also investigated was how epitope expression is altered in the reticular
      lamina microvilli following drug or noise-induced changes. When
      immunocytochemical results were compared to scanning electron microscopy
      findings, a striking correlation could be seen between changes in KRHI 3
      immunolabeling and changes in the distribution of microvilli. These findings
      support the assumption that KHRI 3 epitopes are related to microvilli of inner
      ear supporting cells.

PMID- 7505090
TI  - Carcinoma of the penis. Treatment by surgery or combined bleomycin and radiation
      therapy.
AB  - Forty-four patients with squamous cell carcinoma of the penis stage T1-T2, N0
      were either treated surgically (n = 19) or with a combination of irradiation and
      bleomycin (n = 25). The overall actuarial survival rate was 80% at 3 years, 77%
      at 5 years and 60% at 10 years. The result of irradiation treatment combined with
      bleomycin was in stage N0 equivalent to that of surgical therapy. The non
      surgical treatment had the advantage of preserved sexual ability.

PMID- 7505091
TI  - Combined bleomycin and irradiation in preoperative treatment of advanced squamous
      cell carcinoma of the vulva.
AB  - Forty-two patients with advanced squamous cell carcinoma of the vulva were
      treated with a combination regimen of bleomycin 180 mg and external irradiation
      30-45 Gy. Twenty patients had primary lesions, and 22 patients had recurrent
      disease. Fifteen (75%) of the patients with primary disease showed objective
      response (five complete and ten partial response). Four underwent surgery. Of
      these, one is alive after 60 months with no evidence of disease. Two have died of
      unrelated causes without signs of recurrence. Seventeen relapsed and died of
      carcinoma of the vulva. Median survival for patients treated for primary disease
      was 8.0 months. Thirteen (59%) of 22 patients treated for recurrence showed
      objective response (two complete and eleven partial responses). None underwent
      surgery. All these patients died of carcinoma of the vulva. Median survival was
      6.4 months. Toxicity was acceptable, and there were no treatment-related deaths.
      Even taking into account that our patients had very advanced disease, the results
      are disappointing. An increase of the radiation dose beyond the maximum of 45 Gy
      given, and more aggressive surgery, might have improved the results.

PMID- 7505092
TI  - Linkage disequilibrium between cystic fibrosis mutations and polymorphic 4-bp
      repeat within CFTR gene.
AB  - The PCR technique was used in a study of the linkage of cystic fibrosis mutations
      and a polymorphic (GATT)n repeat in intron 6 of the CFTR gene. Absolute linkage
      disequilibrium was found between the common delta F-508 mutation and the (GATT)6
      allele. This allele was also in linkage disequilibrium with other unidentified
      mutations in the CFTR gene resulting in the pancreatic insufficient form of
      disease. The frequency of (GATT)n alleles in the pancreatic sufficient form of CF
      did not differ significantly from the data obtained in the total population. The
      significance of the (GATT)n polymorphic repeat for the diagnosis of CF is
      discussed.

PMID- 7505093
TI  - Anaphylactoid or carcinoid crisis?

PMID- 7505094
TI  - The effect of intravenous cadmium on exocrine and endocrine pancreatic functions
      in conscious dogs.
AB  - This study was conducted in conscious dogs to investigate the effect of cadmium
      on exocrine pancreatic secretion and plasma levels of pancreatic polypeptide
      (PP). Mongrel dogs weighing 20-25 kg were prepared with chronic gastric and
      pancreatic fistulas, and were acclimated for 3 wk prior to studies. The dogs were
      given iv infusion of saline, secretin at 25 U/kg/h, cadmium at 0.15 mg/kg/h, or
      various combinations of these compounds. During the infusion, pancreatic juice
      and blood samples were collected at regular intervals. Secretin infusion
      stimulated pancreatic secretions. Infusion of cadmium alone had no effect on
      pancreatic secretions and plasma levels of PP. When cadmium infusion was stopped
      with the background infusion of secretin, pancreatic secretions and plasma levels
      of PP were significantly increased. This latent effect of cadmium on pancreatic
      secretions and plasma levels of PP was abolished by an iv injection of 100 mg/kg
      atropine. These results indicate that cholinergic signaling may be involved in
      the effect of cadmium on pancreatic exocrine secretions and PP release. The
      current study suggests that cadmium may have diverse physiological functions in
      both exocrine and endocrine pancreatic cells.

PMID- 7505096
TI  - Cobalt determination in serum and urine by electrothermal atomic absorption
      spectrometry.
AB  - Cobalt determinations in biological fluids are of great interest in biological or
      toxicological research programs. Cobalturia is often chosen as an indicator for a
      biological monitoring program in occupational exposure to cobalt dusts. The
      method described here derives from the IUPAC reference method for nickel
      determination. It enables cobaltemia and cobalturia to be measured in small
      samples (1 mL). The mean usual values for cobalt in biological fluids are very
      low (2.7 nmol L-1 for serum and 6.7 nmol L-1 for urine), and therefore, thus
      require an analytical procedure with preconcentration and extraction. The sample
      is mineralized by wet acid digestion. After digestion, inorganic cobalt is
      extracted in form of ammonium pyrrolidine dithiocarbamate complex into isobutyl
      methyl ketone and measured in the organic layer by electrothermal atomic
      absorption spectrometry. The analytical parameters are described in detail. The
      extraction output is about 99%. The detection limits are 1.93 and 1.89 nmol L-1
      for serum and urine, respectively. Sensitivity (expressed as the concentration
      that gives a 0.044 absorbance) is 3.4 nmol L-1 for serum and 3.3 nmol L-1 for
      urine. Within-run precision ranged between 3.9 and 2.5% (coefficients of
      variation) for serum and 4.2 and 1.1% for urine, at 87 and 136 nmol L-1 levels,
      respectively. Between-run precision ranged between 4.3 and 3.3% (coefficients of
      variation) for serum and 4.2 and 2.3% for urine, at 87 and 136 nmol L-1 levels,
      respectively. At very low concentration, 5.7 nmol L-1 for serum and 2.5 nmol L-1
      for urine, the between-run precision is, respectively, 19.5 and 28%. Linearity is
      effective between 0 and 272 nmol L-1. Interferences and matrix effects are
      negligible for urine, serum, or plasma samples without hemoglobin. The method is
      easily applicable for routine determinations.

PMID- 7505098
TI  - Changes of the Cu and Zn contents in lung and liver in intestinal ischemic
      reperfusion and general ischemic reperfusion in rabbits.
AB  - The changes of pulmonary and liver Cu-Zn contents were determined and evaluated
      in intestinal ischemic reperfusion (IIR) and general ischemic reperfusion (GIR)
      of rabbits. The contents of pulmonary Zn and liver Cu were found to be lower, and
      Cu/Zn ratio increased in lung tissue and decreased in liver tissue in IIR. The
      contents of pulmonary Zn were increased, and the contents of liver Cu were
      decreased; Cu/Zn ratio also decreased in both tissues in GIR. Pulmonary Cu and
      liver Zn contents were not changed in IIR and GIR. These results showed that
      lower or higher Zn in lung tissue and lower Cu in liver tissue were related to
      the acute tissue injury during IIR and GIR, suggesting that regulating the state
      of pulmonary Zn and liver Cu should be attempted during the prevention and
      treatment of both ischemic reperfusions.

PMID- 7505095
TI  - The effect of exercise and zinc supplement on the hematological parameters in
      rats.
AB  - This study evaluates the consequences of a session of intensive short-duration
      exercise and Zn supplementation on different hematological variables. Forty male
      Wistar rats were divided into four groups (n = 10): the first nonsupplemented,
      maintained at rest (R); the second nonsupplemented, undergoing exercise (E); the
      third supplemented with Zn, kept at rest (ZnR); and the fourth supplemented with
      Zn, undergoing exercise (ZnE). Zinc supplements (200 ppm) were given in drinking
      water. The exercise consisted of a single session of swimming until exhaustion.
      At rest, RBC, Hb, and Hto fell (p < 0.05), whereas red cell indices, MCV, and MCH
      rose (p < 0.05) in +ZnR compared with R; MCHC remained unchanged (ZnR vs R).
      After exercise, RBC, Hb, and Hto increased significantly in E and in ZnE compared
      with R and ZnR, respectively. In addition, RBC and Hb were lower (p < 0.01) in
      ZnE compared with E; however, MCV and MCH were higher (p < 0.05) in the group ZnE
      vs E. With respect to white blood cells--leukocytes (WBC), lymphocytes (LYMPH),
      and neutrophils (NEUT)--no significant differences were observed between groups
      at rest (ZnR vs R). WBC and LYMPH increased significantly in E with respect to
      the rest situation (E vs R), but this did not happen in supplemented animals (ZnE
      vs ZnR). Level of pH decreased after exercise both in E and in ZnE, but the fall
      was lower in the latter. We believe that a single session of swimming until
      exhaustion leads to an increase in RBC, Hb, and Hto without causing changes in
      MCV, MCH, and MCHC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505097
TI  - The changes of metabolism balance of zinc and copper in gastric juice with widely
      varying dietary zinc intake.
AB  - The concentrations of zinc and copper in gastric juice of humans who had widely
      varying dietary zinc intake were evaluated. In order to compare this with zinc
      and copper levels of normal dietary individuals, we also determined the zinc and
      copper levels in healthy individuals' plasma and in cancer patient's natural
      tissue, all of whom had normal diets. The correlation coefficients between zinc
      and copper were 0.71, 0.45, and 0.55, respectively, in gastric juice, plasma, and
      tissue of normal dietary subjects. Such correlation changed and was destroyed
      when there was a high zinc level in gastric juice. When gastric juice zinc level
      changed from mean value 16.8 mumol/L to 262.5 mumol/L, the correlation
      coefficient varied from 0.71 to -0.04, and the copper level also varied from mean
      value 8.96 mumol/L to 4.89 mumol/L. These findings probably give the evidence to
      suggest that a high zinc level will restrain the copper level and break the
      balance of the human body's zinc and copper metabolism.

PMID- 7505099
TI  - Erythrocyte catalase activity in chronic renal failure patients and donors in the
      presence of metal ions.
AB  - The effect of hemodialysis on erythrocyte catalase (CAT) activity was studied in
      chronic renal failure (CRF) patients. This enzyme was analyzed in vitro, and its
      activity throughout the incubation period was found to be 34% lower than in
      healthy donors. The influence of Al3+, Cu2+, and Ni2+ on CAT activity in donor's
      blood (in vitro) is also studied, for short incubation periods at trace levels of
      2.5, 0.25, and 0.196 mM, respectively. With Al3+ and Cu2+, there is a decrease in
      the enzyme activity. With Ni2+, there is at first a similar decrease, followed by
      a recovery in activity up to control values.

PMID- 7505100
TI  - Dephytinization of a rat diet. Consequences for mineral and trace element
      absorption.
AB  - Soaking of a rat diet, high in both plant phytate and phytase, progressively
      degraded the phytate content with time of soaking. This dephytinization in turn
      enhanced the digestion of feed organic matter in the animals, and it
      significantly improved the absorption and retention of minerals and trace
      elements as observed in balance studies. Incorporation of elements into specific
      tissues was evaluated as a reflection of bioavailability. Some tissues did
      reflect the preceding absorption of certain elements; other tissues seemed less
      suitable as indicators of trace element absorption. Dietary calcium addition in
      many ways contrasted the soaking procedure: inorganic calcium addition to the
      feed reduced phosphorus, magnesium, and trace element bioavailability, and
      interfered with the internal deposition of the elements. The external
      dephytinization of the feed did not affect the phosphohydrolase activity of the
      intestinal mucosa as manifested by alkaline phosphatase activity or phytase
      activity. The mucosal phytase and alkaline phosphatase activities were, however,
      mutually correlated, supporting the view that "phytase" activity is a less
      substrate-specific action of alkaline phosphatase activity or a fraction of this
      activity.

PMID- 7505101
TI  - Effects of arsenic on DNA synthesis in human lymphocytes stimulated by
      phytohemagglutinin.
AB  - Effects of arsenic on DNA synthesis in human lymphocytes were biphasic: either
      trivalent (arsenic trioxide and sodium arsenite) or pentavalent (sodium arsenate)
      arsenic compounds at very low concentrations enhanced DNA synthesis in human
      lymphocytes stimulated by phytohemagglutinin (PHA), whereas higher concentrations
      inhibited DNA synthesis. There were differences among individual susceptibilities
      to arsenic-induced DNA synthesis. Either stimulating or inhibiting effects of
      trivalent arsenic on DNA synthesis in PHA-stimulated lymphocytes were always
      stronger than those of pentavalent arsenic. It was also shown that both trivalent
      and pentavalent arsenic could be rapidly taken up into the human lymphocytes, and
      immediately stimulated or inhibited DNA synthesis. A possible dual effect of
      arsenic at very low concentrations as both comutagen and inhibitor of mutagenesis
      is discussed.

PMID- 7505102
TI  - Selenium depletion in patients on home parenteral nutrition. The effect of
      selenium supplementation.
AB  - Severe selenium (Se) depletion was found in nine patients receiving long-term
      home parenteral nutrition because of short bowel syndrome. Plasma Se ranged from
      0-0.51 (median 0.21 mumol/L), and erythrocyte Se ranged from 0.7-2.6 (median 1.8
      mumol/gHgb), which was significantly lower than in the controls. Glutathione
      peroxidase (GSHPx) in plasma and erythrocytes was also decreased. After bolus
      injections with 200 micrograms Se/d in the form of sodium selenite for 4 mo,
      followed by 100 micrograms/d for 8 mo, plasma Se increased to values slightly but
      significantly higher than in the controls. Erythrocyte Se reached normal levels
      in most of the patients after 4 mo substitution, but it remained lower than in
      the controls. Following Se supplementation, plasma and erythrocyte GSHPx did not
      differ between patients and controls. These data suggest that all patients
      receiving long-term parenteral nutrition because of short bowel syndrome should
      receive at least 100 micrograms sodium selenite/d when given as bolus injections
      to avoid Se depletion.

PMID- 7505103
TI  - Influence of sodium selenite on 203Hg absorption, distribution, and elimination
      in male mice exposed to methyl203Hg.
AB  - To study the effects of long-term selenium supplementation on absorption,
      distribution, and elimination of methylmercury (MeHg) in mice, three groups of
      male mice (Balb/c CA) were exposed for 7 wk to 0, 0.6, and 3 ppm sodium selenite
      in tap water. They were then given a single oral dose of Me203Hg (2 mumol/kg) by
      gastric intubation, and elimination of 203Hg was followed by whole-body counting
      for 49 d at the same Se exposure as previously. Twenty-four hours and 49 d after
      dosage, 6-7 animals/group were sampled for analysis of 203Hg distribution in the
      body. Glutathione peroxidase (GSH-PX) activity in blood and selenium levels in
      the liver were used as measures of selenium status. Gastrointestinal absorption
      of Me203Hg was not influenced by the Se status of the animals. Selenium
      supplementation of MeHg-exposed mice caused an enhanced whole-body elimination of
      Hg, but selenium-supplemented animals did not have lower Hg levels in the brain
      and kidney than nonsupplemented animals. The effect of selenium on the
      accumulation of Hg in the brain was dose-dependent, a high dose (3 ppm Se)
      causing a higher initial accumulation of Hg. The intracellular distribution of
      203Hg in the liver and kidney was not affected by Se. The results indicate that
      selenium treatment of MeHg-exposed mice may have a positive effect on the health
      of the animals by decreasing the total body burden of MeHg.

PMID- 7505104
TI  - A randomised trial of three or six courses of etoposide cyclophosphamide
      methotrexate and vincristine or six courses of etoposide and ifosfamide in small
      cell lung cancer (SCLC). II: Quality of life. Medical Research Council Lung
      Cancer Working Party.
AB  - A total of 458 eligible patients, from 21 centres, with microscopically confirmed
      SCLC were allocated at random to three chemotherapy regimens, each given at 3
      week intervals. In two regimens, etoposide, cyclophosphamide, methotrexate and
      vincristine were given for a total of either three courses (ECMV3) or six courses
      (ECMV6). In the third regimen, etoposide and ifosfamide were given for six
      courses (E16). Patients with limited disease also received radiotherapy to the
      primary site after the third course of chemotherapy in all three groups. As
      reported by clinicians, 59% of the ECMV3, 67% of the ECMV6 and 63% of the EI6
      patients experienced moderate or severe adverse reactions to their chemotherapy.
      The major symptoms of disease, cough, haemoptysis, chest pain, anorexia, and
      dysphagia, were palliated in 63% or more of patients and the median duration of
      palliation was 63% or more of survival, the results being similar in the three
      groups. Among patients with poor overall condition, physical activity and
      breathlessness on admission, the proportions who improved were higher in the EI6
      group but the differences were small. In all three groups, levels of anxiety fell
      substantially during treatment. Levels of depression were lower and showed little
      change. As assessed by patients using a daily diary card, the patterns of nausea,
      vomiting, activity and mood, associated with courses of chemotherapy were very
      similar in the three groups. In the EI6 group there was less dysphagia and better
      overall condition between courses, but these advantages need to be weighed
      against the inconvenience of the 24-h infusions required, compared with the 30
      min infusions of the other two regimens. As reported in the companion paper (MRC
      Lung Cancer Working Party, 1993a) there was no statistically significant survival
      advantage to any of the three regimens, although the results do not exclude the
      possibility of a minor survival advantage with the two six-course regimens. In
      conclusion, there was no major clinical gain from continuing chemotherapy beyond
      three courses or from using the ifosfamide regimen.

PMID- 7505105
TI  - Hospice management of patients receiving cytotoxic chemotherapy: problems and
      opportunities.
AB  - In Britain, the specialty of palliative medicine continues to develop,
      encouraging the referral of patients early in the palliative phase of their
      illness. This had led to an increased number of patients receiving palliative
      chemotherapy and hospice care concurrently, posing special problems to the
      professionals involved. In this retrospective study, 52 patients were identified
      who received chemotherapy and hospice care simultaneously. Case notes were
      reviewed to reveal problems arising from sharing the duty of care. The poor
      quality of communication between professionals, perhaps reflecting a limited
      understanding of the various roles in patient care, we found to cause significant
      difficulties. The duration and discontinuation of cytotoxic therapy seems to be a
      particularly difficult matter. Hospice admission often signalled the end of this
      treatment. In a third of the patients, no decision was taken to stop chemotherapy
      despite the last dose being an average of just 1 week before death. The value of
      chemotherapy for patients who are too ill to return home is questioned. Seven
      patients were diagnosed as suffering from chemotherapy-induced sepsis and
      neutropenia either by hospice inpatient or home care teams, and were admitted to
      their acute centres accordingly. Most patients who died during the study period
      received terminal care in the hospice. Suggestions are made on improving
      professional education and communication, including the use of a 'chemotherapy
      card'.

PMID- 7505106
TI  - Flushable exo-endodrainage: a modified palliative approach to non-resectable
      malignant biliary obstruction.
AB  - The introduction of new imaging techniques has markedly improved the diagnosis of
      hepatobiliary disorders. Due to their anatomic situation, a substantial
      percentage of malignancies located near the hilus is not suitable for surgical
      management. We discuss an effective palliative intervention to relieve jaundice.
      In many instances drainage is a superior choice when biliodigestive anastomoses
      are not technically feasible and palliative resection carries a high complication
      rate. We present an irrigatable exo-endodrainage method employing a modified port
      a-cath system as a new alternative. In four patients, all older than 75 years,
      this system was implanted because of jaundice due to unresectable malignant
      stenosis of the extrahepatic bile duct. One patient (80 years old) died of pre
      existing acute necrotizing pancreatitis, although hyperbilirubinemia was found to
      decrease on the 7th postoperative day. The other three patients showed complete
      normalization of their bilirubin levels and their port-a-cath systems remained
      open until their death (at 3 weeks, 6 months and 7 months respectively).

PMID- 7505107
TI  - Cryosurgery: its role in liver tumours.

PMID- 7505108
TI  - Polyclonal activation of immature B cells by preactivated T cells: the role of IL
      4 and CD40 ligand.
AB  - It is well-established that preactivated CD4+ T cells can activate mature B cells
      in a polyclonal, MHC-unrestricted fashion. We have used this system to
      investigate the effects of T cell-derived signals on immature B cells purified
      from the spleens of neonatal mice, since these cells are unresponsive to many
      polyclonal activators and are exquisitely sensitive to tolerization. We show that
      immature B cells can be induced to proliferate by anti-CD3 activated, fixed Th1
      and Th2 cells, although the latter induce a greater response than the former.
      Antibodies to IL-4 partially blocked stimulation by Th2 cells, whereas antibodies
      to IL-2 and IL-5 had no effect on responses to Th1 cells. This suggested that
      molecules in addition to IL-4 contribute to the capacity of T cells to induce B
      cell activation, one likely candidate being the ligand for CD40. We therefore
      generated mouse erythroleukemia (MEL) transfectants which express CD40 ligand
      (CD40L). These transfectants also induced proliferation of immature B cells,
      which is enhanced by IL-4. Unlike the situation with mature B cells, both anti-mu
      and anti-delta antibodies inhibited the activation of immature B cells by CD40L
      MEL cells. However, this inhibition was reversed by IL-4, which synergized with
      signals delivered through CD40 to render immature B cells refractory to negative
      signals delivered through sIg. Taken together these data suggest that immature B
      cells can be activated by T cell-derived contact signals and that CD40L-CD40
      interactions, in the presence of IL-4, are capable of abrogating the negative
      signals generated via sIgM and sIgD receptors expressed by these cells.

PMID- 7505109
TI  - CD45RO+ memory T cells but not CD45RA+ naive T cells can be efficiently activated
      by remote co-stimulation with B7.
AB  - Co-stimulatory signals are absolutely required for T cell activation after TCR
      MHC-peptide interaction. The most important co-stimulatory signal known so far is
      mediated by the interaction of CD28 on T cells with B7 on APC. Here we
      demonstrate that the co-stimulatory signal from the B7 molecule does not
      necessarily have to come from the same cell which presents antigen. Titration
      curves obtained by limiting the amount of anti-CD3 mAb suggests that the same
      amount of TCR-CD3 cross-linking is required for full T cell activation whether B7
      is present on the same or on another cell, but that the kinetics of T cell
      activation is slower when B7 is present on a separate cell from the primary
      signal. Finally and most importantly we also show that CD45RO+ memory T cells,
      but not CD45RA+ naive T cells, can be efficiently activated when B7 is expressed
      on bystander cells. These findings imply that co-stimulatory activation
      requirements of B7 are more stringent for naive than for memory T cells, which
      could be an important mechanism involved in the maintenance of self-tolerance.

PMID- 7505110
TI  - MHC class I H-2Kd-restricted antigenic peptides: additional constraints for the
      binding motif.
AB  - The previously defined binding motif of MHC class I H-2Kd-restricted antigenic
      peptides consists of a Y residue in position P2 and a hydrophobic residue with a
      large aliphatic side chain (L, I, or V) in position P9/P10 of optimal 9- or 10
      mer peptides. We show now that the presence of a charged or a F residue in
      position P5 reduces the Kd-restricted competitor activity of several cytotoxic T
      lymphocyte (CTL) epitopes and model peptides, at a degree comparable to A
      substitutions for the P2 or the P9/P10 anchor residues. Various charged, polar,
      aromatic, and aliphatic amino acids were substituted for S256 in the CTL epitope
      Plasmodium berghei circumsporozoite (CS) 253-260 8-mer and in its CS 252-260 9
      mer form, whereas a more restricted panel of substitutions was tested in the CTL
      epitopes influenza nucleoprotein 147-155 9-mer and HLA-CW3 170-179 10-mer.
      Analysis of all the Kd-restricted epitopes so far defined also revealed an
      uncharged residue at this position. These additional structural constraints
      present in the Kd binding motif may thus improve the prediction of new epitopes
      recognized by T cells in the context of this MHC molecule.

PMID- 7505111
TI  - Amino acid replacement that eliminates kinetic traps in the folding pathway of
      pancreatic trypsin inhibitor.
AB  - The disulfide-coupled folding pathway of a bovine pancreatic trypsin inhibitor
      (BPTI) variant, in which Tyr 35 is replaced by Leu, was determined and compared
      with that of the wild-type protein. Two of the most highly populated
      intermediates in the refolding of the wild-type protein, [30-51, 14-38] and [5
      55, 14-38], did not accumulate to detectable levels during folding of this
      variant. The absence of these native-like intermediates was associated with a
      substantially increased rate of overall folding, consistent with previous results
      indicating that these species act as kinetic traps. As in the folding of the wild
      type protein, the kinetically preferred folding pathway for the mutant protein
      includes intramolecular rearrangements and intermediates with nonnative disulfide
      bonds. These results suggest that the predominance of the rearrangement mechanism
      is not simply the consequence of the stability of the kinetically trapped
      species. Rather, the rearrangements appear to arise because of conformational
      constraints in earlier intermediates.

PMID- 7505112
TI  - Discrimination among tRNAs intermediate in glutamate and glutamine acceptor
      identity.
AB  - The set of nucleotides in Escherichia coli tRNA(Gln) which facilitate
      aminoacylation by glutaminyl-tRNA synthetase (GlnRS) has been defined [Hayase et
      al. (1992), EMBO J. 11, 4159-4165]. To determine whether the glutamine "identity
      set" is sufficient to confer acceptance on a noncognate tRNA, we constructed
      tRNA(Glu) mutants with the set of glutamine recognition elements. These mutants
      were examined for aminoacylation in vitro with GlnRS and also with glutamyl-tRNA
      synthetase (GluRS) to correlate gains in glutamine acceptance with losses of
      glutamate acceptance. Incorporating glutamine recognition elements in only the
      acceptor stem or anticodon loop of tRNA(Glu) improved the specificity constant
      (kcat/KM) for aminoacylation by GlnRS. However, the introduction of all defined
      glutamine recognition elements in tRNA(Glu) resulted in a substrate with a
      specificity constant 100-fold below that for aminoacylation of tRNA(Gln).
      Including the tertiary framework of tRNA(Gln) (in addition to the glutamine
      recognition elements) in the tRNA(Glu) context further improved aminoacylation by
      GlnRS, but the specificity was still reduced compared with that of tRNA(Gln). The
      increase in glutamine acceptance was correlated for all mutants with a decrease
      in glutamate acceptance, indicating that GluRS also recognizes acceptor stem and
      anticodon sequences in cognate tRNA. The inability to completely convert
      tRNA(Glu) to glutamine acceptance with these mutations suggests that tRNA(Glu)
      contains antideterminants to glutamine identity. The analysis of these mutants
      with both enzymes revealed that there is a strong element of discrimination
      between glutamate and glutamine tRNAs associated with the anticodon. To test this
      dependence, mutants of both tRNAs were made to effect anticodon switches to the
      possible glutamate and glutamine isoacceptors. The kinetic evaluation of the
      anticodon switch mutants suggests that overlap in anticodon recognition is
      avoided through specificity for the third anticodon position coupled with
      divergent preferences for the wobble base.

PMID- 7505113
TI  - The lymphotoxin promoter is stimulated by HTLV-I tax activation of NF-kappa B in
      human T-cell lines.
AB  - The HTLV-I transcriptional activator tax was used to gain insight into the
      mechanism of lymphotoxin (LT; TNF-beta) gene induction. Tax-expressing cell lines
      produce LT biologic activity. An LT promoter (LT-293) CAT construct that
      contained an NF-kappa B site was active in the LT-producing C81-66-45 cell line,
      which contains defective HTLV-I but expresses tax. The observation that a mutated
      LT-kappa B construct (M1-CAT) was inactive in C81-66-45, confirmed the importance
      of NF-kappa B in LT gene expression. Tax was transfected into HTLV-I-negative
      human T-cell lines. Jurkat T cells stably expressing tax contained elevated
      levels of NF-kappa B that directly bound to the LT-kappa B site. Tax co
      transfected with reporter constructs into Jurkat cells maximally activated HTLV-I
      LTR-CAT and kappa B-fos-CAT and also activated LT-293 to a lesser extent. In JM T
      cells, tax induced LT-293 activity by two- to four-fold, though there was no
      induction of M1-CAT. The increase in LT-293 CAT activity mirrored the increase in
      LT biologic activity seen under these conditions. These studies, the first to
      demonstrate induction of LT promoter activity over basal levels, indicate that
      HTLV-I tax causes low-level activation of both endogenous LT and the LT promoter,
      at least in part through activation of NF-kappa B.

PMID- 7505114
TI  - BDNF and NT-3 induce intracellular Ca2+ elevation in hippocampal neurones.
AB  - The effects of neurotrophins on intracellular Ca2+ levels in rat hippocampal
      neurones were studied in vitro using fura-2 fluorescence microscopy. BDNF and NT
      3, but not NGF, rapidly increased cytoplasmic Ca2+ concentrations in these
      neurones ten-fold to reach 1 microM. Moreover in some of the neurones both BDNF
      and NT-3 elicited Ca2+ responses, indicative of the presence of functional
      receptors for these neurotrophins in the same cell. In these cultures
      approximately 80% of the hippocampal neurones were stained with antibodies
      against full-length TrkB. The expression of functional TrkB was also confirmed by
      RNA analysis. These results demonstrate the presence of functional receptors for
      BDNF and NT-3 in hippocampal neurones.

PMID- 7505115
TI  - Tyrphostin-induced inhibition of p210bcr-abl tyrosine kinase activity induces
      K562 to differentiate.
AB  - We report on the potency of two Tyrphostin tyrosine kinase blockers, AG 1112 and
      AG 568, to inhibit p210bcr-abl tyrosine kinase activity in K562 cells,
      concomitant with the induction of erythroid differentiation. AG 568 and
      especially AG 1112 represent a specific group of nontoxic protein tyrosine kinase
      blockers among more than 1,400 tested. These compounds possess therapeutic
      potential for purging Philadelphia chromosome-positive cells in preparation for
      autologous bone marrow transplantation in chronic myelogenous leukemia.

PMID- 7505116
TI  - Association of the p85 regulatory subunit of phosphatidylinositol 3-kinase with
      an essential erythropoietin receptor subdomain.
AB  - Using an active, HAI epitope-tagged form of the murine erythropoietin (EPO)
      receptor and via direct coimmunoprecipitation, the p85 regulatory subunit of
      phosphatidyl inositol-3 kinase (p85/PI3-K) is shown to associate with the EPO
      receptor in transfected FDC-P1 cell lines. Coimmunoprecipitation of p85 with
      epitope-tagged EPO receptors was observed initially in FDC-HER cells labeled
      metabolically with [32P]orthophosphate, and association of these factors was
      confirmed by Western analyses of receptor immunoprecipitates using p85 antiserum.
      Interestingly, this association occurred in the absence of ligand, and exposure
      of FDC-HER cells to EPO did not detectably affect levels of receptor-associated
      p85 or overall levels of p85 phosphorylation. However, EPO was observed to
      stimulated the rapid formation of phosphatidylinositol 32P-phosphate in FDC-HER
      and FDC-ER cells. Through baculovirus-mediated expression of epitope-tagged EPO
      receptor forms in SF9 cells, domains for p85 association were mapped. Analyses of
      receptor forms with cytosolic truncations and deletions delineated a candidate
      subdomain for p85 binding to an essential extended box-2 region (P329-E374;
      including a putative motif for SH2 binding, Y343LVL). These findings extend a
      mechanistic alignment between the EPO receptor and protein tyrosine kinase
      encoding receptors that likewise activate PI3-K, and expand the importance of
      further defining pathways to PI3-K activation.

PMID- 7505117
TI  - Alternatively spliced CD44 transcripts in diffuse large-cell lymphomas:
      characterization and comparison with normal activated B cells and epithelial
      malignancies.
AB  - CD44 exists in a variety of alternatively spliced isoforms that include variable
      numbers of additional exons from the membrane proximal domain (exons 6-14).
      Lymphocytes express high levels of a "hematopoietic" isoform (CD44H) with no
      additional variable exons. CD44H binds lymphocytes to postcapillary venules and
      promotes lymphocyte extravasation into nodal areas. Epithelial carcinomas also
      express CD44 variants, including exon 10-containing isoforms associated with
      metastasis in a rat model. An exon 10-containing CD44 isoform is also transiently
      expressed by normal activated lymphocytes, suggesting that the protein may
      function in the trafficking of both normal lymphocytes and metastatic tumors. To
      identify the specific CD44 transcripts in tumors from patients with primary
      nodal, extranodal, and disseminated large-cell lymphomas (LCLs) and compare them
      with CD44 mRNAs in normal Ig-activated splenic B cells and epithelial cells, we
      used a semiquantitative RNA-based polymerase chain reaction. Specific CD44
      variants were identified by size, hybridization with exon-specific probes, and
      sequence analysis. In comparison to primary nodal LCLs, extranodal and
      disseminated LCLs had increased levels of CD44H and additional isoforms,
      including a directly spliced (exon 5-->exon 10-->exon 15) exon 10-containing CD44
      variant. The CD44 transcripts in extranodal and advanced-stage LCLs were similar
      to those in normal Ig-activated splenic B cells, whereas epithelial malignancies
      contained decreased CD44H and increased amounts of larger CD44 variants with
      additional exons from the membrane proximal domain. The regulated expression of
      specific CD44 variants is likely to influence the trafficking of lymphoid and
      epithelial malignancies.

PMID- 7505118
TI  - Integrin alpha 4 beta 1 and glycoprotein IV (CD36) are expressed on circulating
      reticulocytes in sickle cell anemia.
AB  - The abnormal adherence of red blood cells, especially circulating reticulocytes
      (erythrocyte precursors), to the endothelium is believed to contribute to
      vascular occlusion observed in patients with sickle cell disease. Although
      several plasma proteins including von Willebrand factor and fibronectin have been
      proposed to mediate this adhesion, the mechanism of sickle cell adhesion to the
      endothelium remains unknown. Using flow cytometry, we screened sickle red blood
      cells with monoclonal antibodies (MoAbs) against known adhesion receptors and
      detected integrin subunits alpha 4 and beta 1 and the nonintegrin glycoprotein IV
      on reticulocytes but not on erythrocytes. No reactivity was detected against
      integrin subunits alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 2, beta 3,
      integrin alpha IIb beta 3, or the nonintegrin glycoprotein Ib.
      Immunoprecipitation of reticulocytes with either alpha 4- or beta 1-specific
      antibodies identified the alpha 4 beta 1 complex (alpha 4(70) and alpha 4(80)
      forms), a receptor for fibronectin and vascular cell adhesion molecule-1. An
      antibody against glycoprotein IV, a receptor reported to bind thrombospondin and
      collagen, immunoprecipitated an 88-kD protein consistent with its reported M(r).
      MoAbs against alpha 4 and glycoprotein IV bound to an average of 4,600 and 17,500
      sites per reticulocyte, respectively. Identification of alpha 4 beta 1 and
      glycoprotein IV on reticulocytes suggests both plasma-dependent and independent
      mechanisms of reticulocyte adhesion to endothelium and exposed extracellular
      matrix.

PMID- 7505119
TI  - In vitro expansion of human peripheral blood CD34+ cells.
AB  - To elucidate the role of recombinant human colony-stimulating factors (CSFs) for
      expanding peripheral blood (PB) CD34+ cells, these cells were purified up to
      94.5% +/- 1.3% and the effects of individual and combined CSFs on the
      proliferation and differentiation of these cells were studied in a 7-day
      suspension culture. The majority of CD34+ cells coexpressed CD38 (81.8% +/-
      5.1%), but was negative for CD33 (88.5% +/- 3.4%). Among the individual CSFs
      examined, recombinant interleukin-3 (rIL-3) was identified as the most potent
      factor for expanding PB progenitor cells and increased nonerythroid progenitor
      cells 13- +/- 4-fold (P < .01). Recombinant granulocyte-macrophage colony
      stimulating factor (rGM-CSF), recombinant granulocyte-CSF (rG-CSF), recombinant
      macrophage-CSF (rM-CSF), rIL-6, rIL-11, and recombinant stem cell factor (rSCF)
      did not alone expand nonerythroid progenitor cells. A combination of 5 CSFs, ie,
      rIL-3, rIL-6, rGM-CSF, rG-CSF, and rSCF, was identified as the most potent
      combination of those tested and increased nonerythroid progenitor cells 57- +/-
      11-fold. After a 7-day suspension culture of CD34+ cells with these 5 CSFs, CD34+
      cells expanded 14.5-fold, and CD34+/CD33- cells and CD34+/CD33+ cells were also
      expanded 2.9-fold and 307-fold, respectively. Most secondary colonies derived
      from expanded cells were small; however, the absolute number of large-sized
      colonies expanded 5.9- +/- 3.3-fold. Thus, the combination of CSFs can achieve a
      degree of amplification of PB CD34+ cells. The capability of in vitro expansion
      of PB CD34+ cells as an adjunct to PB stem cell transplantation is worthy of
      consideration.

PMID- 7505120
TI  - Solid-phase von Willebrand factor contains a conformationally active RGD motif
      that mediates endothelial cell adhesion through the alpha v beta 3 receptor.
AB  - The interaction of von Willebrand factor (vWF) with the alpha v beta 3 integrin
      of human umbilical vein endothelial cells is dependent on the RGD sequence
      present at residues 1744-1746 of the mature vWF subunit. We compared vWF and its
      two dimeric fragments, SpIII (residues 1-1365) and SpII (residues 1366-2050), as
      adhesion substrates. Solid-phase vWF and SpII supported endothelial cell
      adhesion, whereas SpIII, which contains the glycoprotein (GP) Ib binding domain,
      did not. Soluble SpII inhibited adhesion to immobilized ligands, whereas soluble
      vWF did not, suggesting that exposure of the cell attachment domain involves a
      conformational modification of vWF. Dendroaspin and albolabrin, two RGD
      containing peptides of the disintegrin family, were potent inhibitors of cell
      adhesion to vWF (IC50 approximately 15 nmol/L). Complete inhibition of
      endothelial cell adhesion to vWF was obtained in the presence of F(ab')2 of
      monoclonal antibody 9 to vWF, which blocks vWF binding to platelet GPIIb/IIIa. In
      contrast, monoclonal antibody 713 to vWF, which blocks its binding to platelet
      GPIb, did not inhibit cell adhesion to vWF. These results indicate that
      endothelial cell adhesion to vWF is mediated by an RGD-dependent interaction with
      alpha v beta 3, but does not seem to involve a GPIb-like receptor, and show the
      importance of the conformation of the RGD sequence.

PMID- 7505121
TI  - Platelet activation and inhibition of malarial cytoadherence by the anti-CD36 IgM
      monoclonal antibody NL07.
AB  - The surface glycoprotein CD36 (GPIV) is known to mediate the adhesion of
      Plasmodium falciparum malaria-infected red blood cells and to be a receptor for
      extracellular matrix proteins such as collagen and thrombospondin. The murine
      monoclonal IgM antibody NL07, which is specific for CD36, has now been shown to
      also be a potent inhibitor of the adhesion of P falciparum malaria-infected red
      blood cells to C32 melanoma cells. Treatment of platelets with NL07 monoclonal
      antibody resulted in rapid degranulation, release of ATP and serotonin, increase
      in [Ca2+]i, and tyrosine phosphorylation of a substrate protein of 130 kD. In
      about one-half of the experiments, activation with NL07 resulted in the formation
      of small aggregates of 10 to 30 platelets, whereas in the other half of the
      experiments, large aggregates were seen similar to those induced by adenosine
      diphosphate (ADP) and these large aggregates could be converted to the small
      aggregates by ATP alpha S or by AP-2 or other antibodies against GPIIb and/or
      IIIa. Microaggregates of 2 to 5 platelets were seen with Glanzmann's platelets
      that constitutively lack GPIIb/IIIa. Aggregate formation was not seen with heat
      treated serum, in the presence of anti C1q antibodies, or when using C5-, C8-, or
      C9-deficient human sera. Although activation of platelets with purified
      complement components results in a slow morphologic change without aggregation,
      involvement of CD36 results in rapid complement-mediated activation leading to
      formation of small aggregates that is largely independent of GPIIb/IIIa and that,
      under certain circumstances, proceeds to the formation of large ADP-dependent
      aggregates.

PMID- 7505123
TI  - Cross-linking of the beta-glucan receptor on human monocytes results in
      interleukin-1 receptor antagonist but not interleukin-1 production.
AB  - The beta-glucan receptor, found on monocytes and neutrophils, binds glucose
      polymers derived from fungi. Ligands for the receptor have various
      immunomodulatory effects, including increased microbicidal killing activity. We
      have investigated the effect of beta-glucans on the production of interleukin-1
      (IL-1) and its naturally occurring inhibitor, the IL-1 receptor antagonist (IL
      1Ra). Particulate beta-glucan induced IL-1Ra production from human peripheral
      blood mononuclear cells (PBMC) but did not stimulate IL-1 beta synthesis or gene
      expression in these same cells. Monomeric (soluble) beta-glucan did not induce IL
      1Ra production. However, when preincubated with PBMC, monomeric beta-glucan
      significantly (P < .01) reduced particulate beta-glucan induction of IL-1Ra by
      40%, suggesting that crosslinking of beta-glucan receptors is required for
      induction of IL-1Ra. In support of this, monomeric beta-glucan immobilized on
      plastic surfaces stimulated IL-1Ra production. Vitamin D3, which increases the
      functional capacity of beta-glucan receptors, increased IL-1Ra production induced
      by particulate beta-glucan, whereas dexamethasone suppressed IL-1Ra synthesis.
      Because of their differential effects on cytokine production, beta-glucans may be
      used to therapeutic advantage in the diseases in which IL-1 is implicated.

PMID- 7505124
TI  - Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a
      single apheresis.
AB  - Myeloablative treatment and peripheral blood progenitor cell (PBPC)
      transplantation are increasingly used for lymphomas and leukemias. We have sought
      to optimize conditions for priming, collection, and engraftment of the
      leukapheresis product. Fifty-four consecutive adult patients were eligible, 31
      with high-grade non-Hodgkin's lymphoma of poor prognosis, 12 with Hodgkin's
      disease in chemosensitive relapse, and 11 with poor prognosis acute lymphoblastic
      leukemia. Filgrastim was administered after routine chemotherapy with VAPEC-B or
      HiCCOM to mobilize PBPC. A rapidly increasing white blood cell count was used to
      predict the time of peak PBPC release and plan leukapheresis. Forty-five patients
      underwent leukapheresis. A median of 14 L of blood was processed at a single
      apheresis. A median of 2.4 x 10(8)/kg mononuclear cells (MNCs), 1.04 x 10(6)/kg
      granulocyte-macrophage colony-forming cells (GM-CFCs), and 10.6 x 10(6)/kg CD34+
      cells were obtained. Slightly fewer MNCs were obtained from the heavily
      pretreated Hodgkin's disease group. There were no other significant differences
      in the size or composition of the leukapheresis harvest in the three patient
      groups. Forty patients underwent high-dose therapy and PBPC transplantation.
      Filgrastim was administered by daily subcutaneous injection until the absolute
      neutrophil count was > or = 1 x 10(9)/L for 2 consecutive days. Rapid and
      sustained hematopoietic engraftment occurred in all patients. The median time to
      achieve a neutrophil count > or = 0.5 x 10(9)/L was 9 days (range, 8 to 16 days);
      to achieve a platelet count > or = 20 x 10(9)/L was 10 days (range, 6 to 88
      days); and to achieve a platelet count > or = 50 x 10(9)/L was 15.5 days (range,
      10 to 100 days). Neutrophil recovery was faster than that of a historical control
      group treated with autologous bone marrow transplantation and filgrastim, but
      platelet recovery times were halved in the PBPC group. There was no secondary
      engraftment failure. Requirements for blood and platelet transfusions, antibiotic
      use, and parenteral nutrition were similar in the three patient groups. The
      median number of days in the hospital was 13 (range, 10 to 55) in the PBPC
      patients, compared with 19 (range, 14 to 51) in the historical controls.
      Leukapheresis yields (MNC, GM-CFC, and CD34+ cell numbers) were not useful for
      predicting the times to engraftment. We have shown that sufficient PBPC for
      transplantation can be obtained at a single leukapheresis after mobilization with
      routine chemotherapy and filgrastim in patients with non-Hodgkin's lymphoma,
      Hodgkin's disease, and acute lymphoblastic leukemia, even those heavily
      pretreated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7505122
TI  - CD34-expressing human thymocyte precursors proliferate in response to interleukin
      7 but have lost myeloid differentiation potential.
AB  - CD34 is a marker for pluripotent stem cells also present on lineage-committed
      hematopoietic progenitors from bone marrow and a subpopulation of immature
      thymocytes. To characterize these early immature thymocytes, we have studied 24
      pediatric thymus samples for CD34/7 expression. Three subpopulations could be
      defined from these T-cell receptor (TcR-) immature thymocytes: CD34+7++ (12.0 +/-
      5.8), CD34-7++ (12.6 +/- 8.6), and CD34-7+ (71.5 +/- 17.0%). CD7++ represents
      upregulation of this antigen and is expressed by cells of a blast-like
      morphology. Three-color flow cytometric analysis of these three subsets suggests
      the following ordered differentiation sequence: CD34+7++1-4-8-45RA+-->CD34+7++1+
      4+8-45RA+/- -->CD34-7++1+4+8-+45RO+-->CD34-7+1++4+8+45RO+. Early immature
      thymocyte cell division is essential in the thymus to generate a large number of
      precursors before the initiation of the selection process. We observed that both
      CD2 as well CD28 activation pathways were inefficient to serve as costimulant
      with phorbol ester 12-O-tetradecanoyl phorbol 13-acetate or interleukin-2 (IL-2)
      to induce the proliferation of the three CD34/7 subsets isolated by cell sorting.
      However, whereas IL-1, IL-2, IL-3, IL-4, granulocyte colony-stimulating factor,
      and granulocyte-macrophage colony-stimulating factor were ineffective, IL-7 was a
      potent cytokine, alone or in synergy with stem cell factor (SCF) to induce
      immature thymocyte proliferation. The proliferation induced by IL-7 or IL-7 + SCF
      is restricted to the CD34+ cells and, after 4 or 8 days of culture with IL-7,
      some CD34+7++ acquire the expression of CD4 and/or CD8, but remain CD3/TcR-. We
      also tested the myeloid differentiation capacity of these CD34 immature
      thymocytes. Using two different approaches, myeloid colony formation in
      methylcellulose and limiting dilution analysis in the presence of myeloid growth
      factors, we were unable to detect myeloid differentiation capacity from CD34+
      early thymocytes, whereas CD34+7+ from bone marrow contained about 10% of the
      clonogenic cells present in the CD34+7- fraction. Together, these data support
      the concept that thymic CD34+7++ represents the earliest thymic subset of fully
      committed T-lineage cells, capable of proliferating specifically to IL-7.

PMID- 7505125
TI  - Detection of a novel double mutation in a beta-thalassemia patient by RNA single
      stranded conformation polymorphisms and direct sequencing.

PMID- 7505126
TI  - The Costello syndrome: a boy with thick mitral valves and arrhythmias.
AB  - A 3-year-old boy with Costello syndrome is reported. He had typical clinical
      features of the syndrome including severe postnatal growth retardation, poor
      sucking, mild developmental delay, a coarse characteristic facies, thick and
      loose skin of the hands and feet, sparse and curly hair, dark skin, and relative
      macrocephaly but lacked nasal papillomas. In addition, he had cardiac anomalies
      with extrasystoles and thick mitral valve tips. Mitral valve defects may be a
      clinical feature of the syndrome.

PMID- 7505128
TI  - The patent ductus arteriosus as a source of recurrent peripheral embolisations.
AB  - A patient with a multiple peripheral embolisation of unknown origin is presented.
      Because of her extreme obesity, some diagnostic procedures could not be performed
      (CAT), and some were performed with great difficulty (conventional ECHO, DSA of
      the aorta). Transesophageal echocardiography was the key procedure in the
      diagnosis of the floating thrombotic mass in the descending aorta. A surgical
      operation was performed, and a thrombus was found in the aortic orifice of the
      hemodynamically insignificant patent ductus arteriosus. The patient has now been
      18 months in good condition and free of thromboembolic events.

PMID- 7505127
TI  - William L. McGuire Memorial Symposium. Drug resistance to tamoxifen during breast
      cancer therapy.
AB  - Breast cancer is the most common malignancy occurring in Western women, and is
      one of the leading causes of cancer mortality. The nonsteroidal antiestrogen
      tamoxifen has been shown to be an effective treatment for pre and postmenopausal
      women with all stages of the disease. Tamoxifen provides effective palliation
      when used to treat patients with advanced disease, and adjuvant tamoxifen therapy
      produces significant increases in both disease-free and overall survival (Early
      Breast Cancer Trialists Collaborative Group. Lancet 339:1-15, 71-85, 1992). Data
      from the laboratory have shown that the primary action of tamoxifen is
      tumoristatic rather than tumoricidal, and long-term therapy is therefore
      recommended. Unfortunately, many patients experience disease progression while
      taking tamoxifen. Some tamoxifen resistant tumors may remain sensitive to
      alternative endocrine therapies, while others may become refractory to any
      hormonal manipulation. Many models have been developed in vitro and in vivo to
      study the progression of breast cancer growth from tamoxifen sensitive to
      tamoxifen resistant. We and others have used long-term estrogen deprivation and
      long-term tamoxifen exposure to develop cell lines and tumors capable of growth
      in the presence of clinically relevant tamoxifen concentrations. Recently our
      laboratory has also shown that mutations in the estrogen receptor can cause an
      antiestrogen-occupied receptor to behave as though it were occupied by an
      estrogen. Breast cancer is a highly heterogeneous disease and it is likely that
      the mechanisms which cause tamoxifen resistant growth are equally heterogeneous.
      Several of the models from our laboratory and others which may contribute to an
      understanding of this complex phenomenon are discussed here.

PMID- 7505129
TI  - On the development of Croatian neurology.
AB  - The author depicts the roots and the development of modern Croatian neurology. On
      the ground of cultural and civilizational predispositions it achieved an
      exceptional development during the last three decades in the period after the
      World War II. Although clinical neurology may be traced only after the foundation
      of the first Croatian medical faculty in Zagreb in 1917, until 1971 within the
      common discipline of neuropsychiatry, a vast medical literature: reports on
      neurological problems both from literature and from everyday medical praxis were
      published in Croatian after the foundation of the Croatian medical journal
      "Lijecnicki vjesnik" in 1877, written by internists or general practitioners
      interested in neurology. First Croatian textbook in neurology was published by
      Ivo Glavan already in 1935 and new editions of this book have made it a popular
      handbook for many generations of medical students and physicians, not only in
      Croatia but also in other parts of the former Yugoslavia. In the sixties the
      concept of development of subspecialized disciplines prevailed: clinical
      neurophysiology, epileptology, neuromuscular diseases, cerebrovascular diseases
      and intensive neurology, child neurology. At that time a fast growing of man
      power and institutions started, what made possible a modern concept of early
      neurologic diagnostics and treatment. The period was marked by intensive
      collaboration with teams of electrical engineers interested in bio-electronics,
      development of basic neurosciences, of neuroimaging technologies and
      neuroscintigraphy. Many initiatives came from Croatia for collaboration with
      neighbouring countries within the former Yugoslavia, but also with other
      neighbouring European countries, especially Austria, Italy and Germany, as well
      as with the American neurology.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505131
TI  - Morphological and cytochemical characteristics of atypical mononuclear cells in
      the blood of patients with the syndrome of infectious mononucleosis caused by
      Epstein-Barr virus.
AB  - On the basis of their origin and morphologic and cytochemical characteristics,
      atypical mononuclear cells (AMNC) in the peripheral blood of patients with the
      syndrome of infectious mononucleosis caused by the Epstein-Barr (EB) virus can be
      classified into three groups, from I to III. The AMNC groups I are the most
      numerous (76.36% +/- 2.50%). A larger part of these cells have the
      characteristics of more or less altered lymphoblasts and the smaller part of
      large pyroninophilic cells and "reactive immunoblasts", and meant to have
      developed from T lymphocytes. These are the most numerous in the acute phase of
      the disease, which correlates with the most significant increase of T lymphocytes
      values. A very high percentage (84.00% +/- 7.30%) of the AMNC group I contains
      acid phosphatase isoenzyme 3 and acid non-specific esterase (82.43% +/- 7.76%), a
      considerable percentage of beta-glucuronidase (58.75% +/- 13.99%), and acid
      phosphatase isoenzyme 1 (51.20% +/- 10.81%). A small percentage of these cells
      contains acid phosphatase isoenzyme 5 resistant to the action of L+tartaric acid.
      In 39.04% +/- 8.72% of the lymphocytes in the peripheral blood of the examined
      patients and in the two thirds and nearly three fourths of the AMNC group I, the
      presence of acid phosphatase manifests itself in the form of scattered granules.
      The positive reaction to non-specific esterase (pH 7.8-8) in 39.72% +/- 8.44%
      lymphocytes of the peripheral blood of the patients and in 59.26% +/- 10.09% of
      the AMNC group I manifests itself in the form of scattered granules.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7505130
TI  - The significance of immunocompromised condition in the prophylaxis of hepatitis B
      in chronic renal insufficiency.
AB  - The paper presents the immunogenicity of hepatitis vaccine (obtained by genetic
      engineering) in immunocompromised patients with preterminal renal insufficiency
      defined by depression of creatinine clearance of 10 to 25 ml/min. The study
      consisted of 28 randomized patients with impaired renal function. Sixteen
      patients received a single dose and, twelve a double dose of vaccine.
      Revaccination following 3 intramuscular doses of vaccine had been undertaken
      after 24 weeks if antibodies were not detected or their titer was 10 i. u. or
      less. All patients obtained a booster dose following 52 weeks. There was no
      statistically significant difference in titer values between immunocompromised
      patients regardless of whether they were vaccinated with a single or double dose.
      The antibody titer in patients with chronic renal insufficiency was significantly
      lower as compared with the results of vaccination in healthy population. It may
      be concluded that it is more beneficial and less expensive to use a single dose
      vaccine and revaccination if the titer is negative or insufficiently high.

PMID- 7505132
TI  - Frozen section analysis of breast biopsy specimens.
AB  - The authors compared the diagnoses from intraoperative frozen section
      consultation with the final diagnosis using permanent tissue sections from 179
      breast biopsy specimens. Of these, there were 175 correct diagnoses (97.8%), two
      diagnoses were incorrect (1.1%) and two were inconclusive (1.1%). The
      distribution of the correct diagnoses within each particular group of breast
      diseases proves that in the invasive tumor group the diagnosis on FS was correct
      for 101 patients (98.1%) and incorrect for two patients (1.9%). In the
      fibrocystic breast disease group, diagnoses correlated for 42 patients (97.7%),
      whereas the problem in diagnosing the extent of epithelial proliferation appeared
      for only one patient (2.3%) and was categorized as an inconclusive diagnosis. Of
      4 incorrect and inconclusive diagnoses, two occurred as a result of sampling
      nonrepresentative tissue specimens and two as a result of diagnostic
      misinterpretation. This study has shown that for the determination of the
      histological type of carcinoma, FS is not of significant morphological value
      since correct diagnoses were made for only 60% of the patients.

PMID- 7505133
TI  - Etiopathogenesis of nasal polyps.
AB  - An acute process is practically never the cause of polyps, for despite the
      reaction being hyperergic, it spreads through the entire circumference of the
      mucosa. In chronic noxa the infiltrates will not be diffusely distributed and may
      in certain places be too large to form protuberances in the mucosa by themselves.
      The essence of this chronic process is a further proliferation of the connective
      tissue, especially around the blood and lymph vessels. Chronic oedemas in the
      mucosa of the nose and the paranasal sinuses are transported through venous and
      lymphatic vessels towards the nasal meatus, more towards the middle one than the
      upper one. In this region not only are there lymphatic vessels, but here also
      lies the borderline between low and raised tissue pressure. That is the place
      where most nasal polyps appear. Respiratory allergy is much more frequent in
      recurrent nasal polyposis (78%) than in the group of patients with non-recurrent
      polyposis (18%). Through histochemical analysis of nasal polyps, eosinophils are
      found in both recurrent and non-recurrent polyps (74% and 44%, respectively), as
      well as in the nasal mucosa (32% vs. 15%) which is statistically significant.

PMID- 7505134
TI  - Numerical quadruplet code of human cervical carcinoma tissue proteins.
AB  - Proteins were extracted from cervical cancer tissue at 100,000 g supernatant. The
      four most abundant extracted tissue proteins form a "numerical quadruplet code",
      by which tissues can be distinguished from each other. Proteins that are specific
      for cervical cancer were a protein with a relative migration rate of 0.5,
      obtained by disc-electrophoresis, and a small protein, p 35, obtained by SDS
      PAGE. This shows that, in a malignant process, the expression of a new protein
      may occur or, more probably, an already existing protein is better expressed.

PMID- 7505135
TI  - Emotion profile and behaviour pattern of patients with active duodenal ulcer
      compared with acute coronary patients.
AB  - The authors examined personality profiles and type A/B behaviour in 100 patients
      with active duodenal ulcer, and a mean age of 39 years, using the Bortner scale
      and the Plutchnik Emotional Profile Index (EPI). The authors compared them with
      acute coronary patients and healthy controls. The mean EPI percentages for the
      duodenal ulcer patients, compared with acute coronary patients and healthy
      controls, display the trustful dimension (84.1 +/- 27.4--69.1 +/- 20.4--69.3 +/-
      20.0), the aggressive dimension (56.7 +/- 9.3--41.3 +/- 19.2--37.6 +/- 17.3), the
      depressed dimension (84.5 +/- 12.3--52.8 +/- 19.1--51.4 +/- 23.1) and the
      dyscontrol dimension (73.5 +/- 32.2--48.4 +/- 27.7--50.2 +/- 17.5) to be
      significantly higher (P < 0.005). The mean percent scores of the gregarious
      dimension (44.2 +/- 13.2--72.7 +/- 22.7--68.0 +/- 22.0), control dimension (25.2
      +/- 91.--39.1 +/- 31.9--44.3 +/- 15.5) and timid dimension (26.2 23.3--56.0 +/-
      19.9--59.8 +/- 29.5), are significantly lower in duodenal ulcer patients than in
      acute coronary patients and controls (P < 0.005). Behaviour type A was found in
      95 (95%) duodenal ulcer patients, in 76 (73.7%) acute coronary patients and in 58
      (68%) healthy controls (P < 0.001). The Bortner scale was significantly higher in
      duodenal ulcer patients than in coronary and control subjects (P < 0.005). The
      EPI of duodenal ulcer patients in comparison to acute coronary patients and
      healthy controls, are sadder, more impulsive, do more risky things and are more
      disorganized and dependent. Type A behaviour was more often in duodenal ulcer
      patients than in the coronary and control groups.

PMID- 7505136
TI  - The biomechanics of the kidney: the isothermal function of the capsule adipose
      renis.
AB  - The paper describes the research in the field of thermodynamics. It deals with
      the function of capsule adipose renis. This homogenous tissue of low temperature
      acts as an independent thermal conductor. In fact, by encapsulating the kidney,
      it acts as a vacuum-flask, providing insulation for the kidney from two
      surrounding thermal areas, the warmer being on the interperitoneum and the cooler
      on the skin surface.

PMID- 7505137
TI  - The immediate role of psychiatric staff in the resistance.
AB  - The psychiatric staff of the University Department of Psychiatry in Osijek
      University Hospital played an active and important role during the 1991/92 war.
      This grew out of the analytical approach to psycho-social relations in the
      undirectional spiritual state of mind under the communist system of Yugoslavia.
      The role of psychiatric staff in the resistance against the aggressor was
      determined by a spontaneous freedom of choice, an aspiration for permanent
      harmony of moral and legal system, mature interpersonal relations and an
      awareness of their place in the national community. Psychiatric staff investigate
      the psychology of a nation, its desires, anxieties and defense and they recognize
      their role. War makes therapeutical relationships more complex and demands almost
      daily supervision of the counter-transfer reactions towards the wounded, refugees
      and other patients who ask for or need psychiatric help. This study comments on
      the experiences of a group of staff members of the University Department of
      Psychiatry. In addition, the therapeutical phenomena in their relations with
      patients are also recognized.

PMID- 7505138
TI  - Some modular features of temporal cortex in humans as revealed by pathological
      changes in Alzheimer's disease.
AB  - The concept of cortical modularity has surfaced as a generic term that alludes to
      any grouping or periodicity within the cerebral cortex relating to its neurons
      and their processes, and the enzymes, transmitters, and metabolic markers
      associated with them. Some of the best examples of anatomical modularity have
      been described in primary sensory areas such as the visual and somatosensory
      koniocortices. Functional examples of modularity abound in these same areas but
      may or may not have known morphological and chemical correlates. We depart from
      the traditional methods of cortical neuroanatomical analysis in this report and
      describe instead pathological alterations in the cortex in Alzheimer's disease.
      In particular, we focus on the cortex of the hippocampal formation and
      entorhinal, perirhinal, and anterior inferior temporal cortex and report findings
      that point toward a modular distribution of pathological changes unique to each
      of these cortical types. We argue that changes in modular organization as seen in
      Alzheimer's disease are in all likelihood germane to the abnormal function of
      each cortical area. These changes at the modular level may lie at the heart of
      the devastating behavioral breakdown in this illness, which can be severe even
      with limited pathology.

PMID- 7505139
TI  - The genetics of myelin.
AB  - Myelin formation and maintenance requires complex interactions between neurons
      and glia, and between the integral protein and lipid components of the myelin
      sheath. Many of the underlying mechanisms may be examined by studying the
      perturbations caused by spontaneous and targeted mutations in myelin protein
      genes. This review summarizes the progress in our understanding of these
      mutations with an emphasis on integrating the recent advances in the genetics of
      myelin into a more generalized view of myelin organization and function.

PMID- 7505140
TI  - Specificities of IgE, IgG and IgA antibodies to ovalbumin. Comparison of binding
      activities to denatured ovalbumin or ovalbumin fragments of IgE antibodies with
      those of IgG or IgA antibodies.
AB  - We studied the binding activities of IgE, IgG and IgA antibodies in patients with
      allergy to hen's egg white against two different ovalbumin (OVA) preparations,
      which were physically or chemically denatured OVA and enzyme-digested OVA
      fragments. The binding activities of IgE antibodies to these OVA preparations
      with those of IgG or IgA antibodies were compared. It was found that the binding
      activities of IgE antibodies to denatured OVA by treatment with dithiothreitol,
      urea or hydrochloric acid were similar to those of IgG or IgA antibodies. In
      contrast, the binding activities of IgE antibodies to heat-denatured OVA or by
      treatment with sodium hydroxide at pH 11.0 were different from those of IgG or
      IgA antibodies to these denatured OVA. Furthermore, we found that the binding
      activities of anti-OVA antibodies in sera from patients with allergy to hen's egg
      white against fragmented OVA were different between IgE antibodies and IgG or IgA
      antibodies. Thus, it can be concluded that IgE antibodies to OVA in sera from
      patients with allergy to egg white differ from IgG or IgA antibodies in respect
      to binding activities against different preparations of denatured or fragmented
      OVA, probably due to differences in fine specificities of these antibodies
      against OVA.

PMID- 7505141
TI  - Variability of IgE-dependent histamine-releasing activity in supernatants of
      human mononuclear cells.
AB  - Histamine-releasing factors (HRF) that release mediators from human basophils by
      interacting with IgE have been identified from different cell sources, including
      lymphocytes, monocytes, thrombocytes and endothelial cells. These factors are
      studied in view of their potential importance as a stimulus in chronic
      inflammation. In this report we investigated the qualitative variability of the
      histamine-releasing activity in the supernatants of activated mononuclear cells.
      Purified human mononuclear cells of 8 donors were activated with
      streptokinase/streptodornase (SK/SD) and the supernatants (HRF-MN) were tested
      for histamine-releasing activity (HRA) in both allergic (RAST positive for
      inhalant allergens) and nonallergic individuals. Four of the eight HRF-MN
      supernatants were discriminating, i.e. showing no histamine-release response with
      nonallergic individuals, whereas four supernatants were not. Two of the HRF-MN
      supernatants that exhibited discriminating properties were studied in more
      detail. The response to HRF-MN was tested (1) in a direct bioassay on basophils
      of allergic (RAST positive for inhalant allergens) and nonallergic individuals
      and (2) in an indirect bioassay with 70% pure basophils of RAST-negative donors
      after passive sensitization with sera of allergic donors. An association was
      found between the response to HRF-MN and the RAST for inhalant allergens: none
      (0/12) of the RAST-negative but 15/22 of the RAST-positive individuals were HRF
      MN responders. The IgE dependency of HRF-MN was shown e.g. by inhibition of
      passive sensitization by preincubating a responder serum with monoclonal antibody
      (moAb) anti-IgE MH25-1. Our results are in contrast with findings of other
      investigators who use pooled supernatants and demonstrated HRF-MN responsiveness
      with both allergic and nonallergic donors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505142
TI  - Hepatitis C virus infection in type II essential mixed cryoglobulinemias.
AB  - The possible relationship between essential mixed cryoglobulinemias (EMCs) and
      hepatitis C virus (HCV) has been investigated in eight patients with type II EMCs
      and biochemical signs of liver damage, whose serum tested positive in the ELISA
      for anti-HCV. Sera were tested using the 2nd generation RIBA assay, while serum
      HCV-RNA was measured semiquantitatively by a RT-PCR in whole serum,
      cryoprecipitates and supernatants. In all patients a percutaneous liver biopsy
      and a bone marrow biopsy were performed. At liver biopsy, chronic active
      hepatitis and/or cirrhosis were present in 6 patients; in the remaining two, a
      lymphoplasmacytoid infiltration of elements positive for kappa light chains was
      found. In all patients a bone marrow biopsy showed a paratrabecular infiltration
      of monoclonal lymphoplasmacytoid elements similar to those found in the liver of
      the two patients described above. Antibodies against structural and non
      structural HCV proteins were detectable in the serum of all patients. HCV-RNA was
      amplified from the whole sera, cryoprecipitates and supernatants: significantly
      higher concentrations were found in cryoprecipitates than in supernatants. Our
      results confirm the high prevalence of HCV infection and ongoing viral
      replication in patients with type II EMC and suggest the possible implication of
      HCV in EMC pathogenesis.

PMID- 7505143
TI  - Detection of hepatitis B virus DNA by polymerase chain reaction in vaccinated and
      non-vaccinated Senegalese children.
AB  - An hepatitis B immunization programme was initiated in Senegal in 1978, and
      infants included in this controlled study have been followed for a period of 2-12
      years after immunization. During this period HBV infections have been observed
      both in vaccinated and non-vaccinated infants. The polymerase chain reaction was
      used to search for HBV DNA sequences in the sera of 153 children with evidence of
      serum markers of past or present HBV replication. Amplified HBV DNA sequences
      were detected in 93% of the HBsAg positive individuals, in 58% of those only
      positive for antiHBc antibodies and in 7.8% of antiHBs and antiHBc positive
      infants. The results confirm the high efficiency and long-lasting effectiveness
      of HB vaccine.

PMID- 7505144
TI  - Serum IgM antibodies to hepatitis C virus in acute and chronic hepatitis C.
AB  - A standardized commercially available immunoassay is not available for detection
      of IgM antibodies against hepatitis C virus antigens (IgM anti-HCV). Therefore,
      different "in-house" enzyme immunoassays have been assessed. These assays vary
      greatly in sensitivity, but specificity seems satisfactory in all of them. A
      typical IgM antibody response to HCV antigens is usually found in nearly all
      patients with acute hepatitis C. This antibody response rarely precedes the
      appearance of IgG anti-HCV, and it persists for a few months at high titer. Low
      titers of IgM anti-HCV are detectable in 50-80% of cases with chronic hepatitis
      C. IgM anti-HCV reactivity is typically found during acute exacerbation of
      chronic hepatitis C. Furthermore, many patients with chronic active hepatitis C
      without acute exacerbation also have IgM anti-HCV. In these patients a
      correlation exists between the titer of IgM anti-HCV and the biochemical
      parameters of liver disease. When alpha interferon therapy induces a sustained
      remission of liver disease activity, positivity for IgM anti-HCV disappears in
      more than 70% of cases. In contrast, patients who do not respond to therapy
      rarely loose IgM anti-HCV. In conclusion, serum IgM antibodies to HCV antigens
      are reliable markers of active HCV-induced liver disease both in acute and in
      chronic HCV infection.

PMID- 7505145
TI  - Hepatitis C virus infection in liver allograft recipients.
AB  - The impact of HCV infection after liver transplantation remains a topic of
      discussion. The aims of this study were to define the prevalence of anti-HCV
      antibodies in liver donors; the risk of acquired HCV infection and HCV re
      infection according to the pre-transplant anti-HCV status; the prevalence of HCV
      infection in post-transplant chronic hepatitis. Sera from 42 recipients with
      follow up longer than 6 months and their donors were tested for anti-HCV. By
      results at pre-transplant time patients were classified as follows: donor (D)
      negative and recipient (R) negative (D-/R-) 31; D-/R+ 9; D+/R- 1; D+/R+ 1. Twenty
      one patients with sustained hepatic dysfunction underwent liver biopsy. In group
      D-/R-, 5 patients showed anti-HCV positivity and 3 (9.7%) of them had acquired
      HCV hepatitis. In group D-/R+, 6 patients showed persistent anti-HCV positivity
      and 4 (44.4%) of them had recurrent HCV hepatitis; of these 2 died due to liver
      failure. The 2 patients of groups D+/R- and D+/R+ had normal liver function. Anti
      HCV negative hepatitis was found in 2 patients. The prevalence of anti-HCV
      positivity in liver donors appeared low (3.2%). Acquired HCV infection rate was
      9.7%. Pre-transplant HCV infection led to a high incidence of recurrence (44.4%).
      HCV was the major etiological agent in post-transplant chronic hepatitis (77.8%).

PMID- 7505146
TI  - Chromosome 9 short arm deletions in malignant diseases.
AB  - Deletions of 9p21-22, that frequently include the alpha-, beta- and omega-IFN
      gene cluster, are common in malignant diseases such as acute lymphocytic
      leukemia, malignant melanoma and malignant glioma. There is also evidence to
      support the role of a gene(s) on chromosome 9p21 in predisposition for familial
      malignant melanoma. Although initial studies implicated that the IFN genes could
      serve as tumor suppressor genes, there is now data, mainly based on estimations
      of minimum region of overlap for the deletions, indicating that the relevant
      tumor suppressor gene is located centromeric of the alpha-, beta-, omega-IFN gene
      cluster.

PMID- 7505147
TI  - A combination of granulocyte colony-stimulating factor and erythropoietin may
      synergistically improve the anaemia in patients with myelodysplastic syndromes.
AB  - In an attempt to obtain a synergistic effect on the hemoglobin levels in anaemic
      patients with myelodysplastic syndromes (MDS), granulocyte colony-stimulating
      factor (G-CSF) and erythropoietin (epo) were combined in a clinical phase II
      trial. Twenty-two patients with MDS were included in the study. G-CSF was given
      alone for six weeks and then in combination with epo for the following twelve
      weeks. Eight (38%) of 21 evaluable patients showed a significant increase in
      hemoglobin. One patient with a previous response and subsequent failure to epo
      alone improved after the addition of G-CSF. Responses were more frequent in
      patients with less advanced pancytopenia, lower endogenous levels of serum-epo
      and in those with ring sideroblasts in the bone marrow. The response frequency of
      38% is higher than in any study of epo as monotherapy. Moreover, patients with
      ring sideroblasts, who respond poorly to epo alone, showed a response rate of
      60%. Our findings suggest a synergistic in vivo effect of granulocyte-CSF and
      erythropoietin in patients with myelodysplastic syndromes.

PMID- 7505148
TI  - Cytotoxicity of a recombinant diphtheria toxin-granulocyte colony-stimulating
      factor fusion protein on human leukemic blast cells.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a potent stimulator of the
      growth of normal and malignant hematopoietic cells and synergizes with other
      factors such as interleukin-3 (IL-3) and granulocyte-macrophage colony
      stimulating factor (GM-CSF). The action of G-CSF is mediated through a specific
      membrane receptor, however it is not clear if all of the effects of G-CSF are
      direct or indirect. As a step towards addressing this problem, a recombinant
      diphtheria toxin (DT)-related human G-CSF fusion protein has been constructed and
      purified from E. coli. The 70,000 dalton chimeric protein has immunologic
      determinants characteristic of both DT and G-CSF. At high concentrations, DAB486
      G-CSF is cytotoxic towards G-CSF-dependent OCI/AML1 cells, but not factor
      independent OCI/AML3 cells; colony formation by G-CSF-responsive leukemic blasts
      from a patient with acute myeloblastic leukemia (AML) was also inhibited. The G
      CSF fusion toxin displayed ADP-ribosyltransferase activity in a cell-free system.
      Genetic conjugation of G-CSF to an enzymatically inactive DT mutant, CRM197,
      resulted in a 200-fold reduction in the ability of G-CSF to stimulate normal bone
      marrow colony formation. These results suggest that fusion of G-CSF to DT
      sequences interferes with some of the activity but not the specificity of the
      ligand binding domain of the molecule. Nevertheless, DAB486-G-CSF may be included
      with the increasing number of other toxin-hormone fusion proteins whose toxicity
      is directed towards specific receptor-bearing cells, and may represent a novel
      approach towards the study and treatment of leukemia.

PMID- 7505149
TI  - Long-term generation of colony-forming cells (CFC) from CD34+ human umbilical
      cord blood cells.
AB  - Human umbilical cord blood cells represent a potential alternative to bone marrow
      as a source of stem and progenitor cells for allogeneic transplantation.
      Therefore, many studies are underway to evaluate the number of cord blood stem
      cells and their amplification potential. We analyze here the amplification
      potential of CD34+ cord blood cells in liquid cultures stimulated with stem cell
      factor (SCF) in combination with interleukin-3 (IL-3), erythropoietin (Epo) or
      granulocyte colony-stimulating factor (G-CSF) under serum-deprived conditions. We
      report that under certain circumstances (stimulation with SCF and IL-3, replacing
      of the medium and growth factors every 3-4 days, no change of the initial culture
      flask, 37 degrees C as incubation temperature), CD34+ cells give rise to
      differentiated cells and progenitor cells for more than two months. During this
      period, more than 10(10) differentiated cells and 10(6) progenitor cells are
      generated from 0.25-1 x 10(4) CD34+ cells in the absence of a stromal layer.
      These data highlight the high proliferative and differentiative potential of cord
      blood stem cells and, because the culture procedures are relatively simple and do
      not require a stromal layer, open the way to the clinical use of ex vivo stem
      cell expansion.

PMID- 7505150
TI  - Retrovirus tests of human leukemia/lymphoma cell lines at DSM.
AB  - Permanently established human cell lines can produce several retroviruses. It is
      important to routinely test such cell lines for human T cell lymphotropic virus
      (HTLV) type I and II, and for human immunodeficiency virus (HIV) type 1 and 2 in
      order to exclude any potential biohazard from cell lines producing human
      retroviruses. Reverse transcriptase assay, polymerase chain reaction, and dot
      blot hybridization of in-vitro amplified DNA with virus-specific probes are used.

PMID- 7505151
TI  - New mutation of the myelin P0 gene in a pedigree of Charcot-Marie-Tooth
      neuropathy 1.
AB  - P0, the major structural protein of peripheral myelin, is a homophilic adhesion
      molecule with a single immunoglobulin (Ig) domain, which contains a single N
      linked glycosylation site and two cysteines. We have previously reported four
      different mutations of the myelin P0 gene in four families of Charcot-Marie-Tooth
      neuropathy type 1 (CMT1). In this study we found a new mutation of the myelin P0
      gene in a small family of CMT1. The affected persons had an A - to - G
      substitution of nucleotide 245 of the myelin P0 gene in one allele, leading to a
      cysteine substitution for tyrosine82 in the extracellular Ig-domain. An
      additional cysteine in the extracellular domain may form a disulfide bond and
      cause an inappropriate change in the tertiary structure of the functional Ig
      domain of P0.

PMID- 7505152
TI  - Identification of an mRNA species which encodes a voltage-operated Ca2+ channel
      in rat liver mRNA.
AB  - cDNA which encodes part of the alpha 1-subunit of the rabbit skeletal muscle L
      type voltage-operated Ca2+ channel (VOCC cDNA) was employed to search for the
      presence in whole liver and hepatocytes of poly (A+) RNA homologous to mRNA which
      encodes VOCCs. Such homologous mRNA would be a candidate for mRNA which encodes
      the putative hepatocyte receptor-activated Ca2+ inflow system (RACIS). Northern
      blot analysis showed that poly (A+) RNA prepared from intact liver tissue, but
      not hepatocytes, contained a poly (A+) RNA species comparable in size to that
      which encodes the alpha 1-subunit of the L-type VOCC. It is concluded (a) that
      hepatocytes do not possess VOCCs or that the levels of VOCC poly(A+) RNA in
      hepatocytes are too low to be detected by Northern analysis and (b) that another
      cell type present in liver tissue does possess a VOCC. In a low stringency screen
      of a rat liver cDNA library employing VOCC cDNA as a probe, seven positive cDNA
      clones were obtained. While regions of the 2.3 kb cDNA insert from one of these
      clones showed sequence similarities with regions of VOCC cDNA, the 2.3 kb
      sequence did not appear to encode a Ca2+ channel. The present results suggest
      that the approach of low stringency cDNA library screening is unlikely to allow
      isolation of RACIS cDNA.

PMID- 7505153
TI  - The effect of boron on plasma membrane electron transport and associated proton
      secretion by cultured carrot cells.
AB  - Plasma membrane electron transport reactions and associated proton secretion were
      studied in boron-deficient carrot cells. It was found that the hormone-sensitive
      plasma membrane NADH oxidase was inhibited by boron deficiency and that under
      such conditions activity could be restored by exogenous boric acid with or
      without 2,4-dichlorophenoxy acetic acid. Gramicidin, a channel-forming
      protonophore, further stimulated NADH oxidase by carrot cells. Proton secretion,
      associated with plasma membrane H(+)-ATPase, was also affected by boron
      deficiency, but not as severely as ferricyanide-generated proton secretion,
      reflecting plasma membrane electron transport. The addition of 1 mM boric acid
      and 1 microM 2,4-dichlorophenoxy acetic acid to carrot cells fully restored the
      H+ secretion in presence of ferricyanide. The effect of boron deficiency in
      cultured carrot cells can, therefore, be directly associated with cell growth
      through its effect on the plasma membrane NADH oxidase and H+ secretion.
      Ferricyanide provides a probe which activates transmembrane electron transport
      that is only coupled to proton release when boron is present.

PMID- 7505154
TI  - The DA6-147 monoclonal antibody raised against the HLA-DR alpha chain identifies
      a cryptic epitope on the BoLA-DR alpha chain.
AB  - By combining immunoprecipitation of BoLA molecules with monoclonal antibodies
      raised against 2 different major histocompatibility class II antigens, TH14B and
      TH81A, and western blotting using the anti-HLA DR alpha monoclonal antibody DA6
      147, we characterized an epitope conserved on BoLA- and HLA-DR alpha chains. This
      epitope, not accessible on intact cells, was revealed after cell lysis. In
      addition, these results allowed us to define TH14B as an anti-BoLA-DR monoclonal
      antibody whereas TH81A, raised against the products of a second MHC locus, is
      probably an anti-BoLA-DQ monoclonal antibody.

PMID- 7505155
TI  - New visions for medical-surgical nursing.

PMID- 7505156
TI  - A time for action.

PMID- 7505157
TI  - Galaninergic innervation of the cholinergic vertical limb of the diagonal band
      (Ch2) and bed nucleus of the stria terminalis in aging, Alzheimer's disease and
      Down's syndrome.
AB  - The galanin (GAL) containing peptide fiber system circuit which innervates
      acetylcholine containing basal forebrain neurons has been shown to hypertrophy
      and hyperinnervate remaining cholinergic Ch4 perikarya in Alzheimer's disease
      (AD). The present study examined whether a similar hyperinnervation occurs within
      the cholinergic vertical limb of the diagonal band nucleus (Ch2), a portion of
      the basal forebrain which, unlike Ch4, exhibits only modest degeneration in AD.
      Furthermore, we evaluated whether GAL hyperinnervation occurs within the basal
      forebrain in Down's syndrome, a genetic disorder with extensive AD-like pathology
      including cholinergic basal forebrain neuron degeneration. The present study
      revealed that virtually all Ch2 neurons were GAL immunonegative. However, this
      region was innervated by GAL immunoreactive (ir) interneurons and fibers
      associated with a major galaninergic pathway which travels through the substantia
      innominata enroute to the hypothalamus, bed nucleus of the stria terminalis as
      well as vertical limb of diagonal band nucleus. GAL-ir fibers coursing within
      this fiber bundle hypertrophied in AD relative to age matched controls and the
      Down's cases. Within the putative Ch2 terminal zones in AD, many of the remaining
      cholinergic neurons were hyperinnervated by GAL despite the modest reduction in
      Ch2 neurons. In contrast, GAL-ir fibers were not hypertrophied in Down's syndrome
      despite extensive cholinergic cell loss within Ch4. Taken together these findings
      suggest that extensive cholinergic basal forebrain cell loss alone is not
      sufficient to trigger the basal forebrain GAL plasticity response found in AD.

PMID- 7505158
TI  - Dendritic atrophy and remodeling of amygdaloid neurons in Alzheimer's disease.
AB  - The current study examined changes in the dendritic arbor of basolateral
      amygdaloid neurons in Alzheimer's disease (AD). Quantitative analysis of Golgi
      Kopsch-impregnated tissue samples revealed a significant reduction in the total
      dendritic length per neuron in AD. Terminal and nonterminal dendritic segments
      were affected similarly. Somatofugal ordering of the same segments, however,
      indicated that the reductions were restricted to the inner portion of the
      dendritic tree, coupled with significant AD-related increases in the length and
      number of the highest order segments. These data suggest that despite an overall
      AD-related loss of dendritic length in this amygdaloid subregion, new dendritic
      segments continue to form. The loss of proximal segments, combined with the gain
      of distal segments, may be interpreted as dendritic remodeling in the course of
      the disorder.

PMID- 7505159
TI  - Anxiety, knowledge and satisfaction in women receiving false positive results on
      routine prenatal screening: a randomized controlled trial.
AB  - The majority of women receiving an abnormal result on routine prenatal screening
      subsequently give birth to unaffected children. Previous studies have documented
      high levels of anxiety in women receiving such false positive results. In an
      attempt to reduce this anxiety, two methods of preparing women for undergoing
      such testing were compared: provision of detailed written information about
      maternal-serum alpha-fetoprotein testing; and anxiety management training.
      Eligible women were randomly allocated to one of five groups. Eighty-five women
      subsequently received false positive results on routine alpha-fetoprotein
      testing. There was some evidence that completing the study questionnaires had an
      anxiety-reducing effect. In contrast with the results of previous studies, there
      was no evidence that receipt of an abnormal alpha-fetoprotein result resulted in
      raised anxiety. Neither of the interventions, alone or in combination, had an
      effect upon anxiety following an abnormal alpha-fetoprotein result. Receipt of
      detailed written information however, led to women having more knowledge and
      being more satisfied with the amount of information that they had. One in three
      of the class groups reported that the classes had influenced the way they had
      dealt with worries. Although the interventions did not reduce anxiety in this
      study, there are other reasons for considering their incorporation into routine
      clinical practice.

PMID- 7505160
TI  - Urinary trypsin inhibitory activity: not a useful test for detecting bacterial
      infections in elderly people.

PMID- 7505161
TI  - Usefulness of urinary trypsin inhibitory activity in the elderly: possible
      explanations for conflicting results.

PMID- 7505162
TI  - Prevalence of antibodies to hepatitis C virus in intravenous drug addicts.

PMID- 7505164
TI  - Zonal organization within the projection from the inferior olive to the rostral
      paramedian lobule of the cat cerebellum.
AB  - The projection from the inferior olivary nucleus to the forelimb-related regions
      of the c1, c2 and c3 zones within rostral folia of the paramedian lobule of the
      cat cerebellum was studied using a combined electrophysiological and
      neuroanatomical tracing technique. In each experiment, the cerebellar cortical
      zones were identified by their receipt of spino-olivocerebellar input evoked by
      percutaneous electrical stimulation of the limbs. A small (15-30 nl) injection of
      wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) was then made into the
      centre of one of the zones. The olivary regions projecting to each zone were
      compared with the regions within the olive that have previously been shown to
      project to the corresponding cortical zones within lobule V of the anterior lobe.
      The results show that some (but not all) of the paravermal zones in the anterior
      lobe are also represented in the paramedian lobule (PML). The most medial (c1)
      zone in rostral PML receives climbing fibre input from an area in the rostral
      dorsal accessory olive which overlaps partially with the area that projects to
      the medial half of the c1 zone in lobule V. A zone equivalent to the lateral half
      of the c1 zone (the cx zone) in lobule V does not appear to be present within
      rostral PML. A middle (c2) zone within rostral PML receives olivary input from a
      region within the rostral medial accessory olive that overlaps partially with the
      area that projects to the c2 zone in lobule V. The presence of a c3 zone within
      rostral PML was found to be variable between animals and it could be identified
      electrophysiologically in only two out of a possible nine cases. In summary, the
      results demonstrate that, although a number of similarities exist between the
      olivocerebellar projections to corresponding cortical zones in the two forelimb
      receiving regions of the cat paravermal cortex, the differences in
      olivocerebellar connectivity between the two regions suggest that functional
      differences between them may also exist.

PMID- 7505163
TI  - Training chicks on a passive avoidance task modulates glutamate-stimulated
      inositol phosphate accumulation.
AB  - The effects of glutamate, N-methyl-D-aspartate (NMDA), (+)-5-methyl-10,11-dihydro
      5H-dibenzo-(a,d)-cyclo-hepten 5,10-imine maleate (MK801), alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionate (AMPA) and quisqualate on the accumulation of
      inositol phosphates (IP) from the breakdown of phosphoinositides in vitro have
      been studied in tissue prisms derived from a region of the chick forebrain, the
      intermediate medial hyperstriatum ventrale (IMHV). In prisms from the left IMHV,
      glutamate stimulated IP accumulation by 10-20%, AMPA by 55% and quisqualate by
      650%. These effects were more marked in the right IMHV, where AMPA stimulated IP
      accumulation by 157% and quisqualate by 920%. MK801 and NMDA had no significant
      effect on IP accumulation in either hemisphere. The left IMHV is known to be the
      site of a biochemical cascade resulting in synaptic remodelling following
      training day-old chicks on a one-trial passive avoidance task. The effect of such
      training was to reduce glutamate-stimulated accumulation of IP by 27% (P < 0.05)
      in prisms taken 30 min after training. There was no effect on prisms taken at 5
      or 180 min after training, and no effect at any time in the right IMHV. MK801,
      injected intraperitoneally before training at a concentration known to produce
      amnesia for the passive avoidance task, abolished the training-induced decrease
      without itself affecting IP accumulation. Taken in conjunction with
      pharmacological and autoradiographic evidence, these results indicate that memory
      formation for the passive avoidance task involves the activation of NMDA receptor
      channels, but not quisqualate or AMPA receptors, in the left IMHV of the chick 30
      min after training.

PMID- 7505165
TI  - Single-channel activity in cultured cortical neurons of the rat in the presence
      of a toxic dose of glutamate.
AB  - Rat cortical neurons grown in cell culture were exposed to 500 microM glutamate
      for 5 min during continuous current recording from cell-attached patches. The
      Ca(2+-dependence and ion selectivity of the membrane channels activated during
      and after glutamate application were studied in inside-out patches. Glutamate
      blocked spontaneous action potential firing. In 77% of the experiments glutamate
      activated several types of ion channels indirectly, i.e. via a change of
      cytoplasmic factors. Channel activity did not disappear after removing glutamate
      from the bath. A K+ channel requiring intracellular calcium ([Ca2+]i) was
      activated in 44% of the experiments (conductance for inward currents in cell
      attached patches 118 +/- 6 pS; 'BK channel'). Another Ca(2+)-dependent channel
      permeable for Cl- (conductance for outward currents in cell-attached patches 72
      +/- 17 pS), acetate and methanesulphonate appeared in 26% of the patches. Other
      K+ channels of smaller conductance were infrequently observed. During and after
      glutamate application the activity of the BK channel showed an initial increase
      followed by a transient decay and a second rise to a plateau, probably reflecting
      a similar time course of changes in [Ca2+]i. Both phases of increasing channel
      activity required the presence of extracellular Ca2+ suggesting that [Ca2+]i was
      mainly increased by Ca2+ influx. The N-methyl-D-aspartate (NMDA) antagonists
      dizocilpine (MK-801, 10 microM) and DL-2-amino-5-phosphonovaleric acid (AP5; 100
      microM), added within 5 min after glutamate application, stopped BK channel
      activity and restored the spontaneous action potential firing. We conclude that
      the influx of Ca2+ through NMDA receptor channels causes a strong activation of
      Ca(2+)-dependent K+ channels, which is likely to result in pronounced loss of
      intracellular K+. NMDA receptor channels seem to remain active for a long time (>
      10 min) after the end of glutamate application.

PMID- 7505166
TI  - The development of retinal ganglion cell decussation patterns in postnatal
      pigmented and albino ferrets.
AB  - The decussation patterns of retinal ganglion cells in postnatal pigmented and
      albino ferrets were examined by using retrograde axonal tracers. Following
      unilateral injections into the optic pathway of newborn pigmented ferrets,
      approximately 13,000 cells were labelled in the ipsilateral retina. The majority
      (11,500) of these were located in temporal retina. Postnatally, the numbers of
      cells projecting ipsilaterally from temporal retina fell by 49%. High rates of
      loss were observed in both the smaller uncrossed projection from nasal retina
      (92%) and also in the crossed projection from temporal retina (84%). After
      injections on the day of birth, a decussation line was not obvious in the crossed
      projection: > or = 14,000 labelled cells were found in temporal retina. Double
      tracer studies showed that very few of these cells had axons which projected
      bilaterally. The numbers of ipsilaterally projecting cells labelled in neonatal
      albino ferrets was dramatically reduced. Only approximately 2500 were labelled in
      temporal retina following injections at birth. As in pigmented ferrets, about
      half of these cells subsequently died. The reduced uncrossed projection in albino
      neonates was associated with an increase in the crossed projection from temporal
      retina, in which approximately 21,000 cells were labelled following injections at
      birth. These results suggest that differential postnatal ganglion cell death
      establishes the adult decussation pattern in the contralateral retinal projection
      but merely refines the pattern already established in the uncrossed projection.
      Postnatal ganglion cell death plays no significant role in generating the
      abnormal projections found in albino ferrets.

PMID- 7505167
TI  - The neurotrophins BDNF, NT-3 and NT-4/5, but not NGF, up-regulate the cholinergic
      phenotype of developing motor neurons.
AB  - Although developing motor neurons express low-affinity nerve growth factor (NGF)
      receptors, there is no known biological effect of NGF on developing or adult
      motor neurons. In this study, we found that, unlike NGF, brain-derived
      neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5)
      stimulated cholinergic phenotype by increasing choline acetyltransferase (CAT)
      activity in cultures enriched with embryonic rat motor neurons. Ciliary
      neurotrophic factor (CNTF) also stimulated CAT activity. The effects of BDNF and
      NT-4/5 on CAT activity appeared to be synergistic with that of CNTF. Cotreatment
      with BDNF and NT-3 resulted in an additive effect, suggesting that signal
      transduction was mediated through different high-affinity receptors tyrosine
      kinases B and C (Trk B and Trk C). However, cotreatment with BDNF and NT-4/5 did
      not result in an increase in CAT activity greater than that of either BDNF or NT
      4/5 alone, suggesting that their effects were mediated via the same receptor Trk
      B. Supporting our findings that spinal cholinergic neurons are responsive to
      trophic actions of members of the neurotrophin family, motor neuron-enriched
      cultures were found to express mRNA for Trk B and Trk C, which have been
      identified as high-affinity receptors for BDNF and NT-4/5, and NT-3,
      respectively.

PMID- 7505168
TI  - The proximal region of the MBP gene promoter is sufficient to induce
      oligodendroglial-specific expression in transgenic mice.
AB  - To characterize regulatory DNA sequences involved in oligodendroglial expression
      of myelin basic protein (MBP), transgenic mice carrying a 256 bp fragment of the
      mouse MBP promoter fused to an Escherichia coli lacZ gene were generated. Of four
      transgenic families, two (lines 2 and 4) expressed beta-galactosidase activity in
      the nervous system but not in most other tissues. Histochemical and
      immunohistochemical analysis of adult brain from these two lines showed
      oligodendroglial-specific expression of the transgene. In line 2, only a small
      proportion of oligodendrocytes expressed the transgene, and in labelled cells the
      product of the enzymatic reaction with beta-galactosidase was confined to a small
      round vesicle in the vicinity of the nucleus. In contrast, in tissue sections
      from line 4 adult brain and spinal cord beta-galactosidase activity was much more
      intense and at least 80-90% of oligodendrocytes expressed the transgene.
      Detection of the MBP-lacZ transcript by in situ hybridization showed that the
      transgene mRNA was confined to the oligodendrocyte cell body. These results
      suggest that cis-acting regulatory elements, specifying oligodendrocytes
      identity, are located within 256 bp upstream from the MBP gene.

PMID- 7505169
TI  - Characteristics of clients referred to home, hospice and hospital palliative care
      services in Western Australia.
AB  - Perth, in Western Australia, has three major palliative care services: a home
      care service, a freestanding hospice and a purpose-built palliative care unit in
      a teaching hospital. A retrospective study of patients referred to these services
      over a six-month period was carried out to find how they were used. The records
      of 176 clients were compared, which showed that there were some differences
      between the client groups referred to each of the services. Those referred to the
      inpatient services were older (F = 0.0031), less likely to have a carer available
      (chi 2 = 18.62, p < 0.5) and needed more nursing care. Lung cancer accounted for
      more male admissions (29%) to all services, while breast and lung cancer were
      more common among women, with a mixed pattern of referral. Lack of private
      insurance did not seem to influence the choice of service. Overall the clients of
      the inpatient services were older, had more nursing needs and were less likely to
      have someone to care for them, characteristics which health services facing an
      ageing population need to consider.

PMID- 7505170
TI  - Domiciliary care: a comparison of the views of terminally ill patients and their
      family caregivers.
AB  - This study compares terminally ill patients and their family caregivers in terms
      of the physical and emotional status of the patients, the adequacy of the support
      provided for the patients and where the patients would be most appropriately
      placed during the last stage of their lives. Patients and caregivers shared
      similar views about the latter, but there was a lack of concordance between them
      regarding the patients' physical and emotional state. Patients generally reported
      a much more favourable view of their outlook and emotional state than did their
      caregivers. Caregivers may need help to review their assumptions about the
      patients' emotional welfare, and caution should be used in accepting caregivers'
      views about how patients are coping emotionally.

PMID- 7505171
TI  - General practitioners and palliative care.
AB  - A randomly selected sample of 158 South Australian general practitioners (GPs)
      were sent a questionnaire which assessed opinions and management practices in the
      palliative care of terminally ill patients. A total of 117 responses (74%) were
      received. Most GPs were at least moderately satisfied with the care they were
      able to give their terminally ill patients, although a substantial number
      reported difficulties in pain and other symptom control, dealing with relatives'
      emotional distress and attending to patients' psychosocial needs. There was
      considerable support for continuing education in these aspects of palliative
      care. More than half were at least somewhat concerned by opioid side effects and
      impairment of cognitive function, although opioid dependence was not a concern.
      Considerable dissatisfaction was expressed with public hospital care for the
      terminally ill and most felt excluded from decision-making once their patients
      were admitted. The findings suggest that continuing education is required for GPs
      and that palliative care should become an integral part of undergraduate
      education. There is also a need to enhance communication and co-ordination
      between hospital and community-based services for the terminally ill.

PMID- 7505172
TI  - Should hospices offer respite admissions to patients with motor neurone disease?
AB  - The provision of inpatient respite care for patients with motor neurone disease
      (MND) in hospices is variable. Some institutions are concerned about accepting
      patients who may need long-term care. Some see 'respite' care as simply a short
      residential stay with little nursing or medical input being necessary. Others,
      however, feel that respite offers the potential for palliative care and should be
      provided within the spectrum of a hospice service. This retrospective study
      examines that group of MND patients requesting respite care in terms of
      demographic details, problems identified and medical and nursing interventions
      made during respite admissions. The results indicate a great need for symptom
      management in these patients as well as co-ordination of future community care.
      Most patients were discharged home after respite admissions and the median stay
      in the hospice (15 days) was identical to that of cancer patients. We conclude
      that respite admissions to the hospice were valuable both for MND patients and
      their carers. Units not currently involved in this work may wish to reconsider
      their position.

PMID- 7505173
TI  - Diabetes mellitus in hospice patients: some guidelines.
AB  - Diabetes is a relatively common medical condition in hospice patients. Management
      should be aimed at maintaining quality of life and the views of patients and
      families should be taken into consideration.

PMID- 7505175
TI  - Palliative care programmes in Latin America.

PMID- 7505174
TI  - Specialist medical education and training in palliative care.

PMID- 7505176
TI  - Chemotherapy in spinal cord compression.

PMID- 7505177
TI  - The organization of hospital-based home care for terminally ill cancer patients:
      the Motala model.
AB  - In 1977, the first palliative home care programme in Sweden, the Motala hospital
      based home care, was established to provide a high level of medical care on a 24
      hour basis, as an alternative and a replacement to hospital care. The current
      study summarizes the care and organizational needs of 179 consecutive terminally
      ill cancer patients treated during a 10-year period. Of the patients, 70% came
      from acute clinics. The median time of care was 36 days. The need for help with
      activities of daily living was a significant predictor of the length of survival,
      with the greatest difference between four or less compared to five or six items
      (p = 0.0006). Analgesics were needed by 96% of the patients, and 78% were
      provided with various facilities such as hospital beds. The input of family
      members as primary caregivers was essential for successful care, as were security
      factors such as easy availability of a nurse or doctor, at any time day or night,
      and an immediate, guaranteed hospital bed, if needed. As many as 89% of the
      patients who wished to live at home until death actually did so. We conclude that
      hospital-based home care according to the Motala model can replace hospital care
      for selected patients, but only if both the patient and the family approve.

PMID- 7505178
TI  - Research and palliative care: the pursuit of reliable knowledge.

PMID- 7505179
TI  - The concept of hope and the will to live.
AB  - Hope is defined as a concept that suggests a greater emotional component than
      mere expectation, and is seen as an active process of conscious and unconscious
      reasoning. Hope is intrinsically linked with caring, and the professional role of
      the nurse can often influence the generation of hope or hopelessness in the care
      of patients. The appropriateness of removing all hope even within palliative care
      is questioned. A case study is presented in which a patient, requesting
      euthanasia, hovered on the brink of death yet would not die. For this patient all
      'hope' of wanting to live had waned, yet she could not die. A new concept of
      'rational no-hope' is postulated.

PMID- 7505180
TI  - Euthanasia: the word and the act in palliative medicine.
AB  - The word 'euthanasia' has been used with a variety of meanings, all of which
      refer to one precise action: the killing of a suffering person. A moral
      evaluation of such an act can lead us either to condemn it a priori, shutting the
      door upon any argument, or to allow further discussion. But the issue must be
      discussed, starting with an analysis of the meaning of the word and then
      examining both whether it is justifiable or not in palliative care, and whether
      it is acceptable within a general medical context. This paper supports the
      assumption that a correct and clear-cut analysis of the word euthanasia and of
      the act to which the word refers can be carried out only through a debate which
      separates the various levels of reasoning (medical, ethical, religious,
      political, legal) and keeps distinct from one another.

PMID- 7505181
TI  - Two lawyers and a technician.
AB  - The major arguments used to support the legalization of euthanasia are that such
      a move would increase autonomy both for individuals and for society as a whole,
      and would diminish suffering. This paper examines these two points from several
      angles, and concludes that, from the standpoint of society as a whole, the
      legalization of euthanasia would be likely to achieve the complete opposite: a
      reduction in autonomy and an increase in overall suffering. The involvement of
      doctors in euthanasia is seen as a separate debate. The medical ethic of
      beneficence and its importance are discussed, together with the consequent
      dilemmas produced if this ethic is to be retained at the same time as requesting
      doctors to perform euthanasia. Consequences for the doctor-patient relationship
      in terms of loss of trust are described. To resolve these dilemmas it is
      suggested that, if euthanasia were legalized, initial assessment should be by two
      lawyers, and the act itself performed by a technician, suitably vocationally
      trained.

PMID- 7505182
TI  - Audit of neural blockade for palliative care patients in an acute unit.
AB  - During the period from September 1990 to March 1992, 155 nerve blocks were
      performed for 125 patients as part of the clinical management of pain due to
      malignant disease. The efficacy, in terms of pain score reduction, and
      spontaneously reported side effects secondary to these procedures were
      prospectively audited. Neural blockade was undertaken in accordance with strict
      clinical criteria, and medication was optimized with the aim of achieving maximum
      analgesia with minimum side effects at all times. Pain was assessed before the
      block, 24 hours after the block and at follow-up (two to six weeks) using visual
      analogue scores or verbal rating scales. All patients were audited. The total
      (all patients, all blocks) median (lower-upper quartile) pain score dropped from
      8 (6-10) cm before the block to 2 (0-4) cm at 24 hours after the block (p < 0.05)
      and to 1 (0-4) cm at follow-up (p < 0.005). A concomitant reduction in analgesic
      requirements was observed. The incidence of serious side effects was low (two
      patients in this series). The results indicate the usefulness of these techniques
      for patients in the palliative care setting.

PMID- 7505183
TI  - Validity of the support team assessment schedule: do staffs' ratings reflect
      those made by patients or their families?
AB  - This study aimed to assess the validity of the Support Team Assessment Schedule
      (STAS), a measure of the outcome of palliative care, through comparisons with the
      views of patients and family members. STAS ratings completed by two support teams
      were compared with (1) patients' ratings and (2) family member/carer ratings of
      seven (of the total 17 STAS) items, collected by independent interviewers. Of 183
      patients referred to the teams, 84 (46%) were interviewed and 99 (54%) could not
      be contacted. Sixty-seven patients had family members or carers, all of whom were
      interviewed. Tests for agreement between team and patient were high for four
      items, and showed moderate correlations (Spearman's rho ranged 0.45-0.66) for
      five items, excepting two items including family needs. The summed scores for
      seven items were correlated, rho = 0.66, p < 0.0001. Where differences were
      found, team members identified more problems than patients' self-ratings, except
      for one item, 'pain control', where team members identified fewer problems. Team
      ratings were usually closer to those of the patients than to those of the family
      member; a team rating often lay between the patient's and family member's rating.
      The STAS is a measure of professional assessment which is independent from,
      although based on, the patient and family. The results support the validity of
      STAS as a measure of the outcome of palliative care from the perspective of a
      palliative care team.

PMID- 7505184
TI  - Survivor focus groups: a quality assurance technique.
AB  - The use of a total quality management frame work by the palliative care team
      (PCT) at the Chedoke-McMaster hospitals has led to a standardized method of
      obtaining feedback from some of the hospitals' customers. Every three months, a
      focus group is convened of randomly chosen significant others who were most
      involved in a nonprofessional caregiving role for the deceased patients. The
      participants are invited to discuss their perceptions of the quality of care
      provided by the PCT and how it could be improved. This paper describes the
      procedures used and feedback received in the first year of this audit procedure.
      The lessons learned during implementation of this audit procedure and how this
      feedback has affected the PCT's functioning are discussed. This process can
      provide information for continuous improvement of the care provided by the PCT.

PMID- 7505185
TI  - Palliative medicine--a time for definition?

PMID- 7505186
TI  - Hormone treatments in the common 'hormone-dependent' carcinomas.
AB  - Current understanding of the mechanisms of action of hormonal therapies in
      carcinomas of the breast, prostate, endometrium and ovary is briefly reviewed.
      The range of available hormonal therapies for each disease is considered together
      with response rates, toxicity and any evidence for survival benefit. Practical
      guidelines for the palliative use of hormonal therapies are suggested.

PMID- 7505187
TI  - Octreotide in relieving gastrointestinal symptoms due to bowel obstruction.
AB  - Gastrointestinal obstruction is a common problem in advanced malignant disease,
      but its management remains controversial. In those patients for whom surgery is
      not appropriate, medical intervention is the only remaining option. We present a
      series of 14 patients with intestinal obstruction who were managed with
      subcutaneous injections of octreotide, a somatostatin analogue which reduces the
      volume of gastrointestinal secretions. Good control of vomiting was achieved in
      12 patients, and no major side effects were observed. Octreotide would appear to
      be a useful drug in this clinical situation.

PMID- 7505188
TI  - Palliative home care and place of death among cancer patients: a population-based
      study.
AB  - This population-based study of all cancer deaths (n = 12,343) occurring in Genoa,
      Italy, from 1986 to 1990 investigated the relation between place of death and
      age, sex, marital status, education, cancer site and provision of palliative home
      care (PHC). The proportion of home deaths significantly increased from 27.9%
      (1986) to 33.0% (1990) and was twice as frequent among PHC users (60.8%) than
      among nonusers (29.3%). The number of patients dying of cancer who received PHC
      increased from 41 in 1986 (1.6% of cancer deaths) to 191 in 1990 (8.0% of cancer
      deaths). PHC users, when compared to nonusers were younger, more frequently
      married, had a higher level of education and were more frequently affected by
      cancers of the lung, breast or prostate. Multivariate analysis shows that the
      probability of home death increased with increasing age and education level and
      was higher in females and in married patients. The provision of PHC was the
      strongest predictor of home death (OR = 4.00; 95% CI = 3.33-4.81), while the
      temporal trend almost disappeared. These results suggest that most of the
      increase in home deaths from 1986 to 1990 is attributable to the PHC and that
      expansion of the PHC services may enable about 60% of cancer patients to die at
      home. These results appear to be desirable from the individual patient's
      viewpoint and in a public health perspective.

PMID- 7505189
TI  - Longitudinal observations on normal and abnormal voiding in men over the age of
      50 years.
AB  - A cohort of 200 men over the age of 50 years was selected at random. Initially
      112 men participated. After 5 years 61 were participating, and 2 years later 34
      men still had no voiding problems, while 19 had had treatment for prostatism. A
      history was obtained and all 112 had symptom analysis and uroflow examination.
      The uroflow variables Qmax, Qave, Qmax-time, Q "corrected", volume and the ratio
      Qmax/Qmax-time were recorded together with the symptom score and subjective
      evaluation. After 5 and 7 years all primary data were reviewed in the 61 and 34
      men respectively, while a full history was obtained in the rest. The 3 sets of
      data were evaluated separately as 3 cross-sectional investigations and as paired
      data sets by means of non-parametrical statistical analysis. Comparing the 3 sets
      of data longitudinally, significant differences were found in Qmax, Qave, Qcor
      and Acc. A correlation analysis showed that Qmax, Qave, Q "corrected" and volume
      decreases significantly with advancing age in asymptomatic men, while no
      correlation with age was found in the 19 treated men. On the basis of the 93 men,
      untreated for 7 years, nomograms of Qmax, Volume and Acc were constructed using
      2.5, 25, 50, 75 and 97.5% percentiles in 5-year groups. Likewise, a nomogram on
      symptom score was constructed on the basis of the 82 men, asymptomatic and
      untreated for 7 years. In conclusion, uroflow in subjectively normal men over the
      age of 50 years shows increasing abnormality with advancing age. At the same time
      elderly men tolerate a considerable amount of symptoms of infravesical
      obstruction. The severity of symptoms increased with advancing age, but
      differently in persons likely and not likely to need operation.

PMID- 7505190
TI  - Quantitation of potentially undiagnosed incidental carcinoma of the prostate in
      patients treated non-surgically for benign prostatic hyperplasia.
AB  - Prostatectomy is the standard treatment for benign prostatic hyperplasia (BPH)
      and non-surgical treatment of prostatism would reduce the detection of Stage A
      prostate cancer. We wished to identify the number of potentially undiagnosed
      cancers resulting if non-surgical therapy were used to treat a presenting
      complaint of BPH. We also sought to identify the age group which would most
      clearly benefit from treatment of Stage A prostate cancer. Our series of
      transurethral prostatectomy specimens showed 92/996 patients (9.2%) positive for
      incidental carcinoma; 26/92 patients (28%) received further treatment and 25 of
      the 26 patients had Stage A2 disease. After evaluating life-tables and survival
      data on untreated A2 disease, the population aged < or = 72 years had a relative
      benefit of treatment ratio > 1.0, i.e. had a greater likelihood of dying from
      prostate cancer than from natural causes; 17/616 (2.8%) of the population aged <
      72 years had their A2 disease treated and would have potentially been denied
      early cancer treatment if non-surgical management of BPH had been employed. The
      above figures assume 100% non-surgical treatment of BPH and no screening for
      prostate cancer pre-treatment. Stage A2 patients in this study demonstrated no
      significant difference in cause-specific survival rates between treated and
      untreated study groups (both 0%) or between treated study patients and untreated
      historical patients. Treated A2 patients demonstrated a significantly lower 5
      year progression rate (0 vs 32%) relative to untreated patients reported in the
      literature, and a trend toward a significantly lower progression rate (0 vs 25%)
      relative to untreated study patients.

PMID- 7505191
TI  - Analysis of biopsy findings and implant quality following ultrasonically-guided
      125I implantation for localised prostatic carcinoma.
AB  - Transperineal ultrasound-guided 125I implantation was undertaken in 52 patients
      with localised prostate cancer. After implantation, ultrasound-guided biopsies
      were taken from the previous malignant areas every 6 months in all patients. The
      percentage of negative biopsies increased from 22% at 6 months to 50% at 48
      months. Implant quality was analysed in 37 patients. The difference between
      isodose levels encompassing the prostate and the aimed levels of 160 Gy was taken
      as a measure of implant quality. A good quality implant (< 10% underdosage) was
      found in 43% of patients, a moderate quality (10-25% underdosage) in 35%, and a
      poor quality implant (> 25% underdosage) in 22%. A statistically significant
      correlation was found between the quality of the implant and resulting negative
      biopsy at the original tumour site. Determination of prostate specific antigen
      (PSA) was not possible from the beginning of the study but an analysis with
      biopsy findings, implant quality and prostate volume reduction during follow-up
      has been performed since 1989. A significant correlation was observed between
      implant quality and serum PSA, and also between volume reduction and serum PSA.

PMID- 7505192
TI  - Re-evaluation of the need for pelvic lymphadenectomy in low grade prostate
      cancer.
AB  - In a series of 166 patients undergoing radical prostatectomy and bilateral pelvic
      lymph node dissection for clinical stage A and B prostate cancer we found that
      83% of patients with lymph node metastases had a final tumour Gleason score > or
      = 7. Gleason scoring of the pre-operative biopsy demonstrated 3 groups of
      patients with biopsy scores < or = 5, 6, and > or = 7, and a prevalence of lymph
      node metastases of 2, 13 and 23% respectively. The pre-operative serum prostate
      specific antigen (PSA) was of marginal value in predicting either the presence of
      lymph node metastases or the presence of cancer, since 15% of patients with nodal
      metastases had normal pre-operative PSA levels, as did 54% of patients with
      tumour Gleason scores < or = 5. It was concluded that the need for pelvic lymph
      node dissection in patients with low grade tumours is questionable because of the
      low prevalence of lymph node metastases, and that the pre-operative biopsy can
      identify those patients who are at low risk for lymph node metastases.

PMID- 7505193
TI  - Positive margins after radical prostatectomy: correlation with local recurrence
      and distant progression.
AB  - The impact of positive and negative surgical margins of resection on the interval
      to and incidence of progression was analysed in 172 patients after radical
      retropubic prostatectomy combined with lymphadenectomy; 56 had positive margins.
      Lateral and apical positive margins were evaluated separately. The status of
      surgical margins was correlated with other prognostic factors, such as the T
      category, the presence or absence of seminal vesicle invasion and the G category.
      This analysis showed that positive and negative margins significantly influenced
      time to progression independently of the other prognostic factors. Positive
      margins at the apex contrary to lateral margins did not significantly influence
      time to progression. This may be due to the definition of the status of apical
      margins used in this analysis. A total of 108 patients underwent a nerve-sparing
      radical prostatectomy, which did not lead to a higher incidence of positive
      margins than the standard procedure. Prostate specific antigen accurately
      predicted tumour recurrence after radical prostatectomy. A rise of > or = 1.0
      ng/ml preceded other evidence of recurrence by a mean of 11 months.

PMID- 7505194
TI  - Tamoxifen and breast cancer--from palliation to prevention.
AB  - Tamoxifen, a synthetic antiestrogen, has been used in the treatment of all stages
      of breast cancer. The National Surgical Adjuvant Breast and Bowel Project (NSABP)
      is now in the process of evaluating the role of tamoxifen in the prevention of
      breast cancer (NSABP P-1 trial). Beneficial effects of tamoxifen in reducing
      coronary artery disease and preventing bone fractures in postmenopausal women
      will also be examined. Adjuvant therapy trials conducted during the 1980s
      provided extensive data on the biologic and possibly toxic effects of tamoxifen.
      These trials laid the groundwork to support the benefits and risks of the present
      preventional trial. The NSABP P-1 trial population of 16,000 participants will
      consist of women > or = 60 years of age and women 35-39 years old who are at
      increased risk for developing breast cancer. Nursing will play an important role
      in educating the public and counseling possible trial participants. Nurses
      monitoring the progress of this trial may witness the use of tamoxifen therapy
      come full cycle--from a palliative agent used in advanced breast cancer to a
      therapeutic agent that prevents the development of breast cancer.

PMID- 7505196
TI  - Ongoing activity of RNA polymerase II confers preferential repair of nitrogen
      mustard-induced N-alkylpurines in the hamster dihydrofolate reductase gene.
AB  - Recently, it has been demonstrated that nitrogen mustard-induced N-alkylpurines
      are excised rapidly from actively transcribing genes, while they persist longer
      in noncoding regions and in the genome overall. It was suggested that
      transcriptional activity is implicated as a regulatory element in the efficient
      removal of lesions. By treating cells or not with the transcription inhibitor
      alpha-amanitin, we have explored whether ongoing activity of RNA polymerase II
      was coordinately related to proficient repair of nitrogen mustard-induced
      alkylation products in the actively transcribed dihydrofolate reductase gene in
      the Chinese hamster ovary B11 cells. Nuclear run-off transcription analysis
      verified that alpha-amanitin completely and selectively inhibited transcription
      by RNA polymerase II. At the drug exposure examined, nitrogen mustard induced DNA
      damage capable of a complete transcription termination in the RNA polymerase II
      transcribed dihydrofolate reductase gene and reduced 28S rDNA transcription by a
      factor of 7.9. The transcription activity did partially recover following
      reincubation in drug-free medium; this recovery was about 34 and 76% of ribosomal
      28S gene transcripts and dihydrofolate reductase gene transcripts, respectively,
      after 6 h of repair incubation. alpha-Amanitin significantly inhibited the
      removal of nitrogen mustard-induced N-alkylpurines in the 5'-half of the
      essential, constitutively active dihydrofolate reductase gene, while no effect of
      alpha-amanitin was observed on the lesion removal from a noncoding region 3'
      flanking to the gene and from the genome overall. In the actively transcribed
      gene region, about 77% of N-alkylpurines were removed 21 h following drug
      exposure of cells not treated with alpha-amanitin and about 47% in 21 h in alpha
      amanitin treated cells. The global semiconservative replication seemed unaffected
      by the alpha-amanitin treatment. From these results we suggest that gene-specific
      repair of nitrogen mustard-induced N-alkylpurines is dependent on ongoing
      activity of the transcribing RNA polymerase II. The findings are discussed in
      terms of the current ideas about the mechanism of preferential DNA repair.

PMID- 7505197
TI  - Generation of cytotoxic T-lymphocytes to a self-peptide/class I complex: a model
      for peptide-mediated tumor rejection.
AB  - Cytotoxic T-lymphocytes (CTL) typically recognize foreign peptides bound to class
      I products of the major histocompatibility complex. A function of CTL is to
      identify and eliminate tumor cells that bear inappropriately expressed
      peptide/class I complexes (i.e., mutated self-peptides or self-peptides that are
      expressed at abnormally high levels). The processes that result in tolerance to
      self-antigens can undermine the effectiveness of this system by deleting or
      inactivating T-cells that might potentially be reactive with tumor-associated
      antigens. To up-regulate the response to tumor antigens it will be useful to
      develop methods whereby CTL responses to specific self-peptides can be elicited
      without damage to normal tissue. In this report a CTL response was generated in
      BALB/c mice against the ubiquitous self-peptide p2Ca (LSPFPFDL), which binds to
      Ld and is derived from the mitochondrial enzyme alpha-ketoglutarate
      dehydrogenase. CTL derived in vitro recognize specifically the p2Ca/Ld complex
      and use V beta 8 regions predominantly. The cultured cells lysed target cells
      with lower levels of p2Ca than the levels used for induction. This result
      suggests that it may be possible to use peptides at high concentrations to elicit
      CTL react with endogenous levels of a peptide/class I complex. The in vivo
      potential of the response was demonstrated by the observation that BALB/c mice,
      coinjected with a syngeneic BALB/c myeloma and exogenous p2Ca, are able to reject
      the tumor. The p2Ca/Ld system may thus provide a model for evaluating the
      parameters for effective immunotherapy with tumor-associated peptides.

PMID- 7505195
TI  - Existent T-cell and antibody immunity to HER-2/neu protein in patients with
      breast cancer.
AB  - The HER-2/neu protooncogene is amplified and overexpressed in 20-40% of invasive
      breast cancers. HER-2/neu protein overexpression is associated with aggressive
      disease and is an independent predictor of poor prognosis in several subsets of
      patients. The protein may also be related to cancer formation, with
      overexpression being detectable in 50-60% of ductal carcinomas in situ. It has
      been suggested that it might be possible to develop specific T-cell therapy
      directed against proteins involved in malignant transformation. One question is
      whether normal proteins that are overexpressed are appropriate targets for
      therapeutic immune attack. This report demonstrates that some patients with HER
      2/neu-positive breast cancers have both existent CD4+ helper/inducer T-cell
      immunity and antibody-mediated immunity to HER-2/neu protein. Initial studies
      performed on 20 premenopausal breast cancer patients identified antibodies to HER
      2/neu in 11 individuals. Similar antibody responses have been found in some
      normal individuals. The patient with the greatest antibody response was studied
      in detail. In addition to a humoral immune response this patient had evidence of
      a significant proliferative T-cell response to the HER-2/neu protein and
      peptides. Similar T-cell responses have been detected in additional patients. It
      has been assumed that patients would be immunologically tolerant to HER-2/neu as
      a self-protein and that immunity might be difficult to generate. If immunity
      could be generated, the result might be destructive autoimmunity. The current
      data support the notion that HER-2/neu-specific immunity might be used in therapy
      without destroying normal tissue but also raises questions as to the role of
      existent immunity in immune surveillance and cancer progression.

PMID- 7505198
TI  - Comparison of two antibody-based methods for elimination of breast cancer cells
      from human bone marrow.
AB  - Three monoclonal antibodies reactive with antigens abundantly expressed on human
      carcinoma cells were used to develop and compare the efficacy of immunotoxins
      (ITs) and immunobeads for purging breast cancer cells from bone marrow. ITs
      constructed as conjugates of the monoclonal antibodies and Pseudomonas exotoxin A
      showed high specific cytotoxicity against three breast cancer cell lines,
      inhibiting protein synthesis by 50% at concentrations of 4 x 10(-13) M to 1 x 10(
      10) M. Tested in a reproducible clonogenic assay, two of the ITs used at a
      concentration of 0.1 microgram/ml killed > 5 log units of MCF7 cells, the maximal
      sensitivity for assessing cytotoxic effects, and 1.5 log of T-47D tumor cells. At
      1 microgram/ml, each of the three ITs eliminated > 5 log of both cell lines. The
      immunobead procedure removed 2.0-4.1 log of tumor cells with one purging cycle
      and up to 6.0 log with two cycles. The mixture of the three ITs or immunobeads
      was not clearly superior in efficacy, compared to the use of individual
      molecules, probably reflecting an overlap in expression of the respective
      antigens in these cell lines. For both methods, the purging efficacy was not
      reduced when the tumor cells were admixed with normal bone marrow cells at a
      ratio of 1:10. The survival of colony-forming units, granulocyte/macrophage, was
      49-86% with the immunobeads and 44-75% even at high concentrations (up to 2.5
      micrograms/ml x 3) of the ITs. The results indicate that each of the two
      immunological methods can be safely used for effective elimination of tumor cells
      from the graft of breast cancer patients undergoing autologous bone marrow
      transplantation.

PMID- 7505200
TI  - U.S.-Japan Cooperative Cancer Research Program: seminar on nitric oxide synthase
      and carcinogenesis.

PMID- 7505199
TI  - Complementary DNA cloning and characterization of truncated form of c-kit in
      human colon carcinoma cells.
AB  - We have obtained a novel c-kit complementary DNA (cDNA) from a colon carcinoma
      cell line, Colo201, and characterized its structure. The size of the transcript
      in Colo201 was approximately 3.5 kilobases and it hybridized to the c-kit cDNA
      fragments encompassing the kinase domain, but not to the cDNA fragments encoding
      extracellular and transmembrane domains. The predicted protein encoded by those
      cDNAs was composed of 257 amino acids containing the NH2-terminal 25 unique amino
      acids in frame by the COOH terminal of the KIT protein. Of interest, these 25
      amino acids were encoded by intron 15 of the c-kit gene. The aberrant mRNA was
      also detected in another colon carcinoma cell line, BM314. The translation of
      this message in Colo201 was confirmed by flow cytometry and immunoblot analysis.
      This is the first report describing the aberrant transcript of c-kit in human
      tumor cells, and it is suggested that truncated form of c-kit might play a role
      in the onset and development of human colon carcinoma.

PMID- 7505201
TI  - MCF-10A cells infected with the int-2 oncogene induce angiogenesis in the chick
      chorioallantoic membrane and in the rat mesentery.
AB  - A growing body of evidence demonstrates the relevant role of the int-2 (FGF-3)
      oncogene in human carcinomas. To investigate its angiogenic activity, the human
      epithelial mammary cell line MCF-10A was infected with a retroviral expression
      vector carrying the int-2 oncogene. Infected cells were entrapped in an alginate
      pellet and placed on the chorioallantoic membrane of chick embryos. After 7 days,
      a dense capillary network was found to grow toward the pellet, whereas parental
      cells did not show any angiogenic activity. Conditioned medium from int-2
      infected cells was injected i.p. twice daily into rats over a period of 10 days.
      The mesentery of treated rats showed numerous small blood vessels originating
      from larger vascular arcades and growing through the stromal layer of the
      mesentery. In control experiments, neither medium for cell culture nor
      conditioned medium from parental cells was found to induce angiogenesis. In
      conclusion, the stimulation of blood vessel growth by int-2-infected cells
      suggests that the production of the int-2 protein is associated with the
      acquisition of the angiogenic phenotype.

PMID- 7505202
TI  - The Mauriceville plasmid reverse transcriptase can initiate cDNA synthesis de
      novo and may be related to reverse transcriptase and DNA polymerase progenitor.
AB  - We show that the reverse transcriptase (RT) encoded by the Mauriceville
      mitochondrial plasmid of Neurospora closely resembles viral RNA-dependent RNA
      polymerases in initiating cDNA synthesis opposite the penultimate C residue of a
      3' tRNA-like structure and has the unprecedented ability for a DNA polymerase to
      initiate DNA synthesis at a specific site in a natural template without a primer.
      The Mauriceville plasmid enzyme can also use DNA or RNA primers in a manner
      suggesting how a primitive RT could have evolved from an RNA-dependent RNA
      polymerase into retroviral and other types of RTs. The characteristics of the
      Mauriceville plasmid RT suggest that it may be related to the progenitor of
      present-day RTs and DNA polymerases.

PMID- 7505203
TI  - Tumor suppression by RNA from the 3' untranslated region of alpha-tropomyosin.
AB  - NMU2, a nondifferentiating mutant myogenic cell line, gives rise to
      rhabdomyosarcomas in mice. We show that constitutive expression of RNA from 0.2
      kb of the alpha-tropomyosin (Tm) 3' untranslated region (UTR), but not control
      3'UTRs, suppresses anchorage-independent growth and tumor formation by NMU2
      cells. When beta-galactosidase (beta-gal)-labeled cells were implanted into
      muscles of adult mouse hindlimbs, Tm 3'UTR expression suppressed the
      proliferation, invasion, and destruction of muscle tissues characteristic of
      NMU2. In the rare tumors that developed from Tm 3'UTR transfectants, RNA
      expression was extinguished. These results suggest that suppression of
      tumorigenicity is dependent on the continued expression of Tm transcripts lacking
      a coding region. We conclude that untranslated RNAs can function as regulators
      (riboregulators) that suppress tumor formation.

PMID- 7505204
TI  - Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a
      proliferative factor for primitive hematopoietic cells.
AB  - Cloning of a ligand for the murine flt3/flk-2 tyrosine kinase receptor was
      undertaken using a soluble form of the receptor to identify a source of ligand. A
      murine T cell line, P7B-0.3A4, was identified that appeared to express a cell
      surface ligand for this receptor. A cDNA clone was isolated from an expression
      library prepared from these cells that was capable, when transfected into cells,
      of conferring binding to a soluble form of the flt3/flk-2 receptor. The cDNA for
      this ligand encodes a type I transmembrane protein that stimulates the
      proliferation of cells transfected with the flt3/flk-2 receptor. A soluble form
      of the ligand stimulates the proliferation of defined subpopulations of murine
      bone marrow and fetal liver cells as well as human bone marrow cells that are
      highly enriched for hematopoietic stem cells and primitive uncommitted progenitor
      cells.

PMID- 7505205
TI  - Molecular cloning and expression of the Fas ligand, a novel member of the tumor
      necrosis factor family.
AB  - The Fas antigen (Fas) belongs to the tumor necrosis factor (TNF)/nerve growth
      factor receptor family, and it mediates apoptosis. Using a soluble form of mouse
      Fas, prepared by fusion with human immunoglobulin Fc, Fas ligand was detected on
      the cell surface of a cytotoxic T cell hybridoma, PC60-d10S. A cell population
      that highly expresses Fas ligand was sorted using a fluorescence-activated cell
      sorter, and its cDNA was isolated from the sorted cells by expression cloning.
      The amino acid sequence indicated that Fas ligand is a type II transmembrane
      protein that belongs to the TNF family. The recombinant Fas ligand expressed in
      COS cells induced apoptosis in Fas-expressing target cells. Northern
      hybridization revealed that Fas ligand is expressed in activated splenocytes and
      thymocytes, consistent with its involvement in T cell-mediated cytotoxicity and
      in several nonlymphoid tissues, such as testis.

PMID- 7505206
TI  - Expression cloning of a functional glycoprotein ligand for P-selectin.
AB  - The initial adhesive interactions between circulating leukocytes and endothelia
      are mediated, in part, by P-selectin. We now report the expression cloning of a
      functional ligand for P-selectin from an HL-60 cDNA library. The predicted amino
      acid sequence reveals a novel mucin-like transmembrane protein. Significant
      binding of transfected COS cells to P-selectin requires coexpression of both the
      protein ligand and a fucosyltransferase. This binding is calcium dependent and
      can be inhibited by a neutralizing monoclonal antibody to P-selectin.
      Cotransfected COS cells express the ligand as a homodimer of 220 kd. A soluble
      ligand construct, when coexpressed with fucosyltransferase in COS cells, also
      mediates P-selectin binding and is immunocrossreactive with the major HL-60
      glycoprotein that specifically binds P-selectin.

PMID- 7505208
TI  - Immunohistochemical distribution of amyloid precursor protein during normal rat
      development.
AB  - This study focused on the immunohistochemical identification of the beta/A4
      amyloid precursor protein (APP) in various developmental stages of both the rat
      central nervous system (CNS) and the peripheral nervous system (PNS). A
      comparative study with myelin basic protein (MBP) and synaptophysin (SYP)
      facilitated the understanding of neuronal maturation and synaptogenesis on both
      prenatal and postnatal development. Our immunohistochemical study revealed APP to
      be widely distributed through the nervous system while existing mainly in the
      cytoplasm, dendrites and axons of the neurons. However, immunoreactivity was also
      observed in either the ependymal cells or the choroid plexus epithelial cells.
      Our immunostaining was carried out by the hydrated autoclaving method and
      revealed the expression of APP at embryonic day 15 in the neuron of the
      mesencephalic nucleus of the trigeminal nerve and the anterior horn of the spinal
      cord, trigeminal and spinal ganglion, ependymal cells and the choroid plexus. We
      thus observed dramatic changes of APP expression in the cerebellum from the
      embryonic stage. The maturation of synaptogenesis in the cerebellar molecular
      layer was parallel to the extension of the dendrites of Purkinje cells, which
      revealed immunoreactivity for APP. These findings suggested that APP played an
      important role in neuronal maturation and synaptogenesis. Thus, APP is considered
      to be a useful marker for neuronal development.

PMID- 7505207
TI  - Insulin-like growth factor I inhibits induction of nitric oxide synthase in
      vascular smooth muscle cells.
AB  - Experiments were designed to examine whether or not insulin-like growth factor I
      (IGF-I), which is produced by vascular cells in response to injury, affects the
      production of nitric oxide evoked by the inducible nitric oxide synthase in
      cultures of smooth muscle cells from the rat aorta. Nitric oxide production was
      assessed indirectly by the measurement of nitrite accumulation and nitric oxide
      synthase activity by determining the formation of L-citrulline from L-arginine.
      Nitric oxide synthase was induced in vascular smooth muscle cells that had been
      exposed to interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF
      alpha). IGF-I inhibited, in a concentration-dependent manner, the production of
      nitrite and L-citrulline evoked by IL-1 beta or TNF-alpha. The inhibition caused
      by IGF-I required the presence of the growth factor during the induction of
      nitric oxide synthase. Two IGF-I-related proteins, IGF-II and insulin, also
      inhibited, but to a smaller extent, the release of nitrite and the formation of L
      citrulline stimulated by IL-1 beta. Under bioassay conditions, the perfusates
      from columns containing IL-1 beta-treated smooth muscle cells relaxed rings of
      rat aorta without endothelium that had been contracted with phenylephrine; these
      relaxations were reversed by nitro-L-arginine. Addition of IL-1 beta-treated
      vascular smooth muscle cells to indomethacin-treated platelets inhibited their
      aggregation to thrombin; methylene blue prevented this inhibition. Control smooth
      muscle cells or cells exposed to IGF-I alone did not have such effects.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7505209
TI  - Satellite oligodendrocytes and myelin are displaced in the cortex of the reeler
      mouse.
AB  - The spatial distribution of satellite (perineuronal) oligodendrocytes and myelin
      was studied in the cortices of normal and reeler mice. In normal mice, satellite
      oligodendrocytes were concentrated in the inner third of the cortex. In reeler
      mice, satellite oligodendrocytes were present beneath the pial surface and
      distributed throughout the width of the cortex. In reeler mice, but not normal
      mice, myelin was present in patches beneath the pia and distributed throughout
      the width of the cortex. The abnormal position of satellite oligodendrocytes and
      myelin coincides with the displacement of neurons and axons in the cortex of
      reeler mice. These studies indicate that the distribution of cortical
      oligodendrocytes is influenced by neuronal/axonal position.

PMID- 7505210
TI  - Studies on zinc and angiotensin-converting enzyme.

PMID- 7505211
TI  - Phenotypic analysis and characterization of CD34+ cells from normal human bone
      marrow, cord blood, peripheral blood, and mobilized peripheral blood from
      patients undergoing autologous stem cell transplantation.
AB  - Single- and multicolor flow cytometry were used to define progenitor subsets in
      normal human bone marrow and peripheral blood, cord blood, and blood following
      mobilization of CD34+ progenitor cells by cyclophosphamide or
      cyclophosphamide/etoposide/G-CSF treatment. CD34 cells were quantitated and
      subsets of CD34+ cells were defined by coexpression of CD33, CD13, CD10, CD19,
      CD45RA, and CD71. Myeloid and erythroid progenitors were quantitated by sorting
      single CD34+ cells into individual wells of 96-well plates containing
      methylcellulose, IL-3, GM-CSF, G-CSF, IL-6, and erythropoietin. Comparative
      studies of CD34 cells showed that the percentage of CD34+ mononuclear cells was
      greatest in blood samples from patients following mobilization treatment with
      cyclophosphamide/etoposide/G-CSF averaging 2%. By comparison, the remaining
      sample groups ranged from 1.68 to 0.15% CD34 cells in this order, bone marrow >
      cord blood > cyclophosphamide mobilized blood > peripheral blood. Comparison of
      CD34 cells per milliliter of bone marrow or blood showed a range of 22.4 x 10(4)
      to 0.65 x 10(4)/ml in the following order, bone marrow > chemotherapy/etoposide/G
      CSF > cord blood > cyclophosphamide-mobilized blood. Comparative analysis of CD34
      subsets from different sources showed significant differences, particularly bone
      marrow and blood samples. A distinct population of CD34+ CD19+ (Leu 12) CD10+
      (CALLA) pre-B lymphocyte cells was defined in bone marrow with lower side and
      forward light scatter characteristics and was variable between donors (29.8 +/-
      16.9%, mean +/- 1 SD; range, 3-54%; n = 8). This population was not found to a
      significant degree in blood and also expressed CD45RA (Leu 18). Coexpression
      studies of CD45RA and CD71 (transferrin receptor) expression on CD34+ cells
      defined a CD45RA- CD71+ population containing 89 +/- 6.3% (n = 4) BFU-E and a
      CD45RA+ CD71+ population that contained all CFU-GM (n = 4). LeuM7 (CD13) stained
      a larger percentage to a greater intensity than MY7 (CD13). Coexpression of
      CD45RA (Leu 18) and CD13 (LeuM7) defined a subset of CD13+ CD45RA+ cells enriched
      for CFU-GM and CFU-M with a cloning efficiency of 31%. Coexpression of CD33 (MY9)
      and CD13 (MY7) defined a population that was predominantly CFU-GM with a cloning
      efficiency of 38%. These studies define CD34+ phenotypes containing pure
      populations of B lymphocyte, granulocyte-macrophage, or erythroid progenitors and
      demonstrate the utility of multiparameter flow cytometry to define lineage
      committed CD34+ cells.

PMID- 7505212
TI  - Interleukin-1 and B7/CD28 interaction regulate interleukin-6 production by human
      T cells.
AB  - Production of interleukin-6 (IL-6) by the Th2 subset of murine T cells supposedly
      contributes to regulation of humoral immunity. Little information exists on IL-6
      production by human T cells. We examined the requirements for IL-6 production by
      purified human blood T cells, completely depleted of IL-6-producing monocyte
      accessory cells. Immobilized anti-CD3 mAb alone (coated on the culture wells) was
      unable to induce IL-6 production, although it could induce production of IL-2 and
      TNF-alpha. Addition of rIL-1 beta as an accessory signal to anti-CD3-stimulated
      human T cells induced IL-6 mRNA expression and protein secretion, while IL-2, IL
      4, GM-CSF, IFN-gamma, or TNF-alpha did not have any effect. In the presence of IL
      1 beta, both CD4+ and CD8+ T cells were able to produce IL-6. We also
      demonstrated that phorbol 12-myristate 13-acetate (PMA) or triggering of the CD28
      molecule is an effective helper signal for IL-6 production by anti-CD3-stimulated
      T cells. Efficient CD28 ligation was done either by anti-CD28 mAb or by binding
      to its natural ligand B7/BB1, presented on the 3T6 mouse fibroblast cell line
      coexpressing transfected human Fc gamma RII (CD32) (to immobilize anti-CD3) and
      B7/BB1. Finally, we found that combinations of IL-1 beta with anti-CD28 mAb or
      PMA with anti-CD28 mAb were highly synergistic helper signals for IL-6
      production. We conclude that IL-6 production by T cells is not induced by T cell
      receptor triggering alone, but different intracellular signaling pathways
      activated by IL-1 beta, CD28 ligation, or PMA efficiently coinduce IL-6
      production.

PMID- 7505213
TI  - Monoclonal anti-idiotype antibody to HSV-1 neutralizing monoclonal antibody:
      production and characterization.
AB  - This study is an attempt to produce and characterize murine monoclonal antibodies
      directed against the paratope of HSV-1 neutralizing monoclonal antibody.
      Monoclonal antibody 138 C5G10 which was neutralising and directed to 120 K
      antigen gB of HSV-1 was used as the idiotype. We were able to produce three Ab-2
      monoclonal antibodies as characterized using immunofluorescence, ELISA and RIA.
      The findings of the present study suggest that two antiidiotypes 3AiB3E10 and
      3AiB5D10 share the same unique fine specificity while 3AiB3C9 has a different
      specificity on 138 C5G10 paratope. The utility of such 'surrogate' antigens in
      serological assays and modulation of immune response is discussed.

PMID- 7505215
TI  - Parenterally transmitted hepatitis: viruses, vaccines, and antiviral therapy.
AB  - The introduction of safe and effective vaccines as well as the identification of
      antiviral therapy that eradicates virus in many infected patients augurs well for
      the control of HBV and, by extension, HDV infection. The key to ultimate success
      will be the universal availability of immunization. The recent elucidation of the
      hepatitis C genomic structure will eventually lead to fundamental understanding
      of the mechanisms underlying the life cycle of HCV, which appears to elude both
      natural and synthetic defensive measures. The best hope for control of this virus
      in the near future rests in careful screening of the blood supply and alteration
      of high-risk lifestyles. The next phase of antiviral and vaccine development for
      all of these agents will depend on recently acquired knowledge of virus-specific
      enzymatic processes, molecular interactions between viruses and host cells, and
      our ability to interfere selectively with these processes.

PMID- 7505214
TI  - The effect of intensive insulin therapy on the insulin-regulatable glucose
      transporter (GLUT4) expression in skeletal muscle in type 1 diabetes.
AB  - Studies in normal man and rodents have demonstrated that the expression of the
      dominant glucose transporter in skeletal muscle, GLUT4, is regulated by insulin
      at supraphysiological circulating levels. The present study was designed to
      determine whether intensified insulin replacement therapy for 24 h given to
      patients with Type 1 diabetes in poor metabolic control was associated with an
      adaptive regulation of GLUT4 mRNA and protein levels in vastus lateralis muscle.
      Nine Type 1 diabetic patients with a mean HbA1c of 10.3% were included in the
      protocol. After intensified treatment with soluble insulin for 24 h the fasting
      plasma glucose concentration decreased from 20.8 +/- 2.3 (SD) to 8.7 +/- 2.3 mmol
      1-1, whereas the fasting serum insulin level increased from 0.06 +/- 0.02 to 0.17
      +/- 0.09 nmol 1-1. However, despite a 2.8-fold increase in serum insulin levels
      and more than a halving of the plasma glucose concentration for at least 15 h no
      significant alterations occurred in the amount of GLUT4 protein (0.138 +/- 0.056,
      poor control vs 0.113 +/- 0.026 arb. units, improved control, p = 0.16) or GLUT4
      mRNA (96432 +/- 44985, poor control vs 81395 +/- 25461 arb. units, improved
      control, p = 0.54). These results suggest, that in spite of evidence that high
      insulin levels affect GLUT4 expression in muscle, changes in serum insulin within
      the physiological range do not play a major role in the short-term regulation of
      GLUT4 expression in Type 1 diabetic patients.

PMID- 7505216
TI  - Expression of cell adhesion molecules in corneal graft failure.
AB  - Corneal graft failure is frequently mediated by uncontrolled inflammatory
      disease. We studied the expression of cell adhesion molecules in seven
      penetrating keratoplasty specimens with graft failure and in a normal eye bank
      cornea using immunohistochemical staining and monoclonal antibodies against
      intercellular adhesion molecule-1 (ICAM-1, CD54), lymphocyte function-associated
      antigen-1 (LFA-1, CD11a/CD18), vascular cell adhesion molecule-1 (VCAM-1), E
      selectin, and major histocompatibility complex (MHC) class II antigen (HLA-DR).
      ICAM-1 and HLA-DR were expressed on keratocytes and the corneal endothelium in
      six of the seven specimens. ICAM-1 expression was strongest in the corneas with
      the most severe inflammation (corneal allograft rejection and severe intraocular
      inflammation). LFA-1 is a counter-receptor for ICAM-1, and infiltration with
      leukocytes expressing either the alpha or beta chain of LFA-1 was found in areas
      of ICAM-1 expression in four of the seven corneas. In contrast, E-selectin was
      expressed in the stroma in only two specimens, and VCAM-1 in one specimen.
      Expression of cell adhesion molecules or MHC class II antigen were not detected
      in the normal eye bank cornea. These data suggest that ICAM-1 expression may play
      an important role in the development of corneal graft failure. Furthermore,
      monoclonal antibodies to block ICAM-1 or its ligands may inhibit the development
      of corneal inflammation.

PMID- 7505217
TI  - Clinical evaluation of plasma des-gamma-carboxy prothrombin as a marker protein
      of hepatocellular carcinoma in patients with tumors of various sizes.
AB  - We measured des-gamma-carboxyprothrombin (DCP) (prothrombin induced by vitamin K
      absence or antagonist-II, abbreviated as PIVKA-II) by a newly developed enzyme
      immunoassay using an anti-DCP monoclonal antibody in 665 human subjects, of which
      112 were patients with hepatocellular carcinoma (HCC). PIVKA-II was elevated to
      more than 0.1 AU/ml in 54 of the 112 patients (48.2%) with HCC, while it was
      positive only in 7.1% of those with liver cirrhosis and 3.1% of those with
      chronic hepatitis. Three patients with elevated PIVKA-II greater than 0.1 AU/ml
      who had been diagnosed as having liver cirrhosis by ultrasonography and computed
      tomography at the start of this study developed a diffuse type of HCC three or
      six months later, which was detected by angiography. No obvious correlation was
      observed between plasma PIVKA-II concentration and serum alpha-fetoprotein (AFP)
      level in HCC patients. Of the 112 HCC patients, 40.2% showed an increase in AFP
      to above 200 ng/ml. In the remaining patients, 32.8% had a PIVKA-II concentration
      greater than 0.1 AU/ml. In these patients with a negative or low serum AFP
      concentration, PIVKA-II proved to be a valuable tumor marker for laboratory
      diagnosis of HCC. Among them, 59.8% tested positive for PIVKA-II and/or AFP.
      Thus, combination assay with PIVKA-II and AFP seems useful for increasing the
      accuracy of laboratory diagnosis of HCC. None of patients with a solitary tumor
      smaller than 2 cm had elevated PIVKA-II. In patients with larger-sized and
      multiple HCC, positive results of elevated PIVKA-II were more frequent than those
      of increased AFP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505218
TI  - [Liver damage in lymphoma and its clinical significance].
AB  - The incidence of liver damage was evaluated in 125 patients with lymphoma. The
      result showed that liver dysfunction was seen in 44 cases and liver involvement
      in 30 cases. The liver damage due to the drug toxicity was not observed. HBV
      could cause severe clinical sequelae after chemotherapy in the lymphoma. Patients
      with liver damage had worse prognosis.

PMID- 7505219
TI  - Pancreatitis in a patient with AIDS.

PMID- 7505220
TI  - An antibody that binds the immunoglobulin CDR3-like region of the CD4 molecule
      inhibits provirus transcription in HIV-infected T cells.
AB  - We used the polymerase chain reaction (PCR) to study which step(s) of the human
      immunodeficiency virus type 1 (HIV-1) life cycle may be blocked following
      treatment of HIV-exposed CEM cells with 13B8-2, a monoclonal antibody (mAb)
      specific for the immunoglobulin (Ig) CDR3-like region of the CD4 molecule and
      able to inhibit the productive infection of CEM cells by HIV-1. The presence of
      viral RNA was investigated and found in 13B8-2 mAb-treated CEM cells 30 min after
      viral exposure; the full-length viral DNA was found at 24 h post-infection. We
      also found integrated forms of viral DNA at 24 h post-infection. However, the
      integrated provirus was transcriptionally inactive in 13B8-2 mAb-treated cells,
      as demonstrated by the absence of spliced HIV-1 mRNA. The lack of HIV
      transcription under 13B8-2 mAb treatment was confirmed by chloramphenicol
      acetyltransferase (CAT) assay. We conclude that the inhibition of viral gene
      transcription accounts for the lack of progeny virions in culture supernatants of
      cells treated with this anti-CD4 mAb. We also demonstrate that 13B8-2 blocks
      viral production from chronically infected cells and restores CD4 cell-surface
      expression on CEM cells containing an integrated provirus(es). We found this
      effect to be reversible. Moreover, we demonstrate that 13B8-2 mAb treatment is
      efficient on different HIV-1 and HIV-2 virus isolates. These results may have
      major implications for the treatment of AIDS.

PMID- 7505221
TI  - The tyrosine phosphorylation site of the acetylcholine receptor beta subunit is
      located in a highly immunogenic epitope implicated in channel function: antibody
      probes for beta subunit phosphorylation and function.
AB  - Tyrosine phosphorylation of the nicotinic acetylcholine receptor (AChR) seems to
      be involved in AChR desensitization and localization on the postsynaptic
      membrane. This study reveals a probable function of the single known beta subunit
      phosphorylation site (beta Tyr355) and provides suitable tools for its study. The
      epitopes for 15 monoclonal antibodies (mAbs) against the cytoplasmic side of the
      AChR beta subunit were precisely mapped using > 100 synthetic peptides attached
      on polyethylene rods. Eleven mAbs bound to a very immunogenic cytoplasmic epitope
      (VICE-beta) on Torpedo beta 352-359, which contains the beta Tyr355, and to the
      corresponding sequence of human AChR. The contribution of each VICE-beta residue
      to mAb binding was then studied by peptide analogues having single residue
      substitutions. Overall, each of the residues beta 354-359, including beta Tyr355,
      proved critical for mAb binding. Two of our four mAbs known to block the ion
      channel were found to bind at (mAb148) or close (mAb10) to VICE-beta. Tyrosine
      phosphorylation of Torpedo AChR by endogenous kinase(s) selectively reduced
      binding of some VICE-beta mAbs, including the channel blocking mAb148. We
      conclude that VICE-beta probably plays a key role in AChR function. Elucidation
      of this role should be facilitated by the identified mAb tools.

PMID- 7505223
TI  - Follow-up of a cohort of men with untreated benign prostatic hyperplasia.
AB  - A cohort of 266 men with untreated benign prostatic hyperplasia (BPH) identified
      in a community-based survey were followed for a period of 1 year. Although the
      overall prevalence of urinary symptoms increased during the year, substantial
      within-subject variation in urinary symptomatology occurred, with up to a quarter
      of men reporting urgency and dribbling to have improved whilst one third of men
      reported other urinary symptoms to have deteriorated. Levels of bothersomeness
      caused by urinary symptoms did not show much change during the period of follow
      up. An overall increase of 19% in urinary peak flow which was also consistent
      across all age groups was present at 1 year compared with baseline, even after
      adjusting for increased urinary void volume. A slow progression in the extent to
      which interference with selected activities of daily living by urinary
      dysfunction occurred. This was greater in men of working age (40-64 years),
      compared with men of retirement age (65-79 years). A longer period of observation
      is required in order to determine the extent to which a consistent pattern of
      urinary symptomatology exists in untreated BPH, as well as whether interference
      with daily living activities continues to progress over time.

PMID- 7505224
TI  - Efficacy and safety of the alpha-1 blocker doxazosin in the treatment of benign
      prostatic hyperplasia. Analysis of 5 studies. Doxazosin Study Groups.
AB  - Controlled clinical studies have demonstrated that blockade of alpha 1-adrenergic
      receptors relaxes prostatic muscle tone and decreases the symptoms of benign
      prostatic hyperplasia (BPH). Doxazosin, a once-daily quinazoline derivative and
      postsynaptic alpha 1-adrenoceptor antagonist, proven as treatment for
      hypertension, was evaluated in the treatment of BPH in dosages of 1-16 mg. 456
      BPH patients (287 doxazosin-treated and 169 placebo-treated) were evaluated for
      efficacy and safety in five double-blind, placebo-controlled clinical studies.
      Doxazosin treatment resulted in improvements in both urodynamic and symptomatic
      parameters associated with BPH. Efficacy was only assessed in 1, 2 and 4 mg.
      Adverse experiences were reported in 127 (44.3%) of the patients treated with
      doxazosin and in 49 (29%) of the patients treated with placebo. Fifteen (5.2%)
      doxazosin patients and 4 (2.4%) placebo patients withdrew from the studies due to
      adverse effects. Results from these five clinical trials demonstrate doxazosin is
      effective and safe and well tolerated in both normotensive and hypertensive
      patients with BPH.

PMID- 7505222
TI  - Selection of a 'minimal' glutaminyl-tRNA synthetase and the evolution of class I
      synthetases.
AB  - The evolution of the aminoacyl-tRNA synthetases is intriguing in light of their
      elaborate relationship with tRNAs and their significance in the decoding process.
      Based on sequence motifs and structure determination, these enzymes have been
      assigned to two classes. The crystal structure of Escherichia coli glutaminyl
      tRNA synthetase (GlnRS), a class I enzyme, complexed to tRNA(Gln) and ATP has
      been described. It is shown here that a 'minimal' GlnRS, i.e. a GlnRS from which
      domains interacting with the acceptor-end and the anticodon of the tRNA have been
      deleted, has enzymatic activity and can charge a tRNA(Tyr)-derived amber
      suppressor (supF) with glutamine. The catalytic core of GlnRS, which is
      structurally conserved in other class I synthetases, is therefore sufficient for
      the aminoacylation of tRNA substrates. Some of these truncated enzymes have lost
      their ability to discriminate against non-cognate tRNAs, implying a more specific
      role of the acceptor-end-binding domain in the recognition of tRNAs. Our results
      indicate that the catalytic and substrate recognition properties are carried by
      distinct domains of GlnRS, and support the notion that class I aminoacyl-tRNA
      synthetases evolved from a common ancestor, jointly with tRNAs and the genetic
      code, by the addition of non-catalytic domains conferring new recognition
      specificities.

PMID- 7505225
TI  - Prostatic spiral versus prostatic urolume wallstent for urinary retention due to
      benign prostatic hyperplasia. A long-term comparative study.
AB  - Thirty-eight high-risk surgical patients with urinary retention due to benign
      prostatic hyperplasia (BPH) were treated by placement of a prostatic spiral under
      local anesthesia (group 1: 20 patients) or a prostatic stent under intravenous
      sedation (group 2: 18 patients). At the 1-year follow-up, mean peak flow rate,
      residual urine volume and subjective symptoms scale were significantly better in
      the stent group (p < 0.01). The rate of postoperative urinary incontinence and
      dislocation of the device was greater in the spiral group. Cystoscopic
      manipulation and removal of the device were definitely easier with the spiral.
      Both the prostatic spiral and stent have specific roles in the treatment of
      urinary retention in the unfit BPH patient. The selection of the most suitable
      device depends on accurate patient assessment.

PMID- 7505226
TI  - Needle ablation using radio frequency current as a treatment for benign prostatic
      hyperplasia: experimental results in ex vivo human prostate.
AB  - Transurethral needle ablation of the prostate using low level radiofrequency (RF)
      energy was investigated in a human ex vivo model. RF power applications at a
      variety of power levels for various treatment times elicited marked thermal
      lesions of consistent sizes in prostatic adenomas. Tissue temperature was found
      to be the fundamental lesioning parameter. Lesions were created whenever tissue
      temperature exceeded 45 degrees C. Lesion size correlated with RF power delivery
      and electrode length. Monitoring of the tissue impedance assisted in controlling
      efficacious lesioning. RF power applications of 5-7.5 W for 3 min are suggested
      as the 'ideal' setting to treat human prostatic adenomas, taking into
      consideration the lesion size and time to achieve ablative temperatures.

PMID- 7505227
TI  - Transurethral needle ablation (TUNA): thermal gradient mapping and comparison of
      lesion size in a tissue model and in patients with benign prostatic hyperplasia.
AB  - A new device has been development for treating benign prostatic hyperplasia (BPH)
      that is performed as an outpatient procedure. the device (transurethral needle
      ablation or TUNA) employs needles that deliver low-level radiofrequency (RF)
      power locally at high temperature to ablate hyperplastic prostate tissue. During
      the TUNA procedure the temperature proximal to the needle tips is measured with
      thermocouples within the needle's protective shields and urethral temperature is
      measured via a thermocouple contained within the catheter tip. Tissue impedance
      is also measured by the TUNA catheter since it is well known from other thermal
      treatment methods that thermal destruction of prostatic tissue depends upon a
      particular prostate's tissue composition and thermoregulation. Because of this
      variation in prostates, a nomogram guide for setting the TUNA device was created
      using a turkey breast tissue model. Lesion sizes created at particular settings
      in the turkey breast model were similar to those created at the same settings in
      patients with BPH. In addition, local thermal gradients within the TUNA lesions
      were visualized and mapped using an infrared thermal imaging system which
      demonstrated that central lesion temperature with the device is approximately 80
      100 degrees C.

PMID- 7505228
TI  - Transurethral needle ablation (TUNA): safety, feasibility, and tolerance of a new
      office procedure for treatment of benign prostatic hyperplasia.
AB  - Many attempts have been made to develop a method for treating benign prostatic
      hyperplasia (BPH) that is minimally invasive, efficacious, and low cost. The
      transurethral needle ablation (TUNA) device has recently been developed to treat
      BPH by selectively ablating hyperplastic prostatic tissue. A special catheter
      incorporates needles that deliver low-level radiofrequency power directly to a
      very localized area of the prostate. The needles have adjustable shields to
      protect the urethra if desired or necessary. It is positioned via transrectal
      ultrasound or direct vision. A pilot study was performed in patients to evaluate
      TUNA feasibility via histopathological measurement of thermal lesion size and
      TUNA safety by: (1) monitoring urethral and rectal temperatures; (2) assessing
      the ability to localize lesions, and (3) determining patient tolerance of the
      procedure without anesthesia. Twenty patients were treated using TUNA prior to
      scheduled retropubic prostatectomy. The surgical prostatic specimens were
      recovered from 1 day to 1 month after TUNA, were step-sectioned, and examined
      histologically. Patients were 68 years old on average with prostate weight
      varying from 14 to 88 g. The TUNA procedure averaged 27 min, 4 lesion treatments
      per prostate, and 4-15 W of power applied for 3 min. Proximal lesion temperature
      was about 40-50 degrees C with central lesion temperatures of about 80-100
      degrees C. Urethral temperature averaged 37-42 degrees C and rectal temperature
      remained unchanged. Macroscopic examination of the specimens demonstrated
      localized lesions averaging 12 x 7 mm. Microscopic examination showed larger
      lesions of extensive coagulative necrosis averaging 30 x 15 mm. Specific
      immunohistochemical staining showed destruction of all tissue
      components.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505229
TI  - Treatment of advanced prostate cancer with the combination of finasteride plus
      flutamide: early results.
AB  - In an attempt to maximize the quality of life of advanced prostate cancer
      patients on prolonged total androgen ablation and to minimize side effects, we
      have devised a strategy of 'sequential androgen blockade'. Animal studies have
      demonstrated that the combination of the 5 alpha-reductase inhibitor finasteride
      and the antiandrogen flutamide was as effective as a luteinizing hormone
      releasing hormone analog and flutamide in inhibiting the growth of the prostate.
      In a pilot trial, 10 potent patients with clinical stage C and D1 prostate cancer
      were given the combination of finasteride (5 mg b.i.d.) and flutamide (125-250 mg
      t.i.d.). Eight of ten men remained potent. At 3 months the mean prostate-specific
      antigen level of all patients was 3.8 ng/ml (34 ng/ml prior to therapy). In all
      patients serum testosterone increased and those with the highest increase
      demonstrated gynecomastia. The combination was easily tolerable and side effects
      were few. This treatment regime appears to offer the benefits of total androgen
      blockade, is less expensive and has fewer side effects. Further trials are
      warranted.

PMID- 7505230
TI  - Screening for prostate cancer.
AB  - Early-stage prostate cancer is usually asymptomatic and therefore, in the past,
      has often gone undetected, unless diagnosed by a digital rectal examination. More
      recently, new tests have been introduced, namely prostate-specific antigen and
      transrectal ultrasound, in order to improve the detection of early-stage disease.
      Considerable debate exists about the routine use of these screening tests. This
      article addresses issues such as which tests are the most predictable, the
      outcome of screening in terms of benefits (or not) to the patient and the
      advantages and disadvantages of screening itself.

PMID- 7505231
TI  - Neoadjuvant hormonal deprivation before radical prostatectomy.
AB  - Our experience with 40 patients receiving complete androgen blockade with
      luteinizing hormone-releasing hormone agonist and flutamide, prior to radical
      surgery, has shown a definitive decrease in prostate volume of 40-50%. This
      significant reduction in volume, induced by the neoadjuvant therapy, seems to
      facilitate the dissection of the prostate from closely vulnerable structures,
      with a reduction in blood loss (average 400 ml) and in time of surgery (average
      135 min). Clinical downstaging was observed in one third of the patients, but the
      final pathological staging clearly showed that it is difficult to confirm this
      issue. Downgrading was not observed, but this is difficult to assess since the
      biopsies are not representative of the entire heterogeneous tumor. Prostate
      specific antigen (PSA) dropped to undetectable levels in 59% of the patients 3
      months after hormone suppression. Among these, 80% had pT2 and only 13% had pT3
      tumors while there was 1 pT0 patient. Patients who still had a PSA of > 4 ng/ml
      after neoadjuvant therapy all had stage PT3-PT4 disease. Histological changes
      were observed in both the non-neoplastic tissue and the prostatic carcinoma, with
      effects being more marked in the latter. PSA, after 3 months of neoadjuvant
      hormone treatment, might have a useful predictive value in patient selection for
      radical surgery, since 86% of patients with undetectable PSA had tumors confined
      to the gland (pT2-B2). Large, prospective, randomized studies, comparing radical
      prostatectomy against radical prostatectomy with neoadjuvant complete androgen
      deprivation in locally advanced (T2-T3N0M0) prostatic carcinoma, are needed to
      assess the true influence of the combined approach on local control, time to
      progression and overall survival.

PMID- 7505232
TI  - Value of prostate-specific antigen as a tumor marker.
AB  - Prostate-specific antigen (PSA) is the most important tumor marker for prostate
      cancer. However, the diagnostic limits of PSA have to be taken into consideration
      because PSA is also secreted by normal prostate tissue and, with benign prostatic
      hyperplasia, false positives are possible. Although there is a direct correlation
      between the serum PSA concentration and the clinical stage of the tumor, PSA is
      not sufficiently reliable to determine the stage of the disease on an individual
      basis. Low serum PSA concentrations (less than 20 ng/ml) in patients with
      previously untreated prostate cancer seem to be predictive for a negative bone
      scan. Serum PSA values also reflect the prognosis of the patient. With respect to
      monitoring patients after definitive therapy, PSA is a very sensitive tumor
      marker. However, in a small number of patients PSA-negative tumor recurrences
      occur.

PMID- 7505233
TI  - Chemohormonal and immunohormonal approaches in advanced prostatic carcinoma.
AB  - The standard palliative treatment for patients with advanced prostate cancer has
      for the past 50 years been androgen withdrawal. However, owing to the presence of
      hormone-insensitive cell clones, the benefits of this approach have now appeared
      to reach their optimum. It is now generally believed that further major
      therapeutic advances in the treatment of prostate cancer are unlikely, unless
      consideration is given to these hormonally independent cells. Two possible
      alternative strategies which address this problem are chemohormonal and
      immunohormonal approaches, both of which are discussed in detail in this article.

PMID- 7505234
TI  - Management of relapsed prostatic carcinoma following primary treatment.
AB  - Early diagnosis and monitoring of progression for relapsed prostatic carcinoma
      after primary treatment is necessary, and early intervention recommended. This
      has now been made possible with rising prostate-specific antigen levels as an
      indication of the endpoint of treatment failure. Patients with relapsed disease
      can be divided into three groups: those relapsing following curative treatment
      with surgery or radiotherapy with local or distant metastases; patients who have
      been treated with primary hormonal palliative therapy or combination hormonal
      chemotherapy relapsing after the first palliative treatment, and patients
      relapsing after all acceptable therapies for the treatment of prostate cancer.
      The management of these groups of patients is discussed.

PMID- 7505235
TI  - Regulation of insulin-like growth factor binding protein secretion by a murine
      mammary epithelial cell line.
AB  - The regulation of insulin-like growth factor binding protein (IGFBP) secretion by
      mammogenic and lactogenic hormones was investigated in a mouse mammary epithelial
      cell line (COMMA-D/MME). Cells were grown to confluency on plastic culture plates
      in serum-containing medium. The confluent cells were exposed to the hormonal
      treatments in serum-free medium for 6 days. Conditioned medium was collected on
      Days 5 and 6 and analyzed for IGFBPs by 125I-labeled insulin-like growth factor
      (IGF)-II ligand blotting and quantified by densitometry. IGFBP data were
      expressed as absorbance units x millimeters (AUxmm) that were corrected for DNA
      per well. In basal serum-free media, the COMMA-D/MME cells secreted predominantly
      IGFBP-3, but also some IGFBP-2. The mammogenic growth factors, IGF-I (13.3 nM)
      and epidermal growth factor (EGF; 1.7 nM), both stimulated DNA synthesis (P <
      0.05); however, their effects on IGFBP-3 secretion differed. IGF-I stimulated
      IGFBP-3 secretion whereas EGF was inhibitory. In addition, EGF inhibited IGFBP-2
      secretion and IGF-I tended to increase it. No interaction was observed between
      IGF-I and EGF for any of the parameters measured. Three lactogenic hormones
      (insulin, 154 nM; prolactin, 4.3 nM; and cortisol, 1.4 microM) in all
      combinations were tested to determine their effects on IGFBP secretion. Insulin
      stimulated IGFBP-3 secretion and DNA synthesis, but had no effect on IGFBP-2
      secretion. Cortisol inhibited IGFBP-3 secretion and DNA synthesis, but increased
      IGFBP-2 secretion. Prolactin had no effect on any of the parameters examined. In
      summary, the COMMA-D/MME cells secrete IGFBP-2 and IGFBP-3 in serum-free media.
      Although the secretion of IGFBP-2 and IGFBP-3 in serum-free media. Although the
      secretion of IGFBP-2 and IGFBP-3 was regulated by several of the hormones and
      growth factors tested, no clear distinction was observed between the mammogenic
      and lactogenic treatments.

PMID- 7505236
TI  - Characterisation of an epitope recognised by a monoclonal antibody against horse
      alcohol dehydrogenase using peptides synthesised on solid support.
AB  - Immunological analysis, using the Pepscan technique, of the tetradecapeptide,
      Pro344-Glu357 (PLITHVLPFEKINE), from horse liver alcohol dehydrogenase has
      identified a five amino acid sequence, HVLPF, which binds a monoclonal antibody.
      The epitope seems to be rather flexible with only two of the amino acids, Pro and
      Phe, having the characteristics of contact residues. However, the presence of the
      adjacent glutamic acid residue as part of the Pepscan peptide has a dramatic
      negative neighbourhood effect and inhibits binding. This highlights the potential
      risk of missing an epitope altogether when using the Pepscan procedure for
      epitope mapping.

PMID- 7505237
TI  - Epitope mapping of a monoclonal antibody which binds HIV-1 Gag and not the Gag
      derived proteins.
AB  - Monoclonal antibody (MAb) 1G12 binds the uncleaved HIV-1 Gag polypeptide (p55),
      but fails to recognize the final products of the proteolytic processing [Sarubbi,
      E. et al. (1991) FEBS Lett. 279, 265-269]. In this report we show that binding of
      MAb 1G12 to a 110-residue Gag fragment containing the p17-p24 cleavage site
      prevents proteolysis of this site by the HIV-1 protease. Competition studies with
      synthetic peptides have been performed to map the binding site of MAb 1G12 on
      Gag. The antibody recognizes a sequential epitope that spans the HIV-1 protease
      cleavage site; determinants located on both p17 and p24 are required for antibody
      binding. MAb 1G12 is also shown to lack any cross-reactivity with other HIV-1
      protease cleavage sites.

PMID- 7505238
TI  - Interleukin 4 inhibits the production of some acute-phase proteins by human
      hepatocytes in primary culture.
AB  - Interleukin 4 (IL4) has been shown to exhibit anti-inflammatory effects by
      inhibiting the secretion by monocytes of proinflammatory cytokines such as
      interleukin 1 (IL1), interleukin 6 (IL6), and tumor necrosis factor (TNF) and by
      inducing the secretion of the IL1 receptor antagonist. We investigated the role
      of this cytokine on the production of acute-phase proteins in primary human
      hepatocyte cultures. Cells were exposed to either IL4 and/or IL6, the most potent
      mediator of hepatic acute phase proteins. IL4 led to decreased production of
      haptoglobin, C-reactive protein and albumin while alpha 1-antitrypsin and
      fibrinogen remained unaffected. These inhibitory effects of IL4 were also
      observed at the mRNA level. In addition, IL4 inhibited the IL6-induced production
      of haptoglobin although it had no effect on the induced C-reactive protein and
      fibrinogen. Our results demonstrate that IL4 can affect the production of a
      subset of acute-phase proteins by human hepatocytes and can antagonize some of
      the effects of IL6. These observations reinforce the notion that IL4 can be
      considered as an anti-inflammatory cytokine.

PMID- 7505239
TI  - The influence of 4 degrees C storage on proliferative potential of human bone
      marrow CD34+ cells. Transplantological implications.
AB  - The possibility of storage of human bone marrow CD34+ cells at 4 degrees C was
      investigated for bone marrow transplantational purposes. The cells were placed in
      Iscove medium supplemented with 20% serum (15% bovine calf serum 5% human AB
      serum) for three weeks at 4 degrees C. During the storage time, clonogenecity of
      granulocyto-monocytic (CFU-GM) erythropoietic (BFU-E) and megakaryocytic (CFU
      Meg) progenitors was investigated. It was found that it is possible to keep human
      CD34+ cells at 4 degrees C, at least for a few days before transplantation. At
      day four of the storage, the number of CFU-GM and BFU-E cells still exceeded 50%
      of the cells present at day 0. However, we have found that CFU-Meg in comparison
      to other progenitors are much more sensitive to metabolic storage stress. This
      enhanced sensitivity of megakaryocytic progenitors could explain, at least
      partially, the well known phenomenon of retardation of the thrombopoietic
      recovery in patients undergoing bone marrow transplantations.

PMID- 7505240
TI  - Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung
      fibrosis induced by bleomycin.
AB  - It was found that the BCG vaccine injected subcutaneously to the rats enhances
      the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this
      vaccine results in accumulation of activated macrophages in lung interstitium and
      in the bronchoalveolar spaces. It may be suggested that the activated macrophages
      release various cytokines which may stimulate the proliferation of fibroblasts
      and biosynthesis of extracellular matrix components.

PMID- 7505241
TI  - [Antithyroid drug-induced agranulocytosis: special reference to normal white
      blood cell count agranulocytosis].
AB  - This retrospective study was aimed at establishing the importance of the
      leukocyte differentiated count and not only routine white blood cell count in
      patients treated with antithyroid drug. From 1975 to September 1992, 77 patients
      with antithyroid drug-induced agranulocytosis were examined. In 12 patients
      (15.6%), the total white blood cell (WBC) count was greater than 3000/mm3. Eight
      of them showed a downward trend in their leukocyte counts (3000-4000/mm3).
      Consequently, granulocyte counts were measured. Two of the 12 patients had
      "symptomatic" agranulocytosis detected after the occurrence of infection. Because
      antithyroid drug-induced agranulocytosis was strongly suspected, granulocyte
      counts were checked. In the remaining two patients, the total WBC count was
      5700/mm3 and 5900/mm3, respectively. One was hospitalized to receive thyroid
      surgery. Although she was asymptomatic, agranulocytosis was unexpectedly detected
      on a routine preoperative examination. The other was diagnosed as agranulocytosis
      by routine WBC and granulocyte count monitoring since June 1989. Correct
      diagnosis was based on the leukocyte differentiated counts. We concluded that the
      leukocyte differentiated count and not only routine white blood count was
      critically important for the correct diagnosis of antithyroid drug-induced
      agranulocytosis in patients with Graves' disease.

PMID- 7505242
TI  - [Abnormal secretory response to verapamil of pancreatic B cells of neonatal rats
      maintained in high glucose].
AB  - The effect of verapamil on insulin secretion in the presence of IBMX was studied
      in B cells in pancreatic monolayer cultures of the neonatal rat using a
      perifusion system. For the initial three days, B cells were exposed to a medium
      of either 5.5 or 11.1 mM glucose and 10 microM iodoacetic acid (IAA) after which
      they were exposed to a medium of either 5.5 or 11.1mM glucose until day 7.
      Insulin secretion of B cells in medium of 5.5mM glucose (day 7) was not affected
      by IBMX, and the observations showed that verapamil significantly suppressed the
      secretion of insulin. However, the second phase of secretion was significantly
      increased by verapamil and IBMX. In contrast, insulin secretion of B cells
      exposed to a medium of 11.1mM glucose (day 7) showed similar trends, but the
      second phase secretion was increased further by verapamil in the presence of
      IBMX. The total amount of secretion was 2.3 times (125.5ng/ml) the secretion of
      cells exposed to low concentration of glucose (day 7). These results show that
      there is a possibility that in the presence of IBMX, verapamil, which is known to
      be a Ca2+ channel antagonist, shows the action of a Ca2+ channel agonist and
      promotes the secretion of insulin. Moreover, there were indications that a high
      concentration of glucose in culture affects functional maturation and functional
      differentiation of pancreatic B cells of neonatal rats and impairs the intra
      cellular signal transduction system.

PMID- 7505243
TI  - A new transgenic mouse model of chronic hyperglycemia.
AB  - Expression under the control of the mouse transferrin promoter of a transgene
      encoding a soluble secreted derivative of the ectodomain of the human insulin
      receptor in transgenic mice results in the accumulation of this high-affinity
      insulin-binding protein in the plasma. Alterations of glucose homeostasis are
      observed including postabsorptive hyperglycemia concomitant with increased
      hepatic glucose production and hyperinsulinemia. Thus, this is the first
      transgenic animal model of chronic hyperglycemia with alterations in glucose
      homeostasis that are produced without a targeted alteration of pancreatic
      function. These mice provide a new experimental model to follow the progression
      and long-term consequences of chronic hyperglycemia.

PMID- 7505244
TI  - GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine
      syndrome type I recognize different epitopes.
AB  - Glutamic acid decarboxylase (GAD) is a major islet cell autoantigen in insulin
      dependent diabetes mellitus (IDDM), and autoantibodies are found in high
      frequencies in patients with recent-onset IDDM, stiff-man syndrome (SMS), and
      autoimmune polyendocrine syndrome type I (APS I). Antigens in autoimmune
      disorders are often enzymes, and autoantibody binding frequently inhibit their
      activity. In this study, we examined the reactivity of anti-GAD-containing sera
      from 7 patients with IDDM, 4 patients with SMS, and 5 patients with APS I. All
      sera immunoprecipitated GAD from [35S]methionine-labeled rat islet lysates and
      the sera from patients with SMS and APS I, but none of the IDDM patients' sera,
      identified the GAD protein in Western blots. Two of four SMS patients' sera and 5
      of 5 APS I patients' sera, in contrast to 0 of 7 IDDM patients' sera, inhibited
      the enzymatic activity of GAD. When the various sera were tested with the GAD65
      and GAD67 isoforms, produced separately by transient expression in COS cells, the
      enzymatic activity of GAD65 was inhibited by sera from patients with SMS and APS
      I, whereas no effect on the GAD67 activity was observed. Taken together, the
      results demonstrate that the GAD autoantibodies in these three disorders display
      marked differences in epitope recognition and indicate that, during the
      development of the diseases, the autoantigen is being presented to the immune
      system through separate pathogenetic mechanisms.

PMID- 7505245
TI  - ADP ribosylation by cholera toxin identifies three G-proteins that are activated
      by the galanin receptor. Studies with RINm5F cell membranes.
AB  - Inhibition of insulin secretion by galanin is pertussis toxin (PTX) sensitive,
      suggesting the activation of one or more heterotrimeric (alpha, beta, gamma) G
      proteins (Gi/Go). Multiple effectors, including the K+ATP and L-type Ca2+
      channels, adenylyl cyclase, and an as yet unidentified system at a site close to
      exocytosis, are modulated by galanin. Therefore, it is necessary to delineate the
      particular G-proteins activated by the galanin receptor as a first step to
      understanding its net cellular response. During specific conditions, cholera
      toxin (CTX) can ADP-ribosylate the alpha i/alpha o-subunits of the PTX-sensitive
      substrates but only during receptor/G-protein interaction. Therefore, we used CTX
      catalyzed ADP ribosylation to identify galanin receptor-associated G-protein
      alpha-subunits in RINm5F cells. Galanin enhanced the ADP ribosylation of membrane
      proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) in two bands at 39,000 and 42,000 M(r). This labeling was blocked in
      membranes prepared from PTX-treated cells, enhanced by Mg2+, and showed a
      biphasic dependence on exogenous guanine nucleotides. Identification of the CTX
      ADP-ribosylated G-proteins by immunoprecipitation with selective antisera
      indicate activation by the galanin receptor of alpha i1 and alpha i3, which have
      the same mobility on SDS-PAGE (42,000 M(r)), and alpha i2 (39,000 M(r)). These
      studies provide evidence for the activation of multiple G-proteins by receptors
      for galanin in RINm5F cells.

PMID- 7505246
TI  - Comparison of Kodachrome to Polachrome: an alternate 35 mm color slide system
      with rapid processing capabilities.

PMID- 7505247
TI  - Voltage-activated ionic currents in goldfish pituitary cells.
AB  - The release of gonadotropin and growth hormone from goldfish pituitary cells has
      been shown to be dependent on the entry of extracellular Ca2+ through voltage
      sensitive Ca2+ channels by pharmacological studies. As a first step to further
      investigate the involvement of voltage-dependent ion channels in the regulation
      of anterior pituitary hormone release in the goldfish, cell excitability and
      voltage-dependent ion currents were characterized using tight-seal whole-cell
      recordings in dispersed goldfish pituitary cells. Cultured goldfish pituitary
      cells had an average membrane potential of -36 +/- 3 mV. When held at membrane
      potentials more negative than -60 mV, these cells were excitable, responding to
      depolarizing current pulses or anode break with the firing of single action
      potentials. Results from total current voltage-clamp recordings suggested that
      all goldfish pituitary cells possess voltage-dependent Na+, Ca2+, and K+
      currents. These currents were further characterized independently under isolated
      current recording conditions. The rapid, transient Na+ current activated at
      voltages more positive than -40 mV and was sensitive to tetrodotoxin. The steady
      state inactivation of this Na+ current was also voltage-dependent; at the
      measured resting potential, > or = 50% of the Na+ current was not available for
      activation. The voltage-dependence and activation kinetics of the
      tetraethylammonium-sensitive K+ current resembled those of the delayed rectifier
      K+ current. The K+ current activated slowly at potentials more positive than -40
      mV, and showed little inactivation over the duration of a 1-sec depolarizing
      pulse. Steady-state inactivation characteristics indicated that < 50% of the K+
      current was inactivated at resting potentials. Experiments with 4-aminopyridine
      indicated the presence of an early transient K+ current that activated in a
      similar voltage range as the delayed rectifier current. Using barium as the
      charge carrier to measure Ca2+ currents, a high-voltage activated, long-lasting
      Ca2+ current was revealed. This "L-type" Ca2+ current activated at potentials
      more positive than -30 mV and was inhibited by verapamil and nifedipine. This
      study indicates that goldfish pituitary cells possess the electrophysiological
      properties required for the participation of voltage-sensitive ion channels in
      the regulation of hormone release.

PMID- 7505248
TI  - 16S rDNA analysis reveals phylogenetic diversity among the polysaccharolytic
      clostridia.
AB  - Small subunit rDNA sequences were determined for 13 mesophilic,
      polysaccharolytic, mainly cellulolytic species of the genus Clostridium and one
      cellulolytic Eubacterium species. Sequences were compared to those of 36
      representatives of mesophilic and thermophilic clostridia, including those of
      nine thermophilic polysaccharolytic species published previously. The majority of
      strains group with 23S rRNA clusters I and III, while the others group with the
      thermophilic polysaccharolytic clostridia, i.e. C. stercorarium, C.
      thermolacticum and C. thermocellum. Lack of close genetic relationships between
      the various polysaccharolytic species is unexpected and may indicate that these
      biotechnologically important organisms differ with respect to the enzymology of
      polysaccharolytic degradation as well.

PMID- 7505249
TI  - Structural organization of the genes encoding human and murine FK506-binding
      protein (FKBP) 13 and comparison to FKBP1.
AB  - FK506-binding protein (FKBP)12 and FKBP13 are members of a family of proteins
      which bind the immunosuppressant drugs, FK506 and rapamycin. FKBP12 and FKBP13
      are encoded by distinct genes, designated FKBP1 and FKBP2, respectively. The
      structure of human FKBP1 was previously characterized. We now report the genomic
      structure of the human and murine FKBP2 genes. Comparison of FKBP1 and FKBP2
      reveals significant homology and correlation of intron positions in the C
      terminal region, suggesting that these genes may have evolved from a common
      ancestral gene.

PMID- 7505250
TI  - Organization of the gene encoding mouse vitronectin.
AB  - The gene (Vn) encoding the mouse vitronectin was isolated and its nucleotide
      sequence determined. The gene covers approximately 3 kb of genomic DNA. Alignment
      of the genomic sequence with that of the cDNA revealed that Vn consists of eight
      exons, interrupted by seven introns ranging in size from 78 to 723 bp.

PMID- 7505251
TI  - Secretion of insulin-like growth factor binding proteins (IGFBPs) by a rat
      pituitary tumour cell line.

PMID- 7505252
TI  - Molecular determinants of insulin action.
AB  - Insulin rapidly stimulates tyrosine phosphorylation of a 185-kDa protein in most
      cell types. This protein, insulin receptor substrate 1 (IRS-1), has been
      implicated as the first postreceptor step in insulin signal transmission based on
      studies with insulin receptor mutants. In cell culture and in vitro,
      phosphorylated IRS-1 associates with the lipid-metabolizing enzyme
      phosphatidylinositol 3-kinase (PI 3-kinase), resulting in activation of this
      enzyme. Thus, the insulin receptor, IRS-1 and PI-3 kinase represent three of the
      earliest steps in insulin action at the cellular level. We have recently
      demonstrated that insulin is capable of stimulating PI 3-kinase activity in liver
      and muscle in vivo in animals and that IRS-1 phosphorylation may play a
      significant role in the association/activation with PI 3-kinase in vivo.

PMID- 7505253
TI  - Dental evidence for the peopling of the New World: some methodological
      considerations.
AB  - Turner (1985b) and Greenberg et al. (1986) proposed that New World populations
      originated in northern Asia and entered the Americas in three migratory waves:
      Macro-Indian, Aleut-Eskimo, and Na-Dene. Biological support for this model comes
      from Turner's unweighted pair group (UPGMA) cluster analysis of discrete dental
      traits in world populations. Unfortunately, UPGMA analysis often creates suspect
      clusters and may not be valid as a method for displaying evolutionary
      relationships because it assumes that rates of evolution are equal among all
      populations. To test whether Turner's results are an artifact of his analytical
      method, I analyzed his published data (Turner 1985b) using two alternative
      techniques that do not assume homogeneous rates of change: a Wagner distance
      algorithm employing the Fitch-Margoliash criterion for goodness of fit and a
      maximum parsimony analysis using segment-coded dental trait frequencies. Both
      alternative methods produce trees that are similar to the UPGMA analysis results,
      supporting Turner's original results and basic conclusions. Comparisons of tree
      topology demonstrate that there is strong congruence between trees produced by
      all three methods, although the placement of certain populations, such as Na
      Dene, depends on the method of analysis employed.

PMID- 7505254
TI  - Complement regulatory proteins in early human fetal life: CD59, membrane co
      factor protein (MCP) and decay-accelerating factor (DAF) are differentially
      expressed in the developing liver.
AB  - The human fetus appears to be capable of protecting itself from maternal
      complement (C) from an early stage in development by expressing the C regulatory
      proteins decay-accelerating factor (DAF), membrane co-factor protein (MCP) and
      CD59 on fetally derived trophoblast at the feto-maternal interface. In this study
      we have examined the ontogeny of these proteins within the fetus itself and have
      focused on the liver which represents a major site of haemopoiesis during
      development. Immunostaining revealed that DAF, MCP and CD59 are all expressed
      from at least 6 weeks of gestation in the liver but that these proteins display
      distinct distribution patterns. CD59 was broadly distributed both within the
      epithelial and haemopoietic compartments, but expression of C3 convertase
      regulators was more restricted. DAF expression was limited to isolated cells
      within haemopoietic nests and the epithelium was DAF-negative. Although MCP
      expression on haemopoietic cells was also limited, by contrast with DAF the
      developing hepatic epithelium was strongly MCP-positive. Typical CD59 and MCP
      components were observed in fetal liver extracts by immunoblotting, although
      liver MCP components consistently migrated 4000-5000 MW ahead of those observed
      on placental trophoblast. Differences in the distribution of these proteins were
      also observed between the fetal and adult liver. In particular, by comparison
      with fetal hepatic epithelium, there was an apparent loss of MCP expression from
      adult hepatocytes. Thus, MCP appears to be developmentally regulated in the human
      liver and is expressed in the absence of DAF on the early hepatic epithelium.
      Overall, this study suggests that C regulatory proteins, and in particular CD59
      and MCP, are required from the very early stages of gestation within the fetus
      itself.

PMID- 7505255
TI  - Stimulation of antigen-specific T- and B-cell memory in local as well as systemic
      lymphoid tissues following oral immunization with cholera toxin adjuvant.
AB  - In the present study we investigated immunological memory at the cellular level
      following oral immunization using cholera toxin (CT) as the mucosal adjuvant. We
      found that memory cells, isolated from mice orally primed with keyhole limpet
      haemocyanin (KLH) admixed with CT adjuvant 8 months earlier, responded by
      increased proliferation to antigen-challenge in vitro. In contrast, unstimulated
      memory cells or KLH-stimulated cells from naive mice did not respond. Memory
      cells were isolated from different lymphoid tissues; spleen (SP), mesenteric
      lymph nodes (MLN), Peyer's patches (PP) as well as the intestinal lamina propria
      (LP). Thus, oral immunization using CT adjuvant promoted the generation of memory
      cells that were present in both systemic and local intestinal lymphoid tissues.
      The demonstration of lymphokine production in the KLH-responsive cultures
      indicated the presence of antigen-specific memory T cells. Lymphokine production
      early in culture was dominated by interleukin-2 (IL-2), which peaked on day 2-3,
      followed by IL-5 and, in particular, interferon-gamma (IFN-gamma) which increased
      over time. Lamina propria memory cells were found to proliferate poorly to recall
      antigen in vitro compared to lymphocytes from SP or MLN. In contrast, very
      significant production of IL-5 and, in particular, IFN-gamma was demonstrable in
      LP cell cultures. The use of CT adjuvant also stimulated the generation of
      antigen-specific memory B cells following oral immunization. This was evidenced
      by KLH-specific antibody production in antigen-challenged memory lymphocyte
      cultures. The memory B cells produced IgM anti-KLH, while no detectable antigen
      specific IgG or IgA was found. Unstimulated memory cells or naive cells failed to
      produce anti-KLH antibodies. These in vitro findings provide evidence that oral
      immunization using CT adjuvant stimulates both antigen-specific memory T and B
      cells. Furthermore, our data suggest the existence of memory B cells following
      oral CT adjuvant immunization which have retained the ability to produce IgM and
      which therefore probably have not undergone terminal isotype switch
      differentiation to other isotypes and thus have not deleted the mu constant heavy
      chain gene. Finally, our data also suggest that memory T and B cells, either
      sessile in the various lymphoid tissues or recirculating, can be activated by
      antigen in situ in, for example, lymph nodes and spleen and, more importantly, in
      the intestinal LP itself.

PMID- 7505256
TI  - Mapping major and minor T-cell epitopes in vitro and their immunogenic or
      tolerogenic effect in vivo in non-human primates.
AB  - The immunogenicity of synthetic peptides of in vitro mapped T- and B-cell
      epitopes from a Streptococcus mutans cell-surface antigen were investigated in
      non-human primates. Peptide (1-15) contains T-cell (7-15) and B-cell (8-13)
      epitopes, but is only immunogenic if dimerized (1-15)2 or linked to the carrier
      tetanus toxoid (1-15)TT. Monomers and dimers of T- and B-cell epitopes were
      prepared and used to immunize macaques. Immunogenicity was assayed in lymphocytes
      by the uptake of [3H]thymidine and serum antibodies by a solid-phase
      radioimmunoassay. Macaques immunized with the dimerized (1-15)2 or carrier-linked
      peptide (1-15)TT exhibited in vitro T-cell proliferative responses to peptides (1
      15) and (7-15). T cells from animals immunized with peptides (1-15), (7-15) or (7
      15)2 failed to elicit an immune response. In order to establish if these non
      immunogenic peptides might induce tolerance, the same macaques were challenged
      with the immunogenic peptide (1-15)TT. The results suggest that T-cell responses
      to peptide (1-15) were reestablished, but instead of responding to peptide (7-15)
      they were stimulated by a hitherto silent epitope (1-7). Tolerance to the major T
      cell epitope (7-15) and the expression of a minor (silent) T-cell epitope (1-7)
      was associated with B-cell tolerance, suggesting that T-cell help for antibodies
      resides in the major T-cell epitope (7-15). However, short-term T-cell lines
      revealed T-cell responses to peptides (1-7) and (7-15) in both tolerized and
      immunized macaques, but the relative frequency of the minor epitope (1-7)
      reactive lines was significantly higher in tolerized animals, whilst that for the
      major epitope (7-15) was higher in immunized animals. These findings suggest that
      the silent epitope (1-7) is really cryptic, in that it can be detected if the
      cell lines are first expanded in vitro with the whole peptide (1-15) and then
      stimulated with the truncated peptides (1-7) or (7-15). The results are
      consistent with the concept of a hierarchy of major and minor T-cell epitopes,
      now demonstrated in non-human primates, in which tolerance to the major T-cell
      epitope is associated with tolerance to antibody formation and the emergence of a
      minor T-cell epitope.

PMID- 7505258
TI  - B7/CD28 but not LFA-3/CD2 interactions can provide 'third-party' co-stimulation
      for human T-cell activation.
AB  - The requirement for co-stimulation in T-cell activation has become firmly
      established, whilst the precise identity of the molecules involved remains
      uncertain. Some of the major co-stimulatory molecules include ICAM-1, LFA-3 and
      B7. We have investigated the abilities of both LFA-3 and B7 to co-stimulate T
      cell proliferation under a number of conditions using transfected Chinese hamster
      ovary cells. Using anti-CD3 antibodies we observed that B7 but not LFA-3
      transfectants were capable of co-stimulating proliferation in purified peripheral
      blood T cells. In addition, both LFA-3 and B7 could induce proliferation in
      response to phytohaemagglutinin (PHA) and we obtained additive effects using both
      B7 and LFA-3 together. Using the superantigen staphylococcal enterotoxin B (SEB),
      we observed that presentation to purified T cells required the presence of class
      II-positive transfectants and that sensitivity to antigen was increased
      approximately 100-fold by the co-transfection of either B7 or LFA-3. However,
      when co-stimulatory molecules were provided by cells separate from those engaging
      the T-cell receptor (TcR), only B7 was capable of enhancing proliferation.
      Kinetic studies which investigated the time dependence for co-stimulation
      revealed that T cells responding to anti-CD3 antibodies required the B7 co
      stimulation within the first few hours, for proliferation to be effective. Our
      data differentiate between the co-stimulatory abilities of B7 and LFA-3 and
      support the concept of a pivotal role for B7 in T-cell proliferation.

PMID- 7505259
TI  - Monoclonal anti-idiotypes to herpes simplex virus type 1 capable of antigen
      specific priming & stimulatory activity.
AB  - Anti-idiotypic antibodies (Ab-2) to HSV-1 (herpes simplex virus 1) neutralizing
      monoclonal antibody were raised by hybridoma. These Ab-2 were found to represent
      an epitope of glycoprotein B (gB-1) of this virus. To further characterise this
      antibody for its ability to mimic the antigenic epitope, in vitro
      lymphoproliferation assays were done. In this assay (i) antigen specific
      lymphocyte priming activity of the three monoclonal Ab-2 and (ii) the in vitro
      stimulating ability of these Ab-2 for gb-1 primed mouse lymphocytes were tested.
      We could identify two monoclonal Ab-2 which were able to prime the mouse
      lymphocytes in vivo. These antibodies were able to recognise the in vitro
      stimulation signal of the antigen gB-1 and consequently could proliferate. The
      stimulation index was comparable to that with the antigen. These two Ab-2 were
      also recognized by the antigen primed mouse lymphocytes in a specific manner.

PMID- 7505257
TI  - Co-stimulation with B7 and targeted superantigen is required for MHC class II
      independent T-cell proliferation but not cytotoxicity.
AB  - The superantigen Staphylococcal enterotoxin A (SEA) conjugated to tumour-specific
      monoclonal antibodies (mAb) directs T cells to lyse tumour cells in the absence
      of major histocompatibility complex (MHC) class II. In contrast, the conjugate
      bound to MHC class II-negative tumour cells did not activate resting T cells to
      proliferate. The SEA-C215 mAb conjugate, when presented on the CA215 antigen
      expressing Colo205 cells, required either signalling with CD28 mAb or CHO cells
      expressing the natural CD28 ligand, B7, to activate the T cells. The CD28/B7 co
      stimulatory effect was further enhanced when the B7 and the tumour antigen were
      present on the same cell, decreasing the superantigen amount required for
      activation with a factor of 10(4). No influence of B7 was seen when the single
      CA215 or double CA215/B7 transfectants were used as targets for superantigen
      conjugate-dependent cytotoxicity. This suggests that the low affinity T-cell
      receptor (TcR) interaction of superantigen in the absence of MHC class II
      antigens is sufficient for induction of cytotoxicity but requires additional
      CD28/B7 signalling to result in proliferation of resting T cells.

PMID- 7505260
TI  - Variations in the ospB gene of Borrelia burgdorferi result in differences in
      monoclonal antibody reactivity and in production of escape variants.
AB  - An escape variant of Borrelia burgdorferi, selected with a monoclonal antibody to
      OspB, expressed a truncated form of OspB, the result of point mutations in the
      ospB gene leading to a premature termination codon. A single amino acid position
      in the C terminus of OspB was critical for monoclonal antibody recognition. The
      variations in the ospB gene suggest a mechanism for the evasion of the immune
      response by these organisms and may also have implications for current diagnostic
      and vaccine efforts.

PMID- 7505261
TI  - Acid phosphatase purified from Mycoplasma fermentans has protein tyrosine
      phosphatase-like activity.
AB  - Acid phosphatase purified from Mycoplasma fermentans dephosphorylated
      phosphotyrosine-containing lysozyme and Raytide, a peptide substrate for protein
      tyrosine phosphatases. The optimum pH for Raytide was about 5.5. Raytide
      phosphatase activity was inhibited by potassium fluoride, sodium molybdate, and
      sodium orthovanadate and was found to exist in some mycoplasmas.

PMID- 7505263
TI  - Sera of leprosy patients with type 2 reactions recognize selective sequences in
      Mycobacterium leprae recombinant LSR protein.
AB  - Type 2 reactions (erythema nodosum leprosum [ENL]) are episodic, reactional
      states causing significant morbidity in lepromatous leprosy patients. With a view
      to defining the immunological differences between the stable and reactional forms
      of lepromatous leprosy, we determined antibody responses to LSR, a recombinant
      protein of Mycobacterium leprae previously described by us (S. Laal, Y.D. Sharma,
      H.K. Prasad, A. Murtaza, S. Singh, S. Tangri, R. S. Mishra, and I. Nath, Proc.
      Natl. Acad. Sci. USA 88:1054-1058, 1991), as well as to 10- to 15-mer overlapping
      peptides synthesized on the basis of the LSR amino acid sequence. We report here
      the selective recognition of B cell epitopes by sera from patients with ENL as
      compared with a control group with nonreactional lepromatous leprosy. Peptides 2
      and 3, with the sequences GVTYEIDLTNKNAA and IDLTNKNAAKLRGD, respectively, were
      recognized by > 95% of sera from patients with active ENL. Peptide 3 in addition
      showed reactivity with sera taken from 91.6% of lepromatous leprosy patients who
      were apparently stable but who were recorded to have had ENL several weeks before
      or after the sample collection. The core sequence IDLTNKNAA common to both these
      peptides may be a major target of humoral responses in ENL. In addition, the RGD
      motif at the C terminus appeared to influence the antigenicity of peptide 3 in
      enzyme-linked immunosorbent assay. It would appear that humoral responses during
      ENL are directed to selective antigenic determinants of the leprosy bacillus. The
      use of such serological markers to identify lepromatous leprosy patients with a
      high risk for developing ENL would be of clinical and predictive value.

PMID- 7505262
TI  - Cloning and nucleotide sequence analysis of psaA, the Streptococcus pneumoniae
      gene encoding a 37-kilodalton protein homologous to previously reported
      Streptococcus sp. adhesins.
AB  - Gene psaA, which encodes the Streptococcus pneumoniae 37-kDa protein, was cloned
      in Escherichia coli, and its complete nucleotide sequence was determined.
      Analysis of the sequence of the 2.4-kb cloned fragment revealed three open
      reading frames (ORFs). ORF2, which is 933 bp long, was identified as psaA. The
      two other ORFs identified flank psaA. ORF1, located upstream of psaA, is 836
      nucleotides long and encodes a protein with a calculated molecular mass of 29,843
      Da. The sequence for ORF3, located downstream of psaA, was only partially
      determined. Northern (RNA) blot analysis of pneumococcal RNA suggests that psaA
      is transcribed as part of a polycistronic message. Analysis of the primary
      structure of the protein encoded by this gene indicated significant similarity to
      two previously reported streptococcal proteins, SsaB (80% similarity) and FimA
      (92.3% similarity), from S. sanguis and S. parasanguis, respectively. These two
      homologous proteins have been shown to be associated with bacterial adhesion, and
      the possibility of a similar role for PsaA is hypothesized.

PMID- 7505264
TI  - P-glycoprotein epitope mapping. I. Identification of a linear human-specific
      epitope in the fourth loop of the P-glycoprotein extracellular domain by MM4.17
      murine monoclonal antibody to human multi-drug-resistant cells.
AB  - A new murine monoclonal antibody (MAb), MM4.17, to human multi-drug-resistant
      (MDR) cells was found to be reactive in an ELISA with a synthetic 16-amino acid
      peptide selected from the fourth loop of the P-glycoprotein extracellular domain.
      Immunohistochemistry indicated that this MAb reacted in human tissues in the same
      pattern as that previously found with other human-specific MAbs to P
      glycoprotein. For a precise definition of the MM4.17 epitope, a peptide library
      consisting of overlapping 4- to 10-mer residues covering the entire P
      glycoprotein-fragment was synthesized on polyethylene pins and tested for MAb
      binding. The results of this ELISA demonstrated that the MM4.17 epitope is
      constituted by the continuous-linear TRIDDPET amino-acid sequence (residues 750
      757 of the human MDRI-P-glycoprotein). The MAb MM4.17 recognizes only the human
      MDRI-P-glycoprotein isoform, and excess TRIDDPET peptide blocks the binding of
      the MAb to MDR variants of CEM cells. These results demonstrate that the amino
      acid sequence TRIDDPET from the human MDRI gene represents the first continuous
      linear epitope identified in the P-glycoprotein extracellular domain.

PMID- 7505265
TI  - Expression pattern of breast-cancer-associated protein pS2/BCEI in colorectal
      tumors.
AB  - Recently, several carcinomas of the gastrointestinal tract were tested for
      pS2/BCEI activity, a gene isolated from breast-cancer cells and coding for a
      small secreted peptide. In the latter tumors, its activity is under estrogen
      control; surprisingly, it was also found expressed in carcinomas of the stomach,
      biliary tract and pancreas. We have now investigated the expression of this gene
      in 64 colorectal carcinomas, 31 adenomas and 13 polyps in comparison with their
      matrix tissues by applying molecular (RNA analysis) and immunohistochemical (pS2
      antibody) techniques. Positive pS2 immunostaining (ranging from focal to strong
      immunoreaction) was noted in 89% of human colon cancers, while 11% remained
      negative. Furthermore, all 40 transitional mucosae were strongly positive,
      whereas normal mucosa was negative. Of hyperplastic polyps, 68.2% displayed a
      significant immunoreaction, and 80.6% of adenomas were focally positive. Finally,
      6 out of 16 cases showed significant pS2 transcription in Northern blot analysis.
      These data clearly indicate that the breast-cancer-associated pS2 protein also
      plays an as yet undetermined role in the tumorigenesis of human colorectal
      carcinomas.

PMID- 7505266
TI  - Effect of ibuprofen and diclofenac on the chemotaxis induced by substance P and
      transforming growth factor-beta on human monocytes and polymorphonuclear cells.
AB  - The neuropeptide substance P and the cytokine transforming growth factor-beta are
      potent chemotactic factors for monocytes or polymorphonuclear cells. They are
      present in synovial fluid of arthritic patients, and participate in the
      pathogenesis of arthritis. We investigated, in vitro, the effect of two non
      steroidal anti-inflammatory drugs, ibuprofen and diclofenac, on the chemotactic
      effect of substance P and transforming growth factor-beta at concentrations that
      can be present in the synovial fluid of arthritic patients. Both drugs decrease
      the chemotaxis induced by substance P and transforming growth factor-beta, at
      concentrations that can be easily reached in the synovial fluid during therapy.
      This event could be involved in the effect of some non-steroidal anti
      inflammatory drugs on the development and progress of arthritic disease.

PMID- 7505267
TI  - Cerebrospinal fluid pharmacokinetics and toxicology of intraventricular and
      intrathecal arabinosyl-5-azacytosine (fazarabine, NSC 281272) in the nonhuman
      primate.
AB  - Arabinosyl-5-azacytosine (AAC), a new nucleoside antimetabolite, is broadly
      active in preclinical tumor screening evaluations. To assess the potential for
      intrathecal use of this drug, we studied the toxicity and pharmacokinetics of
      intrathecal and intraventricular administration in nonhuman primates. Four adult
      male rhesus monkeys were given single 10 mg intrathecal (n = 1) or
      intraventricular (n = 3) doses of AAC to determine its acute toxicity and
      pharmacokinetic parameters. An additional 3 animals were given four weekly 10 mg
      intrathecal doses to assess the systemic and neurologic toxicity associated with
      chronic administration. Disappearance from the cerebrospinal fluid (CSF) was
      biexponential, and CSF clearance was 0.2 ml/min, which exceeds the rate of CSF
      bulk flow by 5-fold. The peak CSF concentration and area under the concentration
      x time curve achieved with the intraventricular administration of 10 mg were one
      hundred, and fifty fold greater, respectively, than those achieved after an
      intravenous dose of 200 mg/kg (1500-2400 mg) in prior experiments. No clinically
      evident neurotoxicity was observed in either the single or the weekly x 4 dose
      groups. A slight, transient CSF pleocytosis and increased CSF protein was
      observed. Systemic toxicity was limited to one animal in the weekly x 4 dose
      group who demonstrated a mild and transient decrease in his peripheral leukocyte
      count unassociated with a change in his hematocrit or platelet count. These
      studies in nonhuman primates demonstrate a clear pharmacokinetic advantage for
      intrathecal vs systemic administration of AAC. This is demonstrated by a 50-fold
      greater CSF drug exposure with an intrathecal or intraventricular dose 1/200th of
      that which can be given systemically.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505268
TI  - Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD
      70, DOX-OXD).
AB  - Coupling of anthracyclines to high-molecular-weight carriers may alter drug
      disposition and improve antitumor effects. We have performed a clinical phase I
      trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered
      as single dose i.v. every 21-28 days. Thirteen patients have received a total of
      24 courses (median 2; range 1-3). At the starting dose of 40 mg/m2 doxorubicin
      equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO
      grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient
      with preexisting heart disease. Five patients were treated with 12.5 mg/m2 DOXeq.
      Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local
      phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO
      grade III) and WHO grade III vomiting in another patient. Subsequently, five
      patients received 20 mg/m2 DOXeq. Hepatotoxicity was noted in 5/5 patients (1 x
      WHO grade IV, 1 x WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 x
      WHO grade IV, 2 x WHO grade III). At 12.5 mg/m2 DOXeq, a patient diagnosed with a
      malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic
      analyses of total and free doxorubicin were performed in plasma and urine. The
      maximum peak plasma concentration (ppc) for total DOX was 12.3 micrograms/ml at
      40 mg/m2 DOXeq. The area under the plasma concentration time curve (AUC) ranged
      from 28.83-80.21 micrograms/ml*h with dose-dependent elimination half lives (t1/2
      alpha: 0.02-0.87 h; t1/2 beta: 2.69-11.58 h; t1/2 gamma: 41.44-136.58
      h).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505269
TI  - 5-Azacytidine (NSC 102816) in refractory germ cell tumors. A phase II trial of
      the Eastern Cooperative Oncology Group.

PMID- 7505270
TI  - The major acidic fibroblast growth factor (aFGF)-stimulated phosphoprotein from
      bovine liver plasma membranes has aFGF-stimulated kinase, autoadenylylation, and
      alkaline nucleotide phosphodiesterase activities.
AB  - The major acidic fibroblast growth factor (aFGF)-stimulated phosphoprotein (MAFP)
      purified from bovine liver exhibits kinase, autoadenylylation, and alkaline
      nucleotide phosphodiesterase activities depending upon reaction conditions. In
      the presence of divalent ions, MAFP showed intrinsic and a FGF-stimulated kinase
      activities (autophosphorylation) using either [gamma-32P]ATP or [gamma-32P]GTP as
      a substrate. The autophosphorylation activity of MAFP was stimulated at low
      concentrations of Ca2+, Mg2+, or Mn2+ (0.2-2 microM). Depletion of the divalent
      ions by EDTA abolished the autophosphorylation activity but enhanced the
      autoadenylylation activity of MAFP. [alpha-32P]ATP as well as [alpha-32P]NAD
      could serve as substrates for autoadenylylation activity of MAFP. aFGF appeared
      to enhance the autoadenylylation activity of MAFP with an optimal concentration
      (0.6-1.2 nM). P1, P3-di(adenosine-5')-triphosphate (AP3A) was found to be a
      potent inhibitor for the autophosphorylation and autoadenylylation activities of
      MAFP. Analyses by automated Edman degradation of the adenylylated and
      phosphorylated peptides derived from autoadenylylated and autophosphorylated MAFP
      revealed that both autoadenylylation and autophosphorylation occurred at residue
      Thr204. The kinase and autoadenylylation activities of MAFP had an optimal pH of
      6.9-7.4. However, at pH 8.9, MAFP showed intrinsic and aFGF-stimulated
      phosphodiesterase activities. aFGF appeared to stimulate the phosphodiesterase
      activity of MAFP without altering the Km (approximately 0.2 mM) of its substrate.

PMID- 7505271
TI  - A novel operon organization involving the genes for chorismate synthase (aromatic
      biosynthesis pathway) and ribosomal GTPase center proteins (L11, L1, L10, L12:
      rplKAJL) in cyanobacterium Synechocystis PCC 6803.
AB  - Many of the ribosomal protein (RP) genes in both bacterial and chloroplast
      genomes occur, for reasons not yet understood, in operons that include
      nonribosomal genes. Here we report such an operon organization in a
      cyanobacterium (Synechocystis PCC6803) involving the genes for four RPs that are
      important in the GTPase function of the ribosome and the aroC gene encoding
      chorismate synthase, a key enzyme in the shikimate pathway for biosynthesis of
      aromatic amino acids and cell wall components. The Synechocystis aroC encodes a
      362-amino-acid residue protein which is 52, 60, and 68% identical to two
      eubacterial (both 52%), yeast, and a higher plant (Corydalis) chorismate
      synthase, respectively. The gene was overexpressed in Escherichia coli, and the
      gene product was shown to cross-react with antibodies to Corydalis chorismate
      synthase; it also complemented an aroC-lacking E. coli strain. The Synechocystis
      rpl1 and rpl11 genes encode polypeptides of 237 and 141 amino acid residues,
      respectively, also with high sequence identities to the corresponding RP
      sequences from other eubacteria and higher plant chloroplasts. The gene order is
      shown to be: rpl11-86bp spacer-rpl1-460bp spacer-rpl10-87-bp spacer-rpl12-206bp
      spacer-aroC. Southern and Northern blot analyses of Synechocystis DNA and RNA,
      respectively, revealed a single cluster of these genes per genome which is
      transcribed from a common promoter to an unusually long, approximately 9500
      nucleotide transcript. Several constructs of the cyanobacterial aroC and rpl12
      genes were made and expressed in E. coli to examine the mechanisms for their very
      differential expression from a polycistronic mRNA (e.g. four copies L12/ribosome;
      chorismate synthase, a non-abundant protein). These results present the first
      biochemical/molecular genetic evidence of shikimate pathway in the cyanobacterial
      group.

PMID- 7505273
TI  - Migratory and proliferative effect of platelet-derived growth factor in rabbit
      retinal endothelial cells: evidence of an autocrine pathway of platelet-derived
      growth factor.
AB  - Angiogenesis is a crucial event in the progression of diabetic retinopathy.
      Migration and proliferation of endothelial cells (EC) are important steps in
      angiogenesis and are caused by angiogenic factors such as basic fibroblast growth
      factor (bFGF). In this work, capillary EC were isolated from rabbit retinal
      tissues and rabbit retinal EC (RREC) were found to secrete a migration factor for
      RREC in conditioned medium (CM). The activity was inhibited by an anti-platelet
      derived growth factor (PDGF) antibody, but not by an anti-bFGF antibody. We also
      found that RREC showed a migratory response to PDGF. The response was induced by
      PDGF-BB and PDGF-AB dose dependently, but not by PDGF-AA, indicating that it was
      mediated by PDGF-beta receptor-dependent pathways, and that the PDGF-like factor
      was PDGF-BB or -AB. In addition, PDGF-BB induced the proliferation of RREC as
      well as bFGF. These data indicate that RREC have an autocrine pathway of PDGF by
      the secretion of and the response to PDGF. PDGF may play significant parts in
      angiogenesis in the progression of diabetic retinopathy.

PMID- 7505272
TI  - Production of insulin-like growth factor binding proteins by human ovarian
      carcinoma cells.
AB  - Cells of the human ovarian carcinoma lines EFO-21, EFO-27, MFO-35 and MFO-36
      secrete binding proteins for insulin-like growth factors (IGFBPs) into their
      culture media. By sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS
      PAGE) and ligand blotting, seven groups of IGFBPs with molecular masses of 25, 30
      (doublet), 34, 37, 40, 45, and 50 kDa were observed, depending on the cell line
      under investigation. By Northern blot analyses using cDNAs or oligonucleotides
      specific for the six types of IGFBP (IGFBP-1 to IGFBP-6), mRNA for all IGFBPs
      tested except for IGFBP-1 could be detected in the ovarian carcinoma cell
      extracts. In detail, analysis of EFO-21 protein products by SDS-PAGE yielded
      IGFBPs of 25, 34, and 50 kDa; extracts of EFO-21 cells contained mRNAs for IGFBP
      2, -3, -4, and -6. EFO-27 cells produced IGFBPs of 40 kDa and 45 kDa as
      determined by SDS-PAGE, and mRNAs for IGFBP-3, -4, and -6 were detected. In the
      conditioned medium of MFO-35 cells, IGFBPs of 25, 30 (doublet), 34, 37, 40, and
      45 kDa were observed by SDS-PAGE, while mRNAs for the five proteins IGFBP-2 to
      IGFBP-6 were found. MFO-36 cells produced IGFBPs of 34 kDa and 50 kDa as
      determined by SDS-PAGE, and the cells expressed mRNAs for IGFBP-2, -3, -4, and 
      6. In relation to published molecular mass data of the known IGFBPs, the size of
      the secreted proteins could be correlated to the mRNA patterns expressed by the
      ovarian carcinoma cells. It is concluded that ovarian carcinoma cells frequently
      express IGFBP-3, -4, and -6 and, to a lesser extent, IGFBP-2; the expression of
      IGFBP-5 appears as a rather rare event, while IGFBP-1 was not found to be
      expressed in ovarian carcinoma cells.

PMID- 7505274
TI  - Transient mitochondrial transcript level decay in oxidative stressed
      chondrocytes.
AB  - Steady-state levels of 12S rRNA and NADH dehydrogenase subunit 4 mRNA (ND4)
      mitochondrial transcripts were measured on rabbit articular chondrocyte in
      culture. In pseudosynchronized chondrocytes, changes of mitochondrial RNA levels
      were observed during the progression of the cells in the cell cycle. Oxidative
      stress generated by the hypoxanthine-xanthine oxidase system (HX-XO) induced a
      transient decrease in the levels of both ND4 and 12S rRNA. Mitochondrial RNA
      levels recovered 24 h after the oxidative stress. These RNA level changes were
      not associated with modifications in the structure or the copy number of the
      mitochondrial genome. Furthermore, the decrease in the amount of the
      mitochondrial transcripts observed may be related to a transient inhibition of
      mitochondrial transcription since the treatment of cells with ethidium bromide (a
      mitochondrial transcription inhibitor) resulted in the same decrease in 12S rRNA
      level as HX-XO treatment alone.

PMID- 7505275
TI  - Calphostin-C stimulates epidermal growth factor receptor phosphorylation and
      internalization via light-dependent mechanism.
AB  - Calphostin-C with perylenequinone structure is known to bind the regulatory
      domain of protein kinase C (PKC) and to inhibit kinase activity in vitro in a
      light-dependent fashion. We have found that calphostin-C induces substantial
      serine and threonine phosphorylation of the epidermal growth factor (EGF)
      receptor in a light-dependent fashion in the EGF receptor-hyperproducing squamous
      carcinoma cell line NA. Tryptic phospho-peptide mapping and phospho-amino acid
      analysis revealed that calphostin-C-enhanced phosphorylation was on threonine
      669, serine 671, serine 1046/1047, and serine 1166. However, calphostin-C did not
      inhibit phosphorylation of the 80 K protein, a cytosolic major substrate of PKC
      (MARCKS). Staurosporine, a potent PKC inhibitor with affinity for the catalytic
      domain of PKC, inhibited phosphorylation of the 80 K protein and 12-O
      tetradecanoyl-13-phorbol acetate induction of EGF receptor phosphorylation but
      did not inhibit the calphostin-C induction of the EGF receptor phosphorylation.
      These results suggest that the target of calphostin-C in vivo is different from
      that of staurosporine and thus calphostin-C in vivo does not inhibit PKC.
      Furthermore, calphostin-C enhanced the internalization of phosphorylated EGF
      receptor. Thus, calphostin-C apparently activates a novel signal transduction
      pathway which involves phosphorylation and internalization of the EGF receptor
      via light-dependent mechanism.

PMID- 7505276
TI  - Upregulation of IGF1, IGF1-receptor, and late growth related genes in ventricular
      myocytes acutely after infarction in rats.
AB  - To determine the effects of acute myocardial infarction on the expression of
      insulin-like growth factor1 (IGF1) and insulin-like growth factor1 receptors (IGF
      1R) on the surviving myocytes of the left and right ventricles, large infarcts
      were produced in rats and the animals sacrificed 2 days later. Hemodynamic
      measurements of left and right ventricular pressures, +dP/dt and -dP/dt, and
      central venous pressure documented that coronary occlusion was associated with a
      severe impairment of cardiac function. By employing reverse transcriptase
      polymerase chain reaction (RTPCR), a low level of expression of IGF-1R mRNA was
      detected in myocytes from sham-operated rats. Acute myocardial infarction was
      found to enhance by nearly twofold the message for IGF-1R in viable myocytes
      biventricularly. Moreover, IGF1 mRNA increased 4.3-fold and 9.4-fold in left and
      right myocytes, respectively. In order to establish whether the upregulation of
      IGF1 and IGF-1R with infarction was coupled with induction of late growth related
      genes, which are known to be implicated in DNA replication and mitotic division,
      proliferating cell nuclear antigen (PCNA) and histone-H3 expression was assessed
      by Northern blot and RTPCR. The level of expression of PCNA mRNA was found to be
      increased 3.9-fold and 2.4-fold in left and right myocytes, respectively from
      infarcted hearts. Corresponding increments in histone-H3 mRNA were 25.5-fold and
      5.3-fold, respectively. However, PCNA protein as detected by immunoperoxidase
      staining was restricted to a limited number of myocyte nuclei adjacent to the
      necrotic myocardium of the left ventricle. In conclusion, acute myocardial
      infarction is associated with enhanced expression of IGF1 and IGF-1R on stressed
      myocytes, and this phenomenon may activate genes essential for DNA synthesis,
      possibly affecting myocyte growth. These processes may be fundamental for the
      reconstitution of tissue mass and amelioration of function after infarction.

PMID- 7505277
TI  - Alterations in the cyclic AMP signal transduction pathway regulating
      ribonucleotide reductase gene expression in malignant H-ras transformed cell
      lines.
AB  - Ribonucleotide reductase is a highly regulated activity responsible for reducing
      ribonucleotides to deoxyribonucleotides, which are required for DNA synthesis and
      DNA repair. We have tested the hypothesis that malignant cell populations contain
      alterations in signal pathways important in controlling the expression of the two
      genes that code for ribonucleotide reductase, R1 and R2. A series of radiation
      and H-ras transformed mouse 10T1/2 cell lines with increasing malignant potential
      were exposed to stimulators of cAMP synthesis (forskolin and cholera toxin), an
      inhibitor of cAMP degradation (3-isobutyl-1-methylxanthine) and a biologically
      stable analogue of cAMP (8-bromo-cAMP). Dramatic elevations in the expression of
      the R1 and R2 genes at the message and protein levels were observed in malignant
      metastatic populations, which were not detected in the normal parental cell line
      or in cells capable of benign tumor formation. These changes in ribonucleotide
      reductase gene expression occurred without any detectable modifications in the
      rates of DNA synthesis, showing that they were regulated by a novel mechanism
      independent of the S phase of the cell cycle. Furthermore, studies with forskolin
      (a stimulator of the protein kinase A signal pathway) and the tumor promoter 12-0
      tetradecanoylphorbol-13-acetate (a stimulator of the protein kinase C signal
      pathway), alone or in combination, indicated that their effects on R1 and R2 gene
      expression in a highly malignant cell line were greater than when they were
      tested individually, suggesting that the two pathways modulating R1 and R2 gene
      expression can cooperate to regulate ribonucleotide reduction, and interestingly
      this can occur in a synergistic fashion. Also, a direct relationship between H
      ras expression and ribonucleotide reductase gene expression was observed;
      analysis of forskolin mediated elevations in R1 and R2 message levels closely
      correlated with the levels of H-ras expression in the various cell lines. In
      total, these studies demonstrate that ribonucleotide reductase expression is
      controlled by a complex process, and malignant ras transformed cells contain
      alterations in the regulation of signal transduction pathways that lead to novel
      modifications in ribonucleotide reductase gene expression. This signal mechanism,
      which is aberrantly regulated in malignant cells, may be related to regulatory
      pathways involved in determining ribonucleotide reductase expression in a S phase
      independent manner during periods of DNA repair.

PMID- 7505278
TI  - Regulation of insulin-like growth factor binding protein synthesis and secretion
      in human retinal pigment epithelial cells.
AB  - Cultured human retinal pigment epithelial cells (RPE) secrete insulin-like growth
      factor binding proteins (IGFBPs), a family of polypeptides which modulate the
      actions of the insulin-like growth factors. RPE cells secrete two IGFBPs with Mr
      estimates of 34,000 and 46,000, respectively. Treatment of RPE cells with IGF-I
      markedly stimulated the secretion of the 46,000 Mr form. This stimulation
      occurred via an IGF-I receptor independent mechanism because both [QAYL]IGF-I (an
      IGF-I analogue with decreased affinity for the IGFBPs but normal affinity for the
      IGF-I receptor) and alpha-IR3 (a blocking monoclonal antibody against the IGF-I
      receptor) had no effect on IGF-I stimulated increases in IGFBPs. Additionally,
      [QAYL]IGF-I enhanced RPE cell proliferation to the same magnitude as IGF-I.
      Treatment with IGF-I, [QAYL]IGF-I, or alpha-IR3 had no effect on steady-state
      levels of the 2.5 kb IGFBP-3 or the 1.3 kb IGFBP-6 mRNA transcripts as measured
      by Northern blotting and quantitative autoradiography. Forskolin and a group of
      candidate growth factors, including platelet-derived growth factor, epidermal
      growth factor, and acidic and basic fibroblast growth factor, modestly increased
      IGFBP secretion when compared to untreated cells, but these effects were small
      when compared to IGF-I treatment. Fetal calf serum enhanced the presence of the
      2.5 kb IGFBP-3 mRNA transcript in a dose-dependent fashion but had no effect on
      the 1.3 kb IGFBP-6 mRNA transcript. IGF-I, forskolin, and the candidate growth
      factors had no effect on either IGFBP-3 or IGFBP-6 mRNA. These data suggest that
      the production of IGFBPs in human RPE cells is regulated by distinct mechanisms
      which include (1) an IGF-I receptor independent interaction of IGF-I with
      secreted IGFBPs and (2) de novo synthesis of IGFBPs by serum-containing factors.

PMID- 7505279
TI  - Induction by vasoactive intestinal peptide of interferon alpha/beta synthesis in
      glial cells but not in neurons.
AB  - Vasoactive intestinal peptide (VIP), a 28-amino acid peptide, plays a
      multifunctional neuromodulatory role in both peripheral and central nervous
      systems. We have recently reported that VIP induces interferon (IFN) alpha/beta
      synthesis in human colon adenocarcinoma cell line HT-29. It has been reported
      that VIP may counteract HIV-induced neuronal cell death; therefore, we postulated
      that the action of VIP may be mediated by a cascade regulation, involving the
      production of some cytokines such as IFN. Here we demonstrate that primary
      cultures of rat mesencephalic neurons and glial cells respond differently to VIP.
      Thus VIP enhanced 2'5' oligoadenylate (2'5' A) synthetase activity and inhibited
      vesicular stomatitis virus multiplication in glial cultures only. However, both
      cell cultures had functional adenylate cyclase coupled receptors for VIP. The
      increase in 2'5'A synthetase activity in glial cultures reached a maximum with
      10(-6) M VIP and required cellular RNA and protein synthesis. Anti-IFN
      alpha/beta, but not anti-IFN gamma, antibodies abolished the induction of the
      antiviral and 2'5'A synthetase activities by VIP in rat glial-enriched cultures,
      suggesting that these inductions were mediated through IFN alpha/beta synthesis.
      Moreover, VIP or poly (i). poly (C12U) caused, in the glial cultures, the
      induction and secretion of an IFN of type alpha/beta with a titer value of 16 and
      32 units/ml respectively. In contrast, neither of these two substances was able
      to induce IFN synthesis in neurons, which were, however, sensitive to IFN
      alpha/beta produced by VIP-treated glial cells. IFN produced by VIP in glial
      cells may therefore play an important role in defending the brain against
      viruses.

PMID- 7505280
TI  - Insulin-like growth factor-binding protein enhancement of insulin-like growth
      factor-I (IGF-I)-mediated DNA synthesis and IGF-I binding in a human breast
      carcinoma cell line.
AB  - The insulin-like growth factors (IGFs) are potent mitogens for malignant cell
      proliferation. The majority of secreted IGFs are bound to specific IGF-binding
      proteins (IGFBPs) that are secreted by a large number of cells. These proteins
      may either inhibit or enhance IGF actions. Breast carcinoma cells secrete a
      variety of IGFBPs. We have previously demonstrated that retinoic acid (RA)
      inhibition of IGF-I-stimulated MCF-7 cell proliferation is associated with
      increased IGFBP-3 levels in the conditioned media. We therefore investigated the
      effect of recombinant IGFBP-3 as well as IGFBP-2, -4 and -5 on IGF-I stimulation
      of DNA synthesis and IGF-I binding in the MCF-7 human breast carcinoma cell line.
      IGFBP-2 and -3 enhanced IGF-I stimulation of DNA synthesis in MCF-7 cells while
      IGFBP-4 and -5 had no effect. Transfection of MCF-7 cells with an IGFBP-3
      expression vector resulted in the enhanced secretion of IGFBP-3 with an
      accompanying increase in IGF-I binding as well as increased cell proliferation
      upon treatment of the cells with IGF-I. IGF-I preincubation of MCF-7 cells
      transfected with control pSVneo plasmids results in cells refractory to further
      IGF-I stimulation of thymidine incorporation while IGF-I continues to stimulate
      [3H]-thymidine incorporation in IGFBP-3-transfected MCF-7 cells, suggesting that
      IGFBP-3 protects the cells from IGF-I-mediated down regulation of its receptor.
      Therefore, IGFBP-3 secreted by MCF-7 cells can enhance IGF-I stimulation of DNA
      synthesis, increase IGF-I binding to these cells, and prevent IGF-I-induced
      desensitization of its own receptor, suggesting that IGFBP-3 plays a significant
      role in IGF-I-mediated breast carcinoma proliferation.

PMID- 7505281
TI  - Importance of nitric oxide synthase inhibition to the attenuated vascular
      responses induced by topical L-nitroarginine during vibrissal stimulation.
AB  - We assessed the regional cerebral blood flow (rCBF) response to vibrissal
      stimulation before and after nitric oxide synthase (NOS) inhibitors were
      topically applied through a closed cranial window placed over the cortical barrel
      fields in anesthetized Sprague-Dawley rats. In the presence of L-nitroarginine (1
      mM), both the maximum and total responses became reduced, but only in those
      animals demonstrating > 50% inhibition of NOS activity as determined by the
      conversion of [3H]arginine to [3H]citrulline within homogenates taken from
      cortical gray matter under the cranial window. The degree of enzyme inhibition
      depended in part, upon duration after topical application of NOS inhibitor. When
      > 50%, enzyme inhibition correlated with the decrease in maximum and total rCBF
      response (p < 0.01). These findings emphasize the merits of assessing enzyme
      activity after administering NOS inhibitors, and suggest that NO generated from
      parenchymal NOS activity plays an important role in the cerebrovascular response
      to physiologic somatosensory stimulation under the stated conditions.

PMID- 7505282
TI  - Major role of nitric oxide in the mediation of regional CO2 responsiveness of the
      cerebral and spinal cord vessels of the cat.
AB  - The role of nitric oxide (NO) in the mediation of cerebrovascular CO2
      responsiveness was studied in 10 distinct brain and spinal cord regions of the
      anesthetized, ventilated, temperature-controlled, normoxic cat. Regional CBF was
      measured with 15-micron radiolabeled microspheres in hypocapnic, normocapnic, and
      hypercapnic conditions. CO2 responsiveness of each region was determined from the
      equation of the best-fit regression lines to the obtained flow values. The effect
      of altered endothelial and/or neuronal NO synthesis on CO2 responsiveness was
      studied following either selective blockade of the NO synthase enzyme by N omega
      nitro-L-arginine methyl ester (L-NAME; 3 or 30 mg/kg i.v.) or simultaneous
      administration of L-NAME (3 mg/kg i.v.) and a large dose of the NO precursor L
      arginine (30 mg/kg i.v.). Blockade of NO synthesis by 30 mg/kg L-NAME resulted in
      a significant reduction of the steady-state regional blood flow values and in an
      almost complete abolition of the CO2 sensitivity in each region studied. Changes
      of the basal flow values as well as the reduction of the regional CO2 sensitivity
      were dose dependent. Hypothalamic, sensorimotor cortical, and cerebellar regions
      were the areas most sensitive to the NO blockade. Impaired CO2 responsiveness
      following NO synthase inhibition, however, was reversed in these regions by
      simultaneous administration of a large dose of intravenously injected L-arginine.
      These findings suggest a major role of nitric oxide in the mediation of regional
      cerebrovascular CO2 responsiveness in cats.

PMID- 7505283
TI  - Poly A-linked colorimetric microtiter plate assay for HIV reverse transcriptase.
AB  - An assay for detection of the reverse transcriptase (RT) of the human
      immunodeficiency virus (HIV) was developed using poly A linked to microtiter
      plate with colorimetric detection of incorporated biotin deoxyuridine
      triphosphate (biotin-dUTP). During the RT reaction, biotin-dUTP was incorporated
      into oligodeoxythymidylic acid (oligo-dT) which had been hybridized with poly A.
      At the detection step, horseradish peroxidase conjugated streptavidin was added,
      followed by the reaction of a colorimetric substrate for this enzyme. This method
      was contrasted with the two standard isotopic RT assays. There was excellent
      correlation between the colorimetric RT assay and each of two isotopic RT assays
      for both detection and quantification of avian myoblastosis virus reverse
      transcriptase (AMV-RT) and of HIV RT in human lymphocytes infected in vitro with
      HIV-1. The total assay required for performing the colorimetric assay, including
      the RT reaction, was 40 min.

PMID- 7505284
TI  - The Langat model for tick-borne encephalitis virus. Specific detection by RT-PCR.
AB  - We have developed a reverse-transcriptase polymerase chain reaction assay for
      rapid detection of Langat (LGT) virus, a flavivirus that is closely related to
      the highly pathogenic tick-borne encephalitis (TBE) viruses. Unlike TBE viruses,
      LGT virus exhibits a significantly lower virulence for man. The assay serves as a
      safe alternative for the development and optimization of specific assays for the
      highly pathogenic subtypes of TBE viruses that are endemic throughout much of
      Europe, the former Soviet Union, and China.

PMID- 7505285
TI  - Bluetongue virus: production and study of viral antigen for serological
      diagnosis.
AB  - A soluble antigen, produced from the culture supernatant of VERO cells infected
      with bluetongue virus serotype 4 (BTV-S4) and concentrated by sequential
      ultrafiltration with membranes with cut-off values 10(3) and 25 x 10(3) NMWP,
      showed complete identity to standard antigens when compared by agar gel
      immunodiffusion (AGID) and SDS-PAGE profiles, revealing that the main protein
      component responsible for the AGID reaction has a molecular weight of about 60
      kDa corresponding probably to the NS1 protein.

PMID- 7505286
TI  - Clinical features and endocrine status in patients with growth hormone
      insensitivity (Laron syndrome).
AB  - Twenty-seven patients with GH insensitivity were identified from 44 possible
      cases, using a scoring system based on height standard deviation score (SDS),
      basal GH, insulin-like growth factor-I (IGF-I), IGF-I response to IGF-I
      generation test, and GH-binding protein (GH-BP) determinations. The 27 cases were
      from 8 European countries and Australia. Clinical features were as follows: age
      2.8-22.6 yr; 12 male, 15 female, 19 prepubertal. Birth weight was median -0.72
      SDS (1.75(-)-3.29) and birth length, median -1.59 SDS (0.63(-)-3.63).
      Hypoglycemia had been documented in 33% of the cases, and micropenis was present
      in 58% of the males. At assessment, height was median -6.1 SDS (-3.8(-)-10.2),
      weight was median -3.2 SDS (-0.1 to -5.2), and percentage weight for height,
      median 111.3 (72-271). Puberty was absent in 2 boys aged 15 yr and in 3 girls
      aged 13 yr. Bone age was delayed in 19 of the 27 patients. Endocrine
      investigations showed basal serum GH median 17 micrograms/L (0.5-79), IGF-I
      values less than 5th percentile, and all except 2, age less than 8 yr, less than
      0.1 percentile for age. Percentage increment of IGF-I during IGF-I generation
      test (hGH 0.1 U/kg body weight daily x 4) did not exceed twice the intraassay
      coefficient of variation, being less than 0.1 percentile for age. IGF-II was
      median 135.0 micrograms/L (62-232), all values being less than 5th percentile for
      age. Insulin-like growth factor binding protein-3 (IGFBP-3) values were median
      0.53 mg/L (0.10-1.17 mg/L), all being less than 5th percentile for age. IGFBP-3
      values after hGH remained less than 5th percentile. IGFBP-1 values showed the
      normal fall with age, some being above the normal range; IGFBP-2 values were
      normal. There was a positive correlation between height SDS and IGF-II SDS (r =
      0.66, P < 0.001) and IGFBP-3 (r = 0.64, P < 0.001). Specific binding of [125I]hGH
      to GH-BP was undetectable in 18 patients and extremely low (< or = 5.6%) in 2. GH
      BP was normal (14.2-45.9% radioactivity) in 7 subjects, all female, demonstrating
      that normal GH-BP does not exclude GH insensitivity.

PMID- 7505287
TI  - The effect of dietary protein supplementation on insulin-like growth factors
      (IGFs) and IGF-binding proteins in children with shigellosis.
AB  - Nutrient deficiency causes growth failure and decreases serum insulin-like growth
      factor-I (IGF-I) concentrations. Because IGFBPs modulate the concentrations and
      availability of IGFs in serum, IGF-binding proteins (IGFBPs) were measured along
      with IGF-I and IGF-II before and after 21 days of refeeding in 22 undernourished
      Bangladeshi children (2-4 yr of age) with shigellosis. The effects of a 150
      Cal/kg.day diet with a normal protein (6%; n = 10) or high protein (15%; n = 12)
      content were studied. The results were compared with those of 25 age-matched
      healthy American children (controls). Body weight gain was better in patients
      receiving the high protein diet than in those receiving the normal protein diet.
      In both groups, initial IGF-I (32 +/- 6 and 24 +/- 7 ng/mL; mean +/- SD) and IGF
      II (177 +/- 15, 174 +/- 45 ng/mL) concentrations were low compared to controls
      (100 +/- 12 and 542 +/- 29 ng/mL, respectively; P < 0.007). After refeeding, IGF
      I increased to 160 +/- 26 ng/mL on the normal protein diet and to 322 +/- 41
      ng/mL on the high protein diet, exceeding values in controls (P < 0.007). IGF-II
      increased more than 2-fold on each diet (P < 0.007), reaching control values.
      IGFBP-2 concentrations before refeeding were twice those in controls (750 +/- 200
      vs. 317 +/- 33 ng/mL; P < 0.007) and normalized after refeeding in the high
      protein group (288 +/- 32 ng/mL; P = NS), but remained elevated in the normal
      protein group (526 +/- 77 ng/mL; P < 0.007). IGFBP-3 levels before refeeding were
      low and returned to normal on each diet. IGFBP-3 proteolytic activity in serum
      was initially increased and declined on the high protein diet. In conclusion,
      protein content in the refeeding diet differentially affects IGFs and IGFBPs in
      young undernourished children with infection. IGF-I and IGFBP-2 seem to be
      particularly sensitive to dietary protein alterations. We speculate that an
      increase in IGF-I concentrations, normalization of IGFBP levels, and a decrease
      in IGFBP-3 proteolytic activity in serum may all be involved in the improved
      recovery and catch-up growth observed with the high protein diet.

PMID- 7505288
TI  - Normative data for insulin-like growth factors (IGFs), IGF-binding proteins, and
      growth hormone-binding protein in a healthy Spanish pediatric population: age-
      and sex-related changes.
AB  - The normal values of insulin-like growth factors (IGFs) after extraction, their
      binding proteins, and the high affinity GH-binding protein are not well
      established in infancy or childhood. We report the relationship between serum IGF
      I, IGF-II, their binding proteins IGFBP-1 and IGFBP-3, and GH-binding protein in
      600 normal Spanish children who were divided into 5 groups according to Tanner
      stage: I, 150 males and 102 females; II, 40 males and 42 females; III, 45 males
      and 45 females; IV, 42 males and 55 females; and V, 23 males and 56 females.
      Serum IGF-I levels increase slowly during childhood in both sexes, exhibiting a
      dramatic increase during puberty and a significant decline [P < 0.001, by
      analysis of variance (ANOVA)] during adulthood. The pubertal peak occurs
      approximately 2 yr earlier in girls than in boys. In contrast, serum IGF-II
      levels remain stable throughout childhood, showing no pubertal peak. In boys,
      there is a significant decline in IGF-II levels during adulthood (P < 0.001).
      Serum IGFBP-3 levels show a pattern similar to that of IGF-I, with a significant
      increase during childhood and a significant decline during adulthood (P < 0.001,
      ANOVA) in both males and females. In contrast, serum IGFBP-1 levels decrease
      dramatically during childhood in both boys and girls (P < 0.001 and P < 0.005,
      respectively, by ANOVA). A significant decline in serum GH-binding protein levels
      is observed between prepubertal and pubertal children of both sexes (P < 0.001).
      There is a close linear correlation between the sum of serum IGF-I plus IGF-II
      levels vs. serum IGFBP-3 (r = 0.724; P < 0.0001). In contrast, there is a
      nonlinear correlation between serum IGF-I vs. serum IGFBP-3 (concave curve) as
      well as between serum IGF-II and serum IGFBP-3 (convex curve). A negative
      correlation was found between serum IGF-I vs. IGFBP-1 (r = -0.51; P < 0.0001) as
      well as between the sum of serum IGF-I plus IGF-II vs. IGFBP-1 (r = -0.47; P <
      0.0001), but not between serum IGF-II and IGFBP-1. These data emphasize that when
      these tests are performed in the clinic, their interpretation should be based
      upon age- and sex-specific criteria.

PMID- 7505289
TI  - The composition and distribution of insulin-like growth factors (IGFs) and IGF
      binding proteins (IGFBPs) in the serum of growth hormone receptor-deficient
      patients: effects of IGF-I therapy on IGFBP-3.
AB  - We have previously reported that adult GH receptor-deficient (GHRD) patients
      treated subcutaneously with recombinant human insulin-like growth factor (IGF)-I
      have increased serum IGF-I levels and decreased IGF-II levels, whereas IGF
      binding protein-3 (IGFBP-3) levels were unchanged. To further investigate the
      effects of IGF-I administration upon the IGF-IGFBP axis in GHRD, we have
      examined: 1) the molecular distribution of IGF-I and IGF-II among the IGFBPs; 2)
      the composition and distribution of the IGFBPs, in particular IGFBP-3; and 3) the
      acid labile subunit (ALS). Serum samples from adult GHRD patients who were
      treated sc with recombinant human IGF-I (40 micrograms/kg, sc, twice a day) or
      from normal Ecuadorian adults were incubated with [125I]IGF-II and subjected to
      neutral size-exclusion chromatography. The fractions were then subjected to
      Western ligand blot, Western immunoblot, IGFBP-3 RIA, and IGF RIAs. Serum of
      healthy adults incorporated [125I]IGF-II into the 150- and 44-kilodalton (kDa)
      IGFBP region. The 150-kDa IGFBP region contained most of the circulating IGFBP-3,
      whereas the 44-kDa IGFBP region contained mainly IGFBP-1, 2, and 4. The 150-kDa
      region also contained a unique 28-kDa immunoreactive form of IGFBP-3, which was
      not detectable by Western ligand blot. Endogenous IGF-I and IGF-II were
      distributed equally in the 150- and 44-kDa IGFBP regions. Sera from GHRD patients
      mainly incorporated [125I]IGF-II into the 44-kDa IGFBP region. Similar to control
      sera, the 150-kDa IGFBP region contained IGFBP-3, albeit at lower concentrations.
      The 44-kDa IGFBP region contained all IGFBPs including 50% of the total
      immunoreactive IGFBP-3. The two immunoreactive forms of IGFBP 3 (40- to 45-kDa
      doublet and 28-kDa band) were present in both IGFBP regions. The IGF size
      distribution study revealed that the 150-kDa IGFBP region carried half of the
      circulating endogenous IGF-I, but only 30% of the IGF-II. Concentrations of the
      ALS were consistently low. Administration of IGF-I to GHRD patients was unable to
      increase concentrations of the molecular forms of IGFBP-3, correct the aberrant
      distribution of IGFs among the IGFBPs, or increase serum concentrations of ALS.
      In conclusion, we have found two forms of IGFBP-3 associated with IGF and ALS,
      which are capable of forming the ternary 150-kDa complex in healthy adult serum.
      The ratio of these two forms of IGFBP-3 and their distribution in serum was
      different between GHRD and control patients.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7505290
TI  - The immunodominant region on human thyroid peroxidase recognized by
      autoantibodies does not contain the monoclonal antibody 47/c21 linear epitope.
AB  - We performed studies to determine whether the binding sites on thyroid peroxidase
      (TPO) of immunoglobulin antigen binding fragments (Fabs) representing more than
      80% of the human autoantibody repertoire overlap with the binding site of
      monoclonal antibody (Mab) 47, the only Mab whose partial epitope has been defined
      at the amino acid level (residues 713-721). We also investigated whether these
      Fabs preferentially recognize native or denatured TPO. None of the Fabs, when
      bound to radiolabeled TPO, interfered with the ability of Mab 47 to bind to this
      material. In enzyme-linked immunosorbent assay experiments, the binding of TPO
      autoantibody Fabs SP1.5, WR1.7, TR1.8, and TR1.9 was greatly diminished by
      denaturation of TPO. In contrast, binding of Mab 47 was higher to denatured TPO
      than to intact TPO. Our studies indicate that the Mab 47/C21 epitope lies outside
      the immunodominant region on TPO. Further, the data confirm that the majority of
      epitopes for TPO autoantibodies are highly conformational (dependent on the three
      dimensional structure of the native protein). Native TPO will be needed to
      complete the mapping of the epitopes for TPO autoantibodies as well as to
      determine the amino acids at the autoantibody-antigen-binding sites.

PMID- 7505291
TI  - Genotypic identification of mycobacteria by nucleic acid sequence determination:
      report of a 2-year experience in a clinical laboratory.
AB  - Clinical isolates of Mycobacterium spp. were identified by direct sequence
      determination of 16S rRNA gene fragments amplified by polymerase chain reaction.
      Identification was based on a hypervariable region within the 16S rRNA gene in
      which mycobacterial species are characterized by species-specific nucleotide
      sequences. A manually aligned data base including the signature sequences of 52
      species of mycobacteria easily allowed rapid and correct identification. The
      results of this study demonstrate that polymerase chain reaction-mediated direct
      sequence determination can be used as a rapid and reliable method for the
      identification of mycobacteria in the clinical laboratory. In addition, the
      prompt recognition of previously undescribed species is now feasible.

PMID- 7505292
TI  - Virological features of hepatitis C virus infection in hemodialysis patients.
AB  - The clinical and epidemiological relevance of circulating antibodies to hepatitis
      C virus (HCV) in hemodialysis patients is uncertain, since clinical signs of
      infection are often mild or absent, with alanine aminotransferase (ALT) values
      that are virtually always normal, and liver biopsies are only rarely performed.
      Determination of HCV RNA in serum is therefore critical for distinguishing
      chronic HCV infection from previous exposure to the virus. We studied HCV viremia
      by reverse transcription polymerase chain reaction (RT-PCR) in the 5'-noncoding
      region of the viral genome in 77 dialysis patients who were screened for anti-HCV
      by a second-generation enzyme-linked immunosorbent assay (the enzyme immunoassay
      II; Ortho HCV, 2nd generation, Ortho Diagnostic Systems Raritan, N.J.) and a
      second-generation recombinant immunoblot assay (Chiron Corporation and Ortho
      Diagnostic Systems) and prospectively evaluated for ALT elevations over a period
      of 5 years. Of 77 patients tested, 29 (38%) had active infection as shown by a
      positive PCR assay result, and of these, 26 were anti-HCV positive. Although a
      good correlation was found between circulating anti-HCV and HCV RNA in serum, 10
      (28%) of 36 anti-HCV-positive patients were HCV RNA negative by PCR, suggesting
      either low levels of viremia or past exposure to HCV and subsequent recovery. On
      the other hand, 3 (7.3%) of 41 anti-HCV-negative patients had HCV RNA in their
      sera, indicating seronegative HCV infection. The ALT level had no predictive
      value for HCV infection, because it was repeatedly normal in 18 (62%) of 29
      viremic patients. HCV genotyping was also performed and indicated that all four
      known genotypes of HCV were present in our group. In conclusion, serological
      assays are reliable for detecting exposure to HCV in hemodialysis patients;
      however, direct identification of the viral genome is required to document
      current infection.

PMID- 7505293
TI  - Analysis of discordant test results among five second-generation assays for anti
      hepatitis C virus antibodies also tested by polymerase chain reaction-RNA assay
      and other laboratory and clinical tests for hepatitis.
AB  - The diagnostic performances of five commercially available second-generation
      assays for anti-hepatitis C virus antibody, two enzyme-linked immunosorbent
      assays, one enzyme immunoassay, and two particle agglutination assays (passive
      hemagglutination assay and particle agglutination assay), were evaluated. Among
      104 samples from healthy subjects and 300 consecutive samples from patient
      ordered for routine determinations of anti-hepatitis C virus antibody in serum,
      assay results showed variable degrees of discordance for 17 samples (4.2%). These
      17 samples were further tested by an immunoblot assay, the polymerase chain
      reaction-RNA assay, and the hemagglutination inhibition assay. Four of the 17
      samples were regarded as true positive, since all supplementary assays and
      clinical data indicated active hepatitis C virus infection. Another five samples
      were considered false positive because no confirmatory evidence was obtained from
      the laboratory analysis or clinical data. The remaining eight samples were
      negative for hepatitis C virus RNA, but the results of the other supplementary
      tests were indeterminate. Some of these samples with indeterminate results may
      have been from patients with subclinical cases of disease who spontaneously
      recovered from hepatitis with persistent anti-hepatitis C virus antibody in their
      sera.

PMID- 7505294
TI  - Epidemic of Pseudomonas cepacia in an adult cystic fibrosis unit: evidence of
      person-to-person transmission.
AB  - An epidemic of Pseudomonas cepacia occurred in an adult cystic fibrosis center in
      the United Kingdom, despite a policy of segregation of infected and noninfected
      patients within the hospital. Investigation of the outbreak by ribotyping and
      pulsed-field gel electrophoresis to characterize P. cepacia strain genomes
      together with inquiry into social contacts between patients revealed evidence of
      person-to-person transmission outside the hospital environment. Segregation
      policies aimed at reducing the spread of this infection in the cystic fibrosis
      community need to encompass patient contacts outside the hospital environment.

PMID- 7505295
TI  - Glutamatergic and cholinergic projections to the pontine inhibitory area
      identified with horseradish peroxidase retrograde transport and
      immunohistochemistry.
AB  - Previous studies in our laboratory have shown that microinjection of
      acetylcholine and non-N-methyl-D-aspartate (NMDA) glutamate agonists into the
      pontine inhibitory area (PIA) induce muscle atonia. The present experiment was
      designed to identify the PIA afferents that could be responsible for these
      effects, by use of retrograde transport of wheat germ agglutinin conjugated
      horseradish peroxidase (WGA-HRP), glutamate immunohistochemistry and NADPH
      diaphorase staining techniques. Experiments were performed in both decerebrate
      and intact cats. Dense retrograde WGA-HRP labelling was found in neurons in the
      periaqueductal gray (PAG) and mesencephalic reticular formation (MRF) at the red
      nucleus (RN) level, ventral portion of paralemniscal tegmental field (vFTP),
      retrorubral nucleus (RRN), contralateral side of PIA (cPIA), pontis reticularis
      centralis caudalis (PoC), and most rostral portion of the nucleus parvicellularis
      (NPV) and nucleus praepositus hypoglossi (PH) at the level of the pontomedullary
      junction; moderate labelling was seen in pedunculopontine nucleus, pars compacta
      (PPNc), laterodorsal tegmental nucleus (LDT), superior colliculus (SC), MRF and
      PAG at the level caudal to RN, medial and superior vestibular nuclei, and
      principle sensory trigeminal nucleus (5P); and light labelling was seen in dorsal
      raphe (DR) and locus coeruleus complex (LCC). The projection neurons were
      predominantly ipsilateral to the injection site, except for both vFTP and RRN,
      which had more projection cells on the contralateral side. Double labelled WGA
      HRP/NADPH-d neurons could be found in PPNc and LDT. Double labelled WGA
      HRP/glutamatergic neurons could be seen at high densities in MRF, RRN, vFTP, and
      cPIA, moderate densities in SC, LDT, PPNc, PoC, and NPV, and low densities in PH,
      5P, DR, LCC, and PAG.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505296
TI  - Neurons synthesizing nitric oxide innervate the mammalian carotid body.
AB  - The carotid body is an arterial chemoreceptor organ sensitive to blood levels of
      O2, CO2 and pH. The present immunocytochemical and neurochemical study has
      demonstrated the presence of an extensive plexus of nitric oxide (NO)
      synthesizing nerve fibers in this organ. These nitric oxide synthase (NOS)
      containing axons are closely associated with parenchymal type I cells and with
      blood vessels in the carotid body. Denervation and retrograde tracing experiments
      have revealed that these fibers arise from NOS-immunoreactive and nicotinamide
      adenine dinucleotide phosphate (NADPH) diaphorase-positive neuronal cell bodies
      located in the petrosal ganglion and the carotid body, and dispersed along the
      glossopharyngeal and carotid sinus nerves (CSN). Within the petrosal ganglion,
      these neurons are topographically segregated from the catecholaminergic cells,
      and they contain the neuropeptide, substance P. NOS-positive autonomic
      microganglial cells in the carotid body and CSN also exhibit choline
      acetyltransferase (ChAT) immunoreactivity. Our results suggest that nitric oxide
      may be a novel neuronal messenger in the mammalian carotid body involved in the
      modulation of chemosensory transduction and transmission in this organ.

PMID- 7505297
TI  - Antibiotic resistance pattern of heat-labile enterotoxin (LT) producing
      Escherichia coli isolated from children with diarrhoea in Bangladesh: clonal
      relationships among isolates with different resistant phenotypes.
AB  - Fifty-six heat-labile, enterotoxin-producing (LT+) Escherichia coli isolated from
      33 children less than 5 years of age with diarrhoea were analysed for resistance
      to antibiotics, plasmid contents, and clonal relationships among isolates by
      ribosomal RNA (rRNA) fingerprinting (ribotyping). Fifty-five (98.2%) of the LT+
      isolates were resistant either to tetracycline alone (48.2%) or to tetracycline
      and one or more other antibiotic, i.e. ampicillin, streptomycin, chloramphenicol,
      trimethoprim-sulfamethoxazole, or nalidixic acid. Most of the isolates harboured
      one or more plasmid but antibiotic resistance patterns did not always correlate
      with particular plasmid patterns. Ribotyping of the isolates using the
      restriction endonuclease EcoRI revealed a total of 7 different ribotypes, and
      ribotypes were shared by E. coli isolates with different antibiotic resistant
      phenotypes. The results indicate that in Bangladesh at least 7 different clones
      of LT+ E. coli acquired resistance to one or more different antibiotics in
      various combinations. However, a similar drug resistance pattern was not mediated
      by the same set of plasmids in all strains. The mechanism for the emergence and
      spread of antibiotic resistance among E. coli should be investigated further in
      Bangladesh, where LT+ E. coli is an important agent of early childhood diarrhoea.

PMID- 7505298
TI  - A new approach to map transcription sites at the ultrastructural level.
AB  - We describe a new ultrastructural method for locating transcription on ultra-thin
      sections. The use of anti-DNA/RNA hybrid antibodies provides specific labeling on
      precise structures of the nuclear compartments of several cell types. All
      mammalian and plant material studied (HeLa cells, lymphocytes, onion root
      meristematic cells) showed the same pattern of labeling: fibrillar structures in
      the interchromatin region and discrete regions of the dense fibrillar component
      at the periphery of the fibrillar centers in the nucleolus. The specificity of
      the immunogold labeling was tested by RNAse H digestion and by pre-blocking the
      antibody with synthetic DNA/RNA hybrids; in both cases no gold particles were
      observed. This method has considerable advantages compared with current
      techniques, constituting a very useful tool to map transcriptionally active loci
      in a variety of cells.

PMID- 7505299
TI  - Endogenous enzymes cause structural and chemical artifacts in methacrylate- and
      celloidin-embedded sections of unfixed freeze-dried tissues.
AB  - Bovine exocrine pancreas and fish (Rivulus ocellatus marmoratus) liver containing
      pancreatic acini were cryofixed, freeze-dried, and embedded in methacrylate or
      double-embedded in celloidin and paraffin. In chemically unfixed sections
      incubated in aqueous solutions, dissolution of zymogen granules was coincident
      with loss of tissue structure and antigenicity. Type II-S soybean protease
      inhibitor at 150 mg/liter during section flotation and in aqueous reagents used
      for immunohistochemistry prevented these artifacts and allowed the use of more
      dilute antibody solutions. Loss of glycogen from fish hepatocytes was most rapid
      in areas adjacent to pancreatic acini. Rapid loss of glycogen was attributed to
      amylase and was prevented by using poly-L-lysine instead of 3
      aminopropyltriethoxysilane slide adhesive and by using alcoholic solutions during
      PAS staining. Inhibition of endogenous enzymes is an important consideration in
      the development of histological protocols with freeze-dried tissue sections.

PMID- 7505300
TI  - Localization of the G-protein G(o) in exocrine glands.
AB  - The GTP-binding protein G(o) was localized immunohistochemically in the rat
      parotid gland and in other exocrine glands with specific G(o) antibodies.
      Immunohistochemical studies revealed that affinity-purified G(o alpha) polyclonal
      antibody (GO/85) immunoreacted primarily with duct cells of the rat parotid
      gland; immunoreactivity was also noted in duct cells of the rat submandibular,
      mouse parotid, and mouse submandibular glands. Light labeling of rat parotid and
      submandibular gland acinar cells was also noted. G(o alpha) antiserum (9072)
      differing in specificity for epitopes within G(o alpha) produced similar results.
      This antiserum also immunoreacted with rat submandibular duct cell secretory
      granule membranes. In contrast, in rat and mouse pancreas G(o alpha) antibodies
      immunoreacted primarily with islet cells. Duct cells were negative but there was
      light labeling of rat pancreatic acinar cells. The apparent duct specificity of
      G(o alpha) staining was further verified by demonstrating that G(o alpha)
      antibodies immunoreacted with HSG-PA cells, a human transformed salivary duct
      cell line. Specificity in immunohistochemical labeling of HSG-PA cells was
      confirmed by Western blot analysis. The results demonstrate that G(o) appears to
      be selectively expressed in the duct cells of rat parotid gland and other
      salivary glands. The selective enrichment of G(o) in duct cells suggests that
      this G-protein plays an important role in duct cell physiology.

PMID- 7505301
TI  - A pre-embedding triple-label electron microscopic immunohistochemical method as
      applied to the study of multiple inputs to defined tegmental neurons.
AB  - For many neural regions it is of interest to know the identity of the target
      structures of two different types of inputs to that neural region. Such studies
      require use of a triple-label immunohistochemical method to differentially label
      the class of target structure and the two types of input so that they can be
      visualized at the electron microscopic (EM) level. We describe here a procedure
      for combining three different markers (diaminobenzidine, benzidine
      dihydrochloride, and silver-intensified immunogold) for triple-label EM
      immunohistochemical pre-embedding labeling. All three markers are distinct at the
      LM and EM levels. An example of this approach as applied to studying striatal
      input to the ventral tegmental area is presented and the advantages of this
      approach are discussed.

PMID- 7505302
TI  - Some serum enzymes in burns and their probable correlation with surgical shock--a
      prospective combined surgicobiochemical study.
AB  - Serum enzymes such as phosphohexoisomerase, aldolase and amylase were estimated
      in serum of 100 patients with thermal burn of different degrees. These enzymes
      were estimated at the time of admission, at 12th hour, 24th hour, 36th hour, 72nd
      hour, 7th day and 14th day. The patients with high serum levels of these enzymes
      till 72nd hour showed grave prognosis and serial measurements of these enzymes
      might help in predicting the outcome.

PMID- 7505304
TI  - [Early revascularization of the reconstructed anterior cruciate ligament using a
      patellar tendon autograft].
AB  - Early revascularization of the reconstructed anterior cruciate ligament (ACL)
      using a patellar tendon autograft was investigated microangiographically and
      electron microscopically. In sixteen skeletally mature mongrel dogs, the ACL of
      the right knee was completely excised and tunnels through the tibia and femur
      were created at the insertion sites using a 3 mm Steinmann pin. The central
      portion of the patellar tendon (3 mm wide) was pulled through the holes and
      secured with sutures and buttons. The leg was immobilized with a plaster cast at
      90 degrees of knee flexion until sacrifice. Eight dogs divided into four groups
      (two dogs each) were examined microangiographically at 1, 2, 3 and 4 weeks after
      the operation. Other eight dogs divided into four groups (two dogs each) were
      examined with an electron microscope at 3, 5, 7 and 14 days after the operation.
      The microangiographic study showed capillary buds invaded the graft from the bone
      tunnels and ran along the graft-bone interface at one week. Newly-formed
      capillaries were observed near the fat pad, but only at the surface of the graft.
      At two and three weeks, vascular sprouts anastomosed with each other, forming a
      network which extended internally into the graft. Although vascularity was
      present throughout the graft at four weeks, there was little in the midsubstance.
      The transmission electron microscopy (TEM) demonstrated that mesenchymal cells
      (undifferentiated fibroblasts) were in the process of migration to the graft in
      the area of the bone tunnels at five days. At seven days, these cells formed new
      vascular lumina and differentiated endothelial cells. At fourteen days, the newly
      formed vessels had developed basement membrane. Some of mesenchymal cells
      appeared to differentiate into fibroblast. These results suggest that bone marrow
      plays an important role in revascularization and remodelling of the reconstructed
      graft.

PMID- 7505303
TI  - [Biochemical characteristics of endothelin].

PMID- 7505305
TI  - Outpatient spinal opiate analgesia: a case report.
AB  - Outpatient spinal opiate analgesia for relief of cancer pain has been well
      described in the literature. We report a case of a patient with metastatic
      disease who received epidural morphine using a subcutaneous epidural catheter via
      home injections. The patient and his family administered the medications. There
      are several options to choose from when using epidural morphine, and each
      patient's needs must be evaluated for the appropriate system.

PMID- 7505306
TI  - Confirmation of hepatitis C virus antibody in blood donors.
AB  - Of 103,203 donations collected in Scotland and Northern Ireland over a 3-month
      period and screened for HCV antibody by Ortho or Abbott second-generation ELISAs,
      340 were found repeatedly reactive. Supplementary testing with RIBA-2 resulted in
      77 being classified as positive, 130 as indeterminate, and 133 as negative. PCR
      analysis of the positives and indeterminates indicated viraemia in 65 (84%) of
      the positives and 7 (5.5%) of the indeterminates. To determine if PCR analysis
      could be eliminated or reduced by further serological testing, all RIBA-2
      positives and indeterminates were tested by UBI and Wellcozyme ELISAs and Innolia
      and RIBA-3 immunoblots. All RIBA-2 positives with bands to more than 1 gene
      product were detected in all 4 systems, but > 60% of RIBA-2 indeterminates were
      negative in those tests that contain either recombinant antigens or synthetic
      peptides derived independently from those used by Ortho/Abbott tests. A
      comparison of data from the 79 reactive with the core (c22) region revealed only
      16 samples reactive in all 4 systems as well as Ortho and Abbott. These 16
      included all 6 of the PCR positives in the 79 c22 indeterminate samples. ELISAs
      and immunoblots using independently derived antigens can offer a useful method of
      screening out nonspecific reactions in Ortho or Abbott ELISAs, hence reducing the
      need for PCR testing. Some caution is required as all such tests do not contain
      identical mixes of antigenic material.

PMID- 7505308
TI  - Low prevalence of hepatitis C virus antibodies in chronic liver disease in
      northwest China.
AB  - To evaluate the prevalence of hepatitis C virus infection in northwest China, 179
      chronic liver disease patients in this area were examined for antibody to
      hepatitis C virus core protein (anti-HCVcore). This antibody was found in only 5
      (14 percent) of 37 chronic non-A, non-B liver disease patients, in 11 (16%) of 67
      asymptomatic hepatitis B virus carriers, and in 20 (27%) of 75 chronic hepatitis
      B patients. High titers of anti-HCVcore (cut off index > 2) were observed in 3
      (60%), 5 (45%), and 9 (45%) of the anti-HCVcore-positive cases of these groups,
      respectively. We further investigated the seroprevalence of antibodies to
      hepatitis B virus in the 37 chronic non-A, non-B liver disease patients. All 5
      anti-HCVcore-positive cases were positive for a hepatitis B virus marker, with
      only 44% (14/32) of the anti-HCVcore-negative patients (P < 0.05). Based on these
      findings, it is concluded that the prevalence of hepatitis C virus infection in
      chronic non-A, non-B liver disease is unexpectedly low in northwest China and
      that hepatitis B and C viruses seem to have a similar mode of infection in that
      area.

PMID- 7505307
TI  - Characterization of minor and major antigenic regions within the hepatitis B
      virus nucleocapsid.
AB  - Hepatitis B core antibodies (anti-HBc) appear very early during the course of the
      hepatitis B virus infection and often persist years after viral clearance. In
      order to characterize the immunodominant domain of the HBcAg, the human immune
      response against the HBV nucleocapsid (HBcAg) was analyzed by using 14 synthetic
      peptides. Anti-HBc antibodies were detected by an indirect enzyme-linked
      immunosorbent assay (ELISA) with HBc peptides. Results suggest that the anti-HBc
      response is heterogeneous and directed against the whole primary structure of the
      HBc protein. Results also indicate that the epitopes recognized by anti-HBc
      antibodies can vary with the stages of the disease. In most sera from patients
      with serological evidence of acute HBV infection, anti-HBc antibodies recognized
      all the HBc peptides; conversely, after the acute phase, anti-HBc antibodies
      recognized predominantly epitopes located within the central region of the HBc
      protein from residue 74 to 123. Our results suggest that the HBV core protein is
      made up of two antigenic regions: a major one expressing a family of
      immunodominant epitopes from residue 74 to 123, whereas the minor encompasses the
      rest of the protein. The concept of the conformational nature of the unique HBcAg
      determinant is discussed, suggesting numerous families of linear epitopes.

PMID- 7505309
TI  - Prevalence of hepatitis C virus in family members of patients with hepatitis C.
AB  - To investigate the prevalence of hepatitis C virus in the family members of
      patients with hepatitis C, we examined antibody to hepatitis C virus with a
      second-generation enzyme-linked immunosorbent assay and viral RNA with a combined
      assay of reverse transcription and polymerase chain reaction in sera. Among 219
      (75 spouses, 110 children, and 34 others), 26 (12%) were antibody positive. The
      positive rate of antibody to hepatitis C virus was significantly higher than that
      of the control group (2.0%) and of volunteer blood donors in our district (1.5%),
      and it increased with age. In particular, the positive rate of antibody to
      hepatitis C virus among spouses was high (24%). Among family members with
      elevated ALT, 59% were antibody positive, which was significantly higher than
      that of the control group (11%). Of the 26 who were antibody positive, 21 (81%)
      had viral RNA, whereas of the 70 who were antibody negative, only one (1.4%) had
      viral RNA. These data suggest that hepatitis C virus was transmitted by the
      infrafamilial route during long duration of contact with patients or sexual
      transmission. In family members, hepatitis C viral infection is the main cause of
      liver disorder, and many who were antibody-positive with a second-generation
      enzyme-linked immunosorbent assay had viremia in the sera.

PMID- 7505310
TI  - Alternative splicing of a 51-nucleotide exon that encodes a putative protein
      kinase C phosphorylation site generates two forms of the chicken gamma
      aminobutyric acidA receptor beta 2 subunit.
AB  - Complementary DNAs that encode two forms of the chicken gamma-aminobutyric acid
      type A (GABAA) receptor beta 2 subunit have been isolated. These polypeptides
      differ by the presence of (beta 2L) or absence (beta 2S) of 17 amino acids, which
      contain a possible target for phosphorylation by protein kinase C, in the large
      intracellular loop between the third and fourth membrane-spanning domains. The
      extra sequence in the chicken beta 2L subunit is not found in previously
      published GABAA receptor beta 2-subunit sequences. Analysis of genomic DNA has
      revealed that the two beta 2-subunit mRNAs arise by alternative splicing of a
      novel 51-nucleotide exon. Although the two beta 2-subunit transcripts appear to
      be present in 1-day-old chick brain at similar steady-state levels, we have been
      unable to detect an mRNA for the long form of the beta 2 subunit in either the
      bovine or the rat. Because the various GABAA receptor genes are thought to have
      arisen by duplication of a common ancestor, our data, taken together with that on
      the gamma 2 subunit, which occurs in two forms that arise by alternative splicing
      of a 24-nucleotide exons, suggest that the coding region of the primordial gene
      or one of its very early descendants contained 10 exons, not nine as previously
      thought.

PMID- 7505312
TI  - Differences in the distribution of cytochrome b561 and synaptophysin in dog
      splenic nerve: a biochemical and immunocytochemical study.
AB  - Compared with neurons of the CNS, the organization of the peripheral adrenergic
      axon and nerve terminal is more complex because two types of neurotransmitter
      containing vesicles, i.e., large (LDVs) and small dense-core vesicles, coexist
      with the axonal reticulum (AR) and the well-characterized small synaptic
      vesicles. The AR, which is still poorly examined, is assumed to play some role in
      neurosecretion. We have studied the subcellular localization of noradrenaline,
      cytochrome b561, and synaptophysin in control and ligated dog splenic nerve using
      both biochemical and ultrastructural approaches. Noradrenaline and cytochrome
      b561 coaccumulated proximal to a ligation, whereas distally only the latter was
      found. Despite a codistribution with noradrenaline at high densities in sucrose
      gradients, synaptophysin did not accumulate on either side of the ligation. At
      the ultrastructural level, cytochrome b561 immunoreactivity was found on LDVs and
      AR elements, both accumulating proximal to the ligation. Distally, the
      multivesicular bodies (MVBs), immunolabeled for cytochrome b561, account for the
      retrograde transport of LDVs and AR membranes retrieved at the nerve terminal. No
      synaptophysin immunoreactivity could be detected on LDVs, AR, or MVBs. The
      results obtained from the ligation experiments together with the ultrastructural
      data clearly illustrate that synaptophysin is absent from LDVs and AR elements in
      adrenergic axons.

PMID- 7505311
TI  - Selective lesions by manganese and extensive damage by iron after injection into
      rat striatum or hippocampus.
AB  - Regional 45Ca2+ accumulation and analysis of monoamines and metabolites in
      dissected tissues were used to localize, quantify, and characterize brain damage
      after intracerebral injections of Mn2+ into striatum and hippocampus. The
      specificity of Mn(2+)-induced lesions is described in relation to brain damage
      produced by local Fe2+ or 6-hydroxydopamine (6-OHDA) injections. In striatum,
      Fe2+ and Mn2+ produced dose-dependent (0.05-0.8 mumol) dopamine (DA) depletion,
      with Fe2+ being 3.4 times more potent than Mn2+. Studies examining the time
      course of changes in monoamine levels in striatum following local application of
      0.4 mumol of Mn2+ revealed maximal depletion of all substances investigated
      (except 5-hydroxyindoleacetic acid) after 3 days. The effects on DA (87%
      depletion at day 3) and its major metabolites were most pronounced and lasted
      until at least 90 days (40% depletion), whereas serotonin and noradrenaline
      levels recovered within 21 and 42 days, respectively. In addition, levels of 3
      methoxytyramine, which is used as an index of DA release, also recovered within
      42 days, indicating a functional restoration of DA neurotransmission despite
      substantial loss of DA content. Intrastriatal Mn2+ (0.4 mumol) produced time
      dependent 45Ca2+ accumulation in striatum, globus pallidus, entopeduncular
      nucleus, several thalamic nuclei, and substantia nigra pars reticulata
      ipsilateral to the injection site. In contrast, 6-OHDA injected at a dose
      equipotent in depleting DA produced significantly less 45Ca2+ accumulation in
      striatum and globus pallidus and no labeling of other brain areas, whereas Fe2+
      (0.4 mumol) produced extensive 45Ca2+ accumulation throughout basal ganglia,
      accumbens, and cerebral cortex. In hippocampus, high Mn2+ (0.4 mumol) produced
      limited 45Ca2+ accumulation in subiculum and dentate gyrus, whereas low Fe2+ (0.1
      mumol) produced widespread 45Ca2+ accumulation throughout hippocampus, thalamus,
      and cerebral cortex. It is concluded that (a) Mn2+ is selectively neurotoxic to
      pathways intrinsic to the basal ganglia, (b) intrastriatal injections can be used
      as a model for systemic Mn2+ intoxications, and (c) high endogenous Fe3+ and/or
      catecholamine levels potentiate the neurotoxicity of Mn2+.

PMID- 7505313
TI  - Postmortem stability of monoamines, their metabolites, and receptor binding in
      rat brain regions.
AB  - The effects of postmortem delay, time of storage, and freezing, thawing, and
      refreezing tissue samples were studied in postmortem rat brain using conditions
      that reflect the handling of postmortem human brain before neurochemical
      analysis. The levels of monoamines and metabolites in the striatum and cingulate
      and occipital cortex were measured using alumina extraction and HPLC methods.
      Binding of raclopride to dopamine D2, SCH-23390 to dopamine D1, ketanserin to
      serotonin 5-HT2, 8-hydroxy-2-(di-n-propylamino)tetralin to serotonin 5-HT1A, and
      cholecystokinin (CCK)-8 to CCK-B sites was measured in tissue homogenates from
      the striatum or fronto-parietal cortex. An 18-h postmortem delay before
      dissection and storage resulted in region-specific changes in monoamine and
      metabolite levels. Binding to striatal D1 and frontoparietal cortex CCK-B sites
      was reduced over the course of a 27-h postmortem delay. Binding to D2 and 5-HT
      sites was relatively stable. Storage of tissue for up to 8 months also resulted
      in region-specific changes in monoamine and metabolite levels. No changes in
      receptor binding were seen after long-term storage. Freezing, thawing, and
      refreezing tissue samples resulted in increased levels of striatal 3,4
      dihydroxyphenylacetic acid and decreased binding to striatal D2 sites. These
      results demonstrate time-, temperature-, and storage-dependent regional
      differences in the stability of monoamines and their metabolites and in binding
      to various receptor sites. These differences in stability and binding should be
      accounted for to interpret accurately the effects of neurological disorders on
      neurotransmitter dynamics in postmortem human brain tissue.

PMID- 7505314
TI  - Induction of nitric oxide synthase in rat C6 glioma cells.
AB  - We have examined the induction of nitric oxide synthase (NOS) activity in the rat
      astrocyte-derived C6 glioma cell line. In contrast to the previous results with
      primary astrocyte cultures, incubation of C6 cells with bacterial endotoxin
      lipopolysaccharide (LPS; 1 microgram/ml for 24 h) did not stimulate NO2
      production. However, addition of either tumor necrosis factor-alpha (TNF-alpha)
      or interferon-gamma (IFN-gamma), cytokines that by themselves had no effect on
      NOS activity, imparted LPS responsiveness onto these cells in a dose-dependent
      manner (EC50 values of 39 ng/ml of TNF-alpha and 9.4 U/ml of IFN-gamma), and the
      effect of TNF-alpha could be further potentiated (twofold) by the presence of
      interleukin-1 beta. The simultaneous presence of TNF-alpha and IFN-gamma yielded
      a greater response than either cytokine alone; however, the respective EC50
      values were not affected. A cytoplasmic extract from induced C6 cells catalyzed
      the Ca(2+)-independent conversion of L-arginine to L-citrulline, with an apparent
      Km of 51.2 microM, and this activity could be blocked by L-arginine analogues in
      the potency order amino > methyl > nitroarginine. Immunoblot analysis revealed an
      apparent molecular mass of 125 kDa for the NOS protein induced in C6 cells. These
      results indicate that the combination of LPS plus cytokines can induce NOS
      activity in C6 glioma cells with properties similar to those of the enzyme
      expressed in primary astrocyte cultures.

PMID- 7505315
TI  - Attenuation of methamphetamine-induced neurotoxicity in copper/zinc superoxide
      dismutase transgenic mice.
AB  - Administration of methamphetamine (METH) to rats and nonhuman primates causes
      loss of terminals in the nigrostriatal dopaminergic system. The mechanism by
      which METH causes its neurotoxicity is not known. To evaluate further the role of
      oxyradicals in METH-induced neurotoxicity, we have tested its effects in CuZn
      superoxide dismutase (SOD) transgenic (Tg) mice, which express the human CuZnSOD
      gene. In non-Tg mice, acute METH administration causes significant decreases in
      levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striata
      and cortices of non-Tg mice. In contrast, there were no significant decreases in
      cortical or striatal DA in the SOD-Tg mice. The effects of METH on DOPAC were
      also attenuated in both structures of these SOD-Tg mice. Chronic METH
      administration caused decreases in levels of striatal DA and DOPAC in the non-Tg
      mice, whereas the SOD-Tg mice were not affected. These results suggest that METH
      induced dopaminergic toxicity in mice may be secondary to increased production of
      reactive oxygen species such as the superoxide radical.

PMID- 7505316
TI  - Nerve growth factor increases the transcriptional activity of the rat neuronal
      nicotinic acetylcholine receptor beta 4 subunit promoter in transfected PC12
      cells.
AB  - Neuronal nicotine acetylcholine receptors play a key role in synaptic
      transmission in the nervous system. Although complementary DNA clones encoding a
      family of acetylcholine receptor subunits have been isolated and subsequent
      anatomical studies indicate differences in the temporal and spatially restricted
      patterns of expression of each gene, the cellular and molecular mechanisms
      controlling the expression of these genes are unknown. As part of a long-term
      goal to elucidate these mechanisms, we have been identifying and characterizing
      regions of the receptor subunit genes involved in transcriptional regulation.
      Here, we report the localization of the transcription initiation site of the rat
      beta 4 subunit gene, demonstrate using transient transfection analysis of PC12
      cells that sequences upstream of this site are capable of activating
      transcription of a heterologous gene, and show that this transcriptional activity
      is enhanced in PC12 cells by treatment with nerve growth factor.

PMID- 7505317
TI  - The role of P-type calcium channels in the depolarization-induced activation of
      nitric oxide synthase in frontal cortex.
AB  - In this study we demonstrate that 50 mM K+ stimulates the conversion of L
      [3H]arginine to L-[3H]citrulline and that this effect is blocked by 10 microM N
      omega-nitro-L-arginine, a nitric oxide synthase inhibitor, and Ca(2+)-free
      conditions. Amiloride (1 mM) and low Na+ conditions were used to test the
      possible involvement of the Na(+)-Ca2+ exchanger. These treatments were without
      effect. The calcium channel blockers 10 mM Mg2+, 100 microM Cd2+, and 10 mM Co2+
      also blocked the K+ response, suggesting the involvement of voltage-dependent
      calcium channels (VDCCs). The specific VDCC involved seems to be the P type, as
      funnel-web spider toxin blocked the response whereas 200 microM Ni2+, 10 microM
      nifedipine, and 100 nM omega-conotoxin did not.

PMID- 7505318
TI  - Soybean trypsin inhibitor(s) reduce absorption of exogenous and increase loss of
      endogenous protein in miniature pigs.
AB  - It was the purpose of this study to define whether trypsin inhibitors impair
      protein digestibility via enhanced loss of exogenous or endogenous protein by
      quantifying those losses using the homoarginine technique, recently developed in
      this laboratory. Pigs fitted with permanent ileal T-cannulas were fed test meals
      containing homoarginine-labeled protein. The meals contained casein and
      increasing doses of trypsin inhibitors (Experiment 1) or alternatively either
      heat-treated or raw ground soybeans (Experiment 2). Following a casein meal (425
      mmol nitrogen, no trypsin inhibitors), ileal protein was predominantly of
      endogenous rather than of exogenous origin (105 vs. 9 mmol nitrogen). Addition of
      isolated trypsin inhibitors (3000 mg) enhanced appearance of both endogenous and
      exogenous protein at the ileum (by 73 and 9 mmol nitrogen, respectively). Feeding
      raw instead of heat-treated soybeans in one single test meal caused a significant
      increase of endogenous protein from 217 +/- 42 to 263 +/- 47 mmol (mean +/- SEM)
      and of exogenous protein from 16 +/- 3 to 48 +/- 14 mmol. If fed continuously for
      1 wk, a raw soybean diet caused endogenous protein loss to rise significantly
      from 221 +/- 26 to 432 +/- 85 mmol. We conclude that ingestion of food containing
      trypsin inhibitor affects nitrogen balance more by losses of amino acids of
      endogenous secreta than by losses of dietary amino acids.

PMID- 7505319
TI  - Pancreatic enlargement is evident in rats fed diets containing raw soybeans
      (Glycine max) or cowpeas (Vigna unguiculata) for 800 days but not in those fed
      diets based on kidney beans (Phaseolus vulgaris) or lupinseed (Lupinus
      angustifolius).
AB  - Pancreatic weights and composition were studied with rats fed diets containing
      raw legume seeds for up to 800 d. Rapid pancreatic enlargement was induced by
      dietary soybeans (Glycine max) (high Kunitz and Bowman-Birk trypsin inhibitor
      contents, moderate lectin content) during the initial 150 d. Over the next 200 d
      the rate of pancreatic growth was similar to that in controls. After 350 d a
      second period of rapid pancreatic growth occurred. Macroscopic pancreatic nodules
      were evident in a number of rats fed soybeans for 500 d or more. A similar
      pattern of pancreatic growth was observed in rats fed dietary cowpeas (Vigna
      unguiculata) (high Bowman-Birk inhibitor content, low lectin content). Extensive
      pancreatic growth was also found in young rats fed moderate dietary levels of
      kidney beans (Phaseolus vulgaris) (low Bowman-Birk inhibitor content, high lectin
      content). However, the trophic effects diminished with time, and from 100 d
      onwards, little enlargement was evident. Consumption of a lupinseed (Lupinus
      angustifolius) diet (low trypsin inhibitor, low lectin content) did not cause
      pancreatic enlargement. The initial pancreatic growth induced by dietary soybeans
      seemed to be due to the lectins and trypsin inhibitors, whereas the second period
      of pancreatic growth was possibly due primarily to the trypsin inhibitors.

PMID- 7505320
TI  - Distribution of anionic sites during increasing tight junctional permeability in
      the rat submandibular gland.
AB  - We sought to determine the effect of substance P salivary stimulation on both
      electrical charges and cellular permeability in the tight junctions of rat
      submandibular gland cells. Microperoxidase (1,900 daltons) was used as a tracer.
      It was administered by close-arterial infusion via the glandular arteries, and
      secretory routes of acinar cells in the gland were determined cytochemically. In
      the resting gland, microperoxidase reaction product filled the lateral
      intercellular spaces up to the tight junctions, but did not penetrate them. In
      the substance P-stimulated gland, microperoxidase reaction product was present
      within tight junctions and the lumen. Both distribution and mobility of anionic
      sites on the surface of the submandibular gland cells were studied utilizing
      multivalent ligand, ruthenium red and cationized ferritin as probes. In the
      resting gland, ruthenium red deposits were located uniformly in all areas of the
      basal membrane and intercellular spaces except for the tight junctional region of
      acinar and ductal cells. In substance P-stimulated gland, ruthenium red deposits
      were present in the tight junctional region and, to a lesser extent, in the
      intercellular spaces. Electrical charges of the tight junctions area of the
      lateral plasma membrane were studied using intraductal injection of cationized
      ferritin. In the resting gland, cationized ferritin probe was present in the
      intercellular spaces and was bound weakly in the tight junctional region. In the
      substance P-stimulated gland, cationized ferritin was firmly adherent to the
      tight junctional region.

PMID- 7505322
TI  - Immunopathogenesis of chronic inflammatory periodontal disease: cellular and
      molecular mechanisms.
AB  - Recent studies of the cellular mechanisms involved in chronic inflammatory
      periodontal disease (CIPD) have contributed significantly to our understanding of
      the pathogenesis of the disease process. Functional studies have demonstrated
      polymorphonuclear neutrophil (PMN) chemotactic defects in some 70% of subjects
      with localized juvenile periodontitis while chemiluminescence data have suggested
      that peripheral blood PMNs from young subjects with adult periodontitis (AP) may
      be in a metabolically active state. Further studies have shown that stimulation
      of PMNs with a number of periodontopathic bacteria resulted in the production of
      an IL-1 inhibitor suggesting a possible regulatory role for PMNs in CIPD in
      addition to their established protective role. Most work on the immunoregulation
      of CIPD has, however, concentrated on T-cells. Recent limit dilution analysis has
      demonstrated the presence of periodontopathic bacteria-specific T cells in
      peripheral blood and the involvement and homing of these cells to the local
      lesions of CIPD is currently the focus of many studies. In animal studies,
      Actinobacillus actinomycetemcomitans (Aa)-specific T-cell clones home to the
      gingival tissues where they may exert a protective role. Homing and retention of
      lymphocytes to and in specific sites is dependent upon the expression of adhesion
      molecules. Recent data indicate however, that while there are increasing levels
      of ICAM-1, LECAM-1 and PECAM-1 expression with increasing degrees of
      inflammation, there are no differences between gingivitis and periodontitis
      lesions. Cytokine profiles may be related to the role of T-cell clones homing to
      the gingiva in CIPD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505323
TI  - Heterogeneity and selective localisation of T cell clones in human skin and
      gingival mucosa.

PMID- 7505324
TI  - Skin wound healing: some biochemical parameters in guinea-pig.
AB  - Hairs were removed from the dorsal skin of guinea-pigs and 5-6 wounds (7 x 7 mm)
      were surgically induced by totally removing the epidermal and part of the dermal
      surface. They were then allowed to heal. The newly formed wound tissues were
      dissected at different times during the process and analysed by biochemical and
      histological methods. Hydroxyproline, proteins, DNA and semicarbazide-sensitive
      amine oxidase (SSAO) were measured, as were [14C]leucine and [3H]thymidine
      incorporation in some samples. The peroxidase-like activity of plasma albumin and
      the histology of wounds stained with haematoxylin-eosin were also studied. It was
      shown that SSAO enzymes, which are present in normal guinea-pig skin and have a
      high affinity for benzylamine are localized in fibroblasts. During skin healing
      in the newly formed tissue there was an increase in protein content which reached
      a maximum after 4-6 days; DNA content also increased. The rate of incorporation
      of [3H]thymidine and [14C]leucine paralleled DNA and protein content,
      respectively. The content of hydroxyproline had greatly decreased with respect to
      that in normal skin after 2-10 days. SSAO activity increased much less than DNA
      after 4 days whereas after 10-11 days it increased more than DNA, thus indicating
      that at this time it was probably produced by fibroblasts. No significant
      increase in the peroxidase-like activity of albumin was observed 4, 8 or 11 days
      after surgery. Treatment of the animals with methylprednisolone acetate (20 mg kg
      1, i.m.) two days before surgery decreased the rate of skin healing but did not
      alter the level of albumin peroxidase activity of the plasma.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7505321
TI  - The combination of antiangiogenic agents to inhibit primary tumor growth and
      metastasis.
AB  - Neovascularization is a critical component for the growth of tumors and is a
      dominant feature in diseases such as diabetic retinopathy and hemangiomas in
      infancy. Angiogenesis inhibition is a potentially important therapeutic modality.
      We have previously reported that AGM-1470 is a fungal-derived angiogenesis
      inhibitor that suppresses primary tumor growth and metastases and is also
      nontoxic. alpha-Interferon, an angiogenesis inhibitor, is effective in the
      treatment of life-threatening hemangiomas. We therefore attempted to treat murine
      primary tumors and metastases with a combination of AGM-1470 and alpha/beta
      interferon. Treatment began after solid tumors formed. Six-week-old syngeneic
      C57BI/6 mice were treated for 21 days with either AGM-1470, or alpha/beta
      interferon or AGM-1470 + alpha/beta-interferon. The combination of the
      angiogenesis inhibitors AGM-1470 and alpha/beta-interferon suppressed tumor
      growth by 80% compared with controls (P < or = .001). AGM-1470 and alpha/beta
      interferon inhibited pulmonary metastatic tumor growth greater than sevenfold (P
      < or = .001) compared with controls. These effects were better than either
      inhibitor alone, and the combined effect was additive. Combination of
      angiogenesis inhibitors may be useful in the treatment of tumors and other
      angiogenesis-dependent diseases.

PMID- 7505325
TI  - Inhibition of nitric oxide synthase by a superoxide generating system.
AB  - Although superoxide anion is known to inactivate nitric oxide (NO) once formed,
      its effect on NO synthesis is unclear. In this study, xanthine oxidase
      hypoxanthine, a superoxide anion generating system, inhibited bovine cerebellum
      NO synthase activity as measured by the conversion of L-[3H]arginine to L
      [3H]citrulline. This inhibition by xanthine oxidase was concentration-dependent.
      Superoxide dismutase-catalase and allopurinol, an inhibitor of xanthine oxidase,
      attenuated in part the inhibition of NO synthase activity by xanthine oxidase.
      Xanthine oxidase also produced a decrease in the partial pressure of oxygen in
      the assay mixture. The inhibition of NO synthase activity by xanthine oxidase was
      reversed completely when oxygen was passed continuously through the reaction
      mixture. This study suggests that a decrease in oxygen concentration caused by
      superoxide generation may inhibit NO synthesis.

PMID- 7505326
TI  - Inhibition of endothelial nitric oxide synthase by ebselen. Prevention by thiols
      suggests the inactivation by ebselen of a critical thiol essential for the
      catalytic activity of nitric oxide synthase.
AB  - NO synthase (NOS) is a unique P-450-type enzyme containing both a reductase and a
      heme domain on a single polypeptide. We show that ebselen [Ebs, 2-phenyl-1,2
      benzisoselenazol-3-(2H) one], a nontoxic selenoorganic compound known to break a
      cysteine thiolate/Fe bond of some of P-450 enzymes, is a relatively selective
      inhibitor of endothelial isoform of NOS. In rings of rabbit aorta, Ebs
      irreversibly blocked both the basal as well as acetylcholine- or calcium
      ionophore A23187-stimulated release of nitric oxide with an IC50 of 6 microM. In
      homogenates of bovine aortic endothelial cells, Ebs inhibited the activity of
      NOS, assayed by monitoring conversion of L-[2,3-3H]arginine to L-[2,3
      3H]citrulline, with an IC50 of 8.5 microM. The inhibitory action of Ebs was
      prevented by glutathione, N-acetyl-L-cysteine or dithiothreitol (30-500 microM).
      The prevention by thiols of Ebs-induced inhibition of NOS suggests that these are
      competing with a thiol group of NOS that is essential for the catalytic activity
      of the enzyme. The consequence of the presence of thiols is the "trapping" of Ebs
      in the form of inactive selenyl sulfides. Consistent with the proposed mechanism
      of action of Ebs is lack of activity of diselenide of Ebs, which also
      demonstrates that the action of Ebs is independent of its glutathione peroxidase
      like activity. In comparison to endothelial preparations, IC50 values of Ebs for
      inhibition of soluble isoforms of NOS present in homogenates of porcine
      cerebellum and of spleens obtained from lipopolysaccharide-treated rats were more
      than 30-fold higher.

PMID- 7505327
TI  - Ionophoretic-like properties of ketorolac for calcium.
AB  - Ketorolac is an analgesic drug known to induce its therapeutic effect by
      inhibiting prostaglandin synthesis. In this work we introduce the nonsteroidal
      antialgesic drug as a compound with ionophoretic properties for calcium ions,
      showing that ketorolac induces mitochondrial Ca++ release. This reaction did not
      depend on an uncoupler-like action, because the drug does not collapse the
      internal negative membrane potential nor does it affect oxidative
      phosphorylation. In addition, it is shown that ketorolac ferries calcium ions
      into energized liposomes and has a hydrophobic phase with an affinity constant of
      4 x 10(-3). The therapeutic action of ketorolac is related to its ionophoretic
      properties in addition to its well known inhibitory effect on the cyclooxygenase
      enzyme.

PMID- 7505328
TI  - Pharmacological characterization of the pressor response to tachykinins in
      isolated perfused rat kidney.
AB  - The pharmacological effects of substance P (SP), neurokinin A (NKA), an amino
      terminal fragment of SP and related tachykinin receptor agonists on renal
      resistance vessels were assessed in isolated rat kidney perfused at constant rate
      (3 ml min-1 g-1 of tissue) with a modified Krebs-Ringer bicarbonate buffer. At a
      basal perfusion pressure (PP) of 75 +/- 6 mm Hg (n = 5), bolus injections of SP
      (1-33.3 nmol) had no significant vasoactive effect. After a sustained increase in
      base-line PP (134 +/- 10 mm Hg) produced by 1 microM phenylephrine, SP evoked a
      dose-dependent increase in PP. The largest dose of SP increased PP by 60 +/- 5 mm
      Hg. Physalaemin and kassinin had similar effects as SP but caused a smaller
      increase in PP at the largest dose. NKA was less potent than the other
      tachykinins. The vasoconstrictor response to SP was not blocked by 1 microM
      phentolamine when angiotensin II (0.22-0.26 microM) was used to increase basal
      tone (n = 5). Thus, the response to SP is not mediated by norepinephrine. The N
      terminal SP fragment, SP(1-7), had no effect on PP, which suggested that the
      pressor response to SP is C-terminal dependent and tachykinin receptor mediated.
      The selective NK-1 receptor agonist, [Sar9,Met(O2)11]SP, had no significant
      effect on PP. By contrast, the selective NK-2 and NK-3 receptor agonists, GR64349
      and [MePhe7]NKB, produced concentration-dependent pressor responses and were more
      potent than SP (116 +/- 8 and 134 +/- 15 mm Hg increases in PP at 33.3 nmol,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505329
TI  - Functional role of charybdotoxin-sensitive K+ channels in the resting state of
      cerebral, coronary and mesenteric arteries of the dog.
AB  - To determine the possible role of Ca(++)-activated K+ (KCa) channels in the
      regulation of resting tone of arteries, the effects of agents that interact with
      these channels on tension and 86Rb efflux were examined in endothelium-denuded
      strips of cerebral (middle cerebral, posterior cerebral and basilar), coronary
      and mesenteric arteries of the dog. Strips of cerebral arteries maintained a
      myogenic tone; i.e., the resting tone decreased when either the Krebs' solution
      was replaced with a Ca(++)-free solution or nifedipine was added. The addition of
      charybdotoxin, a blocker of large conductance KCa channels, to the resting strips
      (strips at a resting state) caused a concentration-dependent contraction in the
      cerebral arteries but not in the coronary or mesenteric artery. In resting strips
      preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly
      greater in the cerebral arteries than in the coronary and mesenteric arteries.
      The addition of nifedipine to the resting strips decreased the basal 86Rb efflux
      rate constant in the cerebral and coronary arteries. Effects of nifedipine on
      tension and 86Rb efflux in 20.9 mM K(+)-contracted strips of the mesenteric
      artery were comparable to the effects of this blocker in the resting strips of
      the middle cerebral artery. The 86Rb efflux rate constant during the stimulation
      with 65.9 mM K+ was similar for the middle cerebral and mesenteric arteries.
      Studies using 1- or 5-min pulse labeling with 45Ca demonstrated increased basal
      45Ca influx in the resting state of cerebral arteries compared with the coronary
      and mesenteric arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505330
TI  - Role of calcium-activated K+ channels in vasodilation induced by nitroglycerine,
      acetylcholine and nitric oxide.
AB  - A comparative analysis was carried out of the sensitivities of in vitro
      vasorelaxations by nitroglycerine (NTG), acetylcholine (ACh) and nitric oxide
      (NO) to blockade by glyburide, a blocker of ATP-sensitive K+ channels (KATP), as
      well as to blockade by charybdotoxin (ChTX) and iberiotoxin (lbTX), potent
      blockers of calcium-activated K+ channels (KCa). In the isolated rabbit
      mesenteric artery (RMA) precontracted with 5 microM norepinephrine (NE), ACh
      (0.01-1 microM), NTG (0.01-5 microM) and NO (0.075-2.7 microM) produced a dose
      dependent vasodilation. Glyburide (0.5 microM) had no significant effect on
      relaxation dose-response curves (DRCs) to ACh, NTG or NO. In contrast, glyburide
      completely abolished the relaxation DRC by pinacidil, a known KATP opener. ChTX
      (10 or 100 nM) caused an inhibition of relaxation DRCs to ACh, NTG and NO. In all
      cases, ChTX shifted the relaxation DRC to the right and depressed the maximal
      response. Another potent KCa blocker, lbTX (20 nM) also significantly inhibited
      relaxation DRCs to NTG, ACh and NO and inhibited maximal relaxation response to
      SNP. The effects of ChTX and lbTX were selective; they did not inhibit
      relaxations by pinacidil and forskolin. Finally, it was observed that the use of
      80 mM K+ as a contractile stimulus inhibited NTG relaxations in a manner similar
      to the KCa blockers. Collectively, these data provide strong support for the
      hypothesis that the activation of KCa plays an important role in mediating the
      vasorelaxation caused by NTG, SNP, ACh and NO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505331
TI  - Nitric oxide synthase inhibitor inhibits catecholamines release caused by
      hypogastric sympathetic nerve stimulation.
AB  - Recent studies suggest that nitric oxide (NO) plays a significant role in the
      parasympathetic inhibitory neurotransmission to the internal and sphincter (IAS).
      The role of NO in the sympathetic neurotransmission in the gut is not known. The
      resting intraluminal pressures of anesthetized opossum IAS (IASP) were monitored
      using low-compliance continuously perfused catheters. The plasma levels of
      catecholamines norepinephrine, epinephrine and dopamine were measured using a
      radioenzymatic assay. Parallel studies to determine the effects of hypogastric
      nerve stimulation (HGNS) on the resting IASP and catecholamine release were
      performed. The influence of NO in the sympathetic neurotransmission was
      determined by examining the effect of the NO synthase inhibitor L-NG-nitro
      arginine (L-NNA) and the reversal of the effect by L-arginine. HGNS caused a
      frequency-dependent rise in the IASP accompanied by rises in norepinephrine,
      epinephrine and dopamine levels. The increases in the IASP and norepinephrine,
      epinephrine and dopamine levels were stereoselectively and significantly
      attenuated by L-NNA. Furthermore, the L-NNA-induced attenuation of rises in the
      resting IASP and catecholamine levels in response to HGNS was reversed
      stereoselectively by L-arginine. These studies for the first time (to the
      authors' knowledge) show that the NO synthase inhibitor causes specific
      suppression of sympathetic neurotransmitter release in the gut smooth muscle. It
      was concluded that, in the anorectum, NO has a facilitory role in the release of
      sympathetic neurotransmitters.

PMID- 7505333
TI  - Angiotensin-converting enzyme inhibition during development alters calcium
      regulation in adult hypertensive rats.
AB  - Studies have shown that angiotensin-converting enzyme (ACE) inhibitor treatment
      in young genetically hypertensive rats prevents the full expression of blood
      pressure and vascular abnormalities in the adult. This model provides unique
      conditions with which to study the pathogenesis of altered Ca++ regulation.
      Normotensive (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP)
      received at 6 to 10 weeks of age either ACE inhibitor (ramipril),
      hydralazine/hydrochlorothiazide or no treatment. At 17 weeks of age, rats were
      anesthetized, and vascular tissue was excised. Thoracic aorta challenged with 20
      mM caffeine in Ca(++)-free buffer produced a phasic contractile response. The
      magnitude of this phasic response was used as a measure of Ca++ released from
      intracellular stores; a direct correlation between this phasic response and
      systolic blood pressure was observed. A concentration-response curve to Bay K8644
      was performed on carotid arteries; a direct correlation of force development to
      Bay K8644 and systolic blood pressure was observed. All WKY groups showed lower
      blood pressure and force development in response to Bay K8644 than did SHRSP.
      Treatment with ramipril reduced blood pressure and force development in response
      to Bay K8644 in adult SHRSP, although not to levels of WKY rats, whereas WKY rats
      were unaffected by treatment. These data support the hypothesis that contractile
      responses to Bay K8644 in carotid arteries and caffeine in aorta parallel changes
      in systolic blood pressure. We conclude that alteration of Ca++ regulation in
      hypertension is directly related to elevated blood pressure and mediated by an
      angiotensin II-sensitive mechanism during development.

PMID- 7505332
TI  - Nimesulide, a sulfonanilide nonsteroidal anti-inflammatory drug, inhibits
      mediator release from human basophils and mast cells.
AB  - Nimesulide (NIM) is a sulfonanilide nonsteroidal anti-inflammatory drug (NSAID)
      used in the treatment of various inflammatory diseases and chemically unrelated
      to other acidic NSAIDs, such as acetylsalicylic acid (ASA) and indomethacin
      (INDO). We investigated the effects of NIM and of its in vivo metabolite, 4
      hydroxy-NIM (OH-NIM), on the release of performed (histamine) and de novo
      synthesized mediators (sulfidopeptide leukotriene C4 [LTC4] and prostaglandin D2
      [PGD2]) from human basophils and mast cells isolated from lung parenchyma (HLMC)
      and skin (HSMC). Histamine release from basophils challenged with rabbit anti
      human IgE antibody (anti-IgE) was enhanced by preincubation with ASA or INDO
      (92.2 +/- 7.1% at 10(-3) M and 61.1 +/- 6.7% at 3 x 10(-6) M, respectively; P <
      .001). In contrast, NIM and its metabolite, OH-NIM (10(-6) to 10(-3) M), caused
      concentration-dependent inhibition (2.9 to approximately 60% and 3.7 to
      approximately 90%, respectively) of IgE-mediated histamine release from
      basophils. NIM and OH-NIM also inhibited histamine release from basophils induced
      by the Ca++ ionophore A23187 and different protein kinase C activators, such as
      12-O-tetradecanoyl-phorbol-13-acetate, bryostatin 1 and bryostatin 5. NIM and OH
      NIM also inhibited the IgE-mediated histamine release from HLMC (52.3 +/- 9.6%
      and 66.1 +/- 12.1% at 10(-3) M, respectively; P < .0001) and HSMC (67.3 +/- 3.7%
      and 77.7 +/- 12.0% at 10(-3) M, respectively; P < .0001) but had little or no
      effect on HLMC and HSMC activated by A23187. NIM (10(-6) to 10(-3) M) markedly
      inhibited the de novo synthesis of LTC4 from basophils, LTC4 and PGD2 from HLMC
      and PGD2 from HSMC. NIM and OH-NIM potentiated, whereas ASA and INDO reversed,
      the inhibitory effect of adenylate cyclase agonists, such as prostaglandin E1 and
      forskolin. In addition, NIM and OH-NIM reversed the enhancing effects of ASA and
      INDO on IgE-mediated histamine release from basophils.

PMID- 7505334
TI  - Effect of anti-inflammatory agents on ricin-induced macrophage toxicity.
AB  - The toxicity of ricin in susceptible cells is well characterized biochemically,
      but the pathophysiological implications of its toxicity and the immune response
      to ricin challenge in the lung are unknown. Incubating macrophage cell line with
      ricin (1 pM-10 nM) for 4 hours markedly inhibited 3H-leucine incorporation (acid
      insoluble) into protein (> 95%, at 1 nM) without affecting the acid-soluble
      radioactivity. In spite of increased uptake of total thymidine (141 +/- 13.5%)
      and total uridine (135 +/- 17.2%), DNA synthesis in ricin-treated cells was
      progressively inhibited although RNA synthesis was not affected. Fluocinolone (an
      anti-inflammatory glucocorticoid) pretreatment increased the ricin-induced
      inhibition of protein synthesis. The synergistic effect of fluocinolone on ricin
      induced protein synthesis inhibition was due to an increased binding (167%, p <
      0.01) and internalization (134 +/- 12%, p < 0.025) of ricin. Partial protection
      from ricin-induced inhibition of protein synthesis by indomethacin (nonsteroidal,
      anti-inflammatory agent) was due to decreased binding and internalization of
      ricin. These results show that macrophages are sensitive to ricin and that
      pharmacologically active drugs may regulate ricin's toxicity, perhaps by
      controlling synthesis and release of certain mediators of fast death.

PMID- 7505335
TI  - An imbalance of HU synthesis induces mucoidy in Escherichia coli.
AB  - Mutations in a number of loci, including the lon gene, dramatically increase the
      production of colanic acid capsular polysaccharide and render Escherichia coli K
      12 mucoid. The lon gene, which encodes an ATP-dependent protease, is localized at
      ten minutes on the E. coli map and is very closely linked to the hupB gene coding
      for one of the two subunits of the histone-like protein HU. Surprisingly the
      introduction of a multi-copy plasmid carrying either the hupB or hupA gene into a
      wild-type E. coli strain, results in the overproduction of one of the HU subunits
      and repression of the synthesis of the other without changing the overall
      concentration of HU, also renders the cells mucoid. As in a lon strain, the
      transcription of the cps genes, the structural genes for the synthesis of colanic
      acid, is induced dramatically. Protease Lon negatively regulates cps genes by
      destabilizing RcsA, a positive regulator of capsule synthesis. Regulation of HU
      synthesis does not affect the steady state level of Lon, as judged by Western
      blotting. The UV sensitivity of the hup transformed lon+ bacteria is identical to
      the lon+ parental strain, suggesting that Lon activity for the degradation of
      SulA in these cells is normal. Using lac operon fusions to cps gene promoters and
      to the rcsA promoter we show that the deregulation of HU synthesis does not by
      pass the positive regulatory action of RcsA and RcsB for the expression of cps
      genes but functions by stimulating RcsA synthesis.

PMID- 7505336
TI  - Effect of solvent on collective motions in globular protein.
AB  - Two molecular dynamics simulations on bovine pancreatic trypsin inhibitor (BPTI),
      have been made, one in vacuum, the other in water, in order to assess the effect
      of the solvent water on collective motions. Principal component analysis has been
      performed to determine collective modes, the principal components, which are
      assumed to behave as effectively independent harmonic oscillators. Projection of
      the protein's motion in water onto the plane defined by the first two principal
      components shows a clustering effect in the trajectory, absent in the vacuum
      trajectory. This is thought to be due to many local minima in the free energy
      surface caused by solute-solvent interactions. In order to assess the viscous
      effect of the solvent, friction coefficients for the principal components were
      determined by analyzing their velocity correlation functions in terms of the
      Langevin equation for an independent damped oscillator. Consistent with this
      analysis is that all modes have friction coefficients centered on the value of 47
      cm-1 in a range of +/- 10 cm-1. With this friction coefficient, all modes of
      effective frequencies below 23.5 cm-1 display overdamped motion. By assuming the
      harmonic approximation for the conformational energy surface for BPTI in vacuum
      to be valid for BPTI in water, and treating each mode as an independent damped
      oscillator with a friction coefficient of 47 cm-1, the shift to higher
      frequencies in the water spectrum relative to the vacuum spectrum could be almost
      exactly reproduced, indicating this shift is due solely to the viscous effect of
      the solvent. By analyzing the time correlation functions of the first four
      principal components it is found that they can be very well described as
      independent damped oscillators each with a friction coefficient of 47 cm-1.

PMID- 7505337
TI  - The role of RNA structure in determining RNase E-dependent cleavage sites in the
      mRNA for ribosomal protein S20 in vitro.
AB  - An RNA encompassing the 3' 147 residues of the mRNA for ribosomal protein S20 in
      Escherichia coli constitutes a naturally occurring degradative intermediate whose
      formation depends on RNase E. We have investigated the role of internal stem-loop
      structures in the RNase E-dependent cleavage which generates this product from
      S20 mRNA in a partially fractionated processing system in vitro. Individual stem
      loops have been removed by deletion or destabilized by point mutations. No single
      hairpin structure is absolutely required for RNase E-dependent cleavage at the
      site 147 residues from the 3' end of the RNA. Primary sequences or secondary
      structures 5' or 3' to this site exert only a modest influence on the specificity
      of cleavage but can strongly modify its rate. Moreover, mutations in the S20 mRNA
      which destabilize stems 5' or 3' to the prominent cleavage site also reveal
      several strong cryptic RNase E cleavage sites. These data greatly strengthen the
      hypothesis that RNase E is a single-strand specific endoribonuclease. Our data
      further demonstrate that stem-loop structures adjacent to the prominent cleavage
      site are unlikely to provide a site of recognition for RNase E. Rather, they
      appear to stabilize (or "anchor") the local secondary structure so that the
      cleavage site is single-stranded and to occlude alternative sites so that the
      initial products of cleavage resist further attack.

PMID- 7505338
TI  - Regulation of cardiac energy turnover by coronary flow: a 31P-NMR study.
AB  - The response of cytosolic phosphates ([ATP], [PCr], [Pi] and [ADP]) in rat hearts
      retrogradely perfused with different oxidizable substrates to increased workload
      induced by elevated coronary flow (CF) or by addition of inotropic agents has
      been investigated. Hearts were perfused with glucose (11 mM), pyruvate (5 mM),
      lactate (3 mM) or a combination of glucose (5.5 mM) and acetate (5 mM), octanoate
      (0.1 mM) or beta-hydroxybutyrate (5 mM). The initial [ATP]/[ADP] ratio was
      highest in pyruvate and lactate perfused hearts. Increasing the coronary flow 1.7
      fold (from c. 56 to 96 ml/min x g dry wt) resulted in an increase in pressure
      rate product (PRP) by 36-52% without significant changes in cytosolic phosphates.
      Dichloroacetate (1 mM), ruthenium red (2.5 micrograms/ml), or pre-treatment with
      theophylline (1 mM, 30 min) had no effect either functional or metabolic response
      to elevated CF in glucose-perfused hearts. Isoproterenol (Iso, 0.1 microM)
      infusion at maximal coronary flows lead to further elevation of PRP value by 36
      88% and the ratio of the maximal rate of relaxation to LV developed pressure ((
      dP/dt)m/LVDP) increased two-fold. Simultaneously, [PCr] decreased by 18-30%, [Pi]
      increased two-fold and ADP increased by 20-90% resulting in reduction of
      [ATP]/[ADP] by half and ATP affinity (A(ATP) = -delta G(ATP)) by 2.4-3.8 kJ/mol.
      In hearts perfused with acetate, octanoate and hydroxybutyrate in the presence of
      glucose, Iso addition resulted in intracellular pH decrease by 0.03-0.07 U and
      increase in lactate extrusion 1.5-2 times. In hearts perfused with glucose alone,
      decrease in PRP induced by perfusate Ca2+ reduction was associated with increase
      in PCr and decrease in Pi levels. These data show that coordinated regulation of
      energy supply and demand exerted by coronary flow/perfusion pressure does not
      depend on the availability of reducing equivalents but is rather controlled by
      oxygen supply and stretch-activated factors.

PMID- 7505339
TI  - Beta-adrenergic stimulation of cardiac non-myocytes augments the growth-promoting
      activity of non-myocyte conditioned medium.
AB  - Although the stimulatory action of catecholamines on the heart has been presumed
      to result exclusively from their direct effects on the cardiac myocytes, little
      work has been done addressing the effects of catecholamines on the supporting non
      myocytes of the heart. We have recently identified medium conditioned by neonatal
      rat cardiac non-myocytes (NMC-CM) as the source of a growth-promoting factor
      which leads to cardiac myocyte hypertrophy in culture, suggesting that these non
      myocytes may play an active role in myocardial growth. Since cardiac non-myocytes
      also contain adrenergic receptors (both alpha and beta) on their cell surface, we
      asked whether adrenergic stimulation of these non-myocytes could supplement the
      growth-promoting effect of NMC-CM. While isoproterenol (ISO, 0.2 microM) caused
      no increase in the per cell content of total protein in the non-myocytes,
      inclusion of ISO in the medium used in the production of NMC-CM augmented the
      growth promoting effects of this "ISOCM" over control CM. This increase was not
      seen with the alpha 1 adrenergic agonist phenylephrine suggesting that the
      stimulatory effect was specific to the beta-adrenergic receptor. Because TGF beta
      3 contains an upstream cAMP Response Element, we wonder whether its expression
      could respond to the increase in cAMP induced by ISO. Non-myocytes treated over
      72 h with ISO expressed increased steady state mRNA levels for TGF beta 3 but not
      that for the closely related TGF beta 1 over this time period. We believe that
      this is the first report indicating that a potential mechanism for the observed
      effects of beta-adrenergic stimulation on myocardial cells in culture and
      possibly relevant in vivo is the contribution of beta-stimulated factor(s)
      produced by non-myocytes which act in a paracrine fashion on myocardial cells.

PMID- 7505340
TI  - Changes in mitochondrial matrix free calcium in perfused rat hearts subjected to
      hypoxia-reoxygenation.
AB  - Reperfusion or reoxygenation of ischaemic or hypoxic cardiac tissue results in
      increases in total cell calcium and cell lysis both of which are dependent on
      mitochondrial function. Although changes which occur during this period of
      exposure of the tissue to hypoxia predispose the heart to take up calcium on
      reoxygenation, the mechanisms involved are not well understood. In the present
      study we have investigated the effects of hypoxia and reoxygenation on the
      concentration of intramitochondrial (matrix) free Ca2+ ([Ca2+]m) using
      mitochondria loaded in the intact heart with fura-2. During periods of up to 80
      min hypoxia, total tissue calcium content was unchanged. Over this period [Ca2+]m
      rose from an initial value of 156 +/- 26 nM to 360 +/- 33 nM and 574 +/- 62 nM at
      50 and 80 min of hypoxia, respectively; values that are within the expected
      physiological range for [Ca2+]m. Reoxygenation after 50 min hypoxia resulted in
      no further change in [Ca2+]m whereas reoxygenation after 80 min hypoxia resulted
      in a 10-fold increase in this parameter. These results provide clear evidence
      that [Ca2+]m increases during hypoxia and suggest that the ability of the cell to
      maintain Ca2+ homeostasis is lost on reoxygenation after prolonged hypoxia with
      the result that [Ca2+]m exceeds the normal physiological range.

PMID- 7505341
TI  - Effect of hyaluronidase on brain extracellular matrix in vivo and optic nerve
      regeneration.
AB  - In the rat, intracerebral injection of bacterial hyaluronidase resulted in the
      almost complete disappearance of hyaluronic acid (HA) and glial hyaluronate
      binding protein (GHAP) from cerebral hemispheres, brain stem, and cerebellum (but
      not from optic nerves and chiasm) starting 2-3 hr after the injection. HA and
      GHAP reappeared throughout the brain in characteristic patches 2-3 days after the
      injection. The patches gradually became confluent and after 12 days the brain
      appeared virtually normal. In normal rat optic nerve, staining for HA and GHAP
      ceased abruptly in the region of the lamina cribrosa. The retina was completely
      negative. HA and GHAP disappeared from hyaluronidase-injected optic nerve,
      chiasm, and contralateral optic nerve. In hyaluronidase-injected crushed optic
      nerves, regenerated axons were able to grow for short distances (about 500
      microns) into the distal stump undergoing Wallerian degeneration. No such growth
      was observed in saline-injected controls.

PMID- 7505342
TI  - Calcitonin induces a decreased Na+ conductance in identified neurons of Aplysia.
AB  - The ionic mechanism of the effect of extracellularly ejected calcitonin (CT) on
      the membrane of identified neurons R9 and R10 of Aplysia was investigated with
      voltage-clamp, micropressure ejection, and ion substitution techniques.
      Micropressure-ejected CT caused a marked hyperpolarization in the unclamped
      neuron. Heat-inactivated CT was without effect. Clamping the same neuron at its
      resting potential level (-60 mV) and re-ejecting CT with the same dose produced a
      slow outward current (Io(CT), 30-40 sec in duration, 4-6 nA in amplitude)
      associated with a decrease in input membrane conductance. Io(CT) was decreased by
      depolarization and increased by hyperpolarization. The extrapolated reversal
      potential of Io(CT) was approximately +10 mV. Io(CT) was sensitive to changes in
      the external Na+ concentration but not to changes in K+, Ca2+, and Cl-
      concentrations. Micropressure-ejected forskolin produced a slow outward current,
      which, like the current to CT, was associated with a decrease in input membrane
      conductance, and was sensitive to changes in the external Na+ concentration.
      Io(CT) was prolonged by bath-applied isobutylmethylxanthine (IBMX) but was not
      affected by 1-oleoyl-2-acetylglycerol (OAG) and calphostin C. Neither superfusion
      of the neuron with nordihydroguaiaretic acid (NDGA) nor superfusion with
      indomethacin caused any changes in Io(CT). These results suggest that
      extracellular CT can induce a slow outward current associated with a decrease in
      Na+ conductance, mediated by a receptor-controlled increase in intracellular
      cyclic adenosine 3',5'-monophosphate.

PMID- 7505344
TI  - [Expression of fibronectin receptor and vitronectin receptor in diseased human
      kidneys].
AB  - Expression of fibronectin and vitronectin receptors was studied in normal human
      kidney tissues and renal tissue biopsies from patients with several types of
      glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that
      fibronectin receptor was present along the glomerular capillary walls, and that
      vitronectin receptor was present in the vessel walls, but was almost absent from
      the glomerulus. In kidney tissues biopsied from patients with various renal
      diseases, expression of fibronectin and vitronectin receptors was correlated with
      increase in the mesangial expansion. Expression of these receptors was decreased
      in the sclerosed area and hyalinized glomeruli compared with normal tissues.
      Fibronectin and vitronectin receptors were occasionally colocalized in the
      glomeruli with fibronectin and vitronectin, respectively. In situ hybridization
      showed that fibronectin receptor mRNA and vitronectin receptor mRNA were
      expressed in the diseased glomeruli. These findings indicate that expression of
      fibronectin and vitronectin receptors was altered in human glomerulonephritis,
      and that integrin expression may be important in cell-matrix interaction in the
      diseased glomeruli.

PMID- 7505343
TI  - Modulation of the neurofibromatosis type 1 gene product, neurofibromin, during
      Schwann cell differentiation.
AB  - Neurofibromin, the product of the neurofibromatosis type 1 (NF1) gene, is a
      approximately 250 kDa protein expressed predominantly in cortical neurons and
      oligodendrocytes in the central nervous system (CNS) and sensory neurons and
      Schwann cells in the peripheral nervous system (PNS). To gain insight into the
      biological role of neurofibromin in Schwann cells, the modulation of NF1 gene
      expression in a Schwann cell line (MT4H1) stimulated to either proliferate or
      differentiate in response to agents that elevate intracellular cAMP was examined.
      Untreated cells and cells exposed to mitogenic doses of forskolin (1-10 microM)
      or 8-bromo-cAMP (0.1 mM) expressed low levels of NF1 mRNA and the protein was
      barely detectable. High doses of forskolin (100 microM) or 8-bromo-cAMP (1 mM)
      induced the expression of both myelin P0 protein and neurofibromin with an
      identical time course. Although NF1 mRNA levels peaked within 1-6 hr, the rise in
      neurofibromin was not apparent until 24-48 hr and peaked 72 hr after treatment.
      P0 and neurofibromin were also coinduced by cell-cell contact in high density,
      untreated cultures. Moreover, differentiation initiated by either cAMP
      stimulation or high density culture conditions was associated with predominant
      expression of the type 2 NF1 mRNA isoform. In contrast, type 1 NF1 mRNA isoform
      expression was observed in untreated Schwann cells or those stimulated with
      mitogenic doses of forskolin or 8-bromo-cAMP. A switch from the type 1
      neurofibromin that can efficiently downregulate p21-ras to the type 2 isoform
      with reduced activity may facilitate a p21-ras signaling pathway associated with
      Schwann cell differentiation.

PMID- 7505345
TI  - [Changes in coagulation and fibrinolytic factors observed during heparin
      urokinase-pulse combined therapy for nephritis resistant to conventional
      treatment in children].
AB  - Coagulation and fibrinolytic factors in the blood were measured during heparin
      urokinase (UK)-pulse combined therapy in order to investigate the background for
      the availability of the therapy. Five patients with nephritis resistant to
      conventional treatment were treated with this combined therapy (heparin: 350-450
      U/kg day, continuously i.v. during the therapy; UK: 5000 IU/kg/2 hrs, i.v., two
      times a day, for 3 days = 1 Kur; methylprednisolone 20 mg/kg/2hrs, d.i.v., for 3
      days = 1 Kur; 3 Kurs of UK and 3 Kurs of pulse were alternately administered). 1)
      Blood levels of alpha 2-plasmin inhibitor (alpha 2-PI) antigen were decreased and
      those of alpha 2-plasmin inhibitor.plasmin complex (alpha 2-PI. PmC) were
      elevated during 3 Kurs of UK administration. Accordingly, activation of the
      fibrinolytic system was confirmed during the combined therapy, suggesting that
      both alpha 2-PI and alpha 2-PI.PmC were relevant in monitoring the fibrinolytic
      state in blood. 2) Both tissue-plasminogen activator (t-PA) and plasminogen
      activator inhibitor-1 (PAI-1) levels were sustained continuously in the elevated
      levels in the blood during both UK administration and pulse therapy. This
      movement of t-PA and PAI-1 was independent of that of the other fibrinolytic
      factors, such as alpha 2-PI,alpha 2-PI.PmC and plasminogen. 3) Inflammatory
      reactants such as fibrinogen, alpha 2-PI,alpha 2-macroglobulin and alpha 1
      antitrypsin decreased more significantly during this heparin-urokinase-pulse
      combined therapy than during our previous combined therapy consisting of only
      heparin and urokinase. Therefore, we conclude that the anti-inflammatory effect
      was reinforced by adding the pulse therapy and that the combined therapy had some
      effect on the release of t-PA from vascular endothelial cells.

PMID- 7505346
TI  - [Liver impairment in kidney transplant recipients. 1. Prevalence and clinical
      significance of hepatitis C].
AB  - The prevalence and the clinical significance of hepatitis C (HCV) infection in
      recipients of kidney transplantation was assessed using second generation anti
      HCV antibody (anti-HCV-2). Out of 88 patients whose preoperative sera were
      available for anti-HCV-2 determination, 27 patients (30.7%) were positive.
      Transfusion units were significantly larger and the duration of hemodialysis was
      significantly longer in the patients with anti-HCV-2 than those without. In 10
      patients whose preoperative sera were negative for anti-HCV-2, seroconversion was
      documented after the operation, so that the postoperative positive rate of anti
      HCV-2 increased to 42.9% (39/91). Seroconversion from positive to negative was
      observed in only one patient. Out of 91 patients who were followed-up at least 3
      months after operation, 66 patients (72.5%) developed liver dysfunction.
      According to the criteria of non-A, non-B post-transfusion hepatitis established
      by the Japanese Society of Digestive Disease, 31 of 66 patients (34.1%) were
      diagnosed as "definite", 21 patients (23.1%) as "suspicious". The anti-HCV-2
      positive rate was 90.3% in the "definite" group, which was significantly higher
      than the other groups. Liver dysfunction in the patients with anti-HCV-2 had a
      tendency for a chronic or prolonged course. Out of 20 patients in whom liver
      dysfunction continued for more than 1 year, 18 patients were positive for anti
      HCV-2. It is concluded from this study that the prevalence of hepatitis C is very
      high in kidney transplant recipients with HCV as the main and most important
      etiologic factor of liver dysfunction, especially in chronic liver impairment.

PMID- 7505348
TI  - Renal vascular induction of TGF-beta 2 and renin by potassium depletion.
AB  - Recently, we have found that transforming growth factor (TGF)-beta 2 and renin
      are abundantly expressed in the juxtaglomerular apparatus (JGA) of dehydrated
      mice. Since potassium (K+) depletion also stimulates renin and induces
      hypertrophy of the JGA, we examined the ability of this maneuver to stimulate TGF
      beta isoforms and renin in renovascular tissue and the JGA of young rats. Sprague
      Dawley rats (50 +/- 5 g) were fed either a control diet or a potassium-deficient
      diet (< 0.05% K+) for 7, 16, or 21 days. As a control for TGF-beta and renin
      stimulation, an additional group of animals was fed a normal diet but was water
      deprived for three days. Potassium-depleted animals experienced severe growth
      retardation but kidney weight increased significantly. Potassium depletion
      induced both TGF-beta 2 and renin immunoreactivity in renal arterioles and the
      JGA but had no effect on TGF-beta 1 and TGF-beta 3 isoforms. To determine the
      role of circulating angiotensin II in the stimulation of TGF-beta 2 by potassium
      depletion, a group of potassium-depleted rats received enalapril (100 mg/liter)
      in the drinking water. The addition of converting enzyme inhibitor increased both
      the intensity of TGF-beta 2 and renin staining as well as the number of cells
      positively stained. Our results demonstrate that K+ depletion induces TGF-beta 2
      and renin in renal arterioles and in the JGA. Furthermore, circulating
      angiotensin II is not responsible for the increase in the local expression of TGF
      beta 2. These findings suggest that TGF-beta 2 may be an important mediator of
      JGA hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505347
TI  - [A case of type II cryoglobulinemia involving glomerulopathy associated with
      hepatitis C antibody].
AB  - We reported a case of type II cryoglobulinemia involving glomerulopathy
      associated with HCV-induced liver cirrhosis. The patient was a 57-year-old woman.
      Her past history included chronic hepatitis at 51 years and rheumatoid arthritis
      at 53 years of age. At 46 years, an erythematous lesion appeared on her legs,
      which was diagnosed as allergic vasculitis by skin biopsy. At 50 years,
      proteinuria, hematuria and hypertension were recognized. The next year, the first
      renal biopsy was performed and showed membranoproliferative glomerulonephritis
      (MPGN). Recently, the edema of her legs has progressed, and the laboratory data
      showed proteinuria, hematuria, hypocomplementemia, rheumatoid factor positivity,
      and increase of monoclonal IgG kappa chain. The second renal biopsy revealed an
      endocapillary proliferative glomerulonephritis-like lesion with marked
      infiltration of monocytes and macrophages. The subendothelial deposit showed a
      fine fibril-like pattern. She was treated with steroids and double filtration
      plasmapheresis (DFPP) therapy, but the treatment was not very effective. She died
      of liver cirrhosis, which was probably induced by hepatitis C virus (HCV), and
      sepsis. Generally, the patients of type II cryoglobulinemia often showed HCV
      antibody positivity, pointing to HCV as an etiological factor. In this case,
      renal biopsy was performed twice in the same patient, and the histologic findings
      suggest the clinicopathological course of cryoglobulinemia.

PMID- 7505349
TI  - [The surgical treatment of pancreatic carcinoma (a retrospective study)].
AB  - The authors report the data from the surgical treatment of 426 patients with
      pancreatic carcinoma, treated at the Academy of Medicine-General and Operative
      Surgery, within the period 1983-1992, as well as from their own material,
      consisting of 70 right-sided resectio of the pancreatis, done within the period
      1978-1992. The patients with explorative laparatomies constituted 10.8% and had
      postoperative lethality 15.2%. Palliative operations were 73%, with postoperative
      lethality 13.2% and average survival 6.47 months. The radically operated patients
      constituted 16.19%, with postoperative lethality 14.28% in the general series and
      7.14% in the personal series and postoperative survival 18.7 months. From the
      radically operated with a right-sided localization of the process 10.7% patients
      had 5 years survival. The early lethality of the left-sided resectio was 0% and
      the postoperative survival--5-10 months.

PMID- 7505350
TI  - [The surgical treatment of carcinoma of the extrahepatic bile ducts].
AB  - The authors have carried out a retrospective analysis of 157 patients with Ca in
      the extrahepatic biliary system, treated at the Clinic for Hepato-Biliary and
      Pancreatic Surgery within the period 1982-1992. From them 68 patients (43.31%)
      were with Ca in vesicule biliary and with Ca in the biliary tracts--89 patients
      (56.69%). The ratio men:women was respectively 1:4.67 and 1.12:1. The medium age
      of the patients was 63.08 years. In the group of the patients with Ca in biliary
      tracts the carcinoma was located in the upper third in 20.22% of the cases, in
      the middle third--in 24.72%, in the distal third--in 55.06%. Radical operations
      were made in 31.46% of the patients, with lethality 28.57%, whereas the
      postoperative lethality of the patients with duodeno-hemipancreatectomy was
      6.67%, and the average postoperative survival was 32 months. The palliative
      operated patients constituted 65.17% in the general series, with lethality 15.52%
      and average postoperative survival 10.4 months. The explorative laparatomies
      constitute 3.37% from the operated patients. The total operative lethality was
      19.1%. In the article the authors discussed the diagnostical methods, stated the
      preference for echography, computer axial tomography and retrograde cholangio
      pancreatography in the mentioned sequence. The endoscopic procedures were
      discussed as and alternative for the non-resectable carcinomas of the biliary
      tracts.

PMID- 7505351
TI  - Comparative evaluation of the antihypertensive efficacy of once-daily amlodipine
      versus nitrendipine with 24-hour ambulatory blood pressure monitoring in
      essential hypertension.
AB  - We compared the antihypertensive efficacy of once-daily amlodipine (AM) versus
      nitrendipine (NTR) by 24-h ambulatory blood pressure monitoring (24-h ABPM) in 32
      patients with mild to moderate essential hypertension (EH). After a 2-week single
      blind, placebo run-in period, patients were randomized in a double-blind,
      parallel fashion: 14 received AM 5 mg and 18 NTR 10 mg. After 2 weeks, dose was
      adjusted if necessary (AM 10 mg or NTR 20 mg) and continued for another 6-week
      period. At the end of the placebo period and during the last week of treatment,
      patients underwent 24-h ABPM. Initial office BP mean values were similar in both
      groups (169.8 +/- 14/102.5 +/- 6 vs. 167.1 +/- 14/98.7 +/- 5 mm Hg, respectively,
      p = NS). A comparable decrease in office mean values of systolic BP (SBP, -22.3
      +/- 13 vs. -19.1 +/- 16 mm Hg) and diastolic BP (DBP, -12.0 +/- 5 vs. -8.1 +/- 8
      mm Hg) was observed. Nevertheless, 24-h ABPM mean values differed significantly
      between patients treated with AM or NTR with regard to 24-h SBP (120.0 +/- 10 vs.
      132.5 +/- 1 mm Hg, p = 0.01). Moreover, the average decrease in 24-h SBP (-19.3
      +/- 6 vs. -5.2 +/- 11 mm Hg, p = 0.0036) and 24-h DBP (-10.7 +/- 4 vs. -3.7 +/- 6
      mm Hg, p = 0.0047) was higher in the AM group, with no changes in 24-h heart rate
      (HR). At equivalent once-daily dosage, AM was more effective than NTR in
      decreasing BP assessed by 24-h ABPM.

PMID- 7505352
TI  - RWJ-24517, a positive inotropic agent, has novel effects on action potentials in
      guinea pig myocardium.
AB  - RWJ-24517 is a positive inotropic agent whose mechanism of action is under
      investigation. We examined the effects of RWJ-24517 on guinea pig papillary
      muscle action potentials and myofilament response to Ca2+. RWJ-24517 increased
      the fast action potential duration (APD) in a dose-dependent fashion but had no
      effect on the myofilament response. Tetraethylammonium (TEA 10 mM), which in
      itself slightly prolonged the control AP, completely blocked the increase in
      APD75 (APD at 75% of repolarization) and suppressed the increase in APD25 induced
      by RWJ-24517 (10 microM). Verapamil (5 microM) had little effect on control APs
      but did decrease the prolongation of the AP induced by RWJ-24517. The increase in
      APD25 induced by RWJ-24517 was not completely blocked by TEA even with addition
      of verapamil or 4-aminopyridine (2 mM). RWJ-24517 enhanced Ca(2+)-dependent slow
      APs elicited by 0.1 microM isoproterenol in preparations depolarized by high
      extracellular K+ (25 mM), but had no effects on slow APs elicited by 10 mM TEA.
      These results suggest that the primary electrophysiologic effect of RWJ-24517 is
      a substantial AP prolongation, which appears to occur largely through a mechanism
      which is likely to involve inhibition of Ca(2+)-dependent K+ channels. It also
      appears to have additional effects on some other channels (possibly Na+
      channels), which may contribute to the positive inotropic action of RWJ-24517.

PMID- 7505353
TI  - Superior activity of a thromboxane receptor antagonist as compared with aspirin
      in rat models of arterial and venous thrombosis.
AB  - We determined the effects of aspirin and a novel thromboxane A2/prostaglandin
      endoperoxide (TP)-receptor antagonist, BMS-180291, on thrombosis and bleeding
      times in skin and mesenteric arteries. In anesthetized rats, occlusive thrombosis
      was induced in the carotid artery by topical application of ferrous chloride and
      in the vena cava by blood flow stasis combined with either infusion of
      thromboplastin or hypotonic saline. Aspirin (1, 10, and 50 mg/kg) did not reduce
      arterial or venous thrombus weight significantly. BMS 180,291 (150
      micrograms/kg/min) decreased arterial thrombus weight and hypotonic saline
      induced caval thrombus weight by 58 and 57%, respectively. BMS-180291 lacked
      antithrombotic activity at a lower dose (50 micrograms/kg/min) and failed to
      inhibit thromboplastin-induced caval thrombosis. BMS-180291 (150
      micrograms/kg/min) significantly reduced arterial thrombus weight by 40% when
      plasma epinephrine concentration was increased to 5 ng/ml. BMS-180291 and aspirin
      produced increases of only < or = 30% in bleeding times. These results
      demonstrate that BMS-180291 has antithrombotic activity in experimental aspirin
      resistant arterial and venous thrombosis. Both aspirin and BMS-180291 have only
      modest effects on small artery hemostasis in rats.

PMID- 7505354
TI  - Electrophysiologic effects of a potassium channel activator (pinacidil) on
      repolarization parameters in healthy volunteers: a surface ECG study.
AB  - About a quarter to a third of patients receiving pinacidil, a new cyanoguanidine
      vasodilator, show ECG changes, in particular T-wave modifications that sometimes
      mimic myocardial ischemia. To investigate these changes, we performed a
      randomized placebo-controlled trial in 10 carefully selected, healthy subjects
      who received single oral doses of either pinacidil (25 mg), quinidine (330 mg),
      and placebo. Quinidine, which induces specific modifications to the surface ECG
      signal, was used as an internal control. The complete experimental design
      involved five consecutive administrations of the drugs in random order: pinacidil
      (twice), quinidine (twice), and placebo (once), separated by a week-long washout
      period. Electrophysiologic data acquisition and signal analysis were performed
      with the Lyon vectocardiographic processing system. Pinacidil decreased T-wave
      amplitude (-0.26 +/- 0.1 mV) significantly as compared with placebo (-0.14 +/-
      0.06 mV), but did not change the duration of the T-wave. Although the cardiac
      rate increased with pinacidil, the QTc interval remained constant. Conversely,
      quinidine did not modify the RR interval but significantly increased duration of
      the T-wave (+67 +/- 20 ms) and QTc interval (+53 +/- 13 ms) as compared with
      placebo (+17 +/- 13 and +18 +/- 11 ms). In addition, no specific ischemic changes
      to the T-loop were observed with pinacidil. The modifications to the surface ECG
      signal caused by pinacidil appear to be drug-specific and related to its
      electrophysiologic properties rather than involving any ischemic mechanism. Such
      an approach may be useful for describing morphologic ECG changes caused by new
      drugs and identifying possible underlying electrophysiologic mechanism(s), which
      should then be confirmed in further studies.

PMID- 7505355
TI  - Comparative assessment of ibutilide, D-sotalol, clofilium, E-4031, and UK-68,798
      in a rabbit model of proarrhythmia.
AB  - Class III agents have been associated with development of a polymorphic
      ventricular tachycardia (PVT) known as torsades de pointes. We compared the class
      III agent ibutilide, which prolongs repolarization through enhancement of an
      inward sodium current, with the potassium channel blockers E-4031, UK-68,798,
      clofilium, and D-sotalol for proarrhythmic effects in an anesthetized rabbit
      model. In these animals, prolongation of repolarization during alpha 1
      stimulation with methoxamine produces early after depolarizations (EADs) and a
      pause-dependent torsades de pointes-like PVT. Agents were compared over dosage
      ranges that produced maximal increases in QTc interval and monophasic action
      potential duration (MAPD). PVT typically developed after atrioventricular (A-V)
      conduction block and slowing of heart rate (HR), and was preceded by development
      of repolarization arrhythmias characterized by EADs and triggered activity
      producing extrasystolic beats. Ibutilide administration resulted in significantly
      lower EAD amplitudes and a lower incidence of repolarization arrhythmias and PVT
      as compared with administration of other class III agents. The percentage of
      rabbits developing PVT for each agent was ibutilide 12%, D-sotalol 70%, E-4031
      56%, UK-68,798 69%, and clofilium 80%. Rabbits receiving saline vehicle instead
      of a class III agent never developed conduction or repolarization abnormalities
      or PVT. Under the conditions of this study at doses that generate maximal class
      III effects, ibutilide produces lesser increases in QTc interval and MAPD, and
      EADs of lower amplitude, resulting in a lower incidence of repolarization
      arrhythmias and PVT as compared with other class III agents.

PMID- 7505356
TI  - Antishock effect of U-67,590A, methylprednisolone suleptanate, associated with
      restoration of lowered vascular reactivity in endotoxemic rats.
AB  - We wished to investigate the modulating effects of a glucocorticoid on mortality
      and sustained hypotension in endotoxemic rats in conjunction with in vitro study
      of responses of isolated aorta to KCl, norepinephrine (NE), and acetylcholine
      (ACh). Endotoxemia was induced by intravenous (i.v.) bolus injection of 50 mg/kg
      Escherichia coli endotoxin in rats, resulting in high mortality. Pretreatment
      with U-67,590A, methylprednisolone suleptanate, at a dose of 9 mg/kg resulted in
      100% survival; the survival rate of saline-treated controls was 21%. Isolated rat
      aorta that had been treated with endotoxin for 4 h showed decreases in
      contractile responses to KCl and NE and in relaxing response to ACh. Similar
      attenuation of contractile responsiveness was observed in endothelium-denuded
      preparations. Addition of endotoxin to the in vitro tissue bath did not inhibit
      the responses in a 4-h period. Pretreatment with U-67,590A inhibited the late
      gradual decrease in blood pressure (BP) but not the early hypotensive response to
      endotoxin. The responses to KCl or NE of aorta isolated 4 h after the endotoxin
      injection remained suppressed in U-67,590A-treated rats but were restored in 24
      h. These results suggest that endotoxemia impairs the endothelium moderately, but
      this does not account for either reduced reactivity of vascular smooth muscle to
      vasoconstrictor agents or the sustained hypotension. The steroid inhibits
      endotoxemia-induced mortality and sustained hypotension.

PMID- 7505357
TI  - Comparison of the effects of cocaine and its metabolites on cardiovascular
      function in anesthetized rats.
AB  - Hemodynamic and cardiac-electrophysiologic effects of cocaine and its metabolites
      were measured in 18 groups (n = 6 each) of anesthetized, artificially ventilated
      rats during continuous intravenous (i.v.) infusions at three different doses
      (0.15, 0.45, and 1.5 mg/kg/min). At the highest dose, cocaine decreased blood
      pressure (BP) and heart rate (HR), while QRS duration, an index of cocaine's
      local anesthetic effect, was increased. Cocaethylene, a metabolite produced after
      coadministration of cocaine and ethanol, had effects comparable to those of
      cocaine. The cocaine metabolite norcocaine produced a decrease in BP at the lower
      dose that reversed to a small increase at the higher dose. The highest dose of
      norcocaine clearly decreased HR and increased QRS duration. The increases in QRS
      duration observed for cocaine, cocaethylene, and norcocaine were reversed by
      sodium bicarbonate. The cocaine metabolites benzoylecgonine and ecgonine methyl
      ester increased BP at the higher doses without affecting either HR or QRS
      duration. These results suggest that the spectrum of effects produced by cocaine
      are not necessarily mimicked by its metabolites. In particular, accumulation of
      the persistent, active metabolites benzoylecgonine and ecgonine methyl ester may
      contribute to delayed-onset, cocaine-related toxicity.

PMID- 7505358
TI  - Cardioprotective effects of the cyanoguanidine potassium channel opener P-1075.
AB  - P-1075 is a cyanoguanidine ATP-sensitive potassium channel opener (KATP) that
      relaxes smooth muscle and shortens myocardial action potential duration (APD) at
      concentrations in the nanomolar range. Most KATP openers have antiischemic
      potencies in the micromolar range. We wished to determine if the relatively high
      cardiac potency of P-1075 could be translated into high antiischemic potency.
      Isolated rat hearts were pretreated with 10-300 nM P-1075 followed by 25-min
      global ischemia and 30-min reperfusion. Before ischemia, P-1075 had little effect
      on cardiac function, although it did increase coronary flow. During ischemia, P
      1075 significantly increased time to contracture in a concentration-dependent
      manner (EC25 = 57 nM). P-1075 also improved recovery of contractile function
      significantly and reduced lactate dehydrogenase (LDH) release during reperfusion
      (at concentrations > or = 60 nM). Treatment with 75 nM P-1075 both before and
      after ischemia did not add to the protective effects observed after preischemic
      treatment. Treatment with P-1075 only during reperfusion was not
      cardioprotective. The protective effects of P-1075 were completely abolished by
      the KATP blocker glyburide (100 nM). In addition, P-1075 relaxed methoxamine
      constricted aorta with a higher potency relative to antiischemic potency. Thus, P
      1075 has cardioprotective effects similar to that of other reference KATP
      openers, except that P-1075 is approximately 100-fold more potent relative to
      most other tested KATP openers. These results demonstrate that P-1075 is the
      first KATP opener that protects ischemic myocardium at nanomolar concentrations.

PMID- 7505359
TI  - Selective inhibition of pressor and haemodynamic effects of NG-nitro-L-arginine
      by halothane.
AB  - We investigated the characteristics of inhibition by halothane of the pressor
      responses to NG-substituted L-arginine derivatives, nitric oxide (NO) synthase
      inhibitors. Intravenous (i.v.) bolus injections of NG-nitro-L-arginine (L-NNA, 1
      32 mg/kg), NG-nitro-L-arginine methyl ester (L-NAME, 0.4-12.8 mg/kg),
      norepinephrine (NE, 0.25-8 micrograms/kg) and angiotensin II (AII, 0.02-0.64
      micrograms/kg) each caused dose-dependent pressor responses in conscious rats.
      Halothane attenuated responses to the highest dose of NE and AII by approximately
      18% but completely abolished responses to L-NNA and L-NAME. The haemodynamic
      effects of L-NNA were further examined by the microsphere technique in two groups
      of conscious rats and two groups of halothane-anaesthetized rats. An i.v. bolus
      injection of L-NNA (16 mg/kg) in conscious rats increased mean arterial pressure
      (MAP) and total peripheral resistance (TPR) and reduced heart rate (HR) and
      cardiac output (CO). These changes were associated with reduced conductance in
      all vascular beds, with the greatest reduction in the lungs and the least in the
      liver. In halothane-anaesthetized rats, L-NNA caused significant but markedly
      less change in MAP, HR, TPR, and CO as compared with those in conscious rats. The
      vasoconstrictor effects of L-NNA were attenuated by halothane in all beds except
      liver and spleen, with the greatest inhibition in heart. Our results suggest that
      NO plays a role in maintenance of peripheral vascular resistance and that
      halothane selectively and "noncompetitively" inhibits the vasoconstrictor effects
      of NO synthase inhibitors.

PMID- 7505360
TI  - Comparison of angiotensin-converting enzyme inhibition with angiotensin II
      receptor antagonism in the human forearm.
AB  - The object of this study was to differentiate losartan, an AT1-selective
      angiotensin II (ANG II) receptor antagonist, from enalapril, an angiotensin
      converting enzyme (ACE) inhibitor, by measuring forearm vascular responses to AI,
      AII, and bradykinin. Eight healthy men were studied in a randomised, 4-period
      crossover study in which placebo, enalapril (10 mg), losartan (20 mg) and
      losartan (100 mg) were given double-blind on separate occasions. Forearm blood
      flow was measured by venous occlusion plethysmography during sequential infusions
      of ANG I, ANG II, and bradykinin into the brachial artery 4-6 h after dosing.
      Analysis of variance for repeated measures indicated that losartan inhibited
      constriction to ANG I and ANG II (both p < 0.02) in a dose-dependent manner
      without significantly influencing vasodilator responses to bradykinin. Enalapril
      (10 mg) inhibited AI similarly to losartan 100 mg without significantly
      influencing responses to angiotensin II, and augmented vasodilator responses to
      bradykinin (p < 0.0001). In human forearm vasculature, oral losartan (20-100 mg)
      inhibits vasoconstriction to ANG I and ANG II without significantly influencing
      bradykinin-induced vasodilation, whereas enalapril selectively inhibits ANG I
      induced vasoconstriction while potentiating the vasodilator effect of bradykinin.

PMID- 7505361
TI  - Effects of spiraprilat, an angiotensin-converting enzyme inhibitor, on
      anesthetized dogs in a new model of acute left ventricular failure.
AB  - Spiraprilat, a new angiotensin-converting enzyme (ACE) inhibitor, was compared
      with enalaprilat for its ability to improve left ventricular (LV) function and
      metabolism in anesthetized open-chest dogs with a new model of acute LV failure
      (ALVF) induced by embolization of the left coronary artery with 50 microns
      plastic microspheres followed by intravenous (i.v.) infusion of methoxamine. With
      this procedure, LV end-diastolic pressure (LVEDP) increased from 4.2 +/- 0.7 to
      12.8 +/- 1.3 mm Hg and remained at approximately 12 mm Hg throughout the
      experiment. Cardiac output (CO) decreased from 1.25 +/- 0.12 to 0.79 +/- 0.06 and
      0.55 +/- 0.02 L/min at 30 and 90 min after methoxamine infusion, respectively.
      LVdP/dtmax and dP/dt/P decreased, while total peripheral resistance (TPR)
      increased. These hemodynamic changes indicated establishment of stable ALVF of a
      moderate degree. Moreover, decreases in myocardial lactate consumption and
      contents of creatine phosphate in the myocardium indicated the existence of
      moderate ischemia. The new ACE inhibitor, spiraprilat, as well as enalaprilat (30
      micrograms/kg i.v.) effectively decreased mean aortic pressure (30%), LVEDP
      (20%), and TPR (30%) and increased stroke volume (SV) CO, and dP/dt/P. Both
      agents decreased myocardial oxygen consumption (20%) and caused a significant
      increase in myocardial creatine phosphate contents. These data indicate that the
      beneficial effects of both inhibitors extended not only to LV function but also
      to myocardial energy metabolism in ALVF.

PMID- 7505362
TI  - Distribution of neurally activated postjunctional adrenoceptors in cat forelimb
      vasculature.
AB  - We assessed the relative contribution of postjunctional alpha-adrenoceptor
      subtypes in neurally evoked vasoconstrictor responses in the forelimb of
      anesthetized cats. Preganglionic stimulation of the thoracic sympathetic nerve
      trunk produced frequency-related decreases in blood flow of the entire forelimb
      as measured by ultrasonic flowmetry as well as vasoconstriction in the digital
      cutaneous bed as measured by laser-Doppler flowmetry. Vasoconstrictor responses
      were not altered significantly by intravenous (i.v.) treatment with propranolol
      (1 mg/kg) or atropine (1 mg/kg). In the entire limb, prazosin, (3-100
      micrograms/kg i.v.) was a more potent antagonist of neurally evoked responses as
      compared with rauwolscine. In contrast, rauwolscine (10-300 micrograms/kg i.v.)
      was a more effective antagonist in the cutaneous bed. Combined treatment with
      both prazosin and rauwolscine was far more effective than either antagonist given
      alone in blocking vasoconstriction regardless of the measurement site. Moreover,
      basal cutaneous blood flow was increased by rauwolscine but not by prazosin.
      These results suggest that both subtypes of postsynaptic alpha-adrenoceptors are
      activated by sympathetic nerve stimulation. In the cutaneous bed, alpha 2
      adrenoceptors appear to predominate. In addition, cutaneous vascular tone also
      appears to be regulated by hormonal alpha 2-adrenoceptor activation in cats.

PMID- 7505363
TI  - Continuous versus intermittent nitroglycerin administration in experimental heart
      failure: vascular relaxation and radioligand binding to adrenoceptors and ion
      channels.
AB  - Continuous nitroglycerin (NTG) administration causes pharmacologic tolerance in
      humans and animals, whereas intermittent dosing is capable of avoiding or
      reducing tolerance development. The mechanism of NTG-induced hemodynamic
      tolerance may involve specific vascular desensitization and/or neurohormonal
      compensation. We compared effects of long-term (10 days) NTG administration
      (continuous or intermittent 12 h on/12 h off transdermal dosing, 10
      micrograms/min) to rats with congestive heart failure (CHF) on radioligand
      binding from selected tissues. Tension responses in isolated blood vessels,
      plasma renin activity (PRA), plasma Na+ and K+ concentrations were also
      determined. The maximal binding values (Bmax) for [3H]glyburide and [3H]PN 200
      110 in homogenates of left ventricle, right ventricle, and brain were not
      significantly different after NTG administration (continuous or intermittent), as
      compared with control. Intermittent, but not continuous, NTG caused significant
      increases in beta-adrenoceptor densities in the left ventricle, as judged by
      [3H]dihydroalprenolol binding (Bmax values: intermittent NTG 34.5 +/- 4.8,
      continuous NTG 24.4 +/- 2.6, placebo control 20.9 +/- 2.9 fmol/mg protein); Kd
      values for all ligands were not significantly altered by NTG administration. Both
      intermittent and continuous NTG increased the vascular contractile response to
      phenylephrine in isolated rat thoracic aorta. Slight reductions (two- to four
      fold shifts in EC50 values) in thoracic aorta relaxant response to NTG were
      observed in both treatment groups as compared with control. Intermittent and
      continuous NTG administration caused selective changes in beta-adrenoceptor
      density and vascular response. These changes may contribute partly to the
      phenomenon of pharmacologic tolerance after chronic nitrate administration.

PMID- 7505364
TI  - Receptor mechanism of thrombin-induced endothelium-dependent and endothelium
      independent coronary vascular effects in dogs.
AB  - We previously reported that thrombin produces endothelium-dependent relaxation
      and endothelium-independent constrictions in canine coronary arteries. To
      determine whether these opposing vascular effects of thrombin are mediated by the
      same receptor mechanism, but at different cell types, we investigated the effects
      of thrombin receptor agonist peptide (TRAP) on isolated canine coronary arteries
      with and without intact endothelium. In coronary arteries with intact
      endothelium, addition of 0.01-3.0 microM TRAP, a 14-amino acid residue peptide
      (SFLLRNPNDKYEPF) homologous to the newly exposed N-terminus after cleavage of the
      cloned human thrombin receptor, produced rapid, dose-dependent relaxation (Emax =
      -89.6 +/- 2.3%, n = 26). Threshold concentration was 0.03 microM, and IC50 value
      was 0.3 microM. Mechanical disruption of the endothelium completely abolished the
      TRAP-induced relaxation; instead a dose-dependent contraction was observed.
      Expressed as a percentage of the maximum 70 mM KCl-induced contraction, the
      maximum contraction observed with 3 microM TRAP was 62.0 +/- 4.1% (n = 32).
      Pretreatment of endothelium-intact coronary arteries with either 3 microM
      hemoglobin or 0.25 mM NG-monomethyl-L-arginine (L-NMMA), specific inhibitors of
      endothelium-derived relaxing factor or nitric oxide (EDRF/NO), also inhibited the
      relaxation and unmasked the constrictor effect. The pharmacokinetic
      characteristics of the opposing coronary vascular effects of TRAP are similar to
      those observed with thrombin, but specific thrombin inhibitors, such as hirudin
      and D-phenylalanyl-prolyl-L-arginine chloromethyl ketone (PPACK), which inhibit
      both thrombin relaxant and constrictor effects, had no effect on TRAP-induced
      responses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505365
TI  - Pharmacology of SC-52458, an orally active, nonpeptide angiotensin AT1 receptor
      antagonist.
AB  - We describe the pharmacologic properties of SC-52458, 5-[(3,5-dibutyl-1H-1,2,4
      triazol-1-yl)methyl]-2-[2-(1H-tetrazol - 5-ylphenyl)]pyridine, a novel nonpeptide
      angiotensin II (AII) receptor antagonist. SC-52458 was a potent inhibitor of
      [125I]AII binding to AT1 receptors in rat adrenal cortex and uterine smooth
      muscle membranes (IC50 values of 2.8 and 6.9 nM, respectively). Contraction of
      rabbit aortic rings by AII was antagonized by SC-52458 in a competitive and
      reversible manner (pA2 of 8.18). SC-52458 had no effect on the activity of
      angiotensin converting enzyme (ACE) or renin in vitro. In normotensive rats,
      administration of SC-52458, either intravenously (i.v.) or by gavage, inhibited
      the pressor response to AII. Daily treatment with SC-52458 at 20, 30, and 50
      mg/kg by gavage for 4 days decreased blood pressure (BP) in conscious,
      spontaneously hypertensive rats (SHR). Further studies in renal-artery ligated
      rats and sodium-deficient dogs demonstrated that oral administration of SC-52458
      decreased BP and that this activity was correlated with significant plasma levels
      of the compound. SC-52458 is an orally active, competitive AT1-receptor
      antagonist with antihypertensive properties.

PMID- 7505366
TI  - Sodium nitroprusside, an endothelium-derived relaxing factor congener, increases
      platelet cyclic GMP levels and inhibits epinephrine-exacerbated in vivo platelet
      thrombus formation in stenosed canine coronary arteries.
AB  - Sodium nitroprusside (SNP), a nitrosovasodilator, increases platelet cyclic GMP
      levels and inhibits platelet activity in vitro. The antiplatelet properties of
      SNP are not well established in vivo, however, and consequently are not
      appreciated by clinicians. In our established model of mechanically stenosed
      canine coronary arteries (MSCA) with intimal damage, periodic acute platelet
      thrombus formation (APTF) occurs, followed by embolization distally, which then
      causes cyclic flow reductions (CFRs) in coronary blood flow. Aspirin (ASA)
      abolished platelet-mediated CFRs in our model, but they recur when epinephrine
      (EPI) is infused (0.2 microgram/kg/min). SNP was given continuously intravenously
      (i.v.) to 17 dogs with MSCA; CFRs were abolished in all dogs by SNP at 4.4 +/-
      2.7 micrograms/kg/min (mean +/- SD). Mean arterial blood pressure (MAP) decreased
      by 19 +/- 9 mm Hg (p < 0.001) from control, while heart rate (HR) increased 35 +/
      20 beats/min (p < 0.001). Platelet cyclic GMP levels were 2.9 +/- 1.1 pmol/10(8)
      platelets before SNP infusion, and increased to 4.3 +/- 1.6 pmol/10(8) platelets
      (p < 0.05) when CFRs were abolished. CFRs were not renewed during the continued
      SNP infusion when EPI was infused at 0.2 microgram/kg/min for 20 min in 11 dogs,
      but CFRs returned within 5-25 min after the SNP infusion was terminated. The
      return of CFRs occurred together with a decrease in platelet cyclic GMP levels to
      3.3 +/- 1.4 pmol/10(8) platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505367
TI  - Role of sodium/phosphate-cotransporter in myocardial contractile responses to
      inorganic phosphate.
AB  - Na+/Pi-cotransporter utilizes the electrochemical gradient of sodium to transport
      inorganic phosphate (Pi) into the cells of various organs, including heart.
      Because changes in the activity of Na+/Pi-cotransporter may influence the
      concentrations of intracellular Na+, Ca2+ and other ions, the influence of Pi on
      myocardial contractility was investigated. Interaction between Pi and ouabain was
      also investigated. Experiments were performed using isolated perfused rat heart
      under conditions of constant preload (15 mm Hg) and controlled calcium activity
      (0.717 mM). The electronically differentiated value of the left ventricular
      pressure (LVP) signal was used as an index of myocardial contractility. When the
      heart was treated with 2.5 mM Pi, myocardial contractility increased slightly.
      Contractility was increased significantly by treatment with 5 mM Pi. In the
      presence of 10 mM Pi, the heart showed marked but transient increase in
      contractility for the first 15 min of the 60-min treatment period.
      Phosphonoformate (PFA), an inhibitor of Na/Pi-cotransporter, showed selective
      inhibition of Pi-induced increase in myocardial contractility. In another study,
      ouabain and Pi showed additive effect on contractility. The data from these
      studies suggest that myocardial contractile responses to Pi depend on Pi
      concentration and duration of Pi treatment. The data also support the conclusion
      that Na+/Pi-cotransporter may play a role in myocardial contractility.

PMID- 7505368
TI  - Structural and functional myocardial responses to chronic treatment with the Ca2+
      blocker verapamil (Calan-SR) in hypertensive patients.
AB  - We wished to determine whether prolonged therapy with the Ca2+ channel blocker
      verapamil has beneficial structural and functional cardiac effects. Nine
      hypertensive outpatients [systolic blood pressure (SBP) 164 +/- 4 and diastolic
      BP (DBP) 103 +/- 4 mm Hg: men and women, blacks and whites, mean age 48.6 years]
      received 240-480 mg slow-release verapamil (Calan-SR) a day. BP, left ventricle
      (LV) wall thickness and mass, and mitral flow characteristics on
      echocardiography, and plasma catechols and renin were determined at 0, 5, 10, and
      15 months. Patients were compared with 10 normotensive controls, of similar group
      composition (SBP 130 +/- 3 and DBP 82 +/- 1 mm Hg; age 47.2 years). In the
      hypertensive patients, SBP and DBP decreased significantly (p < 0.05), by 14 and
      12 mm Hg, respectively, but remained well above that of controls and > 140/90 mm
      Hg. Diastolic LV septal thickness decreased from 15.3 +/- 0.6 to 14.5 +/- 1.1 mm
      (not significant), while diastolic LV posterior wall thickness (PWTd) decreased
      significantly (p < 0.05) from 15.7 +/- 0.6 to 14.1 +/- 0.7 mm after 8 months, but
      not to the value of the controls. LV diastolic and systolic and left atrial
      dimensions remained constant. Normalized LV mass, initially 60% greater than the
      controls, decreased slightly (11%) but nonsignificantly and remained above that
      of controls. Neither LV mass nor LV posterior wall thinning was correlated with
      reduction in BP. Patient peak systolic wall stress was initially significantly
      lower than that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505369
TI  - Cardiovascular effects and hemodynamic mechanism of action of the novel,
      nonpeptidic renin inhibitor A-74273 in dogs.
AB  - A-74273 is a nonpeptidic, potent inhibitor of human and canine renin (IC50 = 3.1
      and 43 nM, respectively, in plasma at pH 7.4) and has been shown to be orally
      active in dogs. To determine the hemodynamic mechanism underlying this renin
      inhibitor's hypotensive activity, the cardiac and hemodynamic effects of A-74273
      were studied in sodium-depleted and sodium-replete pentobarbital-anesthetized
      dogs. Vehicle [5% dextrose in water (V, D5W), n = 8] or a single dose of A-74273
      was administered intravenously (i.v.) as a bolus followed by a 30-min infusion
      (one tenth the bolus dose per minute). Baseline mean arterial pressure (MAP) was
      similar among all treatment groups, but baseline plasma renin activity (PRA) was
      increased in the sodium-depleted dogs as compared with the sodium-replete dogs.
      In sodium-depleted dogs (n = 7-8/dose), MAP decreased maximally as compared with
      baseline by 4 +/- 1, 19 +/- 3, and 23 +/- 3% during infusion of A-74273 at doses
      of 0.001, 0.01, and 0.1 mg/kg/min, respectively (p < 0.05 vs. baseline or V). The
      two highest infusion doses also produced significant reductions (p < 0.05 vs.
      baseline and V) in systemic vascular resistance (SVR, 21 +/- 2 and 25 +/- 2%) and
      left ventricular end-diastolic pressure (LVEDP, 40 +/- 8 and 47 +/- 12%). In
      sodium-replete dogs (n = 4/dose), an infusion dose of 0.01 mg/kg/min elicited no
      hemodynamic response, whereas 0.1 mg/kg/min reduced MAP by 13 +/- 2% (p < 0.05
      vs. baseline) and SVR by 7 +/- 6%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505370
TI  - Effects of monophosphoryl lipid A on myocardial ischemia/reperfusion injury in
      dogs.
AB  - We wished to determine if the previously observed cardioprotective effects of
      monophosphoryl lipid A (MLA, 65 micrograms/kg intravenously, i.v.), an endotoxin
      derivative, were time related and mediated by an enhancement of antioxidant
      defense mechanisms, i.e., myocardial catalase and superoxide dismutase (SOD)
      activities and neutrophil infiltration as assessed by myeloperoxidase (MPO)
      activity. We also wished to study the effect of pretreatment with MLA on vascular
      endothelial and smooth muscle function in vivo and in vitro. Barbital
      anesthetized dogs were subjected to 60-min left circumflex coronary artery (LCX)
      occlusion followed by 5-h reperfusion. Myocardial catalase, SOD, and MPO
      activities were measured at the end of 5-h reperfusion. Pretreatment with MLA 24
      h before ischemia produced a significant reduction in myocardial infarct size as
      measured by triphenyltetrazolium staining (15.3 +/- 4.4 vs. 30.9 +/- 5.2% in
      controls, p < 0.05), but 1-h pretreatment with MLA had no protective effect. MLA
      pretreatment for 24 h resulted in marked reduction (p < 0.05) in MPO activity in
      the border zone surrounding the infarct. Although a trend indicated an increase
      in catalase activity in the 24-h pretreatment group, no significant changes were
      observed in either catalase or SOD activities among the three groups. The
      cardioprotection produced by MLA was independent of differences in collateral
      blood flow to the ischemic region assessed by radioactive microsphere technique,
      systemic hemodynamics, myocardial oxygen demand, and ischemic bed size. Responses
      of the LCX bed to intracoronary acetylcholine (ACh) or nitroglycerin (NTG) in
      vivo and responses of isolated femoral artery rings to the endothelium-dependent
      vasodilators, ACh, A23187, bradykinin, or the nonendothelium-dependent
      vasodilator, sodium nitroprusside (SNP) in vitro were significantly decreased in
      the MLA 1-h pretreatment group but not in the 24-h pretreatment group. Incubation
      of the femoral artery rings from the MLA 1-h pretreatment group with 3 mM L
      arginine for 1 h reversed the decreased endothelium-dependent responses to ACh
      and A23187, but not those to bradykinin. These results indicate that (a) the MLA
      induced myocardial infarct size reduction was pronounced when MLA was
      administered for 24 h but was not evident at 1-h pretreatment; (b) a decrease in
      neutrophil infiltration into the site of ongoing tissue damage might be partially
      responsible for the protection; (c) vascular endothelial and/or smooth muscle
      function were transiently decreased by MLA administration and returned to nearly
      normal levels 24 h after treatment; and (d) the effect of MLA on endothelium
      dependent responses might be mediated by the L-arginine/nitric oxide (NO)
      pathway.

PMID- 7505371
TI  - Protective effect of serotonin (5-HT2) receptor antagonists in ischemic rat
      hearts.
AB  - Serotonin (5-HT) may play a role in exacerbating thrombosis and coronary spasm
      during myocardial ischemia, but its role in mediating myocardial damage directly
      is not clear. We determined the effect of the 5-HT2 receptor antagonists
      cinanserin (0.1-10 microM), ketanserin (0.3-10 microM), and LY 53857 (1-10
      microM) on time to contracture, recovery of contractile function, and lactate
      dehydrogenase (LDH) release after 25-min global ischemia and 30-min reperfusion
      in isolated rat heart. All 5-HT2 antagonists significantly increased time to
      contracture in a concentration-dependent manner (EC25 = 1.6, 5.5, and 6.1 microM
      for cinanserin, ketanserin, and LY 53857, respectively). These compounds also
      significantly reduced LDH release and improved recovery of contractile function
      during reperfusion. 5-HT > or = 30 microM significantly reduced time to
      contracture, indicating a proischemic effect. The proischemic effect of 5-HT was
      abolished by ketanserin and cinanserin. Inhibition of 5-HT synthesis by
      parachlorophenylalanine resulted in significant cardioprotection, further
      indicating the involvement of 5-HT in the pathogenesis of ischemia in this model.
      Although cinanserin and ketanserin had alpha 1-adrenoceptor blocking effects, LY
      53857 was devoid of this activity at concentrations exhibiting cardioprotection.
      Therefore, 5-HT may exacerbate ischemic injury in rat heart, and this
      exacerbation appears to be mediated specifically by 5-HT2 receptors.

PMID- 7505372
TI  - The evolution of chromosomes. II. Molecular mechanisms.
AB  - It is likely that there was a phase in evolution when the genome consisted of
      unlinked RNA genes, separately replicated. In this paper, we suggest molecular
      mechanisms whereby (i) separate RNA genes could have become linked to form
      chromosomes, (ii) monocistronic transcripts could have been made from these
      chromosomes, and (iii) RNA was replaced by DNA as the genetic material.

PMID- 7505373
TI  - On the plausibility of the clonal expansion theory of the immune system in terms
      of the combinatorial possibilities of amino-acids in antigen and self-tolerance.
AB  - The clonal expansion theory of the immune system was first proposed over 30 years
      age (Jerne, 1955; Burnet, 1959). It still forms the basis of current thinking
      about the immune system. It was not obvious to the authors of this paper that the
      combinatorial possibilities of the 20 available amino acids in antigen peptides
      could result in a system that could distinguish successfully between self and
      foreign antigen, utilizing only the trial and error method proposed by the clonal
      expansion theory. In this paper it is demonstrated that the theory is credible on
      this issue, at least with respect to major histocompatibility complex (MHC)
      restricted antigen recognition, and that the very high proportion of immature
      lymphocytes that die in the thymus is consistent with the theory.

PMID- 7505375
TI  - [It is time to be concerned about problems concerning suffering in severe
      illnesses].

PMID- 7505374
TI  - Lactate dehydrogenase levels during MACOP-B chemotherapy for non-Hodgkin's
      lymphoma.
AB  - Lactate dehydrogenase (LD) levels rose consistently during MACOP-B chemotherapy
      for intermediate and high-grade non-Hodgkin's lymphoma (NHL). Levels peaked at
      week nine and fell to normal within six weeks of completion of therapy. Isoenzyme
      patterns, studied prospectively in seven patients, showed a parallel rise in LD1
      and LD2 suggesting a source other than tumour tissue for the rise in total LD. In
      the absence of evidence of myocardial or renal damage, haematopoietic tissue was
      the most likely source. With no evidence of haemolysis, normal serum levels of
      vitamin B12 and folate and normal red cell folate, dyserythropoiesis was
      considered to be the underlying mechanism. A rising mean corpuscular volume
      further reinforced this suggestion. Intensive use of methotrexate along with co
      trimoxazole as prophylaxis against pneumoycystis carinii is considered the most
      likely cause of marrow dysfunction. Failure to recognise that rising LD levels
      during such therapy is treatment-related, rather than of tumour origin, may lead
      to inappropriate change or abandonment of therapy.

PMID- 7505376
TI  - Free flap survival improved by prostacyclin analogues.
AB  - Free flap transplantations and replantations of extremities are threatened by
      venous occlusion in the postoperative course. In rats, free autogenous groin
      flaps were transplanted to the neck using microsurgical techniques. On the first
      postoperative day, the draining vein of the flap was temporarily clamped. In the
      control group there was always a total loss of the flaps by haemorrhagic
      necrosis. The intraarterial flap perfusion by iloprost during the clamping was
      able to diminish the ischaemic effects; 80% of the flaps survived. The systemic
      application of iloprost by intravenous infusion reduced the ischaemic effects in
      a similar way. Serious complications such as intraabdominal bleeding or bleeding
      in the donor area were seen after intravenous administration. Cicaprost had a
      similar protective effect on flap ischaemia after intravenous infusion. Flap
      survival was comparable to iloprost. Severe complications seemed to be less.
      Prostacyclin analogues were able to diminish damage of secondary ischaemia caused
      by venous occlusion.

PMID- 7505377
TI  - Isolation and comparison of nucleic acids from land plants: nuclear and
      organellar genes.

PMID- 7505379
TI  - Direct ribosomal RNA sequencing for phylogenetic studies.

PMID- 7505378
TI  - Molecular approaches to mammalian retrotransposon isolation.

PMID- 7505380
TI  - Comparison of nucleic acids from microorganisms: sequencing approaches.

PMID- 7505381
TI  - Collection and storage of vertebrate samples.

PMID- 7505382
TI  - Analysis of DNA sequence data: phylogenetic inference.

PMID- 7505383
TI  - Experimental approaches for detecting self-splicing group I introns.

PMID- 7505384
TI  - Experimental testing of theories of an early RNA world.

PMID- 7505385
TI  - Classification of Italian isolates of Borrelia burgdorferi into three genomic
      groups.
AB  - In this study we investigated the genotypic characteristics of some locally
      isolated strains of B. burgdorferi by three different methodologies: restriction
      endonuclease analysis (REA), Southern blot hybridization with whole DNAs from
      Borrelia strains and Southern blot hybridization with rRNA 16 + 23S genes derived
      from E. coli. REA fingerprintings were evaluated by cluster analysis, according
      to the principles of numerical taxonomy. The genomas of the locally isolated
      strains were compared with borreliae originating from different countries of
      Europe, including Sweden and with the American reference strain B31. Among the
      European strains, some already described by Baranton (Baranton et al., 1992) as
      representatives of different genomic groups Borrelia sensu stricto and Borrelia
      garinii were used. By the different techniques the isolates were included in
      three genomic groups which could correspond to the three genospecies identified
      by Baranton, namely B. burgdorferi sensu stricto, B. garinii and B. group VS461:
      in fact two strains were included in a homogeneous group, probably corresponding
      to the VS461 genomic group, together with other European borreliae; one isolate
      was included in a group consisting of B31 and some other European strains already
      described as belonging to Borrelia burgdorferi in sensu stricto. Finally two
      isolates were ascribed to a third genomic group probably corresponding to the
      genospecies indicated as Borrelia garinii. These findings indicate that a small
      number of Borrelia strains isolated from a very restricted area can be
      genetically heterogeneous.

PMID- 7505386
TI  - [Prevalence of HBV surface antigens, anti-HBD and anti-HCV antibodies in patients
      with virus-related chronic liver disease].
AB  - In the present study, we investigated Hepatitis B virus (HBV), Hepatitis C virus
      (HCV), and Hepatitis D virus (HDV) status in patients with chronic liver diseases
      seen in the period of 1990-1992 using enzyme-linked immunosorbent assay (ELISA)
      kits. There were 126 male and 64 female patients with a mean age of 42.3 years
      (range 17-70). Of the 198 patients, 68 (35.7%) had evidence of HCV infection. One
      hundred and twenty-three patients (64.7%) were positive for hepatitis B surface
      antigen (HBsAg). Of the 123 HBsA positive patients, 35 (28.4%) were positive for
      Anti-HDV. Fourteen patients were negative for markers of both HCV and HBV. Liver
      histology showed persistent hepatitis in 31 patients (16.3%), chronic active
      hepatitis in 77 (40.6%). Cirrhosis was diagnosed in 82 patients (43.1%). Our
      results indicate that HCV infection plays a role in chronic liver disease
      especially where the etiology appears obscure.

PMID- 7505387
TI  - [Hepatitis markers in hemodialysis patients].
AB  - In this study, antibodies against blood-borne hepatitis viruses (Hepatitis B, C
      and D) were investigated by ELISA in 43 patients with chronic renal
      insufficiency, at Hemodialysis Unit of Ondokuz Mayis University, Faculty of
      Medicine. 32 (76.2%) of the patients were found positive Anti-HBc total antibody
      and 12 (27.5%) patients were HBsAg carriers. 14 (32.5%) patients had Anti-HBs
      which showed protective immunity. Anti-HBs antibody was found negative in 6
      patients after Hepatitis B infection. 9 (75%) of the HBsAg carriers had Anti
      Delta antibody. 34 (79.1%) patients showed Anti-HCV positivity, 6 (18.2%) of HCV
      seropositive patients were found to be positive for HBsAg. There wasn't any
      correlation between length of time on hemodialysis, age and seropositivity of
      hepatitis markers. A correlation was detected between multiple transfusion and
      Anti-HCV seropositivity. The prevalence of HBsAg, Anti-HBc total and Anti-HCV
      were sequentially found 6%, 38%, 1% among healthy blood donors taken as a control
      group. Hepatitis virus infection was frequently seen in hemodialysis patients
      because of multiple blood transfusion. Chronicity is high because of
      insufficiency of cellular and humoral immunity. Testing blood for hepatitis
      viruses markers before blood transfusion and Hepatitis B vaccination programme
      might control viral hepatitis infection in hemodialysis units.

PMID- 7505388
TI  - The GEF1 gene of Saccharomyces cerevisiae encodes an integral membrane protein;
      mutations in which have effects on respiration and iron-limited growth.
AB  - We have isolated a new class of respiration-defective, i.e petite, mutants of the
      yeast Saccharomyces cerevisiae. Mutations in the GEF1 gene cause cells to grow
      slowly on rich media containing carbon sources utilized by respiration. This
      phenotype is suppressed by adding high concentrations of iron to the growth
      medium. Gef1- mutants also fail to grow on a fermentable carbon source, glucose,
      when iron is reduced to low concentrations in the medium, suggesting that the
      GEF1 gene is required for efficient metabolism of iron during growth on
      fermentable as well as respired carbon sources. However, activity of the iron
      uptake system appears to be unaffected in gef1- mutants. Fe(II) transporter
      activity and regulation is normal in gef1- mutants. Fe(III) reductase induction
      during iron-limited growth is disrupted, but this appears to be a secondary
      effect of growth rate alterations. The wild-type GEF1 gene was cloned and
      sequenced; it encodes a protein of 779 amino acids, 13 possible transmembrane
      domains, and significant similarity to chloride channel proteins from fish and
      mammals, suggesting that GEF1 encodes an integral membrane protein. A gef1-
      deletion mutation generated in vitro and introduced into wild-type haploid
      strains by gene transplacement was not lethal. Oxygen consumption by intact gef1-
      cells and by mitochondrial fractions isolated from gef1- mutants was reduced 25
      50% relative to wild type, indicating that mitochondrial function is defective in
      these mutants. We suggest that GEF1 encodes a transport protein that is involved
      in intracellular iron metabolism.

PMID- 7505390
TI  - Nuclear localization of bacterial Streptoalloteichus hindustanus bleomycin
      resistance protein in mammalian cells.
AB  - Prokaryotes produce a variety of toxins that affect genomic function of both
      eukaryotes and prokaryotes. The 375-base pair bacterial gene Streptoalloteichus
      hindustanus (Sh) ble encodes a small protein, Streptoalloteichus hindustanus
      bleomycin resistance protein (BRP), that inhibits in vitro DNA cleavage by the
      prokaryotic glycopeptide bleomycin, which is a clinically used anticancer drug.
      NIH/3T3 cells infected with a retroviral vector containing Sh ble (SH-9 cells)
      were highly resistant to the cytotoxicity of bleomycin-like drugs but not to the
      cytotoxicity of other, structurally unrelated, DNA-cleaving agents. Expression of
      BRP did not markedly alter total cellular content or distribution of bleomycin
      like compounds. Fluorescently labeled bleomycin was primarily localized in
      cytoplasmic vesicles in NIH/3T3 and SH-9 cells, whereas BRP, which has no
      established nuclear localization sequence, was segregated to the nucleus and more
      specifically to euchromatin. This karyophilic BRP may intercept bleomycin in the
      nucleus.

PMID- 7505389
TI  - VirR and Mry are homologous trans-acting regulators of M protein and C5a
      peptidase expression in group A streptococci.
AB  - Transcription of the group A streptococcal M12 protein gene (emm12) and the C5a
      peptidase gene (scpA), which encodes an inhibitor of complement-mediated
      chemotaxis, was previously shown to depend on a third genetic locus, designated
      virR. A 1.6 kb region of DNA which is 200 bp upstream of emm12 and is thought to
      contain the virR locus, was sequenced. An open reading frame which overlaps
      deletion mutations that define virR was identified. The sequence of the encoded
      VirR protein, which was deduced to contain 499 amino acids, is characteristic of
      cytoplasmic proteins. Comparison of the VirR protein to a variety of DNA binding
      proteins, such as lambda Cro, revealed a DNA binding motif. VirR was also
      compared to the M6 positive regulator, mry, and found to be 98% homologous. The
      predicted virR promoter is preceded by two sets of inverted repeats, in contrast
      to mry which is preceded by one repeat. Introduction of virR on the shuttle
      vector pAM401 into a strain of group A Streptococcus with a deletion in the
      chromosomal virR gene demonstrated that the VirR protein activated transcription
      of both emm12 and scpA genes in trans. Analysis of RNA by Northern blot using
      virR-specific probes identified two virR transcripts, a 1.6 kb transcript which
      corresponds to the predicted size of the gene, and a second transcript, 3.5 kb,
      which also overlaps virR. These results demonstrate that virR and mry are
      structurally and functionally very similar and show that the former is a trans
      activator of both M protein and C5a peptidase synthesis.

PMID- 7505391
TI  - Stable association of pp60src and pp59fyn with the focal adhesion-associated
      protein tyrosine kinase, pp125FAK.
AB  - Changes in cellular growth and dramatic alterations in cell morphology and
      adhesion are common features of cells transformed by oncogenic protein tyrosine
      kinases, such as pp60src and other members of the Src family. In this report, we
      present evidence for the stable association of two Src family kinases (pp60src
      and pp59fyn) with tyrosine-phosphorylated forms of a focal adhesion-associated
      protein tyrosine kinase, pp125FAK. In Src-transformed chicken embryo cells, most
      of the pp125FAK was stably complexed with activated pp60src (e.g., pp60(527F).
      The stable association of pp125FAK with pp60(527F) in vivo required the
      structural integrity of the Src SH2 domain. The association of pp60(527F) and
      pp125FAK could be reconstituted in vitro by incubation of normal cell extracts
      with glutathione S-transferase fusion proteins containing SH2 or SH3/SH2 domains
      of pp60src. Furthermore, the association of isolated SH2 or SH3/SH2 domains with
      in vitro 32P-labeled pp125FAK protected the major site of pp125FAK
      autophosphorylation from digestion with a tyrosine phosphatase, indicating that
      the autophosphorylation site of pp125FAK participates in binding with Src.
      Immunoprecipitation of Src family kinases from extracts of normal chicken embryo
      cells revealed stable complexes of pp59fyn and tyrosine-phosphorylated pp125FAK.
      These data provide evidence for a direct interaction between two cytoplasmic
      nonreceptor protein tyrosine kinases and suggest that Src may contribute to
      changes in pp125FAK regulation in transformed cells. Furthermore, pp125FAK may
      directly participate in the targeting of pp59fyn or possibly other Src family
      kinases to focal adhesions in normal cells.

PMID- 7505393
TI  - Characterization of somatostatin transactivating factor-1, a novel homeobox
      factor that stimulates somatostatin expression in pancreatic islet cells.
AB  - The endocrine pancreas consists of several differentiated cell types that are
      distinguished by their selective expression of peptide hormones such as insulin,
      glucagon, and somatostatin. Although a number of homeobox-type factors have been
      proposed as key regulators of individual peptide genes in the pancreas, their
      cellular distribution and relative abundance remain uncharacterized. Also, their
      overlapping DNA binding specificities have further obscured the regulatory
      functions these factors perform during development. In this report we
      characterize a novel homeobox-type somatostatin transactivating factor termed STF
      1, which is uniformly expressed in cells of the endocrine pancreas and small
      intestine. The 283-amino acid STF-1 protein binds to tissue-specific elements
      within the somatostatin promoter and stimulates somatostatin gene expression both
      in vivo and in vitro. Remarkably, STF-1 comprises the predominant tissue-specific
      element-binding activity in nuclear extracts from somatostatin-producing
      pancreatic islet cells, suggesting that this protein may have a primary role in
      regulating peptide hormone expression and specifying endocrine cell lineage in
      the developing gut.

PMID- 7505392
TI  - Functional expression of P-glycoprotein in Saccharomyces cerevisiae confers
      cellular resistance to the immunosuppressive and antifungal agent FK520.
AB  - We have recently reported that expression in yeast cells of P-glycoprotein (P-gp)
      encoded by the mouse multidrug resistance mdr3 gene (Mdr3) can complement a null
      ste6 mutation (M. Raymond, P. Gros, M. Whiteway, and D. Y. Thomas, Science
      256:232-234, 1992). Here we show that Mdr3 behaves as a fully functional drug
      transporter in this heterologous expression system. Photolabelling experiments
      indicate that Mdr3 synthesized in yeast cells binds the drug analog
      [125I]iodoaryl azidoprazosin, this binding being competed for by vinblastine and
      tetraphenylphosphonium bromide, two known multidrug resistance drugs.
      Spheroplasts expressing wild-type Mdr3 (Ser-939) exhibit an ATP-dependent and
      verapamil-sensitive decreased accumulation of [3H]vinblastine as compared with
      spheroplasts expressing a mutant form of Mdr3 with impaired transport activity
      (Phe-939). Expression of Mdr3 in yeast cells can confer resistance to growth
      inhibition by the antifungal and immunosuppressive agent FK520, suggesting that
      this compound is a substrate for P-gp in yeast cells. Replacement of Ser-939 in
      Mdr3 by a series of amino acid substitutions is shown to modulate both the level
      of cellular resistance to FK520 and the mating efficiency of yeast mdr3
      transformants. The effects of these mutations on the function of Mdr3 in yeast
      cells are similar to those observed in mammalian cells with respect to drug
      resistance and transport, indicating that transport of a-factor and FK520 in
      yeast cells is mechanistically similar to drug transport in mammalian cells. The
      ability of P-gp to confer cellular resistance to FK520 in yeast cells establishes
      a dominant phenotype that can be assayed for the positive selection of intragenic
      revertants of P-gp inactive mutants, an important tool for the structure-function
      analysis of mammalian P-gp in yeast cells.

PMID- 7505394
TI  - Hormonal regulation of pp60c-src expression during osteoclast formation in vitro.
AB  - Recent studies have shown that the protooncogene c-src is required for normal
      osteoclastic bone resorption. In this study we examined the expression and
      regulation of pp60c-src in murine bone marrow cultures in which bone-resorbing
      multinucleated osteoclasts form over 6 days of culture. We found that both pp60c
      src protein expression and pp60c-src tyrosine kinase activity correlated closely
      with the numbers of active osteoclasts in the cultures. PTH increased the numbers
      of osteoclasts, pp60c-src tyrosine kinase activity, and src protein, whereas
      calcitonin decreased the numbers of osteoclasts, src protein, and tyrosine kinase
      activity. However, when calcitonin was incubated for short periods (< 2 h) with
      the active osteoclasts present after 6 days of culture, there was a decrease in
      pp60c-src tyrosine kinase activity and the phosphorylation state, but not in
      total pp60c-src protein. These data suggest that pp60c-src is expressed in
      cultures of osteoclasts in parallel with the number of active bone-resorbing
      osteoclasts. They indicate that pp60c-src activity in osteoclast cultures depends
      on the activity and numbers of osteoclasts and is hormone regulated. As
      calcitonin receptors are detectable only in osteoclasts in these cultures, the
      inhibitory effects of calcitonin suggest that the critical site for pp60c-src
      expression in these cultures is in osteoclasts.

PMID- 7505395
TI  - Differential DNA methylation of the chorionic gonadotropin beta-subunit multigene
      family.
AB  - In addition to its synthesis in the developing placenta, human CG or the isolated
      alpha- and beta-subunits are synthesized by a wide variety of both trophoblastic
      and nontrophoblastic tumor cell lines. The beta-subunit confers unique biological
      activity on the hormone and is encoded by a family of six genes or pseudogenes
      linked physically with beta LH at one locus on chromosome 19. Previous work has
      demonstrated that members of the beta CG family are not expressed to the same
      extent in first-trimester placenta. The factors allowing differential expression
      of the six nearly identical genes are unknown. It is also undetermined which of
      the multiple beta CG genes are actively expressed in the tumor cell lines that
      produce beta-subunit ectopically. One potential mechanism for control of beta CG
      gene expression is DNA methylation. A unique method of two-dimensional DNA
      electrophoresis was used to analyze the methylation status of each of the
      individual beta CG genes in placenta and in tumor cell lines that either do or do
      not express the protein. The DNA from each source exhibited unique, reproducible
      methylation patterns over the six beta CG genes. Particularly interesting were
      the observations that: 1) despite their nearly identical sequences and close
      chromosomal proximity, the six beta CG genes are distinguished from one another
      within the same and different cell types by their extent and pattern of
      methylation; 2) the beta CG locus is significantly hypomethylated in placenta, a
      state maintained in choriocarcinoma cells (JAr); 3) the beta CG gene cluster is
      unmethylated at a limited set of sites in DNA from both 2RA (a transformed
      fibroblast cell line that does not produce beta-subunit) and CBT (a glioblastoma
      cell line that produces beta-subunit ectopically), suggesting that general
      demethylation of the domain does not accompany activation of the locus in CBT but
      rather that site-specific changes may be responsible, at least in part, for
      inappropriate beta CG expression; and 4) the ratio of beta CG gene 3 transcripts
      to beta CG gene 5 transcripts is at least 10-fold higher in CBT cells than in JAr
      cells, suggesting that the reduced methylation in CBT cells of gene 3 compared to
      gene 5 may be a factor contributing to the activity of these genes.

PMID- 7505396
TI  - [Immunological principles of polysaccharide-protein conjugate vaccination].
AB  - Haemophilus influenzae and Streptococcus pneumoniae are bacteria with a
      polysaccharide capsule. The production of specific antibodies against capsular
      polysaccharide plays a pivotal role in the defence against these organisms.
      However, children under the age of two years do not at all or only poorly respond
      to an infection with encapsulated bacteria or after vaccination with purified
      capsular polysaccharide antigen. In contrast, protein antigens, e.g. tetanus- and
      diphtheriae-toxoid, are good immunogens in this age group. The difference between
      polysaccharide antigen and protein antigen is that the former are T-dependent
      antigens whereas the latter are T-independent. The reason for this age dependent
      "immunodeficiency" is not clear. A functional immaturity of a B-cell population
      seems to be the reason for the unresponsiveness of young children against Ti-2
      antigens. The Haemophilus conjugate vaccine contains the capsular polysaccharide
      chemically conjugated to a carrier protein. This results in an immune response
      against the polysaccharide with characteristics of a T dependent antigen, giving
      high immunogenicity even in children under the age of two years, resulting in
      high antibody-production and the induction of immunological memory.

PMID- 7505397
TI  - [Physical and mental development of children with congenital hypothyroidism].
AB  - 69 children with congenital hypothyroidism, who were detected by neonatal
      screening in Lower Saxony, were reevaluated 1-12 years after diagnosis. They had
      been treated either by regional children's hospitals, local pediatricians or
      general practitioners. Substitution of thyroid hormone had started for the
      majority between day 7 and 14, for 17%, however, only later. Symptoms suggestive
      of hypothyroidism at birth were observed in 35 children, but only 3 cases were
      correctly diagnosed before the result of the screening was known. Further
      diagnostic tests to elucidate the cause of congenital hypothyroidism had been
      performed in 33 children. In 36 cases the etiology remained undiagnosed at the
      evaluation. Hormone therapy had been administered continuously in all cases. The
      somatic development of all children was normal. Bone age at the time of diagnosis
      was retarded in more than 50%, later it became normal in most cases. The
      psychomotor and intellectual development was satisfactory as assessed by
      psychometric tests. The mean value of the Intelligence Quotients in the children
      older than six years was 96.3. 5 children of this age group had an IQ below 85
      and only one child had an IQ of more than 115. In the younger group the results
      were similar, but children younger than 4 years showed deficiencies in speech
      development. In summary, the somatic development of the re-examined children with
      congenital hypothyroidism was normal, but the psychomotor and intellectual
      development was only subnormal in some cases. It is therefore suggested that
      children with congenital hypothyroidism should be closely followed by experienced
      pediatricians, especially in the early years of life.

PMID- 7505398
TI  - Human glioblastoma cells produce granulocyte-macrophage colony-stimulating factor
      in vitro, but not in vivo, without expressing its receptor.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) production and receptor
      expression by human glioblastomas was studied. Enzyme-linked immunosorbent assay
      showed four of 10 glioblastoma cell lines spontaneously released GM-CSF (2.9-9.2
      pg GM-CSF protein/ml culture medium), which was enhanced by stimulation with
      tumor necrosis factor-alpha (TNF) (10 U/ml) up to 410 pg/ml. TNF also induced
      secretion of GM-CSF by another cell line. Northern blot analysis identified
      increasing GM-CSF gene expression by cells following TNF stimulation. However, no
      GM-CSF protein was detectable in the cerebrospinal fluid of three malignant
      glioma patients. Intratumoral administration of TNF in the patients also failed
      to stimulate GM-CSF levels in the cerebrospinal fluid. A binding assay using flow
      cytometry with biotinylated GM-CSF and Scatchard analysis using 125I-labeled GM
      CSF failed to demonstrate GM-CSF receptor expression on the 13 cell lines.
      Exogenous GM-CSF stimulation had no effect on production of prostaglandin E2,
      interleukin-6, or interleukin-8 by glioma cells. Human glioblastoma cells secrete
      GM-CSF without expressing the receptor in vitro, but there was no evidence of GM
      CSF production in vivo.

PMID- 7505400
TI  - Effects of decompressive craniectomy on regional cerebral blood flow in severe
      head trauma patients.
AB  - The effect of decompressive craniectomy on regional cerebral blood flow (rCBF)
      was investigated in five patients with severe head trauma who underwent
      decompressive craniectomy. Repeated rCBF studies using single photon emission
      computed tomography with 99mtechnetium-hexamethylpropyleneamine oxime observed
      that a hyperperfusion area (focal CBF increase) occurred in the decompressed
      brain within 24 hours after decompressive craniectomy. The hyperperfusion area in
      the decompressed brain enlarged and increased in severity by 1 week after
      surgery. However, it attenuated and disappeared by 1 month after surgery. The
      chronology of the hyperperfusion area corresponded to the change in the swelling
      of decompressed brain observed by x-ray computed tomography. Patient
      consciousness showed a significant and progressive improvement in the
      postoperative 1 month period. Decompressive craniectomy may cause a focal CBF
      increase in the decompressed brain related to the beneficial effect in patients
      with acute severe head trauma.

PMID- 7505399
TI  - Experimental radioimmunotherapy of a xenografted human glioma using 131I-labeled
      monoclonal antibody to epidermal growth factor receptor.
AB  - 131I-labeled F(ab')2 fragments of murine monoclonal antibody (MAb) 425 specific
      to the epidermal growth factor receptor expressed on human gliomas were used in
      experimental human malignant glioma immunotherapy. Two injections of 150 microCi
      131I-labeled 425 F(ab')2 achieved growth inhibition of U-87MG human malignant
      glioma xenografts in nude mice. This radiolabeled specific MAb F(ab')2 was
      significantly superior to radiolabeled fragments of an anti-hepatitis virus
      control MAb A5C3 in influencing tumor growth. However, similar treatment of
      established human malignant glioma xenografts did not inhibit progressive tumor
      growth significantly. No clear tumor inhibition was produced by unlabeled MAb 425
      F(ab')2. These studies suggest that 131I-labeled MAbs have a significant
      antitumor effect where unmodified antibody is ineffective. Multiple doses of
      antibody may achieve an increase in labeled MAb concentration in tumors.

PMID- 7505401
TI  - Long-term follow-up study of "epileptic type" moyamoya disease in children.
AB  - Twenty-three patients with epileptic type moyamoya disease are reviewed among 200
      moyamoya disease patients. Ten boys and 13 girls aged 5 months to 12 years were
      followed over 6 months to 17.3 years. Six had generalized seizure and 17 had
      focal seizure. Operations were performed within 1 year in eight patients, within
      1-3 years in five, and more than 3 years after onset in 10. Nineteen patients
      improved and suffered no seizure without receiving antiepileptic drugs, but four
      patients developed true epilepsy and three of these suffered cerebral infarction.
      Multivariate analyses showed that toddlers aged less than 1 year and mild or
      severe abnormal computed tomographic (CT) findings correlated with a bad outcome.
      This study showed that epileptic type moyamoya disease has the same clinical
      features as transient ischemic attack or infarction type. Age under 1 year and CT
      abnormalities indicate a poor prognosis and necessity for early reconstructive
      surgery.

PMID- 7505402
TI  - Gross total removal of adult brainstem glioma--two case reports.
AB  - Two adult patients with brainstem glioma were successfully treated surgically. A
      37-year-old male had a dorsally exophytic pontine glioma developing from the
      fourth ventricular fundus, and another 27-year-old male an intrinsic nodular
      mesencephalic glioma. Preoperative magnetic resonance imaging clearly visualized
      the tumor margin in both cases, and showed the relationship between the tumor and
      brainstem structure accurately. The tumors were radically excised using
      intraoperative evoked potential monitoring, ultrasonic surgical aspirator, and
      microsurgical techniques. Surgery is indicated when the tumor margin in the
      brainstem and adjacent region is clear, and the approach is possible without
      affecting the functional prognosis.

PMID- 7505403
TI  - Solitary pyogenic thalamic abscess--two case reports.
AB  - We report two patients with solitary thalamic abscesses, occurring among 91
      consecutive patients (2.2%) with computed tomography (CT)-diagnosed and
      surgically-verified brain abscess experienced in our college during 1975 to 1991.
      A 9-year-old girl with congenital heart disease experienced frequent vomiting
      followed by left hemiparesis and deterioration of consciousness. CT demonstrated
      a right thalamic ring-enhanced lesion. Purulent material was aspirated via a burr
      hole. She died of heart failure on the 5th postoperative day. Autopsy disclosed
      diffuse brain swelling and an encapsulated abscess in the right thalamus, which
      had ruptured into the third ventricle. A 30-year-old female experienced headache,
      nausea, and vomiting, which progressed to somnolence and right hemiparesis. CT
      demonstrated a left thalamic ring-enhanced lesion. Purulent material was
      aspirated by stereotactic procedures. All symptoms had resolved by the end of the
      2nd postoperative week.

PMID- 7505404
TI  - Dissecting aneurysm of the posterior inferior cerebellar artery--case report.
AB  - A 29-year-old male presented with a dissecting aneurysm of the left posterior
      inferior cerebellar artery manifesting as left lateral medullary syndrome due to
      brainstem ischemia. Extirpation of the aneurysm and anastomosis of the occipital
      artery to the posterior inferior cerebellar artery were performed simultaneously.
      The dissecting aneurysm was confirmed by histological examination of the surgical
      specimen.

PMID- 7505405
TI  - Chronic encapsulated intracerebral hematoma associated with angiographically
      occult arteriovenous malformation--case report.
AB  - A 34-year-old female presented with a rare chronic encapsulated intracerebral
      hematoma associated with an angiographically occult arteriovenous malformation. A
      neovascularized fibrous capsule containing various stages of intracerebral
      hematoma formation was removed. These unusual entities mimic brain tumors or
      abscesses because of gradual growth and slowly progressive neurological deficits.
      Repeated bleeding or exudation from the capillaries of the capsule may allow
      expansion of the chronic encapsulated intracerebral hematoma.

PMID- 7505406
TI  - Pituitary adenoma combined with Rathke's cleft cyst--case report.
AB  - A rare pituitary adenoma associated with Rathke's cleft cyst was discovered
      incidentally in a 44-year-old male admitted after head trauma. Neurological and
      physiological examination found no abnormalities, except for panhypopituitarism.
      Computed tomography and magnetic resonance imaging demonstrated a solid mass in
      the sellar cavity with suprasellar extension, associated with a cystic mass
      extending into the third ventricle. The tumor was removed subtotally by the
      transcranial approach. Light microscopy demonstrated that the cyst wall was
      composed of ciliated columnar cells, cuboidal cells, and goblet cells, and the
      solid part indicated chromophobe pituitary adenoma. Immunohistochemistry
      demonstrated that a few adenoma cells were positive for prolactin and the cyst
      wall cells were positive for cytokeratin and negative for S-100 protein.

PMID- 7505407
TI  - Meningioangiomatosis not associated with von Recklinghausen's disease--case
      report.
AB  - A 7-year-old girl with meningioangiomatosis not associated with von
      Recklinghausen's disease is described. The radiological findings were similar to
      meningioma, but intraoperatively, a thin septum was found between the mass and
      the dura mater. Microscopically, there was significant proliferation of
      fibroblastic spindle-shaped cells and collagenous fibers in the subarachnoid
      space. Proliferated cells had penetrated into the cortical tissue along the
      irregularly branched blood vessels. Immunohistochemically, these penetrating
      perivascular cells were negative for glial fibrillary acidic protein and S-100
      protein, and positive for vimentin staining. These findings suggest that the
      histogenesis of the spindle-shaped cells is most probably meningothelial.

PMID- 7505408
TI  - Expression of neuroendocrine secretory protein 7B2 mRNA in the mouse and rat
      pituitary gland.
AB  - The secretory polypeptide 7B2 is produced in different endocrine and
      neuroendocrine cells, where it is presumed to play a role in the hormone
      secretion mechanism. In this study, we examined a pattern of 7B2 mRNA expression
      in the mouse and rat pituitary gland. When [35S]-labeled antisense cRNA probes
      were used for in situ hybridization, 7B2 mRNA transcripts were detected within
      virtually all endocrine cells of the anterior lobe (gonadotrophs, thyrotrophs,
      corticotrophs, somatotrophs and lactotrophs) and of the intermediate lobe
      (melanotrophs). The posterior lobe was negative. By immunocytochemistry, 7B2
      accumulation was observed within melanotrophs in the intermediate lobe and within
      gonadotrophs and thyrotrophs in the anterior lobe. The question of 7B2 production
      in other pituitary cells, such as corticotrophs, somatotrophs and lactotrophs,
      was studied under culture conditions. The corticotroph AtT-20 and somatrotroph
      GH3 cell lines both expressed 7B2 mRNA and contained 7B2 protein detectable by
      radioimmunoassay. However, this protein could not be visualized by
      immunocytochemistry. Thus, it is possible that 7B2 is produced in all hormone
      synthesizing cells of the pituitary gland, being stored only within some of them
      and rapidly exported after synthesis from others.

PMID- 7505409
TI  - Spinal cord transection in adult rats: effects of local infusion of nerve growth
      factor on the corticospinal tract axons.
AB  - The spinal cord of adult female rats was completely transected at the T8 level.
      Nerve growth factor (NGF) was administered at the lesion site via indwelling,
      implanted, osmotic minipumps. Purified NGF was supplied at doses of 100, 200, and
      500 micrograms during a 30-day period. Control rats were treated with saline. At
      the end of the treatment, the proximal stump of corticospinal tract axons in the
      spinal cord was labeled with anterograde transported horseradish peroxidase (HRP)
      injected into the sensorimotor cortex. In control rats, the corticospinal tract
      axons ended abruptly, proximal to the zone of maximal damage. Sterile swellings
      developed at the axon tips, and no labeled axonal sprouts were apparent. On the
      contrary, in NGF-treated animals, the leading front of the corticospinal tract
      axons showed a trend of approaching the zone of maximal damage following abnormal
      paths through the dorsal-injured white matter. Axonal sprouts were seen more
      proximally, traveling toward the transection site in aberrantly located dorsal
      paths, completely outside the normal position of the corticospinal tract. NGF
      seems to partly restore the pattern of the regenerative behavior of the severed
      corticospinal tract axons after spinal cord transection in newborn rats, i.e.,
      the induction of axonal sprouting in aberrantly located dorsal paths. An
      automated image analysis of the HRP reaction field close to the transection site
      demonstrated that the density of HRP-labeled axons in the corticospinal tract was
      significantly higher in the NGF-treated rats than in the control rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7505410
TI  - Alterations in the concentration of serotonergic and dopaminergic substances in
      the cerebrospinal fluid of patients with Parkinson's disease, and their changes
      after L-dopa administration.
AB  - In untreated patients with Parkinson's disease (PD), the total (free and
      conjugated) serotonin (5-HT) and dopamine (DA) concentrations in the
      cerebrospinal fluid decreased significantly. While the 5-HT concentration
      displayed a non-significant trend of negative correlation with the DA
      concentration in controls, it had a significant positive correlation with the DA
      concentration in untreated PD patients. In L-dopa-treated patients, the DA
      concentration increased remarkably, whereas the 5-HT concentration decreased
      further compared with untreated patients. The tryptophan, 5-hydroxyindolacetic
      acid (5-HIAA), and 3-OH kynurenine concentrations had significant positive
      correlations with L-dopa doses. The 5-HT concentration had a significant positive
      correlation with scores of psychomatric testing in L-dopa-treated patients.

PMID- 7505411
TI  - Observation of Merkel cells with scanning electron microscopy.
AB  - This paper first elucidated the overall morphology of Merkel cells in the rat
      touch dome with scanning electron microscopy (SEM). Quinacrine-fluorescent Merkel
      cells in the touch dome were exposed by enzymatic treatment following application
      of dithiothreitol, photographed and then fixed. By referring to the photograph,
      the same fluorescent cells were easily identified under the SEM. Enzymatically
      isolated Merkel cells were also examined with SEM. Unlike quinacrine negative,
      ordinary epidermal cells, the Merkel cells had numerous finger-like processes,
      ranging from 0.1 to 0.25 micron in diameter and attaining to 2.5 microns in
      length.

PMID- 7505412
TI  - Hyperthermia induces 72kDa heat shock protein expression in rat brain in non
      neuronal cells.
AB  - The distribution of the nonconstitutive 72 kDa heat shock protein (HSP) in the
      brains of rats 24 h following graded periods of hyperthermia was studied
      immunocytochemically. Hyperthermia induced HSP-72 diffusely in cells throughout
      the cortex, hippocampus and basal ganglia in a dose dependent manner. The cell
      morphology and location in white matter appeared non-neuronal. Following
      ischemia, neuronal HSP expression was prominent. These data raise questions
      regarding prior reports of hyperthermic induction of neuronal HSP expression and
      the potential pathogenesis of prior hyperthermia in protection against subsequent
      neuronal injury from ischemia.

PMID- 7505413
TI  - Central administration of senktide, a tachykinin NK-3 agonist, has an
      antidiuretic action by stimulating AVP release in water-loaded rats.
AB  - Intracerebroventricular (i.c.v.) injections of senktide (0.01-10 nmol), a
      tachykinin NK-3 agonist, had an antidiuretic action in water-loaded rats (4.5%
      body wt.). Pretreatment with OPC-31260 (1 mg/kg, i.v.), a non-peptide vasopressin
      V2 antagonist, inhibited the antidiuretic action induced by exogenous arginine
      vasopressin (AVP, 0.1 micrograms/kg, i.v.) and senktide (0.1 nmol, i.c.v.). In
      addition, senktide (11.8 nmol, i.c.v.) caused a marked increase of the plasma AVP
      level in conscious rats. These results suggest that the central NKB analogue
      senktide has an antidiuretic effect by stimulating AVP secretion from the
      pituitary gland through the NK-3 receptor in the hypothalamus.

PMID- 7505414
TI  - Differential spinal projections of subregions in the forelimb area of the motor
      cortex in the cat.
AB  - Anterograde transport of wheat germ agglutinin conjugated to horseradish
      peroxidase (WGA-HRP) was used to examine the topography of projections from the
      forelimb area of motor cortex to the cervical spinal cord in the cat. Tracer was
      injected in sites in the rostrolateral (RL-MCx) and caudolateral (CL-MCx)
      subregions concerned with the distal forelimb. Whereas both subregions projected
      throughout the cervical cord, with the greatest density of label present in the
      cervical enlargement, the dorso-ventral distributions were different for the two
      injection sites. Injections in RL-MCx produced labeling in the lateral portions
      of laminae VI, VII, and VIII in the upper cervical segments. This corresponds to
      the locations of propriospinal neurons that project to forelimb motor nuclei used
      in reaching [Exp. Brain Res., 42 (1981) 299-318]. In the cervical enlargement,
      labeling was present in laminae V, VI, VII, and part of VIII. At all levels
      examined, the density of labeling was greatest in the intermediate zone. After CL
      MCx injection, labeling was concentrated in the dorsal horn both in the upper
      cervical segments and in the cervical enlargement. These findings suggest that
      the two motor cortical subregions project to different propriospinal and
      interneuronal systems in the cervical cord and support the idea that the two
      subregions play different roles in controlling forelimb movements.

PMID- 7505415
TI  - Neurons in the intertrigeminal region of the rat send projection fibers to the
      superior colliculus.
AB  - A retrograde WGA-HRP and anterograde PHA-L study in the rat indicated that many
      neurons in the intertrigeminal region (ITR) sent their axons to the superior
      colliculus (SC), bilaterally with a clear-cut contralateral dominance. These
      neurons were small to medium in size and their axons terminated in the lateral
      part of the SC, especially in the stratum griseum intermedium.

PMID- 7505416
TI  - Nicotinamide adenine dinucleotides mimic adenosine inhibition on synaptic
      transmission by decreasing glutamate release in rat hippocampal slices.
AB  - To assess the possible inhibitory action of nicotinamide adenine dinucleotides on
      the synaptic release of glutamate, electrophysiological and biochemical
      experiments were performed on rat hippocampal slices. Perfusion of adenosine,
      beta-nicotinamide adenine dinucleotide (NAD) or beta-nicotinamide adenine
      dinucleotide phosphate (NADP), reversibly inhibited the field excitatory
      postsynaptic potentials (fEPSP). Dose-response curves for their inhibitory action
      showed that these three substances had a similar potency in the range of
      concentrations from 0.1 microM to 100 microM. NADP and adenosine (100 microM)
      halved the K(+)-induced release of endogenous glutamate and aspartate, leaving
      gamma-amino-butyric acid (GABA) levels unchanged. 3-Isobutyl-1-methylxanthine
      (IBMX) 200 microM, an antagonist of the P1-purinoreceptors, antagonized the
      depressant effects of these coenzymes on both fEPSP and also on amino acid
      release. Based on these results we propose that nicotinamide adenine
      dinucleotides, similar to adenosine, inhibit excitatory synaptic transmission in
      the rat hippocampus by decreasing glutamate release from synaptic terminals.

PMID- 7505417
TI  - High ethanol sensitivity of recombinant AMPA-type glutamate receptors expressed
      in mammalian cells.
AB  - The effect of ethanol (EtOH) on ion current mediated by recombinant alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate (KA) receptors was
      examined in transfected human embryonic kidney 293 cells using whole-cell
      recording. Inhibition of KA-activated current was observed in the presence of
      intoxicating EtOH concentrations. The potency with which EtOH inhibited current
      was similar for receptors formed by different subunits or subunit combinations.
      EtOH also inhibited KA-activated current in cultured neurons from fetal rat
      cortex. However, the potency of EtOH inhibition in cortical neurons was lower
      than that observed in 293 cells expressing recombinant receptors. The properties
      of receptors in cultured neurons, other than EtOH sensitivity, were similar to
      those displayed by recombinant AMPA/KA receptors. These observations indicate
      that some forms of non-NMDA ionotropic glutamate receptors have relatively high
      EtOH sensitivity. These receptors appear to differ in some respect from
      AMPA/kainate receptors expressed endogenously in cortical neurons.

PMID- 7505418
TI  - Neuropeptide K potently stimulates the hydrolysis of phosphatidylinositol in the
      rat spinal cord.
AB  - The accumulation of total [3H]inositol phosphates stimulated by neuropeptide K
      was investigated in rat spinal cord slices and compared with that of substance P
      and carbachol. The rank order of potency of the agonists in stimulating
      [3H]phosphatidylinositol (PI) hydrolysis was neuropeptide K > substance P >
      carbachol. The PI responses to neuropeptide K and substance P were significantly
      (P < 0.01) enhanced when slices were incubated with a mixture of bacitracin (30
      microM), captopril (10 microM) and leupeptin (2 micrograms/ml), yet the order of
      potency remained unchanged. These results show for the first time that NPK can
      stimulate the PI hydrolysis in the adult rat spinal cord. The relatively greater
      degree of potency and efficacy of NPK over SP to stimulate PI hydrolysis does not
      appear to be entirely attributed to the metabolic stability of the peptide.

PMID- 7505419
TI  - Afferent and efferent connections of the cortical accommodation area in the cat.
AB  - Accommodative responses were evoked by microstimulation of a circumscribed area
      in the lateral suprasylvian (LS) cortex of the cat. We studied anatomical
      connections of this area with WGA-HRP. We identified an accommodation-related
      area by systematic microstimulation of the LS cortex in each of nine cats.
      Accommodative and pupillary responses were monitored by an infrared optometer and
      a pupillometer, respectively. WGA-HRP was injected into the accommodation-related
      area where accommodative responses were elicited with low-intensity
      microstimulation, but pupillary responses were not evoked. Retrogradely labeled
      cells were found mainly in ipsilateral areas 17, 18 and 19, the pulvinar, the
      lateral posterior nucleus of the thalamus (LP) and the contralateral LS area.
      Fewer labeled cells were found in ipsilateral areas 20 and 21, the ventral
      lateral suprasylvian area (VLS), the splenial visual area (SVA) and the lateral
      geniculate nucleus (LGN). Anterogradely labeled terminals were located mainly in
      the ipsilateral LP, the rostral portion of the pontine nuclei and the superficial
      layers of the ipsilateral superior colliculus which corresponds to the
      representation of the central visual field. Less dense labeled terminals were
      also found in the ipsilateral nucleus of the optic tract (NOT) in two cats.

PMID- 7505420
TI  - Equianalgesic dosing: oral to i.v. conversions.

PMID- 7505421
TI  - Rectal adenocarcinoma with germ cell elements treated with chemotherapy.
AB  - A patient with adenocarcinoma of the rectum containing germ cell elements in the
      form of endodermal sinus tumor and choriocarcinoma is described, believed to be
      the first such tumor reported in the literature. The serum levels of alpha
      fetoprotein and human chorionic gonadotropin were markedly elevated. The source
      of the markers was localized to the neoplastic tissue by the immunoperoxidase
      technique. The patient developed extensive hepatic metastases thought to be due
      to choriocarcinoma for which she received chemotherapy. One wk after commencing
      treatment a massive fatal hepatic hemorrhage occurred.

PMID- 7505422
TI  - Delta F508 genotype does not predict disease severity in an ethnically diverse
      cystic fibrosis population.
AB  - OBJECTIVE: As part of a study to determine population-based frequencies of CFTR
      mutations in an ethnically diverse, midwestern cystic fibrosis (CF) population,
      clinical histories were studied in 119 CF patients. METHODOLOGY: We sought to
      examine the association between genotype as characterized by the delta F508 and
      11 other commonly occurring mutations and clinical parameters including age at
      diagnosis, clinical presentation, sweat chloride level, chest roentgenogram
      score, clinical scores, pulmonary function test results, percent weight for
      height, and presence of associated CF complications. RESULTS: Age at diagnosis of
      CF was significantly associated with homozygosity for delta F508 (mean age at
      diagnosis +/- SE: 1.7 +/- 0.3 years for delta F508/delta F508 vs 3.9 +/- 0.9
      years for delta F508/other and other/other; P = .03). No other age-adjusted
      clinical parameter was significantly associated with delta F508 or any other
      genotype. CONCLUSION: These data suggest that in this sample of CF patients,
      delta F508 genotype is not predictive of disease severity. The lack of
      association between disease severity and genotype in this ethnically diverse
      sample may reflect the presence of more severe undetected mutations in our
      sample, or the effects of modifying genes at other, non-CF loci.

PMID- 7505424
TI  - Simultaneous Technique for Acuity and Readiness Testing (START): further
      concurrent validation of an aid for developmental surveillance.
AB  - STUDY OBJECTIVE: A brief (8-minute) procedure, now called Simultaneous Technique
      for Acuity and Readiness Testing or START, has been shown to be efficacious for
      predicting developmental outcomes and a cost-effective screen for visual acuity.
      The objective of the two studies reported here was to examine the ability of this
      procedure to predict concurrent development outcome by using a new simplified
      scoring system. DESIGN: A prospective design was used. Subjects were screened
      using START, and then samples were stratified on the basis of developmental
      screening results (START in study 1 and the revised Denver Developmental
      Screening Test and a shortened version of the Minnesota Child Development
      Inventory in study 2) into subsamples (n = 118 and 120) which were administered
      the standard criterion test (McCarthy Scales of Children's Abilities in one
      cohort and the Stanford-Binet in the other). SETTING: Prekindergarten
      registration for a rural school system in North Carolina. SUBJECTS: Two county
      wide cohorts of preschool children (n = 352 and 362). MEASUREMENTS AND MAIN
      RESULTS: Results for prediction of the McCarthy outcomes were as follows:
      sensitivity, 0.76; specificity, 0.99; predictive value, 0.81; underreferral,
      1.3%; overreferral, 1.0%; and percent agreement, 98%. Prediction of Stanford
      Binet results was as follows: sensitivity, 0.94; specificity, 0.83; predictive
      value, 0.22; underreferral, 0.3%; overreferral, 16%; and percent agreement, 84%.
      Most of the overreferrals for the Stanford-Binet were in the clinically important
      borderline category. CONCLUSION: These results provide further support for the
      concurrent validity of START: The results illustrate how routine health
      procedures can be restructured to obtain clinically useful data on specific child
      developmental functioning.

PMID- 7505423
TI  - Aspartame, behavior, and cognitive function in children with attention deficit
      disorder.
AB  - OBJECTIVE: To determine the effects of large doses of aspartame on behavior,
      cognition, and monoamine metabolism in children with attention deficit disorder.
      DESIGN: A randomized, double-blind, placebo-controlled crossover study of
      unmedicated children meeting Diagnostic and Statistical Manual of Mental
      Disorders (3rd ed) criteria for attention deficit disorder. SETTING: Behavioral
      assessments were performed in the child's home by their parents and in the
      classroom by a teacher. Cognitive tests were administered and blood drawing was
      performed during a 2-day inpatient admission to our Children's Study Center.
      INTERVENTIONS: Administration of aspartame (single morning dose, 34 mg/kg) or
      placebo for alternate 2-week periods. MAIN OUTCOME MEASURES: Behavioral and
      cognitive tests included the Matching Familiar Figures Test (MFFT), Children's
      Checking Task (CCT), the Airplane Test, the Wisconsin Card Sorting Test (WCST),
      the Subjects Treatment Emergent Symptom Scale (STESS), the Multigrade Inventory
      for Teachers (MIT), and the Conners Behavior Rating Scale. Blood was drawn for
      complete blood cell count and liver function tests, as well as amino acid,
      methanol, formate, serotonin, and monoamine metabolite analyses, and urine was
      collected for measurement of catecholamine and monoamine metabolite excretion.
      RESULTS: No clinically significant differences between aspartame and placebo were
      found for the STESS, MIT, or Conners ratings, or for the MFFT, CCT, WCST, or
      Airplane cognition tests. Also, no differences were noted for any of the
      biochemical measures, except for the expected increase in plasma phenylalanine
      and tyrosine following aspartame. CONCLUSIONS: The findings indicate that
      aspartame at greater than 10 times usual consumption has no effect on the
      cognitive and behavioral status of children with attention deficit disorder. In
      addition, aspartame does not appear to affect urinary excretion rates of
      monoamines and metabolites.

PMID- 7505425
TI  - Yeast mitochondrial NAD(+)-dependent isocitrate dehydrogenase is an RNA-binding
      protein.
AB  - We have previously described the characterisation of an abundant mitochondrial
      protein (p40) that binds specifically to 5'-untranslated leaders of mitochondrial
      mRNAs in yeast. p40 consists of two polypeptides with M(r) of 40 and 39 kDa.
      Limited sequence analysis of p40 identifies it as the Krebs cycle enzyme NAD(+)
      dependent isocitrate dehydrogenase (Idh). Both enzyme and RNA-binding activities
      are specifically lost in cells containing disruptions in either IDH1 or IDH2, the
      nuclear genes encoding the two subunits of the enzyme, thus conclusively
      identifying p40 as Idh and showing that both activities are dependent on the
      simultaneous presence of both subunits. Although we still must ascertain whether
      and how either function of Idh is regulated and whether the two functions are
      compatible or mutually exclusive, this combination of dehydrogenase activity and
      RNA-binding in a single protein may be part of a general regulatory circuit
      linking the need for mitochondrial function to mitochondrial biogenesis.

PMID- 7505427
TI  - SP6 RNA polymerase efficiently synthesizes RNA from short double-stranded DNA
      templates.
AB  - SP6 DNA-dependent RNA polymerase, like T7 RNA polymerase, can be used to
      synthesize RNA sequences from short DNA templates which contain the 18 base pair
      promoter region. Use of SP6 polymerase extends the range of possible 5' sequences
      of RNA products, since the preferred SP6 start site (of the RNA product) is
      5'GAAGA, while T7 polymerase prefers 5'GGGAG. The SP6 start site can be
      advantageous in large-scale syntheses where high concentrations of RNA can lead
      to aggregation. Using the limited number of DNA templates described here, there
      appears to be a significant difference between the two enzymes: SP6 polymerase
      requires a complete duplex DNA substrate for efficient synthesis, unlike the T7
      enzyme which works efficiently when only the 18 base promoter region is double
      stranded. SP6 polymerase consistently produces higher yields of RNA than does T7
      polymerase, and the reactions can be easily scaled up to produce milligram
      quantities of RNA.

PMID- 7505426
TI  - Heat induction of sigma 32 synthesis mediated by mRNA secondary structure: a
      primary step of the heat shock response in Escherichia coli.
AB  - Induction of heat shock proteins following transfer of E. coli cells from 30
      degrees C to 42 degrees C depends on rapid accumulation of sigma 32, a minor
      sigma factor specifically required for transcription of heat shock genes. The
      synthesis of sigma 32 is induced by enhancing translation of its mRNA transcribed
      from the rpoH (htpR) gene. We previously showed that the translational control of
      rpoH-lacZ gene fusion is mediated by two cis-acting rpoH coding regions
      presumably involving mRNA secondary structure. To further examine this model, we
      constructed and analyzed a set of gene fusions carrying base substitution(s) or
      internal deletions within rpoH, including constitutive mutations predicted to
      destroy the mRNA secondary structure and compensatory second-site mutations that
      may restore the secondary structure. The results demonstrate that base pairings
      between the translation initiation region of some 20 nucleotides and part of the
      internal complementary sequences are critical for maintaining repression during
      steady-state growth and for modulating heat-induced synthesis of sigma 32-beta
      galactosidase fusion protein upon temperature upshift. Furthermore, some of the
      compensatory mutations resulted in super-repressed (non-inducible) phenotypes,
      suggesting that the heat induction depends on a specific nucleotide sequence(s)
      as well as the mRNA secondary structure within the 5'-proximal regulatory segment
      of rpoH coding region.

PMID- 7505428
TI  - NMR evidence for the RNA stem-loop structure involved in the transcription
      attenuation of E. coli trp operon.
AB  - High field 1H-NMR studies of a synthetic 21-mer RNA fragment, corresponding to
      residues +114 to +134 within the trp leader mRNA transcript, have been carried
      out. Seven well resolved imino proton resonances corresponding to six C-G and one
      A-U hydrogen bonded base pairs, together with their characteristic NOE patterns
      can be identified in the NMR spectrum. This experimental result provides direct
      evidence for the postulated stem-loop secondary structure, 3:4, which has been
      reported to act as a transcription termination signal for RNA polymerase.

PMID- 7505430
TI  - PCR mediated analysis of RNA sequences.

PMID- 7505431
TI  - World AIDS Day. Symbol of hope.

PMID- 7505429
TI  - Selective optimization of the Rev-binding element of HIV-1.
AB  - RNA molecules that can bind to the Rev protein of HIV-1 have been isolated from
      random sequence nucleic acid pools based on a minimal Rev-binding element (RBE)
      found within the Rev Responsive Element (RRE). While the selected sequences are
      related to the wild-type element, they also contain substitutions that allow them
      to bind Rev up to 10-fold better in vitro. A hypothesized homopurine pairing at
      G48:G71 is generally replaced by A48:A71; the occasional selection of C48:A71
      suggests that R71 may be in a syn conformation. These data support the structural
      model for the RBE originally proposed by Bartel et al. (1). Additional
      interactions with the Rev protein are promoted by the sequence CUC ... UYGAG,
      found in one class of high-affinity aptamers, but absent from the wild-type
      element. Within each class of aptamers different residues and substructures
      covary with one another to generate optimal Rev-binding surfaces. The
      interdependencies of different nucleotide substitutions suggest structural models
      for both the wild-type RBE and the selected high-affinity aptamers.

PMID- 7505432
TI  - [Gamma globulins in clinical practice].

PMID- 7505433
TI  - [Experimental treatment with high-dose gamma globulins in autoimmune diseases].
AB  - High-dose intravenous gammaglobulin has been successfully used in several
      autoimmune diseases such as idiopathic thrombocytopenic purpura, autoimmune
      neutropenia; more recently this treatment has been experimented in other
      autoimmune conditions with conflicting results. After a review of recent
      literature, the article considers results obtained by high-dose intravenous
      gammaglobulin therapy in some conditions such as connective tissue diseases and
      vasculitis. A review of different mechanisms of action hypothesized in the
      different disorders is reported. In fact, it is quite clear today that this
      treatment has not only clinical effects but achieves also measurable
      immunological and biological results so that we can consider high-dose
      gammaglobulin as a immunomodulating treatment.

PMID- 7505434
TI  - [Experience with gamma globulins per os in the therapy and prevention of
      infectious diarrhea].
AB  - The efficacy of oral gammaglobulin in the treatment of acute infectious diarrhea
      in immunocompetent children has been evaluated in an open placebo controlled
      trial. Moreover the efficacy of oral gammaglobulin has been tested also for
      treatment of chronic diarrhea in IgA deficient infants and for prevention of
      rotavirus infection during an epidemic in the ward. 54 infants (aged 1-36 months)
      with acute diarrhea (30 rotavirus +) were enrolled in the study. 24 out of 54
      were assigned with randomised method to group a receiving gammaglobulin 150 mg/kg
      x 2 in the first day of admission to hospital and the remaining 30 infants were
      assigned to group b receiving placebo. Diarrhea cleared up in 2.57 +/- 1.4 days
      without a significant difference between group a and b (2.6 +/- 1.6 and 2.46 +/-
      1.1 days respectively). The diarrhea's duration in Rotavirus+infants was 2.78 +/-
      1.4 days in group a and 3 +/- 1.4 days in group b again without a significant
      difference. The excretion time of rotavirus in the stools was significantly
      shorter in rotavirus+group a (2.6 +/- 1.3) than in rotavirus group b (3.9 +/-
      1.6) with p < 0.04. Three infants (4.9 months) with chronic post-infectious
      diarrhea and IgA deficiency (< 5 mg%ml) received gammaglobulin 300 mg/kg/die for
      3 days. The diarrhea recovered in 2-3 days. Out of 16 infants hospitalized during
      an epidemic rotavirus diarrhea 6 infants received oral gammaglobulin at the dose
      of 150 mg/kg/die during the hospitalization period (that was at least 5 days). No
      one became ill.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505435
TI  - Antigen-specific T cell proliferation following coccidia infection.
AB  - Coccidia antigen-specific T lymphocyte proliferation induced by Eimeria
      acervulina was measured in chickens congenic at the major histocompatibility
      complex and in two unrelated lines. Sporozoites and merozoites induced high
      proliferation of lymphocytes following primary infection, with similar changes
      seen for splenic or peripheral blood lymphocytes. Highest antigen-specific
      proliferation after both primary and secondary infection was seen in Line 15I5,
      which contributed the background genome to the congenic lines. In general,
      merozoites elicited higher proliferation responses than sporozoites. Analyses of
      differences between uninfected and infected chickens showed that, at some points
      in the infection cycle, proliferation of lymphocytes was greater and at other
      times less for infected than uninfected chickens.

PMID- 7505436
TI  - Management of lung cancer.

PMID- 7505437
TI  - [Positive selection of hematopoietic CD 34 stem cells for autograft].
AB  - The CD 34 antigen is a glycoprotein found on the surface of hematopoietic stem
      cells and early committed progenitors. The CE 34 stem cells from 14 samples of
      bone marrow, cord blood or leucapheresis were isolated using a positive selection
      procedure involving an anti CD 34 biotinylated monoclonal antibody and an avidin
      immunoabsorption device. Results showed that in 60 percent of samples, the
      positively-selected fractions contained more than 70 percent CD 34 cells.
      Concentration in CFU-GM and BFU-E progenitors increased 15 and 26 fold
      respectively in the CE 34 enriched samples. Long-term culture of two samples
      demonstrated that nearly all of the most immature progenitors were recovered in
      the procedure. These preliminary results showed that the positive selection
      technique of CD 34 hematopoietic stem cells is now available for use in
      autologous or allogeneic hematopoietic stem cell transplantation.

PMID- 7505438
TI  - Microtubules and Src homology 3 domains stimulate the dynamin GTPase via its C
      terminal domain.
AB  - Dynamin is a 100-kDa GTPase that plays a critical role in the initial stages of
      endocytosis. Dynamin binds to microtubules, which potently stimulate its GTPase
      activity. Binding to Src homology 3 (SH3) domains of proteins involved in signal
      transduction has also recently been reported. In the present study, the protein
      was digested with a variety of proteases to define its functional domains.
      Limited digestion with papain split the protein into an approximately 7- to 9-kDa
      microtubule-binding fragment and a 90-kDa nonbinding fragment. Immunoblotting
      with an antibody to the C-terminal 20 amino acids of rat dynamin showed the small
      fragment to derive from the C-terminal end of the polypeptide. Microtubule
      activated GTPase activity, but not basal GTPase activity, was abolished by papain
      digestion, identifying the basic, proline-rich C-terminal region of dynamin as an
      important regulatory site. Bacterially expressed growth factor receptor-bound
      protein 2 (GRB2) and the SH3 domain of c-Src were also found to stimulate GTPase
      activity, although to a lesser extent than microtubules. Stimulation of GTPase
      activity by the recombinant proteins was similarly abolished by papain digestion.
      These results identify the basic, proline-rich C-terminal region of dynamin as
      the binding site for both microtubules and SH3 domains and demonstrate an
      allosteric interaction between this region of the molecule and the N-terminal
      GTPase domain.

PMID- 7505439
TI  - Identification of a cytochrome P450 gene by reverse transcription--PCR using
      degenerate primers containing inosine.
AB  - A cytochrome P450-like gene, tentatively named P450CMEF, was amplified by a mixed
      oligonucleotide-primed amplification of cDNA from C3H mouse embryo fibroblast
      cells, designated 10T1/2, that had been treated with 7,12
      dimethylbenz[a]anthracene (DMBA) or benz[a]anthracene (BA). A set of inosine
      containing degenerate primers that were targeted to two conserved regions of
      known cytochrome P450 cDNAs were used. One primer was coded for the well
      described and conserved heme-binding region of P450 enzymes, and the second was
      designed based upon other considerations of homology among P450 molecules. One of
      the four PCR-amplified cDNA products hybridized to two major RNA bands, 4.2 and
      5.3 kb, that were induced by DMBA or BA. The amino acid sequence of the fragment
      deduced from the base-sequence data indicate that the amplified cDNA has a 50-55%
      identity with the cytochrome P450 subfamily 1A. The induction of P450CMEF mRNA
      preceded the induction of aryl hydrocarbon hydroxylase activity after DMBA or BA
      treatment, suggesting that the product of P450CMEF is involved in the metabolism
      of these polycyclic aromatic hydrocarbons in 10T1/2 cells. From the partial
      sequence of the cDNA identified by this procedure, we propose that P450CMEF is a
      member of the P450 superfamily, possibly in a subfamily of family 1, that is
      induced in 10T1/2 cells by DMBA and BA. This method should be useful in
      identifying additional P450 genes and genes in other gene families.

PMID- 7505440
TI  - Inhibition of granulocyte differentiation by G1 cyclins D2 and D3 but not D1.
AB  - Growth factor-induced signals govern the expression of three D-type cyclins,
      which, in turn, function as regulatory subunits of cyclin-dependent kinases
      (cdks) to control cell cycle transitions during the late G1 interval. 32D myeloid
      cells, which self-renew as uncommitted precursors in interleukin 3 (IL-3),
      express cyclins D2 and D3 (but not D1) in complexes with cdk4 and cdk2. When
      transferred to granulocyte colony-stimulating factor (G-CSF), 32D cells stop
      dividing and terminally differentiate to mature neutrophils. Cyclin D and cdk4
      expression ceased as cells underwent growth arrest in G-CSF, but cdk2 levels were
      sustained. 32D cells engineered to ectopically express D-type cyclins exhibited
      contracted G1 intervals with a compensatory lengthening of S phase but remained
      IL-3 dependent for cell growth; those overexpressing cyclins D2 and D3 (but not
      D1) were unable to differentiate and died in G-CSF. Cyclin D2 mutants, which
      cannot efficiently bind to, or functionally interact with, the retinoblastoma
      protein (pRb) or its relatives (p107) did not block differentiation. Conversely,
      the introduction of a catalytically inactive cdk4 mutant into cells
      overexpressing cyclin D2 restored their G-CSF response. The persistence of cdk2
      and its predilection to functionally interact with cyclins D2 and D3 rather than
      D1 might explain the specificity of the differentiation blockade.

PMID- 7505441
TI  - V3 variability can influence the ability of an antibody to neutralize or enhance
      infection by diverse strains of human immunodeficiency virus type 1.
AB  - Human monoclonal antibodies (mAbs) to two contiguous epitopes in the V3 loop of
      the human immunodeficiency virus type 1 (HIV-1) envelope have shown different
      effects on three distinct strains of the virus: neutralization, enhancement, or
      resistance to both processes. Only one amino acid in the mAb epitopes proximal to
      the crown of the V3 loop was different among these three strains. Substitution of
      this amino acid in the neutralizable strain with the amino acid of the
      neutralization-resistant strain or the enhanceable strain resulted in loss of
      both activities. The conversion of this single amino acid in the neutralization
      resistant strain to that of the amino acid found in the neutralization-sensitive
      strain did not confer the ability for the virus to be neutralized. However,
      additional changes in neighboring amino acids in the V3 loop succeeded in
      conferring the neutralization capability. These observations indicate that one
      antibody species can exert three different effects on various HIV-1 strains. They
      could explain the emergence of neutralization "escape" variants in the presence
      of the neutralizing antibodies. Moreover, the results suggest caution in
      immunization of individuals with the envelope region from one strain since the
      antibodies induced may show a neutralizing effect against the homologous strain
      but enhancing effects against other unrelated strains.

PMID- 7505442
TI  - The CD58 (LFA-3) binding site is a localized and highly charged surface area on
      the AGFCC'C" face of the human CD2 adhesion domain.
AB  - Using site-directed mutagenesis in conjunction with NMR structural data on the
      adhesion domain of human CD2, we have defined the binding region for CD58.
      Previous structural studies of rat and human CD2 indicate that this adhesion
      domain is immunoglobulin-like. Here we report that the CD58 binding site is a
      well-circumscribed, charged surface area covering approximately 770 A2 on the
      AGFCC'C" face of the CD2 beta barrel. This site contains beta-strand residues in
      the carboxyl-terminal half of the F strand (including Lys-82 and Tyr-86), the top
      of the C strand (Asp-32 and Lys-34), and the C' strand (Gln-46), which are all
      solvent exposed. In addition, several exposed residues on the FG loop (Gly-90,
      Lys-91, Asn-92, and Val-93), the CC' loop (Lys-41 and Lys-43), and the C'C" loop
      (Arg-48 and Lys-51) form this site. In contrast, neither residues on the more
      peripheral G and C" strands of the same CD2 surface nor residues on B, E, and D
      strands of the opposite face are involved in CD58 binding. This CD58 binding site
      is predicted to lie most distal to the T-lymphocyte surface membrane, with ready
      access to CD58 on the surface of the opposing antigen-presenting cell.

PMID- 7505443
TI  - Isolation of an Arabidopsis thaliana gene encoding cycloartenol synthase by
      functional expression in a yeast mutant lacking lanosterol synthase by the use of
      a chromatographic screen.
AB  - Whereas vertebrates and fungi synthesize sterols from epoxysqualene through the
      intermediate lanosterol, plants cyclize epoxysqualene to cycloartenol as the
      initial sterol. We report the cloning and characterization of CAS1, an
      Arabidopsis thaliana gene encoding cycloartenol synthase [(S)-2,3-epoxysqualene
      mutase (cyclizing, cycloartenol forming), EC 5.4.99.8]. A yeast mutant lacking
      lanosterol synthase [(S)-2,3-epoxysqualene mutase (cyclizing, lanosterol
      forming), EC 5.4.99.7] was transformed with an A. thaliana cDNA yeast expression
      library, and colonies were assayed for epoxysqualene mutase activity by thin
      layer chromatography. One out of approximately 10,000 transformants produced a
      homogenate that cyclized 2,3-epoxysqualene to the plant sterol cycloartenol. This
      activity was shown to be plasmid dependent. The plasmid insert contains a 2277-bp
      open reading frame capable of encoding an 86-kDa protein with significant
      homology to lanosterol synthase from Candida albicans and squalene-hopene cyclase
      (EC 5.4.99.-) from Bacillus acidocalcarius. The method used to clone this gene
      should be generally applicable to genes responsible for secondary metabolite
      biosynthesis.

PMID- 7505444
TI  - Cys4057 of apolipoprotein(a) is essential for lipoprotein(a) assembly.
AB  - Lipoprotein(a) contains one copy each of apolipoprotein B-100 and
      apolipoprotein(a). It has been hypothesized that a disulfide bond might exist
      between Cys4057 of apolipoprotein(a) and Cys3734 in apolipoprotein B-100. To
      investigate the role of Cys4057 for lipoprotein(a) assembly, wild-type and in
      vitro mutagenized apolipoprotein(a) cDNA plasmids were expressed in the human
      hepatocarcinoma line HepG2. The mutant plasmids encoded apolipoprotein(a) species
      with Cys4057 exchanged to either serine or glycine. Untransfected HepG2 cells,
      although able to secrete apolipoprotein B-100-containing lipoproteins, do not
      synthesize detectable amounts of apolipoprotein(a). After transfection of wild
      type plasmid, almost all apolipoprotein(a) in the culture supernatant was present
      in lipoprotein(a)-like particles as demonstrated by immunoblotting, density
      gradient centrifugation, and ELISA. The same analysis performed with supernatants
      of cells transfected with plasmids mutated in codon 4057 revealed free
      apolipoprotein(a) glycoprotein without detectable amounts of lipoprotein
      associated apolipoprotein(a). Our results strongly suggest the existence of a
      disulfide bridge between Cys4057 of apolipoprotein(a) and apolipoprotein B-100
      within recombinant lipoprotein(a) particles. Furthermore, they indicate that
      disulfide bridge formation is essential for assembly of the lipoprotein(a)-like
      complex produced by HepG2 cells and suggest a similar role of Cys4057 during
      lipoprotein(a) assembly in vivo.

PMID- 7505445
TI  - Functional kainate-selective glutamate receptors in cultured hippocampal neurons.
AB  - Glutamate mediates fast synaptic transmission at the majority of excitatory
      synapses throughout the central nervous system by interacting with different
      types of receptor channels. Cloning of glutamate receptors has provided evidence
      for the existence of several structurally related subunit families, each composed
      of several members. It has been proposed that KA1 and KA2 and GluR-5, GluR-6, and
      GluR-7 families represent subunit classes of high-affinity kainate receptors and
      that in vivo different kainate receptor subtypes might be constructed from these
      subunits in heteromeric assembly. However, despite some indications from
      autoradiographic studies and binding data in brain membranes, no functional pure
      kainate receptors have so far been detected in brain cells. We have found that
      early after culturing, a high percentage of rat hippocampal neurons express
      functional, kainate-selective glutamate receptors. These kainate receptors show
      pronounced desensitization with fast onset and very slow recovery and are also
      activated by quisqualate and domoate, but not by alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate. Our results provide evidence for the existence of
      functional glutamate receptors of the kainate type in nerve cells, which are
      likely to be native homomeric GluR-6 receptors.

PMID- 7505447
TI  - Low Ba2+ and Ca2+ induce a sustained high probability of repolarization openings
      of L-type Ca2+ channels in hippocampal neurons: physiological implications.
AB  - Openings of single L-type Ca2+ channels following repolarization to negative
      membrane potentials from a depolarizing step (repolarization openings, ROs) have
      been described previously in brain cell preparations. However, these ROs have
      been reported to occur only infrequently. Here we report that the frequency of
      ROs in cell-attached patches of cultured rat hippocampal neurons can be increased
      dramatically by lowering the pipette Ba2+ concentration to 20 mM from the usual
      90-110 mM. This increased opening probability can last for hundreds to thousands
      of milliseconds following repolarization. Current-voltage analyses of open
      probability show that the depolarization pulse threshold for inducing ROs in 20
      mM Ba2+ is -10 to 0 mV but that the probability of ROs reaches maximal levels
      following depolarizing pulses that approach the apparent null (equilibrium)
      potential for Ba2+. Comparable current-voltage curves in 110 mM Ba2+ from a more
      positive holding potential (-50 mV) indicate that membrane surface charge
      screening accounts for some, but not all, of the effect of lowering the Ba2+
      concentration. Consequently, current-dependent inactivation or some other ion
      dependent mechanism (e.g., ion binding inside the pore) also appears to regulate
      this potentially major pathway of Ca2+ entry. A high probability of ROs also can
      be induced under relatively physiological conditions (5-ms depolarizing steps, 2
      5 mM Ca2+ in the pipette). Thus, the high open probability state at negative
      potentials may underlie the long Ca2+ tail currents in hippocampus that were
      described previously and appears to have major implications for physiological
      functions (e.g., the slow Ca(2+)-dependent afterhyperpolarization), particularly
      in brain neurons.

PMID- 7505446
TI  - Human T-cell receptor (TCR) alpha/beta + CD4-CD8- T cells express oligoclonal
      TCRs, share junctional motifs across TCR V beta-gene families, and phenotypically
      resemble memory T cells.
AB  - Most human T cells express the TCR alpha/beta and either CD4 or CD8 molecules
      (single positive, SP); however, small numbers lack CD4 and CD8. In inbred mice,
      alpha/beta CD4-CD8- (double negative, DN) T cells preferentially express certain
      beta variable region (V beta) families and may arise via unique developmental
      pathways. Increased percentages of alpha/beta DN T cells have been identified in
      some human and murine autoimmune and immunodeficiency diseases. However, their
      contribution to disease pathology or normal immunity is unknown. To study the
      cell surface phenotype and TCR diversity of human alpha/beta DN T cells, these
      cells were isolated from the peripheral blood of healthy adults. The proportion
      of alpha/beta DN T cells expressing molecules associated with activation (HLA
      DR), previous exposure to antigen (CD45RO), and cytotoxic function (CD56, CD57,
      and CD11b) was increased relative to SP T cells. The TCR V beta repertoire of
      alpha/beta DN T cells was different from that of alpha/beta SP T cells, although
      most major gene families were present. For example, higher proportions of V beta
      11, a minor gene family in peripheral blood leukocytes, were found in most
      alpha/beta DN T-cell samples. In contrast to mice, no dominant V beta family was
      used consistently in different human individuals. Within an individual alpha/beta
      DN T cells possessed an oligoclonal TCR beta repertoire with conservation of
      several distinct junctional amino acid motifs with one joined to three different
      V beta genes in two individuals, suggesting that these cells have undergone a
      selection process driven by a limited set of ligands. The possibility that they
      may represent, at least in part, originally SP T cells anergized by down
      modulation of CD4 or CD8 must also be entertained. Overall, this study
      demonstrates that human peripheral blood alpha/beta DN T cells possess unique
      phenotypic and TCR beta repertoire characteristics when compared with the major
      alpha/beta SP T cell populations and thus may serve specialized immunologic
      functions and/or have an unusual origin.

PMID- 7505448
TI  - A gene encoding a protein related to eukaryotic protein kinases from the
      filamentous heterocystous cyanobacterium Anabaena PCC 7120.
AB  - Protein kinases play essential roles in the development of eukaryotic cells.
      These enzymes display various degrees of sequence similarity in their catalytic
      domains. This conservation has allowed the identification of protein kinases in a
      variety of organisms, including the Gram-negative bacterium Myxococcus xanthus.
      In this study, sequences related to those encoding eukaryotic protein kinases
      were amplified by PCR from DNA of Anabaena PCC 7120, a filamentous cyanobacterium
      that differentiates cells specifically for nitrogen fixation, called heterocysts,
      under conditions of combined nitrogen limitation. Results from Southern
      hybridization and sequencing of PCR products suggest the presence of a family of
      similar protein kinases in this strain. One of the corresponding genes (pknA) was
      isolated from a gene library. The N-terminal region of its amino acid sequence
      shows significant similarity to the catalytic domains of eukaryotic-type protein
      kinases. Expression of this gene was found to be developmentally regulated.
      Inactivation of pknA led to colonies that appeared light green and rough in the
      absence of combined nitrogen. Mutant filaments produce fewer heterocysts than
      wild-type ones. These results suggest that pknA is required for both normal
      cellular growth and differentiation of Anabaena PCC 7120.

PMID- 7505449
TI  - Tyrosine kinase activity of CD4-associated p56lck may not be required for CD4
      dependent T-cell activation.
AB  - The lymphoid-specific tyrosine kinase p56lck (Lck) is critical for the
      development and activation of T lymphocytes, and Lck kinase activity has been
      implicated in both T-cell antigen receptor/CD3- and CD4-mediated signaling. CD4
      dependent T-cell activation has been demonstrated to be dependent upon the
      association of CD4 with Lck. To examine the role of the kinase activity of Lck in
      CD4-dependent T-cell activation, we have generated several kinase-deficient
      mutants of Lck. When transfected into CD4+ murine T-cell hybridoma cells, these
      mutants cause approximately 90% diminution in CD4-associated Lck kinase activity.
      Specifically, upon CD4 crosslinking there is decreased Lck autophosphorylation
      and decreased phosphorylation of an exogenous substrate. When CD4 is crosslinked
      to the T-cell antigen receptor-CD3 complex, decreased phosphorylation of
      associated substrates is also observed. In spite of this striking inhibition of
      Lck kinase function, cells expressing the kinase-deficient mutants demonstrate
      normal or enhanced CD4-dependent antigen responsiveness. These data demonstrate
      that the level of Lck kinase activity does not correlate with its CD4-associated
      function and suggest that the kinase activity of Lck may not be required for CD4
      mediated signaling.

PMID- 7505451
TI  - Number of CpG islands and genes in human and mouse.
AB  - Estimation of gene number in mammals is difficult due to the high proportion of
      noncoding DNA within the nucleus. In this study, we provide a direct measurement
      of the number of genes in human and mouse. We have taken advantage of the fact
      that many mammalian genes are associated with CpG islands whose distinctive
      properties allow their physical separation from bulk DNA. Our results suggest
      that there are approximately 45,000 CpG islands per haploid genome in humans and
      37,000 in the mouse. Sequence comparison confirms that about 20% of the human CpG
      islands are absent from the homologous mouse genes. Analysis of a selection of
      genes suggests that both human and mouse are losing CpG islands over evolutionary
      time due to de novo methylation in the germ line followed by CpG loss through
      mutation. This process appears to be more rapid in rodents. Combining the number
      of CpG islands with the proportion of island-associated genes, we estimate that
      the total number of genes per haploid genome is approximately 80,000 in both
      organisms.

PMID- 7505450
TI  - Use of a yeast expression system for the isolation and analysis of drug-resistant
      mutants of a mammalian phosphodiesterase.
AB  - Saccharomyces cerevisiae strain PP5 has a phosphodiesterase (PDE) deficiency that
      results in heat-shock sensitivity due to the intracellular accumulation of cAMP.
      This strain also carries the cam mutation, which confers permeability to cAMP
      and, as shown here, to other compounds. Expression of rat type IV PDE in these
      cells caused them to revert to heat-shock resistance. Treatment of the
      transformed PP5 cells with rolipram, an antidepressant in humans and a potent
      inhibitor of type IV PDEs, reinstated sensitivity to heat shock. The biochemical
      properties of deletion mutants of this PDE were determined, and an active enzyme
      of minimum length was created. Reversion to heat-shock resistance was then used
      to select for PDE mutants refractory to the inhibitory effects of rolipram. Four
      mutants (A1, A2, A3, and A5) were isolated. Each carries a single point mutation;
      two have mutations in the same codon. Each mutant showed distinct properties,
      based on analysis of their substrate kinetics and IC50 values for a variety of
      inhibitors. Mutant A5 had a reduced activity for substrate, mutants A1 and A3
      showed no change in substrate kinetics, and mutant A2 displayed an increase in
      activity. For most mutants, the drug resistance was confined to the class of drug
      used in the selection. This study shows that it is possible to recreate in yeast
      cells the susceptibility of mammalian enzymes to pharmacological agents. Our
      study also demonstrates that such systems can be used to select rare mutants
      useful in the analysis of drug-protein interactions.

PMID- 7505452
TI  - Isolation of cDNAs for perilipins A and B: sequence and expression of lipid
      droplet-associated proteins of adipocytes.
AB  - The major cAMP-dependent protein kinase (A-kinase) substrate in adipocytes is
      perilipin, a protein found exclusively at the surface of the lipid storage
      droplets. Using anti-perilipin serum, we have isolated two related classes of
      full-length coding cDNAs, designated perilipin A and B, from a rat adipocyte cDNA
      expression library. The two cDNAs derive from two mRNA species that arise by
      differential splicing. The mRNAs are predicted to encode perilipins A and B,
      proteins of 517 aa (56,870 Da) and 422 aa (46,420 Da), respectively, which share
      a common 406-aa N-terminal sequence. The predicted perilipin A contains peptides
      present in proteolytic digests of the purified 62-kDa form of perilipin from rat
      adipocytes, as well as the requisite consensus A-kinase phosphorylation sites.
      Like perilipin A, the B form is expressed in adipocytes and is associated with
      lipid storage droplets. Modeling of predicted secondary structures fails to
      reveal an underlying basis for the tenacious association of perilipins with lipid
      droplets. These proteins exhibit a significant sequence relationship
      (approximately 65% similarity through 105 aa) with only one other known protein,
      the adipocyte differentiation-related protein (ADRP). Like the perilipins, ADRP
      appears to be adipocyte-specific, which suggests that they interact in a related
      intracellular pathway. The molecular probes for perilipins A and B described here
      will permit detailed analyses of their functional role(s) in lipid metabolism.

PMID- 7505453
TI  - Single-channel properties of cloned cGMP-activated channels from retinal rods.
AB  - Single-channel properties of a cloned channel activated by cyclic GMP have been
      analysed. The mRNA encoding for the channel was injected into oocytes of Xenopus
      laevis and the current flowing through a single ionic channel activated by cGMP
      was studied in excised patches under voltage-clamp conditions. The ionic channel
      activated by cGMP had a single-channel conductance of 32 +/- 2 pS at +120 mV and
      25 +/- 4 pS at -120 mV, and its conductance was not significantly affected by
      increasing the cGMP concentration from 20 microM to 200 microM. The single
      channel currents in the presence of NH+4, Na+, K+, Li+ and Rb+ in the medium
      bathing the cytoplasmic side of the membrane at +140 mV were 5.3, 4.7, 3.8, 1.3
      and 0.8 pA, respectively. The single-channel current in the presence of Cs+ was
      less than 0.5 pA. Ca2+ and Mg2+ (both 0.5 mM) in the presence of 100 microM cGMP
      did not appreciably affect the channel activity at membrane potentials more
      negative than -80 mV, whereas at +100 mV they reduced the single-channel
      conductance by about threefold. The ionic selectivity and the blockage by
      divalent cations of the native channel found in amphibian rods and in the cloned
      channel from bovine rods are quite similar. However, the cloned channel has well
      resolved openings, especially at positive membrane voltages, whereas the native
      channel is characterized by a continuous flickering between the open and closed
      state.

PMID- 7505454
TI  - Effects of chronic cocaine administration on the serotonergic system in the rat
      brain.
AB  - Male Sprague-Dawley rats received injections of cocaine (20 mg/kg/dose, IP) every
      12 h for 14 days and were sacrificed on the 15th day. The chronic cocaine
      treatment caused an increase in the levels of serotonin [5-hydroxytryptamine (5
      HT)] and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus. 5
      HIAA levels in the frontal cortex were also increased, but 5-HT levels were
      unaltered by the chronic cocaine treatment. Similarly, striatal levels of 5-HT
      and 5-HIAA were unchanged by repeated administration of cocaine. Chronic cocaine
      administration did not alter the density of [3H]8-OH(DPAT), [3H]mesulergine, or
      [3H]ketanserin binding in the hippocampus, choroid plexus, and frontal cortex,
      respectively. Furthermore, repeated injection of cocaine did not alter
      serotonergic-mediated inhibition of adenylate cyclase activity. Thus, repeated
      administration of cocaine causes region-specific alterations in 5-HT levels but
      does not change the properties of the 5-HT1A, 5-HT1C, or 5-HT2 receptors.

PMID- 7505455
TI  - Iloprost, a stable analogue of PGI2, potentiates the hyperthermic effect of PGE2
      in rats.
AB  - Centrally mediated effects of iloprost, a stable analogue of PGI2, on rectal
      temperature have been investigated in conscious rats. ICV administration of
      iloprost (100-1,000 ng, ICV) produced a dose-dependent, monophasic hyperthermic
      response that was not inhibited by indomethacin. When injected into the preoptic
      anterior hypothalamic (POAH) region, iloprost (2-50 ng/POAH) induced a biphasic
      increase in rectal temperature. While the first phase was inhibited by AH 6809,
      an E1-type prostaglandin (EP1) receptor antagonist, the second phase was
      abolished by indomethacin pretreatment. Iloprost was found not to alter rectal
      temperature when injected into the ventromedial hypothalamic area. Administration
      of iloprost into the POAH in a dose that had no effect on rectal temperature
      significantly potentiated the hyperthermic effect of PGE2 (50 ng, ICV). These
      findings suggest that the pyrogenic effect of iloprost is partly mediated by EP1
      receptors located on the POAH. Regarding the similarities of iloprost and PGI2,
      it is further proposed that endogenous PGI2 might act to modulate hyperthermic
      effect of PGE2 released during arachidonic acid- or endogenous pyrogen-induced
      fever.

PMID- 7505456
TI  - Direct evaluation of radiation damage in human hematopoietic progenitor cells in
      vivo.
AB  - We have developed techniques by which normal functional elements of human bone
      marrow can be implanted into immunodeficient C.B-17 scid/scid (SCID) mice.
      Afterward, long-term multilineage human hematopoiesis is sustained in vivo. We
      evaluated the effect of irradiation on the function of human bone marrow with
      this in vivo model. After whole-body X irradiation of the engrafted animals, it
      was determined that the D0 value of human committed progenitor cells within the
      human marrow was 1.00 +/- 0.09 (SEM) Gy for granulocyte-macrophage colony-forming
      units (CFU-GM) and 0.74 +/- 0.12 Gy for erythroid burst-forming units (BFU-E).
      The effects of irradiation on the hematopoietic elements were reduced when the
      radioprotective agent WR-2721 was administered prior to irradiation. After low
      dose irradiation, recovery of human myelopoiesis was accelerated by treatment
      with human granulocyte colony-stimulating factor (G-CSF). This small animal model
      may prove amenable for the analysis of the risk of the exposure of humans to
      radiation as well as for the development of new modalities for the prevention and
      treatment of radiation-induced hematopoietic damage.

PMID- 7505458
TI  - Insulin-like growth factor (IGF) binding proteins and insulin-like growth factor
      secretion by cultured chondrocyte cells: identification, characterization and
      ontogeny during cell differentiation.
AB  - Insulin-like growth factor binding proteins (IGF BP) and insulin-like growth
      factors (IGF) secretion by differentiating chondrocytes, derived from mouse
      embryonic limb bud and responsive to both IGF-I and -II [23], was investigated.
      The Western ligand blot analysis of the conditioned medium (CM) from days 1, 3, 5
      and 7 of culture revealed the secretion of IGF BP of approx. 35-40, 28-30 and 24
      26 kDa. The 35-40 kDa protein which comigrated with the 40 kDa protein in CM of
      trophoblast cells identified as IGF BP-3. The 28-30 kDa protein was identified as
      IGF BP-2 by Western immunoblotting with alpha-IGF BP-2 antisera. The 24-26 kDa
      protein was consistent with the nonglycosylated form of IGF BP-4. Secretion of
      three IGF BPs were increased with the age of the culture. This suggested that the
      major IGF BP secreted by differentiating chondrocytes in culture are IGF BP-2, -3
      and -4. All three of these IGF BPs were stimulated by both IGF-I and -II. IGF-I
      was approx. 2-fold more potent than IGF-II. The investigation of the localized
      production of IGF revealed that chondrocytes, similar to IGF BP, secreted IGF-II
      in differentiation dependent manner. No IGF-I secretion was identified.
      Examination of the secretion of solubilized IGF-II receptor by the chondrocytes,
      in contrast to trophoblasts, failed to reveal the presence of IGF-II receptor in
      the CM. This suggested that, unlike many other cells, including trophoblasts,
      chondrocytes do not secrete solubilized IGF-II receptor. In summary, the present
      results suggested an interactive autocrine/paracrine action of IGF BP and IGF-II
      in the chondrocytes, while the IGF-I action is predominantly endocrine.

PMID- 7505457
TI  - Binding sites for interferons on ovine and human endometrial membranes.
AB  - In the ewe, the major product of the preimplantation blastocyst is ovine
      trophoblast protein-1 (oTP-1), which is now classified as an omega-interferon
      (IFN). Receptors for IFN are present on sheep endometrium and vary cyclically,
      presumably modified by the actions of ovarian steroids. This study examined
      whether or not IFN receptors were present on human endometrium at any stage
      during the menstrual cycle. In addition, the steroid dependence of ovine
      endometrial IFN receptors was determined. Specific binding of 125I-labelled IFN
      (125I-IFN) to ovine endometrial membranes was substantially higher than binding
      to membranes derived from bovine spleen, human placenta or pooled human
      endometrium (relative specific binding 100:33:36:20). Human endometrial membrane
      preparations from proliferative-phase tissue showed very little specific binding
      (mean 0.8 +/- 0.3%, n = 4) in contrast to luteal-phase endometrium (2.1 +/- 0.3%,
      n = 8). Treatment of ovariectomized ewes with oestradiol-17 beta (E) resulted in
      significantly increased binding (117 +/- 7%) of 125I-IFN to endometrial tissues
      compared with tissue from ovariectomized (OvX, 75 +/- 7%), progesterone (P)
      treated (69 +/- 7%), or (E + P)-treated (81 +/- 8%) groups (P < 0.05); all were
      compared with binding to pooled ovine luteal-phase tissue, 100%. There were no
      differences between the other three groups. Scatchard analysis showed binding
      affinity of the same order for the sheep and human receptors (Kd = 10(-10) mol L
      1) but binding capacity was considerably lower for human (6.0 fmol mg-1) than for
      sheep (47-123 fmol mg-1) endometrium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505459
TI  - Expression of insulin-like growth factor binding protein-4 (IGFBP-4) by rat
      neural cells--comparison to other IGFBPs.
AB  - We recently isolated and characterized the 24 kDa and N-glycosylated 28 kDa
      insulin-like growth factor binding protein-4 (rIGFBP-4) from the B104s rat
      neuronal cell line (Endocrinology, 129 (1991) 1009-1115). To examine the
      prevalence of IGFBP-4 secretion by cells of neural origin, we assessed the
      expression of IGFBP-4 in different neural cell types using ligand blotting,
      immunoblotting and blot hybridization with relevant cDNAs. A specific IGFBP-4
      antibody raised against a synthetic 20 amino acid peptide was used for
      immunologic recognition. In all the neural cells tested (B104s, C6 astrocytoma,
      primary neonatal astrocytes and primary fetal neurons), IGFBP-4 was definitively
      identified by immunoblotting. Blot hybridization using a rat cDNA probe revealed
      expression of IGFBP-4 mRNA transcripts by all these cells. Using a combination of
      the same techniques, expression of IGFBP-1, -2, and -3 were also examined. The
      B104s cells secreted primarily IGFBP-4; C6 cells secreted predominantly IGFBP-3
      and small amount of IGFBP-4; both primary neonatal astrocytes and fetal neurons
      secreted IGFBP-2 as the major IGFBP accompanied by a small quantity of IGFBP-4.
      IGFBP-1 was not identified in any of the cell media. When probed with the
      respective IGFBP cDNAs, the mRNA abundance generally reflected the media IGFBP
      content. The expression of IGFBP-4 mRNA in vivo was examined as well and compared
      to that of IGFBP-1 and IGFBP-2. Transcripts for both IGFBP-2 and IGFBP-4 were
      found in all gross anatomical divisions of the rat brain from embryonic day 15
      until adulthood, whereas IGFBP-1 was not detected at any time. IGFBP-4 mRNA
      tended to be more abundant at the youngest ages whereas IGFBP-2 increased during
      development. These data indicate that IGFBP-4 is produce by a variety of neural
      cell types and suggest that it may play a role in brain development.

PMID- 7505460
TI  - Elimination of radiolabelled recombinant human insulin-like growth factor binding
      protein-3 from the circulation, and its distribution amongst organs and tissues
      in adult male rats.
AB  - Most insulin-like growth factor-I (IGF-I) in blood is found in complex with IGF
      binding protein-3 (IGFBP-3). An additional association of IGFBP-3 with an acid
      labile subunit is thought to severely limit its ability to cross the vascular
      endothelium. However, it is not clear whether IGFBP-3 which is not complexed to
      acid-labile subunit can gain access to tissues and contribute to the
      transcapillary transport of IGF-I. We have investigated the concentration time
      profile of 125I-labelled recombinant, non-glycosylated human IGFBP-3 in the rat
      circulation, its appearance within various organs, urine, and in peritoneal
      lavage fluid. Radiolabelled IGFBP-3 was administered as a single infusion over 1
      min into the catheterized jugular vein of male Wistar rats. Blood was sampled
      from the femoral artery, and urine by cannulation of the bladder for up to 3 h.
      The peritoneal cavity was cannulated to allow for the collection of lavage fluid.
      In a separate series of animals various organs were collected up to 3 h following
      administration of 125I-labelled IGFBP-3, and the content of radiolabel estimated
      by gamma spectrometry. Radiolabelled IGFBP-3 was rapidly cleared from the
      circulation initially (half-life 25 min), however from 70 min life to 3 h the
      levels of radiolabel remained constant. Neutral gel filtration on Sephadex G200
      revealed that 1 h following administration the majority of the [125I]IGFBP-3
      existed within a complex of 100-120 kDa, likely to represent an association with
      the acid-labile subunit. Radioactivity was detected in urine within 30 min of
      IGFBP-3 administration, was maximally present at 60 min, but declined thereafter.
      A proportion of the radiolabel in urine represented degraded protein fragments of
      IGFBP-3, although only 8% of the administered radiolabel was excreted within
      urine over 3 h. Within 10 min of entry into blood 125I-labelled IGFBP-3 was found
      within peritoneal lavage fluid. Most of the radiolabel was accumulated within the
      kidneys, liver, stomach and intestine up to 3 h after administration. However,
      while the hepatic and renal content were maximal after 30 min, stomach content
      continued to rise over 1 h, and stabilized at 15% of administered dose for up to
      3 h. The results suggest that when not in complex with the acid-labile subunit,
      IGFBP-3 can rapidly cross capillary endothelia from blood to extravascular
      compartments. While kidney and liver are likely sites of excretion and
      degradation, a substantial proportion of IGFBP-3 is also accumulated by
      gastrointestinal tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7505461
TI  - Developmental regulation of insulin-like growth factor binding protein-2 in chick
      embryo serum and vitreous humor.
AB  - The chick embryo is a useful vertebrate model for studying developmental
      embryogenesis. Insulin-like growth factor I (IGF-I), a potent mitogen, is thought
      to contribute to the general growth of the embryo as an endocrine factor, and as
      a paracrine factor to the development of the early embryo and of specific organs
      such as the eye. Recent data suggest that a family of at least six IGF binding
      proteins (IGFBPs) complex IGF-I and modulate its biological actions. In the
      present study, we examine the expression of IGFBPs in chicken serum and vitreous
      humor at different stages of embryonic development, and compare it with that of
      IGF-I. As determined by ligand blotting, the predominant IGFBP in chick serum and
      vitreous humor between embryonic days 4 and 22 (E4-E22) is a 30 kDa IGFBP. This
      IGFBP was specifically immunoprecipitated by a polyclonal antiserum raised
      against rat IGFBP-2, the predominant IGFBP in fetal human and rat serum. Although
      IGFBP-2 is present in both chick fluids at all times examined, serum IGFBP-2
      increased progressively between E10-E22, whereas vitreous IGFBP-2 was highest
      during eye organogenesis (E4-E8). This suggests that vitreous IGFBP-2 is
      synthesized locally. Like serum IGFBP-2, levels of immunoreactive IGF-I in serum
      are higher in the second week of embryogenesis than the first. Despite this
      correlation, changes in IGFBP-2 do not appear to be regulated by IGF-I: (a) serum
      IGF-I decreases after day 15, whereas IGFBP-2 levels remain stable until
      hatching; (b) vitreous IGF-I, like serum IGF-I, is higher in the second week of
      embryogenesis, whereas vitreous IGFBP-2 is highest in the first week; (c) embryos
      cultured ex ovo express IGFBP-2 at E15-E19, although they lack the normal mid
      embryogenesis surge in IGF-I. We conclude that vitreous IGFBP-2 is synthesized
      locally in the eye, and that the expression of IGFBP-2 in chick embryos is not
      directly regulated by IGF-I.

PMID- 7505462
TI  - Insulin-like growth factor binding protein-2, 28 kDa and 24 kDa insulin-like
      growth factor binding protein levels are decreased in fluid of dominant
      follicles, obtained from normal and polycystic ovaries.
AB  - In order to investigate potential changes in insulin-like growth factor binding
      proteins (IGFBPs) during human follicle maturation, we examined the IGFBP
      profiles in follicular fluid from follicles in different stages of maturation.
      Samples were obtained from ovaries of women with regular menstrual cycles and of
      subjects with cycle abnormalities and polycystic ovaries (diagnosed as polycystic
      ovary syndrome (PCOS)) and analyzed by Western ligand blotting. IGFBPs of 43 kDa,
      37 kDa, 31 kDa, a doublet around 28 kDa and a minor band of 24 kDa were detected
      in follicle fluid of normal non-dominant (size < 10 mm) and atretic
      (androstenedione/estradiol ratio > 4) follicles of both regularly menstruating
      women and PCOS patients. The 43 and 37 kDa IGFBPs could be identified as IGFBP-3
      and the 31 kDa IGFBP as IGFBP-2, whereas the 28 kDa IGFBP could not be identified
      as IGFBP-1, all by immunoblotting techniques. A dramatic decrease in IGFBP-2, the
      28 kDa and 24 kDa IGFBPs was observed in follicular fluid of dominant follicles
      (size > 10 mm) of both regular menstruating individuals and one PCOS patient as
      compared with follicular fluid of normal non-dominant or atretic follicles. These
      observations indicate that the PCOS follicle may not be different from normal
      with respect to IGFBP profiles. Furthermore, these results suggest that at least
      one of these IGFBPs might be involved in human folliculogenesis.

PMID- 7505464
TI  - Evidence that limited proteolysis of insulin-like growth factor binding protein-3
      (IGFBP-3) occurs in the normal state outside of the bloodstream.
AB  - In serum and other biological fluids, IGF-I and IGF-II are reversibly bound to
      six molecular species of specific binding proteins (IGFBP-1 to -6) which regulate
      their transport to target cells as well as their biological activities. Most of
      the IGFs in adult serum are bound to IGFBP-3 and associated with a 85 kDa subunit
      to form 150 kDa ternary complexes, very few of which cross the capillary barrier.
      In earlier studies we showed that during pregnancy one or more serine proteinases
      are responsible for limited proteolysis of IGFBP-3 in the serum. This may result
      in easier dissociation of the IGFs and hence an increase in their availability.
      In the present work, the results of Western blot analyses of the IGFBPs, using
      either labelled IGF or a polyclonal anti-IGFBP-3 antibody, have demonstrated that
      IGFBP-3 proteolysis occurs in the normal state. In all the adults investigated,
      serum contained both the 42-39 kDa doublet, characteristic of intact IGFBP-3, and
      its major degradation fragment of 30 kDa. The fragment was also found in lymph,
      in addition to smaller fragments of 21.5, 20 and 16 kDa which are the same sizes
      as those seen in pregnancy serum. Comparisons of lymph (which reflects the
      interstitium) and serum from the same subjects showed greater proportions of
      IGFBP-3 proteolysed in lymph than in serum and incubations with [125I]IGFBP-3
      showed almost 8-fold higher proteolytic activity in lymph than in serum where it
      was minimal. These findings suggest that the initial sites of proteolysis are in
      the tissues. Like that in pregnancy serum, the activity was calcium-dependent and
      inhibited by aprotinin. The results of this study fit the hypothesis that limited
      proteolysis of IGFBP-3 may be an essential mechanism in controlling the
      bioavailability of the IGFs, both at the cellular level and, in the blood, from
      the 150 kDa complexes which constitute the circulating reserves of IGF.

PMID- 7505463
TI  - Insulin-like growth factor regulation of human endometrial stromal cell function:
      coordinate effects on insulin-like growth factor binding protein-1, cell
      proliferation and prolactin secretion.
AB  - The insulin-like growth factor (IGF) autocrine/paracrine system is believed to be
      involved in endometrial differentiation, but there is limited information on the
      specific cellular functions regulated by IGFs in uterine tissues and their
      regulation of IGF-binding proteins (IGFBPs). We have investigated the regulation
      by insulin, IGF-I, and IGF-II, of IGFBP secretion in human endometrial stromal
      cells decidualized in vitro, and examined the interrelationship between the
      induced changes in IGFBP levels and the biological responses of stromal cells to
      IGFs. IGFBPs in conditioned media were analyzed by Western ligand blotting, and
      IGFBP-1 was quantified by an immunoenzymometric assay (IEMA). In the absence of
      peptides, decidualized stromal cells secreted 25.5 +/- 3.2 micrograms/day per
      10(6) cells of IGFBP-1. Insulin caused a dose-dependent reduction of IGFBP-1
      secretion (half-maximal inhibition at < 1 ng/ml) to a maximum of 1% of control
      values. Northern analysis using a specific cDNA probe showed the expression in
      decidualized stromal cells of a single 1.5 kb transcript for IGFBP-1, which was
      absent in insulin-treated cells. The effects of IGF-I and IGF-II on IGFBP-1
      secretion were biphasic, with initial stimulation (200-250%) that peaked at 1 and
      10 ng/ml, respectively, followed by inhibition at higher concentrations (half
      maximal inhibition at 3 ng/ml and 30 ng/ml, respectively). The decrease in IGFBP
      1 levels in decidualized stromal cultures was associated with the induction of
      mitogenesis by IGF-I and IGF-II, while IGF effects on prolactin secretion
      paralleled those of IGFBP-1 secretion, with stimulation (243-324%) in the low
      concentration range followed by inhibition at higher concentrations. These data
      indicate that endometrial stromal cell IGFBP-1 is regulated by insulin, at
      concentrations that are compatible with insulin acting via its own receptor,
      while the effects of IGF-I and IGF-II on IGFBP-1 secretion, are suggestive of
      their acting probably through the type I IGF receptor. The present study
      describes distinct effects of the IGFs on stromal cell IGFBPs, that correlate
      with changes in the proliferative and secretory responses of decidualized stromal
      cells to the IGFs. Our findings suggest that complex IGF-IGFBP interactions may
      participate in the regulation of endometrial cell function, and support a role
      for IGF-II in stromal cell mitogenesis during decidualization, and as a local
      regulator of decidual cell function during the late secretory phase and early
      pregnancy.

PMID- 7505465
TI  - Tissue-specific expression of the insulin-like growth factor binding protein
      (IGFBP) mRNAs in mouse and rat development.
AB  - The insulin-like growth factor binding proteins (IGFBPs) are polypeptides which
      are thought to modulate the bioactivity of IGF-I and IGF-II, and may also have
      activities independent of the IGFs. The expression patterns of IGFBPs-1, -3, -4,
      and -6 in midgestational rodents were analyzed using in situ hybridization to
      begin to characterize the role of these IGFBPs during development. All IGFBPs are
      expressed at least as early as rat embryonic day 14 (e14), and each has a unique
      pattern of expression. IGFBP-1 mRNA is expressed by the liver throughout mid and
      late gestation. IGFBP-3 mRNA is expressed at high levels in the urogenital tract,
      several muscle groups, and the nasal epithelia. IGFBP-3 transcripts are also
      expressed at lower levels by many non-neural tissue types, including the liver,
      stomach, and heart. IGFBP-4 is abundantly expressed by many tissues in the
      developing embryo, with the notable exceptions of the spinal cord, specific
      cartilage groups, and the thymic cortex. IGFBP-6 is expressed in the liver by
      e14, and also by a previously unrecognized cell population surrounding developing
      cartilage. Taken together these observations suggest distinct roles in
      development for each of the IGFBPs.

PMID- 7505466
TI  - Insulin-like growth factor (IGF) suppression of IGFBP-1 production: evidence for
      mediation by the type I IGF receptor.
AB  - The regulation of insulin-like growth factor binding protein-1 (IGFBP-1) by its
      ligands, IGF-I and IGF-II, was studied in continuous cultures of HepG2 human
      hepatoma cells. Both IGF-I and IGF-II in concentrations as low as 1-10 nmol/l
      caused significant suppression of IGFBP-I protein levels. This suppression was
      accompanied by decreased IGFBP-1 mRNA levels occurring within 2-4 h of exposure
      to IGF-I or IGF-II, and by a significant decrease in IGFBP-1 promoter activity.
      IGF-I and IGF-II were equipotent in suppressing basal levels of IGFBP-1 protein,
      mRNA and promoter activity. IGF-I, IGF-II, and IGF-analogs with low IGFBP-1
      affinity, (des 1-3)IGF-I and long R3IGF-I, all potently suppressed the previously
      characterized increase in IGFBP-1 protein levels and promoter activity induced by
      cAMP and theophylline. In contrast, [Leu-27]IGF-II, which interacts with the type
      II but not type I IGF receptor, had no effect on IGFBP-1 protein levels or
      promoter activity. Our data indicate that IGFBP-1 production is inhibited by its
      ligands, IGF-I and IGF-II, and that this effect is probably mediated at the
      transcriptional level. The effects of IGF-I and IGF-II apparently occur as a
      result of binding to the type I IGF receptor, and are similar to the previously
      characterized suppressive effects of insulin on IGFBP-1 transcription mediated
      through the insulin receptor. When considered with previous data regarding
      expression of IGFBP-1 and the type I IGF receptor, our results suggest that IGF
      regulation of IGFBP-1 may play an as yet undefined role in fetal development and
      postnatal hepatic regeneration.

PMID- 7505467
TI  - Insulin-like growth factor-I (IGF-I) dependent phosphorylation of the IGF-I
      receptor in MG-63 cells.
AB  - Insulin-like growth factor I (IGF-I) stimulates multiplication of the human
      osteosarcoma cell line, MG-63. by acting through the IGF-I receptor. We have
      characterized IGF-I stimulated phosphorylation of the IGF-I receptor in this cell
      line. Serum starved MG-63 cells were metabolically labeled with
      [32P]orthophosphoric acid and the cells were treated with IGF-I. Phosphotyrosine
      containing proteins were immunoprecipitated from the cell lysates with
      antiphosphotyrosine-Agarose and eluted with phenyl phosphate. Further
      immunoprecipitation with IGF-I receptor monoclonal antibodies (alpha IR-3, 18E9)
      and analysis by sodium dodecylsulfate polyacrylamide gel electrophoresis and
      autoradiography demonstrated IGF-I dependent autophosphorylation of the IGF-I
      receptor. Phosphoamino acid analysis of the IGF-I receptor beta subunit and the
      observation that antiphosphotyrosine-Agarose did not immunoprecipitate
      [35S]methionine-labeled receptor from unstimulated cells, demonstrated that in
      the absence of IGF-I, the receptor was not phosphorylated on tyrosine residues.
      Western blotting of cell lysates with a monoclonal phosphotyrosine antibody did
      not identify the IGF-I receptor or pp185 but demonstrated IGF-I dependent
      phosphorylation on tyrosine residues in three other proteins, p110, p70 and p40.

PMID- 7505468
TI  - Immunocytochemical detection of insulin receptor substrate-1 (IRS-1) in rat
      brain: colocalization with phosphotyrosine.
AB  - In peripheral insulin-sensitive tissues, insulin receptor substrate (IRS-1)
      undergoes tyrosine phosphorylation immediately after cells are stimulated by
      insulin or insulin-like growth factor-1 (IGF-1), and may function as a molecular
      link between insulin/IGF-1 receptor tyrosine kinases and enzymes regulating cell
      growth and metabolism. A fundamental question pertaining to insulin/IGF-1 action
      in the brain is whether IRS-1 is expressed by neurons. In this study, the
      distribution of cells containing immunoreactivity to IRS-1 in the brain was
      determined by immunocytochemistry with polyclonal IRS-1 antiserum, and compared
      to the localization of immunostaining for phosphotyrosine using polyclonal
      phosphotyrosine antiserum. The immunostaining results with ABC-peroxidase method
      and cryostat sections showed the presence of IRS-1 immunoreactivity in many
      neuron cell bodies throughout the rat forebrain, particularly in the habenula,
      cerebral cortex and piriform cortex. In the hypothalamus, IRS-1 immunostaining
      was present in neurons of the paraventricular nucleus, supraoptic nucleus, and
      arcuate nucleus. The choroid plexus stained intensely for IRS-1. The populations
      of cells that stained for IRS-1 also showed strong immunostaining for
      phosphotyrosine. Studies at the cellular level are needed to verify coexpression
      of IRS-1 and receptors for insulin or IGF-1 by the same neurons, as well as in
      cells of the choroid plexus. The present results are the first demonstration of
      IRS-1 expression by neurons in adult mammalian brain. These findings are
      consistent with the hypothesis that insulin and IGF-1 actions in the brain
      involve signal transduction mechanisms common to those found in peripheral
      tissues.

PMID- 7505469
TI  - Inhibition of IGF-I and b-FGF stimulated growth of human retinal endothelial
      cells by the somatostatin analogue, octreotide: a potential treatment for ocular
      neovascularization.

PMID- 7505470
TI  - Circulating levels of IGFs and IGF binding proteins in human cord serum:
      relationships to intrauterine growth.
AB  - Cord sera were obtained from 44 term, human infants exhibiting various patterns
      of intrauterine growth and were assayed for IGF-1, IGF-2, and IGFBP-1, 2, and 3
      by specific RIAs. Serum levels were correlated with birth weight (BW), ponderal
      index (PI), and placental weight (PW). Total IGF-1 levels correlated
      significantly with BW (r = 0.392), PW (r = 0.351), and PI (r = 0.481). By
      contrast, the correlation of IGF-2 with birth weight was not statistically
      significant (r = 0.264, P = 0.091). The association of IGF-2 with PI, however,
      was significant (r = 3.348, P = 0.024). IGFBP-3 exhibited significant
      correlations with BW, PI, and PW, similar to those seen with IGF-1. IGFBP-1 and
      IGFBP-2, however, were not significantly related to growth parameters. IGF-1
      levels correlated strongly with IGFBP-3 levels (r = 0.646, P = 0.001). By
      contrast, IGF-1 correlated with the reciprocal of both IGFBP-1 and IGFBP-2. Based
      upon in vitro affinity constants, theoretical concentrations for each [IGF/IGFBP]
      complex, free IGFs, and free IGFBPs were calculated for each infant. Multiple
      regression analysis was performed including all 11 calculated variables and
      correlated with each growth parameter. This analysis revealed that an integrated
      expression of IGF activity exhibited stronger correlations with growth than each
      individual peptide species (BW, r = 0.681; PI, r = 0.660; PW, r = 0.658). These
      data further support roles for IGF related peptides (IGFRPs) in human fetal and
      placental growth and suggest regulatory/counterregulatory roles for the IGFBPs.
      It also supports the hypothesis that individual IGFRPs interact in a complex
      manner to define 'net IGF activity' in relation to fetal growth and/or metabolic
      status.

PMID- 7505471
TI  - Alterations in the synthesis of insulin-like growth factor binding proteins and
      insulin-like growth factors in rat C6 glioma cells transfected with a gap
      junction connexin43 cDNA.
AB  - When C6 glioma cells are stably transfected with a connexin43 cDNA and gap
      junctions are increased, the rate of cellular proliferation is decreased. To
      determine if this phenomenon is related to alterations in IGFBP and IGF
      synthesis, we have compared IGFBPs and IGFs in the conditioned media from primary
      rat astroglia, C6, and transfected C6 clones Cx43-13 (high expresser), and Cx43
      12 and Cx43-14 (intermediate expressers). Primary astroglia produced IGFBP-2 (34
      kDa) and IGFBP-3 (40-45 kDa). C6 cells synthesized high levels of IGFBP-3 and low
      levels of IGFBP-2, and a 24 kDa IGFBP (IGFBP-4). Cx43-13 cells did not synthesize
      IGFBP-3, but produced low levels of IGFBP-2 and high levels of IGFBP-4. Cx43-12
      and Cx43-14 secreted IGFBP profiles similar to the parent C6 line, but with
      reduced levels of IGFBP-2. The lack of IGFBP-3 in Cx43-13 cells was not due to
      the presence of proteases. Northern analysis showed IGFBP-2 mRNA to be readily
      detectable only in the primary astroglia. IGFBP-3 mRNA was detected in the
      primary astroglia, C6, Cx43-12 and Cx43-14, but not in Cx43-13. In contrast,
      IGFBP-4 mRNA was readily detected only in the Cx43-13. IGF-II concentrations in
      the media were low to undetectable for both C6 and transfected cells. IGF-I
      concentrations were significantly lower in the media from transfected cells
      compared to the C6 cells. Stable mRNA levels for IGF-I were lower in transfected
      cells, with the lowest levels observed in the Cx43-13 cells. Although C6 cells
      did not respond mitogenically to exogenous IGF-I or IGF-II, Cx43-13 cells
      responded to IGF-I or IGF-II in a dose dependent manner. Conditioned media from
      Cx43-13 cells decreased the DNA synthesis of C6 cells, and this effect could be
      reversed by the addition of IGF-II. The decreased synthesis of the
      autocrine/paracrine growth factor IGF-I together with decreased levels of a
      positive modulator IGFBP-3, and the increased levels of a negative modulator
      IGFBP-4 in the extracellular milieu, may be responsible for the reduced
      proliferative capacity in cells expressing abundant connexin43.

PMID- 7505472
TI  - Observations on the effects of hematopoietic colony-stimulating factors on the
      clinical course of bone marrow transplantation.

PMID- 7505473
TI  - [Treatment of benign prostatic hypertrophy].

PMID- 7505474
TI  - [Prostatic surgery. Preoperative and postoperative care].

PMID- 7505475
TI  - [Prostatic adenoma or benign prostatic hypertrophy].

PMID- 7505476
TI  - [Benign prostatic hypertrophy. Contribution of complementary examinations].

PMID- 7505477
TI  - [Hepatitis C: from pathogenesis to treatment].
AB  - Hepatitis C virus (HCV) belongs to the greater family of Flaviviridae. It is
      probably responsible for the majority of NANB hepatitis. Serologic evidence in
      the term of antibodies against certain parts of HCV persists in 60 to 100% of
      patients with NANB hepatitis after blood transfusion. The evidence for the
      existence of a second virus responsible for NANB has not been excluded as
      inactivation-studies would suggest. HCV is also a common cause for sporadic acute
      hepatitis. It is the purpose of this article to present diagnosis, course and
      treatment of this form of hepatitis.

PMID- 7505478
TI  - The reference range for complexed alpha 2-macroglobulin human plasma: development
      of a new enzyme linked in immunosorbent assay (ELISA) for quantitation of
      complexed alpha 2-macroglobulin.
AB  - Purified alpha 2-macroglobulin was complexed by reaction with methylamine and
      used to raise monoclonal murine antibodies. A four-step enzyme linked
      immunosorbent assay (ELISA) was developed to determine the antibody-specificity
      of the produced monoclonal murine antibodies towards human native and complexed
      alpha 2-macroglobulin. Two monoclonal antibodies were selected, H11A11 (specific
      towards complexed alpha 2-macroglobulin) and 1CG4 (recognizes both forms of the
      molecule), and purified by affinity chromatography on protein G. The purified
      antibodies were used to develop a fast three-step ELISA for exact quantitation of
      complexed and total alpha 2-macroglobulin in human plasma. The intra-assay
      coefficient of variation (CV) for measurement of complexed alpha 2-macroglobulin
      is 2.2-9.9%, whereas the inter-assay CV was determined to be 3.7-10.5% and the
      recovery of the assay is 93-108%. The assay for total alpha 2-macroglobulin has
      an intra-assay CV of 3.0-15.5%, an interassay CV of 5.1-21.2% and a recovery of
      91-116%. Citrated plasma samples from 139 healthy blood donors were examined,
      resulting in a reference range for complexed alpha 2-macroglobulin of 13.5-31.1
      mg 1(-1) with a median value of 21.7 mg 1(-1). The concentration of total alpha 2
      macroglobulin was measured by the same assay using the monoclonal antibodies
      1CG4. For total alpha 2-macroglobulin we determined the reference range to be
      1.12-3.54 g 1(-1) with a median value of 2.14 g 1(-1). Based on these results the
      reference range for complexed alpha 2-macroglobulin as a percentage of total
      alpha 2-macroglobulin was calculated to be 0.8-1.9% with a median value of 1.0%.

PMID- 7505479
TI  - Growth-regulatory effects of sensory neuropeptides, epidermal growth factor,
      insulin, and somatostatin on the non-transformed intestinal epithelial cell line
      IEC-6 and the colon cancer cell line HT 29.
AB  - A non-transformed small-intestinal cell line from the rat (IEC-6) and a human
      colon cancer cell line (HT 29) were examined for their trophic response to
      sensory neuropeptides. Substance P, neurokinin A (NKA), calcitonin gene-related
      peptide (CGRP), vasoactive intestinal peptide (VIP), and peptide YY (PYY) were
      tested. Epidermal growth factor (EGF), insulin, and somatostatin-14 were also
      used. Interaction studies were performed on IEC-6 cells by combining EGF or
      insulin with somatostatin-14. The sensory neuropeptides had no effect either on
      IEC-6 cell growth and DNA synthesis or on HT29 cell growth. EGF and insulin
      stimulated cell growth and DNA synthesis in IEC-6 cells and cell growth in HT 29
      cells in a dose-dependent fashion. Somatostatin-14 had no effect either alone or
      in combination with EGF or insulin on IEC-6 cell growth and DNA synthesis. HT 29
      cell growth was inhibited by somatostatin-14 only in the presence of serum with a
      maximal and significant response at 10(-7) M. Our observations suggest that the
      sensory neuropeptides do not exert a direct growth-regulatory effect either on
      IEC-6 cells or on HT 29 cells. Somatostatin, however, inhibits serum-induced HT
      29 cell growth but does not interfere directly with the proliferative effect of
      serum, EGF, or insulin on IEC-6 cells in this model.

PMID- 7505480
TI  - Prospect for an additional laboratory criterion for rheumatoid arthritis.
AB  - The aim of the study was to establish the benefit of an additional hypothetical
      laboratory criterion for rheumatoid arthritis (RA), comprising positivity for
      antikeratin antibody (AKA) and/or antiperinuclear factor (APF). The tests were
      applied to a series of 308 hospital patients with various recent-onset
      inflammatory joint diseases who were followed for 3 years. The performance of APF
      and AKA was compared with rheumatoid factor (RF). The most sensitive (.72) but
      the least specific (.86) test for RA was the latex test. The most specific (.96)
      but the least sensitive (.33) test was AKA. Waaler-Rose and APF were
      intermediate. AKA and/or APF positive patients had significantly more erosions
      than patients negative for these autoantibodies. Despite the impressive
      performance characteristics of APF and AKA, the actual classification impact
      achieved, as compared to using RF as the sole laboratory criterion, turned out to
      be moderate. This is because the criteria proved to be interrelated. Unlike RF,
      AKA and APF are not suited to the general laboratory, at least not in their
      present form. Moreover they so far lack the broad data base of RF.

PMID- 7505481
TI  - Changes in levels of IgM RF and alpha 2 PAG correlate with increased disease
      activity in rheumatoid arthritis during the puerperium.
AB  - In this prospective study of 24 pregnant patients with rheumatoid arthritis,
      quiescent disease activity in 21 patients (88%) during gestation was followed by
      more active disease in the puerperium in 19 patients (79%). Increased disease
      activity was reflected in a deterioration in manual dexterity and this was found
      to correlate with a post-partum rise in IgM rheumatoid factor (IgM RF) (r = 0.86)
      and a post-partum decline in pregnancy associated alpha-2 glycoprotein (PAG) (r =
      0.44). The increase in IgM RF also correlated with increased disease activity
      measured by a visual analogue scale (r = 0.44). Changes in IgA RF were not
      observed. These results suggest that PAG and IgM RF could contribute to the
      modulation and pathogenesis of rheumatoid arthritis during pregnancy.

PMID- 7505482
TI  - Autocrine and paracrine growth loops in chronic lymphocytic leukemia.

PMID- 7505483
TI  - Expression and function of adhesion receptors on normal B cells and B cell non
      Hodgkin's lymphomas.
AB  - A large number of molecules have been identified and characterized which mediate
      (1) homing of lymphoid cells to lymphoid tissues; (2) localization of cells
      within distinct microenvironments; and (3) cell-cell and cell-matrix interactions
      within those microenvironments. B lymphocytes express these adhesion receptors
      during stages of normal ontogeny. Malignant B cells can also express these
      adhesion molecules, and they probably serve a "normal" function in a neoplastic
      state. However, the aberrant expression and/or function of adhesion receptors may
      in part explain the clinical and biological behavior of these diseases. Further
      insight into the normal function of these surface molecules may provide novel
      approaches with which to consider the regulation of growth and dissemination of
      these cells in vivo, thereby suggesting new therapeutic approaches.

PMID- 7505484
TI  - Five year survival following surgery for 50 cases of colorectal cancer--a
      personal series.
AB  - In a personal series of 56 patients with colorectal cancer operated over a 3-year
      period from 1984 to 1986, 50 patients were followed up until death or for at
      least 5 years. The age, distribution, clinical features and stage of disease at
      presentation appear to be similar to those in the West. All 5 of Dukes A, 10 of
      11 cases of Dukes B and 8 of 16 cases of Dukes C disease have survived at least 5
      years. The 5-year survivors include a patient who had undergone right hepatectomy
      for a large liver metastasis. The 5-year survival in this small personal series
      appears encouraging.

PMID- 7505485
TI  - Prevalence of markers of hepatitis viruses A, B, C and of HIV in healthy
      individuals and patients of a Cambodian province.
AB  - So far little was known on the epidemiology of hepatitis A, B, C and of AIDS in
      Cambodia and especially not in the rural area of Takeo. Therefore serological
      markers for past or ongoing infections with the disease causing viruses were
      measured in 559 healthy individuals (305 adults, 200 children and 54 mothers of
      children with liver disorders) and in 185 individuals (103 adults and 82
      children) with liver or kidney diseases. In none of the 744 samples tested was
      anti-HIV detected. 10-37% of the children and 73% of the adults showed HBV
      markers, HBsAg being detectable in 2-14% of the children and in 8% of the adults.
      The prevalence for anti-HCV was 6.5% in the adults with a predilection in males
      (9%). No markers for HCV infections were found in children. Growing, age related
      proportions of children (27-97%) and 100% of the adults were anti-HAV IgG
      positive. HBsAg was detected in 46% of the adults with acute hepatitis, in 45% of
      those with chronic hepatitis/liver cirrhosis and in 90% of patients with hepato
      cellular carcinoma (HCC). In children the corresponding figures were 18% for
      acute hepatitis and 18% for chronic hepatitis. Patients with acute hepatitis or
      HCC had a similar prevalence of anti-HCV as healthy individuals. However, 34% of
      the adult patients with chronic hepatitis/cirrhosis showed signs of a HCV
      infection. When the data were analysed with respect to modes of viral
      transmission, crowding, transmission by unsafe sexual practice or contaminated
      injection material, and to a lesser extent vertical transmission, seem to be
      relevant for HBV. The main mode of acquiring HCV infection is probably through
      medical injections of all sorts, a habit which is very popular in Takeo.
      Prophylactic measures should concentrate on the prevention of HBV and HCV
      infections by hygienic means. HBV mass vaccination should be considered in the
      future.

PMID- 7505486
TI  - Mapping of functional epitopes of Japanese encephalitis virus using monoclonal
      antibodies.
AB  - Epitopes involved in the important functions, hemagglutination (HA) and
      neutralization (NT), were mapped on Japanese encephalitis (JE) virus proteins by
      using monoclonal antibodies (MAbs). Fourteen MAbs raised against Nakayama-Yoken
      strain of JE virus characterized by hemagglutination inhibition (HI) and plaque
      reduction neutralization test (PRNT) were used to map the epitopes on the JE
      proteins by Western blot analysis in which non-reducing conditions were used for
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). With these
      MAbs, at least 8 functional epitopes were demonstrated comprising (i) epitopes
      recognized by 5 MAbs which gave strong HI but weak NT activities and were mapped
      on the envelope (E) 53 kDa protein; (ii) epitopes recognized by 2 MAbs which
      showed weak HI but strong NT activities and were mapped also on the E protein;
      (iii) epitopes recognized by 2 MAbs which possessed weak HI but no NT activities
      and were mapped on the E protein; (iv) an epitope recognized by 1 MAb which gave
      weak NT and no HI activities and was mapped on the nonstructural protein 5 (NS5);
      (v) an epitope recognized by 1 MAb which showed activities similar to (i) but was
      mapped on both E and NS5; (vi) an epitope recognized by 1 MAb which had high
      activities to both HI and NT and was mapped on E and NS5; (vii and viii) epitopes
      recognized by 1 MAb which also gave low HI but high NT, and strong HI as well as
      strong NT activities respectively, but their location could not be demonstrated
      by SDS-PAGE under non-reducing condition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505487
TI  - Hyskon-induced pulmonary edema.
AB  - Hyskon (32 percent dextran-70) (Hyskon Division, Pharmacia) is used during
      hysteroscopy to help visualization of the uterine surfaces. Pulmonary edema of an
      uncertain cause has occurred in many patients. Because this study could not be
      conducted in humans, we determined if Hyskon caused cardiogenic or non
      cardiogenic pulmonary edema in a dog model. Dogs were randomly assigned to
      receive an infusion of Hyskon or whole blood to sustain left ventricular end
      diastolic pressure between 20 and 23 millimeters of mercury for 60 minutes. In
      dogs receiving blood, there was no protein in the bronchoalveolar lavage before
      or after blood was given. In the Hyskon group, there was no protein in the
      bronchoalveolar lavage before Hyskon and 0.6 +/- 1.4 milligrams per deciliter
      (range of 0.1 to 3.7 milligram per deciliter) after Hyskon. The ratio of
      bronchoalveolar lavage protein to plasma protein after Hyskon was 8.0 +/- 18.0
      percent compared with zero percent in the blood group. Hyskon altered pulmonary
      microvascular membrane permeability, causing alveolar flooding with plasma
      proteins and possibly accounting for the deterioration of oxygenation and
      pulmonary compliance seen in patients. These results suggest a significant
      noncardiogenic component of Hyskon induced pulmonary edema.

PMID- 7505488
TI  - [New treatment of prostatic hyperplasia--but is it better?].

PMID- 7505489
TI  - The effect of alpha-latrotoxin on a synaptic connection between identified
      neurons in the brain of the mollusc Helix pomatia L.
AB  - The effect of alpha-latrotoxin on identified monosynaptic peptidergic contacts
      between identified neurons from the brain of the snail Helix pomatia L. was
      studied. It was found that, after extracellular application, toxin evoked an
      increase in the amplitude of the postsynaptic response. Neither amplitude nor
      duration of the action potential in a presynaptic neuron was affected.
      Intracellular injection of toxin into the soma of a presynaptic neuron led to a
      decrease in the postsynaptic current amplitude. The current induced by
      intracellular injection of cAMP into a postsynaptic neuron was also inhibited by
      extracellular or intracellular application of toxin. These data indicate that
      toxin evokes both an increase of transmitter release from a presynaptic neuron
      and a decrease in amplitude of the postsynaptic response.

PMID- 7505490
TI  - Immunochemical cross-reactivity of neurotoxic phospholipase A2 enzymes from
      Indian cobra (Naja naja naja) venom using polyclonal antibodies.
AB  - Rabbit antibodies were prepared against purified phospholipase A2 (NN-XIa-PLA2)
      from Indian cobra (Naja naja naja) venom. The PLA2 has haemolytic, neurotoxic,
      myotoxic, cytotoxic and oedema-inducing activities apart from the catalytic
      activity. The immunological cross-reactivity of structurally similar neurotoxic
      PLA2s was investigated using enzyme-linked immunosorbent assay (ELISA) and
      immunodiffusion. Anti-NN-XIa-PLA2 IgG cross-reacted with other purified
      neurotoxic PLA2s from the same venom. Immunochemical cross-reactions of anti-NN
      XIa-PLA2 IgG with NN-XIa-PLA2, NN-XIb-PLA2, NN-XIII-PLA2, NN-IVb1-PLA2 and NN-Vb
      PLA2 were shown by a very high ELISA titre and a single precipitin band on double
      immunodiffusion agarose plates. The catalytic activity of these PLA2s was
      inhibited dose-dependently by anti-NN-XIa-PLA2 IgG but was unable to neutralize
      lethality and neurotoxic symptoms in experimental animals injected with
      neurotoxic PLA2. Anti-NN-XIa-PLA2 IgG fails to neutralize myotoxicity and oedema
      inducing activities of NN-XIa-PLA2 and NN-XIII-PLA2. Anti-NN-XIa-PLA2 IgG
      inhibited cytotoxic effects of NN-XIa-PLA2 dose-dependently, but failed to
      inhibit NN-XIII-PLA2-induced cytotoxicity. Direct haemolytic activity of NN-XIa
      PLA2 and NN-XIII-PLA2 was inhibited dose-dependently by these antibodies. The
      results indicate the presence of separate catalytic and pharmacologic site(s).

PMID- 7505491
TI  - Cross-reactivities of monoclonal antibodies to a myotoxin from the venom of the
      broad-banded copperhead (Agkistrodon contortrix laticinctus).
AB  - A panel of murine monoclonal antibodies (MAbs) specific for a 14,500 mol. wt
      myotoxin of Agkistrodon contortrix laticinctus (broad-banded copperhead) venom
      was produced by cell fusion using the purified toxin as immunogen. The MAbs were
      used in immunoblotting and ELISA experiments to determine their immunological
      cross-reactivities. The three MAbs used in this study showed different
      immunoblotting and ELISA patterns when they were tested against 43 related and
      unrelated venom samples, indicating that they are specific for three different
      epitopes. MAb-42a specifically reacted with 50% of Agkistrodon venoms tested
      without cross-reacting with venoms of closely related species. This MAb reacted
      with venoms collected from Agkistrodon specimens from Florida, Kansas and Texas,
      but did not react with those from Louisiana, South Carolina, Ohio, New York or
      Mexico. MAb-6a showed similar reactivity but did react with venoms of snakes from
      Mexico. These results clearly indicate a geographical variation of the epitopes
      present in the myotoxin. Another antibody, MAb-18a, recognized an epitope present
      in the 14,500 mol. wt protein of all Agkistrodon venoms tested, but also reacted
      weakly with non-14,500 proteins from some Crotalus and Bothrops venoms tested.
      Both MAb-6a and MAb-18a neutralized the toxin-induced myonecrosis, but MAb-42a
      did not. Based on these results, the 14,500 mol. wt protein could serve as a
      general marker for venoms from snakes in the genus Agkistrodon found in North
      America.

PMID- 7505492
TI  - Time course of variations in rabbit cerebrospinal fluid levels of calcitonin gene
      related peptide- and substance P-like immunoreactivity in experimental
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Cerebral vasospasm after subarachnoid hemorrhage may
      result partially from the imbalance between vasodilator and vasoconstrictor
      factors. The vasodilator peptides substance P and calcitonin gene-related peptide
      contained in the trigeminovascular system are involved in the vasomotor
      phenomenon occurring after subarachnoid hemorrhage. The delayed arterial
      narrowing may reflect the time course of the release of these peptides.
      Therefore, we followed the time course of the changes in cerebrospinal fluid
      immunoreactivity of substance P and calcitonin gene-related peptide in a model of
      experimental subarachnoid hemorrhage. METHODS: Cerebrospinal fluid samples were
      taken in the basal state and at 30 minutes, 24 hours, and 3 days after a single
      injection of 1 mL autologous arterial blood into the cisterna magna of rabbits
      using a percutaneous suboccipital route. Substance P-like and calcitonin gene
      related peptide-like immunoreactivities were determined in centrifuged
      cerebrospinal fluid and plasma by use of enzyme immunoassay. RESULTS: Early (30
      minutes) after induced subarachnoid hemorrhage, there was a large increase in
      cerebrospinal fluid substance P-like immunoreactivity (P < .01) and calcitonin
      gene-related peptide-like immunoreactivity (P < .01). Arterial and hemorrhagic
      cerebrospinal fluid levels of substance P-like immunoreactivity were different (P
      < .03), indicating that the increased cerebrospinal fluid level did not result
      only from the blood contamination. Twenty-four hours after induced subarachnoid
      hemorrhage, the immunoreactivities of substance P and calcitonin gene-related
      peptide remained significantly higher than the basal level (P < .01). At day 3,
      both immunoreactivities had decreased to a level nonsignificantly different from
      the basal level. CONCLUSIONS: The early high values of the cerebrospinal fluid
      immunoreactivities for substance P and calcitonin gene-related peptide, apart
      from the contamination by arterial blood, probably resulted from the depletion of
      neurotransmitter peptides from the trigeminovascular fibers.

PMID- 7505493
TI  - The perfluorocarbon fluoromethyloadamantane offers cerebral protection in a model
      of isovolemic hemodilution in rabbits.
AB  - BACKGROUND AND PURPOSE: Perfluorocarbons (PFCs) are considered promising cerebral
      protection agents because they could combine the beneficial effects of decreased
      blood viscosity with enhanced oxygen-carrying capacity and oxygen tissue
      delivery, but trials of PFCs as hemodilutants have been very limited. We
      evaluated fluoromethyloadamantane (FMA), a new perfluorocarbon compound, as an
      isovolemic hemodilutant and compared it with low-molecular-weight dextran 40
      (D40) and a control group. METHODS: Through a transorbital craniectomy, the
      internal carotid, anterior, and middle cerebral arteries were coagulated to
      create a cerebral infarction in anesthetized, mechanically ventilated rabbits. No
      other experimental procedure was performed in control animals. In the two other
      groups, hemodilution was commenced 30 minutes after the arterial occlusion with
      either D40 or FMA. Hemodynamic parameters and brain and systemic temperature were
      monitored throughout the experiments. All animals were killed 6 hours after the
      arterial occlusion. RESULTS: Hemodynamic and metabolic parameters and blood
      oxygen content were not affected by the infusion of either FMA or D40. Brain and
      systemic temperature remained constant. The ratio of infarct volume to the
      hemispheric volume was 19.6 +/- 3.7% in the FMA group (n = 17), 19.9 +/- 4.6% in
      the D40 group (n = 16), and 40.3 +/- 5.7% in the control group (n = 17). The
      difference in infarct volume of both FMA and D40 animals compared with controls
      was statistically significant (P < .01) when tested with Student's t test. There
      was no significant difference between FMA and D40 groups. CONCLUSIONS: These
      results suggest that FMA has cerebral protective properties and should be
      purified, optimized, and further tested experimentally to develop a stable,
      efficient, and safe oxygen carrier, potentially suitable for clinical trials.

PMID- 7505494
TI  - P-selectin and intercellular adhesion molecule-1 expression after focal brain
      ischemia and reperfusion.
AB  - BACKGROUND AND PURPOSE: Polymorphonuclear leukocytes have been implicated in the
      development of the "no-reflow" phenomenon after focal cerebral ischemia and
      reperfusion. To further understand the role of granulocytes in microvascular
      occlusions, the responses of the granulocyte-endothelial cell adhesion molecules
      P-selectin and intercellular adhesion molecule-1 during middle cerebral artery
      ischemia and reperfusion were examined in a primate model. METHODS: Twelve
      adolescent male baboons were used for 2-hour middle cerebral artery occlusion (n
      = 3) or for 3-hour occlusion with 1-hour (n = 3), 4-hour (n = 3), and 24-hour (n
      = 3) reperfusion, and three separate unoperated primates served as controls. A
      quantitative immunohistochemical study of the microvascular distribution of P
      selectin and intercellular adhesion molecule-1 was performed using 10-microns
      frozen sections from basal ganglia analyzed with computerized light microscopy
      video imaging. RESULTS: Significant (P < .05) persistent upregulation of P
      selectin (beginning during ischemia) and transient upregulation of intercellular
      adhesion molecule-1 (at 1 and 4 hours of reperfusion) were observed on
      endothelium of selected post-capillary microvessels of the ischemic
      lenticulostriate artery territory. Platelet accumulation also occurred in this
      territory and was responsible for a significant proportion of the nonendothelial
      P-selectin signal at 24 hours after reperfusion. CONCLUSIONS: Focal cerebral
      ischemia/reperfusion stimulates endothelial P-selectin and intercellular adhesion
      molecule-1 expression in brain microvessels in the ischemic zone, which may
      contribute to enhanced leukocyte adherence and persistent activation.

PMID- 7505495
TI  - Developmental levels and nutritional status of children with the Trichuris
      dysentery syndrome.

PMID- 7505496
TI  - Thiacetazone--avoid like poison or use with care?
AB  - Recent 5 reports of severe cutaneous hypersensitivity reactions in patients
      infected with human immunodeficiency virus (HIV) and with tuberculosis treated
      with thiacetazone have prompted the World Health Organization to advise against
      the use of thiacetazone in patients known, or suspected, to be infected with HIV.
      Because the poorest countries will have great difficulty in replacing
      thiacetazone, the history, metabolism and possible mechanisms underlying the
      toxicity of this inexpensive, but problematic, drug are reviewed. Guidelines for
      National Tuberculosis Control Programme policies in response to thiacetazone
      toxicity are discussed, taking into account the differing levels of resources
      available to developing countries.

PMID- 7505497
TI  - L-arginine in 5-day perfusion of canine kidneys.

PMID- 7505498
TI  - Randomized trial of Sandostatin prophylaxis for preservation injury after
      pancreas transplantation.

PMID- 7505499
TI  - Role of neutrophils in the development of preservation injury after small bowel
      preservation for transplantation in the rat.

PMID- 7505500
TI  - Warm renal ischemia and reperfusion injury in rats treated with cyclophosphamide
      and/or granulocyte colony-stimulating factor.

PMID- 7505501
TI  - Prevalence of anti-HCV positivity in hemodialysis and renal transplant patients
      at our center.

PMID- 7505502
TI  - Small bowel tonometry: a possible technique for detecting early small bowel
      allograft dysfunction.

PMID- 7505503
TI  - Hematolymphoid cell trafficking, microchimerism, and GVH reactions after liver,
      bone marrow, and heart transplantation.

PMID- 7505504
TI  - [The amplification and overexpression of the mdr genes in Chinese hamster CHLV-79
      RJK cells resistant to ethidium bromide correlate with the presence of karyotypic
      markers of the amplification].
AB  - Evidence is provided that selection of the Chinese hamster cells CHLV-79 RJK with
      ethidium bromide results in amplification and overexpression of mdr family genes,
      one of which is encoding a transmembrane P-glycoprotein reducing the
      intracellular drug concentration. It is likely that the amplified copies are
      located at or near the sites of resident mdr gene localization to look as an
      abnormal chromosomal banding pattern in chromosome 1q26. In the following
      selection steps to higher drug concentration, the cells are keeping the degree of
      amplification, but mdr gene expression increases by many times. The data suggest
      that the resistance of the Chinese hamster cells CHLV-79 RJK to higher
      concentrations of ethidium bromide may be achieved via a variety of mechanisms,
      including as well mdr gene amplification as transcriptional regulation of these
      genes.

PMID- 7505505
TI  - [The isolation and characteristics of hetero-organic membrane antigens of kidney
      origin associated with Zajdela's hepatoma].
AB  - A hetero-organic antigen of kidney origin from cell membranes of the Zajdela
      ascitic hepatoma, and organospecific kidney antigens from cell membranes of
      kidney were purified using affinity chromatography with antibodies from
      organospecific antikidney serum immobilized with the CNBr-sepharose. By means of
      SDS-polyacrylamide gel electrophoresis it was shown that organospecific kidney
      antigens consisted of at least 6 components, but only one major band, with
      molecular weight near 50 kDa corresponds to a single component identified as a
      hetero-organic antigen of kidney origin purified from cell membranes of the
      Zajdela hepatoma.

PMID- 7505506
TI  - [A method for preparing a monolayer of frog brain cells for the cytophotometric
      determination of their DNA content].
AB  - An improved method for the squashing of the brain cells permitting a good
      preservation of cell nuclei and their subsequent quantitative cytophotometric
      evaluation is presented. By this method a monolayer of the brain cells can be
      easily obtained. The method was tested in cytophotometric study of the DNA
      content in the Feulgen stained cells of the frog hypothalamic preoptic area. The
      proposed method can be used for the quantitative evaluation of different
      histochemical reactions in the brain cells.

PMID- 7505507
TI  - Keratin-positive, epithelial membrane antigen-positive solitary pelvic tumor with
      ultrastructural features of large cell lymphoma.
AB  - A case of an unusual malignant solitary pelvic tumor is presented. The neoplastic
      cells were positive for keratin and epithelial membrane antigen. Although
      ultrastructural features (prominent nuclear pleomorphism, abundant polyribosomes,
      and absence of cell junctions) were those typically seen in large cell lymphomas,
      lymphoid markers were not detected, and immunoglobulin heavy-chain gene and T
      cell receptor beta-chain gene rearrangements were not identified. Combination
      chemotherapy resulted in complete remission.

PMID- 7505508
TI  - The immunocytochemistry of cytokeratin in fish tissues.
AB  - An increasing interest in fish species as sentinels of environmental pollution
      and in carcinogenesis research has led to the identification of diagnostically
      challenging neoplasms of uncertain cellular origin and the need for additional
      diagnostic methods. To determine the potential of using commercially available
      antibodies to intermediate filament proteins on paraffin-embedded fish tissues
      for immunocytochemistry in tumor diagnosis, the application of three antikeratin
      antibodies to normal adult tissues from two fish species was assessed. Multiple
      tissues from 12-14-in. striped bass (Morone saxatilis) and 6-month-old medaka
      (Oryzias latipes) of both sexes were fixed in Bouin's or formalin fixatives.
      Formalin-fixed neoplasms from several mammalian species, including cat, dog,
      hedgehog (Atelerix albiventris, Erinaceus europaeus), rhesus macaque (Macaca
      mulatta), and sloth bear (Melursus ursinus), were also used as positive controls.
      Using a strepavidin horseradish peroxidase method on paraffin-embedded tissues,
      the broad spectrum antibodies AE1/AE3 (Boehringer Mannheim, Indianapolis, IN) and
      MAK-6 (Triton Biosciences, Alameda, CA), which recognize most of the 19 human
      cytokeratins, and CAM 5.2 (Becton Dickinson, Mountain View, CA), which recognizes
      cytokeratins present in human liver, were used as primary antibodies. Epithelia
      from skin, gills, cornea, bile ducts, renal tubules, gastrointestinal tract, and
      thymus were strongly positive with AE1/AE3 and MAK-6 in striped bass, but
      nonepithelial tissues such as bone and muscle were negative. Skin, gills, cornea,
      and portions of the gastrointestinal tract were strongly positive in medaka with
      the same antibodies, whereas bile duct, renal, and intestinal epithelia were less
      so. Tissue digestion improved the intensity of staining, and fixation with
      Bouin's fixative improved results somewhat compared with formalin
      fixation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505509
TI  - Immunohistochemistry with keratin, vimentin, desmin, and alpha-smooth muscle
      actin monoclonal antibodies in canine mammary gland: normal mammary tissue.
AB  - Normal canine mammary gland tissue was studied immunohistochemically with
      monoclonal antibodies (MoAbs) directed against various human keratin types,
      vimentin, desmin, and alpha-smooth muscle actin. Both ductal and alveolar luminal
      cells were immunoreactive with MoAbs recognizing respectively human keratins no.
      7, 8, 18 and 19. In addition, some ductal luminal cells were labelled with a
      keratin 4 and a keratin 10 MoAb. Basal/myoepithelial cells were immunoreactive
      only with MoAbs directed against keratin 14, keratins 14 and 17, and alpha-smooth
      muscle actin. The vimentin MoAb merely labelled solitary loose intraluminal cells
      representing macro-phages or sloughed epithelial cells. These findings correspond
      largely to observations made in human breast tissue.

PMID- 7505510
TI  - Immunohistochemistry with keratin, vimentin, desmin, and alpha-smooth muscle
      actin monoclonal antibodies in canine mammary gland: benign mammary tumours and
      duct ectasias.
AB  - Duct ectasias (n = 2) and different types of benign canine mammary tumours (n =
      19) were studied immunohistochemically with monoclonal antibodies (MoAbs)
      directed against various human keratin types (K), alpha-smooth muscle actin,
      vimentin, and desmin. In the duct ectasias and in most tumours the epithelial
      structures revealed an inner and outer cell layer. The inner cell layer was
      characterized by labelling with K 7, 8, 18, 19 and mostly also with K 4 and/or K
      10 MoAbs. The outer cell layer was almost invariably labelled by K 14, K 14 and
      17, and a-smooth muscle actin MoAbs. The labelling patterns of both duct ectasias
      and tumours corresponded largely to the patterns observed in normal mammary gland
      tissue, although a more distinct heterogeneity was seen. Tumours
      histomorphologically assumed to be of a myoepithelial origin did not show
      immunohistochemical features of myoepithelial cells. The myoepithelial nature of
      the vast majority of spindle-shaped cells present in the adenomas of the complex
      type and in the fibroadenomas of the benign mixed type could not be confirmed
      immunohistochemically. These cells, however, unequivocally expressed vimentin,
      suggesting proliferation of stromal cells in these tumours, which in the
      fibroadenomas of the benign mixed type may show metaplasia to bone or cartilage.
      In the duct ectasias and in some tumours, a fraction of elongated stromal cells,
      probably representing myofibroblasts, was labelled with the alpha-smooth muscle
      actin MoAb.

PMID- 7505511
TI  - Immunohistochemistry with keratin, vimentin, desmin, and alpha-smooth muscle
      actin monoclonal antibodies in canine mammary gland: malignant mammary tumours.
AB  - Ten malignant canine mammary gland tumours and five metastases from three of
      these tumours were studied immunohistochemically with monoclonal antibodies
      (MoAbs) directed against different human keratin types (K), alpha-smooth muscle
      actin, vimentin, and desmin. In all tumours the neoplastic epithelium was rather
      homogeneously labelled with the keratin MoAbs RCK 102 (K 5 and 8) and CAM 5.2 (K
      8). The adenocarcinomas (n = 5), the solid carcinomas (n = 2), and the
      carcinosarcoma (n = 1) showed heterogeneous labelling with the MoAbs specific for
      luminal cell antigens in the normal canine mammary gland, i.e., K 18, K 7 and K
      19 MoAbs. These cells were also immunoreactive with K 4 and K 10 MoAbs. The
      spindle cell carcinomas (n = 2), however, did not react with these MoAbs. All
      tumours except one adenocarcinoma were characterized by the absence of
      immunoreactive labelling with the alpha-smooth muscle actin MoAb. In the solid
      carcinomas this was associated with the absence of labelling with one or both
      basal cell specific keratin MoAbs, i.e., 8.7 (K 14 and 17) and RCK 107 (K 14),
      respectively. In contrast, the other malignant tumours showed marked labelling of
      neoplastic epithelium with these MoAbs. Another remarkable finding was the
      labelling of a limited to moderate number of neoplastic epithelial cells with the
      vimentin MoAb. The presence of such labelling patterns in canine mammary gland
      tumours may be indicative of malignancy. Metastatic tumour tissues had a
      labelling pattern largely similar to that of the primary tumour, although also
      loss of reactivity for some keratin MoAbs was seen.

PMID- 7505512
TI  - Epitope analysis of tick-borne encephalitis (TBE) complex viruses using
      monoclonal antibodies to envelope glycoprotein of TBE virus (persulcatus
      subtype).
AB  - The arrangement of envelope protein epitopes of tick-borne encephalitis viruses
      (TBEV) (persulcatus or eastern subtype, Sofjin strain and ricinus or western
      subtype, Minsk-256 strain) and Kyasanur Forest disease virus (KFDV) was
      investigated using competitive binding of monoclonal antibodies against the
      Sofjin E protein. The E protein of TBEV Sofjin strain forms three antigenic
      domains: E1, E2 and E3, represented by 12, 9 and 2 epitopes respectively; two
      additional epitopes stand alone. Domains E1 and E2 are heterogeneous. On the
      epitope map of the Minsk-256 strain domain E3 remains intact, domains E1 and E2
      overlap and the relative arrangement of virus-neutralizing epitopes from E1 and
      E2 domains is changed. The epitope map of KFDV is significantly dissimilar to
      TBEV. The viruses can be distinguished by epitopes with identical serological
      reactivity. A satisfactory agreement between our epitope maps and previously
      published antigenic models of flavivirus envelope protein (Guirakhoo et al.,
      1989; Mandl et al., 1989a) was observed. The main difference of our map is that
      domains corresponding to domains B and C (Sofjin strain) and A, B and C (Minsk
      256 strain) in Heinz's model are overlapping. The results of competition analysis
      depend on the nature of the antigen (virion or purified protein) and the
      immunoassay technique.

PMID- 7505513
TI  - Antigenic analysis of feline calicivirus capsid precursor protein and its deleted
      polypeptides produced in a mammalian cDNA expression system.
AB  - An entire open reading frame in a cDNA encoding the capsid protein gene of feline
      calicivirus (FCV) was subcloned into a mammalian expression vector. After
      transfection of the constructed plasmid (pMCV-II) into COS-7 cells, the expressed
      protein was detected by indirect immunofluorescence assay (IFA) using a panel of
      monoclonal antibodies (MAbs) to the capsid protein of FCV. All of the MAbs
      reacted with the transfected COS-7 cells in IFA. The 76 kDa capsid precursor
      protein was demonstrated in an immunoblot analysis, indicating that the
      translated precursor protein was not processed into the matured capsid protein in
      this expression system. Two in-frame deleted and a frameshift mutated cDNAs were
      generated by using restriction sites within the capsid protein coding sequence in
      pMCV-II to analyze the antigenic sites of the protein. The results of IFA using
      the MAbs and COS-7 cells transfected with the deleted or mutated cDNAs suggested
      that three neutralizing epitopes had a conformational nature and that the other
      four linear epitopes were related to 74 amino acid residues between positions 381
      and 454 in the protein, in which high variation was known to be present among
      three strains of FCV.

PMID- 7505514
TI  - The hepatitis C virus genome: a guide to its conserved sequences and candidate
      epitopes.
AB  - A comprehensive analysis of reported hepatitis C virus genomic sequences
      comprising 151 partial or complete nucleotide sequences and 159 partial or
      complete amino acid sequences revealed an irregular composition of conserved and
      variable regions. There were but eight conserved nucleotide sequences, none
      outside the 5' noncoding and structural regions. A search among conserved amino
      acid sequences revealed 14 candidate B-cell epitopes, which were chosen mainly on
      the basis of their hydrophilicity profiles. Twenty five candidate T-cell epitopes
      were selected according to the criteria of absolute conservation of amino acid
      sequence, together with characteristic sequence motifs, amphipathic helical
      structure, or both. Conserved peptide sequences, with the characteristics of both
      B- and T-cell epitopes, were identified in the nonstructural 5 (NS5) region of
      the genome.

PMID- 7505515
TI  - [Enterochromaffin-like cells and their receptors: physiological role and
      physiopathological significance].
AB  - The enterochromaffin-like (ECL) cells represent the predominating endocrine cell
      population in the oxyntic mucosa of the stomach. They are under the influence of
      gastrin. Recently, a histamine production was shown within the secretory granules
      of ECL cells. ECL cells appear to play a crucial role in the physiology of
      gastric acid secretion. There are many unknowns concerning the intervention of
      other trophic factors in addition to gastrin and concerning the receptors located
      on the cells. ECL cell hyperplasia is a well documented consequence of
      hypergastrinemia. The latter can result from a gastrinoma or from a reduction of
      gastric acid secretion related to pernicious anemia or to long-term treatment
      with antisecretory drugs.

PMID- 7505516
TI  - [The prerequisites for learning reading and writing. Cognitive screening in the
      nursery schools of the area of Vicenza ULSS 8 in the years 1983-1990
      (N.>18,000)].
AB  - The author, after a short introduction concerning the importance of reading and
      writing in modern society, analyses the prerequisites necessary for their
      learning. Cognitive screening was carried out for 8 years (1983-1990) on the play
      school population of ULSS n. 8 in Vicenza, and the method used in over 18,000
      cases is reported. The investigation protocol, expressly calibrated for this
      particular population, and the results obtained, are described. A long term
      follow-up was performed in order to verify the correspondence between the degree
      of impairment observed during screening and the positive performance at primary
      school level of the same subjects. Some final considerations are made concerning
      the effectiveness of different communication tests in predicting problems related
      to the learning of reading and writing.

PMID- 7505517
TI  - Hydrogen peroxide stimulates endocytosis in cultured bovine aortic endothelial
      cells.
AB  - Fluid-phase uptake of macromolecules by cultured bovine aortic endothelial cells
      was measured using FITC-dextran (70,000 Da). Low doses of hydrogen peroxide added
      extracellularly stimulated the uptake of macromolecules by the endothelial cells.
      There was no general increase in the passive permeation or the transport across
      the cell layer. Moreover, when endothelial cells were stimulated with phorbol
      myristate acetate (PMA), macromolecules uptake was also enhanced. The PMA effect
      was blocked with superoxide dismutase (SOD) and catalase, suggesting a pivotal
      role of oxygen metabolites in fluid phase uptake of macromolecules by endothelial
      cells.

PMID- 7505518
TI  - Tissue-specific reduction of galanin content in the pancreas in alloxan diabetes
      in the mouse.
AB  - Galanin inhibits insulin secretion and has been proposed to function as a
      sympathetic neurotransmitter in the endocrine pancreas in some species, for
      example in the dog. In this study, pancreatic and adrenal gland galanin content
      were measured following experimental diabetes induced by alloxan in mice. Three
      days after administration of alloxan (70 mg kg-1, i.p.) in normal mice,
      pancreatic content of galanin-like immunoreactivity (GLIR) was reduced to 65 +/-
      11% of that in untreated controls (P < 0.01), whereas adrenal gland GLIR was
      unchanged. Similarly, 8 days after alloxan administration, pancreatic GLIR was
      reduced (P < 0.002), whereas adrenal gland GLIR was unaffected. Pancreatic GLIR
      also inversely correlated with plasma glucose levels (r = -0.5055, P < 0.005). To
      distinguish between the direct effects of alloxan vs. indirect metabolic effects
      induced by the drug, alloxan-diabetic mice were treated with insulin twice daily,
      which normalized the plasma glucose levels (7.6 +/- 0.3 mmol l-1). Pancreatic
      GLIR was then not significantly different from controls. Thus pancreatic but not
      adrenal gland GLIR content is reduced in alloxan-induced diabetes in mice. The
      data support a role for galanin as a pancreatic sympathetic neurotransmitter
      which may participate in the metabolic alterations seen in alloxan diabetes in
      mice.

PMID- 7505519
TI  - [Clinical evaluation of a new kit (IMX PA Dainapack) for detection of serum
      prostate specific antigen].
AB  - A study of the clinical utility of the IMx PA Dainapack, a new kit for detection
      of serum prostate specific antigen (PSA) by a fully automated enzyme immunoassay
      (EIA) system, was conducted. Results concerning reproducibility, dilution
      linearity and sensitivity were good. The excellent assay performance of this kit,
      particularly in terms of its high sensitivity (0.1 ng/ml), was confirmed. The
      upper limit of normal was determined to be 4.0 ng/ml from the mean +/- 3 S.D.
      (3.79 ng/ml) in healthy male controls (n = 244). Using 4.0 ng/ml as the upper
      limit of normal, 6 of 244 healthy male controls (2%) were positive. In various
      urinary diseases, 173 of 192 prostatic cancer (90%) and 46 of 112 benign
      prostatic hypertrophy (BPH) (41%) cases were positive. In prostatic cancer, the
      positive rates increased with the advance in clinical stage and in stage A the
      positive rate was especially high (8 of 12 (67%) were positive). On the other
      hand, using the BPH group as a negative control, the maximum accuracy rate for
      prostatic cancer had a cut-off value of 8.0 ng/ml. Thus, 8.0 ng/ml is an
      appropriate cut-off value differentiating prostatic cancer from BPH while 4.0
      ng/ml is the cut-off value between the normal group and those with prostatic
      cancer (including stage A) and BPH. In the follow-up patients with prostatic
      cancer, serum PSA values measured by this kit reflected the effectiveness of
      treatment. The correlations between values obtained with the IMx PA Dainapack and
      6 current kits were good (r = 0.93 to 0.99) but the values differed with the
      kit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505520
TI  - [Transurethral microwave thermotherapy for benign prostatic hyperplasia: clinical
      evaluation with International Prostate Symptom Score (I-PSS)].
AB  - Forty patients with symptomatic benign prostatic hyperplasia were treated with a
      single session of transurethral microwave thermotherapy (TUMT) using a
      Prostatron. The clinical effectiveness was evaluated by analyzing the subjective
      and objective responses following the treatment. The International Prostate
      Symptom Score (I-PSS) and quality of life (QOL) scale were used to evaluate the
      subjective symptoms. At three months after treatment, significant improvements in
      I-PSS (p < 0.0001). QOL (P < 0.0001), and peak flow rate (Qmax) (p < 0.05) were
      observed. Improvement of both I-PSS and Qmax was found in 90% (18/20) of the
      patients at 2 months. Although 15 patients noted transient urinary retention and
      15 patients had mild to moderate macroscopic hematuria immediately after TUMT, no
      severe adverse effects occurred during the follow-up period. A significant
      correlation was found between I-PSS improvement and the total thermal dose
      delivered. However, the thermal dose could not be predicted in each case. The
      preliminary findings suggest that TUMT by Prostatron is safe and effective as a
      nonsurgical treatment for benign prostatic hyperplasia. The clinical response
      seems to be thermal dose dependent. I-PSS is clinically sensitive and is useful
      in practice.

PMID- 7505521
TI  - [Long-term results and indications of intraurethral stents in elderly patients
      with prostatic hypertrophy complaining of urinary retention].
AB  - Thirty-two elderly male patients with benign prostatic hypertrophy complaining of
      urinary retention were treated by polyurethane intraurethral stents. All of them
      were unfit for prostatic surgery due to the presence of several complications,
      and had been indwelt with a urethral balloon catheter. Cystometry before stent
      insertion was performed in 23 of the 32 patients. Eleven patients showed
      overactive bladder, 5 patients normal bladder, and 7 patients underactive
      bladder. Duration of stent indwelling ranged from 2 days to 22 months (mean 6.7
      months), and stent could successfully function for more than 6 months in 20 of
      the 32 patients (62.5%). Nine of these 20 patients (45%) could keep continence of
      urine, and urinary tract infections improved in 7 of these 20 patients (35%). The
      stent failed in 4 of the 5 patients who had had previous operations for prostatic
      hypertrophy. In a comparison of the findings of urodynamic study prior to
      insertion of stent with the results of the stent, the results were significantly
      better in the patients with overactive or normal bladder than in those with
      underactive bladder (p < 0.05, chi-square test). Bladder stone formation was
      found in one patient and was the only complication among the 32 patients. In
      conclusion, stent placement without incontinence or urinary tract infection can
      be successful for more than 6 months in patients who do not have an underactive
      bladder and who had not had a previous prostatic operation.

PMID- 7505522
TI  - [A clinical study of 17 cases of penile cancer].
AB  - A clinical evaluation of 17 patients with penile cancer treated in our hospital
      from 1965 to 1991 were surveyed. They were between 34 and 74 years old with a
      mean age of 63.8 years. The average interval between the onset and the first
      visit was 22.8 months. Fourteen patients (83%) complained of the manifestation of
      a tumor and 14 patients (83%) were phimotic. The stage classified according to
      Jackson was Stage I for 6, Stage II for 6, Stage III for 4 and Stage IV for 1
      patient. At the first visit, the inguinal lymph nodes were palpated in 8 patients
      and metastasis was confirmed in 5 (63%) of them. Surgical treatment was given to
      15 patients (88%) (radical or partial penectomy was performed in most cases).
      Chemotherapy was given to 9 patients (60%) (main chemotherapeutic agent was
      bleomycin) and irradiation to 5 patients (30%). The overall 3-year survival rate
      was 71%, and 5-year survival rate was 56%. The 5-year survival rate in the low
      stage group (Stage I, II) was 75%, while that in the high stage group (Stage III,
      IV) was 0%, showing a significant difference.

PMID- 7505523
TI  - [Prophylactic combination therapy after TUR of superficial bladder cancer].
AB  - We evaluated 63 patients with superficial bladder cancer (pTa, pTl) who were
      treated with instillation of bleomycin +/- bacillus Calmette-Guerin (BCG) and
      administration of uraciltfutraful (UFT) for prophylaxis of tumor recurrence after
      transurethral resection (TUR). The patients were randomly assigned to groups A
      and B after transurethral resection by the closed envelope method. Group A (34
      cases) was designed as continuous diluted intravesical instillation of bleomycin
      (120 mg/2,000 ml saline solution/day repeated for 3 days), instillation BCG (40
      mg/40 ml saline solution/weekly 6 times) and UFT (400 mg orally/day for 2 years
      maximum). Group B (29 cases) was designed as the aforementioned minus BCG
      instillation. Cumulative non-recurrence rates in group A and group B were 80.1%
      and 72.1% at the time of three years, which revealed no significant difference
      between the two groups (p = 0.265, generalized Wilcoxon test). The high recurrent
      incidence of superficial bladder cancer is primarily due to the multifocal nature
      of the cancer or implantation of tumor cells at the time of the subsequent
      transurethral resection. The procedure was performed safely with no severe side
      effects. Our method might be useful to reduce the recurrences of superficial
      bladder cancer after transurethral resection of bladder (TUR).

PMID- 7505524
TI  - [Transurethral microwave thermotherapy for benign prostatic hyperplasia].
AB  - Transurethral microwave thermotherapy (TUMT) of prostate was administered to 10
      patients with bladder outlet obstruction due to benign prostatic hyperplasia. The
      mean age of the patients was 74.4 years (range 63 to 85). The Prostatron device,
      which provides microwave heating of the prostate and conductive cooling of the
      urethra was used, and the prostate was heated with a calculated intraprostatic
      temperature of 45.5 degrees C for 55 minutes. No anesthesia was required for most
      of the patients. The clinical effects were evaluated at 4-6 weeks and 3 months
      after treatment. The symptomatic scores improved in the majority of patients.
      There was no significant change in prostate volume. The maximum flow rate and
      average flow rate were increased at 6 weeks and 3 months, but there was no
      significant change. The only side effects were transient hematuria and short-term
      obstruction secondary to urethral edema. In comparing TUMT with the transurethral
      resection of prostate (TUR-P), the maximum flow rate after TUMT was lower than
      that after TUR-P and the improvement of residual urine after TUMT was lower than
      that after TUR-P.

PMID- 7505525
TI  - [New microwave transurethral hyperthermia for benign prostatic hyperplasia-
      clinical evaluation].
AB  - Several types of hyperthermic apparatuses are employed to treat benign prostatic
      hyperplasia (BPH). As the prostate surrounds the urethra, we believed that
      transurethral heating allowed for more efficient and uniform heating. A new
      effective apparatus for this objective was developed. The size of our
      hyperthermic apparatus was about 52 x 45 x 20 centimeters and the originating
      frequency was 2,450 +/- 30 MHz. We used T-type thermocouples as temperature
      sensors. The transurethral applicator had a cooling system. Thirty patients
      complaining of obstructive symptoms due to BPH were treated. Hyperthermia was
      performed 3-6 times for each patients (two times per week). Each procedure was
      performed for 60 minutes. The temperature was controlled at 39 degrees C on the
      urethral surface (43 degrees C at prostate). The overall efficacy of this
      treatment was effective in 23 of the 30 patients (76.7%). In addition, there were
      no severe complications. As the size of this apparatus was miniaturized, it could
      be used at the bed side.

PMID- 7505526
TI  - RNA synthesis in porcine blastomere nuclei introduced into in vitro matured
      ooplasm.
AB  - The objective was to investigate the RNA synthesis in porcine blastomere nuclei
      upon transplantation into in vitro matured enucleated oocytes. Nuclei from 2- to
      8-cell porcine embryos were introduced into the ooplasm of in vitro matured and
      enucleated porcine oocytes by electrofusion, and the resultant reconstructed
      embryos were cultured in vitro. Before fusion or at different intervals after
      this event embryos were incubated with [3H]-uridine, fixed, and histologically
      processed for autoradiography in order to detect RNA synthesis. About two thirds
      of the embryos were considered to depict normal development. All blastomeres
      displayed pronounced RNA synthesis before fusion, at 3 and 9 h after fusion the
      synthesis decreased or ceased, and at 24-49 h some embryos resumed synthesis at
      the 1- to 2-cell stage.

PMID- 7505527
TI  - Senegal haplotype is associated with higher HbF than Benin and Cameroon
      haplotypes in African children with sickle cell anemia.

PMID- 7505528
TI  - Cryoglobulinemic membranoproliferative glomerulonephritis associated with
      hepatitis C virus.
AB  - A striking association between hepatitis C virus (HCV) and mixed cryoglobulinemia
      (MC) has been reported by various authors, regardless of the presence of chronic
      hepatitis. The aim of this study is to evaluate the prevalence of HCV-related
      markers in cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) which
      is one of the most severe complications of MC. Antibodies against HCV have been
      detected by second-generation Chiron ELISA and RIBA in 26/26 (100%)
      cryoglobulinemic MPGN. In addition, serum HCV RNA, expression of the ongoing
      viral replication, was present in 7/7 patients by the polymerase chain reaction
      technique. The high percentage of anti-HCV seropositivity suggests that this
      virus may play an important role in the pathogenesis of this immunemediated
      glomerulonephritis.

PMID- 7505529
TI  - Peritoneal fluid concentrations of the cytokine RANTES correlate with the
      severity of endometriosis.
AB  - OBJECTIVE: Endometriosis is a common gynecologic disorder in which the
      concentration and activation of peritoneal macrophages are increased. The goal of
      this study was to quantify pelvic fluid concentrations of two cytokines involved
      in macrophage recruitment and activation. STUDY DESIGN: A case-control study of
      women undergoing pelvic surgery was conducted by collecting peritoneal fluid from
      12 women without evidence of endometriosis (controls), 12 with mild, and 12 with
      moderate to severe endometriosis. Concentrations of RANTES and interferon gamma,
      soluble cytokines known to recruit and activate macrophages, were quantified by
      enzyme-linked immunosorbent assays. RESULTS: Pelvic fluid concentrations of
      RANTES are elevated in women with endometriosis and the levels correlate with the
      severity of disease. By contrast, concentrations of interferon gamma appear
      unaffected by the presence of or severity of endometriosis. CONCLUSION: The
      findings indicate that RANTES, a cytokine with potent chemotactic activity for
      human monocytes, may play an important role in the recruitment of peritoneal
      macrophages in endometriosis.

PMID- 7505530
TI  - Maternal serum screening for fetal Down syndrome in the United States: a 1992
      survey.
AB  - OBJECTIVE: Our purpose was to determine the status of screening for fetal Down
      syndrome in the United States in 1992. STUDY DESIGN: Information was sought from
      laboratories participating in two proficiency testing programs. RESULTS: The 301
      responding laboratories (98%) annually provided services to 2,113,000 pregnant
      women. Of these laboratories, 242 provided Down syndrome screening (1,924,000
      pregnant women); 55% used alpha-fetoprotein levels alone, 30% used alpha
      fetoprotein, unconjugated estriol, and human chorionic gonadotropin combined, and
      14% used alpha-fetoprotein and human chorionic gonadotropin combined. All
      laboratories used clinically validated analytes. Nearly all screened at
      appropriate gestational ages, used a validated algorithm, and used risk as the
      screening variable. However, many laboratories, especially smaller ones, were
      unable to monitor their performances adequately. CONCLUSION: Since 1988 maternal
      serum screening for Down syndrome has approximately doubled, and other analyte
      measurements have been added in nearly one fourth of the screened pregnancies.
      Most laboratories appear to be performing adequately, although there is room for
      improvement.

PMID- 7505531
TI  - Keratin expression reveals mosaic differentiation in vaginal epithelium.
AB  - OBJECTIVE: Analyzing the expression of keratins has proved to be valuable for
      identifying of pathways of epithelial differentiation. In stratified epithelia
      K10 and K13 are representative for either the keratinizing (epidermal-type) or
      the nonkeratinizing pathway. STUDY DESIGN: We have investigated keratin
      expression in "normal" vaginal epithelium from 30 women, applying two-color
      immunofluorescence with monoclonal antibodies to K10 and K13 on cryostat sections
      and cell smears. RESULTS: A differential expression pattern of vaginal cells
      dependent on their localization within the epithelium was found. In cells of the
      first suprabasal layers differentiation began and became identifiable by a weak
      expression of K13. The adjacent layers displayed cells that concurrently
      expressed K10 and K13. In contrast, cells within the superficial strata expressed
      exclusively either one of the two keratins. CONCLUSION: Thus vaginal epithelium
      appears to be mosaic in differentiation, showing simultaneous expression of
      keratins K10 and K13, thought to be representative for distinct routes of
      differentiation.

PMID- 7505532
TI  - Inhibition of nitric oxide synthase does not affect alpha 2-adrenergic-mediated
      cerebral vasoconstriction.
AB  - We assessed whether blocking nitric oxide (NO) synthase alters the cerebral blood
      flow (CBF) response to alpha 2-adrenergic stimulation during isoflurane
      anesthesia in dogs. In control animals (n = 6), CBF (microspheres), cerebral
      oxygen consumption (CMRO2), and electroencephalograph (EEG) were measured after 1
      h of isoflurane (1.4% end-tidal) and before and 5, 10, and 20 min after injection
      of an alpha 2-adrenergic receptor agonist (dexmedetomidine 10 micrograms/kg,
      intravenous bolus). Dogs in a second group (n = 6) were treated similar to
      control animals except that an irreversible blocker of NO synthase, N omega-nitro
      L-arginine methyl ester (L-NAME; 40 mg/kg) was administered 1 h before induction
      of anesthesia. In control dogs, dexmedetomidine decreased CBF by 37% (P < 0.05).
      Blood flow remained decreased for the 20 min observation period in all brain
      regions except cerebellum and caudate. In the L-NAME group, control CBF was 45%
      less than baseline flow in the control group (P < 0.05) and dexmedetomidine
      further decreased CBF from 41 +/- 7 mL x 100 g-1 x min-1 to 24 +/- 2 mL.100 g-1 x
      min-1 (P < 0.05). There was no difference between groups in the percent of
      reduction of blood flow in any region after dexmedetomidine administration.
      Control CMRO2 was similar in the two groups and was unchanged by dexmedetomidine.
      These data demonstrate that L-NAME reduces CBF and that block of NO synthase does
      not affect alpha 2-adrenergic-mediated decreases in CBF during isoflurane
      anesthesia.

PMID- 7505533
TI  - Regulation of acute phase gene expression following surgery and endotoxin
      administration in the anesthetized pig.
AB  - BACKGROUND: The hepatic acute phase response (APR) reflects an organism's
      integrated response to stress. This APR results in augmented synthesis and
      secretion of specific procoagulants and antiproteases and a complementary
      decrease in the synthesis and secretion of several constitutive proteins, such as
      albumin. The cytokines tumor necrosis factor (TNF) or interleukin-6 (IL-6) have
      been identified as proximal mediators of the APR in response to endotoxin stress.
      The authors hypothesized that TNF, IL-6, or both would be the proximal mediators
      of the APR in response to anesthesia and surgical stress. METHODS: The effects of
      a standardized surgical stress on the APR in pigs under general anesthesia with
      sodium pentobarbital and ketamine hydrochloride was investigated. Acute phase
      gene transcription was assayed in nuclei from serial liver biopsies obtained
      before and after 2.5 h of surgical stress, and after endotoxin administration.
      Tumor necrosis factor and IL-6 mRNA levels in this liver tissue were examined by
      Northern blot hybridization, and simultaneous plasma levels of these cytokines
      were measured using bioassays. RESULTS: The transcription rates of three positive
      acute phase genes--chymotrypsin inhibitor, inter-alpha-trypsin inhibitor and beta
      fibrinogen--increased seven-, six-, and twofold, respectively (P < 0.05), and the
      transcription rate of albumin, a negative acute phase gene, decreased to 34% of
      baseline (P < 0.01) during the 2.5 h of anesthesia and surgical stress. During
      this initial 2.5 h, plasma concentrations of TNF and IL-6 did not change. Hepatic
      IL-6 mRNA expression was never observed, and TNF mRNA expression was undetectable
      in six of seven pigs. Subsequent 10-micrograms/kg endotoxin administration caused
      20- and 100-fold increases in plasma concentrations of TNF and IL-6, respectively
      (P < 0.01), and were associated with substantial hepatic expression of the TNF
      and IL-6 mRNAs. These increments in cytokines were not associated with any
      further increase in the acute phase gene transcription rates. Thus, the APR was
      initially regulated at the transcriptional level during surgical stress
      independent of, and not augmentable by, an endotoxin-provoked increase in either
      plasma levels or hepatic mRNA expression of TNF or IL-6. CONCLUSIONS: Surgical
      stress induced hepatic acute phase gene transcription within 2.5 h in the absence
      of either systemic or local (hepatic) increases in TNF or IL-6. Subsequent
      endotoxin-induced increases in TNF or IL-6 did not alter this surgical stress
      induced acute phase gene transcription.

PMID- 7505534
TI  - Endothelium, anesthetics, and vascular control.

PMID- 7505535
TI  - Ion channels in vascular smooth muscle. Physiology and pharmacology.

PMID- 7505536
TI  - Pathogenesis and pharmacologic modulation of the cutaneous late-phase reaction.
AB  - Late-phase reactions that occur in response to local antigen challenge have been
      demonstrated in the skin, nose, and lungs of humans. Late-phase reactions in
      these organs involve many mechanisms important in diseases such as atopic
      dermatitis, allergic rhinitis, and asthma. For this discussion, late-phase
      reaction research involving the skin model will be presented. Past research
      focused on the inflammatory components of late-phase reactions, but results were
      confounded by abrasion-related nonspecific inflammatory changes. Newer, less
      traumatic skin test methods have clarified the involvement of humoral and
      cellular elements in cutaneous late-phase reactions and demonstrated the efficacy
      of agents commonly used to treat allergenic conditions. Antigen challenge
      triggers the local release of histamine, prostaglandin D2, leukotriene C4, and
      tryptase. Dermal infiltrate abounds with eosinophils, basophils, neutrophils, and
      mononuclear cells several hours after challenge. Several investigators have shown
      that soluble proinflammatory cytokines are produced by cells at the antigen
      challenged site. Several of these cytokines may activate eosinophils and
      basophils, which release mediators of inflammation. Some of the newer nonsedating
      antihistamines appear to possess anti-inflammatory properties that may be
      unrelated to histamine antagonism and that might alter late inflammatory events
      of allergic disease.

PMID- 7505537
TI  - Image analysis of myelination in second-trimester human fetal spinal cords at
      risk for HIV-1 infection.

PMID- 7505538
TI  - HIV-1 reverse transcriptase. A diversity generator and quasispecies regulator.

PMID- 7505539
TI  - Preliminary report on ultrasound guided transrectal prostatic biopsy.
AB  - Transrectal ultrasound (TRUS)-guided transrectal biopsy was performed on 15
      patients. Histological findings were carcinoma in three cases (20%), prostatitis
      in three cases (20%) and glandular atypia in two cases (13%). All lesions were
      located in the peripheral zone. Hyperechoic lesions on TRUS were seen in two of
      the three cases of prostatic carcinoma while hypoechoic lesions were seen in all
      three cases of prostatitis. Directed biopsies established the diagnosis in six
      cases. However, random biopsies revealed that the extent of involvement was
      underestimated in five of these six cases. In addition, random biopsies
      established the diagnosis in two cases where the directed specimen was negative.
      Where both digital rectal examination (DRE) and TRUS were positive for nodules
      and the prostatic specific antigen (PSA) was elevated, the histology was positive
      in 100%. Where both the DRE and TRUS were negative, the histology was negative
      irrespective of the PSA level. Patient acceptance of the procedure was high.
      Complications to the procedure were haematuria, passing blood per rectum and
      fever.

PMID- 7505540
TI  - Percutaneous biliary drainage into the jejunum via a tube gastrostomy in patients
      with complete biliary obstruction: a report of two cases.
AB  - In recent years, percutaneous gastrostomy has been used to return bile draining
      from percutaneous transhepatic drainage catheters in patients with complete
      biliary obstruction that could not be bypassed surgically or stented either
      percutaneously or endoscopically. We report our initial experience with two
      patients in whom the combined percutaneous and endoscopic technique was used to
      divert the bile back into the jejunum.

PMID- 7505541
TI  - Phosphotyrosyl-proteins in human breast cancer.
AB  - The content of phosphotyrosyl-proteins, substrates of protein tyrosine kinases,
      was evaluated by immunohistochemical staining in human breast cancers, and its
      relation to the prognostic factors of cancers was studied. Both protein tyrosine
      kinase activity and the content of various growth factor receptors and
      oncoproteins with this activity have been shown to be elevated in breast cancers.
      The magnitude of the increase has been reported to have prognostic significance;
      greater increases were associated with poorer prognostic factors of cancers and
      with shorter survival of patients. Immunohistochemical staining demonstrated a
      low level of phosphotyrosyl-proteins in normal human breast tissue and in 44% of
      breast cancers. In 56% of breast cancers the level of phosphotyrosyl-proteins was
      increased; however, these cancers did not differ from cancers containing a low
      level with respect to prognostic factors such tumor size, histological
      differentiation grade or axillary lymph node metastases. The increased content of
      phosphotyrosyl-proteins in the majority of human breast cancers further supports
      the observations that growth factor receptors and oncoproteins with tyrosine
      kinase activities are activated in these cancers. The content of phosphotyrosyl
      proteins, however, has no relation to the prognostic factors of cancers.

PMID- 7505542
TI  - Loco-regional treatment for esophageal cancer with bleomycin adsorbed to
      activated carbon particles.
AB  - Bleomycin (BLM) was adsorbed to activated carbon particles (BLM-CH), and the
      effective distribution of BLM in the regional lymph nodes and surrounding
      connective tissues was studied in 10 patients with mid-thoracic esophageal
      cancer. One ml of BLM-CH was injected submucosally into the tumor and normal
      esophageal wall endoscopically one or three days prior to operation. BLM activity
      was found both in the lymph nodes and connective tissues, not only in the
      mediastinal region but in the cervical and abdominal regions. Degenerative or
      inflammatory changes were microscopically observed in 6 out of 23 lymph nodes
      with metastatic foci. BLM-CH could be a useful tool in targeting chemotherapy for
      esophageal cancer.

PMID- 7505543
TI  - Serum CYFRA 21-1 assay in squamous cell carcinoma of the cervix.
AB  - Squamous cell carcinoma antigen (SCC) is the best known marker for squamous cell
      carcinoma of the cervix as well as of the lung, oesophagus, head and neck and
      anal canal. Elevated levels of cytokeratin 19-fragments (CYFRA 21-1) have
      recently been detected in a large proportion of patients with non small cell
      cancer of the lung, and in particular of those with squamous cell carcinoma.
      Serum levels of CYFRA 21-1 (cut-off = 1.06 ng/mL) and SCC (cut-off = 2 ng/mL)
      were measured in blood samples collected before treatment from 15 patients with
      cervical intraepithelial neoplasia (CIN), 56 patients with cervical cancer, 48
      patients with endometrial cancer, and 361 patients with benign uterine diseases.
      Serum CYFRA 21-1 values in patients with CIN were superimposable on those
      detected in patients with benign uterine diseases. Conversely, serum CYFRA 21-1
      levels were higher in patients with cervical cancer (p < 0.05) and in patients
      with endometrial cancer (p < 0.05) than in those with benign uterine diseases.
      There was no significant difference in serum CYFRA 21-1 levels between cervical
      and endometrial cancer, and, as regards cervical cancer, there was no significant
      difference in antigen values between squamous cell carcinoma and adenocarcinoma.
      Among patients with squamous cell carcinoma of the cervix, CYFRA 21-1 values
      correlated with FIGO stage (stage IIb-IV vs stage Ib-IIa, p = 0.0303). Elevated
      CYFRA 21-1 levels were found in 20.0% of patients with CIN, in 41.7% of patients
      with squamous cell carcinoma of the cervix, in 62.5% of patients with
      adenocarcinoma of the cervix, in 45.8% of patients with endometrial cancer, and
      in 13% of patients with benign uterine diseases. Serum SCC was more sensitive
      than serum CYFRA 21-1 for both early and advanced squamous cell carcinoma of the
      cervix; these preliminary data seem to show that serum CYFRA 21-1 is of limited
      value for the management of patients with this malignancy.

PMID- 7505544
TI  - The role of lipid-associated sialic acid (LSA) and prostate specific antigen
      (PSA) in the follow-up of prostatic cancer.
AB  - According to the most recent US cancer statistics, prostatic cancer almost equals
      lung cancer as the most frequent cause of death from cancer in men. The search
      for diagnostic methods as well as control examinations have therefore gained
      great importance. The present study reveals that--in addition to rectal touch,
      sonography and biopsy of the prostate--the determination of both PSA as organ
      specific marker and lipid-associated sialic acid (LSA) as a general tumor marker,
      is well suited for follow-up and monitoring treatment. With regard to the follow
      up, the combined determination of PSA and LSA in serum of patients with prostatic
      cancer achieves a higher sensitivity as compared to PSA alone (increase of 30
      40%). LSA is a good indicator for the presence of metastases. Therefore, the
      determination of LSA should become an integral part of treatment monitoring and
      detection of metastatic disease in patients with prostatic cancer.

PMID- 7505545
TI  - A review of bacterial resistance to antimicrobial agents in tropical countries.

PMID- 7505546
TI  - Traditional practices and other socio-cultural factors affecting the health of
      children in Saudi Arabia.
AB  - The medical services in Saudi Arabia have improved tremendously over the last two
      decades, and health centres are easily accessible to more than 93% of the
      population. Nevertheless, folk medicine, including cautery, bone setting, manual
      tonsillectomy, uvulectomy, use of herbal medicines and use of harmful teething
      powders, in addition to religious healing, is widely practised. Reasons include
      influence of grandparents, religious beliefs and failure of modern medicine to
      find an answer to some chronic disorders. These problems, and measures to
      counteract them, are discussed. Attention is also drawn to some of the harmful
      'imported' practices that are affecting the health of children, including
      smoking, children driving cars and problems resulting from dependence on
      housemaids to bring up children. Some nutritional beliefs and taboos are also
      mentioned.

PMID- 7505547
TI  - Ophthalmia neonatorum in Bangkok: the significance of Chlamydia trachomatis.
AB  - In a prospective 2-month case-controlled study, 17 cases of neonatal
      conjunctivitis were diagnosed. A statistically significant association between
      neonatal conjunctivitis and the presence of Chlamydia trachomatis (five cases)
      and Staphylococcus aureus (five cases) was shown. No cases of gonococcal
      conjunctivitis were found, perhaps because of the routine use of silver nitrate
      (1%) drops. C. trachomatis conjunctivitis could not be diagnosed on clinical
      grounds, nor was examination of Giemsa-stained conjunctival scrapes sufficiently
      sensitive to detect all cases. In order to prevent the long-term morbidity of C.
      trachomatis infection in both mother and child, specific aetiological diagnosis
      using immunodiagnostic or cultural procedures is required.

PMID- 7505548
TI  - Age-specific prevalence of hepatitis B surface antigenaemia in hospitalized
      children at Port Moresby, Papua New Guinea (a cross-sectional study with
      implications for the Hepatitis B Control Programme).
AB  - A cross-sectional analysis of the prevalence of hepatitis B surface antigenaemia
      in cord blood from 50 newborn babies and in blood from 415 children admitted to
      the children's ward of Port Moresby General Hospital indicates that perinatal
      vertical transmission is likely to be important and that there is a high rate of
      horizontal transmission in the 1st few years of life. Thirteen per cent of
      infants aged 3-5 months and 29-30% of those over 2 years of age were strongly
      positive for hepatitis B surface antigen. Open sores and poor hygiene are likely
      to play a significant role in the high level of horizontal transmission of
      hepatitis B virus (HBV) in our context. Our findings give support and urgency to
      the current active immunization policy against HBV, beginning as soon as possible
      after birth.

PMID- 7505549
TI  - The problem of non-attendance at a paediatric tuberculosis outpatient clinic.
AB  - A total of 146 children receiving treatment for pulmonary tuberculosis at the
      University of Benin Teaching Hospital over a 5-year period were studied in order
      to determine the pattern of attendance, factors responsible for non-completion of
      treatment and the health status of non-attenders. There were 70 (48%) non
      attenders and the mean duration of treatment before default was 20 weeks (range:
      4-60). The factors mitigating against treatment completion included low maternal
      education level, disruptive family events and equating disappearance of the
      tuberculosis symptoms with cure of the disease. Of the non-attenders, 51 (72.9%)
      practised self-medication with the anti-tuberculosis drugs, often given
      intermittently and beyond the period otherwise allowable. Nineteen of the 70
      patients who defaulted still had major health problems at the time of home visit.
      Of these, five were later hospitalized while the others were given fresh
      appointments. We conclude that supervision of treatment at home will minimize non
      attendance but at the moment this service is not available at the study locale
      because of inadequate resources and the magnitude of the tuberculosis problem.

PMID- 7505550
TI  - Acute lower respiratory tract infection in hospitalized children in Zimbabwe.
AB  - A descriptive study was undertaken to document clinical and socio-demographic
      features and also to identify risk factors for mortality in children hospitalized
      with acute lower respiratory tract infection (ALRI). A total of 704 children aged
      from 1 month to 5 years admitted to Harare Central Hospital were studied. The
      peak age group was between 1 and 6 months. Seventy per cent of the children were
      found to have normal nutrition and 12% severe malnutrition. Seventy-eight per
      cent had severe and the remainder moderate ALRI (WHO classification). Clinical
      HIV infection was diagnosed in 219 (31%) children. One hundred and four children
      died, an overall case fatality rate (CFR) of 15%. In the clinically HIV-infected
      children, a CFR of 28% occurred, which constituted 60% of the overall ALRI
      mortality. A much lower CFR of 9% was found in the clinically non-HIV-infected
      children. Malnutrition, severe ALRI, age of 1 to 6 months, concurrent diarrhoea,
      duration of cough > or = 14 days and previous history of admission for ALRI were
      significant risk factors for mortality in ALRI. Low birthweight was not found to
      be a risk factor in this study. The impact of HIV infection on mortality in
      children with ALRI is of major concern in Zimbabwe and should be an important
      component of the national ALRI programme.

PMID- 7505551
TI  - Kawasaki disease in a Sudanese family.
AB  - Kawasaki disease (mucocutaneous lymph node syndrome) is an acute inflammatory
      multisystem disease of children. The acute phase of the disease is characterized
      by high grade fever, conjunctivitis, exanthematous skin rash and non-suppurative
      lymph node enlargement. The subacute phase follows with the manifestations of
      arthritis, myocarditis and thrombocytosis. The disease is self-limiting in most
      children but is associated with coronary artery aneurysms in 15-20% of cases. The
      aetiology is unknown, but results of epidemiological studies suggest that an
      unidentified infectious agent might be the causative factor. Since the first
      description of the disease by the Japanese doctor, Tomisaku Kawasaki, in 1967 and
      his report for the English literature in 1974, thousands of cases have been
      reported worldwide. The highest prevalence is found in Japan and among the
      Japanese in Hawaii, followed by the United States. Although the disease was first
      reported in Africa in 1979, to date only four cases have been reported there. The
      following account reviews the literature and describes the manifestations of
      Kawasaki disease as seen in two siblings in Khartoum, Sudan.

PMID- 7505552
TI  - Urinary stones in children in Zaria.
AB  - In a period of 16 years, 22 boys whose ages ranged from 10 months to 15 years
      were treated for stones occurring predominantly in the lower urinary tract. These
      boys represented 9.6/100,000 paediatric admissions, indicating the rarity of
      urinary stones in children in Zaria. Congenital obstructing lesions were present
      in 13 (59%) and the urine was infected in eight cases, most frequently by
      Klebsiella spp.

PMID- 7505553
TI  - Congenital malaria in a hyperendemic area: a preliminary study.
AB  - The prevalence of Plasmodium falciparum parasitaemia was evaluated in 59 neonates
      admitted to the University College Hospital, Ibadan in South-western Nigeria
      between August and December 1991--a period spanning part of both wet and dry
      seasons. Peripheral parasitaemia was present in 14 (23.7%) neonates; of these,
      four were preterm (4/26, 15%) and ten were term babies (10/33, 30.3%). The
      difference in the prevalence of P. falciparum parasitaemia in the two groups was
      not statistically significant (chi 2 = 1.78; p = 0.10). Parasite densities in all
      neonates were uniformly low (< 2000 asexual forms/microliters blood), and only
      four of the neonates had fever within 48 hrs of birth. Infected neonates weighed
      200 g more than non-infected neonates, but the difference was not statistically
      significant. Maternal weekly pyrimethamine prophylaxis did not appear to be
      effective in preventing infection as six (21.4%) of the 28 neonates whose mothers
      had regular prophylaxis had parasitaemia compared with seven (26.9%) of the 26
      neonates whose mothers had no prophylaxis (chi 2 = 0.22; p > 0.05). These data
      indicate that congenital malaria is not as uncommon as was previously thought and
      that the recent increase in reported cases may be due to an interplay of several
      factors.

PMID- 7505554
TI  - Severe illness caused by Rickettsia conorii.
AB  - An 18-month-old boy presented with a 5-day history of lethargy, fever, vomiting
      and rash. He required intensive care for inotropic and ventilatory support. He
      developed a disseminated intravascular coagulopathy and gangrene of his
      extremities. In addition, he had severe neurological dysfunction and loss of
      vision, both of which recovered spontaneously with time. The potential severity
      of tick typhus caused by Rickettsia conorii is described as well as the
      importance of paired serological tests in the diagnosis of this condition.

PMID- 7505555
TI  - Munchausen syndrome by proxy: an experience from Nigeria.
AB  - We report here on a child who over a period of 8 years was admitted several times
      to hospitals in different states of Nigeria based on fictitious illnesses
      described by his mother. The child had various unnecessary, expensive and
      invasive investigations followed by treatment with harmful drugs. The evolution
      of this case of Munchausen syndrome by proxy is described in order to alert
      paediatricians in developing countries to a problem which is described frequently
      in more affluent societies. We believe this is the first such case to be recorded
      in West Africa.

PMID- 7505556
TI  - Klebsiella septicaemia, osteomyelitis and septic arthritis in neonates in Ibadan,
      Nigeria.
AB  - An outbreak of skeletal infections associated with neonatal Klebsiella
      septicaemia seen over a 6-month period at the Special Care Baby Unit, University
      College Hospital, Ibadan is reported. It involved 12 neonates, and the
      significant antecedent events included perinatal asphyxia, fetal distress and
      prolonged rupture of membranes. All the babies had septic arthritis and ten cases
      had osteomyelitis in addition: multiple joint involvement occurred in 50% of
      cases. All the babies exhibited severe systemic disturbance and the Klebsiella
      isolated demonstrated multiple antibiotic resistance. The epidemic coincided with
      a period of severe water shortage which affected the hospital. The probable
      nosocomial acquisition of the infection is highlighted.

PMID- 7505557
TI  - Gastric teratoma: a case report.
AB  - Gastric teratoma is a very rare, usually benign, tumour of childhood. In
      industrialized countries, the diagnosis is facilitated by advanced technology
      when the infant is still in utero or soon after birth, and surgery is performed
      quite early in life, long before symptoms appear. This tumour was seen in our
      hospital in a 4-month-old boy. A mass had been noted at birth, but the infant
      remained symptomless. He was brought to hospital only on account of its rapid
      growth. The teratoma was successfully excised and the child was not seen again
      after discharge from hospital. We presume he remains well.

PMID- 7505558
TI  - The electrocardiographic changes in kwashiorkor.
AB  - An electrocardiogram (ECG), serum electrolytes, serum albumin, haematocrit and
      cardiothoracic ratio were recorded in 90 Nigerian children with kwashiorkor and
      90 age- and sex-matched controls. The ECG abnormalities observed among the study
      group included sinus tachycardia (91%), low QRS amplitude (100%) and prolonged
      QTc intervals (17%). Other ECG abnormalities noted were short QTc intervals
      (three children), prolonged PR intervals (four children) and right axis deviation
      (two children). The mean serum sodium, potassium, calcium, albumin, haematocrit
      and cardiothoracic ratio were significantly lower in children with kwashiorkor
      than in the controls (p < 0.001). The correlation between the QRS amplitude and
      serum potassium and calcium was poor (p > 0.05). Also, there was poor correlation
      between heart rate and haematocrit (p > 0.05) and between QTc intervals and serum
      calcium and potassium (p > 0.05). However, the correlation between the QRS
      amplitude and cardiothoracic ratio was good (r = 0.91, p < 0.001). These findings
      suggest that the ECG changes in kwashiorkor are due to myocardial atrophy.

PMID- 7505559
TI  - Laron dwarfism in the Arabian Gulf: a report of a sibship.
AB  - Laron dwarfism is a rare inherited form of short stature. Most cases reported
      have been in people of Mediterranean origin, particularly Oriental Jews. We
      describe the first sibship in an Arab Muslim family from Kuwait in the Arabian
      Gulf. This type of growth hormone insensitivity is caused by defects in the
      growth hormone receptor gene. The recently available recombinant human insulin
      like growth factor I has shown promise as a promoter of growth in children with
      Laron syndrome.

PMID- 7505560
TI  - Platelet function and hypothermic cardiopulmonary bypass.

PMID- 7505561
TI  - Interaction between neutrophils and endothelium.
AB  - The endothelial permeability associated with cardiopulmonary bypass in children
      is due, at least in part, to an inflammatory response. Neutrophils and their
      relationship with endothelium are fundamental to the production of capillary
      leak. This review discusses current concepts of the mechanisms involved in
      adhesion between neutrophils and the endothelium and its control. Evidence for
      modulation of these changes during bypass in children is reviewed. We have shown
      that cardiopulmonary bypass in children is associated with down-regulation (or
      shedding) of L-selectin and up-regulation of expression of CD11b/CD18. There may
      be a role for the cytokine interleukin-8 in the modulation of this process. We
      have demonstrated in vitro that certain of the procedures associated with bypass
      are associated with up-regulation of circulating neutrophil adhesion molecules
      and with the release of interleukin-8. These factors include changes in
      temperature and circulation. More research is required to tease out the most
      important components of the mechanisms of adhesion, and clinical correlations
      must be defined.

PMID- 7505562
TI  - Humoral and cellular activation in a simulated extracorporeal circuit.
AB  - Endothelial injury consequent upon widespread humoral and cellular activation is
      probably a major contributor to the phenomenon of cardiopulmonary bypass-induced
      organ dysfunction. This article reviews some of the mechanisms by which
      complement and neutrophil activation and interleukin-8 may be involved in this
      inflammatory response. In a model consisting of a simulated extracorporeal
      circulation we were able to demonstrate complement activation, profound and
      specific changes in neutrophil adhesion molecule expression, and interleukin-8
      generation. The importance of these changes and their potential interactions are
      discussed.

PMID- 7505563
TI  - Maintenance of clinical efficacy with finasteride therapy for 24 months in
      patients with benign prostatic hyperplasia. The Finasteride Study Group.
AB  - BACKGROUND: Finasteride, a 5 alpha-reductase inhibitor, has been shown to have
      beneficial effects in the treatment of benign prostatic hyperplasia. The long
      term safety and efficacy of finasteride in the treatment of benign prostatic
      hyperplasia was assessed. METHODS: In two multicenter, double-blind, placebo
      controlled studies (North American and international), patients with symptomatic
      benign prostatic hyperplasia were randomly assigned to receive finasteride, 1 or
      5 mg, or placebo for 1 year followed by an open-extension study in which all
      patients were treated with finasteride, 5 mg, regardless of original therapy. Men
      aged 40 to 80 years, in good physical and mental health, were eligible to enter
      the study. All patients were to have a maximum urinary flow rate of 15 mL/s or
      less with a voided volume of 150 mL or more, an enlarged prostate, and symptoms
      of urinary obstruction. Patients with a prostate-specific antigen level of 40
      mg/mL or more or any finding suggestive of prostate cancer were excluded.
      RESULTS: Two hundred ninety-eight patients received finasteride, 5 mg,
      continuously for 24 months. At the end of 24 months of finasteride therapy, the
      median prostate volume was reduced by 25%, and 60% of patients had a 20% or
      greater reduction in prostate volume. Maximum urinary flow rate was improved by
      at least 2 mL/s, and symptoms were improved by approximately 3.5 points.
      Decreased libido and ejaculation disorders were the only drug-related adverse
      experiences reported in more than 1% of patients. CONCLUSION: These studies
      support the long-term safety and tolerability of finasteride, while demonstrating
      its continuing clinical efficacy in the treatment of patients with symptomatic
      benign prostatic hyperplasia.

PMID- 7505564
TI  - A genetic and molecular study of learning processes in rats.
AB  - Using the conditioned feeding reflex model, a polymorphism for the rate of
      formation of this response was identified in a population of laboratory animals.
      Selection for high and low rate of the formation of this reflex resulted in
      significant differences in this character between two strains by the second
      generation. These differences were maintained in subsequent generations.
      Heterogeneity for the rate of the formation of conditioned response in the
      population is shown to be genetically determined. The RNA-dependent DNA
      polymerase activity in the hippocampus of fast-learning rats exceeds twofold that
      in slow-learning rats, while the rates of the DNA-dependent DNA-polymerase
      activities are similar. A significant increase in RNA-dependent DNA-polymerase
      only was found in the hippocampus of rats 20 min after training for the
      conditioned food response before the trace consolidation registered 40 min after
      the training session.

PMID- 7505565
TI  - A genetic, physiological, and biochemical investigation of audiogenic seizures in
      rats.
AB  - Two kinds of audiogenic seizures are characteristic of the KM rat strain,
      selected by Krushinsky and Molodkina in Moscow in the 1940s. This strain is now
      approximately 100% sound sensitive. Diallel crosses have demonstrated the
      polygenic nature of this behavior, with most alleles for seizures being
      recessive. Myoclonic seizures which develop after several sound exposures are a
      special form of kindling, involving the limbic system. Selection for low and high
      rates of myoclonic seizures was successful. Several unique, physiological
      features of the audiogenic seizures in this rat strain are described, as well as
      data on RNA and protein synthesis inhibition effects on seizure formation.

PMID- 7505566
TI  - Neurofibromatosis 1 mRNA expression in blood vessels.
AB  - Vascular hypertrophic lesions occur in neurofibromatosis type 1 (NF1). The role
      of the gene which causes NF1 in the growth and development of blood vessels is
      not known. mRNA expression of the NF1 gene was studied in blood vessels in the
      transition between intact and culture and in quiescent and proliferative
      conditions. The expression and alternative splicing pattern of the catalytic
      domain of NF1 consistently changed in proliferating cells, supporting a role for
      this gene in the regulation of growth of vascular smooth muscle and the vascular
      pathology in NF1.

PMID- 7505567
TI  - Synergistic control mechanism for abnormal site phosphorylation of Alzheimer's
      diseased brain tau by kinase FA/GSK-3 alpha.
AB  - When a synthetic peptide fragment (VAVVRTPPKSPSSAK) which corresponds to amino
      acid residues 226-240 from brain microtubule-associated protein tau was used as a
      testing substrate, we found that protein kinase FA/GSK-3 alpha was almost
      inactive towards this substrate. In sharp contrast, when Ser-10 of this peptide
      was replaced by a phosphoserine, the phosphopeptide fragment (VAVVRTPPKS(p)PSSAK)
      became an excellent substrate for kinase FA/GSK-3 alpha. Sequential manual Edman
      degradation together with phosphoamino acid analysis and protein sequencing
      further revealed that Thr-6 of the peptide fragment which corresponds to an
      important abnormal phosphorylation site Thr-231 in Alzheimer's diseased brain tau
      was the only site that was greatly phosphorylated, demonstrating that a pre
      phosphorylation becomes a prerequisite and is essential for promoting
      phosphorylation of Thr-231. Taken together, the results provide initial evidence
      that kinase FA/GSK-3 alpha mediates a synergistic phosphorylation control
      mechanism involved in the abnormal site phosphorylation of Alzheimer's diseased
      brain tau.

PMID- 7505568
TI  - Identification of the glycosylated sequons of human myelin-associated
      glycoprotein.
AB  - Myelin-associated glycoprotein (MAG) is a neural cell adhesion molecule
      expressing the L2/HNK-1 carbohydrate epitope. MAG is heavily glycosylated
      containing 30% carbohydrate by weight. In this study, human MAG glycopeptides
      were isolated and sequenced. Of the 9 MAG sequons 7 were glycosylated and 1 was
      partially glycosylated at Asn106. Asn332 which was not recovered in the
      glycopeptide fractions was probably not glycosylated. Furthermore, preliminary
      data indicate that all MAG glycosylated sequons might bear the L2/HNK-1 epitope.

PMID- 7505569
TI  - Insect immunity: the diptericin promoter contains multiple functional regulatory
      sequences homologous to mammalian acute-phase response elements.
AB  - We are using the diptericin gene as a model system to study the control of
      expression of the genes encoding antibacterial peptides during the Drosophila
      immune reaction. In order to investigate the putative regulatory regions in the
      diptericin promoter, we performed DNaseI footprinting experiments combined with
      gel-shift assays in two inducible systems: the larval fat body and a tumorous
      Drosophila blood cell line. Our results confirm the importance of kappa B-like
      elements previously described in the immune response of insects and reveal for
      the first time the involvement of other regions containing sequences homologous
      to mammalian acute-phase response elements.

PMID- 7505570
TI  - Effect of nitric oxide synthase substrate analog inhibitors on rat liver
      arginase.
AB  - Nitric oxide synthase (EC 1.14.23) substrate analog inhibitors NG-monomethyl-L
      Arg, NG-nitro-L-Arg, NG-nitro-L-Arg methyl ester, and aminoguanidine were
      examined as potential inhibitors of rat liver arginase (EC 3.5.3.1). NG-nitro-L
      Arg was found to inhibit arginase catalyzed conversion of L-Arg to L-Orn at pH
      7.5 with an IC50 = 27.2 +/- 4.3 mM, compared to L-Val and L-Lys with IC50 values
      of 6.2 +/- 0.4 mM and 31.3 +/- 2.7 mM, respectively. Inhibition was
      stereospecific for the L-amino acid, not NG-nitro-D-Arg, and required a free
      alpha-carboxyl group. NG-nitro-L-Arg was not a substrate for rat liver arginase.
      These results suggest that arginase inhibition should also be evaluated when
      studying the effects of NOS substrate analog inhibitors in vivo.

PMID- 7505571
TI  - Alcohol administration attenuates LPS-induced expression of inducible nitric
      oxide synthase in Kupffer and hepatic endothelial cells.
AB  - This study investigates the effects of in vivo ethanol (primed infusion, causing
      170-190 mg% plasma alcohol for 12 hours) and/or LPS (12 hours after injection of
      E. coli LPS 1 mg/kg bw.) on the mRNA expression of inducible nitric oxide
      synthase (NOS II) in hepatic cells measured by competitive PCR technique, and on
      hepatic release of reactive nitrogen intermediates (RNI, NO2- + NO3-). Perfused
      livers from alcohol- or saline-infused animals did not release measurable amounts
      of RNI. Under these conditions small amounts of NOS II mRNA were expressed in
      Kupffer and endothelial cells, while it was not detectable in parenchymal cells.
      LPS treatment along with markedly elevating hepatic RNI release increased NOS II
      mRNA levels by 35- and 200-fold, in endothelial and Kupffer cells, respectively.
      LPS injection and alcohol infusion to the same animal decreased hepatic RNI
      release by about 70% and almost completely inhibited the LPS-induced, elevated
      NOS II mRNA in Kupffer or endothelial cells. No similar changes were observed in
      the parenchymal cells. These data suggest that the primary target of in vivo LPS
      in upregulating hepatic NO release are the nonparenchymal cells. Furthermore,
      alcohol inhibits the LPS-induced response which may influence immune-related
      hepatic function.

PMID- 7505572
TI  - Cloning of a novel rat kidney cDNA homologous to CHIP28 and WCH-CD water
      channels.
AB  - Two kidney water channels have been identified: CHIP28 in proximal tubule and
      thin descending limb, and WCH-CD in collecting duct apical membrane. An
      homologous cDNA (WCH3) was obtained from rat kidney and found to encode a 276
      amino acid, 29 kDa protein with 39% amino acid identity to rat CHIP28, 50% to WCH
      CD and 49% to MIP26. The WCH3 transcript of 2.5 kb was expressed exclusively in
      kidney and was upregulated in dehydrated rats. Cell-free translation produced an
      approximately 28 kDa protein. Analysis of the predicted amino acid sequence
      indicated a hydrophobic protein with 4-6 membrane-spanning domains, with one N
      linked glycosylation site, two conserved NPA boxes common to MIP26 family
      proteins, and conserved residue C189 common to water channels. WCH3 is a new
      member of the MIP26 family of channel-forming proteins in mammalian kidney.

PMID- 7505573
TI  - Role of third N-terminal domain of VCAM-1.
AB  - The interaction between VLA-4 and VCAM-1 has been implicated in the recruitment,
      adhesion, and activation of mononuclear leukocytes in chronic inflammatory
      conditions and autoimmune disease. The seven domain extracellular portion of VCAM
      1, sVCAM1-7, and the first three and two N-terminal domains of VCAM-1, sVCAM1-3
      and sVCAM1-2, respectively, were expressed in baculovirus and purified. Using
      these purified soluble forms of VCAM-1 and cellular transfectants expressing
      various cell bound forms of VCAM-1, we show that the major binding site for VLA-4
      is located within the first two domains of VCAM-1 and that the third domain of
      VCAM-1 appears to be required for functional integrity of the VLA-4 binding site.

PMID- 7505574
TI  - Dexamethasone sensitizes soluble guanylate cyclase in the rat renal glomeruli.
AB  - We measured capability for guanosine 3',5'-cyclic monophosphate (cGMP) synthesis
      by isolated renal glomeruli from steroid-treated rats. Glomeruli obtained from
      animals treated with dexamethasone showed 5-fold higher sensitivity to sodium
      nitroprusside (SNP) than glomeruli from deoxycorticosterone- or saline-treated
      rats. Similar increase in activity of the glomerular soluble guanylate cyclase in
      response to SNP was observed. Dexamethasone markedly suppressed stimulatory
      effect of atrial natriuretic factor (ANF) on glomerular cGMP synthesis suggesting
      existence of cross-regulatory system(s) generating cGMP in renal glomeruli. We
      presume that glucocorticoid-induced hyperfiltration can be partially caused by
      sensitization of soluble guanylate cyclase to the nitric oxide, a potent natural
      dilatory agent.

PMID- 7505575
TI  - Concurrence between the molecular overlap regions in keratin intermediate
      filaments and the locations of keratin mutations in genodermatoses.
AB  - By analysis of the existing available data, we have found that the locations of
      disease-causing mutations in epidermal keratin genes are distributed in a non
      random manner. Most occur in exons 1 and 7 which encode the highly conserved 1A
      and 2B rod domain sequence regions of the keratin chains. Recent structural
      studies have suggested these sequences define an important overlap between
      neighboring molecules in keratin intermediate filaments. In order to better map
      the extent of these overlap sequences and concurrently to identify those
      sequences likely to be sensitive to mutations, we have used a series of synthetic
      peptides in an established filament disassembly assay. Thus residue positions 7
      16 of the 1A and positions 107-117 of the 2B rod domain segments describe the
      extent of the molecular overlap window wherein mutations in keratin (and perhaps
      other) intermediate filaments are most likely to alter filament stability and
      lead to abnormalities.

PMID- 7505576
TI  - Production and characterization of monoclonal antibodies to N-domain and domain
      III of carcinoembryonic antigen.
AB  - In order to obtain MoAbs against N-domain or domain III of carcinoembryonic
      antigen (CEA), mice have been immunized with a recombinant deleted CEA which was
      devoid of most of domains I and II. Of the nineteen MoAbs established, ten MoAbs
      were reactive with the N-domain of CEA, and others recognized the domain III. All
      Fab fragments of the MoAbs against the N-domain significantly inhibited
      homophilic cell adhesion mediated by CEA, whereas that of normal mouse IgG or
      control MoAb (anti-HLA class II) did not. Among the Fab fragments of MoAbs
      against the domain III, three inhibited the cell adhesion slightly, while five
      enhanced and one had no effect. These findings suggest that the N-domain of CEA
      plays an important role in the cell adhesion, and that the domain III is also
      involved in the binding. The MoAbs described in this study will be useful to
      elucidate the functional roles of the domains of CEA molecule.

PMID- 7505577
TI  - Rapidly-frozen polypeptide samples for characterization of high definition
      dynamics by solid-state NMR spectroscopy.
AB  - A method is described for defining anisotropic local dynamics in polypeptides by
      solid-state NMR. To avoid conformational heterogeneity introduced by large
      hexagonal ice crystals in low temperature hydrated samples, a fast-freezing
      technique is used for sample preparation. For a demonstration of this approach,
      the backbone librational motions of the gramicidin A channel conformation are
      studied in hydrated DMPC bilayers. The static 15N chemical shift tensor is
      characterized at 123 K for the Ala3 site. The temperature dependence of this
      tensor yields a determination of the librational amplitude and anisotropy of the
      motionally sampled space. This amplitude represents the sum of nanosecond and
      picosecond time-frame motions, both of which have a significant amplitude.

PMID- 7505578
TI  - cDNA cloning of a putative protochordate FK506-binding protein.
AB  - A tunicate (Botryllus schlossert) cDNA library was screened with a microsatellite
      probe. Five positive clones were sequenced, each with a 5' truncated
      microsatellite. One (Bs.6) revealed striking similarity to FK506 and rapamycin
      binding proteins (FKBPs). Clone Bs.6 is 500 base pairs long and encodes for a
      putative protein of 134 amino acids. The predicted protein features the two FKBP
      type peptidyl-prolyl cis-trans isomerase (PPIase) signatures and an endoplasmic
      reticulum retention signal. This protochordate protein is substantially similar
      to 12-13 kDa FKBPs, most remarkably to one of the receptors that had been
      proposed to mediate the immunosuppressive actions of FK506, the human FKBP-13
      (62% amino acid identity and 74% similarity).

PMID- 7505579
TI  - Steel factor and granulocyte-macrophage colony stimulating factor act together to
      enhance choline-lipid turnover during synergistically stimulated proliferation of
      the human factor dependent cell line, M07E.
AB  - The hematopoietic growth factors granulocyte-macrophage colony stimulating factor
      and steel factor have been shown to synergize in the stimulation of proliferation
      of the human factor-dependent cell line M07e. We investigated the possible
      involvement of lpid-mediated signaling in granulocyte-macrophage colony
      stimulating factor and steel factor induced proliferative synergism. It was found
      that treatment of M07e cells with these factors alone stimulates choline lipid
      metabolism and that they cooperate to further enhance this effect. Therefore a
      choline lipid signal transduction pathway may operate as part of the series of
      events leading to synergistic growth induced by the combination of granulocyte
      macrophage colony stimulating factor and steel factor.

PMID- 7505580
TI  - Regulated secretory proteins in the exocrine pancreas aggregate under conditions
      that mimic the trans-Golgi network.
AB  - Fifteen pancreatic secretory proteins, including seven serine-endoproteinases
      (isoenzyme forms of trypsinogen, chymotrypsinogen and proelastase), four metallo
      exoproteinases (isoenzymic forms of procarboxypeptidase A and procarboxypeptidase
      B), amylase, lipase, and two forms of carboxyl ester lipase were observed to
      aggregate under conditions of acidic pH (5.5) and calcium that mimic the trans
      Golgi network. Subsequent neutralization of the pH resulted in disruption of
      protein aggregates and solubilization of pancreatic (pro)enzymes. In the absence
      of secretory granule membranes, granule contents display an "intrinsic" property
      for reversible, pH-dependent aggregation under conditions of mild acidification.

PMID- 7505581
TI  - Inhibitory effect of bisbenzylisoquinoline alkaloids on nitric oxide production
      in activated macrophages.
AB  - Bisbenzylisoquinoline (BBI) alkaloids are anti-inflammatory constituents of
      plants of the families Menispermaceae and Ranunculaceae, which have been used as
      folk remedies in Japan and China. Five BBI alkaloids (cepharanthine,
      chondocurine, cycleanine, isotetrandrine and tetrandrine) were tested for
      suppressive effect on in vitro nitric oxide (NO) production by lipopolysaccharide
      stimulated peritoneal macrophages, which were induced with thioglycollate or
      bacillus Calmette-Guerin in mice. All these BBI alkaloids significantly
      suppressed NO production at 5 micrograms/mL. Cepharanthine, isotetrandrine and
      cycleanine were slightly more inhibitory than tetrandrine and chondocurine. The
      suppression persisted for at least 48 hr. As NO is one of the critical mediators
      in inflammation, these results may explain some aspects of the anti-inflammatory
      mechanisms of BBI compounds.

PMID- 7505582
TI  - Protective effect of various calcium antagonists against an experimentally
      induced calcium overload in isolated hepatocytes.
AB  - The effect of the hepatotoxic substance diamidinothionaphthene (98/202) on
      cytosolic, mitochondrial and extra-mitochondrial calcium distribution was
      measured in isolated rat hepatocytes. The drastic disturbance of the
      intracellular calcium homeostasis caused by this substance (increase of the
      cytosolic and mitochondrial calcium contents and depletion of extra-mitochondrial
      calcium stores, which at last lead to cell death) gave rise to an investigation
      of the possible cytoprotective effect of calcium antagonists of various chemical
      classes: verapamil, diltiazem, and nifedipine on isolated hepatocytes. Our
      results show that all three calcium antagonists prevented cell death caused by
      98/202. The 98/202-induced increase of cytosolic and mitochondrial calcium
      content was inhibited by all three calcium antagonists. However, only verapamil
      was able to inhibit the depletion of extra-mitochondrial calcium stores. Since
      98/202-induced cell death occurs only in the presence of extracellular calcium,
      it is concluded that calcium antagonists are also able to inhibit the influx of
      extracellular calcium in liver cells, which leads to a calcium overload of the
      cytosol and mitochondria. The various ways of interfering with the calcium
      homeostasis of liver cells qualifies the hepatotoxic substance 98/202 as a
      suitable in vitro hepatotoxicity model for testing the hepatoprotective effect of
      different calcium antagonists.

PMID- 7505583
TI  - Dissociation of xanthine oxidase induction and cytochrome P450 depression during
      interferon induction in the rat.
AB  - Interferon (IFN) and IFN inducers down-regulate hepatic cytochrome P450 (P450)
      through a pretranslational mechanism involving depression of P450 mRNA levels and
      a subsequent decrease in P450 synthesis. Current evidence suggests that
      interferon induces the synthesis of a protein which subsequently mediates the
      down-regulation of P450. Xanthine oxidase (XO) activity is induced by interferons
      in rodents, and the XO inhibitor allopurinol (AP) inhibits the down-regulation of
      P450 by interferons in the mouse and hamster so it has been proposed as the
      putative intermediate protein. In studies undertaken in rats to further
      characterize the molecular basis of the protective effect of AP, we observed that
      AP (20 and 50 mg/kg) did not protect against down-regulation of P450 by the
      interferon inducer polyinosinic-polycytidylic acid (10 mg/kg). In fact, at 50
      mg/kg AP had an additive effect on the depression of CYP2E1. Total XO induction
      in the rat was only 30-50% compared with 100-500% in mice and hamsters, and this
      induction was inhibited completely by AP. Therefore, XO does not mediate the down
      regulation of hepatic cytochrome P450 by interferons in the rat.

PMID- 7505584
TI  - Influence of dihydropyridine-type calcium agonists on hemodynamics and myocardial
      ischemia in isolated rabbit hearts.
AB  - Calcium (Ca) agonists like Bay k 8644 ((-)-S-1,4-dihydro-2,6-dimethyl-3-nitro-4
      (2-trifluoromethylphenyl) pyridine-5-carboxylate (CAS 93468-89-4), may represent
      a new principle in the treatment of heart failure. Because of marked
      vasoconstrictive properties, these agents may have a deleterious effect on
      myocardial ischemia (MI). It was however demonstrated that contractility
      enhancement and coronary flow (CF) reduction do not automatically enlarge MI.
      Therefore, we investigated the influence of Bay k 8644 (10(-8) mol/l) in
      comparison to ouabain (1.5 x 10(-7) mol/l) in non-arrhythmogenic concentrations
      on MI in electrically paced isolated rabbit hearts (Langendorff, constant
      pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l, 180 beats/min). MI was
      induced by coronary artery ligation and quantified by epicardial NADH
      fluorescence. Left ventricular pressure (LVP) was significantly increased by
      ouabain (+10-20%) but slightly diminished by Bay k 8644 (-10%) (p < 0.05). CF
      reduction after Bay k 8644 (-30%) was more pronounced than after ouabain (-10%)
      (p < 0.05), but both substances did reduce relative CF (CF/LVP x heart rate) to
      the same extent (-20-30%) (p > 0.05). Nevertheless, ouabain did not significantly
      influence epicardial NADH-fluorescence area or intensity (p > 0.05), whereas MI
      was significantly enlarged by Bay k 8644 (+30%) (p < 0.05). It is concluded that
      in isolated rabbit hearts ouabain and Bay k 8644 might influence CF-distribution
      differently with a more pronounced diminuation of the nutritive CF induced by Bay
      k 8644.

PMID- 7505585
TI  - 4-Quinolone bactericidal mechanisms.
AB  - The bactericidal activity of nalidixic acid against Escherichia coli strain KL16
      in nutrient broth was abolished by the addition of rifampicin. Cells suspended in
      phosphate-buffered normal saline (PBS) were also not killed by nalidixic acid.
      Experiments with modern 4-quinolones showed their activities varied according to
      the conditions under which they were tested. Rifampicin did not affect the
      concentration at which ofloxacin became bactericidal in nutrient broth, but did
      limit the extent of ofloxacin-induced death. However, rifampicin produced a 10
      fold increase in the concentration at which ciprofloxacin became bactericidal in
      nutrient broth, and completely abolished the bactericidal activity of
      norfloxacin. Unlike nalidixic acid all of the modern 4-quinolones killed cells
      suspended in PBS. Based on these results it was possible to differentiate 3
      processes by which 4-quinolones induced death. Mechanism A was only active
      against dividing bacteria and required RNA and protein synthesis; it was
      therefore not active against bacteria suspended in PBS and was inhibited in
      nutrient broth by the addition of rifampicin. Mechanism B required neither RNA
      nor protein synthesis and was also active against non-dividing bacteria; it was
      therefore not inhibited by rifampicin nor by suspending bacteria in PBS.
      Mechanism C killed non-dividing bacteria, but required protein and RNA synthesis:
      it therefore functioned in PBS, but was inhibited by rifampicin.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7505586
TI  - Evaluation of possible histamine release from human peripheral blood cells using
      an enzyme immunoassay (HRT) with components of intravenous catheters.
AB  - The HRT Assay was evaluated for its capacity to measure histamine release from
      blood basophils following the introduction of extracts from catheters made of
      Aquavene or silicone. Blood samples were collected from twenty-one volunteers of
      the University of California, Davis campus and from seven individual who had
      experienced a systemic event during the insertion of catheters made from
      Aquavene. None of the blood samples released histamine in quantities that would
      be anticipated in an anaphylactic or anaphylactoid reaction when challenged with
      the extracts; all released histamine when challenged with polymyxin B, used as a
      positive control. Based upon these results, none of the components of either the
      Aquavene-based or silicone-based catheters are thought to cause a histamine
      associated reaction in subjects. This assay proved to be both expedient and
      reliable in its determination of the release of histamine from blood basophils.

PMID- 7505587
TI  - Prenatal diagnosis of cystic fibrosis in different European populations:
      application of denaturing gradient gel electrophoresis.
AB  - The cystic fibrosis transmembrane regulator gene, one of the most commonly
      mutated in the European population, was cloned in 1989 and since then has been
      extensively analysed in patients of various ethnic backgrounds. We have screened
      the entire coding sequences of the cystic fibrosis transmembrane regulator gene
      and identified many mutations and polymorphisms. In this paper we propose a
      general strategy to improve prenatal diagnosis and genetic counselling of cystic
      fibrosis (CF). As this approach based on denaturing gradient gel electrophoresis
      is adaptable to different populations, it greatly increases the sensibility and
      specificity of CF prenatal diagnosis.

PMID- 7505588
TI  - Comparison of four grass pollen species concerning their allergens of grass group
      V by 2D immunoblotting and microsequencing.
AB  - The identification and characterization of allergenic components is a vital step
      towards improving diagnosis and therapy. Members of the grass family (Poaceae)
      reveal a high cross-reactivity among each other caused by the close
      phylogenetical relationship. In order to investigate the variability between
      allergenic components, we studied the allergen grass group V, one of the major
      allergens. Pollen extracts of 4 different tribes (timothy grass (Phleum pratense)
      -Agrostidae, perennial rye grass (Lolium perenne)--Festuceae, meadow velvet
      (Holcus lanatus)--Aveneae, and rye (Secale cereale)--Triticeae) of the
      Festucoideae subfamily were separated by 2D PAGE and investigated by
      immunoblotting using patients' poolserum and monoclonal antibodies (raised
      against group V allergens of timothy grass pollen). The antibodies identify
      different allergens in the four grass species. The components vary from 30-50 kDa
      and pI 4.8-7.0. The eight NH2-terminal amino acids were determined and indicated
      high similarities between the different components. These results cast doubt on
      the suitability of classifying allergens into groups based only on their
      molecular mass, isoelectric point and N-terminal sequence analysis. It suggests
      to classify allergens according to their IgE-reactive epitopes.

PMID- 7505589
TI  - Human leucocyte elastase (HLE) preferentially cleaves the heavy chain H2 of inter
      alpha-trypsin inhibitor (ITI).
AB  - Inter-alpha-trypsin inhibitor (ITI) is a complex protein containing two heavy
      polypeptide chains (H1 and H2) and a light chain, which in the free state is
      known as bikunin. In vitro cleavage of ITI with different proteases releases
      bikunin, but does not abolish the antitryptic activity. To study the mechanism of
      bikunin release, ITI was incubated with human leucocyte elastase (HLE). The
      resulting ITI fragments were characterized by (i) their electrophoretic and
      chromatographic behavior. (ii) their immunological reactivity towards antibodies
      specific for each of the heavy chains H1 and H2, and (iii) their N-terminal
      sequences. Our results demonstrate that the H2 heavy chain of ITI is particularly
      sensitive to HLE, and that early cleavage products (M(r)-values 120-150,000)
      consist of H1 linked to bikunin. A scheme is proposed for the mechanism for ITI
      degradation.

PMID- 7505590
TI  - Trigeminal nerve section for chronic migrainous neuralgia.
AB  - We report a series of 14 patients who underwent partial or complete trigeminal
      nerve root section for chronic unremitting migrainous neuralgia. They had all
      suffered attacks with severe pain for over 18 months without remission (mean
      duration 5.5 years). Symptoms were refractory to extended medical intervention
      and had caused prolonged disruption of lifestyle. The sensory root was completely
      divided in two cases with complete relief of pain (mean follow-up period 5.6
      years). In the other 12 patients, 50-90% of the superomedial portion of the
      sensory root was divided. Of these, five received no further surgery, and
      experienced complete (n = 2), near complete (n = 2), or incomplete (n = 1) relief
      of neuralgia (mean follow-up 5.5 years). The remaining seven patients in the
      partially divided group were not relieved of pain after operation (n = 5) or
      suffered early recurrence of pain (n = 2). They showed incomplete sensory loss in
      the first trigeminal division (V1) and had a second operation to extend the nerve
      division. V1 anaesthesia was established in all cases after the second procedure,
      and as a result, four are currently completely free of pain and one has near
      complete relief of pain. The remaining two patients are still experiencing severe
      neuralgia (mean follow up 4.1 years). Twelve out of 14 patients (85.7%) receiving
      surgery for chronic migrainous neuralgia experienced adequate pain relief and are
      able to follow a normal life (mean follow up 5.6 years). Corneal abrasion was the
      commonest long-term complication, occurring in three cases (28.5%) and
      progressing to chronic keratitis in one. We conclude that total trigeminal nerve
      root section is an effective treatment for patients suffering from chronic
      migrainous neuralgia and can be safely offered as a primary surgical treatment.

PMID- 7505591
TI  - Cerebrovascular changes following administration of gammaglobulins against
      substance P or calcitonin gene related peptide in monkey with subarachnoid
      haemorrhage.
AB  - Cerebrovascular changes after intrathecal (ith) administration of gammaglobulins
      against substance P (SP) or calcitonin gene-related peptide (CGRP) were
      investigated before and following a simulated subarachnoid haemorrhage (SAH) in
      the squirrel monkey. The SAH was produced by injection of homologous blood into
      the interpeduncular fossa and the cisterna magna. The gammaglobulins were given
      both prior to the blood injections and daily in 5 days post-SAH. The effect of
      the gammaglobulins was examined by angiography pre-SAH and at 10 min and at 6
      days post-SAH, i.e. the time points for maximal acute and late spasm in the
      present model. Cerebral blood flow (CBF) was measured under general anesthesia at
      day 6 post-SAH with an autoradiographic technique. Five of nine animals treated
      with CGRP antigammaglobulin died from respiratory failure. Four animals received
      SP antigammaglobulin and two control animals received normal globulin. SP
      antigammaglobulin per se had no effect on baseline arterial diameter, while CGRP
      antigammaglobulin significantly reduced the diameter of the arteries. SP
      antigammaglobulin prevented the occurrence of acute spasm and significantly
      reduced the degree of late spasm. Moreover, the reduction in CBF noted in the
      control SAH animals was significantly reduced. In contrast, CGRP
      antigammaglobulin treatment had no effect on the degree of spasm and did not
      cause any change in CBF as compared to controls. The finding that CGRP but not SP
      antigammaglobulin significantly reduces the arterial diameter in conjunction with
      our previous demonstration that a post-, but not preganglionic trigeminal lesion
      reduces the baseline arterial diameter, indicates that CGRP could be the
      transmitter involved in a peripheral axon reflex. The function of SP might be as
      a neurotransmitter conveying information to the brainstem. The transmitter role
      is supported by the effect of SP antigammaglobulin impairing SP containing
      neurons and, in that way, mimicking a bilateral trigeminal rhizotomy.

PMID- 7505592
TI  - Corpus callosum agenesis in two male infants of a heterozygotic triplet
      pregnancy.

PMID- 7505593
TI  - Increased platelet reactivity to prostaglandin E1 in hypertension is linked with
      altered signal transduction.
AB  - Prostaglandin E1 has been shown to induce a greater accumulation of cAMP in
      platelets from spontaneously hypertensive (SHR) than in platelets from
      normotensive (Wistar-Kyoto, WKY) rats (Circ. Res. 1978;43:583-591. Thromb. Res.
      1988;49:5-21). This study was conducted to determine the mechanisms of increased
      platelet reactivity to PGE1 in hypertension. The number of PGE1 binding
      sites/platelet (WKY 280 +/- 8, SHR 287 +/- 5) as well as the Kd for WKY (105 +/-
      11 nmol/L) and SHR (120 +/- 14 nmol/L) were found to be similar in WKY and SHR
      rats. PGE1-induced GTPase activity was determined using WKY and SHR platelet
      membranes. The basal GTPase activity was similar in WKY and SHR platelets.
      Incubation of membranes with PGE1 (3 mumol/L) for 1 min increased GTPase activity
      by 46% in WKY and by 806% in SHR. Incubation of platelets with 1.0 mmol/L IBMX (3
      isobutyl-1-methyl-xanthine) for 4 min resulted in a 327 +/- 57% and 320 +/- 11%
      increase in cAMP in WKY and SHR platelets, respectively. In other experiments,
      incubation of platelets with 3, 10 and 100 mumol/L forskolin, induced similar
      increases in cAMP levels in WKY (103 +/- 12%, 530 +/- 42%, 784 +/- 41%) and SHR
      (111 +/- 13%, 461 +/- 18%, 756 +/- 28%) platelets. These data lead us to suggest
      that the greater accumulation of cAMP induced by PGE1 in SHR than in WKY
      platelets is linked with altered PGE1-receptor mediated signal transduction at
      the G-protein level.

PMID- 7505594
TI  - A simple method to determine the enantiomeric ratio in enantioselective
      biocatalysis.
AB  - The enantiomeric ratio (E) is commonly used to characterize the
      enantioselectivity in enzyme-catalyzed kinetic resolution. In this paper this
      parameter is directly derived from the enantiomeric excess of substrate and
      product. This is formally more correct than using Chen's equation after
      calculating the degree of conversion from both ee values using the relation of
      Sih and Wu. New expressions and useful graphs have been generated for reversible
      and irreversible uni-uni reactions. The theoretical predictions have been
      verified experimentally for various reactions. Values for E and the thermodynamic
      equilibrium constant, KEQ, were obtained for a (DL)-dehalogenase-catalyzed
      dehalogenation, a hydrolysis reaction by porcine pancreatic lipase, and for C.
      Cylindracea lipase-catalyzed esterification and transesterification. In view of
      the current developments in the field of chiral analysis, this method is an
      easily available tool in the quantitative treatment of enzyme-catalyzed
      resolution of enantiomers.

PMID- 7505595
TI  - Diffusion of sucrose and dextran through agar gel membranes.
AB  - Mass transfer limitations severely impede the performance of bioreactions
      involving large molecules by gel-entrapped microorganisms. This paper describes a
      quantitative investigation of such diffusional limitations in agar gel membranes.
      Sucrose and commercial dextran fractions with (weight-average) molecular weights
      ranging from 10,000 to 2,000,000 Da were used as standard diffusants. For all
      tested solutes but sucrose, the values of the agar/water partition coefficients
      highlighted steric hindrance at the entrance of the membrane pores. The effective
      diffusivity of sucrose in agar was similar to that in water. All dextran
      fractions, however, displayed restricted diffusion in the agar membranes. Their
      effective diffusivities were a decreasing function of the agar content of the gel
      membrane (0.5, 1.0, or 1.5% w/v). The effective diffusivity in a given membrane
      decreased as the molecular weight of the diffusing molecule increased. T500 (Mw =
      470,000 Da) and T2000 (Mw = 1,950,000 Da) fractions were unable to diffuse
      through 1.0 or 1.5% agar membranes. The diffusion data did not agree with the
      classical (Renkin) model for a hard sphere diffusing through a cylindrical pore.
      These results are discussed in terms of gel and diffusant characteristics.

PMID- 7505596
TI  - The DIG (digoxigenin) shift assay.

PMID- 7505597
TI  - Rapid nonradioactive detection of HIV-1 RNA from a single-cell equivalent by
      reverse transcription PCR with nested primers.

PMID- 7505598
TI  - Radioanalytic estimation of amplification products generated by reverse
      transcription PCR using [alpha-33P] deoxyribonucleoside triphosphate.

PMID- 7505599
TI  - A rapid nuclear runoff transcription assay.

PMID- 7505600
TI  - Direct RT-PCR amplification of mRNA supported on membranes.
AB  - We describe a simple and efficient technique that facilitates the amplification
      of specific mRNA for cloning and sequencing purposes. An mRNA bound to a small
      piece of membrane filter is used as a template to synthesize complementary DNA.
      The product of this reaction is then transferred to a new tube and amplified
      using a standard PCR protocol. By simple enzymatic treatment, this RNA membrane
      can be reused as many times as needed with no problems of low yield, mispriming
      or background. Multiple advantages and different applications can be gained with
      this procedure. We have been using this technique to characterize a 4.5-kb mRNA
      from human retinal pigment epithelial cells following identification by Northern
      blot. According to the size of the PCR amplification products, this mRNA band
      contains portions of the coding sequence for the Na+K(+)-ATPase beta 1 subunit.

PMID- 7505601
TI  - A method for the amplification of unknown flanking DNA: targeted inverted repeat
      amplification.
AB  - A new method has been developed that permits the rapid amplification of unknown
      DNA flanking a known site so that one can walk into an uncharacterized region of
      DNA. This method eliminates the steps and sequence artifacts associated with
      cloning and permits genome walking into unclonable regions of DNA. In this
      method, human genomic DNA is restriction enzyme digested and then ligated to the
      3' end of a 5'-phosphorylated oligonucleotide using a short bridging
      oligonucleotide using a short bridging oligonucleotide as a splint. The
      phosphorylated oligonucleotide is designed to create 5'-end extensions that are
      complementary to the known sequence. Following denaturation and reannealing under
      dilute conditions that promote intra-strand annealing and under high stringency,
      only those DNA strands that contain the known sequence will form a stem-loop
      structure with a recessed and phosphorylated 5' end. This stem-loop renders a
      substrate for a subsequent heat-stable ligation reaction to another
      oligonucleotide that anneals to the known sequence immediately adjacent to the
      phosphorylated oligonucleotide high-stringency annealing site. The
      oligonucleotide appended to the phosphorylated oligonucleotide by the heat-stable
      ligase can, when present in its free, non-ligated form, prime DNA polymerase
      mediated amplification of those strands modified by site-specific ligation to
      this same oligonucleotide. This is followed by one or two nested DNA
      amplifications, with the final amplification primed by the phosphorylated
      oligonucleotide in its free, non-ligated form. We successfully applied this
      method to the specific amplification of 2.2 kb of DNA flanking the 5' end of the
      cystic fibrosis transmembrane conductance regulator cDNA using primers that
      anneal to the cDNA sequence and to the specific amplification of 2.2 kb of human
      genomic beta-globin DNA flanking the primer annealing sites.

PMID- 7505602
TI  - Panning transfected cells for electrophysiological studies.
AB  - Panning was used to select co-transfected cells expressing plasmid-encoded ion
      channels. Adherent cells were cotransfected by the CaPO4 method with a plasmid
      encoding a cell surface marker (CD8) along with another plasmid encoding an ion
      channel. At 1-3 days post-transfection, the cells were suspended, treated with a
      biotinylated CD8-specific antibody and placed into streptavidin-coated bacterial
      petri dishes. After 2 h, these dishes were washed with a saline solution to
      remove cells that did not adhere to the streptavidin-coated dishes. By using
      molar ratios of > or = 8:1 of the ion channel encoding plasmid to the CD8
      plasmid, we found that > or = 50% of the panned cells that adhered to coated
      dishes were positive for expression of the co-selected gene. Cells expressing
      plasmid-encoded channels (voltage-dependent sodium channels or cystic fibrosis
      transregulator chloride channels) were assayed using whole-cell recording,
      perforated-patch recording and single-channel recording. The method was tested on
      tsA201 and NIH3T3 cells, the latter of which transfected very poorly (usually <
      4% efficiency) with our standard protocols. When the co-selected plasmid encoded
      the bacterial beta-galactosidase gene, it was possible to determine by
      histological assay the percentage of positively transfected cells (with and
      without panning). Panning in some cases increased the percentage of positively
      cotransfected cells by more than 20-fold. This technique is particularly useful
      when selecting co-transfected cells for electro-physiological recordings on
      individual cells.

PMID- 7505603
TI  - Fast chemiluminescent measurement of RNA polymerase activity based on photon
      counting technology.
AB  - A fast and simple assay for T7 RNA polymerase based upon chemiluminescent
      detection of the synthesized, digoxigenin-labeled RNA on a nylon membrane with
      anti-digoxigenin coupled alkaline phosphatase and CSPD as substrate is described.
      Activity of RNA polymerase is determined with high sensitivity by quantifying the
      emitted light of the microplate-formatted dot-blot membrane with a photon
      counting microplate luminometer and a specially designed filter adapter. The
      described method is one example for the application of this new adapter to
      measure luminescent membrane filters.

PMID- 7505604
TI  - Rapid fluorescence quantitation of plasmid miniprep DNA.

PMID- 7505605
TI  - Differentiation of heterogeneous phenotypes in human osteoblast cultures in
      response to 1,25-dihydroxyvitamin D3.
AB  - 1,25(OH)2D3 (1,25-dihydroxyvitamin D3) inhibits the cell proliferation of human
      osteoblast-like cell cultures, but stimulates the synthesis of two of the
      phenotypic markers of the osteoblast, alkaline phosphatase and osteocalcin. It is
      not known whether all cells which synthesize alkaline phosphatase also synthesize
      osteocalcin in response to 1,25(OH)2D3. In this study we addressed this question
      by examining the response of human osteoblast-like cell cultures to 1,25(OH)2D3,
      using concurrent histochemical and immunochemical staining for alkaline
      phosphatase and osteocalcin, respectively. The cells were grown in the presence
      or absence of 1,25(OH)2D3 (10(-9) M) for 48 h. Co-localisation of osteocalcin and
      alkaline phosphatase in osteoblast-like cell cultures showed that not all cells
      which synthesize osteocalcin (about 9%) in response to 1,25(OH)2D3 synthesize
      alkaline phosphatase (about 24%) and vice versa. There was also a proportion of
      osteoblast-like cells which produce both osteocalcin and alkaline phosphatase
      simultaneously (about 12%). These findings suggest that during differentiation of
      bone-derived cells in cultures, in response to 1,25(OH)2D3, heterogeneous
      phenotypes with respect to expression of alkaline phosphatase and osteocalcin
      appear.

PMID- 7505606
TI  - Visualisation and selective elimination of a subpopulation of mitogen-responsive
      bone marrow stromal cells using bromodeoxyuridine and photo-induced cell killing.
AB  - Porcine bone marrow stromal cells (PBMSC) are a source of skeletogenic
      mesenchymal progenitor cells. Unfortunately, the heterogeneous nature of these
      cells in culture complicates the interpretation of their growth-factor
      responsiveness. We have therefore pulse-labelled mitogen-stimulated PBMSC with
      bromodeoxyuridine (BrdU) in order to study individual, growth-factor responsive
      cells in the presence of large numbers of nonresponsive PBMSC. Transfer of
      growing cells to low serum medium reduced BrdU labelling from 35% to 4% over a
      period of 24 hours. Subsequent addition of foetal calf serum (FCS) to serum
      arrested cultures increased the number of BrdU positive cells to 54% by 16 hours.
      Addition of basic fibroblast growth factor (bFGF) to serum-arrested cultures
      induced DNA synthesis in 28% of cell by 16 hours after stimulation. In order to
      selectively eliminate mitogen responsive cells from mixed cultures, BrdU
      substituted cells were photosensitised with bisbenzimide and exposed to bright
      light. BrdU-labelled PBMSC died within 20-40 hours of bisbenzimide treatment and
      subsequent illumination, whereas BrdU-labelled cells survived in the dark despite
      treatment with bisbenzimide. The photokilling procedure appeared to have no long
      term effect upon the viability of non-BrdU-labelled cells because if subconfluent
      cells were brought to serum arrest prior to photokilling, no change in DNA
      content relative to controls was observed after a subsequent 4 or 7 day
      incubation in Dulbecco's modified Eagle's medium (DMEM)/10% FCS.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7505607
TI  - Treatment of postdural puncture headache with 'epidural dextran patch'.

PMID- 7505608
TI  - Epidural dextran for PDPH.

PMID- 7505609
TI  - Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte
      chemotactic peptide receptors.
AB  - Several cDNA clones encoding receptors for leukocyte chemoattractants, including
      IL-8, C5a, N-formyl peptides (FP), and platelet-activating factor, have been
      isolated in the past 3 years. The primary structure of these receptors revealed
      that they are members of the superfamily of G protein-coupled receptors
      containing seven transmembrane domains. In this study the polymerase chain
      reaction was carried out to isolate novel cDNA clones encoding human receptors of
      IL-8 related cytokines, chemokines, from a human monocyte cDNA library using
      degenerate oligonucleotide primers devised from conserved sequences among the
      cDNAs encoding the human receptors for IL-8, FP and C5a. Four novel cDNA clones
      (HM63, HM74, HM89, and HM145) in addition to cDNAs for FP and C5a receptors were
      isolated. All polypeptides encoded by the cloned cDNAs share common features with
      the G protein-coupled receptor superfamily, such as seven putative hydrophobic
      transmembrane domains and, except for HM74, N-linked glycosylation sites near the
      N-terminus. The amino acid sequence identities among HM63, HM89, HM145, IL-8
      receptors, FP receptor, and C5a receptor are in the range of 24-68%, higher than
      those of other members of the G protein-coupled receptor superfamily. Moreover,
      the number of amino acids between the fifth and sixth transmembrane domains,
      which varies within this superfamily, is the same in these receptors. Thus, three
      of the newly identified proteins probably belong to a 'leukocyte chemotactic
      peptide receptor family'. HM74 differs from the other clones with respect to the
      amino acid homology, suggesting that this may be the receptor for a different
      type of ligand. Furthermore, it was confirmed that HM145 is a functional receptor
      for LD78, one of the C-C chemokines, as revealed by the measurement of decrease
      of cAMP accumulation as well as calcium influx using stable transfectants.

PMID- 7505610
TI  - Phenotypic and functional heterogeneity of the IgD- B cell compartment:
      identification of two major tonsillar B cell subsets.
AB  - Two major B cell subpopulations were identified in the IgD- compartment of
      tonsils and subsequently isolated. They displayed the following phenotypes:
      CD10+CD38+CD44- (CD38+ B cells) and CD10-CD38-CD44+ (CD38- B cells). Of the CD38-
      B cells, 70% also expressed CD24 and CD39, whereas CD77 was specifically
      distributed on 40% of CD38+ B cells, suggesting an additional level of
      heterogeneity in the cellular composition of these two B cell types. Whereas the
      majority of CD38+ B cells were in cycle, most CD38- B cells were quiescent.
      Conversely, Bcl-2 was expressed in CD38- B cells but was not detected in CD38+ B
      cells. Of the CD38- B cells, 30% bore the homing receptor Leu-8/Mel-14, whereas
      CD38+ B cells lacked this marker. Thus, CD38- B cells have both survival capacity
      and migratory competence. Both subsets expressed surface (s) Igs which were
      mainly of the IgG class, implying that most of these cells have already undergone
      isotype switching. CD38- B cells proliferated vigorously and produced large
      amounts of IgG in response to cytokines, following ligation of slgs or CD40. In
      contrast, CD38+ B cells were only stimulated for DNA synthesis by a combination
      of IL-4 and anti-CD40 antibodies, and failed to differentiate into Ig-secreting
      cells regardless of the stimulus applied. We propose that CD38- B cells represent
      an extra-follicular mature B cell population which has been positively selected
      and rescued from apoptosis, whereas the CD38+ B cell subset is composed of
      germinal centre B cells.

PMID- 7505611
TI  - Correction of gld autoimmunity by co-infusion of normal bone marrow suggests that
      gld is a mutation of the Fas ligand gene.
AB  - lpr and gld mice develop phenotypically indistinguishable systemic autoimmune
      diseases and marked lymphadenopathy dominated by CD4-CD8- T cells. In vivo
      chimera experiments have demonstrated that both lpr T and lpr B cells are
      intrinsically defective. Analogous experiments were conducted using gld mice.
      Lethally irradiated gld mice were given mixtures of congenic gld and normal (+/+)
      bone marrow differentially marked by Ig heavy chain allotype. In sharp contrast
      to lpr-(+)/+ mixed chimeras, gld-(+)/+ chimeras had little autoantibody
      production at 5 months and minimal adenopathy at 6 months, indicating that the
      normal marrow-derived cells corrected the gld defect. Thus, aberrant autoantibody
      production is due to a defect extrinsic to the gld B cell and lymphoproliferation
      is due to a defect extrinsic to the gld T cell. These data support the hypothesis
      that gld mice lack an apoptosis-inducing ligand. The receptor for this ligand may
      be the Fas molecule, which is defective in lpr mice.

PMID- 7505612
TI  - Evidence that intestinal IgA plasma cells in mu, kappa transgenic mice are
      derived from B-1 (Ly-1 B) cells.
AB  - B6-Sp6 transgenic mice carry fully rearranged (BALB/c-derived, Igh-Ca allotype)
      mu heavy chain and kappa light chain transgenes, specific for trinitrophenyl, on
      a C57BL background (Igh-Cb allotype). FACS analyses show that the majority of B
      cells in peripheral lymphoid organs and bone marrow (BM) express transgenic IgM
      exclusively. A small proportion of the B cells, however, express endogenous IgM,
      usually concomitant with transgenic IgM. Three criteria establish that the
      endogenous IgM expressing B cells belong to the B-1 cell lineage. (i) Endogenous
      IgM expressing B cells in B6-Sp6 mice have the same localization pattern as B-1
      cells from normal animals: they are enriched in the peritoneal cavity. (ii) The
      endogenous IgM+ B cells have the phenotype of B-1 cells: the endogenous IgM+
      peritoneal B cells express Mac-1 (CD11b) and low levels of IgD, and most also
      express CD5 (Ly-1). (iii) B6-Sp6 BM poorly reconstitutes endogenous IgM+ B cells,
      just as adult BM from normal mice poorly reconstitutes B-1 cells. In contrast, B
      cells which only express the transgene are readily reconstituted by B6-Sp6 BM.
      The few endogenous IgM+ cells in the B6-Sp6 BM recipients are located in the
      peritoneal cavity and have the phenotype of B-1b cells (previously the Ly-1 B
      sister population), which are known to be reconstituted by adult BM. Two-color
      immunofluorescence staining of tissue sections from the gut and from isolated gut
      lamina propria cells shows the presence of many IgA containing cells, about one
      third of which simultaneously express cytoplasmic (transgenic) IgM. The C-region
      of this IgA is produced by endogenous C alpha genes, because the transgene
      encodes only for C mu. Furthermore, the majority of gut IgA containing cells do
      not express the idiotype of the transgene, indicating that most of the gut IgA
      cells are encoded by endogenous VH genes and thus the result of an isotype switch
      from endogenous IgM expressing B cells. Since the endogenous IgM+ cells are B-1
      cells (both B-1a and B-1b), the data strongly indicate that the intestinal IgA
      plasma cells also belong to the B-1 cell lineage.

PMID- 7505613
TI  - IL-1 beta induces the coexpression of both nitric oxide synthase and
      cyclooxygenase by islets of Langerhans: activation of cyclooxygenase by nitric
      oxide.
AB  - Autoimmune diabetes is characterized by an early infiltration of lymphocytes into
      and around islets, which is followed by selective destruction of the insulin
      secreting beta-cell. Cytokines released during this inflammatory reaction have
      been implicated as effector molecules which mediate beta-cell destruction. In
      vitro treatment of rat islets with the cytokine IL-1 beta results in an
      inhibition of glucose-stimulated insulin secretion that is mediated by the
      overproduction of nitric oxide. IL-1 beta also stimulates the production of the
      cyclooxygenase (COX) product prostaglandin E2 (PGE2). In this study we have
      examined the effects of IL-1 beta on both inducible nitric oxide synthase (iNOS)
      and inducible cyclooxygenase (iCOX) expression, and the direct effects of nitric
      oxide on the activity of COX. Treatment of rat islets with 5 units/mL IL-1 beta
      induces a similar time-dependent production of both nitrite and PGE2. IL-1 beta
      induced nitrite and PGE2 production is attenuated by the NOS inhibitor NG
      monomethyl-L-arginine (NMMA), but NMMA has no inhibitory effect on the expression
      of either iCOX or iNOS as determined by immunoprecipitation. Actinomycin D
      prevents IL-1 beta-induced iCOX and iNOS expression and the production of both
      nitrite and PGE2 by islets, suggesting that mRNA transcription is required for IL
      1 beta-induced expression of both iNOS and iCOX. The effects of exogenous
      arachidonic acid on both constitutive COX (cCOX) and iCOX activity were also
      investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505614
TI  - Transmembrane organization of the Na,K-ATPase determined by epitope addition.
AB  - The Na,K-ATPase is a membrane-associated enzyme that establishes the internal
      Na+/K+ environment of most animal cells. The catalytic (alpha) subunit of the
      Na,K-ATPase contains multiple transmembrane segments, but the number and location
      of these domains has not been clearly established. We have used epitope addition
      to determine the transmembrane topology of the alpha subunit. An immunoreactive
      peptide was inserted into various regions of the cDNA encoding the rat alpha 1
      subunit, and the constructs were expressed in transfected mammalian cells. The
      intra- or extracellular location of the epitope tags was determined by
      immunofluorescence analysis. Our results indicate that the amino and carboxyl
      termini of the alpha subunit are situated intracellularly, and the polypeptide is
      likely to possess eight membrane-spanning segments. The systematic application of
      epitope tagging may be useful for analyzing the topology of membrane proteins of
      unknown structure.

PMID- 7505615
TI  - A mechanism for rotamase catalysis by the FK506 binding protein (FKBP).
AB  - A detailed mechanism for the catalysis of prolyl isomerization by the rotamase
      enzyme FKBP is proposed on the basis of a model constructed from the known
      structure of the FK506/FKBP complex. The model substrate is bound as a type VIa
      proline turn with the ends exposed to permit longer polypeptide chains (e.g.,
      protein loops) to act as substrates. An ab initio potential for the isomerized
      imide bond is combined with a molecular mechanics representation of the rest of
      the system to calculate the reaction path. The resulting activation energy for
      the enzymatic cis-->trans isomerization is equal to about 6 kcal/mol, in good
      agreement with experiment. The lowering of the barrier relative to the solution
      value of 19 kcal/mol is found to arise from a combination of desolvation of the
      imide carbonyl, ground-state destabilization, substrate autocatalysis, and
      preferential transition-state binding. Minimal rearrangements are required in the
      enzyme and the substrate along the reaction path. The enzyme residues that
      participate in catalysis agree with the available mutation data. The type VIa
      turn model corresponds to a sequence-specific structural motif commonly found on
      the surface of proteins. It is likely to have a role in the formation of protein
      complexes with FKBP-like domains that function as foldases or chaperones.

PMID- 7505616
TI  - Calcium and calmodulin in the control of cellular behavior and motility.

PMID- 7505617
TI  - A thermodynamic model for denaturation of granulocyte colony-stimulating factor:
      O-linked sugar chain suppresses not the triggering deprotonation but the
      succeeding denaturation.
AB  - We have previously reported that the O-linked sugar chain of human granulocyte
      colony-stimulating factor (G-CSF) protects it against denaturation (Oh-eda et al.
      (1990), J. Biol. Chem. 265, 11432-11435). Theoretically, the mechanism of
      denaturation can be argued by supposing an ionized intermediate. At first it was
      thought from the pH dependence of the thermostability that denaturation was
      triggered by a deprotonation with a different pK between intact and
      deglycosylated G-CSF. The theoretical model revealed, however, that intact G-CSF
      has almost the same pK of 7.4 for deprotonation as deglycosylated G-CSF has, but
      a 10-fold smaller rate constant for the succeeding denaturation of the ionized
      intermediate. A sugar chain of human G-CSF, by standing close by Cys-17, may
      prevent free radicals from attacking the deprotonated sulfhydryl group.

PMID- 7505618
TI  - The hammerhead RNA domain, a model ribozyme.

PMID- 7505620
TI  - Ro RNP associated Y RNAs are highly conserved among mammals.
AB  - Y RNAs are small cytoplasmic RNAs which are components of the Ro
      ribonucleoprotein complexes in higher eukaryotes. These complexes are frequently
      recognized by antibodies present in autoimmune sera. In this study we analysed
      the occurrence of Y RNAs in various mammalian and human cell lines and
      erythrocytes by means of hybridization with human Y RNA probes. Y RNAs homologous
      to their human counterparts, both in length and in sequence, were detected in all
      mammalian cells analysed. While hY1 and hY3 analogues were found in all cells, Y4
      and Y5 RNA could not be detected in rodent cells. In addition, Y5 RNA was absent
      from bovine cells. Attempts to determine the sequence of rat Y RNAs by genomic
      cloning resulted in the isolation of a presumptive Y1 RNA pseudogene. Analysis of
      the hY RNA content of various human cell lines showed that all four human Y RNAs
      were present in all cell lines examined. However, the relative levels to which
      these RNAs were expressed showed marked differences.

PMID- 7505619
TI  - Sequence and organization of the human vitamin D-binding protein gene.
AB  - The structure and organization of the human vitamin D-binding protein (DBP) gene
      has been determined. The gene is composed of 13 exons and 12 intervening
      sequences. With the help of the polymerase chain reaction (PCR) introns were
      amplified using exon-specific oligonucleotide primers, and were sequenced after
      subcloning; the exon/intron borders were determined. The introns 2, 5, 7, 9 and
      10 were sequenced completely; the introns 1, 3, 4, 6, 8, 11 and 12 were sequenced
      in part. We designed intron-specific primers for the amplification of each exon
      by the PCR-method. This permits the analysis of mutational and function-related
      sites. By comparison with the genes for human albumin and alpha-fetoprotein the
      gene for DBP/GC is confirmed as a member of this multigene family. The location
      of the introns in the coding region of the human DBP-gene is identical with the
      position of the introns in the rat DBP-gene.

PMID- 7505621
TI  - Mechanism of viroid pathogenesis: differential activation of the interferon
      induced, double-stranded RNA-activated, M(r) 68,000 protein kinase by viroid
      strains of varying pathogenicity.
AB  - Purified potato spindle tuber viroid (PSTVd) was added to an in vitro assay
      system containing purified interferon-induced, dsRNA-activated protein kinase
      (P68). Viroid RNA activated (phosphorylated) the enzyme, although with less
      efficiency than did the synthetic, perfectly matched poly I-poly C. In binding
      experiments, RNA transcripts of the intermediate strain of PSTVd were shown to
      specifically bind to a P68-antibody complex. Activation of the enzyme by a strain
      of PSTVd that results in severe symptoms in infected tomato plants was at least
      ten-fold that by the mild strain. Activation by a strain that results in
      intermediate symptoms was quantitatively similar to activation by the severe
      strain. To our knowledge, this is the first demonstration of a differential
      effect of viroid strains inducing different levels of pathology on any
      biochemical or metabolic system investigated. This differential effect suggests
      that activation of a plant enzyme homologous to mammalian P68 protein kinase may
      represent the triggering event in viroid pathogenesis. Differential activation of
      P68 is surprising, because the primary structures of the mild and severe PSTVd
      strains analyzed differ by only a two-nucleotide inversion (UUC-->CUU) in the
      lower portion of the 'pathogenicity' region of the molecules. This change,
      according to thermodynamic calculations, should have only a minor effect on the
      secondary structure of the viroid molecule. Binding assays indicated that PSTVd
      specifically binds to P68.

PMID- 7505622
TI  - Properties of the satellite RNA of nepoviruses.
AB  - Satellite RNA depend for their multiplication on the co-infection of a host cell
      by a helper virus which can itself multiply independently of the satellite. Four
      types of satellite RNA have been distinguished on the basis of the size of the
      RNA and what sort, if any, of protein they encode. One of them, the B-type,
      comprises relatively large RNA which are messenger RNA for non-structural
      proteins. Many of these satellites are typified by having nepoviruses as helper
      viruses. In general, the presence of nepovirus mRNA satellites in a virus culture
      causes little or no modification to the symptoms of infection by the helper virus
      and has little effect on its yield. Some satellites appear to be highly specific
      to a strain of helper virus but others can be helped by heterologous viruses. The
      proteins encoded by nepovirus mRNA satellites have a M(r) of 38,000 to 48,000 and
      are relatively basic, in particular in the N-terminal and C-terminal parts of the
      molecules. However, there is little similarity in amino acid sequence between
      proteins encoded by different satellites and no peptide motif could be found in
      all satellite proteins. The results of reverse genetics experiments with
      satellites suggest that the satellite-encoded protein is essential for the
      multiplication of the satellite RNA. This system has considerable potential for
      the study of the mechanisms of replication both of satellite and helper virus
      RNA.

PMID- 7505623
TI  - Location of the replication determinants of the satellite RNA associated with
      grapevine fanleaf nepovirus (strain F13).
AB  - A large satellite RNA of 1114 nucleotides, named RNA3, is always found associated
      with the genomic RNAs of grapevine fanleaf virus, isolate F13 (GFLV-F13). RNA3
      encodes a non-structural protein (P3) of M(r) 37K to which no function has
      previously been assigned. Full-length cDNA clones of RNA3 were mutated in the 5'
      and 3' non-coding regions and in the 37K open reading frame. The ability of
      transcripts obtained from these clones to be replicated was investigated by
      protoplast infection in the presence of a helper virus. We demonstrate that the
      5' and 3' non-coding regions as well as the satellite-encoded P3 protein are
      essential for replication of the GFLV-F13 satellite RNA. Our results suggest that
      two hydrophobic regions located at the N- and C-extremity of P3 and a zinc-finger
      motif near the C-terminal extremity of P3 are probably involved in the
      replication of this satellite. Analysis of the in vitro translation products from
      transcripts of RNA3 clones of different lengths indicates that the double band
      formed by P3 could result from phosphorylation of a part of this protein.

PMID- 7505624
TI  - [Comparison of proteins, connected with 7SL RNA from dog pancreas and rabbit
      reticulocytes].
AB  - The 7SL RNA has been shown to exist in canine pancreatic cells as specific
      complexes with proteins and to form RNP-particles dispersed heterogeneously in
      the range between 12S and 14S. One of the major protein components of those RNPs
      is a protein of a molecular mass of 85 kDa whose electrophoretic motility is the
      same as that of the protein detected earlier in SRP-like particles from rabbit
      reticulocytes. It is assumed that canine pancreatic cells contain SRP-like
      particles analogous to those discovered in rabbit reticulocytes. Among other
      proteins, the major ones are evidently high molecular weight SRP subparticles (M
      = 72, 69 and 54 kDa) differing in electrophoretic motility from SRP-like
      particles. The proteins detected in the sedimentation region of canine pancreatic
      SRP have acidic properties and during two-dimensional electrophoresis are
      distributed at pH varying from 5.5 to 6.5. The protein of SRP-particles is
      suggested to have neutral properties (pI-7).

PMID- 7505625
TI  - Rapid identification of T helper and T cytotoxic/suppressor lymphocytes with an
      oxazine dye.
AB  - Peripheral blood lymphocytes displayed a plurality of sizes and colors when
      exposed first to a methanolic solution of C.I. basic blue 141, then to an aqueous
      alkaline solution of the same dye and rinsed in a neutral HEPES buffer containing
      trace amounts of various salts. As confirmed with purified lymphocyte
      subpopulations obtained with a cell sorter, T helper cells (CD4) were small and
      their nuclei and cytoplasm stained deep blue. T cytotoxic/suppressor cells (CD 8)
      were larger than T helper cells, their nuclei stained pale green or blue green
      and their cytoplasm contained a cluster of magenta colored granules. From start
      to finish, the stain takes 15 min to perform. Used in the manner described, basic
      blue 141 holds promise as a rapid means of identifying and differentiating CD4
      and CD8 cells under the ordinary light microscope without using monoclonal
      antibodies or fluorescence.

PMID- 7505626
TI  - Improved Randolph stain for direct leukocyte differentiation and determination of
      total eosinophil count in a hemocytometer.
AB  - Identification and quantification of eosinophilic granulocytes are commonly
      performed indirectly by total leukocyte count and white cell differentiation in
      smears or cytocentrifuge preparations. Using a combination of four dyes,
      phloxine, Biebrich scarlet, methylene blue, and crystal violet, at 50-800
      micrograms/ml, we have substantially improved an earlier method for
      differentiating leukocytes in a hemocytometer. This direct method allowed a rapid
      and reliable enumeration of eosinophils and their differentiation from
      neutrophils, lymphocytes and monocytes in peripheral blood and leukocyte
      fractions. The results obtained using this stain correlated with the leukocyte
      counts calculated from May-Grunwald-Giemsa stained smears in 100 patients with
      eosinophilia of various etiologies (r = 0.95; p < 0.01). This simple method is a
      useful improvement for eosinophil enumeration in field studies and biological
      experiments where the purity of cell suspensions must be evaluated without delay.
      The method cannot be substituted for the commonly used indirect technique which
      also allows the identification of other leukocyte lineages and their precursors.

PMID- 7505627
TI  - Some properties of new DNA-specific bisbenzimidazole fluorochromes without a
      piperazine ring.
AB  - Three new bisbenzimidazole (BBI) compounds, which differ from Hoechst 33258
      mainly by substitution of a N-dimethylaminopropylcarboxamide group in place of
      the N-methylpiperazine ring, were studied for their DNA- and AT-base pair
      specificity as well as for their ability to be quenched by incorporated 5
      bromodeoxyuridine (BrdU). Each of them had DNA binding specificity comparable to
      or greater than that of Hoechst 33258 and each had a greater specificity for AT
      rich regions than did Hoechst 33258. The dependence of fluorescence of new dyes
      on the BrdU-incorporation into DNA is different from that of Hoechst 33258 and
      related compounds with piperazine ring. The quenching effect is much weaker, and
      two of the new compounds (BBI-1 and BBI-2) even show somewhat enhanced binding
      (fluorescence) at lower concentrations. Certain BBI dyes without piperazine ring
      may have some advantage over Hoechst for accurate DNA (AT-specific) measurements.
      The piperazine ring appears to play an important role in the yet unknown
      mechanism of Hoechst quenching by incorporated BrdU.

PMID- 7505628
TI  - Differentiation of tyrosine hydroxylase and phenol oxidase after electrophoresis.
AB  - Tyrosine hydroxylase and phenoloxidase differ in that tyrosine hydroxylase
      (E.C.1.14.16.2) can hydroxylate tyrosine into -o-diphenol, but cannot oxidize the
      -o-diphenol, whereas phenoloxidase (E.C.1.14.18.1) is capable of oxidizing -o
      diphenol to quinone. This difference can be exploited by staining tyrosine
      hydroxylase activity with a substrate-PMS-NBT method and staining the
      phenoloxidase with a dopamine-MBTH method. Based on the staining properties of
      the bands separated after electrophoresis, tyrosine hydroxylase has been
      differentiated from phenoloxidase in the silkworm Bombyx mori and the occurrence
      of tyrosine hydroxylase has been reported for the first time in this worm.

PMID- 7505630
TI  - Biological evaluation of an ionomeric bone cement by osteoblast cell culture
      methods.
AB  - Periosteal derived bovine osteoblast-like cells migrated in culture onto an
      ionomeric cement. Cell cultures were maintained for 4 weeks and used to study the
      in vitro behaviour of cells on the ionomeric bone cement (IC). The cells produced
      bone matrix proteins (osteocalcin, bone sialoprotein II) and were osteoblast
      like. The osteoblast-like cells colonized the substrate in monolayers and
      produced an extracellular matrix as seen by light and scanning electron
      microscopy. Morphological comparison between cells growing on the ionomeric bone
      cement and cortical bone revealed no significant difference in phenotypic
      expression. Staining for aluminium in osteoblasts growing on the IC showed an
      uptake and storage of aluminium in the cells. Energy dispersive X-ray
      microanalysis revealed high concentrations of aluminium and silicon in the
      periosteal tissue. Despite the known toxic effect of aluminium in vivo and in
      vitro on osteoblasts, no signs of toxicity were apparent on light and scanning
      electron microscopy analysis.

PMID- 7505629
TI  - Immunohistochemical detection of sialyl Le(x) antigen on mucosal Langerhans cells
      of human oral mucosa following neuraminidase pretreatment.
AB  - Histochemical assessment of selected carbohydrate sequences on Langerhans cells
      of human oral mucosa was made by combined use of enzyme digestion and
      immunostaining with monoclonal antibodies against specific carbohydrate
      structures. In both frozen sections and epithelial sheets without the enzyme
      pretreatment, mucosal Langerhans cells, identified by positive staining with anti
      CD1a and HLA-DR antibodies, did not express any carbohydrate antigens on their
      surface. In contrast, following neuraminidase pretreatment of both types of
      material, the fucosylated type 2 chain (Le(x)) became detectable on Langerhans
      cells, indicating that sialic acid is the terminal residue of this sequence.
      Other enzymes were ineffective in this apparent unmasking, and the staining
      patterns of the other related carbohydrate sequences (Le(y)+, Le(a), Le(b))
      remained unaffected by pretreatment with any of the enzymes used. These findings
      suggest that the mucosal Langerhans cells possess a unique carbohydrate chain,
      the sialyl fucosylated type 2 sequence (sialyl Le(x) antigen).

PMID- 7505631
TI  - Identification of anti-idiotypic antibodies to anti-phosphotyrosine antibodies in
      human sera.
AB  - We have recently identified in SLE sera antibodies against phosphotyrosine. They
      were also detected in normal sera and gammaglobulin preparations, suggesting that
      they belong to natural autoantibodies. In this paper, the occurrence of anti
      idiotypic antibodies against anti-phosphotyrosine antibodies, in the above
      mentioned samples, is investigated. In order to identify these anti-idiotypic
      antibodies ELISA, immunoprecipitation and immunoblotting are performed. Our data
      demonstrate the presence of anti-idiotypic antibodies specific to anti
      phosphotyrosine antibodies in SLE sera as well as in normal sera, suggesting that
      these anti-idiotypic antibodies are also auto-anti-idiotypic antibodies. The
      densitometry of immunoblots reveals significantly higher levels of anti-idiotypic
      antibodies in SLE sera. Based on the competition inhibition studies we conclude
      that some of these anti-idiotypic antibodies belong to beta/gamma type.

PMID- 7505632
TI  - ICAM-1 and E-selectin expression in lesional biopsies of psoriasis patients
      responding to systemic FK 506 therapy.
AB  - FK 506 is a new immunosuppressive agent with a similar molecular action to
      cyclosporin A. We have investigated immunohistochemical changes in lesional
      biopsies of seven patients with severe recalcitrant chronic plaque psoriasis
      receiving systemic FK 506 therapy. Within 4 weeks of start of treatment, there
      was a striking reduction in psoriasis area and severity index (mean reduction
      87.4%), accompanied by marked reductions in dermal and epidermal CD4+ and CD8+
      cells. Investigation of biopsies obtained 4-8 weeks after start of treatment
      revealed a significant fall in the numbers of activated mononuclear cells
      expressing CD25 (IL-2 receptor alpha-chain), HLA-DR, or CD11a (lymphocyte
      function-associated antigen-1, LFA-1 alpha chain). In contrast, the number of
      epidermal CD1+ (Langerhans) cells increased in response to FK 506 therapy. Study
      of leukocyte adhesion-related epitopes in active disease revealed strong
      expression of CD54 (intercellular adhesion molecule-1, ICAM-1) and E-selectin
      (previously known as endothelial leukocyte adhesion molecule-1) both on
      microvascular endothelial cells and of ICAM-1 on infiltrating mononuclear cells;
      ICAM-1 was also expressed weakly on epidermal keratinocytes. Vascular cell
      adhesion molecule-1 (VCAM-1) was either absent or expressed rarely on vascular
      endothelium. In response to FK 506 treatment, both ICAM-1 and E-selectin
      expression on blood vessels was reduced consistently but nevertheless persisted,
      even in individuals exhibiting total clearance of psoriatic lesions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7505633
TI  - Immunochemical analysis of an arginine-rich systemic lupus erythematosus
      autoepitope.
AB  - The MRL mouse strain spontaneously produces antinuclear autoantibodies that
      recognize DNA and the small nuclear ribonucleoprotein (snRNP) antigens. The
      monoclonal antibody 2.73 was derived from the lupus prone MRL/n line and is
      reactive with the 70K protein of the U1 snRNP particle. The epitope recognized by
      2.73 was characterized by peptide and inhibition ELISA analysis. Several
      arginine/aspartic acid (RD) repeats of varying lengths are found in the carboxyl
      terminus of the 70K protein and are responsible for immunoreactivity with 2.73.
      We investigated the contribution of charge and found that the immunoreactivity of
      2.73 and the 70K protein is specific for the RD repeats. The presentation of the
      epitope may also contribute to the epitopes immunoreactivity with the 2.73 mouse
      monoclonal autoantibody.

PMID- 7505634
TI  - Depolarization of Raman scattering from some nucleotides of RNA and DNA.
AB  - Depolarization ratios of Raman bands, excited at 488.0 nm, of guanosine-5'
      monophosphoric acid, cytidine-5'-monophosphoric acid, adenosine-5'-monophosphoric
      acid, thymidine-5'-monophosphoric acid, and uridine-5'-monophosphoric acid have
      been measured in their H2O and D2O solutions in the spectral region from 300 to
      1800 cm-1. For comparison, the disodium salt of 2'-deoxyadenosine-5'
      monophosphoric acid was also subjected to the depolarization measurement in its
      H2O solution. The results have been correlated with possible orientations of the
      principal axes of the Raman scattering tensors as well as with the relative
      magnitudes of the tensor components. Results should be useful for future
      polarized Raman studies of synthetic and natural DNA.

PMID- 7505635
TI  - Low oxygen affinity derivatives of human hemoglobin by fixation of polycarboxylic
      dextran to the oxyform.
AB  - Solutions of modified adult human hemoglobin (Hb) have potential applications as
      physiological oxygen carriers. The chemical modification that has been the most
      studied during the last few years is the cross-linking of the protein between its
      two alpha beta dimers, in order, first, to hamper their diffusion through the
      kidney and therefore increase the plasma persistence of Hb, and second, to
      decrease its oxygen affinity. However, despite the cross-linking, the vascular
      retention time is only increased by a factor of three, and a supplementary
      modification of cross-linked Hb is needed in order to further improve its in vivo
      half-life. The Hb derivatives described in this paper were obtained by the
      covalent fixation of benzene tetracarboxylate-substituted dextran onto oxyHb. The
      resulting conjugates all exhibited a higher P50 than native Hb. The experiments
      carried out in the presence of inositol hexaphosphate showed that the allosteric
      sites of Hb molecules were occupied by the polymeric reagent. The important
      decrease in the Bohr effect and the lack of the Cl- effect on the oxygen-binding
      properties proved that the Val 1 alpha residue was also substituted. Finally, the
      ability of some conjugates to unload as much O2 as blood, together with their
      other properties, make them quite promising candidates as red cell substitutes.

PMID- 7505636
TI  - Solution conformation study of substance P methyl ester and [Nle10]-neurokinin A
      (4-10) by NMR spectroscopy.
AB  - High-resolution proton spectra at 500 MHz of two tachykinin peptides, substance P
      methyl ester (SPOMe) and [Nle10]-neurokinin A (4-10), have been obtained in
      dimethylsulfoxide (DMSO), and for SPOMe, also in 2,2,2-trifluoroethanol
      (TFE)/water mixtures. Complete chemical shift assignments for these peptides were
      made based on two-dimensional (2D) nmr techniques, correlated spectroscopy and
      total COSY. J coupling measurement and nuclear Overhauser effect spectroscopy
      (NOESY) were then used to determine the conformation of these peptides in the
      various solvents. Based on the J coupling, NOE correlations, and temperature
      coefficients of the NH resonances, it is concluded that these two peptides exist
      in DMSO at room temperature as a mixture of conformers that are primarily
      extended. For SPOMe in TFE/water with high TFE content, however, helical
      structures are found to be present, and they become quite clear at temperatures
      between 270 and 280 K. The variation of the 13C chemical shifts of the C alpha
      (the secondary shift) with TFE contents corroborates this conclusion. The NOE and
      C alpha shifts show that the main helical region for SPOMe lies between 4P and
      9G. The C-terminus segment L-M-NH2 is found to be quite flexible, which appears
      to be quite common for neurokinin-1 selective peptides.

PMID- 7505637
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the density of
      stem cell factor receptors (c-kit oncogene product) on a GM-CSF-dependent human
      myeloid cell line.
AB  - By employing a monoclonal antibody against the stem cell factor receptor (SCF-R),
      c-kit oncogene product, we analysed in flow cytometric technique the density of
      SCF-R on GM/SO cells which were incubated under various culture conditions. These
      experiments revealed that there is an inverse correlation between the SCF-R
      density on the cells and the doses of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) in culture medium; the lower the dose, the higher the density of
      SCF-R on the cells. More detailed analyses showed that, in contrast to SCF which
      rapidly downregulates its own receptor, GM-CSF does not alter the measurable
      level of SCF-R in an exposition period of 60 minutes, which suggests that the
      internalization or shedding of the receptor is not the mechanism of action. Since
      the most striking difference regarding density of SCF-R between GM-CSF-treated
      and untreated cells was observed on day 2, the modulation of c-kit oncogene
      protein by GM-CSF likely occur prior to expression of protein onto the cell
      surface. In order to exclude the possibility that altered cell viability due to
      insufficient GM-CSF content in culture medium might be responsible for the
      increased SCF-R densities on GM-CSF-dependent cells, we subsequently generated a
      GM-CSF-independent subclone which still responded to GM-CSF as well as the
      dependent did. The experiments carried out with this subclone confirmed the
      results presented above. Thus our data suggest that GM-CSF is directly involved
      in the regulation of SCF receptor density on GM/SO cells.

PMID- 7505638
TI  - Introgression between members of the Simulium damnosum complex: larvicidal
      implications.

PMID- 7505639
TI  - Removal of trypsin complexed alpha-2 macroglobulin by plasma fractionation.
AB  - The aim of this study is to assess in vitro the efficacy of a plasma fractionator
      to remove trypsin complexed alpha 2MG (alpha-2 macroglobulin) from human plasma
      in a manner analogous to the reticuloendothelial system (RES). Eval filter type
      "4A" (Kuraray Co., Osaka, Japan) was chosen as a plasma fractionator. Two and one
      half liters of bovine trypsin spiked human plasma was perfused in vitro through
      the fractionator in a single pass mode (n = 5). The concentrations of complexed
      alpha 2MG, total alpha 2MG, albumin, and IgM were measured before and after
      fractionation, and the concentration of free alpha 2MG and the sieving
      coefficients of each solute were calculated. The concentration of the trypsin
      complexed alpha 2MG measured by ELISA was significantly decreased by
      fractionation with Eval "4A" from 103.7 +/- 16.7 to 13.8 +/- 8.2 mg/L (reduction
      of 86.7%). Mean sieving coefficients of each solute were 0.133 +/- 0.079 in
      complexed alpha 2MG, 0.203 +/- 0.065 in free alpha 2MG, 0.203 +/- 0.065 in total
      alpha 2MG, 0.770 +/- 0.130 in albumin, and 0.070 +/- 0.010 in IgM. Although in
      vivo study will be required in patients with acute pancreatitis, in vitro study
      shows the feasibility of membrane plasma fractionation in eliminating trypsin
      complexed alpha 2MG.

PMID- 7505640
TI  - Effect of blood-membrane interactions on solute clearance during hemodialysis.
AB  - Clearances obtained during clinical hemodialysis are smaller than those predicted
      from in vitro measurements obtained with cell and protein free solutions,
      although the exact cause of this clearance reduction is unclear. This study
      examined the specific effects of blood contact on the in vitro clearance of urea,
      vitamin B12, and polydispersed dextrans using cuprophan, AN69, and polysulfone
      dialyzers. Blood contact caused a significant reduction in solute clearance, with
      the actual reduction a complex function of dialyzer type, solute, and
      ultrafiltration rate. The reduction in urea clearance at zero ultrafiltration
      ranged from 9% (polysulfone dialyzer) to 19% (cuprophan dialyzer). The percent
      reduction in clearance increased with increasing solute molecular weight for AN69
      and polysulfone dialyzers, with the clearance after blood contact essentially
      zero for the larger dextrans (molecular weight > 15,000). The relative
      contributions of fiber blockage and membrane transport were examined using a
      theoretical model for solute transport during dialysis, with the membrane
      properties evaluated from independent experiments. The in vitro clearance data
      obtained in this study were in agreement with clinical observations, suggesting
      that differences between in vivo and in vitro clearances are largely the result
      of blood-membrane interactions (i.e., fiber blockage and reduced membrane
      transport properties).

PMID- 7505641
TI  - Choroidal rupture.
AB  - Choroidal rupture resulting from ocular trauma is classified as direct or
      indirect, depending on the location of the lesion. Direct ruptures occur at the
      site of impact and are usually located anteriorly and parallel to the ora
      serrata; the more common indirect ruptures occur in the posterior pole and are
      usually concentric to the optic nerve. There are two theories proposed to explain
      the pathogenesis of injury. The most significant sequela of choroidal rupture is
      formation of a choroidal neovascular membrane (CNVM). Patients with good acuity
      and rupture in close proximity to the macula should be monitored; fluorescein
      angiography may be used as an aid to diagnosis. Early-onset CNVM occurs within 6
      months after injury, whereas the late-onset form of CNVM may require many years
      to pass before becoming clinically evident. Laser photocoagulation is used to
      arrest the growth of the neovascular membrane in both types of presentations.

PMID- 7505642
TI  - Nonselective cation channels. Pharmacology, physiology and biophysics.

PMID- 7505643
TI  - Mechanosensitive nonselective cation channels in the antiluminal membrane of
      cerebral capillaries (blood-brain barrier).
AB  - Single stretch-activated (SA) cation channels have been investigated in the
      antiluminal membrane of freshly isolated brain capillaries. SA-channels did not
      distinguish between K+ and Na+ ions and were also permeable to Ca2+ and Ba2+
      ions. With monovalent cations in the patch pipette the single-channel conductance
      was 37 pS and with the divalent cations Ba2+ and Ca2+ slope conductance was 16
      and 19 pS, respectively. The open probability of the SA-channel increased with
      increasing negative pressure as well as with depolarization. Cell swelling
      induced by hypotonic shock activated the SA-channels in cell-attached
      experiments. The contribution of SA-channels to the regulation of cerebrospinal
      fluid in brain edema is discussed.

PMID- 7505644
TI  - The gap junction channel.

PMID- 7505645
TI  - Cyclic nucleotide-gated nonselective cation channels: a multifunctional gene
      family.

PMID- 7505646
TI  - Cyclic AMP-gated cation channels of olfactory receptor neurons.
AB  - Odor-induced electrical activity in vertebrate olfactory receptor neurons is, at
      least in part, the result of the direct cyclic AMP-dependent activation of a
      nonselective cation channel. Single-channel recordings from extraciliary regions
      of isolated salamander olfactory receptor neurons have greatly improved our
      knowledge about distinctive properties of the cAMP-gated channel such as channel
      kinetics, modulation through divalent cations, and pharmacology. Because of the
      central role of these channels in the transduction cascade, these efforts have
      led to a better understanding of the physiology of olfactory transduction.

PMID- 7505647
TI  - Renal epithelial cells show nonselective cation channel activity and express a
      gene related to the cGMP-gated photoreceptor channel.
AB  - Nonselective cation channels have been found in various parts of the nephron and
      represent a heterogeneous group of channels. We briefly review their putative
      physiological function. Renal epithelial nonselective cation channels may play a
      role in volume regulation, calcium entry, cell proliferation, and sodium
      reabsorption. In some renal epithelia cGMP seems to be involved in the regulation
      of nonselective cation channels. Furthermore, there is evidence that a gene
      related to the cGMP-gated photoreceptor channel, a well-characterized,
      nonselective cation channel, is also expressed in whole rat kidney tissue. In the
      context of these observations, we review recent findings from our own work on a
      nonselective cation channel in the M-1 mouse cortical collecting duct cell line.
      We could demonstrate that M-1 cells show nonselective cation channel activity in
      inside-out patches and express a gene related to the cGMP-gated photoreceptor
      channel (Proc. Natl. Acad. Sci. USA 89:10262-10266, 1992). The possibility of a
      relation between the kidney channel and the photoreceptor channel is discussed.

PMID- 7505648
TI  - Ciliary cation conductances in olfactory receptor cells of the clawed toad
      Xenopus laevis.
AB  - One transduction pathway in olfactory receptor neurons is a cascade of receptors,
      a G-protein, adenylate cyclase, cAMP, and a cyclic nucleotide-activated cation
      conductance. Here, we show that this conductance is also present in olfactory
      cells of Xenopus laevis. With optical recordings from the cell's dendritic knob,
      we show that this conductance, when activated by odors, leads to an increase of
      intracellular calcium. It is further shown that there is a second cation
      conductance on the cilia of these cells which is modulated by calcium and can be
      activated by the application of odorants.

PMID- 7505649
TI  - Control of cell function by neuronal calcium-activated nonselective (CAN) cation
      channels.

PMID- 7505650
TI  - Nonselective cation channels in exocrine gland cells.
AB  - The nonselective cation channel has been described in a wide variety of
      nonexcitable cells. However even in such closely related tissues as the
      pancreatic acinar cell and the lacrimal acinar cell, which both possess a
      superficially similar channel, recent work has shown fundamental differences in
      channel regulation (Sasaki and Gallacher, 1992; Thorn and Petersen, 1992). These
      differences are a reflection of a diverse function of the nonselective channel in
      different tissues.

PMID- 7505651
TI  - Nonselective cation channels in brown and white fat cells.

PMID- 7505652
TI  - Inhibitors of nonselective cation channels in cells of the blood-brain barrier.
AB  - In the antiluminal membrane of isolated capillaries of rat and porcine brain
      (blood-brain barrier) nonselective cation channels with g = 31 pS were observed
      in cell-excised membrane patches. The channel inactivated by decreasing cytosolic
      Ca2+ below 1 microM and was inhibited by 1 mM ATP on the intracellular side.
      Anions and divalent cations did not pass the channel, but Na+ and K+ were equally
      permeant. Like the nonselective cation channel of rat exocrine pancreatic cells,
      the channel in cerebral capillary endothelial cells was inhibited reversibly by
      derivatives of diphenylamine-2-carboxylate (DPC), like 3',5-dichlorodiphenylamine
      2-carboxylic acid (DCDPC, ki = 1 microM), and flufenamic acid (ki = 4.9 microM).
      4'-methyldiphenylamine-2-carboxylic acid (4-MDPC), 5-chloro-2(3
      trifluormethylphenylamino)-3-nitrobenzoic acid, and 5-nitro-2-(3
      phenylpropylamino)-2-carboxylic acid (NPPB), as well as the antiinflammatory drug
      ((Z)-5-chloro2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-ox o-1H-indole-1-
      carboxamide (Tenidap)) had a relatively low blocking potency (ki > 10 microM).
      Gadolinium (10 microM), a blocker of stretch-activated channels, inhibited the
      nonselective cation channel potently.

PMID- 7505653
TI  - Nonselective cation channels in cells of the crypt-base of rat distal colon.
AB  - Cells in the base of isolated intact crypts of rat distal colon were investigated
      with the slow whole-cell patch-clamp technique with nystatin in the patch
      pipette. Addition of either prostaglandin E2 or forskolin to the bath depolarized
      the cell from -74 mV to -27 mV. This depolarization was reversed when bath Na+
      was replaced by N-methyl-D-glucamine (NMDG+), or when flufenamic acid (50 microM)
      was added to the bath. In cell-attached and cell-excised patches of the
      basolateral membrane nonselective cation channels (gamma = 38 pS, 35 degrees C)
      were recorded. It is concluded that nonselective cation channels are activated by
      PGE2 and forskolin. The channels could be involved in cell proliferation.

PMID- 7505654
TI  - Poorly selective cation channels in apical membranes of epithelia.
AB  - The apical membrane of frog skin contains two types of pathways which allow the
      passage of several monovalent cations in the absence of external Ca2+.
      Differences between the two pathways concern their open-close kinetics,
      selectivity, and the affinity for several blocking agents. Type S channels open
      and close relatively slowly, whereas type F channels display fast open-close
      kinetics. Both channel types allow the passage of Na+, K+, and Rb+ currents which
      are blocked by divalent cations and La3+ added to the extracellular side. Type F
      channels are permeable for Cs+ which is, however, excluded from type S channels.
      Shifts in open-close kinetics induced by Mg2+ occur at concentrations below 5
      microM for type F channels, whereas more than a tenfold higher dose is required
      for the type S pathway. UO2(2+) concentrations up to 100 microM only occlude type
      S channels while 100 microM tetracaine selectively blocks type F channels. Apical
      membranes of toad urinary bladder, cultured amphibian renal epithelia (A6), and
      toad colon contain only type F channels. In toad bladder and A6 cells volume
      expansion strongly activates this pathway. Macroscopic currents carried by Ba2+
      and Ca2+ could be recorded after activation of toad bladders with oxytocin and
      treatment of the apical surface with nanomolar concentrations of Ag+, which seems
      to interact with a site located at the channel interior.

PMID- 7505655
TI  - Nonselective cation channels in cardiac and smooth muscle cells.
AB  - In cardiac and smooth muscle cells, nonselective cation channels can be activated
      by hormones and neurotransmitters, by cell stretch, and by changes in membrane
      potential. Activation of nonselective cation channels can depolarize the cell
      membrane, induce Ca2+ influx through voltage-gated Ca2+ channels and contraction.
      Activation of nonselective cation channels may trigger contraction even when
      membrane depolarization is absent or when voltage-gated Ca2+ channels are
      blocked, provided the Ca2+ permeability of these channels is sufficiently high.

PMID- 7505656
TI  - Physiology of muscarinic receptor-operated nonselective cation channels in guinea
      pig ileal smooth muscle.
AB  - Stimulations of autonomic nerves in smooth muscle often evoke both fast and slow
      excitatory junction potentials (EJPs), which are thought to involve activations
      of several distinct types of nonselective cation channels (NSC channels). The ACh
      activated NSC channel in guinea-pig ileum (I(ns), ACh) is one probably
      responsible for the slow EJP and seems to undergo various regulations. This short
      paper will review the physiology of I(ns),ACh, with particular emphasis on its
      dynamic interactions with other physiologically important factors such as the
      membrane potential, [Ca2+]i and pH.

PMID- 7505657
TI  - Nonselective ion pathways in human endothelial cells.
AB  - Four probably different transmembrane pathways are described in human endothelial
      (EN) cells that are all nonselective for cations. i) A nonselective cation
      channel that is more permeable for Na+ and K+ than for Ca2+ can be gated by
      agonists such as histamine. This channel provides an agonist-gated entry route
      for Ca2+ into EN cells with a single-channel conductance of 25 pS for Na+, K+,
      and approximately 4 pS for Ca2+ (110 mM). ii) Another Ca(2+)-permeable pathway
      can be activated by shear stress. This supposedly mechanically activated channel
      is more permeable for divalent than for monovalent cations and provides mechano
      sensing properties to EN cells. iii) A third ionic current, activated by the
      selective Ca(2+)-ATPase blocker thapsigargin, seems to be related to Ca(2+)
      release from Ca(2+)-stores in the endoplasmic reticulum. In EN cells, this Ca(2+)
      entry route is cation selective, but cannot differentiate between Na+ and K+.
      Activation of this nonselective current is associated with an increase in
      intracellular Ca2+. We therefore assume a Ca(2+)-entry through this thapsigargin
      activated pathway. iv) A nickel-blockable, Ca(2+)-permeable, nonselective leak is
      described that is present in nonstimulated EN cells. It will be discussed whether
      agonist-gated channels and leak channels might be related to the Ca(2+)-release
      activated Ca(2+)-entry mechanism.

PMID- 7505658
TI  - Nonselective cation channels: physiological and pharmacological modulations of
      channel activity.
AB  - Cation channels play a major role in fast and sustained cellular responses to
      hormones and neurotransmitters. They contribute to depolarization of the membrane
      and--in most cases--to an increase in the intracellular Ca2+ concentration.
      Nonselective cation channels presumably form a large family of diverse channels
      which are modulated by various extracellular and intracellular signals. Structure
      and regulation of ligand-operated and cyclic nucleotide-activated nonselective
      cation channels found in synapses and sensory receptor cells, respectively, are
      well documented; none of the structures of other cation channels are known.
      Except for ligand-operated and stretch-activated channels, G-proteins form the
      link between the involved receptors and signalling cascades stimulating
      nonselective cation channels. Observed in numerous cellular systems is hormonal
      activation of cation channels by hormones or neurotransmitters interacting with
      heptahelical receptors inducing a phosphoinositide breakdown (PI response);
      several pathways stimulated within the PI response may generate signals involved
      in cation channel activation. Pharmacological modifications of nonselective
      cation channels by inorganic and organic blockers are so far extremely limited;
      various blockers have been described but unfortunately lack high specificity for
      these channels.

PMID- 7505659
TI  - The role of a PDGF-activated nonselective cation channel in the proliferative
      response.
AB  - Murine fibroblasts have a 28 pS calcium- and voltage-insensitive NSC that becomes
      quiescent at G0 arrest and is rapidly and specifically activated by PDGF.
      Activation is produced by the discrete loss of long channel closures. The NSC can
      be rapidly and reversibly blocked with the NSAID flufenamic acid, through a
      prostaglandin-independent mechanism. The cell cycle (not viability) is blocked
      concomitantly with NSC block. A somatic cell mutant with altered NSC conductance
      has been isolated and used to clone the genomic locus of the channel. The mutant
      growth phenotype adds further support to the participation of NSC conductance in
      cell cycle control.

PMID- 7505660
TI  - Cation channels in oocytes and early states of development: a novel type of
      nonselective cation channel activated by adrenaline in a clonal mesoderm-like
      cell line (MES-1).
AB  - The expression of receptors and ion channels alters during growth, maturation,
      and after fertilization of oocytes reflecting functional changes. Besides voltage
      dependent ion channels, oocyte membranes possess an IP3-activated cation channel
      mediating a prolonged Ca2+ influx. The Ca2+ is thought to be involved in
      maturation and fertilization. Alternatively, mono- and divalent cations can enter
      oocytes via stretch-activated channels. The oocyte channel population is further
      modified during subsequent embryogenesis, suggesting that ionic channels
      obviously become expressed at specific states of embryological differentiation
      and in tissue-specific manner. The resulting differences in functional ion
      channel populations of adult cells underlie the large diversity of cells and
      their function. Conversely, differentiation and cell proliferation themselves
      depend on ion transport. Ca2+ ions have been shown to play a pivotal role in
      these processes. Nonselective cation channels represent one possible pathway for
      Ca2+ entry into the cell and, therefore, might be involved in the regulation of
      embryological development. Undifferentiated embryonal carcinoma cells (P19),
      visceral endoderm-like cells (END-2), epithelioid ectoderm-like cells (EPI-7),
      mesoderm-like cells (MES-1), and parietal yolk sac cells (PYS-2) have been used
      as a model to study the expression of ionic channels during early development. In
      MES-1 cells a nonselective cation current was activated by adrenaline.
      Interestingly, the intracellular pathway for activation of these channels
      involved the cascade of activation of the cAMP-dependent protein kinase (PKA)
      resulting in protein phosphorylation. This mechanism is well known for Ca2+
      channel stimulation in cardiac and skeletal muscle both originating from the
      mesoderm.

PMID- 7505661
TI  - Nonselective cation channels.

PMID- 7505662
TI  - Slowly-activating cation channels in the vacuolar membrane of plants.
AB  - Among other ion channels and transport proteins, the membrane of plant vacuoles
      contains a voltage- and calcium-dependent cation channel with activation kinetics
      in the range of seconds. This SV(= slow vacuolar)-channel has a unit conductance
      of 60 to 80 pS (in symmetrical 100 mM cation solution) and is strictly inward
      rectifying. Investigations on the pharmacology of this protein revealed
      reasonable similarities to calcium-dependent potassium channels of large
      conductance.

PMID- 7505663
TI  - Structure, diversity, and ionic permeability of neuronal and muscle acetylcholine
      receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) form a family of ligand-gated, cation
      selective channels that are concentrated at cholinergic synapses on vertebrate
      neurons and muscle cells. At the neuromuscular endplate, muscle nAChRs bind
      acetylcholine released by the presynaptic motor neuron. The receptors then
      undergo a conformational change that opens their ion channels. Cations move
      passively through the water-filled pores down their electrochemical gradients,
      completing synaptic transmission by depolarizing the postsynaptic muscle. The
      channel only weakly discriminates among permeant cations, which include all
      monovalent and divalent cations that are small enough to fit through the
      narrowest cross section. The membrane-spanning region of the pore is lined by
      uncharged domains that are bracketed by residues with net negative charge. The
      pore has large entrance vestibules, especially facing extracellularly. The
      narrowest cross-section is located near the cytoplasmic end of the membrane
      spanning region, and this short narrow region probably provides the main cation
      binding site that is directly in the permeation pathway. Neuronal nAChRs share
      many of the properties of muscle nAChRs, but the neuronal receptor subtypes are
      more heterogenous genetically, pharmacologically, and functionally. There are
      especially important functional differences between muscle and neuronal nAChRs.
      For example, neuronal nAChRs are more highly permeable to Ca2+ and physiological
      levels of Ca2+ very potently modulate neuronal nicotinic currents. This variety
      of nAChRs suggests that these receptor/channels serve many roles in the excitable
      tissues of vertebrates.

PMID- 7505664
TI  - AMPA-type glutamate receptors--nonselective cation channels mediating fast
      excitatory transmission in the CNS.
AB  - In recent years, considerable progress in our understanding of the molecular
      events underlying excitatory synaptic transmission has been made. This progress
      was mainly achieved by technical advances, among them the patch-clamp technique
      in brain slices (Edwards et al., 1989), fast application of agonists (Franke et
      al., 1987), and cloning and functional expression of GluR channels of the nonNMDA
      type (e.g., Hollmann et al., 1989). A suitable model for studying excitatory
      postsynaptic currents (EPSCs) in the brain slice with patch-clamp techniques is
      the mossy fiber synapse on CA3 pyramidal cells of rat hippocampus (MF-CA3
      synapse). This synapse is located close to the cell soma and should provide
      almost ideal space-clamp conditions. A comparison of MF-CA3 EPSCs with the
      currents activated by fast application of glutamate on membrane patches isolated
      from CA3 cell somata suggests that the concentration of glutamate in the synaptic
      cleft during excitatory synaptic transmission is high (about 1 mM) and that the
      transmitter remains in the synaptic cleft only briefly (about 1 ms). It seems
      likely that desensitization influences the peak amplitude of the EPSC in several
      ways. Brief pulses of glutamate cause desensitization, from which the glutamate
      receptor channels recover only slowly, and micromolar ambient glutamate
      concentrations produce desensitization at equilibrium. From the functional
      properties of recombinant GluR channels, in situ hybridization data, and patch
      clamp experiments on different neuronal and nonneuronal cell types, a picture of
      the molecular identity of native channels emerges. In neurons of the hippocampus
      the pharmacological features of these channels were similar to recombinant
      channels assembled from subunits of the AMPA/kainate subtype which are strongly
      expressed in these cells. The native channels are characterized by outward
      rectification of the steady-state I-V and low Ca permeability, similar to
      recombinant channels containing the GluR-B subunit. This is consistent with the
      ubiquitous expression of this subunit in hippocampal neurones. In contrast, GluR
      channels from cerebellar glial cells, which uniquely in the central nervous
      system lack the expression of GluR-B subunits, show double rectification and high
      Ca permeability. The results suggest that the native functional nonNMDA glutamate
      receptor channels in the CNS are assembled form subunits of the AMPA/kainate
      subtype in a cell-specific way, with the functional properties of GluR channels
      in neurones being dominated by the GluR-B subunit.

PMID- 7505665
TI  - Mechanically sensitive, nonselective cation channels.
AB  - Mechanically sensitive channels (MSCs) are ubiquitous in plant and animal cells.
      They respond primarily to membrane tension, thus making them good transducers for
      forces derived from osmotic or hydraulic gradients and shear stress. They may
      also be modulated by membrane voltage and various ligands. MSCs are most commonly
      cation selective, passing calcium as well as monovalent ions, but some are K+
      selective, and a few are anion selective. MSCs occur at a density of about 0.2-5
      per microns2. The universal distribution and biophysical properties of MSCs make
      them the ideal mechanotransducers in a wide variety of cellular processes.

PMID- 7505666
TI  - Stretch-activated nonselective cation channels in urinary bladder myocytes:
      importance for pacemaker potentials and myogenic response.
AB  - Filling of the bladder with urine stretches the myocytes in the wall. Stretch
      activates nonselective cation channels (SACs) thereby constituting a pacemaking
      mechanism. Once action potentials are triggered, Ca2+ influx through nifedipine
      sensitive Ca2+ channels provides activator Ca2+ for the stretch-induced increase
      in wall tension (myogenic response). An additional component of myogenic response
      is independent of nifedipine and membrane potential; Ca2+ influx through SACs is
      large enough to induce Ca2+ release from intracellular stores.

PMID- 7505667
TI  - The in vivo effects of steel factor on natural killer lineage cells in murine
      spleen and bone marrow.
AB  - Steel factor (S1F), also known as stem cell factor, is a potent growth stimulator
      of hemopoietic progenitor cells. In the context of transplantation of hemopoietic
      cells to irradiated allogeneic hosts, natural killer (NK) cells exert restrictive
      control on hemopoietic cell proliferation, and are regularly found in elevated
      concentration in areas of intense hemopoiesis. The present study was designed to
      examine the effects with time of S1F in vivo on the numbers of NK cells,
      identified by the presence of the NK 1.1 surface molecule, in the spleen and bone
      marrow. Throughout the first 3 days of S1F exposure, NK cell numbers, in spite of
      rapid (1 day) and significant increases in the other hemopoietic cell lineages,
      did not change in either the spleen or the bone marrow. However, NK cells were
      increased 2-fold in both organs by 7 days of S1F exposure. At this time, immature
      granuloid and erythroid cells and the large lymphoid cells in the spleen had more
      than doubled their respective control numbers and in the bone marrow, immature
      granuloid cells increased by 47% of control levels. The presence of a late, but
      not early, influence of S1F on NK cells of the spleen and bone marrow suggests an
      indirect effect of S1F on this lineage, occurring only when S1F-stimulated
      hemopoiesis becomes sufficiently intense, providing, thus, an abundance of NK
      cell targets.

PMID- 7505668
TI  - Acute rejection of interferon-treated leukemia cells injected into lethally
      irradiated syngeneic mice.
AB  - Interferon (IFN) treatment of target cells can alter their susceptibility to
      natural resistance (NR), evidenced as in vitro 'natural killer' (NK) cell
      mediated lysis or as in vivo rapid cell clearance. This paper reports the
      consequence of direct in vitro treatment with IFN-alpha/beta or IFN-gamma on
      acute rejection of leukemia cells in lethally irradiated hosts. This type of
      rejection has the characteristics of NR, although it is specific and genetically
      regulated. The data were obtained injecting intravenously FLC (FLC-745 and FLC
      3C18 clones; H-2d) and EL-4 (H-2b) leukemia lines in lethally irradiated
      syngeneic mice and evaluating proliferation 4 days later by 125IUdR uptake.
      Overnight pretreatment with 100 U/ml of IFN-gamma protected tumor cells from NR
      induced rejection in mice. This was evident by higher 125IUdR incorporation in
      spleens of mice inoculated with IFN-gamma pretreated leukemia cells, as compared
      to that detected in the spleens of hosts injected with untreated cells, in mice
      with high levels of NR, but not in hosts depressed for NR. Treatment with 1,000
      U/ml of IFN-alpha/beta induced protection only of FLC-745 cells, injected in Poly
      I:C stimulated hosts. On the other hand, a lower 125IUdR uptake after IFN
      alpha/beta incubation, as compared with control cells, was evidenced with FLC-745
      and EL-4 lines inoculated in mice with normal or depressed NR. The IFN-induced
      alterations of leukemia cells to in vivo NR susceptibility were not associated
      with substantial changes of binding ability to NR effectors or of MHC-antigen
      expression.

PMID- 7505669
TI  - NusG alters rho-dependent termination of transcription in vitro independent of
      kinetic coupling.
AB  - To complement the recent discovery that rho-dependent termination in E. coli
      requires nusG protein in vivo, we have tested the effect of purified nusG protein
      on rho-dependent termination in vitro. With the well-characterized trp t'
      terminator of E. coli, and no other proteins than E. coli RNA polymerase and rho
      factor, nusG causes a proximal shift in the terminated RNA endpoints, compared to
      the endpoints generated by rho alone. The presence of nusG also enhances rho
      mediated termination on partially defective mutant trp t' templates. We rule out
      explanations such as a change in the kinetic coupling between rho and RNA
      polymerase or a nusG-mediated increase in the affinity of rho for RNA. We also
      detect no difference in the helicase rate of rho in the presence of nusG. Even
      assays with completely stalled and isolated ternary complexes indicate that rho
      is able to effect the release of RNA with the assistance of nusG at points
      preceding the most proximal release sites observed in the absence of nusG. Our
      observations support a model in which nusG acts as a component of the
      transcription complex, possibly interacting with both rho and RNA polymerase as
      it governs accessibility to the nascent transcript.

PMID- 7505670
TI  - The seemingly identical 7SK and U6 core promoters depend on different
      transcription factor complexes.
AB  - Fractions obtained from HeLa cell extracts were used to study RNA polymerase III
      catalyzed transcription from the human 7SK and mouse U6 RNA promoters in vitro.
      Although both genes depend on two almost identical core promoter elements (TATA
      box and PSE), different fractions were required. The 7SK promoter revealed full
      activity with the phosphocellulose B fraction alone. In contrast, efficient
      transcription from the U6 promoter depended on the additional presence of the C
      or D fraction. The analysis of the b1 and b2 subfractions (obtained by DEAE
      Sephadex chromatography) revealed that for both promoters the b1 and the
      phosphocellulose D fraction were mutually interchangeable. However, while both
      fractions were fully equivalent for the 7SK promoter, the U6 promoter revealed an
      additional requirement for the C fraction in the presence of the b1 fraction.
      Since the b1 and the D fractions enclose two different complexes of the TATA
      binding protein (TBP), B-TFIID and D-TFIID, our results indicate that
      functionally these two complexes are responsible for the observed differences in
      transcription of the 7SK and U6 genes.

PMID- 7505671
TI  - Expression of the carcinoma-associated keratin K6 and the role of AP-1 proto
      oncoproteins.
AB  - The normal pattern of keratin expression in epidermis is altered in carcinomas as
      well as in nonmalignant diseases such as psoriasis and wound healing. Under these
      circumstances, the transcription of differentiation-specific keratins K1 and K10
      is suppressed, whereas the activation- and hyperproliferation-associated keratins
      K6 and K16 are induced. Very little is known regarding transcriptional regulators
      involved in this switch. To investigate the nuclear factors that participate in
      regulation of expression of the K6 gene, we have characterized the binding sites
      for nuclear proteins on the promoter DNA of the K6 gene by gel retardation assays
      and site-specific deletion mutagenesis. We found four nuclear protein binding
      sites in the K6 gene promoter. Two are near the TATA box, but their ability to
      bind HeLa or keratinocyte nuclear extracts is independent of the TATA box-binding
      protein complex. The third binding site is a large palindrome. The sequences of
      these three sites do not correspond to any described target sequences for
      characterized transcriptional factors. The fourth is an AP-1 site, the target
      sequence for the proto-oncoproteins fos and jun. All four sites are independent
      of the previously characterized epidermal growth factor-responsive element, EGF
      RE. These findings suggest that there may be two parallel pathways of induction
      of K6 transcription. One proceeds through the EGF-RE, which may be involved in
      nonmalignant hyperproliferation processes; the other, through the AP-1 site and
      the fos-jun proto-oncoproteins, may be related to induction in malignant
      processes.

PMID- 7505672
TI  - A cluster of five nuclear proteins regulates keratin gene transcription.
AB  - A common feature of all epithelial cells is the presence of keratin proteins that
      assemble into an intermediate filament cytoskeletal network. Whereas other cell
      types often use a specific master transcription factor to coordinate cell type
      specific transcription, analysis of transcriptional regulation of keratin genes
      suggests that specific groupings of widely expressed transcription factors,
      acting on clusters of recognition elements in the promoter regions, confer
      epithelia-specific transcription. We define such a cluster of three sites that
      binds five transcription factors in the human K5 keratin gene. Within this
      cluster, an unusual Sp1 site binds the Sp1 transcription factor and two
      additional proteins. Flanking the Sp1 site are an AP2 site and another sequence,
      Site A; each binds a transcription factor. Similar clusters of recognition sites
      for the same five transcription factors have been also identified in other
      keratin genes. Such clusters may play a role in epithelia-specific expression of
      keratins.

PMID- 7505673
TI  - Screening for prostate cancer. How can patients give informed consent?
AB  - Many urologists in North America are increasingly enthusiastic about prostatic
      cancer screening. Annual digital rectal examination is almost universally
      endorsed, and prostate-specific antigen testing is favored by most. But doctors
      really should not screen by either method without patients' informed consent.
      However, the information required for informed consent is complex and
      contradictory, difficult for physicians to give and for patients to absorb.

PMID- 7505674
TI  - Transport and accumulation of lipophilic dye cations at the mitochondria of HeLa
      cells in situ.
AB  - The vital staining of mitochondrial in HeLa cells was investigated with various
      cationic styrylindolenines and indocarbocyanines. These dyes differed greatly in
      their lipophilic properties which were characterized by the partition coefficient
      Po/w between octanol (o) and water (w). The microspectra of the stained cells
      were measured in absorption and fluorescence and indicated that the dyes were not
      metabolized within the cells. In addition, the spectra suggested that the dye
      molecules were accumulated in strongly lipophilic areas of the mitochondria.
      Investigations of the mitochondrial ultrastructure as well as the respiratory
      activity and the rate of cell division indicated that the extremely lipophilic
      enzymes of the oxidative phosphorylation in the inner mitochondrial membrane were
      the favoured binding partners. The kinetics of dye accumulation was investigated
      with the concentration jump method. The flow Jo at the start of dye incubation at
      time t = 0 and the maximum fluorescence intensity Imax at t = infinity were
      measured. The influence of respiratory inhibitors, uncouplers, and ionophores on
      Jo and Imax were also investigated. The flow Jo at t = 0 describes the transfer
      of the dye through the cell membrane. Jo strongly depended on the lipophilicity
      of the dye molecules. With growing Po/w Jo first linearly increased and later
      leveled off. The same effect was observed in kinetic studies of the dye transfer
      in the model system octanol/water. The maximum concentration of bound dye
      molecules is given by Imax. It depended on the transmembrane potential (TMP) at
      the inner mitochondrial membrane as well as the hydrophobic interactions of the
      dye with the lipophilic substrates of the inner membrane. The influence of TMP
      and Po/w on the dye accumulation are discussed in detail. Both trans-membrane
      potential and hydrophobic interactions are involved in strong dye binding at the
      mitochondria.

PMID- 7505675
TI  - Lipopolysaccharide (LPS) binding in subpopulations of mouse peritoneal
      macrophages.
AB  - Lipopolysaccharide-binding sites of mouse peritoneal macrophages were
      demonstrated by means of immunogold technique. Resident peritoneal macrophages
      identified by peroxidatic activity in the nuclear envelope and in the rough
      endoplasmic reticulum show moderate and constant specific binding of bacterial
      lipopolysaccharide from E. coli (026:B6) to cell surface structures. Monocyte
      derived macrophages with peroxidatic activity in cytoplasmic granules are
      characterized by a broad binding pattern. A high percentage of monocyte-derived
      macrophages bind large amounts of LPS-gold particles whereas some others bind
      only less lipopolysaccharide. This is a further hint for the existence of
      monocyte subpopulations. The different binding patterns of LPS after fixation and
      the inhibitor-ability of this binding supports the hypothesis that LPS binding is
      at least partly receptor-mediated.

PMID- 7505676
TI  - Handling reagents in the PCR laboratory.

PMID- 7505677
TI  - A PCR-based method for the analysis of human CD44 splice products.
AB  - CD44 is a transmembrane glycoprotein involved in the interaction between cells
      and extracellular matrix. Several variant forms of CD44 exist, which differ from
      each other in the composition of both the intra- and extracellular domain of the
      protein. Post-translational modification and alternative RNA processing are
      responsible for this variation. Recently, it was found that certain variant CD44
      proteins, containing extra sequences in the extracellular domain of the protein,
      are involved in metastatic spread of tumor cells. Variant CD44 proteins are also
      involved in immunological functions of T and B cells. A large variety of
      alternatively spliced CD44 mRNAs can be expressed by cells. We have developed a
      method for the analysis of CD44 mRNAs present in the cell. This reverse
      transcription-polymerase chain reaction (RT-PCR)-based method can be used to
      analyze the exon composition of each major CD44 mRNA species present in the cell.
      In this study we describe the analysis of CD44 mRNAs isolated from six different
      human cell lines.

PMID- 7505678
TI  - Quantitation of tropoelastin mRNA and assessment of alternative splicing in human
      skin fibroblasts by reverse transcriptase-polymerase chain reaction.
AB  - We have developed a reverse transcriptase-polymerase chain reaction (RT-PCR)
      assay for the quantitative measurement of levels of tropoelastin mRNA in total
      RNA preparations from skin fibroblasts. This method facilitates the reproducible
      detection of low abundance tropoelastin mRNA in the range of 10-1000 copies per
      cell. The procedure is based on a competitive RT-PCR assay where a tropoelastin
      cDNA-derived internal RNA standard is cotranscribed and coamplified together with
      the sample derived-endogenous target mRNA. In addition, RT-PCR of several domains
      of tropoelastin mRNA, followed by DNA sequence analysis of asymmetric PCR
      products, revealed a previously unknown pattern of alternate exon usage at the 3'
      end of the tropoelastin gene in human skin fibroblasts.

PMID- 7505679
TI  - Controls for validation of relative reverse transcription--polymerase chain
      reaction assays.

PMID- 7505680
TI  - Knowledge-based model building of proteins: concepts and examples.
AB  - We describe how to build protein models from structural templates. Methods to
      identify structural similarities between proteins in cases of significant,
      moderate to low, or virtually absent sequence similarity are discussed. The
      detection and evaluation of structural relationships is emphasized as a central
      aspect of protein modeling, distinct from the more technical aspects of model
      building. Computational techniques to generate and complement comparative protein
      models are also reviewed. Two examples, P-selectin and gp39, are presented to
      illustrate the derivation of protein model structures and their use in
      experimental studies.

PMID- 7505681
TI  - Toward computational determination of peptide-receptor structure.
AB  - We introduce a method for docking small flexible ligands of the size of
      dipeptides and phosphocholine and test it against crystallographic complexes. We
      then show how the method can be used as the basis for a strategy for solving the
      much more difficult problem of docking fully flexible peptides in the 8-10
      residue size range. After developing the method we apply it to peptide-MHC class
      I systems and find that the predictions are in accord with biological and
      crystallographic data.

PMID- 7505682
TI  - Design of a functional calcium channel protein: inferences about an ion channel
      forming motif derived from the primary structure of voltage-gated calcium
      channels.
AB  - To identify sequence-specific motifs associated with the formation of an ionic
      pore, we systematically evaluated the channel-forming activity of synthetic
      peptides with sequence of predicted transmembrane segments of the voltage-gated
      calcium channel. The amino acid sequence of voltage-gated, dihydropyridine (DHP)
      sensitive calcium channels suggests the presence in each of four homologous
      repeats (I-IV) of six segments (S1-S6) predicted to form membrane-spanning, alpha
      helical structures. Only peptides representing amphipathic segments S2 or S3 form
      channels in lipid bilayers. To generate a functional calcium channel based on a
      four-helix bundle motif, four-helix bundle proteins representing IVS2 (T4CaIVS2)
      or IVS3 (T4CaIVS3) were synthesized. Both proteins form cation-selective
      channels, but with distinct characteristics: the single-channel conductance in 50
      mM BaCl2 is 3 pS and 10 pS. For T4CaIVS3, the conductance saturates with
      increasing concentration of divalent cation. The dissociation constants for Ba2+,
      Ca2+, and Sr2+ are 13.6 mM, 17.7 mM, and 15.0 mM, respectively. The conductance
      of T4CaIVS2 does not saturate up to 150 mM salt. Whereas T4CaIVS3 is blocked by
      microM Ca2+ and Cd2+, T4CaIVS2 is not blocked by divalent cations. Only T4CaIVS3
      is modulated by enantiomers of the DHP derivative BayK 8644, demonstrating
      sequence requirement for specific drug action. Thus, only T4CaIVS3 exhibits pore
      properties characteristic also of authentic calcium channels. The designed
      functional calcium channel may provide insights into fundamental mechanisms of
      ionic permeation and drug action, information that may in turn further our
      understanding of molecular determinants underlying authentic pore structures.

PMID- 7505683
TI  - [Ultrastructure of the rat blood- brain barrier after hypoxia and administration
      of hydrophobized RNA].

PMID- 7505684
TI  - Inhibition of bovine leukocyte thioltransferase by anti-inflammatory drugs and
      anti-histaminic drugs.
AB  - Thioltransferase was partially purified from bovine leukocyte using sonication,
      heat treatment at pH 5.1, Sephadex G-50 gel filtration and isoelectric focusing
      techniques. Isoelectric point (pI) of 8.3 for leukocyte thioltransferase was
      quite different from pI of 6.5 for erythrocyte enzyme. Bovine leukocyte
      thioltransferase was employed in a study on the influence of 12 anti-inflammatory
      drugs and 7 anti-histaminic drugs. Piroxicam which is a well-known anti
      inflammatory drug demonstrated the most powerful inhibitory effect on enzyme
      activity. Inhibition of piroxicam was noncompetitive, and the Ki value measured
      55.0 microM in the experiment involving bovine leukocyte enzyme. Tranilast which
      is a typical anti-histaminic drug most strongly inhibited the enzyme activity and
      the Ki value of the medicine was 20.3 microM (noncompetitive). Bovine liver and
      erythrocyte thioltransferases also were effectively inhibited by both medicines
      similar to leukocyte enzyme.

PMID- 7505685
TI  - Nifedipine and nicardipine potentiate glucagon-stimulated glycogenolysis in
      primary cultures of rat hepatocytes.
AB  - The effects of two calcium channel blockers, nifedipine and nicardipine, on
      glucagon-stimulated glycogenolysis in primary cultures of rat hepatocytes were
      examined in vitro. When nifedipine and nicardipine (10(-7)-10(-6) M) were added
      to the incubation mixture with various concentrations of glucagon (10(-10)-10(-6)
      M), these dihydropyridine calcium channel blockers significantly potentiated the
      glycogenolytic action of glucagon by increasing intracellular cAMP levels. 1
      Methyl-3-isobutylxanthine (IBMX), caffeine and papaverine, which is known to
      inhibit cAMP phosphodiesterase, also potentiated the stimulatory effect of
      glucagon on the glycogenolysis in a dose-dependent manner. Parallel to the
      potentiation of glycogenolysis, IBMX also increased the glucagon-stimulated
      intracellular cAMP levels in a dose-dependent manner. These results suggest that
      the mechanism of potentiation of the glucagon-stimulated glycogenolysis by
      nifedipine and nicardipine is related to the known inhibition of cAMP
      phosphodiesterase by these agents.

PMID- 7505686
TI  - Pharmacological evidence for involvement of excitatory amino acids in aversive
      responses induced by intrathecal substance P in rats.
AB  - Rats given an intrathecal injection of substance P (0.3-10 nmol) or any of the
      excitatory amino acid agonists, N-methyl-D-aspartate (NMDA, 1-10 nmol), kainate
      (1 and 3 nmol) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, 0.3
      3 nmol), showed biting or licking the hind paws, scratching with the hind paws
      (only after substance P) and vocalization (only after excitatory amino acid
      agonists). The intrathecal co-administration of the NMDA antagonist, 2-amino-5
      phosphonovaleric acid (APV, 10 nmol), inhibited behavioral responses to NMDA (10
      nmol) and substance P (10 nmol) but not to kainate (3 nmol). Co-administration of
      the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 nmol),
      suppressed responses to kainate (3 nmol), AMPA (3 nmol) and substance P (10 nmol)
      but not to NMDA (10 nmol). Co-administration of the substance P antagonist, CP
      96,345 (3 nmol), inhibited the behavioral responses to substance P (10 nmol), but
      not to NMDA (10 nmol), kainate (3 nmol) and AMPA (3 nmol). The results suggest
      that the aversive behavior induced by intrathecal NMDA and non-NMDA agonists is
      mediated by activation of the corresponding glutamate receptors, but not by NK-1
      receptors, and that the behavioral action of intrathecal substance P is mediated
      not only by direct activation of NK-1 receptors but also indirectly by NMDA and
      non-NMDA receptors for glutamate.

PMID- 7505687
TI  - Distinct effects of clinically used anthracycline antibiotics on ras oncogene
      expressed cells.
AB  - Doxorubicin, pirarubicin, and FAD-104, but not aclarubicin or MX 2, flattened the
      morphology of NIH3T3 cells that had been transformed by human H-ras and K-ras.
      The effect appeared on almost all cells, as early as 2 d following exposure to
      the antibiotics at concentrations inhibiting cell growth by 50% or more. The
      morphological alteration accompanied other normal cell phenotypes, such as the
      restoration of actin stress fibers, anchorage dependence of cell growth and an
      increase in nucleoside diphosphate (NDP) kinase activity. NIH3T3 cells
      transformed by src and other tumor cell lines responded less prominently, if at
      all.

PMID- 7505688
TI  - Endotoxin-induced enhancement of angiotensinogen synthesis in the liver:
      decreased response following repeated endotoxin exposure.
AB  - To understand the mechanisms responsible for lipopolysaccharide (LPS)-induced
      enhancement of angiotensinogen synthesis in the liver, studies were carried out
      in rats with repeated doses of LPS. The administration of sublethal dose (50
      micrograms, i.p.) of LPS to rats resulted in increase in serum levels of tumor
      necrosis factor (TNF) and interleukin-6 (IL-6), which attained their maximal
      levels by 1 and 2-4h, respectively. Serum levels of angiotensinogen and alpha 2
      macroglobulin, a typical acute-phase protein in the rat, were also increased by a
      primary LPS challenge, and their maximal levels for the formation of TNF and IL-6
      were delayed with peaks at 12 and 48 h, respectively. Repeated i.p.
      administration of LPS (50 micrograms/d) for 5 consecutive days induced a
      hyporesponsiveness to its subsequent administration in terms of increasing serum
      TNF, IL-6 and alpha 2-macroglobulin. In these LPS-tolerant rats, either LPS
      induced elevation of angiotensinogen concentration in serum or angiotensinogen
      mRNA levels in liver was completely eliminated. Angiotensinogen synthesis in rat
      hepatoma H4 cells was enhanced in vitro by the addition of sera which had been
      collected 2 or 4 h after a primary injection of LPS, while not by sera collected
      from LPS-pretreated rats after a secondary LPS exposure. These results indicate
      that LPS-induced enhancement of angiotensinogen synthesis in the liver is
      desensitized in rats after repetitive LPS exposure, presumably by the failure of
      LPS-induced IL-6 production.

PMID- 7505689
TI  - Direct sequencing of the complete CFTR gene: the molecular characterisation of
      99.5% of CF chromosomes in Wales.
AB  - We have performed an extensive mutation analysis on 184 CF families in Wales. In
      our previous study, mutations on 329/369 CF chromosomes were identified after
      screening for delta F508 and sixteen other mutations. To identify the mutations
      on the remaining 40 uncharacterized CF chromosomes, we have carried out direct
      DNA sequencing over the complete coding region, intron splice sites, and part of
      the promoter region of the CFTR gene. During this study we have designed a set of
      internal sequencing primers which allow clear sequencing through the
      aforementioned regions. Sequence analysis revealed 15 further mutations (4 of
      which are novel), and 10 previously described polymorphisms. In total, we have
      identified 29 mutations, the distribution of which provides further insight into
      the functional domains of the CFTR protein. We have characterised 99.5% of the CF
      chromosomes (365/367, one sample degraded). In order to ascertain accurate
      frequency data for the Welsh population, CF families with at least 3 'Welsh'
      grandparents were strictly regarded as 'Welsh'. Of these 91 families, delta F508
      accounts for 71.6%, 621 + 1G-->T 6.6% and 1898 + 1G-->A 5.5%. The implications
      for CF population screening in Wales are discussed.

PMID- 7505690
TI  - Genotype analysis of adult cystic fibrosis patients.
AB  - To assess the relationship between the genotype and phenotype of adult CF
      patients we have selected from a group of 512 CF patients attending centres in
      France, all these of greater than 35 years. We have analysed the entire coding
      sequence of their CFTR genes. The complete genotype was determined in 7 of the 8
      patients and clinical data regarding pancreatic, respiratory and reproductive
      function were carefully evaluated. All these patients are compound heterozygote,
      seven carrying the delta F508 and one the G542X on one allele. The other allele
      carried is: (i) a missense mutation located in exons coding for transmembrane
      region in five patients [R334W (1); I336K (2); R117H (1); H1054D (1)]; (ii) a
      splice mutation in two patients [2789 + 5G-->A], (iii) an uncharacterised
      mutations in one patient. These results strongly suggest less severe CF phenotype
      to be associated with these mutations and strengthen the hypothesis that less
      severe phenotype are genetically determined.

PMID- 7505691
TI  - A severe phenotype in mice with a duplication of exon 3 in the cystic fibrosis
      locus.
AB  - To develop an animal model for cystic fibrosis (CF), targeted gene disruption in
      embryonic stem (ES) cells was used to generate a duplication of exon 3 (cftrm1Bay
      allele) of the mouse CF gene. ES cells containing this mutation were used to
      generate chimeric animals that transmitted the mutant allele through the
      germline. Homozygous mutant animals display a severe phenotype, with
      approximately 40% dying within 1 week from intestinal obstruction. RNAase
      protection analysis of the cftrm1Bay allele did not detect any normal mRNA (< 1
      2% of wild-type) in mutant animals. Pathologic changes in the intestines from
      mutant mice included mucus accumulation in the crypts and intestinal lumen,
      dilatation of the bases of the crypts, enlargement of goblet cells, and the
      presence of concretions in the crypts or between the villi. Changes were also
      present in the mucosal glands of the pharynx and the minor sublingual glands,
      where dilatation of acini and accumulation of eosinophilic material were evident.
      Atrophy of acinar cells that may be secondary to nutritional deficiency and mild
      inflammation in the main pancreatic duct were present in the pancreas of mutant
      animals. No changes were noted in the lung, trachea, liver, or male reproductive
      tract of mutant animals, and mutant males were fertile. Homozygous mutant mice
      showed defects in cAMP-mediated ion transport both in ileum and in cultured fetal
      tracheal explants. Thus, an additional mouse model for CF has been generated that
      should prove useful for the understanding of the pathogenesis and the development
      of treatments for CF.

PMID- 7505692
TI  - Nasal epithelial ion transport and genetic analysis of infertile men with
      congenital bilateral absence of the vas deferens.
AB  - It has been suggested that congenital bilateral absence of the vas deferens
      (CBAVD), an important cause of male infertility, is a variant of cystic fibrosis
      (CF). This study describes a defect in chloride conductance across the nasal
      epithelium of subjects with CBAVD which is dissimilar to that found in patients
      with CF. It also demonstrates normal sodium transport across the nasal epithelium
      in these men, in contrast to patients with CF who exhibit increased sodium
      absorption. The increased frequency of CFTR mutations in these men implicates the
      CFTR gene in the pathogenesis of this disorder. Genetic analysis of men with
      CBAVD who were heterozygous for a known CFTR mutation failed to identify a second
      mutation within any of the exons or introns of the CFTR gene. These results
      demonstrate that most men presenting with CBAVD are not compound heterozygotes
      for mutations within the CFTR gene and can be distinguished from individuals with
      atypical or asymptomatic CF on the basis of the bioelectric properties of their
      nasal epithelium. We postulate that mutations in the promoter region or at other
      regulatory sites of the CFTR gene may be responsible for the CBAVD phenotype in a
      proportion of cases.

PMID- 7505693
TI  - Two novel mutations in the transmembrane domains of the CFTR gene in subjects of
      Sardinian descent.

PMID- 7505694
TI  - Identification of a new missense mutation (P205S) in the first transmembrane
      domain of the CFTR gene associated with a mild cystic fibrosis phenotype.

PMID- 7505695
TI  - Maternal autoantibodies and congenital heart block: no evidence for the existence
      of a unique heart block-associated anti-Ro/SS-A autoantibody profile.
AB  - One of the rare examples of the transfer of autoimmune disease from mother to
      (unborn) child is the neonatal lupus syndrome. This syndrome comprises the
      development of fetal heart disease (congenital heart block) or neonatal skin rash
      and is specifically associated with maternal anti-Ro/SS-A autoantibodies.
      Previous studies have suggested that especially maternal autoantibody reactivity
      against the 52 kDa protein of the Ro/SS-A antigen and/or against the La/SS-B
      antigen is responsible for the development of congenital heart block (CHB). To
      determine the CHB-associated antibody response in more detail, we analysed the
      presence of autoantibodies in sera from mothers of children with isolated heart
      block. All 14 mothers of children with congenital heart block were positive for
      anti-Ro/SS-A antibodies. Remarkably, their antibody profile, including
      recognition of different Ro/SS-A proteins and autoantibody levels against these
      proteins, did not differ from anti-Ro/SS-A positive mothers of healthy children.
      In contrast, all 8 anti-Ro/SS-A negative mothers had children with acquired heart
      block. We conclude from our data that maternal anti-Ro/SS-A antibodies are
      essential for CHB but that fine analysis of this autoantibody response does not
      predict the occurrence of CHB.

PMID- 7505696
TI  - [The effect of the neuropeptide galanin on active avoidance in rats].
AB  - Administration of galanin into the lateral brain ventricles induced a dose
      dependent impairment of memory in the active avoidance test in rats. Atropine
      both induced the impairment of memory and potentiated the galanin amnestic
      effect. Naloxone had no such action as well as ketamine. Galanin seems to impair
      memory via suppressing cholinergic and activating opioid peptidergic transmission
      in the CNS.

PMID- 7505697
TI  - [The importance of the plasma proteins of the blood in maintaining the relative
      constancy of its hydrolytic properties].
AB  - Effects of hypervolemia, dehydration, activation and inhibition of urine
      formation, i. v. administration of amylase and pepsinogen, experimental acute
      pancreatitis upon amylolytic activity of blood plasma, contents of pepsinogen in
      it, amylase and pepsinogen within the blood plasma protein factions, and
      excretion of enzymes with the urine, were studied in dogs. The data obtained
      suggest an important role of interconnection between amylase and pepsinogen with
      the plasma proteins in their renal and extrarenal excretion from the organism and
      in maintenance of a relative constancy of the contents and activity of enzymes in
      the blood. The affinity of the plasma proteins to their stains can indirectly
      characterise the transport capacity of the proteins in respect to amylase and
      pepsinogen.

PMID- 7505698
TI  - Effect of modification of carbohydrate side chains on the reactivity of
      antibodies with core-protein epitopes of the MUC1 gene product.
AB  - The product of the MUC1 gene, the polymorphic epithelial mucin (PEM), contains a
      large domain consisting of tandem repeats of 20 amino acids. Each repeat contains
      five potential sites for O-glycosylation, suggesting that this region forms a
      scaffold for the attachment of the O-linked carbohydrate which makes up more than
      50% of the molecule. A number of monoclonal antibodies have been shown to
      recognize core-protein epitopes within the tandem repeat domain. One such
      antibody, SM3, reacts with the mucin expressed by breast carcinomas but shows
      little or no reaction with normal resting or lactating breast. Using primary
      mammary epithelial cells (HuME), an immortalized cell line derived from HuME
      (MTSV1-7) and a breast carcinoma cell line (BT20) the influence of the
      carbohydrate side chains on the binding of antibodies to core-protein epitopes
      has been investigated. We unequivocally show that the masking of the SM3 epitopes
      in normal breast epithelial cells is due to the carbohydrate side chains. In
      addition we demonstrate that the binding of two other antibodies (HMFG1, HMFG2)
      to core-protein epitopes is influenced by the carbohydrate side chains. The
      binding of HMFG-1 is particularly affected by sialic acid whereas the binding of
      HMFG2 is influenced by the length of the oligosaccharide side chains.
      Furthermore, inhibited elongation of O-linked carbohydrate side chains does not
      seem to interfere with the cell trafficking of the mucin to the cell surface.

PMID- 7505699
TI  - Transport of cytoskeletal proteins in axons of hippocampal pyramidal cells.
AB  - Axonal transport of cytoskeletal proteins has not yet been extensively studied in
      the brain proper, in contrast to the peripheral nerves and optic nerves. The
      authors have developed a means for the study of transport of cytoskeletal
      proteins in axons of hippocampal pyramidal cells. Proteins of intrinsic neurons
      of the dorsal hippocampus were labeled by microinjection of 35S methionine, and
      the subsequent transport of labeled proteins was characterized in the axons
      projecting into the fimbria-fornix. A peak of labeled proteins was present in the
      fimbria-fornix at 4-12 days after labeling, corresponding to transport rates 0.2
      0.7 mm/day. The most abundant proteins at each time studied exhibited one
      dimensional electrophoretic mobilities of actin and tubulin; neurofilaments were
      less intensely labeled. The observed specializations of cytoskeletal transport,
      especially the paucity of tubulin transport at rates of 2-4 mm/day, may
      predispose hippocampal pyramidal cells to accumulate tubulin and microtubule
      associated proteins in their cell bodies in various disease states.

PMID- 7505700
TI  - The regulation of neurofilament protein dynamics by phosphorylation: clues to
      neurofibrillary pathobiology.
AB  - Neurofilament proteins are continuously modified during their lifetime by a
      succession of protein kinases and phosphatases. Site-specific phosphorylation or
      dephosphorylation within different polypeptide domains of each neurofilament
      subunit is now believed to regulate such behaviors of neurofilaments as subunit
      polymerization and exchange, axonal transport, interactions with other
      cytoskeletal proteins and degradation. Local regulation of phosphorylation events
      could account for variations in the size, morphology and dynamics of the
      neurofilament network in different regions of the neuron. The apparent greater
      plasticity of the neurofilament network in regions like the perikaryon, initial
      segment and nodes along the axon may provide some insight into the vulnerability
      of these regions in neurofibrillary disease.

PMID- 7505701
TI  - The salivary glands of the vector mosquito, Aedes aegypti, express a novel member
      of the amylase gene family.
AB  - Several cDNA clones with similarity to alpha-amylases have been characterized
      from a library made from adult female salivary gland RNA isolated from the vector
      mosquito, Aedes aegypti. The corresponding gene, designated Amylase I (Amy I), is
      expressed specifically in the proximal-lateral lobes of the adult female salivary
      gland, a pattern overlapping that of another gene, Mal I, involved in
      carbohydrate metabolism. The deduced amino acid sequence of Amy I indicates that
      this gene encodes a protein, approximate M(r) = 81,500, that appears to be a
      novel member of the amylase gene family. The mosquito protein contains a putative
      signal peptide for secretion and several consensus sites for asparagine-linked
      glycosylation. The Amy I protein shows significant similarity to invertebrate and
      vertebrate amylases including the conservation of four reactive and substrate
      binding sites. However, the amino-terminal region of the Amy-I protein is unique
      to the mosquito. Similarity with the Drosophila melanogaster protein is evident
      only after the first 260 amino acids in the mosquito sequence. The identification
      of this gene and its expression pattern adds to the observed relationship between
      spatial-specific gene expression in the female salivary glands and the specific
      feeding mode of the adult mosquito.

PMID- 7505702
TI  - Congenital left ventricular outflow tract obstruction.
AB  - Congenital obstruction of the left ventricular outflow tract remains a
      significant problem. Obstruction may involve the subvalvar, valvar or supravalvar
      portion of the aortic valve complex. Congenital valvar stenosis presenting in the
      neonatal period represents a spectrum of disorders ranging from the hypoplastic
      left heart syndrome to almost normal hearts. Preoperative echocardiography may
      allow the selection of infants who are suitable for biventricular repair, with
      the therapeutic options including open valvotomy and balloon valvotomy, but the
      determination of the optimal method of treatment will require long term follow up
      data. Subvalvar obstruction may be discrete or diffuse, and the extent will
      determine the appropriate therapy. Discrete membranes may be managed by a simple
      excision while diffuse involvement of the subvalvar region may require a more
      extensive reconstructive procedure such as the Konno procedure. Supravalvar
      aortic stenosis is the least common form of aortic stenosis and may be associated
      with abnormalities of the pulmonary arteries. Treatment is often palliative
      rather than corrective with all types of congenital left ventricular outflow
      tract obstruction, and many patients will require reoperations, especially those
      with valvar and subvalvar obstruction. The lack of long term follow up data for
      patients treated in the neonatal period makes the choice of an optimal therapy
      difficult. New methods of valve replacement such as the pulmonary autograft may
      improve long term results.

PMID- 7505703
TI  - Turbulence intensity in aortic stenosis: frequency characteristics and effects of
      alterations in left ventricular function.
AB  - Turbulent blood flow can occur downstream from a stenosis. The purpose of this
      study was to quantitate turbulence intensity and its frequency characteristics in
      the ascending aorta in adult patients with and without valvular stenosis, and to
      use extrasystoles to analyze the effects of changes in left ventricular function
      on turbulence. Turbulence intensity was determined from the digitized, high
      frequency oscillations seen in high fidelity pressure recordings of 25 patients
      with valvular aortic stenosis. The intensity of turbulence was quantitated as the
      root-mean-square (mmHg) of pressure fluctuations and as the total spectral power
      (mmHg2/beat) of the frequency spectrum between 25 Hz and 400 Hz. Frequency
      characteristics were summarized by the mean and median frequency of spectral
      power and partitioning the spectrum into 25 Hz segments. Ten adult patients
      without aortic valve or outflow tract abnormalities served as controls. Adult
      patients with aortic stenosis had significantly more turbulence in the ascending
      aorta than controls (total spectral power 1577 +/- 450 mmHg2 vs. 198 +/- 22
      mmHg2, p < 0.01). Furthermore, the frequency distribution in aortic stenosis was
      biased towards higher frequencies (mean frequency 35 +/- 14 Hz vs 54 +/- 2 Hz, p
      < 0.001). Turbulence intensity in aortic stenosis demonstrated beat to beat
      modulation by left ventricular function. The total spectral power of a sinus beat
      was 1888 +/- 762 mmHg2, and fell to 137 +/- 63 mmHg2 in a weak premature beat,
      and rose to 3618 +/- 1178 mmHg2 in a potentiated post- extrasystolic beat (p =
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505704
TI  - Ethical Issues in Patient Care and Disease Management. Proceedings of the 3rd
      International Symposium on Amyotrophic Lateral Sclerosis/Motor Neurone Disease.
      Solihull, United Kingdom, 2-4 November, 1992.

PMID- 7505705
TI  - Ethics and the clinician: the daily experience with motor neurone disease.
AB  - Ethical issues in health care are typically perceived as arising from extreme
      situations which do not usually confront the average clinician. However,
      knowingly or otherwise, clinicians working with motor neurone disease deal daily
      with ethical issues in the form of value judgements, the application of choice
      limiting principles and the language of clinician-patient interaction.

PMID- 7505706
TI  - Ethical issues in palliative care--an overview.
AB  - There are many ethical decisions to be made during palliative care of a patient
      with motor neurone disease. These may concern the physical and psychosocial care
      of the patient and will become highlighted when death approaches. By close
      involvement of the patient and his/her family with the interdisciplinary team the
      most appropriate decisions on the patient's care can be made.

PMID- 7505707
TI  - Research and the associations: an era for partnership.
AB  - A growing volume of research is being conducted into amyotrophic lateral
      sclerosis/motor neurone disease, driven in part by a perceived rise in incidence
      of the disease. This increase in research coincides with the emergence of the
      voluntary associations. Originally critical of the lack of research, the
      associations have started to raise funds for a variety of studies. Many of these
      require the active involvement of patients, and, given the relatively small
      numbers, there are dangers of the associations, research and good clinical care
      becoming too closely interdependent. There are also dangers of pharmaceutical
      companies and the voluntary associations being put under pressure to produce
      results extremely quickly. As well as having a valuable part to play in research,
      the voluntary associations are also involved in patient education, and in trying
      to spread the word on which available options are the subject of 'informed
      choice'.

PMID- 7505708
TI  - Multidisciplinary management from day one: the Neuro-care approach to motor
      neurone disease.
AB  - The Neuro-care approach offers a holistic, multidisciplinary, patient-centred,
      continuous strategy of care to unselected groups of neurological patients and
      their families including those with motor neurone disease (MND). The strategy for
      MND patients is an adapted version of one piloted on patients with Parkinson's
      disease. Between April 1990 and September 1992 12 MND patients were diagnosed, of
      whom five have died. The main features of the care strategy and the guidelines
      for giving the diagnosis are described. The characteristics of the patient group
      are identified and the high level of team activity vis-a-vis other patient groups
      is noted. The maintenance of patients in the community and the lack of resort to
      permanent institutional care are also recorded. Ethical issues arising during the
      project are discussed and the problems of measuring outcomes of care are
      acknowledged. General conclusions for MND management are drawn.

PMID- 7505709
TI  - Breaking bad news in amyotrophic lateral sclerosis.
AB  - There are many difficulties of communication with patients with amyotrophic
      lateral sclerosis (motor neurone disease). In France, most physicians have a
      policy of keeping the fact of this diagnosis from both patients and relatives.
      This paper describes an alternative approach based on open communication, and
      applies that principle to handling issues of communication associated with
      various aspects of four different topics: the diagnosis itself, the development
      of handicap, swallowing difficulties, and respiratory difficulties.

PMID- 7505710
TI  - A review of dysphagia in four cases of motor neurone disease.
AB  - Dysphagia is a common and distressing problem in motor neurone disease. This
      paper examines some of the strategies available for managing patients with
      dysphagia, and illustrates these with four contrasting case histories. The
      factors which influence the decision making process in patients with dysphagia
      are also discussed.

PMID- 7505711
TI  - Decision-making in the respiratory care of amyotrophic lateral sclerosis: should
      home mechanical ventilation be used?
AB  - As respiratory function starts to deteriorate in those with amyotrophic lateral
      sclerosis, one of the principal questions that has to be answered is whether it
      it is appropriate to provide ventilatory support. Although expensive, it is
      perfectly feasible to provide this at home, and this article examines many of the
      issues surrounding home mechanical ventilation.

PMID- 7505712
TI  - Dying at home: a way of maintaining control for the person with ALS/MND.
AB  - Control is a key issue for patients with amyotrophic lateral sclerosis, and
      caring for them in their own homes is often an essential part of remaining in
      control. This goal can usually be achieved if all resources are correctly used.

PMID- 7505713
TI  - Palliative care and taboos within motor neurone disease.
AB  - Taboos, whether held by professional carers, patients or families have the
      capacity to influence a whole range of choices that must be made during the
      course of any illness. In the case of motor neurone disease, decisions regarding
      if, when and how to break bad news, the place of care (home, hospital or
      hospice), the introduction of aids and devices, and, ultimately, choices
      regarding the place of death, will all be influenced by a range of taboos. If
      professional carers have major unresolved issues concerning their own mortality,
      it is unlikely that they will be able to truly stand alongside those who are
      facing their own imminent death. In discussing taboos, essentially what is of
      concern is attitudes. A basic change in attitudes is required if we are to stop
      viewing patients with incurable illness as some kind of medical failure.

PMID- 7505714
TI  - Mechanisms of action and therapeutic potential of adenosine and its analogues in
      the treatment of cardiac arrhythmias.
AB  - Adenosine is a purine nucleoside found in every cell of the human body. In
      addition to its well-established role in cellular metabolism, extracellular
      adenosine exerts pronounced effects on the cardiovascular system. These effects,
      mediated by specific cell surface receptors, include a negative chronotropic
      effect on cardiac pacemakers, a negative dromotropic effect on atrioventricular
      nodal conduction, an antiadrenergic effect, and a vasodilatory effect on blood
      vessels. In addition, adenosine can attenuate platelet aggregation and neutrophil
      activation and alter cardiac metabolism. Its electrophysiologic effects on
      atrioventricular nodal conduction constitute the rationale for the use of
      adenosine as an antiarrhythmic drug for the acute management of paroxysmal
      reentrant supraventricular tachycardias involving the atrioventricular node, as
      well as for its use as a diagnostic tool in broad complex tachycardias and in
      preexcitation. The antiadrenergic action of adenosine explains its potential use
      in the acute management of catecholamine-dependent ventricular tachycardias.
      Several of the other effects of adenosine suggest the use of this compound as
      well as its analogues as cardioprotective agents in the setting of myocardial
      ischemia (occlusion then reperfusion of coronary vessels, cardioplegia, coronary
      angioplasty, thrombolysis, and so forth).

PMID- 7505715
TI  - Ruthenium red, ribose, and adenine enhance recovery of reperfused rat heart.
AB  - BACKGROUND: Postischemic cardiac failure may be associated with inadequate
      storage of myocardial adenosine triphosphate (ATP). ATP precursors were
      administered to resuscitate the postischemic myocardium. METHODS: Hearts isolated
      from male Wistar adult rats were perfused with Krebs-Henseleit buffer (pH, 7.40),
      subjected to 30 minutes of global ischemia at 36 degrees C, followed by 30
      minutes of retrograde reperfusion with the postischemic intervention of ruthenium
      red (1 microM), ribose (1 mM), and adenine (1 mM). Multiple analysis of variance
      was used to compare means between groups (eight rats in each group). RESULTS: In
      comparison with the nonischemic group, the postischemic nontreated group had a
      decrease in the maximum rate of left ventricular pressure rise (+dP/dt, P <
      0.0005) and level of myocardial ATP (P < 0.0005) but an increase in level of
      mitochondrial Ca2+ (P < 0.005). In comparison with the nontreated group, ribose
      and adenine had no effect on all the above-mentioned parameters, and ruthenium
      red elevated maximum left ventricular +dP/dt (P < 0.05) and reduced mitochondrial
      Ca2+ (P < 0.05) with no change in ATP (P > 0.05). However, ruthenium red with
      ribose and adenine achieved a significant increase in maximum left ventricular
      +dP/dt (P < 0.0005), ATP levels (P < 0.005), and a decrease in levels of
      mitochondrial Ca2+ (P < 0.005). CONCLUSION: Acute postischemic cardiac failure
      may be related to Ca2+ overload in mitochondria. Ruthenium red may reduce
      mitochondrial Ca2+ overload. Ruthenium red, ribose, and adenine in combination
      may be capable of enhancing the recovery of myocardial high-energy phosphates and
      mechanical function in the postischemic myocardium.

PMID- 7505716
TI  - Reduction of hospital days in chronic schizophrenic patients treated with
      risperidone: a retrospective study.
AB  - Hospital costs for chronic schizophrenic patients consume a major share of the
      cost of mental health care. Despite the success of numerous community mental
      health programs, repeated hospital admission of schizophrenic patients is a
      significant problem. Effective therapy and compliance with that therapy are two
      important factors in reducing hospitalization. Adverse effects of antipsychotic
      agents, particularly extrapyramidal symptoms (EPS), negatively influence
      compliance. A new antipsychotic agent, risperidone, has demonstrated efficacy
      against both positive and negative symptoms of schizophrenia and has been
      associated with a low incidence of EPS. To assess the potential of risperidone
      therapy to reduce the number of days in the hospital, a retrospective analysis
      was undertaken of data from a year-long clinical trial of risperidone. For 27
      patients who had completed 365 days of open-label therapy with risperidone, the
      number of hospital days during this period was compared with the number of
      hospital days in the preceding 365-day period, when the patients were receiving
      conventional antipsychotic medication. The mean number of hospital days was
      reduced from 106 to 85 days, for a 20% reduction (P = 0.003) after the initiation
      of risperidone. Three subgroups of patients were apparent: (1) those who had
      spent no time in the hospital in the pre-risperidone year, (2) those who had been
      continuously hospitalized in the pre-risperidone year, and (3) those who had
      spent part of the pre-risperidone year (3 to 165 days) in the hospital. A 73%
      reduction (P = 0.0009) in mean hospital days (from 49 to 13 days) was achieved in
      the third subgroup (n = 14). These findings suggest that risperidone may have a
      role in reducing hospital days for the chronic schizophrenic population.

PMID- 7505717
TI  - Drug formulary review process for sargramostim and filgrastim: focus on analysis
      of adverse drug reactions.
AB  - Selection of a drug for formulary inclusion involves evaluation of safety,
      efficacy, and cost. The colony-stimulating factors (CSFs) sargramostim and
      filgrastim have a broad range of potential indications and represent a costly
      formulary addition when acquisition price alone is considered; their comparative
      safety is unclear. These factors suggest that the CSFs should be closely
      scrutinized prior to formulary addition. In the absence of direct comparative
      studies, an assessment of the safety of CSFs involves evaluation of information
      provided in the product circular, official drug compendia, adverse biologic
      reports submitted to the United States Food and Drug Administration, and data
      from key clinical trials. Data in the product circulars report on adverse events
      in small numbers of patients treated for chemotherapy-induced neutropenia
      (filgrastim) or neutropenia subsequent to bone marrow transplantation
      (sargramostim). The official compendia and clinical trials include experience
      with CSFs produced in a variety of expression systems; these data are not limited
      to sargramostim and filgrastim. Importantly, there was a similar incidence of
      adverse events in patients who received sargramostim or filgrastim and in those
      who took placebo reported in the product circulars and the pivotal trials,
      suggesting that the underlying disease may have an important role in determining
      the side-effect profile of these agents. Adverse biologic reports represent
      experience with sargramostim and filgrastim obtained under actual clinical
      conditions and suggest that the same types of adverse events are seen with
      sargramostim as with filgrastim. This analysis suggests that a decision to select
      filgrastim over sargramostim for formulary inclusion based on the safety profile
      is not appropriate because currently available data are equivocal and that such
      decisions would more appropriately be based on efficacy and cost.

PMID- 7505718
TI  - Immunohistochemical evidence for the heterogeneity of maternal and fetal vascular
      endothelial cells in human full-term placenta.
AB  - The heterogeneity of endothelial cell surface antigen expression was studied in 5
      human full-term placentae by means of indirect immunohistochemistry using 9
      monoclonal antibodies and by staining with fluorescent-conjugated Ulex europaeus
      lectin, both of which are widely used endothelial cell markers. (1) A highly
      specific, homogeneous staining of fetal and maternal placental vessels of all
      sizes and anatomical regions was observed by the monoclonal antibodies PAL-E,
      QBEND10 and 1F10. These antibodies were even more specific than Ulex europaeus
      lectin, factor VIII antibody and von Willebrand factor antibody, which cross
      reacted with some non-endothelial cells and structures. The reactivity of PAL-E,
      QBEND10 and 1F10 with residual surface cells of the basal plate strongly suggests
      an endothelial origin of these cells. (2) In contrast to other organs, PAL-E,
      QBEND10 and HM15/3 strongly stained endothelial cells of the macrovascular system
      in the human placenta. This might indicate an organ-associated heterogeneity of
      fetal endothelial cells. (3) Monoclonal antibodies against receptors for
      transferrin and IgG (Fc gamma RII) labeled the endothelial cells of fetal
      placental vessels with increasing intensity distal to the insertion of the
      umbilical cord. The vessels of the umbilical cord itself were unreactive. This
      might suggest a heterogeneity of macro- and microvascular endothelial cells.

PMID- 7505719
TI  - Isolation, identification and quantitative evaluation of specific cell types from
      the mammalian gastric mucosa.
AB  - Functional in vitro studies with isolated gastric mucosal cells require
      cytological identification of different cell types in suspension or primary
      culture. Since suitable techniques have not been well established, different
      staining methods for the discrimination of dispersed pig and guinea pig gastric
      cells have been developed on the basis of modified previous protocols for
      enzymatic cell dispersion. Chief and parietal cells were visualized by combined
      periodic acid-Schiff stains. Surface mucous and mucous neck cells were identified
      by affinity-labelling, using lectins with selective staining properties in situ.
      Two of the lectins were found to be specific markers for gastric
      polymorphonuclear cells. The following vital tests were found to be useful:
      succinic dehydrogenase for parietal cells, Nile blue/brilliant cresyl blue stains
      for chief cells, and different phagocytosis assays for endothelial cells and
      gastric phagocytes. Endocrine cells were characterized by immunocytochemistry
      using specific antibodies against gastrin, somatostatin, histamine and serotonin.
      The same technique using a vimentin antibody was performed for the identification
      of fibroblasts. Proliferation of mucosal cells in primary culture was monitored
      by the incorporation of bromo-deoxyuridine, which was subsequently detected by a
      monoclonal antibody.

PMID- 7505721
TI  - Targeted disruption of the neuronal nitric oxide synthase gene.
AB  - By homologous recombination, we have generated mice that lack the neuronal nitric
      oxide synthase (NOS) gene. Neuronal NOS expression and NADPH-diaphorase (NDP)
      staining are absent in the mutant mice. Very low level residual catalytic
      activity suggests that other enzymes in the brain may generate nitric oxide. The
      neurons normally expressing NOS appear intact, and the mutant NOS mice are
      viable, fertile, and without evident histopathological abnormalities in the
      central nervous system. The most evident effect of disrupting the neuronal NOS
      gene is the development of grossly enlarged stomachs, with hypertrophy of the
      pyloric sphincter and the circular muscle layer. This phenotype resembles the
      human disorder infantile pyloric stenosis, in which gastric outlet obstruction is
      associated with the lack of NDP neurons in the pylorus.

PMID- 7505720
TI  - Ultrastructure of free nerve endings in respiratory and squamous epithelium on
      the rat nasal septum.
AB  - The distribution of nerve fibres in the mucosa of the nasal septum of the rat was
      investigated by means of transmission electron microscopy on transverse and
      tangential ultrathin sections. Near the basement membrane of respiratory and
      squamous epithelium, a rather dense network of unmyelinated nerve fibres occurs.
      Some fibres in the respiratory epithelium ascend between the epithelial cells to
      reach up to the tight junctions. These fibres appeared in transverse sections to
      end as hooks or boutons, sometimes with branches. These shapes resemble the free
      nerve endings that are considered to act as nociceptors. The small
      intraepithelial fibres, with diameters of about 0.5-1 microns, contain both dense
      granules and clear vesicles comparable to synaptic vesicles. Substance P was
      found in dense granules in basal fibres; vasoactive intestinal peptide was absent
      throughout the epithelium. Acetylcholinesterase activity was observed closely
      associated with the basal fibres; the apical fibres showed little if any
      activity. Membrane specializations pointing to an efferent function as well as
      structures usually associated with mechanoreceptive functions were lacking in
      both respiratory and squamous epithelium.

PMID- 7505722
TI  - Steady-state plasma concentrations and effects of taxol for a 250 mg/m2 dose in
      combination with granulocyte-colony stimulating factor in patients with ovarian
      cancer.
AB  - Taxol, a natural product initially isolated from the stem bark of the western yew
      Taxus brevifolia, is undergoing phase II and III evaluation due to its reported
      activity against a variety of tumors. Previous studies have described
      correlations between plasma concentrations and toxicity when taxol is given (a)
      at lower doses, (b) for shorter infusion times, and (c) without granulocyte
      colony-stimulating factor. Because the 24-h infusion schedule is most commonly
      used in current clinical trials, we attempted to correlate steady-state plasma
      concentrations of taxol achieved with a 24-h continuous i.v. infusion with
      toxicities and responses. Plasma samples from 48 refractory ovarian cancer
      patients were obtained 1-2 h prior to the end of the first taxol infusion. Taxol
      concentrations were measured by high-performance liquid chromatography (HPLC).
      Interpatient variation of taxol plasma concentrations was small (mean +/- SD,
      0.85 +/- 0.21 microM. Total taxol body clearance was 256 +/- 72 ml min-1 m-2
      (mean +/- SD). Taxol plasma protein binding was 88.4% +/- 1.3% (mean +/- SD, n =
      9). Grade 3-4 hematologic toxicity, mainly leukopenia, occurred in 92% of the
      patients. The leukopenia was transient and did not warrant a reduction in the
      dose of taxol. Grade 3-4 nonhematologic toxicity occurred in 8% of the patients.
      No severe hypersensitivity reaction or grade 3-4 neurotoxicity was observed.
      Correlations of plasma concentrations and toxicities were not feasible due to the
      high frequency of hematologic effects and the low frequency of nonhematologic
      toxicity. The low degree of interpatient variation in plasma concentrations
      hindered the development of correlations with response.

PMID- 7505724
TI  - Poly-D-lysine enhances the genotoxicity of bleomycin in cultured CHO cells.
AB  - Cultured CHO cells were treated with the radiomimetic antitumor agent bleomycin
      (BLM) and post-treated with the polycationic compound poly-D-lysine (PDL),
      recently reported by us as able to potentiate chromosome damage induced by X-rays
      and chemical mutagens in both plant and mammalian cells. Our results seem to
      indicate that PDL enhances the genotoxic action of BLM measured as induced
      chromosomal aberrations, colony-forming ability and DNA strand breakage. Taking
      into account the reported low efficiency of BLM treatment due to problems with
      cellular uptake, enzymatic degradation and efficient repair, the possibility of
      optimizing the dose-effectiveness for cancer therapy is discussed.

PMID- 7505723
TI  - Isolation and characterization of a mitomycin C-resistant variant of human colon
      carcinoma HT-29 cells.
AB  - To investigate the resistant mechanisms against MMC in human tumor cells, we
      isolated an MMC-resistant variant (HT-29/MMC) of HT-29 human colon carcinoma
      cells. HT-29/MMC cells showed 5-fold resistance to MMC as compared with the
      parental cell line but did not show cross-resistance to Adriamycin, vincristine,
      ACNU, bleomycin, or cisplatin. Treatment of the cells with dicoumarol, an
      inhibitor of DT-diaphorase, reduced the cytotoxicity of MMC in DT-diaphorase
      proficient HT-29 cells but not in HT-29/MMC cells. HT-29/MMC cells were 5 times
      more sensitive than HT-29 cells to menadione, which is detoxified by DT
      diaphorase, DT-diaphorase was deficient in HT-29/MMC cells as determined by the
      enzyme activity and immunoblot analysis of the cytoplasmic proteins. Levels of
      cytochrome P-450 reductase and glutathione S-transferase, however, were
      comparable in both cell lines. The amount of [3H]-MMC found covalently bound to
      chromosomal DNA in HT-29/MMC cells was one-fourth that detected in HT-29 cells.
      Treatment with dicoumarol reduced the DNA-bound MMC in HT-29 cells but not in HT
      29/MMC cells. These results indicate that the deficiency in DT-diaphorase, an
      activating enzyme of MMC, is one of the mechanisms of resistance in HT-29/MMC
      cells.

PMID- 7505725
TI  - Involvement of proliferating cell nuclear antigen in DNA repair after damage
      induced by genotoxic agents in human fibroblasts.
AB  - The association of the proliferating cell nuclear antigen (PCNA) to DNA synthesis
      sites during the process of DNA repair, was investigated in human diploid
      fibroblasts after treatment with different genotoxic agents. For this purpose,
      confluent cultures were treated with agents that form primarily DNA adducts, such
      as u.v.-C, 8-methoxypsoralen (8-MOP) and 4,4',6-trimethylangelicin (TMA), or with
      agents that induce strand breaks, such as X-rays or bleomycin (BLM). Chromatin
      associated PCNA was detected with a monoclonal antibody and indirect
      immunofluorescence labelling. Quantitative analysis was performed by flow
      cytometry. Not all of the tested agents were able to activate the association of
      PCNA with chromatin. X-rays, u.v.-C and BLM induced a significant increase in
      PCNA complex as compared to the control samples. In contrast, 8-MOP and TMA did
      not show any detectable effect on the levels of associated PCNA, even at post
      incubation repair times as long as 10 h. However, these drugs damaged DNA, as
      shown by the formation of micronucleated cells 48 h after treatment. The lack of
      PCNA activation was not due to an inhibition of the repair mechanism, since in
      TMA-treated fibroblasts, subsequent irradiation with u.v.-C induced an increase
      in PCNA levels comparable to that found in cells treated with u.v.-C alone. These
      results indicate that PCNA is involved in DNA excision repair of genotoxic
      agents, but suggest that similar types of lesions may be repaired with
      alternative pathways not requiring PCNA.

PMID- 7505726
TI  - Lipopolysaccharide induces interleukin-6 release from rat peritoneal macrophages
      in vitro: evidence for a novel mechanism.
AB  - Interleukin-6 (IL-6) is a cytokine involved in the terminal differentiation of B
      cells, T-cell activation, and secretion of hepatic acute phase proteins. The
      production of IL-6 is regulated by many factors, including IL-1 and
      lipopolysaccharide (LPS). Because IL-6 may be an important contributor to the
      effects of LPS in inflammation and septic shock, we investigated the ability of
      LPS to induce IL-6 release from peritoneal macrophages (m phi) in vitro. M phi
      were isolated from male Long-Evans rats, and cultured in 96-well tissue culture
      plates at 1 x 10(5) cells/well in serum-free RPMI-1640 medium. Following a 2-hr
      attachment period, the cells were rinsed twice to remove the nonadherent cells.
      LPS (0.006-100 ng/ml) stimulated IL-6 release by six- to 12-fold during a 4 hr
      incubation. In contrast, IL-1 beta (0.006-100 ng/ml) had no effect. Because
      cyclooxygenase metabolites of arachidonic acid are increased by LPS, we
      determined the effects of indomethacin (a cyclooxygenase inhibitor) and CGS8515
      (a 5-lipoxygenase inhibitor) on LPS-induced IL-6 release. Neither indomethacin
      (10 microM) nor CGS8515 (2.5 microM) had any effect on basal or LPS-induced IL-6
      release. Very low concentrations of LPS (0.01-1,000 pg/ml) stimulated IL-6 by two
      to threefold. Pertussis toxin (10 ng/ml), which inactivates Gi protein, had no
      effect on LPS-induced IL-6 release from mo. Thromboxane B2 (TXB2) concentrations
      were also elevated with as little as 0.1 pg/ml LPS; however, pertussis toxin
      inhibited LPS-stimulated TXB2 release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505727
TI  - Fluid shifts induced by the administration of 7.5% sodium chloride in 6% dextran
      70 (HSD) in dehydrated swine.
AB  - This study determined the effects of HSD administration on fluid distribution,
      following dehydration in Female Yucatan micro pigs. Dehydration at 33 degrees C
      resulted in: significantly increased core temperature (37.2 +/- 0.2 (mean +/- SE)
      to 39.0 +/- 0.1 degrees C), and decreased (4.4 +/- 0.4%) body weight and plasma
      volume (PV, 43 +/- 2 to 37 +/- 1 ml/kg). HSD but not saline administration
      resulted in significant increases (over postdehydration levels) in PV (46 +/- 3
      ml/kg), sodium concentration (141 +/- 1 to 150 +/- 2 mEq/L), and osmolality (291
      +/- 2 to 307 +/- 11 mOsm). Following return of water to the animals, these values
      returned to baseline levels. Since insensible (respiratory and transdermal) water
      loss for the 24 hr at 23 degrees C was 714 +/- 64 ml, and for the 24 hr at 33
      degrees C was 653 +/- 64 ml, increasing the ambient temperature did not result in
      increased dehydration in swine. HSD administration restored PV to baseline levels
      despite prior water loss dehydration.

PMID- 7505728
TI  - Changes in the hepatic oxygenation state during hemorrhage and following
      epinephrine or dextran infusion as assessed by near-infrared spectroscopy.
AB  - Changes in the hepatic oxygenation state of rabbits during hemorrhage and
      subsequent epinephrine (n = 6) or dextran infusion (n = 6) were assessed by
      tissue near-infrared spectroscopy. Oxygen saturation of hemoglobin in the liver
      (hepatic SO2), and redox transition of cytochrome aa3 were analyzed by applying
      multicomponent analysis to the absorption spectrum of the liver. Hepatic SO2,
      representing extracellular oxygenation state, decreased from 62.4 +/- 2.7% (mean
      +/- SEM) to 21.1 +/- 7.3% after bleeding. It increased to 31.8 +/- 6.6% after
      epinephrine infusion, but returned to near-control levels after dextran infusion.
      Intracellular oxygenation state as assessed by the changes in the oxidized and
      reduced forms of cytochrome aa3 was impaired after bleeding, and remained as such
      even after epinephrine infusion. By contrast, it was normalized to near control
      levels after dextran infusion. Changes in the difference of hepatic SO2 and
      hepatic venous SO2 suggested that the intrahepatic blood flow was more
      heterogeneously distributed after bleeding, but that the heterogeneity of
      microcirculation was rather diminished after epinephrine infusion.

PMID- 7505729
TI  - Cholecystokinin modulates isoproterenol induced changes in rat parotid gland.
AB  - 1. Parotid gland secretory function and activity of several enzymes involved in
      intracellular second messenger signalling were measured in rats receiving 0.5 ml
      i.p. injections of saline (control), isoproterenol, CCK or both drugs. 2.
      Isoproterenol caused a 2.5-fold increase in parotid gland wet weight compared to
      control. Chronic administration of CCK alone has no effect on gland weight. A
      combination of CCK and isoproterenol did not alter the hypertrophy of the gland
      observed with isoproterenol alone. 3. Isoproterenol administration caused a 74%
      decrease in parotid gland amylase enzyme activity. While CCK alone did not
      influence the enzyme activity, it depressed amylase mRNA steady state levels and
      had an additive effect on further decreasing mRNA levels when administered in
      combination with beta-agonist. 4. Phospholipase C registered an increase ranging
      from 22 to 38% in all experimental groups as compared to control. 5. Parotid
      gland protein kinase C and PdtIns 3-kinase activity were not altered in response
      to CCK alone, but in combination with isoproterenol, appeared to moderate beta
      agonist signal transduction responses.

PMID- 7505730
TI  - Interactions of elastin and microfibrils in elastogenesis of human pulmonary
      fibroblasts in culture.
AB  - The interaction of elastin and microfibrils in elastogenesis in vitro was
      investigated with electron microscopy and immunohistochemistry. Fetal human
      pulmonary fibroblasts were cultured with or without beta-aminopropionitrile
      (BAPN). One week after seeding, the extracellular microfibrils were loosely
      arranged without elastin deposition. Two and six week culture in controls, mature
      elastic fibers and microfibril bundles were formed. In cultures with BAPN, the
      microfibrils were loosely arranged, and a few microfibril bundles and no
      amorphous components were formed. Immunoelectron microscopy for elastin showed
      the reaction at the outer zones of amorphous components in controls, though the
      loosely-arranged microfibrils reacted diffusely in cultures with BAPN. Six week
      culture with BAPN, aggregated masses of elastin, which were dissociated from
      microfibrils, were found. In conclusion, deposition and maturation of elastin on
      microfibrils are necessary to form the microfibril bundles in normal
      elastogenesis, and vaguely outlined aggregated masses of elastin are formed under
      the inhibition of lysyl oxidase.

PMID- 7505731
TI  - [Interventions on the urogenital tract within the scope of oncologic surgery].

PMID- 7505732
TI  - [The role of arginine-vasopressin and substance P in the pathogenesis of
      hypertension and their interrelation].
AB  - In this study, the concentration of plasma arginine vasopressin (AVP) and
      substance P (SP) in normotensive subjects as well as patients with essential
      hypertension was measured. The results showed that: (1) The concentration of
      plasma AVP in patients with essential hypertension (21.83 +/- 1.30ng/L) was
      significantly higher than that in normotensive subjects (11.02 +/- 1.05 ng/L) (P
      < 0.001). The level of plasma SP in hypertensive subjects (276.60 +/- 21.35
      pmol/L) was obviously lower than that in normotensive subjects (958.20 +/- 31.13
      pmol/L) (P < 0.001). (2) The level of plasma AVP decreased (from 24.88 +/- 1.63
      to 8.69 +/- 1.39 ng/L, P < 0.001) and that of plasma SP increased (from 331.40 +/
      48.18 to 958.80 +/- 39.30 pmol/L, P < 0.001) after antihypertensive drug
      treatment. (3) A negative correlation was found between the level of plasma AVP
      and SP in patients with essential hypertension (r = -0.564, P < 0.001), but no
      correlation was found between them in normotensive subjects (r = -0.096, P >
      0.05). It is suggested that the abnormal level of plasma AVP and SP plays a role
      in the pathogenesis of hypertension.

PMID- 7505733
TI  - [Current status in the research of B-mode ultrasonographic diagnosis of small
      primary liver cancer].

PMID- 7505734
TI  - [Small molecule ribonuclear components and ribonucleoprotein complex antigens and
      rheumatic diseases].

PMID- 7505735
TI  - Intraperitoneal insulin affects insulin-like growth factor binding protein-1 in a
      well-controlled type I diabetic patient.

PMID- 7505736
TI  - The impact of a color-classified HbA1c graph for self-monitoring and self
      adjustment of long-term glycemic control.

PMID- 7505738
TI  - Stem cell factor and leukemia inhibitory factor promote primordial germ cell
      survival by suppressing programmed cell death (apoptosis).
AB  - Proliferating primordial germ cells (PGCs) isolated from mouse embryos soon after
      their arrival in the genital ridges would only survive in vitro at temperature of
      less than 30 degrees C (De Felici, M. and McLaren, A. (1983). Exp. Cell. Res.
      144, 417-427; Wabik-Sliz, B. and McLaren, A. (1984). Exp. Cell. Res. 154, 530
      536) or when co-cultured on cell feeder layers (Donovan, P. J., Stott, D., Godin,
      I., Heasman, J. and Wylie, C. C. (1986). Cell 44, 831-838; De Felici, M. and
      Dolci, S. (1991). Dev. Biol. 147, 281-284). In the present paper we report that
      mouse PGC death in vitro occurs with all the hallmarks of programmed cell death
      or apoptosis. We found that after 4-5 hours in culture many PGCs isolated from
      12.5 dpc fetal gonads assumed a nuclear morphology and produced membrane bound
      fragments (apoptotic bodies) typical of apoptotic cells. In addition, PGCs in
      culture accumulated high level of tissue transglutaminase (tTGase; an enzyme that
      is induced and activated during apoptosis) and showed extensive degradation of
      DNA to oligonucleosomal fragments, which is characteristic of apoptosis. The
      physiological relevance of this mechanism of PGC death is supported by the
      finding that some PGCs undergoing apoptosis, as revealed by the high level of
      tTGase expression, were detected in the embryo. Most importantly, we show that
      the addition of stem cell factor (SCF) or leukemia inhibitory factor (LIF) to the
      culture medium, two cytokines known to favour PGC survival and/or proliferation
      in vitro, markedly reduced the occurrence of apoptosis in PGCs during the first
      hours in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505737
TI  - Iloprost decreases urinary albumin excretion rate in patients with diabetic
      nephropathy.
AB  - We conducted an open clinical trial to determine whether administration of
      iloprost, a stable prostacyclin analog, has any effect on urinary albumin
      excretion and other parameters associated with non-insulin-dependent diabetes
      mellitus (NIDDM) patients. Twenty-three NIDDM patients with nephropathy were
      divided into groups A and B which were matched in terms of sex, age, duration of
      diabetes and blood glucose control. After 2 weeks of observation, 11 patients in
      group A received an intravenous infusion of iloprost (10 micrograms at a rate of
      0.075 microgram/kg per h) once daily for 2 weeks, while 12 untreated diabetic
      patients in group B served as controls. In group A, iloprost significantly
      reduced the urinary albumin excretion rate, the urinary albumin-creatinine ratio
      and N-acetyl-beta-D-glucosaminidase without decreasing creatinine clearance
      during the treatment period (P < 0.05, respectively). However, none of these
      parameters changed significantly in group B. Urinary beta 2-microglobulin, blood
      pressure, heart rate, serum electrolytes, BUN and serum creatinine were not
      significantly altered by iloprost during the treatment period. Side effects
      associated with iloprost were mild and could be ameliorated by slowing the
      infusion rate. We conclude that iloprost appears to be safe and has an apparent
      effect on the urinary albumin excretion rate and N-acetyl-beta-D-glucosaminidase.

PMID- 7505739
TI  - Neuromelanin accumulation with age in catecholaminergic neurons from Macaca
      fascicularis brainstem.
AB  - Neuromelanin (NM) is an auto-oxidation by-product of catecholamine synthesis
      which is observed almost exclusively in primates. We have estimated the
      distribution and the number of NM-positive neurons of the upper brainstem and the
      degree of their melanization from birth to the onset of senescence in 5 monkeys
      (Macaca fascicularis) aged 0, 1.5, 3.5, 8 and 13 years. Series of sections taken
      at 640-microns intervals were examined either unstained to detect unstained NM,
      stained for NM with Masson silver impregnation or processed by tyrosine
      hydroxylase (TH) immunohistochemistry to analyze catecholaminergic neurons. The
      proportion of NM-containing cells among TH-positive neurons varied from one
      catecholaminergic region to another: low in the hypothalamus and central gray
      substance (cgs); moderate in the cell group A8, and high in the ventral tegmental
      area (VTA), locus coeruleus (LC) and substantia nigra (SN). TH-positive neurons
      were detected in the SN, VTA, catecholaminergic cell group A8, LC, cgs and
      hypothalamus. At birth, although no unstained NM-positive neurons were detected,
      Masson-stained cells were observed, though only in the LC. At 1.5 and 3.5 years,
      Masson-positive neurons were observed despite the absence of visible pigment. At
      8 and 13 years, unstained NM was present in Masson-positive neurons. The number
      of unstained NM-positive neurons and Masson-positive neurons and the amount of NM
      per neuron increased with age in each subregion studied. Nevertheless, some TH
      positive neurons were found to be without NM. The data indicate a differential
      increased NM content with age in the neurons of midbrain catecholaminergic cell
      groups. However, its functional significance remains to be determined.

PMID- 7505740
TI  - Investigation of the changes in neuronal distribution and phosphorylation state
      of MAP1X during development.
AB  - Neurite outgrowth is dependent on the presence in neurites of assembled
      microtubules which consist of polymerized tubulin to which microtubule-associated
      proteins (MAPs) are bound. This study adds to previous evidence of the similarity
      between the high molecular weight MAPs, MAP1X, MAP1B and MAP5, and explains the
      different staining patterns observed by different laboratories on frozen
      sections, using monoclonal antibodies against each MAP. Previous studies have
      shown that monoclonal antibody (mAb) G10 binds to MAP1X and labels growing but
      not mature axons in the rat nervous system and, therefore, expression of this MAP
      or molecular changes in it may be important for axon growth. It has been shown
      that a phosphorylated form of MAP5 can be detected by SDS-PAGE in brain areas
      with growing axons. This study shows that there is phosphate dependency of mAbG10
      binding to MAP1X which is, however, lost during brain homogenization.

PMID- 7505741
TI  - The role of dietary polyamines.

PMID- 7505743
TI  - Gene targeting in human somatic cells. Complete inactivation of an interferon
      inducible gene.
AB  - The role, if any, of the human interferon-inducible 6-16 gene in the
      establishment of a cellular antiviral state is unknown. To address this problem,
      and as part of a wider investigation of homologous recombination (HR) and its
      applications in somatic cells, we have been using HR to disrupt the 6-16 gene in
      human cell lines [Itzhaki, J. E. & Porter, A. C. G. (1991) Nucleic Acids Res. 19,
      3835-3842.] We describe here the design and use of insertion and replacement-type
      targeting constructs based on a promoterless bacterial gpt gene that is activated
      by HR with the 6-16 gene. In HeLa cells, both targeting constructs underwent
      extrachromosomal HR with a cotransfected plasmid carrying the 6-16 gene. In a
      previously targeted clone derived from the fibrosarcoma cell line HT1080, the
      replacement construct underwent HR with either the modified or the unmodified 6
      16 allele. The latter events generated doubly disrupted (6-16-/-) clones that
      failed to express any detectable 6-16 messenger RNA in response to interferon.
      Plaque assays of infected 6-16-/- cells showed that expression of the 6-16 gene
      was not required for the induction by interferon of an antiviral state against
      encephalomyocarditis virus, semliki forest virus or cocal virus.

PMID- 7505742
TI  - Gabapentin actions on ligand- and voltage-gated responses in cultured rodent
      neurons.
AB  - Gabapentin (GBP) is a cyclic gamma-aminobutyric acid (GABA) analog and
      investigational antiepileptic drug which is effective in the treatment of a
      variety of human and experimental seizures. GBP's antiepileptic mechanism of
      action is not known. The present studies tested for effects of GBP on inhibitory
      (GABA and glycine) and excitatory (N-methyl-D-aspartate (NMDA) and non-NMDA)
      amino acid neurotransmitter receptors, on repetitive firing of sodium (Na+)
      action potentials, and on voltage-dependent calcium (Ca2+) channel currents in
      cultured rodent neurons using intracellular, whole cell, or single channel
      recording techniques. GBP did not have a significant effect in any experiment
      when tested at or above concentrations that are therapeutic in humans except for
      a variable enhancement of NMDA-evoked depolarizations. These results suggest that
      the antiepileptic activity of GBP is not due to direct effects at receptors for
      inhibitory or excitatory amino acids or on voltage-dependent Na+ or Ca2+
      channels.

PMID- 7505744
TI  - Isolation and characterization of the human inter-alpha-trypsin inhibitor heavy
      chain H1 gene.
AB  - The human inter-alpha-trypsin inhibitor heavy chain H1 (ITI heavy chain H1) gene
      was isolated from two overlapping clones. It spans 14 kbp and is composed of 22
      exons from 15 bp to 281 bp in size and has consensus splice sites. Intron sizes
      range from 80 bp to 2000 bp. It codes for the precursor of HC1 that is part of
      the serum ITI form of 220 kDa. Two major transcriptional initiation sites were
      identified in the 5'-flanking region, which contained putative promoter elements,
      but no typical TATA and CAAT boxes. mRNA for the ITI heavy chain H1 was found
      only in liver. The tissue-specific transcription of the gene might be due to the
      presence of binding sites for the hepatocyte nuclear factor HNF-5 and to the
      octameric motifs. A previous overlapping of cDNA clones indicated the absence of
      29 bp in one of these clones. The present study shows that the 29 bp is located
      within the gene at the end of exon 21. A reverse-transcriptase polymerase chain
      reaction mapping analysis of liver mRNA identified the two types of the mRNA for
      ITI heavy chain H1. Accordingly, the data demonstrate that there is alternative
      splicing of at least one exon of the ITI heavy chain H1 gene.

PMID- 7505745
TI  - NAD turnover and utilisation of metabolites for RNA synthesis in a reaction
      sensing the redox state of the cytochrome b6f complex in isolated chloroplasts.
AB  - NAD is normally regarded as a redox molecule or as the substrate for ADP
      ribosylation reactions. In this study, we describe the rapid metabolism of NAD by
      Percoll-gradient-purified lettuce chloroplasts and show that the adenine moiety
      can be incorporated into RNA in a dark-activated reaction that senses the redox
      state of the cytochrome b6f complex. Isolated chloroplasts rapidly metabolised
      radiolabelled NAD+ to 5'-AMP (within seconds) and adenosine during a 60-min
      incubation in vitro; the products were analysed by high-performance liquid
      chromatography. No radiolabelled ADP-ribose was detected. Radioactivity was
      incorporated into trichloroacetic-acid-insoluble material during this period,
      with approximately 2-4-fold more incorporation occurring in the dark. Most of
      this radiolabel was rendered acid-soluble by dilute alkaline digestion at 37
      degrees C, yielding an approximately equal mixture of 2'-AMP and 3'-AMP, and by
      RNase digestion, identifying the acid-insoluble radioactive material as RNA.
      Protein-bound ADP-ribose would have yielded 5'-AMP and/or oligomeric/polymeric
      ADP-ribose after alkali digestion. The utilisation of NAD metabolites for RNA
      synthesis was restricted to the thylakoid compartment of the chloroplast. The use
      of a variety of electron-transport inhibitors such as 2,5-dibromo-3-methyl-6
      isopropyl-p-benzoquinone, bromanil (tetrabromo-1,4-benzoquinone), electron donors
      (dithiothreitol), electron acceptors (ferricyanide) and an uncoupler showed that
      the incorporation of radiolabel from NAD into acid-insoluble material was
      favoured when the cytochrome b6f complex was in the oxidised state (as pertaining
      to incubations in the dark).

PMID- 7505746
TI  - Expression of beta 1, beta 3, beta 4, and beta 5 integrins by human lung
      carcinoma cells of different histotypes.
AB  - Structural and functional analyses of several integrin heterodimers were
      performed in non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC)
      cell lines. The expression of beta 1, beta 3, beta 4, and beta 5 heterodimers was
      evaluated at protein and mRNA levels. By flow cytometry and immunoprecipitation
      experiments we demonstrate that NSCLC cells (A549 adenocarcinoma and DG 3 large
      cell carcinoma) coexpress integrin heterodimers composed of beta 1, beta 3, beta
      4, and beta 5 subunits, whereas SCLC cells (AE2 and H69) express only beta 1
      integrin heterodimers. Northern blot experiments confirmed immunochemical
      analysis: SCLC cells in contrast to NSCLC cells express only the mRNA coding for
      the beta 1 subunit. These data indicate that in lung carcinoma cells the
      diversity in the integrin repertoire depends upon differential gene expression.
      The functionality of integrin receptors has been studied using antibody blocking
      experiments. Data reported demonstrate that the alpha 6 beta 1 integrin is a
      laminin receptor in either SCLC or NSCLC cells. An antibody to the beta 4 subunit
      partially inhibits the adhesion of adenocarcinoma cells to lamin but does not
      block lamin adhesion of large cell carcinoma cells, even though alpha 6 beta 4
      complexes are expressed on both cell types. Two antisera to vitronectin receptors
      inhibit the adhesion of NSCLC cels to both vitronectin and fibronectin. The same
      antisera inhibit the adhesion of SCLC cells only to laminin, indicating that the
      alpha v beta 1 integrin might function in these cells as laminin receptor.

PMID- 7505747
TI  - Heat shock-induced shedding of cell surface integrins in A549 human lung tumor
      cells in culture.
AB  - The human lung carcinoma-derived cell line A549 attaches to plastic and
      vitronectin-coated substrates in a manner dependent upon the specific cell
      surface integrin alpha v beta 3. Exposure to hyperthermic temperatures (42-45
      degrees C) causes these cells to detach from the substrates. In heat-shocked
      cultures, the alpha v, alpha 5, and beta 3 integrin subunits remain attached to
      the substrate. Analysis of individual cells by fluorescence-activated cell
      sorting shows that cell surface levels of alpha v beta 3 decrease by up to 10
      fold in response to heat shock, while the abundance of another integrin found on
      the surface of A549 cells, alpha 3 beta 1, is only minimally affected by this
      stress. Heat shock-induced decreases in alpha v beta 3 also occur in cells
      growing in suspension cultures, showing that physical attachment onto an
      extracellular substrate is not required for the hyperthermia-induced loss of this
      integrin. The heat shock-induced detachment of the cells and the shedding of
      alpha v beta 3 from the cell surface can be inhibited by fetal bovine serum and
      alpha 2 macroglobulin. Reattachment of A549 cells to substrate is reduced by heat
      shock. These results demonstrate that heat shock can reduce the cell surface
      abundance of specific integrin subunits, some of which are involved at sites of
      cellular attachment to extracellular substrates. These findings may be relevant
      to the heterogeneous patterns of invasion and metastasis of human tumors
      following fevers or hyperthermia therapy.

PMID- 7505748
TI  - Molecular subtyping by genome and plasmid analysis of Campylobacter jejuni
      serogroups O1 and O2 (Penner) from sporadic and outbreak cases of human
      diarrhoea.
AB  - Ribosomal RNA gene patterns, randomly amplified polymorphic genomic DNA (RAPD)
      profiles and plasmid profiles were used to discriminate between 28 strains of
      Campylobacter jejuni serogroups O1 and O2 (Penner). Most isolates were biotype I
      (Lior). The strains were representative isolates from a UK school outbreak of
      enteritis (7 cases) and from 21 sporadic human cases of enteritis in 4 countries.
      The molecular techniques discriminated to various degrees between strains in each
      of the serogroups. The outbreak strains were homogeneous in most molecular
      features but a variety of types was detected amongst the isolates from the
      sporadic cases. Five groups of two or more strains with identical ribopatterns
      were identified and within each, strains from different patients were homogenous
      with respect to serogroup. RAPD profile typing based on numerical analysis
      generally matched ribotyping. Plasmid profiling overall gave least discrimination
      but was useful in separating some strains similar in other features. We concluded
      that optimal discrimination of C. jejuni could best be achieved using a
      combination of phenotypic and genotypic properties. Hae III ribotyping was the
      single most discriminatory and reproducible technique investigated. Several
      strains of C. jejuni from sporadic infections had similar molecular profiles
      which have potential for general typing purposes.

PMID- 7505749
TI  - Individual corticorubral neurons project bilaterally during postnatal development
      and following early contralateral cortical lesions.
AB  - The corticorubral projections in adult cats are primarily uncrossed. However,
      early in development and after early unilateral lesions of the sensorimotor
      cortex, crossed corticorubral projections are also observed. The present study
      was performed to disclose (1) whether the crossed projections originate from
      neuronal subpopulations different from those producing uncrossed ones and (2) how
      the neurons that give rise to the crossed projections in the lesioned animals are
      related to those occurring in normal development. We injected fluorescent latex
      microspheres into the red nucleus of two groups of animals: (1) intact kittens at
      postnatal week 3 and (2) kittens that had received unilateral ablation of the
      cerebral cortex at this stage and were then allowed to survive for at least 4
      weeks. Red fluorescing microspheres were injected on one side and green ones on
      the other. In both normal and lesioned kittens, a number of cells in the cortex
      were labeled as a result of the contralateral as well as the ipsilateral
      injections, and no difference in size or distribution was found between the cells
      labeled from contralateral and ipsilateral injections. More than half of the
      cells labeled from contralateral injections were double-labeled in both groups of
      animals. These results indicate that individual corticorubral cells project
      bilaterally in normal development as well as following unilateral lesions of the
      cortex. With respect to the cells producing crossed projections, they were
      similar in both laminar and regional distributions between the intact and
      lesioned animal, suggesting that the crossed projections arise from the same
      neuronal subpopulation before and after cortical lesions. This view was supported
      by sequential injections of the tracers, which indicated that cells normally
      projecting contralaterally maintained the crossed projection after the lesions.
      Taking into account our previous observations that growth and proliferation of
      crossed corticorubral axons took place in the red nucleus (Murakami et al.
      1991a), it is likely that growth and proliferation of the axons in denervated
      targets play a major role in lesion-induced establishment of aberrant
      projections.

PMID- 7505751
TI  - The effects of intraoperative vasodilators and angiographic contrast medium on
      the endothelium and smooth muscle cells of vein grafts.
AB  - Cellular injury is a major cause of intimal hyperplasia in vein grafts. The
      effects of exposure of vein samples to iopamidol, papaverine and iloprost were
      studied in vitro in an organ chamber to determine whether these agents cause
      endothelial and/or smooth muscle cell injury. Smooth muscle cell function was
      assessed by eliciting a dose response curve to noradrenaline. Endothelial cell
      function was assessed by measuring the degree of endothelial-dependent relaxation
      of sub-maximally contracted vein samples. Iopamidol and iloprost did not have any
      deleterious effect on endothelial or smooth muscle cell function. Papaverine did
      not affect endothelial-dependent relaxation but did produce a significant
      decrease in smooth muscle contraction. The use of these intraoperative agents
      during femorodistal bypass does not appear to cause functional injury to the
      endothelial or smooth muscle cells.

PMID- 7505750
TI  - Calcitonin gene-related peptide-like immunoreactivity in motoneuron pools
      innervating different hind limb muscles in the rat.
AB  - The content of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in
      motoneurons was studied in four motor pools supplying muscles in the rat hind
      limb subserving different types of motor activity. The motor pools were
      identified by retrograde labeling with horseradish peroxidase or fluorophore
      conjugated dextran amines, which were injected into the soleus, tibialis
      anterior, lateral gastrocnemius, or abductor digiti minimi muscles. After
      processing for immunohistochemistry, a semiquantitative evaluation was carried
      out to estimate the proportion of strongly, intermediately, and weakly labeled
      motoneurons, as well as motoneurons totally lacking CGRP staining. This revealed
      a considerable diversity in the intensity of CGRP labeling even for motoneurons
      in the same motoneuron pool. Thus, strongly labeled cells, as well as cells
      devoid of CGRP label, were found in all four motoneuron pools. However, a
      difference was found in the distribution of motoneurons innervating muscles with
      a dominant composition of fast and slow motor units, respectively, in that a
      larger fraction of the latter type lacked CGRP-LI. Moreover, generally
      motoneurons in the small motor units of the abductor digiti minimi muscle
      displayed weaker staining, and a larger proportion of cells was totally devoid of
      CGRP-LI (16%) compared with larger motor units of the other three muscles (1
      10%). Small-sized cells within the gamma-motoneuron size range were weakly
      stained or, more frequently, totally devoid of CGRP label (50%) as compared to
      larger cells, presumably representing alpha-motoneurons (1-16%). Five days after
      axotomy all four studied motoneuron pools displayed stronger CGRP labeling than
      corresponding unlesioned pools. However, a considerable variation in CGRP
      labeling persisted also among axotomized motoneurons. These results indicate that
      motoneurons normally display a great variation in CGRP-LI levels, but that
      motoneurons of small and slow-twitch motor units in general have lower levels
      than motoneurons of large and fast-twitch motor units, respectively. After
      axotomy, CGRP-LI increases in lesioned motoneuron pools compared with normal, but
      in a fraction of the axotomized motoneurons the increase seems to be discrete or
      even absent. The possible physiological implications of these findings are
      discussed.

PMID- 7505752
TI  - The effect of iloprost in patients with rest pain.
AB  - Thirty-four patients with ischaemic rest pain in 42 limbs and ankle pressure
      equal to or less than 50 mmHg have been treated with intravenous infusion of
      synthetic prostacyclin (iloprost) for eight days. Leg blood flow was measured
      with air plethysmography before treatment, on day 4 and day 8 of treatment. Total
      relief of pain for at least 6 weeks occurred in 91% of patients with leg blood
      flow > or = 40 ml/min, in 18% with leg flow 30-39 ml/min and in 11% with leg flow
      < 30 ml/min. Complete relief of pain for at least 6 weeks occurred in 92% of
      patients in whose limbs the blood flow on day 8 was greater than 50 ml/min but
      only in 6% with blood flow less than 50 ml/min. These results indicate that
      iloprost increases leg blood flow and that patients likely to respond can be
      identified from the baseline air plethysmographic measurement of leg blood flow.

PMID- 7505753
TI  - MHC restriction of T-cell proliferative responses in Xenopus.
AB  - The MHC restriction of Xenopus allogeneic MHC- and antigen-specific T-cell
      proliferative responses was assessed. Xenopus MHC-specific monoclonal antibodies
      that recognize class I and class II molecules were tested for inhibitory effects
      on the generation of secondary T-cell proliferative responses. Antigen-specific T
      cell lines were inhibited by anti-class II but not anti-class I monoclonal
      antibodies. Secondary alloantigen-specific proliferative responses also
      demonstrated MHC class II restriction. Allogeneic MHC- and antigen-specific T
      cell lines demonstrated differential sensitivity to anti-class II monoclonal
      antibodies directed at discrete class II epitopes. These results indicate that
      Xenopus T cells interact with antigen-presenting cells similarly to mammals, and
      directly confirm previous data indicating that MHC class II restriction of
      proliferative responses is present in amphibians.

PMID- 7505754
TI  - Comparison of the immune response to Ars-BGG in germfree or conventional piglets.
AB  - Neonatal germfree (GF) colostrum-deprived and conventional (CV) colostrum-fed
      piglets were immunized IP with p-azo-phenyl-arsonate-bovine gamma globulin (Ars
      BGG) in Freund's adjuvant to study the development of the immune response in the
      absence or presence of maternal antibodies and environmental antigens. Overall,
      the immune response varied greatly within each group but did not differ in GF
      from CV piglets statistically. Affinity immunoblot analysis suggested that anti
      Ars antibody was more restricted in GF than CV piglets and clonotype shifts
      occurred more in GF than CV piglets after each antigenic stimulation. In
      contrast, the clonotype pattern of the anti-BGG antibody was similarly
      heterogeneous in the two groups. Based on the affinity immunoblot data the
      antibodies generated to the Ars-haptenic group in CV piglets are more
      heterogeneous than GF piglets and suggest that clonotype generation is influenced
      by maternal antibodies and environmental antigens.

PMID- 7505755
TI  - Differential modulation of epidermal keratinization in immortalized (HaCaT) and
      tumorigenic human skin keratinocytes (HaCaT-ras) by retinoic acid and
      extracellular Ca2+.
AB  - The growth and differentiation response to retinoic acid (RA) was studied in the
      human keratinocyte line HaCaT and tumorigenic clones transfected with c-Ha-ras
      oncogene (HaCaT-ras). Differentiation (mainly keratin synthesis) was evaluated
      and correlated to cell proliferation in vitro but also growth behaviour in vivo
      (tumorigenicity). Comparable to normal keratinocytes, HaCaT cells and ras clones
      showed increased expression of the epidermal suprabasal keratins K1 and K10 upon
      RA depletion of the media (delipidized serum), while simple epithelial type
      keratins K7, K8 and K18 as well as K19 and K13 (typical of internal stratified
      epithelia) were almost completely suppressed. The cell density-dependent increase
      of K1 and K10 at intermediate RA levels (as in regular media with untreated
      serum) was also observed at Ca2+ levels below 0.1 mM, thus being clearly
      unrelated to stratification, whereas K13 synthesis was Ca(2+)-dependent and
      initiated with stratification. The effects on keratins were fully reversed by
      increasing RA concentrations. There was only mild stimulation of proliferation at
      RA doses (10(-10) to 10(-8) M) not directly corresponding to suppression of
      keratinization. Thus, the negative RA influence on K1 and K10, opposed to the
      effect on simple keratins, substantiates the preserved regulatory capacity
      rendering these cells appropriate models for biological testing. Among the
      various tumorigenic HaCaT-ras clones highly and moderately differentiating ones
      could be distinguished, accordingly induction in vitro led to a comparable
      spectrum of differentiation markers (K1 and K10 appearing early, and filaggrin
      late) as growth in vivo. These in vitro results demonstrate that, in spite of
      some differences in RA sensitivity, virtually all clones possess the epidermal
      differentiation repertoir which is regulated according to the same principles.
      Finally, this confirms our in vivo data that differentiation potential is not
      inversely related to the state of transformation or tumorigenicity.

PMID- 7505756
TI  - Retinoid regulation of human ectocervical epithelial cell transglutaminase
      activity and keratin gene expression.
AB  - Cornified envelope formation, the level of transglutaminase activity and the
      pattern of cytokeratin gene expression are important biochemical markers of
      cervical epithelial cell differentiation in vivo. In the present study we examine
      the effects of retinoid treatment on transglutaminase (TG) activity and keratin
      gene expression in cultured human ectocervical epithelial cells (ECE cells). All
      trans-retinoic acid (RA) and a synthetic retinoid, Ro 13-6298, suppress TG
      activity by 85-90% with half-maximal inhibition at 0.1 nM Ro 13-6298 or 1 nM RA.
      In contrast, the predominant circulating retinoid, retinol, does not inhibit TG
      activity. The level of type I transglutaminase protein, measured using a type I
      TG-specific antibody, decreases in parallel with the decrease in activity as does
      the level of the TG RNA transcript. Cytokeratin K16 decreases more than 20-fold
      while the level of K7, K8 and K19 increase 5 to 10-fold in the presence of 10 nM
      RA. Studies using cDNAs encoding K5, K13, K16 and K19 indicate that the RNA
      transcript levels change in parallel with the change in keratin protein
      production. Thus, all-trans-retinoic acid suppresses ectocervical epithelial cell
      differentiation in vitro, a result that suggests an in vivo role for retinoids in
      regulating cervical cell differentiation.

PMID- 7505757
TI  - Effect of TYB-2285 on antigen-induced histamine release from mouse bone marrow
      derived persisting cells (P-cells) primed with interleukin-3-containing
      conditioned medium (IL3-CM).
AB  - 1. The present study was carried out to investigate the effect of TYB-2285 [3,5
      bis(acetoxyacethylamino)-4-chlorobenzonitrile] on histamine release from
      persisting cells (P-cells) primed with interleukin-3-containing conditioned
      medium (IL3-CM). 2. IL3-CM enhanced antigen-induced histamine release from P
      cells, although IL3-CM did not affect spontaneous histamine release. 3. TYB-2285
      inhibited antigen-induced histamine release in the presence of IL3-CM, although
      it did not inhibit histamine release in the absence of IL3-CM. 4. The enhancement
      of histamine release by IL3-CM was reproduced by recombinant IL-3 (1-100 U/ml).
      5. These results demonstrate that TYB-2285 inhibits the histamine release primed
      with IL-3 and also suggests that TYB-2285 might regulate allergic inflammation in
      vivo by the suppression of mediator release primed with IL-3.

PMID- 7505758
TI  - Modulation of the automaticity by histamine and cimetidine in rabbit sino-atrial
      node cells.
AB  - 1. Effects of histamine (HIS) and cimetidine (CIM) on the spontaneous action
      potentials and ionic currents in rabbit sino-atrial node cells were investigated.
      2. HIS accelerated the sinus rate at 10 mumol/l, and shortened the action
      potential duration (APD) at 100 mumol/l, significantly. The positive effects were
      blocked by CIM (100 mumol/l), but not by diphenhydramine (DPH, 1 mumol/l). HIS
      (100 mumol/l) elicited a dysrhythmia in 4 out of 10 preparations. Addition of
      acetylcholine (ACh) (1 mumol/l) depressed the HIS-induced effects, but
      dysrhythmia occurred in 5 of 10 preparations. 3. CIM (100 mumol/l) caused a
      negative chronotropic effect. The APD was prolonged, and the Vmax was decreased.
      Addition of pindolol (0.1 mumol/l) potentiated the depressions. CIM (3 mmol/l)
      caused a sinus arrest in 3 out of 7 preparations. 4. In voltage-clamp
      experiments, HIS (100 mumol/l) enhanced the slow inward current (Isi). The
      delayed rectifying K+ current (IK) and hyperpolarization-activated inward current
      (Ih) were also increased. The enhancement was inhibited by CIM (100 mumol/l), but
      not by DPH (1 mumol/l). CIM (100 mumol/l) alone depressed Isi, IK and Ih.
      Pindolol (0.1 mumol/l) potentiated the CIM-induced depressions significantly. 5.
      These results suggest that HIS and CIM would modulate the ionic currents mediated
      through H2-receptors, and that HIS possesses arrhythmogenic action (probably by
      cAMP accumulation), which is potentiated by ACh.

PMID- 7505759
TI  - Histamine H3-receptor-induced inhibition of duodenal cholinergic transmission is
      independent of intracellular cyclic AMP and GMP.
AB  - 1. The inhibitory effect of the histamine H3-receptor agonist (R) alpha
      methylhistamine on cholinergic neurotransmission was studied in the isolated
      guinea pig duodenum in the presence of different compounds which alter
      intracellular levels of cyclic nucleotides and of the G proteins blocker
      pertussis toxin. 2. The action of (R) alpha-methylhistamine on electrically
      evoked contractions was not modified either by forskolin and
      isobutylmethylxanthine (which increase cyclic AMP) or by zaprinast and methylene
      blue (which increase and decrease, respectively intracellular cyclic GMP). Drugs
      affecting cyclic nucleotide levels were also ineffective against the inhibitory
      effect of the alpha 2 adrenergic agonist clonidine. 3. Pertussis toxin
      significantly reduced the maximum inhibition induced by (R) alpha-methylhistamine
      and clonidine, without influencing the effect of low concentrations of the above
      compounds; conversely it shifted to the right in a parallel way the inhibitory
      effect of adenosine. 4. These data suggest that H3-receptor-mediated inhibition
      of cholinergic transmission in the guinea pig duodenum is not linked to
      intracellular nucleotide changes. Moreover the signal transducing mechanism
      activated by (R) alpha-methylhistamine involves pertussis toxin both sensitive
      and insensitive G proteins.

PMID- 7505760
TI  - Conservation of surface epitopes in Pseudomonas aeruginosa outer membrane porin
      protein OprF.
AB  - The outer membrane proteins of several prominent bacterial pathogens demonstrate
      substantial variation in their surface antigenic epitopes. To determine if this
      was also true for Pseudomonas aeruginosa outer membrane protein OprF, gene
      sequencing of a serotype 5 isolate was performed to permit comparison with the
      published serotype 12 oprF gene sequence. Only 16 nucleotide substitutions in the
      1053 nucleotide coding region were observed; none of these changed the amino acid
      sequence. A panel of 10 monoclonal antibodies (mAbs) reacted with each of 46 P.
      aeruginosa strains representing all 17 serotype strains, 12 clinical isolates, 15
      environmental isolates and 2 laboratory isolates. Between two and eight of these
      mAbs also reacted with proteins from representatives of the rRNA homology group I
      of the Pseudomonadaceae. Nine of the ten mAbs recognized surface antigenic
      epitopes as determined by indirect immunofluorescence techniques and their
      ability to opsonize P. aeruginosa for phagocytosis. These epitopes were partially
      masked by lipopolysaccharide side chains as revealed using a side chain-deficient
      mutant. It is concluded that OprF is a highly conserved protein with several
      conserved surface antigenic epitopes.

PMID- 7505761
TI  - Phylogenic homogeneity of Coxiella burnetii strains as determinated by 16S
      ribosomal RNA sequencing.
AB  - DNA coding for the 16S rRNA of six strains of the obligate intracellular
      bacterium Coxiella burnetii was directly amplified from lysed host cells using
      the polymerase chain reaction. The amplification product was sequenced using a
      linear-PCR procedure and compared with other published 16S rRNA sequences. The
      results of this analysis confirm the position of C. burnetii in the gamma
      subgroup of the proteobacteria. The data show that all of the C. burnetii strains
      are highly related (> 99%) on the basis of 16S rRNA sequences although they had
      different geographic origins and phenotypic characteristics. The data support a
      phylogenetic homogeneity of the genus Coxiella with only one species which is C.
      burnetii.

PMID- 7505762
TI  - Expression of an amylase--alcohol dehydrogenase chimeric gene in transgenic
      strains of Drosophila melanogaster.
AB  - A chimeric gene, consisting of 428 bp of the promoter sequences of the alpha
      amylase gene of Drosophila melanogaster, fused to the transcribed region of the
      alcohol dehydrogenase (Adh) gene, was introduced into the genome of an Adhnull
      stock of Drosophila via P element mediated transformation. DNA analysis (Southern
      blotting) of three transformant strains confirmed the insertion of either one or
      two copies of the chimeric gene per strain. A histochemical study of ADH enzyme
      activity in dissected tissues of the transgenic larvae revealed that the chimeric
      Amy-Adh gene was expressed only in the posterior larval midgut and that this
      expression was repressed by dietary glucose, thus representing an expression
      pattern characteristic of the Amy gene. This indicates that the Amy upstream
      promoter sequences contain signals mediating both tissue specificity and glucose
      repression of the Adh structural gene in the transgenic larvae. The level of ADH
      activity expressed in transgenic flies was relatively low. This was paralleled by
      a low level of Adh mRNA, indicating a reduction in the transcriptional rate of
      the chimeric gene.

PMID- 7505763
TI  - [The supplemental motor area].
AB  - Following an introduction dealing with the developments which led to the
      discovery of the supplementary motor area (SMA), its anatomy and neuronal
      connections are described. Subsequently, a report concerning the pathology of the
      SMA (epilepsy, tumours, ablations, defects and possible neuroleptic effects) and
      related experimental findings is presented. This is followed by a description of
      the motor function, and especially the speech motor function of the SMA. The
      article concludes with an exposition of Sir John C. Eccles' interpretation of the
      SMA as providing the basis for a naive solution of the mind-body dualism.

PMID- 7505764
TI  - Effect of postischemic reperfusion on the pancreas.
AB  - In an examination of the effect of ischemia and reperfusion on the generation of
      active oxygen species during pancreatic cell damage, a short-term ischemia and
      reperfusion model was prepared by the occlusion and reperfusion of both the
      anterior mesenteric artery and the celiac artery in rats. Following 60 minutes of
      occlusion plus 7 hours of reperfusion of the anterior mesenteric artery and the
      celiac artery, the serum concentrations of amylase and lipase rose significantly
      to 7 and 6 times the respective control values. After 30 minutes of occlusion
      plus 7 hours of reperfusion, or after 7 hours of occlusion without reperfusion,
      amylase and lipase levels were not changed significantly. The continuous
      intravenous infusion of superoxide dismutase (3600 U/kg/hour) in rats receiving
      60 minutes of occlusion plus 7 hours of reperfusion suppressed the rise in serum
      amylase and lipase values to 25 percent of the values in the non-injected group.
      These results suggest that the active oxygen species which are generated by the
      short-term ischemia and reperfusion method injure the endothelium and cause
      hyperamylasemia and hyperlipasemia. Inhibition of the rise in serum amylase and
      lipase concentrations by pretreatment with a scavenger of active oxygen,
      superoxide dismutase, suggests that the active oxygen species are involved in the
      pathogenesis of acute pancreatitis.

PMID- 7505765
TI  - Palliative endoscopic treatment of malignant esophagorespiratory fistula: case
      report.
AB  - The authors report on a case of esophagorespiratory fistula due to squamous
      carcinoma of the esophagus treated on an emergency basis by endoscopic insertion
      of an Atkinson prosthesis following dilation of the malignant stenosis with
      Savary dilators. The authors suggest the endoscopic insertion of a prosthesis as
      the first approach in the emergency treatment of a malignant esophagorespiratory
      fistula because of the easiness of the technique, and its low morbidity and
      mortality rates; furthermore, this procedure relieves digestive and respiratory
      symptoms rapidly and reduces hospital stay while providing the patient with a
      better quality of remaining life.

PMID- 7505766
TI  - Expression of (cac)n/(gtg)n simple repetitive sequences in mRNA of human
      lymphocytes.
AB  - Di- and trinucleotide tandem repeat sequences are ubiquitously interspersed and
      are often polymorphic in the human genome. We have analyzed the transcription of
      simple (cac)n/(gtg)n repeats in the cDNA of RNA from human lymphocytes. When
      using such motifs as probes in RNA hybridization experiments, distinct signals
      are scarcely demonstrable. In order to investigate mRNA sequences that contain
      such simple repeats, 1 million phage clones from cDNA libraries were screened
      with the probe (CAC)5. From 50 hybridizing phages, 38 clones were successfully
      isolated and characterized. The lengths of the transcripts ranged from 120 bp to
      3.5 kb. More than 15 different additional simple repeat motifs were found
      immediately next to or distant to the (cac)n/(gtg)n repeat. In 12 clones,
      significant homologies were identified with a wide variety of unrelated genes,
      such as a processed pseudogene of human ubiquitin, serin protease inhibitor
      genes, a gene candidate from yeast, and sequence-tagged sites of man and mouse.
      Of the clones, 18% represented mRNA of MHC class I promotor binding protein; 79%
      displayed novel single copy sequences or partial similarity to many different
      organelle and nuclear genomes of animal, fungal, bacterial, and viral sequences.
      These data indicate that short (cac)n/(gtg)n stretches (n < or = 6) are sometimes
      contained in open reading frames, but more often in the 3' and 5' untranslated
      portions of mature mRNAs. Longer stretches of perfect simple (cac)n/(gtg)n
      repeats can rarely be recovered, even from the hnRNA of human lymphocytes.

PMID- 7505767
TI  - Exon 9 of the CFTR gene: splice site haplotypes and cystic fibrosis mutations.
AB  - The alternatively spliced exon 9 of the cystic fibrosis transmembrane conductance
      regulator (CFTR) gene codes for the initial part of the amino-terminal nucleotide
      binding fold of CFTR. A unique feature of the acceptor splice site preceding this
      exon is a variable length polymorphism within the polypyrimidine tract
      influencing the extent of exon 9 skipping in CFTR mRNA. We investigated this
      repeat for its relationship to CFTR mutations and intragenic markers on 200
      chromosomes from German patients with cystic fibrosis (CF). Four frequent length
      variations were strongly associated with the four predominant haplotypes
      previously defined by intragenic marker dimorphisms. One of these alleles
      displayed absolute linkage disequilibrium to the major CF mutation delta F508.
      Other frequent CFTR mutations were linked to one particular splice site haplotype
      indicating that differential exon 9 skipping contributes little to the clinical
      heterogeneity among CF patients with an identical mutation. We also identified a
      novel missense mutation (V456F) and a novel nonsense mutation (Q414X) within the
      coding region of exon 9. The missense mutation V456F adjacent to Walker motif A
      was present in a pancreas-sufficient CF patient. In contrast, the pancreas
      insufficient Q414X/delta F508 compound heterozygote suffered from a severe form
      of the disease, indicating that alternative splicing of exon 9 does not overcome
      the deleterious effect of a stop codon with this exon.

PMID- 7505768
TI  - Detection of a MspI restriction fragment length polymorphism for the human sex
      hormone-binding globulin (SHBG) gene.
AB  - A rare polymorphism in the human sex hormone-binding globulin (SHBG) gene was
      detected using a human SHBG cDNA probe. It is the first DNA sequence variation
      reported in this gene.

PMID- 7505769
TI  - Detection by the polymerase chain reaction of two polymorphisms in exon 14 of the
      human inter-alpha-trypsin inhibitor heavy chain H1 gene.
AB  - Two polymorphisms were detected within exon 14 of the inter-alpha-trypsin
      inhibitor heavy chain H1 (ITIH1) gene. The polymorphisms are detected by
      digesting the same 202-bp polymerase reaction product with the PstI and Hph1
      restriction endonucleases. These gene polymorphisms lead to the change of two
      amino acids in the mature protein. The polymorphisms can be used for the analysis
      of 3p21 deletion in human carcinomas as well as to develop a better understanding
      of the protein polymorphism already described.

PMID- 7505770
TI  - Recombinant vaccines against ovine footrot.
AB  - For the past 20 years footrot vaccines have evolved from simple bacterins to
      highly specific recombinant DNA (rDNA) fimbrial vaccines. The development of
      these vaccines has left a trail of discoveries, challenges and solutions; these
      processes continue as we move closer to understanding the requirements of a
      footrot vaccine. The initial whole cell vaccines were unsuccessful due to the
      short duration of immunity and incorporation of limited serotypes. A multistrain
      vaccine eliminated the problem of serotype inclusion, although the duration of
      immunity in many cases is still inadequate. The proteases of Dichelobacter
      nodosus appear to be cross protective; however, little is known of their ability
      to protect sheep against footrot. The major protective immunogen is the bacterial
      fimbriae, which also forms the basis for the K-agglutination serotyping system. K
      agglutinin titre correlates directly with resistance to challenge. The protective
      fimbrial epitope is conformationally dependent, suggesting little advantage in
      the development of synthetic peptide vaccines. To enhance the efficiency of
      vaccine production D. nodosus fimbrial genes were eventually cloned and
      successfully expressed in Ps. aeruginosa. Monovalent vaccines based on
      recombinant fimbriae are omnipotent, inducing high levels of agglutinins and long
      lasting immunity. In multivalent vaccines, on the other hand, incorporation of
      each additional serogroup into the vaccine results in reduced efficacy both in
      terms of reduced K-agglutinin titres and reduced protection following challenge.
      The least effective are multivalent formulations representing all major
      serogroups. In addition, considerable genetic variation has been observed in the
      ability of sheep to respond optimally to each serogroup in a multivalent vaccine.
      Results show that the limitation of the sheep to mount an effective immune
      response, rather than the quality or quantity of the immunogen, limits the
      efficacy of current footrot vaccines. Studies are being undertaken to examine in
      detail the immune response of sheep to potentially highly effective footrot
      vaccines.

PMID- 7505771
TI  - HCV infection in a north Indian hospital.

PMID- 7505772
TI  - Treatment of clinically fixed lymph node metastases from carcinoma of the penis
      by chemotherapy and surgery.
AB  - A 59-year-old patient with carcinoma of the penis was referred for therapy of
      clinically fixed and ulcerated bilateral inguinal lymphadenopathies. He was
      treated initially by partial penectomy and subsequently by weekly infusions of
      methotrexate, bleomycin and cisplatin. This treatment resulted in a decrease in
      the size of bilateral, lymphadenopathy and re-epithelization of the overlying
      ulcer. Subsequently a left-sided inguinal lymphadenectomy was performed. At
      follow-up 18 months later the symptoms had disappeared and no distant metastases
      were observed.

PMID- 7505773
TI  - Prostate-specific antigen kinetics after external beam irradiation for carcinoma
      of the prostate.
AB  - PURPOSE: A mathematical model that describes the kinetics of prostate-specific
      antigen measured in patients who received therapeutic doses of radiation therapy
      is presented. The clinical implications of the model are also investigated.
      METHODS AND MATERIALS: Data from 122 patients treated at Stanford University
      between December 1985 and December 1990 were used. The general form of the model
      contains five parameters, two associated with a decreasing exponential, two with
      a rising exponential and one additional constant. A nonlinear steepest-descent
      procedure that minimized chi-squared was used to determine the parameters
      producing the best fit to a patient's data. The correlation of the model
      parameters with clinical findings was investigated using standard statistical
      techniques including multivariate life-table and logistic regression. RESULTS:
      The data for all patients could be fit with either a decreasing exponential with
      or without the additional constant (nonrelapsing pattern with two or three
      parameters) or with a decreasing plus rising exponential (relapsing pattern with
      three or four parameters). In no instance were all five parameters of the general
      model required to describe a patient's data. Three of 61 patients with
      nonrelapsing patterns experienced clinical relapse, whereas 36 of 61 patients
      with relapsing patterns did. The logarithm of the initial prostate-specific
      antigen level and the corresponding model parameter correlated with T-stage and
      Gleason score. Among the patients with relapsing patterns, the nadir in antigen
      level occurred within 2 years of the start of treatment and the time to nadir, as
      calculated from the model parameters, was associated with the probability of
      clinical relapse. In no instance was the rate of initial decline ever exceeded by
      the rate of subsequent rise. CONCLUSION: The model is capable of describing the
      kinetics of prostate-specific antigen levels found in patients after receiving
      radiation therapy. The parameters derived from the model are strong correlates
      with clinical findings and patient outcome.

PMID- 7505774
TI  - Carcinoma of the prostate: praising Stanford's accomplishments.

PMID- 7505775
TI  - Predicting the risk of lymph node involvement using the pre-treatment prostate
      specific antigen and Gleason score in men with clinically localized prostate
      cancer.
AB  - PURPOSE: To evaluate the predictive value of an empirically derived equation for
      identifying patients with clinically localized prostate cancer at low and high
      risk for harboring occult lymph node metastasis. METHODS AND MATERIALS: A simple
      equation for estimating the risk of positive lymph nodes was empirically derived
      from a nomogram published by Partin et al. demonstrating the value of combining
      the pre-treatment prostate specific antigen and Gleason Score in predicting the
      risk of lymph node metastasis for patients with clinically localized prostate
      cancer. The risk of positive nodes (N+) was calculated using the equation; N+ =
      2/3(PSA) + (GS-6) x 10, where PSA and GS are the pre-treatment prostate specific
      antigen and Gleason Score respectively, and the calculated risk is constrained
      between 0-65% for a PSA < or = 40 ng/ml (as in the nomogram). To test the general
      applicability of this equation, we reviewed the pathologic features of 282 of our
      patients who had undergone a radical prostatectomy. RESULTS: Based on 212
      patients for whom the pre-operative prostate specific antigen's and Gleason
      Scores were available, we identified 145 patients with a calculated risk of
      positive nodes of < 15%, (low risk group) and 67 patients with a calculated risk
      as > or = 15% (high risk group). The observed incidence of positive nodes was 6%
      and 40% among the low and high risk groups respectively (p < 0.001). When used
      alone neither clinical stage, pre-treatment prostate specific antigen nor the pre
      treatment Gleason Score was as useful in identifying the largest low and high
      risk groups. CONCLUSION: Using the equation described we confirmed the general
      applicability of the nomogram reported by Partin et al. and identified patients
      at low and high risk for lymph node involvement. Based on these data we have
      adopted a policy of omitting whole pelvic irradiation in patients identified as
      low risk.

PMID- 7505776
TI  - Three-dimensional conformal radiation therapy in locally advanced carcinoma of
      the prostate: preliminary results of a phase I dose-escalation study.
AB  - PURPOSE: The acute morbidity of doses of 64.8-75.6 Gy and preliminary
      observations of late complications and tumor response using 3-dimensional
      conformal radiation therapy in carcinoma of the prostate are assessed. METHODS
      AND MATERIALS: 123 patients (Stage A2-12, B1-17, B2-43, C-51) were irradiated to
      the prostate and seminal vesicles using a 3-dimensional conformal radiation
      therapy technique. The median follow-up time was 15.2 months. The minimum tumor
      dose was 64.8-66.6 Gy in 49 patients, 70.2 Gy in 46, and 75.6 Gy in 28. Toxicity
      was scored according to the Radiation Therapy Oncology Group morbidity grading
      system. RESULTS: This technique of 3-dimensional conformal radiation therapy was
      well-tolerated with minimal acute morbidity. Only 32% of patients had grade 2 or
      3 acute morbidity requiring short-term medication for relief of urinary symptoms
      or diarrhea. Only one patient (0.8%) has so far developed a severe (grade 4) late
      complication. Serum prostate specific antigen concentrations normalized in 67% of
      patients (64/96) within 1-14 months (median 4.5 months) after treatment and were
      progressively decreasing at last measurement in an additional 22% (21/96).
      Abnormal rising prostate specific antigen levels were observed in 15 patients, 11
      of whom have already developed other evidence of relapsing disease. CONCLUSION:
      Acute toxicity for the doses tested with this 3-dimensional conformal radiation
      therapy technique is reduced compared to traditional treatment techniques, and
      the initial tumor response as assessed by prostate specific antigen measurement
      is highly encouraging with prostate specific antigen levels returning to normal
      in the majority of patients. Based on these results, a further increase of the
      dose to 81 Gy has been implemented in accordance with the schema of an ongoing
      Phase I dose-escalation study.

PMID- 7505777
TI  - Hodgkin's disease in the very young.
AB  - PURPOSE: A retrospective review of patients with Hodgkin's disease treated at
      Stanford University Medical Center was undertaken to determine if, within the
      pediatric population, children < or = 10 years of age have a unique prognosis and
      response to treatment. METHODS AND MATERIALS: Records of all patients treated for
      Hodgkin's disease at SUMC between 1961 and 1991 were reviewed. RESULTS: Of 2238
      patients with Hodgkin's disease, 91 (4%) were < or = 10 years of age. There is a
      predominance of male patients (80%) and a higher percentage of mixed cellularity
      (33%) and lymphocyte predominance (13%) histologies among the very young patients
      compared to adolescents and adults. The 5 and 10-year survival is 94 +/- 3% and
      92 +/- 3%, respectively, for children < or = 10 vs. 93 +/- 2% and 86 +/- 3% for
      adolescents and 84 +/- 1% and 73 +/- 1% for adults. Five and 10-year freedom from
      relapse is also higher in the youngest children (88 +/- 4% and 85 +/- 4%,
      respectively) compared to adolescents (78 +/- 3% and 74 +/- 3%, respectively) and
      adults (70 +/- 1% and 67 +/- 1%, respectively). Actuarial survival at 25 years
      for children < or = 10 years is 78%, which is slightly better than for
      adolescents (67%) and significantly better than for adults (41%) (p = 0.001).
      Actuarial 25-year freedom from relapse is also significantly better for children
      < or = 10 (78%) compared to adolescents (74% [p = 0.05]) and adults (65% [p =
      0.001]). For all stages of disease, children < or = 10 fare similarly to or
      slightly better than adolescents and substantially better than adults. For those
      with Stage I or II disease, survival at 5, 10, and 25 years is 98 +/- 2%, 93 +/-
      4% and 73%, respectively, for children aged < or = 10; 98 +/- 1%, 91 +/- 3%, and
      79%, respectively, for adolescents and 89 +/- 1%, 80 +/- 1%, and 45%,
      respectively, for adults. The greatest difference between age groups is seen for
      Stage III and IV patients. Those aged < or = 10 have an 89 +/- 5% 5 and 10-year
      survival, and 89% actuarial 25-year survival compared to 87 +/- 4%, 80 +/- 5%,
      and 28%, respectively, for adolescents and 77 +/- 2%, 64 +/- 2%, and 41%,
      respectively, for adults. Of patients < or = 10 years of age, 28 (31%) were
      treated with primary external beam radiotherapy, and 59 (65%) received combined
      modality therapy consisting of low-dose radiation and chemotherapy. With a median
      follow-up of 11 years, freedom from relapse is 64% and survival 75% for the
      radiotherapy group, compared to 97% (p = 0.000) and 93% (p = 0.21) for those
      treated with combined modality therapy. CONCLUSION: Results indicate that young
      age is a favorable prognostic factor in Hodgkin's disease. Combined modality
      therapy has led to improved freedom from relapse and survival rates for all
      stages of disease and is currently the treatment of choice for the majority of
      very young children.

PMID- 7505778
TI  - Development of the peptidergic innervation of human heart.
AB  - The aim of the present investigation was to study the developing peptidergic
      innervation of the human fetal heart of 7-24 wk gestational age. An
      immunohistochemical approach was adopted and the total innervation visualised
      with antisera to general neuronal and Schwann cell markers, while the onset and
      development of specific neuropeptide-containing subpopulations were investigated
      using antisera to neuropeptide Y (NPY), somatostatin, vasoactive intestinal
      polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP).
      Cardiac ganglia and nerves were demonstrated from 7 wk of gestation whereas
      peptide-immunoreactive nerves were not observed until the 10th week of gestation.
      NPY-immunoreactive nerve fibres constituted the major subpopulation of peptide
      containing nerves identified in the fetal heart, exhibiting a descending atrial
      to ventricular density gradient, and were first identified during the 10th wk of
      gestation. Somatostatin- and VIP-immunoreactive nerves appeared at 10-12 wk of
      gestation and were mainly distributed in the atria. Somatostatin immunoreactivity
      was localised to cell bodies in cardiac ganglia, as well as to nerve fibres,
      indicating an intrinsic origin for this nerve subpopulation. Conversely, the
      other peptide-containing nerves appear to be of extrinsic origin, including those
      immunoreactive for VIP. Intracardiac neurons exhibit a transient expression of
      tyrosine hydroxylase immunoreactivity. Putative sympathetic nerve fibres,
      displaying tyrosine hydroxylase and NPY immunoreactivity, were demonstrated
      before the adrenergic innervation has previously been shown to be present by
      formaldehyde-induced fluorescence staining of catecholamines. The onset of the
      CGRP- and SP-immunoreactive innervation, at 18-24 wk of gestation, followed the
      appearance of other peptide-containing nerves, suggesting that the sensory,
      afferent innervation occurs later than the autonomic. The differential appearance
      and distribution of peptide-containing nerve subpopulations indicate that there
      is a chronological order to the development of the autonomic and sensory
      components of human cardiac innervation.

PMID- 7505779
TI  - Reconsideration of the development of the distal tubule of the human kidney.
AB  - The human kidney develops from 2 embryonic tissues, the ureteric bud and the
      metanephric blastema. The site in the adult renal distal tubule corresponding to
      the junction between these tissues has never been established unequivocally and
      is usually said to be the union between the collecting duct and the connecting
      piece, based on microdissection evidence. We have examined kidneys from 21 human
      fetuses of various ages using an immunohistological method for substances related
      to the ABO blood group system, various cytokeratins including those detected by
      the monoclonal antibody PKK2, and Tamm-Horsfall protein. The ureteric bud and
      connecting piece expressed the type 1 precursor chain of ABO antigens mostly
      early in gestation, the H antigen of the ABO system mostly later in gestation,
      and cytokeratins detected by PKK2. The induced nephrons after the S-shaped body
      stage expressed Tamm-Horsfall protein. In the adult renal tubule, distal from the
      macula densa, it was already known that there is a sharp junction between the
      segment expressing Tamm-Horsfall protein and the more distal segment that
      expresses the H antigen and cytokeratins detected by PKK2. The finding that the
      ureteric bud and connecting piece express the same antigens as this segment while
      the S-shaped body eventually expresses Tamm-Horsfall protein is consistent with
      the concept that (1) the connecting piece arises from the ureteric bud, not the S
      shaped body, and (2) the junction of ureteric bud derivatives and metanephric
      blastema derivatives is on the distal side of the macula densa at the distal end
      of Tamm-Horsfall staining.

PMID- 7505780
TI  - VCAM-1 is a CS1 peptide-inhibitable adhesion molecule expressed by lymph node
      high endothelium.
AB  - Previous studies have shown that unactivated lymphocytes bind to CS1 peptide and
      that the adhesion of these cells to high endothelium is inhibited by CS1 peptide.
      These results suggest that lymphocyte binding occurs via recognition of the CS1
      containing splice variant of fibronectin expressed on the high endothelial
      surface. We have now extended these studies by determining the role of the CS1
      receptor, alpha 4 beta 1 (VLA-4) and the alternative VLA-4 ligand, VCAM-1 in a
      rat model of lymphocyte-high endothelial cell interaction. Anti-VLA-4 antibody,
      HP2/1, blocked lymphocyte adhesion to resting and IFN-gamma (interferon-gamma)
      pretreated cultured high endothelial cells (HEC) in a dose-dependent manner with
      maximal inhibition of 60%. HP2/1 completely blocked the adhesion of rat
      lymphocytes to immobilized CS1 peptide and to a recombinant soluble (rs) form of
      human VCAM-1. Lymphocyte binding to rsVCAM-1 was also completely blocked by CS1
      peptide. Anti-rat VCAM-1 monoclonal antibody 5F10 inhibited adhesion to untreated
      and IFN-gamma-treated HEC equally and its effect at 50% inhibition was slightly
      less than that of HP2/1. These findings suggest that a CS1 peptide-inhibitable
      ligand expressed by high endothelium is VCAM-1. The majority of cultured HEC
      expressed significant levels of VCAM-1 under basal conditions, as did HEV in
      peripheral lymph nodes. VCAM-1 expression by HEC was upregulated by cytokine
      pretreatment and the effects were ordered: IFN-gamma > TNF-alpha > IL-1 beta. The
      results described here demonstrate that rat peripheral lymph node HEC express
      VCAM-1, its expression is upregulated by cytokines, in particular IFN-gamma, and
      it supports the adhesion of unactivated lymphocytes. They also suggest that the
      VLA-4/VCAM-1 adhesion pathway may operate during the constitutive migration of
      lymphocytes into lymphoid organs. Although the mechanism of CS1 peptide
      inhibition was not determined, these results show that VCAM-1 is a CS1 peptide
      inhibitable ligand and therefore CS1, on its own, cannot be used as a specific
      indicator of fibronectin activity.

PMID- 7505781
TI  - Regulation of keratinocyte terminal differentiation by integrin-extracellular
      matrix interactions.
AB  - Suspension-induced terminal differentiation of human epidermal keratinocytes can
      be inhibited by fibronectin through binding to the alpha 5 beta 1 integrin. We
      have investigated the effect of fibronectin on expression of integrins and
      proteins of the actin cytoskeleton and have explored the nature of the
      differentiation stimulus by testing different combinations of anti-integrin
      monoclonal antibodies or extracellular matrix proteins in the suspension assay.
      Fibronectin prolonged cell surface expression of beta 1 integrins but did not
      overcome the inhibition of intracellular transport of integrins that occurs when
      keratinocytes are placed in suspension. Fibronectin did not prevent the
      suspension-induced decline in the level of mRNAs encoding the beta 1 integrin
      subunit, actin, filamin and alpha-actinin; furthermore, the inhibition of
      terminal differentiation did not depend on the state of assembly of
      microfilaments or microtubules. Terminal differentiation could be partially
      inhibited by an adhesion-blocking monoclonal antibody to the beta 1 integrin
      subunit or by a combination of adhesion blocking antibodies recognising the alpha
      subunits that associate with beta 1 (alpha 2, alpha 3 and alpha 5). Although
      laminin and type IV collagen do not inhibit terminal differentiation
      individually, they were inhibitory when added to cells in combination with a low
      concentration of fibronectin. We conclude that the proportion of keratinocyte
      beta 1 integrins occupied by ligand can regulate the initiation of terminal
      differentiation independently of the state of assembly of the actin cytoskeleton.

PMID- 7505782
TI  - Retinoic acid mediates post-transcriptional regulation of keratin 19 mRNA levels.
AB  - Stratified squamous epithelia have been shown to preferentially express a site
      specific pattern of keratin intermediate filaments. Retinoic acid (RA) is known
      to modulate expression of the basal cell keratins K19 and K5. Expression of these
      genes is dependent on extracellular RA concentration. We have found that K19 mRNA
      levels increase over time in cultured keratinocytes exposed to elevated
      concentrations of RA. K5 mRNA levels decrease in response to RA in a similar
      fashion. The observed changes in K5 message are primarily the result of RA
      induced alterations in gene transcription. However, the RA-mediated induction of
      K19 mRNA is not the result of increased transcription but is primarily due to
      enhanced mRNA stability. These results suggest that an RA-dependent post
      transcriptional mechanism modulates K19 intermediate filament expression in
      stratified squamous epithelia.

PMID- 7505783
TI  - The globular head domain of titin extends into the center of the sarcomeric M
      band. cDNA cloning, epitope mapping and immunoelectron microscopy of two titin
      associated proteins.
AB  - Immunoelectron microscopical results have shown that the Z and M bands of the
      sarcomere are interconnected by the long titin molecules. Here we have
      characterized by monoclonal antibodies, cDNA cloning and immunoelectron
      microscopy the two titin-associated proteins (190 and 165 kDa proteins), which
      seem responsible for the formation of a head structure on one end of the 0.9
      micron long titin string. The human 165 kDa (1465 residues) and 190 kDa (1451
      residues) proteins have unique N-terminal domains some 110 residues in length.
      Both proteins show 12 repeat domains with strong homology to either fibronectin
      type III (motif I) or immunoglobulin C2 (motif II) domains, which are arranged in
      the order II-II-I-I-I-I-I-II-II-II-II-II. Over these repeat domains the two
      proteins share 50% sequence identity (70% similarity). Epitopes situated in the C
      terminal 138 or in the preceding 206 residues of the 165 kDa protein locate in
      immunoelectron microscopy to stripes situated 18 or 15 nm from the center of the
      M band. An epitope situated 277 to 129 residues prior to the C-terminus of the
      190 kDa protein (i.e. repeats 10 and 11) locates to the center of the M band.
      Thus the head structure of the titin molecule extends into the center of the M
      band. Microsequence data on peptides from the titin-associated bovine 165 kDa
      protein and from conventionally purified bovine M-protein argue together with the
      reactivity of the antibodies that 165 kDa protein and M-protein are identical.
      The integrating structure of the sarcomere, which is based on titin and its side
      on (C-protein and 86 kDa protein) or end-on (190 kDa protein and 165 kDa protein)
      associated proteins arises from muscle-specific members of the superfamily of
      immunoglobulin-like proteins.

PMID- 7505784
TI  - Internalization of hyaluronan by chondrocytes occurs via receptor-mediated
      endocytosis.
AB  - Several studies have suggested that chondrocytes must have the capacity to
      internalize and degrade extracellular hyaluronan. In the present study we show
      direct evidence that hyaluronan is, in fact, endocytosed by chondrocytes and that
      the endocytosis is mediated via cell surface CD44/hyaluronan receptors. Cultures
      of bovine articular chondrocytes as well as rat chondrosarcoma chondrocytes were
      incubated with either fluorescein- or 3H-labeled hyaluronan. Intense binding and
      accumulation of labeled hyaluronan was visualized by fluorescence microscopy or
      bright-field/dark-field microscopy following autoradiography. Cell surface
      hyaluronan was removed with either trypsin or Streptomyces hyaluronidase in order
      to distinguish and quantify intracellular endocytosed hyaluronan. Labeled
      hyaluronan was visualized within small discrete intracellular vesicles
      distributed throughout the cytoplasm. Binding and endocytosis of fluorescein- or
      3H-labeled hyaluronan was totally blocked by the addition of excess unlabeled
      hyaluronan or hyaluronan hexasaccharides, competitive inhibitors of
      hyaluronan/hyaluronan receptor interactions. Binding and endocytosis was also
      blocked by the addition of anti-CD44 monoclonal antibodies. Characterization of
      endocytosed 3H-labeled hyaluronan demonstrated that a significant portion of the
      hyaluronan was degraded by both the bovine articular and rat chondrosarcoma
      chondrocytes. Interestingly, a higher proportion of bound hyaluronan was
      internalized by the bovine chondrocytes. Therefore, hyaluronan receptor-mediated
      endocytosis and degradation of hyaluronan may provide a critical link to the
      maintenance and homeostasis of cartilage tissue.

PMID- 7505785
TI  - Endothelial cells adhere to the RGD domain and the fibrinogen-like terminal knob
      of tenascin.
AB  - We have found that endothelial cells adhere much more strongly than fibroblasts
      to domains of tenascin and fibronectin. Endothelial cells adhered weakly, without
      spreading, to bacterial expression proteins corresponding to the tenth
      fibronectin type III (FN-III) domain of fibronectin, which contains the RGD. A
      larger fibronectin protein, containing this domain and the three amino-terminal
      'synergy' domains gave strong adhesion and spreading. Two widely separated
      domains of tenascin gave adhesion. The third FN-III domain, TNfn3, which contains
      an RGD sequence in human and chicken tenascin, gave very strong adhesion and
      spreading of endothelial cells when tested as an isolated domain. Larger segments
      containing TNfn3 and the adjacent TNfn2 gave weaker adhesion, probably because
      the RGD sequence is partially blocked. Adhesion to this domain required divalent
      cations, was exquisitely sensitive to soluble GRGDSP peptide, and was blocked by
      antisera to the integrin alpha v beta 3. The second tenascin adhesion domain was
      the fibrinogen-like C-terminal knob, TNfbg. Cells adhered to but did not spread
      on this domain. This adhesion required divalent cations and was also sensitive to
      GRGDSP peptide, so it may be mediated by an integrin receptor. We have explored a
      range of conditions for preparing the adhesion substratum, and our results may
      resolve the controversy over whether tenascin can act as a substratum adhesion
      molecule. When coated for short times (1-2 hours) on plastic, tenascin had no
      adhesion activity, in contrast to fibronectin and the expression proteins, which
      gave strong adhesion under these conditions. When coated for longer times (12-24
      hours) on plastic, the tenascin substratum supported good adhesion, but not
      spreading, of endothelial cells. Tenascin coated on nitrocellulose gave
      substantially stronger adhesion than on plastic, but still required long coating
      times for maximal activity. Adhesion of endothelial cells to native TN was
      inhibited by GRDGSP peptide. The cell adhesion activity demonstrates the presence
      on endothelial cells of tenascin receptors, which may play a supportive role in
      angiogenesis, in the structure of blood vessels, or in binding tenascin to the
      cell surface to elicit or enhance a signalling function.

PMID- 7505786
TI  - Chemiluminescent and colorigenic detection of cherry leaf roll virus with
      digoxigenin-labeled RNA probes.
AB  - Digoxigenin-labeled RNA probes were used to detect cherry leaf roll virus in
      infected plants. A dot-blot hybridization immunoenzymatic assay in both crude sap
      extracts and partially purified tissue with a colorigenic and chemiluminescent
      detection was developed. The use of the new AMPPD substrate was found to be
      effective in clarified sap extracts in conditions were the colorigenic detection
      method failed. Both detection assays were effective when using unfractionated
      nucleic acid preparations, the chemiluminescent being five times more sensitive
      than the colorigenic. The chemiluminescent hybridization assay makes it possible
      to detect the virus at the picogram level. The non-radioactive dot-blot
      hybridization techniques described here turned out to be very suitable for plant
      virus diagnosis. The sensitivity of this method and those obtained by ELISA or
      radioactive dot-blot described previously is compared.

PMID- 7505787
TI  - A weight reduction intervention that optimizes use of practitioner's time, lowers
      glucose level, and raises HDL cholesterol level in older adults.
AB  - OBJECTIVE: The effects of a cognitive-behavioral weight control intervention were
      compared in two independent-living, older adult (mean age = 70.5 years)
      communities. DESIGN: The research design compared the experimental community (n =
      163), which received the intervention, with the control community (n = 162).
      SUBJECTS: Overweight individuals (> 4.5 kg of age-adjusted weight according to
      height-weight tables) were recruited from both communities. INTERVENTION:
      Components of the Dietary Intervention: Evaluation of Technology (DIET) program
      included a video-tape, a workbook, computerized tracking of participants, a
      telephone hot line, educational group discussions, and individual consultation.
      OUTCOME MEASURES: Changes in body weight, body mass index, and lipid and glucose
      measures were selected to evaluate the effectiveness of the intervention.
      STATISTICAL ANALYSIS: One-way analysis of variance by group was done to compare
      changes in continuous variables between the intervention and control communities.
      RESULTS: Baseline body mass index and weight were 30.8 and 79.5 kg, respectively,
      in the experimental community and 28.8 and 75.8 kg, respectively, in the control
      community. Mean weight change in the experimental community was -3.2 kg after 40
      weeks of intervention, compared with no weight change in the control community (P
      < .0001). Mean plasma glucose level decreased -0.3 mmol/L and mean high-density
      lipoprotein cholesterol level increased 0.15 mmol/L in the experimental
      community, compared with no change in lipid parameter and a +0.3 mmol increase in
      glucose level in the control community (P < .0001). APPLICATIONS: Our findings
      suggest that an intervention that optimizes use of the practitioner's time can
      achieve a moderate weight loss and metabolic improvement in a community of older
      adults.

PMID- 7505788
TI  - Elephant seal genetic variation and the use of simulation models to investigate
      historical population bottlenecks.
AB  - Because the northern elephant seal (Mirounga angustirostrus) was heavily
      exploited during the 19th century, it experienced an extreme population
      bottleneck. Since then, under legislative protection in the United States and
      Mexico, northern elephant seals have recovered dramatically in number, although
      their genomic diversity was greatly reduced, apparently as a consequence of the
      bottleneck. In this study we investigated DNA sequence diversity in two mtDNA
      regions (the control region and 16S RNA) and found low genetic variation in the
      northern elephant seal: there were only two control region haplotypes (sequence
      difference = 1%), which was consistent with an extreme founder event in the
      recent history of the northern species. We also reaffirmed the lack of allozyme
      diversity in this species. In contrast, the southern elephant seal (M. leonina),
      which though similarly exploited never fell below 1,000 animals, had 23 control
      region mtDNA haplotypes (average sequence difference = 2.3%). To investigate the
      extent of the founder event in the northern elephant seal we devised a simulation
      model based on extensive demographic data. This allowed a statistical analysis of
      the likely outcome of bottlenecks of different size and duration. Given these
      historical data, our results indicate (within 95% confidence) a bottleneck of
      less than 30 seals and 20-year duration, or, if hunting was the primary pressure
      on the population, a single-year bottleneck of less than 20 seals.

PMID- 7505789
TI  - A Phaseolus lectin anterograde tracing study of the rotundo-telencephalic
      projections in the domestic chick.
AB  - Phaseolus vulgaris leucoagglutinin extracellular injection was performed in
      nucleus rotundus thalami and the course of labelled fibers and their termination
      were examined in chicken. The labelled fibers terminate in ectostriatum centrale,
      ectostriatum perifericum and neostriatum intermedium. The course and termination
      of the fibers are analysed in detailed.

PMID- 7505790
TI  - Pattern of organization of primary visual pathways in the European lizard
      Podarcis sicula Rafinesque.
AB  - Central visual pathways are similarly organized in all vertebrates, although
      differences are also evident in the distribution of retinofugal axons in mammals,
      birds and reptiles. We traced the retinofugal projections in the European lizard
      Podarcis sicula Rafinesque and compared our observations with previous findings
      in other reptilian species, as well as in mammals and in birds, in order to
      contribute to the understanding of similarities and differences in the pattern of
      organization of visual pathways in these vertebrate classes. Either HRP or 3H
      proline injections were placed into one eye. No differences in staining pattern
      were observed between HRP and 3H-proline experiments. Prominent retinofugal
      projections were observed to the thalamic nuclei nucleus dorsolateralis, nucleus
      geniculatus lateralis dorsalis, nucleus geniculatus lateralis ventralis and
      nucleus geniculatus lateralis ventralis, pars ventralis. In the hypothalamus the
      suprachiasmatic nucleus, and in the pretectum nuclei geniculatus pretectalis,
      lentiformis mesencephali and posterodorsalis contained detectable amounts of
      labeled terminals. Retinal fibers were distributed to layers 14 and 12 of the
      optic tectum and terminated in layers 13, 11, and 8. Labeled fibers were also
      present in the basal optic tract, and terminals were located in the nucleus of
      the basal optic tract. Ipsilateral retinofugal fibers were detected in the optic
      tract, and terminals were observed in the same thalamic and pretectal nuclei
      which receive crossed projections. No terminals in the ipsilateral tectal layers
      could be demonstrated. Compared to the crossed projection, the ipsilateral
      retinofugal contingent was very small. These results confirm and extend data from
      previous studies in reptiles and are consistent with the distribution of
      retinofugal fibers found in other vertebrates. The presence of ipsilateral
      retinofugal projections represents a common feature of the organization of visual
      pathways in reptiles, although its importance for binocular interactions remains
      to be elucidated.

PMID- 7505791
TI  - Presentation of human neocortical neurons stained with the carbocyanine dye dil
      compared to the Golgi silver impregnation technique.
AB  - The carbocyanine dye Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate) not only serves as an excellent neuronal tracer, but also produces
      staining of neurons similar to the results of the Golgi technique. In one aspect
      staining with Dil seems superior to the Golgi technique: the axons are well
      stained and show morphological details of their structure. The dendrites and the
      spines can also be studied easily so that this technique seems to be a promising
      alternative of the Golgi technique. The fading of the fluorescence could probably
      be overcome by photoconversion of the stained neurons.

PMID- 7505792
TI  - Synaptic organization and prefrontal corticothalamic termination in the
      mediodorsal thalamic nucleus of the cat.
AB  - The synaptic organization of the mediodorsal thalamic nucleus (MD) in the cat
      have been studied with the electron microscope, and correlated with the
      termination of the medial prefrontal corticothalamic afferents using the method
      of anterograde transport of wheat germ agglutinin conjugated to horseradish
      peroxidase (WGA-HRP). The neuropil of MD was divided into glomerular and
      extraglomerular regions. A synaptic glomerulus was composed of a central dendrite
      and some different presynaptic profiles with astroglial ensheathment. The
      prevalent presynaptic elements in glomeruli were presynaptic dendrites (PSDs)
      that contained pleomorphic vesicles, and formed symmetric synaptic contacts and
      puncta adhaerentia junctions with central dendrites. One or two large terminals
      with round vesicles and asymmetric specializations (LR) also participated in
      glomerular formations. They were invariably presynaptic to central dendrites and
      PSDs. As terminals less frequently found within glomeruli, there were small-sized
      terminals with round vesicles and asymmetric synaptic junctions with PSDs. In the
      extraglomerular neurophils, small to medium-sized terminals with pleomorphic
      vesicles (SMP) were found besides the presynaptic profiles identified in
      glomerular regions. These SMP terminals formed axodendritic and axosomatic
      symmetric synapses. WGA-HRP injections into the medial prefrontal cortex resulted
      in anterograde labelings in not only SR but also LR presynaptic terminals. SR
      boutons made up the majority of labeled terminals, and they were found only in
      the extraglomerular neuropil. While labeled LR terminals were detected in the
      extraglomerular neuropil and synaptic glomeruli with less encounter. The results
      of the present study show that the synaptic organization in MD of the cat is
      similar to that in other thalamic relay nuclei and in MD of the monkey. Further,
      MD receiving two subsets of synaptic terminations from the prefrontal cortex
      might play a different functional role in regulating the neural circuit between
      MD and the prefrontal cortex in comparison with that in the sensory and motor
      thalamic nuclei that receive only SR terminals from the sensorimotor cortex.

PMID- 7505793
TI  - Immunological specificity of Helicobacter pylori urease and identification by
      immunological detection of its specific urease.
AB  - Helicobacter pylori urease was recovered as a single peak by DEAE-Sepharose
      column chromatography and Sephacryl S-200 gel filtration. The purified urease was
      obtained by fast protein liquid chromatography using a Mono Q column. The
      purified urease preparation gave a single band in polyacrylamide gel disc
      electrophoresis. Latex particles were sensitized with anti-urease immunoglobulin.
      The sensitized latex particles were agglutinated with the purified urease and by
      cell sonicates obtained from 55 strains of H. pylori which were isolated from the
      gastric mucosa of patients with gastric and duodenal disorders, while they did
      not react with those obtained from related bacteria known to be urease producers,
      such as Helicobacter mustelae and urease- positive "Campylobacter lari variants",
      or by urease of some strains of Enterobacteriae. We have developed a specific and
      sensitive method for detecting the urease by using the reversed passive latex
      agglutination technique, in order to identify of the organism.

PMID- 7505794
TI  - [Influence of granulocyte colony-stimulating factor on bactericidal activities of
      macrophages and polymorphonuclear leukocytes].
AB  - We investigated the influence of granulocyte colony-stimulating factor (G-CSF) on
      bactericidal activities of macrophages and polymorphonuclear leukocytes (PMNs)
      from experimental pyelonephritis in leukocytopenic rats, in order to clarify the
      usefulness of G-CSF for opportunistic pyelonephritis. We prepared three groups of
      experimental pyelonephritis, i.e., G-CSF administration group (group-1),
      cyclophosphamide (CPA) administration group (group-2), and CPA and G-CSF
      administration group (group-3). And we measured the active oxygen generation of
      peritoneal macrophages and PMNs in each group. On the other hand, we produced
      pseudomonal pyelonephritis in each group, and compared the survival rate of each
      group for 7 days. G-CSF enhanced active oxygen generation of peritoneal
      macrophages and PMNs, significantly. Furthermore, G-CSF improved the survival
      rate of pseudomonal pyelonephritis in leukocytopenic rats. These results indicate
      that G-CSF enhanced bactericidal activities of macrophages and PMNs in vivo, and
      prevents dissemination of infections.

PMID- 7505795
TI  - Nosocomial outbreak of Pseudomonas cepacia respiratory infection in
      immunocompromised patients associated with contaminated nebulizer devices.
AB  - From May 1990 to August 1991, 36 patients admitted to the Department of Internal
      Medicine in a medical school hospital with hematological malignancies or solid
      tumors, developed respiratory tract colonization with Pseudomonas cepacia.
      Sixteen (44.4%) of these patients developed pneumonia, and four (11.1%) died of
      respiratory failure due to P. cepacia pneumonia. Extensive survey of the hospital
      environment as well as equipment showed that nebulizer devices used by the
      patients for inhalation were contaminated with P. cepacia. Phenotypic
      characteristics, (production of hemolysin and extracellular enzymes [lipase,
      lecithinase and protease]), the Analytical Profile Index 20 NE pattern, and the
      pattern of DNA fingerprinting by pulse-field gel electrophoresis in clinically
      isolated strains and strains derived from nebulizer devices were compared. The
      strains of P. cepacia obtained from patients in the Department of Internal
      Medicine were indistinguishable from each other and also from those isolated from
      nebulizer devices, but were different from those isolated from patients in other
      departments at the same time. These results demonstrated that the outbreak of P.
      cepacia respiratory colonization in immunocompromised patients was a nosocomial
      acquisition, and probably occurred by transmission through contaminated nebulizer
      devices.

PMID- 7505796
TI  - [Cloned mammalian DNA repair enzymes with special emphasis on AP endonuclease].

PMID- 7505797
TI  - Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic
      cells permits growth factor receptor-independent link to ras activation pathway.
AB  - Enforced expression of p210bcr-abl transforms interleukin 3 (IL-3)-dependent
      hematopoietic cell lines to growth factor-independent proliferation. It has been
      demonstrated that nonreceptor tyrosine kinase oncogenes may couple to the p21ras
      pathway to exert their transforming effect. In particular, p210bcr-abl was
      recently found to effect p21ras activation in hematopoietic cells. In this
      context, experiments were performed to evaluate a protein signaling pathway by
      which p210bcr-abl might regulate p21ras. It was asked whether Shc p46/p52, a
      protein containing a src-homology region 2 (SH2) domain, and known to function
      upstream from p21ras, might form specific complexes with p210bcr-abl and thus,
      possibly alter p21ras activity by coupling to the guanine nucleotide exchange
      factor (Sos/CDC25) through the Grb2 protein-Sos complex. This latter complex has
      been previously demonstrated to occur ubiquitously. We found that p210bcr-abl
      formed a specific complex with Shc and with Grb2 in three different murine cell
      lines transfected with a p210bcr-abl expression vector. There appeared to be a
      higher order complex containing Shc, Grb2, and bcr-abl proteins. In contrast to
      p210bcr-abl transformed cells, in which there was constitutive tight association
      between Grb2 and Shc, binding between Grb2 and Shc was Steel factor (SLF)
      dependent in a SLF-responsive, nontransformed parental cell line. The SLF
      dependent association between Grb2 and Shc in nontransformed cells involved
      formation of a complex of Grb2 with c-kit receptor after SLF treatment. Thus,
      p210bcr-abl appears to function in a hematopoietic p21ras activation pathway to
      allow growth factor-independent coupling between Grb2, which exists in a complex
      with the guanine nucleotide exchange factor (Sos), and p21ras. Shc may not be
      required for Grb2-c-kit interaction, because it fails to bind strongly to c-kit.

PMID- 7505798
TI  - Recognition of an immunoglobulin VH epitope by influenza virus-specific class I
      major histocompatibility complex-restricted cytolytic T lymphocytes.
AB  - There are two immunogenic sites on the type A influenza A/Japan/57 (H2N2)
      hemagglutinin (HA) that can be recognized by class I major histocompatibility
      complex (MHC), H-2Kd-restricted cytolytic T lymphocytes (CTLs). One of these
      sites encompasses two distinct partially overlapping epitopes, which span HA
      residues 204-212 and 210-219. During the analysis of the fine specificity of CTL
      clones directed to the HA 210-219 epitope, we found that one clone 40-2 also
      recognized the myeloma cell line P3x63-Ag8. P3x63-Ag8 is derived from the MOPC 21
      myeloma and expresses an immunoglobulin (Ig) heavy chain variable region (VH)
      gene which is a member of the murine 7183 VH gene family. Recognition was
      specific for the endogenously processed MOPC 21 heavy chain in association with
      the Kd molecules, since the SP2/0 derivative of P3x63-Ag8, which does not make a
      functional Ig H chain, is not recognized. The VH epitope recognized by clone 40-2
      could be mapped to a 10 amino acid peptide spanning MOPC 21 VH residues 49-58.
      Cross-reactivity for the VH gene product was also demonstrable in some
      heterogeneous populations of CTL generated in response to influenza virus
      infection. These results represent the first demonstration of cross-reactivity
      for an endogenously processed product of a self-Ig by the CTL directed to a
      foreign antigen and raise the possibility that the Ig VH expression may regulate
      the CD8+ T cell response to foreign antigens.

PMID- 7505799
TI  - Tolerogenicity of resting and activated B cells.
AB  - Antigen presentation by resting splenic B cells has been shown previously to
      induce T helper 1 cell (Th1) anergy. In contrast to expectations, it was found
      here that B cells treated with F(ab')2 goat anti-mouse immunoglobulin (IgM) for
      24 or 48 h also presented antigen (Ag) to Th1 cells in a manner that induced
      dramatic Ag-specific proliferative inactivation. The tolerogenicity of the anti
      Ig-treated B cells was consistent with the observation that these B cells were
      only slightly more efficient than resting B cells in stimulating human gamma
      globulin (HGG)-induced proliferation of HGG-specific Th1 cells in primary
      cultures. The activated B cells were, however, more efficient than resting B
      cells in stimulating a primary mixed leukocyte reaction, and exhibited increased
      expression of major histocompatibility complex class II molecules, RL388 Ag and
      transferrin receptor. In addition, unlike resting B cells, which expressed little
      detectable B7, anti-Ig-treated B cells expressed high levels of B7. The
      functional capacity of the B7 expressed on the activated B cells was demonstrated
      by the fact that the Ag-presenting capacity of these B cells was inhibited by the
      addition to culture of CTLA4Ig, a soluble receptor for B7. It is unlikely that
      the tolerogenicity of the activated B cells was due to an inability of the Th1
      cells to respond to B7 signals; the Th1 clones used in the experiments, unlike
      the Th2 clones tested, expressed CD28, the ligand for B7. In addition, anti-CD28
      monoclonal antibody inhibited the induction of Th1 cell anergy when added to
      cultures of Th1 cells and Ag-pulsed fixed antigen-presenting cells. Taken
      together, the results indicate that B cells, even when activated, do not satisfy
      the costimulatory requirements of the Th1 cells used here, and therefore can
      present Ag in a tolerogenic fashion to Th1 cells. The costimulator deficiency of
      activated B cells may reflect an inadequacy in the level of B7 expressed or a
      lack of some other molecule.

PMID- 7505800
TI  - Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14.
AB  - CD14 is a 55-kD protein found as a glycosylphosphatidylinositol (GPI)-anchored
      protein on the surface of monocytes, macrophages, and polymorphonuclear
      leukocytes, and as a soluble protein in the blood. Both forms of CD14 participate
      in the serum-dependent responses of cells to bacterial lipopolysaccharide (LPS).
      While CD14 has been described as a receptor for complexes of LPS with LPS-binding
      protein (LBP), there has been no direct evidence showing whether a ternary
      complex of LPS, LBP, and CD14 is formed, or whether CD14 binds LPS directly.
      Using nondenaturing polyacrylamide gel electrophoresis (native PAGE), we show
      that recombinant soluble CD14 (rsCD14) binds LPS in the absence of LBP or other
      proteins. Binding of LPS to CD14 is stable and of low stoichiometry (one or two
      molecules of LPS per rsCD14). Recombinant LBP (rLBP) does not form detectable
      ternary complexes with rsCD14 and LPS, but it does accelerate the binding of LPS
      to rsCD14. rLBP facilitates the interaction of LPS with rsCD14 at
      substoichiometric concentrations, suggesting that LBP functions catalytically, as
      a lipid transfer protein. Complexes of LPS and rsCD14 formed in the absence of
      LBP or other serum proteins strongly stimulate integrin function on PMN and
      expression of E-selectin on endothelial cells, demonstrating that LBP is not
      necessary for CD14-dependent stimulation of cells. These results suggest that
      CD14 acts as a soluble and cell surface receptor for LPS, and that LBP may
      function primarily to accelerate the binding of LPS to CD14.

PMID- 7505801
TI  - Structural requirements for binding of an immunodominant myelin basic protein
      peptide to DR2 isotypes and for its recognition by human T cell clones.
AB  - Immunodominant T cell epitopes of myelin basic protein (MBP) may be target
      antigens for major histocompatibility complex class II-restricted, autoreactive T
      cells in multiple sclerosis (MS). Since susceptibility to MS is associated with
      the DR2 haplotype, the binding and presentation of the immunodominant MBP(84-102)
      peptide by DR2 antigens were examined. The immunodominant MBP(84-102) peptide was
      found to bind with high affinity to DRB1*1501 and DRB5*0101 molecules of the
      disease-associated DR2 haplotype. Overlapping but distinct peptide segments were
      critical for binding to these molecules; hydrophobic residues (Val189 and Phe92)
      in the MBP(88-95) segment were critical for peptide binding to DRB1*1501
      molecules, whereas hydrophobic and charged residues (Phe92, Lys93) in the MBP(89
      101/102) sequence contributed to DRB5*0101 binding. The different registers for
      peptide binding made different peptide side chains available for interaction with
      the T cell receptor. Although the peptide was bound with high affinity by both
      DRB1 and DRB5 molecules, only DRB1 (DRB1*1501 and 1602) but not DRB5 molecules
      served as restriction elements for a panel of T cell clones generated from two MS
      patients suggesting that the complex of MBP(84-102) and DRB1 molecules is more
      immunogenic for MBP reactive T cells. The minimal MBP peptide epitope for several
      T cell clones and the residues important for binding to DRB1*1501 molecules and
      for T cell stimulation have been defined.

PMID- 7505802
TI  - P-selectin and platelet-activating factor mediate initial endotoxin-induced
      neutropenia.
AB  - Polymorphonuclear neutrophil (PMN) accumulation within damaged tissues, a
      hallmark of acute inflammation, is dependent upon initial adhesion to endothelial
      cells. In vitro studies suggest that P-selectin and platelet activating factor
      (PAF) are key molecules in this process by promoting the initial adhesion of PMN
      to endothelial cells. We report in vivo studies in which intravenous
      administration of lipopolysaccharide (LPS) to anesthetized rats caused a very
      rapid onset (< 5 min) of neutropenia, in association with induction of surface
      expression of P-selectin on microvascular endothelial cells in kidney, liver and
      lung; analogous induction of P-selectin expression by cultured endothelial cells
      was observed in response to LPS stimulation in vitro. In addition, treatment with
      an antibody (Ab) to P-selectin (or use of a PAF antagonist) blocked development
      of neutropenia in vivo for at least 15 min post-LPS injection, and Ab treatment
      was shown to block PMN accumulation in tissues. These studies document roles for
      P-selectin and PAF in the early adhesion of PMN to endothelial cells in vivo.

PMID- 7505803
TI  - Interleukin 1 activates soluble guanylate cyclase in human vascular smooth muscle
      cells through a novel nitric oxide-independent pathway.
AB  - Recent demonstration of cytokine-inducible production of nitric oxide (NO) in
      vascular smooth muscle cells (VSMC) from rat aorta has implicated VSMC-derived NO
      as a key mediator of hypotension in septic shock. Our studies to determine
      whether an inducible NO pathway exists in human VSMC have revealed a novel
      cytokine-inducible, NO-independent pathway of guanylate cyclase activation in
      VSMC from human saphenous vein (HSVSMC). Interleukin 1 (IL-1), tumor necrosis
      factor (TNF), interferon gamma (IFN-gamma) and Escherichia coli
      lipopolysaccharide (LPS) increased cGMP at 24 h, whereas IL-2 and IL-6 were
      ineffective. The effect of IL-1 on cyclic guanosine 3',5'-monophosphate (cGMP)
      was delayed, occurring after 6 h of exposure, and was maximal after 10 h.
      Methylene blue and LY83583 reversed the IL-1-induced increase in cGMP, suggesting
      that it was mediated by activation of soluble guanylate cyclase. However, IL-1
      induced cGMP in HSVSMC was not inhibited by extracellular hemoglobin. Also, the
      effect of IL-1 on cGMP was not reversed by nitro- or methyl-substituted L
      arginine analogs, aminoguanidine, or diphenyleneiodonium, all of which inhibit IL
      1-induced NO synthase in rat aortic VSMC (RAVSMC). IL-1-induced cGMP in HSVSMC
      was also independent of tetrahydrobiopterin and extracellular L-arginine, as it
      was not affected by 2,4-diamino-6-hydroxyprytimidine, an inhibitor of
      tetrahydrobiopterin biosynthesis, and was similar in L-arginine-free and L
      arginine-containing media. Analysis of NO synthase mRNA with the use of
      polymerase chain reaction indicates that levels of mRNA for inducible NO synthase
      are several orders of magnitude lower in IL-1-treated human HSVSMC than in IL-1
      treated RAVSMC. IL-1-induced cGMP was also NO independent in human umbilical
      artery VSMC, and NO dependent in rat vena cava VSMC. Together these results
      indicate that IL-1 activates a novel NO-independent pathway of soluble guanylate
      cyclase activation in human VSMC.

PMID- 7505804
TI  - Calcium-activated potassium channels in resting and activated human T
      lymphocytes. Expression levels, calcium dependence, ion selectivity, and
      pharmacology.
AB  - Ca(2+)-activated K+[K(Ca)] channels in resting and activated human peripheral
      blood T lymphocytes were characterized using simultaneous patch-clamp recording
      and fura-2 monitoring of cytosolic Ca2+ concentration, [Ca2+]i. Whole-cell
      experiments, using EGTA-buffered pipette solutions to raise [Ca2+]i to 1 microM,
      revealed a 25-fold increase in the number of conducting K(Ca) channels per cell,
      from an average of 20 in resting T cells to > 500 channels per cell in T cell
      blasts after mitogenic activation. The opening of K(Ca) channels in both whole
      cell and inside-out patch experiments was highly sensitive to [Ca2+]i (Hill
      coefficient of 4, with a midpoint of approximately 300 nM). At optimal [Ca2+]i,
      the open probability of a K(Ca) channel was 0.3-0.5. K(Ca) channels showed little
      or no voltage dependence from -100 to 0 mV. Single-channel I-V curves were linear
      with a unitary conductance of 11 pS in normal Ringer and exhibited modest inward
      rectification with a unitary conductance of approximately 35 pS in symmetrical
      160 mM K+. Permeability ratios, relative to K+, determined from reversal
      potential measurements were: K+ (1.0) > Rb+ (0.96) > NH4+ (0.17) > Cs+ (0.07).
      Slope conductance ratios were: NH4+ (1.2) > K+ (1.0) > Rb+ (0.6) > Cs+ (0.10).
      Extracellular Cs+ or Ba2+ each induced voltage-dependent block of K(Ca) channels,
      with block increasing at hyperpolarizing potentials in a manner suggesting a site
      of block 75% across the membrane field from the outside. K(Ca) channels were
      blocked by tetraethylammonium (TEA) applied externally (Kd = 40 mM), but were
      unaffected by 10 mM TEA applied inside by pipette perfusion. K(Ca) channels were
      blocked by charybdotoxin (CTX) with a half-blocking dose of 3-4 nM, but were
      resistant to block by noxiustoxin (NTX) at 1-100 nM. Unlike K(Ca) channels in
      Jurkat T cells, the K(Ca) channels of normal resting or activated T cells were
      not blocked by apamin. We conclude that while K(Ca) and voltage-gated K+ channels
      in the same cells share similarities in ion permeation, Cs+ and Ba2+ block, and
      sensitivity to CTX, the underlying proteins differ in structural characteristics
      that determine channel gating and block by NTX and TEA.

PMID- 7505805
TI  - Advanced seminoma: treatment results, survival, and prognostic factors in 142
      patients.
AB  - PURPOSE: To investigate the efficacy of chemotherapy and to assess the
      relationship between selected pretreatment characteristics and survival in
      patients with advanced seminoma. PATIENTS AND METHODS: One hundred forty-two
      patients with advanced seminoma treated with platinum-based chemotherapy were the
      subject of this study. Treatment regimens included cisplatin, vinblastine,
      bleomycin, cyclophosphamide, and dactinomycin (VAB-6) (45 patients), a six-cycle
      regimen of VAB-6 alternating with etoposide and cisplatin (two patients),
      cisplatin and etoposide (60 patients), and etoposide and carboplatin (35
      patients). RESULTS: One hundred thirty of 140 (93%) assessable patients treated
      with platinum-based therapy achieved a favorable response (complete response or a
      partial response with negative serum tumor markers). One hundred twenty-five
      patients (88%) are alive and 120 (86%) remain progression-free at a median follow
      up duration of 43 months. Fifty-seven of 60 patients (95%) who were treated with
      cisplatin and etoposide achieved a favorable response; 55 (92%) remain
      progression-free. The relative risks of death or of an event (death or relapse)
      related to human chorionic gonadotropin (HCG) elevation were 1.8 (P = .04) and
      1.96 (P = .001), respectively. The relative risks of death or of an event
      associated with lactate dehydrogenase (LDH) elevation were 2.6 (P = .05) and 2.7
      (P = .02), respectively. All 19 patients with a mediastinal primary tumor site
      achieved a complete response, and 18 of 19 (95%) remain progression-free.
      CONCLUSION: Four cycles of cisplatin and etoposide is highly effective therapy
      for seminoma and is the standard therapy at our center. Elevation of the serum
      markers HCG and LDH were of prognostic significance, while an extragonadal
      primary tumor site was not associated with an adverse prognosis. Studies of tumor
      biology, including genetic analysis, are ongoing to determine other parameters
      that may correlate with response and survival.

PMID- 7505806
TI  - Transplantation of enriched CD34-positive autologous marrow into breast cancer
      patients following high-dose chemotherapy: influence of CD34-positive peripheral
      blood progenitors and growth factors on engraftment.
AB  - PURPOSE: To evaluate the capacity of enriched CD34-positive (CD34+) progenitor
      cells to reconstitute hematopoiesis in poor-prognosis breast cancer patients
      following administration of a high-dose alkylating agent chemotherapy regimen.
      PATIENTS AND METHODS: Forty-four breast cancer patients received high-dose
      chemotherapy followed by autologous bone marrow support (ABMS) with CD34+
      hematopoietic progenitor cells in five sequentially treated cohorts. Following
      infusion of CD34+ marrow, cohort no. 1 received no growth factor, cohort no. 2
      received granulocyte colony-stimulating factor (G-CSF), and cohort no. 3 received
      granulocyte-macrophage colony-stimulating factor (GM-CSF). Cohort no. 4 received
      the CD34+ fractions of both marrow and peripheral-blood progenitor cells (PBPCs)
      plus G-CSF. Cohort no. 5 received only the CD34+ PBPCs plus G-CSF.
      Immunohistochemical staining for breast cancer was performed on all hematopoietic
      cell products before and after the positive selection procedure, to assess
      quantitatively the level of tumor-cell contamination. RESULTS: Cohorts no. 1, 2,
      3, 4, and 5 achieved a granulocyte count > or = 500 x 10(9)/L in a median of 23,
      10, 16, 11, and 11 days, with a platelet count greater than 20,000 x 10(9)/L
      documented in a median of 22, 23, 32, 12, and 10 days, respectively. The time to
      granulocyte reconstitution was significantly shorter for patients who received
      CD34+ PBPCs alone (cohort no. 5), or in combination with CD34+ marrow (cohort no.
      4), when compared with those who received only the CD34+ marrow fraction (P <
      .01). From 1 to greater than 4 logs of breast cancer cell depletion were
      documented after CD34-selection, for patients in whom tumor was initially
      detected. CONCLUSION: CD34+ marrow and/or PBPCs provide reliable and timely
      hematopoietic reconstitution in breast cancer patients receiving high-dose
      chemotherapy. Contamination of both marrow and PBPCs with breast cancer cells was
      reduced using this positive selection technique.

PMID- 7505807
TI  - Double dose-intensive chemotherapy with autologous marrow and peripheral-blood
      progenitor-cell support for metastatic breast cancer: a feasibility study.
AB  - PURPOSE: Twenty-seven percent of responding metastatic breast cancer patients
      remain progression-free a median 29 months following one intensification course
      of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800
      mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). European
      investigators report high complete response (CR) rates with melphalan for breast
      cancer. This trial studied the feasibility of two tandem high-dose
      intensification therapies in an attempt to optimize disease response and
      duration. PATIENTS AND METHODS: Women with at least partial responses (PRs) to
      induction therapy received melphalan (140 to 180 mg/m2), followed 24 hours later
      by chemotherapy and granulocyte colony-stimulating factor (G-CSF)-mobilized
      peripheral-blood progenitor cells (PBPCs) and subsequent G-CSF until WBC
      recovery. The women were monitored as outpatients. After recovery, patients were
      hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS: Twenty women
      were assessable. Fourteen (70%) required admission for fever (10% infection) or
      mucositis (35%) after melphalan (median stay, 5 days). Median days of absolute
      neutrophil count (ANC) less than 500/microL and platelet count less than
      20,000/microL were 6 and 5.5, respectively. Patients received CTCb 25 days after
      starting melphalan and had a hospital stay of 25 days. After CTCb, median days of
      ANC less than 500/microL and platelet count less than 20,000/microL were 11.5 and
      24, respectively. Grade 3 toxicities included venoocclusive disease (VOD) (10%),
      mucositis (45%), and infection (20%). Toxicities were reversible without
      mortality. CONCLUSION: With mobilized PBPCs and growth factors, double dose
      intensive chemotherapy is feasible with acceptable toxicity. When compared with
      trials using marrow alone, these supportive adjuncts decrease sepsis and organ
      toxicity. The concepts of dose and dose-intensity may now be more effectively and
      safely studied in chemosensitive tumors, including breast cancer.

PMID- 7505808
TI  - Phase II trial of bleomycin, ifosfamide, and carboplatin in metastatic cervical
      cancer.
AB  - PURPOSE: A bleomycin, carboplatin, and ifosfamide (BIC) chemotherapy protocol was
      designed to evaluate tumor response and palliation in patients with advanced
      cervical cancer. PATIENTS AND METHODS: Forty patients with stage IV primary or
      recurrent squamous cell carcinoma of the cervix (19 previously irradiated and 21
      nonirradiated) were assigned to treatment with six cycles of BIC: bleomycin, 30
      mg bolus on day 1; carboplatin, 200 mg/m2 bolus on day 1; and ifosfamide, 2g/m2
      for 3 consecutive days, infused over 2 hours. Mesna was administered as a bolus
      15 minutes, and 4 and 8 hours after ifosfamide at 20% (intravenous [IV]), and 40%
      (orally, at home) of the ifosfamide dose, respectively. RESULTS: Thirty-five
      patients (27 stage IVA and eight stage IVB) were considered eligible for response
      and toxicity evaluation. After a median of four cycles (maximum of six in
      responders), we observed objective responses in 21 patients (60%), with eight
      complete responses (CRs; 23%), including two histologically documented by
      laparotomy, and 13 (37%) partial responses (PRs) (95% confidence limits, 44% to
      76%, 9% to 37%, and 21% to 53%, respectively). Median overall survival duration
      was 11 months (range, 3 to 24+). Median overall survival duration in the
      nonirradiated group was 17 months versus 4 months in the previously irradiated
      group (P = .005). The median progression-free survival duration of the responders
      was 12 months, and the median disease-free survival duration of the complete
      responders was 14 months. Toxicity was acceptable and included manageable
      alopecia, vomiting, and neutropenia. There was one toxic death due to febrile
      neutropenia and sepsis. CONCLUSION: BIC can be administered on an outpatient
      basis and seems to be effective in inducing tumor response and palliation in
      patients with disseminated squamous cell carcinoma of cervix, with a possible
      survival benefit for previously nonirradiated patients, with an acceptable
      toxicity profile.

PMID- 7505809
TI  - Received dose-intensity: a randomized trial of weekly chemotherapy with and
      without granulocyte colony-stimulating factor in small-cell lung cancer.
AB  - PURPOSE: A prospective randomized trial to determine if granulocyte colony
      stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of
      weekly chemotherapy in patients with small-cell lung cancer (SCLC). PATIENTS AND
      METHODS: Forty patients with SCLC with good prognostic features (all patients
      with limited disease [LD], and extensive-disease [ED] patients with Eastern
      Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels <
      1.5 times the upper limit of normal) were randomized to receive weekly
      chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered
      subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of
      cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days
      1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin
      25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions
      and treatment delays) were made according to defined hematologic criteria.
      RESULTS: Dose reductions were made at some point during treatment in 12 of 17
      patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20).
      The proportion of patients experiencing dose reductions due to leukopenia was
      significantly higher in the control arm (nine of 17) compared with the G-CSF arm
      (four of 23, P < .04). Cycle delays due to leukopenia were similar in both arms
      of the study. The RDI was 82% of projected in the control arm (95% confidence
      interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to
      87%) (P value not significant). CONCLUSION: In this randomized trial, G-CSF
      significantly decreased dose reductions due to neutropenia. However,
      administration of G-CSF did not decrease dose reductions or treatment delays to a
      level that would allow an increase in received dose-intensity. Nonhematologic
      toxicities such as increased creatinine concentration also prevented an increase
      in the RDI in the G-CSF arm.

PMID- 7505811
TI  - The future of dentistry.

PMID- 7505812
TI  - The future of dentistry: a clinician's perspective.

PMID- 7505810
TI  - Phase I study of irinotecan and cisplatin with granulocyte colony-stimulating
      factor support for advanced non-small-cell lung cancer.
AB  - PURPOSE: Since leukopenia was one of the dose-limiting toxicities of the
      combination of irinotecan (CPT-11) and cisplatin in a previous trial, we
      conducted a phase I trial to investigate whether support with recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) would permit further
      intensification of the CPT-11 dose in combination with a fixed cisplatin dose.
      PATIENTS AND METHODS: Twenty previously untreated patients with stage IIIB or IV
      non-small-cell lung cancer (NSCLC) were treated with CPT-11 on days 1, 8, and 15
      in combination with cisplatin 80 mg/m2 intravenously on day 1. In addition, rhG
      CSF (2 micrograms/kg/d) was administered on days 4 to 21, except on the days of
      CPT-11 treatment. The starting dose of CPT-11 was 70 mg/m2, and the CPT-11 dose
      was escalated in 10-mg/m2 increments until the maximum-tolerated dose was
      reached. RESULTS: Diarrhea was the dose-limiting toxicity at 90 mg/m2. Two of six
      patients experienced either grade 3 or 4 diarrhea or grade 3 leukopenia during
      the first course of therapy at this dose level. Modest escalation of the CPT-11
      dose from 80 to 90 mg/m2 resulted in a marked increase in the plasma
      concentration of 7-ethyl-10-hydroxycamptothecin (SN-38). Occurrence of diarrhea
      was well correlated with the peak plasma concentration (Cmax) of SN-38 (P =
      .035). There were 10 partial responses (50%) among 20 patients. CONCLUSION: The
      recommended dose for phase II studies is 80 mg/m2 of CPT-11, and 80 mg/m2 of
      cisplatin plus rhG-CSF. With the use of rhG-CSF, the CPT-11 dose can be increased
      33% above that in the original regimen (60 mg/m2 of CPT-11 and 80 mg/m2 of
      cisplatin).

PMID- 7505814
TI  - Alternative payment plans.

PMID- 7505813
TI  - The dental facility of the future.

PMID- 7505815
TI  - Computers, the future and you.
AB  - Computers are no longer like rocket ships: complicated, expensive and requiring a
      "rocket scientist" to operate. Computers are now like telephones: you can
      practice without them, but do you really want to?

PMID- 7505816
TI  - Dentistry in the decade ahead.

PMID- 7505817
TI  - A quick triple.

PMID- 7505818
TI  - Lack of correlation between tritiated deoxyglucose, thallium-201 and technetium
      99m-MIBI cell incorporation under various cell stresses.
AB  - The use of fluorodeoxyglucose (FDG) and PET, recognized as an accurate tool for
      the specific diagnosis and staging of cancer, is currently being tested to
      monitor cancer therapy. Similar investigations have been performed with the
      nonPET markers 201Tl and 99mTc-methoxyisobutylisonitrile (MIBI), two markers of
      myocardial perfusion shown to concentrate in malignant cells. We have tested the
      hypothesis that the cellular incorporation of 201Tl and 99mTc-MIBI reflects that
      of FDG and correlates with treatment efficacy. METHODS: We measured the
      incorporation in U937 cells of tritiated deoxyglucose (3H-DG), 201Tl and 99mTc
      MIBI in basal conditions after stimulation or inhibition of the glucose metabolic
      pathway and after exposure to toxic agents selected to mimic the effects of
      chemotherapy. Thallium-201 or 99mTc-MIBI cell incorporation remained at basal
      levels after exposure to insulin, whereas 3H-DG cell incorporation was greatly
      enhanced. Conversely, in the presence of 50 microM of NaF for 3 hr, only 3H-DG
      cell incorporation was reduced to 57.2% +/- 6.2% from control conditions.
      Cycloheximide (CYX), metaiodobenzylguanidine (MIBG) and bleomycin (BLM) were
      added to cell cultures. RESULTS: Neither 201Tl nor 99mTc-MIBI followed the
      changes in cell incorporation observed with 3H-DG. In addition, only 3H-DG cell
      incorporation was inversely correlated to the time of cell exposure or to the
      cell culture concentration of MIBG and BLM. CONCLUSION: In this model, cell
      incorporation of 201Tl or 99mTc-MIBI differed from cell incorporation of 3H-DG
      suggesting that it was not directly related to cell glycolysis activity and cell
      injury. In conclusion, these results do not support the hypothesis that 201Tl or
      99mTc-MIBI could replace FDG to monitor cancer treatment.

PMID- 7505820
TI  - Distribution of disulfonated and tetrasulfonated aluminum phthalocyanine between
      malignant and host cell populations of a murine fibrosarcoma.
AB  - Levels of disulfonated and tetrasulfonated aluminum phthalocyanines (AlPcS2,4)
      were measured in cells derived from FsaR tumors (murine fibrosarcoma) using a
      fluorescence-activated cell sorter (FACS). The tumors were excised from animals
      injected with the sensitizer 24 h earlier and enzymatically dissociated. Before
      flow cytometry, the cells were stained with fluorescein isothiocyanate-conjugated
      anti-mouse monoclonal antibodies to specific immune cell membrane markers (Mac1,
      Fc receptor (FcR) or CD45). Staining to FcR and CD45 was combined with a DNA
      stain Hoechst 33342. This enabled concomitant discrimination to be made by the
      FACS between different populations of tumor-infiltrating host cells and malignant
      cells. The results showed on average 1.49 times higher AlPcS2 levels and 1.16
      times higher AlPcS4 levels in Mac1-positive (Mac1+) compared with Mac1-negative
      (Mac1-) tumor cell populations. The same type of experiments performed with
      SCCVII tumor (squamous cell carcinoma) gave average Mac1+/Mac1- ratios of 1.75
      and 1.45 for AlPcS2 and AlPcS4 respectively. The data using other antibodies and
      DNA staining are consistent with the conclusion that, based on average per cell
      content, elevated levels of AlPcS2, and to a lesser extent AlPcS4, are retained
      in tumor-associated macrophages (TAM). The levels of these photosensitizers in
      other leukocytes and in non-immune host cells were not substantially different
      from those in malignant tumor cells. It is also shown that elevated levels of
      AlPcS2 and AlPcS4 are not localized in all TAM, but rather in a fraction of this
      cell population characterized by extremely high photosensitizer content.

PMID- 7505819
TI  - Dosimetry and toxicity of samarium-153-EDTMP administered for bone pain due to
      skeletal metastases.
AB  - Palliation of bone pain in patients with cancer metastatic to bone is being
      evaluated in several cancer centers by the administration of the bone-seeking
      phosphonate ethylenediaminetetramethylenephosphonic acid (EDTMP) chelated with
      the beta particle-emitting radionuclide 153Sm. METHODS: In this study, 153Sm
      EDTMP was intravenously injected into 19 patients over a 1-min period. Patients
      received up to four injections of 18.5 MBq (0.5 mCi) or 37 MBq (1.0 mCi) per
      kilogram of body weight. Skeletal retention was calculated from urinary
      excretion. RESULTS: No uptake of 153Sm-EDTMP in nonskeletal tissues was observed
      in whole-body gamma camera images. The mean skeletal uptake for all patients was
      54% +/- 16% of the injected dose (%ID). This resulted in the bone marrow
      receiving 89 cGy/GBq +/- 27 cGy/GBq (3.28 cGy/mCi +/- 0.99 cGy/mCi), with
      calculated marrow doses ranging from 27 cGy to 338 cGy. For each patient, the
      estimated radiation absorbed dose to the marrow was correlated to the percent
      decrease in platelet number, ranging from 7.4% to 78.9%. CONCLUSION: Since the
      deviation of uptake between the four injections for a given patient (7.6% ID) was
      less than the deviation for all patients (16% ID), the initial dose may be used
      to estimate the skeletal uptake for the remaining doses. These radiation dose
      estimates permit patients at risk to be identified prior to reaching
      myelotoxicity and develop dose-response models. Thirteen patients (68%) reported
      significant pain relief from this radionuclide therapy. Bone pain appears to be
      alleviated by 153Sm-EDTMP with limited red marrow doses and no toxic effects in
      other organs.

PMID- 7505821
TI  - Whipple's disease: the bacillus unmasked.

PMID- 7505822
TI  - Heterogeneity of the early outward current in ventricular cells isolated from
      normal and hypertrophied rat hearts.
AB  - 1. The nature, magnitude and kinetics of the 4-aminopyridine-sensitive early
      outward current (Ito) were analysed in isolated ventricular myocytes from the
      septum, the apex and the left ventricular free wall of rat ventricles using the
      whole-cell voltage clamp method. The modulatory effect of pressure overload
      induced cardiac hypertrophy on the regional variations of Ito was assessed in
      each topographical class of cells. 2. Voltage clamp experiments were performed at
      room temperature (20-25 degrees C) in the absence of Na+ on both sides of the
      membrane and in the presence of 3 mM CoCl2. Ito was studied from a holding
      potential of -80 mV and determined by subtraction of total outward currents
      elicited by the same protocols in the presence of 3 mM 4-aminopyridine (4-AP)
      from those obtained in its absence. 3. In normal hearts, membrane passive
      properties were very similar in each topographical class of cells. Our results
      confirmed that the predominant early outward current in rat ventricular cells was
      4-AP-sensitive, time and voltage dependent, and demonstrated that the magnitude
      of the current varied on a regional basis: current density of Ito in left
      ventricular free wall cells (30.1 +/- 9.2 pA/pF at +60 mV) was larger than in
      apex cells (20.2 +/- 1.7 pA/pF) or in septum cells (11.9 +/- 3.3 pA/pF). We
      noticed a larger variability in data from left ventricular free wall compared
      with other regions. 4. No shift in steady-state voltage dependence of Ito
      activation and inactivation was found. However, the maximal computed chord
      conductances were (in microS/pF): 0.18 +/- 0.07 for left ventricular free wall
      cells, 0.13 +/- 0.02 for apex cells, and 0.08 +/- 0.02 for septum cells. These
      findings might reflect a differential distribution in functional channel
      densities. 5. No difference in voltage-dependent Ito activation kinetics was
      present with respect to topography. However, inactivation time constants in
      septum were longer than those of both other groups. 6. Left ventricular
      hypertrophy was induced by abdominal aortic constriction and its effects compared
      to the findings from normal rats. Hypertrophied cells had similar resting
      potentials but higher capacitance values than normal cells. Although Ito
      magnitude appeared not to be modified, the current density-voltage curves were
      slightly shifted to more positive potentials and significantly decreased as
      compared to normal cells (in pA/pF, at +60 mV): 8.4 +/- 5.0 in the left free wall
      group, 11.6 +/- 2.0 in the apex group, and 3.8 +/- 1.5 in the septum
      group.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7505823
TI  - Two kinetically distinct components of hyperpolarization-activated current in rat
      superior colliculus-projecting neurons.
AB  - 1. Whole-cell and perforated patch recording techniques were used to examine the
      activation, deactivation and inactivation of the time-dependent hyperpolarization
      activated inward currents (Ih) in isolated superior colliculus-projecting (SCP)
      neurons from rat primary visual cortex. 2. Examination of inward current
      waveforms revealed the presence of two kinetically distinct components of Ih: one
      that activates with a time constant of the order of hundreds of milliseconds, and
      one that activates with a time constant of the order of seconds. We have termed
      these Ih,f and Ih,s, to denote the fast and slow components, respectively, of
      current activation. The time constants of activation of both Ih,f and Ih,s
      decrease with increasing membrane hyperpolarization. 3. Following the onset of
      hyperpolarizing voltage steps, a delay is evident prior to time-dependent inward
      current activation. This delay is voltage dependent and decreases with increasing
      membrane hyperpolarization. 4. The sigmoidal inward current waveforms are well
      fitted by the sum of two exponentials in which the faster term, corresponding to
      the activation of Ih,f, is raised to the power 1.34 +/- 0.26 (mean +/- S.D.). The
      non-integral exponent suggests that Ih,f activation involves at least two
      energetically non-equivalent gating transitions prior to channel opening. 5. Over
      a limited voltage range, tail currents could also be resolved into two distinct
      components. The faster component, which corresponds to the deactivation of Ih,f,
      decayed over a single exponential time course with a mean (+/- S.D.) time
      constant of 355 +/- 161 ms at -70 mV. Ih,s decay also followed a single
      exponential time course with a mean (+/- S.D.) time constant of 2428 +/- 1285 ms
      at -70 mV. Both deactivation time constants decreased with increasing
      depolarization. 6. The separation of inward current activation and deactivation
      into two distinct components and the lack of correlation between the relative
      amplitudes of these components suggest that Ih,f and Ih,s reflect the presence of
      two functionally distinct channel populations. 7. No decrements in time-dependent
      hyperpolarization-activated inward currents were observed during
      hyperpolarizations lasting up to 18 s, suggesting that neither Ih,f nor Ih,s
      inactivates from the open state. In addition, 10 s depolarizations to 0 mV prior
      to activation did not alter the waveforms of the inward currents activated
      directly from -40 mV, suggesting that Ih,f and Ih,s also do not inactivate from
      closed states. 8. The hyperpolarization-activated currents in rat SCP neurons are
      ideally suited to contribute to the control of the resting membrane potential and
      input resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7505824
TI  - An ionic current model for neurons in the rat medial nucleus tractus solitarii
      receiving sensory afferent input.
AB  - 1. Neurons from a horizontal slice of adult rat brainstem were examined using
      intracellular recording techniques. Investigations were restricted to a region
      within the nucleus tractus solitarii, medial to the solitary tract and centred on
      the obex (mNTS). Previous work has shown this restricted area of the NTS to
      contain the greatest concentration of aortic afferent baroreceptor terminal
      fields. Electrical stimulation of the tract elicited short-latency excitatory
      postsynaptic potentials in all neurons. 2. mNTS neurons were spontaneously active
      with firing frequencies ranging between 1 and 10 Hz, at resting potentials of -65
      to -45 mV. These neurons did not exhibit spontaneous bursting activity. 3.
      Depolarizing current injection immediately evoked a finite, high-frequency spike
      discharge which rapidly declined to a lower steady-state level (i.e. spike
      frequency adaptation, SFA). Increasing depolarizations produced a marked increase
      in the peak instantaneous frequency but a much smaller increase in the steady
      state firing level. 4. Conditioning with a hyperpolarizing prepulse resulted in a
      prolonged delay of up to 600 ms before the first action potential (i.e. delayed
      excitation, DE) with an attendant decrease in peak discharge rates. DE was
      modulated by both the magnitude and duration of the prestimulus
      hyperpolarization, as well as the magnitude of the depolarizing stimulus.
      Tetrodotoxin (TTX) eliminated spike discharge but had little effect on the ramp
      like membrane depolarization characteristic of DE. 5. We have developed a
      mathematical model for mNTS neurons to facilitate our understanding of the
      interplay between the underlying ionic currents. It consists of a comprehensive
      membrane model of the Hodgkin-Huxley type coupled with a fluid compartment model
      describing cytoplasmic [Ca2+]i homeostasis. 6. The model suggests that (a) SFA is
      caused by an increase in [Ca2+]i which activates the outward K+ current, IK,Ca,
      and (b) DE results from the competitive interaction between the injected
      depolarizing current and the hyperpolarization-activated transient outward K+
      currents, IA and ID. 7. We conclude that our ionic current model is capable of
      providing biophysical explanations for a number of phenomena associated with
      brainstem neurons, either during spontaneous activity or in response to patterned
      injections of current. This model is a potentially useful adjunct for on-going
      research into the central mechanisms involved in the regulation of both blood
      pressure and ventilation.

PMID- 7505825
TI  - Brief calcium transients evoked by glutamate receptor agonists in rat dorsal horn
      neurons: fast kinetics and mechanisms.
AB  - 1. The calcium indicator dye, indo-1, was used to analyse the receptor-specific
      mechanisms of intracellular calcium ion ([Ca2+]i) responses evoked by excitatory
      amino acid (EAA) stimulation of dorsal horn neurons. Measurements of somal
      changes in [Ca2+]i were made on a subsecond time scale under conditions designed
      to allow membrane potential to mediate interactions between agonist-gated
      channels and voltage-gated calcium channels (VGCCs). 2. Voltage-gated calcium
      channels were activated in a receptor-independent manner using elevated
      extracellular [K+]. The concentration-dependence of K(+)-evoked [Ca2+]i
      transients was steep and variable among cells, with a mean maximal [Ca2+]i
      response of 1400 nM and a rapid maximal rate of rise. These data indicate that
      VGCCs provide a high-capacity route for Ca2+ entry that is very sensitive to
      small changes in membrane potential. 3. Stimulation of non-NMDA receptors using
      the non-desensitizing agonist kainate also evoked large [Ca2+]i responses (mean,
      840 nM) that were predominantly due to indirect activation of VGCCs. However, in
      60% of neurons tested, a component of the [Ca2+]i transient evoked by kainate at
      concentrations above 10 microM was not blocked by the potent VGCC blocker,
      lanthanum (La3+). The La(3+)-resistant [Ca2+]i responses to kainate rose
      exponentially, required extracellular Ca2+, and were caused neither by evoked
      release of EAA transmitters nor by reversal of Na(+)-Ca2+ exchange. These
      responses may be mediated by a Ca(2+)-permeable conformation of non-NMDA
      receptors and can also be evoked by quisqualate, (S)-alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionic acid (AMPA) and glutamate. 4. Non-NMDA receptors
      were activated in a desensitizing manner using quisqualate or AMPA. Quisqualate
      evoked small [Ca2+]i transients (210 nM) with a slow rate of rise. Typically,
      above 3 microM quisqualate, the size of the responses decreased, reflecting
      desensitization of the receptor. Responses to quisqualate were blocked by removal
      of extracellular Ca2+ indicating that mobilization of intracellular Ca2+ stores
      does not occur in the majority of dorsal horn neurons. However, trans-(+-)-1
      amino-1,3-cyclopentane dicarboxylic acid (trans-ACPD) was occasionally able to
      evoke modest Ca2+ release. 5. Activation of the Ca(2+)-permeable NMDA receptors
      evoked [Ca2+]i transients that were large (780 nM), with a moderate rate of rise,
      and that generally achieved a maximum amplitude at NMDA concentrations around 300
      microM. 6. Glutamate was used to examine [Ca2+]i responses to the activation of
      mixed EAA receptor subtypes by an endogenous ligand.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7505826
TI  - Functional coupling between the active transport of glucose and the secretion of
      intestinal neurotensin in rats.
AB  - 1. In this study, the mechanisms involved in the release of neurotensin-like
      immunoreactivity (NTLI) by glucose were investigated with the isolated,
      vascularly perfused rat jejunoileum preparation. 2. Luminal infusion of glucose
      (1-250 mM) produced a sharp and sustained release of NTLI in the intestinal
      venous effluent. The first significant response was observed with 5 mM glucose
      and the release reached a maximum under 250 mM glucose with a plateau secretion
      at 500% of basal. 3. There was no significant difference in the ability of
      galactose and 3-O-methylglucose to release NTLI when compared to glucose, but
      alpha-methylglucose, mannose, 2-deoxyglucose and fructose did not stimulate NTLI
      release. 4. Luminal infusion of 5 mM phloridzin reduced the glucose-induced
      release of NTLI by 90%. Intra-arterial infusion of glucose (25 mM) or of
      phloretin (20 microM) had no significant effect on the glucose-evoked NTLI
      secretion. 5. Intra-arterial infusion of ouabain (1 mM) produced a dramatic
      increase (at about 1500% of basal) in portal NTLI although it drastically reduced
      intestinal absorption of glucose. 6. Intra-arterial infusion of tetrodotoxin (1
      microM), atropine (10 microM), verapamil (50 microM) or nifedipine (50 microM)
      did not modify the glucose-induced NTLI secretion. 7. Intra-arterial infusion of
      forskolin (2-20 microM) evoked a prompt and well-sustained secretion of NTLI
      which was increased to a mean value of 800% of basal with the highest dose
      tested. 3-Isobutyl-1-methylxanthine (IBMX, 10-100 microM) also stimulated the
      secretion of NTLI (maximal increase at 725% of basal at 100 microM). In contrast,
      intra-arterial infusion of 4-beta-phorbol 12-myristate, 13-acetate (PMA, 0.05-0.5
      microM) had no effect on NTLI release. 8. IBMX (10-100 microM) synergistically
      enhanced NTLI responses induced by 250 mM glucose; the integrated response of
      NTLI release was 3- to 5-fold higher than the sum of individual responses
      produced by the same stimulants given separately. 9. It is concluded that the
      carbohydrate-induced NTLI release is related to the active, sodium-dependent
      hexose transport, but not to the carbohydrate catabolic pathway. Furthermore, the
      intramural nerves and L-type calcium channels are not involved in the glucose
      induced NTLI secretion. Finally, the secretory activity of the intestinal N cell
      seems to be mainly stimulated through a cAMP-dependent pathway.

PMID- 7505827
TI  - Pharmacology of the SV channel in the vacuolar membrane of Chenopodium rubrum
      suspension cells.
AB  - Single channel performance and deactivation currents have been analyzed in the
      presence of cation channel blockers to reveal pharmacological properties of the
      slow-activating (SV) cation-selective ion channel in the vacuolar membrane
      (tonoplast) isolated from suspension cells of Chenopodium rubrum L. At a holding
      potential of -100 mV, the SV channel showed half-maximal inhibition with 20 mM
      tetraethylammonium (TEA), 7 microM 9-amino-acridine, 6 microM (+)-tubocurarine,
      300 nM quinacrine, and 35 microM quinine, respectively. The SV channel is also
      blocked by charybdotoxin (20 nM at -80 mV) but not by apamine. 9-Amino-acridine,
      (+)-tubocurarine and quinacrine act in a voltage-dependent fashion, binding to
      the open channel and to different sites along the transmembrane voltage profile
      according to Woodhull (J. Gen. Physiol. 61:687-708, 1973). No binding site could
      be specified for charybdotoxin, which binds to the closed channel, and for
      quinine. Except for quinine, all tested blockers were effective only if added to
      the cytoplasmic side of the tonoplast. A structural relationship between the SV
      channel and Maxi-K channels in animal systems is inferred.

PMID- 7505828
TI  - Ion channel properties and episodic activity in isolated immortalized
      gonadotropin-releasing hormone (GnRH) neurons.
AB  - The mechanism of periodic gonadotropin-releasing hormone (GnRH) secretion from
      hypothalamic neurons is difficult to elucidate due to the diffuse distribution of
      GnRH neurons and the complex interaction of neuronal inputs onto them. Recent use
      of transgenic techniques allowed construction of an immortalized GnRH neuronal
      cell line (GT1), which has neuronal markers and secretes GnRH in a periodic
      fashion. Using the patch-clamp recording technique in the whole-cell and nystatin
      perforated-patch configuration, the present experiments show that this cell line
      expressed a tetrodotoxin-sensitive Na channel, two types of Ca channels, three
      types of outward K channels and a K inward rectifier. The latter current was
      suppressed in some cells by GnRH or somatostatin. In addition, a gamma
      aminobutyric acid (GABA) response, presumably through GABAA receptors, is
      recorded. In long-term current-clamp recordings, spontaneous depolarizing
      activity was found to increase, and then decrease, between 20-35 min after
      removal of the cells from serum- and steroid-containing medium. In some cases,
      more than one cycle of activity was seen. Under voltage clamp, an inward current
      was recorded at similar times, with reversal at about -15 mV. Thus, two
      mechanisms of cell interaction, GABAA responses and feedback through GnRH
      responses, and one mechanism of endogenous periodic electrical activity were
      observed in these cells, which could synchronize periodic GnRH release.

PMID- 7505830
TI  - Dose-intense taxol: high response rate in patients with platinum-resistant
      recurrent ovarian cancer.
AB  - BACKGROUND: Paclitaxel (Taxol), a diterpene plant product that promotes tubulin
      polymerization, has documented activity against a number of solid tumors,
      including ovarian cancer and breast cancer. PURPOSE: Our purpose was to conduct a
      phase II clinical trial investigating the response of patients with advanced
      recurrent ovarian carcinoma to high-dose paclitaxel combined with granulocyte
      colony-stimulating factor (G-CSF). METHODS: A prospective phase II clinical trial
      of patients with advanced-stage, recurrent ovarian cancer was undertaken.
      Patients received 250 mg/m2 paclitaxel every 21 days; cycles were given on a
      rigid schedule; delays were permitted only for extreme circumstances. G-CSF at a
      dose of 10 micrograms/kg per day was given to ameliorate myelo-suppression. If a
      patient showed fever and neutropenia, G-CSF dosage was increased to 20
      micrograms/kg per day so that paclitaxel dose intensity could be maintained.
      Patients were assessed for response every two cycles, and those with complete
      radiographic resolution of disease underwent peritoneoscopy. RESULTS: Forty-four
      patients were assessable for response. Twenty-one had a reduction in tumor volume
      greater than 50%, yielding an objective response rate of 48% (21 of 44 patients;
      95% confidence interval, 32%-63%). Six (14%) of the 44 patients had complete
      radiographic resolution of disease; two of the six also had negative biopsy
      specimens and washings at peritoneoscopy. Age, number of prior regimens, and
      clinical platinum resistance did not influence response rate or ability to
      maintain dose intensity. Dose intensity was maintained at the targeted level for
      up to 14 consecutive cycles of therapy. CONCLUSIONS: We observed a 48% response
      rate with dose-intense paclitaxel for patients with advanced-stage, platinum
      resistant, recurrent ovarian cancer. The response rate is higher than previously
      reported for paclitaxel at a lower dose in similar cohorts of patients treated
      without G-CSF. Comparison of phase II studies of paclitaxel suggests a dose
      response relationship. Therapy with dose-intense paclitaxel and G-CSF should be
      considered for patients with advanced, platinum-refractory ovarian cancer.

PMID- 7505831
TI  - Cost-effectiveness of home/hospice palliative and supportive care.

PMID- 7505829
TI  - Ca2+ activation and pH dependence of a maxi K+ channel from rabbit distal colon
      epithelium.
AB  - To determine if their properties are consistent with a role in regulation of
      transepithelial transport, Ca(2+)-activated K+ channels from the basolateral
      plasma membrane of the surface cells in the distal colon have been characterized
      by single channel analysis after fusion of vesicles with planar lipid bilayers. A
      Ca(2+)-activated K+ channel with a single channel conductance of 275 pS was
      predominant. The sensitivity to Ca2+ was strongly dependent on the membrane
      potential and on the pH. At a neutral pH, the K0.5 for Ca2+ was raised from 20 nM
      at a potential of 0 mV to 300 nM at -40 mV. A decrease in pH at the cytoplasmic
      face of the K+ channel reduced the Ca2+ sensitivity dramatically. A loss of the
      high sensitivity to Ca2+ was also observed after incubation with MgCl2, possibly
      a result of dephosphorylation of the channels by endogenous phosphatases.
      Modification of the channel protein may thus explain the variation in Ca2+
      sensitivity between studies on K+ channels from the same tissue. High affinity
      inhibition (K0.5 = 10 nM) by charybdotoxin of the Ca(2+)-activated K+ channel
      from the extracellular face could be lifted by an outward flux of K+ through the
      channel. However, at the ion gradients and potentials found in the intact
      epithelium, charybdotoxin should be a useful tool for examination of the role of
      maxi K+ channels. The high sensitivity for Ca2+ and the properties of the
      activator site are in agreement with an important regulatory role for the high
      conductance K+ channel in the epithelial cells.

PMID- 7505832
TI  - Surface-epitope masking: a strategy for the development of monoclonal antibodies
      specific for molecules expressed on the cell surface.
AB  - BACKGROUND: Producing monoclonal antibodies against specific targets, including
      tumor-specific antigens, is a tedious and extremely inefficient process. PURPOSE:
      Our purpose was to determine whether DNA transfection combined with an
      immunologic masking tactic could be used to efficiently generate hybridomas that
      secrete monoclonal antibodies. The quest was for monoclonal antibodies that would
      react with molecules existing on the surface of genetically altered cells.
      METHODS: We developed a masking technique called surface-epitope masking (SEM).
      The SEM procedure involves the selective blocking of surface antigens present in
      a genetically engineered cell (referred to as a "tester") with high-titer
      polyclonal antibodies that have been produced against the untransfected parental
      cell (referred to as a "driver"). Surface-epitope-masked tester cells were
      injected into BALB/c mice; immune spleen cells then taken from these mice were
      fused with myeloma cells. RESULTS: This process resulted in the efficient
      generation of hybridomas that secreted monoclonal antibodies that reacted with
      cell-surface antigens on transfected tester cells and with additional cell types
      that expressed the same surface molecules. In one case, CREF-Trans 6 cells were
      engineered to express a typical multidrug-resistant (MDR) phenotype. Using CREF
      Trans 6:MDR cells as a tester cell line, we utilized the SEM procedure to produce
      monoclonal antibodies that displayed surface reactivity to both CREF-Trans 6:MDR
      cells and MDR human breast carcinoma (MCF7) cells. In a second case, human
      prostatic carcinoma CREF-Trans 6 cells, which were DNA transfected and derived
      from nude mouse tumors, were used as the tester cell line. The SEM procedure was
      again used to produce monoclonal antibodies. These antibodies were designed to
      and did react with: (a) tumor-associated antigens on the surface of the original
      LNCaP cell line used to obtain human prostatic carcinoma DNA, (b) primary and
      secondary nude mouse transfectants derived from tumors, and (c) two additional
      human prostatic carcinoma cell lines, DU-145 and PC-3. CONCLUSIONS: The SEM
      approach was used for the efficient and selective development of monoclonal
      antibodies that react with cell-surface molecules with both known and unknown
      functions. IMPLICATIONS: The SEM procedure should be useful in producing
      monoclonal antibodies and identifying genes associated with important cellular
      processes, including immunologic recognition, tumorigenesis, metastasis, atypical
      multidrug resistance, and autoimmune diseases.

PMID- 7505833
TI  - Nerve growth factor stimulates GAP-43 expression in PC12 cell clones
      independently of neurite outgrowth.
AB  - Expression of the growth associated protein GAP-43 (B-50, F1, neuromodulin)
      increases with the onset of neuronal development as seen by the growth of axons.
      To investigate the relationship of the signaling events leading to GAP-43
      expression and neurite outgrowth, we examined PC12 clones with different
      phenotypes. Three clones, PC12-N09, PC12-N15, and PC12-N21, responded to NGF with
      increased expression of GAP-43, but only two clones, PC12-N15 and PC12-N21,
      responded with growth of neurites. Similar increases in expression of GAP-43 were
      obtained when these clones were exposed to the phorbol ester PMA. Thus, NGF and
      PMA induced GAP-43 expression in PC12-N09 cells in the absence of neurite
      outgrowth. In contrast, all three clones, were able to respond to forskolin (FOR)
      by initiation of long neurites which had synaptophysin in the growth cones, but
      showed only low levels of GAP-43. Combined stimulation of PC12-N09 cells with FOR
      and PMA both initiated neurites and increased expression of GAP-43 as seen in
      normal PC12 cells. These results show that PC12-N09 cells, in response to either
      NGF or PMA, can express GAP-43, but without neurite outgrowth, and that all the
      PC12 clones were also able to respond to FOR with increased neurite outgrowth in
      the presence of low levels of GAP-43. The dissociation of GAP-43 expression and
      growth of neurites observed in PC12-N09 cells suggests that signaling mechanisms
      can independently regulate GAP-43 expression and neurite outgrowth during
      neuronal differentiation.

PMID- 7505835
TI  - Nitric oxide synthase in cultured endothelial cells of cerebrovascular origin:
      cytochemistry.
AB  - Cultured cells derived from the cerebromicrovasculature can be shown to contain
      the enzyme nitric oxide synthase (NOS) by NADPH diaphorase staining. NOS is
      located largely as a distinct crescent adjacent to the nuclear membrane. NOS in
      these cells appears to be associated with the microtubule and microfilament
      structures and the Golgi apparatus of the cell as opposed to being freely soluble
      in the cytoplasm or bound to the plasma membrane. Disruption of the integrity of
      these structures with colchicine or cytochalasin B causes a change in the
      subcellular localization of NOS as well as a change in the intensity of staining.

PMID- 7505834
TI  - Serotonin-containing terminals synapse on septohippocampal neurons in the rat.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] is thought to be involved in mnemonic
      functions and dysfunctions possibly by directly contacting neurons in the medial
      septal and diagonal band nuclei (i.e., the septal complex) that project to the
      hippocampal formation. However, there is no cellular substrate for this
      modulation. Thus, we examined the ultrastructure and synaptic associations of 5
      HT-containing terminals in relation to septohippocampal neurons in the septal
      complex of the rat brain. Projection neurons were identified by retrograde
      transport of wheat germ agglutinated apo-horseradish peroxidase conjugated to
      colloidal gold particles (WAHG) following an injection into the ventral
      hippocampal formation of anesthetized adult rats. After a 1 day survival,
      sections through the septal complex were labeled with antibodies to 5-HT. By
      light microscopy, numerous processes with 5-HT immunoreactivity (5-HT-I) were
      observed in close proximity to neurons containing retrogradely transported WAHG.
      By electron microscopy, 5-HT-I was found exclusively in axons and axon terminals.
      Axons were primarily unmyelinated. Terminals with 5-HT-I were 0.35-1.2 microns in
      diameter and contained numerous small, clear vesicles and 0-4 large, dense-core
      vesicles. The 5-HT-labeled terminals: 1) contacted perikarya and dendrites (220
      of 349); 2) were closely apposed to other terminals (25 of 349); or 3) had no
      neuronal contacts in the plane of section analyzed (104 of 349). The 5-HT-labeled
      terminals formed exclusively symmetric synapses on perikarya; some of these
      perikarya as well as some large dendrites similarly contacted by the 5-HT-labeled
      terminals also contained WAHG affiliated with lysosomes and multivesicular and
      "sequestration" bodies in the cytoplasm. However, the majority of terminals with
      5-HT-I formed contacts on the shafts of small unlabeled dendrites (69% of 220);
      most of these were characterized as either asymmetric synapses or appositions not
      separated by astrocytes in the plane of section analyzed. We conclude that 5-HT
      containing terminals in the rat septal complex: 1) directly modulate
      septohippocampal and other neurons through symmetric (potentially inhibitory)
      synapses on soma and proximal dendrites; and 2) form primarily asymmetric
      (potentially excitatory) synapses with distal (small) dendrites from neurons of
      unidentified origin. These findings suggest that serotonin may affect learning
      and memory through modulation of septal efferents to the hippocampal formation
      and may have direct relevance to the neuropathological basis for Alzheimer's
      disease.

PMID- 7505836
TI  - Demyelination in a transgenic mouse: a model for multiple sclerosis.
AB  - A transgenic mouse containing 70 copies (ND4) of the transgene encoding DM20, a
      myelin proteolipid protein, appeared clinically normal up to 3 months of age. By
      8-10 months, it showed tremors, unsteady gait, and died shortly thereafter. We
      concluded that the clinical symptoms correlated with demyelination based on the
      following criteria: 1) at 10 months of age only 17% of the amount of myelin
      obtained from normal mice was isolated from the ND4 mice; 2) astrogliosis, a
      prominent feature of demyelinating disease was minimal at 3 months of age but
      prominent by 10 months; 3) at the electron microscopic level disrupted myelin was
      seen at 8 months of age in the ND4 mice and ingested myelin debris was found in
      astrocytes; 4) lymphocytic infiltration in association with endothelial cells was
      observed routinely in the ND4 mice; 5) sections through optic nerves showed
      denuded and thinly myelinated axons in the 8 month old ND4 mice. Although the
      mechanism by which demyelination takes place is not fully understood,
      measurements of the amounts of PLP suggest it is down-regulated by the large
      amount of DM20. Since DM20 is a major proteolipid in the young but a minor one in
      the adult, the persistence of high levels in the adult results in improperly
      assembled myelin which is prone to disruption. Therefore demyelination in the ND4
      mouse appears to result from the persistence of immature myelin into the adult.

PMID- 7505837
TI  - Myelin-associated glycoprotein is phosphorylated by protein kinase C.
AB  - The myelin-associated glycoprotein (MAG) is a neural recognition molecule
      involved in heterophilic interactions between myelin-forming cells and neurons.
      To characterize the molecular mechanisms underlying post-translational
      modifications which may be instrumental in signal transduction following the
      recognition event, we have studied the stimuli leading to modification of 32P
      orthophosphate incorporation into MAG in cultures of oligodendrocytes or
      transformed differentiated Schwann cells. Here we show that in oligodendrocytes
      both the 67 and 72 kD isoforms of MAG were phosphorylated exclusively on serine,
      while in the transformed Schwann cells only the 67 kD isoform was found to be
      present and phosphorylated. The phorbol ester phorbol-12-myristoyl-13-acetate
      (PMA) did not affect biosynthesis of the protein backbone, but enhanced
      incorporation of phosphate by a factor of 2-3, indicating the involvement of
      protein kinase C. Exclusive phosphorylation of serine residues was also observed,
      when purified MAG was incubated with protein kinase C in the presence of [gamma
      32P]ATP. In searching for the physiological stimuli which may trigger
      phosphorylation of MAG, cultures of oligodendrocytes were exposed to
      extracellular signals, such as coculture with dorsal root ganglion and spinal
      cord neurons carrying the MAG receptor, to membrane fractions of these neurons,
      monoclonal MAG antibody 513 binding to the recognition site of MAG, or platelet
      derived growth factor. None of these additives modified the phosphorylation of
      MAG. These observations point to the possibility that phosphorylation of MAG is
      controlled by yet unknown intracellular cues rather than by extracellular signals
      interacting with cell surface receptors of oligodendrocytes.

PMID- 7505838
TI  - Transforming growth factor beta expression in reactive spinal cord microglia and
      meningeal inflammatory cells during experimental allergic neuritis.
AB  - Experimental allergic neuritis (EAN), an inflammatory demyelinating disorder of
      the peripheral nervous system, is preceded and accompanied by a massive
      microglial reaction in the spinal cord which occurs in the absence of
      inflammatory cells infiltrating the cord parenchyma. Since transforming growth
      factor beta (TGF-beta) has been shown to play a beneficial role in experimental
      autoimmune disease and might be involved in the regulation of glial activity, we
      have investigated the expression of TGF-beta in EAN spinal cord and nerve root
      tissue. Adoptive transfer EAN was induced by the injection of neurotogenic T
      cells specific for the P2 myelin protein. In normal spinal cord tissue, both TGF
      beta 1 and TGF-beta 3 mRNA were constitutively expressed at low levels. Already 3
      days following injection of P2-specific T-cells, TGF-beta 1 mRNA levels began to
      increase, peaked at day 6 at levels about tenfold above normal, and thereafter
      declined. TGF-beta 3 was induced even earlier with a sharp rise at day 3 and a
      peak fourfold above normal at day 4. In situ hybridization for TGF-beta 1
      performed on spinal cord sections 6 days after injection of cells localized TGF
      beta 1 mRNA to many nonneuronal cells with the typical morphology of microglia.
      In addition, TGF-beta 1 mRNA was observed in the meninges, and massive
      accumulation of signal was seen over inflammatory cells infiltrating the nerve
      roots. Our data indicate that TGF-beta 1 and -beta 3 are involved in regulating
      the glial response in EAN and that activated microglial cells might control their
      own activity state by expressing TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505839
TI  - Myelin gene activation: a glucose sensitive critical period in development.
AB  - Glucose deprivation was employed to model caloric undernutrition in newborn rat
      mixed glial cultures. Six day-old cultures were placed in serum-free media
      containing glucose concentrations from 0.55 mg/ml to 10 mg/ml. The expression of
      the myelin PLP, BP, and MAG genes was determined by Northern blot analysis. The
      activation of the myelin genes began at approximately 6 days in vitro (DIV), and
      a period of rapid upregulation followed through 14 DIV. The gene activity was
      directly related to the glucose concentration. The increase in glucose
      concentration from 0.55 to 1.5 mg/ml (which spans the physiological range)
      resulted in 2-3 fold increases in expression of the myelin genes, whereas further
      increases in glucose (2-10 mg/ml) produced only slight additional elevation in
      the gene activity. We used high glucose (5-6 mg/ml) as control, or low glucose
      (0.55 mg/ml) as deprived, to delineate possible critical periods of
      oligodendrocytic differentiation. Cultures were deprived for 4-day intervals,
      staggered from 6 to 22 DIV. Deprivation from 6 to 10 DIV produced an 80-90%
      suppression of the myelin gene upregulation at 22 DIV; deprivation from 10 to 14
      DIV produced 60-70% suppression; whereas deprivation from 14 to 18 DIV was fully
      recoverable by 22 DIV. These results show that mixed glial cultures model the
      developmental pattern of myelin gene expression, as well as their vulnerability.
      Furthermore, the period of rapid upregulation of the myelin genes appears to be a
      critical period in development, during which glucose deprivation irreversibly
      alters oligodendrocyte differentiation.

PMID- 7505840
TI  - Synaptic and photoreceptor components in retinal pigment epithelial cell
      transplanted retinas of Royal College of Surgeons dystrophic rats.
AB  - Plexiform layer synaptic and photoreceptor cell components were investigated in
      retinas of Royal College of Surgeons (RCS) dystrophic rats transplanted with
      normal retinal pigment epithelial (RPE) cells by immunocytochemistry using
      previously characterized monoclonal antibodies. In retinas of normal adult rats
      and RPE-cell transplanted retinas of 4 month-old RCS rats, HNK-1, a marker for a
      carbohydrate of the neural cell adhesion molecule (N-CAM), was detected
      immunocytochemically in the inner and outer plexiform layers and ganglion cell
      bodies and their axons. HNK-1 was also detected in the inner plexiform layer of
      nontreated retinas of 4 month-old RCS rats, but was reduced to scattered patches
      in the outer plexiform layer. In addition, immunoreactivity for the SVP-38
      antibody recognizing synaptophysin was found in both plexiform layers of normal
      adult rat retinas and RPE-transplanted retinas of 4 month-old RCS rats.
      Furthermore, photoreceptor cell bodies and their inner and outer segments were
      immunostained for the opsin monoclonal antibody RET-P1 in retinas of normal adult
      rats and RPE-cell transplanted retinas of 4 month-old RCS rats. However, in
      nontreated retinas of 4-month-old RCS rats, only immunostained debris material
      was detected. These results strongly suggest that normal RPE transplants not only
      rescue photoreceptor cells in RCS rats, but also maintain an essential functional
      capacity, in this case, synaptic components in the plexiform layers.

PMID- 7505841
TI  - Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune
      encephalomyelitis and cleaves myelin basic protein.
AB  - Gelatinases in inflammatory demyelinating diseases of the central nervous system
      (CNS) were studied using actively induced experimental autoimmune
      encephalomyelitis (EAE) in mice as a model system. Clinical disease scores
      correlated in time and in intensity with pathology parameters such as cytosis in
      the cerebrospinal fluid (CSF), inflammatory infiltrates, and demyelination in the
      CNS. Zymographic analysis was employed to measure gelatinases A and B in the CSF
      from individual animals. According to their apparent molecular weight (MW),
      gelatinases A and B appeared with a MW of 65 and 95 kDa, respectively. The 65 kDa
      form was present in all samples, even in those derived from non-induced animals,
      whereas the 95 kDa form was present only in samples from animals developing EAE.
      The levels of 95 and 65 kDa gelatinase correlated with the CSF cytosis. In vitro
      digestion of myelin basic protein (MBP) with gelatinase B and analysis of the
      cleavage products by protein sequence analysis pinpointed two cleavage sites in
      conserved regions of MBP. Gelatinase production within the CNS may constitute an
      important pathogenic mechanism for both the disruption of the blood-brain barrier
      and the destruction of myelin, as observed in several neuroinflammatory
      disorders.

PMID- 7505842
TI  - Analysis of the human MBP promoter in primary cultures of oligodendrocytes:
      positive and negative cis-acting elements in the proximal MBP promoter mediate
      oligodendrocyte-specific expression of MBP.
AB  - Since the regulation of myelin basic protein expression depends primarily on the
      initiation of transcription, we analyzed the 5' flanking region of the human
      myelin basic protein gene in transient transfection studies in primary cultures
      of developing oligodendrocytes. We demonstrated that 149 base pairs 5' of the
      initiation of transcription was sufficient to direct oligodendrocyte-specific
      expression of myelin basic protein. The capsite of the fusion transcript was
      identical with that of the endogenous myelin basic protein transcript, and
      chloramphenicol acetyl transferase reporter gene expression was restricted to
      oligodendrocytes in these cultures. Within this 149 base pair region, one distal,
      negative cis-acting segment, containing a consensus nuclear factor I site, and
      one proximal, positive cis-acting segment were identified. The distal segment
      behaved more negatively in Cos-7 cells than in oligodendrocytes, reducing
      expression to background levels. Furthermore, these functionally important cis
      acting segments bound oligodendrocyte nuclear proteins in a pattern differing
      from other cells, including Cos-7 cells. Interestingly, the distal segment
      increased heterologous SV40 promoter activity in oligodendrocytes but had no
      effect on the SV40 promoter in Cos-7 cells. We conclude that the functionally
      negative distal segment may mediate oligodendrocyte-specific expression of MBP by
      restricting its expression in other cells. These experiments strongly support
      using primary cultures of oligodendrocytes for analyzing the myelin-specific
      promoters.

PMID- 7505844
TI  - [Sulfated schizophyllan as a anti-HIV agent].

PMID- 7505843
TI  - Selective expression of foreign genes in glioma cells: use of the mouse myelin
      basic protein gene promoter to direct toxic gene expression.
AB  - We have previously demonstrated that retrovirus-mediated genes were transferred
      to mouse glioma cells in a meningeal gliomatosis model (Yamada et al.: Japanese
      Journal of Cancer Research 83:1244-1247, 1992). This retrovirus vector contains
      the Escherichia coli. beta-galactosidase (beta-gal) gene as a marker for
      integration of the lacZ gene, which is controlled by the SV40 early promoter. We
      investigated whether lacZ genes could be specifically controlled in mouse glioma
      cells by glial-specific promoters, including the 2.5 kb 5' flanking region of the
      mouse glial fibrillary acidic protein (GFAP) gene, the 1.3 kb 5' flanking region
      of the myelin basic protein (MBP) gene, and the 1.5 kb 5' flanking region of the
      myelin proteolipid protein (PLP) gene. Psi-2 packaging cells were transfected
      with each retrovirus vector (GFAP promoter-, MBP promoter-, and PLP promoter
      lacZ) and the infectious virus particles were recovered from the supernatants.
      Blue staining for beta-gal was detected in various fibroblast, myeloma, and
      glioma cell lines transduced with the retrovirus BAG vector. On the other hand,
      blue staining was only detected in glioma cells after transduction with the lacZ
      gene-bearing retrovirus controlled by glial-specific promoters. The strongest
      promoter activity was detected after transduction with the retrovirus in which
      the MBP promoter controlled the lacZ gene. Mouse glioma cells transduced with
      retrovirus containing the MBP promoter directing the herpes simplex virus type 1
      thymidine kinase (HTK) gene were extremely sensitive to ganciclovir, while the
      parental cells and cells transduced with retrovirus containing the lacZ gene were
      not sensitive to ganciclovir.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505845
TI  - [Inhibitory effects of human immunodeficiency virus on replication].

PMID- 7505846
TI  - [Reverse transcriptase inhibitors as anti-HIV agents].

PMID- 7505847
TI  - [HEPT and its related compounds as anti-HIV agents].

PMID- 7505848
TI  - [Detection of antibodies against HIV-1 and HIV-2 using "new antigens"].

PMID- 7505849
TI  - [AIDS therapy with reverse transcriptase inhibitors].

PMID- 7505850
TI  - [Immunotherapy for HIV carrier].

PMID- 7505851
TI  - [Anti-HIV drug development: future prospect and problems].

PMID- 7505852
TI  - [Hematological abnormalities in patients with AIDS].

PMID- 7505853
TI  - [Perinatally acquired human immunodeficiency virus infection].

PMID- 7505854
TI  - [HIV drug resistance and its genetic basis].

PMID- 7505855
TI  - Mechanics of patch clamped and intact cell-membranes in relation to SA channel
      activation.
AB  - Stretch activated (SA) channels are believed to be activated by tension in the
      membrane generated by membrane stretch. However, very few studies have been made
      on the quantitative estimation of the tension during membrane stretch. Here we
      present a method to evaluate the tension both in patch clamped and intact cell
      membranes. The tension in patch clamped membranes was calculated from Laplace's
      law by knowing transmembrane pressure and the radius of patch-curvature. We also
      provide a simpler version for calculating the tension from the pressure and
      pipette radius. The tension in intact cell membranes was calculated from Hook's
      law based on the measurement of changes in cell surface area. The estimated
      tension required for activating SA channels in both types of membranes was found
      to be comparable suggesting that the SA channel acts as a physiological
      mechanotransducer in intact cells.

PMID- 7505856
TI  - How neurotransmitters affect axoplasmic transport?
AB  - The effects of acetylcholine (ACh) and adrenaline on fast axoplasmic transport of
      cultured superior cervical ganglion cells were analyzed with a computer-assisted
      video-enhanced differential interference contrast microscopic system. ACh
      suppressed the transport reversibly in both anterograde and retrograde
      directions, and adrenaline increased the transport reversibly. These effects are
      related to the amount of c-AMP. This amount of c-AMP in connection with
      neurotransmitters controls the axoplasmic transport, which in turn is related to
      the activity of the neuron.

PMID- 7505857
TI  - Optical probing of active membrane potential using lasers and microoptics.
AB  - We developed an optical probing system of active membrane potentials using lasers
      and microoptics. We measured the action potential of carp heart by multiple
      wavelength and multiple-site optical probing system. Taking advantage of the
      coherent laser beam, an optical microprobing method for micro-study on ion
      channel activity is proposed.

PMID- 7505858
TI  - The origin of rapid changes in birefringence, light scattering and dye absorbance
      associated with excitation of nerve fibers.
AB  - By comparing the time-courses of rapid optical changes in the garfish olfactory
      nerve evoked by electric stimulation with those of mechanical changes observed at
      the site of optical recording, the origin of optical changes in the nerve has
      been investigated. Based on the finding that the time-course of the birefringence
      change accurately coincides with that of swelling of the nerve, optical changes
      are interpreted as being brought about by invasion of water into the superficial
      layer of the nerve fibers. A close relationship has also been demonstrated
      between nerve swelling and changes in light scattering and in dye absorbance.

PMID- 7505859
TI  - Effect of morphine on changes in cutaneous blood flow induced by antidromic
      stimulation of primary afferent fibers in the hind instep of rats.
AB  - The effects of morphine on the release of immunoreactive substance P (iSP) into
      the subcutaneous perfusate and the changes in cutaneous blood flow (CBF) elicited
      by antidromic stimulation of sectioned sciatic nerve were investigated in the
      instep of the hind paw of rats. Antidromic stimulation of the sectioned sciatic
      nerve induced a marked increase in iSP release into the subcutaneous perfusate
      and a biphasic flow response consisting of an initial transient decrease followed
      by an increase. Both the iSP release and the increase of the CBF evoked by
      antidromic stimulation (the second phase) were significantly inhibited by intra
      arterial (i.a.) infusion of morphine (30 mumol/kg). These inhibitory effects of
      morphine were antagonized by pretreatment with naloxone (2 mg/kg, i.p.). The i.a.
      infusion of SP (0.25 mumol/kg) induced a biphasic flow response similar to that
      elicited by antidromic stimulation of the sectioned sciatic nerve. Neither phase
      induced by i.a. infusion of SP was affected by preinfusion of morphine (10 or 30
      mumol/kg, i.a.). We suggest that morphine applied locally mainly acts on the
      peripheral endings of small-diameter afferent fibers, not on blood vessels, and
      that activation of this site is involved in the regulation of the
      microcirculatory hemodynamics of cutaneous tissue through inhibition of SP
      release.

PMID- 7505860
TI  - Effects of quinotolast, a new orally active antiallergic drug, on experimental
      allergic models.
AB  - The effects of a new antiallergic drug, quinotolast [sodium 5-(4-oxo-1-phenoxy-4H
      quinolizine-3-carboxamido)tetrazolate monohydrate], were studied and compared
      with those of tranilast, amlexanox, pemirolast, repirinast and disodium
      cromoglycate (DSCG) in experimental allergic models. Quinotolast potently
      inhibited such type I allergic reactions as passive cutaneous anaphylaxis (PCA)
      and anaphylactic bronchoconstriction in rats by both intravenous and oral dosing.
      All of these effects were stronger than those of the reference drugs tested.
      Quinotolast inhibited histamine release from rat peritoneal cells, but it had no
      antagonistic effect on histamine-, serotonin-, platelet activating factor- or
      bradykinin-induced cutaneous reactions in rats. Moreover, it was clearly
      demonstrated that quinotolast and DSCG had a cross tachyphylaxis to inhibit PCA
      in rats, suggesting that these drugs, at least in part, share the same mechanism
      of action. Furthermore, quinotolast potently inhibited PCA in guinea pigs in
      which DSCG and other reference drugs showed poor inhibitory activity. Quinotolast
      also showed stronger inhibitory effects on histamine and peptide leukotrienes
      release from guinea pig lung fragments or mouse cultured mast cells than the
      other drugs tested. Thus, the effect of quinotolast on type I allergic reaction
      would seem to be based on an inhibition of mediator release from inflammatory
      cells including mast cells. The results suggest that quinotolast will be
      beneficial in the treatment of type I allergy-related diseases.

PMID- 7505861
TI  - New developments in the search for improved antiepileptic drugs.
AB  - Recent advances in neurobiology have yielded clues about the abnormal physiology
      of epilepsy and a better understanding of the action of the established
      anticonvulsants, which were discovered fortuitously or in animal screening tests.
      Some newer antiepileptic drugs may represent an important improvement over
      existing therapy, especially if they show efficacy in patients with intractable
      seizures or fewer limiting neurological side effects. Many developmental agents
      are designed to interact with a specific target and employ one of three
      strategies: enhancement of central inhibition; diminution of central excitation;
      or modulation of ionic channels regulating neuronal excitability. This article
      reviews the anticonvulsant compounds in development, with a focus on those being
      investigated in man. Updated information is also provided about the mechanisms of
      action of the antiepileptic drugs presently used as first line therapy.

PMID- 7505862
TI  - Anterior extensive corpus callosotomy including resection of the isthmus.

PMID- 7505864
TI  - A system for measuring electrophysiological multiple unit activity and
      extracellular dopamine concentration at single electrodes.
AB  - A technique is described for measuring electrophysiological multiple-unit
      activity and extracellular dopamine concentration with in vivo voltammetry at an
      array of 8 electrodes. In addition, new procedures in the construction of the
      voltammetric electrode that reduce the effects of capacitance and improve
      sensitivity are outlined. A system of relays controlling the connections of the
      electrode and associated systems is also detailed. Both in vitro and in vivo
      voltammetric selectivity tests indicate an almost exclusive response to dopamine.
      A large increase in extracellular dopamine concentration was detected in response
      to 2.5 mg/kg D-amphetamine. Both prestimulus and cortical stimulation evoked
      increases in striatal multiple-unit activity were measured.

PMID- 7505863
TI  - Diurnal rhythm of 5HIAA release determined by in vivo microdialysis in freely
      moving rats.

PMID- 7505866
TI  - Janus Green B as a rapid, vital stain for peripheral nerves and chordotonal
      organs in insects.
AB  - Effective staining of peripheral nerves in live insects is achieved with the
      vital stain Janus Green B. A working solution of 0.02% Janus Green B in saline is
      briefly applied to the exposed peripheral nervous system. The stain is then
      decanted and the dissection flooded with fresh saline, resulting in whole nerves
      being stained dark blue in contrast to surrounding tissues. This simple and
      reliable technique is useful in describing the distribution of nerves to their
      peripheral innervation sites, and in locating small nerve branches for
      extracellular physiological recordings. The stain is also shown to be useful as a
      means of enhancing the contrast between scolopale caps and surrounding tissues in
      chordotonal organs, staining chordotonal organ attachment strands, and the crista
      acustica (tympanal organ) of crickets and katydids. The advantages of Janus Green
      B over traditional peripheral nerve strains, in addition to its shortcomings, are
      discussed.

PMID- 7505865
TI  - Different sets of afferents are demonstrated by the fluorescent tracers fast blue
      and rhodamine.
AB  - The fluorescent retrograde tracers Rhodamine B Isothiocyanate (RITC) and Fast
      Blue (FB) were injected either into the thalamic nucleus rotundus or into the
      complexus neck muscle in pigeons. Both in the rotundal and the peripheral motor
      preparations RITC yielded a 3-5 times larger number of afferent ipsilateral
      neurones than FB. While RITC additionally labelled a large number of
      contralateral afferents, virtually no labelled cells were detected contralateral
      to the injection site using FB. This selective omission of the contralateral
      input with FB was identical for both neural systems despite differences in
      injection volume, survival time, and transport length. In the present case, this
      structure-specific sensitivity of FB would lead to the erroneous conclusion that
      contralateral afferents are virtually non-existent in the visual tectofugal and
      the peripheral motor system. Thus, these results make it likely that the choice
      for a certain tracer may lead to different connectional interpretations of a
      neural system. Although the mechanism for these structure-specific sensitivity
      differences are unknown, it is suggested that tracers with lower effectivity like
      FB may be unable to label afferent structures with fewer axon terminals.

PMID- 7505867
TI  - A method for utilizing biocytin to study retinofugal pathways at the light and
      electron microscopic levels.
AB  - Numerous methods have been utilized in the past to study the retinofugal pathway
      at both the light and electron microscopic levels. However, many of these
      techniques have technical drawbacks that make them difficult to use in electron
      microscopic studies. We present herein a method for utilizing the anterograde
      tracer biocytin to study the retinal pathways at both the light and electron
      microscopic levels. Biocytin is an especially useful tracer since it clearly
      labels very small axons and boutons in addition to the larger fibers. In
      addition, the synaptic ultrastructure is left intact and the technique can be
      utilized in numerous double-labeling neuroanatomical studies.

PMID- 7505868
TI  - An improved staining technique for cytochrome C oxidase.
AB  - Cytochrome C oxidase (CO) has been shown to be an indicator of neuronal activity
      in the brain. In the primate visual cortex, CO staining also differentiates cell
      populations encoding visual properties such as color, contrast, ocularity, and
      movement. We have developed a modified method which dramatically enhances the
      intensity and contrast of CO staining. This method can be applied to both fixed
      and non-fixed tissues. The sensitivity of this method is sufficiently high that,
      even after years of storage, tissues can still be well stained for CO activity.
      Such tissue is poorly stained with current methods. This CO staining technique
      may also be useful for double labeling of CO with other anatomical markers.

PMID- 7505869
TI  - Prostate-specific antigen: critical issues for the practicing physician.
AB  - BACKGROUND: Serum prostate-specific antigen (PSA), when used in combination with
      existing detection methods, improves the clinician's ability to detect early and
      potentially curable prostate cancer. FINDINGS: This report describes clinically
      important issues about use of the serum PSA concentration for detecting early
      prostate cancer. Other PSA-related factors--PSA density, PSA velocity, and age
      specific reference ranges--seem to enhance the ability of clinicians to
      distinguish benign prostatic conditions from early prostate cancer. Because
      digital rectal examination only minimally affects the serum PSA concentration,
      delaying a determination after this examination is unnecessary. Finasteride
      therapy for benign prostatic hyperplasia should be initiated only after the
      prostate has been evaluated for cancer because this 5 alpha-reductase inhibitor
      lowers the serum PSA value by approximately 50%; however, reassessment of the
      prostate for cancer is necessary if the PSA level fails to decrease as expected
      or increases to more than 2 ng/mL during finasteride treatment. CONCLUSION:
      Currently, PSA is the most important, accurate, and clinically useful tumor
      marker for prostate cancer.

PMID- 7505870
TI  - Prostate-specific antigen: concepts for staging prostate cancer and monitoring
      response to therapy.
AB  - FINDINGS: The prostate-specific antigen (PSA) level alone does not facilitate
      precise pathologic staging on an individual basis, although advanced stage tends
      to correlate with an increased PSA level. The staging accuracy of PSA, however,
      can be enhanced by considering the variables of tumor grade and clinical stage.
      Staging radionuclide bone scans in asymptomatic, untreated patients with
      clinically localized prostate cancer and a PSA value of less than 10.0 ng/mL are
      unnecessary. After radical prostatectomy, the serum PSA level is exquisitely
      sensitive to recurrent or residual disease. Ultrasensitive PSA assays can
      increase the sensitivity of PSA as a tumor marker after surgical removal of the
      prostate. Currently, however, the clinical usefulness of PSA concentrations
      detected in the ultrasensitive range after radical prostatectomy is unknown.
      Serum PSA values aid in monitoring patients who have received definitive
      radiation therapy for prostate cancer. Patients in whom the serum PSA level
      decreases to the reference range have a favorable prognosis. An increasing serum
      PSA concentration after radiation therapy heralds progressive prostate cancer.
      The serum PSA level after androgen deprivation therapy (ADT) also has prognostic
      importance in that a decrease to the normal range predicts a prolonged remission
      in most patients. Because expression of PSA is under direct hormonal influence,
      however, ADT can decrease the serum PSA value independent of antitumorigenic
      activity. Patients who have received ADT must be closely monitored for signs of
      clinical progression because, in some patients, a serum PSA concentration within
      the reference range may underestimate actual tumor burden and activity.
      CONCLUSION: PSA is the most useful and accurate tumor marker for staging and
      monitoring prostate cancer after therapy.

PMID- 7505871
TI  - [FK506: an immunosuppressor for the '90's?].

PMID- 7505872
TI  - High-strength pancreatic enzyme supplements and large-bowel stricture in cystic
      fibrosis.

PMID- 7505874
TI  - alpha-Macroglobulins: detection and characterization.

PMID- 7505873
TI  - A new variant of serosubtype P1.16 in Neisseria meningitidis from Norway,
      associated with increased resistance to bactericidal antibodies induced by a
      serogroup B outer membrane protein vaccine.
AB  - Based on differences in reaction pattern with monoclonal antibodies against the
      P1.16 epitope, a new variant of the class 1 protein in Neisseria meningitidis
      serogroup B was identified in Norway. A single amino acid deletion was revealed
      when the part of the gene region encoding the second variable region of the
      protein was sequenced. This new variant was designated P1.16c. About 5% of the
      B:15:P1.7,16 strains in Norway from the time period 1987-1991 were P1.16c. In a
      localized area in Southern Norway, 5/8 (62%) of the P1.7,16 strains were P1.16c.
      The P1.16b mutant, recently described in England, was not found among the
      Norwegian meningococcal isolates. Strains carrying the P1.16c mutation showed
      increased resistance to bactericidal killing, not only by P1.16-specific
      monoclonal antibodies, but also by the sera from individuals immunized with a
      vaccine based on outer membranes from a B:15:P1.7,16 strain.

PMID- 7505875
TI  - Immunogenicity of Vibrio cholerae O1 fimbriae in animal and human cholera.
AB  - Parenteral immunization with either formalin-fixed whole cells of the fimbriate
      Bgd17 strain or purified fimbriae protected against Vibrio cholerae O1 infection
      in rabbits, independent of biotype and serotype. Parenteral immunization of adult
      rabbits with purified fimbriae prior to V. cholerae O1 challenge resulted in a
      reduction of 2 to 3 orders of magnitude in the number of bacteria recovered from
      the small intestines of immunized rabbits in comparison to non-immunized
      controls. IgG and IgA antibodies against fimbrillin of V. cholerae O1 were
      detected in the convalescent sera of patients with cholera; however, little
      fimbrial antigen was detected in the commercially available cholera vaccines when
      examined by polyclonal and monoclonal antibodies against fimbriae. These data
      suggest that fimbrial hemagglutinin is a major adhesin of V. cholerae O1 and that
      parenteral immunization with fimbriae generates a specific immune response in the
      gut that may serve as one means of mitigating subsequent V. cholerae O1 gut
      infection.

PMID- 7505877
TI  - Randomized study for the treatment of adult advanced Hodgkin's disease:
      epirubicin, vinblastine, bleomycin, and dacarbazine (EVBD) versus mitoxantrone,
      vinblastine, bleomycin, and dacarbazine (MVBD).
AB  - Seventy patients with previously untreated advanced Hodgkin's disease and without
      bulky disease were entered in a prospective randomized clinical trial comparing
      epirubicin in combination with vinblastine, bleomycin, and dacarbazine (EVBD)
      with a regimen containing mitoxantrone, vinblastine, bleomycin, and dacarbazine
      (MVBD). Both groups were comparable for the variables of age, sex, stage, and
      presence of B symptoms and histology. Thirty-one (88%) of EVBD-treated patients
      achieved a pathologically documented complete remission (CR) compared to the 24
      cases (68%) of the MVBD-treated group. After a median follow-up of 36 months,
      duration of CR is better in the EVBD-treated patients with an actuarial 5-year
      duration of CR of 80%, statistically different to the MVBD group: 53% (P < 0.01).
      Both regimens showed the same gastrointestinal toxicity, but the patients treated
      with the MVBD regimen shown most and severe hematological and cardiac toxicities.
      Also, biochemical alterations in hepatic test were observed in these patients.
      The alternative use of epirubicin in combination chemotherapy appears to be as
      effective in advanced Hodgkin's disease without bulky disease, with reduced
      clinical toxicity. Mitoxantrone containing regimen was not found to have an
      equivalent efficacy and clinical toxicity was most frequent and severe. We felt
      that mitoxantrone could be consider a second-line drug in the treatment of
      advanced Hodgkin's disease.

PMID- 7505876
TI  - Evaluation of six tumor markers in patients with carcinoma of unknown primary.
AB  - We have retrospectively evaluated six serum tumor markers in 85 patients with
      carcinoma of unknown primary. The serum levels of carcinoembryonic antigen (CEA),
      CA 19-9, CA 15-3, CA 125, beta-chorionic gonadotropin (beta-HCG) and alpha
      fetoprotein (AFP) were related with the histological pattern (undifferentiated
      carcinoma or adenocarcinoma), the number and the site of metastases, as well as
      the response to chemotherapy and the patients' survival. More than 40% of the
      patients had increased serum levels of all six tumor markers, except of AFP which
      was found to be increased in only 17% of them. Increased levels of CA 19-9 were
      related to metastatic adenocarcinoma, whereas CA 19-9 and CA 15-3 had a
      relationship with more advanced disease. Patients with liver involvement had
      higher mean levels of CEA and CA 19-9 as compared to those with nodal disease.
      None of these markers was found to have a predictive value for response to
      chemotherapy or survival. Although the present study has a retrospective nature,
      it allows us to conclude that patients with CUP have a nonspecific over
      expression of the above serum tumor markers and that routine use of these markers
      does not offer any diagnostic or prognostic assistance.

PMID- 7505878
TI  - [Hepatic protein synthesis in regenerating liver after partial hepatectomy].
AB  - The process of hepatic protein synthesis was studied in the regenerating liver
      after partial hepatectomy (HTX). Hepatocellular protein synthesis (HPS) and
      secretory protein synthesis (SPS) were determined in the regenerating liver of
      rats after 68% HTX. The serum levels of the following items were determined in 10
      patients before and after HTX: interleukin-6 (IL-6), acute-phase proteins (APP),
      and negative acute-phase proteins (NAPP). HPS has markedly increased after HTX,
      with the peak occurring at 48 hours. The regenerating rat liver showed an
      increase of 80% over normal livers in HPS and 200% in SPS 48 hours after HTX. A
      remarkable increase in IL-6 levels occurred on the first day after HTX. In all
      patients transient falls in APP levels occurred on the first day. Values appeared
      to return rapidly toward preoperative values by 3 or 5 days after HTX but failed
      to show any significant increase compared to preoperative values. In contrast to
      APP, prolonged decreases in NAPP levels occurred after HTX. Values declined to a
      nadir on the first or third day after HTX and remained suppressed for 14 days.
      These results suggest that the production of APP is activated at an early stage
      of liver regeneration after partial hepatectomy.

PMID- 7505879
TI  - [The analysis of homing receptors on peripheral blood lymphocytes in cancer
      patients: preliminary report].

PMID- 7505880
TI  - Identification of the binding site of two monoclonal antibodies to human
      protamine.
AB  - We have previously developed a number of monoclonal antibodies (Mabs) that bind
      to protamine. One of these antibodies, Hup1N, binds to human protamine 1 but not
      to protamine 2. In contrast, Mab HupA binds both protamine 1 and protamine 2. The
      epitopes for these two Mabs were observed to overlap, and were localized to the
      evolutionarily conservative amino-terminal region of protamine 1. This assignment
      is based on antibody binding to protamine from different species in which the
      protamine sequence is known, as well as analysis of antibody binding to synthetic
      peptides and synthetic peptides with specific amino acid substitutions.

PMID- 7505881
TI  - Epitope mapping of the site(s) of binding of Fc epsilon RII/CD23 within human
      IgE. Determination of the B lymphocyte-binding sites by use of synthetic peptides
      and anti-peptide antibodies representative of linear Fc sequences.
AB  - The work undertaken has investigated the structure-function relationship between
      IgE and its low affinity receptor on B lymphocytes. To identify sites on the IgE
      molecule which interact with the low affinity receptor (Fc epsilon RII/CD23), 10
      different peptide sequences within the CH2, CH3 and CH4 domains of human IgE were
      selected according to charge, overall hydrophobicity and possible accessibility
      on native IgE sequences. Peptides representative of these were synthesized by the
      solid phase procedure; and their cytophilic activities were examined by
      determining their capacity to inhibit the binding of radiolabelled or erythrocyte
      bound IgE to a Fc epsilon RII/CD23 positive B cell line (RPMI-8866). Moreover,
      these linear sequences were rendered immunogenic by conjugation to a protein
      carrier (KLH) and used to produced polyclonal antibodies in rabbits. The
      reactivity of the anti-peptide antibodies with both free peptides and native IgE
      bound to a solid phase, as well as their capacity to inhibit binding of IgE to a
      Fc epsilon RII/CD23 positive cell line, were investigated. Results from such use
      of peptides and anti-peptide antibodies indicate that two sequences,
      representative of residues 364-383 and 401-415, could be involved in the binding
      of IgE to both membrane-bound and soluble form Fc epsilon RII/CD23; indicating
      that the B lymphocyte-binding site on human IgE may be restricted to the CH3
      domain.

PMID- 7505882
TI  - A single amino acid substitution in the H-2Kb molecule generates a defined
      allogeneic epitope.
AB  - Using Mitomycin C mutagenesis and negative and positive selection with monoclonal
      antibodies specific for H-2Kb and H-2Kbm10, respectively, a mutant cell line
      clone, Mitc-182, was isolated. Direct sequencing of uncloned cDNA as well as PCR
      based cloning and sequencing of the H-2Kb182 transcript from this mutant revealed
      a single G-->T transversion resulting in the substitution of Trp167 by cysteine.
      Serologically, the mutant Kb182 and Kbm10 are almost identical as each has lost
      at least five Kb specific mAb epitopes and gained several new epitopes.
      Interestingly, the mutant cell line, Mitc-182, is efficiently recognized by
      alloreactive CTLs raised in reciprocal combinations, e.g. CB6 anti Cbm10 and
      Cbm10 anti CB6, indicating that Kb182 contains both Kb and Kbm10 specific
      epitopes. The mutation has not affected the ability of Kb182 to present Kb
      restricted antigenic peptides of Sendai and vesicular stomatitis viruses. In
      addition to underscoring the importance of amino acid residue 167 in
      alloreactivity, these results indicate a positive correlation between the gain of
      both an mAb epitope and a defined alloreactive CTL epitope.

PMID- 7505883
TI  - Characterization of the invariant chain C-terminus (Glu183-Glu193) epitope which
      is obscured in processed Ii, MHC alpha,beta trimers.
AB  - The E1 serum was developed against invariant chain peptide Ii (183-193) in order
      to study the function of the Ii protein which associates with class II MHC
      alpha,beta chains from time of synthesis until cleavage and release, possibly
      regulating the binding of antigenic peptides. Subpopulations of Ii, Ii(VIC) and
      Ii(E1), respectively, were demonstrated by sequential immunodepletions and
      immunoprecipitations with: (1) VIC-Y1 monoclonal antibody to an N-terminal
      epitope of Ii, and (2) E1 rabbit antiserum to Ii(183-193). In 3 hr radiolabeled
      cells, VIC-Y1 recognized Ii, Ii and N- and O-linked glycosylation (IpN, IpO), p41
      and co-precipitated class II alpha,beta chains, while E1 recognized Ii, IpN and
      immature Ii-alpha complex. In 15 min radiolabeled cells, each antibody recognized
      similar, immature Ii forms without alpha,beta. Urea denaturation of Ii(VIC)
      rendered the main Ii species but not IpO immunoprecipitable with E1. E1
      recognized O-glycanase-treated Ii (VIC). We conclude that the Ii(183-193) epitope
      was obscured by interactions of Ii with class II alpha,beta chains and by the O
      linked glycosylation of Thr187, which may in part regulate association of Ii to
      class II alpha and beta chains.

PMID- 7505884
TI  - Specific disengagement of cell-bound anti-LAM-1 (anti-L-selectin) antibodies by
      aurintricarboxylic acid.
AB  - Brief treatment of human peripheral blood lymphocytes with the potential anti-HIV
      compound aurintricarboxylic acid (ATA) prompts the selective release of already
      bound L-selectin-specific anti-Leu8 and anti-LAM1-1 antibodies from the cells.
      Two other anti-LAM1 antibodies, anti-LAM1-3 and anti-LAM1-5 stay antigen-bound at
      the same time. Interestingly, the ATA-sensitive anti-Leu8 strongly competes with
      the ATA-resistant anti-LAM1-3 for binding. Photobleaching fluorescence resonance
      energy transfer (pFRET) measurements on flow-sorted cells suggests that these two
      antibodies compete for the same epitope, while anti-LAM1-5-FITC and anti-Leu8-PE
      bind to distinct sites, although they also compete for binding. Combining the
      data on competition, pFRET and ATA effect, we suggest that the ATA sensitive anti
      Leu8 and resistant anti-LAM1-3 bind to overlapping but non-identical epitopes.
      This remarkably specific effect may be exploited for designing anti-inflammatory
      drugs that modulate leukocyte adhesion.

PMID- 7505885
TI  - Screening for prostate cancer. Does it make a difference?
AB  - Susan's father, Sidney Smith, is 63 years old. Recently he has heard on radio and
      television talk shows that a new test, the Prostate Specific Antigen (PSA), is
      now available to check for prostate cancer. During his general check-up visit to
      your office, he mentions this test and wants to know more. He is in excellent
      health and his urinary review of systems reveals only a slight decrease in the
      intensity of his urinary stream. On examination he has moderate prostate
      enlargement but no palpable nodules. His stool test is Hemoccult negative. The
      remainder of his examination is normal.

PMID- 7505886
TI  - Chemotherapy of testicular cancer: 10-year experience.
AB  - A total of 250 patients with germ cell testicular tumors were treated by PVB
      chemotherapy between 1982 and 1992. Mean age of patients was 28.9 years (range 15
      52). Thirty-four patients in clinical Stage II (11 patients IIA, 13 patients IIB,
      and 10 patients IIC) underwent primary retroperitoneal lymphadenectomy (RPL) with
      subsequent chemotherapy. They were followed-up for a mean of 106.3 months (range
      85-125). CR was achieved in 30 patients (88.2%). Three patients relapsed. Twenty
      seven patients (79.4%) are alive with no evidence of disease (NED) after a
      minimum of 5 years since the start of therapy. One hundred and twenty-two
      patients underwent primary chemotherapy for clinical Stages IM (15 patients), IIA
      (31 patients, IIB (48 patients) and IIC (28 patients) with RPL in cases with
      residual mass in the retroperitoneum. They were followed-up for a mean of 47.7
      months (range 6-122). CR was achieved in 115 patients (92.7%) (75 of them
      received chemotherapy alone, 40 patients achieved CR following combined
      cytostatic-surgical treatment). Eleven patients relapsed. One hundred and nine
      patients (89.3%) are alive with NED. Ninety-four patients in Stages III and IV (8
      patients III, 86 patients IV) underwent primary chemotherapy with additional
      surgical removal of residual metastases. They were followed-up for a mean of 50.5
      months (range 6-125). CR was achieved in 65 patients (69.1%) (32 of them received
      chemotherapy alone, 33 patients achieved CR following combined cytostatic
      surgical treatment). Eleven patients relapsed. Fifty-seven patients (60.6%) are
      alive NED. There were 11 patients with advanced germ cell testicular cancer
      (Stages IIC and IV) who underwent initial PVB chemotherapy without previous
      orchiectomy. Delayed orchiectomy was done simultaneously with surgical removal of
      residual mass in the retroperitoneum or in the lungs or at completion of
      chemotherapy alone. The toxicity of chemotherapy was moderate. There were drug
      related deaths in ten patients (4%).

PMID- 7505887
TI  - Polarographic reduction and carcinogenic index tg alpha of 5-aza nucleosides
      possessing antileukemic activity.
AB  - Polarographic behavior of arabinosyl-5-azacytosine (ara-AC) and 5-azacytidine in
      anhydrous dimethylformamide and in Britton Robinson buffer is described. 5
      Azacytidine and ara-AC underwent two-electron reduction under the polarographic
      conditions used. Carcinogenic index tg alpha estimated in the presence of alpha
      lipoic acid was 0.295 for 5-azacytidine and 0.275 for ara-AC.

PMID- 7505888
TI  - Relation of some cytochemical activities to the expression of CD34 marker in
      acute leukemia.
AB  - The blast cells of peripheral blood and bone marrow of eleven acute leukemia
      patients with CD34 surface membrane antigen expression were investigated by
      immunophenotyping, cytochemistry and biochemical analysis. CD34 expression is a
      characteristic marker of very immature leukemic cells. Nine of eleven CD34+ acute
      leukemia cases had the immunophenotype of poorly differentiated myeloid cells.
      CD34+ blasts of two patients expressed the phenotype of very early lymphoid
      differentiation. Significant correlation was found between the expression of HLA
      DR and CD34. The absence of CD10 antigen expression was observed in all cases of
      CD34+ myeloid blasts. The strong activity of SBB along with simultaneous absence
      of light microscopy MPO staining, 5'NT and moderate BG reactivity were
      characteristic enzyme features of CD34+ myeloid cells. The enzyme features of
      more mature stages of myeloid differentiation lacked. In lymphocytes, the CD34
      expression correlated with CD10 antigen positivity and 5'NT activity. The
      activity of ADA was higher than that of PNP in all cases of CD34+ acute leukemia
      blast cells. The SBB, 5'NT and BG reactivity in correlation to CD34 antigen
      expression in acute leukemia may be an additional marker of very early stages of
      differentiation, either lymphoid or myeloid. The contribution to clinically
      important differential diagnosis of immature acute leukemia is discussed.

PMID- 7505889
TI  - Effects of long-term recovery from transient cerebral ischemia in rat brain:
      tissue levels of acetylcholine, monoamines, and their metabolites.
AB  - Concentrations of acetylcholine and the monoaminergic neurotransmitters dopamine,
      serotonin and their respective metabolites 3,4-dihydroxyphenylacetic acid
      (DOPAC), 4-hydroxy-3-methoxy-phenylacetic acid (HVA), 5-hydroxyindolacetic acid
      (5-HIAA) and choline were simultaneously determined in the corpus striatum of
      rats after 15 min. complete cerebral ischemia (CCI) and in different intervals
      (1, 24, 48, 72, 96 hours) of postischemic cerebral reperfusion. Results were
      compared to respective sham-operated control animals. After 15 min. CCI
      acetylcholine concentration decreased to 15%, and dopamine concentration to 56%
      of the control values. The metabolite levels of DOPAC decreased to 40% and HVA to
      64% of the control values. Acetylcholine, dopamine, serotonin and choline
      concentrations were not changed significantly after reperfusion. The metabolites
      HVA and 5-HIAA showed their maximum increases after 1 and 24 hours of
      reperfusion, additionally HVA was decreased both, after 72 and 96 hours of
      reperfusion. The data indicate that surprisingly little permanent damage could be
      caused by a 15 min. ischemia in the striatum. Tissue levels of the
      neurotransmitters appeared differentially altered but similarly regulated during
      ischemia and subsequent recirculation. Acetylcholine and dopamine levels
      decreased profoundly during ischemia. However, acetylcholine levels could be
      compensated rapidly during reperfusion, whereas the dopaminergic system showed a
      long-lasting change in its turnover rate. Although serotonin levels were
      unaffected by CCI, there was an increase of its presumed turnover rate during
      reperfusion.

PMID- 7505890
TI  - Effects of chronic brofaromine administration on biogenic amines including
      sulphatoxymelatonin and acid metabolites in patients with bulimia nervosa.
AB  - Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A)
      was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R
      criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled
      overeating episodes are accompanied by purging activities and extreme concerns
      about body shape and weight. The following indices were measured: plasma and
      urinary phenylacetic acid (PAA), homovanillic acid (HVA), vanillylmandellic acid
      (VMA); plasma tryptamine (T), beta phenylethylamine (PE), and 5
      hydroxyindoleacetic acid (5-HIAA) and urinary 6-sulphatoxymelatonin (aMT6s). PE
      levels remained the same but T showed a trend toward elevation over time. Twenty
      four hour levels of urinary aMT6s in BN patients were higher at week 4 when
      compared to baseline and week 8. There was a significant reduction in plasma VMA
      and HVA over time during treatment with brofaromine and both plasma HVA and VMA
      were significantly lower for the brofaromine group compared to placebo at week 4.
      Plasma 5-HIAA was significantly higher for the brofaromine group after 8 weeks
      when compared to placebo. Urinary VMA decreased significantly from baseline to
      week 4 with a partial elevation at 8 weeks. Urinary VMA was also significantly
      lower in patients on brofaromine at week 4. This study verifies that brofaromine
      complies with predicted MAO-A inhibiting patterns in a clinical population.

PMID- 7505891
TI  - Higher environmental temperature-induced increase in body temperature:
      involvement of serotonin in GABA mediated interaction of opioidergic system.
AB  - Exposure (2 h) of adult male albino rats to higher environmental temperature
      (HET, 40 degrees C) significantly increased body temperature (BT). Administration
      of (a) 5-HTP (5 mg/kg, i.p.) or morphine (1 mg/kg, i.p.) or physostigmine (0.2
      mg/kg, i.p.) alone significantly increased and (b) methysergide (1 mg/kg, i.p.)
      or naloxone (1 mg/kg, i.p.) or atropine (5 mg/kg, i.p.) reduced the BT of both
      normal and HET exposed rats. Further, it was observed that morphine prevented the
      methysergide-induced hypothermia and 5-HTP potentiated the morphine-induced
      hyperthermia in both normal and HET exposed conditions. Biochemical study also
      indicates that serotonin metabolism was increased but GABA utilization was
      reduced following exposure to HET.5-HTP or bicuculline-induced hyperthermia in
      control and HET exposed rat was potentiated with the coadministration of
      bicuculline and 5-HTP. The cotreatment of bicuculline with methysergide prevented
      the methysergide-induced attenuation of BT of heat exposed rat, rather BT was
      significantly enhanced indicating that inhibition of GABA system under heat
      exposed condition may activate the serotonergic activity. Further (a) enhancement
      of (i) morphine-induced hyperthermia with physostigmine (ii) physostigmine- or
      morphine+physostigmine-induced increase of BT with 5-HTP and (b) reduction of (i)
      morphine- or morphine + 5-HTP-induced hyperthermia with atropine and (ii)
      atropine-induced hypothermia with 5-HTP in both normal and HET exposed conditions
      suggest that HET exposure activates the cholinergic system through the activation
      of opioidergic and serotonergic system and hence increased the BT. Thus, it may
      be concluded that there is an involvement of serotonergic regulation in the
      opioidergic-cholinergic interaction via GABA system in HET-induced increase in
      BT.

PMID- 7505892
TI  - Effects of ethanol on brain monoamine content of spontaneously hypertensive rats
      (SHR).
AB  - Spontaneously hypertensive rats (SHR) were administered either 2.4 g/kg ethanol
      or an isocaloric glucose daily for 4 weeks and the levels of norepinephrine (NE),
      epinephrine (EP), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid
      (5-HIAA) in different brain regions were determined. Results indicated a 3-fold
      increase in NE level in brain stem and hypothalamus and more than 2-fold increase
      in DA in corpus striatum in alcohol-treated rats as compared to controls. There
      was a significant increase in the level of DA in the corpus striatum but the
      levels in cerebral cortex, brain stem and hippocampus were decreased instead.
      Decreases in 5-HT levels were found in hypothalamus, brain stem, cortex and
      cerebellum of alcohol-treated brain as compared to untreated controls. These
      results indicate alterations of the biogenic amine contents in different regions
      of the SHR brain after chronic ethanol ingestion. Since stimulated release of
      biogenic amines in the SHR brain has been implicated in the regulation of blood
      pressure, changes due to ethanol ingestion may be a risk factor in hypertensive
      patients.

PMID- 7505894
TI  - Characteristics of histamine receptors in human cerebral arteries.
AB  - Histamine and 2,2-pyridylethylamine, an H1-receptor agonist, (both 10(-8)-10(-3)
      M) caused contraction of human cerebral artery preparations in the absence of
      active tension, while dimaprit, an H2-receptor agonist, caused vasorelaxation.
      The histamine-induced vasoconstriction was blocked non-competitively by
      tripelennamine, an H1-receptor antagonist. In the presence of cimetidine, an H2
      receptor antagonist, histamine-induced contraction was enhanced. The histamine
      induced contraction was not affected by phentolamine or propranolol, but
      abolished by nifedipine. In prostaglandin F2 alpha-precontracted arteries,
      histamine and dimaprit caused relaxation, while 2,2-pyridylethylamine had no
      apparent effect. Histamine-induced relaxation was much greater in the presence
      than in the absence of an H1-antagonist. The vasorelaxation induced by histamine
      in the presence of an H1-antagonist was also inhibited by an H2-antagonist.
      Histamine caused no apparent relaxation in precontracted preparations without
      endothelium. The present results provide further evidence that histamine causes
      either vasocontraction or vasodilation in human cerebral arteries, and suggest
      that vasocontraction and vasorelaxation are due to the activation of H1- and H2
      receptors, respectively. The relaxation induced by histamine may also be related
      to the endothelium-derived relaxing factors released from endothelial cells.

PMID- 7505893
TI  - Effects of DSP-4 on monoamine and monoamine metabolite levels and on beta
      adrenoceptor binding kinetics in rat brain at different times after
      administration.
AB  - Effects of DSP-4 on noradrenaline (NA), 3-methoxy-4-hydroxyphenyl glycol (MHPG),
      serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) levels and on beta
      adrenoceptor binding kinetics (Bmax and KD) in rat hippocampus, cortex and
      hypothalamus were studied between 24 hours and 14 days after systemic
      administration. Beta adrenoceptor numbers in hippocampus and cortex, but not in
      hypothalamus, were significantly increased after DSP-4. No significant changes in
      KD values were observed in hypothalamus, but significant increases in this
      parameter were measured in hippocampus and cortex. NA and MHPG levels were
      significantly decreased in all three brain regions, but MHPG/NA ratios were
      increased in hippocampus, decreased in cortex and unchanged in hypothalamus. Very
      prominent increases in 5-HIAA levels were observed in all three brain regions,
      but only at one day after DSP-4. The greatest increases in 5-HIAA levels occurred
      in the hippocampus, but this effect of DSP-4 appeared to be slightly diminished
      by pre-treatment with fluoxetine. In cortex and hippocampus 5-HT levels were
      slightly, but significantly decreased after DSP-4.

PMID- 7505895
TI  - Roles of embryonic astrocytes and Schwann cells in regeneration of adult rat
      dorsal root axons: qualitative observations.
AB  - Transplants of fetal spinal cord support regeneration of severed dorsal root
      axons and allow synapse formation. To analyze the components of the transplants
      that provide this favorable environment, we studied whether or not 1) the
      embryonic spinal cord transplants contain Schwann cells, a major producer of
      laminin, and 2) whether dorsal roots regenerate into transplants of immature
      astrocytes. We used calcitonin gene-related peptide (CGRP), laminin and glial
      fibrillary acidic protein (GFAP) immunocytochemistry to identify regenerated
      axons, Schwann cells and astrocytes, respectively. CGRP-immunoreactive axons
      regenerated into embryonic day 14 fetal spinal cord transplants, but the
      transplant did not contain laminin. Dorsal roots immunoreactive for CGRP also
      regenerated into suspensions of cultured astrocytes. The transplanted astrocytes
      also favored the expression of laminin and GFAP. CGRP-labeled axons regenerated
      and distributed widely into the polycarbonate tubes coated with poly L-lysine and
      containing medium with or without cultured astrocytes. These results indicate
      that Schwann cells are not likely to account for dorsal root regeneration into
      transplants of fetal spinal cord and that astrocytes may in fact induce
      regeneration. Regeneration may also take place in response to various
      environments.

PMID- 7505896
TI  - Chronic subdural hematoma may be preceded by persistent traumatic subdural
      effusion.
AB  - The incidence of traumatic subdural effusion (TSE) was analyzed to clarify the
      relationship with subsequent chronic subdural hematoma (CSH) in 500 patients with
      head injury evaluated over a 36-month period. TSE occurred in 108 patients
      (21.6%), and CSH developed in 29 (5.8%) of these. The incidence of TSE was high,
      although only hospitalized patients were included because of the necessity for
      serial computed tomography. TSE frequently developed into CSH, and all CSH
      followed TSE. Therefore, TSE is closely associated with CSH and subdural effusion
      is probably a preliminary stage necessary for the formation of CSH.

PMID- 7505897
TI  - Epidermoid cysts of the callosal region--three case reports.
AB  - Three patients with rare epidermoid cyst in the callosal region are described,
      two adjacent and one in the corpus callosum. Computed tomography revealed
      atypical features, i.e. a large, well-defined high-density mass unenhanced
      postcontrast and a well-defined hypodense mass with marginal calcification in one
      case each. Such a diffuse high-density mass may be caused by hemorrhage, highly
      concentrated protein or calcification of keratinized debris within the cyst.
      Marginal calcification may occur for unknown reasons. The cysts were subtotally
      removed.

PMID- 7505898
TI  - Treatment of anterior sacral meningocele--case report.
AB  - A 30-year-old female presented with a long history of dysmenorrhea and severe
      constipation. Radiological evaluation and magnetic resonance imaging revealed
      findings characteristic of an anterior sacral meningocele. Surgical treatment
      through the posterior transsacral approach failed, because the neck and orifice
      of the meningocele were too large to perform a simple neck ligation. A second
      operation successfully resected the connecting dural stalk of the meningocele and
      reconstructed the thecal sac. Microsurgical reconstruction of the thecal sac
      through the transsacral approach is a favorable option even for a large
      meningocele with a wide neck and ostium.

PMID- 7505899
TI  - Penetrating injury of the transverse sinus by a nail-gun--case report.
AB  - A 46-year-old male presented with a penetrating injury of the transverse sinus
      caused by a nail-gun. Open craniotomy reflected a doughnut-shaped bone flap and
      the 45 mm long nail, which was fortunately only touching the edge of the sinus,
      successfully removed. A wide surgical exposure and careful manipulation of the
      embedded nail are important to avoid inadvertent injury to the venous sinus and
      the surrounding brain tissues during the surgical procedure.

PMID- 7505900
TI  - Intracranial cavernous angioma manifesting as subarachnoid hemorrhage--case
      report.
AB  - A 56-year-old male presented with a posterior fossa cavernous angioma manifesting
      as persistent headache with mild neck stiffness. Lumbar puncture revealed
      subarachnoid hemorrhage (SAH). Repeated four-vessel angiography failed to
      identify the source of the SAH. Magnetic resonance (MR) imaging demonstrated
      multiple small lesions in the posterior fossa and cerebral hemispheres, and the
      SAH. A mass arising from the biventral lobule of the right cerebellar hemisphere
      extended exophytically into the cisterna magna with intratumoral hemorrhage.
      These findings were compatible with the presumptive diagnosis of SAH from the
      mass at the right biventral lobule. The lesion was totally removed through a
      suboccipital craniectomy without sequelae. The histological diagnosis was
      cavernous angioma. Intracranial cavernous angioma presenting only as SAH has
      never been reported before. The use of MR imaging in establishing the diagnosis
      of vascular malformations is emphasized, particularly when neither computed
      tomography nor angiography can adequately visualize the origin of SAH.

PMID- 7505901
TI  - Unusual meningeal tuberculoma--case report.
AB  - A 60-year-old male presented with bilateral papilledema. Neuroimaging showed a
      densely enhanced flat tumor within the interhemispheric region in the frontal and
      parietal lobes with sulcal obliteration and enhancement. There was no history of
      tuberculous infection. Histological examination of the excised tissue from the
      flat tumor within the interhemispheric region was consistent with tuberculoma.
      Multiple antituberculous agent therapy resolved the papilledema and reduced the
      tumor.

PMID- 7505902
TI  - Management of a broken atrial catheter migrated into the heart: a rare
      complication of ventriculoatrial shunt--case report.
AB  - A 21-year-old male, who had undergone a ventriculoatrial shunt for hydrocephalus
      5 years previously, became stuporous. A roentgenogram revealed that the distal
      segment of the broken atrial catheter had migrated and become lodged in the
      heart. Because the fragment had not adhered to the myocardium, it was easily
      retrieved by the transvenous approach with a retriever catheter. If the migrated
      catheter does not adhere to the myocardium, transvenous catheter retrieval is
      absolutely necessary. If, however, the migrated catheter adheres to the
      myocardium, an open thoracotomy would be required for retrieval, or the
      alternative of warfarin administration without retrieval may be the treatment of
      choice, as long as other problems do not occur.

PMID- 7505903
TI  - Transbrachial approach with turn over technique for selective cerebral
      angiography--technical note.
AB  - A new technique to obtain selective internal carotid, external carotid and
      vertebral artery angiograms through the transbrachial route using a special 4-Fr
      long catheter and long guidewire positioned by a turn over technique is
      described. The technique was used in 25 geriatric patients to obtain angiograms
      without persistent complications.

PMID- 7505904
TI  - Three-dimensional Hi-vision system for microneurosurgical documentation based on
      wide-vision telepresence system using one camera and one monitor.
AB  - A three-dimensional (3-D) high-definition television (Hi-Vision) system suitable
      for attachment to a stereoscopic operating microscope allowing 3-D medical
      documentation using one Hi-Vision camera and one Hi-Vision monitor is described.
      The system provides 3-D high-definition microneurosurgical recorded images
      suitable for viewing on a screen or monitor, or for printing.

PMID- 7505905
TI  - Serum alpha 2-macroglobulin in haemodialysis patients: baseline and kinetic
      studies.
AB  - The pathogenesis of dialysis related amyloidosis remains unresolved despite the
      identification of beta 2-microglobulin (beta 2M) as the major protein
      constituent, as well as other proteins being present in the deposits. Among the
      latter we have assessed the serum concentrations of alpha 2-macroglobulin (alpha
      2M) both in the baseline stage and during the haemodialysis (HD) procedure. We
      have also assessed the influence of the membrane on alpha 2M kinetics. Fifteen HD
      patients with histologically proven dialysis-related amyloidosis (DRA group) and
      15 HD patients clinically and radiologically considered dialysis-related
      amyloidosis free (control group) were included in the baseline study. Blood was
      sampled the day before the second dialysis of the week and alpha 2M, beta 2M and
      alpha 1 antitrypsin were determined along with the routine biological analysis of
      these patients. Serum alpha 2M was greater in dialysis-related amyloidosis than
      in control patients (t = 2.35; P < 0.026). Serum beta 2M was similar in both
      groups. The serum alpha 2M and beta 2M correlated in patients with dialysis
      related amyloidosis (r = 0.64; P < 0.01), while no correlation was found in
      controls (r = 0.17; NS). Stepwise analysis taking the presence of dialysis
      related amyloidosis as the dependent variable retained the serum alpha 2M
      concentration as the first variable in the model (F = 4.4; partial r = 0.38; P <
      0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505906
TI  - Heparin-associated thrombocytopenia type II in a patient with end-stage renal
      disease: successful anticoagulation with the low-molecular-weight heparinoid Org
      10172 during haemodialysis.

PMID- 7505907
TI  - A neurofilament polypeptide and the glial fibrillary acidic protein share common
      epitopes in the variable region.
AB  - A polyclonal antibody against the high molecular weight neurofilament polypeptide
      (NF-H) obtained from cytoskeletal extracts of bovine spinal cord reacted with NF
      H, with the middle molecular weight neurofilament polypeptide (NF-M) and with a
      M(r) 51,000 polypeptide, but not with the low molecular weight neurofilament
      polypeptide (NF-L). The M(r) 51,000 polypeptide corresponded to the glial
      fibrillary acidic protein (GFAP), which forms the intermediate filaments of
      astrocytes. The polyclonal antibody affinity-purified with GFAP, reacted with
      both purified GFAP and NF-H. Digestion of NF-H with alpha-chymotrypsin was used
      to determine the recognition site of the affinity-purified antibodies. Only
      fragments of the tail domain of NF-H reacted with the antibody. We propose that
      common epitopes exist between the variable C-terminal domains of NF-H and GFAP.

PMID- 7505908
TI  - Nitric oxide synthase immunoreactive neurons in the rat kidney.
AB  - The presence of neurons with nitric oxide synthase (NOS) immunoreactivity was
      investigated in the rat kidney. Whole kidneys were examined by means of serial
      sections. The indirect immunocytochemical technique using polyclonal antibody
      raised against rat brain type Ia NOS and the histochemical technique for
      nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase are used in this
      study. NOS-immunoreactive (NOS-IR) neurons varied in size and were observed: (1)
      associated with nerve bundles at the hilus of the kidney, (2) in the proximity of
      the lower or middle portion of the interlobar arteries, and (3) on the wall of
      the renal pelvis. We are presenting anatomic evidence for the presence of neurons
      in the rat kidney. Their location is consistent with the existence of a
      parasympathetic innervation of the rat kidney.

PMID- 7505909
TI  - Myelin protein transcripts increase in experimental diabetic neuropathy.
AB  - A Northern blot analysis of P0 and MBP myelin protein transcripts in the sciatic
      nerve from rats with alloxan-induced diabetes at two different time points is
      described. After 5 weeks of diabetes induction, only P0 mRNA is significantly
      increased by 39%, while at 14 weeks both P0 and MBP mRNA contents are markedly
      higher than controls. Insulin treatment normalizes glycemia levels, partially
      counteracts P0 mRNA increase at both stages of diabetes and delays MBP mRNA
      increase present only in chronic animals. We suggest that increased transcript
      levels of P0 and MBP in Schwann cells may represent a higher turnover of myelin
      sheath specific proteins in diabetic syndrome, as attempt to repair the
      hyperglycemia-induced nerve damage, which is partially prevented by insulin
      treatment.

PMID- 7505910
TI  - Sudden infant death syndrome: a theory.
AB  - A hypothesis, and supporting evidence, is presented for the sudden infant death
      syndrome (SIDS). Our model is as follows. Fetal hemoglobin levels are abnormally
      elevated in SIDS infants, which contributes to a state of chronic hypoxia.
      Chronic hypoxia produces pronounced depressive effects on the respiratory system
      during slow wave sleep (a state of normal respiratory depression). These
      depressive effects are particularly manifest during that period of development in
      which slow wave sleep begins to occupy a very large percentage of total sleep
      time in infants -2-4 mo of age. A downward spiral is initiated in slow wave sleep
      such that hypoxia-induced decreases in ventilation produce more extreme hypoxia
      leading to further respiratory depression and ultimately death due to a cessation
      of respiration.

PMID- 7505911
TI  - Unexplained elevation in maternal serum alpha-fetoprotein and subsequent fetal
      loss.
AB  - OBJECTIVE: To examine the frequency and timing of fetal death and its association
      with maternal serum alpha-fetoprotein (MSAFP) levels. METHODS: Pregnancy outcomes
      were evaluated in 6927 predominantly middle-class women (83% white, 17% black)
      who had second-trimester MSAFP determinations performed in our laboratory. All
      cases of multiple gestation, preexisting fetal death, and fetal malformation were
      excluded. RESULTS: The overall fetal death rate was 13 per 1000 (n = 90). Black
      women had a higher fetal death rate than white women (35.6 per 1000 versus 8.4
      per 1000; P < .001). One hundred forty-eight women (2.1%) had an adjusted MSAFP
      multiples of the median (MoM) value of at least 2.5, which was not explained by
      multiple gestation, congenital anomaly, or preexisting fetal death. As the MSAFP
      increased, the fetal death rate increased (MoM less than 2.0, 11 per 1000; MoM 2
      2.49, 29 per 1000; MoM 2.5 or greater, 95 per 1000; P < .001). Despite the
      increased risk of fetal death in the elevated MSAFP group, most fetal deaths
      (84%) occurred in women with levels below 2.5 MoM. Furthermore, the timing of
      fetal loss was significantly different between the group less than 2.5 MoM and
      the group at or above 2.5 MoM. Fetal death occurred at or after 26 weeks in 45%
      of the women with normal MSAFP, compared with only 14% of women with high MSAFP
      (at least 2.5 MoM) (P = .023). CONCLUSIONS: Women with unexplained elevations in
      MSAFP are at increased risk for fetal loss, with most of the losses occurring in
      the second trimester. Because many of these fetal deaths occur at gestational
      ages when the neonatal survival is very low, it is unlikely that antepartum fetal
      surveillance aimed at early delivery would substantially increase fetal salvage.

PMID- 7505912
TI  - Unexplained elevations of maternal serum alpha-fetoprotein in women with
      antiphospholipid antibodies: a harbinger of fetal death.
AB  - OBJECTIVE: To determine whether unexplained elevations of maternal serum alpha
      fetoprotein (MSAFP) in women with antiphospholipid antibodies are associated with
      adverse pregnancy outcomes. METHODS: A retrospective cohort study was used to
      compare pregnancy outcomes between women with second-trimester MSAFP values equal
      to or greater than 2.5 multiples of the median (MoM) and less than 2.5 MoM. The
      cohort included 60 pregnancies in 47 women with medium to high positive levels of
      immunoglobulin (Ig) G anticardiolipin antibodies, lupus anticoagulant, or both.
      RESULTS: Thirteen pregnancies (22%) had elevated MSAFP values (median 3.6 MoM,
      range 2.5-12.6). Of these, amniotic fluid AFP was normal in seven and elevated in
      one. None of the elevated MSAFP levels were explained by fetal anomalies, current
      fetal death, multiple gestation, incorrect dates, or vaginal bleeding.
      Pregnancies with elevated MSAFP values had a significantly higher incidence of
      fetal death (eight of 13, 62%, versus three of 47, 6%) and perinatal loss (ten of
      13, 77%, versus seven of 47, 15%) than those with normal MSAFP (P < .001, Fisher
      exact test). In these women, the sensitivity and specificity of an unexplained
      elevated MSAFP level in ascertaining fetal death were 73 and 90%, respectively.
      For perinatal loss, the sensitivity was 59% and the specificity was 93%. Of the
      placentas studied, infarction occurred in eight of nine (89%) among the women
      with elevated MSAFP. CONCLUSIONS: Unexplained second-trimester elevations of
      MSAFP are common in women with antiphospholipid antibodies and are significantly
      associated with fetal loss. Abnormalities in the fetoplacental barrier are
      implicated as part of the pathophysiology of antiphospholipid antibody-mediated
      pregnancy loss.

PMID- 7505913
TI  - Phosphorylation-regulated low-conductance Cl- channels in a human pancreatic duct
      cell line.
AB  - A low-conductance Cl- channel has been identified in the apical membrane of the
      human pancreatic duct cell Capan-1 using patch-clamp techniques. Cell-attached
      channels were activated by the vasoactive intestinal polypeptide (VIP, 0.1
      mumol/l), dibutyryl-adenosine 3',5'-cyclic monophosphate (db-cAMP, 1 mmol/l), 8
      bromo adenosine 3',5'-cyclic monophosphate (8-Br-cAMP, 1 mmol/l), 3-isobutyl-1
      methyl-xanthine (IBMX, 100 mumol/l) and forskolin (10 mumol/l). No channel
      activity was observed in non-stimulated control cells. In both cell-attached and
      excised inside-out patches, the channel had a linear current/voltage relationship
      and a unitary conductance of 9 pS at 23 degrees C and 12 pS at 37 degrees C. Its
      opening probability was not voltage dependent although pronounced flickering was
      induced at negative potentials. Anionic substitution led to the selectivity
      sequence Cl- > I- >> > HCO3- > gluconate. In inside-out excised patches, the
      channel activity declined spontaneously within a few minutes. Reactivation of
      silent excised channels was achieved by adding protein kinase A (PKA, in the
      presence of ATP, cAMP and Mg2+). Conversely, active channels were silenced in the
      presence of alkaline phosphatase. The PKA-activated Cl- channel was 4,4'
      diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS, 100 mumol/l) and 4
      acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS, 100 mumol/l)
      insensitive, but was blocked by diphenylamine-2-carboxylic acid (DPC, 100
      mumol/l). These results demonstrate that the apical low-conductance Cl- channel
      in Capan-1 is regulated on-cell by VIP receptors via cAMP and off-cell by PKA and
      phosphatases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505914
TI  - Toxin pharmacology of the large-conductance Ca(2+)-activated K+ channel in the
      apical membrane of rabbit proximal convoluted tubule in primary culture.
AB  - The patch-clamp technique was used to study the toxin pharmacology of the large
      conductance Ca(2+)-activated K+ channel (BKCa) present in the apical membrane of
      rabbit proximal convoluted tubules (PCT) in primary culture. Experiments were
      performed with the inside-out configuration. This channel was very selective for
      K+ against Na+ and had a conductance of 180 pS with 140 mmol/l in the pipette and
      the bath. The action of toxins was studied on the extracellular side of the
      channel by using the pipette perfusion technique. Experimental conditions were
      140 mmol/l KCl in the pipette and 140 mmol/l NaCl in the bath. Pipette potential
      was maintained at 0 mV. Perfusion of crude venom from Leiurus quinquestriatus
      hebraeus inhibited reversibly the open probability (Po) in a concentration
      dependent fashion (IC50 = 0.8 mg/l; n = 3). The following synthetic or purified
      toxins were tested: synthetic charybdotoxin (ChTX) IC50 = 7.3 x 10(-9) M (n = 5);
      iberiotoxin (IbTX) IC50 = 5.5 x 10(-7) mol/l (n = 3); and kaliotoxin (KTX) IC50 =
      4.8 x 10(-7) mol/l (n = 3). The suppression of the six first N-terminal amino
      acids slightly reduced the affinity of ChTX (IC50 = 1.2 x 10(-8) mol/l, n = 4).
      Neither Dendroaspis polylepis venom nor purified alpha dendrotoxin modified Po
      even at high concentrations (20 mg/l and 10(-6) mol/l respectively). Apamin,
      which blocked the small-conductance K+ channel in cultured PCT, did not act on
      BKCa. These results indicate that ChTX is the most efficient known toxin against
      the epithelial BKCa in primary cultures of PCT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505915
TI  - A possible role of sarcoplasmic Ca2+ release in modulating the slow Ca2+ current
      of skeletal muscle.
AB  - Ca2+ channels are regulated in a variety of different ways, one of which is
      modulation by the Ca2+ ion itself. In skeletal muscle, Ca2+ release sites are
      presumably located in the vicinity of the dihydropyridine-sensitive Ca2+ channel.
      In this study, we have tried to investigate the effects of Ca2+ release from the
      sarcoplasmic reticulum on the L-type Ca2+ channel in frog skeletal muscle, using
      the double Vaseline gap technique. We found an increase in Ca2+ current amplitude
      on application of caffeine, a well-known potentiator of Ca2+ release. Addition of
      the fast Ca2+ buffer BAPTA to the intracellular solution led to a gradual decline
      in Ca2+ current amplitude and eventually caused complete inhibition. Similar
      observations were made when the muscle fibre was perfused internally with the
      Ca2+ release channel blocker ruthenium red. The time course of Ca2+ current
      decline followed closely the increase in ruthenium red concentration. This
      suggests that Ca2+ release from the sarcoplasmic reticulum is involved in the
      regulation of L-type Ca2+ channels in frog skeletal muscle.

PMID- 7505917
TI  - Automatic mode change.

PMID- 7505916
TI  - [Future treatment of stroke. Brain injury can be reduced with drugs].
AB  - In all likelihood, ischaemia results in parallel damage to nerve cells and the
      microvasculature. The death of nerve cells--after ischaemia of extended duration-
      is followed by secondary damage to glial cells and the microvasculature. Several
      pharmacological agents have been shown experimentally to reduce cerebral
      infarction by improving the microcirculation or microvascular function, and
      reducing inflammatory reactions. However, pharmacological therapy must be started
      within six hours after onset.

PMID- 7505918
TI  - Interatrial conduction in patients undergoing AV stimulation: effects of
      increasing right atrial stimulation rate.
AB  - To evaluate the frequency of spontaneous or rate dependent interatrial blocks,
      the interatrial conduction time (IACT) was studied on 100 consecutive patients
      (mean age 78.3 +/- 7.8 years) during a transvenous dual chamber pacemaker
      implant. The spontaneous interatrial conduction time (SIACT) was measured from
      the intrinsic deflection (ID) of the unipolar right atrial signal to the ID of
      the left atrial signal recorded in a bipolar way by an esophageal lead. The paced
      interatrial conduction time (PIACT) was measured from the stimulus artifact to
      the left atrial ID, when the atrium was paced at a slightly higher rate than the
      spontaneous rate and during incremental atrial pacing. From these measurements,
      the maximum increase of PIACT (MIPIACT) was deduced. In this elderly population,
      the PIACT was similar (117 +/- 26.9 msec) to the data in the literature. However,
      there were large interindividual variations that were also found in SIACT. We
      found a close correlation between SIACT and PIACT (P < 0.0001). PIACT was on
      average 50 msec longer than SIACT. SIACT increased with age (P < 0.03). The
      MIPIACT was 15.3 +/- 15.2 msec. In the majority of patients, the MIPIACT was > 10
      msec, and even reached 90 msec in one patient. MIPIACT was longer in patients
      with a PIACT exceeding 110 msec (P < 0.004). Based on IACT alone, the AV interval
      must be lengthened on average by 50 msec when changing from atrial tracking
      ventricular pacing to atrial pacing-ventricular pacing, but large individual
      differences must be kept in mind. Elderly people should probably have a longer AV
      delay.

PMID- 7505919
TI  - Coronary artery bypass in patients with previously placed implantable
      defibrillators.
AB  - Four patients with previously placed implantable defibrillators required coronary
      revascularization several years after the original device was inserted. Three
      patients had a conventional system of epicardial patches and leads, and one
      patient had a nonthoracotomy system placed. All four patients were successfully
      revascularized without evidence of perioperative infarction or significant
      morbidity. The patient with the nonthoracotomy device did require manipulation of
      the endocardial lead at a separate setting. This limited experience suggests that
      patients needing revascularization after placement of an implantable
      defibrillator can be successfully bypassed.

PMID- 7505920
TI  - Cardioversion, defibrillation, and overdrive pacing of ventricular arrhythmias:
      the effect of moricizine in dogs with sustained monomorphic ventricular
      tachycardia.
AB  - The purpose of this investigation is to define whether the antiarrhythmic drug
      moricizine has beneficial or adverse effects on currently used antitachycardia
      and antifibrillatory devices. These studies were performed in a dog model of
      sustained monomorphic ventricular tachycardia (VT). In 11 dogs, the left anterior
      descending artery and all surrounding epicardial collateral feeder vessels were
      ligated. Defibrillator patches were implanted and the dogs were allowed to
      recover. After a 7-day recovery period, effective refractory period (ERP), end
      diastolic threshold (EDT), VT induction, and VT and ventricular fibrillation (VF)
      termination data were collected before and after moricizine infusion (2 mg/kg).
      In this experimental model, moricizine caused the following electrophysiological
      changes: a prolongation of the ERP from 173 +/- 14 to 182 +/- 15 (P < 0.02) with
      no significant effect on the EDT for pacing; a prolongation of the VT cycle
      length from 175 +/- 18 to 201 +/- 23 msec (P < 0.003); an increased cycle length
      required for overdrive pacing from 136 +/- 20 to 157 +/- 22 msec (P < 0.01); no
      effect on the energy required to cardiovert VT; an increase in the defibrillation
      threshold from 7.5 +/- 4 to 9.4 +/- 4 joules (P < 0.006) and; in 5 of the 8 dogs
      with VT, the VT could be initiated with somewhat less aggressive stimulation.
      Significant beneficial electrophysiological physiological effects were noted on
      the VT cycle length, including a proportionately prolonged overdrive pacing cycle
      length for VT termination.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505921
TI  - Intravenous adenosine reveals intermittent preexcitation by direct and indirect
      effects on accessory pathway conduction.
AB  - In some patients with accessory pathways preexcitation occurs intermittently
      during sinus rhythm. In these patients the antegrade refractory period of the
      accessory pathway may either exceed the sinus cycle length under some
      circumstances, or conduction block in the accessory pathway may be variable. The
      ability of intravenous adenosine to unmask intermittent preexcitation was
      determined in patients with intermittent preexcitation but absent preexcitation
      at the time of study. Six patients undergoing assessment of the Wolff-Parkinson
      White syndrome received incremental doses of intravenous adenosine (3, 6, and 12
      mg). Adenosine administration was repeated in three patients after intravenous
      beta blockade (propranolol 0.2 mg/kg). Adenosine unmasked preexcitation in all
      patients. P delta intervals with preexcited beats were substantially shorter than
      resting PR intervals in all cases (range 40-80 msec shorter). In 4/6 patients
      preexcitation was seen early, coincident with the onset of atrioventricular nodal
      block. In 4/6 patients preexcitation was seen late during the secondary sinus
      tachycardia that follows the direct cardiac effects of adenosine. Two patients
      exhibited early preexcitation and late preexcitation. Beta blockade failed to
      prevent early preexcitation (2/2 patients) but abolished preexcitation related to
      sinus tachycardia (3/3 patients). Early preexcitation, coincident with the onset
      of AV nodal block, suggests a direct effect of adenosine on accessory pathway
      conduction. Late preexcitation, occurring during secondary sinus tachycardia, and
      abolished by beta blockade, suggests enhanced accessory pathway conduction due to
      sympathetic activation.

PMID- 7505922
TI  - Prognostic implications of loss of late potentials following acute myocardial
      infarction.
AB  - The prognosis of patients following myocardial infarction is adversely affected
      by the finding of late potentials at the time of hospital discharge. Loss of late
      potentials has been previously reported during serial testing during the first
      year after infarction, but it is not known whether such patients remain at risk
      of arrhythmic events. This study prospectively followed 243 patients after
      myocardial infarction. Late potentials were observed in 92 patients (group I) at
      the time of hospital discharge. Of these patients, 23 no longer had late
      potentials at 6-week follow-up and 8 had had an arrhythmic event (sudden death or
      ventricular tachycardia). In patients with loss of late potentials, overall QRS
      duration had decreased from 109 +/- 11 msec at discharge to 104 +/- 11 msec (P <
      0.01), terminal QRS voltage rose from 15 +/- 4 microV to 31 +/- 9 microV (P =
      0.001), and late potential duration fell from 42 +/- 6 msec to 28 +/- 6 msec (P =
      0.001) at the 6-week study. Predictors of loss of late potentials were: initial
      duration of the QRS duration (P < 0.001) and terminal voltage (P < 0.005); non-Q
      wave infarction (P < 0.001); and being a male (P < 0.05). After the 6-week
      assessment, 11 additional arrhythmic events occurred during median follow-up of
      31 months. The risk of arrhythmic events was similar in patients with loss of
      late potentials and those who retained late potentials in group I (9% vs 11%, P =
      NS) but significantly greater than patients with no late potentials at discharge
      (group II, 2%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505923
TI  - Single physician approach to radiofrequency catheter ablation in patients with
      supraventricular tachycardia.
AB  - The minimal requirements for safe and effective performance of catheter ablation
      using radiofrequency current are still unclear. To determine the feasibility and
      safety of single physician approach to catheter ablation of supraventricular
      tachycardia substrate using radiofrequency energy, the results of the ablation
      procedure in 52 consecutive patients were evaluated. The procedures were
      performed during 1 year by the same physician and nurse. Twenty-one patients had
      selective atrioventricular (AV) nodal pathway ablation and 31 patients had
      accessory AV pathway ablation. Forty-eight patients (89%) had the diagnostic and
      the ablative procedure during the same electrophysiological test. In the 21
      patients with AV nodal reentrant tachycardia, all had successful selective
      ablation of the fast (13) or the slow (8) pathways. Eight patients had recurrence
      of the clinical tachycardia and had a successful reablation. No patient developed
      complete AV block or other significant complications. The mean fluoroscopy time
      during the procedure was 16.0 +/- 8.6 minutes. In the eight patients with Wolff
      Parkinson-White syndrome, all concealed accessory pathways were successfully
      ablated with a mean fluoroscopy time of 30.0 +/- 27.9 minutes. Two patients had
      recurrence of the conduction through the accessory pathway and had a successful
      reablation. Eighteen of 19 patients with a single overt accessory pathway had
      successful ablation, with a fluoroscopy time of 22.7 +/- 20.6 minutes. Three
      patients had an early recurrence of the conduction through the accessory pathway,
      reablation was successful in two of them. Ten accessory pathways were ablated in
      four patients with multiple pathways during nine procedures. Only two patients
      developed minor peripheral vascular complications.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7505924
TI  - Prediction of arrhythmic events after acute myocardial infarction using two
      methods for late potentials recording.
AB  - One hundred consecutive patients recovering from an acute myocardial infarction
      underwent, prior to home discharge, signal-averaged electrocardiography (ECG),
      left ventriculography, and 24-hour Holter ECG recording. The signal-averaged ECG
      was recorded and analyzed using two procedures: the orthogonal bipolar XYZ lead
      configuration with a bidirectional filter; and a precordial unipolar lead
      configuration with a nonrecursive digital filter. An abnormal signal-averaged ECG
      was seen in 40% of patients with the XYZ system and in 30% of patients in the
      precordial method, abnormal ejection fraction (< 40%) in 24% of patients and high
      grade ectopy activity in 22%. During the 24-month follow-up period, 12 patients
      (12%) had an arrhythmic event defined as either sudden death (11 patients) or
      sustained ventricular tachycardia (1 patient). Neither the signal-averaged ECG
      with the XYZ configuration, the abnormal ejection fraction, nor the high grade
      ectopy were able to statistically predict a higher arrhythmic event rate. The
      signal-averaged ECG with the precordial configuration was able to statistically
      predict a higher arrhythmic event rate, P < 0.03; odds ratio = 3.96. The
      combination of the orthogonal XYZ configuration signal-averaged ECG with the
      ejection fraction (P < 0.01, odds ratio = 7.33), or with ejection fraction and
      Holter monitoring (P < 0.06, odds ratio = 6.17) was able to predict a higher
      arrhythmic event rate. The combination of the precordial configuration signal
      averaged ECG with the ejection fraction (P < 0.002, odds ratio = 14.4), or with
      ejection fraction and Holter monitoring (P < 0.06, odds ratio = 10) was able to
      better predict a higher arrhythmic event rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505925
TI  - Influence of a third extrastimulus in defining effective drug therapy during
      serial electrophysiological testing.
AB  - Many electrophysiology laboratories use three extrastimuli in all patients with
      ventricular tachyarrhythmias during antiarrhythmic drug testing, regardless of
      the mode of arrhythmia induction in the baseline state. The purpose of this study
      was to compare this pacing protocol (full protocol) with a protocol in which
      three extrastimuli were only used during drug tests, if they were required in the
      baseline state for arrhythmia induction (limited protocol). There were 181
      electrophysiology tests performed on 69 patients with ventricular
      tachyarrhythmias that were retrospectively analyzed. In all studies the full
      protocol was used, but the results of stimulation were also analyzed assuming the
      limited protocol had been used. In the baseline state, sustained ventricular
      tachyarrhythmias were reproducibly inducible with one or two extrastimuli in 38
      (55%) patients. Of these patients, six (16%) achieved a drug efficacy prediction
      using the full protocol versus 15 (39%) patients using the limited protocol (P <
      0.001). In all 69 patients, the drug response rate increased from 25% to 38% (P <
      0.01) using the limited protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505926
TI  - A new approach to percutaneous subclavian venipuncture to avoid lead fracture or
      central venous catheter occlusion.
AB  - Pacemaker and defibrillator leads and central venous catheters placed by commonly
      recommended techniques have been found to pass through the subclavius muscle, the
      costocoracoid ligament, or the costoclavicular ligament before entering veins
      medial to the first rib. Entrapment by these soft tissues subjects leads and
      catheters to stresses imposed by movements of the ipsilateral upper extremity.
      Accordingly, a new approach has been developed that introduces the lead or
      catheter into the subclavian vein near the lateral border of the first rib. This
      placement avoids soft tissue entrapment and may extend the longevity of leads and
      catheters.

PMID- 7505927
TI  - Delayed response to radiofrequency ablation of accessory connections.
AB  - This article summarizes delayed interruption in anomalous conduction through
      accessory connections following radiofrequency ablation attempts in three
      patients. The time course of the delayed interruption in accessory connection
      conduction suggests that such an effect is unlikely to occur after the first week
      following unsuccessful radiofrequency ablation.

PMID- 7505928
TI  - Radiofrequency ablation therapy in three patients with paroxysmal atrial
      tachycardia.
AB  - Radiofrequency ablation therapy was performed in three patients with paroxysmal
      atrial tachycardia. There were two females and one male, aged 80, 63, and 75
      years, respectively. All three patients had induction of sustained atrial
      tachycardia. The tachycardia could be terminated by overdrive atrial pacing or
      atrial premature stimulation; it could also be terminated by intravenous bolus of
      adenosine triphosphate. In all three patients, there was no fragmented atrial
      electrograms recorded within the right atrium, and there was no ventriculo-atrial
      conduction during ventricular pacing. The earliest atrial activation during
      tachycardia in these three patients was registered, respectively, at a site
      slightly posterior and inferior to the His-bundle recording site, at the anterior
      superior border of Koch's triangle slightly posterior to the His-bundle recording
      site, and at the mid-lateral aspect of the right atrium over the crista
      terminalis at the junction of right atrial appendage and sinus venarum.
      Radiofrequency current was delivered to the site of the earliest atrial
      activation during tachycardia through a 4-mm tip electrode catheter. It resulted
      in termination of tachycardia and ablation of the tachycardia focus. Follow-up
      observation over a period of 16, 15, and 4 months, respectively, in these three
      patients showed no recurrence of tachycardia. A repeat electrophysiological study
      was performed 52 and 63 days after ablation in two patients and revealed no
      induction of atrial tachycardia.

PMID- 7505929
TI  - Doppler echocardiographic assessment of the hemodynamic benefits of rate adaptive
      AV delay during exercise in paced patients with complete heart block.
AB  - To determine if rate adaptation of the atrioventricular (AV) delay (i.e.,
      linearly decreasing the AV interval for increasing sinus rate) improves exercise
      left ventricular systolic hemodynamics, we performed paired maximal semi-upright
      bicycle exercise tests (EXTs) on 14 chronotropically competent patients with dual
      chamber pacemakers. Nine patients with complete AV block (CAVB) and total
      ventricular pacing dependence during exercise comprised the experimental group.
      Pacemakers in these patients were programmed randomly to rate adaptive AV delay
      (AVDR) for one EXT and fixed AV delay (AVDF) for the other EXT. AVDF was 156
      msec; AVDR decreased linearly from 156-63 msec from rates of 78-142 beats/min.
      The other five patients had intact AV conduction and comprised the control group
      who were exercised in identical fashion while their pacemakers were inhibited
      throughout exercise to assure reproducibility of hemodynamic measurements between
      EXTs. Cardiac hemodynamics were calculated using measured Doppler
      echocardiographic systolic aortic valve flows recorded suprasternally with an
      independent 2-MHz Doppler transducer during a graded ramp exercise protocol. For
      analysis, exercise was divided into four phases to compare Doppler measurements
      at submaximal and maximal levels of exercise: rest, early exercise (1st stage),
      late exercise (stage preceding peak), and peak. Patients achieved statistically
      similar heart rates between EXTs at each phase of exercise. Although at lower
      levels of exercise cardiac hemodynamics did not differ, experimental patients
      (with CAVB) showed a statistically significant benefit to cardiac output at peak
      exercise with heart rates of 129 +/- 13 beats/min (AVDR: 9.4 +/- 2.8 L/min; AVDF:
      8.2 +/- 2.6 L/min, P = 0.002), stroke volume (AVDR: 74.1 +/- 25.6 mL; AVDF: 64.3
      +/- 24.4 mL, P = 0.0003), and aortic ejection time (AVDR: 253.3 +/- 35.7 msec;
      AVDF: 226.7 +/- 35.0 msec, P = 0.002). Duration of exercise, peak rate pressure
      product, peak aortic flow velocities, and acceleration times did not differ. In
      contrast, control group patients (intact AV conduction throughout exercise)
      showed no statistical differences between any hemodynamic parameters measured at
      any phase of exercise from the first to second exercise test. These data
      demonstrate that systolic cardiac hemodynamics measured echocardiographically at
      the high heart rates achieved with peak exercise are improved with AVDR compared
      to AVDF in chronotropically competent patients with complete AV block. This is
      due primarily to improved stroke volume and a longer systolic ejection time with
      AV delay rate adaptation.

PMID- 7505931
TI  - Disaster recovery.

PMID- 7505930
TI  - Dual chamber, rate adaptive pacing in patients with paroxysmal supraventricular
      tachyarrhythmias: protective measures for rate control.

PMID- 7505932
TI  - Sudden cardiac death and national health.

PMID- 7505933
TI  - Premature ICD battery depletion due to a defective lead adapter component:
      usefulness of extensive data logging.
AB  - Described herein is the usefulness of extensive data logging of third generation
      ICDs in a patient with premature ICD battery depletion due to a defective
      pace/sensing lead component. Due to noise artifacts, VT/VF detections occurred
      leading to inappropriate patient shock discharges and 2,267 internal charge dumps
      within 2 weeks. During manual manipulations at the ICD site, real-time
      intracardiac electrocardiogram and event markers revealed noise artifacts that
      were interpreted as VT/VF. Radiography confirmed slight movement of the
      pace/sensing lead pin out of the Y-adapter. Therefore, the design of adapter
      systems without screw fixation should be reviewed to ensure lead integrity. In
      the case of sudden increases in VT/VF recognition, defective sensing components
      must be considered.

PMID- 7505934
TI  - Resolution of atrial standstill in a child with myocarditis.
AB  - Atrial standstill is a rare disorder usually seen in adults with extreme
      myocardial disease. Etiologies described in the literature have included muscular
      dystrophy, familial amyloidosis, and rarely myocarditis. These etiologies usually
      lead to permanent atrial standstill and require ventricular pacing. We present a
      case of an 11-year-old black female who developed atrial standstill secondary to
      biopsy proven acute necrotizing myocarditis. Absence of atrial function was
      confirmed by surface electrocardiogram, echocardiogram, and an invasive
      electrophysiology study. Atrial function returned within 3 days of initiation of
      methyl-prednisolone. In cases of atrial standstill due to myocarditis, a delay in
      the placement of a permanent pacemaker with or without a trial of
      methylprednisolone may prove beneficial.

PMID- 7505935
TI  - Radiofrequency catheter ablation of sinus node reentrant tachycardia.
AB  - Sinus node reentrant tachycardia is a relatively uncommon (5%-15%) form of
      recurrent paroxysmal supraventricular tachycardia (SVT). We describe a case of
      symptomatic sinus node reentrant tachycardia in a 67-year-old male with ischemic
      heart disease, congestive heart failure, and depressed ventricular function.
      Adenosine administered during an electrophysiology study caused prolongation of
      the tachycardia cycle length due to atrial cycle length prolongation (without
      atrio-His prolongation) prior to tachycardia termination. Right atrial mapping
      revealed the earliest site of atrial activation in the high lateral right atrium
      just below the superior vena cava. Low energy (10 and 20 W) radiofrequency
      lesions were applied at this site with termination of the tachycardia within 3
      seconds of radiofrequency energy delivery. Tachycardia could not be reinduced
      after delivery of the radiofrequency lesions. The sinus node function immediately
      and 6 weeks after radiofrequency catheter ablation remained normal and the
      patient was without clinical recurrence of SVT. Mapping of sinus node reentrant
      tachycardia and elimination of the reentrant circuit with radiofrequency catheter
      ablation is possible without causing sinus node dysfunction. Adenosine causes
      prolongation of the atrial cycle length followed by termination of sinus node
      reentrant tachycardia.

PMID- 7505936
TI  - Chest PA and lateral.

PMID- 7505937
TI  - Modification of pacemaker lead retrieval techniques.

PMID- 7505938
TI  - Undesirable mode switching with a Telectronics 1250 META DDDR pacemaker.

PMID- 7505939
TI  - Oral absorption of FK506 in rats.
AB  - The oral absorption of FK506 in solid dispersion formulation was studied in rats.
      The obtained area under the concentration versus time curve (AUC) increased in a
      nonlinear fashion with a small dose-dependent increase in the peak blood
      concentrations (Cmax). The peak concentration time (Tmax) was observed within 30
      min after administration in all dosing groups (1-10 mg/kg) with or without
      feeding, whereas the oral absorption of FK506 was reduced to about 50% by gavage
      at a dose of 1 mg/kg. Participation of first-pass elimination was suggested by
      comparing the blood levels after infusion via the portal vein with those after
      infusion via the femoral vein. Further, in an in vitro stability study and an in
      situ loop absorption study, FK506 was fairly stable in the gastrointestinal juice
      and was absorbed predominantly from the upper part of the small intestine.

PMID- 7505941
TI  - [Palliative treatment of esophageal neoplastic stenoses with self-expanding
      metallic stents].
AB  - Thirty Strecker nickel-titanium self-expanding metallic stents were implanted in
      20 patients with esophageal strictures and inoperable neoplasms in the
      Departments of Radiology of the University School of Medicine of Ferrara, Genoa,
      Novara and Rome, from March 1992 to April 1993; follow-up ranged 1 to 13 months.
      Thanks to the stents, esophageal strictures could be dilated, significantly
      reducing dysphagia and allowing the patients to return on to a solid diet.
      Radiological and endoscopic exams proved the efficacy of the stents in all but 2
      patients in whom the tumors had invaded the stent lumen and caused obstruction.
      In all cases the stents were highly biocompatible and well tolerated. Neither
      major complications, such as perforation or bleeding, were observed, nor minor
      ones, such as fever or migration from the site of implant, which may occur with
      plastic prostheses. To conclude, self-expanding metallic stents used in clinical
      trials for 13 months proved an effective method in the palliative treatment of
      malignant esophageal strictures.

PMID- 7505940
TI  - Stabilization of lyophilized porcine pancreatic elastase.
AB  - Porcine pancreatic elastase, a well-characterized serine protease, has been used
      as a model to assess the effects of excessive humidity on solid-state stability
      of the lyophilized protein. Elastase lyophilized without excipients retained full
      activity immediately after freeze-drying but became denatured upon continued
      storage at 40 degrees C, 75% relative humidity. The extent of inactivation could
      be monitored through assays of amidolytic activity, as well as through changes in
      the circular dichroism (CD) and fluorescence spectra. Differential scanning
      calorimetry (DSC) was employed as a means of screening potential stabilizing
      additives; based on the results, sucrose and dextran 40 were selected for further
      evaluation. Both additives were effective in preventing denaturation. Possible
      mechanisms for the denaturation and stabilization of elastase are discussed.

PMID- 7505942
TI  - [Hypermedia software for teaching anatomy of the upper abdomen with computerized
      tomography and magnetic resonance].
AB  - The authors have developed a hypermedia program for creating a tutorial of CT and
      MR anatomy of the upper abdomen. The program was created on a Mcintosh computer,
      with the Supercard software: it is made up of a series of windows, each of them
      containing images, texts, schematic representations and sound. Moreover, each
      window contains buttons which are activated with the mouse and allow different
      kinds of function, all created by the authors to be displayed. In particular,
      navigation buttons allow the users to move in the program either sequentially or
      non-linearly, according to their needs. The possibility of obtaining information
      and schematic representations is given by specific buttons. There are also
      multiple buttons hidden in the images which, when activated, allow the name of
      the selected organ to be displayed. In conclusion, this program can be especially
      helpful since it allows different data sets to be integrated to provide the user
      with complete information. Moreover, the program allows learning to be
      controlled, that is the user to be informed on timing and methods for more
      effective studying.

PMID- 7505943
TI  - [Palliative treatment of neoplastic stenosis of the recto-sigmoid junction with
      Strecker self-expanding stent. Description of a case].

PMID- 7505944
TI  - Inhibition by methylene blue of the L-arginine metabolism to L-citrulline coupled
      with nitric oxide synthesis in cultured endothelial cells.
AB  - The effect of methylene blue on the metabolism of L-arginine to L-citrulline
      coupled with nitric oxide synthesis in cultured endothelial cells was
      investigated. The addition of the calcium ionophore ionomycin (10(-8)-10(-5) M)
      to endothelial cells stimulated L-citrulline formation from L-arginine. Ionomycin
      stimulated L-citrulline formation was inhibited by NG-nitro-L-arginine (10(-6)
      10(-4) M), a potent inhibitor of nitric oxide synthase. These results indicate
      that ionomycin-stimulated L-citrulline formation was coupled to nitric oxide
      synthesis. Therefore, L-citrulline formation from L-arginine was used as a marker
      for nitric oxide synthesis. Methylene blue (10(-4)-10(-3) M) inhibited ionomycin
      stimulated L-citrulline formation in bovine aortic endothelial cells. Moreover,
      the formation of L-citrulline by the particulate fraction obtained from bovine
      cultured endothelial cells was also inhibited by methylene blue concentrations in
      excess of 10(-5) M. Although the addition of methylene blue to various tissues
      has been reported to release superoxide anions (Wolin et al., 1990; Marczin et
      al., 1992), inhibition of L-citrulline formation by methylene blue was not
      affected by the presence of superoxide dismutase (100 micrograms/mL) in either
      cultured endothelial cells or the particulate fraction. These findings suggest
      that methylene blue is a direct inhibitor of nitric oxide synthase in bovine
      aortic endothelial cells.

PMID- 7505945
TI  - [Natural follow-up of prostate cancer and consequences for early detection].
AB  - The natural history of prostatic cancer has been regarded as unpredictable for a
      long period of time. The discrepancy between histologically identifiable (50%)
      and clinically diagnosed carcinomas (8%) led to the term of 'latent' prostatic
      cancer and to a considerable diagnostic and therapeutic dilemma. Based on our
      previous studies showing that biological aggressiveness of prostatic cancer is a
      direct function of tumor volume and that tumor volume and serum-PSA are
      proportional, we evaluated two basically different groups of patients. The first
      group consisted of 43 patients with untreated carcinomas of the prostate followed
      with serial PSA determinations. The exponential (log-linear) rise in PSA led us
      to the conclusion of an exponential tumor growth rate. The doubling time of organ
      confined tumors was three to four years and became shorter with higher clinical
      stages and poorly differentiated histological grades. The second group consisted
      of 139 patients who underwent cystoprostatectomy for bladder cancer and had no
      evidence for simultaneously identifiable prostatic cancer. In 55 Patients (40%)
      unsuspected prostatic cancer was found in the specimen; the volume distribution
      of these carcinomas was exponential. Eleven of the 139 men (7.9%) had a prostatic
      cancer > or = 0.5 cc, corresponding to the 8%-risk for a man being diagnosed
      within his lifetime with a clinically significant carcinoma of the prostate. We
      conclude that the other 44 carcinomas < 0.5 cc will never reach clinical
      significance due to their small size and their long doubling time; in this sense
      they can be considered 'latent'.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7505946
TI  - Diagnosis of urinary tract infection by urine microscopy using a disposable
      counting chamber.
AB  - Routine urinalysis is performed as a screening test for urinary tract infection
      (UTI), but is not very reliable. We assessed the usefulness of microscopic
      examination of unspun urine using a disposable slide with counting chambers for
      the diagnosis of UTI caused by a variety of species of bacilli. One hundred and
      seventy-two urine samples were obtained from 113 subjects (60 male and 53
      female), including 84 inpatients, aged 20-96 years. The urine samples were
      examined for bacteriuria and pyuria using a counting chamber, and the reliability
      of this method in predicting significant bacteriuria defined by routine urine
      culture and Gram stain of urine smears was analyzed. Significant bacteriuria was
      diagnosed in 68 urine samples, including 34 from indwelling catheters, from 52
      patients mostly having underlying diseases. Only 12 of the positive urine samples
      contained E. coli, with a variety of other bacilli including cocci found in the
      rest. The counting chamber method detected bacteriuria in 64 of these 68 positive
      samples (sensitivity = 94%). Specificity was 88%. While the sensitivity and
      specificity of pyuria (WBC > 10 microliters-1) were 79 and 71%, respectively,
      both sensitivity and negative predictive value were as high as 97% when
      bacteriuria or pyuria was present. We demonstrated that urine microscopy on a
      disposable counting chamber is a simple, sensitive and time- and cost-saving
      method for the diagnosis of UTI caused by a variety of bacterial species
      including cocci.

PMID- 7505947
TI  - Effect of preoperative inflammation of the wound bed on survival of skin flaps in
      rats.
AB  - Pedicled dorsal flaps were raised and resutured on the backs of 20 rats. Aseptic
      inflammation of the bed of the wound flap was induced one week before the
      operation in 10 rats by scratching with a needle; the other 10 acted as controls.
      A week after the operation the extent of necrosis was estimated by computer
      assisted planimetry. Blood flow in the four quarters of the flap and in normal
      skin was estimated using the microsphere technique. A larger mean area of the
      skin flaps survived in rats in which the wound bed had been scratched (71%)
      compared with the controls (61%) (p < 0.05); blood flow in the flaps was also
      higher (p < 0.0005). We conclude that the most likely explanation for these
      results was preoperative angiogenesis in the wound bed.

PMID- 7505948
TI  - The complex lesions: problems in the adult survivors.

PMID- 7505949
TI  - [Problems of non-invasive diagnosis of congenital heart defects in adulthood].
AB  - Non-invasive assessment of adult congenital heart disease comprises Doppler
      echocardiography and magnetic resonance imaging (MRI). Doppler echocardiography
      represents the modality of choice to perform serial follow-up and MRI is used as
      supplementary method in the diagnosis of congenital heart disease in adults. The
      spectrum of congenital heart disease in adults encompasses (a) uncorrected and
      newly detected defects; (b) palliatively corrected and totally corrected defects.
      In general, diagnostic modalities must be able to fulfill the following
      requirements: (a) sequential morphologic analysis; (b) assessment of
      hemodynamics. Sequential morphologic analysis using 2-dimensional
      echocardiography includes determination of the situs of the atria, atrio
      ventricular and ventriculo-arterial connections. Non-invasive assessment of
      hemodynamics is performed with the Doppler technique and comprises diagnosis and
      quantitation of (a) (residual) shunt lesions, (b) valvular regurgitation and (c)
      valvular, subvalvular, supravalvular and infundibular stenosis as well as
      pressure gradients across anastomoses and intracavitary or intercavitary
      gradients, respectively. Pulmonary vascular resistance cannot be assessed
      quantitatively by Doppler. However, the determination of the end-diastolic
      gradient between the pulmonary artery and the right ventricle in the presence of
      pulmonic regurgitation allows estimation of the diastolic pulmonary artery
      pressure.

PMID- 7505950
TI  - [Failing B7 costimulation engenders a peripheral clonal T-cell anergy in a human
      antigen-specific model].

PMID- 7505951
TI  - Molecular medicine: a primer for clinicians. Part IV: Cystic fibrosis and the
      power and limitations of molecular medicine.
AB  - Cystic fibrosis (CF) is among the most common genetic diseases in caucasians of
      Northern European ancestry. The cloning of the gene responsible for cystic
      fibrosis, the characterization of the product of the gene and identification of
      mutations occurring in CF patients are excellent examples of the potential
      clinical utility of molecular medicine. The ethical issues associated with the
      ability to identify carriers of CF mutations highlight the magnitude of the
      questions molecular medicine raises.

PMID- 7505952
TI  - The Met proto-oncogene mesenchymal to epithelial cell conversion.
AB  - Coexpression of the human Met receptor and its ligand, hepatocyte growth
      factor/scatter factor (HGF/SF), in NIH 3T3 fibroblasts causes the cells to become
      tumorigenic in nude mice. The resultant tumors display lumen-like morphology,
      contain carcinoma-like focal areas with intercellular junctions resembling
      desmosomes, and coexpress epithelial (cytokeratin) and mesenchymal (vimentin)
      cytoskeletal markers. The tumor cells also display enhanced expression of
      desmosomal and tight-junction proteins. The apparent mesenchymal to epithelial
      conversion of the tumor cells mimics the conversion that occurs during embryonic
      kidney development, suggesting that Met-HGF/SF signaling plays a role in this
      process as well as in tumors that express both epithelial and mesenchymal
      markers.

PMID- 7505953
TI  - Sensory and autonomic innervation of the facet joint in the rat lumbar spine.
AB  - The presence of sensory and autonomic nerves in the synovial membrane of the
      lumbar facet joint in rats was investigated by immunohistochemistry. Substance P
      and calcitonin gene-related peptide immunoreactivities, representing sensory
      nerves, were observed as varicose fibers in the synoviocyte layer. The fibers
      were predominantly nonvascular. The autonomic innervation was identified by the
      presence of neuropeptide Y- and tyrosine hydroxylase-positive fibers. Most of
      these fibers were found adjacent to or within blood vessel walls.
      Immunoreactivity to vasoactive intestinal polypeptide was seen in varicose nerve
      terminals in the synoviocyte layer, mostly unrelated to blood vessels. There is
      accumulating evidence of an involvement of both the sensory and sympathetic
      nervous systems in inflammatory joint disease. The neuropeptides now identified
      in lumbar facet joints may prove to play a significant role in the pathogenesis
      of low-back pain.

PMID- 7505954
TI  - Mixing incompatibilities and toxic exposures.
AB  - A number of consumer and commercial products may react, upon inappropriate
      mixing, to produce substances of greater toxicity than the starting materials.
      Consumer product mixing incompatibilities have been well documented and warning
      labels appear on high-risk products. In industry, a wider array of potential
      mixing incompatibilities exists and includes potential accidents in chemical
      storage and hazardous material handling. Emergency response personnel are a group
      who often deal with inadvertent mixing related to transportation and other
      hazardous materials incidents. This article assembles some better-known examples
      of toxicologically significant exposures resulting from inadvertent or deliberate
      mixing of incompatible materials.

PMID- 7505955
TI  - [Nerve supply to the anterior cruciate ligament and cruciate ligament allograft].
AB  - To confirm the innervation of the anterior cruciate ligament and anterior
      cruciate allograft the anterior cruciate ligament was grafted allogenic and deep
      freeze preserved, in 12 white New Zealand rabbits. After removal from the donor
      animal the ligaments and pertaining bone tissue were placed in deep freeze at -90
      degrees C for 72 hours. The grafts were fixed in the receiving animal by means of
      transosseous wire sutures. The non-operated contralateral anterior cruciate
      ligament served as control. Follow-up examinations were performed after 3, 6, 12,
      24, 36 and 52 weeks. Immunohistochemical methods were employed to examine newly
      ingrown nerve fibres. Monoclonal antibodies against neurofilaments (to identify
      rapid conducting mechanoreceptive afferent A fibres) were used, as well as
      substance P (to identify slow conducting nociceptive afferent C fibres) and
      thyrosine hydroxylase (for the identification of vasomotor efferent C fibres). In
      the control ligaments we found an abundant amount of nerve fibres of all three
      kinds, each of these having its own typical distribution pattern. The fibres were
      mainly subsynovial, in some cases however also localised in the interfascicular
      connective tissue septae. At specialised end organs we could only identify
      Ruffini's corpuscles. No nerve fibres were found in the cruciate ligament
      allografts after 3 weeks, but an initial few fibres showed up after 6 weeks.
      After 12 weeks individual nerve fibres of all 3 kinds became noticeable, and
      after 24 weeks all three kinds of fibres were abundantly represented. No
      specialised end organs were found in the allografts.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7505956
TI  - Modifying influence of prior treatment with toxic agents on induction of
      preneoplastic and neoplastic lesions in a medium-term multi-organ carcinogenesis
      bioassay.
AB  - The modifying potential of prior administration of toxic agents was investigated
      in our multi-organ carcinogenesis model using male F344/DuCrj rats with the aim
      of assessing the link between tissue damage and initiation. Animals were
      administered one of four toxic agents for 8 wk, and then treated with N
      diethylnitrosamine (DEN, 100 mg/kg body weight (b.w.), intraperitoneally (i.p.),
      single injection), N-methylnitrosourea (MNU, 20 mg/kg b.w., i.p., four times
      during wk 9 and 10), and dihydroxy-di-N-propylnitrosamine (DHPN, 0.1% in drinking
      water, during wk 11 and 12) for multi-organ carcinogenesis. All surviving rats
      were killed at the end of wk 36, and the major organs carefully examined for
      preneoplastic and neoplastic lesion development. Immunohistochemical
      demonstration of glutathione S-transferase placental form (GST-P) positive foci
      was also performed to facilitate quantitative assessment of liver lesion
      development. D-galactosamine (300 mg/kg b.w., i.p., once a week), a hepatotoxin,
      significantly inhibited the induction of GST-P positive foci, while 4,4'
      diaminodiphenylmethane (DDPM, 0.1% in diet), a bile duct proliferator which is
      itself a hepatocarcinogen, possessed enhancing activity. DDPM, also a goitrogen,
      clearly inhibited the development of follicular cell tumors in the thyroid.
      Uracil (3.0% in diet), which is an inducer of papillomatosis in the urinary
      bladder, did not exert any enhancing potential on bladder carcinogenesis.
      Bleomycin (2 mg/kg b.w., i.p., twice a week), which is an alveolar epithelium
      injuring agent, also did not modify the induction of alveolar epithelium
      proliferative lesions. These results indicate that prior organ injury by toxic
      agents does not always act to enhance sensitivity to carcinogenesis.

PMID- 7505958
TI  - [Return to estrus following first insemination in sow herds (incidence and
      association with reproductivity and various blood parameters)].
AB  - As no systematic study has been done to get an accurate estimate of the incidence
      of return to oestrus after first insemination in sows in the Netherlands, the
      objectives of this investigation were: 1) to obtain an estimate of the incidence
      of return to oestrus after insemination at the herd level; 2) to investigate the
      association between incidence of return to oestrus after first insemination and
      reproduction characteristics to get an impression of the economic importance.
      These objectives were investigated using the reproduction results of 240 swine
      breeding herds in The Southern Netherlands in 1987, using their CBK plus
      computerized herd management records. The average incidence of return to oestrus
      after first insemination on a herd level was 16.9 per 100 first inseminations. An
      increase of incidence with 10 returns per 100 first inseminations, corrected for
      confounders in a multiple linear regression model, was associated with a decrease
      of approximately 0.3 liveborn piglets/sow/year. Thereupon individual sows were
      followed in 1988 and 1989 prospectively in 37 sow herds from weaning to
      insemination, returning to oestrus or not after first insemination to farrowing.
      The investigation focused in particular on the relationship between returning to
      oestrus after first insemination and incident infection with porcine parvovirus
      (PPV) and Leptospira interrogans serovar bratislava (L. bratislava). During a
      number of consecutive farm visits sows were blood sampled at weaning and again a
      blood sample was taken 6 weeks later. The final dataset that was analysed
      consisted of 161 animals that did not return to oestrus after first insemination
      and 158 animals that returned to oestrus after first insemination.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7505959
TI  - Preparation of conjugates of progesterone with bovine serum albumin in the
      reversed micellar medium.
AB  - Progesterone-BSA (bovine serum albumin) conjugates which contain up to 47 steroid
      molecules linked to a BSA molecule have been prepared by the activated ester
      method, the conjugation step being carried out in reversed micellar solutions of
      sodium di(2-ethylhexyl) sulphosuccinate (AOT) in octane. The number of
      incorporated steroid molecules increases on passing to increased water/AOT ratios
      at the given activated steroid/BSA ratio. The results show that the reversed
      micellar medium would be useful for preparation of conjugates of hydrophobic
      steroids with proteins in respect to simplicity and ease in obtaining conjugates
      with high steroid/protein ratios.

PMID- 7505957
TI  - [Protein S deficiency, acute phase reaction and thrombosis].
AB  - Protein S deficiency increases risk of thrombosis. At present, we have
      information on 63 Norwegian individuals with hereditary protein S deficiency
      belonging to 25 different families. 42 of the individuals have experienced at
      least one thromboembolic episode, and seven a cerebral infarction before the age
      of 70 years. The amount of free protein S in plasma is dependent on variation of
      the acute phase protein C4b-binding protein (C4bBP). Acute phase response with
      increased C4bBP induces free protein S deficiency, and increases risk of
      thrombosis. In patients with protein S deficiency, warfarin may reduce free
      protein S to critically low levels, and thus explain why, in some patients,
      recurrent thrombosis occurs during warfarin treatment. In this situation,
      warfarin should be replaced by heparin.

PMID- 7505960
TI  - Validation of use of the Nageotte hemocytometer to count low levels of white
      cells in white cell-reduced platelet components.
AB  - BACKGROUND: Determination of the white cell (WBC) count in WBC-reduced platelet
      components requires methods that have a detection limit in the range of
      approximately 5.0 x 10(2) to 5.0 x 10(4) per mL. STUDY DESIGN AND METHODS: With a
      50-microL Nageotte hemocytometer and bright-field microscopy (200x
      magnification), studies were conducted to develop and validate a method that
      could be used routinely with filtered and apheresis-harvested platelets. A 1-in-5
      dilution of sample with a commercially available blood-diluting fluid was used
      because, with a lower (1-in-2) dilution, the observed number of WBCs was
      substantially less than the number expected at relatively high platelet counts (>
      1.9 x 10(9)/mL). RESULTS: The observed and expected WBC counts in WBC-reduced
      platelet samples correlated well at levels between approximately 5 and 1100 WBCs
      per counting area (5.0 x 10(2)-1.1 x 10(5)/mL). At levels of more than 300 to 400
      WBCs per counting area, accurate counts were obtained when 10 of the 40
      rectangles were counted. CONCLUSION: These studies provide data to confirm that
      the 50-microL Nageotte hemocytometer can be used to accurately count low levels
      of WBCs in platelet components.

PMID- 7505961
TI  - Specificity and sensitivity of two second-generation enzyme-linked immunosorbent
      assays for antibodies to hepatitis C virus in blood donor screening.

PMID- 7505962
TI  - Grounding the flannelgraph.

PMID- 7505964
TI  - [Treatment of prostatic hyperplasia in the 1990's].

PMID- 7505963
TI  - [Systemic-pulmonary anastomoses in Tetralogy of Fallot].

PMID- 7505966
TI  - [Finasteride. A new 5 alpha reductase inhibitor registered for treatment of
      benign prostatic hypertrophy with the purpose of avoiding or postponing surgery].

PMID- 7505965
TI  - [Pharmacological treatment of benign prostatic hyperplasia].
AB  - Over the last five to ten years, new treatment modalities have appeared at an
      increasing pace. The emerging pharmacological treatment modalities have all been
      used on a large scale. The exact indications and limitations of these methods
      have not yet been definitely established. Careful analysis of the symptomatology
      is crucial in counseling the patient. The Danish Prostatic Symptom Score model
      (DAN-PSS) is proposed. However, treatment benefits should exceed harm and there
      must be a reasonable cost-effectiveness. Pharmacological agents that reduce
      prostatic size and/or the tone in the prostate are effective in treatment of
      benign prostatic hyperplasia. Selective alpha-1 blockers seem to be useful in
      patients with uncomplicated benign prostatic hyperplasia and mild to moderate
      symptoms. The side effects of hormone therapy are prohibitive for use in patients
      with a benign disease. Data currently available indicate a yet to be defined role
      for 5-alpha-reductase inhibitors.

PMID- 7505967
TI  - Biomolecular and clinical characteristics of PSA and other candidate prostate
      tumor markers.
AB  - Three new potential biomarkers--PAC, PMA, and the 7E11-C5 glycoprotein--have been
      identified. All three have unique features that could augment current diagnostic
      and therapeutic modalities. Some of the important characteristics of these
      potential markers are summarized in Table 1. Further studies will be required to
      determine if any of them will provide clinical information beyond that provided
      by PSA and if they will have a significant impact on the management of patients
      with prostate cancer. The MAb 7E11-C5 (CYT-356), now in clinical trials, promises
      to offer new strategies for radioimmunodetection and radioimmunotherapy of
      prostate cancer.

PMID- 7505968
TI  - Issues in the assessment of PSA immunoassays.
AB  - The physician and laboratorian have several proven PSA assays from which to
      choose, and several more are likely to achieve FDA approval soon. Furthermore, an
      assay that is FDA approved offers considerable reassurance that the many aspects
      of assay design and manufacturing processes meet an acceptable standard. This
      will become even more critical as assays report values in the ultrasensitive
      range. We have attempted to review here some of the most important issues related
      to PSA assay performance and standardization. Standardization particularly is a
      complex problem for which solutions are just now appearing. Yet efforts must
      continue to minimize controversies, because many more assays will be forthcoming
      and because newer applications of PSA determinations will place more pressure on
      proper assay evaluations. For example, measurement of free PSA, PSA-ACT
      complexes, and the ratio of one to the other are intriguing possibilities for
      added clinical benefit. Also, ultrasensitive PSA assays add a new dimension to
      the detection of residual disease and may provide unique opportunities for the
      implementation of new therapies and their timely evaluation. In our opinion, the
      impact of PSA on the management of prostate cancer is still growing, and the
      opportunities for better and new assays are still great.

PMID- 7505969
TI  - PSA in benign prostatic hyperplasia and prostatic intraepithelial neoplasia.
AB  - Prostate specific antigen has become an important adjunct to the digital rectal
      examination in screening for prostate cancer. The clinician should be familiar
      with interpretation of this test. Many men with BPH have elevated serum PSA
      concentrations; however, the majority of these men will have other pathologic
      processes such as occult cancer, PIN, or acute inflammation that may account for
      the elevations in serum PSA. Certainly, serial increases in serum PSA should
      increase concern that occult carcinoma is present. Patients with PIN may also
      have elevated PSA concentrations. When PIN is associated with elevated PSA, a
      high incidence of invasive carcinoma is noted on subsequent biopsy. Further
      investigation into the associations will further refine the clinical utility of
      this powerful tumor marker.

PMID- 7505971
TI  - PSA as a screening test for prostate cancer.
AB  - With an expected rise in the incidence of prostate cancer, the major challenge of
      the 1990s is to establish standards and procedures for the screening and early
      detection of prostate cancer so that mortality is reduced. Prostate-specific
      antigen (PSA) lacks sufficient sensitivity and specificity to be used alone as a
      screening test for prostate cancer. However, in conjunction with the digital
      rectal examination and transrectal ultrasound, PSA can greatly improve detection
      rates.

PMID- 7505970
TI  - Effect of finasteride on serum PSA concentration in men with benign prostatic
      hyperplasia. Results from the North American phase III clinical trial.
AB  - Finasteride, a 5-alpha reductase inhibitor recently introduced for the treatment
      of symptomatic benign prostatic hyperplasia, reduces prostate size and decreases
      serum PSA concentration. To interpret PSA in men treated with finasteride, it is
      necessary to take the reduction into account. This article describes the effect
      of finasteride on the serum PSA concentration in the North American Phase III
      clinical trial and discusses implications of these findings for the
      interpretation of serum PSA in men treated with finasteride.

PMID- 7505972
TI  - Using PSA to screen for prostate cancer. The Washington University experience.
AB  - The evidence is mounting that PSA-based screening for prostate cancer is rational
      and effective at detecting a high proportion of cancer that is both clinically
      significant and curable by radical prostatectomy. However, more information is
      necessary to define the optimal ages at which screening should be performed and
      to determine the appropriate role of repetitive PSA measurement, PSA density, and
      PSA slope in serial screening. Formal demonstration of a significant screening
      induced reduction of cancer-specific morbidity and mortality is necessary to
      unambiguously justify screening for prostate cancer. A randomized trial
      evaluating prostate cancer screening will soon be started under the auspices of
      the National Cancer Institute. Additionally, refinements in serum PSA testing
      that consider the variable binding of PSA derived from benign and malignant
      prostatic tissues to serum proteins may further enhance the performance of PSA
      testing in the screening setting. For these reasons, PSA-based screening for
      prostate cancer seems destined to remain an important strategy for minimizing the
      health consequences of this disease.

PMID- 7505973
TI  - PSA density (PSAD). Role in patient evaluation and management.
AB  - Prostate Specific Antigen (PSA) is the most accurate serum marker for cancer of
      the prostate. However, sensitivity and specificity are suboptimal, especially at
      the intermediate levels between 4.1 and 10.0 ng/ml (monoclonal). For intermediate
      PSA levels, prostate specific antigen density (PSAD) provides unique information
      regarding the need for biopsy and the likelihood of prostate cancer. This article
      summarizes the utility of PSAD in diagnosing and treating prostate cancer.

PMID- 7505974
TI  - PSA velocity for the diagnosis of early prostate cancer. A new concept.
AB  - An evaluation of longitudinal changes in PSA in men with and without prostate
      disease revealed that with age, the development of prostate disease is the most
      important factor influencing changes in PSA. Furthermore, the PSA changes with
      age are significantly different in men with and without prostate disease. The PSA
      velocity is greater in men with prostate cancer than in men with BPH and greater
      in men with prostate cancer and BPH than in men without any prostate disease.
      Thus, evaluation of PSA changes may help distinguish between men with prostate
      cancer and those without the disease. This idea will need to be confirmed
      prospectively. Finally, estimation of PSA doubling time from changes in PSA
      suggests that changes reflect prostatic growth. Therefore, PSA velocity could be
      of benefit in identifying men with prostate cancer that is destined to progress.

PMID- 7505975
TI  - Influence of patient age on the serum PSA concentration. An important clinical
      observation.
AB  - Although PSA is a most valuable tool for the practicing physician, it lacks
      sufficient sensitivity and specificity for detecting early prostate cancer to be
      the perfect tumor marker. The parameters PSAD and PSA velocity are useful
      attempts to make PSA a better tumor marker, but they likewise are not always
      reliable on an individual basis. There is now evidence from several
      investigations that the serum PSA concentration in healthy men without clinical
      evidence of prostate cancer increases with advancing age. This is primarily
      attributable to the concomitant increase in prostate size over the same time
      period. As a result, age-specific reference ranges have been determined and have
      the potential to make PSA a more sensitive tumor marker for men less than 60
      years of age and a more specific tumor marker for men beyond 60 years of age. If
      one utilizes the age-specific reference ranges for serum PSA, it appears that
      PSAD can be eliminated as a parameter in the diagnostic evaluation of patients
      suspected of having prostate cancer. Thus, a new algorithm utilizing age-specific
      reference ranges has been developed.

PMID- 7505976
TI  - Significance of different molecular forms of serum PSA. The free, noncomplexed
      form of PSA versus that complexed to alpha 1-antichymotrypsin.
AB  - Prostate specific antigen is an abundant prostate-derived serine protease in the
      seminal fluid. Low concentrations of the protein are normally released into
      blood, but above normal concentrations are frequently detected in prostate
      disease. The PSA-ACT complex is the predominant molecular form of serum PSA (up
      to approximately 95%) although complex formation is slow between the purified
      proteins in vitro. A free, noncomplexed form of PSA constitutes a minor fraction
      of the serum PSA, although serum ACT occurs in large molar excess. The free,
      noncomplexed form of serum PSA is reported to constitute a significantly smaller
      proportion of the PSA in untreated prostate cancer than in BPH. The molecular
      basis for this finding is unclear, but measurements of the proportion of the free
      form of serum PSA or the proportion of serum PSA-ACT may facilitate
      discrimination between prostate cancer and BPH.

PMID- 7505977
TI  - PSA-detected (clinical stage T1c or B0) prostate cancer. Pathologically
      significant tumors.
AB  - With the rapidly spreading enthusiasm for early detection of prostate cancer and
      the increasing use of serum PSA to evaluate the gland, more cancers that are not
      palpable on digital rectal examination are being identified. These tumors have
      pathologic characteristics that are very similar to those of clinically
      localized, palpable prostate cancers identified on digital rectal examination.
      Thus, the tumors detected on the basis of an elevated serum PSA value should not
      be disregarded as insignificant. In fact, these tumors should be given the same
      therapeutic consideration as the clinically localized, palpable cancers. In the
      TNM staging system, "PSA-detected" cancers can be classified as stage T1c, and in
      the Whitmore-Jewett staging system, they can be referred to as stage B0. Long
      term follow-up of these prostate cancers will be necessary to establish the
      prognosis.

PMID- 7505978
TI  - PSA and staging of localized prostate cancer.
AB  - Numerous studies have demonstrated a direct relationship between serum PSA and
      tumor volume. However, because of a substantial overlap between serum PSA
      concentrations and advancing clinical and pathologic stages, serum PSA has been
      found to be unreliable for predicting the final pathologic stage in an individual
      patient. Nevertheless, by combining various other preoperative measures such as
      clinical stage, biopsy grade, or both, several investigators have determined that
      the predictive power of serum PSA for pathologic stage can be significantly
      enhanced. Explanations for the failure of the serum PSA concentration alone to be
      useful in predicting final pathologic stage include the unpredictable
      contribution from the BPH component of the gland and the decreasing production of
      serum PSA by higher-grade lesions with increasing tumor volume.

PMID- 7505979
TI  - Using PSA to eliminate the staging radionuclide bone scan. Significant economic
      implications.
AB  - The findings of these two large-scale clinical studies indicate that serum PSA is
      an accurate and reliable predictor of the bone scan findings for 40% of the
      patients presenting with newly diagnosed, untreated prostate cancer. For these
      patients with no skeletal symptoms and a serum PSA value of 10 ng/mL or less by
      either the Tandem-R or the IMx assay, a staging radionuclide bone scan is not
      necessary, as it provides no additional useful information over what is learned
      from the serum PSA value. If these bone scans were eliminated for these selected
      patients, approximately $38 million could be saved annually in the United States.
      As the incidence of newly diagnosed prostate cancer continues to increase, so
      will the economic savings associated with using the serum PSA concentration to
      predict the bone scan findings in appropriate patients.

PMID- 7505980
TI  - Serum PSA after anatomic radical prostatectomy. The Johns Hopkins experience
      after 10 years.
AB  - 1. With an average follow-up of 53 months (range 12-120 months), 19.4% (185/955)
      of men have had a cancer recurrence after radical prostatectomy for clinically
      localized prostate cancer. A detectable serum PSA was the only evidence of
      recurrence in 11.2%, whereas 2.2% have had a recurrence locally and 6% with
      distant metastases. 2. The actuarial status at 10 years was 70% for undetectable
      serum PSA; 23% for isolated serum PSA elevation only; 7% for distant metastases;
      and 4% for local recurrence. 3. In our study, no patient demonstrated disease
      progression (local or distant) without detectable serum PSA. 4. The actuarial
      likelihood of an elevated serum PSA increased with increasing clinical stage,
      Gleason score, preoperative serum PSA concentration, and pathologic stage. 5. The
      actuarial recurrence rate for tumors with a Gleason score of 7 was not
      statistically different from the recurrence rate for lesions of Gleason score 8
      10. 6. There exist marked differences in actuarial recurrence-free probabilities
      for men with tumors of low Gleason score (< 7) compared with those with tumors of
      high Gleason score (> or = 7) when there is pathologically established capsular
      penetration. 7. Patients with preoperative serum PSA concentrations greater than
      10.0 ng/mL are at a statistically increased risk of recurrence. 8. Men who have
      detectable serum PSA within the first year after surgery are at a significantly
      higher risk of disease progression than those men who have measurable serum PSA
      in postoperative years two and three. 9. Men with an isolated elevation of serum
      PSA after radical prostatectomy have a 25% likelihood of harboring an occult
      local recurrence. However, radiation therapy produces a sustained suppression of
      PSA to undetectable levels for 2 years or more in only 10% of men. This suggests
      that radiation therapy is not effective in sterilizing occult local residual
      tumor in many men. 10. Valuable information concerning disease recurrence and
      progression can be obtained through early postoperative measurement of serum PSA.
      This article demonstrates the long-term value of serum PSA as a measure of
      progression after anatomic radical prostatectomy.

PMID- 7505982
TI  - Serum PSA as a tumor marker for patients undergoing definitive radiation therapy.
AB  - This article summarizes the clinical utility of PSA both as pretreatment
      prognostic factor and as an invaluable post-treatment marker. Some pathobiologic
      correlations between serum PSA kinetics and putative tumor cell kinetic
      mechanisms are discussed.

PMID- 7505981
TI  - PSA after definitive radiotherapy for clinically localized prostate cancer.
AB  - A rising PSA level for clinically localized prostate cancer after definitive
      radiotherapy is an ominous finding that correlates with positive postirradiation
      biopsy and traditional clinical progression. The study detailed in this article
      found that the proportion of patients treated with radiotherapy who achieved
      stable PSA levels and were clinically free of disease was disappointingly low.

PMID- 7505983
TI  - Serum PSA after antiandrogen therapy.
AB  - Patients who present with advanced prostate cancer and who are treated with
      primary endocrine therapy have a significantly longer time to progression and a
      clear survival advantage if their serum PSA concentration normalizes. The
      prognostic significance of normalization of PSA is independent of other
      prognostic measures. Normalization of serum PSA at month 3 is the earliest and
      most highly correlated predictor of response. Most patients (80%-85%) who have
      disease progression while on hormonal therapy will show a rising PSA 6 to 12
      months before other clinical findings become abnormal. A rising PSA in the
      hormonally treated patient, even if the values are within the "normal" range,
      signals impending clinical progression. These patients should be considered for
      second-line hormonal therapies or alternative salvage protocols, as a
      theoretically favorable window of opportunity may exist when the PSA begins to
      rise. Patients treated with second-line therapies should also undergo serial PSA
      measurements; those responding with an 80% to 90% decrease in serum PSA are
      statistically more likely to enjoy a prolonged response.

PMID- 7505984
TI  - PSA and PAP as immunohistochemical markers in prostate cancer.
AB  - This article describes the immunoreactivity of PSA and PAP in non-neoplastic and
      neoplastic prostate tissue. Listed are examples of cross reactivity of PSA and
      PAP in non-neoplastic and neoplastic tissue from other organs. The use of PSA and
      PAP to identify tumors of prostatic origin in different sites is also described.
      Finally, the diagnostic uses of immunohistochemistry for PSA and PAP in prostate
      biopsies and for prognostication are discussed.

PMID- 7505985
TI  - Future directions in tumor marker technology for prostate cancer.
AB  - This article assesses the likely role of PSA in the future management of patients
      with carcinoma of the prostate, taking into consideration new methods for
      measurement and assessment. In addition, novel tumor markers are discussed that
      may complement, or even perhaps replace, PSA.

PMID- 7505986
TI  - Inhibition of Mycoplasma bovis cytadherence by a monoclonal antibody and various
      carbohydrate substances.
AB  - The attachment of Mycoplasma bovis to permanent embryonic bovine lung (EBL) cells
      was studied in order to identify factors participating in the adhesion process. A
      monoclonal antibody directed against a 26 kDa protein of M. bovis was shown to
      reduce cytadherence of strains 120 and 454 by 46% and 70%, respectively. In
      uninhibited assays, strain 120 which exhibits an intense 26 kDa band in
      electrophoretic protein patterns adhered more strongly to EBL cell monolayers
      than strain 454 whose corresponding band is considerably weaker. The findings
      indicate involvement of the 26 kDa protein in M. bovis adherence. In further
      inhibition experiments, the ability of N-acetyl-neuraminlactose, glycophorin and
      dextran sulfate to significantly reduce adherence could be demonstrated. This
      suggests participation of sialic acid residues and probably also sulfatide groups
      as binding receptors. The data point to a complex adhesion mechanism with
      similarities to M. pneumoniae.

PMID- 7505987
TI  - [The neurohumoral status in depression].
AB  - In 66 patients with endogenous depression (34 males and 32 females) the
      concentrations of biogene amine metabolites (vanilmandelic acid (VMA), 5
      hydroxyindole acetic acid (5-HIIA), adrenaline and noradrenaline) were examined
      in 24-hrs urine and hormone in the serum: iodothyronine (T-3), thyroxine (T-4),
      thyroglobulin (Tg), thyroid-stimulating hormone (TSH), adrenocorticotropic
      hormone (ACTH), cortisol, prolactin and growth hormones. The examination was
      performed prior to the initiation of antidepressant therapy and 30 days after its
      application. The biogene amine metabolites were in reference values before
      initiation of the therapy, although values of 5-HIIA in women and were closer to
      the lower limit. Thirty days after the initiation of the antidepressant therapy
      the statistically significant difference was found at the level of p < 0.05 for
      adrenalin in men and for VMA and 5-HIIA in women. The hormone values before
      initiation of the therapy showed increased values of growth hormone, cortisol in
      men and of thyroglobulin, growth hormone and cortisol in women. At the end of the
      antidepressant therapy the statistically significant difference was found at the
      level of p < 0.05 for thyroglobulin and TSH in men and for thyroglobulin, growth
      hormone and cortisol in women. By comparing the results obtained before and after
      the antidepressant therapy, the statistically significant difference was found at
      the level of p < 0.05 for Tg in men and for Tg, T-3, prolactin and growth hormone
      compared to the women. It has been concluded that in patients with endogenous
      depression the important role in pathogenesis of the disease have some
      neurobiogenic disorders.

PMID- 7505988
TI  - [Interferon therapy in Hodgkin's disease].
AB  - Though there are only limited reports interferon (IFN) seems an interesting
      substance for patients with Morbus Hodgkin. Overall response rate is about 20% in
      heavily pretreated patients. Even patients after bone marrow transplantation
      showed response. This suggests to treat patients in a earlier phase of their
      disease. Combination of interferon with radiotherapy or chemotherapy might be
      promising. Prospective studies investigate the value of IFN for maintenance. It
      seems that patients treated with IFN have less relapses and better
      immunorestorations. Whether IFN can prevent secondary malignancies is also topic
      of these investigations. As IFN has complex side effects it should be applied
      only in controlled studies.

PMID- 7505989
TI  - [Interferon therapy of the lung and locoregional therapy in pulmology].
AB  - The constant increase of lung cancer incidence is confronted with the relatively
      low efficacy of drug therapy in patients with advanced stages of this disease.
      According to results of phase II studies interferon-alpha (IFN-alpha) monotherapy
      used as palliative measure is ineffective in all histological types of lung
      cancer. However, in certain therapy settings IFN-alpha has some efficacy. In
      small cell lung cancer IFN-alpha therapy, when given as maintenance following
      chemo- and/or radiation therapy-induced remissions, has shown some clinical
      benefit as documented by a prolongation of remission-free intervals. In patients
      with advanced non-small cell lung cancer and especially of the squamous cell type
      the combination of IFN-alpha with cisplatinum achieved remissions in about 45%.
      The efficacy of locoregional administration, i.e. intrapleural, in patients with
      malignant effusions is currently under investigation.

PMID- 7505990
TI  - [New aspects of interferon therapy in malignant diseases].
AB  - Recombinant Interferon-alpha (IFN-alpha) preparations are now used for more than
      10 years for treatment of hematological, oncological and viral diseases. New
      insights into the influence of IFN on the metabolism of cytostatic agents, i.e.
      biochemical modulation, opens a new spectrum of combination therapies. The
      efficacy of locoregional administration (intraperitoneal, -pleural, perilesional,
      intravesical) is probably based on a direct effect of this agent on both tumor
      and effector cells. Inhibition of angiogenesis is one of the proposed mechanisms
      responsible for the efficacy of IFN in life-threatening hemangiomas and might
      have also some potency in the adjuvant therapy of cancer. Presently IFN is used
      in combination with biological response modifiers, cytokines and especially a
      synergistic therapeutic effect is documented with retinoids. The possibility of
      direct stimulating effects of IFN on the immune system should be considered
      particularly in future studies.

PMID- 7505993
TI  - [Personality markers in patients with Sudeck's disease. A psychoanalytic study].
AB  - We examined 22 patients suffering from reflex sympathetic dystrophy with
      psychoanalytic interviews. In all 22 patients we found a common psychological
      structure corresponding to Balint's basic fault (Balint, 1970). For people with
      this structure the accident that preceded the reflex sympathetic dystrophy and
      the following pain, immobilisation and need to help are promoting the patient's
      regression in a specific way ending in the developing of reflex sympathetic
      dystrophy. The dispair of the patients about their reflex sympathetic dystrophy
      expresses unsolved fears of early childhood.

PMID- 7505992
TI  - [Blood screening for Down's syndrome in women under 35 years of age with an age
      independent index].
AB  - The need for alternatives to amniocentesis, beset by 1% abortion rate, has been
      increasingly voiced over the past years and also includes the under 35 age group.
      However, the known age-dependent screening programs such as Alpha program
      according to Wald (1988) and the Dermalog Program according to Norgaard-Pederson
      (1990) only yield a detection rate of 50 or, at best, 70% (Muller, 1992) for this
      age group. We tried to improve this result by index calculation. Compared to the
      tested age-dependent screening programs the Ulm Index achieves a 25 to 40% higher
      detection rate (85%). For pregnant women beyond 35 years the detection rate of
      Down's syndrome can even be raised to 95-100% by a combination of the Alpha or
      Dermalog program with the Ulm Index, without entailling an increase in the rate
      of false-positive results.

PMID- 7505991
TI  - Palliation of malignant dysphagia using the Nd:YAG laser.
AB  - A group of 141 patients with biopsy-proved malignant dysphagia, treated with
      neodymium YAG laser between April 1985 and November 1988, have been prospectively
      evaluated. Patients treated since November 1988 have not been included to allow
      minimum follow-up of 18 months. The success of treatment has been assessed in
      terms of survival, relief of dysphagia, complications, and length of inpatient
      stay. One- and two-year survival rates were 12.6% and 3.5%, respectively (mean
      survival 24.7 weeks). Ninety-two percent of patients were returned to a semisolid
      diet or better. In 4% recanalization was impossible, and 4% swallowed only
      liquids despite an adequate channel. Tumor histology, site of tumor, and length
      of previous treatment had no significant influence on outcome. The presence of
      metastases significantly influenced survival (p = 0.007). The principal
      complications were perforation (6.4%) and tracheoesophageal fistula (2.8%). Laser
      recanalization provides effective palliation for malignant dysphagia.

PMID- 7505994
TI  - Loss of ICG uptake in the process of rat hepatocarcinogenesis correlates to the
      disappearance of glutathione-S-transferase alpha subunit.
AB  - Reduced indocyanine green (ICG) uptake is one of the functional changes of human
      hepatocellular carcinoma (HCC). To clarify the mechanisms of loss of ICG uptake,
      and determine which subunit of glutathione-S-transferase (GST), alpha or pi,
      plays a role in ICG transport in hepatocytes, an experimental HCC model was
      developed that used nodules induced by 2-acetylamino-fluorene (2-AAF)
      administration. Many of the ICG stained nodules, which consisted of benign and
      borderline lesions, were GST-alpha positive. However, the percentage of GST-alpha
      positive cells tended to decrease according to the disappearance of ICG staining
      in the process of hepatocarcinogenesis. HCCs unstained by ICG were also GST-alpha
      negative. GST-pi, not detected in normal rat hepatocytes, appeared in an earlier
      stage of hepatocarcinogenesis before the disappearance of GST-alpha, and was not
      observed in HCCs. No significant relationship between ICG staining and GST-pi was
      recognized. These results suggest that GST-alpha synthesis is disturbed in the
      process of hepatocarcinogenesis and results in loss of ICG uptake in HCCs, and
      also indicate that GST-pi may be useful for early diagnosis of preneoplastic
      hepatocytes showing no roles in ICG transport.

PMID- 7505995
TI  - IgE-mediated allergic reaction in drug-induced asthma.
AB  - Immunoallergological studies were carried out to clarify the differences between
      24 patients with drug-induced asthma (DIA) and 240 with non-drug-induced asthma
      (non-DIA). The mean values of age, skin reaction to Candida albicans (C.
      albicans), serum IgE levels, specific IgE antibodies to house dust (HD) and C.
      albicans, bronchial sensitivity and leukotriene B4 (LTB4) synthesis from
      peripheral venous blood in patients with DIA were not significantly different
      from those in patients with non-DIA. In contrast, the frequency of positive skin
      reaction to HD and histamine release from peripheral basophils by anti-IgE were
      significantly lower in DIA than in non-DIA. These results agree with the reports
      that DIA was often observed in non-atopic asthma. But, the mean value of serum
      IgE was very high in DIA as well as in non-DIA. This result suggests that IgE
      mediated reaction in DIA is important. Furthermore, the proportion of neutrophils
      in bronchoalveolar lavage fluid (BALF) was significantly lower in DIA than in non
      DIA. Our findings suggest that a decrease of intrapulmonary neutrophils might
      play an important role in the pathophysiology of DIA.

PMID- 7505996
TI  - Chemical mediator and cellular reaction in the bronchoalveolar lavage fluid of
      patients with steroid-dependent intractable asthma (SDIA).
AB  - The effects of long-term glucocorticoid therapy on chemical mediator and cellular
      reaction in the airways were examined in 69 patients with bronchial asthma. The
      histamine release induced by Ca ionophore A23187 from cells in the
      bronchoalveolar lavage (BAL) fluid of atopic asthmatics was significantly lower
      in the subgroup with steroid-dependent intractable asthma (SDIA) than in non-SDIA
      patients (p < 0.05). In contrast, histamine release in nonatopic SDIA patients
      did not differ from nonatopic non-SDIA patients. The release of leukotriene C4
      (LTC4) was significantly lower in atopic patients with SDIA (p < 0.02). However,
      there was no significant difference in LTC4 release between nonatopic patients
      with SDIA and without SDIA. The proportion of BAL lymphocytes was significantly
      lower in atopic patients with SDIA than in those without it (p < 0.05), although
      there was no significant difference between the nonatopic patients with and
      without SDIA. These results show that glucocorticoids affect humoral and cellular
      events in the airways of atopic asthmatics more than in those of nonatopic
      asthmatics.

PMID- 7505997
TI  - Sulfuric acid induces airway hyperresponsiveness to substance P in the guinea
      pig.
AB  - We investigated whether sulfuric acid inhalation would cause hyperresponsiveness
      to substance P. Guinea pigs became dyspneic during a 1 h sulfuric acid exposure,
      but recovered by 24 h when they were challenged with substance P or histamine
      aerosols. Eight minutes after the start of challenge, animals were killed and
      excised lung gas volumes measured. Sulfuric acid slightly increased histamine
      responsiveness compared to controls. However, sulfuric acid caused a much more
      pronounced leftward shift in the dose response to substance P. Coadministration
      of the neutral endopeptidase (NEP) inhibitor, thiorphan, did not reduce sulfuric
      acid-related hyperresponsiveness to substance P. By 72 h, sensitization to
      substance P was absent. Histological evaluation of sulfuric acid-treated lungs
      revealed mild alveolitis at 24 h, but not at 72 h. We conclude that sulfuric acid
      produces a marked sensitization to substance P. Inactivation of NEP does not
      appear to account for this effect.

PMID- 7505998
TI  - Rapamycin inhibits airway leukocyte infiltration and hyperreactivity in guinea
      pigs.
AB  - The effect of rapamycin on cell infiltration to the lung and on bronchial
      hyperreactivity induced by an intravenous injection of sephadex beads to guinea
      pigs was investigated. One day following the injection of sephadex the total cell
      number in bronchoalveolar lavage (BAL) fluid was significantly increased from
      24.77 to 83.45 x 10(6) cells. This was reflected in an increase in eosinophils,
      neutrophils, macrophages and lymphocytes. In addition, there was an increase in
      the reactivity of isolated bronchial strips to histamine. Rapamycin (5 mg/kg),
      administered two hours before the injection of sephadex, reduced the eosinophil,
      neutrophil, lymphocyte and macrophage number by 64%, 55%, 50% and 19%,
      respectively, and also inhibited the increased reactivity of isolated bronchial
      strips to histamine. These results suggest that rapamycin may reduce bronchial
      reactivity by the inhibition of leukocyte migration into the airways.

PMID- 7505999
TI  - A proposed autacoid mechanism controlling mastocyte behaviour.
AB  - Evidence is provided here supporting the existence of a novel autacoid mechanism
      negatively modulating mast cell behaviour in response to noxious stimuli in vivo;
      hence, the denomination "autacoid local inflammation antagonism" (ALIA). In
      particular, as lipid amides of the N-acylethanolamine type have been reported to
      accumulate in tissues in degenerative inflammatory conditions, we examined
      whether these N-acylated lipids could exert regulatory effects on mast cell
      activation in vivo. The results reported show that both long- and short-chain N
      acylethanolamines, when systemically administered, are effective in reducing mast
      cell degranulation induced by local injection of substance P in the ear pinna of
      developing rats. These and other data suggest that the endogenous production of N
      acylethanolamines may constitute a local autocrine/paracrine response for the
      negative feedback control of mast cell responses to various activating signals.
      Such a process may be of physio-pathological relevance in the regulation of
      functional neuro-immune-mast cell interactions.

PMID- 7506000
TI  - A stromelysin assay for the assessment of metalloprotease inhibitors on human
      aggregated proteoglycan.
AB  - Human proteoglycan was aggregated to an immobilized hyaluronan solid phase on a
      96-well ELISA plate. This complex was then degraded by recombinant human
      stromelysin. The remaining proteoglycan fragments were detected using a
      monoclonal antibody probe directed against the chondroitin sulfate (CS) region of
      the core protein. Stromelysin degraded the aggregate in a time and dose dependent
      manner as reflected by the loss of the CS epitope. Assay sensitivity was 0.125
      U/well with total loss of the CS epitope occurring at 4 U/well. o-phenanthroline
      (IC50 = 52 microM) and U24522 (IC50 = 9 microM) inhibited degradation, while
      phosphoramidon did not. Serine and cysteine protease inhibitors had no effect. A
      comparative analysis of this assay with a reference method, substance P assay,
      gave similar inhibitor profiles. The use of aggregated human proteoglycan (native
      conformation) as a substrate, may better reflect how stromelysin inhibitors
      behave in the presence of complex substrates such as cartilage matrix.

PMID- 7506002
TI  - A comparison of chondrocyte proteoglycan metabolism in monolayer and agarose
      cultures.
AB  - Bovine chondrocyte cultures were established in agarose and in monolayers to
      compare the effects of cytokines and drugs on matrix metabolism. The production
      of sulfated glycosaminoglycans (S-GAG) from the medium and cell surface
      compartments were measured by a dimethylmethylene blue assay. In the agarose
      cultures most of the proteoglycan remained in the agar, but was continuously
      released into the medium for more than 50 days. In the monolayers, the cell
      surface compartment became saturated with S-GAG in 5-6 days. Then a time
      dependent decrease of accumulation occurred in the medium after 8-10 days. The
      anabolic effects of insulin-like growth factor (IGF) and a protein kinase C
      activator (PMA) were measured in these cultures. IGF and PMA increased S-GAG
      accumulation in the medium from monolayers but not from agarose cultures. In the
      agarose cultures, S-GAG was released into the medium after these cultures were
      changed to serum-free test conditions. This release overshadowed any increase in
      S-GAG synthesis. The catabolic effect of IL-1 was more evident in the monolayers
      than in the agarose cultures. Agarose cultures maintain the chondrocyte phenotype
      longer than monolayers but for initial drug studies monolayer cultures appear to
      be more appropriate.

PMID- 7506001
TI  - Sensitivity of monoclonal antibody, 5-D-4, for the detection of aggrecan,
      aggrecan fragments, and keratan sulfate.
AB  - Bovine nasal septum aggrecan and selected proteinase-digested products of
      aggrecan were evaluated in an inhibition ELISA using the anti-keratan sulfate
      (KS) monoclonal antibody 5-D-4 (5D4). Undegraded aggrecan was recognized with an
      IC50 of 0.27 microgram/ml. When aggrecan was treated with human stromelysin
      (SLN), human leukocyte elastase (HLE), or papain, the degradation fragments had
      different hydrodynamic sizes. Treatment with SLN produced the largest fragments,
      HLE generated intermediate fragments, and papain the smallest fragments. Whereas
      degradation of aggrecan by SLN had little effect on recognition of proteoglycan
      in the ELISA (IC50-0.5 microgram/ml), degradation by both HLE and papain
      significantly decreased the sensitivity for detection of KS epitope (IC50-700 and
      215 micrograms/ml, respectively). In addition, 5D4 detected single chain costal
      and corneal KS with much less sensitivity (IC50-21 and 469 micrograms/ml,
      respectively) than undegraded aggrecan (IC50-0.27 microgram/ml).

PMID- 7506003
TI  - Nitric oxide: the Jekyll and Hyde of gut inflammation.
AB  - We studied the effects of seven day treatment with the nitric oxide synthase
      (NOS) inhibitor NG-nitro-L-arginine (L-NAME), administered in the drinking water
      (100 micrograms/ml ad lib) of female guinea pigs. The effects of NOS inhibition
      were evaluated in naive animals and in guinea pigs with ileitis induced by
      intraluminal trinitrobenzenesulfonic acid (TNBS). After 7 days, animals were
      anesthetized, a sterile saline lavage injected into an ileal loop and removed
      after 30 min for analysis. In naive guinea pigs, L-NAME caused a marked increase
      in ileal myeloperoxidase activity and conversion of the mucosa from an absorptive
      to a secretory state. TNBS-treated guinea pigs has a similar, marked increase in
      granulocyte infiltration and a mucosal secretory response. However, in contrast
      to naive animals, L-NAME treatment was anti-inflammatory, reverting all responses
      to the basal state. We conclude that intestinal nitric oxide serves an anti
      inflammatory role under basal conditions, whereas in the TNBS model of chronic
      ileitis, nitric oxide is a critical mediator of gut injury.

PMID- 7506004
TI  - Inhibition of interleukin-1 (IL-1) and tumor necrosis factor (TNF) production by
      pyridinyl imidazole compounds is independent of cAMP elevating mechanisms.
AB  - Exposure of human monocytes (HM) to E. coli lipopolysaccharide (LPS) results in
      measurable production of both IL-1 beta and TNF alpha in culture supernatants. It
      has previously been reported that the elevation of cAMP levels in HM selectively
      suppresses the LPS-induced TNF alpha but not IL-1 beta production. In this study
      we investigated whether the novel anti-inflammatory drug, SK&F 86002 [5-4(
      pyridyl)-6(4-fluorophenyl)-2,3-dihydroimidazole(2,1-b)thi azol] and related
      analogs of the pyridinyl imidazole class, inhibit IL-1 and TNF production via a
      cAMP-dependent mechanism. These compounds, when added together with LPS result in
      inhibition of IL-1 and TNF production with equal-rank-order potency. Although the
      pyridinyl imidazole compounds were found to be generally weak phosphodiesterase
      inhibitors, they did not affect cAMP levels in HM, alone or in the presence of
      LPS. In contrast, PGE2, which significantly elevated intracellular cAMP levels,
      inhibited TNF but not IL-1 production at the transcriptional level. Taken
      together, these results suggest that the pyridinyl imidazoles inhibit the
      production of IL-1 beta and TNF alpha through pathways independent of cAMP
      elevating mechanisms.

PMID- 7506005
TI  - Twin pregnancies in the second trimester in women in an alpha-fetoprotein
      screening program: sonographic evaluation and outcome.
AB  - OBJECTIVE: We correlated sonographic findings with fetal outcomes in women with
      unsuspected twin pregnancies who had sonography in the second trimester as part
      of a screening program for maternal serum alpha-fetoprotein (MSAFP) level and
      history of neural tube defect. MATERIALS AND METHODS: The study group consisted
      of 97 women with twin pregnancies who participated in a screening program for
      MSAFP level and history of neural tube defect. Seventy-three had normal MSAFP
      levels, 21 had elevated MSAFP levels, and two had low MSAFP levels. One patient
      had a family history of anencephaly. All 97 patients had sonography during their
      second trimester of pregnancy. Sonographic findings were reviewed retrospectively
      for information on gestational age, fetal anomalies, sex of the fetus, location
      of the placenta, presence and thickness of a dividing membrane, and
      interpretation of amnionicity and chorionicity. Information on fetal outcome
      included gestational age at delivery, survival, birth weight, sex, congenital
      anomalies, obstetric complications, amnionicity, chorionicity, and placental
      abnormalities. RESULTS: Amnionicity and chorionicity were correctly detected on
      sonograms in 44 (90%) of 49 diamniotic-dichorionic gestations, 23 (72%) of 32
      diamniotic-monochorionic gestations, and two (50%) of four monoamniotic
      monochorionic gestations. Fetal anomalies were present at delivery in five
      neonates and had been correctly detected at sonography in one (hemivertebra); one
      fetus with duodenal atresia had abnormal sonographic findings in the third
      trimester. Missed anomalies included absent forearm, cleft lip and palate, and
      imperforate anus. Sex of the fetuses was correctly predicted on the basis of
      sonographic findings in 40 of 43 pairs. Nine twin pairs had possible twin-twin
      transfusion syndrome suspected sonographically on the basis of abnormal fluid
      volumes, discrepant growth measurements, and abnormal findings on Doppler
      studies. Outcomes included two confirmed cases of the syndrome (two survivors,
      two deaths) and three probable cases (six deaths); four pregnancies resulted in
      eight survivors who were delivered after 34.4 weeks' gestation and had birth
      weights in the 25th percentile or higher. Survival rates for diamniotic
      dichorionic, diamniotic-monochorionic, and monoamniotic-monochorionic gestations
      were 90%, 91%, and 50%, respectively. Fetuses in women with MSAFP levels greater
      than 4.5 multiples of the median and with monochorionic placentation had lower
      survival rates than fetuses in women with normal MSAFP levels and monochorionic
      placentation (67% vs 96%). Half the fetuses delivered after 20 weeks' gestation
      had birth-weight discordance of less than 10%. Premature deliveries occurred in
      56% of pregnancies. CONCLUSION: The results suggest that (1) sonography is useful
      in predicting placentation, (2) placentation may be helpful in predicting fetal
      outcome, (3) increased MSAFP levels correlate with increased perinatal mortality
      in diamniotic-monochorionic pregnancies, and (4) caution should be taken in
      diagnosing and determining prognosis for suspected twin-twin transfusion syndrome
      in the second trimester.

PMID- 7506006
TI  - Twin pregnancies in women in an alpha-fetoprotein screening program.

PMID- 7506007
TI  - Correlates of ventricular ectopic activity in isolated systolic hypertension.
      SHEP Cooperative Research Group.
AB  - Ventricular ectopic activity was recorded at baseline in 5.6% of the 12-lead
      electrocardiograms and 8.2% of the 2-minute rhythm strips of 4674 subjects with
      isolated systolic hypertension (systolic blood pressure 160 to 219 mm Hg,
      diastolic blood pressure < 90 mm Hg) participating in the Systolic Hypertension
      in the Elderly Program (SHEP). In this study 1.3% had 6 to 10 ventricular
      premature beats (VPB), and 0.7% had > 10 VPB on the 2-minute rhythm strip.
      Correlates of VPB presence on the 12-lead ECG were older-age male sex, presence
      of Q/QS pattern and higher heart rate. Participants with serum potassium < 3.5
      mmol/L had a higher prevalence of VPB. Similarly, the number of VPB on the 2
      minute rhythm strip was associated with male sex, increasing age, with lower
      serum potassium, history of palpitations, and presence of Q/QS patterns.

PMID- 7506009
TI  - Selective use of Sandostatin in vascularized pancreas transplantation.
AB  - Despite improving results, the management of exocrine complications after
      pancreas transplantation remains problematic. During a 30-month period, we
      performed 65 pancreas transplants with bladder drainage. A total of 23 patients
      (35%) were managed with a long-acting somatostatin analogue (Sandostatin) for
      persistent hyperamylasemia or allograft pancreatitis. Sandostatin was begun at a
      mean of 29 days after transplant with a mean duration of therapy of 13 days.
      Sandostatin therapy was associated with significant reductions in the serum,
      urine, and peritoneal fluid amylase levels (p < 0.05). Sandostatin also caused a
      decrease in cyclosporine levels during oral cyclosporine use. In patients
      receiving Sandostatin, pancreas allograft survival was 83%. We conclude that
      pancreatitis remains a major cause of morbidity after pancreas transplantation.
      The selective use of Sandostatin can result in excellent graft salvage with low
      morbidity. Sandostatin appears to be safe and effective in reducing the exocrine
      output of the denervated pancreas allograft but also reduces cyclosporine levels.

PMID- 7506010
TI  - Palliative operations for pancreatic cancer in the hospitals of the U.S.
      Department of Veterans Affairs from 1987 to 1991.
AB  - A total of 1,180 patients underwent palliative surgery for pancreatic cancer in
      the 158 hospitals of the U.S. Department of Veterans Affairs from 1987 to 1991.
      Using computerized data files, we analyzed these procedures according to type of
      procedure (gastric bypass only [GO], biliary bypass only [BO], or combined
      biliary and gastric bypass [BG]), survival, reoperation and complication rates,
      patient age, and operative (30-day) mortality. Survival after GO (208 days) was
      significantly shorter than after BO or BG (279 days and 259 days, respectively; p
      < or = 0.05 by analysis of variance). The reoperation rate after BO (12%) was
      higher than after BG (5%; p < or = 0.001 by chi 2 analysis) and was due to the
      higher incidence of reoperative gastric bypass in the BO group. Complication
      rates were similar after all bypass types. Reoperations had a 25% 30-day
      mortality. The 32 gastric bypasses performed after an initial BO were done at a
      mean of 193 days after the original BO bypass, whereas other reoperations were
      undertaken at a mean of 73 days after the first operation. This first national
      study of palliative operations for pancreatic cancer supports combined
      biliary/gastric bypass as the initial procedure, thus minimizing reoperations and
      their attendant morbidity.

PMID- 7506008
TI  - Role of dietary magnesium deficiency in the pressor and arrhythmogenic response
      to epinephrine in the intact dog.
AB  - The effect of dietary magnesium deficiency on the pressor and arrhythmogenic
      responses to epinephrine was investigated in 19 dogs maintained either on a
      normal diet (11 dogs) or a diet deficient in magnesium (8 dogs). Magnesium
      deficient dogs had significantly lower serum magnesium levels than the control
      dogs on a normal diet. Magnesium-deficient dogs showed an increased pressor
      sensitivity to epinephrine as determined by the dose of epinephrine required to
      cause a maximal pressor response (3.4 micrograms/kg/min compared to 13.4
      micrograms/kg/min, p < 0.05). Magnesium-deficient dogs also had a significantly
      lower threshold dose for ventricular premature beats (0.8 microgram/kg/min
      compared to 2.7 micrograms/kg/min, p < 0.05). Acute administration of magnesium
      sulfate restored pressor sensitivity and ventricular premature beat threshold to
      normal levels in the magnesium-deficient dogs. Threshold dose for ventricular
      tachycardia beat was similar in both normal and magnesium-deficient dogs, and
      threshold was raised significantly in both groups by acute administration of
      magnesium.

PMID- 7506011
TI  - Laparoscopic cholecystectomy in biliary pancreatitis.
AB  - Laparoscopic cholecystectomy has emerged as the treatment of choice for
      uncomplicated cholelithiasis. Despite early concerns, many surgeons have applied
      this new technique to more complicated biliary tract disease states, including
      biliary pancreatitis. To evaluate the safety of laparoscopic cholecystectomy in
      this setting, we retrospectively reviewed 29 patients with clinical and
      laboratory evidence of biliary pancreatitis who underwent this procedure between
      March 1990 and December 1992. The severity of pancreatitis was determined by
      Ranson's criteria. Two patients had a Ranson's score of 6, one of 5, one of 4,
      five scored 3, nine scored 2, nine also scored 1, and two patients scored 0. The
      mean serum amylase level on admission was 1,610 (range 148 to 7680). All patients
      underwent laparoscopic cholecystectomy during the same hospital admission for
      biliary pancreatitis, with the mean time of operation being 5.5 days from
      admission. Operative time averaged 123 minutes (range 60-220 minutes).
      Intraoperative cholangiography was obtained in 76 per cent of patients. Three
      patients had choledocholithiasis on intraoperative cholangiography and were
      treated with choledochoscopy, laparoscopic common bile duct exploration, and
      saline flushing of the duct. The mean length of hospital stay was 11 days (range
      5-32 days). There were seven postoperative complications requiring prolonged
      hospitalization with all but one treated non-operatively. One patient with a
      preoperative Ranson score of 6 developed necrotizing pancreatitis and
      subsequently required operative pancreatic debridement and drainage. There were
      no deaths in this series and no postoperative wound infections. The average
      recovery period for return to work was 2 weeks. These statistics compare
      favorably with literature reports for open cholecystectomy in biliary
      pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506012
TI  - Resuscitation in uncontrolled hemorrhage.
AB  - Fluid resuscitation is considered to be an integral component of the management
      of hemorrhagic shock. Numerous experimental studies of hypovolemic shock have
      confirmed the value of volume infusions, but in these models the rate, volume,
      and duration of bleeding are carefully controlled. The results of such studies
      may not be applicable to clinical hemorrhage, in which bleeding continues
      unabated. Male Sprague-Dawley rats weighing 250 to 390 g were anesthetized, and a
      femoral artery and vein were cannulated for constant blood pressure monitoring
      and fluid infusion. Through a midline abdominal incision, the distal ileocolic
      artery and vein were transected and allowed to bleed freely into the peritoneal
      cavity. The abdomen was closed and the animals were randomized to one of five
      groups: no resuscitation; small volume lactated Ringer's solution; large volume
      lactated Ringer's; small volume hetastarch; or large volume hetastarch. After 3
      hours or at spontaneous death, blood was withdrawn to measure hematocrit,
      platelet count, and fibrinogen. Blood in the peritoneal cavity was collected and
      measured. Animals that received either lactated Ringer's or hetastarch had more
      bleeding into the peritoneal cavity and a greater dilution of clotting factors
      than animals that received no resuscitation fluids (P < 0.05). In addition,
      survival was highest in unresuscitated animals, although only the small volume
      hetastarch group had a significantly lower survival when independently compared
      with no resuscitation (P < 0.05). These results suggest that in traumatic shock,
      fluid resuscitation should be minimized until mechanical control of bleeding can
      be achieved.

PMID- 7506014
TI  - Cross-resistance to purine analogs in hairy cell leukemia.

PMID- 7506013
TI  - Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to
      systemic sclerosis. A multicenter, placebo-controlled, double-blind study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of iloprost, a prostacyclin
      analog, administered intravenously in patients with Raynaud phenomenon secondary
      to systemic sclerosis. DESIGN: Multicenter, randomized, parallel placebo
      controlled, double-blind study. SETTING: University medical centers. PATIENTS:
      131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years.
      INTERVENTION: Patients were randomly assigned to receive one of two parallel
      treatments of five daily sequential, 6-hour intravenous infusions of iloprost
      (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo.
      MEASUREMENTS: Frequency of Raynaud attacks, Raynaud severity score, physician's
      overall rating of treatment effect, and digital cutaneous lesion healing.
      RESULTS: Of the 131 patients enrolled, 126 completed the 5-day infusion and 114
      (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly
      assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly
      number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P
      = 0.005). In addition, the mean percentage of improvement in a global Raynaud
      severity score during the entire 9-week follow-up was greater in patients given
      iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The
      physician's overall rating of treatment effect showed greater improvement with
      iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and
      week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients
      receiving iloprost had 50% or more lesions heal compared with those given placebo
      (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving
      iloprost had one or more side effects compared with 38 (57%) of the patients
      receiving placebo. CONCLUSION: Iloprost is effective for the short-term
      palliation of severe Raynaud phenomenon in patients with systemic sclerosis.

PMID- 7506015
TI  - Zymomonas mobilis cell viability: measurement method comparison.
AB  - Comparison of three different cell viability methods: slide count, plate count
      and methylene blue staining techniques, applied on Zymomonas mobilis cultures,
      was performed. The slide technique proved to be faster and more accurate than the
      plate count method, and both of them far more reliable than the standard
      methylene blue method which constantly overestimated the Zymomonas cell
      viability. The slide technique is advantageous also because it gives information
      on the cell morphology changes, notably the abnormal cell elongation, in the
      ethanol fermentation.

PMID- 7506017
TI  - The effect of nonionic detergents on the activity and/or stability of rat brain
      nitric oxide synthase.
AB  - The results of this study indicate that the addition of low concentrations of a
      nonionic detergent such as those represented by the Tween, Brij, or Triton
      classes causes an apparent activation of nitric oxide synthase. It is possible
      that this apparent activation is due to the ability of these detergents to
      stabilize the protein. The stabilizing influence of the detergents may be a
      result of inhibiting the dissociation of the dimeric protein into monomers or the
      dissociation of an essential cofactor or prosthetic group from the active enzyme.
      Regardless of the mechanism of action, the addition of low concentrations of
      nonionic detergents results in longer and increased nitric oxide synthase
      activity and may be an important tool for those involved in enzymological studies
      of nitric oxide synthase.

PMID- 7506016
TI  - Protein kinase C is not involved in Ah receptor transformation and DNA binding.
AB  - Induction of cytochrome P4501A1 by 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD) is
      mediated by the Ah receptor (AhR) complex, a ligand-dependent DNA-binding
      transactivator. Recently a role for protein kinase C (PKC) in the induction
      response has been reported in which PKC or a related kinase positively modulates
      AhR activity. We have examined the role of PKC by determining the effect of two
      nonspecific PKC inhibitors, H7 and staurosporine, and one specific PKC inhibitor,
      calphostin c, on AhR functionality. Although no kinase activity was detectable in
      cytosol, under the conditions used for our assays, AhR transformation and DNA
      binding still occurred. Addition of relatively high concentrations of the kinase
      inhibitors also had no significant effect on TCDD:AhR:DRE complex formation.
      Thus, our results indicate that protein kinase activity does not appear to be
      necessary for TCDD-dependent AhR transformation and DNA binding and they imply
      that protein kinases must play a role in another step(s) in the AhR-dependent
      mechanism of P4501A1 induction.

PMID- 7506018
TI  - An immunohistochemical and histochemical study of cytokeratin, involucrin and
      transglutaminase in seborrhoeic keratosis.
AB  - The mode of differentiation of seborrhoeic keratoses was investigated by
      immunohistochemical staining using cytokeratin (CK) polypeptide-specific
      monoclonal antibodies and an antibody specific for the particulate form of
      epidermal transglutaminase (ETgase), and by applying an anti-human involucrin
      serum. The role played by (E)Tgase was further evaluated using an activity assay
      based on the covalent attachment of monodansylcadaverine. Samples of uninvolved
      epidermis served as reference tissue. CK reactivities suggested that seborrhoeic
      keratoses is a hyperproliferative disease with an epidermal CK composition. CK5
      and CK14 were prominent markers of basal and basaloid keratinocytes, whereas a
      decrease in staining occurred in advanced maturation stages and areas of terminal
      keratinization. In contrast, CK1 and CK10 were prominent markers of suprabasaloid
      differentiation stages and produced complementary stainings to those of CK5 and
      14. Generally, CK10 staining was more impressive than CK1 staining and seemed to
      start before CK1 staining. In contrast to CK10 staining, cornified areas lost CK1
      reactivity. These staining patterns were similar to those observed in uninvolved
      reference tissues. The epidermal CK subset was further supplemented with the
      'hyperproliferative' CK6 and 16 which occur sequentially. Positive staining for
      CK6 was noted from basal and proximal basaloid cells onwards, whereas distal
      basaloid cells additionally showed CK16 staining. The presence of other non
      epidermal CK polypeptides could not be shown. The competence for other
      differentiation markers belonging to the group of (E)Tgase and cornifying cell
      membranes also evolved with a typical epidermal pattern. (E)Tgase activity was
      restricted to advanced and terminal stages of keratinization and was dual in
      nature, i.e. a diffuse cytoplasmic staining occurred together with a prominent
      staining of cornifying cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506019
TI  - Effect of follicular fluid on the kinetics of human sperm acrosome reaction in
      vitro.
AB  - The purpose of the present study was to evaluate the kinetics of human sperm
      acrosome reaction in vitro using the triple stain technique. Acrosome reaction
      was studied in sperm samples from 16 fertile men 2, 6, and 9 h after ejaculation,
      following incubation in culture medium (CM; Ham's F-10), with a mixture of CM and
      follicular fluid (FF), or with FF only. Incubation of sperm samples without the
      influence of any medium served as control. The highest proportion of living
      acrosome-reacted sperm after a 2-h incubation period occurred in samples
      incubated with FF (18%), followed by samples incubated with the mixture (15.2%),
      and then with CM (11.8%). The proportion of living sperm that had undergone the
      acrosome reaction in the control group was significantly lower (5.7%, p < 0.05).
      After 6 h of incubation, live acrosome-reacted sperm in FF had increased to 39%,
      in the mixture to 35.5%, and in CM to 30.5%, whereas in the control group the
      increase was only 6.3% (p < 0.05). After 9 h of incubation, the percentage of
      living reacted sperm showed a decline compared with the percentage at 6 h. This
      decline was greater in samples incubated with FF (from 39 to 19.8%) than in
      samples incubated with the mixture (from 35.5 to 23.6%). Samples incubated in CM
      only showed a small decrease from 30.5 to 28.4%, while in the control group this
      percentage decreased from 6.3 to 2.3%. In conclusion, incubation of sperm in
      suitable media favorably influences the acrosome reaction, inducing an increase
      in the percentage of live acrosome-reacted sperm.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7506020
TI  - The effect of incisional infiltration of bupivacaine upon pain and respiratory
      function following open cholecystectomy.
AB  - A controlled, prospective, double-blind trial of wound infiltration with
      bupivacaine in elective open cholecystectomy was performed to determine if this
      was an effective method of pain relief and reduced respiratory complications.
      Additionally, dextran was added to the bupivacaine in an attempt to prolong the
      effect. The solutions used were, bupivacaine alone 0.25% (n = 14), bupivacaine
      0.25% with dextran 70 (n = 16) and saline (n = 16) as a control. To determine the
      effect of each solution, the subjects were assessed for pain perception and
      respiratory function before and after surgery. Pain was assessed using a visual
      analogue scale and narcotic usage, and respiratory function was assessed by
      spirometry, chest X-rays and arterial blood gases. The study did not demonstrate
      any objective improvement in either pain relief or respiratory function. This may
      reflect inadequate infiltration by the surgeons in the study or that infiltration
      should have been performed prior to incision.

PMID- 7506021
TI  - Perceived risks of postoperative analgesia.
AB  - This survey aimed to determine what type of information patients want about the
      risks of postoperative pain management and whether this corresponded to the
      information that doctors and nurses wished to provide. Seventy-four patients
      scheduled for elective surgery, 50 nurses and 48 doctors completed a
      questionnaire asking about perceived risks of analgesia, level of acceptable risk
      and information that should be provided to patients. Compared to doctors and
      nurses, patients underestimated the risks associated with postoperative pain
      relief, except for the risk of drug addiction, which they rated higher. Ninety
      one per cent of patients wanted information about the side effects of analgesia.
      The preferred means of obtaining this information was by discussion with their
      surgeon or anaesthetist. Doctors were willing to accept a greater risk of minor
      side effects to achieve excellent pain relief than were patients. In contrast,
      patients were willing to accept a greater risk of serious side effects. The
      results obtained in this survey will facilitate the preparation of guidelines for
      obtaining informed consent from patients to receive postoperative analgesia.

PMID- 7506022
TI  - The molecular biology of taste transduction.
AB  - Taste cells respond to a wide variety of chemical stimuli: certain ions are
      perceived as salty (Na+) or sour (H+); other small molecules are perceived as
      sweet (sugars) and bitter (alkaloids). Taste has evolutionary value allowing
      animals to respond positively (to sweet carbohydrates and salty NaCl) or
      aversively (to bitter poisons and corrosive acids). Recently, some of the
      proteins involved in taste transduction have been cloned. Several different G
      proteins have been identified and cloned from taste tissue: gustducin is a taste
      cell specific G protein closely related to the transducins. Work is under way to
      clone additional components of the taste transduction pathways. The combination
      of electrophysiology, biochemistry and molecular biology is being used to
      characterize taste receptor cells and their sensory transduction mechanisms.

PMID- 7506024
TI  - The p53-mdm2 autoregulatory feedback loop: a paradigm for the regulation of
      growth control by p53?

PMID- 7506023
TI  - Localized RNAs and their functions.
AB  - The eukaryotic cell is partitioned by membranes into spatially and functionally
      discrete subcellular organelles. In addition, the cytoplasm itself is partitioned
      into discrete subregions that carry out specific functions. Such compartmentation
      can be achieved by localizing proteins and RNAs to different subcellular regions.
      This review will focus on localized RNAs, with a particular emphasis on RNA
      localization mechanisms and on the possible biological functions of localization
      of these RNAs. In recent years, an increasing number of localized RNAs have been
      identified in a variety of cell types among many animal species. Emphasis here
      will be on localized RNAs in the most intensively studied systems-Drosophila and
      Xenopus eggs and early embryos.

PMID- 7506025
TI  - Importance of pharmacodynamics in the in vitro antiproliferative activity of the
      antifolates methotrexate and 10-ethyl-10-deazaaminopterin against human head and
      neck squamous cell carcinoma.
AB  - The pharmacodynamic profiles of methotrexate (MTX) and 10-ethyl-10
      deazaaminopterin (10-EdAM) were determined in three head and neck squamous cell
      carcinoma (HNSCC) cell lines. Cell growth inhibition was tested using a semi
      automated 96-well based proliferation assay, the sulforhodamine B (SRB) assay.
      Drug concentrations ranged from 10(-5) to 10(-9) M, with exposure periods of 4,
      24, 48, 72 and 96 hr. The SRB-test was performed after each of these periods of
      continuous exposure and after an additional period of 24 and 48 hr in drug-free
      medium. Without a drug-free period the IC50 values strongly depended on the time
      of exposure. For example, with respect to MTX, IC50 values at 24 hr ranged from
      2.9 (UM-SCC-14C) to over 10 microM (UM-SCC-22B and -11B), but when exposed
      continuously for 96 hr, IC50 values varied between 0.039 and 0.1 microM. 10-EdAM
      followed a similar sensitivity pattern with 5-20-fold lower IC50 values. The
      minimal time to achieve significant growth inhibition varied between the cell
      lines, < 24 hr for UM-SCC-14C, > 24 and > 48 hr for UM-SCC-11B and -22B,
      respectively. The cell lines also varied with respect to growth behaviour when
      placed in drug-free medium for an additional period. Growth of UM-SCC-14C cells
      was recovered significantly after removing the drug, whereas UM-SCC-22B showed a
      different pattern: when cultured for over 48 hr, cell growth was strongly
      inhibited, independent of the drug being removed. This variable pattern of
      sensitivity could be correlated with the capacity of the cells to form
      polyglutamate derivatives. After 24 hr, drug accumulation was at least three
      times lower in UM-SCC-14C than in both other cell lines. The low level of
      antifolate accumulation in UM-SCC-14C is in line with the recovery from growth
      inhibition at culture in drug-free medium, while the persistent growth inhibition
      observed in UM-SCC-22B agrees with the intracellular accumulation of higher
      polyglutamates. In conclusion, these experiments show that the pharmacodynamic
      profile varies between HNSCC cell lines and plays an important role in the growth
      inhibition by antifolates. Both exposure time and the intrinsic capacity to
      synthesize polyglutamates are important factors in the sensitivity of HNSCC to
      antifolate drugs.

PMID- 7506026
TI  - Determinants of the disparate antitumor activities of (6R)-5,10-dideaza-5,6,7,8
      tetrahydrofolate and methotrexate toward human lymphoblastic leukemia cells,
      characterized by severely impaired antifolate membrane transport.
AB  - We previously reported (Matherly et al., J Biol Chem 267: 23253-23260, 1992) that
      impaired methotrexate transport in a drug-resistant CCRF-CEM variant (CEM/MTX)
      involved the synthesis of a structurally altered isoform of the "classical"
      carrier for methotrexate and related derivatives. Although CEM/MTX cells were
      highly resistant (162- to 300-fold) to assorted antifolate substrates for the
      classical transporter, including methotrexate, aminopterin, 10-ethyl-10
      deazaaminopterin, ICI D1694, and 1843U89, they were only 3.6-fold resistant to
      (6R)-5,10-dideaza-5,6,7,8-tetrahydrofolate (DDATHF). These divergent antifolate
      sensitivities were not associated with appreciable differences in the levels of
      dihydrofolate reductase, thymidylate synthase, and 5'-phosphoribosylglycinamide
      (GAR) transformylase, or the expression of a high affinity membrane folate
      binding protein receptor in either line. The initial rate of [14C]DDATHF influx
      was increased 2.9-fold over that for [3H]methotrexate in parental cells (at 2
      microM). Whereas [14C]DDATHF initial uptake was, likewise, increased over
      [3H]methotrexate in CEM/MTX cells (5.3-fold), influx of both compounds was
      impaired substantially (95-97%). For the parent, influx of [14C]DDATHF was
      inhibited by substrates for the classical transporter including unlabeled DDATHF,
      methotrexate, (6R,S)-5-formyl tetrahydrofolate, 10-ethyl-10-deazaaminopterin, ICI
      D1694, 1843U89, and folic acid. The synthesis of a modified transporter in
      CEM/MTX cells was accompanied by significant changes in the binding of all these
      transport substrates. In spite of its impaired transport, [14C]DDATHF (at 2
      microM), unlike methotrexate, continued to accumulate in CEM/MTX cells,
      eventually reaching 62% of the parental drug levels after 4 hr. At this time, 53%
      (parent) and 71% (CEM/MTX) of the intracellular radioactivity from [14C]DDATHF
      was identified as polyglutamates. DDATHF polyglutamates in CEM/MTX cells after 4
      hr reached 90% of the levels measured in parental cells. While significant levels
      of methotrexate polyglutamates were detected in the parental line, methotrexate
      polyglutamylation was negligible in intact CEM/MTX cells. The specific activity
      of folylpolyglutamate synthetase was measured in cell-free extracts from parental
      and CEM/MTX cells using aminopterin, methotrexate, and DDATHF as substrates; in
      each case, CEM/MTX cells showed 2-fold higher enzyme activity than parental
      cells. These data show that even for tumor cells with severely impaired
      antifolate transport, the extensive conversion of DDATHF to polyglutamyl forms
      required for GAR transformylase inhibition preserves high levels of antitumor
      activity.

PMID- 7506027
TI  - Identification of the amino acid in the human immunodeficiency virus type 1
      reverse transcriptase involved in the pyrophosphate binding of antiviral
      nucleoside triphosphate analogs and phosphonoformate. Implications for multiple
      drug resistance.
AB  - A recombinant clone of human immunodeficiency virus type 1 reverse transcriptase
      (HIV-1 RT) with reduced sensitivity to 3'-azido-3'-deoxythymidine 5'-triphosphate
      (AZTTP) and phosphonoformate (PFA), a pyrophosphate analog, has been obtained
      from the RNA of HTLV-IIIB infected cells using the polymerase chain reaction. The
      mutant HIV-1 RT retained polymerase activity and was cross-resistant to
      triphosphate forms of other nucleoside analogs including 2',3'-dideoxycytidine 5'
      triphosphate, 2',3'-dideoxyadenosine 5'-triphosphate, and 3'-deoxy-2',3'
      didehydrothymidine 5'-triphosphate (D4TTP), but remained sensitive to the non
      nucleoside HIV-1 RT inhibitors, such as nevirapine and TIBO R82150. Sequence
      analysis of the mutant HIV-1 RT revealed a single amino acid substitution (Val-
      >Ala) at amino acid 90. The substitution of amino acid 90 by the closely related
      amino acids, such as Thr and Gly, also showed decreased sensitivity to AZTTP,
      D4TTP, and PFA. All these mutations at amino acid 90 also caused an alteration of
      Km for thymidine triphosphate. These results suggest that Val at this site plays
      a role in determining the interaction of the HIV-1 RT enzyme with the
      pyrophosphate group of deoxynucleoside triphosphate (dNTP) and that the
      hydrophobicity of the amino acid at this position was the most important
      determinant in the binding of HIV-1 RT to dNTP.

PMID- 7506029
TI  - Effect of lovastatin on cell surface expression of Fc receptors or CD14 antigen
      in human monocytes.
AB  - Lovastatin is a widely used anticholesterolemic drug which exercises its effect
      by inhibiting hepatic cholesterol synthesis and up-regulating low density
      lipoprotein (LDL) receptors. In the present study, we determined that the drug
      has no adverse effects on the expression of three cell surface antigens of human
      monocytes, i.e. high affinity Fc receptors (Fc gamma RI), low affinity Fc
      receptors (Fc gamma RII) and CD14 antigen. We have shown previously these
      antigens are regulated by cholesterol and lipoproteins. At 0.5 micrograms/mL of
      culture medium, lovastatin did not reduce the percentage of receptor-positive
      cells or the average number of receptor molecules per cell. These observations
      add to the attractiveness of the drug as an anticholesterolemic agent and also
      indicate that endogenous cholesterol biosynthesis by monocytes is not required
      for expression of Fc gamma RI, Fc gamma RII, or CD14.

PMID- 7506028
TI  - Quercetin-induced expression of rat mast cell protease II and accumulation of
      secretory granules in rat basophilic leukemia cells.
AB  - Rat basophilic leukemia (RBL) cells are considered to be similar to bone-marrow
      derived mast cells and to mucosal mast cells (MMC), the latter of which may be
      involved in inflammatory bowel diseases. RBL cells are not able to accumulate
      histamine and secretory granules under regular growing conditions. Here we show
      that the flavonoid quercetin, which inhibits mast cell secretion of histamine,
      also inhibited RBL cell proliferation and constitutive histamine release while it
      induced synthesis of rat mast cell protease (RMCP) II and triggered processes
      leading to accumulation of secretory granules. Cell viability was also retained
      in the presence of quercetin, whereas untreated cells did not survive past 6 days
      of growth. Quercetin did not affect the expression of mRNA for alpha-subunit of
      immunoglobulin E (IgE) receptor, but led to increased expression of mRNA for, and
      synthesis of RMCP II, which is a marker protein for MMC. Many of these granules
      showed metachromasia with toluidine blue after 3 days of growth, stained red with
      alcian blue counterstained with safranin after 8 days of growth, and contained
      electron dense material. Our results suggest that RBL cells have the capacity to
      progress to a more mature state and may lend themselves to further analysis of a
      growth regulator(s) with action similar to that of quercetin.

PMID- 7506030
TI  - [Computerized structural analysis of O-specific polysaccharides O1A, O1B, and O1C
      from Escherichia coli].
AB  - A computer evaluation of 13C-NMR data for the title polysaccharides based on the
      monosaccharide and methylation analysis data led to the structure of the
      repeating unit of the O1A polysaccharide as well as to several probable
      structures of the O1C polysaccharide, of which the correct one was inferred by
      means of a single NOE experiment. The analysis of the spectrum of the O1B
      polysaccharide was unsuccessful, due to the presence in its structure of the
      fragment alpha-L-Rha-(1-->2)-alpha-D-Gal-(1-->3)-D-GlcNAc with the terminal (1-
      >2)-linkage, whose spectral data could not be calculated by additive schemes
      using only glycosylation effects. However in reevaluation of the O1B spectral
      data by taking into account the deviations from additivities of the chemical
      shifts values in spectra of the related trisaccharides, to reveal the most
      probable structure of the O1B's repeating unit. [formula: see text]

PMID- 7506031
TI  - [Structure of the repeating unit of O-specific polysaccharide from Vibrio
      fluvialis].
AB  - O-Specific polysaccharide of Vibrio fluvialis, strain AQ-0002B, is built up to
      pentasaccharide repeating units contained of D-mannose, 2-acetamido-2-deoxy-D
      glucose, 2-acetamido-2-deoxy-D-galactose, D-galacturonic acid and 3-0-[(R)-1'
      carboxyethyl]-L-rhamnose (rhamnoactylic acid, Rha3Lac) residues. On the basis of
      methylation studies, solvolysis with HF, Smith degradation, 1H and 13C NMR
      spectroscopy including homo- and heteronuclear correlation spectroscopy and NOE
      experiments, the following structure was suggested for the polysaccharide
      repeating unit: [formula: see text]

PMID- 7506032
TI  - Antibodies from alcoholics, ethanol-fed rats and a rabbit immunised with proteins
      modified by acetaldehyde in vitro react with liver cytosolic proteins from
      ethanol-fed rats.
AB  - In previous studies we have shown that ethanol-fed rats generate antibodies
      reactive with proteins modified by acetaldehyde in vitro and that their livers
      contain proteins modified by acetaldehyde. In this study we demonstrate that the
      antibodies from these animals react with the modified proteins found in their
      livers. Furthermore, when the antibodies reactive with specific proteins were
      isolated, they were found to react with all of the modified proteins detected by
      the whole serum. This suggests that all of the proteins modified by acetaldehyde
      in vivo carry the same or similar epitope(s). In addition, antibodies from
      alcoholics and a rabbit immunised with proteins modified by acetaldehyde in vitro
      also reacted with the liver cytosolic proteins from ethanol-fed rats. Therefore
      it appears that similar epitopes are generated in alcoholics as a result of
      ethanol misuse, in rat liver due to prolonged ethanol feeding and by the in vitro
      modification procedure used to produce the immunogen for the rabbit.

PMID- 7506033
TI  - Interaction of the natural anti-Gal antibody with alpha-galactosyl epitopes: a
      major obstacle for xenotransplantation in humans.
AB  - Cells of nonprimate mammals express an abundance of the carbohydrate structure
      Gal alpha 1-3 Gal beta 1-4 GlcNac-R (termed the alpha-galactosyl epitope). The
      natural anti-Gal antibody, which interacts specifically with alpha-galactosyl
      epitopes, is present in high concentrations in all humans. Here, Uri Galili
      argues that the interaction between anti-Gal in the serum and alpha-galactosyl
      epitopes on cells of nonprimate grafts may act as an immunological barrier which
      prevents xenotransplantation.

PMID- 7506034
TI  - Costimulation of T cells for tumor immunity.
AB  - Tumor specific antigens can be demonstrated on many neoplasms by immunization and
      challenge experiments; however, these antigens do not normally elicit a
      sufficiently strong immune response to prevent tumor growth in immunocompetent
      hosts. Recent studies have demonstrated that efficient activation of T cells
      requires costimulation of the CD28 receptor via the B7 molecule on antigen
      presenting cells. Inadequate costimulation of tumor-reactive T cells may
      contribute to the fact that antigenic tumors are not normally rejected by the
      immune system, and weak anti-tumor immune responses may be amplified by
      upregulation of CD28 triggering.

PMID- 7506035
TI  - Circulating adhesion molecules in disease.
AB  - The demonstration of soluble isoforms of adhesion molecules has added a layer of
      complexity of our understanding of lymphoid-endothelial cell interactions. This
      is especially true in the light of observations which show levels of these
      isoforms to be raised during disease processes. Here, Andrew Gearing and Walter
      Newman review the evidence that increased levels of circulating, soluble adhesion
      molecules may be a key to understanding the prognosis and pathology of certain
      diseases.

PMID- 7506036
TI  - Soluble CD14 antigen in patients with AIDS.

PMID- 7506037
TI  - CD40 ligand and its role in X-linked hyper-IgM syndrome.
AB  - CD40 ligand (CD40L) on activated T cells binding to CD40 on B cells is of
      critical importance for Ig heavy-chain switching and rescue of B cells from
      apoptosis after somatic mutation in the germinal centre. Mutations in the CD40L
      gene are now known to cause X-linked hyper-IgM syndrome (HIGM1), an
      immunodeficiency characterized by the absence of serum IgG, IgA and IgE. In this
      review, we discuss how basic and clinical immunology have combined to provide
      major insights into the function of CD40 in T-B cell collaboration.

PMID- 7506038
TI  - Transcriptional regulators of expression of K#16, the disease-associated keratin.
AB  - In most malignant and benign skin diseases, the normal pattern of keratin
      expression is altered. Among other phenotypic changes, the expression of
      hyperproliferation- and activation-associated keratins K#16 and K#6 is induced.
      Because the molecular mechanisms and the nuclear regulators involved in this
      induction are unknown, we have characterized the transcriptional regulators of
      expression of the keratin K#16 promoter. Our previous studies have shown that the
      transcription of K#16 is strongly and specifically induced in epidermal
      keratinocytes by epidermal growth factor (EGF), through the EGF-responsive
      element (RE). In the present work, using an electrophoretic mobility-shift assay,
      we have found several nuclear protein binding sites that have been identified as
      an Sp1 site, an AP2 site, the EGF-RE, and an enhancer element. The function of
      each site was assessed in transfection assays using specific deletions. Both the
      Sp1 and EGF-RE sites are essential for K#16 promoter activity. The site that
      functions as an independent enhancer, E, was found adjacent to and interacting
      with a sequence recognized by the AP2 transcription factor. This knowledge of the
      nuclear regulators of expression of the disease-associated K#16 keratin provides
      insight into the molecular parameters that might be important in skin diseases.

PMID- 7506039
TI  - Distribution of dopamine-immunoreactive neurons and their relationships to
      transmitter and hypothalamic hormone-immunoreactive neuronal systems in the rat
      mediobasal hypothalamus. A morphometric and microdensitometric analysis.
AB  - A morphometric and microdensitometric characterization of the dopamine neurons of
      the mediobasal hypothalamus and their relationships with several other chemically
      identified systems, including putative tyrosine hydroxylase-positive/dopamine
      negative neurons, was carried out after visualization of dopamine content by both
      immunocytochemistry and the Falck-Hillarp technique. Quantitative assessment of
      co-existence demonstrated that more than 95% of dopamine-immunoreactive neurons
      also contained tyrosine hydroxylase immunoreactivity and more than 90% of growth
      hormone-releasing factor-immunoreactive neurons also contained tyrosine
      hydroxylase immunoreactivity. Morphometric and densitometric analysis of
      dopamine, tyrosine hydroxylase and growth hormone-releasing factor-immunoreactive
      neurons in the arcuate nucleus showed that dopamine/tyrosine hydroxylase
      containing and growth hormone-releasing factor/tyrosine hydroxylase-containing
      neuronal populations are two largely segregated cell groups with specific
      localization in the arcuate region, rostrocaudal extension and tyrosine
      hydroxylase-immunoreactivity content. Morphometric characteristics of dopamine
      immunoreactive neurons were shown to be equivalent to those of catecholamine
      fluorescent cell bodies in the arcuate region. In addition, a cell group lacking
      detectable catecholamine fluorescence in normal animals but accumulating L-DOPA
      after peripheral loading was identified and characterized from a morphometric
      standpoint in the ventral premammillary nucleus. Quantitative analysis of nerve
      terminal co-distribution in the median eminence revealed significant correlations
      between dopamine and other transmitter or neurohormone systems, such as gamma
      aminobutyric acid, galanin, luteinizing hormone-releasing hormone, in specific
      subregions of the palissade zone. These data point to discrete subregions of the
      median eminence, which have been called 'medianosomes', as main sites of
      interactions between transmitter-identified nerve terminal systems in the control
      of hypothalamic hormone release.

PMID- 7506040
TI  - Regulation of the response to bacterial lipopolysaccharide by endogenous and
      exogenous lipopolysaccharide binding proteins.
AB  - Bactericidal/permeability-increasing protein (BPI) is a natural constituent of
      human neutrophils. Recombinant BPI has been shown to bind to bacterial
      lipopolysaccharide (LPS), and to neutralize the ability of LPS to stimulate
      inflammatory cells in vitro and in vivo. BPI shares sequence homology and
      immunocrossreactivity with another endogenous LPS binding protein,
      lipopolysaccharide binding protein (LBP). Despite the homology, these proteins
      have opposite effects on LPS. LBP mediates cell activation by low, otherwise
      nonstimulatory concentrations, while BPI neutralizes LPS bioactivity. Exogenous
      LPS binding proteins in the form of monoclonal antibodies have been developed
      with the goal of generating antiendotoxin therapeutics to treat gram-negative
      sepsis and related syndromes. Here we show that LPS-binding and neutralizing
      properties of BPI compare favorably with two monoclonal antibodies tested, HA-1A
      and XMMEN-OE5. BPI also competes effectively with LBP for LPS. Thus, BPI may
      represent an endogenous LPS-regulatory molecule suitable for use as a potent
      antiendotoxin therapeutic.

PMID- 7506042
TI  - Initial characterization of endothelial mitogens produced by bovine corpora lutea
      from the estrous cycle.
AB  - To further characterize mitogenic factor(s) present in luteal extracts or luteal
      explant conditioned media (LCM), bovine corpora lutea (CL) were homogenized or
      incubated in explant culture, respectively. After evaluation of luteal extracts
      and LCM by using an endothelial cell proliferation bioassay, mitogenic activity
      was characterized by immunoneutralization with antibodies against heparin-binding
      (fibroblast) growth factor (HBGF) 1 or 2. LCM also were subjected to
      ultrafiltration, as well as anion-exchange, cation-exchange, and heparin-affinity
      chromatography. The presence of HBGF-2 in LCM also was evaluated by using a dot
      immunoblot assay. Extracts of luteal tissues and LCM stimulated (P < 0.05)
      proliferation of endothelial cells in a dose-dependent manner. Mitogenic activity
      of luteal extracts and LCM was decreased (P < 0.05) by treatment with specific
      antibodies against HBGF-2 or HBGF-1. LCM also contained immunoreactive HBGF-2.
      The mitogenic activity bound to anion exchangers, phenyl-Sepharose, and heparin
      agarose, but not to cation exchangers, indicating that endothelial mitogenic
      activity is anionic at neutral pH, has some hydrophobic characteristics, and
      belongs to the HBGF family of proteins. Following ultrafiltration, endothelial
      mitogenic activity was retained by membranes having a 30,000 or 100,000 molecular
      weight cutoff. In addition, LCM was resolved into four peaks of heparin-binding
      endothelial mitogenic activity, each with a different affinity for heparin. These
      data demonstrate that bovine CL contain and produce endothelial mitogens of large
      molecular size, which may be important regulators of luteal function. These
      endothelial mitogens are heparin-binding and anionic at neutral pH.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7506041
TI  - Purification and characterization of the plasminogen activator inhibitors PAI-1,
      PAI-2, and PN-1 from the human glioblastoma U138.
AB  - This investigation presents data which indicate that the plasminogen activator
      inhibitor (PAI) activity secreted from U138 cells is composed of three separate
      PAIs: PAI-1, PAI-2, and PN-1. It was demonstrated that the U138 PAI-1-like
      protein had an apparent molecular mass of 50 kilodaltons (kDa) and was purified
      to apparent homogeneity by elution from an anti-PAI-1 immunoaffinity column.
      These fractions were also reactive with a second anti-PAI-1 monoclonal antibody
      using immunoblotting techniques. Northern blot analysis of RNA isolated from
      unstimulated U138 cells demonstrated positive hybridization with the cDNA
      specific for human PAI-1. The U138 PAI-2-like protein was adherent to an anti-PAI
      2 immunoaffinity column and was demonstrated to be nonadherent to concanavalin A
      agarose, heparin-Sepharose, and the anti-PAI-1 immunoaffinity column. The eluted
      U138 PAI-2-like protein was demonstrated to have an apparent molecular mass of 60
      kDa and was also reactive with a second anti-PAI-2 monoclonal antibody using
      immunoblotting techniques. Further, the cDNA specific for PAI-2 was demonstrated
      to hybridize to a 2.5-kilobase message from RNA isolated from U138 cells. A third
      PAI was detected that was nonadherent to concanavalin A-agarose and both of the
      anti-PAI columns. This 50-kDa PAI was adherent to heparin-Sepharose and thrombin
      agarose columns, and was not reactive with any antibodies for either PAI-1 or PAI
      2. Northern blot analysis of U138 RNA demonstrated positive hybridization with an
      oligodeoxynucleotide specific for PN-1. This investigation demonstrates with
      biochemical, immunological, and molecular data that the U138 glioblastoma
      constitutively produces three PAIs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506043
TI  - Selective modulation of desensitization at AMPA versus kainate receptors by
      cyclothiazide and concanavalin A.
AB  - Potentiation by cyclothiazide of recombinant glutamate receptor responses in
      Xenopus oocytes showed absolute selectivity for AMPA versus kainate receptors. In
      contrast, concanavalin A strongly potentiated responses at kainate but not AMPA
      receptors. Rapid desensitization in HEK 293 cells transfected with AMPA receptors
      was blocked by cyclothiazide, but only weakly attenuated by concanavalin A.
      Desensitization at kainate receptors was blocked by concanavalin A but unaffected
      by cyclothiazide. Selective effects of these modulators following coexpression of
      subunits from different families suggest independent assembly of functional AMPA
      and kainate receptors. Northern blot analysis of mRNA for dorsal root ganglia
      revealed a predominant expression of GluR5, indicating that modulation of
      desensitization by concanavalin A but not cyclothiazide in sensory neurons
      accurately predicts subunit expression for native glutamate receptors.

PMID- 7506044
TI  - Different glutamate receptor channels mediate fast excitatory synaptic currents
      in inhibitory and excitatory cortical neurons.
AB  - Spontaneous excitatory postsynaptic currents (sEPSCs) and responses to rapid
      application of glutamate were recorded in excitatory spiny, pyramidal neurons and
      compared with those recorded in inhibitory aspiny interneurons. The sEPSC decay
      time constant was faster in aspiny interneurons (2.5 ms) compared with pyramidal
      neurons (4.6 ms). The decay time constant in response to a brief application (1
      ms) of glutamate (10 mM) in patches excised from pyramidal and aspiny
      interneurons were similar (1.9 and 2.7 ms, respectively). However, the rate of
      desensitization was faster in patches from interneurons compared with pyramidal
      neurons (3.4 and 12.0 ms, respectively). In addition, single-channel conductance
      was larger in aspiny interneurons (27 pS) compared with pyramidal neurons (9 pS).
      These results indicate that pyramidal neurons and aspiny interneurons express
      different non-N-methyl-D-aspartate receptors and that selective desensitization
      of interneuron receptors may contribute to depression of inhibition.

PMID- 7506045
TI  - Induction of cerebellar long-term depression in culture requires postsynaptic
      action of sodium ions.
AB  - Cerebellar long-term depression (LTD) is a persistent attenuation of the parallel
      fiber-Purkinje neuron (PF-PN) synapse induced by conjunctive stimulation of PF
      and climbing fiber (CF) inputs. A similar phenomenon is seen in the voltage
      clamped PN in tissue culture when iontophoretic quisqualate application and PN
      depolarization are substituted for PF and CF stimulation, respectively. In this
      model, LTD induction requires activation of both AMPA and metabotropic receptors,
      together with PN depolarization. We have sought to determine the role of the AMPA
      receptor in LTD induction. The AMPA receptor does not appear to exert its effect
      by directly gating Ca2+ influx. Replacement of external Na+ during
      quisqualate/depolarization conjunction with permeant ions caused a blockade of
      LTD induction, suggesting that Na+ influx through the AMPA-associated channel is
      necessary for this process. Similarly, pairing quisqualate pulses with
      depolarizing steps near ENa also failed to induce LTD. The present results
      indicate that postsynaptic Na+ influx is necessary for LTD induction. While a
      portion of the relevant Na+ influx is provided by voltage-gated channels, the
      AMPA-associated ion channel is most important in this regard.

PMID- 7506047
TI  - Influence of calcitonin gene-related peptide on histamine- and substance P
      induced itch, flare and weal in humans.
AB  - Recent data have shown both synergistic and inhibitory effects between calcitonin
      gene-related peptide (CGRP) and substance P (SP) on inflammation and flare
      responses. The modulatory effects of CGRP on the itch, flare and weal responses
      following intracutaneous injections of SP and histamine were studied in 10
      healthy volunteers. The only change in itch responsiveness observed was a
      significant prolongation of itch latency following SP when preceded 10 min
      earlier by a CGRP injection. No influence on flare and weal was observed.

PMID- 7506046
TI  - Leukemia inhibitory factor mediates an injury response but not a target-directed
      developmental transmitter switch in sympathetic neurons.
AB  - Leukemia inhibitory factor (LIF; also known as cholinergic differentiation
      factor) is a multifunctional cytokine that affects neurons, as well as many other
      cell types. To examine its neuronal functions in vivo, we have used LIF-deficient
      mice. In culture, LIF alters the transmitter phenotype of sympathetic neurons,
      inducing cholinergic function, reducing noradrenergic function, and altering
      neuropeptide expression. In vivo, a noradrenergic to cholinergic switch occurs in
      the developing sweat gland innervation, and changes in neuropeptide phenotype
      occur in axotomized adult ganglia. We find that the gland innervation of LIF
      deficient mice is indistinguishable from normal. In contrast, neuropeptide
      induction in ganglia cultured as explants or axotomized in situ is significantly
      suppressed in LIF-deficient mice. Thus, LIF plays a role in transmitter changes
      induced by axotomy but not by developmental interactions with sweat glands.

PMID- 7506048
TI  - Phosphotyrosine-containing proteins are concentrated in differentiating cells
      during chicken embryonic development.
AB  - Protein tyrosine phosphorylation may be an important indicator of both the
      proliferative status and differentiation status of cells during embryonic
      development. To determine how each of these factors contributes to the level of
      phosphotyrosine-containing proteins detectable in embryonic tissues we have used
      immunohistochemistry with anti-phosphotyrosine antibodies on sections of
      developing chicken embryos. In contrast to an earlier study (Takata and Singer,
      1988) we found proteins phosphorylated on tyrosine residues to be present in many
      different cells of the developing chicken embryo. The successful detection of
      phosphotyrosine-containing proteins in many cell types required the presence of
      sodium orthovanadate, a phosphotyrosine phosphatase inhibitor, during fixation.
      Despite the fact that the majority of tyrosine kinases identified to date are
      growth factor receptors, the highest levels of phosphotyrosine-containing
      proteins in many tissues were localized to populations of cells which were
      differentiating or migrating rather than dividing.

PMID- 7506050
TI  - Pre-clinical palliative medicine education at the Medical College of Wisconsin.
AB  - A newly designed six-week course, Palliative Medicine, for second-year medical
      students at the Medical College of Wisconsin is described. A previous course on
      death and dying received unfavorable student reviews related to an emphasis on
      philosophical and theoretical concepts concerning death. The new course presented
      the concepts of palliative medicine in the context of practical clinical care
      issues and physician-patient-family communication issues. Student evaluations
      were very favorable. Implications for legitimizing palliative care in the United
      States are discussed.

PMID- 7506049
TI  - Effect of acute magnesium deficiency on the masking and unmasking of the proton
      channel of the uncoupling protein in rat brown fat.
AB  - The short term regulation of heat production in brown adipose tissue mitochondria
      (BAT) of acutely Mg-deficient rats was demonstrated by comparing several
      parameters of mitochondrial energization. Mg deficiency in vivo had absolutely no
      effect on the BAT uncoupling protein concentration (UCP) which was only modified
      by thermal conditions. The same high concentration was observed 10 d cold exposed
      control and Mg-deficient rats. Four days of warm re-exposure at thermal
      neutrality led to a moderate 26 per cent decrease with both diets which was not
      modified by cold stress for 1 h. Proton conductance. CmH+, and proton motive
      force, delta p, were calculated from membrane potential and respiration rate
      measurements. The same high level CmH+ was observed in cold exposed rats with
      both diets. Compared to warm re-exposed control rats, CmH+ was threefold higher
      in the corresponding Mg-deficient group which indicated a much lower masking of
      the proton channel of UCP with the Mg-deficient diet. This difference was not
      dependent on the presence of magnesium in vitro. The basal CmH+, independent of
      UCP, was not altered by magnesium deficiency. These results emphasize that acute
      regulation of thermogenic BAT activity through the masking and unmasking process
      is altered when magnesium supply is limited in vivo.

PMID- 7506051
TI  - The Canadian Palliative Care Undergraduate Curriculum.
AB  - In 1988 the deans of 12 (out of 16) Canadian medical schools appointed
      representatives to a Canadian Palliative Care Curriculum Committee. The Committee
      has subsequently published the Canadian Palliative Care Curriculum which outlines
      specific goals and objectives for palliative care instruction in undergraduate
      medical teaching. The Curriculum covers 22 different topics, including 13
      symptoms and 9 psychosocial issues. The Canadian Curriculum Committee continues
      to meet and is now considering other national educational initiatives in
      palliative care.

PMID- 7506052
TI  - Purification and characterization of prolyl endopeptidase from rat skin.
AB  - An enzyme with the specificity of a prolyl endopeptidase was purified
      approximately 329-fold from rat skin. The enzyme has a molecular weight of 70,000
      as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a
      pH optimum of 5.8 as checked with 7-(Succinyl-Gly-Pro)-4- methylcoumarinamide
      (Suc-Gly-Pro-MCA) as the substrate. The optimal temperature for the enzyme
      activity was 40 degrees C. The Km and Vmax values for Suc-Gly-Pro-MCA were 0.7 mM
      and 68 nmol/min per mg protein, respectively. The enzyme activity was markedly
      inhibited by diisopropyl fluorophosphate, p-chloromercuribenzoic acid, N
      ethylmaleimide, Zn2+ and Cu2+, while it was partially inhibited by
      phenylmethanesulphonyl fluoride. The purified enzyme was shown to release the N
      terminal tetrapeptide, Arg-Pro-Lys-Pro, from substance P producing the C-terminal
      heptapeptide, Gln-Gln-Phe-Phe-Gly-Met- CONH2. In the skin, this enzyme might be
      related to the inactivation of substance P.

PMID- 7506053
TI  - Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of
      oxidized LDL.
AB  - Atherosclerotic lesions contain relatively large quantities of IgG. We have
      previously shown that both human and rabbit sera contain autoantibodies against
      epitopes of oxidized (Ox) low-density lipoprotein (LDL) and that LDL isolated
      from atherosclerotic lesions contains small amounts of tightly bound IgG.
      However, it is not known whether IgG isolated from atherosclerotic lesions
      recognizes epitopes present in native LDL or Ox-LDL. IgG was isolated from
      Watanabe heritable hyperlipidemic (WHHL) rabbit atherosclerotic lesions by
      sequential salt extractions, purified by fast protein liquid chromatography on
      protein G, and used in a solid-phase radioimmunoassay. IgG and immune complexes
      were also isolated from the saline extracts of human lesions by adsorption onto
      latex beads coated with anti-human IgG antibodies or protein A. IgG isolated from
      rabbit lesions showed significant titers against malondialdehyde (MDA)-modified
      LDL and LDL oxidized by copper ions for 4 and 18 hours but not against native
      LDL. On Western blots, lesion IgG stained MDA-LDL and fragments of Ox-LDL.
      Western blots of immune complexes isolated from human lesions revealed the
      presence in the isolated complexes of both apoprotein B and apoprotein B
      fragments, which reacted with antibodies to MDA-lysine. Furthermore, rabbit
      lesion IgG immunostained epitopes of Ox-LDL present in human atherosclerotic
      lesions. Immunostains obtained with rabbit lesion IgG were similar to those
      obtained with a monoclonal antibody specific for MDA-lysine. The results show
      that human and rabbit atherosclerotic lesions contain IgG that recognizes
      epitopes characteristic of Ox-LDL. These data suggest that immunologic processes
      may be an important component of the atherogenic process.

PMID- 7506056
TI  - Direct observation of differential UV photolytic degradation among the tryptophan
      residues of gramicidin A in sodium dodecyl sulfate micelles.
AB  - Gramicidin A, incorporated into sodium dodecyl sulfate micelles, was exposed to
      ultraviolet light and discovered by two-dimensional (TOCSY) NMR spectroscopy to
      undergo differential photolytic degradation. The four tryptophan residues of
      gramicidin A were found to be unequally sensitive to ultraviolet radiation.
      Tryptophan 9 was the most sensitive to ultraviolet photolysis, while tryptophan
      11 was the least sensitive. Tryptophans 13 and 15 have approximately the same
      susceptibility to photolytic degradation by the ultraviolet light. Rate constants
      for the photolytic degradation of the four tryptophan residues were obtained from
      the dependence of the TOCSY spectrum upon the time of photolysis.

PMID- 7506054
TI  - Epinephrine sensitizes human platelets in vivo and in vitro as studied by
      fibrinogen binding and P-selectin expression.
AB  - Epinephrine (Epi) infusion influences platelet activation markers in vivo, but in
      vitro studies have mainly examined supraphysiological Epi concentrations and have
      yielded conflicting results. In this study whole-blood flow-cytometric
      measurements of platelet fibrinogen binding and P-selectin expression were used
      to compare enhancement of ADP (0.1 to 10 mumol/L)-induced platelet activation by
      Epi infusion in vivo (0.1 and 0.4 nmol.kg-1.min-1) and by Epi in vitro (10 and 50
      nmol/L) in nine healthy volunteers. ADP caused concentration-dependent increases
      in the percentage of platelets that bound fibrinogen (from 4.4 +/- 0.9% to 69.9
      +/- 4.2%) and that expressed P-selectin (from 4.5 +/- 0.5% to 44.2 +/- 3.8%).
      Fibrinogen and P-selectin binding indices (FgBI and PSBI; calculated from mean
      fluorescence intensity and percentage of positive cells) also increased from 0.18
      +/- 0.03 to 11.70 +/- 1.99 for FgBI and from 0.22 +/- 0.03 to 2.34 +/- 0.29 for
      PSBI. Epi concentration-dependently enhanced fibrinogen binding and P-selectin
      expression in vitro (by approximately 30% at the midportion of the ADP curve at
      10 nmol/L Epi; P < .001 for both by ANOVAs). High-dose Epi infusion enhanced FgBI
      similarly and increased maximal P-selectin expression by 38%. Epi (50 nmol/L in
      vitro) enhanced platelet activation further, whether samples were taken with or
      without prior Epi infusion. Total expression of glycoprotein IIb/IIIa was
      unaffected by Epi infusion, but glycoprotein Ib expression per platelet was
      reduced (P < .05). These in vivo and in vitro effects of Epi on platelet
      responses to agonist stimulation indicate a prothrombotic potential for
      sympathoadrenal activation in humans.

PMID- 7506055
TI  - Partitioning of gramicidin A' between coexisting fluid and gel phospholipid
      phases.
AB  - The partitioning behavior of gramicidin A' was investigated in four binary
      phospholipid mixtures with coexisting fluid and gel phases. The ratio of the
      equilibrium peptide concentration in the fluid phase to that in the gel phase
      (i.e., the partition coefficient, Kp) was determined by analysis of the quenching
      of gramicidin A' tryptophanyl fluorescence by a spin-labeled phosphatidylcholine.
      The partition coefficient was used as a measure of the relative solubility of
      gramicidin A' in the four types of gel phases analyzed. The composition of the
      gel phase was entirely Ca(dioleoylphosphatidylserine)2 (Ca(di18:1-PS)2), or was
      rich in either distearoylphosphatidylcholine (di18:0-PC),
      dipalmitoylphosphatidylcholine (di16:0-PC), or dimyristoylphosphatidylcholine
      (di14:0-PC). Except in the last case, the gel phase was depleted of gramicidin
      A': Kp approximately 30 when the gel phase was Ca(di18:1-PS)2 or di18:0-PC-rich,
      Kp approximately 10 when the gel phase was di16:0-PC-rich, and Kp approximately 1
      when the gel phase was di14:0-PC-rich. The hydrophobic mismatch between the
      length of gramicidin A' and the length of the phospholipid acyl chains in the
      bulk gel phase is greatest with di18:1-PS and di18:0-PC, intermediate with di16:0
      PC, and least with di14:0-PC. The Kp measurements presented here are consistent
      with increasing solubility of gramicidin A' in the gel phase with decreasing
      hydrophobic mismatch.

PMID- 7506057
TI  - Ion velocity distributions in gramicidin channels determined with laser Doppler
      velocimetry.
AB  - Laser Doppler scattering from Tl(I) ions moving synchronously through an ensemble
      of gramicidin channels in a bilayer membrane gives their intrachannel velocity
      distribution. The observed velocity distributions are unimodal indicating that
      ion flow through some region or regions of the channels is relatively steady.
      Average intrachannel velocities range from 3.75 x 10(-2) m/s to 2.38 x 10(-1) m/s
      for transmembrane potentials between 10 mV and 150 mV, respectively.

PMID- 7506058
TI  - Photoaffinity behavior of a conjugate of oligonucleoside methylphosphonate,
      rhodamine, and psoralen in the presence of complementary oligonucleotides.
AB  - A 3'-[[2-[N-(3-aminopropyl)-N-(2-
      hydroxyethyl)amino]ethylphosphoryl]oligodeoxyribonucleoside methylphosphonate 12
      mer was synthesized using the Aha-CPG solid support [Thaden, J. and Miller, P.S.
      (1993) Bioconjugate Chem, companion paper in this issue]. The oligomer was
      conjugated at the 3' primary aliphatic amine with tetramethylrhodamine 5
      isothiocyanate. The rhodamine linker/spacer was stable in 10% fetal calf serum.
      After enzymatic phosphorylation, the molecule was conjugated at the 5' phosphate
      with 4'-[N-(2-aminoethyl)aminomethyl]-4,5',8- trimethylpsoralen [(ae(AMT)]. The
      rhodamine/psoralen doubly-conjugated oligomer formed photoadducts with
      complementary single-stranded DNA and RNA oligonucleotides when irradiated with
      long-wavelength ultraviolet light. The efficiency of UV cross-linking slightly
      exceeded that of a colinear, psoralen-derivatized oligonucleoside
      methylphosphonate, and exhibited relationships with UV fluence and temperature
      that are characteristic for psoralen-conjugated methylphosphonates. The 1:1
      complex formed with the oligodeoxyribonucleotide target could be detected by its
      red fluorescence. Mouse L949 cells grown in the presence of the double conjugate
      were shown by means of computer-assisted epifluorescence microscopy to have
      internalized it. There was an accumulation of intensely fluorescent points and
      spots in a juxtanuclear region of the cytoplasm, and a faint, diffuse signal in
      the entire cell area.

PMID- 7506060
TI  - Stimulation by insulin of protein synthesis in cultured chick embryo fibroblasts.
AB  - Insulin stimulates protein synthesis in skeletal muscle of young animals and has
      been reported to exert similar effects on a variety of mammalian cell types in
      culture. However, with chick embryo fibroblasts we found that the extent of this
      effect was very sensitive to the culture conditions of the cells prior to the
      insulin treatment. The most reproducible results were obtained with cells that
      had been sub-cultured into medium in which fetal calf serum was replaced with 2%
      horse serum. Insulin only stimulated protein synthesis when added at supra
      physiological concentrations. Insulin-like growth factor 1 was effective at much
      lower concentrations. Since chick embryo fibroblasts can be obtained in good
      yield, they offer, if treated under appropriate conditions, a suitable system for
      study of the mechanisms by which insulin and IGF-1 promote the initiation of
      protein synthesis in eukaryotic cells.

PMID- 7506059
TI  - Synthesis of dextran derivatives with thiol-specific reactive groups for the
      preparation of dextran-protein conjugates.
AB  - A novel strategy is described for the preparation of dextran-protein conjugates
      containing disulfide linkages. "Dormant" protected thiol groups are introduced as
      side chains on dextran. These can, in a later stage, be converted into thiol
      specific reactive disulfides by reaction with (alkoxycarbonyl)sulfenyl chloride.
      A dextran-protein conjugate is then easily formed by reaction with a thiol group
      of a cysteine side chain. The disulfide linkage between dextran and the model
      tripeptides reduced glutathione and N-Ac-L-Cys-L-Ala-L-Lys remains intact, even
      after 24 h of incubation at 37 degrees C in blood.

PMID- 7506061
TI  - Perspectives on the use of cytokines in the management of infectious
      complications of cancer.
AB  - Treatment of neoplastic diseases is followed by a variety of infectious
      complications. Neutropenia and functional defects of phagocytes are common
      consequences of cancer and its treatment and contribute to an increased
      susceptibility to infections. Cytokines with hematopoietic growth stimulatory
      and/or immunoenhancing properties, such as granulocyte-macrophage colony
      stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF),
      interleukin-3, interferon-gamma, macrophage colony-stimulating factor,
      interleukin-1, and interleukin-6 have been shown to either have clinical utility
      in patients with cancer and neutropenia or offer the promise to do so. GM-CSF and
      G-CSF, for example, have been shown to reduce the incidence of fever and
      infectious complications in patients with cancer and neutropenia. The role of
      cytokines for the treatment of defined infections (e.g., invasive mycoses) is
      under investigation.

PMID- 7506062
TI  - Focal and regional variations in the composition of the glycocalyx of large
      vessel endothelium.
AB  - The glycocalyx of the endothelium of the systemic arteries and vena cava of the
      rabbit was visualised by in situ perfusion fixation with glutaraldehyde
      containing Alcian blue. The thickness of the layer ranged from 45 +/- 1 nm in the
      coronary artery to 81 +/- 2 nm in the carotid. The glycocalyx was 20 +/- 1.5 nm
      thicker on the downstream side of intercostal ostia than on the upstream side.
      Changes in the staining pattern with increasing concentrations of MgCl2 indicated
      that carboxyl groups made the major contribution to the surface charge, though
      sulphate groups were also present, particularly in the aortic arch and carotid
      artery. Segments of the thoracic aorta and carotid artery were also stained in
      vitro with fluorescence labelled wheat germ agglutinin, and fluorescence
      intensity in histological sections was quantified using a video microscope
      equipped with a microcomputer-based image analysis system. The fluorescence
      intensity in the carotid was 1.65 +/- 0.15 times that in the aorta. Pretreatment
      with neuraminidase reduced fluorescence intensity by 60 +/- 4% in the carotid and
      53 +/- 2% on the upstream side of intercostal ostia, but only by 37 +/- 3% on the
      downstream side. Chondroitinase and heparanase both reduced binding and when used
      together their effect was additive, reducing fluorescence by 27 +/- 3, 51 +/- 4,
      and 32 +/- 3% at the three sites, respectively. Though the interpretation of the
      lectin binding experiments is complicated by a number of factors, these results
      support previous reports that sialyl groups are abundant in the endothelial
      glycocalyx. Glycosaminoglycans are also present, however, in significant amounts.

PMID- 7506063
TI  - Multichannel recordings from membranes which contain gap junctions. II. Substates
      and conductance shifts.
AB  - Substates which can last up to several seconds are found in the 100-pS channel of
      the earthworm septum, a putative gap junction channel. The conductance of these
      substates is highly variable from preparation to preparation, and they are found
      at almost every fraction of the whole channel conductance. Another phenomenon
      seen in multichannel recordings is the "conductance shift": here the current
      passed by several open channels differs from an integral multiple of the current
      when only one channel is open. These shifts can be modelled by 1) a resistance in
      series with the channel or 2) long-lived substates. Each of these models fails in
      particular cases to explain either the magnitude or direction of the shifts. It
      is possible that both effects are simultaneously present.

PMID- 7506064
TI  - P-selectin mediates neutrophil rolling on histamine-stimulated endothelial cells.
AB  - In postcapillary venules, marginating neutrophils (PMNs) are often seen rolling
      along the vessel wall prior to stopping and emigrating. There is substantial
      evidence in vitro and in vivo that the adhesion receptors E- and L-selectin
      participate in this phenomenon on cytokine-stimulated endothelium, and recent
      evidence has shown that a closely related adhesion receptor, P-selectin, is
      capable of mediating neutrophil rolling on an artificial membrane. Here we
      demonstrate and characterize PMN rolling on monolayers of human umbilical vein
      endothelial cells (HUVECs) stimulated with histamine to induce surface expression
      of P-selectin. Peak association of PMNs with the HUVECs occurs 10 min after
      histamine stimulation, and at a postcapillary venular wall shear stress of 2.0
      dyn/cm2 the rolling velocity is 14 microns/s. Approximately 95% of the PMNs roll
      on the endothelial cells, 5% adhere firmly, and none migrate beneath the
      endothelial monolayer. Monoclonal antibody (MAb) G1, which binds P-selectin and
      blocks its adhesive function, completely prevents association of the PMNs with
      histamine-stimulated HUVEC, whereas the nonblocking anti-P-selectin MAb S12 does
      not. Treatment of PMNs with the anti-L-selectin MAb DREG56 reduces PMN adherence
      by approximately 50%. Anti-CD54 MAb R6.5 and anti-CD18 MAb R15.7 have little
      effect on the number of PMNs rolling on the HUVECs but completely prevent PMNs
      from stopping and significantly increase rolling velocity. Nonblocking control
      MAbs for R6.5 (CL203) and R15.7 (CL18/1D1) lack these effects. Rolling adhesion
      of PMNs on histamine-stimulated HUVECs therefore appears to be completely
      dependent on endothelial cell P-selectin, with a minor adhesion-stabilizing
      contribution from intercellular adhesion molecule 1 and beta 2 integrins. The
      partial inhibition of rolling with DREG56 suggests that L-selectin may also play
      a role in neutrophil interactions with histamine-stimulated endothelium. We
      further characterize these interactions by determining the effects of the various
      MAbs and wall shear stresses on adhesion patterns, rolling velocities, and
      distributions of rolling velocities.

PMID- 7506065
TI  - Preventing errors when estimating single channel properties from the analysis of
      current fluctuations.
AB  - The conductance, number, and mean open time of ion channels can be estimated from
      fluctuations in membrane current. To examine potential errors associated with
      fluctuation analysis, we simulated ensemble currents and estimated single channel
      properties. The number (N) and amplitude (i) of the underlying single channels
      were estimated using nonstationary fluctuation analysis, while mean open time was
      estimated using covariance and spectral analysis. Both excessive filtering and
      the analysis of segments of current that were too brief led to underestimates of
      i and overestimates of N. Setting the low-pass cut-off frequency of the filter to
      greater than five times the inverse of the effective mean channel open time
      (burst duration) and analyzing segments of current that were at least 80 times
      the effective mean channel open time reduced the errors to < 2%. With excessive
      filtering, Butterworth filtering gave up to 10% less error in estimating i and N
      than Bessel filtering. Estimates of mean open time obtained from the time
      constant of decay of the covariance, tau obs, at low open probabilities (Po) were
      much less sensitive to filtering than estimates of i and N. Extrapolating plots
      of tau obs versus mean current to the ordinate provided a method to estimate mean
      open time from data obtained at higher Po, where tau obs no longer represents
      mean open time. Bessel filtering gave the least error when estimating tau obs
      from the decay of the covariance function, and Butterworth filtering gave the
      least error when estimating tau obs from spectral density functions.

PMID- 7506066
TI  - Potential, pH, and arachidonate gate hydrogen ion currents in human neutrophils.
AB  - Indirect evidence indicates that a proton-selective conductance is activated
      during the respiratory burst in neutrophils. A voltage- and time-dependent H(+)
      selective conductance, gH, in human neutrophils is demonstrated here directly by
      the whole-cell patch-clamp technique. The gH is extremely low at large negative
      potentials, increases slowly upon membrane depolarization, and does not
      inactivate. It is enhanced at high external pH or low internal pH and is
      inhibited by Cd2+ and Zn2+. Arachidonic acid, which plays a pivotal role in
      inflammatory reactions, amplifies the gH. The properties of the gH described here
      are compatible with its activation during the respiratory burst in stimulated
      neutrophils, in which it may facilitate sustained superoxide anion release by
      dissipating metabolically generated acid.

PMID- 7506067
TI  - Mechanisms of beta-adrenergic stimulation of cardiac Ca2+ channels revealed by
      discrete-time Markov analysis of slow gating.
AB  - Individual cardiac Ca2+ channels cycle slowly between a mode of gating in which
      the channel is available to open, and one in which the channel remains silent.
      The regulation of this multisecond cycling process by isoproterenol was
      investigated by single-channel recording and the development of a discrete-time
      Markov model that describes the slow switching among modes in terms of (de)
      phosphorylation reactions. The results provide evidence that isoproterenol
      increases Ca2+ channel activity by a reciprocal regulatory mechanism: not only is
      the phosphorylation rate of the channel increased, but also the dephosphorylation
      rate decreased. The discrete-time Markov formalism should prove useful as a
      general tool for understanding the mode switching demonstrated by a number of
      ionic channels.

PMID- 7506068
TI  - Mechanism of charybdotoxin block of a voltage-gated K+ channel.
AB  - Charybdotoxin block of a Shaker K+ channel was studied in Xenopus oocyte
      macropatches. Toxin on rate increases linearly with toxin concentration in an
      ionic strength-dependent fashion and is competitively diminished by
      tetraethylammonium. On rate is insensitive to transmembrane voltage and to K+ on
      the opposite side of the membrane. Conversely, toxin off rate is insensitive to
      toxin concentration, ionic strength, and added tetraethylammonium but is enhanced
      by membrane depolarization or K+ (or Na+) in the trans solution. Charge
      neutralization of charybdotoxin Lys27, however, renders off rate voltage
      insensitive. Our results argue that block of voltage-gated K+ channels results
      from the binding of one toxin molecule, so that Lys27 enters the pore and
      interacts with K+ (or Na+) in the ion conduction pathway.

PMID- 7506069
TI  - The use of quartz patch pipettes for low noise single channel recording.
AB  - Quartz has a dissipation factor of approximately 10(-4), which is an order of
      magnitude less than that of the best glasses previously used to fabricate patch
      pipettes; it's dielectric constant of 3.8 is also lower than that of other
      glasses. On the basis of these electrical characteristics it is expected that
      patch pipettes pulled from quartz tubing will produce significantly less noise
      than pipettes made from other glasses. Our work confirms these expectations and
      we describe theoretical and practical aspects of the use of quartz pipettes for
      single channel patch voltage clamp measurements. Methods for pulling quartz
      pipettes with a laser-based puller and coating them with low-loss elastomers are
      discussed, as are precautions that are necessary to achieve low noise recordings.
      We have shown that quartz pipettes can be pulled from tubing with outer diameter
      to inner diameter ratios as large as 3 and a method of applying heavy elastomer
      coatings all the way to the tip of pipettes is presented. Noise sources arising
      from the pipette and its holder are described theoretically, and it is shown that
      measured noise is in good agreement with such predictions. With low noise
      capacitive feedback electronics, small geometry holders, and thick-walled quartz
      pipettes coated with low-loss elastomers we have been routinely able to achieve
      noise of 100 fA rms or less in a 5-kHz bandwidth with real cell patches and a
      pipette immersion depth of approximately 2 mm. On occasion we have achieved noise
      as low as 60 fA rms in this bandwidth.

PMID- 7506070
TI  - [The effect of galanin on the experimental parkinsonian syndrome in rats induced
      by the intrastriatal administration of kainic acid].
AB  - Experiments in rats showed that intrastriatal administration of kainic acid in a
      dose of 100 but not 20 ng per side resulted in the development of behavioral
      disorders reminding those of Parkinsonian syndrome: bradykinesia, increased
      muscle rigidity, ptosis. Intrastriatal administration of galanin in doses of 10
      and 50 ng induced only a decrease of locomotor activity in the "open field". When
      co-administered with kainic acid (20 ng), galanin displayed a dose-dependent
      potentiation of behavioral Parkinsonian-like disturbances the severity of which
      increased depending on the dose used. It is concluded that galanin potentiates
      the kainic acid-induced development of the generator of pathologically enhanced
      excitation in the striatum underlying the mechanisms of Parkinsonian syndrome.
      Thus, the increased galaninergic striatal activity could participate in the
      mechanisms of the above-mentioned CNS disorders.

PMID- 7506071
TI  - [The mechanism of the anti-arrhythmia action of opioid receptor agonists and
      antagonists].
AB  - Enkephalins were injected intravenously at a dose of 0.1 mg/kg 15 minutes or 6
      hours before adrenalin or CaCl2 injection. Enkephalins were reported to prevent
      adrenal ventricular extrasystoles but not to influence CaCl2-induced
      dysrhythmias. Maximum antiarrhythmic effect of enkephalins was demonstrated 6
      hours later after the intravenous injection. Naloxone at a dose of 2 mg/kg and
      morphine at a dose of 1.5 mg/kg prevent adrenal arrhythmias 15 min and 6 hours
      later after injection. We believe that peripheral delta opiate receptors
      activation by enkephalins as well as the blockade of non-identified opiate
      receptors by naloxone prevent arrhythmias.

PMID- 7506072
TI  - [The anti-arrhythmia effect of Rhodiola rosea and its possible mechanism].
AB  - A course injection of Rhodiola rosea extract for eight days was reported to
      increase the resistance of experimental animals to adrenalin- or CaCl2-induced
      arrhythmias. Preliminary injection of naloxone in a dose of 0.5 mg/kg eliminated
      the antiarrhythmic effect of Rhodiola. Indomethacin had no effect the
      antiarrhythmic action of Rhodiola. The antiarrhythmic effect of Rhodiola course
      injections was assumed to be associated with the induction of opioid peptides
      biosynthesis.

PMID- 7506073
TI  - [The content of dynorphin, Met-enk-Arg6-Phe7 and substance P (1-11) in the brain
      of mice with different levels of ethanol consumption].
AB  - The dynorphin A (1-17), Met-enkephalin-Arg6-Phe7 and substance P levels were
      determined by RIA following Sep-Pak separation in the striatum, hippocampus and
      spinal cord of three strains of mice (C57Bl10/D1, A/Sn, A. CA). The C57Bl10/D1
      mice had high consumption of 10% ethanol at free choice schedule, whereas the
      A/Sn and A. CA mice had very low one. The Met-enkephalin-Arg6-Phe7 level was
      found to be decreased only in the spinal cord and striatum of C57Bl10/D1 mice. It
      is suggested that decreased synthesis or processing of the proenkephalin may at
      least partly determine the high level of ethanol consumption by this strain of
      mice.

PMID- 7506074
TI  - Experimental study of the effect of IH764-3 on pulmonary fibrosis.
AB  - IH764-3 is a potent component isolated from Salvia miltiorrhiza. We have studied
      the effect of IH764-3 on experimental pulmonary fibrosis in rats and mice treated
      with a single intratracheal instillation of bleomycin-A6. Three groups of animals
      were assigned as BLM+saline, BLM+IH764-3 and normal control. The results
      indicated that in the treated group, lung coefficient, surfactant, hydroxyproline
      content and FGF activity were significantly lower than those in the control group
      (P < 0.05, 0.05, 0.001 and 0.05, respectively). Electron microscopic examination
      showed that pulmonary ultrastructure was markedly better in the treated group:
      type II alveolar epithelial cells, infiltrating inflammatory cells, proliferating
      collagen-forming cells, collagen and elastic fibers were obviously fewer in the
      treated group. These results demonstrate that IH764-3 has prophylactic and
      therapeutic effects on pulmonary fibrosis.

PMID- 7506075
TI  - Amplification of Sca-1+ Lin- WGA+ cells in serum-free cultures containing steel
      factor, interleukin-6, and erythropoietin with maintenance of cells with long
      term in vivo reconstituting potential.
AB  - Normal murine bone marrow (BM) cells were sorted on the basis of low forward and
      orthogonal light scatter properties, Sca-1 expression (Sca-1+), lack of staining
      with a cocktail of mature hematopoietic lineage markers (Lin-), and binding of
      wheat germ agglutinin (WGA+). This approach allowed the reproducible isolation of
      a very small subpopulation (0.037% +/- 0.023% of all nucleated BM cells) that was
      approximately 400-fold enriched in cells capable of reconstituting both lymphoid
      and myeloid lineages in lethally irradiated recipients. Transplantation of 30 or
      10 of these Sca-1+Lin-WGA+ cells resulted in > or = to 20% donor-derived
      nucleated peripheral blood cells 3 months posttransplantation in 100% and 22% of
      the recipients, respectively. When Sca-1+Lin-WGA+ cells were cultured in serum
      free medium supplemented with Steel factor, interleukin-6 (IL-6), and
      erythropoietin (with or without IL-3), a large increase in total cell number,
      including cells with an Sca-1+Lin-WGA+ phenotype was observed. Single cell
      cultures showed that 90% to 95% of the input cells underwent at least one
      division during the first 2 weeks and the remainder died. Interestingly, this
      proliferative response was not accompanied by a parallel increase in the number
      of cells with both lymphoid and myeloid repopulating potential in vivo, as
      quantitation of these by limiting dilution analysis showed they had decreased
      slightly (1.3-fold) but not significantly below the number initially present.
      These results demonstrate that Sca-1+Lin-WGA+ cells with long-term repopulating
      potential can be maintained for 2 weeks in a serum- and stroma cell-free culture,
      providing a simple in vitro system to study their behavior under well-defined
      conditions. The observed expansion of Sca-1+Lin-WGA+ cells in vitro without a
      concomitant increase in reconstituting cells also shows that extensive functional
      heterogeneity exists within populations of cells with this surface phenotype.

PMID- 7506076
TI  - Ligand-dependent polyubiquitination of c-kit gene product: a possible mechanism
      of receptor down modulation in M07e cells.
AB  - Quantities of proteins in cells are balanced by protein synthesis and
      degradation. Protein ubiquitination is an important adenosine-triphosphate
      dependent proteolytic pathway for "short-lived" proteins. We show that soluble
      steel-factor (SLF) stimulation at 37 degrees C rapidly induced polyubiquitination
      of c-kit protein in growth-factor-dependent human-myeloid cell line M07e,
      resulting in smeared, retarded migration of c-kit protein in sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis in the molecular weight region of 145
      kD. Receptor ubiquitination was almost completely absent when cells were treated
      with SLF at 4 degrees C or at 37 degrees C in the presence of 0.2% sodium azide,
      or when the cells were pretreated with anti-c-kit monoclonal antibody or
      genistein, a tyrosine-kinase inhibitor. This suggested that c-kit ubiquitination
      was ligand dependent and appeared to require intrinsic tyrosine-kinase activation
      of the c-kit protein. Flow-cytometric analysis of c-kit expression on the cell
      surface of M07e cells showed down modulation of c-kit within 5 minutes after
      soluble-SLF treatment at 37 degrees C. However, rapid receptor down modulation
      was almost completely suppressed when cells were treated with SLF at 4 degrees C
      or at 37 degrees C in the presence of 0.2% sodium azide, conditions that
      concomitantly suppressed polyubiquitination of c-kit protein. In addition, these
      conditions almost completely suppressed radiolabeled SLF (125I-SLF)
      internalization after ligand-receptor interaction. Pulse-chase studies of 35S
      methionine-labeled c-kit protein showed that SLF stimulation at 37 degrees C
      strikingly enhanced c-kit degradation (T1/2; approximately 20 minutes) compared
      with that in cells stimulated with SLF at 4 degrees C or at 37 degrees C with
      0.2% sodium azide. However, in the presence of chloroquine, which blocks
      lysosomal degradation, this ligand-induced c-kit degradation at 37 degrees C was
      only suppressed in part. These data suggest that SLF-induced polyubiquitination
      of the c-kit receptor protein may play a role in regulation of c-kit-encoded
      protein-receptor expression in M07e cells.

PMID- 7506077
TI  - Aged platelets have an impaired response to thrombin as quantitated by P-selectin
      expression.
AB  - After the intravenous infusion of N-hydroxysuccinimido biotin into dogs, 80.6% +/
      9.7% (n = 5) of platelets were covalently labeled with biotin. The in vivo
      survival of the biotinylated platelets was monitored by flow cytometry and was
      normal as compared with previous reports for dog platelets. The ability of the
      biotinylated platelets to be activated was analyzed by measuring the expression
      of cell-surface P-selectin after incubation with graded concentrations of
      thrombin. When P-selectin expression was examined 3 hours after labeling,
      biotinylated platelets were indistinguishable from the nonlabeled population of
      platelets, indicating that biotinylation did not adversely affect the cells. On
      consecutive days after biotinylation, the thrombin dose-response curves for
      biotinylated and nonbiotinylated platelets were repeated, and as the biotinylated
      platelets aged, they became less responsive to thrombin. On days 3, 4, and 5, the
      thrombin EC50 for the aged, biotinylated platelets as compared with the total
      population of platelets was 136%, 150%, and 178%, respectively. Increasing age
      clearly impairs the reactivity of platelets towards thrombin as quantitated by
      the expression of cell-surface P-selectin.

PMID- 7506078
TI  - In vitro exposure to human immunodeficiency virus type 1 induces apoptotic cell
      death of the factor-dependent TF-1 hematopoietic cell line.
AB  - In this study, we evaluated the effect of a short-term exposure (2 hours) to two
      different lymphocytotropic strains of human immunodeficiency virus type 1 (HIV-1;
      HIVIIIB and ICR-3) on the survival of a factor-dependent CD34+ hematopoietic
      progenitor cell line (TF-1). At flow cytometry analysis, a significant (P < .05)
      increase in the frequency of apoptotic cell death was observed in HIV-1-treated
      TF-1 cells, supplemented with low doses of either interleukin-3 (IL-3; 0.02 to 1
      ng/mL) or granulocyte-macrophage colony-stimulating factor (GM-CSF; 0.02 to 0.2
      ng/mL) with respect to mock-treated cells. On the other hand, higher doses of
      both cytokines or combinations of suboptimal concentrations of IL-3 plus GM-CSF
      (eg, 0.2, plus 0.2 ng/mL) completely reversed the HIV-1-induced increase of
      apoptosis. Remarkably, no signs of productive or latent virus replication were
      ever observed in HIV-1-treated TF-1 cells up to 16 days of liquid culture. In
      parallel experiments, the in vitro exposure to HIVIIIB induced a significant and
      progressive increase of apoptotic death in purified bone marrow CD34+ cells,
      seeded in liquid cultures in the presence of 1 ng/mL IL-3. The HIV-1-induced
      apoptosis of TF-1 cells was likely triggered by the simple interaction of HIV-1
      envelope glycoprotein gp120 with CD4 receptor, which was expressed at a low level
      on the surface of TF-1 cells. In fact, treatment of TF-1 cells with recombinant
      gp120 plus a polyclonal anti-gp120 antibody or with anti-CD4 monoclonal antibody
      plus rabbit antimouse IgG significantly increased the percentage of apoptotic
      death. These data suggest that HIV-1, and perhaps also free gp120 in the presence
      of anti-gp120 antibody; could play a direct role in the pathogenesis of
      peripheral blood cytopenias in acquired immunodeficiency syndrome patients by
      inducing apoptotic death of hematopoietic progenitor cells without the need of a
      direct infection.

PMID- 7506079
TI  - Synergy between cyclosporin A and a monoclonal antibody to B7 in blocking
      alloantigen-induced T-cell activation.
AB  - Costimulatory signals are absolutely required for T-cell activation after T-cell
      receptor/major histocompatibility complex-peptide interaction. So far, the best
      known candidate essential costimulatory signal is mediated by interaction of CD28
      on T cells with B7 on antigen-presenting cells. Using an allogeneic B7+ Epstein
      Barr virus-transformed B-cell line as stimulator, we found that addition of a
      monoclonal antibody (MoAb) to B7 that efficiently blocks B7-CD28 interaction only
      partially inhibited proliferation and interleukin-2 (IL-2) production in primary
      and secondary mixed lymphocyte reactions (MLR), whereas the generation of
      cytotoxic T lymphocytes (CTL) was not affected. Inhibition of primary or
      secondary MLR-induced T-cell activation with cyclosporin A (CsA) at nontoxic
      concentrations also was never complete. However, the combination of CsA and anti
      B7 MoAb B7-24 synergistically blocked allogeneic B cell-induced T-cell
      proliferation, IL-2 production, and CTL generation. These data suggest that the
      mere blockage of B7-CD28 interaction during allotransplantation will be
      insufficient to prevent rejection or graft-versus-host disease. However, low CsA
      concentrations, when combined with an agent blocking B7-CD28 interaction, can
      potentially achieve complete immunosuppression.

PMID- 7506080
TI  - Murine myeloid cells transformed by myb require fibroblast-derived or autocrine
      growth factors in addition to granulocyte-macrophage colony-stimulating factor
      for proliferation.
AB  - Murine myeloid cells can be transformed in vitro by infection with recombinant
      retroviruses carrying activated myb genes. While these myb-transformed
      hematopoietic cells (MTHCs) can proliferate continuously in culture, they exhibit
      several characteristics of progenitor cells of the granulocyte-macrophage (GM)
      lineage, including an absolute dependence on hematopoietic growth factors (HGFs)
      such as GM colony-stimulating factor (GM-CSF) for survival and growth. Whereas we
      have previously shown that MTHCs respond synergistically to certain combinations
      of HGFs, we report here that MTHCs apparently require two HGFs for proliferation,
      because GM-CSF alone appears insufficient to promote growth when MTHCs are
      cultured at very low densities. However, proliferation can be stimulated by
      either increasing the density at which MTHCs are cultured (implying the
      production of an autocrine growth factor) or by the presence of a feeder layer of
      irradiated fibroblasts. We find that the activity of such feeder layers is
      greatest when the MTHCs are allowed to contact them directly; and by using mutant
      fibroblast lines, that it depends on the production of CSF-1, but not Steel
      factor (SLF). In contrast, the autocrine factor appears not to be either CSF-1 or
      SLF, and the possibility is raised that it may represent a novel HGF activity.
      Potential implications of these results for normal and leukemic hematopoiesis are
      discussed.

PMID- 7506081
TI  - Aberrant regulation of complement by the erythrocytes of hereditary
      erythroblastic multinuclearity with a positive acidified serum lysis test
      (HEMPAS).
AB  - Susceptibility to hemolysis in acidified serum is a pathognomonic feature of
      hereditary erythroblastic multinuclearity with a positive acidified serum lysis
      test (HEMPAS, congenital dyserythropoietic anemia type II). The purpose of the
      studies reported herein was to determine if aberrant regulation of complement
      contributes to the susceptibility of HEMPAS erythrocytes to acidified serum
      lysis. The results of these experiments have demonstrated that regulation of both
      the C3 convertase of the alternative pathway and the membrane attack complex of
      complement by HEMPAS erythrocytes is aberrant. However, these abnormalities are
      not a consequence of quantitative or functional deficiencies of the erythrocyte
      complement-regulatory proteins, decay accelerating factor (DAF, CD55), or
      membrane inhibitor of reactive lysis (MIRL, CD59). Our recent studies have shown
      that glycophorin A (GPA), the major erythrocyte sialoglycoprotein is a complement
      regulatory protein. Analysis by radioimmunoprecipitation suggested that GPA on
      HEMPAS erythrocytes is abnormally glycosylated. Further analysis indicated that
      the abnormality involves the O-linked oligosaccharide moiety. Together, these
      studies show that complement regulation by HEMPAS erythrocytes is abnormal and
      that constituents other than DAF and MIRL participate in controlling complement
      activation on the erythrocyte membrane. Additionally, these studies suggest that
      the glycosylation defect that is characteristic of HEMPAS involves GPA.

PMID- 7506082
TI  - The acute-phase protein alpha 1-antitrypsin inhibits growth and proliferation of
      human early erythroid progenitor cells (burst-forming units-erythroid) and of
      human erythroleukemic cells (K562) in vitro by interfering with transferrin iron
      uptake.
AB  - We have previously shown that the hepatic acute-phase protein alpha 1-antitrypsin
      (alpha 1-AT) inhibits transferrin (tf) binding to its receptor (tfR) of human
      placental membranes. To evaluate the possibility that this interaction can
      explain the pathophysiology of the changes in iron metabolism in the course of
      chronic disease, subsequently leading to anemia in chronic disease (ACD), we
      examined the effect of alpha 1-AT on cells of the erythroid cell line. alpha 1-AT
      completely prevented tf binding to tfR on K562 human erythroleukemic cells and on
      reticulocytes. This inhibitory potency was dose-dependent and competitive, as
      proved in equilibrium saturation and kinetic studies. The cytokines interleukin-1
      (IL-1), IL-6, and tumor necrosis factor alpha showed no such effect.
      Internalization of the tf-tfR complex was inhibited with alpha 1-AT in a dose
      dependent manner. Furthermore, alpha 1-AT profoundly reduced the growth of K562
      cells as well as their proliferation, albeit to a lesser degree. Growth of early
      erythroid progenitor cells (burst-forming units-erythroid) was significantly
      suppressed by alpha 1-AT, but no effect on the growth of late erythroid
      progenitor cells (colony-forming units-erythroid) was detected. These inhibitions
      of alpha 1-AT were seen in high physiologic concentrations attained in the course
      of acute-phase situations. These data show that alpha 1-AT might be a mediator of
      the changes in iron metabolism that are characteristic of clinical findings in
      the course of ACD.

PMID- 7506083
TI  - Effects of stem cell factor (kit-ligand) and interleukin-3 on the growth and
      serine proteinase expression of rat bone-marrow-derived or serosal mast cells.
AB  - The effects of rat stem-cell factor (SCF) and interleukin-3 (IL-3), alone or in
      combination, on the in vitro growth and serine proteinase expression of rat
      serosal/connective-tissue mast cells (CTMC) or bone marrow-derived mast cells
      (BMMC) were examined. Rat SCF stimulated the growth of both CTMC and BMMC. IL-3
      stimulated BMMC growth to a lesser extent than did SCF, whereas CTMC numbers did
      not increase in IL-3. However, SCF and IL-3 had synergistic effects on the growth
      of both BMMC and CTMC. SCF favoured the maintenance of rat mast cell proteinase-I
      (RMCP-I) in CTMC, but did not induce detectable production of RMCP-I in BMMC. In
      contrast, when IL-3 or lymph node-conditioned medium (LNCM) was added to SCF, a
      subpopulation of CTMC expressed and stored the soluble proteinase RMCP-II. In
      BMMC, the RMCP-II content of cells maintained in SCF was significantly less than
      that of cells maintained in IL-3 or LNCM. RMCP-II also appeared in the
      supernatants of BMMC, especially when BMMC numbers were increasing rapidly in SCF
      with or without IL-3 or LNCM. Thus, SCF and IL-3 can regulate the growth of rat
      BMMC and CTMC, as well as influence their production and release of proteinases.

PMID- 7506084
TI  - Synergistic interaction between interleukin-12 and steel factor in support of
      proliferation of murine lymphohematopoietic progenitors in culture.
AB  - We have investigated the effects of interleukin (IL)-12 (natural killer cell
      stimulatory factor/cytotoxic lymphocyte maturation factor) on the proliferation
      of murine myeloid and lymphohematopoietic progenitors in methylcellulose culture.
      In the presence of erythropoietin (Ep), IL-12 alone failed to support colony
      formation by mononuclear and enriched marrow cells of normal mice. Steel factor
      (SF) alone supported primarily formation of granulocyte/macrophage (GM) colony
      formation. However, the combination of the two cytokines yielded a significant
      number of multilineage colonies. When tested on marrow cells from 5-fluorouracil
      (5-FU)-treated mice, the combination of IL-12 and SF, but not the single factors,
      was effective in support of formation of various types of colonies. Approximately
      25% of these colonies yielded pre-B-cell colonies when replated in secondary
      culture containing SF and IL-7, indicating that IL-12 can interact with SF in
      supporting the development of primitive lymphohematopoietic progenitors. These
      results demonstrate that IL-12, a cytokine believed to be involved in the
      development of cell-mediated immune responses, has a wider range of activity,
      including committed myeloid and multipotent lymphohematopoietic progenitors.

PMID- 7506085
TI  - Suprachiasmatic nucleus neurochemistry in the conscious brain: correlation with
      circadian activity rhythms.
AB  - The aim of the research reported here was to provide information on the
      neurochemical processes that underlie the generation and entrainment of mammalian
      circadian rhythms. The studies were centered principally around the in vivo brain
      microdialysis technique for assessing the daily pattern of neurotransmitter
      activity in the suprachiasmatic hypothalamus of freely behaving Syrian and
      Siberian hamsters. This approach yielded several findings related to the
      activities of serotonergic and excitatory amino acid systems in the region of the
      suprachiasmatic nuclei (SNC). Specifically, we found that (1) there were daily
      variations in the extracellular concentrations of 5-hydroxyindoleacetic acid (5
      HIAA) and glutamate (GLU) in the SCN region (highest levels of 5-HIAA occurred
      soon after lights-off, whereas GLU peaked later in the dark phase); (2) the daily
      rhythm of GLU, but not serotonin, in the SCN region appeared to be circadian in
      nature and was not driven by an external influence; (3) the rhythm in GLU
      measured in SCN microdialysate involved a tetrodotoxin-insensitive mechanism and
      did not appear to be directly linked to the expression of locomotor behavior; and
      (4) direct application of serotonin receptor agonists via the microdialysis probe
      suppressed the concentration of extracellular GLU in the SCN region, suggesting
      that serotonin may modulate GLU release in the SCN.

PMID- 7506086
TI  - The immunohistochemical effect of a hydrocolloid occlusive dressing (DuoDERM E)
      in psoriasis vulgaris.
AB  - The topical application of a hydrocolloid occlusive dressing (HCD) has been shown
      in various studies to have an antipsoriatic effect as monotherapy but especially
      in combination with a topical corticosteroid. The aim of the present study was to
      assess the effect of 3 weeks of HCD monotherapy at the immunohistochemical level.
      Ten patients were treated. Before and after treatment, a biopsy was taken, and
      immunohistochemical stainings were carried out with markers for epidermal growth,
      keratinization, inflammation and endothelium. Suprabasal expression of keratin
      16, the number of cycling epidermal cells and the number of polymorphonuclear
      leucocytes and T lymphocytes tended to decrease during treatment. The endothelial
      markers did not change during HCD treatment. This study confirms the
      antipsoriatic effect of HCD and demonstrates that its effect upon some markers of
      inflammation, epidermal proliferation and keratinization is modest.

PMID- 7506087
TI  - The retron: a bacterial retroelement required for the synthesis of msDNA.
AB  - 'Retrons' are bacterial retroelements responsible for the synthesis of msDNA, a
      hybrid nucleic acid consisting of a single-stranded DNA that is branched out from
      an internal guanosine of an RNA molecule via a 2',5'-phosphodiester linkage.
      Retrons are found in a minor population of various bacterial species and are
      extensively diverse. Two important questions now demanding attention are whether
      retrons are mobile elements and why are they so diverse?

PMID- 7506088
TI  - Phylogenetic affiliations of Rhodoferax fermentans and related species of
      phototrophic bacteria as determined by automated 16S rDNA sequencing.
AB  - 16S rDNA sequences of strains of Rhodoferax fermentans were analyzed and compared
      with those of species of the genera Rubrivivax and Rhodocyclus. Approximately 1.5
      kb fragments of 16S rDNA from crude cell lysates were amplified by the polymerase
      chain reaction (PCR) and sequenced directly by using Tth DNA polymerase with the
      linear PCR sequencing protocol, followed by on-line detection with an automated
      laser fluorescent DNA sequencer. Pairwise sequence comparisons and distance
      matrix tree analysis showed that Rhodoferax fermentans, Rubrivivax gelatinosus,
      and Rhodocyclus species belong to three separate lineages within the beta
      subclass of the Proteobacteria, thereby confirming the phylogenetic validity of
      the genus Rhodoferax, as well as of the genera Rubrivivax and Rhodocyclus.

PMID- 7506089
TI  - Down-regulation in the production of matrix metalloproteinase 1 by human aortic
      intimal smooth muscle cells.
AB  - Effects of dexamethasone, retinoic acid, prostaglandin E2 (PGE2), and Iloprost as
      a agonist of prostacyclin (A-PGI2) on DNA synthesis and production of a precursor
      of matrix metalloproteinase 1 (tissue procollagenase/proMMP-1) by human aortic
      smooth muscle cells were investigated. When after treatment with platelet-derived
      growth factor (PDGF), these agents were added to the cultures, DNA synthesis and
      production of proMMP-1 were inhibited in a dose-dependent manner. These results
      suggest that these agents are negative regulators of PDGF. Since these agents are
      present in the blood or produced in the blood wall, in addition, since PDGF plays
      the most important role in the process of atherosclerosis, we propose that these
      agents function in vivo as a systems of protection against atherosclerosis.

PMID- 7506090
TI  - Stimulation of globin synthesis by 11-amino acid peptide.
AB  - We have used synthetic peptide to study a conserved RNA binding motif in
      eukaryotic poly(A) binding protein (PABP) as well as its functions. We
      synthesized an 11 amino-acid peptide based on the consensus sequence (GKSKGFGFV),
      which is found in all the sequenced eukaryotic PABPs. The synthetic peptide was
      found to be preferentially bound to the poly(A) alone or the poly(A) attached to
      the 3'-end of mRNA and not the deadenylated mRNA. Additionally, the 11-mer had
      strong affinity to bind to ATP. In vitro translation of rabbit globin mRNA
      poly(A) in the presence of the 11-mer resulted in stimulation of globin synthesis
      by two-fold as compared to translation in the presence of either deadenylated
      globin mRNA or globin mRNA poly(A) but in the absence of the 11-mer.

PMID- 7506091
TI  - Phase I/II study of high-dose cyclophosphamide, etoposide and cisplatin followed
      by autologous bone marrow or peripheral blood stem cell transplantation in
      patients with poor prognosis Hodgkin's disease or non-Hodgkin's lymphoma.
AB  - We conducted a phase I/II study to determine the efficacy, toxicity and maximum
      tolerable doses of CY, etoposide and cisplatin (CEP) in the management of
      patients with relapsed or refractory malignant lymphoma. Thirty patients with
      relapsed or refractory Hodgkin's disease (n = 10) or non-Hodgkin's lymphoma (n =
      20) received CY 6000 mg/m2, etoposide 900-2700 mg/m2 and cisplatin 150 mg/m2
      followed by autologous BM or autologous peripheral blood stem cell rescue. The
      dose of etoposide was escalated after each 3 to 4 patients. The maximum tolerated
      dose of etoposide, when administered with the indicated doses of CY and
      cisplatin, was 2400 mg/m2. Three of the 30 patients (10%) died of treatment
      related toxicity. Although 14 of the 30 patients had residual bulky and/or
      chemotherapy-resistant disease at the time of the transplant, 26 patients (87%)
      responded to this regimen, including 18 patients (60%) who achieved CR and 8
      patients (27%) who achieved partial remission. Seven patients (23%) remain alive
      and free of progression at a median of 21 months post-transplant. Three
      additional patients relapsed after transplant but are enjoying prolonged disease
      free survival at a median of 31 months post-transplant following additional post
      transplant therapy. We conclude that high-dose CY, etoposide and cisplatin
      followed by autologous BM or peripheral blood stem cell rescue is an active and
      acceptably tolerated regimen in the treatment of relapsed or refractory malignant
      lymphoma.

PMID- 7506092
TI  - Treatment with rhG-CSF pre and post-autologous bone marrow transplantation in
      children.

PMID- 7506093
TI  - Humoral autoimmune response in Chagas' disease: Trypanosoma cruzi ribosomal
      antigens as immunizing agents.
AB  - Molecular expression cloning techniques have revealed that patients with chronic
      Chagas' heart disease (cChHD) present a strong humoral response against the
      cloned C-terminal portions of the four Trypanosoma cruzi ribosomal P proteins
      TcP1, TcP2 alpha (TcP2b), TcP2 beta (TcPJL5), and TcP0. This protein family
      presents several features that may be important in the immunopathology of Chagas
      disease. Their exposed location on the ribosome, and the amplification of their
      parasite-specific, Ser free C-terminal domain, generate a strong anti-parasite P
      response that may induce anti-P autoimmunity. Evidences indicate that the
      serological pattern of the anti-P response from chagasic patients may be the
      consequence of a chronic immunization with T. cruzi ribosomal antigens.

PMID- 7506094
TI  - Immunological studies of an artificial antigen with specificity of a common
      polysaccharide antigen of Pseudomonas aeruginosa.
AB  - Synthetic D-rhamnan, with the structure of Pseudomonas aeruginosa common
      polysaccharide antigen (CPA), was conjugated with BSA. The artificial antigen
      obtained, and the natural antigens, lipopolysaccharides (LPS) of P. aeruginosa
      and Pseudomonas cerasi with rhamnan chains of the same structure, were studied by
      ELISA with rabbit antibodies to the D-rhamnan-BSA conjugate and to the P. cerasi
      O-antigen. Immunological relations between the LPS of P. aeruginosa and P. cerasi
      determined by CPA as well as between these LPS and D-rhamnan-BSA were revealed by
      ELISA. O-antiserum to P. cerasi possesses protective activity in the mouse
      passive protection test when mice are challenged with some P. aeruginosa strains;
      the antiserum to the D-rhamnan-BSA does not possess protective activity in mice.

PMID- 7506095
TI  - De novo mutation of the myelin P0 gene in Dejerine-Sottas disease (hereditary
      motor and sensory neuropathy type III).
AB  - We have investigated the myelin P0 gene on chromosome 1 as a candidate gene in
      two sporadic cases with Dejerine-Sottas disease or hereditary motor and sensory
      neuropathy (HMSN) type III. We found different mutations, a cysteine substitution
      for serine 63 in the extracellular domain and an arginine substitution for
      glycine 167 in the transmembrane domain. The patients were genetically
      heterozygous for the normal allele and the mutant allele, which was absent in
      their parents and in one hundred unrelated, healthy controls. The results
      strongly suggest that a de novo dominant mutation of the P0 gene is responsible
      for at least some sporadic cases of Dejerine-Sottas disease.

PMID- 7506096
TI  - A mutation in CFTR produces different phenotypes depending on chromosomal
      background.
AB  - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance
      regulator (CFTR) gene but the association between mutation (genotype) and disease
      presentation (phenotype) is not straightforward. We have been investigating
      whether variants in the CFTR gene that alter splicing efficiency of exon 9 can
      affect the phenotype produced by a mutation. A missense mutation, R117H, which
      has been observed in three phenotypes, was found to occur on two chromosome
      backgrounds with intron 8 variants that have profoundly different effects upon
      splicing efficiency. A close association is shown between chromosome background
      of the R117H mutation and phenotype. These findings demonstrate that the genetic
      context in which a mutation occurs can play a significant role in determining the
      type of illness produced.

PMID- 7506097
TI  - Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain
      in effective cytoskeleton function.
AB  - We have identified mutations in keratins K5 (Arg331Cys) and K14 (Val270Met) in
      two kinships affected by the dominantly-inherited skin blistering disease, Weber
      Cockayne epidermolysis bullosa simplex (EBS-WC). Linkage analysis, DNA sequencing
      and clinical and ultrastructural analysis are combined to provide the first
      detailed description of classical EBS-WC. Both phenotypes show similar blistering
      on trauma, indicating that both mutations compromise the structural resilience of
      the basal keratinocytes by affecting the keratin cytoskeleton. The location of
      these mutations in the L12 linker, which bisects the alpha-helical rod region of
      intermediate filament proteins, identifies another keratin mutation cluster
      leading to hereditary skin fragility syndromes.

PMID- 7506098
TI  - A role for gamma 3 hordein in the transport and targeting of prolamin
      polypeptides to the vacuole of developing barley endosperm.
AB  - Hordein synthesis, transport and deposition was analysed by immunocytochemistry
      in developing endosperm cells of wild-type (Carlsberg II) and mutant varieties
      deficient in B hordein (hor2ca), gamma 1 hordein (Donetsky), gamma 2 hordein and
      minor B hordein polypeptides (Haisa), or gamma 3 hordein (Nevsky). In all
      varieties, hordein polypeptides were detected both in the cytoplasm as globules,
      ranging in diameter from 50 nm to 1.24 microns, and in the vacuole as protein
      bodies. In the cytoplasmic globules B and C hordein polypeptides are assembled as
      a core and are surrounded by an outer layer of gamma 1 and gamma 2 hordein. The
      globules apparently fuse several times in the cytoplasm before entering the
      vacuole. Absence of gamma 3 hordein in the mutant Nevsky leads to a dramatic
      change in hordein polypeptide targeting, the hordein storage proteins being
      largely deposited in the lumen of the rough endoplasmic reticulum. gamma 3
      Hordein is unique among the sulphur-rich hordein polypeptides, being monomeric
      and forming only intramolecular disulphide bridges, while the other B and gamma
      hordein polypeptides are aggregated by intermolecular disulphide bridges.
      Retention of hordein in the rough endoplasmatic reticulum in the absence of gamma
      3 hordein suggests that gamma 3 hordein may maintain the prolamin storage
      polypeptides in a transport competent state. The sequence of the mature gamma 3
      hordein polypeptide was deduced from a cDNA clone, and compared with gamma 2
      hordein. The epitope recognized by the gamma 1 + gamma 2 hordein-specific BX
      monoclonal antibody used for immunocytochemistry was mapped to include E190 and
      K193, by synthesizing overlapping oligopeptides.

PMID- 7506099
TI  - [Transurethral microwave therapy of benign prostatic hyperplasia].

PMID- 7506100
TI  - Acanthamoeba infections of the cornea.

PMID- 7506101
TI  - Paralytic poliomyelitis--an imported case.

PMID- 7506102
TI  - Salmonella mikawasima--update.

PMID- 7506103
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7506104
TI  - Affinity gel electrophoresis of nucleic acids. Nucleobase-selective separation of
      DNA and RNA on agarose-poly(9-vinyladenine) conjugated gel.
AB  - Poly(9-vinyladenine) (PVAd) was immobilized within an agarose gel matrix to
      produce a novel affinity gel for the base-specific separation of nucleic acids by
      electrophoresis. The shape (single- or double-stranded) and base content of
      nucleic acids were specifically recognized by the affinity gel. Only single
      stranded DNA, of which the sequence is not regular enough to form a stable duplex
      hairpin structure, was selectively absorbed over double-stranded DNA. Among five
      polynucleotides having different bases such as poly(A), poly(G), poly(C), poly(U)
      and poly(I), poly(U) and poly(I) were base-specifically adsorbed by PVAd,
      probably by hydrogen bond formation. The effect of the molecular mass and size of
      poly(9-vinyladenine) was also examined.

PMID- 7506105
TI  - Affinity gel electrophoresis of nucleic acids. Specific base- and shape-selective
      separation of DNA and RNA on polyacrylamide-nucleobase conjugated gel.
AB  - Two types of affinity gels consisting of cross-linked polyacrylamide and affinity
      ligands possessing nucleic acid bases were prepared. One type of gel was
      polyacrylamide-poly(vinylnucleobase) conjugated gel, where the
      poly(vinylnucleobase) such as poly(9-vinyladenine) (PVAd) bearing a nucleobase in
      the side-chain was entrapped in the gel matrix. The other type of gel, in which a
      nucleobase such as adenine is chemically bonded to polyacrylamide gel, was
      prepared by copolymerization of acrylamide, cross-linker and 9-vinyladenine.
      These affinity gels, especially the former, demonstrated characteristic
      nucleobase- and shape-selective separation of nucleic acids. The gels showed high
      affinity for single-stranded DNA and both single- and double-stranded
      polynucleotides and could separate a double-stranded DNA in mixtures of double
      stranded DNA and polynucleotides. The electrophoretic mobilities of poly(uridylic
      acid) and poly(inosinic acid) were selectively retarded even in the presence of 7
      M urea. The electrophoretic behaviours of nucleic acids on the polyacrylamide
      PVAd conjugated gels were compared with those on the agarose-PVAd conjugated gel.
      The effects of urea, temperature and concentration of PVAd were also examined.
      The polyacrylamide-PVAd conjugated gel served to elucidate interactions between
      PVAd and nucleic acids that could not be detected by usual spectroscopic methods.

PMID- 7506106
TI  - A phosphorylation epitope on MAP 1B that is transiently expressed in growing
      axons in the developing rat nervous system.
AB  - We have isolated a monoclonal antibody (150) that recognizes a phosphorylation
      epitope on the microtubule-associated protein (MAP) 1B. Immunoblot analysis of
      the developing rat central nervous system shows that monoclonal antibody 150 is
      directed against a protein of approximately 325 kDa (MAP 1B) that copolymerizes
      with microtubules through successive cycles of temperature-dependent assembly and
      disassembly. Furthermore, immunoprecipitated MAP 1B contains the epitope
      recognized by monoclonal antibody 150. Removal of phosphate from blotted proteins
      using alkaline phosphatase abolishes the binding of monoclonal antibody 150 to
      MAP 1B, indicating that the epitope is phosphorylated. In the developing rat
      nervous system, immunohistochemistry with monoclonal antibody 150 shows that the
      phosphorylation epitope on MAP 1B is transiently expressed in growing axons but
      not in dendrites. For instance, in the neonatal rat cerebellum, the parallel
      fibres of granule cells are stained only during elongation and not after
      synaptogenesis. The monoclonal antibody 150 epitope is also transiently expressed
      in radial glial fibres and in certain cell nuclei. All immunostaining of sections
      with monoclonal antibody 150 was completely abolished by alkaline phosphatase
      treatment. These observations and previous ones made by us in cell culture
      (Mansfield et al., J. Neurocytol., 20, 654-666, 1991) suggest that the
      phosphorylation epitope on MAP 1B recognized by monoclonal antibody 150, which
      has not been previously detected in vivo, may be important in axonogenesis.

PMID- 7506107
TI  - GAP-43, aFGF, CCK and alpha- and beta-CGRP in rat spinal motoneurons subjected to
      axotomy and/or dorsal root severance.
AB  - The mRNA levels for growth-associated protein 43 (GAP-43), acidic fibroblast
      growth factor (aFGF), alpha- and beta-calcitonin gene-related peptide (CGRP),
      cholecystokinin (CCK) and choline acetyltransferase (ChAT) in rat lumbar spinal
      motoneurons were studied by in situ hybridization 1, 5 and 21 days and 20 weeks
      following unilateral peripheral nerve sectioning, ventral rhizotomy or dorsal
      rhizotomy. Furthermore, CGRP- and aFGF-like immunoreactivities in the ventral
      horn were studied using immunohistochemistry. One to 21 days after axotomy, GAP
      43 and alpha-CGRP mRNAs increased in lesioned motoneurons, while the aFGF mRNA
      levels were marginally higher in motoneurons on the lesion side as compared to
      the control side. beta-CGRP, CCK and ChAT mRNA levels, on the other hand,
      decreased during the short-term response (1-21 days) to axotomy. After ventral
      rhizotomy, but not peripheral axotomy, there was complete disappearance of aFGF
      like immunoreactivity in the ventral root proximal to the lesion. In animals
      subjected to long-term survival (20 weeks) after peripheral axotomy, the
      expression of all studied substances had returned to normal levels. Unilateral
      dorsal rhizotomy did not induce any substantial short- or long-term shifts in the
      cellular expression of the GAP-43, aFGF, CGRP and CCK peptides or their mRNAs in
      motoneurons of lesioned segments. These results indicate that peptides/proteins
      in motoneurons are expressed differentially after axotomy. Whereas alpha-CGRP and
      GAP-43 are up-regulated, CCK and beta-CGRP become down-regulated and aFGF is
      largely unaffected.

PMID- 7506108
TI  - A review on the acute phase response in major depression.
AB  - There is some evidence that major depression is characterized by systemic immune
      activation with involvement of phagocytic cells, T cell activation, B cell
      proliferation and increased autoantibody production. This paper reviews that
      major depression may be accompanied by higher concentrations of positive and
      lower concentrations of negative acute phase proteins (APPs). The most prominent
      abnormalities of APPs in major depression are increased haptoglobin (Hp) plasma
      levels. The latter are significantly and positively correlated with interleukin
      (IL)-6 production, various indices of systemic immune activation (e.g.
      monocytosis, neutrophilia, T cell activation) and with the vegetative symptoms of
      depression (e.g. anorexia, weight loss, psychomotor retardation, sleep disorders,
      anergy). Major depression is characterized by an altered distribution of Hp
      phenotypes and genes suggesting that genetic variation on chromosome 16 may be
      associated with this illness. It is concluded that increased production of IL-6
      and IL-1 in major depression may underlie both immune activation and the "acute"
      phase response in that illness, and that disorders in Hp may be related to the
      pathophysiology and pathogenesis of major depression.

PMID- 7506109
TI  - Accumulation of high level of pp60c-srcN is an early event during GM3-antibody
      mediated differentiation of neuro-2a neuroblastoma cells.
AB  - Neuro-2a neuroblastoma cells, when differentiated via a cAMP-dependent pathway by
      treatment with anti-GM3 monoclonal antibody, accumulated a high level of pp60c
      src protein and pp60c-src kinase activity just before the onset of neurite
      formation. The specific kinase activity of the accumulated c-src protein was
      found to be comparable to that of normal cerebellar neurons, but was about 6- to
      8-fold higher than that of normal astrocytes. These results, and migrations of
      peptide fragments in the SDS-polyacrylamide gels after V8 proteolysis, strongly
      indicate the accumulation of the neuron-specific isoform of the c-src protein
      (pp60c-srcN) in the GM3 antibody-treated Neuro-2a cells. Similar high levels of
      pp60c-src protein and pp60c-src kinase activity were observed in the Neuro-2a
      cells differentiated via a cAMP-dependent pathway by treatment with dibutyryl
      cAMP, but not in the same cell line when differentiated via a cAMP-independent
      pathway with 5-bromo-2'-deoxyuridine. These results demonstrate that the
      accumulation of high levels of the neuron-specific isoform of the pp60c-src
      protein (pp60c-srcN) in the Neuro-2a neuroblastoma cells depends on the specific
      signal transduction pathway involved during the differentiation of these cells.

PMID- 7506110
TI  - Evidence that substance P is utilized in medial amygdaloid facilitation of
      defensive rage behavior in the cat.
AB  - The present study was designed to test the hypothesis that a major excitatory
      mechanism for the expression of feline defensive rage behavior involves the
      medial nucleus of the amygdala which utilizes substance P as a neurotransmitter
      in a direct output pathway that supplies the medial hypothalamus. In phase I of
      the experiment, stimulating electrodes were implanted into the medial amygdala
      and cannula electrodes were implanted into the medial and lateral hypothalamus
      from which defensive rage and predatory attack behavior could be elicited by
      electrical stimulation, respectively. Response latencies for defensive rage were
      significantly lowered after dual stimulation of the medial amygdala and medial
      hypothalamus relative to single stimulation of the medial hypothalamus alone. In
      phase II, dose- and time-dependent decreases in medial amygdaloid-induced
      facilitation of defensive rage were observed after the i.p. administration of the
      NK1 antagonist, CP-96,345 (0.05, 2 and 4 mg/kg). In phase III of the study, the
      effects of microinjections of CP-96,345 placed directly into defensive rage sites
      within the medial hypothalamus (0.05, 0.5 and 2.5 nmol) upon medial amygdaloid
      modulation of this response were assessed. Again, intracerebral administration of
      this antagonist blocked the facilitatory effects of medial amygdaloid-induced
      facilitation of defensive rage in a manner parallel to that observed with
      peripheral administration of the NK1 antagonist. The results suggest that the
      medial amygdala facilitates defensive rage by acting through a substance P
      mechanism at the level of the medial hypothalamus. Other experiments revealed
      that peripheral administration of the NK1 antagonist: (1) had little upon the
      latency or threshold for elicitation of defensive rage, suggesting that the
      medial amygdaloid-substance P facilitatory mechanism acts in a phasic rather than
      tonic manner; and (2) also blocks the suppressive effects of medial amygdaloid
      stimulation upon predatory attack behavior elicited from the lateral
      hypothalamus. The latter finding suggest that similar neurochemical mechanisms
      regulate medial amygdaloid modulation of both forms of hypothalamically elicited
      aggression. The final aspect of this study utilized the combination of retrograde
      tracing of amygdaloid neurons into the medial hypothalamus after microinjections
      of Fluoro-Gold into defensive rage sites, and the immunocytochemical analysis of
      substance P neurons within the amygdala. The data indicated that large numbers of
      retrogradely and immunocytochemically positive labeled cells were identified in
      the medial nucleus, including many that were double-labeled.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7506111
TI  - The connectivity of the area postrema in the ferret.
AB  - The area postrema (AP) is the chemosensitive trigger zone for the emetic reflex.
      We have investigated the connectivity of the AP and adjacent solitary complex
      (SC) to identify possible sites of the motor emetic center. The AP and SC were
      infused with HRP or WGA-HRP in 30 ferrets that were perfused transcardially after
      24-72 h. A block from the pons to upper cervical spinal cord, and one with
      hypothalamus and basal forebrain, was cut at 50 microns, reacted, and mounted.
      Data support the conclusion, at variance with those from other preparations, that
      in ferrets the AP has reciprocal connections only with the SC, which serves as a
      relay in both ascending and descending pathways between AP and higher levels of
      the neuraxis. Connectivity of the SC with brain stem and forebrain structures
      including the rostral ventrolateral medulla, parabrachial nuclei, paraventricular
      nucleus, and amygdala was demonstrated. At least in ferrets, our results suggest
      that the motor emetic center must be located within the SC. While this may not
      apply to all species, it is also possible that some reports of AP projections
      elsewhere were results of label within the SC. Alternatively, the somewhat
      different pattern of emesis in the ferret as compared to the dog (greater role
      for vagal inputs in response to radiation and cytotoxic drugs, lesser role for
      humoral inputs) may reflect differences in AP connectivity.

PMID- 7506112
TI  - The central connections of the vagus nerve in the ferret.
AB  - The vagus nerve mediates emesis due to gastric irritation. The central
      representation of the vagus in the ferret was studied to establish how the nerve
      is connected to areas important in the regulation of emesis. In a series of 10
      ferrets, WGA-HRP injections (10 microliters) were made into the nodose ganglion.
      After 24-48 h, animals were reanesthetized and perfused transcardially. A block
      extending from the pons to upper cervical spinal cord was cut at 50 microns and
      sections reacted. Nodose ganglion injections of WGA-HRP produced labeling of
      vagal preterminal segments in the ipsilateral dorsal vagal complex including all
      subnuclei of the solitary complex where the medial and subgelatinous subnuclei
      received the densest input, the area postrema (AP), which contained a modest
      amount of terminal label, and the dorsal motor nucleus of the vagus (DMX).
      Contralateral terminal label, quantitatively much less, was similarly distributed
      except that within the solitary complex it was limited to the medial and
      subgelatinous subnuclei. Retrogradely labeled cells formed ipsilateral
      dorsomedial and ventrolateral columns, corresponding, respectively, to the DMX
      and the nucleus ambiguus (including retrofacial and retroambiguus).

PMID- 7506113
TI  - Selective agonists at NK3 tachykinin receptors inhibit alcohol intake in
      Sardinian alcohol-preferring rats.
AB  - The present study evaluated the effect of tachykinin agonists, selective for
      different neurokinin (NK) receptors, on alcohol intake in genetically selected,
      Sardinian alcohol-preferring rats. Tachykinins were given by
      intracerebroventricular injection just before access to fluids. In rats offered
      both water and 8% ethanol 2 h/day, the NK3 selective agonists
      [Asp5.6,MePhe8]substance P(5-11), Suc[Asp6,MePhe8]substance P(6-11), and
      [MePhe7]neurokinin B markedly suppressed alcohol intake. The NK1 selective
      agonist [Sar9,Met(O2)11]substance P and the NK2 selective agonist GR 64349 did
      not At doses that inhibited alcohol intake, the NK3 agonists did not modify water
      intake; total fluid intake was significantly reduced only following 500 ng/rat of
      [Asp5.6,MePhe8]substance P(5-11). When rats were given a longer access to fluids
      (8% alcohol for 2 h, but water for 4 h), again, NK3 agonists suppressed alcohol
      intake, but not total fluid intake. Moreover, NK3 agonists did not modify solid
      food intake in food-deprived rats, nor water intake in water-deprived rats, when
      alcohol was not available. These findings indicate that NK3 agonists inhibit
      alcohol intake in Sardinian alcohol-preferring rats and that their effect is
      behaviorally selective. They also suggest that central NK3 receptors may be
      involved in alcohol intake control in rats.

PMID- 7506114
TI  - Long-term survival associated with metastatic small cell carcinoma of the
      esophagus treated by chemotherapy, autologous bone marrow transplantation, and
      adjuvant radiation therapy.
AB  - A 44-year-old woman had small cell carcinoma of the esophagus complicated by
      liver and lymph node metastases. She was treated with aggressive combination
      chemotherapy, followed by autologous bone marrow transplantation and adjuvant
      radiation therapy. (The authors believe this to be the first use of autologous
      bone marrow transplantation for treatment of this condition.) This regimen
      resulted in apparent complete regression of the disease as documented by computed
      tomography and endoscopic study. Three years later, she again experienced general
      malaise and was found to have extensive recurrent disease in the lung, bone, and
      liver. Her condition deteriorated rapidly, and she died within 1 month. A review
      of the literature reveals that this patient survived longer than any others who
      have had this rare but aggressive tumor. The authors suggest that this form of
      therapy should be considered for future patients.

PMID- 7506115
TI  - Chemosensitivity testing of human malignant melanoma. A retrospective analysis of
      clinical response and in vitro drug sensitivity.
AB  - BACKGROUND: Clinical response rates in the treatment of patients with
      disseminated malignant melanoma are low and unpredictable. Several reports have
      documented that clonogenic assay systems for in vitro drug testing are capable of
      predicting resistance to therapy in vivo and might provide guidelines to improve
      clinical response rates. METHODS: Specimens from metastatic lesions of patients
      with malignant melanoma, predominantly from lymph nodes and skin, were
      disaggregated, exposed to a panel of 10 cytotoxic drugs for 1 hour, and
      subsequently cultured in agarose. Effects were calculated by the ability to form
      tumor colonies compared with an untreated control after 7-14 days. A
      retrospective comparison between the in vitro drug testing result and clinical
      response was possible in 19 cases. RESULTS: An average of 7.3 drugs per specimen
      were tested. A high degree of resistance was observed against all cytostatic
      agents studied independently of the tumor site. In 47 of 181 in vitro drug tests,
      tumor colony formation was reduced by 30-50%; in 17 of 181, the reduction was
      more than 50%. A retrospective analysis showed no clinical response in 11 cases
      and one mixed response in which patients received drugs that had been shown to be
      "resistant" in vitro. CONCLUSIONS: These results support the concept that in
      vitro drug testing promises to help avoid treatment with ineffective drugs and
      their associated toxic side effects. Furthermore, it may increase the likelihood
      of obtaining a clinical response in the treatment of disseminated malignant
      melanoma. The major limitation in the treatment of malignant melanoma is the lack
      of availability of effective agents for treatment.

PMID- 7506117
TI  - Collision of transitional cell carcinoma and renal cell carcinoma. An
      immunohistochemical study and review of the literature.
AB  - A case characterized by a rare synchronous occurrence of transitional cell
      carcinoma (TCC) of the renal pelvis and renal cell carcinoma (RCC) in the same
      kidney is presented. A retrospective analysis of 23 similar cases reported in the
      English literature over the last 71 years demonstrated a male-to-female ratio of
      2:1, an average age of 64.5 years, and a left-to-right-side ratio of 3.2:1. The
      three most common findings at initial examination were hematuria (90%), flank
      pain (19%), and flank mass (14%). Moreover, 24% of patients had tumor metastases
      even at initial examination. Thirty-four percent of patients had bladder
      neoplasms, and 24% of them had a history of cigarette smoking. There is no
      tendency toward higher grade of malignancy or specific histologic pattern for TCC
      and RCC when they occur together in the same kidney. Immunohistochemical studies
      were used to examine TCC and RCC, with special attention paid to the site of
      their collision, which displayed multifocal lymphatic permeation. Both TCC and
      RCC were positive for epithelial membrane antigen (EMA) and cytokeratins
      identified by monoclonal antibodies CAM-5.2, AE1/AE3, and MAK-6. TCC was focally
      positive for keratin, detectable by antibody 34 beta E12, but RCC was not. The
      tumor tissue infiltrating the lymphatics, which seemed to be RCC, demonstrated
      positive staining for EMA and keratins CAM-5.2, AE1/AE3, and MAK-6 and negative
      staining for keratin 34 beta E12. Interestingly, the tumor in lymphatics
      displayed strong staining for carcinoembryonic antigen (CEA) but both TCC and RCC
      in the vicinity were negative. These findings suggest that keratin 34 beta E12
      may play a role in the differential diagnosis between TCC and RCC and that tumor
      invading lymphatics may change phenotype, including the neoexpression of CEA.

PMID- 7506116
TI  - Prognostic significance of the overexpression of c-erbB-2 protein in
      adenocarcinoma of the uterine cervix.
AB  - BACKGROUND: The overexpression of c-erbB-2 protein is a prognostic marker in
      patients with breast cancer. Alteration of the c-erbB-2 oncogene in development
      of adenocarcinoma of the uterine cervix, an unfavorable gynecologic neoplasm, is
      unknown. METHODS: To clarify the role of the c-erbB-2 oncogene in adenocarcinoma
      of the uterine cervix, formalin-fixed, paraffin-embedded tissue sections from 44
      cases of cervical adenocarcinoma were immunohistochemically examined for
      expression of c-erbB-2 protein and for c-erbB-2 gene amplification in DNA by slot
      blot-hybridization analysis. RESULTS: The expression of c-erbB-2 protein was
      detected in 34 cases (77%). Strong expression on cell membranes was detected in
      11 cases (25%). Most cases with strong membrane expression of c-erbB-2 protein
      also showed amplification of the c-erbB-2 gene by slot blot-hybridization.
      Expression of the protein on cell membranes was more often seen at clinical Stage
      II or III (9 of 23 [39%]) than at Stage 0 or 1 (2 of 21 [9%]) (P < 0.05, Fisher's
      exact test). Expression of the c-erbB-2 protein was also associated with poorer
      prognosis of patients with cervical adenocarcinoma by comparison of survival
      curves (P < 0.005) and by the Cox regression model analysis. CONCLUSIONS:
      Overexpression of c-erbB-2 protein is associated with amplification of c-erbB-2
      gene and frequently occurred in cervical adenocarcinomas of the patients with
      poor prognoses.

PMID- 7506118
TI  - Allelotype and loss of heterozygosity of p53 in primary and recurrent
      hepatocellular carcinomas. A study of 150 patients.
AB  - BACKGROUND: The allelotype and loss of heterozygosity (LOH) of the p53 gene in
      human hepatocellular carcinoma (HCC) were studied in 150 patients with resected
      primary HCC and 18 with recurrent HCC. METHODS: DNA samples of paired HCC and
      livers were cut with BanII enzyme for the study of p53 allelotype and allele
      loss. The medical records of the patients were carefully reviewed. RESULTS: Sixty
      four (42.7%) patients were heterozygous for the p53 gene, 69 (46%) were
      homozygous for the 1.5/1.4 kb small (S) allele, and 17 (11.3%) were homozygous
      for the 2.9 kb large (L) allele. The frequencies of the minor L allele (0.323)
      and of the major S allele (0.677) in this population of Chinese patients differed
      from the frequencies previously reported for North American Caucasians (0.13 and
      0.87, respectively). The heterozygous patients tended to have lower serum
      hepatitis B surface- and e antigens (HBsAg and HBeAg) and higher diabetes
      mellitus (DM) than did homozygous patients (SS and LL). Thirty-seven (57.8%) of
      the 64 heterozygous patients had a tumor-specific p53 allele LOH, being two times
      more common in HCC tumors larger than 8 cm than in HCC tumors 2 cm or smaller.
      The frequency of DM was four times higher in the heterozygous patients who had
      p53 LOH than in those who retained both alleles. LOH of p53 did not correlate
      with tumor invasiveness or differentiation, hepatitis B or C virus infection, or
      prognosis. CONCLUSION: The allelotype of p53 gene in HCC correlates with HBsAg
      and HBeAg seropositivities and DM. LOH of the p53 gene is a common event in HCC,
      correlates with DM, and occurs less often in familial HCC. LOH can identify the
      clonal origin of recurrent HCC but is not a critical prognostic factor.

PMID- 7506119
TI  - A low prevalence of anti-hepatitis C virus antibody in patients with
      hepatocellular carcinoma in Guangxi Province, southern China.
AB  - BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in southern China,
      including Guangxi Province, is among the highest in the world. Investigations of
      the etiology of HCC in this area have focused on hepatitis B virus (HBV) and
      aflatoxin. However, hepatitis C virus (HCV) has been shown to be a possible
      pathogenic agent for HCC in a number of countries. METHODS: Antibodies to HCV
      (anti-HCV), determined by second-generation enzyme immunoassay, and hepatitis B
      surface antigen (HBsAg) were assayed in the sera of 186 patients with HCC and 48
      healthy control subjects from Guangxi Province in southern China. RESULTS: HBsAg
      was detected in 131 (70.4%) of 186 patients with HCC, whereas only 10 (5.4%)
      patients were found to be positive for anti-HCV. The prevalence of anti-HCV in
      patients with HBsAg-positive HCC was 6.9% (9 of 131) and that in patients with
      HBsAg-negative HCC was 1.8% (1 of 55); there was no significant difference
      between these two groups. Anti-HCV was not detected in any of the healthy control
      subjects, in whom the prevalence of HBsAg was 10.4% (5 of 48). CONCLUSIONS: These
      findings indicate that HCV does not seem to play an important role in the
      development of HCC in Guangxi Province; however, HBV infection appears to be a
      major pathogenic factor for HCC in this area.

PMID- 7506120
TI  - Expression of bone morphogenetic proteins in human osteosarcoma.
      Immunohistochemical detection with monoclonal antibody.
AB  - BACKGROUND: Bone morphogenetic proteins (BMP) induce ectopic bone formation in
      vivo and may play a role in normal bone development. In addition, bone
      morphogenetic activity, as measured in a bone-forming assay in immunodeficient,
      athymic nu/nu mice, is present in a proportion of osteosarcomas; this activity,
      which may be mediated by BMP, is correlated with a poor prognosis. METHODS: The
      development of a monoclonal antibody against recombinant human BMP-2, AbH3b2/17,
      has allowed immunohistochemical localization of BMP in tumor tissues. Cryostat
      sections of osteosarcomas (21 tumor samples), chondrosarcomas (5 samples), and
      Ewing's sarcomas of bone (5 samples) were examined with AbH3b2/17 using the
      avidin-biotin-immunoperoxidase method. RESULTS: The authors found AbH3b2/17
      immunoreactivity in 12 of the 21 osteosarcoma samples (57% sensitivity) obtained
      from 20 patients. For one patient, samples of the primary lesion and a subsequent
      metastasis were tested, and only the latter showed AbH3b2/17 immunoreactivity.
      The chondrosarcomas and Ewing's sarcomas examined showed no immunoreactivity. In
      antigen-positive osteosarcomas, AbH3b2/17 immunostaining was localized
      predominantly in the cytoplasm of tumor cells. Moreover, the proportion of
      AbH3b2/17-reactive cells varied among osteosarcomas with disparate histologic
      features. CONCLUSIONS: The authors identified a rapid and widely applicable
      method for detecting BMP expression in intact tissues, which may complement and
      enhance the bone-forming assay in nu/nu mice as a prognostic procedure in
      osteosarcomas.

PMID- 7506121
TI  - Molecular cloning and characterization of alternatively spliced transcripts of
      the mouse neurofibromatosis 2 gene.
AB  - The human neurofibromatosis 2 (NF2) gene has recently been isolated and predicted
      to encode a novel protein named merlin. Based on its high homology to the moesin
      ezrin-radixin family of proteins, it may be involved in mediating interactions
      between the plasma membrane and the cytoskeleton. Here we report the isolation
      and characterization of multiple transcript isoforms of the mouse NF2 gene. The
      full length coding complementary DNA sequence of transcript isoform I is 1788
      base pairs in length, shares 90% sequence identity with the human NF2
      complementary DNA, and encodes a putative protein of 596 amino acids sharing 98%
      homology with the human merlin protein. Transcript isoforms II and III carry a 45
      and 16-base pair insertion, respectively, at nucleotide 1740 at the 3' end,
      generated by two different modes of alternative splicing; both insertions
      introduce premature termination codons. Thus, transcript isoforms II and III
      predict proteins of 591 and 584 amino acids with altered COOH-termini of more
      hydrophilic character as compared to isoform I. Northern blot analysis and
      reverse transcription-polymerase chain reaction analysis indicate that the mouse
      NF2 gene is widely expressed in different tissue types and that the alternative
      transcripts are variantly expressed. The results presented here indicate high
      conservation of the NF2 gene during evolution and suggest a possible role for the
      COOH-terminus in mouse merlin function.

PMID- 7506122
TI  - Potential use of soluble CD44 in serum as indicator of tumor burden and
      metastasis in patients with gastric or colon cancer.
AB  - Soluble CD44 is present in the serum of normal individuals (2.7 +/- 1.1 nM). The
      concentration of soluble CD44 in the serum is elevated in patients with advanced
      gastric (24.2 +/- 9.8 nM) or colon cancer (30.8 +/- 11 nM). Serum CD44
      concentration correlated with tumor metastasis and tumor burden. Surgical
      resection of tumors resulted in decreases in serum CD44 levels. By Western blot
      analysis, monoclonal anti-CD44 antibody reacted with a major protein with
      molecular weight between 130,000 and 190,000. In addition, two proteins with
      molecular weights of 72,000 and 80,000 can also be identified. Therefore,
      different CD44 isoforms may be present in the serum of cancer patients. Serum
      CD44 concentrations may be an indicator of tumor burden and metastasis in
      patients with malignant diseases.

PMID- 7506123
TI  - Combinations of stem cell factor with other hematopoietic growth factors enhance
      growth and sensitivity to cytosine arabinoside of blast progenitors in acute
      myelogenous leukemia.
AB  - The blast progenitors in acute myelogenous leukemia grow in response to
      hematopoietic growth factors (HGFs), and their sensitivity to antileukemic drugs
      is influenced by HGFs. We report the effects of stem cell factor (SCF) on the
      growth and sensitivity to 1-beta-D-arabinofuranosylcytosine (Ara-C) of blast
      progenitors in acute myelogenous leukemia. SCF stimulated both colony formation
      and self-renewal of blast progenitors and, when used in combination with other
      HGFs, synergistic enhancement of colony formation was noted in 8 of the 15
      patients examined. Cell fractionation studies demonstrated no unique growth
      dependency on SCF in either CD34+ or CD34- populations. Blast cells of patients
      that displayed synergistic growth enhancement with SCF displayed the highest Ara
      C sensitivity when HGFs were used in combination with SCF. The tritiated
      thymidine suicide test (20-min exposure) revealed that the proportion of blast
      progenitors in the S phase of the cell cycle was highest when SCF and another HGF
      were simultaneously present, although 24-h exposure killed most or all of the
      blast progenitors. These data indicate that SCF enhances growth and sensitivity
      to Ara-C of acute myelogenous leukemia blast progenitors in a closely correlated
      fashion and that the cell cycle changes as well as other mechanisms are involved
      in the Ara-C sensitivity modulation by SCF.

PMID- 7506124
TI  - Chimerization of antitumor antibodies via homologous recombination conversion
      vectors.
AB  - Homologous recombination vectors were designed to convert murine hybridoma cell
      lines expressing IgG3, IgG1, or IgG2a heavy chains into chimeric human IgG1
      producers. These conversion vectors included homology both upstream and
      downstream of the target sequences and consistently resulted in a higher
      frequency of successful gene targeting than an insertion vector bearing a single
      region of homology. A human kappa light chain conversion vector was also
      constructed and used to complete chimerization of the anticarcinoma hybridoma
      cell line BR96. The resulting cell line expressed antigen-specific chimeric
      antibody at comparable levels to those found in the murine parental cell line.
      Southern blots confirm that recombination occurred within the upstream and
      downstream regions of homology for both vectors, resulting in the loss of murine
      constant region sequences.

PMID- 7506125
TI  - MDA-MB-134 breast carcinoma cells overexpress fibroblast growth factor (FGF)
      receptors and are growth-inhibited by FGF ligands.
AB  - Overexpression of some transmembrane tyrosine kinase growth factor receptors in
      breast and other tumors has been found to correlate with poor prognosis.
      Following the cloning of the first two members of the fibroblast growth factor
      family of receptors (FGFRs), amplification of these receptors in breast
      carcinomas was found. We have examined 23 breast carcinoma cell lines to
      determine the extent of expression of mRNA for fgfrs 1 through 4. All breast
      carcinoma cell lines examined expressed mRNA for at least one fgfr and several
      expressed high mRNA levels for a particular receptor. MDA-MB-134, an estrogen
      receptor-positive cell line, expressed very high levels of mRNA for fgfr-1 and
      elevated levels of mRNA for fgfr-4. This cell line was found to have an amplified
      fgfr-1 gene, but the gene for fgfr-4 was not amplified. MDA-MB-453 cells were
      found to express high levels of mRNA for fgfr-4 without amplification of the
      gene. MDA-MB-134 cells were examined for their response to FGF ligands. Tyrosine
      phosphorylation of a M(r) 150,000 protein resulted when MDA-MB-134 cells were
      treated with FGF-1 or FGF-2, implying the presence of a functional FGFR-1. MDA-MB
      134 cells were growth-inhibited by picomolar concentrations of FGF-1 or FGF-2 in
      a dose-dependent manner under both anchorage-independent and anchorage-dependent
      conditions. These results may provide insight into the consequences of FGFR
      overexpression in breast tumors and the development of treatment modalities which
      use manipulation of growth factor responses.

PMID- 7506126
TI  - In vitro protective effects of chemopreventive agents against bleomycin-induced
      genotoxicity in lymphoblastoid cell lines and peripheral blood lymphocytes of
      head and neck cancer patients.
AB  - The protective effects of ascorbic acid (AA), n-acetyl-l-cysteine (NAC), alpha
      tocopherol acid (ATA), alpha-tocopherol-acid succinate (TAS), and 13-cis-retinoic
      acid (CRA) on mutagen-induced chromosomal breakage were studied. Mutagen
      sensitivity was determined by the bleomycin assay in human lymphoblastoid cell
      lines (LCLs) and cultures of peripheral blood lymphocytes (PBLs) from head and
      neck cancer patients. Preincubation with chemopreventive agents statistically
      significantly decreased mutagen-induced chromatid breakage in LCLs and PBLs in a
      dose-related manner. As the concentration of the agents was increased in tenfold
      increments in the study range, mean breakage rates were reduced by 3.0 to 7.7% in
      LCLs and by 6.0 to 11.1% in PBLs. The effective concentrations are comparable to
      those achieved in clinical applications and found in human dietary studies. A
      similar phenomenon in vivo, if identified, may explain the differences in
      occurrence of head and neck and other cancers between populations with different
      dietary habits. The bleomycin assay may be used for studying compounds with
      presumed chemopreventive properties.

PMID- 7506127
TI  - Electrophysiology of human cardiac cells.

PMID- 7506128
TI  - Ryanodine sensitive calcium release channel from left ventricle, septum, and
      atrium of canine heart.
AB  - OBJECTIVE: The aim was to consider the possibility that functionally distinct
      forms of the ryanodine sensitive calcium release channel are expressed in
      different regions of heart. METHODS: Membranous fractions enriched in ryanodine
      binding activity were isolated from canine left ventricular free wall,
      interventricular septum, and atrium. Ryanodine receptors (RyR) were purified by
      sucrose density gradient centrifugation, following solubilisation of sarcoplasmic
      reticular membranes with the detergent Chaps. Single channel currents were
      measured, upon reconstitution of sarcoplasmic reticular vesicles and the purified
      RyR into planar lipid bilayers. RESULTS: Ryanodine sensitive Ca2+ release
      channels from three different regions of canine heart displayed the same
      [3H]ryanodine binding and single channel characteristics. CONCLUSIONS: The left
      ventricular free wall, septum, and atrium of canine heart may express
      functionally related, if not identical, ryanodine receptor/Ca2+ release channels.

PMID- 7506129
TI  - Application of molecular and cytogenetic techniques to the detection of a de novo
      unbalanced t(11q;21q) in a patient previously diagnosed as having monosomy 21.
AB  - The occurrence of complete autosomal monosomy in man is extremely rare and
      generally considered to be incompatible with life. Since the introduction of
      banding techniques in human cytogenetics, several cases of presumptive monosomy
      for chromosome 21 have nevertheless been reported. However, it has been suggested
      that most, if not all, of these cases may represent unbalanced translocations or
      other structural aberrations resulting in only partial monosomy 21. Here we
      described a patient in whom full monosomy 21 was initially diagnosed by routine
      karyotyping. Re-examination with a combination of high resolution banding
      technique, chromosome painting and DNA polymorphism analysis demonstrated the
      presence of an unbalanced translocation between the long arms of chromosome 11
      and 21, respectively. Consequently, the case was re-classified as a partial
      monosomy for the proximal long arm of chromosome 21.

PMID- 7506130
TI  - Anti-RA 33 antinuclear autoantibody in rheumatoid arthritis and mixed connective
      tissue disease: comparison with antikeratin and antiperinuclear antibodies.
AB  - Besides rheumatoid factor (RF), antikeratin antibodies (AKA) and antiperinuclear
      factor (APN), anti-RA 33 antibody has been described as a highly specific
      antinuclear antibody for rheumatoid arthritis (RA). In this study RA 33
      antibodies were detected using Western blotting with HeLa cell nuclear extract in
      a group of 94 RA patients and 259 controls. Anti-RA 33 was present in 35% of 94
      RA patients, with a similar frequency in RF positive (32%) and RF-negative (45%)
      RA patients. RA-33 antibody was also present in 60% of a group of 30 patients
      with anti-U1 RNP positive mixed connective tissue disease. The specificity of
      anti-RA 33 for RA was 84.6%. Anti-RA 33 antibody was already present in sera from
      23.5% of 18 patients with RA of less than one year's duration. Anti-RA 33
      antibody was the only positive immunological marker in 3/20 cases of seronegative
      adult RA. No correlations were found between anti-RA 33 antibody and AKA or APF.
      Patients with erosive RA and patients whose ESR was > or = 50 mm after 1 hour
      were more likely to be anti-RA 33 positive (47.6% vs 24.4% and 42.8% vs 29.4%).
      These results suggest that anti-RA 33 antibody, in the absence of anti-U1-RNP
      antibodies, can be added to the list of the helpful serological markers for
      rheumatoid arthritis.

PMID- 7506131
TI  - Raised endothelial cell stimulating angiogenesis factor in ankylosing
      spondylitis.
AB  - Endothelial cell stimulating angiogenesis factor (ESAF) is important in the
      neovascularisation that precedes new bone formation, and raised levels are found
      in association with healing fractures and osteoarthritis. We investigated its
      relevance to the new bone growth that is found at inflammatory sites in
      ankylosing spondylitis (AS). Forty-one patients with AS were studied clinically
      and radiographically and had their serum ESAF levels measured. In comparison to
      age-matched controls the AS patients had significantly raised ESAF levels (p <
      0.0001). Within the AS group, patients with relatively higher ESAF levels had no
      characteristic clinical or radiological features.

PMID- 7506132
TI  - Current management of carcinoma of the esophagus.

PMID- 7506134
TI  - On the management of malignant pleural effusions.

PMID- 7506133
TI  - Cytokeratins 8, 18 and 19 in endometrial epithelial cells during the normal
      menstrual cycle and in women receiving Norplant.
AB  - Cytokeratins 8, 18 and 19 are members of the cytoskeletal intermediate filament
      protein family. They are expressed in all simple epithelial tissues, including
      endometrium, and are recognised as dynamic structures that can be affected by
      numerous external factors. The Norplant system is a subdermal slow release
      levonorgestrel implant commonly used as a long-acting progestogen contraceptive.
      Norplant implants have been shown to have atrophic effects on endometrial
      epithelial and stromal cells, and cause a range of endometrial bleeding problems
      among users. The aim of this study is to describe changes in the
      immunohistochemical expression and distribution of cytokeratins 8, 18 and 19 in
      endometrial epithelial cells of Norplant implants users and normal menstrual
      cycle controls. Endometrial biopsies were collected from 65 control normal cycle
      women and 37 Norplant implants acceptors. The normal menstrual cycle was
      classified histologically into 9 stages; one menstrual, five proliferative and
      three secretory. Norplant implants bleeding patterns were categorised into 6
      groups according to current World Health Organisation (WHO) definitions;
      amenorrhoea, frequent bleeding, infrequent bleeding, irregular bleeding, "normal"
      bleeding, and prolonged bleeding. The tissues were fixed in formalin, embedded in
      paraffin, and stained immunohistochemically. Semi-quantitative scoring of the
      staining intensity was performed. Apical versus basal intracellular cytokeratin
      distribution was also evaluated. The staining intensity was significantly
      stronger in control endometrial tissue compared to Norplant implants tissue. In
      control tissues, cytokeratins were predominantly located in the apical region of
      epithelial cells (52% of biopsies) and in Norplant implants tissues they were
      predominantly distributed equally between the apical and basal portions of
      epithelial cells (43% of biopsies). There was no particular cytokeratin
      distribution pattern associated with the different stages of normal cycle or the
      different Norplant implants bleeding patterns. It was concluded that long-term
      exposure to levonorgestrel significantly reduced the cytokeratin expression in
      endometrial epithelial cells (P < 0.001).

PMID- 7506135
TI  - Role of early postoperative surface echocardiography in the pediatric cardiac
      intensive care unit.
AB  - OBJECTIVE: To compare surface echocardiographic data with catheterization and
      surgical observation as a way of deciding on the need to reoperate to correct
      hemodynamically important sequelae following pediatric cardiac surgery; to
      determine the false-negative diagnosis rate of surface echocardiography. DESIGN:
      Case series. SETTING: Tertiary-care center, pediatric cardiac intensive care
      unit. PATIENTS: All 39 patients who underwent reoperation because of
      hemodynamically significant anatomic sequelae following primary or elective
      secondary surgery in 1 calendar year. INTERVENTIONS: None. MEASUREMENTS: Two
      dimensional and color Doppler ultrasound assessment of anatomy and physiology
      following cardiac surgery. RESULTS: In 85 percent, surface echocardiography
      provided sufficient information for surgeons to reoperate on the same admission.
      Detection of important residual shunts or arterial stenoses and identification of
      anatomic causes of pulmonary undercirculation (or overcirculation) in palliated
      single ventricle are feasible. CONCLUSION: Early postoperative surface
      echocardiography is a viable way to decide on the hemodynamic adequacy of cardiac
      surgery.

PMID- 7506136
TI  - Flow cytometric analysis and cytokeratin typing of human lung tumors. A
      preliminary study.
AB  - In the current study a comparative analysis of keratin typing and DNA content was
      carried out in human lung tumors from transthoracic fine needle aspiration
      biopsies (TFNAB) (18 patients) or from surgically resected tumor tissues (14
      patients). According to the cytologic and histologic features, 2 of the 32 tumors
      were diagnosed as benign tumors, 11 as squamous cell carcinomas, 12 as
      adenocarcinomas, and 7 as undifferentiated large cell carcinomas. Two cases in
      the adenocarcinoma and one in the undifferentiated large cell carcinoma groups
      were pulmonary metastasis or second primary tumors. Malignant cells of tumors
      which reacted positively with KK8.60 anticytokeratin polypeptides No. 10 and 11
      (and hence contain keratinizing cells) displayed diploid DNA content in a flow
      cytometric assay regardless of their cytologic or histologic appearance. In
      contrast, all tumors which lacked such positive cells (most of which were defined
      as adenocarcinomas and undifferentiated tumors) were hyperdiploid. The close
      correlation between high DNA content and both malignancy and the absence of
      advanced squamous differentiation (keratinization) suggests that such combined
      analysis may provide new tools for the cytologic diagnosis and prognosis of lung
      cancers.

PMID- 7506137
TI  - Pleural multicystic mesothelial proliferation.
AB  - We report a rare case of pleural multicystic mesothelial proliferation occurring
      in a 62-year-old Japanese woman. Macroscopically, the lesion consisted of
      multiple thin wall cysts containing clear serous fluid. Histologic studies,
      including hematoxin-eosin stain, as well as the immunohistochemical method,
      revealed that the lesion was mesothelial in origin and consistent with a reactive
      change.

PMID- 7506138
TI  - Effect of prefrontal cooling on levels of glutamate, DOPAC and 5-HIAA in nucleus
      accumben and striatum in vivo.
AB  - The effect of pre-frontal cooling of the cortex (PFC) on monoaminergic
      metabolites (DOPAC and 5-HIAA) and excitatory amino acids (glutamate (Glu) and
      aspartate (Asp)) was investigated using microdialysis in rat striatum (Str) and
      nucleus accumben (NuAc). The cooling profoundly decreased Glu and elevated DOPAC
      and 5-HIAA in both Str and NuAc for a long period of time. However, the time
      course of the detection of each compound appeared different between Str and NuAc.
      In NuAc, Glu decreased rapidly to reach the plateau in about 30 min; however, in
      Str, Glu decreased steadily and reached the plateau in about 60 min. The time
      courses of elevation of 5-HIAA and DOPAC were also quite different between Str
      and NuAc; there was more profound change observed in Str than in NuAc. The level
      of DOPAC exhibited a similar period of increase (7.14 min) in NuAc and Str but in
      NuAc it decreased toward the baseline much earlier (about 2h) than Str (over 3
      h). The level of 5-HIAA in Str showed a period of rapid increase to a plateau
      (less than 42 min) but a trend of decrease started before the termination of
      sampling. In NuAc, in contrast, 5-HIAA increased slowly (more than 48 min) and
      maintained a plateau until termination of sampling. We conclude that PFC cooling
      may have caused an increase in Glu secretion and resulted in the release of the
      tonic restraint on DA terminals in both Str and NuAc, thus increases the synaptic
      turnover of monoamines.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506139
TI  - FGF-4 regulates expression of Evx-1 in the developing mouse limb.
AB  - We describe here the temporal and spatial pattern of expression of Evx-1, a
      murine homolog of the Drosophila even-skipped gene, in the developing limb bud.
      Evx-1 RNA is first detected in distal limb (progress zone) mesenchyme shortly
      after the formation of the apical ectodermal ridge. The level of Evx-1 RNA
      increases during the next 24 hours of development, and then decreases in the
      subsequent 24 hours, such that by the time the ridge regresses Evx-1 RNA is
      undetectable. At all these stages, Evx-1 RNA is localized primarily to the
      posterior distal mesenchyme, in the region immediately underlying that portion of
      the ridge in which the Fgf-4 gene is expressed. Using an in vitro culture system,
      we show that the ridge is required for both the induction and maintenance of Evx
      1 expression in the distal mesenchyme. We also demonstrate that in the absence of
      the ridge, FGF-4, as well as other FGF proteins, can induce Evx-1 expression in
      the limb bud. However, this effect appears to be indirect, since it can be
      blocked by an inhibitor of protein synthesis. Additional studies demonstrate that
      the effect of FGF-4 on Evx-1 expression is modulated by BMP-2. These data serve
      to identify Evx-1 as a downstream gene in the FGF signal transduction pathway in
      the limb.

PMID- 7506140
TI  - Stem cell factor induces outgrowth of c-kit-positive neurites and supports the
      survival of c-kit-positive neurons in dorsal root ganglia of mouse embryos.
AB  - The c-kit receptor tyrosine kinase is highly expressed by about 10% of the
      neurons in the dorsal root ganglia (DRGs) of mouse embryos. We investigated the
      in vitro effect of stem cell factor (SCF), the ligand for c-kit receptor, on
      DRGs. Recombinant murine SCF (rmSCF) induced the outgrowth of c-kit-positive
      neurites from DRGs of normal (+/+) embryos. The effect of SCF was dose dependent
      and completely abolished by anti-c-kit ACK2 monoclonal antibody (mAb). Some
      neurites whose outgrowth was induced by nerve growth factor (NGF) were c-kit
      positive, but anti-NGF mAb did not inhibit the rmSCF-induced neurite outgrowth.
      rmSCF did not induce neurite outgrowth from DRGs of W/W embryos that did not
      express c-kit receptors on the cell surface and of W42/W42 mutant embryos that
      expressed c-kit receptors without tyrosine kinase activity. rmSCF also had a
      trophic effect on c-kit-positive neurons in the culture of dissociated DRG cells.
      Most c-kit-positive neurons appeared to respond to NGF as well, and the SCF
      responsive subpopulation represented about 10% of NGF-responsive neurons. rmSCF
      did not support the survival of DRG neurons from embryos of W/W and W42/W42
      genotypes. These results suggest that the stimulus through the c-kit receptor
      tyrosine kinase has an important role in development of the peripheral nervous
      system.

PMID- 7506141
TI  - Nimesulide: a multifactorial therapeutic approach to the inflammatory process? A
      7-year clinical experience. Proceedings of an international congress, Berlin,
      October 1-3, 1992.

PMID- 7506142
TI  - The role of interleukins and nitric oxide in the mediation of inflammatory pain
      and its control by peripheral analgesics.
AB  - Tissue injury or the presence of foreign material initiates a series of
      pathophysiological events that may manifest as inflammatory pain. The
      physicochemical characteristics of the initiating factor trigger the release of a
      unique range of pain mediators that control the threshold and activation of
      nociceptors. It has been suggested that many nociceptors associated with
      inflammatory pain are dormant, and are activated by cyclo-oxygenase metabolites
      and sympathomimetic amines into a state of hyperalgesia. In this state, pain
      receptors may be activated by previously ineffective stimuli. The relative
      contribution of the mediators to the activation process varies with the
      experimental model or the pathophysiological process involved. The mechanisms
      that control the activity of the pain receptor are unfolding. Indeed, research
      has shown a central role for bradykinin (released from plasma) and cytokines
      (released from tissues and resident cells) in this process. The release of tumour
      necrosis factor-alpha (TNF-alpha) initiates the release of interleukin-1 and
      interleukin-8, which in turn liberate cyclo-oxygenase metabolites and
      sympathomimetic amines, respectively. In some models of inflammatory pain,
      bradykinin causes hyperalgesia via release of TNF-alpha. Drugs blocking cyclo
      oxygenase (aspirin-like drugs), or those antagonising the effects of
      sympathomimetic amines (beta-blockers), prevent sensitisation of the pain
      receptors. However, during hyperalgesia only specific types of analgesics are
      capable of nociceptor downregulation. It is assumed that sensitisation of
      nociceptors is due to increased concentrations of cAMP/Ca++ in the sensory
      neurons. The effect of increased cAMP concentrations may be counteracted by
      stimulation of the arginine/nitric oxide/cGMP pathway. Peripherally acting
      opiates and dipyrone are examples of analgesics that act via this mechanism. The
      analgesic effects of glucocorticoids and nimesulide appear to be attributable to
      inhibition of cytokine release.

PMID- 7506143
TI  - The effect of nimesulide on prostanoid formation.
AB  - Nimesulide (4-nitro-2-phenoxy-methansulfonanilide) is a weak acidic (pKa = 6.50)
      nonsteroidal anti-inflammatory drug (NSAID) belonging to a new chemical class,
      the sulfonanilide derivatives, and does not contain the carboxylic group. It
      exhibits potent anti-inflammatory, analgesic and antipyretic activities. Although
      nimesulide is not a cyclo-oxygenase inhibitor in gastric tissues or bovine
      seminal vesicle microsomes, it inhibits prostaglandin synthesis in zymosan
      stimulated murine macrophages in inflammatory exudate. Nimesulide significantly
      antagonises the immune formation of thromboxane B2 in lung tissue. It neither
      induces gastrointestinal lesions nor affects renal function in animal models.

PMID- 7506144
TI  - Double-blind study of nimesulide in divers with inflammatory disorders of the
      ear, nose and throat.
AB  - 200 divers of either sex, aged 18 to 54 years, entered a double-blind study to
      compare the efficacy and tolerability of nimesulide 200 mg/day with those of
      seaprose S 60 mg/day in the treatment of nonbacterial inflammatory disorders of
      the ear, nose, and throat. At the end of the 1-week treatment period, both drugs
      were judged to be effective, with improvements and, in most cases, complete
      remission of all symptoms observed. Nimesulide showed greater clinical efficacy,
      and both drugs were well tolerated.

PMID- 7506145
TI  - Nimesulide granules for the treatment of acute inflammation of the ear, nose or
      throat.
AB  - The efficacy of nimesulide (100mg twice daily) was compared with that of naproxen
      (500mg twice daily) in 53 adult patients with nonbacterial acute inflammation of
      the ear, nose or throat in a double-blind phase III clinical investigation. Both
      drugs were administered orally after meals for a mean duration of 8.7 days. In
      this setting, nimesulide was associated with relief of pain and inflammatory
      signs (exudation and swelling). Indeed, treatment with nimesulide led to clinical
      improvement superior to that obtained with naproxen in terms of both rapidity of
      action and improvement of the symptoms at the end of therapy. Nimesulide therapy
      was also very well tolerated and no patient reported an adverse event. In
      contrast, 2 naproxen-treated patients reported episodic gastralgia of moderate
      intensity.

PMID- 7506146
TI  - Treatment of upper airways inflammation with nimesulide.
AB  - Nimesulide treatment for 7 to 10 days is shown to be effective in controlling the
      inflammatory process in upper airways disorders such as rhinitis, rhinosinusitis,
      rhinopharyngitis and tubaritis, and in middle ear disorder (secretory otitis
      media). A concomitant antibacterial is considered necessary in cases involving
      infection, in order to retain the improvements in mucociliary transport obtained
      with anti-inflammatory treatment. Nimesulide is also shown to be effective when
      given in combination with the mucolytic drug ambroxol.

PMID- 7506147
TI  - Nimesulide in the treatment of chronic bronchitis.
AB  - Hypersecretion of mucus is the main feature of chronic bronchitis and is
      associated with an increased susceptibility to bronchial infections. Although
      airway inflammation is present in patients with chronic bronchitis and is
      recognised as a contributing factor in the development of bronchial hyper
      reactivity and obstruction, the role of anti-inflammatory drugs in the treatment
      of chronic bronchitis has not been established. Nimesulide is a nonsteroidal anti
      inflammatory drug that can modulate the function of neutrophils and block the
      effects of several inflammatory mediators. We found that a 3-week treatment
      course of nimesulide in patients with chronic mucus hypersecretion decreased
      sputum viscosity, thus significantly improving symptoms. The effect of nimesulide
      on the rheological properties of mucus was slower and weaker than that of classic
      mucolytics and was more likely to be related to a reduction in bronchovascular
      permeability. The clinical usefulness of nimesulide in chronic bronchitis
      deserves further investigation.

PMID- 7506149
TI  - Nimesulide does not interfere with airway responsiveness in allergic asthma.
AB  - The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) in asthmatic
      patients is limited by the possibility that these drugs may aggravate asthma by
      increasing the production of leukotrienes. Nimesulide, an NSAID with a weak
      inhibitory activity on prostaglandin synthetase, has been hypothesised to be
      safer than other NSAIDs in asthma. We have recently demonstrated in asthmatics
      who were allergic to the house dust mite that nimesulide neither alters the
      bronchial response to allergen nor aggravates the allergen-induced increase in
      airway responsiveness.

PMID- 7506148
TI  - Efficacy and tolerability of nimesulide in asthmatic patients intolerant to
      aspirin.
AB  - Inflammation of the airways accompanied by eosinophil infiltration appears to
      play a fundamental role in the pathogenesis of bronchial asthma. Therefore, anti
      inflammatory agents (at present corticosteroids, cromoglycate and nedocromil) are
      the first-line treatment for this condition. Nonsteroidal anti-inflammatory drugs
      (NSAIDs), such as aspirin (acetylsalicylic acid) and indomethacin, however, have
      never been used in this setting, mainly for fear of adverse effects (e.g. severe
      obstructive reactions); these can occur, in a consistent number of patients as a
      consequence (according to the most widely accepted theory) of inhibition of
      prostaglandin synthesis. In a double-blind crossover placebo-controlled study
      involving 20 aspirin-sensitive patients with asthma, we found that oral
      nimesulide 100mg was well tolerated both clinically and functionally (no
      significant changes in forced expiratory volume in 1 second and specific airway
      resistance after drug intake). In a more recent study, we observed a mild
      obstructive reaction (easily controlled with inhaled bronchodilators) after oral
      administration of nimesulide 400mg to 3 patients who had previously tolerated a
      100mg dose. On the basis of clinical experience, nimesulide (unlike most other
      NSAIDs) in the recommended doses appears to be well tolerated in aspirin
      sensitive asthmatic patients. Furthermore, this distinctive anti-inflammatory
      agent might provide a novel approach to the treatment of bronchial asthma.

PMID- 7506150
TI  - A comparison of nimesulide vs paracetamol in the treatment of pyrexia in the
      elderly.
AB  - The efficacy and safety of rectally administered nimesulide 200mg and paracetamol
      500mg were assessed in a double-blind study. The study was conducted in 39
      elderly inpatients with infections of the upper or lower respiratory tract
      associated with fever; 18 patients received nimesulide and 21 received
      paracetamol. Both treatments were given for 2 consecutive days and provided
      adequate therapy for pyrexia, with significant reductions in body temperature
      being observed. Both drugs were well tolerated. Only 1 patient in the nimesulide
      treated group could not complete the study because cutaneous erythema occurred
      with itching; this resolved spontaneously upon treatment withdrawal. It is
      concluded that nimesulide is as active and safe as paracetamol for the treatment
      of pyrexia in the elderly.

PMID- 7506151
TI  - Nimesulide in dysmenorrhoea.
AB  - Nimesulide does not affect active intrauterine pressure, as measured using
      microsensors, or the direction and velocity of the propagation of uterine
      activity, but nevertheless alleviates pain significantly by 30 minutes after oral
      administration. In dysmenorrhoeic patients, resting pressure is high only in the
      fundus. Nimesulide reduces the pressure during the maximal but not during the
      submaximal pain period, with concomitant alleviation of pain. The drug changes
      the painful state of uterine contracture to painless cyclic contractions. With a
      single oral dose of 100mg, nimesulide is evenly distributed in female genital
      tissues (uterine fundus and cervix, oviduct and ovaries), reaching peak
      concentrations and peak plasma: tissue ratio (0.5) 3 hours after administration.
      Tissue concentrations range from 0.3 to 1.8 micrograms/g. Two 100mg oral doses of
      nimesulide administered to dysmenorrhoeic women in a double-blind placebo
      controlled cross-over study reduced prostaglandin F2 alpha levels in menstrual
      blood from 382 to 94 micrograms/L. Double-blind placebo-controlled studies also
      confirmed that nimesulide relieves pain in dysmenorrhoeic patients.

PMID- 7506152
TI  - Nimesulide in the treatment of pelvic inflammatory diseases. A multicentre
      clinical trial conducted in Campania and Sicily.
AB  - 400 patients aged 18 to 71 years took part in a multicentre noncomparative study
      designed to assess the clinical efficacy and tolerability of nimesulide in
      gynaecological inflammatory disease: adnexitis (72 patients), cervicitis (78
      patients), endometritis (18 patients), myometritis (22 patients), and combined
      disorders (210 patients). All patients were treated with nimesulide 100mg twice
      daily in granular form for an average of 19.5 days. The treatment produced good
      results in all types of diseases considered, with a significant decrease in
      severity of symptoms being observed. The drug was well tolerated.

PMID- 7506153
TI  - Nimesulide in the treatment of mastalgia.
AB  - Sixty patients with mastalgia, either idiopathic or secondary to dysplastic
      lesions, were treated with oral nimesulide (100mg tablets twice daily) for 15
      days. Breast tension and pain, assessed at baseline and on completion of the
      treatment period, improved or resolved with therapy. Indeed, breast pain (which
      most likely manifests as a consequence of periductal inflammation) was most
      noticeably reduced. The drug was well tolerated in nearly all patients. These
      results support the usefulness of nimesulide and other nonsteroidal anti
      inflammatory drugs in the treatment of mastalgia.

PMID- 7506154
TI  - Nimesulide in the treatment of menstrual migraine.
AB  - In a controlled double-blind clinical trial, 30 patients aged 18 to 45 years,
      with menstrual migraine, were randomly assigned to 2 parallel treatment groups of
      15 patients each. One group received granular nimesulide 100mg 3 times daily and
      the other group received placebo. Each treatment was given for 10 days, starting
      from the onset of migraine symptoms, and was repeated for the 2 following
      menstrual cycles. The overall assessment of efficacy in the 2 groups was based on
      hourly self-evaluation of pain during each study day. In patients treated with
      nimesulide, pain intensity and duration were significantly reduced compared with
      placebo (p = 0.0001) during all the menstrual cycles in the study.

PMID- 7506155
TI  - Controlled clinical studies of nimesulide in the treatment of urogenital
      inflammation.
AB  - Two double-blind, randomised studies were conducted to compare the efficacy and
      tolerability of nimesulide (200 mg/day) with those of placebo or bromeline (240
      mg/day). Treatments were administered orally to patients of either sex (aged 19
      to 70 years) with acute infection and inflammation of the urogenital tract, and
      were given concomitantly with antimicrobial therapy for approximately 9 days. In
      both studies, a clinically significant improvement in symptoms, leading to
      complete remission, was achieved in most patients treated with nimesulide.
      Furthermore, treatment with nimesulide resulted in a more rapid improvement in
      symptoms and complete remission in a greater number of patients than did
      treatment with bromeline. Both nimesulide and bromeline were well tolerated.

PMID- 7506156
TI  - Treatment of abacterial prostato-vesiculitis with nimesulide.
AB  - The efficacy and tolerability of nimesulide were assessed in the treatment of
      patients with prostato-vesiculitis. In a noncomparative investigation, 30
      patients received oral nimesulide 100mg twice daily for three 10-day cycles.
      Micturition-related symptoms were resolved in 20 patients and clear amelioration
      of inflammatory signs was observed with transrectal ultrasound in 16 patients.
      Abnormal sperm forms decreased from 57 to 49% (p < 0.001). In a comparative
      investigation, 40 patients received nimesulide 200mg twice daily or ketoprofen
      100mg twice daily via the rectal route. Patients and physicians expressed an
      overall opinion on efficacy in favour of nimesulide. In a pharmacokinetic study
      of healthy volunteers who received oral nimesulide 100mg as a single dose, the
      mean maximum nimesulide concentration (0.58 +/- 0.13 mg/L) in seminal fluid was
      achieved after 2 hours while the maximum seminal fluid: blood plasma ratio 0.32
      +/- 0.02 was observed after 4 hours. These data suggest that nimesulide is an
      effective NSAID in the treatment of abacterial prostato-vesiculitis and also
      demonstrate that this drug has a favourable disposition within the genital tract.

PMID- 7506157
TI  - Antioxidant activity of nimesulide and its main metabolites.
AB  - The antioxidant activity of nimesulide and its main metabolites, 4'
      hydroxynimesulide (M1) and 2-(4'-hydroxyphenoxy)-4-N-acetylamino
      methansulfonanilide (M2), was investigated using 2 in vitro models: NADPH
      supported lipid peroxidation in rat liver microsomes (marker MDA formation) and
      xanthine/xanthine oxidase, iron-promoted depolymerisation of hyaluronic acid,
      determined by gel permeation chromatographic analysis (marker molecular weight
      distribution). In the lipid peroxidation model, all the compounds inhibited MDA
      formation in a concentration-dependent manner, although with different potencies;
      the maximum scavenging effect was observed for M1 [50% inhibitory concentration
      (IC50) = 30 mumol/L; M2 IC50 = 0.5 mmol/L; nimesulide = 0.8 mmol/L]. Nimesulide
      was more active than its metabolites in preventing OH-induced depolymerisation of
      hyaluronic acid, with a 50% effective concentration of approximately 230 mumol/L,
      which was fairly comparable to that of tenoxicam. This protective effect was due
      to the OH.-entrapping capacity of the drug, which, in the Fenton-driven model, is
      easily converted, via OH. attack, to M1 and putatively to 2-hydroxy-4-nitro
      methansulfonanilide.

PMID- 7506158
TI  - Nimesulide and diclofenac in the control of cancer-related pain. Comparison
      between oral and rectal administration.
AB  - 64 patients with pain associated with advanced cancer were treated with either
      nimesulide or diclofenac as initial analgesia. Patients were randomly allocated
      to 1 of 4 treatment groups: oral nimesulide 300 mg/day; oral diclofenac 150
      mg/day; rectal nimesulide 400 mg/day; and rectal diclofenac 200 mg/day. After 1
      week of treatment, both drugs provided an adequate degree of pain relief and
      allowed an increase in sleep duration. There were no significant differences in
      efficacy between the drugs or routes of administration. Fewer side effects were
      observed with nimesulide, giving this agent a better therapeutic index than the
      reference compound.

PMID- 7506159
TI  - Nimesulide in the treatment of advanced cancer pain. Double-blind comparison with
      naproxen.
AB  - The analgesic efficacy and tolerability of nimesulide and naproxen were compared
      in 68 patients with advanced cancer who needed to be treated with nonsteroidal
      anti-inflammatory drugs according to the first step of the pharmacological
      analgesic scale of the WHO. Patients received either nimesulide 200mg or naproxen
      500mg twice daily. The analgesic efficacy and tolerability of the 2 drugs
      appeared to be similar. Both drugs were effective and were associated with a low
      incidence of adverse reactions.

PMID- 7506160
TI  - Comparison of nimesulide and diclofenac in the prevention and treatment of
      painful inflammatory postoperative complications of general surgery.
AB  - In a double-blind study, 40 patients scheduled for saphenectomy or inguinal
      hernioplasty were randomly assigned to treatment with nimesulide (200mg 3 times
      daily) or diclofenac (100mg 3 times daily) administered rectally. Therapy with
      either drug resulted in significantly less pain, oedema and hyperaemia, and
      resolution of mild fever. No adverse reactions attributable to treatment were
      observed.

PMID- 7506161
TI  - Controlled clinical investigation of acute analgesic activity of nimesulide in
      pain after oral surgery.
AB  - A double-blind study was conducted to determine the dose-effect relationship of
      nimesulide and to compare the acute analgesic activity of this agent with that of
      placebo and niflumic acid. Patients undergoing extraction of an impacted third
      molar were randomised into 4 groups (nimesulide 100mg; nimesulide 200mg; niflumic
      acid 250mg and placebo). They were instructed to take their allocated treatment
      after the onset of pain, and to record the pain severity and relief during the
      following 6 hours. 134 patients were evaluated. There were significant
      differences between groups for each time of observation/efficacy parameter
      (Kruskal-Wallis test). Pairwise comparison (Duncan's test) showed that all 3
      active medications were significantly different from the placebo. No substantial
      differences were found between any of the active treatments. Analogous results
      were obtained when the amount of rescue drug used (paracetamol) was compared.
      More positive judgements were reported by patients treated with an active
      compound than by those taking placebo.

PMID- 7506162
TI  - A double-blind comparison of nimesulide and ketoprofen in dental surgery.
AB  - The efficacy and tolerability of nimesulide were compared with those of
      ketoprofen when administered rectally in a double-blind investigation of 46
      patients scheduled for dental surgery. Nimesulide was more effective and more
      rapid than ketoprofen in ameliorating the painful inflammatory symptoms (pain at
      rest and upon mastication) and signs (swelling and hyperaemia) associated with
      the operation. These effects were accompanied by improved quality of sleep and
      recovery of masticatory and swallowing function, which was superior for
      nimesulide-treated patients.

PMID- 7506163
TI  - A controlled clinical study of the efficacy and tolerability of nimesulide vs
      naproxen in maxillo-facial surgery.
AB  - The anti-inflammatory and analgesic efficacy of nimesulide was assessed and
      compared with that of naproxen in the postoperative treatment of inflammatory
      complications of maxillo-facial surgery in a double-blind study. A total of 60
      patients were randomly assigned to treatment with nimesulide (100mg twice daily)
      or naproxen (250mg twice daily) for 6 to 14 days. Treatment with either drug
      prevented the development of, or ameliorated the signs and symptoms associated
      with, the inflammatory process (spontaneous pain, difficulty in chewing and
      swallowing, swelling, hyperaemia, muscle contracture, poor sleep quality).
      Indeed, most patients experienced complete resolution of their signs and
      symptoms. The efficacy of nimesulide was considered to be superior to that of
      naproxen, although both drugs were tolerated equally well.

PMID- 7506164
TI  - A comparison of nimesulide and ketoprofen in the prevention and treatment of
      painful postoperative inflammatory complications of ear, nose and throat surgery.
AB  - In a randomised double-blind clinical study, 76 patients undergoing major ear,
      nose or throat (ENT) surgery (including 45 for cancer) were treated with
      nimesulide (200mg twice daily) or ketoprofen (100mg twice daily) administered
      rectally for 5 days. Pain intensity was significantly and similarly reduced in
      both treatment groups compared with baseline (p = 0.0001). A significant
      reduction in oedema and hyperaemia was observed on the second day for nimesulide
      treated patients and on the third day for those treated with ketoprofen, with
      complete relief being noted for almost all patients by the fifth day. Fever was
      resolved in all patients. Adverse events attributable to treatment were observed
      for 1 patient in each group. These results suggest that nimesulide provides a
      worthwhile alternative to other NSAIDs in the treatment of postoperative pain and
      inflammation associated with ENT surgery.

PMID- 7506165
TI  - Clinical efficacy and tolerability of nimesulide compared with naproxen in the
      treatment of posthaemorrhoidectomy pain and inflammation.
AB  - The efficacy and tolerability of nimesulide and naproxen were compared in a
      randomised double-blind study of patients with pain and inflammation after
      haemorrhoidectomy. Both drugs appeared similarly effective in reducing pain and
      oedema and no adverse reaction was detected. These data extend the information on
      the anti-inflammatory and analgesic efficacy of nimesulide in the postoperative
      setting.

PMID- 7506166
TI  - Efficacy of nimesulide in the prevention of inflammatory complications after
      laser treatment of ocular diseases.
AB  - A total of 40 patients with various ocular diseases were treated with nimesulide
      200 mg/day or ketoprofen 150 mg/day for 7 days after laser therapy. The incidence
      of ocular complications was lower in patients treated with nimesulide than with
      ketoprofen. With regard to posterior segment changes, retinal oedema was reduced
      in patients treated with nimesulide. After laser treatment, anterior segment
      changes were modest. These preliminary results stress the efficacy of nimesulide
      in preventing oedema and also its anti-inflammatory effects on the retina after
      ocular laser therapy.

PMID- 7506167
TI  - A double-blind study of the efficacy of nimesulide in the treatment of ankle
      sprain in comparison with placebo.
AB  - In a randomised double-blind study, nimesulide 100mg twice daily for 8 days was
      compared with placebo in the treatment of 60 patients with ankle sprain. On day
      4, three nimesulide-treated patients discontinued treatment because of resolution
      of their symptoms, whereas 11 patients in the placebo group discontinued as a
      result of worsening symptoms. A significantly greater reduction in pain,
      functional impairment and swelling was observed with nimesulide compared with
      placebo; moreover, the time to improvement was significantly shorter with the
      active treatment. The overall evaluation of efficacy favoured nimesulide over
      placebo (p < 0.001). Both medications were well tolerated, with 5 patients
      reporting mild gastralgia (4 treated with nimesulide and 1 with placebo), while 1
      placebo-treated patient reported a mild gastrointestinal disturbance. These
      results suggest that nimesulide is an effective treatment for the short term
      management of post-traumatic pain states.

PMID- 7506168
TI  - A multicentre double-blind investigation comparing nimesulide and naproxen in the
      treatment of minor sport injuries.
AB  - A total of 660 patients with minor traumatic sport-related lesions of soft
      tissues were recruited to a randomised double-blind 7-day study to evaluate the
      efficacy and the tolerability of oral nimesulide (300 mg/day) in comparison with
      naproxen (750 mg/day). Both drugs were similarly effective in reducing the degree
      of oedema and intensity of pain, with most patients experiencing remission, which
      allowed resumption of regular sporting activities. Both drugs were generally well
      tolerated, although gastrointestinal intolerance was more frequently associated
      with naproxen therapy.

PMID- 7506169
TI  - Nimesulide in the treatment of osteoarthritis. Double-blind studies in comparison
      with piroxicam, ketoprofen and placebo.
AB  - The efficacy and tolerability profiles of nimesulide (a nonsteroidal anti
      inflammatory drug) were assessed in 3 comparative double-blind clinical trials
      that each recruited 60 patients with osteoarthritis of the hip or knee. The
      duration of each investigation varied with the comparator agent chosen: 2 weeks
      for placebo; 3 weeks for piroxicam; 2 months for ketoprofen. Nimesulide and
      ketoprofen were each administered orally as a 100mg dose twice daily, while
      piroxicam was administered orally as a single daily 20mg dose. In each study the
      principal efficacy parameters were the improvement in spontaneous pain, assessed
      using a visual analogue scale, and the degree of functional impairment evaluated
      using the severity index of Lequesne; the final judgement of efficacy was made by
      the physician. In all studies, nimesulide improved these and other efficacy
      parameters with an activity significantly superior to that of placebo and
      comparable with that of reference drugs.

PMID- 7506170
TI  - A comparison of nimesulide and diclofenac in the treatment of acute superficial
      thrombophlebitis.
AB  - In a double-blind study, the efficacy and tolerability of nimesulide (100mg twice
      daily) were compared with those of diclofenac (50mg twice daily) when
      administered orally to 50 patients with acute superficial thrombophlebitis of the
      lower limbs. Pain relief and amelioration of inflammation were apparent in
      patients treated with either nimesulide or diclofenac; however, gastric
      intolerance was noted more frequently in those receiving diclofenac. The results
      of this study suggest that nimesulide should be considered as an alternative to
      diclofenac and other first-line NSAIDs in the treatment of acute superficial
      thrombophlebitis.

PMID- 7506171
TI  - Double-blind comparison of nimesulide and diclofenac in the treatment of
      superficial thrombophlebitis with telethermographic assessment.
AB  - A total of 60 patients with acute varicophlebitis or acute superficial
      thrombophlebitis of the lower limbs were recruited to this randomised double
      blind comparative study, which evaluated the efficacy and tolerability of oral
      nimesulide (100mg twice daily) with those of diclofenac (50 mg/kg twice daily)
      over a period of < or = 20 days (average duration 13.6 days for nimesulide and
      12.6 days for diclofenac). The analgesic effect of both drugs was rapid.
      Spontaneous pain disappeared within 3 to 5 days of commencing therapy, and pain
      on palpation within 7 days. Reduced inflammation was observed after approximately
      15 days, and total resolution of redness and swelling was observed by day 20.
      Telethermographic assessment showed a reduction in local temperature, either in
      absolute terms or in the extent of inflammation. Indeed, 93% of patients showed
      complete recovery while 7% of patients showed a partial reduction in
      hyperthermia. For these latter patients, medical treatment was extended, although
      the subjective symptoms of the disease were no longer present. The comparison
      between nimesulide and the reference drug, diclofenac sodium, showed no
      significant difference for any of the considered parameters. Both drugs were well
      tolerated and no patient reported an adverse event.

PMID- 7506172
TI  - Antipyretic and anti-inflammatory efficacy of nimesulide vs paracetamol in the
      symptomatic treatment of acute respiratory infections in children.
AB  - To evaluate the clinical efficacy of nimesulide vs paracetamol in the treatment
      of acute inflammatory disorders of the airways, 40 paediatric patients (aged 3 to
      12 years) with acute viral infections of the lower respiratory tract not
      requiring systemic antibiotic therapy in the first 3 days of observation were
      studied. Patients were randomly divided into 2 homogeneous groups receiving
      either oral nimesulide 1.5 mg/kg/day 3 times daily or paracetamol 120 to 288mg (5
      to 12ml) 3 times daily for 3 to 7 days. Standard laboratory tests and chest x
      rays were obtained at the beginning and end of treatment, and body temperature,
      blood arterial pressure and heart rate were recorded regularly. The anti
      inflammatory effects of the 2 drugs (based on normalisation of erythrocyte
      sedimentation rate, C-reactive protein values, and white blood cell counts) were
      evaluated and the overall duration of the disease was assessed. The results
      showed that nimesulide was more effective than paracetamol in normalising body
      temperature (p < 0.05) and in reducing the inflammatory indices (p < 0.05), and
      that patients in the nimesulide group required a shorter treatment period than
      patients in the paracetamol group. No abnormal changes in arterial blood pressure
      or blood and urine analyses were seen in either group, and the reduction in heart
      rate was similar in both groups.

PMID- 7506173
TI  - A double-blind comparison of nimesulide and mefenamic acid in the treatment of
      acute upper respiratory tract infections in children.
AB  - The efficacy and safety of nimesulide suspension were evaluated in comparison
      with mefenamic acid in a double-blind multicentre study that recruited 100
      children with acute respiratory tract infections. On entry, each child was
      randomly allocated to receive either nimesulide 5 mg/kg/day or mefenamic acid 5
      mg/kg divided into 2 or 3 daily doses as an oral suspension, for a period of 3 to
      10 days. Body temperature returned to normal on the third day for most of the
      nimesulide-treated patients, but only on the fifth day for the mefenamic acid
      group. There was a significant difference (p < 0.01) between the antipyretic
      activity of nimesulide and that of mefenamic acid. Furthermore, treatment with
      nimesulide was associated with clinically significant improvement in all
      inflammatory signs and symptoms observed (rhinorrhoea, nasal obstruction,
      pharyngeal redness, swelling of lymph nodes and cough). Adverse effects
      considered possibly related to treatment were recorded for 3 patients treated
      with nimesulide and 1 with mefenamic acid.

PMID- 7506174
TI  - A comparison of nimesulide and placebo in the treatment of minor traumatic soft
      tissue lesions in children.
AB  - A total of 40 children with minor traumatic injuries of soft tissues were
      randomly assigned to oral treatment with nimesulide (50mg twice daily) or placebo
      for 5 days in a double-blind investigation. Results demonstrated that therapy
      with nimesulide was associated with a significant resolution of symptoms (pain at
      rest and during movement) and signs (oedema, immobility and haematoma), which was
      statistically superior to that demonstrated for placebo. Furthermore, nimesulide
      was well tolerated by all patients and was not associated with gastrointestinal
      problems. These findings suggest that nimesulide is a suitable therapy for
      children with minor traumatic lesions.

PMID- 7506175
TI  - Clinical and pharmacokinetic study of nimesulide in children.
AB  - The pharmacokinetic profile and efficacy of nimesulide were assessed in 2
      separate studies that recruited children with hypoglycaemia or upper respiratory
      tract infection and fever, respectively. A single dose of nimesulide 50mg
      (granules) administered orally to 14 hypoglycaemic children was rapidly absorbed.
      A mean maximum nimesulide plasma concentration of 3.5 mg/L was achieved within 2
      hours of administration, which subsequently declined over the following 12 hours.
      Nimesulide was metabolised to its principal hydroxy metabolite, which was
      detectable in samples obtained 0.5 hours after giving the parent drug. Levels of
      this metabolite steadily increased, surpassing those of intact nimesulide at the
      9-hour sampling point. In a randomised nonblind clinical investigation, 100
      hospitalised children with acute upper respiratory infections and fever received
      nimesulide oral suspension (5 mg/kg/day) or paracetamol (26 mg/kg/day) for 3 to 9
      days. The antipyretic and anti-inflammatory effects of nimesulide were superior
      to those observed with paracetamol (p < 0.01) and both drugs were equally well
      tolerated.

PMID- 7506176
TI  - Double-blind evaluation of nimesulide vs lysine-aspirin in the treatment of
      paediatric acute respiratory tract infections.
AB  - 70 children aged 4 to 12 years with acute infection and inflammation of the
      respiratory tract (laryngitis, tracheitis, bronchitis, pneumonia) were enrolled
      in a double-blind investigation and randomised to treatment with nimesulide (50mg
      granules twice daily) or lysine-aspirin (360mg granules twice daily) for 5 days.
      The drugs were similarly effective in reducing cough, asthenia and dyspnoea,
      although nimesulide-treated patients experienced fewer gastrointestinal adverse
      events. These results confirm the efficacy of nimesulide in the treatment of
      respiratory inflammation and provide preliminary evidence of its value in
      children.

PMID- 7506177
TI  - New data concerning the antianaphylactic and antihistaminic activity of
      nimesulide.
AB  - The time to respiratory crisis in ovalbumin-sensitised guinea-pigs following
      exposure to aerosol administered antigen was dose dependently delayed by
      inhalation of nimesulide (0.1% to 1%), whereas indomethacin had no effect. At the
      same time, nimesulide significantly reduced blood histamine concentrations, in
      contrast to the slight increase observed with indomethacin. In human bronchial
      muscle preparations, nimesulide, but not indomethacin, antagonised H1-histamine
      receptor activation by histamine and was without effect on acetylcholine-induced
      responses. Bronchoconstriction was also elicited in anaesthetised guinea-pigs by
      intravenous acetaldehyde (5% in saline, 1 ml/kg). This effect, which is
      paralleled by a rise in blood histamine concentrations, was significantly
      attenuated by inhaled nimesulide (0.1% to 1%), but not by indomethacin (1%).
      These data, which further support the antihistaminic and antiallergic activity of
      nimesulide, may have therapeutic relevance in patients who are affected by
      inflammation of the respiratory tract and who also have a history of allergic
      bronchoconstriction.

PMID- 7506178
TI  - Efficacy and tolerability of nimesulide and lysine-acetylsalicylate in the
      treatment of paediatric acute upper respiratory tract inflammation.
AB  - In a single-blind study that recruited 70 children aged 5 to 12 years with acute
      upper respiratory tract infection and fever (in- or outpatients), the
      effectiveness and tolerability of nimesulide 50 mg/dose were compared with those
      of lysine-acetylsalicylate 720 mg/dose (equivalent to 200mg of salicylate). Each
      agent was administered to 35 children, and both groups were simultaneously
      treated with antibiotics. General and respiratory symptoms were evaluated daily.
      Nimesulide treatment was associated with a more rapid and greater antipyretic
      effect than lysine-acetylsalicylate: 94% of nimesulide recipients and 77% of
      lysine-acetylsalicylate recipients were considered by physicians to have a good
      or very good response to therapy (p < 0.05). Furthermore, fewer doses of
      nimesulide than lysine-acetylsalicylate were required for resolution of fever and
      associated symptoms (nausea, vomiting, headache). The 2 drugs had similar global
      efficacy. Tolerability was good or very good in all patients.

PMID- 7506179
TI  - Assessment of the efficacy and safety of nimesulide vs naproxen in paediatric
      patients with respiratory tract infections. A comparative single-blind study.
AB  - A total of 99 paediatric patients (57 male, 42 female) aged 1 to 12 years,
      weighing 10 to 40kg and with acute pharyngo-amygdalitis were enrolled in a single
      blind study to assess the efficacy and tolerability of nimesulide in comparison
      with naproxen when both drugs were administered over an 8-day treatment period.
      Among the 2 treatment groups comprising 99 evaluable patients, demographic
      analysis of age, weight and height did not reveal statistically significant
      differences. Evaluation of fever, pain, inflammation and nasal obstruction over
      the 8-day treatment period showed a significant improvement in these parameters
      for those patients treated with nimesulide when compared with naproxen from day
      1, with remission of symptoms starting from day 3. These findings were
      complemented by a superior tolerability profile reported for nimesulide-treated
      patients. In conclusion, nimesulide appears to be a safe and effective treatment
      for paediatric patients with pharyngo-amygdalitis and it has shown superior
      efficacy and tolerability when compared with naproxen.

PMID- 7506180
TI  - A comparison of nimesulide and paracetamol in the treatment of fever due to
      inflammatory diseases of the upper respiratory tract in children.
AB  - The efficacy and tolerability of nimesulide were compared with those of
      paracetamol in a nonblind randomised study that recruited 110 children (64 males,
      46 females; aged 3 to 6 years) with inflammation of the upper respiratory tract
      and fever. Nimesulide suspension (1.5 mg/kg 3 times daily) or paracetamol syrup
      (10 mg/kg 4 times daily) were administered orally until fever resolved. Body
      temperature was recorded and local pain and general discomfort assessed. Three
      patients treated with nimesulide and 6 patients treated with paracetamol withdrew
      from the study as a result of adverse events, and 1 paracetamol-treated patient
      discontinued because of a requirement for therapy with steroids. Nimesulide was
      as effective as paracetamol in reducing fever, local pain, and general
      discomfort. Nimesulide therefore appears to be at least as effective as
      paracetamol in terms of antipyretic and anti-inflammatory activity in children
      with inflammation of the upper respiratory tract and fever.

PMID- 7506182
TI  - Tolerability of nimesulide and ketoprofen in paediatric patients with traumatic
      or surgical fractures.
AB  - The anti-inflammatory and analgesic activities of orally administered nimesulide
      and ketoprofen were assessed in a group of 71 paediatric patients (aged 7 to 14
      years) with orthopaedic disorders. Both drugs had similar efficacy. The greatest
      advantage of nimesulide was its better tolerability: only 3 nimesulide-treated
      patients (8.6%) experienced side effects related to the drug, compared with 12
      (33%) of the ketoprofen-treated children.

PMID- 7506181
TI  - An assessment of the efficacy and tolerability of nimesulide vs paracetamol in
      children after adenotonsillectomy.
AB  - The efficacy and tolerability of nimesulide were assessed and compared with those
      of paracetamol in the treatment of 35 children with pain and inflammation
      following adenotonsillectomy. The antipyretic and analgesic efficacy of the 2
      drugs was similar, although more patients had complete remission of pain after 4
      days of treatment with nimesulide. Both drugs were well tolerated, even though
      occasional elevation of transaminase enzymes and alkaline phosphatase was noted
      in the nimesulide-treated group. It is postulated that this effect may have been
      attributable to the volatile anaesthetics used during surgery.

PMID- 7506183
TI  - Toxicity of nonsteroidal anti-inflammatory drugs. An overview of the
      epidemiological evidence.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the
      world. This paper reviews the epidemiological data linking NSAID administration
      with gastrointestinal, hepatic, renal, haematological, and hypersensitivity
      reactions. Meta-analysis has demonstrated that NSAIDs are associated with serious
      upper gastrointestinal disorders, with a relative risk of 2.7 in patients
      receiving NSAIDs compared with subjects not receiving NSAIDs. An increase in the
      dose and duration of NSAIDs and age > 60 are associated with an increase in the
      risk of upper gastrointestinal toxicity. The current data strongly support a
      causal relationship between NSAIDs and gastrointestinal disorders. Case-control
      studies have demonstrated an association between some NSAIDs and neutropenia,
      with a relative risk of between 3 and 9 in patients treated with NSAIDs compared
      with nonusers of these drugs. NSAIDs have also been linked with hypersensitivity
      reactions, although the incidence of such reactions is very low. However, there
      are inconsistent data on the potential associations between NSAIDs and renal
      disease, and there are no epidemiological studies linking NSAIDs with acute liver
      disease. Overall, the incidence of serious adverse reactions associated with
      NSAIDs is low, and this class of drugs can be regarded as being reasonably safe.

PMID- 7506185
TI  - Oral challenge with alternative nonsteroidal antiinflammatory drugs (NSAIDs) and
      paracetamol in patients intolerant to these agents.
AB  - The reliability and safety of the oral challenge procedure were evaluated in the
      diagnosis and prevention of intolerance to nonsteroidal anti-inflammatory drugs
      (NSAIDs). 112 NSAID-intolerant patients were submitted to oral challenge with
      aspirin (acetylsalicylic acid), dipyrone, paracetamol, imidazole-hydroxybenzoate
      or nimesulide to confirm historic intolerance and to evaluate tolerance to other
      NSAIDs. A significant correlation was demonstrated between history of intolerance
      and the results of oral challenge in aspirin-intolerant patients (p < 0.001). Of
      237 challenges with various NSAIDs and paracetamol in 101 patients, 19 challenges
      were positive and 2 patients developed anaphylactic shock. The ratio of positive:
      total challenges with alternative NSAIDs and paracetamol were as follows: 7 of 83
      for paracetamol, 2 of 49 for imidazole-hydroxybenzoate and 0 of 30 for
      nimesulide. On the basis of these results, nimesulide was evaluated as an
      alternative NSAID in a second group of 284 NSAID-intolerant patients. Challenge
      with nimesulide elicited a positive response in 14 patients (in 6 patients the
      response was delayed), although adverse reactions were mild in all instances. In
      conclusion, a positive history of intolerance to a given NSAID is a sufficient
      reason to contraindicate its use even for diagnostic purposes, e.g. oral
      challenge. Oral challenge should therefore be restricted to the assessment of the
      tolerability of alternative NSAIDs. In the present study nimesulide appeared to
      be the safest currently available alternative in patients with NSAID intolerance.

PMID- 7506184
TI  - Gastric tolerability of nimesulide. A double-blind comparison of 2 oral dosage
      regimens and placebo.
AB  - This double-blind parallel-group study aimed to evaluate, by endoscopic
      examination, the reaction of the gastric mucosa to 7-day oral administration of
      nimesulide 100 or 200mg twice daily. Placebo was administered as a reference
      compound. 30 dyspeptic patients, randomly allocated to 1 of the 3 treatment
      groups, completed the study. On completion of treatment, 1 patient in each
      nimesulide dosage group and 2 in the control group showed evidence of gastric
      injury: 1 patient with slight hyperaemic gastropathy at baseline developed
      superficial ulcerations after treatment with nimesulide 100mg, and 1 patient with
      a history of gastric ulcer developed a congested corpus mucosa with several
      erosions and ulcerations after treatment with nimesulide 200mg; in the placebo
      group, 1 patient developed hyperaemic antropathy and another patient developed
      several petechiae and microerosions. The incidence of adverse effects was
      comparable in all groups and treatment was not associated with any significant
      modification of the considered haematological and haematochemical parameters.

PMID- 7506186
TI  - Renal effects of nimesulide in furosemide-treated subjects.
AB  - In clinical settings where effective plasma volume is decreased, nonsteroidal
      anti-inflammatory drugs (NSAIDs) may induce acute renal failure. We have
      evaluated the effects of single and repeated doses of nimesulide on renal
      haemodynamics and electrolyte excretion in 8 healthy volunteers during a
      prolonged course of furosemide (frusemide). Under these study conditions, renal
      prostaglandin synthesis is expected to be elevated, with renal function being
      dependent upon increased levels of prostaglandins. Nimesulide induced an acute
      but transient decrease in indices of renal haemodynamics. Furosemide-induced
      increases in plasma renin activity and aldosterone levels were blunted, and
      urinary excretion of prostaglandin E2 was markedly reduced by nimesulide. The
      magnitude and time course of the natriuretic, kaliuretic and diuretic effects of
      furosemide were attenuated by nimesulide. Although the transient nature of the
      observed renal haemodynamic changes suggests that the risk of developing acute
      renal failure is small, the rise should be taken into account in patients with
      renal dysfunction. Sodium and potassium retention, and the blunting of the
      diuretic-induced electrolyte excretion, could be of clinical relevance.
      Nimesulide appears, therefore, to share the prostaglandin-dependent renal effects
      of other NSAIDs.

PMID- 7506188
TI  - Long term tolerability profile of nimesulide in the treatment of osteoarthritis.
AB  - As a primary objective, the safety profile of nimesulide was assessed in a
      nonblinded study that recruited 134 patients (aged 41 to 82 years) with
      osteoarthritis requiring long term treatment (> or = 1 year). Nimesulide (100mg
      orally twice daily) was well tolerated. No statistically significant differences
      were found between the number of patients of varying ages reporting adverse
      events. Moreover, most adverse experiences were found to be mild to moderate in
      intensity, with a prevalence of gastrointestinal disorders. The number of adverse
      episodes reported steadily decreased over the duration of the trial and no
      pathological changes in haematology and blood chemistry tests were found.
      Evaluation of efficacy revealed a progressive reduction in pain intensity with
      time.

PMID- 7506187
TI  - Renal and general tolerability of repeated doses of nimesulide in normal
      subjects.
AB  - The renal and general tolerability of nimesulide was studied in 16 healthy men,
      randomised to 4 groups of 4 subjects. The groups all underwent 2 treatment
      periods of 7 days each, separated by a washout period of 14 days. The second
      treatment period was always at a higher dosage level than the first. There were 4
      dosage regimens: placebo, and nimesulide 200, 300 and 400mg, all given twice
      daily by mouth according to a double-blind design. The tolerability of nimesulide
      was assessed by regular clinical examination, nondirected questions about adverse
      events, haematological and biochemical screening, and daily urine testing. Plasma
      and urinary concentrations of Tamm-Horsfall glycoprotein (THG), urinary retinol
      binding protein (RBP) and beta-N-acetyl glucosaminidase (NAG) on days 1, 3, 7,
      and 10 of each period were used as selective indicators of nephrotoxicity. The
      highest dose of nimesulide (800mg daily) was associated with abdominal pain and
      indigestion in 5 of 8 recipients. The 400 and 600mg daily dosages were well
      tolerated. There were no clinically significant alterations in the haematological
      or biochemical screening tests during the study, and daily urinalysis remained
      normal throughout. The renal toxicity tests showed no evidence of nephrotoxicity
      associated with the administration of nimesulide in 14 subjects. The other 2
      subjects each had modest increases in either urinary THG or NAG concentrations
      during treatment with nimesulide 800mg daily, but the results of their other
      tests remained normal. The study, therefore, showed only equivocal evidence of
      minor renal toxicity with nimesulide 800mg daily. Nimesulide 400 and 600mg daily
      were well tolerated in all respects, even though these dosages are higher than
      those recommended for clinical use.

PMID- 7506189
TI  - Nimesulide. New clinical opportunities.

PMID- 7506190
TI  - Tolerability of nimesulide. Epidemiological data.
AB  - This review describes the tolerability profile of nimesulide as documented in a
      global assessment of the clinical data available to Helsinn for this drug. Data
      from 151 trials were considered and the relevant case report forms and study
      reports were used as source information. The analysis was conducted using between
      treatment and within-treatment comparisons. The between-treatment comparison
      included data derived from placebo-controlled trials, while the within-treatment
      comparison included nimesulide data only. Of 4945 subjects treated with
      nimesulide, 349 (7.1%) experienced adverse events and 52 (1.1%) withdrew from
      treatment. The most frequently reported adverse events were those related to the
      digestive system, body as a whole, skin and nervous system. The incidence and
      nature of adverse events observed for nimesulide-treated patients were similar to
      those of the placebo group. Nimesulide was particularly well tolerated by the
      liver, lungs, kidneys and blood.

PMID- 7506191
TI  - Nimesulide as a downregulator of the activity of the neutrophil myeloperoxidase
      pathway. Focus on the histoprotective potential of the drug during inflammatory
      processes.
AB  - Neutrophils, recruited to tissue sites of inflammation, release a variety of
      oxidants and enzymes, which are responsible for tissue damage. Among the oxidants
      released are potent chlorinated compounds, such as hypochlorous acid and
      chloramines, which induce tissue cell damage and inactivate protease inhibitors,
      particularly alpha 1-antitrypsin, the specific inhibitor of neutrophil elastase.
      In studying a rational approach to the pharmacological control of neutrophil
      mediated tissue injury, we investigated the activity of the anti-inflammatory
      drug nimesulide. This agent reduced the function of the myeloperoxidase pathway
      (which generates hypochlorous acid), by exerting a cell-directed inhibitory
      activity, as shown by measurement of superoxide anion and hydrogen peroxide
      production. Nimesulide also inactivated hypochlorous acid directly and protected
      alpha 1-antitrypsin from the neutrophil-mediated oxidation. Thus, neutrophil
      elastolytic activity may be attenuated by nimesulide-spared alpha 1-antitrypsin.
      The prevention of oxidative inactivation of alpha 1-antitrypsin by nimesulide
      strictly correlates with the drug's ability to suppress the extracellular
      availability of hypochlorous acid. Taken together, these data suggest that
      nimesulide may prevent tissue injury at sites of inflammation by maintaining
      natural host protective systems.

PMID- 7506192
TI  - Effects of nimesulide and naproxen on the degradation and metalloprotease
      synthesis of human osteoarthritic cartilage.
AB  - The aim of this study was to examine the effects of 2 nonsteroidal anti
      inflammatory drugs (NSAIDs), nimesulide and naproxen, on the proteoglycan matrix
      breakdown and metalloprotease synthesis of human osteoarthritic cartilage. The
      results showed that, under in vitro conditions, these 2 NSAIDs could
      significantly reduce both the degradation of proteoglycan and stromelysin
      synthesis. However, only nimesulide had the ability to significantly reduce
      collagenase synthesis. The effectiveness of these drugs on the natural course of
      osteoarthritis remains to be established by clinical studies.

PMID- 7506194
TI  - Antipyretic and platelet antiaggregating effects of nimesulide.
AB  - Nimesulide strongly inhibited ex vivo platelet aggregation in guinea-pigs after
      both single and repeated (once daily for 5 days) oral dosing, irrespective of the
      aggregating agent used (adenosine diphosphate, arachidonic acid or collagen). Its
      potency was consistently greater than that shown by either ticlopidine or
      acetylsalicylic acid. In both oral and rectal administration, nimesulide proved
      to be more active and longer lasting than paracetamol in inhibiting fever induced
      in rats injected subcutaneously with brewer's yeast.

PMID- 7506193
TI  - Recent contributions to knowledge of the mechanism of action of nimesulide.
AB  - Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) of the sulfonanilide
      class. Its anti-inflammatory, analgesic and antipyretic activities have been
      demonstrated in several widely used animal experimental models and in numerous
      clinical trials. Nimesulide only weakly inhibits prostaglandin synthesis and
      appears to exert its effects through various mechanisms. It inhibits the release
      of oxidants from activated neutrophils and has a scavenging effect on
      hypochlorous acid without affecting neutrophil function. Nimesulide also
      decreases histamine release from tissue mast cells and inhibits the production of
      platelet-activating factor by human basophils. Furthermore, when added in vitro
      to cultures of human articular chondrocytes, nimesulide inhibits the release of
      stromelysin and blocks metalloproteinase activity.

PMID- 7506196
TI  - The pharmacokinetic profile of nimesulide in healthy volunteers.
AB  - After oral administration of nimesulide 100mg in tablet, granule or suspension to
      healthy volunteers, the drug was rapidly and extensively absorbed. Mean peak
      plasma concentrations of 2.86 to 4.58 mg/L were achieved within 1.22 to 3.83
      hours of administration. The presence of food did not reduce either the rate or
      the extent of nimesulide absorption. When administered in suppository form,
      nimesulide peak plasma concentrations were lower and occurred later than those
      achieved after oral administration; the bioavailability of nimesulide given by
      suppository ranged from 54 to 96%, relative to that of orally administered
      formulations. Nimesulide is rapidly distributed, principally throughout the
      extracellular fluid compartment; values for volume of distribution ranged from
      0.19 to 0.39 L/kg. Nimesulide is extensively bound to plasma proteins: at
      concentrations ranging from 0.5 to 10 mg/L, the unbound fraction varied between
      0.7 and 4.0%. With oral administration, nimesulide concentrations decline
      monoexponentially following peak levels. The estimated mean terminal half-life
      for nimesulide varied from 1.96 to 4.73 hours. Excretion of unchanged drug in
      urine and faeces is negligible. Nimesulide is mainly eliminated by metabolic
      transformation and the principal metabolite is the 4'-hydroxy derivative. The
      presence of other metabolites is being evaluated. Excretion of nimesulide
      metabolites in the urine and faeces accounts for about 80 and 20% of the
      administered dose, respectively. Total plasma clearance of nimesulide was 39.7 to
      90.9 ml/h/kg, reflecting almost exclusive metabolic clearance. The drug has a low
      extraction ratio, close to 0.1. Differences in gender have only a limited
      influence on the pharmacokinetic profile of nimesulide and its hydroxylated
      metabolite. With twice-daily administration of nimesulide 100 mg (tablets) or
      200mg (suppositories), steady-state is achieved within 24 to 36 hours (2 to 3
      administrations). With oral nimesulide 100mg twice daily, only modest
      accumulation of nimesulide and its 4'-hydroxy derivative occurs (Rmin, 1.59 for
      nimesulide and 1.46 for the hydroxylated metabolite).

PMID- 7506195
TI  - Nimesulide inhibits platelet-activating factor synthesis in activated human
      neutrophils.
AB  - In an inflammatory locus, products of activated neutrophils may be toxic both to
      the micro-organisms to be eliminated and to the surrounding tissue. In several
      models of inflammation, nimesulide possesses marked anti-inflammatory properties.
      The present study was undertaken to further investigate the effects of nimesulide
      on the activation of human neutrophils. Nimesulide caused a concentration
      dependent inhibition of the homotypic aggregation of neutrophils upon activation
      with the receptor agonist formyl-Met-Leu-Phe. Likewise, nimesulide inhibited the
      heterotypic interaction of human neutrophils with endothelial cells in
      suspension. Since both these responses are mediated through activation of the
      integrin CD11b/CD18 on the neutrophil surface, we conclude that nimesulide
      interferes with the signal transduction leading to this activation. We also
      observed a strong inhibition of platelet-activating factor (PAF) synthesis by
      activated neutrophils in the presence of nimesulide. PAF has been implicated as
      an intercellular messenger in the diapedesis of neutrophils across endothelial
      cell monolayers after treatment with cytokines and in the activation of
      eosinophils.

PMID- 7506197
TI  - Effect of age and disease on the pharmacokinetics of nimesulide.
AB  - Nimesulide is a nonsteroidal anti-inflammatory agent with additional antipyretic
      and analgesic activity. The recommended dosage is 100 to 200 mg twice daily
      orally or rectally. The pharmacokinetics profile of nimesulide has been studied
      in patients with a predisposition for altered pharmacokinetics. The
      pharmacokinetic profile of nimesulide and its hydroxy metabolite was not altered
      when the drug was administered in a standard regimen (100mg twice daily) to
      elderly patients aged < 80 years, suggesting that dosage adjustment is not
      necessary for such patients. In children aged 7 to 9 years, nimesulide 50mg
      administered in a granular formulation showed a tendency for greater absorption
      and elimination than that recorded for adults administered nimesulide in tablet
      form. These results suggest that the pharmacokinetic profile of this paediatric
      formulation should be assessed in children aged < 7 years to determine whether
      their dosage should be adjusted. In patients with moderate renal insufficiency,
      the pharmacokinetic profile of nimesulide was not altered even though the
      terminal elimination half-life of its hydroxy metabolite was greater and this
      resulted in slight accumulation with multiple dose administration in a standard
      regimen. This slight effect was not considered to be clinically significant and
      therefore dosage adjustment for patients with moderate renal impairment appears
      unnecessary. Administration of nimesulide to patients with severe renal failure
      should be avoided until the propensity and significance of hydroxy-nimesulide
      accumulation is quantified in this patient group. The pharmacokinetic profile of
      nimesulide has not been determined in patients with hepatic disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7506198
TI  - Drug interactions with nimesulide.
AB  - Nimesulide is a recently developed analgesic, antipyretic and anti-inflammatory
      agent that differs from conventional nonsteroidal anti-inflammatory drugs both in
      structure and pharmacological profile. Since nimesulide may be prescribed for
      patients receiving concomitant medication, the propensity for drug interactions
      exists. Investigations have been conducted to assess the potential for
      pharmacokinetic and pharmacodynamic interaction. With regard to absorption, there
      is some evidence that nimesulide may decrease the oral bioavailability of
      furosemide (frusemide). Nimesulide is extensively bound to plasma proteins and
      may be displaced from binding sites by concurrently administered drugs such as
      fenofibrate, salicylic acid and tolbutamide. In addition, nimesulide may displace
      salicylic acid and furosemide (but not warfarin) from plasma proteins. Major
      interactions involving interference with drug metabolism have not been described
      with nimesulide. A marginal decrease in plasma theophylline levels (without
      changes in respiratory function tests) has been described after addition of
      nimesulide to chronic theophylline therapy. Despite earlier suggestions that
      nimesulide may increase the hypoglycaemic effect of glibenclamide, a formal study
      excluded any influence of the drug on fasting blood sugar and glucose tolerance
      in diabetic patients treated with various sulfonylureas. Although nimesulide does
      not usually affect the response to warfarin, a few patients may show some
      increase in anticoagulant effect; therefore, it would seem prudent to monitor
      coagulation status when the 2 drugs are administered together. Finally,
      nimesulide may reduce the natriuretic response to furosemide and potentiate the
      furosemide-induced reduction in glomerular filtration rate and renal blood flow,
      through a pharmacodynamic interaction which is likely to involve inhibition of
      renal cyclo-oxygenase. These results suggest that caution should be exercised
      when nimesulide is used in combination with drugs that are known to adversely
      affect renal haemodynamics.

PMID- 7506199
TI  - Nimesulide binding to components within blood.
AB  - The binding of nimesulide within human serum to isolated proteins and to
      erythrocytes was studied by equilibrium dialysis. Within the range of therapeutic
      concentrations, nimesulide was 99% bound to serum involving a nonsaturated
      process (NKA = 91). This binding was almost identical to binding of nimesulide to
      serum albumin (NKA = 95). Physiological concentrations of free fatty acids did
      not affect binding of nimesulide to serum albumin. The retention of nimesulide by
      erythrocytes suspended in buffer was moderate (67%), although in whole blood no
      erythrocyte binding was observed because of the greater affinity of this drug for
      serum. Over the range of therapeutic concentrations (2.5 to 63 mumol/L), the free
      fraction of nimesulide in serum remains constant. Serum binding was decreased in
      samples obtained from patients with renal failure or hepatic cirrhosis associated
      with hypoalbuminaemia and hyperbilirubinaemia, respectively. At therapeutic
      concentrations, the binding of nimesulide was unaffected by warfarin,
      cefoperazone, furosemide (frusemide), glibenclamide, tamoxifen or digitoxin.
      However, valproic acid and fenofibrate (80 mumol/L) may displace nimesulide. 4
      Hydroxy-nimesulide, the principal metabolite, significantly increased the free
      fraction of nimesulide. Although methotrexate had no effect on the free fraction
      of nimesulide, the free fraction of methotrexate was significantly increased in
      the presence of nimesulide. The present study also demonstrated 2 distinct
      nimesulide binding sites (site I and site II) on serum albumin (10 mumol/L) with
      different affinities: site II KA = 3.57 x 10(5) L/mol and site I KA = 1.24 x
      10(5) L/mol. Interaction studies using markers that bind specifically to site I
      (warfarin and azapropazone) and site II (diazepam and ibuprofen) indicated that
      nimesulide binds to site II with higher affinity and to a lesser extent to site
      I.

PMID- 7506200
TI  - A clinical assessment of the potential for pharmacological interaction between
      nimesulide and digoxin in patients with heart failure.
AB  - The potential interaction between nimesulide, a nonsteroidal anti-inflammatory
      drug, and digoxin was studied in 9 patients [6 males, 3 females; mean age 67
      (range 57 to 70) years] with mild heart failure. All patients were receiving
      maintenance therapy with digoxin (0.25 mg/day, orally) and were treated with oral
      nimesulide 100mg twice daily for 7 days. Blood samples were collected at 8am and
      6pm for 4 days before and throughout the nimesulide treatment period for
      determination of serum digoxin concentrations. Physical health,
      electrocardiographic recordings and blood and urine samples were also monitored.
      Mean serum digoxin concentrations remained within the normal therapeutic range
      throughout the study despite large interindividual variation. Furthermore, there
      were no significant differences between the morning and afternoon serum digoxin
      concentrations and there was no major change in the clinical condition of any
      patient. These results indicate that short term administration (7 days) of
      conventional therapeutic doses of nimesulide (100mg twice daily) does not modify
      the serum digoxin profile in patients with low class heart failure treated with a
      maintenance dose (0.25 mg/day) of this cardiac glycoside.

PMID- 7506201
TI  - A multicentre clinical study of nimesulide in inflammatory diseases of the ear,
      nose and throat.
AB  - 940 male and female patients aged 15 to 77 years were enrolled in a multicentre
      noncomparative study in order to assess the efficacy and tolerability of
      nimesulide in otorhinolaryngological inflammatory diseases. 309 patients were
      affected by otitis media and 631 by upper respiratory tract inflammation. All the
      patients were treated with orally administered granular nimesulide 100mg twice
      daily for a mean period of 10 days. Nimesulide significantly reduced the
      intensity of signs and symptoms, thus allowing functional recovery. The drug was
      well tolerated, and of the 75 patients who reported adverse effects, only 26 had
      to be withdrawn from treatment.

PMID- 7506202
TI  - Calbindin-D9k gene expression in the uterus: study of the two messenger
      ribonucleic acid species and analysis of an imperfect estrogen-responsive
      element.
AB  - The calbindin D9k (CaBP9k) gene is under strict estrogen control in the rat
      uterus. This tissue contains two CaBP9k messenger RNA (mRNA) species. We have
      used primer extension analysis, reverse transcriptase associated with polymerase
      chain reaction, and RNase H digestion to show that these two mRNA species have
      the same structural features, including 5'- and 3'-ends, and poly(A) tail length.
      Our results suggest that the difference in electrophoretic mobilities of the two
      mRNA species might be due to interaction with another factor. We also analyzed
      the imperfect estrogen-responsive element (ERE) present on the first 5'-splice
      site of the rat CaBP9k gene. The oligonucleotide corresponding to the CaBP9k ERE
      was cloned in the plasmid pBLCAT2 (where the thymidine kinase promoter governs
      the expression of the chloramphenicol acetyl transferase gene) and transfected
      into MCF7 cells. This CaBP9k ERE was found to be a hormone-inducible enhancer
      that worked in an orientation-independent manner on a heterologous promoter and
      was functional at physiological hormone concentrations. One CaBP9k ERE conferred
      only weak (about 2-fold) estrogen induction, but two EREs cloned in tandem were
      strongly synergistic (14- to 16-fold). The CaBP9k ERE also bound to the partially
      purified estrogen receptor (ER) and to ER expressed in COS cells by gel shift
      assay. Methylation interference showed that all the guanine residues in both half
      sites of the CaBP9k ERE were protected by ER binding. Thus, ER binds to the
      CaBP9k ERE in a way similar to other EREs. The gel shift assay results indicate
      that the strong synergistic effect of two EREs cloned in tandem is not due to
      cooperative binding between the two elements. As the CaBP9k gene is under strong
      estrogenic control in the uterus in vivo, the imperfect CaBP9k ERE may cooperate
      with another trans-acting factor to become fully efficient.

PMID- 7506203
TI  - Glucocorticoid regulation of insulin-like growth factor-binding protein
      expression in normal human osteoblast-like cells.
AB  - Glucocorticoid (GC) modulates insulin-like growth factor (IGF) action in bone
      through mechanisms that are complex and not well understood. Because the family
      of IGF-binding proteins (IGFBP-1 through -6) is important in the regulation of
      IGF availability and bioactivity, we examined the effect of GC on IGFBP
      expression in normal human osteoblast-like (hOB) cells. As assessed by Western
      ligand blot, hOB cells release IGFBP-3, IGFBP-4, and a 31-kilodalton IGFBP, which
      appeared to be IGFBP-5. Northern analysis revealed that hOB cells express
      abundant IGFBP-3, IGFBP-4, IGFBP-5, and IGFBP-6 mRNA, with barely detectable
      IGFBP-1 mRNA. GC treatment resulted in time- and dose-dependent decreases in
      IGFBP-3, IGFBP-4, and 31-kilodalton IGFBP levels in culture medium, with
      corresponding decreases in IGFBP-3, IGFBP-4, and IGFBP-5 mRNA levels. In
      addition, GC treatment increased steady state levels of IGFBP-1 mRNA and did not
      alter IGFBP-6 mRNA levels. Although hOB cells secrete an acid-activated IGFBP-3
      protease and an IGF-dependent IGFBP-4 protease, GC had little effect on these
      protease activities and did not alter degradation of the secreted IGFBPs. Our
      results indicate that GC has dramatic effects on IGFBP gene expression and
      suggest that differential regulation of IGFBPs by GC may modulate hOB cell
      responsiveness to IGFs.

PMID- 7506204
TI  - Stimulation of lactotrope differentiation in vitro by fibroblast growth factor.
AB  - We have reported previously that differentiation of PRL-secreting cells in rats
      is regulated by a maternal peptide transferred to the neonatal circulation after
      ingestion of mothers' milk. Inasmuch as milk contains numerous hormones and
      biologically active peptides, the present study was designed to test the capacity
      of various growth factors and hypothalamic peptides at inducing the
      differentiation of PRL cells in vitro. Anterior pituitary cells from 1-day-old
      rat pups were cultured in a serum-free system for 6 days with a wide
      concentration range of each test peptide. After this culture period, lactotrope
      differentiation was assessed by subjecting the anterior pituitary cells to
      reverse hemolytic plaque assays for PRL. Our efforts were focused on those growth
      factors and hypophysiotropic peptides found in milk and/or known to regulate
      pituitary function. Included among these were TRH, GH-releasing factor,
      somatostatin, vasoactive intestinal peptide, angiotensin-II, insulin-like growth
      factor-I and -II, LH-releasing hormone, arginine vasopressin, and acidic and
      basic fibroblast growth factors (aFGF and bFGF, respectively). Of these peptides,
      only aFGF and bFGF were capable of stimulating lactotrope differentiation.
      Specifically, we found that maximally effective concentrations of aFGF and bFGF
      increased the percentage of PRL-releasing cells by almost 8-fold, from about 0.5%
      to over 4% of all pituitary cells. In addition, bFGF was found to be about 10
      fold more potent than aFGF at inducing the differentiation of PRL secretors, with
      minimum effective doses approaching 10(-11) and 10(-10) M for bFGF and aFGF,
      respectively. These results suggest that bFGF is a strong candidate to subserve a
      role in regulating the differentiation of lactotropes in vivo.

PMID- 7506205
TI  - Prostaglandin E2 enhances human endometrial stromal cell differentiation.
AB  - Endometrial stromal differentiation (decidualization) is essential for
      implantation of the developing blastocyst. Because prostaglandins (PGs) are
      synthesized in the endometrium, and PG-binding sites have been demonstrated in
      the proliferative endometrial stromal cell (the precursor of the decidual cell),
      experiments were performed to determine whether PGs are involved in the process
      of decidualization. Human endometrial stromal cells were cultured for 18 days in
      Dulbeco's Modified Eagle's Medium-2% fetal bovine serum with 1 microM
      medroxyprogesterone acetate (MPA) and 10 nM estradiol, with and without PGE2 or
      PGF2 alpha. Expression of PRL was used as a marker of decidualization. In the
      presence of estradiol and MPA alone (control), PRL was detected beginning on day
      9 and gradually increased through day 18. In contrast, PRL was detected on day 3
      in the PGE2-treated cells, and the magnitude of stimulation in these cells on
      days 9-12 was 1300-1400% of that in control cells. Furthermore, the PRL mRNA
      content of the PGE2-treated cells on day 12 was 4.6-fold greater than that in the
      control cells. The effect of PGE2 on PRL production was dose dependent, with a
      minimal effective dose of 10(-10) M. PGE2 in the absence of steroids had a
      minimal effect on PRL production. In contrast to PGE2, PGF2 alpha treatment had
      no effect on PRL expression in steroid-treated cells. These results indicate that
      there are synergistic effects among PGE2, estradiol, and MPA, resulting in
      acceleration of endometrial stromal cell differentiation and enhanced PRL
      expression.

PMID- 7506206
TI  - Progestin-induced growth hormone excess in the dog originates in the mammary
      gland.
AB  - In the dog endogenous progesterone and synthetic progestins may incite
      overproduction of GH, resulting in acromegaly and insulin resistance. This
      progrestin-induced excessive GH secretion is characterized by disappearance of
      the pulsatile secretion pattern and insensitivity to both stimulation with GHRH
      and inhibition with a somatostatin analog. This progestin-induced GH
      hypersecretion is not associated with neoplastic transformation at the pituitary
      level. These observations were the impetus for a search of a possible
      extrapituitary site of GH production. In four ovariohysterectomized dogs elevated
      plasma GH levels (46.5 +/- 7.7 micrograms/liter; mean +/- SEM) were induced by
      administration of synthetic progestins. In these dogs hypophysectomy did not led
      to a significant decrease in plasma GH levels. Analysis of the GH content of
      various tissue homogenates revealed that the highest GH immunoreactivity was
      found in extracts of the mammary gland. Ectopic production of GH in the mammary
      gland was confirmed by lowering of plasma GH concentration to values within the
      reference range within 2 h after complete mammectomy in two dogs with progestin
      induced elevations of plasma GH levels. In one of these dogs the arterial and
      elevations of plasma GH levels. In one of these dogs the arterial and venous GH
      concentrations across the mammary gland were measured and an arterio-venous GH
      gradient was demonstrated. Displacement studies in the RIA and analysis by
      reversed-phase HPLC revealed that mammary-derived GH is highly similar to
      pituitary-derived GH. Immuno-histochemical staining revealed that GH
      immunoreactivity was localized in focal areas of hyperplastic ductular
      epithelium. In mammary tissue of healthy untreated female dogs no GH
      immunoreactivity was found. It is concluded that treatment of dogs with synthetic
      progestins can induce the overproduction of GH in the mammary gland. This GH is
      biologically active, highly similar to pituitary derived GH, and originates from
      foci of hyperplastic ductular epithelium of the mammary gland.

PMID- 7506207
TI  - Aging impairs galanin expression in luteinizing hormone-releasing hormone
      neurons: effect of ovariectomy and/or estradiol treatment.
AB  - In the medial preoptic area and the diagonal band of Broca, a subset of LHRH
      neurons coexpresses galanin at a 4- to 5-fold higher rate in female than male
      rats, suggesting that estradiol (E2) plays a key role in galanin gene expression
      within LHRH neurons. In the present studies we investigated the incidence of
      colocalization of these peptides in different age groups, i.e. 2-, 10-, 18-, and
      24-month-old intact female Fisher rats; 24-month-old E2-treated rats; 24-month
      old ovariectomized (OVX) rats; and 24-month-old OVX E2-treated rats with single
      or double labeling immunocytochemistry. For cell counting, we took advantage of
      the typical fusiform morphology of galanin-immunoreactive neurons that colocalize
      LHRH. The presence of both peptides in the same perikaryon was substantiated by
      double staining representative sections from each brain. Our observations
      indicate that the number of galanin/LHRH-coexpressing perikarya dramatically
      decreased with age. Although in 18-month-old rats a moderate decline was
      observed, in 24-month-old female rats no, or only a few, faintly stained,
      fusiform galanin-immunopositive perikarya were present. Although galanin was
      absent from LHRH neurons of aged rats, their LHRH content was not altered. E2
      treatment of intact 24-month-old rats had no effect on the low incidence of
      colocalization. However, when OVX 24-month-old rats were E2 treated, the
      incidence of colocalization increased to the level seen in 2- or 10-month-old
      estrous animals. Our observations on the presence of colocalizing perikarya in
      intact and E2-treated aged animals provide further evidence for the key role of
      E2 in galanin gene expression within LHRH neurons and emphasize that some ovarian
      factor(s) may blunt this effect.

PMID- 7506208
TI  - Effect of triamcinolone on parathyroid hormone-stimulated second messenger
      systems and phosphate transport in opossum kidney cells.
AB  - Although PTH is known to stimulate both the adenylate cyclase/protein kinase-A
      system and the phospholipase-C/protein kinase-C second messenger systems, the
      relative roles of these second messenger pathways remain unclear. The present
      studies were designed to examine the effect of triamcinolone on PTH-stimulated
      second messenger systems and phosphate transport in confluent cultures of opossum
      kidney cells. Triamcinolone was added to these cultures at a concentration of 10
      nM for 24-48 h. Neither cell number nor protein content was changed by this
      treatment. The addition of triamcinolone did not alter PTH receptor binding or
      competitive displacement radioligand binding assay curves. PTH-stimulated cAMP
      generation and activation of protein kinase-A were not altered by triamcinolone.
      The glucocorticoid, however, increased basal phosphate uptake from 1.0 +/- 0.1 to
      1.28 +/- 0.1 pmol/5 min.culture (P < 0.01). Phosphate transport was significantly
      decreased by PTH (0.01 nM) in the triamcinolone-treated cultures, but not in
      control cultures. Phosphate uptake in the presence of maximal doses of PTH was
      similar in both control and triamcinolone-treated cultures. Thus, the PTH
      responsive component of phosphate transport was preserved, and the threshold dose
      for the effect of PTH was reduced after treatment with triamcinolone. Studies
      were then performed to evaluate the alternate second messenger pathway. In
      control cultures, PTH rapidly increased the level of diglyceride mass, as
      measured by diglyceride kinase assay, from 0.18 +/- 0.01 to a peak of 0.26 +/-
      0.02 mol/100 mol total phospholipid (P < 0.002), 1 min after addition of the
      hormone. Triamcinolone pretreatment for 48 h, however, elevated the basal
      diglyceride levels, but the increase after the addition of PTH was totally
      abolished. The absence of an increase in diglyceride upon stimulation with PTH
      correlated with elimination of the PTH-stimulated increase in the activity of
      particulate protein kinase-C. Thus, in triamcinolone-treated cells, the effect of
      PTH on phosphate transport was preserved, and the threshold dose of PTH-induced
      alteration in phosphate transport was reduced in the absence of stimulation of
      this alternate second messenger pathway. These data show that triamcinolone in
      opossum kidney cells does not alter PTH activation of the cAMP/protein kinase-A
      system, but eliminates the increase in diglyceride and the activation of protein
      kinase-C in response to PTH. These studies emphasize the major role of the
      protein kinase-A system in the regulation of phosphate transport by PTH.

PMID- 7506209
TI  - Proteolytic degradation of insulin-like growth factor (IGF)-binding protein-3 by
      porcine ovarian granulosa cells in culture: regulation by IGF-I.
AB  - Porcine ovarian granulosa cells in culture secrete glycosylated insulin-like
      growth factor (IGF)-binding protein-3 (IGFBP-3), which inhibits gonadotropin and
      IGF action in the ovary. Synthesis of IGFBP-3 is stimulated by IGF-I and
      attenuated by gonadotropin. The purpose of the present study was to determine
      whether IGFBP-3 levels were also regulated via proteolysis. Exogenously added
      nonglycosylated recombinant human IGFBP-3 (rhIGFBP-3) was significantly degraded
      over time by a soluble serine-specific protease, similar to plasmin, in control
      cultures and those treated with FSH, insulin, or several other classes of
      hormones. In contrast, degradation was greatly attenuated by the IGFs. Degraded
      rhIGFBP-3 exhibited much reduced affinity for [125I]IGF-II, suggesting that
      degradation could make available IGFs for cellular interaction. The mechanism of
      IGFBP-3 protease inhibition by IGFs is unclear. Mediation by IGF receptors is
      unlikely, as insulin at a dose that activated both insulin and type I IGF
      receptors did not alter intrinsic degradation of IGFBP-3 (as does IGF).
      Additionally, IGF-I attenuation of IGFBP-3 degradation was not inhibited by
      antagonism of receptor action with a tyrosine kinase inhibitor. Further, IGF-I
      inhibited degradation in cell-free conditioned medium. Direct stabilization of
      IGFBP-3 via binding of IGFs was suggested from these results. However, long R3
      IGF-I attenuated IGFBP-3 degradation even though it has low affinity for IGFBPs.
      Inhibition of the protease by IGFs is also possible. We conclude that IGFs
      inhibit the degradation of exogenous nonglycosylated rhIGFBP-3. If active in
      vivo, this may serve to increase endogenous IGFBP-3 levels in follicular fluid.

PMID- 7506210
TI  - Parathyroid hormone and hydrochlorothiazide increase calcium transport by the
      luminal membrane of rabbit distal nephron segments through different pathways.
AB  - The present study was designed to investigate the effect of PTH on calcium (Ca2+)
      transport through the luminal membrane of proximal and distal rabbit tubule
      segments. Proximal tubule and distal tubule segment suspensions were incubated
      with the hormone, and the luminal membranes were subsequently purified.
      Incubation with 10(-8) M human PTH(1-34) strongly increased initial Ca2+ uptake
      by the distal membranes. The effect of PTH was dose dependent, with an apparent
      ED50 of 8.2 +/- 1.0 nM. We recently reported the presence of two kinetics of Ca2+
      uptake by the distal luminal membranes. PTH affected exclusively the high
      affinity component, increasing the maximum velocity from 0.31 +/- 0.02 to 0.76 +/
      0.07 pmol/micrograms.10 sec (P < 0.001), and leaving the Michaelis-Menten
      constant Ca2+ unchanged. The addition of 500 microM hydrochlorothiazide (HCTZ) to
      the luminal membranes of distal tubules incubated with PTH further enhanced Ca2+
      uptake. The effect of HCTZ was on the low affinity system. HCTZ (100 microM)
      enhanced the maximum velocity from 2.5 +/- 0.3 to 3.7 +/- 0.6 pmol/micrograms
      protein.10 sec (P < 0.01) without affecting the Michaelis-Menten constant.
      Whereas 1 microM nitrendipine alone did not affect Ca2+ transport by the distal
      tubule luminal membranes, the Ca2+ channel inhibitor completely abolished the
      effect of PTH. Conversely, 1 microM Bay K 8644 increased Ca2+ uptake by membranes
      from PTH-treated distal tubules but was ineffective in membranes from control
      tubules. Neither PTH nor nitrendipine nor Bay K 8644 had any effect on the
      luminal membranes from proximal tubules. These results suggest that: 1) the high
      affinity, low velocity Ca2+ transport system in the luminal membrane from distal
      cortical segments is sensitive to PTH; 2) the effects of nitrendipine and Bay K
      8644 on Ca2+ uptake were observed only in membranes from tubules incubated with
      PTH; 3) this uptake is distinct from the thiazide-sensitive Ca2+ transport
      system; and 4) PTH does not influence Ca2+ transport by the luminal membrane of
      proximal tubules.

PMID- 7506211
TI  - Evidence that human bone cells in culture produce insulin-like growth factor
      binding protein-4 and -5 proteases.
AB  - Previous studies have shown that the actions of insulin-like growth factor-II
      (IGF-II) in bone are determined by both its concentration and the concentrations
      of the IGF-binding proteins (IGFBPs). As IGFBP concentrations may be regulated
      not only at the level of production, but also at the level of degradation, IGFBP
      proteases may be an important component of the IGF-II regulatory system. In this
      study, we have identified IGFBP-4 and IGFBP-5 protease activity in the
      conditioned medium (CM) of the human osteosarcoma U2 cell line (U2OS) and
      untransformed normal human bone cell (HBC) derived from skull. Proteolysis of the
      29-kilodalton (kDa) [125I]IGFBP-5 produced an 18- to 20-kDa fragment of IGFBP-5,
      and 25 kDa [125I]IGFBP-4 yielded two lower mol wt fragments in the presence of
      IGF-II. CM from IGF-II-treated U2OS and normal HBC cultures exhibited decreased
      IGFBP-5 proteolytic activity compared to control cultures. In contrast, CM from
      IGF-II-treated HBC cultures had increased proteolytic activity against IGFBP-4.
      To determine the mechanisms by which IGF-II modulates IGFBP-4 and -5 proteolytic
      activity, CM from control U2OS cell culture was incubated with [125I]IGFBP-4 or 
      5 in the presence of various concentrations of IGF-II and IGF analogs under cell
      free conditions. It was found that exogenous IGF-II stimulated IGFBP-4
      proteolysis, but IGF analogs that had no or extremely low affinity to IGFBP-4
      failed to induce IGFBP-4 proteolysis. On the contrary, exogenous IGF-II had no
      effect on IGFBP-5 proteolysis in cell-free U2OS CM. Both IGFBP-4 and IGFBP-5
      proteolytic activities were inhibited by aprotinin, zinc chloride, and EDTA and
      eluted as a single major peak between mol wt markers of 160 and 67 kDa upon gel
      filtration. Based on the findings that HBCs in culture produce a protease(s)
      capable of cleaving both IGFBP-4 and IGFBP-5 and that IGF-II can promote or
      inhibit proteolytic degradation of IGFBP-4 and IGFBP-5, respectively, it is
      proposed that IGFBP protease(s) may be an important modulator of IGF activity in
      bone.

PMID- 7506212
TI  - Constitutively active stimulatory G-protein alpha s in beta-cells of transgenic
      mice causes counterregulation of the increased adenosine 3',5'-monophosphate and
      insulin secretion.
AB  - To evaluate the effect of chronically elevated adenylyl cyclase, we targeted the
      expression of a constitutively active mutant alpha-subunit (alpha s+) of Gs to
      the insulin-producing pancreatic beta-cells of transgenic mice. As assessed by
      the polymerase chain reaction, expression of alpha s+ mRNA was restricted to the
      transgenic pancreas. Histological analysis by light microscopy and
      immunohistochemistry for insulin, glucagon, and somatostatin appeared normal in
      transgenic islets. Pancreatic insulin content was quantitatively the same for
      alpha s+ transgenic and control mice. Comparisons of glucose homeostasis, insulin
      secretion, and islet cAMP revealed the expected differences between alpha s+
      transgenic and control mice; in every case, however, responses to glucose alone
      were normal, and the differences were observed only when measurements were
      performed in the presence of isobutylmethylxanthine (IBMX), an inhibitor of cAMP
      phosphodiesterase. 1) In vivo, ip glucose tolerance was normal in alpha s+
      transgenics; when ip glucose was preceded by administration of IBMX, the rise in
      blood glucose was approximately 33% less in the transgenic than in the control
      mice. 2) Insulin secretion from the perfused pancreas stimulated sequentially
      with 11 and 22 mM glucose caused characteristic first and second phase insulin
      release that did not differ between transgenic and control pancreases. IBMX
      increased biphasic insulin release from all pancreases, but caused a 2-fold
      greater than normal release from the transgenics. 3) Similarly, batch-incubated
      alpha s+ and control islets secreted equivalent amounts of insulin in the
      presence of glucose (22 mM) alone, whereas the combination of glucose plus IBMX
      was twice as effective on alpha s+ islets. 4) Islet cAMP levels paralleled
      insulin secretion; in the presence of IBMX, but not glucose alone, cAMP was
      increased 2-fold more in alpha s+ vs. control islets. We conclude that expression
      of constitutively active alpha s mutant in pancreatic beta-cells of transgenic
      mice is functionally effective, causing the physiological phenotype of increased
      islet cAMP and insulin secretion. However, these changes are uncovered only in
      the presence of IBMX; without IBMX, glucose homeostasis and islet function appear
      normal. This normalization, or counterregulation, of cAMP synthesis presumably is
      accomplished by a compensatory increase in cAMP degradation, possibly via
      increased activity of cAMP phosphodiesterase.

PMID- 7506213
TI  - Reduced chondroclast differentiation results in increased cancellous bone volume
      in estrogen-treated growing rats.
AB  - These studies were designed to investigate the role of altered growth processes
      in mediating estrogen-induced changes in cancellous bone volume in growing female
      rats. Ovariectomy resulted in an increase in the longitudinal growth rate of the
      tibia throughout the growth period and estrogen treatment of ovariectomized (OVX)
      rats resulted in a dose-dependent decrease in longitudinal growth. Estrogen
      treatment also resulted in decreases in growth plate thickness, chondroclast
      number in the zone of vascular invasion, and osteoclast number in the secondary
      spongiosa. There were simultaneous increases in mineralized cartilage in the zone
      of vascular invasion; total mineralized tissue, mineralized cartilage, and bone
      in the primary spongiosa; and bone in the secondary spongiosa. Ovariectomy
      increased and estrogen treatment of OVX rats decreased [3H]thymidine-labeled
      nuclei in chondroclasts after 24 h, but after 7 days, the labeling indices were
      similar in the OVX and intact groups and only slightly decreased in the estrogen
      treated rats. We interpret these results as evidence that estrogen impairs
      chondroclast differentiation. We propose that this impairment leads to decreased
      chondroclast number and reduced resorption of mineralized cartilage in the zone
      of vascular invasion, which, in turn, results in an increased cancellous bone
      volume.

PMID- 7506214
TI  - Cloricromene inhibits the induction of nitric oxide synthase.
AB  - The effect of cloricromene, a coumarin derivative, was investigated on the
      lipopolysaccharide-stimulated nitric oxide (NO) synthase induction in intact
      aortas from endotoxin shocked rats and in the murine macrophage cell line J774.
      Rings of thoracic aortas from lipopolysaccharide (4 mg/kg, i.v.)-shocked rats,
      contracted with phenylephrine, showed a progressive decrease in tone, that was of
      a greater magnitude than that of aortas from naive rats. Moreover, a decreased
      response to the constrictor effect of phenylephrine was observed in aortas from
      shocked rats. In vivo treatment with cloricromene (2 mg/kg, i.v.) 30 min before
      lipopolysaccharide administration partially prevented the loss in tone of aortic
      rings and improved their reactivity to phenylephrine. Murine J774 macrophages
      activated with lipopolysaccharide (100 ng/ml) produced significant amounts of
      nitrites (NO2-; 28.2 +/- 3.5 nmol/10(6) cells per 24 h). Cloricromene (2, 20 or
      200 microM) added to the cells concomitantly with lipopolysaccharide inhibited
      NO2- production in a concentration-dependent manner. Maximum inhibition (84.0 +/-
      8.0%) was observed when cloricromene (200 microM) was added to the cells 6 h
      before lipopolysaccharide, whereas it was ineffective when given 6 h after
      endotoxin. These results demonstrate that cloricromene inhibits the expression
      but not the activity of the inducible NO synthase.

PMID- 7506215
TI  - Characterization of vasocortin-like proteins induced by dexamethasone in
      endothelial cells.
AB  - In this study we have shown that dexamethasone induces vasocortin-like proteins
      in bovine endothelial cells as well as in the bovine aortic endothelial cell
      line, GM 7373. Vasocortin-like proteins have been characterized by their ability
      to mimic the glucocorticoid inhibition of rat dextran oedema and histamine
      release induced by concanavalin-A in rat mast cells. Following partial
      purification of these proteins by gel filtration, vasocortin activity was found
      to be associated to proteins with molecular weight between 20-35 kD. This study
      showed that dexamethasone induces vasocortin-like proteins in endothelial cells
      and suggests that endothelial cells are target cells of glucocorticoid activity
      in vascular tissue.

PMID- 7506216
TI  - Ionic channel activity induced by fusion of Rhodospirillum rubrum chromatophores
      with a planar bilayer lipid membrane.
AB  - The present work concerns mechanisms of ionic conductivity of photosynthetic
      membranes. It is shown that reconstitution of vesicles of photosynthetic
      membranes (chromatophores) of purple bacteria Rhodospirillum rubrum into a planar
      bilayer lipid membrane leads to fluctuations of current showing the existence of
      a channel with a predominant conductance of approximately 230 pS in the presence
      of 100 mM KCl. Measurements under the conditions of KCl gradient prove that this
      channel is cation selective (PK/PCl = 7.2). Voltage inactivation of the channel
      is demonstrated which is prevented by treatment with trypsin.

PMID- 7506218
TI  - Potentiating effect of insulin on exocrine secretory function in isolated rat
      pancreatic acini.
AB  - BACKGROUND/AIMS: Insulin is shown to exert various regulatory effects on the
      exocrine pancreatic function. We investigated the direct effect of insulin on
      exocrine pancreatic secretion. METHODS: The effects of insulin on amylase
      release, 125I-secretin binding and Na(+)- and K(+)-activated adenosine
      triphosphate phosphohydrolase (Na+,K(+)-ATPase) activity were measured using the
      isolated rat pancreatic acini. RESULTS: Insulin potentiated the amylase release
      elicited by secretin plus cholecystokinin (CCK), but not by either secretin or
      CCK alone. The potentiating effect of insulin was dependent on the concentration
      and preincubation time. Insulin had no effect on 125I-secretin binding. Ouabain,
      a specific Na+,K(+)-ATPase inhibitor, caused a concentration-dependent inhibition
      of the potentiated secretion by insulin without affecting the secretory response
      to secretin plus CCK. In membranes prepared from acini treated with insulin,
      Na+,K(+)-ATPase activity was significantly increased. Similar results were
      obtained when acini were treated with insulin in combination with secretin plus
      CCK. CONCLUSIONS: Insulin exerts a direct effect on pancreatic acinar cells and
      potentiates exocrine secretion elicited by secretin in combination with CCK, in
      part, by increasing Na+,K(+)-ATPase activity.

PMID- 7506217
TI  - Autoantibodies in sclerosing cholangitis against a shared peptide in biliary and
      colon epithelium.
AB  - BACKGROUND/AIMS: A strong association exists between ulcerative colitis and
      primary sclerosing cholangitis (PSC). Previously, the presence of a unique
      epitope shared by colon and biliary epithelial cells was shown by using the novel
      monoclonal antibody (MAb) 7E12H12 developed against a colonic epithelial protein.
      In the present study, the presence of circulating autoantibody in PSC against
      this peptide was examined. METHODS: Sera from 16 patients with PSC, 13 with
      primary biliary cirrhosis, 6 with secondary biliary stricture, and 6 with chronic
      liver diseases and 10 normal subjects were used. An inhibition immunoperoxidase
      assay using the 7E12H12 MAb was developed against sections of bile duct and
      gallbladder. Sera were also examined in an enzyme-linked immunosorbent assay
      (ELISA) against the gallbladder extract enriched in 7E12H12-reactive protein.
      RESULTS: About two thirds of the sera from patients with PSC blocked the binding
      of 7E12H12 MAb on the bile duct and gallbladder, whereas non-PSC sera did not. In
      the ELISA, 93% of PSC sera had circulating immunoglobulin G antibodies against
      the enriched gallbladder extract. The reactivity of sera from the PSC group was
      significantly (P < 0.01 to P < 0.0001) higher than in each of the non-PSC groups.
      CONCLUSIONS: Sera from patients with PSC contains autoantibodies against a cross
      reactive peptide shared by colon and biliary epithelial cells.

PMID- 7506219
TI  - Co-chairman's remarks: reflections on RNA.

PMID- 7506221
TI  - Co-chairman's remarks: the RNA world: before and after.

PMID- 7506220
TI  - Co-chairman's remarks: genome organization and evolution.
AB  - A full understanding of the evolution of life on earth must include an account of
      the RNA world and of any other informational systems that preceded it.

PMID- 7506222
TI  - Immunohistochemical study of cytokeratin 7 for the differential diagnosis of
      adenocarcinomas in the ovary.
AB  - Mucinous adenocarcinomas of the ovary were studied immunohistochemically for
      cytokeratins 7 and 18, either to determine whether the ovarian tumor was primary
      or a metastasis or to establish the histogenetic origin of the tumor. Primary
      ovarian tumors were strongly positive for both cytokeratins, while ovarian
      metastases from colonic cancers were negative for cytokeratin 7, as were the
      colonic cancers. Three of four ovarian tumors complicated by pseudomyxoma
      peritonei were negative for cytokeratin 7, indicating appendiceal origin. Two of
      seven mucinous tumors associated with dermoid cysts were negative for cytokeratin
      7, suggesting gastrointestinal origin.

PMID- 7506223
TI  - Treatment of chronic hepatitis C with recombinant human interferon-alpha 2a:
      results of a randomized controlled clinical trial.
AB  - Sixty consecutive patients with chronic hepatitis C were included in a randomized
      controlled trial of recombinant human interferon-alpha 2a vs. no treatment.
      Treated patients received tapering doses of interferon thrice weekly for 1 yr.
      Twenty treated cases (66.7%) normalized serum aminotransferase levels within the
      first 4 mo of treatment, but reactivation or breakthrough frequently occurred
      afterward (20% in both cases). Only one of the untreated patients showed
      spontaneous normalization of serum aminotransferase levels. Liver histology did
      not improve in patients without a biochemical response or with breakthrough
      during therapy, whereas it did not worsen in long-term responders and
      reactivating patients. Lack of response does not appear to be related to serum
      interferon antibodies, although their early appearance is more frequent in
      patients who showed reactivation later on. No biochemical parameter was found to
      be predictive for positive response to treatment. Antibody to c100 became
      negative in 62.5% of long-term responders, whereas no change was recorded in
      other treated patients or controls. Reactivation and breakthrough often occur
      during treatment, and further studies are needed to determine the most effective
      schedule (dose and time) of interferon treatment. Loss of c100 antibody during
      therapy may be a marker of long-term maintenance of response to interferon
      therapy.

PMID- 7506224
TI  - Comitogenic effects of estrogens on DNA synthesis induced by various growth
      factors in cultured female rat hepatocytes.
AB  - Ethinyl estradiol is a weak complete carcinogen and potent tumor promoter. In
      vivo, ethinyl estradiol causes a rapid but transient increase in liver growth,
      whereas in cultured female hepatocytes it enhances DNA synthesis induced by
      epidermal growth factor and is thus classified as a comitogen. The objectives of
      this study were to determine: (a) whether estradiol also has comitogenic
      activity; (b) whether the comitogenic effects of estrogen extend to complete
      hepatic mitogens other than epidermal growth factor and (c) whether inhibition of
      hepatocyte DNA synthesis by transforming growth factor-beta can be blocked by
      estradiol. Female rat hepatocytes in primary culture were exposed to estradiol
      with and without various growth factors, and we determined DNA synthesis by
      measuring [3H]thymidine incorporation into extracted DNA or by determining the
      nuclear labeling index by means of autoradiography. The results show that
      estradiol, like ethinyl estradiol, has comitogenic activity for epidermal growth
      factor, although it is somewhat less potent. Four complete hepatic mitogens
      showed different abilities to stimulate DNA synthesis, with hepatocyte growth
      factor > transforming growth factor-alpha > epidermal growth factor > acidic
      fibroblast growth factor. Estradiol enhanced DNA synthesis occurring in response
      to all four of these complete hepatic mitogens. This finding suggests that the
      mechanism of estrogen comitogenesis may involve effects at a point where the
      different signal-transduction pathways leading from the growth factors converge.
      The level of estrogen-mediated enhancement of DNA synthesis was similar for all
      four mitogens, ranging from 1.5 to 2.2-fold, depending on the experiment.
      Furthermore, determination of the nuclear labeling index showed that estrogen
      enhancement of DNA synthesis was associated with an increase in the percentage of
      hepatocytes that responded to the growth factors. Finally, estradiol did not
      specifically block the growth-inhibitory effects of transforming growth factor
      beta.

PMID- 7506226
TI  - The search for the ultimate screening test for hepatocellular carcinoma
      continues.

PMID- 7506225
TI  - A multicenter randomized controlled trial of recombinant interferon-alpha 2b in
      patients with acute transfusion-associated hepatitis C.
AB  - To assess whether interferon-alpha might prevent non-A, non-B hepatitis from
      becoming chronic, 45 consecutive patients with transfusion-associated hepatitis
      were enrolled in a randomized clinical trial. Thirty-eight patients had hepatitis
      C virus infection, and 7 had non-A, non-B, non-C hepatitis. Twenty-six patients
      (22 with HCV) were given 3 MU of recombinant interferon-alpha 2b three times a
      week for 12 wk, whereas 19 (16 with HCV) were not. Biochemical and virological
      parameters were monitored at regular intervals during an 18-mo follow-up. At the
      end of the 3-mo therapy, 16 (73%) patients with hepatitis C had normal serum ALT
      activity, compared with 7 (44%) who were not treated (NS). Fifty-three percent of
      the treated patients and none of the untreated patients had normal ALT levels and
      no HCV RNA (p = 0.0087). At the end of the 18-mo follow-up, 13 (59%) treated
      patients had normal ALT levels, compared with 6 (37%) untreated controls (NS).
      Thirty-nine percent had normal ALT and no HCV RNA, compared with none of the
      controls (p = 0.035). Four patients (22%) had had sustained complete responses to
      interferon, defined as normal ALT levels and no HCV RNA at the end of the 3-mo
      treatment period and the 18-mo follow-up period. All seven patients with non-A,
      non-B, non-C hepatitis, treated and untreated, recovered uneventfully from
      hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506227
TI  - Prospective study of alpha-fetoprotein in cirrhotic patients monitored for
      development of hepatocellular carcinoma.
AB  - The usefulness of measurements of serum alpha-fetoprotein elevation for diagnosis
      of the development of hepatocellular carcinoma was evaluated by a prospective
      study of 260 patients with cirrhosis. Hepatocellular carcinoma was found in 55
      patients during the 5-yr follow-up, excluding 7 found to have hepatocellular
      carcinoma in the first 6 mo. The cumulative incidence of hepatocellular carcinoma
      was 26% in the 185 patients who had alpha-fetoprotein levels below 20 ng/ml at
      the time of entry and 46% in the 68 patients who had alpha-fetoprotein levels of
      20 ng/ml or more but below 200 ng/ml. In 169 of the patients, serum levels of
      alpha-fetoprotein were assayed regularly for at least 2 yr. The incidence of
      hepatocellular carcinoma development in the 36 patients who had repeated
      transient increases in alpha-fetoprotein to above 100 ng/ml was 36%. This was
      significantly higher than the incidence in the 99 patients who had alpha
      fetoprotein levels consistently below 20 ng/ml. Thus patients who had alpha
      fetoprotein levels of 20 ng/ml or more, who had transient increases in alpha
      fetoprotein or who had both should be treated as being in a super-high-risk group
      for hepatocellular carcinoma. Frequent and careful examination by ultrasonography
      of such patients is recommended.

PMID- 7506228
TI  - Halomethane-chlordecone (CD) interactive hepatotoxicity--current concepts on the
      mechanism.
AB  - Why is a low dose of toxic chemical nontoxic? What makes a larger dose of the
      same chemical toxic? Extensive work done to understand the mechanism of
      halomethane hepatotoxicity and its potentiation by chlorinated insecticide,
      chlordecone has resulted in the understanding of these basic tenets of
      toxicology. Studies suggest that ordinarily a small dose of halomethane causes
      limited liver injury which is accompanied by stimulated tissue repair enabling
      complete recovery from injury before manifestation. A large dose of halomethane
      becomes toxic due to suppressed tissue repair, which permits injury to progress
      in an unchecked fashion. Exposure to very low levels of chlordecone results in
      highly exaggerated toxicity of ordinarily nontoxic doses of halomethane because
      of suppressed hepatocellular regeneration and restoration, permitting the
      progression of liver injury ultimately resulting in liver failure and animal
      mortality. This concept is further supported by the observation that, while
      exposure to even high levels of phenobarbital and subsequent low nontoxic doses
      of halomethane results in greater level of initial liver injury, tissue repair is
      not completely suppressed; it is slightly postponed by 24 hr, but then much
      higher rate of tissue repair ensures and consequently enables the animals to
      completely recover from liver injury and survive. Thus, whether initiation of
      tissue repair processes occurs or not is the critical determinant in the ultimate
      manifestation of hepatotoxicity and its end result of either animal death or
      recovery and survival. Currently understood 'Mechanisms of toxicity' adequately
      explain only how toxic injury begins. These mechanisms do not permit us to
      predict the ultimate outcome of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506229
TI  - Lysine- and threonine-sensitive aspartokinase isoenzymes from spinach leaves
      share common antigenic determinants.
AB  - The lysine- and threonine-sensitive isoenzymes of aspartate kinase were purified
      to homogeneity from spinach leaves and polyclonal antibodies were raised in
      rabbits. The antibodies were characterized by various immunological tests like
      Ouchterlonys-double-diffusion, titrations of the inhibition of enzyme activity
      and ELISA. The antibodies against the lysine-sensitive isoenzyme could recognise
      as little as 50 ng of the pure antigen protein and that against the threonine
      sensitive form could recognise 200 ng of the protein in the ELISA tests. The
      immunological tests have also shown that the lysine and threonine sensitive
      isoenzymes of aspartate kinase share some common antigenic determinants and
      differ in others.

PMID- 7506230
TI  - Improved presentation of antigenic sites in enzyme-linked immunosorbent assay:
      antigenicity of reduced and carboxymethylated riboflavin carrier protein.
AB  - Disulphide reduced and carboxymethylated riboflavin carrier protein (RCM-RCP), an
      unfolded derivative of chicken RCP, does not bind riboflavin and there is a
      drastic reduction in its ability to interact with antiserum to cRCP. Antibodies
      to RCM-RCP are directed against sequential epitopes(s). On radioiodination of RCM
      RCP, a maximum of 30-50% binding at dilution of 1:500 was obtained with rabbit
      antibodies RCM-RCP [n = 5]. However, high titer antibodies was obtained when
      radioiodinated RCM-RCP was immobilized on ELISA microtiter plates suggesting that
      immobilization of RCM-RCP leads to either preservation of antigenic sites or
      improved presentation of the antigenic determinants. An avidin-biotin system was
      utilized to develop an ELISA.

PMID- 7506232
TI  - Human alpha 2-macroglobulin and its biological significance.
AB  - The review deals with an important plasma protein viz. alpha 2-macroglobulin,
      which is a wide-spectrum proteinase-inhibitor and can bind covalently with
      certain growth factors. Unlike other plasma proteinase-inhibitors, the alpha 2M
      proteinase complex remains active towards low mol. wt synthetic substrates. Human
      alpha 2M contains an internal thiol ester and the disulphide bridged dimer of the
      complex appears to be the functional unit of alpha 2M. The potentially harmful
      complexes are cleared by the receptor-mediated mechanism in the
      reticuloendothelial system. Rapid clearance of the active complex from the
      circulation indicates its importance in controlling proteolytic activity. It is a
      potent immunoregulator. A number of immunologically important reactions involve a
      protease-dependent step, which could be modified by alpha 2M. The tumor
      associated alpha 2M may have a role in the biology of tumor cells.

PMID- 7506231
TI  - Impact of protein deficiency and exposure to hexachlorocyclohexane or malathion
      on lipid metabolism in pregnant rats.
AB  - Dietary intake of three oral doses of hexachlorocyclohexane (HCH) (60 mg/kg body
      wt) or malathion (500 mg/kg) by normal and protein-deficient diet fed pregnant
      rats on the 6th, 10th and 14th day of gestation resulted in the impairment of
      lipid metabolism, viz. hypercholesterolemia and hypertriglyceridemia. The
      cholesterol, triglyceride and phospholipid contents in serum, brain, liver,
      kidney and uterus were increased significantly by HCH and malathion exposure,
      irrespective of the protein content in the diet. The incorporation of [1,2
      14C]acetate into the hepatic lipids was stimulated by both HCH and malathion,
      suggesting a higher rate of lipid synthesis in the liver of normal and protein
      deficient diet fed dams. The low protein content in the diet intensified the
      pesticide-induced changes and more severe alterations were noticed in HCH exposed
      dams than in malathion exposed dams.

PMID- 7506233
TI  - Characterization of a novel IRF-1-deficient mutant cell line.
AB  - The transcriptional activation of the major histocompatibility complex (MHC)
      class I genes by both type I (alpha/beta) and II (gamma) interferons (IFNs) has
      been extensively studied, and it has been shown that the upregulation of several
      DNA-binding proteins is critical for this process. In our laboratory, we
      introduced the mouse H-2Kb gene into the AKR mouse leukaemia cell line K36.16 to
      effect the generation of tumor-specific immunity. Individual clones were selected
      and studied. Whereas the MHC class I genes in most of the clones obtained could
      be stimulated by interferons, one of the clones obtained, clone Kb-S27, failed to
      be induced, or was at best poorly induced by IFN-alpha/beta and -gamma. Both the
      exogenous H-2Kb and the endogenous H-2Dk genes behaved in the same manner and
      were not stimulated by IFNs. The lack of response to IFNs by clone Kb-S27 also
      resulted in its resistance to the antiproliferative effects of IFNs. This lack of
      IFN-induction by clone Kb-S27 was not simply due to a change in its surface
      interferon receptors. Gel-retardation assay and northern blot analysis both
      demonstrated the lack of induction of the IRF-1 DNA-binding factor in clone Kb
      S27. In addition, northern blot analysis showed that the IRF-2 gene expression in
      clone Kb-S27 was upregulated when compared with the other IFN-inducible clones.

PMID- 7506234
TI  - Characterization of immunoglobulin heavy chain variable regions in the Mexican
      axolotl.

PMID- 7506235
TI  - Cellular expression and tissue distribution of the human LAG-3-encoded protein,
      an MHC class II ligand.

PMID- 7506236
TI  - Diagnostic value of maternal serum alpha fetoprotein for predicting pregnancy
      outcome in high risk pregnancies: an epidemiological perspective.
AB  - This study was conducted on high risk pregnancies, between 6-40 weeks of
      gestation, to evaluate the difference in maternal serum alphafetoprotein (MSAFP)
      levels in normal and abnormal pregnancies. It's predictive value for pregnancy
      outcome was calculated. Age and parity matched, normal pregnant women with normal
      pregnancy outcome were taken as controls. It was determined that the overall
      sensitivity (75.6%) and specificity (83.7%) was not very good for diagnostic
      purposes. On the contrary in patients with neural tube defects, congenital
      anomalies, early pregnancy complications leading to fetal death, still birth,
      neonatal deaths, Rh incompatibility and preterm deliveries the specificity was
      (96%-100%), due to very few false positives but sensitivity was comparatively low
      (75%-89%) due to many false negatives. As a result the predictive value of a
      negative test in these conditions was very high (80%-100%), though that of a
      positive test was comparatively low (60%-89%). This establishes a diagnostic
      value of MSAFP, especially in high risk pregnancies as opposed to its use as a
      screening test for all pregnancies. This is of special value for a poor country
      like India, where it is not possible to screen total pregnant population due to
      economic and logistic reasons.

PMID- 7506237
TI  - The construction of patienthood in medical advertising.
AB  - The purpose of this study was to investigate the dominant symbolic elements,
      themes, and discourses used in drug advertisements published in a weekly magazine
      directed toward physicians. The discussion is concerned with both the visual
      signs and textual format of the advertisements, analyzing their attempts to
      create images around the drugs that appeal to the medical readership of the
      magazine. With the premise that the producers of the advertisements drew upon
      shared knowledge and belief systems of their medical audience to create a
      meaningful image for the drugs, the focus of the article is upon the portrayal of
      patients in the advertisements, with particular interest in gendered
      representations. The author argues that the way in which patients are portrayed
      visually and verbally in such advertisements is revealing of the ideological
      dimension of the doctor-patient relationship within the biomedical system of
      healing, including notions of the mechanical man and the vulnerable woman as
      archetypal patients.

PMID- 7506238
TI  - Isovolemic hemodilution and pancreatic islet blood flow in the rat.
AB  - Adult rats were isovolemically hemodiluted with isotonic dextran-solutions to
      reduce the hematocrit by approximately one third. This procedure decreased the
      mean arterial blood pressure but markedly increased cardiac output. The serum
      glucose concentration was increased, whilst the serum insulin concentration
      remained unchanged. The blood flow values and the vascular conductances of both
      the whole pancreas and the islets were reduced by 40-60% by hemodilution.
      However, the decrease in islet blood flow was less affected as indicated by the
      increase in the percentage fraction of whole pancreatic blood flow diverted
      through the islets (13.5 +/- 0.7% compared to 9.7 +/- 0.8%; p < 0.05). It is
      concluded that isovolemic hemodilution, despite a markedly increased cardiac
      output, decreased both whole pancreatic blood flow and islet blood flow.

PMID- 7506240
TI  - Experience with a new intraurethral stent for high-risk patients with benign
      prostatic hypertrophy.
AB  - Eight patients with benign prostatic hypertrophy (BPH), considered as a high risk
      for an operation because of severe accompanying disease, were treated with a self
      retaining intraurethral catheter set. Two patients were judged unfit for
      operation (one because of severe cardiac failure, the other because of severe
      respiratory failure) and 1 patient rejected an operation. The BPH surgery was
      postponed in the others because of recent operations for such diseases as gastric
      cancer or because of severe gastric ulcer. All patients voided freely after stent
      placement and were continent. The device was left in place for 1 to 16 weeks. The
      chief complaint was frequency of voiding, with intervals of 1 to 2 hours. Some
      micturition discomforts such as urgency were recognized in 2 patients, but
      disappeared within 1 to 2 days. Pyuria observed before treatment disappeared in
      all but 1 patient. Average residual urine volume calculated on ultrasonograms was
      54 ml. Stone formation was demonstrated in 1 patient 9 weeks after placement. We
      concluded that the intraurethral stent is an effective device for high-risk
      patients with BPH. However, a longer follow-up study will be needed to exclude
      late side effects.

PMID- 7506239
TI  - The use of intermittent chlorhexidine bladder irrigation in the prevention of
      post-prostatectomy infective complications.
AB  - The efficacy of peri-operative intermittent bladder irrigation with 0.05%
      chlorhexidine gluconate solution in the prevention of post-prostatectomy
      infective complications was assessed in men with pre-operative indwelling urinary
      catheters. Thirty-two consecutive patients undergoing transvesical prostatectomy
      were randomly allocated to the test group (chlorhexidine irrigation) and control
      group (saline irrigation). Pre-operatively, intermittent chlorhexidine bladder
      irrigation achieved sterile urine in only 3 of 13 patients, in the rest
      bacteriuria persisted. However, the irrigation was able to reduce significantly
      (P < 0.05) the incidence of intra-operative bacteraemia and severe wound
      infection. Furthermore, septicaemia was absent and post-operative urinary
      catheter requirements and hospital stay were shortened. Histology of bladder
      mucosal biopsies revealed that 0.05% chlorhexidine used on intermittent basis
      caused no injuries.

PMID- 7506241
TI  - Prostatic melanosis.
AB  - Melanosis of the prostate gland is a rare pathological finding. Its clinical
      significance is unknown and the histogenesis is occult. It is found in benign
      prostatic hyperplasia or carcinoma of the prostate. We present such a case and
      review the literature.

PMID- 7506242
TI  - Cisplatin, vinblastine and bleocin in the treatment of disseminated testicular
      cancer.
AB  - Fifty-nine stage IV disseminated testicular cancer patients underwent 5 or more
      courses of cisplatin, vinblastine and bleocin (PVB) chemotherapy from August 1981
      to July 1989. Tumour histology included 15 seminomas, 13 embryonal carcinomas, 13
      teratocarcinomas and 18 mixed tumours. Thirty-four patients (58%) achieved
      complete remission with an average duration of 56+ months (range 3 to 113+), and
      12 patients (20%) achieved partial remission with an average duration of 8.5
      months (range 2 to 33). The overall response rate was 78%. Four patients achieved
      complete remission after adjunctive surgery. The best response was obtained in
      seminoma patients (73% complete remission). The 5-year survival is 88% for
      complete responders, 10% for partial responders, and 53% overall. The PVB
      combination has considerably improved the survival of disseminated testicular
      cancer patients, but the low survival rate in poor-risk patients necessitates
      more aggressive chemotherapy regimens.

PMID- 7506243
TI  - Comparison of T1-enhancing and magnetic susceptibility magnetic resonance
      contrast agents for demarcation of the jeopardy area in experimental myocardial
      infarction.
AB  - RATIONALE AND OBJECTIVES: This study compared the areas demarcated by a T1
      enhancing agent, Gd-DTPA-BMA, and a magnetic susceptibility agent, Dy-DTPA-BMA,
      with 201thallium autoradiography (indicator of perfusion) and postmortem
      histochemical staining with triphenyltetrazolium chloride (TTC)(indicator of
      infarction). METHODS: Thirteen rats were subjected to coronary artery occlusion
      for 3 to 4 hours before acquisition of four sets of electrocardiogram-gated spin
      echo magnetic resonance (MR) images: T1-weighted images before and after 0.2
      mmol/kg Gd-DTPA-BMA; and T2-weighted images before and after 0.3 mmol/kg Dy-DTPA
      BMA. After MR imaging, intravenous 201thallium delineated the area of decreased
      myocardial perfusion. At autopsy, TTC staining delineated the area of myocardial
      infarction. RESULTS: A myocardial region in the distribution of the occluded
      artery was delinated as a hyperintense area ("hot-spot") by Dy-DTPA-BMA and as a
      hypointense area ("cold-spot") by Gd-DTPA-BMA. The hyperintense area demarcated
      by Dy-DTPA-BMA (51 +/- 3% of the area of the midequitorial slice of the left
      ventricle) showed a closer relationship to the area of decreased myocardial
      perfusion (jeopardized area) (46 +/- 3%), determined by 201thallium
      autoradiography, than the area of myocardial infarction (36 +/- 4%), determined
      by histochemical staining. However, the hypointense area demarcated by Gd-DTPA
      BMA (29 +/- 2%) did not relate as closely to the area of decreased myocardial
      perfusion (slope = 0.54) or the area of myocardial infarction (r = 0.46).
      CONCLUSIONS: The abnormal myocardial area delineated by the magnetic
      susceptibility agent showed a closer relationship to the area of deficient
      myocardial perfusion (jeopardy area) after coronary occlusion than that defined
      by T1-enhancing contrast media.

PMID- 7506244
TI  - [Persistent pruritus after hydroxyethyl starch infusions. Retrospective long-term
      study of 266 cases].
AB  - In 266 patients receiving hydroxyethyl starch (HES) for otological indications,
      we retrospectively analysed the incidence of pruritus and its relationship to
      clinical and therapeutic parameters. We found that 32% of the patients developed
      pruritus, which characteristically appeared as pruritic crises. In 55% of
      pruritic patients onset after the HES medication had already been discontinued
      was reported. The symptoms persisted on average for 8.8 weeks. Pruritus was
      generalized, but with a predilection for the trunk and genitalia. Coincidental
      atopic disease or higher age did not promote pruritus. However, the incidence of
      pruritus correlated well with the cumulative dosage and also depended on the type
      and molecular weight of HES given (6% or 10%, mol.wt. 40 or 200 kDa). Light and
      electron microscopic assessment showed deposits of HES, especially within dermal
      macrophages and endothelial cells and adjacent to nerve fibres. Pathogenetically
      a histamine-independent pathway is probably responsible for the induction of
      pruritus. Hence, classic antihistaminic drugs had no therapeutic effect in our
      patients.

PMID- 7506245
TI  - Combined Ki-67 and Feulgen stain for morphometric determination of the Ki-67
      labelling index.
AB  - In this note we present a combined Ki-67 and Feulgen stain for morphometric
      determination of the Ki-67 labelling index. The immunohistochemical part of this
      double staining technique is based on the alkaline-phosphatase-anti-alkaline
      phosphatase (APAAP) method, visualizing the enzyme activity by the nitro-blue
      tetrazolium chloride (NBT)/bromo-chloro-3-indolyl-phosphate (BCIP) technique. The
      NBT/BCIP complex resists the hydrolytic activity of the Feulgen stain. The
      staining method presented allows semi-automatic determination of both the total
      nucleus-area as well as the Ki-67 positive nucleus-area using a morphometric
      computer system. The Ki-67 labelling index thus achieved is based on the relative
      nuclear area of Ki-67 positive nuclei and is clearly more precise and efficient
      than the counting method using an ocular grid.

PMID- 7506246
TI  - Development of substance P and neurokinin A immunoreactivity in ganglia supplying
      nerves to the submandibular glands of the rat.
AB  - Developing submandibular, trigeminal and superior cervical ganglia, which provide
      innervation to the submandibular glands, were studied for substance P (SP)- and
      neurokinin A (NKA)-immunoreactive (IR) ganglion cells and nerve fibres in rat.
      These ganglia were examined by using an indirect immunofluorescence technique at
      daily intervals from the 16th day in utero (i.u.) until birth, and subsequently
      on the 2nd, 5th, 7th, 12th, 16th, 30th, 42nd postnatal day and in the adult (3
      months). In the submandibular ganglion SP- and NKA-IR cells and fibres first
      appeared in considerable numbers on the 19th day i.u. (in one sample out of five
      on the 18th day i.u.), when more than 90% of the ganglion cells were
      immunoreactive to SP and NKA. The number stayed at more than 90% to the 7th
      postnatal day and then slowly decreased to the levels of adult animals (18% SP,
      17% NKA). The first SP- and NKA-IR ganglion cells and fibres appeared in the
      trigeminal ganglion on the 18th day i.u. when they represented 7% (SP) and 4%
      (NKA) of the ganglion cells. The number of SP- and NKA-IR cells increased
      steadily, reaching a maximum at the time of birth when 68% (SP) and 74% (NKA) of
      the ganglion cells were immunoreactive. Thereafter they began to decrease toward
      the level of an adult rat (10% SP, 11% NKA). In the superior cervical ganglion
      only a few SP- and NKA-IR ganglion cells were detected from the 19th day i.u. to
      the fifth postnatal day. Positive ganglion cells were also occasionally found in
      the nerve trunks outside the superior cervical ganglion.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7506247
TI  - Effect of filgrastim (G-CSF) in Hodgkin's disease patients treated with radiation
      therapy.
AB  - PURPOSE: To evaluate the effect of filgrastim (recombinant human G-CSF) on
      radiation-induced neutropenia in a well defined, homogenous patient population.
      METHODS AND MATERIALS: Seven patients who were to receive large field
      subdiaphragmatic irradiation after thoracic "mantle" fields for treatment of
      Hodgkin's disease entered this study. They received daily subcutaneous (SC)
      injections of filgrastim during subdiaphragmatic irradiation. Total white blood
      cell (WBC) and absolute neutrophil cell (ANC) counts were measured and compared
      to a historical series of patients, and hematological toxicity was assessed. The
      endpoints of the study were nadir WBC and ANC counts and time to WBC and ANC
      recovery. RESULTS: Compared to the historical series, filgrastim significantly
      increased the WBC and ANC throughout the period of subdiaphragmatic irradiation.
      Nadir WBC (5.98 +/- 1.24/mm3) and ANC (4.71 +/- 1.07/mm3) in the Filgrastim group
      were approximately two times those of the historical series (3.32 +/- 1.06/mm3
      and 2.39 +/- 0.97/mm3 respectively; p < 0.002). Nadir platelet counts were not
      affected by filgrastim therapy. Three of seven patients reported mild
      musculoskeletal pain, but there was no other apparent toxicity. CONCLUSION:
      Compared to the historical series, filgrastim therapy significantly increased WBC
      and ANC during extended field radiation therapy and was well tolerated. It may be
      clinically useful in other groups of patients who are likely to develop profound
      neutropenia during large field irradiation.

PMID- 7506249
TI  - Electron-probe analysis of isolated goldfish hair cells: implications for
      preparing healthy cells.
AB  - Electron-probe analysis provides an objective criterion for the physiological
      status of cells: whether they show the high potassium and low sodium that are
      expected of healthy animal cells. Preparing isolated goldfish hair cells that
      were healthy by this criterion required several precautions, including: limited
      exposure to enzymes and to simple salt solutions, a rest period between enzyme
      treatment and mechanical disruption of the tissue, and presence of bovine albumin
      in the medium both during the rest period and during mechanical dispersion and
      plating. Cells prepared with these precautions from the saccule and lagena and
      kept in an enriched medium had the following elemental composition (mole
      percentages with respect to phosphorus): K, 103; Na, 18; Cl, 23; S, 13; Mg, 8;
      Ca, 1.5. These mole percentages were close to these elements' total millimolar
      concentrations in the cells. If the precautions were not taken, cells with intact
      surface membranes (as assessed by exclusion and retention of dyes) could be
      obtained, but the cells had elevated cell sodium and low cell potassium.

PMID- 7506250
TI  - Frequent fusion of liposomes to a positively charged planar bilayer without
      calcium ions.
AB  - A novel positively charged planar bilayer membrane was formed from a mixture
      containing 20% cationic lipid, 1,2-dioleoyloxy-3-(trimethylammonio)propane, and
      neutral phospholipid mixture of 56% phosphatidylethanolamine and 24% egg
      phosphatidylcholine. The basic properties of the bilayer were essentially the
      same as those previously reported for neutral and negatively charged lipid
      bilayers. Using the positively charged bilayer in addition to neutral and
      negatively charged bilayers, the effects of charge of the planar bilayers upon
      vesicle-planar membrane fusion were investigated by measuring the fusion, to the
      bilayers, of liposomes containing nystatin-ergosterol channels and carrying a net
      negative charge. The tendency for fusion was evaluated in terms of the time
      elapsed before the first fusion event (denoted fusion time). In the absence of
      calcium ions, a fusion time of about 1 min was measured with the positively
      charged planar bilayers, and about 5 and over 15 min with the neutral and
      negatively charged planar bilayers, respectively. These results indicated that
      the vesicle-planar membrane fusion without calcium ions is greatly enhanced by
      the presence of cationic lipids in the planar bilayers, and suggested the
      usefulness of cationic lipid bilayers.

PMID- 7506248
TI  - Characterization of the promoter region of the human c-kit proto-oncogene.
AB  - The c-kit proto-oncogene encodes a tyrosine kinase receptor for stem cell factor
      and plays a critical role in the growth and differentiation of various types of
      cells including hematopoietic stem cells. To investigate the mechanisms of its
      transcriptional regulation, we isolated the 5' flanking region of the human c-kit
      gene and characterized its promoter activity in hematopoietic cells. Nucleotide
      sequence analysis revealed that the 1.2 kb 5' flanking region lacked a typical
      "TATA box," but had a relatively high G + C content and four potential Sp1
      binding sites. Putative binding sites for AP-2, basic helix-loop-helix proteins,
      Ets-domain proteins, Myb and GATA-1 were also found. Primer extension and S1
      nuclease protection analyses of hematopoietic cells indicated that the major
      transcription start sites are 62 bp and 58 bp upstream of the translation start
      site. Essentially the same start sites were detected in non-hematopoietic cells
      such as small cell lung carcinoma and glioblastoma: this single promoter in c-kit
      is different from the multiple promoter system of c-fms, a c-kit-related gene, in
      which at least two promoters are differently used in hematopoietic and non
      hematopoietic cells. An analysis of the c-kit 5' flanking region using the
      bacterial chloramphenicol acetyltransferase gene (CAT assay) in human
      erythroleukemia HEL cells, which express the endogenous c-kit mRNA at high
      levels, showed that a region from -180 to -22 is important for the expression of
      the c-kit gene. In addition, a negative regulatory element(s) is suggested to be
      involved in the regulation of the c-kit gene expression in mammals.

PMID- 7506251
TI  - Hamster alpha-macroglobulin and murinoglobulin: comparison of chemical and
      biological properties with homologs from other mammals.
AB  - alpha-Macroglobulin and murinoglobulin were purified to homogeneity from Syrian
      hamster plasma and their properties were compared with those of their respective
      homologs from other mammals. The trypsin-inhibiting capacity of hamster
      murinoglobulin was much weaker than those of rat and mouse murinoglobulins.
      Hamster alpha-macroglobulin was cleaved by trypsin at a number of sites whereas
      the human homolog was split essentially only in a "bait" region into two
      fragments of similar size. Hamster alpha-macroglobulin treated with methylamine
      differed from that treated with trypsin in the electrophoretic mobility,
      intensity of fluorescence induced by binding of bis(8-anilino-1
      naphthalenesulfonate), and plasma clearance pattern, whereas virtually no
      difference was observed between the human homologs treated in the same manner.
      The reaction of hamster alpha-macroglobulin with methylamine, as measured by the
      generation of thiol groups and the decrease in trypsin-protein amidase activity,
      was much slower than that of the human homolog. Trypsin in a complex with hamster
      alpha-macroglobulin retained its fibrinolytic activity, but this was not the case
      for human or rabbit alpha-2-macroglobulin. These results suggest that, compared
      with the human homolog, hamster alpha-macroglobulin is more loosely packed in the
      native state, undergoes conformational change more slowly on treatment with
      methylamine, and less efficiently hinders the access of proteinaceous substrates
      to trapped proteinase. The serum concentration of hamster alpha-macroglobulin was
      6.9 mg/ml, or about 3-fold higher than that of the human type, and showed little
      change during the acute-phase reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506252
TI  - The mechanism of human immunodeficiency virus reverse transcriptase-catalyzed
      strand transfer from internal regions of heteropolymeric RNA templates.
AB  - The mechanism of human immunodeficiency virus reverse transcriptase-catalyzed
      strand transfer synthesis (i.e. switching of the primer to a new template) from
      internal regions of natural sequence RNA was investigated. The system consisted
      of a 142-nucleotide RNA template (donor) primed with a specific 20-nucleotide DNA
      oligonucleotide used to initiate synthesis. DNA oligonucleotides with homology to
      internal regions of the donor were used as acceptor templates. In reactions
      performed in the absence of acceptor template, a prominent DNA synthesis product
      75 nucleotides in length resulting from pausing DNA synthesis within the homology
      zone was observed. Prominent donor RNA degradation products of 47 or 54
      nucleotides were also observed, in reactions with 80 or 150 mM KCl, respectively.
      The lengths indicated a potential 13- or 20-nucleotide long, respectively,
      complementary region between the DNA and RNAs. The 54-, but not the 47-,
      nucleotide RNA was susceptible to Escherichia coli RNase H, indicating that the
      DNA was annealed only to the 54-mer. When acceptor was added, a portion of the 75
      nucleotide DNA was chased into transfer product at both salt concentrations, and
      a portion of the 54-mer RNA became resistant to E. coli RNase H. Evidently, this
      donor RNA was annealed to the 75-nucleotide long DNA but could be actively
      displaced by the acceptor. Overall, these observations support two mechanisms for
      transfer. In one, the pause site-specific DNA dissociates from the donor template
      before transferring. In the other, the acceptor actively displaces the DNA from
      the donor.

PMID- 7506253
TI  - Activation of keratin 19 gene expression by a 3' enhancer containing an AP1 site.
AB  - We previously reported that the human keratin 19 (K19) gene was expressed in
      nonkeratinizing oral epithelial subtypes, and that the steady state K19 mRNA
      levels in different normal epithelial subtypes correlated with the levels of the
      retinoic acid receptor (RAR) beta-mRNA (Hu, L., Crowe, D. L., Rheinwald, J. G.,
      Chambon, P., and Gudas, L. J. (1991) Cancer Res. 51, 3972-3981). To elucidate the
      mechanisms by which the K19 gene is differentially expressed in various
      epithelial subtypes, we isolated phage containing human K19 genomic DNA from a
      human placental library. Through transient transfection assays with various
      K19/CAT constructs that contain different portions of K19 genomic DNA, an
      enhancer sequence has been identified in the K19 3'-flanking region. In normal
      human epithelial cell strains, the activity of this enhancer correlates with K19
      mRNA abundance. This enhancer activates both the K19 and TK basal promoters in
      HeLa cells. A high level of K19/CAT fusion mRNA was detected when this K19 3'
      enhancer sequence was present at the 3' end of the fusion gene whereas no K19/CAT
      fusion transcript was detected if this 3' K19 enhancer sequence was absent,
      suggesting that the 3' K19 enhancer is crucial for the positive regulation of K19
      expression. Deletion analysis has permitted the localization of the enhancer to a
      19-base pair sequence which contains an AP1 binding site (AGTCATCT). Point
      mutations within this AP1 site completely abolished K19 enhancer activity in HeLa
      cells. Co-transfections of a c-jun expression vector with K19/CAT reporter
      constructs demonstrated that c-jun was able to activate the K19 promoter via the
      3' K19 enhancer. Collectively, these data indicate that a cis-acting AP1 element
      and its associated trans-acting effector proteins regulate expression of lineage
      specific genes in epithelial cells.

PMID- 7506254
TI  - The Golgi guanosine diphosphatase is required for transport of GDP-mannose into
      the lumen of Saccharomyces cerevisiae Golgi vesicles.
AB  - The Saccharomyces cerevisiae Golgi lumenal guanosine diphosphatase is
      hypothesized to generate GMP which in turn allows entry of GDP-mannose into the
      lumen to serve as substrate for mannosylation of proteins and lipids. We have
      recently shown in studies in vivo that this GDPase is required for protein and
      sphingolipid mannosylation in the Golgi lumen of S. cerevisiae. We have now
      isolated Golgi-vesicles from wild type and gda1 null mutants (GDPase defective)
      and have found that the initial rate of GDP-mannose entry into mutant vesicles
      was 5-fold lower than into those of wild type. Because the concentration of GDP
      within vesicles is insufficient to inhibit Golgi lumenal mannosyltransferases and
      the null mutant vesicles are impaired in synthesis of Golgi mannoproteins, the
      above results demonstrate that the reduced availability of GDP-mannose in the
      null mutants is the cause for altered Golgi mannosylation of macromolecules.

PMID- 7506255
TI  - The somatic cell-specific low density lipoprotein receptor-related protein of the
      chicken. Close kinship to mammalian low density lipoprotein receptor gene family
      members.
AB  - Recently, the family of mammalian genes homologous to that for the low density
      lipoprotein (LDL) receptor has grown. One of the new family members, termed LDL
      receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2MR), is one
      of the largest cell surface proteins characterized to date. Its functions have
      been hypothesized to include the plasma clearance of chylomicron remnants and
      activated alpha 2-macroglobulin, as well as the local metabolism of complexes
      between plasminogen activators and their endogenous inhibitors. Here we describe
      the molecular characterization of an LRP/alpha 2MR expressed in chickens, which
      do not metabolize chylomicron remnants. This chicken protein is expressed in
      somatic tissues and is different from a second LRP/alpha 2MR exclusively
      expressed in growing ovarian follicles. The sequence of the somatic cell-specific
      chicken LRP/alpha 2MR, deduced from cloned full-length cDNA, shows 83% overall
      identity with human LRP/alpha 2MR. Important characteristic features of the
      modular protein are completely conserved; in particular, all cysteine residues
      align perfectly. The avian LRP/alpha 2MR is post-translationally cleaved in the
      same fashion as its human counterpart, and the resulting 515-kDa extracellular
      subunit binds Ca2+, alpha 2-macroglobulin, and vitellogenin. The results indicate
      that avian LRP/alpha 2MR genes have emerged from an ancestor designed to ensure a
      pivotal event in the reproduction of oviparous species, i.e. vitellogenesis, and
      that mammalian LRP/alpha 2MRs have acquired features required for functioning in
      plasma clearance of certain non-yolk proteins.

PMID- 7506256
TI  - Synthetic mimics of juxtaposed amino- and carboxyl-terminal peptide domains of
      human gamma interferon block ligand binding to human gamma interferon receptor.
AB  - The epitopes of two neutralizing antibodies (47N3-6 and 47N30A35) raised against
      rhuIFN-gamma each mapped both to amino-terminal regions (22-29 and 12-19,
      respectively) and to a carboxyl-terminal region 131-139, suggesting the
      juxtaposition of these two domains in the native protein. Three novel peptides
      were designed to mimic a conformation of rhuIFN-gamma that places the two regions
      in close proximity (discontinuous peptides 1 (15-21-GGG-132-138), 2 (15-29...111
      118...130-138), and 3 (15-21-CGPGC-130-138)), by bridging the amino- and carboxyl
      terminal regions of gamma interferon. Each discontinuous peptide inhibits
      biological or receptor binding activities with an IC50 of 15-50 microM and
      produces a neutralizing antibody when used as an immunogen. Neutralizing rabbit
      polyclonal antibody (P616) raised against discontinuous peptide 1 was used as
      immunogen to generate an anti-idiotypic response. This anti-idiotypic antibody
      inhibits receptor binding and recognizes soluble gamma interferon receptor on
      direct enzyme-linked immunosorbent assay. The anti-idiotypic response suggests
      that juxtaposed regions at the amino and carboxyl termini serve as the receptor
      ligand binding site of human gamma interferon.

PMID- 7506257
TI  - Location of a novel type of interpolypeptide chain linkage in the human protein
      HC-IgA complex (HC-IgA) and identification of a heterogeneous chromophore
      associated with the complex.
AB  - Protein HC (human complex-forming glycoprotein, heterogeneous in charge) is a
      member of the lipocalin superfamily of hydrophobic ligand-binding proteins. The
      quantitatively dominating blood plasma form of protein HC is a protein HC-IgA
      complex (HC-IgA), which is the fourth most abundant immunoglobulin species in
      plasma. A photodiode array detection system on-line with a high performance
      liquid chromatograph has allowed the identification of low amounts of a
      heterogeneous fluorescent chromophore covalently bound to HC-IgA, and displaying
      significant absorption in the visible region in resemblance to the free protein
      HC chromophore. Several structurally related chromophore-containing linked
      peptides, carrying 80% of the light absorption at 330 nm of HC-IgA, were isolated
      from a pepsin-produced protein HC-alpha 1-nonapeptide. Sequence analysis of these
      linked peptides demonstrated that the bond between protein HC and IgA represents
      a novel type of reduction-resistant linkage between polypeptide chains and
      involves the cysteine residue 34 of protein HC and the penultimate cysteine
      residue of the carboxyl-terminal part of one of the IgA heavy chains, as well as
      the heterogeneous fluorescent chromophore. The light absorption and fluorescent
      spectra of the chromophore-linked peptides were similar to those of native free
      protein HC.

PMID- 7506258
TI  - Activation of the cystic fibrosis transmembrane conductance regulator by cGMP in
      the human colonic cancer cell line, Caco-2.
AB  - Intestinal chloride (Cl-) secretion can be induced by the heat-stable enterotoxin
      (STa) from Escherichia coli via generation of cGMP. We investigated the
      regulatory pathway responsible for cGMP-mediated Cl- secretion in the human
      colonic carcinoma cell line Caco-2 using whole-cell voltage clamp techniques.
      Cyclic GMP or cAMP induced a 5-fold increase in Cl- conductance (gCl) in the
      presence of intracellular ATP and 3-isobutyl-1-methylxanthine. Current activation
      by cGMP persisted in the presence of the type I cGMP-dependent protein kinase
      (PKG) inhibitor, KT5823, but was inhibited by the specific peptide inhibitor of
      the cAMP-dependent protein kinase A (PKA), PKI5-24. The stimulatory effects of
      cGMP and cAMP on gCl were not additive. The cystic fibrosis transmembrane
      conductance regulator (CFTR) is a Cl- channel that is regulated by intracellular
      ATP and by cAMP-dependent phosphorylation. In order to determine whether CFTR was
      involved in the cGMP-dependent increase in gCl, we tested the effect of
      intracellularly injected anti-CFTR505-511 antibodies previously shown to inhibit
      CFTR function. Antibodies introduced into individual cells via the patch pipette
      completely inhibited cGMP-dependent current activation. Cyclic GMP also failed to
      activate gCl in cystic fibrosis cells. Taken together, these studies demonstrate
      that activation of the CFTR via PKA-dependent phosphorylation accounts for the
      cGMP-mediated increase in Cl- secretion in Caco-2 cells.

PMID- 7506260
TI  - A testis-specific promoter in the rat vasopressin gene.
AB  - In the rat testis, the vasopressin gene is transcribed into precursor RNAs that
      are processed into a number of mature transcripts. One of these transcripts has a
      structure identical to that of the hypothalamic RNA that encodes the vasopressin
      prepropeptide, but is present at such low levels that it can only be detected by
      the polymerase chain reaction. Other vasopressin-like RNAs are derived from
      differential splicing events that join transcribed sequences between 3 and 9
      kilobases upstream of the hypothalamic transcription start site to exons
      corresponding to II and III of the hypothalamic-type RNA. Here we describe the
      sequence of a testis-specific promoter and the exon structure of its
      transcription unit. We show that an in vitro synthesized RNA corresponding to the
      longer testicular vasopressin gene-derived transcript is not able to act as a
      template for protein synthesis in two different cell-free lysates. As attempts to
      localize the vasopressin-gene derived RNAs to particular cell types in the testis
      by in situ hybridization have consistently failed, we have used indirect methods.
      Three different procedures were used to effect germ cell depletion in adult male
      rats. Acute heat treatment of the testis, chronic ingestion of hydroxyurea, and
      chronic vitamin A deficiency all reduced the level of the aberrant testicular
      vasopressin-gene derived RNAs, indicating that their expression is closely
      associated with the integrity of germ cells and ongoing spermatogenesis.

PMID- 7506259
TI  - Purification and characterization of a collagen-degrading protease from
      Porphyromonas gingivalis.
AB  - A trypsin-like protease was purified from spent culture medium of oral pathogen
      Porphyromonas gingivalis by chromatography on columns of DEAE-Sepharose, gel
      filtration on Sephadex G-100, and chromatofocusing on PBE-94. Purified enzyme
      showed a single band on SDS-polyacrylamide gel electrophoresis with an estimated
      molecular weight of 55,000. Purified protease hydrolyzed type I, III, IV, and V
      collagen from human placenta, and type I collagen from rat tail and calf skin,
      but did not hydrolyze type II collagen from chicken sternal cartilage. The
      purified enzyme also hydrolyzed the C3 component of complement, fibrinogen,
      fibronectin, alpha 1-antitrypsin, alpha 2-macroglobulin, apotransferrin, and
      human serum albumin. The hydrolytic activity of the purified enzyme on
      chromogenic substrates was limited to substrates with arginine in the P-1
      position, although synthetic peptides were also cleaved at Lys-X linkage. The
      enzyme was activated by reducing agents dithiothreitol, L-cysteine, and
      glutathione and inhibited by cysteine protease inhibitors N-ethylmaleimide,
      iodoacetic acid, and iodoacetamide. The enzyme was also inhibited by trans
      epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64), leupeptin, antipain,
      salivary histidine-rich protein (HRP-5), soybean trypsin inhibitor, and EDTA.
      Since the protease is able to degrade the connective tissue components of
      periodontal tissue as well as components of host defense mechanism, this enzyme
      may be a potent virulence factor of P. gingivalis involved in invasion and tissue
      destruction.

PMID- 7506261
TI  - Purification and reconstitution of the high-conductance, calcium-activated
      potassium channel from tracheal smooth muscle.
AB  - The high-conductance Ca(2+)-activated K+ (maxi-K) channel from bovine tracheal
      smooth muscle was purified to apparent homogeneity by a combination of
      conventional chromatographic techniques and sucrose density gradient
      centrifugation. Fractions with the highest specific activity for binding of
      monoiodotyrosine charybdotoxin, [125I]ChTX, were enriched approximately 2000-fold
      over the initial digitonin-solubilized material up to a specific activity of 1
      nmol/mg protein. Silver staining after SDS-polyacrylamide gel electrophoresis of
      the fractions from the last step of the purification indicates that binding
      activity is correlated with a major component of the preparation that displays an
      apparent molecular weight of 62,000. Labeling the same preparation with 125I
      Bolton-Hunter reagent reveals the existence of both 62 (alpha)- and 31 (beta)-kDa
      subunits, in an apparent stoichiometry of 1:1, comigrating with binding activity.
      The beta subunit is heavily glycosylated. Deglycosylation studies indicate that
      the beta subunit represents the protein to which [125I]ChTX is covalently
      incorporated in the presence of the bifunctional cross-linking reagent
      disuccinimidyl suberate. Binding of [125I]ChTX to the purified ChTX receptor
      displayed the same pharmacological profile that has been found previously for
      toxin binding to native membranes, including inhibition by iberiotoxin,
      limbatustoxin, tetraethylamonium, potassium, cesium, and barium. The purified
      preparation was reconstituted into liposomes which were then fused with
      artificial lipid bilayers. Single channels were readily observed with a
      conductance of 235 picosiemens in 150 mM KCl that displayed selectivity for
      potassium over chloride and that were blocked by ChTX. The open probability of
      these channels was increased by depolarizing membrane potentials and by raising
      the internal calcium concentration. These data suggest that the maxi-K channel
      purified from tracheal smooth muscle is composed of two subunits.

PMID- 7506262
TI  - Osteopontin inhibits induction of nitric oxide synthase gene expression by
      inflammatory mediators in mouse kidney epithelial cells.
AB  - We report that osteopontin (OPN), a secreted, Arg-Gly-Asp-containing
      phosphoprotein expressed at high levels in the kidney, suppresses nitric oxide
      (NO) synthesis induced by the inflammatory mediators gamma-interferon and
      lipopolysaccharide in primary mouse kidney proximal tubule epithelial cells.
      Northern blot and immunofluorescence analyses of inducible nitric oxide synthase
      (iNOS) expression revealed that the inflammatory mediators increased iNOS mRNA
      and protein levels. Recombinant human OPN (purified from both mammalian cells and
      from Escherichia coli) inhibited this response by a process that was blocked by
      anti-OPN antiserum and by the peptide GRGDS, but not GRGES. The data suggest that
      inhibition of NO synthesis by OPN in these kidney cells is mediated by an
      integrin, possibly the alpha v beta 3 integrin, which is known to be an OPN
      receptor. NO is believed to control blood flow through the glomerulus, regulating
      salt and water balance, and to be important as a defense against tumor cells and
      infecting microorganisms. The ability of OPN to inhibit the induction of iNOS
      suggests that OPN may be an important regulator of the NO signaling pathway and
      NO-mediated cytotoxic processes.

PMID- 7506263
TI  - A computer-assisted analysis of conserved residues in the three-dimensional
      structures of the polymerase domains of Escherichia coli DNA polymerase I and HIV
      1 reverse transcriptase.
AB  - Using a computer-assisted molecular modeling protocol, we have completed the
      three-dimensional structures of HIV-1 reverse transcriptase and the Klenow
      fragment of DNA polymerase I based on the C alpha crystal coordinates of the
      individual enzymes. The two model-built structures were then used to compare the
      electrostatic potential contours and analyze the spatial positions of residues
      conserved in the catalytic domains of the two enzymes. In spite of rather weak
      sequence similarity and different folding patterns between the DNA-dependent DNA
      polymerase (pol I) and the RNA-dependent DNA polymerases (RT), we have noted the
      occurrence of identical or similar residues at common spatial positions in pol I
      and RT in a three-dimensional context. The homologous residues present at
      equivalent spatial position in the Klenow fragment and the p66 subunit of HIV-1
      RT may therefore imply their functional similarity. Furthermore, these conserved
      residues may represent a similar structure-function feature in all polymerases.

PMID- 7506264
TI  - Antigen-specific deletion of cloned T cells using peptide-toxin conjugate
      complexed with purified class II major histocompatibility complex antigen.
AB  - In a previous report, we showed that cloned T cells incubated with soluble,
      cognate major histocompatibility complex (MHC) II-peptide complex internalized
      the peptide moiety of the complex. Here, we report antigen-specific deletion of
      cloned T cells by treatment with soluble, cognate MHC II-(peptide-toxin)
      complexes. Toxin (doxorubicin or mycophenolic acid) was attached to synthetic
      AcMBP(1-14)Ala4 peptide, an analog of the natural acetylated NH2-terminal
      segment, AcMBP(1-14), of rat myelin basic protein (MBP). IAk-restricted, AcMBP(1
      14)-Specific AJ1.2 and 4R3.9 cloned murine T cells were killed by IAk-(AcMBP(1
      14)Ala4-toxin). No killing resulted from incubating AJ1.2 and 4R3.9 cells with
      irrelevant MHC II-(peptide-toxin) or treating IEk-restricted, pigeon cytochrome c
      specific A.E7 cloned murine T cells with IAk-(AcMBP(1-14)Ala4-toxin). T cell
      receptor-mediated T cell uptake of the peptide-toxin moiety of relevant complex
      was blocked by anti-T cell receptor-alpha/beta antibody and by excess toxin-free
      complex. LD50 determinations revealed that cognate MHC II-(peptide-toxin) killed
      T cells much more effectively than did peptide-toxin conjugate alone. Finally, T
      cell uptake of peptide-toxin and intracellular release of toxin occurred after
      incubation with relevant MHC II-(peptide-toxin) containing radiolabeled toxin.
      These findings, which provide the first evidence that cloned T cells can be
      deleted with soluble, cognate MHC II-(peptide-toxin) complexes, may have
      significant clinical relevance for antigen-specific therapy of autoimmune or
      other T cell-mediated diseases.

PMID- 7506265
TI  - Intracellular routing of GLcNAc-bearing molecules in thyrocytes: selective
      recycling through the Golgi apparatus.
AB  - Previous experiments led us to speculate that thyrocytes contain a recycling
      system for GlcNAc-bearing immature thyroglobulin molecules which prevents these
      molecules from lysosomal degradation (Miquelis, R., C. Alquier, and M. Monsigny.
      1987. J. Biol. Chem. 262:15291-15298). To confirm this hypothesis, the fate of
      GlcNAc-bearing proteins after internalization by thyrocytes was monitored and
      compared to that of fluid phase markers. Kinetic internalization studies were
      performed using 125I-GlcNAc-BSA and 131I-Man-BSA. We observed that the apparent
      intake rate as well as the amount of hydrolyzed GlcNAc-BSA are smaller than the
      corresponding values for Man-BSA. These differences were reduced by GlcNAc
      competitors (thyroglobulin and ovomucoid) or a weak base (chloroquine). Part of
      the internalized GlcNAc-BSA was released into the extracellular milieu at a
      higher rate and shorter half life (t1/2 = approximately 30 min) than the Man-BSA
      (t1/2 = approximately 8 h). Subcellular homing was first studied by cell
      fractionation after internalization using 125I-ovomucoid and 131I-BSA. During
      Percoll density gradient fractionation, endogenous thyroperoxidase was used to
      separate subsets of organelles involved in the biosynthetic exocytotic pathway.
      Incubation of the cell homogenate in the presence of DAB and H2O2 before cell
      fractionation give rise to a shift in the density of organelles containing 3.5
      times more ovomucoid than BSA. Discontinuous sucrose gradient showed that: (a)
      thyroperoxidase was colocalized with galactosyltransferase-contraining organelles
      in Golgi-rich subfractions; and (b) that at every time studied from 10 to 100
      min, the ovomucoid/BSA ratio was higher in these organelles than in other
      subfractions. Finally we also observed that: (a) ovomucoid sequestered in the
      Golgi-rich subfraction incorporated [3H]galactose; and (b) that part of
      internalized ovomucoid was localized on the Golgi stacks as well as elements of
      the trans-Golgi, as revealed by immunogold labeling on ultrathin cryosections.
      These data prove that in thyrocytes GlcNAc accessible sugar moieties on soluble
      internalized molecules are sufficient to trigger their recycling via the Golgi
      apparatus.

PMID- 7506267
TI  - Interferon-alpha induces the expression of the L-selectin homing receptor in
      human B lymphoid cells.
AB  - The L-selectin homing receptor expressed by lymphocytes mediates the initial
      attachment of these cells to high endothelial venules within peripheral lymph
      nodes. This adhesive interaction is required for the migration of B and T
      lymphocytes from the blood into peripheral lymph nodes. There is currently little
      information regarding the nature of the factors involved in the regulation of the
      synthesis and expression of L-selectin by lymphocytes. In this report, the
      immunomodulatory cytokine interferon-alpha (IFN-alpha) was shown to markedly
      upregulate the surface density of L-selectin in the established human B lymphoid
      Daudi cell line and in a subpopulation of tissue-derived human B lymphoid cells.
      Other cytokines such as IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)
      1 beta, IL-2, IL-4, IL-6, and low molecular weight B cell growth factor did not
      affect L-selectin surface expression in the model Daudi B cell line. Upregulation
      of L-selectin surface density in IFN-alpha-treated Daudi B cells correlated
      directly with an increase in L-selectin mRNA steady state levels and enhanced L
      selectin-dependent binding to a carbohydrate-based ligand, phosphomonoester core
      polysaccharide. Regulation of L-selectin mRNA by IFN-alpha had characteristics
      similar to that of classical IFN-stimulated genes including rapid kinetics of
      induction, protein-synthesis-independent induction, and sensitivity to tyrosine
      kinase inhibitors. IFN-alpha did not upregulate L-selectin mRNA levels or surface
      expression in an IFN-resistant Daudi subclone which exhibits a defect in the
      signal transduction pathway required for the transcriptional induction of IFN
      stimulated genes. These data demonstrate a fundamental role for IFN-alpha in
      regulating L-selectin synthesis and expression in human B lymphoid cells and
      suggest a mechanism whereby this cytokine regulates the regional trafficking of B
      cells to peripheral lymph nodes.

PMID- 7506266
TI  - WIF-B cells: an in vitro model for studies of hepatocyte polarity.
AB  - We have evaluated the utility of the hepatoma-derived hybrid cell line, WIF-B,
      for in vitro studies of polarized hepatocyte functions. The majority (> 70%) of
      cells in confluent culture formed closed spaces with adjacent cells. These bile
      canalicular-like spaces (BC) accumulated fluorescein, a property of bile
      canaliculi in vivo. By indirect immunofluorescence, six plasma membrane (PM)
      proteins showed polarized distributions similar to rat hepatocytes in situ. Four
      apical PM proteins were concentrated in the BC membrane of WIF-B cells.
      Microtubules radiated from the BC (apical) membrane, and actin and foci of gamma
      tubulin were concentrated in this region. The tight junction-associated protein
      ZO-1 was present in belts marking the boundary between apical and basolateral PM
      domains. We explored the functional properties of this boundary in living cells
      using fluorescent membrane lipid analogs and soluble tracers. When cells were
      incubated at 4 degrees C with a fluorescent analog of sphingomyelin, only the
      basolateral PM was labeled. In contrast, when both PM domains were labeled by de
      novo synthesis of fluorescent sphingomyelin from ceramide, fluorescent lipid
      could only be removed from the basolateral domain. These data demonstrate the
      presence of a barrier to the lateral diffusion of lipids between the PM domains.
      However, small soluble FITC-dextrans (4,400 mol wt) were able to diffuse into BC,
      while larger FITC-dextrans were restricted to various degrees depending on their
      size and incubation temperature. At 4 degrees C, the surface labeling reagent
      sNHS-LC-biotin (557 mol wt) had access to the entire PM, but streptavidin (60,000
      mol wt), which binds to biotinylated molecules, was restricted to only the
      basolateral domain. Such differential accessibility of well-characterized probes
      can be used to mark each membrane domain separately. These results show that WIF
      B cells are a suitable model to study membrane trafficking and targeting in
      hepatocytes in vitro.

PMID- 7506268
TI  - Pulsatile release of gonadotrophin releasing hormone (GnRH) is an intrinsic
      property of GT1 GnRH neuronal cell lines.
AB  - The GT1-1 gonadotrophin releasing hormone (GnRH) cell line releases GnRH in a
      pulsatile fashion. This finding demonstrates that the generation and
      synchronization of GnRH pulses is an intrinsic property of GnRH neurons. It
      appears that propagated action potentials and a Ca(2+)-coupled secretory
      mechanism are necessary for pulsatile release. The secretion of GnRH from GT1
      cells is stimulated by both norepinephrine and dopamine respectively via beta 1
      adrenergic and D1-dopaminergic receptors. These findings provide new data for the
      understanding of the complex neuroendocrine regulation of luteinizing hormone.

PMID- 7506269
TI  - Luteotrophic and luteolytic actions of ovarian peptides.
AB  - Corpora lutea of all species investigated so far, including the human, produce
      oxytocin and a variety of other regulatory peptides. The role of these peptides
      is largely unknown. The subtypes of large luteal cells are able to produce tumour
      necrosis factor (TNF) and at the end of the luteal phase TNF-producing
      macrophages invade the aged corpus luteum, indicating that this cytokine may be
      involved in the process of luteolysis. The present contribution reviews briefly
      the known functions of oxytocin and substance P in the corpus luteum and then
      elaborates the possible involvement of luteal and macrophage TNF during
      luteolysis. Oxytocin applied to intact corpus luteum stimulates the secretion of
      progesterone and oestradiol. The stimulation of progesterone secretion by
      oxytocin is due to the stimulated oestrogen production. TNF, when tested in
      vitro, inhibits both luteal cell progesterone and oestradiol production. The TNF
      mediated inhibition of aromatase activity therefore prevents the luteotrophic
      effects of a variety of peptides including oxytocin. This appears to be the
      mechanism by which TNF induces luteolysis.

PMID- 7506270
TI  - The organization of projections from the mediodorsal nucleus of the thalamus to
      orbital and medial prefrontal cortex in macaque monkeys.
AB  - The organization of interconnections between the mediodorsal nucleus of the
      thalamus (MD) and the orbital and medial prefrontal cortex and the agranular
      insular cortex in the monkey was studied by retrograde and anterograde tracing
      techniques. In addition to the magnocellular and parvicellular divisions of MD,
      three other subdivisions can be recognized on the basis of myeloarchitecture,
      cytoarchitecture, and connections. The first two of these represent a
      parcellation of the magnocellular division into a lateral, fiber-rich MD pars
      fibrosa and a medial, poorly myelinated MD pars paramediana adjacent to the
      midline. The third is a small, poorly myelinated area located at the caudomedial
      and dorsal edges of MD; it is referred to as MD pars caudodorsalis. MD pars
      fibrosa is reciprocally interconnected primarily with areas 11, 12 and 13 in the
      central and lateral part of the orbital cortex. There is a general organization
      within this projection, with the rostrocaudal axis of the cortex represented from
      dorsal to ventral in the pars fibrosa, and the mediolateral cortical axis
      represented from medial to lateral. Cells that project to area 12 also extend
      laterally into the adjacent pars parvicellularis. MD pars paramediana is more
      heavily interconnected with the caudal and medial portions of the orbital region,
      particularly the agranular insular areas and the caudal parts of areas 13 and 14.
      Cells that project to two caudal areas, 13a and Iad, do not fit with the general
      organization, in that they are located in the dorsomedial parts of the pars
      fibrosa and pars paramediana, where they overlap with cells that project to area
      14. The pars fibrosa and pars paramediana receive inputs from areas of the
      ventral forebrain such as the amygdala, piriform (olfactory) cortex, and
      entorhinal cortex, which project directly to the orbital and agranular insular
      cortex, as well as from the ventral pallidum. MD pars caudodorsalis is
      reciprocally interconnected with areas 14, 24, and 32 on the medial surface of
      the prefrontal cortex. In this part of the nucleus the dorsoventral axis of the
      medial prefrontal cortex is represented from caudal to rostral in the thalamus.
      The amygdala and other ventral forebrain structures do not send fibers into the
      pars caudodorsalis, even though some of these structures project directly to the
      medial prefrontal cortex. Ventral to MD, and separated from it by the internal
      medullary lamina, a small region was recognized that appears to be comparable to
      the anteroventral part of the submedial nucleus previously defined in the rat and
      cat.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7506271
TI  - Calcium dependence of differentiation of GABA immunoreactivity in spinal neurons.
AB  - The developmental regulation of neurotransmitter synthesis has been extensively
      studied and appears in many cases to depend on electrical activity. The central
      nervous system of the Xenopus embryo and young larva is an attractive subject for
      such studies, since action potentials first elicited from Xenopus spinal neurons
      at the time of closure of the neural tube are long in duration and calcium
      dependent. Moreover, cells exhibit spontaneous elevations of intracellular
      calcium during this early period as a consequence of calcium influx through
      voltage-dependent channels, which induces calcium release from intracellular
      stores. Since the early differentiation of Xenopus spinal neurons in dissociated
      cell culture parallels development in vivo, we have examined the maturation of
      gamma-aminobutyric acid (GABA) immunoreactivity in cultured neurons and explored
      its dependence on spontaneous calcium influx at early stages of development. We
      find that specific GABA immunoreactivity develops in spinal neurons in
      dissociated cell culture with the same time course previously defined in vivo.
      Additionally, this process requires calcium influx that occurs spontaneously
      through voltage-dependent channels. The appearance of GABA immunoreactivity is
      blocked by transcriptional inhibitors. The early appearance of GABA raises the
      possibility that it may play additional roles at early stages of development.

PMID- 7506273
TI  - Why should we use PUVA treatment in pigmented purpuric lichenoid dermatitis?

PMID- 7506272
TI  - Projections from the nucleus tractus solitarii to the spinal cord.
AB  - Projections from the nucleus tractus solitarii (NTS) to the spinal cord were
      demonstrated in the male Sprague-Dawley rat. In retrograde transport studies, a
      horseradish peroxidase conjugate or a fluorescent dye, FluoroGold, were injected
      into midcervical or upper thoracic spinal segments. Most solitariospinal neurons
      were multipolar or bipolar and located between the obex and spinomedullary
      junction. Solitariospinal neurons were concentrated in proximity to the ventral
      border of the solitary tract and extended dorsally into the intermediate division
      and ventrolaterally into the intermediate reticular zone (IRt) of the lateral
      tegmental field. This subgroup predominantly projects to midcervical spinal
      segments. A subset of small neurons was retrogradely labeled from cervical or
      thoracic spinal segments in the medial commissural nucleus and contiguous with a
      periventricular group surrounding the central canal. In anterograde transport
      studies, iontophoretic deposits of Phaseolus vulgaris leucoagglutinin were
      centered stereotaxically on sites in NTS identified by retrograde transport data.
      The lectin was incorporated by neurons of the solitary complex and transported
      bilaterally by axons that emerged from the nucleus and entered the reticular
      formation. The solitario-reticular (transtegmental) pathway irradiated diagonally
      across the IRt and extended caudally into the cervical lateral funiculus and
      spinal gray. A small periventricular-spinal pathway also descended longitudinally
      to the neuraxis. Solitariospinal neurons project to superficial lamina of the
      dorsal horn, laminae VII and X and ventral horn. The projections are
      predominantly contralateral to phrenic and intercostal motor nuclei and
      ipsilateral to the intermediolateral cell column. The solitariospinal projection
      represents the shortest route in the central nervous system, other than the local
      intraspinal reflex, through which first order visceral afferents signal
      cardiorespiratory and alimentary motor nuclei.

PMID- 7506274
TI  - Expression of the human hematopoietic progenitor cell antigen CD34 in
      dermatofibrosarcoma protuberans, other spindle cell tumors, and vascular lesions.

PMID- 7506275
TI  - Keratin and keratinization.
AB  - A flood of new knowledge and discoveries in the basic science of keratins and
      keratinization has appeared in the past several years. This review summarizes
      this recent information with a focus on the epithelial keratin polypeptides,
      keratin intermediate filaments, keratohyaline granule proteins, cell envelope
      formation and cell envelope proteins, "soft" keratinization, true disorders of
      keratinization (i.e., epidermolysis bullosa simplex and epidermolytic
      hyperkeratosis), and disease and drug effects on keratinization.

PMID- 7506276
TI  - Successful treatment of adult T-cell leukemia/lymphoma with MACOP-B, M-FEPA and
      VEPP-B combination chemotherapy.
AB  - A 45-year-old man was referred to our department in March of 1989. Physical
      examination showed erythroderma, palmo-plantar hyperkeratosis, generalized
      lymphadenopathy, hepatosplenomegaly, and leukemic manifestation. The lymphocyte
      count in the peripheral blood before treatment was 1.7 x 10(4) cells/mm3.
      Atypical lymphocytes such as flower cells and lobulated cells were seen in the
      peripheral blood. A sample excised from a lymph node showed immunoblastic,
      pleomorphic T cells by a modified classification scheme of the Working
      Formulation. A high level of serum LDH was detected (2.1 times the upper normal
      limit). Anti HTLV-1 antibody was also detected in the serum. The atypical
      lymphocytes were positive for CD3, CD4, CD5, CD7 and HLA-DR, and negative for
      CD8. Thus, the clinical, pathologic and immunologic features were those of
      typical acute-type ATL. The patient was treated with VEPA-M for three months
      starting in March of 1989. Because of poor response, the patient was then treated
      with MACOP-B, M-FEPA, and VEPP-B for about one year from June of 1989 and has
      been free of disease up to the time of writing, March of 1993.

PMID- 7506277
TI  - Aging and marrow neutrophil reserves.
AB  - OBJECTIVES: Measurement of blood neutrophil (PMN) counts after the administration
      of hydrocortisone, granulocyte colony-stimulating factor (G-CSF) and epinephrine.
      DESIGN: Prospective study, with subjects serving as their own controls before and
      after administration of hydrocortisone, G-CSF, and epinephrine. SETTING: The G
      CSF and hydrocortisone studies were conducted at the Clinical Research Center,
      University of Washington, and the epinephrine study was conducted at the Seattle
      VA Medical Center. PARTICIPANTS: Healthy volunteers of both sexes (ages 20 to 30
      years and 70 to 80 years) were recruited from the community. The subjects had no
      acute or chronic medical problems and were on no prescription medications. MAIN
      OUTCOME MEASURES: Change in the blood PMN count after administration of
      hydrocortisone (25 and 200 mg intravenously), G-CSF (30 and 300 micrograms
      subcutaneously), or epinephrine (10, 25, and 50 ng/kg/min intravenously).
      RESULTS: Baseline PMN counts were similar for all comparison groups. The peak PMN
      response (maximum count-baseline count) to hydrocortisone was significantly less
      in the older subjects (P < 0.01) at both doses. The peak PMN responses were 4588
      +/- 418/mm3 (25 mg) and 6906 +/- 1121/mm3 (200 mg) in the young and 1886 +/-
      399/mm3 (25 mg) and 2387 +/- 372/mm3 (200 mg) in the elderly subjects. The peak
      PMN response following G-CSF was not different (P > 0.05) in the two groups at
      both the dosages: 6696 +/- 736/mm3 (30 micrograms) and 9801 +/- 893/mm3 (300
      micrograms) in the young and 6340 +/- 833/mm3 (30 micrograms) and 9733 +/-
      956/mm3 (300 micrograms) in the elderly. There was no age-related change in the
      response to epinephrine. CONCLUSIONS: Aging has no effect on baseline PMN counts,
      bone marrow PMN reserves as measured with G-CSF, and blood PMN pools as measured
      with epinephrine. However the ability to mobilize these PMNs from the marrow into
      blood, as measured by the hydrocortisone response, is significantly reduced in
      the elderly.

PMID- 7506278
TI  - O, K, and H antigens predict virulence factors, carboxylesterase B pattern,
      antimicrobial resistance, and host compromise among Escherichia coli strains
      causing urosepsis.
AB  - The O:K:H serotypes of 75 Escherichia coli blood isolates from patients with
      urosepsis were compared for the presence and expression of determinants for P
      fimbriae, hemolysin, and aerobactin; antimicrobial resistance; the
      carboxylesterase B phenotype; and associated compromising host conditions. O
      groups, K types, and O:K:H serotypes previously associated with urovirulence
      accounted for 69%, 60%, and 31% of the population, respectively. Chromosomal
      determinants for P fimbriae, hemolysin, and aerobactin were present in
      combination more commonly among strains belonging to urovirulence-associated O
      groups, K types, and O:K:H serotypes. Similarly, antimicrobial resistance was
      strikingly less prevalent, the B2 carboxylesterase phenotype more common, and
      associated host compromise less common among such strains. These data demonstrate
      that the O groups, K types, and O:K:H serotypes traditionally associated with
      urovirulence are prominent among E. coli strains causing urosepsis, in which they
      are associated with presence and expression of multiple chromosomal virulence
      factor determinants, susceptibility to antimicrobial agents, the B2
      carboxylesterase phenotype, and noncompromised hosts.

PMID- 7506279
TI  - Identification of an antigenic domain on Mycobacterium leprae protein antigen
      85B, which is specifically recognized by antibodies from patients with leprosy.
AB  - Sixty-three overlapping 15-oligomer peptides covering the 30-kDa protein antigen
      85B of Mycobacterium leprae were tested by ELISA to identify epitopes recognized
      by human antibodies. Serum samples from patients with lepromatous leprosy (LL)
      reacted mainly with peptides comprising amino acid regions (AA) 206-230, 251-280,
      and 291-325. Sera of patients with active tuberculosis who responded to the
      native 30-kDa antigen did not recognize these peptides. The antibody-binding
      specificity to the defined B cell regions was evaluated in a blind study with 71
      serum samples from patients and household contacts living in Ethiopia where
      leprosy is endemic. The peptide of AA 256-280 was recognized by 88% of LL
      patients, 15% of patients with tuberculoid leprosy, and none of the contacts.
      These findings suggest that there are major linear B cell epitopes on the M.
      leprae 30-kDa protein that are recognized by lepromin-negative LL patients,
      whereas lepromin-positive patients respond preferentially to conformational
      epitopes.

PMID- 7506280
TI  - Long-term persistence of zidovudine resistance mutations in plasma isolates of
      human immunodeficiency virus type 1 of dideoxyinosine-treated patients removed
      from zidovudine therapy.
AB  - Zidovudine (3'-azido-2',3'-dideoxythymidine)-resistant isolates of human
      immunodeficiency virus type 1 (HIV-1) were previously demonstrated in zidovudine
      treated AIDS patients. The genetic linkage of multiple mutations characteristic
      of zidovudine resistance as well as dideoxyinosine resistance were demonstrated
      by examining clones of viral reverse transcriptase after polymerase chain
      reaction amplification of plasma culture DNA. The zidovudine resistance mutations
      persisted at seven time points from 4 patients for 5-22 months despite cessation
      of zidovudine therapy (and while patients underwent dideoxyinosine therapy). One
      patient's plasma virus isolate at 14 months possessed a genotype doubly resistant
      to zidovudine and dideoxyinosine. Virus recovered from four time points showed
      intermediate to high levels of zidovudine resistance. As these genotypes were
      mainly derived from plasma culture, the zidovudine-resistant virus appears to
      persist and replicate well in vivo after cessation of zidovudine therapy.

PMID- 7506281
TI  - Isolation of a Puumala-like virus from Mus musculus captured in Yugoslavia and
      its association with severe hemorrhagic fever with renal syndrome.
AB  - An outbreak of severe hemorrhagic fever with renal syndrome (HFRS) occurred in
      1988 in Pozarevac, Serbia, Yugoslavia. The disease was diagnosed in 4 children
      and 1 adult, and 1 of the children died. Rodents were captured from the same area
      and virus isolation attempted. A hantavirus, POZ-M1, was isolated from lung
      tissues of hantavirus antigen-positive Mus musculus. Serology and restriction
      enzyme digestion of polymerase chain reaction-amplified segments from this virus
      showed that it was a strain of Puumala (PUU) virus, the causative agent of
      nephropathia epidemica. While Clethrionomys glareolus is the major rodent host
      for PUU virus, these results suggest that M. musculus may also play an important
      role in harboring and transmitting PUU-like viruses. The serologic association of
      this virus with patients with severe HFRS reaffirms that PUU-like viruses may
      cause severe disease in addition to the generally mild form normally associated
      with nephropathia epidemica.

PMID- 7506282
TI  - Nitric oxide synthase and antimicrobial armature of human macrophages.

PMID- 7506283
TI  - Epitope-specific distribution of IgG subclasses against antigenic domains on
      glycoproteins of human cytomegalovirus.
AB  - The IgG subclass pattern against linear antibody binding sites on glycoproteins
      of human cytomegalovirus (HCMV) was investigated in HCMV-positive healthy blood
      donors, human immunodeficiency virus-infected persons, sera from mothers with
      primary HCMV infection during pregnancy and their children, and sequential sera
      from transplant recipients. As antigens, three immunodominant domains capable of
      inducing neutralizing antibodies during natural infection were selected on
      glycoproteins gp58/116 (gB) and gp86 (gH). Bacterial fusion proteins representing
      these regions were used as antigens in a subclass-specific ELISA. Reactivity
      against the antibody binding site on gp86 was detected in both the IgG1 and IgG3
      subclasses. In contrast, exclusively IgG1 antibodies were found against both
      linear domains on glycoprotein complex gp58/116 and also against full-length
      gp58/116 expressed in insect cells. The data demonstrate a differential
      regulation of the antibody response to envelope components of HCMV.

PMID- 7506284
TI  - Enhancement of in vivo monoclonal antibody targeting with recombinant interferon
      and cytokines.
AB  - Up to now a number of studies have been performed to determine whether the
      combined use of cytokines and monoclonal antibodies (MAbs) directed against tumor
      associated antigens (TAA) can increase the sensitivity of radioimmunoscintigraphy
      (RIS). It is well known that human natural and recombinant interferons can
      enhance the cell surface expression of HLA Class I and II antigens as well as
      some specific tumor antigens, but there is scanty and conflicting information
      about the expression and shedding of TAA. Some authors reported that alpha-IFN
      enhances the expression of a melanoma-associated antigen (MAA), recognized by
      conventional antiserum. Other authors have found no changes in the expression of
      MAA identified by MAbs. In a pilot study on patients with malignant melanoma
      Rosenblum demonstrated an increase in tumor uptake of the anti-melanoma MAb 96.5
      after IFN administration. In our study we performed immunoscintigraphy with the
      anti-melanoma MAb 225.28S in the same patient before and after IFN administration
      in different doses. We point out the difference in biodistribution in different
      organs and in blood clearance and discuss the possibility to improve the
      sensitivity of RIS.

PMID- 7506285
TI  - EIA/IRMA test for cytokeratin 19 determination.

PMID- 7506286
TI  - Islet glucan-1,4-alpha-glucosidase: differential influence on insulin secretion
      induced by glucose and isobutylmethylxanthine in mice.
AB  - In previous in-vivo studies we have presented indirect evidence for the
      involvement of islet acid glucan-1,4-alpha-glucosidase (acid amyloglucosidase), a
      lysosomal glycogen-hydrolysing enzyme, in certain insulin secretory processes. In
      the present combined in-vitro and in-vivo investigation, we studied whether
      differential changes in islet acid amyloglucosidase activity were related to the
      insulin secretory response induced by two mechanistically different
      secretagogues, glucose and isobutylmethylxanthine (IBMX). It was observed that
      addition of the selective alpha-glucosidehydrolase inhibitor emiglitate (1
      mmol/l) to isolated pancreatic islets resulted in a marked reduction of glucose
      induced insulin release. This was accompanied by a pronounced suppression of
      islet activities of acid amyloglucosidase and acid alpha-glucosidase, whereas
      other lysosomal enzyme activities, such as acid phosphatase and N-acetyl-beta-D
      glucosaminidase, were unaffected. Furthermore, islets first incubated with
      emiglitate in the presence of high (16.7 mmol/l) glucose released less insulin
      than untreated controls in response to glucose in a second incubation period in
      the absence of emiglitate. In contrast, IBMX-induced insulin release was not
      influenced by emiglitate although accompanied by a marked reduction of islet
      activities of all three alpha-glucosidehydrolases. Basal insulin secretion (1
      mmol glucose/l) was unaffected in the presence of emiglitate. In-vivo
      pretreatment of mice with highly purified fungal amyloglucosidase ('enzyme
      replacement'), a procedure known to increase islet amyloglucosidase activity,
      resulted in a greatly enhanced insulin secretory response to an i.v. glucose
      load. The increase in insulin release was accompanied by a markedly improved
      glucose tolerance curve in these animals. In contrast, enzyme pretreatment did
      not influence the insulin response or the blood glucose levels after an i.v.
      injection of IBMX. The data lend further support to our hypothesis that islet
      acid amyloglucosidase is involved in the multifactorial insulin secretory
      processes induced by glucose but not in those involving direct activation of the
      cyclic AMP system. The results also indicate separate, or at least partially
      separate, pathways for insulin release induced by glucose and IBMX.

PMID- 7506287
TI  - Interactions of nutrients, insulin-like growth factors (IGFs) and IGF-binding
      proteins in the regulation of DNA synthesis by isolated fetal rat islets of
      Langerhans.
AB  - Insulin is a major regulatory hormone for optimal tissue growth and function in
      utero. Its continued availability to the growing fetus depends on increasing
      islet cell mass. The purpose of the study was to examine the interactions between
      nutrient availability and insulin-like growth factor (IGF) release and action
      during DNA synthesis by isolated fetal rat islets of Langerhans. Specifically, we
      wished to determine (a) whether the availability of glucose or total amino acids
      altered the release of endogenous IGF-I or -II, (b) if both IGF-I and -II were
      effective mitogens for pancreatic beta-cells, (c) whether islets released IGF
      binding proteins (IGFBPs) and their possible regulation by nutrient availability
      and (d) how IGFBPs might regulate the ability of IGFs to alter islet DNA
      synthesis. Islets of Langerhans were isolated from fetal rat pancreata on day 22
      of gestation by collagenase digestion. Islets enriched in beta-cells following a
      5-day preincubation regime were maintained in various concentrations of glucose
      (1.4-16.7 mmol/l) or amino acids (x1- x3 total concentrations), with or without
      exogenous IGF-I, -II, IGFBP-1 or IGFBP-2. The release of insulin and endogenous
      IGF-I and -II were each determined by radioimmunoassay, and IGFBP release
      characterized by Western ligand blot analysis. DNA synthesis was measured by the
      incorporation of [3H]thymidine. Isolated islets demonstrated an increased release
      of insulin in response to increasing amounts of both glucose and amino acids,
      demonstrating functional viability. Both classes of nutrients also increased the
      DNA synthetic rate of islets. Islets released almost twice as much IGF-II (0.22
      +/- 0.08 nmol/l, mean +/- S.E.M., n = 4) as IGF-I (0.14 +/- 0.03 nmol/l) in
      cultures containing 8.7 mmol glucose/l and x1 amino acids. Lesser or greater
      concentrations of glucose did not alter the release of either IGF, but the
      release of IGF-II was significantly increased (0.53 +/- 0.08 nmol/l, P < 0.01) in
      the presence of x2 amino acids. Exogenous IGF-I was fivefold more active in
      stimulating DNA synthesis by islets (half maximal concentration (ED50) 1.6 +/-
      0.4 nmol/l, n = 3) than was IGF-II (ED50 8.1 +/- 0.6 nmol/l), regardless of
      glucose concentration. Isolated islets released four species of IGFBP with
      molecular sizes of approximately 19, 25, 35 and 46 kDa respectively. The 35 kDa
      form was identified by Western immunoblot as IGFBP-2. Increasing the glucose
      concentration between 1.4 mmol/l and 16.7 mmol/l caused a dose-related increase
      in the release of the 19, 25 and 35 kDa IGFBP species.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7506288
TI  - Effect of high-protein feed supplements on concentrations of growth hormone (GH),
      insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in plasma and on
      the amounts of GH and messenger RNA for GH in the pituitary glands of adult rams.
AB  - Three groups of mature rams were maintained on diets of hay, hay + 2% lupin or
      hay + 2% cowpea for 11 weeks. Serial blood samples were taken at 15-min intervals
      for 12 h for the determination of GH and IGF-I content by radioimmunoassay and
      for IGF-binding protein-3 (IGFBP-3) levels by Western blotting. The rams were
      killed after 77 days of supplementary feeding and their pituitary glands analysed
      for content of GH and GH mRNA. Mean plasma GH and baseline GH levels were
      significantly (P < 0.01) decreased in the rams fed lupin and cowpea compared with
      controls fed hay and GH pulse amplitude was significantly (P < 0.001) decreased
      in the group fed the cowpea diet. The frequency of GH pulses was not
      significantly altered by either treatment. Plasma concentrations of IGF-I were
      elevated in rams fed lupin (P < 0.001) or cowpea (P < 0.05). IGFBP-3 levels were
      not significantly (P > 0.05) altered by either treatment. There were no
      significant differences in pituitary content of GH mRNA but pituitary content of
      GH was increased in rams fed lupin (P < 0.05) and cowpea (P = 0.07). In
      conclusion, a high-protein diet decreases plasma GH levels and increases IGF-I
      without changing plasma IGFBP-3 levels in rams. Thus ongoing synthesis of GH, as
      indicated by the mRNA levels, may cause a build up of GH stores in the pituitary
      gland.

PMID- 7506289
TI  - Interleukin-1 beta induces nitric oxide production by a mouse pituitary tumour
      cell line (AtT20/D16).
AB  - To elucidate whether anterior pituitary cells express the nitric oxide (NO)
      synthase gene, we studied the synthesis of NO and the expression of NO synthase
      (NOS) mRNA by a mouse pituitary tumour cell line (AtT20/D16). Interleukin-1 beta
      (IL-1 beta) stimulated production of NO2-/NO3-(NOx) in a time-dependent manner
      and both NOx and cyclic GMP formation were stimulated in a dose-dependent manner
      by IL-1 beta. IL-1 beta-induced NOx production and intracellular cyclic GMP
      formation were similarly blocked by an NO synthase inhibitor, NG-monomethyl-L
      arginine (LNMMA), whose effect was reversed by L-arginine, but not by D-arginine.
      Dexamethasone inhibited IL-1 beta-induced NOx production in a dose-dependent
      manner. A calmodulin inhibitor (W-7) showed no effect on IL-1 beta-induced NOx
      production, whereas cycloheximide and the actinomycin D completely inhibited NOx
      production. Northern blot analysis using cDNA for mouse macrophage-inducible NOS
      as a probe revealed the expression of inducible NOS mRNA in the cells only after
      exposure to IL-1 beta. Although IL-1 beta stimulated ACTH release from tumour
      cells, LNMMA failed to affect ACTH release stimulated by IL-1 beta. These results
      demonstrate for the first time that a pituitary tumour cell line (AtT20/D16)
      possesses cytokine-inducible and Ca2+/calmodulin-independent NOS, although NO may
      not be involved in ACTH release.

PMID- 7506290
TI  - Multiple effects of neuropeptide Y, substance P and vasoactive intestinal
      polypeptide on progesterone and oxytocin release from bovine corpus luteum in
      vitro.
AB  - Recent observations indicate that the rat ovary receives not only adrenergic but
      also peptidergic innervation. In ruminants, there are few data available on the
      extent of a possible direct regulation of the peptidergic innervation of the
      ovary including the corpus luteum (CL). The direct effects of neuropeptide Y
      (NPY), substance P (SP) and vasoactive intestinal polypeptide (VIP) on the
      release of progesterone and oxytocin from midluteal phase CL (days 8-12) were
      examined in vitro. A possible direct neural influence might provide a sensitive
      short-term control. Long-term as well as short-term effects were assessed using
      both a serum-reduced luteal cell culture and a microdialysis system (MDS) of
      luteal tissue. In the long-term experiments, luteal cells were preincubated from
      the start of the culture for 48 h with NPY, SP and VIP (10 pmol/1-100 nmol/l).
      During the following 4 h the neuropeptides showed a dose-dependent stimulation of
      progesterone release, but there was no effect on oxytocin release. LH showed a
      synergistic effect with NPY, SP and VIP on progesterone release. In the short
      term experiments, the neuropeptides were added 48 h after the start of the
      culture. All three peptides were most stimulatory to LH-supported progesterone
      release 30 min after addition, and the effect decreased greatly thereafter to the
      control level from 60 to 120 min. In contrast, LH alone induced the maximal
      progesterone stimulation at 120 min. In the MDS, a 30-min perfusion with NPY, SP
      or VIP (10 nmol/l, 100 nmol/l and 1 mumol/l) induced significant acute effects on
      progesterone and oxytocin release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506291
TI  - The influence of endocrine factors on the serum concentrations of insulin-like
      growth factor-I (IGF-I) and IGF-binding proteins.
AB  - Serum insulin-like growth factor-I (IGF-I) levels in lit (isolated GH
      deficiency), dw (panhypopituitarism), hyt (hypothyroidism) and cog (congenital
      goiter) mutant mice were found to be significantly lower than in control mice. In
      addition, liver and kidney IGF-I concentrations in mutants were also found to be
      significantly reduced compared with controls. These differences in IGF-I
      concentration were not observed in pg (genetic IGF receptor or post-receptor
      defect?) mice. These results indicated that serum IGF-I production is induced by
      thyroid hormones as well as by GH. Western blot analysis of serum IGF-binding
      protein (IGFBP) fractions revealed the following differences among the five
      mutants: the triplet of IGFBP-3 (42, 45 and 49 kDa) and IGFBP-4 (24 kDa) levels
      were significantly reduced. IGFBP-2 (32 kDa) levels were also reduced in the lit,
      hyt and cog mice, although the level in serum of dw mice was found to be greatly
      elevated. No differences in serum IGFBP levels were found in the pg mouse.
      Consequently, the ratio of IGFBP-3%: IGFBP-2% (the percentage of IGFBP-3 fraction
      of total IGFBP (IGFBP-3%) divided by that of IGFBP-2 (IGFBP-2%)) was decreased in
      GH-deficient mice but increased in hypothyroid mice, suggesting that IGFBP-3 and
      IGFBP-2 production in the liver is induced by GH and thyroid hormones
      respectively.

PMID- 7506292
TI  - Proteolytic modification of insulin-like growth factor-binding proteins:
      comparison of conditioned media from human cell lines, circulating proteases and
      characterized enzymes.
AB  - Proteolytic modification of circulating insulin-like growth factor binding
      protein-3 (IGFBP-3) has been described in a number of conditions. Using Western
      ligand blotting and SDS-PAGE analysis of fragmentation patterns of 125I-labelled
      IGFBP-3 and 125-labelled IGFBP-1, we have examined conditioned media from
      cultured human cell lines for the presence of proteolytic activity and compared
      this with the action of circulating proteases and with characterized enzymes
      including cathepsin D, kallikrein, plasmin and tissue plasminogen activator. 125I
      Labelled IGFBP-3 was incubated with serum from pregnant women, patients following
      heart surgery and patients with cancer of the breast, lung or head/neck.
      Following separation of the preincubated samples by SDS-PAGE, a distinct pattern
      of degradation fragments was observed which was similar in all cases. This
      proteolytic activity was inhibited in the presence of EDTA, phenanthroline and 4(
      2-aminoethyl)-benzenesulphonylfluoride, HCl. These proteases had no detectable
      effect on IGFBP-1. Serum-free conditioned medium from a human dermal fibroblast
      cell line, a rabdomyosarcoma, a cervical, a bladder, a chorio- and two-tongue
      squamous cell carcinoma cell lines all contained proteolytic activity which
      fragmented IGFBP-3. The pattern of fragments was similar in all cell lines but
      different from that produced by the circulating proteases. Six out of nine cell
      lines produced protease(s) which degraded IGFBP-1 in addition to IGFBP-3. Whilst
      all the characterized enzymes tested also fragmented IGFBP-3 and plasmin cleaved
      IGFBP-1, none of these acted in the same way as either circulating or cell line
      derived proteolytic activity. The activity associated with the characterized
      enzymes and cell lines was inhibited in the presence of serum from normal healthy
      subjects. These results demonstrate that the serum of pregnant women, post
      operative patients and patients with cancer contain circulating proteases which
      cause fragmentation of IGFBP-3 but have little effect on IGFBP-1. Cell-derived
      proteases were shown to act on IGFBP-3 and IGFBP-1 in a number of instances but
      are not active in the presence of circulating inhibitors. These proteases may
      play an important role in regulating the availability of IGFs to normal and
      neoplastic tissues.

PMID- 7506293
TI  - The use of 16S rDNA sequence analysis to investigate the phylogeny of
      Leptospiraceae and related spirochaetes.
AB  - The 16S rDNA sequences from 15 Leptospiraceae were determined by automated PCR
      directed cycle sequencing. Nucleotide comparisons, including those from published
      sequences for Leptospira canicola Moulton and Serpulina spp., were used to
      construct phylogenetic trees. Serpulina hyodysenteriae and S. innocens were
      related to each other but were distinct from the Leptospiraceae comprising
      Leptospira parva incertae sedis (Turneria parva H), Leptonema illini and
      Leptospira spp. The pathogenic and the saprophytic leptospires were distinct and
      separated from each other. Leptospira inadai occupied an intermediate position
      between the two forms. The pathogens formed three groups. Group I was represented
      by L. interrogans sensu stricto and L. kirschneri, Group II by L. weilii, L.
      borgpetersenii and L. santarosai, and Group III comprised L. noguchii and L.
      meyeri. The saprophytic species, L. wolbachii and L. biflexa sensu stricto shared
      about 99% sequence similarity. The freshwater isolates were distinct from the
      marine isolate L. biflexa sensu lato ancona Ancona Porto.

PMID- 7506294
TI  - Structural comparison and epitope analysis of outer-membrane protein PIA from
      strains of Neisseria gonorrhoeae with differing serovar specificities.
AB  - The sequences of the por genes, encoding outer-membrane protein PI, have been
      obtained from a number of strains of Neisseria gonorrhoeae that express PIA
      molecules with differing serovar specificities. The inferred amino acid sequences
      of the mature proteins each comprise 308 residues and show considerable homology,
      with the degree of sequence variation between PIA molecules being considerably
      less than seen previously with PIB, but more evenly distributed throughout the
      molecule. The positions of sequence variation are largely confined to the regions
      predicted to form one of eight surface-exposed loops, suggesting a more
      widespread distribution of potential antigenic diversity. The deduced amino acid
      sequences were used to synthesize peptides for epitope mapping experiments. Some
      epitopes responsible for serovar specificity or recognized by bactericidal
      monoclonal antibodies could be identified on the basis of their reactivity with
      simple linear peptides, whilst others recognized conformational epitopes. By
      comparison of sequence differences with mAb reactivity it was possible to
      identify regions that appear to contribute to such determinants, including
      separated regions of the molecule which together were required for the formation
      of the conformational epitopes. All the epitopes identified lie at or close to
      the apices of the predicted surface-exposed loops 1, 3, 6, or 8, focusing
      attention on these regions as accessible targets for immune attack.

PMID- 7506295
TI  - Antigenic and immunogenic differences in lipopolysaccharides of Escherichia coli
      J5 vaccine strains of different origins.
AB  - Escherichia coli strain J5 mutants of various origins have often been used as
      vaccines for induction of cross-reactive, cross-protective antibodies directed
      against the lipopolysaccharide (LPS) core region. The antigenic composition of
      LPS from J5 strains of different origin, i.e. strains J5(U), J5(UK), J5(2877) and
      J5(a), was investigated using monoclonal antibodies (mAbs) reactive only with LPS
      of a given chemotype, i.e. one specific for the incomplete E. coli core of the Rc
      chemotype, a second mAb reactive only with the E. coli R3 complete core, and a
      third specific for the O-antigen of E. coli serovar O111. The LPS of strains
      J5(U) and J5(a) is almost exclusively composed of LPS of the Rc chemotype, LPS of
      the J5(UK) strain is composed of Rc LPS and R3 complete core, while LPS of the
      J5(2877) strain contains Rc, R3 complete core and O-antigen. Growth of the
      bacteria in medium supplemented with galactose led to increased expression of
      complete core. The immune responses to the various strains were investigated.
      Antiserum to the J5 strain expressing the largest amount of R3 core [J5(UK)] had
      much higher anti-R3 LPS antibody titres compared to antiserum to the other
      strains. mAb 53, representative of the anti-R3 response to J5 strains containing
      complete core, bound to those E. coli LPS expressing the R3 core. Thus, the R3
      LPS, present in some J5 vaccine strains is at least partially responsible for
      some of the cross-reactivities exhibited by some anti-J5 antisera.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7506296
TI  - Identification of helper T cell antigenic sites in mice from the haemagglutinin
      glycoprotein of measles virus.
AB  - The aim of this study was to define the helper T cell epitopes on the
      haemagglutinin (H) of measles virus (MV) in BALB/c (H-2d) and TO (H-2s) mice. A
      panel of 55 synthetic peptides (15-mers, overlapping by five amino acids)
      representing 92.2% of the H protein were synthesized and tested for
      immunogenicity and ability to stimulate MV-primed lymphocytes in vitro. The
      results obtained show that mouse lymphocytes respond to defined regions of the H
      protein which differ according to mouse strain. Virus-primed lymphocytes from
      BALB/c mice responded in vitro to peptides 7, 38, 39 and 44 whereas lymphocytes
      from virus-primed TO mice responded only to peptide 39. When mice of both strains
      were immunized with the peptides, a number of peptides induced proliferative
      responses, showing that the T cell repertoire for epitopes on the H protein is
      broader than that following immunization with virus. In BALB/c mice, lymphocytes
      primed to peptides 37, 39, 40, 42 and 43 responded in vitro to MV and in TO mice,
      lymphocytes primed to peptides 14, 32, 39, 40 and 49 responded to the virus. Thus
      in both strains of mice peptide 39 behaved as a dominant T cell epitope following
      immunization with virus or peptides. When the results obtained experimentally
      were compared with sequences predicted to be T cell epitopes by a number of
      algorithms, the concordance was limited.

PMID- 7506297
TI  - Binding of neutralizing monoclonal antibodies to regions of the fusion protein of
      respiratory syncytial virus expressed in Escherichia coli.
AB  - cDNA containing the entire coding sequence of the respiratory syncytial (RS)
      virus fusion (F) protein gene (574 amino acids) and two large PstI restriction
      fragments, encoding amino acids 18 to 212 and 214 to 574, were expressed in
      Escherichia coli as C-terminal chimeras with beta-galactosidase (beta-gal) in the
      pEX expression vector system. A further cDNA fragment, overlapping the PstI
      restriction site and encoding amino acids 190 to 289, was derived by PCR and
      expressed in a similar manner. Polyclonal rabbit serum raised against RS virus
      bound to all four chimeric proteins but most strongly to those containing C
      terminal sequences. Two monoclonal antibodies (MAbs), 1E3 and RS348, capable of
      neutralizing the virus and inhibiting the viral fusion function, bound to all
      chimeras except that derived from the N-terminal PstI fragment, suggesting that
      their binding sites were located between amino acids 214 and 289. Further
      analysis of binding to expressed fragments from restriction enzyme digests and
      PCR amplification demonstrated that both antibodies bound to amino acids 253 to
      289. MAb RS348 bound to 12-mer overlapping synthetic peptides containing the
      sequence 265 to 272 (PITNDQKK) but MAb 1E3 failed to bind to any 12-mer peptide
      derived from the F protein sequence. Immunization of mice with chimeric proteins
      containing the whole F protein coding sequence or amino acids 253 to 384, which
      includes the binding site of the two MAbs identified here, failed to induce
      antibodies that recognized the native RS virus F protein or could neutralize the
      virus. This suggests that either the beta-gal partner inhibits the immune
      response to the protein or that elements missing from the protein expressed in E.
      coli, perhaps conformational or added post-translation, contribute to the
      neutralizing antibody epitope.

PMID- 7506298
TI  - Conformational constraints of conserved neutralizing epitopes from a major
      antigenic area of human respiratory syncytial virus fusion glycoprotein.
AB  - To study the conformational requirements of epitopes from a conserved antigenic
      area (area II) of respiratory syncytial (RS) virus fusion (F) glycoprotein,
      peptides of increasing length containing amino acids essential for these epitopes
      were synthesized. The synthetic peptides were tested for binding to a panel of
      neutralizing monoclonal antibodies (MAbs) for this area as well as to rabbit
      hyperimmune and human convalescent antisera. Antibody binding was dependent on
      peptide length; thus, a 61-residue peptide spanning amino acids 215 to 275 of the
      F1 subunit (peptide F215-275) reacted with more antibodies than a shorter (41
      residue) peptide F235-275, and this one with more than the (21-residue) peptide
      F255-275. Most human convalescent sera contained antibodies that reacted with
      peptides F215-275 and F235-275 but failed to react with F255-275. The results of
      antibody binding could be related to the structure adopted by the peptides in
      solution, as determined by circular dichroism spectroscopy and susceptibility of
      peptides to trypsin digestion. Pretreatment of peptide F215-275 with SDS
      abolished reactivity with certain MAbs, supporting the notion that higher order
      structures were needed for antibody binding. High titre anti-peptide antisera
      were induced in rabbits inoculated with the peptides; however, these sera failed
      to react with the native F molecule. In mice, only the largest F215-275 peptide
      induced an anti-peptide response, but their sera reacted poorly with the native F
      protein and the animals were not protected against an RS virus challenge. These
      results illustrate the potential use of synthetic peptides in studies of the F
      protein physical and antigenic structures as well as the problems in designing
      synthetic RS virus vaccines.

PMID- 7506299
TI  - Characterization and primary structure of a human immunodeficiency virus type 1
      (HIV-1) neutralization domain as presented by a poliovirus type 1/HIV-1 chimera.
AB  - The poliovirus/human immunodeficiency virus (HIV) chimera S1/env/3 presents the
      sequence DRPEGIEEEGGERDRDRS, a known glycoprotein gp41 neutralizing domain
      (residues 735 to 752) of HIV IIIB in an antigenic site of the Sabin type 1 strain
      of poliovirus. Of 10 monoclonal antibodies raised against the sequence as
      presented in S1/env/3, eight were shown to neutralize HIV IIIB in vitro whereas
      all 10 neutralized S1/env/3, suggesting that the presentation of the sequence is
      comparable between HIV and the poliovirus/HIV chimera. The monoclonal antibodies
      were characterized by the selection of escape mutants from S1/env/3 and by
      Pepscan analysis. The two methods gave similar results, identifying two epitopes
      involving amino acids corresponding to residues 740 to 743, and to residues 745
      to 750 of gp41. Mutations selected in the chimera with S1/env/3-specific MAbs are
      identical or similar to changes occurring in vivo in natural isolates of HIV-1.
      This finding suggests that the epitope may be significant in the neutralization
      of HIV in vivo.

PMID- 7506300
TI  - Antisera raised against the second variable region of the external envelope
      glycoprotein of human immunodeficiency virus type 1 cross-neutralize and show an
      increased neutralization index when they act together with antisera to the V3
      neutralization epitope.
AB  - Antibodies have been raised against a synthetic peptide (IRDKIQKENALFRNL)
      containing a neutralizing epitope within the second variable region of the human
      immunodeficiency virus type 1 (HIV-1) SF2 strain external envelope glycoprotein
      (gp120) and also against equivalent peptides of the HIV-1 LAI, RF and MN
      isolates. The resulting antisera cross-react with heterologous peptides but
      binding to heterologous recombinant gp120 is more restricted. Antisera to HIV-1
      SF2, RF and MN are able to neutralize homologous virus. Some cross-neutralization
      is also observed, but a consensus peptide failed to induce neutralizing
      antibodies to any of the isolates studied. Antibodies to the V2 and V3 epitopes
      give a higher neutralization index when acting together than when the individual
      sera are used alone. Antibodies induced in natural infection bind to two sets of
      hexamers within the region encompassed by the 15-mer peptide, and the response to
      these can differ between infected individuals and within the same host over time.

PMID- 7506301
TI  - Molecular and biological characterization of a non-glycosylated isolate of St
      Louis encephalitis virus.
AB  - The glycosylation patterns of the envelope (E) glycoprotein of several naturally
      occurring strains of St Louis encephalitis (SLE) virus were investigated. SLE
      viruses were found that contained both glycosylated and non-glycosylated E
      proteins, and one isolate (Tr 9464) that lacks N-linked glycosylation sites on
      its E protein was identified. SLE virus monoclonal antibodies that define E
      protein B cell epitopes and demonstrate biological activities reacted essentially
      to the same extent with glycosylated and non-glycosylated virions. These results
      indicate that glycosylation is not essential for epitope conformation or
      recognition. However, failure to glycosylate the E protein was associated with
      possible morphogenetic differences as manifested by reduced virus yields and
      differences in specific infectivity.

PMID- 7506302
TI  - Effects of sequence elements in the potato virus X RNA 5' non-translated alpha
      beta-leader on its translation enhancing activity.
AB  - The 5' non-translated alpha beta-leader sequence of potato virus X RNA consists
      of two regions: the alpha sequence (41 nucleotides with no G) and the beta
      sequence (42 nucleotides upstream from AUG). The alpha beta-leader has been shown
      to enhance strongly the expression of adjacent genes in chimeric mRNAs. This
      phenomenon has been postulated to be due to the unpaired conformation of the 5'
      terminal 30 nucleotides and/or to the presence within the alpha region of the
      CCACC pentanucleotide complementary to the 3'-terminal conserved structure of 18S
      rRNA. Different derivatives of alpha beta-leader have been constructed for use in
      determining the contribution of separate elements of the alpha beta sequence to
      translational enhancement. It was found that deletion of the alpha sequence large
      fragment which was supposed to be unfolded did not reduce the delta alpha beta
      leader enhancement activity. Moreover, translational enhancement was greater for
      this derivative. Deletion of the beta sequence resulted in a considerable
      increase in activity of the alpha-leader showing that the beta region was
      dispensable for translation. Disruption or 'masking' of CCACC led to inactivation
      of the alpha beta-leader as a translational enhancer. Thus, we identified the
      CCACC pentanucleotide as the primary motif responsible for the translation
      enhancing ability of alpha beta-leader.

PMID- 7506303
TI  - Detection of activated platelets in urinary sediments by immunofluorescence using
      monoclonal antibody to human platelet GMP-140 in patients with IgA nephropathy.
AB  - The presence of activated platelets in the urinary sediments was studied by
      indirect immunofluorescence using monoclonal antigranular membrane protein (GMP)
      140 antibody. GMP-140 is generally expressed on the activated-platelets and 
      vascular endothelial cells. The purpose of the present study was to determine if
      the presence of activated platelets in the urinary sediments is correlated with
      glomerular injuries in patients with IgA nephropathy. Fourteen patients with IgA
      nephropathy and 11 patients with diffuse mesangial proliferative
      glomerulonephritis without glomerular IgA deposition (PGN) were examined. The
      number of activated platelets in the urinary sediments was markedly increased in
      patients in the advanced stage of IgA nephropathy. The ratio of activated
      platelets to total platelets in the urinary sediments was also increased in such
      patients. It appears that the detection of activated platelets in the urinary
      sediments is useful in determining the degree of histological changes in IgA
      nephropathy.

PMID- 7506304
TI  - Development of radioimmunoassays on microplate: application for CA-GI and CA-Br
      tumor markers.
AB  - By taking advantage of a newly available microplate counter for radioactivity and
      the organic solvent-resistant, pigmented microplates, we have successfully
      established radioimmunoassays (RIA) for both CA-GI and CA-BR on microplate for
      routine clinical use. In the process of assay development, we found that both
      pigmented PicoPlate, made of acrylonitrile, and polystyrene Microlite 2 can be
      coated with antialpha fetoprotein (AFP) and antinerve growth factor (NGF) and
      used for setting up immunoassays for AFP and nerve growth factors. There were no
      problems following a test format of either competitive binding or sandwich
      design. Microlites 2 is recommended over PicoPlate because Microlites 2 is made
      of polystyrene, which is less expensive and separable into 8-well strips or even
      single wells. Single-well separation allows for the use of regular gamma counters
      in case Topcount is unavailable. We also found that the sensitivity of these
      tests was not significantly affected even though Topcount counts the weaker beta
      emissions. Similar dose-response curves could also be generated between original
      Biomira tube assays and assays using PicoPlate or Microlite 2 coated with protein
      antigens CA-Br and CA-GI. Excellent correlations were also obtained between the
      microplate assays and the Biomira tube assays for CA-GI and CA-Br using groups of
      serum specimens from cancer patients. We recommend the development of various
      RIAs on the microplate: it requires less reagents and less sample handling by the
      technologists and it can be essentially automated.

PMID- 7506305
TI  - Detection of antibody IgG to HIV-1 in urine by sensitive enzyme immunoassay
      (immune complex transfer enzyme immunoassay) using recombinant proteins as
      antigens for diagnosis of HIV-1 infection.
AB  - For diagnosis of HIV-1 infection, attempts were made to detect anti-HIV-1 IgG in
      urine by sensitive enzyme immunoassay (immune complex transfer enzyme
      immunoassay) using recombinant reverse transcriptase (RT) and p17 as antigens.
      Anti-HIV-1 IgG in urine was reacted simultaneously with 2,4-dinitrophenyl-bovine
      serum albumin-recombinant protein conjugate and recombinant protein-enzyme
      conjugate. The enzymes used as labels were horseradish peroxidase for RT and
      Escherichia coli beta-D-galactosidase for p17. The complex formed, consisting of
      the three components, was trapped onto polystyrene balls coated with affinity
      purified (anti-2,4-dinitrophenyl group) IgG, eluted with epsilon N-2,4
      dinitrophenyl-L-lysine and transferred to polystyrene balls coated with affinity
      purified (anti-human IgG gamma-chain) IgG. Finally, bound enzyme activity was
      assayed by fluorometry. Urine samples were collected from 100 seronegative
      subjects and 70 seropositive subjects. The sensitivity and specificity were both
      100% with unconcentrated urine samples. The positivity was confirmed by
      preincubation of urine samples with excess of the antigens. The positivity and
      negativity with one of the two antigens could be confirmed with the other
      antigen. The positivity with low signals could be confirmed by concentration of
      urine samples. Detection of anti-HIV-1 IgG in urine by the immune complex
      transfer enzyme immunoassay using different antigens would make diagnosis of HIV
      1 infection possible.

PMID- 7506306
TI  - Expression of keratin mRNAs and proteins in normal salivary epithelia and
      pleomorphic adenomas.
AB  - Control of keratin (K) gene expression may be important for cell differentiation
      in complex epithelia such as salivary gland. To investigate differences in
      distribution between keratin mRNAs and their respective proteins, a combined in
      situ hybridization (ISH) and immunohistochemical study was undertaken on nine
      normal salivary glands and seven pleomorphic adenomas. ISH employed riboprobes to
      K7, K8, K14, K18, and K19. Immunohistochemistry was performed on adjacent
      sections using monoclonal antibodies (MAbs) to the same keratins. Normal luminal
      cells showed abundant hybridization with probes for K7, K8, K18, and K19. Keratin
      14 mRNA was present in basal and myoepithelial cells at a low level of
      expression. Proteins of their keratins were strongly stained. Neoplastic cells
      showed variable expression of mRNA and protein for K7, K8, K18, and K19. There
      was a high level of K14 mRNA but variable protein. The findings provide evidence
      that expression of these keratins in normal salivary epithelia is regulated
      transcriptionally and that in neoplasia this system is in considerable disarray.

PMID- 7506307
TI  - The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in
      human atherosclerosis.
AB  - The expression of PECAM, ICAM-1, VCAM-1, and E-selectin was studied in 64 samples
      of human coronary arteries taken from 15 explanted hearts obtained within 5 min
      of transplantation. Normal artery (n = 12), predominantly fibrous plaques (n =
      23), and plaques containing extracellular lipid (n = 26) and three segments
      showing recanalization channels were studied. All endothelial cells strongly and
      equally expressed PECAM; positive staining was used to check that artefactual
      denudation of the endothelial surface had not occurred. PECAM was also present in
      some lipid-filled macrophages. Normal arteries showed no VCAM-1 staining but
      focal segments of the endothelium were positive for ICAM-1 and E-selectin. ICAM-1
      was strongly and constantly expressed by the endothelium over all types of
      plaques and in macrophages. E-selectin expression was confined to endothelial
      cells and occurred on the surface in 35 per cent of fibrous and 22 per cent of
      lipid-containing plaques. VCAM-1 staining of surface endothelium occurred in 39
      per cent of fibrous and 20 per cent of lipid-containing plaques. A population of
      spindle-shaped cells of macrophage type (positive for EMB11 antigen) expressed
      VCAM-1 in lipid-containing plaques. Adventitial vessels adjacent to plaques
      showed endothelial expression of ICAM-1 and E-selectin. VCAM-1 staining of
      adventitial vessel endothelium was associated with local lymphoid aggregation. In
      conclusion, the expression of cell adhesion molecules is an important element in
      the inflammatory component of atherosclerosis and contributes to both monocyte
      and lymphocyte activation and recruitment from adventitial vessels and the
      arterial lumen.

PMID- 7506309
TI  - Acute pancreatitis mimicking myocardial infarction: potential for inadvertent use
      of thrombolytic therapy.

PMID- 7506308
TI  - The feeding of A type red blood cells in vitro and the ability of Schistosoma
      mansoni schistosomules to acquire A epitopes on their surfaces.
AB  - In vitro-raised Schistosoma mansoni schistosomules fed human A type red blood
      cells at day 7 postpenetration displayed A epitopes on their surfaces but not B
      epitopes when tested by the mixed agglutination procedure. Schistosomules treated
      with colchicine prior to exposure to red blood cells, exposed to plasma derived
      from human A type blood, or not exposed to host red blood cells did not display A
      epitopes on their surfaces. Under the conditions used in these experiments, it is
      likely that feeding of host red blood cells may be necessary for the tegument to
      become responsive to adsorption of host red blood cell epitopes.

PMID- 7506310
TI  - Advanced abdominal pregnancy complicated by bilateral ureteral obstruction. A
      case report.
AB  - A case of term abdominal pregnancy is reported. The patient was followed
      throughout pregnancy, but the diagnosis was made only at the time of laparotomy
      for elective cesarean section. The report exemplifies the ease with which the
      diagnosis of abdominal pregnancy can be overlooked and stresses the importance of
      considering this diagnosis in cases of high maternal serum alpha-fetoprotein. The
      management of the placenta is also discussed. In this case the retained placenta
      was managed successfully without intervention despite the unusual complication of
      bilateral ureteral obstruction. Additionally, the biochemical activity of the
      placenta was assessed by following the progressive decline of serum human
      chorionic gonadotropin over time.

PMID- 7506311
TI  - The inophyllums, novel inhibitors of HIV-1 reverse transcriptase isolated from
      the Malaysian tree, Calophyllum inophyllum Linn.
AB  - As part of a search for novel inhibitors of HIV-1 reverse transcriptase, the
      acetone extract of the giant African snail, Achatina fulica, was shown to be
      active. Fractionation of the extract yielded inophyllums A, B, C, and E and
      calophyllolide (1a, 2a, 3a, 3b, and 6), previously isolated from Calophyllum
      inophyllum Linn., a known source of nutrition for A. fulica. From a
      methanol/methylene chloride extract of C. inophyllum, the same natural products
      in considerably greater yield were isolated in addition to a novel enantiomer of
      soulattrolide (4), inophyllum P (2b), and two other novel compounds, inophyllums
      G-1 (7) and G-2 (8). The absolute stereochemistry of inophyllum A (1a) was
      determined to be 10(R), 11(S), 12(S) from a single-crystal X-ray analysis of its
      4-bromobenzoate derivative, and the relative stereochemistries of the other
      inophyllums isolated from C. inophyllum were established by a comparison of their
      1H NMR NOE values and coupling constants to those of inophyllum A (1a).
      Inophyllums B and P (2a and 2b) inhibited HIV reverse transcriptase with IC50
      values of 38 and 130 nM, respectively, and both were active against HIV-1 in cell
      culture (IC50 of 1.4 and 1.6 microM). Closely related inophyllums A, C, D, and E,
      including calophyllic acids, were significantly less active or totally inactive,
      indicating certain structural requirements in the chromanol ring. Altogether, 11
      compounds of the inophyllum class were isolated from C. inophyllum and are
      described together with the SAR of these novel anti-HIV compounds.

PMID- 7506312
TI  - Derivatives of 2-(dipropylamino)tetralin: effect of the C8-substituent on the
      interaction with 5-HT1A receptors.
AB  - A series of 2-(dipropylamino)tetralin derivatives in which the C8 substituent is
      varied has been prepared and evaluated pharmacologically to explore the
      importance of the C8 substituent in the interaction of 2-aminotetralin-based
      ligands with serotonin (5-HT1A) receptors. Enantiopure derivatives were prepared
      by facile palladium-catalyzed reactions of the triflates of the enantiomers of 8
      hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT, 1). The affinity of the compounds
      for the 5-HT1A receptors was evaluated by competition experiments with [3H]-8-OH
      DPAT in rat hippocampal and cortical tissue. In addition, the compounds were
      evaluated for central 5-HT and dopamine receptor stimulating activity in vivo by
      use of biochemical and behavioral assays in rats. With the exception of the
      carboxy-substituted derivative which is devoid of 5-HT1A receptor affinity, the
      compounds have moderate to high affinities (K(i) values range from 0.7 to 130 nM)
      for 5-HT1A receptors. Surprisingly, several of the derivatives do not produce any
      apparent effects in vivo although they have fairly high 5-HT1A receptor
      affinities. However, the methoxycarbonyl- and acetyl-substituted derivatives are
      potent 5-HT1A receptor agonists in vivo and exhibit in vitro affinities in the
      same range as the enantiomers of 1.

PMID- 7506313
TI  - Developmental changes in cytochrome oxidase histochemistry in the main and
      accessory olfactory bulbs of embryonic and neonatal garter snakes (Thamnophis
      sirtalis spp.).
AB  - Developmental studies examining the changes in oxidative metabolic activity are
      useful for understanding how and if the vomeronasal and olfactory systems respond
      to stimulation during embryogenesis. Garter snakes are good candidates for
      examining the potential functionality of the vomeronasal system in utero. In
      adult garter snakes, the vomeronasal system mediates many behaviors. Neonatal
      garter snakes exhibit these same behaviors, and the vomeronasal system has been
      shown to mediate feeding behavior in neonates. Using cytochrome oxidase
      histochemistry, we examined changes in the oxidative metabolic activity of main
      and accessory olfactory bulbs of embryonic and neonatal garter snakes (Thamnophis
      sirtalis sirtalis and T. s. parietalis). Cytochrome oxidase staining is greater
      in the accessory olfactory bulb than in the main olfactory bulb of embryonic
      garter snakes. However, neonates show no differences in the staining of the
      accessory and main olfactory bulbs, suggesting a change in the stimulation of the
      main olfactory bulb after birth. This is the first report of cytochrome oxidase
      histochemistry in reptiles and in the vomeronasal system of embryonic
      vertebrates.

PMID- 7506314
TI  - PSA and the detection of prostate cancer.

PMID- 7506315
TI  - [The surgical procedure in ulcerative gastroduodenal hemorrhage].
AB  - Analysis of the results of surgical treatment of 59 patients with gastroduodenal
      bleeding for 1991, including 41 with a duodenal ulcer, was carried out. When
      compared to the previous period, the lethality decreased almost 6-fold. This was
      associated with revision of the so-called active-expectant tactics. Performance
      of an emergency intervention is justified in persisting bleeding, and is stopped
      bleeding, but with a real danger of it recommencement within the nearest 3 days.

PMID- 7506316
TI  - Antigenic specificity and morphologic characteristics of Chlamydia trachomatis,
      strain SFPD, isolated from hamsters with proliferative ileitis.
AB  - Profound diarrhea associated with proliferating intestinal cells containing
      intraepithelial campylobacter-like organisms (ICLO) occurs in a variety of
      mammalian hosts, particularly swine and hamsters. Recently, intracellular
      bacteria were isolated from proliferative intestinal tissue of hamsters and
      propagated in intestine cell line 407. Oral inoculation of hamsters with cell
      culture lysates containing these organisms reproduced the disease in susceptible
      hamsters. In the present study, an intracellular bacterium from the INT 407 cell
      line was shown by a variety of techniques to be a member of the genus Chlamydia
      and has been designated Chlamydia sp. strain SFPD. McCoy cells infected with
      Chlamydia sp. strain SFPD demonstrated bright fluorescent-stained
      intracytoplasmic inclusions when examined with fluorescein-labeled species
      specific C. trachomatis monoclonal antibodies. The organism also reacted to
      fluorescein-labeled polyclonal but not monoclonal ICLO "omega" antisera.
      Ultrastructural examination of the Chlamydia sp. strain SFPD from McCoy cells
      revealed electrondense elementary bodies and a less electron-dense reticulate
      like body that was circular; both features are consistent in morphology to
      developmental forms of Chlamydia and do not conform to ICLO morphology. Molecular
      studies, 16S ribosomal sequence analysis, and sequencing of the outer membrane
      protein confirmed that the isolate is a C. trachomatis closely related to the
      mouse pneumonitis strain of C. trachomatis.

PMID- 7506317
TI  - Vasorelaxant properties of isolated human internal mammary arteries and saphenous
      veins: comparative effects of milrinone and sodium nitroprusside.
AB  - Internal mammary arteries (IMA) and saphenous veins (SV) are vessels currently
      used in human coronary artery bypass surgery. In addition to late complications,
      the vessels may develop spasm perioperatively. We studied isolated IMA and SV
      from patients undergoing coronary artery bypass graft to reproduce in vitro the
      phenomenon of vasospasm. Vascular rings were constricted with phenylephrine in a
      classic organ bath. The effects of two vasodilator agents, milrinone and sodium
      nitroprusside (SNP), on phenylephrine precontracted vessels and as a pretreatment
      to reverse or prevent the contraction, respectively, were studied. When added to
      a precontracted vessel, milrinone had the same vasorelaxant effect as SNP in
      artery rings (EC50: 7.4 x 10(-7) +/- 0.8 x 10(-7) vs. 5.9 x 10(-7) +/- 0.8 x 10(
      7) M, milrinone vs. SNP). In veins, milrinone was less effective in relaxing the
      rings than SNP (EC50: 15 x 10(-7) +/- 3 x 10(-7) vs. 1.5 x 10(-7) +/- 0.1 x 10(
      7) M, milrinone vs. SNP, p < 0.05). If milrinone or SNP was added as a
      pretreatment, using the EC50 values, the inhibitory effect of milrinone on
      phenylephrine-induced contractions was greater in arteries than in veins (71 +/-
      4 vs. 36 +/- 11% inhibition of maximum contraction to phenylephrine, artery vs.
      vein, p < 0.05). In arteries, milrinone caused a greater inhibitory effect than
      SNP (71 +/- 4 vs. 52 +/- 9% inhibition, milrinone vs. SNP, p < 0.05), but similar
      inhibition in veins (36 +/- 11 vs. 42 +/- 16%, milrinone vs. SNP).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7506318
TI  - Comparison of antiarrhythmic and electrophysiologic effects of diltiazem and its
      analogue siratiazem.
AB  - We compared the abilities of diltiazem and siratiazem to protect the heart
      against coronary artery occlusion and reperfusion-induced arrhythmias in
      anaesthetised rats and assessed their effects on cardiac action potentials (APs)
      recorded in paced sheep Purkinje fibres. Both drugs in the concentration range of
      0.5-4 mg kg-1 reduced the number of ventricular ectopic beats and the percentage
      of incidence of ventricular tachycardia (VT) that occurred during the first 7 min
      after coronary artery occlusion. The incidence of ventricular fibrillation (VF)
      on reperfusion was significantly reduced by siratiazem at a concentration of 2 mg
      kg-1 only. These antiarrhythmic effects were not accompanied by a reduction in
      mortality but were associated with a marked and sustained bradycardia and a
      decrease in mean arterial blood pressure (MAP). In sheep Purkinje fibres,
      diltiazem and siratiazem (10(-6)-10(-5) M) caused concentration-dependent
      reductions in AP duration measured at both 50 and 90% of repolarisation (APD50
      and APD90), in the maximum rate of depolarisation of phase 0 and in AP amplitude
      (APA). Resting membrane potential (RMP) was not modified by either drug. The
      antiarrhythmic effects of both diltiazem and siratiazem may be due in part to
      direct electrophysiologic effects on cardiac tissue to block sodium and calcium
      channels and in part to an antiischaemic effect associated with bradycardia and
      vasodepression.

PMID- 7506319
TI  - Inhibition by the combined Ca2+ and 5-HT2 receptor antagonist nexopamil (LU
      49938) of intracoronary thrombus formation in a canine model of arterial stenosis
      and intimal damage.
AB  - We investigated the effects of nexopamil, a combined Ca2+/5-HT2 antagonist on
      thrombus formation in vivo and on platelet aggregation in vitro. In anesthetized
      mongrel dogs, cyclic flow reductions (CFRs) in the left anterior descending
      coronary artery (LAD) were induced by implanting a constrictor after the
      endothelium was injured mechanically. The CFRs were due to intracoronary thrombus
      formation. After CFRs were recorded for 1 h, the test compounds were injected
      intravenously (i.v.) for 2 min. Measurements were made for another hour.
      Nexopamil (0.05 mg/kg) completely abolished CFRs during the first 30 min after
      application without significantly altering hemodynamics. The same effect was
      noted with 0.02 mg/kg ketanserin (5-HT2/alpha 1 antagonist). The Ca2+ antagonist
      gallopamil reduced CFRs only in the highest hemodynamically tolerable dose by
      40%. Serotonin-induced platelet aggregation in dog platelet-rich plasma (PRP) in
      vitro was most potently inhibited by ketanserin (IC50 0.55 x 10(-8) M), followed
      by nexopamil (IC50) 0.81 x 10(-7) M) and gallopamil (IC50 1.76 x 10(-6) M).
      Because serotonin is an important pathophysiologic mediator in unstable angina, 5
      HT2 receptor antagonism should be of considerable benefit by preventing platelet
      activation and aggregation. The combination with calcium-antagonistic activity
      leads to an increase in coronary blood flow (CBF) and a decrease in cardiac
      oxygen demand. Therefore, the effects noted with nexopamil should be of
      importance in treating patients with coronary artery disease.

PMID- 7506320
TI  - Forskolin-stimulated adenylyl cyclase activity is decreased but beta 2
      adrenoceptor function is unchanged in primary hypertension.
AB  - beta 2-Adrenoceptor function may be decreased in primary hypertension, resulting
      in increased peripheral resistance. To study the beta 2-adrenoceptor function, we
      used circulating mononuclear leukocytes (MNL) as a model system. Twenty untreated
      hypertensive subjects [(HT) 10 men and 10 women] and 20 age- and sex-matched
      healthy normotensive (NT) volunteers were studied. The beta 2-adrenoceptor
      density was not significantly different between HT and NT, but the dissociation
      constants for the high- and low-affinity agonist binding states, studied by
      isoprenaline competition assays, were significantly higher in HT. Stimulation of
      adenylyl cyclase with isoprenaline (10 microM, beta 2-adrenoceptor-mediated
      stimulation) was not significantly different between the two groups. Forskolin
      mediated direct stimulation of adenylyl cyclase was significantly higher in women
      than in men. For both sexes, the forskolin-induced cyclic AMP production was
      lower in the HT group, reaching statistical significance in the men. No major
      abnormalities were observed in beta 2-adrenoceptor function in mononuclear
      leukocytes. The putative relation between the decreased forskolin-mediated
      adenylyl cyclase activity and primary hypertension requires further study.

PMID- 7506321
TI  - High calcium diet, different antihypertensive agents, and cytosolic free Ca2+ in
      spontaneously hypertensive rats.
AB  - Several studies have shown that increased dietary calcium decreases blood
      pressure (BP) in spontaneously hypertensive rats (SHR), but the underlying
      mechanisms are not fully understood. We compared the effects of a high calcium
      diet and different antihypertensive agents on BP and intracellular free Ca2+
      concentration ([Ca2+]i) in lymphocytes of adult SHR. The calcium content of the
      normal chow was 1.1% and that of the high calcium chow was 2.5%. Antihypertensive
      drug treatments were performed by giving the animals trichlormethiazide (2
      mg/kg/day), atenolol (25 mg/kg/day), and quinapril (10 mg/kg/day) in drinking
      water. Untreated SHR and normotensive Wistar-Kyoto (WKY) rats served as controls.
      After 14 weeks of study systolic BP (SBP) and [Ca2+]i in blood lymphocytes,
      measured with a fluorescent indicator quin-2, were higher in untreated SHR than
      in WKY rats. Trichlormethiazide, atenolol, quinapril, and the high calcium diet
      all decreased BP in SHR, but only quinapril and calcium-rich diet concurrently
      reduced [Ca2+]i. We conclude that the reduction in [Ca2+]i during high calcium
      intake does not result from decreased BP itself. If the changes in lymphocyte
      [Ca2+]i reflect Ca2+ metabolism in other tissues as well, especially in vascular
      smooth muscle, the normalization of [Ca2+]i may be involved in the BP-lowering
      mechanisms of oral calcium loading and angiotensin-converting enzyme (ACE)
      inhibition in genetic hypertension.

PMID- 7506322
TI  - Systemic and renal hemodynamic responses to carvedilol and metoprolol in
      hypertensive renal transplant patients.
AB  - According to a randomized double-blind cross-over design, the short-term (8
      weeks, n = 12) and acute (2 h, n = 6) systemic and renal hemodynamic effects of
      carvedilol (25-50 mg o.d.) and metoprolol (100-200 mg o.d.) were compared in
      kidney allograft recipients with mild transplant dysfunction and arterial
      hypertension chronically treated with metoprolol. Cardiac output (Q) was measured
      by Doppler echography and renal blood flow (RBF) and glomerular filtration rate
      (GFR) were measured by constant infusion techniques using [123I]iodohippurate and
      [51Cr]EDTA, respectively. After 8 weeks, mean blood pressure (101 +/- 3 vs. 103
      +/- mm Hg) and RBF (318 +/- 14 vs. 316 +/- 14 ml/min) were comparable for the two
      drugs, whereas heart rate (HR), Q, and GFR (39 +/- 2 vs. 42 +/- 2 ml/min, p <
      0.05) were slightly lower and the RBF/Q ratio (6.4 +/- 0.4 vs. 5.8 +/- 0.4%, p <
      0.05) was higher with carvedilol than with metoprolol. During short-term
      treatment, a single dose of metoprolol acutely decreased HR and Q, carvedilol
      increased RBF, and both carvedilol and metoprolol enhanced the RBF/Q ratio and
      decreased renal vascular resistance (by 23 and 7%, p < 0.01 carvedilol vs.
      metoprolol). These data suggest that carvedilol has beneficial acute renal
      hemodynamic effects in hypertensive kidney allograft recipients with mild
      transplant dysfunction.

PMID- 7506323
TI  - Pharmacokinetics and platelet antiaggregating effects of beraprost, an oral
      stable prostacyclin analogue, in healthy volunteers.
AB  - Beraprost sodium (BPS) is an orally stable analogue of prostacyclin that inhibits
      adenylate-cyclase-dependent platelet aggregation and is proposed for treatment of
      chronic arterial occlusion. To determine the duration and intensity of platelet
      antiaggregation with BPS, 12 healthy, nonsmoking, male white volunteers
      participated in a double-blind, dose-escalating design with randomized placebo,
      placebo-controlled, cross-over study. After overnight fasting, single (20, 40, 60
      micrograms and placebo) and repeated [20, 40, 60 micrograms and placebo) and
      repeated [20, 40, 60 micrograms and placebo three times daily (t.i.d.) for 3
      days] oral doses of BPS were administered. Mean percentage of inhibition of ADP
      induced aggregation normalized to placebo was measured for 8 h after drug
      administration and related to plasma concentrations (Cp) of the active enantiomer
      (APS 314d). BPS 40 and 60 micrograms decreased platelet aggregation 1 h after
      single doses, and 0.5 h and 1 h after repeated doses. BPS 20 micrograms had no
      significant effect. APS 314d pharmacokinetics was linear, and its terminal half
      life (t 1/2) ranged from 0.50 +/- 0.21 to 0.91 +/- 0.27 h (mean +/- SD)
      independently of BPS dose. Antiaggregating effects were poorly related to Cp of
      APS 314d (r2 < or = 0.2). Some subjects complained of moderate postdrug
      absorption headaches (7 of 12 after single and 8 of 12 after repeated doses) and
      flushes (6 of 12 and 7 of 12, respectively). These data indicate that orally
      active prostacyclin BPS (40 or 60 micrograms) exerts its maximal antiaggregating
      effects between 0.5 and 1 h.

PMID- 7506324
TI  - Potent hemodynamic effects of bimakalim, a new potassium channel opener, in
      humans.
AB  - The cardiac hemodynamic effects of bimakalim, a new potassium channel opener,
      were evaluated in 12 normal volunteers by echocardiography (ECHO)/Doppler in a
      placebo-controlled, randomized double-blind, cross-over, dose-ranging study. A
      single oral dose (0.25-1 mg) was given at weekly intervals. Hemodynamic
      measurements were made at 0, 90, 120, and 240 min after drug intake and
      ECHO/Doppler was performed at 0 and 90 min. Reproducibility of the ECHO/Doppler
      study was assessed by comparing predose baseline values of the four different
      phases of treatment (placebo and 0.25, 0.5, and 1 mg) by analysis of variance
      (ANOVA), which showed no significant differences for left ventricular ejection
      fraction (LVEF). Doppler-derived stroke volume (SV), total peripheral resistance
      (TPR), and peak mitral early to late velocity ratio (PEV/PAV). ANOVA showed
      significant increases in LVEF (p = 0.0003) and SV (p = 0.03), however, and
      decreases in TPR (p = 0.002) and PEV/PAV (p = 0.005) after bimakalim treatment.
      Heart rate (HR) showed a dose-dependent increase, but systolic and diastolic
      blood pressure (SBP, DBP) did not change with bimakalim. Despite vasodilatory
      headaches, none of the volunteers discontinued the study. Bimakalim appears to be
      a potent vasodilating drug that may have an important role in management of
      patients with compromised LV function.

PMID- 7506325
TI  - Electrophysiologic and arrhythmogenic effects of the potassium channel agonist
      BRL 38227 in anesthetized dogs.
AB  - Although potassium channel openers have been demonstrated to induce arterial
      vasodilation and shortening of the QT interval, the complete in vivo hemodynamic
      and electrophysiologic profile of these drugs has not been fully established. We
      evaluated the effects of BRL 38227, the active enantiomer of cromakalim, on the
      electrophysiologic and hemodynamic parameters in anesthetized dogs. Four
      intravenous (i.v.) doses (0.01, 0.03, 0.1, and 0.3 mg/kg) of BRL 38227
      (lemakalim) were given to four different groups of 6 anesthetized and
      mechanically ventilated dogs. Electrophysiologic and hemodynamic parameters were
      measured with bipolar catheters positioned in the right atria and the right
      ventricle and double micromanometers placed in the left ventricle and the aorta.
      Nine dogs died of ventricular fibrillation (VF; 6 of 6 after 0.3 mg/kg, 2 of 8
      dogs after 0.1 mg/kg, and 1 of 7 dogs after 0.03 mg/kg BRL 38227). Three dogs had
      atrial tachycardia (1 had atrial flutter and 1 had atrial fibrillation after 0.03
      mg/kg, and 1 had atrial fibrillation after 0.01 mg/kg BRL 38227). BRL 38227 did
      not modify heart rate (HR), corrected sinus recovery time (CSRT), and atrial or
      atrio-ventricular (A-V) conduction times. In contrast, PR interval, Luciani
      Wenckebach cycle length (LW), HV interval, QRS duration, ventricular effective
      refractory period (VERP), QT interval, and monophasic action potential (AP) were
      significantly shortened in a dose-dependent manner. Left ventricular end
      diastolic pressure (LVEDP) was not modified, whereas LVdP/dtmax decreased
      significantly at 0.1 mg/kg BRL 38227. Finally, there was a significant dose
      dependent decrease in systolic, diastolic, and mean aortic blood pressure (SBP,
      DBP, MAP). We conclude that BRL 38227 shortens the ventricular parameters of
      conduction velocity and of repolarization and decreases BP, both in a dose
      dependent manner. All doses were arrhythmogenic, suggesting that BRL 38227 has a
      low safety margin.

PMID- 7506326
TI  - Effect of activation of ATP-dependent potassium channels with (-)-pinacidil and (
      )-3-pyridyl pinacidil on infarct size in a canine model of ischemia-reperfusion
      injury.
AB  - We tested the hypothesis that opening myocardial ATP-dependent K+ (ATP-K)
      channels by administration of (-)-pinacidil or (-)-3-pyridyl pinacidil
      intracoronarily (i.c.) either during ischemia or as pretreatment could decrease
      infarct size in a canine model of ischemia-reperfusion injury in anesthetized
      male hounds subjected to 90-min left circumflex coronary artery (LCX) occlusion
      followed by 5-h reperfusion. Drugs were administered by one of two protocols. In
      the postocclusion treatment protocol (protocol post), either vehicle or (-)-3
      pyridyl pinacidil [0.25 micrograms/kg/min (low dose) or 1 micrograms/kg/min (high
      dose)] was infused i.c. distal to the site of coronary artery occlusion, through
      LCX beginning 10 min after LCX occlusion and continuing until 10 min after the
      beginning of reperfusion. In the preocclusion treatment protocol (protocol pre),
      vehicle, low dose (-)-3-pyridyl pinacidil, or (-)-pinacidil (1 micrograms/kg/min)
      was infused i.c. distal to the site of coronary artery occlusion through the LCX
      beginning 10 min before occlusion and continuing until the end of the experiment.
      In both protocols, (-)-pinacidil and (-)-3-pyridyl pinacidil failed to
      demonstrate a decrease in infarct size from that of the vehicle-treated groups.
      In protocol post, the mean sizes of the infarcts in the vehicle, low-dose, and
      high-dose (-)-3-pyridyl pinacidil-treated groups were 26.4 +/- 5.0, 35.6 +/- 6.6,
      and 28.9 +/- 6.1% of the area at risk, respectively. In protocol pre, the mean
      sizes of the infarcts in the vehicle, (-)-pinacidil, and low dose (-)-3-pyridyl
      pinacidil-treated groups were 29.4 +/- 1.7, 27.0 +/- 3.9, and 35.6 +/- 4.1% of
      the area at risk, respectively. Neither subepicardial nor subendocardial blood
      flow in the ischemic zone, measured by radioactive microspheres, was
      significantly different among groups in either protocol. In protocol post,
      however, the endocardial/epicardial blood flow ration in the nonischemic zone was
      decreased by (-)-3-pyridyl pinacidil. In addition, the ischemic zone
      (LCX)/nonischemic left anterior descending coronary artery (LAD) zone blood flow
      ratio in the subepicardial region were decreased by (-)-3-pyridyl pinacidil.
      These observations suggest that the drug may shift blood flow away from the
      ischemic zone in general and away from the endocardium in particular. In protocol
      pre, the LCX/LAD ratio tended to decrease with both drugs, but the difference
      achieved statistical significance only with (-)-3-pyridyl pinacidil (low
      dose).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7506327
TI  - Responses to perivascular nerve stimulation of distal temporal arteries from dogs
      and monkeys.
AB  - In helical strips of dog distal superficial temporal artery denuded of
      endothelium and partially contracted with prostaglandin F2 alpha (PGF2 alpha),
      nicotine produced a moderate relaxation preceded by no contraction or a slight
      contraction. The contraction was less than that observed in proximal arterial
      strips obtained from the same dogs and was abolished by alpha-adrenoceptor
      antagonists. Relaxations under alpha-receptor blockade were greater in the distal
      than in the proximal arteries. Treatment with NG-nitro-L-arginine (L-NA), a
      nitric oxide (NO) synthase inhibitor, abolished the relaxation caused by nicotine
      and transmural electrical stimulation (5 Hz for 40 s), the response being
      reversed by L- but not by D-arginine. In monkey temporal arteries of the distal
      and proximal portions treated with alpha-antagonists, nicotine produced similar
      magnitudes of relaxation, which were abolished by treatment with the NO synthase
      inhibitor. Vasodilator nerves appear to play an important role in regulation of
      small arterial tone; noradrenergic vasoconstrictor function is less and
      vasodilator nerve function is more evident in dog distal arteries than in dog
      proximal arteries. The neurally induced relaxation in dog and monkey distal
      temporal arteries is postulated to be mediated by NO derived from nerves.

PMID- 7506328
TI  - Angiotensin II-mediated facilitation of sympathetic neurotransmission in the
      spontaneously hypertensive rat is not associated with neuronal uptake of the
      peptide.
AB  - Evidence suggests that angiotensin II (AII) can modulate neuroeffector responses
      in the vasculature of spontaneously hypertensive rats (SHR). Included in this
      modulation is an action of AII in facilitating release of neurotransmitter from
      sympathetic nerves by a mechanism involving prejunctional angiotensin receptors.
      In addition, AII may be a substrate for the carrier processes that operate within
      sympathetic nerves. Therefore, we examined the influence of AII on the responses
      to sympathetic nerve stimulation in the isolated perfused mesenteric vascular bed
      preparation and determined whether AII was incorporated into neuronal tissue in
      blood vessels. AII (10(-8) M) shifted the frequency-response curves to the left,
      and this shift was reversed with addition of the AII receptor type 1 (AT1)
      antagonist losartan (10(-6) M). AII uptake into mesenteric artery, thoracic
      aorta, kidney, and skeletal muscle was determined in tissues taken from SHR and
      normotensive Wistar-Kyoto rats (WKY). Additional tissues were taken from animals
      that had been subjected to chemical sympathectomy with 6-hydroxydopamine (6
      OHDA). Although AII accumulation was evident in all tissues examined, in no case
      was this accumulation diminished by 6-OHDA treatment. Subsequent studies using
      segments of kidney and skeletal muscle demonstrated that a large proportion of
      AII accumulation was temperature sensitive and was also sensitive to the
      metabolic inhibitor 2-4-dinitrophenol (DNP 10(-3) M). The results confirm the
      role of AII in potentiating the responses to sympathetic nerve stimulation
      through a process involving AT1 receptors, but this process is not associated
      with neuronal accumulation of the peptide.

PMID- 7506330
TI  - Contractility of the tail artery in rats treated with bezafibrate and fed
      atherogenic diet.
AB  - Bezafibrate, a potent hypolipidemic agent, was studied as potentially preventive
      in the atherosclerosis-associated vascular hyperresponsiveness to alpha
      adrenoceptors agonists in rats. Contractile responses to norepinephrine (NE) were
      determined in isolated tail arteries of rats fed an atherogenic or a standard
      diet. Atherogenic diet was biochemically confirmed to induce
      hypercholesterolemia. Used for 1 month, atherogenic diet increased pressor
      responses to NE in physiologic salt solution (PSS) and Ca(2+)-free PSS. When
      bezafibrate (100 mg/kg orally, p.o.) was administered simultaneously with
      atherogenic diet for 1 month, the effect was inhibited, but bezafibrate
      administered from day 15 of our experiment had no effect on vasoconstrictor
      responses to NE. Bezafibrate prevented changes in contractile responses of rat
      tail artery in the early stages of atherogenesis.

PMID- 7506329
TI  - Argatroban and inhibition of the vasomotor actions of thrombin.
AB  - We investigated the effects of the thrombin inhibitor, argatroban ((2R,4R)-4
      methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulfonyl)-L-arginyl]-2
      piperidinecarboxylic acid) on the endothelium-derived relaxing factor-nitric
      oxide (EDRF-NO)-dependent relaxant, and the endothelial cell-independent
      constrictor actions of thrombin. Experiments were performed in isolated rings of
      canine coronary arteries. Argatroban inhibited thrombin-induced relaxation (range
      of thrombin activity 0.003-0.3 U/ml), with an ED50 of 0.3 microM. The ED50 value
      was not different from inhibition of thrombin amidolytic cleavage of the
      chromogenic substrate N-p-tosylgly-pro-arg-p-nitroanilide acetate (TOGSPAN 0.28
      microM), but inhibition was highly selective. Argatroban did not block EDRF-NO
      dependent relaxations to trypsin (0.003-0.3 U/ml; Emax -88.7 + 2.0% without vs. 
      88.1 +/- 2.7% with argatroban), acetylcholine (ACh 1 nM to 1 microM; Emax -90.5
      +/- 4.7% and -88.6 +/- 3.1%, with and without argatroban, respectively), or the
      calcium ionophore A23187 (1 nM to 1 microM; Emax -98.5 +/- 1.2 vs. -99.4 +/-
      0.6%). The inhibitory effects of argatroban on thrombin-induced constriction were
      then compared with those of the irreversible thrombin inhibitor D-phenylalanyl-L
      prolyl L-arginine chloromethyl ketone (PPACK). The highest concentration of
      argatroban (10 microM) inhibited the vasoconstrictor effects of thrombin but did
      not completely block the effects (Emax 21.4 +/- 8.1% of KCl constriction without
      argatroban and Emax 14.0 +/- 5.2% of KCl-induced constriction with argatroban).
      In contrast, both a 10- and a 100-fold lower concentration of PPACK (0.1-1
      microM) prevented the thrombin-induced increase in tension. Thrombin-induced
      constriction therefore appeared to disclose mechanistic differences between the
      two thrombin inhibitors. Thrombin vasomotor actions were inhibited by argatroban,
      however, and this may contribute significantly to the therapeutic effect of
      argatroban.

PMID- 7506331
TI  - Vascular selectivity of seven prototype calcium antagonists: a study at the
      single cell level.
AB  - Vascular selective calcium antagonists (CAs) show an improved tolerance and a
      reduced incidence of adverse cardiac effects, especially in treatment of
      hypertension. The effects of seven well-known CAs on contractions of single
      isolated rat myocytes were studied and compared with their effects on stimulated
      45Ca2+ uptake of rat aortic smooth muscle cells (A7r5 cell line). In the latter
      test system, the order of potency to inhibit 45Ca2+ uptake was as follows (pIC25,
      -logM): isradipine (9.2), felodipine (8.7), nifedipine (8.5), nisoldipine (8.5),
      nicardipine (8.1), verapamil (6.7), and diltiazem (6.5). The potencies for
      inhibition of ventricular myocyte contraction at 0.5 Hz were (pIC25): isradipine
      (6.9), nisoldipine (6.7), felodipine (6.6), nicardipine (6.5), nifedipine (6.5),
      verapamil (5.3), and diltiazem (4.8). Thus, the order of vascular selectivity
      (i.e., the ratios of IC25 cardiocytes/IC25 A7r5 cells) was: isradipine (184),
      felodipine (128), nifedipine (107), nisoldipine (63), diltiazem (48), nicardipine
      (43), and verapamil (23). When ventricular cells were stimulated at 1 Hz, the
      order of selectivity was changed: Diltiazem was the least selective. Verapamil,
      diltiazem, and felodipine showed a highly frequency-dependent negative inotropic
      effect, whereas the effects of the other dihydropyridines were less affected by
      the frequency of stimulation. CAs show different degrees of vascular selectivity
      and different frequency-dependent profiles, and vascular selectivities are also
      dependent on experimental conditions. Selectivity is thus not necessarily related
      to chemical classes of drugs (e.g., dihydropyridines) or to different binding
      sites at the channel protein but could instead be due to varying dissociation
      rates from the respective binding sites at the channel in its different voltage
      dependent states.

PMID- 7506332
TI  - Recent studies on the characterization of loop diuretics.
AB  - This article provides a survey of transport mechanisms in the loop of Henle and
      of secondary effects on electrolyte excretion of loop diuretics. Results are
      presented of experiments that define ion transport in the thick ascending limb.
      New data on ion channels and transport regulation in this tubule segment are
      summarized. In addition, the mechanisms underlying enhanced sodium chloride and
      water transport after diuretics in tubule segments that are located downstream of
      the loop of Henle are surveyed. Finally, the effects of K depletion and chronic
      metabolic acidosis on diuretic potency of torasemide as well as possible
      antialdosterone effects of torasemide are evaluated.

PMID- 7506333
TI  - Renal excretory profiles of loop diuretics: consequences for therapeutic
      application.
AB  - In healthy subjects, 24-h natriuresis, kaliuresis, calciuresis, and magnesiuresis
      increase in response to the first oral dose of a standard (diuretic) formulation
      of a loop diuretic, such as furosemide 40 mg. However, low-dose formulations of
      loop diuretics, such as torasemide 2.5 mg, do not elevate 24-h natriuresis after
      the first dose is administered to normal individuals who are in steady-state
      habitual sodium balance; these formulations of loop diuretics are consequently
      labeled as nondiuretic formulations (of diuretic substances). Nondiuretic
      formulations of loop diuretics do not increase the 24-h urinary outputs of
      sodium, potassium, calcium, or magnesium after the first dose or in the course of
      repeated once-daily administration to healthy subjects. The 24-h natriuretic
      response to the first dose of standard (diuretic) formulations of loop diuretics
      wanes during repeated once-daily administration to healthy individuals, whereas
      the kaliuretic response becomes slightly attenuated, and calciuresis and
      magnesiuresis bear little change. Once-daily treatment with any formulation of a
      loop diuretic may result in an increase in plasma urate concentration.
      Nondiuretic formulations of loop diuretics, which are efficacious as once-daily
      monopharmacotherapy for high blood pressure, should be tried before standard
      (diuretic) formulations of diuretics are used in the treatment of uncomplicated
      essential hypertension. When loop diuretics are employed in the treatment of
      congestive heart failure, the minimal dose compatible with the attainment of
      clinical objectives should be used.

PMID- 7506334
TI  - Pharmacokinetics and pharmacodynamics of torasemide in health and disease.
AB  - Torasemide is a new loop diuretic that differs from others in this class in that
      only 20% of the drug is excreted unchanged in the urine with the remaining 80%
      being eliminated by hepatic metabolism. The large component of nonrenal clearance
      would predict that torasemide would have only minimal accumulation and
      prolongation of half-life in patients with renal insufficiency, and this proves
      to be the case. In contrast, in patients with liver disease, impairment of
      hepatic elimination causes accumulation of torasemide in plasma with prolongation
      of half-life. In addition, in cirrhosis, there is increased elimination of
      unchanged drug into the urine compared to healthy controls. In patients with
      renal insufficiency, response to remaining nephrons is normal as has been
      observed with other loop diuretics. In patients with cirrhosis and in those with
      congestive heart failure, response is diminished, again as has been observed with
      other loop diuretics. Interestingly, in patients with cirrhosis, the increased
      delivery of drug into the urine is sufficient to compensate for the decreased
      pharmacodynamics of response so that overall response is similar to that which
      occurs in health subjects.

PMID- 7506335
TI  - Torasemide in the treatment of arterial hypertension.
AB  - An important role for diuretics in the treatment of hypertension is assured on
      the basis of the latest randomized, prospective trials. Although thiazide
      diuretics have been the mainstay of treatment thus far, they continue to engender
      debate because of putative, undesirable side effects. Older loop diuretics, such
      as furosemide, did not establish themselves in the treatment of essential
      hypertension because of an inferior efficacy profile compared with that of
      thiazides. Torasemide is a new loop diuretic that is efficacious at low once
      daily doses in the treatment of essential hypertension. The drug compares
      favorably with hydrochlorothiazide and indapamide. Its mechanism of action may
      not be entirely based on elimination of salt and water from the body. Torasemide
      exhibits a favorable side-effect profile, particularly because it does not
      engender hypokalemia, increases in blood sugar, or serum lipid values. When the
      additional costs of potassium supplements or potassium-retaining medication are
      considered, torasemide treatment also compares favorably in terms of health-care
      economics. Torasemide represents a reasonable alternative to conventional
      diuretic management in patients with essential hypertension.

PMID- 7506336
TI  - Diuretics in heart failure: some knowns and unknowns.
AB  - There are many hemodynamic faces of heart failure, ranging from the subclinical
      to the terminal syndrome. The diuretics possess, with minor qualification, the
      pharmacotherapeutic attributes of the ideal first-line drug of choice. In heart
      failure, the loop diuretics have achieved eminence due to their improvement of
      the deranged hemodynamic profile without significant adverse pharmacologic
      effects. The new loop diuretics, including torasemide, have been shown to reduce
      the raised pulmonary vascular pressures without significant depression of the
      cardiac output in patients with chronic heart failure. This hemodynamic
      improvement has been paralleled by a significant improvement in clinical symptoms
      in the majority of patients. The undoubted and widely accepted efficacy of the
      loop diuretics in all the heart failure syndromes have presented a formidable
      ethical obstacle to their formal testing in terms of improvement in exercise
      capacity and reduction of mortality risk. There is still a paucity of information
      on their singular impact on the excited neuroendocrine reflexes in heart failure
      and their influence on the widespread metabolic disturbances occasioned by
      pumping failure of the heart. From the clinical standpoint, however, these
      deficiencies in information do nothing to reduce the importance of the loop
      diuretics in the treatment of acute and chronic heart failure.

PMID- 7506337
TI  - Loop diuretic therapy in liver cirrhosis with ascites.
AB  - Medical treatment of ascites is aimed at reverting sodium retention, that is, at
      creating a negative sodium balance to relieve ascites. Bed rest and low-sodium
      diet induce the disappearance of ascites in about 10% of patients. Loop diuretics
      and aldosterone antagonists must be administered to the patients not responding
      to the previous regimen. Available evidence indicates that aldosterone
      antagonists are the first-choice drugs, as these substances are more effective
      than furosemide. Nevertheless, loop diuretics potentiate the effects of
      aldosterone antagonists. The reduced efficacy of furosemide in these patients,
      when compared with that of spironolactone, may be related to an impairment of
      both pharmacodynamics and pharmacokinetics. In fact, most sodium not reabsorbed
      in Henle's loop, due to the action of furosemide, is subsequently taken up in the
      distal nephron because of hyperaldosteronism. A further mechanism of resistance
      may be related to an impaired excretion of furosemide into the tubular lumen. The
      use of diuretics in the treatment of ascites is associated with several side
      effects, including prerenal azotemia, hepatic encephalopathy, and electrolyte and
      acid-base disorders. A stepped-care approach, together with careful monitoring of
      patients, is the best way to reduce the incidence of these complications.
      Ethacrynic acid has been shown to be highly effective in the treatment of
      ascites, even in patients refractory to other diuretics, but its use is
      associated with a high incidence of hypokalemia and hypochloremic alkalosis.
      Bumetanide and piretanide are comparable to furosemide, in terms of both efficacy
      and side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506338
TI  - Loop diuretic therapy in acute and chronic renal failure.
AB  - The development of the powerful loop diuretics over the past 30 years has
      significantly improved the quality of life for patients with advanced chronic
      renal failure (CRF). The most recent of these drugs is torasemide. This review
      outlines its mode of action and its pharmacokinetics and pharmacodynamics in CRF.
      A personal view of the efficacy and usefulness of these drugs in CRF, CRF on
      dialysis, and in nephrotic syndrome is given. The role of loop diuretics in
      potential and/or established acute renal failure is unknown. Theoretical
      advantages are described, current knowledge reviewed, and an outline of a
      prospective study presently underway is given.

PMID- 7506339
TI  - A cryotomic method of hemisecting insect appendages for neuro-immunohistology.
AB  - A technique is described for longitudinally hemisecting small and often flexible
      appendages of arthropods, by embedding the material in frozen 30% sucrose which
      is wax-like in texture. The cleanly cut tissue is then amenable to
      immunohistochemical techniques since the problem of impenetrability of cuticle to
      antibodies is by-passed. The apparatus utilizes a simple temperature-regulated
      aluminium stage cooled by dry ice. Fixed, surcrose-infiltrated appendages are
      block-mounted on the stage, and cut with a razor blade during visual guidance
      using a dissecting microscope. A combination of hemisections and thick sections
      also can be prepared. This method has been used to demonstrate the expression of
      glionexin, a glial cell-associated glycoprotein, and ELAV, a neuronal cytoplasmic
      protein, in mechanoreceptor organs and sensilla of the cricket Acheta domesticus.

PMID- 7506340
TI  - Visualization of dendritic morphology of cortical projection neurons by
      retrograde axonal tracing.
AB  - Currently there is no reliable retrograde tracing technique for visualization of
      dendritic morphologies of projection neurons. Here we describe a simple and
      efficient method that can be used to label neurons in Golgi-like fashion. The
      approach relies on activity-dependent uptake of tracer. For this purpose we
      inject the glutamate receptor agonist N-methyl-D,L-aspartic acid (NMDA) at the
      tracer injection site to massively stimulate neurons and to thereby promote
      uptake of biocytin or biotinylated dextran amine (BDA) by axon terminals. The
      results show that co-injections of NMDA/biocytin and NMDA/BDA into the
      extrastriate lateromedial area (LM) of rat visual cortex labels large numbers of
      neurons in area 17 in Golgi-like fashion. Similarly injections of the lateral
      geniculate nucleus (LGN) lead to Golgi-like labeling of corticogeniculate neurons
      in area 17. The distribution of labeled neurons is highly topographic. In
      addition the method allows excellent preservation of ultrastructure, indicating
      that this approach is useful for determining the organization of neuronal
      circuits within the central nervous system.

PMID- 7506342
TI  - Fast axonal diffusion of 3000 molecular weight dextran amines.
AB  - The distances of anterograde and retrograde axonal movement per hour were
      examined for dextran amines of 3000, 10,000 and 40,000 molecular weights (MW)
      conjugated to different fluorochromes (Cascade blue, fluorescein,
      tetramethylrhodamine, Texas red) or to biotin. Lateral line nerves of Xenopus
      laevis tadpoles were used as an easily accessible test system. Only 10,000 and
      3000 MW dextran amines underwent significant anterograde and retrograde movement.
      Dextrans of 3000 MW progressed about twice as far (2 mm/h at 22 degrees C) than
      10,000 MW dextrans. Dextrans conjugated to different fluorochromes or to biotin
      did not show differences in their distance covered. Tracers traveled over the
      same distance in amphibians pre-treated with either 1 microM colchicine for 2-6 h
      or 10 micrograms/ml nocodazole for 5 h prior to the application to depolymerize
      microtubules needed for active transport. This suggests that diffusion is the
      major mechanism of movement for dextran amines over short distances. In the
      developing Xenopus retina, 3000 MW dextrans traveled from the optic disc as far
      away as the ora serrata within 1 h. In mouse embryos, chicken embryos and larval
      lampreys dextran amines progress within 1 h from cut peripheral nerves through
      efferent and afferent tracts. These data show that 3000 MW dextrans can be used
      in much the same way as 10,000 MW dextrans, but label neuronal profiles in a
      shorter time in a wide variety of species.

PMID- 7506341
TI  - Simultaneous local pressure microejection of excitatory amino acids and field
      potential recording with a single micropipette in the hippocampal slice.
AB  - The ability to use the same micropipette for simultaneous pressure microejection
      and field potential recording ('spot pressure electrode') is described. This
      approach allows the use of a single electrode to record both field responses to
      pressure microejection of drugs (fPR) and synaptically evoked field excitatory
      postsynaptic potentials (fEPSP). To demonstrate this, the glutamate receptor
      agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA, 100-300
      microM) and N-methyl-D-aspartate (NMDA, 1 mM) were used. Both AMPA- and NMDA
      evoked fPRs exhibited properties of postsynaptic responses. Thus, they were not
      significantly altered by tetrodotoxin (TTX, 0.5-1 microM), but were completely
      and reversibly blocked by an antagonist of AMPA/kainate receptors, 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX, 20 microM) and D-2-amino-5-phosphonopentanoic
      acid (AP5, 20 microM), respectively. The responses to micropressure-ejected AMPA
      were more stable and probably restricted to a smaller locus than responses to
      iontophoretic AMPA ejection. Additionally, the AMPA and NMDA contained in the
      pipette (up to 500 microM) did not influence the fEPSP recorded with this
      pipette. Our results suggest that this method might be a useful experimental tool
      for studying the local effects of excitatory amino acids and other compounds.

PMID- 7506343
TI  - Acute promyelocytic leukaemia, tretinoin, and granulocyte colony-stimulating
      factor.

PMID- 7506344
TI  - Contrasting evolutionary rates in the duplicate chaperonin genes of Mycobacterium
      tuberculosis and M. leprae.
AB  - A phylogenetic analysis of chaperonin (heat shock protein 60) sequences from
      prokaryotes and eukaryotes indicated that a single gene duplication event in the
      common ancestor of Mycobacterium tuberculosis, M. leprae, and Streptomyces albus
      gave rise to the duplicate chaperonin genes found in these species (designated
      HSP65 and GroEL in the mycobacterial species). Comparison of rates of synonymous
      and nonsynonymous nucleotide substitution in different gene regions suggested
      that the 5' end of the HSP65 gene was homogenized by an ancient recombination
      event between M. tuberculosis and M. leprae. In S. albus, the two duplicated
      chaperonin genes have evolved at essentially the same rate. In both M.
      tuberculosis and M. leprae, however, the GroEL gene has evolved considerably more
      rapidly at nonsynonymous nucleotide sites than has the HSP65 gene. Because this
      difference is not seen at synonymous sites, it must be due to a difference in
      selective constraint on the proteins encoded by the two genes, rather than to a
      difference in mutation rate. The difference between GroEL and HSP65 is striking
      in regions containing epitopes recognized by T cells of the vertebrate host; in
      certain cross-reactive epitopes conserved across all organisms, nonsynonymous
      sites in GroEL have evolved twice as fast as those in HSP65. It is suggested that
      these differences are correlated with differences in the way in which the
      duplicate chaperonins of M. tuberculosis and M. leprae interact with the host
      immune system.

PMID- 7506345
TI  - Phylogenetic relationships of reverse transcriptase and RNase H sequences and
      aspects of genome structure in the gypsy group of retrotransposons.
AB  - The gypsy group of long-terminal-repeat retrotransposons contains elements having
      the same order of enzyme domains in the pol gene as do retroviruses. Elements in
      the gypsy group are now known from yeast, filamentous fungi, plants, insects, and
      echinoids. Reverse transcriptase and RNase H amino acid sequences from elements
      in the gypsy group--including the recently described SURL elements, TED, Cft1,
      and Ulysses,--were aligned and analyzed by using parsimony and bootstrapping
      methods, with plant caulimoviruses and/or retroviruses as outgroups. Clades
      supported at the 95% level after bootstrapping include (1) 17.6 with 297 and (2)
      all of the SURL elements together. Other likely relationships supported at lower
      bootstrap confidence intervals include (1) SURL elements with mag, (2) 17.6 and
      297 with TED, and this collective group with 412 and gypsy, (3) Tf1 with Cft1,
      (4) IFG7 with Del, and (5) all of the retrotransposons in the gypsy group
      together, to the exclusion of Ty3. In contrast with an earlier analysis, our
      results place mag within the gypsy group rather than outside of a cluster that
      contains gypsy group retrotransposons and plant caulimoviruses. Several features
      of retrotransposon genomes provide further support for some of the aforementioned
      relationships. The union of SURL elements with mag is supported by the presence
      of two RNA binding sites in the nucleocapsid protein. Location of the tRNA primer
      binding site and the presence of a long open reading frame 3' to the pol gene
      support the 17.6-297-TED-412-gypsy cluster.

PMID- 7506346
TI  - HIV infection in babies & children.

PMID- 7506347
TI  - [Tyrosol--the autoregulatory d1 factor of the yeast Saccharomyces cerevisiae].
AB  - The autoregulatory d1 factor of the yeast, Saccharomyces cerevisiae, that induces
      the transition of vegetative cells into refractory resting forms, has been
      isolated from the cell-free culture medium as an individual crystalline compound.
      It has been shown to be 2-(4-hydroxyphenyl)ethane-1-ol which is also known as
      tyrosol. When added to the producer culture at 5-15 microM concentration, tyrosol
      stimulated the endogenous respiration of cells, but inhibited at 20-80 microM
      concentration. At 200-800 microM concentration, it induced the occurrence of
      resting forms. The action of tyrosol was not specific, for it also inhibited the
      cell respiration of the bacteria, Escherichia coli and Bacillus cereus, at 64-86
      microM concentration.

PMID- 7506348
TI  - Carbon monoxide levels during indoor sporting events--Cincinnati, 1992-1993.
AB  - Carbon monoxide (CO) produced by internal combustion engines is an indoor health
      hazard. High CO levels can occur during indoor sporting events--such as tractor
      pulls--that involve vehicles modified to achieve high horsepower. In January and
      March 1992 and January 1993, the Cincinnati Health Department evaluated CO levels
      during tractor pulls, monster-truck jumps, and a mud race event held in an indoor
      arena with a seating capacity of approximately 16,000 persons. This report
      summarizes findings from the evaluations.

PMID- 7506349
TI  - Two adjacent nuclear genes, ISF1 and NAM7/UPF1, cooperatively participate in
      mitochondrial functions in Saccharomyces cerevisiae.
AB  - We previously isolated a nuclear 5.7 kb genomic fragment carrying the NAM7/UPF1
      gene, which is able to suppress mitochondrial splicing deficiency when present in
      multiple copies. We show here that an immediately adjacent gene ISF1 (Increasing
      Suppression Factor) increases the efficiency of the NAM7/UPF1 suppressor
      activity. The ISF1 gene has been independently isolated as the MBR3 gene and
      comparison of the ISF1 predicted protein sequence with data libraries revealed a
      significant similarity with the MBR1 yeast protein. The ISF1 and NAM7 genes are
      transcribed in the same direction, and RNase mapping allowed the precise location
      of their termini within the intergenic region to be determined. The ISF1 gene is
      not essential for cell viability or respiratory growth. However as for many
      mitochondrial genes, ISF1 expression is sensitive to fermentative repression; in
      contrast expression of the NAM7 gene is unaffected by glucose. We propose that
      ISF1 could influence the NAM7/UPF1 function, possibly at the level of mRNA
      turnover, thus modulating the expression of nuclear genes involved in
      mitochondrial biogenesis.

PMID- 7506351
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Working paper no. 4. Spontaneous mutations in germ cells of the
      mouse: estimates of mutation frequencies and a molecular characterization of
      mutagenic events.

PMID- 7506352
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Working paper no. 5. Impact of the molecular spectrum of mutational
      lesions on estimates of germinal gene-mutation rates.
AB  - Review of the molecular characteristics of the variants identified at a series of
      disease loci suggests significant differences among loci in the relative
      frequency of nucleotide substitutions versus more complex events such as
      deletions. Some common features are repeatedly observed in each class of variant.
      For example, a high proportion of the nucleotide substitutions involve
      transitions of deoxycytidine and are suggested to result from deamination of
      cytosine at 5-methyl-CpG sites. Similarly, deletions of three or fewer
      nucleotides are relatively common in the non-nucleotide substitution class and
      these deletions are often associated with a seven-nucleotide core sequence. A
      significant fraction of the larger deletions and rearrangements may be associated
      with repetitive elements. Many of the deletion events do not appear to involve a
      chromosomal recombination mechanism. Mechanisms involving transcription slippage
      and chromatid exchange have been suggested as possible alternative mechanisms for
      generating deletion events. The spectrum of mutational events identified, e.g.
      nucleotide substitutions versus deletions, differs between loci and is probably a
      reflection of both the gene structure and the selective pressure to generate a
      disease phenotype. This locus specificity (at both the biological and molecular
      level) would appear to have significant potential to compromise estimates of
      increases in the gene germinal mutation rate following exposure to mutagenic
      agents.

PMID- 7506350
TI  - Cloning, sequencing and transcript analysis of the gene encoding
      formylmethanofuran: tetrahydromethanopterin formyltransferase from the
      hyperthermophilic Methanothermus fervidus.
AB  - The formylmethanofuran:tetrahydromethanopterin formyltransferase (FTR) from
      Methanothermus fervidus was partially purified and its N-terminal amino acid
      sequence determined. Using as probe a mixture of oligonucleotides derived from
      the FTR N-terminus, the corresponding gene (ftr) was cloned and sequenced. The
      ftr gene codes for 297 amino acids, corresponding to a molecular mass of 31,836
      daltons, in contrast to the 41,000 daltons estimated for the protein by sodium
      dodecylsulphate-polyacrylamide gel electrophoresis. The deduced amino acid
      sequence of the hyperthermophilic FTR from M. fervidus is 76% identical to the
      thermophilic FTR from Methanobacterium thermoautotrophicum and has a larger
      number of lysine residues. A putative ATP-binding site of the FTR is reported.
      The size of the ftr mRNA was estimated as 1000 nucleotides indicating
      monocistronic transcription of the 891 bp gene. The ftr mRNA starts 27 bp
      downstream of the centre of a putative archaeal box A motif and terminates at an
      oligo-dT stretch. In vitro transcription of the ftr gene, utilizing a
      transcription system developed for the distantly related Sulfolobus shibatae, is
      discussed with respect to the functional conservation of the basal transcription
      apparatus of Archaea.

PMID- 7506353
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Working paper no. 1. Spontaneous mutation: some conceptual
      difficulties.

PMID- 7506354
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Working paper no. 6. Estimation of genetic risks of exposure to
      chemical mutagens: relevance of data on spontaneous mutations and of experience
      with ionizing radiation.
AB  - This paper examines the impact of advances in knowledge on the molecular biology
      of human Mendelian diseases on the estimation of genetic risks of exposure to
      ionizing radiation and to chemical mutagens. More specifically, it addresses the
      question of whether and to what extent naturally occurring Mendelian diseases can
      be used as a baseline for efforts in this area. Data on the molecular nature and
      mechanisms of origin of spontaneous mutations underlying naturally occurring
      Mendelian diseases and on radiation-induced mutations in experimental systems
      suggest that for ionizing radiation, naturally occurring Mendelian diseases may
      not constitute an entirely adequate frame of reference and that current risk
      estimates for this class of diseases are conservative; these estimates however
      provide a margin of safety in formulating radiation protection guidelines.
      Currently available data on mechanisms and specificities of action of chemical
      mutagens, molecular dosimetry, repair of chemically induced adducts in the DNA,
      adduct-mutation relationships etc., permit the tentative conclusion that
      naturally occurring Mendelian diseases may provide a better baseline for genetic
      risk estimation for chemical mutagens than for ionizing radiation. With both
      ionizing radiation and chemical mutagens, the question of which Mendelian
      diseases are potentially inducible will become answerable in the near future when
      more molecular data on human genetic diseases become available. It is therefore
      essential that risk estimators keep abreast of advances in human genetics and
      integrate these into their conceptual framework. However, induced Mendelian
      diseases (especially the dominant ones which are of more immediate concern) are
      likely to represent a very small fraction of the adverse genetic effects of
      induced mutations. More attention therefore needs to be devoted to studies on the
      heterozygous effects of induced mutations.

PMID- 7506357
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Working paper no. 3. Somatic mutant frequency, mutation rates and
      mutational spectra in the human population in vivo.

PMID- 7506355
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Working paper no. 2. Spontaneous mutations in mammalian cells.
AB  - Spontaneous or background mutation in mammals plays an important role in both
      medical and evolutionary contexts. However, establishing mutation frequencies or
      rates has not always been easy. When the field of mammalian mutagenesis was in
      its infancy, the word "variant" rather than "mutant" was often used because the
      genetic nature of the observed phenotypic alterations could not be adequately
      proven. Nowadays numerous target genes have been identified in which mutant
      frequencies can be measured, and occasionally even rates can be estimated.
      Indeed, the genetic basis for 'variants' now often comes from direct DNA
      sequencing. This review describes the most often used and best understood genetic
      markers for mutation research and examines their usefulness. In addition,
      mutational specificity is compared for several loci and the use of DNA-sequence
      data in determining the origins of spontaneous mutation is also discussed. An
      important observation is that spontaneous mutation frequencies of similarly sized
      genes can vary by more than an order of magnitude. Chromosomal location, the
      nature of the gene product and mutational specificity may offer a partial
      explanation.

PMID- 7506356
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Spontaneous mutation and its place in risk assessment for chemical
      mutagens. Report of an ICPEMC Committee.

PMID- 7506358
TI  - Monitoring of benzene-exposed workers for genotoxic effects of benzene: improved
      working-condition-related decrease in the frequencies of chromosomal aberrations
      in peripheral blood lymphocytes.
AB  - The genotoxic effects of benzene were assessed in peripheral blood lymphocytes of
      49 workers occupationally exposed to benzene (3-68.7 mg/m3 in the work
      environment) for 0-2, 2-10 and more than 10 years (10, 22 and 17 workers,
      respectively). Chromosomal aberrations, SCEs and UV-induced DNA synthesis were
      used as indicators of genotoxic effects. Most of the workers were followed up in
      1991 and 1992, while the benzene concentrations were reduced to 1-18.4 mg/m3 air.
      Considered overall, in the "exposed" groups, the frequencies of chromosomal
      aberrations were significantly higher than in controls thus providing evidence
      for the clastogenic effects of benzene. However, there seems to be no correlation
      between aberration frequencies and the duration of prior exposure to benzene. In
      1991 and 1992, when the benzene concentrations were brought down, there was a
      concomitant decrease in the frequencies of chromosomal aberrations; in 1992 the
      decrease reached one third to one half of the initial frequencies, values still
      higher than in the controls. With the other genotoxic end-points, the changes
      were small and not consistent.

PMID- 7506359
TI  - Demonstration by DNA fingerprint analysis of genomic instability in mouse BALB
      3T3 cells during cell transformation.
AB  - We employed DNA fingerprint analysis to monitor DNA rearrangements in BALB 3T3
      cells transformed spontaneously or by treatment with 3-methylcholanthrene (MCA)
      and UV-C. The effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in
      combination with MCA was also examined. Twenty-three spontaneously transformed
      cells, 28 induced transformed cells (18 by 1 microgram/ml MCA, six by 5
      micrograms/ml MCA, and four by UV-C), and 31 non-transformed subclones were
      isolated from parental BALB 3T3 A31-1-1 cells. The DNAs were digested with HinfI
      and subjected to DNA fingerprint analysis with three multi-locus minisatellite
      probes, Per-6, Core, and Ins. Per-6 was the most effective probe for detecting
      DNA rearrangements. Rearranged bands detected by the Per-6 probe were observed in
      9/31 (29%) of non-transformed subclones, 14/23 (61%) of spontaneously transformed
      cells, 16/18 (89%) of cells transformed by 1 microgram/ml of MCA, 6/6 (100%) of
      cells transformed by 5 micrograms/ml MCA, and 4/4 (100%) of UV-C-transformed
      cells. Higher numbers of DNA rearrangements (> or = 3) occurred most frequently
      in the induced transformed cells. TPA enhanced the frequency of DNA
      rearrangements in cells transformed by MCA. These data indicate that (1) genomic
      DNA in BALB 3T3 cells is unstable and susceptible to rearrangement, (2) its
      instability is elevated during cell transformation, and (3) MCA and UV-C induce
      DNA rearrangements, and TPA enhances the effect of the former, probably via the
      recombination process. DNA fingerprint analysis is valuable for monitoring
      genomic instability during cell transformation.

PMID- 7506360
TI  - A simple assay for monitoring the mutagenic effects of 5-methylcytosine
      deamination in Escherichia coli.
AB  - We have developed and tested a simple phenotypic assay which monitors C to T
      transition mutations at the second C of a CCAGG sequence in the lacZ gene of
      Escherichia coli. The assay is based on new data concerning amino acid
      requirements on either side of a crucial active site residue in beta
      galactosidase, glutamic acid 461. We show that the frequency of occurrence of the
      mutation is influenced by two genes: dcm, the cytosine methylase gene, and vsr,
      one of the genes involved in very short patch repair. The assay has been used to
      evaluate the function of vsr cloned from a potential very short patch repair
      mutant.

PMID- 7506361
TI  - Comparative analysis of sister-chromatid exchanges in plant and human
      chromosomes.
AB  - Species specificity concerning the two main SCE characteristics, namely frequency
      and localization, of "spontaneous" SCEs in plant cells (root tips of Crepis
      capillaris) and in human lymphocytes was investigated under comparable
      conditions. The FPG technique was used for detection of SCEs after bifilar
      incorporation of BrdU into DNA (TB-BB). Data of parallel experiments showed that
      the frequency of SCEs in plant cells was considerably higher than that observed
      in human lymphocytes--13.2 and 7.3 SCEs per cell respectively. The difference was
      even more pronounced when the SCE frequency was estimated on the basis of DNA
      content/cell (pg). Analysis of SCE distribution was limited to SCEs localized in
      the centromere, since contradictory results most frequently concerned this
      chromosome region. The data of the present experiments showed that the frequency
      of SCEs localized in the centromere regions of plant chromosomes was considerably
      lower than that observed in human chromosomes. Compared with the relative sizes
      of the centromere regions in the two genomes, however, these frequencies proved
      to be quite similar. In both systems the centromeres were involved in SCE, as
      could be expected for random distribution, along the length of the chromosomes.

PMID- 7506362
TI  - Mitotic catastrophe is the mechanism of lethality for mutations that confer
      mutagen sensitivity in Aspergillus nidulans.
AB  - We have examined the consequences of treatment with DNA-damaging agents of uvs
      mutants and the bimD6 mutant of Aspergillus nidulans. We first established that
      wild-type Aspergillus undergoes a cell cycle delay following treatment with the
      DNA-damaging agents methyl methanesulfonate (MMS) or ultraviolet light (UV). We
      have also determined that strains carrying the bimD6, uvsB110, uvsH77, uvsF201
      and the uvsC114 mutations, all of which cause an increased sensitivity to DNA
      damaging agents, undergo a cell-cycle delay following DNA damage. These mutations
      therefore do not represent nonfunctional checkpoints in Aspergillus. However, all
      of the mutant strains accumulated nuclear defects after a period of delay
      following mutagen treatment. The nuclear defects in the uvsB110 and bimD6 strains
      following MMS treatment were shown to be dependent on passage through mitosis
      after DNA damage, as the defects were prevented with benomyl. Checkpoint controls
      responding to DNA damage thus only temporarily halt cell-cycle progression in
      response to DNA damage. The conditional bimD6 mutation also results in a
      defective mitosis at restrictive temperatures. This mitotic defect is similar to
      that seen with MMS treatment at temperatures permissive for the mitotic defect.
      Thus the bimD gene product may perform dual roles, one in DNA repair and the
      other during the mitotic cell cycle in the absence of damage.

PMID- 7506364
TI  - Measuring DNA damage in individual cells of heterogeneous mixtures: a novel
      application of an immunological typing technique.

PMID- 7506363
TI  - A case of caffeine-mediated cancellation of mitotic delay without enhanced
      breakage in V79 cells.
AB  - Chinese hamster cells (V79 379A) were grown for 17 h in the presence of 10
      micrograms/ml bromodeoxyuridine (BrdU) to obtain cells with potential sister
      chromatid differentiation. At this time batches were irradiated (1.5 Gy, 250 kVp
      X-rays) and the medium of all flasks replaced with one containing 10
      micrograms/ml thymidine with or without 400 micrograms/ml caffeine. Metaphases
      from irradiated and unirradiated batches were sampled every hour for 7 h and FPG
      stained. All categories of chromatid-type aberrations were scored in G2 and S
      phase cells. As expected, mitotic delay in the presence of caffeine, (measured by
      a shift in the portion of the fraction of differentially stained metaphases (FDM)
      curve and a reduced fall in the mitotic index) was largely cancelled, but there
      was a negligible increase in chromatid-aberration frequency (all categories),
      only achieving significance if the consistency of the whole 7-h sampling period
      was considered. Caffeine had no effect on the frequencies of light/dark chromatid
      involvement, nor in the completeness of chromatid interchanges. We conclude that
      the enhanced breakage frequency often observed with post-irradiation caffeine
      treatment is not necessarily causally related to the cancellation of delay.

PMID- 7506366
TI  - Glycolaldehyde causes DNA-protein crosslinks: a new aspect of ethylene oxide
      genotoxicity.
AB  - After in vitro incubation of human peripheral mononuclear blood cells with
      glycolaldehyde (a putative metabolite of ethylene oxide) for 2 h at 37 degrees C,
      a dose-dependent increase in DNA crosslinks was observed in a dose range between
      1 and 10 mM using the alkaline filter elution technique. The elution rate of
      mononuclear blood cells after treatment with ionizing radiation (600 cGy) was
      reduced more than 5-fold if cells were incubated with 10 mM glycolaldehyde for 2
      h. After treatment with proteinase K DNA crosslinks were no longer detected in
      cells incubated with glycolaldehyde. Therefore the crosslinks produced by
      glycolaldehyde could clearly be identified as DNA-protein crosslinks.
      Additionally glycolaldehyde induced DNA single-strand breaks in a dose range
      between 1 and 10 mM. The elution rate of mononuclear blood cells was increased
      about 18-fold if cells were incubated with 5 mM glycolaldehyde for 2 h using an
      elution procedure with proteinase K. In vitro incubation of mononuclear cells
      with ethylene oxide for 2 h at 37 degrees resulted in a dose-dependent increase
      in DNA single-strand breaks between 0.5 and 10 mM ethylene oxide. Moreover, a
      time-dependent increase in DNA single-strand breaks after incubation with 1.5 mM
      ethylene oxide was observed with an increased number of single-strand breaks
      already detectable after 15 min and a maximum level which was detected after 2 h
      of incubation. However, no DNA-DNA or DNA-protein crosslinks could be detected
      although a wide concentration range and many different incubation times were
      tested. Therefore DNA crosslinks, for which evidence was found in mononuclear
      blood cells of humans occupationally exposed to ethylene oxide, are possibly
      generated by glycolaldehyde, a putative intermediate in the metabolism of
      ethylene oxide to glycolic acid.

PMID- 7506367
TI  - Radiation-induced micronucleus formation in mouse bone marrow after low dose
      exposures.
AB  - The incidence of micronucleus formation was studied at 12, 24 and 36 h post
      irradiation in the polychromatic (PCE) and normochromatic (NCE) erythrocytes of
      the bone marrow of mice whole-body exposed to 0, 3, 9, 18, 36, 54 and 72 cGy of
      60Co gamma-radiation. It was observed that the frequency of micronucleated
      polychromatic erythrocytes (MPCE) increased with the increase in exposure dose at
      all the post-irradiation time periods studied. Similarly, the frequency of
      micronucleated normochromatic erythrocytes (MNCE) also increased with the
      increase in exposure dose and the increase for both MPCE and MNCE was dose
      related. The dose-response relationship was linear-quadratic for both MPCE and
      MNCE. The study of mitotic index revealed that a dose as low as 9 cGy is capable
      of reducing the mitotic index significantly at 24 h post-irradiation and the dose
      response was linear-quadratic. However, no significant decline in the mitotic
      index was observed at 12 and 36 h post-irradiation.

PMID- 7506365
TI  - Transgenic gpt+ V79 cell lines differ in their mutagenic response to clastogens.
AB  - Several gpt+ transgenic cell lines were derived from hprt V79 cells to study
      mutagenesis mechanisms in mammalian cells. The G12 cell line was previously shown
      to be hypermutable by X-rays and UV at the gpt locus compared to the endogenous
      hprt gene of the parental V79 cells (Klein and Rossman, 1990), and is now shown
      to be highly mutable by the clastogenic anti-tumor agent bleomycin sulfate. A
      second transgenic cell line G10, which has a different gpt insertion site, was
      studied in comparison with G12. Both G12 and G10 cell lines carry the stable gpt
      locus at a single integration site in the Chinese hamster genome, and neither
      spontaneously deletes the integrated gpt sequence at a high frequency. Although
      spontaneous mutation to 6-thioguanine resistance in G10 cells is 3-4 times higher
      than in G12 cells, the cell lines differ to a much greater extent when mutated by
      clastogens. In comparison to G12 cells, the gpt locus in G10 cells is up to 13
      times more sensitive to bleomycin mutagenesis and 5 times more responsive to X
      ray mutagenesis. In contrast, there is much less difference in UV-induced
      mutagenesis and no differences in mutagenesis induced by alkylating agents such
      as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The dose-dependent decrease in
      survival of the transgenic cells is the same for all mutagens tested, and does
      not differ from that of V79 cells. Neither transgenic cell line is generally
      hypermutable, since mutagenesis at an endogenous gene, Na+K+/ATPase, is similar
      to that of the parental V79 cell line. Although both cell lines can be induced to
      delete the transgene following clastogen exposure, deletions are not the only
      recovered mutations, and the cell lines can also be used to study mutations
      within the PCR recoverable gpt gene. The utility of these transgenic cells to
      investigate genome position effects related to mammalian mutagenesis mechanisms
      is discussed.

PMID- 7506368
TI  - The propensity for gene amplification: a comparison of protocols, cell lines, and
      selection agents.
AB  - We have studied cell lines of rodent and human origin for their propensity to
      become resistant to antifolates (methotrexate, trimetrexate), phosphonacetyl-L
      aspartate (PALA), and colcemid, resistances associated with amplification of the
      DHFR, CAD, and MDR1 genes, respectively. We have employed two different methods:
      (1) a shallow step-wise selection protocol, where time to attain specified
      resistance is the quantitative measure, (2) the frequency of resistant colonies
      at specified drug concentrations. Although there are advantages and disadvantages
      to both methods, the two methods gave the same relative ranking of cell lines.
      Striking differences in the propensity for gene amplification (resistance) were
      found: human cell lines were less prone to amplify genes than Chinese hamster
      ovary (CHO) cells. This ranking was similar with all of the agents employed.
      Additionally, we observed that whereas PALA resistance in CHO cells is associated
      with amplification of the CAD gene, PALA resistance in the two human cell lines
      studied (HeLaS3 and VA13) was not associated with amplification and/or
      overexpression of the CAD gene, and thus this resistance to PALA occurs by an
      unknown mechanism.

PMID- 7506369
TI  - Correlations between chemical reactivity and mutagenic activity against S.
      typhimurium TA100 for alpha-dicarbonyl compounds as a proof of the mutagenic
      mechanism.
AB  - The mutagenic activities in the Ames test against S. typhimurium TA100 for a
      series of alpha-dicarbonyl compounds are examined together with the formation
      constants of the adducts formed between such compounds and guanine and guanosine.
      Correlations between the equilibrium constants, the apparent reaction enthalpies,
      and the mutagenic activity are presented. These correlations imply that the
      mutagenic activity is related to the chemical reactivity of the dicarbonyl
      compounds with the puric bases.

PMID- 7506370
TI  - Base incorporation and extension at a site-specific ethenocytosine by Escherichia
      coli DNA polymerase I Klenow fragment.
AB  - Ethenocytosine (epsilon C) is a highly mutagenic exocyclic DNA lesion induced by
      carcinogens vinyl chloride and urethane. We have examined base incorporation and
      extension at a site-specific epsilon C residue by a quantitative gel
      electrophoretic assay using an exonuclease-deficient version of Escherichia coli
      DNA polymerase I (Klenow fragment) as the model enzyme. The data show that the KM
      for incorporation of adenine or thymine opposite epsilon C by is about 5 orders
      of magnitude higher than that for the incorporation of guanine opposite normal
      cytosine. The KM for base extension past epsilon C:A and epsilon C:T pairs is 1-2
      orders of magnitude higher than that observed for a C:G pair. Although adenine
      misinsertion is favored over that of thymine, base extension occurs more readily
      when the base incorporated opposite epsilon C is thymine.

PMID- 7506371
TI  - The structural basis of the genotoxicity of nitroarenofurans and related
      compounds.
AB  - The CASE (Computer-Automated Structure Evaluation) methodology has been applied
      to an investigation of the basis of the genotoxicity (sfiA induction) of 79
      nitroarenofurans and related molecules examined with the E. coli PQ37
      genotoxicity assay (SOS chromotest). CASE identified 9 major activating
      structural fragments (biophores) responsible for the probability of genotoxicity
      (SAR). With respect to quantitative features, CASE identified 8 major molecular
      subunits related to the genotoxic potency (QSAR). Both the SAR as well as the
      QSAR analysis indicate that a nitro group on position 2 of the furan ring is
      important for activity provided one or more aromatic rings are attached to the
      furan ring, i.e. 2-nitrobenzofuran, 2-nitronaphthofuran, 2-nitroanthrafuran and 8
      nitropyrenofuran. Additionally, a small substituent at position 3 of the furan
      ring, i.e. the methyl group of R7371, the ethyl group of R7427 and the butyl
      group of R7429, enhance the activity of 2-nitronaphtho[2,1-b]furan (R6597),
      whereas longer aliphatic chains decrease activity. Moreover, the activity of the
      nitro group at position 2 of the furan ring was increased by substitution of a
      methoxy group at position 7 of the R6597 structure. Additionally the n
      octanol/water partition coefficient (log P) was found to be an important
      descriptor for the genotoxic potency in E. coli PQ37. Using the identified
      descriptors CASE correctly predicted the probability of genotoxicity of all of
      the genotoxicants and non-genotoxicants in the data base. The calculated
      genotoxic potency was equally good: 94% of all predicted results were within
      plus/minus one order of magnitude of the experimental result. Using CASE in the
      predictive mode, the program correctly predicted the probability of sfiA
      induction in E. coli of 95.8% of 24 "unknown" nitroarenofurans which were not
      part of the learning set (QSAR with r = 0.88-0.97).

PMID- 7506372
TI  - Elevated frequencies of hprt mutant lymphocytes in cigarette-smoking mothers and
      their newborns.
AB  - Maternal cigarette smoking during pregnancy has been associated with increased
      perinatal mortality and low birth weight. Several epidemiological studies have
      demonstrated an association between smoking during pregnancy and an elevated risk
      of hematopoietic cancer in the child, but other studies have failed to confirm
      this association. We have used an assay for somatic cell mutation to evaluate the
      in utero effects of exposure to maternal cigarette smoking. Cord blood samples
      were obtained from 10 newborns whose mothers smoked cigarettes during pregnancy
      and 10 newborns of non-smoking mothers. Blood samples were also obtained from 5
      of the smoking and 5 of the non-smoking mothers. Smoking status was confirmed in
      all samples by testing the blood plasma for cotinine. The frequency of
      lymphocytes containing mutations at the hypoxanthine phosphoribosyltransferase
      (hprt) locus was determined with an autoradiographic assay using cells that had
      been cryopreserved. The mothers who were smokers had a mean frequency (+/- SE) of
      3.08 (+/- 0.55) variant (mutant) cells per 10(6) evaluatable lymphocytes. The
      frequency (Vf) in non-smokers was 1.07 (+/- 0.17) x 10(-6). The Vf of newborns of
      smokers was 2.17 (+/- 0.24) x 10(-6), and newborns of non-smokers had a Vf of
      0.77 (+/- 0.13) x 10(-6). In both mothers and newborns the difference in Vf
      between smokers and non-smokers was statistically significant (p < 0.05).
      Maternal and newborn Vfs were significantly correlated (r = 0.88; p < 0.004), and
      there was a positive association (r = 0.86; p < 0.001) between the reported
      number of cigarettes smoked per day and the Vfs. This study provides further
      evidence that maternal smoking may be hazardous to the future health of children
      exposed in utero to mutagenic agents in cigarette smoke.

PMID- 7506373
TI  - Different effect of thymidine kinase loss on TTP pools; comparison among human
      leukemia cell lines.
AB  - Thymidine kinase (TK)-deficient cells were established from six human leukemia
      cell lines to evaluate the role of TK in maintaining intracellular TTP pools. The
      residual TK activities in mutant cells were less than 3% of those of wild-type
      strains, except for a B-lymphoid cell line, Ball-1 (8.7%). In a promyelocytic
      leukemia cell line (HL-60), a splenic B cell line (WI-L2) and Ball-1, a
      mutational loss of TK resulted in a decrease of TTP pools by 80%, 33% and 54%,
      respectively. On the other hand, in the T cell lines, Molt-3, Molt-4 and CEM, TTP
      did not show any significant differences between parent and TK-deficient cells.
      TK-deficient HL-60 cells had, however, comparable levels of dATP, dGTP and dCTP
      with wild-type cells. An analysis of growth characteristics showed that the
      decrease of TTP was not due to the change of the cell cycle distribution. These
      results indicate that TK plays a different role in maintaining TTP pools among
      human leukemia cell lines.

PMID- 7506374
TI  - Series: 'Current issues in mutagenesis and carcinogenesis.' No. 41. Can a
      'relatively simple' screening procedure for the detection of chemicals with
      aneugenic potential be recommended at the moment?

PMID- 7506375
TI  - Series: 'Current issues in mutagenesis and carcinogenesis.' No. 42. Strategies
      and philosophies of genotoxicity testing: what is the question?
AB  - A number of statements concerning the uses and effectiveness of in vitro and in
      vivo genetic toxicity tests have recently been made. Certain of these statements
      are examined using genetic toxicity and carcinogenicity data available in the
      literature.

PMID- 7506376
TI  - Series: 'Current issues in mutagenesis and carcinogenesis.' No. 43. Mutations
      among the living and the undead.

PMID- 7506377
TI  - Lack of effect of acute acetaldehyde treatment on X chromosome segregation in
      Drosophila melanogaster females.
AB  - The effect of acute acetaldehyde treatments on X chromosome segregation was
      tested in germinal cells of Drosophila melanogaster females. The experiments were
      carried out using a test system where the nondisjunctional females (XXY) and only
      1/4 of the expected regular progeny are viable. 24 h old virgin females were
      exposed for 60 min to 3, 4 and 5% acetaldehyde solutions by means of soaked
      tissue paper placed at the bottom of regular culture vials. After mating the
      females were brooded daily. Two additional experiments were performed with 0-2 h
      old and 4-5 day old virgin females using a 4% acetaldehyde solution. The results
      obtained show that acetaldehyde did not affect X chromosomal segregation in
      oocytes. This lack of effect could result from the highly efficient ADH-ALDH
      dependent detoxifying mechanism operating in Drosophila melanogaster.

PMID- 7506378
TI  - Heterocyclic aromatic amine content of selected beef flavors.
AB  - Previous work has shown that meat extracts contain potent mutagenic and/or
      carcinogenic heterocyclic aromatic amines (HAAs). Because meat extracts and some
      beef flavors are produced from similar precursors and processing steps, the beef
      flavors may also contain HAAs. This study analyzed 24 commercial beef flavors and
      2 food-grade beef extracts for creatine and creatinine concentrations, mutagenic
      activity and HAA concentrations (IQ, MeIQ, MeIQx, DiMeIQx, Glu-P-1, Glu-P-2 and
      PhIP). The creatine and creatinine levels of the flavors ranged from 0 to 73 and
      from 0 to 21 mg/g (dry wt.), respectively. The mutagenic activities of the
      flavors ranged from 0 to 3200 Salmonella typhimurium TA98 revertants/g (dry wt.).
      No direct relationship was found between creatine and/or creatinine
      concentrations and mutagenic activities. However, flavors with high creatine (>
      1.5 mg/g) or creatinine (> 2 mg/g) levels exhibited higher mutagenic activities
      than did flavors with low levels of these compounds. Flavors with high mutagenic
      activities (> 1500 revertants/g) contained measurable amounts of HAAs. Three
      flavors contained MeIQx (7.2-21.2 ng/g [dry wt.]) and one contained DiMeIQx (4.2
      ng/g [dry wt.]).

PMID- 7506379
TI  - Cytogenetic effects of 2-methoxyethanol and its metabolite, methoxyacetaldehyde,
      in mammalian cells in vitro.
AB  - Glycol ethers such as 2-methoxyethanol (2-ME) are reproductive toxins. The
      genotoxicity of 2-ME, especially its metabolites: methoxyacetaldehyde (MALD) and
      methoxyacetic acid (MAA), is not adequately investigated yet. We have shown
      previously that MALD induced mutation in the bacterial gpt gene which is inserted
      in an autosome of CHO-AS52 cell line but not in the hprt gene on the X chromosome
      of CHO-K1-BH4 cell line. These data suggest that MALD induces major deletion-type
      mutation. If this prediction is correct we would expect to observe that MALD is
      an efficient inducer of chromosome aberrations in both CHO cell lines. We have
      conducted a cytogenetic study using both CHO cell lines and human lymphocytes to
      investigate this phenomenon. Our results show that human lymphocytes treated with
      10-30 mM MALD for 1 h or 0.05-0.5 mM MALD for 24 h induced significant dose
      dependent increase of sister-chromatid exchanges (SCE) (p < 0.05). It also
      induced significant dose-dependent increase (p < 0.05) of chromosome aberrations
      in human lymphocytes (10-40 mM treated for 1 h, or 0.05-2.5 mM for 24 h) and in
      both CHO cell lines (1.25-20 mM for 3 h). Treatment of these cells with the
      parent compound, 2-ME did not induce chromosome aberrations nor SCE unless very
      high doses of the chemical were used. In conclusion, these results indicate that
      MALD is clastogenic to different cell types therefore it is potentially
      carcinogenic. The genotoxic effects of 2-ME in humans will be dependent upon the
      metabolic capability of individuals to bioactivate 2-ME to MALD.

PMID- 7506380
TI  - Genotoxic activities in vivo of cobaltous chloride and other metal chlorides as
      assayed in the Drosophila wing spot test.
AB  - A series of metal chlorides were subjected to the wing spot test of Drosophila
      melanogaster. In the test, larvae trans-heterozygous for the wing-hair mutations
      mwh and flr were orally treated at the third instar stage with a test compound
      and the wings were inspected at the adult stage for spots expressing phenotypes
      of the markers. CoCl2, MnCl2, MoCl3, NiCl2 and ZnCl2 were clearly effective in
      inducing spots with one or two mutant hairs (small spots). CoCl2 was clearly
      effective in inducing spots with three or more mutant hairs (large spots) as
      well. CrCl3, FeCl2 and FeCl3 were negative under the conditions used. Based on
      estimated frequencies of small spots induced at the LD50, the genotoxic
      effectiveness of the positive metal salts were ranked in a sequence of CoCl2 >
      ZnCl2 > MoCl3 > (MnCl2, NiCl2). Since CoCl2 did not induce large spots in the
      wings of the mwh/TM3 flies with a suppressed ability of mitotic crossing-over,
      the large spots induced by this compound in the mwh/flr system were ascertained
      as mutant clones due to mitotic crossing-overs.

PMID- 7506382
TI  - 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) is a weak in vivo clastogen as
      revealed by the micronucleus assay.
AB  - The in vivo clastogenicity of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2)
      was examined in the micronucleus test using peripheral blood from three mouse
      strains (ICR, CD-1, and MS/Ae) and bone marrow from one rat strain (Sprague
      Dawley). Doses up to the maximum tolerated were tested. The chemical was given
      once, twice, thrice, or four times via either the i.p. or p.o. route. Under some
      conditions, ICR and CD-1 mice showed an increased frequency of micronucleated
      reticulocytes, but definite conclusions were difficult to draw because the
      increases were very slight. MS/Ae mice showed a markedly elevated micronucleated
      reticulocyte frequency after the double and triple ip treatments. Rats showed a
      slightly but statistically significantly increased frequency of micronucleated
      polychromatic erythrocytes after double i.p. treatments. These results indicate
      that AF-2 is a weak in vivo clastogen.

PMID- 7506381
TI  - Effect of low power microwave on the mouse genome: a direct DNA analysis.
AB  - The potential mutagenic effect of low power microwave at the DNA sequence level
      in the mouse genome was evaluated by direct DNA analysis. Animals were exposed to
      microwave at a power density of 1 mW/cm2 for 2 h/day at a frequency of 2.45 GHz
      over a period of 120, 150 and 200 days. HinfI digested DNA samples from testis
      and brain of control and exposed animals were hybridized with a synthetic oligo
      probe (OAT 36) comprising nine repeats of 5'-GACA-3'. As compared to control
      animals, band patterns in exposed animals were found to be distinctly altered in
      the range of 7-8 kb which was also substantiated by densitometric analysis.
      Though the mechanism of this rearrangement is not yet clear, the results obtained
      at the present dose are of significance. This dose, which has been set as the
      safe limit for general public exposure by the Non-Ionizing Radiation Committee of
      the International Radiation Protection Association, may imply a need for
      (re)evaluation of the mutagenic potential of microwaves at the prescribed safe
      limit for the personnel and people who are being exposed.

PMID- 7506383
TI  - Micronuclei induced by selenium, mercury, methylmercury and their mixtures in
      binucleated blocked fish erythrocyte cells.
AB  - The genotoxic effects of low concentrations of Se(IV), Hg2+, and CH3HgCl added
      separately or together (Se(IV)/CH3HgCI) were studied by determining the induction
      of micronuclei in the binucleated erythrocytes of Prussian carp. The frequencies
      of micronuclei were elevated in a dose-dependent manner in all treatments when
      compared to the relevant controls. Addition of Se(IV) reduced the frequencies of
      micronuclei in treatments with both forms of mercury. This novel approach to
      genotoxicity testing using binucleated cytokinesis-blocked erythrocytes in fish
      appears to be worth further study as a method for monitoring the genotoxicity of
      waterborne pollutants.

PMID- 7506384
TI  - Cytogenetic monitoring of fishermen with environmental mercury exposure.
AB  - Due to high mercury levels in many Mediterranean aquatic organisms, people who
      live in this area and consume large amounts of seafood are exposed to a
      toxicological hazard. A group of 51 fishermen exposed to mercury through eating
      contaminated seafood from the northern Tyrrhenian Sea underwent cytogenetic
      monitoring. This work is part of a research project consisting of the evaluation
      of micronuclei (MN), chromosomal aberrations (CA) and sister-chromatid exchanges
      (SCE) in peripheral blood lymphocytes. Here we present data on mercury levels in
      blood and on micronucleus frequencies in peripheral blood lymphocytes of
      fishermen. The range of mercury concentrations in blood was 10.08-304.11 ng/g
      fresh weight, the average was 88.97 +/- 54.09 ng/g. Micronucleus frequency was
      defined with at least 2000 binucleated cells scored for each person; the average
      was 8.74 +/- 2.56 expressed on 1000 binucleated cells. A statistical correlation
      was found between MN frequency and total mercury concentration in blood (p =
      0.00041, r = 0.674), as well as between MN frequency and age (p = 0.017). No
      other parameters taken into account correlated with MN frequency.

PMID- 7506385
TI  - Evaluation of the genotoxic potential of alkyleneamines.
AB  - A series of 6 alkyleneamines [ethylenediamine (EDA), diethylenetriamine (DETA),
      triethylenetetramine (TETA), tetraethylenepentamine (TEPA),
      aminoethylethanolamine (AEEA), and aminoethylpiperazine (AEP)] were evaluated for
      potential genotoxic activity using a battery of in vitro and in vivo assays. Only
      TETA was considered mutagenic in the Salmonella typhimurium mutation assay. All 6
      alkyleneamines tested except AEP were considered inactive in the Chinese hamster
      ovary (CHO) gene mutation assay. AEP was considered inconclusive in this assay.
      In 2 the sister-chromatid exchange (SCE) assay, EDA, DETA and AEEA were inactive
      with or without metabolic activation. TETA, TEPA and AEP were considered active
      in the induction of SCE in CHO cells. With hepatocytes, no positive effects of
      EDA, DETA AEEA and AEP upon unscheduled DNA syntheses (UDS) were noted. However,
      TETA and TEPA produced significant increases in the amount of UDS activity, and
      thus were considered positive in inducing primary DNA damage in this assay. In a
      micronucleus study with Swiss-Webster mice, no clastogenic activity was observed
      with TETA, TEPA and AEP. The overall weight of evidence from the in vitro and in
      vivo tests suggested that EDA, DETA and AEEA were not mutagenic, while TETA was
      mutagenic, and TEPA and AEP had a weak mutagenic potential.

PMID- 7506387
TI  - Mutagenic effects of nitropyrenes in a soybean test system.
AB  - The mutagenic activity of 1-nitropyrene (1-NP), 1,3-dinitropyrene (1,3-DNP), 1,6
      dinitropyrene (1,6-DNP) and 1,8-dinitropyrene (1,8-DNP) was assayed in
      heterozygous soybean plants (Y11y11), based on the appearance of mutational spots
      (yellow, dark green and twin) on the leaves. 1-NP, 1,3-DNP, 1,6-DNP and 1,8-DNP
      were direct-acting mutagens in a soybean test system, and mutagenicity was
      enhanced by addition of pyrene as a precursor. The mutagenicity of dinitropyrenes
      was enhanced by pretreatment with hepatic microsomal fractions of Aroclor 1254
      treated rats. Binary and ternary isomeric mixtures of dinitropyrenes produced
      synergistic mutational response in the test system. The numbers of yellow and
      dark green spots per leaf increased by treatment with nitropyrenes. The frequency
      of twin spots did not change. Nitropyrenes stimulated the induction of forward
      and reverse mutations in soybeans. The number of light green spots (Y11y11) per
      leaf on homozygous soybeans (y11y11) increased markedly by treatment with 1-NP,
      1,3-DNP, 1,6-DNP, and 1,8-DNP. These nitropyrenes would thus appear to cause
      point mutation and segmental loss as major effects.

PMID- 7506386
TI  - Substituent effects on the in vitro and in vivo genotoxicity of 4-aminobiphenyl
      and 4-aminostilbene derivatives.
AB  - 4-Amino-4'-substituted biphenyls and 4-aminostilbenes substituted in the 3' or 4'
      position were studied for their in vitro and in vivo genotoxicity. The in vitro
      mutagenicity of the biphenyls with and without S9 activation was established with
      Salmonella strains TA98 and TA100 and that of the stilbenes with the same strains
      plus TA98/1,8-DNP6. The in vivo genotoxicity assay with both series of compounds
      was for chromosomal aberrations in the bone-marrow cells of mice following
      intraperitoneal administration of the chemicals. Hammett values of substituents,
      partition coefficients and frontier orbital energies (ELUMO and EHOMO) of the
      compounds were used for correlations with mutagenicity. The Salmonella
      mutagenicity in TA98 and TA98/1,8-DNP6 with S9 was correlated to Hammett sigma +
      values for the 4-aminostilbene substituents, showing a strong trend of increasing
      mutagenicity with an increase in the electron-withdrawing capability of the
      substituent. Hydrophobicity of the stilbenes, however, had little effect on their
      relative mutagenicity. The 4-aminobiphenyls showed a correlation between their
      mutagenicity and Hammett sigma + values of their 4'-substituents in stain TA98
      with S9, although the trend was not as strong as for the stilbenes. But unlike
      the stilbenes, TA98 mutagenicity of the biphenyls could also be correlated to
      hydrophobicity, and structure-activity correlations for the biphenyls was
      substantially improved when both sigma + and hydrophobicity data were included.
      For strain TA100 with S9, little correlation was found between mutagenicity of
      the stilbenes and any of the parameters. However, a limited correlation did exist
      between the mutagenicity of the biphenyls and their hydrophobicity. There was
      also limited correlations of the mutagenicity for the stilbenes in TA98 and
      TA98/1,8-DNP6 with S9 to ELUMO or EHOMO. The in vivo genotoxicity results for the
      biphenyls and stilbenes could not be correlated to electronic effects as for the
      in vitro results, nor could they be explained by hydrophobicity. However, it is
      interesting to note that 3'-substituted 4-aminostilbenes were all substantially
      more genotoxic in vivo than their corresponding 4'-substituted counterparts. The
      most genotoxic compound in vivo in either series was 4-aminostilbene which would
      not have been predicted from the in vitro results.

PMID- 7506388
TI  - Chromosomal aberrations in mouse lymphocytes exposed in vitro and in vivo to
      benzidine and 5 related aromatic amines.
AB  - Mouse lymphocytes were exposed in vitro for 2 h or in vivo for 24 h to benzidine
      and related aromatic amines to test for chromosome aberrations (CA) and mitotic
      indices. Uninduced mouse S9 was used to activate the amines for the in vitro
      tests to be consistent with the in vivo tests. Contrary to a previous report, no
      difference could be established in the genotoxicity of benzidine following
      activation with uninduced S9 compared to induced S9. There were concentration
      related increases in CA for benzidine and all the amines in vitro except for 4,4'
      diaminostilbene which exhibited the greatest cellular toxicity towards cultured
      lymphocytes. Benzidine and its derivatives showed significant increases in CA in
      vivo compared to its negative control. The CA values for 4-aminostilbene were
      significantly higher than the other amines in both in vivo and in vitro studies.
      These genotoxicity results for 4-aminostilbene are consistent with our previous
      report of the pronounced CA effects in murine bone-marrow cells but would not be
      predicted from Salmonella mutagenicity tests.

PMID- 7506389
TI  - Altered protein expression detected in the F1 offspring of male mice exposed to
      fission neutrons.
AB  - Liver protein expression in F1 offspring arising from spermatogonia exposed to 60
      cGy of fission spectrum neutrons from the JANUS reactor was compared to that in
      offspring from unexposed spermatogonia by using two-dimensional electrophoresis
      (2DE). Approximately 100 protein spots in 2DE patterns from 167 control offspring
      and 530 offspring from irradiated sires were monitored for quantitative decreases
      of 50%, indicative of mutation events causing the loss of one normal copy of a
      structural gene. Reproducible abnormalities were found only in 3 patterns, all
      from the offspring of neutron-irradiated sires. Two of the three patterns were
      from littermates (brother and sister) and both showed an approximately 70%
      decrease in the amount of liver protein MSN188. The third pattern was from a male
      mouse sired by a different male and showed an approximately 50% decrease in the
      abundance of protein MSN94. The decreased abundance of MSN188 and MSN94 was
      assumed to be due to mutation events referred to as NEUT1 and NEUT2,
      respectively. Sibling crosses between the 2 mice showing the NEUT1 trait produced
      offspring with control, decreased and undetectable levels of MSN188 in a ratio of
      0.25:0.5:0.25. Test crosses between the F1 offspring expressing the NEUT2 trait
      back to C57BL/6JANL mice produced offspring expressing normal or decreased
      amounts of MSN94 in a ratio of 0.5:0.5. Inbreeding of individuals expressing
      decreased amounts of MSN94 produced mice expressing control, decreased amounts,
      or no detectable amount of that protein in a ratio of 0.25:0.5:0.25. These
      results indicate that the decreased abundance of MSN188 or MSN94 originally
      detected in the F1 offspring is due to a genetically transmissible event. Unlike
      the heritable protein changes observed previously in the F1 offspring of sires
      exposed to N-ethyl-N-nitrosourea in which a protein variant was produced, both
      the NEUT1 and NEUT2 mutation events appear to prevent the production of any
      protein product. These 2 mutations may thus represent mutation lesions other than
      point mutations (e.g., deletions or translocations) detectable as quantitative
      changes in protein expression in the F1 generation.

PMID- 7506390
TI  - Chemically-induced aneuploidy in mammalian oocytes.
AB  - The ability of certain chemicals to elevate the frequency of aneuploidy above
      spontaneous levels in mammalian experimental models prompts the concern that a
      similar situation might exist in humans. Validation of experimental models for
      aneuploidy studies is in progress since there is much to be learned about the
      causes and mechanisms of chemically-induced aneuploidy. Several biological
      variables have been shown to influence the results from aneuploidy assays. In
      this review, we examine these variables as they relate to female germ cell
      aneuploid assays. Also, we have found that the aneuploidy results obtained from
      different cell types, sexes, and experimental models cannot necessarily be
      expected to agree due to certain anatomic and physiologic differences and the end
      points measured.

PMID- 7506391
TI  - Bio-anticlastogenic effects of unsaturated fatty acids included in fish oil-
      docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid--in
      cultured Chinese hamster cells.
AB  - Bio-anticlastogenic effects of unsaturated fatty acids--cis-4,7,10,13,16,19
      docosahexaenoic acid (DHA), cis-7,10,13,16,19-docosapentaenoic acid (DPA), and
      cis-5,8,11,14,17-eicosapentaenoic acid (EPA)--on chemically induced chromosome
      aberrations were studied in cultured Chinese hamster cells. The induction of
      chromosome aberrations by the crosslinking agents mitomycin C (MMC) and cisplatin
      (DDP), the SN-1 type alkylating agents N-ethyl-N'-nitro-N-nitrosoguanidine
      (ENNG), methyl nitrosourea (MNU), and ethyl nitrosourea (ENU), and the SN-2 type
      alkylating agent ethyl methanesulfonate (EMS), but not by the SN-1 type
      alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and the SN-2 type
      alkylating agent methyl methanesulfonate (MMS), was suppressed by post-treatment
      with DHA, DPA, and EPA. Since there was no opportunity to inactivate mutagens by
      desmutagenic mechanisms under the post-treatment schedule used, the results
      demonstrate the bio-anticlastogenicity of unsaturated fatty acids. Suppression by
      the unsaturated fatty acids was observed when cells were treated during the G2
      phase, suggesting that G2 events were responsible for the bio-anticlastogenic
      effects. Two saturated fatty acids with the same number of carbons as the studied
      unsaturated fatty acids--docosanoic acid and eicosanoic acid--did not affect
      chromosome aberration induction, suggesting the necessity of unsaturation for
      fatty acid bio-anticlastogenicity.

PMID- 7506392
TI  - Alpha 1-adrenoceptor subtype affinities of drugs for the treatment of prostatic
      hypertrophy. Evidence for heterogeneity of chloroethylclonidine-resistant rat
      renal alpha 1-adrenoceptor.
AB  - We have used radioligand binding and inositol phosphate accumulation studies to
      determine the affinity at mixed alpha 1A- and alpha 1B-adrenoceptors (rat
      cerebral cortex and kidney), alpha 1A-adrenoceptors (rat cerebral cortex and
      kidney following inactivation of alpha 1B-adrenoceptors by chloroethylclonidine
      treatment) and alpha 1B-adrenoceptors (rat spleen) for drugs currently under
      investigation for the treatment of benign prostatic hypertrophy, alfuzosin,
      naftopidil and (-)- and (+)-tamsulosin. Alfuzosin and naftopidil had similar
      affinities in all model systems (approximately 10 nM and 130 nM, respectively)
      and lacked relevant selectivity for alpha 1-adrenoceptor subtypes. Their potency
      to inhibit noradrenaline-stimulated inositol phosphate formation in cerebral
      cortex matched their affinities as determined in the binding studies. Tamsulosin
      had higher affinity at alpha 1A- than at alpha 1B-adrenoceptors, and was slightly
      more potent than alfuzosin and naftopidil at alpha 1B- and considerably more
      potent at alpha 1A-adrenoceptors. However, the interaction of the tamsulosin
      isomers with chloroethylclonidine-insensitive (alpha 1A-like) adrenoceptors was
      complex. A detailed analysis of the tamsulosin data and those obtained with other
      drugs, most notably noradrenaline and oxymetazoline, suggested that
      chloroethylclonidine-insensitive alpha 1-adrenoceptors may be heterogeneous and
      that this heterogeneity may differ between cerebral cortex and kidney of the rat.

PMID- 7506393
TI  - L-type calcium channel activity in human atrial myocytes as influenced by 5-HT.
AB  - 5-Hydroxytryptamine (10 mumol/l; 5-HT) exerted a positive inotropic effect
      associated with an increase in the Ca2+ current (ICa) in the human right atrium.
      For detailed analysis, L-type Ca2+ channel currents were recorded from cell
      attached patches using 100 mmol/l Ba2+ as charge carrier. Ca2+ channel activity
      was identified, first, by burst-like inwardly directed currents and, second, by
      the appearance of long channel openings promoted by Bay K 8644 (1 mumol/l) upon
      repetitive depolarizations from -80 to 0 mV. The unitary conductance of the Ca2+
      channel amounted to 25.8 pS. During superfusion with 5-HT, ensemble averaged
      (mean) current was enhanced by about 60%. The increase in mean current was
      brought about by an increase in the channel availability, defined as the ratio of
      sweeps containing Ca2+ channel activity to the total number of depolarizations.
      The open probability of a single Ca2+ channel within a sweep with channel
      activity, unitary conductance, mean open and mean shut times of the channel,
      however, remained unaffected during superfusion with 5-HT (n = 10). The 5-HT
      induced increase in macroscopic ICa in the human atrium can therefore be
      explained by an enhanced availability of Ca2+ channels to open upon
      depolarization. The observed changes in gating properties of the human Ca2+
      channel by 5-HT are very similar to those which are known from isoprenaline
      induced cAMP-dependent phosphorylation of the Ca2+ channel protein in other
      tissues.

PMID- 7506395
TI  - [Goethe's description of aphasia].

PMID- 7506394
TI  - The role of nitric oxide (NO) in 5-HT-induced relaxations of the guinea-pig
      stomach.
AB  - In a previous study we showed that the relaxations induced after vagal
      stimulation of the guinea-pig stomach are mediated via nitric oxide (NO) or a NO
      related substance. Intra-arterial injection (i.a.) of 5-hydroxytryptamine (5-HT)
      also induced relaxations in the guinea-pig stomach. Since it has been shown that
      in the guinea-pig colon 5-HT-induced relaxations are mediated via NO the aim of
      this study was to establish whether NO is involved in the 5-HT-induced
      relaxations in the guinea-pig stomach. Intra-arterial injection of 5-HT induced
      dose-dependent relaxations of the stomach. Since atropine and alpha- and beta
      adrenoceptor blocking agents did not influence the relaxation and since
      tetrodotoxin (TTX) blocked the relaxations, this effect is mediated via NANC
      neurons. Administration of a NO-synthase-inhibitor NG-nitro-L-arginine (L-NNA)
      concentration-dependently reduced the 5-HT-induced relaxations. Haemoglobin (a NO
      scavanger) did not affect the relaxations to 5-HT, while addition of methylene
      blue, an inhibitor of soluble guanylate cyclase, reduced the relaxations by 50%.
      Addition of an opioid receptor agonist (loperamide), a 5-HT1 antagonist
      (methiothepin or metergoline) or a 5-HT4 receptor agonist (cisapride) or 
      antagonist (tropisetron in micromolar concentrations) inhibited the 5-HT-induced
      relaxations. Neither the 5-HT4 receptor agonist renzapride, nor the novel 5-HT4
      receptor antagonist SDZ 205-557, affected the relaxations to 5-HT.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7506396
TI  - Anti-vimentin staining in muscle pathology.
AB  - The intermediate filaments of immature muscle fibres contain desmin and vimentin;
      vimentin is lacking in mature fibres. Regenerating fibres react with anti
      vimentin antibodies and more intensely for desmin than mature fibres. The aim of
      the present study was to evaluate anti-vimentin staining for muscle pathology.
      Anti-vimentin-reactive fibres were found in 40 of 89 biopsies assessed. Fifteen
      patients with progressive destructive myopathy, infantile spinal muscular
      atrophy, clinically suspected Leigh's disease or unclassifiable congenital
      myopathy had between 1% and 95% vimentin-positive fibres. Less than 1% positive
      fibres were found in 25 patients with neuropathy with secondary myopathy or
      chronic myopathic conditions. Vimentin-positive fibres were lacking in 20 normal
      biopsies, in eight biopsies with neuropathic and in 21 biopsies with mild or non
      destructive myopathic changes. We conclude that staining with anti-vimentin
      antibodies is a useful indicator for muscle fibre regeneration; it may help
      establish the diagnosis in infantile spinal muscular atrophy when the
      histopathology is non-characteristic. The high incidence of reactive fibres in
      some congenital or early-onset disorders may indicate developmental arrest.

PMID- 7506397
TI  - Gadolinium-enhanced MRI in cerebral Whipple's disease.
AB  - Confusion developed in a 44-year-old man, who had diarrhoea and weight loss for
      three months. Jejunal biopsy showed infiltration by PAS-positive macrophages,
      indicating Whipple's disease. Cranial MRI disclosed multiple lesions mainly in
      the white matter and grey-white matter junction better demonstrated after
      gadolinium injection.

PMID- 7506398
TI  - Molecular evidence for nitric oxide-mediated motor neuron development.
AB  - The complex morphological, electrophysiological and molecular properties of the
      adult vertebrate nervous system emerge over an extended period in prenatal and
      early postnatal life. Numerous studies have shown that synaptic activity plays a
      key role in the postnatal acquisition of mature neuronal phenotype. The cellular
      and molecular mechanisms subserving activity-dependent development are largely
      unknown. Several lines of evidence suggest that a rise in intracellular Ca2+ as a
      consequence of synaptic activity may regulate neuronal differentiation through
      its interactions with calcium-activated signal transduction molecules such as
      calcium/calmodulin kinase type II, protein kinase C or nitric oxide synthase
      (NOS). The aim of the present study is to identify potential signal transduction
      events subserving postnatal motor neuron development. Here we show that NOS
      antagonists block the molecular maturation of motor neurons and this effect is
      likely to be mediated by a subpopulation of ventral horn cells that express NOS
      transiently during early postnatal life. These results suggest that the local
      production of nitric oxide within the ventral horn may contribute to a late phase
      in motor neuron differentiation.

PMID- 7506399
TI  - Histochemical localization of NADPH-dependent diaphorase (nitric oxide synthase)
      activity in vascular endothelial cells in the rat brain.
AB  - This study investigated the localization of NADPH-dependent diaphorase activity
      within vascular endothelial cells in the rat brain. Light microscope observations
      showed that in addition to neurons and neuronal processes stained histochemically
      for NADPH-dependent diaphorase activity, endothelial cells in many medium to
      large diameter (20-100 microns) blood vessels were also stained. These vessels
      were either attached to the pial surface or contained within the substance of the
      tissue. In vascular endothelia, the formazan end-product of the diaphorase
      reaction was deposited as discrete clusters of darkly stained punctae that were
      located around the nucleus of these cells. Correlated light- and electron
      microscopical examination revealed that the sites of formazan deposition occurred
      in regions of endothelial cytoplasm devoid of smooth and rough endoplasmic
      reticulum and of mitochondria. Since endothelial NADPH dependent diaphorase
      activity co-localizes with the activity of nitric oxide synthase (the synthetic
      enzyme for nitric oxide) these observations suggest that in vascular endothelial
      cells nitric oxide synthase may be a highly localized soluble cytosolic enzyme
      not structurally associated with any subcellular organelle. In addition, specific
      regions of the smooth muscle cells encircling the larger diameter blood vessels
      clearly demonstrated NADPH dependent diaphorase activity. Unmyelinated fibres and
      fibre-plexi surrounding blood vessels on the pial surface were also stained. The
      results of this study show specific NADPH dependent diaphorase activity in
      vascular endothelial cells in the rat brain. Therefore, together with neurons,
      endothelial cells may control nitric oxide-dependent vasodilation thereby
      regulating local blood flow in the brain.

PMID- 7506400
TI  - Argon laser scatter photocoagulation in treatment of branch retinal vein
      occlusion. A prospective clinical trial.
AB  - The objective of this prospective study was to ascertain whether scatter argon
      laser photocoagulation to the involved sector in major branch retinal vein
      occlusion and ischemic hemicentral retinal vein occlusion (a) prevents
      development of retinal and/or optic disk neovascularization and vitreous
      hemorrhage, and (b) affects visual acuity, visual fields and macular retinal
      lesions. The study was done in 271 eyes allocated to either treated (n = 61 eyes)
      or untreated (n = 210) groups. In this study, on an average follow-up of 3.6
      years, the laser treatment (1) significantly reduced the risk of development of
      retinal neovascularization and vitreous hemorrhage, (2) did not affect the visual
      acuity and macular retinal lesions, and (3) produced a significant worsening in
      the peripheral visual fields compared to the untreated eyes. In view of our
      findings, we recommend that argon laser photocoagulation treatment should be
      given only when neovascularization is seen and not otherwise, because in the
      latter case, its detrimental effects may outweigh its beneficial ones.

PMID- 7506401
TI  - [Leukocyte adhesion molecules in chronic inflammatory diseases of the cornea].
AB  - Using immunohistochemical techniques, we investigated the expression of leukocyte
      adhesion molecules-intercellular adhesion molecule-1 (ICAM-1), E-selectin
      (endothelial leukocyte adhesion molecule-1), and vascular cell adhesion molecule
      1 (VCAM-1)--in various chronic inflammatory corneal diseases of different
      etiology. ICAM-1 was focally expressed on epithelial cells and showed an
      increased expression, on keratocytes, corneal endothelial cells, and vascular
      endothelial cells. E-selectin was present on vascular endothelial cells of
      several corneas, while VCAM-1 was found particularly on macrophages and only
      sporadically on vascular endothelial cells. Our results suggest that ICAM-1, E
      selectin, and VCAM-1 may be involved in the pathogenesis of various chronic
      inflammatory corneal diseases, particularly in the selective recruitment of
      different leukocyte populations.

PMID- 7506402
TI  - Comparisons of photocoagulation treatment in exudative age-related macular
      degeneration with the blue-green argon, green argon and red krypton laser
      wavelengths.
AB  - Between November 1975 and December 1989, we examined 1,540 patients with age
      related macular degeneration (ARMD). 297 eyes of 270 of these patients received
      photocoagulation treatment (from L.S.A.) for exudative ARMD, including choroidal
      neovascular membranes (CNVMs) and retinal pigment epithelial detachment.
      Initially, only the blue-green argon laser was available. From 1983 onwards we
      could choose between the blue-green argon, green argon and red krypton laser
      wavelengths. The 270 treated patients were followed for a minimum of 6 and a
      maximum of 168 months posttreatment (median 16 months). Of the 297 eyes, 138
      received treatment with the blue-green argon, 36 with the green argon and 123
      with the red krypton laser. Eyes with subfoveal and juxtafoveal NVMs were treated
      with the krypton laser. Also assigned to krypton photocoagulation were
      extrafoveal NVMs accompanied by hemorrhage. There was no statistical difference
      in the results of the three treatment modalities as judged by visual acuity. But,
      green argon is preferable to blue-green argon since it is absorbed less by the
      xantophyll pigment. On the other hand, krypton laser appears to be at least as
      effective as green argon in extrafoveal neovascularization and is certainly the
      treatment of choice in subfoveal and juxtafoveal NVMs.

PMID- 7506403
TI  - Comparison between efficacy of full- and mild-scatter (panretinal)
      photocoagulation on the course of diabetic rubeosis iridis.
AB  - The study enrolled 59 eyes with rubeosis iridis and proliferative diabetic
      retinopathy. The efficacies of two types of panretinal photocoagulation ('full'
      and 'mild' scatter) on the course of diabetic rubeosis iridis were compared. The
      mean posttreatment follow-up period was 22 +/- 4.8 months. After application of
      full-scatter photocoagulation (1,200-1,600 spots) in 27 eyes, rubeosis iridis
      regressed in 70.4% cases, remained unchanged in 14.8% and deteriorated in 14.8%.
      After mild-scatter photo-coagulation (400-650 spots) in 32 treated eyes, rubeosis
      iridis regressed in 37.5% cases, 34.4% was unchanged, while deterioration was
      found in 28.1%. A better therapeutic effect of panretinal photocoagulation in
      regression of diabetic rubeosis iridis was obtained, if the total dose of the
      applied laser spots was higher.

PMID- 7506404
TI  - Serotonin and acetylcholine: further analysis of praziquantel-induced contraction
      of magnesium-paralysed Schistosoma mansoni.
AB  - The nature of stimulus-induced flaccid paralysis produced in Mg(2+)-paralysed
      Schistosoma mansoni was investigated. Serotonin induced a dose-dependent,
      heterologous flaccid paralysis with an IC50 of 600 nM. This flaccid paralysis was
      a function of the extracellular Mg2+:Ca2+ ratio and was reversible. Tonic
      contractions produced by phorbol-12,13-dibutyrate or 60 mM K+ were reversed by
      the application of serotonin and flaccid paralysis was induced. These actions of
      serotonin were mimicked by forskolin and synergized by IBMX but the potassium
      channel blocker, 3,4-DAP, did not produce flaccid paralysis. When Mg(2+)
      paralysed parasites were stimulated with 3,4-DAP, IBMX produced a dose-dependent
      flaccid paralysis with an IC50 of 11 microM. Membrane permeable analogues of cAMP
      and cGMP did not synergize with IBMX. Cholinergic agonists, but not other
      inhibitory substances, prevented the serotonin- and forskolin-induced and the
      IBMX-synergized flaccid paralysis but not that produced by praziquantel. The
      possible interactions of these agents with the muscle are discussed.

PMID- 7506405
TI  - Hepatic fibrosis and gene expression changes induced by praziquantel treatment
      during immune modulation of Schistosoma japonicum infection.
AB  - In the present study fibrogenic gene expression was determined in murine
      Schistosoma japonicum infection during the progression of immune modulation of
      infection and following chemotherapy during the course of immune modulation.
      Histomorphometric analysis of granuloma size and collagen deposition revealed
      peak granuloma size in acute infection (5 weeks) and peak hepatic collagen
      content at 16 weeks of infection. Peak Type I collagen gene expression was
      concomitant with TGF-beta 1 gene expression at 8-11 weeks. Chemotherapy during
      either acute (9 weeks) or chronic (24, 28 weeks) infection resulted in increased
      collagen deposition and increased gene expression of Type I collagen and TGF-beta
      1. However, chemotherapy at 14-16 weeks resulted in decreased levels of TGF-beta
      1 gene expression and essentially minimal change in Type I collagen deposition
      and gene expression. These data indicate that chemotherapy of schistosomiasis
      japonica does not reverse hepatic fibrogenesis when administered in acute
      infection-when granuloma size is maximal-or in chronic infection. However, a
      beneficial effect on hepatic fibrogenesis is seen when chemotherapy is
      administered at 14-16 weeks post-infection, a time of decreasing granuloma size
      and maximal hepatic collagen content. Thus the ability to reverse schistosomal
      induced hepatic fibrogenesis by chemotherapy may depend on disease stage.

PMID- 7506407
TI  - Pediatric hypospadias surgery.
AB  - The pediatric health care practitioner is a valuable resource of information for
      the family of an infant with hypospadias prior to the child and family's first
      visit to the pediatric urologist. Pediatric nurses are involved in the
      preoperative and postoperative care of children with surgical correction of
      hypospadias and should be aware of the newest advances in surgical techniques and
      improvements in postoperative care, particularly dressings and urethral stents.
      These advances have improved the outcome for children, including diminished pain
      and discomfort, minimal hospital stay and decreased complications. Minimal
      postoperative intervention is required. The current management of these children
      will ensure the optimum resolution with minimum physical and psychological
      problems for the child and family.

PMID- 7506406
TI  - Cytoskeleton-associated antigens from African trypanosomes are recognized by self
      reactive antibodies of uninfected mice.
AB  - Serum from uninfected mice of different strains, as well as from germ-free
      animals, contains antibodies which react specifically with at least two
      trypanosomal proteins, I/6 and MARP1. These antibody populations are highly
      specific for the respective proteins, are of similar affinity as hyperimmune
      antibodies, and consist of IgM as well as IgG isotypes. Hyperimmune antibody
      raised against the cross-reacting trypanosomal protein I/6 detects a 60 kDa
      protein in mouse 3T6 cells, which is a component of the fibroblast cytoskeleton.

PMID- 7506408
TI  - Expanding multiple marker screening for Down's syndrome to include Edward's
      syndrome.
AB  - Information on maternal age and maternal serum alpha-fetoprotein, unconjugated
      oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was used to
      investigate retrospectively the effect of estimating Edward's syndrome risk in
      women having multi-marker screening for Down's syndrome. The screened population
      comprised 15 pregnancies affected by Edward's syndrome, 15 with Down's syndrome
      and 5472 unaffected pregnancies. The use of all three markers to estimate
      Edward's syndrome risk would have led to the detection of 10-12 (67-80 per cent)
      cases with a false-positive rate of 0.3-0.6 per cent depending on the risk cut
      off. A further case would have been detected as a result of screening for Down's
      syndrome alone. Similar results were obtained when the Edward's syndrome risk was
      based on uE3 and hCG only. These data suggest that extending Down's syndrome
      screening to include Edward's syndrome risk will yield a high detection rate with
      only a small increase in the false-positive rate.

PMID- 7506409
TI  - Calculating amniotic fluid alpha-fetoprotein median values in the first
      trimester.

PMID- 7506410
TI  - Interleukin 1 induces expression of the human immunodeficiency virus alone and in
      synergy with interleukin 6 in chronically infected U1 cells: inhibition of
      inductive effects by the interleukin 1 receptor antagonist.
AB  - In the present study we have observed that interleukin (IL) 1 alpha or IL-1 beta
      directly induced expression of human immunodeficiency virus (HIV) in the latently
      infected human promonocytic cell line U1. In addition, IL-1 synergized with IL-6,
      but not with tumor necrosis factor, in the upregulation of virus expression in U1
      cells as measured by accumulation of steady-state mRNAs and production of reverse
      transcriptase activity. The HIV inductive effect of IL-1 was blocked by
      transforming growth factor beta, anti-IL-1 antibodies, or monoclonal antibodies
      directed to the type 1, but not to the type 2, cell surface receptor for IL-1;
      the latter actually caused enhancement of the IL-1-mediated effect. Unlike tumor
      necrosis factor alpha, IL-1 either alone or in combination with IL-6 did not
      induce activation of the transcription activating factor NF-kappa B above the
      constitutive levels of unstimulated U1 cells. Finally, the IL-1 receptor
      antagonist effectively blocked IL-1-mediated direct and synergistic inductive
      effects on virus production. Thus, IL-1 may be an important mediator of HIV
      expression, and blocking of IL-1 expression and/or its effects may have a
      potential therapeutic role in the inhibition of HIV expression in infected
      individuals.

PMID- 7506411
TI  - Structure from function: screening structural models with functional data.
AB  - Structural constraints derived from different antibody epitopes on human growth
      hormone (hGH) were used to screen three-dimensional models of hGH that were
      generated by computer algorithms. Previously, alanine-scanning mutagenesis
      defined the residues that modulate binding to 21 different monoclonal antibodies
      to hGH. These functional epitopes were composed of 4-14 side chains whose alpha
      carbons clustered within 4-23 A. Distance and topographic constraints for these
      functional epitopes were virtually the same as constraints derived from known x
      ray structures of protein-antigen complexes. The constraints were used to
      evaluate about 1400 models of hGH that were computer-generated by a secondary
      structure prediction and packing algorithm. On average each functional epitope
      reduced the number of models in the pool by a factor of 2, so that 8 monoclonal
      antibodies could reduce the number of possible models to < 10. The average root
      mean-square deviation of alpha-carbon coordinates between the x-ray structure and
      either the pool of starting models or final models ranged from 13 to 16 A or 4 to
      7 A, respectively, depending on the pool of starting models and the level of
      constraints imposed. All of the final models had the correct folding topography,
      and the best model was within 3.8 A root-mean-square deviation of the x-ray
      coordinates. This model was as close as it could have been because the models
      were built by using ideal helices and those in the x-ray structure are not. Our
      studies suggest that epitope mapping data can effectively screen structural
      models and, when coupled to predictive algorithms, can help to generate low
      resolution models of a protein.

PMID- 7506412
TI  - Ligand-induced activation of chimeric receptors between the erythropoietin
      receptor and receptor tyrosine kinases.
AB  - Ligand-induced dimerization is a key step in the activation of receptor tyrosine
      kinases, including the epidermal growth factor receptor, stem cell factor
      receptor (c-kit), and colony-stimulating factor 1 receptor (c-fms). The
      erythropoietin receptor (EPOR), a member of the cytokine receptor family,
      contains no kinase motif and its activation mechanism remains unclear. Here we
      show that chimeric receptors carrying the extracellular domain of the epidermal
      growth factor receptor or c-kit linked to the cytoplasmic domain of the EPOR,
      transmitted epidermal growth factor or stem cell factor-dependent proliferation
      signals in an interleukin 3-dependent cell line. The chimeric receptors as well
      as the wild-type EPOR also mediated the ligand-induced tyrosine phosphorylation
      of a set of similar proteins. Moreover, erythropoietin triggered mitogenic
      signals of chimeric receptors carrying the extracellular domain of the EPOR
      linked to the tyrosine kinase of c-fms. These data demonstrate the
      interchangeability of domains between two distinct receptor families and suggest
      that ligand-induced dimerization is a key step in activating the EPOR.

PMID- 7506414
TI  - The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping
      domains.
AB  - The DNA binding activity of transcription factor AP-1 is regulated in vitro by a
      posttranslational mechanism involving reduction/oxidation (redox). Redox
      regulation is mediated by a conserved cysteine residue in the DNA-binding domain
      of Fos and Jun. Previously, we demonstrated that a DNA repair protein, Ref-1,
      could stimulate the DNA binding activity of Fos-Jun dimers by reducing this
      cysteine residue. To examine the relationship between the redox and repair
      functions of Ref-1, we generated a series of deletion mutants. Analysis of the
      truncated proteins in vitro revealed that the redox and repair activities are
      encoded by distinct regions of Ref-1. Sequences in the N-terminal domain of Ref-1
      that are not present in functionally related proteins from other organisms are
      required for the redox activity, whereas the DNA repair activity requires
      conserved C-terminal sequences. Chemical alkylation or oxidation of cysteine
      sulfhydryls inhibits the redox activity of Ref-1 without affecting its DNA repair
      activity. Crosslinking studies suggest that a direct cysteine-mediated
      interaction occurs between Ref-1 and Jun.

PMID- 7506413
TI  - Epidermal growth factor-receptor mutant lacking the autophosphorylation sites
      induces phosphorylation of Shc protein and Shc-Grb2/ASH association and retains
      mitogenic activity.
AB  - Epidermal growth factor (EGF) receptor (EGFR) can induce cell growth and
      transformation in a ligand-dependent manner. To examine whether the
      autophosphorylation of EGFR correlates with the capacity of the activated EGFR to
      induce cell growth and transformation, we truncated the human EGFR just after
      residue 1011, removing all three major autophosphorylation sites (DEL1011).
      Further, a point mutation was introduced at another autophosphorylation site, Tyr
      992-->Phe (DEL1011+F992). The wild-type and mutant receptors were stably
      expressed in a NIH 3T3 variant cell line that expresses an extremely low level of
      endogenous EGFR and does not grow with EGF. As expected, DEL1011 and DEL1011+F992
      were found to be severely impaired in EGF-induced autophosphorylation, due to the
      deletion of the appropriate target tyrosines. However, mutant receptors still
      could induce EGF-dependent DNA synthesis, morphological transformation, and
      anchorage-independent growth, although the extent of these was significantly
      reduced when compared with wild-type EGFR. EGF-induced tyrosine phosphorylation
      of Ras-GTPase activating protein-associated protein p62 and phospholipase C gamma
      1 was dramatically reduced in the cells expressing DEL1011 and DEL1011+F992. On
      the other hand, tyrosine phosphorylation of Shc, complex formation of Shc
      Grb2/Ash, and activation of microtubule-associated protein kinase were still
      fully induced upon EGF stimulation without binding of Shc or Grb2/Ash to the
      mutant receptor. Thus, tyrosine phosphorylation of Shc may play a crucial role
      for activating Ras and generating mitotic signals by the activated EGFR mutant.

PMID- 7506415
TI  - Epithelial autotoxicity of nitric oxide: role in the respiratory cytopathology of
      pertussis.
AB  - Bordetella pertussis releases a specific peptidoglycan fragment known as tracheal
      cytotoxin (TCT) that reproduces the respiratory epithelial cytopathology of
      whooping cough (pertussis). In vitro, TCT inhibits DNA synthesis in hamster
      trachea epithelial cells and causes specific destruction of ciliated cells in
      explants of human and hamster respiratory epithelium. We have recently
      demonstrated that TCT triggers production of intracellular interleukin 1 by
      respiratory epithelial cells, and this cytokine may act as an intermediate signal
      in the generation of TCT toxicity. Here we report the identification of a
      subsequent critical step in this pathway: induction of nitric oxide synthesis in
      the respiratory epithelium. The toxic effects of nitric oxide are consistent with
      spectroscopic evidence of the formation of iron-dinitrosyl-dithiolate complexes
      in TCT-treated cells. Aconitase, with its iron-sulfur center, is one expected
      target of nitric oxide, and TCT inhibited 80% of the activity of this enzyme in
      respiratory epithelial cells. The deleterious effects of TCT and interleukin 1
      were dramatically attenuated by the nitric oxide synthase inhibitors NG
      monomethyl-L-arginine and aminoguanidine. These results indicate that nitric
      oxide mediates the toxicity of TCT for the respiratory epithelium, thus
      implicating a central role for nitric oxide in the pathogenesis of pertussis.

PMID- 7506416
TI  - Attenuation of the induction of nitric oxide synthase by endogenous
      glucocorticoids accounts for endotoxin tolerance in vivo.
AB  - An enhanced formation of nitric oxide (NO) due to induction of a calcium
      independent (inducible) NO synthase (iNOS) contributes importantly to the
      cardiovascular failure caused by bacterial endotoxin. Repeated challenges with
      small doses of endotoxin result in tolerance to both peripheral vascular failure
      and death caused by subsequent injection of a higher dose of endotoxin. Here we
      investigate whether tolerance to endotoxin is associated with a lack of induction
      of iNOS in vivo and whether endogenous glucocorticoids play a role in the
      development of endotoxin tolerance. In anesthetized rats, i.v. administration of
      Escherichia coli endotoxin [lipopolysaccharide (LPS); 2 mg.kg-1] resulted in a
      prolonged decrease in mean arterial blood pressure (MAP) and hyporeactivity to
      the contractile responses elicited by norepinephrine (NE; 10 nM) in aortic rings
      ex vivo. Hyporeactivity to NE was partially reversed by NG-nitro-L-arginine
      methyl ester (0.3 mM) in vitro, suggesting that an enhanced formation of NO
      contributes to this hyporeactivity. There was a substantial increase in the
      activity of iNOS in the lung 3 h after i.v. injection of LPS (0.2 +/- 0.1 to 6.6
      +/- 0.6 pmol.mg-1.min-1; n = 5; P < 0.01). Rats injected i.p. with LPS (0.5 mg.kg
      1) for 4 consecutive days became tolerant to an i.v. injection of LPS (2 mg.kg-1)
      in that both hypotension and vascular hyporeactivity to NE were significantly
      attenuated. Moreover, in these endotoxin-tolerant rats, the induction of iNOS by
      LPS in the lung was attenuated by 63% +/- 6%. Injection of LPS caused a 9-fold
      increase in plasma corticosterone (CCS) levels within 2 h and CCS levels remained
      significantly elevated 6 and 24 h after LPS. Animals rendered tolerant to
      endotoxin by administration of a low dose of LPS (0.5 mg.kg-1, i.p.) for 4 days
      still had a 6-fold increase in plasma CCS levels 24 h after the last injection of
      LPS. When endotoxin-tolerant rats were treated with the glucocorticoid receptor
      antagonist RU 486 (50 mg.kg-1, p.o. 3 h prior to LPS), there was a restoration of
      the effects of LPS (2 mg.kg-1, i.v.) in causing hypotension, vascular
      hyporeactivity to NE, and iNOS induction in the lung. However, in control rats RU
      486 enhanced neither the decrease in MAP nor the induction of iNOS in response to
      LPS (2 mg.kg-1, i.v.). Thus, cardiovascular tolerance to endotoxin is accompanied
      and explained by reduced induction of iNOS in vivo due to the elevation of
      endogenous glucocorticoid levels.

PMID- 7506417
TI  - A minority of carcinoma cells producing acidic fibroblast growth factor induces a
      community effect for tumor progression.
AB  - It is generally accepted that primary tumors become heterogeneous as a
      consequence of tumor-cell genetic instability. Clonal dominance has been shown to
      occur in some experimental models allowing a subpopulation of cells to overgrow
      the primary heterogeneous tumor and to metastasize. Alternatively, interactions
      among coexisting tumor subpopulations may contribute to the emergence of a
      malignant invasive primary solid tumor. We asked the question whether emergence
      of carcinoma cells producing a growth/dissociating factor within a tumor cell
      population may be a determinant for tumor progression and for clonal dominance.
      To mimic such a situation, we have investigated the impact of tumor subpopulation
      heterogeneity in an in vivo model in which mixtures of carcinoma cells that
      differ in their ability to produce acidic fibroblast growth factor are injected
      into nude mice. Our data indicate that a growth-factor-producing cell
      subpopulation can confer increased tumorigenicity to an entire cell population
      and subsequently elicit a shorter delay for appearance of metastasis. A community
      effect via cell interactions may account for a heterogeneous tumor cell
      population rather than clonal dominance during progression of certain tumor
      types.

PMID- 7506418
TI  - Functional communication in the recognition of tRNA by Escherichia coli
      glutaminyl-tRNA synthetase.
AB  - Wild-type Escherichia coli glutaminyl-tRNA synthetase (GlnRS; EC 6.1.1.18) poorly
      aminoacylates opal suppressors (GLN) derived from tRNA(Gln). Mutations in glnS
      (the gene encoding GlnRS) that compensate for impaired aminoacylation were
      isolated by genetic selection. Two glnS mutants were obtained by using opal
      suppressors differing in the nucleotides composing the base pair at 3.70: glnS113
      with an Asp-235-->Asn change selected with GLNA3U70 (GLN carrying G3-->A and C70-
      >U changes), and glnS114 with a Gln-318-->Arg change selected with GLNU70 (GLN
      carrying a C70-->U change). The Asp-235-->Asn change was identified previously by
      genetic selection. Additional mutants were isolated by site-directed mutagenesis
      followed by genetic selection; the mutant enzymes have single amino acid changes
      (Lys-317-->Arg and Gln-318-->Lys). A number of mutants with no phenotype also
      were obtained randomly. In vitro aminoacylation of a tRNA(Gln) transcript by
      GlnRS enzymes with Lys-317-->Arg, Gln-318-->Lys, or Gln-318-->Arg changes shows
      that the enzyme's kinetic parameters are not greatly affected by the mutations.
      However, aminoacylation of a tRNA(Gln) transcript with an opal (UCA) anticodon
      shows that the specificity constants (kcat/Km) for the mutant enzymes were 5-10
      times above that of the wild-type GlnRS. Interactions between Lys-317 and Gln-318
      with the inside of the L-shaped tRNA and with the side chain of Gln-234 provide a
      connection between the acceptor end-binding and anticodon-binding domains of
      GlnRS. The GlnRS mutants isolated suggest that perturbation of the interactions
      with the inside of the tRNA L shape results in relaxed anticodon recognition.

PMID- 7506419
TI  - Anergic T-lymphocyte clones have altered inositol phosphate, calcium, and
      tyrosine kinase signaling pathways.
AB  - Full activation of TH1 helper T lymphocytes requires ligation of the specific T
      cell antigen receptor (TCR) and a second signal provided by costimulator
      molecule(s) expressed on particular antigen-presenting cells. Stimulation via the
      TCR complex alone generates a subsequent unresponsive state characterized by an
      inability to produce interleukin 2. We report here that such anergic cells
      exhibit multiple alterations in TCR-associated signaling. The basal levels of
      intracellular free calcium and phosphatidylinositol 1,4,5-trisphosphate are
      elevated in anergic cells, and the levels fail to increase significantly upon
      subsequent restimulation. Examination of phospholipase C-gamma 1 reveals evidence
      for post-translational modification, correlating with increased tyrosine
      phosphorylation of the molecule. Tyrosine phosphorylation of additional
      substrates identified from whole-cell lysates also is altered compared to
      untreated cells, suggesting a modification in net tyrosine kinase activity.
      Although the level of kinase activity present in TCR/CD3 or Lck
      immunoprecipitates is modestly altered after induction of anergy, there is a
      dramatic increase in specific Fyn-associated tyrosine kinase activity in anergic
      cells and increased phosphorylation of a 110-kDa protein that is
      coimmunoprecipitated with Fyn. These results are consistent with a model in which
      anergic TH1 lymphocytes display a fundamental alteration in TCR-mediated tyrosine
      kinase activity, associated with changes in phospholipase C-gamma 1, inositol
      phosphates, and intracellular free calcium.

PMID- 7506420
TI  - Cellular adaptation to opiates alters ion-channel mRNA levels.
AB  - The chronic use of several drugs, including opiates, results in the stereotypical
      behaviors characteristic of addiction. Alterations in gene expression have been
      associated with the use of these addictive drugs. Previous studies, however, have
      been limited to describing changes in amounts of individual mRNAs from single
      tissue samples. Cellular adaptation to opiates, reflected in the regulation of
      the expression of many different mRNAs, seems likely to contribute to the
      complicated behaviors of addiction. The present studies examined coordinate
      alterations in the amounts of multiple mRNAs in the rat striatum and in NG108-15
      cells after opioid stimulation or the precipitated withdrawal of opioid use. The
      experimental approach combined amplification of the poly(A)+ RNA population with
      reverse Northern blot analysis to simultaneously characterize the relative
      changes in several mRNAs. Morphine treatment of rats for 5 days was associated
      with a reduction in the amount of striatal RNA for the voltage-sensitive K+
      channel without significant changes in other ion channels. In NG108-15 cells
      stimulation with the delta-opiate receptor agonist [D-Ala2,D-Leu5]enkephalin
      (DADLE) alone and followed by naloxone (precipitated withdrawal) caused relative
      changes in the abundances of several mRNAs. The composite effects of alterations
      in the abundance of multiple mRNAs (and the proteins they encode) in response to
      opioid use likely contribute to the development and maintenance of opiate
      mediated behaviors.

PMID- 7506421
TI  - DNA bound by the Oxytricha telomere protein is accessible to telomerase and other
      DNA polymerases.
AB  - Macronuclear telomeres in Oxytricha exist as DNA-protein complexes in which the
      termini of the G-rich strands are bound by a 97-kDa telomere protein. During
      telomeric DNA replication, the replication machinery must have access to the G
      rich strand. However, given the stability of telomere protein binding, it has
      been unclear how this is accomplished. In this study we investigated the ability
      of several different DNA polymerases to access telomeric DNA in Oxytricha
      telomere protein-DNA complexes. Although DNA bound by the telomere protein is not
      degraded by micrococcal nuclease or labeled by terminal
      deoxynucleotidyltransferase, this DNA serves as an efficient primer for the
      addition of telomeric repeats by telomerase, a specialized RNA-dependent DNA
      polymerase (ribonucleoprotein reverse transcriptase), EC 2.7.7.49. Moreover, in
      the presence of a suitable complementary C-rich DNA template, AMV reverse
      transcriptase and the E. coli Klenow fragment will also elongate DNA bound by the
      telomere protein. These findings indicate that the 3' terminus and the Watson
      Crick base pairing positions are exposed in the protein complex. We propose that
      the telomere protein can serve a dual role at the telomere by protecting the DNA
      phosphate backbone from degradation while simultaneously exposing the DNA bases
      for replication.

PMID- 7506422
TI  - Involvement of pp60c-src with two major signaling pathways in human breast
      cancer.
AB  - The phosphotyrosine residues of receptor tyrosine kinases serve as unique binding
      sites for proteins involved in intracellular signaling, which contain SRC
      homology 2 (SH2) domains. Since overexpression or activation of the pp60c-src
      kinase has been reported in a number of human tumors, including primary human
      breast carcinomas, we examined the interactions of the SH2 and SH3 domains of
      human SRC with target proteins in human carcinoma cell lines. Glutathione S
      transferase fusion proteins containing either the SH2, SH3, or the entire SH3/SH2
      region of human SRC were used to affinity purify tyrosine-phosphorylated proteins
      from human breast carcinoma cell lines. We show here that in human breast
      carcinoma cell lines, the SRC SH2 domain binds to activated epidermal growth
      factor receptor (EGFR) and p185HER2/neu. SRC SH2 binding to EGFR was also
      observed in a nontumorigenic cell line after hormone stimulation. Endogenous
      pp60c-src was found to tightly associate with tyrosine-phosphorylated EGFR.
      Association of the SRC SH2 with the EGFR was blocked by tyrosyl phosphopeptides
      containing the sequences surrounding tyrosine-530, the regulatory site in the SRC
      C terminus, or sequences surrounding the major sites of autophosphorylation in
      the EGFR. These results raise the possibility that association of pp60c-src with
      these receptor tyrosine kinases is an integral part of the signaling events
      mediated by these receptors and may contribute to malignant transformation.

PMID- 7506423
TI  - AMPA/kainate antagonists in the nucleus accumbens inhibit locomotor stimulatory
      response to cocaine and dopamine agonists.
AB  - The purpose of this study was to determine whether AMPA/kainate excitatory amino
      acid receptors in the nucleus accumbens (NAc) play a role in the locomotor
      stimulation produced by cocaine and dopamine receptor agonists. The stimulation
      of locomotor activity produced by the systemic administration of cocaine was
      markedly attenuated by either the D1 receptor antagonist SCH23390 or the D2
      receptor antagonist eticlopride administered directly into the NAc. This
      indicates that both dopaminergic receptor subtypes in the NAc are involved in the
      motor stimulant response to cocaine. The intra-accumbens administration of DNOX
      or GAMS, which have been shown to inhibit the locomotor stimulation produced by
      the excitatory amino acid agonist AMPA, antagonized the locomotor stimulant
      response to cocaine administered either systemically or directly into the NAc.
      DNOX and GAMS also inhibited the stimulation of locomotor activity produced by
      the coinjection of the D1 agonist SKF38393 and the D2 agonist quinpirole injected
      into the NAc of normal animals and of animals pretreated with reserpine. These
      results suggest that the activation of AMPA/kainate receptors in the NAc plays an
      important role in the locomotor stimulation produced by cocaine and directly
      acting dopaminergic receptor agonists. The effects produced by the activation of
      these receptors is independent of endogenous dopamine stores, suggesting that
      these receptors are located postsynaptic to the dopaminergic nerve terminals.

PMID- 7506424
TI  - Allosteric interaction of dynorphin and myelin basic protein with muscarinic
      receptors.
AB  - Interaction of the basic peptides dynorphin A and myelin basic protein with
      muscarinic receptors was investigated in rat heart and cerebral cortex using
      radioligand receptor binding assays. Results showed that these peptides inhibit
      the binding of the muscarinic ligand [3H]N-methylscopolamine at equilibrium and
      alter the kinetics of ligand dissociation in an allosteric fashion. The number of
      basic amino acid residues in the composition of dynorphin A is important in
      eliciting its allosteric interactions. Our data suggest that endogenous basic
      peptides play a role in regulating the conformation of muscarinic receptors.

PMID- 7506425
TI  - The through-and-through oromandibular defect: rationale for aggressive
      reconstruction.
AB  - Through-and-through oral cancer (T4+) involving contiguous mucosa, mandible, and
      skin is a devastating disease with poor prognosis and represents one of the most
      difficult reconstructive challenges in head and neck surgery. Thirty-eight
      patients underwent immediate microvascular reconstruction following surgical
      tumor ablation. The purpose of the present review was to assess the value of
      microvascular reconstruction in these essentially palliative reconstructive
      efforts. The iliac crest osteocutaneous flap was used in the majority of patients
      and was found to be ideal for the reconstruction of large bony and soft-tissue
      defects present in this group of patients. Other methods, including pectoralis
      major, forehead, and latissimus dorsi flaps, also were used in the soft-tissue
      reconstruction. The mean follow-up was 16 +/- 2 months, and the mean
      hospitalization was 43 +/- 22 days. The majority of patients succumbed to
      recurrent or related diseases, yet a few went on to survival despite the initial
      advanced stage of disease. A number of complications were observed. However, most
      patients developed normal or easily intelligible speech (65 percent), and most
      (78 percent) had their tracheostomies closed and sustained themselves on an oral
      soft diet (84 percent). Bony union was noted in the majority of patients (73
      percent). Although the prognosis in full-thickness oral carcinoma is grim, it
      appears that palliative surgery in these cases is well justified. The goals are
      to shorten the duration of hospitalization, reduce morbidity, and improve the
      remaining quality of life. Microvascular tissue transfer offers a means to
      achieve these goals in a single, reliable procedure. We feel that immediate one
      stage bone and soft-tissue reconstruction restores dignity and relieves suffering
      in this unfortunate group of individuals.

PMID- 7506426
TI  - An Arabidopsis thaliana lipoxygenase gene can be induced by pathogens, abscisic
      acid, and methyl jasmonate.
AB  - We isolated and characterized a 2.8-kb, full-length, Arabidopsis thaliana cDNA
      clone encoding a lipoxygenase. DNA sequence analysis showed that the deduced
      amino acid sequence of the Arabidopsis protein is 72 to 78% similar to that of
      legume seed lipoxygenases. DNA blot analysis indicated that Arabidopsis contains
      a single gene, LOX1, with appreciable homology to the cDNA clone. RNA blot
      analysis showed that the LOX1 gene is expressed in Arabidopsis leaves, roots,
      inflorescences, and young seedlings. LOX1 expression levels were highest in roots
      and young seedlings. In mature plants, LOX1 mRNA levels increased upon treatment
      with the stress-related hormones abscisic acid and methyl jasmonate and remained
      high for at least 96 h. Expression of the LOX1 gene was examined following
      infiltration of leaves with virulent (Psm ES4326) and avirulent (Pst MM1065)
      strains of Pseudomonas syringae. LOX1 mRNA levels were induced approximately 6
      fold by both virulent and avirulent strains; however, the response to avirulent
      strains was much more rapid. Infiltration of leaves with Pst MM1065 resulted in
      maximal induction within 12 h, whereas maximal induction by Psm ES4326 did not
      occur until 48 h. When a cloned avr gene, avrRpt2, was transferred to Psm ES4326,
      LOX1 mRNA accumulated in a pattern similar to that observed for the avirulent
      strain Pst MM1065.

PMID- 7506427
TI  - Complementary immunolocalization patterns of cell wall hydroxyproline-rich
      glycoproteins studied with the use of antibodies directed against different
      carbohydrate epitopes.
AB  - Antisera raised against the major hydroxyproline-rich glycoprotein (HRGP) in
      carrot (Daucus carota L.) taproot, extensin-1, and a minor HRGP, extensin-2, were
      characterized by western blot analysis, enzyme-linked immunosorbent assay, and
      periodate oxidation and found to be directed against carbohydrate epitopes shared
      by both glycoproteins. The anti-extensin-1 antibodies (gE1) target periodate
      sensitive epitopes and may recognize the terminal alpha-1,3-arabinoside of
      extensin-1. The anti-extensin-2 antibodies (gE2) recognize periodate-insensitive
      epitopes, possibly binding the reducing, internal beta-1,2-arabinosides on the
      carbohydrate side chains. Despite the cross-reactivity of these antibodies,
      immunolocalization studies of carrot taproot and green bean (Phaseolus vulgaris
      L.) leaf tissues reveal a spatial segregation of gE1- and gE2-labeling patterns.
      The gE1 antibodies bind only to the cellulose-rich region of the cell wall (J.P.
      Staehelin and L.A. Stafstrom [1988] Planta 174: 321-332), whereas gE2 labeling is
      restricted to the expanded middle lamella at three cell junctions. Periodate
      oxidation of nonosmicated, thin-sectioned tissue abolishes gE1 labeling but leads
      to labeling of the entire cell wall by gE2, presumably as a result of unmasking
      cryptic epitopes on extensin-1 in the cellulose layer. Purified extensin-2
      protein is more efficient than extensin-1 protein at agglutinating avirulent
      Pseudomonas strains lacking extracellular polysaccharide. Our results indicate
      that extensin-2 does not form a heterologous HRGP network with extensin-1 and
      that, in contrast to extensin-1, which appears to serve a structural role,
      extensin-2 could participate in passive defense responses against phytopathogenic
      bacteria.

PMID- 7506428
TI  - Engagement of the CD19 receptor on human B-lineage leukemia cells activates LCK
      tyrosine kinase and facilitates radiation-induced apoptosis.
AB  - As presently reported, both ionizing radiation and engagement of the CD19
      receptor are capable of inducing apoptosis in B-lineage acute lymphoblastic
      leukemia (ALL) cells. In both instances, activation of tyrosine kinases appears
      to be a proximal and mandatory step, since it can be prevented by the tyrosine
      kinase inhibitor genistein. This common biochemical signaling pathway involves
      the rapid activation of the Src family tyrosine kinase LCK (p56lck), which is
      physically associated with the CD19 receptor, and enhanced tyrosine
      phosphorylation of multiple substrates leading to stimulation of phosphoinositide
      turnover, and activation of protein kinase C. Importantly, engagement of the CD19
      receptor promoted radiation-induced apoptosis in radiation-resistant B-lineage
      ALL cells in a cell type-specific fashion. Our results prompt the hypothesis that
      clonogenic B-lineage ALL blasts with an inherent or acquired resistance to
      radiation could be radiosensitized in clinical settings using anti-CD19 MoAb B43
      or its homoconjugate as adjuncts.

PMID- 7506429
TI  - [Biochemistry of keratin proteins].

PMID- 7506430
TI  - [New small RNAs in eubacteria].

PMID- 7506431
TI  - [Trial and possibility of symbolization of techniques in molecular biology].

PMID- 7506432
TI  - Inhibition of prostacyclin-induced Ca2+ mobilization by phorbol esters in Ob1771
      preadipocytes.
AB  - In addition to cAMP production, a transient elevation of intracellular free Ca2+
      has been shown to take place in preadipose cells upon stimulation by
      carbaprostacyclin (cPGI2), both messengers acting in synergy to initiate adipose
      cell differentiation (Vassaux, G., Gaillard, D., Ailhaud, G., and Negrel, R.
      (1992) J. Biol. Chem.267, 11092-11097). Further studies reported herein show that
      this Ca2+ transient is i) elicited by the natural prostaglandin PGI2, ii)
      independent of the presence of extracellular Ca2+, suggesting a mobilization of
      Ca2+ from intracellular pools and ii) unaffected by cAMP elevating agents.
      Moreover, and in contrast to the InsP3-dependent Ca2+ signal evoked by PGF2
      alpha, that induced by PGI2 is fully abolished by pretreatment with phorbol
      esters (EC50: 1-5 nM). Furthermore, experiments designed to empty the Ca2+ pools,
      using PGI2 or PGF2 alpha as Ca2+ mobilizing agents as well as pretreatments with
      drugs, allow to conclude that PGI2 mobilizes Ca2+ from an InsP3 sensitive,
      ryanodine insensitive intracellular pool. Altogether, these results strongly
      suggest that PGI2 mobilizes Ca2+ from an intracellular store common to that
      affected by InsP3, by means of a mechanism which remains to be elucidated.

PMID- 7506433
TI  - Acquired megacolon is associated with alteration of vasoactive intestinal peptide
      levels and acetylcholinesterase activity.
AB  - Based upon previous morphologic studies, we hypothesized that the development of
      acquired megacolon was associated with abnormalities of enteric neurotransmitter
      concentrations and enzymatic activities. Specimens were obtained at surgery from
      patients with normal descending-sigmoid colon (n = 13) and patients with sigmoid
      megacolon (n = 6; defined by radiologic measurement). Radioimmunoassays were used
      to measure the non-adrenergic, non-cholinergic inhibitory neuropeptide,
      vasoactive intestinal peptide, and the non-adrenergic, non-cholinergic excitatory
      neuropeptide, substance P, while spectrophotometric assays were used to
      quantitate acetylcholinesterase activity and choline acetyltransferase activity.
      There were significantly decreased concentrations of vasoactive intestinal
      peptide and decreased acetylcholinesterase activity in muscularis externa from
      patients with acquired megacolon. In megacolon, vasoactive intestinal peptide
      containing nerve fibers appeared to be diminished in circular and longitudinal
      smooth muscle, and immunostaining of nerve cell bodies in the plexus submucosus
      externus appeared diminished. These results suggest the hypothesis that
      production of vasoactive intestinal peptide is altered allowing secondary colonic
      hypertrophy to develop from prolonged cholinergic nerve-mediated contractions of
      circular smooth muscle. As a corollary to this hypothesis, colonic dilatation
      might result from prolonged contraction of longitudinal smooth muscle.

PMID- 7506434
TI  - Somatostatin inhibits gastrin-induced histamine secretion and synthesis in the
      rat.
AB  - Somatostatin is a potent inhibitor of gastric acid secretion. However, the effect
      of somatostatin on gastric histamine secretion and synthesis has not been well
      understood, despite the fact that histamine plays a key role in the regulation of
      gastric acid secretion. This study was designed to determine the effect of
      somatostatin on gastric histamine mobilization and acid secretion in conscious
      rats. In conscious rats with a gastric fistula, a 4 h intravenous infusion of
      gastrin-17 I (1 nmol/kg/h) evoked a marked increase in fundic histidine
      decarboxylase activity (the sole histamine-forming enzyme) and reduced fundic
      histamine content with a concomitant increase in gastric acid secretion.
      Somatostatin-14 (10 nmol/kg/h) significantly inhibited gastrin-induced gastric
      acid secretion and fundic histidine decarboxylase activity and prevented a
      gastrin-induced decrease in fundic histamine content. In conscious rats with a
      vesical fistula, somatostatin-14 (10 nmol/kg/h) significantly inhibited the
      urinary histamine excretion induced by a gastrin-17 I (1 nmol/kg/h) infusion.
      These findings suggest that the inhibitory action of somatostatin on gastrin
      induced acid secretion is mediated by the inhibition of histamine mobilization.

PMID- 7506435
TI  - CGRP(8-37) and CGRP(32-37) contract the iris sphincter in the rabbit eye:
      antagonism by spantide and GR82334.
AB  - The effects of intracameral injections of CGRP(8-37) and CGRP(32-37) on pupil
      diameter and blood-aqueous barrier have been investigated in rabbits. The
      rabbits, which were pretreated with indomethacin and a muscarinic antagonist
      (biperiden), responded with miosis to both CGRP fragments. CGRP(8-37) was much
      more potent than CGRP(32-37) but one order of magnitude less potent than
      substance P. Nerve blockade with tetrodotoxin did not affect the response,
      indicating a direct effect on the iris sphincter muscle. Pre-treatment with the
      unselective tachykinin receptor antagonist spantide or the NK1 receptor selective
      antagonist GR82334 caused a rightward shift of the dose-response curves for both
      fragments, while the CCK receptor antagonist loxiglumide had no inhibitory
      effect. Neither of the fragments induced any marked leakage of Evans blue into
      the aqueous humor indicating that there was no agonistic interaction with CGRP
      receptors in the eye. We conclude that CGRP(8-37) and CGRP(32-37) are miotic
      agents in the rabbit eye, possibly by acting as neurokinin receptor agonists.

PMID- 7506436
TI  - Critique of R. Melnick's "An alternative hypothesis on the role of chemically
      induced protein droplet (alpha 2u-globulin) nephropathy in renal carcinogenesis".

PMID- 7506437
TI  - Critique does not validate assumptions in the model on alpha 2u-globulin and
      renal carcinogenesis.

PMID- 7506438
TI  - Effect of ifosfamide metabolites on sodium-dependent phosphate transport in a
      model of proximal tubular cells (LLC-PK1) in culture.
AB  - Ifosfamide (IF) is an alkylating cytostatic drug with urotoxic (hemorrhagic
      cystitis) and nephrotoxic side effects. Several cases of Fanconi syndrome in
      children following therapy with IF were reported. Little information is available
      concerning the pathomechanisms of transport inhibition by IF. We used a permanent
      renal epithelial cell line with proximal tubular characteristics (LLC-PK1) in
      order to investigate the effects of IF and some of its major metabolites (4-OH
      IF, chloracetaldehyde, and acrolein). LLC-PK1 cells were used in a confluent
      state. Sodium-dependent and sodium-independent fluxes of 32PO4 were determined by
      standard techniques. Activities of marker enzymes of apical and basolateral
      membranes, of mitochondria, and of endoplasmic reticulum were determined in cell
      homogenates. IF induces a moderate stimulation of PO4 transport. 4-OH-IF also has
      a stimulatory effect on transport at low concentrations (up to 200 mumol/l) and
      with short incubation (2h), while a 24-hour exposure of cells to 100 mumol/l of 4
      OH-IF has an inhibitory effect of PO4 transport. Concentrations of 4-OH-IF which
      inhibit transport also reduce the activity of Na(+)-K(+)-ATPase.
      Chloracetaldehyde, like 4-OH-IF, induces a biphasic response of PO4 transport
      with stimulation in the low concentration range (up to 75 mumol/l) and inhibition
      at higher concentrations. Chloracetaldehyde reduces the activity of succinate
      cytochrome c oxidoreductase, suggesting that a defect in ATP generation might
      play a role in the pathogenesis of Fanconi syndrome induced by IF. Acrolein
      strongly damages monolayers and reduces sodium-dependent transport of PO4 to very
      low levels at 150 mumol/l. It reduces the activities of both Na(+)-K+ ATPase and
      succinate-cytochrome c oxidoreductase. Acrolein also is the only metabolite with
      a moderate effect on alkaline phosphatase. We conclude that sodium-dependent
      transport of PO4 is highly sensitive to IF metabolites. In addition to direct
      toxic effects of IF metabolites on transport proteins within the apical plasma
      membrane, damage to mitochondrial enzymes and to Na(+)-K+ ATPase which generates
      the electrochemical gradients for secondary active PO4 transport may play an
      important role in the pathogenesis of Fanconi syndrome induced by IF.

PMID- 7506439
TI  - Selective release of apical membrane enzymes from cultured renal epithelia by
      phosphatidylinositol-specific phospholipase C.
AB  - Membrane proteins can be attached to the plasma membrane in several ways.
      Recently, a mechanism has been described, by which a number of cell surface
      proteins are anchored to the exoplasmic side of the plasma membrane by covalent
      linkage to glycosyl-phosphatidylinositol (GPI). The growth properties of renal
      epithelial cells in tissue culture enable free access to apical cell surface and
      brush border membrane proteins. To study the nature of membrane anchoring of
      apical plasma membrane enzymes in cultured renal epithelial cells, confluent LLC
      PK1, OK, NRK, and MDCK epithelia were treated in tissue culture dishes with
      bacterial phosphatidylinositol-specific phospholipase C (PI-PLC), and the PI-PLC
      specific release into the tissue culture medium of the apical membrane enzymes
      alkaline phosphatase (AP), gamma-glutamyl transpeptidase, leucine aminopeptidase,
      trehalase, and maltase was determined. Of the five enzymes tested, AP and
      trehalase, already described as GPI-anchored membrane proteins, were specifically
      released by PI-PLC from intact cell monolayers. Of the four cell lines
      investigated, LLC-PK1 cells express AP and trehalase which were released by PI
      PLC. In OK cells, which lack AP activity, only trehalase was found to have PI-PLC
      releaseable enzyme activity. MDCK cells, on the other hand, express AP activity,
      releaseable by PI-PLC, but no trehalase activity. In studies on the time course
      of synthesis and reinsertion of AP into the apical membrane of LLC-PK1 cells
      after removal by PI-PLC, a 60% recovery of AP activity was obtained only after 7
      days. Analysis of protein release by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of culture supernatants after surface labeling with biotin and
      subsequent Western blotting with streptavidin revealed four protein bands at
      approximately 130, 90, 30, and 20 kD in LLC-PK1 cells and five GPI-anchored
      proteins at 110, 85, 65, 40, and 26 kD in OK cultures. The finding of a PI-PLC
      specific release of apical membrane enzymes from renal tubular cell lines of
      different species (pig, opossum, rat, and dog) and of different nephron origin
      indicates a high conservation of the GPI anchor of renal brush border membrane
      proteins and further proves the high degree of differentiation retained by the
      cell lines in tissue culture. In addition, this method may provide a possible
      tool for isolating GPI-anchored apical membrane proteins from intact epithelial
      monolayer cultures.

PMID- 7506440
TI  - Substrate uptake and utilization by the kidney of fed and starved rats in vivo.
AB  - In order to obtain information (1) on the quantitative contribution of various
      circulating substrates to renal metabolism and (2) on the relative importance of
      net luminal and basolateral transport for substrate uptake, we have precisely
      quantified the renal blood flow, the urinary flow, and the rates of substrate
      handling by the kidney of anesthetized fed and 72-hour-starved rats. For this,
      the concentration of twelve metabolites were simultaneously measured in arterial
      and venous whole blood and plasma as well as in urine of each rat thanks to the
      use of microassays based on enzymatic cycling. In fed rats, the main potential
      energy sources were glucose and lactate followed by fatty acids, ketone bodies,
      citrate and glycerol. Starvation caused a large increase in renal uptake and
      metabolism of fatty acids, ketone bodies, glutamine and glycerol, and a large
      inhibition of lactate utilization. The net peritubular uptake of acetoacetate,
      citrate, glycerol and free fatty acids demonstrated in both nutritional states
      was increased by starvation only for glycerol and free fatty acids; net
      peritubular efflux of both beta-hydroxybutyrate and ammonium ions was stimulated
      whereas that of glutamine was converted into net peritubular uptake by
      starvation.

PMID- 7506441
TI  - The direct renal tubular effect of angiotensin II in chicken.
AB  - Taking advantage of the particular renal vascular arrangement in cocks,
      angiotensin II was injected (0.12-0.96 microgram/min) into the portal system of
      one kidney in order to increase the angiotensin II concentration in the
      physiological nanomolar range at the level of the renal tubules. Angiotensin II
      induced an increase in blood pressure of 5% and a bilateral rise in glomerular
      filtration rate and effective renal plasma flow of 28 and 22%, respectively. The
      urine volume increased five times on the infused side and three times on the
      control side. The Na+ excretion increased 14 times on the infused side and only
      seven times on the control side. During angiotensin infusion, the fractional
      water excretion was 4.9% on the infused side and 2.9% on the control side versus
      1.1 and 1.2% during the control period. For the fractional Na+ excretion, the
      respective values were 2 and 1.2% versus 0.2 and 0.2% during the control period.
      The differences between the two kidneys demonstrate the direct tubular action of
      angiotensin II, inhibiting the tubular Na+ and water reabsorption at
      physiological nanomolar concentrations. Angiotensin seems thus to play an
      important intrarenal role.

PMID- 7506442
TI  - Liver regeneration in rats after complete and partial occlusion of the portal
      blood influx.
AB  - The role of portal blood influx in liver regeneration was studied in rats.
      Partial hepatectomy with removal of 45% of the liver mass was performed after end
      to-side portacaval shunt (PCS) leading to complete diversion of portal blood from
      the liver, or after side-to-side PCS causing partial portal blood deprivation.
      Liver resection was limited to 45% to avoid the high mortality rate in rats with
      vascular anastomoses and 70% hepatectomy, but it did not change the pattern of
      liver regeneration. The total RNA and DNA content, the rate of DNA synthesis and
      the number of hepatocyte mitoses in regenerating liver were measured in
      comparison to sham-operated controls. Complete occlusion of the portal blood
      influx did not block hepatoproliferative response, but caused a significant
      decrease and delay of regeneration. Partial preservation of portal flow in rats
      with side-to-side PCS markedly improved liver regeneration in comparison to end
      to-side PCS, but the process was slower than in the control group.

PMID- 7506443
TI  - Effects of guanine nucleotides on bombesin-stimulated signal transduction in rat
      pancreatic acinar cells.
AB  - To study the role of guanine nucleotide binding proteins (G proteins) in bombesin
      receptor signal transduction, we investigated the effects of guanine nucleotide
      analogues and of the G protein activator NaF on bombesin-induced amylase release,
      inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) production and release of
      intracellular Ca2+ in rat pancreatic acini. In digitonin-permeabilized acini,
      guanosine 5'-[gamma-thio]triphosphate (GTP gamma S), a well-known activator of G
      proteins, potentiated bombesin-induced Ins(1,4,5)P3 production and increased
      amylase release at low bombesin concentrations (< 10 nM). By contrast, GTP gamma
      S decreased bombesin-stimulated amylase release at high bombesin concentrations
      (> 10 nM). Fluoride (10 mM), another G protein activator, had similar effects to
      GTP gamma S on amylase release. However, unlike GTP gamma S it had no effect on
      Ins(1,4,5)P3 production and release of intracellular Ca2+ induced by high
      bombesin concentrations. GDP and its analogues, such as 2'-desoxyguanosine 5'
      diphosphate (dGDP) or guanosine 5'-[beta-thio]diphosphate (GDP beta S), inhibit
      activation of G proteins. GDP and dGDP both inhibited amylase release and
      Ins(1,4,5)P3 production at all bombesin concentrations tested. In contrast, GDP
      beta S mimicked the effects of GTP gamma S on bombesin-stimulated amylase release
      and Ins(1,4,5)P3 accumulation. In conclusion, we suggest that bombesin receptor
      mediated signal transduction involves G proteins in pancreatic acini. The
      correlation between inhibition of maximum-stimulated enzyme secretion and further
      increase in Ins(1,4,5)P3 production in response to GTP gamma S at high bombesin
      concentrations suggests that overstimulation of phospholipase C inhibits amylase
      release. The discrepant effects of GDP and of GDP beta S on phospholipase C
      activity and amylase release might be due to the ability of GDP beta S, but not
      of GDP to activate G proteins persistently after phosphorylation by G protein
      associated GDP kinases.

PMID- 7506444
TI  - Augmentation of hepatocyte proliferation by immunosuppressant pretherapy is
      associated with up-regulation of malondialdehyde production.
AB  - We studied the relationship between augmentation of liver regeneration with
      immunosuppressants and malondialdehyde (MDA, an end-product of lipid peroxides)
      production. MDA was determined using the thiobarbituric acid reaction. Rats
      underwent a 4-day treatment of FK506 (FK, 1 mg/kg per day), cyclosporine (Cs, 10
      mg/kg) or azathioprine (AZA, 1 mg/kg) by gavage prior to 70% hepatectomy. They
      were then divided into four groups: (1) controls (vehicle-treated); (2) FK; (3)
      Cs; (4) AZA. MDA levels, uptake of BrdU (5-bromo-2-deoxyuridine) in the liver and
      serum biochemistry were investigated 24 h after hepatectomy. Immunosuppressant
      pretherapy significantly stimulated BrdU uptake by hepatocytes, in association
      with increased MDA production, while there were no differences in serum liver
      injury parameters among the groups given or not given immunosuppressants. The
      implications of the rising MDA values during liver regeneration are discussed
      with respect to immunosuppression and a measure of lipid peroxidation. Additional
      study indicated that one immunodepressant pretreatment (24 h prior to
      hepatectomy) was effective for up-regulation of liver regeneration.

PMID- 7506445
TI  - [Prevalence of HBsAg, anti-HBc and anti-HCV in blood donor candidates at the
      Campinas hemocenter].
AB  - Among 29833 donors evaluated we have found a prevalence of 1.52% for HBsAg and
      11% for anti-HBc. The co-positivity anti-HBc/anti-HBs in 2783 donors HBsAg
      negative/anti-HBc positive was 81.9%. The prevalence for HBsAg is low among
      Campinas donors, while anti-HBc presents high prevalence when compared to that of
      other countries. The anti-HCV detection in blood donors of Campinas has shown a
      positivity of 2.6% which is much higher than that of USA and Europe. About 36% of
      the anti-HCV positive donors are anti-HBc reagent, leading to the conclusion that
      these two "viruses" infect simultaneous or sequentially Brazilian blood donors.

PMID- 7506446
TI  - [Post-transfusional hepatitis in the city of Campinas, SP, Brazil. I. Incidence,
      etiological agents and clinico-epidemiological aspects of hepatitis C].
AB  - We have followed up 111 transfusion receptors in the ambulatory, for at least 180
      days, in order to evaluate the occurrence of post-transfusional hepatitis and the
      etiological agents involved in the disease in the city of Campinas, state of Sao
      Paulo, Brazil. At the end of the study we have diagnosed this hepatitis in 18
      (16.2%) subjects. Out of these 18 subjects, 16 (89%) were caused by hepatitis C
      virus, 1 (5.5%) caused by hepatitis B virus and 1 (5.5%) with undetermined
      etiology, 15 months after transfusion. The average incubation period of HCV was
      71 days and 23% of the HCV positive receptors remained with increased AST/ALT for
      more than 6 months. Late serum conversion was observed for anti-HCV in 71.4% of
      the subjects, averaging 135 days after the transfusion. An ALT dosage and anti
      HCV determination, 3 and 6 months after transfusion would diagnose, respectively,
      71 and 93% of the cases which developed post-transfusional HCV.

PMID- 7506447
TI  - [Post-transfusional hepatitis in the city of Campinas, SP, Brazil. II. Presence
      of anti-HBc and anti-HCV antibodies in blood donor candidates and occurrence of
      post-transfusional hepatitis C in recipients of blood or derivates].
AB  - We have analysed anti-HBc and anti-HCV antibodies in serum samples from 799
      donors which had their blood or derivates transfused to 111 recipients. Anti-HBc
      and anti-HCV were reactive in respectively 9 and 2.1% of the donors tested. We
      have observed that among the 111 recipients, 44 had received at least one
      positive anti-HBc unit and 67 had been transfused only with negative anti-HBc,
      units. The risk of developing hepatitis C virus was 4.5 times higher for the
      recipients who received at least one positive anti-HBc unit. If the test for anti
      HBc had been made for the blood donors in the serological screening, about 56% of
      the HCV cases in the recipients could have been avoided. The population of
      recipients who received at least one reacting unit of anti-HCV, presented a risk
      29 times higher of developing this hepatitis, as compared to the transfused
      recipients with all anti-HCV negative units. Testing blood from donors for anti
      HCV would avoid 79% of the post-transfusional HCV cases. Brazilian candidates to
      blood donors seem to be carriers either simultaneously or sequentially to
      hepatitis virus B and C, since 44.4% of the positive anti-HCV were also positive
      for anti-HBc. Testing for anti-HBc and anti-HCV in blood screening must be
      indicated in order to prevent post-transfusional hepatitis transmission in our
      community.

PMID- 7506448
TI  - The treatment of chronic extremity pain in failed lumbar surgery: the role of
      lumbar sympathectomy.

PMID- 7506449
TI  - Chronic treatment with fluvoxamine increases extracellular serotonin in frontal
      cortex but not in raphe nuclei.

PMID- 7506450
TI  - Differences in rejection grading after simultaneous pancreas and kidney
      transplantation in pigs.
AB  - Clinical observations suggest that recipients of multiorgan transplants from the
      same donor can have disparate immunological reactions to each organ. We studied
      this phenomenon in 36 diabetic (streptozotocin-induced), bilaterally
      nephrectomized immunosuppressed (cyclosporine, azathioprine, prednisone) pig
      recipients of simultaneous (same donor) pancreas (bladder drained) and kidney
      allografts by grading the histological intensity of rejection in biopsies of each
      organ at defined intervals posttransplant. Graft function was monitored by plasma
      glucose (PG) and urine amylase (UA) for the pancreas and serum creatinine (Cr)
      for the kidney. Interstitial rejection was graded as absent, mild, moderate, and
      severe in, respectively, 8%, 25%, 42%, and 5% of pancreas vs. 4%, 12%, 27%, and
      50% of kidney biopsies at 1 week; and 0%, 43%, 29%, and 29% of pancreases vs.
      10%, 0%, 30%, and 60% of kidneys at two weeks. Although the distribution of
      grades was similar in the two organs (P > 0.1), the grade of rejection for each
      pair at 1 week (n = 24) was discordant in 75% (41% differed by one and 35% by >
      or = 2 grades) and at 2 weeks (n = 7) in 57% (29% by 1 and 29% by > or = 2
      grades). The inability to use the severity of interstitial rejection in one organ
      to predict the findings in the other is exemplified by the fact that for the two
      pancreases without interstitial rejection at one week, the corresponding kidney
      showed moderate or severe rejection, and for the 1 kidney without rejection the
      corresponding pancreas showed moderate rejection. Vascular rejection grades
      (absent, mild, moderate, severe) also showed a similar distribution for the
      pancreas (57%, 30%, 9%, 4%) vs. kidney (56%, 30%, 0%, 13%) at 1 week, and at 2
      weeks (57%, 29%, 0%, and 14% for the pancreas vs. 78%, 11%, 0%, and 11% for the
      kidney) (P > or = 0.64). However, the grading of vascular rejection in organ
      pairs was dyssynchronous in 51% at 1 week (n = 22) and 29% at 2 weeks (n = 7). No
      vascular rejection in the pancreas with rejection in the kidney was seen in 5
      pairs at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kidney
      with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at
      2 weeks (29%).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7506451
TI  - Non-A, non-B hepatitis and elevated serum aminotransferases in renal transplant
      patients. Correlation with hepatitis C infection.
AB  - One hundred renal transplant recipients were studied for antibodies to hepatitis
      C virus (HCV), and to HCV RNA in serum by reverse transcription+nested polymerase
      chain reaction (RT-PCR). Presence of antibody to HCV confirmed by recombinant
      immunoblot assay II was considered evidence of HCV infection, and detection of
      HCV RNA by RT-PCR was considered evidence for active viremia. On pretransplant
      sera, 18 patients were RT-PCR positive and an additional 3 had antibody evidence
      of HCV infection. At 1-year follow-up, all of these patients were RT-PCR positive
      and an additional 7 patients became RT-PCR positive. Clinical diagnosis of non-A,
      non-B hepatitis underestimated the prevalence of HCV infection (5/28 cases, 18%).
      Serum alanine aminotransferase (ALT) elevations were neither sensitive nor
      specific. An isolated pretransplant ALT elevation predicted a 52% chance of being
      RT-PCR positive for HCV. An ALT elevation greater than 2 months after transplant
      predicted a 45% chance of HCV positivity; however, 18% of patients who never had
      any ALT abnormality were also HCV positive. Sixty-eight patients had an early
      postoperative rise in ALT, but there was no correlation with HCV status. After an
      average follow-up of over 4 years, 3/28 HCV-positive patients developed
      cirrhosis. HCV infection in the renal transplant population is common and
      underdiagnosed by clinical and biochemical parameters. HCV appears not to cause
      aggressive liver disease in the early posttransplant period, but longer follow-up
      is needed to define the natural history of HCV in the renal transplant
      population.

PMID- 7506452
TI  - FK506 versus cyclosporine as primary immunosuppressive agent for orthotopic liver
      allograft recipients. Histologic and immunopathologic observations.
AB  - We investigated possible explanations for the common occurrence of perivenular
      lesions in liver allografts of patients on FK506 within a few weeks to several
      months after OLT. Hematoxylin and eosin-stained sections of pre- and
      postperfusion biopsy specimens and day 7 post-transplant protocol biopsy
      specimens from 31 patients, randomly assigned to either FK506 or CsA as primary
      immunosuppressive agent, were reviewed, and immunohistochemical stains for HLA-DR
      antigen and S-100 protein were performed by the avidin-biotin peroxidase complex
      method. The histologic features of cellular rejection in the portal tracts of day
      7 posttransplant allograft biopsy specimens from patients on FK506 were milder
      than those from patients on CsA. Immunohistochemical stains for HLA-DR showed
      intense positivity in a variety of cell types in day 7 posttransplant specimens
      from both groups, including sinusoidal-lining cells, bile duct epithelial cells,
      vascular endothelial cells, inflammatory cells, and occasional injured
      hepatocytes. Although diffuse lobular staining was seen in the majority of cases
      in both groups, either with or without rejection, liver biopsy specimens from
      patients on FK506 showed concentration of positively stained cells in perivenular
      regions more often, and at a lower overall histologic grade of rejection, than
      specimens from patients on CsA. There were no differences in the number and
      distribution of S-100 protein-positive dendritic APC between biopsy specimens
      from FK506 versus CsA-treated patients, or between specimens with and without
      cellular rejection in either group. It is suggested that the development of
      perivenular injury, which is seen frequently in allograft biopsy specimens from
      patients on FK506 obtained at various intervals after transplantation, may be
      related to drug toxicity rather than to the process of allograft rejection.

PMID- 7506453
TI  - Frozen section evaluation of donor livers before transplantation.
AB  - Frozen section examination was performed on 385 donor livers before
      transplantation. Exclusion criteria were applied to the donor livers examined to
      exclude potentially dysfunctional livers. The exclusion criteria included the
      following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic
      portal inflammation, prominent periductular fibrosis, granulomatous inflammation,
      bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined
      were excluded before transplantation. The following histologic features were
      present in the excluded livers: severe steatosis (22), ischemic necrosis (2),
      portal inflammation (1), and periductular fibrosis (2). Steatosis was present in
      51 of the 385 (13.25%) organs examined, including 22 of the donor organs excluded
      before transplantation. Twenty-nine livers with mild to moderate steatosis were
      implanted into size and blood type-matched recipients. Indicators of allograft
      function (prothrombin time and bilirubin) and damage (aspartate aminotransferase
      and alanine aminotransferase) were measured daily for the first 10 days after
      transplant. There was no statistically significant difference between the group
      of nonfat livers and donor livers containing mild steatosis. Statistically
      significant higher posttransplant serum alanine aminotransferase and prothrombin
      time levels were present in the patients with livers implanted with mild versus
      moderate steatosis. The 1-year survival rate for patients receiving fatty versus
      nonfatty donor livers was not statistically different (Kaplan-Meier, P = 0.592).
      No significant differences were found in the clinical and laboratory
      characteristics of donors whose organs were implanted compared with the clinical
      and laboratory characteristics of donors whose organs were excluded. The primary
      nonfunction rate after applying the exclusion criteria was 1.4%, which is a
      significant decrease compared with our primary nonfunction rate of 8.5% before
      using frozen section examination. Frozen section examination is useful in
      excluding donor organs which may become dysfunctional after transplantation.

PMID- 7506454
TI  - Effects of FK506 and cyclosporine on dynamic insulin secretion from isolated dog
      pancreatic islets.
AB  - Pancreatic islet transplantation may be the most ideal treatment for patients
      with insulin-dependent diabetes mellitus. However, immunosuppressive agents such
      as cyclosporine A(CsA) and FK506, used for these transplanted patients have been
      reported to cause glucose intolerance. In the present study, we have compared the
      effects of CsA and FK506 on glucose-stimulated insulin release from the isolated
      dog pancreatic islets, which have been maintained in culture for 3 days after
      isolation. The isolated dog pancreatic islets, pretreated for 24 hr with either
      CsA or FK506 (1, 10, and 100 nM), were perifused with 16.7 mM glucose.
      Pretreatment with both drugs suppressed glucose-stimulated insulin secretion in a
      dose-dependent fashion. CsA (100 nM), which is a therapeutically relevant
      concentration, significantly suppressed both the first and second phases of
      glucose-stimulated insulin release compared with 100 nM FK506. These findings
      suggest that, with a therapeutically relevant concentration, FK506 may be less
      toxic than CsA against pancreatic islets in patients with organ or cell
      transplantation.

PMID- 7506455
TI  - Human islet transplantation--is blood group compatibility important?

PMID- 7506456
TI  - Effective prevention of ischemic injury of the dearterialized canine liver by
      FK506 pretreatment.

PMID- 7506457
TI  - Intrathymic transplantation of allogeneic nonimmunogenic perinatal islet tissue
      does not induce donor-specific tolerance.

PMID- 7506458
TI  - Enhancement of allograft survival by single intraoperative donor-specific blood
      transfusion combined with FK506.

PMID- 7506459
TI  - FK506 and pregnancy in liver transplant patients.

PMID- 7506460
TI  - Successful pregnancy in a patient after liver transplantation maintained on FK
      506.

PMID- 7506461
TI  - Reversal of neutropenia with granulocyte colony-stimulating factor without
      precipitating liver allograft rejection.

PMID- 7506462
TI  - Immunohistochemical determination of age related proliferation rates in normal
      and benign hyperplastic human prostates.
AB  - To study whether benign prostatic growth in aging men correlates with an increase
      in proliferation, proliferation rates were determined immunohistochemically using
      the antibody Ki-67 in 20 benign hyperplastic prostates (BPH) and in four normal
      prostates (NPR). There was no significant correlation between age and
      proliferation rate in epithelium or stroma in BPH. In addition, no significant
      correlation between prostate weight and proliferation rate could be demonstrated
      in either compartment. In NPR the proliferation rate in epithelium and stroma was
      9 times and 37 times lower, respectively, than in BPH. Obviously the induction of
      BPH from NPR may be associated with a distinct increase in proliferation. The
      further increase in BPH volume, however, is not correlated with a further
      increase in proliferation rate.

PMID- 7506463
TI  - Role of intracellular Ca2+ stores in smooth muscle contractions of the guinea pig
      vas deferens.
AB  - Guinea pig vas deferens was used as an animal model for alpha-1 adrenoceptor
      (alpha 1-receptor) mediated contractions in human hyperplastic prostatic tissue.
      The selective alpha 1-receptor agonist, phenylephrine (PE), induced fully
      reversible, dose-dependent contractions antagonized by increasing concentrations
      of the alpha 1-receptor blockers prazosin (1-100 nM) and YM 617 (0.1-10 nM).
      Removal of extracellular Ca2+ reduced PE-evoked contractions in a time-dependent
      manner. Nifedipine (1-1000 nM), a blocker of voltage-dependent L-type Ca2+
      channels (VDCC), inhibited the PE-induced response by up to 65%. Removal of
      extracellular Ca2+ abolished the alpha 1-agonist reactivity in a time-dependent
      fashion. To elucidate the participation of intracellular Ca2+ stores in alpha 1
      receptor-mediated contractions, the tissue was pretreated with ryanodine (10
      microM) or thapsigargin (0.1 microM), established inhibitors of Ca2+ release from
      intracellular pools. Both substances reduced the PE contractions by up to 80%.
      Nifedipine suppressed the remaining contractions completely. This provides
      evidence that Ca2+ influx through VDCC and Ca2+ release from intracellular stores
      contribute to alpha 1-receptor-mediated contractions in the guinea pig vas
      deferens and may be important in obstructive benign prostatic hyperplasia.

PMID- 7506464
TI  - E-cadherin: a marker for differentiation and invasiveness in prostatic carcinoma.
AB  - Considerable controversy exists concerning the value of histomorphological data
      in the assessment of the malignant potential of prostatic carcinomas. We
      investigated the expression pattern of E-cadherin in human prostate at the
      translational level. E-cadherin is a specific epithelial cell-cell adhesion
      molecule which has previously been found to be expressed in well-differentiated
      non-invasive carcinoma cell lines but is lost in many poorly differentiated
      invasive cell lines. The E-cadherin expression pattern in the prostate samples
      was correlated with histopathological findings in the same specimens. We found
      strong E-cadherin expression in normal prostate and benign prostatic hyperplasia.
      A decrease in or loss of E-cadherin was seen in 13 of 14 locally advanced and in
      8 of 9 poorly differentiated prostatic carcinomas. We conclude that
      downregulation of E-cadherin expression plays a role in prostate carcinogenesis
      and invasiveness.

PMID- 7506465
TI  - [Inhibitors of plasmin-like enzymes and autofibronectin in the treatment of
      corneal epithelial defects].
AB  - Effects of instillations of proteinase inhibitors and autologous fibronectin on
      the course of regeneration processes in corneal epithelial defects were studied
      in patients after perforating and lamellar keratoplasty, cataract extraction,
      trabecul- and vitrectomy. Proteinase inhibitors contrykal or gordox were
      administered to these patients to neutralize increased activity of lacrimal
      plasmin-like enzymes which was 899.3 +/- 80.8 rel. U on day 1 of observation vs.
      50.72 +/- 7.73 in normal subjects. Contrykal (gordox) helped significantly reduce
      these enzymes activities in patients with corneal epithelial defects in
      comparison with the control group as soon as during the first days of the
      observation. Combined use of contrykal (gordox) and autologous fibronectin helped
      attain complete epithelialization in all the patients in 12.3 +/- 1.7 days (47.9
      +/- 6.3 days in controls).

PMID- 7506466
TI  - [Pilot project smoke-free workplace].
AB  - In 1991 SAN had acquired wide experience with firms which had introduced rules
      about smoking, governing where and when smoking is permitted at the workplace. A
      dossier was produced, based on this expertise, with the title: "Smoke-free
      Workplaces". A pilot project, taking Zurich as a model, was intended to
      demonstrate how health-promoting measures could be successfully put into effect
      in the context of smoking. The results of experimentation with six different,
      interlocking measures were collated, and evaluated with a view to their
      implementation throughout the whole of Switzerland. The basic components covered
      the three areas of Information, Raising Awareness, and Motivation, and focussed
      particularly on the following six points: Information materials; text/cartoons
      for internal company PR use; bids to wean people off smoking; the "5-day
      campaign" (a communication game, 5 min. a day); an information event raising the
      interest of the personnel on to a wide range of possibilities: Information,
      experience the reactions of your body on tobacco-smoke, expositions, opinion
      walls. And sixth: advice on strategy for employers and personnel managers.

PMID- 7506467
TI  - Interaction between tachykinins and CGRP in human skin.
AB  - Substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP)
      coexist in nerve fibres in the skin. CGRP causes erythema upon intracutaneous
      injection. The erythema is independent of axon reflexes and release of mast cell
      histamine. SP is known to produce a flare reaction that is dependent on axon
      reflexes and release of mast cell histamine. The flare reaction to NKA is known
      to depend predominantly on axon reflexes. The purpose of the present study was to
      investigate possible cooperation between SP and CGRP. SP was found to shorten the
      duration of the reddening induced by CGRP, injected concomitantly. NKA did not
      shorten the duration of the CGRP response. Local elimination of mast cells in the
      skin by treatment with compound 48/80 had the effect that SP lost its ability to
      shorten CGRP-evoked erythema. These observations support the suggestion that an
      SP-evoked release of proteolytic enzymes from mast cells could lead to
      accelerated degradation of CGRP.

PMID- 7506468
TI  - Evidence of increased keratinocyte proliferation in air-liquid interface cultures
      of non-bullous congenital ichthyosiform erythroderma.
AB  - Modern pharmacological and dermatological research requires the use of
      appropriate in vitro models which permit a faithful reproduction of various
      aspects of the in situ situation. The air-exposed culture of keratinocytes on
      dead de-epidermized dermis is one of the best models of in vitro epidermal
      differentiation known at the moment. In this study, we verified the model's
      validity for the reproduction of a hyperproliferative genodermatosis: non-bullous
      congenital ichthyosiform erythroderma. We used subcultured epidermal
      keratinocytes originating from normal and ichthyotic patients. Light and electron
      microscopy of pathological cultures disclosed, on day 14, a terminally
      differentiated epidermis with a marked granular layer and hyperkeratosis which,
      however, was not dramatically different from the normal controls. On day 25, the
      normal cultures displayed an even more pronounced hyperkeratosis and
      hypergranulosis, whereas the reconstructed epidermis of pathological origin
      presented a considerable reduction of the viable non-keratinized compartment and
      a focal parakeratosis. Indirect immunofluorescence revealed the expression of
      several differentiation markers which were not observed in the immersed culture
      models (e.g. the desmosome- and differentiation-related antigens KM48 and G36
      19). Abundant keratohyalin granules were stained with AKH1 antibody and observed
      even in the deep epidermal layers, but no profilaggrin-filaggrin conversion could
      be detected biochemically.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506469
TI  - Solid basal cell epithelioma (BCE) possibly originates from the outer root sheath
      of the hair follicle.
AB  - The presence and distribution of several cytokeratins (CKs) in 20 solid basal
      cell epitheliomas (BCEs) were investigated and compared with the pattern of CKs
      in normal epidermis, perilesional skin and in the outer root sheath (ORS) of the
      human hair follicle. Tissue samples were stained with monoclonal antibodies
      (MoAbs) against human CKs, using the APAAP technique. Additionally, CK profiles
      were assessed by gel electrophoresis and immunoblot technique. Cells of BCE and
      ORS were positively stained with the MoAb KL1, whereas the basal layer of normal
      epidermis remained negative. Six out of 20 BCEs were partially stained with the
      MoAb RPN1165, which also stained the lower ORS, but not the epidermal basal
      layer. Using SDS-PAGE and immunoblot, the CK profiles of BCE and ORS were almost
      identical, showing the presence of CKs 5, 6, 14, 16 and 17; the CK pattern of
      normal epidermis, however, showed the presence of CKs 1, 5, 10 and 14.
      Perilesional skin (< 5 mm) showed keratin changes similar to the BCE pattern; the
      basal layer was stained with the MoAb KL1 and the suprabasal layer was negative
      to MoAb CK1, in contrast to normal epidermis. Keratin analysis revealed a CK
      pattern of perilesional skin different from that of normal epidermis (CKs 1, 5,
      6, 10, 14, 16 and 17). Our immunohistochemical and biochemical investigations
      underline the possible role of the lower ORS as a cellular pool for the
      generation of BCE.

PMID- 7506470
TI  - Effects of octreotide on insulin-like growth factor I and metabolic indices in
      growth hormone-treated growth hormone-deficient patients.
AB  - Animals studies have demonstrated that in addition to inhibiting growth hormone
      (GH) secretion octreotide inhibits in a direct manner hepatic or peripheral
      insulin-like growth factor I (IGF-I) generation. To test this hypothesis in
      humans we studied ten GH-deficient patients with frequent blood sampling during
      38 h on two occasions. Regular GH therapy was discontinued 72 h prior to each
      study period. At the start of each study a subcutaneous (sc) injection of GH (3
      IU/m2) was given (at 18.00 h). In a single-blinded crossover design, patients
      received a continuous sc infusion of either octreotide (200 micrograms/24 h) or
      placebo (saline). The pharmacokinetics of GH were similar on the two occasions.
      The area under the curve +/- SEM of serum GH was 142.5 +/- 53.6 micrograms.l-1 x
      h-1 (octreotide) and 144.8 +/- 41.8 micrograms.l-1 x h-1 (placebo), (p = 0.73);
      Cmax (microgram/l) was 12.5 +/- 1.47 (octreotide) and 12.8 +/- 1.42 (placebo) (p
      = 0.83), and Tmax (h) was 6.1 +/- 0.97 (octreotide) and 5.2 +/- 0.65 (placebo) (p
      = 0.49). Growth hormone administration was associated with an increase in serum
      IGF-I (microgram/l), which was identical during the two studies, from 85.3 +/-
      19.4 to 174.25 +/- 30.3 for octreotide and from 97.0 +/- 26.4 to 158.8 +/- 28.2
      for placebo. Mean IGF-I levels (microgram/l) were 138.2 +/- 25.1 (octreotide) and
      134.5 +/- 28.6 (placebo) (p = 0.78). Similarly, the increase in IGF binding
      protein 3 (IGFBP-3) levels was identical. Mean IGFBP-3 levels (microgram/l) were
      2303 +/- 323 (octreotide) and 2200 +/- 361 (placebo) (p = 0.25).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7506471
TI  - Insulin-like growth factors and their binding proteins in plasma and milk after
      growth hormone-stimulated galactopoiesis in normally lactating women.
AB  - We performed a double-blind randomized placebo-controlled trial of recombinant
      human growth hormone (hGH) in normally lactating women (N = 8 per group) to
      investigate the endocrine mode of action of the galactopoietic effect of this
      hormone. Insulin-like growth factors I (IGF-I) and II (IGF-II) and their binding
      proteins (IGFBP-1, IGFBP-2 and IGFBP-3) were measured by radioimmunoassay in
      plasma and milk samples collected throughout the study. All assays were validated
      for human plasma and milk. Human GH treatment (0.1 IU.kg-1 body wt.day-1 for 7
      days) increased plasma concentrations of IGF-I from 22.1 +/- 1.3 nmol/l (mean +/-
      SEM) to 59.7 +/- 2.5 nmol/l (p < 0.01). At the end of the study the increase in
      plasma IGF-I correlated significantly with the increase in milk volume (r = 0.67,
      p < 0.005, N = 16). The IGF-I levels were considerably lower in milk, with 0.14
      +/- 0.03 nmol/l before and 0.31 +/- 0.04 nmol/l after hGH treatment. The increase
      in milk IGF-I levels (134.0 +/- 14.5%) with hGH treatment was significant (p <
      0.01) and plasma and milk IGF-I concentrations correlated significantly when
      considering all samples of the study (r = 0.45, p < 0.001, N = 56). The
      concentrations of IGF-II were not changed significantly with hGH treatment in
      plasma (52.5 +/- 2.5 nmol/l before and 42.6 +/- 3.9 nmol/l after treatment) or
      milk (2.1 +/- 0.29 nmol/l before and 2.3 +/- 0.49 nmol/l after hGH
      treatment).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506472
TI  - IGFBP-2 expression in liver and mammary tissue in lactating and pregnant ewes.
AB  - Binding proteins for the insulin-like growth factors (IGFBPs) modulate the
      actions of IGF I and IGF II. IGFBP-2 is particularly high in plasma of pregnant
      and fetal animals and in milk. We investigated the peri-lactational control of
      IGFBP-2 expression and secretion. Fifteen singleton-bearing pregnant ewes at day
      101 of gestation were injected sc twice daily for 8 days with bovine growth
      hormone (bGH) or ovine placental lactogen (oPL) both at 0.15 mg.kg-1.d-1 or
      saline. A further fifteen ewes at day 17 of lactation were injected sc twice
      daily for 5 days with bGH or oPL at 0.1 mg.kg-1.d-1 or saline. On the last day of
      injection blood samples were taken and the animals were sacrificed. Liver and
      mammary tissue samples were immediately frozen and subsequently extracted to
      provide total RNA for evaluation by Northern blot analysis using a rat IGFBP-2
      cDNA probe. Plasma samples were analysed by Western ligand blotting for IGFBP-2.
      The comparison of the two saline-treated groups (pregnant vs lactating ewe)
      revealed no difference in the plasma concentrations of IGFBP-2. IGFBP-2 mRNA
      expression in the liver of the lactating ewes was markedly increased compared to
      that in the pregnant ewes. In contrast, in mammary tissue the expression was
      significantly lower in lactating than in pregnant sheep. In pregnant animals
      treatment with bGH, but not oPL, decreased the expression of IGFBP-2 in liver.
      There was a similar trend in the lactating ewe.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506473
TI  - Isolation and partial molecular characterization of basic fibroblast growth
      factor from isolated porcine thyroid follicles and entire porcine thyroid glands.
AB  - Immunoreactive basic fibroblast growth factor (bFGF) could be isolated from the
      cytosol preparation of isolated porcine thyroid follicles as well as in the
      conditioned medium from thyroid follicles in suspension culture. A double band
      with 16,500 and 15,500 D was detected on sodium dodecyl sulfate polyacrylamide
      gel electrophoresis. In dot blot and western blot the isolated peptide was
      immunoreactive with a specific anti-bovine bFGF antibody. For further biochemical
      characterization, bFGF was isolated from entire porcine thyroid glands by
      ammonium sulfate precipitation, cation exchange chromatography and heparin
      affinity chromatography. The material obtained from all three origins was
      identical concerning affinity to heparin and immunoreactivity with the specific
      anti-bovine bFGF antibody and induced neovascularization in the chorioallantois
      membranes of chick embryos. Amino acid sequence analysis of the 16-amino-terminal
      amino acids of the isolated bFGF was in accordance with the established complete
      146-amino-acid bFGF molecule except that glycine in position 10 is replaced by
      phenylalanine. An additionally identified minor peptide presumably is an amino
      terminal-truncated form of bFGF, missing the first 15 amino acids. We conclude
      that the physiological significance of bFGF released by thyroid cells may be the
      regulation of angiogenesis during thyroid development and goiter growth.

PMID- 7506474
TI  - Tissue fixation methods alter the immunohistochemical demonstrability of
      neurofilament proteins, synaptophysin, and glial fibrillary acidic protein in
      human cerebellum.
AB  - This study has examined the effect of postmortem autolysis, type, and duration of
      fixation on neurofilament, synaptophysin, and glial fibrillary acidic protein
      (GFAP) antigen decay as demonstrated by immunohistochemistry, using a
      streptavidin-biotin peroxidase method. The system used consisted of 5 normal
      cerebellar cortices. Time intervals, temperature, mode of fixation and storage,
      and staining technique were well controlled. Anti-neurofilament antibodies
      comprised SMI-31, MNF, and BF-10 against phosphorylated epitopes, and SMI-32
      against a non-phosphorylated epitope. Bouin's and B5 fixative, and Sensofix gave
      best results, whereas formaldehyde and paraformaldehyde fixation gave much lower
      immunoreactivity. Phosphorylated neurofilament epitopes were less affected by
      aldehydes than unphosphorylated epitopes. GFAP staining was most consistent after
      Bouin fixation while the monoclonal antibody was much more sensitive to the
      fixative used than the polyclonal one. Aspecific background staining increased
      considerably after a postmortem interval of 24 hours. Synaptophysin
      immunoreactivity, as demonstrated by SY-38, proved very sensitive to prolonged
      fixation and was of poor quality following formaldehyde and paraformaldehyde
      fixation. Knowledge of antigen decay due to postmortem artifacts is essential for
      the correct evaluation of immunoperoxidase studies of autolyzed tissues that have
      been fixed and stored in different modes and for variable time interval.

PMID- 7506475
TI  - Megakaryocyte markers in myeloproliferative disorders.
AB  - Identification of megakaryocyte precursors with immunohistochemical methods in
      bone marrow trephine biopsy specimens (embedded in a plastic resin, Immuno-Bed)
      was performed from patients with blastic phase of chronic granulocytic leukaemia
      (five cases), from chronic megakaryocytic-granulocytic myelosis (four cases) and
      from acute megakaryoblastic leukaemia (11 cases). In megakaryoblasts of bone
      marrow biopsies immunohistochemical reactions using the ABC method and monoclonal
      antibodies against von Willebrand antigen and GpIIb/IIIa (CD41) were visible in
      various percentages depending on the maturation's degree of megakaryocyte
      precursors. The number of circulating blast cells determined by flow
      cytophotometry was nearly similar to those of observed in biopsies. The greatest
      bone marrow reticulin content could be detected in acute megakaryoblastic
      leukaemia cases. Despite the different clinicopathological entities, the presence
      of the same phenotype (megakaryoblasts) was associated with a short survival in
      these haematological malignancies (in CGL MKB phase 4.0, in CMGM MKB phase 4.2,
      and in AML M7 5.8 months, respectively).

PMID- 7506476
TI  - Laboratory evaluation of urinary tract infections in an ambulatory clinic.
AB  - A 4-month evaluation of ambulatory patients with a suspicion of a urinary tract
      infection was performed. Specific objectives included assessment of five urinary
      screening methods, reevaluation of the necessity of the phenylethyl alcohol plate
      (PEA), and cost-effectiveness of screening for low colony count bacteriuria.
      Urine samples were collected as midstream, clean-caught specimens. A total of 142
      samples, 87 from 79 symptomatic patients and 55 negative controls, were
      evaluated. All urine specimens were cultured using a 0.01 mL loop and a 0.001 mL
      loop onto Columbia sheep blood agar, MacConkey agar, and PEA agar. Twenty-four
      specimens (17%) were sterile, 64 (45%) were contaminated, and 54 (38%) were
      infected. Five urine screening methods were performed. These tests and their
      associated sensitivity and specificity are as follows. The Chemstrip 9 (Behring,
      Inc., Somerville, NJ) for leukocyte esterase and nitrate, 67%, 98%; microscopic
      analysis on spun urine, 79%, 93%; methylene blue stain for pyuria, 60%, 99%; Gram
      stain for pyuria, 45%, 93%; Gram stain for bacteriuria, 65%, 75%; and the
      URISCREEN (Analytab Products, Plainview, NY), 92%, 89%. Inclusion of a PEA plate
      for isolation of gram-positive organisms provided no additional information.
      Routine culture of urine samples at 10(-2) mL increased the contamination rate by
      19%.

PMID- 7506477
TI  - Chondroid chordoma--a variant of chordoma. A morphologic and immunohistochemical
      study.
AB  - In 1973, Heffelfinger and coworkers described a variant of chordoma that
      contained cartilaginous areas indistinguishable from hyaline type chondrosarcoma.
      They designated these tumors chondroid chordomas and found that they had a better
      prognosis than classic (nonchondroid) chordomas. Since that time, there has been
      an ongoing debate over whether chondroid chordoma is best considered a distinct
      clinicopathologic entity separable from chondrosarcoma or a misdiagnosed
      chondrosarcoma whose concept developed from the erroneous interpretation of
      morphology. In an attempt to clarify the issue, the authors used light microscopy
      and immunohistochemistry to study 12 chondroid chordomas, 38 classic chordomas,
      and 28 chondrosarcomas that arose in the base of the skull or spine. As a
      reference, they also analyzed the immunohistochemical profile of fetal notochord,
      ecchordosis physaliphora, and fetal hyaline cartilage. They found that all
      chondroid and nonchondroid chordomas were positive for cytokeratin, and the
      majority were also positive for epithelial membrane antigen (EMA) and
      carcinoembryonic antigen (CEA). In contrast, none of the chondrosarcomas stained
      for cytokeratin, EMA or CEA. Vimentin and S-100 were positive in more than 95% of
      both classic and chondroid chordomas and chondrosarcomas. The immunohistochemical
      profile of these tumors was similar to the pattern of immunoreactivity of their
      nonneoplastic counterparts. The authors conclude that chondroid chordomas is a
      variant of chordoma and should not be confused with chondrosarcoma. Because
      chondroid chordomas have been reported to have a better prognosis, they felt that
      this nosologic term should be preserved and that chondroid chordoma should
      continue to be a focus of clinical and pathologic study.

PMID- 7506478
TI  - Primary yolk sac tumors of the mesentery. A report of two cases.
AB  - Two yolk sac tumors that arose in the mesentery of the jejunum and the mesentery
      of the transverse colon of two male patients, aged 2 and 17 years, are reported.
      Both patients had abdominal masses. The tumors measured 9 and 11 cm in maximum
      dimension. One of them grew into the bowel lumen. Microscopically, both neoplasms
      exhibited several of the typical patterns of yolk sac tumor and stained
      immunohistochemically for alpha-fetoprotein. Both patients received chemotherapy
      postoperatively and are alive, but follow-up is short. The subject of
      extragonadal yolk sac tumors is reviewed, and histogenetic implications of their
      occasional origin in the mesentery is discussed.

PMID- 7506479
TI  - The differential diagnosis of prostatic carcinoma. Its distinction from
      premalignant and pseudocarcinomatous lesions of the prostate gland.
AB  - Prostate gland specimens account for a significant percentage of diagnostically
      challenging cases in surgical pathology practice. The understanding of prostate
      pathology has progressed, and the differential diagnosis of prostatic carcinoma
      has expanded to include possible premalignant lesions and several recently
      described pseudocarcinomatous lesions. The authors discuss the histopathology of
      prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia, review
      the evidence for their role as premalignant lesions, and discuss the criteria
      that allow for their distinction from prostatic adenocarcinoma.
      Pseudocarcinomatous lesions that must be recognized when assessing prostatic
      tissue include sclerosing adenosis, cribriform hyperplasia, mesonephric
      hyperplasia, and basal cell hyperplasia. The pathologic features and diagnostic
      challenges of these and other pseudocarcinomatous lesions are reviewed.

PMID- 7506480
TI  - The expression of histocompatibility-related leukocyte antigens in the pathway to
      cervical carcinoma.
AB  - The major histocompatibility complex probably plays a crucial role in the
      efficacy of the cellular immune response against virally infected cervical
      diseases. Therefore, the allele-specific histocompatibility-related leukocyte
      antigens (HLA) class I and II expression on normal (n = 10), premalignant (n =
      25), and malignant cervical tissue (n = 30) was investigated. No alterations in
      monomorphic or locus/allele-specific HLA class I or II expression were observed
      in normal and premalignant epithelial tissue. In cervical carcinomas, however, a
      reduced expression of HLA class I antigens was present in 70% of the cases,
      comprising a monomorphic class I loss in 20%, and an allele-specific loss in 50%
      of HLA-A2-, 66% of A3-, 56% of Bw4-, and 37% of Bw6-positive patients. De novo
      expression of class II antigens was observed in 80% of the cervical carcinomas,
      with the sublocus products being expressed in the order HLA-DR > HLA-DQ > HLA-DP.
      The authors' results show that alteration in HLA expression is a process confined
      to malignant cells, which may allow tumors to evade immune surveillance. In
      addition, these findings have to be considered as new strategies of immunotherapy
      using cytotoxic T lymphocytes are developed.

PMID- 7506481
TI  - Morphologic and quantitative changes in blood and marrow cells following growth
      factor therapy.
AB  - Sequential blood and bone marrow specimens from 53 patients receiving recombinant
      granulocyte (G-CSF) or granulocyte macrophage colony stimulating growth factor
      (GM-CSF) for neutropenia were evaluated. The blood findings were marked by a
      neutrophilia with a prominent left shift, increased azurophilic granulation,
      Dohle bodies, and an elevated leukocyte alkaline phosphatase; circulating
      myeloblasts were observed but did not exceed 2% of the leukocytes. Nuclear
      segmentation abnormalities consisting of hyposegmentation, hypersegmentation, and
      ring nuclei were noted but were not a prominent finding. A leukoerythroblastosis
      was present in 54% of patients. No consistent effect on cell lines other than
      neutrophils was found. A monocytosis was present in 12 patients, a transient
      lymphocytosis in 2 and an eosinophilia in 1. No effect was evident on basophils.
      The morphologic changes in the neutrophils in the bone marrow specimens were most
      pronounced in the early period of growth factor therapy with a relative
      neutrophil hyperplasia with a marked increase in promyelocytes and myelocytes.
      With increasing duration of therapy, the myeloid to erythroid ratio normalized
      and the percentage of promyelocytes decreased while myelocytes and band
      neutrophils increased. Thirteen patients had no response to growth factor. The
      nonresponding patients were clinically diverse; all bone marrow biopsy specimens
      in this group were virtually acellular. No differences were noted between G-CSF
      and GM-CSF.

PMID- 7506482
TI  - Application of carrier testing to genetic counseling for X-linked
      agammaglobulinemia.
AB  - Bruton X-linked agammaglobulinemia (XLA) is a phenotypically recessive genetic
      disorder of B lymphocyte development. Female carriers of XLA, although
      asymptomatic, have a characteristic B cell lineage-specific skewing of the
      pattern of X inactivation. Skewing apparently results from defective growth and
      maturation of B cell precursors bearing a mutant active X chromosome. In this
      study, carrier status was tested in 58 women from 22 families referred with a
      history of agammaglobulinemia. Primary carrier analysis to examine patterns of X
      inactivation in CD19+ peripheral blood cells (B lymphocytes) was conducted using
      quantitative PCR at the androgen-receptor locus. Obligate carriers of XLA
      demonstrated > 95% skewing of X inactivation in peripheral blood CD19+ cells but
      not in CD19- cells. Carrier status for mothers of isolated affected males could
      be assessed in 10 of 11 families: 7 women showed skewing, and 3 did not. Five
      carriers were found in six families in which there were no living affected males.
      Among all those tested, one individual's carrier status was considered to be
      indeterminate and five women were noninformative for the carrier test. Results
      obtained by the carrier test were congruent with linkage analysis (where
      applicable) using the RFLPs DXS178 and DXS94 and two newly developed polymorphic
      microsatellite markers, DXS178CA and DXS101AAT. Refinements in techniques for
      primary carrier testing and genetic mapping of XLA now make possible an ordered
      approach to diagnosis, prenatal diagnosis, and genetic counseling.

PMID- 7506484
TI  - New finding of Schinzel-Giedion syndrome: a case with a malignant sacrococcygeal
      teratoma.
AB  - We report on a boy with Schinzel-Giedion syndrome (SGS) with a previously
      unreported manifestation, a malignant sacrococcygeal teratoma. This is the second
      case of SGS to have a malignancy, as one earlier case had a hepatoblastoma. We
      postulate that the occurrence of 2 uncommon embryonic tumors among these patients
      with a rare syndrome may mean that risk of malignancy may be a component of this
      syndrome.

PMID- 7506483
TI  - Tetrasomy 9p: tissue-limited idic(9p) in a child with mild manifestations and a
      normal CVS result. Report and review.
AB  - Supernumerary isochromosomes resulting in autosomal tetrasomy are rare and have
      been described only for 12p, 18p, and 9p. Nineteen previous cases of tetrasomy 9p
      have been reported, and in 6 cases, tissue-specific mosaicism was implied with
      the i(9p) cell line present exclusively or predominantly in blood. We report on
      an infant who had apparently normal chromosomes (46,XY) on CVS. He was referred
      for genetic evaluation because of mild developmental delay and minor anomalies.
      In 75% of blood cells he had an extra isodicentric 9p chromosome (pter-->q12-
      >pter). The interpretation of tetrasomy 9p was confirmed by elevated GALT
      activity. No tetrasomy 9p cells were seen in 100 skin fibroblasts. This case
      demonstrates the tissue specific mosaicism in tetrasomy 9p which rendered the
      anomaly undetectable by CVS. It also demonstrates the mild end of the clinical
      spectrum associated with tetrasomy 9p.

PMID- 7506485
TI  - Distinctive autosomal or X-linked dominant syndrome of microcephaly, mild
      developmental delay, short stature, and distinctive face.
AB  - We report on a mother and two sons with a syndrome of microcephaly, short
      stature, a distinctive face, broad thumbs and great toes, and mild developmental
      delay. There are similarities to the patients reported by Bawle and Horton [Am J
      Med Genet 33:382-384, 1989] and Evans [Clin Genet 39:178-180, 1991] but it is not
      certain whether the patients have the same condition. Inheritance could either be
      autosomal or X-linked dominant.

PMID- 7506486
TI  - Familial occurrence of renal and mullerian duct hypoplasia, craniofacial
      anomalies, severe growth and developmental delay: a 4p deletion?

PMID- 7506487
TI  - RNA subunit of mitochondrial RNA-processing enzyme is induced by contractile
      activity in striated muscle.
AB  - A small RNA encoded within the nucleus of yeast and mammalian cells is an
      essential subunit of a mitochondrial RNA-processing endonuclease (RNase MRP) that
      generates primers for mitochondrial DNA (mtDNA) replication. We examined
      expression of MRP-RNA in specialized subtypes of mammalian striated muscles that
      differ markedly in respiratory activity and in muscles subjected to chronic
      stimulation via the motor nerve, a potent stimulus to mitochondrial biogenesis.
      MRP-RNA was more abundant in mitochondria-rich cardiac and slow-twitch skeletal
      muscles than in glycolytic fast-twitch skeletal muscles. Forced contractile
      activity resulting from nerve stimulation increased expression of MRP-RNA by 3.5
      fold within the first day and by 14-fold within 14 days. Changes in abundance of
      MRP-RNA preceded but otherwise occurred in parallel to changes in specific
      activity of citrate synthase, a marker of mitochondrial proliferation shown
      previously to correlate with mtDNA copy number in this model. Another small RNA
      (U1) also was induced transiently (1-3 days) by nerve stimulation, but such
      changes were not sustained and were of less magnitude (< 4-fold) than changes in
      MRP-RNA. These findings are consistent with the hypothesis that MRP-RNA may have
      a regulatory function with respect to mtDNA replication and mitochondrial
      biogenesis.

PMID- 7506488
TI  - Oleic acid differentially affects gap junction-mediated communication in heart
      and vascular smooth muscle cells.
AB  - The effects of oleic acid (OA) on gap junction-mediated intercellular
      communication between A7r5 cells and neonatal rat cardiac myocytes were
      determined. In A7r5 cells the extent of dye coupling was influenced in a biphasic
      manner by increasing concentrations of OA. Low concentrations of OA (0.1-1
      microM) reduced the incidence of dye coupling from 90% (in control cells) to
      approximately 50%. Further increases in OA concentration, up to 100 microM, had
      no further effect on extent of dye coupling. In contrast, dye coupling between
      cardiac myocytes was reduced to near zero levels in a linear fashion by 1-25
      microM OA. Whereas high OA concentrations reduce junctional conductance (gj)
      between heart cells to zero [J. M. Burt, K. D. Massey, and B. N. Minnich. Am. J.
      Physiol. 260 (Cell Physiol. 29): C439-C448, 1991], gj between A7r5 cells was
      decreased by a maximum of 45% by OA. These differences in OA sensitivity between
      the two cell types were not explained by differences in the rate or magnitude of
      OA uptake by the cells or by differences in the fraction of incorporated OA
      accessible to albumin washout, i.e., the plasma membrane fraction. Instead, the
      activity of the individual channel types exhibited different sensitivities to OA.
      In the presence of increasing concentrations of OA, the activities of first the
      70-pS channel population [composed of connexin40 (Cx40)] and then the 108-pS
      channel population (composed of Cx43) were diminished, leaving predominantly the
      140-pS channels (composed of Cx43) at high OA concentrations. The uncoupling
      effects of OA in both cell types could be reversed by washout with albumin
      containing solution; however, higher concentrations of albumin and more vigorous
      wash conditions were required for full recovery in the A7r5 cells. In addition,
      albumin also reversed the effects of OA on channel activity. These data suggest
      that OA binds with greater affinity to the 70- vs. 108- or 140-pS channels and
      associated with binding is reduced channel activity.

PMID- 7506489
TI  - Ionic basis of the action potential of guinea pig gallbladder smooth muscle
      cells.
AB  - Smooth muscle cells in the intact guinea pig gallbladder had a resting membrane
      potential of about -45 mV and had spontaneous action potentials that consisted of
      a rapid depolarization, a transient repolarization, a plateau phase, and a
      complete repolarization. These action potentials lasted approximately 570 ms and
      occurred at a frequency of approximately 0.4 Hz. Action potentials were abolished
      by the dihydropyridine (DHP)-sensitive Ca2+ channel blocker nifedipine (1.0
      microM) and were enhanced by the DHP-sensitive Ca2+ channel agonist BAY K 8644
      (0.5 microM). The K+ channel blockers tetraethylammonium chloride (5.0 mM) and 4
      aminopyridine (4-AP; 2.0 mM) prolonged the action potential, whereas
      charybdotoxin (100 nM), a blocker of calcium-activated potassium channels, had no
      effect. Whole cell currents were characterized in enzymatically isolated smooth
      muscle cells from the same preparation. 4-AP, a blocker of voltage-dependent K+
      channels, suppressed 70% of the outward current at 0 mV. Charybdotoxin (100 nM)
      reduced an additional 15% of the current at 0 mV. Single calcium-activated
      potassium channels were identified. The potential for half-activation of these
      channels, at a cytosolic Ca2+ concentration of 100 nM, was 66.8 mV. A fivefold
      increase in cytosolic Ca2+ resulted in a shift of the activation curve by -53 mV.
      External tetraethylammonium chloride (200 microM) reduced the mean single channel
      current by 48% at 0 mV. The whole cell outward current was abolished by
      replacement of intracellular K+ for Cs+. Ca2+ currents were inhibited by
      nifedipine and were increased by BAY K 8644. We conclude that DHP-sensitive
      voltage-dependent Ca2+ channels are responsible for the depolarization of the
      action potentials and that the repolarization is due to primarily 4-AP-sensitive
      K+ current.

PMID- 7506490
TI  - Full-length and truncated Kv1.3 K+ channels are modulated by 5-HT1c receptor
      activation and independently by PKC.
AB  - In T-cells, the Shaker-related gene, Kv1.3 encodes the type n K+ channel, whereas
      the type l channel is a product of the Shaw. subfamily gene, Kv3.1. Both these
      genes are also expressed in the brain. We have used the Xenopus oocyte
      heterologous expression system to study the modulatory effects of serotonin (5
      hydroxytryptamine, 5-HT) on both these cloned channels. In oocytes coexpressing
      the mouse 5-HT1c receptor and mouse Kv1.3 channel, addition of 100 nM 5-HT causes
      a complete and sustained suppression of Kv1.3 currents in approximately 20 min.
      In contrast, 5-HT has no effect on mouse Kv3.1 currents when coexpressed with 5
      HT1c receptor. The 5-HT-mediated suppression of Kv1.3 currents proceeds via
      activation of a pertussis toxin-sensitive G protein and a subsequent rise in
      intracellular Ca2+, but Ca2+ does not directly block the channel. Protein kinase
      (PK) C activation is not part of the pathway linking 5-HT1c receptor to Kv1.3
      channels. However, phorbol esters independently suppress Kv1.3 currents. Deletion
      of the first 146 amino acids from the NH2-terminal, containing putative tyrosine
      kinase and PKA phosphorylation sites, does not alter the time course of 5-HT
      mediated suppression of Kv1.3 currents, indicating that these residues are not
      necessary for modulation. Treatment of oocytes with calmodulin or phosphatase
      inhibitors does not alter 5-HT-mediated modulation. Collectively, these
      experiments indicate that the mouse Kv1.3 channel is capable of being modulated
      by 5-HT via 5-HT1c receptor in a G protein and Ca(2+)-dependent manner, but the
      subsequent steps in the pathway remain elusive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506491
TI  - Exercise induces a transient increase in transcription of the GLUT-4 gene in
      skeletal muscle.
AB  - Endurance exercise training elicits an increase in mitochondrial density as well
      as GLUT-4 glucose transporter protein content in skeletal muscle. Corresponding
      increases in mRNA for respiratory enzymes and GLUT-4 indicate that
      pretranslational control mechanisms are involved in this adaptive process. To
      directly test whether transcription of the GLUT-4 gene is activated in response
      to exercise training, nuclei were isolated from red hindlimb skeletal muscle of
      rats after 1 wk of exercise training (8% grade, 32 m/min, 40 min, twice/day).
      Rats were killed either 30 min, 3 h, or 24 h after the last training session.
      GLUT-4 transcription, determined by nuclear run-on analysis, was unaltered after
      30 min, increased by 1.8-fold after 3 h, but was no longer different from
      controls 24 h after exercise. A similar transient increase in GLUT-4
      transcription was evident, but less pronounced (1.4-fold), in untrained rats
      after a single bout of exercise, suggesting that the postexercise induction in
      GLUT-4 gene transcription is enhanced by exercise training. GLUT-4 protein
      content was increased 1.7-fold after 1 wk of training in the absence of any
      corresponding change in GLUT-4 mRNA, providing evidence that the initial increase
      in GLUT-4 expression involves translational and/or posttranslational control
      mechanisms. These findings demonstrate that muscle GLUT-4 expression in response
      to exercise training is subject to both transcriptional and posttranscriptional
      regulation. We propose that the increase in GLUT-4 mRNA evident with extended
      periods of training may result from a shift to pretranslational control and is
      the cumulative effect of repeated postexercise transient increases in GLUT-4 gene
      transcription.

PMID- 7506492
TI  - Induction of multidrug resistance downregulates the expression of CFTR in colon
      epithelial cells.
AB  - The epithelial cell line HT-29, which constitutively expresses the cystic
      fibrosis transmembrane conductance regulator (CFTR), was induced to become drug
      resistant by cultivation in the presence of colchicine. The gradual acquisition
      of drug resistance was associated with a corresponding increase in the expression
      of the multidrug resistance P-glycoprotein (P-gp) and a marked (> 80%) decrease
      in the constitutive levels of CFTR protein, as determined by immunoblotting. The
      reduction in CFTR content occurred at the onset of acquisition of drug resistance
      when P-gp expression was still relatively low. Reversal of drug resistance by
      removal of colchicine from the culture medium led to a 70% decrease in P-gp
      levels and a concomitant 40% increase in CFTR. The levels of other membrane
      proteins such as Na(+)-K(+)-ATPase and alkaline phosphatase remained relatively
      constant (< 26% variation). We propose that a selective downregulation of CFTR is
      elicited by acquisition of the multidrug resistance (MDR) phenotype and that
      induction of P-gp expression leads to a reversible repression of CFTR
      biosynthesis. These findings provide an experimental foundation for the
      complementary patterns of expression of the CFTR and MDR1 genes observed in vivo.

PMID- 7506493
TI  - Autoregulation of histamine synthesis through H3 receptors in isolated fundic
      mucosal cells.
AB  - Histamine plays an important role in the control of gastric acid secretion by
      activating H2 receptors located on parietal cells. In gastric mucosa, histamine
      is stored both in mast cells and in enterochromaffin-like cells, especially in
      rodents. It has been proposed that histamine may regulate its own synthesis
      and/or release through receptors pharmacologically distinct from H1- and H2
      receptor subtypes. In this article, we studied the regulation by histamine of
      histidine decarboxylase (HDC) activity (enzyme responsible for the formation of
      histamine by decarboxylation of L-histidine) in a fraction of isolated rabbit
      gastric mucosal cells enriched in mucous and endocrine cells. Histamine and (R)
      alpha-methylhistamine (H3 receptor agonist) dose dependently inhibited HDC
      activity with the same potency (mean effective concn: 32.2 +/- 0.7 and 50.5 +/-
      3.1 pM, respectively) and efficacy (35 and 36% inhibition, respectively). In
      contrast, the H2 agonist dimaprit was devoid of effect. The H3 antagonist
      thioperamide was found to decrease the histamine- or (R)-alpha-methylhistamine
      induced inhibition of HDC activity (mean ineffective concn = 28.3 +/- 1.8 and
      9.87 +/- 0.8 nM, respectively), whereas H1 (promethazine) and H2 (ranitidine)
      antagonists were unable to affect HDC activity. Moreover, high concentrations of
      thioperamide (1-10 microns) increased histamine release from these cells. All
      these results allowed us to conclude that, in gastric mucosa, histamine
      downregulates its own synthesis (and perhaps release) through the stimulation of
      autoreceptors with pharmacological characteristics of H3 receptors. However, the
      relationship between histamine synthesis and release remains unclear and needs
      further investigation.

PMID- 7506494
TI  - Alveolar macrophage secretion of a 92-kDa gelatinase in response to bleomycin.
AB  - These experiments were conducted to study the possible involvement of macrophage
      derived gelatinases in the bleomycin-induced model of pulmonary fibrosis. Normal
      rat alveolar macrophages and the rat alveolar macrophage cell line NR8383 were
      stimulated in vitro with 0-1.0 microgram/ml bleomycin for 18 h. Gelatinase
      activity in the medium was assayed on zymograms in which gelatin or collagen were
      used as substrates. Macrophages stimulated with 0.01-1.0 microgram/ml of
      bleomycin secreted significantly more of a 92-kDa gelatinase than did
      unstimulated controls. Addition of cycloheximide during stimulation decreased
      gelatinase activity by 86 +/- 4%, and activity was completely inhibited by the
      addition of EDTA to zymograms. This gelatinase degraded denatured type I collagen
      and native type IV collagen. Western blot analysis using a monoclonal mouse anti
      rat antibody demonstrated that this enzyme was the same as a metalloproteinase
      secreted by rat mammary carcinoma cells. Gelatinase secreted by macrophages in
      fibrotic lungs may enhance macrophage migration through the lung and may also be
      active in the remodeling process.

PMID- 7506495
TI  - Synthesis and vectorial export of cGMP in airway epithelium: expression of
      soluble and CNP-specific guanylate cyclases.
AB  - Guanosine 5'-cyclic monophosphate (cGMP) is an important modulator of fluid
      balance in many epithelia. We examined its metabolism in primary cultures of
      human airway epithelia. Sodium nitroprusside increased cGMP levels 30-fold,
      suggesting that the respiratory epithelium expresses a soluble guanylate cyclase;
      however, endogenous nitric oxide production was not detected. cGMP levels could
      also be increased by C-type natriuretic peptide (CNP), but not by atrial
      natriuretic peptide, brain natriuretic peptide, or Escherichia coli heat-stable
      enterotoxin, indicating expression of a CNP-specific membrane-bound guanylate
      cyclase. The one-half effective concentration for CNP was 40 nM and the maximal
      velocity was 56.7 pmol cGMP.mg protein-1.h-1. After CNP stimulation,
      approximately 60% of the total synthesized cGMP was preferentially exported from
      the polarized epithelial cells across the basolateral membrane by a probenecid
      sensitive process. Isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate
      (cAMP) export revealed a similar export pattern and probenecid sensitivity,
      although a lower efficiency of export (27% of total cAMP was exported).
      Consistent with previous reports, export of neither cyclic nucleotide was
      saturable at the concentrations tested. We conclude that the respiratory
      epithelium expresses a soluble guanylate cyclase, a CNP-specific receptor, and a
      novel vectorial cyclic nucleotide export mechanism.

PMID- 7506496
TI  - Hyalinizing clear cell carcinoma of salivary gland.
AB  - We describe 11 patients with a distinctive salivary gland neoplasm. Most of the
      patients were adult women who presented with a painless mass. Nine tumors arose
      in minor salivary glands of the oral cavity (82%). Microscopically, they were
      characterized by the formation of trabeculae, cords, islands, and/or nests of
      monomorphic clear cells that were glycogen rich and mucin negative and were
      surrounded by hyalinized bands with foci of myxohyaline stroma. Cells with
      eosinophilic and granular cytoplasm were also noted. Both cell types showed
      minimal nuclear pleomorphism and a very low mitotic index. The neoplasms all had
      infiltrative borders. Immunohistochemically, the tumor cells expressed
      cytokeratins and epithelial membrane antigen, but not S-100 protein and smooth
      muscle actin. Ultrastructurally, the tumor cells contained abundant glycogen,
      desmosomes, peripheral tonofilaments, and prominent interdigitating microvilli
      without actin myofilaments or dense bodies. These immunohistochemical and
      ultrastructural findings provide evidence of epithelial differentiation without
      myoepithelial differentiation. For these tumors, we propose the name, hyalinizing
      clear cell carcinoma (HCCC). These are low-grade malignant neoplasms. Two
      patients had ipsilateral cervical lymph node metastases at presentation, but with
      surgical excision and either preoperative or post-operative radiotherapy in three
      cases, eight of 10 patients with clinical follow-up are alive and well without
      evidence of recurrence. The mean clinical follow-up is 3.6 years, with a range of
      6 months to 11 years. One patient died as a result of surgery, another died of
      unrelated causes, and one patient was lost to follow-up.

PMID- 7506497
TI  - A nonhuman primate model for human cerebral malaria: effects of artesunate
      (qinghaosu derivative) on rhesus monkeys experimentally infected with Plasmodium
      coatneyi.
AB  - We studied the effects of artesunate on rhesus monkeys infected with Plasmodium
      coatneyi. Sixteen rhesus monkeys were divided in four groups. Group I consisted
      of three monkeys that were splenectomized and were treated with three doses
      (loading dose: 3.3 mg/kg, maintenance doses: 1.7 mg/kg) of artesunate, group II
      consisted of three monkeys that were treated with three doses of artesunate (same
      as group I), group III consisted of two monkeys that were treated with one dose
      (3.3 mg/kg) of artesunate, and group IV consisted of five untreated monkeys.
      Parasitemias of these groups ranged from 13.3% to 19.5% before treatment. Twenty
      four hours after administration, the parasitemia was reduced to 2.2% in group I
      and to < 0.1% in group II; parasitemia was lowered to 10.6% in group III only 3
      hr after drug administration. The rate of sequestration in the cerebral
      microvessels, which was 29.4% in untreated animals, was < 0.1% in groups I and II
      (24 hr after treatment), and 2.0% in group III (3 hr after treatment). These data
      clearly indicate that artesunate not only reduced parasitemia, but also reduced
      the rate of parasitized red blood cell (PRBC) sequestration in cerebral
      microvessels. In an immunohistologic study, endothelial-leukocyte adhesion
      molecule-1 (ELAM-1) was not detected in group I after treatment with artesunate,
      although the presence of CD36, thrombospondin, intercellular adhesion molecule-1,
      IgG, and C3 in the cerebral microvessels was not altered. This is the first in
      vivo study to show that artesunate interferes with continued PRBC sequestration
      in the cerebral microvessels in cerebral malaria.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7506498
TI  - Combined oral isoprinosine-intraventricular alpha-interferon therapy for subacute
      sclerosing panencephalitis.
AB  - Eighteen patients, 16 boys and 2 girls, aged 5-14 years, with subacute sclerosing
      panencephalitis (SSPE) were treated with oral isoprinosine (100 mg/kg/day) and
      intraventricular alpha-interferon 2b (Intron A, Schering Corp.), starting at
      500,000 U twice a week and later increasing to 3 million U biweekly. Minimal
      follow-up of living patients is 12 months; maximal 40 months. On the basis of the
      Neurological Disability Index (NDI) scores and staging, 8 have treatment-induced
      remissions (3 improved, 5 arrested), 4 are worse and 6 died. This 44% (8/18) rate
      of remission/improvement compares well with the 9% (1/11) remission in historical
      controls in the same institution (p = < 0.05) and 5% spontaneous remission in the
      literature. Combined oral isoprinosine-intraventricular alpha-interferon appears
      to be an effective treatment for SSPE.

PMID- 7506499
TI  - Neuroscience research: how has it contributed to our understanding of alcohol
      abuse and alcoholism? A review.
AB  - Alcohol abuse and alcoholism are the greatest substance abuse problems in the
      United States today and contribute to numerous medical and social problems. To
      deal with many of these problems, an understanding of how alcohol acts on the
      brain is extremely important. Advances in neuroscience research have provided
      significant clues about where and how alcohol works on the brain. Alcohol clearly
      acts on membrane function, altering such processes as ion movements and
      neurotransmitter interactions with their receptors. Although these alcohol
      induced alterations are presumed to relate to changes in behavior, this has not
      been clearly established. However, alcohol research is on the threshold of making
      a giant leap forward in our understanding the etiology of alcoholism.

PMID- 7506500
TI  - Obstructed migration of Purkinje cells in the developing cerebellum of the reeler
      mutant mouse.
AB  - It has been considered that cortical malformation in the brain of the reeler
      mutant mouse is due to a defect in the process of neuroblast migration during
      development. We examined the process of Purkinje cell migration in the cerebellar
      primordium of the reeler mutant immunohistochemically and electron
      microscopically, employing a specific marker for Purkinje cells and markers for
      radial glia. To facilitate the recognition of the homozygote of the reeler
      mutation (r1) at the embryonic stage, we introduced the chromosome carrying the
      autosomal semi-dominant mutation, hammer-toe (Hm), by crossbreeding and backcross
      into the heterozygote of the reeler mutation, which is an autosomal recessive and
      located on the homologous chromosome. Using this double heterozygous strain (+/rl
      Hm/+), the homozygote of rl can be selected from littermates by the normal
      appearance of the feet. Both the heterozygous rl embryos and non-carriers harbor
      the Hm locus and show the Hm phenotype as a deformity of the feet that can be
      recognized from the 15th day of gestation. In the cerebellar primordium of
      control mice, Purkinje cells migrated radially from the ventricular zone towards
      the cortex. In contrast, most of the migratory Purkinje cells remained in the
      intermediate zone, and their migration towards the cortex was obstructed in the
      cerebellum of the reeler mutant. A disorganized arrangement of both the processes
      and cell bodies of the radial glia was demonstrated in the cerebellar primordium
      of the reeler by labeling them with the antibody against tenascin, a neuron-glial
      adhesion molecule, and the monoclonal antibody 1D11, a marker for immature
      astroglia. Electron-microscopic observations revealed apposition of the migratory
      cells to the radially oriented glial processes in the intermediate zone of the
      control cerebellum. In contrast, the apposition of leading processes of the
      migratory neuroblasts to disorganized processes of the radial glia was observed
      in the intermediate zone of the reeler cerebellum. These findings suggest that
      the obstructed migration and disordered cortical alignment of Purkinje cells in
      the reeler cerebellum is due to dysgenesis and abnormal development of radial
      glia, resulting in disturbance of contact guidance in the process of Purkinje
      cell migration.

PMID- 7506502
TI  - Early development of quail heart epicardium and associated vascular and glandular
      structures.
AB  - As in the other vertebrates the epicardium of the quail embryo develops from
      proepicardial tissue located between the sinus horns and the liver primordium.
      The cuboidal cells of the coelomic lining above the proepicardium are transformed
      into mesothelial cells which in cooperation with the underlying mesenchymal cells
      elaborate a large quantity of extracellular matrix, so producing the villous
      outgrowths of the proepicardium. The mesenchymal cells of this area are attached
      to each other with typical desmosomes and have anti-alpha cytokeratin-stained
      tonofilament bundles. These cells resemble keratinocytes and are designated as
      proepicardial matrix keratinocytes. The proepicardium proliferates first in the
      sulci of the U-shaped tubular heart, and within 2 days (between stages 15-25)
      establishes the visceral layer of the epicardium. The proliferating proepicardium
      consists of gland-like tubular strands, formed by the invaginations of the
      surface mesothelial cells, mesenchymal cells, fibroblasts, angioblasts, blood
      cells and capillaries. Because of its heterogeneous structure and multiple
      functions, the proepicardium is considered a transitory organ of the developing
      heart. In the quail embryo the forerunners of the coronary vessels grow from the
      perihepatic area into the proepicardial organ, and when the epicardial covering
      is completed, but before the coronary artery orifices open, these primordial
      vessels form a subepicardial and intramural vascular network in the ventricular
      myocardium. After the completion of the epicardial covering the proepicardium
      involutes and is not seem from stage 26 onward.

PMID- 7506501
TI  - The rat renal nerves during development.
AB  - The prenatal and postnatal development of the innervation of the rat kidney has
      been investigated using immunocytochemical methods. The efferent innervation was
      studied using dopamine-beta-hydroxylase and neuropeptide Y antibodies. Calcitonin
      gene related peptide and substance P antibodies were used to investigate the
      afferent innervation. Kidneys from embryos of 14 to 20 days, from newborn rats,
      and from animals of 4, 10, 12, 21, 38, 60, and 90 days of age were studied.
      Slices of whole kidneys were analyzed, and frozen sections were used to
      investigate the location of the nerves in more detail. Both afferent and efferent
      nerves are observed inside the kidney by embryonic day 16. At birth, the afferent
      nerves are found (1) forming a rich plexus in the renal pelvis; (2) associated
      with the renal vasculature as far as the interlobular arteries (cortical radial
      arteries) and (3) in the corticomedullary connective tissue. The efferent
      innervation appears, at birth, to extend to the interlobular arteries and to the
      afferent arterioles of the perihilar juxtamedullary nephrons. The efferent
      innervation increases rapidly during the following days, and by postnatal day 21
      a distribution of the innervation similar to that of the adult is observed. While
      the afferent innervation reaches the major target regions of the kidney by birth,
      the efferent does most of its expansion into the kidney postnatally. Afferent and
      efferent fibers are found, extrarenally and intrarenally, in the same nerve
      bundles. This proximity between afferent and efferent fibers may represent
      anatomical bases for their interaction in the adult as well as during
      development.

PMID- 7506503
TI  - Postnatal development of semitendinosus muscle in the dog.
AB  - In this study the differentiation of postnatal muscle fibres in dog
      semitendinosus muscle has been characterized. Several histochemical techniques
      for myosin ATPase and metabolic activity were used in animals aged between 1 day
      and 2 months. The results show that at birth there are two types of fibre, whose
      ATPase activity gradually changes during postnatal development, so that several
      types of fibre can be identified after 2 months. These finally become the four
      types of the adult: I, IIA, IIDog, IIC. The main conclusions of the study are
      that the use of mATPase techniques is appropriate for showing the differentiation
      between muscle fibres, even at early stages of postnatal development, and that
      the origin of the four different fibres of the adult can be traced back to early
      postnatal stages.

PMID- 7506504
TI  - Transient expression of a slow-tonic MHC isoform by extrafusal fibers in the
      developing rat.
AB  - ALD 19, a monoclonal antibody that recognizes the slow-tonic myosin heavy chain
      (MHC) isoform, has been used extensively as a marker for nuclear bag intrafusal
      fibers of muscle spindles in developing and adult rats. Extrafusal fibers of
      adult rat hindlimb muscles do not express slow-tonic MHC. However, while using
      ALD 19 to trace the fate of intrafusal fibers following neonatal denervation, we
      noted that some extrafusal fibers of neonates also bound this antibody. The
      immunolabeled extrafusal fibers were a subset of slow fibers located in the deep
      axial regions of crural muscles. The same fiber subset transiently displayed a
      weak affinity for ALD 19 during the first postnatal week in normal muscles.
      Denervation at birth increased the intensity of ALD 19 immunolabelling by these
      extrafusal fibers and extended the duration of the slow-tonic immunoreactivity
      into the 2nd postnatal week, after which expression diminished or ceased.
      Demonstration that some developing extrafusal fibers have a nerve-independent
      capacity for transiently expressing slow-tonic MHC, an MHC previously though to
      be expressed only by intrafusal fibers, raises the possibility that both types of
      fiber originate from a subset of bipotential slow primary myotubes in rat
      hindlimbs.

PMID- 7506506
TI  - Taxol and recombinant human granulocyte colony-stimulating factor, an active
      regimen as initial therapy for metastatic breast cancer. A preliminary report.

PMID- 7506505
TI  - High-intensity chemotherapy with hematopoietic support in breast cancer.
AB  - Chemotherapy can produce excellent palliation for many patients with metastatic
      breast cancer. Survival impact is, however, limited, and permanent remission is
      extremely rare. There is increasing evidence that dose and dose intensity may be
      important determinants of outcome in the chemotherapy of breast cancer. Single
      courses of chemotherapy in doses requiring autologous bone marrow support produce
      high rates of objective response in patients with metastatic disease that was
      refractory to prior standard-dose therapy. When used as first chemotherapy for
      metastases or as consolidation in patients whose disease is responding to lower
      dose therapy, high-dose chemotherapy can result in prolonged disease-free
      survival for some patients. The major cause of treatment failure is relapse from
      a chemotherapy-induced complete response. Kinetic models suggest that multiple,
      rapidly cycled courses of high-dose chemotherapy might be superior to single
      applications or to multiple treatments that are widely spaced in time.
      Heretofore, the substantial toxicity of high-dose chemotherapy (up to 20%
      mortality in some early trials) has largely precluded the consideration of timely
      retreatment; however, the risk appears to have been reduced through the use of
      hematopoietic growth factors and peripheral blood progenitor cells. Our group has
      used these new technologies to develop regimens consisting of multiple cycles of
      high-dose chemotherapy that are rapidly administered. We are currently refining
      these regimens in preparation for phase II and III studies.

PMID- 7506507
TI  - Heparin-binding growth factor blockade with pentosan polysulfate.

PMID- 7506508
TI  - Angiogenesis in breast cancer. Regulation, prognostic aspects, and implications
      for novel treatment strategies.

PMID- 7506509
TI  - Chemical modifications of aminonaphthalenesulfonic acid derivatives increase
      effectivity and specificity of reverse transcriptase inhibition and change mode
      of action of reverse transcriptase and DNA polymerase alpha inhibition.
AB  - The reverse transcriptase (RT) inhibition and the specificity of 15
      aminonaphthalenesulfonic acid derivatives were examined with RT of a simian
      immunodeficiency virus derived from an African green monkey (SIVagmTYO-7). The
      two compounds with the strongest RT inhibition (NF415) or the highest specificity
      (NF345), together with suramin, were evaluated against polymerase alpha-primase
      complex from calf thymus. We have also compared the kinetics of inhibition of the
      viral and the cellular polymerase by these three compounds. While RT inhibition
      followed a mixed competitive and non-competitive mechanism, inhibition of the DNA
      polymerase alpha was competitive for suramin and non-competitive for NF415 and
      NF345. Certain structural characteristics appeared to be common for specific RT
      inhibitors.

PMID- 7506510
TI  - Substituted naphthalenones as a new structural class of HIV-1 reverse
      transcriptase inhibitors.
AB  - A novel substituted naphthalenone (TGG-II-23A) has been found that inhibits HIV-1
      infection of CEM-SS cells at concentrations that are not cytotoxic. Time of
      addition experiments indicate that TGG-II-23A functions at a stage of the HIV-1
      life cycle at or near reverse transcription. Cell free assays confirmed that TGG
      II-23A inhibits HIV-1 reverse transcriptase. Similar to other non-nucleoside
      inhibitors, TGG-II-23A was specific for HIV-1 and failed to inhibit the
      replication of HIV-2. The binding site of TGG-II-23A appears to be in close
      proximity to that of the TIBO-like inhibitors, since a TIBO-resistant HIV-1 was
      also resistant to TGG-II-23A treatment. TGG-II-23A is a mixed non-competitive
      inhibitor that exhibits the same template:primer selectivity as other non
      nucleoside inhibitors. TGG-II-23A therefore represents a new structural entry
      into the TIBO/Nevirapine class of inhibitors of HIV-1 reverse transcriptase.

PMID- 7506511
TI  - Antiviral action of trehalose dimycolate against EMC virus: role of macrophages
      and interferon alpha/beta.
AB  - Preventive treatment of mice with trehalose 6,6' dimycolate (TDM), an
      immunomodulator of bacterial origin, enhances their resistance to
      encephalomyocarditis (EMC) virus infection. The protective effect of TDM is
      totally abolished by the injection of silica particles in mice, demonstrating the
      role of macrophages in the antiviral action of TDM. In vitro, peritoneal
      macrophages from mice treated with TDM (TDM-PM) exhibit an intrinsic antiviral
      activity against EMC virus, while resident peritoneal macrophages (RES-PM) are
      permissive to this virus. Greater amounts of interferon are detected in
      supernatants of cultures of TDM-PM than of RES-PM. Neutralization of interferon
      (IFN) by addition in vitro of anti-IFN alpha/beta serum markedly reduces the
      antiviral activity of TDM-PM. These results indicate that interferon alpha/beta
      is involved in the intrinsic anti-EMC virus activity of peritoneal macrophages
      from mice treated with TDM.

PMID- 7506512
TI  - Human trophoblast interferons.
AB  - The human placental trophoblasts which constitute the first fetal cells and form
      the major cell layer of the feto-maternal interface are potent producers of
      interferons (IFNs). The IFN production is dependent on the gestational age of the
      trophoblast, type of inducer and the stage of differentiation of the
      trophoblasts. First trimester trophoblast populations produce higher levels (5-6
      times) of IFN than the third trimester trophoblasts when stimulated with viruses.
      Non-viral inducers, such as poly(rl).poly(rC), induce exclusively IFN-beta
      whereas viruses such as Sendai and Newcastle Disease Virus (NDV) induce mixtures
      of IFN-alpha subtypes and IFN-beta. Differentiation of mononuclear
      cytotrophoblasts into syncytiotrophoblasts in vitro increase the IFN production.
      High-performance and immunoaffinity chromatography of the virus-induced
      trophoblast IFN preparations resulted in the isolation of three antigenically
      distinct IFNs, namely, alpha I, alpha II1 (omega 1), and beta with molecular
      masses of 16, 22 and 24 kDa, respectively, on SDS-PAGE. The human trophoblast
      IFNs have physical and antiviral activities characteristic of the Type 1 IFNs.
      The possible roles of the trophoblast IFNs in human placental and fetal
      development are also discussed in this review.

PMID- 7506513
TI  - Lack of synergy in the inhibition of HIV-1 reverse transcriptase by combinations
      of the 5'-triphosphates of various anti-HIV nucleoside analogs.
AB  - 3'-Deoxy-3'-azidothymidine (AZT) has been shown to synergistically inhibit the
      replication of human immunodeficiency virus type 1 (HIV-1) in cell culture when
      combined with several other 2',3'-dideoxynucleoside analogs. In an effort to
      understand the biochemical mechanism of this synergy, we have examined the effect
      of combinations of the 5'-triphosphate of AZT (AZT-TP) with either ddCTP, ddATP,
      or the 5'-triphosphate of the carbocyclic analog of 2',3'-didehydro-2',3'
      dideoxyguanosine (carbovir) on both the RNA-directed and DNA-directed DNA
      polymerase activity of HIV-1 reverse transcriptase. Kinetic studies, which
      evaluated the ability of these combinations to competitively inhibit the enzyme,
      showed that AZT-TP could not bind to the enzyme with either the RNA or DNA
      template at the same time as either of the other three inhibitors. None of these
      analogs could affect the incorporation of another analog into the DNA chain by
      the HIV-1 reverse transcriptase. These results indicated that synergistic
      inhibition of the HIV-1 reverse transcriptase is not responsible for the
      synergistic antiviral activity seen in cell culture with combinations of these
      nucleoside analogs.

PMID- 7506514
TI  - The rates of macromolecular chain elongation modulate the initiation frequencies
      for transcription and translation in Escherichia coli.
AB  - Here we show that most macromolecular biosynthesis reactions in growing bacteria
      are sub-saturated with substrate. The experiments should in part test predictions
      from a previously proposed model (Jensen & Pedersen 1990) which proposed a
      central role for the rates of the RNA and peptide chain elongation reactions in
      determining the concentration of initiation competent RNA polymerases and
      ribosomes and thereby the initiation frequencies for these reactions. We have
      shown that synthesis of ribosomal RNA and the concentration of ppGpp did not
      exhibit the normal inverse correlation under balanced growth conditions in batch
      cultures when the RNA chain elongation rate was limited by substrate supply. The
      RNA chain elongation rate for the polymerase transcribing lacZ mRNA was directly
      measured and found to be reduced by two-fold under conditions of high ppGpp
      levels. In the case of translation, we have shown that the peptide elongation
      rate varied at different types of codons and even among codons read by the same
      tRNA species. The faster translated codons probably have the highest cognate tRNA
      concentration and the highest affinity to the tRNA. Thus, the ribosome may
      operate close to saturation at some codons and be unsaturated at synonymous
      codons. Therefore, not only translation of the codons for the seven amino acids,
      whose biosynthesis is regulated by attenuation, but also a substantial fraction
      of the other translation reactions may be unsaturated. Recently, we have obtained
      results which indicate that also many ribosome binding sites are unsaturated with
      their substrate, i.e. with ribosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506515
TI  - CSF biochemistries, glucose metabolism, and diurnal activity rhythms in
      alcoholic, violent offenders, fire setters, and healthy volunteers.
AB  - BACKGROUND: There is an extensive literature describing a central serotonin
      deficit in alcoholic, impulsive, violent offenders and fire setters. In the
      present study, we investigated biochemical concomitants of impulsivity and
      aggressiveness, and the physiological consequences of reduced central serotonin
      turnover. METHODS: Forty-three impulsive and 15 nonimpulsive alcoholic offenders
      and 21 healthy volunteers were studied in the forensic psychiatry ward of a
      university psychiatric department. The subjects underwent lumbar punctures and
      oral glucose and aspartame challenges, and their diurnal activity rhythm was
      measured with physical activity monitors. Discriminant function analyses were
      used to investigate psychophysiological and biochemical concomitants of
      aggressive and impulsive behaviors. RESULTS: Alcoholic, impulsive offenders with
      antisocial personality disorder had low mean cerebrospinal fluid (CSF) 5
      hydroxyindoleacetic acid (5-HIAA) and corticotropin levels and high mean CSF
      testosterone concentrations. Compared with healthy volunteers, they showed
      increased physical activity during the daytime. Alcoholic, impulsive offenders
      with intermittent explosive disorder had a low mean CSF 5-HIAA concentration and
      blood glucose nadir after an oral glucose challenge, and desynchronized diurnal
      activity rhythm. Healthy volunteers had mean CSF 5-HIAA concentrations that were
      intermediate between those of alcoholic, impulsive and nonimpulsive offenders.
      Alcoholic, nonimpulsive offenders had a significantly higher mean CSF 5-HIAA
      concentration than all the other groups, including healthy volunteers.
      CONCLUSIONS: In the present sample, a low CSF 5-HIAA concentration was primarily
      associated with impulsivity and high CSF testosterone concentration, with
      aggressiveness or interpersonal violence.

PMID- 7506516
TI  - Personality profiles and state aggressiveness in Finnish alcoholic, violent
      offenders, fire setters, and healthy volunteers.
AB  - BACKGROUND: Based on clinical observations in a series of studies on Finnish
      alcoholic, violent offenders, we asserted that the impulsive offenders
      represented an extreme group of type 2 alcoholics. We also observed that these
      subjects were vulnerable to hypoglycemia after the administration of oral glucose
      load. Furthermore, we believe that while being hypoglycemic, the impulsive
      offenders are particularly irritable and aggressive. In the present study, we
      addressed these issues by studying psychological trait and state variables in a
      new group of violent offenders and fire setters, and age- and sex-matched healthy
      volunteers. METHODS: Fifty-eight alcoholic, violent offenders and impulsive fire
      setters and 21 healthy volunteers were administered the Karolinska scales of
      personality and the Rosenzweig picture frustration test after an oral aspartame
      and glucose challenge. RESULTS: The psychological test results and the criminal
      histories of the offenders, together with biochemical measurements, suggest that
      a low 5-hydroxyindoleacetic acid concentration in cerebrospinal fluid in the
      alcoholic offenders is associated with irritability and impaired impulse control,
      and a high free testosterone concentration in cerebrospinal fluid is associated
      with increased aggressiveness, monotony avoidance, sensation seeking,
      suspiciousness, and reduced socialization. CONCLUSION: Finnish alcoholic,
      impulsive offenders have personality profiles characteristic of Scandinavian
      early-onset male alcoholics with antisocial traits, who have been also referred
      to as type 2 alcoholics.

PMID- 7506517
TI  - Suicidality and 5-hydroxyindoleacetic acid concentration associated with a
      tryptophan hydroxylase polymorphism.
AB  - BACKGROUND: To examine whether the tryptophan hydroxylase (TPH) gene, which codes
      for the rate-limiting enzyme in the biosynthesis of serotonin, may be a factor
      influencing serotonin turnover and behaviors controlled by serotonin. METHODS:
      Using a polymerase chain reaction-based method, TPH genotype was determined in
      DNA samples from 56 impulsive and 14 nonimpulsive, alcoholic, violent offenders
      and 20 healthy volunteers. RESULTS: In the behaviorally extreme impulsive group,
      we observed a significant association between TPH genotype and cerebrospinal
      fluid 5-hydroxyindoleacetic acid (5-HIAA) concentration. No association of TPH
      genotype with impulsive behavior was detected. The polymorphism was also
      associated with a history of suicide attempts in all violent offenders,
      independent of impulsivity status and cerebrospinal fluid 5-HIAA concentration.
      CONCLUSION: In some individuals, a genetic variant of the TPH gene may influence
      5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal
      behavior.

PMID- 7506518
TI  - Are stress hormones and serotonin related to aggression in primates?

PMID- 7506520
TI  - Lectin-mediated enhancement of dengue virus infection in a mouse macrophage cell
      line Mk1.
AB  - Treatment of a mouse macrophage cell line Mk1 with pokeweed mitogen (PWM) either
      before or during but not after virus inoculation resulted in an enhancement of
      dengue virus (DV) infection. The infection enhancement was primarily due to an
      increase in the number of DV-infected cells but not to increased virus production
      in a cell. These results suggested that PWM treatment mediated increased DV
      binding and/or penetration to Mk1 cells, thereby resulting in the infection
      enhancement. N-acetylglucosamine (GlucNAc) did not suppress PWM-mediated
      enhancement of DV infection when added to Mk1 cells after PWM treatment was done,
      although GlucNAc clearly suppressed the effect of PWM when added simultaneously
      with PWM. The results implied the possibility that the PWM-mediated increase in
      viral binding/penetration was not due to a cross-linking by PWM between DV and a
      cell-surface receptor, but due to another mechanism, presumably exposure of a
      masked DV receptor(s). The DV receptor, unidentified as yet, involved in the PWM
      mediated infection enhancement appeared to have no relation with IgG Fc receptors
      that are known to be involved in antibody-mediated enhancement of DV infection.

PMID- 7506519
TI  - Deduced amino acid sequences of the haemagglutinin of H5N1 avian influenza virus
      isolates from an outbreak in turkeys in Norfolk, England.
AB  - The deduced amino acid sequences of the haemagglutinins of avian influenza
      viruses, isolated from an outbreak in turkeys in Norfolk, England in 1991/92,
      were determined by PCR amplification and cycle sequencing. Both the highly
      pathogenic and avirulent isolates had the same cleavage site sequence with
      multiple-basic amino acids, which normally would be expected only for the former.
      Clones derived by plaque picking from the highly pathogenic isolate ranged from
      low to very high pathogenicity in vivo and these, and the original isolates,
      showed nucleotide and amino acid variation at one or more of five possible sites,
      none of which were at the cleavage site. None of these site variations correlated
      with pathogenicity, suggesting that the factor responsible for the suppression of
      the expected effects of the multiple-basic amino acid haemagglutinin cleavage
      site in the avirulent isolate may not have been part of the haemagglutinin amino
      acid sequence.

PMID- 7506521
TI  - [Effects of thromboxane A2 and prostaglandin I2 on the release of chemical
      mediators from human peripheral leukocytes].
AB  - To investigate the effects of thromboxane (Tx) A2 and prostaglandin (PG) I2 on
      the release of chemical mediators, we studied the effects of TxA2 mimetic U-46619
      and PGI2 on the release of histamine (HA), leukotriene (LT) C4/D4/E4 (peptide
      LTs) and LTB4 from stimulated human peripheral leukocytes. We measured the levels
      of those mediators in the supernatant fluid from leukocyte suspensions stimulated
      by calcium ionophore A23187 (Ca-I, 10(-6) M) with U-46619 or PGI2. U-46619 did
      not affect the release of HA, peptide-LTs or LTB4 from leukocytes stimulated by
      Ca-I. The release of HA from leukocytes induced by Ca-I was inhibited
      significantly by PGI2 (p < 0.05). PGI2 also significantly inhibited the release
      of peptide-LTs (p < 0.05) and LTB4 (p < 0.01) from leukocytes. These results
      indicate that TxA2, an arachidonic acid cyclooxygenase metabolite does not affect
      the release of HA, peptide-LTs and LTB4 from leukocytes, but that PGI2 inhibits
      the release of these mediators induced by Ca-I.

PMID- 7506522
TI  - Asynchronous reformation of individual kallikrein-related secretory proteinases
      in rat submandibular glands following degranulation by cyclocytidine.
AB  - Time scales for the reformation of the secretory granules in granular tubules and
      their constituent proteinases were assessed after inducing a massive
      degranulation by intraperitoneal injection of cyclocytidine in conscious animals.
      The minimum working dose of cyclocytidine to produce the maximum degranulation
      and depletion of proteinase activity, at 3 h after injection, was 75 mg/kg.
      Histologically, although most granular tubule cells then appeared to be
      extensively degranulated, isolated individual cells showing little or no
      degranulation always persisted. Acinar cells also showed some depletion of
      secretory material. At 15 h after injecting cyclocytidine the formation of new
      granules had begun in the granular tubule cells, but it was not extensive or
      uniform in adjacent cells; however, the acinar cells already appeared to be
      regranulated. The pattern of granule reformation in granular tubule cells
      progressed gradually, so that 7-10 days after cyclocytidine-induced degranulation
      the cells were mostly packed with granules and showed similar appearances to
      those of normal resting control glands. Individual proteinases in extracts of the
      glands were assayed specifically using fluorogenic oligopeptide amidase
      substrates, with and without appropriate inhibitors. This revealed a 95%
      reduction in total proteinase activity 3 h after cyclocytidine (75 mg/kg). In the
      same extracts, acinar peroxidase was reduced by 28%. Peroxidase levels recovered
      to control values within 15 h after cyclocytidine but recovery of proteinases
      progressed more gradually and did not occur uniformly for the different
      constituent proteinases. Tissue kallikrein (rK1) showed the most rapid recovery
      and had reached levels approaching normal within 3 days.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7506523
TI  - Effects of hormones and cytokines on stimulation of adenylate cyclase and
      intracellular calcium concentration in human and canine periodontal-ligament
      fibroblasts.
AB  - Adenylate cyclase was stimulated by prostaglandin E2 (PGE2) and parathyroid
      hormone-related protein (PTHrP) in both these types of fibroblast and by
      calcitonin gene-related protein (CGRP) in the human fibroblasts in vitro. PGE2 (1
      microM), CGRP (1 microM), and PTHrP (1 microM) stimulated adenylate cyclase up to
      50-fold, 10-fold and 9-fold, respectively. Calcitonin (CT), substance P (SP),
      interleukin-1 beta (IL-1 beta), and transforming growth factor-beta 1 (TGF beta
      1) had no effect on adenylate cyclase in either fibroblast. Intracellular Ca2+
      (iCa2+) was measured in individual fibroblasts from the periodontal ligament
      using Indo-1 and an adherent cell analysis and sorting interactive laser
      cytometer. Ionomycin (3 microM) caused a transient rise of iCa2+ in all human and
      canine fibroblasts tested. The mean percentage increase in iCa2+ in response to
      ionomycin was 820 and 840% for human and canine fibroblasts, respectively. The
      human fibroblasts responded to PGE2 (1 microM) by an increased iCa2+
      concentration; the mean percentage increase in iCa2+ was 187%. SP caused a less
      pronounced increase in iCa2+ in the human fibroblasts (56%). CGRP and SP caused a
      similar response in the canine fibroblasts. The mean percentage increase in iCa2+
      in response to SP and CGRP was 95 and 78%, respectively. PTH, PTHrP, platelet
      activating factor, CT, and IL-1 beta had no effect on iCa2+ in either type of
      fibroblast. The data indicate that cAMP and calcium have roles as intracellular
      secondary messengers in the action of PGE2, SP, CGRP, and PTHrP in fibroblasts of
      human and canine periodontal ligament.

PMID- 7506525
TI  - 'Two hats can be hard to wear'.
AB  - I wear my two hats proudly now, that of a mother of a child with a disability and
      that of a doctor. My 'mother hat' is not removable. I have tried to separate
      myself from it at times, but that is too painful--it is a part of me. My 'doctor
      hat' is rather like a smart balaclava. It is appropriate and useful in specific
      situations. It can be pulled over my eyes to hide how I feel and, at times,
      offers some protection. But it can also obscure my vision and sometimes causes me
      to stumble over obstacles I may otherwise have successfully negotiated.

PMID- 7506524
TI  - The fate of genetically marked human oral keratinocytes in vitro.
AB  - The fate of the progeny of human oral gingival keratinocytes was mapped in
      stratified epithelial tissues in vitro by following the expression of a marker
      gene in genetically related clones. Oral epithelial progenitor cells were
      genetically marked at high efficiency by transducing them with a retrovirus
      vector that carried the gene for a histochemically detectable product,
      Escherichia coli beta-galactosidase (beta-gal). These cells were then grown in
      submerged cultures and on collagen rafts at the air-liquid interface to
      demonstrate the distribution of genetically marked cells in a differentiating
      tissue in vitro. The dynamics of transduced cells showed that clonally related
      cells were arranged in discrete units of labelled cells and these clusters were
      defined as 'clonal proliferation units'. The size and configuration of these
      units were related to the proliferative potential and differentiating capacity of
      the cell that was initially transduced. This model demonstrates the relation
      between clonally related cells and tissue architecture for oral keratinocytes in
      vitro.

PMID- 7506526
TI  - Sulphydryl groups in the template-primer-binding domain of murine leukaemia virus
      reverse transcriptase. Identification and functional analysis of cysteine-90.
AB  - Treatment of murine leukaemia virus reverse transcriptase with benzophenone 4
      maleimide inactivates DNA polymerase activity, but has no effect on the RNAase H
      function. Kinetic measurements indicated that benzophenone 4-maleimide is a
      competitive inhibitor with respect to template-primer binding, but is non
      competitive with respect to dNTP binding. Enzyme modified with benzophenone 4
      maleimide cannot bind template-primer or primer alone, as judged by u.v.-mediated
      cross-linking of radiolabelled substrates. Of the eight cysteine residues in
      murine leukaemia virus reverse transcriptase, only two were modified by
      benzophenone 4-maleimide, which were identified as Cys-90 and Cys-310 by
      comparative tryptic-peptide mapping and amino acid composition analysis.
      Inclusion of template-primer or primer alone in the modification mixture
      protected only Cys-90 from modification by benzophenone 4-maleimide. To
      investigate the role of Cys-90 in detail, we converted it to alanine by site
      directed mutagenesis. The mutant enzyme, however, exhibited no loss either of DNA
      polymerase or of RNAase H activity. These results indicate that Cys-90 is located
      in a domain of murine leukaemia virus reverse transcriptase that binds template
      primer, but may not have a direct role in the enzymic function of the enzyme. Ala
      90 mutant murine leukaemia virus reverse transcriptase is at least 10-fold more
      susceptible to heat inactivation than is the wild-type enzyme, which suggests
      that Cys-90 in murine leukaemia virus reverse transcriptase may play a role in
      maintaining structural integrity.

PMID- 7506527
TI  - Defining the roles of the threefold channels in iron uptake, iron oxidation and
      iron-core formation in ferritin: a study aided by site-directed mutagenesis.
AB  - This paper aims to define the role of the threefold intersubunit channels in iron
      uptake and sequestration processes in the iron-storage protein, ferritin. Iron
      uptake, measured as loss of availability of Fe(II) to ferrozine (due to
      oxidation), has been studied in recombinant human H-chain ferritins bearing amino
      acid substitutions in the threefold channels or ferroxidase centres. Similar
      measurements with recombinant horse L-chain ferritin are compared. It is
      concluded that significant Fe(II) oxidation occurs only at the H-chain
      ferroxidase centres and not in the threefold channels, although this route is
      used by Fe(II) for entry. Investigations by Mossbauer and u.v.-difference
      spectroscopy show that part of the iron oxidized by H-chain ferritin returns to
      the threefold channels as Fe(III). This monomeric Fe(III) can be displaced by
      addition of Tb(III). Fe(III) also moves into the cavity for formation of the iron
      core mineral, ferrihydrite. Iron incorporated into ferrihydrite becomes
      kinetically inert.

PMID- 7506528
TI  - Analysis of carbohydrate-protein interactions with synthetic N-linked
      neoglycoconjugate probes.
AB  - Recently we have describe a simple efficient chemical method of generating an
      asparagine side-chain linker with beta-stereochemistry at the anomeric position
      of neutral oligosaccharides. We now report the 1-N-glycyl beta-derivatization of
      sialylated saccharides. Several neoglycoconjugates formed using these N-linked
      inter-mediates were investigated for their usefulness in probing carbohydrate
      protein interactions. First, biotinyl derivatives of two xylose/fucose class
      plant-type oligosaccharides purified from horseradish peroxidase were effective
      in demonstrating the carbohydrate specificity of polyclonal anti-(horseradish
      peroxidase) antibodies. Secondly, a fluorescein-labelled asialo- and
      digalactosylated biantennary complex sugar was synthesized and shown to bind to a
      Ricinus communis agglutinin column. This galactose-specific recognition was
      abolished by treating this fluorescein-labelled oligosaccharide with jack bean
      beta-galactosidase. Finally, two 1-N-glycyl beta-saccharide derivatives were
      modified with thiophosgene to form their corresponding isothiocyanate
      derivatives. Coupling of these isothiocyanate derivatives of sugars to BSA, amino
      derivatized polystyrene plates and glass-fibre discs resulted in multiple sugar
      presentation. The binding of an anti-N-acetylglucosamine monoclonal antibody to
      N,N'-diacetylchitobiose residues presented on BSA and solid supports was shown by
      e.l.i.s.a. Similarly the binding of concanavalin A to asialo-, agalactosylated
      biantennary complex oligosaccharide residues attached to BSA was demonstrated by
      a competitive e.l.i.s.a. Our results demonstrate that N-linked neoglycoconjugates
      could be made readily available and they are valuable tools for the detailed
      analyses of carbohydrates and carbohydrate-binding proteins.

PMID- 7506529
TI  - The Escherichia coli cysG promoter belongs to the 'extended -10' class of
      bacterial promoters.
AB  - The Escherichia coli cysG promoter has been subcloned and shown to function
      constitutively in a range of different growth conditions. Point mutations
      identify the -10 hexamer and an important 5'-TGN-3' motif immediately upstream.
      The effects of different deletions suggest that specific sequences in the -35
      region are not essential for the activity of this promoter in vivo. This
      conclusion was confirmed by in vitro run-off transcription assays. The DNAase I
      footprint of RNA polymerase at the cysG promoter reveals extended protection
      upstream of the transcript start, and studies with potassium permanganate as a
      probe suggest that the upstream region is distorted in open complexes. Taken
      together, the results show that the cysG promoter belongs to the 'extended -10'
      class of promoters, and the base sequence is similar to that of the P1 promoter
      of the E. coli galactose operon, another promoter in this class. In vivo,
      messenger initiated at the cysG promoter appears to be processed by cleavage at a
      site 41 bases downstream from the transcript start point.

PMID- 7506530
TI  - Four monoclonal antibodies inhibit the recognition of arylsulphatase A by the
      lysosomal enzyme phosphotransferase.
AB  - The critical step in the sorting of lysosomal enzymes is their recognition by a
      phosphotransferase in the Golgi apparatus. The topogenic sequences responsible
      for the recognition by this enzyme have so far only been defined for the
      lysosomal protease cathepsin D. We have generated four monoclonal antibodies
      directed against lysosomal arylsulphatase A (ASA). These antibodies inhibit the
      recognition of ASA by the phosphotransferase in vitro and thus define a region of
      topogenic sequences in the ASA polypeptide. The antibodies do not interfere with
      the enzymic activity nor with pH-dependent dimerization of ASA. The epitopes
      recognized by the antibodies have been located in the second quarter of the ASA
      polypeptide using chimeric mouse-human ASA molecules. Three of the monoclonal
      antibodies bind to identical or closely adjacent epitopes, which are formed by
      the interaction of amino acid residues 165-184 and 202-240. The fourth antibody
      recognizes a different epitope within amino acids 256-265.

PMID- 7506531
TI  - Induction of tyrosine phosphorylation and T-cell activation by vanadate peroxide,
      an inhibitor of protein tyrosine phosphatases.
AB  - Rapid tyrosine phosphorylation of key cellular proteins is a crucial event in the
      transduction of activation signals to T-lymphocytes. The regulatory role of
      protein tyrosine phosphatases (PTPases) in this process was explored by studying
      the effects of a powerful PTPase inhibitor, vanadate peroxide (pervanadate), on
      the activation cascade of Jurkat human leukaemic T-cells. Pervanadate induced
      activation of the tyrosine kinases lck and fyn (4- and 3-fold respectively) and a
      dramatic increase in tyrosine phosphorylation of cellular proteins, notably
      phospholipase C gamma 1. After this event, we observed a rise in intracellular
      Ca2+ concentration, corresponding to an influx. This effect required surface
      expression of the CD45 PTPase and was not observed in CD45-deficient variants of
      Jurkat cells. In the CD45-negative variant, the effect of pervanadate on tyrosine
      phosphorylation was globally decreased and some phosphorylated substrates were
      specifically missing. Pervanadate also stimulated transcription of the c-fos gene
      and accumulation of its mRNA as well as several other hallmarks of T-lymphocyte
      activation such as surface expression of the CD69 antigen and the interleukin 2
      receptor alpha-chain (CD25). Pervanadate synergized with signals delivered by T
      cell antigen receptor engagement or by a phorbol ester to induce interleukin 2
      production. Pervanadate activated NF-kappa B, as shown by an increase in DNA
      binding activity of this transcription factor. We thus conclude that PTPases play
      a crucial role in the negative regulation of signal transduction culminating in T
      lymphocyte activation. Moreover, induction of tyrosine phosphorylation appears
      sufficient per se to initiate a complete activation programme.

PMID- 7506532
TI  - Heat-inducible proteins that react with antibodies to chaperonin60 are localized
      in the nucleus of a fish cell line.
AB  - We report in the present paper that proteins which react with a polyclonal
      antibody (pAb) raised against the heat-shock protein chaperonin60 (cpn60) were
      revealed by indirect immunofluorescence in the nucleus of a fish (fathead minnow,
      Pimephales promelas) cell line after heat-shock. This immunoreactive cpn60
      associated with the nucleolus and with discrete foci. An increased abundance of
      two nuclear proteins of approx. 57 and 42 kDa, present in approximately equal
      amounts, was detected by Western blotting using an anti-cpn60 pAb as a probe
      during the same time period that cpn60 was revealed in the nucleus. These
      proteins also reacted with a monoclonal antibody (mAb) against human cpn60 but
      did not react with an mAb against the cytoplasmic chaperonin, TCP1. The kinetics
      of translocation and pattern of nuclear localization of this immunoreactive cpn60
      differed from that of stress70, another major family of heatshock proteins. We
      suggest that these nuclear immunoreactive cpn60 proteins are members of the cpn60
      family and that they play a chaperone role in folding and assembly of proteins in
      the nucleus which is distinct from that of stress70.

PMID- 7506533
TI  - Nicotinamide inhibits nitric oxide synthase mRNA induction in activated
      macrophages.
AB  - Nitric oxide (NO) is a potent mediator involved in many biological functions
      including inflammation and non-specific immunity. Murine macrophages possess the
      prototype of high-output NO synthase which is not constitutively expressed but
      induced within a few hours by immunological stimuli. In this study, we explored
      the possibility of controlling the activity of the inducible NO synthase by
      interfering with the transduction signal which triggers its induction, in the RAW
      264.7 macrophage cell line. We found that nicotinamide, an inhibitor of ADP
      ribosylation, prevented NO synthase induction in RAW 264.7 cells after
      stimulation with interferon gamma (IFN-gamma) and lipopolysaccharide (LPS).
      Furthermore, the level of NO synthase mRNA was measured by Northern-blot analysis
      and we found that nicotinamide prevents expression of NO synthase mRNA in IFN
      gamma- and LPS-stimulated cells. Nicotinamide was also found to inhibit other
      macrophage functions expressed in response to IFN-gamma, i.e. tumour necrosis
      factor secretion and the expression of the Ia antigen of the major
      histocompatibility complex. Analysis of the pattern of ADP-ribosylated proteins
      revealed that nicotinamide as well as cholera toxin prevented the ADP
      ribosylation of a 107-117 kDa protein found constitutively ADP-ribosylated in
      stimulated and non-stimulated macrophage extracts. Together, our results indicate
      ADP-ribosylation as a crucial point of the signalling pathway which leads to NO
      synthase mRNA induction.

PMID- 7506534
TI  - Preparation of unoccupied thyroid-hormone receptor.
AB  - Thyroid hormone (3,5,3'-tri-iodothyronine; T3) regulates gene expression through
      binding to its specific receptor in the nucleus. In euthyroid animals, roughly
      half of all receptors are occupied by the hormone. Nuclear extracts thus yield
      mixtures of occupied and unoccupied receptors. We present here a simple method
      for transforming occupied receptors into unoccupied ones. In vitro, the T3
      receptor complex dissociated in a half-dissociation time exceeding 100 h at 0
      degrees C, and at temperatures that accelerated the dissociation the receptor was
      quickly inactivated. Long-chain-fatty-acyl-CoAs, on the other hand, greatly
      accelerated the dissociation of T3-receptor complex at 0 degree C. The receptor
      was extracted from rat liver nuclei, incubated with oleoyl-CoA to release the
      bound hormone, and passed through a small column of Lipidex, which strongly
      adsorbed both oleoyl-CoA and the dissociated hormone. The receptor was recovered
      in the flow-through fraction in its unoccupied form, as seen by the results of
      DEAE-Sephadex column chromatography and the loss of all previously bound
      [125I]T3. The maximum T3-binding capacity of the unoccupied receptor was about
      1.5-fold that of the untreated sample, and the dissociation constant was
      unaltered. The results suggest that most nuclear thyroid-hormone receptors
      occupied by the hormone were transformed into unoccupied ones. From the T3
      binding capacity before and after oleoyl-CoA treatment, the in vivo T3 occupancy
      of the receptor was estimated. The procedure is easy to perform, and the method
      should be useful for studies of unoccupied receptors.

PMID- 7506535
TI  - Acute 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure results in enhanced
      tyrosylphosphorylation and expression of murine hepatic cyclin dependent kinases.
AB  - An increase in tyrosine phosphorylation of two hepatic S9 proteins migrating at
      34 and 33 kDa that cross-reacted with anti-PSTAIR antibody on immunoblots was
      seen 24 h after administration of a single dose of 0.25, 0.5, 1 or 2 micrograms
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg to C57BL/6J female mice. Two
      hepatic S9 proteins migrating at 34 and 33 kDa that cross-reacted with anti-cdc2
      C-terminus antibody on immunoblots were observed in corn oil control mice;
      increased expression of these proteins was seen with increasing doses of TCDD. A
      maximal increase in expression of 3-times the control was observed at 1 and 2
      micrograms TCDD/kg for both p34 and p33. The stimulation of enhanced
      tyrosylphosphorylation and expression of cyclin dependent kinases p34cdc2 and
      p3cdk2 by TCDD is consistent with a mechanism of action of TCDD toxicity
      associated with stimulation of cellular proliferation.

PMID- 7506536
TI  - Characterization of a fusion protein composed of the extracellular domain of c
      kit and the Fc region of human IgG expressed in a baculovirus system.
AB  - The extracellular domain of c-kit, which is the receptor for stem cell factor
      (SCF), was fused genetically to the Fc portion of human immunoglobulin G1. This
      chimeric protein, c-kitFc, was then expressed in the baculovirus system. The
      fusion product was secreted into the serum-free culture medium as a soluble
      dimeric form of approximately 210 Kda. The recombinant protein was easily
      purified by protein A affinity chromatography at approximately 25 micrograms
      protein per ml of medium. Binding assay and cross-linking assay showed that the
      fusion protein retained high affinity for binding SCF (Kd = 0.3 nM). Addition of
      the chimeric protein into the culture medium of SCF-dependent cells inhibited
      cell proliferation in a dose-dependent manner. These results suggest that the
      dimeric c-kitFc protein can be used as an antagonist of SCF for the study of
      hematopoietic progenitor cells.

PMID- 7506537
TI  - Lithium and tacrine increase the expression of nitric oxide synthase mRNA in the
      hippocampus of rat.
AB  - The expression of nitric oxide synthase mRNA and the enzyme activity were studied
      in the hippocampus of rats treated with lithium chloride (LiCl; 12 mEqkg-1 i.p.)
      and tacrine (5 mgkg-1 i.p.). In comparison to vehicle treated animals, mRNA
      signal was augmented by 2-fold 24 h after administration of LiCl and by 4-fold 15
      min after tacrine. In LiCl pretreated rats, tacrine yielded a 6-fold mRNA
      increase and this was prevented by corticosterone (35 mgkg-1, given i.p. 30 min
      before tacrine). Combined administration of LiCl and tacrine also produced an
      approx. 80% increase in Ca(2+)-calmodulin-dependent nitric oxide synthase
      activity. The present results represent the first demonstration that in the
      hippocampus mRNA expression of constitutive brain nitric oxide synthase can be
      augmented with consequent increase in nitric oxide synthesis.

PMID- 7506538
TI  - The chemokine, eotaxin, activates guinea-pig eosinophils in vitro and causes
      their accumulation into the lung in vivo.
AB  - Eotaxin is a novel C-C chemokine purified from the bronchoalveolar lavage (BAL)
      fluid of actively sensitised guinea-pigs after aerosol allergen challenge. In
      this study we show that eotaxin induced a dose-dependent increase in both
      intracellular-free calcium concentration ([Ca2+]i) and aggregation of guinea-pig
      eosinophils in vitro. Intradermally injected eotaxin induced the accumulation of
      [111In]eosinophils in naive guinea-pig skin in vivo, without oedema-inducing
      activity; the latter emerging in separate BAL fluid HPLC fractions. Aerosol
      exposure of naive guinea-pigs to eotaxin in vivo caused a selective increase in
      eosinophils in BAL fluid. Thus, eotaxin activates guinea-pig eosinophils in vitro
      and causes a selective eosinophil accumulation in the lung in vivo. Eotaxin and
      related molecules are potentially important endogenous signalling substances in
      allergic reactions in vivo.

PMID- 7506539
TI  - Identification of cytochromes P450 1A2, 2A1, 2C7, 2E1 in rat glioma C6 cell line
      by RT-PCR and specific restriction enzyme digestion.
AB  - Reverse transcription (RT)/polymerase chain reaction (PCR) was used to detect the
      expression of six isoforms of cytochrome P450 which belong to five P450
      subfamilies in rat glioma C6 cell line. P450 1A2, 2A1, 2C7, 2E1 were identified
      by RT-PCR in all samples, including untreated cells as well as cells treated with
      phenobarbital (PB) or benzo(a)anthracene (BA). P450 3A and 2C11 were not detected
      in our glioma samples although they were detected in liver tissues in our
      previous study. To confirm proper PCR products, various restriction enzymes were
      used to digest the PCR fragments and the expected digestion patterns were
      obtained. These results demonstrate for the first time that glioma C6 cells,
      representing a single cell type of rat central nervous system (CNS), contain a
      P450-dependent metabolism system which seems important for understanding drug
      metabolism, neurotransmission as well as tumor etiology and chemotherapy in
      brain.

PMID- 7506540
TI  - Characterization by cDNA cloning of the mRNA of human ribosomal protein L8.
AB  - From a lambda UNI-ZAP XR cDNA library derived from poly(A)+RNA of human ovarian
      granulosa cells a cDNA clone pHG51 was isolated. Sequence analysis showed
      significant homology to the C-terminal region of rat ribosomal protein L8 cDNA.
      The 5'-end of the cDNA was completed by PCR with cloned total cDNA. Aligning of
      DNA sequences from PCR clones with the sequence of the pHG51 insert yielded the
      full-length cDNA. From the open reading frame of the cDNA an amino acid sequence
      for a polypeptide of 257 residues was derived, which was identical with rat
      ribosomal protein L8 and also possessed a high degree of identity to ribosomal
      proteins L8 of other species. It is therefore assumed that the characterized cDNA
      represents the mRNA of the human ribosomal protein L8. Southern analysis revealed
      that human ribosomal protein L8 is specified by multi copy genes.

PMID- 7506541
TI  - Selective expression of the glutamate receptor channel delta 2 subunit in
      cerebellar Purkinje cells.
AB  - The primary structure of a putative subunit of the mouse glutamate receptor
      channel, designated as the delta 2 subunit, has been deduced by cloning and
      sequencing the cDNA. The delta 2 subunit has four putative transmembrane segments
      characteristic for neurotransmitter-gated ion channels, and shares 56% amino acid
      sequence identity with the delta 1 subunit of the mouse glutamate receptor
      channel and 14-24% identity with the subunits of the AMPA-, kainate- or NMDA
      selective glutamate receptor channel. RNA blot and in situ hybridization analyses
      show that the delta 2 subunit mRNA is localized in cerebellar Purkinje cells.
      Furthermore, immunoblot and immunohistochemical analyses suggest that the delta 2
      subunit protein is actually expressed in vivo in Purkinje neurons. The selective
      localization of the delta 2 subunit in Purkinje cells may imply a role of the
      delta 2 subunit in Purkinje cell-specific function such as the cerebellar LTD.

PMID- 7506542
TI  - A 4-amino-2-hydroxybutyrate activating enzyme from butirosin-producing Bacillus
      circulans.
AB  - An enzyme catalyzing a 4-amino-2-hydroxybutyrate dependent ATP-PP(i)-exchange
      reaction has been partially purified from butirosin-producing cells of B.
      circulans by ammonium sulfate fractionation, gel filtration or sucrose gradient
      centrifugation and ion exchange chromatography on QAE-sepharose. No reaction was
      found with 4-aminobutyrate and diaminobutyrate. The protein coeluted with GroEL,
      which has been identified by alignment of the internal sequence KDGVITVEESK. A
      molecular mass of about 1,5 MDa has been estimated for the complex by gradient
      centrifugation. In SDS-polyacrylamide gels a protein band with an estimated size
      of about 500 KDa correlated with the enzyme activity. The activity was not found
      in non-producing cells and a non-producing mutant of B. circulans with an
      insertional inactivation in the butB gene.

PMID- 7506543
TI  - Monoclonal antibodies against heparin-binding growth factor-1: neutralization of
      biological activity and recognition of specific amino acid sequence.
AB  - A panel of three monoclonal antibodies against heparin-binding growth factor-1
      (HBGF-1) was obtained. These antibodies, Ab-47 alpha, Ab-15, Ab-29, were able to
      recognize HBGF-1 but not HBGF-2. One of the antibodies, Ab-47 alpha, was
      identified as a HBGF-1 neutralizing antibody on the basis of its ability to
      inhibit the binding of [125I]HBGF-1 to receptors on HepG-2 cells and the
      proliferation of fetal bovine heart endothelial cells induced by HBGF-1. Ab-15
      reacted with truncated HBGF-1(Mr = 16,000), intact HBGF-1(Mr = 18,000) and mutant
      HBGF-1U which lacks a putative nuclear translocation sequence (amino acid
      residues 21 to 27 of HBGF-1). Ab-29 reacted with only truncated HBGF-1 and was
      thought to recognize the putative nuclear translocation sequence of HBGF-1. The
      three monoclonal antibodies did not inhibit the binding of [125I]HBGF-1 to
      heparin. These data indicate that each monoclonal antibody recognizes a distinct
      epitope of HBGF-1 and identifies them as useful reagents for evaluating
      functional domains and biological roles of HBGF-1.

PMID- 7506544
TI  - Fibroblast growth factor-1 induces phosphofructokinase, fatty acid synthase and
      Ca(2+)-ATPase mRNA expression in NIH 3T3 cells.
AB  - Polypeptide growth factors act in part by inducing the expression of specific
      proteins that perform functions critical to cell cycle progression. We have used
      a differential display technique to identify genes that are expressed at higher
      levels following fibroblast growth factor (FGF)-1 (acidic FGF) stimulation of
      quiescent murine NIH 3T3 fibroblasts. Three such genes--liver (B-type)
      phosphofructokinase (PFK), fatty acid synthase (FAS) and sarco(endo)plasmic
      reticulum Ca(2+)-ATPase type 2 (SERCA2)--are described in this report. The level
      of FAS and SERCA2 mRNA expression is increased rapidly after FGF-1 addition; in
      contrast, PFK mRNA is induced with kinetics more typical of delayed-early genes.
      These results indicate that enhanced expression of the PFK, FAS and SERCA2
      proteins may be important for FGF-1-stimulated cell proliferation.

PMID- 7506545
TI  - Induction of tyrosine phosphorylation in human B lineage cells by crosslinking MB
      1 molecule of B cell receptor-related heterodimer complex.
AB  - B cell antigen receptor is composed of immunoglobulin and associated MB-1 and
      B29. Here, we found that anti-human MB-1 stimulation induced tyrosine
      phosphorylation in immature B cells (FL4.4 and Nalm-6) but not in mature B cells
      (Daudi). Coprecipitated complex with the heterodimer component in Daudi and Nalm
      6 contained the kinase molecule(s) which act on the heterodimer protein, while
      the complex in early lymphoid cell with germ line antigen receptor genes (FL4.4)
      did not. Candidate Fyn and Lyn are expressed in Nalm-6 and Daudi but are not
      expressed in FL4.4. These results suggested that src-type tyrosine kinases as Fyn
      and Lyn are responsible for the phosphorylation of MB-1 and B29 heterodimer, but
      anti-MB-1 stimulation can induce tyrosine phosphorylation reaction mediated by
      other kinase molecule(s) in the progenitor type cells.

PMID- 7506547
TI  - Association of RNA with human papillomavirus E7 protein of type 16 but not type
      6b.
AB  - Nonfused human papillomavirus (HPV) type 16 and 6b E7 proteins were expressed in
      E. coli and fractionated by ion exchange and gel filtration chromatography. The
      E7 protein of type 6b was purified, but that of type 16 was found to be
      associated with RNA molecules which could not be excluded by repeated
      chromatography. The type 16 E7 protein in CaSki cells was also associated with
      RNA molecules of the same size.

PMID- 7506546
TI  - SCF/c-kit receptor-mediated arachidonic acid liberation in rat mast cells.
      Involvement of PLD activation associated tyrosine phosphorylation.
AB  - We have previously demonstrated PLD activation via c-kit receptor activation in
      rat peritoneal mast cells (Koike et al. 1993, J. Immunol. 151,359-366). In this
      study, the mechanism of arachidonic acid (AA) release in stem cell factor (SCF)
      stimulation was investigated. Genistein, a protein tyrosine kinase inhibitor, was
      found to inhibit the AA release in SCF-stimulated cells, whereas pretreatment
      with vanadate, a protein tyrosine phosphatase inhibitor, enhanced the AA release.
      Propranolol, an inhibitor of phosphatidate (PA) phosphohydrolase, repressed both
      AA liberation and 1,2-diacylglycerol (1,2-DG) formation. Short pretreatment with
      phorbol myristate acetate blunted the SCF-induced AA liberation. These results
      indicate that 1,2-DG generated via the phospholipase D pathway activated by
      tyrosine phosphorylation is a principle source for AA released in response to SCF
      in mast cells.

PMID- 7506548
TI  - Thromboembolic complications after arthroscopy of the knee.
AB  - Arthroscopy of the knee has always been associated with a low risk of
      complications, including thromboembolism. Therefore, few studies have been
      concerned with the matter. We present two case reports and a review of the
      available literature concerning thromboembolic complications after arthroscopy.

PMID- 7506549
TI  - Recognition of pathogenic Yersinia enterocolitica by crystal violet binding and
      polymerase chain reaction.
AB  - Cefsulodin-Irgasan-Novobiocin (CIN) agar is used for the selective isolation and
      enumeration of Yersinia enterocolitica from clinical specimens and food. The
      medium contains crystal violet and about 1 mmol l-1 calcium and can be used for
      the phenotypic characterization of strains that carry a virulence plasmid. At 32
      degrees C, irrespective of pathogenicity, colonies are translucent with a pale
      pink centre surrounded by a transparent border ('bullseye'), while at 37 degrees
      C pathogenic strains grow as calcium-dependent microcolonies which, because of
      crystal violet binding, are intensely coloured. These results were confirmed by
      the polymerase chain reaction with primers directed at the virF gene, which is
      present only in pathogenic strains of Y. enterocolitica. Pathogenic strains of Y.
      enterocolitica can be recognized by growth at 37 degrees C on Yersinia selective
      agar.

PMID- 7506550
TI  - Superantigens: bacterial and viral proteins that manipulate the immune system.

PMID- 7506551
TI  - Peptide binding to major histocompatibility complex molecules.

PMID- 7506552
TI  - Reversion of a polymerase-defective integrated HIV-1 genome.
AB  - The 8E5 clonal cell line, derived from HIV-1-infected CEM cells, carries a
      single, reverse transcriptase (RT)-defective copy of an integrated HIV genome.
      The absence of RT production is a consequence of a frame shift in the pol gene,
      due to the addition of a single base at position 3241. We report here that 8E5
      cells produce an infectious virus that can be serially passaged on CD4+ lymphoid
      cells. This virus (8E5R) is RT positive, but displays a slow replication profile,
      together with a reduced cytopathic effect. The nucleotide sequence of a segment
      of the pol region produced by PCR amplification of DNA from 8E5R-infected cells
      shows that the single nucleotide insertion characteristic of the 8E5 genome had
      been corrected. The same reversion event was also found to occur in most single
      cell clones derived from the 8E5 cell line. Because this cell line is used in
      many laboratories, notably as a standard for PCR quantitation, and is generally
      considered as unable to produce infectious virus, our findings should prompt
      investigators to use particular care in the handling of these cells.

PMID- 7506553
TI  - Molecular mimicry accompanying HIV-1 infection: human monoclonal antibodies that
      bind to gp41 and to astrocytes.
AB  - Monoclonal antibodies that bound to HIV gp41 and cross-reacted with astrocytes
      were recovered from the blood of three patients infected with HIV-1. Mapping of
      the specificity of these monoclonal antibodies, using synthetic gp41 peptides,
      located their epitope to amino acids 644-663 and established their conformation
      dependence. Six other human monoclonal anti-HIV antibodies were found to bind to
      HIV gp41 or gp120 but not to reactive astrocytes in brain tissue. Sharing of
      linear or conformational protein determinants between disparate viral and host
      proteins is termed molecular mimicry. The consequences of such mimicry by anti
      viral antibodies interacting with astrocytes may play a role in the dementia of
      AIDS patients since a major function of astrocytes is to maintain the appropriate
      milieu for neuronal function. The finding of such cross-reactive antibodies adds
      to the evidence for a possible autoimmune pathogenesis in some of the disease
      manifestations accompanying HIV infection.

PMID- 7506554
TI  - Costimulatory properties of the human CD4 molecule: enhancement of CD3-induced T
      cell activation by human immunodeficiency virus type 1 through viral envelope
      glycoprotein gp120.
AB  - This study was designed to investigate the T cell costimulatory activity of
      ligands binding to different regions on the human CD4 molecule. We assayed the
      costimulatory properties of a panel of CD4 MAbs, intact HIV, and viral envelope
      glycoproteins in CD3-induced activation of resting T cell subpopulations. Our
      data using MAbs reveal epitope-specific variations in the functional activities
      of CD4 MAbs under specific conditions in which CD3 and CD4 molecules are co-cross
      linked. We show that both naive and memory CD4+ T cell subsets are susceptible to
      CD4-mediated costimulation, which overcomes the functional differences between
      the two cell populations in responsiveness to CD3 MAbs. We show for the first
      time that, analogous to CD4 MAbs, preparations of HIV and viral envelope
      glycoprotein gp120 are also potent costimulators of T cell proliferation and IL-2
      production. On the basis of these results we propose possible mechanisms for
      polyclonal cell activation in the course of HIV infection and suggest that viral
      inhibitory and costimulatory effects may together disrupt the normal balanced
      function of the immune system, leading to AIDS.

PMID- 7506555
TI  - Use of the recombinant chimera proteins, LacZ-Env and Gag-Env, for immunological
      studies on HIV-1 infection.
AB  - To use Env proteins as antigens for detection of the human immunodeficiency virus
      type-1 (HIV-1) antibodies, we attempted to overexpress the Env proteins in
      Escherichia coli. To study the epitopes in the Env proteins recognized by the
      sera of HIV carriers, various regions of the proviral DNA encoding the Env region
      were fused to the 3' end of the lacZ gene. The immunoblotting analysis of the
      LacZ-Env(512-611) and LacZ-Env(721-826) proteins with the 41 positive sera
      revealed that the former and the latter immunologically reacted with 100 and 78%
      of the sera, respectively. To avoid rare false-positive reactions due to the LacZ
      moiety of the fusion protein, we attempted to express the Env(512-611) alone or
      Gag-Env(512-611) under the control of bacteriophage T7 promoter. Although we
      could express only a low level of the Env(512-611) peptide in E. coli, we
      succeeded in producing large amounts of the Gag(121-406)-Env(512-611) and Gag(308
      406)-Env(512-611) proteins as chimeric proteins. Both of these chimera proteins
      strongly reacted with the 41 positive sera. We purified these proteins and
      analyzed the immunological reactivity by dot blot with the 60 positive sera and
      the 84 normal sera. As little as 20 ng of the dotted proteins was enough for the
      reaction with the positive sera, whereas as much as 320 ng of them did not show
      false-positive reactions with the normal sera. We obtained highly purified Gag
      Env proteins with highly specific seroreactivity, which should be useful for
      diagnosis and prognosis.

PMID- 7506556
TI  - A potent, neutralizing human monoclonal antibody against a unique epitope
      overlapping the CD4-binding site of HIV-1 gp120 that is broadly conserved across
      North American and African virus isolates.
AB  - A human monoclonal antibody (HuMAb), 5145A, against HIV-1 gp120 was isolated from
      an asymptomatic, seropositive hemophiliac. The epitope of this HuMAb was
      destroyed by reduction of gp120 disulfide bonds, but not by removal of N-linked
      carbohydrates. This epitope overlaps the CD4-binding site of gp120, because
      binding of 5145A to gp120 is inhibited by soluble CD4 and by 1125H, a previously
      described HuMAb directed toward the CD4-binding site. However, the 5145A epitope
      differs from those of 1125H and other anti-CD4-binding site HuMAbs previously
      described, as documented by the viral strain specificity of 5145A and its
      reactivity with a panel of gp120 mutants. Specifically, 5145A reacted with 14 of
      15 HIV-1 isolates tested, including 9 isolates from the Central African Republic,
      6 of which were not recognized by 1125H. Partial epitope mapping of 5145A, using
      a series of gp120 mutants, demonstrated its lack of sensitivity to mutations in
      residues 257 and 427, contrasting with a marked sensitivity to mutations in
      residues 368 and 370. This pattern of reactivity distinguishes its epitope from
      that of any HuMAb against the CD4-binding site region described to date. In
      addition, 5145A exhibited potent and essentially equivalent neutralization of the
      MN, SF-2, IIIB, and RF strains and possessed significant neutralizing activity
      against three of three African strains tested. Finally, 5145A synergistically
      neutralized the MN and SF-2 strains of HIV-1 when combined with 4117C, a HuMAb
      against the V3 loop. The broad strain specificity and potent neutralizing
      activity of 5145A, together with its ability to synergize with an anti-V3 loop
      HuMAb in neutralizing HIV-1, indicate that 5145A has excellent potential as a
      passive immunotherapeutic agent against HIV-1.

PMID- 7506557
TI  - CD44 and its role in tumour progression and metastasis.

PMID- 7506558
TI  - Granulocyte colony-stimulating factor treatment of leucopenia during fractionated
      radiotherapy.
AB  - 11 patients suffering from an isolated leucopenia during fractionated
      radiotherapy were treated with granulocyte colony stimulating factor (G-CSF). 4
      of the patients received radiotherapy alone, and 7 patients received concomitant
      chemotherapy. G-CSF treatment was initiated at the occurrence of leucopenia and
      maintained for the duration of radiotherapy. The applied daily dose was 5
      micrograms/kg subcutaneously. 10 of the 11 treated patients reacted with an
      increased leucocyte count, from an average of 1342 leucocytes per microliter (+/-
      502/microliters) to 24,568 leucocytes per microliter (+/- 950/microliters).
      Neutrophil counts increased on average from 64.9% (+/- 13.9%) to 91.1% (+/- 2.3%)
      (n = 7). In 1 patient thrombocytopenia occurred during the continued
      radiotherapy. 1 other patient reacted with an unexplained fall of leucocytes
      after two doses of G-CSF and one fraction of mediastinal irradiation. Side
      effects observed during G-CSF treatment consisted of mild bone pain (1/11) and
      transient increases of serum alkaline phosphatase levels (4/11). Our observations
      indicate that G-CSF treatment is well tolerated during continuous fractionated
      radiotherapy. Therefore, we conclude that G-CSF can be used clinically to
      alleviate neutropenia caused by radiotherapy or by combined radio-chemotherapy.

PMID- 7506559
TI  - Cytotoxic effect of interferon on primary malignant tumour cells. Studies in
      various malignancies.
AB  - It is a well established fact that interferon (IFN) can inhibit cell growth, but
      only recently has it been found that IFN can exert a direct cytotoxic effect on
      primary tumour cells. This was shown in malignant cells from patients with
      multiple myeloma. In this study the influence of IFN on the viability of primary
      malignant cells from patients with different malignancies was studied. As
      previously described a direct cytotoxic effect of IFN on multiple myeloma cells
      was observed. No major effects on cell viability could be found in malignant
      cells from patients with lymphoma, chronic lymphocytic leukaemia, hairy cell
      leukaemia, chronic myelogenous leukaemia and carcinoma. This indicates that the
      direct cytotoxic effect of IFN in multiple myeloma may be relatively specific for
      this malignancy. It could be due to a specific differentiation stage in the
      myeloma cells, specific genetic alterations and/or abrogation of an
      autocrine/paracrine loop.

PMID- 7506560
TI  - Insulin-like growth factor (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) in
      the plasma of children with Wilms' tumour.
AB  - Insulin-like growth factors (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) have
      been measured in plasma of children with Wilms' tumour. The mean levels for total
      serum IGF-I and -II were not significantly altered in Wilms' tumour as compared
      with normal control plasma. However, the chromatographic profiles for IGF-I and 
      II in these groups were different with regard to the presence of IGF binding
      proteins and high molecular weight forms of IGFs; the high molecular weight form
      (9-15 kD) of IGF-II was significantly reduced in Wilms' tumour. Levels of IGFBP-2
      were substantially elevated in serum from Wilms' tumour patients (1025 +/- 112
      ng/ml compared with 416 +/- 44 ng/ml in controls), and inversely correlated with
      the levels of high molecular weight forms of IGF-II. We suggest that IGFBP-2
      measurements might be of value as a marker for monitoring this type of tumour,
      either as an adjunct to diagnosis or surveillance of tumour growth during
      therapy.

PMID- 7506561
TI  - Regulation of insulin-like growth factor binding proteins in ovarian cancer cells
      by oestrogen.
AB  - Insulin-like growth factor-I (IGF-I), its receptor and its binding proteins are
      expressed by ovarian cancer cells. In this study, we examined oestradiol (E2)
      regulation of IGF-I and IGF binding proteins (IGFBP) in an oestrogen-responsive
      ovarian cancer cell line, PE04. In serum-free conditions, PE04 cell monolayer
      growth was increased 1.64-fold by 3 nmol/l E2 compared with controls, although
      IGF-I mRNA levels were not increased. In contrast to IGF-I mRNA, IGFBP mRNA was
      regulated by E2. E2 caused a marked decrease in IGFBP-3 RNA, but IGFBP-2, -4 and 
      6 levels were only minimally depressed. IGFBP-5 mRNA levels were increased by E2.
      Tamoxifen had less effect on IGFBP mRNA regulation. Ligand blotting showed that
      E2 reduced IGFBP levels in conditioned media. IGFBP RNA was also detected in
      human ovarian tissue samples. Thus, IGFBP expression can be regulated in
      oestrogen-responsive ovarian cancer by E2.

PMID- 7506562
TI  - Study of the expression and function of the tumour-associated antigen CaMBr1 in
      small cell lung carcinomas.
AB  - The expression of the epithelial antigen recognised by the MBr1 monoclonal
      antibody (CaMBr1) was studied on 161 small cell lung carcinoma (SCLC) biopsies. A
      correlation between the marker expression and the overall survival of the
      patients was found. To investigate the possible role of CaMBr1 in tumour
      aggressiveness, the in vivo and in vitro growth capabilities of different SCLC
      cell lines, in relation to the antigen expression, were analysed. The CaMBr1
      positive cell lines displayed a higher growth potential in comparison to CaMBr1
      negative cells. The biochemical nature of CaMBr1 was analysed in terms of enzyme
      sensitivity, molecular weight and comparison with other glycoproteins expressed
      by SCLC cells. The results indicated the trypsin sensitivity of the molecule, and
      sialic acid hiding of the CaMBr1 epitope. The increase of MBr1 reactivity after
      neuraminidase treatment suggests that the CaMBr1 epitope expressed in the SCLC
      cell line is carried by a sialoglycoprotein.

PMID- 7506564
TI  - Expression and dynamic modulation of the human granulocyte colony-stimulating
      factor receptor in immature and differentiated myeloid cells.
AB  - In this study we have examined the expression and modulation of the human
      granulocyte colony-stimulating factor (G-CSF) receptor (R) in immature and
      differentiated myeloid cells using a 125I labelled human G-CSF analogue (TG50).
      Equilibrium binding data revealed a single affinity class of receptor on all cell
      types expressing G-CSFR (KD 235-606 pM) with neutrophils expressing 2883 +/- 672
      Rs/cell. Rapid internalization of surface receptor-bound ligand at 37 degrees C
      was detected in both immature cells (U937) and neutrophils with > 70% of
      specifically bound ligand internalized within 5 min. Concentration-response data
      showed that the level of occupancy of neutrophil G-CSFRs by ligand at 37 degrees
      C was approximately 5-fold greater than predicted by equilibrium binding data and
      correlated closely with concentration-response data for biological activity. Re
      expression of G-CSFRs following down-regulation by internalization was not
      detected. Down-regulation of the neutrophil G-CSFR by several agents including
      granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor
      (TNF), lipopolysaccharide (LPS), f-met-leu-phe (fMLP), phorbol ester (TPA) and
      C5a was observed at 37 degrees C but not at 4 degrees C. In contrast, G-CSFRs on
      immature myeloid cells were significantly down-regulated by TPA only.
      Differentiation of myeloid leukaemic cell line HL-60 with DMSO, a frequently used
      model of granulocytic differentiation, was associated with a significant
      reduction in G-CSFR expression (11 +/- 5% of control) whereas treatment with
      retinoic acid led to increased G-CSFR expression (161 +/- 3%).

PMID- 7506563
TI  - Temperature and risk factors for ischaemic heart disease in the Caerphilly
      prospective study.
AB  - OBJECTIVE: To examine the associations between air temperature and risk factors
      for ischaemic heart disease. METHOD: Data on risk factors are available from up
      to 2036 men in the Caerphilly Prospective Heart Disease Study. Daily temperatures
      were obtained from the Meteorological Office. Relations between these were
      examined by regression. RESULTS: The coldest month of the year has a mean
      temperature that is 16 degrees C lower than that in the warmest month. A fall in
      temperature of this magnitude is associated with higher blood pressures (by 3-5
      mm Hg) and a lower concentration of high density lipoprotein cholesterol (by 0.08
      mmol/l). The most important effects however, seem to be on the haemostatic
      system. Fibrinogen is 0.34 g/l higher in the coldest month than in the warmest (p
      < 0.001) and alpha 2 macroglobulin, a protein that inhibits fibrinolysis, is also
      raised. Platelet count is increased by 30% of a standard deviation and the
      sensitivity of platelets in whole blood to adenosine diphosphate is increased by
      cold. CONCLUSIONS: These effects on haemostasis, together with the effect on
      blood pressure, could explain a large part of the increase in ischaemic heart
      disease in the winter but are unlikely to explain much of the difference in
      mortality within different areas of England and Wales.

PMID- 7506565
TI  - Acute myeloid leukaemia blast cells bind to human endothelium in vitro utilizing
      E-selectin and vascular cell adhesion molecule-1 (VCAM-1).
AB  - The adhesion of acute myeloid leukaemia (AML) blast cells to human umbilical vein
      endothelial cells (HUVECs) was investigated in vitro. Adhesion of blast cells
      from 10 cases of AML to unstimulated and interleukin-1 beta (IL-1) stimulated
      HUVECs was similar to or greater than that of control neutrophils. The extent to
      which endothelial E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were
      involved in this adhesive process was investigated using blocking monoclonal
      antibodies to these proteins. In the majority of cases studied (7/8), anti-E
      selectin significantly inhibited adhesion to IL-1 stimulated endothelium (26-65%
      inhibition) and in 5/8 cases so did anti-VCAM-1 (maximum of 31% inhibition). All
      cases were found to express the sialylated Lewis x antigen and very late
      activation antigen-4, ligands for E-selectin and VCAM-1 respectively. Our results
      indicate that leukaemic blast cells adhere to human endothelium and that there
      are E-selectin and, to a lesser extent, VCAM-1-dependent components to this
      process. Such adhesive interactions are likely to confer on AML blast cells the
      ability to migrate across the vascular wall and so to establish extravascular
      disease.

PMID- 7506566
TI  - Clonal chronic lymphocytic leukaemia-like B lymphocytes in the blood of patients
      with cutaneous T-cell disorders.
AB  - A population of B cells with characteristics of chronic lymphocytic leukaemia was
      found in the peripheral blood of four patients who presented with cutaneous
      infiltration of atypical CD4+ T cells with cerebriform nuclei. The B cells had a
      low density of immunoglobulin on their surface membrane, expressed CD5
      positivity, and showed monoclonality based on the restriction to either kappa or
      lambda light chains. In one patient with tumourous pleiomorphic CD4+CD30- T-cell
      lymphoma of the skin, it was the first manifestation of a concomitant B-cell non
      Hodgkin's lymphoma of low-grade malignancy. In three other patients with reactive
      atypical T-cell erythroderma, there was no evidence for the coexistence of a B
      cell malignancy. The number of CD5+ B cells decreased in two erythroderma
      patients with clinical remission of the cutaneous lesions. It is speculated that
      the presence of a monoclonal B cell population in patients with T-cell disorders
      of the skin is due either to a reactive process possibly conferring some
      protective effect, or a response to an unknown stimulus produced by the T cells.

PMID- 7506567
TI  - Antibodies against terminal galactosyl alpha(1-3) galactose epitopes in patients
      with idiopathic myelofibrosis.
AB  - Sera from patients with myelofibrosis were analysed for circulating antibodies
      against an antigenic determinant characterized by two molecules of galactose in
      alpha 1-3 linkage (anti-Gal antibodies). 50% of patients were found to have
      values above the 90th percentile of the values of control sera chosen as a cut
      off. The median level of the antibodies was significantly higher than the value
      detected in normal controls, but no difference could be found between patients
      with idiopathic myelofibrosis and those with myelofibrosis associated to a
      chronic myeloproliferative disorder. Anti-Gal antibodies were found to correlate
      with disease activity and with platelet count whereas no correlation was detected
      with other haematological parameters. Furthermore, for evaluation of disease
      activity, determination of serum anti-Gal antibodies was a sensitive and specific
      parameter. We conclude that humoral immunity against Gal alpha 1-3Gal may provide
      a sensitive tool to detect disease activity in patients with idiopathic
      myelofibrosis and may be important for understanding its pathogenesis.

PMID- 7506568
TI  - Detection of an epitope specific for the dissociated form of glycoprotein IIIa of
      platelet membrane glycoprotein IIb-IIIa complex and its expression on the surface
      of adherent platelets.
AB  - Glycoproteins (GPs) IIb and IIIa form a Ca(2+)-dependent complex in platelet
      membrane and change their conformation upon platelet activation and dissociation
      of the complex. A new anti-GPIIIa monoclonal antibody (mAb), CRC54, is described
      which could distinguish different conformational states of GPIIIa. This antibody
      (i) precipitated GPIIb-IIIa from platelet Triton X-100-lysate, (ii) recognized
      the GPIIIa band in Western blotting of platelet SDS-lysate, and (iii) did not
      react with platelets from a Glanzmann's thrombasthenia patient lacking GPIIb
      IIIa. Immunoblotting of chymotryptic digestion products of purified GPIIb-IIIa
      has shown that CRC54 epitope is located within residues 1-100 at the N-terminus
      of GPIIIa. CRC54 bound weakly to platelets in the presence of Ca2+ and Mg2+, 2.34
      +/- 0.28 x 10(3) molecules per platelet at saturation. The same level of binding
      was observed without any divalent cations in the medium. However, binding of
      CRC54 was increased by several times after treatment of platelets with EDTA,
      10.04 +/- 0.28 x 10(3) molecules per platelet. Increase of CRC54 binding
      correlated with the dissociation of GPIIb-IIIa complex which was followed by the
      decrease of the binding of another mAb, CRC64, directed against complex-specific
      epitope of GPIIb-IIIa. Binding of CRC54 to platelets was changed neither by
      platelet activation in suspension with thrombin or ADP nor by the occupancy of
      GPIIb-IIIa ligand binding site with GRGDSR peptide. However, binding was
      significantly stimulated by platelet adhesion to polystyrene plastic. As measured
      using 51Cr-labelled platelets, binding of 125I-CRC54 to adherent platelets in the
      presence of divalent cations was about 4 times higher than to platelets in
      suspension, 8.68 +/- 0.48 x 10(3) per platelet. This increase was not due to the
      dissociation of GPIIb-IIIa since complex-specific antibody CRC64 still bound
      effectively to the surface of adherent platelets. The data obtained indicated
      that: (1) CRC54 recognized an epitope specific for the dissociated form of
      GPIIIa; (2) the CRC54-reactive epitope of GPIIIa is also expressed on the surface
      of adherent platelets.

PMID- 7506569
TI  - Image analysis studies of the degree of irreversible deformation of sickle cells
      in relation to cell density and Hb F level.
AB  - We analyzed, quantitatively by image analysis, the degree of irreversible
      deformation of red cells (SS cells) from patients with homozygous sickle cell
      disease, and studied the relationships among the degree of irreversible cell
      deformation, cell density, and Hb F level. SS cells from 25 patients (aged 1-36
      years) whose Hb F levels ranged from 2.5% to 40.0%, were fully oxygenated and
      then were separated into four fractions by density centrifugation. Every fraction
      was studied for morphology and Hb F content. We found that the irreversible
      deformation of SS cells from the circulation occurred mainly by elongation and
      that the degree of elongation was extremely variable. We also found that in the
      cells of patients with Hb F levels < 20% the degree of irreversible elongation
      increases as cell density increases, suggesting that dehydration occurs
      concomitantly with irreversible elongation. Statistical analysis (Student t test)
      indicated that there were significant differences (P = 0.008 or < 0.001) in the
      degree of elongation among density-fractionated SS cells from patients with Hb F
      < 20%, although there was no significant difference (P > 0.1) among those from
      patients with Hb F > or = 20%. We also found that cell density increased as Hb F
      level of the density fraction decreased in all patients with Hb F < 20% but not
      always in those with Hb F > or = 20%. This suggests that cells with lower Hb F
      levels are selectively susceptible to dehydration. Furthermore, we found that the
      mean degree of irreversible elongation decreases linearly with increasing levels
      of Hb F and reaches the normal range at 21-24%. Since the degree of irreversible
      deformation of SS cells quantified by image analysis is directly related to cell
      density, and inversely to Hb F levels, mechanical stress or membrane damage
      caused by Hb S polymerization may be an important factor in the formation of
      dense cells in vivo.

PMID- 7506570
TI  - Diagnosis of paroxysmal nocturnal haemoglobinuria by phenotypic analysis of
      erythrocytes using two-colour flow cytometry with monoclonal antibodies to DAF
      and CD59/MACIF.
AB  - We investigated the relationship between the complement lysis sensitivity test
      and two-colour flow cytometric analysis using monoclonal antibodies to decay
      accelerating factor (DAF) and CD59/membrane attack complex inhibitory factor
      (MACIF) in patients with paroxysmal nocturnal haemoglobinuria (PNH) and other
      haematological diseases. Flow cytometry showed that all 59 PNH patients had two
      or three erythrocyte populations, while all 74 patients with other haematological
      diseases and all 31 healthy volunteers had a single erythrocyte population. We
      compared the percentage of PNH III erythrocytes in the lysis test with the
      percentage of negative cells shown by flow cytometry in 52 PNH patients, and
      found a significant correlation (r = 0.960, P < 0.001). However, in 13 patients
      the erythrocyte phenotypes did not correspond in both tests. This was generally
      related to difficulty of detecting PNH II erythrocytes in the lysis test. In the
      PNH patients the ranges of mean fluorescence intensity for the negative,
      intermediate and positive erythrocyte populations were respectively 1.1-2.5, 2.2
      29, and 61-600 for CD59/MACIF positivity and 1.9-7.2, 3.6-22. and 31-350 for DAF
      positivity. In contrast, the mean intensities in healthy volunteers ranged from
      190 to 720 for CD59/MACIF and from 150 to 350 for DAF. These findings suggest
      that PNH can be diagnosed and phenotypic analysis of PNH erythrocytes can be
      performed by respectively assessing the fluorescence profiles and mean
      fluorescence intensities of both proteins using flow cytometry. Flow cytometry
      may provide a superior diagnostic method to the traditional tests for PNH.

PMID- 7506571
TI  - Mediastinal mass with fever and night sweats in a young farmer--potential
      pitfalls in the diagnostic work-up and treatment.

PMID- 7506572
TI  - Induction of T cells specific for the mutated segment of oncogenic P21ras protein
      by immunization in vivo with the oncogenic protein.
AB  - Many malignancies harbor mutated ras proto-oncogenes encoding 21 kDa proteins
      with single amino acid substitutions. Previous studies have shown that the
      aberrant p21ras proteins are potential tumor-specific antigens in that CD4+ class
      II major histocompatibility complex-restricted T cells specific for the mutated
      segment of various oncogenic p21ras proteins can be elicited by immunization in
      vivo with synthetic peptides corresponding to the mutated segment. T-cell
      recognition of an antigenic peptide within a protein may be influenced
      substantially, either positively or negatively, by flanking amino acid sequences
      as well as by more distal immunogenic or tolerogenic epitopes within the same
      protein. This study examined whether T cells specific for the mutated segment of
      an oncogenic p21ras protein can be elicited by immunization in vivo with the
      protein. The results showed that p21ras protein bearing the transforming single
      amino acid substitution of leucine for glutamine at residue 61 could elicit T
      cells specifically reactive to the mutated region of the protein in C3H/HeN mice.
      Thus, an abnormal p21ras protein specifically associated with malignant
      transformation can be immunogenic in vivo. These results predict that in some
      circumstances, mutated p21ras proteins expressed by malignancies might elicit
      detectable mutation-specific T-cell responses.

PMID- 7506573
TI  - Human leukocyte antigen-A2.1 restricted candidate cytotoxic T lymphocyte epitopes
      of human papillomavirus type 16 E6 and E7 proteins identified by using the
      processing-defective human cell line T2.
AB  - Human papillomavirus type 16 (HPV-16) is strongly associated with cervical
      cancer. HPV-16 cytotoxic T lymphocyte (CTL) epitopes may be good candidates for
      the development of an antitumor peptide vaccine. A set of 240 overlapping
      peptides nine amino acids in length with an eight amino acid overlap covering the
      entire sequence of the two viral oncogenes E6 and E7 was synthesized and tested
      for its ability to bind to the most common human leukocyte antigen class I
      molecule HLA-A2.1. Binding was measured with the human processing defective cell
      line T2, which expresses high numbers of empty HLA-A2.1 molecules that are
      unstable at 37 degrees C. These empty molecules can be stabilized by exogenously
      added peptides, and the extent of stabilization, measured by cell surface HLA
      A2.1-specific staining, can be taken as a measure of the relative HLA-A2.1
      binding affinity. Following this analysis, several HLA-A2.1 binding peptides were
      pinpointed. Preliminary data suggest that at least one of the high-affinity
      binding peptides identified is immunogenic even in an in vitro priming protocol,
      underlining the feasibility of the method described here to identify the
      immunogenic peptides and potential candidates for CTL peptide-based vaccines.

PMID- 7506574
TI  - Characterization of cytotoxic T lymphocyte epitopes of a self-protein, p53, and a
      non-self-protein, influenza matrix: relationship between major histocompatibility
      complex peptide binding affinity and immune responsiveness to peptides.
AB  - We previously described a motif prediction of major histocompatibility complex
      allele-specific peptides and an in vitro assay for actual measurement of peptide
      binding to human leukocyte antigen HLA-A2.1 molecules. Using this method we have
      identified candidate cytotoxic T lymphocyte (CTL) epitopes derived from a non
      self-protein (influenza matrix) and self-protein (p53). We now show that results
      of binding assays performed over a range of peptide concentrations indicate that
      distinct differences in HLA-A2.1 peptide binding affinities exist between the
      influenza matrix and p53 protein. The results for the influenza matrix protein
      indicate that the peptide that shows the highest binding affinity to HLA-A2.1 is
      identical to the known immunodominant peptide recognized by influenza virus
      specific CTLs. The results for p53 indicate that one of the peptides with a low
      binding affinity is capable of inducing specific CTL responses, but CTLs
      recognizing the highest affinity binding peptides were not obtained. These
      findings are discussed in terms of the distinct implications for induction of
      cellular immune responses directed against peptides with different binding
      affinities for HLA-A2.1 of proteins that constitute attractive targets for tumor
      immunotherapy.

PMID- 7506575
TI  - Recombinant vaccinia mucin vector: in vitro analysis of expression of tumor
      associated epitopes for antibody and human cytotoxic T-cell recognition.
AB  - We have constructed a recombinant vaccinia virus vector that contains human mucin
      MUC-1 cDNA. Analysis of the recombinant virus isolates showed the tendency of the
      vaccinia to delete large portions of the mucin tandem repeat region. Epstein-Barr
      virus (EBV)-immortalized B cell lines from humans and chimpanzees were infected
      and analyzed for expression of the mucin on the cell surface and the presence of
      specific epitopes in the tandem repeat region previously shown to be
      preferentially expressed on tumor cells and recognized by tumor-specific mouse
      monoclonal antibodies and human cytotoxic T lymphocytes (CTL). We found that this
      recombinant vector encodes expression of mucin that contains all the epitopes
      recognized by the antibodies. The tumor-specific epitopes can be further exposed
      by inhibition of O-linked glycosylation in infected cells. Lack of multiple
      tandem repeats, however, prevents major histocompatibility complex (MHC)
      unrestricted recognition by the CTL of the majority of infected cell lines.
      Still, we show two examples of an apparent MHC-restricted recognition of vaccinia
      encoded mucin that may depend on one or very few rare human lymphocyte antigen
      (HLA) types capable of presenting the mucin peptides.

PMID- 7506576
TI  - Identification of T-cell epitopes: rapid isolation of class I-presented peptides
      from viable cells by mild acid elution.
AB  - A novel method was developed to isolate immunogenic peptides (CD8+ T-cell
      epitopes) from class I complexes expressed at the cell surface of viable cells.
      Cells treated at pH 3.3 with citrate-phosphate buffer for periods as short as 15
      s remained viable and became phenotypically class I deficient. Qualitative loss
      of class I determinants was verified both serologically and by the incapacity of
      acid-treated cells to be lysed by class I-restricted cytolytic T lymphocytes
      (CTLs) in contrast to non-acid-treated controls. Flow cytometric analysis of acid
      treated cells suggests that class I heavy chains remain associated with the cell
      membrane, while the class I light chain (beta 2-microglobulin) is absent. Since
      the physical dissociation of beta 2-microglobulin from class I heavy chain is
      correlated with the release of previously class I-bound peptides, we examined
      acid-eluted cell-free supernatants for the presence of immunogenic peptides.
      Peptides were acid eluted from an influenza A strain-infected, HLA-A2+ cell line
      and were subsequently fractionated by reverse-phase high performance liquid
      chromatography (RP-HPLC). These fractionated peptides were examined for their
      capacity to sensitize an HLA-A2+ B cell line to lysis mediated by an influenza A
      matrix peptide- (Flu M1 57-68) specific, HLA-A2-restricted CTL line. A single
      peak of biologic activity was identified in HPLC fractions 47 and 48 derived from
      influenza-infected cells. These fractions contained a peptide of M(r) 968 with a
      sequence similar to the Flu M1 58-66 sequence GILGFVFTL. The application of this
      technique to other T-cell-based systems may aid in the definition of peptide
      epitopes relevant to viral, autoimmune, or neoplastic disorders.

PMID- 7506578
TI  - The coronary artery--from geometry to RNA turnover.
AB  - This review compares the geometry of conduit coronary arteries in man and
      animals, namely the wall/diameter ratio (1:7.4 and 1:15 respectively). The left
      and right ventricle volume determines the geometry (segment length and diameter)
      of both branches of the left coronary artery: ramus interventricularis anterior
      and ramus circumflexus; the range of deformation of the latter was substantially
      smaller. The heterogeneity of deformation was also found along the ramus
      interventricularis anterior, the deformation decreasing towards the apex. The
      above relations have consequences (i) on the haemodynamics (passive changes in
      conduit segment resistance), (ii) the deformation of coronary arteries triggers
      metabolic processes in the coronary wall. Four hours' lasting cardiac volume or
      pressure overload brought about an increase in the RNA content not only in the
      myocardium, but also in the coronary artery. The process is reversible. Moreover,
      the range of the RNA increase is in full concert with the heterogeneous
      deformability of the respective segment of the coronary tree.

PMID- 7506577
TI  - T-cell reconstitution by molecular, phenotypic, and functional analysis in the
      thymus, bone marrow, spleen, and blood following split-dose polychemotherapy and
      therapeutic activity for metastatic breast cancer in mice.
AB  - We examined the effect of a maximum tolerated, split-dose chemotherapy protocol
      of cyclophosphamide, cisplatin, and 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)
      on neutrophil and lymphocyte subpopulations in the peripheral blood leukocytes
      (PBLs), thymus, bone marrow, and spleen. It was found that this protocol of
      polychemotherapy, modeled after the induction protocol used with autologous bone
      marrow transplantation (AuBMT) for breast cancer, suppressed both B- and T-cell
      populations and T-cell function at times when the absolute neutrophil count had
      returned to normal or supernormal numbers. We observed an organ- and phenotype
      specific T- and B-cell recovery to normal levels following chemotherapy. However,
      despite normalization of cellularity and phenotype frequency, splenic lymphocytes
      remained unable to respond to normally concanavalin A (ConA). This
      polychemotherapy protocol in mice with an extensive experimental metastasis
      mammary tumor burden, was a dose lethal to 20% of the test group, which could be
      overcome with treatment by BMT and rHu interleukin (IL)-7. Furthermore, therapy
      with the T-cell augmenting agent rHu IL-7 had additive therapeutic activity and
      significantly prolonged survival beyond that of chemotherapy and BMT although it
      did not cure any mice with a heavy tumor burden. In summary, these studies
      demonstrate an organ-specific and selective polymorphonuclear neutrophil and T-
      and B-cell reconstitution following multidrug, split-dose chemotherapy on tissue
      and PBL populations, and a chronic depression in T-cell function, which when
      modified can result in significant therapeutic activity.

PMID- 7506579
TI  - Increased viral titer through concentration of viral harvests from retroviral
      packaging lines.
AB  - Dependent on the viral vector and the specific assay used, viral titers produced
      from commonly used retroviral packaging cell lines have an upper limit in the
      range of 10(5) to 10(7) infectious units/ml. We have developed a generally
      applicable method, using hollow-fiber filtration technology, which allows for the
      concentration of infectious virus derived from packaging lines. This method
      resulted in a reproducible 10- to 30-fold increase in viral titer and can readily
      be scaled to accommodate larger input volumes. Over 80% of the input virus is
      recovered in an infectious form in the concentrate. Concentrated virus containing
      media was seen to produce higher infection frequencies in Jurkat T cells as
      compared to unconcentrated virus containing media; however, this was not
      proportional to the differences in viral titer observed by limiting dilution
      analysis on NIH-3T3 cells. These results are discussed in relation to the
      importance of factors other than viral titer in determining transduction
      frequencies.

PMID- 7506580
TI  - Hematopoietic recovery following high-dose combined alkylating-agent chemotherapy
      and autologous bone marrow support in patients in phase-I clinical trials of
      colony-stimulating factors: G-CSF, GM-CSF, IL-1, IL-2, M-CSF.
AB  - Hematopoietic recovery in 115 patients with metastatic breast cancer or
      metastatic melanoma, enrolled in phase-I studies of recombinant growth factors
      while undergoing treatment with high-dose chemotherapy with autologous bone
      marrow support, was examined with assays of bone marrow progenitor cells and
      peripheral blood progenitor cells, and by evaluation of peripheral blood counts.
      Groups of patients receiving hematopoietic cytokine support [with interleukin-1
      (IL-1), interleukin-2 (IL-2), granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage CSF (GM-CSF), or monocyte CSF (M-CSF)] post marrow
      infusion were compared with contemporaneous control patients not receiving growth
      factor support. Patients receiving GM-CSF demonstrated statistically significant
      increases in the growth of granulocyte/macrophage colony-forming units (CFU-GM)
      in the bone marrow and peripheral blood compared with control patients. The
      effect of GM-CSF was dose dependent in the early period post marrow infusion (day
      +6) with bone marrow CFU-GM colonies at doses 8-16 micrograms/kg/day 34 times
      those measured in controls. Significant increases in bone marrow multipotential
      progenitor cells (CFU-GEMM) were seen in patients receiving GM-CSF day +21 post
      marrow infusion. Patients receiving IL-1 demonstrated significant increases in
      bone marrow CFU-GM at day +21, maximal at dosages of 24-32 ng/kg/day. There were
      no significant increases in burst forming unit-erythroid (BFU-E) among any study
      group. Patients receiving G-CSF had significantly increased absolute neutrophil
      counts (ANC) and total white blood cell counts (WBC) by day +11 post transplant
      compared with control patients. Patients receiving GM-CSF demonstrated
      significantly increased WBC (greater than 2000/mm3) at day +11 and ANC greater
      than 500/mm3 at day +16. Optimal dose of G-CSF and GM-CSF to stimulate neutrophil
      recovery post transplant was 4-8 micrograms/kg/day and 8-16 micrograms/kg/day,
      respectively. Platelet recovery did not differ among the six study groups. These
      data demonstrate accelerated myeloid recovery after high-dose chemotherapy and
      autologous bone marrow support in patients receiving either G-CSF or GM-CSF.
      Moreover, GM-CSF and IL-1 stimulate myelopoiesis at the level of bone marrow CFU
      GM, while G-CSF causes earlier neutrophil recovery peripherally.

PMID- 7506583
TI  - Short report: effect of sucralfate on angiogenesis in granulation tissue of
      acetic acid-induced gastric ulcers in rats.
AB  - We investigated the effect of sucralfate on angiogenesis in granulation tissue of
      gastric ulcers induced by acetic acid in rats using the carmine dye method.
      Intragastric administration of sucralfate at a dose of 500 mg/kg twice daily for
      9 days significantly accelerated ulcer healing and significantly increased the
      extent of angiogenesis in the ulcer base on the tenth day after ulcer induction.
      As we reported previously, intragastric administration of cimetidine at a dose of
      100 mg/kg once daily for 9 days decreased the extent of angiogenesis on the tenth
      day. However, combination treatment using sucralfate and cimetidine accelerated
      ulcer healing significantly, without altering the extent of angiogenesis. It is
      concluded, therefore, that the treatment with sucralfate may be effective in
      peptic ulcer disease from the standpoint of angiogenesis in the ulcer base.

PMID- 7506581
TI  - Growth factors controlling interleukin-4 action on hematopoietic progenitors.
AB  - We investigated the effect of interleukin-4 (IL-4) on human hematopoietic
      progenitors using low-density bone marrow cells from 29 hematologically normal
      donors. We found that IL-4 could either inhibit or stimulate cell growth,
      depending upon the other constituents of the culture medium. At concentrations
      ranging from 0.1 to 10.0 micrograms/ml, it significantly inhibited colony-forming
      units granulocyte-macrophage (CFU-GM) in the presence of either fetal calf serum
      alone, erythropoietin, leukocyte-conditioned medium prepared with
      phytohemagglutinin, granulocyte-macrophage colony-stimulating factor (GM-CSF),
      interleukin-3 (IL-3), or stem cell factor (SCF), in a dose-dependent fashion. In
      contrast, IL-4 stimulated CFU-GM colony multiplication in the presence of
      granulocyte colony-stimulating factor (G-CSF). Similar but less significant
      inhibitory effects were exerted by IL-4 on burst-forming units-erythroid (BFU-E).
      The growth-suppressive effect of IL-4 was partially reversed by IL-1 beta, and to
      a lesser extent by IL-6. When tested by enzyme-linked immunosorbent assay
      (ELISA), IL-4 suppressed cellular IL-1 beta production, and, similar to IL-4,
      anti-IL-1 beta-neutralizing antibodies inhibited CFU-GM colony growth, suggesting
      that the inhibition of endogenous IL-1 beta is a factor in regulating the IL-4
      effect. Furthermore, in the absence of exogenous growth factors, IL-4 inhibited
      CFU-GM colony growth when anti-G-CSF neutralizing antibodies were also present.
      Therefore, we tested the effect of IL-4 on G-CSF receptors and found that 6- or
      24-h incubation of low-density marrow cells with 1.0 microgram/ml IL-4 resulted
      in up-regulation of G-CSF receptors. Taken together, these results suggest that
      IL-4 possesses a dual modulatory role in the hematopoietic system via interaction
      with various cytokines.

PMID- 7506582
TI  - Hypergranular acute lymphoblastic leukemia (ALL). Report of a case and review of
      the literature.
AB  - We report a case of adult acute lymphoblastic leukemia (ALL) with myeloid-like
      hypergranulation of blast cells. Like most of the "granular" ALLs described in
      the literature, the blast cells had L2 morphology and exhibited a common-ALL
      immunologic phenotype. The clinical findings at diagnosis were unremarkable.
      Cytogenetic analysis showed a 46XY karyotype. Molecular genetic analysis revealed
      T-cell receptor (TCR) gamma and immunoglobulin heavy chain rearrangements; no
      rearrangement was found at the TCR beta gene locus. The polymerase chain reaction
      (PCR) for the BCR-ABL translocation was negative. The clinical course of the
      patient was uncomplicated. On standard ALL treatment protocol he achieved
      complete remission (CR) within 4 weeks, and he is currently disease free 8 months
      after diagnosis. The case contributes well-documented data to the
      characterization of adult "granular" ALL, with special regard to changes at the
      molecular genetic level.

PMID- 7506584
TI  - Factors useful in predicting the response to interferon therapy in chronic
      hepatitis C.
AB  - To determine how various factors influence the response to interferon (IFN)
      therapy, we retrospectively studied 157 consecutive Japanese patients with
      chronic hepatitis C who received various treatment schedules of IFN. They were
      divided into two groups on the bases of outcome. One group was comprised of 65
      patients who achieved a sustained normalization of serum alanine aminotransferase
      (ALT) levels for at least 6 months after treatment, while the other group was
      comprised of 84 patients with persistent elevation of serum ALT levels, despite
      treatment. Genotyping of hepatitis C virus (HCV) was done by polymerase chain
      reaction (PCR) with genotype specific primers, analysing the variations in
      nucleotide sequence within the NS 5 region of the HCV genome, namely genotypes
      PT, K1, K2a and K2b. We then used a multivariate analysis to determine the
      factors related to mode of treatment, patient characteristics and HCV genotype in
      relation to the response to IFN therapy. Of the 16 factors analysed, the HCV
      genotype (genotype K2a or K2b, P < 0.0008), treatment schedule (intermittent
      administration following a daily schedule, designated as combined schedule, P >
      0.0014) and liver histology just before treatment (chronic persistent hepatitis
      or mild chronic aggressive hepatitis, P < 0.0324) were the most strongly
      correlated with a normalizing response to IFN therapy. These results suggest that
      not only are the IFN treatment schedule and patient profile significant, but the
      properties of the virus also influences the response. However, as the IFN
      treatment schedule is the only changeable factor, it should be designed to
      maximize the benefit of IFN therapy.

PMID- 7506585
TI  - Low prevalences of HBV and HCV infection in patients with primary biliary
      cirrhosis in Taiwan: a case control study.
AB  - To study the role of hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infection in patients with primary biliary cirrhosis (PBC) against the background
      of HBV and HCV infection in the general population, serum specimens from a
      consecutive series of 27 patients with PBC and 108 age/sex matched 'healthy
      subjects' as control group were submitted to assays for hepatitis B surface
      antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to
      hepatitis B surface antigen (anti-HBs) and antibodies to hepatitis C virus (anti
      HCV). None of the patients with PBC were HBsAg or anti-HCV positive while 17
      (15.7%) and 6 (5.6%) of 'healthy' controls were HBsAg positive and anti-HCV
      positive (P = 0.017 and 0.26). Patients with PBC also had a significantly lower
      prevalence of HBV infection than matched controls (70.4% vs 88.9%, P = 0.022).
      The results suggest that neither HBV nor HCV plays any significant role in the
      pathogenesis of PBC, and that PBC would not develop or be masked in patients with
      HBV or HCV infection.

PMID- 7506586
TI  - Neuronal nitric oxide in the gut.
AB  - Motility of the gastrointestinal tract is directly controlled by enteric
      inhibitory and excitatory motor neurons that innervate the layers of smooth
      muscle. Inhibitory motor neurons mediate receptive and accommodative relaxations
      and control the opening of sphincters, thus playing an important role in normal
      gut motility. Recent studies have demonstrated that nitric oxide (NO) is an
      important neurotransmitter released by inhibitory motor neurons in animal and
      human gut. Antagonists of nitric oxide synthase (NOS), the synthetic enzyme for
      NO, reduce the effectiveness of transmission from inhibitory motor neurons.
      Exogenous NO mimics inhibitory nerve activation, and a variety of compounds that
      affect the availability of endogenously produced NO modulate relaxations of
      gastrointestinal smooth muscle. It is clear, however, that NO is unlikely to be
      the only transmitter released by enteric inhibitory motor neurons: several other
      substances such as vasoactive intestinal polypeptide (VIP), or related peptides,
      and adenosine triphosphate (ATP) are also likely to contribute to nerve-mediated
      inhibition. The identification of NO as a major inhibitory neurotransmitter to
      gastrointestinal smooth muscle fills an important gap in our understanding of the
      physiological control of motility and opens up a wide range of new experimental
      possibilities. It may eventually lead to the development of new drugs for
      motility disorders. It should be noted, however, that NO is important in the
      brain, in cardiovascular control, in blood cell function and in many other organ
      systems, suggesting that it may be difficult to achieve specific pharmacological
      intervention targeted on inhibitory neurotransmission in the gut, without
      undesirable side effects.

PMID- 7506587
TI  - Non-selective cation channel in bullfrog taste cell membrane.
AB  - Using single channel recordings of the patch clamp method, we found first that
      cation channels were present in the bullfrog taste cell membranes. These channels
      were widely distributed over the taste cell membrane. The conductance examined
      with inside-out patches was 30.7 +/- 5.7 pS (mean +/- S.D., n = 13). The
      permeability ratio of the cation channel to monovalent cations was PK:PCS:PNa =
      1.18:1.00:0.70, indicating that the channels are non-selective.

PMID- 7506588
TI  - A microdialysis study on striatal dopamine, 5-HT and metabolites in conscious
      rats after various treatments: evidence for extravesicular release of dopamine.
AB  - The effects of death and various treatments that affect the status of
      nigrostriatal neurones on striatal release of dopamine (DA) and 5
      hydroxytryptamine (5-HT) and their metabolites 3,4-dihydroxyphenylacetic acid
      (DOPAC), 3-methoxy-4-hydroxyphenylethylamine (3-MT), homovanillic acid (HVA) and
      5-hydroxyindoleacetic acid (5-HIAA) were studied by in vivo microdialysis. In
      conscious rats, DA and 5-HT levels were very low compared with their metabolites
      except 3-MT which was rarely detectable. Upon death by pentobarbitone overdose,
      there was an immediate surge of the DA level reflecting massive release of the
      neurotransmitter. This increase was accompanied by a significant increase in 3-MT
      level but not the other two DA metabolites. Post mortem release of 5-HT was also
      observed but to a much smaller extent than that of DA. The amounts of amines
      released appeared to be proportional to the amine stores. When L
      dihydroxyphenylalanine (DOPA) was administered to reserpinized rats, the
      extracellular levels of both DOPAC and HVA increased but not that of DA. However,
      marked release of DA occurred at death in contrast to reserpinized rats not
      injected with the precursor. It is evident that exogenous L-DOPA is taken up into
      the dopaminergic nerve endings and is converted to releasable extravesicular DA,
      and that this releasable DA is released, at least in part, in accordance with
      neuronal activities.

PMID- 7506589
TI  - Chronic morphine impairs axoplasmic transport in the rat mesolimbic dopamine
      system.
AB  - Chronic morphine has been shown to decrease levels of neurofilaments (NFs) in the
      ventral tegmental area (VTA), which plays a critical role in the rewarding
      properties of morphine and other drugs of abuse. Since decreased levels of NFs
      are closely associated with a decrease in slow axonal transport, we studied the
      effect of chronic morphine on axonal transport in the VTA-nucleus accumbens (NAc)
      pathway. Chronic morphine decreased axonal transport from the VTA to the NAc by
      50%. Chronic morphine did not alter axonal transport from the locus coeruleus to
      several of its projection areas, consistent with the lack of effect of chronic
      morphine on NFs in this brain region.

PMID- 7506590
TI  - NMDA receptors increase OH radicals in vivo by using nitric oxide synthase and
      protein kinase C.
AB  - Prolonged activation of brain N-methyl-D-aspartic acid (NMDA) receptors increases
      intraneuronal (Ca2+) and nitric oxide (NO) synthesis, and may be responsible for
      neuronal death in acute brain insults and chronic neurodegenerative diseases. NO
      can be converted in vitro to toxic hydroxyl (OH) radical. Using microdialysis of
      striatum in awake animals, we found that local NMDA receptor activation increased
      outflow of OH radicals four-fold. NMDA-stimulated OH production was blocked by
      inhibitors of nitric oxide synthase (NOS) and protein kinase C (PKC). NMDA
      receptor-mediated neuronal death may derive from NOS- and PKC-dependent synthesis
      of OH radicals.

PMID- 7506592
TI  - Selective loss of NADPH-diaphorase-containing neurons in the dentate gyrus
      following transient ischemia.
AB  - The effect of transient forebrain ischemia on NADPH-diaphorase-containing neurons
      was examined in the dentate gyrus of the gerbil. NADPH-diaphorase histochemistry
      was performed in animals subjected to temporary occlusion of the common carotid
      arteries and sham-operated animals. Seven days following transient ischemia, the
      number of NADPH-diaphorase-positive neurons in the infragranular zone of the
      dentate gyrus was reduced by approximately 50% compared with control animals.
      Since neighboring granule cells are known to be resistant to this level of
      ischemic challenge, the present observations indicate that NADPH-diaphorase
      containing neurons in the dentate gyrus are selectively vulnerable to brief
      ischemia.

PMID- 7506591
TI  - D1 agonists suppress zero Mg(2+)-induced epileptiform activity in the rat
      cingulate cortex slice.
AB  - This study determined whether dopamine can influence epileptiform activity in
      vitro through an action at D1 receptors. Dopamine (50-1000 microM) and the
      selective D1 agonists SKF 38393, SKF 75670, SKF 80723 and SKF 82526 (10-250
      microM) suppressed the paroxysmal discharges produced in rat cingulate cortex
      slices by the omission of Mg2+ from the bathing medium. These antiepileptic
      effects were mimicked by forskolin (10-100 microM), blocked by the D1 antagonist
      SCH 39166 (0.5 microM), facilitated by IBMX (500 microM) and unaffected by
      propranolol (2 microM), suggesting the participation of cyclic AMP in the D1
      response. Possible mechanisms, including direct postsynaptic inhibition,
      modulatory enhancement of GABA activity and presynaptic inhibition of glutamate
      release are considered.

PMID- 7506594
TI  - Matrix isolation applied to the 252Cf plasma-desorption mass spectrometry of
      underivatized oligosaccharides.
AB  - A number of different low molecular weight and volatile compounds have been
      tested and compared as matrices in 252Cf plasma-desorption mass spectrometry
      (PDMS) measurements of oligosaccharides. Some heteroaromatic amines (2
      aminothiazole and 3-aminopyridine), hydroxyanthraquinones (alizarin and
      quinalizarin) and phthaleins (fluorescein) proved to be especially suited to
      enhancing the quasimolecular ion intensity of oligosaccharides. Discrimination
      effects could be reduced by matrix addition and thus, quantitative results of
      PDMS could be improved. Oligosaccharides with broad molecular weight distribution
      (dextrin 10 and dextran T 1.5) have been successfully analyzed by PDMS. The mass
      spectra obtained compared quite well with ion chromatograms of the respective
      oligosaccharides.

PMID- 7506593
TI  - Binding of the AMPA receptor antagonist [3H]GYKI 53405 to Xenopus brain
      membranes.
AB  - GYKI 52466 and related 2,3-benzodiazepines are highly selective antagonists of
      AMPA-evoked responses in rat CNS. However, these compounds do not compete with
      [3H]AMPA binding and their site of action remains unclear. Here we show that
      [3H]GYKI 53405 binds specifically to Xenopus brain membranes with KD and Bmax
      values of 4.5 microM and 35 pmol mg-1 protein respectively. Binding is increased
      in the presence of Mg2+ and is unaffected by AMPA or kainate. This is the first
      report of the binding of a GYKI 52466-related radioligand to any tissue and these
      results provide an initial step towards the characterization of novel recognition
      sites which are of considerable therapeutic potential.

PMID- 7506595
TI  - Decentralization of the superior cervical ganglia inhibits mast cell mediated TNF
      alpha-dependent cytotoxicity. 1. Potential role of salivary glands.
AB  - Decentralization or ganglionectomy of the superior cervical ganglia (SCG) reduces
      pulmonary inflammation, as well as chemotaxis and activation of circulating
      neutrophils. However, the protective effect of decentralization was abolished
      when combined with removal of the submandibular glands (sialadenectomy) in the
      same animals. Thus, it has been postulated that the submandibular glands (SMG)
      release an anti-inflammatory factor(s) that is controlled by cervical sympathetic
      nerves. Decentralization of SCG did not modify in vitro histamine release or in
      vivo levels of rat mast cell protease II, but it reduced mast cell (MC)-mediated
      tumor necrosis factor alpha (TNF alpha)-dependent cytotoxicity. Combined
      decentralization/sialadenectomy abrogated the inhibition of MC cytotoxic
      activity, as we have shown previously for pulmonary inflammation and neutrophil
      functions. However, sialadenectomy alone inhibited MC-mediated TNF alpha
      dependent cytotoxicity, an observation which suggests that SMG produce a
      factor(s) that can potentiate MC cytotoxic activity. Studies of the effects of
      SMG-derived factors, such as epidermal growth factor, nerve growth factor, and
      transforming growth factor beta (TGF beta), showed that only pretreatment of MCs
      with TGF beta 10(-8) g/ml inhibited MC-mediated TNF alpha-dependent cytotoxicity.
      Thus, the modulation of MC-mediated TNF alpha-dependent cytotoxicity by cervical
      sympathetic innervation and SMG is complex and distinct from the modulation of
      pulmonary inflammation and neutrophil functions identified previously.

PMID- 7506596
TI  - Isolation of a sialic acid-specific surface haemagglutinin of Helicobacter pylori
      strain NCTC 11637.
AB  - A deionized water extract of Helicobacter pylori NCTC 11637 contained
      haemagglutinin activity that was (i) soluble (i.e., not associated with
      particulate material sedimented by centrifugation at 100,000 x g for 1 h), (ii)
      stable to lyophilization, (iii) heat-labile, (iv) chymotrypsin-sensitive, (v)
      inhibited by fetuin, orosomucoid, and NANLac, but not by asialofetuin and (vi)
      inactive against guinea pig erythrocytes incubated with Clostridium perfringens
      neuraminidase, but active against untreated guinea pig erythrocytes. The data
      support the idea that the haemagglutinin is a protein which recognizes the alpha
      (2-3) structure of sialylated glycoconjugates. Fractionation of the extract by
      isoelectric focusing and by gel filtration with Sephacryl S-400 indicated that
      the haemagglutinin has a pI of 3.7 and consist of high molecular-weight-protein
      aggregates. SDS-PAGE analysis of the preparation purified by gel filtration
      showed 3 protein bands at ca. 64 kD, 56 kD and 20 kD. Electron microscopy of H.
      pylori incubated with gold-labelled fetuin indicated that the haemagglutinin was
      associated with loosely adherent material on the bacterial surface, and that the
      purified haemagglutinin did not reveal a fimbrial structure. The ability to bind
      to sialoglycoconjugates on the erythrocyte membrane suggests that the
      haemagglutinin may be an important colonization factor enabling H. pylori to bind
      to similar saccharide structures on epithelial cells.

PMID- 7506597
TI  - Chemoembolization for hepatocellular carcinoma: epinephrine followed by a
      doxorubicin-ethiodized oil emulsion and gelatin sponge powder.
AB  - PURPOSE: This study evaluates chemoembolization (CE) of the liver with minimal
      vasoconstriction followed by selective intraarterial delivery of an emulsion of
      iopamidol, doxorubicin, and ethiodized oil and temporary occlusion of hepatic
      artery with gelatin sponge powder in patients with hepatocellular carcinoma.
      PATIENTS AND METHODS: Since 1988, 30 patients with nonresectable hepatocellular
      carcinoma underwent CE with the above protocol. Intraarterial epinephrine (0.5-1
      microgram diluted in 10 mL of saline) was rapidly injected directly into the
      proper hepatic artery or selectively into the right or left hepatic arteries and
      was followed by 40-60 mg of doxorubicin dissolved in 10 mL of iopamidol and
      emulsified in 20 mL of ethiodized oil. The chemoembolic mixture was injected at
      the rate of arterial flow. Liver function and clotting parameters were monitored
      three times a day until there was a downward trend toward preembolic levels.
      Computed tomography (CT) was performed immediately after embolization and at 1-3
      month intervals. Embolization was repeated when CT demonstrated recurrent or
      progressive disease. RESULTS: Disease recurred or progressed in 11 patients at 2
      17 months after embolization. CE was repeated in four patients; one individual
      underwent three embolizations. Re-embolization was performed up to 14 months
      after initial embolization (median, 10 months). Five patients (16.7%) died within
      1 month of embolization. Ten patients died at 3-33 months after CE. Two of these
      patients died of cirrhosis at 6 and 14 months, without evidence of recurrent
      tumor. Fifteen patients remain alive 5-28 months after CE. Kaplan-Meier
      estimation of probability of survival curves demonstrates a median survival of 14
      months. Sixty-one percent of patients were alive at 1 year and 36% at 2 years
      after the procedure. CONCLUSION: CE with use of the above technique is effective
      for palliating inoperable hepatocellular carcinoma. It causes a significant
      prolongation of survival over the expected 18-24 weeks in untreated patients;
      this may occur because high doses of chemotherapeutic agents are delivered and
      come in contact with the tumor for a longer period, followed by ischemia brought
      about by temporary arterial occlusion.

PMID- 7506598
TI  - Evolution of a CD3+CD4+ alpha/beta T-cell receptor+ mature T-cell clone from CD3
      CD7+ sorted human bone marrow cells.
AB  - In order to study extrathymic differentiation in vitro, CD7+CD3- lymphocytes were
      sorted from normal human bone marrow and cultured under conditions of limiting
      dilution together with irradiated pooled allogeneic peripheral blood mononuclear
      cells (PBMC) and phytohemagglutinin (PHA) in the presence of 1000 U/ml of
      interleukin-2 (IL-2). One clone was obtained that failed to react with monoclonal
      antibody (mAb) TCR delta 1 (TCR1, gamma/delta-specific) or WT31 (TCR2, alpha/beta
      specific). From day 35 through day 74 in culture, the surface phenotype of this
      clone evolved into CD3+, CD4+, CD8-, TCR2+, TCR1-, and was further characterized
      as CD2+, CD45RO+, CD16-, and CD56-. The presence of mRNA for TCR alpha and beta
      but not gamma and delta chains was confirmed by Northern blotting. Accessory cell
      dependent autocrine proliferative responses to PHA (most likely driven by IL-2)
      were initially absent, but became measurable at the same time as the TCR was
      acquired. However, in the absence of PHA, the clone failed to respond to a panel
      of homozygous B-cell lines representing the majority of MHC class II alleles.
      Autoreactivity was also not demonstrable. Cytotoxicity was limited to MHC
      unrestricted "natural killer (NK)-like" lysis of K562 target cells, with no
      autocytotoxicity detected. The NK-like lysis diminished over time in parallel
      with the acquisition of surface TCR. The cloned cells were not suppressive for
      mature lymphocyte proliferation. After stimulation, the cells secreted tumor
      necrosis factor alpha and granulocyte/macrophage colony-stimulating factor (GM
      CSF) detected by immunoassays, and T-cell growth factors, most likely IL-2, as
      detected by bioassays. Polymerase chain-reaction methods demonstrated the
      presence of mRNA for IL-2, IL-3, IL-4, IL-9, interferon-gamma, and GM-CSF in
      these cells after stimulation with PHA and B-LCL. These results suggest that
      cells with the phenotype and some functional characteristics of mature T
      lymphocytes can evolve extrathymically in vitro from T-cell precursors sorted
      from normal human bone marrow.

PMID- 7506599
TI  - Prenatal screening for trisomy 18 with free beta human chorionic gonadotrophin as
      a marker.
AB  - OBJECTIVE: To determine the relation between maternal serum alpha fetoprotein and
      free beta human chorionic gonadotrophin concentrations in pregnancies complicated
      by trisomy 18 and establish whether prenatal biochemical screening for this
      condition could be developed in a way similar to that proposed for trisomy 21.
      DESIGN: Serum alpha fetoprotein and free beta human chorionic gonadotrophin
      concentrations in women with singleton pregnancies affected by cytogenetically
      confirmed trisomy 18, uncomplicated by neural tube defect or ventral wall defect,
      were identified from prospective trisomy 21 screening programmes. Additionally,
      stored maternal serum from similar pregnancies was analysed retrospectively.
      Analyte concentrations from singleton unaffected pregnancies were identified from
      a prospective screening programme as controls. Statistical parameters of the
      affected and unaffected populations were compiled. SETTING: Biochemical screening
      laboratories in Britain and the United States. SUBJECTS: 52 women with singleton
      pregnancies complicated by trisomy 18; control population of 6661 women with
      unaffected singleton pregnancies. MAIN OUTCOME MEASURES: Median values of each
      analyte and their distribution in the affected and unaffected populations;
      detection rate of trisomy 18 and the false positive rate. RESULTS: Maternal serum
      alpha fetoprotein and free beta human chorionic gonadotrophin concentrations were
      significantly lower in pregnancies complicated by trisomy 18 (median values 0.71
      and 0.37 respectively). By using a multivariate risk algorithm incorporating
      maternal age risk of trisomy 18 and the concentration of the two biochemical
      markers it was predicted that 50% of trisomy 18 cases (unaffected by neural tube
      defect or ventral wall defect) could be detected with a 1% false positive rate.
      CONCLUSION: Second trimester biochemical screening for trisomy 18 could be a
      valuable addition to trisomy 21 screening programmes.

PMID- 7506600
TI  - Coaction of blue light and light absorbed by phytochrome in control of glutamine
      synthetase gene expression in Scots pine (Pinus sylvestris L.) seedlings.
AB  - The level of plastidic glutamine synthetase (GS; EC 6.3.1.2) in the cotyledonary
      whorl of the Scots pine (Pinus sylvestris L.) seedling was previously reported to
      be regulated by light. In the present paper we report on the control by light of
      the GS transcript level. A full-length GS cDNA clone of Scots pine was isolated
      (pGS1), sequenced and employed to measure GS transcript levels. Using dichromatic
      light treatments it was found that the transcript level is regulated by
      phytochrome. The strong specific effect of blue light is to be attributed to an
      increase of the responsiveness to phytochrome. Since no direct correlation
      between the transcript level and the rate of GS protein synthesis was observed,
      it was concluded that GS gene expression is only coarsely regulated at the level
      of transcript accumulation. Synthesis of GS protein is by itself light-dependent
      (light-mediated fine tuning of gene expression). This control at the
      translational level is also exerted via phytochrome with blue light determining
      the responsiveness of the process toward phytochrome. If the level of the far-red
      absorbing form of phytochrome (Pfr) is kept very low, blue light is not capable
      of bringing about synthesis of GS protein.

PMID- 7506601
TI  - A molecular inventory of human pancreatic islets: sequence analysis of 1000 cDNA
      clones.
AB  - The islets of Langerhans play a central role in glucose homeostasis by secreting
      the polypeptide hormones insulin and glucagon. They are comprised primarily of
      four endocrine cell types: insulin-secreting beta-cells which represent about 70%
      of the cells in the islet along with smaller number of cells secreting glucagon,
      somatostatin and pancreatic polypeptide. Diabetes mellitus results from the
      specific loss or dysfunction of the beta-cells. Because of the central role of
      the islets of Langerhans in the regulation of glucose homeostasis, we are
      preparing a database of genes expressed in this tissue. One thousand cDNA clones
      randomly isolated from a human pancreatic islet library were partially sequenced
      yielding 280 kilobases of sequence. Database searches indicated that 397 of the
      cDNAs represented known human genes or human homologs of genes identified in
      other species and a further 58 sequences corresponded to expressed sequence tags
      identified in other tissues or cells (contamination by exocrine pancreatic tissue
      was estimated to be less than 10%). 545 of the cDNAs were not related to any
      other sequences in the databases. The islet cDNA collection provides a unique
      source of genes for genetic studies of diabetes as well as for molecular studies
      of islet function in normal and diabetic states.

PMID- 7506602
TI  - Molecular basis of cystathionine beta-synthase deficiency in pyridoxine
      responsive and nonresponsive homocystinuria.
AB  - Cystathionine beta-synthase (CBS) deficiency is an autosomal recessive disorder
      associated with multisystem clinical disease. We analyzed PCR amplified products
      from patients' RNA and genomic DNA. Direct sequencing of the entire coding region
      of the CBS gene revealed a G-919 to A transition in exon 8, resulting in
      replacement of Gly 307 by Ser (G307S) in the protein. The mutation was detected
      in one allele of patient L171 of French/Scottish ancestry and in both alleles of
      patient L198 of Irish ancestry. Amplifying and sequencing exon 8 from the genomic
      DNA showed that both parents of L198 were heterozygotes for G307S. The
      pathogenicity of the mutation was demonstrated in an expression experiment. The
      mutant protein was apparently stable in E.coli extracts and lacked catalytic
      activity. Sequencing of exon 8 revealed the G307S mutation in five additional
      families. All patients have pyridoxine nonresponsive homocystinuria. We have now
      observed this mutation in 9 of 52 apparently unrelated alleles of varied ethnic
      backgrounds. All 9 are from patients with Celtic (Irish/English/Scottish/French)
      ancestry in either one or both parents. The G307S mutation was detected in 50% (9
      of 18) of the Celtic alleles in our series. The second mutation found in exon 8
      is the I278T mutation, which was described previously in one allele of a
      pyridoxine responsive patient. This missense mutation was detected in one allele
      of a pyridoxine nonresponsive patient and in both alleles of a pyridoxine
      responsive patient. The latter suggests that I278T is probably associated with
      pyridoxine responsiveness.

PMID- 7506604
TI  - Localisation of a gene for Darier's disease.

PMID- 7506603
TI  - Identification of human chromosome 9 specific genes using exon amplification.
AB  - We have recently developed a method, exon amplification, that is designed for
      isolation of exon sequences from genomic DNA. To assess the efficacy of this
      method we have analyzed cosmid genomic clones derived from human chromosome 9,
      and have cloned several products from this analysis. Approximately 63% of cosmids
      produced at least one product derived from functioning splice sites within the
      target genomic fragment, and in many cases multiple products were isolated. In
      addition, an easily identifiable class of false positives was produced from 56%
      of cosmids analyzed; these are readily eliminated from subsequent study. Sequence
      analysis and database searches revealed that the majority (87%) of the putative
      exon clones were unique, the remainder being derived from repetitive sequences.
      Analysis of sequence conservation by Southern blotting in addition to cDNA
      screening experiments suggested that most, if not all, of these unique sequences
      represent true exons. The results of these studies indicate that exon
      amplification is a rapid and reliable approach for isolation of exon sequences
      from mammalian genomic DNA.

PMID- 7506605
TI  - A donor splice mutation (405 + 1 G-->A) in cystic fibrosis associated with exon
      skipping in epithelial CFTR mRNA.

PMID- 7506606
TI  - A novel three-nucleotide deletion in the helix 2B region of keratin 14 in
      epidermolysis bullosa simplex: delta E375.

PMID- 7506607
TI  - Structure and regulation of tobacco extensin.
AB  - A tobacco cDNA clone (pCNT1) was characterized that encodes an extensin
      apoprotein almost entirely composed of the repeats Ser-Pro4(-Lys2), Pro-Tyr2-Pro2
      His and Thr-Pro-Val-Tyr-Lys. In healthy plants extensin transcripts are abundant
      in the roots, less prevalent in the stem and rare in the leaves. In leaves
      extensin mRNA is induced by wounding, ethylene or virus infection. Tobacco was
      transformed with pCNT1 cDNA coupled in sense or antisense orientation to the CaMV
      35S promoter. Analysis of transgenic plants that over- or underexpressed pCNT1
      mRNA demonstrated that the encoded protein constituted the majority of
      hydroxyproline-rich glycoproteins in roots, stems and leaves. The pCNT1-encoded
      protein contained at least 50% of total hydroxyproline present in these organs
      and was abundant in the soluble protein fraction of stems and roots as well as in
      the cell wall of stem vascular bundles. Analysis of transgenic plants expressing
      sense or antisense extensin gene constructs showed no correlation between total
      hydroxyproline concentration or soluble HRGP content and plant development.

PMID- 7506608
TI  - Wound performance.
AB  - The purpose of this study was to collect information about wound management
      practices which would establish baseline wound healing data. This data would be
      used to make measurable comparisons with new wound management techniques. This
      study focuses on data collected from the surgical area of Auckland Hospital. All
      patients whose wounds were surgically acquired were included in the study. Data
      collection was started immediately post-operatively and continued at each
      dressing change until the patient was discharged. The data collection tool was
      developed from "nursing expectations" of wound healing performance. This
      previously undefined set of expectations is an aggregate of the result of nursing
      knowledge, nursing experience and individual patients' conditions. The tool was
      refined against actual wound recovery and became a standard to test the accuracy
      of expectations. The wounds involved in this study were categorised and allocated
      expected healing rates. This was linked with discharge planning. It was against
      the stated range of expectations that wounds were measured for performance, as-
      "better than (expected)," "average," or "less than." Patients were divided into
      three broad age groups that reflected a particular health status and pre-existing
      influences. The groups chosen were: "20 years and under," "20 to 70 years" and
      "70 years plus." These groups were used as indicators to determine risk for wound
      management. Wound healing was measured as to whether it met nursing expectations.
      Factors such as wound appearance, complications, solutions and induction
      antibiotic cover were also measured. Findings show the hospital has a minimal
      level of complications of surgically acquired wounds.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7506609
TI  - [Treatment with methotrexate of 4 interstitial, unruptured pregnancies].
AB  - Successful treatment of four, non ruptured, cases of interstitial pregnancy are
      reported. Treatment consisted of in situ injection of methotrexate during
      coelioscopy. Dosage was 1.5 mg methotrexate per kilogram body weight. Negative
      plasma beta hCG levels were obtained 9 to 22 days after conservative medical
      treatment. No clinical or biochemical side effects were observed. Of two patients
      had no radiologically demonstrable cornual abnormality on the
      hysterosalpingographies effected at the 3 months evaluation after ascertained
      interstitial pregnancy, one have normal pregnancy. Two further patients had
      normal uneventful pregnancies 12 to 15 months later. Treatment of interstitial
      pregnancy by way of one in situ injection of methotrexate seems to be the
      currently preferred alternative to classical surgery.

PMID- 7506610
TI  - Choice and control. New opportunities for people with developmental disabilities.
AB  - Over the past few years, people with developmental disabilities have had an
      increasing number of opportunities to make choices and have control over their
      lives. There has also been a considerable amount of experimental research
      conducted on the effects of providing opportunities to make choices or to
      exercise control. The results of this research strongly suggest that providing
      opportunities for choice and control over events can affect the degree to which
      people participate in activities, the types of behaviors displayed during the
      participation, and people's perceptions about the situation. This article reviews
      this experimental research, discusses traditional views and current perspectives
      regarding choice and control for people with developmental disabilities, and
      presents ways of increasing the amount of choice and control available to people
      with developmental disabilities.

PMID- 7506611
TI  - Foodborne disease surveillance in England and Wales: 1989-1991.
AB  - This review summarises reports of food poisoning, salmonellosis,
      campylobacteriosis and other acute foodborne illness to the PHLS Communicable
      Disease Surveillance Centre, and notifications of food poisoning collated by the
      Office of Population Censuses and Surveys, in the period 1989-1991. During this
      period there were continuing rises in notifications of food poisoning and reports
      of salmonellosis and campylobacteriosis. There was considerable success in the
      control of foodborne listeriosis. Newly emerging pathogens, such as Vero
      cytotoxin producing Escherichia coli, became more important. There was
      unprecedented scrutiny of the salmonella data by experts and politicians,
      reflecting continuing concern over the role of eggs as well as poultry meat in
      the increase of Salmonella enteritidis phage type 4 infection. This concern,
      along with advances in information technology, has led to developments in the
      collection and dissemination of information which continue to be implemented.

PMID- 7506612
TI  - Small round structured viruses (SRSV).

PMID- 7506613
TI  - "Now is the time to act": World AIDS Day.

PMID- 7506614
TI  - Ring chromosome 15 involving deletion of the insulin-like growth factor 1
      receptor gene in a patient with features of Silver-Russell syndrome.
AB  - An 11-year-old girl with de novo r(15) (p12q26.3) with a clinical diagnosis of
      Silver-Russell syndrome (SRS) is presented. She had prenatal and postnatal growth
      deficiency with a severe short stature, peculiar facies characterized by a
      triangular face, a pinched nose with anteverted nostrils and down-turned corners
      of the mouth, bilateral clinodactyly of the fifth fingers, cafe-au-lait nevi,
      mental retardation, and a high level of serum follicular stimulating hormone.
      Southern blot analysis and chromosome fluorescence in situ hybridization revealed
      a deletion of the insulin-like growth factor 1 receptor gene (IGF1R) in the
      patient, the result indicating that IGF1R is assigned to 15q26.3. The deleted
      segment in our patient and comparisons with those of other reported cases of 15q
      suggest that one of the putative SRS loci is at 15q26.3.

PMID- 7506615
TI  - FGF-2 modulates dopamine and dopamine-related striatal transmitter systems in the
      intact and MPTP-lesioned mouse.
AB  - Following a previous study in which we showed ameliorative effects of basic
      fibroblast growth factor (FGF-2) locally applied to the nigrostriatal system in 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice, we investigated
      FGF-2 actions at different time intervals after the lesion and effects on non
      dopaminergic striatal transmitter systems. A triple intraperitoneal injection of
      30 mg/kg MPTP at 24 h intervals caused a reduction of striatal dopamine to 23% of
      control levels that lasted for at least 4 weeks. Four micrograms FGF-2 soaked
      into gel foam and placed onto the right striatum partially and bilaterally
      restored dopamine levels and tyrosine hydroxylase activity after 2 weeks, when
      the treatment started simultaneously or 1 day after the toxin lesion. FGF-2 was
      ineffective, if administration commenced with a delay of 7 days. Striatal
      neurotransmitters that are known to be linked to the dopaminergic system were
      also altered by the MPTP treatment. GABA was significantly increased, while
      somatostatin levels were reduced. Upon FGF-2 administration both GABA and
      somatostatin levels were partially normalized. Our data are consistent with the
      notion that FGF-2 protects and rescues acutely and subacutely MPTP-lesioned
      nigrostriatal neurons and that its effects must be mainly indirect. Likewise,
      positive effects of FGF-2 on non-dopaminergic neurons may be due to the partial
      restoration of striatal dopamine.

PMID- 7506617
TI  - Long-term depression requires nitric oxide and guanosine 3':5' cyclic
      monophosphate production in rat cerebellar Purkinje cells.
AB  - In patch-clamped Purkinje cells, bath application of the nitric oxide synthase
      inhibitor NG-methyl-L-arginine consistently prevents the induction of long-term
      depression (LTD) of parallel fibre-mediated excitatory postsynaptic potentials
      (EPSPs) induced by their pairing with calcium spikes. On the other hand, bath
      application of nitric oxide donors and of 8-bromoguanosine 3':5' cyclic
      monophosphate is able to reproduce an LTD-like phenomenon. LTD of parallel fibre
      mediated EPSPs also occurs when nitric oxide donors or guanosine 3':5' cyclic
      monophosphate are directly dialysed into Purkinje cells, and this effect
      partially occludes LTD induced by pairing protocols. These results show that
      nitric oxide does play a role in LTD induction, and demonstrate for the first
      time that its site of action is probably the soluble guanylate cyclase of
      Purkinje cells.

PMID- 7506616
TI  - Enhancement of AMPA-mediated synaptic transmission by the protein phosphatase
      inhibitor calyculin A in rat hippocampal slices.
AB  - Using the phosphatase inhibitor calyculin A, we have examined the influence of
      phosphorylation on synaptic transmission and plasticity in rat CA1 hippocampal
      slices. Bath application of 0.5-1 microM of calyculin A resulted in an increase
      of 42.6 +/- 2.9% in synaptic responses. The effect produced by calyculin A was
      not accompanied by changes in fibre volley, was not associated with changes in
      paired-pulse facilitation, and could be reproduced by intracellular injection of
      the compound, thereby indicating a postsynaptic action. Also, the synaptic
      enhancement produced by calyculin A was expressed only by potentials mediated by
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but not by
      the NMDA responses recorded in the presence of the AMPA receptor antagonist 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX) and low magnesium. The effect of
      calyculin A could be prevented by KN-62, an inhibitor of calcium/calmodulin
      dependent protein kinase II. Long-term potentiation could still be induced in the
      presence of calyculin A, but the effect of the compound was slightly reduced on
      potentiated compared with control pathways. These results indicate that calyculin
      A can selectively increase the efficacy of AMPA receptor-mediated synaptic
      transmission at excitatory synapses.

PMID- 7506618
TI  - Functional topography of the myelin-associated glycoprotein. I. Mapping of
      domains by electron microscopy.
AB  - The functional topography of the myelin-associated glycoprotein (MAG) was
      investigated by electron microscopic analysis of rotary-shadowed molecules of a
      MAG fragment (MAG 90) comprising the five immunoglobulin-like domains of the
      extracellular part of the molecule. MAG 90 molecules appeared as rod-like
      structures (18.5 +/- 1.2 nm long and 4.0 +/- 0.8 nm wide) with a globular domain
      at one end. Antibodies directed against the amino- and carboxy-terminus of MAG 90
      interacted with the non-globular terminal region, indicating that the molecule is
      bent in the globular region with the amino- and carboxy-terminal arms in close
      apposition to each other. An antibody which interferes with the binding of MAG to
      neurons interacted predominantly with the globular domain of MAG 90. The fibril
      forming collagen types I, III and V bound mainly to the non-globular terminal
      region of MAG 90, whereas the majority of heparin molecules interacted with the
      globular region of the molecule. The L2/HNK-1 carbohydrate structure was
      localized at the non-globular region in the protein fragment comprising the
      fourth and fifth immunoglobulin-like domains.

PMID- 7506619
TI  - Changes in DNA synthesis rate in the Schwann cell lineage in vivo are correlated
      with the precursor--Schwann cell transition and myelination.
AB  - During the development of the rat sciatic nerve extensive proliferation of glial
      cells occurs, and there is a very substantial rearrangement of the
      cytoarchitecture as axons and Schwann cells assume relationships which lead to
      the formation of the myelinated and unmyelinated axons characteristic of adult
      nerve. The maturation of Schwann cells from Schwann cell precursors and the
      matching of Schwann cell numbers to axons is an important part of this process.
      We have therefore studied the proliferation of Schwann cell precursors and
      Schwann cells during the development of the rat sciatic nerve from embryonic day
      14 to postnatal day 28 by combining bromodeoxyuridine injections of rats with
      double-label immunohistochemical techniques. The results reveal that DNA
      synthesis occurs in both Schwann cell precursors and Schwann cells throughout
      early nerve development. The labelling index is already substantial at embryonic
      day 14, but from embryonic day 17, when essentially all the glial cells have
      converted from precursor to Schwann cell phenotype, it rises sharply, peaking
      between embryonic day 19 and 20 before declining precipitously in the early
      postnatal period. This rapid decline in DNA synthesis coincides with the
      appearance of the myelin protein P0, and in individual cells DNA synthesis is
      incompatible with the expression of P0 protein. Nonmyelin-forming Schwann cells,
      which mature later in development, continue to synthesize DNA until at least
      postnatal day 15, but by day 28 essentially all Schwann cells in the nerve are
      quiescent.

PMID- 7506620
TI  - Two signal transduction mechanisms of substance P-induced depolarization in locus
      coeruleus neurons.
AB  - Effects of substance P on cultured neurons of the locus coeruleus of the rat were
      studied using the whole-cell patch clamp technique. In some cells substance P
      produced a decrease in a K conductance which showed an inwardly rectifying
      property. In other cells substance P produced an initial inward current which was
      accompanied by a conductance increase. The rest of the cells showed responses
      which were mixtures of the above two responses. The measurement of the reversal
      potential of the initial inward current after suppressing the voltage-gated Ca
      and K conductances suggests that it is caused by an increase in a non-selective
      ionic conductance. In cells loaded with 260 microM GTP gamma S, application of
      substance P produced an irreversible reduction of the K conductance, while the
      initial inward current could still be recorded, suggesting that the former is
      mediated by a G protein, whereas the latter may be activated by a different
      signal transduction mechanism. The initial inward current was not eliminated by
      external application of high concentrations of tetrodotoxin, d-tubocurarine or
      amiloride. Nor was it affected by the intracellular application of cyclic GMP or
      cyclic AMP.

PMID- 7506621
TI  - IgG4 blocking effect on the release of antigen-specific histamine.
AB  - We evaluated the biological effect of IgG4 antibodies in pollinosis. We studied
      the ability of IgG4 to mediate histamine release by measuring anti-IgG4 in
      pollinic patients without previous immunotherapy. We also evaluated the
      modifications that sera rich in specific IgG4 and IgG itself exert upon antigen
      specific histamine release. According to our results, stimulation with anti-IgG4
      did not induce histamine release, as opposed to stimulation with anti-IgE, which
      induced histamine release in all the cases studied. On the other hand,
      hyperimmune sera from pollinic subjects under immunotherapy and with high levels
      of specific IgG4 significantly inhibited the release of antigen-specific
      histamine from basophils of untreated patients. After isolating IgG4 by means of
      affinity chromatography, preincubation of this fraction with the allergen gave
      rise to a significant reduction in histamine release compared to preincubation of
      the antigen with normal sera.

PMID- 7506622
TI  - Influence of immunotherapy on histamine release and other immunological
      parameters of immediate hypersensitivity in pollinosis.
AB  - Specific immunotherapy in pollen-allergic patients leads to a significant time
      dependent decrease in the seasonal differences in IgE values, that is, the
      shorter the duration of immunotherapy, the smaller the difference. Immunotherapy
      leads to a maximum specific histamine release during the first year, with higher
      values during the pollen season. Later, the amount of histamine released from
      basophils decreases gradually in relation to the duration of immunotherapy and
      the clinical recovery, indicating that this would be a useful parameter in the
      follow-up of the efficacy of this type of treatment. Inversely, total histamine,
      which may be considered a parameter indicating the histamine stored in basophil
      granules, decreases significantly, reaching its lowest values at the end of the
      first year, with eventual recovery to initial values. From these results we may
      conclude that hyposensitizing treatment should not be interrupted before 3 years,
      since the immunological variations of the immediate hypersensitivity parameters
      take place during the first 2 years, and then stabilize. On the other hand, the
      correlation between the degree of recovery after hyposensitizing treatment and
      the duration of the treatment leads us to recommend immunotherapy for periods
      longer than 2 years.

PMID- 7506623
TI  - Construction and application of chromosomally integrated lac-lux gene markers to
      monitor the fate of a 2,4-dichlorophenoxyacetic acid-degrading bacterium in
      contaminated soils.
AB  - A reporter gene system, containing luxAB and lacZY, was constructed and
      integrated, using Tn7 transposition, into the chromosome of a 2,4
      dichlorophenoxyacetic acid (2,4-D)-degrading soil bacterium, Pseudomonas cepacia
      (BRI6001), to monitor its fate when introduced into soil microcosms. The genes
      were stably maintained in the modified strain of BRI6001, BRI6001L, for more than
      300 generations in the absence of selection pressure, and had no apparent effects
      on biochemical or physiological properties. BRI6001L was easily and rapidly
      identified as light-emitting blue colonies on 2,4-D medium containing XGal (5
      bromo-4-chloro-indolyl-beta-D-galacto-pyranoside) in the presence of n-decanal.
      Survival rates of BRI6001L introduced into non-sterile soil microcosms were
      substrate- and contaminant-dependent. The decrease in population density was
      lowest in a 2,4-D-amended agricultural soil, and highest in a wood-treatment
      facility soil contaminated with pentachlorophenol, creosote and heavy metals. A
      viable cell density as low as 10 cfu g-1 was detected in soil microcosms. The
      biochemical and growth properties of BRI6001 and BRI6001L, and their behaviour
      when introduced into soil microcosms indicates that BRI6001L can be used as a
      reliable model to predict the fate of BRI6001 when used to bioaugment
      contaminated soil.

PMID- 7506624
TI  - Prostatic surgery for benign prostatic hyperplasia: meeting the expanding demand.
AB  - We describe changes in the pattern of surgery for benign prostatic hyperplasia
      (BPH) in Scotland between 1971 and 1989. The data are based on an analysis of
      routinely collected Scottish hospital in-patient statistics for primary prostatic
      operations on men with a diagnosis of BPH (ICD Code 600.0). Primary operation age
      adjusted rates for BPH increased from 8.9 to 15.8 per 10,000 male population from
      1971 to 1989. This was accompanied by a reduction in bed day use for BPH surgery
      from 49,500 bed days in 1971 to 36,000 in 1989. Case fatality for all surgery for
      BPH also fell steadily and can no longer be regarded as a relevant measure of
      prostatectomy outcome. Virtually all surgical intervention is now transurethral
      resection (TUR), forming 94% of surgery for BPH in 1989 compared with only 32% in
      1971. The increase in surgical procedures carried out for BPH has been greater in
      younger age groups. If the pattern of increasing surgical intervention in the
      management of BPH over the past few years continues and there is an increased
      demand for treatment, and if the reported demographic changes occur, there will
      be a need for an additional 9 new consultant urologists in Scotland by 2001. Even
      if present operation rates hold steady, population changes alone will produce
      enough work for 2 more urologists.

PMID- 7506625
TI  - The source of organisms in the post-prostatectomy bacteriuria of patients with
      pre-operative sterile urine.
AB  - Ninety patients undergoing prostatectomy for benign prostatic hyperplasia (BPH)
      with sterile urine pre-operatively were prospectively studied for post
      prostatectomy bacteriuria; 26 of 90 patients (29%) developed bacteriuria (18 of
      64 after transurethral resection (TUR) and 8 of 26 after open prostatectomy), of
      whom 15 had pre-operative indwelling urethral catheters. The correlation of
      bacteriuria with several factors was studied, namely the presence of a
      histological inflammatory reaction within the prostatic adenoma, prostatic
      culture, intra-operative outgoing irrigation fluid culture, intra-operative blood
      culture and post-operative external meatal swab culture. The only significant
      correlation was between bacteriuria and meatal cultures. It was concluded that
      post-prostatectomy bacteriuria is probably caused by post-operative ascending
      infection along urethral catheters. There was not enough evidence to ascribe
      bacteriuria to pre-existing septic foci within the adenoma. Intra-operative
      contamination and infection from distant foci were also unlikely causes.

PMID- 7506626
TI  - Biphosphonates as an adjunct to palliative therapy of bone metastases from
      prostatic carcinoma. A pilot study on clodronate.
AB  - Clodronate (Ostac) is a specific inhibitor of osteolysis from the group of
      biphosphonates. The efficacy and side effects of palliative treatment with the
      substance were investigated in an open prospective non-controlled pilot study in
      41 patients with advanced, progressive, hormone-resistant prostatic carcinoma.
      All patients suffered from symptomatic bone metastases. Initially, they underwent
      an 8-day saturation course with 300 mg clodronate i.v. per day. A good to very
      good analgesic effect was achieved within 3 to 5 days in 29 patients (71%). The
      mean duration of action was 7 weeks and the mean survival time 12 weeks. There
      were no side effects after i.v. administration. Slight gastrointestinal
      discomfort was reported in 3 patients following oral administration. Delayed
      progression of the metastases was not observed. Clodronate is a promising
      addition to the other therapeutic possibilities in hormone-resistant prostatic
      carcinoma.

PMID- 7506627
TI  - Ultrasonic detection of non-palpable seminal vesicle invasion: a
      clinicopathological study.
AB  - In an effort to identify reliable criteria for detecting seminal vesicle invasion
      (SVI) with transrectal ultrasonography (TRUS) in patients with clinically
      localised prostate cancer, we reviewed the pre-operative sonograms in 230
      patients who underwent radical retropubic prostatectomy; 49 patients (21%) had
      pathologically confirmed SVI. Conventional sonographic criteria for SVI
      (asymmetry, distension, atrophy, abnormal echogenicity and irregularity in
      outline) were present in 58 patients, but only 16 (28%) had pathologically
      confirmed SVI. On the basis of the results of a preliminary comparison of radical
      prostatectomy specimens and TRUS, we had revised our criteria for the recognition
      of SVI: (1) a hypoechoic lesion at the base of the prostate (within 10 mm of the
      seminal vesicle); (2) an "adhesion sign" resulting from the loss of the echo
      reflections from the normal fat plane between the prostate and the seminal
      vesicle; (3) "posterior convexity" of the seminal vesicles. When we reviewed the
      230 sonograms retrospectively, we found a hypoechoic tumour at the base in 70
      patients, of whom 37 had SVI (positive predictive value (PPV) 53%). An adhesion
      sign was found in 16 patients, 12 of whom had SVI (PPV 75%). Posterior convexity
      was present in 4 patients, all of whom had SVI. If any one of our sonographic
      signs was present, the overall accuracy (83%), sensitivity (90%) and positive
      predictive value (51%) were significantly better than with any one of the
      conventional criteria. Patients with SVI were also more likely to have a high
      serum prostate specific antigen (PSA) level. The PPV for SVI of a PSA level > or
      = 10 ng/ml was 38%. If the PSA was > 10 ng/ml and TRUS was positive (> or = 1 of
      our sonographic criteria), 16 (62%) of 26 patients had SVI. If the PSA was < 10
      ng/ml and TRUS was negative, only 3 (3%) of 86 patients had SVI. It was concluded
      that the conventional criteria for detecting SVI on ultrasonography are not
      accurate in patients with early stage prostate cancer. There are, however,
      reliable criteria that predict SVI with reasonable accuracy and these criteria,
      combined with the serum PSA levels, can stratify patients into those with a low
      risk and those with a high risk of SVI.

PMID- 7506628
TI  - Comparative study of selective alpha 1-adrenoceptor blockade versus surgery in
      the treatment of prostatic obstruction.
AB  - Alternative treatments for benign prostatic hyperplasia (BPH) are the source of
      much discussion at present. Pharmacotherapy has been demonstrated to have an
      increasing role in the management of BPH. This study contrasts the efficacy of
      the selective alpha antagonist prazosin as compared with placebo and the
      subsequent improvements seen following surgical treatment. Whilst selective alpha
      blockade has undoubted therapeutic efficacy the improvement in symptom scores and
      the objective urodynamic measure of the flow rate are not as marked as those seen
      following surgery.

PMID- 7506629
TI  - Induction of cholinergic and adrenergic differentiation in N-18 cells by
      differentiation agents and DNA demethylating agents.
AB  - Effects of various differentiating agents and DNA demethylating agents on the
      expression of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH),
      marker enzymes for cholinergic and adrenergic differentiation, respectively, were
      examined in N-18 neuroblastoma cells. Retinoic acid (RA) and a medium conditioned
      over C6-glioma cells (GCM), which have been shown to enhance the ChAT activity of
      PC12 cells, NG108-15 cells and fetal rat brain cells, did not induce ChAT
      activity of N-18 cells. Treatment of the cells with the DNA demethylating agents
      alone also did not affect ChAT activity. But after pretreatment of the cells with
      the DNA demethylating agents, ChAT activity of N-18 cells was greatly increased
      by either RA or GCM. TH activity of N-18 cells was enhanced by forskolin, an
      activator of adenylate cyclase. The pretreatment of the cells with the DNA
      demethylating agents greatly enhanced the induction of TH activity by forskolin.
      Levels of ChAT and TH messenger RNA were altered in accordance with changes in
      ChAT and TH activities. Possible mechanisms of the actions of the demethylating
      agents on cholinergic and adrenergic differentiation are discussed.

PMID- 7506630
TI  - Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. IV.
      Evidence for the involvement of two signals.
AB  - Axonal regeneration over long distances is dependent upon events occurring both
      in the distal stump and in the neuronal cell body. Little is known concerning how
      events in the distal stump influence the cell body response to injury, or the
      axon reaction. In the present study, we examined this relationship for one
      component of the axon reaction (i.e. aberrant neurofilament (NF) phosphorylation)
      in the C57BL/Ola (Ola) mouse mutant, a model which exhibits delayed Wallerian
      degeneration (up to 3 weeks) and retarded regeneration of sensory neurons. Non
      axotomized normal (C57/6J/BL) and Ola mice demonstrated modest immunostaining to
      phosphorylated NF (pNF) epitopes (using monoclonal antibody 06-17) in some (11%)
      L4 dorsal root ganglion (DRG) neuronal cell bodies. In normal mice, modest to
      intense immunoreactivity was present in 43% of DRG neurons at 1 week following a
      sciatic nerve crush (axotomy). The intensity and extent of staining declined with
      reinnervation, being reduced slightly at 2 weeks and more notably by 3 weeks
      following axotomy. In Ola mice, the intensity and extent (43%) of staining were
      not different from normal axotomized mice at 1 week following axotomy. However,
      the intensity was less and the extent of staining reduced by 28% at 2 weeks
      following axotomy. By 3 weeks, staining levels were again increased, being
      similar to that observed in Ola and normal mice at 1 week following
      axotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506631
TI  - Involvement of noradrenergic and 5-hydroxytryptaminergic systems in allylnitrile
      induced head twitching.
AB  - Allylnitrile induces in rats persistent behavioral abnormalities, including head
      twitching, following a single administration. We studied the role of 5
      hydroxytryptamine (5-HT) and noradrenaline (NA) systems in the brain of rats in
      inducing and maintaining the head twitching. Allynitrile (1.49 mmol/kg) induced 5
      HT system activation in all areas of the brain studied 1-4 days after oral
      administration, and a reduction in the content of NA in the hippocampus, cortex
      and hypothalamus 1 day after dosing, in the hippocampus, cortex, hypothalamus and
      midbrain 2 days after dosing, and in the hypothalamus 4 days after dosing.
      Allylnitrile induced no change in the content of 5-HT, 5-hydroxyindoleacetic acid
      (5-HIAA) or NA 7-28 days after dosing. Pretreatment with 5,7-dihydroxytryptamine
      (5,7-DHT) suppressed the allylnitrile-induced head twitching, and decreased the
      contents of 5-HT and 5-HIAA in almost all areas of the brain throughout the
      observation period, as well as the ratio of 5-HIAA/5-HT in the medulla oblongata
      plus pons from 1 to 30 days after dosing with allylnitrile. No change in NA was
      observed in any areas of the brain. Pretreatment with N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP-4) increased the head twitching induced by allylnitrile,
      and decreased the content of NA in all areas of the brain throughout the
      observation period, without any change in the contents of 5-HT or 5-HIAA or in
      the ratio of 5-HIAA/5-HT. The present results suggest the involvement of 5-HT and
      NA systems in allylnitrile-induced head twitching.

PMID- 7506632
TI  - Prostaglandin E2 excites neurons of the nucleus tractus solitarius by activating
      cation channels.
AB  - Nucleus tractus solitarius (NTS) has a high density of prostaglandin E2 (PGE2)
      binding sites. Action of PGE2 (10(-9)-10(-6) M) was tested on neurons in a NTS
      slice with patch-clamp recording under synaptic blockade. PGE2 raised the firing
      rate in approximately half of the neurons in cell-attached patch mode. In whole
      cell current clamp, PGE2 depolarized membrane potential accompanied by an
      increase in firing rate. In whole-cell voltage clamp (-58 mV), PGE2 induced the
      inward current with an increase in conductance. The current was linearly related
      to voltage from -100 mV to -10 mV and suppressed between -10 mV and 20 mV. The
      current-voltage curve remained similar under low external Cl- or high internal Cl
      conditions and after external Na+ was replaced by Cs+. It is concluded that PGE2
      excites NTS neurons by activating cation conductance.

PMID- 7506633
TI  - Different functions of spinal 5-HT1A and 5-HT2 receptor subtypes in modulating
      behaviour induced by excitatory amino acid receptor agonists in mice.
AB  - The modulating effects of 5-HT1A and 5-HT2 receptor agonists on behaviour spinal
      excitatory amino acid (EAA) agonists were examined. Intrathecal (i.th.)
      administration of both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5
      methyl-4-isoxazole-propionic acid (AMPA) produce a behavioural syndrome of
      caudally directed biting and scratching. Serotonin (5-HT) agonists were
      coadministered with either NMDA or AMPA, and changes in EAA-induced behaviour
      were scored. All drugs were administered i.th. The 5-HT1A agonist 8-hydroxy-2-(di
      n-propylamino)tetralin hydrobromide (8-OH-DPAT) (15-60 nmol) reduced both NMDA
      (0.25 nmol) and AMPA (0.06 nmol) induced behaviour in a dose-dependent manner,
      and preadministration of the 5-HT1A receptor antagonist, 1-(2-methoxyphenyl)-4-[4
      (2-phthalimido)butyl]piperazine hydrobromide (NAN-190) (20 nmol) reversed this
      effect. The administration of the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane (DOI) (0.7-28 nmol) produced a dose-dependent behavioural syndrome
      similar to the EAA agonists. This was reversed by preadministration of ritanserin
      (10 nmol), a 5-HT2 antagonist. When DOI was coadministered with NMDA (0.25 nmol)
      or MAPA (0.06 nmol) there was an increase in the behaviour recorded and this
      effect was antagonised by ritanserin. The results of this study implicate that in
      the spinal cord subtypes of 5-HT receptors have different effects on modulation
      of behaviour induced by activation of the NMDA or the AMPA receptors; the
      activated 5-HT1A receptors have an inhibitory effect whereas activation of the 5
      HT2 receptors enhance the induced behaviour.

PMID- 7506634
TI  - Active specific immunotherapy against adenocarcinomas.

PMID- 7506635
TI  - Chromosome aberrations in CD34-positive acute myeloid leukemia. Correlation with
      clinicopathologic features.
AB  - Morphologic, immunologic, and cytogenetic features were studied in 30 newly
      diagnosed patients with CD34-positive (CD34+) de novo acute myeloid leukemia
      (AML) in comparison with 30 patients with CD34-negative (CD34-) AML. Karyotype at
      diagnosis was abnormal in 25/30 CD34+ AML patients, of which nine had major
      karyotype aberrations (MAKA). Clonal chromosome changes were detected in 9/30
      patients with CD34- AML. The most frequent chromosome aberration in CD34+
      patients was -5/5q-, an aberration showing a strong association with the M2 FAB
      subtype of AML. Other recurring chromosome changes involved chromosome 16q (four
      cases) and chromosome 17p (three cases). Total or partial monosomy 7q was
      detected in three cases. Among CD34- AML, two patients had the classical t(15;17)
      and two had structural aberrations of 6q. Among patients with CD34+ AML, nine had
      MAKA in association with trilineage myelodysplasia (TMDS). TMDS was infrequent in
      CD34+ AML without MAKA and in CD34- AML. Complete remission (CR) was achieved in
      8/30 CD34+ AML (26%), as compared with 22/30 CD34- AML (73%), and median survival
      was 2 months in the former group and 8 months in the latter. No patient with
      CD34+ AML and MAKA achieved CR, whereas 8/21 CD34+ AML without complex chromosome
      changes or with normal karyotype achieved CR. In conclusion, a distinct
      cytogenetic profile may be associated with CD34+ AML. Cytogenetic findings in
      CD34+ AML may be clinically relevant in that they may disclose a subset of
      patients with MAKA with a low CR rate.

PMID- 7506637
TI  - Acquired coronary angiogenesis after myocardial infarction.
AB  - Acquired coronary artery microvascular fistulas have been reported in only a few
      patients after myocardial infarction. We describe 1 patient in whom serial
      coronary angiography demonstrated the development of coronary angiogenesis at the
      site of an old myocardial infarction. The area of neovascularity was associated
      with a large apical left ventricular thrombus. This finding suggests that growth
      promoting mitogens are present in myocardium and thrombus and that angiogenesis
      occurs in some patients following myocardial infarction.

PMID- 7506636
TI  - Establishment of Epstein-Barr virus-associated lymphoma cell line SUBL with
      t(2;3)(p11;q27) from a liver transplant patient.
AB  - A new lymphoma cell line, designated SUBL, was established from a Japanese
      patient with Epstein-Barr virus (EBV)-associated lymphoma, which developed during
      FK 506 therapy after liver transplantation. This cell line has undergone 80
      passages over a period of 22 months. The cultured cells were positive for CD19,
      CD20, CD21, CD22, CD23, and HLA-DR, and negative for CD10 and surface
      immunoglobulins. Immunoglobulin gene analysis revealed rearrangements of JH and
      JK. T-cell antigens or T-cell receptor gene rearrangements were not observed on
      the cell line. The SUBL cells were positive for Epstein-Barr virus nuclear
      antigen (EBNA). The EBV genome was detected in the original tissue and the cell
      line by the in situ hybridization method. These data indicate that this cell line
      represents the B-cell lineage at a pre-B-cell stage. SUBL cells showed successful
      heterotransplantation to mice with severe combined immunodeficiency (SCID).
      Chromosomal analysis revealed the karyotype 46,XY,t(2;3)(p11;q27). Molecular
      studies showed that c-myc, N-myc, and bcl-2 were not rearranged. This cell line
      will provide a useful in vitro system to study the relationship between
      chromosomal abnormalities and the activation of cellular oncogenes.

PMID- 7506638
TI  - Effect of UCN-01, a selective inhibitor of protein kinase C, on the cell-cycle
      distribution of human epidermoid carcinoma, A431 cells.
AB  - UCN-01 (7-hydroxy-staurosporine), a selective inhibitor of protein kinase C
      (PKC), was shown to exhibit antitumor activity in murine and human tumor cell
      lines in vitro and in vivo. On the other hand, staurosporine, a non-selective
      protein kinase inhibitor, was not shown to exert antitumor activity in vivo
      despite its potent antiproliferative activity in vitro. To compare the modes of
      action of UCN-01 and staurosporine in vitro, the effects of both drugs on the
      cell cycle progression of human epidermoid carcinoma A431 cells were examined by
      flow cytometry using propidium iodide (PI) staining. At 50% growth inhibitory
      concentrations, both UCN-01 and staurosporine induced G1 phase accumulation in
      the cell cycle. At 80% growth inhibitory concentrations, UCN-01 also induced
      preferential G1 phase accumulation, but staurosporine mostly induced G2M phase
      accumulation. Staurosporine also induced higher DNA ploidy when the cells were
      exposed to the drug for more than one generation time of A431 cells. An analysis
      of cell kinetics by 5-bromo-2-deoxyuridine incorporation versus DNA content
      confirmed that the G1 phase block by UCN-01 and the G1 and G2M phase block by
      staurosporine at the respective doses, as was the case for PI staining.
      Additionally, DNA synthesis of the cells, which was determined by the uptake of
      3H-TdR, was not suppressed at least 8 h after the treatment with UCN-01. These
      results suggested that UCN-01 could affect the G1 phase of cell cycle in A431
      cells in quite different manners from staurosporine. The G1 phase block induced
      by UCN-01 might be important for the growth inhibitory activity of UCN-01 against
      A431 cells in vitro and in vivo.

PMID- 7506639
TI  - Interaction of acute ventricular dilatation and d-sotalol during sustained
      reentrant ventricular tachycardia around a fixed obstacle.
AB  - BACKGROUND: Antiarrhythmic therapy of ventricular tachycardia is associated with
      decreased efficacy and increased proarrhythmia in patients with congestive heart
      failure, but the explanation for these observations is not known. This study
      examined the interaction of ventricular dilatation and d-sotalol in a model of
      reentry ventricular tachycardia. METHODS AND RESULTS: Thin epicardial layers of
      anisotropic myocardium were created in Langendorff-perfused rabbit left
      ventricles by a cryo procedure. A fluid-filled, latex balloon was secured within
      the left ventricle to change ventricular volume. Sustained reentrant ventricular
      tachycardia, around a central cryolesion, was induced by rapid pacing in all
      preparations (n = 7). Epicardial mapping was performed through 248 electrodes.
      Single premature beats introduced within the reentry circuit were used to define
      the excitable gap. Dilatation did not influence ventricular tachycardia cycle
      length or conduction velocity. A 1.25-mL increase in left ventricular volume
      widened the excitable gap by 12% (range, 5% to 29%) (P < .001) because of a
      decrease in myocardial refractoriness. d-Sotalol (final concentration, 10 mg/L)
      narrowed the excitable gap 18% (range, 7% to 29%) (P = .002) in the undilated
      left ventricle. d-Sotalol was less effective in the dilated left ventricle,
      narrowing the excitable gap only 9%, a difference that was not statistically
      significant. During pacing to induce or terminate tachycardia, tachycardia
      acceleration was observed significantly more frequently in the dilated than in
      the undilated ventricle. Ventricular tachycardia acceleration was due to the
      development of double-wave reentry (two successive waves traveling in the same
      circuit in the same direction). d-Sotalol, which narrowed the excitable gap,
      prevented tachycardia acceleration and double-wave reentry. CONCLUSIONS:
      Antiarrhythmic efficacy may be decreased by dilatation because of widening of the
      initial excitable gap and a decrease in the gap-narrowing effect of these agents.
      Double-wave reentry, more likely with a widening of excitable gap, may partially
      explain tachycardia acceleration in the dilated ventricle.

PMID- 7506640
TI  - Significance of glomerular deposition of plasmin-alpha 2-plasmin inhibitor
      complexes in various glomerulopathies.
AB  - To elucidate the relationship between glomerular deposition of plasmin-alpha 2
      plasmin inhibitor complexes (PIC) and renal lesions or dysfunction, 25 patients
      with various glomerulopathies and various degrees of renal injuries were
      examined. Glomerular PIC deposition was found in eight patients (group A), and
      other 17 patients showed no deposition (group B). PIC was found mainly in the
      mesangium and along the capillary loops. Group A showed significantly more severe
      hematuria (p < 0.05) than group B. Group A showed a significant decrease in
      glomerular filtration rate (GFR; p < 0.05): the mean values being 60.8 +/- 39 in
      group A and 94.5 +/- 32 ml/min in group B. Group A showed a significant decrease
      in the phenolsulfonphthalein excretion test (p < 0.05). There was no significant
      difference in the mean values of plasma PIC, D-dimer, and thrombin-antithrombin
      III complexes (TAT) between two groups. Histologically, group A showed a
      significantly high incidence of adhesion (p < 0.05), crescentic formation (p <
      0.05), endothelial swelling and/or detachment (p < 0.01), tubulointerstitial
      changes (p < 0.01), and glomerular deposition of platelet factor 4 (p < 0.01).
      The present study demonstrates that glomerular PIC deposition reflects the
      existence of activation of coagulation and fibrinolysis within the glomeruli and
      suggests that glomerular PIC deposition plays a part in the progression of renal
      injuries in various glomerulopathies.

PMID- 7506641
TI  - Decreased incidence of viral infections in liver transplant recipients. Possible
      effects of FK506?
AB  - Cytomegalovirus (CMV) is a major infectious complication of organ transplantation
      and its incidence is influenced by the type and intensity of immunosuppressive
      therapy employed. Using a new immunosuppressive agent FK506, CMV infection was
      observed in 30% and CMV disease in 15% of the 26 liver transplant recipients.
      Delayed onset of CMV disease was noted; the mean time to the occurrence of CMV
      disease being 137 days posttransplantation. No graft loss or mortality could be
      attributed to CMV infection. Mucocutaneous herpes simplex virus (HSV) infections
      were encountered in 19% of the patients, while no disease could be attributed to
      varicella zoster virus or Epstein-Barr virus (EBV). The contribution of FK506 to
      a decrease in viral morbidity and associated mortality bears further
      investigation.

PMID- 7506642
TI  - Clinical course of acute hepatitis C and changes in HCV markers.
AB  - Chronological measurements of various HCV markers were conducted to clarify the
      course and prognosis of acute hepatitis C. Among 49 patients with acute non-A,
      non-B hepatitis, 32 (65.3%) were diagnosed as having acute hepatitis C by these
      markers. Twenty-four (82.8%) of 29 patients with posttransfusion hepatitis were
      type C, while only eight (40.0%) of 20 patients with sporadic hepatitis were type
      C. Patients were also divided into those who returned to normal within one year
      based on changes in s-ALT levels and unresolved cases. Anti-HCV was present in 11
      (44.4%) of 25 resolved cases and in 21 (87.1%) of 24 unresolved cases. Only one
      case was continuously positive for HCV-RNA although s-ALT levels returned to
      normal. In addition, quantitative determinations were conducted on those positive
      for anti-HCVs. Anti-second generation tested positive in all HCV-RNA-positive
      cases and positive rates were highest from the onset of hepatitis. In unresolved
      patients with continuous HCV infection, anti-core increased and titers at 12
      months were 10 units or more in all cases. On the other hand, in eight of 10
      resolved cases, titers declined gradually after initial seroconversion and titers
      were 10 units or less at 12 months. From these results, second generation anti
      HCV was considered most useful in early diagnosis of acute hepatitis C and anti
      core titer was considered most useful in predicting prognosis of acute hepatitis
      C.

PMID- 7506643
TI  - Listeria monocytogenes peritonitis in cirrhotic patients. Value of ascitic fluid
      gram stain and a review of literature.
AB  - Listeria monocytogenes has been increasingly implicated in spontaneous bacterial
      peritonitis in patients with cirrhosis. This bacterium can be mistaken for
      diphtheroids and gram-positive cocci if special attention is not paid to the
      motility pattern and specific biochemical tests. Although the sensitivity of
      ascitic fluid Gram stain is low, we describe a case in which the Gram stain of
      the ascites fluid was positive. This issue is now pertinent given recent
      recommendations of third-generation cephalosporin antibiotics as empiric therapy
      for spontaneous bacterial peritonitis; Listeria is resistant to cephalosporin
      agents. A positive Gram stain could affect the empiric antibiotic therapy. We
      review the clinical presentation and outcome in nine other cases of Listeria
      peritonitis occurring in cirrhotic patients.

PMID- 7506644
TI  - Prospective assessment of incidence of fulminant hepatitis in post-transfusion
      hepatitis: a study of 504 cases.
AB  - The incidence of posttransfusion hepatitis and "fulminant" hepatitis was
      investigated by a plan devised at our hospital in December 1982. Of 2959 blood
      recipients between January 1982 and December 1988, 504 (22.5%) developed
      posttransfusion hepatitis, with a mean transfusion volume of 10.2 units. Of the
      504 cases of posttransfusion hepatitis, "icteric" (T-Bil > 2.0 mg/dl) and "overt
      icteric" hepatitis (T-Bil > 5.0 mg-dl) developed in 111 cases (22.0%) and 28
      cases (5.6%), respectively. Of the 28 overt icteric hepatitis cases, 13 (2.8%)
      were thought to be true overt icteric posttransfusion hepatitis because the
      icterus was caused by other reasons in the other 15 cases (seven neonatal
      jaundice, four hemolytic anemia, one radiation hepatitis, one halothane-induced
      hepatitis; two other cases were excluded because chronic liver disease was
      diagnosed by imaging procedures despite serum ALTs in the normal range before
      transfusion). The anti-HCV serostatus was investigated in five of the 13 true
      overt icteric posttransfusion hepatitis patients using blood specimens taken 180
      days or more following the onset of posttransfusion hepatitis. Anti-HCV
      seroconversion occurred in three of the five cases (60%). HCV seroconversions
      were not seen in the cases in which the icterus was due to other reasons.

PMID- 7506645
TI  - [alpha 2-macroglobulin in urine. Significance for differential diagnosis of
      rejection and infections after kidney transplantation].
AB  - The value of measuring the urinary concentration of alpha 2-macroglobulin in
      addition to that of C-reactive protein (CRP) was assessed in a prospective study
      of 78 consecutive patients (29 women, 49 men; mean age 48.7 [19-75] years) after
      renal transplantation. alpha 2-Macroglobulin was never demonstrated in urine when
      the course was normal (n = 38), cytomegalovirus infection had occurred (n = 26)
      or acute cyclosporin nephrotoxicity (n = 5) or glomerular disease in the
      transplant (n = 10). CRP was present in only a few such cases. Interstitial
      rejections (n = 26) always led to urinary alpha 2-macroglobulin and CRP excretion
      without haematuria, while in vascular rejection (n = 3) the haemoglobin test was
      also positive. Urinary infection (n = 20) and urosepticaemia (n = 6) always
      brought about the urinary excretion of alpha 2-macroglobulin and CRP, as well as
      a usually highly positive haemoglobin test. alpha 2-Macroglobulin was absent but
      CRP always present in extrarenal bacterial infections (n = 30). Postrenal blood
      admixture was always characterized by a positive haemoglobin test and alpha 2
      macroglobulin in urine, while in most cases (83%) CRP was absent. --These results
      indicate that the constellation "alpha 2-macroglobulin negative/CRP positive" is
      a pathognomonic for extrarenal bacterial infection (sensitivity 100%, specificity
      98.9%). The presence of alpha 2-macroglobulin alone makes postrenal blood
      admixture probable. If both proteins are present in the urine, rejection and
      urogenital bacterial infection must be excluded by further tests.

PMID- 7506646
TI  - Ethical issues and clinical trials.

PMID- 7506647
TI  - Newer antipsychotic drugs. A review of their pharmacology and therapeutic
      potential.
AB  - Despite the enormous benefits provided by antipsychotic medication in the
      management of schizophrenia, available compounds have serious limitations.
      Firstly, they are not always effective. Secondly, positive psychopathological
      symptoms may benefit more than negative or deficit symptoms. Thirdly,
      antipsychotics are generally associated with a variety of neurological adverse
      effects. Three drugs have recently been or are close to being introduced into
      widespread clinical use: clozapine, risperidone and remoxipride. Each of these
      compounds appears to have some advantages over traditional antipsychotic agents,
      particularly in terms of reduced propensity to induce adverse neurological
      effects. All three drugs have been shown to be clinically effective in large
      scale trials. Future clinical trials are required to establish their relative
      merits in comparison with one another.

PMID- 7506650
TI  - Treatment of the chronic fatigue syndrome. A review and practical guide.
AB  - The chronic fatigue syndrome (CFS) was formally defined in 1988 to describe a
      syndrome of severe and disabling fatigue of uncertain aetiology associated with a
      variable number of somatic and/or psychological symptoms. CFS has been reported
      in most industrialised countries and is most prevalent in women aged between 20
      and 50 years. Despite occasional claims to the contrary, the aetiology of CFS
      remains elusive. Although abnormalities in tests of immune function and cerebral
      imaging have been described in variable numbers of CFS patients, such findings
      have been inconsistent and cannot be relied upon, either to establish or exclude
      the diagnosis. Thus, diagnosis rests on fulfillment of the Centers for Disease
      Control case definition which was revised in 1992. This case definition remains
      somewhat controversial, largely due to its subjectiveness. The mainstay of
      treatment is establishing the diagnosis and educating the patient about the
      illness. An empathetic clinician can stop further consultations elsewhere
      ('doctor shopping') and subsequent excessive investigations, which frequently
      occur in such patients. Most patients should undertake a trial of antidepressant
      therapy, even if major depression is not present. The choice of antidepressant
      drug should tailor the tolerability profile to relief of particular CFS symptoms,
      such as insomnia or hypersomnia. Failure to improve within 12 weeks warrants an
      alternative antidepressant agent of another class. Many other drugs have been
      reported anecdotally to be beneficial, but no therapy has been demonstrated to be
      reproducibly useful in double-blind, placebo-controlled clinical trials with an
      adequate duration of follow-up.

PMID- 7506651
TI  - Pentostatin. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic potential in lymphoproliferative disorders.
AB  - Pentostatin, a potent inhibitor of adenosine deaminase, is an antineoplastic
      agent which has been studied in the treatment of a variety of lymphoproliferative
      disorders. It is particularly effective in the treatment of hairy cell leukaemia,
      achieving complete remissions in 33 to 92% of patients, and has useful activity
      in treating B cell chronic lymphocytic leukaemia, prolymphocytic leukaemia, adult
      T cell leukaemia/lymphoma and cutaneous T cell lymphoma refractory to
      conventional chemotherapy. Initial results suggest that in the treatment of hairy
      cell leukaemia pentostatin achieves a more rapid response and higher frequency of
      complete remission with longer duration than interferon-alpha 2a, although it is
      still not known if some patients experiencing complete remission have been cured.
      The drug has yet to be directly compared with other promising purine analogues
      such as cladribine and fludarabine, and results of such comparisons are required
      before the ultimate role of pentostatin in the treatment of hairy cell leukaemia
      can be clearly established. However, pentostatin does produce a substantial
      response in a difficult therapeutic area and should be considered for initial
      treatment of hairy cell leukaemia.

PMID- 7506649
TI  - Liposomes as carriers of cancer chemotherapy. Current status and future
      prospects.
AB  - Chemotherapy is a modality of cancer therapy that needs much improvement.
      Development of a new chemical entity is very costly and time consuming, but
      improvements in delivery of existing agents may yield more rapid clinical
      results. Liposomes and other lipid-based drug delivery systems have the
      advantage, in this context, of utilising no new chemical entities. In terms of
      mechanism of action, tumour targeting has been the focus of much work in
      liposomal drug delivery. The recent development of liposomes with longer
      circulation times has led to improved tumour targeting in animal studies. Other
      mechanisms of action, such as release from drug depot formulations, heat
      triggered local drug release, and transfection of genetic materials, may prove to
      be useful in humans. Liposomal formulations of more than a dozen antineoplastic
      agents have shown promise in vitro and in animal models. Somewhat mundane, but
      nevertheless crucial, issues of medical rationale and formulation engineering,
      and commercial considerations, have slowed testing in patients with cancer.
      However, 3 antineoplastic agents, doxorubicin, daunorubicin and cytarabine, are
      in advanced stages of clinical testing in humans. One or more of these should
      prove to be a medically useful and commercially viable product within the next
      few years.

PMID- 7506648
TI  - Drugs used in the treatment of metabolic bone disease. Clinical pharmacology and
      therapeutic use.
AB  - Osteoporosis is the most important metabolic bone disease and places an
      increasing burden on the healthcare system. The condition can be prevented by the
      early introduction of hormone replacement therapy. The role of bisphosphonates in
      achieving the same result is being actively explored. The attraction of
      preventing bone loss is that it preserves the micro-architecture of bone, and
      therefore its mechanical integrity. The great problem of treating the established
      condition is that substantial bone loss is accompanied by architectural
      disintegration. Replacing lost bone may not necessarily restore mechanical
      integrity and protect against fractures. The management of Paget's disease has
      been quite revolutionised by the introduction of the bisphosphonates. The
      condition is a result of a primary increase in osteoclastic bone resorption which
      can be corrected by bisphosphonates, with considerable symptomatic improvement.
      The increasing potency and safety margin of the newer agents has meant that the
      threshold for treatment has fallen. There is now potential for long term control
      of bone turnover with the hope of preventing late complications. Hypercalcaemia
      of malignancy is usually the result of both increased bone destruction and
      decreased urinary calcium excretion. These two components of hypercalcaemia
      demand different approaches to management. The general availability of an ever
      expanding range of increasingly potent bisphosphonates has resulted in a dramatic
      improvement in the treatment of increased bone resorption associated with
      malignancy. Many types of tumour, either directly or indirectly, compromise the
      ability of the kidney to eliminate a calcium load derived from increased bone
      destruction. Calcitonin is the only agent which is currently available to counter
      this process.

PMID- 7506653
TI  - Miocamycin. A review of its antimicrobial activity, pharmacokinetic properties
      and therapeutic potential.
AB  - Miocamycin is an orally administered 16-membered macrolide antimicrobial drug. It
      has a spectrum of in vitro activity similar to that of erythromycin, inhibiting a
      range of Gram-positive and Gram-negative organisms, atypical microbes and some
      anaerobes. Importantly, miocamycin demonstrates greater in vitro potency than
      erythromycin against several pathogens including Legionella pneumophila,
      Mycoplasma hominis, and Ureaplasma urealyticum. Equally noteworthy is its
      activity against erythromycin-resistant staphylococcal and streptococcal species
      expressing inducible-type resistance. Miocamycin possesses poor overall activity
      against Haemophilus influenzae and is inactive against Enterobacteriaceae.
      Penetration of miocamycin into body tissues and fluids is both rapid and
      extensive. The 3 major metabolites of miocamycin possess antimicrobial activity
      and may contribute to the therapeutic efficacy of the drug. Clinical data
      indicate that miocamycin is useful in the treatment of upper and lower
      respiratory tract infections in both adult and paediatric patients. Miocamycin is
      also effective in the treatment of urogenital tract infections caused by
      Chlamydia trachomatis or U. urealyticum. Several studies suggest that miocamycin
      is at least as effective as erythromycin in these indications; however,
      comparisons with newer macrolide agents have yet to be performed. In other
      studies, miocamycin proved to be a useful agent in the treatment of periodontal
      infections and as anti-infective prophylaxis in dental surgery. Miocamycin
      appears to have a tolerability profile qualitatively similar to that of other
      macrolides, with gastrointestinal and skin disorders being the most commonly
      reported adverse events. Current data suggest that the potential for drug
      interactions with miocamycin is low, with the possible exceptions of
      carbamazepine and cyclosporin. Thus, although further confirmation and
      elaboration of various aspects of its efficacy and tolerability profile is
      needed, at this stage miocamycin offers a useful alternative oral therapy to
      erythromycin for the treatment of uncomplicated community-acquired respiratory
      tract infections and nongonococcal urethritis.

PMID- 7506657
TI  - Equine infectious anemia virus Tat is a predominantly helical protein.
AB  - Nuclear magnetic resonance (NMR) spectroscopy revealed features of the secondary
      structure of the equine infectious anemia virus (EIAV) Tat protein in solution.
      We could show that this protein, which is required in the replication cycle of
      lentiviruses, forms a predominantly helical structure in trifluoroethanol/water
      (40% by vol.) solution. In particular, the basic RNA-binding region and the
      adjacent core domain, which are highly conserved among lentiviral Tat proteins,
      show helix-type secondary structure under these conditions. Our observations, in
      concert with recent biochemical data from other laboratories, suggest that the
      core sequence region and the basic sequence region form interdependent structural
      domains, both possibly necessary for correct RNA binding.

PMID- 7506655
TI  - Plasminogen-activator inhibitor type 2 (PAI-2) is a spontaneously polymerising
      SERPIN. Biochemical characterisation of the recombinant intracellular and
      extracellular forms.
AB  - Plasminogen-activator inhibitor type 2 (PAI-2) is a specific inhibitor of
      plasminogen activators (PA) that exists in an intracellular, low-molecular-mass
      form and a secreted, high-molecular-mass form that varies with respect to
      glycosylation. Here we have developed expression systems for both forms of PAI-2
      and biochemically characterised the purified proteins. In order to obtain
      efficient secretion, we constructed an artificial signal sequence and fused it to
      the coding region of PAI-2. With this construct, more than 90% of PAI-2 was
      secreted as a glycosylated, 60-kDa molecular-mass form, but the level of
      expression was low and unstable. To obtain higher expression of secreted PAI-2, a
      novel expression vector based on the Semliki-forest-virus replicon was used.
      Secreted PAI-2 was purified to homogeneity and N-terminal sequence analysis
      showed that the artificial signal peptide was correctly removed. The
      intracellular, non-glycosylated form of PAI-2 was expressed in Escherichia coli
      and purified to homogeneity. Both the secreted and the intracellular forms of PAI
      2 were found to inhibit plasminogen activators by forming SDS-resistant complexes
      and the second-order rate constants were similar for both forms, ranging over 2.4
      2.7 x 10(6) M-1s-1 for urokinase-type PA, 2.5-2.7 x 10(5) M-1s-1 for two-chain
      tissue-type PA and 0.8-1.2 x 10(4) M-1s-1 for single-chain tissue-type PA. None
      of the purified PAI-2 forms bound to vitronectin. Circular-dichroism spectral
      analysis revealed that PAI-2 has a CD spectrum that resembles ovalbumin more than
      PA-inhibitor type 1, confirming the greater similarity between these two members
      of the serine-protease inhibitor family. Similar to what has been described for
      the Z-form of alpha 1-antitrypsin, purified PAI-2 was found to spontaneously form
      polymers during incubation at room temperature. Attempts to convert PAI-2 to a
      stable locked conformation resembling the conformation of latent PAI-1 by
      treatment with diluted guanidinium chloride were unsuccessful. Instead, this
      treatment enhanced the formation of PAI-2 polymers, possibly by the loop-sheet
      polymerisation mechanism described for alpha 1-antitrypsin.

PMID- 7506656
TI  - Structures of the N-linked oligosaccharides on porcine plasma vitronectin.
AB  - The structures of N-linked oligosaccharides, especially the distribution of
      sialic acid species, present on porcine plasma vitronectin were elucidated.
      Oligosaccharides were released from the vitronectin by N-glycosidase F digestion
      and tagged with 2-aminopyridine, and the pyridylamino-oligosaccharides were
      fractionated by anion-exchange and reverse-phase HPLC. Nine major pyridyl-amino
      oligosaccharides were isolated. The linkages and locations of sialic acids were
      determined by a novel approach involving desialylation with Salmonella sialidase
      in combination with acid desialylation. After desialylation, the asialo-forms
      were analyzed by two-dimensional sugar mapping, component sugar analysis and 400
      MHz 1H-NMR spectroscopy. The major oligosaccharides of porcine vitronectin were
      of the fucosylated biantennary type, with a small amount of the triantennary N
      acetyllactosamine type, to which 1-3 mol sialic acids was linked. Sialic acids
      were linked predominantly through alpha 2-6 linkages, although alpha 2-3 linkages
      were also present, and fucose was linked to the innermost N-acetylglucosamine
      through an alpha 1-6 linkage. It was found that every pyridylamino
      oligosaccharide population contained N-glycolylneuraminic acid and N
      acetylneuraminic acid in a molar ratio of 1:2-9, and that N-glycolylneuraminic
      acids were located predominantly on the Man alpha 1-6 arm.

PMID- 7506658
TI  - Effect of glutamate receptor antagonists on N-methyl-D-aspartate- and (S)-alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced convulsant effects in
      mice and rats.
AB  - Selected antagonists of N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, acting through
      different recognition sites were studied in three in vivo experimental
      procedures: systemic administration of NMDA or AMPA to mice and 7-day-old rats or
      i.c.v. injection in adult rats. Antagonists were given i.p. before the agonists.
      Of the substances tested (+)-5-methyl-10,11- dihydro-5H-dibenzocyclohepten-5,10
      imine maleate ((+)-MK-801, an uncompetitive NMDA receptor antagonist) and DL-(E)
      2-amino-4-methyl-5- phosphono-3-pentanoic acid (CGP-37849, a competitive NMDA
      receptor antagonist) were the most potent and selective NMDA receptor
      antagonists, having ED50s below 1 mg/kg in all three tests. 1-Amino-3,5
      dimethyladamantane (memantine, an uncompetitive NMDA receptor antagonist) was
      less potent and, additionally, inhibited AMPA-induced seizures in adult rats.
      Aminocyclopropane carboxylic acid--a partial agonist at the glycine site coupled
      to NMDA receptors (GlyB)--was a weak antagonist (ED50 > 150 mg/kg) in mice. Other
      partial GlyB receptor agonists, aminocyclobutane carboxylic acid, (+,R)-3-amino-1
      hydroxy-2-pyrrolidine ((+,R)-HA-966) and d-cycloserine, and antagonists, 5,7
      dinitroquinoxaline-2,3-dione (MNQX) and 5,7-dichlorokynurenic acid, were
      ineffective in mice after systemic administration. The last two agents however
      were active in adult rats when given i.c.v. Thus affinity, intrinsic activity
      (GlyB receptor partial agonists) and/or penetration into the brain (GlyB receptor
      antagonists) seem to be important factors in determining the effectiveness of
      these agents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506659
TI  - A new selective bioassay for tachykinin NK3 receptors based on inositol
      monophosphate accumulation in the guinea pig ileum.
AB  - The selective agonists of tachykinin NK1, NK2 and NK3 receptors, respectively
      [Pro9]substance P, [Lys5,MeLeu9,Nle10]neurokinin A-(4-10) and senktide,
      stimulated phosphoinositide breakdown in slices of the guinea pig ileum. This was
      also the case with septide which has recently been found to act on a new type of
      tachykinin receptors in this tissue. The NK1, NK2 and septide-evoked responses
      were completely antagonized in the combined presence of (+/-)-CP-96,345 and MEN
      10,376 which are potent and selective antagonists of tachykinin NK1 and NK2
      receptors respectively in the guinea pig ileum. Like senktide, other available
      NK3 receptor agonists, such as [MePhe7]neurokinin B, [MeVal7]neurokinin B,
      [Pro7]neurokinin B and DiMe-C7, stimulated phosphoinositide hydrolysis in either
      the absence or combined presence of (+/-)-CP-96,345 and MEN 10,376, although
      senktide was the most potent. Therefore, following the blockade of tachykinin
      NK1, NK2 and septide-sensitive receptors, the accumulation of inositol
      monophosphate appears to be a valuable, rapid and sensitive bioassay for
      determining the activity of NK3 receptor agonists and putative NK3 receptor
      antagonists.

PMID- 7506661
TI  - Uncoupling of beta 1-adrenoceptors from cardiac adenylyl cyclase in
      cardiomyopathic and control hamsters.
AB  - The beta-adrenoceptor-adenylyl cyclase system was studied in heart ventricles
      from Wistar rats, cardiomyopathic (BIO 8262) and nonfailing control hamsters
      (CLAC) using the beta 1-adrenoceptor antagonist CGP 20712A. In radioligand
      binding studies, the majority of beta-adrenoceptors in ventricles from rats as
      well as from CLAC hamsters was of the beta 1-subtype (72.2% and 76.6%,
      respectively). In BIO ventricles a significant (CLAC vs. BIO, P < 0.05) reduction
      in the beta 1-subtype (62.9%) was found. In Wistar rats the subtype-mediated
      stimulation of adenylyl cyclase reflected the beta 1:beta 2 ratio as determined
      by binding studies. In hamster ventricles the effect of isoprenaline was mediated
      predominantly (CLAC) or exclusively (BIO) via the beta 2-subtype, indicating that
      cardiac beta 1-adrenoceptors were partly (CLAC) or completely (BIO) uncoupled
      from the adenylyl cyclase.

PMID- 7506660
TI  - The nicotinic acetylcholine receptor of the bovine chromaffin cell, a new target
      for dihydropyridines.
AB  - The effects of 1,4-dihydropyridine derivatives on divalent cation transients and
      catecholamine release stimulated by either high K+ or the nicotinic receptor
      agonist dimethyl-phenyl-piperazinium (DMPP) have been compared in bovine adrenal
      chromaffin cells. The activation of Ca2+ entry pathways was followed by measuring
      45Ca2+ or Mn2+ uptake, or by the changes of [Ca2+]i in fura-2-loaded chromaffin
      cells. Various dihydropyridine Ca2+ channel blockers (nimodipine, PCA50938,
      nifedipine, nitrendipine, furnidipine) abolished the DMPP-mediated effects, but
      prevented only partially the activation by high [K+]0 of 45Ca2+ uptake. The IC50
      for DMPP-induced activation was around 1 microM. The L-type Ca2+ channel
      activator Bay K 8644 potentiated the uptake of 45Ca2+ induced by K+
      depolarization at concentrations between 10 nM and 1 microM, but completely
      inhibited the uptake of 45Ca2+ by DMPP (IC50, 0.9 microM). Both high [K+]0 and
      DMPP produced membrane depolarization as measured using bis-oxonol. The DMPP
      evoked, but not the K(+)-evoked membrane depolarization was prevented by Na+
      removal, suggesting that the depolarization was due to Na+ entry through the
      acetylcholine receptor ionophore. Nimodipine at 10 microM abolished the
      depolarization induced by DMPP, leaving the K(+)-evoked depolarization
      unaffected. Tetrodotoxin (2 microM) did not affect the DMPP- or high K(+)
      mediated cell depolarization. Whole-cell inward current evoked by 100 microM DMPP
      (IDMPP) was measured in cells voltage-clamped at -80 mV. Nimodipine (10 microM)
      reduced IDMPP by 36%; Bay K 8644 (10 microM) inhibited IDMPP by 67%. DMPP-evoked
      catecholamine release from superfused chromaffin cells was reduced by over 90%
      with 10 microM nimodipine; in contrast, K(+)-evoked release was decreased by
      20%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506652
TI  - Sotalol. An updated review of its pharmacological properties and therapeutic use
      in cardiac arrhythmias.
AB  - Sotalol is a nonselective beta-adrenoceptor antagonist which prolongs cardiac
      repolarisation independently of its antiadrenergic action (class III
      antiarrhythmic properties). The antiarrhythmic action of sotalol appears to arise
      predominantly from its class III properties, and the drug exhibits a broader
      antiarrhythmic profile than the conventional beta-blockers. Sotalol is effective
      in controlling paroxysmal supraventricular tachycardias and the ventricular
      response to atrial fibrillation/flutter in Wolff-Parkinson-White syndrome, in
      maintaining sinus rhythm after cardioversion of atrial fibrillation/flutter, and
      in preventing initiation of supraventricular tachyarrhythmias following coronary
      artery bypass surgery. Sotalol shows promise in the control of nonmalignant and
      life-threatening ventricular arrhythmias, particularly those associated with
      ischaemic heart disease. It is effective in suppressing complex forms of
      ventricular ectopy, displaying superior antiectopic activity to propranolol and
      metoprolol. The acute efficacy of sotalol in preventing reinduction of sustained
      ventricular tachyarrhythmias and suppressing spontaneous episodes of these
      arrhythmias on Holter monitoring is translated into long term prophylactic
      efficacy against arrhythmia recurrence in approximately 55 to 85% of patients
      with refractory life-threatening ventricular arrhythmias. In addition, sotalol
      offers the advantage over the class I agents of reducing cardiac and all-cause
      mortality in the high risk population with life-threatening ventricular
      arrhythmias. The adverse effects of sotalol are primarily related to its beta
      blocking activity and its class III property of prolonging cardiac
      repolarisation. Sotalol is devoid of overt cardiodepressant activity in patients
      with mild or moderate left ventricular dysfunction. The overall arrhythmogenic
      potential is moderately low, but torsade de pointes may develop in conjunction
      with excessive prolongation of the QT interval due to bradycardia, hypokalaemia
      or high plasma concentrations of the drug. In summary, sotalol displays a broad
      spectrum of antiarrhythmic activity, is haemodynamically well tolerated, and
      confers a relatively low proarrhythmic risk. It is likely to prove particularly
      appropriate in the treatment and prophylaxis of life-threatening ventricular
      tachyarrhythmias.

PMID- 7506662
TI  - Increased platelet activating factor synthesis in experimental colitis after
      diclofenac and 5-amino-salicylic acid.
AB  - We examined the role of platelet activating factor in dextran induced colitis in
      mice. The release of pro-inflammatory platelet activating factor by colonic
      mucosa after the application of prednisolone was markedly decreased, unaffected
      after treatment with the platelet activating factor receptor antagonist BN52021
      and significantly increased after treatment with 5-amino-salicylic acid and
      diclofenac. This increase of platelet activating factor could be responsible for
      the harmful effects often seen after treatment with specific cyclooxygenase
      inhibitors during inflammation.

PMID- 7506663
TI  - Anti-emetic profile of a non-peptide neurokinin NK1 receptor antagonist, CP
      99,994, in ferrets.
AB  - In the ferret, 5-HT3 receptor antagonists are effective in controlling emesis
      produced by cytotoxic agents or radiation. To investigate the possibility that
      substance P has a role, as well as 5-HT, in the emetic reflex pathway, we have
      examined the anti-emetic effects of a NK1 receptor antagonist (racemic CP-99,994)
      in the ferret. Racemic CP-99,994 was effective against a range of emetogens,
      comprising cytotoxic drugs, radiation, morphine, ipecacuanha and copper sulphate.

PMID- 7506664
TI  - Inhibition of nitric oxide formation by guanidines.
AB  - Aminoguanidine, N,N'-diaminoguanidine, methylguanidine, and 1,1-dimethylguanidine
      were compared to NG-monomethyl-L-arginine (L-NMMA) for their ability to inhibit
      nitric oxide (NO) formation by cytokine-inducible and vascular constitutive
      isoforms of NO synthase. These comparisons were performed by assessing (1)
      cytokine-induced production of nitrite by RINm5F cells, (2) vasoconstrictor
      responses of isolated rat mesenteric arteries, and (3) in vivo blood pressure
      responses following intravenous bolus injection into anesthetized rats.
      Aminoguanidine and L-NMMA were the most potent inhibitors of cytokine-induced NO
      formation in RINm5F cells, while the other guanidine compounds were 10 (1,1
      dimethylguanidine) to 100 (methylguanidine) times less potent. L-NMMA and 1,1
      dimethylguanidine were the most potent inhibitors of the vascular constitutive
      isoform of NO synthase in both assay systems, while aminoguanidine and N,N'
      diaminoguanidine were the least potent. These results (1) confirm the selective
      inhibition of the inducible isoform of NO synthase by aminoguanidine, (2)
      indicate that N,N'-diaminoguanidine, while approximately 30 times less potent
      than aminoguanidine in inhibiting inducible NO synthase, has very little effect
      on constitutive NO synthase activity, and (3) 1,1-dimethylguanidine, like L-NMMA,
      is a relatively potent inhibitor of both isoforms of NO synthase.

PMID- 7506665
TI  - Three novel synthetic retinoids, Re 80, Am 580 and Am 80, all exhibit anti
      angiogenic activity in vivo.
AB  - In a previous study, we demonstrated that retinoic acid or a synthetic retinoid,
      Ch 55 ((E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid),
      significantly affects in vivo angiogenesis, on the basis of our working
      hypothesis that a cell differentiation modulator could also exhibit anti
      angiogenic activity. In the present study, three novel synthetic retinoids, Re 80
      (4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl- 2-
      naphthalenyl)-1-propenyl]benzoic acid), Am 580 (4-[(5,6,7,8-tetrahydro- 5,5,8,8
      tetramethyl-2-naphthalenyl)carboxamido]benzoic acid) and Am 80 (4-[(5,6,7,8
      tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl] benzoic acid), whose
      cell differentiation-modulating effects are roughly comparable to or more potent
      than that of Ch 55, which was the most effective angiostatic retinoid identified
      previously, were examined. Their anti-angiogenic effects were tested in an in
      vivo assay system involving chorioallantoic membranes of growing chick embryos.
      They were all found to exert dose-dependent anti-angiogenic effects in the
      picomolar range. Their rank order for inhibitory potency was Re 80 > Am 580 > Am
      80, the ID50 values being 6.3, 23 and 28 pmol/egg, respectively. These results
      indicate that treatment involving these three novel synthetic retinoids might
      have potential therapeutic efficacy in various angiogenesis-dependent disorders,
      including solid tumors, psoriasis, rheumatoid arthritis and diabetic retinopathy.

PMID- 7506666
TI  - Quantification of presynaptic alpha 2-adrenoceptors in rat brain after short-term
      DSP-4 lesioning.
AB  - The relative numbers of pre- and postsynaptic alpha 2-adrenoceptors were
      determined in various rat brain regions after short-term DSP-4 (N-(2-chloroethyl)
      N-ethyl-2-bromobenzylamine) lesioning. For these studies, rats pretreated with
      zimeldine (10 mg/kg i.p.) were injected with DSP-4 (100 mg/kg i.p.) and were
      killed either 3 or 15 days later. At the 3 day time-point, DSP-4 treatment
      produced marked reductions in the noradrenaline content of the cortex (93%),
      hippocampus (89%), hypothalamus (83%) and cerebellum (92%) with no change in the
      levels of dopamine or 5-HT. This treatment also decreased the number of alpha 2
      adrenoceptors labelled with [3H]idazoxan in the cortex (20%), hippocampus (18%),
      cerebellum (24%) and hypothalamus (39%). Fifteen days after DSP-4 lesioning, the
      marked reductions of noradrenaline were sustained in the cortex, hippocampus and
      cerebellum, but there was a considerable reversal of the effect of DSP-4 in the
      hypothalamus. At this time-point, the decrease in alpha 2-adrenoceptors was
      attenuated in cortex (4%) and cerebellum (0%) and their number was increased in
      hippocampus (8%) and hypothalamus (7%). Together, the data argue that presynaptic
      alpha 2-adrenoceptors comprise approximately 20% of the total alpha 2
      adrenoceptor population in the cortex, hippocampus and cerebellum, but about 40%
      of it in the hypothalamus. Furthermore, they also demonstrate that although the
      number of presynaptic alpha 2-adrenoceptors in rat brain can be determined by the
      reduction of radioligand-receptor binding shortly after DSP-4 lesioning, this
      effect is rapidly masked by receptor proliferation in response to noradrenergic
      denervation.

PMID- 7506654
TI  - Tacrolimus. A review of its pharmacology, and therapeutic potential in hepatic
      and renal transplantation.
AB  - Tacrolimus (FK 506) is a macrolide immunosuppressant which possesses similar but
      more potent immunosuppressant properties compared with cyclosporin, inhibiting
      cell-mediated and humoral immune responses. Like cyclosporin, tacrolimus
      demonstrates considerable interindividual variation in its pharmacokinetic
      profile. This has caused difficulty in defining the optimum dosage regimen and
      has highlighted the usefulness of therapeutic drug monitoring. Most clinical
      studies with tacrolimus have neither been published in their entirety nor
      subjected to extensive peer review; there is also a paucity of published
      randomised investigations of tacrolimus versus cyclosporin, particularly in renal
      transplantation. Despite these drawbacks, tacrolimus has shown notable efficacy
      as a rescue or primary immunosuppressant therapy when combined with
      corticosteroids in adult and paediatric recipients following liver or kidney
      transplantation. Indeed, graft salvage rates in patients experiencing rejection
      or drug-related toxicity were > or = 50%, although data in renal transplantation
      are limited. Compared with cyclosporin as a primary immunosuppressant, tacrolimus
      showed comparable or greater patient/graft survival rates in liver allograft
      recipients (where cost savings associated with reduced hospitalisation costs were
      evident in one study), and comparable patient/graft survival in patients
      following kidney transplantation. Worthy of note was the efficacy of tacrolimus
      as a primary immunosuppressant in patients who received en bloc kidney
      allografts. The incidence of rejection was largely reduced following rescue
      therapy with tacrolimus and was generally lower (notably for refractory
      rejection) than that observed for cyclosporin, at least in liver allograft
      recipients. This was reflected in less need for adjunct immunotherapy including
      antilymphocyte preparations for the treatment of rejection episodes. The
      potential for reduction or withdrawal of corticosteroid therapy with tacrolimus
      appears to be a distinct advantage compared with cyclosporin, and this may be
      enhanced by the reduced incidence of infectious complications and of hypertension
      and hypercholesterolaemia reported by some investigators. In other respects,
      however, the tolerability profile of tacrolimus appears to be broadly similar to
      that of cyclosporin. Against this background, preliminary data indicate that
      tacrolimus provides a valuable therapeutic alternative to retransplantation in
      patients experiencing liver or kidney graft rejection or drug-related toxicity.
      Pending confirmation of initial randomised studies and preliminary results from
      large randomised investigations, tacrolimus may well be considered as an
      alternative primary immunosuppressant to cyclosporin in hepatic (particularly)
      and renal transplantation. Furthermore, the steroid-sparing effects of
      tacrolimus, although of benefit to all patient groups, may prove to be of
      particular worth in children and in en bloc kidney recipients. In these patients
      tacrolimus may well emerge as the drug of choice.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7506667
TI  - Evaluation of the mechanisms underlying the kainate-induced impairment of
      [3H]dopamine release in the rat striatum.
AB  - Kainic acid caused a marked decrease of the electrically evoked release of
      [3H]dopamine from rat striatal slices 4 days after its injection (10
      nmol/microliters) into the corpus striatum. This damage was prevented by the non
      N-methyl-D-aspartate (non-NMDA) receptor antagonist 6,7-dinitroquinoxaline-2,3
      dione (DNQX) when co-injected with kainic acid into the striatum. Prior systemic
      administration of the NMDA selective antagonists (cis-4-phosphonomethyl-2
      piperidine carboxylic acid (CGS 19755), dizocilpine (MK-801) and ketamine did not
      alter the kainate effect. Previous destruction of the cortico-striatal pathway
      abolished the kainate-induced decrease of [3H]dopamine release. When injected
      into the striatum, domoic acid or alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) mimicked kainic acid and damaged the dopaminergic
      nigro-striatal afferents. The [3H]dopamine release evoked by electrical
      stimulation of slices of frontal cortex was unaffected following local injections
      of kainic acid. Taken together, the results indicate that AMPA/kainate receptors
      play a key role in the impairment of [3H]dopamine release caused by kainate in
      the striatum. However, the kainic acid effect is probably indirect since it
      appears to require the availability of endogenous glutamate originating from
      cortico-striatal afferents.

PMID- 7506668
TI  - Cyclosporin derivatives inhibit interleukin 1 beta induction of nitric oxide
      synthase in renal mesangial cells.
AB  - Treatment of mesangial cells with recombinant human interleukin 1 beta dose
      dependently increased nitrite formation due to the induction of a macrophage-type
      of nitric oxide (NO) synthase. Addition of cyclosporin A, cyclosporin G or
      cyclosporin H dose dependently inhibited interleukin 1 beta-induced nitrite
      generation. Half-maximal inhibition was observed at concentrations of 0.9 microM,
      2.0 microM and 3.8 microM of cyclosporin A, cyclosporin G and cyclosporin H,
      respectively. Time-course studies indicated that cyclosporin A could be added up
      to 6 h after the interleukin 1 beta stimulus and still caused maximal inhibition
      of nitrite production. Furthermore, interleukin 1 beta increased NO synthase mRNA
      levels in mesangial cells and this effect was potently suppressed by all three
      cyclosporin derivatives. As cyclosporin H has no immunosuppressive activity,
      these data indicate that the inhibitory effect of the cyclosporin derivatives on
      NO synthase expression is not related to the immunosuppressive action of the
      drugs. This suggestion is further substantiated by the observation that the
      potent immunosuppressants rapamycin and FK506 did not alter interleukin 1 beta
      induced NO synthase mRNA levels or nitrite generation in mesangial cells. In
      summary, these data demonstrate that cyclosporin derivatives potently modulate
      the L-arginine-NO pathway in renal mesangial cells.

PMID- 7506669
TI  - Substance P inactivation by aqueous humor.
AB  - Degradation of substance P was studied in dog and rabbit aqueous humor. Substance
      P inactivation was followed by the bioassay using the isolated guinea pig ileum.
      Both rabbit and dog aqueous humor inactivated substance P. Rabbit aqueous humor
      inactivated the peptide faster than dog aqueous humor. Inactivation of substance
      P by rabbit aqueous humor was inhibited by diisopropylfluorophosphate while other
      enzyme inhibitors tested (captopril, phosphoramidon, mersalyl acid and p
      chloromercuriphenyl-sulphonate) were practically ineffective or had a partial
      inhibitory effect. Our results suggest that serine proteases, rather than other
      peptidases, play a major role in the inactivation of substance P in aqueous
      humor.

PMID- 7506670
TI  - Tissue culture of rabbit ciliary body epithelial cells on permeable supports.
AB  - The aqueous humor is produced by the epithelium of the ciliary body, a complex
      structure encircling the anterior segment of the eye. Aqueous humor production
      occurs by active transport, but the mechanism of this process is not understood.
      To produce a preparation in which active transport can be investigated, we have
      attempted to prepare cultures suitable for measurements of ion and water flux. We
      have grown rabbit ciliary body epithelial cells on permeable supports, coated
      with several extracellular matrix proteins. We then examined the ability of these
      proteins to promote the growth of a differentiated layer of epithelial cells. Non
      pigmented and pigmented cells formed sheets of contiguous cells when grown on a
      variety of support media. The most successful substrate was a permeable support
      produced by Falcon/Becton Dickinson coated with a mixture of collagen IV, laminin
      and heparan sulfate. Under these conditions, cultures could be maintained for
      several months, but pigmented cell cultures did not develop a measurable
      transepithelial resistance (TER), and the TER of non-pigmented cell cultures was
      typically only 20-30 omega cm2. Much higher TERs exceeding 200 omega cm2 could be
      measured from non-pigmented cell cultures 3-5 days after plating, but these high
      values were unstable. Examination of the cultures with electron microscopy
      revealed that the cells were partially differentiated with the formation of a
      basal lamina and intercellular junctions. Labelling with a specific monoclonal
      antibody marker for tight junction protein (ZO-1) suggested that non-pigmented
      cell cultures showed extensive tight junction formation. The low TER of the non
      pigmented cell cultures appears therefore not to be due to the lack of tight
      junctions but rather to the presence of spaces between cells.

PMID- 7506671
TI  - Kinetic response of human marrow myeloid progenitor cells to in vivo treatment of
      patients with granulocyte colony-stimulating factor is different from the
      response to treatment with granulocyte-macrophage colony-stimulating factor.
AB  - We previously demonstrated that granulocyte-macrophage colony-stimulating factor
      (GM-CSF) induced sustained increases in cycling of myeloid progenitors in
      patients with sarcoma. However, decreased proliferation of these cells to a slow-
      or noncycling state, below pretreatment levels, occurred within 1 to 2 days and
      maintained for at least 1 week after discontinuation of GM-CSF. To assess
      possible biological differences in GM-CSF and granulocyte (G)-CSF in such kinetic
      effects, we evaluated cycling status of marrow progenitors before, during, and
      after administration of recombinant human G-CSF (5 micrograms/kg/d subcutaneously
      [s.c.]) to six patients with sarcoma for 8 days. On the last (8th) day of G-CSF
      treatment, cycling rates of colony-forming units-granulocyte/macrophage (CFU-GM),
      burst-forming units-erythroid (BFU-E), and multipotent colony-forming units (CFU
      GEMM) were enhanced 1.5- to 1.9-fold, to values of 40 +/- 10% to 58 +/- 5%. In
      sharp contrast to patients receiving GM-CSF, however, progenitor cells from
      patients off G-CSF treatment for 2 to 4 days were still rapidly proliferating.
      These differences in proliferative kinetics may be of use for design of clinical
      trials to efficaciously utilize these growth factors.

PMID- 7506672
TI  - Decreased production of cytokines after cytomegalovirus infection of marrow
      derived stromal cells.
AB  - Cytomegalovirus (CMV) infection is frequently associated with graft failure in
      bone marrow transplant patients; the pathogenesis of this myelosuppression in not
      clearly understood. We have previously documented that CMV-induced
      myelosuppression is related to an alteration of the marrow microenvironment. To
      further investigate the effect of CMV on stromal cell function, conditioned media
      (CM) from CMV-infected or uninfected stromal cells were tested for their capacity
      to promote the growth of granulocyte/macrophage colony-forming cells (CFU-GM) and
      for their concentration in colony-stimulating factors (CSFs) such as interleukin
      3 (IL-3), IL-6, granulocyte-macrophage and granulocyte colony-stimulating factors
      (GM-CSF and G-CSF). CM from CMV-infected stromal cells failed to sustain
      granulocyte-macrophage colony-forming unit (CFU-GM) growth. The production of IL
      6, GM-CSF, and G-CSF, measured by enzyme-linked immunosorbent assay (ELISA), was
      21,150 +/- 3392, 57 +/- 15, and 2340 +/- 717 pg/mL, respectively, in CMV-infected
      stromal cells stimulated by lipopolysaccharide (LPS) and was significantly
      decreased (p < 0.01) from the control values (177,138 +/- 98,692, 113 +/- 20, and
      5533 +/- 1306 pg/mL). These results suggest that the myelosuppressive effect of
      CMV is primarily due to a lack of CSF production. To further document this
      hypothesis, primitive marrow progenitor cells (blast colony-forming cells [Bl
      CFC]) cultured on CMV-infected stromal layer have been grown in the presence of
      IL-3 (20 ng/mL), IL-6 (20 ng/mL), GM-CSF (40 ng/mL), and G-CSF (50 ng/mL). Used
      alone, all these CSFs partially reverse the CMV-induced inhibition of Bl-CFC
      growth; the combination of these CSFs completely restores normal Bl-CFC values.
      These data strongly suggest that CMV-induced myelosuppression is related to the
      lack of CSF production by the cells of the marrow microenvironment.

PMID- 7506673
TI  - Mast cell growth factor enhances multilineage hematopoietic recovery in vivo
      following radiation-induced aplasia.
AB  - Based on in vitro studies, mast cell growth factor (MGF; also known as steel
      factor, stem cell factor, and c-kit ligand) has been implicated as an important
      hematopoietic regulator, especially in the presence of additional hematopoietic
      cytokines. Since hematopoietic regeneration follows sublethal radiation-induced
      hematopoietic injury and is thought to be mediated by endogenously produced
      cytokines, the ability to accelerate recovery from radiation-induced
      hematopoietic hypoplasia was used to evaluate in vivo effects of MGF
      administration. Female B6D2F1 mice were exposed to a sublethal 7.75-Gy dose of
      60Co radiation followed by subcutaneous administration of either saline or 100,
      200, or 400 micrograms/kg/d recombinant murine MGF on days 1 to 17
      postirradiation. Recoveries of bone marrow and splenic spleen colony-forming
      units (CFU-S), granulocyte-macrophage colony-forming cells (GM-CFC), and
      peripheral white blood cells (WBC), red blood cells (RBC), and platelets (PLT)
      were determined on days 14 and 17 during the postirradiation recovery period. MGF
      accelerated hematopoietic recovery at the 100 and 200 micrograms/kg/d doses. The
      100 micrograms/kg/d dose accelerated recovery of only GM-CFC, while the 200
      micrograms/kg/d dose accelerated CFU-S, GM-CFC, WBC, and PLT recoveries. In
      contrast, hematopoietic recovery was delayed in mice receiving the 400
      micrograms/kg/d dose. These studies demonstrate the in vivo dose-dependent
      ability of MGF to accelerate multilineage hematopoietic regeneration following
      radiation-induced hematopoietic hypoplasia. They also document detrimental
      effects of providing "supraoptimal" doses of this growth factor and suggest
      caution in dose-escalation trials in humans.

PMID- 7506674
TI  - Inhibition of erythroid differentiation by stem cell factor in K562 cells
      expressing the c-kit gene.
AB  - We found a K562 subclone (K562YO) that highly expressed the c-kit gene. K562YO
      had a higher capability of erythroid differentiation by hemin and cytosine
      arabinoside (Ara-C) than its parent K562 (KIT-). We obtained the transfectant
      expressing c-kit by introducing c-kit cDNA into K562 (KIT-). The differentiation
      of the transfectant was similar to that of the parent cell. Thus the difference
      described above was not due to the expression of c-kit. Next, we investigated the
      effects of stem cell factor (SCF) on the differentiation of the K562 cell
      expressing c-kit. SCF did not enhance the cell growth of K562YO. On the other
      hand, SCF suppressed induction of benzidine-positive cells when c-kit-positive
      cells were treated with hemin and Ara-C, especially at a low concentration.
      Furthermore, c-kit mRNA and protein were down-regulated during erythroid
      differentiation. SCF also downregulated the c-kit proteins. Our results suggest
      that the SCF/c-kit signals could act negatively for erythroid differentiation of
      the K562 cells expressing c-kit. K562YO is also useful for studying the mechanism
      that controls the expression of the c-kit gene because there is a K562
      counterpart cell line that does not express this gene.

PMID- 7506675
TI  - Priming with recombinant human hematopoietic cytokines before bone marrow harvest
      expands in vivo and enhances ex vivo recovery of myeloid progenitors in short
      term liquid cultures.
AB  - BACKGROUND AND AIM: Short-term liquid marrow cultures (STLMC) are a potential
      source for autografting. We have previously shown that the quality of such grafts
      from transplantation candidates may be improved by hematopoietic cytokine
      support, especially if purified CD34-positive progenitors are cultured. The aim
      of this preclinical work was to quantitate ex vivo recovery of myeloid
      progenitors (colony-forming units-granulocyte/macrophage [CFU-GM]) in STLMC
      before and after short-term, in vivo treatment with recombinant human granulocyte
      colony-stimulating factor (rhG-CSF), granulocyte-macrophage colony-stimulating
      factor (rhGM-CSF), or interleukin-3 (rhIL-3). EXPERIMENTAL SETUP: Twenty-two
      sequential patients in marrow remission for hematological malignancies and
      eligible for autologous marrow transplantation received rhG-CSF or rhGM-CSF for 5
      days or rhIL-3 for 10 days before marrow harvest. Marrow samples before and after
      in vivo priming were studied for CFU-GM in pre- and post-STLMC. RESULTS: After
      priming with rhG-CSF, rhGM-CSF, or rhIL-3, the number of isolated light-density
      cells increased nine-, six-, and two-fold, respectively. The total number of
      sampled (18 mL marrow) myeloid progenitors preculture (day 7/14 CFU-GM x 10(4)
      increased significantly from median 0.7/1.1 before to 37.3/26.7 after priming
      with rhG-CSF (n = 8) and from 5.6/3.4 before to 46.6/44.9 after priming with rhGM
      CSF (n = 8) but remained unchanged (3.7/1.5 to 3.6/5.7) after priming with rhIL-3
      (n = 6). The number of myeloid progenitors postculture (day 7/14 CFU-GM x 10(4)
      per 18 mL marrow) in cytokine-supported STLMC significantly increased from median
      0.3/0.6 before to 7.0/5.3 after priming with rhG-CSF and from 1.9/1.6 before to
      24.4/14.4 after priming with rhGM-CSF but remained unchanged (0.4/0.6 to 0.4/0.2)
      after priming with rhIL-3. Cytokine-primed and purified CD34+ marrow cells may be
      expanded in STLMC by a cytokine-driven differentiation into late myeloid
      progenitors and endstage cells. CONCLUSION: In vivo priming of bone marrow cells
      by hematopoietic cytokines significantly increases the recovery of harvested pre-
      and postculture myeloid progenitors. During cytokine-supported STLMC, early
      myeloid progenitors may differentiate into a "very late" progenitor pool with a
      potential for fast marrow regeneration. The number of such progenitors in
      cytokine-supported short-term liquid cultures may be sufficient for fast myeloid
      engraftment and complete peripheral blood or marrow stem-cell support after high
      dose chemotherapy.

PMID- 7506676
TI  - Conserved HisVI-17 of the NK-1 receptor is involved in binding of non-peptide
      antagonists but not substance P.
AB  - Residue number 17 in transmembrane segment VI has been shown to be crucial for
      the binding of agonists in G-protein-coupled receptors for the monoamines. In
      many peptide receptors a histidyl residue has been conserved at this position. We
      find that replacement of HisVI-17 in the NK-1 receptor with either glutamine,
      phenylalanine, or alanine has no apparent effect on the binding of the natural
      peptide ligand substance P or on the agonist induced increase in
      inositolphosphate turnover. However, the binding of certain non-peptide
      antagonists was impaired; for example, replacement of HisVI-17 with alanine
      decreased the affinity for FK888 and RP67,580 5- to 12-fold, respectively. A
      glutamine side chain was a good substitute for the imidazole in the binding of
      all non-peptide antagonists. It is concluded that the conserved HisVI-17 in the
      NK-1 receptor is involved in the binding of certain non-peptide antagonists, but
      is not important for the action of the natural peptide agonist, substance P.

PMID- 7506677
TI  - Evidence for the existence of hyaluronectin-binding proteins in the plasma
      membranes.
AB  - This report documents for the first time the existence of specific binding
      proteins for hyaluronic acid binding protein (hyaluronectin) in the plasma
      membranes of normal and transformed cells. Firstly, we showed the specific
      binding of hyaluronic acid binding protein to the cell surface of normal rat
      heart fibroblasts (NRHF) by saturation and competition methods using 125I-labeled
      hyaluronic acid binding protein and calculated the binding dissociation constant
      (0.43 x 10(-13) M). In order to identify hyaluronectin-binding protein on the
      cell surface, plasma membranes isolated from rat brain, liver and fibrosarcoma
      were separated by SDS-PAGE and transferred to nitrocellulose paper by
      electroblotting. Incubation of the transferred membrane proteins with 125I
      labeled hyaluronectin in the presence of non-ionic as well as ionic detergents
      revealed two prominent bands of approximate molecular mass of 37 kDa and 40 kDa
      in brain, liver and fibrosarcoma. The specificity of the binding
      [125I]hyaluronectin to 37-kDa and 40-kDa membrane proteins was further confirmed,
      as the intensity of the bands was reduced in the presence of a 20-fold excess of
      unlabeled hyaluronectin. We discuss our observations on hyaluronectin-binding
      membrane proteins in the context of hyaluronectin-mediated cellular functions.

PMID- 7506678
TI  - Topology of Na,K-ATPase alpha subunit epitopes analyzed with oligopeptide
      specific antibodies and double-labeling immunoelectron microscopy.
AB  - Using four oligopeptide-specific polyclonal antibodies, we mapped the alpha
      subunit of Na,K-ATPase by double-labeling immunoelectron microscopy combined with
      negative staining. The results show that the epitopes of the N-terminus (Gly1
      His13), C-terminus (Ile1002-Tyr1016) and Leu815-Gln828 are located on the same
      face of crystallized Na,K-ATPase membranes from pig kidney, whereas the epitope
      Asn889-Gln903 is present on the opposite side. The present study demonstrates the
      cytoplasmic location of C-terminus and that Leu815-Gln828 is exposed on the
      cytoplasmic and Asn889-Gln903 on the extracellular side. The results are
      consistent with an eight- or ten-segment model, and support the existence of an
      M5/M6 loop and the presence of one transmembrane segment between Leu815-Gln828
      and Asn889-Gln903.

PMID- 7506679
TI  - Importance of Arg-219 for correct biogenesis of alpha 1 homooligomeric glycine
      receptors.
AB  - The inhibitory glycine receptor is characterized by a pentameric arrangement of
      subunits with four predicted transmembrane segments (M1-M4) each. Here, we have
      mutagenized arginine residues located at both termini of the alpha 1 subunit
      segment, M2, which lines the receptor's anion channel. No glycine-gated channel
      formation could be detected in the plasma membrane of expressing cells for any of
      the mutants. In addition, mutating the arginine at the cytoplasmic terminus of M2
      (R219) generated proteins which were only core-glycosylated, retained within
      intracellular compartments, and aggregated to high molecular weight complexes.
      Thus, residue R219, which corresponds to an arginine/lysine conserved in other
      ligand-gated ion channel polypeptides, is essential for correct biogenesis of the
      receptor.

PMID- 7506681
TI  - General practitioners' strategies and tactics of communication with the
      terminally ill.
AB  - Interviews with 22 randomly selected general practitioners (GPs) investigated
      their communication with terminally ill patients. In interview analysis a
      conceptual distinction was drawn between objectives, strategies and tactics. When
      treating terminal patients, GPs expressed the objectives of keeping the patient
      comfortable, painfree, happy and maintaining dignity. A strategy is a plan and
      mode of approaching patients existing over an extended time period. Three
      strategies were described by GPs for use when interacting with terminally ill
      patients. These are characterized as 'try to disclose', 'let the patient decide'
      and 'avoid disclosing'. Tactics refer to behaviours used within a single
      consultation, as part of a strategy. Six tactics are described: evasion, denial,
      uncertainty, hints and prompts, euphemism and reassurance. Different strategies
      imply quite different forms of consultation. Thus to understand a consultation we
      must place it into the context of the series.

PMID- 7506680
TI  - Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid
      carriers and complement factors induced by oral contraceptives.
AB  - Three low-dose oral contraceptives Trinordiol, Gynatrol, and Marvelon, containing
      ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg),
      monophasic levonorgestrel, and monophasic desogestrel (DGS), respectively, were
      given to 65 healthy women, n = 21-22 in each group. Blood levels of antithrombin
      III (AT III), alpha 2-macroglobulin (alpha 2M) alpha 1-antitrypsin (alpha 1at),
      complement factors (factor B, C3, C4), pregnancy zone protein (PZP),
      corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) and
      albumin were measured before treatment and during the first and third treatment
      cycles. AT III levels decreased and alpha 1at levels increased in all three
      groups during treatment. alpha 2M increased during cycle 3 in the Trinordiol and
      Gynatrol groups. CBG, PZP and SHBG levels increased in all 3 groups, the CBG and
      PZP increase being higher in the Marvelon group than in the Gynatrol group.
      Increases in SHBG levels were found in the order Marvelon > Trinordiol >
      Gynatrol. Plasma levels of complement factors B, C3 and C4 remained unchanged. It
      is concluded that the increase in alpha 1at partly compensates for the fall in AT
      III, that the rise in PZP presumably enhances fibrinolysis, and that LNg has
      higher anti-estrogenicity and androgenicity than DSG.

PMID- 7506682
TI  - Growth hormone receptors in avian epiphyseal growth-plate chondrocytes.
AB  - Growth hormone receptor (GH-R) gene expression was evaluated in avian growth
      plate cartilage by Northern blot and hybridization using the avian GH-R probe. A
      single transcript of approximately 5.2 kb was demonstrated in cultured growth
      plate chondrocytes as well as in growth-plate extracts. GH receptor gene
      expression was inhibited by chicken GH (cGH) in a dose- and time-dependent
      manner. Chicken GH was more potent in down-regulating the GH-R gene expression
      than hGH, but on the other hand cGH exhibited a lower affinity to avian
      chondrocytes receptor than did the human hormone. Addition of ascorbic acid to
      the culture media caused cell differentiation: induction of alkaline phosphatase
      activity and attenuation of collagen type II gene expression. No differences in
      the GH-R gene expression were observed in the nondifferentiated cells compared
      with the differentiated cells. Chicken GH did not form any complex with the
      purified hGH binding protein (hGHBP), did not bind to human lymphocytes GH
      receptor, and did not affect Nb2 cell proliferation. These systems represent
      somatogenic and lactogenic types of GH receptors, respectively. In summary, avian
      growth-plate chondrocytes in situ and in culture exhibit GH-R and these receptors
      are capable of binding GH. Thus, the failure of GH to affect avian chondrocytes'
      proliferation was not due to either the absence of receptors on the cell membrane
      or to a lack in its binding activity, but rather may be due to events farther
      downstream.

PMID- 7506683
TI  - Comparative study of IGFBP properties in toad and rat sera.
AB  - The levels of IGF-I have been simultaneously measured by radioimmunoassay in
      samples of the toad Bufo arenarum and of normal male Wistar rats. In addition,
      the different fractions of IGF-I binding proteins (IGFBP) and their binding
      properties have been identified by ligand blot and Scatchard analysis in the
      serum of both species. In the toad, we have measured levels of IGF-I (2.78 +/-
      0.48 ng/ml) similar to those previously reported in amphibians but far below
      those found in rats. IGFBP levels were estimated at 129 +/- 23 and 4249 +/- 321
      pg/ml in toad and rat serum samples. Two main IGFBP fractions of 30-34 kDa,
      accompanied by a minor component of 24 kDa and seldom by another of 40 kDa, were
      identified in toad serum. In rat serum--as already reported--three bands of 40,
      30, and 24 kDa were identified, the first being the main component and the last
      the minor one. The Scatchard analysis of a competitive binding assay showed two
      types of binding sites in toad serum: one of high affinity-low capacity (Ka1 =
      1.6 x 10(10) M-1; R1 = 1.2 x 10(-11) M) and another with low affinity-high
      capacity (Ka2 = 1.9 x 10(8) M-1; R2 = 1.9 x 10(-10) M). The percentage fraction
      of these binding sites occupied by IGF-I was 13.5%. The figures for K1 and K2
      were lower and those for R1 and R2 were higher in rat than in toad serum. The
      percentage fraction of occupied rat IGF binding sites was 3.6%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7506684
TI  - The distribution of immunoreactive FMRF-amide, neurotensin, and galanin in the
      brain and pituitary gland of three species of Xiphophorus from birth to sexual
      maturity.
AB  - This report seeks to extend the existing information on the relationship of
      regulatory neuropeptides to neuroendocrine and pituitary function through a
      longitudinal study of the distribution of FMRF-amide, galanin (GAL), and
      neurotensin (NT) in the brain and pituitary gland of three species of Xiphophorus
      from birth to sexual maturity. In the pituitary gland, immunoreactive (ir)-NT and
      -GAL were localized in the three regions of the adenohypophysis; ir-FMRF-amide
      was found in the neurohypophsis and in cells of the rostral pars distalis, but
      the immune reaction to this antisera in the pituitary was of very low intensity.
      Ir-GAL was found to colocalize with growth hormone, prolactin, and somatolactin
      in pituitary cells. In the brain, ir-GAL was found in the posterior nucleus
      lateralis tuberis (NLT), nucleus preopticus (NPO), and in the nucleus preopticus
      periventricularis (NPP). Ir-NT was localized in the anterior NLT. Ir-FMRF-amide
      was localized in the nucleus olfactoretinalis (NOR) where it was colocalized with
      gonadotropin releasing hormone, as well as in tracts that appeared to extend from
      the NOR, through the NPO and NPP, to the NLT. The NLT and the NOR have been
      previously implicated in the pituitary regulation of reproductive function. The
      above-cited localizations suggest that these peptides are involved in the
      neuroendocrine regulation of growth and reproduction in this genus.

PMID- 7506685
TI  - The phylogeny of the genus Yersinia based on 16S rDNA sequences.
AB  - The inter- and intrageneric relationships of the genus Yersinia were investigated
      by sequence analysis of the 16S rRNA gene. A stretch of approximately 1450
      nucleotides was sequenced from representatives of ten of the eleven validly
      described species. Phylogenetic analysis revealed that yersinae form a coherent
      cluster within the gamma subgroup of Proteobacteria. The intrageneric
      relationship was characterized by five sublines with Y. enterocolitica, Y.
      rohdei, and Y. ruckeri forming separate sublines each represented by a single
      species. A separate subline was formed by Y. pestis, Y pseudotuberculosis and Y.
      kristensenii, while Y. mollaretii, Y. intermedia, Y. bercovieri, Y. aldovae, and
      Y. kristensenii formed a fifth subline. The phylogenetic distinctness of the
      yersiniae sublines is compared to published phenotypic properties and results of
      DNA-DNA similarity studies.

PMID- 7506687
TI  - Recombinant RNA phage Q beta capsid particles synthesized and self-assembled in
      Escherichia coli.
AB  - The Escherichia coli RNA phage Q beta coat protein-encoding gene (C) was
      amplified from native Q beta RNA using a reverse transcription-PCR technique.
      Gene C contains sequences coding for both the 133-amino acid (aa) Q beta coat
      protein (CP) and the 329-aa read-through protein (A1) consisting of CP and an
      additional 196-aa C-terminal sequence, separated from CP within the C gene by an
      opal (UGA) stop codon. Primers ensuring the natural environment for gene C,
      especially within the ribosome-binding site, and supplying C with unique
      restriction sites at both ends have been prepared. An amplified 1062-bp PCR
      fragment was positioned under the control of the strong E. coli trp promoter
      (Ptrp) within a pGEM-derived plasmid. The synthesis of gene C products was
      confirmed electrophoretically and immunologically. An immunodiffusion test with
      anti-Q beta phage antibodies and electron microscopy evaluation of the purified
      recombinant products showed that when expressed, the Q beta C gene was
      responsible for high-level synthesis and correct self-assembly of Q beta CP
      monomers into capsids indistinguishable morphologically and immunologically from
      Q beta phage particles, which we plan to use as surface display vectors.

PMID- 7506686
TI  - Antibody engineering by parsimonious mutagenesis.
AB  - The human monoclonal antibody (humAb) problem has largely been solved with the
      aid of the polymerase chain reaction (PCR) [Larrick et al., Bio/Technology 7
      (1989a) 934-938; Larrick et al., Biochem. Biophys. Res. Commun. 160 (1989b) 1250
      1256; Chiang et al., BioTechniques 7 (1989) 360-366]. Phage display has now made
      it possible to recover humAb with primary response level affinities (approx.
      10(6) M-1) for virtually any antigen (including self antigens) from comprehensive
      libraries of B-cell repertoires from non-immunized humans [Marks et al., J. Mol.
      Biol. 222 (1991) 581-597; Marks et al., Bio/Technology 10 (1992) 779-783;
      Griffiths et al., EMBO J. 12 (1993) 725-734]. This means that the goal of
      therapeutic humAb without immunization is within reach. However, in order to
      achieve the affinities generally required for therapeutic use (> or = 10(9) M-1),
      reliable methods will be needed to complete the affinity maturation process in
      vitro. Available X-ray crystallographic data and energy calculations indicate
      that only a fraction of the substantial contact surface between the Ab and
      protein antigens contribute significantly to affinity. Thus, the remaining
      contact surface presents multiple opportunities to develop additional high
      affinity contacts, needing only a means to identify them. To this end, we have
      developed a computer-assisted method for oligodeoxyribonucleotide-directed
      scanning mutagenesis, called parsimonious mutagenesis (PM), whereby all three
      complementarity-determining regions (CDR) of a variable region (V-region) gene
      can be simultaneously and thoroughly searched for improved variants in libraries
      of manageable size. These libraries are made with low-redundancy 'doping' codons
      and biased nucleotide (nt) mixtures designed to maximize the abundance of
      combining sites with predetermined proportions of preselected sets of alternative
      amino acids (aa). This allows the library to 'probe' the surface of the antigen
      one or a few aa residues at a time with a wide selection of aa side chains to
      search out and identify new high-affinity contacts. In addition to affinity
      maturation in vitro, PM can also be used to remove unwanted cross-reactivities
      and to 'reshape' rodent mAb for human therapeutic use.

PMID- 7506688
TI  - A novel strategy for the immunological tagging of cDNA constructs.
AB  - We describe the construction of pBact-myc, an expression vector that incorporates
      an immunological 'tag' into the produced polypeptide. When transfected into
      recipient cell lines, tagged protein fragments derived from any source can be
      visualised using a single monoclonal antibody (mAb). The neuronal-associated
      protein 2c (MAP2c) was tagged with a sequence encoding a peptide from the human c
      myc gene. The preservation of normal function of the tagged protein was shown by
      transfecting it into cultured cell lines. No difference in binding ability to
      cellular microtubules could be observed between the myc-tagged MAP2c and the wild
      type forms, and both produced the same characteristic changes in microtubule
      organisation. This approach is being used to study the biological function of
      selected fragments of MAP2c and other MAP-encoding genes. The pBact-myc
      expression vector represents a fast and convenient way to produce tagged
      polypeptides of selected sequences encoding whole proteins or fragments, for the
      analysis of their function in living cells.

PMID- 7506689
TI  - Selection and design of high-affinity RNA ligands for HIV-1 Rev.
AB  - We have used in vitro selection to isolate minimal, high-affinity RNA ligands for
      the Rev protein of HIV-1. Sequence analysis reveals that the tightest binding
      aptamers exhibit some similarity to a Rev-binding element (RBE) localized within
      the Rev-responsive element (RRE), but also contain novel sequence and structural
      motifs. A short helical stem and bulged nucleotides (nt) CUC ... UYGAG that have
      no counterpart in the wild-type (wt) element contribute to high-affinity binding.
      We have designed and synthesized a short (37 nt) RNA molecule that incorporates
      this motif; this RNA ligand has from three- to fivefold tighter binding than the
      full-length wt element, and up to 16-fold tighter than minimal wt RBEs. A
      guanosine:guanosine pairing that is postulated to occur in the wt element has
      been altered to other base pairings in the context of our optimized minimal
      element. RNAs that contain non-Watson-Crick base pairings, that can be modeled as
      isosteric to the wt G:G pair, bind Rev up to 160-fold tighter than elements that
      contain canonical Watson-Crick pairings or non-isosteric mismatches. These
      results support the hypothesis that Rev recognizes structural features associated
      with a non-Watson-Crick base pair.

PMID- 7506690
TI  - In vitro evolution of functional nucleic acids: high-affinity RNA ligands of HIV
      1 proteins.
AB  - SELEX (Systematic Evolution of Ligands by EXponential enrichment) is a protocol
      for isolating, from a pool of variant nucleic acid sequences, high-affinity
      ligands to a target protein [Tuerk and Gold, Science 249 (1990) 505-510]. This
      procedure involves cycles of affinity selection by a target molecule from a
      heterogeneous population of nucleic acids, replication of the bound species (the
      ligands), and in vitro transcription to generate an enriched pool of RNA. We have
      used the SELEX procedure to obtain high-affinity RNA ligands against the reverse
      transcriptase and the Rev and Tat proteins of human immunodeficiency virus 1 (HIV
      1). Through sequence comparisons within the collection of ligands isolated for
      each of these target proteins, we derive consensus descriptions of what secondary
      structure and primary sequences are required for binding. These descriptions
      serve as the starting point for the ultimate development of compounds intended to
      alter the course of HIV-1 infection.

PMID- 7506691
TI  - Defining critical residues in the epitope for a HIV-neutralizing monoclonal
      antibody using phage display and peptide array technologies.
AB  - A peptide display library [Scott and Smith, Science 249 (1990) 386-390] was
      constructed that expressed 1.5 x 10(8) unique 20-amino-acid (aa) peptides fused
      to the N-terminus of the pIII coat protein of filamentous phage fd. This phage
      display library (PDL-20) was prepared using a degenerate oligodeoxyribonucleotide
      designed to minimize bias towards most aa. Characterization of the PDL-20 showed
      that all aa were present at the expected frequency and that there was no
      positional bias. Screening of this library with a HIV-1 isotype MN envelope
      reactive monoclonal antibody (mAb 58.2) using two different panning procedures
      showed that the biopanning technique was sensitive to one phage in 10(8).
      Analysis of peptide sequences from panning the mAb identified a core antibody
      recognition sequence of four aa residues (GPGR) and two preferred flanking
      residues on either side. This epitope occurred at various locations within the
      random aa segment demonstrating an absence of positional or nearest neighbor
      effects. Parallel panning experiments using an array of 266 synthetic peptides
      identified an epitope similar to that defined by the phage display library.

PMID- 7506692
TI  - Isolation and characterization of nucleic acid-binding antibody fragments from
      autoimmune mice-derived bacteriophage display libraries.
AB  - The display of antibody fragments (Fab) on the surface of filamentous
      bacteriophage and selection of phage that bind to a particular antigen has
      enabled the isolation of Fab with numerous specificities, including haptens,
      proteins and viral particles. We have examined the possibility of isolating
      nucleic acid-binding Fab by constructing a combinatorial library of phage
      displaying Fab derived from autoimmune (MRL/lpr) mice. Autoimmune mice were
      chosen because they contain antibodies (Ab) reactive against nuclear components,
      including DNA, RNA and protein complexes. The library was panned against single
      stranded (ss) calf thymus (CT) DNA and the selected Fabs were analyzed further.
      Characterization of the nucleic acid-binding phage led to the identification of
      two kinds of Fab with quite different properties. One Fab bound with high
      affinity a variety of ssDNA molecules, as well as several model RNA substrates.
      This Fab has been affinity purified to greater than 95% and competition studies
      revealed a marked preference for binding to poly(dT). The second Fab showed a
      reduced binding to RNA ligands and a restricted number of ssDNA molecules.
      Analysis of the deduced amino acid (aa) sequences of the Fab variable (V) regions
      revealed that the heavy (H) chain V region from the strong nucleic acid-binding
      Fab was derived from a VH gene that is used recurrently in autoantibodies. This
      VH domain was most similar to an anti-ssDNA autoimmune monoclonal antibody (mAb)
      suggesting that antigen-binding specificities present in an autoimmune repertoire
      may be directly accessed by this approach.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506693
TI  - Polycos vectors: a system for packaging filamentous phage and phagemid vectors
      using lambda phage packaging extracts.
AB  - A new class of hybrid vectors, 'polycos' vectors, incorporate a phage lambda cos
      site and filamentous phage origin to allow high-efficiency cloning via in vitro
      lambda packaging extracts. The head-filling mechanism of cos site recognition by
      lambda packaging proteins permits concatemers of several of these small cos
      containing vectors to be packaged per phage particle. Excision of vector monomers
      after infection is accomplished via a lambda ZAP-like M13 excision process. This
      system has the advantage of adapting high-efficiency lambda packaging extracts to
      M13 and phagemid cloning vectors.

PMID- 7506694
TI  - EPR spin trapping of free radicals produced by bleomycin and ascorbate.
AB  - In the presence of ascorbate, bleomycin (BLM) is converted to a redox-inactive
      form that is incapable of inducing DNA strand scission. We have employed EPR spin
      trapping with 5,5-dimethylpyrroline-1-oxide (DMPO) to examine free radical
      production during this process. The introduction of ascorbate to an Fe(III)BLM
      DMPO system results in the formation of three EPR observable free radicals. One
      of these radicals is the resonance-stabilized ascorbate free radical (aH = 1.8 G)
      that is not spin trapped by DMPO; the other two are the result of DMPO spin
      trapping. These radicals appear to be two carbon-centered radicals, DMPO/.CR1,
      (aN1 = 15.75 G, aH1 = 22.30 G, aN/aH = 0.706) and DMPO/.CR2 (aN2 = 15.20 G, aH2 =
      19.20 G, aN/aH = 0.79). Although it is not possible to identify the exact
      structures of the carbon-centered radicals that are spin trapped, the hyperfine
      splittings, as well as the aN/aH values, are characteristic of the presence of
      electron-withdrawing groups, such as the oxygen atom when attached to the carbon
      atom. In fact, these parameters are characteristic of DMPO spin trapping results
      obtained when sugars are subjected to oxidative insult from HO.. Thus, these BLM
      ascorbate produced radicals may well be derived from the sugar moiety of BLM.

PMID- 7506695
TI  - Expression of CD45RO on circulating CD19+ B-cells in Crohn's disease.
AB  - Crohn's disease is an immunoregulatory disorder of the intestine that can be
      associated with systemic manifestations. This study analysed B-cell
      differentiation antigens to identify B-cell subpopulations unique to patients
      with Crohn's disease. CD45 isoform expression was used as an indicator of B-cell
      differentiation stage. This work shows that B-cells in blood and gut of patients
      with Crohn's disease are at an advanced stage of differentiation based on their
      unusual presentation of transitional (RA+ RO+) and late stage (RO+)CD45 isoforms
      on lamina propria lymphocytes, whereas normal intestinal lamina propria
      lymphocytes B-cells express primarily CD45RA. Crohn's disease patients had
      heightened expression of the CD45RO isoform on CD19+ lamina propria lymphocytes,
      and was found in a statistically significant proportion of Crohn's peripheral
      blood mononuclear cells (PBMC) where CD19+ PBMC had an expression pattern
      affecting an unexpectedly high proportion of these differentiated or late stage
      CD45RO+ B-cells. The expression of CD45RO varied greatly among CD19+ PBMC from
      patients with Crohn's disease, so multiple regression analysis was performed
      between these CD45 isoforms and several clinical parameters. After grouping high
      and low CD45RO expression on CD19+ B-cells, a significant statistical difference
      was found between high Crohn's disease activity index (CDAI) and low CDAI Crohn's
      disease patients respectively.

PMID- 7506696
TI  - Angiotensinogen: an acute-phase protein?
AB  - Angiotensinogen has been assumed to be an acute-phase protein, because some forms
      of acute inflammation, eg, the injection of lipopolysaccharide or cellite or
      partial hepatectomy, increased the hepatic synthesis of angiotensinogen. In
      addition, the well-characterized nephrectomy-induced stimulation of
      angiotensinogen was thought to represent an acute-phase reaction. To evaluate
      this hypothesis, we examined changes in angiotensinogen secretion by the isolated
      perfused rat liver after the systemic administration of turpentine or
      lipopolysaccharide as well as in response to nephrectomy or sham nephrectomy.
      Comparison was made with the secretion of two typical acute-phase proteins, alpha
      1-acid glycoprotein and alpha 2-macroglobulin, and with the secretion of the
      negative acute-phase protein albumin. All forms of experimental surgery
      stimulated the secretion of both control acute-phase proteins several-fold. In
      contrast, the response of angiotensinogen was not uniform; lipopolysaccharide and
      bilateral nephrectomy stimulated secretion twofold to threefold, sham nephrectomy
      had no effect, and turpentine decreased the secretion to 30% of the control
      level. A similar inhomogeneity was found in an additional experiment performed to
      analyze the direct effects of interleukin-1 or interleukin-6 on the secretion of
      angiotensinogen by freshly isolated hepatocytes. Interleukin-6 increased but
      interleukin-1 decreased the mRNA and secretion of angiotensinogen, whereas both
      cytokines increased the secretion of both acute-phase proteins. Because of this
      nonuniform behavior of angiotensinogen, it is premature to classify
      angiotensinogen as an acute-phase protein until a specific function for
      angiotensinogen during acute inflammation is known.

PMID- 7506697
TI  - Modulation of renin-angiotensin and kallikrein gene expression in experimental
      hypertension.
AB  - Previous studies have shown that chronic low-dose administration of 40 ng/min
      angiotensin II by osmotic minipump to uninephrectomized rats mimics the temporal
      hypertensive response and the circulating angiotensin II levels observed in two
      kidney, one clip Goldblatt rats. Furthermore, renal tissue angiotensin II
      contents were higher than the circulating angiotensin II levels, suggesting that
      circulating angiotensin II induces endogenous intrarenal angiotensin II
      production. The present study examined the molecular mechanisms by which
      intrarenal angiotensin II production is modulated in angiotensin II-induced and
      two-kidney Goldblatt hypertension. Two weeks after clipping, intrarenal renin
      mRNA levels were elevated threefold in the clipped kidney of Goldblatt rats but
      were markedly suppressed in the nonclipped kidneys of Goldblatt rats (28% of
      control values) and in the remaining kidney of uninephrectomized angiotensin II
      infused rats (7% of control values). In contrast, there were sustained levels of
      angiotensinogen mRNA in the kidneys and livers of Goldblatt and angiotensin II
      infused rats, indicating differential regulation of the genes of the renin
      angiotensin system. Renal kallikrein gene expression was not altered in either of
      the hypertensive groups 14 days after the induction of hypertension, suggesting
      the absence of an enhanced counteracting kinin influence.

PMID- 7506698
TI  - Regulation of angiotensin II receptors in rat brain during dietary sodium
      changes.
AB  - Activation of the renin-angiotensin system by sodium deficiency is associated
      with reciprocal changes in the expression of angiotensin II receptors in adrenal
      glomerulosa and vascular smooth muscle cells. The effects of dietary sodium
      changes on the expression of brain angiotensin receptor subtype 1 (AT1) mRNAs
      were examined in rats maintained on normal, low, and high sodium intake for 3
      weeks. Plasma aldosterone and renin activity were elevated in rats maintained on
      a low salt diet compared with normal rats and were reduced in rats maintained on
      a high salt diet. These results are consistent with previous findings on the
      effects of altered dietary sodium on the renin-angiotensin system. The expression
      of AT1A and AT1B receptor subtype mRNAs was determined by quantitative reverse
      transcriptase-polymerase chain reaction during changes in sodium intake. The
      results revealed that sodium deprivation enhanced the expression of AT1B
      receptors in decorticated brains by 164% compared with high sodium intake.
      Conversely, high sodium diet increased the expression of AT1A receptors by 155%
      in the brain compared with low sodium intake. These data suggest that AT1A and
      AT1B receptors play reciprocal roles in central mechanisms for the control of
      fluid homeostasis. Further analysis of the molecular biology of angiotensin II
      receptor regulation in the brain may provide new insights into the interplay
      between the renin-angiotensin system and blood pressure regulation and also into
      the role of angiotensin II in the pathogenesis of essential hypertension.

PMID- 7506699
TI  - Insulin attenuates agonist-evoked calcium transients in vascular smooth muscle
      cells.
AB  - Insulin may decrease the contractile response of vascular smooth muscle to
      vasoactive agents. This could be due to interactions of insulin with the effects
      of vasoactive agonists on intracellular free calcium transients in vascular
      smooth muscle cells. This study assesses the effects of physiological doses of
      insulin (70 microU/mL) on calcium responses in cultured vascular smooth muscle
      cells (primary unpassaged and passaged) to angiotensin II (1 nmol/L), arginine
      vasopressin (10 nmol/L), and norepinephrine (10 mumol/L). Intracellular free Ca2+
      concentrations in single cells were measured microphotometrically using fura 2
      AM. Insulin, angiotensin II, arginine vasopressin, and norepinephrine
      significantly increased calcium (to 115 +/- 7, 183 +/- 20, 184 +/- 15, and 168 +/
      12 nmol/L, respectively, from basal calcium of 90 +/- 10 nmol/L). Insulin
      significantly attenuated the agonist-induced calcium responses. The effects of
      insulin were almost completely inhibited by diltiazem, staurosporine, calphostin
      C, and thapsigargin. In conclusion, insulin stimulates calcium transients but
      blunts agonist-mediated calcium rises in vascular smooth muscle cells. These
      responses are related to regulatory effects of insulin on cellular calcium
      homeostasis and may explain how insulin modulates vascular smooth muscle
      contraction.

PMID- 7506701
TI  - Papaverine hydrochloride: effects on HIV replication and T-lymphocyte cell
      function.
AB  - Papaverine hydrochloride (PAP) has previously been shown to have a potent
      inhibitory effect on the replication of viruses such as cytomegalovirus (CMV) and
      measles. In this report the effect of PAP on human immunodeficiency virus (HIV)
      replication and T lymphocyte cell function were examined. MT4 cells infected with
      HIV strain 3b were incubated with serial dilutions of PAP (1-30 microM). At
      selected times postinfection HIV replication was measured by reverse
      transcriptase activity (RT) or HIV p24 Ag. PAP significantly inhibited HIV
      replication by more than 99% at doses of 30 microM with an CD50 and ED50 of 32
      microM and 5.8 microM respectively. The mechanism of inhibition of HIV caused by
      PAP appeared independent form its ability to increase intracellular levels of
      cAMP and was not mediated via a direct effect on RT activity. To examine T cell
      function, peripheral blood mononuclear cells (PBMC) from normal donors were
      stimulated with phytohemagglutinin (PHA) or CMV Ag in the presence or absence of
      PAP (1-30 microM). At selected times proliferative response to PHA and CMV Ag
      were determined by [3H]thymidine uptake. In addition, interferon (IFN) gamma and
      interleukin 2 (IL2) response to mitogens were measured by radioimmunoassay (RIA).
      PAP enhanced PHA induced IFN production at doses of 1-10 microM and CMV Ag
      induced IFN production at doses of 1-3 microM. Higher doses were inhibitory. PAP
      did not affect IL-2 production or IL2 receptor expression and had an inhibitory
      effect on mitogenic responses.

PMID- 7506700
TI  - Expression of nitric oxide synthase by cytokines in vascular smooth muscle cells.
AB  - In cultured vascular smooth muscle cells, the baseline mRNA and protein levels of
      an inducible type of nitric oxide synthase were barely detectable. Interferon
      gamma, tumor necrosis factor-alpha, and interleukin-1 beta each markedly
      increased mRNA and protein levels of this enzyme in parallel with the production
      of nitrite, a stable oxidative metabolite of nitric oxide. Actinomycin D
      abolished the cytokine-induced increases in mRNA levels and nitrite production.
      Cycloheximide, which abolished the cytokine-induced increase in nitrite
      production, had no effect on the interferon-gamma-induced increase in mRNA levels
      but partially inhibited that induced by interleukin-1 beta and markedly inhibited
      that induced by tumor necrosis factor-alpha. Transforming growth factor-beta 1,
      which inhibited the interferon gamma-, interleukin-1 beta-, and tumor necrosis
      factor-alpha-induced nitrite production, did not affect the increases in mRNA
      levels caused by these cytokines. Transforming growth factor-beta 1, however,
      significantly inhibited the increase in protein levels caused by these cytokines.
      These findings suggest that interferon gamma directly induces the expression of
      the inducible nitric oxide synthase gene, whereas tumor necrosis factor-alpha and
      interleukin-1 beta induce it, at least in part, via the induction of intermediary
      protein(s), and that transforming growth factor-beta 1 inhibits cytokine-induced
      nitric oxide production by blocking the posttranscriptional synthesis of
      inducible nitric oxide synthase.

PMID- 7506702
TI  - Rapid cold fixation of tissue samples by microwave irradiation for use in
      electron microscopy.
AB  - A cold microwave irradiation procedure was developed to fix rapidly and stain
      various tissues and monolayers for electron microscopy. Because microwave
      stimulation always produces some heat, melting ice was used to maintain the
      temperature of the tissue samples, the fixative, and the staining solution at 0
      to 4 degrees C. The low temperature also reduced vapour formation, thus
      minimizing the risk of explosion. The microwave method shortened the total time
      of fixation and dehydration from the usual 3 h required by the conventional
      method to 65 min. After microwave fixation, the ultrastructural details of
      membranes and subcellular structures were excellent.

PMID- 7506703
TI  - Single cell analysis of the expression of a nuclear protein, SCIP, by fluorescent
      immunohistochemistry visualized with confocal microscopy.
AB  - A widely applicable method for the accurate quantification or semiquantification
      of macromolecules at the level of individual cells is described and validated;
      this is a method which may considerably facilitate the study of many biological
      processes. This method relies on measuring fluorescent emission in
      immunocytochemically labelled cells with a confocal microscope. Emission is
      related quantitatively to the level of the fluorophore by the combination of an
      analysis of the polarization of the fluorescent emission and fluorophore
      rationing methods. The method was applied to the study of the expression of the
      suppressed cyclic AMP-induced POU protein (SCIP) transcription factor in glial
      cells of the central nervous system. In particular, the method allowed the study
      of transcription factor expression in defined cells present in heterogeneous
      cultures and in cell types which cannot be isolated in sufficient numbers for
      biochemical analysis using conventional techniques.

PMID- 7506704
TI  - Identification of rabbit eosinophils and heterophils in cutaneous healing wounds.
AB  - The study of wound healing has traditionally used the rabbit as an experimental
      model. We have recently localized the production of the multifunctional cytokine,
      TGF-alpha, to eosinophils in rabbit skin wounds. It was evident that during the
      process of TGF-alpha localization, the distinction between the two granulocytic
      cell types, eosinophils and heterophils, was impossible by conventional
      histochemical techniques. This paper describes a rapid method to distinguish
      these two granulocytes by virtue of their endogenous peroxidases and differential
      resistance to blockade by inhibitors. In sections that have been blocked by
      hydrogen peroxide, the peroxidase substrate 3,3'-diaminobenzidine, together with
      nickel chloride (DAB-Ni), preferentially stained the cytoplasm of rabbit
      eosinophils while sparing those of heterophils. This selective DAB staining of
      rabbit eosinophil peroxidase in H2O2-blocked rabbit wounds was verified at the
      ultrastructural level by electron microscopy. We applied this technique to
      quantify eosinophil and heterophil infiltration into the 21-day rabbit cutaneous
      healing wound model. Heterophils were found infiltrated into all three layers of
      the wound (clot > granulation > base), but eventually all disappeared by day 21.
      As with the heterophils, eosinophils which had infiltrated into the clot and base
      of the wound had disappeared by day 21. Unlike the heterophils, eosinophils in
      the granulation layer of the wound continued to increase up to day 21. The
      continually increased and sustained presence of the eosinophils together with
      their demonstrated production of TGF-alpha, in the granulation layer of the
      healing would suggests that these cells play an important role in the
      organizational aspects of healing wounds.

PMID- 7506705
TI  - ANF decreases active sodium transport and increases alveolar epithelial
      permeability in rats.
AB  - Previous studies reported that atrial natriuretic factor (ANF) decreased lung
      edema in guinea pigs. To determine whether ANF protects against lung edema by
      increasing active Na+ transport and lung edema clearance, ANF (10(-7) M) was
      instilled into the air spaces (n = 5) or perfused through the pulmonary
      circulation (n = 5) of isolated perfused liquid-filled rat lungs. These animals
      were compared with five control rats and four rats having amiloride (10(-5) M)
      instilled into the air space. Amiloride reduced lung edema clearance by 65%,
      perfused ANF reduced lung edema clearance by 32%, and instilled ANF did not
      change edema clearance compared with responses in control rats after 70 min of
      experimental protocol. Passive Na+ movement increased by 91% with perfused ANF
      and by 52% with instilled ANF compared with that in control rats. Albumin flux
      from the perfusate into the air space increased in ANF-perfused lungs compared
      with control lungs (P < 0.05) but not when ANF or amiloride was instilled into
      the air spaces. These results suggest that ANF instilled into rat air spaces or
      perfused through the pulmonary circulation increases lung epithelial permeability
      and that ANF perfused through the pulmonary circulation decreases lung edema
      clearance due to impaired active Na+ transport. Conceivably, the previously
      observed protective effect of ANF was due to reduced pressures across the
      pulmonary circulation, which resulted in less edema formation.

PMID- 7506706
TI  - Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and
      systemic blood pressure.
AB  - It has been suggested that chronic hypoxic pulmonary hypertension results from
      chronic hypoxic inhibition of endothelium-derived relaxing factor (EDRF)
      synthesis. We tested this hypothesis by studying whether chronic EDRF inhibition
      by N omega-nitro-L-arginine methyl ester (L-NAME) would induce pulmonary
      hypertension similar to that found in chronic hypoxia. L-NAME (1.85 mM) was given
      for 3 wk in drinking water to rats living in normoxia or hypoxia. Unlike chronic
      hypoxia, chronic L-NAME treatment did not increase pulmonary arterial pressure.
      Cardiac output was reduced and mean systemic arterial pressure was increased by
      chronic L-NAME treatment. The vascular pressure-flow relationship in isolated
      lungs was shifted toward higher pressures by chronic hypoxia and, to a lesser
      degree, by L-NAME intake. In isolated lungs, vasoconstriction in response to
      angiotensin II and acute hypoxia and vasodilation in response to sodium
      nitroprusside were increased by chronic L-NAME treatment in normoxia and chronic
      hypoxia. Chronic hypoxia, but not L-NAME, induced hypertensive pulmonary vascular
      remodeling. Chronic supplementation with the EDRF precursor L-arginine did not
      have any significant effect on chronic hypoxic pulmonary hypertension. We
      conclude that the chronic EDRF deficiency state, induced by L-NAME, does not
      mimic chronic hypoxic pulmonary hypertension in our model. In addition, EDRF
      proved to be less important for basal tone regulation in the pulmonary than in
      the systemic circulation.

PMID- 7506709
TI  - Dual function of tenascin: simultaneous promotion of neurite growth and
      inhibition of glial migration.
AB  - The extracellular matrix molecule tenascin is expressed within the developing
      peripheral nervous system, first by migrating neural crest cells and later by
      satellite (Schwann precursor) cells at the growing tips of peripheral nerves.
      Here we found that the neurite promoting activity of tenascin for sensory neurons
      is developmentally regulated: very young sensory ganglia of stage 23 (4 days old)
      embryos grew neurites on tenascin as fast as on laminin and fibronectin. The
      growth response of older (day 7 and 9) ganglia on laminin and fibronectin was
      similar to that of 4-day-old ganglia, while on tenascin neurite growth occurred
      only after a lag phase and at a slower rate. Neurite growth on tenascin was
      inhibited by antibodies to beta 1 integrin and by heparin. While tenascin
      promotes neurite outgrowth of peripheral neurons, we found that it does not allow
      satellite cell migration when it is present on the substratum, and it inhibits
      migration of satellite cells on fibronectin when added in soluble form. In
      contrast, soluble tenascin did not significantly alter the rate of neurite growth
      on tenascin, fibronectin or laminin substrata, although neurites were straighter
      and less attached. When isolated satellite cells were added to neurites grown on
      tenascin, they preferentially adhered to and elongated along neurite surfaces.
      Using patterned substrata of tenascin versus fibronectin or laminin confirmed
      that tenascin borders allow neurites to pass but act as barriers to migrating
      satellite cells. We postulate that tenascin or related molecules with dual
      functions in cell adhesion are important for peripheral nerve morphogenesis.
      Tenascin allows axonal growth, but may restrict random satellite cell migration
      into the fibronectin-rich mesenchyme, thereby inducing the compaction of nerve
      fascicles.

PMID- 7506707
TI  - Structural requirements of Bacillus subtilis small cytoplasmic RNA for cell
      growth, sporulation, and extracellular enzyme production.
AB  - Bacillus subtilis small cytoplasmic RNA (scRNA; 271 nucleotides) is a member of
      the signal recognition particle (SRP) RNA family, which has evolutionarily
      conserved primary and secondary structures. The scRNA consists of three domains
      corresponding to domains I, II, and IV of human SRP 7S RNA. To identify the
      structural determinants required for its function, we constructed mutant scRNAs
      in which individual domains or conserved nucleotides were deleted, and their
      importance was assayed in vivo. The results demonstrated that domain IV of scRNA
      is necessary to maintain cell viability. On the other hand, domains I and II were
      not essential for vegetative growth but were preferentially required for the RNA
      to achieve its active structure, and assembled ribonucleoprotein between Ffh and
      scRNA is required for sporulation to proceed. This view is highly consistent with
      the fact that the presence of domains I and II is restricted to sporeforming B.
      subtilis scRNA among eubacterial SRP RNA-like RNAs.

PMID- 7506708
TI  - An Azorhizobium caulinodans ORS571 locus involved in lipopolysaccharide
      production and nodule formation on Sesbania rostrata stems and roots.
AB  - Azorhizobium caulinodans ORS571 is able to nodulate roots and stems of the
      tropical legume Sesbania rostrata. An ORS571 Tn5 insertion mutant, strain ORS571
      X15, had a rough colony morphology, was nonmotile, and showed clumping behavior
      on various media. When this pleiotropic mutant was inoculated on roots or stems
      of the host, no nodules developed (Nod-). Compared with the wild type, strain
      ORS571-X15 produced lipopolysaccharides (LPS) with an altered ladder pattern on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels, suggestive of a
      different O-antigen structure with a lower degree of polymerization. A cosmid
      clone, pRG20, that fully complemented all phenotypes of ORS571-X15 was isolated.
      With a 6-kb EcoRI subfragment of pRG20, clumping was relieved and nodulation was
      almost completely restored, but the strain was still nonmotile. LPS preparations
      from these complemented strains resembled the wild-type LPS, although minor
      quantitative and qualitative differences were evident. The sequence of the locus
      hit by the Tn5 in ORS571-X15 (the oac locus) revealed a striking homology with
      the rfb locus of Salmonella typhimurium, which is involved in O-antigen
      biosynthesis. The Tn5 insertion position was mapped to the oac3 gene, homologous
      to rfbA, encoding dTDP-D-glucose synthase. Biochemical assaying showed that
      ORS571-X15 is indeed defective in dTDP-D-glucose synthase activity, essential for
      the production of particular deoxyhexoses. Therefore, it was proposed that the O
      antigen of the mutant strain is devoid of such sugars.

PMID- 7506710
TI  - Modulation of platelet-derived growth factor receptor expression in microvascular
      endothelial cells during in vitro angiogenesis.
AB  - Microvascular endothelial cells in vivo exhibit a plastic phenotype, forming a
      nonproliferative, differentiated capillary network, while retaining their ability
      to respond to injury by proliferation, migration and neovascularization. The
      presence of PDGF receptors and PDGF responsiveness in microvascular endothelial
      cells and the significance of PDGF isoforms in the control of endothelial cell
      growth and differentiation remain controversial. Since culture of microvascular
      endothelial cells in a three-dimensional (3D) system induced cell differentiation
      and angiogenesis and inhibited proliferation, the present study investigates the
      role of different extracellular matrix environments in inducing different
      microvascular endothelial cell phenotypes on microvascular endothelial cell PDGF
      receptor expression and PDGF responsiveness. In conventional two-dimensional (2D)
      culture, microvascular endothelial cells expressed both PDGF receptor alpha and
      beta chains. Suramin treatment demonstrated continuous downregulation of the
      alpha receptor surface expression. PDGF BB and, to a lesser extent, PDGF AB were
      mitogenic in 2D-culture, PDGF AA failed to induce any proliferative response
      despite inducing receptor autophosphorylation. During in vitro angiogenesis
      induced by 3D-culture, both PDGF receptors were rapidly downregulated. Assessment
      of cell proliferation showed quiescent cells and PDGF unresponsiveness. We
      conclude that the induction of a differentiated phenotype during in vitro
      angiogenesis (tube formation) driven in part by the spatial organization of the
      surrounding matrix is associated with a downregulation of PDGF receptors.
      Identification of the molecular cell-matrix interactions involved in this
      receptor regulation may allow for targeted manipulation of cell growth in vivo
      and lead to novel therapeutic applications for PDGF.

PMID- 7506711
TI  - Estradiol enhances leukocyte binding to tumor necrosis factor (TNF)-stimulated
      endothelial cells via an increase in TNF-induced adhesion molecules E-selectin,
      intercellular adhesion molecule type 1, and vascular cell adhesion molecule type
      1.
AB  - Adhesion of leukocytes to endothelial cells is a critical step in the development
      of acute and chronic inflammatory lesions. We report here that estradiol
      treatment of cultured human umbilical vein endothelial cells stimulated up to a
      twofold increase in TNF-induced adhesion of both polymorphonuclear leukocytes and
      PMA-activated peripheral blood mononuclear cells. This effect was more evident
      (threefold increase) when endothelial cells were cultured on the basement
      membrane glycoprotein laminin. Progesterone, but not testosterone, had a similar
      stimulatory effect. Estradiol also promoted a slight increase in interferon gamma
      stimulated endothelial cell adherence for peripheral blood mononuclear cells, but
      no effect of estradiol was observed when adhesion of leukocytes to endothelial
      cells was stimulated with IL-1 or IL-4. The estradiol-induced increase in
      leukocyte binding to human umbilical vein endothelial cells was partially blocked
      by antibodies to the adhesion molecules E-selectin, intercellular adhesion
      molecule type 1 (ICAM-1), and vascular cell adhesion molecule type 1 (VCAM-1).
      Indirect immunofluorescence techniques showed that estradiol produces an increase
      in TNF-induced cell surface expression of these molecules. Northern blot analysis
      demonstrated a transient increase in TNF-induced expression of mRNA for E
      selectin, ICAM-1, and VCAM-1 in endothelial cells treated with estradiol. Our
      data demonstrate that estradiol has important regulatory functions in promoting
      leukocyte-endothelial cell interactions that might contribute to the observed
      predominance in females of some autoimmune inflammatory diseases.

PMID- 7506712
TI  - Impaired nitric oxide-dependent cyclic guanosine monophosphate generation in
      glomeruli from diabetic rats. Evidence for protein kinase C-mediated suppression
      of the cholinergic response.
AB  - Nitric oxide (NO)-dependent cyclic guanosine monophosphate (cGMP) generation was
      examined in glomeruli isolated from 1-2-wk and 2-mo streptozotocin diabetic (D)
      and control (C) rats. After 1-2 wk of diabetes, ex vivo basal cGMP generation and
      cGMP responses to carbamylcholine (CCh) were significantly suppressed in
      glomeruli from D compared with those from C, whereas cGMP responses to the
      calcium ionophore A23187 and nitroprusside (NP) did not differ in glomeruli from
      D vs. those from C. After 2 mo, glomeruli from D did not respond to CCh, and
      responses to A23187 and NP were suppressed compared with those from C.
      Differences in basal, CCh, and A23187-responsive cGMP between D and C were
      abolished by the NO synthetase inhibitor NG-monomethyl-L-arginine. Soluble
      glomerular guanylate cyclase prepared from either D or C responded
      indistinguishably to NP, suggesting a role for NO quenching in the suppression of
      cGMP in intact glomeruli from D. Compared with those from C, glomeruli isolated
      from D demonstrated increased generation of thromboxane A2 (TXA2) and activation
      of protein kinase C (PKC). Both the TXA2/endoperoxide receptor antagonist Bay
      U3405 and inhibitors of PKC activity restored a cGMP response to CCh in glomeruli
      from D. Conversely, in glomeruli from C, the TXA2/endoperoxide analogue U46619
      activated PKC and suppressed the cGMP response to CCh. Both of those actions were
      blocked by inhibitors of PKC. The results indicate a progressive impairment of NO
      dependent cGMP generation in glomeruli from D which may be mediated in part by
      TXA2 and activation of PKC. This impairment may participate in glomerular injury
      in diabetes.

PMID- 7506713
TI  - Localization of cystic fibrosis transmembrane conductance regulator mRNA in the
      human gastrointestinal tract by in situ hybridization.
AB  - We have used in situ hybridization to localize expression of the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene in the human gastrointestinal
      tract and associated organs. The stomach exhibits a low level of CFTR expression
      throughout gastric mucosa. In the small intestine, expression is relatively high
      in the mucosal epithelium, with a decreasing gradient of expression along the
      crypt to tip axis. The cells of the Brunner's glands express high levels of CFTR
      mRNA. In addition, there is a small subpopulation of highly positive cells
      scattered along the epithelium in the duodenum and jejunum, but not in the ileum.
      These cells do not represent endocrine cells, as determined by lack of
      colocalization with an endocrine-specific marker. The distribution of CFTR mRNA
      in the colon is similar to the small intestine, with highest level of expression
      in the epithelial cells at the base of the crypts. In the pancreas, CFTR is
      expressed at high levels in the small, intercalated ducts and at lower levels in
      the interlobular ducts. CFTR transcripts are expressed at uniformly high levels
      in the epithelium of the gallbladder. Throughout the gastrointestinal tract, CFTR
      expression is increased in mucosal epithelial cells that are near lymph nodules.

PMID- 7506714
TI  - New antiserum against Ki-67 antigen suitable for double immunostaining of
      paraffin wax sections.
AB  - AIMS: To prepare a rabbit antiserum equivalent to MIB 1 to permit the
      simultaneous assessment of cell proliferation and other markers of interest using
      double labelling studies. METHODS: Rabbits were immunised with a synthetic
      peptide deduced from the cDNA sequence coding for the Ki-67 antigen. Serum
      samples were tested for immunoreactivity using different immunobiochemical
      methods. RESULTS: A polyclonal antiserum was derived which detects the native as
      well as recombinant parts of the Ki-67 antigen in different test systems.
      Furthermore, the antiserum stains the Ki-67 antigen in routinely processed,
      paraffin wax embedded material. CONCLUSIONS: After antigen unmasking by microwave
      treatment the antiserum described here represents a powerful tool for the
      determination of growth fractions even in archival material. It is especially
      suitable for double staining experiments in combination with monoclonal
      antibodies.

PMID- 7506715
TI  - Diencephalic gustatory connections in the channel catfish.
AB  - Vertebrate gustatory systems include a tertiary ascending pathway from a
      secondary gustatory nucleus in the hindbrain to several forebrain nuclei. This
      connection is prominent in catfish, corresponding to their highly developed sense
      of taste. Iontophoretic injections of horseradish peroxidase were used to
      identify the specific target nuclei of the tertiary gustatory pathway in channel
      catfish and to characterize those nuclei by their respective connections.
      Efferents from the secondary gustatory nucleus (nGS) ascend in the tertiary
      gustatory tract to the caudal inferior lobe, where they terminate caudally in the
      nucleus lobobulbaris (nLB) and nucleus centralis (nCLI), and rostrally in the
      nucleus diffusus (nDLI). Secondary projections from the facial lobe (FL) also
      terminate in the nLB and in the nucleus subglomerulus (nSG). The nLB forms three
      cell groups (caudal--nLB, rostrolateral--rl nLB, parvicellular--nLBp), which
      project to the facial lobe, vagal lobe, and telencephalon, respectively. Cells
      from the nCLI project throughout the caudal inferior lobe and to the
      acousticolateral torus semicircularis and telencephalon, while the nDLI and nSG
      have intrinsic connections within the inferior lobe. The lateral thalamic nucleus
      projects from this region back to the nGS. Through these identified connections
      several mechanisms for the processing of gustatory information can be proposed.
      The descending projections from the nLB and nLT could provide feedback to the
      primary and secondary gustatory nuclei, and could modulate feeding-related motor
      circuits in the medulla. The connections of nCLI and nLBp with the telencephalon
      allow for the involvement of gustation in learning processes and other complex
      behaviors.

PMID- 7506717
TI  - Treatment of postprandial hypotension with selective alpha 1 and beta 1
      adrenergic agonists.
AB  - In order to treat postprandial hypotension (PPH), we orally administered a
      combination of denopamine (10 mg, a selective beta 1-adrenergic agonist) and
      midodrine-HCl (4 mg, a selective alpha 1-adrenergic agonist) to eight patients
      with autonomic failure (AF) prior to and after eating. When the patients were
      given 75 g glucose with 225 ml water without drugs, blood pressure fell
      subsequently, cardiac output (CO) was unchanged, and vascular resistance of the
      lower legs (LVR) decreased. However, concomitant administration of denopamine and
      midodrine-HCl prevented PPH and increased CO and LVR. The portal blood flow was
      not indifferent to the drugs. A marked increase in heart rate after drug
      administration was seen in some patients with AF, which reflects the
      supersensitivity to denopamine. Combined oral administration of denopamine and
      midodrine-HCl is a safe and useful therapy for PPH in patients with AF.

PMID- 7506716
TI  - Direct projections from the anterior thalamic nuclei to the retrohippocampal
      region in the rat.
AB  - The present study examined the areal and laminar distribution of direct
      projections from the anterior thalamic nuclei to the retrohippocampal region in
      the rat, with anterograde transport of Phaseolus vulgaris-leucoagglutinin. The
      anteromedial nucleus (AM) projects to the temporal subiculum, medial entorhinal
      area, perirhinal area, and caudomedial part of the lateral entorhinal area. The
      interanteromedial nucleus (IAM) projects to the perirhinal area and the
      caudolateral part of the lateral entorhinal area. Furthermore, both the AM and
      IAM project to the temporal area 2, occipital area 1, and lateral occipital area
      2. The projections from the AM and IAM to these retrohippocampal and neocortical
      regions terminate mainly in deep layers. The anteroventral nucleus (AV) projects
      to the subicular complex with a complex topographic organization. The most
      rostral part of the AV projects to layers I and III of the ventral presubiculum,
      the pyramidal cell layer of the temporal subiculum, and deep layers of the
      parasubiculum and medial entorhinal area. At the midrostrocaudal level of the AV,
      the lateral and the dorsal quadrants of the AV project, respectively, to layers I
      and III and to layers I and IV-VI of the ventral presubiculum, whereas the
      ventral and the medial quadrants project, respectively, to layers I and III and
      to layers I and IV-VI of the dorsal presubiculum. Furthermore, the lateral and
      dorsal quadrants project to the pyramidal cell layer of the temporal subiculum,
      whereas the ventral and medial quadrants project more septally. At the caudal
      third level of the AV, the dorsolateral part projects to layers I and III of the
      presubiculum with a patchy pattern and to the pyramidal cell layer of the septal
      subiculum. The anterodorsal nucleus projects mainly to deep layers of the
      presubiculum, parasubiculum, and entorhinal area. The results show that each
      subdivision of the anterior thalamic nuclei projects to a distinct field in the
      retrohippocampal region. This suggests that each of these projections may have a
      distinct modulatory influence upon the activity of retrohippocampal neurons that
      play important roles in limbic functioning such as memory and learning processes.

PMID- 7506718
TI  - Histologic differentiation and motility of rat stomach.
AB  - An ultrastructural and immunohistochemical study was done to investigate the
      normal developmental process of rat gastric wall. Neuronal processes were
      observed on the external side of immature muscle cells on gestational day 15, and
      Auerbach's plexus was found on gestational day 18, after which neuronal elements
      extended just under the subepithelial area. Myofilaments appeared in
      undifferentiated mesenchyme cells on gestational day 15. On day 17, stomach was
      responsive to Ach stimulation. On the day after the initiation of gastric
      motility, gastric glands started to form on the mucosal surface. At the same
      developmental stage, some parts of the mucosal epithelium and the submucosal
      connective tissues were stained with antiserum against tenascin. Endocrine and
      parietal cells appeared in the mucosal epithelium on gestational day 19. Dense
      secretory granules on the apical surface of mucosal epithelium were increased
      between day 20 and 21. The cytoplasmic organelles gradually developed with
      advancing fetal age. We suggest that tenascin may play a role in gastric gland
      formation and that there are some relationships between gastric gland formation
      and gastric motility. We believe that the development of subepithelial tissues
      may be closely associated with epithelial growth.

PMID- 7506719
TI  - Medical metaphors in English moral theology, 1560-1660.

PMID- 7506720
TI  - Characterization and function of the NKR-P1dim/T cell receptor-alpha beta+ subset
      of rat T cells.
AB  - MHC-unrestricted cytotoxicity is mediated primarily by NK cells. However, some
      subsets of TCR-alpha beta+ and TCR-gamma delta+ T cells also have the capacity to
      mediate MHC-unrestricted cytotoxicity, particularly after incubation in high
      concentrations of IL-2. Currently, it is not known what receptors on T cells are
      responsible for this activity, nor whether such receptors are the same as those
      on NK cells. We have recently described a type II integral membrane protein,
      termed NKR-P1, that is expressed at high levels on rat NK cells (NKR-P1bright).
      NKR-P1 contains a carbohydrate recognition domain characteristic of C-type
      (Ca(2+)-dependent) animal lectins and is a representative member of a distinct
      group of this superfamily. By a variety of criteria, NKR-P1 is linked to a
      signaling pathway that activates NK cell lytic function. Based on its structure
      and function, NKR-P1 has been implicated as a candidate molecule involved in or
      contributing to MHC-unrestricted cytotoxicity. We describe herein the expression
      of NKR-P1 at low levels on a small subset of rat T cells with an NKR-P1dim/TCR
      alpha beta+ phenotype and on a small subset of cells with an NKR-P1dim/TCR-alpha
      beta- phenotype (presumably containing gamma delta+ T cells). Before incubation
      with IL-2, the NKR-P1dim subsets of cells lack MHC-unrestricted cytolytic
      capacity and lack the capacity for reverse antibody-dependent cellular
      cytotoxicity (rADCC) mediated via NKR-P1. However, culture of NKR-P1dim/TCR-alpha
      beta+ T cells in IL-2 led to the acquisition of both MHC-unrestricted
      cytotoxicity and the capacity for rADCC via NKR-P1. NK-like cytolytic function
      was not found among IL-2-activated NKR-P1-/TCR-alpha beta+ T cells. These data
      suggest that expression of functional NKR-P1 (i.e., ability to signal rADCC)
      correlates with and potentially contributes to MHC-unrestricted cytotoxicity.

PMID- 7506721
TI  - Expression of tenascin in thymus and thymic nonlymphoid cells.
AB  - Tenascin (TN) is an extracellular matrix glycoprotein that is widely expressed in
      fetal tissues and tumor matrices but is absent from most normal adult tissues. It
      is transiently expressed at sites of wound healing and has been shown to inhibit
      some types of T cell activation. We have examined the expression of TN in rat and
      human thymic tissue. Our results indicate that TN is expressed in both neonatal
      and adult rat thymus, and that in human thymus TN is present in a meshlike
      network at the corticomedullary junction. In addition, cultured human thymic non
      lymphoid cells grown in serum-containing medium synthesize TN, whereas under
      serum-free conditions these cells secrete TN in response to transforming growth
      factor-beta.

PMID- 7506722
TI  - Monocytes provide a novel costimulatory signal to T cells that is not mediated by
      the CD28/B7 interaction.
AB  - Resting CD4+T cells must receive nonspecific costimulatory signals from APC to
      produce maximal amounts of IL-2 in response to TCR signaling. The T cell-specific
      surface molecule CD28 is one protein that transduces a costimulatory signal
      following interaction with its ligand B7. We report here the identification of
      another contact-mediated costimulatory signal provided by the human histiocytic
      line U937 and by purified monocytes. Although this monocyte-derived costimulus is
      not transduced by the CD28/B7 interaction, it synergizes with the CD28 signal to
      elicit maximal IL-2 production from freshly isolated T cells. IL-2 production by
      previously activated CD8+ T cells depends on the monocyte-derived costimulatory
      signal, although memory CD4+ T cells respond well to either the monocyte-derived
      costimulus or B7-derived costimulation. In contrast, IL-2 secretion by naive T
      cells appears to require the synergistic interaction between both costimulatory
      pathways. These results suggest that the array of costimulatory ligands expressed
      by various APC affects the magnitude of the T cell response and also which T cell
      subsets are stimulated.

PMID- 7506723
TI  - Ligation of CD40 induces sterile transcripts of multiple Ig H chain isotypes in
      human B cells.
AB  - Stimulation of human B cells with mAb to CD40 in the presence of IL-4 induces
      proliferation and differentiation into Ig-secreting cells. To delineate the
      molecular events leading to Ig secretion after stimulation via the CD40 molecule,
      the induction of germ-line transcripts of Ig H chain isotypes was analyzed by
      polymerase chain reaction. The results document that costimulation with mAb to
      CD40 and IL-4 induces sterile transcription of all Ig H chain isotypes. Of
      importance, stimulation with mAb to CD40 without the addition of IL-4 induced
      germ-line transcription of most downstream isotypes, suggesting that this signal
      is sufficient to initiate the first step in switch recombination.

PMID- 7506724
TI  - Long term activation of natural killer cells results in modulation of beta 1
      integrin expression and function.
AB  - Integrin expression and function is largely modulated by cell activation. Here we
      provide evidence that long term activation of human NK cells results in a marked
      modulation of beta 1-integrin expression and adhesive functions. By flow
      cytometry and immunochemical analysis we have detected induction of alpha 1 beta
      1 and alpha 2 beta 1, increased expression of alpha 4 beta 1 and alpha 5 beta 1,
      and decline of alpha 6 beta 1 on CD3-CD56+ NK cells generated from 10-day
      coculture of nonadherent PBMC with irradiated RPMI 8866 EBV+ lymphoblastoid B
      cell line. Adhesion assays performed on extracellular matrix-coated plates showed
      that, unlike fresh NK cells, long term-activated NK cells bind to native collagen
      I via alpha 2 beta 1 and to heat-denatured collagen I in an RGD-dependent manner,
      although they lose the ability to bind to laminin. In regard to the adhesion to
      FN, no major quantitative changes are observed after long term NK cell
      activation. However, whereas alpha 4 beta 1 and alpha 5 beta 1 completely mediate
      the adhesion of fresh NK cells to fibronectin, binding of activated NK cells is
      only partially beta 1-dependent and seems to involve also non-beta 1-integrin(s)
      recognizing and RGD sequence. The modulation of beta 1-integrin expression and
      the acquisition of new adhesive properties on long term-activated NK cells may be
      relevant for their traffic and tissue localization during inflammation and immune
      response.

PMID- 7506725
TI  - Inducible binding of human lymphocytes to hyaluronate via CD44 does not require
      cytoskeleton association but does require new protein synthesis.
AB  - We have examined molecular mechanisms of the PMA-inducible HA binding ability of
      human lymphocytes. Newly established OS/6 and OS/37, specific for human CD44,
      specifically inhibited PMA-induced HA binding of several human cell lines,
      suggesting that both mAb detect HA binding epitope(s) on CD44. Sequential
      staining revealed that these mAb cross-blocked each other's binding to Molt-4, T
      lymphoblast lines, and that neither of them interfered with staining of Molt-4 by
      other anti-CD44 mAb which induced significant homotypic cell aggregation.
      Biochemical and PCR analyses did not provide any evidence that PMA stimulation
      induced dramatic changes in molecular weight or molecular isoforms of CD44.
      Interestingly, HA binding was not affected and rather slightly increased by
      cytochalasin B which disrupts F-actin microfilament integrity. This suggests that
      the ability of CD44 to bind to HA does not correlate with the association of CD44
      with the cytoskeleton. On the other hand, protein synthesis inhibitors,
      cycloheximide and anisomycin clearly inhibited the induction of HA binding of PMA
      activated Molt-4 without affecting the expression of CD44 at the same time after
      stimulation. The same treatment had no effect on PMA-induced FN binding of the
      cells, which was mediated by VLA integrins. These results suggest that the
      adhesion functions of CD44 and integrins are differently regulated despite the
      fact that both are induced by PMA stimulation, and that new protein synthesis is
      essential for the PMA-induced HA binding by CD44.

PMID- 7506726
TI  - Expression and function of CD7 molecule on human natural killer cells.
AB  - The CD7 molecule, one of the earliest T-lymphocyte Ag expressed during ontogeny,
      has recently been demonstrated to facilitate activation of T cells and to
      preferentially activate TCR-gamma/delta + subset of T cells. The CD7 Ag is also
      expressed on human NK cells, but its function has not been determined. In this
      study, expression and function of CD7 Ag on highly enriched NK cells (94 +/- 3%
      mean +/- SD, n = 12) obtained by negative selection from peripheral blood of
      normal donors were investigated. The CD7 Ag was found to be expressed at a
      significantly (p < 0.002) higher level on fresh NK cells than on IL-2-activated,
      NK cells. CD7 on human NK cells was found to be a signal-transducing molecule
      with a rapid increase in cytoplasmic free calcium observed on binding of anti-CD7
      mAb to the surface of NK cells. Cross-linking of CD7 induced expression of
      surface activation molecules such as CD25, CD71, HLA-DR, CD69, and CD54.
      Activation by anti-CD7 mAb cross-linked to plastic or through goat anti-mouse Ig
      also induced a variety of NK cell functions: it stimulated secretion of IFN
      gamma, led to proliferation of NK cells, as measured by [3H]thymidine
      incorporation, and significantly enhanced cytotoxicity of NK cells against K562
      targets (p < 0.03). However, CD7 on NK cells did not seem to transduce a lytic
      signal, because it neither mediated redirected killing of Fc gamma R+ murine
      mastocytoma P815 cells nor triggered lysis of a hybridoma expressing the antibody
      in a membrane-bound form. CD7 molecules appeared to have a regulatory role in
      adhesion of NK cells to fibronectin, because cross-linking of CD7 on resting NK
      cells significantly augmented their adhesion to fibronectin-coated plastic
      surfaces. However, this induced adhesion was not associated with increased
      expression of beta 1-integrins on NK cells. Thus, CD7-mediated signals appear to
      augment function of adhesion molecules on NK cells, which may be involved in NK
      cell activation by providing both anchorage and costimulatory triggering.

PMID- 7506727
TI  - CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B
      cell activating molecule/CD40-L. Potential role in regulating helper effector
      function.
AB  - The T-BAM/CD40-L molecule on CD4+ T cells interacts with B cell CD40 molecules to
      deliver contact-dependent signals that drive B cell activation and Ig secretion.
      Cell surface T-BAM/CD40-L expression is transient and may be closely regulated in
      order to limit the activation and clonal selection of noncognate B cells. We
      demonstrate that B cells, but not non-B cells, rapidly and specifically down
      modulate surface T-BAM/CD40-L expression in a contact-dependent and temperature
      sensitive manner that renders T cells unable to activate resting bystander B
      cells. Because the ability to down-modulate T-BAM/CD40-L correlated with CD40
      expression, the role of CD40 molecules in down-modulating its ligand was directly
      assessed. Anti-CD40 mAb, but not control mAb, block B cell-induced T-BAM/CD40-L
      down-modulation. Furthermore, CD40+ nonlymphoid transfectants specifically down
      modulate surface T-BAM/CD40-L expression. B cells induce T-BAM/CD40-L
      internalization into cytoplasmic compartments in a process that is inhibited by
      cytochalasin B. Pretreatment of activated T cells with lysosomotropic agents does
      not affect CD40-induced down-modulation of surface T-BAM/CD40-L but results in a
      marked accumulation of T-BAM/CD40-L in cytoplasmic vesicles. Together, these
      studies strongly suggest that CD40 induced T-BAM/CD40-L down-modulation occurs,
      in part, by receptor-mediated endocytosis followed by lysosomal degradation and
      may represent a mechanism to regulate CD4+ T cell helper effector functions.

PMID- 7506728
TI  - Endogenous peptides with distinct amino acid anchor residue motifs bind to HLA-A1
      and HLA-B8.
AB  - Distinct amino acid (aa) residue motifs for peptides binding to HLA-A1 and HLA-B8
      were identified by sequence analyses of reversed-phase HPLC fractions containing
      endogenous peptides derived from these HLA molecules. Fifteen different primary
      sequences were determined for HLA-A1-associated peptides, 12 of which were nine
      aa in length. Common features among these peptide sequences were Tyr at the COOH
      terminus, a negatively charged aa (usually Glu) at position 3 (P3), and Pro at
      P4. Twenty-seven different primary sequence assignments were made for HLA-B8
      associated peptides, most of which were eight aa in length. Lys, and in a few
      cases Arg, predominated at P3 and P5; Leu and Pro predominated at P2, and Leu was
      the preferred COOH-terminal residue. Unlike all other human class I molecules
      whose peptide-binding properties have been studied, both HLA-A1 and HLA-B8
      endogenous peptide sequences have a dominant anchor residue at P3, and these aa
      are opposite in charge to the aa at position 156 of the peptide-binding site.
      Synthetic peptides corresponding to endogenous peptide sequences bound to their
      respective HLA molecules in vitro, indicating that they derive from peptides
      bound to HLA and not from copurifying contaminants. Eight of the HLA-A1 and HLA
      B8 endogenous peptide sequences matched intracellularly expressed proteins found
      in protein sequence data bases. The HLA-A1 peptide-binding motif was then used to
      identify potential antigenic peptides from influenza A viral proteins that bound
      to HLA-A1 in vitro.

PMID- 7506729
TI  - Identification of a protein, SPY75, with repetitive helix-turn-helix motifs and
      an SH3 domain as a major substrate for protein tyrosine kinase(s) activated by Fc
      epsilon RI cross-linking.
AB  - Cross-linking of the high affinity receptor for IgE (Fc epsilon RI) initiates
      various biochemical and morphologic changes leading to degranulation and
      synthesis and release of cytokines and lipid mediators. Tyrosine phosphorylation
      of several cellular proteins was previously reported as the earliest signaling
      event for the Fc epsilon RI signal transduction pathway. By amino acid sequence
      determination and cDNA cloning analysis, a 75-kDa protein, termed SPY75, was
      identified as a major tyrosine-phosphorylated protein in activated mouse mast
      cells. SPY75, barely tyrosine phosphorylated in resting cells, was rapidly and
      transiently tyrosine phosphorylated on Fc epsilon RI cross-linking in an Ag
      concentration-dependent manner. Similar SPY75 tyrosine phosphorylation was
      observed when Ag receptors on B and T lymphocytes were cross-linked by
      appropriate antibodies. However, IL-3, granulocyte macrophage-CSF, or stem cell
      factor did not induce tyrosine phosphorylation of SPY75 in PT-18 mast cells,
      despite their responsiveness to these cytokines. SPY75 was not physically
      associated with the receptor or other known signaling molecules. This protein,
      the mouse homologue of the human HS1 gene product, has putative repetitive helix
      turn-helix motifs found in many DNA-binding proteins and a putative nuclear
      transport signal. It also has a Src homology 3 domain, which is found in many
      signaling molecules and cytoskeletal proteins. These structural features and the
      rapid tyrosine phosphorylation on Fc epsilon RI cross-linking suggest that the
      signal generated by Fc epsilon RI cross-linking is transmitted through tyrosine
      phosphorylation of SPY75.

PMID- 7506730
TI  - The fifth domain of beta 2-glycoprotein I contains a phospholipid binding site
      (Cys281-Cys288) and a region recognized by anticardiolipin antibodies.
AB  - We have identified a phospholipid binding site in the fifth domain of beta 2
      glycoprotein I (beta 2-GPI). Using synthetic peptides spanning the fifth domain
      of beta 2-GPI, we have shown that the presence of the sequence Glu274-Cys288
      caused a decrease in the binding of purified anticardiolipin (aCL) antibodies in
      a modified cardiolipin (CL)-ELISA by inhibiting the binding of beta 2-GPI to CL.
      This peptide bound to and could be eluted from a CL affinity column in a manner
      similar to native beta 2-GPI. Peptides corresponding to other regions of the
      fifth domain had no inhibitory effect. The inhibitory activity was restricted to
      the sequence Cys281-Lys-Asn-Lys-Glu-Lys-Lys-Cys288. Peptides in which the two
      flanking cysteine residues were deleted or substituted with serine residues
      possessed no inhibitory activity, indicating that the conformation of this highly
      positively charged sequence may be critical for phospholipid binding. aCL
      antibodies purified from patients with autoimmune disease were shown to bind
      directly to wells coated with native beta 2-GPI but not to wells coated with a
      preparation of beta 2-GPI cleaved between Lys317 and Thr318. The integrity of
      this sequence is therefore critical for these antibodies to recognize beta 2-GPI,
      and the putative epitope for aCL antibodies is most likely to be in this region.

PMID- 7506731
TI  - Characterization of DAF-2, a high molecular weight form of decay-accelerating
      factor (DAF; CD55), as a covalently cross-linked dimer of DAF-1.
AB  - Human E express two surface forms of decay-accelerating factor (DAF; CD55). On
      SDS-PAGE under reducing conditions the major form, DAF-1, migrates as a 70-kDa
      protein and the minor form, DAF-2, present at < 10% the amount of DAF-1, migrates
      as a 140-kDa protein (Kinoshita, T., S. I. Rosenfeld, and V. Nussenzweig. 1987.
      J. Immunol. 138:2994). Both forms possess decay-accelerating activity and, after
      purification from solubilized E, reinsert into sheep E, indicating a
      glycosylphosphatidylinositol anchor. In contrast to human cells, these two forms
      of DAF from orangutan E are expressed in approximately equal amounts (Nickells,
      M. W., and J. P. Atkinson. 1990. J. Immunol. 144:4262). An orangutan B lymphocyte
      cell line, CP81, also expresses similar quantities of both forms. These sources
      of orangutan DAF were utilized for further characterization of DAF-2. Orangutan
      and human DAF-1 were 98% and 95% homologous at the nucleotide and amino acid
      levels, respectively. Northern and Southern analyses of orangutan DAF were also
      similar to those for human DAF. Tryptic peptide maps of DAF-1 and DAF-2 were
      identical. After treatment with phosphatidylinositol-specific phospholipase C and
      glycosidases, the change in M(r) of DAF-2 was consistent with it possessing two
      glycosylphosphatidylinositol anchors and twice as much oligosaccharide as DAF-1.
      Biosynthetic analysis demonstrated a single 46-kDa precursor for both forms.
      Taken together, these data indicate that DAF-2 is a covalently cross-linked dimer
      of DAF-1. Analysis of a series of human DAF deletion mutants localized the cross
      link(s) within the short consensus repeat domains.

PMID- 7506732
TI  - Direct sequence identification and kinetic analysis of an MHC class I-restricted
      Listeria monocytogenes CTL epitope.
AB  - Murine infection with the intracellular bacterium Listeria monocytogenes elicits
      MHC class I-restricted CTL with specificity for multiple bacterial peptides. The
      variety and relative abundance of self-peptides bound by MHC molecules make
      identification of pathogen-derived peptides difficult. In this report, the
      sequence of a pathogen-derived CTL epitope is determined by direct analysis of
      peptides extracted from MHC class I molecules. The epitope, p60 217-225, is
      presented to L. monocytogenes-specific CTL by the H-2Kd MHC class I molecule and
      is derived from p60, a secreted invasion-associated protein. Quantitation of p60
      217-225 in infected cells shows that this epitope is detectable within 2 h of
      infection and, after a 9-h infection, there are over 3000 epitopes per infected
      cell. This contrasts with listeriolysin 91-99, the other major L. monocytogenes
      epitope, which is present in quantities below 200 epitopes per cell until 5 h of
      infection and reaches 800 epitopes per cell 9 h after infection. This report
      shows that identifying new T lymphocyte epitopes by direct sequence analysis of
      peptides isolated from MHC molecules is feasible. Furthermore, kinetic and
      quantitative analysis of T cell epitopes in infected cells is a useful approach
      to investigate the multispecific CTL response to complex intracellular pathogens.

PMID- 7506733
TI  - Structure-function analysis of human IFN-alpha. Mapping of a conformational
      epitope by homologue scanning.
AB  - The purpose of this study was to map a conformational epitope of a mAb that binds
      the IFN subtype alpha 4a. Binding of this mAb, designated I-4-A, to IFN-alpha 4a
      does not block receptor binding, but does neutralize biologic activity by
      inhibition of signal transduction. A novel strategy was developed, termed
      homologue scanning, which uses template-coupled polymerase chain reaction to
      generate hybrid molecules consisting of part (N-terminus) of the reactive IFN
      alpha 4a subtype to locate the epitope, and the remainder of the nonreactive IFN
      alpha 14 subtype to provide the overall conformation of an IFN-alpha molecule.
      Hybrid molecules were expressed as 35S-methionine-labeled proteins and tested for
      immunoreactivity by Western blotting and antiviral activity by cytopathic effect
      reduction bioassays. Unless an entire IFN-alpha (hybrid) molecule was formed,
      immunoreactivity and biologic activity were lost, indicating the importance of
      the C-terminus for correct folding of IFN-alpha molecules. The epitope for I-4-A
      was localized to the N-terminal 23 residues of IFN-alpha 4a. Furthermore, the
      immunoreactivity of IFN-alpha 4a analogues, with alterations in the putative
      receptor-binding region of IFN-alpha 4a residues 30 to 40 was unaffected, in
      contrast to the biologic activity that was reduced by several orders of
      magnitude. Thus, the N-terminal 23 residues of IFN-alpha 4a, which probably are
      not involved in receptor binding, may be important for other interactions of the
      receptor-bound ligand. In general terms, the novel approach of homologue
      scanning, using template-coupled PCR to facilitate the generation of hybrid
      proteins, will have broad application in the mapping of conformational epitopes
      of proteins that are members of a homologous family. The ability to identify
      conformational epitopes will increase our understanding important interactions of
      proteins with antibodies, receptors, and other macromolecules.

PMID- 7506734
TI  - Differences between human eosinophils and neutrophils in the function and
      expression of sialic acid-containing counterligands for E-selectin.
AB  - Both neutrophils and eosinophils have been shown to bind to the inducible
      endothelial cell adhesion molecule E-selectin. For neutrophils, one of the
      reported ligands for E-selectin is the sialylated Lewis X Ag (sLe(x)). To analyze
      the counterligands on eosinophils for E-selectin, adhesion assays were performed
      in which purified leukocytes were allowed to adhere to a soluble recombinant form
      of the molecule immobilized on plastic plates. Eosinophils, like neutrophils,
      bound to immobilized E-selectin, but significantly more neutrophils than
      eosinophils adhered in this assay. Consistent with the greater ability of
      neutrophils to bind E-selectin was the observation by flow cytometry that
      neutrophils expressed significant levels of sLe(x) and a sialylated dimeric form
      of the Le(x) Ag (sialyl-dimeric Le(x), or sialyl-stage-specific embryonic Ag-1,
      recognized by mAb FH6), whereas the expression of these epitopes on eosinophils
      was extremely low or undetectable. Expression was similar on eosinophils from
      allergic and nonallergic donors, and was not altered on eosinophils after
      induction of L-selectin shedding in vitro by treatment with platelet-activating
      factor. For both eosinophils and neutrophils, treatment with sialidase was
      associated with the complete elimination of sLe(x) and sialyl-dimeric Le(x)
      surface expression, and abolished leukocyte adhesion to E-selectin. Another
      glycosidase, endo-beta-galactosidase, which specifically cleaves the beta 1-4
      galactose linkage to N-acetyl-glucosamine when it exists in an extended chain
      form such as that found in sialyl-dimeric Le(x), significantly inhibited
      eosinophil and neutrophil adhesion and expression of sialyl-dimeric Le(x). Such
      treatment also reduced sLe(x) expression on eosinophils, while having little
      effect on total neutrophil sLe(x) expression. For both eosinophils and
      neutrophils the sialylated ligand did not appear to be a glycoprotein because
      pretreatment of leukocytes with several proteases had no effect on adhesion to E
      selectin or on expression of sLe(x) and sialyl-dimeric Le(x). These data suggest
      that eosinophils, like neutrophils, use sialylated, protease-resistant structures
      to bind to E-selectin, although the eosinophil expresses much lower levels of
      these structures on its surface. A major proportion of the sLe(x)-containing E
      selectin ligand on the surface of eosinophils appears to be in the form of sialyl
      dimeric Le(x), whereas this represents a minor proportion on the surface of
      neutrophils. Based on results using endo-beta-galactosidase, it appears that
      these cells may rely disproportionately upon the cell surface sialyl-dimeric
      Le(x) to bind to E-selectin.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7506735
TI  - Substance P enhances the secretion of tumor necrosis factor-alpha from neuroglial
      cells stimulated with lipopolysaccharide.
AB  - The neuropeptide, substance P (SP), can stimulate secretion of TNF-alpha from
      macrophages. Neuroglia have SP receptors and subserve various macrophage-like
      functions in the central nervous system. We investigated whether SP stimulates
      secretion of TNF-alpha from primary cultures of neuroglial cells containing both
      astrocytes (approximately 90%) and microglia (approximately 10%). SP alone had no
      effect; however in the presence of LPS (10 ng/ml), SP (1 to 10 nM) caused a dose
      dependent increase in TNF-alpha secretion above the level measured in response to
      LPS alone. The effective doses of SP correlated with 125I-labeled Bolton Hunter
      conjugated SP binding (Kd 0.2 nM) to these cultures. Incubation with LPS did not
      change the number or affinity of SP-binding sites. In cultures enriched for
      microglia (> 99% pure), LPS stimulated the secretion of TNF-alpha but SP caused
      no enhancement. Microglia have no detectable 125I-labeled Bolton-Hunter
      conjugated SP binding sites in the presence or absence of LPS. These results
      indicate that the action of SP is mediated through astrocytes. We investigated
      whether IL-1 mediates the SP enhancement of TNF-alpha secretion. Addition of IL-1
      neutralizing antisera to mixed cultures stimulated with both LPS and 10 nM SP
      decreased TNF-alpha secretion to the level observed with LPS alone. LPS alone
      stimulated the secretion of IL-1 in a dose-dependent manner in the primary
      cultures, and this LPS-mediated IL-1 secretion was enhanced by SP. This
      enhancement was not observed in microglial cultures. SP may therefore play a role
      in neuropathologies in which these cytokines have been implicated.

PMID- 7506737
TI  - Requirements for L-selectin in neutrophil-mediated lung injury in rats.
AB  - L-selectin requirements in three models of acute lung injury in rats have been
      identified: systemic activation of complement after intravenous infusion of cobra
      venom factor (CVF) and intrapulmonary deposition of IgG or IgA immune complexes.
      In the CVF model of lung injury, treatment of rats with hamster monoclonal IgG
      anti-rat-L-selectin (HRL-1) induced significant neutropenia, necessitating the
      use of F(ab')2 fragments, which did not cause neutropenia. Treatment of rats with
      F(ab')2 anti-L-selectin (HRL-1) resulted in significant reductions in lung
      permeability and hemorrhage in the CVF model. Morphologically, this treatment
      abrogated adhesive interactions of neutrophils with the pulmonary vascular
      endothelium. In the IgG immune complex model of injury, the parameters of injury
      were significantly reduced as a result of treatment with HRL-1. In both models
      protection was associated with reductions in lung myeloperoxidase content.
      Treatment of rats with a F(ab')2 form of hamster monoclonal IgG non-blocking anti
      L-rat selectin, HRL-2, failed to show protective effects in the CVF and IgG
      immune complex models of lung injury. In the IgA immune complex model of injury,
      which is neutrophil-independent and related to toxic products from pulmonary
      macrophages, no protective effects of anti-L-selectin (HRL-1) were found.
      Therefore, in neutrophil-dependent and oxygen radical mediated lung injury, L
      selectin plays a requisite role in tissue recruitment of neutrophils. In the
      neutrophil-independent model of lung injury, no requirement for L-selectin
      appears to exist.

PMID- 7506736
TI  - Taxol provides a second signal for murine macrophage tumoricidal activity.
AB  - The anticancer drug, taxol, blocks cell division by stabilizing microtubules.
      However, taxol has distinct cell-cycle-independent effects. For example, taxol
      and bacterial LPS induce strikingly similar responses in murine macrophages. Here
      we report that taxol, like LPS, provides a "second" signal for murine macrophage
      activation to tumoricidal activity. Tumoricidal activity was determined by the
      release of 51Cr from prelabeled P815 mastocytoma target cells. Taxol or LPS alone
      weakly induced C3H/OuJ (Lpsn) murine macrophages to kill P815 mastocytoma cells,
      and tumoricidal activity was not induced by the classic "priming" signal, IFN
      gamma. However, combinations of taxol or LPS with IFN-gamma synergized to
      activate macrophages to lyse tumor cells. Taxol activation of macrophages
      required an intact LPS signaling pathway, as taxol did not induce IFN-gamma
      treated C3H/HeJ (Lpsd) macrophages to lyse target cells. In normal (Lpsn) murine
      macrophages, IFN-gamma, LPS, or taxol alone induced low or moderate levels of
      nitric oxide synthase gene expression and nitric oxide secretion. However, this
      gene and cytostatic metabolite were induced synergistically by combinations of
      taxol or LPS with IFN-gamma. Secretion of nitric oxide correlated with tumor cell
      killing, and taxol-activated macrophages failed to kill tumor targets in the
      presence of NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide
      synthase. The data illustrate the potential for taxol to activate macrophage
      mediated-antitumor mechanisms in addition to its better characterized role as an
      anti-mitotic agent.

PMID- 7506738
TI  - Signal transduction pathways mediating astrocyte IL-6 induction by IL-1 beta and
      tumor necrosis factor-alpha.
AB  - One immune function of astrocytes is IL-6 production. Synthesis of IL-6 within
      the central nervous system (CNS) can produce several different responses, acting
      on glia, neurons, and lymphocytes infiltrating brain tissue, and some of these
      effects are associated with CNS autoimmune disease. IL-6 gene expression in
      astrocytes is regulated by cytokines, infectious agents, neuropeptides, and
      neurotransmitters, and most of these stimuli interact synergistically. To examine
      the integration of these diverse factors in the control of IL-6 production, we
      have studied the involvement of underlying signal transduction processes using
      neonatal rat astrocytes. We have focused on signal transduction related to the
      stimulation of IL-6 gene expression by IL-1 beta and TNF-alpha. Our results
      indicate that stimuli related to protein kinase C (PKC), such as PMA and calcium
      ionophore A23187, increase IL-6 expression, whereas pharmacologic inhibitors of
      PKC inhibit IL-6 induction by IL-1 beta and TNF-alpha. Furthermore, both IL-1
      beta and TNF-alpha stimulate PKC activity in astrocytes. Stimulators of the cAMP
      pathway, such as cholera toxin, forskolin, and dibutyryl cAMP, also induced
      astrocyte IL-6 gene expression. However, inhibition of the cAMP pathway effector,
      protein kinase A, did not reduce the induction of astrocyte IL-6 gene expression
      in response to IL-1 beta or TNF-alpha, and an ELISA for cAMP detected only very
      small increases in cAMP synthesis in response to these cytokines. These data
      suggest that although cAMP does activate astrocyte IL-6 gene expression, it is
      the PKC pathway that plays a primary role in the stimulation of astrocyte IL-6
      gene expression by IL-1 beta and TNF-alpha.

PMID- 7506739
TI  - Modulation of thrombospondin receptor expression during HL-60 cell
      differentiation.
AB  - Thrombospondin (TSP), a multifunctional homotrimeric glycoprotein of
      approximately 450,000 M(r), is a component of the extracellular matrix that
      mediates the adhesive interactions of several different cell types including
      hematopoietic progenitor cells. We have used the promyelocytic leukemia HL-60
      cell line to examine TSP receptor expression during differentiation of leukocytes
      along either the monocyte/macrophage or the polymorphonuclear leukocyte (PMN)
      pathway. 125I-labeled TSP binding to undifferentiated or differentiated HL-60
      cells was time-dependent reaching saturation by 45 min. Undifferentiated HL-60
      cells expressed a single class of heparin-inhibitable TSP receptors. Treating HL
      60 cells with PMA induced their differentiation to macrophage-like cells and
      resulted in a concomitant 10-fold increase in TSP receptor expression. As with
      undifferentiated cells, a single class of heparin-inhibitable receptors was
      observed. Treating HL-60 cells with DMSO induced their differentiation to PMN
      like cells and resulted in a fivefold increase in TSP receptor expression.
      However, in this case two classes of binding sites were apparent on PMN-like
      cells, only 40% of which were heparin inhibitable. This is reminiscent of TSP
      binding to normal peripheral blood PMN (S.J. Suchard, L.A. Boxer, and V.M. Dixit.
      1991. J. Immunol. 147:651). In parallel studies, we also examined TSP synthesis
      during HL-60 cell differentiation. Undifferentiated HL-60 cells synthesized and
      secreted TSP as assessed by immunoprecipitation. TSP synthesis increased about
      fourfold when cells were differentiated toward PMN-like cells. In contrast, TSP
      was not detected in macrophage-like cells. RNase protection assays showed that
      TSP transcript levels paralleled TSP protein expression during differentiation.
      These findings suggest that expression of both TSP and TSP receptors are
      differentially regulated during blood cell maturation.

PMID- 7506740
TI  - Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus
      induced demyelinating disease. VI. Potentiation of demyelination with and
      characterization of an immunopathologic CD4+ T cell line specific for an
      immunodominant VP2 epitope.
AB  - Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is
      a relevant mouse model of multiple sclerosis. Demyelination is linked to
      persistent TMEV infection of the central nervous system and characterized by
      perivascular inflammatory mononuclear infiltrates and primary demyelination. Our
      previous results have shown that susceptibility correlates with the temporal
      development of chronic virus-specific delayed-type hypersensitivity (DTH)
      responses and suggest that inflammatory processes mediated by T cells specific
      for an immunodominant determinant on virus capsid protein 2 (VP2(74-86)) play a
      major immunopathologic role in SJL/J mice. In this study we have further defined
      the T cell-dependent nature and specificity of the demyelinating process in
      susceptible SJL/J mice by showing that thymectomized irradiated bone marrow
      restored mice fail to develop chronic demyelination and that i.v. adoptive
      transfer of polyclonal TMEV-specific T cells before intracerebral infection with
      a suboptimal dose of the BeAn strain of TMEV led to increased incidence and
      accelerated onset of clinical disease. The data also show that demyelination is
      dependent on the activity of virus-specific CD4+ T cells because in vivo
      depletion with anti-CD4, but not anti-CD8, mAb led to significantly diminished
      incidence and severity of demyelination concomitant with a decrease in TMEV
      specific DTH reactivity. In addition, the adoptive transfer of a TMEV-specific,
      DTH-mediating CD4+ I-A(s)-restricted Th1 line (sTV1) specific for the
      immunodominant VP2(74-86) epitope also led to increased incidence and accelerated
      onset of clinical disease only in TMEV-infected recipients. Collectively, the
      results of this and the companion paper demonstrate the highly significant
      immunopathologic contribution of CD4+ T cell responses specific for an
      immunodominant viral epitope to the chronic central nervous system demyelination
      observed in TMEV-infected SJL/J mice.

PMID- 7506741
TI  - Identification of autoantibody epitopes of glutamic acid decarboxylase in stiff
      man syndrome patients.
AB  - Stiff-man syndrome is a neurologic disorder characterized by progressive rigidity
      of skeletal muscles. Deficiency of the neurotransmitter gamma-aminobutyric acid
      and autoantibodies to glutamic acid decarboxylase (GAD), the enzyme synthesizing
      gamma-aminobutyric acid, are closely associated with the disorder, although the
      relevant antigenic epitopes have not been identified. In the present study, sera
      from two patients with SMS was used in an immunoblotting assay with recombinant
      GAD67 (M(r) 67,000) and GAD65 (M(r) 65,000) isoforms to test whether SMS sera can
      recognize specific epitopes. We found that both SMS sera recognized the GAD65,
      but not the GAD67, isoform. Using 13 different synthetic GAD peptides to block
      the autoantibodies, two GAD65 epitopes were identified. One epitope recognized by
      both patients' sera, was blocked by the peptide representing amino acid residues
      354-368. In one patient only, blocking was also observed by a peptide
      representing residues 390-402, which includes the binding site of the GAD
      cofactor, pyridoxal 5'-phosphate. A single amino acid substitution in GAD65 at
      position 401 (leucine to proline) and representing the analogous GAD67 sequence
      in this region significantly reduced the peptide's inhibitory effect. These
      findings suggest that SMS GAD autoantibodies share distinct GAD65 linear epitopes
      and that some SMS patients' autoantibodies may block the active site, explaining
      SMS GABA deficiency.

PMID- 7506742
TI  - Gabexate mesilate vs aprotinin in human acute pancreatitis (GA.ME.P.A.). A
      prospective, randomized, double-blind multicenter study.
AB  - The authors report the results of a randomized, double-blind multicenter clinical
      trial on the use of gabexate mesilate vs aprotinin in the therapy of acute
      pancreatitis. The size of the study sample and the end points chosen for
      evaluation of the early systemic complications of the pancreatitis--carefully
      selected targets for reliable assessment of the efficacy of any protease
      inhibitor--lead to the conclusion that gabexate mesilate is more efficacious than
      aprotinin in reducing the early complications of necrotizing acute pancreatitis,
      if administered within 72 h of onset of symptoms. Its good tolerability means
      that it can be used safely even at the dose of 3 g/24 h.

PMID- 7506743
TI  - Cathepsin B inhibition in two models of acute pancreatitis.
AB  - The possible role of cathepsin B in the pathogenesis of two forms of acute
      pancreatitis was studied using the cathepsin B inhibitor known as E-64. In an
      edematous, nonfatal pancreatitis induced by supramaximal doses of cerulein,
      increases in the serum amylase and lipase levels were less pronounced in rats
      pretreated with E-64. Other parameters of pancreatic injury were unaffected by
      inhibition of cathepsin B. In a necrohemorrhagic type of pancreatic injury
      induced by retrograde infusion of bile salts into the pancreatic duct, E-64
      partially attenuated increases in serum levels of amylase and lipase, and in
      addition, reduced the activation of trypsinogen. However, the high mortality in
      this model of pancreatitis was not modified.

PMID- 7506744
TI  - Characterization of a new diphenylpyrazolidinone cholecystokinin antagonist in
      vitro isolated rat pancreatic acini.
AB  - The effects of a newly developed diphenylpyrazolidinone cholecystokinin (CCK)
      antagonist LY219,057 were examined in the isolated rat pancreatic acini and
      compared with those of devazepide (previously designated L364,718 or MK-329).
      LY219,057 caused a concentration-dependent inhibition of 100 pM CCK octapeptide
      (CCK-8)-stimulated amylase release, with a half-maximal inhibition (ID50) at
      287.5 +/- 28.4 nM and was 200 times less potent than devazepide (ID50 = 1.4 +/-
      0.2 nM). The antagonism was competitive in nature because LY219,057 caused a
      parallel rightward shift of the dose-response curve for CCK-8-stimulated amylase
      secretion without altering the maximal increase. LY219,057 significantly
      inhibited amylase release in response to CCK-8 and cerulein but had no effect on
      amylase release stimulated by other receptor secretagogs or agent bypassing
      receptors. LY219,057, whether added at the beginning or 20 min after the CCK-8
      stimulation, inhibited amylase release. This compound caused a residual
      inhibition of the action of CCK-8. Acini preincubated with 1.0 microM LY219,057
      for 30 min at 37 degrees C were threefold less sensitive to CCK-8 than the acini
      preincubated without LY219,057. These results indicate that LY219,057 acts as a
      potent, competitive, and specific CCK receptor antagonist of the action of CCK on
      the exocrine pancreas.

PMID- 7506745
TI  - Increased expression of a novel leukocytic factor in patients with hemolytic
      anemia.
AB  - Misprimed polymerase chain reaction (PCR) products were generated from the crude
      leukocytic DNA extract of four of five patients with hereditary hemolytic anemia,
      during the course of exon 6 pyruvate kinase L gene amplification. These by
      products, which originated from abundant mRNA templates, were not observed in
      seven healthy individuals. Two markers were cloned (GenBank accession numbers
      M64700 and M64701). We focused further studies on one of the human markers
      associated with hereditary hemolytic anemia, human DNA marker B (HUMDNAMB).
      HUMDNAMB is a 451-bp open reading frame that has never been described previously.
      The nucleic acid sequence region 303-416 is 63% homologous to a coding region of
      the bovine interferon alpha-A gene. Matrix analysis of the amino acid sequences
      reveals a structural similarity between the two proteins. The HUMDNAMB protein is
      expected to be larger than interferons, based on the size of its 2-kb messenger
      RNA detected by Northern blot in human leukocytes, fetal liver, and fetal
      intestine.

PMID- 7506746
TI  - Graded changes in the response of individual human basophils to stimulation:
      distributional behavior of early activation events.
AB  - These studies examine the distribution of single-cell responses in basophil
      preparations in the context of four events that may be associated with early
      activation by anti-immunoglobulin E (IgE) antibody and the bacterial peptide fMet
      Leu-Phe (fMLP). In general, we measured the single-cell response distributions
      after challenge with a concentration of stimulus that resulted in an optimal
      response and compared this with the distribution that occurred after challenge
      with suboptimal concentrations of the same stimulus. The elevation in cytosolic
      calcium, as detected in Fura-2-labeled basophils, after challenge with anti-IgE
      or fMLP showed graded characteristics in that the distributions were unimodal
      under conditions of optimal or suboptimal challenge with little skewing from a
      normal distribution. Similarly, the up-regulation of the cell surface adhesion
      molecule CD11b, as determined by flow cytometry, showed graded unimodal increases
      after challenge with anti-IgE antibody at optimal and suboptimal concentrations.
      In addition, stimulation of basophils led to increased F-actin polymerization.
      After challenge with an optimal concentration of anti-IgE antibody, the F-actin
      content of basophils increased to a maximum between 10 and 15 min and returned to
      near prechallenge levels by 60 min. There was a close correlation between the
      maximum increase in F-actin content and histamine release regardless of the
      stimulus; anti-IgE antibody, fMLP, and phorbol ester (PMA) responses lay on the
      same regression line. The single-cell F-actin polymerization distributions were
      also unimodal and graded according to the magnitude of the histamine release
      response. During measurements of the calcium response under the microscope we
      noted that basophils underwent significant changes in morphology after challenge
      with any stimulus. These changes were related to both degranulation and
      nondegranulation events and could be quantitated by a series of image-processing
      algorithms, which are presented. The kinetics of the morphological change,
      measured as a change in cell perimeter, paralleled degranulation. Single-cell
      distributions of the morphologic changes were also unimodal under conditions of
      both optimal and suboptimal stimulation. Therefore, no evidence of all-or-nothing
      responses could be observed in the context of these four early activation events.
      In general, the response distributions resembled normal distributions at both
      optimal and suboptimal levels of stimulation, which indicated that single
      basophils responded in a graded manner.

PMID- 7506747
TI  - Function and regulation of leukocyte homing receptors.
AB  - In vivo studies in the mid-1960s showed that lymphocytes home to various lymphoid
      compartments of the body in a tissue-specific manner. A central event in this
      process is adhesion of the leukocyte in the blood to specialized endothelial
      cells within the lymphoid organs. Leukocyte binding to the vascular endothelial
      cells involves many diverse adhesion molecules expressed by both cell types.
      Those adhesion molecules which contribute to the tissue specificity of the
      leukocyte-endothelial cell interactions are called "homing receptors." The study
      of homing receptors has progressed tremendously in recent years. The intent of
      this treatise is to review our current understanding of these molecules in the
      context of the lymphocyte and outline studies showing that these molecules have
      important functions for other leukocytes as well. A general overview of leukocyte
      endothelial cell adhesion will not be given: the reader can easily find many
      excellent and up-to-date reviews of this subject in the literature. This review
      is an attempt to outline the major contributions to the identification and
      characterization of homing receptors. Apologies are extended for any oversights
      made.

PMID- 7506749
TI  - Fiber pathways and positional changes in efferent perikarya of 2.5- to 7-day
      chick embryos as revealed with DiI and dextran amines.
AB  - The differentiation of facial motoneurons and inner ear (octaval) efferents was
      examined in chicken embryos by applying DiI or dextran amines to the cut VII/VIII
      nerve (peripheral label) or to the basal/floor plate of rhombomeres 4/5 (central
      label). Central labeling found axons of these efferent neurons to leave the brain
      as early as 2.5 days of incubation. Peripheral labeling identified cell bodies
      ipsilaterally in rhombomeres 4 and 5 at 2.5 days. Central labeling at 3.5 days
      showed these fibers to have fully segregated into separate pathways to the facial
      nerve and the inner ear and that the octaval efferent axons had reached the
      otocyst wall. By 3.5 days many peripherally labeled octaval efferent somata were
      found in the floor plate and by 5 days they were found bilaterally. At 6 days,
      selective peripheral labeling of either the VIIth or VIIIth nerve showed that the
      contralateral population consisted of octaval efferents and central label applied
      to the floor plate of rhombomeres 4/5 identified fibers that entered the octaval
      nerve via the facial root and entered the vestibular sensory epithelia. Together
      these data suggest an initial mingling of two different motoneuron populations
      (facial and octaval) in rhombomeres 4/5 and a subsequent segregation by
      differential migration. Our data also find a much earlier arrival of octaval
      efferent axons at the otic vesicle than previously described and suggest a
      contralateral migration of many octaval efferents beginning shortly after their
      axons reach the facial nerve root.

PMID- 7506748
TI  - Restoration of postburn impaired lymphocyte responsiveness by nonsteroidal anti
      inflammatory drugs is independent of prostaglandin E2 inhibition.
AB  - Prostaglandin E2 (PGE2) has been implicated in postburn immunosuppression, which
      is responsible for septic complications. In the present work, seven non-steroidal
      anti-inflammatory drugs (NSAIDs), differing by their capacity to inhibit the
      cyclooxygenase pathway, were compared for their ability to restore T lymphocyte
      proliferative responses evaluated 4 days after thermal injury in rats. Salicylic
      acid, 5-aminosalicylic acid, and niflumic acid, given daily, fully restored
      spleen cell responses to concanavalin A (Con A) and phytohemagglutinin. These
      drugs were active only at doses that were below the anti-inflammatory doses and
      did not modify normal spleen cell responses. In these conditions, indomethacin
      slightly restored lymphocyte reactivity, whereas acetylsalicylic acid,
      ketoprofen, and piroxicam were ineffective. PGE2 production by Con A-stimulated
      spleen cells from untreated burned rats and after treatment with niflumic acid or
      5-aminosalicylic acid did not correlate with the intensity of the proliferative
      response. Indomethacin, niflumic acid, and 5-aminosalicylic acid were added in
      vitro to spleen cells from normal and burned rats, at concentrations from 10(-7)
      to 10(-4) M. PGE2 production was strongly depressed by indomethacin and niflumic
      acid and not modified by 5-aminosalicylic acid. The proliferative response of
      normal spleen cells was depressed in a concentration-dependent manner by niflumic
      acid and slightly inhibited at the highest concentrations of indomethacin. In
      contrast, indomethacin concentration dependently restored the burn-impaired
      proliferative response, whereas niflumic acid further depressed it and 5
      aminosalicylic acid had no effect. These results demonstrate that only some
      NSAIDs are able to restore T lymphocyte reactivity impaired after thermal injury
      and that this property is not related to inhibition of PGE2 production.

PMID- 7506750
TI  - Distinct mode of microtubule-associated protein 2 expression in the
      neuroblastoma/glioma cell line 108CC15/NG108-15.
AB  - The properties of microtubule-associated protein-2 (MAP-2) expression were
      examined in a transformed cell line, and compared to neurons from rodent brain
      where evidence supports both transcriptional and nontranscriptional regulation of
      MAP-2 synthesis. A monoclonal antibody that recognizes a common epitope in the
      adult (HMW MAP-2) and juvenile (MAP-2c) forms was used in an immunoblotting assay
      to assess the protein levels in actively dividing and differentiated
      neuroblastoma/glioma (108CC15, also designated NG108-15) cells. Multiply
      phosphorylated MAP-2c was the predominant form in actively dividing cells,
      whereas HMW MAP-2 predominated in differentiated cells, which exhibited several
      other neuronal-like properties. A progressive increase in the levels of
      immunoreactive HMW MAP-2 was observed with increasing days of cell
      differentiation using dBcAMP as the inducing agent. However, the absolute levels
      of both HMW MAP-2 and MAP-2c in NG108-15 cells were significantly lower (at least
      10-fold) than levels measured in rodent brain. To assess whether there are
      correspondingly lower levels of HMW MAP-2 and MAP-2c mRNAs in NG108-15 cells,
      relative to rodent brain, a highly sensitive RNA amplification assay (reverse
      transcription-polymerase chain reaction; RT-PCR) was developed. Oligonucleotide
      primers were designed to specify either HMW MAP-2 mRNA or MAP-2c mRNA, and whole
      tissue RNA extracted from adult and neonatal rodent brain was used to verify the
      reliability of the RT-PCR assay. Accordingly, PCR products of the predicted size,
      specificity, and abundance were obtained, with similar levels of HMW MAP-2 mRNA
      and proportionately higher levels of MAP-2c mRNA in neonatal brain, relative to
      adult brain. MAP-2c mRNA was the predominant transcript in actively dividing
      NG108-15 cells, and the amount of HMW MAP-2 mRNA gradually increased and became
      the predominant transcript in cells exposed to dBcAMP for 6-9 days. Thus, the
      observed changes in MAP-2-specific mRNAs during differentiation paralleled
      changes in expressed protein, suggesting that MAP-2 synthesis in NG108-15 cells
      is transcriptionally controlled. However, the levels of both MAP-2 mRNAs in NG108
      15 cells were comparable to levels in rodent brain, despite the fact that MAP-2
      protein levels are at least 10-fold lower in NG108-15 cells. These data suggest
      that the low levels of HMW MAP-2 and MAP-2c protein expression in NG108-15 cells
      are not due to correspondingly lower levels of MAP-2 mRNAs, and that transformed
      neuronal cell lines demonstrate a unique mode of MAP-2 regulation.

PMID- 7506751
TI  - Therapeutic drugs in early pregnancy and congenital defects.
AB  - In a study of occupation and pregnancy outcome, information was collected on
      certain non-occupational factors including therapeutic drugs taken in the first
      trimester, reported by some 17% of women. A case-referent analysis was made of
      data from pregnancies leading to 787 major (class 1) and 2386 miscellaneous minor
      (class 2) congenital defects compared with pregnancies without defects, matched
      for hospital, maternal age and educational level. In pairs discordant for one of
      seven drug groups, ratios of positive pairs (case with drug) to negative pairs
      (referent with drug) were for class 1 defects 164:148, relative risk (RR) 1.11
      and for class 2 defects 433:383, RR 1.13. Only anti-infective drugs showed an
      increased RR: 1.70 (p = 0.06). This was mainly with nervous/sensory defects
      (10:2; RR 5.0, p = 0.04) but no one type of defect or type of drug was
      identified; the infections for which the drugs were given might have been
      responsible. For class 1 defects two pairs were positive for anti-convulsant
      drugs and two negative; no increase in risk was found for any specific drugs
      including doxylamine succinate (Bendectin).

PMID- 7506752
TI  - Membrane currents evoked by excitatory amino acid agonists in ON bipolar cells of
      the mudpuppy retina.
AB  - 1. Whole-cell patch-clamp recordings were obtained from ON bipolar cells in a
      retinal slice preparation of the mudpuppy, Necturus maculosus. The effects of
      excitatory amino acid (EAA) agonists applied in the presence of cobalt (2-5 mM)
      were examined. 2. At the holding potential of -50 mV, L-2-amino-4
      phosphonobutanoic acid (L-AP4, 5-10 microM) evoked an outward current accompanied
      by a conductance decrease. The zero current potential of the L-AP4-evoked current
      was near 0 mV independent of whether the intracellular Ringer solution contained
      CsCl or CsCH3SO4. The currents evoked by light were also accompanied by a
      conductance decrease and reversed near 0 mV. Replacing external sodium with
      choline or N-methyl-D-glucamine generated an outward current and suppressed the
      response to L-AP4. The response to L-AP4 was enhanced by removing extracellular
      calcium and suppressed by increasing extracellular calcium. These results
      indicate that L-AP4 closes nonspecific cation channels that are blocked by
      extracellular calcium. 3. In 2 mM cobalt, alpha-amino-3-hydroxy-5-methylisoxazole
      4-propionic acid (AMPA, 50-100 microM) evoked membrane currents that were
      accompanied by a conductance increase. AMPA-evoked currents exhibited a
      significant chloride dependence and were suppressed by gamma-aminobutyric acid-A
      (GABAA) antagonists bicuculline and picrotoxin; a GABA uptake blocker, nipecotic
      acid; and a glycine antagonist, strychnine. AMPA-induced currents were virtually
      absent in the presence of 5 mM cobalt and nominally 0 mM extracellular calcium.
      These results indicate that the conductance increase induced by AMPA in the
      presence of 2 mM cobalt is largely the result of calcium-dependent synaptic
      inputs onto GABAA and glycine receptors of ON bipolar cells. 4. N-methyl-D
      aspartic acid (250 microM) was ineffective when applied in the presence of 100
      microM cadmium or 2 mM cobalt. 5. 1S,3R/1R,3S-1-aminocyclopentane-1,3
      dicarboxylic acid (100-200 microM) evoked an outward current accompanied by a
      conductance decrease and appears to be an agonist at the L-AP4 receptor. 6. The
      findings of this study suggest that the only type of EAA receptor in mudpuppy ON
      bipolar cells is the L-AP4 receptor and that L-AP4 receptor activation results in
      the closing of nonspecific cation channels that are blocked by extracellular
      calcium.

PMID- 7506753
TI  - Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic
      currents in cultured rat hippocampal neurons.
AB  - 1. The effects of the volatile anesthetics enflurane, halothane, and isoflurane
      on gamma-aminobutyric acid (GABA) receptor-mediated inhibitory postsynaptic
      currents (IPSCs) were studied in cultured rat hippocampal neurons. The
      experimental concentrations of anesthetics were measured directly using gas
      chromatography. All three anesthetics increased the overall duration of IPSCs,
      measured as the time to half-decay (T1/2). Clinically effective concentrations of
      anesthetics [between 0.5 and 1.5 times MAC (minimum alveolar concentration)]
      produced between 100 and 400% increases in T1/2. These effects were fully
      reversible, and did not involve alterations in the reversal potential for the
      IPSC (EIPSC). 2. The decay of the IPSC was fitted as a sum of two exponential
      functions, yielding a fast component (tau fast = 20 ms), and a slow component
      (tau slow = 77 ms), such that the fast component accounted for 79% of the IPSC
      amplitude and 52% of the total charge transfer. All three anesthetics produced
      concentration-related increases in the amplitude and charge transfer of the slow
      component, while simultaneously decreasing the amplitude and charge transfer of
      the fast component. Thus T1/2 approximated tau fast under control conditions, but
      approximated tau slow in the presence of the anesthetics. 3. Varying the calcium
      chelating agents in the recording pipettes had no effect on the quality or
      magnitude of alterations in IPSC kinetics produced by halothane, suggesting that
      variations in intracellular calcium levels are not required for the effect of
      halothane on the time course of the IPSC. 4. The (+)-stereoisomer of isoflurane
      produced greater increases in the duration of the IPSC than the (-)-isomer when
      applied at approximately equal concentrations, suggesting that there is a
      structurally selective site of interaction for isoflurane that modulates the
      GABAA receptor. 5. These results suggest that the previously shown abilities of
      volatile anesthetics to potentiate responses to exogenously applied GABA and to
      prolong the duration of GABA-mediated synaptic inhibition may be due to an
      alteration in the gating kinetics of the GABAA receptor/channel complex.
      Prolongation of synaptic inhibition in the CNS is consistent with the
      physiological effects that accompany anesthesia and may contribute to the
      mechanism of anesthetic action.

PMID- 7506754
TI  - L-type calcium channels in type I cells of the rat carotid body.
AB  - 1. Whole-cell and cell-attached patch-clamp recordings were made from
      enzymatically isolated type I cells from the carotid body of adult rats. Voltage
      dependent K+ and Ca2+ channels were observed, but there was no detectable Na+
      current. In this respect, rat carotid body cells are unlike those from rabbit,
      which have Na+ currents and Na(+)-dependent action potentials. 2. The observed
      Ca2+ channels had the following properties: 1) activation requires voltage steps
      above -20 mV; 2) little inactivation occurred with holding voltages below -40 mV;
      3) one single-channel conductance of 21 pS was found with 90 or 110 mM Ba2+ in
      the cell-attached pipette and this was the only conductance observed; 4) open
      probability was increased by the dihydropyridine Ca2+ channel agonist Bay K 8644
      and was decreased by the antagonist nifedipine; and 5) omega-conotoxin had little
      or no effect on the channels. These are properties expected of L-type Ca2+
      channels. 3. To investigate whether these voltage-dependent channels would be
      available for opening on membrane depolarization, we measured the type I cell
      resting membrane potential noninvasively using unitary openings of the L-type
      Ca2+ channel with Bay K 8644 in the cell-attached pipette. Resting potentials
      ranged from -62 to -13 mV, with a mean of -32 mV in 12 cells. 4. Judging from
      single-channel conductance and pharmacology, the Ca2+ current is mostly, if not
      solely, carried by L channels. Thus it should be possible to use modulators of L
      channel activity to determine the role of Ca2+ channels in stimulus-secretion
      coupling in the rat carotid body.

PMID- 7506755
TI  - Hyperpolarization-activated cation current (Ih) in neurons of the medial nucleus
      of the trapezoid body: voltage-clamp analysis and enhancement by norepinephrine
      and cAMP suggest a modulatory mechanism in the auditory brain stem.
AB  - 1. Principal cells in the medial nucleus of the trapezoid body (MNTB) are part of
      a circuit in the superior olivary complex (SOC) that processes binaural
      information important for sound localization. MNTB cells have two voltage
      dependent currents active near rest that contribute to these cells' highly
      nonlinear membrane properties and shape their responses to synaptic input. One of
      these currents, a low-threshold, 4-aminopyridine (4-AP)-sensitive K+ current, has
      been studied previously under current clamp. Using the single-electrode voltage
      clamp technique, we have investigated the other of these currents, a
      hyperpolarization-activated, mixed cation current (Ih), in brain slices of the
      rat SOC. 2. Ih is responsible for a prominent "sag" in the voltage response to a
      steady hyperpolarizing current recorded under current clamp in MNTB cells. In
      voltage-clamp recordings, hyperpolarizing voltage steps from the resting
      potential elicited a large inward current that activated and deactivated with
      biexponential kinetics. Activation time constants were voltage dependent, with
      tau 1 and tau 2 = 246 and 1620 ms at -75 mV and 107 and 560 ms at -100 mV. 3. Ih
      was blocked by 1-5 mM cesium and had a reversal potential of -43 mV. Steady-state
      activation curves derived from tail currents yielded a half-activation voltage of
      -75.7 mV and slope factor of 5.7 mV, corresponding to < 10% activation of Ih at
      rest. 4. Application of norepinephrine (15-20 microM) or 8-bromoadenosine 3',5'
      cyclic monophosphate (8-Br-cAMP) (1 mM) caused a depolarizing shift in the steady
      state activation curve and decreased the activation time constants. The shift in
      the activation curve resulted in a large increase in the activation of Ih at
      rest, an inward shift in the holding current, and an increase in the resting
      membrane conductance. In current-clamp recordings, this increase in the resting
      activation level of Ih resulted in membrane depolarization of 2-3 mV in the
      absence of 4-AP, and 5-10 mV in the presence of 4-AP, an increase in the input
      conductance, and a reduction in the voltage sag in response to hyperpolarizing
      currents. 5. The resulting change in the resting point of MNTB cells exposed to
      norepinephrine or 8-Br-cAMP is likely to alter the responses of these cells to
      synaptic input, both via the direct effect on the resting membrane conductance
      and by changing the activation of the low-threshold, 4-AP-sensitive potassium
      current.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7506756
TI  - Differential neuromodulation of calcium currents by norepinephrine in rat
      sympathetic neurons.
AB  - 1. Differences in the neuromodulation of Ca2+ currents between superior cervical
      ganglion (SCG) and more caudal paravertebral ganglion (PVG) neurons acutely
      isolated from the same rats were investigated using the whole-cell patch-clamp
      technique. 2. Norepinephrine (NE) induced a concentration-dependent inhibition of
      Ca2+ currents in both SCG and PVG neurons. The concentration producing 50%
      inhibition (IC50) for NE estimated from concentration-response curves was similar
      between SCG and PVG neurons but the maximal inhibition estimated from the
      concentration-response curve for PVG neurons was decreased compared with that of
      SCG neurons. 3. Tail current activation curves of both SCG and PVG neurons in the
      absence and presence of NE (5 microM) could be fitted to a double Boltzmann
      equation. In the presence of NE, the activation curves for both SCG and PVG
      neurons were shifted toward more depolarized potentials. The magnitude of the
      shift was greater in SCG than in PVG neurons, which could be accounted for by a
      greater decrease (P < 0.05) in the fractional amplitude of the first current
      component of SCG neurons (delta 1.4 +/- 0.4 nA, mean +/- SE, 39%) compared with
      that of PVG neurons (delta 0.9 +/- 0.1 nA, 16%). 4. Ca2+ current density,
      expressed as maximal tail current amplitude normalized to cell capacitance, was
      greater in PVG neurons than that in SCG neurons. 5. In SCG neurons, a saturating
      concentration of omega-conotoxin GVIA (omega-CgTx) produced a greater decrease of
      Ca2+ current amplitude at +20 mV (77.4 +/- 1.9%) than in PVG neurons (71.2 +/-
      1.5%, P < 0.05). 6. After pretreatment with 15 microM omega-CgTx, NE still
      decreased the Ca2+ currents in both populations of neurons; however, the
      inhibition was greater in SCG neurons (31.1 +/- 3.4%) than in PVG neurons (12.8
      +/- 3.6%, P < 0.01). 7. The dihydropyridine Ca2+ channel "agonist" Bay K 8644 (10
      microM) prolonged Ca2+ tail currents in both SCG and PVG neurons. After
      normalizing to cell capacitance, there was no significant difference in Bay K
      8644-induced tail current amplitude between the two populations of neurons.
      Moreover, NE (5 microM) increased the prolonged Ca2+ tail current amplitude
      induced by Bay K 8644 (10 microM) by 44.7 +/- 13.5% in SCG and 41.9 +/- 11.9% in
      PVG neurons. 8. Under control conditions, Ca2+ currents were facilitated by a
      depolarizing conditioning pulse (50 ms to +100 mV) in both PVG neurons (29.2 +/-
      5.1%) and SCG neurons (20.1 +/- 4.0%).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7506757
TI  - Voltage dependence and activation kinetics of pharmacologically defined
      components of the high-threshold calcium current in rat neocortical neurons.
AB  - 1. As a first step toward identification of the functional significance of the
      spatial distribution of calcium channels we examined the high voltage-activated
      calcium current (HVA current) in acutely isolated pyramidal neurons from rat
      sensorimotor cortex using whole-cell voltage clamp. The goals of this study were
      (1) to determine whether the pharmacologically separable components of the HVA
      current differed in voltage dependence or activation kinetics and (2) to develop
      an empirical model that could predict the HVA current evoked by action potentials
      or other physiological responses. 2. Cells with short dendrites were chosen for
      study. Input resistance averaged 3.5 +/- 0.4 (SE) G omega. Specific membrane
      resistance averaged 51.9 +/- 6.8 K omega-cm2 on the basis of estimated membrane
      surface area. 3. Using 2 mM calcium in the extracellular solution, we evoked the
      HVA current by depolarizations positive to -45 mV from a holding potential of -60
      mV, a potential where the low-threshold calcium current is fully inactivated.
      Maximum HVA current amplitude (484.9 +/- 42.3 pA) occurred near -15 mV. The
      evoked current was completely and reversibly blocked by 200 microM cadmium. 4.
      Tail current amplitude at a fixed potential increased as a sigmoidal function of
      prepulse potential. A plot of normalized tail current amplitude, taken as the
      fraction of HVA channels open at each prepulse potential, was best described by a
      Boltzmann function (maximum slope: e-fold per 11.3 mV; half activation: -24.6 mV)
      raised to the power of 2. This relation was not altered by extracellular
      application of 5 microM nifedipine or 10 microM omega-conotoxin, each of which
      reduced a separate component of the HVA current uniformly at all potentials. We
      conclude that the pharmacologically separable components of the HVA current do
      not differ significantly in voltage dependence. 5. The time course of current
      onset during a step depolarization was best described by second-order activation
      kinetics. Activation time constants ranged from a maximum of 1.2 ms at -40 mV to
      0.3 ms at +25 mV. Neither activation nor tail current time constants were altered
      by extracellular application of 5 microM nifedipine or 10 microM omega-conotoxin.
      After application of 1 microM Bay K 8644 tail current decay was best described by
      a fast time constant similar to control values and a slow time constant. We
      conclude that the pharmacologically separable components of the HVA current in
      these neurons do not differ significantly in kinetics.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7506758
TI  - Voltage-dependent block by neomycin of the ATP-induced whole cell current of
      guinea-pig outer hair cells.
AB  - 1. The effects of externally applied ATP and neomycin on whole cell currents of
      isolated guinea pig cochlear outer hair cells (OHCs) were studied using the whole
      cell voltage-clamp technique. In OCHs held at -70 mV, ATP activated a large
      inward current. In the presence of neomycin, the ATP-induced whole cell current
      activated along a relatively unaltered time course, but the current then
      decreased to a reduced steady level. The neomycin inhibition of the ATP-induced
      current was dose dependent. The half-inhibitory concentration (IC50) of neomycin
      measured at steady state was estimated to be 90 microM. 2. Neomycin inhibition of
      the ATP response could not be reversed by increasing the concentration of ATP,
      indicating that the effect was noncompetitive. The inhibition was voltage
      dependent and was greatly reduced when OHCs were held at positive potentials. 3.
      Cells treated with 100 microM ATP gave maximal current responses. Addition of
      neomycin substantially increased membrane current noise of the 100 microM ATP
      responses. When neomycin concentration was varied from 10 to 500 microM, the
      current noise level peaked between 50 and 100 microM. The noise increase was
      observed at negative holding potentials but not at positive potentials. 4. The
      neomycin-induced whole cell current noise was used to estimate the size of the
      underlying elementary current. The ATP-induced single channel current of OHCs at 
      70 mV was estimated to be approximately 0.3 pA. The number of ATP-activated
      channels in a single OHC was estimated to be in the range of a few thousand. 5.
      The characteristics of the neomycin inhibition of ATP-induced currents were
      consistent with an open channel blocking mechanism. Analysis of the voltage
      dependence of the steady state neomycin inhibition suggested a neomycin binding
      site at an electrical distance of 0.3 from the extracellular side.

PMID- 7506759
TI  - Protein kinase C blocks somatostatin-induced modulation of calcium current in
      chick sympathetic neurons.
AB  - 1. Somatostatin produces a voltage-dependent inhibition of N-type Ca2+ current in
      chick sympathetic neurons. Pretreatment of chick sympathetic ganglion neurons
      with protein kinase C (PKC) activators has no effect on calcium current (ICa) but
      reduces the inhibition of ICa by somatostatin. 2. The effects of the alkaloid PKC
      activator (-)-indolactam V were indistinguishable from those of 4 beta-phorbol-12
      myristate-13-acetate (4 beta-PMA). The inactive isomers (+)-indolactam V and 4
      alpha-PMA did not alter the modulation of ICa by somatostatin. 3. Modulation of
      ICa by somatostatin desensitizes, with a time for half desensitization of
      approximately 3 min. PKC activation mimics the normal desensitization process in
      that responses to 30 nM somatostatin are inhibited to a greater extent than are
      responses to 1 microM somatostatin. 4. PKC appears to act at the level of the
      somatostatin receptor or receptor-G protein interaction because PKC activation
      does not alter Ca2+ current inhibition in response to a nonhydrolyzable analog of
      GTP, GTP-gamma-S, which directly activates G proteins. 5. The specific PKC
      inhibitor calphostin C largely reverses the effects of phorbol esters, but does
      not slow the normal rate of desensitization of somatostatin responses. This
      indicates that PKC is not involved in the homologous desensitization of the
      somatostatin receptor. 6. Neither substance P, which activates PKC in these
      cells, nor arachidonic acid, another PKC activator, altered the action of
      somatostatin on ICa.

PMID- 7506760
TI  - Extracellular cGMP in the hippocampus of freely moving rats as an index of nitric
      oxide (NO) synthase activity.
AB  - The nitric oxide (NO) synthase/cGMP pathway has been studied in vivo in the adult
      rat hippocampus by monitoring the levels of extracellular cGMP during
      microdialysis in conscious unrestrained animals. The basal cGMP efflux was
      concentration-dependently reduced upon local infusion of the NO synthase
      inhibitor NG-nitro-L-arginine (NARG; 10 microM to 1 mM). The NO donors
      hydroxylamine and S-nitroso-N-penicillamine, perfused through the dialysis probe
      at 1 mM, increased by about 200% the extracellular levels of cGMP. The glutamate
      receptor agonist NMDA (125-500 microM) produced concentration-dependent cGMP
      responses that were abolished by the selective receptor antagonist D-2-amino-5
      phosphonovaleric acid or by NARG. Local perfusion of the phosphodiesterase
      inhibitor 3-isobutyl-1-methylxanthine (IBMX; 1 mM) produced a steady eightfold
      increase of extracellular cGMP levels. The effect of IBMX was highly sensitive to
      NARG. The inhibition by NARG of the IBMX-induced cGMP response was reversed when
      the NO synthase substrate L-arginine was administered. It is concluded that cGMP
      collected during in vivo microdialysis reflects NO synthase activity in the rat
      hippocampus. The technique may be utilized to investigate the pathophysiology and
      the pharmacology of the NO/cGMP pathway in the hippocampus of living animals.

PMID- 7506761
TI  - Identification of hair cell progenitors and intermitotic migration of their
      nuclei in the normal and regenerating avian inner ear.
AB  - Postembryonic production of sensory hair cells occurs in both normal and
      aminoglycoside-damaged avian inner ears. The cellular source and mechanism that
      results in new differentiated hair cells were investigated in the avian
      vestibular epithelia using three distinct cell-cycle-specific labeling methods to
      identify proliferating sensory epithelial cells. First, immunocytochemical
      detection of the proliferating cell nuclear antigen, an auxiliary protein of DNA
      polymerase, allowed labeling of cells in late G1, S, and early G2 phases of the
      cell cycle. Second, a pulse-fix tritiated thymidine autoradiographic protocol was
      used to identify cells in S phase of the cell cycle. Finally, Hoechst 33342, a
      fluorescent DNA stain, was used to identify epithelial cells in mitosis. The
      distribution of cells active in the cell cycle within the normal and ototoxin
      damaged vestibular epithelium suggests that supporting cells within the sensory
      epithelia are the cellular precursors to the regenerated hair cells. Differences
      between the proliferation marker densities in control and damaged end organs
      indicate that the upregulation of mitotic activity observed after streptomycin
      treatment is due primarily to an increase in the number of dividing progenitor
      cells. The differences between the extent of ototoxic damage and the level of
      reparative proliferative response suggest a generalized stimulus, such as a
      soluble chemical factor, plays a role in initiating regeneration. Finally, after
      DNA replication is initiated, progenitor cell nuclei migrate from their original
      location close to the basement membrane to the lumenal surface, where cell
      division occurs. This pattern of intermitotic nuclear migration is analogous to
      that observed in the developing inner ear and neural epithelium.

PMID- 7506762
TI  - Autosomal recessive neuromuscular disorder in a transgenic line of mice.
AB  - We have generated a line of transgenic mice that when homozygous for the
      transgene develop a severe, adult-onset neuromuscular disorder. This mutation is
      likely the result of the insertional inactivation of an endogenous gene by the
      transgene integration. The mutant mice have a gait abnormality with stiffened
      and/or splayed hind legs, and adopt a hunched posture with some exhibiting
      kyphosis of the thoracic spine. These symptoms progress gradually to severe motor
      dysfunction. Pathologic changes were found in skeletal muscle and peripheral
      nerve of the mutant animals. In young mice the muscles from both upper and lower
      extremities show necrosis and phagocytosis. In older mice, regeneration with
      muscle fiber splitting, internally located nuclei, and variable fiber size are
      conspicuous features. Interactions between Schwann cells and axons also appear
      disrupted in these animals. Although many peripheral axons are well myelinated,
      the nerve and nerve roots contain very large bundles of juxtaposed, bare axons,
      reminiscent of Schwann cell-axon interactions in early development. Within these
      bundles there are axons large enough to be myelinated. The relationship between
      the pathologic changes in the muscles and nerves is not clear. The phenotypic
      abnormalities of these animals resemble those that occur in the spontaneous mouse
      mutants dystrophia muscularis and myodystrophy. Nevertheless, the chromosomal
      position of the transgene integration site, which was mapped by fluorescent in
      situ hybridization to chromosome 11, indicates that this disorder represents a
      new neuromuscular mutation.

PMID- 7506763
TI  - Activity-dependent retinotopic refinement in a low-density retinotectal
      projection in the goldfish: evidence favoring synaptic cooperation over
      competition.
AB  - During optic nerve regeneration in goldfish, the label from a small retinal spot
      injection of WGA-HRP has been previously reported to be initially widely
      dispersed in the tectum and subsequently to condense into a small patch in the
      retinotopically appropriate location of tectum. This refinement involves two
      separate processes: one is activity independent and generates gross retinotopy;
      the other is activity dependent and mediates the formation of fine retinotopy.
      Since the number of synapses remains constant during this refinement, one or both
      of these processes may involve some form of competition for a limited number of
      synaptic sites. To clarify the role of synaptic competition, we created a low
      density retinotectal projection in goldfish by deflecting about 20% of the optic
      fibers from one tectum into the opposite tectum, which was denervated of all
      other optic fibers. Under this condition, it was previously shown that less than
      half the normal density of synapses is formed. If competition for synaptic sites
      is a requirement of refinement, refinement should be prevented or significantly
      hindered. To monitor refinement during regeneration, 2 nl spot injections of WGA
      HRP were made into the retina at various times after deflection. To distinguish
      between activity-dependent and activity-independent refinement, retinal impulse
      activity was blocked in some fish with repeated injections of TTX into the eye
      for the duration of the experiment. It was found that considerable activity
      independent refinement occurred under continuous TTX blockade although the fibers
      remained more dispersed than in previous TTX studies when normal numbers of
      fibers were present. Surprisingly, in fish with normal impulse activity, the
      degree of activity-dependent refinement was almost normal. Labeled fibers
      condensed into a small area roughly comparable in size to that observed when the
      full complement of fibers was regenerating into tectum. These results suggest
      that competition for limited synaptic sites is not essential for activity
      dependent refinement, which may, instead, be mediated by a cooperative process
      that actively promotes convergence. The findings further suggest that if synaptic
      competition plays a role in this system, it is in regulating activity-independent
      mechanisms that determine the large-scale distribution of fibers within tectum.

PMID- 7506764
TI  - Neuronal characterization, compartmental distribution, and activity-dependent
      regulation of glutamate immunoreactivity in adult monkey striate cortex.
AB  - Monospecific antibodies to glutamate were used to characterize the organization
      of excitatory neurons and the plasticity of glutamate expression in the macaque
      striate cortex. Somata and processes immunoreactive for glutamate were densely
      and unevenly distributed in layers II-III, IVA, IVC. In tangential sections
      through layers II and III, patches of intense glutamate immunostaining were
      observed and were found to coincide with regions of the cytochrome oxidase (CO)
      rich puffs. By contrast, clusters of intense immunostaining were surrounded by
      the lightly immunostained but intensely CO-stained lattice in layer IVA.
      Similarly, in layer IVC, focal aggregates of intense glutamate immunoreactivity
      were interspersed among regions of light immunostaining but intense CO staining.
      Glutamate immunoreactivity was also intense in layer VI but was much lighter in
      layers I, IVB, and V. Throughout the striate cortex, neurons resembling pyramidal
      cells and spiny stellate cells and processes that included dendrites and axons
      were immunostained. None of the glutamate-positive neurons was GABA
      immunoreactive. Following monocular deprivation of adult monkeys by intravitreal
      injections of TTX into one eye, glutamate immunoreactivity in layers IVC was
      distributed in alternating intensely and lightly stained stripes. The stripes of
      reduced immunostaining, which contained an abnormally low concentration of
      glutamate neurons and pale neuropil, corresponded to columns dominated by the TTX
      injected eye. Similar stripes of alternating intense and light immunoreactivity
      were seen in layers II-III, where they corresponded to rows of puffs at the
      centers of intact-eye and deprived-eye columns, respectively. These findings
      demonstrate that glutamate-immunoreactive neurons and terminals in monkey striate
      cortex are densely concentrated in layers receiving direct geniculocortical
      innervation. In addition, the glutamate neurons and terminals form discrete
      units, which in layers II and III coincide precisely with regions receiving
      geniculocortical terminations but in layers IVA are segregated from these
      terminations. The findings also indicate that glutamate immunoreactivity is
      regulated by visually driven activity, and suggest that monocular deprivation in
      adulthood leads to a reduction in the major excitatory neurotransmitter in visual
      cortex as well as previously indicated reductions in GABA, the major inhibitory
      neurotransmitter.

PMID- 7506765
TI  - Nitric oxide-dependent efflux of cGMP in rat cerebellar cortex: an in vivo
      microdialysis study.
AB  - The stimulation of excitatory amino acid receptors in the cerebellar cortex
      results in the Ca2+/calmodulin-dependent activation of nitric oxide synthase.
      This leads to an increase in tissue levels of cGMP following the interaction of
      nitric oxide with soluble guanylyl cyclase. The cerebellar cortex has the highest
      levels of nitric oxide synthase and cGMP in the brain; however, the levels of
      guanylyl cyclase and cGMP-phosphodiesterase are remarkably low. Thus, the
      mechanisms regulating cGMP levels in cerebellar cells are unclear. One report has
      noted that cGMP can be released from cerebellar slices. We have therefore used
      intracerebellar microdialysis in awake, freely moving rats to test the hypothesis
      that activation of nitric oxide synthase in the cerebellar cortex results in the
      release of cGMP. Climbing fibers, which release excitatory amino acids in the
      cerebellum, were activated with systemic harmaline. This resulted in an immediate
      increase in extracellular cGMP, which was blocked by TTX or the removal of
      extracellular Ca2+, and attenuated by prior lesion of the climbing fibers.
      Blockade of N-type calcium channels with omega-conotoxin also antagonized the
      harmaline-induced increase. In contrast, blockade of L-type calcium channels, or
      inhibition of anion transport with probenecid or bromosulfophthalein, potentiated
      the increase in cGMP seen in response to harmaline. Inhibitors of nitric oxide
      synthase or guanylyl cyclase prevented the harmaline-induced increase in
      extracellular cGMP, while phosphodiesterase inhibitors potentiated the increase.
      Local application of the NMDA antagonist 2-amino-5-phosphonopentanoic acid or the
      AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione attenuated the
      effect of harmaline.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506766
TI  - Increased transmitter release at excitatory synapses produced by direct
      activation of adenylate cyclase in rat hippocampal slices.
AB  - The field EPSP recorded in the CA1 region of rat hippocampal slices is
      potentiated by bath application of the direct adenylate cyclase activator
      forskolin (Chavez-Noriega and Stevens, 1992a). We have now used the whole-cell
      patch-clamp technique to analyze the effect of forskolin on evoked synaptic
      currents and on spontaneous and miniature excitatory postsynaptic currents
      (sEPSCs and mEPSCs) recorded in rat hippocampal slices in order to determine the
      relative contributions of pre- and postsynaptic mechanisms to this increased
      synaptic strength. Application of 50 microM forskolin in the presence of 3
      isobutyl-1-methylxanthine (IBMX; a phosphodiesterase inhibitor) enhanced the
      evoked EPSC (eEPSC) peak amplitude to 230 +/- 43% of control (n = 13). No
      significant change in sEPSC or in mEPSC amplitude was detected after forskolin
      addition (106 +/- 7%, n = 9), indicating that postsynaptic receptor sensitivity
      at synaptic junctions is not greatly affected. In contrast, a large increase in
      sEPSC and mEPSC frequency was noted in all cells (299 +/- 81%). Following
      forskolin application, the amplitude distribution of evoked synaptic currents
      shifted to larger values, but more significantly, a sharp decrease in failure
      rate was produced in all cells tested. Also, a significant correlation was found
      between the potentiation produced by forskolin in IBMX on the eEPSC and the ratio
      of the squared coefficient of variation (CV = SD/mean). Finally, a quantal
      analysis of four cells was consistent with the hypothesis that transmitter
      release was increased by forskolin/IBMX with, if anything, a concomitant decrease
      in quantal size. Together, these observations indicate that presynaptic
      mechanisms significantly contribute to the enhancement produced by this
      diterpene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506767
TI  - Preparation and application of monoclonal antibodies for a sandwich enzyme-linked
      immunosorbent assay of the major soybean allergen, Gly m Bd 30K.
AB  - In order to obtain probes suitable for the determination of the major soybean
      allergen, Gly m Bd 30 K, in soybean-related processed foods, we have prepared two
      monoclonal antibodies, F5 of IgG2a and H6 of IgM, by the fusion of P3U1 myeloma
      cells with the spleen cells of BALB/c mice immunized with the reductively
      carboxymethylated allergen (RCM-allergen). The two monoclonal antibodies were
      shown to be specific to the intact allergen as well as the RCM-allergen and to
      recognize distinct epitopes on the allergen. Of the monoclonal antibodies, F5 was
      conjugated with peroxidase. H6 and the labeled F5 were applied as the fixing
      antibody and the labeled first antibody, respectively, for a direct sandwich
      enzyme-linked immunosorbent assay of the allergen. When the allergen was
      extracted from the soybean-related foods with Tris-HCl buffer containing sodium
      dodecylsulfate and mercaptoethanol, the allergen, Gly m Bd 30 K, was shown to be
      measured in a range of 5-500 ng in this assay.

PMID- 7506768
TI  - Primary culture of microvascular endothelial cells from canine meniscus.
AB  - Microvascular endothelial cells were isolated and cloned from canine knee
      menisci. Initially, the endothelial cell colonies in culture exhibited a
      cobblestone morphology. With passage and time, these cultures adopted a
      fibroblastic or fusiform morphology. The endothelial nature of the cells was
      demonstrated by positive immunostaining with antibodies to von Willebrand factor,
      laminin, and type-IV collagen and by capillary-like tube formation on Matrigel.
      These endothelial cells could be passaged as many as 10 times with retention of
      the endothelial characteristics. This population of meniscal microvascular
      endothelial cells will facilitate studies on the role of blood vessels in
      meniscal repair.

PMID- 7506769
TI  - [Six cases of anesthesia mumps].
AB  - Six cases of acute transient enlargement of the parotid gland under general
      anesthesia, so called anesthesia mumps, are reported. Patient 1 was placed in the
      left lateral position and the left parotid gland was subsequently observed to be
      diffusely enlarged. With five patients in the prone position, bilateral parotid
      gland enlargement was observed. Patient 1 complained of parotid swelling. Patient
      4 suffered from slight tenderness of the right parotid gland. However, the others
      had no subjective symptoms. All cases of parotid swelling resolved spontaneously
      within 7 days. Changes in serum amylase during parotid enlargement were almost
      within normal range. Mechanical compression by sheet amadou may have produced the
      swelling in the patient who was placed in a lateral position. In the prone
      position, changes in the autonomic nervous system during surgical procedures and
      anesthesia, vascular congestion resulting from the surgical position, an
      overactive pharyngeal reflex stimulated by endotracheal intubation and mechanical
      ventilation are discussed as possible causes. Evaluation of the occurrence and
      clinical course of anesthesia mumps provided useful diagnostic and management
      data.

PMID- 7506770
TI  - Vascular activation in the histopathogenesis of Hodgkin's disease: potential role
      of endothelial tissue factor in intravascular thrombosis and necrosis.
AB  - Endothelial cell activation and alterations of intravascular coagulation were
      investigated in 27 cases of Hodgkin's disease (HD), in five cases of anaplastic
      large cell lymphoma (ALCL), and in ten reactive lymph nodes. Lymph node sections
      were immunostained for E-selectin, a molecule present on cytokine-activated
      endothelial cells; for tissue factor (TF), a cellular initiator of the
      coagulation cascade; for glycoprotein (gp) II/III, a platelet-specific antigen;
      and for fibrin. In HD, vascular activation was particularly prominent in the
      nodular sclerosis subtype, as indicated by a larger number of E-selectin-positive
      blood vessels (72 +/- 49) compared with mixed cellularity (22 +/- 37). High
      expression of E-selectin was associated with alterations of intravascular
      coagulation, as indicated by immunostaining of some vascular endothelial cells
      for TF, by a higher incidence of intravascular thrombi, and by the extensive
      presence of areas of fibrin exudation and necrosis. In ALCL, the levels of
      endothelial cell activation and intravascular coagulation were comparable to
      those of HD nodular sclerosis. In reactive nodes, some E-selectin-positive blood
      vessels were observed only in 3/10 cases; immunostaining for TF was not detected
      on endothelial cells; and alterations of intravascular coagulation were rarely
      observed.

PMID- 7506772
TI  - Immunohistochemical detection of CD1A antigen in formalin-fixed and paraffin
      embedded tissue sections with monoclonal antibody 010.
AB  - The immunoreactivity of a CD1a monoclonal antibody (MAb), denoted 010, was
      investigated by means of the streptavidin-biotin-peroxidase method in formalin
      fixed and paraffin-embedded tissues from 47 cases. The samples comprised reactive
      lymphoid proliferations of skin, tonsil, and lymph node including dermatopathic
      lymphadenopathy and Langerhans' cell histiocytosis, Hodgkin's and non-Hodgkin's
      lymphomas, and thymomas. Interdigitating and dermal dendritic cells, veiled
      cells, Langerhans' cells, and also cortical thymocytes and their neoplastic
      counterparts displayed immunostaining with MAb 010 in paraffin sections. These
      results are identical to previous ones reported for other CD1a MAbs in fresh or
      frozen specimens. The findings suggest that the binding site of 010 is a fixation
      resistant epitope of CD1a antigen which has not been previously identified.

PMID- 7506771
TI  - Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections.
AB  - Enzymatic and non-enzymatic treatments for antigen unmasking on formalin-fixed,
      paraffin-embedded, dewaxed sections were optimized and compared by the use of a
      panel of antibodies of diagnostic relevance (anti-cytokeratins, vimentin, S-100,
      T- and B-cell receptors, Ki-67/MIB 1, muscle actin). Non-enzymatic unmasking was
      obtained by boiling the slides in a microwave oven in 0.01 M salt solution (pH 6)
      or in 6 M urea. Trypsin or pronase digestion was used for comparison and found to
      be necessary for some of the reagents. The investigation was then extended to 256
      antibodies; the epitopic amino acid sequence was known for 48 of them. We found
      that enzymatic and non-enzymatic antigen unmasking are not dependent on the
      epitope sequence, but some antigens benefit selectively from one treatment but
      not from the other. Denaturation of proteins is the likely mechanism which leads
      to immunodetection on microwave oven-boiled slides; this suggestion is supported
      by the use of denaturating solutions and by the observation that endogenous
      enzymes were inactivated and a few antigens were no longer immunodetectable after
      boiling. Non-enzymatic methods for antigen unmasking are a powerful new tool for
      broadening the use of antibodies for immunostaining formalin-fixed, paraffin
      embedded sections and should be used in parallel with the traditional enzymatic
      methods.

PMID- 7506773
TI  - Assessment of young children with a suspected disability.

PMID- 7506774
TI  - Prevalence and impact of multiple childhood chronic illnesses.
AB  - OBJECTIVE: To determine the prevalence and impact of multiple chronic conditions
      on children's health status and utilization of health services. DESIGN: Analysis
      of the 1988 National Health Interview Survey on Child Health. SETTING: Nationally
      representative sample of the U.S. civilian, noninstitutionalized population.
      PARTICIPANTS: A total of 17,710 children less than 18 years of age selected in a
      stratified cluster sampling of U.S. households. INTERVENTION: None. RESULTS: We
      estimated that fewer than 5% of children have multiple (two or more) chronic
      conditions and that less than 1% of children had three or more such conditions.
      However, despite this low overall prevalence, some notable features of multiple
      chronic conditions stand out. Many of the most prevalent condition-pairs were
      allergy related, and the rates of co-occurrence of these disorders were generally
      higher than would be predicted on the basis of prevalence rates for the
      individual conditions. Children with multiple chronic conditions had more mental
      and physical health problems and used substantially more health services than
      other children. For example, the prevalence of developmental delay, learning
      disabilities, and emotional and behavioral problems increased sharply with the
      number of chronic conditions reported. Notable deterioration in such health
      status measures as days in bed, school absences, and activity limitation was also
      observed with increasing numbers of chronic conditions. Similarly, utilization of
      hospital and physician services increased in tandem with increasing numbers of
      chronic conditions. CONCLUSIONS: Children who have multiple conditions of a
      chronic nature, even if few in number, have increased morbidity across a variety
      of measures.

PMID- 7506775
TI  - Sensitisation of Candida albicans to killing by low-power laser light.
AB  - The purpose of this study was to determine whether Candida albicans, and other
      Candida spp. responsible for HIV-associated candidosis, could be sensitised to
      killing by low-power laser light. Suspensions of C. albicans were treated with a
      number of potential photosensitisers, exposed to laser light from a Helium/Neon
      (HeNe) or Gallium aluminium arsenide (GaAs) laser for 120 s and survivors
      enumerated. Toluidine blue O (TBO), thionin and crystal violet were able to
      sensitise the yeast to killing by light from the HeNe laser (energy dose = 876 mJ
      at a density of 66.36 J/cm2), the kills achieved being 6.8 x 10(6) cfu/ml, 3.1 x
      10(6) cfu/ml and 1.3 x 10(6) cfu/ml respectively. TBO was also able to sensitise
      several other Candida spp. to killing by HeNe laser light. Dihaematoporphyrin
      ester was not an effective photosensitiser under the conditions employed.
      Methylene blue, but not aluminium disulphonated phthalocyanine, was able to
      sensitise C. albicans to killing by light from the GaAs laser (energy dose 1.32 J
      at a density of 2.04 J/cm2). The viability of the yeast was not affected by
      exposure to laser light in the absence of the photosensitisers. As killing of dye
      sensitised C. albicans, and other Candida spp., could be achieved by exposure to
      low-power laser light for short periods of time, this approach merits further
      investigation as a potential therapeutic modality for HIV-associated candidosis.

PMID- 7506777
TI  - College position paper: HRT and the surgeon.

PMID- 7506778
TI  - The Royal College of Surgeons of Edinburgh. Position paper on junior doctors'
      hours: the new deal.

PMID- 7506776
TI  - Discrimination of parakeratinised odontogenic keratocysts from other odontogenic
      and non-odontogenic cyst types by expression of a 38kd cell-surface glycoprotein.
AB  - We have identified strong expression of a 38-kD cell surface glycoprotein (gp38),
      a marker of basal cell carcinomas (BCCs), in basal and suprabasal epithelial cell
      membranes of parakeratinised odontogenic keratocysts. In contrast,
      orthokeratinised cysts and most other odontogenic cyst types, ameloblastomas,
      normal stratified oral epithelium, cell rests of Malassez and glands of Serres,
      all proved negative. To our knowledge this is the first histochemical marker to
      distinguish between these major cyst types. It has obvious uses in the diagnosis
      of inflamed keratocysts and the separation of ameloblastomas from BCCs and may
      find a role in studies of the developmental biology of other odontogenic
      structures.

PMID- 7506779
TI  - Women in surgery in Scotland. A Working Party of the Royal College of Surgeons of
      Edinburgh.
AB  - Despite the fact that 50% of medical undergraduates are female, women comprise
      fewer than 1% of consultant general surgeons. The possible reasons for this were
      addressed by a working party of the Royal College of Surgeons of Edinburgh, which
      now reports the results of a survey of 35 women surgeons of SHO 3 grade and above
      working in Scotland. Findings were compared with those of 12 anaesthetists and 10
      house officers. Surgeons had had an accurate perception of the work patterns
      their job would entail but no preparation for the lifestyle implications. The
      experience of gender discrimination was similar in all three groups but perceived
      discrimination was much more prevalent among surgeons/ophthalmologists. In
      contrast to the other groups surveyed, the surgical cohort was not deterred by
      training length, but rather discouraged by the lack of responsibility offered.
      Other factors which seem to contribute to the underrepresentation of women among
      surgeons may be the lack (1) of time for child rearing and (2) of same-sex role
      models.

PMID- 7506780
TI  - Three-dimensional endoscopic imaging for minimal access surgery.
AB  - Three-dimensional endoscopic imaging (3DEndoImaging) is a significant
      technological advance and has the potential to make minimal access surgery (MAS)
      easier, quicker, less prone to error and more applicable to advanced procedures.
      Surgeons involved in MAS will need to have a working knowledge of 3DEndoImaging.
      This article will enable surgeons to compare stereo systems and evaluate which
      system would best suit their needs. This paper explains why stereo imaging is
      important and describes the methods by which stereo images can be produced. The
      technology required is discussed in simple terms. The types of stereo systems are
      described and important operational and maintenance issues discussed. Task
      analysis studies showing significant improvement in performance in stereo are
      presented. These studies simulated accurately positioning an instrument and
      threading a small diameter solder lug.

PMID- 7506781
TI  - Abdominal tuberculosis: a study of 881 cases.
AB  - A retrospective study of the epidemiological pattern of abdominal tuberculosis in
      Ibadan, Nigeria during the 30-year period 1960-1989 has been completed. Among 881
      cases seen (355 men and 526 women), children under 10 years represented 10.5% of
      cases but 78% of all cases were under 40 years. Women accounted for 64% of this
      number. The peak age incidence was 21-30 years (30.1%). Over 40 years of age, the
      female incidence fell (9%), so that the male incidence became greater (12%). The
      population-adjusted annual incidence during the 30-year period showed a gradual
      decline during the first two decades but a rising trend in the last decade is now
      evident. The clinical and pathological features were similar to those previously
      described, but delay in presentation varied between 1 and 14 1/2 months with a
      mean (SEM) of 5.2 (1.3) months.

PMID- 7506782
TI  - Obstructive colonic cancer.
AB  - The records of 121 patients with obstructing cancer of the colon were reviewed.
      About one-third of the patients had metastatic disease at the time of operation.
      Primary resection and anastomosis of the intestine was performed for most cancers
      of the ascending or transverse colon. Hartmann's procedure was performed in most
      patients with cancer of the sigmoid colon and rectum. Wound infection occurred in
      20 patients (16.5%) and anastomotic leakage in six (4.9%). The operative
      mortality rate was 14.9%. The 5-year survival rate was 13.5%. Acute colonic
      obstruction is associated with high morbidity and mortality. The high incidence
      of advanced disease, advanced age, delay in tumour excision and unprepared bowel
      are some of the factors resulting in the poor prognosis of these patients.

PMID- 7506783
TI  - Pyloromyotomy: why make an easy operation difficult?
AB  - Recently Ohri et al. advocated a modification to the standard pyloromyotomy for
      pyloric stenosis which they believed reduced postoperative vomiting. Their study
      had no control group to support their contention. We therefore compared 37
      infants with hypertrophic pyloric stenosis who underwent a conventional
      longitudinal pyloromyotomy with the 37 infants reported by Ohri et al. who
      underwent a modified Ramstedt's pyloromyotomy. Data were recorded prospectively
      and the postoperative vomiting was assessed using the same scale as in the
      previous report. The incidence of vomiting was significantly less in the children
      undergoing the conventional operation (P = 0.03), suggesting that there is no
      justification for performing a double V-shaped pyloric incision in pyloric
      stenosis.

PMID- 7506784
TI  - Closed intramedullary osteotomy for the correction of deformities of the femur.
AB  - Over the period 1986-1990, an intramedullary saw was used to correct length
      inequality, rotational and axial deformities and malunions of 17 femora in 15
      patients. Interlocking intramedullary nails were inserted after the osteotomies
      were performed. No postoperative complications were encountered. Quadriceps
      function returned within 2-8 days and all osteotomies healed radiographically
      within 3 months. All deformities were satisfactorily corrected and all patients
      were pleased with the outcome. The intramedullary nails were removed in the
      majority one year following surgery. The authors conclude that closed
      intramedullary osteotomy of the femur is a safe and effective technique to
      correct deformities of the femur, although demanding in terms of experience and
      equipment.

PMID- 7506785
TI  - ASAP total knee arthroplasty instrumentation: all six, all precise?
AB  - Thirty consecutive cases requiring total knee replacement (TKR) were treated
      using the Richards Tricon Total Knee System with ASAP (All Six, All Precise)
      instrumentation (Richards Medical Company, Memphis, TN, USA). Preoperative and
      postoperative overall coronal alignment were measured using long-leg
      anteroposterior X-rays. The femoral and tibial bone cuts in this plane were
      assessed using intraoperative films. The aim was to achieve a postoperative
      coronal tibio-femoral alignment of 7 degrees valgus. The mean preoperative
      alignment was 1 degree valgus (SD = +/- 13.5 degrees). A mean postoperative
      alignment of 8 degrees valgus was obtained (SD = +/- 5.6 degrees). The results
      obtained in this series suggest that the ASAP system with careful use simplifies
      the technique of total knee replacement while maintaining accuracy.

PMID- 7506786
TI  - Treatment of grade III osteonecrosis of the femoral head with a
      Charnley/Bicentric hemiarthroplasty.
AB  - Thirty-eight hips with Charnley/Bicentric hemiarthroplasties were reviewed.
      Preoperatively all hips had a Grade III osteonecrosis (Arlet & Ficat) of the
      femoral head. Follow-up ranged from 42 to 72 months with a mean of 56 months. The
      mean age was 36 years (range 16-52 years). Three hips with gross loosening of the
      femoral prosthesis were revised to a cementless total hip replacement: a further
      two hips exhibited radiological changes indicative of loosening and pending
      failure. In one hip with progressive loss of joint space and secondary
      degenerative changes the Bicentric cup was revised to a cemented Charnley
      component. Acetabular migration was not encountered. Six of 38 hips (15.8%) were
      thus considered failures. The mean total movement from full abduction to full
      adduction at the cup-acetabular articulation was 21 degrees, compared to 14
      degrees at the inner component articulation. The results of cemented femoral
      components are predictably unfavourable in this young age group. However, the
      double articulation of the bipolar cup offers an acceptable method of treatment
      for this grade of osteonecrosis in the medium term.

PMID- 7506788
TI  - Fine needle aspiration cytology.

PMID- 7506787
TI  - Which tests to choose when assessing hand function.
AB  - In an attempt to simplify the choice of the many tests available for the
      assessment of hand function nine commonly used tests assessing different
      modalities of hand function have been evaluated on a small group of patients. The
      tests are judged by how well they fulfil the criteria of being simple and quick
      to use, easy to replicate, relevant to the needs of the patient, objective and
      inexpensive to acquire. The five tests which most fulfilled these criteria have
      been used to form a concise and practical hand assessment pro forma.

PMID- 7506789
TI  - Investigation of cervical lymphadenopathy presumed to be metastatic in nature: a
      review of current clinical practice.

PMID- 7506790
TI  - Enhancement of fluorescein perfusion in experimental skin flaps following
      postischemic washout with iloprost, urokinase, verapamil, and University of
      Wisconsin solution.
AB  - The enhancement of blood flow in experimental skin flaps following postischemic
      perfusion washout was investigated in rats. Unilateral island skin flaps based on
      the superficial epigastric vessels were raised and subjected to 6 hr of primary
      ischemia. Group 1 was designated as a control and did not undergo postischemic
      perfusion washout. In the remaining rats, postischemic washout was performed with
      one of five agents: Group 2--lactated Ringer's solution; Group 3--University of
      Wisconsin solution, an organ preservation medium; Group 4--verapamil, a calcium
      channel blocker; Group 5--urokinase, a thrombolytic agent; Group 6--iloprost, a
      stable prostacyclin analog. Two hours following perfusion washout, fluorometric
      analysis revealed a statistically significant enhancement of blood flow in Groups
      4, 5, and 6, compared to Groups 2 and 3 (p < 0.05). Furthermore, a significant
      increase in skin surface fluorescence was demonstrated in all the flaps that
      underwent perfusion washout, compared to the control flaps (p < 0.05). By
      analyzing skin surface fluorescence, the enhancement of nutritive blood flow in
      flaps, following postischemic perfusion washout, was evaluated. This is the first
      study in which the above pharmacologic agents were compared in a quantitative
      manner.

PMID- 7506791
TI  - Comparison of the ontogeny of specific cell surface determinants on normal and
      delayed implanting mouse embryos.
AB  - The ontogeny of immunospecific cell surface determinants on preimplantation mouse
      embryos was determined by means of an antibody-dependent complement-mediated cell
      lysis assay. The determinants conferring sensitivity to lysis in that assay were
      first observed at the late blastocyst stage on embryos recovered from normal
      pregnancy on day 5 or grown to an equivalent stage in vitro. Although blastocysts
      recovered during the dormant phase associated with delayed implantation were not
      lysed, those recovered following reactivation with an injection of oestrogen to
      the mother were sensitive. Furthermore, it was found that treating the dormant
      embryos with neuraminidase rendered them sensitive to lysis. These results
      demonstrate that the appearance of specific cell surface determinants on mouse
      embryos is temporally associated with the process of attachment to the uterus in
      both normal pregnancy and at termination of the dormant phase associated with
      delayed implantation. They also indicate that those determinants may be 'masked'
      with sialic acid during embryonic diapause. It is suggested that such cell
      surface determinants could be important for embryo attachment and that the
      mechanism responsible for their expression may explain some aspects of the
      synchronization between the preimplantation conceptus and its mother at the time
      of implantation.

PMID- 7506792
TI  - Failure of sheep-goat hybrid conceptuses to develop to term in sheep-goat
      chimaeras.
AB  - Six hybrid pregnancies were established: three in sheep-goat chimaeras, one in a
      sheep-(sheep-goat)hybrid chimaera and two in does. Pregnancies were monitored
      weekly by ultrasonography and peripheral concentrations of pregnancy specific
      protein B (PSPB) were measured. Placental development as detected by
      ultrasonography appeared to be slower in hybrid-in-goat pregnancies than in
      hybrid-in-chimaera pregnancies, although this difference was not reflected in
      PSPB concentrations. Time of fetal death could not be predicted from PSPB
      concentrations. Chimaeras appeared to carry hybrid pregnancies longer than ewes
      and does usually carry hybrid pregnancies, but none was carried to term.

PMID- 7506793
TI  - Effects of cryopreservation on the human sperm acrosome and its response to
      A23187.
AB  - The proportion of human spermatozoa from 28 ejaculates to lose their acrosomes
      during cryopreservation was measured and correlated with the number that became
      immotile or lost the integrity of their plasma membrane. The ability of washed
      spermatozoa to acrosome react in response to A23187 before and after
      cryopreservation was compared. Motility was assessed by time-lapse photography;
      intact acrosomes were stained with fluorescein conjugated Pisum sativum
      agglutinin and dead spermatozoa were stained with bisbenzimide (H33258). Twenty
      four per cent of spermatozoa lost their acrosomes during freezing and thawing,
      but the number that did so was not correlated with the number that became
      immotile or non-viable. Frozen spermatozoa exhibited fewer spontaneous acrosome
      reactions than did fresh spermatozoa (5 versus 13% after 4 h), but they responded
      to A23187 in a similar way. Although frozen spermatozoa were significantly more
      likely to die during the incubation, the data do not suggest that degenerative
      acrosome loss had a major influence on the results. In the hamster egg test
      frozen-thawed spermatozoa achieved more penetrations than did fresh spermatozoa
      when stimulated with 0 or 1 mumol A23187 l-1 but considerably fewer when
      stimulated with 4 mumol A23187 l-1. The following conclusions were made. First,
      cryopreservation damage to the acrosome, the plasma membrane and the flagellum
      can occur independently. Second, acrosome function is maintained after
      cryopreservation as long as the organelle remains mechanically intact. Third,
      some spermatozoa that lose their acrosomes during cryopreservation remain viable
      and can fuse with zona-free hamster eggs.

PMID- 7506794
TI  - Surprising activity of flutamide withdrawal, when combined with
      aminoglutethimide, in treatment of "hormone-refractory" prostate cancer.
AB  - BACKGROUND: The best treatment for patients with "hormone-refractory" metastatic
      prostate cancer is unclear, particularly in patients for whom suramin and
      hydrocortisone have failed. PURPOSE: We investigated a combination of flutamide
      withdrawal and aminoglutethimide in suramin- and hydrocortisone-pretreated
      patients with "hormone-refractory" prostate cancer. METHODS: Twenty-nine patients
      with metastatic prostate cancer were treated with simultaneous flutamide
      withdrawal and aminoglutethimide (250 mg given orally four times daily). All
      patients were taking flutamide at the time of entry, and previous treatments with
      medical or surgical castration, flutamide, suramin, and hydrocortisone had failed
      in all of these patients. Because of suramin-induced adrenal insufficiency, all
      patients had previously received, and continued to receive, physiological doses
      of hydrocortisone. Treatment of all non-surgically castrated patients had
      previously failed; however, these patients continued to receive depot leuprolide.
      RESULTS: In 14 (48%) of 29 patients, the prostate-specific antigen (PSA)
      decreased by more than 80% for 4 or more weeks. Improvements in anemia,
      thrombocytopenia, soft-tissue masses, bone scans, and symptoms were also noted.
      Factors associated with response included prolonged flutamide pretreatment, a
      markedly elevated pretreatment PSA, and the absence of soft-tissue disease.
      CONCLUSIONS: Flutamide withdrawal, when combined with the simultaneous
      administration of aminoglutethimide, is a therapeutically active approach in
      patients with "hormone-refractory" prostate cancer. IMPLICATIONS: On the basis of
      these and additional data, we hypothesize that prolonged exposure to flutamide
      results in the selective proliferation of cancer cells containing a mutant
      androgen receptor that aberrantly recognizes flutamide metabolites and
      nonandrogenic steroids as androgenic stimuli.

PMID- 7506795
TI  - Phenotype and function of peripheral and prostatic lymphocytes in patients with
      benign prostatic hyperplasia.
AB  - In a previous report, we demonstrated intense lymphocytic infiltration of all
      benign prostatic hypertrophy (BPH) tissues analyzed in conjunction with HLA-DR
      expression on normally MHC-class-II-negative prostate epithelial cells. The
      composition of these infiltrates (70 to 80% CD3+ T-cells, but no granulocytes)
      resembles the situation seen in immune responses against altered self or self
      rather than against foreign antigens (infection). In the present study,
      phenotypic and functional immunoassays were used in order to investigate whether
      T-cells in BPH are indeed activated, and whether this activation is systemic or
      restricted locally to the prostate. Analysis of T-cell activation marker
      expression and proliferation requirements provided substantial evidence that
      these infiltrating lymphocytes, in contrast to their peripheral counterparts, are
      chronically activated. Since local accumulation of activated lymphocytes can
      cause tissue destruction, high concentrations of cytokines, and consequently
      tissue rebuilding, this process might contribute to the pathogenesis of BPH.

PMID- 7506796
TI  - Hyponatremic encephalopathy after endometrial ablation.

PMID- 7506797
TI  - Pathologic and clinical findings to predict tumor extent of nonpalpable (stage
      T1c) prostate cancer.
AB  - OBJECTIVES: We examined preoperative clinical and pathologic parameters in men
      with clinical stage T1c disease who underwent radical prostatectomy and
      correlated these findings with the pathologic extent of disease in the surgical
      specimen in an attempt to identify a subset of patients with potentially
      biologically insignificant tumor who might be followed up without immediate
      treatment. DESIGN AND PATIENTS: A case series of 157 consecutive men who
      underwent radical prostatectomy for clinical stage T1c disease compared with 64
      similarly treated clinical stage T1a cancers (incidental minimal cancers found on
      transurethral resection of prostate) and 439 clinical stage T2 (palpable)
      cancers. MAIN OUTCOME MEASURES: Pathologic stage, grade, and margins; tumor
      volume; and tumor location. RESULTS: Sixteen percent of tumors were insignificant
      (< 0.2 cm3 and confined to the prostate, with a Gleason score < 7); 10% were
      minimal (0.2 to 0.5 cm3 and confined to the prostate, with a Gleason score < 7);
      37% were moderate (> 0.5 cm3 or capsular penetration, with a Gleason score < 7);
      and 37% were advanced (capsular penetration, with a Gleason score > or = 7 or
      positive margins, seminal vesicles, or lymph nodes). These findings are
      intermediate between those found in clinical stage T1a and stage T2 disease. The
      following parameters were not predictive of tumor extent: age, reason for
      evaluation, method of detection, and transrectal ultrasound. The best model
      predicting insignificant tumor was prostate-specific antigen (PSA) density less
      than 0.1 ng/mL per gram and no adverse pathologic findings on needle biopsy, or
      PSA density of 0.1 to 0.15 ng/mL per gram, with a low- to intermediate-grade
      cancer smaller than 3 mm found in only one needle biopsy core specimen. The
      positive predictive value of the model was 95%, with a negative predictive value
      of 66%. We accurately predicted 73% of cases with insignificant tumor.
      CONCLUSIONS: Eighty-four percent of nonpalpable prostate cancers diagnosed by
      screening techniques are significant tumors and warrant definitive therapy.
      However, 16% are insignificant. Serum PSA level, PSA density, and needle biopsy
      pathologic findings are accurate predictors of tumor extent. It may be reasonable
      to follow up some patients whose tumors are most likely insignificant with serial
      PSA measurements and repeated biopsies.

PMID- 7506798
TI  - [Anti-Hp antibody may vary with strain used as antigen possibly due to
      serological diversity].
AB  - Western blotting and ELISA techniques have been used to investigate antigen
      specificity of systemic responses. Immunoblotting studies demonstrate several
      major protein antigens that are detected most sera. H. pylori immunoblotting
      studies using rabbit hyperimmune sera identify several distinct strains. Seven
      monoclonal antibodies which are prepared in our laboratory recognize 33-35 kDa
      and 66 kDa of H. pylori. ELISA studies using the monoclonal antibody reveals
      considerable antigenic diversity among H. pylori strains. Serotyping of
      clinically isolated H. pylori Seems to be useful in clarifying the etiological
      roles of this bacteria. In spite of studies by several investigators, serotyping
      of H. pylori has not been established yet. Our studies suggest that H. pylori
      need to be further subdivided serologically.

PMID- 7506799
TI  - [Digestion of human gastric mucous by extracellular Helicobacter pylori enzyme].
AB  - Helicobacter pylori (Hp) is a causative pathogen of chronic gastritis and
      strongly associated with recurrence of duodenal ulcers, but the mechanism is not
      known. We studied the possible digestion of gastric mucus by Hp extracellular
      enzyme in human stomach. Hp was isolated from biopsy specimens taken from peptic
      ulcer patients or normal individuals and its extracellular enzyme was collected.
      Incubation of human gastric mucosa with Hp extracellular enzyme resulted in a
      significant decrease of PAS-positive staining, indicating digestion of gastric
      mucus. Analysis of protein profile of extracellular enzyme revealed no difference
      among Hp strains. Subsequent zymography showed 2 bands; 97 K and 20 K, indicating
      existence glycosyl-hydrase. These results suggest that Hp weakens gastric mucosal
      defense by digesting carbohydrates in the protective mucus layer.

PMID- 7506800
TI  - [Aphasia in stroke--pathogenesis, recovery, and treatment].

PMID- 7506801
TI  - [Syndromes of occlusions of cerebral arteries].

PMID- 7506803
TI  - [Clinical evaluation of a lung cancer-associated protein antigen, cytokeratin 19
      fragment: II. Radioimmunoassay and effect of aging and smoking over serum level
      of normal individuals].
AB  - Serum level of cytokeratin 19 fragment which is a tumor associated antigen of
      lung cancer was detected by the radioimmunometric assay. Effect of smoking and of
      aging on serum reference value was analyzed over 331 normal individuals. Serum
      cytokeratin 19 fragment level of smokers, mean 0.89ng/ml, was higher than that of
      non-smokers, mean 0.70ng/ml although there was no statistical meaning over the
      difference. And there was tendency to increase of cytokeratin 19 fragment level
      with aging. Mean + 2SD of cytokeratin 19 fragment of normal was 2.17ng/ml.
      Clinico-epidemiological specificity of cytokeratin 19 fragment on normal
      individuals was discussed.

PMID- 7506804
TI  - [A case of alpha-fetoprotein producing sigmoid colon cancer--a summary of 21
      cases in Japan].

PMID- 7506802
TI  - Acute myeloid leukemia possibly producing thrombopoietic factor(s).
AB  - A 75-year-old man developed a cluster of differentiation (CD)4-positive but human
      T-cell lymphotropic virus type I (HTLV-I)-negative T lymphoid neoplasm with
      overwhelming cutaneous involvement and mild thrombocytosis. Twelve courses
      tetrahydropyranyl adriamycin, cyclophosphamide, vincristine and prednisone (THP
      COP) combination chemotherapy led him to complete remission. After four months of
      complete remission, however, atypical immature cells (blasts) appeared in
      peripheral blood and bone marrow. Surface marker analysis revealed the blasts to
      be CD2-, CD3-, CD4-, CD5-, CD7+, CD8-, CD10, CD13 +/-, CD19-, CD20-, CD25-, CD33+
      and human leukocyte antigen-DR (HLA-DR+). Staining for myeloperoxidase,
      esterases, PAS and platelet peroxidase were all negative. The patient was
      diagnosed as having both CD7 and CD33 positive acute myeloid leukemia (AML). The
      relation between the T cell lymphoid neoplasm and AML was not clear.
      Thrombocytosis became more marked after acute leukemia occurred and the platelet
      count varied in parallel with the blast cell count in peripheral blood. When the
      leukemic cell count was high, thrombopoietic activity could be detected in the
      serum. In addition, conditioned medium obtained from primarily-cultured blasts
      had detectable thrombopoietic activity, which implied the blasts directly to
      produce a thrombopoietic factor(s). Analysis of the serum concentration for
      cytokines with associated thrombopoietic activity indicated that the blasts
      possibly produced a thrombopoietic factor(s) distinct from interleukin (IL)6,
      IL3, leukemia inhibitory factor (LIF), erythropoietin and granulocyte macrophage
      colony stimulating factor. To our knowledge, this is the first reported case of
      an acute myeloid leukemia with marked thrombopoiesis (more than 2000 x
      10(3)/microliter of maximum platelet count in peripheral blood.

PMID- 7506805
TI  - Pharmacological profile of KSG-504, a new cholecystokinin-A-receptor antagonist.
AB  - Pharmacological effects of KSG-504, a newly synthetized compound, on the response
      induced by exogenous CCK-8 were investigated. KSG-504 inhibited 125I-CCK-8
      binding to both rat pancreas and cerebral cortex with IC50 values of 2.0 x 10(-7)
      M and 8.0 x 10(-5) M, respectively. The selectivity ratio of KSG-504 for
      pancreatic CCK receptor (CCK-A) was estimated as 400. In the isolated pancreatic
      acini of rats, KSG-504 caused a parallel rightward shift of the concentration
      response curve for CCK-8-stimulated amylase release with no change in its maximal
      response, indicating a competitive antagonism of the drug for the CCK-A receptor
      (Schild plot analysis; slope = 0.927, pA2 = 6.9). In addition, KSG-504 produced a
      significant inhibition of CCK-8-induced pancreatic amylase secretion when
      administered intravenously or intraduodenally to rats (ED50: 52 micrograms/kg/min
      by the i.v. route and 12.1 mg/kg by the i.d. route). KSG-504 had equipotent
      inhibitory effects on both CCK-8-stimulated pancreatic secretion and gallbladder
      contraction in dogs with ED50 values of 0.98 and 0.84 mg/kg, respectively. KSG
      504 also inhibited the CCK-8-induced contraction of isolated guinea pig ileum in
      a concentration-dependent manner (IC50 = 3.0 x 10(-6) M). These results
      demonstrate that KSG-504 is a competitive and selective CCK-A-receptor antagonist
      that is effective in vivo after oral administration.

PMID- 7506806
TI  - The language of labour: an examination of the discourses of childbirth.
AB  - Language is a central component in our understanding of the social world. Not
      only is it our main form of interpersonal communication; it also constructs and
      reflects the wider social reality we all experience. Through examination of the
      language and terminology of childbirth different social meanings of language can
      be discovered. It is suggested that attention to the language reveals this
      diversity and increases our understanding of this area of social life and would
      be a fruitful area for research.

PMID- 7506808
TI  - Enhanced secretion of endothelin by endothelial cells in response to hemoglobin.
AB  - Confluent cultures of bovine aortic endothelium in serum-free medium were exposed
      to increasing concentrations (10(-6)-10(-4) M) of freshly prepared erythrocyte
      lysates (primarily hemoglobin). Hemoglobin increased endothelin-1 secretion into
      the medium in a dose-dependent manner after 24 hours. The enhanced secretion of
      endothelin-1 in response to hemoglobin was sustained for 72 hours, suggesting
      active production and secretion of endothelin-1 rather than release from
      intracellular pools. Secreted endothelin-1 in the medium was characterized by
      high-performance liquid chromatography coupled with radioimmunoassay. Endothelin
      1, a potent and long-lasting vasoconstrictor, may be one of the causative factors
      of cerebral vasospasm after subarachnoid hemorrhage. Oxyhemoglobin, derived from
      periarterial clot, may play an important role in the secretion of endothelin-1 in
      cerebral vasospasm.

PMID- 7506809
TI  - Effects of irradiation on cytokine production in glioma cell lines.
AB  - The effects of irradiation on cytokine production in glioma cell lines, NP1, NP2
      and NP3, were studied. Culture supernatants were collected after 6, 24, 48 or 72
      hours and the concentrations of interleukin (IL)-6 and IL-8 measured by enzyme
      linked immunosorbent assay. Spontaneous and IL-1 beta-stimulated productions were
      analyzed. Some cells were given a single dose of Lineac irradiation (10 or 20
      Gy). Production of IL-6 (with or without IL-1 beta stimulation) increased
      gradually to a maximum after 72 hours, more in the 20 Gy-irradiated cells than 10
      Gy cells (p < 0.01). Production of IL-8 increased gradually to a maximum after 48
      or 72 hours. Spontaneous production of IL-8 increased more in 20 Gy-irradiated
      cells than 10 Gy cells after 6 and 24 hours (p < 0.01), but increased more in 10
      Gy cells than 20 Gy cells after 48 and 72 hours (p < 0.01). The production of IL
      8 stimulated by IL-1 beta increased more in 10 Gy cells than 20 Gy cells 24 hours
      later (p < 0.01). IL-6 and IL-8 production differed in the response to
      irradiation. Our data suggest that bidirectional communication between the immune
      system and glioma cells changes after radiotherapy.

PMID- 7506807
TI  - A Fos-Jun element in the first intron of an alpha 2u-globulin gene.
AB  - The hepatic expression of the alpha-2u-globulin gene family is controlled by a
      variety of hormones including steroids, growth hormone and insulin. The
      mechanisms by which these hormones affect alpha 2u-globulin expression are only
      partially understood. Recently we isolated and characterized clone RAP 01, an
      alpha 2u-globulin gene expressed in the liver. In preliminary experiments we
      noted that partial hepatectomy, a procedure which results in a sharp rise in the
      level of the oncoproteins c-Fos and c-Jun, also causes a transient induction of
      the messenger RNA corresponding to clone RAP 01. Using the DNAseI footprinting
      technique we were able to show that this clone contains a TPA (phorbol 12
      myristate 13-acetate)-responsive element (TRE) in its first intron. This element
      (denoted as element X) is identical to the consensus AP-1 binding site (TGACTCAG)
      and is protected by rat liver nuclear extracts as well as by purified c-Jun. Gel
      retardation experiments show that an oligonucleotide containing the TRE consensus
      sequence competes for binding of liver nuclear proteins to element X and that
      antibodies directed against the M2 peptide of the mouse Fos protein or the PEP-2
      peptide of Jun prevent the formation of specific complexes with the same element.
      Moreover, element X functions as a TRE in transfected BWTG3 hepatoma cells
      treated with TPA. Co-transfection with fos and jun expression vectors mimics the
      effects of TPA suggesting that AP-1 is in fact the mediator of the observed
      response. It is concluded that the first intron of RAP 01 contains a functional
      Fos-Jun element.

PMID- 7506810
TI  - Effects of irradiation on the expression of the adhesion molecules (NCAM, ICAM-1)
      by glioma cell lines.
AB  - The expression of the intercellular adhesion molecule-1 (ICAM-1) and neural cell
      adhesion molecule (NCAM) by glioma cell lines was investigated. The effects of
      interferon (IFN)-gamma or irradiation on the expression was also assessed. Two
      glioma cell lines showed more than 75% NCAM-positive cells. After treatment with
      IFN-gamma or irradiation, another three cell lines were induced to show more than
      50% positive cells. Three glioma cell lines showed more than 50% ICAM-1-positive
      cells. After treatment with IFN-gamma, another two cell lines were induced to
      show more than 50% positive cells. After treatment with irradiation, one more
      cell line was induced to show more than 50% positive cells. ICAM-1 and NCAM
      expression by glioma cell lines is susceptible to modulation by IFN-gamma or
      irradiation.

PMID- 7506811
TI  - Hemodynamic study on flow patterns in the carotid bifurcation before and after
      carotid endarterectomy using cine magnetic resonance imaging.
AB  - Blood flow in the cervical carotid bifurcation was investigated by cine magnetic
      resonance imaging. In patients without stenosis, a low-intensity stream was
      demonstrated from the beginning of the carotid bulb, which was more distinct in
      the systolic phase. In patients with stenotic carotid bifurcations, the low
      intensity flow was also present but was more prominent than in the non-stenotic
      bifurcation. This low-intensity stream may be due to the change from steady to
      turbulent flow due to the geometric characteristics of the carotid bifurcation or
      atheromatous plaque, similar to the flow separation phenomenon in fluid dynamics
      because of the coincidence of location and flow pattern. After carotid
      endarterectomy, turbulent flow was seen at the proximal and distal ends of the
      endarterectomy. Close follow-up and administration of antiplatelet agents are
      necessary to prevent restenosis due to mural thrombosis induced by such turbulent
      flow.

PMID- 7506812
TI  - Magnetic resonance angiography of arteriovenous malformation in the brainstem.
AB  - The magnetic resonance (MR) angiography appearance of arteriovenous malformation
      (AVM) in the tegmentum and pons is described. The interpeduncular perforating
      branches of the posterior cerebral artery and median pontine branches of the
      basilar artery were seen more clearly by MR angiography than by conventional
      angiography. MR angiography was very useful for the follow-up of AVM after
      stereotactic radiosurgery.

PMID- 7506813
TI  - Magnetic resonance angiography of arteriovenous malformation in the thalamus.
AB  - A comparative study of magnetic resonance angiography and conventional
      angiography of arteriovenous malformation in the thalamus showed that both
      methods clearly visualized the feeding arteries: perforating branches of the
      posterior cerebral artery, posterior choroidal artery and lenticulostriate
      artery. Draining veins such as the internal cerebral vein were also demonstrated
      well.

PMID- 7506814
TI  - Vertebral artery dissecting aneurysm rebleeding after proximal occlusion--case
      report.
AB  - A 38-year-old male presented with vertebral artery dissecting aneurysm
      manifesting as subarachnoid hemorrhage. An attempt at trapping the aneurysm
      failed, so the vertebral artery could only be clipped proximally. Rebleeding
      occurred, resulting in death, probably due to excessive length of the dissection
      requiring thrombosis and/or retrograde dissection due to back pressure from the
      contralateral vertebral artery.

PMID- 7506815
TI  - Bilateral vertebral artery occlusion secondary to atlantoaxial dislocation with
      os odontoideum: implication for prophylactic cervical stabilization by fusion-
      case report.
AB  - A 27-year-old male presented with an unusual atlantoaxial dislocation associated
      with os odontoideum, after suffering sudden onset of significant neurological
      deterioration. Angiography demonstrated simultaneous occlusion of the bilateral
      vertebral arteries assumed responsible for the devastating neurological deficits.
      He initially underwent cervical immobilization with a Crutchfield tong for 2
      months and subsequent posterior fusion using an iliac bone graft and wires. The
      neurological symptoms gradually subsided, and 5 years later good healing of the
      bone graft without instability and ample subarachnoid space around the spinal
      cord were radiologically confirmed. Early prophylactic stabilization of
      atlantoaxial dislocation due to os odontoideum is recommended to prevent a poor
      outcome. Careful angiographic evaluation of the vertebrobasilar circulation is
      important for management of patients with os odontoideum.

PMID- 7506816
TI  - Use of STA-MCA anastomosis for clipping of giant middle cerebral artery aneurysm-
      case report.
AB  - A 50-year-old female developed subarachnoid hemorrhage due to rupture of a giant
      aneurysm in the left middle cerebral artery (MCA). One month later, direct
      surgery was performed on the aneurysm. The superficial temporal artery was
      anastomosed to the cortical artery of the parietal MCA segment. The MCA was
      exposed and trapped for 40 minutes during barbiturate infusion, with
      electroencephalographic and somatosensory evoked potential monitoring. During MCA
      trapping, the aneurysm was collapsed by dome puncture and obliterated by neck
      clipping. After surgery, she had only mild amnestic aphasia and an infarct in the
      medial temporal lobe demonstrated by computed tomography. However, cerebral
      angiography disclosed complete occlusion of the MCA by the displaced aneurysm
      clip, and perfusion of the distal MCA segments through the anastomosis. The
      initial bypass procedure prevented a disastrous outcome in this patient and is
      recommended for direct surgery on MCA aneurysms.

PMID- 7506817
TI  - Basal ganglia germinoma with crossed cerebellar diaschisis--case report.
AB  - An 8-year-old boy presented with a germinoma of the right basal ganglia
      manifesting as gradual onset of mild left hemiparesis. Computed tomography (CT)
      and magnetic resonance imaging disclosed a mass lesion in the right basal ganglia
      with mild right cerebral hemiatrophy. Single photon emission CT revealed
      decreased cerebral blood flow in both the right cerebral and left cerebellar
      hemispheres, or crossed cerebellar diaschisis. The histology of a specimen from a
      stereotactic needle biopsy was compatible with two-cell pattern germinoma. After
      irradiation and chemotherapy, the mass lesion disappeared completely. The
      clinical symptoms and crossed cerebellar diaschisis gradually improved.

PMID- 7506818
TI  - Lipocortin 1 mediates an early inhibitory action of glucocorticoids on the
      secretion of ACTH by the rat anterior pituitary gland in vitro.
AB  - Lipocortin 1 (LC1), a mediator of anti-inflammatory steroid action in some
      peripheral tissues, may contribute to the acute inhibitory effects of these
      steroids on hypothalamo-pituitary-adrenal (HPA) function. Accordingly, in the
      present study we have used an in vitro model to examine the potential role of
      this protein in the regulation of the release of corticotrophin (ACTH) from the
      anterior pituitary gland. Hypothalamic extracts (0.05-0.4 HE/ml), the 41 amino
      acid corticotrophin-releasing factor (CRF-41, 1-100 nM), the adenyl cyclase
      stimulator, forskolin (0.1 microM-10 mM), and the L-Ca2+ channel opener, BAY
      K8644 (0.01-10 mM), all caused concentration-dependent increases in the release
      in vitro of immunoreactive (ir)-ACTH from segments of rat anterior pituitary
      tissue. The secretory responses to submaximal concentrations of these
      secretagogues were overcome by preincubation of the tissue with dexamethasone
      (0.1 and 1 microM). LC1 was readily detectable by Western blotting in protein
      extracts of freshly excised pituitary tissue; a small proportion of the protein
      was found to be attached to the outer surface of the cell membranes where it was
      retained by a Ca(2+)-dependent mechanism. Exposure to dexamethasone (0.1 microM)
      in vitro did not affect the total LC1 content of the pituitary tissue but, over a
      2-hour period, it caused a progressive two- to fivefold increase in the amount of
      LC1 attached to the outer surface of the cell; this response developed in
      parallel with the inhibitory effects of the steroid on ir-ACTH release. Both the
      dexamethasone-induced 'externalization' of LC1 by the pituitary tissue and the
      concomitant steroid-induced inhibition of peptide release were blocked by
      cycloheximide (1.0 microgram/ml) but not by actinomycin D (0.5 microgram/ml). A
      stable N-terminal lipocortin 1 fragment, LC1(1-188) (10 pg-10 ng/ml), attenuated
      (p < 0.01) the release of ir-ACTH evoked by HE (0.1 HE/ml), CRF-41 (1 nM),
      forskolin (1 mM) and BAY K8644 (1 nM). Conversely, inclusion of the anti-LC1
      antibody in the medium substantially overcame the inhibitory effects of
      dexamethasone (0.1 microM) on the release of ir-ACTH evoked by the secretagogues
      whilst a control isotype matched antibody was without effect. The results suggest
      that LC1 plays a key role in effecting the acute inhibitory actions of
      glucocorticoids on the secretion of ir-ACTH by the rat anterior pituitary gland.

PMID- 7506819
TI  - Effect of hypersomatostatinemia on growth hormone secretion in cystic fibrosis
      patients with diabetes.
AB  - We have recently shown that hypersomatostatinemia is a feature of cystic fibrosis
      (CF) when these patients have CF-associated pancreatogenic diabetes mellitus
      (CFDM). To address the possibility that patients with CFDM might have suppressed
      pituitary growth hormone (GH) release as a result of increased plasma
      somatostatin, GH secretion in 8 CFDM patients and 8 normal male controls was
      studied using a standard arginine infusion stimulus. Concentrations of the GH
      dependent peptides, insulin-like growth factor I (IGF-I) and insulin-like growth
      factor binding protein 3 (IGFBP-3) were also measured. We found that mean GH
      concentrations in the CFDM group were significantly increased (p < 0.05) rather
      than decreased at the 30-min (12.3 +/- 3.6 vs. 3.8 +/- 1.9 ng/ml), 45-min (15.4
      +/- 2.9 vs. 6.1 +/- 2.3 ng/ml) and 60-min (13.2 +/- 2.3 vs. 6.2 +/- 2.2 ng/ml)
      time points of study. Mean GH area under the curve (633 +/- 128 vs. 249 +/- 107
      ng/ml) was also significantly greater (p < 0.05) in the CFDM group. Despite
      higher GH levels in the CFDM patients, their IGF-I and IGFBP-3 concentrations
      were low. We conclude that plasma somatostatin elevations in the CFDM group are
      not of sufficient magnitude to suppress pituitary GH release. Decreased levels of
      growth mediating peptides in the relatively malnourished CF subjects suggest a
      pattern of malnutrition-induced GH resistance which may contribute to poor weight
      and height gain.

PMID- 7506820
TI  - Altered expression of nerve growth factor in the skin of transgenic mice leads to
      changes in response to mechanical stimuli.
AB  - It has recently become clear that the neurotrophic factor, nerve growth factor,
      interacts specifically with nociceptive sensory neurons during development and
      maturity. Indeed, it may serve as a critical link between inflammation and the
      hyperalgesia that ensues in adult animals. Nerve growth factor is normally
      expressed in limiting amounts in target tissues of sensory and postganglionic
      sympathetic neurons. In the present study we have altered the basal level of
      nerve growth factor expression in the skin by producing transgenic mice that
      express a fusion gene construct containing either a sense or antisense nerve
      growth factor complementary DNA linked to the K14 keratin promoter. The K14-nerve
      growth factor transgene (sense or antisense) is abundantly expressed in skin from
      approximately embryonic day 15 and is then constitutively expressed throughout
      the life of the animal. In light of the fact that systemic administration of
      nerve growth factor to neonatal or adult rats leads to hyperalgesia, we have
      asked whether mice expressing the sense K14-nerve growth factor transgene exhibit
      similar sensory abnormalities and whether mice expressing the antisense nerve
      growth factor complementary DNA were hypoalgesic. Here we show that mice over
      expressing nerve growth factor in skin display a profound hyperalgesia to noxious
      mechanical stimulation. Additionally, K14-nerve growth factor antisense mice
      displayed a profound hypoalgesia to the same stimuli.

PMID- 7506822
TI  - Use of exfoliative cytology in the diagnosis of oral hairy leukoplakia.
AB  - The possibility of diagnosing oral hairy leukoplakia by means of exfoliative
      cytology and the Papanicolaou stain was investigated. Exfoliative cytology and
      punch biopsy specimens were obtained from 10 lesions that demonstrated clinical
      features of hairy leukoplakia. All biopsy specimens demonstrated the
      characteristic histopathologic features of hairy leukoplakia whereas all
      Papanicolaou-stained cytologic smears demonstrated condensation and margination
      of the nuclear chromatin (nuclear beading). All biopsy specimens and cytologic
      smears displayed positive Epstein-Barr virus deoxyribonucleic acid in situ
      hybridization. We conclude that routine exfoliative cytology may be a reliable,
      noninvasive, and inexpensive technique for the diagnosis of hairy leukoplakia.

PMID- 7506821
TI  - Effects of acidic fibroblast growth factor on cholinergic neurons of nucleus
      basalis magnocellularis and in a spatial memory task following cortical
      devascularization.
AB  - The ability of acidic fibroblast growth factor to elicit a trophic response in
      the nervous system of the rat was tested in vitro and in vivo. Treatment of
      cultured septal cells with acidic fibroblast growth factor resulted in an
      elongation of glial processes as assessed by immunostaining for glial fibrillary
      acidic protein. Increased choline acetyltransferase was also observed. The
      responses to acidic fibroblast growth factor in vivo were studied in rats trained
      in a spatial memory task, using the Morris water maze. Randomly selected animals
      were subjected to unilateral cortical devascularization. This lesion results in
      partial unilateral infarction of the neocortex, and in retrograde degeneration of
      the nucleus basalis magnocellularis. Animals were tested post-lesion for memory
      retention and were then killed for morphological studies. Intracerebroventricular
      administration of acidic fibroblast growth factor (0.6 microgram/h for seven days
      starting at surgery) prevented the lesion-induced impairment in this test, and
      reduced the nucleus basalis magnocellularis cholinergic degeneration, as assessed
      by morphometric choline acetyltransferase-like immunoreactivity and
      radioenzymatic assay for choline acetyltransferase activity. The preservation of
      the phenotype of injured cholinergic neurons of the nucleus basalis
      magnocellularis by acidic fibroblast growth factor was indicated by the
      maintenance of the cross-sectional area of cell bodies and mean length of
      neuritic processes one month after surgery. The effect of acidic fibroblast
      growth factor in non-cholinergic cells remains to be investigated. It is
      suggested that acidic fibroblast growth factor may alleviate the lesion-induced
      deficit in the memory retention task by preventing disruption of functional
      connections between nucleus basalis magnocellularis and intact cortical
      areas.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506823
TI  - Leiomyosarcoma metastatic to the oral region. Report of three cases.
AB  - Leiomyosarcoma, a malignant lesion of smooth muscle origin, is rare in the oral
      region. Metastatic leiomyosarcoma may originate from several potential primary
      sites, and the lung is the most common target tissue for metastatic deposits.
      This article describes three cases of leiomyosarcoma that were metastatic to the
      oral cavity and discusses the clinical and histopathologic differential
      diagnosis.

PMID- 7506824
TI  - Transcriptional rates of granulocyte-macrophage colony-stimulating factor,
      granulocyte colony-stimulating factor, interleukin-3, and macrophage colony
      stimulating factor genes in activated cord versus adult mononuclear cells:
      alteration in cytokine expression may be secondary to posttranscriptional
      instability.
AB  - We have previously demonstrated that protein production and mRNA expression of
      granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony
      stimulating factor (G-CSF), and IL-3 are decreased in activated mononuclear cells
      (MNC) from human umbilical cord compared with adult peripheral blood. Reduced
      production of these colony-stimulating factors (CSF) during states of increased
      demand, as occurs during overwhelming bacterial infection, may play a role in the
      pathogenesis of neutropenia and thrombocytopenia in the newborn. To determine
      whether the reduced mRNA expression and CSF production from activated cord MNC is
      secondary to the decreased transcriptional activity of the corresponding genes,
      we determined the transcriptional rate of GM-CSF, G-CSF, IL-3, and M-CSF by
      nuclear run-on assays. Cord and adult MNC were isolated by Ficoll-Hypaque density
      centrifugation. A total of 10(8) MNC from cord and adult blood were stimulated as
      follows: GM-CSF and G-CSF [32 nmol/L phorbol-12-myristate-6-acetate (20
      micrograms/L) + 2 mg/L phytohemagglutinin for 6 h]; IL-3 [32 nmol/L phorbol-12
      myristate-6-acetate (20 micrograms/L) + 0.5 mumol/L A 23187 for 6 h]; and
      macrophage CSF (2 micrograms/L recombinant human GM-CSF for 24 h). The nuclei
      from unstimulated and stimulated cells were isolated and labeled with 32P-uridine
      triphosphate. Newly elongated 32P-labeled RNA transcripts were hybridized to slot
      blots of CSF DNA. To minimize cross hybridization artifacts, short fragments (0.5
      1.0 kb) of cDNA were used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506825
TI  - Persistently altered T cell immunity in high school students with the congenital
      rubella syndrome and profound hearing loss.
AB  - Because there are frequent progressive and autoimmune complications in children
      born with the congenital rubella syndrome, we evaluated immunoregulation in eight
      profoundly deaf adolescents with congenital rubella syndrome who lived in a state
      school. Serum antiviral antibodies, expressions of peripheral lymphocyte epitopes
      and serum soluble interleukin 2 receptor (IL-2R) content were compared with those
      of 16 classmates with profound hearing loss of unknown cause and of 24 age
      matched, hearing students from this area. Both deaf groups showed activated but
      impaired T lymphocyte function compared with normals. Rubella virus alteration of
      T cell function was suggested in congenital rubella syndrome students by elevated
      numbers of both CD4+ helper and CD25+ IL-2R cells with unusually low released
      soluble IL-2R content. In contrast in deaf classmates elevated CD25+ and CD16+
      natural killer cell groups and soluble IL-2R content with low numbers of CD4+
      helper cells and CD4+ populations were of unknown etiology. Defective
      immunoregulation of the congenitally deaf to pathogens inherent in their
      environment may lead to autoimmune and other complications.

PMID- 7506826
TI  - Comparison of the Vineland Social Maturity Scale, the Vineland Adaptive Behavior
      Scales--survey form, and the Bayley Scales of Infant Development with infants
      evaluated for developmental delay.
AB  - The Vineland Adaptive Behavior Scales is an extensive revision of the Vineland
      Social Maturity Scale; however, research comparing the two scales with different
      populations and measures of intelligence is limited. The Vineland Adaptive
      Behavior Scales--Survey Form, the Vineland Social Maturity Scale, and the mental
      scale of the Bayley Scales of Infant Development were administered to 44 infants
      referred for evaluation of developmental delay. The differences between means
      were compared and shared variance examined. The Vineland Adaptive Behavior Scales
      -Survey Form scores were significantly higher than those of the Vineland Social
      Maturity Scale and the Bayley Mental Development Index. No significant
      differences were found between the means of the Vineland Social Maturity Scale
      and the Bayley Scales of Infant Development--Mental Development Index.
      Correlations were .59 between the Bayley Index and scores on the Vineland--Survey
      Form and .72 between the Bayley Index and the Vineland Social Maturity Scale.
      Between versions of the Vineland scale r = .39. Implications for diagnosis and
      educational classification are discussed.

PMID- 7506828
TI  - Structure specific ds/ss-RNase activity in the extreme halophile Halobacterium
      salinarium.
AB  - A ds/ss-RNA processing activity involved in antisense-RNA mediated gene
      regulation in the extremely halophilic archaebacterium Halobacterium salinarium
      was investigated in vivo. H.salinarium cells were transformed with DNA encoding
      an RNA species complementary to a part of the major lytic transcript, termed T4,
      of the H.salinarium phage phi H. The transformants transcribing this construct,
      when infected by phage were able to process T4 in a similar way to the processing
      of the lytic transcript denoted T1, in the natural sense-antisense system.
      Processing of T4 was not observed under normal phage growth on wild-type cells.
      Thus the antisense-RNA mediated processing activity earlier reported is dependent
      on the presence of an RNA duplex and is not sequence specific.

PMID- 7506827
TI  - Stability of triple helices containing RNA and DNA strands: experimental and
      molecular modeling studies.
AB  - UV-absorption spectrophotometry and molecular modeling have been used to study
      the influence of the chemical nature of sugars (ribose or deoxyribose) on triple
      helix stability. For the Pyrimidine.purine* Pyrimidine motif, all eight
      combinations were tested with each of the three strands composed of either DNA or
      RNA. The chemical nature of sugars has a dramatic influence on triple helix
      stability. For each double helix composition, a more stable triple helix was
      formed when the third strand was RNA rather than DNA. No stable triple helix was
      detected when the polypurine sequence was made of RNA with a third strand made of
      DNA. Energy minimization studies using the JUMNA program suggested that
      interactions between the 2'-hydroxyl group of the third strand and the phosphates
      of the polypurine strand play an important role in determining the relative
      stabilities of triple-helical structures in which the polypyrimidine third strand
      is oriented parallel to the polypurine sequence. These interactions are not
      allowed when the third strand adopts an antiparallel orientation with respect to
      the target polypurine sequence, as observed when the third strand contains G and
      A or G and T/U. We show by footprinting and gel retardation experiments that an
      oligoribonucleotide containing G and A or G and U fails to bind double helical
      DNA, while the corresponding DNA oligomers form stable triple-helical complexes.

PMID- 7506829
TI  - Activity of hammerhead ribozymes containing non-nucleotidic linkers.
AB  - Hammerhead ribozymes were synthesized in which the tetranucleotide loop II was
      replaced by non-nucleotidic linkers of 7, 13, 17 and 19 atoms length. Ribozymes
      with 17 and 19 atom linkers, in combination with a 4 base pair stem II, had
      catalytic efficiencies which were 2 fold increased to that of the parent ribozyme
      with a tetranucleotide loop. Ribozymes with these linkers, but in combination
      with a 2 base pair stem II, showed a 2 fold decrease in catalytic efficiency when
      compared to the parent ribozyme. Prolonged preincubation in the presence of MgCl2
      was required for hexaethylene glycol linker-modified ribozymes to obtain maximum
      activity and reproducible kinetic data.

PMID- 7506830
TI  - Enhancement of the cleavage rates of DNA-armed hammerhead ribozymes by various
      divalent metal ions.
AB  - In order to characterize structure-function relationships, the kinetic behavior
      of chimeric RNA/DNA ribozyme was compared with that of all RNA ribozyme.
      Determined kcat values were proven to represent the chemical-cleavage step and
      not the product-dissociation step. In agreement with the finding by Dahm and
      Uhlenbeck [Biochemistry 30, 9464-9469 (1991)], various metal ions, including Co2+
      and Ca2+ with the ionic radius of 0.65 and 1.0 A, respectively, could support
      hammerhead cleavage for both types of ribozyme. Measurements of kinetic
      parameters in the presence of various divalent metal ions revealed that DNA arms
      always enhanced kcat values. Chemical-probing data using dimethylsulfate
      indicated that the catalytic-loop structures of all-RNA and chimeric ribozymes
      were nearly identical with the exception of enhanced termination of primer
      extension reactions at C3 in the case of the chimeric ribozyme. These
      observations and others demonstrate that DNA substitution in non-catalytic-loop
      regions increases chemical-cleavage activity, possibly with an accompanying very
      subtle change in the structure.

PMID- 7506831
TI  - Protease inhibitors suppress in vitro growth of human small cell lung cancer.
AB  - The effect of the protease inhibitors Bowman Birk inhibitor (BBI) and aprotinin
      on the in vitro clonal growth of two human small cell lung cancer (SCLC) cell
      lines was investigated. In addition, the effect of BBI on the growth factor
      processing of proGRP by SCLC cells and on mRNA levels for prohormone convertase 1
      and 2 (PC1 and PC2) in SCLC cells was examined. The protease inhibitors BBI and
      aprotinin significantly decreased growth in both SCLC cell lines studied. In NCI
      H345 cells, BBI appears to inhibit the processing of proGRP to GRP, as indicated
      by Western blot analysis. NCI-H345 cells, when treated with BBI (100
      micrograms/ml), also showed highly significant decreases of mRNA for PC1 and PC2
      of about 50%. These data suggest that proteases serve an important role in the
      growth regulation of SCLC and that inhibitors of these proteases may be potent
      suppressors of SCLC growth at the level of the gene.

PMID- 7506832
TI  - Galanin immunoreactivity in rat spinal lamina IX: emphasis on sexually dimorphic
      regions.
AB  - Fibers and puncta that contained galanin-like immunoreactivity (GAL-LI) were
      distributed within lamina IX in a heterogeneous fashion. In cervical spinal
      segments, GAL-LI was almost absent except for the phrenic nucleus, which received
      the most robust GAL-LI innervation in lamina IX. In high and mid-thoracic
      segments, GAL-LI was found in moderate amounts, but the number of GAL-LI fibers
      gradually diminished in a caudal fashion, so that in low thoracic segments GAL-LI
      was sparse. Throughout all thoracic segments, GAL-LI fibers surrounded some
      clusters of motoneurons, while other groups of motoneurons were devoid of GAL-LI
      fibers. In lumbar segments, three sexually dimorphic nuclei received sparse to
      moderate amounts of GAL-LI, while GAL-LI in the remainder of lumbar lamina IX was
      very sparse. In sacral spinal segments, GAL-LI was very sparse. These data
      indicate that fibers and puncta that contain GAL-LI preferentially surround
      motoneurons that innervate muscles associated with the axial skeleton, while
      motoneurons that innervate appendicular or tail-associated skeletal muscles only
      have an occasional GAL-LI fiber associated with them.

PMID- 7506833
TI  - Interactions of CD4 with MHC class II molecules, T cell receptors and p56lck.
AB  - CD4 and CD8 are members of the immunoglobulin supergene family of proteins, and
      function as co-receptors with the T cell receptor (TCR) in binding MHC class II
      or class I molecules, respectively. Within this multimeric complex, CD4 interacts
      with three distinct ligands. CD4 interacts through its D1 and D2 domains with MHC
      class II proteins, through its D3 and D4 domains with T cell receptors, and
      through its cytoplasmic tail with p56lck, a src-related, protein tyrosine kinase.
      Each of these interactions is important in the function of CD4 and will be
      discussed in turn.

PMID- 7506834
TI  - 4-Thiouridine incorporation into the RNA of monkey kidney cells (CV-1) triggers
      near-UV light long-term inhibition of DNA, RNA and protein synthesis.
AB  - Monkey kidney cells (CV-1) grown for 4 h in the presence of 0.1 mM 4-thiouridine
      (s4Urd) incorporate this photoactivable uridine analog in their RNA. A minor, 5
      8%, thiolated RNA fraction can be isolated from bulk RNA by affinity
      chromatography. This RNA fraction contains 1.5-2.5 s4Urd residues per 100
      nucleotides and exhibits a broad chain length distribution ranging from 700 to
      7000 nucleotides. It is essentially of nuclear origin and amounts to 30% of the
      RNA synthesized during exposure of cells to s4Urd. Under the same s4Urd labeling
      conditions, no thiolated pyrimidine residues have been detected in DNA.
      Irradiation with 365 nm light (45 kJ/m2) of the cells immediately after s4Urd
      exposure triggers long-term inhibition of DNA, RNA and protein synthesis
      accompanied by a linear decline (50% in 2 days) in the total cell mass of
      cultured cells. In contrast, exposure to s4Urd alone results in moderate but
      reversible inhibitory effects. The available data suggest that s4Urd-induced
      photolesions in newly synthesized RNA such as RNA-RNA cross-links as well as RNA
      protein bridges are directly involved in impairment of essential cellular
      functions.

PMID- 7506835
TI  - Adrenal carcinoma.
AB  - Adrenal cortical carcinoma is an uncommon but highly malignant tumor. Functioning
      tumors are detected earlier than nonfunctioning neoplasms such that patients with
      functioning tumors are younger and the tumors smaller than in patients with
      nonfunctioning tumors. Most tumors are quite large by presentation and are easily
      detected by imaging studies. CT is the primary imaging modality and can be used
      to stage most patients accurately. MR may be employed to clarify equivocal
      findings, especially the delineation of venous extension. Surgery is the only
      effective treatment, so precise tumor delineation is essential. Chemotherapy with
      ortho para DDD provides some palliation, but the prognosis remains poor.

PMID- 7506836
TI  - Benign prostatic hyperplasia: value of MR imaging for determining histologic
      type.
AB  - PURPOSE: To assess the value of magnetic resonance (MR) imaging for determining
      the histologic type of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS:
      Unenhanced T1- and T2-weighted images and gadolinium-enhanced T1-weighted images
      were obtained in the transverse plane at 1.5 T in 33 patients with BPH.
      Hyperphasia was classified as stromal or nonstromal. Nonstromal hyperplasia was
      diagnosed if (a) the nodules in the inner gland had heterogeneous high signal
      intensity on T2-weighted images and peripheral enhancement on gadolinium-enhanced
      images, (b) a surgical capsule was present, or (c) the inner gland volume to
      total volume ratio was greater than 0.75. RESULTS: A correct diagnosis was made
      with MR imaging in 23 of 24 patients with nonstromal hyperplasia and eight of
      nine with stromal hyperplasia (94% accuracy). In nonstromal hyperplasia, nodular
      lesions were seen in 20 patients and a surgical capsule was seen in 19. Eighteen
      patients had a transition zone ratio greater than 0.75. CONCLUSION: MR imaging
      appears to be useful for choosing the type of pharmacotherapy performed because
      accurate histologic assessment is possible.

PMID- 7506838
TI  - Effects of inhibition of nitric oxide synthase on systemic arterial pressure and
      renal vascular resistance in cats.
AB  - These studies were undertaken to examine the systemic and renal effects of the
      pharmacological inhibition of endothelium-derived nitric oxide (EDNO) in cats. In
      six healthy cats, the intravenous infusion of nitro-L-arginine at a dose of 100
      micrograms kg-1 bodyweight min-1 resulted in a marked increase (P < 0.001) in
      mean arterial pressure from the control value of 116.7 +/- 4.6 mmHg to 154.2 +/-
      6.8 mmHg and an increase (P < 0.05) in renal vascular resistance from the control
      value of 3.69 +/- 0.33 mmHg min ml-1 to 6.83 +/- 1.15 mmHg min ml-1. The increase
      in renal vascular resistance was generalised, with comparable increments in
      preglomerular and postglomerular vascular resistance. Mean values for glomerular
      capillary pressure (61.1 +/- 1.9 vs 61.9 +/- 1.6 mmHg), calculated from the sum
      of arterial colloid osmotic pressure plus proximal tubule stop-flow pressure, did
      not change in response to the infusion of nitro-L-arginine. However, there was a
      marked reduction in renal blood flow (29.4 +/- 3.1 to 16.9 +/- 2.3 ml min-1, P <
      0.01) and glomerular filtration rate (5.22 +/- 0.57 to 3.52 +/- 0.45 ml min-1, P
      < 0.01). These results provide evidence that EDNO plays an important role in the
      basal regulation of systemic arterial blood pressure and renal haemodynamics in
      cats.

PMID- 7506837
TI  - Acute phase protein response, food intake, liveweight change and lesions
      following intrathoracic injection of yeast in sheep.
AB  - Acute phase protein concentrations in blood, food intake and liveweight changes
      were compared in 10 sheep given intrathoracic injections of yeast and 10 control
      sheep over a period of 61 days. The yeast injections caused acute pleuritis and
      limited necrotising lung lesions which progressed to fibrous pleural adhesions
      and walled-off abscesses. The responses of ceruloplasmin, fibrinogen and
      haptoglobin were closely correlated (r = 0.87 to 0.91) in the yeast-injected
      sheep with peaks on days 5 or 7 after treatment (4, 4.6 and over 130 times
      control, respectively). Albumin concentration fell to a nadir of 89 per cent of
      control on day 12 after treatment. Depression of food intake was temporally
      related to the 'positive' acute phase protein responses with a nadir on day 5
      after treatment (30 per cent of control). Liveweight showed a pronounced fall to
      five days after treatment and thereafter remained depressed relative to the
      controls for most of the experimental period. The data suggest that the
      'positive' acute phase proteins may be useful indicators of production losses due
      to inflammatory diseases in sheep.

PMID- 7506839
TI  - Analysis of gene selection in reassortant formation between canine rotavirus K9
      and human rotaviruses with different antigenic specificities.
AB  - A number of antigenic mosaic reassortants which have neutralization proteins VP4
      and VP7 derived from different parental strains were analysed in order to study
      gene selection in reassortant formation between animal and human rotaviruses
      (HRV). These reassortants were isolated from mixed infection of MA-104 cells with
      canine rotavirus strain K9 (subgroup I and G serotype 3) and HRV strains (with
      subgroup I or II antigen and G serotype 1-4, 9 or 12 antigen), through repeated
      selections with anti-VP4 and anti-VP7 neutralizing monoclonal antibodies directed
      specifically at HRV and K9, respectively. By serological and genomic analyses,
      all the isolated clones were found to be antigenic mosaic reassortants possessing
      VP4 of K9 and VP7 of HRV. In the reassortants between strain K9 and one of the
      six strains of subgroup II HRV, a single or a few genotypes with particular
      constellations of RNA segments were predominant, with only a few RNA segments
      including gene 4 (encoding VP4) being derived from K9. In contrast, in the
      reassortants between strain K9 and any one of the subgroup I HRV, more than nine
      different genotypes were identified and various RNA segments, except for segments
      8 and 10, were derived from K9. These findings indicated that the RNA segments of
      K9 might be reassorted more readily with those of subgroup I HRV than with those
      of subgroup II HRV, suggesting the possible existence of functional mechanisms
      which determine the extent of diversity of genome selection depending on the
      pairs of parent strains in the reassortant formation.

PMID- 7506840
TI  - [Anaphylaxis after dextran 40 infusion: report of a case and review of the
      literature].
AB  - Anaphylactic reactions to colloid volume substitutes, such as dextran, are rare,
      however, with their increasing utilization in clinical practice an increasing
      awareness of their potential antigenicity is required. This article reports a
      severe allergic reaction induced by infusion of dextran 40 during the beginning
      of a general anesthesia in a 59 year old patient who was going to be submitted to
      an operation for treatment of chagasic megacolon. The patient died from this
      complication after 28 days. A review of literature of this complication and a
      discussion about its physiopathological mechanism and prevention is presented.

PMID- 7506841
TI  - Safety of enoxaparin and dextran-70 in the prevention of venous thromboembolism
      in digestive surgery. A play-the-winner-designed study.
AB  - A total of 327 patients were included in a play-the-winner (PTW)-designed study
      comparing the safety of prophylaxis with enoxaparin and dextran-70 in patients
      undergoing digestive surgery. In a PTW-designed study the treatment of any next
      patient will depend on the outcome of the previous one. If successful, the next
      patient will receive the same treatment. Excessive bleeding, on the basis of
      specified criteria, severe adverse effects, or occurrence of clinically detected
      venous thromboembolism was classified as failure. The PTW design allocates most
      patients to the superior treatment. In this study 200 patients were given
      enoxaparin and 127 dextran-70. The success rate was 83% in the enoxaparin group
      and 74.8% in the dextran-70 group (p = 0.05). The survival analysis of 'Number of
      patients before change in treatment' shows a significant difference in favour of
      enoxaparin (p = 0.05). Enoxaparin seems to be superior to dextran-70 as a
      prophylaxis in digestive surgery. The PTW model is a suitable design in such
      studies.

PMID- 7506842
TI  - Important role of hepatitis C virus infection as a cause of chronic liver disease
      in Somalia.
AB  - In a case-control study, 62 Somali patients with chronic liver disease (CLD)
      including primary hepatocellular carcinoma (HCC) and the same number of age and
      sex matched controls were investigated for serological markers of hepatitis C
      virus (HCV) and hepatitis B virus (HBV) infections. Antibody to HCV (anti-HCV)
      was detected in 40.3% and 6.5% of cases and controls, respectively. The
      corresponding prevalences of hepatitis B surface antigen (HBsAg) were 37.1% and
      9.7%, respectively. Of the HBsAg-positive cases, 34.6% had antibodies to
      hepatitis D virus (anti-HD) compared with 14.3% among the HBsAg-positive
      controls. Anti-HCV was less prevalent in HBsAg-positive cases than among HBsAg
      negative patients (p < 0.001), indicating that these agents were independent
      causes of CLD/HCC. The odds ratios for patients with CLD/HCC associated with the
      presence of anti-HCV, anti-HD, HBsAg without anti-HD and anti-HCV, were found to
      be 9.8, 10.4, and 3.3, respectively. When the patients were divided into tumour
      and non-tumour cases, using the criteria of serum alpha-fetoprotein > 100 ng/ml
      and/or solid hepatic lesions detected by ultrasonography, they did not differ
      with regard to frequencies of HBsAg and/or anti-HCV, although they did differ
      when these markers were taken together (43/49 versus 5/13, respectively). The
      mean age of the tumour patients with anti-HCV alone was significantly higher than
      that of tumour patients with HBsAg as the sole marker, 61.7 versus 31.4 years (p
      < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506843
TI  - What are we? Where did we come from? Where are we going?

PMID- 7506846
TI  - Palliative radiotherapy in asymptomatic patients with locally advanced,
      unresectable, non-small cell lung cancer.
AB  - Between 1983 and 1990, 332 patients with non-small cell lung cancer (NSCLC) were
      referred to short-time, split-course palliative thoracic radiotherapy. The group
      consisted of patients with locally advanced (III degrees), unresectable cancer,
      not suitable for curative radiotherapy, asymptomatic or having only minimal
      symptoms related to intrathoracic tumor. The therapeutic plan involved two series
      of irradiation. Tumor dose delivered in each series was 20 Gy given in five daily
      fractions over five treatment days. There were four weeks interval between
      series. Of 332 patients initially qualified to thoracic radiotherapy only 170
      patients received the treatment; the other 162 patients were not irradiated
      because of treatment refusal or logistic problems concerning therapy. They made
      the control group of the study, receiving the best possible symptomatic care.
      Twelve-month survivals in the radiotherapy and control groups were 32.4% and
      9.3%, respectively; 24-month survivals 11.2% and 0%, respectively. Improvement of
      survival after palliative thoracic radiotherapy was observed only in patients
      with clinical stage IIIA and Karnofsky's performance status (KPS) > or = 70.

PMID- 7506844
TI  - The transfer RNA identity problem: a search for rules.
AB  - Correct recognition of transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases is
      central to the maintenance of translational fidelity. The hypothesis that
      synthetases recognize anticodon nucleotides was proposed in 1964 and had
      considerable experimental support by the mid-1970s. Nevertheless, the idea was
      not widely accepted until relatively recently in part because the methodologies
      initially available for examining tRNA recognition proved hampering for
      adequately testing alternative hypotheses. Implementation of new technologies has
      led to a reasonably complete picture of how tRNAs are recognized. The anticodon
      is indeed important for 17 of the 20 Escherichia coli isoaccepting groups. For
      many of the isoaccepting groups, the acceptor stem or position 73 (or both) is
      important as well.

PMID- 7506845
TI  - Ventricular tachycardia in acute myocardial infarction: the role of
      hypophosphatemia.
AB  - The relationship between serum concentration of certain electrolytes and the
      pathogenesis of ventricular arrhythmia in myocardial infarction has been the
      subject of frequent review. The role of hypophosphatemia in the pathogenesis of
      arrhythmia in patients with acute myocardial infarction has not been as well
      studied. In our study group of 325 consecutive patients admitted to the coronary
      care unit of a community hospital, 111 were confirmed to have had a myocardial
      infarction. Patients were continuously monitored for ventricular arrhythmia
      during the first 24 hours, and the electrocardiographic records were reviewed for
      documentation of arrhythmia. From an admission blood sample, measurement of
      electrolytes included serum phosphate, calcium, bicarbonate, potassium, and
      magnesium. Associations between ventricular tachycardia and serum electrolyte
      abnormalities including magnesium, potassium, phosphate, calcium, and bicarbonate
      were studied. Low phosphate (less than 2.6 mg/dL) was a significant predictor of
      ventricular tachycardia in the myocardial infarction group. In the entire group
      of 325 patients prior to the confirmation of myocardial infarction, both low
      bicarbonate and low phosphate were significant predictors of ventricular
      tachycardia during the first 24 hours of hospitalization. Although management of
      acidosis is considered early in the hospital course, phosphate replacement
      therapy is usually not as often considered. We recommend further study on the
      effectiveness of replacement therapy in hypophosphatemic patients with chest pain
      to reduce the risk of ventricular tachycardia.

PMID- 7506848
TI  - The Lady with the Lamp. Nightingale: the enduring symbol.

PMID- 7506847
TI  - Granulocyte colony-stimulating factor reverses septic shock-induced
      polymorphonuclear leukocyte dysfunction.
AB  - BACKGROUND: Polymorphonuclear leukocyte (PMN) function is dependent on normal Fcg
      receptor expression. Fibronectin and laminin are each capable of modulating the
      surface expression of CD32w (Fc gamma RII) and CD16 (Fc gamma RIII). Their
      ability to alter CD64 (Fc gamma RI) expression, however, was unclear; therefore
      the purpose of these studies was to define the role of CD64 (Fc gamma RI) in
      modulating PMN oxidative metabolism and degranulation for PMNs adherent to either
      fibronectin or laminin. METHODS: Experiments were performed in two phases;
      initially, PMNs isolated from normal volunteers and adherent to buffer,
      fibronectin, or laminin were studied. Subsequently, two groups of patients were
      evaluated; group 1 (n = 8) represents control patients undergoing major
      intraabdominal procedures. Group 2 (n = 12) represents patients in septic shock
      from defined sources of intraabdominal infection. Monomeric immunoglobulin G was
      used as a specific ligand for CD64 followed by measurements of superoxide anion,
      hypochlorous acid, and N-acetyl-beta-glucosaminidase production to measure
      oxidative metabolism and azurophilic granule degranulation. Six cytokines were
      then tested to determine their ability to restore biologically active CD64 on
      group 2 PMNs. RESULTS: Fibronectin or laminin increased CD64 on PMNs of normal
      volunteers and group 1 patients. CD64 signal transduction augmented superoxide
      anion, hypochlorous acid, and N-acetyl-beta-glucosaminidase production by PMNs of
      volunteers and group 1. Neither fibronectin nor laminin increased CD64 expression
      on group 2 PMNs. Granulocyte colony-stimulating factor restored both receptor
      number of CD64 and biologic activity of these receptors on the surface of group 2
      PMNs in the presence of fibronectin or laminin. CONCLUSIONS: Septic shock
      depresses CD64 expression on the PMN surface. Restoration of this receptor by
      granulocyte colony-stimulating factor not only augments receptor number but also
      improves oxidative metabolism and primary granule degranulation in the presence
      of either fibronectin or laminin.

PMID- 7506849
TI  - Two novel monoclonal antibodies reactive with different components of the rat
      thymic epithelium.
AB  - Two novel monoclonal antibodies (mAbs) (PT10B7 and PT13D11) have been raised
      against molecules of rat thymic epithelial cells (TEC). Streptavidin-biotin
      immunoperoxidase staining and double immunofluorescence using these mAbs and anti
      cytokeratin (CK) antibodies showed that PT10B7 and PT13D11 mAbs bound to
      different components of rat TEC. PT10B7 mAb reacted with cortical and a subset of
      medullary TEC, whereas PT13D11 mAb labeled subcapsular/perivascular and most
      medullary TEC, including TE-R 2.5 TEC line of medullary origin. Their staining
      patterns were different from those seen using mAbs to CK10, CK18 and CK19
      polypeptides and other anti-rat TEC mAbs produced so far. The differences in
      immunoreactivity of these two mAbs on rat thymus during ontogeny and on other
      epithelial cells of adult rats were also seen. Namely, PT13D11 stained ectoderm
      derived epithelia, whereas PT10B7 stained some cells of simple epithelia.
      Cumulatively, these results reveal a fine phenotypic heterogeneity within rat
      thymic epithelium.

PMID- 7506850
TI  - [PSA volume quotient: an additional parameter in diagnosis of locally confined
      prostate cancer].
AB  - The sensitivity and specificity of prostate-specific antigen density (PSAD), a
      quotient of serum PSA and prostate volume, in the detection of localized prostate
      cancer was analysed in a prospective study. A total of 235 patients were
      examined, 145 without prostate cancer and 90 patients before radical
      prostatectomy for localized prostate cancer. PSAD was determined by dividing the
      serum level of PSA by the volume of the entire prostate (estimated by transrectal
      ultrasound) and multiplying by 100. Using a PSAD of 15, the specificity achieved
      in our collective was the same as with an absolute PSA value of 4 ng/ml (88.9
      90%). On the other hand, with the PSAD of 15 we also found the same sensitivity
      as with an ab-solute PSA of 10 ng/ml (75.2-76.5%).

PMID- 7506851
TI  - [Gastrostomy instead of gastric intubation for stomach decompression after large
      urologic operations].
AB  - In 31 patients who had undergone extensive intraabdominal urological surgery, a
      gastrostomy was performed for gastric decompression instead of introduction of a
      nasogastric tube. There were no complications during the procedure. All patients
      tolerated the gastrostomy well. Two were fed through the gastrotomy. We conclude,
      that gastrostomy is a safe method of gastric decompression.

PMID- 7506852
TI  - Value of preoperative PSA in predicting pathologic stage of patients undergoing
      salvage prostatectomy.
AB  - OBJECTIVE: To evaluate the relationship of prostate-specific antigen (PSA) levels
      and pathologic stage in patients with prostate cancer treated with radiation
      therapy and undergoing salvage radical prostatectomy. METHOD: Retrospective
      analysis of preoperative PSA levels and final pathology in 24 men undergoing
      salvage prostatectomy following prior radiation therapy. RESULTS: Although
      preoperative PSA values were significantly higher in patients with positive
      surgical margins, preoperative PSA levels failed to predict the presence of
      absence of extracapsular extension, seminal vesicle involvement, or lymph node
      metastasis. CONCLUSION: Our results suggest that PSA is not a reliable method of
      accurately predicting the pathologic stage of patients who are candidates for
      salvage radical prostatectomy.

PMID- 7506853
TI  - Prospective evaluation of prostate-specific antigen density and systematic
      biopsies for early detection of prostatic carcinoma.
AB  - Significant controversies persist in regard to the need for systematic biopsies
      in patients with serum prostate-specific antigen (PSA) levels above 4 ng/mL
      (Hybritech assay), especially if they show no signs of prostatic cancer on
      digital rectal examination (DRE) or transrectal ultrasonography (TRUS). We
      evaluated 565 consecutive patients referred to us for prostatism, suspicious
      lesions on DRE, or an elevated serum PSA level. These patients do not represent a
      purely screened population. A detection rate of 38.4 percent was achieved by
      performing directed biopsies of suspicious lesions on DRE and/or TRUS, and
      systematic biopsies of all patients with serum PSA levels above 4 ng/mL. Among
      142 patients with serum PSA between 4.1 and 10 ng/mL, but without suspicion for
      cancer on DRE and TRUS (DRE- TRUS-), a large number of patients (6.2) were
      subjected to systematic biopsies to detect one cancer. A receiver-operating
      characteristics curve for PSA density (PSAD) applied to this population confirmed
      that the best cut-off point for biopsies was a PSAD of 0.15, below which only two
      of twenty-three cancers would have been missed, sparing biopsies in 77 of 142
      patients. A similar approach was applied to DRE- TRUS- patients with serum PSA
      levels above 10 ng/mL. The number of cancers in those with serum PSA between 10.1
      and 14 ng/mL was too low to establish a PSAD cut-off point. In patients with
      serum PSA above 14 ng/mL, the best PSAD cut-off point for biopsies was 0.3, below
      which two of thirteen cancers would have been missed, sparing biopsies in 19 of
      39 patients. We conclude that PSAD can safely reduce the number of patients
      subjected to systematic biopsies without significantly compromising cancer
      detection.

PMID- 7506854
TI  - Effect of finasteride on prostate-specific antigen density.
AB  - OBJECTIVE: Prostate-specific antigen density (PSAD) has been proposed as a
      diagnostic marker for prostate cancer. Because treatment with finasteride may
      affect PSAD differently in men with BPH compared with men with BPH plus prostate
      cancer, we evaluated the diagnostic utility of PSAD in men treated with
      finasteride for twelve months. METHODS: Data for this analysis were obtained from
      895 men with BPH enrolled in a twelve-month placebo-controlled North American
      study. Prostate volume was measured by magnetic resonance imaging and PSA was
      measured by the Hybritech immunoradiometric assay. RESULTS: Treatment with
      finasteride for twelve months increased the positive predictive value of PSAD for
      identifying the presence of prostate cancer from 14 percent to 30 percent. Using
      PSA values alone with a cutoff of 10 ng/mL at baseline and 5 ng/mL after twelve
      months of treatment, similar specificity and sensitivity could be achieved.
      CONCLUSION: The data suggest that adjustment of PSA values during treatment with
      finasteride can be used to maintain the diagnostic accuracy for prostate cancer
      while PSAD can be used to provide additional reassurance without requiring
      adjustment for treatment.

PMID- 7506857
TI  - [The pituitary glycoprotein hormones, alpha subunit].
AB  - Pituitary glycoprotein hormones FSH (follicle-stimulating hormone), LH
      (luteinizing hormone) and thyrotropic hormone, TSH (thyroid-stimulating hormone)
      are formed by two subunits: alpha which is essentially the same for all three
      hormones, and beta which is responsible for their biochemical specificity. The
      alpha subunit is from the quantitative aspect a very important secretion of the
      pituitary. Part of the alpha subunit produced in the pituitary is not used for
      the synthesis of hypophyseal glycoprotein hormones and is secreted in a pulsed
      way synchronously with the pulsed LH secretion into the peripheral blood stream.
      Levels of the free alpha subunit in the peripheral blood depend on a number of
      factors in particular age, sex and in women on the stage of the menstrual cycle.
      The physiological roles of the free alpha subunit are only partially known. It is
      assumed that the most important part is the participation in the modulation of
      the effect of hypophyseal glycoprotein hormones at the level of their peripheral
      tissues. During the last few years it was revealed, surprisingly, that the level
      of the free alpha subunit in plasma may be used as a tumour marker as this
      parameter rises during some pathological conditions, in particular in adenomas of
      the pituitary.

PMID- 7506855
TI  - Immunohistologic detection of prostate cancer pelvic lymph node micrometastases:
      correlation to preoperative serum prostate-specific antigen.
AB  - OBJECTIVE: To test the hypothesis that prostate cancer lymph node (LN)
      micrometastases, undetected by standard histology, might be found using sensitive
      immunohistologic methods and may correlate to preoperative prostate-specific
      antigen (PSA) levels. METHOD: Archival paraffin blocks of pelvic lymphadenectomy
      specimens from radical prostatectomy were blindly submitted for immunostaining
      using pan-cytokeratin monoclonal antibody SB-3, as well as antibodies directed
      against PSA. Automated immunostaining was performed on a Ventana Medical Systems
      320 immunostainer. As a positive control, 7 cases with known nodal metastases by
      standard histology were blindly analyzed and all has detectable micrometastases
      by this methodology. RESULTS: For 13 patients with PSA < 10.1 (8%) had LN
      micrometastases detected. For 10 patients with PSA between 10 and 20 and for 9
      patients with PSA > 20, no occult metastases were detected. We did find
      previously undetected prostate cancer (CaP) LN micrometastases in 1 of 32 (3%)
      clinically localized prostate cancer patients who had undergone radical
      prostatectomy. In many LNs, cytokeratin stains cross-reacted and stained
      individual plasma cells, whereas in the positive metastatic case, a cluster/nest
      of CaP cells were reactive. To the unfamiliar observer, the pitfall of false
      positive results because of nonspecific cytokeratin staining must be considered.
      These results are in exact agreement with another recent study which also found
      only a 3 percent incidence of unsuspected pelvic lymph node micrometastases in
      clinically localized CaP utilizing similar methods. CONCLUSIONS: Our hypothesis
      was not substantiated: LN micrometastases were uncommon and did not correlate to
      serum PSA. Unlike studies with breast cancer, occult micrometastatic nodal
      disease not appreciated by standard methods appears to be uncommon in clinically
      localized prostatic carcinoma.

PMID- 7506856
TI  - Surgical resection in patients with nonseminomatous germ cell tumor who fail to
      normalize serum tumor markers after chemotherapy.
AB  - OBJECTIVE: Patients with high-stage nonseminomatous germ cell tumors treated with
      platinum-based chemotherapy who have residual radiographic evidence of disease
      and fail to normalize tumor markers present a difficult clinical dilemma. Some
      authors feel that these patients are not appropriate surgical candidates. Our
      practice has been to offer certain patients salvage surgery in an attempt for
      cure. This report is designed to review that experience and critically analyze
      the results. METHOD: We report a series of 16 such patients with advanced-stage
      nonseminomatous germ cell tumors who had persistently elevated alpha fetoprotein
      and/or human chorionic gonadotropin. All underwent resection of all
      radiographically evident sites of residual disease following induction or salvage
      chemotherapy. RESULTS: Ten patients had only retroperitoneal (RP) metastasis. Six
      patients had more than one site of residual disease--4 RP and lung, 2 RP and
      liver. There were no postoperative deaths. The mean postoperative stay was eleven
      days (range 7 to 36 days). Six patients (37%) are alive and free of disease at a
      mean of seventy-four months following surgery (range 20 to 145 months). Five had
      RP disease only. Ten patients died of disease at a mean of eight months
      postoperatively (range 5 to 21 months). CONCLUSIONS: Patients with advanced
      nonseminomatous germ cell tumor who fail to normalize their serum tumor markers
      after adequate platinum-based chemotherapy should be considered for surgical
      resection of all radiographically evident residual disease. In select cases this
      practice offers the only viable chance for cure.

PMID- 7506858
TI  - [Computer-assisted management of anticoagulation therapy with dicoumarin. A new
      program].

PMID- 7506861
TI  - Virulence and susceptibility to phagocytosis of Pseudomonas pseudomallei R- and S
      forms for ground squirrels (Citellus citellus L.).
AB  - Virulence and susceptibility to phagocytosis of Pseudomonas pseudomallei R- and S
      forms for ground squirrels were studied. The alveolar macrophages and blood
      leucocytes (polymorphonuclear and mononuclear) was used. S-forms survived and
      multiplied intracellularly more actively in alveolar macrophages than R-forms and
      their virulence was considerably higher.

PMID- 7506859
TI  - Production and characterization of monoclonal antibodies differentiating
      subpopulations of porcine B lymphocytes in blood and lymphoid tissues.
AB  - Monoclonal antibodies (mAbs) against various subclasses of immunoglobulin
      molecules are important reagents for the characterization and differentiation of
      serum immunoglobulins (Ig) generated during immune responses. Furthermore, Ig
      specific mAbs can be powerful tools for the detection of B lymphocytes in blood
      and lymphoid organs. Here we describe two mAbs generated in our laboratories,
      named 1G6 and 2E8, which react with distinct epitopes on porcine immunoglobulin
      molecules. MAb 1G6 recognizes an epitope of an immunoglobulin chain with apparent
      molecular mass of 25 Kd. This chain represents an immunoglobulin light chain and
      might be the porcine equivalent of the murine and human kappa chain. MAb 2E8 is
      directed against porcine IgM molecules, recognizing an epitope of the porcine mu
      chain. The use of these mAbs was shown to avoid some common disadvantages of anti
      Ig polyclonal antisera, like the high background staining of cells and tissue
      culture sections in immunohistochemistry. Furthermore, the use of these mAbs in
      two-color flow cytometry (FCM) versus a polyclonal anti-porcine Ig antiserum
      enables distinct B-lymphocyte subpopulations in blood and lymphoid organs to be
      detected. Our mAbs seem therefore to represent important and powerful reagents to
      identify and characterize porcine Ig isotypes and surface-Ig positive porcine B
      lymphocytes; their discriminating power between distinct B lymphocyte
      subpopulations could prove useful in different fields of both applied and
      fundamental immunological research.

PMID- 7506860
TI  - Amylase-producing Bence Jones multiple myeloma with pancreatitis-like symptoms.
AB  - Amylase-producing tumors are mainly adenocarcinomas and, in rare instances,
      multiple myelomas. We describe here a first case of amylase-producing Bence Jones
      type myeloma with pancreatitis-like symptoms and the second in a Caucasian
      patient. The finding of salivary-type hyperamylasemia in a 72-year-old female
      with a possible pancreatitis made us suspect the diagnosis. Amylase production
      was observed in bone marrow cultures in which 96% of cellularity was composed of
      plasmablasts. Serum amylase level decreased when chemotherapy was given.

PMID- 7506862
TI  - Effect of C-6 on reverse transcriptase of some avian retroviruses.

PMID- 7506863
TI  - Pharmacological investigations with different protein kinase C inhibitors on IgE
      dependent and IgE-independent activation of human basophils.
AB  - In the present study different selective inhibitors of the multifunctional
      serine/threonine kinase protein kinase C (PKC) were investigated on classical
      activation pathways of basophils in comparison to the nonselective protein kinase
      inhibitor staurosporine. The potent inhibitors Ro 31-7549, Ro 31-8220, calphostin
      C and ilmofosine (BM 41.440), which show selectivity for PKC in vitro,
      significantly potentiated Fc epsilon RI-mediated histamine release up to 50% vs.
      controls at concentrations > 10(-7) mumol/l but were without any intrinsic
      histamine releasing activity. Direct activation of cellular PKC by phorbol ester
      was suppressed by all compounds apart from ilmofosine at the same concentrations.
      We did not observe statistically significant effects of selective PKC inhibitors
      on exocytosis induced by the peptide formylmeth-leu-phe (FMLP) or the ionophore
      A23187, whereas staurosporine potentiated the FMLP-induced histamine release in a
      dose-dependent fashion: maximum potentiation was 63.5 +/- 8.9% vs. control at 1
      mumol/l (n = 4). The findings suggest that PKC exhibits differential functions
      during biochemical events of stimulus-secretion coupling in human basophils
      supposedly by its distinct subtypes. With respect to the present data, TPA
      induced and IgE-mediated signals are not closely correlated.

PMID- 7506864
TI  - Bleomycin injury of the lung in a mast-cell-deficient model.
AB  - Lung mast cell hyperplasia and fibrosis is induced by bleomycin lung injury. The
      role of the mast cell in this process of injury and resultant fibrosis is
      unclear. Mutant mi/mi mice, profoundly mast-cell-deficient, were treated with
      intraperitoneal bleomycin and demonstrated minimal acute inflammatory and chronic
      fibrotic responses. Lung histamine values determined at 14 and 42 days after
      bleomycin injury in mi/mi mice were not increased compared to untreated mi/mi
      animals. However, lung histamine levels in normal mice demonstrated a 300%
      increase over controls on Day 14 after bleomycin injury, and then returned to
      baseline by Day 42. The mi/mi BAL cell recovery at 2 weeks after injury and lung
      hydroxyproline levels at 4 weeks after injury were not altered from baseline. The
      normal litter mates, in contrast, demonstrated significant increases compared to
      controls in both of these parameters (p < 0.01, p < 0.04). Although the mi/mi
      mouse is also deficient in basophils, natural killer cells and functional
      osteoclasts, there is no evidence of lowered pulmonary defense mechanism and
      neutrophils and alveolar macrophages are present in normal numbers. This
      investigation supports the hypothesis that the mast cell contributes to bleomycin
      induced lung injury and fibrosis.

PMID- 7506865
TI  - [Lectin histochemical studies on species differences in the mammalian trabecular
      meshwork].
AB  - Lectin histochemical studies were performed to clarify the species differences in
      the location of glycoconjugates in the trabecular meshwork (TM) of various
      mammals, i.e., the mouse, rat, rabbit, pig, and ox, to find an experimental model
      for human TM. Cryosections were made and stained with sixteen kinds of
      biotinylated lectin followed by an avidin-biotin-peroxidase complex (ABC). Strong
      positive reactions in the TM of all 5 kinds of mammals were observed for ConA,
      PHA-E4, PHA-L4, WGA, ABA, LCA, RCA 60, RCA 120, DSA, and SSA. The TM of the 5
      kinds of mammals was weakly positive for Lotus. Rabbit, pig and ox TM were
      positive for MAM and others were negative. Rabbit, pig and ox TM were weakly
      positive for PNA and were negative in the other's. Rat TM was weakly positive for
      SBA and was negative in the other's. The TM of all 5 kinds of mammals was
      negative for UEA-I and DBA. It could be concluded that species difference exists
      in lectin binding site in the TM.

PMID- 7506866
TI  - [Antibiotic prophylaxis for transurethral resection of the prostate--comparison
      of oral administration therapy with intravenous administration therapy].
AB  - To compare the prophylactic effect of oral and intravenous antibiotics against
      postoperative fever and urinary tract infection (UTI) after transurethral
      resection of the prostate (TUR-P), we conducted a multi-center prospective
      randomized study. The incidence of pyrexia over 38 degrees C was defined as the
      primary endpoint. One hundred and fifty patients with sterile urine before TUR-P
      were entered into this study. The patients were allocated randomly into the two
      arms; arm A cefotiam 4 g a day for 7 days, arm B tosufloxacin 300 mg a day for 7
      days, based on the stratification into the 4 groups determined with/without
      preoperative indwelling catheters and with/without the history of preoperative
      UTI. Of these patients, 143 were eligible. We divided 124 patients without
      preoperative UTI and without indwelling catheters as the "low risk group", and
      the other 19 patients with preoperative UTI and/or with indwelling catheters as
      the "high risk group". In the low risk group, 9 patients out of 63 (14.3%) in arm
      A and 6 out of 61 (9.8%) in arm B had pyrexia during 7 postoperative days. The
      incidence of fever in arm B was 4.4% less than that in arm A and the 95%
      confidence limit was from -7% to 16%. In the high risk group, 4 out of 11 (36.4%)
      patients in arm A and none of 8 in arm B had fever but the difference was not
      significant. The incidence of post operative UTI in the low risk group on the 4
      to 5, 9 to 12, 23 to 26 and 37 to 40 postoperative days was 8.3, 16.4, 25.0 and
      23.9% in arm A and 6.7, 16.7, 29.6 and 36.7% in arm B, respectively. The
      prophylactic effect of oral administration of tosufloxacin is equivalent to that
      of the intravenous administration of cefotiam. The use of oral antibiotics is
      beneficial to reducing the cost of medication.

PMID- 7506867
TI  - [A case of stage IIIB2 infantile yolk sac tumor of testis achieved complete
      remission by "COMPE" chemotherapy].
AB  - A case of metastatic infantile yolk sac tumor of testis is reported herein. The
      patient was 23 months old with a painless swelling of the right scrotal contents.
      Histological examination revealed yolk sac tumor. Six months later, the serum
      alpha-fetoprotein (AFP) was re-elevated and solitary lung metastasis had
      developed. After 4 courses of chemotherapy with cisplatin (CDDP), vincristine
      (VCR), methotrexate (MTX), peplomycin (PEP) and Etoposide (COMPE), serum AFP was
      normalized and lung metastasis disappeared. He has shown no evidence of disease
      for 5 years with normal physical growth. Aggressive chemotherapy including CDDP
      might be used for Stage III infantile testicular cancer.

PMID- 7506868
TI  - [Ofloxacin concentration in prostatic tissue].
AB  - The concentration of ofloxacin in prostatic tissue and serum was determined in
      order to evaluate the permeability of ofloxacin into prostatic tissue in patients
      with benign prostatic hypertrophy. Ofloxacin was administered orally at a dose of
      200 mg several hours before subcapsular prostatectomy. The determination was
      performed in the surgically removed adenoma and in the serum taken one hour
      before and at the removal of the adenoma. The peak level in the prostatic tissue
      was 1.46 microgram/g at 4.5 hour after the administration. The ratio of prostatic
      tissue level to the serum level was 1.00. In conclusion, ofloxacin was thought to
      be very useful for the treatment of acute and chronic prostatitis.

PMID- 7506869
TI  - [Clinical study of renal cell carcinoma].
AB  - Previously, we reported the effects of human lymphoblastoid interferon (HLBI),
      using a transplantable human renal cell carcinoma strain (AM-RC-3) in nude mice
      established in our laboratory. An overall anticancer effect was found from its
      combination with UFT (Ft-207t uracil). In the present investigation, we examined
      the clinical effectiveness when HLBI was administered alone or in combination
      with UFT to the patients. Seventy-three patients who had undergone curative
      surgery were divided into 3 groups, according to the type of adjuvant therapy.
      The HLBI group consisted of 38 patients, including those administered the agent
      alone over 50 times for more than six months, and or those to whom it was given
      in combination with UFT. The second group of 23 patients had been treated with
      hormones, radiotherapy, or with an anticancer drug (Fluoride pyrimidine group),
      while the last group of 17 patients underwent no postoperative adjuvant therapy.
      The survival rate calculated by the Kaplan-Meier method revealed no significant
      effects of HLBI on the survival period, but a significant difference (p < 0.05)
      was found in the HLBI group compared to the other groups in terms of much higher
      non-recurrence rate. When HLBI was administered alone or in combination with UFT,
      a definite anticancer effect was seen in 6 (complete response 3, partial response
      2, minor response (MR) 1, no change 5, progression of disease 14) of the 25
      treated patients. Fourteen of the 25, treated patients had postoperative
      recurrence, and 11 patients had distant metastases, at the time of diagnosis
      which were considered to be progressive and measurable lesions. In 6 patients the
      response was better than MR, with the effective rate being 24%. Four of the 6
      patients had received HLBI in combination with UFT, which suggests a clinical
      effect in this combination. However, the effectiveness was limited to the lung
      lesions, more effective treatment of the lesions in other sites is required.

PMID- 7506870
TI  - [Studies of combined treatment of radiofrequency hyperthermia with anticancer
      agents or irradiation for invasive bladder cancer].
AB  - Using an in vitro colony forming assay system, the cytotoxic effects of
      anticancer agents alone, adriamycin (ADM) and bleomycin (BLM), and the combined
      effects of hyperthermia and anticancer agents on cultivated KK-47 cells were
      investigated. When the hyperthermia was combined with various concentrations of
      ADM ranging from 0.005 to 0.1 microgram/ml and BLM from 0.01 to 1.0 microgram/ml,
      enhanced cell killing effects were obtained at the concentration of less than
      0.02 microgram/ml of ADM and with an increase of BLM concentration. In DNA
      specimens obtained from the livers of chick embryos inoculated with human tumor
      cultivated cells, the polymerase chain reaction technique was used to amplify a
      DNA fragment specific to the beta-globin gene. By detecting these amplified DNA
      fragments, the feasibility of efficiently detecting metastatic cells present in
      chick embryo was demonstrated in vivo. Hyperthermic therapy showed inhibitory
      effects on the growth of metastasized cultivated cells in a thermal dose
      dependent manner. Combination therapy of ADM, mitomycin and carboplatin and
      hyperthermia had an enhanced inhibitory activity on the growth of metastasized
      cultivated human tumor cells derived from bladder cancer. Hyperthermia using
      radiofrequency-capacitive heating in combination with irradiation or anticancer
      agents, was performed in a total of 56 patients with T2 to T4 invasive urinary
      bladder cancer. A tumor regression rate of 50 percent or more was obtained in 21
      of these 56 patients. We have to follow up the patients for longer periods more
      precisely to evaluate the role of these treatments.

PMID- 7506871
TI  - Anion exchanger 1 in human kidney and oncocytoma differs from erythroid AE1 in
      its NH2 terminus.
AB  - Acid-secreting intercalated cells of the kidney collecting duct and tumor cells
      of renal oncocytoma express an anion exchanger that is immunologically related
      but not identical to the chloride-bicarbonate anion exchanger of erythrocytes
      (AE1). In this study, we have mapped the binding site of a monoclonal antibody
      against erythroid AE1 that does not react with either intercalated cells or
      oncocytoma. The epitope is located close to the NH2 terminus of AE1, indicating
      that AE1 in intercalated cells and oncocytoma differs in its NH2 terminus from
      erythroid AE1. This conclusion was supported by an antibody directed against
      residues 1-14 of erythroid AE1 that does not react with intercalated cells in
      oncocytoma. Polymerase chain reaction performed with mRNA from a human kidney
      revealed that the sequence containing the codons for Met-1 and Met-33 in
      erythroid mRNA is missing in the kidney transcript, whereas the sequence coding
      for Met-66 is present. DNA sequence data derived from cloning the 5' end of the
      human kidney AE1 mRNA clearly showed that the 5' untranslated region comprises
      part of intron 3, the complete exon 4 that is followed by exon 5 containing Met
      66 as the site of translation initiation. Altogether, the results indicate that
      AE1 in the human kidney is an amino-terminally truncated form of erythroid AE1
      that is restricted to the basolateral membrane domain of the acid-secreting
      intercalated cells of the collecting duct and is also expressed in oncocytoma.

PMID- 7506872
TI  - Structural-functional correlation in chinchilla long loop of Henle thin limbs: a
      novel papillary subsegment.
AB  - The ultrastructural characteristics of thin limb subsegments from chinchilla long
      loops of Henle were studied in perfusion-fixed kidneys and in isolated perfused
      tubules. In sections from the perfusion-fixed kidneys, we noted types I, II, III,
      and IV thin limb epithelia similar to those previously identified in other rodent
      species. Sections from the deepest 20% of the papillary tip, however, revealed
      only a single thin limb epithelial type, which had a combination of structural
      characteristics distinct from previously identified thin limb subtypes. This
      "papillary type" epithelium had relatively tall cells and a complex cellular
      organization with extensive interdigitation, numerous shallow tight junctions,
      and microvilli. In single-tubule studies, thin limb segments dissected from
      different levels of the outer and inner medulla were perfused in vitro for
      osmotic water permeability (Pf) measurements and were fixed for ultrastructural
      examination. Long-loop thin descending limbs (LDL) dissected from the outer
      medulla (Pf, 2,637 +/- 336 micron/s) had type II epithelium. LDL dissected from
      the middle of the inner medulla (Pf, 1,570 +/- 76 microns/s) had a type III
      epithelium. LDL segments dissected from the deepest 20% of the inner medulla had
      a low but nonzero Pf (68 +/- 9 micron/s) and had the same novel papillary type
      epithelium seen in sections from fixed kidneys. Thin ascending limbs dissected
      from inner 50% of the inner medulla had essentially zero Pf (8 +/- 4 micron/s)
      and had a type IV epithelium. Immunohistochemical localization of CHIP28 water
      channel protein confirmed the presence of CHIP28 in thin descending limbs
      throughout the outer 75% of the inner medulla, whereas labeling was essentially
      absent in the deep inner medulla where the low-PfLDL (novel papillary type
      epithelium) is located.

PMID- 7506874
TI  - Anaphylactic reaction to aprotinin during cardiac surgery.

PMID- 7506873
TI  - Abnormal renal hemodynamic response to reduced renal perfusion pressure in
      diabetic rats: role of NO.
AB  - Diabetic rats manifest abnormal renal hemodynamic responses, with persistent
      renal vasodilation at reduced renal perfusion pressures. We hypothesized that in
      diabetes, renal hemodynamics are modulated by increased activity of the
      endogenous vasodilator, NO. In anesthetized Munich-Wistar rats, after 6 wk of
      streptozotocin-induced, insulin-treated diabetes, and in age-matched, nondiabetic
      littermates (n = 7-8), basal renal hemodynamics and responses to graded
      reductions in renal perfusion pressure were determined before and after
      intrarenal arterial infusion of the NO synthase inhibitor, NG-nitro-L-arginine
      methyl ester (L-NAME). An identical protocol was followed in a second cohort of
      rats pretreated with indomethacin (4 mg/kg iv). Diabetic rats demonstrated
      hyperglycemia, renal enlargement, hyperfiltration, and increased urinary
      excretion of the stable NO metabolites, NO2 and NO3. L-NAME eliminated basal
      hyperfiltration in diabetic rats, and L-NAME, but not indomethacin, also
      eliminated persistent renal vasodilation at reduced renal perfusion pressure. We
      conclude that in a rat model of diabetes, increased endogenous NO activity may
      play a role in basal hyperfiltration and in the persistent renal vasodilatation
      manifested at reduced renal perfusion pressures.

PMID- 7506876
TI  - Invited discussion: the complexity of insulin-like growth factors in bone growth
      and remodeling.

PMID- 7506875
TI  - [Syncope in pediatric age. Diagnostic evaluation].
AB  - Syncope is characterized by a transient loss of consciousness and the loss of
      postural tone to varying degrees and intensities. The cause could be associated
      with cardio-vascular diseases or non-cardiovascular problems. A third group
      includes unexplained situations, in spite of the fact that a complete medical and
      laboratory examination has been performed. In this manuscript, three diagnostic
      protocols to be followed, depending on the degree of severity, are proposed.
      Patient history, physical examination and basic laboratory tests are the
      preliminary steps for the simple cases (Protocol I). In syncope of intermediate
      degree, Protocol II is recommended. This protocol consists of a complete
      cardiologic study (electrocardiogram, Holter monitoring, and echocardiogram),
      neurologic evaluation (electroencephalogram during sleep, CT scan, and magnetic
      resonance imaging scan) and non-invasive testing of the autonomic function,
      especially the tilttable test. Hemodynamic studies and electrophysiological
      testing (Protocol III) is indicated for patients with severe and recurrent
      syncope, some of which are at very high risk of sudden death. The therapy depends
      on the diagnostic tests. It may be as simple as a change in habits or it could
      include pharmacological treatment such as the use of an anti-arrhythmic agent.
      Some cases require pacemaker implantation, while others mandate surgical
      procedures.

PMID- 7506879
TI  - Haemorrhagic disease of the newborn: a review of 127 cases.
AB  - A review of 127 infants with haemorrhagic disease of the newborn (HDN) is
      presented. The case definition of HDN used in the selection of patients was
      bleeding during the 1st week of life in a newborn with normal platelet count,
      normal peripheral blood smear and complete clinical response to parenteral
      vitamin K. Equivocal cases with respect to cause of bleeding were excluded. The
      eligible cases consisted of 0.9% of all admissions to the unit and the
      male:female ratio was 1.8:1. Most were from families of low economic status and
      poor educational background. Omission of vitamin K prophylaxis and exclusive
      breastfeeding were the commonest antecedents. The mean (SE) gestation and
      admission weight were 39.3 (0.2) weeks and 2981 (78) g, respectively. One hundred
      and two (80.3%) had classical HDN with a mean (SE) age at onset of 63 (4.4)
      hours. Gastro-intestinal bleeding was the commonest observation. Thirty-three
      infants (26%) died, most of them from exsanguination. There is a need for well
      designed work to determine the magnitude of the problem, including that of late
      onset HDN, the antecedent risk factors, the preferred route for administering
      prophylactic vitamin K and a clear policy guideline on prevention of the disease.

PMID- 7506877
TI  - Expression of immunologically relevant endothelial cell activation antigens on
      isolated central nervous system microvessels from patients with multiple
      sclerosis.
AB  - Activation of the vascular endothelium is thought to be an important facet of
      inflammation, thrombosis, and vasculitis. Activated endothelial cells express a
      number of immunologically relevant surface markers not expressed by normal
      endothelial cells. Many of these surface antigens are thought to augment adhesion
      reactions and migration. Our results show that endothelial activation may play a
      central role in the pathogenesis of multiple sclerosis (MS). Normal human central
      nervous system microvessels isolated from autopsy material do not express
      endothelial cell activation markers, including the adhesion proteins vascular
      cell adhesion molecule-1 (VCAM-1) and endothelial cell leukocyte adhesion
      molecule-1 (E-selectin/ELAM-1). They exhibit little to no constitutive expression
      of immunoreactive intercellular adhesion molecule-1 (ICAM-1) or the urokinase
      plasminogen activator receptor. Control microvessels exhibit no major
      histocompatibility complex (MHC) class II antigen. MS microvessels express
      significant levels of MHC class II antigens, ICAM-1, VCAM-1, and urokinase
      plasminogen activator receptor. E-selectin was expressed by 3 of 5 MS brains
      tested. Histologically unaffected areas of MS brain expressed less VCAM-1, ICAM
      1, and E-selectin than did microvessels from periplaque zones. However, MHC class
      II antigens and urokinase plasminogen activator receptor were increased in areas
      exhibiting little to no evidence of leukocyte infiltration. When microvessels
      were examined for dual expression of activation markers, we found that in
      periplaque areas, 50% of microvessels coexpressed HLA-DR and VCAM-1, 28% of
      microvessels coexpressed HLA-DR and urokinase plasminogen activator receptor, and
      43% of microvessels coexpressed HLA-DR and ICAM-1.

PMID- 7506878
TI  - Aspartame has no effect on seizures or epileptiform discharges in epileptic
      children.
AB  - The effects of aspartame (L-aspartyl-L-phenylalanine methyl ester; APM) on the
      neurological status of children with well-documented seizures were examined in a
      randomized, double-blind, placebo-controlled, crossover study. We report on 10
      children (5 boys, 5 girls, ages 5-13 yr) who were tested for 2 weeks each on APM
      and placebo (single morning dose, 34 mg/kg). Seven children had generalized
      convulsions with 4 also having absence episodes. One child had absence seizures
      and 2 had complex partial seizures only. On each arm of the study, children were
      admitted to the hospital for a standard 21-lead electroencephalogram (EEG),
      continuous 24-hour cassette EEG, and determination of biochemical variables in
      plasma and urine. Subjects completed the Subjects Treatment Emergent Symptoms
      Scale (STESS) and parents the Conners Behavior Rating Scale. There were no
      significant differences between APM and placebo in the standard EEG or 24-hour
      EEG. No differences were noted for the STESS or the Conners ratings, and no
      differences were noted for any of the biochemical measures (except for expected
      increases in phenylalanine and tyrosine after APM). Our findings indicate that,
      in this group of vulnerable children, APM does not provoke seizures.

PMID- 7506880
TI  - Poliomyelitis in Malaysia: two confirmed cases after 6 years without polio.
AB  - Poliomyelitis in Malaysia has not been reported since 1986. We report two cases
      of poliomyelitis in non-immunized children whose parents, though relatively
      educated, opted not to vaccinate their children for socio-cultural reasons. This
      recent trend may interfere with our attempts to eradicate poliomyelitis globally
      by the year 2000. The clinical features, pathophysiology and differential
      diagnosis are discussed.

PMID- 7506881
TI  - The pattern of infant and childhood mortality in Upper River Division, The
      Gambia.
AB  - A system has been established to document births and deaths in children in a
      large, rural, West African population, using community reporters. Causes of death
      in children under the age of 5 years were investigated using post-mortem
      questionnaires completed by field assistants. There was a marked seasonal
      incidence of all major causes of death with peak rates in the rainy season. Acute
      lower respiratory infections (ALRI) were the most frequent cause of death in
      children under 5 years of age. Other major causes of death were malaria, acute
      gastro-enteritis and chronic diarrhoea with malnutrition. Mortality from all the
      major causes of death decreased with increasing village size. Our findings have
      implications for interventions against childhood mortality.

PMID- 7506882
TI  - Transverse myelitis in a child with Down's syndrome and schistosomal colitis.
AB  - This is a report of an 11-year-old Saudi child with Down's syndrome who presented
      with a 3-month history of diarrhoea, anal fissures and bleeding per rectum. The
      child was investigated in a local hospital and found to have evidence of colitis.
      He was referred to our hospital for further investigation and management. Six
      weeks prior to transfer, the child developed weakness of the lower limbs
      resulting in inability to walk. The child was found to have Schistosoma mansoni
      colitis complicated by spinal cord involvement presenting as transverse myelitis.
      Two 1-day courses of therapy with praziquantel resulted in a satisfactory
      recovery, enabling the child to walk by himself.

PMID- 7506883
TI  - Determinants of neonatal mortality in central Sudan.
AB  - A follow-up study was conducted in six community health centres during the period
      April 1989 to March 1990 to determine the risk factors which influence neonatal
      survival in central Sudan. The estimated neonatal mortality rate ranged between
      20.0 and 36.0 per 1000 live births per year, and the major cause of death was
      tetanus neonatorum (29% of neonatal deaths). The mortality rate was lowest when
      tetanus toxoid was received during pregnancy and the umbilical cord was cleaned
      by a modern hygienic method (mortality rate of 11 per 1000). In contrast, the
      mortality rate was highest when no tetanus toxoid was received and no or
      traditional cord cleaning was used (mortality rate of 62 per 1000; relative risk
      (RR) = 5.6, 95% confidence interval (CI) 2.0-14.9). The major predictors of
      neonatal mortality were tetanus, short birth-to-conception interval, multiparity,
      reported malaria during pregnancy, low birthweight, low maternal weight and low
      socio-economic status. The population attributable risks were high, and the
      preventable factors collectively accounted for 93.5% of neonatal mortality. Safe
      deliveries and wider immunization coverage are needed to control neonatal tetanus
      in this community. Other interventions to lower neonatal mortality in central
      Sudan should include accessible family planning programmes and measures to lower
      the incidence of low birthweight.

PMID- 7506884
TI  - Management of appendicular mass in children.
AB  - Of 66 children under 12 years of age treated for appendicular mass, seven
      underwent immediate surgery, and two of them developed post-operative wound
      infection. The remaining 59 children had conservative management which consisted
      of bedside observation of vital and abdominal signs, intravenous fluids and
      triple antibiotic therapy with ampicillin, gentamicin and metronidazole. The
      majority of the children responded well to this method, and in 54 (91.5%) the
      mass resolved completely. Two patients did not respond and required drainage of
      the abscess. Three other children responded initially to conservative management,
      but returned with recurrence of the mass. After their discharge from hospital,
      only 14 (24.5%) children returned for interval appendicectomy, which revealed
      that 13 of the 14 appendices excised still showed patent lumens. This study
      showed that conservative management of appendicular mass is safe and effective in
      children. In view of the patent appendicular lumen in those who had complete
      resolution of the mass, and the attendant risk of re-infection, interval
      appendicectomy appears to be desirable.

PMID- 7506885
TI  - Congenital syphilis: the diagnostic value of the rheumatoid factor in symptomatic
      patients.
AB  - The rheumatoid factor (RF) latex test was used as a side-room investigation for
      congenital syphilis. Thirty-four infants aged 0-4 months with suggestive clinical
      signs and unknown serological tests for syphilis were studied. Nineteen were
      subsequently diagnosed as having congenital syphilis on the basis of positive
      serology, while 15 infants had other conditions. The sensitivity of the RF latex
      test was 95% with a specificity of 80%. Reactive tests were seen only in neonates
      with congenital infections (p < 0.001). The total IgM test had a similar
      sensitivity in the diagnosis of congenital syphilis but its specificity (14%) was
      significantly less (p < 0.001). In areas where the prevalence of congenital
      syphilis is high, the RF latex test is useful for rapid diagnosis of the
      condition while confirmatory tests are awaited.

PMID- 7506886
TI  - Value of serum C-reactive protein concentrations in febrile children without
      apparent focus.
AB  - We examined the value of serum C-reactive protein (CRP) in febrile children
      without an apparent focus of infection, (i) as a tool to differentiate
      bacteraemia and bacterial infection from a non-bacterial illness (NBI), and (ii)
      as an indicator of recovery or complications. Included in the study were 100
      children up to the age of 3 years with a temperature of > or = 38.5 degrees C,
      without an apparent focus. The serum CRP concentration was measured on days 1, 3
      and 5 of evaluation and correlated with the final diagnosis and outcome. The
      serum CRP was 40 mg/l and above in 95% of patients (18/19) with bacteraemia and
      also in seven of the eight with purulent meningitis, while it was < 40 mg/l in
      84% of patients (52/62) with NBI (mean (SD) 22 (28.6) mg/l). The mean serum CRP
      concentration among six children with a culture-positive urinary tract infection
      (16.3 (8.3) mg/l) and five with otitis media (9 (5.7) mg/l) was similar to those
      with NBI. The sensitivity of serum CRP > or = 40 mg/l for diagnosis of
      bacteraemia was 95% and the positive predictive value 67%. On serial monitoring,
      a fall in the CRP concentration was a sensitive indicator of recovery from
      infection and provided the earliest clue to therapeutic response long before a
      fall in temperature.

PMID- 7506887
TI  - Adolescent pregnancy in Grenada.
AB  - A retrospective review of adolescent deliveries (maternal age range: 12-19 years)
      at the maternity unit of the main General Hospital, Grenada, was undertaken for
      the years 1987 and 1988 using the delivery room register and hospital medical
      records. These mothers were compared with women who delivered during the same
      period but were aged between 20 and 30 years. Of the 3203 deliveries which
      occurred during the study period, 613 (20%) involved adolescents, giving a
      prevalence rate of one in five pregnancies. chi 2 and Fisher's exact test
      analyses revealed that pregnancies occurring in younger adolescents (age less
      than 16 years, n = 58) carried an increased risk of preterm labour, operative
      delivery, prematurity, small-for gestational age infants, asphyxia and perinatal
      mortality when compared with the 'optimum reproductive age group'. Older
      adolescents (16-19 years, n = 555) had a higher risk of pregnancy induced
      hypertension but otherwise compared well with the optimal reproductive age group.
      Adolescent pregnancy is very prevalent in Grenada and the reproductive outcome
      for young adolescents < 16 years of age is relatively poor.

PMID- 7506888
TI  - Antigenuria in healthy Papua New Guinean children with nasal Haemophilus
      influenzae type b carriage.
AB  - In 100 healthy children under the age of 3 years living in the vicinity of
      Goroka, Papua New Guinea, the nares were cultured for Haemophilus influenzae type
      b (Hib), and a urine sample was obtained for measurement of Hib polysaccharide
      (PS) by ELISA. Hib carriage was detected in nine children and Hib PS was detected
      in the urine of 11. Hib PS was found in seven of nine Hib nasal carriers compared
      with four of 91 healthy children without Hib in their nares (p < 0.001). The
      range of urine antigen concentrations in the two groups was similar (0.6 to 2.7
      ng/ml). The relative risk of antigenuria in the carriers, compared with the
      children with negative nares cultures, was 58 (95% confidence interval, 10.5
      324). These data extend previous observations from Hib carriers studied in the
      United States and show that Hib carriage in children from a developing country is
      associated with antigenuria. Further studies are needed to determine whether
      carriers and patients can be differentiated by differences in the magnitude of
      the concentration of Hib PS excreted in urine.

PMID- 7506889
TI  - Acute intravascular haemolysis in glucose-6-phosphate dehydrogenase deficiency.
AB  - Thirty-five children with G6PD deficiency, who presented with acute intravascular
      haemolysis, were evaluated to define its aetiology, clinical features and
      ultimate outcome. All were boys with ages ranging from 6 months to 12 years.
      Pallor of abrupt onset and passage of cola-coloured urine were universal
      presenting symptoms. Incriminating factors responsible for haemolysis include
      hepatitis (7), malaria (4), bacterial sepsis (3) and drug intake (24), with more
      than one predisposing condition existing in some children. Marked elevations in
      serum bilirubin, coinciding with intravascular haemolysis, was a feature in all
      the seven children with hepatitis. Azotaemia was noted in 20 patients, of whom 14
      did not have oliguria. All four children with malaria presented with protracted
      renal failure. Therapy focused on maintaining a high urine output in those
      without oliguria. A total of 15 peritoneal dialyses and five haemodialyses were
      required in six patients with acute renal failure, all of whom were oliguric.
      Supportive therapy consisted of blood transfusions and treatment of the
      predisposing diseases. Thirty-two children recovered completely while three died,
      the cause of death being severe anaemia and congestive cardiac failure, malaria
      with oliguric renal failure and hepatic encephalopathy, respectively.

PMID- 7506890
TI  - Unusual presentation of cytomegaloviral infection in a 5-month-old baby: case
      report.
AB  - Painful restricted movements of the extremities, hyperpigmentation over swollen
      joints, and a sclerema-like feel to the skin with increased serum triglyceride
      was seen in a 5-month-old baby with postnatal CMV infection. In an infant with
      pseudoparalysis of the limbs, the possibility of CMV infection has to be
      considered.

PMID- 7506891
TI  - Bone changes in Herpes simplex infection mimicking congenital syphilis: case
      report.
AB  - A great many perinatal infections may be missed, especially during the early
      months of life, owing to their diverse modes of presentation. A simple skeletal
      survey is a helpful radiological study, in addition to virological and
      serological suspected Herpes simplex infection.

PMID- 7506892
TI  - Recognition of illness in very young infants by inexperienced health workers.
AB  - To determine whether inexperienced health workers can recognize severe infection
      in infants less than 3 months of age, a study was conducted of 200 infants with
      cough, fever or 'not feeling well'. The presence or absence of five symptoms:
      cough, difficulty in breathing, feeding problem, fever or history of convulsions,
      and ten signs: appearing ill, respiratory rate > or = 60/min, chest indrawing,
      grunting, cyanosis, wheeze, lethargy, 'too hot', 'too cold' or abdominal
      distension, were recorded by a health worker, who made a diagnosis of 'ill' or
      'mildly ill'. Each infant was then reviewed by an experienced paediatrician who
      made a diagnosis of 'ill' (pneumonia, sepsis, meningitis or other severe illness)
      or 'mildly ill'. Using these diagnoses as the 'gold standard', the sensitivity,
      specificity, and positive predictive values of each parameter were calculated. In
      89% of the 200 infants, the health worker made the correct diagnosis. Forty
      infants were admitted. In 36 instances (90%) the health worker made the correct
      decision. The most discriminating symptoms and signs were 'not feeding well',
      'appears ill', chest indrawing and grunting. A respiratory rate > or = 60/min was
      78% sensitive and 69% specific. Our study suggests that inexperienced health
      workers can recognize severe illness in infants under 3 months of age.

PMID- 7506893
TI  - Pulmonary alveolar microlithiasis in a Saudi child and two cousins.
AB  - Pulmonary alveolar microlithiasis is a rare disease and only 32 cases have been
      reported in children under 12 years of age. The first report on Saudi children
      with this disorder and on affected cousins is presented, supporting the possible
      hypothesis of it being an autosomal recessive disorder. The importance of
      differentiating it from other conditions, particularly pulmonary tuberculosis,
      and the current approach to diagnosis and management are discussed.

PMID- 7506894
TI  - Protective effect of picolinic acid on mice intracerebrally infected with lethal
      doses of Candida albicans.
AB  - We have studied the effects of picolinic acid (PLA), a product of tryptophan
      degradation, on mouse susceptibility to intracerebral infection with Candida
      albicans. We show that intraperitoneal administration of PLA significantly
      enhances the median survival time of mice inoculated with the lethal challenge.
      Furthermore, intracerebral administration of this agent induces a protective
      state against the local lethal infection, the phenomenon depending upon the
      administration schedule and doses of PLA employed. According to survival data,
      yeast growth in the brain as well as yeast colonization of the kidneys are
      drastically reduced in PLA-treated mice compared with those for untreated
      controls. Northern (RNA) blot analysis of brain tissues demonstrates that mRNA
      levels specific for tumor necrosis factor and interleukin 1 are augmented and
      induced, respectively, after inoculation of PLA. These results indicate that PLA
      has a protective effect likely involving elicitation of a cytokine response in
      vivo against fungal infections.

PMID- 7506895
TI  - 16S rRNA-targeted polymerase chain reaction and oligonucleotide hybridization to
      screen for Azoarcus spp., grass-associated diazotrophs.
AB  - Phylogenetic analyses after reverse transcriptase sequencing of 16S rRNA of
      nitrogen-fixing, grass-associated Azoarcus strains confirmed their affiliation to
      the beta subdivision of the Proteobacteria. Strains representing three different
      species formed a phylogenetically coherent unit related to Rhodocyclus purpureus,
      with actual percent similarities among the three sequences ranging from 93.1 to
      97.3%. Within variable regions V2 and V5, we found stretches of sequences
      considerably conserved within the genus Azoarcus but differing from most other
      gram-negative bacteria, with the specificity being enhanced when different
      regions were combined. Genus-specific primers selected from both regions
      amplified fragments from all but one Azoarcus species in polymerase chain
      reactions (PCR) but not from any reference strain tested. Primers of lesser
      specificity generated fragments from members of all five Azoarcus species as well
      as from some reference strains. Those unspecific amplifications could be
      differentiated by oligonucleotide hybridization, detecting only fragments
      generated from Azoarcus strains except strain 6a3, which represents the same
      group which could not be detected by genus-specific PCR. Thus we propose the
      application of PCR amplification with 16S rRNA-targeted, genus-specific primers
      in combination with hybridization of a 16S rRNA-targeted oligonucleotide to PCR
      generated fragments as diagnostic tests; this allows an initial screening for
      presence of members of the genus Azoarcus.

PMID- 7506896
TI  - Distribution of sulfate-reducing bacteria, O2, and H2S in photosynthetic biofilms
      determined by oligonucleotide probes and microelectrodes.
AB  - The vertical distribution of sulfate-reducing bacteria (SRB) in photosynthetic
      biofilms from the trickling filter of a sewage treatment plant was investigated
      with oligonucleotide probes binding to 16S rRNA. To demonstrate the effect of
      daylight and photosynthesis and thereby of increased oxygen penetration, we
      incubated two 4-mm-thick biofilm samples in darkness or exposed to light at
      natural intensity. Gradients of O2, H2S, and pH were examined with
      microelectrodes during incubation. The samples were subsequently frozen with
      liquid nitrogen and sliced on a cryomicrotome in 20-microns vertical slices.
      Fluorescent-dye-conjugated oligonucleotides were used as "phylogenetic" probes to
      identify single cells in the slices. Oligonucleotide sequences were selected
      which were complementary to short sequence elements (16 to 20 nucleotides) within
      the 16S rRNA of sulfate-reducing bacteria. The probes were labeled with
      fluorescein or rhodamine derivatives for subsequent visualization by
      epifluorescence microscopy. Five probes were synthesized for eukaryotes,
      eubacteria, SRB (including most species of the delta group of purple bacteria),
      Desulfobacter spp., and a nonhybridizing control. The SRB were unevenly
      distributed in the biofilm, being present in all states from single scattered
      cells to dense clusters of several thousand cells. To quantify the vertical
      distribution of SRB, we counted cells along vertical transects through the
      biofilm. This was done in a blind experiment to ascertain the reliability of the
      staining. A negative correlation between the vertical distribution of positively
      stained SRB cells and the measured O2 profiles was found. The distribution
      differed in light- and dark-incubated samples presumably because of the different
      extensions of the oxic surface layer. In both cases the SRB were largely
      restricted to anoxic layers.

PMID- 7506897
TI  - Ribotypes and plasmid contents of Vibrio anguillarum strains in relation to
      serovar.
AB  - Eighty-six strains of the 10 major agglutination types of Vibrio anguillarum
      (serovars O1 to O10) and 6 nontypeable strains of V. anguillarum have been
      characterized by ribotyping with a probe complementary to 16S and 23S rRNA of
      Escherichia coli and by plasmid profile analysis. Forty-four different ribotypes
      were observed with the restriction enzyme HindIII. Ribotype similarity was
      compared by using the Dice coefficient (Sd), and three significantly different
      levels of homogeneity within the V. anguillarum serovars were observed (serovars
      O1, O3A, O7, and O9, Sds of > 90%; serovars O2B, O4, and O10, Sds of 80 to 90%;
      serovars O2A, O3B, O5, and O8, Sds between 46 and 70%). None of the ribotype
      patterns of V. anguillarum strains were observed among 20 other Vibrio strains
      typed for comparison. By cluster analysis, the V. anguillarum strains were
      divided into a main cluster containing 83 strains, while all strains of serovar
      O3B, one strain (each) of serovars O2A, O5, and O8, and a nontypeable strain were
      separated from this cluster by at least 15% difference in similarity
      coefficients. Plasmids were demonstrated in only six strains other than serovar
      O1. In serovar O1, a 67- to 70-kilobase-pair (kb) plasmid molecule was present in
      17 of 19 strains tested; of the two remaining strains, one strain harbored two
      plasmids (45 and 6.5 kb) and one strain had no plasmids.

PMID- 7506898
TI  - Isolation of Lactococcus lactis subsp. cremoris from nature by colony
      hybridization with rRNA probes.
AB  - Lactococcus lactis subsp. cremoris is widely used in the manufacture of fermented
      milk products. Despite numerous attempts, efforts to isolate new strains by
      traditional plating and identification methods have not been successful.
      Previously, we described oligonucleotide probes for 16S rRNAs which could be used
      to discriminate L. lactis subsp. cremoris from related strains. These probes were
      used in colony hybridization experiments to screen large numbers of colonies
      obtained from enrichment cultures. A total of 170 strains of L. lactis were
      isolated from six milk samples, two colostrum samples, and one corn sample by
      using oligonucleotide probe 212RLa specific for the species L. lactis. Fifty-nine
      of these isolates also hybridized to L. lactis subsp. cremoris-specific probe
      68RCa, and 26 of the strains which hybridized to the L. lactis subsp. cremoris
      specific probe had the L. lactis subsp. cremoris phenotype.

PMID- 7506899
TI  - Design and application of rRNA-targeted oligonucleotide probes for the
      dissimilatory iron- and manganese-reducing bacterium Shewanella putrefaciens.
AB  - A 16S rRNA-targeted oligonucleotide probe specific for the iron (Fe3+)- and
      manganese (Mn4+)-reducing bacterium Shewanella putrefaciens was constructed and
      tested in both laboratory- and field-based hybridization experiments. The
      radioactively labeled probe was used to detect S. putrefaciens in field samples
      collected from the water column and sediments of Oneida Lake in New York and its
      major southern tributary, Chittenango Creek. S. putrefaciens was quantified by
      (i) hybridization of the probe to bulk RNA extracted from field samples and
      normalization of the S. putrefaciens-specific rRNA to total eubacterial rRNA,
      (ii) a colony-based probe hybridization assay, and (iii) a colony-based
      biochemical assay which detected the formation of iron sulfide precipitates on
      triple-sugar iron agar. The results of field applications indicated that the
      three detection methods were comparable in sensitivity for detecting S.
      putrefaciens in water column and sediment samples. S. putrefaciens rRNA was
      detected in the surficial layers of the lake and creek sediments, but the levels
      of S. putrefaciens rRNA were below the detection limits in the lake and creek
      water samples. The highest concentrations of S. putrefaciens rRNA, corresponding
      to approximately 2% of the total eubacterial rRNA, were detected in the surficial
      sediments of Chittenango Creek and at a midlake site where the Oneida Lake floor
      is covered by a high concentration of ferromanganese nodules. This finding
      supports the hypothesis that metal-reducing bacteria such as S. putrefaciens are
      important components in the overall biogeochemical cycling of iron, manganese and
      other elements in seasonally anoxic freshwater basins.

PMID- 7506900
TI  - Leukocyte colony-stimulating factors. A review of associated neutrophilic
      dermatoses and vasculitides.
AB  - BACKGROUND: Hematopoietic colony-stimulating factors are a diverse group of
      cytokines now commercially available through recombinant technology. The colony
      stimulating factors have proven utility in a wide spectrum of cytopenic states,
      and their use is now common-place. Unlike many cytokines, the colony-stimulating
      factors are usually well tolerated. We present a dramatic case of pyoderma
      gangrenosum arising during granulocyte colony-stimulating factor therapy.
      Additionally, the relevant literature regarding cutaneous complications of colony
      stimulating factor therapy is summarized. OBSERVATIONS: Including our case, two
      reported patients developed pyoderma gangrenosum while under colony-stimulating
      factor therapy. Sweet's syndrome presented in an additional three patients, and
      necrotizing vasculitis was precipitated in three others. The eruptions
      consistently developed after 1 to 2 weeks of colony-stimulating factor therapy
      and were apparently unrelated to the underlying systemic illness. Although most
      reactions developed de novo, three were superimposed on a preexisting
      inflammatory process. CONCLUSIONS: Serious cutaneous adverse effects of colony
      stimulating factors are distinctly rare but include neutrophilic dermatoses and
      necrotizing vasculitis. Upregulation of neutrophilic function and secondary
      release of cytokines may induce these complications. Early recognition and
      cessation of colony-stimulating factor therapy will limit the morbidity of these
      adverse events.

PMID- 7506901
TI  - Value of cerebrospinal fluid examination in the diagnosis of meningitis in the
      newborn.
AB  - Between 1 October 1988 and 30 September 1991 the results of all 896 cerebrospinal
      fluid examinations from 736 neonates were correlated with clinical diagnosis,
      treatment, and outcome. The prevalence of fungal or bacterial meningitis in
      babies requiring lumbar puncture was only 0.95%. Gram staining had a sensitivity
      of 68% and a positive predictive value of only 46% for the diagnosis of
      meningitis. Primary cultures directly onto agar plates had a sensitivity of 81%
      and positive predictive value of 46%. Broth enrichment cultures did not improve
      sensitivity and were frequently found to be false positive. Empirical treatment
      should not be altered unless more than a few organisms are seen on Gram staining.
      Primary cultures are adequate for the diagnosis of fungal and bacterial
      meningitis. Enrichment cultures should be performed only when the Gram stain
      and/or cell count suggests meningitis is likely. Clinicians should be aware that
      diagnostic tests performed in populations with a low prevalence of disease are
      likely to generate many false positive results and have a low positive predictive
      value.

PMID- 7506902
TI  - Rochalimaea henselae infection in acquired immunodeficiency syndrome causing
      inflammatory disease without angiomatosis or peliosis. Demonstration by
      immunocytochemistry and corroboration by DNA amplification.
AB  - Rochalimaea henselae causes bacillary angiomatosis, bacillary peliosis, and
      persistent bacteremia. Difficult to cultivate, it is detectable in infected
      tissues by immunocytochemistry. This technique demonstrated R henselae in autopsy
      specimens obtained from three deceased patients who had acquired immunodeficiency
      syndrome, with pathologic tissue changes lacking neoangiogenic features. From the
      first patient, the cause of nodular collections of lymphocytes and nonepithelioid
      histiocytes in the liver, spleen, lymph nodes, bone marrow, and heart eluded
      detection until immunocytochemical identification of R henselae. In the second
      case, unexpected gross and microscopic necroinflammatory nodules in the liver and
      spleen contained Warthin-Starry-staining bacilli identified as R henselae
      immunocytochemically. The third patient was found to have pathologic changes in
      his liver and spleen comparable with those of the second case, as well as several
      other disseminated infections. In two cases, identification of R henselae was
      corroborated through sequencing polymerase chain reaction-amplified bacterial DNA
      recovered from tissue; in one case, DNA could not be amplified, possibly because
      of postmortem degradation. Application of the immunocytochemical technique thus
      has expanded the recognized spectrum of histopathologic findings associated with
      R henselae infection in acquired immunodeficiency syndrome, as well as proving to
      be potentially more sensitive than DNA amplification for this purpose when
      applied to autopsy tissues.

PMID- 7506903
TI  - Occult congenital syphilis in macerated stillborn fetuses.
AB  - Five cases of macerated stillborn fetuses with congenital syphilis were studied.
      Despite severe maceration with visceral autolysis, spirochetes could be easily
      detected using Warthin-Starry stains. Clues that led to performing silver stains
      included the presence of an enlarged liver, spleen, chorioamnionitis, and
      nucleated red blood cells in villous capillaries. In a patient population where
      prenatal care is not always obtained, and maternal serologic tests results are
      not available at the time of delivery, these pathologic clues are very helpful in
      detecting congenital syphilis in macerated stillborn fetuses where the classic
      findings of syphilitic infection, including hydrops fetalis and plasma cell
      infiltrates, may be masked.

PMID- 7506904
TI  - Expression of the tumor marker D-galactose-beta-[1-->3]-N-acetyl-D-galactosamine
      by premalignant and malignant prostate.
AB  - Accurate and consistent discrimination of prostatic carcinomas from benign
      lesions and vice versa continues to be a vexing problem in diagnostic pathology.
      We have tested the usefulness of the tumor marker D-galactose-beta-[1-->3]-N
      acetyl-D-galactosamine in differentiating the benign from the malignant and
      premalignant lesions of the prostate. A sequential galactose oxidase technique
      (overnight incubation), followed by Schiff's reaction (15 minutes), was done on
      deparaffinized tissue sections of 65 carcinomas, 25 hyperplasias, 11 foci of
      adenosis, and 10 normal specimens. While none of the 35 benign prostates and 11
      foci of adenosis expressed D-galactose-beta-[1-->3]-N-acetyl-D-galactosamine
      (100% specificity), 62 (95.4% sensitivity) of 65 adenocarcinomas variably
      expressed the marker. We therefore propose that this simple technique may have
      potential use in routine histopathological analysis of prostatic specimens. This
      marker may also serve as the basis of assays for early detection of prostatic
      malignancies.

PMID- 7506905
TI  - Cytokine expression in the placenta. The role of interleukin 1 and interleukin 1
      receptor antagonist expression in chorioamnionitis and parturition.
AB  - Interleukin 1 (IL-1) is known to be present in placental tissue and is implicated
      as an endogenous mediator of inflammation and parturition. This study was
      undertaken to assess the role of IL-1 receptor antagonist (IL-1ra) in the
      placenta. Placentas with acute chorioamnionitis, with meconium staining, and
      without significant inflammation were examined for immunohistochemical expression
      of IL-1 and IL-1ra. Interleukin 1 and IL-1ra immunoreactivity was variably noted
      in the amnion, trophoblast, vascular smooth muscle, stromal cells, fibrinoid, and
      decidua in all placentas. Interleukin 1 immunoreactivity was less intense than IL
      1ra immunoreactivity, and both were generally more intense in acute
      chorioamnionitis. Interleukin 1 receptor antagonist was detected (approximately 5
      to 6 ng/mL) in the amniotic fluid of pregnant women at term. Colocalization of IL
      1 and IL-1ra in normal and inflamed placentas suggests that the balance between
      these proinflammatory and anti-inflammatory mediators plays a role in parturition
      as well as in the pathogenesis of acute inflammation. An increase and/or
      imbalance in the IL-1 and IL-1ra expression associated with chorioamnionitis may
      precipitate preterm labor.

PMID- 7506906
TI  - Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute
      arsenic trioxide poisoning in mice.
AB  - The therapeutic efficacy of six newly synthesized analogues of dimercaptosuccinic
      acid (DMSA) was investigated in acute arsenic trioxide poisoning in mice. Meso
      2,3-di(acetylthio)succinic acid (DATSA) and meso-2,3- di(benzoylthio)succinic
      acid (DBTSA) are analogues of DMSA with protected thiol groups ("prodrugs"), and
      DMDMS, DEDMS, DnPDMS, and DiPDMS are various di-esters of DMSA with methyl,
      ethyl, n-propyl, and isopropyl alcohols, respectively. Thirty minutes after s.c.
      injection of an LD80 of arsenic trioxide (65 mumol/kg) male NMRI mice were
      treated with a single equimolar dose (0.7 mmol/kg) of DMSA i.p. or one of the
      analogues i.p. or via gastric tube (i.g.). Control animals received arsenic
      trioxide and saline 30 min later. The survival rate was recorded for 30 days. All
      of the animals treated with DMSA i.p. survived and all controls died within 2
      days. Administered i.g., DATSA and DBTSA increased the survival rate to 29% and
      43%, and injected i.p. to 86%. Treatment with DMDMS i.p. and i.g., and with
      DEDMS, DnPDMS, and DiPDMS i.g. did not reduce lethality. Given i.p., DnPDMS
      increased the survival rate to 72%, and DEDMS and DiPDMS to 86%, respectively. To
      investigate the efficacy of the DMSA analogues in reducing the tissue content of
      arsenic, male NMRI mice received an s.c. injection of an LD5 of arsenic trioxide
      containing a tracer dose of 73-As(III) (42.5 mumol/kg body wt). Thirty minutes
      later, saline (controls) or a single equimolar dose (0.7 mmol/kg) of DMSA i.p.,
      or one of the analogues i.p. or i.g. was administered. The arsenic content of
      various organs (blood, liver, kidneys, heart, lungs, spleen, small intestine,
      large intestine, brain, testes, skeletal muscle, and skin) at 30 min, 2 h, 4 h, 6
      h, and 8 h after the arsenic injection was measured using a gamma
      counter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7506907
TI  - Effects of 60 Hz electric and magnetic fields on the development of the rat
      cerebellum.
AB  - The effects of extremely low frequency (ELF) electromagnetic (EM) fields on the
      maturation of the rat cerebellum were studied. Newborn rats were exposed to 60 Hz
      electric and magnetic fields under three different combinations in a specially
      constructed apparatus. The pups were irradiated for 7-8 h daily, with a 30-min
      interruption for nursing. Pups were kept with their mothers for the remainder of
      the time. After approximately 1, 2, or 3 weeks of exposure, the pups were killed.
      Control pups were sham exposed. The somatic growth of the irradiated rats did not
      show any significant difference from sham-exposed controls. At 1 kV/m and 10
      gauss exposure, there was a small but statistically significant decrease in
      cerebellar mass. In rats exposed at 1 kV/m and 10 gauss, DNA and RNA levels were
      significantly higher than those in sham-exposed controls at 6 and 13 days of age,
      but at 20 days, these two biochemical constituents were similar in both groups of
      rats. The ELF-EM treatment had no effect on protein and cerebroside
      concentrations. In terms of age effects, DNA and RNA exhibited increases from 6
      to 13 days of age, and declined from 13 to 20 days. Protein and cerebroside
      levels exhibited increases during the 6-20-day periods. In rats exposed at 100
      kV/m and 1 gauss, the DNA levels were initially less than those of sham-exposed
      controls at 8 days of age, reached approximately the same levels at 14 days, and
      then were higher than those of controls at 22 days. There was, therefore, a
      significant ELF-EM effect as well as a significant interaction between age and
      ELF-EM exposure. In terms of age effects, DNA levels for both control and exposed
      animals increased from 8 to 14 days. From 14 to 22 days, DNA levels of exposed
      rats continued to increase while those of the controls decreased. This age effect
      was significant. RNA levels in both groups of animals showed increases from 8 to
      14 days of age, but the increase was less for the irradiated animals than for the
      controls. From days 14 to 22, RNA levels for both groups showed a reduction, but
      the decrease was greater in the irradiated than in control rats. ELF-EM treatment
      significantly reduced protein levels at 8 days of age, but at 14 to 22 days,
      protein levels of exposed rats were higher than those of controls.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7506908
TI  - Effects of 60 Hz electric and magnetic fields on maturation of the rat
      neopallium.
AB  - This study was undertaken to determine the effects of extremely low frequency
      (ELF; 60 Hz) electromagnetic (EM) fields on somatic growth and cortical
      development, as well as biochemical and morphological maturation, of the rat
      neopallium. On the fifth day of pregnancy, female rats were put in pairs into
      plastic cages that were housed in a specially constructed apparatus for
      irradiation under three separate sets of combination and intensity: 1) 1 kV/m and
      10 gauss; 2) 100 kV/m and 1 gauss; and 3) 100 kV/m and 10 gauss. The dams were
      exposed for 23 h daily, from days 5 through 19 postconception, after which they
      were returned to cages outside the exposure apparatus until they littered. The
      neonates were culled to eight pups per litter. At 0 (birth), 5, 12, and 19 days
      postnatally, they were killed for biochemical and morphological studies. Another
      group of pregnant rats was sham-exposed in an identical apparatus, which was not
      energized, and the pups were used as controls. The irradiated rats exhibited no
      physical abnormalities, nor did they show brain deformities such as swelling or
      herniation following exposure to ELF-EM fields. There was no difference in
      somatic growth between control and exposed rats, but a small reduction in
      cortical weight was observed in rats exposed at 1 kV/m and 10 gauss, and 100 kV/m
      and 1 gauss, respectively. Biochemical measurements of DNA, RNA, protein, and
      cerebroside concentrations indicated that among the three separate exposures,
      only the neopallium of rats exposed at 1 kV/m and 10 gauss showed a small
      reduction in DNA level, as well as small reductions in RNA and protein levels. No
      changes were noticed in cerebroside levels in any exposed animals, and there were
      no differences in protein/DNA and cerebroside/DNA ratios between control and
      exposed rats. Morphological observations did not reveal any detectable
      alterations in the irradiated rats. These results indicate that exposure to ELF
      EM fields caused minimal or no changes in somatic growth and cerebral development
      of the rat.

PMID- 7506909
TI  - [Antigenic polysaccharides of bacteria 38. Structure of O-antigens of Pseudomonas
      solanacearum ICMP 7942 and ICMP 8169].
AB  - The structures I and II were established for the O-antigens of Pseudomonas
      solanacearum ICMP 7942 and ICMP 8169, respectively, by means of NMR-spectroscopy,
      including 2D homonuclear shift-correlated spectroscopy (COSY), rotating-frame NOE
      spectroscopy (ROESY) and heteronuclear 13C, 1H multiquantum correlation
      spectroscopy (HMQC). In the polysaccharide of the ICMP 8169 strain substitution
      of the main chain by the xylose residue is non-stoichiometric, i.e. this antigen
      contains also the repeating units of the polysaccharide of the ICMP 7942 strain
      (the ratio II: I is approximately 3:1). [formula: see text]

PMID- 7506911
TI  - Normal amylase levels in the presentation of acute pancreatitis.
AB  - Recent literature suggests that serum amylase levels are not an appropriate
      screen for the diagnosis of acute pancreatitis because specificity and
      sensitivity are poor. Evidence from several studies supports the use of lipase
      determinations to diagnose acute pancreatitis, and recent improvements in this
      assay have made it more readily available to the emergency physician. This
      retrospective review compares the use of serum amylase to lipase levels in the
      diagnosis of acute pancreatitis in 52 patients who presented to the emergency
      department, with the hospital discharge diagnosis serving as the gold standard to
      which the assays were compared. Serum lipase was found to be more sensitive than
      serum amylase (95% vs 79%); serum amylase levels decreased to normal
      significantly faster than lipase levels.

PMID- 7506910
TI  - [Structural study of O-specific polysaccharides from Proteus mirabilis O28 and
      3/6, containing amides of D-galacturonic acid with L-amino acids; C-methylation
      and beta-elimination at L-serine and L-threonine residues upon analysis using the
      methylation method].
AB  - Structures of the O-specific polysaccharides of Proteus mirabilis O28 and 3/6
      were studied by partial acid hydrolysis followed by borohydride reduction and
      methylation and GLC/MS analysis of the resulting glycosyl alditol derivatives. C
      Methylation and beta-elimination in serine and threonine attached to the carboxyl
      group of galacturonic acid were observed in the course of the methylation
      analysis.

PMID- 7506912
TI  - Maternal serum alpha-fetoprotein screening: the need to use race/ethnic specific
      medians in Asians.
AB  - OBJECTIVES: We questioned whether race-specific databases for maternal serum
      alpha-fetoprotein (MSAFP) screening should be added to those already available
      for African-American and white patients. STUDY DESIGN: We analyzed 138,272 MSAFP
      samples. The geographic origin of the samples was New York metropolitan area.
      Patients were classified as white, African-American, Hispanic or Asian. The usual
      adjustments were made and groups compared. Statistical analysis included ANOVA
      and multiple comparison test. RESULTS: MSAFP values are highest (p < 0.05) for
      Asians, followed by African-Americans, Hispanics, and whites, although the
      difference between Hispanic and white was not significant. CONCLUSIONS: Four
      separate databases are definable if specimen quantity is sufficient. Race/ethnic
      specific databases are more likely to yield the most accurate detection of
      abnormal MSAFP values, and therefore, fetal anomalies.

PMID- 7506913
TI  - Ultrasound-detected free-floating particles in amniotic fluid: correlation with
      maternal serum alpha-fetoprotein.
AB  - The objective of this study was to determine the rate of ultrasound-detected free
      floating particles in amniotic fluid during the early second trimester and their
      relationship with maternal serum alpha-fetoprotein (MSAFP) in patients with
      normal amniotic fluid alpha-fetoprotein (AFAFP). Ninety-eight consecutive
      patients undergoing second-trimester amniocentesis for various indications were
      prospectively studied. Before undergoing amniocentesis, each patient had a level
      II ultrasound examination and evaluation of the presence of free-floating
      particles. A subjective estimate of the particle amount and measurement of the
      size of the largest particle seen were made. Patients were stratified into three
      groups according to their MSAFP level (low, normal, high). Statistical
      significance of results was assessed by analysis of variance and multiple
      comparison procedure, and by nonparametric procedures, as appropriate. MSAFPs
      (mean +/- 1 SD) were 0.41 +/- 0.18 and 4.88 +/- 2.22 multiples of the median for
      the low and the high groups, respectively. All AFAFPs were within normal limits.
      Ninety-four percent of patients with high MSAFP had free-floating particles in
      amniotic fluid as compared to 43% in the low and normal groups (p < 0.01).
      Patients with high MSAFP had significantly greater density and size of particles.
      The presence of ultrasound-detected free-floating particles in amniotic fluid of
      normal patients during the early second trimester may preclude its use as a
      reliable indicator for fetal lung maturity, or suggest that the source of these
      particles may differ by trimester. High MSAFP is significantly correlated with
      the ultrasonographic appearance of free-floating particles, as well as with
      larger size and higher amount.

PMID- 7506914
TI  - Monoclonal anti-idiotypic antibodies that mimic the epitope on gp120 defined by
      anti-HIV-1 monoclonal antibody 0.5 beta.
AB  - OBJECTIVE: To develop effective, specific and safe anti-idiotypic antibody (Ab2)
      vaccines against HIV-1. DESIGN: Murine monoclonal Ab2 were generated against anti
      HIV-1 antibody 0.5 beta (Ab1), which binds to gp120, neutralizes HIV-1 and
      inhibits virus-induced syncytia formation. METHODS: Mice were immunized with Ab1,
      and Ab2 were produced from immunized mice by the hybridoma technique. The Ab2
      were characterized in vitro, injected into rabbits, and the anti-anti-idiotypes
      (Ab3) induced in the rabbits were analyzed for binding and antiviral reactivities
      by enzyme-linked immunosorbent assay, p24gag release and syncytia formation
      assays. RESULTS: Seven Ab2 bound to the antigen-combining site of Ab1, one of
      which (UD7) induced Ab3 in rabbits that were Ab1-like in their binding
      reactivities to PB1 (recombinant gp120 fragment) or peptides of gp120, and shared
      idiotypes with the Ab1. Crude Ab3-containing sera specifically and effectively
      neutralized the virus. CONCLUSION: Monoclonal Ab2 UD7 has potential as a vaccine
      against HIV-1.

PMID- 7506915
TI  - Depletion of Langerhans cells in cervical HPV infection is associated with
      replication of the virus.
AB  - We studied the quantity of Langerhans cells in 36 patients with cervical human
      papillomavirus (HPV) infection. Significantly fewer Langerhans cells (p < 0.05)
      were found in patients with compared to those without DNA tetraploidy. Similarly,
      patients positive for HPV 16/18 DNA by in situ hybridization or antipeptide IgA
      antibodies to HPV 18 tended to have fewer Langerhans cells than those negative
      for HPV 16/18 DNA or IgA antibodies. Our results suggest that depletion of
      Langerhans cells is associated with productive HPV 16/18 infection in the
      cervical epithelium.

PMID- 7506916
TI  - Biotyping, phage typing, and O-serotyping of clinical isolates of Enterobacter
      cloacae.
AB  - The purpose of this study was to make an independent evaluation of the methods of
      bio-, phage-, and O-serotyping which had been used only in the laboratory of
      origin, and to assess the extent of possible cross-infection of Enterobacter
      cloacae in a Danish university hospital. The material consisted of 237 clinical
      isolates of E. cloacae from the clinical microbiology laboratory at Hvidovre
      Hospital. The typability of bio-, phage-, and serotyping was 100%, 83%, and 85%,
      respectively. Reproducibility of serotyping was 90% and of phage typing 96% if
      two major differences were allowed to differentiate between patterns. O
      serotyping had the highest discriminatory power and combination of all typing
      methods further increased discrimination. Outbreaks of E. cloacae were not
      evident in clinical departments, but cross-infections from one department to
      another could not be completely ruled out. We concluded that the combination of
      bio-, phage- and O-serotyping is sufficiently discriminating and will be
      satisfactory in the majority of clinical situations.

PMID- 7506917
TI  - A case of Whipple's disease presenting as supraclavicular lymphadenopathy. A case
      report.
AB  - A case of Whipple's disease occurring in a 63-year-old woman is reported.
      Cervical lymphadenopathy and vague constitutional symptoms were soon followed by
      diarrhea and weight loss. Supraclavicular lymph node exeresis suggested the
      initial diagnosis, which was confirmed by intestinal biopsy. The concurrence of
      cystic spaces, PAS-positive foamy histiocytes and epithelioid granulomas is
      considered by the authors to provide a useful histological clue in the diagnosis
      of lymph node involvement in Whipple's disease. Pathologists must be aware of
      such an un-conventional presentation of this rare entity and therefore include it
      within the differential diagnosis of cervical and/or axillary lymphadenopathies.

PMID- 7506918
TI  - Ribotyping of selected isolates of Enterobacter cloacae and clinical data related
      to biotype, phage type, O-serotype, and ribotype.
AB  - In order to evaluate if ribotyping of selected isolates of Enterobacter cloacae
      could further elucidate the epidemiology, we performed ribotyping of 109 isolates
      indistinguishable by bio-, phage-, and O-serotyping, with inconclusive typing
      results, or from patients with more than one isolate. Ribotyping provided
      additional information, and some cases of cross-infection or common source of
      infection were revealed. Under the supposition that isolates sharing the same
      ribotype were of the same origin, problems arose with respect to bio-, O-sero, as
      well as phage typing; in particular a remarkable number of isolates showed
      differences in phage type. In order to identify possible virulence
      characteristics of certain types, clinical data were related to bio-, phage-, O
      sero-, and ribotype. Biotype 66 was significantly more frequent among blood
      culture isolates (P = 0.001), but this might have reflected the presence of a
      certain strain in the environment of the intensive care unit, where patients were
      more likely to develop bacteraemia; serotype 04 was significantly more frequent
      among isolates from the urinary tract (P = 0.02), and serotype 013 was more
      frequent among women (P = 0.05). One ribotype was found only among community
      acquired isolates, which might suggest that it is a frequent but less virulent
      strain.

PMID- 7506920
TI  - Substance P-immunoreactive neurons of the bovine forestomach mucosa: their
      presumptive role in a sensory mechanism.
AB  - Substance P-immunoreactive nerve fibers and cell bodies were examined in the
      forestomach mucosa of the calf and cow pretreated with colchicine, using thick
      (100 microns) floating sections. Intraepithelial nerve fibers were identified,
      appearing only rarely in the rumen and reticulum, and completely absent from the
      omasum. Nerve fibers were observed in the lamina propria of all the regions of
      the forestomach examined. A few thin nerve fibers were seen in the core of the
      ruminal papillae of the calf, whereas in the cow they appeared very coarse in
      nature. Flocculent and complicated nerve fiber networks were seen in the
      connective tissue of the reticular papillae. Mucosal nerve fibers formed a
      peculiar glomerulus-like architecture in the omasal papillae of the calf, while
      in the cow, the nerve fibers were largely restricted in distribution to the
      vicinity of the epithelium within the connective tissue pegs. Immunoreactive
      nerve cell bodies were found in the ruminal atrium, the dorsal sac and the
      ventral sac of the rumen of the calf and in the reticulum of both the calf and
      cow. Some of these neurons exhibited processes that appeared to course toward the
      papillae. In total, substance P-immunoreactive nerve fibers and cell bodies were
      more abundant in the calf than in the cow. These distributions demonstrate that
      the neural circuitry of the bovine forestomach contains substance P
      immunoreactivity in the mucosa as well as in the muscle layer, pointing to its
      possible importance in the regulation of the forestomach function. Substance P
      immunoreactive nerve fibers were numerous in the reticular papillae of the calf
      and cow and in the omasal papillae of the calf. The positive fibers at these
      localities may act as mucosal receptors.

PMID- 7506919
TI  - Rapid analysis of rearranged kappa light chain genes of circulating
      polysaccharide-specific B lymphocytes by means of immunomagnetic beads and the
      polymerase chain reaction.
AB  - Analysis of rearranged immunoglobulin genes used by B lymphocytes of known
      specificity is an important tool for the study of diversity and selection of B
      lymphocytes. Usually hybridoma cell lines are used for such analyses, but they
      are difficult to obtain from humans and may not be representative of the B
      lymphocytes activated in vivo. Here, we present a method for rapid analysis of
      the rearranged kappa light chain genes used by human circulating antigen-specific
      B lymphocytes. After vaccination with Haemophilus influenzae type b capsular
      polysaccharide (HibCP) conjugated with protein, the HibCP-specific B lymphocytes
      were isolated by antigen-coated immunomagnetic beads. After the purification, at
      least 98% of the immunoglobulin-secreting recovered cells were HibCP specific.
      The RNA was isolated and amplified by cDNA synthesis using a kappa constant
      region primer followed by polymerase chain reaction (PCR) using in addition a
      degenerate kappa light chain signal peptide region primer. The PCR product was
      cloned into the M13mp18 phage. The cloning efficiency was 100-600 clones/ml of
      blood. Of the 86 clones sequenced, 90% represented rearranged kappa light chain
      genes from different antibody-secreting cells. Examples of rearranged kappa genes
      used by HibCP-specific antibody-secreting cells from 4 adult vaccinees are given,
      representing the 3 largest of the 4 kappa variable region families. This method
      is a new tool for the investigation of vaccine-induced antibody responses with
      special reference to immunoglobulin gene usage and variability.

PMID- 7506921
TI  - The long-term neurodevelopmental outcome for very low birthweight (VLBW) infants
      with 'dystonic' signs at 4 months of age.
AB  - As very low birthweight (VLBW) infants are at a high risk of developmental
      handicap, it is important to establish predictors of long-term adverse outcome at
      an early age so that early intervention can be instituted. Longitudinal
      neurodevelopmental assessments were performed in 107 VLBW infants at 1, 4, 8 and
      12 months corrected age. Eighteen were diagnosed as 'dystonic' at 4 months of
      age. This study compared the outcomes at 4 and 6 years for 15 of the 18 dystonic
      with 75 of the 89 non-dystonic VLBW infants, respectively. At 9 years of age,
      nine dystonic and 54 non-dystonic infants were assessed on the Rutter Behaviour
      Questionnaire. Dystonic children had a lower mean General Cognitive Index (GCI; P
      = 0.001) and a higher incidence of disability as measured by the Burns Neuro
      Sensori-Motor Developmental Assessment Scale (P = 0.0005) and Kitchen disability
      grading (P = 0.001). Even if the minor neurological aberrations of the premature
      dystonia syndrome in VLBW infants abate by one year of life, these infants still
      constitute a high-risk group for subsequent neurodevelopmental disability and
      therefore require close observation and probably early intervention.

PMID- 7506923
TI  - Matrix metalloproteinase 9 expression in primary human prostatic adenocarcinoma
      and benign prostatic hyperplasia.
AB  - Matrix metalloproteinase (MMP) expression was investigated in patients with
      prostatic adenocarcinoma and benign prostatic hyperplasia (BPH). Forty-one men
      were studied: 26 had histologically proven prostate cancer, with 14 (54%) showing
      metastatic disease; 15 patients had BPH. Prostatic tissue was obtained from
      transurethral resection and needle core biopsies; gelatinolytic activity was
      determined by zymography. Seven gelatinolytic bands were detected, with molecular
      weights ranging from > 100 kilodalton (kDa) to 29 kDa. Nine of 14 patients (64%)
      with skeletal metastases had 92 kDa activity, present in only two of 12 patients
      (17%) with a negative bone scan, and absent in BPH. The 92 kDa gelatinolytic
      activity was expressed in 73% of aneuploid tumours compared with 20% of diploid
      tumours. A 97 kDa gelatinase was expressed in 80% of BPH samples and 23% of
      carcinoma patients. Enzyme bands of 72, 66 and 45 kDa were equally expressed in
      malignant tissue, irrespective of metastatic status, but were expressed in fewer
      BPH patients. The 97, 92, 66 and 45 kDa enzymes were identified as being pro-MMP
      9 sequences by Western blotting, using a specific antibody directed against the
      pro sequence of the mature protein. MMP activity appeared to be increased in
      malignant prostatic tissue compared with BPH. Pro-MMP-9, in its 92 kDa form, was
      shown to be exclusively expressed by malignant prostatic tissue, and in
      particular by tumours that exhibited the aggressive and metastatic phenotype.

PMID- 7506922
TI  - Constitutive production of multiple colony-stimulating factors in patients with
      lung cancer associated with neutrophilia.
AB  - Production of colony-stimulating factor (CSF) was examined in three patients with
      lung cancer associated with neutrophilia. All three patients presented a marked
      increase in neutrophil count (26,000-39,000 microliters-1) that continued at
      least for 3 weeks and rapidly disappeared after surgical removal of the tumours.
      Culture media (CM) incubated with the excised tumour tissues stimulated the
      colony formation of bone marrow myeloid progenitor cells in vitro. Northern blot
      analysis of poly(A)+ RNA from the tumour tissues revealed a constitutive
      expression of granulocyte (G), macrophage (M), and granulocyte-macrophage (GM)
      CSF genes in all tumours. Immunoassay specific for these CSFs revealed that G-
      and M-CSF immunoreactivity was detected in all CM and GM-CSF protein in two out
      of three CM. The plasma CSF levels also increased before operation and decreased
      to normal or near-normal range after operation. In contrast, tumour cell CM
      obtained from two lung cancer patients without leucocytosis neither stimulated
      haematopoietic colony formation nor contained immunoreactive CSFs. These results
      indicated that the neutrophilia found in the three patients was probably caused
      by constitutive production of multiple CSFs by lung cancer cells.

PMID- 7506924
TI  - Problems with p53 immunohistochemical staining: the effect of fixation and
      variation in the methods of evaluation.
AB  - The availability of antibodies which recognise p53 protein in paraffin-embedded
      tissue has created the opportunity to use immunohistochemistry to study the
      expression of p53 in a wide variety of clinical material. In this paper we have
      investigated the relationship between the type of fixative and the pattern of p53
      staining in mammary carcinoma. Optimal results were obtained from breast tissue
      fixed in phenol formol saline, methacarn or cold formol saline with positive
      staining for stabilised p53 protein occurring in 69/95 (73%) cases studied. Care
      must be taken in the interpretation of these results since positive staining for
      p53 protein is not always indicative of mutation of the p53 gene. Furthermore, a
      range of staining patterns is seen in mammary carcinomas, making interpretation
      difficult. Assessment of staining needs to be standardised in order that
      different studies can be compared. However, in breast carcinoma, p53
      immunohistochemistry appears to give information relating to tumour grade and,
      independently, to prognosis.

PMID- 7506926
TI  - HLA and ICAM-1 expression in alopecia areata in vivo and in vitro: the role of
      cytokines.
AB  - To investigate the hypothesis that aberrant HLA and adhesion molecule expression
      in alopecia areata (AA) are secondary to local release of interferon-gamma (IFN
      gamma) or other cytokines, we have studied HLA ABC, -DQ, -DR and ICAM-1
      expression by immunohistochemistry, and compared patterns of expression in
      lesional tissue sections with those observed in hair follicles maintained in
      short-term organ culture, both from normal individuals and non-lesional sites in
      AA patients. The organ cultures were supplemented with IFN-gamma, tumour necrosis
      factor-alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor
      (GM-CSF), in a range of doses. In lesional AA tissue sections, there was close
      spatial correlation of ICAM-1 with HLA-DR; prominent staining being noted in the
      pre-cortical matrix and dermal papilla (DP) of lesional anagen follicles. In
      cultured follicles, dose-dependent induction of HLA class I, DR and ICAM-1 by IFN
      gamma, and HLA class I and ICAM-1, but not HLA-DR, by TNF-alpha was observed in
      follicular epithelium, mainly in the outer root sheath (ORS). The findings in
      these cultures were the same in follicles derived from normal individuals and AA
      patients. Cytokine-induced patterns of HLA and ICAM-1 expression observed in
      vitro in cultured follicles differed significantly from those observed in vivo in
      lesional tissue sections. In particular, IFN-gamma failed to induce HLA-DR
      expression in the pre-cortical matrix and dermal papilla (DP), sites where this
      is usually observed in AA. The results suggest local cytokine release is not the
      sole determinant of aberrant HLA-DR expression in AA.

PMID- 7506927
TI  - Low-dose ultraviolet-B irradiation depletes human epidermal Langerhans cells.
AB  - We have examined the effects of low-dose monochromatic UVB irradiation (295 +/- 5
      nm), biologically equivalent to that generally incident on the skin during a 12
      session sun-bed course, on the expression of the CD1a epidermal Langerhans cell
      surface marker in human skin in vivo. In five subjects, 1.5 minimal erythema
      doses (MEDs) at 295 nm depleted its expression by 50%. In five further subjects,
      a single 1.5 MED dose, 1.5 MEDs in 10 equal fractions on alternate days, and a
      single 1.5 MED dose at one-tenth the previously used irradiance, delivered to
      separate sites, also led to variable but significant depletion of CD1a expression
      of around 30-50%. Thus, low-dose UVB irradiation, whether received rapidly or
      slowly, appears significantly and approximately equally to deplete human
      epidermal Langerhans cell numbers as measured by CD1a expression.

PMID- 7506925
TI  - Immunotoxins recognising a new epitope on the neural cell adhesion molecule have
      potent cytotoxic effects against small cell lung cancer.
AB  - The present study describes a comparison of two potent immunotoxins which utilise
      an identical targeting component, a monoclonal antibody (SEN7) specific for small
      cell lung cancer (SCLC), conjugated to two different effector components, blocked
      ricin (bR) and Pseudomonas exotoxin A (PE). SEN7 recognises a novel epitope on
      the neural cell adhesion molecule (NCAM) which is highly associated with SCLC.
      The immunotoxins SEN7-PE and SEN7-bR were selectively and potently active against
      a number of SCLC cell lines, of both classic and variant morphologies, inhibiting
      the incorporation of [3H]leucine with IC50 values ranging between 22 pM and 85 pM
      and between 7 pM and 62 pM for SEN7-PE and SEN7-bR respectively. Intoxication by
      both immunotoxins proceeded rapidly following short 2 h lag phases; the initial
      rates of protein synthesis inhibition occurred with t50 values of 6.5 h for SEN7
      PE and 5.5 h for SEN7-bR. Monensin drastically enhanced the cytotoxic activity of
      the weakly active SEN7-ricin A-chain by 2,100-fold and of SEN7-bR by 80-fold but
      had no effect on SEN7-PE. In limiting dilution assays, four and more than 4.5
      logs of clonogenic SW2 tumour cells were selectively eliminated from the cultures
      during continuous exposure to the immunotoxins SEN7-PE and SEN7-bR respectively,
      while antigen-negative cells required up to 1,000-fold more drug for a similar
      cell kill. SW2 cells surviving SEN7-bR treatment in the cultures did not express
      NCAM and consequently were not selectively killed by SEN7 immunotoxins. SW2 cells
      surviving continuous exposure to SEN7-PE showed no alteration in NCAM expression
      but were more resistant to intoxication mediated by PE. These cells were still
      sensitive to SEN7-bR.

PMID- 7506928
TI  - Lipopolysaccharides of Campylobacter jejuni serotype O:19: structures of O
      antigen chains from the serostrain and two bacterial isolates from patients with
      the Guillain-Barre syndrome.
AB  - An O antigenic polysaccharide was liberated from the lipopolysaccharide of high
      M(r) from Campylobacter jejuni serotype O:19 by acetic acid hydrolysis of the
      ketosidic linkage to lipid A. The structure of the polysaccharide was established
      in several one- and two-dimensional 1H and 13C NMR experiments, fast atom
      bombardment mass spectrometry and methylation linkage analysis of the
      permethylated glycan and its degradation products. It is concluded that the
      glycan is a derivative of hyaluronic acid in which the beta-D-glucuronic acid
      residues in the alternating sequence [-4)-beta-D-GlcA-(1-->3)-beta-D-GlcNAc-(1]n
      are present as amides of 2-amino-2-deoxyglycerol. Parallel experiments were
      performed on O antigens liberated from lipopolysaccharides of high M(r) from
      bacterial isolates that had been obtained from two patients who subsequently
      developed the Guillain-Barre syndrome. Within the limits of structural analysis
      by NMR spectroscopy and methylation linkage analysis, both these O antigens were
      identical to that from the serostrain.

PMID- 7506929
TI  - Rotational mobility of the fibrinogen receptor glycoprotein IIb/IIIa or integrin
      alpha IIb beta 3 in the plasma membrane of human platelets.
AB  - Integrin alpha IIb beta 3 or glycoprotein IIb/IIIa (GPIIb/IIIa, 228 kDa) is a
      Ca(2+)-dependent, noncovalent heterodimer of glycoproteins IIb (GPIIb or alpha
      IIb, 136 kDa) and IIIa (GPIIIa or beta 3, 92 kDa), which serves as the receptor
      for fibrinogen and other adhesive proteins at the surface of activated platelets.
      We have determined the microsecond-range rotational motions of alpha IIb beta 3
      in resting platelets, in isolated plasma membranes, and reconstituted in 1
      palmitoyl-2-oleoylphosphatidylcholine (POPC) bilayers. The measurements were
      based on the time-resolved phosphorescence anisotropy [r(t)] of erythrosin
      labeled F(ab) fragments [Er-F(ab)] of monoclonal antibodies bound to alpha IIb
      beta 3. In general, the r(t) decays were satisfactorily fitted to the sum of the
      two exponential terms and a constant, from which the initial anisotropy (r(in)
      approximately 0.05-0.11), the short (phi 1 approximately 1-14 microseconds) and
      the long (phi 2 approximately 15-60 microseconds) rotational correlation times,
      and the limiting anisotropy (r infinity approximately 0.02-0.07) were obtained.
      The observed values depended on the platelet preparation, temperature, Ca2+
      concentration, and the antibody used. In accordance with data on the order
      parameter and the viscosity of the lipid bilayer of the platelet plasma membrane,
      phi 2 and r infinity of the alpha IIb beta 3-Er-F(ab) complexes in the three
      preparations decreased with the increase of temperature, the r(t) curves being
      fully reversible within the interval from 5 to 35 degrees C.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7506930
TI  - Pf3 coat protein forms voltage-gated ion channels in planar lipid bilayers.
AB  - The coat protein of bacteriophage Pf3 forms discrete and stable ion channels of
      uniform size in planar bilayers of asolectin. Its primary sequence suggests a
      channel formed by a bundle of transmembrane helices. Since the apparent
      transmembrane region only consists of strongly hydrophobic residues, it
      represents a new class of channel-forming proteins. The channel activity is
      strongly voltage-dependent. The single-channel conductance of 60 pS (at 100 mV)
      in 0.2 M NaCl is slightly voltage-dependent, indicating conformational changes of
      the pore upon variation of the transmembrane electric field. The channel is
      unselective which suggests that the pore is of aqueous character. For the
      observed conductance, a channel diameter of 3.6 A is consistent with a tetrameric
      alpha-helix bundle, as calculated from a barrel-stave model. A pronounced
      dependence of the gating kinetics with increasing voltage arises from two
      opposing effects: an increase in the number of open channel structures, and a
      simultaneous, more than 3-fold decrease in the channel lifetime. Thus, a maximum
      activity is reached around 100 mV, a range which corresponds well with
      physiological membrane potentials. The channels activate only upon application of
      a positive voltage on the side of the membrane to which the protein had been
      added. The slow relaxation of the mean current upon application of sudden voltage
      jumps indicates a strong activation barrier in the channel gating process, which
      may result from the membrane translocation of the charged residues of the peptide
      ends. A channel-mediated import mechanism is suggested for the bacterial
      infection by phage DNA.

PMID- 7506931
TI  - Fragmentation of phospholipid bilayers by myelin basic protein.
AB  - Human myelin basic protein (MBP) is shown to disrupt multilamellar
      phosphatidylcholine bilayers into small lipoprotein particles in a manner similar
      to the cytolytic peptide melittin (Dufourc, E. J., Smith, I. C. P., & Dufourcq,
      J. (1986) Biochemistry 25, 6448-6455). This bilayer fragmentation, as monitored
      by 31P nuclear magnetic resonance, is temperature-dependent and completely
      inhibited by the presence of small amounts of negatively charged
      phosphatidylserine. The stabilizing property of phosphatidylserine is lost with
      the neutralization of its negative charges upon membrane binding of cationic
      species such as calcium ions. No MBP-induced fragmentation is observed with
      bilayers of negative or zwitterionic lipid mixtures which mimic the myelin lipid
      composition. The membrane fragmentation observed in vitro in the presence of MBP
      could play a role in vivo in demyelinating diseases.

PMID- 7506932
TI  - RNA displacement pathways during transcription from synthetic RNA-DNA bubble
      duplexes.
AB  - Previously [Daube, S.S., & von Hippel, P.H. (1992) Science 258, 1320] we have
      shown that functional transcription elongation complexes can be formed by adding
      ribonucleotide triphosphates, Mg2+, and either Escherichia coli or T7 RNA
      polymerase to synthetic RNA-DNA bubble-duplex constructs. Here these observations
      are extended to show that the RNA transcripts synthesized from these bubble
      duplex constructs are properly displaced from the DNA template during
      transcription. Some details of the displacement process differ between the
      polymerases tested. Thus the transcript is fully and processively displaced in
      the course of T7 polymerase-catalyzed synthesis from the bubble-duplex
      constructs, while the presence of a large excess of an RNA (or DNA) oligomer
      complementary to the DNA template sequence within the "permanent" DNA bubble is
      required to attain complete displacement of the nascent RNA from the construct
      during synthesis with the core E. coli enzyme. In addition, a correlation is
      shown between proper RNA displacement and the achievement of full-length
      transcript synthesis. We conclude that both the T7 polymerase and the E. coli
      core enzyme actively displace the nascent transcript during elongation and that
      the requirement for an RNA trap with the E. coli enzyme reflects its slower rate
      of synthesis. This suggests that these experiments may provide insight into the
      relative rates of transcript elongation and secondary structure formation within
      the nascent RNA in elongation and termination. By use of the RNA oligomer trap
      methodology, multiple rounds of transcript synthesis should be achievable on
      these bubble-duplex constructs with any polymerase.

PMID- 7506933
TI  - Intimations of K+ channel structure from a complete functional map of the
      molecular surface of charybdotoxin.
AB  - The external vestibules of many K+ channels carry a high-affinity receptor for
      charybdotoxin, a peptide of known structure. Point mutations of a recombinant
      toxin identified the residues directly involved in the interaction with a Ca(2+)
      activated K+ channel. The interaction surface is formed from 8 of the 37 residues
      and covers about 25% of the peptide's molecular surface. The shape of the toxin
      permits a deduced picture of the complementary receptor site in the external
      vestibule of the K+ channel.

PMID- 7506934
TI  - The FAR domain defines a new Xenopus laevis zinc finger protein subfamily with
      specific RNA homopolymer binding activity.
AB  - The zinc finger motif defines a large superfamily of nucleic acid binding
      proteins. Conserved amino acid sequence elements associated with structurally
      variant zinc finger clusters define subfamilies of zinc finger proteins (ZFPs).
      The FAR domain (Finger Associated Repeats) is a novel type of repeat element
      found at the amino-terminus in a subfamily of Xenopus laevis ZFPs. Northern blot
      analyses of three different members of the FAR subfamily (XFO 6, XFO 9-3 and XFG
      68) revealed that each of these genes is transcribed during oogenesis,
      embryogenesis and in all investigated tissues of adult animals thereby indicating
      a ubiquitous distribution of transcripts. All FAR-ZFPs tested so far have
      specific RNA homopolymer binding activity; they associate preferentially with
      poly(U). The FAR repeats possess limited primary sequence homology with a
      sequence in the nucleolar shuttling protein NO38, within a region that contains a
      casein kinase II phosphorylation site.

PMID- 7506935
TI  - Hematopoietic receptors of class III receptor-type tyrosine kinases.
AB  - Receptor-type tyrosine kinases (RTKs) constitute a family of proteins involved in
      growth and developmental processes. Class III RTKs are characterized by an
      extracellular region composed of five immunoglobulin-like domains and by a split
      tyrosine kinase domain. Some of the class III RTKs perform major functions in
      hematopoiesis and are the focus of this review. They are the colony-stimulating
      factor-1 (CSF1) and Steel factor (SLF) receptors, encoded by the FMS and KIT
      protooncogenes, respectively, and the product of the FLT3/FLK2 gene. The
      structural, biochemical, functional, and pathological features of these three
      receptors and genes are reviewed.

PMID- 7506936
TI  - Serological relationships and epitope profiles of isolates of okra leaf curl
      geminivirus from Africa and the Middle East.
AB  - A panel of seven murine monoclonal antibodies (mAbs) was raised against particles
      of okra leaf curl virus (OLCV), a whitefly-transmitted geminivirus which is
      prevalent in West Africa. The mAbs detected at least six distinguishable
      epitopes, two continuous and four discontinuous. In tests with these mAbs,
      relatively little antigenic variation was found among 24 OLCV isolates from
      Burkina Faso, Chad, Ghana, Ivory Coast, Nigeria, Oman and Saudi Arabia, each
      virus isolate reacting with at least five of them. However, on the basis of their
      reactions with 17 mAbs raised against particles of a group A isolate of African
      cassava mosaic virus (ACMV), the OLCV isolates could be assigned to two groups,
      which have geographical distributions that overlap in West Africa. A network of
      antigenic relationships was revealed by reactions between the OLCV mAbs and other
      whitefly-transmitted geminiviruses from six plant species in 12 countries. OLCV
      shared the most epitopes with tobacco leaf curl (African isolates) virus, ACMV,
      Indian cassava mosaic virus and bean golden mosaic virus. Selected OLCV mAbs are
      suitable for routine detection of OLCV, and a panel of three mAbs can be used to
      identify it.

PMID- 7506937
TI  - Tobacco mosaic virus: a model antigen to study virus-antibody interactions.
AB  - For more than 50 years, tobacco mosaic virus (TMV) has been used as a model
      system for studying various aspects of virus-antibody interactions. Distinct
      epitopes called neotopes and cryptotopes have been identified in intact TMV
      particles and dissociated viral protein respectively and a correlation has been
      found to exist between the location of continuous epitopes and the extent of
      segmental mobility along the viral polypeptide chain. The occurrence of bivalent
      antibody binding was shown to influence the observed affinity of TMV antibodies
      and kinetic measurements of antibody binding to viral peptides made it possible
      to analyze the mechanism of binding of monoclonal antibodies. It seems likely
      that the TMV model will continue to yield a rich harvest of immunochemical data
      relevant to many viral systems.

PMID- 7506938
TI  - Replication of satellite RNA in vitro by homologous and heterologous cucumoviral
      RNA-dependent RNA polymerases.
AB  - The RNA-dependent RNA polymerases (RdRp) of cucumber mosaic virus (CMV) and
      peanut stunt virus (PSV), members of the cucumovirus group, have been purified
      from virus infected plants and were used to study RNA synthesis in vitro using
      different viral RNAs, two cucumoviral satellites, and chimeric satellite cDNA
      clone transcripts as templates. The results show that solubilized RdRp
      preparations of CMV and PSV have a high degree of template dependency and
      catalyze (-) strand synthesis of the homologous cucumoviral RNAs with greater
      efficiency than the RNAs of heterologous cucumoviruses, although the PSV RdRp
      exhibits a lesser specificity than the CMV RdRp. On the other hand, both (-) and
      (+) strands of the satellite RNAs of CMV and PSV are synthesized by their
      homologous but not by the heterologous viral RdRps, indicating that recognition
      of satellites by the viral RdRp determines their replicative dependence upon
      specific helper viruses. Cucumoviral RdRp reactions using chimeric satellite
      transcripts suggest that the promoter structure for the satellite (-) strand
      synthesis resides in regions harboring the 3' termini of the two satellites.

PMID- 7506939
TI  - Polymeric N-acetyl-D-glucosamine (chitin) induces histionic activation in dogs.
AB  - Analyses on the effects of polymeric N-acetyl-D-glucosamine (chitin), which was
      obtained from squid pen, on histiogenic activation in dogs were carried out with
      subcutaneous implants (5 x 5 cm2) of polyester non-woven fabric (NWF)
      supplemented with chitin (chitin group) and NWF (control group). These materials
      were implanted at 4 sites, on the lumbodorsal and lumbosacral subcutaneous
      tissues on both sides of the midline in each dog under general anesthesia. The
      implants and their surrounding tissues were isolated on post-implantation days
      (PIDs) 2, 4, 8, and 18 under general anesthesia. In the chitin group, the implant
      was organized gradually and its organization was completed on PID 18, when
      obvious angiogenesis toward the NWF was observed. On the other hand, in the
      control group, obvious angiogenesis toward the NWF was not observed
      macroscopically. Numbers of mononuclear (MN) and polymorphonuclear (PMN) cells
      concentrated around the implants on PID 2 were larger in the chitin than control
      group. In the chitin group, formation of granulating tissue around the implant
      was indicated on PID 4, whereas such a phenomenon was not observed in the control
      group. From these results, chitin accelerates the migration of MN and PMN cells
      to the NWF site with rapid follow-up organization of the NWF accompanied by
      angiogenesis.

PMID- 7506940
TI  - Digestive enzyme development in newborn piglets born of sows immunized against
      somatostatin and/or receiving growth hormone-releasing factor during gestation.
AB  - Thirty-eight second parity sows were either immunized (IMM) against somatostatin
      (SRIF) and/or injected with growth hormone-releasing factor (GRF) during
      gestation. Treatment effects on pancreatic, gastric and duodenal development as
      well as on digestive enzyme activity of piglets at birth (before suckling) or at
      24 h postpartum were investigated. Birth weights of piglets were similar across
      treatments (p > 0.1). Weight, DNA, RNA, total protein content and enzyme activity
      for all three organs increased between birth and 24 h postpartum (p < 0.01),
      except for pancreatic RNA and chymotrypsin which decreased (p < 0.01), and
      protein content of the pancreas which was unaltered (p > 0.1). Gastric RNA,
      pancreatic weight:DNA, RNA:DNA and amylase:DNA ratios were increased in 1-day-old
      piglets from SRIF-IMM sows (p < or = 0.05). GRF only had significant effects (p <
      0.05) on the maltase:DNA ratio, which it decreased. Yet, there were tendencies (p
      < 0.1) for duodenal weight, DNA and total protein content to be increased in
      piglets from GRF-injected dams. It is therefore apparent that major developmental
      changes of the pancreas, stomach and duodenum of piglets take place during the
      first 24 h postpartum. Injections of GRF and/or immunization against SRIF during
      gestation in swine also have several effects on digestive enzyme activity of
      neonatal pigs. Yet, the physiological implications of these early changes are not
      clear at the present time.

PMID- 7506941
TI  - Vascular development and heparin-binding growth factors in the bovine corpus
      luteum at several stages of the estrous cycle.
AB  - Immunolocalization of factor VIII (a specific endothelial cell marker) and
      heparin-binding (fibroblast) growth factors (HBGF)-1 and HBGF-2, along with
      quantitative image analysis, were used to evaluate vascular development and
      distribution of HBGF in the bovine corpus luteum (CL) at three stages (early,
      middle, and late) of the estrous cycle. Luteal vascularity increased from the
      early to the middle stage and then declined to the late stage. During the early
      stage, most of the microvessels were present in the cores of the tissue
      infoldings (presumably thecal-derived areas), but numerous capillary sprouts
      could be seen invading the parenchymal areas. During the middle stage, capillary
      density was so great that most parenchymal cells were in contact with one or more
      capillaries. At the late stage, relatively few capillaries were present in the
      parenchymal areas, whereas larger microvessels were prominent throughout the CL.
      Throughout the estrous cycle, HBGF-1 and HBGF-2 were present primarily in the
      cytoplasm of large and small luteal cells. For each stage of the estrous cycle,
      HBGF-2 staining was greater than that of HBGF-1. Relatively high levels of HBGF
      2, but not HBGF-1, were also present in connective tissue tracts. In addition,
      HBGF-1 and HBGF-2 appeared to co-localize in some luteal cells. Although the
      distribution of HBGF-1 was homogeneous throughout the CI, that of HBGF-2 was
      heterogeneous. For HBGF-1, staining increased from the early to the middle stage
      but remained unchanged from the middle to the late stage. In contrast, HBGF-2
      staining was greatest in the middle stage and similar in the early and late
      stages. These data are the first report of HBGF-1 and HBGF-2 immunolocalization
      in bovine luteal tissues throughout the estrous cycle, and demonstrate that HBGF
      2 staining follows a pattern similar to that of luteal vascular development.

PMID- 7506942
TI  - Estrogen regulation and localization of galanin gene expression in the rat
      uterus.
AB  - To determine whether galanin is a target for estrogenic regulation in the rat
      uterus, we measured the effects of estrogen on galanin mRNA expression in the
      uterus of ovariectomized rats and compared the results with the regulation of
      galanin in the anterior pituitary. Treatment of the animals with a single dose of
      17 beta-estradiol resulted in a rapid transient increase of galanin mRNA, similar
      to that in the pituitary of the same animals, with a peak at 3 h after
      stimulation and a return to prestimulation levels after 24 h. No galanin mRNA was
      detected in ovariectomized control animals in either tissue. By in situ
      hybridization of rat uterus 3 h after estrogen stimulation, we found that galanin
      mRNA was localized in the endometrium in stromal cells that are close to the
      lumen. There was no hybridization in the myometrium of the estrogen-treated
      animals. Surprisingly, and strikingly different from results in the pituitary, in
      the uterus with a constant and prolonged exposure to estrogen by
      diethylstilbestrol (DES) implants, the induction of galanin mRNA was only
      transient, with return to baseline levels by 24 h despite the continued presence
      of DES. On the other hand, in the pituitary there was a rapid and sustained
      increase of galanin mRNA. These data demonstrate that 1) one of the initial steps
      in the mechanism of estrogen stimulation in the rat uterus involves galanin gene
      expression; 2) in the uterus galanin mRNA is expressed in stromal cells of the
      endometrium; and 3) the regulation of galanin mRNA expression by estrogen in the
      pituitary and the uterus is markedly different.

PMID- 7506943
TI  - Antibody response of ewes and does to chimeric sheep-goat pregnancy.
AB  - Antibody production was evaluated in 62 recipients of blastomere-aggregation
      sheep-goat embryos, including 23 multiparous ewes, 21 multiparous does, 16
      primiparous does, and 2 virgin does. The reactivity of sera collected weekly
      after the embryo transfer surgery was compared to that of sera collected prior to
      the embryo transfer by means of 1) complement-dependent cytotoxicity tests
      against peripheral blood lymphocytes (PBLs) from the parents of the embryo(s) and
      from random-bred sheep and goats, 2) hemagglutination and hemolytic assays with
      red blood cells (RBCs) from the two sires of the embryo(s), and 3) assays with
      PBLs and RBCs following absorptions with RBCs and PBLs from the parents and
      offspring. Although cross-reactivity to ovine and caprine PBL antigens was
      present in the control sera of some recipients, xenogeneic immunization during
      pregnancy was detected in 20 of 30 recipients that experienced term pregnancy.
      The xenogeneic response involved the production of antibody that reacted with
      both PBLs and RBCs. Allogeneic responses to RBCs were not observed, but
      allogeneic responses to PBLs occurred frequently, beginning after the onset of
      the xenogeneic response in most recipients (98 +/- 28 vs. 57 +/- 15 days in ewes;
      93 +/- 23 vs. 46 +/- 7 days in does; mean day of onset +/- SD). The onsets of the
      responses were examined in conjunction with data collected on fetal and placental
      chimerism to evaluate possible routes of immunization. The onsets of the
      allogeneic responses and the limited serum reactivity to third-party PBLs
      suggested that fetal lymphocytes leaking across the placenta immunized the
      recipients to parentally inherited polymorphic antigens. The xenogeneic responses
      were associated with placental chimerism and appeared to involve the recognition
      of a species-specific monomorphic antigen shared by PBLs and RBCs. Neither of the
      responses appeared to affect continuation of pregnancy to term.

PMID- 7506944
TI  - Cellular and ionic signal transduction mechanisms for the mechanical activation
      of renal arterial vascular smooth muscle.
AB  - Elevations in transmural pressure increase active vascular tone in arteries from
      most vascular beds, and this myogenic response has been shown to play an
      important role in the regulation of blood flow in the kidney and other organs.
      The myogenic response in isolated perfused arteries is associated with
      depolarization of vascular smooth muscle cells and a rise in intracellular
      calcium concentration, which is dependent on calcium influx through voltage
      sensitive calcium channels. Recent studies have indicated that the myogenic
      response in renal arteries is associated with the activation of phospholipase C
      and that arachidonic acid potentiates, whereas inhibitors of cytochrome P-450 and
      protein kinase C attenuate, this response. Renal arteries produce 20
      hydroxyeicosatetraenoic acid (20-HETE) via the cytochrome P-450 pathway when
      incubated with arachidonic acid. 20-HETE is a potent constrictor of canine and
      rat renal arterioles. It inhibits K+ channel activity, depolarizes renal vascular
      smooth muscle cells, and produces a sustained increase in intracellular calcium
      concentration. In this regard, the vasoconstrictor response to 20-HETE mimics the
      myogenic activation of renal arteries after elevations in transmural pressure.
      These studies suggest that the activation of phospholipase C and subsequent
      increases in the intracellular levels of diacylglycerol, 1,4,5 inositol
      triphosphate, and cytochrome P-450 metabolites of arachidonic acid may
      participate in the myogenic response of renal arteries and in the regulation of
      renal vascular tone.

PMID- 7506945
TI  - The effects of polar solutes on the viscoelastic behavior of elastin.
AB  - The viscoelastic behavior of arterial elastin in aqueous solutions of polar
      solutes has been studied to establish both its range of behavior and the
      mechanisms by which the behavior is altered by the solutes. We were particularly
      interested in whether a solute interacted directly with the elastin or whether it
      acted only indirectly to reduce the activity of water. The behavior of elastin in
      solutions of glucose, NaCl, ammonium sulphate, and in low concentrations of
      ethylene glycol was similar to that of elastin that had been directly dehydrated
      or indirectly dehydrated using osmotic agents such as dextran or polyethylene
      glycol. This similarity suggests that these solutes interact with elastin only
      indirectly. Thiocyanate and high concentrations of dimethyl sulfoxide and
      ethylene glycol appeared to interact directly with the elastin, altering both the
      swelling and the viscoelastic behavior of the network.

PMID- 7506946
TI  - Reductions in physiologic shear rates lead to CD11/CD18-dependent, selectin
      independent leukocyte rolling in vivo.
AB  - In this study, we tested the hypothesis that reducing shear rates in
      postcapillary venules causes CD18-dependent, selectin-independent leukocyte
      rolling. Intravital microscopy was used to assess shear rate-dependent leukocyte
      rolling in 25- to 40-microns rat mesenteric venules. Pretreatment of animals with
      25 mg/kg fucoidin, a carbohydrate moiety that binds to and inhibits selectin
      function, essentially abolished the number of spontaneously rolling leukocytes.
      When shear rates were reduced by 50% (from 438 +/- 36 s-1 to 222 +/- 19 s-1) in
      the presence of fucoidin, leukocyte rolling increased fourfold, suggesting a
      selectin-independent mechanism of leukocyte rolling. Administration of CL26, an
      anti-CD18 antibody, prevented the leukocyte rolling associated with reduced shear
      rates. A second objective was to determine if the integrin-mediated leukocyte
      rolling at reduced shear rates would lead to firm adhesion of leukocytes in the
      presence of a chemotactic stimulus. Animals were pretreated with fucoidin and 100
      nmol/L platelet-activating factor (PAF) was superfused over the mesentery.
      Fucoidin prevented leukocyte rolling and subsequent PAF-induced adhesion at
      normal shear rates; however, when shear rates were reduced by 50%, a significant
      CD18-dependent increase in leukocyte rolling (10-fold) and adhesion (5-fold) was
      noted within 15 minutes. These data raise the possibility that, at lower shear
      rates, as is the case in various inflammatory conditions, selectin-independent,
      CD18-dependent leukocyte rolling and subsequent adhesion can occur in
      postcapillary venules.

PMID- 7506947
TI  - Native associations of early hematopoietic stem cells and stromal cells isolated
      in bone marrow cell aggregates.
AB  - In suspensions of murine bone marrow, many stromal cells are tightly entwined
      with hematopoietic cells. These cellular aggregations appear to exist normally
      within the marrow. Previous studies showed that lymphocytes and stem cells
      adhered to stromal cells via vascular cell adhesion molecule 1 (VCAM1). Injection
      of anti-VCAM1 antibody into mice disrupts the aggregates, showing the importance
      of VCAM1 in the adhesion between stromal cells and hematopoietic cells in vivo.
      Early hematopoietic stem cells were shown to be enriched in aggregates by using a
      limiting-dilution culture assay. Myeloid progenitors responsive to WEHI-3CM in
      combination with stem cell factor (c-kit ligand) and B220- B-cell progenitors
      responsive to insulin-like growth factor-1 in combination with interleukin-7 are
      not enriched. We propose a scheme of stromal cell-hematopoietic cell interactions
      based on the cell types selectively retained within the aggregates. The existence
      of these aggregates as native elements of bone marrow organization presents a
      novel means to study in vivo stem cell-stromal cell interaction.

PMID- 7506948
TI  - Platelet glycoprotein IV (CD36) deficiency is associated with the absence (type
      I) or the presence (type II) of glycoprotein IV on monocytes.
AB  - Platelet membrane glycoprotein (GP) IV (also called CD36 and GPIIb) deficiency is
      associated with N(aka)-negative platelets. Using flow-cytometric analysis of
      cells stained with the monoclonal anti-GPIV antibody OKM5, we have studied the
      expression of GPIV on the monocytes from 16 healthy Japanese individuals whose
      platelets were deficient in GPIV. GPIV was absent on the surface of monocytes
      from 2 platelet GPIV-negative donors (type I), whereas it was present on the
      monocytes from the remaining 14 platelet GPIV-negative donors (type II). The
      fluorescent intensity of OKM5-stained type II monocytes was significantly (P <
      .05) lower than that of normal monocytes derived from platelet GPIV-positive
      donors, suggesting that the expression of GPIV on the type II monocytes is also
      abnormally regulated as compared with that on normal monocytes. OKM5 induced an
      oxidative burst in the type II monocytes as well as in the normal monocytes, but
      it failed to induce it in the type I monocytes. Because the 2 individuals with
      the type I deficiency have been healthy and exhibited no immunologic problems,
      GPIV appears to be not essential for the normal physiologic functions of
      monocytes. An anti-GPIV antibody was detected in the serum from one of the type I
      GPIV-deficient women, who had never received any blood transfusions but had given
      birth to three apparently healthy children. These results suggest that type I
      GPIV-deficient individuals may be at risk of developing an anti-GPIV isoantibody
      upon blood transfusion or pregnancy.

PMID- 7506949
TI  - Alteration of platelet function in dogs mediated by interleukin-6.
AB  - To determine if interleukin-6 (IL-6) administration influences platelet function,
      platelet activation was analyzed sequentially in IL-6-treated (80
      micrograms/kg/d) and control dogs. Platelet activation was determined in whole
      blood by flow cytometry by quantitating the binding of a monoclonal antibody to
      platelet surface P-selectin after stimulation with graded doses of thrombin.
      Administration of IL-6 resulted in a twofold decrease in the thrombin
      concentration required for induction of half-maximal P-selectin expression (ED50)
      compared with control animals. The ED50 returned to normal after cessation of IL
      6 administration. As measured by P-selectin expression, enhanced responsiveness
      to the strong agonist platelet activating factor (PAF) was also observed in the
      IL-6-treated dogs. IL-6 had no effect on the susceptibility of platelets to
      thrombin activation when incubated with anticoagulated dog blood. The data show
      that, in addition to augmenting the platelet count in normal dogs, IL-6 enhances
      the sensitivity of platelets to activation in response to thrombin and PAF.

PMID- 7506951
TI  - Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to
      CD20.
AB  - Murine monoclonal antibody 2B8 specifically recognizes the CD20 phosphoprotein
      expressed on the surface of normal B lymphocytes and B-cell lymphomas. The light-
      and heavy-chain variable regions of 2B8 were cloned, after amplification by the
      polymerase chain reaction, into a cDNA expression vector that contained human
      IgG1 heavy chain and human kappa-light chain constant regions. High-level
      expression of chimeric-2B8 antibody (C2B8) was obtained in Chinese hamster ovary
      cells. Purified C2B8 exhibited antigen binding affinity and human-tissue
      reactivity similar to the native murine antibody. In vitro studies showed the
      ability of C2B8 to bind human C1q, mediate complement-dependent cell lysis of
      human B-lymphoid cell lines, and lyse human target cells through antibody
      dependent cellular cytotoxicity. Infusion of macaque cynomolgus monkeys with
      doses ranging from 1.6 mg/kg to 6.4 mg/kg resulted in greater than 98% depletion
      of peripheral blood (PB) B cells and 40% to 70% depletion of lymph node B cells.
      Recovery of PB B cells usually started at 2 weeks after treatment and required 60
      to greater than 90 days to reach normal levels. As much as 95% depletion of B
      cells in peripheral lymph nodes and bone marrow was observed following weekly
      injections of 16.8 mg/kg antibody. No toxicity was observed in any of the
      animals. These results offer the possibility of using an "immunologically active"
      chimeric anti-CD20 antibody as an alternative approach in the treatment of B-cell
      lymphoma.

PMID- 7506950
TI  - Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and
      peripheral blood.
AB  - The cell-surface expression of the MIC2 antigen defined by the monoclonal
      antibody 12E7 was investigated on human leukocytes in bone marrow (BM), thymus,
      and peripheral blood (PB) using multiparameter flow cytometry and cell sorting.
      In contrast to preceding reports, we found that the MIC2 antigen is not
      restricted to T cells and monocytes. We show that it is also expressed in the B
      cell and in the granulocytic lineage, the levels of expression being related to
      distinct maturational stages. CD34+ cells of BM were found to express the antigen
      at high levels. Along the granulocytic maturation pathway from CD34+CD33+ blasts
      to mature granulocytes, MIC2 densities appeared progressively reduced with a
      considerable decline at the myelocyte stage. In B lymphopoiesis, the earliest
      CD34+ CD10+ B-cell precursor (BCP) cells, further subdivided by expression of
      CD19, displayed the highest MIC2 density of BM leukocytes. All later BCP stages
      showed lower MIC2 expression levels, with a remarkable reduction concomitant with
      loss of the CD34 antigen at the CD10+CD20- surface mu-chain- stage, and a
      subsequent slight upregulation along with maturation to CD10-CD20high surface mu
      chain+ BCPs. The brightest MIC2 expression of all cells tested was displayed by
      the most immature thymic T-lineage cells characterized by the antigenic profile
      CD34weakor- CD7++ surface CD3-CD1a(weak) CD4weak CD8-or weak. Common thymocytes
      stained slightly less intense with 12E7, whereas all subsequent stages of T
      lineage cells in thymus, PB, or BM showed markedly reduced MIC2 levels. Mature
      peripheral CD4+ as well as CD8+ T cells displayed a bimodal distribution of MIC2.
      In the CD4+ population, the distinct MIC2 levels were related to the well-studied
      functional subdivision by differential expression of CD45 isoforms, the helper
      inducer/memory subset showing higher MIC2 expression than helper-suppressor/naive
      CD4+ T cells. Similarly high MIC2 densities were found on CD16+ natural killer
      cells and on CD14+ monocytes, whereas mature peripheral B cells exhibited low or
      intermediate expression, and granulocytes exhibited no or only dim expression.
      These results document that the MIC2 antigen (1) is expressed on all leukocyte
      lineages; (2) is differentially expressed during T- and B-lymphoid, as well as
      granulocytic maturation; (3) shows highest expression in the most immature
      lymphocytic and granulocytic developmental stages; and (4) is also differentially
      expressed on functional T-cell subsets. We speculate that these observations
      imply a functional significance of MIC2 in the network of hematopoietic adhesion
      pathways.

PMID- 7506953
TI  - Cyclosporin A and cyclosporin SDZ PSC 833 enhance anti-CD5 ricin A-chain
      immunotoxins in human leukemic T cells.
AB  - Recent studies have shown that cyclosporin A (CsA) may affect ricin A-chain
      immunotoxin (RTA-IT) therapy. In this study, we evaluated the ability of CsA and
      its nonimmunosuppressive analog, SDZ PSC 833, to enhance anti-CD5 T101 RTA-ITs in
      vitro. Both 4 mumol/L CsA and 4 mumol/L SDZ PSC 833 significantly and
      specifically enhanced the cytotoxic activity of T101 RTA-IT on the human
      lymphoblastic T-cell line, CEM III (101-fold and 105-fold, respectively).
      Furthermore, these Cs also enhanced the cytotoxicity of the more potent T101
      F(ab')2 RTA-IT (ninefold and eightfold, respectively). The effect of human
      plasma, originating from four patients enrolled in a phase I high-dose CsA
      regimen, was examined on T101 RTA-IT cytotoxicity on CEM III cells. In each case,
      with plasma CsA levels between 3,090 and 4,860 ng/mL (2.5 to 4 mumol/L), a
      significant increase in T101 RTA-IT-mediated cytotoxicity was observed ranging
      from 31% to 60%. Neither CsA nor SDZ PSC 833 affected the rate of RTA-IT binding,
      internalization, intracellular trafficking, or degradation. Analysis of
      internalized T101 RTA-IT molecules showed that these were essentially intact,
      which suggests that these enhancers may act only on a small population of RTA-ITs
      that escapes present investigational techniques. In conclusion, because the
      concentrations used are clinically achievable, Cs appear to be promising agents
      for in vivo enhancement of RTA-ITs.

PMID- 7506952
TI  - Expression of the Kit and KitA receptor isoforms in human acute myelogenous
      leukemia.
AB  - Genetic and biologic evidence suggests that the Kit receptor tyrosine kinase is
      important in early events in hematopoietic stem cell differentiation. Two
      naturally occurring isoforms of the Kit receptor, termed Kit and KitA, were
      originally described in mouse cells and, subsequently, in human cells. These
      isoforms differ by the presence (KitA) or absence (Kit) of four amino acids (Gly
      Asn-Asn-Lys) that lie immediately outside the transmembrane domain. RNase
      protection was used to measure the levels of Kit and KitA mRNA in normal bone
      marrow and the blast cells from individuals with acute myelogenous leukemia
      (AML). Although both isoforms were present in all the AML samples tested, there
      was considerable heterogeneity in the relative levels of the two transcripts,
      with Kit to KitA RNA ratios varying from as low as 1.3 to as high as 12. In
      contrast, the ratio of Kit to KitA transcripts in normal bone marrow was tightly
      clustered between 4.4 and 5.5. Because alterations in the relative levels of
      expression of Kit and KitA may affect the ability of a cell to respond to the Kit
      ligand, Steel factor, we examined the Kit/KitA RNA ratio in AML patients that
      differed with respect to a number of diagnostic, prognostic, and biologic
      parameters. The relative levels of Kit to KitA RNA was independent of French
      American-British subtype, response to therapy, and primary and secondary plating
      efficiencies in vitro. Thus, these data suggest that the relative levels of the
      two isoforms of the Kit receptor in AML are not associated with any obvious
      biologic or clinical parameters and, therefore, may reflect naturally occurring
      changes in splicing mechanisms as stem cells differentiate.

PMID- 7506954
TI  - Activation of beta 1 integrin fibronectin receptors on HL60 cells after
      granulocytic differentiation.
AB  - Phorbol esters upregulate the functional affinity of beta 1 integrin receptors
      for fibronectin on human neutrophils and other leukocytes. We investigated the
      ability of phorbol myristate acetate (PMA) to stimulate the human promyelocytic
      cell line HL-60 to adhere to fibronectin, either in its undifferentiated state
      (HL60) or after dimethylsulfoxide-induced differentiation along the granulocytic
      pathway (dHL60). PMA stimulated little adherence of undifferentiated HL60 to
      fibronectin or to the 120-kD chymotryptic cell-binding domain (CBD) of
      fibronectin. In contrast, PMA stimulated dHL60 cells to rapidly adhere to both
      fibronectin- and to CBD-coated plastic. PMA-stimulated dHL60 adherence to
      fibronectin was largely mediated by both alpha 4 beta 1 and alpha 5 beta 1,
      whereas PMA-stimulated dHL60 adherence to CBD was largely mediated by alpha 5
      beta 1. There was little contribution from beta 2 integrins to PMA-stimulated
      dHL60 adherence to fibronectin or CBD. The inability of undifferentiated HL60 to
      adhere to fibronectin and CBD did not result from lack of expression of alpha 4
      beta 1 or alpha 5 beta 1 because HL60 and dHL60 express similar amounts of both
      alpha 4 beta 1 and alpha 5 beta 1 on their surface. In addition, 1 mmol/L Mn2+
      induced similar amounts of alpha 5 beta 1-dependent adherence of both HL60 and
      dHL60, showing that alpha 5 beta 1 on undifferentiated HL60 is capable of binding
      to its ligand. These data suggest that activation of protein kinase C cannot
      functionally upregulate these beta 1 integrins on undifferentiated HL60 cells.
      The development of PMA-stimulated beta 1-dependent adherence after granulocytic
      differentiation of HL60 cells suggests that the differentiated HL60 cell is a
      useful model for investigating functional coupling of protein kinase C to beta 1
      integrin in myeloid cells.

PMID- 7506955
TI  - Serum erythropoietin and erythropoiesis in high- and low-fetal hemoglobin beta
      thalassemia intermedia patients.
AB  - Clinical data suggest that in beta-thalassemia-intermedia patients, higher levels
      of circulating fetal hemoglobin (HbF) are associated with greater disease
      severity at comparable degrees of anemia. We assessed the influence of the amount
      of circulating HbF on serum erythropoietin (s-Epo) levels and on serum
      transferrin receptor, a measure of erythropoiesis, in 30 beta-thalassemia
      intermedia patients. Twenty-four showed more than 40% HbF (21 of whom with beta
      (0)-thalassemia) and 6 presented lower HbF levels (beta(+)-thalassemia). The two
      groups of patients did not differ in age (15.3 v 19 years, respectively) or
      degree of anemia (Hb = 8.8 g/dL in both groups). Log (s-Epo) was correlated
      inversely with Hb (r = -0.47; P < .01), and directly with HbF (r = .55; P <
      .001). Multivariate regression analysis showed that Hb and HbF were independently
      correlated with s-Epo levels. High-HbF patients had greater s-Epo values at the
      same Hb level than low-HbF patients. Considering that iron-deficiency anemia
      control patients represented the predicted physiologic response of s-Epo to
      anemia, the observed/predicted s-Epo ratio in low-HbF thalassemic patients was no
      different from controls, but was increased in the high-HbF group. High-HbF
      patients also showed an expansion of erythropoiesis as much as four to nine times
      the normal value at the same Hb level as low-HbF patients. We conclude that HbF
      exerts an independent regulatory effect on erythropoietin production and
      erythropoiesis that is detectable only when HbF levels exceed 40%.

PMID- 7506956
TI  - Oligoclonal expansion of CD8+ CD57+ T cells with restricted T-cell receptor beta
      chain variability after bone marrow transplantation.
AB  - A major expansion of CD8+57+ lymphocytes expressing an alpha-beta T-cell receptor
      (TCR) is frequent after bone marrow transplantation (BMT). We examined the
      clonality of the TCR beta gene repertoire in these expanded CD8+57+ cells after
      allogeneic or autologous BMT. We performed a polymerase chain reaction (PCR)
      analysis of the V beta chain usage in CD8+57+ cells purified from nine BMT
      recipients with a series of oligonucleotides specific for 20 V beta gene
      families. PCR products from selected TCR beta gene rearrangements were sequenced.
      The CD8+57+ cells from eight of nine patients used a restricted set of V beta
      families, with a marked predominance of two to three V beta gene families per
      patient, whereas the control autologous CD57- subset expressed the whole 20 V
      beta families. A direct sequencing analysis confirmed the V beta 16 and V beta 17
      clonality in six patients, showing a striking homology in the CDR3 sequences of
      the V beta 16 products. The CD8+57+ cells, but not the CD57- cells, displayed an
      oligoclonal pattern of TCR rearrangements as shown by PCR analysis of TCR gamma
      gene rearrangements. Such an oligoclonal expansion of CD8+57+ cells, using a
      restricted set of the V beta gene families, may result from a specific TCR
      stimulation of a limited number of T-cell clones in BMT recipients.

PMID- 7506957
TI  - Unusual type of ischemically induced synaptic degeneration studied by Hicks
      method.
AB  - This study describes the degenerating axonal termination and filamentous synaptic
      degeneration after 30 minutes spinal cord ischemia followed by 3 days survival
      using Hicks neurofibrillar impregnation. From laminoarchitectonic point of view a
      clear evidence was gained supporting the original description obtained by Nauta
      method. The majority of degenerated boutons revealed by Hicks method was found in
      the deep layers of the dorsal horn and then with increasing density in the
      intermediate zone and partly in the neuropil of the anterior horn. These results
      confirm the ability of Hicks method as a reliable tool in systematic research of
      the ischemically damaged synaptic contacts.

PMID- 7506958
TI  - Antisense sequences of 20-kDa homologous restriction factor (HRF20) are found in
      C9 and the C8 beta chain of homologous complement.
AB  - We examined, on the basis of the fact that sense and antisense peptides have
      affinity for each other, whether any relationship exists between homologous
      restriction factor (HRF20), a membrane inhibitor of the terminal stage of
      homologous complement attack, and the antisense sequence of the terminal
      complement components C8 and C9. In this article, we demonstrate that there are
      two regions of C9 that contain antisense sequences to one continuous region of
      HRF20 and that this relationship exists between human HRF20 and human C9, but not
      mouse C9. We also found one region of the C8 beta chain that contains an
      antisense sequence to HRF20.

PMID- 7506959
TI  - Expression and functional characterization of recombinant human vascular cell
      adhesion molecule-1 (VCAM1) synthesized by baculovirus-infected insect cells.
AB  - Vascular cell adhesion molecule-1 (VCAM1) is a cell surface glycoprotein produced
      by the vascular endothelium, as well as on macrophage-like and dendritic cell
      types, in response to certain inflammatory stimuli. VCAM1 interacts with the
      integrin VLA4 present on mononuclear leukocytes. We have isolated the cDNA for
      VCAM1 using RT-PCR by screening a cDNA library from IL-1 beta-activated human
      endothelial cells. To obtain large quantities of VCAM1 for structural and
      functional studies, we have produced this protein in insect cells using a
      baculovirus expression system. Insect cells infected with recombinant virus
      synthesized human VCAM1 at levels exceeding 3% of total cellular protein
      following 72 h postinfection. VCAM1-expressing insect cells were shown to bind
      specifically to a variety of VLA4 expressing cell lines (Jurkat, THP-1, U937).
      Thus, recombinant VCAM1 protein produced in the baculovirus expression system was
      localized to the cell surface and was biologically active. Large-scale
      availability of this adhesion protein should enhance efforts toward the discovery
      of new antiadhesive (anti-inflammatory and antiatherogenic) therapeutics.

PMID- 7506960
TI  - Stereo-electron microscopy of DNA-stained mitotic chromosomes from Dictyostelium
      discoideum.

PMID- 7506961
TI  - Comparative expression of endogenous retrotransposons in adult mouse mammary
      gland during normal development and differentiation.
AB  - Amplified expression of the endogenous retrotransposons, intracisternal A
      particles (IAPs) and murine leukemia virus-related elements (MLVEs), along with
      decreased expression of VL30 elements frequently occurs during mouse mammary
      tumorigenesis. We have now analyzed the expression of these retroelements during
      the normal developmental and differentiation cycle of the mammary gland as found
      in virgin, pregnant, lactating, and postlactation adult female BALB/c mice.
      Retrotransposon expression was either unchanged or decreased during the
      progressive stages of the cycle compared to virgin tissue. Likewise, growth of
      mammary epithelial cells in primary culture had little or no effect on expression
      of IAPs, MLVEs and VL30 sequences. Thus, the dramatic changes involving these
      retrotransposons in many mouse mammary tumors appear unrelated to any normal
      state.

PMID- 7506962
TI  - Detection of behavioral, developmental, and psychosocial problems in pediatric
      primary care practice.
AB  - By virtue of their ongoing relationship with families and young children,
      pediatric primary care providers are well positioned to participate in the early
      detection of children's behavioral, developmental, and psychosocial problems. Yet
      research suggests that many such problems elude early detection. Awareness of the
      prevalence of such problems should encourage pediatric providers to carefully
      elicit parents' opinions and concerns, obtain a relevant behavioral and
      developmental history, skillfully observe parent and child behaviors, and obtain,
      when indicated, the opinions of such other relevant professionals as preschool
      teachers. Possible strategies to improve early detection include the use of
      parent questionnaires, parent record-keeping of children's behavior, and a
      developmental screening tool as an aid to surveillance. The development of a
      classification system for such problems designed for primary care, rather than
      psychiatry, should also facilitate early detection.

PMID- 7506963
TI  - Electrophysiologic characteristics of glial cells.

PMID- 7506964
TI  - Changes in cytokeratin, vimentin and desmoplakin distribution during the repair
      of irradiation-induced lung injury in adult rats.
AB  - The expression of cytokeratins, desmoplakin and vimentin has been studied
      immunohistochemically in the rat lung injured by x-irradiation using 14 well
      characterized monoclonal antibodies. A time-dependent relationship between the
      cytokeratin expression pattern and the morphological alterations observed was
      apparent. A cytokeratin 8 and 18 expression in normally cytokeratectable even at
      3-6 h after irradiation. Between 14 days and 2 months, a remarkable heterogeneity
      in the epithelial cell cytokeratin pattern and an increasing immunoreaction for
      desmoplakin was found. In terminal bronchial epithelial cells, a heterogeneous
      CK8, 18 and 19 staining and a neoexpression of cytokeratins 4 and 7 was detected.
      Finally, peribronchiolar and vascular smooth muscle cells were cytokeratin
      positive. At 6 months after irradiation, cytokeratin 13 and vimentin were focally
      present in bronchial epithelial cells and atypical type I and II pneumocytes as
      well as scattered epithelioid cell complexes were noted. During the course of
      injury, a loss of type III alveolar epithelial cells was found, which was
      characterized in the rat by a specific globular cytokeratin pattern and
      restricted immunoreactivity with cytokeratin-specific antibodies. These results
      show that the expression pattern of cytokeratins is a sensitive marker in
      monitoring epithelial alterations during lung injury.

PMID- 7506965
TI  - Marden-Walker syndrome: a case report and a critical review of the literature.
AB  - We present a patient with blepharophimosis, joint contractures, immobile facies,
      decreased muscular bulk, postnatal growth retardation, developmental delay,
      micrognathia, cleft palate, camptodactyly, arachnodactyly, pectus,
      kyphoscoliosis, hypospadias, and absent deep tendon reflexes. These findings are
      consistent with Marden-Walker syndrome (MWS). Twenty-two additional cases in the
      literature are reviewed. Diagnostic criteria are proposed, and the spectrum of
      variability is discussed. Evidence for autosomal recessive inheritance is
      reviewed as is the differential diagnosis. Possible pathogenetic mechanisms are
      considered.

PMID- 7506966
TI  - An apparently new syndrome of bowed tibiae, radial anomalies, osteopenia,
      multiple fractures and developmental delay.
AB  - We report two siblings with bowed tibia, hypoplastic thumbs, multiple fractures,
      a distinctive facial phenotype and developmental delay. These children share some
      features with other cases reported in the literature but we consider that they
      represent a new syndrome.

PMID- 7506968
TI  - A new syndrome of multiple joint dislocations with metaphyseal dysplasia.
AB  - A 15-day-old female child is presented with multiple joint dislocations who died
      during the neonatal period. She had additional features of metaphyseal dysplasia,
      deficient calcification of vault of the skull, growth retardation, a natal tooth,
      lymphoedema and facial dysmorphism. This may constitute a new syndrome of
      multiple joint dislocations with metaphyseal dysplasia.

PMID- 7506967
TI  - Toriello-Carey syndrome: report of a new case.
AB  - Toriello-Carey syndrome is a malformation syndrome characterized by cranio-facial
      defects, visceral defects, congenital heart defects, hypotonia, and postnatal
      growth retardation. To our knowledge, only five patients with this condition have
      been reported. We describe another case of the Toriello-Carey syndrome extending
      the phenotypic manifestations of the syndrome.

PMID- 7506969
TI  - Transient association of the HNK-1 epitope with 5'-nucleotidase during
      development of the cat visual cortex.
AB  - During early postnatal development of the kitten visual cortex the ectoenzyme 5'
      nucleotidase undergoes a characteristic redistribution. Until about postnatal
      week 6 it is essentially confined to synaptic contacts in input layer IV and its
      expression is related to the use-dependent segregation of thalamic afferents into
      ocular dominance columns. Subsequently, 5'-nucleotidase becomes distributed
      uniformly throughout all layers and is then associated selectively with glial
      cells. Here we describe an age-dependent alteration in the expression of a
      carbohydrate epitope of 5'-nucleotidase which correlates with the developmental
      change of the enzyme's localization. We have isolated 5'-nucleotidase from the
      occipital cortex of kittens of varying age and from adult cats and investigated
      by immunoblotting the association of the HNK-1 carbohydrate epitope with the
      protein. 5'-Nucleotidase carries the HNK-1 epitope in kittens of 3-9 weeks but
      the epitope is absent from 12-week-old kittens or adult cats. Thus, the
      appearance of the HNK-1 epitope correlates with the transient localization of the
      enzyme at synapses. The HNK-1 carrying 5'-nucleotidase may be involved in
      synaptogenesis and use-dependent modifications of synaptic connections.

PMID- 7506970
TI  - Endogenous histamine in cultured bovine adrenal chromaffin cells.
AB  - Histamine releases catecholamines and opioids in primary cultured bovine adrenal
      medullary (BAM) chromaffin cells. We have studied whether histamine is
      synthesized and localized in BAM cells, and whether it can be released upon
      activation with secretagogues. In BAM cells histamine is immunohistochemically co
      localized with tyrosine hydroxylase in 45 +/- 8% of all cells. Only histamine
      immunoreactivity was observed in 8 +/- 2% of all BAM cells. No mast-cell-like
      cells were observed in our system. Histamine can be released from BAM cells by
      high potassium (56 mM K+) in a calcium-dependent manner. Compound 48/80 did not
      release histamine from BAM cells but nicotine caused a dose-dependent liberation
      of the amine. Cultured BAM cells have histidine decarboxylase activity which is
      inhibited by alpha-fluoromethylhistidine. These results indicate that endogenous
      histamine is synthesized, stored and released in BAM chromaffin cells in vitro.

PMID- 7506971
TI  - Organization of auditory callosal connections in hypothyroid adult rats.
AB  - Callosal connections were studied with tracers (horseradish peroxidase (HRP) and
      wheat germ agglutinin-horseradish peroxidase (WGA-HRP)) in normal rats and rats
      deprived of thyroid hormones with methimazole (Sigma) since embryonic day 14 and
      thyroidectomized at postnatal day 6. In hypothyroid rats, the auditory areas, in
      particular the primary auditory area, showed cytoarchitectonic changes including
      blurred lamination and decrease in the size of layer V pyramidal neurons. In
      control rats, callosally-projecting neurons were found between layers II and VI
      with a peak in layer III and upper layer IV. In hypothyroid rats, labelled
      neurons were found between layers IV and VI with two peaks corresponding to layer
      IV and upper layer V, and in upper layer VI. Quantitative analysis of radial
      distribution of callosally-projecting neurons confirmed their shift to
      infragranular layers in hypothyroid rats. Three-dimensional reconstructions
      showed a more continuous tangential distribution of callosally-projecting neurons
      in hypothyroid rats which may be due to the maintenance of a juvenile 'exuberant'
      pattern of projections. These changes in cortical connectivity may be relevant
      for understanding epilepsy and mental retardation associated with early
      hypothyroidism in humans and to clarify basic mechanisms of cortical development.

PMID- 7506972
TI  - Stochastic geometry and electronic architecture of dendritic arborization of
      brain stem motoneuron.
AB  - We describe how the stochastic geometry of dendritic arborization of a single
      identified motoneuron of the rat affects the local details of its electrotonic
      structure. After describing the 3D dendritic geometry at high spatial resolution,
      we simulate the distribution of voltage gradients along dendritic branches under
      steady-state and transient conditions. We show that local variations in diameters
      along branches and asymmetric branchings determine the non-monotonous features of
      the heterogeneous electrotonic structure. This is defined by the voltage decay
      expressed as a function of the somatofugal paths in physical distances (voltage
      gradient). The fan-shaped electrotonic structure demonstrates differences between
      branches which are preserved when simulations are computed from different values
      of specific membrane resistivity although the absolute value of their voltages is
      changed. At given distances from soma and over long paths, some branches display
      similar voltages resulting in their grouping which is also preserved when
      specific membrane resistivity is changed. However, the mutual relation between
      branches inside the group is respecified when different values of specific
      membrane resistivity are used in the simulations. We find that there are some
      invariant features of the electrotonic structure which are related to the
      geometry and not to the electrical parameters, while other features are changed
      by altering the electrical parameters. Under transient conditions, the
      somatofugal invasion of the dendritic tree by a somatic action potential shifts
      membrane potentials (above 10 mV) of dendritic paths for unequal distances from
      the soma during several milliseconds. Electrotonic reconfigurations and membrane
      shifts might be a mechanism for postsynaptic plasticity.

PMID- 7506973
TI  - Temporal integration in visual cortex of cats with surgically induced strabismus.
AB  - Single unit response latencies in striate cortex after visual stimulation with
      stationary flashed bars were measured and interocularly compared in anaesthetized
      cats with surgically induced strabismus, in order to elucidate the neural basis
      of strabismic amblyopia. Four unilateral esotropic and two exotropic cats were
      studied. The visual onset latencies of cortical neurons ranged from 30 to 170 ms
      after stimulation of the non-deviating eye at a contrast of 82%. Responses after
      visual stimulation of the deviating eye were consistently delayed by
      approximately 10 ms. The latency increase was independent of the direction and
      absolute angle of squint in the different animals. Peak latencies of cortical
      neurons ranged from 43 to 245 ms. Median peak latency was 85 ms for the non
      deviating and 95 ms for the deviating eye. The rise time of cortical flash
      responses, as determined from onset-peak differences, ranged between 2 and 170
      ms. Direct interocular comparison of response latencies in the remaining
      binocular neurons revealed an invariable advantage for the non-deviating eye.
      Supragranular neurons showed a greater interocular latency difference than
      neurons in layer IV. Visual latencies were contrast-dependent. However, the
      latency reduction with increasing contrast was less pronounced for the deviating
      eye. We discuss the possibility that central integration times, especially within
      cortex, are prolonged in strabismic cats, affecting temporal coincidence of
      signal processing in the visual cortex. The resulting disturbance of spatio
      temporal integration, as caused by a scrambling of geniculo-striate and
      intracortical connections, may be the substrate of binocular suppression and
      strabismic amblyopia.

PMID- 7506974
TI  - Large calibre primary afferent neurons projecting to the gracile nucleus express
      neuropeptide Y after sciatic nerve lesions: an immunohistochemical and in situ
      hybridization study in rats.
AB  - Using immunohistochemistry and in situ hybridization, we studied changes in
      expression of some neuropeptides in large and medium-sized neurons in lumbar 4
      and 5 rat dorsal root ganglia projecting to the gracile nucleus, in response to
      peripheral axotomy. Fourteen days after unilateral sciatic nerve transection,
      many large neurons and some medium-sized neurons in ipsilateral dorsal root
      ganglia were strongly neuropeptide Y-positive. Galanin-, vasoactive intestinal
      polypeptide (VIP)- and peptide histidine-isoleucine (PHI)-like immunoreactivities
      coexisted with neuropeptide Y-like immunoreactivity in some of these neurons.
      After axotomy numerous large and medium-sized cells contained neuropeptide Y mRNA
      in the ipsilateral ganglia, whereas no hybridization was seen in the
      contralateral or control ganglia. Cross-sectioned, large neuropeptide Y-positive
      fibres were observed in a somatotopically appropriate zone within the ipsilateral
      gracile fasciculus. A dense network of neuropeptide Y-immunoreactive, large nerve
      fibres and terminals was seen in the ipsilateral gracile nucleus. A small number
      of galanin- and VIP/PHI-like immunoreactive nerve fibres and terminals were also
      observed in adjacent sections. Neuropeptide Y-like immunoreactivity colocalized
      with galanin- or VIP/PHI-like immunoreactivity in some nerve fibres. None of
      these neuropeptide immunoreactivities could be detected in nerve fibres and
      terminals in the control or contralateral gracile nucleus. These findings suggest
      that neuropeptides, in addition to their role in small dorsal root ganglion
      neurons, may have a function in large and medium-sized dorsal root ganglion
      neurons projecting to laminae III and IV in the dorsal horn as well as to the
      gracile nuclei, as a part of their response to peripheral axotomy.

PMID- 7506975
TI  - Galanin antagonists block galanin-induced feeding in the hypothalamus and
      amygdala of the rat.
AB  - Galanin significantly increased food intake when microinjected into the region of
      the central nucleus of the amygdala as well as into the paraventricular nucleus
      of the hypothalamus. In the amygdala this effect was specific to feeding; no
      change in grooming, resting, or other behaviour was observed after galanin
      treatment. These results provide evidence that the amygdala may be an important
      site in the mediation of galanin-induced feeding. The galanin receptor
      antagonists, C7 and M40, antagonized galanin-induced feeding, while having no
      effect alone on food consumption in free-feeding rats. These new galanin receptor
      antagonists provide useful tools for further investigating the role of endogenous
      galanin in the regulation of feeding.

PMID- 7506977
TI  - Essential drugs for palliative care.

PMID- 7506976
TI  - Evaluation of symptomatology in planning palliative care.
AB  - Cross-sectional surveys are a useful tool in planning health care, both in the
      community and in hospitals. We found that a review of routine case records did
      not yield sufficient information for planning palliative care services in the
      hospital environment, and therefore decided to conduct a cross-sectional survey
      involving random patients attending the outpatient division of the Regional
      Cancer Centre, Trivandrum, India. Three hundred and twelve patients were
      interviewed, and pain and weight loss were found to be the most prominent
      symptoms (> 90%). This study indicates that symptomatology has to be addressed in
      detail while planning palliative care services in a hospital setting. Even with
      its selection bias, the study provides valuable clues for the adequate
      organization and continuation of palliative care services.

PMID- 7506978
TI  - 'Good palliative care' orders.
AB  - A Select Committee of the Parliament of South Australia, considering revisions to
      legislation governing care of the dying, did not support allowing doctors to
      assist suicide. They recommended that no liability attach to the provision of
      reasonable palliative care which happens to shorten life. The Committee affirmed
      the suggestion that positive open orders to provide 'good palliative care' should
      replace 'do not resuscitate' orders.

PMID- 7506979
TI  - Palliative/hospice care in Poland.
AB  - The first hospice in eastern Europe was the Hospicium in Krakow, which was
      created 10 years ago. Three years later the leading independent Polish hospice,
      Hospitium Pallotinum, was founded in Gdansk. This hospice helped to organize more
      than 20 similar groups, usually Catholic agencies which offer home care
      programmes. The University Palliative Care Service in the Academy of Medical
      Sciences in Poznan, which was created in 1988, consists of a home care team
      caring for 600 patients a year and has a seven-bed inpatient unit. It offers an
      education programme for physicians, nurses, medical and pharmacy students as well
      as a research programme. There is currently an academic link between the Poznan
      Palliative Care service and Sir Michael Sobell House in Oxford, sharing medical
      and nursing education in palliative care. The educational courses and conferences
      have been attended by international speakers offering education which will help
      to change the attitudes of professional health care workers and the public. We
      hope that the Polish Ministry of Health and Welfare and the government will be
      interested in establishing policies that will cover the cost of palliative care
      in the newly developing health care system.

PMID- 7506980
TI  - Microwave-accelerated cytochemical stains for the image analysis and the electron
      microscopic examination of light microscopy diagnostic slides.
AB  - Recent studies in our laboratories have shown how microwave (MW) irradiation can
      accelerate a number of tissue-processing techniques, especially staining, to aid
      in the preparation of single specimens on glass microscope slides or coverslips
      for examination by light microscopy (and electron microscopy, if required) for
      diagnostic purposes. Techniques have been developed, which give permanently
      stained preparations, that can be studied initially by light microscopy, their
      areas of interest mapped, and computer-automated image analysis performed to
      obtain quantitative information. This is readily performed after MW-accelerated
      staining with silver methenamine by the Giammara-Hanker PATS or PATS-TS reaction.
      This variation of the PAS reaction gives excellent markers for specific
      infectious agents such as lipopolysaccharides for gram-negative bacteria or
      mannans for fungi. It is also an excellent stain for glycogen and basement
      membranes and an excellent marker for type III collagen or reticulin in the
      endoneurium or perineurium of peripheral nerve or in the capillary walls. Our
      improved MW-accelerated Feulgen reaction with silver methenamine for nuclear DNA
      is useful to show the nuclei of bacteria and fungi as well as of cells they are
      infecting. Improved coating and penetration of tissue surfaces by
      thiocarbohydrazide bridging of ruthenium red, applied under MW-acceleration,
      render biologic specimens sufficiently conductive for SEM so that sputter coating
      with gold is unnecessary. The specimens treated with these highly visible
      electron-opaque stains can be screened with the light microscope after mounting
      in polyethylene glycol (PEG) and the structures or areas selected for EM study
      are mapped with a Micro-Locator slide. After removal of the water soluble PEG the
      specimens are remounted in the usual EM media for scanning electron microscopy
      (SEM) or transmission electron microscopy (TEM) study of the mapped areas. By
      comparing duplicate smears from areas of infection, such as two coverslips of
      buffy coat smears of blood from a patient with septicemia, the microorganisms
      responsible can occasionally be classified for antimicrobial therapy long before
      culture results are available; gram-negative bacteria are positive with the
      Giammara-Hanker PATS-TS stain, and gram-positive bacteria are positive with the
      SIGMA HT40 Gram stain. The gram-positive as well as gram-negative bacteria are
      both initially stained by the crystal violet component of the Gram stain. The
      crystal violet stain is readily removed from the gram-negative (but not the gram
      positive) bacteria when the specimens are rinsed with alcohol/acetone. If this
      rinse step is omitted, the crystal violet remains attached to both gram-negative
      and gram-positive bacteria. It can then be rendered insoluble, electron-opaque,
      and conductive by treatment with silver methenamine solution under MW
      irradiation. This metallized crystal violet is a more effective silver stain than
      the PATS-TS stain for a number of gram-negative spirochetes such as Treponema
      pallidum, the microbe that causes syphilis.

PMID- 7506981
TI  - Reverse transcriptase PCR amplification of EWS/FLI-1 fusion transcripts as a
      diagnostic test for peripheral primitive neuroectodermal tumors of childhood.
AB  - The peripheral primitive neuroectodermal tumors (pPNETs) of childhood, including
      Ewing's sarcoma, peripheral neuroepithelioma, and Askin's tumor, often present
      significant diagnostic challenges for the anatomic pathologist. One consistent
      feature of these tumors is the presence of the t(11;22)(q24;q12) in tumor cells,
      and this translocation has been useful as a marker for this group of tumors. The
      recent cloning of the t(11;22) breakpoint has revealed the fusion of the human
      FLI-1 gene on chromosome 11q24 with a gene of unknown function called EWS on
      22q12, and fusion transcripts have been detected. These findings have raised the
      possibility of using molecular genetic analysis as a tool to diagnose pPNETs. To
      this end, we have tested pPNETs for the presence of EWS/FLI-1 fusion transcripts
      by reverse transcriptase-polymerase chain reaction (RT-PCR) using EWS and FLI-1
      specific primers. Eight (80%) of 10 pPNET cell lines were positive for amplified
      products using this technique. These results were confirmed by Southern analysis,
      which revealed rearrangements of EWS using genomic EWS probes in all eight
      positive cell lines. We then tested 20 primary pPNET tumors, and identified
      fusion transcripts by RT-PCR in 18 (90%) of these cases. Cloning and sequencing
      of PCR products confirmed the presence of EWS and FLI-1 sequences in these
      products. Furthermore, fusion transcripts were not detected by this technique in
      a series of non-pPNET pediatric solid tumors. Detection of EWS/FLI-1 fusion
      transcripts by RT-PCR therefore provides a novel adjunctive tool in the diagnosis
      of pPNETs.

PMID- 7506982
TI  - Detection of clonal immunoglobulin heavy chain gene rearrangements by polymerase
      chain reaction in scrapings from archival hematoxylin and eosin-stained
      histologic sections: implications for molecular genetic studies of focal
      pathologic lesions.
AB  - Using a simple scraping technique to obtain DNA directly from archival
      hematoxylin and eosin-stained slides, we successfully amplified clonal
      immunoglobulin heavy chain gene rearrangements (IGR) from lymphomatous
      infiltrates, as small as 1 mm2. The fragments amplified by the polymerase chain
      reaction (PCR) were identical in size to those from corresponding whole unstained
      sections freshly cut from the paraffin-embedded blocks. Using this technique, we
      detected clonal IGR from the scraping of a small lymphomatous nodule in the
      colon, although no amplified fragments were detected from the whole section.
      Furthermore, we demonstrated that two morphologically different areas in a case
      of B-cell lymphoma have identical amplified fragments. It is important that no
      amplified fragments were detected in scrapings from adjacent nonneoplastic areas.
      Although DNA recovered from scrapings was partially degraded, fragments as large
      as 725 base pairs were successfully amplified from a slide stored more than 11
      years. This technique thus allows detection of clonal IGR in tissues focally
      involved by B-cell lymphoma and molecular genetic studies of focal pathologic
      lesions as an alternative to in situ hybridization or in situ PCR. Finally, this
      technique can be applied to archival slides when tissue blocks are not available.

PMID- 7506983
TI  - Quantitative analysis of Her-2/neu (ERBB2) gene expression using reverse
      transcriptase polymerase chain reaction.
AB  - Inappropriate expression of Her-2/neu (ERBB2) gene has been associated with
      impaired breast cancer prognosis, suggesting a functional role in tumor
      progression. Herein we describe a quantitative method for analysis of Her-2/neu
      gene messenger RNA (mRNA), which employs reverse transcriptase polymerase chain
      reaction (RT-PCR) on a 10-microns cryostat section. The technique combines
      modified RNA extraction with complementary DNA (cDNA) synthesis to achieve a high
      level of sensitivity. Utilizing this PCR-based gene expression assay, we were
      able to quantitate variable amounts of Her-2/neu mRNA in cell lines with
      established levels of gene expression and in clinical human breast cancer
      specimens. In clinical samples, mRNA levels correlated with intensity of
      immunoperoxidase staining for corresponding oncoprotein. We conclude that PCR
      based mRNA quantitation can be applied to quantitative analysis of Her-2/neu gene
      expression, and potentially many other genes, in samples of limited size.

PMID- 7506984
TI  - Nitric oxide synthase-immunoreactive nerve fibers in dog cerebral and peripheral
      arteries.
AB  - Nitric oxide synthase (NOS)-immunoreactive fibers innervating the dog arterial
      wall were histochemically determined by the use of NOS antiserum. NOS
      immunoreactive fibers were consistently found in every arterial wall examined. In
      a whole-mount preparation, NOS-positive fibers were detectable in the small pial
      artery having a diameter of about 100 microns as well as the proximal middle
      cerebral artery. Further detailed analyses in thin cryostat sections indicated
      that in middle cerebral, basilar, temporal, mesenteric and femoral arteries, fine
      NOS-positive fibers were detected in outer zones of the media in addition to many
      thicker fibers in the adventitia. However, in the coronary artery, many thick
      fibers were situated in the adventitia, and fine NOS-positive fibers were not
      found in the media. Injection of ethanol to the pterygopalatine ganglion markedly
      decreased or abolished the NOS immunoreactivity in nerve cells and fibers and
      abolished the innervation of NOS-positive fibers in the wall of middle cerebral
      artery of the ipsilateral side. Together with findings in our previous
      publications concerning the functional role of nitroxidergic nerve in the control
      of arterial tone, we conclude that perivascular nerves containing NOS are crucial
      in eliciting the neurally induced, NO-mediated arterial relaxation.

PMID- 7506985
TI  - Pharmacological modification of glutamate neurotoxicity in vivo.
AB  - The ability of five agents (dizocilpine [MK-801], 2,3-dihydroxy-6-nitro-7
      sulfamoyl-benzo(F)-quinoxaline [NBQX], enadoline [CI-977], L-nitroarginine methyl
      ester [L-NAME] and BW 1003c87) with well defined, distinct pharmacological
      profiles and with established anti-ischemic efficacy, to modify neuronal damage
      has been examined in a simple in vivo model of glutamate excitotoxicity. Cortical
      lesions were produced in physiologically-monitored halothane-anesthetised rats by
      reverse dialysis of glutamate. The volume of the lesion was quantified
      histologically by image analysis of approximately 20 sections taken at 200 microm
      intervals throughout the lesion. The AMPA and NMDA receptor antagonists (NBQX and
      MK-801) and the inhibitor of nitric oxide synthase (L-NAME) significantly reduced
      the lesion volume by a similar extent (by approximately 30% from vehicle). Two
      agents (the kappa opioid agonist, CI-977 and the sodium channel blocker, BW
      1003c87) which putatively inhibit the release of endogenous glutamate
      presynaptically, had dissimilar effects on lesion size. CI-977 failed to alter
      the amount of damage produced by exogenous glutamate, whereas BW 1003c87 reduced
      the lesion size by approximately 50%. Using this model, the neuroprotective
      effects of anti-ischemic drugs can be explored in vivo, uncomplicated in contrast
      to experimental ischemia by reduced oxygen delivery, drug effects on tissue blood
      flow and compromised energy generation. In consequence, additional mechanistic
      insight into anti-ischemic drug action in vivo can be obtained.

PMID- 7506986
TI  - Modulation of acetylcholine release in rat hippocampus by amino alcohols and Bay
      K 8644.
AB  - The amino alcohols ethanolamine, R-alaninol and R-prolinol were shown to enhance
      high potassium evoked release of [3H]acetylcholine from hippocampal slices by
      monitoring fractional release of tritium during superfusion. This action appeared
      to be unique to hippocampal cholinergic nerve terminals because R-prolinol did
      not modulate evoked release of acetylcholine from cortical or striatal slices,
      dopamine from striatal slices or norepinephrine from hippocampal slices. Bay K
      8644, a dihydropyridine activator of calcium L-channels, exhibited a similar
      specificity profile. Bay K 8644 decreased the EC50 of R-prolinol without changing
      the maximal response, indicating that the actions of these two compounds converge
      through a common cellular mechanism. The effect of R-prolinol was blocked by the
      L-channel antagonists diltiazem and verapamil but not by nifedipine. In contrast,
      nifedipine only and not diltiazem or verapamil, blocked the enhancement induced
      by Bay K 8644. It appears then that amino alcohols can modulate the release of
      acetylcholine in the hippocampus possibly by enhancing calcium entry into nerve
      terminals through a specific activation of presynaptic L-channels at a site other
      than that which interacts with dihydropyridines.

PMID- 7506987
TI  - Exogenous prostacyclin, but not prostaglandin E2, produces similar responses in
      both G6PD activity and RNA production as mechanical loading, and increases IGF-II
      release, in adult cancellous bone in culture.
AB  - Cyclic mechanical loading in vivo that leads to new bone formation is also
      associated in osteocytes and surface bone cells with almost immediate increases
      in G6PD activity, and later increases in RNA production. Both these early,
      loading-related, responses can be reproduced in organ culture of adult cancellous
      bone, and both are abolished by the presence of indomethacin in the culture
      medium at the time of loading. The implication that prostaglandins (PGs) are
      involved in the control of loading-related osteogenesis is supported by increases
      in prostacyclin (PGI2) and PGE2 release from cores of cancellous bone during
      loading. In the experiments reported here, PGE2 and PGI2 were added exogenously
      (10(-6) M) to perfusable cores of adult canine cancellous bone to determine
      whether they would simulate the loading-related responses in G6PD activity and
      RNA synthesis. PGE2 increased G6PD activity in surface cells and osteocytes
      within 8 minutes but had no effect on [3H]-uridine incorporation at 6 hours. PGI2
      stimulated both G6PD activity and [3H]-uridine incorporation equally in
      osteocytes and surface cells. Neither PG produced any significant change in
      medium concentrations of IGF-I, and PGE2 had no effect on IGF-II. In contrast
      PGI2 elevated the medium concentration of IGF-II threefold. IGF-I and IGF-II were
      localized immunocytochemically to osteocytes and surface cells in both treated
      and untreated cores. Prostacyclin, but not PGE2, appears to imitate the early
      loading-related increases in G6PD activity and RNA synthesis in bone cells in
      situ. Prostacyclin, but not PGE2, also stimulates the early release of IGF-II.

PMID- 7506988
TI  - Alpha-fetoprotein glycosylation is abnormal in some hepatocellular carcinoma,
      including white patients with a normal alpha-fetoprotein concentration.
AB  - Lectin-affinity analyses with Lens culinaris agglutinin (LCA) and other lectins
      have demonstrated that the glycosylation of alpha-fetoprotein (AFP) secreted by
      hepatocellular carcinomas (HCC) is frequently altered when the serum AFP
      concentration is increased. To determine if AFP LCA-binding properties are
      altered in patients with HCC whose serum AFP concentration is normal, the
      percentage of LCA-binding AFP in serum from white newborns, white normal adults,
      white patients with chronic hepatitis and hereditary tyrosinemia and white and
      black patients with HCC were determined. The serum LCA-binding AFP fraction was
      low in newborns (1-4%) and normal adults (1-8%). There was a significant increase
      in LCA-binding AFP in patients with chronic hepatitis (10-24%) and hereditary
      tyrosinemia (5-35%). The AFP LCA-binding fraction was clearly abnormal (greater
      than 40%) in three of the white patients with an HCC and a normal serum AFP
      concentration, and the range of values (10-63%) in these HCC patients was similar
      to that seen in both white and black patients with HCC accompanied by increased
      AFP concentrations.

PMID- 7506990
TI  - Decreased expression of prostatic secretory protein PSP94 in prostate cancer.
AB  - cDNA libraries were generated from the prostate gland tissue obtained from a
      normal donor and from a patient with prostate cancer. Subtractive cDNA cloning
      was used to identify phenotype-specific cDNA sequences from both normal and
      cancerous prostate tissue. One clone, pN44, isolated from normal prostate tissue,
      codes for the prostate protein PSP94, expression of which appeared to be down
      regulated in the cancerous cells. Rabbit antisera against PSP94 were generated,
      and these antisera can be used to detect PSP94 in urine. Two other clones, pN23a
      and pN141f, were also found to be down-regulated.

PMID- 7506989
TI  - 2-Nitropropane-induced liver DNA and RNA base modifications: differences between
      Sprague-Dawley rats and New Zealand white rabbits.
AB  - 2-Nitropropane (2-NP), a hepatocarcinogen in male Sprague-Dawley rats but not,
      under the same conditions, in male New Zealand White rabbits, induces
      characteristic base modifications in rat liver DNA and RNA including increases in
      8-oxoguanine and the formation of 8-aminoguanine. We compared the levels of these
      modifications in the two animal species at 6, 18 and 42 h after a single i.p.
      treatment with 1.12 mmol/kg 2-NP. Significantly less nucleic acid base
      modifications were found to be produced in rabbit liver than in rat liver. Thus,
      the relative resistance of the rabbit to the hepatocarcinogenicity of 2-NP
      correlates with decreased levels of 2-NP-induced liver DNA and RNA base damage.

PMID- 7506991
TI  - Inhibition of tumor cell-induced angiogenesis by retinoids, 1,25-dihydroxyvitamin
      D3 and their combination.
AB  - Tumor-induced angiogenesis (TIA), i.e., the ability of transformed cells to
      stimulate new blood vessel formation is an important factor contributing to tumor
      growth and invasiveness. The antiangiogenic effect of the retinoids, all-trans
      retinoic acid, 13-cis retinoic and 9-cis retinoic acid, of 1,25-dihydroxyvitamin
      D3, and of their combinations were studied using an experimental system in vivo.
      TIA was induced in immunosuppressed mice by intradermal injection of the two
      human transformed keratinocyte lines, Skv-e2, harboring DNA of human
      papillomavirus (HPV) type 16, and HeLa, harboring HPV18 DNA. The three retinoids
      and 1,25-dihydroxyvitamin D3, when administered systemically to mice, before the
      angiogenesis assay significantly decreased TIA. Their combination led to a
      synergistic inhibition of TIA. These results provide the basis for the use of
      combination of retinoids and 1,25-dihydroxyvitamin D3 in treatment of neoplastic
      diseases.

PMID- 7506992
TI  - The majority of nitric oxide synthase in pig heart is vascular and not neural.
AB  - OBJECTIVE: As a physiological mediator of smooth muscle relaxation and possibly a
      non-adrenergic non-cholinergic (NANC) neurotransmitter, nitric oxide plays a role
      in regulating coronary artery blood flow and modulating myocardial contractility.
      Although recent attention has been directed toward neural tissue, we investigated
      the possibility that vessels, as well as nerves, may be a source of nitric oxide
      in the heart. METHODS: The NADPH-diaphorase method was used to localise the
      synthesis enzyme, nitric oxide synthase (NOS), in the pig heart. RESULTS: All
      regions showed a similar staining pattern. Muscle fibres had virtually no NOS
      activity. The endocardium showed reaction product in a lattice configuration
      without much cytoplasmic staining, suggesting that endothelial cell membranes are
      the primary site of NOS activity. Every vessel contained reaction product in
      intima but none in the media or adventitia. Muscular arteries had more NOS
      activity than veins. Lighter staining capillaries coursed along each muscle
      fibre. Only a few scattered nerve processes and rare neuronal cell bodies with
      NOS activity were present in the heart; there was no particular spatial
      relationship between neural tissue and vessels. CONCLUSIONS: (1) the majority of
      NOS activity in the pig heart is in vascular endothelium, consistent with the
      concept of nitric oxide as a regulator of coronary blood flow; less is present in
      the endocardium; (2) paucity of nerves with NOS activity probably indicates that
      this particular type of NANC neural tissue does not affect coronary blood flow
      directly; and (3) although muscle fibres have no discernible NOS activity, the
      rich vascular supply in close proximity may subserve some myocardial function of
      nitric oxide.

PMID- 7506993
TI  - An introduction to the jargon of molecular biology. Part II.

PMID- 7506995
TI  - Regulation of the arabidopsis floral homeotic gene APETALA1.
AB  - The Arabidopsis floral homeotic gene APETALA1 (AP1) encodes a putative
      transcription factor that acts locally to specify the identity of the floral
      meristem and to determine sepal and petal development. RNA tissue in situ
      hybridization studies show that AP1 RNA accumulates uniformly throughout young
      floral primordia, but is absent from the inflorescence meristem. Later in
      development, AP1 RNA is excluded from cells that will give rise to the two inner
      whorls of organs. Here we show that AP1 expression is under the control of two
      negative regulators: the meristem identity gene TERMINAL FLOWER represses AP1 RNA
      accumulation in the inflorescence meristem, and the organ identity gene AGAMOUS
      prevents AP1 RNA accumulation in the two inner whorls of wild-type flowers. These
      and other data presented here lead to a revised model for the regulatory
      interactions among the genes specifying floral organ identity in Arabidopsis.

PMID- 7506994
TI  - Nitric oxide release from porcine mitral valves.
AB  - OBJECTIVE: The aim was to investigate the release of nitric oxide (NO) from
      porcine mitral valves. METHODS: The valves were sandwiched between gauze in a
      chamber constantly perfused by Holman solution. The presence of NO in the
      perfusate of the valves was detected by two methods: a bioassay cascade system
      using preconstricted rings of pig coronary artery as the detector tissue, and a
      chemiluminescent method, specific for NO. RESULTS: Porcine mitral valves release
      NO under basal conditions. Release can be increased by the agonists ADP,
      substance P, bradykinin, thrombin, and the calcium ionophore A23187. ADP was by
      far the most effective. NO release under basal conditions was inhibited by each
      of the three NO synthase inhibitors studied, but only NG-monomethyl-L-arginine (L
      NMMA) reduced ADP stimulated release. A reversible inhibition of NO release
      occurred when valves were perfused with calcium-free Holman solution and NO
      release was inhibited by removal of the endocardial monolayer. CONCLUSIONS: The
      endocardial endothelium covering the mitral valves releases NO under basal
      conditions and following stimulation with several agonists. The NO synthase
      enzyme is calcium dependent. Different mechanisms may exist for the synthesis of
      basal and agonist dependent NO release in these cells.

PMID- 7506996
TI  - The three-dimensional structure of H-2Db at 2.4 A resolution: implications for
      antigen-determinant selection.
AB  - Solution at 2.4 A resolution of the structure of H-2Db with the influenza virus
      peptide NP366-374 (ASNEN-METM) and comparison with the H-2Kb-VSV (RGY-VYQGL)
      structure allow description of the molecular details of MHC class I peptide
      binding interactions for mice of the H-2b haplotype, revealing a strategy that
      maximizes the repertoire of peptides than can be presented. The H-2Db cleft has a
      mouse-specific hydrophobic ridge that causes a compensatory arch in the backbone
      of the peptide, exposing the arch residues to TCR contact and requiring the
      peptide to be at least 9 residues. This ridge occurs in about 40% of the known
      murine D and L allelic molecules, classifying them as a structural subgroup.

PMID- 7506997
TI  - T cell-derived antigen-specific humoral immune response. II. Further
      characterization of the response and the antigen binding T cell immunoproteins.
AB  - Murine T lymphocyte-derived proteins which bind nominal antigen specifically
      (TABM) were detected in serum during a humoral immune response to bovine serum
      albumin. The TABM response was observed only when the adjuvants
      polyadenylic:polyuridylic acid complex (poly(A: U)), Freund's complete adjuvant
      or Titermax were used concurrently with antigen to immunize. When poly(A:U) was
      used, higher doses of antigen were optimal to stimulate TABM production than
      those required to stimulate immunoglobulin production. The binding of TABM in the
      serum of BSA-immunized mice to BSA in solid phase was inhibited specifically by
      10-fold more BSA than that required to inhibit BSA-specific immunoglobulins
      suggesting that TABM have much less affinity for antigen than immunoglobulins.
      Immunoblotting of TABM in serum from BSA-immune mice, which bind BSA,
      demonstrated that these serum TABM are comprised of M(r) 110,000 polypeptides
      linked by disulfide bonds. Antigen-specific proteins in a lysate of an NP
      specific T cell hybrid inhibited the recognition of serum TABM by anti-TABM
      antiserum while a lysate of a B cell hybridoma was not inhibitory, and serum TABM
      were adsorbed by monoclonal antibodies to TCR-C beta. These results provide more
      evidence that serum TABM may be a soluble analogue of the T cell receptor for
      antigen.

PMID- 7506998
TI  - Pathways of signaling in nonspecific cytotoxic cells: effects of protein kinase
      and phosphatase inhibitors and evidence for membrane tyrosine phosphorylation.
AB  - The present study was done to examine the role of protein kinases (PK) and
      phosphatases in nonspecific cytotoxic cell (NCC) activation processes. Treatment
      of NCC with 30 or 60 microM H-7 prior to adding IM-9 target cells significantly
      inhibited cytotoxicity. A similar concentration and time-dependent inhibition
      response was observed following treatment with H-8. The calcium and cyclic
      nucleotide antagonist HA1004, however, produced a significant increase in
      cytotoxicity at 30 and 60 microM concentrations. Treatment with genistein
      produced almost 100% inhibition of NCC lysis of IM-9 targets at a 142
      micrograms/ml concentration. Studies were also carried out to determine the
      effects of these cytotoxicity modulators on stimulus-induced responses. In all
      cases where the costimulus consisted of the calcium ionophore A23187,
      cytotoxicity was markedly increased. In experiments using subsaturating
      concentrations of mab 5C6 as the costimulus, genistein completely reversed
      (inhibited) the modulating effects of this mab. Additional evidence for protein
      phosphorylation was obtained by immunoprecipitation and Western blot analysis
      (using antiphosphotyrosine mab 4G10) of membranes from mab 5C6-stimulated NCC.
      The role of protein phosphorylation on cytotoxic activity was further analyzed by
      the use of phosphatase inhibitors. Preincubation of NCC with either sodium
      orthovanadate or sodium fluoride significantly increased cytotoxicity. Lithium
      chloride had little or no effect on the killing of IM-9 target cells. These data
      indicate that multiple second messenger pathways participate in NCC lytic
      responses, the most crucial of which appears to facilitate phosphorylation of
      tyrosine residues on membrane proteins.

PMID- 7506999
TI  - Structural requirements for recognition of a type II collagen peptide by murine T
      cell hybridomas.
AB  - T lymphocytes play a critical role in the development of murine collagen-induced
      arthritis (CIA), a syndrome which shares many features with rheumatoid arthritis.
      In susceptible mouse strains, immunization with type II collagen (cII) results in
      chronic inflammation with progressive joint destruction. To examine T cell
      recognition of cII we have isolated T cell hybridomas specific for a cII peptide
      fragment, cII260-270 (IAGFKGEQGPK). We assessed the importance of particular
      amino acid residues to formation of the MHC Class II-peptide complex and
      interaction of this complex with TCRs. Our results indicate that critical
      residues are concentrated in the N-terminal half of the peptide, with Lys264 and
      Glu266 having the greatest influence. Replacement of these residues with alanine
      resulted in loss of detectable activity. Three other residues, Ile260, Gly262,
      and Phe263, are also important to T cell stimulation because alanine substitution
      substantially decreased peptide activity. Truncation analyses supported the
      conclusion drawn from Ala substitutions that C-terminal residues were
      dispensable. Other alterations in peptide structure resulted in dramatic
      increases in stimulatory capacity. For example, replacement of either Gly265 or
      Gly268 with alanine resulted in a 10-fold increase in potency. The addition of 2
      5 residues to the N-terminus of the peptide decreased the dose required for
      maximal T cell stimulation by > 100-fold. The T cell hybridomas exhibited
      remarkable similarity in their peptide recognition profiles although they express
      different TCR V beta elements.

PMID- 7507000
TI  - Anti-Fas antibody induces different types of cell death in the human histiocytic
      cell line, U937, and the human B cell line, B104: the role of single-strand DNA
      breaks and poly (ADP-ribosyl)ation in cell death.
AB  - We investigated the anti-Fas antibody-induced cell death in two different types
      of human cell lines, U937 and B104. IFN-gamma increased the surface expression of
      Fas antigen and susceptibility to anti-Fas Ab-induced cell death of B104 and U937
      cells. Anti-Fas Ab-induced death of U937 and B104 cells required neither a Ca2+
      influx nor macromolecular synthesis. U937 cells treated with anti-Fas Ab
      represented apoptosis with DNA fragmentation, whereas anti-Fas Ab-treated B104
      cells did not. Single-strand DNA breaks, however, appeared in the B104 cells.
      Zinc ions prevented DNA fragmentation and the morphological features of apoptosis
      in anti-Fas Ab-treated U937 cells, but did not inhibit cell death. However, zinc
      ions, when used in combination with the poly(ADP-ribosyl)ation inhibitors,
      inhibited anti-Fas Ab-induced U937 cell death. The inhibitors by themselves did
      not inhibit anti-Fas Ab-induced U937 cell death, but did inhibit anti-Fas Ab
      induced B104 cell death. A substantial decrease in NAD pools was observed in anti
      Fas Ab-treated B104 and U937 cells in parallel with the increase of DNA strand
      breaks before cell death became apparent. These results suggest the involvement
      of single-strand DNA breaks and poly(ADP-ribosyl)ation in the mechanisms of anti
      Fas Ab-induced U937 and B104 cell death.

PMID- 7507001
TI  - Preferential but not exclusive T cell receptor V beta chain utilization of myelin
      basic protein and peptide-specific T cell clones in mice.
AB  - The repertoire of T cell receptor (TCR) V beta chain utilization was investigated
      in PL/J, CXJ-1, SJL/J and B10.S-->SJL/J chimeric mice in response to either
      myelin basic protein (MBP) or the strain-specific encephalitogenic peptide. Our
      analysis showed that there was an overlapping predominance in the TCR V beta gene
      utilization in the MBP-specific responses, which were independent of the major
      histocompatibility complex (MHC) class II haplotype present, and the
      immunodominant peptide region recognized in these different strains. In those
      mice having the TCR V beta b haplotype (PL/J, CXJ-1, and the B10.S-->SJL chimera)
      either the TCR V beta 4, 8, and 13 or the TCR V beta 4, 6, and 13 predominated.
      In contrast, in mice with TCR V beta a haplotype (SJL/J) V beta 4, 6, and 17a
      were found. However, the quantitative distribution of these preferentially
      utilized TCR V beta chains in each strain was defined by the MHC class II
      haplotype and the immunodominant peptide recognized. The expression of the V beta
      8 gene product in the peripheral TCR repertoire did not always correlate with
      predominant V beta 8 utilization in the MBP-specific response.

PMID- 7507002
TI  - IL-7 induces surface expression of B7/BB1 on pre-B cells and an associated
      increase in their costimulatory effects on T cell proliferation.
AB  - Treatment with IL-7 of NALM-6 pre-B cells, but not of EBV-LCL, Daudi, HeLa, or
      K562 cells resulted in enhanced costimulatory activity for TSST-1-induced T cell
      proliferation. The effect of IL-7 on the costimulatory function of NALM-6 cells
      was dose-dependent, could be inhibited by a neutralizing anti-IL-7 mAb, and
      resulted in the need of less costimulatory cells, or less superantigen, to obtain
      proper T cell proliferation. Addition of anti-IL-7 mAb to the coculture of
      superantigen-stimulated T cells with IL-7-pretreated NALM-6 cells did not alter
      the T cell responses obtained without addition of this antibody. These findings
      suggest that a possible costimulation of T cells by surface-bound IL-7 on
      pretreated NALM-6 cells did not contribute to the enhanced costimulatory function
      observed. Rather, these studies implicate IL-7-induced alterations of the NALM-6
      cells themselves as the basis for the enhanced costimulatory activity observed.
      The most remarkable phenotypic differences between efficient costimulatory B
      lineage cells and deficient pre-B cells are a lower expression of ICAM-1 (CD54)
      and a lack of expression of the costimulatory B cell activation antigen B7/BB1.
      Upon activation with IL-7, the expression of ICAM-1 was increased, and the
      expression of B7/BB1 antigens was induced. The increased T cell responses in the
      presence of IL-7-treated NALM-6 cells could be inhibited by addition of anti-BB1
      mAb. These results suggest that B7/BB1-negative pre-B cells may acquire the
      surface expression of B7/BB1 upon stimulation with IL-7, a process which is
      associated with increased costimulatory function for T cell proliferation.

PMID- 7507003
TI  - Up-regulation of a thymic epithelial ligand after contact with thymocytes.
AB  - Thymic medullary epithelial cells of the E-5 line were shown to form in vitro
      complexes with thymocytes resulting in no apparent modification to the thymocytes
      participating in the complex, but in tyrosine phosphorylation on a glycoprotein
      associated with the epithelial adhesion molecule. Because signal transduction
      from lymphocytes to stromal cells is poorly documented, we examine in this work
      events which follow epithelial cell activation. Our findings indicate that one
      chain of the epithelial adhesion molecule (gp23), after complex formation with
      thymocytes, undergoes a rapid and transient tyrosine kinase-dependent up
      regulation.

PMID- 7507007
TI  - Improved procedures for enzyme immunoassay of tacrolimus (FK506) in whole blood.

PMID- 7507006
TI  - Endocrine causes of impotence.

PMID- 7507004
TI  - Immune responses to bacterial polysaccharides: terminal epitopes are more
      immunogenic than internal structures.
AB  - Two types of dextran-protein conjugates can be produced depending on the size of
      dextran and the method chosen for coupling. Dextran of 4 x 10(4) molecular
      weight, randomly coupled to keyhole limpet hemocyanin evoked "incomplete" T cell
      dependent (TD) immune responses. This atypical response only affected the dextran
      epitope since the response to the protein carrier was as expected for TD
      secondary immune responses. A second type of TD conjugates can be derived by
      coupling dextran (Dx) of 10(3) Da to the protein chicken serum albumin (CSA) via
      the reducing end (CSA-Dx-1). Immunization with CSA-Dx-1 induced the classical
      pattern of TD immune responses. Interestingly, immunization with CSA-Dx-1 favored
      the production of antibodies directed against terminal structures of the dextran
      molecule. These results were also confirmed at the hybridoma cell level. In
      contrast to other protein-dextran conjugates, CSA-Dx-1 was able to induce anti
      dextran antibodies in CBA/N mice and in neonatal animals. We have interpreted
      these results to mean that conjugates exposing carbohydrate terminal nonreducing
      end structures could be more "physiological" and able to be recognized by helper
      T cells. This opens a new possibility for the production of vaccines against
      bacterial polysaccharides.

PMID- 7507005
TI  - Functional and phenotypic characterization of WC1+ gamma/delta T cells isolated
      from Babesia bovis-stimulated T cell lines.
AB  - Functional studies with WC1+ gamma/delta T cell lines were performed to clarify
      the role of this subpopulation of gamma/delta T cells in the in vitro immune
      response to Babesia bovis. As CD4+ T cells decreased and gamma/delta T cells
      increased in B. bovis-stimulated T cell lines, antigen-specific proliferation
      declined to background levels. One irradiated gamma/delta T cell line inhibited
      proliferation of autologous Th1 cells, although unirradiated gamma/delta T cells
      either synergized with or had no effect on Th cell proliferation. gamma/delta T
      cells were not cytolytic for bovine alpha/beta T cells, but expressed natural
      killer (NK)-like cytotoxicity when assayed on xenogeneic NK-sensitive target
      cells. The gamma/delta T cells were IL-2 dependent and expressed IFN-gamma and
      TNF-alpha, but not TNF-beta, IL-2, or IL-4 mRNA. Together, these results raise
      the possibility that WC1+ gamma/delta T cells respond in vitro to autoantigens
      present on CD4+ T cells or to cytokines secreted by activated CD4+ T cells,
      resulting in modulation of the CD4+ T cell response and outgrowth of the
      gamma/delta T cells in parasite-stimulated lines.

PMID- 7507008
TI  - Serotonin, catecholamines, histamine, and their metabolites in urine, platelets,
      and tumor tissue of patients with carcinoid tumors.
AB  - We monitored long-term (median 11 months) concentrations of platelet serotonin
      and urinary serotonin, 5-hydroxyindoleacetic acid, and seven catecholamine
      metabolites in 44 patients with carcinoid tumors. Tumor serotonin and
      catecholamine contents (11 patients) and urinary histamine and N-methylhistamine
      (15 patients) were determined. Consistently increased concentrations of indoles,
      notably platelet serotonin, were observed in 96%, 43%, and 0% of patients with
      mid-, fore-, and hindgut carcinoids, respectively. Urinary dopamine metabolites,
      notably 3-methoxytyramine, were consistently increased in 38%, 20%, and 7% of
      patients with mid-, hind-, and foregut carcinoids, respectively. For urinary
      norepinephrine/epinephrine metabolites, notably normetanephrine and metanephrine,
      these data were 33%, 20%, and 14%, respectively. Midgut carcinoid tumors had the
      highest serotonin contents, whereas concentrations of catecholamines were
      independent of primary localization. There was no consistent relation between
      biogenic amine contents in tumors and urinary excretion of the amine metabolites.
      Occurrence of carcinoid syndrome was related to increased serotonin production
      rate. Increased histamine production is not an important feature in patients with
      lung carcinoids or liver-metastasized ileum carcinoids.

PMID- 7507009
TI  - Growth hormone dose regimens in adult GH deficiency: effects on biochemical
      growth markers and metabolic parameters.
AB  - OBJECTIVE: We examined the effects of different doses of GH on insulin-like
      growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3), body composition,
      energy expenditure, and various metabolites in GH deficient adults, in order to
      approach a metabolically appropriate GH dosage in young GH deficient adults.
      DESIGN: Ten GH deficient patients (age 21-43) were studied after 4 weeks without
      GH followed by three consecutive 4-week periods, where the patients received in a
      fixed order GH 1, 2 and 4 IU/m2 s.c. per day. At the end of each period the
      patients were hospitalized for a 24-hour examination. RESULTS: Mean 24-hour
      levels of GH (mIU/l) were 2.7 +/- 0.3 (0 GH), 7.2 +/- 0.9 (1), 10.8 +/- 1.5 (2)
      and 18.9 +/- 2.7 (4 IU/m2) (mean +/- SEM) (P < 0.01). Likewise, IGF-I levels
      increased dose dependently from 61 +/- 21 to 206 +/- 65, 260 +/- 70 and 468 +/-
      171 micrograms/l (P < 0.05); serum IGF-I in an age and sex matched control group
      was 248 +/- 25 micrograms/l. Corresponding serum IGFBP-3 levels also increased
      from 1860 +/- 239 to 3261 +/- 379, 3762 +/- 434 and 4384 +/- 652 micrograms/l (P
      = 0.01) respectively. Significant increases in diurnal serum insulin levels after
      4 IU/m2 were recorded, whereas plasma glucose levels remained unchanged. Lipid
      intermediates increased dose independently during GH administration. GH caused a
      significant increase in resting energy expenditure, whereas the respiratory
      exchange ratio was unaltered. Fat mass was increased without GH therapy and
      decreased during the study. Four patients made complaints during 4 IU/m2 GH
      administration, probably related to GH induced fluid retention. CONCLUSION: Based
      primarily on IGF-I and IGFBP-3 levels our data suggest that a GH replacement dose
      in young GH deficient adults in the order of 1-2 IU/m2 per day is adequate. This
      is a relatively low dose as compared to dose regimens in children and
      adolescents.

PMID- 7507010
TI  - Plasma IGFBP-3 and its relationship with quantitative growth hormone secretion in
      short children.
AB  - OBJECTIVE: We assessed the relationship between serum IGFBP-3 levels with IGF-I
      and quantitative GH secretory status in poorly growing children. DESIGN: We
      studied the relationship between 24-hour integrated concentration of GH, peak GH
      to paired sequential stimulation tests, IGF-I and the IGFBP-3 serum levels.
      PATIENTS: One hundred and two children (82 males, 20 females, age 11.7 +/- 2.7
      years) with short stature (height -2.6 +/- 0.7 SDS) were studied. MEASUREMENTS:
      Quantitative GH secretory status was assessed by the 24-hour integrated GH and by
      response to arginine and insulin stimulation. GH, IGFBP-3 and IGF-I were measured
      by radioimmunoassay. To adjust for age and gender, IGFBP-3 levels were converted
      to SD score. RESULTS: IGFBP-3 SDS was strongly correlated with IGF-I SDS (r =
      0.64, P < 0.0001), and weakly with peak GH (r = 0.28, P < 0.0004), but not with
      the integrated GH concentration (r = 0.07, P < 0.46). IGFBP-3 SDS increased with
      pubertal maturation (P < 0.0001). There was no difference in mean IGFBP-3 SDS in
      subgroupings of the patients based on the results of their quantitative GH tests.
      CONCLUSION: In short children, IGFBP-3 levels increase with puberty, are strongly
      correlated with IGF-I levels, weakly correlated with peak response to GH
      stimulation tests, but not correlated with integrated GH. Consequently,
      diagnostic classifications of patients based on quantitative measurements of GH
      secretion and IGFBP-3 differ.

PMID- 7507011
TI  - Neonatal capsaicin pretreatment suppresses intramedullary inflammation in
      adjuvant-induced spondylitis.
AB  - In order to investigate the proposed involvement of neuropeptides in
      musculoskeletal inflammation we pretreated rats, in an adjuvant spondylitis
      model, with capsaicin, a neurotoxin. Immunohistochemistry showed that
      administration of capsaicin to newborn rats depleted irreversibly the
      neuropeptide, substance P. Elimination of capsaicin-sensitive fibres by the
      neonatal injection of capsaicin did not suppress the peridiscitis of rats in
      which adjuvant spondylitis was induced at 7 weeks of age. However, elimination of
      capsaicin-sensitive fibres did suppress the inflammation usually seen in the bone
      marrow. We speculate that this intramedullary inflammation is normally induced or
      sustained by capsaicin-sensitive fibres.

PMID- 7507013
TI  - Regulation of human basophil activation; the role of Na+ and Ca2+ in IL-3-induced
      potentiation of IgE-mediated histamine release from human basophils.
AB  - The release of mediators from human basophils is strongly enhanced by IL-3.
      However, the signalling pathways of IL-3 are poorly defined in these cells. Since
      external Ca2+ and Na+ play important regulating roles in histamine release, the
      possibility that these cations could be involved in the potentiation by IL-3 of
      the anti-IgE-induced histamine release from human basophils was considered, and
      it was observed that: (i) IL-3 dramatically decreased the external Ca2+
      requirement for IgE-mediated histamine release. However, histamine release from
      IL-3-treated basophils became only partially independent of external Ca2+, since
      addition of EGTA in the external medium abolished the effect of IL-3; (ii)
      decreasing Na+ influx by lowering external Na+ concentration in isosmotic medium
      inhibited the potentiating effect of IL-3 on IgE-mediated release; (iii)
      amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchanges, and its derivative,
      benzamil, more specific for Na+/Ca2+ exchanges, inhibited the release potentiated
      by IL-3. In contrast, the amiloride derivative 5-(N,N-dimethyl)-amiloride, more
      specific for Na+/H+ exchanges, slightly increased the IL-3-enhanced release.
      Thus, the decreased requirement for external Ca2+ and the dependence on external
      Na+, taken with the effect of the Na+/Ca2+ exchange inhibitors, suggest that
      Na+/Ca2+ exchanges are involved in the IL-3-induced enhancement of IgE-mediated
      human basophil histamine release.

PMID- 7507012
TI  - MHC class I, MHC class II and intercellular adhesion molecule-1 (ICAM-1)
      expression in inflammatory myopathies.
AB  - We investigated the relationship between the MHC-I, MHC-II and intercellular
      adhesion molecule-1 (ICAM-1) expression on myofibres and the presence of
      inflammatory cells in muscle specimens of 18 patients with inflammatory
      myopathies (nine polymyositis, seven dermatomyositis, two inclusion body
      myositis). We observed MHC-I expression in muscle fibres, infiltrating
      mononuclear cells and endothelial cells in every specimen. In seven patients,
      some muscle fibres were MHC-II-positive for the DR antigen, while the DP and DQ
      antigens were absent. ICAM-1 expression, detected in seven patients, was found in
      clusters of myofibres, associated with a marked MHC-I positivity and a widespread
      mononuclear infiltration. Most of the ICAM-1-positive fibres were regenerating
      fibres. Furthermore, some fibres expressed both ICAM-1 and DR antigens near
      infiltrating cells. This finding could support the hypothesis that myofibres may
      themselves be the site of autosensitization.

PMID- 7507014
TI  - Peripheral T lymphocyte depletion by apoptosis after CD4 ligation in vivo:
      selective loss of CD44- and 'activating' memory T cells.
AB  - We have demonstrated that a single intravenous bolus of rat anti-CD4 MoAb caused
      a small but prolonged increase in apoptosis in murine lymph nodes. We have
      quantified this process using the novel Highly Optimized Microscope Environment
      (HOME) interactive images analysis system and shown that the increase in
      apoptosis was sufficient to account for the observed depletion of the peripheral
      CD4+ T cell subset. This occurred in the absence of any other exogenous signal.
      Furthermore, there was no evidence of an inflammatory or necrotic response in the
      tissues, indicating that this was unlikely to be Fc or complement-mediated
      antibody killing. The anti-CD4-induced depletion selectively removed CD44- T
      cells. Using mice previously immunized with yeast-derived HIV-1 p24 recombinant
      protein there was sparing of memory T cell function after in vivo anti-CD4
      treatment, except during a window of less than 24 h duration, when simultaneous
      exposure to antigen and anti-CD4 antibody resulted in the depletion of specific
      memory T lymphocyte function. This indicated that a very minor alteration in the
      frequency of apoptosis had a marked effect on cell number over time, and
      suggested that opportunistic infection associated with CD4+ T cell depletion may
      be explained by loss of memory cells when there is antigenic stimulation at the
      same time as CD4 ligation. These results have implications for the pathology of
      HIV-associated disease which is associated with ligation of CD4 molecules in
      vivo.

PMID- 7507015
TI  - Immunopathological features of palatine tonsil characteristic of IgA nephropathy:
      IgA1 localization in follicular dendritic cells.
AB  - IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular
      deposition of circulating immune complexes containing IgA as the major antibody
      component. Upper respiratory infections and tonsillitis often precede IgAN, and
      in some cases tonsillectomy is effective for the treatment of IgAN. Thus, the
      tonsil seems to be a unique organ causing initial and/or progressive events to
      generate nephritogenic immune complexes in IgAN. In this study we focused on the
      analysis of immunopathological features of the palatine tonsil characteristic of
      IgAN patients by using an immunohistochemical technique. The IgA1 subclass was
      demonstrated in follicular dendritic cells (FDC) of the tonsil of IgAN patients,
      but not in FDC of non-IgAN controls. On the other hand, IgA2, IgG, IgM and C3 did
      not show any differences in distribution between the two groups. Moreover, the
      expression of decay-accelerating factor (DAF), an inhibitor of homologous
      complement activation, and transforming growth factor-beta 1 (TGF-beta 1), an
      inducer of antibody-producing cells to IgA class switching, in FDC and
      interdigitating dendritic cells of the tonsil, respectively, which was also
      clarified in this study for the first time, was found to be identically
      distributed in the two groups. These findings may support the idea that IgA1,
      possibly in an immune complex form, is trapped by FDC and plays an important role
      in the persistent activation of particular B cell repertoires responsible for the
      onset and/or progression of IgAN.

PMID- 7507016
TI  - Soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of disease
      relapse in idiopathic uveoretinitis.
AB  - This study reports the results of a point prevalence study of markers of
      endothelial dysfunction in the serum of patients with idiopathic uveoretinitis.
      sICAM-1, soluble endothelial leucocyte adhesion molecule (sELAM), anti
      endothelial cell antibodies (AECA) and von Willebrand factor (vWF) levels were
      measured in 32 patients with isolated idiopathic uveoretinitis and seven with
      uveitis in association with systemic disease, using commercial and in-house
      ELISAs. Raised levels of AECA were found in 31% of patients with isolated
      uveitis, vWF in 28%, sELAM in 15.6% and sICAM-1 in 31%. Further analysis revealed
      that raised sICAM-1 levels were closely associated with recent relapse of disease
      (P = 0.00003). Patients with accompanying systemic disease were found to have a
      similar prevalence of these serum abnormalities to those with isolated ocular
      disease. In conclusion, vascular endothelial dysfunction may contribute to
      pathogenesis in uveoretinitis, and in particular sICAM-1 may prove a marker of
      disease relapse in this condition.

PMID- 7507017
TI  - Renal tubular protein degradation of radiolabelled aprotinin (Trasylol) in
      patients with chronic renal failure.
AB  - 1. The new method developed to measure renal tubular degradation of small
      filtered proteins in patients with normal renal function, using radiolabelled
      aprotinin (Trasylol) (R. Rustom, J. S. Grime, P. Maltby, H. R. Stockdale, M.
      Critchley, J. M. Bone. Clin Sci 1992; 83, 289-94), was evaluated in patients with
      chronic renal failure. 2. Aprotinin was labelled with either 99mTc (40 MBq) or
      131I (0.1 MBq), and injected intravenously in nine patients, with different renal
      pathologies. 51Cr-EDTA clearance (corrected for height and weight) was 40 +/- 5.4
      (range 11.2-81) ml min-1 1.73 m-2. Activity in plasma and urine was measured over
      24-48 h, and chromatography on Sephadex-G-25-M was used to separate labelled
      aprotinin from free 99mTcO4- or 131I-. Renal uptake was measured for 99mTc
      labelled aprotinin only. 3. The volume of distribution was 20.2 +/- 2.3 litres.
      Chromatography showed all plasma activity as undegraded aprotinin, and urine
      activity only as the free labels (99mTcO4- or 131I-). 4. As in patients with
      normal renal function, activity in the kidney appeared promptly, with 5.7 +/-
      2.5% of the dose detected even at 5 min. Activity rose rapidly to 9.4 +/- 1.6% of
      dose after 1.5 h, then more slowly to 15.0 +/- 0.5% of dose at 4.5 h, and even
      more slowly thereafter, reaching 24.1 +/- 2.8% of dose at 24 h. Extra-renal
      uptake was again insignificant, and both 99mTcO4- and 131I- appeared promptly in
      the urine, with similar and uniform rates of excretion over 24 h.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7507019
TI  - On describing the psychological struggle of child sexual abuse victims through
      Kierkegaard's concept of self.
AB  - The aim of this paper is to use Soren Kierkegaard's concept of self to
      demonstrate some psychological phenomena of child sexual abuse victims. Their
      self is to a large extent determined by extreme outer circumstances i.e. the
      abuse and the abusers. In order to cope with the consequent psychological pain,
      such children employ powerful defense mechanisms which consequently, however,
      means that they remain longer in the abuse. Psychotherapies are attempts to help
      them to create their own self and gradually come out of their abuse. However,
      such creation of oneself is only carried out within their concretely traumatized
      self.

PMID- 7507020
TI  - Rumination: the eating disorder of infancy.
AB  - Rumination is a relatively rare, potentially fatal syndrome in infants. This
      article reviews the historical and current treatment of rumination. Two cases are
      presented: a six-month-old who narrowly escaped surgery when the disorder was not
      recognized, and a complicated case from the neonatology intensive care unit.
      Environmental changes and enhanced mothering are described as being critical to
      correction of rumination and appropriate weight gain.

PMID- 7507018
TI  - Biodevelopmental aspects of conduct disorder in boys.
AB  - The association between biochemical parameters and conduct disorder (CD) was
      studied in 22 boys admitted to a residential center. Three-methoxy-4
      hydroxyphenylglycol (MHPG) levels were significantly higher in prepubertal CD
      youth than in pubertal/post pubertal CD youth. Homovanillic acid (HVA) levels
      were significantly lower in CD youth under age 12.0 years than in non CD youth
      under age 12.0 years. The implications of these biodevelopmental findings in the
      study of CD are discussed.

PMID- 7507021
TI  - Detection of HCV infection by cPCR in patients with acute leukemia.
AB  - HCV RNA and anti-HCV were detected respectively by complemented DNA polymerases
      chain reaction (cPCR) and ELISA in the sera of 28 acute leukemia patients with
      repeated blood transfusion and changes in liver function. HCV RNA positive rate
      was 78.6%. Anti-HCV positive rate was 60.7%. 25 subjects showed positive results
      in HCV RNA or anti-HCV, or in both of them. By combined assessment, the HCV
      infection rate was 89.3%. Acute leukemia patients were the high risk group of HCV
      infection because of the lowered immune function and repeated blood transfusion.
      By cPCR, HCV RNA can be detected earlier and the sensitivity is higher than by
      anti-HCV. So cPCR is a sensitive and specific method for early diagnosis of HCV
      infection. The combination of HCV RNA and anti-HCV detection methods may improve
      the diagnostic rate of HCV infection.

PMID- 7507022
TI  - Automatic lineage assignment of acute leukemias by flow cytometry.
AB  - A method for automatic lineage assignment of acute leukemias was developed. Input
      are eight list mode data files acquired with a FACScan flow cytometer. For each
      cell, four parameters are measured: forward light scatter, orthogonal light
      scatter, fluorescein fluorescence, and phycoerythrin fluorescence. Eight data
      files are acquired in the following sequence: unstained, isotype controls,
      CD10/CD19, CD20/CD5, CD3/CD22, CD7/CD33, HLADR/CD13, and CD34/CD38. First, each
      of the data files 3 to 8 are clustered independently employing an algorithm based
      on nearest neighbors. Next, the clusters are associated across the data files to
      form cell populations, using the assumption of light scatter invariance across
      tubes for each population. The mean positions of each cell population are fed
      into a decision tree. The decision tree first identifies normal cell populations,
      i.e., monocytes, neutrophils, eosinophils, basophils, NK cells, T-lymphocytes,
      and B-lymphocytes. After elimination of the normal cell populations from the data
      space, the residual cell populations are classified as B-lineage ALL, T-lineage
      ALL, AML, AUL, B-CLL, or unknown. The effectiveness of this novel approach is
      shown with case studies of B-lymphoid, T-lymphoid, and Myeloid acute leukemias.

PMID- 7507024
TI  - Rapid method for cell cycle analysis in a predatory marine dinoflagellate.
AB  - Oxyrrhis marina (Dujardin) is a predatory marine dinoflagellate that feeds
      phagocytically on live phytoplanktonic "prey" cells from the surrounding
      environment. A rapid method was developed to separate the cell cycle
      characteristics of these predators from their prey cells in order to study the
      cell cycle dynamics of this organism. Nuclei from Oxyrrhis were isolated in low
      salt buffer (PBS) using detergent and mechanical agitation and the DNA stained
      with Hoechst 33258 in a one step procedure. The method permitted the isolation of
      nuclei from the Oxyrrhis cells with > 95% efficiency. Discrimination between prey
      cell nuclei and those of Oxyrrhis was achieved during flow cytometric analysis
      which yielded routinely G1 CVs of 3-6% for exponentially growing cell populations
      and 2-3% for stationary phase cells. The method was used to demonstrate the
      changes in cell cycle dynamics during the exponential and stationary phases of
      growth. Results indicated that in contrast to most mammalian and phytoplankton
      cell types Oxyrrhis spent the major portion (ca. 50%) of its cell cycle in G2 + M
      when actively dividing. Analysis of stationary phase populations also suggests
      that specific cell cycle control (or restriction) points were present in both G1
      and G2 in this species.

PMID- 7507023
TI  - Identification and quantitation of apoptotic cells following anti-CD3 activation
      of murine G0 T cells.
AB  - Multiparameter flow cytometry and cell sorting were used to examine the process
      of apoptosis after activation of murine resting T cells with immobilized anti
      CD3. Activated T cells treated with Hoechst 33342 (HO-33342) and analyzed by flow
      cytometry showed two major cell populations of high and low fluorescence. These
      populations were sorted and the DNA extracted and subjected to electrophoresis.
      Electrophoresis of DNA extracted from T cells showing a low level of HO-33342
      fluorescence (HO-Low) resulted in a typical ladder pattern characteristic of
      internucleosomal DNA degradation associated with apoptosis, whereas the cellular
      DNA of the cells showing a high level of fluorescence (HO-High) showed a narrow
      high molecular weight band. Multiparameter analysis further indicated that cells
      with HO-High characteristics possessed corresponding high-FSC/low-SSC properties,
      whereas HO-Low cells formed a cluster of low-FSC/high-SSC cells. Analysis of the
      DNA extracted from cells sorted on the basis of scatter properties alone
      confirmed that the low-FSC/high-SSC population contained the apoptotic cells and
      that the high-FSC/low-SSC population was comprised of viable cells. This
      methodology allowed us to determine the percentage of apoptotic cells following
      anti-CD3 activation at various time points and to discriminate them from those in
      cell cycle. We could further quantitate the number of apoptotic versus viable
      CD4+ and CD8+ cells in the cell cycle.

PMID- 7507027
TI  - Incidence and distribution of opportunistic lung infections in AIDS patients
      related to intravenous drug use: a study of bronchoalveolar lavage cytology by
      the Diff-Quik stain.
AB  - The present study was undertaken in order to determine the incidence and
      distribution of opportunistic lung infections in patients with acquired
      immunodeficiency syndrome related to intravenous drug use. One hundred ninety
      seven patients of both sexes were investigated. Based on bronchoalveolar lavage
      cytology, a total of 156 (79%) patients were found to harbor opportunistic lung
      infections by the Diff-Quik staining procedure. Seventy-nine percent of the males
      and 80% of the females were positive. Pneumocystis carinii was the most common of
      the opportunistic infections accounting for 83% of the positive cases.
      Cryptococcus, Candida sp., and Aspergillus sp. were also identified in a small
      number of patients. Cytomegalovirus was not detected in any of the cases under
      study. There were no sex-related differences in the distribution of the various
      infectious agents, males and females being equally affected.

PMID- 7507025
TI  - Differences in relative DNA content between human peripheral blood and bone
      marrow subpopulations--consequences for DNA index calculations.
AB  - By sequentially staining for leukocyte differentiation antigens with monoclonal
      antibodies and for stainable DNA content with propidium iodide, we have evaluated
      the DNA ratios of normal peripheral blood and bone marrow subpopulations. In 19
      peripheral blood samples the relative DNA content of the monocytes was higher
      than that of other subpopulations, with highly significant differences between
      the DNA ratios of the CD14+ monocytes, on the one hand, unlabeled controls, CD3+
      T-lymphocytes, and CD20+ B-lymphocytes, on the other. In bone marrows from 16
      healthy volunteers, the relative DNA content of the myelomonocytic subpopulations
      was higher than that of the T-lymphocytes with significant differences between
      the CD3+ lymphocytes, on the one hand, and the CD14+ monocytes, the CD13+ and
      CD33+ immature myeloid, the NAT9+ mature myeloid, and the AS-E1+ nucleated
      erythroid subpopulation, on the other. Since a mixture of peripheral blood
      mononuclear cells or T lymphocytes from healthy volunteers is often used as an
      external standard for DNA ploidy determinations, these data suggest that such a
      procedure could result in an overestimation of the DNA indices of most of the
      bone marrow subpopulations. Instead, we suggest the use of the DNA ratio of the
      CD14+ subpopulation from peripheral blood as standards for ploidy determinations
      for the myeloid bone marrow subpopulations.

PMID- 7507026
TI  - Rapid separation of CD4+ and CD19+ lymphocyte populations from human peripheral
      blood by a magnetic activated cell sorter (MACS).
AB  - Rapid purification of human lymphocyte subpopulations is an essential step in
      order to elucidate their interactions and/or contributions in various disease
      states. Cell purification using a Magnetic Activated Cell Sorter (MACS) is a
      relatively new technology which has been shown to be rapid and yield highly
      purified populations of cells. This report describes both a simple one-step
      positive selection method using the MACS to purify either human CD4+ or CD19+
      lymphocytes from PBMC and a sequential separation of both CD4+ and CD19+ cell
      populations. These methods can separate the cell populations in approximately 4 h
      with yields > 90% and purity of 97 +/- 3% for CD4+ T cells and 92 +/- 5% for
      CD19+ B cells. In functional studies, purified CD19+ B cells secreted 13- and 24
      fold more IgM and IgG, respectively, than the CD19- cell fraction in 10 day B
      cell stimulation assays. Purification of the two cell types did not cause any
      significant activation as shown by proliferation. Both cell types, however, were
      able to proliferate upon stimulation with interleukin-2.

PMID- 7507028
TI  - [Palliative therapy of complex hilar biliary obstructions using self-expanding
      metal stents].
AB  - Implantation of self-expandable metal stents was planned for 21 patients (12
      women, 9 men; mean age 64.7 +/- 11.6 [38-80] years) with malignant obstructive
      jaundice due to complex hilar biliary obstruction (Bismuth II: n = 5, Bismuth
      III: n = 13, Bismuth IV: n = 1, state after hepaticojejunostomy: n = 2). Stents
      were implanted bilaterally in 18 patients (one each on the right and left, n =
      12; two stents on right, one stent on left, n = 6), one patient had three stents
      on one side, another had one unilateral stent. Thus there was a 93.3% success
      rate (46 of 49 planned stent implantations). The mean bilirubin level fell from
      14.7 +/- 7.7 mg/dl before stent implantation to 3.9 +/- 5.4 mg/dl afterwards (P =
      0.0001). One patient experienced late bleeding with haemorrhagic shock and
      consumption coagulopathy after a failed drainage attempt. She died despite
      superselective embolization, operative suturing of the puncture site, and wide
      ranging intensive care measures. Procedure-related death rate was thus 4.8%, the
      30-day death rate 9.5%. During the follow-up period, averaging 145 +/- 152 (16
      529) days, jaundice recurred in six patients (30%) and was successfully treated
      by re-intervention in five. 13 patients died after a mean survival time of 98 +/-
      119 (16-432) days. It is concluded from these data that self-expandable metal
      stents provide minimally invasive palliative treatment of complex biliary hilar
      obstruction in the type of case in which plastic stents are known to fail.

PMID- 7507029
TI  - Restricted expression of the hyaluronan receptor, CD44, during postimplantation
      mouse embryogenesis suggests key roles in tissue formation and patterning.
AB  - CD44 is a multifunctional adhesion protein that acts as a major receptor for the
      hygroscopic extracellular matrix component, hyaluronan. This receptor-ligand
      binding directly mediates at least some of the cell-cell and cell-matrix
      interactions ascribed to CD44. Other interactions involving CD44 may be modulated
      indirectly by its ability to bind growth factors and thereby to promote cell
      attachment. During vertebrate development, multiple cases of hyaluronan
      involvement in cell proliferation, cell migration and histogenesis have been
      documented. In addition, there is evidence suggesting a central role for cell
      surface glycoproteins and proteoglycans in mediating the action of polypeptide
      growth factors involved in tissue patterning. In view of this, we undertook to
      investigate expression of the CD44 protein during postimplantation mouse
      embryogenesis. Between 9.5 and 12.5 days of embryonic development, the
      predominant form of CD44 protein corresponds to the hyaluronan-binding CD44H
      form. However, species with a higher M(r) were also detected, implying that CD44
      isoforms generated by alternative splicing of CD44 RNA are employed in normal
      development. Further, we used mouse embryos to perform whole-mount
      immunohistochemistry and examine the temporal and spatial distribution of this
      glycoprotein. CD44 is expressed at high levels in the heart, somites and
      condensing limb-bud mesenchyme at critical stages of morphogenesis. These sites
      correlate with regions where hyaluronan has been demonstrated to regulate
      morphogenetic events. Of novel interest, however, is the high expression of CD44
      in regions that do not correlate with sites of known hyaluronan-mediated
      developmental events. These include instructive epithelia participating in
      epithelial-mesenchymal cell interactions such as the apical ectodermal ridge of
      the developing limb bud and the odontogenic placodes of the presumptive upper and
      lower jaws.

PMID- 7507030
TI  - Distribution of swallow protein in egg chambers and embryos of Drosophila
      melanogaster.
AB  - The Drosophila maternal effect gene swallow has a role in localizing bicoid mRNA
      at the anterior margin of the oocyte during oogenesis, and a poorly characterized
      role in nuclear divisions in early embryogenesis. We have examined the
      distribution of swallow protein during oogenesis and embryogenesis using anti
      swallow antibodies. During oogenesis, high levels of swallow protein are present
      in basal nurse cell cytoplasm, although small amounts are also present at the
      anterior oocyte margin, the site of bicoid RNA localization. Only a small
      fraction of swallow protein is in a position to interact directly with bicoid RNA
      during localization. The asymmetric distribution of swallow protein is disrupted
      in swallow ovaries, in which bicoid RNA becomes unlocalized late in oogenesis.
      swallow protein is uniformly distributed in eggs, but becomes localized to nuclei
      during early mitotic divisions in early embryogenesis. swallow protein enters
      each nucleus at the beginning of mitosis, occupies a position complementary to
      that of condensed chromatin, and leaves each nucleus at the end of mitosis. We
      show examples of nuclear division defects in swallow mutant embryos, and suggest
      that the abnormal nuclear divisions in early swallow embryos reflect a second
      function for swallow protein that contributes to abdominal segmentation defects
      common in swallow embryos.

PMID- 7507031
TI  - Endothelins. Vascular actions and clinical implications.

PMID- 7507032
TI  - Meta-analysis. A review of its place in therapeutic decision making.
AB  - The potential value of meta-analysis has captured the imagination of many
      investigators. Epidemiologists have, appropriately, greeted its broad application
      with considerable caution, yet practical matters, such as the need to consolidate
      and extract information from available data, have forced a more accepting
      approach. Meta-analysis has been employed in many clinical settings to evaluate
      efficacy and safety of a variety of therapeutic interventions. It is likely that
      it will continue to have a role in extrapolating data from clinical trials for
      use in the clinic.

PMID- 7507033
TI  - Tamoxifen as adjuvant therapy in breast cancer. Current status.
AB  - Tamoxifen retains its place as the most important drug in the management of human
      breast cancer. As time passes, it becomes clear that this drug is no longer to be
      regarded as a simple antiestrogen, since it modifies other cellular signalling
      mechanisms, giving scientific credence to the growth inhibitory effects observed
      in estrogen receptor-negative tumours. With the role of tamoxifen in breast
      cancer being well documented, recent interest has concentrated on its now proven
      efficacy in adjuvant treatment of patients with the disease in its early stages,
      and on its prophylactic role in women at high risk of developing the disease. For
      tamoxifen to have any role at all in the latter situation, it must be
      demonstrably safe, and here again the toxicity profile is now much better
      understood.

PMID- 7507034
TI  - Nonsteroidal anti-inflammatory drugs and chondroprotection. A review of the
      evidence.

PMID- 7507036
TI  - Drug treatment for hyperactive children. Therapeutic guidelines.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioural
      disorder and medication is one of the principal treatments. Methylphenidate and
      dexamphetamine (dextroamphetamine) have a long record of use in children and well
      proven efficacy, and are the preferred drugs. Current clinical guidelines
      recommend a trial of methylphenidate and of dexamphetamine for each child meeting
      criteria for the disorder in order to maximise response rate and minimise adverse
      effects.

PMID- 7507035
TI  - Clinical pharmacology of asthma. Implications for treatment.
AB  - The past 10 years have seen three important changes in the philosophy of managing
      asthma. First, histological studies using fibreoptic bronchoscopy have led to the
      recognition that asthma is an inflammatory condition of the bronchial mucosa and
      is not simply caused by smooth muscle spasm. Secondly, there has been some
      disenchantment with the long term use of regular beta 2-adrenergic agonists as
      these agents do not appear to control bronchial inflammation and have been
      associated with deaths from asthma. Thirdly, there has been a general shift away
      from physician-centred management towards patient-oriented management plans.
      These three separate strands have led to the development of regional and
      international consensus documents that emphasise the use of regular anti
      inflammatory treatment to control bronchial inflammation and reduce symptoms.
      With the emphasis on finding the minimum amount of treatment, several traditional
      anti-asthma medications have been downgraded in importance. The introduction of
      self-management plans is to be welcomed, but it is important that these new
      strategies for treating asthma are properly evaluated so that the benefits they
      confer can be ascertained and maximised.

PMID- 7507037
TI  - Cladribine. A review of its pharmacodynamic and pharmacokinetic properties and
      therapeutic potential in haematological malignancies.
AB  - Cladribine (2-chloro-2'-deoxyadenosine) is an adenosine deaminase-resistant
      analogue of deoxyadenosine. In the treatment of hairy cell leukaemia, cladribine
      has demonstrated excellent efficacy (complete response in 33 to 92% of patients)
      in noncomparative studies. Cladribine appears to compare favourably with other
      systemic agents in this indication as it achieves a high degree of efficacy after
      a single 7-day course, with an acceptable tolerability profile. However, long
      term data and direct comparative studies with interferon-alpha and pentostatin
      (deoxycoformycin) are required to confirm the finite advantages offered by
      cladribine. Preliminary results obtained in other indications including chronic
      lymphocytic leukaemia, non-Hodgkin's lymphoma, cutaneous T cell lymphoma,
      Waldenstrom's macroglobinaemia and acute myeloid leukaemia in children have been
      sufficiently encouraging to warrant further study. Early pharmacokinetic data
      suggest that cladribine may be administered by oral and subcutaneous routes, both
      of which permit convenient outpatient therapy. Myelosuppression, the dose
      limiting toxicity of cladribine, and culture-negative fever are the most common
      adverse effects associated with therapy. However, cladribine appears to be only
      rarely associated with many of the other adverse effects that characterise
      antineoplastic therapy. In the weeks post-treatment, there is a small but
      definite risk of serious infection; infections with a fatal outcome have been
      reported in a number of studies with cladribine. In conclusion, preliminary data
      concerning cladribine have been extremely encouraging. Should early response
      rates in patients with hairy cell leukaemia be sustained, the efficacy of the
      drug, together with a short treatment regimen, a favourable tolerability profile,
      and the possibility of oral therapy, suggest that cladribine is likely to
      supersede other agents available for this indication.

PMID- 7507039
TI  - Tropisetron. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic potential as an antiemetic.
AB  - Tropisetron is a potent and selective serotonin 3 (5-hydroxytryptamine3; 5-HT3)
      receptor antagonist with antiemetic properties, probably mediated via antagonism
      of receptors both at peripheral sites and in the central nervous system. When
      compared with antiemetic regimens containing high-dose metoclopramide in a small
      number of studies, tropisetron was generally as effective at preventing acute and
      delayed vomiting induced by high-dose cisplatin (> or = 50 mg/m2). In these
      studies tropisetron completely prevented vomiting occurring in the first 24 hours
      after chemotherapy in 35 to 76% of patients. Tropisetron was superior to
      alizapride in preventing emesis induced by high-dose alkylating agents. The
      effectiveness of tropisetron in patients who had previously had partial control
      of emesis was improved by the addition of dexamethasone. Tropisetron appears to
      be well tolerated with the most frequently reported adverse effect being
      headache. Extrapyramidal effects, which can occur in 5 to 10% of patients
      receiving high-dose metoclopramide and which may limit its use, have been
      reported in only isolated cases with tropisetron. Thus, tropisetron is an
      effective, apparently well tolerated agent which can be administered once daily
      for the prevention of chemotherapy-induced nausea and vomiting. However, further
      clinical experience is needed to clarify the optimum role of tropisetron as an
      antiemetic agent, particularly with regard to other drugs in its class.
      Nonetheless, preliminary results indicate that tropisetron will be a useful
      alternative for use in controlling emesis induced by cytotoxic therapy.

PMID- 7507041
TI  - Treatment of dysphagia and massive hemorrhage in esophageal carcinoma by ethanol
      injection.

PMID- 7507040
TI  - Albumin levels in pregnancy: a hypothesis--decreased levels of albumin are
      related to increased levels of alpha-fetoprotein.
AB  - Serum albumin levels decrease during pregnancy while the concentration of most
      other maternal serum proteins of hepatic origin remain stable or increase. In a
      study of 289 women, most maternal characteristics such as race, age, smoking, a
      history of previous low birth-weight, infant sex and gestational age at delivery
      were not related to maternal serum albumin levels at 18 or 30 weeks' gestational
      age. The degree of maternal obesity significantly correlated with the
      concentration of albumin. There was a significant negative correlation in
      individual women between maternal serum levels of albumin and alpha-fetoprotein,
      with high levels of maternal serum alpha-fetoprotein predicting lower levels of
      albumin. We hypothesize that there may be a negative feedback effect of alpha
      fetoprotein of fetal origin on the maternal production of albumin during
      pregnancy.

PMID- 7507038
TI  - Fluvoxamine. An updated review of its pharmacology, and therapeutic use in
      depressive illness.
AB  - Fluvoxamine facilitates serotoninergic neurotransmission via potent and selective
      inhibition of serotonin (5-hydroxytryptamine; 5-HT) reuptake into presynaptic
      neurones. The overall antidepressant efficacy of fluvoxamine 100 to 300 mg/day
      for 4 to 6 weeks in once daily or divided dosage regimens appears to be at least
      comparable to that of imipramine and similar to that of clomipramine, dothiepin,
      desipramine, amitriptyline, lofepramine, maprotiline, mianserin and moclobemide.
      The efficacy of fluvoxamine has been maintained for up to 1 year, but long term
      data are limited, and there are no comparative studies of fluvoxamine with other
      selective serotonin reuptake inhibitors. In some studies, fluvoxamine appeared to
      have an earlier beneficial effect on suicidal ideation and/or anxiety or somatic
      complaints compared with imipramine, dothiepin and maprotiline. Gastrointestinal
      adverse effects, especially nausea, are commonly reported with fluvoxamine but
      are generally mild to moderate in severity. The tolerability profile of
      fluvoxamine appears to be more favourable than that of tricyclic antidepressants
      in terms of cardiotoxic and anticholinergic adverse effects, sedation, weight
      gain and death from overdosage. Thus, fluvoxamine is an effective and well
      tolerated antidepressant agent that is becoming established as an alternative to
      older agents in patients with mild, moderate or severe depression. Fluvoxamine
      may be particularly beneficial in potentially suicidal patients with severe
      depression, in those with an underlying compulsive personality or cardiovascular
      disorder, in patients with coexistent anxiety or agitation, and in the elderly.

PMID- 7507042
TI  - Primary malignant melanoma of the esophagus palliated with endoscopic laser
      therapy.

PMID- 7507043
TI  - Characterization of the 48.5 kDa chorionic gonadotropin-like protein from
      Xanthomonas maltophilia.
AB  - Our laboratory has previously reported the isolation of a 48.5 kDa membrane
      protein from Xanthomonas maltophilia (ATCC 13637) which immunologically cross
      reacts with the beta-subunit of human chorionic gonadotropin (hCG) in both
      polyclonal and monoclonal radioimmunoassays (RIA) (1). The protein showed no
      reaction in RIAs for human LH, TSH, or the free alpha subunit of hCG. We have now
      improved the protein purification procedure and have obtained adequate bacterial
      protein to characterize the pure protein (designated xCG) in RIAs and also to
      obtain amino acid composition and partial sequence. We present these data and
      compare homology to hCG. An RIA for the bacterial protein has also been
      developed.

PMID- 7507044
TI  - Fluorodeoxyglucose cell incorporation as an index of cell proliferation:
      evaluation of accuracy in cell culture.
AB  - The use of fluorodeoxyglucose (FDG) and positron emission tomography (PET) is
      recognized as an accurate tool for the specific diagnosis and staging of cancer.
      It has also been proposed for the monitoring of anticancer therapy. FDG cell
      incorporation reflects glycolytic activity whereas inhibition of cell
      proliferation corresponds to an efficient cancer treatment. The relationship
      between FDG incorporation and cell proliferation has yet to be demonstrated.
      Therefore, we aimed to correlate the effects of the toxic agents bleomycin and
      unlabelled meta-iodobenzylguanidine (mIBG) on cellular metabolism and
      proliferation. We determined the in vitro metabolic and cytotoxic effects of
      bleomycin and mIBG by measuring the incorporation of fluorine-18 FDG (%UFDG) and
      hydrogen-3 thymidine (%UTHY) in cells of the human premonocytic line U937 in the
      presence of increasing concentrations of these agents. Proliferation rate of
      these cells was studied by means of limiting dilution analysis. %UTHY appeared
      more sensitive to bleomycin or mIBG-mediated cell injury than %UFDG. After 1 h of
      exposure to 0.5 microM bleomycin, %UTHY was significantly reduced to 62.0% +/-
      10.4% of control value whereas %UFDG remained unchanged (91.6% +/- 5.3%). Similar
      results were obtained after 1 h of exposure to increasing concentrations of mIBG
      (1 microM to 1 mM). After 20 h of exposure to bleomycin, %UTHY and %UFDG were
      significantly reduced as a function of concentration. After 20 h of exposure to
      mIBG, a transient increase in %UFDG up to 149.3% +/- 11.2% with 50 microM mIBG
      was further followed by a reduction to 20.1% +/- 6.7% with 0.5 mM (P <
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507047
TI  - Is transrectal ultrasonography needed to rule out prostatic cancer with normal
      findings at digital rectal examination and normal serum prostate-specific
      antigen?
AB  - In a prospective study, 288 consecutive patients without evidence for prostatic
      carcinoma at digital rectal examination (DRE) and scheduled for prostatectomy
      because of benign prostatic hyperplasia (BPH) were examined by transrectal
      ultrasonography (TRUS) and serum prostate-specific antigen (PSA) measurement
      prior to surgery. 46 patients were found to have a carcinoma at histological
      examination of the surgical specimens. 14 carcinomas were detected preoperatively
      by TRUS and biopsy (10 pT1, 3 pT2, 1 pT3) of 32 patients with suspicious, i.e.,
      hypoechoic, lesions at TRUS. Among the remaining 256 patients with normal
      findings at TRUS, another 32 carcinomas were found at histological examination of
      the surgical specimen. Of the 14 carcinomas detected by TRUS, 13 were found
      within a group of 57 patients with PSA levels > 7 ng/ml corresponding to a cancer
      detection rate of 22.8% in this group. In 231 patients with PSA < 7 ng/ml, the
      use of TRUS was successful in detecting only 1 carcinoma (cancer detection rate
      0.4%). These results suggest that the use of TRUS is dispensible in 80% of
      palpably normal patients without affecting the cancer detection rate.

PMID- 7507045
TI  - Neoadjuvant hormonal deprivation before radical prostatectomy.
AB  - Hormonal deprivation before radical prostatectomy remains controversial. The main
      purpose is to achieve downstaging, downgrading, improvement of the surgical
      results and increased survival. Experience with the last 100 patients who
      underwent radical prostatectomy, in whom 40 patients received complete
      preoperative androgen blockade (luteinizing-hormone-releasing hormone agonist and
      flutamide) prior to radical surgery, has shown a definitive decrease in volume of
      40-50%). The significant reduction of volume seemed to facilitate the dissection
      of the prostate from closely vulnerable structures. Clinical downstaging was
      observed in one third of the patients, but the final pathological staging did not
      confirm the clinical impression and shows that it is difficult to solve this
      issue. There was one PT0 patient. Histological changes are observed in both the
      nonneoplastic tissue as well as in the prostatic carcinoma with more marked
      effects on the latter. Downgrading was not observed, but this is even more
      difficult to assess since biopsies cannot be considered as representative of the
      entire heterogeneous tumor. Prostate-specific antigen (PSA) dropped to
      undetectable levels in 59% of the patients 3 months after hormonal suppression.
      Among these, 80% had PT2 and only 13% had PT3 tumor. PSA, 3 months after
      neoadjuvant hormonal treatment, might have a useful predictive value in patient
      selection for radical surgery since 86% with undetectable PSA had tumors confined
      to the gland (PT2/B2). On the other hand, patients who still had PSA > 4 ng/ml
      after neoadjuvant therapy had all stage PT3-PT4 disease.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7507046
TI  - Neoadjuvant GnRH-agonist treatment (triptorelin and cyproterone acetate for flare
      protection) and total prostatectomy.
AB  - The effects of 3 months treatment with the GnRH agonist triptorelin as a
      neoadjuvant to total prostatectomy in 40 men with localized prostatic cancer have
      been evaluated. The study included 1 patient with a stage T1b tumour, 25 patients
      with stage T2 tumours and 14 with stage T3 tumours. The patients were examined by
      digital rectal examination, transrectal ultrasound before and after treatment.
      Serum testosterone and prostate-specific antigen (PSA) levels were followed. The
      totally removed prostate gland was step-sectioned at 5-mm intervals and the whole
      mount sections were assessed for tumour pathology stage (pT stage). Triptorelin
      treatment resulted in a significant decrease in total gland and tumour volume and
      in a reduction in the serum levels of PSA and testosterone. In comparison with
      the findings from a previous study, in which neoadjuvant treatment was not used,
      it appears that the proportion of tumours invading the margins of the surgical
      specimen decreased.

PMID- 7507049
TI  - Finasteride, MSD: Innovation in the Management of Benign Prostatic Hyperplasia.
      Proceedings of a symposium. Seville, Spain, November 3, 1991.

PMID- 7507048
TI  - Clinical evaluation of a new prostate-specific antigen sandwich ELISA which
      employs four monoclonal antibodies directed at different epitopes of prostate
      specific antigen.
AB  - A known radioimmunometric prostate-specific antigen (PSA) test based on
      monoclonal antibodies, as well as a new PSA-ELISA utilizing 4 monoclonal
      antibodies directed against different epitopes of PSA were compared in a clinical
      evaluation. For the investigation, collectives of patient sera from patients with
      independently diagnosed prostatic carcinoma (PCA) as well as benign prostatic
      hyperplasia (BPH) were employed. The results of the evaluation demonstrated that
      although the PSA immunoradiometric test and the PSA-ELISA yielded different
      numerical values for PSA serum concentrations, they possess comparable diagnostic
      sensitivities as well as specificities. The nonradioactive PSA-ELISA could
      therefore substitute the PSA-IRMA in a clinical routine diagnostic of PCA.

PMID- 7507050
TI  - The natural history of benign prostatic hyperplasia: implications for patient
      care and clinical trial design.
AB  - Benign prostatic hyperplasia (BPH) is a nearly universal concomitant of male
      aging, yet its natural history is largely undocumented. Most information on the
      clinical course of untreated prostatism has come from a limited number of
      studies. This lack of information makes it difficult for urologists to know when,
      how, and in whom to intervene. This is reflected by the controversy surrounding
      surgical indications and by the considerable variability in rates of
      prostatectomy. Over the last 2 years, information on the natural history of BPH
      has been obtained from analyses of limited data from long-term, general-purpose,
      government-sponsored prospective studies of human aging. This paper briefly
      reviews these studies and discusses implications for patient care decisions and
      clinical trial design.

PMID- 7507051
TI  - Review of current treatment of benign prostatic hyperplasia.
AB  - The treatment of benign prostatic hyperplasia is changing, with many new
      modalities being tested: Some are already used routinely, others are still
      investigational. Surgery, however, is still the principal treatment, producing an
      85-90% improvement in symptoms and urodynamics. Stents are being used more
      frequently, particularly in patients with a high operative risk. Balloon dilation
      can be performed in small glands; however, the durability of results remains in
      doubt. Thermotherapy has been found to produce histologic changes in the prostate
      and may change the urodynamics as well. Finally, drug treatment, which is
      currently limited to a-blocking agents and 5 a-reductase inhibitors, has proven
      to be effective symptomatically, with small, but significant changes in
      urodynamics.

PMID- 7507053
TI  - Future implications for the management of benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a growing medical problem in terms of
      morbidity, mortality, and health care costs. Renewed research has highlighted the
      lack of standardized parameters available with which to define and evaluate BPH
      and its treatment. The many treatments available, ranging from surgery to
      watchful waiting, point to the complex pathophysiology of BPH and the
      subjectivity of the treatment decisions. Workup of patients with micturition
      disorders, coupled with use of the International Prostate Symptom Score
      evaluation, permits the development of criteria for evaluating treatment efficacy
      and acceptable treatment options. Based on double-blind, placebo-controlled
      trials, a-blockers and finasteride have been accepted as treatment options. The
      former produce relaxation of the smooth muscle by inhibiting adrenergically
      induced increases in intracellular calcium. The latter blocks the 5a-reductase
      system, which effectively stops the conversion of testosterone to
      dihydrotestosterone. a-Blockers improve symptoms and flow immediately while
      finasteride diminishes the prostate volume, specifically of glandular tissue,
      leading to improved symptoms and flow. All other medical and nonmedical
      treatments require further evaluation by randomized, prospective trials to
      determine their safety profile and efficacy.

PMID- 7507052
TI  - Finasteride for the treatment and control of benign prostatic hyperplasia:
      summary of phase III controlled studies. The Finasteride Study Group.
AB  - The efficacy and safety profiles of finasteride were tested in 1,645 patients
      with benign prostatic hyperplasia (BPH) over a 12-month period. The following
      effects were observed: (1) a 60-80% reduction in serum dihydrotestosterone
      levels; (2) a 20% reduction in prostate volume; (3) significant increases in the
      maximum urinary flow rate compared with placebo; and (4) significant improvement
      in urinary symptoms, particularly obstructive symptoms. All effects were well
      maintained for the entire duration of the study. Finasteride had a good safety
      profile and was well tolerated.

PMID- 7507054
TI  - Pathophysiology of benign prostatic hyperplasia.
AB  - The exact morphogenesis of benign prostatic hyperplasia (BPH) is unknown, but
      morphologic observations and different etiologic theories, such as the stem cell,
      dihydrotestosterone, and stromal-epithelial interaction hypotheses, help to
      explain some of the findings. For example, the initial changes in the development
      of BPH may result from an activation of mesenchymal clones with embryonal
      functions that stimulate development of the glandular component. This, in turn,
      induces the development and maturation of the stromal component. In areas that
      lack epithelial elements, such as those in the periurethral zone, the interaction
      stops and only embryonal small stromal nodules remain. On the other hand, the
      decrease in endocrine-paracrine cells may alter the normal local hormonal
      equilibrium of the periurethral area and may be an inducing factor in the
      development of BPH.

PMID- 7507055
TI  - Etiology of benign prostatic hyperplasia.
AB  - The natural history of benign prostatic hyperplasia (BPH) involves two phases.
      The first, or pathologic phase, is composed of two stages, microscopic and
      macroscopic, neither of which produces symptomatic clinical dysuria. Nearly all
      men throughout the world eventually develop microscopic BPH if they live long
      enough. In only about 50% of men, however, does microscopic BPH grow to produce a
      macroscopic enlargement of the gland, suggesting that additional factors are
      required for BPH progression. The second, or clinical, phase of BPH involves the
      progression of pathologic BPH to its clinical form, in which the patient develops
      symptomatic dysuria. Again, only about one half of the men with macroscopic BPH
      progress to clinical BPH. Although macroscopic enlargement of the prostate is
      necessary for the development of clinical BPH, it is usually not sufficient by
      itself for the progression to clinical BPH. Additional factors are required
      (e.g., prostatitis, vascular infarct, tensile strength of the glandular capsule).
      Successful treatment does not, therefore, require the prevention of pathologic
      BPH; instead, what is needed is a therapy to prevent or reverse the progression
      to clinical disease.

PMID- 7507057
TI  - Isbufylline, a new xanthine derivative, inhibits airway hyperresponsiveness and
      airway inflammation in guinea pigs.
AB  - The pharmacological actions of the new xanthine, isbufylline, were evaluated in
      several models of airway hyperresponsiveness and airway inflammation in guinea
      pigs. At a dose (106 mumol kg-1 i.p.) providing complete protection against
      acetylcholine aerosol-induced dyspnea in the guinea pig, isbufylline inhibited
      platelet activating factor (PAF)- and antigen-induced eosinophil infiltration
      into bronchoalveolar lavage fluid 24 h after challenge of normal and actively
      immunized guinea pigs, respectively. In addition, this dose of isbufylline also
      inhibited capsaicin-induced extravasation of protein into bronchoalveolar lavage
      fluid. Isbufylline, 4.2 mumol kg-1 i.v., significantly inhibited PAF-induced
      bronchial hyper-responsiveness to i.v. histamine, without exerting evident
      bronchodilator activity. On the other hand the bronchodilator, salbutamol, at a
      dose (10.4 mumol kg-1 i.p.) shown to be equieffective to isbufylline (106 mumol
      kg-1 i.p.) for blocking acetylcholine aerosol-induced dyspnea, had no protective
      action against PAF- or antigen-induced eosinophil recruitment in bronchoalveolar
      lavage fluid, or against capsaicin-induced plasma protein extravasation.
      Furthermore, salbutamol (3.5 mumol kg-1) significantly potentiated allergen
      induced cell infiltration and PAF-induced bronchial hyperresponsiveness. The
      results suggest that isbufylline can exert significant anti-inflammatory actions
      in guinea pig airways, in addition to its bronchodilator activity. These
      pharmacological activities are not shared by the beta 2-adrenoceptor agonist,
      salbutamol.

PMID- 7507056
TI  - Intrathecal 5-methoxy-N,N-dimethyltryptamine in mice modulates 5-HT1 and 5-HT3
      receptors.
AB  - The antinociceptive effects of intrathecally administered 5-methoxy-N,N
      dimethyltryptamine (5-MeO-DMT), a potent 5-HT receptor agonist, were studied in
      three behavioral tests in mice: the tail-flick test and the intrathecal substance
      P and N-methyl-D-aspartic acid (NMDA) assays. Intrathecal administration of 5-MeO
      DMT (4.6-92 nmol/mouse) produced a significant prolongation of the tail-flick
      latency. This action was blocked by 5-HT3 and gamma-aminobutyric acidA (GABAA)
      receptor antagonists but not by 5-HT2, 5-HT1A, 5-HT1B or 5-HT1S receptor
      antagonists. Binding studies indicated that 5-MeO-DMT had very low affinity for 5
      HT3 receptors. 5-MeO-DMT inhibited biting behavior while increasing scratching
      behavior induced by intrathecally administered substance P. The inhibition of
      biting behavior was antagonized by intrathecal co-administration of 5-HT1B and
      GABAA receptor antagonists while 5-HT1A, 5-HT1S, 5-HT2 and 5-HT3 receptor
      antagonists had no effect. 5-MeO-DMT-enhanced scratching behavior was inhibited
      by all the antagonists used except ketanserin and bicuculline, suggesting the
      involvement of 5-HT1A, 5-HT1B, 5-HT1S, 5-HT3 and GABAA receptors. NMDA-induced
      biting behavior was inhibited by 5-MeO-DMT pretreatment; this action was
      antagonized by 5-HT1B, 5-HT3 and GABAA receptor antagonists. The involvement of
      these receptors in 5-MeO-DMT action suggests that it may promote release of 5-HT
      (5-hydroxytryptamine, serotonin).

PMID- 7507058
TI  - Stimulation of the chemotactic migration of human fibroblasts by substance P.
AB  - Neuropeptides exert a variety of modulatory effects on inflammatory cellular
      responses. In order to investigate further activities of these cytokines on
      mechanisms in inflammatory processes, we determined the ability of substance P to
      promote human fibroblast chemotaxis. Cell migration was measured by two different
      assay types in modified Boyden chambers. Substance P was found to be a potent
      chemoattractant for human fibroblasts in vitro, eliciting a concentration
      dependent migratory response. In further investigations we tested the
      chemoattractant potency of the fragments substance P-(1-4) and substance P-(3
      11). As only the C-terminal analog promoted migratory responses, we suggest that
      the chemotactic responsiveness is largely encoded by the C-terminus of the
      neuropeptide, which is known to be active on neurokinin receptors. Involvement of
      neurokinin receptors of type 1 in the chemotactic response to substance P was
      indicated by fibroblast migration toward optimal concentration of a selective NK1
      receptor agonist but not a NK2 receptor agonist. The observed ability of human
      fibroblasts to respond chemotactically to substance P elucidated another
      proinflammatory activity of this neuropeptide.

PMID- 7507059
TI  - Brain vessels near muscle autografts are sites for entry of isogeneic macrophages
      into brain.
AB  - An autograft of skeletal muscle on rat dorsal medulla is a permanent opening in
      the blood-brain barrier to solutes. Is the graft also a site for the entry of
      exogenous, isogeneic leukocytes? Five weeks after inserting the graft, peritoneal
      macrophages (M phi) from inbred Fischer rats were activated by phorbol myristate
      acetate, labeled with a fluorescent dye, and infused as a bolus of about 2 x
      10(6) cells into the axillary artery of Fischer hosts. The cells circulated for 2
      h. The brains were then fixed, frozen, and sectioned. Only when M phi had been
      activated and a muscle autograft inserted did appreciable numbers of M phi enter
      the medulla. Nonactivated M phi invaded the grafts but very few entered the brain
      at 2 h. In rats with gel foam grafts, only a few activated M phi invaded gel and
      brain. Before entering tissues, M phi must adhere to the lumenal face of vessels.
      Cell adhesion molecules, e.g., I-CAM-1 and its ligand adhesion molecule,
      leukocyte function antigen (LFA-1), are known to mediate adhesion. I-CAM-1,
      detected immunohistochemically, increased in graft vessels and in nearby brain
      vessels. The rise may have been mediated by cytokines, interleukin-6, and tumor
      necrosis factor-beta, found in the grafts. LFA-1, however, assayed by
      fluorescence-activated cell sorting, was on both activated and nonactivated,
      exogenous M phi. Thus, M phi-endothelial attachment may have involved other
      adhesion molecules, e.g., selectins. The autograft also induced major
      histocompatibility complex class I on microglia and classes I and II on brain
      vessels near the graft. These vessels, by expressing adhesion molecules, are
      entry routes into brain for activated, isogeneic leukocytes that can then migrate
      for a limited distance of 1-2 mm in an otherwise intact brain.

PMID- 7507060
TI  - Differential effects of suicide transport lesions of the striatonigral or
      striatopallidal pathways on subsets of striatal neurons.
AB  - In the basal ganglia, centrally active suicide transport agents produce
      apparently selective lesions of the striatopallidal and striatonigral pathways
      based on receptor binding and neuropeptide mRNA studies. In the present study we
      sought to determine the selectivity of suicide transport lesions for specific
      subsets of striatal neurons. Using immunohistochemical methods, the neostriata of
      adult rats were examined 10 days after an injection of volkensin into the
      substantia nigra or an injection of OX7-saporin into the globus pallidus. Ricin,
      a suicide transport agent active in the peripheral but not the central nervous
      system, was injected into each target as a control. Adjacent sections were
      processed for (1) Nissl stain to assess neuronal density, both overall and for
      large interneurons, (2) NADPH-diaphorase (NADPH-d) histochemistry, to mark medium
      sized aspiny interneurons, (3) enkephalin immunocytochemistry, to label
      striatopallidal neurons, or (4) substance P immunocytochemistry, to label
      striatonigral neurons. Ricin injections produced no change in the densities of
      these subsets of striatal cells. In animals receiving volkensin or OX7-saporin
      injections, analyses of Nissl material revealed that the striata ipsilateral to
      the toxin injections appeared normal and did not exhibit shrinkage or gliosis;
      however, a quantitation analysis revealed a moderate decrease in cell density (12
      16% loss, P < 0.01). The densities of both large and NADPH-d-containing striatal
      interneurons were unchanged after lesions in either target. Following nigral
      injections with volkensin, the density of striatal substance P-labeled cells
      decreased (26% loss, P < 0.01), while the density of enkephalin-labeled cells did
      not decrease significantly (11% decrease, P > 0.1). After pallidal injections
      with OX7-saporin, the density of striatal enkephalin-labeled cells decreased (20%
      loss, P < 0.01), while that of substance P-labeled cells remained unchanged.
      These data show that nigral volkensin and pallidal OX7-saporin injections
      differentially lesion striatonigral and striatopallidal projection neurons and
      spare striatal interneurons. This study provides further evidence for the
      selectivity, specificity, and utility of suicide transport agents to study brain
      structure and function.

PMID- 7507061
TI  - On the guidance of regenerating axons from a half-retina in the adult goldfish.
AB  - We have examined the guidance of regenerating optic axons from half-retinal
      fragments in the goldfish. Axons regenerating from a dorsal, ventral, or nasal
      half-retina showed no bias to grow through the retinotopically appropriate parts
      of the optic tract. By contrast, axons from a temporal half-retina did show a
      bias, albeit a small one, to grow through the correct part of the tract. In
      addition, we found evidence that axons from the temporal quadrant of dorsal or
      ventral half-retinas showed a similar bias. In the optic tectum, axons
      regenerating from a dorsal, ventral, or temporal half-retina showed strong biases
      to invade the retinotopically appropriate portion of the synaptic field. Of these
      three, temporal axons showed the sharpest restriction in their field of
      innervation. Nasal fibers were unique in that they invaded the entire tectum with
      little evidence of a preference for their appropriate field. Our results indicate
      that there is minimal guidance offered to regenerating optic axons in the optic
      tract. However, once dorsal, ventral, or temporal axons reach the tectum they
      appear to encounter strong organizing forces which constrain them to
      preferentially invade their retinotopically appropriate areas. Nasal axons appear
      to be exempt from these forces. In both the optic tract and tectum, axons from a
      temporal half-retina are the most effectively guided and constrained.

PMID- 7507062
TI  - Consequences of reduced cerebral blood flow in brain development. I. Gross
      morphology, histology, and callosal connectivity.
AB  - Reduced blood flow produced by bilateral carotid artery occlusion (BCAO) caused
      multiple histopathological alterations in the cerebral cortex of developing cats.
      BCAO was performed in the second postnatal week. At 1 and 2 months, global
      structural observations were made using magnetic resonance imaging (MRI). At 3
      months, neuron and glial density, extent of myelination, blood vessel
      distribution, and the distribution of visual callosal projecting neurons (as
      visualized with the retrogradely transported tracer horseradish peroxidase) were
      assessed by light microscopy. MRI showed lateral ventricular dilatation at 1
      month in five of eight subjects, with wide-ranging severity, although at 2 months
      only two animals still had enlarged ventricles. Histological observations at 3
      months showed that neuron density in the motor cortex, but not the occipital
      cortex, of BACO animals was significantly lower than that in controls. BCAO
      animals had more dilated small vessels, again more evident in the motor cortex
      than in the occipital cortex. From frontal to occipital cortex, the corpus
      callosum was thinned and the subcortical white matter was reduced. Even with the
      reduction of white matter, the number of neurons in visual areas 17 and 18
      contributing a callosal projection was much higher than normal. BCAO thus altered
      cerebral vascularization, caused neuronal death, and reduced myelinization over
      an area much greater than the direct area of carotid perfusion. The excess
      callosal projection in these animals suggests that neonatal ischemia interferes
      with the normal process of axon retraction during development.

PMID- 7507063
TI  - Insulin induces tyrosine phosphorylation of a 90-kDa protein during postischemic
      brain reperfusion.
AB  - Rat brain nuclear proteins were examined for tyrosine phosphorylation after
      resuscitation from a 10-min cardiac arrest. Insulin (1 unit/kg intravenously),
      given immediately after resuscitation, caused a marked increase in tyrosine
      phosphorylation of a 90-kDa brain protein. This effect occurred without
      hypoglycemia and was not observed after insulin administration in previously
      insulinopenic, diabetic, nonischemic animals. Insulin-responsive tyrosine
      phosphorylation of a specific 90-kDa protein during reperfusion may represent
      insulin stimulation of a neuroprotective brain response to an ischemic insult,
      consistent with recent observations that insulin administration during
      reperfusion protects selectively vulnerable neurons from postischemic death.

PMID- 7507064
TI  - Retarded development of neurons and oligodendroglia in rat forebrain produced by
      hyperphenylalaninemia results in permanent deficits in myelin despite long
      recovery periods.
AB  - The severe hypomyelination seen in the CNS of untreated phenylketonuria (PKU)
      patients has been suggested to be the result of a defect in the process of
      myelination itself. Using chronic hyperphenylalaninemia (HPA) in rats as a model
      of PKU we have previously shown, by immunohistochemistry, that axonal maturation
      as well as myelination was severely retarded. In the present study we have used
      image analysis techniques to quantitate changes in myelin basic protein (MBP) and
      200-kDa neurofilament protein (NF-H) immunostaining in the corpus callosum and
      cerebral cortical grey matter of HPA rats. No difference in the density of MBP+
      myelin was observed in the corpus callosum after 24 days HPA treatment although
      the width of the tract was much reduced. In contrast there was a deficit in NF-H
      immunostaining. Large deficits in both myelin and axonal maturity were seen in
      the cortical grey matter. Following a 6-week recovery period, despite recovery in
      the corpus callosum, large deficits in both MBP and NF-H were still seen in all
      cortical layers. Deficits in NF-H immunostaining were two to three times greater
      than those for MBP. On increasing the recovery period to 18 weeks significant
      deficits in myelin remained in layers I-III of the cortical grey matter whereas
      NF-H immunostaining had returned to normal levels in all layers. Our data suggest
      a primary effect of HPA on neuronal development, in particular axonal maturation,
      with a secondary hypomyelination and show that permanent deficits in myelinated
      axons in outer cortical layers can result when myelination is severely inhibited
      during a critical developmental period.

PMID- 7507065
TI  - Increased amount of nitric oxide in exhaled air of asthmatics.
AB  - The presence of nitric oxide (NO) in the exhaled air of humans has recently been
      described. We wanted to assess at what level exhaled NO originates in normal
      airways, and to determine whether airway inflammation induces changes in the
      levels of exhaled NO. Exhaled NO was continuously measured by chemiluminescence
      technique during normal tidal breathing through the nose or mouth, with a
      detection limit of 1 part per billion (ppb). Twelve control subjects were
      compared to eight patients with mild atopic asthma and rhinitis caused by
      occupational allergen. In control subjects, the major part of NO in exhaled air
      (up to 30 ppb) seemed to originate in the nasal airways, with only minor
      contribution from the lower airways and the oral cavity. However, in mild
      asthmatics, the level of exhaled NO during oral breathing, indicating the
      involvement of the lower airways, was increased 2-3 fold. Since increased
      production of NO in the lower airways may involve activated macrophages or
      neutrophils, we suggest that exhaled NO may be used to instantly monitor ongoing
      bronchial inflammation, at least when involving inducible NO synthase.

PMID- 7507066
TI  - Isoforms of cellular fibronectin and tenascin in amniotic fluid.
AB  - Amniotic fluid (AF) obtained from second trimester pregnancies presented
      extradomain (ED) A, B and an oncofetal (onc-f) domain containing isoforms of
      cellular fibronectin (cFn) in Western blotting of gelatin-bound polypeptides and
      directly of AF. Western blotting after sequential immunoprecipitation suggested
      at least three Fn molecules: one containing EDA and the onc-f domain and another
      minor component distinctly containing all the domains, and a third one only
      containing EDA. The immunoblotting results for EDA-cFn and onc-f-cFn were closely
      similar to that for total Fn, whereas in plasma samples of normal and pregnant
      women only traces of EDA-cFn and onc-f-cFn, but no EDB-cFn, were found. Western
      blotting of AF also indicated the presence of three isoforms of tenascin (Tn),
      M(r) 190,000 and 280,000 polypeptides earlier found in many cells, and a M(r)
      200,000 polypeptide, novel for AF and not present in plasma. The results suggest
      a novel extracellular matrix polypeptide composition for AF.

PMID- 7507067
TI  - The kinetics of conformational changes of alpha 2-macroglobulin determined by
      time resolved X-ray solution scattering.
AB  - The rate of gross conformational change of alpha 2-macroglobulin (alpha 2M)
      during its proteinase trapping was directly determined for the first time using
      time-resolved X-ray solution scattering. Decrease of radius of gyration was
      observed under pseudo-first-order conditions with excess proteinases, which
      exhibited a monophasic time-course. The rate constants were 0.5 +/- 0.1 s-1 and
      0.8 +/- 0.2 s-1 for the reaction with chymotrypsin and trypsin, respectively.
      There was no concentration dependence of the observed rate constants. Therefore,
      the rate-limiting step of the gross conformational change was not the bimolecular
      encounter reaction between alpha 2M and proteinases, which requires a new
      proposal of pre-trapping of proteinases before the gross conformational change.

PMID- 7507068
TI  - Regulation of insulin-like growth factor-binding protein-1 in rat serum.
AB  - Previous studies support a role for insulin-like growth factor-binding protein-1
      (IGFBP-1) in modulating insulin-like growth factor (IGF) availability for glucose
      homeostasis. We have developed a radioimmunoassay (RIA) for rat IGFBP-1 (rIGFBP
      1) and have examined the regulation of circulating levels by nutritional and
      hormonal status. Rabbit antisera were raised against pure rIGFBP-1, and an assay
      was established with a sensitivity of 50 pg. In the rat, serum IGFBP-1
      concentrations decrease with increasing developmental age. They were highest in
      fetal rat serum, exceeding 4 mg/L, and decreased to < 0.1 mg/L in adult animals.
      Serum rIGFBP-1 levels increased during fasting, 6-fold after 24 h and 18-fold
      after 48 h, and were suppressed to levels identical to ad libitum-fed control
      rats within 2 h of refeeding. Fasting levels were > 2-fold higher in female than
      male animals. IGFBP-1 concentrations were suppressed by > 50% in two rat models
      of insulin resistance. Levels increased in STZ-induced (streptozotocin) diabetes
      and were suppressed to normal with insulin treatment. Exercise stimulated rIGFBP
      1 concentrations in fasting animals. On immunoblotting after SDS-PAGE (sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis), rIGFBP-1 in serum appeared
      as a doublet with molecular masses at 31 and 33 kD. The components of this
      doublet did not vary across the range of experimental conditions. These
      observations indicate that the pattern of regulation of rIGFBP-1 is similar to
      that seen in previous studies of human IGFBP-1, with age, sex, and nutritional
      status being important regulators.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507069
TI  - [Palliative treatment by endoprosthesis of icterus caused by distal biliary
      tumoral obstruction].
AB  - Between March 1982 and December 1987, 466 patients (256 women, 210 men, mean age
      73 years) with tumor obstruction of the common bile duct were referred to our
      department. The causes of obstruction were carcinoma of the pancreas (298
      patients), carcinoma of the ampulla of Vater (32 patients) and carcinoma of the
      common bile duct (136 patients). Endoscopical insertion of a biliary prosthesis
      was initially possible in 377 patients (81%). In case of failure, patients were
      referred to the radiologist for percutaneous drainage. Successful drainage was
      obtained in 58 patients with an overall success rate of 93% (435 patients).
      Endoscopic replacement was necessary in 170 cases for 114 patients and was
      successful in 155 (91%). Pruritus was relieved in 89% of the patients. Serum
      bilirubin levels decreased more than 75% after initial endoscopic endoprosthesis,
      repeated endoscopic endoprosthesis and percutaneous prosthesis insertion in 80%,
      79%, and 62% of the patients, respectively. Short term complications of
      endoscopic endoprosthesis occurred in 28% of patients with a mortality rate of
      8%. Percutaneous prosthesis complications occurred in 33% of patients with a
      mortality rate of 11%. In the long term, cholangitis was the main complication
      and occurred in 27% of patients with a delay of 103 +/- 105 days. Intestinal
      obstruction was observed in 7% of patients. The average life expectancy of
      endoscopic endoprosthesis and percutaneous prosthesis was 109 +/- 157 and 92 +/-
      101 days, respectively. The average life expectancy of patients was 163 +/- 224
      days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507071
TI  - [Palliative endoscopic treatment of malignant biliary stenoses with self
      expanding metal endoprosthesis].

PMID- 7507070
TI  - [Palliative endoscopic treatment of malignant stenoses of the esophagus and
      cardia].

PMID- 7507072
TI  - [Palliative endoscopic treatment of cancer of the esophagus].

PMID- 7507073
TI  - Heterogeneity of histamine releasing factors and IgE.
AB  - Advances in our understanding of cytokines and their effects seem to occur almost
      on a daily basis. The first description of a cytokine causing histamine release
      was in 1979. Since that time several cellular products have been described which
      cause histamine release. The following is a general review of the literature
      concerning histamine releasing factors and their IgE interactions.

PMID- 7507074
TI  - Activation of the c-Src tyrosine kinase is required for the induction of mammary
      tumors in transgenic mice.
AB  - Transgenic mice expressing the polyomavirus (PyV) middle T oncogene in the
      mammary epithelium develop multifocal mammary tumors that metastasize with high
      frequency. The potent transforming activity of PyV middle T antigen can, in part,
      be attributed to its ability to associate with and to activate a number of c-Src
      family tyrosine kinases (c-Src, c-Yes, and Fyn). As a first step toward assessing
      the role of individual c-Src family tyrosine kinases in PyV middle T antigen
      induced mammary tumorigenesis, we have crossed transgenic mice carrying the mouse
      mammary tumor virus (MMTV)/PyV middle T antigen fusion gene with mice bearing a
      disrupted c-src proto-oncogene. In contrast to the rapid tumor progression seen
      in the original MMTV/PyV middle T antigen strains, mice expressing the transgene
      in the absence of functional c-Src rarely developed mammary tumors. After long
      latency, these mice did eventually develop abnormal hyperplastic mammary tissue.
      This growth disturbance was correlated with elevated expression of the PyV middle
      T antigen and the activation of the PyV middle T antigen-associated c-Yes
      tyrosine kinase. However, transgenic mice expressing the PyV middle T antigen in
      the mammary epithelium of wild-type or Yes-deficient mice developed multifocal
      mammary tumors with comparable kinetics. Taken together, these findings suggest
      that c-Src tyrosine kinase activity is required for PyV middle T antigen-induced
      mammary tumorigenesis and also illustrate an in vivo genetic approach to the
      dissection of mitogenic signal transduction pathways.

PMID- 7507075
TI  - Long-range restriction map of human chromosome 22q11-22q12 between the lambda
      immunoglobulin locus and the Ewing sarcoma breakpoint.
AB  - A long-range restriction map of the region between the immunoglobulin lambda
      locus and the Ewing sarcoma breakpoint has been constructed using the rare
      cutting enzymes NotI, NruI, AscI, and BsiWI. The map spans approximately 11,000
      kb and represents about one-fifth of the long arm of chromosome 22. Thirty-nine
      markers, including seven NotI junction clones as well as numerous genes and
      anonymous sequences, were mapped to the region with a somatic cell hybrid panel.
      These probes were then used to produce the map. The seven NotI junction clones
      each identified a possible CpG island. The breakpoints of the RAJ5 hybrid and the
      Ewing sarcoma t(11;22) were also localized in the resulting map. This physical
      map will be useful in studying chromosomal rearrangements in the region, as well
      as providing the details to examine the fidelity of the YAC and cosmid contigs
      currently under construction. Comparisons of this physical map to genetic and
      radiation hybrid maps are discussed.

PMID- 7507076
TI  - Structure of the murine VCAM1 gene.
AB  - The architecture of the murine VCAM1 gene, encoding vascular cell adhesion
      molecule-1, was determined. its 10 exons span approximately 20 kb. Exon 1 encodes
      the 5' untranslated region and the signal peptide; exons 2-4 and 6-9, the C2 or H
      type immunoglobulin domains; and exon 10, the transmembrane and cytoplasmic
      domains followed by the entire 3' untranslated region. All immunoglobulin-like
      domains are encoded by separate exons, and exon splice junctions occur after the
      first nucleotide of amino acid codons (type 1). Exon 5 encodes a novel domain
      unique to murine VCAM-1 and inclusion of this exon by alternative splicing
      results in a truncated three-immunoglobulin-like domain form, which is bound to
      the cell membrane by a phosphatidylinositol linkage at its carboxy terminus
      (encoded by exon 5). The murine VCAM1 core promoter contains a high degree of
      homology to the human, including conserved consensus binding sites for NF-kappa
      B, the Ets class, and the GATA family of transcription factors, suggesting that
      the murine and human VCAM1 genes may be under similar transcriptional control.

PMID- 7507077
TI  - Sequence and localization of a novel FK506-binding protein to mouse chromosome
      11.
AB  - We have isolated a unique gene from a mouse JB6 epidermal cell cDNA expression
      library, termed FKBPRP, that codes for a protein having domains that share
      between 37 and 44% amino acid sequence identity and 60% similarity with members
      of the family of FK506-binding proteins. The FKBPRP protein has three repeats
      contained within its sequence that share between 48 and 58% identity to each
      other. We have localized the FKBPRP gene to mouse Chromosome 11, and crosses of
      different murine strains provided the gene order centromere--FKBPRP-Int-4-Pkca-Es
      3.

PMID- 7507078
TI  - The human insulin-like growth factor-binding protein 4 gene maps to chromosome
      region 17q12-q21.1 and is close to the gene for hereditary breast-ovarian cancer.
AB  - The gene for insulin-like growth factor-binding protein 4 (IGFBP4) codes for a
      serum protein that binds to the family of insulin-like growth factors and
      modulates their activity. It has been mapped by in situ hybridization to
      chromosome region 17q12-q21.1. We have developed a CA-repeat polymorphism from a
      cosmid clone containing IGFBP4. By linkage analysis, IGFBP4 maps to the
      chromosome 17q interval THRA1-D17S579. This interval also contains the gene for
      hereditary breast-ovarian cancer, BRCA1. Genetic recombination between IGFBP4 and
      BRCA1 places IGFBP4 centromeric to the cancer susceptibility gene and effectively
      excludes it as a candidate gene for BRCA1. IGFBP4 is, however, one of the closest
      known centromeric markers for BRCA1; the estimated recombination fraction is
      0.015. IGFBP4 and D17S579 together define a 2.8-cM interval that contains BRCA1.

PMID- 7507079
TI  - Nucleotide sequences of the RNA subunit of RNase P from several mammals.
AB  - Sequences of the RNA subunit of RNase P from five primate and two rodent species
      have been determined. The extent of the differences among these sequences and the
      corresponding RNA from human tissue correlates to known phylogenetic
      relationships. All the sequences can be drawn in a secondary structure with
      common features.

PMID- 7507080
TI  - Polymorphism of salivary esterase and alpha-amylase in the Greek population.
AB  - The genetic polymorphism of two salivary enzymes (esterase and alpha-amylase) was
      studied in individuals from eight districts of Greece. The pooled gene
      frequencies were: SetS = 0.63, SetF = 0.37, AMY1 = 0.87, AMY2 = 0.10, AMY3 =
      0.02, and AMY4 = 0.01. There was no intrapopulation heterogeneity, while there
      was a significant difference between the Greeks and the few other European
      populations studied.

PMID- 7507082
TI  - Development of second generation monoclonal antibodies recognising Lewisy/b
      antigen by anti-idiotypic immunisation.
AB  - Five new monoclonal antibodies (Mabs) recognising the Lewisy/b hapten of the IgG
      isotype have been produced following immunisation with rat anti-idiotypic
      antiserum to C14, an IgM Lewisy/b hapten Mab and boosting with C14gp200 antigen.
      They have the same fine specificity as the original Mab binding to a cell surface
      and secreted antigen preferentially expressed by colorectal tumour cells.

PMID- 7507081
TI  - Analysis of chicken CD4 by monoclonal antibodies indicates evolutionary
      conservation between avian and mammalian species.
AB  - We have created a panel of mouse monoclonal antibodies detecting different
      epitopes on avian CD4 molecule. Two-color immunofluorescence analysis shows that
      chicken peripheral alpha beta T cells are either CD4 or CD8 single positive
      whereas most gamma delta T cells are CD4-negative both in the thymus and
      peripheral tissues. Unlabeled antibody competition analysis by flow cytometry
      demonstrates that several different epitopes on chicken CD4 are recognized by
      these antibodies. Antibodies precipitate a monomeric glycoprotein from surface
      labeled chicken thymocytes and T cells with relative molecular mass (M(r) of 64
      kd as analyzed by SDS gel electrophoresis. Removal of N-linked carbohydrates by
      endoglycosidase-F increases the electrophoretic mobility and reveals the core
      protein size with M(r) of 45 kd. The anti-CD4 antibodies inhibit antigen-induced
      cellular proliferation of a keyhole limpet hemocyanin (KLH) -specific T cell
      line. They synergize in the blocking of T cell proliferation with anti-class II
      major histocompatibility complex (MHC)-specific antibodies indicating that
      chicken CD4 is involved in antigen recognition process by CD4+ T cells. We also
      show that chicken CD4 is down-modulated in a similar manner as its mammalian
      equivalent when thymocytes are stimulated in vitro with phorbol esters.
      Altogether these findings suggest functional and biochemical conservation of the
      CD4 molecule in evolution.

PMID- 7507083
TI  - Monoclonal antibody against a human sperm protein recognizes multiple epitopes on
      rabbit and human sperm and blocks sperm function.
AB  - A monoclonal antibody was raised against a human sperm protein of apparent
      molecular size of 40 kDa. Of the 6 hybridoma clones selected for study, one clone
      (B-12) was chosen for further investigations. The antibody secreted by the clone
      agglutinated human and rabbit spermatozoa in vitro. The antibody belonged to IgM
      class. In indirect immunofluorescence studies this antibody reacted to acrosome
      of living human and rabbit spermatozoa. On fixed sperm of the same species it
      recognized midpiece and parts of tail along with the acrosome. Mouse, hamster,
      guinea pig, monkey and rat sperm showed similar localization. Interaction between
      rabbit sperm and oocyte was inhibited in vitro by this antibody. On western blots
      of human and rabbit sperm extracts the antibody recognized more than one epitope.

PMID- 7507084
TI  - Monoclonal antibodies against hst-1 gene product.
AB  - Four monoclonal antibodies (MAbs) against the hst-1 gene product (hst-1 protein)
      were obtained by a somatic cell hybridization technique. The recognition sites of
      these MAbs designated HS-131, HS-210, HS-233 and HS-276 on the hst-1 protein were
      evaluated by competitive binding assay with synthetic polypeptides. HS-131 MAb
      and HS-276 MAb recognize the epitope located within the 59-73 and the 197-206
      amino acid sequences, respectively. The epitopes recognized by HS-210 and HS-233
      MAbs could not be determined, but these MAbs showed neutralizing activity against
      hst-1 protein. Using HS-131 and HS-233 MAbs, a sensitive sandwich enzyme
      immunoassay (sandwich EIA) has been developed. The assay sensitivity was 1.2-2.5
      pg/well of hst-1 protein. Acidic and basic fibroblast growth factors were not
      cross-reactive up to a concentration of 1 microgram/ml.

PMID- 7507085
TI  - Production of monoclonal antibodies recognising different epitopes present on
      insulin-like growth factor 1.
AB  - Monoclonal antibodies (MAbs) were generated against recombinant human insulin
      like growth factor 1 (IGF-1) by fusion of NS-1 myeloma cells with spleen cells
      from BALB/c X DBA mice immunised with recombinant IGF-1 and synthetic peptide
      sequences derived from the published amino acid sequence of IGF-1. MAbs were
      produced that recognised four distinct epitopes including two defined segments of
      the C and D domains. All MAbs were IgM mouse immunoglobulins. These results
      indicate the feasibility of producing MAbs to highly conserved proteins.

PMID- 7507086
TI  - Stabilization of inducible nitric oxide synthase by monoclonal antibodies.
AB  - We have produced 14 monoclonal antibodies to inducible nitric oxide synthase
      purified from rat peritoneal cytotoxic activated macrophages. None of the
      antibodies showed neutralizing activity, but some of them enhanced the enzyme
      activity through stabilization of the enzyme.

PMID- 7507087
TI  - A parametric modeling of ionic channel current fluctuations using third-order
      statistics and its application to estimation of the kinetic parameters of single
      ionic channels.
AB  - A parametric modeling of stationary ionic-channel current fluctuations (SICF's)
      using third-order cumulants is presented and its application to estimation of the
      kinetic parameters of single ionic channels is discussed. We consider the case
      where third-order cumulants of SICF's are nonzero, and where SICF's are corrupted
      by an unobservable additive colored Gaussian noise that is independent of SICF's.
      First, we construct a virtual synthesizer that yields an output whose third-order
      cumulants are equivalent to those of SICF's on a specific slice. The synthesizer
      output is expressed by the sum of N5 - 1 first-order differential equation
      systems, where N8 denotes the number of states of single ionic channels. Next,
      discretizing the synthesizer output, we derive a discrete autoregressive (AR(N8 -
      1)) process driven by the sum of N8 - 1 moving average (MA(N9 - 2)) processes.
      Then the AR coefficients are explicitly related to the kinetic parameters of
      single ionic channels, implying that the kinetic parameters can be estimated by
      identifying the ARMA coefficients using the third-order cumulants. In order to
      assess the validity of the proposed modeling and the accuracy of parameter
      estimates, Monte Carlo simulation is carried out in which the closed-open and
      closed-open-blocked schemes are treated as specific examples.

PMID- 7507089
TI  - The effect of lipoylation on CD4 T-cell recognition of the 19,000 MW
      Mycobacterium tuberculosis antigen.
AB  - The mechanisms contributing to the dominant and degenerate recognition of the N
      terminal region of the Mycobacterium tuberculosis 19,000 MW protein have been
      investigated. Using polyclonal and cloned T cells it was found that the
      apparently promiscuous response to the N-terminal peptide was due to the presence
      of multiple epitopes recognized in the context of different HLA determinants.
      This finding did not, however, explain the concentration of T-cell recognition on
      this part of the molecule. The 19,000 MW antigen is a lipoprotein, which raised
      the possibility that presence of a lipidation motif preceded by a signal peptide
      influenced the processing and presentation of the protein. Modified peptides
      covalently attached to lipid moieties were, therefore, tested on both polyclonal
      and cloned T cells. It was found that whilst lipoylation enhanced polyclonal T
      cell recognition, the effect on cloned T cells was variable and depended on their
      epitope specificity and restricting HLA determinants. This suggested that whilst
      lipoylation may enhance some aspect of signalling for polyclonal T cells it does
      not affect the presentation of peptide to T-cell clones. The explanation for the
      immunodominance of the N-terminal region may, therefore, lie in some aspect of
      its processing.

PMID- 7507088
TI  - In vitro primary sensitization and restimulation of hapten-specific T cells by
      fresh and cultured human epidermal Langerhans' cells.
AB  - We examined the capacity of human Langerhans's cells (LC) to sensitize autologous
      T cells to the trinitrophenyl hapten (TNP) in vitro. Two-day cultured Langerhans'
      cells, but not freshly prepared Langerhans' cells, can induce in vitro primary
      proliferative reactions to the TNP hapten. Using a CD45RA+ naive T-cell subset,
      similar results were found, therefore making the possibility of a previous in
      vivo T-cell contact with the hapten unlikely. The primary in vitro response was
      strongly inhibited by monoclonal antibodies to major histocompatibility complex
      (MHC) class I and II, CD4 antigens and ICAM-1 and LFA-3 adhesion molecules.
      Furthermore, we found that fresh LC can prime T cells to TNP, as revealed by a
      significant secondary T-cell proliferation after restimulation of the recovered T
      lymphocytes by fresh hapten-modified autologous LC. Nevertheless, the ability of
      these fresh LC to stimulate in vitro secondary hapten-specific T-cell
      proliferation was very limited in comparison with that of 2-day incubated
      Langerhans' cells. After secondary stimulation with TNP-cultured LC, sensitized T
      cells could be non-specifically expanded without losing hapten specificity. The
      TNP-specific T-cell lines were mostly of the CD4+ phenotype. The present findings
      extend previous studies in the mouse, showing that culture LC are potent antigen
      presenting cells (APC) in primary hapten-dependent proliferation assays.
      Furthermore, this in vitro priming assay, using cultured human Langerhans' cells
      as APC, might be useful to analyse the early steps of T-cell sensitization and
      subsequently to develop in vitro predictive tests allowing detection of
      sensitizing compounds.

PMID- 7507090
TI  - CD14 and tolerance to lipopolysaccharide: biochemical and functional analysis.
AB  - To evaluate the role of the high-affinity monocyte receptor for
      lipopolysaccharide (LPS), CD14, in the process of tolerance to LPS, the human
      monocytic cell line Mono-Mac-6 was cultured in the absence or presence of
      different amounts of LPS. The kinetics of CD14 modulation in these cells showed
      an initial 4-day period characterized by increased cell-surface expression, rate
      of biosynthesis (peaking at 48 hr) and release of its soluble forms (sCD14) which
      correlated with the amount of LPS in the culture. At this time, tolerance to LPS
      was already established, as measured by tumour necrosis factor-alpha (TNF-alpha)
      induction, it was LPS dose dependent and persisted up to 15 days. LPS also
      reduced the cell proliferation rate in a dose-dependent manner. After 8 days and
      up to 15 days, the CD14 biosynthesis, cell-surface expression and release of
      sCD14 inversely correlated with the level of LPS in the culture. The 48-hr LPS
      pretreated cells showed a slightly decreased CD14 affinity for LPS, a relative
      high number of CD14 molecules per cells, and desensitization also to a phorbol 12
      myristate 13-acetate (PMA) challenge. An anti-CD14 monoclonal antibody (mAb)
      protected the cells from tolerization when added at the beginning of culture, as
      revealed by challenge with LPS and PMA. The data indicate that in this model
      tolerization to LPS (1) precedes CD14 down-modulation, (2) operates by alteration
      of the receptor affinity for LPS and by a mechanism which affects a protein
      kinase C (PKC)-dependent signalling pathway, and (3) that CD14 plays a critical
      role in the establishment of tolerance to LPS. In addition, analysis of the data
      suggests the existence of a PKC-independent signalling pathway for LPS
      tolerization and a CD14-independent mechanism for establishing tolerance.

PMID- 7507091
TI  - Biochemical and functional alterations induced by CD23 ligation in the human
      promonocytic cell line U937.
AB  - The early events triggered in interleukin-4 (IL-4)-stimulated U937 cells by
      ligation of CD23/Fc epsilon RII with specific monoclonal antibodies (mAb) were
      analysed, as a model of the action of this molecule on the differentiation of
      promonocytic cells. As well as IL-4-activated human monocytes, addition of anti
      CD23 mAb to IL-4-treated U937 cells triggered cAMP accumulation but did not evoke
      significant polyphosphoinositide hydrolysis. However, by a
      microspectrofluorometric technique allowing single cell analysis, anti-CD23 mAb
      was found to elicit calcium mobilization in these cells. In addition, the
      treatment induced phenotypic alterations in these cells, as evidenced by the
      acquisition of the monocyte marker CD14 and the increase of the alpha-chain
      (CD11a) and of the common beta-chain (CD18) of the leucocyte function-associated
      antigen 1 (LFA-1) family antigens. Although weaker than in monocytes, CD23
      ligation evoked a small secretion of the pro-inflammatory mediators IL-6 and
      thromboxane B2. These data suggest that a significant maturation of promonocytic
      cells towards a more mature monocytic phenotype can be achieved through
      successive exposure to IL-4 and CD23 ligation.

PMID- 7507092
TI  - Induction of neutrophil homotypic adhesion via sialophorin (CD43), a surface
      sialoglycoprotein restricted to haemopoietic cells.
AB  - CD43 is a cell-surface sialoglycoprotein which is selectively expressed on lympho
      haemopoietic cells. We studied the effects of three CD43 antibodies (6E5, 6F5 and
      10G7) on human neutrophils and found that all three monoclonal antibodies (mAb)
      induced significant homotypic adhesion involving more than 50% of cells.
      Monovalent Fab fragments of CD43 mAb had no such effect but became equally
      effective upon cross-linkage with F(ab')2 sheep anti-mouse immunoglobulin (Ig)
      antibodies. The homotypic adhesion induced by CD43 antibodies was dependent on
      divalent cations, energy, temperature and an intact cytoskeleton, but not on de
      novo protein synthesis. Homotypic adhesion could be inhibited by mAb to CD11b,
      CD18 and CD54, indicating an involvement of the beta 2 integrin cyto-adhesion
      pathway. Additionally, oxidative burst formation was observed with intact CD43
      mAb. No such effect was seen with monomeric or cross-linked Fab fragments. This,
      together with the observation that burst formation unlike adhesion induction
      could be completely abolished with Fc gamma RII, but not with Fc gamma RIII
      antibody fragments, suggests that in burst induction, heterologous cross-linkage
      with Fc gamma RII is involved. A Ca2+ increase with CD43 antibodies was not
      detectable. Adhesion induction was unaffected by H7, chelerythrin, staurosporine
      or lavendustin A, but was completely ablated by sphingosine and herbimycin A.
      This suggests an involvement of tyrosine kinases but not of protein kinase C in
      the signal transduction cascade leading to homotypic adhesion. CD43 mAb-induced
      burst formation differed from adhesion induction in that it could be additionally
      inhibited with staurosporine and lavendustin A.

PMID- 7507093
TI  - Immunolocalization and characterization of the rat analogue of human CD59 in
      kidney and glomerular cells.
AB  - CD59, a potent inhibitor of the human membrane attack complex (MAC) of
      complement, is present on many different tissues throughout the body. Recently we
      identified and characterized the rat analogue of CD59 and produced a number of
      monoclonal antibodies (mAb). We have now used these antibodies to demonstrate, by
      immunofluorescence microscopy, that rat CD59 was widely expressed in the rat
      kidney. Staining of renal sections revealed the presence of rat CD59 in abundance
      in the glomerulus, collecting ducts and distal tubules. Staining was abolished by
      treatment of sections with phosphatidylinositol-specific phospholipase C (PIPLC).
      Rat mesangial cells also stained strongly for rat CD59, giving an intensely
      granular staining pattern. In complement attack experiments the cultured
      mesangial cells were rendered more susceptible to lysis by rat or human
      complement after preincubation with the anti-inhibitor mAb. The results
      demonstrate that the rat analogue of CD59 is present and functionally active in
      rat renal tissue. The protective effect of CD59 against MAC-mediated tissue
      injury can now be examined in rat models of human renal disease.

PMID- 7507095
TI  - Neurological assessment at three months as a predictor for developmental outcome
      in high risk infants.

PMID- 7507097
TI  - Technology briefs from the Conseil d'Evaluation des Technologies de la Sante du
      Quebec (CETS). Diathermy and balloon dialatation treatment of benign prostatic
      hypertrophy.

PMID- 7507098
TI  - Prostacyclin analogs suppress the synthesis of tumor necrosis factor-alpha in LPS
      stimulated human peripheral blood mononuclear cells.
AB  - Recent reports have shown that prostaglandin E2 (PGE2) is able to suppress
      lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-alpha
      (TNF-alpha). In the present study we compared PGE2 with prostacyclin (PGI2)
      analogs in their potency to influence LPS-stimulated production of interleukin-1
      beta (IL-1 beta) and TNF-alpha by human mononuclear cells (MNC). Our results
      show, that the stable analogs of PGI2, iloprost and cicaprost, markedly suppress
      TNF-alpha synthesis in LPS-stimulated MNC without effect on IL-1 beta production.
      Although there was no significant difference in maximal suppression of TNF-alpha,
      iloprost and cicaprost reached suppression to 50% of control at 20-fold lower
      concentrations than PGE2. The ID50 for iloprost and cicaprost were 8 nM and 5 nM,
      respectively, compared to 125 nM for PGE2. Moreover, the prostacyclin analogs as
      well as PGE2 suppressed LPS-induced production of TNF-alpha in Mono Mac 6 cells,
      a permanent human cell line with characteristics of mature monocytes. Suppression
      of TNF-alpha synthesis by cicaprost and PGE2 is probably mediated by an increased
      intracellular cAMP formation. We were able to show elevated cAMP levels with 1
      microM and 10 microM of PGE2 and cicaprost in this system. The suppression of TNF
      alpha synthesis may add to the beneficial effects of iloprost reported in animal
      models of acute respiratory distress syndrome (ARDS) and may offer a therapeutic
      approach in TNF-alpha mediated pathologic processes.

PMID- 7507094
TI  - Therapeutic effect of granulocyte colony-stimulating factor (G-CSF) on the
      protection against Listeria infection in SCID mice.
AB  - Anti-listerial activity in SCID mice as well as in control C.B-17 mice was
      augmented by granulocyte colony-stimulating factor (G-CSF). After 1 x 10(3)
      colony-forming units of Listeria monocytogenes (strain EGD) were intravenously
      inoculated, mice were intraperitoneally injected with G-CSF at a daily dose of
      500 micrograms/kg for 5 days. The numbers of viable bacteria in the liver were
      significantly lower in G-CSF-treated SCID and C.B-17 mice than in non-treated
      mice. The surface marker analyses on gamma delta T-cell receptor (TcR), Mac-1 and
      F4/80, and dichlorofluorescein oxidative activity, showed a possible contribution
      of activated neutrophils, but not gamma/delta T cells nor activated macrophages,
      to the augmentation of anti-listerial activity in SCID mice. This study is one of
      the first reports on the anti-microbial effect of G-CSF in therapeutic use.

PMID- 7507096
TI  - Assessment of screening tests for transfusion-associated non-A non-B hepatitis.
AB  - Non-A non-B hepatitis is the most common serious sequela of blood transfusion,
      and its screening has become an essential goal of blood transfusion centers.
      Before 1989, two surrogate screening tests (for alanine aminotransferase and for
      antibody to hepatitis B core antigen) were used; in 1989, a direct test for the
      antibody to hepatitis C virus (the main agent of this hepatitis) was developed.
      The French National Agency for the Development of Medical Evaluation undertook an
      investigation to determine the optimal prevention strategy for posttransfusion
      non-A and non-B hepatitis (PTH). A detailed literature review was performed,
      complemented by expert group opinion. The performance of each test was derived
      indirectly by calculating the number of cases of PTH averted by each test.
      Hepatitis C virus testing is probably the most promising strategy, but different
      policies can be developed given the uncertainties of scientific data. Cost
      considerations should be taken into account in identifying the best screening
      strategy.

PMID- 7507099
TI  - Characterization of K currents in cultured human corporal smooth muscle cells.
AB  - In order to gain more mechanistic insight into the regulation of corporal smooth
      muscle tone, we conducted electrophysiological studies on homogeneous explant
      cell cultures of human corpus cavernosum smooth muscle. Patch clamp analyses in
      the whole cell mode revealed a mean resting potential of -43 +/- 4.9 m V (n = 12
      cells). Large whole cell outward K currents were very prominent in these cells,
      and ranged from 0.5 to 1.5 nA. In some cells, a transient, voltage-dependent A
      current accounted for a significant portion of the observed whole cell currents.
      Furthermore, stimulation with the calcium channel agonist BAY K 8644 or the K
      channel agonist pinacidil doubled the magnitude of the whole cell K current, as
      would be expected for maxi-K (KCa) and metabolically gated K channels (KATP),
      respectively. Single channel recordings in the detached patch mode consistently
      revealed the presence of at least two K channels: 1) a KCa channel, with a
      conductance of approximately 190 pS; and 2) a putative delayed rectifier channel
      with a conductance of approximately 50 pS. Furthermore, all channel types showed
      some degree of voltage and/or calcium sensitivity. In conclusion, the large
      magnitude of the whole cell K currents and the observed K channel heterogeneity
      indicate a potentially important role for these channels in modulating corporal
      smooth muscle tone.

PMID- 7507100
TI  - Gastricsin-mediated proteolytic degradation of human seminal fluid proteins at pH
      levels found in the human vagina.
AB  - The proteolytic degradation of human seminal fluid proteins at acidic conditions
      has been investigated. Upon acidification to the pH level of the human vagina,
      autoproteolysis of most seminal fluid proteins occurred after 30 minute of
      incubation at 37 degrees C. The degradation was unaffected by inhibitors of
      serine, thiol, or metallo proteases, whereas pepstatin prevented any proteolysis.
      The proteins in seminal fluid depleted of the aspartic protease progastricsin did
      not degrade upon acidification. Readdition of the progastricsin restored the
      autoproteolytic ability of seminal fluid. Prostate-specific antigen, prostatic
      acid phosphatase, and Zn-alpha 2-glycoprotein are quickly degraded; albumin,
      transferrin, and lactoferrin are degraded more slowly. The low molecular weight
      fragments of semenogelin I and II and especially beta-microseminoprotein are
      somewhat resistant to proteolysis. These observations strongly suggest that the
      aspartic protease progastricsin is responsible for the autoproteolysis of seminal
      fluid proteins under acidic conditions. This suggests that the function of the
      enzyme is to degrade seminal fluid proteins deposited in the vagina; this in turn
      may decrease the antigenic load in the vagina and prevent immuno-infertility.

PMID- 7507101
TI  - The acrosome reaction-inducing effect of human follicular and oviductal fluid.
AB  - The human sperm acrosome reaction (AR) can be induced in vitro by a variety of
      naturally occurring and synthetic compounds. The present investigation determined
      the effect of human natural cycle periovulatory follicular (hFF) and oviductal
      fluids (hOF) on the human sperm AR in dose-response fashion using the synchronous
      AR assay. When hFF (30% v/v) or hOF (40% v/v) was added to non-capacitated
      spermatozoa, no significant (P > 0.05) increase in the % AR was detected in
      comparison to the non-treatment control. When either of these compounds was added
      (10%, 20%, and 30% v/v hFF; 20%, 30%, and 40% v/v hOF) to capacitated spermatozoa
      (3 hour incubation), a significant (P < 0.05) stimulation of the AR was detected.
      Bovine oviductal fluid (bOF) was tested (20%, 30%, and 40% v/v) to determine if
      it might have an effect similar to hOF. In contrast to hOF, the highest
      concentration of bOF (40% v/v) tested failed to stimulate a significant (P >
      0.05) increase in the % AR of capacitated spermatozoa in comparison to control.
      Inhibitors of protein kinases A (KT5720) and C (calphostin C) were tested to
      determine their effects on the hFF-induced AR. In comparison to hFF treatment
      alone, the kinase A inhibitor KT5720 (50 nM, 100 nM) prevented hFF (20%)
      stimulation of the AR when added at the end of the capacitation period and 5
      minutes prior to the addition of inducer. Similarly, the kinase C inhibitor
      calphostin C (50 nM, 100 nM) prevented hFF (20%) stimulation of the AR. The
      present data demonstrate that periovulatory hFF and hOF stimulate the human sperm
      AR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507102
TI  - Genetics of galactose metabolism of Erwinia amylovora and its influence on
      polysaccharide synthesis and virulence of the fire blight pathogen.
AB  - Galactose metabolism mutants of Erwinia amylovora were created by transposon
      insertions and characterized for their growth properties and interaction with
      plant tissue. The nucleotide sequence of the galE gene was determined. The gene,
      which encodes UDP-galactose 4-epimerase, shows homology to the galE genes of
      Escherichia coli, Neisseria gonorrhoeae, Rhizobium meliloti, and other gram
      negative bacteria. Cloned DNA with the galE and with the galT and galK genes did
      not share borders, as judged by the lack of common fragments in hybridization
      with chromosomal DNA. These genes are thus located separately on the bacterial
      chromosome. In contrast to the gal operon of E. coli, the galE gene of E.
      amylovora is constitutively expressed, independently of the presence of galactose
      in the medium. The function of the galE gene but not of the galT or galK gene is
      required for bacterial virulence on pear fruits and seedlings. In the absence of
      galactose, the galE mutant was deficient in amylovoran synthesis. Subsequently,
      the galE mutant cells elicited host defense reactions, and they were not stained
      by fluorescein isothiocyanate-labelled lectin, which efficiently binds to
      amylovoran capsules of E. amylovora. The mutation affected the side chains of
      bacterial lipopolysaccharide, but an intact O antigen was not required for
      virulence. This was shown with another mutant, which could be complemented for
      virulence but not for side chain synthesis of lipopolysaccharide.

PMID- 7507103
TI  - Differential expression of an E-selectin ligand (SLex) by two Chinese hamster
      ovary cell lines transfected with the same alpha (1,3)-fucosyltransferase gene
      (ELFT).
AB  - The mammalian cDNA encoding alpha (1,3)-fucosyltransferase (alpha (1,3)Fuc-T)
      termed ELAM-1 ligand fucosyltransferase (ELFT) or Fuc-TIV was previously cloned
      by three groups who reported different results from transfection studies Goelz et
      al. (Goelz, S. E., Hession, C., Goff, D., Griffiths, B., Tizard, R., Newman, B.,
      Chi-Rosso, G., and Lobb, R. (1990) Cell 63, 1349-1356) found that Chinese hamster
      ovary (CHO) cells expressing the ELFT cDNA had alpha (1,3)Fuc-T activity and were
      able to bind to E-selectin. In contrast, Lowe et al. (Lowe, J. B., Kukowska
      Latallo, J. F., Nair, R. P., Larsen, R. D., Marks, R. M., Macher, B. A., Kelly,
      R. J., and Ernst, L. K. (1991) J. Biol. Chem. 266, 17467-17477) and Kumar et al.
      (Kumar, R., Potvin, B., Muller, W. A., and Stanley, P. (1991) J. Biol. Chem. 266,
      21777-21783) found no binding to E-selectin of CHO transfectants expressing the
      same alpha (1,3)Fuc-T gene; nor did the latter transfectants synthesize a known E
      selectin ligand, sialylated Lex (SLex), although they had substantial alpha
      (1,3)Fuc-T activity. We now show that these discrepant results were due to a
      difference between the parental CHO cell lines. Following transfection of ELFT
      cDNA into Pro-5 or dihydrofolate reductase (DHFR)- CHO cells, only the DHFR-
      transfectants expressed SLex and bound to E-selectin. Indirect evidence from
      monoclonal antibody and lectin binding studies indicates that the range of
      carbohydrate structures synthesized by the Pro-5 and DHFR- CHO cell lines
      differs. Since DHFR-/ELFT transfectants expressed cell surface SLex but
      transferred fucose poorly to sialylated substrates in vitro, ELFT may be able to
      fucosylate a complex carbohydrate missing from Pro-5 cells. Alternatively, either
      CHO line may have an activity (such as an alpha (2,3)-sialyltransferase), that
      modifies alpha (1,3)-fucosylated lactosamines.

PMID- 7507104
TI  - Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated
      protein kinase signaling cascade in cardiac myocytes. The potential role of the
      cascade in the integration of two signaling pathways leading to myocyte
      hypertrophy.
AB  - Maximally effective concentrations of endothelin-1 (ET-1), acidic FGF (aFGF), or
      12-O-tetradecanoylphorbol-13-acetate (TPA) activated mitogen-activated protein
      kinase (MAPK) by 3-4-fold in crude extracts of myocytes cultured from neonatal
      rat heart ventricles. Maximal activation was achieved after 5 min. Thereafter,
      MAPK activity stimulated by ET-1 or aFGF declined to control values within 1-2 h,
      whereas activation by TPA was more sustained. Two peaks of MAPK activity (a 42-
      and a 44-kDa MAPK) were resolved in cells exposed to ET-1 or aFGF by fast protein
      liquid chromatography on a Mono Q column. One major and one minor peak of MAPK
      kinase (MAPKK) was stimulated by ET-1 or aFGF. Cardiac myocytes expressed protein
      kinase C (PKC)-alpha, -delta, -epsilon and -zeta as shown immunoblotting.
      Exposure to 1 microM TPA for 24 h down-regulated PKC-alpha, -delta, and -epsilon,
      but not PKC-zeta. This maneuver wholly abolished the activation of MAPK on re
      exposure to TPA but did not affect the response to aFGF. The effect of ET-1 was
      partially down-regulated. ET-1 stimulated phospho[3H]inositide hydrolysis 18
      fold, whereas aFGF stimulated by only 30%. Agonists which initially utilize
      dissimilar signaling pathways may therefore converge at the level of MAPKK/MAPK
      and this may be relevant to the hypertrophic response of the heart.

PMID- 7507105
TI  - Identification and mutation of primary and secondary proteolytic cleavage sites
      in murine stem cell factor cDNA yields biologically active, cell-associated
      protein.
AB  - Phenotypic abnormalities of melanocytes, germ cells, and hematopoietic cells of
      Steel mice demonstrate the critical role of stem cell factor (SCF) in
      development. Production of SCF in the hematopoietic microenvironment as either a
      membrane-associated or soluble factor leads to pleiotropic effects on
      hematopoietic stem and progenitor cells and significant effects on the production
      of erythroid cells. Although the production of these two forms of SCF is highly
      regulated, the physiologic role(s) of membrane-associated and soluble SCF remain
      unclear. We have demonstrated that the generation of soluble murine SCF by murine
      stromal cells derived from the fetal hematopoietic microenvironment is dependent
      on two distinct proteolytic cleavage sites. The primary site in exon 6 is
      preferentially utilized in these cells. The secondary site located in exon 7 is
      utilized only in the absence of the primary site. Proteolytic processing at this
      secondary site appears to be species-specific, since the human protein sequence
      diverges at this site, and protein expressed from the human cDNA encoding this
      site in murine stromal cells remains largely membrane-associated. Site-directed
      mutagenesis of the murine SCF cDNA encoding both proteolytic cleavage sites leads
      to the generation of membrane-associated and biologically active SCF on murine
      stromal cells. These results suggest that the regulation of processing of the
      secondary proteolytic cleavage site could play a critical role in the function of
      membrane-associated SCF protein.

PMID- 7507106
TI  - Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine
      macrophage cell line. Implications for regulation of nitric oxide production.
AB  - In macrophages and other cell types, bacterial lipopolysaccharide and certain
      cytokines stimulate nitric oxide (NO) production via expression of the inducible
      isoform of nitric oxide synthase (NOS). Citrulline, which is the coproduct of NOS
      catalyzed metabolism of arginine, can be recycled to arginine by the action of
      argininosuccinate synthetase and argininosuccinate lyase, which are present at
      high levels in hepatocytes and renal tubular cells but normally at very low
      levels in other cell types such as macrophages. The present study demonstrates
      that lipopolysaccharide and interferon-gamma, which induce NOS in the murine
      macrophage cell line RAW 264.7, also coinduce activity and mRNA for
      argininosuccinate synthetase, which is limiting for arginine synthesis.
      Argininosuccinate lyase activity and mRNA abundance are unaffected. Induction of
      argininosuccinate synthetase is not blocked by NG-monomethyl-L-arginine, a potent
      inhibitor of NOS, indicating that argininosuccinate synthetase induction is not
      the consequence of depleting cellular arginine levels by NOS. Because plasma
      levels of arginine are limiting for NO synthesis, enhanced cellular capacity to
      regenerate arginine from citrulline could play a significant role in regulating
      NO production, especially under conditions where the inducible isoform of NOS is
      expressed.

PMID- 7507107
TI  - Modulation of HIV-1 reverse transcriptase function in "selectively deleted"
      p66/p51 heterodimers.
AB  - A contribution of the 51-kDa subunit of human immunodeficiency virus type-1
      reverse transcriptase to activities of the parental heterodimer (p66/p51) was
      assessed in "selectively deleted" heterodimers whose p51 component contained C
      terminal truncations of 13, 19, or 25 residues. Analyses included (i) efficiency
      of reconstitution into heterodimer, (ii) retention of polymerase and ribonuclease
      H (RNase H) function, and (iii) interaction with the HIV replication primer,
      tRNA(Lys,3). Our data suggest that these features of heterodimer reverse
      transcriptase can be modulated by the extent of the C-terminal p51 deletion.
      Severely impaired tRNA binding in a selectively deleted heterodimer whose 51-kDa
      subunit lacks 13 residues, despite retention of enzymatic functions, strengthens
      arguments for p51 involvement in tRNA binding.

PMID- 7507108
TI  - Differential E-selectin-dependent adhesion efficiency in sublines of a human
      colon cancer exhibiting distinct metastatic potentials.
AB  - Previously we have shown that high metastatic colonic carcinoma cells express
      relatively more lamp molecules and sialyl Le(x) structures on the cell surface
      than their corresponding low metastatic counterparts (Saitoh, O., Wang, W.-L.,
      Lotan, R., and Fukuda, M. (1992) J. Biol. Chem. 267, 5700-5711). In the present
      study, we extended these findings by testing whether these high and low
      metastatic colonic carcinoma cells differ in their adhesion efficiency to E
      selectin-expressing cells. First, it was found that the high metastatic cells, as
      compared to their low metastatic counterparts, bind more efficiently to activated
      human endothelial cells that express E-selectin. This was also true when the
      adhesion was tested for Chinese hamster ovary cells stably expressing E-selectin.
      In addition, it was found that the high metastatic cells also adhere more
      efficiently to mouse endothelioma cells after activation with interleukin-1 beta.
      It was also shown that the adhesion can be inhibited by soluble lamp-1 or soluble
      leukosialin that contain sialy Le(x) termini. The inhibition was not, however,
      observed when these soluble glycoproteins lack sialyl Le(x) structures. The
      results indicate that the efficiency of the E-selectin-mediated binding of
      colonic carcinoma cells to human and mouse endothelial cells correlates with the
      metastatic potential of the cells and suggest that this adhesive event may be one
      of the critical factors for the metastatic spread of tumor cells. Soluble forms
      of leukosialin or lamp-1 may be useful as therapeutic agents for the inhibition
      of E-selectin-mediated binding to tumor cells.

PMID- 7507109
TI  - Classification of alpha 2-macroglobulin-cytokine interactions based on affinity
      of noncovalent association in solution under apparent equilibrium conditions.
AB  - alpha 2-Macroglobulin (alpha 2M) binds numerous cytokines; however, since binding
      affinities have not been determined, it is difficult to compare various alpha 2M
      cytokine interactions or predict whether alpha 2M-cytokine complexes will form in
      the presence of other cytokine-binding macromolecules. In this investigation, we
      used a novel method to demonstrate that transforming growth factor-beta 1 (TGF
      beta 1), TGF-beta 2, nerve growth factor-beta (NGF-beta), platelet derived growth
      factor-BB (PDGF-BB), tumor necrosis factor-alpha (TNF-alpha), and basic
      fibroblast growth factor (bFGF) reversibly associate with alpha 2M-methylamine to
      form noncovalent complexes. Apparent equilibrium was achieved in less than 15
      min. Noncovalent alpha 2M-cytokine complexes were converted into covalent
      complexes; however, this occurred slowly. Therefore, a rapid equilibrium
      assumption was applied and equilibrium dissociation constants were determined
      using a single binding site model. KD values for the binding of cytokines to
      alpha 2M-methylamine varied by 2 orders of magnitude. The rank order of affinity
      was TGF-beta 2 (13 +/- 2 nM) > TGF-beta 1, NGF-beta > PDGF-BB > or = bFGF > TNF
      alpha. Native alpha 2M bound TGF-beta 1, TGF-beta 2, NGF-beta, PDGF-BB, and TNF
      alpha. Interferon-gamma did not bind to native alpha 2M or alpha 2M-methylamine.
      Each cytokine bound native alpha 2M with lower affinity than alpha 2M-methylamine
      except for TGF-beta 2 which bound both forms with equal affinity. In non
      equilibrium systems, alpha 2M-methylamine appeared to bind more TGF-beta 2 due to
      the more rapid dissociation of TGF-beta 2-native alpha 2M complex. The
      classification of alpha 2M-cytokine complexes according to binding affinity
      should predict which complexes are most likely to form in cell culture and under
      various conditions in vivo.

PMID- 7507110
TI  - Neutral sphingomyelinase action stimulates signal transduction of tumor necrosis
      factor-alpha in the synthesis of cholesteryl esters in human fibroblasts.
AB  - We have investigated biochemical mechanisms of tumor necrosis factor (TNF)-alpha
      signaling in cultured human skin fibroblasts. We found that TNF-alpha signaling
      may involve activation of a cell membrane neutral sphingomyelinase (N-SMase) in
      that within 2.5-5 min of treatment of cells with TNF-alpha there was a 2-fold
      increase in the activity of N-SMase compared to control. This reaction led to the
      hydrolysis of sphingomyelin as evidenced by a decrease in sphingomyelin mass and
      in the radioactivity associated with [14C]choline-labeled sphingomyelin. This was
      accompanied by a 4-fold increase in the formation of cholesteryl [14C]oleate
      within 2.5 min of incubation with TNF-alpha. This reaction also stimulated the
      mobilization of cell surface-associated [3H]cholesterol and its utilization in
      the synthesis of [3H]cholesteryl esters via acyl coenzyme-A cholesterol
      acyltransferase (ACAT). Gas chromatographic analysis revealed that the cellular
      level of cholesteryl esters increased about 2.5-3-fold following treatment with
      TNF-alpha compared to control. Cholesteryl ester synthesis was compromised upon
      incubation of cells with antibody against N-SMase and remained unaltered with TNF
      beta and fibroblast growth factor. Furthermore, TNF-alpha-mediated stimulation of
      cholesteryl ester synthesis was compromised by incubation of cells with an
      inhibitor of ACAT. These findings suggest a possible biological role of N-SMase
      in the signal transduction of TNF-alpha in the synthesis of cholesteryl esters in
      human fibroblasts.

PMID- 7507111
TI  - O-glycosylation mimics N-glycosylation in the 16-kDa fragment of bovine pro
      opiomelanocortin. The major O-glycan attached to Thr-45 carries SO4-4GalNAc beta
      1-4GlcNAc beta 1-, which is the archetypal non-reducing epitope in the N-glycans
      of pituitary glycohormones.
AB  - The NH2-terminal domain of pro-opiomelanocortin, designated as the 16-kDa
      fragment, is highly conserved throughout the vertebrate family and is likely
      therefore to have an important functional role. Bovine 16-kDa fragment is a 77-
      residue glycopeptide, which has been found to be glycosylated at threonine 45 and
      asparagine 65. Available evidence suggests that glycoforms lacking glycans at the
      O-linked site are processed in the intermediate pituitary at -Arg49-Lys50- to
      give the residue 1-49 amino-terminal peptide and a carboxyl-terminal glycopeptide
      referred to as Lys1 gamma 3-melanotropin. Glycoforms carrying O-glycans remain
      unprocessed in the intermediate pituitary. Thus O-glycosylation is likely to play
      an important role in controlling the fate of the NH2-terminal portion of pro
      opiomelanocortin, thereby affecting the biological events that are influenced by
      peptides and glycopeptides derived from this domain. In a recent study
      (Siciliano, R. A., Morris, H. R., McDowell, R. A., Azadi, P., Rogers, M. E.,
      Bennett, H. P. J., and Dell, A. (1993) Glycobiology 3, 225-239), we sequenced the
      N-glycans attached to Asn-65 of bovine 16-kDa fragment and demonstrated that the
      acidic components contain, in addition to neutral antennae, a single SO4-4GalNAc
      beta 1-4GlcNAc beta 1- antenna, which is characteristic of the pituitary
      glycohormone N-glycans (Baenziger, J. U., and Green, E. D. (1988) Biochim.
      Biophys. Acta 947, 287-306). We now report the structural characterization of the
      O-linked oligosaccharides found in bovine 16-kDa fragment. The major component,
      which constitutes about 80% of the O-glycan population, is a novel sulfated
      tetrasaccharide, which carries the same sulfated epitope as the N-glycans. This
      is the first time that the SO4-4GalNAc beta 1-4GlcNAc beta 1- moiety has been
      observed in O-glycans, and it raises the interesting possibility that the beta-N
      acetylgalactosaminyltransferase responsible for the addition of N
      acetylgalactosamine to the pituitary glycohormones (Smith, P. L., and Baenziger,
      J. U. (1988) Science, 242, 930-933) might be capable of glycosylating both N- and
      O-linked acceptors.

PMID- 7507112
TI  - Phosphorylation of human erythrocyte band 3 by endogenous p72syk.
AB  - The anion transporter, band 3, is the major tyrosine kinase substrate in both red
      cell membranes and intact human erythrocytes. Using antibodies to various protein
      tyrosine kinases, we found that p72syk and p56/53lyn are present in human red
      cells, while p56lck, pp60src, p59fyn, and p55blk are absent. Treatment of intact
      red cells with a combination of vanadate and hydrogen peroxide dramatically
      increased the tyrosine phosphorylation of band 3. This treatment increased the
      tyrosine kinase activity of p72syk and decreased the activity of p56/53lyn in
      immune complex kinase assays. Band 3 was found to be associated in immune
      complexes with p72syk but not with p56/53lyn. These findings suggest that p72syk
      is responsible, at least in part, for the tyrosine phosphorylation of band 3 in
      human erythrocytes.

PMID- 7507113
TI  - A mechanism for divalent cation regulation of beta 3-integrins.
AB  - Integrins alpha IIb beta 3 and alpha V beta 3 mediate numerous cell-matrix and
      cell-cell contacts. Both integrins contain multiple divalent cation-binding
      motifs that regulate ligand binding. Here, we elucidate a major difference in the
      regulation of alpha IIb beta 3 and alpha V beta 3 by divalent ions. Fibrinogen
      binding to alpha IIb beta 3 in Ca(2+)-containing buffer is rapid, with an
      apparent association rate constant (k1app) of 8.2 x 10(5) M-1 s-1, but Ca2+ does
      not support association between fibrinogen and alpha V beta 3. Interestingly,
      Mn2+ supports fibrinogen binding to both integrins, albeit with a relatively slow
      association rate (k1app = 10(4) M-1 s-1). This influence of divalent ions on
      ligand association rates accounts for the opposite divalent ion requirements for
      platelet aggregation and tumor cell adhesion to fibrinogen. Furthermore, the
      regulation of fibrinogen binding to alpha V beta 3 is complex when both Ca2+ and
      Mn2+ are present. Physiological concentrations of Ca2+ completely ablated
      adhesion. Kinetic analysis demonstrated that Ca2+ is a mixed-type inhibitor of
      Mn(2+)-supported fibrinogen binding to alpha V beta 3. Consequently, the data
      presented here suggest a mechanism in which two separate cation-binding sites
      regulate ligand binding to beta 3-integrins.

PMID- 7507114
TI  - Characterization of the calmodulin-binding domain of rat cerebellar nitric oxide
      synthase.
AB  - Nitric oxide (NO) has recently been identified as an intercellular messenger
      which is involved in the regulation of neurotransmission, vasorelaxation, and
      cytotoxicity. In cerebellum and endothelium this compound is synthesized by
      "constitutive" nitric oxide synthases (NOS); these are Ca(2+)-calmodulin (CaM)
      dependent enzymes. A potential CaM-binding domain for the CaM-dependent NOS has
      previously been identified in the gene sequence. In this work, a synthetic 23
      residue peptide encompassing the putative CaM-binding domain of rat cerebellar
      NOS was studied. The constitutive NOS peptide binds to CaM in a calcium-dependent
      manner with 1:1 stoichiometry as determined by polyacrylamide gel electrophoresis
      of the peptide-CaM complex in 4 M urea. Circular dichroism studies showed that
      the peptide binds to CaM in an alpha-helical conformation. Binding of the
      constitutive NOS peptide inhibits the stimulatory effect of CaM on cyclic
      nucleotide phosphodiesterase. From competition experiments between the peptide
      and phosphodiesterase we have determined a Kd of 2.2 nM for the peptide-CaM
      complex. Two-dimensional NMR and circular dichroism studies were used to
      determine the structure of the peptide in aqueous solution. In addition, the
      effect of increasing amounts of trifluoroethanol on the peptide structure was
      investigated. It was found that the peptide can adopt an alpha-helical structure
      which bears close resemblance to the structure of the CaM-bound form of the CaM
      binding domains of myosin light chain kinases.

PMID- 7507115
TI  - Strand displacement activity of the human immunodeficiency virus type 1 reverse
      transcriptase heterodimer and its individual subunits.
AB  - By using a DNA substrate with defined gap size, we found that human
      immunodeficiency virus type 1 reverse transcriptase (HIV-RT) was able to perform
      strand displacement DNA synthesis. This activity was not affected first by calf
      thymus proliferating cell nuclear antigen and replication factor C and second by
      Escherichia coli single-stranded DNA-binding protein, which together allow DNA
      polymerase delta to perform strand displacement DNA synthesis (Podust, V., and
      Hubscher, U. (1993) Nucleic Acids Res. 21, 841-846). 3'-Azido-2',3'
      dideoxythymidine triphosphate inhibited displacement completely, indicating that
      DNA synthesis is required for this reaction. The HIV-RT p66 polypeptide alone
      could perform limited strand displacement DNA synthesis, whereas the HIV-RT p51
      polypeptide was completely inactive, likely due to its inability to replicate
      extensively on a M13 DNA template. On the other hand the HIV-RT p51 polypeptide
      enhanced the strand displacement activity of the HIV-RT p66 subunit at a molar
      ratio of 4:1, mainly by chasing short products into longer ones. Furthermore,
      kinetic experiments after complementation of HIV-RT p66 with HIV-RT p51 indicated
      that HIV-RT p51 can restore rate and extent of strand displacement activity by
      HIV-RT p66 compared with the HIV-RT heterodimer p66/p51, suggesting a function of
      the 51-kDa polypeptide.

PMID- 7507116
TI  - Amylase mRNA transcripts in normal tissues and neoplasms: the implication of
      different expressions of amylase isogenes.
AB  - To understand the cellular origin and mechanism of gene expression in amylase
      producing cancers, the phenotyping of amylase isogenes by the polymerase chain
      reaction and restriction-fragment-length polymorphism using restriction
      endonucleases TaqI, DdeI, HinfI, and AfaI were performed for 3 amylase-producing
      lung adenocarcinomas, 16 lung cancers without hyperamylasemia, other human
      malignant neoplasms, cultured cell lines, and normal tissues. In addition,
      amylase mRNA transcripts were semi-quantified by the limited polymerase chain
      reaction. Amylase mRNA transcripts were detected in all of the tissues examined.
      The AMY1 gene (salivary type) was exclusively and highly expressed in the
      salivary glands and the amylase-producing lung adenocarcinomas. Coexpression of
      the AMY1 gene and AMY2 gene (pancreatic type) was observed in most of the lung
      cancers without hyperamylasemia, lung tissue, and cells scraped from the tracheal
      epithelium, thyroid, and female genital tract (ovary, fallopian tube, and uterus
      cervix), while minimal levels of mRNA transcripts of the AMY2 gene were detected
      in other malignant neoplasms, various normal tissues, and the cultured cell
      lines. All mRNA transcripts identified as being those of the AMY2 gene were
      further identified as being from the AMY2B gene except for the transcripts from
      the pancreas, in which the AMY2A gene and AMY2B gene were coexpressed. On the
      basis of these results, the clinical occurrence of amylase-producing cancer
      likely relates to the tissues expressing the AMY1 gene, while the AMY2B gene,
      which evolutionarily is the oldest gene among human amylase isogenes, is
      constitutively expressed in various tissues.

PMID- 7507117
TI  - Value of serum C-reactive protein measurement in the detection of hepatocellular
      carcinoma superimposed on liver cirrhosis.
AB  - We investigated whether, in Italian patients, C-reactive protein (CRP)
      determination could be considered a useful adjunct, complementary to alpha 1
      fetoprotein, in the detection of liver cancer. CRP was determined by particle
      enhanced nephelometry in 171 subjects (102 male, 69 female). Fifty-five patients
      had mild chronic liver disease (CLD), 45 cirrhosis (CIR), 38 hepatocellular
      carcinoma (HCC); 33 subjects were healthy controls. Patients with HCC and CIR had
      higher CRP levels (P < 0.05) than those found in patients with CLD and controls.
      CRP higher than 5 mg/l was found in 30/38 (78.9%) patients with HCC, 28/45
      (62.2%) patients with CIR, 16/55 (29.1%) patients with CLD (chi 2 56.0, P <
      0.0001). Sensitivity, specificity and diagnostic accuracy of CRP in diagnosing
      HCC with respect to CLD+CIR were: 78.9%, 56.0% and 34.9%. However, when
      considered only in the subgroup of patients with alpha 1-fetoprotein below or
      equalling 30 ng/ml, they were 50.0%, 54.3% and 4.3% respectively. In conclusion,
      CRP concentration is frequently elevated in patients with HCC, however, it does
      not seem to improve the ability of alpha 1-fetoprotein to discriminate HCC from
      CIR.

PMID- 7507118
TI  - Suppressed spontaneous and stimulated growth hormone secretion in patients with
      Cushing's disease before and after surgical cure.
AB  - Growth retardation to complete growth arrest is the hallmark of Cushing's
      syndrome in children. The major mechanism for this has been considered the
      glucocorticoid-induced resistance of target tissues to insulin-like growth factor
      I (IGF-I) and other growth factors. The purpose of this study was to examine the
      GH secretory dynamics of patients with Cushing's disease before and up to 12
      months after their cure by transsphenoidal adenomectomy. In 14 patients, blood
      sampling every 20 min over 24 h for determination of plasma GH was performed
      before and 10-11 days and 3, 6, and 12 months after therapy. These patients also
      underwent arginine infusion and L-dopa stimulation tests and had measurements of
      morning baseline GH-binding protein (GHBP), IGF-I, and IGF-binding protein-3
      (IGFBP-3) plasma concentrations. Fourteen sex- and pubertal stage-matched normal
      volunteers were used as controls. Before therapy, the patient group had an
      increased body mass index (31.5 +/- 5 kg/m2) and markedly decreased plasma mean
      24-h GH concentration, mean peak height, and peak area values, with pulse
      frequency (mean number of peaks) similar to that in the controls. GH values after
      arginine and L-dopa stimulation were also subnormal in many of these patients,
      with 2 of 8 and 8 of 10 failing to show GH responses greater than 7 ng/mL in the
      respective test. In spite of these findings, plasma concentrations of IGF-I,
      IGFBP-3, and GHBP were within the normal range in these patients. Surprisingly, a
      pattern of GH suppression similar to that observed in patients with active
      disease was also seen in patients who were studied 10-11 days and 3, 6, and 12
      months after their cure, when their body mass indexes were progressively
      normalizing, being relatively stable at 10 days, 26.9 +/- 3.8 kg/m2 at 3 months,
      and 24.8 +/- 3.3 kg/m2 at 12 months. In these patients, plasma IGF-I and GHBP
      remained normal, whereas IGFBP-3 decreased significantly, albeit within the
      normal range. The growth rate of 4 patients who were Tanner stage III or below
      and had not completed their growth at the time of the study increased the year
      after surgical cure. These findings suggest that patients with Cushing's disease
      have marked GH suppression during their illness, which, however, does not appear
      to be a major contributor to the growth suppression observed in this condition.
      GH hyposecretion continues for at least a year during convalescence, in spite of
      significant increases in the growth rate in all growing patients.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7507119
TI  - Somatostatin-stimulated insulin-like growth factor binding protein-1 release is
      abolished by hyperinsulinemia.
AB  - It was demonstrated recently that administration of lanreotide and octreotide,
      two somatostatin octapeptide analogs, increased circulating insulin-like growth
      factor binding protein 1 (IGFBP-1) levels. The present study demonstrates that
      native somatostatin 14 shares this ability and that the increase in abolished by
      concomitant hyperinsulinemia within the physiological range. Five fasting healthy
      volunteers underwent a hyperinsulinemic as well as a normo-insulinemic (i.e.
      basal insulinemic) euglycemic clamp lasting 8 h (serum insulin levels remained
      constant, about 570 vs. 16 pmol/L). Immediately before the clamps, a somatostatin
      infusion (500 micrograms/h) was started and continued throughout. During normo
      insulinemia, IGFBP-1 levels increased slowly from 6.3 +/- 6.2 to 36.1 +/- 14.8
      micrograms/L (P < 0.05) reaching maximum after 7 h constant somatostatin
      infusion, whereas hyperinsulinemia induced a significant decrease from basal
      levels (from 4.7 +/- 5.4 to 1.1 +/- 1.5 micrograms/L) after 8 h (mean +/- SD, n =
      5). These results may indicate hitherto unnoticed interactions of somatostatin
      and insulin on IGFBP-1 release with possible impact on IGF-I action at the
      cellular level.

PMID- 7507120
TI  - Dose-dependent stimulation of insulin-like growth factor-binding protein-1 by
      lanreotide, a somatostatin analog.
AB  - It was recently reported that octreotide, besides its many, almost obligatory,
      inhibitory actions, stimulates the release of insulin-like growth factor-binding
      protein-1. The present study sought to exclude the possibility that the
      inescapable preceding somatostatin analog-induced reduction in serum insulin
      participated in the observed effect. We, therefore, administered sc two
      clinically relevant doses (5 and 80 micrograms/kg) of lanreotide, another
      somatostatin octapeptide analog, which induced identical 60% initial suppressions
      of serum insulin. In spite of this, clear dose-dependent increases in insulin
      like growth factor-binding protein-1 were observed, starting between 1-2 h after
      administration of lanreotide, and levels were still elevated several-fold 5 h
      after administration of 80 micrograms/kg lanreotide. In addition, we found that
      infusion of amino acids had no discernible effect on binding protein-1 release.
      The changes found in immunoreactive binding protein-1 were confirmed employing
      Western ligand blotting. The data indicate that the lanreotide-induced increase
      in binding protein-1 levels in serum is not due to the changes in circulating
      insulin. The magnitude and duration of the increase raise the possibility that
      the stimulation may have clinically relevant implications in somatostatin analog
      treatment.

PMID- 7507121
TI  - Partition of insulin-like growth factor (IGF)-binding sites between the IGF-I and
      IGF-II receptors and IGF-binding proteins in the human kidney.
AB  - Quantitative ligand binding autoradiography and in situ hybridization were
      employed to analyze [125I]insulin-like growth factor-I ([125I] IGF-I) and
      [125I]IGF-II-binding sites in human kidney sections. Binding sites for both
      ligands were concentrated in the inner medulla and glomeruli, with low levels
      present in the tubulo-interstitial cortex. Competition with cold IGF-I, IGF-II,
      and insulin was used to determine nonspecific binding and differentiate binding
      of ligands to the IGF-I and IGF-II receptors and IGF-binding proteins (IGFBPs).
      Nonspecific binding was less than 20% of the total for both ligands. Insulin (10(
      5) mol/L), which binds to the IGF-I receptor, but not to the IGF-II receptor or
      IGFBPs, displaced 39 +/- 8% of [125I]IGF-I binding in glomeruli, 60 +/- 7% in the
      tubulo-interstitial cortex, and 32 +/- 7% in the medulla. Insulin produced no
      detectable decrease in [125I]IGF-II binding in any region. IGF-I (10(-8) mol/L),
      which binds strongly to IGFBPs, but not appreciably to the IGF-II receptor,
      produced reductions of 46 +/- 9%, 35 +/- 8%, and 39 +/- 12% in [125I]IGF-II
      binding in glomeruli, tubulo-interstitial cortex, and medulla, respectively. In
      situ hybridization showed that IGFBP-1-5 mRNAs were all expressed in glomeruli.
      IGFBP-2 mRNA was abundant in medullary collecting duct epithelium, whereas IGFBP
      3, -4, and -5 mRNAs were localized in interstitial and vascular cells throughout
      the kidney. IGF-I and -II receptor mRNAs were widely distributed in renal
      epithelium. The abundance of local IGFBP gene expression was positively
      correlated with insulin-nondisplaceable IGF binding in specific kidney regions.
      In summary, [125I]IGF-I binding appears to be partitioned largely to IGFBPs in
      glomeruli and largely to the IGF-I receptor in the tubulo-interstitial cortex,
      with binding in the medulla more evenly divided. The proportion and regional
      distribution of [125I]IGF-II binding to IGFBPs are similar, but the balance
      appears to be primarily associated with the IGF-II, rather than the IGF-I,
      receptor. Finally, this study shows that [125I]IGF binding autoradiography
      combined with in situ hybridization can be used to localize and potentially
      quantitative expression of IGFBPs in tissue sections.

PMID- 7507122
TI  - Intimate contact of chromaffin and cortical cells within the human adrenal gland
      forms the cellular basis for important intraadrenal interactions.
AB  - A new role for the adrenal medulla as a regulator of adrenocortical function has
      been postulated. However, there has been no idea as to how such a cellular
      interaction within the human adrenal gland could take place. In this study we
      were able to demonstrate with the help of specific immunostaining of cortical and
      chromaffin cells, respectively, that the two endocrine systems are interwoven
      with each other to an astonishing degree. Protrusions, clusters, islets, and
      single cortical cells were made visible by immunostaining with an antibody
      against 17 alpha-hydroxylase cytochrome P450 enzyme. They occurred diffusely
      within the entire adrenal medulla, providing ample contact zones for paracrine
      interactions. Specific immunostaining for the neuroendocrine protein chromogranin
      A identified the occurrence of chromaffin cells within all three zones of the
      human adrenal cortex, including the zona glomerulosa. In an ultrastructural
      analysis, cortical and chromaffin cells were found in all zones in direct
      apposition, providing the possibility for direct intercellular exchange. The
      close morphological colocalization of cortical and chromaffin cells revealed in
      this study may constitute the basis for the growing evidence of relevant
      intraadrenal paracrine mechanisms within the human adrenal gland.

PMID- 7507123
TI  - Use of leuprolide acetate response patterns in the early diagnosis of pubertal
      disorders: comparison with the gonadotropin-releasing hormone test.
AB  - The effects of a single injection (500 micrograms sc) of the GnRH agonist
      leuprolide acetate on gonadotropin secretion and those induced by a GnRH test
      were analyzed in 32 children (11 males and 21 females) referred for possible
      pubertal developmental disorders and in 9 prepubertal controls [group C; 4 males
      and 5 females; chronological age (CA), 7.4 +/- 1.2 yr]. The pituitary-gonadal
      secretory responses to the GnRH agonist were characterized in all subjects and in
      a control group in early puberty [10 females (Tanner breast stage II; CA, 11.3 +/
      1.1 yr) and 6 males (Tanner pubertal stage II; CA, 13.5 +/- 0.4 yr); group D].
      Twelve girls (CA, 7.1 +/- 0.7 yr) presented with precocious breast development,
      11 patients [6 boys (CA, 10.9 +/- 0.4 yr) and 5 girls (CA, 9.3 +/- 0.5 yr)] had
      advanced puberty and predicted adult heights below -2.0 SD score, and 9 patients
      [5 boys (CA, 14.6 +/- 0.3 yr) and 4 girls (CA, 14.4 +/- 1.1 yr)] had delayed
      puberty. Less than 6 months had elapsed since the appearance of pubertal signs in
      all patients with pubertal development. After a follow-up period of 12.9 +/- 2.0
      months, 20 patients showed progression of pubertal signs (group A, progressive
      puberty), and in 12, puberty regressed or did not progress (group B,
      nonprogressive puberty). The results of hormonal tests in all patients were
      analyzed retrospectively according to their clinical outcome. Patients in group A
      had a mean plasma peak LH response significantly higher after leuprolide acetate
      stimulation than after GnRH challenge (13.1 +/- 0.2 vs. 7.3 +/- 0.9 IU/L; P <
      0.003). Those in groups B and C had similar peak LH responses after both tests
      (3.3 +/- 0.2 vs. 3.1 +/- 0.4, and 1.5 +/- 0.1 vs. 1.8 +/- 0.4 IU/L,
      respectively). No differences in basal and poststimulated LH levels were found
      between boys and girls in the same group. In patients in groups A and D, LH
      consistently peaked 3 h postleuprolide acetate challenge; in those in groups B
      and C, the LH peak occurred 3-6 h postinjection. Maximal gonadal responses were
      elicited 24 h poststimulation. No overlap in poststimulated estradiol or
      testosterone values occurred between patients in groups A and D and those in
      groups B and C.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7507124
TI  - The biology of the human ligand for CD40.

PMID- 7507125
TI  - B cell activation and human immunodeficiency virus infection. V. Phenotypic and
      functional alterations in CD5+ and CD5- B cell subsets.
AB  - B cell dysregulation is a hallmark of human immunodeficiency virus infection.
      Since B lymphocytes comprise two distinct subpopulations, CD5+ and CD5- cells, we
      addressed their individual phenotypic and functional behavior. Seropositive
      patients with both limited and advanced disease progression had an increased
      percentage of peripheral blood CD5+ B cells, compared to seronegative controls
      (20.1 +/- 2.1 and 22.7 +/- 5.7, respectively, vs 17.0 +/- 3.4 in controls);
      however, due to the lymphopenia and reduced number of circulating B cells in
      infected individuals, the absolute number of CD19+CD5+ lymphocytes was actually
      reduced. Although HIV-specific antibodies were synthesized spontaneously in vitro
      only by CD5- B cells, a 10-fold lower degree of spontaneous, non-HIV-specific
      activation was also displayed by unstimulated CD5+ B cells. These findings
      indicate that B cell dysregulation during HIV infection involves both the CD5-
      and the CD5+ B cell compartments; moreover, in view of the putative role of CD5+
      B cells in autoimmune phenomena and IL-10 production, these data reinforce the
      possibility that B cell dysfunction might be causally involved in AIDS
      pathogenesis.

PMID- 7507126
TI  - Circulating cytotoxic immune components in dominant Charcot-Marie-Tooth syndrome.
AB  - Activated T cells, measured repeatedly in the demyelinating peripheral
      neuropathy, Charcot-Marie-Tooth syndrome (CMT; hereditary motor sensory
      neuropathy), might participate in myelin loss by a destructive inflammatory
      autoimmune process. To explore this possibility, plasma proportions of
      hydroxyleukotrienes, their fatty acid precursor, arachidonic acid, and lymphocyte
      epitopes associated with immune cell activation expression were measured in 18
      adults with dominant, Type I CMT. Compared to age-matched normal controls, CMT I
      patients showed eicosanoid-linked immunoactivation by an elevated content of 12
      hydroxy-eicosatetraenoic acid (12-HETE) in parallel with a decreased plasma
      percentage of its fatty acid precursor, arachidonic acid. CMT patients also had
      increased numbers of peripheral lymphocytes expressing activation-related
      epitopes, CD25+, CD26+, CD4+, and CD4/CD45RO+ primed memory cells, with enhanced
      CD8+ cytotoxic cells and soluble CD8 protein content. Therefore, endogenously
      stimulated CMT I lymphocytes include functional cytotoxic cells which appear to
      deplete the plasma fatty acid precursor of prostenoid agents during the secretion
      of potentially destructive cytokines.

PMID- 7507127
TI  - Suppression of antibody responses to ricin A chain (RTA) by monoclonal anti-RTA
      antibodies.
AB  - Balb/c mice treated with an immunotoxin constructed by conjugation of murine
      monoclonal antibody 791T/36 via a disulfide linker to ricin A chain generate a
      pronounced antibody response to peptide epitopes on ricin A chain. Monoclonal
      anti-RTA antibodies which recognize peptide epitopes have been developed and
      these have been used to down-regulate anti-RTA antibody responses in 791T/36-RTA
      immunotoxin-treated Balb/c mice. Of the five MAB tests, two (608/7 and 596/134)
      proved most effective, inhibiting anti-RTA antibody formation by up to 73%. MAB
      treatment was effective when initiated up to 3 days after immunotoxin treatment.
      Pharmacokinetic studies with 791T/36-RTA have shown that the immunotoxin is
      rapidly eliminated from the circulation, with no more than 4% remaining in blood
      after 24 hr. It is proposed that the down-regulation of anti-RTA antibodies is
      effected by MAB interfering with antigen processing.

PMID- 7507128
TI  - Insulin-like growth factor (IGF), IGF binding protein (IGFBP), and IGF receptor
      gene expression and IGFBP synthesis in human uterine leiomyomata.
AB  - Oestradiol is important in the growth of uterine leiomyomata and may act
      primarily or secondarily through mediators such as growth factors, including the
      insulin-like growth factors (IGF-I and IGF-II), mitogenic peptides. IGF binding
      proteins (IGFBPs) modulate IGF actions at their target cells. The objective of
      this study was to examine the possible steroid dependence of IGF, IGFBP and IGF
      receptor gene expression and IGFBP synthesis in uterine leiomyomata, using
      tissues from women cycling normally and made hypo-oestrogenic by a gonadtrophin
      releasing hormone agonist (GnRHa). Using a solution hybridization ribonuclease
      protection assay, anti-sense RNA probes for IGF-I, IGF-II and beta-actin
      (control) were hybridized with total RNA isolated from leiomyomata exposed in
      vivo to a range of serum oestradiol (< 40-240 pg/ml) and progesterone (0-10
      ng/ml) concentrations. IGF-I gene expression was most abundant in leiomyomata
      obtained during the late proliferative phase of the cycle and was undetectable in
      leiomyomata from hypo-oestrogenic patients. IGF-II gene expression was not
      dependent on endogenous steroid concentrations or cycle stage. IGFBP gene
      expression was investigated by Northern blotting. The order of relative abundance
      of IGFBP mRNAs was IGFBP-4 >>> IGFBP-3 >> IGFBP-5 > IGFBP-2 and was not dependent
      on the in-vivo oestrogen status. Type I and type II IGF receptor gene expression
      was investigated by polymerase chain reaction using gene-specific primers. Type I
      and type II IGF receptor mRNAs were detected in leiomyomata and were not
      dependent on cycle stage or in-vivo oestrogen status. Explant cultures of
      leiomyomata and myometrium synthesized IGFBP-3 (mol. wt = 38-43 kDa), IGFBP-4,
      and binding proteins of mol. wt = 34 and 31 kDa. Identification of IGFBP-2 was
      inconclusive, and IGFBP-1 was not detected. These data support the hypothesis
      that IGF-I, but not IGF-II, may be a mediator of oestradiol action in the growth
      of uterine leiomyomata, and that IGFBPs may further modulate, by an autocrine or
      paracrine mechanism, IGF-I action in this tissue.

PMID- 7507129
TI  - Failed oocyte retrieval in in-vitro fertilization with documented positive serum
      beta-human chorionic gonadotrophin (HCG) concentration on day HCG+1.
AB  - No oocytes were obtained at ovum retrieval in a 33-year-old patient with
      secondary tubal infertility, whereas in a previous cycle nine oocytes were
      obtained under the same ovarian stimulation protocol as used in the studied
      cycle. Oocyte retrieval failed in spite of the correct administration of human
      chorionic gonadotrophin (HCG) as demonstrated by serum beta-HCG concentration
      (58.6 mIU/ml) on day HCG+1. However, it was shown that progesterone failed to
      rise even after the administration of exogenous HCG as the luteinizing hormone
      signal. Therefore, when ovum retrieval fails, the serum progesterone as well as
      beta-HCG concentrations may be useful to help identify the cause of this unusual
      event.

PMID- 7507130
TI  - Evidence of beta 1 integrins and fibronectin on spermatogenic cells in human
      testis.
AB  - Interactions between human spermatozoa and oocytes are an essential event in the
      process of fertilization. Cell-cell and cell-matrix interactions in somatic cells
      are mediated by adhesion molecules such as beta 1 integrins (very late antigens;
      VLA). Therefore, we investigated the expression of beta 1 integrins and the
      matrix proteins collagen IV, fibronectin and laminin in human testis by
      immunohistology. Monoclonal antibodies against the beta chain of beta 1 integrins
      reacted with the basement membrane of the tubuli seminiferi, spermatocytes,
      spermatids and testicular spermatozoa. The alpha 3, -5 and -6 chains of beta 1
      integrins showed the same pattern, whereas, the alpha 1, -2 and -4 chains could
      not be detected on spermatogenic cells. These VLA subunits were localized on
      endothelial cells, leukocytes and basement membranes. Matrix proteins such as
      laminin, collagen IV and fibronectin were detectable as components of basement
      membranes in human testis. Germinal cells except spermatogonia expressed
      fibronectin only. These results demonstrate that beta 1 integrins and matrix
      proteins in human testis are normally expressed on somatic tissue and that
      germinal cells, especially spermatocytes, spermatids and spermatozoa show
      positive reactions with antibodies against the VLA-3, -5 and -6 complexes and
      fibronectin. These findings suggest a production of beta 1 integrins and
      fibronectin during the spermatogenesis and a role of these proteins in adhesive
      mechanisms of spermatozoa similar to somatic cell-cell or cell-matrix
      interactions.

PMID- 7507131
TI  - Use of fetal bovine serum substitutes for the protection of the mouse zona
      pellucida against hardening during cryoprotectant addition.
AB  - The addition of 20% fetal bovine serum (FBS) to media used for mouse oocyte
      cryopreservation prevents hardening of the zona pellucida that otherwise can
      occur due to premature release of cortical granule contents (George et al., Hum.
      Reprod., 7, 401-412, 1992). Protection of human oocytes would ideally be achieved
      by using a human macromolecular source or a more defined bovine source than total
      FBS. Here we investigate whether FBS can be replaced by human serum, human cord
      serum, human serum albumin or fetuin, the major protein component of FBS. Only
      fetuin was found to be effective.

PMID- 7507132
TI  - Reduced circulating placental protein concentrations during the first trimester
      are associated with preterm labour and low birth weight.
AB  - Serum concentrations of human chorionic gonadotrophin (HCG),
      Schwangerschaftsprotein 1 (SP-1), pregnancy-associated plasma protein A (PAPP-A),
      progesterone and oestradiol were measured at weekly intervals between the fifth
      (embryo transfer plus 3 weeks) and 13th week of gestation during the first
      trimester of pregnancies achieved following in-vitro fertilization (IVF) and
      embryo transfer in a group of women who delivered before (n = 8) or at term (n =
      52). Those women who had a preterm delivery had significantly lower
      concentrations of PAPP-A (weeks 7-13; P = 0.0001-0.028) and SP-1 (weeks 6-8 and
      10-12; P = 0.004-0.04). After correction of birth weight for sex and gestational
      age at delivery, preterm delivery was found not to be associated with growth
      retardation. However, comparison of the circulating concentrations of the
      substances analysed in mothers who delivered babies of < 85% of the 50th centile
      of the normal range of birth weight for a given gestational age and sex, with
      those who delivered babies of > 85% revealed that the concentrations of HCG (P =
      0.012-0.04 on weeks 6-9) and SP-1 (P = 0.003-0.03 on weeks 7, 9-13) were
      significantly lower in the former group. Weak, inconsistent associations were
      found between the circulating concentrations of HCG, SP-1 and PAPP-A and both
      corrected birth weight and gestational age at delivery. Thus, both the
      gestational age at delivery and low birth weight may be related to impaired
      placental development/function during the first trimester.

PMID- 7507134
TI  - Cellular adhesion antigen modulation in purpura pigmentosa chronica.
AB  - BACKGROUND: Purpura pigmentosa chronica is an inflammatory skin disorder probably
      caused by an allergic reaction. Delayed-type hypersensitivity or immunocomplex
      vasculitis has been considered as a possible mechanism. OBJECTIVE: Detailed
      analysis of cell adhesion molecule (CAM) modulation may give further insights
      into the pathogenesis and underlying immune reaction of this disease. METHODS: By
      immunohistochemical techniques we investigated the in situ expression of
      integrins, selectins, and CAMs of the immunoglobulin superfamily. RESULTS:
      Infiltrating lymphocytes expressed LFA-1, LFA-2, VLA-4, and VLA-5, whereas some
      of the macrophages were also positive for p150/95 and MAC-1. VLA-1 was found on
      lymphocytes near the basement membrane of the epidermis. Compared with uninvolved
      or healthy skin endothelial cells showed upregulation of ICAM-1, VCAM-1, and,
      focally, E-selectin. Some fibroblasts were positive for ICAM-1. ICAM-1 was also
      upregulated on lesional keratinocytes that also expressed alpha 2, alpha 3, and
      alpha 6 integrin chains on basal and suprabasal epidermal layers. CONCLUSION: Our
      findings demonstrate characteristic modifications in the expression of CAMs in
      purpura pigmentosa chronica and indicate the involvement of the epidermis in this
      disease. This modulation shows close parallels to those described for chronic
      delayed-type immune reactions of the skin.

PMID- 7507133
TI  - The expression of c-kit protein in human adult and fetal tissues.
AB  - The c-kit proto-oncogene encodes a tyrosine kinase receptor and is allelic with
      the dominant white-spotting (W) locus of the mouse. In this study we investigated
      the expression of human c-kit protein in various adult and fetal human tissues
      immunohistochemically using anti-human c-kit monoclonal antibody. To discriminate
      c-kit+ cells from mast cells expressing c-kit, mast cells were identified by
      staining with Toluidine blue. In oogonia, spermatogonia and skin melanocytes of
      the fetus and in oocytes of adult ovary, c-kit expression was detected. In adult
      uterus, c-kit+ cells were widely distributed in the basal layer of the
      endometrium, myometrium and cervix, the number and distribution being almost
      identical to those of mast cells. In fetal uterus, c-kit+ non-mast cells
      clustered beneath the epithelium and a few mast cells were observed in the
      myometrium and subserosal layer. In both adult and fetus, c-kit+ non-mast cells
      were detected within smooth muscle layers of the intestine, colon and oesophagus,
      while mast cells were observed in the mucosal and submucosal layers of these
      organs. In contrast to mice, no expression of c-kit protein was detected in the
      human placenta and decidua. Thus, the distribution of c-kit+ cells in various
      tissues is similar but not identical between adult and fetus and between human
      and mouse.

PMID- 7507135
TI  - Treatment of aquagenic pruritus with topical capsaicin cream.
AB  - BACKGROUND: Aquagenic pruritus is characterized by pruritus after contact with
      water; there are no objective cutaneous changes. Capsaicin, which induces the
      release of neuropeptides from A delta and C cutaneous nerve fibers, has been
      successfully used in the treatment of several dermatoses associated with
      pruritus. Among the many different neuropeptides present in human skin, the
      undecapeptide substance P has been shown to cause pruritus. OBJECTIVE: We
      evaluated the clinical effect and searched for alterations in cutaneous
      neuropeptidergic fibers before and after treatment with capsaicin cream. METHODS:
      Five patients with aquagenic pruritus were treated with capsaicin cream 0.025%,
      0.5% or 1.0% three times daily for 4 weeks. Direct immunofluorescence (DIF) was
      performed before and after treatment to evaluate the storage of neuropeptides in
      the A delta and C type cutaneous nerve fibers. RESULTS: Before treatment (when by
      DIF the neuropeptidergic fibers appeared filled with neuropeptides), contact with
      water consistently provoked itching. After capsaicin treatment (when by DIF the
      neuropeptidergic fibers were depleted of neuropeptides), contact with water did
      not evoke pruritus. Areas of skin treated with the vehicle alone showed no
      clinical improvement or change in neuropeptide content. CONCLUSION: This study
      suggests that neuropeptides, including substance P, may contribute to mediating
      the itch in aquagenic pruritus.

PMID- 7507136
TI  - Palliative care in the acute hospital setting.

PMID- 7507137
TI  - Echinostoma caproni and E. trivolvis alter the binding of glycoconjugates in the
      intestinal mucosa of C3H mice as determined by lectin histochemistry.
AB  - Mouse (C3H) mucosal glycoconjugates were examined in normal small intestines and
      intestines infected with Echinostoma caproni or E. trivolvis using six different
      fluorescein-conjugated lectins: Triticum vulgaris agglutinin (WGA), Ulex
      europaeus agglutinin I (UEA-I), Ricinus communis agglutinin I (RCA-I), Glycine
      max soybean agglutinin (SBA), Dolichos biflorus agglutinin (DBA), and Arachis
      hypogaea peanut agglutinin (PNA). The expression of lectin-binding sites and the
      intensity of the binding of lectins in the mouse small intestines were changed by
      infection with the echinostomes. Specific differences in the reaction to
      glycoproteins were clearly observed between the mouse intestines infected with E.
      caproni and those infected with E. trivolvis. In E. caproni infection, binding of
      most of the lectins to the villi was remarkably reduced in accord with the
      villous atrophy and loss of goblet cells. In contrast, in E. trivolvis infection,
      the binding of WGA, RCA-I and DBA was reduced in the microvillar surfaces, but
      binding of UEA-I and SBA were unchanged compared to the control intestines. The
      lectin binding to goblet cells in E. trivolvis-infected mice mostly increased.
      These observations may reflect the marked increase in goblet cells and the less
      severe damage in the villi of E. trivolvis infection compared to E. caproni
      infection. Most of the glycoconjugates were slightly reduced in the hyperplastic
      crypts except for N-acetyl glucosamine. It is possible that glucose metabolism in
      the host intestines infected with E. trivolvis was activated, resulting in an
      increase in the rate of mucin synthesis as well as qualitative changes in mucus,
      thereby mediating the expulsion of the worms.

PMID- 7507138
TI  - Cytochemical observations on the nervous system of adult Corrigia vitta.
AB  - Adult Corrigia vitta (Trematoda: Dicrocoelidea) inhabit the pancreatic duct of
      the fieldmouse, Apodemus sylvaticus, where, in numbers, they may occlude the duct
      lumen and prevent the flow of pancreatic secretions. Enzyme histochemical and
      immunocytochemical techniques, in conjunction with confocal scanning laser
      microscopy, have been used to examine the localization and distribution of
      cholinergic, serotoninergic (5-HT, serotonin) and peptidergic components of the
      nervous system of the adult worm. All three classes of neuronal mediator showed a
      common pattern of staining, occurring throughout the central and peripheral
      nervous systems. Of the four peptide immunoreactivities (IR) demonstrated
      (pancreatic polypeptide (PP), peptide YY (PYY), substance P (SP), FMRFamide), PP
      IR was the most predominant, occurring not only within the central ganglia and
      longitudinal nerve cords, but also in subtegumental plexuses and in fibres
      associated with the egg-forming apparatus. PYY and FMRFamide IRs were evident
      throughout the central and peripheral nervous systems; FMRFamide immunostaining,
      in particular, highlighted innervation of the ootype and immunoreactive cell
      bodies around the Mehlis' gland. Both SP- and 5-HT-IRs were restricted to the
      cerebral ganglia, ventral nerve cords and associated cell bodies. The
      distribution patterns of these peptides and 5-HT within the nervous system of C.
      vitta suggest they are likely to function as neuronal mediators. PP, PYY and
      FMRFamide may also serve in regulating egg production.

PMID- 7507139
TI  - Some ascites monoclonal antibody preparations contain contaminants that bind to
      selected Golgi zones or mast cells.
AB  - A small proportion of mouse ascites fluid induced by hybridomas producing
      monoclonal antibodies or myelomas secreting immunoglobulin yielded staining that
      was confined to the Golgi zone of certain epithelial cell types in rats and
      gerbils but not in mice. In addition, a commercial IgG fraction from mouse plasma
      similarly labeled the Golgi area, unlike IgG from mouse serum from another
      source. Culture supernatant from one hybridoma line contrasted with ascites fluid
      produced by the same hybridoma in failing to stain the Golgi region. The capacity
      of a fluid to react with the Golgi cisternae bore no relationship to the class of
      immunoglobulin secreted by the hybridoma or myeloma. Absorption of an ascites
      fluid with blood group A1 human erythrocytes eliminated its affinity for Golgi
      cisternae. Adsorption with blood group A2 or B or two type O cells used for
      screening for blood group antibodies had no effect on Golgi zone labeling by this
      ascites fluid. The positive cells included most serous secretory cells in rats,
      serous cells of sublingual and tracheal glands, and some endometrial and oviduct
      lining cells in gerbils, and columnar lining cells of small intestine and cecum
      and all or part of the lining cells in some prostate lobes in both genera. Some
      of the tested ascites fluids stained mast cells. The agent accounting for mast
      cell labeling differed, however, from that reacting with Golgi cisternae in its
      distribution among the mouse ascites fluids examined, lack of relationship to the
      ABO blood group system, occurrence additionally in normal rat serum, and capacity
      to stain cells in mice as well as rats and gerbils.

PMID- 7507140
TI  - A method for identifying peripheral connections of perivascular nerves based on
      sensitive acetylcholinesterase staining via perfusion.
AB  - To identify peripheral connections of perivascular nerves, which are usually hard
      to find and easily damaged, we developed a sensitive method for
      acetylcholinesterase (AChE) staining in rat. The procedure is based on primary
      staining via perfusion, which permits visualization of perivascular nerves before
      dissection and, after dissection, further staining via immersion for
      identification of peripheral connections of the earlier stained perivascular
      nerves. The AChE histochemistry is based on an intensification method originally
      described for sections. The procedure has been optimized for staining via
      vascular perfusion and can also be applied on whole-mount preparations via
      immersion. The results show intense nerve staining with minimal background.
      Although the procedure was initially developed for cerebrovascular nerves, the
      staining approach can also be applied in other regions, the main advantage being
      that perivascular neural structures can be identified without the damage that
      usually occurs during dissection.

PMID- 7507141
TI  - Demonstration of acidity in intestinal vacuoles of the suckling rat and pig.
AB  - Fluorescence staining characteristics of "large vacuoles," i.e. vacuoles ranging
      up to almost cell size, were studied in suckling rats and pigs. In the distal
      epithelium of the small intestine of suckling rat, yellow autofluorescence and
      accumulation of orally administered FITC-dextran were observed in the
      supranuclear vacuole. In both species the weakly basic amino dye acridine orange
      (AO) stained the nuclei at neutral pH bright yellow-green and the transport and
      digestive vacuoles bright red or orange. It is concluded that trapping and
      accumulation of the dye (red shift) were due to the acidity of the vacuolar
      interior. Assessment of the vacuolar pH in rat enterocytes is in agreement with
      published data on lysosomal pH values. Acidic buffers, lysosomotropic and
      destructive agents, or illumination with bright light induced irreversible fading
      of AO-stained vacuoles; the color of the porcine transport vacuoles was the most
      labile. This fading was used to differentiate vacuoles from other structures,
      e.g., vacuolar inclusion bodies and goblet cells. In suckling rat, staining
      characteristics of the gut epithelium changed on Days 19 and 20 of postnatal age.
      Detection of acidity in the distal (digestive) vacuoles supports the lysosome
      like nature of their function. They appear to constitute an auxiliary,
      intracellular digestive system for the young animal. However, the function of
      acidity in the non-digestive transport vacuoles of newborn pig is unclear.

PMID- 7507142
TI  - Widespread expression of perlecan proteoglycan in basement membranes and
      extracellular matrices of human tissues as detected by a novel monoclonal
      antibody against domain III and by in situ hybridization.
AB  - Perlecan, a multidomain heparan sulfate proteoglycan (PG), is an intrinsic
      component of basement membranes and extracellular matrices. We used a prokaryotic
      expression vector to generate fusion proteins encoding various domains of human
      perlecan protein core and these recombinant proteins were used as immunogens to
      produce mouse anti-human monoclonal antibodies (MAb). One MAb, designated 7B5,
      was characterized by Western blotting and ELISA and was shown to react
      specifically with the laminin-like region of perlecan (Domain III) but not with
      two other fusion proteins encoding Domain II or V. This perlecan epitope was
      detected by immunoenzymatic staining in the basement membranes of human tissues
      including pituitary gland, skin, breast, thymus, prostate, colon, liver,
      pancreas, spleen, heart, and lung. All vascular basement membranes tested
      contained this gene product. In addition, sinusoidal vessels of liver, spleen,
      lymph nodes, and pituitary gland expressed high levels of perlecan in the
      subendothelial region. In situ hybridization, using as probe the same human cDNA
      encoding Domain III, localized perlecan mRNA to specific cell types within the
      tissues and demonstrated that in skin, perlecan appears to be synthesized
      exclusively by connective tissue cells in the dermal layer. The availability of
      MAb against precise regions of human perlecan will allow the investigation of
      this gene product in normal and diseased states.

PMID- 7507143
TI  - Charcot-Leyden crystal protein distribution in basophils and its absence in mast
      cells that differentiate from human umbilical cord blood precursor cells cultured
      in murine fibroblast culture supernatants or in recombinant human c-kit ligand.
AB  - Suspension cultures of human umbilical cord blood mononuclear cells supplemented
      with c-kit ligand-containing additives give rise to a mixture of cells belonging
      to several lineages. Among those that differentiate in quantity are mature
      basophils, immature mast cells, and neutrophilic myelocytes. We used an
      ultrastructural immunogold method to detect the Charcot-Leyden crystal (CLC)
      protein, an eosinophil- and basophil-specific protein, to study cells that were
      obtained at sequential times from 3 to 14 weeks in culture. Basophils (and
      eosinophils, which were present in smaller numbers) labeled for the CLC protein;
      mast cells did not. The labeled basophil subcellular sites included formed
      intragranular, cytoplasmic and nuclear CLCs, cytoplasmic particle-filled and
      homogeneously dense granules, cytoplasm, nucleus, plasma membrane, and
      cytoplasmic and Golgi area vesicles. Individual basophil ultrastructural
      phenotypes similar to those associated with stimulated release and recovery
      reactions showed the expected variations in the gold-labeled subcellular
      compartments. Macrophages also were labeled for CLC protein within endocytotic
      lysosomal structures; neutrophilic myelocytes did not contain CLC protein. On the
      basis of findings reported here, the combined ultrastructural morphology and
      immunogold phenotyping of cells differentiating in c-kit ligand-supplemented
      cultures allows accurate lineage assignment of the developing cells.

PMID- 7507144
TI  - Multiparameter analysis of primary epithelial cultures grown on cyclopore
      membranes.
AB  - The use of porous membranes as culture support for epithelial cells has
      previously been shown to cause functional differentiation of these cells
      mimicking an in vivo condition, in contrast to culture on plastic. The different
      materials of which the membranes are made also have different properties, such as
      transparency, rigidity, and retention of molecules. Cyclopore membranes
      (polyethylene terephtalate) are permeable, transparent, rigid, and have low
      protein retention. In this study we examined the applicability of assessing
      multiple parameters on a single culture of primary epithelial cells on a
      Cyclopore membrane. Cultures of transitional epithelial cells on these membranes
      differentiate into an organoid-like epithelium. We were able to perform
      morphometric analysis during and after cell culture and to quantitate
      proliferation and differentiation by double immunoenzymatic staining. On these
      cultures, quantitative radiochemical analysis could also be achieved, retaining
      the morphology and the immunohistochemical staining. Cross-sections of paraffin
      embedded and plastic-embedded cultures were analyzed qualitatively by light and
      transmission electron microscopy, respectively. Finally, cytokeratins in these
      cultures could also be visualized by immunofluorescence analysis. This
      suitability for simultaneous assessment of both qualitative and quantitative
      parameters on a single cell culture grown on a Cyclopore membrane reduces the
      need of biological materials and may lead to better insight into physiological
      processes.

PMID- 7507145
TI  - In vitro immunization of mouse spleen cells for the production of monoclonal IgG1
      antibodies using an antigen-specific T helper cell clone (D.10.G4.1).
AB  - The in vitro immunization of mouse spleen cells for the production of antigen
      specific monoclonal antibodies has been investigated in detail. Using various,
      previous published in vitro immunization protocols with and without antigen, we
      were able to show that IgM antibody production was not induced by the antigen.
      Nevertheless we developed a new in vitro immunization protocol for eliciting
      antigen-specific monoclonal IgG1 antibodies. Specific antibodies were generated
      by an antigen-driven immune response which included an immunoglobulin class
      switch. Co-culture of mouse spleen cells with an activated conalbumin specific T
      helper cell clone (TH2 D.10.G4.1) in the presence of conalbumin elicited three
      monoclonal IgG1 antibodies that bound specifically to conalbumin. We conclude
      that for the in vitro generation of monoclonal antibodies against T cell
      dependent proteins the addition of antigen activated specific TH2 cell clones is
      essential.

PMID- 7507146
TI  - Evidence of surface antigen detachment during incubation of cells with
      immunomagnetic beads.
AB  - We have studied the attachment of immunomagnetic beads to different cells, with
      particular interest in cells that did not, as expected, appear to bind antibody
      coated beads. Through the use of immunofluorescence and laser scanning confocal
      microscopy it was possible to demonstrate that beads can detach significant
      amounts of antigen from the surface of cells. This results in the appearance of
      antigen-depleted yet viable cells. Moreover, the detached antigen is found to be
      bound to beads and is associated with fragments of cell membrane which can also
      carry other (non-bead binding) cell surface proteins. After reculturing, antigen
      depleted cells can recover their normal levels of surface antigen. Our results
      demonstrate the existence of an immunobead-induced cell membrane detachment
      phenomenon that can lead to the removal of all of a specific surface antigen
      without killing the cells, as judged by both vital staining and reculturing. An
      important aspect of this phenomenon is that immunoidentification of immunobead
      selected populations of cells will give erroneous results. This may thus be of
      significance for the immunobead-based cell depletion methods that are used in
      medicine.

PMID- 7507147
TI  - A vector driving the expression of foreign cDNAs in the MHC class II-positive
      cells of transgenic mice.
AB  - We describe a plasmid vector that drives the expression of foreign cDNAs in
      transgenic mice, according to the dictates of an MHC class II gene promoter.
      Using this vector, we have often obtained mRNA and protein synthesis with a
      tissue and cell-type specificity indistinguishable from that of the endogenous
      MHC class II genes.

PMID- 7507148
TI  - The effect of alpha 2 macroglobulin in commercial cytokine assays.
AB  - alpha 2 macroglobulin (alpha 2M), a 725 kDa plasma protein, has been reported to
      bind a range of cytokines. We have therefore investigated its effect on a number
      of commercial cytokine assays. The methylamine converted fast form of the
      molecule was found to reproducibly depress, by 26% or more, the standard curves
      obtained with certain commercial assays for IL-2 and for tumor necrosis factor
      alpha, and had a small inhibitory effect on some IL-4 assays. In contrast it
      slightly enhanced or had no effect on ELISAs for IL-1 beta and IL-6. The
      inhibition observed was directly proportional to the concentration of alpha 2 M
      used in the range 0.5-5 mg/ml. Studies in the IL-2 system also revealed that it
      was largely attributable to the fast form of alpha 2M. Preliminary evidence
      suggests that the effects observed may be dependent on the assay source. These
      findings may be relevant to the assay of biological fluids in which alpha 2 M is
      present.

PMID- 7507149
TI  - Monoclonal antibodies as probes to detect conformational changes in the rat
      cysteine proteinase inhibitor cystatin A.
AB  - Five monoclonal antibodies (MAbs), 77, 114, 138, 175 and 187, were established
      for rat cystatin A. MAbs 77, 114, 138 and 175 were shown to belong to the IgG1
      subclass, whereas MAb 187 was an IgM. These MAbs partially suppressed inhibitory
      activity of rat cystatin A to papain. Their epitopes were mapped in detail on the
      molecule by examining the reactivities of the MAbs with NH2-terminally truncated
      forms and fragments of rat cystatin A by an enzyme-linked immunosorbent assay
      (ELISA), and by reactivity with the inhibitor on immunoblotting. In competitive
      binding assays the MAbs did not compete with each other, indicating that the
      epitopes recognized by these MAbs were substantially different. The
      conformational epitope recognized by the three MAbs 114, 138 and 175 belonged to
      one group that was highly sensitive to denaturation, but those epitopes were
      unchanged by NH2-terminal truncation. MAb 187 was able to recognize a linear
      epitope present in amino acid residues 15-50 in the NH2-terminal region. MAbs 77
      and 114 reacted weakly with mouse cystatin A but not at all with human cystatin
      A, whereas MAb 187 reacted similarly with mouse cystatin A but at about half that
      level with human. The MAbs produced in this study should be useful tools for
      detecting conformational changes in the rat cystatin A molecule.

PMID- 7507151
TI  - Mutations in the H1 and 1A domains in the keratin 1 gene in epidermolytic
      hyperkeratosis.
AB  - In the autosomal dominant disorder epidermolytic hyperkeratosis, the structural
      integrity of the keratin intermediate filaments is altered in the suprabasal
      layers of the epidermis. We and others have used genetic linkage studies and
      mutation analysis to establish that single amino acid substitutions in either the
      keratin 1 or keratin 10 chains can cause epidermolytic hyperkeratosis. However, a
      larger database of mutations is required to better understand the relationship
      between specific mutations in these keratin chains and their effect on keratin
      filament structure. A larger database will also provide a catalog that may be
      useful for genetic counseling purposes. In this paper, we report the
      identification of three new mutations of the keratin 1 chain of epidermolytic
      hyperkeratosis probands in highly conserved residues in the H1 or beginning of
      the 1A rod domain segments. These correspond to regions involved in molecular
      overlaps between neighboring molecules in keratin filaments. Using an in vitro
      assay, synthetic peptides bearing these substitutions show diminished capacity to
      disassemble preformed filaments in vitro in comparison to the wild type peptides.
      Moreover, analyses of all mutations in epidermolytic hyperkeratosis known to date
      demonstrate remarkable clustering in the molecular overlap region. We conclude
      that non-conservative substitutions in the overlap region are likely to interfere
      with normal keratin filament structure and function, leading to pathology.

PMID- 7507150
TI  - Prenatal diagnosis of epidermolytic hyperkeratosis by direct gene sequencing.
AB  - Epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma) is
      an autosomal dominant skin disorder caused by defects in the suprabasal keratins.
      Recently, mutations in the keratins 1 and 10 have been identified in patients
      with this disease. In this study, direct gene sequencing was used to establish
      the prenatal diagnosis in 15-week gestation twins at risk for epidermolytic
      hyperkeratosis. Direct sequence analysis of genomic DNA from the affected father
      and from both chorionic villus samples revealed a tyrosine to asparagine mutation
      at position 14 within the highly conserved 1A alpha-helical segment of keratin
      10. None of the unaffected family members that were analyzed exhibit this
      mutation nor have polymorphic variations been observed in the normal population
      at this position. This residue is invariant in all type I keratins sequenced to
      date and is also conserved in related intermediate filament proteins such as
      vimentin and lamin. Given this high degree of conservation it is probable that
      any mutation at this position is deleterious and will result in disease.

PMID- 7507152
TI  - Mutations in the rod 1A domain of keratins 1 and 10 in bullous congenital
      ichthyosiform erythroderma (BCIE).
AB  - Bullous congenital ichthyosiform erythroderma is a human hereditary skin disorder
      in which suprabasal keratinocytes rupture. Recent reports have implicated
      keratins K1 and K10 in this disease. Here we describe four diverse keratin
      mutations that are all significantly associated with this disease. Two of these
      are in the helix 1A subdomain of the type II keratin 1, giving a serine-to
      proline substitution in codon 185 and an asparagine-to-serine substitution in
      codon 187. In the analogous region of type I keratin 10, an arginine-to-proline
      and an arginine-to-serine transition in codon 156 have been identified. All four
      mutations create restriction fragment length polymorphisms that were used exclude
      the mutations from 120 normal chromosomes. Insertional polymorphism (in the V2
      subdomains of the non-helical tails of K1 and K10) was excluded as the cause of
      the phenotypic heterogeneity observed within one family.

PMID- 7507153
TI  - Biologic activities of retinoic acid and 3,4-didehydroretinoic acid in human
      keratinocytes are similar and correlate with receptor affinities and
      transactivation properties.
AB  - The biologic activities of retinoic acid and 3,4-didehydroretinoic acid, two
      endogenous vitamin A derivatives in various tissues, were compared to their
      affinities for the nuclear retinoic acid receptors and their ability to induce
      transcriptional activation. Both retinoids were equipotent inducers of
      differentiation of F9 teratocarcinoma cells. In a morphologic assay, using
      reconstructed skin, retinoic acid and 3,4-didehydroretinoic acid inhibited
      keratinization at a concentration of 100 nM. In cultured keratinocytes, a 50%
      inhibition of the production of the keratinocyte transglutaminase enzyme was
      achieved with about 20 nM for both retinoids. The in vitro binding to the nuclear
      retinoic acid receptors alpha, beta, and gamma showed that retinoic acid and 3,4
      didehydroretinoic acid had almost equal affinities for the receptors with Kds
      ranging from 3 to 47 nM. The transcriptional activation resulting from the
      addition of the two retinoids to cells co-transfected with alpha, beta, or gamma
      retinoic acid receptor expression vectors and a retinoic acid responsive element
      linked to the chloramphenicol acetyltransferase reporter gene was similar.
      Finally, it was demonstrated that retinoic acid did not metabolize to 3,4
      didehydroretinoic acid, and a slow conversion of 3,4-didehydroretinoic acid into
      retinoic acid was not sufficient to explain the biologic effects produced by the
      former compound. In conclusion, the present study demonstrates that retinoic acid
      and 3,4-didehydroretinoic acid have the same activity in several different test
      systems, but their metabolism differs depending on the cell type used.

PMID- 7507154
TI  - Non-sensitizing epicutaneous skin tests prevent subsequent induction of immune
      tolerance.
AB  - Oral administration of nickel or chromium to naive guinea pigs results in immune
      unresponsiveness to subsequent induction of allergic contact hypersensitivity.
      Such "oral tolerance" depends on the oral dose, is antigen specific, T-suppressor
      cell mediated, and very persistent. In contrast, oral antigen administration to
      sensitized animals results at best in transient desensitization. Here we report
      that even non-sensitizing epicutaneous skin contacts prevented the subsequent
      induction of oral tolerance. These data support the view that primed T cells are
      less sensitive to suppressor T-cell function than naive T cells.

PMID- 7507155
TI  - Differential inhibition of cutaneous T-cell-mediated reactions and epidermal cell
      proliferation by cyclosporin A, FK-506, and rapamycin.
AB  - Although cyclosporin A is a highly effective treatment for several skin
      disorders, particularly psoriasis, its use in dermatology appears limited due to
      drug-induced hypertension and nephrotoxicity. Newer, similar-acting anti-T-cell
      agents such as FK-506 and rapamycin may be more effective; therefore a comparison
      was made with cyclosporin A to assess their inhibitory action on T-cell responses
      and keratinocyte proliferation. Using a guinea-pig model of delayed-type
      hypersensitivity to dinitrofluorobenzene (DNFB), drugs were given systemically
      (25 mg/kg cyclosporin A, rapamycin; 2.5 mg/kg FK-506) and topically (0.02% and
      2%) at the time of DNFB challenge or several hours after and were assessed with
      respect to erythema and the numbers of infiltrating T lymphocytes entering skin
      challenge sites. FK-506, at all concentrations, significantly inhibited both T
      cell infiltration and skin reddening when used by both routes. Rapamycin
      displayed no inhibitory effect, whereas cyclosporin A only suppressed the
      erythema response when given systemically. The inhibition of normal human
      keratinocyte growth by the drugs was assessed using a protein dye-binding assay.
      After 2 weeks, FK-506 had no effect, whereas cyclosporin A and rapamycin both
      inhibited keratinocyte growth in a dose-dependent fashion and almost equivalently
      in serum-containing and serum-free keratinocyte growth medium. The findings
      showed that in vivo only FK-506 suppressed T-cell involvement in sensitized
      animals. In contrast, it failed to have any effect on keratinocyte growth,
      whereas rapamycin was more potent than cyclosporin A in inhibiting their
      proliferation. The future benefit of these drugs in dermatology may ultimately
      lie in their combined use.

PMID- 7507157
TI  - Correlation between histologic features and glomerular permeability in membranous
      nephropathy and immunoglobulin A nephropathy.
AB  - We evaluated the correlation between histologic features and glomerular
      permselectivity based on fractional clearances of dextrans relative to inulin
      (FCsDex). The subjects consisted of 12 healthy volunteers, 18 patients with
      membranous nephropathy, and 20 patients with immunoglobulin A nephropathy. In
      membranous nephropathy, FCsDex measured with large dextrans (radii larger than 56
      A) increased as the capillary lesion progressed. Histologic examination showed
      that glomerular capillary alteration was the factor most closely linked to
      changes in FCsDex in membranous nephropathy. Proteinuria (normalized to
      glomerular filtration rate) did not correlate with FCsDex. Increased FCsDex
      tended to normalize during prednisolone treatment in membranous nephropathy. In
      immunoglobulin A nephropathy, the impairment of glomerular size selectivity
      depended on the degree of mesangial sclerosis and tubulointerstitial injury. FCs
      of dextrans of 59 A were correlated with the mesangial sclerosis index (r =
      0.573, p = 0.050) and the tubulointerstitial injury index (r = 0.707, p = 0.003).
      Proteinuria (again normalized to glomerular filtration rate) was significantly
      correlated with FCs of large dextrans in immunoglobulin A nephropathy (r = 0.668,
      p = 0.008). We conclude that glomerular size-selective barriers were impaired
      both in membranous nephropathy and immunoglobulin A nephropathy. However, the
      mechanisms of impaired size selectivity might differ, at least in part, between
      these nephropathies. The predominant factors responsible for the size-selective
      defect seemed to be glomerular capillary wall lesions in membranous nephropathy
      but mesangial sclerosis or tubulointerstitial damages (or both) in immunoglobulin
      A nephropathy.

PMID- 7507159
TI  - Primary squamous carcinoma of the thyroid--a case report.
AB  - We report a well-documented case of fatal thyroid cancer with histopathological
      characteristics of primary squamous carcinoma. A possible primary tumour
      elsewhere was excluded. The possible histogenesis of this unusual tumour and the
      therapy of choice are briefly discussed.

PMID- 7507158
TI  - The behaviour of tympanic membrane perforations in tissue culture: a scanning
      electron microscopic study.
AB  - The effects of keeping rat tympanic membranes with an artificially made pars
      tensa perforation in tissue culture were observed under a scanning electron
      microscope. After one day and onwards, spreading and thickening of the
      keratinizing, outer squamous epithelium (OE) was noted. In addition, ballooning
      of the innermost cells of the outer epithelium apposing the inner tympanic
      epithelium (IE) was seen. No appreciable reaction was noted in the connective
      tissue layer of the drum. The inner tympanic epithelium appeared to be swollen,
      containing spherical structures in the cytoplasm, especially close to the area of
      contact with the outer meatal epithelium. No complete cover of the drum defect
      was seen after 14 days of tissue culture. Hyperplasia and spreading of the
      keratinizing, outer squamous epithelium of the drum is not sufficient to achieve
      covering of a drum perforation and complete healing cannot take place unless
      supported by granulation tissue formation.

PMID- 7507156
TI  - Membrane defence against complement lysis: the structure and biological
      properties of CD59.
AB  - The complement system is an important branch of the innate immune response,
      constituting a first line of defence against invading microorganisms which
      activate complement via both antibody-dependent and -independent mechanisms.
      Activation of complement leads to (a) a direct attack upon the activating cell
      surface by assembly of the pore-forming membrane attack complex (MAC), and (b)
      the generation of inflammatory mediators which target and recruit other branches
      of the immune system. However, uncontrolled complement activation can lead to
      widespread tissue damage in the host, since certain of the activation products,
      notably the fragment C3b and the C5b-7 complex, can bind nonspecifically to any
      nearby cell membranes. Therefore it is important that complement activation is
      tightly regulated. Our own cells express a number of membrane-bound control
      proteins which limit complement activation at the cell surface and prevent
      accidental complement-mediated damage. These include decay-accelerating factor,
      complement receptor 1 and membrane cofactor protein, all of which are active at
      the level of C3/C5 convertase formation. Until recently, cell surface control of
      MAC assembly had been attributed to a single 65-kD membrane protein called
      homologous restriction factor (alternatively named C8-binding protein and MAC
      inhibiting protein). However a second MAC-inhibiting protein has since been
      discovered and it is now clear that this protein plays a major role in the
      control of membrane attack. This review charts the rapid progress made in
      elucidating the protein and gene structure, and the mechanism of action of this
      most recently discovered complement inhibitor, CD59.

PMID- 7507160
TI  - Autopsy report of acute necrotizing opticomyelopathy associated with thyroid
      cancer.
AB  - We report an autopsied case of paraneoplastic necrotizing myelopathy. The patient
      had bilateral blindness, quadriplegia, and dyspnea of acute onset and died
      without remission 7 weeks later. The severe tissue necrosis and demyelination
      were found in the optic chiasm and from the medulla oblongata throughout the
      whole length of spinal cord. A papillary carcinoma was found in the thyroid gland
      at autopsy. In the present case IgG, myelin basic protein and activated helper T
      cells were increased in the CSF at onset, suggesting a mechanism of autoimmune
      demyelination for the condition.

PMID- 7507161
TI  - Low diagnostic yield of sural nerve biopsy in patients with peripheral neuropathy
      and primary amyloidosis.
AB  - Patients with primary amyloidosis may develop peripheral neuropathy as an early
      feature. Sural nerve biopsy is reported to be a sensitive method for diagnosing
      amyloidosis in such patients. We identified nine patients, ultimately diagnosed
      as having amyloidosis, who were referred for peripheral neuropathy of
      undetermined etiology. In six, a sural nerve biopsy demonstrated no amyloid.
      Subsequent examination of other tissue or of the contralateral sural nerve
      eventually resulted in the correct diagnosis. We conclude that sural nerve biopsy
      may be less sensitive than previously believed for the diagnosis of amyloidosis
      in patients with peripheral neuropathy secondary to amyloid. When the clinical
      suspicion of amyloidosis is high, a nondiagnostic sural nerve biopsy should not
      discourage the performance of further investigative studies.

PMID- 7507163
TI  - The effect of silymarin and gamma radiation on nucleic acids in rat organs.
AB  - The influence of silymarin on radiation-induced changes in concentrations of RNA
      and DNA was followed in male Wistar rats. The liver, spleen and bone marrow were
      examined at 30 h, 7, 14 and 21 days after 6 Gy whole-body gamma irradiation or 30
      h and 7 days after 3 Gy whole-body gamma irradiation. Following silymarin
      treatment, a mild increase in the concentration and total content of RNA and DNA
      in liver and bone marrow at days 7 and 14 after administration was found; in
      spleen, total content of DNA significantly increased at 30 h. Silymarin
      administered 1 h before irradiation, moderated radiation-induced changes in
      nucleic acids in its target organ, liver, and in spleen and bone marrow. We
      suggest that beneficial effects of silymarin on radiation injury to the membranes
      of liver cells resulted primarily from its antioxidative ability and its ability
      to act as a radical scavenger, thereby preventing membrane permeability changes.

PMID- 7507162
TI  - Prognostic relevance of epidermal growth factor receptor (EGF-R) and c-neu/erbB2
      expression in glioblastomas (GBMs).
AB  - Seventeen untreated primary adult glioblastomas were analyzed using
      immunocytochemistry for the expression of EGF-R, c-neu/erbB2, TGF-alpha, and
      phosphotyrosine. Patients were divided by median survival into long-term or short
      term survivors (LTS, N = 10, median > 4 years; versus STS, N = 7, median 61
      weeks). There were no significant differences between the two groups in terms of
      age, extent of resection, post-operative Karnofsky status, or treatment.
      Diagnostic sections from each tumor were stained with antibodies to EGF-R, c
      neu/erbB2, TGF-alpha and phosphotyrosine. Double-labelling for TGF-alpha and EGF
      R was also performed. All 10/10 LTS were considered to be EGF-R negative/scant,
      while 4/7 STS were EGF-R positive. EGF-R negativity significantly correlated with
      long-term survival. The differences in c-neu/erbB2 expression did not reach
      significance. However, 4/7 STS were positive for both proteins and 76% of the 17
      cases were either double negative or positive for EGF-R and c-neu/erbB2. TGF
      alpha and phosphotyrosine were frequently expressed, but neither were prognostic.
      Recurrent tumors were studied in 7 STS. EGF-R expression was increased in 4/7 of
      these cases and c-neu/erbB2 was increased in all 7 cases, compared to the
      pretreatment baselines. Increased expression of these proteins in glioblastomas
      may be associated with aggressive clinical behavior and treatment resistance.

PMID- 7507164
TI  - Inhibitory effect of CP-96,345, a non-peptide neurokinin-1-receptor antagonist,
      on neurogenic responses of guinea-pig isolated airway smooth muscle.
AB  - The actions of CP-96,345, a non-peptide neurokinin-1 receptor antagonist, on the
      responses evoked by electrical-field stimulation or by acetylcholine and
      substance P in guinea-pig tracheal and bronchial muscle strips were examined.
      Electrical-field stimulation evoked a biphasic response, consisting of a
      cholinergically-mediated fast contraction followed by non-adrenergically-mediated
      relaxation in tracheal muscle and by a non-cholinergically-mediated slow
      contraction in bronchial muscle. CP-96,345 (1-10 microM) caused a concentration
      dependent and non-selective inhibition in the amplitude of these neurogenic
      responses, where non-cholinergic contractions were more profoundly inhibited.
      Submaximal contractions of tracheal and bronchial muscles evoked by exogenous
      substance P (0.1-3 microM) were partly inhibited by CP-96,345 (1-10 microM), but
      acetylcholine-induced contractions were hardly inhibited. The results indicate
      that in guinea-pig isolated airway smooth muscle CP-96,345 can non-selectively
      inhibit neurogenic responses probably via neurokinin-1 receptor-dependent and
      independent mechanisms.

PMID- 7507165
TI  - Design and synthesis of novel cyclic RGD-containing peptides as highly potent and
      selective integrin alpha IIb beta 3 antagonists.
AB  - Utilizing conformational constraints in conjunction with various structural
      considerations, we have synthesized a series of cyclic disulfide peptides that
      are highly potent and selective antagonists for the platelet integrin alpha IIb
      beta 3 (GPIIb/IIIa). The affinities of the peptides for alpha IIb beta 3 were
      determined by platelet aggregation assays and an alpha IIb beta 3 ELISA. Their
      affinities for alpha 5 beta 1 and alpha v beta 5 integrins were also determined
      in respective ELISA assays. Structure-activity relationship studies suggest that
      R-G-D-Ar-R (Ar = hydrophobic residue) is the essential pharmacophore that is
      responsible for their high alpha IIb beta 3 binding affinity, very high
      selectivity, and distinct biological properties. One of these analogues, TP9201,
      has been shown to inhibit platelet-mediated thrombus formation without associated
      prolongation of template bleeding time. The arginine residue adjacent the carboxy
      terminus of the R-G-D-Ar sequence could function as the biological effector
      element that determines this distinct and unexpected biological property.

PMID- 7507166
TI  - Antigenic mimicry of Clostridium chauvoei flagella by polyclonal anti-idiotypic
      antibodies.
AB  - Polyclonal rabbit anti-idiotypic (anti-Id) antibodies against two monoclonal
      antibodies (MAbs) specific for the flagella of Clostridium chauvoei were
      produced, purified and characterised. Lack of cross-reactivity with heterologous
      MAbs indicated that the anti-Id antibodies were highly specific. The surface
      exposed epitopes of the flagellar filament recognised with protective MAb were
      further distinguished by the anti-Id antibodies. Moreover, each anti-Id antibody
      inhibited the binding of its related MAb to flagellar antigens in a competitive
      enzyme-linked immunosorbent assay, suggesting that the anti-Id antibodies bore an
      internal image of the flagellar antigens. The survival rate of mice was increased
      to nearly twice that of controls by immunisation with anti-Id 41, which had been
      produced with a protective MAb; in contrast, anti-Id 114, produced with a non
      protective MAb, failed to immunise. The results suggest that an anti-Id antibody
      containing an internal image of C. chauvoei flagella might be used as a vaccine.

PMID- 7507167
TI  - Post-transcriptional regulation of the str operon in Escherichia coli. Ribosomal
      protein S7 inhibits coupled translation of S7 but not its independent
      translation.
AB  - The str operon of Escherichia coli consists of the genes for ribosomal proteins
      S12 (rpsL) and S7 (rpsG) and elongation factors G (fusA) and Tu (tufA). Previous
      studies have shown that S7 is a translational feedback repressor and inhibits the
      synthesis of itself and of elongation factor G. We have now shown that induction
      of S7 synthesis from the S7 gene fused to the arabinose promoter on a plasmid
      also leads to inhibition of the synthesis of S12 from the chromosomal S12 gene,
      and that this regulation takes place using the same target site as that used for
      distal gene regulation, i.e. S7 retroregulates S12. We have then demonstrated
      that S7 synthesis is mostly translationally coupled with the translation of the
      preceding S12 gene. Using a rpsG'-'lacZ fusion gene as a reporter for S7
      synthesis, we found that abolishing S12 translation by a mutational alteration of
      the AUG start codon of the S12 gene leads to about tenfold reduction of S7
      synthesis without significantly affecting its rate of transcription. Deletion of
      the proximal portion of the S12 gene or a premature termination of S12
      translation by an amber mutation at the 26th codon also led to a large reduction
      of S7 synthesis. Unexpectedly, we have discovered that overproduction of S7 in
      trans from a plasmid leads to repression of the rpsG'-'lacZ fusion gene when the
      fusion gene is preceded by the intact S12 gene, but not when the S12 gene carried
      the above-mentioned mutations that abolish S12 translation. Thus, a novel feature
      of this regulatory system is that translation of S7 achieved by independent
      initiation is not inhibited by S7 in vivo, whereas translation of S7 achieved by
      translational coupling is sensitive to S7 repression. These observations also
      suggest that the coupled S7 translation is probably achieved by the use of
      ribosomal subunits employed for translation of the upstream S12 gene.

PMID- 7507168
TI  - In vitro genetic analysis of the hinge region between helical elements P5-P4-P6
      and P7-P3-P8 in the sunY group I self-splicing intron.
AB  - Modeling of the group I intron RNA suggests that its catalytic core is primarily
      composed of two extended structural elements (stacked helices P5-P4-P6 and P7-P3
      P8) whose relative orientation is partially determined by base-triple
      interactions between paired regions P4 and P6, and single-stranded joining
      regions J6/7 and J3/4, respectively. In vitro genetic selection was used to
      isolate functional sequence variants of the proposed triple helical domain of the
      sunY intron. Comparative sequence analysis of the selected variants provided
      supporting evidence for the two previously established base-triples between P4
      and J6/7 and provided the first experimental evidence for an interaction between
      P6(1) and J3/4(3). Sequence covariations also indicated that a simple
      relationship exists between the length of a single-stranded joining region, J3/4,
      and the identity of a particular base-pair, P4(1). Selected variants based on a
      core structure with an extra nucleotide inserted in J3/4 revealed two different
      responses to this structural perturbation: a base-triple interaction and an
      intrahelical bulged pyrimidine. Chemical modification analysis supported the
      existence of these alternative structures. The function of this region of the
      ribozyme can therefore be fulfilled by at least three different structures.

PMID- 7507169
TI  - A monoclonal antibody epitope on keratin 8 identified using a phage peptide
      library.
AB  - A bacteriophage random hexapeptide library was used to define the epitope of a
      monoclonal anti-keratin antibody. Phage selected by the keratin 8-specific
      antibody LE41 displayed highly related sequences on their pIII coat protein. The
      consensus sequence S(X)LNP allowed the precise localization of an LE41 epitope
      (SLLSP) within the head domain (H1 subdomain) of human keratin 8, known to be
      important for correct filament polymerisation. By sequencing the immunizing
      antigen, keratin 8 from Potorous tridactylis, it was shown that the natural
      epitope of LE41 is the pentapeptide SLLNP, which confirmed predictions from the
      phage library results. An SLL(X)P motif is found in the H1 region of all type II
      keratins (keratins 1 to 8) in different species, but mutational analysis revealed
      that LE41 can only bind to keratin 8 when Asn (N) or Ser (S) is found in the (X)
      position. Thus the monoclonal antibody LE41 retains its specificity for keratin
      8, dependent on a single amino acid residue, even though it recognizes an epitope
      within the highly conserved H1 subdomain of the head region. Six other monoclonal
      antibodies tested on the phage library failed to select motifs.

PMID- 7507170
TI  - Defining the requirements for an antibody epitope on influenza virus
      neuraminidase: how tolerant are protein epitopes?
AB  - To determine the conformational requirements for antibody recognition and extent
      of flexibility within a protein epitope, a chimeric influenza A virus
      neuraminidase (NA) has been constructed in which five discontinuous polypeptide
      segments from a subtype N9 NA, which comprise the monoclonal antibody NC41
      epitope, have been grafted onto a subtype N2 NA. The resulting chimeric NA was
      expressed, assembled as a tetramer, and transported to the cell surface, but was
      not recognized by NC41 in immunoprecipitation experiments or by surface
      immunofluorescence. Although the N2 and N9 protein folds are identical and this
      chimera contains all the antibody contacts as defined by the crystal structure of
      the complex, NC41 binding was not achieved. Modeling studies suggest that at
      least one polypeptide segment is displaced from its normal position which would
      account for the observed lack of enzyme activity as well as lack of antibody
      binding. This implies that in addition to the specific critical interactions
      between NA and Fab residues required for antibody binding, the overall
      arrangement of amino acids within an epitope must be in a specific orientation
      that is necessary for initial antibody recognition.

PMID- 7507171
TI  - PUZZLE: a new method for automated protein docking based on surface shape
      complementarity.
AB  - We describe here a novel procedure for automated protein docking, based only on
      geometric criteria. In our algorithm we project protein surfaces into bi
      dimensional matrices; the search for complementary regions is performed by
      detecting matching sub-matrices. An exhaustive sampling of the rotation space is
      made in order to analyse all the possible relative orientations of the two
      proteins, but nevertheless this procedure requires a relatively short processing
      time (3 h to 24 h cpu time on a SG4D320, depending on the complexity of the input
      information). When tested with co-crystallized, free components and models of
      components of known protein-protein complexes, the method gave very satisfactory
      results. The procedure selects no more than four relative orientations of the
      molecular components, but the correct orientation is always present among them,
      ranking either first or second. In more than half the cases the "wrong" solutions
      nevertheless correctly identify most of the residues involved in the interaction.
      This is remarkable also in view of the fact that the chosen test complexes
      (trypsin-trypsin inhibitor and antibody-lysozyme) have a very different geometry
      of surface complementarity: trypsin inhibitor inserts a long side-chain into the
      deep specificity pocket of the protease, while the interface between antibody and
      lysozyme is rather flat and contains buried water molecules (not included in the
      calculation). In order to simulate a more realistic protein docking problem, we
      also used a trypsin inhibitor and an anti-lysozyme antibody model in our
      simulations, again with satisfying results.

PMID- 7507172
TI  - 1H NMR analysis of the partly-folded non-native two-disulphide intermediates (30
      51,5-14) and (30-51,5-38) in the folding pathway of bovine pancreatic trypsin
      inhibitor.
AB  - The conformational properties of analogues of the (30-51,5-14) and (30-51,5-38)
      disulphide intermediates in refolding of reduced BPTI, with non-native second
      disulphide bonds, have been characterized in detail by 1H NMR analysis. They are
      shown to have partly-folded conformations, very similar to that of the (30-51)
      one-disulphide intermediate from which they arise during folding. The non-native
      disulphide bonds are formed in flexible or unfolded parts of the polypeptide
      chain; they do not disrupt the folded portion nor do they introduce substantial
      non-native conformation. The conformational properties of these intermediates
      explain their important roles in the folding pathway.

PMID- 7507173
TI  - Prediction of protein side-chain conformations from local three-dimensional
      homology relationships.
AB  - A method for predicting the conformations of protein side-chains, starting from
      main-chain co-ordinates alone, is described. The method involves the comparison
      of the local environment of each residue whose side-chain conformation is to be
      predicted with a database of local environments for the same residue type
      constructed from an analysis of high-resolution protein structures. Local
      environments are described in terms of the residue type and location in space of
      residues that interact with the side-chain of interest. The best (most three
      dimensionally homologous) few matches to each residue are then input to a Monte
      Carlo procedure to give a final predicted structure. The method has been tested
      on a selection of eight proteins, ranging in size from 46 to 323 amino acid
      residues. The average side-chain atom root-mean-square deviation between the
      actual and predicted structures is 1.71 A taken over all residues, and 1.00 A if
      restricted to buried residues. Over all residues, an average of 59.8% of all side
      chain dihedral angles are predicted within +/- 30 degrees of the crystal
      structure values. Considering buried residues only, this rises to 79.6%.

PMID- 7507174
TI  - Mutations in 23 S ribosomal RNA perturb transfer RNA selection and can lead to
      streptomycin dependence.
AB  - Escherichia coli ribosomes with a G to C transversion at position 2661 in 23 S
      ribosomal RNA are more accurate in tRNA selection than wild-type ribosomes. This
      enhanced accuracy is due to improved initial selection of ternary complexes
      rather than proofreading of aminoacyl tRNAs. The 2661C mutation reduces the
      binding rate of cognate ternary complexes to the A-site. This binding rate
      deficiency becomes dramatic when ribosomes also harbour an S12 mutation with a
      streptomycin-resistant, hyperaccurate phenotype. In this case, severe loss of
      kinetic efficiency in EF-Tu function leads to cell death. Streptomycin restores
      viability by increasing the association rate of ternary complex to these doubly
      altered ribosomes. The binding rate of EF-G to 2661C ribosomes is also reduced
      while the translocation rate is unaffected.

PMID- 7507175
TI  - Membrane-bound form of the pore-forming domain of colicin A. A neutron scattering
      study.
AB  - The ion-channel forming C-terminal fragment of colicin A binds to negatively
      charged lipid vesicles and provides an example of the insertion of a soluble
      protein into a lipid bilayer. The soluble structure is known and consists of a
      ten-helix bundle containing a hydrophobic helical hairpin. This fragment forms a
      well-defined complex with dimyristoylphosphatidyl-glycerol which is thus amenable
      to neutron scattering studies. Neutron scattering experiments in the Guinier
      range (low angles) provided the mass and the stoichiometry of the complex
      (290,000 (+/- 10,000) M(r), 8.2 (+/- 0.5)), in fair agreement with previous
      determinations. By varying the neutron scattering length density of the solvent
      with 2H2O/H2O mixtures and therefore the contrast of the different components,
      the radial distribution of the protein and of the lipids was determined. Finally,
      an attempt was made to fit various models to the wider angle scattering data.
      This study suggests that the pore-forming fragment of colicin A lies mostly at
      the surface of the membrane, with the lipids arranged in a bilayer organization.

PMID- 7507176
TI  - Comparison of surface accessible residues in human and murine immunoglobulin Fv
      domains. Implication for humanization of murine antibodies.
AB  - Statistical analysis of a database of unique human and murine immunoglobulin
      heavy chain and light chain variable regions reveals that the precise patterns of
      exposed residues are different in human and murine antibodies, while most
      individual surface positions have strong preferences for a small number of
      residue types. Consideration of these surface patterns alone generates almost
      identical family groupings for light and heavy chain variable domain sequences to
      those produced by methods such as those of Kabat et al., where N-terminal
      framework sequences only are compared, or Tomlinson et al., in which entire
      variable region nucleotide sequences are used. This unexpected result suggests
      that the surfaces of V-regions are at least as well conserved as the core
      framework sequences. Furthermore, using these patterns of human and murine
      surface residues a novel method for the "humanization" of murine antibodies has
      been developed and tested.

PMID- 7507177
TI  - An epitope proximal to the carboxyl terminus of the alpha-subunit is located near
      the lobe tips of the phosphorylase kinase hexadecamer.
AB  - An epitope of the alpha-subunit of phosphorylase kinase from fast-twitch skeletal
      muscle was localized to the tips of the bilobal kinase molecule by two types of
      immunoelectron microscopy. This is the first direct evidence identifying the
      location of any of the enzyme's 16 subunits within the phosphorylase kinase
      molecule. Negatively stained complexes of phosphorylase kinase with an
      immunoglobulin G monoclonal antibody specific for the alpha-subunit (mAb 157)
      were observed by conventional transmission electron microscopy, and complexes of
      the unstained enzyme with undecagold-labeled Fab' fragments derived from mAb 157
      were visualized by scanning transmission electron microscopy. Images from both
      techniques indicate a symmetrical arrangement of the epitope, consistent with a
      "head-to-head" packing arrangement of the four alpha-subunits. In Western blots,
      mAb 157 crossreacted with comigrating fragments obtained by digesting non
      denatured phosphorylase kinase with a variety of proteases, suggesting that the
      epitope for the anti-alpha mAb is contained within a protease-resistant domain.
      Partial sequencing of a 24.1 kDa immunoreactive chymotryptic fragment narrowed
      the epitope to somewhere within the carboxyl-terminal one-sixth of the alpha
      subunit. Studies of the crossreactivity of mAb 157 with the holoenzyme in the
      presence of calmodulin, after phosphorylation or with different isoforms (all
      with known alpha-subunit sequence targets or differences), suggest that the
      epitope is even more proximal to the carboxyl terminus. This epitope was not
      implicated in any known function or activity of the enzyme, suggesting that the
      region proximal to the carboxyl terminus of the alpha-subunit, and thus to the
      lobe tips of the hexadecamer, may have a role other than catalytic or regulatory.

PMID- 7507179
TI  - Characterization of the polyadenylation signal of influenza virus RNA.
AB  - It has been shown that a stretch of uridines (U's) near the 5' end of the virion
      RNA of influenza A virus is the polyadenylation site for viral mRNA synthesis. In
      addition, the RNA duplex made up the 3' and 5' terminal sequences adjacent to the
      U stretch is also involved in polyadenylation. We have further characterized the
      polyadenylation signal of influenza virus RNA with a ribonucleoprotein
      transfection system. We found that the optimal length of the U stretch is 5 to 7
      uridine residues. We also showed that the upstream sequence at the 5' end is not
      involved in polyadenylation and that the optimal distance between the 5' end and
      the U stretch is 16 nucleotides. The combination of these features defines the
      polyadenylation site and differentiates this signal from other U stretches
      scattered throughout the genomes of influenza viruses.

PMID- 7507178
TI  - Isolation and characterization of simian T-cell leukemia virus type II from New
      World monkeys.
AB  - Since the description of human T-cell leukemia virus type I (HTLV-I) and its
      simian counterpart, simian T-cell leukemia virus type I (STLV-I), the possible
      existence of other related simian retroviruses has been raised. Here, we report a
      new retrovirus, STLV-II, which we have identified in spider monkeys (Ateles
      fusciceps), a New World primate species. Initially, a recombinant HTLV-II
      envelope protein (RP-IIB) was used to identify anti-STLV-II antibodies in New
      World monkeys by Western blot (immunoblot) assays. Subsequently, the virus was
      characterized by Southern blot hybridization, which showed that STLV-II and HTLV
      II have a high degree of nucleotide sequence homology but have different
      restriction enzyme patterns. Nucleotide sequence analysis of the pX-II region of
      STLV-II provirus revealed 3% variation with the corresponding region of HTLV-II.
      Electron micrographic studies revealed HTLV-like, type C retrovirus particles
      outside the cell membranes of STLV-II-infected cells. This study describes the
      first link between HTLV-II and a simian reservoir in the New World. Further
      molecular studies of STLV-II infection in different species of New World monkeys,
      especially from the wild, may provide valuable information about the origin and
      intragroup relationships of South American monkeys. Spider monkeys infected with
      STLV-II may serve as an important animal model for HTLV-II infection in humans.

PMID- 7507181
TI  - A specific orientation of RNA secondary structures is required for initiation of
      reverse transcription.
AB  - The 5' end of avian retrovirus RNA near the primer-binding site (PBS) forms two
      secondary structures, the U5-inverted repeat (U5-IR) and the U5-leader stems, and
      contains a 7-nucleotide sequence that anneals to the T psi C loop of the
      tRNA(Trp) primer. Mutations that disrupt any of these base pair interactions
      cause defects in initiation of reverse transcription both in vivo and in vitro
      (D. Cobrinik, A. Aiyar, Z. Ge, M. Katzman, H. Huang, and J. Leis, J. Virol.
      65:3864-3872, 1991; A. Aiyar, D. Cobrinik, Z. Ge, H.-J. Kung, and J. Leis, J.
      Virol. 66:2464-2472, 1992). We have now examined the effect of perturbing the non
      base-paired intervening "spacer" sequences between these secondary-structure
      elements. Small deletions or insertions in these intervening sequences decreased
      initiation of reverse transcription in vitro. In contrast, base substitutions,
      which maintain the spacing distances between the structures, had no detectable
      effect. Additionally, a small deletion at the 3' end of the PBS caused a
      significant decrease in initiation of reverse transcription whereas substitution
      mutations again had no effect. Together, these results indicate that reverse
      transcriptase forms a complex in which the different structural elements are
      maintained in a specific orientation that is required for efficient initiation of
      reverse transcription. Specific sequence recognition of the duplex structures by
      reverse transcriptase is also required since mosaic RNAs that combine the human
      immunodeficiency virus type 1 PBS with avian sequences is not efficiently
      utilized for reverse transcription even though the primer used can anneal to the
      substituted PBS.

PMID- 7507180
TI  - Kinetics of human immunodeficiency virus type 1 reverse transcription in blood
      mononuclear phagocytes are slowed by limitations of nucleotide precursors.
AB  - Human immunodeficiency virus type 1 infection of mononuclear phagocytes has been
      implicated in disease manifestations, but postentry viral replication events in
      these cells have not been well characterized. Productive infection of activated T
      cells is associated with cell proliferation and accumulation of full-length viral
      DNA within 6 h. In infected, nondividing quiescent peripheral blood lymphocytes,
      reverse transcription is aborted prior to full-length viral DNA formation. For
      nondividing, cultured mononuclear phagocytes, we now report a third pattern of
      reverse transcription with relatively slow kinetics, in which full-length viral
      DNA did not accumulate until 36 to 48 h. The reverse transcription rate in
      mononuclear phagocytes could be accelerated by addition of exogenous nucleotide
      precursors, but still not to the rate seen in activated T cells. These results
      indicate that substrate limitations in mononuclear phagocytes slow but do not
      arrest human immunodeficiency virus type 1 reverse transcription.

PMID- 7507182
TI  - Rapid phenotypic reversion of zidovudine-resistant feline immunodeficiency virus
      without loss of drug-resistant reverse transcriptase.
AB  - We have selected and plaque purified zidovudine (3'-azido-3'-deoxythymidine
      [AZT])-resistant mutants from an infectious molecular clone of feline
      immunodeficiency virus (FIV). The patterns of cross-resistance and drug
      susceptibilities of these mutants were similar to those of the AZT-resistant FIV
      that we previously selected in vitro from a wild-type FIV population and to those
      of the most common AZT-resistant clinical isolates of human immunodeficiency
      virus type 1. Two AZT-resistant mutants of FIV, one selected from a normal
      population and one selected from the molecular clone, each reverted rapidly to an
      AZT-sensitive phenotype when passaged in the absence of drug. Sequence analysis
      of the reverse transcriptase (RT)-encoding region from the plaque-purified AZT
      resistant FIV revealed a single base change at position 2939, resulting in a Glu
      to-Lys substitution at amino acid 202 of the RT. Similar analyses of plaque
      purified revertants showed that the phenotypic reversion was not the result of a
      genotypic reversion at this position and that no additional mutations existed
      within the RT-encoding region of the revertants. Moreover, RTs purified from the
      mutant and revertant were both resistant to the 5'-triphosphate of AZT. These
      results indicate the complexity of AZT resistance and suggest the presence of
      additional factors, outside the RT-encoding region, which may contribute to AZT
      resistance.

PMID- 7507183
TI  - Distinct modes of human immunodeficiency virus type 1 proviral latency revealed
      by superinfection of nonproductively infected cell lines with recombinant
      luciferase-encoding viruses.
AB  - To study the basis of cellular latency of human immunodeficiency virus (HIV), we
      have used a recombinant luciferase-encoding HIV (HXB-Luc) to superinfect
      nonproductively HIV-1-infected human leukemic cell lines. HXB-Luc contains the
      Photinus pyralis luciferase gene in place of the nef gene and provides a highly
      sensitive, simple assay for HIV infection and expression. To circumvent any
      superinfection block in latently infected cells, we also generated viruses
      pseudotyped with murine leukemia virus amphotropic envelope (HXB-Luc:ampho). The
      parental uninfected lines, U937 and A3.01, from which the latently infected cell
      lines U1 and ACH-2, respectively, were derived could be readily infected with
      pseudotyped or nonpseudotyped reporter viruses. However, superinfection of U1
      cells with either HXB-Luc or HXB-Luc:ampho resulted in only low levels of
      luciferase activity. Like the endogenous provirus, HXB-Luc provirus could be
      efficiently activated by phorbol ester treatment of HXB-Luc:ampho-superinfected
      U1 cells. In contrast, superinfection of ACH-2 cells resulted in active
      expression of the secondarily introduced virus even in unstimulated cells and
      luciferase production higher than in the parental cell line A3.01. Thus, the
      proviral latency in U1 cells appears to result from a defect in the cellular
      environment (a trans effect), whereas the latency in ACH-2 is specific to the
      integrated provirus and is probably a cis effect due to the site of integration.
      These results demonstrate distinct modes of proviral latency in these two cell
      line models and may have implications in our understanding of the regulation and
      significance of cellular latency in HIV infection.

PMID- 7507184
TI  - Resistance to neutralization by broadly reactive antibodies to the human
      immunodeficiency virus type 1 gp120 glycoprotein conferred by a gp41 amino acid
      change.
AB  - A neutralization-resistant variant of human immunodeficiency virus type 1 (HIV-1)
      that emerged during in vitro propagation of the virus in the presence of
      neutralizing serum from an infected individual has been described. A threonine
      for-alanine substitution at position 582 in the gp41 transmembrane envelope
      glycoprotein of the variant virus was responsible for the neutralization
      resistant phenotype (M.S. Reitz, Jr., C. Wilson, C. Naugle, R. C. Gallo, and M.
      Robert-Guroff, Cell 54:57-63, 1988). The mutant virus also exhibited reduced
      sensitivity to neutralization by 30% of HIV-1-positive sera that neutralized the
      parental virus, suggesting that a significant fraction of the neutralizing
      activity within these sera can be affected by the amino acid change in gp41 (C.
      Wilson, M. S. Reitz, Jr., K. Aldrich, P. J. Klasse, J. Blomberg, R. C. Gallo, and
      M. Robert-Guroff, J. Virol. 64:3240-3248, 1990). It is shown here that the change
      of alanine 582 to threonine specifically confers resistance to neutralizing by
      antibodies directed against both groups of discontinuous, conserved epitopes
      related to the CD4 binding site on the gp120 exterior envelope glycoprotein. Only
      minor differences in binding of these antibodies to wild-type and mutant envelope
      glycoproteins were observed. Thus, the antigenic structure of gp120 can be subtly
      affected by an amino acid change in gp41, with important consequences for
      sensitivity to neutralization.

PMID- 7507185
TI  - Inhibition of complement-mediated cytolysis by the terminal complement inhibitor
      of herpesvirus saimiri.
AB  - Herpesvirus saimiri (HVS) is a lymphotropic herpesvirus that induces T-cell
      transformation in vitro and causes lymphomas and leukemias in New World primates
      other than its natural host, the squirrel monkey. Nucleotide sequence analysis of
      the HVS genome revealed two open reading frames with significant homology to
      genes for human complement regulatory molecules. One of these genes encodes a
      predicted protein (designated HVSCD59) with 48% amino acid sequence identity to
      the human terminal complement regulatory protein CD59 (HuCD59). The CD59 homolog
      from squirrel monkey (SMCD59) was cloned, and the corresponding amino acid
      sequence showed 69% identity with HVSCD59. BALB/3T3 cells stably expressing
      HVSCD59, SMCD59, or HuCD59 were equally protected from complement-mediated lysis
      by human serum. However, only HVSCD59-expressing cells were effectively protected
      from complement-mediated lysis when challenged with rat serum, suggesting that
      HVSCD59 was less species restrictive. The complement regulatory activity of
      HVSCD59 and SMCD59 occurred after C3b deposition, indicating terminal complement
      inhibition. Treatment of BALB/3T3 stable transfectants with phosphatidylinositol
      specific phospholipase C prior to complement attack decreased the complement
      regulatory function of HVSCD59, suggesting cell surface attachment via a glycosyl
      phosphatidylinositol anchor. Cells expressing HVSCD59 effectively inhibited
      complement-mediated lysis by squirrel monkey serum in comparison with SMCD59
      expressing cells. Finally HVSCD59-specific transcripts were detected in owl
      monkey cells permissive for lytic HVS replication but not in T cells transformed
      by HVS, which failed to produce virions. These data are the first to demonstrate
      a functional, virally encoded terminal complement inhibitor and suggest that
      HVSCD59 represents a humoral immune evasion mechanism supporting the lytic life
      cycle of HVS.

PMID- 7507187
TI  - Mechanism of enhancement of DNA expression consequent to cointernalization of a
      replication-deficient adenovirus and unmodified plasmid DNA.
AB  - Given the knowledge that replication-deficient adenoviruses can mediate the
      delivery of unlinked plasmid DNA into eukaryotic cells (K. Yoshimura, M. A.
      Rosenfeld, P. Seth, and R. G. Crystal, J. Biol. Chem. 268:2300-2303, 1993), this
      study focuses on the role of receptor-mediated endocytosis in this process.
      AdCFTR (an E1- E3- adenovirus type 5-based replication-deficient adenovirus
      containing the 4.5-kb human cystic fibrosis transmembrane conductance regulator
      cDNA) was added to Cos-7 cells together with plasmid pRSVL (containing the Rous
      sarcoma virus long terminal repeat promoter followed by the luciferase cDNA), and
      luciferase activity was quantified as a measure of the expression of the plasmid
      DNA. When AdCFTR was bound to Cos-7 cells at 4 degrees C and the cells were
      subsequently incubated at 37 degrees C in the presence of pRSVL, the expression
      of luciferase activity was increased in proportion to the amount of AdCFTR added,
      reaching > 10(4)-fold at 3,000 PFU per cell. AdCFTR-mediated increase in pRSVL
      was inhibited by addition of purified adenovirus fiber but not hexon, suggesting
      cell surface adenovirus receptors were involved in the cointernalization process.
      Cell lines with a high number of adenovirus receptors (Cos-7 and HeLa) showed
      significant AdCFTR-dependent pRSVL expression, while cell lines with low numbers
      of adenovirus receptors (NIH 3T3 and U-937) showed little. AdCFTR-mediated
      increase in the expression of pRSVL was prevented when AdCFTR was heat treated
      and exposed to antibody against adenovirus or when the cointernalization process
      was evaluated in the presence of chloroquine, conditions all known to prevent
      adenovirus-mediated disruption of endocytic vesicles. In contrast, the uptake of
      AdCFTR into Cos-7 cells was not affected by any of these conditions. When AdCFTR
      was exposed to UV light, its ability to grow in 293 cells was obviated, but
      AdCFTR-dependent increase in pRSVL expression was minimally reduced. Finally,
      empty capsids of AdCFTR were able to enhance the delivery and expression of
      plasmid pRSVL into Cos-7 cells, suggesting that the adenovirus genome is not
      required for AdCFTR-mediated plasmid cointernalization. Together, these
      observations suggest that the ability of a replication-deficient recombinantly
      adenovirus to mediate the cointernalization and expression of plasmids is
      mediated by the receptor-mediated endocytosis pathway.

PMID- 7507186
TI  - Influenza virus M2 protein ion channel activity stabilizes the native form of
      fowl plague virus hemagglutinin during intracellular transport.
AB  - The influenza A/fowl plague virus/Rostock/34 hemagglutinin (HA), which is cleaved
      intracellularly and has a high pH threshold (pH 5.9) for undergoing its
      conformational change to the low-pH form, was expressed from cDNA in CV-1 and
      HeLa T4 cells in the absence of other influenza virus proteins. It was found, by
      biochemical assays, that the majority of the HA molecules were in a form
      indistinguishable from the low-pH form of HA. The acidotropic agent, ammonium
      chloride, stabilized the accumulation of HA in its native form. Coexpression of
      HA and the homotypic influenza virus M2 protein, which has ion channel activity,
      stabilized the accumulation of HA in its pH neutral (native) form, and the M2
      protein ion channel blocker, amantadine, prevented the rescue of HA in its native
      form. These data provide direct evidence that the influenza virus M2 protein ion
      channel activity can affect the status of the conformational form of cleaved HA
      during intracellular transport.

PMID- 7507189
TI  - Multiple coding and the evolutionary properties of RNA secondary structure.
AB  - This article evaluates evolutionary properties of the transition from RNA primary
      sequence to RNA secondary structure. It focuses on the restrictions that the
      conservation of a protein code in an RNA sequence puts on its potential to evolve
      towards a specific secondary structure. Restricting the mutations to those that
      do not affect the coding for a protein restricts both the accessibility and the
      connectivity of the sequence space. The accessibility is restricted because only
      certain point mutations are allowed. The connectivity is restricted because no
      insertions and deletions are allowed. Simulating an evolutionary search process
      for a specific secondary structure shows that (i) the reduction of allowable
      point mutations allows for adaptation to some large-scale topology, but strongly
      reduces the possibility of small-scale adaptations, (ii) the abolition of
      insertions and deletions has very little effect on the results of the search
      process. During the evolutionary search process for a secondary structure with a
      specific topology and a high frequency of base-pairing the quasispecies moves
      into a subspace in which the similarity between secondary structures of
      neighboring sequences is relatively high. Increased similarity between second
      structures of neighboring sequences is also found in the Rev responsive element
      (RRE) in the lentiviruses Caprine arthritis-encephalitis virus and Visna virus.
      In these viruses a biased nucleotide frequency in the RRE region suggests that
      selection for the RRE RNA secondary structure affects the amino acid sequence of
      the env gene. Our results show a variation in the ruggedness of fitness
      landscapes which are based on a high degree of epistatic interactions. Fitness
      landscapes play an essential role, not only in biotic evolution, but also in all
      kinds of optimization processes (Hill Climbing, Simulated Annealing, Genetic
      Algorithms, etc). Variation in their ruggedness should therefore be taken into
      account in the analysis of these processes.

PMID- 7507188
TI  - Characterization of mutants of human immunodeficiency virus type 1 that have
      escaped neutralization by a monoclonal antibody to the gp120 V2 loop.
AB  - The biologically cloned human immunodeficiency virus type 1 (HIV-1) RF isolate is
      sensitive to neutralization by the murine monoclonal antibody (MAb) G3-4 to a
      conformationally sensitive epitope in the V2 loop of HIV-1 gp120. To assess how
      variation in the V2 amino acid sequence affects neutralization by this MAb, we
      cultured RF in the presence of G3-4 to select neutralization escape mutants.
      Three such mutants resistant to G3-4 neutralization were generated from three
      independent experiments. Solubilized gp120 from each of these escape mutants had
      a reduced affinity for G3-4 and also for two other V2 MAbs that were able to bind
      the wild-type RF gp120. PCR sequencing of the entire gp120 of the wild-type RF
      virus and the escape mutants showed that amino acid substitutions had occurred
      only at two positions, Y177H and L179P, both in V2. Experimental introduction of
      the Y177H substitution into the RF V2 loop in the context of the NL4-3 molecular
      clone re-created the G3-4-resistant phenotype. The L179P mutant was not viable.
      Thus, our findings confirm that the HIV-1 V2 loop contains the conformationally
      sensitive neutralization epitope recognized by G3-4 and that a single amino acid
      substitution within this region can result in escape variants that arise from
      immune selection pressure.

PMID- 7507190
TI  - CD14 mediated endogenous TNF-alpha release in HL60 AML cells: a potential model
      for CD14 mediated endogenous cytokine release in the treatment of AML.
AB  - In previous studies, HL60 AML cells treated with tumor necrosis factor-alpha
      (TNF), interferon-gamma (IFN), and lipopolysaccharides (LPS) displayed decreased
      growth and viability, enhanced monocytic pathway differentiation and endogenous
      TNF release. Endogenous TNF release by LPS/TNF/IFN treated HL60 cells was
      postulated to play a role with the above findings. In these studies, HL60 cells
      expressed CD14 when treated with TNF, IFN, and LPS. CD14 mediates TNF release in
      monocytes/macrophages in response to binding of LPS with LPS binding protein
      (LBP). CD14 was not expressed in either untreated or LPS only treated HL60 cells.
      CD14 expression was present and greater with HL60 cells cultured with LPS/TNF/IFN
      vs TNF/IFN (47.47% vs 9.07% positive, respectively) suggesting synergism for LPS
      in CD14 induction. CD14 expression was associated with endogenous TNF release,
      and with significantly higher levels by HL60 cells treated with LPS/TNF/IFN vs
      TNF/IFN (p < 0.001). Addition of anti-CD14 antibody significantly reduced release
      of TNF in TNF/IFN (p < 0.001) and LPS/TNF/IFN (p = 0.0013) treated cells. KG1 and
      U937 AML cells treated with LPS, TNF, and IFN did not express CD14, nor release
      TNF. A model for inducing release of endogenous growth inhibitory cytokines by
      CD14 bearing AML cells is proposed as an approach to AML therapy.

PMID- 7507191
TI  - Synergy between SCF or M-CSF with IL-3 or GM-CSF in FDC-P1 cells: a sensitive
      assay of transforming mutations of c-fms.
AB  - Stem cell factor (SCF) was found to stimulate the growth of the haemopoietic cell
      line FDC-P1 in synergy with either interleukin 3 (IL-3) or granulocyte-macrophage
      colony stimulating factor (GM-CSF). Similarly, macrophage colony-stimulating
      factor (M-CSF) was shown to synergize with IL-3 or GM-CSF, following the
      infection of FDC-P1 cells with a recombinant retrovirus which encoded the
      receptor for M-CSF (M-CSFr). These results raise the possibility that signal
      transduction pathways which are controlled by SCF in FDC-P1 cells, can be
      activated by M-CSF if its receptor is illicitly expressed. FDC-P1 cells that
      expressed the M-CSFr were responsive to as little as 100 U/ml of M-CSF when added
      in combination with IL-3 or GM-CSF. This sensitive assay was used to demonstrate
      that transforming deletions of the C-terminal tail of the M-CSFr and two-point
      mutations within the same region that converted tyrosine 969 to either
      phenylalanine or to cysteine, allowed the mutant M-CSF receptors to synergize
      with IL-3 or GM-CSF in the absence of M-CSF. These mutations were found to be
      more evidently transforming in FDC-P1 cells than in Rat-2 fibroblasts. The
      possible relevance of these results to leukaemia and to gynaecological
      malignancies is discussed.

PMID- 7507192
TI  - Idarubicin-containing regimen and G-CSF are capable of recruiting CD34+/DR- cells
      with high proliferative potential which sustain Ph-negative polyclonal
      hematopoiesis.

PMID- 7507193
TI  - Detection of AML1/ETO fusion transcript as a tool for diagnosing t(8;21) positive
      acute myelogenous leukemia.
AB  - The nonrandom chromosomal translocation t(8;21)(q22;q22) can be found frequently
      in acute myelogenous leukemia with maturation (AML-M2). The breakpoint of this
      translocation has been cloned and characterized, and fusion transcript AML1/ETO
      has been identified. Reverse transcription polymerase chain reaction (RT-PCR) can
      be used to amplify the breakpoint site of AML1/ETO in t(8;21)-positive AML-M2
      patients. The chimeric transcript can be detected in all 16 (100%) t(8;21)
      positive AML-M2 patients. In all samples, the size of the amplified DNA fragments
      and pattern of restriction digest were identical, indicating that the t(8;21)
      translocation breakpoint occurs within a single intron of the AML1 and ETO genes.
      Interestingly, this fusion transcript was also detected in one of 13 AML-M2
      patients without the t(8;21) translocation, indicating that a masked
      translocation involving chromosomes 8 and 21, exists in AML. Minimal residual
      disease was detected by semi-nested RT-PCR in all four patients tested, who had
      been in complete remission for 12, 15, 34, and 52 months, respectively. These
      results indicate that RT-PCR amplification of the AML1/ETO fusion transcript is a
      powerful tool for diagnosing and monitoring minimal residual disease in AML-M2
      patients.

PMID- 7507194
TI  - [Nitric oxide and sepsis].

PMID- 7507195
TI  - Regulation with RANTES.

PMID- 7507197
TI  - Modulation of contractile proteins in embryonic and fetal chick cardiac cells by
      phorbol ester, gamma-interferon, 5-azacytidine and diacylglycerols.
AB  - We studied changes in the concentration of tropomyosin, actin, desmin and
      vimentin in cultured myocardiocytes from Hamburger and Hamilton's stages 29 and
      39 chick embryos (HH29 and HH39) (1), treated with 12-o-tetradecanoyl-phorbol-13
      acetate (TPA), 5-azacytidine (AZA), gamma interferon (INF) and diacylglycerols
      (DAG). In embryonic myocardiocytes at HH29, the first three agents modified the
      intracellular distribution of the thin filament proteins tropomyosin and actin,
      increasing their cytoplasmic concentration and decreasing their cytoskeletal
      concentration. The concentration of the intermediate filament proteins desmin and
      vimentin increased in both subcellular fractions after treatment with these
      drugs. In fetal myocardiocytes at HH39, total protein content decreased after
      treatment with these drugs. Cytoplasmic and cytoskeletal concentrations of actin
      and tropomyosin decreased to different degrees after treatment with TPA, AZA or
      DAG in HH39 myocardiocytes. TPA, AZA and DAG decreased desmin in the cytoplasmic
      and cytoskeletal fractions. These findings suggest that the drugs tested alter
      the normal protein composition in cultured myocardiocytes, and have different
      effects depending on the developmental stage in which the embryo is treated.

PMID- 7507196
TI  - RANTES chemokine expression in cell-mediated transplant rejection of the kidney.
AB  - RANTES (regulated upon activation, normal T cell expressed and secreted) is a
      chemotactic cytokine (a chemokine) for memory T lymphocytes, monocytes, and
      eosinophils. RANTES expression was studied in renal allograft biopsy specimens.
      Although RANTES was not expressed in samples taken one hour after
      transplantation, or in native renal biopsy specimens from patients with
      cyclosporin nephrotoxicity, it was expressed during cell-mediated transplant
      rejection. RANTES mRNA was detected in infiltrating mononuclear cells and renal
      tubular epithelium, and RANTES protein was localised to mononuclear cells,
      tubular epithelium, and vascular endothelium. This suggests RANTES has a role in
      allograft rejection.

PMID- 7507199
TI  - Neutralization of Chlamydia psittaci with monoclonal antibodies.
AB  - Neutralization of Chlamydia (C.) psittaci avian strain P-1041 was examined in
      vitro using monoclonal antibodies (MAbs). Of the 10 MAbs used, 6 were found to
      exhibit neutralizing capability. These include 3 against major outer membrane
      protein (MOMP), 1 against lipopolysaccharide (LPS) and 2 against other protein
      molecules [90 kilodalton (kDa) and 90/50 kDa]. Most neutralizing MAbs were
      dependent on complement for efficient neutralization, while a strain-specific MAb
      (2B5) against the 90 kDa protein displayed a different requirement for complement
      and neutralized the infectivity of the P-1041 at high concentrations without
      complement. By competitive inhibition enzyme-linked immunosorbent assay
      (competitive inhibition ELISA), all 3 neutralizing anti-MOMP MAbs were
      demonstrated to recognize different epitopes found in very close proximity to
      each other on the outer membrane.

PMID- 7507200
TI  - Japanese patients with chronic fatigue syndrome are negative for known retrovirus
      infections.
AB  - Although chronic fatigue syndrome (CFS) is known to be the syndrome that begins
      with an acute flu-like illness that may be due to the exposure to an infectious
      agent, there has been no convincing evidence on the causative agents. Recently,
      human T-lymphotropic virus type II (HTLV-II)-like virus has been reported to be
      associated with the CFS by using HTLV Western blot analysis and polymerase chain
      reaction. However, some investigators could not detect HTLV-II by indirect
      immunofluorescence analysis. Lately, CFS patients have been reported in Japan. We
      detected all 30 tested patients with CFS were seronegative for HTLV-II, HTLV-I
      and HIV by specific peptide ELISA and Western blot. Further, PCR analysis was
      negative for HTLV-II and retrovirus was not detected by coculture method with
      patients' PBMC. Thus, known human retrovirus infections do not cause a CFS in
      Japan.

PMID- 7507198
TI  - Effect of metyrapone on tryptophan binding to rat hepatic nuclei.
AB  - This study evaluated whether metyrapone (2-methyl-1,2-di-3-pyridyl-1-propanone),
      an inhibitor of endogenous adrenal corticosteroid synthesis via inhibition of
      cytochrome P-450-mediated steroid hydroxylation, would influence the binding of L
      tryptophan to rat hepatic nuclei or nuclear envelopes. Previous publications have
      indicated that binding of L-tryptophan to hepatic nuclear envelope proteins was
      saturable, stereospecific, and of high affinity. In this study, we investigated
      whether metyrapone would influence L-tryptophan binding to rat hepatic nuclei or
      nuclear envelopes as assayed by in vitro L-(5-3H)tryptophan binding. Our results
      indicate that the addition of metyrapone in vitro has little influence on L-(5
      3H)tryptophan binding to hepatic nuclei or nuclear envelopes. On the other hand,
      when metyrapone (1 mg/100 g body weight) is tube-fed 30 minutes before killing,
      the isolated hepatic nuclei show decreased specific L-tryptophan binding (total
      binding minus nonspecific binding [using 2,000-fold excess of unlabeled L
      tryptophan]) compared with controls. Also, addition of metyrapone in vitro to rat
      liver before homogenization and preparation of nuclei caused the nuclei to show
      decreased specific tryptophan binding compared with controls. Under these in
      vitro conditions, SKF 525A, another inhibitor of hydroxylation, showed inhibitory
      effects similar to those of metyrapone. Thus, metyrapone can interfere with rat
      liver nuclear envelope receptor binding to L-tryptophan, and possibly acts via
      its effects on hydroxylation. At high doses, metyrapone (20 mg/100 g body weight)
      appears to inhibit tryptophan-induced stimulation of hepatic protein synthesis.

PMID- 7507201
TI  - Single dose aprotinin in routine cardiac surgery.
AB  - Evidence exists that the serine protease inhibitor, aprotinin, when used in high
      dosage, can reduce the bleeding associated with cardiopulmonary bypass. This high
      dosage is particularly effective in patients at increased risk for bleeding. Less
      convincing information is available for regimens that use a lower dose and its
      place in routine cardiac surgery has not been fully resolved. Some studies have
      shown significant benefit from a single dose added to the cardio-pulmonary bypass
      prime and we re-examined this alternative. In a randomized, prospective, double
      blinded study, we compared this single dose method with placebo in a low risk
      adults undergoing a first procedure. Benefit was considered established if a
      significant reduction in blood loss or the use of transfused blood products was
      seen. We found a significant reduction in red cell transfusion but no improvement
      in blood loss or blood component transfusion in the treated group. This included
      patients maintained on aspirin as well as those not receiving aspirin. Aspirin
      significantly increased blood loss in both control and treatment groups and the
      usage of blood products in the treatment group. Aprotinin in this low, single
      dosage was not confirmed as an effective means of improving hemostasis following
      CPB in routine cardiac surgery.

PMID- 7507202
TI  - Activation of phospholipase C-gamma 1 through transfected platelet-derived growth
      factor receptor enhances interleukin 2 production upon antigen stimulation in a T
      cell line.
AB  - Phospholipase C-gamma 1 (PLC gamma 1) plays an important role in the signal
      transduction pathway by producing second messengers. However, the activation
      mechanism of PLC gamma 1 and the role of the phosphatidylinositol pathway for
      interleukin 2 (IL-2) production in T lymphocytes remain to be determined. To
      analyze the functional role of this pathway in T cells, we expressed an epidermal
      growth factor receptor (EGF) or platelet-derived growth factor (PDGF) receptor
      (EGF-R or PDGF-R), both of which are known to directly activate PLC gamma 1 in
      fibroblasts, into a murine T-cell hybridoma. Both receptors were expressed on the
      cell surface and caused tyrosine phosphorylation of multiple substrates,
      including the receptor itself, upon ligand binding. While EGF stimulation did not
      either cause phosphorylation of PLC gamma 1 or induce Ca2+ mobilization in the
      EGF-R transfectant in this system, PDGF treatment induced tyrosine
      phosphorylation of PLC gamma 1 and Ca2+ mobilization in the PDGF-R transfectant.
      Stimulation through PDGF-R enhanced IL-2 production upon antigen stimulation of
      the transfectants, although PDGF treatment alone did not induce IL-2 production.
      These results suggest that activation of the phosphatidylinositol pathway affects
      the downstream pathway to IL-2 production but is not sufficient to produce IL-2
      and that cooperation with signals from tyrosine kinase cascades is required for
      IL-2 production.

PMID- 7507203
TI  - Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase by p50csk kinase
      creates a binding site for p56lck tyrosine kinase and activates the phosphatase.
AB  - Src family protein tyrosine kinases (PTKs) play an essential role in antigen
      receptor-initiated lymphocyte activation. Their activity is largely regulated by
      a negative regulatory tyrosine which is a substrate for the activating action of
      the CD45 phosphotyrosine phosphatase (PTPase) or, conversely, the suppressing
      action of the cytosolic p50csk PTK. Here we report that CD45 was phosphorylated
      by p50csk on two tyrosine residues, one of them identified as Tyr-1193. This
      residue was not phosphorylated by T-cell PTKs p56lck and p59fyn. Tyr-1193 was
      phosphorylated in intact T cells, and phosphorylation increased upon treatment
      with PTPase inhibitors, indicating that this tyrosine is a target for a
      constitutively active PTK. Cotransfection of CD45 and csk into COS-1 cells caused
      tyrosine phosphorylation of CD45 in the intact cells. Tyrosine-phosphorylated
      CD45 bound p56lck through the SH2 domain of the kinase. Finally, p50csk-mediated
      phosphorylation of CD45 caused a severalfold increase in its PTPase activity. Our
      results show that direct tyrosine phosphorylation of CD45 can affect its activity
      and association with Src family PTKs and that this phosphorylation could be
      mediated by p50csk. If this is also true in the intact cells, it adds a new
      dimension to the physiological function of p50csk in T lymphocytes.

PMID- 7507204
TI  - Xenopus gamma-crystallin gene expression: evidence that the gamma-crystallin gene
      family is transcribed in lens and nonlens tissues.
AB  - Crystallins, the major gene products of the lens, accumulate to high levels
      during the differentiation of the vertebrate lens. Although crystallins were
      traditionally thought to be lens specific, it has recently been shown that some
      are also expressed at very low levels in nonlens tissues. We have examined the
      embryonic expression pattern of gamma-crystallins, the most abundant crystallins
      of the embryonic lens in Xenopus laevis. The expression profile of five Xenopus
      gamma-crystallin genes mirrors the pattern of lens differentiation in X. laevis,
      exhibiting on average a 100-fold increase between tailbud and tadpole stages.
      Four of these genes are also ubiquitously expressed outside the lens at a very
      low level, the first demonstration of nonlens expression of any gamma-crystallin
      gene; expression of the remaining gene was not detected outside the head region,
      thus suggesting that there may be two classes of gamma-crystallin genes in X.
      laevis. Predictions regarding control mechanisms responsible for this dual mode
      of expression are discussed. This study raises the question of whether any
      crystallin, on stringent examination, will be found exclusively in the lens.

PMID- 7507205
TI  - A factor induced by differentiation signals in cells of the macrophage lineage
      binds to the gamma interferon activation site.
AB  - Rapid transcriptional induction of genes in response to gamma interferon (IFN
      gamma) is mediated by the IFN-gamma activation site (GAS) and its cognate
      protein, the IFN-gamma activation factor (GAF). We describe a GAS-associated,
      differentiation-induced factor (DIF) as a potential molecular link between the
      activities of IFN-gamma and of growth and differentiation factors. DIF DNA
      binding was activated by colony-stimulating factor 1 in murine macrophages and
      also during tetradecanoyl phorbol acetate-induced differentiation or IFN-gamma
      treatment in myeloid U937 cells. IFN-gamma activation of DIF decreased
      significantly upon monocytic differentiation. DIF binding to DNA was inhibited by
      antiphosphotyrosine antibodies and could be induced by treatment of U937 cells
      with vanadate. Unlike GAF, DIF-DNA complexes did not contain the 91-kDa protein
      (p91) from ISGF-3. DIF bound with high affinity to GAS from the promoters of the
      IFP 53/tryptophanyl-tRNA synthetase and Fc gamma RI genes, intermediate affinity
      to the Ly6A/E GAS, and low affinity to the guanylate-binding protein GAS. DIF may
      belong to a family of cytokine- or growth factor-induced factors binding with
      variable affinities to GAS-related elements: the interleukin-6-responsive acute
      phase response factor associated with GAS from different IFN-inducible promoters
      but with a different preference of binding compared with DIF. The sis-inducible
      element of the c-fos promoter bound GAF but not DIF. However, the sis-inducible
      element could be changed by point mutation to compete for GAF and DIF binding.
      Our data show DIF to be a novel DNA-binding protein which is activated in
      response to differentiating signals. Moreover, they suggest that a family of
      cytokine- or growth factor-regulated proteins integrates and coordinates the
      responses to cytokines and to growth and differentiation factors by binding to
      GAS-related elements.

PMID- 7507206
TI  - ATBF1, a multiple-homeodomain zinc finger protein, selectively down-regulates AT
      rich elements of the human alpha-fetoprotein gene.
AB  - ATBF1 is a 306-kDa protein containing four homeodomains, 17 zinc finger motifs,
      and several segments potentially involved in transcriptional regulation (T.
      Morinaga, H. Yasuda, T. Hashimoto, K. Higashio, and T. Tamaoki, Mol. Cell. Biol.
      11:6041-6049, 1991). At least one of the homeodomains of ATBF1 binds to an AT
      rich element in the human alpha-fetoprotein (AFP) enhancer (enhancer AT motif).
      In the present work, we analyzed the transcriptional regulatory activity of ATBF1
      with respect to the enhancer AT motif and similar AT-rich elements in the human
      AFP promoter and the human albumin promoter and enhancer. Gel retardation assays
      showed that ATBF1 binds to the AFP enhancer AT motif efficiently; however, it
      binds weakly or not at all to other AT-rich elements in the AFP and albumin
      regulatory regions studied. Alterations of the enhancer AT motif by site-specific
      mutagenesis resulted in the loss of binding of ATBF1. Cotransfection experiments
      with an ATBF1 expression plasmid and the chloramphenicol acetyltransferase (CAT)
      gene fused to AFP promoter or enhancer fragments showed that ATBF1 suppressed the
      activity of AFP enhancer and promoter regions containing AT-rich elements. This
      suppression was reduced when the mutated AT motifs with low affinity to ATBF1
      were linked to the CAT gene. The ATBF1 suppression of AFP promoter and enhancer
      activities appeared to be due, at least in part, to competition between ATBF1 and
      HNF1 for the same binding site. In contrast to the AFP promoter and enhancer, the
      albumin promoter and enhancer were not affected by ATBF1, although they contain
      homologous AT-rich elements. These results show that ATBF1 is able to distinguish
      AFP and albumin AT-rich elements, leading to selective suppression of the AFP
      promoter and enhancer activities.

PMID- 7507208
TI  - Prokaryotic expression cloning of a novel human tyrosine kinase.
AB  - Screening of a human embryonic lung fibroblast cDNA expression library with
      antiphosphotyrosine antibodies led to isolation of a novel protein kinase. A
      clone, designated A6, contained a 3-kb cDNA insert with a predicted open reading
      frame of 350 amino acids. DNA sequence analysis failed to reveal any detectable
      similarity with previously known genes, and the predicted A6 protein lacked any
      of the motifs commonly conserved in the catalytic domains of protein kinases.
      However, the bacterially expressed beta-galactosidase-A6 fusion protein
      demonstrated both tyrosine and serine phosphorylation in an in vitro kinase assay
      and phosphorylated exogenous substrates including myelin basic protein
      specifically on tyrosine residues. The enzyme also displayed biochemical
      properties analogous to those of other protein tyrosine kinases. The A6 gene was
      found to be expressed widely at the transcript level in normal tissues and was
      evolutionarily conserved. Thus, A6 represents a novel tyrosine kinase which is
      highly divergent from previously described members of this important class of
      regulatory molecules.

PMID- 7507207
TI  - Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and
      IRF-2 genes: implications for a gene network in the interferon system.
AB  - Interferon regulatory factor 1 (IRF-1) and IRF-2 are structurally similar DNA
      binding factors which were originally identified as regulators of the type I
      interferon (IFN) system; the former functions as a transcriptional activator, and
      the latter represses IRF-1 function by competing for the same cis elements. More
      recent studies have revealed new roles of the two factors in the regulation of
      cell growth; IRF-1 and IRF-2 manifest antioncogenic and oncogenic activities,
      respectively. In this study, we determined the structures and chromosomal
      locations of the human IRF-1 and IRF-2 genes and further characterized the
      promoters of the respective genes. Comparison of exon-intron organization of the
      two genes revealed a common evolutionary structure, notably within the exons
      encoding the N-terminal portions of the two factors. We confirmed the chromosomal
      mapping of the human IRF-1 gene to 5q31.1 and newly assigned the IRF-2 gene to
      4q35.1, using fluorescence in situ hybridization. The 5' regulatory regions of
      both genes contain highly GC-rich sequences and consensus binding sequences for
      several known transcription factors, including NF-kappa B. Interestingly, one IRF
      binding site was found within the IRF-2 promoter, and expression of the IRF-2
      gene was affected by both transient and stable IRF-1 expression. In addition, one
      potential IFN-gamma-activated sequence was found within the IRF-1 promoter. Thus,
      these results may shed light on the complex gene network involved in regulation
      of the IFN system.

PMID- 7507211
TI  - Micronuclei and 3AB index in human and canine lymphocytes after in vitro X
      irradiation.
AB  - The comparative study of different species could be of interest, both applied and
      pure, to the field of cytogenetic damage induced by genotoxic agents. For as
      accurate as possible an evaluation of the inter-species response differences to
      radiation, we have carried out a comparison between the behaviors of human and
      canine lymphocytes, using the micronucleus assay (MN test) according to the
      cytokinesis-block method. Up to 4 Gy doses, canine lymphocytes have been found to
      be about three times more radiosensitive than human lymphocytes, due to
      blastization inhibition (binucleation failure), and, for 1 and 2 Gy doses, about
      1.3 times more radiosensitive, due to MN yields. We discuss whether the differing
      chromosome number (dog 78 and man 46) could have any effect on the cytogenetic
      response. 3-Aminobenzamide, which inhibits poly(ADP-ribose)polymerase activity,
      is able to increase the genotoxic effect of X-rays in human lymphocytes, with a
      different response at the individual level. The same phenomenon with the same
      characteristics is also found in canine lymphocytes at the inter-individual
      level. Our in vitro radiobiological study confirms that the cytogenetic response
      obtained in blood from selected breeds of mammalian species can be utilized for
      applications in environmental studies.

PMID- 7507212
TI  - Evaluation of the Allium anaphase-telophase test in relation to genotoxicity
      screening of industrial wastewater.
AB  - The Allium anaphase-telophase test was evaluated to find out if it could be
      recommended in the screening of wastewater for genotoxicity. Five mutagenic or
      carcinogenic chemicals usually found in wastewater were tested in the Allium
      anaphase-telophase test. Sodium dichromate (25 microM), benzene (100 microM),
      dichloromethane (175 microM) and 1,1,1-trichloromethane (175 microM) increased
      the frequency of chromosome aberrations in the root cells, whereas formaldehyde
      (1 mM) was found to be non-mutagenic in this test system. Other studies where
      chemicals were tested in the Allium test were reviewed. For 15 chemicals the
      results were compared with results from the Ames test, the Microscreen assay, and
      carcinogenicity tests in rodents. The sensitivity of the Allium test was
      calculated to be 82%. In conclusion the Allium test is recommended for the
      screening of wastewater because it has a high sensitivity, is cheap, rapid, easy
      to handle, and because it can be used on wastewater without pretreatment of the
      sample.

PMID- 7507209
TI  - Induction of the DNA-binding activity of c-jun/c-fos heterodimers by the
      hepatitis B virus transactivator pX.
AB  - The hepatitis B virus (HBV) X protein (pX) is capable of activating transcription
      regulated by viral and cellular promoters containing binding sites for different
      transcription factors, including AP1. In this study we have analyzed the
      mechanisms of AP1 induction by pX. The hepatitis B virus transactivator was able
      to activate TRE (12-O-tetradecanoylphorbol-13-acetate response element)-directed
      transcription in different cell lines, including HepG2, HeLa, CV1, and PLC/PRF/5
      cells. pX-induced AP1 activation in HepG2 cells was associated with an increase
      in the DNA-binding activity of c-Jun/c-Fos heterodimers, which was not dependent
      either on an increase in the overall amount of c-Fos and c-Jun proteins in the
      cells or on formation of dimers between pX and the two proteins, thus suggesting
      the involvement of posttranslational modifications of the transcription factor.
      The observation that the overexpression of c-Jun and c-Fos in the cells results
      in a strong augmentation of the effect of pX on TRE-directed transcription is
      additional evidence indicating the involvement of posttranscriptional
      modifications of c-Jun/c-Fos heterodimers. The increased AP1 binding observed in
      the presence of pX was unaffected by the protein kinase C inhibitors calphostin C
      and sphingosine and by the protein kinase A inhibitor HA1004, while it was almost
      completely blocked by staurosporine, a potent and nonspecific protein kinase
      inhibitor, suggesting that protein kinase C- and A-independent phosphorylation
      events might play a role in the phenomenon. The ability of pX also to increase
      TRE-directed transcription in cell lines in which AP1-binding activity is not
      increased (i.e., HeLa, CV1, and PLC/PRF/5 cells) suggests that pX can activate
      canonical TRE sites by different mechanisms as well.

PMID- 7507210
TI  - Endothelial-cell-specific regulation of von Willebrand factor gene expression.
AB  - In both tissue sections and cell culture, the endothelial nature of a cell is
      most commonly determined by demonstration of its expression of von Willebrand
      factor (vWf) protein and/or mRNA. Thus, the mechanism of cell-type-specific
      transcriptional regulation of the vWf gene is central to studying the basis of
      endothelial-cell-specific gene expression. In this study, deletion analyses were
      carried out to identify the region of the vWf gene which regulates its
      endothelial-cell-specific expression. A 734-bp fragment which spans the sequence
      from -487 to +247 relative to the transcription start site was identified as the
      cell-type-specific promoter. It consists of a minimal core promoter located
      between -90 and +22, a strong negative regulatory element located upstream of the
      core promoter (ca. -500 to -300), and a positive regulatory region located
      downstream of the core promoter in the first exon. The activity of the core
      promoter is not cell type specific, and the negative regulatory region is
      required to inhibit its activity in all cell types. The positive regulatory
      region relieves this inhibition only in endothelial cells and results in
      endothelial-cell-specific gene expression. The positive regulatory region
      contains sequences predicting possible SP1, GATA, and octamer binding sites.
      Mutations in either the SP1 or octamer sequence have no effect on transcriptional
      activity, while mutation in the GATA binding element totally abolishes the
      promoter activity. Evidence that a GATA factor is involved in this interaction is
      presented. Thus, the positive regulatory region with an intact GATA binding site
      is required to overcome the inhibitory effect of the negative regulatory element
      and activate vWf gene expression in an endothelial-cell-specific manner.

PMID- 7507214
TI  - Sister-chromatid exchange (SCE) and cell proliferation in lymphocytes from
      infected and non-infected children with severe protein calorie malnutrition
      (PCM).
AB  - The frequency of sister-chromatid exchanges (SCE) and the rate of cell
      proliferation were evaluated through differential staining of sister chromatids
      in mitogen-stimulated cultured lymphocytes sampled from five well-nourished
      children, from seven severely malnourished children infected with bacterium, and
      from 10 severely malnourished children following treatment for infection with
      antimicrobial drugs 2 weeks before blood sampling. The replication indices at 48
      h of culture were higher in both groups of malnourished children than in the well
      nourished children, indicating either a faster response to PHA and/or a shorter
      cell cycle in lymphocytes of these patients. The average frequency of SCE per
      mitosis was also significantly higher than in the control group. The mitotic
      index was similar in the three groups of children. The lack of significant
      difference in response between the two groups of malnourished children suggests
      that the effects observed at the cytogenetic level are caused by severe
      malnutrition per se, and not by any associated infection.

PMID- 7507213
TI  - Activation of 4-nitro-o-phenylenediamine by the S2 fraction of Zea mays to
      mutagenic product(s).
AB  - Studies on plant metabolic activation with the S2 fraction from Zea mays have
      been developed. The 4-nitro-o-phenylenediamine (NOP) activation by S2 has been
      analyzed with the Ames test as a short-term assay. The NOP mutagenic potency was
      increased two-fold by S2, while rat liver S9 produced the contrary effect. The
      presence of a NADPH-generating system and the treatment of S2 with CO do not
      modify S2 activation of NOP. In this fraction, neither cytochrome P450 nor some
      enzymatic activities depending on cyt-P450 (aniline hydroxylase and aminopyrine
      demethylase) were detected. Therefore, the enhancement of NOP mutagenic potency
      by S2 is independent of the mixed-function oxidase system. On the other hand,
      inhibitors of the peroxidase activity such as N-acetyl-p-aminophenol caused a
      partial inhibition of S2 activation of NOP. Likewise, diethyldithiocarbamate
      produced both a reduction of the S2 peroxidase activity in biochemical assays and
      a partial inhibition of S2 activation of NOP. Moreover, it was possible to find a
      direct correlation between the activity of peroxidase per plate of both the S2
      fraction and horseradish peroxidase and the number of revertants induced by NOP
      in the TA98 strain. On the basis of these results, we report that a HRP-like
      peroxidase activity must be the main pathway of NOP activation by the plant
      metabolic activation system studied in this work.

PMID- 7507215
TI  - Measurement and characterization of micronuclei in exfoliated human cells by
      fluorescence in situ hybridization with a centromeric probe.
AB  - The micronucleus (MN) assay in human exfoliated cells has been widely used to
      detect the genotoxic effects of environmental mutagens, infectious agents and
      hereditary diseases. Substantial variability characterizes the MN frequencies
      reported by different research groups. One reason for this may be the restricted
      resolution power of the Feulgen-Fast-Green staining that is routinely used. Here
      we describe a new version of the MN assay that employs fluorescent propidium
      iodide staining along with fluorescence in situ hybridization (FISH) with a
      centromeric probe. Buccal and urothelial cells were collected from 5 healthy
      unexposed female volunteers and 55,000 cells analyzed for MN frequency and
      abnormal nuclear events. The Feulgen-Fast-Green and the new fluorescent staining
      produced very similar results. The frequency of MN in buccal cells was 0.145 +/-
      0.118% and in urothelial cells 0.083 +/- 0.074%. No correlation was found between
      the frequencies of MN in the two types of exfoliated cells. FISH with a
      centromeric probe allowed MN containing whole chromosomes with a centromere to be
      differentiated from those containing only acentric fragments. The former appear
      as a result of chromosome lagging in mitosis, while those without a centromere
      are due to chromosome breakage. In urothelial cells 43% of MN were centromere
      negative and in buccal cells -44%. Fluorescent staining provided more accurate
      scoring of degenerative cells than standard Feulgen-Fast-Green staining. The
      combined frequency of pycnotic cells, "broken eggs" and cells with fragmented
      nuclei did not exceed 2%, while that of karyorrhexis and karyolysis together was
      as high as 21%. Significant interindividual variability was found in the
      frequency of cells with karyolysis and karyorrhexis. Thus, the new version of
      micronucleus assay allows for MN to be scored more precisely, the mechanism of MN
      formation to be determined and abnormal nuclear events to be readily identified
      in exfoliated human cells. It is therefore ideal for studying genotoxicity in
      human populations using exfoliated cells from the mouth, bladder and nose.

PMID- 7507216
TI  - FISH "painting" patterns resulting from complex exchanges.
AB  - Many of the unusual patterns seen when irradiated chromosomes are FISH painted
      arise from Complex interchanges. In this paper, we present a method for
      classifying chromosome-type complex exchanges. Every possible exchange
      configuration for the first nine complex families has been determined, and for
      each of these, the expected metaphase pattern forms seen if any one of the
      participating chromosomes is painted, has been worked out. A total of 65
      recognisably different pattern forms emerge, and a simple classification of these
      is provided for scoring and discussion purposes. 47 of these patterns are unique
      ("Tell-tale"), in that they are found in, and are diagnostic for, only one
      complex family or sub-family (of the sub-set analyzed). Analysis of the
      contingency tables indicates that: (a) The same individual complex exchange can
      appear in different pattern forms, depending upon which of the participating
      chromosomes is painted, and the converse-different forms can represent the same
      exchange. (b) Many different complex exchange configurations, from different
      families, can give rise to identical pattern forms. (c) If obvious complex forms
      are at all frequent in a sample, then a lot of the exchanges being scored as
      "simple" are not. These observations will have considerable repercussions on the
      numerical assessment of damage when using painted chromosomes at higher radiation
      doses.

PMID- 7507217
TI  - The Pan African Environmental Mutagen Society, report on inaugural meeting:
      "Mycotoxins as mutagens and carcinogens: possibilities for disease prevention",
      Cairo, Egypt, 23-26 January 1993.

PMID- 7507218
TI  - Bone marrow clastogenicity of trimethyltin.
AB  - Aqueous solutions of trimethyltin in four different concentrations were
      administered i.p. for three different treatment periods, to five Swiss albino
      male mice for each experimental set. Bone marrow cells were processed for somatic
      chromosome preparation after 6, 18 and 24 h following the usual protocol.
      Structural abnormalities including chromatid and chromosome breaks, dicentrics,
      rings and fragments were recorded. Critical assessment of the data with the one
      tailed trend test revealed a significant positive trend of the dose effects in
      all three treatment periods. With the ANOVA test, significant variations in
      aberrations were observed between chemical concentrations and between treatment
      periods and their interaction (dose x time) was significant in aberrations and
      mitotic indices. Depression of mitotic index was dose- and duration-dependent.

PMID- 7507219
TI  - The infant or young child with developmental delay.
AB  - The practitioner should attempt to identify the infant and young child with
      developmental delay as early as possible, so that appropriate services can be
      provided. Ongoing surveillance is required, rather than one-time screening. The
      practitioner should also serve as an advocate for children with developmental
      delay. He or she should ensure that appropriate services exist within the child's
      community and that they are readily accessible. This requires ongoing
      communication not only with the child and the family, but also with schools and
      community agencies.

PMID- 7507220
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 7-1994. A 55-year-old heart-transplant recipient with a tender,
      enlarged prostate gland.

PMID- 7507221
TI  - Nitric oxide as a mediator of neurotoxicity.

PMID- 7507222
TI  - Modulation of protectin (CD59 antigen) cell surface expression on human
      neoplastic cell lines.
AB  - The ability of cytokines (IFN alpha, IFN gamma, TNF alpha, IL-1 alpha, IL-6), all
      trans retinoic acid, 1,25(OH)2-vitamin D3 and the tumor promoting phorbol ester
      TPA to regulate cell surface expression of protectin (CD59 antigen) on human
      hematopoietic and non-hematopoietic neoplastic cell lines was examined with the
      aid of immunocytofluorometric measurements. The tumor promoting phorbol ester TPA
      induced a marked up-regulation of protectin in all examined cell lines with the
      exception of promyelocytic leukemia HL-60, where TPA significantly decreased
      protectin cell surface expression. All-trans retinoic acid weakly down-regulated
      cell surface protectin on K-562, while 1,25(OH)2-vitamin D3 produced such effect
      on HL-60 cells. None of the examined cytokines induced a significant protectin
      down-regulation in the examined cell lines.

PMID- 7507223
TI  - Contribution of radiotherapy to the management of malignant melanoma. A ten year
      experience at the University of Illinois Hospital in Chicago.
AB  - Fraction size in radiotherapy of malignant melanoma remains a point of
      controversy. Among 139 patients treated at the University of Illinois Hospital in
      1979-1988, 36 were considered potentially curable (not counting ocular
      melanomas); 20 were treated by the Princess Margaret Hospital (PMH)
      hypofractionated schedule using 800 cGy per fraction and achieved a permanency of
      local control lasting > 6 months since the beginning of radiotherapy in 10/22
      (45.5%) courses. Comparable results were obtained in 11 patients treated by
      standard fractionation to at least threshold curative levels. A modification of
      PMH regimen in 5 patients (but with 13 courses) by decreasing fraction size to
      400 cGy while keeping total dose and course duration unchanged, resulted in a
      100% loss of focal control within 6 months. Patients considered incurable and
      irradiated by PMH schedule responded in 83% of courses compared to 51.4% response
      rate in patients irradiated with other schedules (except modified PMH regimen).
      Other aspects of melanoma management are analyzed.

PMID- 7507224
TI  - Hemoglobin F levels in end-stage renal disease patients after correction of
      anemia with erythropoietin.

PMID- 7507225
TI  - Citrulline-containing myelin basic protein is recognized by T-cell lines derived
      from multiple sclerosis patients and healthy individuals.
AB  - The cause of MS is uncertain, but an autoimmune disorder of the CNS is likely,
      and myelin basic protein (MBP) is a candidate antigen. MBP exists in different
      isoforms, generated by differential splicing of exons, and in charge isomers,
      generated by posttranslational modifications. Different isoforms and charge
      isomers presumably subserve different functions, and they vary in abundance in
      immature myelin found during myelinogenesis and remyelination compared with
      mature myelin. The 18.5-kd isomer is most abundant in normal human adults and
      consequently has been used almost exclusively for immunologic studies in MS. In
      the present study, we examined a different but abundant charge isomer of MBP,
      termed MBP-C8, to determine whether it could be recognized by MBP-specific
      cytotoxic and proliferative T-cell lines (TCL) and whether a T-cell response
      directed exclusively against citrulline-containing residues of MBP-C8 exists in
      MS patients and healthy controls. We showed that citrulline affects antigen
      recognition by some TCL that are specific for areas of MBP that contain the
      citrulline residues. Following stimulation with MBP-C8, MBP-C8-specific TCL could
      be generated from both MS patients and controls. T-cell responses against
      antigens that appear during myelinogenesis and during remyelination may be
      important in inducing and perpetuating an autoimmune response involved in the
      pathogenesis of MS.

PMID- 7507226
TI  - Human papillomavirus 18-immortalized endocervical cells with in vitro cytokeratin
      expression characteristics of adenocarcinoma.
AB  - OBJECTIVE: To determine whether human papillomavirus (HPV) 18 has a role in the
      development of adenocarcinoma from human endo- or ectocervical cells. METHODS:
      Secondary cultures of human endo- and ectocervical cells were assayed for
      immortalization by HPV 18 DNA using lipofection. The effects of immortalization
      on the patterns of cytokeratin expression were determined by indirect
      immunofluorescence using monoclonal antibodies. The differentiation phenotype of
      the immortalized cells was investigated by a modified in vivo implantation
      system. RESULTS: Both endo- and ectocervical cells were immortalized by HPV 18.
      The immortalized cells contained integrated HPV 18 DNA and expressed E6-E7 RNA.
      The immortalized endocervical cells had a cytokeratin phenotype characteristic of
      adenocarcinoma, whereas the immortalized ectocervical cells retained a distinct
      cytokeratin expression pattern of normal parental cells. In an in vivo
      implantation system, endocervical cells formed a lesion resembling severe
      dysplasia or carcinoma in situ, whereas ectocervical cells developed into a
      lesion resembling mild dysplasia. Both cell lines were nontumorigenic in nude
      mice. CONCLUSION: Both endo- and ectocervical cells are targets for
      immortalization by HPV 18. Based on cytokeratin expression patterns, immortalized
      endocervical cells, but not ectocervical cells, may be useful as a model for
      premalignant lesions that progress into adenocarcinoma.

PMID- 7507227
TI  - [Cystectomy in the management of bladder cancer].
AB  - In the course of 20 years 83 patients with tumor of the bladder were treated by
      cystectomy. The infiltrations of the tumors were 14 pT1, 12 pT2, 44 pT3 and 13
      pT4. There were metastatic regional lymph nodes in 11 cases (13%). The urinary
      diversions were 64 ureterosigmoidostomies, 18 ileal conduits and one cutaneous
      ureterostomy. The perioperative complication rate was 48% and mortality rate was
      12%. The 3-year and 5-year survivals were 50% and 44.4%, respectively. Twenty
      three patients (28%) died as a result of cancer recurrence. Parallel with the
      increase in the depth of neoplastic bladder wall infiltrations increases were
      observed in the rates of lymph node metastates and tumorous mortality while a
      decrease of survival was noted. Owing to the observed significant differences in
      survival (3-year survivals 12/23 vs 0/4.5-year survivals 9/20 vs 0/2) and
      tumorous mortality (9/38 vs 4/6) of the T3a and T3b stage patients the authors
      think it has to be justified to separate the two patient groups as regarding
      therapy and prognosis. In T3a cases cystectomy is employed as monotherapy, while
      for T3b cases also adjuvant chemotherapy is recommended. The prognosis of tumors
      extending over the bladder wall is extremely poor. An exception to this in the
      bladder cancer infiltrating the prostate following whose extirpation authors have
      observed more than ten-year survivals in two cases.

PMID- 7507228
TI  - The mouse tie receptor tyrosine kinase gene: expression during embryonic
      angiogenesis.
AB  - Angiogenesis, the process by which new blood vessels are formed, is essential in
      reproduction, development, wound repair and oncogenesis. Endothelial receptor
      tyrosine kinases are likely to play key roles in the intercellular signalling
      controlling angiogenesis. We have here analysed the expression of the endothelial
      receptor tyrosine kinase tie during the earliest stages of vascular development.
      The mouse tie cDNA was isolated and sequenced and the exon structure of the
      coding region was determined. The part of the tie gene encoding the extracellular
      domain was found to be organized in exons specifying the characteristic domains
      of the Tie polypeptide. Early postimplantation mouse tissues were analysed for
      tie expression by in situ hybridization. No tie mRNA was detected in 7.5 day
      mouse embryos. In 8.5 day embryos, tie expression was observed in differentiating
      angioblasts of the head mesenchyme, in the splanchnopleure and dorsal aorta as
      well as in migrating endothelial cells of the developing heart. A weak tie signal
      was also obtained from angioblasts in the blood islands of the yolk sac.
      Furthermore, tie mRNA was prominent in the endocardium of the embryo and in the
      endothelial cells forming the lung vasculature. Expression of tie persisted in
      the lung capillaries of adult mice, but was decreased in the endocardium. These
      results suggest that the tie receptor tyrosine kinase is involved in angiogenesis
      and/or maintenance of endothelial cell functions.

PMID- 7507229
TI  - Activated ras and src induce CD44 overexpression in rat intestinal epithelial
      cells.
AB  - CD44 is an adhesion molecule that is involved in the progression of several tumor
      types, including those originating in the intestine. There are several
      alternatively spliced forms of CD44. Here we show that intestinal epithelial
      cells express the standard form of CD44 (CD44s). The same form of CD44 is found
      in IEC-18, a cell line derived from normal rat intestinal crypts. Upon
      transfection of IEC-18 cells with ras or src, two oncogenes that are frequently
      activated in intestinal tumors, a significant induction of CD44s is observed. A
      causal role for ras in this induction is shown by using IEC clones transfected
      with an inducible ras expression vector. The oncogene-transformed IEC clones
      display a high degree of hyaluronic acid-dependent cell-cell adhesion that is not
      observed in the parental IEC-18 cells suggesting that ras- and src-induced
      overexpression of CD44 can alter the adhesion properties of intestinal cells.

PMID- 7507230
TI  - The EndoA enhancer contains multiple ETS binding site repeats and is regulated by
      ETS proteins.
AB  - EndoA is a type II keratin and with EndoB (type I keratin), constitutes
      intermediate filaments in various simple epithelial tissues. EndoA is
      developmentally regulated and has an enhancer that is located at the 3'- end of
      the gene. This enhancer contains two single and five dual Ets binding sites. Thus
      far, no other promoter or enhancer has been shown to contain as many potential
      clustered Ets binding sites. To study the transcriptional regulation of EndoA by
      the ETS family proteins, we amplified the EndoA enhancer fragment from mouse
      genomic DNA by PCR, and cloned it into the pBLCAT2 vector upstream from the CAT
      reporter gene. Several pBLCAT-ENDOA clones were sequenced to verify the presence
      of all the ETS binding sites. Clones that did not show any point mutations in the
      ETS binding sites were chosen to study the transcription regulation by ETS1, ETS2
      and ERGB/FLI-1 gene products. EMSA results indicated that the ETS1, ETS2 and
      ERGB/FLI-1 proteins bind to the enhancer sequence, and DNase I protection data
      demonstrated that the ETS proteins protect all seven EBS core sequences.
      Cotransfection of the COS cells with the pBLCAT-ENDOA construct, along with
      increasing amounts of different ETS expression vectors, resulted in a significant
      induction of CAT reporter gene expression. Previously, we have shown that the
      overexpression of the ETS1 gene transforms NIH3T3, and these transformed cells
      (7AQS2.1) produce high levels of ETS1 protein (Seth & Papas, 1990). In this
      report, we show that the undifferentiated P19 EC cells do not express detectable
      levels of ETS1; however, an elevated level of ETS1 is expressed in differentiated
      derivatives of these cells. We therefore used these two cell lines to examine the
      activity of the EndoA enhancer with the ETS1 product. Transfection of the pBLCAT
      ENDOA construct alone in undifferentiated P19 EC cells results in very low CAT
      gene expression; however, upon differentiation with retinoic acid the level of
      CAT gene activity increases dramatically. Similarly, an increase in CAT
      expression from the same construct (pBLCAT-ENDOA) was also observed in 7AQS2.1
      cells. Our results therefore indicate that the EndoA enhancer is regulated by ETS
      proteins via interaction with multiple ETS-binding site sequences.

PMID- 7507231
TI  - Scanning the structure and antigenicity of HPV-16 E6 and E7 oncoproteins using
      antipeptide antibodies.
AB  - The structure and antigenicity of the HPV-16 E6 and E7 oncoproteins was studied
      using a set of antisera against overlapping synthetic peptides. We report that
      antigenic, mobile regions of the native proteins, as defined by reactivity with
      antipeptide antisera, occur at the N-termini of both E6 and E7 proteins,
      corresponding to regions of known or suspected protein-protein interactions. The
      putative zinc finger domains were consistently non-reactive, despite computer
      predictions of relatively high antigenicity, suggesting that the proposed zinc
      finger regions are held in stable secondary structures that the peptides were not
      able to mimic. In E6, the linker region between the two zinc fingers was
      antigenic, indicating that the two zinc finger structures might be able to
      articulate relative to one another by a flexible linker region. The highly
      antigenic N-terminal region of HPV-16 E7 was also found to be antigenic in E7 of
      both HPV-11 and HPV-18, indicating that the E7 proteins of different HPV types
      have similar antigenic structures. The identification of antigenic regions of the
      E6 and E7 proteins should be therefore be useful in the design of site-directed
      antibodies against E6 and E7 for numerous HPV types.

PMID- 7507232
TI  - [Peptide growth factors in the prostate].
AB  - Growth and development of the prostate depend on androgen action and other
      factors. Androgens act directly by specific nuclear receptors and induce or
      control many effects mediated by peptide growth factors on both epithelial and
      stromal cells. The major important peptide growth factors detected in the
      prostate are Fibroblast Growth Factors, Transforming Growth Factors, and
      Epidermal Growth Factor. These factors are not prostate specific. They are
      produced by epithelial or stromal cells and regulate the growth of these two cell
      compartments through autocrine or paracrine pathways. Overproduction of these
      factors or modification in affinity or number of cell receptors may participate
      in the two main prostatic pathologies: benign hyperplasia or adenocarcinoma.
      Recently, other factors have been evidenced in the prostate: Interleukine 6,
      Nerve Growth Factor or Insulin-like Growth factors. The study of the localization
      and the effects of these factors may be crucial to understand the prostatic
      development and diseases and may suggest new targets for therapy.

PMID- 7507233
TI  - Two different snoRNAs are encoded in introns of amphibian and human L1 ribosomal
      protein genes.
AB  - We previously reported that the third intron of the X.laevis L1 ribosomal protein
      gene encodes for a snoRNA called U16. Here we show that four different introns of
      the same gene contain another previously uncharacterized snoRNA (U18) which is
      associated with fibrillarin in the nucleolus and which originates by processing
      of the pre-mRNA. The pathway of U18 RNA release from the pre-mRNA is the same as
      the one described for U16: primary endonucleolytic cleavages upstream and
      downstream of the U18 coding region produce a pre-U18 RNA which is subsequently
      trimmed to the mature form. Both the gene organization and processing of U18 are
      conserved in the corresponding genes of X.tropicalis and H.sapiens. The L1 gene
      thus has a composite structure, highly conserved in evolution, in which sequences
      coding for a ribosomal protein are intermingled with sequences coding for two
      different snoRNAs. The nucleolar localization of these different components
      suggests some common function on ribosome biosynthesis.

PMID- 7507234
TI  - Lead-catalyzed cleavage of ribonuclease P RNA as a probe for integrity of
      tertiary structure.
AB  - Pb(2+)-catalyzed cleavage of RNA has been shown previously to be a useful probe
      for tertiary structure. In the present study, Pb2+ cleavage patterns were
      identified for ribonuclease P RNAs from three phylogenetically disparate
      organisms, Escherichia coli, Chromatium vinosum, Bacillus subtilis, and for E.
      coli RNase P RNAs that had been altered by deletions. Each of the native RNAs
      undergoes cleavage at several sites in the core structure that is common to all
      bacterial RNase P RNAs. All the cleavages occur in non-paired regions of the
      secondary structure models of the RNAs, in regions likely to be involved in
      tertiary interactions. Two cleavage sites occur at homologous positions in all
      the native RNAs, regardless of sequence variation, suggesting common tertiary
      structural features. The Pb2+ cleavage sites in four deletion mutants of E. coli
      RNase P RNA differed from the native pattern, indicating alterations in the
      tertiary structures of the mutant RNAs. This conclusion is consistent with
      previously characterized properties of the mutant RNAs. The Pb2+ cleavage assay
      is thus a useful probe to reveal alteration of tertiary structure in RNase P RNA.

PMID- 7507235
TI  - Synthetic RNA-cleaving molecules mimicking ribonuclease A active center. Design
      and cleavage of tRNA transcripts.
AB  - RNA cleaving molecules were synthesized by conjugating imidazole residues
      imitating the essential imidazoles in the active center of pancreatic
      ribonuclease to an intercalating compound, derivative of phenazine capable of
      binding to the double stranded regions of polynucleotides. Action of the
      molecules on tRNA was investigated. It was found, that some of the compounds
      bearing two imidazole residues cleave tRNA under physiological conditions. The
      cleavage reaction shows a bell-shaped pH dependence with a maximum at pH 7.0
      indicating participation of protonated and non-protonated imidazole residues in
      the process. Under the conditions stabilizing the tRNA structure, a tRNAAsp
      transcript was cleaved preferentially at the junctions of the stem and loop
      regions of the cloverleaf tRNA fold, at the five positions C56, C43, C20.1, U13,
      and U8, with a marked preference for C56. This cleavage pattern is consistent
      with a hydrolysis mechanism involving non-covalent binding of the compounds to
      the double-stranded regions of tRNA followed by an attack of the imidazole
      residues at the juxtaposed flexible single-stranded regions of the molecule. The
      compounds provide new probes for the investigation of RNA structure in solution
      and potential reactive groups for antisense oligonucleotide derivatives.

PMID- 7507236
TI  - Control of ColE2 DNA replication: in vitro binding of the antisense RNA to the
      Rep mRNA.
AB  - Expression of the Rep protein of colicin E2 plasmid is negatively controlled at a
      post-transcriptional step by a plasmid-coded RNA (RNAI). RNAI is complementary to
      the 5' nontranslated region of the Rep mRNA and can be folded into two stem-loop
      structures. Several cop mutations that increased the copy number of the plasmid
      have been mapped in the RNAI coding region. Here we demonstrated that RNAI and
      the Rep mRNA rapidly form a stable complex under near physiological conditions.
      The cop mutations drastically reduced the binding rate. The reduction correlated
      to the in vivo phenotypes of the cop mutant plasmids, indicating that binding of
      RNAI to the Rep mRNA is involved in the regulation of the Rep protein expression.
      Binding properties of RNAI and the Rep mRNA with the cop mutations and those with
      various extents of deletion suggested that the initial interaction of the two
      RNAs occurs between the loop portions of the larger of the two stem-loop
      structures. RNAI does not completely sequester the putative S/D region, even when
      the two RNAs form a complete duplex. Possible mechanisms of the inhibition of the
      rep gene expression by binding of RNAI to the Rep mRNA under such a situation
      were discussed.

PMID- 7507237
TI  - Regulation of prostate-specific antigen gene expression in LNCaP human prostatic
      carcinoma cells by growth, dihydrotestosterone, and extracellular matrix.
AB  - We have examined the role of extracellular matrix (ECM), cell growth, and
      dihydrotestosterone on the expression of prostate-specific antigen (PSA) by human
      prostatic carcinoma cells LNCaP. ECM induced a transient decrease in PSA mRNA
      even in the presence of growth factors. PSA mRNA, but not actin mRNA, was down
      regulated on ECM in a biphasic manner and was not detected up to 48 hr after
      culture, but was re-expressed after 3 days. Cycloheximide and actinomycin D
      pretreatment did not prevent ECM-induced down-regulation of PSA mRNA, while
      actinomycin D-treated cells on plastic maintained stable PSA mRNA levels. DNA
      synthesis and PSA glycoprotein secretion were also transiently suppressed on ECM.
      LNCaP growth inhibition correlated with decreased glyceraldehyde phosphate
      dehydrogenase mRNA levels. However, the transient growth suppression induced by
      ECM was not observed with primary endothelial cells on Matrigel. Down-regulation
      of PSA mRNA by culture on Matrigel was reversible upon transfer to a different
      matrix substrate. Re-expression was highest on heparan sulfate proteoglycan (4
      fold) and fibronectin or collagen I (2-fold) compared to plastic or laminin. Our
      results indicate that the morphology and proliferation of LNCaP cells may be
      regulated by the ability of ECM to control cellular differentiation and
      proliferation.

PMID- 7507239
TI  - Age-related changes of the prostate gland in the senescence-accelerated mouse.
AB  - Aging is of utmost importance in the pathogenesis of the prostate gland (i.e.,
      benign prostate hyperplasia or prostatic carcinoma). The object of this study was
      to examine the morphological and histological changes of the aging prostate of
      the so-called senescence-accelerated mouse (SAM). Ventral and dorsolateral lobes
      of prostate glands of SAM were microdissected into two-dimensional ductal arrays.
      Gross morphology, ductal branching patterns, and histology were examined in these
      microdissected specimens. Wet weight and numbers of ductal tips in ventral and
      dorsolateral prostate glands in senescence accelerated-prone (SA-P) mice were
      significantly smaller than those of senescence accelerated-resistant (SA-R) mice,
      although the changes of patterns of gross ductal morphology were virtually
      identical in these groups. High incidence of stromal hyperplasia with fibrosis
      and inflammation was observed in the dorsal lobe of the aged SA-P mouse. Atypical
      glandular epithelial cells and cribriform glandular deformity were observed in
      the dorsal and lateral lobe of aged SA-P mice. Marked heterogeneity in age
      related pathological changes was observed between prostatic lobes. These data
      suggest that the aging process occurs heterogeneously within the prostate gland,
      and that SA-P mice may be an important model for the study of age-related changes
      in the prostate gland.

PMID- 7507240
TI  - First use of G-CSF in chlorpromazine-induced agranulocytosis: a report of two
      cases.
AB  - Chlorpromazine-induced agranulocytosis is an uncommon disorder associated with a
      high frequency of fatality. We describe two patients with chlorpromazine-induced
      granulocytosis in whom granulocyte colony stimulating factor (G-CSF)
      administration enhanced the speed of neutrophil recovery. No toxicity was noted
      with G-CSF and both patients made a successful recovery. We propose there is a
      role for such cytokine therapy in patients with life-threatening agranulocytosis
      in order to speed the recovery of neutrophils.

PMID- 7507238
TI  - Nuclear casein kinase 2 (CK-2) activity in human normal, benign hyperplastic, and
      cancerous prostate.
AB  - In previous work, we had observed that chromatin-associated nonhistone protein
      phosphorylation, catalyzed by intrinsic protein kinase reaction in chromatin
      preparations from human benign prostatic hyperplasia (BPH) prostate samples was
      markedly elevated, compared with the normal prostate chromatin samples [Rayan et
      al: Cancer Res 45:2277-2282, 1985]. The properties of this protein kinase
      reaction were suggestive of the involvement of casein kinase(s). By employing the
      specific synthetic substrate for casein kinase 2 (CK-2) for assays in cellular
      fractions, we have shown that this protein kinase is present in human prostate
      chromatin. Its activity is increased in BPH chromatin by about 25-fold, as
      compared with its activity in the normal prostate chromatin. This suggests that
      CK-2 is a possible mediator of the enhanced phosphorylation of chromosomal
      proteins in BPH chromatin. By comparison, CK-2 activity in chromatin preparations
      from prostatic carcinoma samples was markedly less elevated than that of the BPH
      chromatin. Immunohistochemical analysis of the enzyme in human frozen sections of
      prostate tissue samples showed that the enzyme immunostaining was diffuse in the
      cytoplasm, but more intense in the nucleus, especially in the nucleoli. In
      general, the staining corresponded with the enzymic data. However, sections from
      prostatic carcinoma samples appeared to show differential staining, depending on
      the Gleason's grade of the sample. The samples with higher Gleason's grade showed
      less intense immunostain in the nucleus, compared with samples of lower Gleason's
      grade. Further, regions of sections in samples with higher Gleason's grade did
      not show any immunostaining. These differences in the characteristics of CK-2
      expression in prostatic carcinoma samples may be potentially significant, but
      need to be evaluated further for their significance to the pathobiology of
      prostatic neoplasia.

PMID- 7507241
TI  - Pulmonary absorption of recombinant methionyl human granulocyte colony
      stimulating factor (r-huG-CSF) after intratracheal instillation to the hamster.
AB  - Recombinant methionyl human granulocyte colony stimulating factor (G-CSF), a
      molecule of 18.8 kDa, has been shown to induce a systemic response after delivery
      by aerosol. In this work, rate and extent of absorption as well as the response
      were determined after bolus administration of solutions by intratracheal
      instillation (IT). The protein was quantified using a specific ELISA and the
      biological response was assessed by monitoring the increase in numbers of
      circulating white blood cells (WBC). A dose-response curve was obtained after IT,
      subcutaneous injection (SC), and intracardiac injection (IC) of 100 microL of a
      nominal dose ranging from 1 to 1000 micrograms/kg G-CSF (n = 5). WBC numbers were
      determined 24 hr postadministration. Absorption and clearance kinetics were
      determined after IT and IC of 500 micrograms/kg protein over a 24-hr time period
      (n = 5). The response of the lung to G-CSF was monitored by WBC counts and
      differentials in lung lavage fluid. 73.6 +/- 10.5% (n = 7) of the IT dose reached
      the lung lobes. The response to single doses of G-CSF by IT or SC was similar,
      with WBC numbers increasing over 4x baseline at the higher doses. Absorption from
      the lung was rapid and did not follow first-order kinetics. Clearance after the
      IC dose was described by a biexponential equation (alpha = 1.41, beta = 0.24 hr
      1). Peak serum levels were obtained approximately 1-2 hr after IT. The
      bioavailability was 45.9% of the administered dose and 62.0% of the dose reaching
      the lung lobes. These results indicate that G-CSF is rapidly absorbed from the
      lung.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507242
TI  - Immunohistochemical localization of nitric oxide synthase in the human placenta.
AB  - We have studied the distribution of the endothelial isoform of nitric oxide
      synthase (NOS) through the term human umbilical cord and placenta by
      immunohistochemistry. Histochemistry with the NADPH diaphorase substrate
      nitroblue tetrazolium (NBT) has also been used to establish if other isoforms of
      NOS may be present in these tissues. Positive immunofluorescence for endothelial
      NOS was found in umbilical cord artery and vein endothelium, although positive
      staining was only found in approximately 50% of veins. The endothelium of stem
      villous vessels dissected from beneath the chorionic plate was also intensely
      immunostained. In the terminal villi punctate immunostaining was found at the
      basal aspect and around nuclei of syncytiotrophoblast, but was absent from stroma
      and endothelium of terminal villous vessels. A positive histochemical stain for
      NBT was found in cord artery and vein endothelium and stem villous vessel
      endothelium. Intense diffuse staining with NBT was found in syncytiotrophoblast,
      but no other cell types in the terminal villi stained with NBT. The endothelial
      NOS isoform appears to be localized in the resistance vasculature of the
      placenta, but not in the capillary endothelium of terminal villi where there is
      no underlying smooth muscle. It may contribute to the 'endothelial' function of
      syncytiotrophoblast if secreted towards the intervillous space or alternatively
      fulfil other signal transduction roles. The pattern of staining with NBT was
      similar to that with endothelial NOS and suggests that other isoforms of NOS are
      not present in the placental unit.

PMID- 7507243
TI  - Antigenic heterogeneity of human cytotrophoblast and evidence for the transient
      expression of MHC class I antigens distinct from HLA-G.
AB  - Expression of MHC class I antigens on trophoblast populations in first trimester
      human chorionic villous tissue was assessed by immunohistology. Antibodies used
      were W6/32 which recognizes a non-polymorphic framework determinant of HLA- A, 
      B, -C, MHM5 specific for HLA-B, C and 4E and B23.1 which are specific for HLA-B.
      Syncytiotrophoblast and villous cytotrophoblast were negative with all the anti
      (HLA class I) antibodies tested. Interstitial trophoblast cells within the
      maternal decidua were identified with a new antibody, NDOG5, which is specific
      for extravillous cytotrophoblast. Double labelling showed that they bind W6/32
      but not 4E, MHM5 or B23.1; consistent with the expression of the monomorphic HLA
      G. In contrast the cytotrophoblast cells of the cell islands and cytotrophoblast
      shell, which also express the NDOG5 antigen, were positive with W6/32, 4E, MHM5
      and B23.1. Cell column cytotrophoblast cells were negative with all four MHC
      class I antibodies. These results suggest that differentiation of cytotrophoblast
      from noninvasive to invasive forms is associated with transient expression of
      class I antigens other than HLA-G on cytotrophoblast shell and cell island
      cytotrophoblast.

PMID- 7507244
TI  - [The use of DNA probes for the diagnosis of pulmonary tuberculosis].
AB  - Mycobacterium-specific nonradioactive DNA probes have been tested able to detect
      mycobacteria in clinical samples (sputum, bronchoalveolar lavage) for 48 hours.
      The probes sensitivity makes up 1000-10,000 cells. Molecular hybridization
      confirms the results of DNA-probe diagnostic conclusion of tuberculosis more
      frequently than the results of standard microbiological tests.

PMID- 7507245
TI  - STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human
      bone marrow cells and is involved in the proliferation of early progenitor/stem
      cells.
AB  - We cloned the cDNA for stem cell tyrosine kinase 1 (STK-1), the human homolog of
      murine Flk-2/Flt-3, from a CD34+ hematopoietic stem cell-enriched library and
      investigated its expression in subsets of normal human bone marrow. The cDNA
      encodes a protein of 993 aa with 85% identity and 92% similarity to Flk-2/Flt-3.
      STK-1 is a member of the type III receptor tyrosine kinase family that includes
      KIT (steel factor receptor), FMS (colony-stimulating factor 1R), and platelet
      derived growth factor receptor. STK-1 expression in human blood and marrow is
      restricted to CD34+ cells, a population greatly enriched for stem/progenitor
      cells. Anti-STK-1 antiserum recognizes polypeptides of 160 and 130 kDa in several
      STK-1-expressing cell lines and in 3T3 cells transfected with a STK-1 expression
      vector. Antisense oligonucleotides directed against STK-1 sequences inhibited
      hematopoietic colony formation, most strongly in long-term bone marrow cultures.
      These data suggest that STK-1 may function as a growth factor receptor on
      hematopoietic stem and/or progenitor cells.

PMID- 7507246
TI  - Negative regulation of early B lymphopoiesis by interleukin 3 and interleukin 1
      alpha.
AB  - We recently developed a two-step methyl cellulose culture system for murine
      lymphohemopoietic progenitors that are capable of differentiation along the
      myeloid and B-lymphoid lineages. In this system, two-factor combinations, which
      include steel factor plus interleukin (IL) 6, IL-11, or granulocyte colony
      stimulating factor effectively supported the lymphomyeloid potential of primary
      colonies. Interestingly, IL-3 could neither replace nor act synergistically with
      steel factor in maintaining the B-lymphoid potential of the primary colonies
      although the frequency of colony formation was the same with IL-3 and steel
      factor. We now report that addition of IL-3 or IL-1 alpha to a permissive system
      suppresses the B-lymphoid potential of primitive progenitor cells in primary
      culture in dose-dependent fashion. In vivo transfer of the primary colonies to
      scid mice confirmed the suppressive effects of IL-3 and IL-1 alpha. In addition,
      IL-1 alpha inhibited pre-B-cell colony formation in the secondary culture. Once
      pre-B-cell colonies had formed in secondary culture, neither factor affected the
      proliferation of the pre-B cells. These results suggest negative regulatory roles
      for IL-3 and IL-1 alpha in early stages of B lymphopoiesis.

PMID- 7507247
TI  - Relationship of a non-cystic fibrosis transmembrane conductance regulator
      mediated chloride conductance to organ-level disease in Cftr(-/-) mice.
AB  - Although loss of cystic fibrosis transmembrane conductance regulator (CFTR)
      mediated Cl- channel function is common to all epithelia in cystic fibrosis (CF)
      patients, the severity of disease varies in different organs. We hypothesized
      that differences in disease severity in CF relate to the expression of an
      "alternative" plasma membrane Cl- conductance. In CF mice [Cftr(-/-); mice
      homozygous for Ser-489 to Xaa mutation], which do not express cAMP CFTR-mediated
      Cl- secretion, we surveyed organs that exhibit a range of disease severity for a
      Ca(2+)-mediated apical membrane epithelial Cl- conductance. This alternative
      conductance (Cl-a) was detected in epithelia of organs from CF mice that exhibit
      a mild disease phenotype (airway, pancreas) but not in epithelia with a severe
      phenotype (small, large intestine). We conclude that (i) there is an
      intracellular Ca(2+)-regulated Cl- conductance that is molecularly distinct from
      CFTR; and (ii) the level of expression of this alternative Cl- conductance in the
      epithelium is an important determinant of the severity of organ-level disease in
      CF.

PMID- 7507248
TI  - Cloning and in situ localization of a brain-derived porin that constitutes a
      large-conductance anion channel in astrocytic plasma membranes.
AB  - We have cloned a protein from bovine brain, brain-derived voltage-dependent anion
      channel 1 (BR1-VDAC), that is identical to a recently sequenced plasmalemmal
      bound porin from human lymphocytes. mRNA hybridization indicates that BR1-VDAC is
      widely distributed throughout nervous and nonnervous tissues. In situ
      localization substantiated that the BR1-VDAC is associated with the plasmalemma
      of astrocytes. A monoclonal antibody that recognizes the N terminus of the BR1
      VDAC protein completely blocks an astrocytic high-conductance anion channel that
      has electrophysiological similarities with the mitochondrial VDAC. Since the high
      conductance anion channel in astrocytes has been shown to respond to hypoosmotic
      solutions, its molecular identification provides the basis for a better
      understanding of volume regulation in brain tissue.

PMID- 7507249
TI  - Marked infidelity of human immunodeficiency virus type 1 reverse transcriptase at
      RNA and DNA template ends.
AB  - Human immunodeficiency virus type 1 (HIV-1) is genetically highly variable. This
      is attributed to the error-prone nature of HIV-1 replication and its proclivity
      for recombination. During replication and recombination, reverse transcriptase
      (RT) must polymerize DNA to the 5' ends of multiple RNA and DNA template termini
      while converting HIV-1 RNA to double-stranded DNA. We have determined the
      fidelity of HIV-1 RT in vitro during polymerization to the 5' ends of HIV-1 long
      terminal repeat DNA template sequences and to the end of a partial HIV-1 genomic
      RNA template that mimics a recombination intermediate. HIV-1 RT readily extended
      recessed DNA primers to form full-length blunt-end DNA-DNA and DNA-RNA duplexes.
      In addition, HIV-1 RT catalyzed high yields of products with one to four extra
      nucleotides at the 3' ends of the nascent DNAs. These products were formed
      processively via a nontemplated mechanism that is highly specific for the
      addition of purine nucleotides (A > G >> T > or = C). Thus, HIV-1 RT is extremely
      unfaithful at both DNA and RNA template ends, introducing errors (extra
      nucleotides) in one out of every two or three nascent strands processively
      polymerized. This error rate is 1000 times higher than for HIV-1 RT-catalyzed
      errors at internal template positions. Blunt-end additions were also catalyzed by
      other retroviral RTs at relative rates of HIV-1 approximately Moloney murine
      leukemia virus > avian myeloblastosis virus. These data suggest a potentially
      important mechanism for retroviral mutation mediated by nontemplated blunt-end
      addition of purines prior to forced copy-choice recombination.

PMID- 7507250
TI  - Role of antibody and T cells in the long-term inhibition of IgE synthesis.
AB  - We have shown that the long-term inhibition of IgE synthesis associated with
      perinatal inoculation of syngeneic IgE is accompanied by the synthesis of
      autoantibodies to IgE. Synthesis of IgE can also be inhibited by passive transfer
      of syngeneic anti-IgE antibodies. In the present investigation we made use of
      adoptive transfer experiments to assess the relative roles of antibodies and T
      cells in the inhibitory process. It was found that spleen cells from IgE
      suppressed mice (synthesizing anti-IgE antibodies) could adoptively transfer the
      state of inhibition to syngeneic adult mice. The inhibition occurred only under
      conditions in which the recipient mice synthesized anti-IgE antibodies. Separated
      B cells, CD4+ T cells, CD8+ T cells, or a mixture of B and CD8+ T cells were
      ineffective. However, strong inhibition of IgE synthesis (as indicated by serum
      levels and numbers of IgE-secreting cells in the spleen) was observed after
      transfer of a mixture of B cells and CD4+ (helper) T cells. The results indicate
      that in this experimental model anti-IgE antibodies are the suppressive agent and
      that T cells do not play a role other than that of providing help to B cells for
      anti-IgE synthesis.

PMID- 7507251
TI  - Plant mitochondrial nucleic acid sequences as a tool for phylogenetic analysis.
AB  - To evaluate the potential of mitochondrial nucleic acid sequences as a
      phylogenetic tool, we have analyzed cytochrome oxidase subunit III (coxIII)
      coding sequences in representatives of the major groups of land plants. The
      phylogenetic tree derived from these mitochondrial sequences confirms the
      monophyletic origin of land plant mitochondria with the general order and descent
      of land plants deduced by other molecular, physiological, and morphological
      traits. The mitochondrial sequences strongly suggest a close phylogenetic
      relationship between Bryophyta and Lycopodiatae, whereas Psilophytatae cluster
      with the other vascular plants. In addition to the high sequence similarity, both
      Hepaticophytina and Lycopodiatae contain a related intron in the coxIII gene
      that, to our knowledge, is not found in any other plant species. The slowly
      evolving mitochondrial sequences of plants are shown to provide a useful
      phylogenetic tool to evaluate distant evolutionary relationships within this
      kingdom.

PMID- 7507252
TI  - Stress-inducible gene of Salmonella typhimurium identified by arbitrarily primed
      PCR of RNA.
AB  - Fingerprinting of RNA by arbitrarily primed PCR (RAP) can be used to identify
      conditionally expressed genes in prokaryotes. Differential gene expression in
      Salmonella typhimurium LT2 in response to peroxide treatment was examined as a
      system in which to demonstrate this strategy. This treatment models the induction
      of bacterial protective proteins that may occur when mammalian phagocytes use
      peroxide to fight S. typhimurium infection. To identify genes inducible by
      hydrogen peroxide stress, total RNA from peroxide-treated and untreated bacterial
      cultures were RAP fingerprinted with six different arbitrarily selected primers.
      A 435-base RAP product that was differentially amplified by RAP using the reverse
      sequencing primer was cloned and sequenced. Northern blot analysis confirmed that
      the RNA corresponding to this clone, RSP435, was induced when bacteria were
      treated with hydrogen peroxide. The RNA was not induced in an oxyR1 mutant that
      constitutively expressed a subset of hydrogen peroxide-inducible genes. Using
      pulsed-field gel electrophoresis and dot blot hybridization to an array of
      induced Mud-P22 integrations, the gene corresponding to RSP435 was mapped to two
      places, one between 19 and 21.5 min and one between 56 and 57 min. Thus, two
      similar or identical stress-inducible genes were found in different parts of the
      genome. Identification, cloning, and mapping of the conditionally expressed
      RSP435 cDNA were performed entirely by physical means, demonstrating that the
      strategy should complement genetic methods for many prokaryotic or
      archaebacterial systems and should be applicable to organisms in which genetic
      methods are difficult to perform or have not yet been developed.

PMID- 7507253
TI  - Minimum structural requirements for peptide presentation by major
      histocompatibility complex class II molecules: implications in induction of
      autoimmunity.
AB  - The precise mechanisms of failure of immunological tolerance to self proteins are
      not known. Major histocompatibility complex (MHC) susceptibility alleles, the
      target peptides, and T cells with anti-self reactivity must be present to cause
      autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a murine
      model of a human autoimmune disease, multiple sclerosis. In EAE, residues 1-11 of
      myelin basic protein (MBP) are the dominant disease-inducing determinants in PL/J
      and (PL/J x SJL/J)F1 mice. Here we report that a six-residue peptide (five of
      them native) of MBP can induce EAE. Using peptide analogues of the MBP-(1-11)
      peptide, we demonstrate that only four native MBP residues are required to
      stimulate MBP-specific T cells. Therefore, this study demonstrates lower minimum
      structural requirements for effective antigen presentation by MHC class II
      molecules. Many viral and bacterial proteins share short runs of amino acid
      similarity with host self proteins, a phenomenon known as molecular mimicry.
      Since a six-residue peptide can sensitize MBP-specific T cells to cause EAE,
      these results define a minimum sequence identity for molecular mimicry in
      autoimmunity.

PMID- 7507254
TI  - The effect of high pressure on glycine- and kainate-sensitive receptor channels
      expressed in Xenopus oocytes.
AB  - The effect of high pressure on the response to glycine or kainate of voltage
      clamped Xenopus oocytes micro-injected with messenger-RNA derived from either rat
      spinal cord or whole brain, respectively, has been investigated. Current
      responses were measured at 1 bar (= 10(5) Pa), 50 bar, 100 bar and 150 bar, with
      PO2 fixed at 1 bar and the balance helium. Glycine elicited a depolarizing
      current response which was antagonized by nanomolar concentrations of strychnine.
      The responses reversibly desensitized, with a decay constant of 0.01 s-1, when
      glycine concentrations greater than 250 microM were used. The decay constant was
      insensitive to both glycine concentration and pressure. Resensitization was
      complete within 4 min. Kainate elicited a depolarizing current which was non
      desensitizing. The response was slightly sensitive to glutamate diethyl ester (50
      microM), which increased the EC50 by 25%. The action of glycine was highly
      pressure sensitive. The dose-response curves established at 50 bar, 100 bar and
      150 bar were shifted progressively to the right, with no effect on the maximal
      current. The EC50 increased from 216 microM to 296 microM at 50 bar, to 345
      microM at 100 bar, and to 425 microM at 150 bar. The action of kainate was
      unaffected by pressure. No shift in the dose-response curves was established, nor
      was there any effect on the maximum current. The EC50 was 113 microM at 1 bar,
      and 111 microM at both 50 bar and 100 bar.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507257
TI  - Improving decision making at school entry medicals--completing the audit cycle.
AB  - An audit of decision making at the entry medical was carried out to ascertain how
      doctors responded to childrens' physical, developmental and psychosocial
      adversity. Using specifically designed recording protocols, eleven doctors
      recorded their activity at 922 entry medicals over one term. The results were
      discussed, protocols of decision making were prepared and ten doctors re-ran the
      exercise assessing a further 783 over one term; one year later. The proportions
      discussed with headteachers, referred to agencies and selected for review varied
      in both data sets, and certain trends emerged. More experienced doctors were more
      likely to discuss vulnerabilities and did so for 18 to 25% of entrants in
      addition to the 20-30% referred or selected for review. The introduction of
      guidelines increased the overall proportion of children discussed with teachers
      and reduced, in part, the proportion scheduled for review. This study informs the
      debate about selective entry medicals. The findings will be of interest to
      commissioners of health care who have the responsibility for contracting for
      school entry assessments.

PMID- 7507255
TI  - Conversion of perianth into reproductive organs by ectopic expression of the
      tobacco floral homeotic gene NAG1.
AB  - Mutations in the AGAMOUS (AG) gene of Arabidopsis thaliana result in the
      conversion of reproductive organs, stamens and carpels, into perianth organs,
      sepals and petals. We have isolated and characterized the putative AG gene from
      Nicotiana tabacum, NAG1, whose deduced protein product shares 73% identical amino
      acid residues with the Arabidopsis AG gene product. RNA tissue in situ
      hybridizations show that NAG1 RNA accumulates early in tobacco flower development
      in the region of the floral meristem that will later give rise to stamens and
      carpels. Ectopic expression of NAG1 in transgenic tobacco plants results in a
      conversion of sepals and petals into carpels and stamens, respectively,
      indicating that NAG1 is sufficient to convert perianth into reproductive floral
      organs.

PMID- 7507256
TI  - Fenfluramine challenge test as a predictor of outcome in major depression.
AB  - It has been reported that low pretreatment cerebrospinal fluid (CSF) 5
      hydroxyindoleacetic acid (5-HIAA) levels may correlate with better clinical
      response to selective serotonin reuptake inhibitors (SSRI) compared to non
      serotonergic antidepressant drugs. We examined the hypothesis that serotonergic
      system status, as measured by the prolactin (PRL) response to fenfluramine (FEN),
      may predict outcome in a heterogenous sample treated with various types of
      antidepressant treatment. Higher PRL response predicted a favorable outcome for
      males and females treated with either pharmacotherapy, psychotherapy [milieu
      therapy with or without cognitive behavior therapy (CBT)], or electroconvulsive
      therapy (ECT). All patients in the high PRL response group responded to
      antidepressant therapies. Patients receiving ECT had the highest proportion of
      treatment responders, the highest degree of treatment response, and, unlike drug
      or psychotherapy treatment, improved significantly whether in the high or low PRL
      response group. PRL response to a single dose fenfluramine challenge may be a
      useful predictor of response to pharmacological or psychotherapeutic treatments
      in major depression. By contrast, ECT is an effective short-term treatment
      independent of pretreatment serotonergic responsivity.

PMID- 7507258
TI  - Three methods of oral health education in secondary schools.
AB  - In 1990, three methods of oral health education (OHE) were implemented in three
      secondary schools in the city of Pori, Finland, one method in each school. The
      traditional OHE consisted of a lecture given by a dentist with the aid of
      transparencies and slides. The peer OHE consisted of a lecture given by six
      pupils from the upper grades. These pupils used transparencies and extracts of
      video films and had a classroom exhibition with pictures, slogans, and dental
      aids and instruments. The self-teaching OHE was based on an exhibition from which
      the pupils searched for the information themselves. After the programs, the
      pupils' opinions about the method itself, its contents and implementation,
      knowledge about certain oral health issues, and the possible effect of the method
      were determined by a questionnaire. The attitudes and opinions were most positive
      in the peer OHE group. The traditional OHE was quite well accepted, but the self
      teaching method was not very successful. The participants in the traditional OHE
      more often felt that they had been encouraged to pursue good oral health habits.
      In all groups, the topic considered to be the most boring was tooth brushing.
      Peer OHE can be recommended for Finnish secondary schools. The issue of tooth
      brushing should be played down, however, as too frequent repetition of the topic
      may cause more negative attitudes towards oral health education and practices.

PMID- 7507260
TI  - Down-regulation of L-selectin surface expression by various leukocyte isolation
      procedures.
AB  - L-selectin, a cell surface glycoprotein expressed on lymphocytes, granulocytes,
      and monocytes, has been implicated in lymphocyte homing and extravasation of
      phagocytic leukocytes into areas of inflammation. Considerable differences of L
      selectin expression among various individuals has been reported, with clinical
      correlations to perinatal events, maturation, and circadian rhythm. In this
      study, L-selectin expression of various white blood cells was found to be
      differentially sensitive to ficoll-hypaque or percoll density gradient
      centrifugation. After density gradient centrifugation, a significant loss of
      median monocyte L-selectin expression was observed when compared to time and
      temperature-matched controls or results obtained by whole blood incubation with
      anti-L-selectin monoclonal antibodies followed by simultaneous leukocyte fixation
      and red cell lysis. Mock treatment itself was associated with a variable L
      selectin loss of monocytes but not lymphocytes or granulocytes. Ficoll-hypaque or
      percoll density gradient centrifugation resulted in significant L-selectin down
      regulation of lymphocytes while granulocytes separated from lymphocytes and
      monocytes by ficoll-hypaque or percoll retained full L-selectin surface
      reactivity. L-selectin downregulation was seen also after colloid sedimentation
      with hydroxy-ethyl starch. It is concluded that unseparated blood should be used
      for measuring L-selectin expression.

PMID- 7507259
TI  - Tumour promoters/protein-kinase C activators augment the survival and function of
      human monocyte-derived macrophages in long-term cultures.
AB  - In this study the effect of various Protein kinase C (PKC) activators/tumour
      promoters on the maturation and activity of human peripheral blood monocytes was
      examined. Monocytes were cultured in the absence or presence of various PKC
      activators for up to 2 weeks, and examined for the number of adherent cells,
      expression of myeloperoxidase enzymes, CD14 antigens, mannose/N-acetylglucosamine
      (Man/GlcNAc) receptors, and the production of TNF-alpha. The presence of PKC
      activators in cultures of monocyte-derived macrophages (HuMoDM) prevented the
      loss in the number of initially plated monocytes, otherwise observed in long-term
      tissue cultures with time of incubation. This effect of PKC activators on
      monocyte survival was diminished in the presence of PKC inhibitors. HuMoDM
      obtained in the presence of PKC activators maintained a normal differentiation
      pattern, as was evident by the loss of granular myeloperoxidase enzymes and CD14
      antigens, and the acquisition of membrane Man/GlcNAc receptors. HuMoDM which
      differentiated in the presence of PKC activators also released TNF-alpha in
      comparable amounts to freshly harvested human monocytes. PKC activators/tumour
      promoters augmented the viability of long-term cultures of human monocyte-derived
      macrophages. Such macrophages may facilitate cell and molecular biology studies
      of differentiated human macrophages.

PMID- 7507261
TI  - Outpatient transurethral incision of the prostate under local anesthesia:
      operative results, patient security and cost effectiveness.
AB  - Thirty patients with small and medium-sized obstructive prostates were operated
      by transurethral incision of the prostate (TUIP) under local anesthesia as an
      outpatient procedure. All patients except one tolerated this manoeuvre without
      any complications or discomfort. The obstructive symptoms were relieved in all
      patients; however, 6 patients had lasting irritative symptoms, 2 of whom were
      cured after TURP. The costs of TUIP was calculated to be one sixth of that of
      TURP. During one year follow-up 5 patients were found to have prostate cancer
      despite careful rectal examination and PSA measurement preoperatively. In
      conclusion, TUIP may be carried out as safely and cost-effectively as an
      outpatient procedure and is beneficial in patients with predominantly obstructive
      symptoms. However, careful investigations concerning possible prostate cancer
      must be undertaken in this group of patients with small but symptomatic
      prostates.

PMID- 7507262
TI  - Effective tumor vaccine generated by fusion of hepatoma cells with activated B
      cells.
AB  - Fusion of BERH-2 rat hepatocellular carcinoma cells with activated B cells
      produced hybrid cells that lost their tumorigenicity and became immunogenic.
      Syngeneic rats injected with BERH-2-B hybrid cells became resistant to challenge
      with parental BERH-2 cells, and rats with established BERH-2 hepatomas were cured
      by subsequent injection of BERH-2-B cells. Both CD4+ and CD8+ cells were
      essential for the induction of protective immunity; however, only CD8+ cells were
      required for the eradication of BERH-2 tumors. The generation of hybrid tumor
      cells that elicit antitumor immune responses may be a useful strategy for cancer
      immunotherapy.

PMID- 7507263
TI  - Intensive therapy for adult acute lymphoblastic leukemia: preliminary results of
      the idarubicin/vincristine/L-asparaginase/prednisolone regimen.
AB  - Between June 1991 and September 1992, 80 patients with adult acute lymphoblastic
      leukemia (ALL) (newly diagnosed, n = 68; relapsed or refractory ALL, n = 7;
      lymphoid blast transformation of Philadelphia chromosome-positive chronic
      myelogenous leukemia [LT-CML], n = 5) were managed with a combination regimen
      consisting of idarubicin 36, 20, or 10 mg/m2 plus vincristine, L-asparaginase,
      and prednisolone (IVAP-1, -2, -3). Three patients with LT-CML and four with
      relapsing ALL had a complete remission. In the group of newly diagnosed patients
      aged 15 to 60 years treated with IVAP-1, the complete remission rate was only 44%
      due to the high incidence of toxic deaths. In contrast, 39 of 44 cases who
      subsequently received IVAP-2 achieved a complete remission (89%, P = .001), as
      did 62% of elderly patients who received IVAP-3. Hematologic and nonhematologic
      toxicity was significantly reduced with IVAP-2 compared with IVAP-1. The use of
      recombinant human granulocyte colony-stimulating factor in 24 patients was not
      associated with a reduced duration of granulocytopenia less than 0.5 x 10(9)/L,
      although there was a lower incidence of documented infections in patients
      receiving granulocyte colony-stimulating factor than in controls. Post-remission
      intensification with idarubicin-based courses, high-dose therapy with autologous
      bone marrow stem cell rescue, and rotational weekly therapy was feasible and its
      toxicity was manageable. These preliminary findings indicate that IVAP-2
      (idarubicin 20 mg/m2) is a highly effective and well-tolerated regimen for
      remission induction of adult ALL.

PMID- 7507264
TI  - High-dose cytarabine, idarubicin, and granulocyte colony-stimulating factor
      remission induction therapy for previously untreated de novo and secondary adult
      acute myeloid leukemia.
AB  - This report describes the preliminary results of the remission induction phase of
      a protocol for previously untreated de novo and secondary acute myeloid leukemia
      (AML) designed to deliver very intensive therapy over a brief period of time
      using hematopoietic growth factor support. Remission induction therapy consisted
      of cytarabine 3 g/m2 (1.5 g/m2 for age > 50 years) intravenously over 1 hour
      every 12 hours for 12 doses and idarubicin 12 mg/m2 over 30 minutes on days 2, 3,
      and 4 of cytarabine, followed by 10 micrograms/kg granulocyte colony-stimulating
      factor subcutaneously daily until the absolute neutrophil count increased to > or
      = 5.0 x 10(9)/L on 2 consecutive days. Twenty-seven patients received all the
      planned doses of chemotherapy. The complete remission (CR) rate to a single
      course of therapy was 65% in 20 patients with de novo AML (median age, 60.5
      years; age range, 26 to 78 years); for those aged less than 60 and > or = 60
      years, the CR rates were 90% and 40%, respectively. In contrast, only two of 10
      patients with secondary AML (median age, 68 years; age range, 35 to 77 years)
      achieved a CR. The median time from initiation of chemotherapy to recovery of 0.5
      x 10(9)/L neutrophils in de novo AML patients achieving CR was 20 days (range, 18
      to 23 days). Median times to last platelet transfusion and to 100 x 10(9)/L
      platelet count were 23 days (range, 18 to 41 days) and 28 days (range, 24 to 97
      days), respectively. The major nonhematologic toxicity was transient
      hyperbilirubinemia, which was observed in 64% of patients. Reversible cerebellar
      toxicity was seen in three patients. Thus, idarubicin at full dose (12 mg/m2 x 3
      days) may be safely administered with high-dose cytarabine, even in elderly
      patients. The use of granulocyte colony-stimulating factor is associated with
      rapid neutrophil recovery without obvious toxicity. The CR rate for de novo AML
      patients treated with a single course of high-dose cytarabine, idarubicin, and
      granulocyte colony-stimulating factor is at least comparable to CR rates achieved
      with standard-dose cytarabine and anthracycline regimens. The response of
      secondary AML patients remains inferior.

PMID- 7507265
TI  - Osmotic stress variants in Chinese hamster cells.
AB  - Stable variants resistant to hypertonic stress have been obtained from V79 cells
      by one-step selection in media supplemented with graded concentrations of NaCl.
      Such variants retain a potential for resistance when isolated and propagated in
      isotonic media. On replating in graded NaCl, a family of dose-response curves is
      obtained, rising in level of resistance according to the degree of hypertonicity
      used to isolate the variants initially. In hybrids between variants and sensitive
      cells, phenotypic expression of resistance to hypertonic NaCl is recessive.
      Stable variants can also be isolated by one-step selection in media made
      hypertonic with D-mannitol. Clonal sublines selected with mannitol, as well as
      those obtained with NaCl, are resistant to both types of hypertonic media.
      Fluctuation tests in media supplemented with NaCl show that resistance arises
      spontaneously and at random, with measured rates of variation that depend on the
      concentration of NaCl used for selection. Treatment of sensitive cells with 5
      azacytidine increases the frequency of resistant variants in assays with high
      levels of added NaCl but is less effective when selection is performed at lower
      concentrations. Exposure to ethyl methane sulfonate has little or no effect on
      variant frequency.

PMID- 7507267
TI  - Expression of cytochrome P450s and microsomal epoxide hydrolase in primary
      cultures of human umbilical vein endothelial cells.
AB  - In view of the potential role of the cytochrome P450 (CYP) and microsomal epoxide
      hydrolase (mEH) biotransformation enzymes in the metabolism of protoxicants in
      the circulatory system, we examined CYP and mEH expression in several primary
      cultures of human umbilical vein endothelial cells (HUVEC), each established from
      a different individual. Total RNA was isolated from untreated cells and cells 72
      hr after exposure to dimethyl sulfoxide (DMSO), Arochlor 1254 (PCB), and beta
      naphthoflavone (beta NF). Specific mRNA transcripts were examined by Northern
      blotting and reverse transcriptase-coupled polymerase chain reaction (RT/PCR)
      analyses. CYP2E1, CYP3A, and CYP1A2 mRNAs were not detectable in any of the
      cultures by Northern blot analysis with radiolabeled oligomer probes; however,
      CYP1A1 mRNA was detected using this procedure in HUVEC cultures exposed to beta
      NF for 72 hr. Using RT/PCR, constitutive levels of CYP1A1, CYP1A2, CYP2E1, and
      CYP3A gene expression in HUVEC cultures were evident; however, constitutive
      CYP2B6 mRNA was not detected. Constitutive CYP1A2 transcript levels were detected
      in four of six HUVEC cultures, but levels varied between individual cultures.
      CYP1A2 mRNA levels were also increased in HUVEC cultures exposed to PCB and beta
      NF. No increases in the levels of CYP2E1 and CYP3A mRNAs were observed in HUVEC
      cells subsequent to PCB or beta NF exposures. Constitutive CYP2E1 transcript
      levels were present in all HUVEC cultures examined and varied among individuals.
      All HUVEC cultures examined for mEH activity exhibited constitutive levels of mEH
      which varied 40% between individual cultures and produced on average, 1.51 pmol
      benzo[a]pyrene 4,5-dihydrodiol per milligram protein per minute of reaction.
      Thus, these results demonstrate that human endothelial cells express CYP and mEH
      gene products and suggest that these enzymes may play important roles in
      determining metabolic fates for circulating protoxicants.

PMID- 7507266
TI  - The use of methylthioadenosine phosphorylase activity to select for human
      chromosome 9 in interspecies and intraspecies hybrid cells.
AB  - Methylthioadenosine phosphorylase (MTAP) is an enzyme that functions in a salvage
      pathway for adenine synthesis. The locus that encodes MTAP activity has been
      mapped to human chromosome 9 (9q12-9pter) by analysis of mouse x human somatic
      cell hybrids. Cells that have MTAP activity will stop proliferating, and
      eventually die in the presence of azaserine, an inhibitor of de novo purine
      synthesis, but can be rescued by the addition of methylthioadenosine (MTA) to the
      culture medium. Some mouse and human tumor cells lack MTAP activity and can not
      grow in the presence of azaserine and MTA. We fused MTAP competent human
      fibroblast cells to MTAP deficient mouse L-cells and selected for somatic cell
      hybrids, containing MTAP activity, in medium containing azaserine and MTA. In a
      separate experiment, a CHO cell x human fibroblast somatic cell hybrid,
      containing a normal copy of human chromosome 9, was used to prepare microcells,
      which were fused to an MTAP-deficient human leukemic cell line, CCRF-CEM. Somatic
      cell and microcell hybrids were shown to retain human chromosome 9 by
      fluorescence in situ hybridization using probes that hybridize to the interferon
      alpha and -beta 1 genes on human chromosome 9 (9p21), and the centromere of human
      chromosome 9. This is the first report of complementation for MTAP activity being
      used to select for somatic cell hybrids and microcell hybrids that retain a human
      chromosome 9.

PMID- 7507268
TI  - Cadmium toxicity in rat pheochromocytoma cells: studies on the mechanism of
      uptake.
AB  - The uptake and toxicity of cadmium were compared in two rat pheochromocytoma cell
      lines: PC12 cells, which express voltage-sensitive calcium channels, and PC18
      cells, which do not. PC12 but not PC18 cells responded to depolarization with an
      increase in 45Ca2+ uptake and an increase in the concentration of cytoplasmic
      free calcium ion, [Ca2+]i. These responses were blocked by the dihydropyridine
      calcium channel antagonist nimodipine and amplified by the agonist BAY K8644,
      drugs selective for L-type channels. Cadmium caused death of PC12 cells with an
      LC50 of 12 microM. Inclusion of high K+ with the agonist BAY K8644 shifted the
      kill curve to the left (LC50 = 6 microM). whereas nimodipine protected against
      cadmium toxicity (LC50 = 30 microM). In contrast, drugs acting on L-type calcium
      channels did not affect Cd2+ toxicity for PC18 cells (LC50 15 microM). Fura 2 was
      used to measure intracellular free Cd2+ by fluorescence ratio methods. Addition
      of 25 microM Cd2+ to both PC12 and PC18 cells caused a rise in the 340/380
      fluorescence ratio attributable to the uptake of Cd2+, since it was almost
      completely reversed by chelating extracellular Cd2+ and adding a membrane
      permeant chelator of heavy metals. Cd2+ addition resulted in a gradual increase
      in Fura 2 fluorescence in both PC12 and PC18 cells, but depolarization with BAY
      K8644 increased the apparent rate of Cd2+ uptake only for the PC12 cells. Cd2+
      fluorescence appeared to be concentrated near the plasma membrane. The results
      confirm the potential involvement of calcium channels in cadmium transport and
      extend the use of intracellularly trapped fluorescent dyes to monitor
      intracellular free cadmium ion concentration.

PMID- 7507269
TI  - What makes an mRNA anti-sense-itive?
AB  - Antisense RNA has been used for some time as a versatile tool for silencing gene
      expression. There is ample evidence for gene regulation by endogenous antisense
      transcripts in prokaryotes and increasing insight into the molecular mechanisms
      underlying such regulation. The introduction of antisense gene constructs into
      eukaryotes has now become routine but the mechanisms by which gene expression is
      inhibited are barely understood. In recent years, several examples of endogenous
      eukaryotic antisense transcripts have been discovered, some of which probably
      serve regulatory functions. Here we will discuss a model to explain mechanisms of
      antisense-mediated gene silencing.

PMID- 7507270
TI  - Analysis of peripheral blood lymphocyte populations and immune function from
      children exposed to cyclosporine or to azathioprine in utero.
AB  - We have analyzed PBL from 7 children exposed to CsA in utero and 4 children
      exposed to AZA in utero. Expression of CD3, CD4, CD8, and CD20 were normal for
      both groups of children; however, significant differences were detected in the
      expression of CD45RA, CD45R0, and CD29. While CsA-exposed children had higher
      density of CD45RA, and a higher proportion of CD45RA+R0- T cells, than did
      unexposed children, those exposed to AZA alone had decreased CD45RA+ and a large
      increase in CD45RA-R0+ T cells. It appears the exposure to CsA slightly delays T
      cell development, whereas exposure to AZA, without concomitant exposure to CsA,
      accelerates development to that of an adult. The effects of CsA abrogated the
      effects of AZA when both were present during pregnancy. The expression of CD29,
      the beta 1-integrin, on T cells has been linked to enhanced ability to respond to
      recall antigens and to home to sites of infection. Among children exposed to CsA,
      T cells from cord blood and a 5-month-old infant have a normal CD29 profile.
      However from 1 to 6 years of age the proportion of T cells expressing a high
      density of CD29 is significantly lower (4-fold) than that of T cells from
      unexposed children. Because these children have no outward signs of
      immunodeficiency, we postulate that this low proportion is still sufficient for
      normal immune responsiveness. The distribution of CD29 on T cells was different
      for the 3 study groups. Among CsA-exposed children, although the proportion of
      CD29hi T cells was much reduced, all were CD45RA+, as was also the case for
      unexposed children. In contrast, among children exposed only to AZA, the majority
      of CD29hi T cells were CD45R0+. Serological testing indicated that immunoglobulin
      and complement levels, as well as seroconversion in response to vaccination, were
      normal among CsA-exposed children, with no detectable autoantibodies to cellular
      or tissue components, including parietal cells. Unlike T cell development in
      inbred rodents, the immune system in humans appears to be remarkably resilient,
      and successfully adapts to the presence of CsA during its early developmental
      stages. This work suggests that the presence of CsA throughout pregnancy has only
      a minimal effect on fetal immune development and appears to have less impact on T
      cells than does exposure to AZA only. We conclude that children exposed to CsA in
      utero are not likely to be at risk of immunodeficiency or autoimmunity.

PMID- 7507271
TI  - IL-6 independent monocyte/B cell defect in renal transplant recipients with long
      term stable graft function.
AB  - We showed previously that the B cell response in renal transplant recipients with
      long-term stable graft function (ST patients) is significantly affected by T
      suppressor activity. To further assess the role of the monocyte/B cell
      compartment in B cell regulation, we tested B cell responses in 30 ST patients (>
      1 year after transplant) and 15 patients with chronic rejection (CR patients).
      PWM was used for T cell-dependent B cell stimulation in an allogeneic coculture
      system, and SAC I for T cell- and monocyte-independent B cell stimulation. B cell
      responses were assessed in a reverse hemolytic plaque assay and by ELISA
      determination of IgM, IgG, and IL-6 in culture supernatants. In PWM-stimulated
      cultures of ST patients, we found a diminished immunoglobulin-secreting cell
      (ISC) formation (P < 0.0001 and P < 0.05, compared with controls and CR patients,
      respectively) and diminished IgM secretion (P = 0.06 and P < 0.01, respectively),
      whereas CR patients and controls were not significantly different. Two of 35 (6%)
      controls and 3 of 15 (20%) CR patients, in contrast to 20 of 30 (67%) ST
      patients, displayed defective ISC formation (P < 0.0001). This defective B cell
      response may be the result of reduced CD36+ monocyte counts in ST patients (P <
      0.005), as PWM-stimulated B cell responses and CD36+ cell counts were
      significantly associated (P < 0.05, ISC and IgM response). A role of monocytes in
      the impairment of B cell function is further supported by decreased plasma
      neopterin levels in ST compared with CR patients (P = 0.0001), a significant
      association between plasma neopterin and PWM-stimulated B cell responses (P <
      0.05, ISC response; P = 0.0001, IgM response), and by the finding that B cell
      responses in ST patients after monocyte-independent stimulation with SAC I were
      unaffected. ST and CR patients showed no significant differences in B cell
      subsets, plasma IL-6, or IL-6 responses of mitogen-stimulated cultures. Our data
      indicate that an IL-6-independent monocyte or B cell defect plays a role in the
      maintenance of stable transplant function.

PMID- 7507272
TI  - Conversion from cyclosporine to FK506 for salvage of immunocompromised pediatric
      liver allografts. Efficacy, toxicity, and dose regimen in 23 children.
AB  - Twenty-three pediatric liver transplant recipients (median age 3.9 years) were
      converted from cyclosporine A-based immunosuppression to FK506 for uncontrollable
      acute rejection (AR; n = 16), chronic rejection (n = 4), or predominantly
      nonspecific hepatitis (n = 3). Of these, 19 had received poly- or monoclonal anti
      T lymphocyte antibodies either for AR prophylaxis or therapy before FK506
      conversion. Full clinical and histologic responses to FK506 therapy were observed
      in 11/16 cases of AR compared with 0/7 cases of non-AR indications (P = 0.006).
      Acute FK506 toxicity included renal dysfunction in 12/23 children (52%),
      neurological disorders in 7/23 (30%), and isolated hyperkalemia in 2/23 (9%),
      with a poor correlation with the corresponding FK506 trough plasma level.
      Moreover, a significant impairment of glomerular filtration rate was recorded in
      the 12 children who received FK506 treatment for more than 6 months (P = 0.002).
      FK506 therapy had to be definitively withdrawn in 6 cases (fatal infections: n =
      4; persistent tremor: n = 1; reason unrelated to FK506: n = 1). Five children
      developed a lymphoproliferative syndrome (LPS), leading to death in 3 cases
      despite cessation of the immunosuppressive therapy; in the other 2 patients, LPS
      was controlled, and the children were successfully retransplanted for chronic
      rejection under FK506. The occurrence of Epstein-Barr virus primary infection
      under FK506 therapy was found to constitute a significant risk factor for LPS (P
      = 0.027). In summary, full response to FK506 conversion was observed in 69% of
      uncontrollable AR cases; however, 74% and 22% of this probably over
      immunosuppressed population experienced major adverse events and LPS under FK506
      therapy, respectively.

PMID- 7507273
TI  - Nitric oxide: significance for the gastroenterologists.

PMID- 7507274
TI  - Responsiveness of basophil granulocytes of horses suffering from chronic
      obstructive pulmonary disease to various allergens.
AB  - As basophils are the major effector cells of allergic reactions, confirmation of
      the allergic etiology of chronic obstructive pulmonary disease (COPD) was sought
      by the demonstration of a specific in vitro response of equine basophilic blood
      cells to some potential allergens (Aspergillus, Cladosporidium, Mucor,
      Penicillium, extracts of dust particles of hay and straw). The allergen induced
      degranulation of basophils and the histamine and protease release from basophils
      during incubation with the allergens were tested. By evaluating the results
      obtained from 14 COPD horses and eight controls it could be shown that the
      sensitivity of the basophils of affected horses was increased, particularly
      against the allergen extract of Mucor mucedo and Mucor spinosus. Further a
      greater percentage of COPD horses reacted positively with the Mucor allergen
      extract. The mitogenic stimulation of lymphocytes by PHA and by the allergen
      extracts used gave comparable results in affected and control horses. Thus the in
      vitro stimulation of basophils may be an easily to perform testing device for the
      identification of potential allergens involved in the pathogenesis of equine
      COPD.

PMID- 7507275
TI  - Porcine leukocyte interferon exhibits close antigenic relatedness to human
      interferon alpha 2, but not to human interferon alpha 1.
AB  - As reported by others using polyclonal antisera, natural human and porcine
      interferons (IFN)-alpha are antigenically related. Using monoclonal antibodies
      (mAb) in neutralization and ELISA experiments, we found differences in the
      subtype/antigenic composition between virus-induced porcine and human leukocyte
      preparations. Human leukocyte IFN-alpha contains two major antigenically distinct
      subtypes, IFN-alpha 1 and IFN-alpha 2. However, swine leukocytes produced only a
      single predominant species of IFN-alpha with high antigenic homology to human IFN
      alpha 2. Moreover, we were unable to detect close antigenic relatedness between
      recombinant porcine and human IFN-alpha 1 subtypes.

PMID- 7507276
TI  - Morphometry of peroxisomes and immunolocalization of peroxisomal proteins in the
      liver of patients with generalised peroxisomal disorders.
AB  - Hepatic peroxisomes were studied by morphometric and immunocytochemical
      techniques in control patients and in four Zellweger syndrome patients, two
      infantile Refsum's (IRD) patients, one neonatal adrenoleukodystrophy (NALD)
      patient, and three patients with peroxisomal disorders (PD) which do not fit any
      currently recognised classification, but have disorders involving a defect in
      peroxisomal biogenesis. Peroxisomes which were ultrastructurally abnormal and
      greatly reduced in size and/or number were found in two of the Zellweger syndrome
      patients, and the NALD and IRD patients. There was variation in their numerical
      density ranging from none at all in two of the Zellweger syndrome patients to
      normal numbers in the IRD patients. In most patients there was a decrease in the
      immunolabelling of catalase over the peroxisomes. In the Zellweger syndrome and
      NALD patients, the small, abnormal peroxisomes did not label for any of the beta
      oxidation proteins. The IRD patients and the PD patients however, were
      heterogeneous with respect to beta-oxidation labelling. The ultrastructural
      heterogeneity of peroxisomes in these peroxisomal disorders patients indicates
      there may be genotypic differences between the major groups and also within each
      group. The common factor in all the patients in this study where peroxisomes were
      present was the presence in the hepatic peroxisomes of an electron dense centre
      which did not label immunocytochemically for catalase or the beta-oxidation
      enzymes. This electron dense centre may indicate a structural abnormality in the
      peroxisomes in these patients.

PMID- 7507277
TI  - The morphological substrate of autonomic regulation of the bronchial epithelium.
AB  - Observations of explanted bronchial mucosa show that ciliary function is
      maintained for 7 days subsequent to explanation. This finding demonstrates that
      non-neural mechanisms exist which regulate ciliary function. Ultrastructural and
      immunohistochemical studies both for light and electron microscopy were performed
      on human bronchial biopsy material and lung resection specimens in order to
      recognize the morphological substrate of this regulatory mechanism. A complex
      system of cytokeratin filaments and microtubules radiate through the whole
      cytoplasm of ciliated cells with direct contact to the nucleus, cilia,
      microvilli, desmosomes and to the apical terminal adhesive complex. Between the
      basal bodies and the apical terminal adhesive complex microfilaments can be
      found. In the apical cytoplasm a dense filamentary network is seen in association
      with the adhesive complex. These morphological findings indicate that the
      cytoskeleton of the bronchial epithelium plays a key role in the co-ordination of
      ciliary function.

PMID- 7507278
TI  - Prostate specific antigen and prostate specific acid phosphatase in
      adenocarcinoma of Skene's paraurethral glands and ducts.
AB  - An autopsy case of adenocarcinoma of Skene's paraurethral gland co-incident with
      renal cell carcinoma is described. The adenocarcinoma showed distinct prostate
      specific antigen and prostate specific acid phosphatase pointing to the
      equivalence between the male prostate and Skene's paraurethral glands and ducts.
      Skene's gland are the homologue of the prostate in females and tumours arising
      from them are immunohistochemically similar to male prostate carcinoma.

PMID- 7507279
TI  - Expression of infectious pancreatic necrosis virus polyprotein and VP1 in insect
      cells and the detection of the polyprotein in purified virus.
AB  - In order to study the molecular biology of infectious pancreatic necrosis virus
      (IPNV) replication, six different recombinant baculoviruses were constructed. The
      following four recombinants contained genome segment A-specific sequences; (i)
      AcPP contained the complete polyprotein coding region and Spodoptera frugiperda
      (Sf) cells infected by these recombinants synthesized the 106-kDa polyprotein
      (NH2-preVP2-NS protease-VP3-COOH), which was only partially processed by the
      protease to yield preVP2 and VP3 and unprocessed polyprotein; (ii) AcPP(S) and
      AcPP(Ss) represented 3' truncated sequences of the segment A cDNA where the VP3
      coding region and that coding for 30 and 98 carboxy terminal amino acids of NS in
      the two constructs, respectively, were deleted. AcPP(S) demonstrated partial, and
      that of AcPP(Ss), complete loss of proteolytic activity, demonstrating that the
      carboxy one-third of the 29-kDa NS protease is necessary for the formation of the
      active enzyme; and (iii) AcPP(B/B) contained all but the first 180 nt of the pVP2
      gene, the complete NS coding region, and the amino end of VP3. Analysis of cells
      coinfected with AcPP(Ss) and AcPP(B/B) showed either that the protease did not
      work in trans or that the alteration of the structure of the substrate prevented
      cleavage. Recombinant baculoviruses AcVP1VL and AcVP1ETL contained IPNV genome
      segment B cDNA encoding the 94-kDa VP1 which is the viral RNA-dependent RNA
      polymerase. AcVP1VL contained the whole segment B cDNA, whereas in AcVP1ETL, the
      5' non-coding sequences were deleted resulting in the production of large amounts
      of VP1 when Sf cells were infected with this recombinant. The use of recombinants
      AcPP and AcVP1ETL as well as monoclonal antibodies and VP1-specific sera allowed
      the unambiguous identification of the high molecular weight minor polypeptides
      present in purified IPNV demonstrating the presence of both VP1 and the
      polyprotein in purified virus preparations.

PMID- 7507280
TI  - Chimeric parvovirus B19 capsids for the presentation of foreign epitopes.
AB  - Chimeric proteins consisting of the VP2 capsid protein of human parvovirus B19
      and defined linear epitopes from human herpes simplex virus type 1 and mouse
      hepatitis virus A59 inserted at the N-terminus and at a predicted surface region
      were expressed by recombinant baculoviruses. The chimeric proteins expressed the
      inserted epitopes and assembled into empty capsids. Immunoelectron microscopy
      indicated that the epitopes inserted in the loop were exposed on the surface of
      the chimeric particles. The chimeric capsids were immunogenic in mice and
      antibodies specific for the inserted sequences were induced. In the case of MHV,
      antibodies were produced that recognized the epitope in the context of native
      virus. Mice immunized with the chimeric capsids were partially protected against
      a lethal challenge infection with either MHV or HSV.

PMID- 7507281
TI  - Conserved determinants for CD4+ T cells within the light chain of the H3
      hemagglutinin molecule of influenza virus.
AB  - Helper T-cell clones were isolated from BALB/c mice that had been inoculated with
      purified light chain (HA2) from H3 subtype influenza virus hemagglutinin (HA).
      The clones were divided into two distinct groups based on their ability to
      proliferate in response to bromelain-derived HA (BHA) and the light chain derived
      from it (BHA2), both of which lack the C-terminal 46 amino acid residues of the
      HA2 chain. The first group contained two I-Ad restricted clones that proliferated
      in response to BHA and BHA2 and were found to recognize the determinant
      96AELLVALEN104. The remaining seven clones were I-Ed restricted, required intact
      HA2 for proliferation, and responded to synthetic peptides containing the
      sequence 170RFQIKGVEL178 which spans the bromelain cleavage site. Although all T
      cell clones proliferated in response to a wide range of different H3 virus
      strains, they showed no cross-reactivity with viruses of the H1 or H2 subtype.
      The T-cell clones from each group were able to provide help to virus-primed B
      cells allowing them to produce anti-HA antibody in vitro.

PMID- 7507282
TI  - Loss of conserved cysteine residues in the attachment (G) glycoprotein of two
      human respiratory syncytial virus escape mutants that contain multiple A-G
      substitutions (hypermutations).
AB  - Two escape mutants (R10c/1 and R10c/10) of the human respiratory syncytial (RS)
      virus Long strain were selected after serial passage in the presence of
      monoclonal antibody c793 directed against the G glycoprotein. This antibody
      recognizes an epitope which is shared by all viruses of the two antigenic
      subgroups in which human RS virus isolates have been subdivided. The mutant
      viruses had lost most of the G protein conserved and subgroup-specific epitopes
      but maintained the strain-variable epitopes. The two mutants had 10 or 11
      nucleotide changes in the central region of the G protein gene when compared to
      the Long sequence, and almost all of those changes were different between the two
      mutants. The majority of the nucleotide changes involved A-G transitions (U-C in
      the positive sense) that resulted in amino acid substitutions. Each mutant had a
      total of six amino acid changes, and the changes were different between the two
      mutants. Unexpectedly, each mutant lost one of the four conserved cysteines of
      the G protein, and a different cysteine (Cys 182 or 186) was lost in each mutant.
      They are, in fact, the first reported RS viruses with only three cysteines in the
      G protein ectodomain. The genetic mechanism that generated the escape mutants and
      its relevance for the natural history of RS virus are discussed.

PMID- 7507285
TI  - [Immune mechanisms of atopic dermatitis].
AB  - The syndrome of atopy consists of three major clinical entities, i.e., allergic
      rhinoconjunctivitis, allergic asthma and atopic dermatitis, and is usually
      associated with elevated serum IgE levels. Whereas the pathogenetic role of IgE
      is clearly established in the case of allergic rhinoconjunctivitis and allergic
      asthma, the occurrence of atopic dermatitis cannot be easily explained by
      hyperimmunoglobulinemia E. Atopic dermatitis clinically presents as
      eczematization of certain predisposed (mostly flexural) areas of the skin. The
      clinical and histopathological picture, as well as the emergence kinetics of
      atopic eczema, roughly follow the criteria of delayed type (type IV) immune
      reactions. It is at present unclear whether the type I-like and the type IV-like
      allergic reactions of atopy are events occurring independently of each other or,
      alternatively, are pathogenetically linked to each other. Recent data suggest
      that in contrast to allergic contact dermatitis where Th 1-like T cells producing
      interleukin (IL)-2 and interferon (IFN)-gamma are the cells eliciting the
      lesions, the cellular infiltrate of atopic dermatitis lesions is dominated by Th2
      cells capable of producing IL-4 and IL-5. Consequently, two clinical findings of
      atopic disorders are explicable by the observed Th2 cytokine secretion pattern
      i.e. i) the hypereosinophilia by the hyperproduction of IL-5 and ii) the
      hyperimmunoglobulinemia E, for which the presence of IL-4 is a "conditio sine qua
      non".(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507284
TI  - CD4 mRNA expression in CD19-positive B cells and its suppression by the Epstein
      Barr virus.
AB  - We have examined for synergy between the IIIB strain of HIV-1 and Epstein-Barr
      virus (EBV) during infection of a homogeneous cell type. In order to obtain a
      cell population consisting of a homogeneous cell type, CD19-positive B
      lymphocytes were purified from human tonsils by flow cytometry. CD19-positive
      lymphocytes did not express detectable surface CD4 antigen. However, CD4 mRNA
      could be detected in CD19-positive lymphocytes by reverse transcription coupled
      to polymerase chain reaction and by dot blot hybridization using an antisense
      riboprobe. Transcription of CD4 mRNA in CD19-positive lymphocytes was suppressed
      by infection with the B95-8 strain of EBV and lost in B95-8-transformed
      lymphoblastoid cell lines. In contrast, the P3HR-1K strain of EBV had no effect
      on the level of CD4 mRNA. HIV-1 could infect CD19-sorted B cells as measured by
      accumulation of reverse transcriptase and syncytia induction after coculture with
      SupT1 cells. HIV-1 infection of CD19-bearing lymphocytes was blocked by OKT4a
      antibodies. The ability of HIV-1 to replicate in CD19-positive B lymphocytes
      declined following preinfection with B95-8 but not with P3HR-1K. These results as
      well as results with an EBNA-2 expression vector suggest that down-regulation of
      both CD4 mRNA and HIV-1 infection in human B cells is a function of EBV nuclear
      antigen EBNA-2. The fact that native CD19-positive B lymphocytes express
      sufficient CD4 receptor mRNA to allow HIV-1 infection strengthens the possibility
      that HIV-1 replication in B cells directly participates in AIDS pathogenesis. In
      addition, infection with EBV may modulate the ability of HIV-1 to infect and
      establish a latent infection in B lymphocytes in co-infected individuals.

PMID- 7507283
TI  - Design and construction of rhinovirus chimeras incorporating immunogens from
      polio, influenza, and human immunodeficiency viruses.
AB  - This paper describes the design and construction of chimeric human rhinoviruses
      that contain immunogenic regions from other pathogens as part of their surface
      coat proteins. Segments encoding the poliovirus 3 Sabin VP1 and VP2 proteins, the
      influenza hemagglutinin (HA) glycoprotein, and the human immunodeficiency virus
      gp120 surface and gp41 transmembrane glycoproteins were inserted into a full
      length clone of human rhinovirus 14 (HRV14) at regions corresponding to
      neutralizing immunogenic sites IA (NIm-IA) and II (NIm-II). Of 12 chimeric
      constructs described, 3 produced viable virus. An HRV14 chimeric virus containing
      five amino acids of influenza HA (corresponding to 300 A2 of solvent-accessible
      surface area) had wild-type HRV14 growth characteristics and was neutralized by
      four of four anti-influenza HA antisera with reciprocal neutralizing titers
      ranging from 180 to 330. However, antisera raised in two guinea pigs against the
      HRV14:influenza HA chimera did not show significant neutralization of relevant
      strains of influenza. These results are the first to demonstrate the feasibility
      of making viable chimeras of human rhinoviruses displaying heterologous
      immunogens.

PMID- 7507286
TI  - [Molecular and functional characterization of allergens: fundamental and
      practical aspects].
AB  - Well-defined allergens are a prerequisite for the exact diagnosis and
      immunotherapy of Type I (IgE-mediated) allergic diseases. The allergens have to
      be available in highly purified form and in sufficient quantities. By applying
      molecular cloning methods this goal can be achieved with respect to both
      characterization and reproducibility of allergen preparations. Moreover, this
      technique leads to the deduction of primary structures of allergens, which allows
      computer-aided comparisons with already known amino acid sequences. Significant
      sequence similarities with well-described proteins may point to a biological and
      biochemical function of the cloned allergen. The major allergen of white birch,
      Bet v 1, and its close relatives from alder, hazel, and hornbeam belong to a
      family of pathogenesis-related proteins ubiquitous in angiosperms. Based on these
      results, a percentage of food intolerance can now be regarded as Type I allergy
      due to Bet v 1-related proteins. By sequence comparisons, Bet v 2, another birch
      pollen allergen, was identified as the ubiquitous cytoskeleton-associated
      protein, profilin. For its high sequence conservation and its ubiquitous
      appearance in allergenic sources of plant origin, profilin was shown to represent
      a pan-allergen. Recombinant non-fusion Bet v 1 revealed identical immunological
      properties with respect to interaction with both antibodies and Bet v 1-specific
      T cell clones when compared with natural Bet v 1 purified from birch pollen.

PMID- 7507287
TI  - [Outpatient diuretic treatment of terminal heart failure by a completely
      implantable venous infusion system].
AB  - In severe heart failure with peripheral and enterohepatic congestion resistance
      to diuretics with inactivation of oral furosemide is a common finding. Impaired
      bioavailability is most likely related to pharmacodynamic and especially to
      pharmacokinetic reasons. To ensure efficient drug delivery and effective
      treatment with diuretics, venous access devices (port-systems) were implanted in
      10 patients (eight men and two women, age between 57 and 80 years). All patients
      were in heart failure functional class III-IV and had a history of recurrent
      episodes of severe decompensation; none was suitable for heart transplantation.
      Injections of furosemide and other drugs were performed 1-4 times a day; one
      female patient performed the intravenous injections herself, in three cases the
      partners and in six cases the practitioner or an outpatient nurse performed the
      injections. All patients were treated on an outpatient basis, i.e., at home or in
      nursing homes. The port-implantation was followed up between 30 and 742 days (1
      24 months); no serious complications were observed. Both patients and their
      partners were considered to well tolerate and accept the port-systems. Totally
      implantable venous access devices promise to reduce the number and severeness of
      cardiac decompensations in chronic preterminal heart failure by application of
      daily intravenous furosemide. This form of outpatient treatment will ameliorate
      the quality of life and stabilize the course of these severely and chronically
      ill patients.

PMID- 7507288
TI  - Rapid assessment of Diff-Quik-stained pancreatic aspirates. A retrospective study
      of 40 intraoperative fine needle aspiration consultations, with measurement of
      nuclear size of look-alike small tissue fragments by image analysis.
AB  - Pancreatic cytomorphology based on Papanicolaou-stained smears has been studied
      extensively; however, studies on Diff-Quik-stained pancreatic smears are rather
      limited. Air-dried, Diff-Quik-stained smears lack crisp nuclear details, the
      cells are flattened on the slides, and the nuclei appear large and
      hyperchromatic. Between January 1988 and June 1992, 40 cases of intraoperative
      pancreatic fine needle aspirates were assessed by Diff-Quik stain. The objective
      of this study was to find practical clues applicable to the rapid and accurate
      assessment of Diff-Quik-stained pancreatic aspirates for intraoperative
      consultations. All cases were reviewed and correlated with histopathology. In
      particular, three cases that proved to be adenocarcinoma on subsequent frozen
      section but were not so diagnosed during intraoperative fine needle aspiration
      evaluation were analyzed. The nuclear sizes of small tissue fragments with
      overlapping nuclei, including three cases of normal pancreatic acini (mean
      diameter, 0.98, 1.17 and 1.04 x RBCs; coefficient of variation, 0.53, 0.83 and
      0.62 x RBCs), 2 cases of islet cell tumor (mean diameter, 1.19 and 1.32 x RBCs;
      coefficient of variation, 1.88 and 1.4 x RBCs) and 3 cases of adenocarcinoma
      (mean diameter, 1.55, 1.86 and 1.72 x RBCs; coefficient of variation, 1.5, 1.7
      and 1.9 x RBCs) were obtained with an image analyzer. The adjacent RBCs served as
      internal size controls. In Diff-Quik-stained, air-dried smears we relied on the
      accurate identification of pancreatic acini, which had the same size as the
      adjacent RBCs. Islet cell tumors had slightly larger nuclei, which were much more
      variable in size. The nuclei of adenocarcinoma were much larger than the
      surrounding RBCs and also showed marked variation in size. The composition of the
      pancreatic aspirate is important: ductal epithelium predominates in ductal
      carcinoma, and acini predominate in pancreatitis.

PMID- 7507290
TI  - Vital staining indicating cell migration towards the periphery in the growth
      plate. Studies of fibular heads in rabbits.
AB  - In 38 fibular heads of young rabbits the germinal layer of the growth plate was
      traversed perpendicularly to the axis of the bone with an injection needle. The
      resulting channel was packed with pieces of raw agar-agar carrying Nile blue
      sulfate dye. The rabbits were killed after 1-8 days. In frozen sections of the
      fibular heads, stained cells were scattered over the germinal layer; in 19 of the
      plates a row of distinctly stained cells reached from the periphery of the
      germinal layer to the borderline of the innermost corner of the ossification
      groove of Ranvier (1889). Our results strengthen the view that the cells forming
      the periosteal bone originate in the growth plate, with implications for the
      pathogenesis of diseases of the growing skeleton.

PMID- 7507289
TI  - Trilineage response in severe aplastic anemia following long-term therapy with
      recombinant human granulocyte colony-stimulating factor.
AB  - We investigated the effects of long-term therapy with recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) in a 69-year-old man with severe
      aplastic anemia (SAA). The patient was too old to receive a bone marrow
      transplantation, and high-dose methylprednisolone and antilymphocyte globulin
      were ineffective. We administered rhG-CSF in combination with metenolone acetate.
      Trilineage blood cell components were recovered 6 months later. These findings
      suggest that long-term G-CSF therapy may be beneficial in patients with SAA who
      are not candidates for bone marrow transplantation.

PMID- 7507291
TI  - Relationship between follicular fluid levels of insulin-like growth factor
      binding protein-1 and sex steroids from normal human ovarian follicles.
AB  - The aim of this study was to examine the possible correlations between follicular
      fluid insulin-like growth factor binding protein 1 (IGFBP-1) and follicular fluid
      and serum parameters of granulosa cell function. Twenty-six subjects undergoing
      diagnostic laparoscopy for infertility had follicular fluid samples collected.
      Subjects were aged 20-42 years, were having regular ovulatory cycles and either
      had tubal disease or a partner with male factor infertility. Sex steroids,
      insulin-like growth factor 1 (IGF-1) and IGFBP-1 were measured by
      radioimmunoassay. Follicular fluid levels of IGFBP-1 were significantly
      correlated with levels of estradiol, progesterone in follicular fluid and with
      serum IGFBP-1 levels, and negatively correlated with follicular fluid
      androstenedione levels. These results suggests that IGFBP-1 may have a role in
      the regulation of human ovarian follicles.

PMID- 7507292
TI  - Developmental data on individuals with the Brachmann-de Lange syndrome.
AB  - One hundred twenty-two patients with clinically confirmed Brachmann-de Lange
      syndrome (BDLS) were evaluated developmentally. Recruitment was made from our
      genetics department and through meetings of the Cornelia de Lange Syndrome
      Foundation parent support group. Developmental information was obtained from
      records of physicians, schools and developmental centers, or from parents on each
      of the 122 individuals, allowing division into four groups for study: group 1 (n
      = 48) underwent formal developmental assessments, which generated intelligence or
      developmental quotients, and had a completed parental questionnaire with specific
      developmental questions regarding ages of skills mastered; group II (n = 23) had
      additional developmental records available without formal testing, as well as the
      questionnaire; group III (n = 22) had only a completed questionnaire; and group
      IV (n = 29) had formal developmental testing or other developmental records but
      no available questionnaire. These data were analyzed in order to be able to
      predict attainable psychomotor development. Average scores on formal testing were
      found to be in the mild to moderate level of mental retardation, ranging from
      below 30 to 85, with an average intelligence quotient of 53, higher than
      previously reported. Visual-spatial memory and perceptual organization skills
      were found to be strengths. Younger individuals born before 1980 demonstrated
      higher scores on testing. Early intervention appears to play a major role in the
      level of developmental achievement.

PMID- 7507293
TI  - Intrafamilial variability in Hurler syndrome and Sanfilippo syndrome type A:
      implications for evaluation of new therapies.
AB  - Intrafamilial variability has not been reported previously in Hurler syndrome or
      Sanfilippo syndrome type A. We describe two families in which sibs with
      comparable deficiencies of alpha-iduronidase (Hurler) or sulfamidase (Sanfilippo
      type A) activities in vitro nonetheless have divergence in clinical severity and
      disease progression. These cases underscore the need for caution in counseling as
      well as the limitations of using sibs as controls in evaluating the outcome of
      treatment.

PMID- 7507295
TI  - Mild Brachmann-de Lange syndrome. Phenotypic and developmental characteristics of
      mildly affected individuals.
AB  - Since 1981, we have identified 3 patients with mild Brachmann-de Lange syndrome
      (BDLS) who have had subtle but definite manifestations of the syndrome and mild
      effects on growth and development. J.G. (B.D. 12/9/72) was first examined at 20
      months. He had rather typical craniofacial findings and hirsutism, limitation of
      full supination of his arms, and brachyclinodactyly of the 5th fingers. IQ was
      estimated at 65. K.H. (B.D. 10/10/83) was first examined by us at age 9 months
      and was diagnosed as having "mild" BDLS. At age 5, K.H. has demonstrated
      relatively normal cognitive development (low average-average IQ of 74) with
      specific learning problems: weakness of visual-motor skills, delayed expressive
      language development, and articulation difficulties. At age 7, he was attending a
      regular 1st grade classroom, with some special education assistance. M.E. (B.D.
      4/19/78) was diagnosed at age 10 years as having "mild" BDLS. His physical
      changes were more subtle than those of the 2 patients above. At age 10, M.E. was
      in the regular 4th grade classroom receiving special education support. His IQ
      was in the borderline-low-average range. He had strengths in rote verbal skills,
      with weaknesses in reading and writing. These 3 patients demonstrate mild BDLS in
      which characteristic manifestations of the syndrome, particularly craniofacial
      anomalies, are present and recognizable, but quite subtle, thus making the
      clinical diagnosis difficult. In addition, the milder physical phenotype is
      associated with milder cognitive and behavioral consequences.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7507294
TI  - Mild Brachmann-de Lange syndrome. Delineation of the clinical phenotype, and
      characteristic behaviors in a six-year-old boy.
AB  - Brachmann-de Lange syndrome (BDLS) is a rare multiple congenital anomaly/mental
      retardation (MCA/MR) syndrome with variable expression, making diagnosis of mild
      cases difficult. The most consistent manifestations appear to be the
      characteristic face, which can be subtle in children who are mildly affected
      [Ireland and Burn, 1991: Twelfth Annual David W. Smith Workshop on Malformations
      and Morphogenesis]. Other aspects of the syndrome include variable degrees of
      mental retardation, growth retardation, structural abnormalities of the limbs,
      and behavior abnormalities, noted to be "autistic" [Jones, 1988: "Smith's
      recognizable patterns of human malformation"]. Johnson et al. [1976: Pediatr Res
      10:843-850] described a behavior phenotype felt to be common in patients with
      BDLS. They predicted that patients with BDLS may respond to "behavioral
      intervention". Other behavior abnormalities in BDLS have been reported [Barr et
      al., 1971: Neuropadiatrie 3:46-66; Hawley et al., 1985: Am J Med Genet 20:453
      459]. We report on a 6-year-old boy with the facial characteristics of BDLS,
      normal birth weight, prenatal onset of a small head relative to length, postnatal
      onset growth deficiency, nearly normal psychomotor development with onset of
      clear developmental delays by 2 years. He developed behavior problems similar to
      those seen in other patients with BDLS. These behaviors are most consistent with
      Pervasive Development Disorder-NOS (PDD), and Autistic Disorder [DSM-III-R, 1987]
      which encompasses a spectrum of mild to severe autistic behaviors. We report
      successful in-patient care utilizing medical and behavioral techniques to reduce
      the frequency of the behaviors. We feel that the presence of the characteristic
      behaviors may be helpful in confirming the diagnosis of BDLS.

PMID- 7507296
TI  - Dup(1q)(q42-->qter) syndrome: case report and review of literature.
AB  - We report on a patient with primordial growth retardation, mental retardation,
      and minor anomalies (triangular face, open sagittal suture, frontal bossing,
      telecanthus, upturned nose, micrognathia, and small mouth with downturned
      corners). The diagnosis of Russell-Silver syndrome (RSS) had been considered but
      was abandoned when cytogenetic evaluation showed a partial trisomy 1q or
      duplication 1q (46,XY,15, + der(15)t(1;15)(q42;qter). Data from another 5 reports
      of dup(1)(q42-->qter) do not allow delineation of a typical syndrome. However,
      individuals with dup(1q), del(15q), and Russell-Silver syndrome share common
      manifestations (i.e., low birth weight, growth retardation, triangular face, low
      set/abnormal ears, micrognathia, renal anomalies.

PMID- 7507298
TI  - Effects of interleukin-3 with or without the c-kit ligand, stem cell factor, on
      the survival and cytoplasmic granule formation of mouse basophils and mast cells
      in vitro.
AB  - We assessed the ultrastructure and the cell-surface expression of receptors for
      immunoglobulin E (Fc epsilon R), and c-kit, the receptor for stem cell factor
      (SCF), in mouse basophils and mast cells present in short-term cultures of mouse
      bone marrow cells in interleukin-3 (IL-3) with or without SCF. Basophils did not
      develop increased numbers of cytoplasmic granules and underwent apoptosis in
      cultures containing IL-3 and SCF, whereas mast cells thrived and developed
      increased numbers of granules. Basophils were nearly all Fc epsilon R+ c-kit-
      when sorted after culture in IL-3 and SCF; most mast cells were Fc epsilon R+ c
      kit+. However, a second population of Fc epsilon R+ c-kit- mast cells was present
      after culture in IL-3 and SCF. These c-kit receptor-negative mast cells were less
      mature than c-kit+ mast cells and contained significantly fewer cytoplasmic
      granules than the c-kit+ mast cells present in the same cultures (P < 0.001).
      Thus, mouse basophils express little or no c-kit receptor on their surface, nor
      can they survive for long periods in SCF-supplemented cultures. By contrast,
      mouse mast cells seem to express the Fc epsilon R early in their development,
      even before they express detectable c-kit receptors on their surface. IL-3
      promotes cytoplasmic granule formation in immature mast cells, but even more
      granules are formed when c-kit receptor-positive immature mast cells are cultured
      in both SCF and IL-3.

PMID- 7507299
TI  - CD40 expression in Hodgkin's disease.
AB  - CD40 is a transmembrane protein that belongs to a superfamily of proteins related
      to nerve growth factor receptor. CD40 is expressed on B cells and some B cell
      malignancies. It appears to be involved in B cell proliferation and the
      prevention of apoptosis in germinal center cells, which is accompanied by
      expression of bcl-2. Its expression is up-regulated by the EBV protein latent
      membrane protein-1 and cytokines interleukin-4 and interferon-gamma. The
      expression of CD40 in 37 cases of Hodgkin's disease and 23 cases of non-Hodgkin's
      lymphoma (11 T cell lymphomas and 12 B cell lymphomas) was examined by paraffin
      section immunohistochemistry using the BB-20 monoclonal antibody. In 26 of 37
      cases of Hodgkin's disease the Reed-Sternberg cells showed strong membrane or
      cytoplasmic expression of CD40. Only 3 of 23 non-Hodgkin's lymphomas showed any
      expression of CD40 and then only weakly. There was no correlation between
      expression of bcl-2 or latent membrane protein-1 with CD40 expression. These
      results show that there is probable hyperexpression of CD40 in Hodgkin's disease
      and suggest that dysregulation of CD40 expression may play a role in the
      pathogenesis of Hodgkin's disease.

PMID- 7507297
TI  - Increased expression of acidic and basic fibroblast growth factors in chronic
      pancreatitis.
AB  - Acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF)
      belong to a family of mitogenic polypeptides that are involved in cellular
      proliferation and differentiation. In this study we investigated the potential
      role of aFGF and bFGF in chronic pancreatitis (CP), a fibrotic condition
      associated with acinar cell dedifferentiation and atrophy, and fibroblastic
      proliferation. By immunohistochemistry, aFGF and bFGF were abundant in pancreatic
      ductal and acinar cells in pancreatic tissues from CP patients. Immunoblotting
      with the same highly specific monoclonal antibodies demonstrated a marked
      increase in aFGF and bFGF in pancreatic homogenates from CP patients by
      comparison with the normal pancreas. Northern blot analysis indicated that, by
      comparison with normal controls, 16 of 21 CP tissues exhibited a 14-fold increase
      in aFGF mRNA levels, and 19 of 21 CP tissues exhibited a 15-fold increase in bFGF
      mRNA levels. In situ hybridization confirmed that this overexpression occurred in
      ductal and acinar cells, and indicated that both mRNA moieties colocalized with
      their respective proteins. These findings suggest that aFGF and bFGF may either
      be involved in the pathobiological mechanisms that occur in CP, or that their
      overexpression may be the consequence of other perturbations that occur in this
      disorder.

PMID- 7507303
TI  - Prostate marker immunoreactivity in salivary gland neoplasms.

PMID- 7507301
TI  - Vascular origin of Kaposi's sarcoma. Expression of leukocyte adhesion molecule-1,
      thrombomodulin, and tissue factor.
AB  - We studied seven cases of Kaposi's sarcomas (KS) obtained from patients with AIDS
      and one KS from a patient without HIV infection. Antigen expression was studied
      by immunocytochemistry and mRNA expression by in situ hybridisation. The markers
      tested were endothelial leukocyte adhesion molecule-1, thrombomodulin, and tissue
      factor. In all tumors (AIDS and non-AIDS associated) these markers reacted
      positive, indicating transcription and translation of these genes in KS. The
      synthesis and expression of tissue factor and thrombomodulin suggests that KS is
      a tumor that has tissue factor-mediated thrombin formation under the control of
      thrombomodulin. The expression of thrombomodulin and endothelial leukocyte
      adhesion molecule-1 provides evidence for the vascular origin of KS.

PMID- 7507302
TI  - Detection of epidermal growth factor receptor mRNA in tissue sections from biopsy
      specimens using in situ polymerase chain reaction.
AB  - Human epidermal growth factor (EGF) receptor mRNA was detected in cryopreserved
      tissue sections adherent to whole glass slides using in situ reverse
      transcriptase polymerase chain reaction. EGF receptor cDNA was synthesized in
      situ by reverse transcription using an EGF receptor-specific oligonucleotide
      primer. In situ polymerase chain reaction amplification in the presence of
      digoxigenin-11-dUTP and subsequent binding with an antidigoxigenin antibody
      conjugated to alkaline phosphatase allowed direct visualization. Because DNase,
      RNase, or proteinase K are not required, tissue integrity is maintained. EGF
      receptor mRNA is expressed in the basal layer of normal human skin epithelium and
      is significantly overexpressed in squamous cell tumor specimens, which is
      consistent with conventional analysis of EGF receptor expression. The assay is
      semiquantitative, quicker, more sensitive, and void of the nonspecific binding
      associated with in situ hybridization. In situ reverse transcriptase polymerase
      chain reaction using whole glass slides is ideally suited for detecting moderate
      to infrequently expressed transcripts in biopsy specimens.

PMID- 7507300
TI  - Monocyte adhesion to endothelium in simian immunodeficiency virus-induced AIDS
      encephalitis is mediated by vascular cell adhesion molecule-1/alpha 4 beta 1
      integrin interactions.
AB  - Because the mechanisms associated with recruitment of monocytes to brain in AIDS
      encephalitis are unknown, we used tissues from rhesus monkeys infected with
      simian immunodeficiency virus (SIV) to examine the relative contributions of
      various adhesion pathways in mediating monocyte adhesion to endothelium from
      encephalitic brain. Using a modified Stamper and Woodruff tissue adhesion assay,
      we found that the human monocytic cell lines, THP-1 and U937, and the B cell
      line, Ramos, preferentially bound to brain vessels from monkeys with AIDS
      encephalitis. Using a combined tissue adhesion/immunohistochemistry approach,
      these cells only bound to vessels expressing vascular cell adhesion molecule-1
      (VCAM-1). Furthermore, pretreatment of tissues with antibodies to VCAM-1 or cell
      lines with antibodies to VLA-4 (CD49d) inhibited adhesion by more than 70%.
      Intercellular adhesion molecule-1 (ICAM-1)/beta 2 integrin interactions were not
      significant in mediating cell adhesion to the vasculature in encephalitic simian
      brain using a cell line (JY) capable of binding rhesus monkey ICAM-1. In
      addition, selectin-mediated interactions did not significantly contribute to cell
      binding to encephalitic brain as there was no immunohistochemical expression of E
      selectin and P-selectin in either normal or encephalitic brain, nor was there a
      demonstrable adhesive effect from L-selectin using L-selectin-transfected 300.19
      cells on simian encephalitic brain. These results demonstrate that using the
      tissue adhesion assay, THP-1, U937, and Ramos cells bind to vessels in brain from
      animals with AIDS encephalitis using VCAM-1/alpha 4 beta 1 integrin interactions
      and suggest that VCAM-1 and VLA-4 may be integral for monocyte recruitment to the
      central nervous system during the development of AIDS encephalitis.

PMID- 7507304
TI  - High-dose aprotinin reduces blood loss in patients undergoing total hip
      replacement surgery.
AB  - BACKGROUND: Aprotinin, a proteinase inhibitor, has been reported to reduce blood
      loss significantly during cardiac surgery. The mechanisms of this effect remain
      unclear. We studied the effect of aprotinin on blood loss and transfusion
      requirement during total hip replacement. Potential mechanisms of action and side
      effects also were investigated. METHODS: Forty patients scheduled for primary
      total hip replacement were randomized to receive, in double-blind fashion, either
      aprotinin given as a bolus of 2 x 10(6) kallikrein inactivator units (KIU)
      followed by an infusion of 5 x 10(5) KIU/h until the end of surgery or an
      equivalent volume of normal saline. Anesthesia and surgical techniques were
      standardized and systematic deep venous thrombosis prophylaxis was used. Peri-
      and postoperative blood loss and transfusion were measured. Fibrinolysis,
      coagulation pathways, and platelet function were assessed. Renal and hepatic
      function as well as the incidence of deep venous thrombosis also were assessed.
      RESULTS: Aprotinin reduced total blood loss from 1,943 +/- 700 ml to 1,446 +/-
      514 ml (P < 0.05). This reduction of blood loss occurred during surgery (P <
      0.05) and postoperatively (P < 0.001). Total amounts of blood transfused were 3.4
      +/- 1.3 units/patient in the control group and 1.8 +/- 1.2 units/patient in the
      aprotinin group (P < 0.001). The activated partial thromboplastin time was
      significantly prolonged by aprotinin immediately after surgery, at 50.6 +/- 12.4
      versus 32.3 +/- 4.6 s in control patients (P < 0.001), but results of the other
      coagulation tests were not different between the two groups. No side effects were
      observed in the aprotinin group. The incidence of deep venous thrombosis in the
      two groups was not significantly different. CONCLUSIONS: The use of high-dose
      aprotinin during total hip replacement results in a reduction in both blood loss
      and the amount of blood transfused. Aprotinin's mode of action, however, remains
      to be elucidated.

PMID- 7507305
TI  - Characterization of infiltrating CD4+ cells in atopic dermatitis using CD45R and
      CD29 monoclonal antibodies.
AB  - Tissue sections from the skin of patients with atopic dermatitis were
      investigated by means of hematoxylin-eosin staining, the avidin-biotin-peroxidase
      complex method, and double-labeling immunofluorescence using monoclonal
      antibodies to cell-surface antigens, including CD45R and CD29. In skin lesions of
      patients with atopic dermatitis, the epidermis was spongiotic and hyperplastic
      with little cellular infiltrate. Perivascular dermal infiltrate was significant
      and consisted primarily of mononuclear cells. The majority of the infiltrating
      mononuclear cells in the skin of patients with atopic dermatitis were CD4+ cells.
      Langerhans' cells were also increased in number. Furthermore, we investigated the
      subsets in the infiltrating CD4+ cells by double-labeling immunofluorescence
      using CD45R and CD29 monoclonal antibodies. Among the infiltrating CD4+ cells,
      CD4+CD29+ cells were dominant and CD4+CD45R+ cells were also present.

PMID- 7507306
TI  - Neuropeptidergic innervation of equine synovial joints.
AB  - Immunocytochemical analysis of equine synovial membranes revealed presence of
      several neuropeptides, including substance P (SP), neurokinin A, and neuropeptide
      Y, in nerves of the radiocarpal, middle carpal, and metacarpophalangeal (fetlock)
      joints. Within the subsynovium, these neuropeptides were located perivascularly,
      whereas in the fronds, only neuropeptide Y was restricted to the vessels of the
      synovial membrane. Only SP and neurokinin A were found in the intimal layer. The
      intimal layer of the metacarpophalangeal joint contained more SP-immunoreactive
      fibers than were observed in the intimal layer of the radiocarpal joint.
      Substance P also was detected in the synovial fluid from all 3 joints, but mean
      +/- SD concentrations were significantly different only between the middle carpal
      joint (37.56 +/- 5.48 fmol/ml; n = 6) and the metacarpophalangeal joint (55.80 +/
      8.33 fmol/ml; n = 5) and between the middle carpal joint and the radiocarpal
      joint (52.43 +/- 14.60 fmol/ml; n = 7).

PMID- 7507307
TI  - Prostakath in urinary outflow obstruction.
AB  - Prostatic stents are a new method in the treatment of urinary outflow obstruction
      caused by benign prostatic hyperplasia. In this study the usefulness of the
      PROSTAKATH urospiral was evaluated in a multicenter study for treatment of
      urinary outflow obstruction. There were 87 males with problems related to
      urination. Sixty-eight patients had total retention. The mean functioning time of
      the spiral was nine (1-35) months. The outflow obstruction was cleared in 69
      (81%) patients. During follow-up, 33 spirals (39%) were removed; 15 of them
      within a few days after insertion. Altogether, transurethral resection of the
      prostate (TURP) was done on 22 patients, and transurethral incision of the
      prostate (TUIP) on four patients. Chronic urinary tract infection reduced
      significantly (P < 0.05) the functional time of the spiral; no other factors had
      influence on this variable. The spiral is a good alternative for treating urinary
      retention in patients waiting for prostatic surgery. The spiral may also be
      useful in the treatment of urinary obstruction caused by prostatic cancer.
      Recurrent vesical neck contracture can be prevented with the spiral. Entirely
      bedridden and demented patients do not benefit from this form of treatment.

PMID- 7507308
TI  - Efficacy and safety of bladder neck incision in patients with benign prostatic
      hyperplasia.
AB  - A prospective series of 104 patients underwent bladder neck incision (44
      unilateral and 60 bilateral) for urinary obstruction caused by a small benign
      prostate enlargement. The preoperative mean peak flow value improved
      significantly from 11.4 ml/s to 16.2 ml/s. There were no significant differences
      in peak flow values between the unilateral and bilateral incision groups.
      Subjective results seemed to be similar but transurethral resection of the
      prostate was needed more often after unilateral incision than after bilateral
      incision. Postoperative complications were recorded only in the bilateral
      incision group. Altogether 62% of the patients reported changes in erection or
      ejaculation ability. Bladder neck incision seems to be an effective means of
      treating urinary obstruction but adverse effects on sexual function are common,
      which should be kept in mind when offering this treatment to sexually active men.
      It can be regarded as the treatment of choice for older men with infravesical
      obstruction caused by a small prostate enlargement.

PMID- 7507309
TI  - Serum acid phosphatase in TUR syndrome.
AB  - The value of serum acid phosphatase (S-ACP) as a marker of transurethral
      resection (TUR) syndrome was studied in 105 patients undergoing TURP. In ten
      patients who developed TUR syndrome the elevation of S-ACP was statistically
      significantly higher than in the rest of the patients. In seven patients
      prostatic cancer was diagnosed in the resection chips, but there were no
      differences in the S-ACP levels during TURP between these patients and the rest
      of the group. According to the present study, S-ACP seems to be a reliable and
      cheap marker of TUR syndrome, but the method is slow as compared to ethanol,
      which restricts its use.

PMID- 7507310
TI  - [Forum on tissue expansion. Neovascularization of skin flap from expanded
      anatomical arteriovenous pedicle. An initial experimental study].
AB  - The purpose of this study is to demonstrate the development of angiogenesis
      spreading from a vascular pedicle stretched by an expander, and to determine its
      potential to supply blood to an adjacent skin area. In the pig model (9 animals),
      we inserted an expander under the saphenous vessels after interrupting all the
      connections between the pedicle and the related inguinal skin. The opposite side
      was used as a control with a non-expanded silicone sheet, 1 mm (2 animals) and 3
      mm (7 animals) thick. After 6 weeks of expansion, vascular island skin flaps were
      elevated on the saphenous vessels. 6 out of 7 expanded flaps were totally
      successful. Of the 5 flaps elevated above the 3 mm silicone sheet, 1 flap was
      successful and 4 partially failed. The 2 flaps elevated above the 1 mm silicone
      sheet failed. An anatomical arteriovenous pedicle stretched by an expander can
      supply a skin area located distal to it. Angiogenesis also occurs in contact with
      a thick silicone sheet but the blood supply of the skin is less effective. The
      newly formed vascular network is visualized on the angiograms.

PMID- 7507311
TI  - Hemoglobin variant detection from dried blood specimens by high performance
      liquid chromatography.
AB  - The convenience of dried blood filter paper specimens for genetic screening
      programs has prompted us to test the stability of these specimens for hemoglobin
      identification by cation exchange high performance liquid chromatography. This
      report shows that identification of Hb AA, Hb AF, Hb AS, Hb FAS, Hb AJ, Hb FJ, Hb
      EF, and Hb SS can be achieved by high performance liquid chromatography even
      after six weeks of storage at room temperature. Also, accurate hemoglobin
      quantitation can be obtained from the same samples within three weeks of storage
      at room temperature. The combination of dried blood samples and high performance
      liquid chromatography provides an accurate system to screen for
      hemoglobinopathies, even after long periods of sample storage at ambient
      conditions.

PMID- 7507312
TI  - Preproinsulin messenger ribonucleic acid in the rat adrenal gland.
AB  - Many studies support the concept of insulin synthesis in tissues other than the
      pancreas. Our previous investigations have demonstrated the presence of insulin
      immunoreactivity in the adrenal medulla of the rat. This immunoreactivity was
      found to be associated with the chromaffin granule. This study is directed at
      isolating the messenger ribonucleic acid that encodes for preproinsulin. Reverse
      transcription coupled with polymerase chain reaction was used. Complementary
      deoxyribonucleic acid (cDNA) was amplified, extracted and reamplified. It was
      then subjected to digestion with four different restriction endonuclease enzymes.
      Its resemblance to the corresponding cDNA that encodes for preproinsulin I in the
      rat was established. Our results suggest that insulin is synthesized in the rat
      adrenal gland for autocrine, paracrine, neuromodulation or local physiologic
      function.

PMID- 7507313
TI  - [Characterization of renal cell carcinoma: current topics].
AB  - This article reviewed relatively new findings of renal cancer concerning
      epidemiology, molecular and cytogenic analysis for carcinogenesis, and
      immunological analysis. In recent years, increasing numbers of renal cancer have
      been found incidentally by ultrasonography or computerized tomography. These
      incidental tumors were detected at earlier stages and the prognosis was improved.
      The incidence of renal cancers detected incidentally by ultrasonic mass survey in
      a restricted area (incidental cancer) was 0.06%, which is much higher than the
      incidence of clinical renal cancers. Moreover, the incidence of renal cancers
      found in Japanese autopsy specimens (latent cancer) was 0.77%, which was
      extremely high. Moreover, the frequency of cancer multicentricity in kidneys
      removed for renal cancers was 0.07% by examining 100 kidneys. To investigate the
      biological characteristics of incidental and latent cancers including
      multicentric daughter tumors is a key point in determining the surgical
      indications. Specific oncogenes participating in the carcinogenesis of renal
      cancer have not been found so far, but c-myc oncogene was overexpressed in renal
      cancers. The deletion of 3 p chromosome was very often observed in renal cancers.
      The suppressor gene for carcinogens of renal cancer may be localized in 3p
      region. Renal cancer produced a transforming growth factor-alpha (TGF-alpha),
      which bound to epidermal growth factor receptor (EGFR) and upregulated the
      expression of EGFR and TGF-alpha. The autocrine loop of TGF-alpha and EGFR may
      stimulate the growth of renal cancer. Renal cancer patients had immunological
      reactions to autologous tumor cells in their sera, then renal tumors expressed
      class 1 (individually unique) antigens or class 2 (cancer shared) antigens.
      Immunological therapy may be useful for renal cancer. Finally, antiproliferative
      and antitumor effect of interferon alpha in renal cancer correlated reversely
      with the expression of F 33 antigen, which is expressed only in renal glomerulus
      and proximal tubule. We could discriminate the responder from the nonresponder
      for immunotherapy with interferon alpha. These findings could lead to the
      development of new modalities for renal cancer.

PMID- 7507315
TI  - Primary small cell carcinoma of the prostate: unusual modes of presentation.
AB  - Primary small cell carcinoma of the prostate is an uncommon condition. Between
      August 1989 and July 1991 seven patients with this pathology presented to the
      Repatriation General Hospital, Melbourne. Four of these patients presented by
      means not previously described. Included in this group is the first reported case
      of this tumour localized to the prostate gland and apparently cured by radical
      prostatectomy. The generally poor prognosis and lack of hormonal response
      associated with this condition warrant a greater awareness of the diagnosis among
      urologists.

PMID- 7507314
TI  - [CAMBO-VIP for advanced diffuse large cell lymphoma (LSG classification)--a long
      term follow-up study].
AB  - Twenty-two patients with advanced diffuse large cell lymphoma (LSG
      classification) were treated with the combination chemotherapy of
      cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin,
      vincristine, etoposide, ifosfamide and prednisolone (CAMBO-VIP) from Oct. 1987 to
      Sept. 1989. Eighteen (90%) of 20 evaluable patients achieved complete remission
      and 2 patients had partial remission. With a median follow-up of 52 mos, 3
      patients relapsed (17%), and 2 patients died. The actuarial overall survival and
      relapse-free survival at 4 years were estimated to be 90% and 83%, respectively.
      Myelosuppression was severe, but transient. No serious infection was seen, and no
      platelet transfusion was required. Oral mucositis and liver damage (Grade 3 in
      WHO grading) was seen in one patient each, but no treatment-related fatalities
      were observed. CAMBO-VIP is a well tolerated, effective treatment regimen for
      advanced diffuse large cell lymphoma.

PMID- 7507316
TI  - Immunosuppressants: tools to investigate the physiological role of cytokines.
AB  - The cyclic peptide Cyclosporine A (CsA) is best known as the immunosuppressive
      drug which has revolutionized organ transplantation. It selectively suppresses T
      cell activation by blocking the transcription of cytokine genes such as IL-2 at
      the level of transcription factor modulation. The structurally unrelated
      immunosuppressant FK 506 acts on the same pathway and blocks cytokine gene
      expression. In contrast, rapamycin, a structural analogue of FK 506, interferes
      with the immune response at a different level, by blocking the response induced
      by cytokines such as IL-2. Although these drugs have been most studied for their
      immunosuppressive activities, it is clear that their effects on cytokine pathways
      extend far beyond the sole IL-2-mediated responses involved in the immune
      response. For instance, CsA and FK 506 inhibit the transcription of IL-3, IL-4,
      IFN gamma, TNF alpha or GM-CSF by activated T cells, and rapamycin has been shown
      to block the response to various growth factors such as IL-3, IL-4 or IL-6. Here,
      we recap what is known about the effects of CsA, FK 506 and rapamycin on
      hematopoiesis in vitro and in vivo and extrapolate on what these drugs can teach
      us about the physiological role of cytokines for hematopoiesis.

PMID- 7507317
TI  - Human retinal pigmented epithelial cells produce nitric oxide in response to
      cytokines.
AB  - The present study demonstrates that human retinal pigmented epithelial cells
      produce nitric oxide (NO) upon co-treatment with interferon gamma (IFN gamma) and
      interleukin-1 beta (IL-1 beta). The biosynthesis of NO, which was measured by the
      accumulation of the stable end-product nitrite, requires an induction period of
      approximately 12 hours and continues for at least three days. The synthesis was
      abolished by the stereoselective inhibitors of NO synthase (NOS), NG-monomethyl-L
      arginine, N omega-nitro-L-arginine and N omega-nitro-L-arginine methyl ester and
      by cycloheximide. Transforming growth factor beta suppressed cytokine-induced
      NOS. The results indicate that cytokines such as IFN gamma and IL-1 beta are
      capable of inducing NOS, while TGF beta prevents this induction, in subcultured
      pigmented epithelial cells from the human retina.

PMID- 7507318
TI  - Comparison of substrate and inhibitor specificity of arginase and nitric oxide
      (NO) synthase for arginine analogues and related compounds in murine and rat
      macrophages.
AB  - Arginine utilizing enzymes in macrophages showed different specificities for
      various arginine analogues and derivatives as substrates and inhibitors. Isolated
      arginase was strongly inhibited by L-canavanine(Can) and L-ornithine(Orn) but
      only slightly by L-homoarginine(Hom) and L-argininamide(ArgNH2). These effects
      were not or only weakly observed when released urea was measured in long term
      cell cultures. On the other hand, both L-canavanine and L-argininamide were
      substrates for arginase in long-term cultures. The known inhibitors of NO
      synthase were ineffective. The mechanisms of inhibition were different for L
      canavanine and L-ornithine, but clear mechanisms could not be identified). NO
      synthase was studied only in long term cell cultures without purification.
      Certain N-guanidino (NG)-substituted arginine derivatives caused a marked
      inhibition while inhibitors of arginase had only slight or no effect. L
      homoarginine was also found to be the substrate of NO synthase. The comparison of
      these effects of arginine analogues and derivatives made possible a computer
      aided approximation for the fitting of active centers of these enzymes to their
      substrates.

PMID- 7507320
TI  - Insulin-like growth factor binding protein 3 (IGF-BP3) inhibits estrogen
      stimulated breast cancer cell proliferation.
AB  - We have recently demonstrated that exposure of MCF7 cells to antiestrogens in
      vitro results in both accumulation of IGF-BP3 in media and reduced mitogenic
      responsivity to IGFs (Cancer Res. 53:5193-5198). We show here that MCF7 cell
      proliferation in steroid-stripped, serum containing media is significantly
      attenuated by rhIGF-BP3 (p < 0.05), with a maximal 40% inhibition of serum
      stimulated growth achieved by 6.25nM IGF-BP3. 10(-10) M estradiol (E2)
      significantly stimulated MCF7 proliferation, and co-incubation of estrogen
      containing cultures with 50nM IGF-BP3 resulted in significant attenuation of the
      estrogen-stimulated proliferation ([3H]thymidine incorporation: E2, 147 +/- 18%
      of control; E2 +/- IGF-BP3, 111 +/- 18% of control, p < 0.05). These results
      demonstrate antagonism of steroid stimulated proliferation by an IGF binding
      protein and are compatible with the hypothesis that antiestrogen-induced
      accumulation of IGF-BP3 in the conditioned media of MCF7 cells contributes to the
      cytostatic action of these drugs.

PMID- 7507319
TI  - Laminar flow stimulates ATP- and shear stress-dependent nitric oxide production
      in cultured bovine endothelial cells.
AB  - Based on the fact that nitric oxide (NO) production is associated with changes in
      intracellular cGMP levels and is selectively inhibited by N omega-methyl L
      arginine (L-NME), we investigated the shear stress dependency of NO production in
      endothelial cells (ECs) from its cGMP responses to various shear stress loads.
      Cultured fetal bovine aortic ECs treated with a phosphodiesterase inhibitor,
      isobutylmethylxanthine (IBMX; 1 mM), were exposed to a laminar flow of Krebs
      buffer solution for 5 minutes in a parallel-plate flow chamber and examined for
      changes in intracellular cGMP levels by radioimmunoassay using an [125I] cGMP
      kit. Application of flow increased the cGMP levels. The increase was significant
      in the presence of extracellular ATP (1 microM)(control, 286.1 +/- 43.6; flow,
      506.5 +/- 44.9 fmol/10(7) cells; p < 0.001), but not in its absence (control,
      256.6 +/- 60.6; flow, 301.5 +/- 91.4 fmol/10(7) cells; N.S.). The cGMP levels
      increased significantly as the magnitude of shear stress applied increased.
      Treatment of ECs with a specific inhibitor of NO production, L-NMA (200 microM),
      completely inhibited the flow-induced increase in cGMP, and L-arginine reversed
      the L-NMA-induced inhibition, indicating that the increase in cGMP was due to NO
      produced by the flow. The flow-induced increase in NO production was markedly
      suppressed when extracellular Ca++ was chelated by adding EGTA to the perfusate.
      These findings suggest that flow stimulates NO production to increase cGMP levels
      shear stress-dependently in ECs and that extracellular Ca++ and ATP modulate the
      effects of flow.

PMID- 7507321
TI  - Cloning and expression of a human glucagon receptor.
AB  - A human glucagon receptor has been cloned from human liver tissue. The 1578-bp
      cDNA clone encodes a protein of 477 amino acids with 82% identity to the rat
      glucagon receptor. The predicted secondary structure and homology to known
      proteins places this receptor within the superfamily of seven transmembrane
      domain G protein coupled receptors. Transfection of the human glucagon receptor
      into COS-7 cells confers upon them high affinity binding for [125I] glucagon. In
      membranes prepared from COS-7 cells transfected with the human glucagon receptor,
      the binding of [125I] glucagon is inhibited with the rank order of potency
      glucagon > oxyntomodulin > glucagon-like peptide 1 (7-36) amide >> glucagon-like
      peptide 2 = gastric inhibitory peptide = secretin.

PMID- 7507324
TI  - Reaction to "Full inclusion": a reaffirmation of the right of students with
      learning disabilities to a continuum of services. Statement of the National Joint
      Committee on Learning Disabilities.

PMID- 7507322
TI  - Non-covalent interaction between poly(ADP-ribose) and cellular proteins: an
      application of a poly(ADP-ribose)-western blotting method to detect poly(ADP
      ribose) binding on protein-blotted filter.
AB  - We describe a sensitive method for the detection of interactions between poly(ADP
      ribose) and proteins. Proteins were blotted onto nitrocellulose filters and
      incubated with 32P-labeled poly(ADP-ribose). Purified core histones and poly(ADP
      ribose) polymerase were found to bind poly(ADP-ribose) polymer. Blots of HeLa
      cell protein extracts revealed a 48 kDa protein and several others of smaller
      than 35 kDa likewise bound the polymers even at high salt concentrations. Those
      proteins, along with a 69 kDa protein, also showed resistance to competitor DNA.
      Polymer binding of aforesaid HeLa extract proteins was restricted to polymers
      above 20 residues in length. Thus poly(ADP-ribose)-protein affinities were
      polymer-length dependent.

PMID- 7507323
TI  - Protein tyrosine phosphatase inhibition by angiotensin II in rat pheochromocytoma
      cells through type 2 receptor, AT2.
AB  - Two major isoforms of angiotensin II receptors, AT1 and AT2, have been defined on
      the basis of their ligand selectivity. While AT1 is known to mediate typical
      biological actions of angiotensin II as a cardiovascular regulator, the
      biological function of AT2 has not yet been established. In the present study
      using a rat pheochromocytoma cell line, which expresses AT2 exclusively, we found
      that angiotensin II inhibits phosphotyrosine phosphatase activity in vivo as
      measured by the inhibition of hydrolysis of [32P]-phosphate from the 32P-labeled
      synthetic peptide substrate, Raytide. This phosphotyrosine phosphatase inhibition
      was completely reversed by pertussis toxin, which indicates a G-protein coupled
      mechanism. In SDS-polyacrylamide gel electrophoresis we found that the
      phosphotyrosine group of an 85 kDa protein was a substrate mainly preserved,
      presumably as a consequence of the plausible intracellular phosphotyrosine
      phosphatase inhibition by angiotensin II.

PMID- 7507325
TI  - Serum concentrations of total sialic acid and sialoglycoproteins in relation to
      coronary heart disease risk markers.
AB  - This study investigated the relationship between serum sialic acid concentration
      and cardiovascular mortality. Correlations were determined between lifestyle
      related coronary heart disease risk markers (cigarette consumption, alcohol
      consumption, and leisure time physical activity), biological risk markers
      (apolipoprotein A1, apolipoprotein B, lipoprotein(a), and diastolic blood
      pressure) on the one hand and the concentration of sialic acid as well as sialic
      acid-rich acute phase proteins (orosomucoid, haptoglobin, and alpha 1
      antitrypsin) on the other. A total of 145 men aged 21-46 years and with a C
      reactive protein concentration below 5 mg/l were included. Total sialic acid
      concentration correlated significantly with apolipoprotein B (r = 0.48), number
      of cigarettes smoked daily (r = 0.32), and leisure time physical activity (r = 
      0.23) after adjustment for age and other cardiovascular risk markers. No
      significant partial correlations were found between serum total sialic acid
      concentration on the one hand and alcohol consumption, apolipoprotein A1,
      lipoprotein(a), and diastolic blood pressure on the other. Of the sialic acid
      rich glycoproteins, orosomucoid correlated with apolipoprotein B (r = 0.38),
      haptoglobin with cigarette consumption (r = 0.35) and leisure time physical
      activity (r = -0.26) and alpha 1-antitrypsin with cigarette consumption (r =
      0.18), leisure time physical activity (r = 0.17), alcohol consumption (r = 
      0.18), and apolipoprotein B (r = 0.21) after adjustment for age and other
      cardiovascular risk markers.

PMID- 7507326
TI  - Presence of growth-stimulating fibrin degradation products containing fragment E
      in human atherosclerotic plaques.
AB  - The key event in the formation of stenosing atherosclerotic lesions is widely
      thought to be smooth muscle cell proliferation, but the factors primarily
      responsible for initiating this remain uncertain. Previously we have shown that
      aqueous extracts of proliferative types of human atherosclerotic plaque stimulate
      cell proliferation in the chick chorioallantoic membrane (CAM). This has been
      attributed largely to the fibrin degradation products in the extracts, components
      removeable by affinity chromatography. We now demonstrate that the fibrinogen
      content of the extract, removeable by clotting out with thrombin, also makes a
      contribution to the activity by forming fibrin on the surface of the CAM.
      Affinity chromatography experiments using anti fragment D and E antisera indicate
      that activity resides in the E-containing fibrin fragments, consistent with
      previous work with FDP prepared in vitro.

PMID- 7507328
TI  - Induction, via immunization with a monoclonal antiidiotypic antibody, of viral
      envelope specific Ab3 antisera that neutralize retrovirus infectivity.
AB  - We have developed five mouse monoclonal antiidiotypic antibodies to the 35/56
      (Ab1) rat monoclonal that neutralizes retroviral infectivity by binding to the
      gp70f epitope of murine leukemia retrovirus. The anti-Id nature of these five
      Ab2s was evidenced by their inability to react with a panel of six other rat
      IgG2a kappa monoclonals isotype-matched to the 35/56 anti-gp70f mAb1, including
      two to the distinct epitopes "g" and "h" of gp70, or to normal rat IgG2a. On the
      basis of several competition assays four mAb2 were clearly either directed to the
      paratope of anti-gp70f mAb1 (.1C7, .1B, and .E) or not (.A, representing a
      noninternal image Ab2 alpha anti-Id). The P3E8 mAb2 was difficult to classify.
      Based on relative efficiency in these assays, .1C7 was chosen for further study,
      and upon injection was able to induce Ab3 responses in C57BL/6, BALB/c, and CBA
      mice. The fact that the Ab3 activity was detected in a competitive ELISA in which
      the hyperimmune antisera blocked the binding of Ab1 to Ab2, plus the ability to
      raise Ab3 neutralizing antibodies in three different mouse strains were
      consistent with .1C7 as an internal image Ab2 beta anti-Id. These results thus
      indicate the potential for internal-image monoclonal antiidiotypic antibody-based
      vaccines for retroviral diseases.

PMID- 7507327
TI  - Mononuclear leukocytes exposed to oxidized low density lipoprotein secrete a
      factor that stimulates endothelial cells to express adhesion molecules.
AB  - In animals fed a hypercholesterolemic diet, development of atherosclerosis is
      preceded by attachment of mononuclear leukocytes to the arterial endothelium.
      Early lesions begin to develop as monocytes migrate into the intima and ingest
      lipids. A major part of these lipids is believed to be derived from oxidatively
      modified low density lipoprotein (LDL). In the present study we demonstrate that
      human mononuclear leukocytes exposed to low concentrations of copper-oxidized LDL
      secrete one or several factors that stimulate the expression of intercellular
      adhesion molecule-1 (ICAM-1, CD54), vascular cell adhesion molecule (VCAM-1) and
      endothelial selectin (E-selectin-1, ELAM-1), whereas native LDL was found to be
      without effect. Exposure of endothelial cells to non-conditioned medium
      containing oxidized LDL did not influence the expression of adhesion molecules.
      Incubation of endothelial cells with conditioned medium from mononuclear cells
      grown in the presence of oxidized LDL also resulted in a three-fold increase in
      the binding of monocytoid U937 cells. The present findings suggest that
      mononuclear leukocytes exposed to oxidatively modified LDL in early
      atherosclerotic lesions may stimulate the recruitment of other leukocytes by
      secreting cytokines which induce the expression of adhesion molecules on the
      endothelium.

PMID- 7507331
TI  - Retrieval and amplification of DNA from unstained histopathological sections.
AB  - Testing of compounds for carcinogenic potential in vivo involves various
      experimental designs. A few of these techniques are directed to demonstrate the
      genotoxicity and mutagenicity of the compound by histopathology. These changes
      shown by histochemical means include monoclonal antibody directed cellular
      markers. Development of the polymerase chain reaction technique (PCR) for
      amplification of DNA has facilitated the investigation of molecular events
      related to the formation of malignant neoplasms. We describe here a method for
      screening tissues for mutations of the H-ras gene using monoclonal antibodies
      directed toward normal and mutant p21 proteins. Formalin-fixed, paraffin-embedded
      tissue sections are used to subsequently confirm the gene mutation by PCR
      amplification of the H-ras gene. The results indicated a successful application
      of this technique to demonstrate the presence of p21 oncoprotein in the tissues
      tested.

PMID- 7507329
TI  - Characterization of foot-and-mouth disease virus by monoclonal antibodies.
AB  - Monoclonal antibodies (MAbs) were produced against foot-and-mouth disease (FMD)
      virus types O1 Campos Br1/58, A24 Cruzeiro Br1/55, and C3 Indaial Br1/71, which
      are the strains used for production of FMD vaccines in the majority of South
      American countries. Within the library of MAbs produced, a group was selected on
      the basis of their neutralizing titer in cell culture, protective titer in
      suckling mice, sensitivity to trypsin, and specificity for virus structural
      proteins. The MAbs were utilized in an ELISA test format to compare European and
      South American representative field isolates with vaccine production strains in
      their r1 relationship as obtained by 50% complement fixation (CF50) with
      polyclonal antibodies (PAb) and their virus neutralization (VN) relationship
      obtained with sera from one-time-vaccinated and from revaccinated cattle,
      respectively. The MAbs selected varied in their reactivity against the different
      strains and, therefore, enabled us to compare field FMDV strains to those against
      which the MAbs were produced, with definite advantages over the r1 and VN ratios.
      Thus, panels of MAb produced with the vaccine strains and appropriately selected
      are significantly useful for the FMD-control programs because they serve to
      provide guidance on the immunological coverage provided by the vaccines against
      FMDV strains circulating in the field. The MAbs are also useful for the
      differentiation of FMD virus strains.

PMID- 7507330
TI  - Intranigral stimulation of oral movements by [Pro9] substance P, a neurokinin-1
      receptor agonist, is enhanced in chronically neuroleptic-treated rats.
AB  - Bilateral intranigral infusions of three different peptide agonists were made in
      rats exposed to fluphenazine decanoate, 30 mg/kg/month (FLU) or vehicle (CON) for
      seven months. Oral movements were monitored repeatedly during the neuroleptic
      pretreatment period, as well as before the intranigral infusion and during a 90
      min period postinfusion. The FLU group had an increased frequency of vacuous
      chewing movements (VCM) during the pretreatment period in comparison to controls.
      Intranigral infusion of the neurokinin-1 (NK1) receptor agonist, [Pro9]Substance
      P (2.5 nmol on each side), 5-7 weeks after the last FLU injection, caused a
      significant increase of VCM in both pretreatment groups, lasting 7 min after the
      infusion. The VCM response to [Pro9]Substance P in the FLU group was
      significantly higher than in the CON group. A NK2 agonist [Lys5, MeLeu9,
      Nle10]Neurokinin A(4-10) (2.5 nmol) failed to produce significant changes in oral
      activity. A Leu-enkephalin analogue [D-Ala2,D-Leu5]enkephalin (3.8 nmol) induced
      a massive biting behavior in both FLU and CON rats. Using VCM as a behavioral
      assay, an increased nigral sensitivity to a NK1 agonist is demonstrated in rats
      chronically exposed to neuroleptics. No corresponding alterations could be
      ascribed for the NK2 receptor agonist or the Leu-enkephalin analogue.

PMID- 7507332
TI  - Insulin-like growth factors, their receptors and binding proteins: increasing
      complexity.

PMID- 7507333
TI  - Error analysis of limb and orofacial praxis in children with developmental motor
      deficits.
AB  - Two models have been suggested to depict the relationship between disorders of
      limb and orofacial praxis. The first views apraxia as a unitary disorder in which
      the underlying mechanisms for each type are similar, while the second model
      suggests that there are two separate praxis systems: one for planning and
      controlling limb gestures and a second one for planning and controlling orofacial
      movements. The purpose of this study was to investigate whether a common
      mechanism may underlie deficits in limb and orofacial praxis in children. This
      was done by analyzing the types of praxis errors demonstrated by children with
      developmental motor deficits and normal controls when performing limb and
      orofacial gestures. Results indicated that there was consistency across
      modalities (i.e., limb, orofacial) in the types of praxis errors made by children
      with motor deficits, providing support for the idea that a common mechanism may
      underlie disruptions to limb and orofacial praxis in children. This study also
      examined developmental trends in gestural representation and in types of praxis
      errors. The findings revealed a striking developmental maturation in gestural
      ability between the ages of 6 and 11 years for all children. However, over this
      age range, children with developmental motor deficits were impaired relative to
      normal controls.

PMID- 7507334
TI  - From genotype to phenotype: computer-based modeling of gene expression with
      STELLA II.
AB  - STELLA II is a microcomputer program that is designed to simulate and animate the
      dynamics generated by biological systems in a quantitative fashion. The program
      employs the Macintosh user interface and includes a tool kit for assembling
      models, plus menus for setting parameters and selecting input or output.
      Quantitative relationships among components may be expressed with user-defined
      equations, graphical functions or data from spreadsheets. System dynamics are
      simulated by running the program after defining initial conditions, and results
      may be viewed immediately using windows for graphical or tabular plots. The
      present article describes how STELLA II may be used to simulate gene expression
      as an adjunct to experimentation or student-directed learning.

PMID- 7507335
TI  - A rise in postsynaptic Ca2+ potentiates miniature excitatory postsynaptic
      currents and AMPA responses in hippocampal neurons.
AB  - We have investigated the site of expression of the potentiation of excitatory
      postsynaptic currents (EPSCs) induced by the activation of postsynaptic voltage
      sensitive Ca2+ channels, by examining the effect of depolarizing pulses on
      miniature (m) EPSCs and responses to AMPA. Application of voltage pulses caused a
      approximately 2.5-fold increase in the mean amplitude of mEPSCs. This NMDA
      receptor-independent potentiation of mEPSC amplitudes was transient, returning to
      control values within 30-40 min. The potentiation was associated with a decrease
      in the number of small amplitude events and an increase in the number, as well as
      the maximum amplitude, of the larger events, with no apparent change in mEPSC
      kinetics. Accompanying the increase in mEPSC amplitudes, there was a 1.6-fold
      increase in the apparent frequency of events. Voltage pulse-induced potentiation
      was completely blocked by the inclusion of the Ca2+ chelator BAPTA in the
      recording pipette. Responses to repeated applications of AMPA were also
      potentiated following the application of voltage pulses, and the time course of
      this potentiation was similar to that observed with the mEPSCs. Our data indicate
      that rises in intracellular Ca2+ that occur independently of NMDA receptor
      activation can result in a potentiation of quantal size, which is due to an
      increase in the postsynaptic sensitivity of non-NMDA receptors.

PMID- 7507336
TI  - Tumor necrosis factors protect neurons against metabolic-excitotoxic insults and
      promote maintenance of calcium homeostasis.
AB  - Emerging data indicate that neurotrophic factors and cytokines utilize similar
      signal transduction mechanisms. Although neurotrophic factors can protect CNS
      neurons against a variety of insults, the role of cytokines in the injury
      response is unclear. We now report that TNF beta and TNF alpha (1-100 ng/ml) can
      protect cultured embryonic rat hippocampal, septal, and cortical neurons against
      glucose deprivation-induced injury and excitatory amino acid toxicity. The
      elevation of intracellular calcium concentration ([Ca2+]i) induced by glucose
      deprivation, glutamate, NMDA, or AMPA was attenuated in neurons pretreated with
      TNF beta. The mechanism whereby TNFs stabilize [Ca2+]i may involve regulation of
      the expression of proteins involved in maintaining [Ca2+]i homeostasis, since
      both TNF beta and TNF alpha caused a 4- to 8-fold increase in the number of
      neurons expressing the calcium-binding protein calbindin-D28k. These data suggest
      a neuroprotective role for TNFs in the brain's response to injury.

PMID- 7507337
TI  - Retinal ganglion cells express a cGMP-gated cation conductance activatable by
      nitric oxide donors.
AB  - We have identified a putative cGMP-gated cation conductance in rat retinal
      ganglion cells. Both in situ hybridization and polymerase chain reaction
      amplification detected transcripts in ganglion cells that were highly homologous
      to the cGMP-gated cation channel expressed in rod photoreceptors. Whole-cell
      patch-clamp recordings detected a current stimulated by cGMP due to activation of
      nonselective cation channels. This current had a reversal potential near 0 mV,
      showed some outward rectification, and could be blocked by Cd2+. The current
      could also be activated by a phosphodiesterase inhibitor and the nitric oxide
      donors sodium nitroprusside and S-nitrosocysteine. We propose that nitric oxide
      released from an identified subpopulation of amacrine cells may activate this
      channel to modulate ganglion cell activity.

PMID- 7507338
TI  - Neuronal acetylcholine receptors that bind alpha-bungarotoxin with high affinity
      function as ligand-gated ion channels.
AB  - Neuronal membrane components that bind alpha-bungarotoxin with high affinity can
      increase intracellular levels of free calcium, demonstrating the components
      function as nicotinic receptors. Though such receptors often contain the alpha 7
      gene product, which by itself can produce ionotropic receptors in Xenopus
      oocytes, numerous attempts have failed to demonstrate an ion channel function for
      the native receptors on neurons. Using rapid application of agonist, we show here
      that the native receptors are ligand-gated ion channels which are cation
      selective, prefer nicotine over acetylcholine, and rapidly desensitize. Much of
      the calcium increase caused in neurons by the receptors under physiological
      conditions appears to result from their depolarizing the membrane sufficiently to
      trigger calcium influx through voltage-gated channels.

PMID- 7507339
TI  - Prolyl isomerase requirement for the expression of functional homo-oligomeric
      ligand-gated ion channels.
AB  - Ligand-gated ion channel subunits show a striking abundance of highly conserved
      proline residues. We, therefore, tested the hypothesis that peptidyl-prolyl
      isomerases may be involved in the maturation of these channels. Cyclosporin A, a
      selective blocker of a ubiquitous isomerase cyclophilin, reduced the surface
      expression in Xenopus oocytes of functional homo-oligomeric receptors containing
      nicotinic acetylcholine receptor subunit alpha 7 without blocking alpha 7
      polypeptide synthesis. This effect could be generalized to the homo-oligomeric 5
      hydroxytryptamine type 3 receptor but not to the hetero-oligomeric muscle
      nicotinic receptor. An alpha 7 receptor could be rescued from cyclosporin A
      blockade by coexpressed muscle non-alpha subunits. The effect of cyclosporin A
      was reversed by overexpression of exogenous rat brain cyclophilin. These findings
      indicate that cyclophilins may play a critical role in the maturation of homo
      oligomeric receptors, acting directly or indirectly as prolyl isomerases or as
      molecular chaperones.

PMID- 7507340
TI  - Retrograde axonal transport of LIF is increased by peripheral nerve injury:
      correlation with increased LIF expression in distal nerve.
AB  - Leukemia inhibitory factor (LIF) is a cytokine that affects the survival and
      differentiation of certain neuronal populations in vitro. To identify LIF
      responsive neurons in the adult rat, we have demonstrated retrograde axonal
      transport of 125I-LIF to sensory and motor neurons. The accumulation of 125I-LIF
      by both cell types was significantly increased by prior sciatic nerve crush.
      Retrograde transport of 125I-LIF was inhibited by excess unlabeled LIF but not by
      related cytokines, indicating a specific receptor-mediated mechanism. Northern
      blot analysis revealed LIF expression in peripheral nerve that was increased in
      distal segments after axotomy. The correlation between LIF expression and
      increased retrograde transport following injury suggests that LIF plays a role in
      peripheral nerve regeneration.

PMID- 7507341
TI  - Multivesicular release from excitatory synapses of cultured hippocampal neurons.
AB  - Release of neurotransmitter from presynaptic terminals occurs by exocytosis of
      vesicular contents into the synaptic cleft. We find that more than one quantum of
      transmitter can interact with the same population of postsynaptic NMDA receptors
      in conditions which increase the probability of transmitter release. Increasing
      release probability also results in proportional increases in both AMPA and NMDA
      receptor components of the synaptic current. These results suggest that the
      fraction of AMPA and NMDA receptors occupied by transmitter following the release
      of a single quantum is similar. Based on AMPA and NMDA receptor responses of
      outside-out patches to short applications of glutamate, we suggest that both
      receptor types may be saturated normally by synaptic release.

PMID- 7507342
TI  - CFTR expression and chloride secretion in polarized immortal human bronchial
      epithelial cells.
AB  - A major limitation in the study of vectorial ion transport, secretion, and
      differentiated function in the human airway epithelium has been the lack of
      suitable cell culture systems. Progress in this direction has been made through
      the transformation of primary cultured epithelial cells. However, these
      transformants tend to lose differentiated properties with increasing serial
      passage, particularly following crisis. The successful establishment of a
      postcrisis SV40 large T-antigen transformed epithelial cell line derived from
      human bronchial epithelium is described. This cell line, 16HBE14o-, retains
      differentiated epithelial morphology and functions. Cell cultures show the
      presence of tight junctions and cilia, and monolayers generate transepithelial
      resistance, as measured in Ussing chambers, and retain beta-adrenergic
      stimulation of cAMP-dependent chloride ion transport, measured either by 36Cl-
      efflux or as short-circuit current in Ussing chambers. The cells also increase
      chloride transport in response to bradykinin or calcium ionophore. In addition,
      16HBE14o- cells express levels of both the cystic fibrosis transmembrane
      conductance regulator (CFTR) mRNA and protein readily detectable by Northern and
      Western hybridization analysis, respectively. These cells provide a valuable
      resource for studying the modulation of CFTR and its role in regulation of
      chloride ion transport in human airway epithelium as well as other aspects of
      human airway cell biology.

PMID- 7507344
TI  - Production of granulocyte colony-stimulating factor by head and neck carcinomas.
AB  - Detectable levels of G-CSF by enzyme-linked immunosorbent assay (ELISA) were
      found in sera of 4 out of 15 patients with head and neck carcinomas. Also cells
      prepared from the tumors of these 4 patients secreted G-CSF. The supernatants of
      cells derived from all 15 patients did not contain granulocyte-monocyte CSF,
      monocyte CSF, tumor necrosis factor-alpha, transforming growth factor-beta 1,
      epidermal growth factor, interleukin (IL)-1 beta and IL-6. These findings suggest
      that leukocytosis in patients with carcinomas might be due to the production of G
      CSF by tumor cells.

PMID- 7507346
TI  - A tumor cell line producing granulocyte colony-stimulating factor and an immune
      suppressive factor.
AB  - From a patient, both a cell line incapable of secreting granulocyte colony
      stimulating factor (G-CSF) (TC873) and a cell line capable of secreting G-CSF
      (TCM902) were established. The effector cells induced, with TC873 cells showed a
      high lytic capacity against two types of tumor cells. The effector cells induced
      by TCM902 cells did not show such capacity. Furthermore, the TCM902 cells
      excreted a factor suppressing the proliferation of lymphokine activated killer
      (LAK) cells and the autologous tumor cell lysis of tumor associated lymphocytes.
      This factor probably is TFG-beta 1.

PMID- 7507345
TI  - The detection of a breast cancer antigen on MCF-7 cells reactive with the TCR
      (alpha) of a specific killer T cell line.
AB  - We established several immortalized human T cell lines by cotransfecting primary
      lymphocytes derived from breast cancer patients with human c-myc and human c-Ha
      ras oncogenes. A CD8 positive (CD8+) killer T cell line, FT-8, exhibited in vitro
      specific cytotoxicity to a human breast cancer cell line, MCF-7. The FT-8 cells
      suppressed the growth of MCF-7 cells transplanted to athymic mice. The cytotoxic
      reaction was caused via T cell antigen receptor (TCR) on MCF-7 cells, because
      monoclonal antibodies against the TCR inhibited the cytotoxicity of FT-8 cells.
      The TCR (alpha) cDNA of FT-8 was cloned by using a PCR amplification technique
      and expressed by a cell-free in vitro translation system. The TCR (alpha) protein
      recognized a target antigen of 32 KDa on MCF-7 cells.

PMID- 7507343
TI  - [Colonic obstruction in Whipple's disease].
AB  - A patient with Whipple's disease presented with low intestinal obstruction and
      hemorrhage due to mesenteric retraction which was attributed to intra-abdominal
      enlarged lymph nodes. Ultrastructural findings included abundant intracellular
      bacilli. This complication of Whipple's disease has not been previously described
      and should be listed in the differential diagnosis of colonic obstruction.

PMID- 7507347
TI  - One step beyond PSA.

PMID- 7507348
TI  - Quality of life dimensions that are most important to cancer patients.
AB  - Despite the introduction of quality of life measurements into clinical trials
      during the past several years, there is uncertainty about how to translate
      quality of life information from the research setting to meaningful practice
      decisions. In part, this is due to the fact that physicians do not speak the same
      language as behavioral scientists and are not as comfortable in exploring social
      and emotional functioning as they are in inquiring about symptoms and other
      physical concerns. Until more information is available about which quality of
      life dimensions are of greatest concern to different patient cohorts and until
      reliable tools evolve to evaluate individual patient quality of life needs, it is
      likely that most physicians will rely on the unstructured patient interview to
      obtain quality of life information. As more is learned about the value patients
      place on specific quality of life dimensions, it will allow physicians to better
      address patients' symptoms, physical function, and psychosocial health concerns.

PMID- 7507349
TI  - Developmental regulation of acidic fibroblast growth factor (aFGF) expression in
      bovine retina.
AB  - Acidic fibroblast growth factor (aFGF) is a signalling molecule implicated in a
      wide variety of biological processes such as cell growth, differentiation and
      survival. It has been purified from bovine retina. The present study was carried
      out to detect which cells in the bovine retina expressed aFGF at the different
      stages of embryonic and post-natal development. The specific aFGF mRNA and
      protein were detected by in situ hybridization employing riboprobes and
      immunocytochemistry using affinity purified polyclonal human recombinant aFGF
      antibodies respectively. No signal was detected by either technique until 4-5
      months and then there was progressive expression of aFGF with terminal
      morphogenesis of the retina. By 8-9 months of embryonic development, nuclei of
      the 3 neuronal layers (ganglion cell layer, inner and outer nuclear layers) were
      all uniformly and intensely labeled. A slight labeling of the pigmented
      epithelium of the retina was also visible throughout development and maturation.
      These results showed a good correlation between message and protein expression in
      these cell types. In contrast, glial cells in the nerve fiber layer and vascular
      endothelial cells displayed a nuclear immunostaining for the protein in the
      absence of message. These data suggest that aFGF plays a role in the late steps
      of retinal differentiation by autocrine and paracrine mechanisms.

PMID- 7507350
TI  - Expression of the HNK-1 epitope is unaltered among early chick epiblast cells
      despite behavioral transformation by inducing factors in vitro.
AB  - Dissociated epiblast cells from pre-streak chick blastoderms have been exposed,
      in short-term culture on a fibronectin (FN) substratum, to recombinant mammalian
      activin and to mammalian basic fibroblast growth factor (bFGF). Such cultures
      have also been made on this substratum pre-conditioned by culture of a
      transfected cell line expressing the mammalian Wnt-1 gene. The former two factors
      induce changes of FN adhesiveness and other behavior, such that the cultures
      after 6 h resemble cultures newly set up from the young primitive streak or
      substreak hypoblast region of similarly aged blastoderms that have developed
      onward across the intervening period (see Cooke and Wong, Development 111: 197
      212, 1991 for related results). Over 95% of cells are potentially responsive, and
      with relatively high concentration of activin there is also production of nodular
      structures due to strong cell-cell adhesion, as in cultures from Hensen's node or
      the anterior streak. Pre-conditioning of the substratum by transfected Wnt-1
      expressing cells does not appear specifically to alter behavior in such epiblast
      cultures, though these experimental cells, and not control-transfected ones,
      produce striking alterations of chick development in other experiments (Cooke et
      al., in preparation). Up to 20% of cells in control cultures from central or
      'marginal zone' pre-streak epiblast express the HNK-1 epitope, while up to 60% of
      cultured early streak cells cleaned of hypoblast do so.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7507351
TI  - Production of alpha-fetoprotein by human submandibular gland.
AB  - Alpha-fetoprotein (AFP) is a 590 amino acid polypeptide that was initially
      defined as an embryonal serum globulin. The yolk sac endoderm, fetal liver and
      fetal gut were shown to be the main sites of AFP synthesis in the embryo (Gitlin
      and Boesman, J. Clin. Invest. 46: 1010-1016, 1967). AFP synthesis is still
      continued in human adults (Ruoslahti and Seppala, Int. J. Cancer 8: 374-383,
      1971) although the physiological level of serum AFP is lower than 10 ng/ml. AFP
      was also demonstrated in certain tumors and in various diseases or conditions
      such as yolk sac tumor, hepatoma, hepatoblastoma, acute and chronic liver
      cirrhosis, pregnancy and so on (Abelev, Adv. Cancer Res. 14: 295-358, 1971;
      Ruoslahti and Seppala, Cancer Res. 29: 275-346, 1979). Salivary glands have not
      been implicated in AFP synthesis. We investigated the expression of AFP in normal
      human salivary glands by immunohistochemistry with a monoclonal antibody against
      AFP, and documented immunoreactivity in intercalated and striated ducts of adult
      human submandibular glands.

PMID- 7507353
TI  - Peptide-containing neurons remain unaffected after intestinal
      autotransplantation: an experimental study in the piglet.
AB  - The gut is richly supplied with peptide-containing nervous elements. In the
      present immunocytochemical study the origin, occurrence and topographical
      distribution of nerves containing vasoactive intestinal polypeptide (VIP),
      enkephalin, substance P (SP), somatostatin, neuropeptide Y (NPY), calcitonin gene
      related peptide (CGRP), gastrin-releasing peptide (GRP) and galanin were
      investigated in the porcine small intestine. In order to study the origin
      (extrinsic or intrinsic) of the nerve fibers, specimens from autotransplanted and
      extrinsically denervated jejunum were examined. Furthermore, possible changes in
      the distribution of intrinsic neurons after extrinsic denervation were studied.
      In the control jejunum each nerve fiber population had its own characteristic
      topographic distribution. There was no overt difference in distribution pattern
      of peptide-containing nerve fibers and cell bodies between the transplanted and
      the control segment except that NPY-, SP- and CGRP-containing nerve fibers
      disappeared around blood vessels. Thus VIP-, somatostatin-, GRP-, enkephalin- and
      galanin-containing nerve fibers were visibly unchanged in the transplanted
      segment. The results support the view that the peptide-containing nerve fibers
      are mainly intrinsic in origin except the NPY-, SP- or CGRP-containing
      perivascular nerve fibers which are extrinsic to the gut wall. In addition, the
      results of the present study suggest that transplantation and extrinsic
      denervation have no major effect on the distribution pattern of the intrinsic
      neuronal systems.

PMID- 7507355
TI  - A method for determining the activity state of hair follicles.
AB  - A histological method is described for determining the proportion of growing hair
      follicles in skin samples. A variation of the Sacpic staining method, modified
      for bulk processing, produces high contrast staining of the principal tissue
      types present in skin. In particular, the inner root sheath is accentuated,
      facilitating detection of active follicles. Skin preparations from a range of
      species are used to illustrate structural characteristics of follicles viewed in
      cross section at various stages of the hair cycle and to establish criteria for
      classification of the state of activity of follicles. The hair cycle may be
      divided into quiescent and active states at the points of rapid transition (early
      pronanagen and mid catagen). Data from repeated skin biopsies from ferrets and
      goats are also used to demonstrate quantitative estimation of follicle activity,
      change in compound follicle size, and the relationship between follicle type and
      fiber medullation.

PMID- 7507354
TI  - Post-traumatic pancreatic pseudocyst: non-operative conservative management-
      report on 3 cases.
AB  - The authors report on 3 cases of post-traumatic pancreatic pseudocysts in
      children. Complete healing occurred with non-operative conservative treatment and
      total parenteral nutrition. Daily follow-up with clinical evaluation, abdominal
      ultrasound and lab exams are detailed under definite criteria of selection and
      follow-up. This mode of treatment might be considered as an alternative to
      exploratory laparotomy and external drainage.

PMID- 7507356
TI  - Histochemical heterogeneity of mast cells in rat dermis.
AB  - The dermal mast cells of Wistar rats were studied following fixation in either
      10% phosphate buffered formalin or Carnoy's solution and staining with either
      toluidine blue or alcian blue:safranin O. Granules of mast cells appeared
      heterogeneous following fixation with formalin and staining with alcian
      blue:safranin O, but not when stained with toluidine blue. The number of mast
      cells observed in skin fixed in Carnoy's solution was greater than the number
      observed in equivalent samples of skin fixed in formalin (p < 0.01) when both
      samples were stained with toluidine blue. In formalin fixed skin stained with
      alcian blue:safranin O, there were three populations of mast cells designated as
      "blue," "red" or "mixed." "Blue" mast cells, containing only alcian blue stained
      granules, "red" mast cells, containing only safranin O stained granules, and
      "mixed" mast cells, containing both alcian blue and safranin O stained granules
      accounted for 77.6 +/- 3.0, 6.6 +/- 2.5 and 15.8 +/- 2.5% of the total mast cell
      population, respectively. In skin specimens fixed in Carnoy's solution and
      stained with alcian blue:safranin O the mast cells contained only blue granules
      (alcian blue positive). The number of mast cells observed in Carnoy's fixed skin
      sections was less than the number seen in formalin fixed skin sections when both
      were stained with alcian blue/safranin O. This indicates that there is a group of
      mast cells which do not stain with safranin O after fixation with Carnoy's
      solution.

PMID- 7507357
TI  - Evaluation of DAPI as a fluorescent probe for DNA in viable Petunia protoplasts.
AB  - 4',6-Diamidino-2-phenyl-indole (DAPI), is a fluorescent probe that specifically
      and quantitatively stains DNA. Electroporation of viable Petunia protoplasts in
      the presence of DAPI revealed integral fluorescence that was similar for both the
      electroporated and fixed protoplasts, indicating quantitative staining of DNA.
      DAPI fluorescence was localized in the nuclei of viable protoplasts of Petunia.
      Protoplasts had a short term viability of 56-65% of the control (non
      electroporated, unstained) protoplasts as determined by fluorescein diacetate
      staining 24 hr following electroporation in the presence of DAPI. The majority
      (84% of the number originally cultured) of these protoplasts subjected to
      electroporation were able to form a cell wall, but most did not form microcalli
      because they were blocked in cell division. The three week plating efficiency for
      protoplasts exposed to DAPI was 4% of the original number of protoplasts
      initially cultured compared to 30% for the control. DAPI should not be used as a
      fluorescent probe for plant protoplasts when the protoplasts are cultured for
      sustained growth because the levels of DAPI required to obtain quantitative
      staining of the DNA resulted in inhibition of the cell cycle. DAPI may, however,
      be used as a fluorescent DNA probe for short term (24 hr) studies.

PMID- 7507352
TI  - Transgenic mice in the study of cytokine function.

PMID- 7507358
TI  - Rapid screening of low molecular mass proteinuria: evaluation of the first
      immunochemical test strip for the detection of alpha 1-microglobulin in urine.
AB  - A new semiquantitative immunochemical test strip for urinary alpha 1
      microglobulin, a marker protein for tubular proteinuria, was assessed. This test
      strip has four colour zones, reflecting alpha 1-microglobulin concentrations of
      ca. 10, 25, 50, and 80 mg/l. alpha 1-Microglobulin concentrations were measured
      by means of the test strip and an immunonephelometric method in 330 samples
      collected as the second voided morning urine. The reading time of the test strip
      must be strictly observed. Reading one minute earlier or later than the 5 min
      stated in the instructions led to misclassification of over 70% of the results.
      Correlation between both methods was highly significant, with a Spearman rank
      correlation coefficient of rs = 0.84 (P < 0.001). There was a partial overlap of
      the test strip results in different concentration ranges. An elevation of alpha 1
      microglobulin was defined as > 25 mg/l, calculated as the upper limit of the
      central 95% interval of alpha 1-microglobulin concentration in urine samples
      measured in a previous study of 304 healthy adults. Using this definition of
      alpha 1-microglobulin elevation, a sensitivity of 97.5%, specificity of 73.6%, a
      false-positive rate of 16.6%, and a false-negative rate of 0.9% of the test strip
      results were obtained. A fraction of 82.4% of the 330 samples investigated was
      correctly classified as having increased alpha 1-microglobulin concentration or
      not. Methodical improvements of the test strip are necessary to reduce
      overlapping results, in order to make the test suitable for screening purposes.

PMID- 7507359
TI  - Comparison of cytokeratin fragment 19 (CYFRA 21-1), tissue polypeptide antigen
      (TPA) and tissue polypeptide specific antigen (TPS) as tumour markers in lung
      cancer.
AB  - Recently CYFRA 21-1, a new tumour marker measuring a fragment of cytokeratin 19,
      was introduced and proved to be suitable for the follow-up care and monitoring of
      the therapy of non-small cell lung carcinomas, especially squamous cell
      carcinomas of the lung. Besides CYFRA 21-1, there are two other tumour markers
      available, called tissue polypeptide antigen (TPA) and tissue polypeptide
      specific antigen (TPS), which also measure different cytokeratins in serum. In a
      retrospective study we investigated the clinical significance of these 3
      cytokeratin markers in lung cancer compared with carcinoembryonic antigen (CEA),
      squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). We
      investigated the sera of 50 healthy persons, 273 patients with various benign
      diseases and 218 patients with histologically proven lung cancer. In a first step
      the specificity versus benign diseases of the lung was established for all the
      markers, and was fixed at 95%. Then the single and combined sensitivities were
      calculated. CYFRA 21-1 proved to possess the highest sensitivity in lung cancer
      in general (61%), in non-small cell lung carcinomas (64%), in squamous cell
      carcinomas (79%), in adenocarcinomas (54%) and in large cell carcinomas (65%). In
      small cell lung carcinomas, neuron-specific enolase proved again to be the marker
      of first choice (55%). Combined determinations proved clearly increased
      sensitivity only for large cell carcinomas (CYFRA 21-1 + TPA: 77%) and for small
      cell lung carcinomas (CYFRA 21-1 + NSE: 62%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507360
TI  - Not less likely than before that mean CSF HVA may be high in autism.

PMID- 7507361
TI  - Contact activation in human plasma is triggered by zinc ion modulation of factor
      XII (Hageman factor).
AB  - Conditions for triggering factor XII to function in the autoactivation reaction
      in blood coagulation in the presence of different surfaces have been studied
      using prekallikrein-deficient plasma. Autoactivation was recorded in a
      chromogenic assay by measuring the amidolytic activity of factor XIIa. The
      results showed that autoactivation of factor XII was achieved only after
      modulation of factor XII. This modulation was mediated by Zn2+ and did not
      require an activating surface. Following modulation, the autoactivation proceeded
      in the presence of a negatively charged phospholipid or sulphatide, but the
      sulphatide-mediated autoactivation was inhibited by Zn2+. In the presence of Zn2+
      (6.6 mumol/ml plasma), the rate constant for the autoactivation following
      modulation was calculated to be 3.1 x 10(4) M-1 s-1 and 1.2 x 10(4) M-1 s-1 for
      the phospholipid and the sulphatide-mediated reactions, respectively. In the
      absence of Zn2+ no activation was observed in the presence of a negatively
      charged phospholipid. After removal of Zn2+ by EDTA, the rate constant for the
      sulphatide-mediated autoactivation increased to 5.7 x 10(4) M-1 s-1 in the
      presence and 1.0 x 10(5) M-1 s-1 in the absence of a negatively charged
      phospholipid (phosphatidylinositol phosphate). Dextran sulphate was not able to
      mediate autoactivation, in either the presence or absence of Zn2+. Aprotinin
      completely blocked the modulation and/or autoactivation. Soy bean trypsin
      inhibitor prolonged the period required for autoactivation to start, but had no
      effect on the autoactivation rate. The main conclusions are that Zn2+ is required
      to initiate contact activation, modulating factor XII for autoactivation. This
      modulation does not require the presence of an activating surface.

PMID- 7507362
TI  - Alterations of haemostatic markers in various subtypes and phases of stroke.
AB  - The purpose of this study was to clarify differences in coagulation and
      fibrinolytic activation between the various subtypes and phases of ischaemic
      stroke. Haemostatic activation markers were measured in 52 patients with
      cardioembolic stroke, 32 with atherothrombotic stroke and 54 with lacunar stroke
      and compared with 23 age-matched controls. Data were obtained in the acute (< or
      = 7 days after onset), subacute (8-28 days) and chronic (> or = 29 days) phases
      of stroke. In patients with cardioembolic stroke, D-dimer and alpha 2-antiplasmin
      plasmin complex levels were higher during the acute and subacute phases, while
      thrombin-antithrombin III complex levels were higher during the acute phase than
      in patients with lacunar stroke and controls. In cardioembolic stroke,
      fibrinopeptide A was increased during the acute and subacute phases, thrombin
      antithrombin III complexes were higher during the subacute phase and D-dimer
      levels were higher during the chronic phase. Protein C activity was lower during
      the acute phase than in atherothrombotic stroke, lacunar stroke and controls.
      Protein C antigen was lower during the acute phase than in lacunar stroke and
      controls and during the chronic phase than in lacunar stroke. In contrast, only D
      dimer levels were higher in atherothrombotic stroke patients than controls during
      the acute and chronic phases and no significant alterations in these markers were
      observed in the patients with lacunar stroke. These findings suggest that
      measurement of molecular markers of coagulation and fibrinolysis may be useful
      for detecting intracardiac thrombin and plasmin generation in patients with
      cardioembolic stroke.

PMID- 7507363
TI  - Effects of direct percutaneous transluminal coronary angioplasty treatment of
      acute myocardial infarction on plasma levels of haemostatic and fibrinolytic
      factors.
AB  - Although thrombolytic therapy is used widely for treatment of acute myocardial
      infarction (AMI), thrombolysis itself increases thrombin activity and may cause
      reocclusion of infarct-related vessels. Direct percutaneous transluminal coronary
      angioplasty (PTCA) is an effective treatment for AMI; however, it is not clear
      what effects PTCA has on coagulation and fibrinolysis. We investigated
      coagulation and fibrinolytic factor concentrations before and after direct PTCA.
      Plasma levels of thrombin-antithrombin III complex (TAT), D-dimer, plasmin-(alpha
      2-antiplasmin complex (PAP), tissue-type plasminogen activator (t-PA) antigen and
      plasminogen activator inhibitor (PAI)-1 antigen were followed in twelve patients
      treated with direct PTCA for AMI. Before PTCA, only TAT concentrations were
      significantly elevated compared to normal controls. D-dimer, TAT, PAP and PAI-1
      concentrations were similar before and after PTCA. Eleven patients had no
      recurrent ischaemia and no restenosis on follow-up coronary angiography. These
      data confirm that direct PTCA is less likely than thrombolysis to affect
      coagulation and fibrinolysis.

PMID- 7507364
TI  - Simultaneous synthesis of peptide libraries on single resin and continuous
      cellulose membrane supports: examples for the identification of protein, metal
      and DNA binding peptide mixtures.
AB  - Peptide libraries were simultaneously synthesized on single supports by double
      coupling 0.8 equivalents of an equimolar acylating amino acid mixture consisting
      of 19 amino acids (cysteine omitted) at randomized sites, thus compensating for
      the different coupling rates of the amino acids. Peptide epitope mixtures, as
      well as very complex mixtures such as a completely randomized hexapeptide, were
      prepared and analyzed by HPLC and amino acid analysis. The results obtained
      indicate that this method can be applied to the synthesis of peptide libraries.
      Parts of a simultaneously synthesized solution phase combinatorial library
      XXB1B2XX were successfully used for the detection of the linear epitope HFND of
      transforming growth factor-alpha (TGF alpha) recognized by the monoclonal
      antibody Tab2. Furthermore, novel combinatorial peptide libraries XXB1B2XX were
      prepared on continuous cellulose membrane supports, also allowing the
      identification of TGF alpha epitope sequences. In addition, peptide mixtures that
      bound to a double-stranded DNA (15mer) and silver were identified. These
      preliminary results indicate that cellulose-bound combinatorial peptide libraries
      can be used for the rapid and inexpensive screening of millions of peptides to
      identify single molecules that bind any given ligand such as proteins, nucleic
      acids and metals.

PMID- 7507365
TI  - A giant tumor of the mesocolon found to be metastasis from an alpha-fetoprotein
      producing gastric carcinoma: report of a case.
AB  - We present herein an extremely rare case of metastasis from a gastric carcinoma
      to the mesocolon. A 71-year-old woman underwent a laparotomy for gastric cancer
      with an intra-abdominal mass. Her serum alpha-fetoprotein level was very high at
      3,560 ng/ml. The abdominal mass was subsequently revealed to be a metastatic
      tumor of the transverse mesocolon derived from an alpha-fetoprotein-producing
      gastric carcinoma, but no other metastatic focus was found. An
      immunohistochemical study revealed alpha-fetoprotein-positive cells in both
      lesions. The serum alpha-fetoprotein level became normal after the operation
      which was followed by a course of chemotherapy, and no recurrence has been
      observed thus far in 6 months of follow up.

PMID- 7507366
TI  - Expression and function of the CD44 glycoprotein in melanoma cell lines.
AB  - We have analysed a panel of murine and human melanoma cell lines for expression
      of the glycoprotein CD44. All 12 cell lines examined expressed CD44 at their cell
      surfaces, as demonstrated by fluorocytometric analysis using monoclonal
      antibodies (MAbs) IM7 and F10.44.2. Northern analysis revealed three transcript
      sizes that were 4.5, 2.2, and 1.5 kb in the human cell lines and 4.5, 3.0, and
      1.5 kb in the murine cell lines. Levels of mRNA did not correlate with level of
      surface expression, which was highly variable between the cell lines. RT-PCR
      analysis of mRNA revealed that the major band identified was the expected 792 bp
      fragment indicative of the CD44H haemopoietic form, compared to a 1194 bp form
      found in the human colorectal adenocarcinoma cell line HT29, indicative of the
      CD44E epithelial form. There was no evidence of variant CD44 mRNA in our panel of
      melanomas. Functional assays revealed no clear correlation between the level of
      cell surface CD44 and the ability of the melanoma cell lines to adhere to
      hyaluronate. Rather adherence appeared to relate to the activation status of CD44
      on the different cell lines as a consequence of MAb stimulation (e.g. the 1735P
      line demonstrated a 46.2 +/- 5.7% adherence in an inactivated state versus 62.4
      +/- 5.6% adherence in an activated state to 5 mg/ml hyaluronate) and suggests
      that the functional capacity of CD44 expressed by melanoma cells may be modified
      more by activation state than by RNA splicing.

PMID- 7507367
TI  - Growth in methylcellulose of human mast cells in hematopoietic colonies
      stimulated by steel factor, a c-kit ligand.
AB  - We examined the effect of Steel factor (SLF) on the development of human mast
      cells in hematopoietic colonies from cord blood mononuclear cells in
      methylcellulose culture. When cord blood cells were cultured for 3 weeks, SLF
      increased the cellular tryptase levels detected in total cultured cells. It also
      stimulated the formation of small-cell colonies consisting mainly of
      polymorphonuclear granulocytes and immature blastoid cells in a concentration
      dependent manner but not the formation of colonies consisting of large
      macrophagic cells. A low percentage of tryptase-positive mast-cell-like cells was
      found in 39 out of 100 granulocyte/blastoid cell colonies. Four of the 100
      colonies contained 10-20% tryptase-positive cells, but we failed to observe
      colonies consisting of > 20% of tryptase-positive cells. These results suggest
      that the effect of SLF on mast cell growth is brought on by stimulating the
      growth of primitive hematopoietic progenitors.

PMID- 7507368
TI  - Pharmacological evaluation of the inhibitory effect of extracts from Anchietia
      salutaris on the histamine release induced in the rat and the guinea pig.
AB  - The tea made with leaves and stems of plant Anchietia salutaris is traditionally
      used in Brazil to treat allergies. We examined the effects of a crude aqueous
      extract and of purified fractions of this plant on the histamine release induced
      in rat and guinea pig tissues. The crude extract (3-10 micrograms/ml) inhibits
      the histamine release induced by compound 48/80 (0.5 microgram/ml) and antigen in
      rat peritoneal mast cells. The inhibition is significant after 10 s of
      preincubation and is completed after 3 min. The crude extract dissolved in the
      perfusion fluid (1-30 micrograms/ml) also inhibits the histamine release induced
      in guinea pig heart by cardiac anaphylaxis and in hearts from pretreated animals
      (10-100 mg/kg i.p.). In pretreated animals, the effect manifests after 3 h, is
      maximum after 12 h and disappears after 48 h. The histamine release induced in
      isolated guinea pig heart by ionophore A23187 is inhibited by similar doses as in
      antigen-induced histamine release. Extraction with solvents concentrated the
      active principle(s) in the hexane fractions, as demonstrated by the inhibition of
      the histamine release induced by antigen in isolated cells from guinea pig heart
      dispersed with collagenase. In subfractions produced by the fractionation of the
      hexane fraction, the active principle(s) concentrated in the subfractions
      obtained by extraction with hexane and ethyl acetate, which shows the low
      polarity of the compound(s). The same subfractions that inhibit the histamine
      release induced by antigen in cells from guinea pig heart also inhibit pulmonary
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507369
TI  - Epitope-dependent nonreciprocal regulation of IgE and IgG2a antibody formation.
AB  - The antigen dose-dependent production of IgE versus IgG2a antibodies has been
      investigated using keyhole limpet hemocyanin (KLH) and bee venom phospholipase A2
      (PLA2) as antigens. Repeated injections of minute doses (0.1 microgram/mouse) of
      KLH into CBA/J mice lead to relatively high titers of IgE antibodies which are
      gradually reduced in animals that had received higher doses of antigen. In
      contrast, the IgG2a antibody titers are inversely correlated, resulting in low
      titers after repeated injection of 0.1 microgram KLH and high titers after
      repeated doses of 10 micrograms/mouse. With PLA2 as antigen, one finds a
      comparable dose-dependent downregulation of IgE antibody production. In contrast
      to the response to KLH, there is, however, only a marginal IgG2a response at all
      doses tested, and no dose-dependent increase can be found. The data show that an
      inverse regulation of IgE and IgG2a responses is not mandatory. Instead there
      seems to be an additional regulation dictated by antigen epitopes.

PMID- 7507370
TI  - [Seroprevalence of hepatitis C antiviral antibodies in blood donors in N'Djamena
      (Chad)].

PMID- 7507372
TI  - Indocyanine green videoangiography of choroidal neovascular membrane in age
      related macular degeneration.
AB  - Fluorescein angiography is the traditional tool for the detection of choroidal
      neovascularization of age-related macular degeneration. However, some limitations
      exist which impede its efficacy in the detection of subretinal
      neovascularization. Indocyanine green videoangiography is a recently developed
      technique which differs from fluorescein angiography in many ways. We performed
      indocyanine green videoangiography in 18 eyes with occult choroidal
      neovascularization, demonstrated by fluorescein angiography. Sixteen of the 18
      eyes showed an abnormal vessel loop in the early phase of indocyanine green
      videoangiography. In the late phase, all 18 eyes had abnormal dye retention
      around the suspected neovascular area; however, only 12 eyes revealed a distinct
      border of neovascularization. No side effects, such as nausea, vomiting, or
      allergic reactions, were noted in our patients. Advantages and drawbacks of
      indocyanine green videoangiography in comparison with fluorescein angiography are
      discussed.

PMID- 7507371
TI  - [The present status of the conquest of tropical Africa by Pulex irritans
      Linnaeus, 1758].
AB  - Owing to human parasites, two fleas, namely Pulex irritans Linne, 1758 and Tunga
      penetrans (L., 1758) were brought from America to intertropical Africa. The
      conquest of Africa by Pulex irritans, was really effective since the fifties,
      evidently by european strains. Some examples selected in occidental and oriental
      Africa show the reality of this fact. Accordingly, the epidemiological modalities
      in plague's african foci can be strongly changed.

PMID- 7507373
TI  - [Development of medical and biological research in Eastern Siberia].
AB  - The impact of the North conditions on the human body has been studied. There are
      high morbidity and mortality rates, abnormal pregnancy, premature and abnormal
      labors, and congenital malformations in the newborn. A complex of medical and
      prophylactic measures has been worked out to protect human health as a result of
      the studies of the regularities of general and occupational diseases at some
      enterprises in the Far North, Yakutia, and Buryatia.

PMID- 7507374
TI  - [Hygienic aspects of medical and ecological division of Siberia into districts].

PMID- 7507375
TI  - [Demographic aspects of adaptive changes of human immune system in the North].
AB  - The dynamics of an immunotypological structure in migrants in Magadan was studied
      in relation to the duration of residence in the North. The changes were assessed
      by the integrated immune heterogeneity index, the atypic immune status index,
      frequencies of some immune phenotypes, the prevalence of clinical
      immunopathological signs and HLA Class 1 antigen distribution in the groups of
      the examinees. The dynamics of the immunotypological structure of migrants to the
      North was shown to have regular features depending upon the duration of "life in
      the North", some certain time-dependent, qualitative and quantitative
      characteristics. The mechanisms of some changes in the population immune
      structure and their role in the adaptation of northern newcomers to extreme
      ecological conditions are discussed.

PMID- 7507377
TI  - [Mechanisms of adaptation to cold in man and animals].
AB  - The paper presents the results of studies of metabolic processes in the Arctic
      and Antarctic winters, members of Polar expeditions, and inhabitants of the Far
      North. There is a relationship between the metabolism and the length of residence
      in the area of low temperatures, lifestyle, and occupation. The experiments have
      shown changes in the phosphorylizing activity of rat hepatic mitochondria in the
      dynamics of cold adaptation in animals. In addition to the hormonal status and
      antioxidative system, serum lipoproteins were found to determine the response of
      the body to cold exposure. The regulatory role of the lipoprotein components
      apoproteins is discussed in the paper.

PMID- 7507376
TI  - [Gene pool features in the population of the North, genetic processes and health
      status].

PMID- 7507378
TI  - [A concept of promoting health in the population of the circumpolar regions].
AB  - The preservation of human health in polar and circumpolar regions depends mainly
      on the strategy for future development of these regions. The consequences of
      human intervention into northern ecology are irreversible, as in the case of
      greenhouse effect, industrial and atomic pollutions of polar nature, tundra
      devastation, destruction of northern flora and fauna, etc. The ongoing creation
      of large-scale industrial population centers in the North due to newcomers is to
      be stopped. Polar regions are to be used for biospheric reservation and tourist
      sanitary zones, to preserve specific flora and fauna, to provide the rhythms and
      customs necessary to survive in extreme climatic and geophysical conditions of
      high latitudes. The programme for securing man's survival in circumpolar regions
      should comprise several stages of practical measures to provide necessary
      resources and to combine international efforts. The preservation of human health
      should be based on the understanding of the relationship between the health
      status and biospheric processes and the assessment of the role of human
      intervention into polar ecology. A programme facilitating the preservation of
      human health and survival in the North and in the Antarctic should be launched.

PMID- 7507379
TI  - [Medical aspects of migration in the Far East regions].
AB  - A comparative analysis was made of medical and climatic conditions in the south
      of the Far East. Changes in the immune status, lipid peroxidation of blood cell
      membranes, and the antioxidative system were studied during adaptation of adults
      and children who had arrived from Siberia, the European part of Russia, and Far
      East regions. How a standard regional adaptation of the bioimmunological status
      forms was followed up under the conditions of monsoons. Critical periods in
      migrants' adaptation and bioimmunological criteria of development of
      disadaptation conditions are described. A concept of the tense-dynamic type of
      migrants' adaptative bioimmunological reactions under the Far East monsoon
      conditions is proposed.

PMID- 7507381
TI  - [Biorhythms of the lymphoid system and possibilities of immunomodulating
      chronotherapy].
AB  - The paper provides the authors' own data and the data available in the literature
      concerning diurnal rhythms of immunological parameters in the development of
      experimental immunopathological conditions. Desynchronizing these rhythms, a
      change in the light regime is shown to accelerate the time course of the
      development of an autoimmune process in mice. The potentialities of chronotherapy
      of experimental immunodeficiencies with thymic preparations have been studied. It
      is emphasized that chronobiological studies are particularly essential in solving
      the biomedical problems of the Far North with its extreme conditions and a great
      deal of desynchronizing factors.

PMID- 7507380
TI  - [Inflammatory processes in the Far North].

PMID- 7507382
TI  - [Structural and metabolic status of blood lymphocytes in the initial period of
      adaptation stage in man to polar conditions].
AB  - The paper presents the results of studies of the lipid spectrum of blood
      peripheral lymphocytes, the activities of some dehydrogenases in the cells in
      males during their adaptation (up to 1.5 years) to polar conditions. There is
      some dynamics of lymphocytic structural and metabolic parameters, which reflects
      the functional status of lymphocytes and the regulatory effects of the body on
      their status during human adaptation to ecologically unfavourable conditions of
      the Far North.

PMID- 7507384
TI  - [Problems in maintaining and improving health status in small ethnic groups of
      the North].
AB  - The paper provides the materials of studies of the health status, living
      conditions, and environment of small peoples of the North. The conditions of the
      North are shown to have a negative impact on the health status of the population.
      There is a high incidence of tuberculosis among the peoples. The health care
      system in the North should be organized in terms of a comprehensive assessment of
      the health status of various populations of small peoples, the prevalence and
      clinical features of pathological processes and ecological and economical
      factors.

PMID- 7507383
TI  - [The greatest achievements in children and adolescent hygiene in the light of
      development of preventive medicine].

PMID- 7507385
TI  - [History of pediatrics in the Academy of Medical Sciences].

PMID- 7507386
TI  - [Medical and scientific problems in exploring the Far North by man].
AB  - The North is a part of the Earth's biosphere, which is connected with other
      climatic and geographical regions via the common geological and climatic
      processes. The severe natural conditions make the North as an ecological system
      easily vulnerable to anthropogeneous factors. In this connection, the industrial
      development of the northern areas should rely on low-waste and ecologically pure
      technologies. The paper outlines the principles of the system interaction of
      social production, health services, and social security. The medical and
      scientific problems in the development of the Far North by man are formulated in
      general.

PMID- 7507387
TI  - Adoptive immunotherapy of hormone-refractory, stage D2 prostate cancer using ex
      vivo activated autologous T cells (autolymphocyte therapy): results from a pilot
      study.
AB  - There is no effective therapy available for stage D2 prostate cancer once
      patients become refractory to hormonal therapy. In a pilot study, we treated 17
      patients with hormone-refractory stage D2 prostate cancer using autolymphocyte
      therapy, an outpatient form of adoptive immunotherapy in which patients are
      treated with autologous T cells that have been activated ex vivo. Feasibility and
      safety were documented. Transient PSA reductions up to 66% were noted, suggesting
      biological activity. Further studies to test the safety and efficacy of
      autolymphocyte therapy in the treatment of prostate cancer are warranted.

PMID- 7507388
TI  - [Fibromyalgia: pathogenic concepts].

PMID- 7507389
TI  - Benign prostatic hyperplasia: diagnosis and treatment. Agency for Health Care
      Policy and Research.
AB  - This Quick Reference Guide for Clinicians contains highlights from the Clinical
      Practice Guideline of Benign Prostatic Hyperplasia: Diagnosis and Treatment. The
      Benign Prostatic Hyperplasia Guideline Panel, a private-sector panel of health
      care providers, developed the guideline after comprehensively analyzing the
      research literature. As a result, this guideline comprises the most current
      scientific knowledge of the development, diagnosis, and treatment of benign
      prostatic hyperplasia (BPH). The guideline makes specific recommendations to
      identify both the most effective methods for diagnosing BPH and the most
      appropriate treatments for BPH based on patient preference and clinical need. BPH
      affects quality of life and is very rarely a life-threatening disease. Motivation
      to seek active treatment will, for most patients, depend on how much their
      symptoms bother them. Many patients choose a regimen of "watchful waiting." The
      guideline details the relative benefits and harms associated with all diagnostic
      and treatment approaches. Treatment options discussed include watchful waiting,
      alpha blocker and finasteride medications, balloon dilation, and the surgical
      options of transurethral incision, transurethral resection, and open
      prostatectomy.

PMID- 7507390
TI  - Amplification of polyadenylated nontranslated small RNA sequences (POLADS) during
      superinfection correlates with the inhibition of viral and cellular protein
      synthesis.
AB  - The production and the role of POLADS in cells infected with vaccinia virus (VV)
      was studied in doubly infected HeLa and L cells. In cells first infected with VV
      followed by superinfection with UV-irradiated virus (VVuv), referred to as VV +
      VVuv, the course of viral polypeptide synthesis was not significantly altered.
      However, if cells were first infected with VVuv, followed by superinfection with
      VV, referred to as VVuv + VV, both host and viral polypeptide synthesis was
      compromised. Labeling of such infected cells with 3H-adenosine revealed that
      infection with VVuv or VVuv + VV, caused an amplification of incorporation of
      label both in the large and small size class RNAs compared to RNAs obtained from
      a normal infection. On the other hand, labeling of cells with 3H-adenosine which
      were infected with VV + VVuv, caused no significant change in the labeling
      pattern of large and small size class RNAs compared to labeled RNAs from normal
      infection. The large size class RNAs isolated from infection with VVuv or VVuv +
      VV, were translated in the reticulocyte lysate cell-free system much more
      productively compared to the same size RNAs obtained from normal infection. When
      these large size class RNAs were added together with HeLa cell mRNAs to the cell
      free translational system, competition between the two types of mRNAs ensued. The
      small size class RNAs (POLADS) isolated from infection with VVuv or VVuv + VV,
      had little translational activity, but when added together with HeLa cell mRNAs,
      caused a striking inhibition of HeLa cell mRNA translation which was more
      pronounced than the inhibition caused by the small size class RNAs obtained from
      normal infections. POLADS obtained from infection with VV or VV + VVuv inhibited
      HeLa cell protein synthesis to the same extent and were about two times less
      active than the POLADS obtained from infection with VVuv or VVuv + VV. These
      results demonstrate that if cells are first infected with normal virus, the
      superinfecting UV-irradiated virus has little or no effect on the course of VV
      replication, suggesting that the production of POLADS under these conditions is
      regulated. However, when cells are first infected with VVuv, POLADS production is
      amplified to an "abnormal" level, thus, both viral polypeptide synthesis and
      replication of the superinfecting VV is compromised resulting in lower yields of
      virus.

PMID- 7507392
TI  - Bioluminescent symbionts of the Caribbean flashlight fish (Kryptophanaron
      alfredi) have a single rRNA operon.
AB  - Ribosomal RNA (rRNA) operon copy number and gene order were determined for the
      luminous bacterial symbiont of Kryptophanaron alfredi, an anomalopid (flashlight)
      fish, and estimated for the luminous symbionts of 3 other fish families and of 3
      luminous seawater isolates. Compared with the seawater isolates and other fish
      symbionts, the copy number of rRNA genes in the K. alfredi symbiont was radically
      reduced, although gene order appeared conserved among all the strains. The K.
      alfredi symbiont possesses only a single rRNA operon, whereas the other strains
      examined have minimum copy numbers ranging from 8 to 11. No difference in copy
      number was observed between light organ and seawater isolates of the same
      species, or between isolates of the same species from the light organs of 2
      different host families. Thus, the anomalopid symbiosis appears unique among
      characterized light organ symbioses.

PMID- 7507394
TI  - [Morphofunctional state of Purkinje cells in the cerebellum of newborn rats after
      exposure to laser and ionizing radiation].
AB  - Following of local laser (632.8 nm, 6.3 J/cm2) and whole-body 6.37 Gy gamma-ray
      exposures of new-born rats the contrast changes of morphometrical indices, RNA
      amount, and chromatophilia of Purkinje cells in the cerebellum were seen. The
      preliminary laser exposure of new-born rat cerebellum artially increased activity
      of karyogene structures of the cerebellum cells which were inhibited by 6.37 Gy
      gamma-rays.

PMID- 7507393
TI  - [DNA synthesis and DNA and RNA content in lymphocytes with x-ray irradiation in
      guinea pigs].
AB  - A study was made of the effect of X-radiation (2.6 and 180.6 mC/kg) on
      proliferative activity and DNA and RNA content of guinea pig lymphocytes. There
      was a considerable decrease in proliferative activity and a slight increase in
      DNA and RNA content in 24 h after irradiation.

PMID- 7507395
TI  - [Local differences in the tissue basophils of the cerebral dura mater in the
      rat].
AB  - Tissue basophils (TB) were investigated in 5 (occipital, right and left frontal
      and parietal) areas of the dura mater in 75 albino rats by histological and
      histochemical methods. Local distinctions in the structure, distribution and
      functional activity of cells were found. The greatest concentration of TB
      revealed by staining with methylene blue, cytochrome oxidation reaction and with
      glyoxylic acid was found in the frontal areas and the lowest concentration in the
      occipital areas of the mater. The amount of cells with activity of succinic
      dehydrogenase in the occipital area was, on the contrary, 11-13 times greater
      than their amount in the frontal and parietal areas of the mater. The local
      distinctions of TB marked with ATPase are not so considerable and those of
      alkaline phosphatase were not significant. The frontal areas (right and left)
      were found to have the greatest concentration of the degranulated forms of TB as
      well.

PMID- 7507396
TI  - Speech and language therapy for aphasia.
AB  - More information into the natural course of dysphasia has improved information
      related to prognosis. An increased understanding regarding the underlying complex
      basis of language and communication leads to interesting intellectual debate and
      confronts the previously more simplistic approaches to assessment and remediation
      without necessarily assisting by replacing these with coherent and practical
      methods of management of this disability in context.

PMID- 7507391
TI  - Comparative investigation of the effects of the immunosuppressants cyclosporine
      A, cyclosporine G, and FK-506 on platelet activation.
AB  - We have determined that ADP-induced platelet aggregation and secretion are
      enhanced by preincubation of human platelets with the immunosuppressant
      cyclosporine A (CSA) (see accompanying article by Naik et al., 1993). In the
      present report we compare the effects of CSA with two other potent
      immunosuppressants, cyclosporine G (CSG), an analogue of CSA, and FK-506, on
      platelet activation. Preincubation of platelets with either CSA, CSG, or FK-506
      resulted in platelets which exhibited hyperaggregability when stimulated by ADP.
      CSG produced the lowest degree of hyperaggregation, whereas FK-506 produced the
      highest at an equivalent concentration. All three compounds enhanced the
      secretion of serotonin, with FK-506 producing the highest degree of serotonin
      release and CSG producing the lowest amount. Platelet hyperaggregation and
      enhanced secretion were both time- and dose-dependent. Comparative studies
      performed with CSA and CSG indicated that a short preincubation period with CSA
      (2.5 min) resulted in a 90% enhancement of ADP-induced platelet aggregation,
      whereas CSG enhancement was only 20%. At a concentration of 600 ng/ml, CSA
      produced 120% enhancement of ADP-induced platelet aggregation, whereas CSG
      produced only a 30% enhancement. Several potential mechanisms responsible for the
      enhanced ADP-induced aggregation and secretion were investigated. Determination
      of the binding of two radiolabeled probes directed against the fibrinogen
      receptor, fibrinogen itself, and a monoclonal antibody (M.Ab.G10) revealed that
      the binding of fibrinogen to ADP-stimulated platelets was enhanced by 50%
      following the preincubation of platelets with 600 ng/ml CSA. Smaller, yet
      significant enhancement occurred in the presence of CSG. Similar results were
      obtained when M.Ab.G10 was used. Preincubation of platelets with 600 ng/ml CSA or
      CSG resulted in 60% and 30% increase in total protein kinase C activity,
      respectively, following the addition of ADP. In conclusion, this study has
      determined that preincubation of platelets with CSA or FK-506 (CSG, to a smaller
      extent) results in significant enhancement of ADP-induced platelet aggregation
      and secretion. The hyperaggregation and hypersecretion observed may be due to an
      enhanced expression of fibrinogen receptors on the platelet surface resulting
      from an increase in protein kinase C activity.

PMID- 7507397
TI  - Neuronal damage induced by beta-N-oxalylamino-L-alanine, in the rat hippocampus,
      can be prevented by a non-NMDA antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo(F)quinoxaline.
AB  - The neurotoxin beta-N-oxalylamino-L-alanine (BOAA), found in Lathyrus sativus
      seeds, is thought to be the causative agent of neurolathyrism. We have
      investigated the in vivo mechanism of action of BOAA by focal injection (1
      microliter) in the dorsal hippocampus of male Wistar rats and comparing the
      pathological outcome with the effects of injections (1 microliter) of alpha-amino
      3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), kainate (KA) or N-methyl-D
      aspartate (NMDA). Cellular damage induced by the excitatory amino acids in the
      pyramidal (CA1-CA4) and dentate granule neurones (DG) was assessed histologically
      24 h after the injection. The study shows that BOAA (50 nmol) induces hippocampal
      toxicity with a highly selective pattern of regional cellular damage. The CA1,
      CA4 and DG subfields show 70-90% neuronal injury whereas CA2 and CA3 show only
      minimal damage. This pattern of cellular damage is similar to that induced by
      AMPA (1 nmol) and NMDA (25 nmol) but not KA (0.5 nmol). BOAA-induced
      neurotoxicity is prevented in a dose-dependent manner by focal co-injection of
      the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo(F)quinoxaline (NBQX) (1-25 nmol) but not by a dose of MK-801 (3 mg/kg i.p.)
      which is neuroprotective against an injection of NMDA. Delayed focal injections
      of NBQX (25 nmol) up to 2 h after the BOAA injection result in a significant
      protection of all pyramidal and granular cell regions. These results indicate
      that the in vivo hippocampal toxicity of BOAA is mediated by AMPA receptors
      rather than by KA or NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507398
TI  - Inferior olive serotonin and norepinephrine levels during development in the
      genetically dystonic rat.
AB  - The dystonic (dt) rat is an autosomal recessive mutant with a motor syndrome that
      shares several features with idiopathic torsion dystonia in humans. In the dt
      rats, marked biochemical and physiological abnormalities have been localized to
      the olivo-cerebellar system. At the pharmacological level, the dt rats exhibit
      enhanced sensitivity to the behavioral effects of serotonergic (5HT) agonists,
      including quipazine, a drug that activates the neurons of the inferior olive
      (IO). High performance liquid chromatography with electrochemical detection was
      used to assay 5-HT, 5-hydroxyindoleacetic acid (5HIAA), and norepinephrine (NE)
      in micropunches of the IO in normal and dt rats at 14, 18 and 22 days of age.
      Samples of the rostral frontal lobes were used as internal controls. Significant
      age-dependent effects were seen on 5-HT and 5-HIAA levels in the IO, but not the
      frontal cortex, in both groups. Although both groups reached similar 5-HT levels
      by postnatal day 22, a significant interaction effect between age and phenotype
      indicated a difference in the pattern of development. Administration of quipazine
      (10 mg/kg, IP) to 18-day-old normal and dt rats 1 h prior to sacrifice caused
      significant reductions in NE, 5-HIAA and the ratio of 5-HIAA to 5-HT; however, no
      phenotypic differences were detected. The findings do not suggest that the
      differential behavioral responses to 5-HT agonists seen in normal and dt rats are
      the result of global abnormalities in 5-HT systems, nor do they suggest the
      presence of presynaptic defects in the IO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507399
TI  - Effect of chronic DDC treatment on LHRH and substance P amidation processes in
      the rat.
AB  - We examined the effects of chronic diethyldithiocarbamate (DDC) treatment on the
      concentrations of methionine-enkephalin, mature and unamidated forms (-Gly) of
      luteinizing hormone releasing hormone (LHRH) and substance P (SP) in various
      regions of the central nervous system (CNS). Chronic DDC treatment resulted in
      elevations of LHRH-Gly like immunoreactivity in the preoptic area (POA) and the
      medial basal hypothalamus (MBH), as well as elevations in SP-Gly like
      immunoreactivity in all areas of the CNS examined. Castration altered the ratios
      of SP-G-like/SP-like immunoreactivity in the pons, and LHRH-Gly like
      immunoreactivity in the MBH. Met-enkephalin concentrations were significantly
      elevated in the pons and medulla of intact DDC-treated animals, and in the POA of
      both intact- and castrated DDC-treated animals. Results demonstrate that it is
      possible to detect basal levels of unamidated LHRH and SP in many areas of the
      CNS, with ratios of unamidated/amidated peptides representing a unique and
      sensitive method for determining altered posttranslational processing of these
      transmitters, especially under altered endocrine states such as castration.
      Pharmacological blockade of terminal enzymatic processing of these peptides may
      be useful in studying upstream regulatory events in peptidergic neurons.

PMID- 7507400
TI  - Automatic display of RNA secondary structures.
AB  - A set of programs written in C language with the GL library and under UNIX has
      been developed for generating compact, pleasant and non-overlapping displays of
      secondary structures of ribonucleic acids. The first program, rnasearch,
      implements a new search procedure that dynamically rearranges overlapping
      portions of the two-dimensional drawing while preserving clear and readable
      displays of the two-dimensional structure. The algorithm is fast (the execution
      time for the command rnasearch is 38.6 s for the 16S rRNA of Escherichia coli
      with 1542 bases), accepts outputs from two-dimensional prediction programs and
      therefore allows for rapid comparison between the various two-dimensional folds
      generated. A second program, rnadisplay, allows the graphical display of the
      computed two-dimensional structures on a graphics workstation. Otherwise, it is
      possible to obtain a paper output of the two-dimensional structure by using the
      program print2D which builds a Postscript file. Moreover the two-dimensional
      drawing can be labelled for representing data coming from chemical modifications
      and/or enzymatic cleavages. Application to a few secondary structures such as
      RNaseP, 5S rRNA and 16S rRNA are given.

PMID- 7507402
TI  - Differential expression of keratin 5 gene in non-tumorigenic and tumorigenic rat
      bladder cell lines.
AB  - In this study, we attempted to find a gene or genes which were differentially
      expressed between a non-tumorigenic rat bladder cell line and a highly
      tumorigenic/metastatic bladder carcinoma cell line that was derived from the
      former after treatment in vitro with N-methyl-N-nitrosourea. We cloned a rat
      keratin 5 cDNA by a differential hybridization technique and found that all of
      the non-tumorigenic cells (7/7) and normal bladder tissue expressed keratin 5,
      but most of the tumorigenic cells (8/10) did not express keratin 5. Furthermore,
      in a spontaneously transformed cell line, keratin 5 expression was lost during
      the transformation process. These results suggest that loss of keratin 5
      expression is closely associated with acquisition of a tumorigenic phenotype by
      rat bladder non-tumorigenic cells.

PMID- 7507401
TI  - Combined antineoplastic and antiretroviral therapy for patients with Hodgkin's
      disease and human immunodeficiency virus infection. A prospective study of 17
      patients. The Italian Cooperative Group on AIDS and Tumors (GICAT).
AB  - BACKGROUND: The optimal therapeutic approach for patients with Hodgkin's disease
      (HD) and human immunodeficiency virus (HIV) infection is unknown. In an attempt
      to improve the results obtained with standard chemotherapy and to decrease the
      occurrence of opportunistic infections (OI) during chemotherapy and follow-up
      observed in a previous experience, the authors designed a prospective combined
      antineoplastic and antiretroviral approach. METHODS: Between March 1989 and March
      1992, 17 consecutive previously untreated patients (median age, 30 years) with HD
      and HIV infection were enrolled. They had Stage III and IV or Stage I and II
      disease with adverse prognostic factors. The median CD4+ cell count was
      184/microliters. Patients were stratified in two groups and treated accordingly.
      Group A was made up of patients with an Eastern Cooperative Oncology Group (ECOG)
      performance status (PS) of less than 3 and without OI. These patients received
      epirubicin 70 mg/m2 intravenously on day 1, bleomycin 10 mg/m2 IV on day 1, and
      vinblastine 6 mg/m2 IV on day 1 (regimen EBV). Group B was made up of patients
      with PS of 3 or greater or previous OI who had received a 50% reduced dose of
      epirubicin and vinblastine and a full dose of bleomycin. Courses were repeated
      every 21 days for six cycles. Zidovudine was given at the dose of 500 mg/day from
      the beginning of chemotherapy in Group B and after the third cycle in Group A.
      RESULTS: Overall, 14 of 17 (82%) patients had an objective response and 9 of 17
      (53%) achieved a complete remission (CR) of disease for a median duration of 20
      months. Toxicity was moderate with Grade 3-4 leukopenia in eight patients and
      Grade 3 thrombocytopenia in one patient. Thirteen of 17 patients received
      zidovudine as planned with a median duration of 9 months. Only one patient had OI
      during or after chemotherapy (median follow-up, 11 months). No worsening of HIV
      markers during the combined therapy was seen, with the median CD4+ cell count
      before and after therapy being 184/microliters and 203/microliters, respectively.
      The median survival time was 11 months, with an actuarial survival rate of 48% at
      36 months. The median survival time for the nine patients with CR has not been
      reached at the time of this analysis. CONCLUSIONS: These results revealed the
      feasibility and the activity of the combination of EBV regimen and zidovudine.
      Objective response rate seems similar to those previously observed in patients
      receiving standard chemotherapy, but only one patient had OI, and this compares
      favorably with the 16 OI observed in 28 patients treated with standard
      chemotherapy (6% versus 57%) in the authors' previous experience. Thus, it seems
      that the addition of antiretroviral therapy to the EBV regimen decreased the
      occurrence of OI during chemotherapy or follow-up.

PMID- 7507403
TI  - Electrochemotherapy--a novel method of cancer treatment.
AB  - A critical review is presented on a novel method of treating cancer by a
      combination of an electric field with chemotherapeutic agents. The work described
      here summarizes the current state of the technique known as electrical impulse
      chemotherapy (EIC) or electrochemotherapy (ECT). The review discusses in vitro
      results with specific cell lines, in vivo work on animals and clinical results on
      patients with squamous cell carcinomas of the head and neck. In all cases, it has
      been found that uptake of various drugs by the tumor cells can be increased
      markedly by EIC/ECT. Partial responses and complete cures have been observed
      without any damaging side-effects, provided the field strength is kept
      sufficiently low. ECT followed by injection of a low dose of interleukin-2 (IL-2)
      or IL-2 secreting cells has shown better results than ECT alone. There appears to
      be a systemic effect and a strong indication that an immune response may be
      elicited by this method of treatment. Finally, we discuss the challenges involved
      in hardware requirements for EIC/ECT and its future prospects for both drug
      delivery and gene therapy.

PMID- 7507404
TI  - Preclinical and clinical aspects of biomodulation of 5-fluorouracil.
AB  - Although single agent 5-FU has for many years been the standard therapy for
      advanced colorectal malignancies, a number of recent clinical trials show higher
      response rates with biomodulation of 5-FU by several different agents. In
      general, trials of leucovorin, methotrexate, interferon, and PALA given in
      biomodulatory doses and sequences with 5-FU have demonstrated comparable response
      rates over a broad range. However, in the absence of controlled direct
      comparative phase III trials, final judgement on clinical superiority of a
      particular regimen must be reserved. Nevertheless, on the basis of current data,
      certain approaches appear promising and warrant further investigation. Compared
      to single agent 5-FU, survival benefit has been demonstrated with both low and
      high dose leucovorin/5-FU regimens and response rates in the 20-50% range appear
      reproducibly higher than those of 5-FU alone. Low dose and either continuous
      infusion or repetitive dosing of leucovorin, as well as the effect of treatment
      sequence and intervals between drugs, require additional investigation. When
      given 20-24 h before 5-FU, methotrexate achieves response rates similar to
      leucovorin modulated 5-FU, but the potential role of rescue leucovorin used in
      many of the trials makes definitive interpretation difficult. Interferon/5-FU
      regimens attaining response rates of 30-40% are promising but need to be
      carefully and rationally designed. Low dose PALA with effective doses of 5-FU
      achieving responses in 35-45% of patients represent a marked improvement in
      earlier trials of high dose PALA, but additional studies with higher doses not
      compromising 5-FU dose intensity should be considered. Certainly, the concomitant
      use of multiple modulating agents also needs further investigation. While many
      such trials already performed attained results no better than single agent
      biomodulation, the preliminary results obtained by Grem and colleagues with
      IFN/LV/5-FU in untreated patients, and by Conti et al. using TMTX/LV/5-FU in
      previously treated patients are encouraging. Further understanding of the
      mechanisms of action and interaction of modulating agents should allow additional
      rational combinations to be explored clinically. Cisplatin biomodulation of 5-FU
      has been studied in gastrointestinal and head and neck malignancies achieving
      excellent results in the latter group. Preclinical evidence exists which
      suggests, however, that 5-FU modulation of cisplatin may be more effective,
      especially when 5-FU is administered 24 h or more before cisplatin. Clinical
      investigation of this sequence is currently lacking. Data to support the clinical
      promise of AZT, IdUrd, uridine, and the benzylacyclouridines are not yet
      available, although preclinical and preliminary clinical studies are promising.

PMID- 7507405
TI  - Cellular mechanisms of estrogen- and dopamine-induced control of glandular
      kallikrein in the anterior pituitary of the rat.
AB  - Glandular kallikrein (GK, a trypsin-like serine protease) exhibits estrogen
      induction and dopamine repression in rat pituitary lactotrophs. Steroid induction
      may reflect primary actions to increase selectively the synthesis of specific
      proteins, or may be part of broad cellular responses secondary to steroid-induced
      phenotype transitions. This study examined the cellular mechanisms underlying
      estrogen and dopaminergic control of lactotroph GK using a quantified
      immunocytochemical approach. Pituitaries from ovariectomized rats exhibited
      little GK staining. Estradiol treatment for 10 days produced dose-dependent
      increases in pituitary mass, the percentage of lactotrophs (indicating lactotroph
      proliferation) and the percentage of GK-positive cells. Also, GK staining
      intensity was dependent upon estradiol dose, increasing 4-fold between 5
      micrograms and 50 micrograms/48 h. Dopamine receptor blockade with haloperidol
      (2.5 mg/kg/24 h) elicited weak GK immunostaining in 46% of the lactotrophs in the
      absence of estradiol, and markedly potentiated GK staining intensity elicited
      with low but not high doses of estradiol. The results suggest that GK induction
      is a primary estrogen effect, and is not secondary to a phenotype transition: the
      induction is enhanced by estrogen-induced lactotroph proliferation. Dopaminergic
      systems strongly inhibit GK induction by low estradiol levels. This dopaminergic
      modulation may shift the induction of lactotroph GK to physiological events
      associated with high estradiol levels or low dopaminergic tone.

PMID- 7507406
TI  - Changes in cell adhesion and cell proliferation are associated with expression of
      tissue non-specific alkaline phosphatase.
AB  - Tissue non-specific alkaline phosphatase is a membrane-bound glycoprotein enzyme
      which is characterized by its phosphohydrolytic, protein phosphatase, and
      phosphotransferase activities. This enzyme is distributed virtually in all
      mammalian tissues, particularly during embryonic development. Its expression is
      stage-specific and can be demonstrated in the developing embryo as early as the 2
      cell stage. It has been suggested that tissue non-specific alkaline phosphatase
      might play a role in tissue formation. In the study reported here, a gene
      transfer approach was employed to investigate possible roles for this enzyme by
      inserting the cDNA for rat tissue non-specific alkaline phosphatase into CHO and
      LLC-PK1 cells. Permanently transfected cell-lines expressing varying levels of
      alkaline phosphatase were established. The data showed that functional enzyme was
      expressed in the transfected cells. Cell spreading and attachment were enhanced
      in transfected CHO cells expressing high levels of tissue non-specific alkaline
      phosphatase but not in the LLC-PK1 cells. Further, in CHO cells, proliferation
      was shown to be inversely proportional to the level of the tissue non-specific
      alkaline phosphatase expression. Homotypic cell association was demonstrated in
      both alkaline phosphatase-positive and alkaline phosphatase-negative cells in
      both CHO and LLC-PK1 cell-lines. Taken together, these findings suggest that in
      addition to a role in mineralization of bone, tissue non-specific alkaline
      phosphatase might also play a role in other cell activities, including those
      related to differentiation, such as cell-cell or cell-substrate interaction and
      proliferation.

PMID- 7507407
TI  - Calcitonin gene-related peptide expression at endplates of different fibre types
      in muscles in rat hind limbs.
AB  - Calcitonin gene-related peptide (CGRP) occurs only in some motoneurons. In this
      study, the presence of CGRP in motor endplates in relation to muscle fibre types
      was examined in slow (soleus muscle) and fast [tibialis anterior (TA) and
      extensor digitorum longus (EDL)] leg muscles of the rat. CGRP was detected by use
      of immunohistochemical methods, and staining for the mitochondrial-bound enzyme
      NADH-TR was used for demonstration of fibre types. The fibres showing low NADH-TR
      activity were interpreted as representing IIB fibres. All such fibres located in
      the superficial portion of TA were innervated by endplates displaying CGRP-like
      immunoreactivity (LI), whereas in the deep portion of TA some of these fibres
      lacked CGRP-LI at their endplates. Thirty per cent of the IIB fibres in EDL
      showed CGRP-LI at the endplates. All fibres in TA and EDL displaying high NADH-TR
      activity and interpreted as type-IIA fibres, lacked CGRP-LI in their motor
      innervation. One third of the fibres with intermediate NADH-TR activity in TA
      exhibited CGRP-LI at their endplates, whereas in EDL only few such fibres
      displayed CGRP-LI in the endplate formation. These fibres are likely to belong to
      type-IIX or type-I motor units. CGRP-LI was very rarely detected at the endplates
      in the soleus muscle. These observations show that distinct differences exist
      between the slow muscle, soleus, and the fast muscles, TA and EDL, but that there
      are also differences between the different types of fibres in TA and EDL with
      respect to presence of CGRP-LI at the endplates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507408
TI  - Developmental changes in the cell columns and trophoblastic shell of the macaque
      placenta: an immunohistochemical study localizing type IV collagen, laminin,
      fibronectin and cytokeratins.
AB  - Developmental changes in the organization of cells and extracellular matrix in
      the cell columns and trophoblastic shell of macaque placentas have been examined
      between 37 days of gestation and term. Between 37 and 53 days a thickened
      basement membrane developed between the trophoblast cells of the proximal cell
      columns and the mesenchymal cores of contiguous anchoring villi. This layer
      stained strongly for type IV collagen and laminin, but weakly for fibronectin.
      Large "lakes" of extracellular matrix immunoreactive for all 3 of these antigens
      were present in the distal columns, while smaller amounts were distributed
      between cells of the proximal columns. During this period the trophoblast cells
      in the proximal shell reorganized, forming strands of cells that were separated
      by bands of matrix immunoreactive for type IV collagen, laminin, and fibronectin.
      Staining for these antigens decreased abruptly at the junction between fetal and
      maternal tissues. Between 66 and 104 days the thick basement membrane of the
      proximal columns persisted, but stained only weakly for each of the 3
      extracellular matrix antigens. The large lakes of matrix in the distal columns
      characteristic of earlier stages gradually disappeared. The cell columns became
      progressively shorter and the tips of the anchoring villi became embedded in the
      trophoblastic shell. The matrix of the shell decreased in immunostaining
      intensity except for narrow rims around the trophoblast cells. Gestational ages
      later than 104 days showed few additional changes in the distribution of the
      matrix antigens or cell organization of the columns and shell. The thick basement
      membrane-like layer persisted to term although it continued to stain weakly for
      the 3 matrix antigens. The distal ends of most anchoring villi were embedded in
      the trophoblastic shell. The developmental changes in the organization of the
      columns and shell may be related to changes in placental growth rate.

PMID- 7507409
TI  - Colocalization of vasoactive substances in the endothelial cells of human
      umbilical vessels.
AB  - Human umbilical vessels are unique in lacking any innervation; thus endothelial
      cells may play the major role in local control and regulation of the blood flow.
      In the present study, we examined ultrathin sections of cultured human umbilical
      vein endothelial cells and tissue preparations of umbilical vein and artery,
      immunostained by the post-embedding colloidal gold double-labelling technique. We
      observed colocalization of atrial natriuretic peptide and neuropeptide Y, as well
      as colocalization of atrial natriuretic peptide and neuropeptide Y with other
      vasoactive substances, namely, vasoactive intestinal peptide, substance P,
      calcitonin gene-related peptide and arginine vasopressin. The functional
      significance of the colocalization of these vasoactive substances in the human
      umbilical vessel endothelial cells is discussed.

PMID- 7507410
TI  - Ultrastructural localization of NADPH-diaphorase and colocalization of nitric
      oxide synthase in endothelial cells of the rabbit aorta.
AB  - This is the first report on the ultrastructural pattern of distribution of
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in endothelial
      cells, using the rabbit aorta, and its colocalization with the neuronal isoform
      (type I) of nitric oxide synthase. About 30% of the endothelial cells showed a
      positive reaction for NADPH-d compared to about 6% for nitric oxide synthase
      immunoreactivity. Simultaneous double histochemical-immunocytochemical labelling
      procedures indicate that all of the cells displaying nitric oxide synthase
      positive reactivity also contained NADPH-d; the remainder of NADPH-d-positive
      endothelial cells were negative for this isoform of nitric oxide synthase. Nitric
      oxide synthase-immunogold labelling was mostly associated with free ribosomes,
      while NADPH-d activity was distributed largely in patches in the cytoplasm and in
      association with the cell membrane.

PMID- 7507412
TI  - Two collagen-binding domains of vitronectin.
AB  - Vitronectin is a cell-adhesive glycoprotein present in animal blood and
      extracellular matrix. To establish the molecular basis of vitronectin
      interactions with extracellular matrix macromolecules, the binding site of
      vitronectin to collagen has been investigated. Vitronectin fragments obtained by
      formic acid cleavage were separated by heparin-affinity chromatography followed
      by gel filtration chromatography. The collagen-binding activity of the fragments
      was assayed in terms of inhibitory activity on the binding of 125I-vitronectin to
      immobilized collagen. There were two groups of collagen-binding fragments. One
      group consisted of 5 heparin-binding fragments with estimated molecular masses of
      12 kDa, 14 kDa, 16 kDa, 18 kDa, and 19 kDa in SDS-polyacrylamide gel
      electrophoresis. The other group consisted of 2 heparin-nonbinding fragments
      migrating at 18 kDa and 40 kDa. These results indicate that there are two
      collagen-binding sites in the vitronectin molecule; one located close to the
      heparin-binding domain in the COOH-terminal half and the other located in the NH2
      terminal half of vitronectin.

PMID- 7507411
TI  - Traffic signals for lymphocyte recirculation and leukocyte emigration: the
      multistep paradigm.

PMID- 7507413
TI  - Biological potential of basophilic hepatocellular foci and hepatic adenoma
      induced by the peroxisome proliferator, Wy-14,643.
AB  - The biological potential of hepatic foci and tumors induced by peroxisome
      proliferators such as Wy-14,643 has been poorly characterized. In this study,
      male F-344 rats (n = 20/group/time point) were fed Wy-14,643 (0.1%) for 22, 37 or
      52 weeks ('W-22', 'W-37' or 'W-52' respectively). At each time point some rats
      were killed and additional Wy-14,643-fed rats were switched to basal diet (Wy
      14,643/'stopped') for up to 104 weeks (referred to as 'W-22/S', 'W-37/S' and 'W
      52/S'). Homogeneous basophilic foci, but not clear cell foci, increased in number
      and size in W-37 and W-52 rats. In W-37/S rats, clear cell foci replaced
      basophilic foci as the most frequent phenotype. In serial section overlays,
      adenosine triphosphatase deficient foci accounted for only 16% of basophilic foci
      in W-52 rats and 16% of clear cell foci in W-37/S rats at 52 weeks. The
      replication of basophilic foci of W-37 rats was markedly increased (focal
      labeling index, FLI = 61.8% versus non-focal labeling index, LI = 11.4%; control
      LI = 0.8%). Clear cell foci from W-37/S rats at 52 weeks had a FLI of 1.6% (non
      focal LI = 0.6%). Hepatocellular adenomas were increased in W-37 (11/20 rats and
      0.8 tumors/rat) and W-52 groups (19/20 rats and 2.8 tumors/rat). Prevalence of
      hepatocellular carcinomas was elevated in W-52 rats (6/20 rats) but not in W-22
      or W-37 rats. Following removal of Wy-14,643, prevalence of animals with
      malignant, metastatic hepatocellular carcinomas in W-52/S rats was similar to the
      prevalence in W-52 rats. However, Wy-14,643-induced adenomas completely regressed
      in W-37/S and W-52/S groups. In summary, significant morphological continuity
      between highly proliferative basophilic foci and hepatocellular tumors was
      identified, emphasizing the superiority of basophilia as a marker for lesions
      leading to development of hepatocellular neoplasia in rats fed Wy-14,643. An
      important biological distinction was noted between regressive hepatic adenomas
      and progressive hepatocellular carcinomas induced by a peroxisome proliferator.

PMID- 7507414
TI  - Regulation of vascular cell adhesion molecule-1 and intercellular adhesion
      molecule-1 in human vascular smooth muscle cells.
AB  - Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1
      (ICAM-1), and E-selectin are inducible proteins involved in cell-cell adhesion.
      Immunohistochemical studies have indicated that human atherosclerotic plaques
      contain smooth muscle cells (SMCs) that express ICAM-1 and VCAM-1. Recently, we
      demonstrated that SMCs in culture express a functionally active cytokine
      inducible ICAM-1. SMCs and mononuclear cells participate in the local
      accumulation of cytokines and related growth factors in atherosclerotic lesions.
      Therefore, we determined the effects of different cytokines and growth factors on
      mRNA content and cell surface expression of VCAM-1, ICAM-1, and E-selectin in
      cultured human aortic SMCs by Northern blotting, quantitative polymerase chain
      reaction amplification, and immunofluorescence flow cytometry. Under basal
      conditions of cultivation, both VCAM-1 mRNA and membrane expression of VCAM-1
      were low and were induced very little by interleukin-1 beta (100 U/mL). Platelet
      derived growth factor or transforming growth factor-beta decreased VCAM-1 mRNA
      basal expression. Treatment of SMCs with tumor necrosis factor-alpha (TNF-alpha)
      led to an increase in both VCAM-1 mRNA and cell surface expression for VCAM-1 in
      a dose- and time-dependent manner. Interferon-gamma induced a weak increase in
      VCAM-1 mRNA expression, with no synergistic effect on the stimulation by TNF
      alpha. Various differences were noted between the expression of ICAM-1 and VCAM-1
      genes, because interleukin-1 beta induced substantial amounts of ICAM-1 but not
      VCAM-1. The addition of interferon-gamma delays the time at which peak expression
      of ICAM-1 in response to TNF-alpha stimulation occurs. Under our conditions, we
      did not detect any expression of E-selectin by SMCs. These results suggest that
      cytokines regulate VCAM-1 and ICAM-1 expression on arterial SMCs and could play
      an important role in the pathophysiology of inflammatory and immune processes in
      atherosclerosis.

PMID- 7507415
TI  - Inhibition of inducible nitric oxide synthase in macrophages by oxidized low
      density lipoproteins.
AB  - Uptake of oxidized low-density lipoprotein (LDL) by monocyte/macrophages to form
      "foam" cells has been implicated in atherogenesis. Activated monocyte/macrophages
      synthesize nitric oxide (NO) from L-arginine. NO is cytotoxic, antiproliferative,
      and a vasodilator that inhibits platelet and monocyte adhesion. NO synthase mRNA,
      protein, and enzyme activity were induced in J774.A1 macrophages activated with
      lipopolysaccharide and gamma interferon. When macrophages were incubated with
      oxidized LDL for 24 hours and activated, there was a dose- and time-dependent
      inhibition of NO synthesis, assessed as nitrite accumulation in the media. When
      activated cells were incubated with nontoxic doses of lipoprotein (25
      micrograms/mL), neither native LDL nor acetyl LDL inhibited NO production,
      whereas oxidized LDL produced 50% inhibition. Levels of enzyme protein were
      unchanged by Western blot. Inhibition was a function of the degree of oxidation
      of LDL but was independent of cholesteryl esterification by the cells.
      Incubations of oxidized LDL with cells that had been pretreated with dextran
      sulfate or cytochalasin B yielded no evidence that inhibition was dependent on
      the scavenger receptor or directed endocytosis. Kinetic studies of inducible NO
      synthase from J774.A1 cells that were incubated with increasing doses of oxidized
      LDL indicated a pattern of noncompetitive inhibition. Inhibition of the enzyme
      was produced by lipids extracted from oxidized LDL but not by lipids extracted
      from native LDL. Because phosphatidylcholine (PC) is converted to
      lysophosphatidylcholine (LPC) during the oxidation of LDL, the effects of LPC
      were investigated. PC vesicles containing LPC did not inhibit enzyme activity but
      produced modest reductions in nitrite accumulation from cells. In contrast, PC
      vesicles had no significant effect. The data indicate that oxidized LDL lipid
      inhibits the activity of inducible NO synthase in activated macrophages. NO
      production by this enzyme and its inhibition by oxidized LDL lipid may influence
      cell-to-cell interactions and vasomotor tone in atherosclerotic blood vessels.

PMID- 7507417
TI  - Chronic exercise in dogs increases coronary vascular nitric oxide production and
      endothelial cell nitric oxide synthase gene expression.
AB  - Recently, we have shown that chronic exercise increases endothelium-derived
      relaxing factor (EDRF)/nitric oxide (NO)-mediated epicardial coronary artery
      dilation in response to brief occlusion and acetylcholine. This finding suggests
      that exercise can provide a stimulus for the enhanced production of EDRF/NO, thus
      possibly contributing to the beneficial effects of exercise on the cardiovascular
      system. Therefore, the purpose of the present study was to examine whether
      chronic exercise could influence the production of NO (measured as the stable
      degradation product, nitrite) and endothelial cell NO synthase (ECNOS) gene
      expression in vessels from dogs after chronic exercise. To this end, dogs were
      exercised by running on a treadmill (9.5 km/h for 1 hour, twice daily) for 10
      days, and nitrite production in large coronary vessels and microvessels and ECNOS
      gene expression in aortic endothelial extracts were assessed. Acetylcholine (10(
      7) to 10(-5) mol/L) dose-dependently increased the release of nitrite (inhibited
      by nitro-L-arginine) from coronary arteries and microvessels in control and
      exercised dogs. Moreover, acetylcholine-stimulated nitrite production was
      markedly enhanced in large coronary arteries and microvessels prepared from
      hearts of dogs after chronic exercise compared with hearts from control dogs. One
      potential mechanism that may contribute to the enhanced production of nitrite in
      vessels from exercised dogs may be the induction of the calcium-dependent ECNOS
      gene. Steady-state mRNA levels for ECNOS were significantly higher than mRNA
      levels for von Willebrand's factor (vWF, a specific endothelial cell marker) and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a constitutively expressed gene)
      in exercised dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507416
TI  - Molecular determinants of reperfusion-induced leukocyte adhesion and vascular
      protein leakage.
AB  - The adherence and emigration of leukocytes have been implicated as a rate
      limiting step in the microvascular dysfunction associated with reperfusion of
      ischemic tissues. The objective of the present study was to define the relation
      between leukocyte-endothelial cell adhesion and albumin leakage in rat mesenteric
      venules exposed to ischemia and reperfusion (I/R). Leukocyte adherence and
      emigration as well as albumin extravasation were monitored in single post
      capillary venules using intravital fluorescence microscopy. Ischemia (0, 10, 15,
      or 20 minutes) was induced by complete occlusion of the superior mesenteric
      artery, and all parameters were monitored for 30 minutes after reperfusion. The
      magnitude of the leukocyte adherence and emigration and albumin leakage elicited
      by I/R was positively correlated with the duration of ischemia. The albumin
      leakage response was also highly correlated with the number of adherent and
      emigrated leukocytes. Monoclonal antibodies against the adhesion glycoproteins
      CD18, CD11b, intercellular adhesion molecule-1 (ICAM-1) (at 10 and 30 minutes),
      and L-selectin (at 10 minutes), but not P- or E-selectin, reduced I/R-induced
      leukocyte adherence and emigration as well as albumin leakage. Platelet-leukocyte
      aggregates were formed in postischemic venules; the number of aggregates was
      reduced by antibodies against P-selectin, CD11b, CD18, and ICAM-1, but not E- or
      L-selectin. These results indicate that reperfusion-induced albumin leakage is
      tightly coupled to the adherence and emigration of leukocytes in postcapillary
      venules. This adhesion-dependent injury response is primarily mediated by
      CD11b/CD18 on activated neutrophils and ICAM-1 on venular endothelium and appears
      to require L-selectin-dependent leukocyte rolling.

PMID- 7507418
TI  - Altered morphology of vegetative amoebae induced by increased expression of the
      Dictyostelium discoideum ras-related gene rap1.
AB  - The rap1 gene of Dictyostelium discoideum is a member of the ras-gene superfamily
      of low molecular weight GTPase proteins. The rap1 gene is expressed both during
      growth and development in D. discoideum. To examine the action of the Rap1
      protein in D. discoideum, the rap1 cDNA was expressed under the control of the
      inducible discoidin promoter. Treatment with conditioned media, which induces the
      discoidin promoter, increased Rap1 protein levels in vegetative cells
      approximately six fold. Overexpression of the Rap1 protein correlated with the
      appearance of morphologically aberrant vegetative amoebae: cells were extensively
      spread and flattened. The distribution of F-actin was altered in these cells,
      with an increase in actin staining around the cell periphery. Induction of the
      discoidin promoter by starvation in the rap1 transformants also resulted in
      spread flat cells. When starved D. discoideum amoebae are refed with HL5 media,
      the cells rapidly respond by rounding up. By contrast, the rap1 transformant
      cells showed a pronounced delay in rounding up. Rapid tyrosine phosphorylation of
      a p45 protein occurred in both control cells and the rap1 transformant upon
      refeeding, implying that the signal transduction pathway leading to tyrosine
      phosphorylation remained functional in the rap1 transformant. We propose that the
      Rap1 protein functions in the regulation of cell morphology in D. discoideum.

PMID- 7507421
TI  - TFIIIA and DNA supercoiling: toward resolving a controversy.
AB  - DNA supercoiling in eukaryotes is mediated by the process of chromatin assembly.
      This process couples the binding and wrapping of DNA around nucleosomal core
      particles and the enzymatic activity of DNA topoisomerase(s). Kmiec and Worcel
      (1985) reported that the binding of an RNA polymerase III transcription factor
      (TFIIIA) could accelerate DNA supercoiling catalysed by a Xenopus laevis cell
      free extract. Although the reaction was repeatedly reproduced in the parent
      laboratory by numerous workers, another laboratory, interested in the molecular
      biology of TFIIIA, failed to reproduce TFIIIA-mediated supercoiling or gyration.
      In this review, an attempt is made to transcend personal beliefs and describe the
      experimental approaches used to clarify this issue. The original variability lay
      in the amount of endogenous RNA within the cell free extract and the
      concentrations of MgCl2 used to conduct the experiments.

PMID- 7507420
TI  - Recent advances in nuclear matrix function.
AB  - The nuclear matrix in eukaryotes is a non-histone proteinaceous nucleoskeleton
      structure having attachment sites for DNA loops during DNA replication. The
      nuclear matrix has been implicated in transcription, regulation of gene
      expression, primary transcription processing and provides a mooring for certain
      hormone receptors. Moreover, the nuclear matrix protein has linkages to
      intermediate filaments of the cytoskeleton. This review presents recent advances
      concerning the involvement of the nuclear matrix in DNA replication, relaxation
      of the superhelical strain in DNA, processing of hnRNA and snRNP, and RNA
      transport.

PMID- 7507422
TI  - Frequency analysis and duration of motor unit potentials: reliability and
      diagnostic usefulness.
AB  - We studied the correlation, reliability and diagnostic usefulness of different
      time and frequency parameters of motor unit potentials (MUPs). Most frequency
      parameters were redundant because of high correlation with conventional MUP
      parameters. Variable selection algorithms for discriminant analysis indicated
      that center frequency (CENTFR) and spike duration (SPD) improved the
      discrimination between MUPs from normal, myopathic and neuropathic muscles. This
      was corroborated by univariate statistical tests comparing mean MUP duration
      (DUR), mean CENTFR and mean SPD of pathological muscles with those of normal
      muscles. One-sided tests for increased mean SPD improved the sensitivity for
      neurogenic changes and one-sided tests for reduced mean CENTFR improved the
      sensitivity for myopathic changes. The rate of false positive results did not
      increase by these additional tests. The retest reliability of CENTFR was superior
      to that of DUR. CENTFR and SPD are recommendable new parameters for quantitative
      MUP analysis based either on multi- or univariate statistics.

PMID- 7507419
TI  - Characterization of a human corneal metalloproteinase inhibitor (TIMP-1).
AB  - The gradual corneal thinning seen in keratoconus may be due to altered
      degradation of the corneal extracellular matrix. Studies have shown that human
      keratocytes produce matrix metalloproteinase-2 (MMP-2) and two proteins (28 kDa
      and 21 kDa) that are capable of inhibiting the activity of MMP-2. In the present
      study, the 28 kDa inhibitor from keratoconus keratocyte cultures has been
      characterized as it may be important to the elevated MMP-2 activity seen in these
      cultures. Biochemical analyses indicated that this keratoconus corneal inhibitor
      was similar to TIMP-1 from other sources. Oligonucleotides to the reported
      sequence of human tumor cell TIMP-1 were used for reverse-transcriptase PCR to
      generate a 700 bp clone of the 28 kDa inhibitor from keratoconus keratocyte
      cytoplasmic RNA. Sequence analysis verified that the clone was nearly identical
      to the reported human TIMP-1 with a single base substitution that did not affect
      the predicted amino acid sequence. In addition, protein translated from the clone
      corresponded to the expected size. This data suggests that the elevated levels of
      gelatinolytic activity in these keratoconus keratocyte cultures is not due to a
      primary alteration of the TIMP-1 molecule. Protein expression studies of the TIMP
      1 clone are currently underway.

PMID- 7507423
TI  - Comparison of two techniques to measure the motor nerve conduction velocity
      distribution.
AB  - Hopf's technique to measure the distribution of motor nerve conduction velocities
      (DMCV) has been compared with the technique introduced by Ingram et al. in the
      peroneal nerve of 28 healthy subjects 41.2 (S.D. 8.4) years. Twenty subjects were
      examined twice. Both techniques yielded an equal DMCV and equally reproducible
      results. Group mean velocities for the slowest examined (MNCV95) motor nerve
      fibres were 39.0 m/sec (S.D. 3.3) for Ingram's technique and 38.6 (S.D. 3.6) for
      Hopf's technique. The conventional MNCV was always slower than the velocity of
      the 5% fastest fibres estimated from the DMCV. Ingram's technique may have a
      number of merits which may have been obscured by measurement in the peroneal
      nerve, which may be of advantage in shorter nerve segments or faster nerve
      fibres. On the basis of our data in the peroneal nerve of healthy subjects no
      preference can be given for either of the techniques.

PMID- 7507424
TI  - Fasciculation-myokymic activity and prolonged nerve conduction block. A
      physiopathological relationship in radiation-induced brachial plexopathy.
AB  - Fourteen radiation-induced brachial plexus neuropathies in 12 patients suffering
      from cancer were studied. Neurophysiological evaluation showed a diffuse
      neurogenic lesion with muscular denervation signs associated with motor and
      sensory nerve conduction impairment of axonal type in the distal segments of the
      arm. Somatosensory evoked potentials were frequently abnormal, with absence of N9
      in 9 out of the 10 extremities explored. The most characteristic findings were,
      however, the presence of fasciculation potentials--single and grouped--and
      myokymic discharges in 78.5% of cases (11 out of 14 plexuses), and a motor nerve
      conduction block on proximal stimulation, at the supraclavicular as well as
      cervical spine levels, in all of the cases. Both phenomena showed a high
      correlation when analyzed in the same neuromuscular territory. The 5 muscles with
      no voluntary activity and complete--or nearly complete--motor nerve conduction
      block were the ones with the most intense ectopic activities. The conduction
      blocks were present after long periods of illness in all cases and, in 2 of the
      cases, they persisted in successive explorations at intervals of 9 months and 2
      years respectively. These data would support a probable cause-effect relationship
      between a persistent and prolonged motor nerve conduction block and the presence
      of fasciculation-myokymic type activities. One could even postulate that the
      infrequent neuropathies, in which both findings have been described as relevant
      features, have a similar physiopathological mechanism.

PMID- 7507425
TI  - Sensory nerve findings by tactile stimulation of median and ulnar nerves in
      healthy subjects of different ages.
AB  - We studied orthodromic sensory conduction velocity along the distal and proximal
      segments of the median and ulnar nerves by tactile stimulation of the distal
      phalanx of the 3rd and 5th digits in 44 healthy subjects divided into 2 age
      groups: from 16 to 35 years and from 63 to 81 years. In the same nerves, we used
      selective electrical stimulation of the corresponding digital nerves to obtain
      sensory potentials. In both groups, responses to tactile stimuli had a longer
      latency and smaller amplitude than those to electrical stimulation, and they were
      distributed in a series of 6-7 main deflections, apparently regardless of whether
      the recording site was distal or proximal. Moreover, irrespective of the nerve
      and of subject age, conduction velocity along both the digit-wrist and the wrist
      elbow nerve segments was significantly slower with tactile stimuli than with
      electrical stimuli. However, independently of the stimulus used, conduction
      velocity along the proximal nerve segment was significantly faster than that
      measured along the digit-wrist nerve segment. In both the median and ulnar
      nerves, maximum potential amplitude, cumulative area and conduction velocity were
      significantly reduced in the older age group. This finding could reflect the
      smaller number of Meissner's corpuscles in older subjects, and the loss of large
      nerve fibres in individuals over 60.

PMID- 7507426
TI  - Increased dependence upon visual information of movement performance during visuo
      motor tracking in cerebellar disorders.
AB  - The effect of temporarily suppressing the visual display of either the target
      (desired) trajectory or the actual movement trajectory upon the accuracy of visuo
      motor tracking was studied in 6 patients with cerebellar syndromes and 6 healthy
      subjects. Subjects made extension and flexion movements of the wrist to
      superimpose a cursor displaying their actual movement (movement cursor) upon one
      indicating the target (target cursor) on a VDU screen. The target trajectory
      consisted of a sawtooth pattern of slow (4 deg/sec) ramp extension and
      instantaneous flexion return phases. Following practice, the tracking of
      cerebellar patients was significantly less accurate than that of healthy subjects
      for each phase (P = 0.02). Temporary suppression of the movement cursor during
      both the mid-section of the ramp phase (P = 0.05) and around the reversal phase
      (P = 0.04) caused a significant increase in tracking errors in the patients
      whereas suppression of the target cursor did not alter their performance.
      Suppression of neither cursor altered the tracking accuracy of healthy subjects
      during the ramp extensions whilst suppression of either caused reduced (P = 0.02)
      performance for the reversal phase. We interpret the increased dependence of
      patients upon visual information of their movements during slow trajectories as
      indicating an impairment of proprioceptive guidance.

PMID- 7507427
TI  - Abnormal EPSPs evoked by magnetic brain stimulation in hand muscle motoneurons of
      patients with amyotrophic lateral sclerosis.
AB  - Using cross-correlation between magnetic brain stimulation and discharges of a
      motoneuron made active by a slight voluntary contraction, an indirect estimate of
      the EPSP evoked by magnetic brain stimulation in single hand muscle motoneurons
      was obtained in patients with amyotrophic lateral sclerosis (ALS) and normal
      controls. In total, 60 motoneurons of 3 normal subjects and 70 motoneurons of 7
      patients with ALS were investigated. All motoneurons of normal subjects responded
      to the magnetic brain stimulus with a short-latency EPSP with a rise time between
      1 and 5 msec. In contrast, only 67% of the motoneurons from ALS patients
      responded with an EPSP while the remaining 33% exhibited a clear short-latency
      inhibition in response to the brain stimulus. For those units of ALS patients
      showing an EPSP, both latency and EPSP amplitude were indistinguishable from
      those of normal subjects. The EPSP rise time, however, was massively prolonged in
      some units (up to 18 msec). These results provide a physiological basis for the
      interpretation of surface EMG responses in patients with ALS.

PMID- 7507428
TI  - Variability of motor potentials evoked by transcranial magnetic stimulation.
AB  - We studied the effect of stimulus intensity, coil size, mental alertness and
      prestimulus muscle contraction on the variability of motor evoked potentials
      (MEPs) produced by magnetic cortical stimulation (MCS). In 5 healthy subjects we
      delivered MCS either with a circular coil centered at the vertex or a figure-8
      coil centered over the motor cortex hand area, recording from first dorsal
      interosseous. With the subject at rest or exerting 5% maximum voluntary
      contraction, 30 consecutive stimuli were given at 4 stimulus intensities (SIs) in
      10% increments above resting motor threshold. Concurrent mental arithmetic
      constituted mental alertness. Spectral analysis was performed on data from 300
      consecutive stimuli. The variability of MEP response size was inversely related
      to stimulus intensity, prestimulus voluntary muscle contraction, the recruitment
      of motoneurons and the size of the field generated by the magnetic coil. The MEP
      variability was larger than and not correlated with the variability of the H
      reflex. Fast Fourier transformation and cross-correlation analysis did not
      identify a consistent dominant frequency, suggesting that the variability in MEP
      size is essentially random. We suggest that the variability in MEP response is
      caused by constant, rapid, spontaneous fluctuations in corticospinal and
      segmental motoneuron excitability levels. Any maneuver that raises this level or
      increases the probability of motoneuron firing will decrease MEP variability.

PMID- 7507429
TI  - Topography of the inhibitory and excitatory responses to transcranial magnetic
      stimulation in a hand muscle.
AB  - We studied the excitatory motor evoked potentials (MEPs) and the inhibitory
      (silent period) responses to focal transcranial magnetic stimulation (TMS) in the
      abductor pollicis brevis (APB) of 5 normal subjects to learn whether the scalp
      topography of the two responses differed. At the scalp location where stimulation
      produced the highest-amplitude MEP in the voluntarily activated APB, stimulus
      intensities below the MEP threshold produced silent periods with little or no
      preceding facilitation. The silent periods had a mean duration of 26.8 +/- 6.8
      msec and a mean onset latency of 27.6 +/- 3.6 msec, which was 7.2 +/- 2.3 msec
      longer than the latency of MEPs produced in the APB by higher stimulus
      intensities. A period of excitation, with an onset latency of 50-80 msec, often
      followed the silent period. On averaged trials, a stimulus intensity just above
      the threshold of the MEP at its optimal position produced MEPs followed by silent
      periods at a cluster of scalp locations 1 cm apart on the central scalp (medial
      area) and silent periods with very slight or no preceding facilitation in 3-9
      locations lateral to the MEP area (lateral area). This finding was confirmed in 3
      subjects with maps constructed from statistical analysis of multiple trials.
      These maps also showed that MEPs produced from the medial area occurred 4-6 msec
      earlier than those produced from the lateral area. The integral of the silent
      period tended to be larger in the lateral area. The motor representation of APB,
      as defined by TMS, is not homogeneous but rather contains at least two components
      that differ physiologically and topographically.

PMID- 7507430
TI  - Central motor conduction time in neurological decompression illness.

PMID- 7507431
TI  - Posterior tibial and sural nerve somatosensory evoked potentials: a study in
      spastic paraparesis and spinal cord lesions.
AB  - In two groups of patients posterior tibial nerve (PTN) and sural nerve (SN)
      somatosensory evoked potentials (SEPs) were compared to each other and related to
      classified neurological signs. Group A consisted of 7 patients with hereditary
      spastic paraparesis (HSP) and 8 with primary lateral sclerosis (PLS), with solely
      or primarily motor deficits. Group B consisted of 12 patients with different
      spinal cord diseases causing variable mixed sensory and motor impairments. Normal
      values were derived from 39 controls. A clear trend towards more frequently
      prolonged PTN SEP than SN SEP latencies was found in both groups and appears to
      make PTN SEPs more useful for clinical application than SN SEPs. No significant
      differences were found in SEP abnormalities when the two patient groups were
      compared to each other. No relationships were found between SEP abnormalities and
      spasticity, weakness or any single sensory modality, making the two SEPs
      questionable as a quantitative test for neurological deficits in our patients.

PMID- 7507432
TI  - Sudomotor skin responses following nerve and brain stimulation.
AB  - A comparative evaluation of sudomotor innervation to the limbs and perineum was
      made using electrical stimulation of the median nerve at the wrist and
      transcranial magnetic stimulation of the brain. Sympathetic skin responses (SSRs)
      were recorded from the palms (SSR-1), the soles (SSR-2) and the perineum (SSR-3).
      Normative data in 25 volunteers showed the following latencies in seconds:
      [table: see text].

PMID- 7507433
TI  - Sudomotor skin responses to brain stimulation do not depend on nerve sensory
      fiber functionality.
AB  - Evaluation of sudomotor innervation to the limbs was performed via electrical
      stimulation of the median nerve at the wrist and transcranial magnetic
      stimulation of the brain. Sympathetic skin responses (SSRs) from the palms and
      the soles were recorded in a patient suffering from a form of predominantly
      sensory neuropathy. Motor responses to nerve stimulation were present, even if
      with slower than normal conduction velocity. However, median, ulnar and sural
      nerve sensory potentials were absent. SSRs to median nerve stimulation at the
      wrist were missing on palms and soles. By contrast, during brain stimulation of
      the hand motor area with magnetic impulses, SSRs were reliably identifiable at
      all recording sites. It is hypothesized that SSRs to mixed nerve stimulation need
      normal functionality of afferent fibers, while those to brain stimulation can be
      elicited without any sensory information from the limbs.

PMID- 7507434
TI  - Muscle innervation.

PMID- 7507435
TI  - Isoforms of nitric oxide synthase: functions in the cardiovascular system.
AB  - Various cell types, including endothelial cells, can synthesize nitric oxide
      (NO). Three different isoforms of NO synthase have been characterized, purified
      and cloned. Isozyme I is present in neuronal cells of the brain (where NO may
      mediate synaptic plasticity), in peripheral non-adrenergic non-cholinergic (NANC)
      neurons (where NO acts as an atypical neurotransmitter relaxing vascular and non
      vascular smooth muscle), and in various specialized epithelial cells. Macrophages
      can be induced with bacterial endotoxin and/or cytokines to express isozyme II.
      The high concentrations of NO produced by this isoform have cytostatic effects on
      parasitic microorganisms and tumour cells. A similar isozyme can be induced in
      the vascular wall (presumably in smooth muscle cells) in sepsis and during
      cytokine therapy. The large amounts of NO produced by this enzyme contribute to
      the symptoms of septic shock, such as vasodilatation and microvascular
      endothelial damage. Endothelial cells contain isoform III of NO synthase which
      seems to be unique for this cell type. Endothelium-derived NO is a
      physiologically significant vasodilator and inhibitor of platelet aggregation and
      adhesion. In addition, vascular NO can prevent leukocyte adhesion to the
      endothelium by interfering with the adhesion molecule CD11/CD18, and NO has also
      been shown to inhibit the proliferation of vascular smooth muscle cells. Hence,
      NO represents a protective factor against vascular damage and probably
      atherogenesis.

PMID- 7507436
TI  - Preserved endothelial function in the spastic segment of the human epicardial
      coronary artery in patients with variant angina--role of substance P in
      evaluating endothelial function.
AB  - This study aimed to determine whether or not endothelium-dependent vasodilation
      is preserved in spastic segments of human epicardial coronary arteries. Segmental
      responses of coronary arteries to substance P were examined in 30 patients with
      variant angina and in 10 patients with atypical chest pain using a quantitative
      angiographic technique. Coronary diameter at the basal state was matched between
      spastic and non-spastic segments in patients with variant angina, normal coronary
      arteries and with atypical chest pain (2.3 +/- 0.2 mm, 2.3 +/- 0.4 mm, 2.4 +/-
      0.3 mm, respectively). In segments where vasospasm was induced by ergonovine
      and/or acetylcholine, changes in diameter in response to substance P did not
      differ from those in non-spastic segments; maximal dilation averaged 27.1 +/-
      9.5% in the spastic segments and 24.4 +/- 9.6% in the non-spastic segments
      (expressed as a percent increase over the value before drug administration). It
      would appear that the potential of the endothelium to release endothelium
      dependent relaxant factor (EDRF) and the vasodilator response to EDRF are
      preserved, even in spastic segments.

PMID- 7507438
TI  - Novel actions of methylene blue.
AB  - Methylene blue has been frequently used as an inhibitor of soluble guanylyl
      cyclase. We found that endothelium-dependent relaxations of isolated blood
      vessels were considerably more sensitive to inhibition by methylene blue than
      relaxation induced by direct activators of soluble guanylyl cyclase. Similar data
      were obtained in the presence of superoxide dismutase, indicating that the
      diverse potencies of methylene blue were not due to superoxide-induced
      inactivation of nitric oxide (NO). Subsequent experiments revealed that methylene
      blue is an inhibitor of purified NO synthase. Conversion of L-arginine to L
      citrulline was inhibited by the dye in a concentration-dependent fashion with
      half-maximal effects observed at 5.3 microM and 9.2 microM in the absence and
      presence of superoxide dismutase, respectively. Purified soluble guanylyl
      cyclase, however, was far less sensitive to methylene blue. When the enzyme was
      maximally stimulated with S-nitroso-glutathione, cyclic guanosine monophosphate,
      (cGMP) formation was reduced by 50% at approximately 60 microM methylene blue; 1
      mM produced maximal inhibitions of about 70%. Our data indicate that methylene
      blue is only a poor inhibitor of soluble guanylyl cyclase. The dye seems to act
      primarily via inhibition of NO synthase, with enzyme-bound heme being a possible
      target in its inhibitory action.

PMID- 7507437
TI  - Role of the L-arginine-nitric oxide pathway in vascular smooth muscle.
AB  - This brief overview discusses the ability of mediators associated with vascular
      injury, such as interleukin-1 beta and tumour necrosis factor alpha, to activate
      vascular smooth muscle cells to produce nitric oxide or a related donor of nitric
      oxide. The cytokines cause the synthesis of nitric oxide synthase(s), which
      catalyzes the conversion of L-arginine to nitric oxide and L-citrulline. The
      production of nitric oxide can be modulated by factors produced by vascular cells
      and formed elements of the blood (e.g. platelet-derived growth factor,
      transforming growth factor beta), but also by those generated at sites of
      vascular injury from inactive precursors circulating in the blood (e.g. thrombin,
      plasmin). The production of nitric oxide by vascular smooth muscle cells may
      contribute to the homeostasis of blood vessels at sites of injury. In particular,
      nitric oxide may prevent the local development of vasospasms, unwanted
      proliferation of smooth muscle cells, and also help to control coagulation and
      the formation of the thrombus.

PMID- 7507439
TI  - The effect of prostaglandins and thromboxane A2 on coronary vessel tone-
      mechanisms of action and therapeutic implications.
AB  - Prostaglandins (PGI2, PGE2, PGF2 alpha) and thromboxane (TX) A2 are vasoactive,
      cell membrane-derived lipid mediators that are formed in response to stimulation
      of vascular smooth muscle cells by a variety of chemical agonists. Different
      receptor subtypes mediate the contractile and relaxing effects of prostaglandins
      and TXA2 on coronary vascular smooth muscle: a high-affinity (kD: > or = 1 nM)
      PGH2/TXA2 receptor mediates the contractile actions of TXA2; a low-affinity (kD
      100-200 nM) receptor mediates the contractile actions of other prostaglandins
      ('primary prostaglandin receptor') and a PGI2 receptor (kD > or = 20 nM) mediates
      vessel relaxation. These receptors are coupled to intracellular signal
      transduction pathways via different G-proteins and modify muscle tone by control
      of cytosolic Cai++. Ca(++)- and ATP-dependent K-channels are regulated by PGI2
      (opening) and TXA2 (closure) and are involved in the setting of coronary smooth
      muscle tone. There is experimental and clinical evidence for enhanced local TXA2
      levels, an increased number of platelet TXA2 receptors and a reduced number of
      PGI2 receptors in acute myocardial infarction. There is also experimental
      evidence for increased synthesis of PGF2 alpha-receptors in vascular smooth
      muscle that may mediate smooth muscle proliferation. The interference of both
      TXA2 and PGI2 with K(+)-channels in coronary arteries may have important
      implications for coronary vasospasm and ischaemia-related cardiac hypoperfusion.

PMID- 7507440
TI  - Structural requirements for altering the L-tryptophan metabolism in mice by
      organophosphorous and methylcarbamate insecticides.
AB  - This study defined structural requirements for organophosphorous and
      methylcarbamate insecticides for altering the L-kynurenine pathway of L
      tryptophan metabolism in mice. Kynurenine formamidase inhibition by
      organophosphorous acid triesters and methylcarbamates is the proposed primary
      event resulting in increase in xanthurenic acid urinary excretion and plasma L
      kynurenine. Alteration of the L-kynurenine pathway occurred with compounds that
      inhibited liver kynurenine formamidase by more than 80%. Pyrimidinyl
      phosphorothioates followed by crotonamide phosphates were the most potent
      compounds that changed L-tryptophan metabolism, i.e., pirimiphos-ethyl (20 mg/kg)
      inhibited liver kynurenine formamidase by 99%, and increased xanthurenic acid
      urinary excretion and plasma L-kynurenine by 576 +/- 195 and 330 +/- 44%,
      respectively. Replacement of sulphur by oxygen in the phosphorothioate diazinon
      reduced in vivo liver kynurenine formamidase inhibition. Consequently,
      xanthurenic acid urinary excretion and plasma L-kynurenine were not elevated.
      Atropine, cycloheximide, 2-PAM and phenylmethylsulfonyl fluoride did not
      alleviate diazinon-altered L-tryptophan metabolism. Because of the potential of
      the majority of organophosphorous acid triesters and methylcarbamates to inhibit
      kynurenine formamidase, this novel noncholinergic mechanism warrants
      consideration in assessment of organophosphorous and methylcarbamate toxicity in
      occupational and accidental exposures.

PMID- 7507442
TI  - Induction of phagocytic activity of M1 cells by an inhibitor of vacuolar H+
      ATPase, bafilomycin A1.
AB  - Bafilomycin A1, a selective inhibitor of vacuolar H+-ATPase, time- and dose
      dependently induced the differentiation of M1 cells, a murine myeloid leukemic
      cell line, into macrophage-like cells as revealed by the phagocytosis of
      polystyrene latex particles. This differentiation was inhibited not only by
      actinomycin D and cycloheximide but also by ST-638 (an inhibitor of tyrosine
      kinase). However, it was affected neither by K-252a (an inhibitor of C-kinase)
      nor by H-89 (an inhibitor of A-kinase), in contrast to the M1 cell
      differentiation induced by leukemia inhibitory factor (LIF). Okadaic acid
      inhibited both the bafilomycin A1-induced and LIF-induced differentiation of M1
      cells.

PMID- 7507441
TI  - Steady-state kinetic studies with the polysulfonate U-9843, an HIV reverse
      transcriptase inhibitor.
AB  - The tetramer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT*
      and possesses excellent antiviral activity at nontoxic doses in HIV-1 infected
      lymphocytes grown in tissue culture. Kinetic studies of the HIV-1 RT-catalyzed
      RNA-directed DNA polymerase activity were carried out in order to determine if
      the inhibitor interacts with the template primer or the deoxyribonucleotide
      triphosphate (dNTP) binding sites of the polymerase. Michaelis-Menten kinetics,
      which are based on the establishment of a rapid equilibrium between the enzyme
      and its substrates, proved inadequate for the analysis of the experimental data.
      The data were thus analyzed using steady-state Briggs-Haldane kinetics assuming
      that the template: primer binds to the enzyme first, followed by the binding of
      the dNTP and that the polymerase is a processive enzyme. Based on these
      assumptions, a velocity equation was derived which allows the calculation of all
      the specific forward and backward rate constants for the reactions occurring
      between the enzyme, its substrates and the inhibitor. The calculated rate
      constants are in agreement with this model and the results indicated that U-9843
      acts as a noncompetitive inhibitor with respect to both the template:primer and
      dNTP binding sites. Hence, U-9843 exhibits the same binding affinity for the free
      enzyme as for the enzyme-substrate complexes and must inhibit the RT polymerase
      by interacting with a site distinct from the substrate binding sites. Thus, U
      9843 appears to impair an event occurring after the formation of the enzyme
      substrate complexes, which involves either an event leading up to the formation
      of the phosphoester bond, the formation of the ester bond itself or translocation
      of the enzyme relative to its template:primer following the formation of the
      ester bond.

PMID- 7507443
TI  - Ion permeability induced in artificial membranes by the ATP/ADP antiporter.
AB  - The hypothesis on the additional function of the ATP/ADP antiporter (ANT) as
      uncoupling protein has been tested in proteoliposomes and planar bilayer
      phospholipid membranes (BLM). It is found that dissipation of the light-induced
      delta pH in the dark is very much faster in ANT-bacteriorhodopsin proteoliposomes
      than in proteoliposomes containing bacteriorhodopsin as the only protein.
      Mersalyl treatment of ANT-bacteriorhodopsin proteoliposomes causes further
      increase in the delta pH dissipation rate due to formation of a high conductance
      pore. The properties of this pore are studied on ANT incorporated to BLM. They
      proved to be similar to those of so-called multiple conductance channel or
      permeability transition pore of inner mitochondrial membrane. The conductance of
      the single channel is as high as 2.2 nS. The channel fails to discriminate
      between K+, Na+, H+ and Cl-. Thus the obtained data are consistent with the
      assumption that native and modified ANT might function as an H(+)-specific
      conductor and as a permeability transition pore, respectively.

PMID- 7507444
TI  - Growth factors and growth modulators in human uterine endometrium: their
      potential relevance to reproductive medicine.
AB  - OBJECTIVE: To provide an up-to-date, comprehensive review on the presence and
      regulation of growth factors (GFs), GF receptors, and GF regulatory proteins in
      human endometrium in an effort to understand the potential roles of these
      proteins in endometrial cell mitosis and differentiation and in endometrial
      trophoblast interactions. DESIGN: Relevant studies were identified through a
      computerized bibliographic search (MEDLINE; BRS Information Technologies, a
      division of Maxwell Online, Inc., McLean, VA) and through manual scanning of
      recent relevant journals. RESULTS: Several GFs, their receptors, and regulatory
      proteins have been identified in endometrium, and cellular localization and
      steroid-dependence of these proteins as well as action of several growth
      modulators on endometrial cell function have been studied. Epidermal growth
      factor, transforming growth factor (TGF)-alpha, platelet-derived growth factor,
      insulin-like growth factors (IGFs) and their binding proteins, fibroblast growth
      factor (FGF), TGF-beta, colony-stimulating factor (CSF)-1, and interferon-gamma
      regulate mitosis of endometrial cellular components in vitro. Endothelin-1 may
      participate in vasoconstriction and FGF may participate in angiogenesis in this
      tissue in vivo. Interleukins-1 and -6 are believed to be involved in endometrial
      T-cell activation, and TGF-beta, CSF-1, the interleukins, and the IGFs likely
      mediate endometrial-trophoblast interactions. The role of tumor necrosis factor
      in endometrium remains uncertain. CONCLUSIONS: Current evidence supports the
      thesis that GFs play a central role in cyclic mitosis and differentiation of
      endometrial cellular components, recruitment of macrophages in decidualizing
      endometrium, endometrial-trophoblast interactions, early pregnancy maintenance,
      tissue shedding in the absence of implantation, and endometrial functionalis
      regeneration.

PMID- 7507446
TI  - Gamma-tubulin is asymmetrically distributed in the cortex of Xenopus oocytes.
AB  - Stage VI Xenopus oocytes contain an extensive network of cytoplasmic microtubules
      (MTs), with no evidence of a functional centrosome. Recently, Stearns et al.
      (1991) demonstrated that Xenopus eggs contain a substantial pool of the
      centrosomal protein gamma-tubulin (gamma-Tb). For this report, I have used
      confocal immunofluorescence microscopy to examine the distribution of gamma-Tb
      during the later stages of oogenesis in Xenopus laevis. gamma-Tb was apparent
      surrounding the germinal vesicle (GV) of stage VI oocytes, consistent with
      previous results suggesting that the GV serves as an microtubule organizing
      center in later oogenesis. Surprisingly, gamma-Tb was also concentrated in the
      cortex of stage VI oocytes, and the distribution of cortical gamma-Tb was
      polarized along the animal-vegetal (A-V) axis. In the vegetal cortex, gamma-Tb
      was observed in brightly stained foci, often organized into short linear arrays.
      In the animal hemisphere, gamma-Tb was more evenly distributed as small cortical
      foci. Dual immunofluorescence microscopy revealed that gamma-Tb in the vegetal
      hemisphere was associated with MTs in the cortical cytoplasm. The distribution of
      gamma-Tb was not significantly affected by either cold or nocodazole, but was
      partially disrupted by cytochalasin B. gamma-Tb thus may serve as a link between
      the oocyte MT network and cortical actin. Finally, polarization of the
      distribution of cortical gamma-Tb temporally coincides with formation of the A-V
      axis and polarization of the oocyte MT cytoskeleton during stage IV of oogenesis.
      These observations raise a number of questions regarding the organization and
      orientation of MTs during Xenopus oogenesis and the role of gamma-Tb in the
      polarization of the oocyte cytoskeleton during A-V axis formation.

PMID- 7507445
TI  - Increase of lymphocytes expressing Fc-receptor class III (CD16) by exposure to
      human seminal plasma.
AB  - OBJECTIVE: To characterize conditions for the seminal plasma-induced increase of
      lymphocytes that express immunoglobulin G-Fc receptor class III (Fc gamma RIII).
      DESIGN: Peripheral blood lymphocytes were incubated in diluted seminal plasma or
      control media. Cells expressing Fc gamma RIII were quantified by using flow
      cytometry and fluorochrome-labeled monoclonal antibodies specific for Fc gamma
      RIII. The influence of incubation time, temperature, and seminal plasma
      concentration was investigated. Physical properties of the active seminal plasma
      substance were characterized by studying effects of dialysis and
      ultracentrifugation. The origin of the active seminal plasma substance was
      investigated by studying activity of autopsy materials from male accessory
      glands. Identity of cells that are influenced by seminal plasma activity was
      investigated by using two-color flow cytometry with monoclonal antibodies
      specific for Fc gamma RIII and different phenotypic markers of leukocytes.
      RESULTS: Incubation of lymphocytes in seminal plasma significantly increased
      percentages of cells expressing Fc gamma RIII. Maximal increases were observed
      after seminal plasma incubation at 37 degrees C for 90 to 120 minutes and
      increases were significantly correlated with seminal plasma concentration.
      Seminal plasma activity was not altered by ultracentrifugation (100,000 x g for
      30 minutes) but completely removed by dialysis (12,000 to 14,000 pore size). Fc
      gamma RIII-positive lymphocytes markedly increased after incubation in prostatic
      but not in seminal vesicle secretions. Two-color flow cytometry showed that
      increases of Fc gamma RIII-expressing cells occurred within the subset of CD56
      positive natural killer (NK) cells. CONCLUSIONS: Dialyzable compounds of
      prostatic origin induce significant increases of NK cells expressing Fc gamma
      RIII. These findings might reflect a novel regulatory mechanism acting on CD56
      positive cells within the female reproductive tract after insemination.

PMID- 7507447
TI  - The ligand of the c-kit receptor promotes oocyte growth.
AB  - Both genetic and descriptive studies have implicated the c-kit receptor and its
      ligand, KL, in the process of oocyte growth in the postnatal mouse ovary. In
      order to test the hypothesis that KL is an oocyte growth factor, we used an
      oocyte culture system to study its effects in vitro. Initial experiments
      established that both ovarian c-kit and KL are biologically active. An immune
      complex kinase assay demonstrated that ovarian c-kit, found primarily on oocytes,
      has autophosphorylation activity, and a bone marrow-derived mast cell coculture
      assay indicated that granulosa cells produce functional KL. The addition of 10
      ng/ml KL to growing follicles cultured in collagen gels resulted in a 67%
      increase in the rate of oocyte growth, and a doubling of the rate was achieved at
      around 50 ng/ml. ACK2, a monoclonal antibody against c-kit, severely inhibited
      the growth of late fetal and neonatal oocytes in coculture with ovarian cells and
      had less effect on growing oocytes cultured in follicles from 10- to 11-day-old
      mice. Genistein, an inhibitor of tyrosine kinases, including c-kit, blocked
      oocyte growth and disrupted follicle morphology. In initial studies on the
      regulation of KL production in granulosa cells, we found that both dibutyryl
      cyclic AMP and growing oocytes were able to induce increased KL mRNA accumulation
      in granulosa cell monolayers as assessed by Northern analysis. These studies
      demonstrate that c-kit and KL are required for maintenance of oocyte growth in
      vitro.

PMID- 7507448
TI  - Acquisition of meiotic competence by denuded mouse oocytes: participation of
      somatic-cell product(s) and cAMP.
AB  - In contrast to fully grown oocytes, growing mouse oocytes are not capable of
      undergoing germinal vesicle breakdown (GVB) when released from the follicle
      unless they are first cultured in somatic-cell-conditioned medium. The first
      objective of this study was to assess the mechanisms by which oocytes in vitro
      acquire the ability to resume meiosis in conditioned medium. Whereas most of the
      denuded oocytes that were initially incompetent of undergoing GVD underwent GVB
      within 4 days of culture in fibroblast-conditioned medium, oocytes cultured in
      control medium remained in the GV stage although their viability was sustained as
      judged by morphological appearance and quantitative and qualitative patterns of
      protein synthesis. This suggested that the effect of somatic-cell-conditioned
      medium is inductive rather than simply permissive. When GVB-incompetent oocytes
      were first incubated in control medium for 1-3 days, a larger percentage
      underwent GVB following exposure to the conditioned medium or okadaic acid. It
      was therefore concluded that some aspects of the oocytes' developmental program
      for the acquisition of GVB competence are oocyte-autonomous but external factors
      provided by the surrounding somatic cells are probably require for oocytes to
      become fully GVB-competent. The effect of cAMP on acquisition of GVB competence
      by growing oocytes was also studied. Dibutyryl cAMP dose-dependently promoted the
      acquisition of GVB competence by initially GVB-incompetent oocytes. Forskolin, an
      adenylate cyclase activator, acted in similar way and its effect was potentiated
      by hypoxanthine, a naturally occurring cAMP-phosphodiesterase inhibitor. Thus
      cAMP, in addition to maintaining meiotic arrest in GVB-competent oocytes, also
      participates in the acquisition of GVB competence by growing oocytes.

PMID- 7507450
TI  - Treatment of "obstructive" pain by endoscopic drainage in patients with
      pancreatic head carcinoma.
AB  - Obstruction of the main pancreatic duct with secondary upstream ductal
      hypertension is one cause of pain in patients with pancreatic cancer. Pancreatic
      endoscopic stenting and decompression of the pancreatic duct have been effective
      in the treatment of pain secondary to chronic calcifying pancreatitis and in one
      case of pancreatic cancer. We describe eight patients with unresectable cancer of
      the pancreatic head associated with upstream dilatation of the pancreatic duct
      and severe pancreatic "obstructive"-type pain (correlation with meals and pain
      radiation to the back) in which a pancreatic stent was inserted across the
      neoplastic stricture. No mortality was associated with the procedure. All
      patients but one were free of pain within 48 hours after endoscopic pancreatic
      stenting, and all discontinued narcotics. Mean survival time was 165.5 days
      (range, 26 to 575 days). Six patients were still without symptoms, whereas two
      had a painful relapse a few days before death. No clinical evidence of pancreatic
      clogged stent was observed during follow-up. Endoscopic pancreatic drainage is a
      safe and effective way of controlling cancer pain in selected cases and should be
      considered as a further therapeutic option in these patients.

PMID- 7507449
TI  - Tumor necrosis factor-alpha (TNF-alpha) stimulates proliferation of mouse
      primordial germ cells in culture.
AB  - Recent studies have shown that stem cell factor, leukemia inhibitory factor, and
      basic fibroblast growth factor increase proliferation and survival of the mouse
      primordial germ cells (PGCs) in culture. We now show that addition of tumor
      necrosis factor-alpha (TNF-alpha) to culture medium stimulates proliferation of
      PGCs without transforming them into embryonic stem cells and that its effect is
      specific for the PGCs at younger stages before and during their migration to
      gonads. A previously reported finding that TNF-alpha is expressed at these stages
      in mouse embryos suggests possible involvement of TNF-alpha in the proliferative
      regulation of the PGCs in the embryo.

PMID- 7507452
TI  - Mapping of the mAb73 epitope on Ad2 E1A proteins with random peptide libraries
      and deletion mutants.
AB  - mAb73, a monoclonal antibody against adenoviruses type 2 and 5 E1A, recognises an
      epitope within the C-terminal part of this protein. To identify the epitope we
      used random peptide libraries expressed on the surface of filamentous phages (Fd,
      M13). We found a consensus sequence homologous to the nuclear transport signal
      KRPRP at the C-terminus of Ad2 and Ad5 E1A. An E1A mutant deleted for these
      residues failed to be immunoprecipitated by mAb73, confirming that the nuclear
      transport signal of E1A is the epitope recognised by mAb73.

PMID- 7507451
TI  - Endoscopic India ink injection: a method for preparation, sterilization, and
      administration.

PMID- 7507453
TI  - Cloning, nucleotide sequence and structural analysis of the Clostridium
      acetobutylicum dnaJ gene.
AB  - The complete dnaJ gene of Clostridium acetobutylicum was isolated by chromosome
      walking using the previously cloned 5' end of the gene as a probe. Nucleotide
      sequencing of a positively reacting 2.2-kb HincII fragment, contained in the
      recombinant plasmid pKG4, revealed that the reading frame of the dnaJ gene of C.
      acetobutylicum consists of 1125 bp, encoding a protein of 374 amino acids with a
      calculated M(r) of 40376 and an isoelectric point of 9.54. The deduced amino acid
      sequence showed high similarity to the DnaJ proteins of other bacteria (e.g.
      Escherichia coli, Bacillus subtilis) as well as of an archaeon (Methanosarcina
      mazei) and to the corresponding proteins of eukaryotes (Saccharomyces cerevisiae,
      Homo sapiens). The areas of similarity included a conserved N-terminal domain of
      about 70 amino acids, a glycine-rich region of about 30 residues, and a central
      domain containing four repeats of a CXXCXGXG motif, whereas the C-terminal domain
      was less conserved. Northern (RNA) blot analysis indicated that dnaJ is induced
      by heat shock and that it is part of the dnaK operon of C. acetobutylicum. The 5'
      end (901 bp) of another gene (orfB), downstream of dnaJ and not heat-inducible,
      showed no significant similarity to other sequences available in EMBL and GenBank
      databases.

PMID- 7507454
TI  - An efficient positive selection procedure for the isolation of peroxisomal import
      and peroxisome assembly mutants of Saccharomyces cerevisiae.
AB  - To study peroxisome biogenesis, we developed a procedure to select for
      Saccharomyces cerevisiae mutants defective in peroxisomal protein import or
      peroxisome assembly. For this purpose, a chimeric gene was constructed encoding
      the bleomycin resistance protein linked to the peroxisomal protein luciferase. In
      wild-type cells this chimeric protein is imported into the peroxisome, which
      prevents the neutralizing interaction of the chimeric protein with its toxic
      phleomycin ligand. Peroxisomal import and peroxisome assembly mutants are unable
      to import this chimeric protein into their peroxisomes. This enables the
      bleomycin moiety of the chimeric protein to bind phleomycin, thereby preventing
      its toxicity. The selection is very efficient: upon mutagenesis, 84 (10%) of 800
      phleomycin resistant colonies tested were unable to grow on oleic acid. This rate
      could be increased to 25% using more stringent selection conditions. The
      selection procedure is very specific; all oleic acid non utilizing (onu) mutants
      tested were disturbed in peroxisomal import and/or peroxisome assembly. The pas
      (peroxisome assembly) mutants that have been used for complementation analysis
      represent 12 complementation groups including three novel ones, designated pas20,
      pas21 and pas22.

PMID- 7507455
TI  - Paramutation, an allelic interaction, is associated with a stable and heritable
      reduction of transcription of the maize b regulatory gene.
AB  - The b gene of maize encodes a transcriptional activator of anthocyanin pigment
      biosynthetic genes. Certain b alleles undergo paramutation: a unidirectional,
      heritable alteration of one allele caused by the presence of another allele. B-I
      (intensely pigmented plant) is always changed to B' (weakly pigmented plant) in
      the B'/B-I heterozygote, such that all progeny receive the B' allele. The "new"
      B', which was B-I in the previous generation, is weakly pigmented and fully
      capable of changing another B-I allele into B'. It was not previously known
      whether paramutation is associated with altered b expression, altered B protein
      function or both. Our results show that B' acts in trans to suppress the
      transcription of B-I, with transcription remaining low in subsequent generations,
      even when the original B' allele segregates away. The products of B-I and B' are
      equally capable of activating the transcription of their target genes, indicating
      they are functionally equivalent. Genomic restriction maps, DNA sequence and
      methylation of B' and B-I were compared. Despite dramatic differences in
      phenotype and transcription of B' and B-I, no evidence for rearrangements,
      changes in sequence or changes in methylation was found. These results provide no
      support for models involving "dominant negative" proteins, gene conversion or
      transposable element interactions. We suggest that b paramutation involves a
      physical interaction between the alleles that suppresses transcription and
      promotes a change in chromatin structure that is heritable.

PMID- 7507456
TI  - Evaluation of the antioxidant actions of ferulic acid and catechins.
AB  - We have evaluated the abilities of ferulic acid, (+/-) catechin, (+) catechin and
      (-) epicatechin to scavenge the reactive oxygen species hydroxyl radical (OH.),
      hypochlorous acid (HOCl) and peroxyl radicals (RO2.). Ferulic acid tested at
      concentrations up to 5 mM inhibited the peroxidation of phospholipid liposomes.
      Both (+/-) and (+) catechin and (-) epicatechin were much more effective. All the
      compounds tested reacted with trichloromethyl peroxyl radical (CCl3 O2.) with
      rate constants > 1 x 10(6) M-1 s-1. A mixture of FeCl3-EDTA, hydrogen peroxide
      (H2O2) and ascorbic acid at pH 7.4, has often been used to generate hydroxyl
      radicals (OH.) which are detected by their ability to cause damage to the sugar
      deoxyribose. Ferulic acid, (+) and (+/-) catechin and (-) epicatechin inhibited
      deoxyribose damage by reacting with OH. with rate constants of 4.5 x 10(9)M-1 s
      1, 3.65 x 10(9) M-1 s-1, 2.36 x 10(9) M-1 s-1 and 2.84 x 10(9) M-1 s-1
      respectively. (-) Epicatechin, ferulic acid and the (+) and (+/-) catechins
      exerted pro-oxidant action, accelerating damage to DNA in the presence of a
      bleomycin-iron complex. On a molar basis, ferulic acid was less effective in
      causing damage to DNA compared with the catechins. A mixture of hypoxanthine and
      xanthine oxidase generates O2-. which reduces cytochrome c to ferrocytochrome c.
      (+) Catechin and (-) epicatechin inhibited the reduction of cytochrome c in a
      concentration dependent manner. Ferulic acid and (+/-) catechin had only weak
      effects. All the compounds tested were able to scavenge hypochlorous acid at a
      rate sufficient to protect alpha-1-antiproteinase against inactivation. Our
      results show that catechins and ferulic acid possess antioxidant properties. This
      may become important given the current search for "natural" replacements for
      synthetic antioxidant food additives.

PMID- 7507458
TI  - Hepatitis C virus antibody in coagulopathic patients: ELISA and RIBA methods.
AB  - Hepatitis C is an important complication of therapy with coagulation factor
      concentrates; in fact, more than 90% of post transfusion hepatitis is caused by
      hepatitis C. Evaluation of HCV antibodies has been carried out mainly with the
      ELISA method but this test generates false positive results. Therefore, we
      studied ninety coagulopathic patients with the aim of determining the prevalence
      of hepatitis C virus (HCV) antibodies using the ELISA and RIBA methods. Our study
      confirms that the ELISA method presents false positivities: of 60 ELISA positive
      patients, only 41 were confirmed by RIBA. We found a significant correlation
      between HCV positivity, ALT titre and the number of concentrates used annually.
      In conclusion, our data suggest that the RIBA test is a useful confirmatory
      method in ELISA HCV-positive patients. This fact is particularly important in
      coagulopathic patients, in whom progression of chronic hepatitis C to cirrhosis
      is elevated.

PMID- 7507459
TI  - [Increasing the survival rate of endangered free microvascular tissue transplants
      using a prostacyclin derivative].
AB  - Free flap transplantations and replantations of extremities are threatened by
      venous occlusion due to haematomas, contusions, and secondary healing of the
      surrounding tissues. In an experimental investigation in 18 Sprague-Dawley-rats,
      the influence of the Prostacyclin analogue Iloprost on temporary ischemia by
      venous occlusion was tested. Free groin flaps were transplanted to the neck of
      these animals with microanastomoses of the nutrient superficial epigastric
      vessels to the carotid artery and the jugular vein. On the first postoperative
      day the vein was temporarily clamped. In the control group there was always a
      total loss of the flap by haemorrhagic necrosis. The intraarterial flap perfusion
      by Iloprost was able to diminish the effects of the secondary ischemia. In some
      cases shortly after the perfusion and always on the next day, positive oxygen
      pressures were measurable. 80% of the flaps survived.

PMID- 7507457
TI  - Bulky mediastinal Hodgkin's disease: results of a combined modality approach
      (ABVD/MOPP alternating chemotherapy plus radiation therapy).
AB  - BACKGROUND: Bulky mediastinal involvement is a challenging presentation of
      Hodgkin's disease (HD). Radiotherapy alone has provided a good response rate but
      also a high percentage of recurrences, and therefore many studies have been
      initiated to evaluate combined modality treatment. METHOD: In a prospective study
      23 stage IIA/IIIB HD patients treated with ABVD/MOPP alternating chemotherapy and
      radiotherapy were evaluated with regard to overall (OS) and disease-free survival
      (DFS), acute and long-term toxicity. RESULTS: A 95% CR rate was obtained. Ten
      year actuarial OS and DFS were 83 and 91%, respectively. Two patients (8.8%)
      relapsed 8 and 9 months after achieving CR. One patient (4.4%) died following
      severe bone marrow failure 25 months after diagnosis. No clinically evident acute
      or chronic cardiac or pulmonary toxicity was evident, and no second malignancies
      were observed. At the end of therapy 7/14 evaluable women became amenorrheal and
      remained so at their last follow-up. Two male patients were considered
      azoospermic on the basis of laboratory evaluation at the end of therapy, and
      after 68 and 122 months, respectively; 4 of 5 male patients had sexual
      intercourse freely but did not fertilize their partners. CONCLUSIONS: In our
      opinion and in agreement with available literature, chemotherapy has a
      fundamental place alongside radiotherapy in the treatment of bulky mediastinal
      HD. Combined modality treatment improves the disease-free survival obtained with
      radiotherapy or chemotherapy alone. In our experience a high percentage of
      patients (83%) can be considered cured without the need for second-line therapy.
      However, long-term and especially gonadal toxicity greatly influence the quality
      of life of these patients. Therefore treatment must be personalized according to
      age, sex, cardiopulmonary status and desire to preserve reproductive function.

PMID- 7507460
TI  - [Experimental studies of the no-reflow phenomenon with prostacyclin].
AB  - The no-reflow phenomenon is a dreaded complication in free tissue
      transplantations. After a critical period of warm ischemia, insufficient reflow
      is observed after vessel anastomosis and opening of the artery. In an
      experimental study in 72 rats, groin flaps were harvested with the nutrient
      superficial epigastric vessels and transplanted to the neck using a microvascular
      technique with anastomoses to the carotid artery and jugular vein. Before
      transplantation, the isolated flaps were perfused either with saline solution,
      with Iloprost, with and without heparin, or the nutrient vessels were simply
      flushed with heparin solution. After saline perfusion, there was no venous
      reflow, after pure Iloprost perfusion, there was venous return in 26% of the
      flaps, after Heparin-Iloprost perfusion in 88% and after flushing with heparin
      alone in 93%. The addition of heparin to Iloprost seems to improve the reflow
      rate. The most effective protection against a no-reflow phenomenon, however, is
      flushing the nutrient vessels with a heparin solution.

PMID- 7507461
TI  - Detection of antigens related to hepatitis C virus RNA encoding the NS5 region in
      the livers of patients with chronic type C hepatitis.
AB  - Hepatitis C virus is a positive single-strand RNA virus distantly related to
      flaviviruses. Therefore RNA replicase, an RNA-dependent RNA polymerase, may be
      essential for the replication of hepatitis C virus, as well as other RNA viruses.
      In this study we synthesized the recombinant polypeptide (HCV-NS5 antigen) with a
      576 bp cDNA encoding a part of the NS5 region of the HCV genome that has the Gly
      Asp-Asp motif. The antibody against this polypeptide was obtained from rabbit
      serum. In Western-blot analysis with NS5 IgG HCV antibody, an 84-kD protein was
      clearly detected as a single band in the microsomal fraction but not in the
      nuclear and mitochondrial fractions or in the cytosol fraction.
      Immunohistochemically, HCV-NS5 antigen was clearly stained in the cytoplasm of
      hepatocytes but not in the nucleus or cell membrane. Moreover, as determined on
      immunoelectron microscopy, HCV-NS5 antigen was demonstrated with fine granular
      distribution along the endoplasmic reticulum but not in other organelles,
      including the nucleus and mitochondria. Immunoreaction in other cell types was
      negative. These results indicate that replication of HCV may occur only in
      hepatocytes and that HCV-NS5 may be produced in the endoplasmic reticulum of
      these cells. HCV-NS5 antigen was stained only in the livers of hepatitis C virus
      positive patients but not in sections from patients with chronic type B hepatitis
      or alcoholic fibrosis. In chronic type C liver disease, the overall detection
      rate of HCV-NS5 antigen was 56% (33% in chronic persistent hepatitis, 52% in
      chronic active hepatitis and 86% in cirrhosis).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507462
TI  - High sustained response rate and clearance of viremia in chronic hepatitis C
      after treatment with interferon-alpha 2b for 60 weeks.
AB  - To evaluate the effect of prolonged interferon-alpha treatment on serum
      aminotransferase levels and hepatitis C virus RNA in serum, 40 patients with
      chronic hepatitis C virus infection were treated with 3 MU interferon-alpha 2b
      thrice weekly for 60 wk. Before treatment all patients had elevated serum ALT
      levels for at least 1 yr, antibodies to HCV by second-generation tests and liver
      histological findings consistent with chronic hepatitis C. Before treatment
      hepatitis C virus RNA was found in serum in 39 of 40 (97.5%) patients.
      Normalization of ALT levels at treatment cessation was seen in 24 of 40 (60%)
      patients, of whom 15 of 24 (62.5%) had sustained ALT responses up to 24 wk after
      treatment. At follow-up, 24 wk after treatment, hepatitis C virus RNA was cleared
      from serum in 17 of 40 (42.5%) patients, including all sustained responders, one
      nonsustained responder and one nonresponder. We conclude that 60 wk of treatment
      with interferon-alpha 2b seems to induce a high percentage of sustained response,
      which coincides with cessation of viral replication.

PMID- 7507463
TI  - Acetaldehyde-modified epitopes in liver biopsy specimens of alcoholic and
      nonalcoholic patients: localization and association with progression of liver
      fibrosis.
AB  - Acetaldehyde, the first product of ethanol oxidation, has been shown to stimulate
      collagen gene expression and to form protein-acetaldehyde adducts. Because little
      is known about these adducts in human liver tissue, we assessed, with an
      immunohistochemical procedure, the presence and location of acetaldehyde-protein
      adducts in liver biopsy specimens of alcoholic patients. In addition, we
      correlated the presence of adducts with the progression or subsequent occurrence
      of liver fibrosis. The group included 106 patients with high alcohol consumption
      (> 90 gm ethanol/day for the last 5 yr), 10 nonalcoholic patients with normal
      livers and 23 patients with other liver diseases. Sixty-four of the 106 alcoholic
      patients had a second liver biopsy, whose specimen was used to assess the
      progression of liver fibrosis. Polyclonal antibodies were produced against
      homologous low-density lipoprotein purified from rabbit serum and modified in
      vitro in the presence of acetaldehyde. Protein-acetaldehyde adducts could be
      detected by immunohistochemistry in biopsy specimens of 90 alcoholic patients
      (85%), in none of the 10 nonalcoholic patients with normal livers and in 65% of
      the patients with nonalcoholic liver disease. Acetaldehyde-modified epitopes were
      detected in the intracellular and extracellular compartment. Intracellular
      protein-acetaldehyde adducts were localized in the cytoplasm of hepatocytes with
      a more intense staining in zone 3. No correlation existed between the intensity
      of intracellular staining and the histologically assessed severity of liver
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507464
TI  - Ito cell heterogeneity: desmin-negative Ito cells in normal rat liver.
AB  - The presence of desmin is used to identify Ito cells in rat liver and to evaluate
      the purity of separated and cultured Ito cells. Heterogeneity of the normal Ito
      cell population has been suggested; this could include variations in the content
      of cytoskeletal components. For these reasons we decided to reevaluate the use of
      desmin staining as a phenotypical marker of Ito cells in normal rat liver. Our
      approach was to combine desmin staining with identification of vitamin A
      (autofluorescence), lipid droplets (Sudan III), vimentin, laminin and tenascin,
      using cryostat sections: Immunofluorescence, double-immunofluorescence or
      immunoperoxidase techniques were used. All the techniques described corroborate
      the existence of desmin-negative Ito cells, mainly located in pericentral areas.
      In fact, lobular desmin-positive cells showed uneven distribution because they
      were more frequent in periportal than in pericentral areas. On the contrary, Ito
      cells identified on the basis of morphological criteria or positivity for laminin
      were evenly distributed. Double immunofluorescence confirmed this observation,
      showing nearly complete codistribution of laminin and desmin in periportal areas.
      Outside this area, positivity for desmin was observed only in about 50% of
      laminin-positive cells. Our observations suggest that desmin cannot be viewed as
      a phenotypical marker but rather is a differentiation marker of Ito cells,
      possibly indicating a specific functional state.

PMID- 7507465
TI  - Peripheral blood leukocytes from multiple sclerosis patients are coated with
      factors inhibiting their chemotaxis in the presence of myelin basic protein.
AB  - In this study myelin basic protein (MBP) was tested for its effect on chemotaxis
      of human peripheral blood leukocytes (PBL) and neutrophils from multiple
      sclerosis (MS) patients. MBP appeared to inhibit specifically the formyl
      methionyl-leucyl-phenylalanine (FMLP)-induced chemotaxis of both the total
      leukocyte population and neutrophils. In comparison, no inhibition of chemotaxis
      was observed in healthy donors and patients with other neurological diseases.
      From MS patients we collected neutrophil supernatants obtained by incubation of
      the cells in a serum-free medium at 37 degrees C for 60 min and evaluated their
      effect on chemotaxis of neutrophils from healthy donors. Chemotaxis of healthy
      donor neutrophils was inhibited specifically in the presence of MBP after
      treatment with these supernatants, presumably relating to the presence of immune
      complexes on the surface of neutrophils from MS patients. Those complexes can be
      eluted into the incubation medium and coat healthy donor neutrophils, thus arming
      them specifically.

PMID- 7507466
TI  - CD5+ B cells and the immune system.
AB  - The CD5+ B-cell population is prominent in early life and may play a key role in
      the ontogeny of the immune system. Transplantation studies in mice are in support
      of CD5+ B cells as a separate lineage from CD5- B cells. In both mice and men
      there is evidence in favour of CD5 being an activation antigen rather than a
      lineage marker, but the jury is still out! The frequency of CD5+ B cells appears
      to be under genetic influence. CD5+ B cells are receptive to many cytokines
      including IL-2 and IL-5 and themselves produce a number of cytokines especially
      IL-10. The function of the CD5 molecule on B cells is presently unknown but it
      might be involved in interaction with CD72 on other B cells. CD5+ B cells
      generally utilise minimally mutated germ-line genes and produce low avidity auto-
      and polyreactive antibodies (natural antibodies) generally of the IgM class.

PMID- 7507467
TI  - Early and rapid de novo synthesis of Alzheimer beta A4-amyloid precursor protein
      (APP) in activated microglia.
AB  - Upon acute activation, microglia, the immuneffector cells of the brain
      parenchyma, express the amyloid precursor protein (APP) that is otherwise
      prominent in pathological structures related to Alzheimer's disease. In this
      disease complex amyloid-bearing neuritic plaques contain beta A4-amyloid protein,
      the APP, and numerous inflammatory proteins. The accompanying activation of
      microglia has mostly been viewed as a secondary reaction to amyloid deposits.
      Activation of microglia was performed in a graded fashion. Transection of
      peripheral nerves such as the facial or sciatic nerve causes a microglial
      reaction within hours in the nucleus of origin or in projection areas of the CNS.
      A predominantly glial up-regulation of APP mRNA and protein could be detected as
      early as 6 h post lesion not only at the site of affected neuronal cell bodies
      but also in corresponding projection areas. Its time course suggests rapid
      transneuronal signalling to glial cells in the projection area. Light and
      electron microscopy demonstrate that microglia, which are cells of mononuclear
      phagocyte lineage and comprise up to 20% of all glial cells, are the dominant
      source for non-neuronal APP expression. Ultrastructurally, brain perivascular
      cells within the basal lamina constitutively express APP and thus are a possible
      source of vascular amyloid. Additionally, microglia express leukocyte-derived (L)
      APP mRNA and protein that have recently been described in mononuclear cells of
      the immune system. Increased L-APP expression may serve as a potential marker for
      glial/microglial activation. Such immune-mediated amyloidogenesis initiated by
      microglia might have implications for the treatment of neurodegenerative
      diseases.

PMID- 7507468
TI  - Single-channel characteristics of the large-conductance anion channel in rat
      cortical astrocytes in primary culture.
AB  - Cultured rat cortical astrocytes, in addition to a variety of voltage-sensitive
      potassium channels, also express anion channels. However, the behavior and
      regulation of these anion channels have been far less studied. This paper
      describes a patch-clamp study on a voltage-sensitive 200-300 pS high-conductance
      single-channel anion current, which seems to possess at least five different open
      sublevels or, alternatively, be formed from five or more small-conductance ion
      channels linked together. This channel is voltage dependent, showing a bell
      shaped open probability curve with highest open probability close to the reversal
      potential (zero-current). Although potassium channels are commonly detected in
      astrocytes in cell-attached and excised patches with both normal osmolarity and
      hypoosmotic solutions, the occurrence of the anion channel is clearly increased
      in isolated patches when hypoosmotic bath solutions are used. Also, cell aging in
      culture and the preparation of secondary cell cultures by trypsinization seem to
      increase the rate of occurrence of the anion channel. Though this channel is more
      routinely seen when a membrane patch is excised from the cell, occasionally cell
      attached configurations with instant channel activity can be formed. While the
      modulation of this anion channel was being studied, it was found to be blocked by
      an anion transport inhibitor, L-644,711, reported to affect cell volume
      regulation in astrocytes.

PMID- 7507470
TI  - Behavioral development in children prenatally exposed to drugs and alcohol.
AB  - Empirical research on the behavioral consequences to the offspring of use of
      recreational and addictive drugs and alcohol by pregnant women is reviewed. The
      current epidemic of cocaine use has raised the specter of a host of "cocaine
      babies" whose prenatally induced impairments will interfere with social and
      academic functioning and constitute an immense social burden. In fact,
      examination of effects of drug exposure on infant behavior and subsequent
      development suggests a much more subtle and complicated process which must take
      into account not only the child's prenatal exposure but the various other
      environmental factors which contribute to eventual outcome. These other factors
      include caregiving competence and social environment.

PMID- 7507469
TI  - The consequences of prenatal substance use for the developing fetus, newborn, and
      young child.
AB  - Although substance use has been a worldwide problem at all levels of society
      since ancient times, recent attention has been focused on the use of legal and
      illegal substances by the pregnant woman. Almost all drugs taken by the pregnant
      woman are known to cross the placenta and have some effect on the fetus. This
      article reviews the effects of the drugs most frequently used by pregnant women
      in the United States--nicotine, alcohol, marijuana, opiates, and cocaine--on the
      fetus and neonate; when possible, information regarding long-term medical
      problems is included.

PMID- 7507471
TI  - Intervention strategies for children vulnerable for school failure due to
      exposure to drugs and alcohol.
AB  - Children and youth exposed in utero to drugs and alcohol and/or who are growing
      up in a family in which these substances are misused are vulnerable for failure
      at all age levels, prenatally through adulthood. This article reviews
      developmental issues presented by children and youth vulnerable for school
      failure either due to the biological effects of prenatal exposure to drugs and/or
      environmental issues resulting from growing up in a family in which misuse of
      drugs and alcohol occurs. Characteristics and needs of these students with
      recommendations for educational and community-based system of services to them
      and their families are discussed. Model programs serving children and youth
      prenatally through school age are identified.

PMID- 7507473
TI  - Creating visual slides.

PMID- 7507475
TI  - Establishment and characterization of a rat yolk sac tumor cell line, NMT-1,
      producing alpha-fetoprotein, with potential for lymphatic metastasis.
AB  - A new cell line producing alpha-fetoprotein, designated NMT-1, was established
      from rat yolk sac tumor with the potential for lymphatic metastasis in inbred
      Wistar rats. In this paper, we investigated the characteristics of NMT-1 cells.
      The cell line grew in a monolayer and had a polygonal epithelioid appearance in
      phase-contrast microscopy. The doubling time of NMT-1 cells during exponential
      growth was approximately 16 h in RPMI-1640 with 10% fetal calf serum. The D0
      value for radiation sensitivity was 97 +/- 3 cGy. The extrapolation number, n,
      for NMT-1 was 1.08 +/- 0.15. In the log phase, the G0/G1, S and G2/M fractions
      were 23.2%, 62.1% and 14.3%, respectively. Tumor take was observed in all of the
      rats inoculated with NMT-1 cells. In the case of flank tumor, the mean survival
      time was 104 days after inoculation with 10(6) tumor cells. Inguinal, axillary,
      paraaortic, mesenteric and mediastinal lymphnode metastases were observed in all
      rats inoculated with NMT-1 cells. Rats which survived for a long time developed
      metastases in a lymphatic vessels of the liver, lung and/or kidney
      microscopically. The biological behavior and the histopathological features of
      the tumor induced by inoculation with NMT-1 cells were the same as those of the
      original tumor induced by fetectomy.

PMID- 7507472
TI  - Platelet substance P and 5-hydroxytryptamine in migraine and tension-type
      headache.
AB  - Levels of substance P (SP) and 5-hydroxytryptamine (5-HT) in platelets were
      measured in 25 patients with migraine, 31 patients with tension-type headache
      (TH) and 27 healthy controls. The mean concentration of SP in platelets was 355.3
      pg/10(9) platelets in patients with migraine, 290.8 pg/10(9) platelets in
      patients with TH and 180.8 pg/10(9) platelets in the controls. The concentrations
      of platelet SP in the migrainous patients and in the TH patients were
      significantly higher than those in the controls. The mean concentration of 5-HT
      in platelets was 619.7 ng/10(9) platelets in patients with migraine, 579.3
      ng/10(9) platelets in patients with TH and 811.9 ng/10(9) platelets in the
      controls. The concentration of platelet 5-HT in the patients with TH was
      significantly lower than that in the controls. The platelet SP/5-HT ratio in the
      migrainous patients and in the TH patients were significantly higher than that in
      the controls. There was significant negative correlation between the
      concentrations of platelet SP and those of platelet 5-HT. These results may
      support the hypothesis that SP released from the terminals of the trigeminal
      nerves causes migraine either through direct actions on the vessels or by
      releasing 5-HT from the platelets. The high levels of platelet SP in TH patients
      might reflect release of SP from the pain sensory system.

PMID- 7507476
TI  - Rapid communication: a MspI polymorphism at the porcine interleukin-6 (IL-6)
      locus.

PMID- 7507474
TI  - H-2z homozygous New Zealand mice as a model for B-cell chronic lymphocytic
      leukemia: elevated bcl-2 expression in CD5 B cells at premalignant and malignant
      stages.
AB  - In New Zealand mice, the major histocompatibility complex (MHC) controls the
      development of both autoimmune disease and B cell chronic lymphocytic leukemia (B
      CLL). While H-2d/H-2z heterozygosity acts as one major predisposing genetic
      element for autoimmune disease, H-2z/H-2z homozygosity acts as an element for B
      CLL. In the H-2z/H-2z homozygotes, there was an age-dependent increase in
      frequencies of CD5 B cells in the blood and spleen, and such CD5 B cells showed
      oligoclonal to monoclonal expansion, giving rise to B-CLL. B-CLL cells from these
      mice had surface phenotypes typical of CD5 B lineage cells, and expressed high
      levels of proto-oncogene bcl-2. Elevated bcl-2 expression was also observed in
      premalignant B cells in the aged mice, thereby suggesting that apoptosis
      resistant, long-surviving CD5 B cells with a self-renewal capacity form the basis
      of malignant transformation. This model not only provides clues for analyzing
      multiple steps of genetic alterations involved in the generation of B-CLL, but
      also sheds light on the correlation between B-CLL and autoimmune disease.

PMID- 7507477
TI  - Rapid communication: MspI restriction fragment length polymorphism at the swine
      myogenin locus.

PMID- 7507478
TI  - Sulfated blood group Lewis(a). A superior oligosaccharide ligand for human E
      selectin.
AB  - In earlier studies of oligosaccharide probes (neoglycolipids) generated from an
      ovarian cystadenoma glycoprotein, one of the components that strongly supported
      binding of the endothelial adhesion molecule, E-selectin, was identified as an
      equimolar mixture of tetrasaccharides of blood group Le(a) and Le(x) type
      sulfated at position 3 of the outer galactose (C.-T. Yuen, A. M. Lawson, W. Chai,
      M. Larkin, M. S. Stoll, A. C. Stuart, F. X. Sullivan, T. J. Ahern, and T. Feizi
      (1992) Biochemistry 31, 9126-9131). In the present studies, the individual
      sulfated Le(a) and sulfated Le(x) oligosaccharides synthesized chemically have
      been investigated, first, for their ability to support E-selectin binding when
      converted into neoglycolipids, and second, for their ability to inhibit E
      selectin binding to immobilized lipid-linked sialyl-Le(a), sialyl-Le(x), or
      sulfated Le(a) pentasaccharides; their activities have been compared with those
      of the sialyl-Le(a) and sialyl-Le(x) analogues. From these studies, the sulfated
      Le(a) tetra- and pentasaccharides emerge as the most potent E-selectin ligands so
      far. In particular, the inhibitory activity of the sulfated Le(a) pentasaccharide
      is substantially greater than that of the sialyl-Le(x) trisaccharide, which is
      currently the most widely used inhibitor of E-selectin binding: 45-, 35-, or 15
      fold greater depending on whether adhesion is to sialyl-Le(a), sulfated Le(a), or
      sialyl-Le(x) pentasaccharides, respectively. These findings have an important
      bearing on design of new generations of inhibitors of E-selectin binding as
      antiinflammatory compounds.

PMID- 7507479
TI  - NADH regulates the gating of VDAC, the mitochondrial outer membrane channel.
AB  - Aerobic energy metabolism in cells involves the transfer of reducing equivalents
      from organic molecules to oxygen. NADH is important as a carrier of these
      reducing equivalents and as a feedback regulator of glycolysis. We report that
      micromolar quantities of NADH double the voltage dependence of the mitochondrial
      channel, VDAC, a critical pathway for the flux of metabolites between the
      cytoplasm and the mitochondrial spaces. In the presence of NADH, the opening and
      closing of this channel is more sensitive to changes in membrane potential and
      thus presumably better able to respond to changes in metabolic conditions. This
      effect was observed both on a human and two fungal forms of VDAC, indicating a
      highly conserved regulatory mechanism. NAD+ and other nucleotides tested failed
      to mimic the action of NADH. This ability of NADH to facilitate VDAC closure
      could be one mechanism by which glycolysis can suppress oxidative phosphorylation
      (Crabtree effect).

PMID- 7507480
TI  - Modification of Ca2+ channel activity by deletions at the carboxyl terminus of
      the cardiac alpha 1 subunit.
AB  - Voltage-sensitive Ca2+ channels are multisubunit complexes that include, among
      others, a large alpha 1 subunit, which by itself is sufficient to form a channel.
      Several alpha 1 genes encoding L-, N-, and P-type Ca2+ channels have been cloned.
      These alpha 1 genes share a high degree of sequence homology in the putative
      transmembrane regions, but vary substantially in the putative intracellular loops
      and the flanking amino and carboxyl termini. In the present study, we
      investigated the functional roles of the 665-amino acid long carboxyl terminus of
      a cardiac alpha 1 by constructing deletion mutants. Expression in Xenopus oocytes
      of delta C1856, delta C1733, and delta C1700, which lack from 307 to 472 amino
      acids at the carboxyl terminus, led to inward Ba2+ currents that were 4- to 6
      fold greater than observed with the 2171-amino acid long wild type alpha 1. Ionic
      currents increased without a change in the amount of charge moved during voltage
      dependent gating, suggesting that the increase in ionic currents was not due to
      an increase in the number of channels that were expressed. Single channel
      analysis revealed an unaltered unitary conductance. Thus, removal of up to 70% of
      the carboxyl terminus increased current density by facilitating the coupling
      between the voltage-dependent gating and channel opening, leading to an increased
      opening probability of the channel.

PMID- 7507481
TI  - Membrane topology of aquaporin CHIP. Analysis of functional epitope-scanning
      mutants by vectorial proteolysis.
AB  - CHIP is the archetypal member of the aquaporins, a widely expressed family of
      membrane water channels. The NH2- and COOH-terminal halves of CHIP are sequence
      related, and hydropathy analysis predicted six membrane-spanning domains with
      five connecting loops (A-E). Here, we determined the membrane topology of CHIP
      expressed in Xenopus oocytes using biologically active recombinant channels. CHIP
      is glycosylated at Asn-42, indicating loop A is exofacial. An epitope from the
      coronavirus E1 glycoprotein was inserted into CHIP and localized to the outer or
      inner leaflet of the membrane by alpha-chymotrypsin digestion of intact oocytes
      or inside-out membrane vesicles. The E1 epitope at Thr-120 was protease-sensitive
      in intact oocytes, indicating that loop C is exofacial. The E1 epitope at Lys-6,
      Arg-162, or Lys-267 was protease-sensitive in inside-out membrane vesicles,
      confirming the cytoplasmic location of the NH2 and COOH termini and loop D.
      Insertions into loops B and E did not produce active water channels, but their
      cleavage patterns were consistent with inner (loop B) and outer (loop E) leaflet
      locations. This study indicates that the functional CHIP molecule is a unique
      structure with two internal repeats oriented 180 degrees to each other within the
      membrane.

PMID- 7507482
TI  - Inhibitors of brain nitric oxide synthase. Binding kinetics, metabolism, and
      enzyme inactivation.
AB  - Nitric oxide (NO) is synthesized from L-arginine by different NO synthase
      isozymes, which are inhibited by the substrate analogs NG-methyl- and NG-nitro-L
      arginine. We studied binding of 3H-labeled NG-nitro-L-arginine to purified brain
      NO synthase and compared the data with results obtained in enzyme kinetic
      experiments. Binding data revealed a single binding site for NG-nitro-L
      [3H]arginine (KD = 0.17 microM). Binding was competitively antagonized by L
      arginine (KI = 2.9 microM). The half-time of dissociation was remarkably slow
      (9.4 min) and closely correlated with the time necessary for surmounting NO
      synthase inhibition by dilution. Although an apparently less potent inhibitor, NG
      methyl-L-arginine exhibited the same affinity for brain NO synthase as the nitro
      derivative (KI = 0.17 microM), and in initial rate experiments, almost equal KI
      values were obtained for NG-methyl-L-arginine (0.61 microM) and NG-nitro-L
      arginine (0.53 microM). However, after prolonged incubation periods, NG-nitro-L
      arginine induced a rapid inactivation of the enzyme, whereas the methyl
      derivative turned out to be a substrate of NO synthase, which was slowly
      converted into stoichiometric amounts of NO and L-citrulline.

PMID- 7507483
TI  - Human proinsulin conversion in the regulated and the constitutive pathways of
      transfected AtT20 cells.
AB  - AtT20 (mouse pituitary corticotroph) cells were stably transfected with human
      proinsulin cDNA. Clone H12 displayed low basal release of insulin-like
      immunoreactivity (< 1% cell content/30 min) with 17-fold stimulation by
      isobutylmethylxanthine/forskolin. Clone H23, by contrast, showed higher basal
      release (2.8% cell content/30 min) and only 6-fold stimulation. To follow the
      kinetics of conversion and release of only newly synthesized proinsulin, cells
      were pulse-chased, and labeled proinsulin-related products were analyzed by high
      pressure liquid chromatography. In the cells of both clones, [3H]proinsulin was
      converted to insulin with des-31,32-split proinsulin as the only detectable
      intermediate. While basal release of labeled products from H12 cells was low
      (3%/60 min), it was rapid and elevated from H23 cells (12.5% by 30 min and 24.8%
      by 60 min of chase) with [3H]des-31,32-split proinsulin the predominant molecular
      form. Stimulation of [3H] insulin release increased with time, reaching 3.8-fold
      by 90 min of chase, whereas that of [3H]des-31,32-split proinsulin was
      approximately 1.5-fold regardless of the chase time. Rapid secretion of newly
      synthesized products that is insensitive to secretagogues is the hallmark of the
      constitutive pathway. Thus in H23 cells an unusually large amount of proinsulin
      is diverted to the constitutive pathway, where it is partially converted to des
      31,32-split proinsulin before release.

PMID- 7507484
TI  - Precursor sequence, processing, and urothelium-specific expression of a major 15
      kDa protein subunit of asymmetric unit membrane.
AB  - The asymmetric unit membrane (AUM) is a highly specialized biomembrane elaborated
      by terminally differentiated urothelial cells. It contains quasi-crystalline
      arrays of 12-nm protein particles each of which is composed of six dumbbell
      shaped subdomains. In this paper we describe the precursor sequence, processing
      and in vitro membrane insertion properties of bovine uroplakin II (UPII), a 15
      kDa major protein component of AUM. The cDNA-deduced amino acid sequence revealed
      that UPII is synthesized as a precursor protein containing a cleavable signal
      peptide of approximately 26 amino acids, a long pro-sequence of approximately 59
      residues harboring three potential N-glycosylation sites, and the mature
      polypeptide of 100 residues. In vitro translation of UPII mRNA demonstrated that
      UPII is indeed first synthesized as a 19-kDa precursor, which loses its signal
      peptide upon insertion into added microsomes; this process is accompanied by the
      acquisition of high mannose-type oligosaccharides giving rise to a 28-kDa
      precursor which is completely protected from the digestion by exogenous
      proteases. These results, together with the presence of a stretch of 25
      hydrophobic amino acids at the C terminus, suggest that UPII protein is anchored
      to the lipid bilayer via its C-terminal membrane-spanning domain with its major N
      terminal domain exposed luminally. The formation of the 15-kDa mature UPII
      requires the removal of the pro-sequence by a furin-like endoprotease. Since only
      mature UPII devoid of this pro-sequence can interact with 27-kDa uroplakin I, the
      proteolytic processing of UPII precursor may play an important role in regulating
      the assembly of AUM. Finally, we showed that genomic sequences cross-hybridizing
      with bovine UPII cDNA are present in many mammals suggesting that UPII performs a
      highly conserved function in the terminally differentiated cells of mammalian
      urinary bladder epithelium.

PMID- 7507485
TI  - Enhancement of reporter gene de novo methylation by DNA fragments from the alpha
      fetoprotein control region.
AB  - The 5'-upstream region of the rat alpha-fetoprotein (AFP) gene strongly increased
      de novo methylation of an adjacent chloramphenicol acetyltransferase (CAT) gene
      upon transfection into F9 mouse embryonal carcinoma cells. The same effect was
      exerted by a distal 775-base pair (bp) fragment and by 300- and 1-kb fragments
      preceding the transcriptional start site, but not by other parts of the control
      region. Further division of the larger, strongly active fragments resulted in a
      gradual decrease of methylation and clonal variation in the methylation patterns.
      The effect of the 775-bp fragment did not depend on its orientation. It was
      ablated by insertion of the mouse metallothionein I promoter between the AFP gene
      fragment and the CAT gene, but not by its insertion upstream of the AFP gene
      fragment. Two fragments from the AFP control region increasing methylation
      contained B1 and B2 small interspersed repetitive elements, respectively. B1 and
      B2 sequences of different origin also acted strongly to increase methylation.
      These findings support the idea that mammalian genes contain specific sequences
      involved in regulating their methylation. The effects of these sequences appear
      to be exerted in cis, to be dependent on proximity, but not on orientation, and
      to require an optimal size of 500-700 bp. Small retrotransposon sequences within
      such elements may be particularly effective in attracting de novo methylation.

PMID- 7507486
TI  - Folding patterns of immunoglobulin molecules identified by urea gradient
      electrophoresis.
AB  - The reversible denaturant-induced unfolding of immunoglobulin molecules has been
      analyzed by transverse urea gradient gel electrophoresis and the effects that
      urea-induced unfolding exerts on the functional properties associated with their
      variable region, i.e. antigen binding and idiotypic expression, have been
      determined by Western blot analysis. Results obtained from these experiments
      indicate that urea-induced unfolding of the immunoglobulin molecule is a highly
      cooperative reversible process that occurs through a two-state transition with no
      accumulation of intermediates. The unfolding transition has its midpoint at about
      6.5 M urea and appears to be slow on the time scale of electrophoresis. Folding
      intermediates in rapid equilibrium with the unfolded state as well as molecular
      forms with different electrophoretic mobility can be detected during refolding
      reactions. Results from Western blot analysis confirm the highly cooperative
      reversible urea-induced unfolding of immunoglobulin molecules and demonstrate
      that the unfolding transition leads to disappearance of both antigen binding and
      idiotypic expression, whereas the ability to interact with antibodies directed to
      continuous epitopes of the variable region is preserved. After progressive
      removal of the denaturing agent, the variable region refolds into structures that
      regain the functional properties of the native conformation.

PMID- 7507487
TI  - The proto-oncogene of v-eyk (v-ryk) is a novel receptor-type protein tyrosine
      kinase with extracellular Ig/GN-III domains.
AB  - v-ryk is the oncogene in the avian acute oncogenic retrovirus RPL30, its cellular
      counterpart, c-ryk, is described in this report. To avoid the confusion caused by
      another gene with the same name, we renamed v-ryk to be v-eyk, thereby changing
      the proto-oncogene's name to c-eyk. c-eyk is expressed highly in chicken spleen
      and moderately in many other tissues including embryonic tissues. Its cDNA is
      3061 base pairs encoding a receptor-type protein tyrosine kinase (PTK) of 974
      amino acids. Compared to c-Eyk, v-Eyk is a truncated PTK lacking the
      extracellular and transmembrane regions of c-Eyk in addition to two amino acid
      changes. c-Eyk has two C2-type Ig domains and two FN-III domains in its
      extracellular region, forming a new subfamily of receptor-type PTK together with
      UFO/Axl/Ark. As suggested by Ig/Fn-III domains in many cell adhesion molecules,
      this subfamily of PTK may mediate cell-cell interaction.

PMID- 7507489
TI  - Enzymatic characterization of interferon-induced antiviral GTPases murine Mx1 and
      human MxA proteins.
AB  - Interferons induce a number of different proteins which mediate the
      antiproliferative, antiviral, and immunomodulatory functions of interferons.
      Interferon-induced Mx proteins, which confer resistance to influenza, vesicular
      stomatitis, and measles viruses, contain consensus GTPase sequence elements.
      Insect cell-produced purified murine Mx1 and human MxA proteins were found to
      hydrolyze GTP with Km = 65 microM (Vmax, 7.1 min-1) and 62 microM (Vmax, 3.1 min
      1), respectively. The GTPase activity of Mx1 and MxA proteins was strictly
      dependent on Mg2+ ions. Murine Mx1 protein was inactivated at 10 degrees C lower
      temperatures than MxA protein. As analyzed, by filter binding assay, Mx1 protein
      (at 1 microM) showed a relatively high affinity for GDP (Kd = 1.0 x 10(-7) M) and
      approximately 340-fold lower affinity for guanosine 5'-3-O-(thio)triphosphate
      (GTP gamma S) (Kd = 3.4 x 10(-5) M). The Kd values for MxA protein were 2.0 x 10(
      7) M for GDP and 5.9 x 10(-6) M for GTP gamma S, showing approximately a 30-fold
      affinity difference. ATP, UTP, or CTP did not inhibit the Mx protein-dependent
      GTPase activity, suggesting that Mx1 and MxA proteins are highly specific for
      guanosine nucleotides. In conclusion recombinant nuclear murine Mx1 and
      cytoplasmic human MxA proteins show clear differences in their enzymatic
      activities and nucleotide binding characteristics. How these differences
      influence their cellular functions and antiviral potential is presently not
      known.

PMID- 7507488
TI  - GM3 directly inhibits tyrosine phosphorylation and de-N-acetyl-GM3 directly
      enhances serine phosphorylation of epidermal growth factor receptor,
      independently of receptor-receptor interaction.
AB  - GM3 ganglioside (II3NeuAcLacCer) inhibits epidermal growth factor (EGF)-dependent
      receptor autophosphorylation and cell growth (Bremer, E.G., Schlessinger, J., and
      Hakomori, S. (1986) J. Biol. Chem. 261, 2434-2440), whereas de-N-acetyl-GM3
      (deNAcGM3; II3NeuNH2Lac-Cer) promotes these processes (Hanai, N., Dohi, T.,
      Nores, G. A., and Hakomori, S. (1988) J. Biol. Chem. 263, 6296-6301). Receptor
      receptor interaction has been proposed as an essential initial mechanism for EGF
      dependent activation of EGF receptor kinase (EGF-RK) (Schlessinger, J. (1988)
      Trends Biochem. Sci. 13, 443-447). We studied the effects of GM3 and deNAcGM3 on
      EGF-RK function and EGF-R dimerization, and observed that (i) EGF-dependent in
      vitro and in vivo (in situ) phosphorylation of A431 cells at both monomeric and
      dimeric forms of EGF-R was inhibited in a dose-dependent manner by GM3, but
      unaffected by GM1. (ii) Quantities of both forms of EGF-R remained constant
      regardless of addition of various quantities of GM3 or GM1, as revealed by
      blotting with antibodies directed to the C-terminal region of EGF-R, or by cell
      surface 125I-labeling followed by immunoprecipitation. (iii) DeNacGM3 in the
      absence as well as in the presence of a minimal quantity of detergent
      significantly enhanced EGF-R phosphorylation, particularly Ser phosphorylation.
      (iv) DeNAcGM3 was detected in a large variety of actively growing tumor cells.
      Findings i and ii above indicate that GM3 directly inhibits EGF-dependent Tyr
      phosphorylation but does not affect receptor-receptor interaction. Findings iii
      and iv suggest that deNAcGM3 strongly promotes serine phosphorylation (in
      addition to Tyr phosphorylation) of EGF-R and may function as a second messenger
      in the process of cell growth stimulation.

PMID- 7507490
TI  - Hydrolytic cleavage of nascent RNA in RNA polymerase III ternary transcription
      complexes.
AB  - Highly purified yeast RNA polymerase III ternary complexes were found to possess
      a hydrolytic chain retracting activity that cleaves nascent RNA from its 3'-OH
      end. Most of the shortened transcripts were capable of resuming RNA chain
      elongation, indicating that they remain stably associated with the enzyme-DNA
      complex. Analysis of the products of cleavage indicated that retraction primarily
      occurred in dinucleotide increments, but that mononucleotides were also excised
      at lower frequency. The ribonuclease activity was totally dependent on the
      presence of a divalent cation and was stimulated by the addition of non-cognate
      ribonucleotides. The inclusion of ATP in the reaction enhanced both the rate and
      extent of transcript cleavage. Evidence suggesting that the hydrolytic activity
      is intrinsic to RNA polymerase III and factor-independent is also presented.
      Transcript cleavage by RNA polymerase III ternary complexes appears to be more
      closely related to the intrinsic nucleolytic activity of vaccinia virus RNA
      polymerase ternary complexes than to TFIIS-dependent cleavage that has been
      described for RNA polymerase II ternary complexes.

PMID- 7507491
TI  - Matrix-bound thrombospondin promotes angiogenesis in vitro.
AB  - Thrombospondin (TSP) is a multidomain adhesive protein postulated to play an
      important role in the biological activity of the extracellular matrix. To test
      this hypothesis, TSP-containing fibrin and collagen matrices were evaluated for
      their capacity to support angiogenesis and cell growth from explants of rat
      aorta. This serum-free model allowed us to study the angiogenic effect of TSP
      without the interference of attachment and growth factors present in serum. TSP
      promoted dose-dependent growth of microvessels and fibroblast-like cells. The
      number of microvessels in TSP-containing collagen and fibrin gels increased by
      136 and 94%, respectively. The TSP effect was due in part to cell proliferation
      since a 97% increase in [3H]thymidine incorporation by the aortic culture was
      observed. The effect was TSP-specific because TSP preparations adsorbed with anti
      TSP antibody showed no activity. TSP did not promote angiogenesis directly since
      no TSP-dependent growth of isolated endothelial cells could be demonstrated.
      Rather TSP directly stimulated the growth of aortic culture-derived
      myofibroblasts which in turn promoted microvessel formation when cocultured with
      the aortic explants. Angiogenesis was also stimulated by myofibroblast
      conditioned medium. Partial characterization of the conditioned medium suggests
      that the angiogenic activity is due to heparin-binding protein(s) with molecular
      weight > 30 kD. These results indicate that matrix-bound TSP can indirectly
      promote microvessel formation through growth-promoting effects on myofibroblasts
      and that TSP may be an important stimulator of angiogenesis and wound healing in
      vivo.

PMID- 7507492
TI  - Expression and modulation of CD44 variant isoforms in humans.
AB  - CD44 is a ubiquitous surface molecule that exists as a number of isoforms,
      generated by alternative splicing of 10 "variant" exons. Little is known about
      the expression and function of the variant isoforms, except that certain isoforms
      may play a role in cancer metastasis. We produced mAbs against CD44 variant
      regions encoded by exons 4v, 6v, and 9v, by immunizing mice with a fusion protein
      spanning variant exons 3v to 10v. A comprehensive analysis of human tissues
      revealed that CD44 variant isoforms were expressed widely throughout the body,
      principally by epithelial cells. However there was differential expression of
      CD44 variant exons by different epithelia. Most epithelia expressed exon 9v, but
      much fewer expressed 6v or 4v. The regions of epithelia that expressed the
      highest levels of the variant isoforms were the generative cells, particularly
      the basal cells of stratified squamous epithelium, and of glandular epithelium.
      CD44 variant isoforms were also expressed differentially by leukocytes, with CD44
      9v expressed at very low levels and CD44-6v and 4v virtually absent. However,
      CD44-9v and CD44-6v were the main variants that were transiently upregulated on T
      cells after mitogenic stimulation and on myelomonocytic cell lines by TNF alpha
      and IFN gamma treatment. Some epithelial cell lines could preferentially
      upregulate CD44-6v upon IFN gamma incubation. These results show that CD44
      variant isoforms are expressed much more widely than first appreciated, and that
      expression of the variant isoforms on some cell types can be modulated by
      particular cytokines.

PMID- 7507495
TI  - The involvement of specific anti myelin basic protein antibody-forming cells in
      multiple sclerosis immunopathology.
AB  - Irrespective of the large body of literature on the putative role of antibodies
      in the development of multiple sclerosis (MS), the detection of specific antibody
      forming B cells (AFCs) in the central nervous system (CNS) tissues has not been
      described. In this study we show that autoantigen-specific AFCs can be found in
      CSN tissue sections of MS patients. Applying a newly developed myelin basic
      protein (MBP)-enzyme conjugate technique, we have detected MBP-specific AFCs in
      autopsy periventricular white matter and cerebellum tissue sections of MS
      patients. We demonstrated the presence of MBP-specific AFCs in CNS tissue
      sections in five out of 12 MS patients. No MBP-specific AFCs were detected in CNS
      tissue sections of 11 patients with other neurological diseases, such as
      Parkinson's and Alzheimer's disease, or in brain tissue sections of eight
      deceased persons without neurological diseases. In MS patients, anti-MBP AFCs
      were present in brain tissue sections both with and without plaques. The
      proportion of MBP-specific AFCs in some of the MS patient brain tissues reached
      over 50% of all AFCs. The high relative frequency of the anti-MBP AFCs and their
      localization in periventricular white matter and cerebellum of MS patients only,
      suggests that anti-MBP AFCs represent a cell population, which could play an
      important role in MS immunopathology.

PMID- 7507494
TI  - Isolation of a highly specific ligand for the alpha 5 beta 1 integrin from a
      phage display library.
AB  - Our previous studies showed that the alpha 5 beta 1 integrin selects cysteine
      pair-containing RGD peptides from a phage display library based on a random
      hexapeptide. We have therefore searched for more selective peptides for this
      integrin using a larger phage display library, where heptapeptides are flanked by
      cysteine residues, thus making the inserts potentially cyclic. Most of the phage
      sequences that bound to alpha 5 beta 1 (69 of 125) contained the RGD motif. Some
      of the heptapeptides contained an NGR motif. As the NGR sequence occurs in the
      cell-binding region of the fibronectin molecule, this sequence could contribute
      to the specific recognition of fibronectin by alpha 5 beta 1. Selection for high
      affinity peptides for alpha 5 beta 1 surprisingly yielded a sequence RRETAWA that
      does not bear obvious resemblance to known integrin ligand sequences. The
      synthetic cyclic peptide GACRRETAWACGA (*CRRETAWAC*) was a potent inhibitor of
      alpha 5 beta 1-mediated cell attachment to fibronectin. This peptide is nearly
      specific for the alpha 5 beta 1 integrin, because much higher concentrations were
      needed to inhibit the alpha v beta 1 integrin, and there was no effect on alpha v
      beta 3- and alpha v beta 5-mediated cell attachment to vitronectin. The peptide
      also did not bind to the alpha IIb beta 3 integrin. *CRRETAWAC* appears to
      interact with the same or an overlapping binding site in alpha 5 beta 1 as RGD,
      because cell attachment to *CRRETAWAC* coated on plastic was divalent cation
      dependent and could be blocked by an RGD-containing peptide. These results reveal
      a novel binding specificity in the alpha 5 beta 1 integrin.

PMID- 7507496
TI  - Human myelin basic protein (MBP) epitopes recognized by mouse MBP-selected T cell
      lines from multiple sclerosis patients.
AB  - We investigated whether myelin basic protein (MBP)-reactive T cells from multiple
      sclerosis (MS) patients can recognize mouse MBP since this is an expected
      requirement for the transfer of experimental autoimmune encephalomyelitis (EAE)
      into severe combined immunodeficiency (SCID) mouse-human chimeras. Peripheral
      blood mononuclear cells from 11 MS patients were analyzed for in vitro
      proliferation to mouse MBP. Six patients (55%) responded to mouse MBP at the
      first or second stimulation. Five T cell lines, selected with mouse MBP from five
      MS patients, were analyzed for their proliferation to mouse and human MBP and to
      a panel of synthetic peptides of human MBP. Four of the five lines recognized
      mouse MBP. In vitro proliferation was restricted by MHC class II in one line
      tested for MHC restriction. One of the five lines recognized whole human MBP and
      all five of the lines responded to at least one of the five synthetic peptides
      corresponding to human MBP residues 8-28, 67-90, 84-102, 87-99 or 130-149. These
      results show that MS patient T cells recognize mouse MBP and suggest that
      distinct human MBP epitopes are immunologically cross-reactive with epitopes of
      mouse MBP.

PMID- 7507498
TI  - V delta 1 gene usage, interleukin-2 receptors and adhesion molecules on gamma
      delta+ T cells in inflammatory diseases of the nervous system.
AB  - This study investigates the expression of T cell receptor V delta 1 chain,
      interleukin-2 receptor alpha-chain (CD25) and adhesion molecules ICAM-1 (CD54),
      LFA-1 (CD11a/18) and CD44 on gamma delta+ T cells by three-color flow cytometry
      on cerebrospinal fluid (CSF) and blood cells in patients with multiple sclerosis
      (MS), other inflammatory neurological diseases (OIND) and other neurological
      diseases (OND). Of gamma delta + T cells in CSF and blood, 20-40% belonged to the
      'epithelial' V delta 1 subtype. MS patients had the lowest levels in both CSF and
      blood, but the differences between the patient groups were not significant. The
      activation markers CD25 and CD54 were expressed by only a small proportion of
      gamma delta+ T cells and in a minority of patients. Although the occurrence of
      CD25+ and CD54+ gamma delta+ T cells was somewhat higher in CSF than in blood and
      in inflammatory diseases than in controls, the small numbers of CD25+ and CD54+
      gamma delta+ T cells preclude establishing differences amongst compartments and
      patient groups. The adhesion molecules CD11a/18 and CD44 were constitutively
      expressed on all T cells. Therefore, we compared the relative antigen density per
      cell as measured by the relative fluorescence index (RFI) between CSF and blood,
      between the patient groups and between gamma delta+ and total T cells. The only
      difference encountered was a slightly higher expression of adhesion molecules on
      gamma delta+ compared to total T cells, with preference to MS patients. In
      conclusion, the V delta 1+ subtype of gamma delta+ T cells does not dominate in
      the CSF compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507493
TI  - Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking
      PMC1, a homolog of plasma membrane Ca2+ ATPases.
AB  - Ca2+ ATPases deplete the cytosol of Ca2+ ions and are crucial to cellular Ca2+
      homeostasis. The PMC1 gene of Saccharomyces cerevisiae encodes a vacuole membrane
      protein that is 40% identical to the plasma membrane Ca2+ ATPases (PMCAs) of
      mammalian cells. Mutants lacking PMC1 grow well in standard media, but sequester
      Ca2+ into the vacuole at 20% of the wild-type levels. pmc1 null mutants fail to
      grow in media containing high levels of Ca2+, suggesting a role of PMC1 in Ca2+
      tolerance. The growth inhibitory effect of added Ca2+ requires activation of
      calcineurin, a Ca2+ and calmodulin-dependent protein phosphatase. Mutations in
      calcineurin A or B subunits or the inhibitory compounds FK506 and cyclosporin A
      restore growth of pmc1 mutants in high Ca2+ media. Also, growth is restored by
      recessive mutations that inactivate the high-affinity Ca(2+)-binding sites in
      calmodulin. This mutant calmodulin has apparently lost the ability to activate
      calcineurin in vivo. These results suggest that activation of calcineurin by Ca2+
      and calmodulin can negatively affect yeast growth. A second Ca2+ ATPase homolog
      encoded by the PMR1 gene acts together with PMC1 to prevent lethal activation of
      calcineurin even in standard (low Ca2+) conditions. We propose that these Ca2+
      ATPase homologs are essential in yeast to deplete the cytosol of Ca2+ ions which,
      at elevated concentrations, inhibits yeast growth through inappropriate
      activation of calcineurin.

PMID- 7507497
TI  - Lipopolysaccharide induces substance P in sympathetic ganglia via ganglionic
      interleukin-1 production.
AB  - The immune cytokine interleukin-1 (IL-1) causes a pronounced elevation in
      substance P (SP) immunoreactivity and the mRNA coding for its preprotachykinin
      precursor in cultured superior cervical (sympathetic) ganglia (SCG; Jonakait and
      Schotland, 1990; Freidin and Kessler, 1991; Hart et al., 1991). In this study we
      have investigated the possibility that the SCG can respond to other immune
      stimulators, notably lipopolysaccharide (LPS), a product of bacterial cell walls.
      LPS treatment of cultured SCG resulted in a dose-dependent increase in SP.
      However, LPS did not induce SP in the absence of non-neuronal cells, suggesting
      the necessity of a non-neuronal cell-derived intermediate. Since the LPS
      induction of SP was partially blocked by a specific IL-1 receptor antagonist (IL
      1ra) and since LPS induced approximately an 8-fold increase in mRNA coding for IL
      1 itself, we concluded that IL-1 is at least one of these LPS-induced
      intermediates. TNF-alpha, which also raises SP levels, may be another. IL-6,
      which may also be increased by LPS, does not increase levels of SP. The synthetic
      glucocorticoid hormone dexamethasone (DEX) blocks the LPS induction of SP with a
      Ki approximating 8 x 10(-11) M. The inhibition is due in part to the blockade of
      the LPS induction of ganglionic IL-1 mRNA. Moreover, inhibition of the LPS
      induction of SP by indomethacin implies mediation of the effect through
      prostaglandins. The inhibition by indomethacin suggests a non-monocytic cell
      source since prostaglandins are thought to restrict the LPS induction of
      monocytic IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507499
TI  - Neuropeptide-mediated regulation of hapten-specific IgE responses in mice. II.
      Mechanisms of substance P-mediated isotype-specific suppression of BPO-specific
      IgE antibody-forming cell responses induced in vitro.
AB  - Previous studies in our laboratory have shown that substance P (SP), injected
      into benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) sensitized mice at the
      peak of the benzylpenicilloyl (BPO)-specific IgE response, suppressed these
      responses in isotype-specific fashion within 48 h. These studies also showed that
      SP, but not neurotensin (NT), serotonin (5-HT), somatostatin (SOM) or gastrin,
      suppressed BPO-specific memory IgE antibody-forming cell (AFC) responses induced
      in vitro, also in isotype-specific fashion. To investigate the mechanisms by
      which SP suppressed BPO-specific IgE AFC responses were induced in vitro, these
      responses were induced by culturing spleen cells from BPO-KLH sensitized mice for
      5 days with BPO-KLH with or without whole SP, amino terminal SP (SP 1-4: Arg-Lys
      Pro-Lys), or carboxy terminal SP (SP 8-11: Phe-Gly-Leu-Met). In some experiments,
      the SP receptor antagonist (D-Pro2, D-Phe7, D-Trp9)-SP (D-SP) was included in
      culture. In other experiments anti-interferon monoclonal antibody (anti-IFN gamma
      mAb) was in culture. Whole SP and SP 8-11, but not SP 1-4, suppressed BPO
      specific IgE AFC responses induced in vitro. The suppression obtained was IgE
      isotype-specific and dose-dependent. Inclusion of SP receptor antagonist (D-Pro2,
      D-Phe7, D-Trp9)-SP inhibited suppression of BPO-specific memory IgE AFC responses
      by SP or SP 8-11. The SP-mediated suppression of BPO-specific memory IgE
      responses appeared to involve interferon gamma (IFN gamma).

PMID- 7507500
TI  - Optic neuritis is associated with myelin basic protein and proteolipid protein
      reactive cells producing interferon-gamma, interleukin-4 and transforming growth
      factor-beta.
AB  - Studies on patients with monosymptomatic optic neuritis (ON) should give
      opportunities to identify features typical for early multiple sclerosis (MS).
      There are increased T and B cell responses to the myelin components myelin basic
      protein (MBP) and proteolipid protein (PLP) in both ON and MS, but there is
      little information on the types of cytokines produced by such cells. We describe
      the use of in situ hybridization with complementary DNA oligonucleotide probes to
      detect and enumerate mononuclear cells expressing mRNA for the cytokines
      interferon-gamma (IFN-gamma) which augments cell-mediated immunity; interleukin-4
      (IL-4) which promotes the B cell response; and transforming growth factor beta
      (TGF-beta) that in many cases downregulates immune responses. Expression of these
      cytokines was studied in mononuclear cells from peripheral blood and
      cerebrospinal fluid (CSF) from patients with ON and MS after in vitro exposure to
      MBP and PLP, and in absence of antigen. There were elevated levels of cells that
      in response to MBP and PLP expressed IFN-gamma, IL-4 and TGF-beta mRNA in blood
      and further enriched in CSF in both ON and MS, compared to patients with other
      neurological diseases. The results suggest that IFN-gamma, IL-4 as well as TGF
      beta are involved in both ON and MS, and that the cytokine profile in early MS as
      reflected by ON is not different from that in clinically definite MS.

PMID- 7507501
TI  - Schnitzler's syndrome associated with sensorimotor neuropathy.
AB  - We describe a patient with chronic urticaria in association with monoclonal IgM
      gammopathy (Schnitzler's syndrome). Seven years after the onset of the cutaneous
      lesions sensorimotor neuropathy developed. Myelin-associated glycoprotein was
      detected in the patient's serum. High doses of corticosteroids improved the skin
      condition but failed to prevent the neuropathy. Six months of treatment with
      immunoglobulins was without benefit.

PMID- 7507503
TI  - Child and adolescent psychopathology research: problems and prospects for the
      1990s.
AB  - In November 1990 the National Institute of Mental Health (NIMH) convened a
      special conference of over 100 scientists and leaders to outline specific
      strategies and research initiatives that should be developed to implement the
      recently released National Plan for Research on Child and Adolescent Mental
      Disorders. Participants included journal editors, educators from psychology and
      psychiatry, representatives from private foundations, and leaders of research
      program areas in public funding agencies. Critical knowledge gaps were identified
      in five areas of child and adolescent psychopathology, including depression,
      attention deficit hyperactivity disorder, conduct disorder, the anxiety
      disorders, and the developmental disorders. For each of these areas, special
      emphasis was placed on developing new ideas and obtaining critical input from
      other areas of investigation. This report summarizes the identified research gaps
      and recommends research initiatives to implement the National Plan, as outlined
      by the conference participants.

PMID- 7507502
TI  - Possible mechanisms of organophosphorus and carbamate insecticide resistance in
      German cockroaches (Dictyoptera: Blattelidae) from different geographical areas.
AB  - The resistance status of 14 strains of Blattella germanica (L.) from four
      countries was determined for chlorpyrifos and propoxur compared with a standard
      reference susceptible strain. Thirteen strains were resistant to chlorpyrifos; 12
      strains were resistant to propoxur. Resistance ratios for chlorpyrifos ranged
      from 8- to 462-fold at LC90; for propoxur, resistance ratios ranged from 4- to 46
      fold. One cockroach strain from Denmark had negative cross-resistance to
      chlorpyrifos, and one strain from the United States had negative cross-resistance
      to propoxur. Slopes of probit regressions indicated that all resistant strains
      were heterogeneous for resistance to both chlorpyrifos and propoxur. Synergist
      studies with piperonyl butoxide indicated that multifunction mono-oxidases are
      probably involved in resistance to chlorpyrifos in six strains and in resistance
      to propoxur in seven strains. Esterase activity was elevated in 10 strains; of
      these strains, two had only slightly elevated esterase activity as measured with
      the substrates 1- and 2-naphthyl acetate. The remainder had higher levels of
      elevated esterase activity to both substrates. Strains with elevated esterase
      activity were resistant to a broad spectrum of organophosphates, pyrethroids, or
      both. Increased levels of glutathione S-transferase activity were found in four
      strains. Another two strains had a low frequency (1%) of individuals with high
      glutathione S-transferase activity. Elevated glutathione S-transferase activity
      was not correlated with the observed levels of organophosphate or carbamate
      resistance. One strain from Dubai had an altered acetylcholinesterase-based
      mechanism that conferred broad-spectrum resistance to a range of organophosphates
      and carbamates.

PMID- 7507504
TI  - Frequency of predischarge ventricular arrhythmias in postmyocardial infarction
      patients depends on residual left ventricular pump performance and is independent
      of the occurrence of acute reperfusion. The GISSI-2 Investigators.
AB  - OBJECTIVES: To test whether acute reperfusion of the infarct-related vessel after
      an acute myocardial infarction is associated with a subsequent reduction in
      spontaneous ventricular arrhythmias that is independent of ventricular ejection
      fraction, 1,944 patients from the GISSI-2 study population were studied. The
      patients were selected on the basis of a first myocardial infarction and the
      availability of two-dimensional echocardiographic ejection fraction and data on
      the number of premature ventricular contractions per hour on Holter monitoring.
      BACKGROUND: It has been suggested that postthrombolytic reperfusion of the
      culprit vessel may be associated with an increased electrical stability of the
      infarcted heart, irrespective of its residual pump performance. METHODS: The
      predischarge relation between ejection fraction and number of premature
      ventricular contractions per hour was plotted according to the occurrence (1,309
      patients) or not (635 patients) of acute reperfusion, identified noninvasively
      according to the modifications of the ST segment in serial electrocardiograms
      obtained in the first 24 h after infarction. RESULTS: The frequency of premature
      ventricular contractions increased in a linear fashion with decreasing ejection
      fraction in both cohorts (p < 0.005 and p < 0.0001); however, there was no
      significant difference between the slopes and the intercepts of the two
      regression lines, so that the relation between ejection fraction and number of
      premature ventricular contractions per hour could be adequately described by a
      single equation: y (number of premature ventricular contractions) = 33.0-0.42x
      (ejection fraction) (r = -0.107, p < 0.0001). The results were the same even when
      differences between group characteristics were accounted for in a multiple
      regression model. CONCLUSIONS: It is concluded that 1) the number of premature
      ventricular contractions per hour after an acute myocardial infarction is
      dependent in a linear, inverse fashion on the residual ventricular ejection
      fraction, and 2) this relation is independent of the occurrence of reperfusion in
      the acute phase of infarction.

PMID- 7507505
TI  - [Epidemiological study on nosocomial infection of Pseudomonas cepacia by plasmid
      analyses].
AB  - In order to clarify the usefulness of plasmid analyses in epidemiological study,
      plasmid DNA profiles, restriction fragment patterns of chromosomal DNA analysed
      by pulsed-field gel electrophoresis (PFGE), and patterns of extracellular
      products were performed in twenty-four nosocomial strains of Pseudomonas cepacia
      isolated at the Kagawa Medical School Hospital. Fifteen strains were obtained
      from 15 patients admitted in A ward, three strains were obtained from nebulizer
      devices used in A ward, 5 strains were obtained from 5 patients admitted in B
      ward, and 1 strain was obtained from a patient admitted in C ward. Three
      different patterns which differed from ward to ward were clearly distinguished by
      PFGE patterns and patterns of extracellular products. On the other hand, plasmid
      DNA profiles were different in some strains obtained from B ward. These results
      suggested that plasmid analyses combined with other typing methods are useful in
      more precise epidemiological analysis on nosocomial infection of P. cepacia.

PMID- 7507506
TI  - Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by
      interacting with an oxygen modified solid phase surface.
AB  - Anticardiolipin antibodies (aCL) derived from the sera of individuals exhibiting
      the antiphospholipid syndrome (APS) directly bind to beta 2-glycoprotein I (beta
      2-GPI), which is adsorbed to an oxidized polystyrene surface. Oxygen atoms were
      introduced on a polystyrene surface by irradiation with electron or gamma-ray
      radiation. X-ray photoelectron spectroscopy revealed the irradiated surfaces were
      oxidized to generate C-O and C = O moieties. aCL derived from either APS patients
      or (NZW x BXSB)F1 mice bound to beta 2-GPI coated on the irradiated plates,
      depending on the radiation dose. Antibody binding to beta 2-GPI on the irradiated
      plates was competitively inhibited by simultaneous addition of cardiolipin (CL)
      coated latex beads mixed together with beta 2-GPI but were unaffected by addition
      of excess beta 2-GPI, CL micelles, or CL-coated latex beads alone. There was a
      high correlation between binding values of aCL in sera from 40 APS patients
      obtained by the anti-beta 2-GPI enzyme-linked immunosorbent assay (ELISA) using
      the irradiated plates and those by the beta 2-GPI-dependent aCL ELISA. Therefore,
      aCL have specificity for an epitope on beta 2-GPI. This epitope is expressed by a
      conformational change occurring when beta 2-GPI interacts with an oxygen
      substituted solid phase surface.

PMID- 7507507
TI  - NF-kappa B and I kappa B alpha: an inducible regulatory system in endothelial
      activation.
AB  - Structural analysis of the promoters of several endothelial genes induced at
      sites of inflammatory or immune responses reveals binding sites for the
      transcription factor nuclear factor kappa B (NF-kappa B). Endothelial cells
      express transcripts encoding the p50/p105 and p65 components of NF-kappa B and
      the rel-related proto-oncogene c-rel; steady state levels of these transcripts
      are transiently increased by tumor necrosis factor alpha (TNF-alpha). Western
      blotting revealed that stimulation of endothelial cells with TNF-alpha resulted
      in nuclear accumulation of the p50 and p65 components of NF-kappa B. Ultraviolet
      crosslinking and immunoprecipitation demonstrated binding of the p50 and p65
      components of NF-kappa B to the E-selectin kappa B site. Endothelial cells
      express an inhibitor of NF-kappa B activation, I kappa B-alpha (MAD-3). Protein
      levels of this inhibitor fall rapidly after TNF-alpha stimulation. In parallel,
      p50 and p65 accumulate in the nucleus and RNA transcript levels for I kappa B
      alpha are dramatically upregulated. Recombinant p65 stimulates expression of E
      selectin promoter-reporter constructs. I kappa B-alpha inhibits p65 or TNF-alpha
      stimulated E-selectin promoter-reporter gene expression in transfected
      endothelial cells. The NF-kappa B and I kappa B-alpha system may be an inducible
      regulatory mechanism in endothelial activation.

PMID- 7507508
TI  - Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated
      tumor immunity.
AB  - A costimulatory signal through B7 to its counter-receptor CD28 on T cells
      enhances T cell activation. We have generated recombinant retroviruses containing
      cDNA for murine B7 and transduced a panel of murine tumor lines with varying
      immunogenicity to study the effect of B7 costimulation on antitumor immunity. In
      contrast to the progressive outgrowth of all wild-type (B7-) tumors in
      unimmunized syngeneic mice, four immunogenic tumors, lymphoma RMA, EL4,
      mastocytoma P815, and melanoma E6B2, regressed completely when transduced with
      the B7 gene. In contrast, four nonimmunogenic tumors, sarcomas MCA101, MCA102,
      and Ag104, and melanoma B16, remained tumorigenic after transduction of the B7
      gene. Immunization with B7-transduced immunogenic tumors enhanced protective
      immunity and increased specific cytotoxic T lymphocyte (CTL) activity against the
      respective wild-type tumors as compared to immunization with nontransduced or
      mock-transduced tumors. Moreover, cocultivation of CTL with B7-transduced EL4
      cells augmented the specificity of tumor-reactive CTL in long-term cultures.
      Treatment by injection of B7-transduced tumor cells cured 60% of mice with
      established wild-type EL4 lymphoma. In contrast, immunization with nonimmunogenic
      tumors transduced with B7 did not provide protective immunity and did not
      increase specific CTL activity. Our results show that tumor immunogenicity is
      critical to the outcome of costimulation of T cell-mediated tumor immunity by B7.

PMID- 7507509
TI  - The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune
      disease: increased nitric oxide production and nitric oxide synthase expression
      in MRL-lpr/lpr mice, and reduction of spontaneous glomerulonephritis and
      arthritis by orally administered NG-monomethyl-L-arginine.
AB  - MRL-lpr/lpr mice spontaneously develop various manifestations of autoimmunity
      including an inflammatory arthropathy and immune complex glomerulonephritis. This
      study examines the role of nitric oxide, a molecule with proinflammatory actions,
      in the pathogenesis of MRL-lpr/lpr autoimmune disease. MRL-lpr/lpr mice excreted
      more urinary nitrite/nitrate (an in vivo marker of nitric oxide production) than
      did mice of normal strains and MRL-(+/+) and B6-lpr/lpr congenic strains. In
      addition, MRL-lpr/lpr peritoneal macrophages had an enhanced capacity to produce
      nitric oxide in vitro as well as increased nitric oxide synthase activity, and
      certain tissues from MRL-lpr/lpr mice had increased expression of inducible
      nitric oxide synthase (NOS) mRNA and increased amounts of material immunoreactive
      for inducible NOS. Oral administration of NG-monomethyl-L-arginine, a nitric
      oxide synthase inhibitor, prevented the development of glomerulonephritis and
      reduced the intensity of inflammatory arthritis in MRL-lpr/lpr mice. By using
      interspecific backcross mice, the gene for inducible NOS (Nosi) was mapped to
      mouse chromosome 11. This chromosomal localization was different from those loci
      that we have previously demonstrated to be linked to enhanced susceptibility to
      renal disease in an MRL-lpr/lpr cross. However, the chromosomal location of the
      NOS gene was consistent with an insulin-dependent diabetes locus identified in an
      analysis of nonobese diabetic (NOD) mice. These results suggest that elevated
      nitric oxide production could be important in the pathogenesis of autoimmunity,
      and that treatments to block the production of nitric oxide or block its effects
      might be valuable therapeutically.

PMID- 7507510
TI  - Signal transduction via CD40 involves activation of lyn kinase and
      phosphatidylinositol-3-kinase, and phosphorylation of phospholipase C gamma 2.
AB  - CD40 is a 50-kD glycoprotein that plays an important role in B cell survival,
      memory, and immunoglobulin isotype switch. Engagement of the CD40 antigen by
      monoclonal antibodies (mAbs) results in increased protein tyrosine kinase (PTK)
      activity, which plays an important role in mediating the biologic effects of
      CD40. We demonstrate, using an in situ phosphorylation technique, that CD40 cross
      linking by the anti-CD40 mAb 626.1 resulted within 1 min in increased
      phosphorylation of the src type kinase, lyn, in Daudi B cell lines and remained
      sustained for up to 20 min. The activity of lyn kinase, as measured by immune
      complex kinase assay, was also increased after CD40 engagement, with similar
      kinetics. In contrast, the phosphorylation and activity of fyn, fgr, and lck
      kinases demonstrated minimal changes following stimulation of Daudi cells with
      mAb 626.1 over this same time period. CD40 engagement also resulted in
      phosphorylation of phospholipase C gamma 2 of phosphatidylinositol (PLC gamma 2)
      and phosphatidylinositol (PI)-3-kinase. Phosphorylation of PI-3-kinase was shown
      to be associated with an increase in its enzymatic activity. These results
      suggest that lyn plays an important role in CD40-mediated PTK activation and
      identify PLC gamma 2 and PI-3-kinase targets for CD40-mediated phosphorylation,
      suggesting a role for these two enzymes in CD40 signal transduction.

PMID- 7507511
TI  - The combination of anti-B7 monoclonal antibody and cyclosporin A induces
      alloantigen-specific anergy during a primary mixed lymphocyte reaction.
AB  - Interaction of CD28/CTLA-4 on T cells with B7 on antigen-presenting cells
      constitutes an important costimulatory signal for T cells and is responsible for
      cyclosporin A-resistant interleukin 2 (IL-2) gene expression and potentially also
      for prevention of anergy induction after T cell receptor triggering. In this
      paper, we demonstrate that addition of a monoclonal antibody to B7, which blocks
      B7-CD28/CTLA-4 interaction, and of cyclosporin A together, but not separately, to
      a primary mixed lymphocyte reaction of freshly isolated human T cells towards a
      human B cell line, induces nonresponsiveness of alloantigen-specific cytotoxic T
      lymphocyte precursors, whereas reactivity to a third party stimulator is intact.
      Nonresponsiveness could be reversed by culture in IL-2, indicating that anergy,
      and not clonal deletion, is responsible for this phenomenon. Our finding opens
      important perspectives for the development of new therapeutic strategies in
      transplantation.

PMID- 7507513
TI  - Expression of tyrosine hydroxylase gene in cultured hypothalamic cells: roles of
      protein kinase A and C.
AB  - In hypothalamic cells cultured in serum-free medium, the quantity of tyrosine
      hydroxylase mRNA increases after treatment with an activator of the protein
      kinase A pathway (8-bromoadenosine cyclic AMP, 3-isobutyl-1-methylxanthine, or
      forskolin) or an activator of protein kinase C (12-O-tetradecanoylphorbol 13
      acetate or sn-1,2-diacylglycerol). The tyrosine hydroxylase mRNA level decreases
      in the cells after inhibition of protein kinase C with calphostin C or after
      depletion of protein kinase C by extended phorbol ester treatment. These data
      suggest that both protein kinase pathways regulate tyrosine hydroxylase gene
      expression in hypothalamic cells. As simultaneous activation of both pathways has
      less than an additive effect on the tyrosine hydroxylase mRNA level, they appear
      to be interrelated. Compared with the rapid and dramatic increase of the tyrosine
      hydroxylase mRNA level in pheochromocytoma cells, activation of the protein
      kinase A or protein kinase C pathway in the cultured hypothalamic cells induces
      slow changes of a small magnitude in the amount of tyrosine hydroxylase mRNA. The
      slow regulation of tyrosine hydroxylase gene expression in hypothalamic
      dopaminergic neurons corresponds to the relatively high stability of tyrosine
      hydroxylase mRNA (half-life = 14 +/- 1 h) in these cells.

PMID- 7507514
TI  - Increased production of paired helical filament epitopes in a cell culture system
      reduces the turnover of tau.
AB  - To investigate the regulation of posttranslational modifications of tau that
      might be pertinent to the production of the paired helical filament (PHF) of
      Alzheimer's disease, we incubated human neuroblastoma cells with the protein
      phosphatase inhibitor okadaic acid. This treatment results in increased
      immunoreactivity of tau with the monoclonal antibodies Alz-50, PHF-1, T3P, and
      NP8, a reduction in Tau-1 immunoreactivity, and an elevation in apparent
      molecular weight of tau. Moreover, our data demonstrate that accumulation of
      phosphates in tau leads to a decrease in the turnover rate of tau in the
      neuroblastoma cells. It is suggested that similar build-up of hyperphosphorylated
      tau in the neuronal perikarya may represent an early event in PHF formation. The
      present system facilitates the investigation of regulatory mechanisms governing
      the occurrence of PHF epitopes, their effects on neuronal cell metabolism, and
      possible pharmacological intervention.

PMID- 7507512
TI  - Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil
      activating chemokine.
AB  - CC chemokines constitute a novel class of cytokines that attract and activate
      monocytes and lymphocytes, as well as basophil and eosinophil leukocytes, with
      distinct target cell profiles, and are believed to be involved in the regulation
      of different types of inflammation. The action of the recently identified
      monocyte chemotactic protein 3 (MCP-3) on human basophil and eosinophil function
      was studied and compared with that of other CC chemokines. In basophils, MCP-3,
      MCP-1, RANTES, and macrophage inflammatory protein (MIP)-1 alpha all induced
      cytosolic-free calcium concentration ([Ca2+]i) changes and, with different
      efficacies, chemotaxis (RANTES = MCP-3 >> MCP-1 > MIP-1 alpha), histamine release
      (MCP-1 = MCP-3 >> RANTES > MIP-1 alpha), and leukotriene C4 formation, after IL-3
      pretreatment (MCP-1 = MCP-3 >> RANTES > MIP-1 alpha). Thus, MCP-3 was as
      effective as MCP-1 as an inducer of mediator release, and as effective as RANTES
      as a stimulus of basophil migration. In contrast to MCP-1, MCP-3 was also a
      stimulus for eosinophils, and induced [Ca2+]i changes and chemotaxis as
      effectively as RANTES, which is the most potent chemotactic cytokine for these
      cells. Desensitization of the transient changes in [Ca2+]i was used to assess
      receptor usage. In basophils, stimulation with MCP-3 prevented responsiveness to
      MCP-1 and RANTES, but not to MIP-1 alpha. No single CC chemokine (except for MCP
      3 itself) affected the response to MCP-3, however, which was prevented only when
      the cells were prestimulated with both MCP-1 and RANTES. In eosinophils, by
      contrast, cross-desensitization between RANTES and MCP-3 was obtained. RANTES and
      to a lesser extent MCP-3 also desensitized eosinophils toward MIP-1 alpha. The
      desensitization data suggest the existence of three chemokine receptors: (a) a
      MCP-1 receptor expressed on basophils but not eosinophils that is activated by
      MCP-1 and MCP-3; (b) a RANTES receptor in basophils and eosinophils that is
      activated by RANTES and MCP-3; and (c) a MIP-1 alpha receptor that is activated
      by MIP-1 alpha, RANTES and, more weakly, by MCP-3. This study shows that MCP-3
      combines the properties of RANTES, a powerful chemoattractant, and MCP-1, a
      highly effective stimulus of mediator release, and thus has a particularly broad
      range of activities toward both human basophil and eosinophil leukocytes.

PMID- 7507516
TI  - Antibodies to myelin/oligodendrocyte-specific protein and myelin/oligodendrocyte
      glycoprotein signal distinct changes in the organization of cultured
      oligodendroglial membrane sheets.
AB  - Cultured murine oligodendrocytes elaborate extensive membrane sheets that, unlike
      multilamellar myelin in vivo, allow the study of interactions between myelin
      proteins and cytoskeletal elements. This article describes the events that occur
      due to the interaction of specific antibodies with their respective antigens,
      myelin/oligodendrocyte-specific protein (MOSP) and myelin/oligodendrocyte
      glycoprotein (MOG), which are expressed uniquely by oligodendrocytes. After
      antibody binding, surface anti-MOSP:MOSP complexes redistribute over those
      cytoplasmic microtubular veins that have 2',3'-cyclic nucleotide 3'
      phosphohydrolase colocalized along them. In contrast, surface anti-MOG-MOG
      complexes redistribute over internal myelin basic protein domains. Long-term anti
      MOSP IgM exposure results in an apparent increase in number as well as thickness
      of microtubular structures in oligodendrocyte membrane sheets, whereas long-term
      anti-MOG exposure causes depolymerization of microtubular veins in membrane
      sheets. These data suggest that antibody binding to these two surface proteins
      elicits signals that have opposite effects on the cytoskeleton in
      oligodendroglial membrane sheets. Thus, it is possible that signals transduced
      via antibody binding may contribute to the pathogenesis of diseases affecting CNS
      myelin.

PMID- 7507515
TI  - Polyclonal antibodies directed against an epitope specific for the alpha 4
      subunit of GABAA receptors identify a 67-kDa protein in rat brain membranes.
AB  - Polyclonal antibodies were raised to the C-terminal part of the gamma
      aminobutyric acidA (GABAA) receptor alpha 4-subunit. These anti-peptide alpha 4
      (517-523) antibodies specifically identified a protein with apparent molecular
      mass 67 kDa in rat brain membranes. This protein was enriched by immunoaffinity
      chromatography of brain membrane extracts on Affigel 10 coupled to the anti
      peptide alpha 4 (517-523) antibodies and could then be identified by the anti
      alpha 4-antibodies as well as by the GABAA receptor subunit-specific monoclonal
      antibody bd-28. This appears to indicate that the 67-kDa protein is the alpha 4
      subunit of GABAA receptors. Intact GABAA receptors appeared to be retained by the
      immunoaffinity column because other GABAA receptor subunit proteins like the beta
      2/beta 3-subunits and the gamma 2-subunit were detected in the immunoaffinity
      column eluate. Furthermore, in addition to the 67-kDa protein, a 51-kDa protein
      could be detected by the antibody bd-28 and the anti-peptide alpha 4 (517-523)
      antibody in the immunoaffinity column eluate. A protein with similar apparent
      molecular mass was identified by the alpha 1-subunit-specific anti-peptide alpha
      1 (1-9) antibody. In contrast to the alpha 1-subunit, the 51-kDa protein
      identified by the anti-alpha 4 antibody could not be deglycosylated by N
      Glycanase. The identity of the 51-kDa protein identified by the anti-alpha 4
      antibodies thus must be further investigated.

PMID- 7507517
TI  - Nitric oxide synthase expression in glial cells: suppression by tyrosine kinase
      inhibitors.
AB  - Rat brain glial cells have the capacity to express a calcium-independent form of
      nitric oxide synthase (iNOS). To test if iNOS induction required tyrosine kinase
      activity, we made use of genistein, a selective inhibitor of tyrosine kinases. In
      both primary astrocyte cultures and C6 glioma cells, the presence of genistein
      prevented both lipopolysaccharide- and cytokine-induced NOS activity in a dose
      dependent manner. The presence of tyrphostin-25 (10 microM), which is highly
      specific for tyrosine kinases, also blocked iNOS induction. Additional
      characterization showed that genistein blocked iNOS induction in a dose-dependent
      manner (IC50 of approximately 40 microM), that the continuous presence of
      genistein was not necessary to observe inhibition, and that preincubation with
      genistein led to higher levels of inhibition than the simultaneous addition of
      genistein and inducers. The decrease in iNOS activity due to genistein was
      accompanied by a decrease in iNOS mRNA level as detected by a specific PCR assay.
      These results indicate that induction of astroglial iNOS expression requires
      tyrosine kinase activity.

PMID- 7507518
TI  - Quaternary structure of the native GABAA receptor determined by electron
      microscopic image analysis.
AB  - In the transmitter-gated ion channel class of receptors, the members of which are
      all believed to be heterooligomers, the number and arrangement of the subunits
      are only known with any certainty for the nicotinic acetylcholine receptor from
      Torpedo electric fish. That receptor has been shown to possess a pentameric
      rosette structure, with five homologous subunits (alpha 2, beta gamma delta)
      arranged to enclose the central ion channel. The data were obtained by electron
      image analysis of two-dimensional receptor arrays, which form as a consequence of
      that receptor's exceptionally high abundance in the Torpedo membranes and are
      therefore not attainable for other receptors. We have applied another direct
      approach to determine the quaternary structure of native ionotropic GABA
      receptors. We have purified those receptors from porcine brain cortex and
      analysed the rotational symmetry of isolated receptors visualized by electron
      microscopy. The results show the receptor to have a pentameric structure with a
      central water-filled pore, which can now be said to be characteristic of the
      entire superfamily.

PMID- 7507519
TI  - NMDA receptor-mediated components of miniature excitatory synaptic currents in
      developing rat neocortex.
AB  - 1. In vitro slices of frontal neocortex were prepared from rat pups at various
      ages after birth: postnatal days (PN) 3-5, 6-8, and 9-14. Using whole-cell patch
      clamp techniques, both spontaneous and evoked excitatory postsynaptic currents
      (EPSCs) were recorded from voltage-clamped layer II-III pyramidal neurons.
      Developmental changes in EPSCs were examined. 2. Four properties of miniature
      EPSCs (mEPSCs) were studied: rise time, amplitude, decay time constant (tau), and
      frequency. These parameters were not tetrodotoxin sensitive and did not exhibit
      significant developmental changes during the first two postnatal weeks. 3. mEPSCs
      occurred approximately every 2-3 s and had peak amplitudes of 25-30 pA. Within
      each age group, certain parameters of mEPSCs were voltage dependent. mEPSC rise
      time and decay tau were significantly increased at depolarized potentials (-30 to
      -45 mV) relative to hyperpolarized (-75 to -90 mV) or resting membrane potential
      (RMP) (-60 to -70 mV). 4. At threshold stimulation intensity, EPSCs were evoked
      in an "all-or-none" manner. The amplitude and decay tau of evoked unitary EPSCs
      and mEPSCs were not significantly different. As stimulation intensity was
      increased, a late EPSC component appeared that was not seen in mEPSCs. At
      suprathreshold stimulus intensities, EPSC duration was significantly longer in PN
      3-5 than in PN 9-14 neurons. 5. The N-methyl-D-aspartate (NMDA) receptor
      antagonist D(-)2-amino-5-phosphonovaleric acid (APV, 10 microM) significantly
      decreased mEPSC decay tau and frequency only at depolarized membrane potentials.
      Likewise, EPSCs were depressed by APV to a greater extent at depolarized
      potentials, and the depression was mainly of the late component. mEPSCs recorded
      at RMP were blocked by the non-NMDA receptor antagonist 6-cyano-7
      nitroquinoxaline- 2,3-dione (5 microM). 6. Removal of extracellular Mg2+
      reversibly increased the decay tau of mEPSCs at RMP but not at depolarized
      membrane potentials. The decay tau and duration of evoked EPSCs were also
      increased in zero Mg2+. These effects were reversible with application of APV.
      All effects of zero Mg2+ on mEPSCs and EPSCs were observed as early as PN 3-5. 7.
      These results indicate that the basic kinetic properties of mEPSCs are present by
      PN 3-5 and do not change significantly over the first two postnatal weeks. NMDA
      receptor activation contributes to mEPSCs and sensitivity to Mg2+ appears as
      early as PN 3-5. Unitary EPSCs resemble mEPSCs, but a late NMDA receptor-mediated
      component appears in EPSCs as stimulus intensity is increased.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7507520
TI  - Expression of voltage-activated ion channels by astrocytes and oligodendrocytes
      in the hippocampal slice.
AB  - 1. Using patch-clamp recordings, expression of voltage-activated ion channels by
      identified glial cells in situ was studied in hippocampal slices derived from 5-
      to 24-day-old rats. Glial cells were filled with Lucifer yellow during recording,
      and were identified by staining for glial fibrillary acidic protein (GFAP). Of
      105 cells presumed to be glial cells from which recordings were obtained, 40 were
      identified as astrocytes and 22 as oligodendrocytes. 2. Astrocytes in the
      hippocampal slice express three types of K+ current, singly or in combination:
      delayed rectifying currents (Kd), transient "A"-type currents (Ka) and inward
      rectifying currents (Kir). Kd-like currents were observed in 88% of astrocytes
      recorded; these currents activated rapidly with a threshold of -40 mV and did not
      inactivate during a 10- to 30-ms pulse. A-type transient K+ currents were
      identified in 43% of astrocytes and required a negative holding potential (-110
      mV) for activation. These activated at about -50 mV, and their time constant of
      inactivation was close to 10 ms. In 20% of astrocytes recorded in slices from
      animals > 7 days old, inwardly rectifying K+ currents were observed in addition
      to Kd or Ka. 3. Voltage-activated Na+ currents were observed in 11 of the 105
      cells, and 5 of these were identified as astrocytes by GFAP staining. These were
      located in either stratum oriens or close to the granule cell layer in CA3. Na+
      current densities ranged from 1.5 to 90 pA/pF. Voltage steps more positive than 
      40 mV were required for activation, peaks were close to -10 mV, and time to peak
      was between 300 and 800 microseconds. Extrapolated current reversal potentials
      were close to the theoretical Na+ equilibrium potential. 4. Spontaneous action
      potentials were never observed in any of the hippocampal astrocytes recorded,
      including those astrocytes that expressed Na+ currents. Additionally, action
      potentials could not be induced by current injections. By contrast, 26
      hippocampal neurons recorded in the same slices showed both spontaneous and
      elicited action potentials as well as synaptic currents. 5. Oligodendrocytes,
      identified by lack of GFAP staining and cell morphology, had resting potentials
      ranging between -25 and -82 mV in 5 mM KCl. In approximately 50% of
      oligodendrocytes, time-dependent currents were not observed and only time
      independent currents with linear current-voltage curves were recorded. In the
      remaining 50% of oligodendrocytes, time- and voltage-dependent K+ currents
      characterized by inward rectification were present.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7507521
TI  - Effects of aging on the intrinsic membrane properties of medial NTS neurons of
      Fischer-344 rats.
AB  - 1. Recent studies have demonstrated that the arterial baroreflex is imparied with
      aging and have implicated central components of the baroreflex arc in this
      autonomic dysfunction. Neurons in the medial portion of the nucleus tractus
      solitarius (mNTS) receive a major input from the arterial baroreceptors. The
      present study was undertaken to characterize the intrinsic membrane properties of
      mNTS neurons in young rats and to test the hypothesis that these properties are
      altered with aging. An in vitro brain stem slice preparation was used to record
      intracellularly from mNTS neurons; passive membrane properties, action potential
      characteristics, and repetitive firing properties were examined and compared. 2.
      Neurons in the mNTS of young (3-5 mo old) Fischer-344 rats (F-344; n = 35) had a
      resting membrane potential of -57 +/- 6.9 mV (mean +/- SD), a membrane time
      constant of 18 +/- 9.0 ms, and an input resistance of 110 +/- 60 m omega. Action
      potential amplitude was 81 +/- 7.5 mV with a duration at half-height of 0.83 +/-
      0.15 ms. The spontaneous firing rate in 24 cells was 4.3 +/- 2.9 Hz. The
      amplitude and duration of the action potential afterhyperpolarization (AHP) were
      6.6 +/- 3.0 mV and 64 +/- 34 ms, respectively. All neurons expressed spike
      frequency adaptation, action potential AHP, and posttetanic hyperpolarization.
      Delayed excitation and postinhibitory rebound were present in 34 and 14% of
      neurons tested, respectively. Neurons from adult (10-12 mo old) F-344 rats (n =
      34) were similar to the young F-344 rats with respect to all of these variables.
      3. Neurons from aged (21-24 mo old) F-344 (n = 32) were similar to those from
      young and adult rats, but there were two potentially important differences: the
      mean input resistance of the aged neurons was higher (170 +/- 150 M omega), with
      a larger proportion (46% of aged neurons vs. 20% of young neurons and 21% of
      adult neurons) having input resistances > 150 M omega; and there was a tendency
      for a smaller percentage of aged neurons (16% of aged neurons vs. 34% of young
      neurons and 29% of adult neurons) to express delayed excitation. 4. The potential
      significance of a high input resistance was tested by comparing the steady-state
      current-voltage (I-V) relationships and the frequency-current (f-I) relationships
      among low-resistance (1-100 M omega), medium-resistance (101-200 M
      omega).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7507522
TI  - Anisotropic and heterogeneous diffusion in the turtle cerebellum: implications
      for volume transmission.
AB  - 1. Measurements of extracellular diffusion properties were made in three
      orthogonal axes of the molecular and granular layers of the isolated turtle
      cerebellum with the use of iontophoresis of tetramethylammonium (TMA+) combined
      with ion-selective microelectrodes. 2. Diffusion in the extracellular space of
      the molecular layer was anisotropic, that is, there was a different value for the
      tortuosity factor, lambda i, associated with each axis of that layer. The x- and
      y-axes lay in the plane parallel to the pial surface of this lissencephalic
      cerebellum with the x-axis in the direction of the parallel fibers. The z-axis
      was perpendicular this plane. The tortuosity values were lambda x = 1.44 +/-
      0.01, lambda y = 1.95 +/- 0.02, and lambda z = 1.58 +/- 0.01 (mean +/- SE). By
      contrast, the granular layer was isotropic with a single tortuosity value, lambda
      Gr = 1.77 +/- 0.01. 3. These data confirm the applicability of appropriately
      extended Fickian equations to describe diffusion in anisotropic porous media,
      including brain tissue. 4. Heterogeneity between the molecular and granular layer
      was revealed by a striking difference in extracellular volume fraction, alpha,
      for each layer. In the molecular layer alpha = 0.31 +/- 0.01, whereas in the
      granular layer alpha = 0.22 +/- 0.01. 5. Volume fraction and tortuosity affected
      the time course and amplitude of extracellular TMA+ concentration after
      iontophoresis. This was modeled by the use of the average parameters determined
      experimentally, and the nonspherical pattern of diffusion in the molecular layer
      was compared with the spherical distribution in the granular layer and agarose
      gel by computing isoconcentration ellipsoids. 6. One functional consequence of
      these results was demonstrated by measuring local changes in [K+]o and [Ca2+]o
      after microiontophoresis of a cerebellar transmitter, glutamate. The ratios of
      ion shifts in the x- and y-axes in the granular layer were close to unity, with a
      ratio of 1.04 +/- 0.08 for the rise in [K+]o and 1.03 +/- 0.17 for the decrease
      in [Ca2+]o. In contrast, ion shifts in the molecular layer had an x:y ratio of
      1.44 +/- 0.14 for the rise in [K+]o and 2.10 +/- 0.42 for the decrease in
      [Ca2+]o. 7. These data demonstrate that the structure of cellular aggregates can
      channel the migration of substances in the extracellular microenvironment, and
      this could be a mechanism for volume transmission of chemical signals. For
      example, the preferred diffusion direction of glutamate along the parallel fibers
      would help constrain an incoming excitatory stimulus to stay "on-beam."

PMID- 7507523
TI  - Hyperpolarization-activated currents in neurons of the rat basolateral amygdala.
AB  - 1. A single microelectrode was used to obtain current-clamp or voltage-clamp
      recordings from two neuronal cell types (pyramidal and late-firing neurons) in
      the basolateral nucleus of the amygdala (BLA) in slices of the rat ventral
      forebrain. Conductances activated by hyperpolarizing voltage steps from a holding
      potential of -70 mV were identified and their sensitivity to muscarinic
      modulation was determined using bath superfusion of carbachol. 2. Unclamped
      pyramidal neurons exhibited anomalous rectification, seen as a slowly developing
      depolarizing sag in the electronic potential in response to a hyperpolarizing
      current pulse. 3. Stepping voltage-clamped pyramidal neurons to command
      potentials of between -70 and -100 mV activated a slowly developing inward
      current (ISlow) that followed a single exponential time course. Larger
      hyperpolarizing voltage steps evoked a rapidly developing inward current (IFast)
      that preceded the development of ISlow. 4. The ISlow component reversed at a
      level positive to the -70 mV holding potential. Its rate of activation
      accelerated as the hyperpolarizing voltage step was made more negative. The
      threshold for activation of the conductance underlying ISlow was approximately 
      60 mV, with half-activation occurring at -90 mV. 5. Extracellular Cs+ (2 mM)
      blocked ISlow and eliminated anomalous rectification in unclamped pyramidal
      neurons. The inhibition of ISlow by Cs+ was also associated with membrane
      hyperpolarization and reduction of the medium afterhyperpolarization. ISlow was
      unaffected by extracellular Ba2+ (100 microM). The properties of this current
      appeared similar to that of the mixed cationic H-current previously identified in
      other neurons. 6. In comparison with pyramidal cells, unclamped late-firing
      neurons displayed a lesser but more rapidly developing anomalous rectification in
      response to large hyperpolarizations from rest. In voltage clamp, hyperpolarizing
      steps to command potentials more negative than -100 mV elicited IFast. Late
      firing neurons expressed little or no ISlow. 7. The properties of IFast were
      identical in both pyramidal and late-firing neurons. This current reversed at a
      potential negative to -70 mV. Its rate of current activation increased with the
      magnitude of the hyperpolarizing voltage step. This rate was approximately
      sevenfold faster than ISlow activation recorded at the same membrane potential.
      IFast was blocked by 2 mM extracellular Cs+ and reduced by 100 microM
      extracellular Ba2+. The threshold for activation of the underlying conductance
      was approximately -85 mV, with half-activation occurring at -112 mV. The
      properties of IFast were similar to those of the inward rectifier current
      previously identified in other central neurons. 8. Carbachol (40 microM) largely
      blocked IFast without affecting its rate of activation.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7507524
TI  - Imaging vascular endothelial activation: an approach using radiolabeled
      monoclonal antibodies against the endothelial cell adhesion molecule E-selectin.
AB  - E-selectin is an endothelial cell-specific adhesion molecule for leukocytes
      expressed on the luminal surface of vascular endothelium during inflammatory
      responses. Because E-selectin expression is dependent upon ongoing stimulation by
      cytokines, this molecule offers a potentially useful target for imaging tissues
      in disease states involving cytokine-mediated endothelial cell activation.
      METHOD: To assess the imaging potential of an anti-E-selectin monoclonal antibody
      (Mab) 1.2B6, the accumulation of intravenously injected 111In-labeled Mab 1.2B6
      was compared to that of 111In-control antibody in a model of arthritis in the
      pig. Injection of phytohaemagglutinin (PHA) into a knee led to E-selectin
      expression on vessels in the synovium and draining deep inguinal lymph nodes, as
      demonstrated by immunohistology. No E-selectin expression was seen in the control
      knee injected with buffer alone. Animals were given 111In-Mab 1.2B6 or 111In
      control antibody intravenously 3 hr after the intra-articular injection of PHA.
      Radiolabeled antibody uptake was measured by direct counting of tissues 25 hr
      postmortem. RESULTS: The accumulation of radiolabeled control IgG in synovium and
      draining deep inguinal lymph nodes of PHA-injected knees was significantly higher
      than accumulation in tissues injected with buffer alone; however, the comparable
      ratios in animals receiving radiolabeled Mab 1.2B6 were significantly greater.
      Scintigraphy performed 24 hr after 111In-Mab 1.2B6 injection showed obvious
      localization of activity in the inflamed knee in each of three animals.
      CONCLUSION: Radiolabeled anti-E-selectin Mab can be used to image localized
      inflammatory tissues. This approach may be useful for investigating activated
      endothelium in human disease.

PMID- 7507526
TI  - Blalock Taussig type shunt palliation for cyanotic infants and children.
AB  - In a period of ten years from January 1, 1979 to December 31, 1988, 54 cyanotic
      patients weighing less than 10 kg underwent shunt operations of Blalock Taussig
      type. The indications were hypercyanotic spells, failure to thrive and pulmonary
      arteries being too small for safe total collection. The commonest diagnosis was
      tetralogy of Fallot (63%). Thirty-three (64%) patients were older than 1 year but
      still weighed less than ten kg. Mortality was 16.67% (70% C.L. 8.94-26.60).
      During follow-up, there were 4(7%) late deaths. During the same period, 134
      patients less than 5 years age came to autopsy without having any cardiological
      or surgical intervention. Ninety-seven (72.4%) of these deaths were due to
      cardiac causes. In order to save their lives, early identification is necessary
      which highlights the importance of parent and primary physician education.

PMID- 7507525
TI  - Prenatal drug exposure: neurodevelopmental outcome and parenting environment.
AB  - Examined neurodevelopmental patterns and caregiving environment among 20 infants
      prenatally exposed to cocaine and 20 drug-free infants. The Brazelton Scale was
      administered 4 times. Drug-exposed infants had less optimal neurodevelopment than
      comparison infants at birth, but by 6 weeks only differences in autonomic
      stability were apparent. Neurodevelopmental performance was related positively to
      the child-centered quality of the environment. Though support buffered stress in
      both groups, the effect was more robust among drug-free mothers. Findings support
      the need to consider neurodevelopmental recovery and the caregiving environment
      in evaluations of developmental outcome among drug-exposed infants.

PMID- 7507527
TI  - Mapping of epitopes on the SmD molecule: the use of multiple antigen peptides to
      measure autoantibodies in systemic lupus erythematosus.
AB  - Autoantibodies against the ribonucleoproteins B, B' and D are a serological
      marker of systemic lupus erythematosus (SLE). We mapped the epitopes recognized
      by autoantibodies on the SmD molecule by means of 7 synthetic peptides
      corresponding to the entire length of the protein. By ELISA assay, 25% of the
      lupus sera contained IgG antibodies specific for the C-terminal SmD sequence 95
      119. This reactivity was confirmed by synthesizing the sequence as a multiple
      antigen peptide (MAP): antibodies reactive with the MAP 95-119 were present only
      in SLE and not in other connective tissue disorders. Sera containing high titers
      of anti-MAP 95-119 antibodies reacted in immunoblot with the SmD protein. These
      results indicate the presence of a dominant epitope in the C-terminal region of
      SmD, which is highly homologous to the Epstein-Barr virus induced nuclear protein
      EBNA I.

PMID- 7507528
TI  - Enhanced selectivity of oxytocin antagonists containing sarcosine in position 7.
AB  - Neurohypophyseal hormone analogues containing sarcosine (Sar) in position 7 were
      prepared to design more potent and selective oxytocin antagonists. The three
      analogues (1-3) of [Sar7]arginine-vasopressin ([Sar7]AVP) and six analogues (4-9)
      of [Sar7]arginine-vasotocin ([Sar7]AVT) had a reduced affinity for antidiuretic
      V2 receptors. The [Sar7]AVP derivatives (1-3) were potent antiuterotonic (in
      vitro pA2 = 7.5-8.4, in vivo 6.6-7.1) and antipressor (pA2 = 7.2-8.0) agents. The
      [Sar7]AVT analogues (4-9) were more potent and selective uterotonic antagonists
      (in vitro pA2 = 7.9-8.6, in vivo 7.1-7.5); their antipressor potencies were
      reduced (pA2 = 6.4-7.7). The change of the antagonistic potencies was paralleled
      by a change in the receptor affinities. Among other antiuterotonic analogues,
      [Mca1, D-Phe2, Sar7]AVT (4, Mca = beta-mercapto- beta,beta-cyclopentamethyl
      enepropionic acid) and [Mca1, D-Tyr(OEt)2,Sar7]AVT (6) were synthesized, two
      highly potent antiuterotonic compounds (in vitro pA2 = 8.3, in vivo 7.4 and 7.5,
      respectively) with reduced antipressor activity (pA2 = 6.4) and reduced binding
      affinity to V2 receptors (Kd = 421 and 35 nM, respectively) and no anti
      antidiuretic effect. Another potent antiuterotonic analogue, [Mca1,D-Trp2,
      Sar7]AVT (9, in vitro pA2 = 7.9, in vivo 7.5) has virtually no binding capability
      to V2 receptors (Kd approximately 0.3 mM). These analogues should lead to the
      design of even more potent and selective oxytocin antagonists.

PMID- 7507530
TI  - From the Centers for Disease Control and Prevention. Carbon monoxide levels
      during indoor sporting events--Cincinnati, 1992-1993.

PMID- 7507529
TI  - Resuscitation from hypovolemia in swine with intraosseous infusion of a saturated
      salt-dextran solution.
AB  - Prehospital fluid resuscitation of traumatic injury is limited by difficulty in
      delivering large volumes of fluid in the field and time delays associated with
      gaining vascular access. We addressed these limitations in 14 anesthetized swine
      by evaluating a highly efficient volume expander, a near-saturated salt-dextran
      solution (SSD) administered through a new device, which gains vascular access via
      intraosseous (IO) infusion into the sternal bone marrow. After a steady-state
      baseline was achieved, all animals were hemorrhaged to 45 mm Hg for one hour.
      Half of the hemorrhaged animals were infused intraosseously with either normal
      saline (NS) or SSD until cardiac output was restored to the baseline value. No
      further infusion was given and animals were monitored for 2 hours. Both regimens
      were able to restore cardiac output to the baseline value, but only 1.3 +/- 0.1
      mL/kg of SSD was required vs. 31.6 +/- 6.3 mL/kg for NS. In addition, cardiac
      output was better sustained after 2 hours with SSD than with NS. No deleterious
      effects of IO infusion of SSD were observed. From the improvement in
      cardiovascular variables and the lack of significant sternal or pulmonary
      pathologic perturbations, these data suggest that IO infusion of SSD can
      effectively treat hypovolemia and may allow field treatment when logistic
      considerations make conventional resuscitation impractical.

PMID- 7507531
TI  - [Successful collection of peripheral blood stem cells mobilized by a combination
      of G-CSF with high-dose Ara-C or high-dose etoposide].
AB  - The author evaluated the effectiveness of a combination of G-CSF with high-dose
      Ara-C (HD Ara-C) or high-dose etoposide based on the collection of peripheral
      blood stem cells (PBSC) during the recovery phase from myelosuppression in 17
      patients with various types of hematopoietic malignancies. Following therapy with
      HD Ara-C or HD etoposide, G-CSF (250 micrograms/body) was administered from the
      nadir state and blood mononuclear cells were collected using a CS-3000 by
      processing 15 litres of blood at each apheresis. Stem cell-enriched fractions
      obtained from discontinuous Percoll gradients were collected and stored in liquid
      nitrogen. The mean numbers of granulocyte-macrophage colony-forming units (CFU
      GM) obtained by the first apheresis were 10.9 x 10(5)/kg after chemotherapy with
      HD Ara-C and 13.4 x 10(5)/kg after HD etoposide therapy, respectively. In 14 out
      of the 17 first apheresis, more than 2 x 10(5) CFU-GM/kg were collected. Serial
      apheresis was performed in seven patients, at intervals ranging from 21-79 days,
      and the progenitor yield in the second apheresis decreased in five patients.
      These results suggest that the use of either HD Ara-C or HD etoposide induces an
      effective mobilization of PBSC and enables large scale collection of PBSC for
      autotransplantation.

PMID- 7507532
TI  - [The role of cytokines in the proliferation of leukemia cells in acute
      myelogenous leukemia].
AB  - Acute myelogenous leukemia is characterized by the infinite proliferation of
      malignant leukemia cells and by the impaired hematopoiesis. The proliferation of
      leukemia cells is supported by a small subpopulation, leukemic blast progenitors.
      Leukemic blast progenitors make leukemic blast colonies in methylcellulose
      culture. To determine the mechanism by which leukemia cells proliferate, we
      studied the role of several cytokines in the proliferation of leukemic blast
      progenitors in vitro. The findings indicated that there are at least three types
      in the regulation by cytokines of the leukemic cell growth. One is the
      stimulation of leukemic blast progenitors by colony-stimulating factors(CSFs) or
      interleukins(ILs) added in culture. These cytokines include granulocyte-CSF(G
      CSF), granulocyte-macrophage CSF (GM-CSF), IL-3 and IL-1. The second is the
      autocrine growth mechanism. Leukemia cells by themselves produce and secrete G
      CSF and GM-CSF, which stimulate the growth of leukemic blast progenitors. The
      third is a complex mechanism. IL-1, produced by leukemia cells or other cells,
      enhances the production of GM-CSF by leukemia cells, which stimulates the growth
      of leukemic blast progenitors. The precise mechanism by which each cytokine acts
      on leukemic blast progenitors should be determined to explore the mechanism of
      leukemia cell growth.

PMID- 7507533
TI  - [Neutrophil functions during treatment with granulocyte colony-stimulating factor
      (G-CSF) in the elderly with non-Hodgkin's lymphoma: including two patients
      accompanied with interstitial pneumonitis during the treatment with G-CSF].
AB  - We examined neutrophil functions in seven elderly patients with non-Hodgkin's
      lymphoma before and during treatment with granulocyte colony-stimulating factor
      (G-CSF) at the neutropenic stage after combination chemotherapy. Subcutaneous
      injection of 75 micrograms/d of G-CSF produced by E. coli was started when the
      neutrophil count decreased less than 1,500/microliter, and continued until the
      neutrophil count increased to about 10,000/microliter. The phagocytic activity of
      neutrophils from the elderly on day 3 of G-CSF treatment was markedly enhanced;
      1,129.9 +/- 403 ps/100 PMNs, which was 185.7 +/- 31.4% (p < 0.001) as compared
      with that before G-CSF treatment. The neutrophil alkaline phosphatase (NAP)
      activity was also enhanced on day 3; 398.3 +/- 48 score, which was 135.2 +/- 5.1%
      (p < 0.001) as compared with that before G-CSF treatment. Two patients developed
      interstitial pneumonitis during or shortly after the treatment with G-CSF.
      Interstitial pneumonitis suddenly developed when their neutrophil count was
      increased, and the phagocytic activity and NAP activity recovered. The phagocytic
      activity of neutrophils from them was enhanced to 1,090 +/- 26 ps/100 PMNs and
      772 ps/100 PMNs during the treatment with G-CSF, as compared with that before G
      CSF treatment of 644 +/- 29 ps/100 PMNs and 465 +/- 69 ps/100 PMNs, respectively.
      The NAP activity was also enhanced to 372 from 264. One patient suffered from
      transient pulmonary dysfunction during the treatment with G-CSF. His neutrophil
      count was more than 13,000/microliter, and the phagocytic activity enhanced to
      949 +/- 105 ps/100 PMNs. Dyspnea with suppressed PaO2 recovered reversibly after
      cessation of G-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507534
TI  - Effect of ammonium chloride on homocitrulline and homoarginine synthesis from
      lysine.

PMID- 7507535
TI  - Early structural changes in hypertension: pathophysiology and clinical
      consequences.
AB  - The structural upward resetting of heart, vessels, and barostat functions
      represents what may be the most important long-term cardiovascular alteration in
      hypertension; the altered geometric design of the systemic precapillary
      resistance vessels is of profound hemodynamic relevance. This is especially true
      in primary (essential) hypertension, for which three major etiological elements
      can be distinguished: polygenetic predisposition, environmental factors, and the
      structural factor. The physical and biological principles behind the early
      "structural upward resetting" of heart and vessels in hypertension are outlined
      and experimentally illustrated. Further, the long-term hemodynamic effects of
      this per se "normal" structural adaptation are discussed, particularly concerning
      systemic precapillary resistance, but also concerning the heart, barostat
      mechanisms of reflex and renal nature, and the venous capacitance vessels. With
      this background in mind, the primary long-term goal of therapy must be to reverse
      these structural changes toward normal cardiovascular design and dimensions,
      whereas in the future preventive measures may be actualized. Thus, treatment
      should serve not only to reduce the increased load on heart and vessels but also,
      wherever possible, to reduce the influence of trophic, growth-promoting factors
      of local and remote nature, as exemplified by model studies in rats.

PMID- 7507536
TI  - The transition from experimental to clinical pharmacology: the renin-angiotensin
      paradigm.
AB  - Modern molecular medicine is increasingly bridging the gap between basic research
      and experimental pharmacology and clinical therapeutics and practical medicine.
      The challenge in hypertension research is to elucidate the primary, genetic
      causes of elevated blood pressure. The problems with understanding primary
      (genetic) hypertension in humans are that (a) several genes are involved in the
      cardiovascular control mechanisms, (b) the genetics are complex, and (c)
      environmental factors that act over long spans of time confound the
      genotype/phenotype relationship individually, within a family, and regionally.
      Polygenetic diseases such as primary hypertension remain puzzles, which
      necessitates well-defined experimental models and new strategies in the genetics
      of human primary hypertension. This article will focus on the advances in
      molecular genetics of hypertension. Using gene technology it is possible to
      introduce new, additional genes in normotensive and hypertensive animals. In the
      mouse, it is possible to delete or mutate specific genes; similar technology is
      being developed for use in the rat.

PMID- 7507537
TI  - Protective effect of cilazapril on the cerebral circulation.
AB  - The goal of an antihypertensive treatment is to prevent "end-organ" damage.
      Cerebral vascular complications are among the most important because they are
      life threatening and can occur even at an early stage of the disease. Recently,
      it has been shown that cilazapril can decrease the mortality of stroke-prone
      rats, suggesting a decrease in the incidence of strokes, which occur
      spontaneously in these animals. The present article reviews the different
      functional and morphological changes that may explain the cerebral protective
      effects of cilazapril, such as the normalization of cerebral vascular reserve,
      decrease in the media, increase in the external diameter, and normalization of
      the mechanics and endothelial function of cerebral arterioles. In addition, the
      inhibition by cilazapril of injury-induced proliferation of smooth muscle cells
      and the infiltration of the endothelium by macrophages could prevent the
      development of atherosclerosis.

PMID- 7507538
TI  - Cardiac effects of ACE inhibition.
AB  - Hypertension frequently is associated with a number of changes in heart structure
      and function, such as left ventricular hypertrophy, disturbed diastolic function,
      and subnormal stroke volume during exercise. Most of these changes probably are
      related to myocardial fibrosis. Antihypertensive agents reverse the structural
      and functional changes to different degrees. The hemodynamic changes in central
      hemodynamics at rest and during exercise were studied before and after
      angiotensin-converting enzyme (ACE) inhibition in 68 patients with essential
      hypertension (ranging from severe to moderately severe). In patients with
      moderately severe hypertension who were administered perindoprilat intravenously,
      mean arterial pressure was reduced by approximately 17% due to reduction in total
      peripheral resistance and no changes in heart pump function. Chronic treatment
      with captopril, enalapril, or lisinopril for 6-12 months induced reduction in
      blood pressure associated with decreased peripheral resistance. In general, there
      were only minor changes in cardiac output, stroke volume, and heart rate. Studies
      from other laboratories have shown that ACE inhibitors reverse left ventricular
      hypertrophy and improve left ventricular diastolic function. Captopril also
      appears to improve coronary circulation. The effect of ACE inhibitors on heart
      structure and function appears promising with regard to cardioprotection during
      chronic use, but long-term studies are needed to prove that this will occur in
      clinical practice.

PMID- 7507539
TI  - ACE inhibitors: future perspectives.
AB  - There are chemical differences among angiotensin-converting enzyme (ACE)
      inhibitors that profoundly influence the pharmacokinetics and dynamics of
      different drugs. Differences in potency, affinity, and duration of action can be
      readily identified. These factors, together with individual binding
      characteristics of drug (or metabolite) to ACE, may influence the profile of
      hemodynamics and adverse effects, including first-dose hypotension and renal
      impairment. Differential inhibition of ACE in tissues (e.g., heart, brain,
      adrenal, kidney, blood vessel) could be important in identifying a particular ACE
      inhibitor for a specific clinical indication.

PMID- 7507540
TI  - Left ventricular hypertrophy: a pressure-independent cardiovascular risk factor.
AB  - Left ventricular hypertrophy (LVH), an increase in the muscle mass of the left
      ventricle, has been identified as a powerful risk factor for future
      cardiovascular morbidity and mortality. The risk of acute myocardial infarction,
      congestive heart failure, sudden death, and other cardiovascular events increases
      sixfold to eightfold with the occurrence of LVH. The increase in myocardial mass
      lowers coronary reserve and enhances cardiac oxygen requirements, gives rise to
      ventricular ectopy, and impairs left ventricular filling and contractility.
      Hypertension, obesity, advanced age, valvular heart disease, and other pathologic
      disorders that cause an increase in the hemodynamic burden can lead to LVH. LVH
      and its sequelae can be reduced by specific antihypertensive therapy, but despite
      these promising findings, future epidemiologic studies are necessary to document
      the clinical benefits of a reduction in LVH.

PMID- 7507541
TI  - Substance P antagonist does not block the stimulation of rapidly adapting
      pulmonary stretch receptors by ammonia.
AB  - We investigated the effects of the substance P (SP) blocker [D-Pro2,D-Trp7,9]-SP
      on the response of rapidly adapting pulmonary stretch receptors (RARs) to SP
      administered into the right atrium, or ammonia vapor inhaled into the lungs in
      anesthetized, spontaneously breathing rabbits. Right atrial administration of SP
      (0.3, 1.0, and 3.0 micrograms/kg) caused an increase in the RAR activity, and
      this increase became more prominent as the dose of SP was increased. The RARs
      increased their activity following inhalation of vapor from 5 and 10% ammonia
      solutions, and the increase was concentration dependent. The excitatory responses
      of RAR activity to SP at different doses were greatly diminished or completely
      blocked by administration of the selective SP antagonist (300 and 500
      micrograms/kg). However, the ammonia-induced RAR stimulation was not
      significantly altered by prior treatment with the SP blocker (300 and 500
      micrograms/kg). These results suggest that the stimulation of RARs by ammonia
      does not occur as a result of the release of SP from sensory nerves in the
      airways and lungs.

PMID- 7507543
TI  - Interferon for hepatitis A.

PMID- 7507544
TI  - Prostate specific antigen estimation with optical biosensor.

PMID- 7507542
TI  - Development of a rapidly computable descriptor of prostate tissue temperature
      during transurethral conductive heat therapy for benign prostate hyperplasia.
AB  - Benign prostate hyperplasia (BPH) is a condition in older men in which the mass
      of tissue in the prostate gland gradually increases over the course of many
      years, ultimately leading to urinary outflow obstruction. Current treatment of
      this condition is to surgically remove the obstructing tissue. One novel
      alternative therapy being studied is transurethral thermocoagulation of excessive
      prostatic mass. In this approach, a heat-emitting catheter is placed in the
      prostatic urethra, and the intraprostatic segment of the catheter is heated to
      temperatures above 60 degrees C for one hour. Two-dimensional cylindrical-co
      ordinate computer simulations of this treatment modality were run to model
      resultant temperature distributions within the prostate gland and surrounding
      tissues. The simulations revealed that resultant tissue temperature changes were
      related directly to the power delivered to the catheter and inversely to the rate
      of blood perfusion. Further analysis of the temperature profiles produced a
      rapidly computable predictor of tissue temperature in the radial dimension. Using
      the predictor, a 'kill radius' around the prostatic urethra can be easily
      computed on-line, during treatment, from clinically available data, catheter
      power and catheter temperature. The computed kill radius may serve as a useful
      predictor of the extent of thermal devitalization of unwanted obstructing tissue
      and the long-term success of the treatment in relieving urinary outflow
      obstruction without surgery.

PMID- 7507545
TI  - The intramuscular innervation of the human interarytenoid muscle.
AB  - The nerve supply of the human interarytenoid (IA) muscle has been controversial
      for more than a century. In this study the contribution of the recurrent and
      superior laryngeal nerves to the IA was investigated in 10 adult human larynges.
      The larynges were obtained from autopsies and processed with the modified
      Sihler's technique which clears soft tissue while staining nerve. The IA muscles
      were dissected off the specimens and transilluminated to demonstrate their nerve
      supply. The results demonstrated that all 10 IA muscles were bilaterally
      innervated by both recurrent laryngeal nerves (RLNs) as well as branches of both
      superior laryngeal nerves (SLNs). These nerves combined within the IA muscles to
      form a dense anastomotic plexus which was highly variable between specimens. The
      exact nature of the internal SLN neurons, whether motor or sensory, their
      innervation targets, or their function, were not discernible. Additional anatomic
      findings were the presence of large neural communications directly between the
      SLN and RLN, and smaller neural connections from side to side. All of these
      results disagree with currently accepted descriptions of laryngeal neuroanatomy.

PMID- 7507546
TI  - Deposition of C3, the terminal complement complex and vitronectin in primary
      biliary cirrhosis and primary sclerosing cholangitis.
AB  - Characteristics of primary biliary cirrhosis (PBC) and primary sclerosing
      cholangitis (PSC) are bile duct destruction and portal inflammation. Increased
      levels of circulating complement activation products are also present. This
      raises the possibility of involvement of complement-dependent cytotoxic
      mechanisms in the pathogenesis. Therefore, we investigated liver biopsy specimens
      from 21 patients with PBC, six patients with PSC and six controls for complement
      deposits by immunohistochemistry using polyclonal and monoclonal antibodies
      against C3d, the terminal complement complex (TCC) and vitronectin (S-protein).
      We found C3d, TCC and vitronectin deposits only in the portal tracts. C3d and TCC
      were present in the walls of the hepatic arteries and in the connective tissue
      stroma but never around the bile ducts. We found vitronectin deposits throughout
      the connective tissue, often independent of the TCC deposits. When vitronectin
      and TCC were co-localized, the staining patterns were inverse; that is, intense
      staining for TCC accompanied weak staining for vitronectin and vice versa.
      Occasionally complete dissociation between TCC and vitronectin staining was
      observed. Deposits of TCC and vitronectin showed a focal distribution leaving
      many portal tracts free of TCC. Our results question whether complement-dependent
      cytotoxic mechanisms take part in the bile duct destruction in PBC and PSC.

PMID- 7507548
TI  - Prenatal vitamins. A rite of passage?

PMID- 7507549
TI  - [The discovery of America and medicine].

PMID- 7507547
TI  - Hepatitis C virus infection in anti-HIV positive and negative French homosexual
      men with chronic hepatitis: comparison of second- and third-generation anti-HCV
      testing.
AB  - To determine the prevalence of hepatitis C virus (HCV) infection in homosexuals
      with chronic hepatitis, we tested for anti-HCV antibodies 113 (47 anti-HIV
      positive) French non-drug-addicted homosexual men admitted for chronic viral
      hepatitis. Anti-HCV were detected with second- and third-generation ELISAs
      (ELISA2 and ELISA3) and RIBAs (RIBA2 and RIBA3). Chronic hepatitis was related to
      non-A, non-B infection in four, to hepatitis D virus (HDV) infection in five and
      to hepatitis B virus (HBV) infection in 104 patients. Anti-HCV positivity was
      found in 50.4% and 12.4% of the 113 patients, with ELISA2 and ELISA3,
      respectively. Positivity with RIBA2 and RIBA3 was found in only six of the 57
      ELISA2 positive patients (all six were ELISA3 positive). The high prevalence of
      positivity with ELISA2 not confirmed by RIBA2 or RIBA3 suggests false-positive
      results. ELISA2 positive results were more frequent with frozen serum samples
      than with fresh serum samples (62% vs 23.5%, p = 0.0003). However, even with
      fresh serum, ELISA2-positive RIBA-negative results remained frequent in anti-HIV
      positive patients. ELISA3 seems to give more specific results. We conclude that
      the prevalence of HCV infection, as assessed with RIBA, was 5.3% among French
      homosexual men with chronic hepatitis (3.8% after exclusion of transfused
      patients). This low prevalence suggests that homosexual transmission of HCV is
      relatively uncommon.

PMID- 7507550
TI  - Burkholderia pseudomallei and melioidosis: be aware in temperate area.

PMID- 7507551
TI  - Organization of ribosomal RNA genes in Borrelia burgdorferi sensu lato isolated
      from Ixodes ovatus in Japan.
AB  - Borrelia burgdorferi sensu lato was obtained from adult ixodid ticks, Ixodes
      ovatus, collected in Nagano, Japan, and was named NT112. The genomic DNA was
      digested with enzymes, electrophoresed, blotted and hybridized with rRNA gene
      probes obtained from B. burgdorferi sensu stricto B31. The results showed that
      the borrelial chromosome contains a single rrs (16S rRNA gene) sequence and two
      copies of rrl/rrf (23S/5S rRNA genes) sequences. The rrl/rrf genes were tandemly
      repeated at intervals of 3.2 kb and were located separately from the rrs gene on
      the genome. Our findings indicate that the organization of rRNA genes in Borrelia
      from I. ovatus ticks is identical to that of B. burgdorferi sensu stricto.

PMID- 7507552
TI  - [Sensory neuropeptides: pro-inflammatory or protective effect in the intestine?].

PMID- 7507553
TI  - [The temporomandibular joint (TMJ) and osteogenesis imperfecta. A study of its
      embryologic development].
AB  - Although the most common oral manifestation of osteogenesis imperfecta is
      dentinogenesis imperfecta, several authors have described jaw fractures and
      radiolucent bone lesions associated with this disease. The authors, after
      reporting the main features of this disease, compare the cranial embryologic
      growth in twice fetuses of a 15 weeks old: one of these with osteogenesis
      imperfecta.

PMID- 7507554
TI  - Modulation of toxicity by diet and dietary macronutrient restriction.
AB  - Restriction of diet and macronutrients has been reported to modulate the toxicity
      of numerous chemical agents. Of the various forms of restriction studied, using
      nutritionally adequate diets, food restriction (FR) appears to be most effective,
      but protein restriction (PR), fat restriction (FtR), carbohydrate restriction
      (CbR), and excess of dietary fiber (FE) also affect toxicity and the spontaneous
      diseases that define the background incidence in toxicity tests. The
      heterogeneity of the dietary macronutrients complicates simple analysis of their
      effects. Additionally, the interrelationships between these various components in
      the complex dietary mixture often make experiments difficult to interpret.
      Despite these complexities, a simple model is presented, which considers the
      effects of dietary manipulations on the individual steps in the interaction of
      organism and agent, and puts the varied effects that can occur within an organism
      into context. Ultimately, many of the effects of dietary modulation on these
      steps in toxicogenesis can be considered as changing agent exposure and the
      biologically available dose. The effects of macronutrient restriction are
      discussed in terms of effects on agent at the interface of organism and toxicant,
      agent disposition, agent metabolism, and repair of toxicant-induced damage at the
      level of the genome. After illustrating the influence of these nutritional
      effects on the chronic bioassay, using mouse liver tumors as an example, the
      significance of these effects for chronic and short-term testing is discussed.
      Additionally, methods to address the impact of nutritional factors on toxicity
      testing are suggested.

PMID- 7507555
TI  - Protein restriction (PR) and caloric restriction (CR) compared: effects on DNA
      damage, carcinogenesis, and oxidative damage.
AB  - Protein restriction (PR) and caloric restriction (CR) similarly impinge upon
      various physiological factors that can significantly inhibit the growth of DNA
      damaged tissue and, therefore, carcinogenesis. Whether this effect is largely, or
      only in part, due to simple inhibition of body weight gain is examined. Among
      their many other health-improving effects, PR and CR delay the onset of puberty.
      It has been suggested that animals have developed mechanisms to cope with lean
      periods and that, when food is limited, resources are diverted from those
      physiological functions that offer no benefit for immediate survival (e.g.,
      reproductive capacity) to thereby support an increase in the maintenance
      functions that prolong life. PR has also been shown to affect numerous other
      varied mechanisms that can affect carcinogenesis, including gene expression and
      metabolism of xenobiotics. The effects of PR on initiational and promotional
      growth of DNA-damaged tissue is also discussed. PR also seems to boost
      antioxidant defenses and inhibit the accumulation of oxidative damage (as does
      CR). Protein restricted animals have been shown to accumulate more calories, but
      develop fewer preneoplastic lesions and tumors than their high-protein
      counterparts. This observation seems quite counter to most ideas about dietary
      restrictions and CR. Despite the fact that both PR and CR induce many beneficial
      physiological effects in common, it is possible that PR is the more feasible
      option for human consideration. The levels of PR likely to improve health without
      negative side effects are discussed.

PMID- 7507556
TI  - Modulation of oxidative DNA damage levels by dietary fat and calories.
AB  - Decreased dietary intake of fat and/or calories generally results in a lower
      incidence of mammary gland tumors in rodents. Feeding of either low-fat or
      calorie-restricted diets to rats also has been shown to result in decreased
      levels of oxidative DNA damage. Since oxidative DNA damage is suggested to have a
      role in carcinogenesis, this may be one mechanism by which dietary change can
      reduce cancer risk. The effects of calorie-restricted diets on both oxidative DNA
      damage levels and mammary gland tumor incidence are generally more pronounced
      than that of low-fat diets. There is, however, some difficulty in defining what
      amount of fat should be used to prepare 'low-fat' and 'high-fat' rodent diets as
      well as what a suitable fat intake for control diets should be in studies that
      examine the effects of dietary fat and/or calories on tumorigenesis. In
      particular, the promoting effects of dietary fat may be exerted only up to a
      certain level of fat, above which no further effect is observed. Another
      difficulty in the interpretation of the results is that there may be a time
      dependent effect of high fat diets on oxidative damage, with increased damage
      resulting only when the diets are fed for longer periods of time. The appropriate
      experimental approach to model human dietary exposures therefore remains to be
      determined. Although the effects of caloric intake on mammary gland tumorigenesis
      appear to be more pronounced than that of fat intake, low-fat diets still may be
      useful as a preventive measure in human populations to reduce breast cancer risk
      for individuals who cannot safely reduce their caloric intake.

PMID- 7507557
TI  - Caloric restriction, aging, and antioxidant enzymes.
AB  - The basic mechanisms of aging and its retardation by caloric restriction (CR)
      remain unclear. One suggested means by which CR could retard aging is based on
      production of mitochondrial free radicals, and efficiency of their subsequent
      metabolism. Currently, there is little information concerning the influences of
      age and CR on the rates of in vivo mitochondrial free radical production.
      However, evidence for CR-induced modulation of free radical detoxification
      capacities is mounting. The direction of the influence of CR on free radical
      detoxification is tissue-specific. These effects are broad and appear to provide
      positive advantage.

PMID- 7507558
TI  - Effects of caloric restriction on rodent drug and carcinogen metabolizing
      enzymes: implications for mutagenesis and cancer.
AB  - Caloric restriction in rodents results in increased longevity and a decreased
      rate of spontaneous and chemically induced neoplasia. The low rates of
      spontaneous neoplasia and other pathologies have made calorically restricted
      rodents attractive for use in chronic bioassays. However, caloric restriction
      also alters hepatic drug metabolizing enzyme (DME) expression and so may also
      alter the biotransformation rates of test chemicals. These alterations in DME
      expression may be divided into two types: (1) those that are the direct result of
      caloric restriction itself and are detectable from shortly after the restriction
      is initiated; (2) those which are the result of pathological conditions that are
      delayed by caloric restriction. These latter alterations do not usually become
      apparent until late in the life of the organism. In rats, the largest direct
      effect of caloric restriction on liver DMEs is an apparent de-differentiation of
      sex-specific enzyme expression. This includes a 40-70% decrease in cytochrome
      P450 2C11 (CYP2C11) expression in males and a 20-30% reduction of corticosterone
      sulfotransferase activity in females. Changes in DME activities that occur late
      in life in calorically restricted rats include a stimulation of CYP2E1-dependent
      4-nitrophenol hydroxylase activity and a delay in the disappearance of male
      specific enzyme activities in senescent males. It is probable that altered DME
      expression is associated with altered metabolic activation of chemical
      carcinogens. For example the relative expression of hepatic CYP2C11 in ad libitum
      fed or calorically restricted rats of different ages is closely correlated with
      the amount of genetic damage in 2-acetylaminofluorene- or aflatoxin B1-pretreated
      hepatocytes isolated from rats of the same age and caloric intake. This suggests
      that altered hepatic drug and carcinogen metabolism in calorically restricted
      rats can influence the carcinogenicity of test chemicals.

PMID- 7507559
TI  - Effect of caloric restriction on the metabolic activation of xenobiotics.
AB  - The effect of caloric restriction (CR) on xenobiotic metabolizing enzyme
      activities results in alterations in the metabolic activation of chemical
      carcinogens, with a resultant impact on DNA-carcinogen adduct formation and DNA
      repair. Using aflatoxin B1 (AFB1) and benzo[a]pyrene (BP) as model carcinogens,
      we studied the effect of CR on the metabolic activation of these carcinogens and
      carcinogen-induced DNA damage and repair in terms of AFB1-DNA and BP-DNA adduct
      formation and removal. Male Fischer 344 rats fed calorie restricted diets (60% of
      the food consumption for ad libitum-fed rats) showed a reduction in the metabolic
      activation of AFB1 and decrease in both the in vitro and in vivo AFB1-DNA adduct
      formation. However, CR increased the activity of BP metabolizing enzymes
      resulting in an enhancement of BP-DNA adduct formation. Our results indicate that
      the effect of CR on metabolic activation of xenobiotics is dependent upon the
      selected xenobiotic metabolizing enzymes whose activities may be significantly
      altered by CR, and upon the nature of the chemical carcinogens which exert
      different structure-activity relationships during the process of chemically
      induced carcinogenesis.

PMID- 7507560
TI  - Effect of dietary restriction on DNA repair and DNA damage.
AB  - Dietary restriction is the only experimental manipulation known to extend
      lifespan and retard aging in mammals. Therefore, it is a powerful tool for
      identifying cellular processes that are involved in aging and senescence.
      Recently, several laboratories have begun to examine the effects of dietary
      restriction on the integrity of the genome and the ability of cells to repair
      DNA. In most studies, it was found that the repair of DNA damage, as measured by
      unscheduled DNA synthesis, was significantly higher in cells isolated from
      rodents fed calorie-restricted diets compared to cells isolated from rodents fed
      ad libitum. Dietary restriction also was observed to be associated with a
      reduction of the levels of certain types of DNA damage; however, preliminary
      experiments suggest that the effect of dietary restriction on the age-related
      accumulation of DNA damage depends on the type of DNA damage studied.

PMID- 7507561
TI  - Biomarkers of aging: correlation of DNA I-compound levels with median lifespan of
      calorically restricted and ad libitum fed rats and mice.
AB  - I-compounds are species-, tissue-, genotype-, gender-, and diet-dependent bulky
      DNA modifications whose levels increase with animal age. While a few of these DNA
      modifications represent oxidation products, the majority of I-compounds appear to
      be derived from as yet unidentified endogenous DNA-reactive intermediates other
      than reactive oxygen species. Circadian rhythms of certain I-compounds in rodent
      liver imply that levels of these DNA modifications are precisely regulated.
      Caloric restriction (CR), the currently most effective method available to retard
      aging and carcinogenesis, has been previously shown to elicit significant
      elevations of I-compound levels in tissue DNA from Brown-Norway (BN) and F-344
      rats as compared to age-matched ad libitum fed (AL) animals. The present
      investigation has extended this work by examining liver and kidney DNA I-compound
      levels in three genotypes of rats (F-344, BN, and F-344 x BN) and two genotypes
      of mice (C57BL/6N and B6D2F1) under identical experimental conditions in order to
      determine whether correlations exist between I-compound levels, measured in
      middle-aged animals, and median lifespan. Levels of a number of liver and kidney
      I-compounds were found to display genotype- and diet-dependent, statistically
      significant positive linear correlations with median lifespan in both species. In
      particular, the longer-lived hybrid F-344 x BN rats and B6D2F1 mice tended to
      exhibit higher I-compound levels than the parent strains. CR enhanced I-compound
      levels substantially in both rats and mice. Thus, I-compounds, measured at middle
      age, reflected the functional capability ('health') of the organism at old age,
      suggesting their predictive value as biomarkers of aging. The positive linear
      correlations between levels of certain I-compounds (designated as type I) and
      lifespan suggest that these modifications may be functionally important and thus
      not represent endogenous DNA lesions (type II), whose levels would be expected to
      correlate inversely with lifespan.

PMID- 7507562
TI  - Age-related changes in expression and activity of DNA polymerase alpha: some
      effects of dietary restriction.
AB  - DNA polymerase alpha (pol alpha) purified from human diploid fibroblasts (HDF)
      and from livers of C57BL/6N mice showed age-related decreases in: (1) mRNA
      levels; (2) the amount of enzyme isolated per cell; and (3) enzyme activity
      (HDF); as well as: a) the amount of enzyme isolated; b) the specific activity;
      and c) the enzyme fidelity (liver). Hepatic pol alpha from dietary restricted
      (DR) mice exhibited less of a decline in specific activity and copied synthetic
      DNA templates with relatively higher fidelity than did enzymes from animals fed
      ad libitum (AL). Pol alpha from fetal-derived HDF exhibited increased expression
      compared with aged donor-derived HDF, with both fetal and old cell pol alpha in
      normal cells being expressed at lower levels than in their transformed cell
      corollaries. Treatment of human pol alpha from aged donor-derived HDF with a pol
      alpha accessory protein isolated from log phase murine cells resulted in
      increased pol alpha binding of DNA and increased pol alpha activity. However,
      highly active pol alpha isolated from fetal-derived or transformed HDF, or from
      transformed murine cells, showed little or no activity enhancement in the
      presence of accessory protein. These data indicate that, as a function of
      increased age, there is a decrease in pol alpha expression and specific activity
      in HDF, as well as decreases in specific activity and fidelity of pol alpha in
      essentially amitotic murine hepatic tissues. Dietary restriction impedes the age
      related declines in both activity and fidelity of hepatic pol alpha in mice. The
      data further indicate that transformation of slowly dividing HDF is associated
      with increased expression of pol alpha, but suggest that increased expression
      alone is not sufficient to explain the difference in polymerase activity levels
      between parental and transformed HDF. Lastly, the data suggest that interaction
      of pol alpha with an essential accessory protein may be altered as a function of
      age, an alteration that appears to be correlated with the decline in pol alpha
      DNA binding and specific activity.

PMID- 7507563
TI  - Effects of caloric restriction in animals on cellular function, oncogene
      expression, and DNA methylation in vitro.
AB  - While the life-extending and disease-modulating effects of caloric restriction
      (CR) are well documented in whole animal studies and in correlative experiments
      using cells taken from CR animals, very few studies have used cells in culture
      after their removal from the CR-fed animal. In using this in vivo-->in vitro
      approach we have attempted to examine the proposition that the effects of CR can
      be transferred to individual cells by analyzing the cellular functions of
      proliferation and transformation, the activation of oncogenes, and the
      methylation of DNA as a function only of diet. Pancreatic acinar cells excised
      from CR-fed Brown-Norway rats and placed in rich medium showed different
      responses compared to cells from ad libitum (AL)-fed controls. CR had the effect
      of slowing growth rate and protecting against spontaneous and N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG)-induced transformation over 14 passages of cells in
      culture. At the molecular level, cells from the CR animals showed reduced c-Ha
      ras oncogene expression and mutation as well as reduced mutation of the p53
      suppressor gene. CR also increased genomic methylation of ras DNA. We conclude
      that the effects of CR treatment of the animal are transferred to individual
      cells and note that these responses (decreased proliferation and transformation;
      depressed oncogene expression and mutation and decreased suppressor gene
      mutation; and increased oncogene methylation) are cellular and molecular analogs
      of in vivo weight loss, life extension, and carcinogenesis modulation, which are
      hallmarks of CR in the whole animal. The fact that these responses are seen
      generations after the cells are removed from the CR-treated animal indicates that
      CR causes a permanent predisposition of pancreatic acinar cells to these
      modulated responses and shows the value of the in vivo-->in vitro protocol in
      studies that relate diet to cellular and molecular function.

PMID- 7507564
TI  - The frequency of micronuclei with X chromosome increases with age in human
      females.
AB  - The rate of micronuclei counted on lymphocyte cultures from five healthy female
      donors, 27-80 years old, increased with age. Using pXBR1 probe, specific for the
      alphoid DNA of the X chromosome, the presence of this chromosome was investigated
      by FISH (fluorescence in situ hybridization) in both micronuclei and metaphases.
      Both X aneuploidy and frequency of X chromosome per micronuclei increased with
      age. However, this overinvolvement of X chromosome was not sufficient to explain
      the overall increase of micronuclei with age, suggesting that autosomes are also
      involved. Thus, the higher increase of X than autosome aneuploidy in lymphocytes
      may result from both an excess of X chromosome losses and a better survival of
      cells with a monosomy X.

PMID- 7507565
TI  - Age-dependent somatic excision of transposable element Tc1 in Caenorhabditis
      elegans.
AB  - The Tc1 element of the free-living nematode Caenorhabditis elegans is a well
      characterized transposon that is present in 30-500 copies per haploid genome,
      depending on the strain. Excision of Tc1 elements, which occurs readily in
      somatic tissues during larval development, has not previously been examined
      during aging of adult worms. We have identified a recently inserted Tc1 element
      in the KR1787 mutator strain of C. elegans and have found that Tc1 somatic
      excision at that site increases by more than 14-fold during the organism's
      lifespan.

PMID- 7507566
TI  - Cloning of cDNAs with possible association with senescence and immortalization of
      human cells.
AB  - Normal human diploid fibroblasts (HDF) have a finite life span in vitro and have
      been used as a model system for the study of in vivo aging. Little is known about
      how changes in gene expression may affect the immortalization of human
      fibroblasts. We looked for cDNA clones whose mRNAs were differentially expressed
      between mortal senescent SV40-transformed human fibroblasts (B-32) and the
      immortal counterparts (B-32F) derived from B-32 cells. We identified three cDNA
      isolates by subtractive differential hybridization with 32P-labeled cDNA probes
      from B-32 cells and B-32F cells. Nucleotide sequence analysis of these cDNA
      clones revealed that they were homologous to the human vimentin, a human
      mitochondrial gene and a human gene of unknown nature. Slot blot and Northern
      blot analyses demonstrated that the former two were preferentially expressed in
      senescent B-32 cells and the last one was less expressed in B-32F immortal cells.

PMID- 7507567
TI  - Correlation between senescence and DNA repair in cells from young and old
      individuals and in premature aging syndromes.
AB  - Cellular aging appears to be related to and perhaps caused by diminished DNA
      repair. To elucidate direct correlations between DNA repair capacity and
      senescence various parameters of cellular aging and DNA repair were studied
      simultaneously. Of special interest are features of DNA repair and senescence in
      cultured diploid fibroblasts derived either from healthy young or elderly
      probands as well as from patients suffering from premature senescence syndromes
      (Werner syndrome, Cockayne syndrome, ataxia telangiectasia and Down syndrome).
      Here we demonstrate the striking parallelism between reduced maximal lifespan,
      elevated levels of spontaneous chromosomal breaks, higher incidence of formation
      of micronuclei, a significant prolongation of cell cycle duration and a
      diminished reactivation of in vitro injured plasmid after transfection in cells
      from old individuals and from patients with premature senescence syndromes,
      suggesting a causal relationship between senescence and DNA damage.

PMID- 7507568
TI  - Aneuploidy in somatic cells of in utero exposed A-bomb survivors in Hiroshima.
AB  - Cytogenetic data on cultured lymphocytes of the in utero exposed A-bomb survivors
      in the RERF Adult Health Study cohort have been analyzed using the G-banding
      technique to determine the frequency of aneuploid cells. The data consist of
      blood samples collected between 1985 and 1987 from 264 Hiroshima individuals for
      whom DS86 maternal uterine dose estimates are available: 124 proximally exposed
      (74 males and 50 females) with an estimated dose of 0.005 Sv or more, and 140
      distally exposed (76 males and 64 females) with a dose estimate of 0 Sv, assuming
      the neutron relative biological effectiveness (RBE) of 10. A main feature of
      aneuploidy was that aneuploid frequency in autosomes depended generally on
      chromosome length; aneuploidies were significantly more frequent in shorter
      chromosomes than in longer chromosomes. The frequency of aneuploidies also
      depended on type, with chromosome loss approximately five times more frequent
      than chromosome gain. However, chromosome 21, as well as the sex chromosomes,
      were notable in that aneuploidy was much more frequent for these chromosomes than
      would be predicted from a simple relationship with length. X chromosome
      aneuploidies were significantly more frequent in females than in males. There was
      no dependence of aneuploid frequencies on dose when measured 40 years after the
      exposure.

PMID- 7507570
TI  - Ionizing radiation and genetic risks. V. Multifactorial diseases: a review of
      epidemiological and genetic aspects of congenital abnormalities in man and of
      models on maintenance of quantitative traits in populations.
AB  - This paper discusses (a) data on the epidemiological and etiological aspects of
      human congenital abnormalities, (b) the multifactorial threshold model and other
      models which have been proposed to explain their inheritance patterns and
      recurrence risks in families and (c) current concepts on mechanisms on the
      prevalence of heritable variation for quantitative traits in populations.
      Congenital abnormalities, which afflict an estimated 6% of all live births, are
      etiologically heterogeneous. The majority of these do not follow Mendelian
      transmission patterns, but do 'run' in families. The multifactorial threshold
      model is an extension of genetic principles developed for quantitative traits to
      all-or-none traits; in its simplest formulation, it assumes the existence in the
      population of an underlying normally distributed 'liability' (which is due to
      numerous genetic and environmental factors acting additively, each contributing a
      small amount of liability) and of a 'threshold' beyond which the individual is
      affected. For most congenital abnormalities, the nature of these factors remains
      unknown. Other models assume fewer causal factors although, again, these remain
      to be identified. The question of how considerable heritable variation for most
      quantitative/polygenic traits has come to exist is a long-standing one in
      evolutionary population genetics. Models postulating that its existence is
      consistent with a balance between recurrent mutation and stabilizing selection or
      suggesting the possible operation of other mechanisms have been published in the
      literature. In the absence of knowledge on mechanisms responsible for the stable
      prevalences of congenital abnormalities or other multifactorial conditions in the
      population (but which is required to predict the consequences of an increase in
      mutation rate on their prevalences) it is necessary (a) to adapt and use concepts
      derived from quantitative and evolutionary population genetics and (b) to examine
      how sensitive the predictions are to the assumptions used, and how consistent
      they are with biological realities.

PMID- 7507569
TI  - Protonation of the imidazole ring prevents the modulation by histidine of
      oxidative DNA degradation.
AB  - When supercoiled DNA is incubated with Fe(II) at pH 7 in the presence of hydrogen
      peroxide, the rate of nicking first increases with increasing H2O2 concentration
      to reach a maximum, then decreases and eventually increases again. When 0.1 mM
      histidine is added at neutral pH at low H2O2 concentration (< 3 mM), it hinders
      the nicking of DNA; when it is added at high H2O2 concentrations (> 10 mM), it
      enhances the rate of nicking. When similar experiments are performed at slightly
      acidic pH (4.5) the biphasic behavior is maintained, independent of the presence
      of histidine. One can conclude that the protonation of imidazole (pK = 5.9)
      abolishes the capability of histidine to modulate the oxidative degradation of
      DNA. Results of electron spin resonance experiments suggest that at low H2O2
      concentration, the protective effect of histidine could be the consequence of its
      capability to bind OH. radicals.

PMID- 7507571
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Oxidative DNA damage--the effects of certain genotoxic and
      operationally non-genotoxic carcinogens.
AB  - A wide variety of oxidative DNA lesions are commonly present in untreated human
      and animal DNA. One of these lesions, 8-hydroxydeoxyguanosine, has been shown to
      lead to base mispairing (mutation) on DNA replication. Other lesions remain to be
      investigated in this respect. Oxidative DNA lesions on cell replication may, in
      appropriate circumstances, lead to proto-oncogene activation. Oxidative DNA
      damage, on fixation, may also lead to cytotoxicity followed by regenerative
      proliferation. The probable or possible importance of oxidative DNA damage is
      reviewed for various classes of carcinogens and natural processes, including
      metal ions, high-energy radiation, miscellaneous chemicals, tumor-promoting
      agents, polyhydroxyphenols/quinones, lipid metabolism, peroxisome proliferators
      and thyroid function. It is concluded that although the evidence needs
      considerable strengthening in many of these examples, the available information
      indicates the potential importance of oxidative DNA damage in the induction of
      tumors by these agents. It is also possible that non-cancerous degenerative
      diseases associated with aging are the result of the accumulation of lesions
      resulting from unrepaired oxidative DNA damage.

PMID- 7507572
TI  - Review of the genotoxicity of nitrogen oxides.
AB  - Nitrogen oxides (NOx) are formed in combustion processes and are major pollutants
      in urban air. Relatively few studies on the genotoxicity of NO2 and NO have been
      performed. These studies indicate that NO2 is genotoxic in vitro, but the effect
      of NO seems to be very slight. One in vivo study showed chromosome aberrations
      and mutations in lung cells after inhalation of NO2 (and NO), but tests for
      chromosome aberrations in lymphocytes and spermatocytes or micronuclei in bone
      marrow were negative after inhalation of NO2. Based on present studies, there is
      no clear evidence of a carcinogenic potential of NO2, although lung adenomas were
      induced in the susceptible strain A/J mouse. The primary metabolites of NOx are
      nitrite and nitrate. Nitrate seems to be devoid of genotoxic properties, but
      nitrite is genotoxic in vitro, and there are also positive in vivo results.
      Cancer studies have been mainly negative. However, carcinogenic nitrosamines have
      been shown to be formed in vivo after inhalation of NO2. Nitrogen oxides are key
      components in atmospheric smog formation, which may lead to secondary effects.
      Strongly mutagenic nitro-PAH compounds are easily formed, and mutagenic reaction
      products may be formed photochemically from alkenes.

PMID- 7507573
TI  - Genotoxicity of mercury compounds. A review.
AB  - This article reviews literature data concerning the genotoxicity of 29 mercury
      containing agents, including laboratory compounds as well as ingredients of
      preparations used as fungicides, dyes, disinfectants and drugs. A variety of
      genetic end-points were investigated in bacteria, yeasts, moulds, plants,
      insects, cultured cells from fishes, rodents or humans, aquatic organisms,
      amphibians, mammalia and exposed humans. The overall evaluation is quite complex.
      Mercury compounds failed to induce point mutations in bacteria but often exerted
      clastogenic effects in eukaryotes, especially by binding SH groups and acting as
      spindle inhibitors, thereby causing c-mitosis and consequently aneuploidy and/or
      polyploidy. Inorganic mercury compounds were also found to induce the generation
      of reactive oxygen species and glutathione depletion in cultured mammalian cells.
      Although different mercury compounds tended to produce qualitatively comparable
      genetic effects, which suggests the involvement of a common toxic entity,
      methylmercury derivatives and other ionizable organomercury compounds were more
      active in short-term tests than either non-ionizable mercury compounds (e.g.,
      dimethylmercury) or inorganic mercury salts (e.g., mercuric chloride). The
      results of cytogenetic monitoring in peripheral blood lymphocytes of individuals
      exposed to elemental mercury or mercury compounds from accidental, occupational
      or alimentary sources were either negative or borderline or uncertain as to the
      actual role played by mercury in some positive findings. Both genotoxic and non
      genotoxic mechanisms may contribute to the renal carcinogenicity of mercury,
      which so far has been convincingly demonstrated only in male rodents treated with
      methylmercury chloride.

PMID- 7507574
TI  - Mutagenicity, carcinogenicity and teratogenicity of vanadium compounds.
AB  - The mutagenic, carcinogenic and teratogenic effects of vanadium and its compounds
      are reviewed. It is concluded that vanadium is not clastogenic and only weakly
      mutagenic; it has marked mitogenic activity affecting the distribution of
      chromosomes during mitosis and possibly causing aneuploidy. The few positive data
      on effects of vanadium during development leave it open whether direct effects on
      the embryo of fetus or physiological disturbances in the mother are responsible.
      No data exist indicating that vanadium is carcinogenic in animals or man, but
      since it interferes with mitosis and chromosome distribution, the possibility
      that vanadium might be carcinogenic under certain conditions cannot be dismissed
      offhand.

PMID- 7507575
TI  - Dendritic regression dissociated from neuronal death but associated with partial
      deafferentation in aging rat supraoptic nucleus.
AB  - As neurons are lost in normal aging, the dendrites of surviving neighbor neurons
      may proliferate, regress, or remain unchanged. In the case of age-related
      dendritic regression, it has been difficult to distinguish whether the regression
      precedes neuronal death or whether it is a consequence of loss of afferent
      supply. The rat supraoptic nucleus (SON) represents a model system in which there
      is no age-related loss of neurons, but in which there is an age-related loss of
      afferents. The magnocellular neurosecretory neurons of the SON, that produce
      vasopressin and oxytocin for release in the posterior pituitary, were studied in
      male Fischer 344 rats at 3, 12, 20, 27, 30, and 32 months of age. Counts in Nissl
      stained sections showed no neuronal loss with age, and confirmed similar findings
      in other strains of rat and in mouse and human. Nucleolar size increased between
      3 and 12 months of age, due, in part, to nucleolar fusion, and was unchanged
      between 12 and 32 months of age, indicating maintenance of general cellular
      function in old age. Dendritic extent quantified in Golgi-stained tissue
      increased between 3 and 12 months of age, was stable between 12 and 20 months,
      and decreased between 20 and 27 months. We interpret the increase between 3 and
      12 months as a late maturational change. Dendritic regression between 20 and 27
      months was probably the result of deafferentation due to the preceding age
      related loss of the noradrenergic input to the SON from the ventral medulla.

PMID- 7507576
TI  - Polyamine modulation of excitatory amino acid responses in the rat cortical
      wedge.
AB  - Rat neocortex slices in Mg2+ free buffer show spontaneous discharges which have a
      constant frequency and are dependent on N-methyl-D-aspartate (NMDA) receptor
      activation. Spermine increased the frequency of discharges at concentrations
      below 1 mM, had biphasic effects at 1 mM, and only decreased the frequency of
      discharges at 3 mM. In contrast, the amplitude of these discharges was only
      reduced by spermine in a concentration dependent manner (300 microM to 3 mM).
      Spermidine produced similar effects, but was a less potent inhibitor of discharge
      frequency and amplitude than spermine. Diethylenetriamine (DET) 300 microM did
      not significantly inhibit polyamine-induced increases in the discharge frequency.
      Polyamines inhibited direct depolarizations induced by the glutamate agonists
      NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in a
      concentration and time dependent manner. The data are consistent with two sites
      of action for polyamines, one enhancing the frequency of NMDA-mediated
      spontaneous epileptiform discharges and the other inhibiting direct glutamate
      responses in rat cortex. The slow onset (time to maximal enhancement or
      inhibition by polyamines greater than 30 min) and lack of reversibility with
      polyamine removal suggest that these sites are intracellular and/or presynaptic.

PMID- 7507577
TI  - Nitric oxide (NO) synthase inhibitors abolish cocaine-induced toxicity in mice.
AB  - Repeated administration of cocaine (45 mg/kg/day) for 7 days to Swiss-Webster
      mice resulted in a progressive increase in the convulsive response to cocaine and
      augmentation in lethality rate. Pretreatment with the nitric oxide (NO) synthase
      inhibitors, L-NAME (100 mg/kg/day) or NO-Arg (25 mg/kg/day), prior to cocaine
      administration completely abolished the sensitization to the convulsive and
      lethal responses to cocaine. These findings suggest a role for NO in cocaine
      induced toxicity.

PMID- 7507578
TI  - Evaluation of nefopam as a monoamine uptake inhibitor in vivo in mice.
AB  - Nefopam antagonized 6-hydroxydopamine-induced depletion of heart norepinephrine
      in mice with an ED50 value of 12 mg/kg. Nefopam was ineffective in antagonizing p
      chloroamphetamine-induced depletion of brain serotonin in our standard assay in
      mice, apparently due to a short duration of action. Brain concentrations of the
      serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were decreased after a
      32 mg/kg, i.p., dose of nefopam at 1 and 2 hr but not at 4 hr. When nefopam was
      injected simultaneously with p-chloroamphetamine, it prevented brain serotonin
      depletion initially, but by 6 hr the protective effect was essentially lost,
      suggesting that p-chloroamphetamine persisted in mouse brain longer than did
      nefopam. Nefopam caused a dose-related antagonism of brain serotonin depletion at
      2 hr after injection of a low dose of p-chloroamphetamine hydrochloride (10
      mg/kg, i.p.), with a calculated ED50 value of 11 mg/kg. The lowering of brain 5
      HIAA concentration 2 hr after nefopam injection occurred after a 32 mg/kg dose
      but not after a 3 or 10 mg/kg dose. These data suggest that nefopam is effective
      as an inhibitor of norepinephrine and serotonin uptake at doses previously shown
      to be analgesic in mice, consistent with uptake inhibition being a postulated
      mechanism important in its analgesic effect. Nonetheless, nefopam is a relatively
      weak inhibitor of monoamine uptake with a short duration of action in mice.

PMID- 7507579
TI  - Mechanical instability of Pick bodies and their isolation in an intact form using
      urea solution.
AB  - Isolation of Pick bodies was attempted from an autopsied brain of a patient with
      Pick's disease following a modified method for isolation of senile plaques cores
      and neurofibrillary tangles in the brains of Alzheimer's disease. Pick bodies
      were mechanically less stable than senile plaque cores and neurofibrillary
      tangles since Pick bodies were destroyed by vigorous homogenization or treatment
      with 1% sodium dodecyl sulfate solution. Pick bodies were released out of mother
      neuronal cells in an intact form by treatment with 8 M urea solution for several
      hours at room temperature. Finally, fine structure of Pick filaments released
      from Pick bodies was compared with the filaments of neurofibrillary tangles.

PMID- 7507580
TI  - ATP- and acetylcholine-activated channels co-existing in cell-free membrane
      patches from rat sympathetic neuron.
AB  - The interaction between ATP-activated channels and the nicotinic receptor
      channels has been reported in neuronal cells. To elucidate the mechanisms
      underlying the interaction, the currents activated by ATP and acetylcholine (ACh)
      were recorded from cell-free membrane patches excised from rat sympathetic
      neurons. When ATP or ACh (30-300 microM) was applied, the current consisting of
      multiple channels was observed in most outside-out patches. The amplitude of the
      ATP-activated current and that of the ACh-activated current in the same patches
      were highly correlated (r = 0.89). In a part of the patches, the current
      activated by ACh (300 microM) with ATP (300 microM) was smaller than the current
      successively activated by ACh alone, indicating that ATP did not add the current
      but rather inhibited the ACh-activated channels. In addition, the decay of the
      current activated by ACh with ATP was faster than the current activated by ACh
      alone. The coexistence of the two types of channels in the same patches and the
      interaction of ATP with the ACh-activated current in the cell-free condition may
      support our previous hypothesis, namely, the activation by ATP of a subpopulation
      of the nicotinic receptor-channels.

PMID- 7507582
TI  - Hepatitis C virus seroprevalence in patients attending a sexual health centre.
AB  - AIM: To determine the prevalence of hepatitis C virus (HCV) infection in patients
      attending the Christchurch sexual health centre. METHODS: Anonymised unlinked
      serum specimens from 362 patients sequentially attending the sexual health centre
      were obtained and tested for HCV antibody using the second generation enzyme
      immunoassay kit (Abbott). Antibody positive samples were assayed for virus by
      amplification of hepatitis C ribonucleic acid (RNA). RESULTS: Twelve patients
      (3.3%) were seropositive and 10 samples were also positive for virus RNA (2.7%).
      In 50% of cases the patients had no discernible risk factors other than
      unprotected sexual intercourse. An overall serum prevalence of 22% (4/19) was
      noted within a sub population who admitted to intravenous drug use. Ninety
      patients had, at the time of consultation, requested an antibody test for the
      human immunodeficiency virus (HIV). There were no antibodies to HIV detected in
      any of these patients nor any statistical difference in HCV antibody prevalence
      within this group. CONCLUSION: Hepatitis C is a common viral infection within the
      community. A significant percentage of patients who were anti HCV positive had no
      discernible risk factors other than sexual transmission which must be considered
      as a mode of transmission. We concur with the Department of Health guidelines
      emphasising the need for safer sex practices in a patient with a diagnosis of
      hepatitis C.

PMID- 7507583
TI  - [A morphological study of the keratin cytoskeleton of the oocyte from the clawed
      toad using heterologous monoclonal antibodies].
AB  - Heterologous monoclonal antibodies E2 (against rat cytokeratin 8) and OSC-1
      (against cytoskeletal preparations of mouse oocytes) were used to study the
      presence and distribution of cytokeratins in Xenopus oocytes during their
      maturation and growth. To improve visualization of cytokeratins, more adequate
      methods of oocyte fixation and processing were developed. The results on
      distribution of cytokeratins obtained with the above mentioned antibodies were
      compared with one another and with published data. It was found that data
      obtained by different authors, who used different types of antibodies and
      different methods for fixation and visualization of Xenopus oocyte cytokeratins,
      are often contradictory and inconsistent. Along with that, common features of
      cytokeratin distribution are revealed that have been noticed by every author:
      animal-vegetal asymmetry of cytokeratin distribution and the existence of two
      keratin domains, cortical and ooplasmic ones. Specific for the cortical domain of
      the animal hemisphere is the arrangement of filaments in parallels to the
      surface, whereas filaments of the ooplasmic domain are oriented radially. The
      vegetal hemisphere is characterized by the presence of a network formed by
      filaments with different orientation. We also describe certain peculiarities of
      cytokeratin distribution in previtellogenic oocytes, as well as disintegration of
      the keratin system by the end of oocyte maturation.

PMID- 7507584
TI  - [Combination of high dose after-loading radiation therapy and percutaneous
      irradiation in the management of tumors of the major airways].
AB  - 17 patients with malignant main airway tumours were treated with combined high
      dose rate afterloading and external beam irradiation. The improvement of the
      general conditions of the patients and that of the leading symptoms (dyspnoe,
      cough) were observed in all cases. First experiences corresponding with those of
      others suggest that this method should be integrated routinely in the management
      of main airway malignancies with endoluminal exophytic involvement.

PMID- 7507581
TI  - Hepatitis C seroprevalence in bone marrow transplant recipients and
      haemophiliacs.
AB  - AIM: To determine the prevalence of antibodies to hepatitis C (anti-HCV) in
      patients who have undergone bone marrow transplantation in Wellington, prior to
      the introduction of hepatitis C screening, and to contrast these results with the
      prevalence of anti-HCV in the Wellington haemophiliac population. METHOD: Serum
      specimens were obtained from 30 patients who had undergone bone marrow
      transplantation for the treatment of haematological disorders, and from 29
      haemophiliacs. Specimens were analysed using a second generation HCV immunoassay.
      RESULTS: Exposure to blood products was high in bone marrow transplant recipients
      with subjects receiving red cells or platelets from an average of 53 donors
      (range 15-100, SD 23.2) during their transplant procedure. Despite the high usage
      of blood products, only one of the 30 patients tested was positive for hepatitis
      C on the basis of second-generation antibody testing. Confirmatory testing in
      this patient, (anti-HCV immunoblot assay) was negative. In contrast, 26 of 29
      (89%) haemophiliac patients tested were positive for anti-HCV. CONCLUSION:
      Although the infective risk of blood products cannot be underestimated, the risk
      of patients contracting hepatitis C from multiple single-unit transfusions, prior
      to the introduction of screening for hepatitis C was low. This contrasts with the
      high risk of hepatitis C seroconversion in patients exposed to pooled plasma
      products.

PMID- 7507585
TI  - Chronic pain in the spinal cord injured: statistical approach and pharmacological
      treatment.
AB  - We include in this article the results of a postal inquiry into chronic pain in
      SCI patients in Valencia (Spain), and our experience with their management. A
      mailed questionnaire including lesion and chronic pain data was sent to all of
      the 380 SCI patients who live in the region of Valencia. We received 202 answers,
      with 145 questionnaires being accurately answered and these were analysed for
      this study. The results show that chronic pain (that is, lasting more than 6
      months) is very common (65.5%). The most frequent type was deafferentation pain
      (phantom pain), described as burning or a painful numbness. Since 1988 we have
      been treating a sample of 33 patients suffering from resistant pain according to
      the following therapies: 1 amitriptyline + clonazepam+NSAID (nonsteroidal
      antiinflammatory drugs); 2 amitriptyline + clonazepam + 5-OH-tryptophane + TENS
      (transcutaneous electrical nerve stimulation); 3 amitriptyline + clonazepam + SCS
      (spinal cord stimulation); 4 morphine, by continuous intrathecal infusion. After
      almost 4 years using these therapies we can affirm that the results regarding
      analgesia reached 80% in all cases, and that morphine used by intrathecal route
      is very safe and useful in selected patients.

PMID- 7507586
TI  - External stimuli and intracellular signalling in the modification of the nematode
      surface during transition to the mammalian host environment.
AB  - Previous work has shown that the surface of infective larvae of parasitic
      nematodes will not bind the fluorescent lipid analogue 5-N
      (octadecanoyl)aminofluorescein (AF18) until after exposure of the parasite to
      mammalian tissue-culture conditions. In this study, culture media which are
      permissive or non-permissive for the acquisition of lipophilicity for AF18 were
      altered in order to examine possible stimuli involved. This showed that external
      alkaline pH and high sodium ion concentration were highly stimulatory. The
      internal signalling pathways which may be involved in the surface alteration were
      then examined using agents which are known to affect intracellular signalling in
      mammalian cells. The results indicated that elevation of cGMP levels was
      stimulatory whereas inhibition of a putative Na+/H+ antiporter or calcium
      mobilization was inhibitory, and it is argued that high intracellular levels of
      cAMP may be inhibitory. Whilst the precise effects of the agents used on nematode
      cells remain to be established, these results provide a framework for the
      examination of the processes involved in the modification of the nematode surface
      which takes place immediately after the infection event.

PMID- 7507587
TI  - Antiplatelet granule membrane protein (GMP-140) autoantibodies detected in plasma
      from patients with idiopathic thrombocytopenic purpura.
AB  - Plasma from 92 patients with idiopathic thrombocytopenic purpura (ITP) was tested
      for autoantibodies against granule membrane protein 140 (GMP-140) using an
      antigen specific immunoassay. Results showed that autoantibodies to GMP-140
      existed in 17 of these patients (18.5%). Incubation of patient plasma with
      purified GMP-140, immobilized on nitrocellulose strips by SDS-PAGE and Western
      blotting, revealed a staining band at the level of GMP-140 in two of 8 plasmas.
      Autoantibodies to GMP-140 often coexisted with other autoantibodies, in
      particular towards GP Ib/IX (3 cases), GP IIb-IIIa (5 cases) or both (3 cases).
      This study provides direct evidence for the presence of anti-platelet GMP-140
      autoantibodies in some patients with ITP.

PMID- 7507588
TI  - The pharmacology of alpha-adrenergic decongestants.
AB  - The mechanism by which decongestants produce their action is activation of
      postjunctional alpha-adrenergic receptors found on precapillary and postcapillary
      blood vessels of the nasal mucosa. Activation of these receptors by either direct
      binding of the sympathomimetic agent to the binding site of the receptor, or by
      the enhanced release of norepinephrine produces vasoconstriction. Such
      vasoconstriction decreases blood flow through the nasal mucosa and results in
      shrinkage of this tissue. Decongestants can be administered topically, directly
      onto the nasal mucosa, or orally. Prolonged topical administration may produce
      rebound congestion. Oral decongestants can affect the cardiovascular, urinary,
      central nervous, and endocrine systems. Overdose can produce medically
      significant increases in blood pressure as well as central nervous system
      stimulation.

PMID- 7507590
TI  - Selecting a decongestant.
AB  - Antihistamines and decongestants often are used interchangeably and in
      combination for a variety of upper respiratory illnesses ranging from allergic
      rhinitis to the common cold; yet, these two classes of drugs have distinct
      therapeutic actions. When administered alone, antihistamines are of no value in
      reducing nasal stuffiness. Therefore, many allergy products also contain
      decongestants. Conversely, cough-cold remedies often contain antihistamines
      despite their lack of efficacy in these conditions. Nasal congestion, on the
      other hand, regardless of its cause, responds quite well to decongestants. The
      topical route provides a faster and more intense decrease in nasal airway
      resistance, but has a shorter duration and the potential to produce rebound
      congestion in patients with allergic rhinitis, whereas oral agents do not.
      Phenylpropanolamine, pseudoephedrine, and phenylephrine are the most common
      decongestants. Although all are sympathomimetic amines, their efficacy varies. In
      particular, phenylephrine is subject to first-pass metabolism and therefore is
      not bioavailable in currently recommended doses. In addition, phenylpropanolamine
      and pseudoephedrine, but not phenylephrine, are effective decongestants. Slow
      release formulations allow a longer dosing interval, especially during the night.
      However, most formulations available in the United States are manufactured and
      sold without Food and Drug Administration scrutiny. Since the in vitro
      dissolution of many of these products differs, it is possible that some of the
      generic formulations are not bioequivalent to established brand-name products.
      Therefore, pharmacists should not substitute formulations without discussing the
      matter with the prescriber.

PMID- 7507589
TI  - Pharmacokinetics of oral decongestants.
AB  - Only three drugs are commonly used as oral decongestants--phenylpropanolamine
      (PPA), pseudoephedrine (PDE), and phenylephrine (PE). They are all chiral drugs
      that exist as stereoisomers. It is possible that each enantiomer can reflect
      significant enantioselective differences with regard to both pharmacokinetic and
      pharmacodynamic effects. Both PPA and PDE are readily and completely absorbed,
      whereas PE, with a bioavailability of only approximately 38%, is subject to gut
      wall metabolism and is thought to be absorbed erratically. Peak concentrations
      are reached between 0.5 and 2 hours after administration. All three drugs are
      extensively distributed into extravascular sites (apparent volume of distribution
      between 2.6 and 5.0 L/kg). No protein-binding data in humans are available.
      Whereas PPA and PDE are not substantially metabolized, PE undergoes extensive
      biotransformation in the gut wall and the liver. Elimination of PPA and PDE is
      predominantly renal, with urinary excretion being pH dependent. Half-lives are
      relatively short, approximately 2.5 hours for PE, 4 hours for PPA, and 6 hours
      for PDE. Elimination of PPA and PDE may be rapid in children, and the agents
      should be used with caution in patients with renal impairment. In addition, PPA
      increases caffeine plasma levels and decreases theophylline clearance. Reduced
      metabolism of PE occurs with concurrent administration of monoamine oxidase
      inhibitors. No direct relationship between nasal decongestant effect and plasma
      concentration has been established.

PMID- 7507591
TI  - Pharmaco-legal considerations in the clinical use of decongestants.
AB  - Thanks to changes in the health care environment, pharmacists are no longer
      viewed as merely dispensers of pharmaceuticals. They are now required to render
      judgments concerning patient therapy based on legal mandates directed at
      accuracy, efficiency, and quality of care. Moreover, pharmacists' decisions and
      actions are governed by legal requirements for patient counseling, drug therapy
      monitoring, and drug substitution. A number of these requirements stem from the
      federal Omnibus Budget Reconciliation Act of 1990 legislation relating to
      Medicaid, which mandates expanded responsibilities for pharmacists. For the past
      decade, however, state regulations have governed risk-assessment and risk
      management responsibilities with regard to physicians and pharmacists. The
      original antisubstitution laws, which were exceptionally restrictive, have been
      replaced by newer regulations clearly defining pharmacists' legal
      responsibilities regarding drug substitution. These regulations address patient
      consent, cost savings, Orange Book standards, and delayed-release dosage forms.
      All of them have considerable impact on the dispensing of decongestants by
      pharmacists.

PMID- 7507592
TI  - [Immunologic characteristics of monoclonal antibodies to Mycobacterium Bovis and
      four affinity-purified mycobacterial antigens].
AB  - Monoclonal antibodies to M. bovis were obtained and characterized. Affinity
      purified mycobacterial antigens were isolated from tuberculin PPD using these
      antibodies. Comparative immunochemical analysis of four antigens was carried out.
      Sufficient differences between the antigens were observed in both ELISA and
      tuberculin skin tests on guinea pigs. Serologically specific for M. bovis 3-1C
      antigen was shown to express cross-reacting T-epitopes, in contrast to another
      specific antigen isolated earlier in the same way using rabbit polyclonal
      antibodies against tuberculin PPD. None of the specific mycobacterial antigens
      isolated was immunodominant in the serodiagnostic test for tuberculosis.

PMID- 7507593
TI  - Effect of recombinant human colony-stimulating factor on the course of
      parasitaemia in non-lethal rodent malaria.
AB  - The effect of repeated subcutaneous injections of recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) on the attenuated Plasmodium berghei XAT
      infection in CBA mice was examined. When mice were injected with rhG-CSF daily
      beginning 2 days before infection, the neutrophil count in the peripheral blood
      increased 5 times higher than that of control mice and the development of
      parasitaemia was suppressed significantly during the early phase of the
      infection. This suppressive effect of rhG-CSF was reduced by treatment of the
      mice with either anti-interferon (IFN)-gamma or anti-tumour necrosis factor (TNF)
      alpha immunoglobulins. These results suggest that neutrophils may have a role in
      immunity against the parasites and that IFN-gamma and TNF-alpha are possibly
      involved.

PMID- 7507594
TI  - AF64A (ethylcholine mustard aziridinium) impairs acquisition and performance of a
      spatial, but not a cued water maze task: relation to cholinergic hypofunction.
AB  - The cholinergic neurotoxin AF64A (ethylcholine mustard aziridinium) produced
      alterations in a spatial but not a nonspatial cognitive task following ICV
      injection. AF64A impaired acquisition and performance in the standard Morris
      water maze task, evidenced by significantly longer latencies to find the
      submerged platform. However, the AF64A group exhibited shorter latencies and more
      direct paths to the target at the end of training, which suggests acquisition of
      efficient search strategies and a sparing of procedural memory. However, the
      AF64A group spent significantly less time in the target quadrant during the probe
      trial than the CSF group. This suggests a failure to learn the specific location
      of the target and impaired declarative memory processes. In contrast, AF64A did
      not affect performance of a cued MWM task that did not involve spatial memory
      processing, demonstrating the absence of motoric, sensory, or motivational
      impairments. The AF64A-induced behavioral deficits were associated with a) a
      significant decrease in high affinity choline transport (HAChT), b) reduced
      concentrations of 5-HT and 5-HIAA, and c) an increased ratio of 5-HIAA/5HT, in
      the HPC. There were no changes in choline uptake in the gustatory cortex, the
      amygdala, or the striatum. Percent time in the target quadrant during the probe
      trial was significantly correlated with HAChT in the HPC. There were no
      correlations between any of the behavioral measures and HAChT in the striatum,
      gustatory cortex, or the amygdala, or between serotonergic or noradrenergic
      parameters in the HPC. These data suggest that AF64A produces cognitive deficits
      in spatial tasks that are correlated with the cholinergic hypofunction induced by
      the compound.

PMID- 7507595
TI  - [Cholinergic action of Bay K-8644 on the rat heart sinus node automaticity].
AB  - The actions of different concentrations of a dihydropyridine agonist (Bay K-8644)
      on rat heart sinus node automaticity and their interactions with atropine, were
      studied. The experiments were performed using a portion of the right atrium that
      contained the sinus node, perfused with Tyrode's solution at 37 degrees C and
      registering the action potentials with intracellular microelectrodes (Ag-KCL).
      The series of Bay K with or without atropine were perfused during 10 min.
      Atropine, 1 x 10(-5) M, did not change sinus frequency after 30 min of perfusion
      (237 +/- 6 to 229 +/- 7 action potentials/min; n = 24). Bay K, 2.8 x 10(-8) M (10
      ug/L) did not change sinus frequency (240 +/- 9 to 246 +/- 12; n = 8, but in the
      presence of atropine, caused an increment (225 +/- 7 to 256 +/- 12 p < 0.05). Bay
      K, 7 x 10(-8) M (25 ug/L) and 1.4 x 10(-7) M (50 ug/L, caused an increase in
      sinus frequency (237 +/- 5 to 279 +/- 15; n = 9 p < 0.05 and 254 +/- 6 to 291 +/-
      6; n = 6 p < 0.05 respectively) that occurred sooner in the presence of atropine.
      It is concluded that Bay-K has a cholinergic effect that interferes with its
      positive chronotropic action, specially at low concentrations.

PMID- 7507596
TI  - [Hyperthyroidism].
AB  - Hyperthyroidism may result from excessive synthesis for thyroid hormones, from
      leaking of stored hormones in inflammatory thyroid disease, or from the
      inappropriate ingestion of thyroid hormones or iodine containing drugs. An
      overview of the clinical picture and the different types of hyperthyroidism as
      well as the various approaches used in the diagnostic work-up and in the therapy
      of hyperthyroidism is presented.

PMID- 7507597
TI  - Germline-encoded IgG antibodies bind mouse cartilage in vivo: epitope- and
      idiotype-specific binding and inhibition.
AB  - Autoantibodies specific for type-II collagen (CII) occur in mice and rats with
      collagen-induced arthritis (CIA). The binding in vitro and in vivo of mouse
      monoclonal antibodies (MoAbs) specific for separate epitopes in CII have been
      investigated. Two-day-old mice were injected intraperitoneally (i.p.) with the
      anti-CII antibody CIID3 in both unlabelled and biotinylated form. It was found
      that antibodies binding to the same epitope in CII in vivo can inhibit others
      from binding in an epitope-specific fashion. The binding in vivo and in vitro of
      anti-CII antibodies could be inhibited also by an anti-idiotypic rat antiserum
      produced against the D3 antibody. The anti-idiotypic antiserum inhibited the
      binding of the antibody D3 and the idiotypically related antibody C2. The cDNA's
      of anti-CII antibodies D3, C2, and F4 were sequenced and found to contain
      germline encoded V-genes, apparently without somatic mutations. The variable
      heavy chain of D3 and C2 both expressed the same VH rearrangement, confirming
      that they share idiotypes. This report demonstrates that CII-specific germline
      encoded IgG autoantibodies bind specifically to normal cartilage in vivo via
      their combining site.

PMID- 7507598
TI  - Human NK cells expressing alpha 4 beta 1/beta 7 adhere to VCAM-1 without
      preactivation.
AB  - The authors demonstrate that resting CD56+/CD3- NK cell adhesion to the
      endothelial VCAM-1 is over three-fold higher than CD56-/CD3+ T-cell adhesion. T
      cell, but not NK-cell adhesion, to VCAM-1 is enhanced significantly by
      stimulation. The expression of VCAM-1 receptor subunits alpha 4 and beta 1 on
      both effector cells remains unchanged upon stimulation. A subpopulation of NK
      cells, as well as of T cells, was found to express beta 7, whose expression was
      not altered upon stimulation. The authors conclude that the adhesive properties
      of the same receptor structures on these distinct cell populations are regulated
      in a different manner, according to the specific functions of the effector cells
      of the immune system.

PMID- 7507599
TI  - Population dynamics of CD4+ T cells lacking Thy-1 in murine retrovirus-induced
      immunodeficiency syndrome (MAIDS).
AB  - Increased numbers of CD4+ Thy-1- cells have been described in the spleen (SP) of
      mice with retrovirus-induced immunodeficiency (MAIDS). Since this phenotypic
      abnormality might have considerable functional importance, the expansion of the
      CD4+ Thy-1- subset in MAIDS was characterized further. CD4+ Thy-1- and Thy-1+ T
      cells from infected mice expressed similar densities of CD3 and TCR alpha/beta.
      In contrast, the Thy-1- subset was uniformly CD44hi, even early in the disease
      when part of Thy-1+ cells were still CD44lo. The emergence of CD4+ Thy-1- cells
      occurred first in SP and lymph nodes and was observed later in thymus. The
      important fraction of CD4+ cells lacking Thy-1 normally present in Peyer's
      patches was only weakly modified. Despite the major expansion of the CD4+ Thy-1-
      phenotype, the proliferating fraction was not higher in this subset than in CD4+
      Thy-1+ cells from infected mice. Persistence after hydroxyurea administration was
      identical in both subsets, indicating similar mean cell lifespans. Taken
      together, these results show that the major expansion of CD4+ Thy-1- T-cells in
      MAIDS is not ascribable solely to increased proliferation within this subset.
      Phenotypic analysis suggests that CD4+ Thy-1- cells result from the
      differentiation of Thy-1+ cells induced by activation signals related to
      retroviral infection.

PMID- 7507600
TI  - [3-line response following long-term therapy of severe aplastic anemia using
      glycosylated rHuG-CSF: dysfunctional thrombocytes as early indication of a
      myelodysplastic syndrome].
AB  - We report on a patient with very severe aplastic anemia (SAA) unresponsive to
      immunosuppressive therapy (cyclosporine A, ATG). Because no HLA-identical family
      or unrelated donor could be found, a trial with recombinant human granulocyte
      stimulating factor (G-CSF) was started. This was followed by a rapid 3-lineage
      response with near-normal blood counts and transfusion independence. A similar
      response was obtained by 2 further G-CSF cycles which were given for relapsing
      SAA after G-CSF withdrawal. Following the third cycle, an acquired platelet
      function disorder was observed which preceded a myelodysplastic syndrome.

PMID- 7507601
TI  - Elderly men with cancer: social work interventions in prostate cancer.
AB  - Prostate cancer requires the attention of social workers in health care for three
      reasons: the growing elderly population which will increase the number diagnosed,
      the recent introduction of new treatments and the lack of social acceptability
      for this condition. Interventions for prostate cancer are specific to the stage
      of the disease. These individual, family and group interventions are a model for
      social work services to elderly men with other forms of cancer. Social workers
      have opportunity to research quality of life and decision-making issues to
      enhance medical practise in prostate cancer.

PMID- 7507602
TI  - [The interferon status in diabetes mellitus].
AB  - The investigation of interferon status in 54 diabetes mellitus patients gave
      evidence for high levels of blood serum interferon, leukocyte inhibition of alpha
      interferon production against moderate synthesis of gamma interferon. More marked
      alterations in the interferon status were registered in severe insulin-dependent
      diabetes mellitus complicated by angiopathies and running more than 5 years.
      Compensation of metabolic processes was not relevant to interferon status.
      Variations in the levels of alpha- and gamma-interferons in the course ob
      observation occurred in 30% of the patients.

PMID- 7507603
TI  - [The beneficial action of Navoban during antineoplastic chemotherapy].

PMID- 7507604
TI  - [Ring chromosome 21 as a cause of developmental disorder. A case report from the
      practice of child psychiatry].
AB  - Ring chromosome 21 is a very rare chromosomal abnormality known to cause a great
      variety of clinical findings. Persons with ring chromosome 21 can be
      intellectually and phenotypically normal, but this abnormality is found more
      often in persons with dysmorphic features, malformations and mental retardation.
      Ring chromosome 21 is also encountered as the only chromosomal abnormality in
      individuals with Down syndrome. We describe a four year old girl with ring
      chromosome 21 (karyotype 46,XX/46,XX,-21, +r(21)), who was examined in a
      department of child psychiatry because of delayed development. The child had
      serious speech and language problems, slightly dysmorphic features and bilateral
      hip-joint dysplasia.

PMID- 7507605
TI  - Behavior of embryonic chick heart cells in culture. 2. Cellular responses to
      epidermal growth factor and other growth signals.
AB  - Muscle cell-enriched primary cell cultures were prepared from 8-day embryonic
      chick heart ventricles (74% of these cells showed positive staining with anti
      cardiac myosin antibody). To determine if Epidermal Growth Factor (EGF) affects
      cardiac muscle cells, immunostaining and autoradiography were performed to find
      the Muscle Cell Labeling Index (MLI). MLI represents the proportion of cardiac
      myosin-positive cells that specifically incorporated [3H]thymidine. The MLI for
      EGF-treated cells was 51%. Controls in Serum-free Nutrient Medium (SFNM) had a
      MLI of 34.5%. Combinations of growth signals also were tested. EGF, IGF-I
      (Insulin-like Growth Factor-I), or PDGF (Platelet-derived Growth Factor) alone
      increased [3H]thymidine incorporation in the cells. Adding IGF-I or PDGF
      simultaneously with EGF enhanced the response of the cells to EGF by increasing
      [3H]thymidine incorporation. TGF-beta (Transforming Growth Factor-beta) alone was
      shown to have an inhibitory effect on [3H]thymidine incorporation, and when TGF
      beta was added together with EGF, it attenuated the stimulatory effect of EGF on
      [3H]thymidine incorporation. Phorbol 12-Myristate 13-Acetate (PMA), a tumor
      promoter, alone had no effect on [3H]thymidine incorporation, but its addition
      suppressed the stimulatory effect of EGF when they were added simultaneously in
      the presence of 5% FBS. Developmental response of the heart cells to growth
      signals also was tested. Heart cells from 18-day embryos were used to test the
      effect of insulin and EGF. Although both insulin and EGF increased [3H]thymidine
      incorporation in heart cells from 8-day embryos, different responses to insulin
      and EGF occurred with heart cells from 18-day embryos. Whereas the heart cells
      from 18-day embryos still responded to EGF by increasing [3H]thymidine
      incorporation, they did not show a response to insulin as measured by
      [3H]thymidine incorporation, suggesting that the loss of response of the heart
      cells to growth signals may occur at the receptor level. Further studies show
      that EGF, TGF-alpha, aFGF, and PDGF increased the total numbers of heart cells,
      and that aFGF and PDGF also increased the percentages of heart muscle cells.

PMID- 7507606
TI  - High level of hepatitis C endemicity in Gabon, equatorial Africa.
AB  - To assess the prevalence of hepatitis C virus (HCV) infection, a community-based
      study was performed in eastern Gabon on 1172 subjects over 5 years of age. The
      prevalence of antibodies to HCV (anti-HCV) detected using second-generation
      enzyme-linked immunosorbent assay (ELISA) and confirmed by an immunoblot assay
      (RIBA 2), was 6.5%. Anti-HCV prevalence increased with age but was related to
      neither sex nor ethnic group. Among 30 subjects with positive ELISA results, 14
      had HCV viraemia as shown by the polymerase chain reaction (11/12 RIBA positive,
      2/15 RIBA negative, 1/3 RIBA indeterminate). We conclude that HCV is highly
      endemic in western equatorial Africa and that a high proportion of the population
      may be viraemic.

PMID- 7507607
TI  - Prevalence of hepatitis C antibodies in patient groups in Egypt.

PMID- 7507608
TI  - Rapid staining and mounting of concentrated, intestinal protozoan parasites from
      MIF-preserved specimens.

PMID- 7507609
TI  - Prion protein: a different concept of replication.

PMID- 7507610
TI  - 'Memories are made of this'.

PMID- 7507611
TI  - Receiver psychology and the design of animal signals.
AB  - Animal communication is studied both by neurobiologists and by evolutionary
      biologists, but in very different ways. The purpose of this article is to show
      how both groups could benefit from a greater appreciation of each other's
      approach. Evolutionary biologists should take more account of the role played by
      the sensory systems and brains of receivers in constraining the design of animal
      signals. Neurobiologists should be more aware of recent advances in the
      understanding of signal-receiver co-evolution and the evolutionary origins of
      animal signals. A series of recent examples are cited that illustrate how pre
      existing neurophysiological or psychological properties of receiver organisms are
      essential to our understanding of the design characteristics of animal signals
      and of their origins. Also discussed are a number of other areas of signalling in
      which the study of 'receiver psychology' is likely to be fruitful.

PMID- 7507612
TI  - The Human Brain Project: an international resource.
AB  - As the amount of basic neuroscientific information increases dramatically, its
      day-to-day integration and application becomes an increasing difficulty.
      Technological advances, particularly in computer and information sciences, should
      allow this information 'explosion' to become more manageable. To this end, the
      Human Brain Project, an initiative of several NIH Institutes and other United
      States Government agencies, is being developed to provide a computer database
      that will allow neuroscientists access to information at all levels of
      integration, from genes to behavior. In this article Michael Huerta, Stephen
      Koslow and Alan Leshner outline the genesis and ideas behind the initiative and
      discuss its future development.

PMID- 7507613
TI  - A radical hypothesis for neurodegeneration.
AB  - Point mutations in the cytosolic Cu/Zn superoxide dismutase (SOD-1) gene have
      been detected in association with familial amyotrophic lateral sclerosis (FALS).
      SOD clears superoxide radical and is one of the body's principal defense
      mechanisms against oxygen toxicity. The finding of SOD variants in FALS is
      consistent with the hypothesis that free radicals contribute to the pathogenesis
      of FALS, and possibly to the pathogenesis of other neurodegenerative disorders
      such as Parkinson's disease, in which there is substantial evidence of oxidant
      stress. The implication of free radicals in the pathogenesis of neurodegenerative
      disorders raises the possibility that antioxidants might provide neuroprotective
      therapy.

PMID- 7507614
TI  - Cognitive and language functions of the human cerebellum.
AB  - Traditionally, the human cerebellum has been regarded as a motor mechanism, but
      this view of its function is being challenged by a growing body of data on the
      non-motor functions of the cerebellum. Some of these data are presented in this
      article, which reviews neuroanatomical, neuroimaging and behavioral reports of
      cerebellar involvement in cognitive and language functions. The article proposes
      that this functional expansion is a consequence of specific cerebellar structural
      changes that evolved during hominid evolution and that could have been a
      prerequisite for the evolution of human language.

PMID- 7507615
TI  - Movement and thought: identical control mechanisms by the cerebellum.

PMID- 7507616
TI  - Motor skills but not cognitive tasks.

PMID- 7507617
TI  - 'Involvement in' versus 'storage of'.

PMID- 7507618
TI  - Na+ currents that fail to inactivate.
AB  - Textbook accounts give the impression that Na+ channels are short-acting binary
      switches: depolarization opens them, but only for about one millisecond. In
      contrast to this simplified view, a small but significant fraction of the total
      Na+ current in neurons occurs because channels open after long delays or in long
      duration bursts of openings. Such non-inactivating Na+ current acts
      physiologically in neurons to amplify synaptic potentials and enhance endogenous
      rhythmicity, and also to aid repetitive firing of action potentials. In glial
      cells it also may regulate Na(+)-K+ ATPase activity. The evidence for non
      inactivating Na+ current in a variety of neurons and glia is reviewed, along with
      a brief discussion of its ion channel substrate and its relevance for
      neurological diseases and drug therapy.

PMID- 7507619
TI  - Tau protein and the neurofibrillary pathology of Alzheimer's disease.
AB  - Abundant neurofibrillary tangles, neuropil threads and senile plaque neurites
      constitute the neurofibrillary pathology of Alzheimer's disease. They form in the
      nerve cells that undergo degeneration in the disease, in which their regional
      distribution correlates with the degree of dementia. Each lesion contains the
      paired helical filament (PHF) as its major fibrous component. Recent work has
      shown that PHFs are composed of the microtubule-associated protein tau in an
      abnormally phosphorylated state. PHF-tau is hyperphosphorylated on all six adult
      brain isoforms. As a consequence, tau is unable to bind to microtubules and is
      believed to self-assemble into the PHF. Current evidence suggests that protein
      kinases or protein phosphatases with a specificity for serine/threonine-proline
      residues are involved in the abnormal phosphorylation of tau.

PMID- 7507620
TI  - Cytoskeleton dynamics during neurotransmitter release.
AB  - It has become apparent in recent years that the cytoskeleton and its associated
      proteins play a major role in secretion. This review summarizes recent findings
      on the cytoskeleton organization and the molecular topology of its regulatory
      proteins, as well as the dynamic changes that occur in this organelle during
      secretion from neurons and secretory cells. Although two apparently different
      ultrastructures and molecular organizations of the cytoskeleton seem to be
      involved in neuronal and secretory cell secretion, there are similarities between
      the two systems. In both neurons and secretory cells, Ca2+ plays a pivotal role
      in the control of cytoskeleton dynamics, especially in the changes in actin
      filament networks observed during secretion.

PMID- 7507621
TI  - Expression patterns of homeobox and other putative regulatory genes in the
      embryonic mouse forebrain suggest a neuromeric organization.
AB  - The molecular mechanisms that control regional specification, morphogenesis and
      differentiation of the embryonic forebrain are not known, although recently
      several laboratories have isolated homeobox, Wnt and other genes that are
      candidates for playing roles in these processes. Most of these genes exhibit
      temporally and spatially restricted patterns of expression within the forebrain.
      However, analysis of the spatial patterns has been complicated because an
      understanding of the organization of the embryonic forebrain has been lacking.
      This article describes a neuromeric model of the forebrain that is consistent
      with the expression patterns of these genes, and that provides a framework for
      understanding the morphological relationships within this complex structure.

PMID- 7507623
TI  - Peptide sequences with strong stimulatory activity for lymphoid cells:
      implications for vaccine development.
AB  - Seven peptides derived from the bacterial major outer-membrane protein TraT were
      synthesized and then tested in lymphoproliferative assays using lymphoid cells
      from a variety of animals that had been immunized with the native TraT molecule
      in saline. A hierarchical pattern of responsiveness to the peptides was observed
      in the four animal species studied and in particular three of the peptides (T2,
      T4 and T6) showed very strong responses in all species. The 'universality' of the
      TraT-derived peptides was confirmed by studying the responsiveness of lymphoid
      cells obtained from the peripheral blood of twenty clinically normal human
      donors. Thus, following a secondary in vitro immunization with TraT-pulsed human
      peripheral blood mononuclear cells, responsiveness to TraT and to the TraT
      derived peptides was observed in the cultures derived from all twenty donors.
      Taken together, our findings imply that the putative T-cell epitope peptides (T2,
      T4 and T6) could be employed as carriers in subunit vaccines and thereby help to
      overcome the unresponsiveness observed in animals and humans as a result of MHC
      restriction.

PMID- 7507622
TI  - Long-term depression of excitatory synaptic transmission and its relationship to
      long-term potentiation.
AB  - In many brain areas, including the cerebellar cortex, neocortex, hippocampus,
      striatum and nucleus accumbens, brief activation of an excitatory pathway can
      produce long-term depression (LTD) of synaptic transmission. In most
      preparations, induction of LTD has been shown to require a minimum level of
      postsynaptic depolarization and a rise in the intracellular Ca2+ concentration
      [Ca2+]i in the postsynaptic neurone. Thus, induction conditions resemble those
      described for the initiation of associative long-term potentiation (LTP).
      However, data from structures susceptible to both LTD and LTP suggest that a
      stronger depolarization and a greater increase in [Ca2+]i are required to induce
      LTP than to initiate LTD. The source of Ca2+ appears to be less critical for the
      differential induction of LTP and LTD than the amplitude of the Ca2+ surge, since
      the activation of voltage- and ligand-gated Ca2+ conductances as well as the
      release from intracellular stores have all been shown to contribute to both LTD
      and LTP induction. LTD is induceable even at inactive synapses if [Ca2+]i is
      raised to the appropriate level by antidromic or heterosynaptic activation, or by
      raising the extracellular Ca2+ concentration [Ca2+]o. These conditions suggest a
      rule (called here the ABS rule) for activity-dependent synaptic modifications
      that differs from the classical Hebb rule and that can account for both
      homosynaptic LTD and LTP as well as for heterosynaptic competition and
      associativity.

PMID- 7507624
TI  - Induction of cytolytic and antibody responses using Plasmodium falciparum
      repeatless circumsporozoite protein encapsulated in liposomes.
AB  - Plasmodium circumsporozoite (CS) protein-induced antibody and T-cell responses
      are considered to be important in protective immunity. Since the key repeat
      determinant of the CS protein may actually restrict the recognition of other
      potential T- and B-cell sites, a modified Plasmodium falciparum CS protein
      lacking the central repeat region, RLF, was expressed in Escherichia coli. On
      purification, RLF was encapsulated into liposomes [L(RLF)] and used for the in
      vivo induction of cytolytic T lymphocytes (CTL) and antibodies. Immunization of
      B10.Br (H-2k) mice with L(RLF), but not with RLF, induced CD8+ CTL specific for
      the P. falciparum CS protein CTL epitope, amino acid residues 368-390. Anti
      L(RLF) serum reacted with antigens on intact sporozoites and inhibited sporozoite
      invasion of hepatoma cells. Antibody specificity studies in New Zealand White
      rabbits revealed new B-cell sites localized in amino acid residues 84-94, 91-99,
      97-106 and 367-375. Although the mechanisms by which liposomes enhance cellular
      and humoral immune responses remain unknown, liposome-formulated vaccines have
      been well tolerated in humans; hence, their use in vaccines, when efficacy
      depends on antibody and CTL responses, may be broadly applicable.

PMID- 7507625
TI  - Passively transferred antibodies directed against conserved regions of SIV
      envelope protect macaques from SIV infection.
AB  - Inactivated plasma collected from either SIV-infected or peptide-vaccinated
      macaques was transferred into 17 naive rhesus monkeys. Two additional macaques
      received normal plasma and served as controls. Following transfer all 19 monkeys
      were inoculated with SIV. While the controls became infected and were virus
      isolation-positive, 3 of 6 recipients of SIV peptide vaccine plasma and 9 of 11
      recipients of SIV-infected monkey plasma were protected. None of the 12 protected
      animals became virus-isolation-positive or seroconverted within 100 days of
      follow-up. One, however was SIV-PCR-positive. All 12 protected animals were
      rechallenged 100 days after the initial inoculation; 8 became infected and
      yielded virus as expected, but 4 remained uninfected. One of the latter was the
      SIV-PCR-positive monkey mentioned above, suggesting that cryptic SIV infection
      may be of significance in immunological protection. The results demonstrate that
      envelope anti-peptide antibodies have similar protective potential in vivo as
      antibodies directed to the whole virus. In vitro neutralization competition
      assays performed with sera from vaccinated macaques in the presence of the free
      peptides suggest that of the four conserved envelope peptides of the vaccine, the
      two originating from gp41 rather than the two from gp120 are responsible for
      inducing the neutralizing anti-syncytial activity.

PMID- 7507626
TI  - [Doppler ultrasound studies of breast tumors with the continuous wave technique].
AB  - The aim of the study was to ascertain the reliability of continuous-wave Doppler
      signals in the diagnosis of breast cancer. CW-Doppler findings in a series of 63
      cases of palpable breast tumors with histologic confirmation (24 malignancies and
      39 benign tumors) are reported. Depending on the parameters used -20 -24 of 24
      malignant nodes (83%-100%) and 20 -24 of 39 benign lesions (51%-62%) were
      correctly identified. Even benign tumors showed significant differences in
      systolic peak and diastolic frequencies compared to the contralateral breast. The
      Resistance-Index (RI) did not allow the differentiation of lesions when measured
      on one side only. Comparing the Resistance-Indices of both breasts helped
      improving the specificity of CW-Doppler-sonography to 89.7% and the positive
      predictive value to 73.3%. The CW-Doppler-sonography with the relevant parameters
      of diastolic and systolic peak frequency and the RI is considered a useful tool
      in the diagnosis of breast cancer.

PMID- 7507627
TI  - [Aging and cerebral representation of language].
AB  - Some characteristics of acquired aphasias during adulthood--frequency, severity,
      type of aphasia--would change with aging. In particular, Wernicke's aphasia
      patients are repeatedly reported to be older than Broca's. Several hypotheses are
      proposed to account for these age-related changes. One of the explanations puts
      forward hypothetical changes in the neural substrate with aging. A second
      hypothesis refers to the involvement of cognitive and behavioral changes
      occurring in elderly. A third one claims that changes in functional distribution
      of language in brain (between hemispheres and within left hemisphere) may occur
      with aging.

PMID- 7507628
TI  - Characterization of anti-myeloperoxidase antibodies in vasculitis.
AB  - Anti-myeloperoxidase (MPO) antibodies are frequently encountered in patients with
      vasculitis. Using a competitive inhibition ELISA test and immunoblotting, we
      suggest that anti-MPO antibodies might represent a heterogenous group of auto
      antibodies directed against different conformational epitopes of MPO molecule.

PMID- 7507629
TI  - Pathogenetic aspects of autoantibodies to endothelial cells in systemic
      vasculitis.

PMID- 7507630
TI  - Increased expression of CD25 and adhesion molecules on peripheral blood
      lymphocytes of patients with Wegener's granulomatosis (WG) and ANCA positive
      vasculitides.
AB  - Peripheral blood lymphocytes of 29 c-ANCA positive WG patients fulfilling the ACR
      classification criteria were examined for the expression of various leukocyte
      surface molecules by dual marker cytofluorometry (FACStar, Becton Dickinson).
      Activation markers such as CD25, HLA-DR, CD29 and adhesion molecules (ICAM-1 and
      LFA-3) were clearly elevated in this group in comparison to 40 healthy
      volunteers. Similar results were obtained for p-ANCA positives vasculitides (n =
      13) and, unexpectedly, also for patients suffering from cholesteatoma, a chronic,
      bacterial infection of the middle ear (n = 21). The results are discussed in view
      of a pathogenic model for WG and vasculitic disorders.

PMID- 7507632
TI  - Self-retaining intraurethral device for treatment of prostatic obstruction.
AB  - We report our experience about insertion of 32 self-retaining intraurethral
      device (IUC) in patients with prostatic obstruction. Follow-up ranged between 2
      and 38 weeks. Success rate of IUC insertion was 93.7% and 46.6% of patients have
      IUC in place without complications during follow-up. IUC is easy and quick to
      introduce, it allows spontaneous voiding, full continence, sexual activity and
      routine life-style. It represents a useful alternative to indwelling catheter in
      patients at high risk or refusing surgery and it might be used in patients who
      are waiting for surgery or need long term catheterization.

PMID- 7507633
TI  - [Voluminous recurrence of benign prostatic hypertrophy].

PMID- 7507631
TI  - Antineutrophil cytoplasmic autoantibodies (ANCA) recognizing a recombinant
      myeloperoxidase subunit.
AB  - Sera from 76 patients with diverse vasculitis, systemic lupus erythematosus (SLE)
      and hydralazine-induced lupus (HiL) were analysed by ELISA for their reactivity
      with native, reduced or urea-denatured MPO, respectively, as well as with
      bacterially expressed heavy and light subunits of MPO. All sera (n = 20)
      recognizing native MPO showed a positive reaction with reduced MPO, while 12
      recognized the denatured protein. Most of the linear epitopes are located in the
      light subunit, since 9 MPO-positive sera recognized significantly the bacterially
      expressed, denatured light subunit, while only one serum recognized the
      bacterially expressed heavy subunit purified under denaturing conditions.

PMID- 7507634
TI  - [Prostatic cancer between 50 and 60. A more than 20-year-long retrospective
      study. Apropos of 65 case reports].
AB  - Sixty five 50 to 60 year old patients have been treated for prostatic cancer over
      a 21 year period. Twenty four had a local prostatic cancer (A1, A2, B1, B2) and
      41 (63.2%) a locally advanced or metastatic (D1, D2 disease at diagnosis. The
      mean age was 56 years old. As being as retrospective study, miscellaneous
      treatments were done. The 5 and 10 years survival, analysed with the Kaplan-Meier
      method, was 61% and 31% respectively. According to the stage of cancer, the 10
      year survival was 72% and 5% for (A-B) and (C-D) respectively. For well
      differentiated tumors, 5 years survival was 67% instead of 36% for
      undifferentiated ones. The 10 year survival was 36% for well differentiated
      tumors with 6 on 8 patients who survived with a mean of 11.6 ears. The authors
      discussed the benefit of an early diagnosis of prostatic in the 50-60 year old
      men group which is 4% of the total prostatic cancer diagnosed within the same
      period. They analysed the influence of PSA and transrectal sonography interest at
      this age.

PMID- 7507635
TI  - Facilitation of reentry by lidocaine in canine myocardial infarction.
AB  - The authors studied the effects of lidocaine in 18 consecutive dogs with
      myocardial infarction 1 to 4 days after two-stage left anterior descending
      coronary artery ligation. Electrophysiologic testing was performed in
      anesthetized dogs after infarction with single-, double-, or triple-programmed
      extrastimuli or rapid bursts (3 beats at 240 to 420 beats/min) delivered to the
      right ventricular outflow tract. Inducibility of sustained monomorphic
      ventricular tachycardia after an intravenous bolus of lidocaine (3 to 6 mg/kg)
      was compared in the same animal to the premedicated state. In the control state,
      sustained monomorphic ventricular tachycardia was inducible in 6 of 18 dogs.
      After administration of lidocaine, electrically induced sustained monomorphic
      ventricular tachycardia was initiated in an additional nine dogs (which were
      previously noninducible; after lidocaine administration vs control p < 0.02). The
      antiarrhythmic agent induced further rate-dependent slowing of conduction in the
      periinfarction subepicardium, which at a critical value of rate and amount of
      conduction delay resulted in sustained reentrant monomorphic tachycardia. These
      results show that lidocaine has marked proarrhythmic action in this canine model
      of myocardial infarction, probably because of its depressant effect on injured
      cardiac tissue.

PMID- 7507636
TI  - Atrial arrhythmias in athletes.

PMID- 7507637
TI  - Continuous electrocardiographic monitoring for more than one hour does not
      improve the prognostic value of ventricular arrhythmias in survivors of first
      acute myocardial infarction.
AB  - This study was designed to compare the prognostic value of predischarge
      ambulatory electrocardiographic monitoring for 1, 6 and 24 hours in 188 patients
      surviving a first acute myocardial infarction. Ventricular premature complexes
      (VPCs) were considered as a mean hourly rate or classified using Lown and Moss
      grading systems. During the 1-year follow-up 20 cardiac deaths occurred. For all
      3 monitoring times, a higher number of VPCs/hour and a higher Moss grade were
      associated with mortality, whereas a Lown grading system gave prognostic
      information only for the first hour of recording. Monitoring time did not
      influence specificity or sensitivity in predicting mortality; > or = 3 VPCs/hour
      showed a higher sensitivity than > or = 10 VPCs/hour (p < 0.05) with a comparable
      specificity. After 1-hour data entered the model, neither the 6- or the 24-hour
      data entry improved the overall likelihood ratio statistic, regardless of what
      VPC grading system was used. These results demonstrate that continuous
      electrocardiographic recordings of > 1 hour are unnecessary when they are to be
      used for detecting ventricular arrhythmia as a predictor of mortality in patients
      surviving a first acute myocardial infarction.

PMID- 7507638
TI  - Effects of diltiazem, metoprolol, enalapril and hydrochlorothiazide on frequency
      of ventricular premature complexes.
AB  - Ventricular arrhythmias occur frequently in patients with hypertensive left
      ventricular (LV) hypertrophy and have been associated with increased incidence of
      sudden death. In this study, the effect of various antihypertensive medications
      on ventricular arrhythmias was evaluated in 31 hypertensive patients with
      moderate to severe LV hypertrophy. Patients were assessed at baseline (after 3
      weeks of placebo treatment) and after treatment with each of 4 monotherapies:
      diltiazem 120 or 240 mg/day, metoprolol 100 or 200 mg/day, enalapril 10 or 20
      mg/day and hydrochlorothiazide 50 or 100 mg/day. Each drug therapy was
      administered for 4 weeks. The sequence of each treatment was determined at
      random. Echocardiographic measurements and electrocardiograms were obtained only
      at baseline. Biochemical measurements and 48-hour Holter monitoring were obtained
      at baseline and at the end of each treatment. All treatments resulted in a
      significant but similar decrease in blood pressure. In the group as a whole
      diltiazem decreased ventricular premature complexes (VPCs) by 65% (p < 0.05) and
      metoprolol by 52% (p = 0.07). Enalapril and hydrochlorothiazide had no effect. In
      12 patients with > or = 5 VPCs/hour at baseline, diltiazem and metoprolol
      decreased VPCs by 66% (p < 0.05). It is concluded that in hypertensive patients
      with moderate to severe LV hypertrophy, both diltiazem and metoprolol
      significantly reduce VPCs.

PMID- 7507639
TI  - Re: Risk factors for benign prostatic hypertrophy.

PMID- 7507640
TI  - Pentosan polysulfate-induced thrombocytopenia and thrombosis.
AB  - Pentosan polysulfate is a low-molecular-weight sulfated polysaccharide used as an
      antithrombotic drug. We present two patients who developed thrombocytopenia and
      venous thrombosis during treatment with pentosan polysulfate. The relationship
      between pentosan polysulfate and thrombocytopenia is supported by platelet
      aggregation and serotonin release tests. In the light of the literature and our
      two cases, it appears that pentosan polysulfate alone as standard heparin and low
      molecular-weight heparin can induce thrombocytopenia and thrombosis. Platelet
      counts should therefore be periodically monitored during pentosan polysulfate
      treatment. In the case of pentosan polysulfate-induced thrombocytopenia, it seems
      that heparin or low-molecular-weight heparin should not be instituted during the
      acute phase even if platelet aggregation studies are negative, because of their
      low sensitivity. After remission of thrombocytopenia, whether or not
      glycosaminoglycans can be reinstituted, at least temporarily, after antibody had
      disappeared is still an open question.

PMID- 7507641
TI  - Mild beta+(-87)-thalassemia CACCC box mutation is associated with elevated fetal
      hemoglobin expression in cis.
AB  - The beta zero-thalassemia codon 39 nonsense mutation predominant in Sardinia is
      severe, and homozygotes are transfusion dependent. Two-thirds of beta zero 39
      alleles are linked to A gamma T (haplotype II). One-fourth are linked to A gamma
      I (haplotypes I and IX), as is the mild beta +-thalassemia -87 C-->G mutation
      (haplotype VIII). beta +/beta zero-Thalassemia VIII/II compound heterozygotes
      have significantly higher A gamma I:A gamma T (23:7) than beta zero-thalassemia
      I/II (24:20) or IX/II (16:17) cases. This suggests that the beta + -87 mutation
      is associated with elevated gamma expression in cis, which may contribute to the
      lack of transfusion-dependence in beta +/beta zero cases.

PMID- 7507642
TI  - Leishman's stain, a Romanowsky stain suboptimal for demonstration of Auer rods.

PMID- 7507643
TI  - Ultrasonographic investigation of placental morphologic characteristics and size
      during the second trimester of pregnancy.
AB  - OBJECTIVE: The aim of the study was to establish the incidence of abnormal
      placental ultrasonographic findings in an unselected obstetric population and
      determine the usefulness of simple measurements of placental size. In addition,
      the relationship between these findings, uterine artery Doppler measurements,
      maternal serum alpha-fetoprotein levels, and subsequent pregnancy outcome was
      explored. STUDY DESIGN: A prospective, cross-sectional study of 210 women
      recruited at the time of routine ultrasonographic scan between 16 and 28 weeks'
      gestation was performed. Placental ultrasonographic investigations included
      measurements of thickness, circumference, and volume and morphologic studies.
      Uterine Doppler and maternal serum alpha-fetoprotein measurements were performed
      at the same time. RESULTS: At delivery 25 fetuses were small for gestational age,
      in association with hypertension in 11; 14 were delivered prematurely but were
      appropriately grown, and three were macrosomic. Significant correlations were
      found in uncomplicated pregnancies (n = 168) between gestational age and
      placental thickness, circumference, and volume and also between fetal abdominal
      and placental circumferences. Large sonolucent lakes were found with a similar
      incidence in both complicated and uncomplicated pregnancies. Jelly-like placental
      appearance was seen in 12 of the 17 cases complicated by hypertension, 11 of
      which also had abnormal uterine Doppler features and elevated maternal serum
      alpha-fetoprotein levels. CONCLUSIONS: This study shows an association between
      abnormal placental development, ultrasonographic appearances, and subsequent
      abnormal fetal growth or hypertensive disorders of pregnancy. The
      interrelationships demonstrated between the different techniques suggest that a
      combination of placental thickness and morphologic characteristics, uterine
      Doppler analysis, and evaluation of maternal serum alpha-fetoprotein level may
      allow more efficient screening for these complications than is currently possible
      using any single method.

PMID- 7507645
TI  - An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the
      uterus and inhibits contractility during pregnancy.
AB  - OBJECTIVE: Nitric oxide is synthesized from L-arginine and it causes relaxation
      of smooth muscle by elevating cyclic guanosine monophosphate levels. We
      hypothesized that an L-arginine-nitric oxide-cGMP system is present in the uterus
      and modulates contractility. STUDY DESIGN: Isometric tension of the uterus was
      measured in vitro from pregnant rats in response to various agents that modulate
      nitric oxide-cyclic guanosine monophosphate production or action. RESULTS: Major
      findings are as follows: (1) The substrate and a donor of nitric oxide produced
      uterine relaxation; (2) inhibitors of the nitric oxide-cyclic guanosine
      monophosphate pathway blocked the relaxation responses; (3) nitric oxide synthase
      was localized to several uterine cell types; (4) nitric oxide was produced by the
      uterus during periods when L-arginine was consumed and citrulline levels
      increased; (5) effects of nitric oxide substrate on relaxation were mimicked by
      cyclic guanosine monophosphate; (6) nitric oxide-cyclic guanosine monophosphate
      responses were decreased during delivery; (7) L-arginine responses were increased
      by progesterone, and antiprogesterone treatment decreased cyclic guanosine
      monophosphate-induced relaxations. CONCLUSION: An L-arginine-nitric oxide-cyclic
      guanosine monophosphate system is present in the uterus and it may regulate
      relaxation during pregnancy. The inhibitory action of L-arginine and 8-bromo
      cyclic guanosine monophosphate was considerably lower during delivery and post
      partum, indicating that the nitric oxide system may contribute to the maintenance
      of uterine quiescence during pregnancy, when progesterone levels are elevated,
      but not during delivery.

PMID- 7507644
TI  - Hormonal regulation of complement components and receptors throughout the
      menstrual cycle.
AB  - OBJECTIVES: Complement components have been recently demonstrated to be present
      in the reproductive tract. Among these components, C3 synthesis by glandular
      epithelium of the rat uterus has been shown to be regulated by estrogen;
      progesterone inhibits this synthesis. However, the hormonal regulation of C3 and
      the presence of other complement factors in the human has not been investigated
      to date. In this study we examined the presence and the hormonal regulation of
      different complement components and receptors in the human endometrium at various
      phases of the menstrual cycle of normally cycling women with no pelvic pathologic
      abnormalities. STUDY DESIGN: Endometrial tissue was obtained from normally
      cycling women, and immunohistochemistry was performed by means of monoclonal
      antibodies against C3, factors B, decay-accelerating factor, membrane cofactor
      protein, and complement receptor types 1, 2, and 3. The tissue was incubated with
      minimal essential media without methionine containing methionine labeled with
      sulfur 35. Immunoprecipitations were performed on the media with goat antihuman
      C3 antibody, and the proteins were analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. RESULTS: C3 was found to be present in the
      glandular epithelial cells of luteal endometrium. Biosynthesis as analyzed by
      immunoprecipitation with anti-C3 antibody was found to increase during the luteal
      phase of the cycle and to be minimal in the proliferative phase. Like C3, factor
      B and decay-accelerating factor were localized to the luteal glandular epithelial
      cells. In contrast, membrane cofactor protein was found to be present in the
      glandular epithelium throughout the menstrual cycle, and complement receptor type
      1 was present only in the stromal compartment of luteal endometrium. Complement
      receptor type 3 was present only in the infiltrating leukocytes in the luteal
      endometrium, whereas complement receptor type 2 was undetectable. CONCLUSIONS:
      These findings suggest that several components of the complement system exist in
      the human endometrium in a hormone-dependent manner and may play a role in normal
      reproductive function.

PMID- 7507647
TI  - Effects of otitis media on child development.
AB  - Otitis media is one of the most common diseases of childhood, and the broad
      continuum of this disease ranges from asymptomatic middle ear effusion to
      recurring or persistent infection. In spite of many modalities of successful
      treatment, there remains a large number of children with chronic otitis media
      after antibiotic management and even in some persistent cases after surgical
      management with ventilation and tube insertion. This report attempts to concisely
      review the studies on the effect of otitis media on childhood development.

PMID- 7507646
TI  - Very low maternal serum chorionic gonadotropin levels in association with fetal
      triploidy.
AB  - OBJECTIVE: The objective of this study was to identify the parental origin of the
      extra haploid set of chromosomes in triploid pregnancies and to correlate the
      parental origin to very low levels of human chorionic gonadotropin and
      unconjugated estriol levels (multiple of the median < or = 0.20) and normal alpha
      fetoprotein levels. STUDY DESIGN: Three triploid pregnancies were ascertained
      retrospectively, and three pregnancies were identified prospectively. Maternal
      sera samples were analyzed for levels of alpha-fetoprotein, human chorionic
      gonadotropin, and unconjugated estriol. Deoxyribonucleic acid analysis was
      performed on parental bloods and fetal fibroblasts in two prospectively
      identified pregnancies to establish the parental origin of the extra set of
      chromosomes. RESULTS: Levels of alpha-fetoprotein were normal in all pregnancies.
      Levels of human chorionic gonadotropin were very low in five of six of
      pregnancies, and unconjugated estriol levels were low in three of six
      pregnancies. Deoxyribonucleic acid analysis indicated maternal origin of the
      extra haploid set of chromosomes in two triploids. CONCLUSION: When the extra
      haploid set of chromosomes are maternally derived, some triploid pregnancies
      exhibit very low levels of maternal serum human chorionic gonadotropin and
      unconjugated estriol with normal levels of alpha-fetoprotein.

PMID- 7507649
TI  - Quantitative reverse transcriptase-polymerase chain reaction of glucose
      transporter 1 mRNA levels in rat brain microvessels.
AB  - We investigated the usefulness of reverse transcriptase-polymerase chain reaction
      (RT-PCR) to quantify glucose transporter 1 (GLUT1) mRNA in cerebral microvessels.
      The technique was validated using an in vitro-transcribed RNA fragment
      (riboprobe) of partial 3' noncoding sequence of rat brain GLUT1 gene. A known
      amount of the riboprobe was reverse-transcribed to cDNA (target DNA). PCR primers
      were made to amplify a 292-bp fragment of the target DNA. The 5' primer was end
      labeled with 32P. An oligonucleotide of 100 bp containing the same sequences as
      the first 30 and the last 70 bases of the 292-bp fragment of the target DNA was
      synthesized and used as competitive DNA. The target DNA was coamplified with
      increasing amounts of competitive DNA using the same two primers. The ratio of
      radioactivity between amplified products of the target DNA (292-bp fragment) and
      the competitive DNA (100-bp fragment) was determined quantitatively after
      separation by gel electrophoresis and radioactivity counting. This method gave an
      accurate estimation of the amount of the riboprobe in the reaction and a 2- to 5
      fold change in the amounts could be detected. By this method, the mean amount of
      GLUT1 mRNA from purified rat brain microvessels was estimated to be 1.5 +/- 0.1 x
      10(-6) ng/ng total RNA. This value was about 10-fold higher than that in rat cell
      line PC12.

PMID- 7507650
TI  - Quantitation of changes in the expression of multiple genes by simultaneous
      polymerase chain reaction.
AB  - We developed a reverse transcription-polymerase chain reaction (RT-PCR) method
      which permits the simultaneous amplification of several mRNAs, even though their
      relative levels may be very different. First-strand cDNAs were synthesized from
      total RNA by MMLV reverse transcriptase with oligo(dT)15 priming. Analysis was
      performed in the linear phase of PCR, allowing the detection of the products by
      polyacrylamide gel electrophoresis followed by ethidium bromide staining. In
      order to obtain a similar amplification of multiple targets in the same PCR
      system, it was necessary: (i) to adjust the relative concentration of each set of
      primers and (ii) to use high-stringency conditions (annealing temperature and
      addition of organic solvent). These conditions allowed the rapid quantitation of
      several mRNAs in multiple samples, minimizing experimental variations. The
      reliability of the method was established by measuring variations of c-Ki-Ras,
      ornithine decarboxylase, alpha-amylase, and beta-actin mRNA levels during the
      growth of pancreatic tumoral AR4-2J cells. Glyceraldehyde-6-phosphate
      dehydrogenase expression showed very small variations which confirm that it
      represents a reliable internal standard for studies of gene expression. Results
      from competitive PCR amplification of target cDNA and internal competitive
      template were in agreement with those of simultaneous amplification, validating
      the quantitative aspect of the method.

PMID- 7507651
TI  - RNA-RNA in situ hybridization using digoxigenin-labeled probes: the use of high
      molecular-weight polyvinyl alcohol in the alkaline phosphatase indoxyl-nitroblue
      tetrazolium reaction.
AB  - A nonradioactive RNA-RNA in situ hybridization method using digoxigenin-labeled
      probes is described. The visualization of hybrids is done using the indoxyl-nitro
      blue tetrazolium alkaline phosphatase reaction. The addition of polyvinyl
      alcohols of high molecular weight (40-100 kDa) to the reaction medium enhances
      the alkaline phosphatase reaction and prevents diffusion of reaction
      intermediates, resulting in a 20-fold increase in sensitivity without increasing
      the background. Due to the more localized precipitation of the formazan, the site
      of hybridization can be determined more precisely.

PMID- 7507653
TI  - The effect of maltose tetrapalmitate (MTP) on prostate cancer growth in vivo and
      in vitro.
AB  - Maltose tetrapalmitate (MTP), a non-toxic synthetic glycolipid analog of lipid A,
      has been shown to have antitumor activity in tumor-transplanted animals. Its mode
      of action has been postulated to be as an immunoadjuvant or as an anti
      angiogenesis agent. MTP has been shown to have antitumor properties in lung,
      bladder, mammary, colon, liver and soft tissue tumors, but its action on prostate
      cancer has not yet been investigated. The effect of MTP alone and in combination
      with hydrocortisone hemisuccinate on prostate cancer and the ability of MTP to
      inhibit angiogenesis were examined in this study. In vitro, MTP was minimally
      cytotoxic to rat prostate cancer cells and to bovine and human endothelial cells
      at high concentrations. In the angiogenesis inhibition assays, the MTP alone
      exhibited no anti-angiogenesis effect and significant anti-angiogenesis activity
      only when combined with hydrocortisone hemisuccinate at high doses. In vivo,
      however, MTP demonstrated significant inhibition of prostate cancer growth. These
      results suggest that MTP decreases prostate cancer growth in vivo but it is not
      an angiogenesis inhibitor in rat prostate cancer.

PMID- 7507648
TI  - Emotional and behavioral problems and severe academic delays among sheltered
      homeless children in Los Angeles County.
AB  - OBJECTIVES: Few studies have estimated the extent of specific emotional,
      behavioral, and academic problems among sheltered homeless children. The
      objectives of this study were to describe such problems, identify those children
      with the problems, and evaluate the relationship between child problems and use
      of physical and mental health services. METHODS: From February through May 1991,
      169 school-age children and their parents living in 18 emergency homeless family
      shelters in Los Angeles County were interviewed. To evaluate the answers,
      interviewers used standardized measures of depression, behavioral problems,
      receptive vocabulary, and reading. RESULTS: The vast majority (78%) of homeless
      children suffered from either depression, a behavioral problem, or severe
      academic delay. Among children having a problem, only one third of the parents
      were aware of any problem, and few of those children (15%) had ever received
      mental health care or special education. CONCLUSIONS: Almost all school-age
      sheltered homeless children in Los Angeles County have symptoms of depression, a
      behavioral problem, or academic delay severe enough to merit a clinical
      evaluation, yet few receive specific care. Programs targeted at sheltered
      homeless school-age children are needed to close this gap.

PMID- 7507652
TI  - 186Rhenium-HNK1 monoclonal antibody targets human small cell lung cancer cells in
      athymic nude mice: rapid screening model for therapy.
AB  - A model is described by which in vivo tumor-MOAB interactions may be
      investigated. The method is rapid and may aid in the selection of appropriate
      MOABS from a panel of MOABS for individualized patient treatment. Groups of
      athymic nude mice were injected intravenously with small cell lung cancer line
      SHP-77 cells which are trapped primarily in the lungs. Twenty-four hours post
      tumor cell inoculation, 186Rhenium tagged HNK1 MOAB (CD57) was injected
      intravenously. Controls which received no tumor cells were injected with unbound
      186Re or radioactive MOAB. Biodistribution studies at 24 hours following MOAB
      injection showed significantly more radioactivity in lungs of mice inoculated
      with both SHP-77 cells and 186Re MOAB than did lungs of controls.

PMID- 7507654
TI  - Response of the FSaII fibrosarcoma to antiangiogenic modulators plus cytotoxic
      agents.
AB  - The formation of a blood supply (angiogenesis) is critical to the growth of solid
      tumors. The naturally occurring steroid tetrahydrocortisol, the synthetic
      cyclodextrin derivative beta-cyclodextrin tetradecasulfate, and the tetracycline
      derivative minocycline have antiangiogenic activity. Tetrahydrocortisol (125
      mg/kg) and beta-cyclodextrin tetradecasulfate (1000 mg/kg) in a 1:1 molar ratio
      by continuous infusion over 14 days and minocycline (10 mg/kg) administered i.p.
      daily from day 4 to day 18 postimplantation of the FSaII fibrosarcoma did not
      alter the growth of the tumor. These antiangiogenic modulators were not cytotoxic
      toward FSaIIC tumor cells or bone marrow CFU-GM when tumor-bearing animals were
      treated and cytotoxicity determined by colony formation in culture. The
      antiangiogenic modulators markedly increased the cytotoxicity of cyclophosphamide
      toward FSaIIC tumor cells and to a much lesser degree toward bone marrow CFU-GM.
      The cytotoxicity of CDDP and radiation was enhanced only by administration of the
      three modulators in combination. In tumor growth delay studies, the three
      modulator combination increased the effectiveness of CDDP by 1.5-fold, of
      cyclophosphamide by 1.9-fold and of radiation by 1.4-fold. Although the
      antiangiogenic therapies alone did not substantially reduce the number of lung
      metastases compared with the untreated controls, addition of the antiangiogenic
      agents to treatment with the cytotoxic therapies reduced not only the number of
      lung metastases formed from the primary tumor but also reduced the number of
      large metastases. Thus, antiangiogenic therapies can potentiate the efficacy of
      standard anticancer therapies.

PMID- 7507655
TI  - Pentosan inhibits angiogenesis in vitro and suppresses prostate tumor growth in
      vivo.
AB  - Pentosan polysulfate (PPS) is a highly negatively charged polysaccharide which
      has activity against multiple tumor types in the preclinical setting. We
      demonstrate here that Pentosan inhibits the growth of the anaplastic Dunning
      R3327 rat prostate adenocarcinoma MAT-LyLu when treatment was started when the
      tumor was not palpable but has little effect against established tumors. This
      inhibition may be mediated by the effect of Pentosan on endothelial cells.
      Pentosan, in combination with hydrocortisone, inhibits endothelial cell motility
      and tubule formation in vitro and inhibits capillary formation in the chicken
      chorioallantoic membrane (CAM) assay. These data suggest that Pentosan may be a
      potent inhibitor of tumor-associated angiogenesis and may be an effective agent
      for the prevention and/or suppression of prostate cancer growth.

PMID- 7507656
TI  - Guidelines for the application of surgery and endoprostheses in the palliation of
      obstructive jaundice in advanced cancer of the pancreas.
AB  - OBJECTIVE: This study was set up to identify patient-related factors favoring the
      application of either surgery or endoprostheses in the palliation of obstructive
      jaundice in subsets of patients with cancer of the head of the pancreas or
      periampullary region. SUMMARY BACKGROUND DATA: In the palliation of obstructive
      jaundice, surgical biliodigestive anastomosis has traditionally been performed.
      Surgical biliary bypass is associated with high mortality (15% to 30%) and
      morbidity rates (20% to 60%) but little recurrent obstructive jaundice (0% to
      15%). Biliary drainage with endoscopically placed endoprostheses has a lower
      complication rate, but recurrent obstructive jaundice is seen in up to 20% to 50%
      of patients. METHODS: Patients with advanced cancer of the head of the pancreas
      or periampullary region treated at the University Hospital Dijkzigt, Rotterdam,
      The Netherlands, between 1980 and 1990 were reviewed. In 148 patients, data were
      compared concerning the morbidity and hospital stay after the palliation of
      obstructive jaundice with endoscopic endoprostheses or surgical biliary bypasses.
      These patients were stratified for long (> 6 months) and short (< 6 months)
      survival times. RESULTS: In short-term survivors, the higher late morbidity rates
      after endoprostheses were offset by higher early morbidity rates and longer
      hospital stays after the surgical bypass. In long-term survivors, there was no
      difference in the hospital stay between the two groups, but the late morbidity
      rate was significantly higher in the endoprosthesis group. CONCLUSIONS: These
      data suggest that endoscopic endoprosthesis is the optimal palliation for
      patients surviving less than 6 months and surgical biliary bypass for those
      surviving more than 6 months. This policy necessitates the development of
      prognostic criteria, which were obtained by Cox proportional-hazards survival
      analysis. Advanced age, male sex, liver metastases, and large diameters of tumors
      were unfavorable prognostic factors. With these factors, the risk of short- or
      long-term survival can be predicted. It is hoped that the application of these
      data may allow a rational approach toward optimal palliative treatment of this
      form of malignant obstructive jaundice.

PMID- 7507657
TI  - Efficacy of rapamycin and FK 506 in prolonging rat hind limb allograft survival.
AB  - OBJECTIVE: Graft rejection and the toxicity of current immunosuppressive regimens
      preclude the application of microsurgical advances to transplantation of limbs or
      other nonessential parts. If limb transplantation is to become a clinical
      reality, newer, safer, more effective immunosuppressive agents are needed.
      SUMMARY BACKGROUND DATA: Rapamycin (RPM) and FK 506 are fungal macrolide
      antibiotics with effective immunosuppressive properties demonstrated in several
      animal models. RPM is more potent and effective than is FK 506 in rat cardiac
      allografts and has demonstrated synergy with cyclosporine (CsA) in limb allograft
      models. METHODS: An orthotopic rat hind limb allograft model (Brown-Norway [RT
      1n] to Lewis [RT-1(1)] rats was used. RPM (doses, 3.0, 4.5, and 6.0 mg/kg/day)
      was administered intraperitoneally on postoperative days 1 to 14. FK 506 (6
      mg/kg/day) was administered orally on postoperative 1 to 14 and 1 to 90 and at
      rejection onset (10 mg/kg/day for salvage). CsA with RPM (postoperative days 1 to
      14) was used to assess synergy, with CsA alone serving as the control. Other
      controls included untreated and placebo-treated allografted animals. The
      permutation test and Mann-Whitney test were applied to the data. RESULTS: The
      mean survival times were assessed as follows: (1) control (placebo, untreated), 5
      days; (2) RPM groups, 9.5, 10.6, and 8.7 days; (3) 14-day FK 506, 28 days; (4) 90
      day FK 506, > 90 days; (5) CsA, 17.3 days; and (6) CsA with RPM, 19.3 days. FK
      506 significantly prolonged graft survival compared with RPM (Permutation Test, p
      < 0.001 and Mann-Whitney Test, p < 0.05). FK 506 salvage reversed early
      rejection. High-dose RPM produced significant toxicity. Synergy between CsA and
      RPM was not demonstrated. CONCLUSIONS: FK 506 prolongs allograft survival,
      reverses early rejection, and prevents rejection without clinical toxicity when
      given continually. RPM does not prevent rejection in this model and produces
      significant toxicity at high doses. FK 506 may be a first step in making limb
      transplantation a clinical reality in reconstructive surgery.

PMID- 7507658
TI  - Contributions of the surgical sciences to a reduction of the mortality rate in
      the United States for the period 1968 to 1988.
AB  - OBJECTIVE: The authors sought to determine whether advances in the surgical
      sciences have led to a reduction in mortality rates for diseases treated by
      surgery during the past 25 years. They also wished to study changes in health
      care manpower for perioperative care during this period. SUMMARY BACKGROUND DATA:
      Surgical operations requiring general anesthesia in the United States have risen
      to 25 million per year at an annual cost of approximately $125 billion. During
      the period 1968 to 1988, the number of anesthesiologists per 100,000 persons in
      the United States increased 98%, although the number of surgeons remained
      relatively constant. Between 1980 and 1989, the number of radiologists per
      100,000 persons decreased to 29% below the figure for 1965. Membership in
      specialized nursing societies increased dramatically. METHODS: The authors used
      vital statistics data from the National Center for Health Statistics (NCHS) to
      examine the mortality rates for diseases of the prostate, appendix, and
      gallbladder; hernia and intestinal obstruction; and ulcerative disease of the
      stomach and duodenum for the years 1968, 1978, and 1988. NCHS hospital discharge
      data were used to derive the rates of hospitalization and surgery for these
      conditions. Information on changes in health care manpower was obtained from
      published and other sources. RESULTS: The mortality rates for the five diseases
      studied decreased from 40% to 69% between 1968 and 1978. Between 1978 and 1988,
      the mortality rates caused by benign prostatic hyperplasia declined an additional
      54% and by appendicitis, an additional 43%. Deaths attributable to the other
      conditions remained relatively constant. The rates of hospitalization and surgery
      for these conditions varied. CONCLUSIONS: Advances in surgery, anesthesiology,
      and information transfer and the availability of intensive care units and
      specialized hospital personnel have resulted in reduced mortality rates for
      diseases treated by surgery.

PMID- 7507659
TI  - Stimulation of RNA synthesis in rat parotid lobules by phorbol myristate acetate.
AB  - Incubation of parotid lobules with phorbol 12-myristate 13-acetate (PMA)
      transiently stimulated the incorporation of [3H]uridine into RNA. At 100 nM PMA,
      the rate of RNA synthesis during the first hour was 30% above control rates. The
      Ca2+ ionophore A23187 had no effect on either basal or PMA-stimulated RNA
      synthesis. Stimulation by 100 nM PMA was reversed by the protein kinase C
      inhibitor staurosporin (10 nM). When PMA was added together with isoproterenol or
      okadaic acid, both of which are potent activators of RNA synthesis, the increase
      in RNA synthesis was additive rather than synergistic. The results suggest that
      in the rat parotid gland, protein kinase C induces the rapid transcription of
      certain cellular genes by a mechanism that is independent of the beta-adrenergic
      receptor-activated pathway.

PMID- 7507660
TI  - Simultaneous hybridization and subsequent colour detection of subgingival
      bacterial DNA on colony lifts.
AB  - This paper reports the development of a protocol allowing hybridization and
      detection of DNA fixed to nylon colony lifts from up to three species of bacteria
      simultaneously. Half ml samples of serial dilutions of pure cooked-meat broth
      (CMB) cultures of Capnocytophaga ochracea, Actinobacillus actinomycetemcomitans
      and Prevotella intermedia were grown on trypticase soy blood agar (TSBA) plates
      for 7 days in an anaerobic chamber. From the same CMBs a further set of dilutions
      was completed that contained all three species. Samples from these dilutions
      produced mixed-growth TSBA plates following anaerobic incubation for 7 days.
      After incubation, colony counts on pure-growth TSBA plates were enumerated by
      colony counter. Colony counts of C. ochracea, A. actinomycetemcomitans and P.
      intermedia on mixed-growth TSBA plates were enumerated by nylon colony lift,
      simultaneous hybridization with non-isotopic whole chromosomal DNA probes and
      alkaline phosphatase substrates generating three colours. The results indicate
      that the protocol correctly identified and differentiated between the three
      species on mixed-growth TSBA plates. The proportions of each species and mean
      total colony count expected by counting pure plates were in agreement with the
      proportions of each species and total colony counts enumerated by DNA probes on
      mixed growth plates. The development of simultaneous hybridization and
      multicolour detection will result in improved data recovery from dental plaque
      samples, in addition to reducing the cost and labour required in current colony
      lift protocols, without affecting the specificity or sensitivity of the probes
      used.

PMID- 7507661
TI  - Support of peptide-dependent growth of Bacteroides forsythus by synthetic
      fragments of haemoglobin or fetuin.
AB  - The putative periodontal pathogen Bacteroides forsythus is a fastidious Gram
      negative anaerobe with high proteolytic activity. For growth in a chemically
      defined medium containing insulin it required serum. Serum could be replaced by
      human haemoglobin or bovine asialofetuin, or by proteolytic fragments of these
      two proteins. Four such fragments consisting of from 8 to 18 amino acid residues
      were isolated and sequenced. Only aspartic acid, threonine, and valine were
      common to all peptides. An undecapeptide, Hba11, and a dodecapeptide, AsF12, were
      synthesized and found to be active at micromolar concentrations, but only when
      presented in combination with insulin. An analysis of amino acid requirements
      excluded a direct essential role of peptides as sources of amino acids in
      complete medium, except for valine. Should Bact. forsythus have an essential
      requirement for this amino acid, it could be satisfied by micromolar
      concentrations of peptide but not millimolar concentrations of the free amino
      acid in the absence of peptide. Bact. forsythus could salvage the essential amino
      acids lysine and isoleucine at 100-fold lower concentrations when presented in
      peptide-bound form compared to the free amino acids, and at 10-fold lower
      concentrations of peptide compared to Porphyromonas gingivalis W83, which in
      contrast to Bact. forsythus grew on free amino acids in the absence of insulin
      and peptides.

PMID- 7507662
TI  - Catalytic and ligand binding properties of the FK506 binding protein FKBP12:
      effects of the single amino acid substitution of Tyr82 to Leu.
AB  - The binding of FK506 and rapamycin to their cytosolic receptor FKBP12 is an
      intermediate step in the paths leading to their potent immunosuppressive
      properties. One of the amino acids defining the hydrophobic binding cleft for the
      macrocycles is Tyr82, which is thought to form a hydrogen bond with the amide
      oxygens of the common pipecolyl structural element within the two macrolides. To
      understand better the influence of this amino acid residue in catalytic activity
      (cis-trans peptidyl prolyl isomerization) and ligand binding properties, a Tyr82
      to Leu site-specific modification of FKBP12 was prepared, purified and
      characterized. Kinetic experiments have demonstrated that the Tyr82 to Leu
      modification has a greater effect on catalytic properties than on ligand binding
      affinities, a result which indicates that these inhibitors may not be binding as
      true transition-state analogues. In an additional test for cellular function,
      expression of both wild-type and mutant human FKBP12 in a strain of Saccharomyces
      cerevisiae rendered resistant to rapamycin by deletion of the gene encoding a
      cytosolic rapamycin binding protein (RPB1), the yeast homologue of FKBP12,
      restored wild-type drug sensitivity.

PMID- 7507663
TI  - Detection of circular and linear transcripts of Sry in pre-implantation mouse
      embryos: differences in requirement for reverse transcriptase.
AB  - Sry is the testes determining factor gene located on the Y chromosome. Expression
      of Sry had previously been found to occur during a short time frame of 10.5 to
      12.5 days post coitum in the developing genital ridge. A recent study of the Sry
      transcript from adult testes found that the most abundant transcript is circular
      in nature. We have performed reverse transcription polymerase chain reactions
      with RNA from mouse preimplantation embryos ranging from the 2 cell stage to the
      blastocyst stage and report the detection of both circular and linear forms of
      Sry in the preimplantation embryo. In addition, we also demonstrate that the well
      described reverse transcriptase activity of Taq polymerase leads to a major
      difference in the mode of detection of the two forms.

PMID- 7507666
TI  - Aluminum promotes the aggregation of Alzheimer's amyloid beta-protein in vitro.
AB  - Amyloid beta-protein is the major component of senile plaques in the brains of
      Alzheimer's disease and has an intrinsic tendency to form insoluble aggregates.
      The aggregation of amyloid beta-protein has been suggested to enhance its
      neurotoxicity and to play a key role in the amyloid deposition. Here we show,
      using gel-electrophoresis and immunoblotting, that the aggregation of synthetic
      amyloid beta-protein (beta 1-40) is promoted by aluminum, a suspected risk factor
      in Alzheimer's disease. High molecular weight aggregates were observed, and the
      amount of precipitated protein was estimated using high performance liquid
      chromatography. The results suggest the possibility that aluminum directly
      influences the process of aggregation and the deposition of senile plaques.

PMID- 7507664
TI  - Inducible L-arginine-dependent nitric oxide synthase activity in bovine bone
      marrow-derived macrophages.
AB  - In rodent macrophages, cytokines or bacterial constituents induce a Ca(2+)
      independent nitric oxide (NO) synthase which plays a key role in antimicrobial
      and tumoricidal activity. Firm evidence for expression of a similar enzyme in
      other mammals has been lacking. Here we show that bovine bone marrow-derived
      macrophages produce nitrite in an L-arginine-dependent manner upon stimulation
      with heat-killed gram-positive or gram-negative bacteria. NO2- production was
      markedly diminished by arginase, and by the arginine analogue, NG-monomethyl-L
      arginine. Bacteria-induced NO2- production was enhanced by concomittant exposure
      to interferon-gamma, tumor necrosis factor-alpha or both combined, although these
      cytokines alone (in the absence of bacteria) induced little NO2-. This is one of
      the first demonstrations of NO2- production by non-rodent macrophages.

PMID- 7507665
TI  - Correlation of the insulin receptor substrate-1 with insulin-responsive
      deoxyglucose transport in 3T3-L1 adipocytes.
AB  - We have devised procedures for decreasing the amount of IRS-1 in 3T3-L1
      adipocytes (viz., chronic treatments with insulin, dexamethasone, 1-methyl-3
      isobutylxanthine, cycloheximide or actinomycin D) and have determined the
      correlation between the amounts of IRS-1, insulin receptor, GluT4 and
      phosphatidylinositol 3'-kinase regulatory subunit with insulin-responsive dGlc
      transport. Each of these treatments decreased insulin responsiveness that
      correlated with the amount of IRS-1, but not with the amount of the other
      signaling proteins or tyrosine-phosphorylated IRS-1. Removal of insulin after
      chronic treatment resulted in a return of both insulin responsiveness and IRS-1.
      Increased expression of IRS-1 occurred during differentiation simultaneously with
      increased insulin-responsive dGlc transport. These data are consistent with a
      role of IRS-1 in insulin signaling to the glucose transport system.

PMID- 7507667
TI  - Eclosion hormone-mediated signal transduction in the silkworm abdominal ganglia:
      involvement of a cascade from inositol(1,4,5)trisphosphate to cyclic GMP.
AB  - The neuropeptide eclosion hormone triggers ecdysis behavior in lepidopteran
      insects. We have previously shown that the eclosion hormone stimulates the
      formation of two intracellular second messengers, cGMP and
      inositol(1,4,5)trisphosphate in the abdominal ganglia of Bombyx mori. In order to
      elucidate the intracellular signaling pathway involving these second messengers,
      we studied the eclosion hormone-mediated signal transduction using saponin
      treated abdominal ganglia. We obtained the following results; i) eclosion hormone
      activated nitric oxide synthase, ii) the eclosion hormone-induced cGMP increase
      was inhibited by various enzyme inhibitors such as NG-nitro-arginine; a nitric
      oxide synthase inhibitor, EGTA; a calcium chelating reagent, W-5; a calmodulin
      inhibitor and compound 48/80; a phospholipase C inhibitor and iii) the
      inositol(1,4,5)-trisphosphate stimulated the formation of cGMP, in the Bombyx
      abdominal ganglia. Based on these findings we tentatively propose a hypothetical
      pathway: The signal initially triggered by eclosion hormone and eclosion hormone
      receptor complex induces activation of phospholipase C which produces
      inositol(1,4,5)trisphosphate. Inositol(1,4,5)trisphosphate increases
      intracellular Ca2+, followed by subsequent activation of nitric oxide synthase
      through the formation of Ca(2+)-calmodulin complex. The reaction product, nitric
      oxide acts on soluble guanylate cyclase to stimulate cGMP formation which induces
      the ecdysis behavior in Bombyx pharate adults.

PMID- 7507668
TI  - A variant mRNA species encoding a truncated form of Fas antigen in the rat liver.
AB  - A variant form of the Fas antigen cDNA was isolated from the rat liver. The cDNA
      contains an insertion sequence of 25 nucleotide residues and codes for a protein
      consisting of 65 amino acids representing a signal peptide and an N-terminal
      portion of the extracytoplasmic domain of Fas antigen. The expression of a
      variant mRNA species is less abundant in the liver compared with that of an
      ordinary mRNA species. The variant mRNA, though its function is unknown, is
      plausibly produced by an alternative splicing.

PMID- 7507669
TI  - Receptors specific for Amadori-modified glycated albumin on murine endothelial
      cells.
AB  - Albumin modified by Amadori glucose adducts has been shown to modulate
      endothelial and glomerular mesangial cell biology. Recognizing that circulating
      proteins may trigger cellular events through ligand binding, we examined murine
      aortic endothelial cells for the expression of a receptor system that recognizes
      fructosyllysine epitopes in glycated albumin. Endothelial cells contain membrane
      associated polypeptides that bind Amadori-modified glycated albumin and exhibit
      traditional receptor characteristics of dose-responsivity, saturability and
      ligand specificity. Nonglycated albumin does not compete for binding to the
      receptor, and the interaction of glycated albumin with its receptor is blocked by
      a monoclonal antibody that selectively reacts with the Amadori adduct in glycated
      albumin. The findings suggest that a ligand-receptor system specific to Amadori
      glucose adducts mediates the biologic effects of glycated albumin.

PMID- 7507670
TI  - Parathyroid hormone-related protein is produced by cultured endothelial cells: a
      possible role in angiogenesis.
AB  - Parathyroid hormone-related protein (PTHrP) is produced by various normal and
      neoplastic tissues. Even if the physiological function(s) of PTHrP is unclear,
      evidence suggests that the protein may participate in the local regulation of
      smooth muscle contractility. We show here that PTHrP is produced in endothelial
      cells cultured from human umbilical veins as demonstrated both at the mRNA and
      protein level. The expression of PTHrP can be upregulated by the phorbol ester 12
      O-tetradecanoyl-phorbol-13-acetate, which is known to stimulate endothelial cell
      differentiation and angiogenesis in vitro. Unlike smooth muscle cells, the
      endothelial cells do not express the parathyroid hormone (PTH)/PTHrP receptor
      mRNA, nor could specific binding of the protein be detected. We therefore suggest
      that PTHrP produced by endothelial cells acts on smooth muscle cells and may be
      of importance for the growth and development of new vasculature.

PMID- 7507671
TI  - Expression of the large myelin-associated glycoprotein isoform in rat
      oligodendrocytes around cerebral infarcts.
AB  - An immunohistochemical method that uses two specific antisera-distinguishable
      myelin-associated glycoprotein (MAG) isoforms showed an expression of large MAG
      isoform (L-MAG) protein in the oligodendrocyte cytoplasms in the white matter
      around experimental cerebral infarcts produced by occlusion of the left middle
      cerebral artery in the rat. L-MAG protein also was detected in the white matter
      on the contralateral side. This protein appears prior to S-MAG protein in
      myelination and remyelination in the central and peripheral nervous systems, and
      is believed to function in myelin formation. Because L-MAG protein has been found
      in the oligodendrocyte cytoplasm only in the early development period, its
      appearance in this cytoplasm after ischemic insult is evidence of MAG
      regeneration.

PMID- 7507672
TI  - Differences between thymic and splenic cells of the rat: biochemical and physico
      chemical investigations in vitro on DNA topoisomerase II--inhibitors and thiyl
      radicals.
AB  - Interactions of novobiocin (NB) and nalidixic acid (NA) with thiols were
      investigated in vitro in thymic (T-) and splenic (S-) cells of the rat, by
      determining nucleic acid synthesis as well as nucleoid sedimentation and
      viscosity of alkaline cell lysates. In T-cells NB, at concentrations of 0.35-1.4
      mM, increased unscheduled DNA synthesis (UDS) and RNA synthesis (RNS), whereas S
      cells underwent a dose-dependent inhibition of UDS and RNS following exposure to
      NB at concentrations > 0.7 mM. Combining NA and thiols (e.g., dithiothreitol)
      resulted in a slight stimulation of UDS in S-cells and in a highly significant
      increase of UDS in T-cells ascribed to a depletion of the cellular thymidine
      pool. In both cell types, neither NB nor NA exerted a significant effect on thiol
      induced DNA damage. At a concentration of 1.4 mM, NB increased the viscosity of
      alkaline T-cell lysates; the opposite effect was observed in S-cells. From these
      results as well as from previous investigations we conclude that T- and S-cells
      differ in their state of chromatin conformation. This interpretation offers a
      simple model for the study of the influence of chromatin structure on cell
      specific physico-and/or chemico-biological interactions.

PMID- 7507673
TI  - Chromatin texture features in hematoxylin and eosin-stained prostate tissue.
AB  - A pilot study was undertaken to determine the expression of certain nuclear
      features in prostatic lesions. Twenty cases, 5 of hyperplasia and 5 each of
      carcinoma, Mostofi grades I-III, were selected as a training set, and an
      additional 20 cases were used as a test set, including 5 cases of hyperplasia and
      5 cases each in Mostofi grades I-III. Images of hematoxylin and eosin-stained, 4
      microns paraffin sections were obtained with a JVC BY-110 three-color camera and
      digitized by an IBM personal computer with a Matrox MVP-AT/NP imaging board.
      Thirty nuclei for each case from the training set, for a total of 600 nuclei, and
      10 nuclei for each case from the test set, for a total of 200 nuclei, were
      analyzed by quantitative cytometric software on a SUN 3/60 workstation. A linear
      discriminant model was used for statistical analysis. One hundred percent of the
      hyperplasia group, 98% of the low grade group, 92% of the medium grade group and
      82% of the high grade group were classified correctly in the test set with an
      overall success rate of 93%. Statistically significant chromatin texture features
      included heterogeneity, condensation, margination, run length nonuniformity, long
      run emphasis, gray level nonuniformity and inertia. Area, roundness and staining
      intensity (total extinction) were also significant. The results with standard
      hematoxylin and eosin-stained tissue sections were similar to those previously
      obtained with Feulgen-stained material. These results indicate that routine
      hematoxylin and eosin-stained material offers consistent diagnostic clues.

PMID- 7507674
TI  - Biocompatibility of visible light-polymerized denture base resins.
AB  - The biocompatibility of three commercial formulations of visible light
      polymerized denture base resins was studied to determine its effects on the RNA
      and DNA synthesis of oral epithelial cells in vitro. Isotope incorporation into
      RNA or DNA was measured after 24 hours of incubation with isotope and 48 hours of
      exposure to resin. The resins were shown to significantly inhibit the synthesis
      of both nucleotides as compared to a heat-processed resin control. Increasing the
      polymerization time can mitigate the toxicity of some of the resins. The air
      barrier coatings used to prevent oxygen inhibition of polymerization increased
      the toxic effects of two resins and decreased that of one of the materials. These
      investigations suggest that visible light-polymerized denture resins may impair
      the replication of oral epithelial cells. DNA synthesis is more sensitive to the
      toxic effects of the materials, which may relate to the ability to cause mucosal
      pathology. The cytotoxic effects may relate to the presence of unpolymerized
      resin constituents or polymerization by-products.

PMID- 7507675
TI  - FK506 conversion for intractable rejection of the liver allograft.
AB  - Twenty-seven liver transplant recipients with intractable, biopsy-proven, acute
      or chronic rejection (defined as vanishing bile duct syndrome) were converted
      from cyclosporin to FK506. Successful conversion was achieved in 9 of 15 patients
      with acute rejection and in 6 of 12 patients with vanishing bile duct syndrome. A
      normal bilirubin was achieved more quickly in those with acute rejection (within
      1 month) than in those with chronic rejection (within 3 months). A preconversion
      total bilirubin of less than 12 mg/dl was considered significant with regard to a
      successful outcome (P = 0.002). Graft survival was 66.7% and patient survival 73%
      in the case of acute rejection, and 50% and 66.7%, respectively, in the case of
      chronic rejection. Nephrotoxicity, neurotoxicity, and gastrointestinal side
      effects were the most serious complications of FK506 conversion. Six of ten
      patients had a drop in GFR that was 50% or greater after a minimum of 1 month of
      FK506 exposure. The mean maintenance dose of FK506 to maintain FK506 serum levels
      of 0.5-1.5 ng/ml was 0.07 mg/kg per 12 h for adults (half the recommended dose),
      compared to 0.15 mg/kg per 12 h for pediatric patients. This study demonstrates
      that FK506 can be used successfully to convert patients with intractable acute
      and chronic rejection. Careful adjustments of FK506 dosages and levels are
      required to minimize side effects.

PMID- 7507676
TI  - Living related liver transplantation across ABO blood groups with FK506 and OKT3.
AB  - In living related liver transplantation (LRLT), the use of graft livers across
      ABO blood groups is unavoidable since the organ donor is usually one of the
      recipient's parents. This report presents our initial experiences with LRLT,
      focusing on ABO-incompatible cases. From June 1990 to May 1992, we successfully
      performed a series of 34 LRLT on children (15 males and 19 females) ranging in
      age from 7 months to 15 years. Overall recipient survival rates were 90% (25/28)
      in elective LRLT and 50% (3/6) in emergency LRLT. These cases were classified
      into three groups: ABO blood group-identical (n = 21), compatible (n = 10), and
      incompatible (n = 3). The immunosuppressive regimen consisted of FK506 and low
      dose steroids in the first two groups. In the incompatible cases, exchange
      transfusion was performed to decrease anti-A and/or -B antibody titers before
      LRLT, and prophylactic OKT3 was added to FK506 and steroids after LRLT. No
      significant difference in recipient and graft survival was observed among the
      groups. In the identical group, no rejection episodes have been observed thus
      far. Rejection occurred in two out of the ten compatible cases. Among the
      incompatible cases, one recipient had mild rejection and was treated. The
      remaining two recipients have had no rejection episodes thus far. Although all
      three recipients had cytomegalovirus (CMV) infection, they were successfully
      treated with ganciclovir, and no lethal infection has developed in any of these
      cases. The present results suggest that graft livers from living related donors
      across ABO blood groups can function well with FK506, low-dose steroids, and
      prophylactic OKT3 without causing lethal complications.

PMID- 7507677
TI  - Conversion from cyclosporin to FK 506 after liver transplantation.
AB  - Thirty-seven liver-grafted patients with steroid-resistant acute or chronic graft
      rejection or with cyclosporin-related complications were converted from CyA to FK
      506. The clinical outcome of the patients primarily depended on the degree of
      liver dysfunction present at initiation of FK 506 treatment. In patients switched
      to FK 506 for treatment of acute or early chronic graft rejection, CyA
      nephrotoxicity, or CyA malabsorption, the FK 506 therapy was associated with a
      clear improvement in the clinical course. In contrast, in patients with advanced
      chronic graft rejection, a lower response rate to the conversion in
      immunosuppression was observed. The lower response rate was associated with a
      higher patient mortality. These studies demonstrate that FK 506 represents a
      valuable alternative immunosuppressant for liver-grafted patients. The conversion
      from CyA to FK 506 should take place before serious--and potentially irreversible
      -disturbances in liver function are observed.

PMID- 7507678
TI  - Binding and specificity of major immunoglobulin classes of preformed human anti
      pig heart antibodies.
AB  - Preformed human anti-pig antibodies isolated from perfused pig hearts were used
      to analyze the binding of various immunoglobulin classes to cultured pig kidney
      cells. All anti-pig immunoglobulins (i.e., IgG, IgA, and IgM) were localized on
      the cell surface by the use of an indirect immunofluorescence technique. Anti-pig
      immunoglobulins also competed for the pig cell surface epitopes with Griffonia
      simplicifolia lectin (GS-I-B4), which is specific for alpha-galactosyl residues.
      This study provides further evidence that preformed human antibodies recognizing
      alpha-galactosyl-containing epitopes (anti-gal antibodies) could be an important
      factor in hyperacute rejection of pig organs.

PMID- 7507679
TI  - Detection of gastrin mRNA in fresh human colonic carcinomas by reverse
      transcription-polymerase chain reaction.
AB  - To investigate the hypothesis that gastrin might be synthesized by tumour tissues
      in cancer of the colon, samples from six human colon tumours, one hepatic
      metastasis, four normal colonic mucosal samples and two antral and one fundic
      gastric mucosal samples from nine patients were analysed to determine whether
      gastrin mRNA was present. RNA was extracted from surgical specimens by
      ultracentrifugation on a CsCl cushion, purified using the guanidinium thiocyanate
      method, reverse-transcribed and amplified by polymerase chain reaction. Gastrin
      mRNA was detected in each colonic carcinoma sample (including the hepatic
      metastasis), while no such signal was observed in normal colon biopsies. Positive
      and negative controls (gastric antrum and fundus respectively) gave the expected
      results. In each of the positive samples, the chemiluminescent revelation of
      amplified products after Southern blotting corresponded to gastrin mRNA without
      the intron. These findings demonstrate the ability of primary and metastatic
      human colonic tumours to produce gastrin mRNA. Since malignant cell lines have
      been reported to produce gastrin peptide, and since gastrin receptors were
      present in some cases, our results support the idea that gastrin may be involved
      in an autocrine mechanism.

PMID- 7507680
TI  - A monoclonal antibody to a conserved sequence in the extracellular domain
      recognizes the angiotensin II AT1 receptor in mammalian target tissues.
AB  - We have generated hybridomas which secrete monoclonal antibodies to the AT1
      subtype of the angiotensin II receptor (AT1 receptor). These were obtained after
      immunization of Balb C/c mice with synthetic peptides representing sequences from
      either the extracellular domain (residues 8-17) or the intracellular domain
      (residues 229-237) of the AT1 receptor. Hybridoma populations were first screened
      for the production of antibodies which bound to rat liver cells. Further
      selection, and cloning by limiting dilution, was carried out for antibodies which
      bound specifically to rat adrenal glomerulosa cells. Confirmation that the
      antibody designated 6313/G2 interacted with the angiotensin II receptor was
      obtained using COS-7 cells transfected with AT1A receptor cDNA. In particular,
      the initial characterization of 6313/G2 showed specific immunofluorescence of
      vascular endothelium.

PMID- 7507681
TI  - In situ expression of cytokines and cellular adhesion molecules in the skin of
      patients with systemic sclerosis. Their role in early and late disease.
AB  - Cytokines and cellular adhesion molecules (CAMs) may play a role in the
      inflammatory and fibrotic processes underlying systemic sclerosis (SSc). We
      compared the immunohistological distribution of cytokines and CAMs in skin
      biopsies from 12 SSc patients and 14 normal (NL) individuals. Among CAMs,
      vascular cell adhesion molecule-1 (VCAM-1), which mediates leukocyte-endothelial
      adhesion, showed increased expression on SSc versus NL endothelium and stratum
      granulosum. P-selectin was up-regulated in SSc versus NL stratum granulosum. The
      CD44 lymphocyte homing receptor showed the most striking differences between SSc
      and NL: its expression was increased in SSc stratum granulosum, stratum spinosum,
      on lymphocytes, and macrophages. Regarding cytokines, interleukin-6 (IL-6)
      expression was increased on SSc versus NL endothelium and fibroblasts. Tumor
      necrosis factor-alpha (TNF-alpha) reactivity was more prevalent in SSc than NL
      stratum granulosum, whereas IL-8 expression was higher on SSc compared to NL
      endothelium. Some CAMs, such as VCAM-1 and P-selectin, and cytokines, namely TNF
      alpha and IL-8, were more commonly found in skin biopsies taken from early (< or
      = 1 year's duration) SSc, while others, such as IL-6, showed up-regulation in the
      late stage of the disease. The results suggest that certain CAMs and cytokines
      may play a differential role in both the early, inflammatory, and the late,
      fibrotic stage of SSc.

PMID- 7507683
TI  - Molecular basis of the exclusive low-temperature synthesis of an enzyme in E.
      coli: penicillin acylase.
AB  - The enzyme penicillin acylase is synthesized by Escherichia coli only at growth
      temperatures below 30 degrees C. The biochemical basis of this strict temperature
      dependent formation of an enzyme was investigated. When the gene (pac) was under
      the control of the lacUV5 promoter it showed the same temperature-dependent
      expression as the chromosomally encoded gene transcribed from its own promoter.
      This indicates that translation of the pac mRNA rather than transcription of the
      gene is temperature-dependent. This conclusion could be further confirmed by
      Northern hybridisation and by analysis of pac-lacZ transcriptional fusions.
      TnphoA insertion mutagenesis and experiments in which the promoter and 5'
      sequence encoding the signal peptide of the pac gene was exchanged with those of
      the cyclodextrin glycosyltransferase gene from Klebsiella oxytoca localised the
      region of pac mRNA responsible for the temperature-sensitive translation to the
      5'-untranslated region and/or the signal peptide. Extension of the 5 nucleotide
      long spacer separating the Shine-Dalgarno motif from the AUG initiation codon by
      one or three nucleotides lead to partial or full synthesis of penicillin acylase
      precursor at 40 degrees C, respectively. The precursor of penicillin acylase
      formed at 40 degrees C by the mutant variants or when placed under the control of
      a heterologous upstream region was associated with the membrane but could not be
      translocated. Taken together these data suggest that transport and translation of
      the penicillin acylase precursor are coupled and that the short Shine-Dalgarno
      AUG distance interferes with a competent interaction between the translation
      initiation complex and the export system at high temperature. Moreover, evidence
      was also provided which indicates a direct effect of temperature on the
      conformation of the precursor and it is proposed that the lack of translation at
      high temperatures has been selected to prevent the accumulation of transport
      incompetent protein locked in the membrane.

PMID- 7507682
TI  - Hematopoietic origin of human natural killer (NK) cells: generation from immature
      progenitors.
AB  - Human natural killer (NK) cells originate from bone marrow, but little is known
      about NK cell progenitors and ontogeny. We studied the phenotype and functional
      activity of NK cells derived from highly purified human bone marrow CD34+ cells,
      which exhibited neither lytic activity nor expression of surface antigens
      characteristic of NK (CD56) or T (CD3) cells. However, when cultured with
      hematopoietic growth factors or feeder layers for up to 4 weeks, up to 86%
      functional CD56+ cells were seen in the absence of mature T cell development.
      CD56+ cells appeared in all cultures at 2 or 3 weeks, with the largest percentage
      in those exposed to IL-2. These studies demonstrated that NK cells arise 'in
      vitro' from immature bone marrow progenitors and also suggest a separate origin
      and differentiation pathway for NK and T cells.

PMID- 7507684
TI  - Role of CD40-CD40-ligand interaction in Ig-isotype switching.
AB  - Ig-isotype switching to IgE requires interleukin-4 and a contact-dependent T-cell
      signal delivered by the ligand for CD40. The recent discovery that defects in the
      gene encoding the CD40 ligand are the underlying cause of the X-linked hyper IgM
      syndrome highlights the role of CD40 and its ligand in Ig-isotype switching.

PMID- 7507686
TI  - Translational effects.

PMID- 7507685
TI  - Modern concepts of immunotherapy.
AB  - Although common allergies have been considered as immediate IgE antibody mediated
      responses, attention is now turning to inflammatory responses that appear to be
      initiated by T-cell responses to peptides from allergens presented in combination
      with HLA class II molecules. Although classic immunotherapy with allergen
      extracts has been found to downregulate these T-cell responses, more efficient
      and safe methods are being sought.

PMID- 7507687
TI  - Carboplatin in advanced hormone refractory prostatic cancer patients.
AB  - 25 patients with measurable or evaluable metastatic prostate cancer, progressive
      after hormonal treatment, were treated weekly with carboplatin 150 mg/m2
      intravenously. The weekly schedule allowed higher dose intensity carboplatin
      administration with respect to the common monthly cycles. Toxicity was manageable
      even in elderly patients with extensive bone metastases and consisted primarily
      of myelosuppression. 4 out of 24 evaluable patients (17%) had a partial response
      and 12 (50%) had disease stabilisation. The median response duration was 7
      months. Prostate-specific antigen and prostatic acid phosphatase serial values
      showed a correlation with disease response in only 47 and 50% of patients,
      respectively. These results suggest that carboplatin possesses a moderate but
      definite activity in prostate cancer patients.

PMID- 7507688
TI  - The effect of endocrine therapy on fibroblast growth factor-like activity in
      nitrosomethylurea-induced rat mammary tumours.
AB  - Tumour regression following ovariectomy of rats bearing nitrosomethylurea-induced
      mammary tumours has been well characterised as a model for oestrogen receptor
      (ER)-positive breast cancer. We have shown that a similar regression response can
      be induced in these rats by the cytotoxic drug doxorubicin. Conditioned medium
      (CM) from serum-free explant cultures of the mammary tumours of ovariectomised
      rats showed a striking increase in its ability to transform NR6 cells compared to
      that of control or doxorubicin-treated rats (P = 0.001, t-test). Activity was
      also present in CM derived from rat uteri but not in ER-negative tissues such as
      skin and liver. Activity was further defined as fibroblast growth factor (FGF)
      like by its strong affinity to heparin, partial neutralisation by antibodies to
      acidic FGF (aFGF) and partial co-elution with aFGF on salt elution from heparin.
      Both aFGF protein and mRNA were detected in tissue preparations of rat tumours
      and uterus.

PMID- 7507689
TI  - [Cytokines and nervous system].

PMID- 7507690
TI  - [GH-secreting pituitary adenomas--correlation between clinical features, growth
      potential and histopathological studies].
AB  - We compared clinical features, including endocrinological and radiological
      findings, histological features and the proliferative parameters (PCNA, MIB-1 and
      AgNORs) with immunohistochemical features in growth hormone (GH) secreting
      pituitary adenomas. 18 cases were divided into two groups based on
      immunohistochemical intracytoplasmic stainings for cytokeratin: a prominent dot
      like pattern (group I, 6 cases) and a diffuse perinuclear pattern (group II, 12
      cases). Patients in group I (6 females, m = 37.6 years old) were younger, showed
      female predominance and had a shorter history of acromegaly compared with
      patients in group II (7 males, 5 females, m = 44.9 years old). Although the size
      of the adenomas tend to be larger in group I, no difference was recognized in
      plasma GH levels between the two groups. Increased serum prolactin (PRL) levels
      were accompanied more common in group I. Abnormal GH responses to TRH and LHRH
      injection and GH suppressions to bromocriptine administration were more
      frequently noted in group II than group I. Surgical approaches were transcranial
      in most cases of group I and transphenoidal in group II. There was no difference
      in surgical results as to the correction rate of GH levels between the two
      groups. Histopathologically, group I adenomas were mostly chromophobic, weakly
      positive for GH, and were generally negative for PRL and alpha-subunit. On the
      other hand, group II adenomas were mostly acidophilic, diffusely stained for GH,
      and were often positive for PRL and alpha-subunit. However, there was no
      significant difference in proliferating parameters between the two
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507692
TI  - Localisation of monoclonal antibodies reacting with different epitopes on
      carcinoembryonic antigen (CEA)--implications for targeted therapy.
AB  - Antibody targeting has potential for selective delivery of cancer therapy.
      However, there is a wide variation in the degree of antibody localisation in
      individual patients with colorectal adenocarcinoma. Colorectal adenocarcinomas
      are composed of glandular structures separated from fibrovascular stroma by a
      basal lamina which may represent a significant barrier to extravasated antibody.
      Basement membrane-associated CEA epitopes may be more accessible to antibodies
      than those which are cytoplasmic or lumenal. We have investigated by
      immunohistochemistry and in vivo localisation, the extent to which distribution
      of antigen epitopes influences targeting. Two monoclonal antibodies (A5B7 and
      EA77) recognising non-overlapping CEA epitopes were reacted immunohistochemically
      with samples of 39 tumours. Intensity and site of reaction were assessed for
      basement membrane, cytoplasmic or lumenal surface association. 125I-labelled
      antibodies were injected into nude mice bearing LS174T tumour. Per cent injected
      activity per gram was measured in tumour and normal tissues, 24, 72 and 168 h
      later. Tissues reacted immunohistochemically for CEA were autoradiographed to
      assess the relationship of injected antibody to target antigen.
      Immunohistochemistry showed that A5B7 antibody favours basement membrane aspects
      of malignant glands; in contrast, EA77 concentrated generally on lumenal
      surfaces. In vivo localisation showed that per cent inj.act g-1 in tumour for
      A5B7 reached 36.5% at 24 h. EA77 localised to a lesser extent (9.1% at 24 h),
      despite a longer circulatory half-life. Autoradiography combined with
      immunohistochemistry showed A5B7 reacting with antigen close to vasculature after
      24 h, slowly penetrating deeper parts of the tumour by 72 h. In contrast, EA77
      was confined mainly to fibrovascular stroma, showing little labelling of antigen
      positive tumour cells. Localisation differences between A5B7 and EA77 may partly
      be due to accessibility of epitopes on tumour cells.

PMID- 7507691
TI  - Effectiveness of HB2 (anti-CD7)--saporin immunotoxin in an in vivo model of human
      T-cell leukaemia developed in severe combined immunodeficient mice.
AB  - The transplantation of the human T-cell acute lymphoblastic leukaemia (T-ALL)
      cell line HSB-2 into severe combined immunodeficient (SCID) mice was found to
      produce a disseminated pattern of leukaemia similar to that seen in man. The
      intravenous injection of 10(7) HSB-2 cells was associated with a universally
      fatal leukaemia. Histopathological examination of animals revealed the spread of
      leukaemia initially from bone marrow to involve all major organs including the
      meninges. An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7
      MAb HB2 to the ribosome-inactivating protein saporin. An in vitro protein
      synthesis inhibition assay revealed specific delivery of HB2-Sap immunotoxin (IT)
      to CD7+ HSB-2 target cells with an IC50 of 4.5 pM. When SCID mice were injected
      with 10(6) HSB-2 cells and then treated 8 days later with a single intravenous
      dose of 10 micrograms of immunotoxin there was a significant therapeutic effect
      evidenced by the numbers of animals surviving in the therapy group compared with
      untreated controls (chi 2 = 5.348, P = 0.021). These results demonstrate the
      useful application of human leukaemia xenografts in SCID mice and the potential
      therapeutic effect of an anti-CD7 immunotoxin in human T-ALL.

PMID- 7507693
TI  - Male fertility after VAPEC-B chemotherapy for Hodgkin's disease and non-Hodgkin's
      lymphoma.
AB  - Semen analysis was performed in 14 men a median of 13.5 months after completion
      of VAPEC-B chemotherapy for Hodgkin's disease or non-Hodgkin's lymphoma. Semen
      from 12 patients contained motile spermatozoa, and in nine cases the count was >
      20 million ml-1. One patient was azoospermic (VAPEC-B followed by pelvic
      radiotherapy) and another had a count of 21 million ml-1 but sperm were non
      motile. These findings suggest that, in the majority of cases, VAPEC-B
      chemotherapy does not cause permanent damage to the male germinal epithelium. A
      more detailed study of gonadal function in males and females before and after
      treatment with VAPEC-B for Hodgkin's disease is currently in progress.

PMID- 7507694
TI  - Cytogenetic findings in malignant triton tumor.
AB  - Malignant triton tumor is a rare histologic variant of malignant schwannoma that
      shows both neural and skeletal muscle differentiation. In this study, cytogenetic
      analysis of a recurrent malignant triton tumor of the forearm from a 26-year-old
      female and a primary paraspinal malignant triton tumor from a 27-year-old female
      revealed complex karyotypes displaying multiple numerical and structural
      abnormalities. Abnormalities shared by both tumors included three copies of
      chromosome 22 and structural rearrangements of chromosomes 2, 7, and 21 at
      identical or closely located breakpoints.

PMID- 7507695
TI  - Cytogenetic and molecular analysis of 6q deletions in Burkitt's lymphoma cell
      lines.
AB  - Although abnormalities of chromosome 6 have frequently been observed in Burkitt's
      lymphoma (BL), they have so far not been defined by modern cytogenetic and
      molecular methods. By a combination of high-resolution chromosome banding,
      fluorescence in situ hybridization (FISH), and loss of heterozygosity (LOH)
      analysis, we have examined the nature of aberrations affecting chromosome 6 in 7
      previously established BL cell lines. All cell lines exhibited the characteristic
      translocations associated with BL; 5 had t(8;14)(q24;q32) and 2 had
      t(8;22)(q24;q11). Three cell lines had deletions of 6q; 3 others had
      rearrangements affecting 6q, whereas one cell line had apparently normal
      chromosomes 6. FISH analysis of the three deletions established that they were
      interstitial. LOH analysis with probes mapped to the 6q26-27 region confirmed the
      sub-telomeric interstitial deletion in cell line BL-108, which had a
      del(6)(q23q27). All informative loci mapped to 6q26-27 (5/7) were deleted in BL
      74, which had no apparent cytogenetic abnormality in chromosome 6, thus
      documenting a sub-microscopic deletion. These data define the cytogenetic and
      molecular limits of 6q deletions in BL and are consistent with our previous
      demonstration of LOH analysis of the site of a candidate tumor suppressor gene in
      the 6q25-27 region.

PMID- 7507696
TI  - Trisomy 7: a potential cytogenetic marker of human prostate cancer progression.
AB  - We used the fluorescence in situ hybridization (FISH) method to show that
      chromosome 7 trisomy is associated with the progression of human prostate cancer.
      Thirty-six specimens including 15 primary prostate carcinomas, 16 metastatic
      lesions, and 5 normal prostate tissues, as well as 2 prostate carcinoma cell
      lines of different tumorigenic potential, were examined for chromosome 7
      aneuploidy. Our results showed that the androgen-unresponsive tumorigenic cell
      line PC-3 exhibited a significantly higher ratio of chromosome 7 to total
      chromosome number than the androgen-responsive nontumorigenic cell line LNCaP (P
      = 0.001). In prostate specimens, the frequency of trisomy 7 cells was
      significantly increased (P < 0.05) in the advanced stage tumors (C and DI) but
      not in the early (B) stage tumors or normal prostatic tissue. Furthermore,
      metastases showed a higher frequency of trisomy 7 cells than primary tumors (P =
      0.005). In 2 patients with paired primary and metastatic tumors, trisomy 7 cells
      increased from 4-7% in the primary tumors to 42-45% in the metastatic tumor cells
      in the bone marrow. Therefore, our data suggest that trisomy 7 may be a common
      feature associated with local and metastatic progression and serve as a novel
      marker for human prostate cancer progression.

PMID- 7507697
TI  - Integration site of human papillomavirus type-18 DNA in chromosome band 8q22.1 of
      C4-I cervical carcinoma: DNase I hypersensitivity and methylation of cellular
      flanking sequences.
AB  - The C4-I cell line derived from a non-keratinizing squamous cell carcinoma of the
      uterine cervix contains integrated human papillomavirus-18 DNA. Fluorescence in
      situ hybridization of C4-I cells demonstrated a single viral integration site at
      8q22.1 on a derivative chromosome originating from an 8q;12q translocation. 8q22
      is a site of chromosome fragility and is also recombinogenic in several human
      malignancies. DNase I hypersensitivity of the integration site was studied with a
      cellular flanking probe. A hypersensitive site was detected within 3 kb from
      viral DNA. The integration sites are undermethylated in C4-I and HeLa cells and
      fully methylated in tumor cell lines of other origin, such as lymphoid cells.

PMID- 7507698
TI  - Molecular and cytogenetic analysis of chromosome 9 deletions in 75 malignant
      gliomas.
AB  - A deletion mapping analysis of chromosome 9 has been performed on a series of 75
      samples derived from malignant gliomas. A total of 27 tumors displayed different
      deletions for the loci studied (D9S1, NRASLI, D9S18, IFNA, and IFNBI). In most
      instances, losses involving the markers located on the short arm of chromosome 9
      were observed, and only two samples were characterized by losses of the short and
      long arms. Either partial or complete homozygous deletions of IFN genes were
      observed in 15 cases, and 12 other samples showed hemizygous deletions for these
      genes. The results show that the 9p abnormalities are not exclusive to high-grade
      astrocytic tumors, as some low-grade samples (two astrocytoma grade II and six
      oligodendrogliomas) displayed this anomaly which, in a few instances, was the
      sole abnormality detected.

PMID- 7507699
TI  - Patterns of DNA amplification at band q13 of chromosome 11 in human breast
      cancer.
AB  - In an attempt to verify the nature of amplification events at band q13 on
      chromosome 11 we surveyed the amplification status of ten molecular markers
      specific for this region (GSTP, SEA, D11S97, D11S146, BCLI, PRADI/CCNDI,
      HST/FGF4, INT2/FGF3, EMSI, and DIIS833E) in a panel of 389 primary breast
      carcinoma DNA samples. Eighty-eight tumors (23%) showed at least one of these
      markers amplified, but in a majority of the cases amplification encompassed more
      than one of the tested loci. Our data confirm that amplicons at 11q13 can cover
      large portions of DNA and are consistent with the existence of several cores of
      amplification. One important core seems to be, as previously described, centered
      around PRADI/CCNDI; 57 tumors (14.7%) showed amplification at PRADI/CCNDI either
      alone (one tumor) or along with amplification of BCLI or INT2/FGF3. The level of
      amplification of PRADI/CCNDI sometimes exceeded that of surrounding markers.
      Three additional amplification events occurring independently of amplification of
      PRADI/CCNDI were also detected. Centromeric to BCLI, probes to DIIS97, and
      DIIS146 detected amplification in 60 tumors (15.4%) and were often the only
      amplified markers. Telomeric to INT2/FGF3, DIIS833E was found amplified alone in
      ten tumors, and it was the most amplified marker in another six cases. At a
      shorter distance of INT2/FGF3, EMSI was the only amplified marker in two tumors,
      with a level of amplification that could exceed that of PRADI/CCNDI and DIIS833E.
      Our data thus suggest the existence of four independent amplified regions within
      band 11q13 in breast cancer.

PMID- 7507700
TI  - RARA and PML gene rearrangements in acute promyelocytic leukemia with complex
      translocations and atypical features.
AB  - The translocation t(15;17) associated with acute promyelocytic leukemia (APL)
      results in fusion of the retinoic acid receptor alpha (RARA) gene on chromosome
      17 with the putative transcription factor gene, PML, on chromosome 15. We report
      three cases of APL with complex cytogenetic translocations and five cases with
      atypical phenotypic features with rearrangements within or adjacent to the second
      intron of the RARA gene. Two patients demonstrated three-way translocations
      involving chromosomes 3, 15, and 17, but with differing breakpoints on the short
      arm of chromosome 3. A third patient developed a complex karyotype at the time of
      third relapse, but with no change in RARA and PML gene rearrangement pattern.
      Three patients had normal karyotypes; however, only small numbers of cells could
      be analyzed. One patient's leukemic cells expressed the T-cell-associated antigen
      CD2 and revealed T-cell receptor beta and gamma gene rearrangements. The
      localization of breakpoints to the second intron of the RARA gene in
      cytogenetically and phenotypically atypical cases provides additional support for
      a requisite role of the PML/RARA fusion gene in the pathogenesis of APL.

PMID- 7507701
TI  - Mapping of the 8q23 translocation breakpoint of t(8;13) observed in a patient
      with multiple exostoses.
AB  - A detailed cytogenetic map was constructed around the chromosomal breakpoint of
      t(8;13) observed in a patient with multiple exostoses. The order of seven loci
      defined by cosmid clones mapped to 8q23 was determined by means of two-color
      fluorescence in situ hybridization (FISH) on elongated prophase chromosomes, and
      localizations of these markers relative to the breakpoint were examined. The
      results indicated that loci defined by cC18-553 and cC18-1512 flank the
      breakpoint. By pulsed-field gel electrophoresis of DNA digested with BssHII and
      Southern hybridization with cC18-1512, DNA from the patient showed a band which
      was not observed in DNA isolated from either parent. As the normal size of this
      BssHII fragment is 600 kb, the chromosomal breakpoint probably lies less than 600
      kb away from cC18-1512.

PMID- 7507702
TI  - Localization of amplified MYC gene sequences to double minute chromosomes in
      acute myelogenous leukemia.
AB  - Cytogenetic and molecular studies were performed on two dmin-bearing acute
      myelogenous leukemia (FAB-M2) samples. Both cases were characterized by complex
      karyotypes containing interstitial deletions of the long arm of chromosome 8
      altering band 8q24.1, aberrations affecting the short arm of chromosome 17, and
      multiple double minute chromosomes (dmin). Using a 1.4 kb cDNA probe coding for
      the third exon of the MYC oncogene, DNA slot blots indicated MYC gene sequences
      were amplified in both samples. Fluorescence in situ hybridization using a 9.0 kb
      genomic probe for MYC was performed in one case and localized the amplified MYC
      gene sequences to the dmin. Neither patient achieved a complete remission using
      traditional induction chemotherapy. The complex karyology with amplification of
      MYC gene sequences appears to represent a poor prognostic subgroup of acute
      myelogenous leukemia.

PMID- 7507703
TI  - Cardiac myxoma characterized by clonal telomeric association.
AB  - We report on the cytogenetic analysis of a case of cardiac myxoma of the
      "syndrome myxoma" type, in which clonal telomeric associations between
      chromosomes 13 and 15, as well as nonclonal telomeric associations between
      chromosomes 12 and 17 and between chromosome 2 and an unidentified chromosome
      were observed. Nonclonal structural abnormalities were also present. This is the
      second reported case of cytogenetic abnormalities of syndrome cardiac myxoma, and
      the fourth case in which telomeric associations have been described.

PMID- 7507704
TI  - Multiple genetic events involving RB1 gene deletion and amplification of
      chromosome 21 in a case of acute lymphocytic leukemia.
AB  - A patient with acute lymphocytic leukemia was found to have a hyperdiploid
      karyotype, characterized by hexasomy 21 and del(7)(p15). It was shown that the
      four extra copies of chromosome 21 were all derived from only one of the
      homologous chromosomes. Molecular analysis showed that the patient had a deletion
      of both alleles of the retinoblastoma (RBI) gene. These results suggest that
      multiple events, including loss of RBI gene function and amplification of a key
      gene(s) on chromosome 21, have contributed to the leukemic transformation.

PMID- 7507705
TI  - Deletion mapping of the short arm of chromosome 3 in human malignant
      mesothelioma.
AB  - Previous cytogenetic investigations have revealed frequent deletions and other
      unbalanced structural rearrangements of 3p in human malignant mesothelioma. We
      have performed a restriction fragment length polymorphism analysis by using the
      polymerase chain reaction and primer sets for seven DNA markers to examine loss
      of heterozygosity (LOH) from 3p in 25 malignant mesotheliomas. Among 24 cases
      informative at one or more 3p loci, 15 (62.5%) exhibited LOH with at least one
      marker. Deletion mapping in these tumors indicates that the common region of
      chromosomal loss resides within band 3p21, in the vicinity of the D3F15S2 locus.
      These results suggest that allelic loss from 3p21 is a frequent occurrence in
      malignant mesothelioma and that one or more putative tumor suppressor genes at
      this site contribute to the pathogenesis of this malignancy.

PMID- 7507706
TI  - Loss of chromosome band 8q24 in sporadic osteocartilaginous exostoses.
AB  - We have karyotyped eight sporadic osteocartilaginous exostoses (OCE), a tumor
      type not characterized cytogenetically before. Five tumors had only normal
      karyotypes, whereas three displayed the following abnormal karyotypes:
      46,XY,del(8)(q24.1); 46,XX,del(8)(q22), t(8;14)(q24.1;q32); and
      46,XY,der(8)t(1;8)(q21;q24),inv(12)(p11q13). All three aberrant cases thus had
      structural rearrangements leading to loss of the distal part of 8q. This is of
      particular interest because multiple OCE are part of the disease phenotype in
      patients with the autosomal dominant tricho-rhino-phalangeal syndrome type II
      (TRP II), many of whom have constitutional loss of genetic material from 8q24.1.
      We hypothesis that band 8q24.1 harbors a tumor suppressor gene, the homozygous
      inactivation of which is important in the genesis of both inherited and sporadic
      OCE. In the familial form, i.e., in TRP II, loss or functional inactivation of
      one allele is inherited and only the second mutation is due to a somatic event,
      whereas both mutations are somatic in the sporadic forms. This hypothesis can be
      tested by analysis of sporadic and inherited OCE for homozygous loss of 8q24
      material with molecular genetic techniques.

PMID- 7507707
TI  - Changes in the concentration of alpha-fetoprotein and placental hormones
      following two methods of medical abortion in early pregnancy.
AB  - OBJECTIVE: Measurement of alpha-fetoprotein (AFP) was used to investigate the
      occurrence of feto-maternal haemorrhage in women undergoing medical abortion.
      DESIGN: Three groups of women with amenorrhoea of 56 or less days were studied. A
      control and a mifepristone group had two blood samples taken 48 h apart. Women
      undergoing medical abortion with gemeprost had two blood samples taken 24 h
      apart. SETTING: Medical Termination Unit, Simpson Memorial Maternity Pavilion,
      Edinburgh. SUBJECTS: Three hundred and thirty-five women requesting abortion.
      INTERVENTIONS: Blood samples taken at 24 h or 48 h apart. MEASUREMENTS AND MAIN
      RESULTS: The rise in concentration of AFP in plasma was much higher (P = 0.01) in
      the two groups of women in whom abortion was induced by gemeprost or mifepristone
      than in control women. Whereas only 5% of women in the control group had a
      significant rise in AFP, 27% and 33% of women in the mifepristone and gemeprost
      groups, respectively, had a rise in AFP level which exceeded the 95th centile (>
      or = 38%). The concentration of hCG rose by 48 h in both control and mifepristone
      groups. Progesterone remained unchanged, and oestradiol decreased (P < 0.02) in
      the mifepristone group. By 24 h, there was a significant fall in the
      concentrations of hCG, progesterone and oestradiol in the group who had aborted
      after being given gemeprost. CONCLUSIONS: Anti-D prophylaxis must be administered
      to rhesus negative women to avoid rhesus iso-immunisation.

PMID- 7507708
TI  - Alpha-fetoprotein in advanced epithelial ovarian cancer.

PMID- 7507709
TI  - Differential regulation of human leukocyte antigen class I genes by interferon in
      vivo and in vitro.
AB  - Modulation of human leukocyte antigen (HLA) class I antigens on peripheral blood
      lymphocytes, monocytes, and hematopoietic precursors during interferon-alpha (IFN
      alpha) therapy was investigated in 18 patients with myeloproliferative syndrome.
      After 1 month of IFN-alpha therapy, an increased number of monocytes and
      hematopoietic precursor cells but not of lymphocytes expressed HLA-DQ antigens.
      In addition, a strong induction of HLA class I antigens was found on both
      hematopoietic progenitors and normal peripheral blood mononuclear cells. By daily
      injections of IFN in the first month of therapy, stimulation continuously
      increased, suggesting a major effect of IFN alpha on hematopoietic progenitors
      with sustained enhanced expression of HLA class I antigens during differentiation
      of myelomonocytic cells. HLA class I antigen expression was consistently
      augmented by IFN alpha in all patients irrespective of their hematologic
      response. Differential in vivo regulation of HLA class I antigens by IFN was
      confirmed by comparison of HLA-A2 with HLA-B antigen expression. In vitro
      expression of the HLA-B7 and -Bw64 genes had been shown earlier to be
      significantly more inducible by IFN than the genes coding for several other HLA
      class I antigens after transfection into mouse L cells. Modification of the 5'
      ends of the HLA-B7 and HLA-B27 genes before transfection in mouse L cells showed
      the presence of enhancer sequences responding to IFN treatment in the 5'
      untranslated region of the HLA-B7 but not of the HLA-B27 gene and suggested the
      presence of independently acting regulatory mechanisms independent of these
      enhancers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507710
TI  - Fas/APO-1 expression and function on malignant cells of hematologic and
      nonhematologic origin.
AB  - Fas/APO-1 is a cell-surface protein capable of inducing apoptosis in a variety of
      cell types upon specific antibody engagement. Antibodies against Fas/APO-1 have
      been used successfully for the treatment of several lymphoid malignancies in
      mice. Before apoptosis triggered by anti-Fas can be fully exploited as a clinical
      therapy, Fas/APO-1 distribution, function, and regulation must be further
      studied. In this study, we analyzed freshly isolated B-cell and T-cell lymphomas
      as well as nonhematological tumor cell lines for Fas/APO-1 expression and
      sensitivity to the growth-inhibitory effects of anti-Fas. Constitutive Fas/APO-1
      was expressed at very low levels on only one of eight B-cell lymphomas analyzed.
      Expression was markedly up-regulated, however, by culture with high-molecular
      weight B-cell growth factor (HMW-BCGF). Fas/APO-1 was constitutively expressed on
      one of two T-cell lymphomas examined at levels comparable to those of activated
      normal lymphocytes. However, neither the B-cell nor T-cell lymphomas positive for
      Fas/APO-1 expression were growth inhibited by anti-Fas. Furthermore, in the case
      of one HMW-BCGF-activated B-cell lymphoma, a significant growth enhancement was
      observed upon anti-Fas treatment. Nonhematologic tumor cell lines showed a
      similar spectrum of biologic responses to anti-Fas, being growth inhibited,
      growth stimulated or unaffected by antibody treatment. In summary, these studies
      suggest that engagement of Fas/APO-1 may trigger a diverse spectrum of biologic
      effects not unlike other members of the nerve growth factor receptor/tumor
      necrosis factor receptor superfamily.

PMID- 7507712
TI  - Midodrine for TCA-induced orthostatic hypotension.

PMID- 7507711
TI  - Use of interleukin-7, interleukin-2, and interferon-gamma to propagate CD4+ T
      cells in culture with maintained antigen specificity.
AB  - In contrast to CD8+ T cells, it has been difficult to establish consistently
      satisfactory conditions for the bulk culture of antitumor CD4+ T cells in either
      mice or humans. This difficulty is not limited to tumor antigen, since similar
      problems are encountered growing CD4+ T cells that recognize alloantigen,
      tetanus, or candida. Four basic findings are reviewed in this article, stemming
      from work with identical results in both human and mouse. (a) Although CD4+ T
      cells initially proliferate after exposure to appropriate antigen-presenting
      cells (APCs), such proliferation is not sustained; however, expansion of CD4+ T
      cells can be achieved with the addition of recombinant interleukin-2 (rIL2) or
      rIL-7. (b) Specific CD4+ responses to antigens are often better sustained with
      exogenous IL-7 than with exogenous IL-2. (c) Adding rIL-7 or rIL-2 permits
      sustained CD4+ T-cell proliferation, but subsequent culture restimulation is
      complicated by high background reactivity to APCs whether APCs are antigen pulsed
      or not; this problem can be overcome by addition of exogenous interferon-gamma
      (IFN-gamma) to the CD4+ cultures. (d) In certain instances proliferation is
      paradoxically impaired by reexposure to specific antigen, possibly reflecting
      apoptosis; this problem is also overcome by addition of rIFN-gamma to culture. We
      conclude that combinations of exogenous IL-7, IL-2, and IFN-gamma with APC
      restimulation can be used to sustain antigen-specific CD4+ T cells in culture.
      Using these techniques, antitumor CD4+ T cells were propagated from the
      peripheral blood of two tumor-bearing patients.

PMID- 7507713
TI  - The failure of newborn mice infected with Escherichia coli to accelerate
      neutrophil production correlates with their failure to increase transcripts for
      granulocyte colony-stimulating factor and interleukin-6.
AB  - We quantified circulating and storage neutrophils, their precursors and
      progenitors, and mRNA for some of the cytokines involved in granulocytopoiesis,
      in newborn and adult mice following intrapulmonary inoculation of Escherichia
      coli. Four hours following inoculation of adult and newborn mice with a quantity
      of organisms 2 logs below the LD100, all animals were neutropenic. After 24 h,
      adults had recovered from the neutropenia but neonates had not (p < 0.001).
      Accelerated neutrophil production was evident in the infected adults, and
      correlated with the appearance of granulocyte colony-stimulating factor (G-CSF)
      transcripts in the liver, spleen, and lung, and interleukin-6 (IL-6) transcripts
      in the spleen and lung. An increase in neutrophil production was not observed in
      the neonates, and none of their organs tested had transcripts for either G-CSF or
      IL-6, but they did have transcripts for cytokines not involved in
      granulocytopoiesis; macrophage colony-stimulating factor and its receptor (c
      fms). We speculate that the failure to increase neutrophil production in infected
      neonatal mice is the result of failure to increase production of relevant
      cytokines.

PMID- 7507714
TI  - Formamidinium-induced dimer stabilization and flicker block behavior in homo- and
      heterodimer channels formed by gramicidin A and N-acetyl gramicidin A.
AB  - Compared to the N-formyl gramicidin A (GA), the N-acetyl gramicidin A (NAG)
      channel has unchanged conductance in 1 M NH4+ (gamma NN/gamma GG = 1, conductance
      ratio) but reduced conductance in 1 M K+ (gamma NN/gamma GG = 0.6) methylammonium
      (gamma NN/gamma GG = 0.3), and formamidinium (gamma NN/gamma GG = 0.1) solutions.
      Except with formamidinium, "flicker blocks" are evident even at low cutoff
      frequencies. For all cations studied, channel lifetimes of N-acetyl homodimers
      (NN) are approximately 50-fold shorter than those of the GA homodimer (GG). The
      novel properties of GA channels in formamidinium solution (supralinear current
      voltage relations and dimer stabilization (Seoh and Busath, 1993)) also appear in
      NN channels. The average single channel lifetime in 1 M formamidinium solution at
      100 mV is 6-7-fold longer than in K+ and methylammonium solutions and, like in
      the GA channel, significantly decreases with increasing membrane potential.
      Experiments with mixtures of the two peptides, GA and NAG, showed three main
      conductance peaks. Oriented hybrids were formed utilizing the principle that
      monomers remain in one leaflet of the bilayer (O'Connell et al., 1990). With GA
      at the polarized side and NAG at the grounded side, at positive potentials (in
      which case hybrids were designated GN) and at negative potentials (in which case
      hybrids were designated NG), channels had the same conductances and channel
      properties at all potentials studied. Flicker blocks were not evident in the
      hybrid channels, which suggests that both N-acetyl methyl groups at the junction
      of the dimer are required to cause flickers. Channel lifetimes in hybrids are
      only approximately threefold shorter than those of the GG channels, and channel
      conductances are similar to those of GG rather than NN channels. We suggest that
      acetyl-acetyl crowding at the dimeric junction in NN channels cause dimer
      destabilization, flickers, and increased selectivity in N-acetyl gramicidin
      channels.

PMID- 7507715
TI  - Energy-minimized conformation of gramicidin-like channels. II. Periodicity of the
      lowest energy conformation of an infinitely long poly-(L,D)-alanine beta 6.3
      helix.
AB  - If an infinitely long polymer has a primary structure characterized by an N
      residue periodicity, a minimum energy conformation of the polymer under the
      constraint of the conformational N-residue periodicity corresponds to an
      equilibrium structure (energy minimal or unstable equilibrium structure) when
      this constraint is absent. Molecular mechanics calculations showed that with an
      infinitely long poly-(L,D)-alanine single-stranded beta 6.3-helix (which has a 2
      residue periodicity with respect to the primary structure), its lowest energy
      conformation within the framework of the conformational 2-residue periodicity is
      also the lowest energy form of this beta 6.3-helix even when no conformational
      periodicity is assumed. In the course of this study, contour maps of helix
      parameters and conformation energies for beta structures of poly-(L,D)-alanine
      were examined. It was also found that beta 6.3-, beta 4.5-, alpha L,D-, and tau
      L,D-helices constitute the global minima in the whole conformational space of
      this polypeptide. In the present calculation, an improved formulation of the
      conformation energy was introduced to estimate the structure and conformation
      energy of an infinite periodic chain from results on a chain of finite length.

PMID- 7507716
TI  - Fast and slow activation of voltage-dependent ion channels in radish vacuoles.
AB  - The molecular processes associated with voltage-dependent opening and closing
      (gating) of ion channels were investigated using a new preparation from plant
      cells, i.e., voltage and calcium-activated ion channels in radish root vacuoles.
      These channels display a main single channel conductance of approximately 90 pS
      and are characterized by long activation times lasting several hundreds of
      milliseconds. Here, we demonstrate that these channels have a second kinetically
      distinct activation mode which is characterized by even longer activation times.
      Different membrane potential protocols allowed to switch between the fast and the
      slow mode in a controlled and reversible manner. At transmembrane potentials of 
      100 mV, the ratio between the fast and slow activation time constant was around
      1:5. Correspondingly, activation times lasting several seconds were observed in
      the slow mode. The molecular process controlling fast and slow activation may
      represent an effective modulator of voltage-dependent gating of ion channels in
      other plant and animal systems.

PMID- 7507717
TI  - Patch clamp studies of single intact secretory granules.
AB  - The membrane of secretory granules is involved in the molecular events that cause
      exocytotic fusion. Several of the proteins that have been purified from the
      membrane of secretory granules form ion channels when they are reconstituted in
      lipid bilayers and, therefore, have been thought to form part of the molecular
      structure of the exocytotic fusion pore. We have used the patch clamp technique
      to study ion conductances in single isolated secretory granules from beige mouse
      mast cells. We found that the membrane of the intact granule had a conductance of
      < 50 pS. No abrupt changes in current corresponding to the opening and closing of
      ion channels were observed, even under conditions where exocytotic fusion
      occurred. However, mechanical tension or a large voltage pulse caused the
      breakdown of the granule membrane resulting in the abrupt opening of a pore with
      an ion conductance of about 1 nS that fluctuated rapidly and could expand to an
      immeasurably large conductance or close completely. Surprisingly, the behavior of
      these pores resembled the pattern of conductance changes of exocytotic fusion
      pores observed in degranulating beige mast cells. This similarity supports the
      view that the earliest fusion pore is formed upon the breakdown of a bilayer such
      as that formed during hemifusion.

PMID- 7507718
TI  - Probing alamethicin channels with water-soluble polymers. Size-modulated osmotic
      action.
AB  - Contrary to expectations based on heightened solution viscosity, alamethicin
      channels appear to speed up in the presence of water soluble polyethylene glycols
      (PEGs) and dextrans. Specifically, added polymers reduce the probabilities of
      transition to higher-conductance states but do not change channel lifetimes. They
      thereby shorten the duration of current "bursts." These modified probabilities
      and kinetics reveal the action of polymer osmotic stress to suppress channel
      formation. The osmotic action of large, fully excluded polymers shows that some
      3,000 A3 of water are taken up by the channel from the solution upon each
      transition to an adjacent higher-conductance state. The partial osmotic action of
      incompletely excluded polymers reveals the extent of exclusion for different-size
      polymers. The partial exclusion thus measured agrees remarkably well with
      estimates using data on reduction of single-channel conductance by current
      impeding polymers. One can relate the degree of each polymer's exclusion to its
      size and to the radius of the channel pore.

PMID- 7507720
TI  - Fluorescence depletion measurements in various experimental geometries provide
      true emission and absorption anisotropies for the study of protein rotation.
AB  - Use of fluorescence depletion methods for measuring slow protein rotational
      diffusion has been limited by failure to obtain, from depletion data, well
      defined anisotropy functions dependent on the distribution of either fluorophore
      emission or absorption transition dipoles, but not both. Such anisotropies would
      be directly comparable to those obtained from phosphorescence emission or triplet
      absorption measurements. We now describe such procedures applicable to cuvet and
      microscope experimental geometries, together with supporting experimental
      results. In cuvet measurements, the pump and probe beams are colinear and
      fluorescence is collected at 90 degrees to this axis. The data analysis procedure
      for this geometry has been suggested by Wegener (Biophys. J., 46 (1984) 795) and
      permits calculation of the absorption and emission anisotropies and the
      interdipole angle. In microscope experiments, fluorescence emission is collected
      along the pump/probe beam axis. For microscope measurements, a new experimental
      procedure permits evaluation of absorption and emission anisotropies when the
      interdipole angle is independently known. In either case multiple depletion
      measurements are required, each with different relative orientations of the probe
      beam polarization, pump beam polarization and emission polarizer axis. We have
      used these methods to calculate the time-dependent anisotropies for eosin
      derivatized BSA rotation in glycerol solutions in both experimental geometries.
      These data correspond well with those obtained from time-resolved phosphorescence
      anisotropy measurements.

PMID- 7507721
TI  - The role of endocardial endothelium in the modulation of myocardial contraction
      in the isolated whole heart.
AB  - Selective damage to the endocardial endothelium in isolated papillary muscle
      preparations has been shown to produce an abbreviation of contraction, changes
      which were also observed following an increase in myocardial cyclic GMP in those
      preparations. In the present study we have investigated the effects of removing
      the endocardium and increasing myocardial cyclic GMP on contractile parameters in
      isolated Langendorff perfused ferret hearts, where the myocardial mass underlying
      the endocardium is much greater. Selective damage to left ventricular endocardial
      endothelium without damaging the underlying myocardium was achieved by brief
      exposure to a weak detergent solution (Triton X-100 0.005% v/v). This resulted in
      a significant abbreviation of the left ventricular pressure-time curve due to the
      earlier onset of relaxation, but there was little effect on early systole. The
      direct intraventricular infusion for 15 minutes of 10 microM sodium
      nitroprusside, a donor of nitric oxide, or of 1 microM substance P, to stimulate
      release of endothelium-derived relaxing factor, did not increase myocardial
      cyclic GMP levels or alter left ventricular contractile performance. Myocardial
      cyclic GMP levels were significantly increased by 15 minute intracoronary
      infusions of 10 microM nitroprusside and 1 microM substance P, approximately ten
      fold and two-fold respectively. Intracoronary nitroprusside induced an
      abbreviation of the left ventricular pressure-time curve with an earlier onset of
      relaxation, but contraction was unaltered by intracoronary substance P. These
      results show that, in the isolated Langendorff perfused ferret heart, both
      selective removal of endocardial endothelium and an increase in myocardial cyclic
      GMP cause an abbreviation of left ventricular pressure and an earlier onset of
      relaxation with little change in early systole.

PMID- 7507719
TI  - An electron spin resonance study of interactions between gramicidin A' and
      phosphatidylcholine bilayers.
AB  - The model of microscopic order and macroscopic disorder was used to stimulate
      electron spin resonance spectra of spin-labeled lipids, 5-PC, 10-PC, and 16-PC in
      multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC) containing
      gramicidin A' (GA) at temperatures above the gel-to-liquid crystal transition of
      DPPC. The simulations show that at a lower concentration of GA (i.e., molar
      ratios of DPPC/GA greater than 3), GA has only a slight effect on the acyl chain
      dynamics. The rotational diffusion rate around the axis parallel to the long
      hydrocarbon chain remains unchanged or increases slightly, while the rate around
      the perpendicular axes decreases slightly. These spectra from DPPC/GA mixtures
      could only be fit successfully with two or more components consistent with the
      well-known concept of "boundary lipids," that is, the peptide induces structural
      inhomogeneity in lipid bilayers. However, the spectra were significantly better
      fit with additional components that exhibit increased local ordering, implying
      decreased amplitude of rotational motion, rather than immobilized components with
      sharply a reduced rotational rate. The largest relative effects occur at the end
      of the acyl chains, where the average local order parameter St of 16-PC increases
      from 0.06 for pure lipid to 0.66 for 1:1 DPPC/GA. The inhomogeneity in ordering
      in DPPC bilayers due to GA decreases with increasing temperature. The hyperfine
      tensor component Azz increases for 10-PC and 16-PC when GA is incorporated into
      DPPC bilayers, indicating that water has deeply penetrated into the DPPC
      bilayers. Simulations of published electron spin resonance spectra of 14-PC in
      dimyristoylphosphatidylcholine/cytochrome oxidase complexes were also better fit
      by additional components that were more ordered, rather than immobilized. The
      average local order parameter in this case is found to increase from 0.11 for
      pure dimyristoylphosphatidylcholine to 0.61 for a lipid/protein ratio of 50.
      These spectra and their simulations are similar to the results obtained with 16
      PC in the DPPC/GA mixtures. The relevance to studies of lipid-protein
      interactions for other proteins is briefly discussed.

PMID- 7507723
TI  - Protection against light-induced retinal degeneration by an inhibitor of NO
      synthase.
AB  - The existence of nitric oxide synthase (NOS) in retinal rod outer segments and
      pigmented epithelial cells suggests that NO in excess could impair the
      interaction between these cells, resulting in photoreceptor degeneration. To test
      this hypothesis, NG-nitro-L-arginine methyl ester (L-NAME), an NOS inhibitor, was
      intraperitoneally injected daily into rats subjected to constant illumination for
      7 days in order to destroy their photoreceptors. By measuring photoreceptor
      nuclear layer thicknesses, we found that L-NAME partially protects (by up to 35%)
      against the degeneration of photoreceptors and acts to maintain their
      organization. Thus NO may be involved in the process by which photoreceptor
      degeneration results from constant illumination of the retina.

PMID- 7507724
TI  - Expression of 25(OH) vitamin D3 24-hydroxylase gene in glial cells.
AB  - The expression of the 25(OH) vitamin D3 24-hydroxylase gene was studied in C6
      glioma and rat primary glial cell culture. The expression of the 25(OH)D3 24
      hydroxylase gene was not detected in C6 glioma or glial cells cultured in a serum
      free medium. However, the 25(OH)D3 24-hydroxylase mRNA was induced in a dose
      dependent manner in cells treated with 1,25(OH)2D3. These findings provide
      further evidence for an involvement of vitamin D3 metabolites in brain function.

PMID- 7507725
TI  - Modulation of the neurotensin striato-nigral pathway by D1 receptors.
AB  - It has been reported that methamphetamine (METH) upregulates striatal neurotensin
      (NT) mRNA levels. The present in situ hybridization study demonstrates, using the
      dopamine D1 antagonist SCH23390 that this effect is mediated through D1
      receptors. Sulpiride, a selective D2 antagonist, induces an upregulation of NT
      expression, which in some striatal areas is additive to the METH effect. This
      suggests the existence of at least two NT striatal neuronal populations. One,
      sensitive to D1 receptors, corresponds to the recently described striatonigral NT
      pathway. The second one, modulated by D2 receptors, may project to the globus
      pallidus and/or represent interneurones.

PMID- 7507722
TI  - Neostriatal GABAergic interneurones contain NOS, calretinin or parvalbumin.
AB  - To reveal functional heterogeneity among GABAergic interneurones in rat
      neostriatum, we investigated: (1) whether nitric oxide synthase (NOS)- and
      calretinin-immunoreactive cells, like parvalbumin-immunoreactive cells, were also
      immunoreactive for 67 kD glutamic acid decarboxylase (GAD67) and GABA; (2)
      whether NOS cells, calretinin cells and parvalbumin cells belonged to separate
      populations or not. NOS cells, calretinin cells and parvalbumin cells all showed
      immunoreactivity for GAD67 in colchicine-treated rats. Calretinin cells and
      parvalbumin cells were also immunoreactive for GABA. Only a few cells (0-3%)
      showed immunoreactivity for two antigens. These results suggest that the
      neostriatum has at least three GABAergic interneuronal systems.

PMID- 7507726
TI  - Stoichiometry of a recombinant GABAA receptor deduced from mutation-induced
      rectification.
AB  - Ligand-gated ion channels generally display a heterooligomeric subunit structure.
      The present report describes an electrophysiological method that provides
      criteria indicating the subunit stoichiometry of a recombinant GABAA receptor
      composed of alpha 3, beta 2 and gamma 2 subunits. Our results exclude the
      stoichiometries 3 alpha 1 beta 1 gamma, 1 alpha 3 beta 1 gamma, 1 alpha 1 beta 3
      gamma and suggest that the possible subunit stoichiometries for this receptor are
      2 alpha 1 beta 2 gamma, 2 alpha 2 beta 1 gamma or 1 alpha 2 beta 2 gamma, of
      which the alpha subunit composition 2 alpha 1 beta 2 gamma may be favoured. The
      method is based on the quantification of the outward rectification of the GABA
      evoked current induced by point mutation of charged amino acids located near the
      ion channel pore.

PMID- 7507727
TI  - A new monoclonal antibody against the anionic domain of the amyloid precursor
      protein of Alzheimer's disease.
AB  - A new mouse monoclonal antibody was raised to a bacterial fusion protein between
      beta-galactosidase and the extracellular domain of the human amyloid protein
      precursor (APP). In immunoblotting experiments, this monoclonal antibody labelled
      the bacterial fusion protein used as an immunogen, the human brain APP, and
      different full-length APP isoforms expressed by transfected cells. In
      immunocytochemistry, the monoclonal antibody stained the dystrophic neurites of
      abundant senile plaques found in the cerebral cortex of patients with Alzheimer's
      disease. Using bacterial expression of several cDNA fragments, the epitope was
      mapped to an amino acid sequence of APP not investigated before.

PMID- 7507728
TI  - Increased frequency of NGF in sera of rheumatoid arthritis and systemic lupus
      erythematosus patients.
AB  - Nerve growth factor (NGF) levels were measured by a two-site enzyme-linked
      immunosorbent assay (ELISA) in sera of patients with three autoimmune diseases,
      rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and thyroiditis.
      Serum NGF levels were variable (15 pg ml(-1)-1.6 ng ml-1) but not significantly
      different among these groups compared with control subjects. However the
      frequency of detectable circulating NGF was significantly higher in RA and SLE
      patients but not in thyroiditis patients compared with controls. The present data
      provides evidence for NGF involvement in two autoimmune rheumatic diseases and
      suggests a possible differential role of NGF as immunomodulatory agent in
      systemic versus certain organ-specific autoimmune diseases.

PMID- 7507729
TI  - Mobilization of tumor cells and hematopoietic progenitor cells into peripheral
      blood of patients with solid tumors.
AB  - Peripheral blood progenitor cells (PBPCs) are increasingly used for autografting
      after high-dose chemotherapy. One advantage of PBPCs over the use of autologous
      bone marrow would be a reduced risk of tumor-cell contamination. However, the
      actual level of tumor cells contaminating PBPC harvests is poorly investigated.
      It is currently not known whether mobilization of PBPCs might also result in
      mobilization of tumor cells. We evaluated 358 peripheral blood samples from 46
      patients with stage IV or high-risk stage II/III breast cancer, small cell (SCLC)
      or non-small cell (NSCLC) lung cancer, as well as other advanced malignancies for
      the detection of epithelial tumor cells. Monoclonal antibodies against acidic and
      basic cytokeratin components and epithelial antigens (HEA) were used in an
      alkaline phosphatase-anti-alkaline phosphatase assay with a sensitivity of 1
      tumor cell within 4 x 10(5) total cells. Before initiation of PBPC mobilization,
      circulating tumor cells were detected in 2/7 (29%) patients with stage IV breast
      cancer and in 2/10 (20%) patients with extensive-disease SCLC, respectively. In
      these patients, an even higher number of circulating tumor cells was detected
      after chemotherapy with VP16, ifosfamide, and cisplatin (VIP) followed by
      granulocyte colony-stimulating factor (G-CSF). This approach has previously been
      shown to be highly effective in mobilizing PBPCs. In the 42 patients without
      circulating tumor cells during steady state, tumor cells were mobilized in 9/42
      (21%) patients after VIP+G-CSF induced recruitment of PBPCs. The overall
      incidence of tumor cells varied between 4 and 5,600 per 1.6 x 10(6) mononuclear
      cells analyzed. All stage IV breast cancer patients and 50% of SCLC patients were
      found to concomitantly mobilize tumor cells and PBPCs. Kinetic analyses showed
      two patterns of tumor cell recruitment depending on the presence or absence of
      bone marrow disease: (1) early after chemotherapy (between days 1 and 7) in
      patients without marrow infiltration, and (2) between days 9 and 16 in patients
      with marrow infiltration, ie, within the optimal time period for the collection
      of PBPCs. We show that there is a high proportion of patients with circulating
      tumor cells under steady-state conditions, and in addition a substantial risk of
      concomitant tumor cell recruitment upon mobilization of PBPCs, particularly in
      stage IV breast cancer patients with bone marrow infiltration. The biologic and
      clinical significance of this finding is unknown at present.

PMID- 7507730
TI  - CD44 mediates hyaluronan binding by human myeloid KG1A and KG1 cells.
AB  - Hyaluronan-binding function of the CD44 molecule has not been so far detected in
      myeloid cells. To study pure populations of primitive myeloid cells, we
      investigated the hyaluronan-binding function of the CD44 molecule from three
      myeloid cell lines: KG1a, KG1, and HL60. Both KG1a and KG1 cells express the CD34
      antigen characteristic of the hematopoietic stem cells and HL60 cells do not;
      accordingly, KG1a and KG1 cells are generally considered as the most primitive
      and HL60 cells as the most mature of these cell lines. Measurement of cell
      adhesion to hyaluronan-coated surfaces (using 51Cr-labeled cells) and of
      aggregate formation in hyaluronan-containing solutions, showed that 45% of KG1
      cells and 22% to 24% of KG1a spontaneously bind to hyaluronan, whereas HL60 cells
      do not either spontaneously or after treatment with a phorbol ester. Hyaluronan
      binding by KG1a and KG1 cells is mediated by CD44, because it is specifically
      abolished by monoclonal antibodies (MoAbs) to this molecule. The binding might
      require phosphorylation by protein kinase C and perhaps also by protein kinase A,
      because it is prevented by staurosporine, which inhibits these enzymes. 12-O
      tetradecanoylphorbol-13-acetate (TPA) which activates protein kinase C, rises to
      80% the proportion of KG1 and KG1a cells that bind hyaluronan; this activation is
      dependent on protein synthesis, for it is abrogated by cyclophosphamide, a
      protein synthesis inhibitor. Binding of TPA-treated cells to hyaluronan is only
      partly inhibited by MoAb to CD44: this suggests that TPA may induce synthesis of
      a hyaluronan-binding protein distinct from CD44. Considering the abundance of
      hyaluronan in human bone marrow, these results suggest that CD44 may be involved
      in mediating precursor-stroma interaction.

PMID- 7507731
TI  - Circulating monoclonal B cells expressing P glycoprotein may be a reservoir of
      multidrug-resistant disease in multiple myeloma.
AB  - Multiple myeloma is basically an incurable cancer. Most patients respond
      initially to chemotherapy with reduction in bone marrow (BM) plasma cells and
      monoclonal Ig levels, but the disease nearly always recurs and becomes refractory
      to therapy. The objective of this study was to characterize the expression of the
      multidrug transport pump, P-glycoprotein 170 (P-gp), in myeloma. The great
      majority of B cells from peripheral blood mononuclear cells (PBMCs) in myeloma
      express P-gp, detected by the monoclonal antibody MRK-16. P-gp+ blood B cells
      exhibit extensive DNA hyperdiploidy, suggesting replicative abnormality
      characteristic of malignant growth. We speculate these represent a stem cell
      population in myeloma. The proportion of B cells expressing P-gp was comparable
      among untreated myeloma patients and those treated with chemotherapy, biologic
      response modifiers, or off treatment. Among BM cells, P-gp was absent or low in
      untreated myeloma patients but was expressed at high levels on BM cells from
      patients previously treated with chemotherapy. For untreated patients the
      majority of B/plasma cells expressing P-gp are located in PBMCs, not the BM
      cells. Flow cytometric analysis of rhodamine 123 dye efflux indicated a
      functional P-gp that was efficiently blocked by verapamil or cyclosporin A (CsA).
      Both the CD11bhi CD19+ B cells and the T cells in myeloma PBMCs had active CsA
      inhibited dye efflux, but monocytes lacked the ability to efflux dye. Nearly all
      CD38hi plasma cells from myeloma BM cells retained dye, indicating their lack of
      a functional transport pump. Thus, PBMC B cells may be the predominant set of
      drug-resistant tumor cells. Myeloma PBMC B cells were cultured with Adriamycin
      with or without CsA and drug toxicity evaluated by the induction of apoptosis,
      using flow cytometry to quantitate DNA disruption. No apoptosis was detectable at
      0.01 microgram/mL adriamycin, the in vivo steady-state level, with or without
      CsA. With 0.1 microgram adriamycin, no apoptosis was detectable in the absence of
      CsA, but with CsA, 66% of B cells initiated DNA disruption, whereas most T cells
      were spared. This work suggests that currently used drug dosages are too low to
      effect P-gp+ B-cell death, even in the presence of CsA. We suggest that blood B
      cells comprise a highly drug-resistant subset of the myeloma B lineage that
      escapes conventional chemotherapy and may underlie the almost uniform fatal
      relapse in myeloma patients.

PMID- 7507733
TI  - Expression of the c-kit receptor in human lymphomas is restricted to Hodgkin's
      disease and CD30+ anaplastic large cell lymphomas.
AB  - The product of the proto-oncogene c-kit is a transmembrane receptor protein that
      plays an important role in the regulation of normal and neoplastic hematopoiesis
      via the interaction with its specific ligand termed stem cell factor. To examine
      whether c-kit product is possibly involved in the pathogenesis of human
      lymphomas, we analyzed the expression of the c-kit protein in neoplastic cells
      from a variety of lymphoid tumors by immunostaining of lymph node frozen sections
      with the 17F11 antibody, detecting an extracellular epitope of the c-kit
      receptor, and of c-kit RNA by Northern blot hybridization. Of 24 nonHodgkin's
      lymphomas (NHL) of B- and T-cell phenotype, none expressed immunodetectable c-kit
      protein that was also not evidenced in lymphoid cells of reactive lymph nodes and
      normal tonsils. In contrast, c-kit protein was expressed by Reed-Sternberg cells
      and their mononuclear variants from 11 of 21 Hodgkin's disease (HD) cases, and in
      tumor cells from 11 of 16 cases of CD30+ anaplastic large cell lymphoma (ALCL). c
      kit specific mRNA was also detected in lymph node tissues from HD and ALCL cases
      but not in neoplastic tissues from NHL other than ALCL. In addition, c-kit/CD30+
      tumor cells were evidenced by flow cytometry in a patient displaying massive bone
      marrow involvement by ALCL. With the exclusion of lymphocyte predominance cases
      of HD that resulted c-kit expression and the other histologic subtypes of HD or
      the immunologic phenotype of tumor cells (B, T, nonB-nonT) in both HD and ALCL.
      The highly restricted expression of the c-kit product among human lymphomas to HD
      and ALCL provides a further biologic link between these two closely related
      lymphoma entities.

PMID- 7507732
TI  - Adhesion-dependent survival of normal and leukemic human B lymphoblasts on bone
      marrow stromal cells.
AB  - We investigated the requirement for intimate contact between bone marrow stroma
      and B lymphoblasts from normal donors and children with leukemia. By scanning
      electron microscopy, both normal and leukemic cells seeded onto stroma were
      surrounded by folds of stromal cells or were linked to the stroma by fine
      tendrils and uropods. Separation of normal B progenitors from stroma by use of
      microporous membranes led to significantly lower cell recoveries compared with
      results when contact was unimpeded. For instance, 22.5% +/- 1.8% (mean +/- SEM)
      of CD19+, CD34+ cells (most immature subset) were recovered after a 7-day culture
      directly on stroma, compared with 5.2% +/- 0.7% after growth on membranes (P <
      .001 by Student's t test). In 6 of 11 cases of B-lineage acute lymphoblastic
      leukemia, separation of progenitors from stroma resulted in apoptosis and a
      greater than 60% reduction in cell recovery. In the remaining 5 cases, however,
      this effect was much less pronounced, with reductions in cell recoveries ranging
      from 48.5% to less than 1% (median, 39.0%) of control values. Inhibition of very
      late antigen-4, a surface molecule critical for adhesion of B lymphoblasts to
      stroma, was associated with a greater loss of normal CD34+ B progenitors compared
      with that for equivalent leukemic cells. These results establish direct contact
      with stroma as a survival requirement of normal B lymphoblasts and show marked
      heterogeneity in stromal dependency among B-lineage leukemic cells.

PMID- 7507734
TI  - In vivo expression of the B7 costimulatory molecule by subsets of antigen
      presenting cells and the malignant cells of Hodgkin's disease.
AB  - The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in
      vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28
      present on the latter cells. In this study, benign lymphoid tissues, lymphomas,
      and extralymphoid inflammatory sites were examined immunohistochemically using
      anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign
      transformed germinal center B cells, as it was by B cells of follicular
      lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of
      macrophages and dendritic cells in a variety of lymphoid tissues. It was present
      in abundance on all macrophages constituting sarcoid granulomas in lymph nodes.
      In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only
      weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of
      Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that
      potentially contributes to the lymphocytic accumulation that is a feature of this
      condition. CD28+ T cells were seen in all areas where T cells were present. B7+
      and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node
      paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a
      potential for cellular interaction via these molecules at these sites.

PMID- 7507735
TI  - Glycosyl-phosphatidylinositol anchor synthesis in paroxysmal nocturnal
      hemoglobinuria: partial or complete defect in an early step.
AB  - The defect in the biosynthesis of the glycosyl-phosphatidyl inositol (GPI) anchor
      in paroxysmal nocturnal hemoglobinuria (PNH) appears to be in the initial steps.
      In biosynthetic studies using [3H]mannose, abnormal granulocytes of eight
      patients, and B lymphocytes transformed by Epstein-Barr virus of six different
      patients synthesized dolichyl phosphoryl mannose, but little or no later
      mannosylated intermediates. When fused with murine cell lines known to be
      deficient at different biosynthetic steps of the GPI anchor, the GPI-anchor
      deficient granulocytes of 21/21 patients and lymphocytes from 6/6 patients
      complemented all murine cell lines except those of class A; cells of this class
      are not able to add N-acetylglucosamine to phosphatidylinositol. These studies
      indicate that the defect in GPI-anchor synthesis in PNH is early in the pathway,
      and is the same as that of class A mutants, but may be partial in some patients,
      resulting in the production of small amounts of mannosylated intermediates.

PMID- 7507737
TI  - Defective regulation of complement by the sickle erythrocyte: evidence for a
      defect in control of membrane attack complex formation.
AB  - A prominent clinical manifestation of sickle cell disease (SCD) is hemolytic
      anemia. Although complement activation can lead to intravascular hemolysis, its
      role in the hemolysis of SCD is not known. Because normal red blood cells induced
      to vesiculate by treatment with calcium and ionophore become sensitive to damage
      by activated complement and because sickle cells release microvesicles as they
      circulate, we postulated that sickle cells might also be unusually sensitive to
      complement-dependent hemolysis. Complement activation is tightly regulated on the
      membrane of the normal erythrocyte; therefore, defective complement regulation by
      the sickle cell would be necessary for complement-dependent hemolysis to occur.
      These studies show a defect in the regulation of membrane attack complex (C5b-9)
      formation in sickle erythrocytes, particularly in the most dense cells. The
      defect is characterized by increased binding of C5b-7 and of C9 to denser sickle
      cells and results in increased susceptibility of sickle cells to C5b-9-mediated
      (reactive) lysis initiated by either C5b6 or activated cobra venom factor. Among
      the densest sickle cells, irreversibly sickled cells are especially sensitive to
      reactive lysis. The similarity of this defect to that previously described in a
      patient with paroxysmal nocturnal hemoglobinuria suggests that complement
      mediated hemolysis could play a role in the anemia of SCD.

PMID- 7507736
TI  - A novel deletion of approximately 27 kb including the beta-globin gene and the
      locus control region 3'HS-1 regulatory sequence: beta zero-thalassemia or
      hereditary persistence of fetal hemoglobin?
AB  - A novel deletion of approximately 27 kb with the 5' breakpoint 1.5 to 2.2 kb
      upstream of the beta-globin gene, and the 3' breakpoint approximately 24 kb
      downstream of the beta-globin gene, has been found in five members of two
      families from Southeast Asia (Vietnam and Cambodia). Six members of another
      family from China, previously reported from our laboratory, have also been shown
      to carry this deletion. The patients presented with mild hypochromia and
      microcytosis, a hemoglobin (Hb) A2 level of approximately 4.0%, and a markedly
      increased, heterocellularly distributed, Hb F level (14.0 to 26.0%). In vitro
      globin-chain synthesis showed a mild imbalance with appreciable gamma-chain
      compensation (alpha/beta + gamma ratio of 1.46). The 3' end of this deletion
      includes the 3'HS-1, and we hypothesize that removal of this region results in
      the loss of its gamma-globin gene-silencing effect, which causes a markedly
      elevated Hb F level with a modest increase in Hb A2 levels, unlike the situation
      in other deletional beta zero-thalassemias. The possible influence of particular
      sequence variations in the locus control region 5'HS-2 and the G gamma promoter,
      present on the chromosome with this deletion, on the overall gamma-globin gene
      should also be considered.

PMID- 7507738
TI  - Peripheral blood cells are predominantly chimeric of affected and normal cells in
      patients with paroxysmal nocturnal hemoglobinuria: simultaneous investigation on
      clonality and expression of glycophosphatidylinositol-anchored proteins.
AB  - To investigate clonal compositions of hematologic cells in paroxysmal nocturnal
      hemoglobinuria (PNH), we analyzed peripheral blood (PB) cells of 12 female
      patients with PNH, by clonality analysis using X-chromosome inactivation and
      assessment of expression of glycophosphatidylinositol-anchored proteins (GPI-APs)
      by flow cytometry. Southern hybridization showed that granulocytes were
      monoclonal in three and polyclonal in eight patients, respectively, whereas
      lymphocytes were polyclonal in all nine patients examined. Expressions of CD16
      and CD59 on granulocytes varied greatly in seven patients examined. Clonality
      analysis of granulocytes by the polymerase chain reaction showed that CD59- and
      CD59low+ cells were monoclonal, whereas CD59+ cells were polyclonal. It was shown
      that PB cells are predominantly chimeric of clonal (GPI-AP- or GPI-APlow+) and
      nonclonal (GPI-AP+) cells in PNH, and that degrees of chimerism differ greatly
      from patient to patient.

PMID- 7507740
TI  - The poncho graft and root-form implants.

PMID- 7507739
TI  - A novel form of congenital dyserythropoietic anemia associated with deficiency of
      erythroid CD44 and a unique blood group phenotype [In(a-b-), Co(a-b-)].
AB  - We have used a panel of well-characterized monoclonal antibodies (MoAbs) to
      examine the blood cells of a patient with a novel form of congenital
      dyserythropoietic anemia (CDA) characterized by intra-erythroblastic and intra
      erythrocytic membranous inclusions. Twelve antibodies defining three
      nonoverlapping epitope groups on the extracellular domain of CD44 all failed to
      react with the red blood cells (RBCs) of the patient. A rabbit antibody to the
      cytoplasmic domain of CD44 from normal RBCs failed to react with the patient's
      RBC ghosts. In contrast, the patient's lymphocytes, granulocytes, and monocytes
      showed apparently normal CD44 expression. Bone marrow preparations stained with
      CD44 antibodies and visualized with 125I antimouse Ig (F(ab')2) followed by
      autoradiography showed positive staining of lymphocytes and myeloid cells but not
      of most orthotolidine-positive erythroblasts. The patient's RBCs also gave weaker
      than normal reactions with MoAbs of anti-LWab specificity while MoAbs to
      glycophorins A, B, and C, Rh polypeptides, CD47, CD55, CD58, CD59,
      acetylcholinesterase, and Lutheran and Kell glycoproteins all gave normal
      reactions. Agglutination tests with human blood grouping sera demonstrated that
      the RBCs of the patient have the unique phenotype In(a-b-), Co(a-b-) and that
      they also lack the high incidence RBC antigen AnWj. The phenotype In(a-b-) would
      be expected because these antigens are known to be expressed on CD44. There is
      also some evidence associating the AnWj antigen with CD44. However, the CO blood
      group locus is on chromosome 7p whereas that for CD44 is on chromosome 11p.
      Quantitative binding assays using 125I-labeled Fab fragments of CD44 antibodies
      did not show any evidence for reduced levels of CD44 on RBCs from the parents of
      the patient or from her unaffected sister. The parents and sister had the common
      Colton blood group phenotype [Co(a+b-)]. Neither deficiency of CD44 nor absence
      of Colton antigens are general features of CDA because erythrocytes from patients
      with CDA I, CDA II, CDA III, and two other unclassified CDAs had normal
      expression of CD44 and normal Colton blood group phenotypes. Further analysis of
      the defect(s) present in the patient's erythroid cells may provide useful
      information regarding membrane assembly and the regulation of differentiation in
      normal erythroid cells.

PMID- 7507741
TI  - Antiproliferative effects and DNA hypomethylation by 5-aza-2'-deoxycytidine in
      human neuroblastoma cell lines.
AB  - 5-Aza-2'-deoxycytidine (5-AZA-CdR) is an inhibitor of DNA methylation, and its
      antileukemic activity has been shown in preclinical and clinical studies. This
      paper describes the ability of 5-AZA-CdR to inhibit DNA methylation, DNA
      synthesis and cell growth in several human neuroblastoma cell lines. The
      stability of cell growth inhibition was ascertained, as well as the ability of
      the metabolite thymidine to enhance the antiproliferative effect of 5-AZA-CdR.
      The activity of phosphorylating enzyme deoxycytidine kinase (dCK) was correlated
      to different levels of sensitivity in several cell lines. The results obtained
      indicate that 5-AZA-CdR may be an agent for the chemotherapy of neuroblastoma.

PMID- 7507742
TI  - An in vitro pharmacological model of vascular smooth muscle.
AB  - In order to develop an in vitro model of vascular tissue for pharmacological
      studies, segments of porcine coronary arteries were incubated in culture media
      under sterile conditions in cell culture incubator at 37 degrees C with 95% O2 +
      5% CO2. After 3 days of incubation, changes in isometric tension were measured in
      vascular rings and compared with the fresh tissue. KCl (10-75 mM) and
      prostaglandin F2 alpha (1-20 microM) produced a similar concentration-dependent
      contraction in the incubated and fresh arteries. The concentration-dependent
      relaxation curves produced by 2-chloroadenosine (10(-8) to 10(-4) M) and
      isoproterenol (10(-8) to 10(-5) M) were unaltered in the incubated tissue versus
      fresh. Similarly, the relaxation responses to forskolin and sodium nitroprusside
      (10(-8) to 10(-5) M) were unaffected in the incubated arteries. The relaxations
      produced by substance P (10(-12) to 10(-8) M) and bradykinin (10(-7) M)--the
      endothelium-dependent agents--were also unaltered in the incubated rings versus
      fresh. Therefore, we conclude that after the incubation of porcine coronary
      artery for 3 days, the contraction/relaxation responses to various agonists
      acting through different mechanisms were unaltered in porcine coronary artery.
      This in vitro model of vascular smooth muscle provides a potential for
      pharmacological and toxicological studies.

PMID- 7507743
TI  - Proteoglycans in male reproductive tract.
AB  - Proteoglycans in male reproductive tract have been mainly characterized in
      testicular extracellular matrix and somatic cells. Heparan sulfate, chondroitin
      sulfate and hybrid chondroitin/heparan sulfate proteoglycans coexist within the
      testes. Their biological roles are not currently established, however, the
      molecular characterization of some of them is indicative that they might be
      involved in various regulatory processes during spermatogenesis.

PMID- 7507744
TI  - Is there an interspecific diversity of the thymic microenvironment?
AB  - Thymic epithelial cells (TEC) heterogeneity suggests the existence of functional
      subsets. Anti-cytokeratin (Anti-CK) monoclonal antibodies (MAb), markers of
      epithelial differentiation, have been used to detect TEC subsets in rodents and
      humans. These MAb revealed a different topography of CK-defined TEC subsets in
      mice and humans, leading us to carry out a comparative study of mammalian
      thymuses. Our study showed that the distribution pattern of cytokeratins in the
      thymic epithelium is complex and unique, with coexpression of CK typical of
      simple and stratified epithelia. Moreover, we demonstrated an interspecific
      diversity of CK expression within the thymic lobules. Interestingly, such
      diversity was not a general phenomenon for the expression of any thymic
      microenvironmental proteins, because the location of extracellular matrix
      components was essentially similar in the mammalian species studied.

PMID- 7507745
TI  - Modulation of cytokeratin expression in the hamster thymus: evidence for a
      plasticity of the thymic epithelium.
AB  - Cytokeratin (CK) expression was investigated, by means of immunocytochemistry, in
      the hamster thymic epithelium during ontogeny, as well as in primary cultures and
      upon glucocorticoid hormone treatment in vivo. As compared to the distribution
      pattern of distinct monoclonal antibody-defined cytokeratins in the normal adult
      thymus, CK modulation was evidenced in the three situations studied. During
      thymus ontogeny, both cytokeratins of simple lining epithelia, as CK8 and CK18,
      as well as the CK1/CK10 pair (typical marker of terminal stage of
      keratinization), were expressed since early stages of thymus development. They
      were located in the central region of thymic lobules preceding the cortical
      medullary distinctions. This differed from what had been previously shown for
      mouse thymus ontogeny, revealing that the interspecific diversity in the
      distribution pattern of thymic cytokeratins occurred early in fetal life. A
      modulation of CK expression was also detected when hamster thymic epithelial
      cells (TEC) were led to grow in culture, with a down-regulation of CK19
      contrasting with an enhancement of CK18 expression. This diverged from the
      maintenance of the in situ pattern when human TEC were cultured. Last, in vivo
      hydrocortisone treatment, known to increase the numbers of KL1+ cells in the
      mouse thymus medulla, promoted a cortical expression of the CK1/CK10 pair in the
      hamster thymus. Taken together, our findings demonstrate a continuous plasticity
      of the thymic epithelium, at least regarding cytokeratin expression, and enlarge
      the concept of interspecific diversity of intrathymic CK distribution in
      conditions as morphogenesis, in vitro system, and responsiveness to
      glucocorticoid hormone treatment.

PMID- 7507746
TI  - Monoclonal antibody against a lactose epitope of glycosphingolipids binds to
      melanoma tumour cells.
AB  - Mice were immunized with a neoglycoprotein consisting of a chemically modified
      carbohydrate moiety (reductively aminated 3'-sialyllactose) linked to human serum
      albumin. By this procedure an antibody response to the normally non-immunogenic
      carbohydrate structure was obtained. Hybridomas were established, and monoclonal
      antibodies were selected in ELISA based on their binding to the saccharide
      hapten, or to a lactosylceramide-mimicking neoglycolipid, lactose-bis-sulfone.
      One of the selected antibodies, 2H4, was of particular interest, since it also
      bound to glycolipids present on melanoma cells. FACS analysis of a panel of 14
      melanoma cell lines showed that the 2H4 antibody bound to the majority of these.
      In frozen, non-fixed sections or paraffin sections of biopsies the monoclonal
      antibody 2H4 stained melanoma cells, but not tumour infiltrating lymphocytes or
      normal skin. Detailed immunochemical analysis of 2H4, using thin layer
      chromatography revealed that it recognized an internal lactose epitope in several
      glycosphingolipids.

PMID- 7507747
TI  - [Modern treatment of tubal pregnancy].

PMID- 7507748
TI  - Benign proliferative lesions and in situ carcinoma of the breast: new
      immunohistological findings and their biological implications.

PMID- 7507749
TI  - The MCF10 family of spontaneously immortalized human breast epithelial cell
      lines: models of neoplastic progression.

PMID- 7507750
TI  - Sequence-specific 1H-NMR assignments and folding topology of human CD59.
AB  - CD59 is a recently discovered cell-surface glycoprotein that restricts lysis by
      homologous complement and has limited sequence similarity to snake venom
      neurotoxins. This paper describes the first results of a two-dimensional NMR
      study of CD59 prepared from human urine. Nearly complete 1H-NMR assignments were
      obtained for the 77 amino acid residues and partial assignments for the N-glycan
      and the glycosylphosphatidylinositol (GPI) anchor. These results together confirm
      that the C-terminal residue of the mature protein is Asn 77 and that the urine
      derived form retains the nonlipid part of the GPI anchor. The data further
      indicate that the GPI anchor and possibly the N-glycan are structurally
      inhomogeneous and suggest that the phospholipid present in the intact GPI anchor
      was removed by phosphatidylinositol-specific phospholipase-D. The folding
      topology of the protein was determined from NOE enhancements and slowly
      exchanging backbone amide protons and consists primarily of five extended strands
      (denoted beta 1-beta 5 in sequence order), arranged into separate two-stranded
      (beta 1 and beta 2) and three-stranded (beta 3-beta 5) antiparallel beta-sheets.
      The same folding topology is found in all of the snake venom neurotoxins whose
      structures have been determined. The region between the beta 4 and beta 5 strands
      has helical character, a feature that is not present in the neurotoxins but that
      is seen in the topologically similar wheat germ agglutinin.

PMID- 7507752
TI  - Identification of the amino acids comprising a surface-exposed epitope within the
      nucleotide-binding domain of the Na+,K(+)-ATPase using a random peptide library.
AB  - Monoclonal antibodies that bind native protein can generate considerable
      information about structure/function relationships, but identification of their
      epitopes can be problematic. Previously, monoclonal antibody M8-P1-A3 has been
      shown to bind to the catalytic (alpha) subunit of the Na+,K(+)-ATPase holoenzyme
      and the synthetic peptide sequence 496-HLLVMK*GAPER-506, which includes Lys 501
      (K*), the major site for fluorescein-5'-isothiocyanate labeling of the Na+,K(+)
      ATPase. This sequence region of alpha is proposed to comprise a portion of the
      enzyme's ATP binding domain (Taylor, W. R. & Green, N. W., 1989, Eur. J. Biochem.
      179, 241-248). In this study we have determined M8-P1-A3's ability to recognize
      the alpha-subunit or homologous E1E2-ATPase proteins from different species and
      tissues in order to deduce the antibody's epitope. In addition the bacteriophage
      random peptide or "epitope" library, recently developed by Scott and Smith (1990,
      Science 249, 386-390) and Devlin et al. (Devlin, J. J., Panganiban, L. C., &
      Devlin, P. E., 1990, Science 249, 404-406), has served as a convenient technique
      to confirm the species-specificity mapping data and to determine the exact amino
      acid requirements for antibody binding. The M8-P1-A3 epitope was found to consist
      of the five amino acid 494-PRHLL-498 sequence stretch of alpha, with residues
      PRxLx being critical for antibody recognition.

PMID- 7507753
TI  - Modeling the alpha IIb beta 3 integrin solution conformation.
AB  - The alpha IIb beta 3 platelet integrin is the prototypical member of a widely
      distributed class of transmembrane receptors formed by the noncovalent
      association of alpha and beta subunits. Electron microscopic (EM) images of the
      alpha IIb beta 3 complex show an asymmetric particle with a globular domain from
      which two extended regions protrude to contact the lipid bilayer. Distance
      constraints provided by disulfide bond patterns, epitope mapping, and ligand
      mimetic cross-linking studies rather suggest a somewhat more compact conformation
      for the alpha IIb beta 3 complex. We have studied the shape of detergent
      solubilized alpha IIb beta 3 by employing a low-resolution modeling procedure in
      which each polypeptide has been represented as an array of interconnected,
      nonoverlapping spheres (beads) of various sizes. The number, size, and three
      dimensional relationships among the beads were defined either solely by
      dimensions obtained from published EM images of integrin receptors (EM models, 21
      beads), or solely by interdomain constraints derived from published biochemical
      data (biochemical model, 37 beads). Interestingly, although no EM data were
      employed in its construction, the resulting overall shape of the biochemical
      model was still compatible with the EM data. Both kinds of models were then
      evaluated for their calculated solution properties. The more elongated EM models
      have diffusion and sedimentation coefficients that differ, at best, by +2% and 
      18% from the experimental values, determined, respectively, in octyl glucoside
      and Triton X-100. On the other hand, the parameters calculated for the more
      compact biochemical model showed a more consistent agreement with experimental
      values, differing by -7% (octyl glucoside) to -6% (Triton X-100). Thus, it
      appears that using the biochemical constraints as a starting point has resulted
      in not only a more detailed model of the detergent-solubilized alpha IIb beta 3
      complex, where the relative spatial location of specific domains the size of 5-10
      kDa can be tentatively mapped, but in a model that can also reconcile the
      electron microscopy with the biochemical and the solution data.

PMID- 7507756
TI  - Positive selection of CD34+ hematopoietic progenitor cells for transplantation.

PMID- 7507751
TI  - Thermodynamics of BPTI folding.
AB  - A calorimetric study of the basic pancreatic trypsin inhibitor (BPTI) has been
      performed using the new generation of the adiabatic scanning microcalorimeters,
      operating in an extended temperature range of 5-130 degrees C. Precise
      measurements of the heat capacities of the native and unfolded states of BPTI
      show that the heat capacity change upon unfolding strongly depends on
      temperature; its value is maximal at about 50 degrees C and diminishes as the
      temperature is increased. The temperature dependencies of the enthalpy and
      entropy changes upon BPTI unfolding were found to be similar to those normally
      observed for other small globular proteins. The stability of BPTI has been
      correlated with its structure.

PMID- 7507754
TI  - Human immunodeficiency virus type-1 reverse transcriptase and ribonuclease H as
      substrates of the viral protease.
AB  - A study has been made of the susceptibility of recombinant constructs of reverse
      transcriptase (RT) and ribonuclease H (RNase H) from human immunodeficiency virus
      type 1 (HIV-1) to digestion by the HIV-1 protease. At neutral pH, the protease
      attacks a single peptide bond, Phe440-Tyr441, in one of the protomers of the
      folded, active RT/RNase H (p66/p66) homodimer to give a stable, active
      heterodimer (p66/p51) that is resistant to further hydrolysis (Chattopadhyay, D.,
      et al., 1992, J. Biol. Chem. 267, 14227-14232). The COOH-terminal p15 fragment
      released in the process, however, is rapidly degraded by the protease by cleavage
      at Tyr483-Leu484 and Tyr532-Leu533. In marked contrast to this p15 segment, both
      p66/p51 and a folded RNase H construct are stable to breakdown by the protease at
      neutral pH. It is only at pH values around 4 that these latter proteins appear to
      unfold and, under these conditions, the heterodimer undergoes extensive
      proteolysis. RNase H is also hydrolyzed at low pH, but cleavage takes place
      primarily at Gly436-Ala437 and at Phe440-Tyr441, and only much more slowly at
      residues 483, 494, and 532. This observation can be reconciled by inspection of
      crystallographic models of RNase H, which show that residues 483, 494, and 532
      are relatively inaccessible in comparison to Gly436 and Phe440. Our results fit a
      model in which the p66/p66 homodimer exists in a conformation that mirrors that
      of the heterodimer, but with a p15 segment on one of the protomers that is
      structurally disordered to the extent that all of its potential HIV protease
      cleavage sites are accessible for hydrolysis.

PMID- 7507755
TI  - Development of an in vivo method to identify mutants of phage T4 lysozyme of
      enhanced thermostability.
AB  - An M13 bacteriophage-based in vivo screening system has been developed to
      identify T4 lysozyme mutants of enhanced thermal stability. This system takes
      advantage of easy mutagenesis in an M13 host, the production of functional T4
      lysozyme during M13 growth, and the ability to detect lysozyme activity on agar
      plates. Of several mutagenesis procedures that were tested, the most efficient
      was based on misincorporation by avian myeloma virus reverse transcriptase. This
      one-step mutagenesis and screening system has been used to find 18 random single
      site mutant lysozymes, of which 11 were heat resistant. Each of these had a
      melting temperature within 0.8-1.4 degrees C of wild type, suggesting that the
      screening system is quite sensitive.

PMID- 7507757
TI  - CD34 antigen: molecular features and potential clinical applications.
AB  - Despite the wide variety of functions exhibited by mature peripheral blood cells,
      all are derived from a small pool (1-3%) of primitive precursor cells in the bone
      marrow (BM) that bear a unique surface glycoprotein, CD34. Isolated CD34+ cells
      are capable of reconstituting all hematopoietic lineages, both in experimental
      animals and in humans following intensive therapy. CD34+ cells capable of
      reconstituting hematopoiesis are also found at low frequency in peripheral blood
      (PB), a frequency which can be dramatically increased by combinations of
      chemotherapy and recombinant cytokines. In some cases, PB "stem cells" (PBSC) can
      be used to augment or even replace conventional BM autografts. The availability
      of CD34 antibodies has greatly aided the development of techniques for the
      enrichment of primitive progenitor cells, thus allowing studies of the
      hematopoietic potential of stem cells in vitro. Additionally, the use of CD34
      antibodies for the "positive selection" of hematopoietic stem/progenitor cells
      from tumor-contaminated marrow may possibly represent an alternative "purging"
      strategy prior to transplantation. The availability of pure populations of the
      most primitive hematopoietic progenitor cells will also facilitate study of
      genetic manipulation as a practical therapeutic modality.

PMID- 7507758
TI  - The role of stem cell factor in mobilization of peripheral blood progenitor
      cells: synergy with G-CSF.
AB  - The use of cytokine mobilized peripheral blood progenitor cells (PBPC) in
      transplantation following chemotherapy has led to enhanced engraftment.
      Granulocyte-colony stimulating factor (G-CSF) has been shown in a number of
      clinical studies to be an effective mobilizer of PBPC. Preclinical data in mice
      and primates have demonstrated a potential role for the use of stem cell factor
      (SCF) in mobilization of PBPC. In the studies presented here, low doses of SCF
      are shown to synergize with optimal doses of G-CSF to enhance the number and
      quality of PBPC compared to G-CSF alone. Phase I studies using r-metHuSCF
      demonstrated mast cell-related dose limiting effects. The data presented here
      have led to Phase I/II studies to evaluate the potential use of low doses of SCF
      in combination with G-CSF for mobilization of PBPC.

PMID- 7507759
TI  - Oligodeoxynucleotide-based therapeutics for human leukemias.
AB  - As the cell and molecular biology of hematopoietic cell development becomes known
      in greater detail, the roles of individual genes in regulating cell proliferation
      and growth also become better appreciated. Some genes appear to be of particular
      importance in these complex processes and are therefore potential targets for
      molecularly based therapeutics. The rationale for such treatment is that, if the
      function of critical genes can be efficiently and specifically perturbed, then
      the ensuing disruption might lead to preferential leukemic cell death. Several
      technologies for carrying out targeted gene disruption now exist. One approach,
      the "antisense" gene strategy, appears to be particularly well suited to the
      treatment of human leukemia ex vivo and perhaps in vivo as well. Herein I review
      the experience of my laboratory in using this approach to target the c-myb and c
      kit proto-oncogenes in human leukemic cells. Our results suggest that use of
      oligodeoxynucleotides for disrupting the function of specific genes may prove
      useful for both ex vivo and in vivo treatment of patients with hematopoietic
      malignancies.

PMID- 7507760
TI  - [The effect of aprotinin on DNA synthesis in heterokaryon nuclei, obtained upon
      fusion of resting and stimulated NIH 3T3 cells].

PMID- 7507763
TI  - "Stimulation of dihydropyridine-sensitive Ca2+ influx in cultured myoblasts by
      1,25(OH)2-vitamin D3".
AB  - The rapid, non-genomic effects of 1,25(OH)2-vitamin D3 [1,25(OH)2D3] on calcium
      influx in cultured neonate rat and embryonic chick myoblasts were investigated.
      The hormone stimulated 45Ca uptake in a time (1-10 min) and dose (10(-11)-10(-7)
      M)-dependent manner. The effects of 1,25(OH)2D3 on both rat and chick myoblasts
      were mimicked by the Ca(2+)-channel agonist BAY K8644 and effectively suppressed
      by the antagonist nifedipine. 1,25(OH)2D3 induction of Ca2+ uptake was dependent
      on the presence of extracellular calcium, since it was abolished by prior
      addition of EGTA and was restored upon the addition of 1 mM Ca2+ Cell membrane
      depolarization with high K+, similarly to the hormone, elicited a rapid increase
      in Ca2+ uptake (+75% above control). These results suggest the modulation of Ca2+
      influx through competent calcium channels in rat and chick embryo myoblasts by
      1,25(OH)2D3.

PMID- 7507761
TI  - Vanadate inhibition of hyaluronic acid synthesis in Swiss 3T3 fibroblasts.
AB  - Vanadate (50 microM) increases the incorporation of 3H from D-[1,6-3H]glucosamine
      into hyaluronic acid (HA) in serum stimulated Swiss 3T3 fibroblasts. This
      increase is not a result of increased HA synthesis, but is due to a significant
      increase in the specific activity of the cellular UDP-N-acetyl-glucosamine. When
      the 3H incorporation is corrected for the change in precursor specific activity,
      vanadate is shown to inhibit the synthesis of HA, a result that is confirmed by
      measuring the HA with a competitive binding assay. The inhibition of HA synthesis
      by vanadate is also shown to be dependent on the media used in the experiment,
      with a substantial increase in the inhibition seen when the media contains the pH
      indicator, phenol red. The HA synthetase activity of isolated membranes is not
      inhibited by vanadate at concentrations up to 500 microM.

PMID- 7507762
TI  - Effect of beta-sitosterol on uterine biochemistry: a comparative study with
      estradiol and progesterone.
AB  - Administration of estradiol/progesterone to ovariectomized animals significantly
      increased the uterine weight, RNA, DNA and protein concentrations. Similarly,
      administration of beta-sitosterol alone or in combination with estradiol caused a
      marked increase in the above parameters and the maximum influence was evident
      only after median and high dose treatments. However, administration of
      median/high dose of beta-sitosterol along with progesterone accentuated only the
      RNA and protein concentrations but exerted an inhibitory effect on sitosterol
      induced increment in uterine weight and DNA concentrations.

PMID- 7507764
TI  - Possible involvement of nitric oxide in estrogen-induced uterine edema in the
      immature rat.
AB  - We examined whether nitric oxide mediates estrogen-induced uterine edema in the
      immature rat. Immature Wistar rats (19-21 days) received estradiol-17 beta (E2)
      in a single sc dose of 10 micrograms/animal and 6 h later the animals were
      sacrificed and the changes in uterine wet and dry weights were determined. E2
      treatment caused a 93% increase in uterine wet weight (control, N = 6, 39.88 +/-
      3.2 mg; E2 treated, N = 6, 76.8 +/- 4.9 mg), but not in dry weight, suggesting
      that it induces uterine edema. Pretreatment with L-nitroarginine methyl ester (L
      NAME), a competitive antagonist of nitric oxide synthetase, at doses of 10 and 20
      mg/kg, ip, caused a dose-related reduction (59 and 86%) in the uterine wet weight
      increase induced by E2. Furthermore, L-arginine (300-600 mg/kg, sc), the nitric
      oxide precursor, was able to reverse L-NAME (20 mg/kg)-induced decreases in
      uterine weight by 47 and 62%, respectively. The results suggest that nitric oxide
      is the principal mediator involved in estrogen-induced uterine edema in the
      immature rat.

PMID- 7507765
TI  - D-fenfluramine reduces anxiety induced by simulated public speaking.
AB  - To further explore the role of serotonin (5-HT) in anxiety, 28 healthy volunteers
      received in a double-blind study d-fenfluramine (30 mg, p.o.) or placebo, and
      were submitted to a simulated public speaking test (SPS), consisting of speaking
      in front of a video camera. The SPS induced significant increases in subjective
      anxiety evaluated by the visual analogue mood scale of Norris [MANCOVA,
      F(1.66,39.93) = 8.51, P < 0.001], as well as in systolic blood pressure [F(3,72)
      = 5.70, P = 0.001] and in heart rate [F(3,72) = 3.95, P = 0.012]. The drug
      decreased the anxiety factor [F(1,23) = 5.21, P = 0.032], without significantly
      affecting physical sedation, mental sedation or other feelings and attitudes.
      Also, the physiological measurements were not significantly changed by d
      fenfluramine. Reported evidence shows that d-fenfluramine releases 5-HT from
      nerve endings and blocks 5-HT reuptake, indirectly stimulating postsynaptic 5-HT
      receptors. Therefore, the present results indicate that 5-HT inhibits the neural
      substrate of SPS-induced anxiety.

PMID- 7507766
TI  - Comparative study of CD34-positive cells and subpopulations in human umbilical
      cord blood and bone marrow.
AB  - The CD34-positive population of bone marrow cells contain not only committed
      myeloid, erythroid, megakaryocytic and lymphoid progenitor cells but also more
      primitive stem cells capable of initiating haemopoiesis in long-term marrow
      culture that are termed long-term culture initiating cells (LTC-IC). Recently,
      different subpopulations of BM CD34+ cells have been defined. Thus the
      CD34+/CD45RO+ fraction contains both BFU-E and LTC-IC whereas CFU-GM are mainly
      CD34+/CD45RA+ and CD34+/CD33+. As human umbilical cord blood (UBC) also contains
      CD34+ cells and has been used as a source of material for clinical
      transplantation, we have undertaken a comparative study of the expression of
      CD34RO, CD45RA, CD33 and CD38 on CD34+ cells from UCB and BM using directly
      conjugated antibodies and flow cytometry. The frequency of CD34 cells in UCB
      (mean 1.0% +/- 0.3%) was similar to that in harvested pelvic BM (0.8% +/- 0.4%).
      The frequencies of CD34+ cells co-expressing CD33 (UBC: 54.1% +/- 28.7%; BM:
      52.9% +/- 18.5%) and CD45RA (UBC: 24.8% +/- 16.6%; BM: 21.1% +/- 19.7%) were not
      significantly different between UCB and BM. In contrast, a significantly higher
      percentage of UCB-CD34+ cells co-expressed CD45RO+ (19.7% +/- 10.3%) compared
      with BM-CD34+ cells (7.2% +/- 5.3%; p < 0.001). The absolute number of CD34+
      cells in UCB correlated with the number of committed myeloid (CFU-GM) and
      erythroid (BFUe) progenitors; a similar relationship was found for the absolute
      number of CD34+/CD33+ cells. However, the numbers of CD34+/CD45RO+ cells showed
      no correlation with numbers of committed progenitors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7507767
TI  - Durable complete remission in a patient with refractory mediastinal non
      seminomatous germ cell tumor after tandem high-dose chemotherapy and autologous
      bone marrow transplantation.
AB  - The prognosis of patients with relapsed or refractory mediastinal germ cell
      tumors is uniformly poor. There have been no reports of long-term disease-free
      survivors using any currently available salvage regimen. We describe a patient
      with primary mediastinal non-seminomatous germ cell tumor refractory to initial
      and salvage chemotherapy, who entered his first complete remission after surgical
      resection and tandem autologous bone marrow transplantation. The patient remains
      without evidence of disease 19 months after the first BMT.

PMID- 7507768
TI  - Peptidergic nerves in the ureter.
AB  - Vasoactive intestinal peptide (VIP) and substance P were demonstrated in the pig
      ureter by immunohistochemical techniques. Nerves containing these materials were
      related mainly to the smooth muscle layer in the normal and obstructed ureter. In
      isolated ureteral segments, VIP caused relaxation at doses exceeding 0.18
      micrograms/ml, with no significant difference seen in the effect on normal and
      obstructed ureter. Vasoactive intestinal polypeptide may play a role in the
      regulation of ureteral smooth muscle tone.

PMID- 7507770
TI  - Drug resistance in initial isolates of Mycobacterium tuberculosis in England and
      Wales, 1982-1991.
AB  - A total of 1833 out of over 16,000 'initial' isolates of Mycobacterium
      tuberculosis, submitted by hospital laboratories to the PHLS Regional
      Tuberculosis Centres in England and Wales between 1982 and 1991, were resistant
      to one or more first line anti-tuberculosis drugs. Isoniazid resistance was found
      in 6.1% of these strains, half of which were resistant to isoniazid alone.
      Resistance to isoniazid and rifampicin, with or without resistance to other
      drugs, was found in 0.6% of isolates. The proportion of initial isolates
      resistant to one or more drugs was 9.8%. It ranged from 8.0% to 10.9% between
      1982 and 1990, and increased to 14.2% in 1991. The incidence of multiple drug
      resistance remained very low throughout the period. However, in the light of the
      problems with tuberculosis and drug resistance emerging elsewhere in the world,
      vigilance is essential, and enhanced surveillance is being planned in England and
      Wales.

PMID- 7507771
TI  - An outbreak of infection with Salmonella enteritidis phage type 4 associated with
      the use of raw shell eggs.
AB  - A community outbreak of Salmonella enteritidis phage type (PT) 4 infection,
      associated with eating food from a sandwich bar in Colchester, occurred in July
      1991. One hundred and forty-four people were reported with food poisoning, of
      whom 132 met the clinical case definition. Three cohort studies of 92 people
      showed that illness was associated with the consumption of food containing
      mayonnaise. S. enteritidis PT4, indistinguishable by plasmid profile analysis,
      was isolated from stool samples from 83 people, food items including egg shells
      from the sandwich bar, and birds taken from the egg producing farm which supplied
      the eggs. This was the largest recorded outbreak of S. enteritidis PT4 infection
      in recent years associated with eggs produced in the United Kingdom. Existing
      advice on avoiding the use of raw eggs in uncooked dishes had not been followed.
      This outbreak highlights the importance of training in the implementation of this
      advice.

PMID- 7507773
TI  - Influenza activity in England and Wales.

PMID- 7507769
TI  - Multiple B-cell epitopes in a recombinant GRA2 secreted antigen of Toxoplasma
      gondii.
AB  - Two cDNA clones encoding the GRA2 (G.P.28.5) secreted antigen of Toxoplasma
      gondii were expressed in Escherichia coli as glutathione-S-transferase fusion
      polypeptides. A high level of expression was obtained for the first clone
      expressing the 59C-terminal amino acids of GRA2. The other one was an open
      reading-frame of 212 amino acids containing the entire GRA2 cDNA. By ELISA, IgG
      antibodies directed against the 59aa recombinant polypeptide were detected in
      33/44 (75%) sera from patients chronically infected with T. gondii and in 19/23
      (82.6%) sera derived from patients with acute, primary toxoplasmosis. 10 of the
      11 "chronic" sera which were negative by the 59aa ELISA were tested in a
      immunoblot against the 212aa open-reading-frame of GRA2: 8/10 were positive. A
      peptide representing the 15 C-terminal amino acids of GRA2 has been shown to
      contain the epitope recognized by a mouse monoclonal antibody (TG17-179). The
      reactivity of human sera with the 59aa recombinant polypeptide was inhibited to
      varying degrees when the sera were co-incubated with this peptide. Twelve chronic
      sera showed a range of inhibition from 8 to 100% and twelve acute sera an
      inhibition range of 15 to 90%. This suggests that the 15aa C-terminal peptide
      contains an epitope recognized in both the acute and chronic phases of infection
      and that other major epitope(s) exist in the 59aa C-terminal region of GRA2. As a
      conclusion, the recombinant GRA2 protein appears to contain at least three B-cell
      epitopes.

PMID- 7507772
TI  - Influenza surveillance, England and Wales: October 1992-June 1993.

PMID- 7507774
TI  - Selective inhibition of basal but not agonist-stimulated activity of nitric oxide
      in rat aorta by NG-monomethyl-L-arginine.
AB  - 1. Two inhibitors of nitric oxide synthase, NG-monomethyl-L-arginine (L-NMMA, 1
      100 microM) and NG-nitro-L-arginine (L-NOARG, 3-300 microM), each produced a
      concentration-dependent augmentation of phenylephrine-induced tone in endothelium
      containing but not endothelium-denuded rings of rat aorta. Pretreatment with L
      arginine (10 mM) prevented the augmentation of tone induced by L-NOARG and L
      NMMA. 2. Following induction of sub-maximal tone with phenylephrine in
      endothelium-containing rings, acetylcholine (1 nM-3 microM) induced relaxations
      which were inhibited in a concentration-dependent manner by L-NOARG (10-100
      microM). 3. In contrast to the action of L-NOARG, L-NMMA (100-1000 microM) had no
      effect on acetylcholine-induced relaxations. L-NMMA (100-300 microM) also had no
      effect on the endothelium-dependent relaxant actions of ATP (0.1-100 microM),
      whereas L-NOARG (100 microM) produced powerful blockade. 4. Unexpectedly,
      pretreatment with L-NMMA (30-300 microM), as with the endogenous substrate L
      arginine (10 microM-10 mM), inhibited in a concentration-dependent manner the
      ability of L-NOARG (30 microM) to block acetylcholine-induced relaxation. 5. The
      ability of L-NOARG to augment phenylephrine-induced tone and inhibit relaxation
      by acetylcholine and ATP in endothelium-containing rings is consistent with
      blockade of basal and agonist-stimulated production of nitric oxide,
      respectively. 6. The ability of L-NMMA to augment phenylephrine-induced tone
      without affecting relaxation to acetylcholine or ATP in endothelium-containing
      rings suggests a selective ability to block basal but not agonist-stimulated
      production of nitric oxide in rat aorta.

PMID- 7507775
TI  - Effects of ruthenium red and capsazepine on C-fibres in the rabbit iris.
AB  - 1. We have investigated the effects of ruthenium red and capsazepine on a C-fibre
      smooth muscle preparation (the rabbit isolated iris sphincter muscle). 2. Like
      capsaicin, ruthenium red and capsazepine were found to produce contractions in a
      concentration-dependent manner. C-fibre activation was held to be responsible
      since the contractions could be inhibited by tachykinin receptor blockade. 3.
      Both ruthenium red and capsazepine inhibited capsaicin-induced contractions
      concentration-dependently; the pIC50 values were 5.1 and 4.9, respectively. The
      contractions induced by bradykinin, which, like capsaicin, acts by releasing
      tachykinins from C-fibres, were also inhibited by ruthenium red and capsazepine
      in a concentration-dependent manner; the pIC50 values were 4.1 and 4.6,
      respectively. 4. Electrically evoked, tachykinin-mediated contractions were
      inhibited by ruthenium red and capsazepine in a concentration-dependent manner;
      the pIC50 values were 4.3 and 4.5, respectively. 5. The contractile response to
      neurokinin A (NKA) was inhibited by capsazepine (and by capsaicin), but not by
      ruthenium red, in a concentration-dependent manner; the pIC50 value was 4.3. 6.
      The results suggest that, besides their ability to antagonize capsaicin,
      ruthenium red and capsazepine possess a weak capsaicin-like effect. Conceivably,
      capsazepine interacts with binding sites for capsaicin, acting as a partial
      agonist/antagonist, while ruthenium red interacts with capsaicin-operated cation
      channels. The inhibition of electrically evoked- or bradykinin-induced responses
      by capsazepine and ruthenium red suggests that capsaicin/capsazepine binding
      sites and capsaicin-operated cation channels play a role in the process of
      transmitter release in response not only to capsaicin but also to other C-fibre
      stimuli. In addition, capsazepine (and capsaicin) may affect smooth muscle non
      specifically since the response to NKA was also inhibited by this drug. The fact
      that ruthenium red did not affect the response to NKA provides further evidence
      that ruthenium red acts in a mode different from that ofcapsazepine.

PMID- 7507776
TI  - The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic
      agents to modify 5-HT release in the frontal cortex of freely-moving rats.
AB  - 1. The interaction of yohimbine with anxiolytic and putative anxiolytic agents to
      modify 5-hydroxytryptamine (5-HT) release in the frontal cortex of the freely
      moving rat was assessed using the microdialysis technique. 2. The alpha 2
      adrenoceptor antagonist, yohimbine (5.0 mg kg-1, i.p.) increased maximally the
      extracellular levels of 5-HT in the rat frontal cortex by approximately 230% of
      the basal levels. 3. The alpha 2-adrenoceptor agonist, clonidine (30-100
      micrograms kg-1, i.p.) decreased dose-dependently the extracellular levels of 5
      HT in the rat frontal cortex by approximately 0-60% of the basal levels. A 5 min
      pretreatment with clonidine (50 micrograms kg-1, i.p.) prevented the yohimbine
      induced increase in the extracellular 5-HT levels. 4. The benzodiazepine receptor
      agonist, diazepam (2.5 mg kg-1, i.p.) and the 5-HT3 receptor antagonist,
      ondansetron (100 micrograms kg-1, i.p.) (5 min pretreatment) completely prevented
      the yohimbine (5.0 mg kg-1, i.p.)-induced increases in the extracellular levels
      of 5-HT. The 5-HT1A receptor agonist, 8-OH-DPAT (0.32 mg kg-1, s.c.) partially
      antagonized the yohimbine response. 5. A 5 min pretreatment with the 5-HT3/5-HT4
      receptor ligand R(+)-zacopride (10 micrograms kg-1, i.p.) reversed the yohimbine
      (5.0 mg kg-1, i.p.)-induced increase in the extracellular levels of 5-HT to
      approximately 30% below the basal levels. A 5 min pretreatment with S(-)
      zacopride (100 micrograms kg-1, i.p.) failed to modify the response to yohimbine.
      6. The present study provides evidence of the ability of the anxiogenic agent,
      yohimbine, to increase the activity of the central 5-hydroxytryptaminergic system
      and the ability of clonidine and various anxiolytic and putative anxiolytic
      agents to prevent the yohimbine response.

PMID- 7507778
TI  - The induction of nitric oxide synthase and intestinal vascular permeability by
      endotoxin in the rat.
AB  - 1. The effect of endotoxin (E. coli lipopolysaccharide) on the induction of
      nitric oxide synthase (NOS) and the changes in vascular permeability in the colon
      and jejunum over a 5 h period have been investigated in the rat. 2. Under resting
      conditions, a calcium-dependent constitutive NOS, determined by the conversion of
      radiolabelled L-arginine to citrulline, was detected in homogenates of both
      colonic and jejunal tissue. 3. Administration of endotoxin (3 mg kg-1, i.v.) led,
      after a 2 h lag period, to the appearance of calcium-independent NOS activity in
      the colon and jejunum ex vivo, characteristic of the inducible NOS enzyme. 4.
      Administration of endotoxin led to an increase in colonic and jejunal vascular
      permeability after a lag period of 3 h, determined by the leakage of
      radiolabelled albumin. 5. Pretreatment with dexamethasone (1 mg kg-1 s.c., 2 h
      prior to challenge) inhibited both the induction of NOS and the vascular leakage
      induced by endotoxin. 6. Administration of the NO synthase inhibitor NG
      monomethyl-L-arginine (12.5-50 mg kg-1, s.c.) 3 h after endotoxin injection, dose
      dependently reduced the subsequent increase in vascular permeability in jejunum
      and colon, an effect reversed by L-arginine (300 mg kg-1, s.c.). 7. These
      findings suggest that induction of NOS is associated with the vascular injury
      induced by endotoxin in the rat colon and jejunum.

PMID- 7507777
TI  - Depression of primary afferent-evoked responses by GR71251 in the isolated spinal
      cord of the neonatal rat.
AB  - 1. The pharmacological profile of GR71251, a new tachykinin receptor antagonist,
      and its effect on the responses evoked by stimulation of primary afferent fibres
      were studied in isolated spinal cord preparations of neonatal rats. Potential
      changes were recorded extracellularly from a lumbar ventral root (L3-L5). 2. Bath
      application of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) at
      0.01-3 microM to the spinal cord induced depolarization of the ventral root in
      normal artificial cerebrospinal fluid (CSF). The NK1 agonist, acetyl-Arg6
      septide, and the NK3 agonist, senktide, at 0.01-3 microM, also had potent
      depolarizing actions whereas two NK2 agonists, beta-Ala8NKA4-10 and Nle10NKA4-10,
      showed little depolarizing effects at 1 microM. 3. GR71251 (0.3-3 microM) caused
      a rightward shift of the concentration-response curves for SP, acetyl-Arg6
      septide and NKA with pA2 values of 6.14, 6.75 or 6.70, respectively. The effects
      of GR71251 were readily reversible within 15-30 min after its removal. By
      contrast, GR71251 (1-5 microM) had little effect on the depolarizing responses to
      NKB and senktide. 4. GR71251 (1-3 microM) did not depress the depolarizing
      responses to bombesin, neuromedin B and gastrin-releasing peptide in normal
      artificial CSF. 5. Application of capsaicin to the spinal cord induced a
      depolarizing response, which was partially depressed by GR71251 (3-10 microM). 6.
      In the isolated spinal cord preparation, intense electrical stimulation of a
      dorsal root evoked a slow depolarizing response of the contralateral ventral root
      of the same segment. A similar slow ventral root depolarization was evoked by
      electrical stimulation of the ipsilateral saphenous nerve in an isolated spinal
      cord-saphenous nerve preparation. GR71251 (0.3-10 microM) dose-dependently
      depressed these slow ventral root potentials.7. In the spinal cord-peripheral
      nerve preparation, conditioning stimulation of the saphenous nerve evoked an
      inhibition of the muscle nerve-evoked monosynaptic reflex lasting about 20 s. The
      late part of the inhibition was markedly depressed by GR71251 (1-3 microM).8. The
      present results indicate that GR71251 is a potent and specific antagonist for
      tachykinin receptors in the spinal cord. The present study further provides
      evidence for the involvement of SP and NKA in the slow ventral root
      depolarization and the prolonged inhibition of monosynaptic reflex that are
      evoked by primary afferent stimulation.

PMID- 7507779
TI  - Inhibitory actions of diphenyleneiodonium on endothelium-dependent
      vasodilatations in vitro and in vivo.
AB  - 1. This study examined the in vitro and in vivo inhibitory effects of
      diphenyleneiodonium (DPI), a novel inhibitor of nitric oxide (NO) synthase, on
      endothelium-dependent vasodilatations. 2. DPI (3 x 10(-8)-3 x 10(-6) M)
      concentration-dependently inhibited acetylcholine (ACh)-induced relaxation in
      preconstricted rat thoracic aortic rings, with an IC50 of 1.8 x 10(-7) M and a
      maximal inhibition of nearly 100%. DPI (3 x 10(-6) M) also completely inhibited
      the relaxation induced by the calcium ionophore, A23187 but not by sodium
      nitroprusside (SNP). The inhibitory effect of DPI (3 x 10(-7) M) on ACh-induced
      relaxation was prevented by pretreatment with NADPH (5 x 10(-3) M) and FAD (5 x
      10(-4) M) but not L-arginine (L-Arg, 2 x 10(-3) M). Pretreatment with NADPH did
      not alter the inhibitory effect of NG-nitro-L-arginine on ACh-induced relaxation.
      3. The inhibitory effect of DPI on ACh-induced relaxation in the aortae lasted >
      4 h after washout. In contrast to pretreatment, post-treatment (1 h later) with
      NADPH (5 x 10(-3) M) reversed only slightly the inhibitory effect of DPI. 4. In
      conscious rats, DPI (10(-5) mol kg-1) inhibited the depressor response to i.v.
      infused ACh, but not SNP. However, it caused only a transient pressor response
      which was previously shown to be due completely to sympathetic activation. 5.
      Thus, DPI is an efficacious and 'irreversible' inhibitor of endothelium-dependent
      vasodilatation in vivo and in vitro. The mechanism of the inhibition may involve
      antagonism of the effects of FAD and NADPH, co-factors of NO synthase. However,
      unlike the N0-substituted arginine analogues (another class of NO synthase
      inhibitors), DPI-induced suppression of endothelium-dependent vasodilatation in
      vivo does not lead to a sustained rise in blood pressure.

PMID- 7507780
TI  - Relative contributions of direct and indirect mechanisms mediating endothelin
      induced contraction of guinea-pig trachea.
AB  - 1. The present study was undertaken to determine the mechanism of action of
      endothelin-1 (ET-1)-induced contraction of the guinea-pig isolated trachea. 2. ET
      1 (1 nM-0.3 microM) produces a concentration-dependent contraction of guinea-pig
      trachea with an EC50 of approximately 25 nM. The combination of the
      peptidoleukotriene receptor antagonist, SK&F 104353 (10 microM) and the H1
      histamine receptor antagonist, mepyramine (10 microM), which abolishes antigen
      induced contraction in guinea-pig trachea, was without effect on ET-1
      concentration-response curves. Furthermore, the platelet-activating factor (PAF)
      receptor antagonist, WEB 2086, (1 or 10 microM) did not inhibit ET-induced
      contraction. 3. ET-1 (0.3 microM) did not stimulate histamine or immunoreactive
      peptidoleukotriene release from guinea-pig isolated trachea. 4. The release of
      various prostanoids from guinea-pig trachea was increased significantly by ET-1
      (0.3 microM); the profile of release was prostaglandin D2 (PGD2) = PGE2 = 6-keto
      PGF1 alpha (PGI2 metabolite) > thromboxane B2 = PGF2 alpha >> 9 alpha, 11 beta
      PGF2 (PGD2 metabolite). ET-1-induced release of prostaglandins, which was about
      30% of that elicited by antigen in sensitized tissues, was not affected by
      epithelium removal and was observed in tissues from which the smooth muscle had
      been removed. Previous studies in our laboratory indicated that indomethacin
      potentiated contraction produced by high concentrations of ET-1, whereas a
      thromboxane receptor antagonist was without appreciable effect on ET-1
      concentration-response curves. 5. Pretreatment of tissues for 1 h with capsaicin
      (10 microM), which depletes different sensory neurones, produced a small, but
      significant, inhibitory effect on ET-1 concentration-response curves in the
      presence but not the absence of the epithelium. The combination of the NK1
      tachykinin receptor antagonist,CP-96,345 (0.1 microM), and the NK2 tachykinin
      receptor antagonist, SR 48968 (0.1 microM), was without effect on ET-l
      concentration-response curves but substantially antagonized capsaicin-induced
      contraction.6. The present data suggest that in guinea-pig isolated trachea, ET-
      1 produces contraction predominantly via a direct mechanism: there is no
      significant contribution of the release of histamine,leukotrienes, PAF, or
      tachykinins (acting on NK1 or NK2 receptors). Although ET-1 evokes the release of
      an array of prostanoids from the trachea they do not appear to have a major
      influence on the contractile response.

PMID- 7507783
TI  - Utilization of polyclonal serum prostate specific antigen levels in screening for
      prostate cancer: a comparison with corresponding monoclonal values.
AB  - OBJECTIVES: Prostate specific antigen (PSA) measurement has become increasingly
      popular as a screening test for prostatic adenocarcinoma. Although this is a
      sensitive, organ-specific assay, use as a screening tool is hampered by the lack
      of a clearly defined normal range in older men, frequent elevation of PSA levels
      by benign processes, and the availability of two different assays, one polyclonal
      and the other monoclonal, which produce very different values. This study was
      designed to evaluate the distribution of PSA levels by the Yang and corresponding
      Hybritech values in patients from the general population. SUBJECTS AND METHODS: A
      total of 478 volunteers over 40 years of age underwent serum PSA determination by
      the Yang polyclonal radioimmunoassay and digital rectal examination. The PSA
      levels were stratified and the patient distribution analysed. RESULTS: In 69% of
      patients, PSA levels were < or = 2.5 ng/ml (proposed normal range for the Yang
      polyclonal assay). In 89% of patients, PSA levels were < or = 7.3 ng/ml by the
      polyclonal assay which corresponds approximately to the proposed normal range of
      0-4.0 ng/ml by the Hybritech monoclonal assay. Nine per cent of patients fell
      between 7.4 and 18.4 ng/ml by the polyclonal assay (4.1-10 ng/ml by the
      monoclonal assay) and 2% had polyclonal PSA levels > 18.4 ng/ml (> 10 ng/ml by
      the monoclonal assay). Cancer detection rates (influenced by the percentage of
      patients undergoing biopsy) were 0.3% in patients with polyclonal PSA levels < or
      = 2.5 ng/ml, 1.2% in patients < or = 7.3 ng/ml, 20.9% between 7.4 and 18.4 ng/ml,
      and 50% of those > 18.4 ng/ml; the overall cancer detection rate was 3.8%.
      CONCLUSIONS: These data support the use of higher PSA levels as a criterion for
      further evaluation in screening for prostate cancer and establish the frequency
      distribution of PSA in a screening population when the Yang assay is used.

PMID- 7507781
TI  - Aminoguanidine selectively inhibits inducible nitric oxide synthase.
AB  - 1. Endotoxin induces nitric oxide synthase in vascular tissue, including rat main
      pulmonary artery. Currently available agents that cause inhibition of nitric
      oxide synthase are relatively non-selective between the constitutive and
      inducible forms of the enzyme. 2. Aminoguanidine caused a dose-dependent increase
      in phenylephrine-induced tension in intact and endothelium-denuded pulmonary
      artery rings from endotoxin-treated rats, but had no effect on sham-treated
      controls. 3. Contraction caused by aminoguanidine in endothelium-denuded vessels
      from endotoxin-treated rats was unaffected by indomethacin (10 microM), and by
      cimetidine and mepyramine (both 10 microM), excluding an effect of aminoguanidine
      mediated by arachidonic acid metabolites or histamine. 4. Contraction caused by
      aminoguanidine in endothelium-denuded vessels from endotoxin-treated rats was
      abolished by L-arginine (2 mM) and L-NG-monomethyl arginine (300 microM), but
      unaffected by D-arginine and D-NG-monomethyl arginine, suggesting that its action
      is mediated by the L-arginine/nitric oxide pathway. 5. Aminoguanidine had no
      effect on acetylcholine-induced relaxation of intact vessels from shamtreated
      rats. However, relaxation of artery rings from endotoxin-treated rats by L
      arginine was competitively inhibited by aminoguanidine.6. These results in
      isolated main pulmonary arteries of the rat confirm previous reports that
      aminoguanidine is a selective inhibitor of inducible nitric oxide synthase.

PMID- 7507782
TI  - Small cell carcinoma of the urinary bladder. A clinicopathological study of six
      cases.
AB  - OBJECTIVE: To study the clinical, histological, and immunohistochemical findings
      of small cell carcinoma (SCC) of the urinary bladder, and also to delineate its
      behaviour in comparison with transitional cell carcinomas of the bladder.
      MATERIALS AND METHODS: A retrospective review of 552 patients with bladder cancer
      yielded six cases (1%) of small cell carcinoma which were histologically
      identical to pulmonary small cell anaplastic carcinoma. Clinical data and follow
      up were collected. Aside from the conventional histological parameters, an
      immunohistochemical study with AE1-AE3 and Cam 5.2 keratins, epithelial membrane
      antigen, neuron-specific enolase, chromogranin, synaptophysin, ACTH, calcitonin,
      and prostatic specific antigen was performed. RESULTS: The clinical presentation
      did not differ from conventional transitional cell carcinoma, haematuria being
      the most frequent complaint (four cases). All the cases presented as flat
      tumours. On light microscopy, there were oat cell (four cases), intermediate (one
      case) and mixed oat-cell/intermediate (one case) variants. Three cases were
      associated with transitional cell carcinoma. Dysplastic changes were observed in
      the adjacent urothelium in one case only. At the time of diagnosis, all tumours
      were deeply invasive (pT3). Three cases were Stage III and three Stage IV, with
      involvement of regional lymph nodes and metastases to the liver (two cases) and
      lung (one case). Immunohistochemically, epithelial markers were variably
      expressed as AE1-AE3 keratin (5/6), Cam 5.2 keratin (2/6) and epithelial membrane
      antigen (3/6). Neuron specific enolase was demonstrated in every case.
      Chromogranin, however, was expressed in only one case. Synaptophysin, ACTH,
      calcitonin, and prostatic specific antigen all gave negative results. All the
      patients died of the disease and the overall length of survival was very poor
      (range 5-25 months, mean 13.3). CONCLUSION: Small cell carcinomas show the same
      histological patterns as their pulmonary counterpart. Immunohistochemistry
      reveals a wide spectrum of activity, enolase and keratins being the most
      constant. The present study confirms that the overall prognosis of this tumour is
      very poor.

PMID- 7507784
TI  - The effect of transrectal ultrasonography (TRUS) including digital rectal
      examination (DRE) of the prostate on the level of prostate specific antigen
      (PSA).
AB  - OBJECTIVE: To study the effect of transrectal ultrasonography (TRUS) including
      digital rectal examination (DRE) of the prostate on serum prostate specific
      antigen (PSA). PATIENTS AND METHODS: In a diagnostic centre for general
      practitioners serum PSA was determined in patients before, immediately after, and
      one week after TRUS including DRE. In a small group of patients PSA was
      determined at various times after DRE and TRUS. RESULTS: The PSA levels showed a
      statistically significant rise of 20% immediately after DRE and TRUS. After 7
      days the PSA levels had returned to their initial levels. This decrease appeared
      to occur within the first 24 h. CONCLUSION: When applying the diagnostic triad
      PSA, DRE and TRUS blood samples for PSA should preferably be taken before DRE and
      TRUS. If blood samples are taken afterwards, it is safe to do so after seven
      days.

PMID- 7507785
TI  - Carcinoma of the pancreas and periampullary region: palliation versus cure.
AB  - A retrospective study of 310 patients with carcinoma of the head of the pancreas
      or periampullary region was performed. Preoperative bile drainage by placement of
      a stent reduced the number of postoperative complications, especially bleeding (P
      = 0.03). The operative mortality rate was nil in patients with periampullary
      cancer aged under 70 years and 23 per cent in those over 70 years of age (P <
      0.001). In the last 2 years of the study, the mortality rate following resection
      decreased to 2 per cent. Tumour-containing resection margins did not influence
      survival after resection (P = 0.48). Tumour dimension of pancreatic and
      periampullary cancer and the presence of tumour in locoregional lymph nodes (N1a)
      resected with the primary tumour in cancer of the head of the pancreas were of no
      prognostic value. Following palliative resection of carcinoma of the pancreatic
      head, median survival was significantly better than when no resection was
      performed (10.1 versus 3.9 months, P < 0.001). In conclusion, even palliative
      resection may benefit some patients. Preoperative bile drainage is indicated in
      those with jaundice. Resection should be performed, irrespective of tumour size,
      provided that the unit's operative mortality rate is sufficiently low.

PMID- 7507786
TI  - Synaptophysin immunocytochemistry in the regenerating sprouts from the nodes of
      Ranvier in injured rat sciatic nerve.
AB  - Following crush injury of rat sciatic nerve, strong synaptophysin
      immunoreactivity was demonstrated in the regenerating sprouts that emerged from
      the proximal nodes of Ranvier and in their growth cones that extended through the
      space between Schwann cell basal lamina and myelin sheath of the parent axon.
      These findings suggest that synaptophysin is involved in the growth regulation of
      regenerating sprouts.

PMID- 7507787
TI  - Alcohol modulation of cloned GABAA receptor-channel complex expressed in human
      kidney cell lines.
AB  - The effects of n-octanol on GABA-induced currents were examined on the alpha 1
      beta 2 gamma 2s and alpha 1 beta 2 combinations of GABAA receptor subunits
      expressed in a human kidney cell line (HEK 293), using the whole-cell variation
      of the patch clamp technique. The EC50 of the GABA dose-response curve for the
      alpha 1 beta 2 combination was lower than that for the alpha 1 beta 2 gamma 2s
      combination. n-Octanol at 100 microM augmented the GABA-induced currents in a
      dose-dependent manner, decreasing the EC50 of the GABA dose-response curve
      without affecting the maximal response. The magnitude of n-octanol potentiation
      was nearly the same in both combinations. In contrast, a benzodiazepine agonist,
      chlordiazepoxide, augmented the currents of the alpha 1 beta 2 gamma 2s
      combination only. We conclude that the potentiation of GABAA receptor-mediated
      currents by a long carbon chain n-alcohol does not require the gamma 2 subunit.

PMID- 7507788
TI  - Amyloid P component and other acute-phase proteins associated with cerebellar A
      beta-deposits in Alzheimer's disease.
AB  - It is established that amyloid P (AP) component and complement proteins are
      associated with amyloid beta (A beta)-protein deposits in the cerebral cortex of
      Alzheimer's disease (AD) subjects. Here, we used immunocytochemical methods to
      examine the association of these acute-phase proteins with the characteristic
      diffuse plaques of cerebellum in AD. We observed AP and complement C3d, C1q, C5
      and C4bp immunoreactivities in most A beta-protein-reactive plaques of the
      cerebellum. Further, a1-antichymotrypsin immunoreactivity was apparent in at
      least 60% of all the cerebellar diffuse plaques examined. Cerebellar tissue
      bearing the A beta-protein deposits also often exhibited marked angiopathy in the
      pial vessels. We suggest that diffuse plaques of the cerebellum also acquire
      components of the chronic inflammatory response evident in neocortical plaques.

PMID- 7507789
TI  - Electron microscopic evidence that cortical terminals make direct contact onto
      cells of the thalamic reticular nucleus in the monkey.
AB  - Injections of WGA-HRP were made into somatosensory cortex to determine whether or
      not the cortex makes monosynaptic connections with neurons of the thalamic
      reticular nucleus. Two classes of synaptic profiles making asymmetric contacts
      onto small dendrites were labeled. The first class was small, and contained
      densely packed vesicles and few mitochondria. The second, larger class contained
      loosely packed vesicles, several mitochondria, and accounted for approximately
      one-third of labeled contacts.

PMID- 7507790
TI  - Ionotropic and metabotropic components of electrophysiological response of
      cerebellar Purkinje neurons to excitatory amino acids.
AB  - Cerebellar Purkinje neurons possess AMPA ((RS)-alpha-amino-3-hydroxyl-5- methyl-4
      isoxazolepropionic acid)-sensitive ionotropic glutamate receptors (AMPA GluRs)
      and ACPD ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid)-sensitive
      metabotropic glutamate receptors (mGluRs). The contributions of these receptors
      to responses elicited by dual receptor activation in cultured cerebellar Purkinje
      neurons were delineated by quantitative analysis of agonist-induced single unit
      activity. Responses to co-activation using Quis or AMPA + ACPD were biphasic,
      consisting of a dramatic increase in firing rate (excitatory phase) followed by a
      temporary decrease (inhibitory phase). In half of the cells tested bursting was
      induced during both the excitatory and inhibitory phases and the duration of each
      phase was prolonged relative to responses observed in non-bursting cells.
      Quantitative comparisons of these responses and responses produced by selective
      activation of AMPA GluRs and mGluRs revealed that: (a) AMPA GluRs mediated the
      dramatic changes in firing rate, (b) mGluRs mediated the dramatic increases in
      bursting and the extended duration of each phase and (c) these AMPA GluR and
      mGluR mediated effects were largely additive when simultaneously activated.
      Nevertheless, interactions did occur with repeated co-activation of AMPA GluRs
      and mGluRs, as indicated by selective changes in the mGluR-mediated bursting
      component of the response. Such modulation may contribute to synaptic regulation
      of Purkinje neuron excitability, for example, that associated with long term
      depression.

PMID- 7507791
TI  - Enhanced expression of nitric oxide synthase by rat retina following
      pterygopalatine parasympathetic denervation.
AB  - Removal of the pterygopalatine ganglion enhanced the expression of nitric oxide
      synthase (NOS) in the ipsilateral rat retina and optic nerve by
      immunohistochemical and biochemical criteria. The denervation procedure did not
      alter the apparent histochemical reactivity of retinal cells normally
      immunoreactive for NOS but did induce expression in retinal ganglion cells and
      their axons in the retinal nerve fiber layer and optic nerve. After denervation,
      the induced NOS immunohistochemical reactivity was consistently visualized by day
      7, reached a maximum intensity during days 14 to 28, and thereafter gradually
      attenuated to become barely detectable by microscopy at 10 weeks. Biochemical
      assays performed two weeks after pterygopalatine denervation confirmed the
      immunohistochemical observations, especially with regard to the optic nerve. The
      induced enzyme activity in both retina and optic nerve showed calcium dependency.
      These results point towards interactions of the ocular parasympathetic
      innervation and the retina, between which no known neuronal connections exist.

PMID- 7507792
TI  - Age-related changes on monoamine turnover in hippocampus of rats.
AB  - After pargyline treatment the turnover rates of dopamine (DA), noradrenaline
      (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-hydroxytryptamine (5
      HT) and 5-hydroxy-3-indolacetic acid (5-HIAA) has been measured in control and
      aged hippocampus of the rats. In addition, the tyrosine hydroxylase (TH) activity
      and monoamine oxidase-A and monoamine oxidase-B activities have also been
      studied. The TH activity did not change in aged hippocampus as compared to
      controls. The monoamine oxidase-B: monoamine oxidase-A ratio increased in 26
      month-old rats compared with controls. The turnover of DA, DOPAC and NA did not
      show significant changes while 5-HT synthesis, 5-HT accumulation rate and 5-HIAA
      turnover increased in aged rats. Serotonin fibers showed morphological
      dissimilarities between the hippocampus of young and aged rats using
      immunocytochemistry techniques. In aged rats aberrant serotoninergic fibers
      mainly appear in the molecular layer of the dentate gyrus and molecular of the
      hippocampal CA1. It is suggested that the aberrant morphology of 5-HT fibers may
      reflect the local degeneration of serotoninergic hippocampal afferents during
      aging. Increase of 5-HT turnover in aged might be a signal of degeneration.

PMID- 7507793
TI  - Combined choriocarcinoma and yolk sac tumor arising in Barrett's esophagus.
AB  - A patient with primary adenocarcinoma with yolk sac and trophoblastic
      differentiation occurring in Barrett's esophagus is reported. Yolk sac
      differentiation at this site has not been described previously. The diagnosis of
      germ cell differentiation initially was suggested by the finding of elevated
      serum tumor marker levels. The patient experienced disease remission after
      cytotoxic chemotherapy. Germ cell differentiation may be difficult to identify in
      small biopsy samples, which may not be representative of the tumor as a whole.
      The finding of germ cell differentiation defines therapy and predicates for a
      relatively good prognosis, which is contrast to adenocarcinoma. Because of the
      significance of germ cell differentiation in the selection of appropriate
      therapy, immunostaining for germ cell tumor markers is suggested in all patients
      with adenocarcinoma who are younger than 50 years.

PMID- 7507794
TI  - Alpha-fetoprotein-producing gastric carcinoma with enteroblastic differentiation.
AB  - BACKGROUND: Alpha-fetoprotein (AFP) is a useful tumor marker for hepatoma and
      yolk sac tumor. Recently, elevations of serum AFP were reported in patients with
      other malignancies, especially gastric cancers. Two distinct tumor morphologies,
      hepatoid and clear cell, have been correlated with AFP production. METHODS: Two
      patients with AFP-producing gastric carcinoma were evaluated with
      immunohistochemical, ultrastructural, and biochemical studies. RESULTS: In
      Patient 1, the primary and metastatic carcinomas consisted homogeneously of
      tubulopapillary carcinoma with clear cytoplasm. In Patient 2, the cancer was
      composed of three different areas: tubulopapillary carcinoma with clear
      cytoplasm, tumor cartilage, and so-called hepatoid carcinoma. The morphologic
      characteristics of tubulopapillary carcinoma with clear cytoplasm were similar to
      those of the developing gut epithelium at the stage of 2-4 months' gestation. The
      elution patterns of the serum AFP on lectin-affinity sepharose column study also
      suggested a correlation with fetal gut differentiation. CONCLUSIONS: AFP
      producing clear cell gastric carcinomas are differentiated into fetal intestine.
      One patient also had hepatocytic and cartilaginous differentiation, indicative of
      a blastomatous characteristic of the tumor. These tumors arose in association
      with intestinal metaplasia.

PMID- 7507795
TI  - Identification of occult micrometastases in pericolic lymph nodes of Duke's B
      colorectal cancer patients using monoclonal antibodies against cytokeratin and
      CC49. Correlation with long-term survival.
AB  - BACKGROUND: Patients with transmurally invasive, lymph node negative colorectal
      carcinoma (Dukes' B) have a 5-year survival rate ranging from 53.9% to 84.9%. The
      authors postulate that patients with Dukes' B colon cancer who die of their
      disease have occult micrometastases in their pericolic lymph nodes at the time of
      original diagnosis. In an attempt to identify these occult micrometastases,
      pericolic lymph nodes from Dukes' B colon cancer resections were stained
      retrospectively with antibodies against cytokeratin (anti-keratin AE1/AE3,
      Boehringer Mannheim, Indianapolis, IN) and CC49 (a second-generation monoclonal
      antibody directed against TAG-72. METHODS: The authors reviewed all Dukes' B
      (transmurally invasive, lymph node negative) primary colorectal carcinoma
      resection specimens from the surgical pathology files of the Ohio State
      University Hospitals between 1984 and 1987. Survival data were obtained from the
      Tumor Registry of the Arthur G. James Cancer Hospital and Research Institute,
      Columbus, Ohio. The results were analyzed by univariate and multivariate
      analysis. RESULTS: Fifty cases with 568 lymph nodes (11.3 per case) were examined
      with each antibody using standard immunoperoxidase techniques. Positive staining
      for cytokeratin was seen in 14 patients (33 lymph nodes), 6 of whom died of colon
      cancer within 66 months (43%). Only 1 of the 36 patients with cytokeratin
      negative lymph nodes died of colon cancer over the same time period (3%, P =
      0.0009 univariate, P = 0.0013 multivariate). There was no significant difference
      in survival between the CC49-positive and CC49-negative groups. CONCLUSION:
      Immunoperoxidase techniques are capable of identifying micrometastatic disease in
      lymph nodes missed by routine hematoxylin and eosin staining. Further, the
      presence of cytokeratin-positive cells within lymph nodes correlated with a
      significantly poorer prognosis. Therefore, cytokeratin staining of pericolic
      lymph nodes in patients with Dukes' B colorectal cancer is recommended. Larger
      multicenter studies are needed, however, to confirm these results and to evaluate
      the appropriateness of adjuvant chemotherapy in patients whose disease is
      upstaged by immunohistochemical staining.

PMID- 7507796
TI  - Epithelioid hemangioendothelioma with multiple site involvement. Literature
      review and observations.
AB  - This report is a case of epithelioid hemangioendothelioma presenting as multiple
      lytic lesions of the ilium with radiographic findings of diffuse, bilateral lung
      involvement and biopsy-proven scalp involvement. Histologically, the tumor within
      bone and skin exhibited cords and nests of plump, epithelioid-appearing cells
      exhibiting rudimentary vascular differentiation within a myxohyaline stroma.
      Aggressive histologic features were not present. Immunohistochemical reactivity
      for Factor VIII-related antigen, Q-bend 10 (CD34), and cytokeratin were
      demonstrated. Ultrastructural studies revealed abundant intermediate cytoplasmic
      filaments, pinocytotic vacuoles, and Weibel-Palade bodies. The concurrent bone,
      skin, and lung involvement, low-grade histologic type, and female sex of the
      patient aroused speculation about the role of hormones in the development and
      possible treatment of the tumor, but estrogen and progesterone receptors were not
      detected. Despite intense combination chemotherapy, the patient died of widely
      metastatic disease. This report demonstrates the aggressive potential of
      histologically low-grade epithelioid hemangioendothelioma and the need for a
      thorough evaluation for metastases.

PMID- 7507797
TI  - Patterns of differentiation in extraosseous Ewing's sarcoma cells. An in vitro
      study.
AB  - BACKGROUND: In vitro, tissue culture-associated differentiation assays have
      facilitated the identification of multiple tumor-cell types. METHODS: We have
      investigated the capability of differentiation of three extraosseous Ewing's
      sarcoma cell lines toward a neural and muscular direction by in vitro stimulation
      with dibutyryl cyclic adenosine-monophosphate (db cAMP) and 5-azacytidine,
      respectively. RESULTS: Elongation of cytoplasmic processes and increase of neural
      markers chromogranin, S-100 protein, and glial fibrillary acidic protein were
      observed after db cAMP treatment of these lines and neurosecretory granules as
      well as myelin figures were demonstrated ultrastructurally. These results support
      the existence of several pathways of neural differentiation in vitro-
      neuroblastic, Schwannian, and central glial--in stages of maturation more
      advanced than those previously reported in Ewing's sarcoma of bone. The cell
      lines showed no definitive myoblastic differentiation after 5-azacytidine
      treatment. CONCLUSIONS: These data suggest that these three extraosseous Ewing's
      sarcoma cell lines configurate a heterogeneous group of tumors with respect to
      capability of differentiation into the neural lineage, arrested at more advanced
      stages of neural crest development than Ewing's sarcoma of bone and without
      capability of myoblastic differentiation with 5-azacytidine.

PMID- 7507799
TI  - Characteristic clinicopathologic features of adult B-cell lymphoblastic lymphoma
      with special emphasis on differential diagnosis with an atypical form probably of
      blastic lymphocytic lymphoma of intermediate differentiation origin.
AB  - BACKGROUND: Lymphoblastic lymphoma is typically of thymic T-cell phenotype.
      Lymphoblastic lymphoma of B-cell origin (B-lymphoblastic lymphoma) has been
      relatively poorly described. Whether B-lymphoblastic lymphoma should be managed
      like its T-cell counterpart remains to be clarified. METHODS: From 1983 to 1991,
      10 adult patients were diagnosed as having B-lymphoblastic lymphoma at National
      Taiwan University Hospital by using the histomorphologic criteria of
      international working formulation. B-cell phenotype was determined by the
      immunohistochemistry method. Clinicopathologic features of these 10 patients were
      reviewed. RESULTS: Seven patients were grouped as typical type and were
      characterized by an aggressive clinical course with lymph node (7 of 7), bone
      marrow (6 of 7), liver (3 of 7), spleen (3 of 7), and central nervous system (2
      of 7) involvement. The median survival time was 8 months. In contrast, three
      patients had an atypical clinical picture. They were older patients (64-73 years)
      and were characterized by a relatively less aggressive course with predominantly
      bulky nodal involvement. Two of these three patients are alive (31 and 49 months,
      respectively) and well at this report, with one of them being repeatedly
      experiencing disease remission with the use of simple salvage chemotherapeutic
      regimens. Further studies revealed that tumor tissues of these three atypical
      cases had strong expression of CD5 (Leu-1) marker. CONCLUSION: B-lymphoblastic
      lymphoma diagnosed by histomorphologic criteria should be further distinguished
      from a relatively favorable subtype, which probably represents a variant of
      blastic lymphocytic lymphoma of intermediate differentiation as described by
      Lardelli et al. Clinical features of typical B-lymphoblastic lymphoma, except for
      the lack of mediastinal involvement, is similar to its T-cell counterpart.

PMID- 7507798
TI  - Predictors of pathologic stage in prostatic carcinoma. The role of
      neovascularity.
AB  - BACKGROUND: Prostate adenocarcinoma is a significant cause of morbidity and
      mortality in older men. However, the histologic prevalence far exceeds clinically
      manifest disease. Increased screening has resulted in the detection of a large
      number of carcinomas of unknown malignant potential. The authors investigated
      tumor angiogenesis to predict pathologic stage in prostatic tumors. Angiogenesis
      in prostatic intraepithelial neoplasia (PIN), a putative premalignant lesion,
      also was investigated. METHODS: Immunohistochemistry was used to highlight the
      tumor vasculature. Vessels were quantified using computerized image analysis. A
      minimum of five randomly selected microscopic fields were measured from each
      tumor. To investigate PIN, the authors measured vessels per millimeter of gland
      perimeter, compared with benign glands in the same patient. RESULTS: Vessel
      density (vessels per millimeter squared [vv/mm2]) correlated with pathologic
      stage. The mean vessel density of organ-confined tumors was 80.2 vv/mm2 (95%
      confidence interval [CI], 71.4-91.0), compared with 110.4 vv/mm2 (95% CI, 97.9
      122.8) for tumors with capsular penetration or positive lymph nodes. Logistic
      regression analysis and modeling showed vessel density superior to histologic
      grade and preoperative prostate-specific antigen (PSA) level in distinguishing
      organ-confined tumors from those having extracapsular extension or pelvic lymph
      node metastasis. PIN in acini and ductules had increased microvascularity
      relative to benign epithelium in 18 of 25 tumors (P < 0.05). CONCLUSIONS:
      Neovascularity has been demonstrated to be a prerequisite for tumor progression.
      These data demonstrate that microvessel density in prostatic carcinoma is an
      independent predictor of pathologic stage and, presumably, malignant potential.
      Quantification of tumor angiogenesis may allow stratification of patients to type
      of treatment and may allow selection of expectant management for men with low
      tumor microvessel density.

PMID- 7507800
TI  - Role of phosphorylation in keratin and vimentin filament integrity in cultured
      thyroid epithelial cells.
AB  - Cytokeratin and vimentin intermediate filaments (IFs) possess relatively stable
      polymeric properties which can be affected by phosphorylation. The present study,
      using cultures of thyroid epithelial cells, shows by indirect immunofluorescence
      that these cells contain both keratin tonofilament and vimentin IF complexes.
      Immunoblots of Triton X-100 insoluble cytoskeletal fractions show vimentin, and
      approximately 52 kDa type II and 40/38 kDa type I keratins. Under "basal"
      conditions, following prelabeling of cells with [32PO4], vimentin is not
      significantly phosphorylated, while both type II and I keratins are
      phosphorylated. Treatment of cells for 20 min with 1 mM dbcAMP or 0.4 microM 12-O
      tetradecanoyl-phorbol-13-acetate (TPA), to stimulate protein kinase A and C,
      respectively, has no effect on either the phosphorylation state or cytoplasmic
      filament integrity of vimentin. However, while dbcAMP also does not affect
      keratin filaments, TPA increases both type II and I phosphorylation approximately
      3-fold, and concomitantly disrupts tonofilament complexes associated with the
      nucleus, cytoplasm, and desmosomes. TPA-treated cells also show dramatic shape
      changes and protrusive activity. Tryptic peptide mappings show phosphorylations
      of at least 6 and approximately 2 additional sites for type II and I keratins,
      respectively, vs. [32P]-peptides from control cells. Treatment of [32PO4]-labeled
      cells with 0.4 microM calyculin A to inhibit types 1 and 2A phosphatase activity
      causes hyperphosphorylation of both vimentin and keratin, disruption of IF
      complexes, and actomyosin/cell contraction within 20 min. Quantitatively,
      approximately 50% of the type II/I keratin hyperphosphorylations are at some
      sites apparently also phosphorylated after TPA treatment. Thus, in these cells,
      IFs are specifically and differentially affected and regulated by the activity of
      several kinases.

PMID- 7507801
TI  - The nad6 gene and the exon d of nad1 are co-transcribed in wheat mitochondria.
AB  - The exon d of nad1 is located 993 bp upstream of the nad6 gene in the wheat
      mitochondrial genome. Transcription analyses of both sequences (nad1 exon d and
      the nad6 gene) were done by Northern hybridization using RNA from wheat seedlings
      and tissue cultures derived from immature embryos. A complicated pattern was
      generated with a probe including exon d of nad1 and the whole nad6 gene. An 0.71
      kb transcript is specific to nad1 exon d whereas a 1.2-kb transcript is specific
      to the nad6 gene. Three larger transcripts hybridize to both probes suggesting
      that nad1 exon d and nad6 are co-transcribed. This co-transcription has been
      directly demonstrated by cDNA synthesis on mtRNAs and sequencing of the PCR
      amplification product.

PMID- 7507802
TI  - [Hyperamylasemia and pancreatic diseases in children].
AB  - Elevated alpha-amylase activity in serum was thought for a long time to be a
      laboratory standard in diagnosis of acute pancreatic disease. The purpose of this
      study was to evaluate the clinical usefulness of routine measurement of total
      serum amylase (using the Boehringer Mannheim EPS method) and pancreatic
      isoamylase (using Boehringer Mannheim EPS method) and lipase (Kodak Eastman) in
      children. Authors examined the group of 93 children with abdominal pain whose age
      ranged from 5 to 17 years. In previous laboratory measurements using Spofa test
      (Slovakofarma) they were found to have elevated alpha-amylase in serum, thus the
      pancreatic disorder was put in question. A pancreatic disorder was proven in 9
      children (9.7%) from this group. The authors consider the measurements given
      above to be the markers significantly improving the specificity of routine
      biochemistry in children with pancreatic diseases.

PMID- 7507803
TI  - Characterization of CA 125 antigen identified by monoclonal antibodies that
      recognize different epitopes.
AB  - The present study was undertaken to characterize the antigenic determinant of the
      CA 125 macromolecules recognized by newly developed monoclonal antibodies (M 11,
      130-22, 145-9, 602-1, and 602-6), examine their relationship among the epitopes
      recognized by these antibodies, and develop a series of enzyme-linked
      immunosorbent assays (ELISAs) in which various combinations of antibodies are
      used in a double-determinant sandwich mode. The antigenic determinants of CA 125
      were characterized by several methods including competitive ELISA and
      immunoblotting. These antibodies, as well as OC 125, reacted with ovarian cancer
      (HOC-I) cell extract in a dose-dependent manner. Purified CA 125 antigen with a
      molecular mass of less than 200 kDa (CA 125 < 200 kDa) had a significant
      inhibitory effect on the reaction between the cancer cell extract and all these
      antibodies. The reactivity of M 11, 130-22, 145-9, 602-1, and 602-6 to the cancer
      cell extract was not significantly inhibited by purified CA 125 > or = 200 kDa,
      whereas the reactivity of OC 125 was completely inhibited by CA 125 > or = 200
      kDa. The antigenic determinants of M 11, 145-9, 602-6, 130-22, and 602-1 were
      closely related to each other, in this order; whereas OC 125 recognized a
      different epitope on a structurally identical molecule. The use of these
      monoclonal antibodies in combination with each other may result in the
      development of a more specific and sensitive assay for CA 125.

PMID- 7507804
TI  - Comparison of the effect of rapamycin and FK506 on release of prostacyclin and
      endothelin in vitro.
AB  - Alterations in mesangial and endothelial cell production of vasoactive substances
      may be a contributing factor to the decreased renal blood flow and glomerular
      thrombosis associated with FK506 nephrotoxicity. In preliminary studies Rapamycin
      (RAPA) appears to induce fewer renal side-effects than FK506, although further
      documentation is required. In this study, the effects of FK506 and RAPA on
      release of prostacyclin, a vasodilator, and endothelin, a vasoconstrictor, were
      investigated in cultured rabbit mesangial and endothelial cells. In general, the
      effects of both RAPA and FK506 on the basal or stimulated release of prostacyclin
      (as measured by release of its stable metabolite, 6-keto-PGF1 alpha) or
      endothelin from mesangial cells and endothelial cells were similar with the
      following exceptions: RAPA resulted in a significant (p < 0.05) increase in the
      release of prostacyclin (PGI2) from endothelial cells, while in contrast, FK506
      resulted in a significant decrease in the release of this analyte from these
      cells. The similar effects both drugs have on release of vasodilatory and
      vasoconstrictor substances in vitro does not explain the differences in renal
      side-effects of the drugs in vivo.

PMID- 7507805
TI  - High concentrations of immunoreactive gliostatin/platelet-derived endothelial
      cell growth factor in synovial fluid and serum of rheumatoid arthritis.
AB  - Since neovascularization plays an important role in the propagation of rheumatoid
      synovitis, we analyzed the concentration of gliostatin/platelet-derived
      endothelial cell growth factor (GLS/PD-ECGF), a potent angiogenic and chemotactic
      factor, in the synovial fluid and serum of rheumatoid arthritis (RA) patients.
      The immunoreactive GLS/PD-ECGF concentrations (mean value +/- S.D.) in synovial
      fluid, measured by a sandwich enzyme immunoassay, were significantly higher in RA
      patients than in osteoarthritis (OA) patients (233.02 +/- 219.40 vs. 9.09 +/-
      14.86 ng/g, P < 0.001), and the serum concentrations were also higher in RA
      patients than in age-matched controls (8.77 +/- 7.60 vs. 3.74 +/- 2.61 ng/ml, P <
      0.005). These results suggest that GLS/PD-ECGF may participate in the endothelial
      proliferation resulting in initiation of the extensive emigration of mononuclear
      cells and proliferation of the synovial tissues in rheumatoid arthritis, and that
      the immunoreactive GLS/PD-ECGF in serum as well as synovial fluids may be a
      useful diagnostic marker of RA.

PMID- 7507806
TI  - Plasma levels of bactericidal/permeability-increasing protein (BPI) and
      lipopolysaccharide-binding protein (LBP) during hemodialysis.
AB  - Several proteins modify the biological response to lipopolysaccharide (LPS). Both
      bactericidal/permeability-increasing factor (BPI), a protein stored in
      neutrophils, and the acute phase protein LPS-binding protein (LBP) bind to LPS;
      however, BPI inhibits while LBP enhances binding of LPS to leukocytes and
      subsequent induction of cytokines. We investigated plasma levels of BPI, LBP,
      elastase and C5a before, during and after hemodialysis (HD). Six patients were
      dialysed with Cuprophane (Cup) and polysulfone (PS) low-flux dialyzers on two
      consecutive HD sessions. There was a significant, 10.9 +/- 2.8-fold increase in
      BPI after 4-hour HD compared to predialysis and a 4.4 +/- 1.6-fold increase in
      elastase after 4-hour HD using Cup. Plasma levels of BPI and elastase decreased
      rapidly after the dialysis session. HD with PS resulted in a smaller, but still
      significant rise in BPI (3.7 +/- 1.6-fold at 4 hours) and elastase (1.69 +/- 0.2
      fold at 4 hours). Levels for BPI and elastase were similar in the arterial and
      venous blood lines of the dialyzer. Plasma levels of LBP did not change during or
      after the HD session. These data indicate that BPI, but not LBP is released
      during HD with Cup and to a lesser extent with PS. Activation of neutrophils and
      release of BPI during HD may influence the biological response to bacterial
      products possibly introduced during HD.

PMID- 7507807
TI  - Reliability of immunoassays for anti-HCV antibodies (ELISA and RIBA II) in
      patients with essential mixed cryoglobulinemia (EMC).
AB  - The recent reports of a very high frequency of signs of hepatitis C virus (HCV)
      infection among patients with essential mixed cryoglobulins (EMC) suggest new
      hypotheses for the pathogenesis of this disease. However, most of these studies
      have been seriously criticized. The serologic test designed for detection of anti
      HCV antibodies (ELISA, RIBA I and II) may yield a significant rate of false
      positive results when performed on cryoglobulinemic sera, and the detection of
      the HCV genome by PCR is still heavily conditioned by practical problems.
      Indirect, but possibly more reliable, evidence of HCV infection in
      cryoglobulinemic patients might come from the demonstration of anti-HCV
      antibodies by a conventional technique (ELISA or RIBA) in the purified polyclonal
      non-rheumatoid immunoglobulinemic fraction excreted in the urine by glomerular
      filtration. Fifty-two patients whose serum had tested positive for HCV antibodies
      (by ELISA and RIBA) on multiple occasions were enrolled in this study. They were
      diagnosed as having either EMC or HCV chronic hepatitis without cryoglobulinemia
      at least one year ago. The urine samples of these patients were tested for anti
      HCV antibodies by ELISA and RIBA. In patients with chronic C hepatitis the
      antibodies most frequently found in the serum were anti-C33c and anti-C22-3. The
      results of the RIBA were substantially confirmed by ELISA, with a positive test
      in the urine of 30 of 32 seropositive patients. Similar results were obtained in
      patients with EMC II. We conclude that the specificity of the RIBA and ELISA
      tests for HCV antibodies in patients with EMC appears to be as high as in HCV+
      patients without serum cryoglobulins. EMC patients have a high incidence of HCV
      infection and active chronic liver disease.

PMID- 7507808
TI  - [Distribution of nitric oxide synthase activity in rat brain--analysis by high
      performance liquid chromatography].
AB  - As a basic study to investigate the involvement of nitric oxide in the
      pathogenesis of central nervous system diseases, we have established an assay
      system to measure nitric oxide synthase (NOS) activity by a high performance
      liquid chromatography monitoring conversion of arginine into citrulline. NOS
      activity in the rat brain was calcium-dependent and inhibited by L-nitro
      arginine, a specific NOS inhibitor. The activities in the discrete brain regions
      were in the order cerebellum > olfactory bulb > striatum > hippocampus > cerebral
      cortex > midbrain > hypothalamus > pons.

PMID- 7507809
TI  - In situ Ca(2+)-induced Ca2+ release from a ryanodine-sensitive intracellular Ca2+
      store in corneal epithelial cells.
AB  - 1. In a number of tissues, Ca2+ signaling involves Ca(2+)-induced Ca2+ release
      (CICR) from ryanodine- and caffeine-sensitive intracellular Ca2+ stores. We
      sought evidence for such a mechanism in bovine corneal epithelial cells (BCE). 2.
      We have identified a microsomal fraction of BCE which possesses high-affinity
      [3H]-ryanodine binding sites indicating the presence of the ryanodine receptor
      Ca2+ channel. 3. Functional evidence for CICR is that in fura-2 loaded BCE the
      magnitude of Ca2+ transients induced by the addition of either the adenylate
      cyclase activator, forskolin, or the L-type Ca2+ channel agonist, BAY-K 8644,
      were both enhanced by preincubation with 5 microM ryanodine. This ryanodine
      enhancement provides evidence that Ca2+ release from a ryanodine-sensitive
      intracellular Ca2+ store also contributes to the Ca2+ transients. Therefore,
      Ca(2+)-induced Ca2+ release is a component of Ca2+ signaling in BCE.

PMID- 7507810
TI  - Expression of a P0-like glycoprotein in central nervous system myelin of
      amphibians (Ambystoma mexicanus, Xenopus laevis and Rana catesbeiana).
AB  - 1. The myelin protein profiles in the CNS and PNS of three species of amphibians
      were analyzed by biochemical and immunohistochemical methods. 2. The CNS myelin
      of the African clawed frog (Xenopus) and the Mexican salamander (axolotl)
      contained, in addition to proteolipid protein, a unique protein zero (P0)-like
      protein, whereas the adult bullfrog did not. 3. A strong expression of the P0
      like protein in the bullfrog CNS myelin was found transiently at ontogenetically
      early phases including at the time of metamorphosis. 4. The CNS P0-like protein
      and the PNS P0 protein showed a difference in reactivity with lectins and anti
      L2/HNK-1 antibodies, suggesting that the two proteins differ in some aspects of
      their carbohydrate structures.

PMID- 7507811
TI  - Galanin: a candidate neurotransmitter in the porcine gastrointestinal tract.

PMID- 7507812
TI  - Mx proteins: GTPases involved in the interferon-induced antiviral state.
AB  - Mx proteins have molecular masses between 70 and 80 kDa and their synthesis is
      tightly regulated by interferons in mammalian and non-mammalian vertebrates. Some
      Mx proteins function as intracellular mediators of the interferon-induced
      antiviral state. When suitable cDNA constructs were constitutively expressed in
      mouse 3T3 cells the mouse nuclear Mx1 protein conferred selective resistance to
      influenza virus. The human cytoplasmic MxA protein conferred resistance to
      influenza virus and vesicular stomatitis virus but not to other viruses. Mx1
      blocks influenza virus mRNA synthesis within the nucleus of infected cells. Mx1
      presumably interacts with the influenza virus polymerase subunit PB2, because
      overexpression of PB2 titrates out the Mx1 block. MxA does not inhibit mRNA
      synthesis of influenza virus; it inhibits a subsequent cytoplasmic viral
      multiplication step. A possible target is the transport of newly synthesized
      influenza virus polymerase proteins back to the nucleus. Inhibition by MxA of
      vesicular stomatitis virus, which replicates in the cytoplasm, is at the
      transcriptional level. Parts of the N-terminal halves of all known Mx proteins
      are highly conserved. They contain the typical GTP-binding motif and show
      significant homology to other members of a new family of GTPases that includes
      rat dynamin, Drosophila Shibire and the yeast proteins Vps1/Spo15 and Mgm1.
      Purified Mx1 and MxA proteins possess GTPase activity. The GTP/GDP conversion
      rates are about 40 per min, and Km values about 700 microM. Mx1 and MxA variants
      with mutations in the GTP-binding sequences that violate the consensus are unable
      to confer virus resistance in vivo or to hydrolyse GTP in vitro, suggesting that
      GTPase activity is necessary for antiviral activity of Mx proteins. We
      hypothesize that the antivirally active Mx proteins (directly or indirectly) bind
      to polymerase proteins of susceptible viruses, thereby abolishing normal viral
      polymerase function. Interaction of Mx with viral targets is probably a GTP
      dependent process.

PMID- 7507813
TI  - Role of anterior retinal cryoablation in the management of neovascular glaucoma.
AB  - In a prospective study, the effect of anterior retinal cryoablation (ARC) in the
      management of neovascular glaucoma (NVG) was evaluated over two years, in 72
      patients (74 eyes). The outcome of trabeculectomy/seton surgery preceded by 360
      degrees ARC was also analysed in 12 eyes of 12 patients (6 eyes in each group).
      Following ARC, pain relief with dramatic regression of anterior chamber
      inflammatory reaction was observed in 95% of the patients (59 eyes). At the end
      of the follow up, as confirmed by iris fluorescein angiography, regression of
      neovascularization of the iris was documented in 93.5% (58 eyes) of the cases.
      Intraocular pressure control (< or = 22 mm Hg) was achieved in 82.3% (51 eyes)
      cases. IOP control of < or = 22 mm Hg was achieved in all the 6 eyes with the
      seton surgery following ARC. Similarly, control of IOP was successfully achieved
      in all the 6 eyes of patients with NVG with trabeculectomy with post operative
      course of 5-fluorouracil following ARC. ARC is strongly recommended in NVG,
      especially in eyes with media opacities and as a preliminary procedure for
      filtering surgery or drainage implant surgery.

PMID- 7507814
TI  - Absorption, metabolism, and excretion of risperidone in humans.
AB  - The absorption, metabolism, and excretion of the novel antipsychotic risperidone
      was studied in three healthy male subjects. One week after a single oral dose of
      1 mg [14C]risperidone, 70% of the administered radioactivity was recovered in the
      urine and 14% in the feces. Unchanged risperidone was mainly excreted in the
      urine and accounted for 30, 11, and 4% of the administered dose in the poor,
      intermediate, and extensive metabolizer of debrisoquine, respectively. Alicyclic
      hydroxylation at the 9-position of the tetrahydro-4H-pyrido[1,2-a]-pyrimidin-4
      one moiety was the main metabolic pathway. The active metabolite 9-hydroxy
      risperidone accounted for 8, 22, and 32% of the administered dose in the urine of
      the poor, intermediate, and extensive metabolizer, respectively. Oxidative N
      dealkylation at the piperidine nitrogen, whether or not in combination with the 9
      hydroxylation, accounted for 10-13% of the dose. In methanolic extracts of feces,
      risperidone, and benzisoxazole-opened risperidone and hydroxylated metabolites
      were detected. 9-Hydroxy-risperidone was by far the main plasma metabolite. The
      sum of risperidone and 9-hydroxy-risperidone accounted for the largest part of
      the plasma radioactivity in the three subjects. Although the debrisoquine-type
      genetic polymorphism plays a distinct role in the metabolism of risperidone, the
      pharmacokinetics of the active fraction (i.e. risperidone plus 9-hydroxy
      risperidone) remained similar among the three subjects.

PMID- 7507815
TI  - Isolation, identification, and biological activities of oxidative metabolites of
      FK506, a potent immunosuppressive macrolide lactone.
AB  - To characterize structures and biological activities of FK506 metabolites, FK506
      was incubated with liver microsomes prepared from phenobarbital-treated rats in
      the presence of NADPH generating system under aerobic condition. Oxidative
      metabolites formed in the reaction medium were isolated and identified. Purified
      samples were analyzed by HPLC, mass spectrometry, and NMR spectroscopy. M-I, M
      II, and M-III were the O-demethylated metabolites at the 13-, 31-, and 15
      positions of FK506, respectively, and M-IV was the monohydroxylated metabolite at
      the 12-position. M-I was the dominant metabolite in this reaction system. M-II
      and M-III retained the tetrahydropyrane ring in their structures like FK506, but
      M-I and M-IV had rearranged structures in which the tetrahydropyrane ring was
      changed to a tetrahydrofuran ring. Measuring the immunosuppressive activity in
      the mouse mixed lymphocyte reaction system, IC50 values for M-I, M-II, M-III, M
      IV, and FK506 were 1.65, 0.23, > 127, 5.52, and 0.15 nM, respectively. Reactivity
      of the metabolites with mouse anti-FK506 monoclonal antibody was studied and
      immunocross-reactivity of M-I, M-II, M-III, and M-IV with the antibody were nil,
      109.0, 90.5, and 8.8% of FK506, respectively. These results indicate that rat
      hepatic microsomes oxidatively metabolize FK506 to four metabolites, and some of
      them exhibit pharmacological activity.

PMID- 7507817
TI  - Monitoring the response of microcontaminants by dynamic Daphnia magna and
      Leuciscus idus assays in the Rhine Delta: biological early warning as a useful
      supplement.
AB  - Following some severe upstream calamities in the eighties, biological early
      warning systems with fish and waterfleas were installed at monitoring stations in
      the Rhine and the Meuse. Laboratory tests suggest that these whole-organism
      monitors are likely to respond at concentrations close to lethal levels. Current
      average and peak concentrations of compounds that can be identified and of which
      information on toxicity is available are often below these levels. Nevertheless,
      several alerts were registered in recent years. This may be attributed to the
      combined effect of known and unknown compounds under prevailing field conditions.
      Results are compared to experiences at other locations and some prospects on
      development in the future are given.

PMID- 7507816
TI  - The influence of sediment and colloidal material on the bioavailability of a
      quaternary ammonium surfactant.
AB  - The bioaccumulation and tissue distribution of a quaternary ammonium surfactant
      (hexadecylpyridinium bromide, HPB) in aquatic organisms was assessed under a
      variety of exposure conditions. Tadpoles, clams, and minnows were exposed
      simultaneously to sublethal levels of [3H]HPB under flowthrough conditions for a
      period of 7 days. Four exposure conditions were studied: water-borne HPB alone,
      water-borne HPB flowed over a natural sediment, waterborne HPB mixed in a
      suspension of bentonite clay, and HPB sorbed to a natural sediment. In addition,
      the significance of ingestion as an exposure pathway for HPB was assessed in a
      series of oral-dosing experiments conducted with tadpoles. Gill tissues
      accumulated the highest HPB residues for organisms exposed to the chemical in the
      absence of sediment or clay. The accumulation of HPB in all tissues, but
      especially in gills, was reduced significantly in the presence of sediment or
      clay. This finding is important because gill tissue is a primary site of toxic
      action for quaternary ammonium compounds. Tadpoles ingested HPB-contaminated
      sediment and clay, which became a source of exposure for GI-tract tissues. The
      results of oral-dosing experiments confirmed that sorbed HPB did contribute to
      the accumulation of this compound in intestinal tissues.

PMID- 7507818
TI  - Comparative response of rainbow trout and rat to the liver mitogen, lead.
AB  - Lead nitrate and acetate are potent liver mitogens in the Wistar rat. Prior
      exposure to these agents has been found to alter their susceptibility to
      hepatotoxins. The present study assessed the capacity of both lead compounds to
      cause mitogenicity in the liver of adult male and female rainbow trout. Groups
      treated with a single intravenous or intraperitoneal injection of lead nitrate or
      lead acetate exhibited no statistically significant (P < 0.05) alterations in
      liver/body weight ratio nor hepatic DNA content. Results provide evidence of
      significant interspecies variation in the mitogenic response of rainbow trout and
      Wistar rats to the mitogenic potential of lead in the liver.

PMID- 7507819
TI  - Toxic effects of linear alkylbenzene sulfonate on the tiger prawn, Penaeus
      monodon.
AB  - The toxic effects of linear alkybenzene sulfonate (LAS) on the larvae and
      juveniles of tiger prawn Penaeus monodon were tested. The 24-hr LC50 values of
      LAS were 0.06, 0.10, and 3.11 ppm for the zoea 2nd substage, mysis 2nd substage
      (M2), and postlarva 12th substage (PL12) of the tiger prawn, respectively. The 48
      hr LC50 values of LAS were 0.07, 1.03, and 4.36 ppm for M2, PL12, and postlarva
      15th substage of the tiger prawn, respectively. The hepatopancreatic glutathione
      (GSH) in juvenile tiger prawn was obviously depleted when LAS concentration was
      over 1.0 ppm. The hepatopancreatic GSH content of tiger prawn exposed to
      solutions of greater than 1.0 ppm LAS was difficult to raise to normal levels,
      even after the tiger prawns were switched to an LAS-free solution. The activity
      of malate dehydrogenase in the serum of juvenile tiger prawns exposed to 10.0 ppm
      LAS solution was significantly increased.

PMID- 7507820
TI  - The neuropathology of trimethyltin in the marmoset (Callithrix jacchus)
      hippocampal formation.
AB  - The effects of single and repeated doses of trimethyltin (TMT) treatment on the
      central nervous system (CNS) of the marmoset were investigated. For the acute
      dose experiment adult animals were administered 3 mg/kg of TMT chloride (ip) and
      were then observed for changes in behavior. Within 24 hr postinjection all
      animals developed tremors, ataxia, and unresponsiveness. Half of the animals had
      severe clinical deterioration and died at 2 to 3 days following treatment.
      Surviving marmosets were sacrificed and the brain was subsequently perfusion
      fixed for light microscopic examination. Neuronal degeneration was observed in
      many cells of the Ammon's horn and fascia dentata of the hippocampus. For the
      chronic-dose experiment, adult marmosets received (ip) weekly doses of 0.75 mg/kg
      of TMT chloride for 24 weeks. No evident clinical signs or behavioral changes
      were observed in any of the treated animals. Histological examination revealed
      neuropathological changes comparatively similar but less severe than those
      observed in the acute-treated animals. The differences in toxicity effects
      between acute and chronic TMT administration are compared and discussed.

PMID- 7507821
TI  - Accumulation of polychlorinated terphenyls in aquatic biota of an estuarine
      creek.
AB  - Aroclor 5432, a mixture of polychlorinated terphenyls (PCT), was detected in
      several biological compartments including saltmarsh cordgrass (Spartina
      alterniflora), American oysters (Crassostrea virginica), red-jointed fiddler
      crabs (Uca minax), wharf crabs (Sesarma reticulatum), and mummichogs (Fundulus
      heteroclitus) collected from Tabbs Creek. This tidal creek is located in the
      southern Chesapeake Bay region and contains sediments with high concentrations of
      PCT. Samples were collected at four sites, ranging from a suspected outfall near
      the head of the creek, to its mouth, approximately 2.5 river kilometers
      downstream. Species from several phyla were selected in order to examine PCT
      accumulation in physiologically and ecologically different organisms. PCT
      concentrations in sediment, saltmarsh cordgrass, native oysters, and fiddler
      crabs decreased with distance downstream. Residues in transplanted oysters and
      mummichogs showed a more variable trend with distance downstream. The organism
      with the highest mean concentration (18,300 micrograms/kg dry wt) was the native
      oyster, a benthic filter feeder.

PMID- 7507822
TI  - Prediction of pesticide behavior in soil by means of simple field tests.
AB  - A simple method is given for forecasting the reaction under different soil and
      site conditions of 106 pesticides with known binding strength by humus and clay
      in relation to pH and with known volatility and aerobic and anaerobic
      degradability. The method is based on easy-to-determine soil characteristics
      (texture, humus content, pH, groundwater table) and meteorological data (mean
      temperature, climatic water balance). It is possible to use this method to
      predict the environmental risk, especially the risk of contamination, and the
      groundwater pollution potential of a particular pesticide for a particular site
      in the field. In addition, recommendations for food contamination are given. This
      simple approach is suitable for use in on-site consultations. A reduction in
      pesticide input into near-surface groundwater can be expected when the
      recommendations derived from the model are applied. The use of this pragmatic
      model by farmers increases the awareness of the vulnerability of the groundwater
      recourse.

PMID- 7507823
TI  - Chemometrical evaluation of multispecies-multichemical data by means of graphical
      techniques combined with multivariate analyses.
AB  - A new method combining graphical displays with principal component analysis has
      been used to evaluate published data on the toxicity of seven chemicals to 14
      species (17 testing procedures) of aquatic biota. The results reflect the
      usefulness of simple graphical approaches for analyzing the structure of
      environmental data sets. Thus, the study indicates the importance of end point
      selection and underlines some relationships among the species and chemicals.

PMID- 7507824
TI  - Bimolecular OH rate constants of organic compounds in solution. 2. Measurements
      in 1,2,2-trichlorotrifluoroethane using hydrogen peroxide as an OH source.
AB  - Semivolatile organic compounds (SOC) occur in the troposphere either adsorbed at
      aerosol particles or in the free gas phase, depending on temperature, vapor
      pressure of the compound, and total particular surface. In order to estimate the
      abiotic degradation of such compounds, the OH reaction rate constant must be
      known, which cannot be measured directly in the gas phase at the relevant
      temperature due to experimental difficulties. In the method proposed here, the
      inert solvent 1,1,2-trichlorotrifluoroethane is used as the reaction medium and
      hydrogen peroxide as photolytic OH source. Relative reaction rates can be
      measured, using a reference compound of known kOH air. The relative rates can be
      converted into absolute ones due to the 1:1 relationship observed by Dilling,
      Gonsior, Boggs, and Mendoza (1988) Environ. Sci. Technol. 22, 1447-1453, between
      the relative rates in the inert solvent and those in the gas phase.

PMID- 7507825
TI  - Role of galanin in stimulation of pituitary luteinizing hormone secretion as
      revealed by a specific receptor antagonist, galantide.
AB  - In this study, a specific galanin (GAL) receptor antagonist, galantide, was
      employed to evaluate the role of endogenous GAL in episodic basal and phasic LH
      release in rats. To assess the specificity of galantide, a series of experiments
      was performed. In the first experiment, we observed that administration of GAL
      (0.62 nm) intracerebroventricularly (icv) in ovarian steroid-primed
      ovariectomized (ovx) rats rapidly increased plasma LH levels between 10-30 min,
      and prior injection of galantide icv (5 nm) blocked the GAL-induced LH release.
      In the second experiment, galantide inhibited the GAL-evoked in vitro release of
      LHRH from the median eminence-arcuate nucleus (ME-ARC) of ovarian steroid-primed
      ovx rats. In addition, galantide on its own significantly decreased the basal
      efflux of LHRH from the ME-ARC of similarly treated rats, thereby suggesting that
      even the basal LHRH secretion may be a GAL-dependent event. In the third
      experiment, the effects of galantide on the phasic LH surge elicited by
      progesterone (P) in estradiol benzoate-primed ovx rats and that occurring
      spontaneously on proestrus were examined. Ovx rats bearing icv cannulae were
      primed with estradiol benzoate (30 micrograms/rat, sc) and 2 days later received
      a P (2 mg/rat, sc) injection at 1000 h to evoke a LH surge in the afternoon.
      Galantide (1 or 5 nm) in 3 microliters saline or saline was injected icv at 1300,
      1400, and 1500 h. The results showed that the two dosages of galantide suppressed
      the LH surge in the afternoon. On the other hand, only a very high dose of
      galantide (15 nm) injected iv at 1300, 1400, and 1500 h blunted the P-induced LH
      hypersecretion. Central injections of galantide (1 or 5 nm) at 1300, 1400, and
      1500 h on proestrus also inhibited the preovulatory LH surge and significantly
      reduced the numbers of rats ovulating the following day. In the final experiment,
      the role of GAL receptors in modulation of episodic LH release was analyzed in
      ovx rats. The results showed that an injection of galantide (5 nm, icv)
      significantly decreased both the mean LH levels and the amplitude of LH episodes
      during the 3-h observation period. Cumulatively, these results show that normally
      GAL stimulates LHRH release by activation of a specific receptor located in the
      ME-ARC, and that GAL may be a key excitatory signal in the hypothalamic neural
      circuitry involved in the regulation of basal episodic and phasic LHRH secretion
      in cycling female rats.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7507826
TI  - Interrelationship of changes in islet nicotine adeninedinucleotide, insulin
      secretion, and cell viability induced by interleukin-1 beta.
AB  - Complete loss of pancreatic insulin function in insulin-dependent diabetes is
      thought to be due to an autoimmune cytokine-mediated destruction of the beta
      cell. The effects of several classes of agents on interleukin-1 beta (IL-1 beta)
      induced suppression of insulin secretion, beta-cell NAD levels, and beta-cell
      viability were examined. After overnight incubation of isolated rat islets with
      15 U/ml IL-1 beta and 11 mM glucose, sequential hourly insulin secretory
      responses to the same glucose concentration, 22 mM glucose, and 22 mM glucose
      plus forskolin were severely inhibited to 10-37% of the control value. Islet NAD
      levels were also sharply reduced to 43% of the control value after 24-h exposure
      to IL-1 beta, but not after 1 or 3 h, demonstrating the same time course as that
      for inhibition of insulin secretion. Exposure to IL-1 beta also decreased islet
      cell viability measured as trypan blue exclusion. Only 1 mM N-methyl arginine, an
      inhibitor of nitric oxide synthase, completely protected all three parameters of
      beta-cell function from damage by IL-1 beta. Nicotinamide and thymidine prevented
      the IL-1 beta-induced loss of cell viability and suppression of NAD, but had no
      effect on sustaining insulin secretion. Antioxidants, steroids, and several
      neuropeptides also did not prevent inhibition or restore the secretory response.
      Thus, the loss of the secretory response appears to be more narrowly restricted
      to nitric oxide radical damage induced by exposure to IL-1B.

PMID- 7507827
TI  - Gonadotropin-releasing hormone causes transcriptional stimulation followed by
      desensitization of the glycoprotein hormone alpha promoter in transfected alpha
      T3 gonadotrope cells.
AB  - Pulsatile GnRH regulates the biosynthesis and secretion of gonadotropins.
      Continuous administration of GnRH is known to desensitize gonadotropin secretion,
      but its effects on gonadotropin gene expression are less well characterized. We
      used a cell line of gonadotrope lineage (alpha T3 cells) to examine GnRH
      regulation of glycoprotein hormone alpha-subunit gene transcription. The alpha
      subunit promoter, linked to a luciferase reporter gene (alpha LUC), was stably
      transfected into alpha T3 cells. Treatment with GnRH stimulated alpha LUC
      activity 3-fold. Stimulation of alpha LUC by GnRH was transient, with maximal
      activity after 6 h of treatment, followed by a return to baseline after 24 h.
      Stimulation of alpha-promoter activity by GnRH was inhibited entirely by a 10
      fold molar excess of antide, a GnRH antagonist. Antide partially blocked GnRH
      stimulation even when added 4 h after GnRH, suggesting that a brief exposure to
      GnRH is not sufficient for maximal transcriptional stimulation. alpha LUC
      activity was also stimulated by treatment with 8-bromo-cAMP (3.5-fold), phorbol
      12-myristate 13-acetate (TPA; 2.6-fold), or Bay K 8644 (3.3-fold). To assess
      whether the transient nature of GnRH stimulation was due to transcriptional
      desensitization, cells were pretreated with GnRH, followed by a second treatment
      with GnRH, cAMP, TPA, or Bay K. After pretreatment with GnRH, no further
      stimulation was seen after the addition of GnRH or TPA, but alpha LUC activity
      was further stimulated after the addition of either cAMP or Bay K. These findings
      indicate that the pathway for transcriptional activation by GnRH is desensitized
      and suggest that GnRH also desensitizes TPA-mediated stimulation. Similarly,
      pretreatment with TPA, but not cAMP or Bay K, prevented subsequent stimulation by
      GnRH. We conclude that GnRH transiently stimulates alpha gene transcription and
      that desensitization occurs with continuous exposure to GnRH, probably because of
      down-regulation of the protein kinase-C pathway.

PMID- 7507828
TI  - Regulation of the ectopically expressed human glycoprotein alpha-subunit gene in
      the human hepatoma cell line NPLC.
AB  - The human glycoprotein alpha-subunit is the common subunit of the heterodimeric
      hormones CG (hCG), TSH, LH, and FSH. Human glycoprotein alpha-subunit is produced
      eutopically in placenta, pituitary, and choriocarcinoma and ectopically in a
      large variety of human tumors. We report ectopic glycoprotein alpha-subunit
      messenger RNA (mRNA) and peptide production in the human hepatoma cell line,
      NPLC. Neither hCG beta mRNA nor intact hCG peptide was detected. Antimetabolite
      regulation of glycoprotein alpha-subunit expression in NPLC cells resembled that
      found in choriocarcinoma cells in that it was stimulated by hydroxyurea. In
      addition, glycoprotein alpha-subunit mRNA expression and transcription in NPLC
      were stimulated by activators of the protein kinase A and C second messenger
      pathways, as well as by glucocorticoid. Glucocorticoid augmented glycoprotein
      alpha-subunit gene transcription by phorbol ester and forskolin, in contrast to
      its simultaneous inhibitory effect on phorbol ester activation of the CRH gene,
      which is also ectopically expressed in these cells. Glucocorticoid thus modulates
      the activation of these genes by phorbol ester in opposite directions, despite
      their identical cellular context. The NPLC cell line provides a new model for the
      study of human glycoprotein alpha-subunit gene regulation and free glycoprotein
      alpha-subunit secretion. In addition, it should be useful for investigating the
      role that specific cis-acting DNA sequences play in glucocorticoid modulation of
      gene induction by second messenger pathways.

PMID- 7507829
TI  - Inhibition of protein synthesis and hormone-sensitive steroidogenesis in response
      to hydrogen peroxide in rat luteal cells.
AB  - Hydrogen peroxide (H2O2) is generated in the corpus luteum at functional luteal
      regression and produces rapid antigonadotropic effects in rat luteal cells.
      However, the mechanism by which peroxide interrupts LH- and cAMP-sensitive
      progesterone synthesis is unknown. The post-cAMP site of H2O2 action is due to
      the reduced cholesterol availability in mitochondria, and this process is well
      known to be dependent on protein synthesis. Therefore, we examined whether H2O2
      may interfere with protein and RNA synthesis, and whether such responses may be
      associated with inhibition of steroidogenesis. Incorporation of radiolabeled
      amino acids into luteal proteins was inhibited in response to H2O2 in a time- and
      dose-dependent manner, and these doses are similar to those that inhibit
      progesterone synthesis, shown earlier in the identical paradigm. The inhibitory
      effect of H2O2 on amino acid incorporation was not due to increased protein
      degradation, impaired transport of amino acids, or depletion of cellular ATP
      levels. H2O2 also inhibited RNA synthesis, increased RNA degradation, and
      impaired the efficiency of mRNA as a translation template. The time course for
      the inhibitory effect of H2O2 on protein and RNA synthesis was very rapid and
      coincident with inhibition of steroidogenesis. Inhibition of protein and RNA
      synthesis and steroidogenesis were reversed by preincubation of cells with the
      cell-permeable metal chelator o-phenanthroline, which implicates metal-dependent
      radical generation as the probable mediator of these actions of H2O2. We conclude
      that the target of the post-cAMP site of peroxide-induced inhibition of cAMP
      dependent steroidogenesis is the inhibition of rapidly inducible proteins that
      are known to mediate translocation of cholesterol within mitochondria, where it
      is used as a substrate for pregnenolone synthesis.

PMID- 7507830
TI  - Cadherins and cadherin-associated molecules in the developing and maturing rat
      testis.
AB  - The calcium-dependent class of cell adhesion molecules known as cadherins mediate
      homotypic cell interactions in most epithelia. We have now investigated the
      expression and distribution of cadherins and cadherin-associated molecules in the
      developing and maturing rat testis. E-Cadherin was not detected in the
      seminiferous tubule at any time in development or in the adult. In contrast,
      Leydig cells expressed E-cadherin between day 15 of gestation and postnatal day
      3. alpha- and beta-catenins were expressed throughout the developing testis, but
      were particularly prominent in Leydig cells. In the maturing testis, alpha
      catenin and plakoglobin became progressively more restricted to the basal part of
      the seminiferous epithelium and by 23 days exhibited a pattern characteristic of
      the Sertoli cell junctional complex. beta-Catenin recruitment to the Sertoli cell
      junctional complex was not complete until 60 days. alpha-Catenin and plakoglobin
      were not present at sites of Sertoli cell-germ cell contacts. Northern blot
      analysis of testicular RNA showed three mRNA species hybridizing with N-cadherin
      cDNA. A pan-cadherin antibody specific for a region of the highly conserved C
      terminal of all cadherins stained sites of Sertoli-spermatocyte and Sertoli-round
      spermatid contact in the adult rat seminiferous epithelium, but did not stain the
      Sertoli cell tight junctional complex. Western blots of testicular extracts
      indicated that the molecule(s) recognized by these antibodies had an approximate
      molecular mass of 120 kilodalton, typical of members of the cadherin family.
      Therefore, although Sertoli cells do not express E-cadherin, another member(s) of
      the cadherin family is present in the testis, but may not be directly involved in
      tight junction dynamics as in other cells. Instead, cadherin-mediated adhesion is
      likely to be involved in Sertoli cell-germ cell interactions. As catenins are not
      present at these sites, our results suggest a catenin-independent role of
      cadherins in germ cell adhesion to Sertoli cells.

PMID- 7507831
TI  - Regulation of progesterone receptor gene expression in MCF-7 breast cancer cells:
      a comparison of the effects of cyclic adenosine 3',5'-monophosphate, estradiol,
      insulin-like growth factor-I, and serum factors.
AB  - We have compared regulation of progesterone receptor (PR) gene expression in MCF
      7 human breast cancer cells by cAMP and that by estradiol (E2) and insulin-like
      growth factor-I (IGF-I). Treatment of cells with 8-bromo-cAMP or agents known to
      activate protein kinase-A, namely cholera toxin plus 3-isobutyl-1-methylxanthine
      (CT plus IBMX; which increased intracellular cAMP > 10-fold) evoked an increase
      in PR protein levels as did treatment with IGF-I or E2. Increases in PR caused by
      IGF-I were not accompanied by increases in PR mRNA, whereas PR mRNA levels were
      markedly induced by E2 and CT plus IBMX, showing regulation at different levels
      by these agents. The increases in PR mRNA evoked by E2 or CT plus IBMX were
      almost completely abolished by treatment with antiestrogen. Treatment with
      cycloheximide inhibited CT- plus IBMX-mediated PR mRNA stimulation, but not the
      induction of E2, indicating that the PR mRNA response to cAMP is not a primary
      one and probably requires de novo protein synthesis. Distinct effects of serum
      were observed on the expression of PR in MCF-7 cells. PR mRNA and protein were
      consistently elevated when cells were cultured under low serum conditions (0-0.5%
      charcoal dextran-treated calf serum) and were reduced as the serum concentration
      was increased, suggesting that a serum factor(s) repress constitutive PR levels.
      Also, the ability of CT plus IBMX to stimulate PR declined markedly for cells
      grown in medium containing higher (5%) serum levels; by contrast, the ability of
      E2 to induce PR was increased at the higher serum concentration. Thus, unknown
      serum factors interfere with the action of cAMP in up-regulating PR, whereas
      serum factors are important for the effectiveness of E2 in stimulating PR. These
      observations indicate that regulation of PR occurs at different levels by several
      factors (cAMP, E2, and IGF-I) and imply that cAMP, serum factors, and growth
      factors, such as IGF-I, in addition to E2 will be of importance in determining PR
      levels and, hence, cell sensitivity to progestins.

PMID- 7507832
TI  - Expression and sexual dimorphism of galanin messenger ribonucleic acid in growth
      hormone-releasing hormone neurons of the rat during development.
AB  - In the rat, the secretion of GH is episodic and sexually dimorphic. The
      development and regulation of this patterning of GH secretion are governed by the
      reciprocal influence of the hypothalamic peptide somatostatin and GH-releasing
      hormone (GHRH). Galanin is a neuropeptide that is colocalized with GHRH in
      hypothalamic neurons and is thought to be involved in generating the episodic
      pattern of GH secretion. We hypothesized that galanin mRNA expression in GHRH
      neurons increases over development in both sexes, and that in the adults, galanin
      expression in GHRH neurons is greater in males than in females. To test these
      hypotheses, we used a double label in situ hybridization procedure to detect and
      measure galanin mRNA expression in GHRH neurons in the rat brain. GHRH mRNA
      positive cells were visualized by an alkaline phosphatase color reaction, and
      galanin mRNA levels were measured by counting autoradiographic grains over
      individual GHRH mRNA-positive cells. Galanin mRNA coexpression was found in GHRH
      mRNA-containing cells of the arcuate nucleus, periarcuate area, and ventromedial
      hypothalamus. In both males and females there was a significant increase in
      galanin mRNA in GHRH neurons over development. Galanin mRNA levels in GHRH
      neurons of 10- and 25-day-old rats were higher in females than in males [10-day
      old: females, 12 +/- 2; males, 6 +/- 1 grains/cell (P < 0.05); 25-day-old:
      females, 28 +/- 4; males, 15 +/- 3 grains/cell (P < 0.02)]. In adults (70 days),
      galanin mRNA levels in GHRH neurons were significantly higher in males than in
      females (males, 54 +/- 4; females, 32 +/- 3 grains/cell; P < 0.005). In the adult
      rat, galanin mRNA levels in the individual hypothalamic areas exhibited a
      significant sexual dimorphism in the arcuate nucleus and periarcuate area, with
      higher levels in the male, whereas no sexual dimorphism was observed in the
      ventromedial hypothalamus. To determine whether galanin gene expression is
      influenced by circulating levels of testosterone, we measured galanin mRNA levels
      in castrated male rats with and without testosterone replacement. Castration
      reduced galanin message levels in GHRH neurons (intact, 73 +/- 6; castrate, 57 +/
      4 grains/cell), and although this reduction was not statistically significant (P
      = approximately 0.07), testosterone replacement significantly increased galanin
      message content (castrate/sham, 58 +/- 4 grains/cell; castrate plus testosterone
      replacement, 77 +/- 5 grains/cell; P < 0.02) to intact levels (intact, 73 +/- 6
      grains/cell). In summary, galanin message expression in GHRH neurons of both male
      and female rats increases over development.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7507833
TI  - Regulation of glycoprotein hormone free alpha-subunit secretion and intracellular
      alpha-subunit content in primary pituitary cells.
AB  - The effects and interactions of GnRH, TRH, a cAMP analog, a protein kinase-C
      (PKC) activator, a calcium ionophore, and a calcium channel blocker on pituitary
      glycoprotein hormone free alpha-subunit secretion and intracellular free alpha
      subunit content were investigated. Treatment of dispersed rat pituitary cells
      with GnRH (100 nM) effected a time-dependent release of alpha-subunit, reaching a
      4.5-fold increase (P < 0.05) at 24 h. Smaller effects were observed with TRH (10
      nM). A rapid and progressive fall in intracellular alpha-subunit content was
      observed for 8 h after stimulation with GnRH (61% decrease; P < 0.05) or TRH (55%
      decrease; P < 0.05), which then remained constant at 24 h. The cAMP analogue 8
      bromo-cAMP augmented a late release of alpha-subunit (4.5-fold increase at 24 h;
      P < 0.05) without affecting levels of alpha-subunit within the cells. Co-addition
      of 8-bromo-cAMP with GnRH or TRH arrested the marked fall in intracellular alpha
      subunit seen with GnRH or TRH alone. These results suggest that although cAMP is
      capable of stimulating alpha-subunit secretion and maintaining cell content in
      the face of GnRH- and TRH-stimulated secretion, it does not mediate their effects
      on alpha-subunit. Like GnRH, the PKC activator 12-O-tetradecanoyl-phorbol-13
      acetate (TPA) rapidly stimulated alpha-subunit secretion (1.7-fold increase at 4
      h; P < 0.05) and progressively lowered cell content over 24h (73% decrease; P <
      0.01). This similarity of action and the lack of demonstration of additive
      effects of TPA with GnRH or TRH imply a role for PKC as a mediator of GnRH and
      TRH action on alpha-subunit. Using verapamil (50 microM) to block L-type calcium
      channels had no effect on either basal or GnRH-stimulated alpha-secretion over 24
      h. The calcium ionophore A23187 (3 microM) blocked the stimulatory effects of
      GnRH on alpha-subunit release and alone inhibited free alpha-subunit secretion
      (28% decrease at 24 h; P < 0.05). Our results suggest that neither cAMP nor an
      influx of extracellular calcium mediates the effects of GnRH or TRH on free alpha
      subunit secretion. Accordingly, we postulate that PKC is involved in the actions
      of GnRH and TRH on alpha-subunit in rat pituitary cells, although further studies
      are required in PKC-depleted cells to confirm this hypothesis.

PMID- 7507834
TI  - The augmentation of insulin-like growth factor-I messenger ribonucleic acid in
      cultured rat hepatocytes: activation of protein kinase-A and -C is necessary, but
      not sufficient.
AB  - In previous studies it was shown that bovine GH (bGH) and glucagon, when
      individually added to primary rat hepatocyte cultures, modestly stimulated IGF-I
      mRNA levels 1.8- to 2.5-fold, but when combined, synergized to stimulate IGF-I
      mRNA levels by 10- to 12-fold. In the present study we have explored further the
      mechanism of this effect in primary rat hepatocyte cultures. Like glucagon, the
      addition of 3-isobutyl-1-methylxanthine (100 microM) or (Bu)2cAMP (150 microM)
      augmented IGF-I mRNA levels 1.8- to 2.0-fold, but when combined with bGH (50
      ng/ml), they augmented levels up to 12-fold. The half-life of IGF-I mRNA,
      determined by incubating hepatocytes with actinomycin-D was 12 h. Although bGH
      did not affect the decay rate, glucagon (100 ng/ml) or (Bu)2cAMP (100 microM)
      reduced the rate of loss by about 70%. 4 beta-Phorbol 12 beta-myristate 13 alpha
      acetate minimally stimulated IGF-I mRNA levels 1.2- to 1.4-fold, but displayed no
      synergism when added with bGH, glucagon, or (Bu)2cAMP. The stimulatory effect of
      bGH plus glucagon was inhibited 80% after preincubation with 4 beta-phorbol 12
      beta-myristate 13 alpha-acetate (10 microM) for 24 h. The addition of
      staurosporine, sphingosine, or H-7 [1-(5-isoquinolinyl sulfonyl)2-methyl
      piperazine] inhibited the stimulatory effect of bGH plus glucagon on hepatocyte
      IGF-I mRNA by 80%, 90%, and 85%, respectively. Preincubation with cycloheximide
      (10 micrograms/ml) blocked the synergistic effect of bGH plus either glucagon or
      (Bu)2cAMP by 65-80%. The effect of glucagon, mediated via the activation of
      adenylate cyclase, involves in part the posttranscriptional stabilization of IGF
      I mRNA levels. The effect of GH, mediated in part by the activation of protein
      kinase-C, appears to be at the level of transcription. The synergistic
      augmentation of hepatocyte IGF-I mRNA levels by GH and glucagon involves the
      activation of PKA and PKC, but also appears to require the synthesis of one or
      more protein(s).

PMID- 7507835
TI  - Functional analysis of glucocorticoid and insulin response sequences in the rat
      insulin-like growth factor-binding protein-1 promoter.
AB  - Insulin-like growth factor-binding protein-1 (IGFBP-1) is produced by the liver
      and regulated by glucocorticoids and insulin at the level of gene transcription.
      To identify DNA sequences mediating the effects of glucocorticoids and insulin on
      IGFBP-1 promoter activity we created luciferase reporter gene constructs and
      performed transfection studies in H4IIE hepatoma cells. Initial studies confirmed
      that the IGFBP-1 promoter is functional when inserted in the correct orientation,
      but not in the reverse orientation. Dexamethasone (DEX) increased promoter
      activity 10-fold, and insulin reversed this effect of DEX by 85% at 8 h. The
      effects of DEX were abolished when constructs were truncated to 89 bases from the
      RNA cap site, and DNase footprinting with the DNA-binding domain of the human
      glucocorticoid receptor identified an imperfect palindrome containing two
      receptor-binding sites separated by three nucleotides typical of a glucocorticoid
      response element (GRE) at this location. Mutation of either binding site (or half
      site) disrupted the effects of DEX, confirming that this sequence functions as a
      GRE. Two other regions of the promoter also footprinted with the glucocorticoid
      receptor protein and contained sequences consistent with glucocorticoid receptor
      binding sites; however, neither of these footprints contained the full structure
      expected of a functional GRE, and neither mutation nor deletion of these other
      sequences altered the effects of DEX on promoter activity. To identify the DNA
      sequences required for the effects of insulin on glucocorticoid-stimulated
      promoter activity, we created internal deletions throughout the IGFBP-1 promoter
      region. Deletion of the 22-basepair (bp) sequence immediately 5' from the GRE
      disrupted the effect of insulin and appeared to increase basal promoter activity
      at least 2-fold in each of eight experiments (P < 0.001 vs. intact promoter).
      This region of the IGFBP-1 promoter contains a 19-bp palindrome
      (CAAAACAAACTTATTTTG) that overlaps the 5'-end of the GRE and is fully conserved
      in the human IGFBP-1 promoter. Each half of this palindrome resembles previously
      identified insulin response sequences, and deletion/mutation analysis suggests
      that each half may contribute to the effects of insulin on promoter activity. Gel
      shift studies confirmed that this palindrome binds H4IIE nuclear proteins. In
      summary, we have identified a GRE in the 5'-promoter region of the rat IGFBP-1
      gene approximately 90 bp up-stream from the RNA cap site as well as a contiguous
      22-bp region that plays a critical role in mediating the effects of insulin on
      glucocorticoid-stimulated promoter activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7507836
TI  - Both low sodium and high potassium intake increase the level of adrenal
      angiotensin-II receptor type 1, but not that of adrenocorticotropin receptor.
AB  - Angiotensin-II (AII), a component of the renin-angiotensin system, is the major
      factor that regulates the formation of aldosterone in the adrenal cortex zona
      glomerulosa (ZG). The activity of this system is increased by an increase in
      potassium intake or a decrease in sodium intake. Using immunoblotting analysis,
      we determined whether these ions affect the expression of type 1 AII receptors
      (AT1) and compared the results thus obtained with the AT1 receptor mRNA levels.
      We also studied the interrelation among AII, AT1 receptors, cytochrome P450
      aldosterone synthase (P450c18), and plasma aldosterone levels in rats fed a
      normal diet or a low sodium or high potassium diet with or without captopril, an
      inhibitor of angiotensin-converting enzyme, for 7 days. The effects of ions on
      the level of ACTH receptor mRNA were also analyzed. We found that a low sodium
      intake increased plasma aldosterone levels from 5.5 to 236 ng/dl and led to 2.3-
      and 3.7-fold increases in the levels of adrenal ZG AT1 receptor protein and AT1
      receptor mRNA, whereas a 11.8-fold increase was found in the level of P450c18
      mRNA. Captopril almost completely reversed these effects. We have shown that a
      high potassium intake increased plasma aldosterone levels to 25.9 ng/dl and also
      led to 1.84- and 1.95-fold increases in the level of ZG AT1 receptor protein and
      AT1 receptor mRNA, whereas the ZG P450c18 mRNA level was increased 3.5-fold. The
      plasma aldosterone level of animals fed a high diet of potassium and captopril
      was still higher than that in control animals at 16.6 ng/dl, and the levels of ZG
      AT1 receptor and P450c18 mRNAs were only slightly less than those of the high
      potassium groups, indicating that captopril did not efficiently block aldosterone
      formation under these conditions. ACTH receptor mRNA levels remain unaffected by
      either low sodium or high potassium intake. Collectively, these results indicate
      that the increased aldosterone secretion induced by low sodium or high potassium
      intake involves concomitant increases in AT1 receptor and P450c18 mRNAs, which
      are effectively translated into their respective proteins, and that the
      expression of both proteins is mediated in part by AII.

PMID- 7507838
TI  - Functional specificity for salmon gonadotropin-releasing hormone (GnRH) and
      chicken GnRH-II coupled to the gonadotropin release and subunit messenger
      ribonucleic acid level in the goldfish pituitary.
AB  - GnRH is the key regulator of reproduction in the vertebrates. In this study, we
      investigated the release and synthesis of maturational gonadotropin hormone (GTH
      II) stimulated by native GnRH forms, salmon GnRH (sGnRH) and chicken GnRH-II
      (cGnRH-II), in the goldfish pituitary. The experimental approach was to study the
      differences between desensitization induced by sGnRH and cGnRH-II administered in
      homologous and heterologous fashion. Pulsatile alternate treatments with sGnRH
      and cGnRH-II (i.e. sGnRH/cGnRH-II or cGnRH-II/sGnRH) at 10(-8) M (every 30 min)
      resulted in a lower degree of desensitization compared with homologous treatments
      with either sGnRH or cGnRH-II (sGnRH/sGnRH or cGnRH-II/cGnRH-II), or when
      combined together (sGnRH+cGNRH-II). We also investigated the effects of
      continuous treatments with sGnRH and cGnRH-II, administered in a homologous or
      heterologous fashion. Increasing concentrations of either sGnRH or cGnRH-II (10(
      8)-10(-6) M) administered continuously (60 min) in a homologous fashion resulted
      in significant desensitization of the pituitary GTH-II release. Alternate
      continuous treatments with sGnRH and cGnRH-II (i.e. sGnRH/cGnRH-II/sGnRH or cGnRH
      II/sGnRH/cGnRH-II) resulted in lower degree of desensitization compared to
      homologous treatments, particularly at lower doses. We further investigated the
      effects of sGnRH and cGnRH-II on GTH-II beta and GTH-II alpha subunit messenger
      RNA (mRNA) levels in the goldfish pituitary. In sexually regressed animals, sGnRH
      treatment (4 micrograms/fish) increased the accumulation of GTH-II beta and GTH
      II alpha mRNA, whereas cGnRH-II treatment was without effect. In sexually mature
      animals, however, both cGnRH-II and sGnRH stimulated accumulation of GTH-II beta
      and GTH-II alpha mRNA, with cGnRH-II exerting a greater effect on GTH-II subunit
      mRNA production. These results suggest a differential control of GTH-II subunit
      gene expression or mRNA stabilization by sGnRH and cGnRH-II in the goldfish
      pituitary based on the stage of gonadal recrudescence. In general, the present
      findings support the hypothesis that sGnRH and cGnRH-II regulate the release and
      synthesis of GTH-II through different receptor-effector mechanisms in the
      goldfish pituitary.

PMID- 7507837
TI  - The D2 dopamine receptor mediates inhibition of growth in GH4ZR7 cells:
      involvement of protein kinase-C epsilon.
AB  - The D2 dopamine agonist, bromocriptine, has been used as treatment for human PRL
      secreting pituitary adenomas. The result of bromocriptine treatment is often a
      substantial reduction of tumor mass, suggesting that the dopamine agonist is
      acting as an antiproliferative agent. This action can be observed with a clonal
      pituitary tumor cell line. The agonist activation of the D2 dopamine receptor
      inhibits the growth of GH4ZR7 cells, a GH4C1 cell line stably transfected with
      the cDNA encoding the short form of the D2 dopamine receptor. This effect of
      dopamine was not sensitive to overnight treatment with 100 ng/ml pertussis toxin.
      Treatment of GH4ZR7 cells with the phorbol ester 4 beta-phorbol 12,13-didecanoate
      resulted in the loss of dopaminergic inhibition of growth, whereas treatment with
      4 alpha-phorbol 12,13-didecanoate had no effect. Inhibitors of protein kinase-C
      (PKC), such as staurosporine and H7, also blocked the effect of dopamine. Down
      regulation of cellular PKC by phorbol ester treatment resulted in a complete loss
      of dopaminergic inhibition of growth. Long term treatment of GH4ZR7 cells with
      TRH results in a specific down-regulation of the epsilon form of PKC and
      abolished the ability of dopamine to inhibit growth. These results suggest that
      PKC epsilon is involved in mediating the antiproliferative effects of dopamine.
      This mediation of growth appears to be through a novel signaling pathway for the
      D2 dopamine receptor.

PMID- 7507839
TI  - Purification and characterization of the acid-labile subunit of rat serum insulin
      like growth factor binding protein complex.
AB  - Circulating insulin-like growth factor (IGF) binding protein-3 (IGFBP-3), when
      occupied by IGF-I or IGF-II, combines with an acid-labile glycoprotein subunit
      (ALS) to form a high molecular weight complex. In this study, ALS from rat serum
      has been purified and its properties investigated. Purification involved ion
      exchange chromatography, and affinity chromatography on an IGF-I-IGFBP-3 column,
      yielding almost 1 mg ALS from 100 ml serum. Amino-terminal sequencing confirmed
      the prediction from previous complementary DNA analysis but indicated that the
      protein may circulate in a truncated form. Rat ALS was almost as potent as human
      ALS in binding to human IGF-I-IGFBP-3 complex (association constant, 2.3 nM-1). A
      sensitive RIA was developed, with high specificity for rodent ALS. Serum ALS rose
      from 3 micrograms/ml in 2-day-old rats to more than 40 micrograms/ml at 10 weeks,
      with no sex difference. GH-deficient rats showed 60-75% lower values than
      controls. This study shows rat ALS to have similar binding properties, and age
      and GH dependence, to human ALS. The new RIA will facilitate studies of IGF and
      IGFBP regulation in the rat.

PMID- 7507840
TI  - Distinct expression patterns of insulin-like growth factor binding proteins 2 and
      5 during fetal and postnatal development.
AB  - Insulin-like growth factors (IGFs), when isolated from serum or tissue fluids,
      are usually found as part of a protein complex which also contains one of several
      IGF binding proteins (IGFBPs). Although some IGFBPs have been shown to alter
      interactions of IGFs with their receptors in vitro and can modify the responses
      of cultured cells to exogenous IGFs, the in vivo functions of IGFBPs remain
      unclear. This study examines expression of a recently described IGFBP gene, IGFBP
      5, in the rat embryo and fetus and in selected adult tissues. Embryonic IGFBP-5
      messenger RNA (mRNA) can be detected as early as embryonic day 10.5 and has an
      mRNA expression pattern distinct from the previously characterized pattern of
      IGFBP-2 mRNA expression. Major sites of IGFBP-5 expression during early
      postimplantation stages of development include the notochord, the floor plate,
      regions of the surface ectoderm, muscle precursor cells, and specific axial
      regions of neuroepithelium. Later in development IGFBP-5 mRNA is found in several
      regions of the central nervous system, including the proliferative zone of the
      external granule layer of the cerebellum and the mitral neurons of the olfactory
      bulb, as well as in muscle precursor populations of the developing limb, and in
      most cells of the anterior pituitary. In addition, only a subset of pituicytes in
      the adult posterior pituitary express IGFBP-5, which provides the first evidence
      that this cell population is biochemically heterogeneous. Taken together, these
      data suggest functions for IGFBP-5 during development of several organ systems.

PMID- 7507841
TI  - Differential expression of epidermal growth factor receptor (EGF-R) gene and
      regulation of EGF-R bioactivity by progesterone and estrogen in the adult mouse
      uterus.
AB  - The present study examined several aspects of epidermal growth factor receptor
      (EGF-R) in the mouse uterus during the peri-implantation period and after ovarian
      hormone treatment of adult ovariectomized mice. The cell-specific distribution,
      regulation of expression, and binding kinetics were assessed by
      immunohistochemistry, Northern blot analysis, and ligand binding assays,
      respectively. Affinity cross-linking studies ascertained the size of the EGF-R,
      and its bioactivity was examined by determining EGF-dependent subcellular protein
      tyrosine kinase activity and receptor autophosphorylation. In the intact uterus
      and separated cell types, EGF-R was detected in the stroma, deciduum, and
      myometrium, but not in the luminal or glandular epithelium. Uterine EGF-R mRNA
      transcript profiles showed some differences between pregnant and ovariectomized
      mice regardless of steroid hormone treatments. Two major [6.5- and 2.7-kilobase
      (kb)] and two less abundant (9.6- and 5.0-kb) transcripts were detected in
      pregnant uterine poly(A)+ RNA. Three additional transcripts (< 2.0 kb) were
      detected in decidual poly(A)+ RNA, and a larger transcript (8.0 kb) was detected
      in uterine poly(A)+ RNA isolated from ovariectomized mice. Scatchard analysis of
      EGF binding also revealed apparent differences in binding kinetics between
      pregnant and ovariectomized mice, although EGF was cross-linked to a 170
      kilodalton protein under these conditions. Two classes (Kd, approximately 0.2 and
      approximately 2.0 nM) of binding sites were noted in pregnant mice, whereas a
      single class (Kd, approximately 1.0 nM) was found in ovariectomized mice. 17 beta
      Estradiol (E2) caused a rapid transient upregulation of uterine EGF-R mRNA levels
      and increased the number of EGF-binding sites in ovariectomized mice, as did an
      injection of progesterone (P4). However, the bioactivity of EGF-R could not be
      detected in uteri of ovariectomized mice treated with oil or P4. E2 treatment was
      found to be essential for EGF-R bioactivity. Taken together, the results suggest
      that in the adult mouse uterus, EGF-R status is influenced by factors other than
      P4 and E2, the epithelium is not the direct target for the actions of EGF-related
      growth factors as thought previously, the mitogenic effects of these growth
      factors on epithelial cells in vivo are perhaps mediated by other uterine cell
      types expressing EGF-R, and, lastly, these growth factors are not likely to be
      functional in the uterus in the absence of estrogen. The present observations are
      supportive of the concept of paracrine or juxtacrine interactions between EGF
      related growth factor ligands of luminal epithelial origin and blastocyst EGF-R
      in the process of implantation.

PMID- 7507842
TI  - The envelope glycoprotein of HIV-1 gp120 and human complement protein C1q bind to
      the same peptides derived from three different regions of gp41, the transmembrane
      glycoprotein of HIV-1, and share antigenic homology.
AB  - gp41, the transmembrane glycoprotein of HIV-1, has been shown to be non
      covalently associated with gp120. We have shown that it also binds human C1q. To
      analyze the interaction site(s) of gp41 with these two molecules, we established
      an enzyme-linked immunosorbent assay (ELISA) system using recombinant soluble
      gp41 [amino acids (aa) 539-684] and peptides thereof. In the cell-external part
      of gp41 three sites (aa 526-538, aa 590-613 and aa 625-655) were found to bind
      both gp120 and C1q. That gp120 and C1q use the same sites was evidenced by the
      fact that these proteins competed with each other for the same sites in
      recombinant soluble gp41 and gp41 peptides. It could be demonstrated by ELISA,
      that rabbit antibodies against human C1q recognized gp120, and rabbit antibodies
      against gp120 cross-reacted with C1q. Rabbit anti-gp120, HIV-1-positive human
      sera and anti-gp120 obtained from such sera agglutinated sensitized sheep
      erythrocytes with human C1q (EAC1q). These data suggest that in addition to
      functional homology between C1q and gp120 structural homology between these two
      molecules exists. This molecular mimicry might become the basis for
      immunologically relevant autoimmune phenomena.

PMID- 7507843
TI  - Role of CD40 antigen and interleukin-2 in T cell-dependent human B lymphocyte
      growth.
AB  - In the present study, we examined the participation of CD40 ligand (L)-CD40
      interaction in T cell-dependent B cell responses. To this end, purified B
      lymphocytes were cultured over irradiated CD4+ cloned T cells activated with
      immobilized anti-CD3 antibody. The anti-CD40 mAb 89 strongly blocked, in a
      specific fashion, both proliferation and Ig secretion of tonsil B cells.
      Interestingly, proliferation of surface (s)IgD+ B cell was significantly less
      inhibited by anti-CD40 than that of sIgD- cells. Preactivated T cells induced B
      cells to grow and secrete immunoglobulins preferentially in response to IL-2.
      This contrasts with the CD40 system where B cells are essentially responsive to
      IL-4 and IL-10 but not to IL-2 alone. Collectively, these data indicate that
      CD40L-CD40 interaction plays an important role in IL-2 mediated T cell-dependent
      B cell responses. However, the activation of a subset of sIgD+ cells may be
      independent of this interaction.

PMID- 7507844
TI  - T cell epitopes encompassing the mutational hot spot position 61 of p21 ras.
      Promiscuity in ras peptide binding to HLA.
AB  - Activated ras carry a point mutation either in codon 12, 13 or 61 which is tumor
      specific. Peptides derived from this oncoprotein are therefore potential tumor
      antigens. Essential for the feasibility of using ras-derived peptides in therapy
      of cancer is whether p21 ras-derived peptides can be processed, bind to human
      histocompatibility leukocyte antigen (HLA) and be recognized by T cells. Here we
      report the fine specificity and HLA restriction of several T lymphocyte clones
      (TLC) specific for a peptide which is derived from the second mutational hot spot
      in ras encoding residue 61. These TLC were generated from memory T cells present
      in the blood of a cancer patient and recognized a ras-derived peptide carrying
      Leu instead of Gln at residue 61. By sequencing of the T cell receptor (TcR)
      genes three sets of "sister" TLC carrying highly different TcR were identified.
      Two of the TLC recognized a peptide carrying the 61 Leu mutation presented by HLA
      DQ8 and one recognized the same peptide presented by HLA-DQ4. By using truncated
      peptides derived from residues 51 to 69 of p21 ras, partially overlapping minimal
      epitopes could be defined. All three TLC recognized the corresponding recombinant
      mutant p21 ras oncoprotein carrying Leu at residue 61 presented by autologous B
      lymphoblastoid cell lines (B-LCL). This demonstrates that naturally derived ras
      peptides from this region of p21 ras encompass the three epitopes recognized by
      the TLC. These results indicate that immunogenic ras-derived peptides may be used
      in immunotherapy of cancer where transforming ras oncoproteins are involved.

PMID- 7507845
TI  - A novel soluble form of mouse VCAM-1 is generated from a glycolipid-anchored
      splicing variant.
AB  - VCAM-1 is a cytokine-induced endothelial adhesion molecule which belongs to the
      immunoglobulin (Ig) superfamily and mediates the binding of various leukocytes.
      In addition to the 110-kDa form of VCAM-1, we have found four additional
      glycoproteins on mouse brain-derived endothelioma cells after stimulation with
      tumor necrosis factor-alpha (TNF-alpha), which are recognized by several
      monoclonal antibodies against VCAM-1. Biochemical analysis revealed that the two
      smaller proteins (35 kDa and 37 kDa) are intracellular precursors of the two
      larger forms (44 kDa and 45 kDa), that the 44 kDa and 45 kDa proteins are
      glycolipid-anchored at the cell surface and that they differ in their N
      glycosylation. Most likely they are identical to the recently identified
      glycolipid-anchored splice variant of VCAM-1, since they are recognized by the M3
      antiserum which we raised against a peptide from the unique protein domain of
      this splicing variant. With the help of this antiserum we could show by
      immunohistology that the corresponding VCAM-1 protein variant is induced in vivo
      by lipopolysaccharide (LPS) on endothelium of the mouse. In addition, we found a
      42-kDa soluble form of VCAM-1 in the serum of LPS-stimulated mice, which was
      recognized by the M3 antiserum. This soluble form was undetectable in the serum
      of unstimulated mice in contrast to the soluble 100-kDa form of VCAM-1 which was
      clearly detected in serum of unstimulated mice and only increased 2-3-fold upon
      stimulation with LPS. Thus, only the expression of the 42-kDa shredded form and
      not of the 100-kDa soluble form of VCAM-1 is strictly dependent on stimulation by
      LPS.

PMID- 7507847
TI  - B-T cell interactions modulate inhibitory effects of interleukin-4 on human B
      cell proliferation.
AB  - In this study, we investigated the role of B-T cell contacts in interleukin Ia
      mediated inhibition of human B lymphocyte proliferation induced by mitogenic
      doses of soluble anti-mu monoclonal antibody (mAb). We show that additional cross
      linking of B cell antigens, using Sepharose beads coated with anti-mu, anti-(IL)
      4 mAb (but not soluble mAb) or anti-CD40 antigen counteracted the inhibitory
      activity of IL-4. More importantly, cell contacts between B cells and activated T
      cells (but not unstimulated T cells) were sufficient to counteract IL-4-mediated
      inhibition of DNA synthesis. In addition, the inhibitory activity of IL-4 on
      chronic lymphocytic leukemia B cells stimulated with anti-mu and IL-2 was itself
      reduced by the presence of fixed activated T cells. Our data suggest that a major
      role for IL-4 would be to prepare B cells to receive additional mitogenic signals
      through cell contact interactions with activated T lymphocytes. When such
      interactions do not occur IL-4 may block DNA synthesis, preventing uncontrolled B
      cell proliferation.

PMID- 7507848
TI  - Okadaic acid blocks PDGF-induced proliferation of AKR-2B fibroblasts at the
      transition from G1- to S-phase.
AB  - Okadaic acid (OA) at 100 ng/ml completely inhibited platelet-derived growth
      factor (PDGF)-BB-induced DNA synthesis but had no effect on early signals, i.e.,
      PDGF receptor autophosphorylation or stimulation of inositolphosphate turnover. A
      detailed analysis using synchronized cells showed that OA acts at the transition
      from G1-phase to S-phase. These observations were confirmed by flow cytometric
      DNA analysis of asynchronously grown cells. Here cells were specifically arrested
      in the G1-phase.

PMID- 7507846
TI  - Interleukin-2 prevention of apoptosis in human neutrophils.
AB  - Evidence is presented that interleukin (IL)-2 maintains viability of human
      polymorphonuclear cells (PMN) in culture by preventing these cells from
      undergoing programmed cell death (PCD) and induces the synthesis of new RNA and
      protein. Our laboratory has recently discovered that human PMN constitutively
      express IL-2 beta receptor and more importantly, PMN are able to respond
      functionally to IL-2 by enhanced growth inhibitory activity against an
      opportunistic fungal pathogen, Candida albicans. We now report that IL-2 was able
      to interfere with the PCD process and reduce the number of apoptotic PMN to < 40%
      in 72-h culture. Freshly isolated PMN usually underwent a time-dependent aging
      process and > 80% of PMN cultured in medium alone for 72 h showed morphologic
      features of PCD as depicted by hematoxylin and eosin staining as well as by
      electron microscopy. During the PCD process, untreated PMN not only exhibited
      condensed nuclear structure and decrease in cell size, but also displayed DNA
      fragmentation. DNA fragmentation in PMN was prevented by IL-2. Prevention of PCD
      by IL-2 was associated with an increase in new RNA and protein synthesis in PMN,
      which may reflect cytokine induction, such as tumor necrosis factor, as we have
      recently shown. Thus, our data expands our current understanding of PMN in that
      they may be an active component of the immune system, with a longer life-span
      when activated than expected.

PMID- 7507849
TI  - Epithelial cells are an important source of tenascin in normal and malignant
      human breast tissue.
AB  - The extracellular matrix glycoprotein tenascin is limited to the periductal
      matrix of normal breast tissue but is markedly increased in both malignant and
      fibroadenomatous proliferations. It has been hypothesized that the changes in
      tenascin expression in these tissues are the result of epithelial induction of
      tenascin expression by the underlying mesenchyme. We have used Western and
      Northern blotting techniques to examine tenascin expression by normal and
      malignant mammary epithelial cells in culture. Normal mammary epithelial cells
      express tenascin in culture and incorporate the protein into the underlying
      matrix. The SV40-transformed mammary epithelial cell line HBL100 and some
      established mammary carcinoma cell lines also express tenascin. In contrast to
      normal mammary epithelial cells, carcinoma cells incorporate very little tenascin
      into the underlying matrix. To examine the source of tenascin expression in vivo,
      we have used in situ hybridization to demonstrate that the epithelial cells are a
      significant source of tenascin in both normal and malignant breast tissues.

PMID- 7507850
TI  - Exemption of satellite DNA from demethylation in immortalized differentiated
      derivatives of F9 mouse embryonal carcinoma cells.
AB  - DNA methylation in F9 embryonal carcinoma cells at various stages of retinoic
      acid-induced differentiation was compared to that in immortalized differentiated
      derivatives of this cell line. Different repetitive sequences, such as L1 LINE,
      GAPDH pseudogenes, and major and minor satellite DNA, lost their methylation to
      similar extents during F9 differentiation into parietal endoderm cells. In the
      immortalized derivatives 8a and P1, which phenotypically resemble F9 cells at
      intermediate stages of differentiation, methylation patterns diverged:
      Methylation of L1 and GAPDH sequences was strongly and moderately diminished,
      respectively, whereas methylation of satellite DNA was almost as high as that in
      stem cells. P19 embryonal carcinoma cells and D3 embryonic stem cells possessed
      methylation patterns similar to those of F9 stem cells. In immortalized cell
      lines with differentiated phenotypes derived from P19, methylation was diminished
      uniformly throughout the genome, but the overall level of methylation remained
      higher than that in terminally differentiated F9 cells. Treatment with the
      methylation inhibitor deoxyazacytidine halted the proliferation of 8a, P1, and F9
      cells and elicited marked changes in morphology. However, markers of
      differentiation were not induced in F9 cells. The finding that all immortalized
      differentiated derivatives of embryonal carcinoma cells retained a higher level
      of DNA methylation--at least in parts of their genomes--than did terminally
      differentiated cells may indicate a function of demethylation of DNA and of
      satellite sequences in particular in terminal differentiation of extraembryonic
      tissues.

PMID- 7507851
TI  - Keratinocyte growth factor and fibroblast growth factor action on DNA synthesis
      in rat and human hepatocytes: modulation by heparin.
AB  - Keratinocyte growth factor (KGF/FGF-7) is a member of the fibroblast growth
      factor (FGF) superfamily. Unlike other members of the family, the biological
      activity of KGF appears to be restricted to epithelial cells. Here we have tested
      the activity of KGF, acidic fibroblast growth factor (aFGF), and basic fibroblast
      growth factor (bFGF) on normal adult rat and human hepatocytes and their
      modulation by heparin. Although more modest than the growth response to epidermal
      growth factor (EGF) and hepatocyte growth factor (HGF), recombinant KGF enhanced
      DNA synthesis in rat hepatocytes by two- to threefold. This stimulation occurred
      in the absence of serum and of other exogenous growth factors. Addition of
      heparin inhibited the KGF response. Although basic FGF showed little activity on
      rat hepatocytes, acidic FGF stimulated DNA synthesis by approximately twofold and
      was substantially enhanced by heparin. In contrast to rat cells, human
      hepatocytes consistently failed to respond to KGF, aFGF, or bFGF with or without
      heparin, under conditions where EGF and HGF stimulated DNA synthesis up to
      sixfold. These results indicate that KGF is capable of acting as a complete
      mitogen for rat hepatocytes in culture and that the activity is consistent with
      expression by these cells of a type II FGF receptor subtype, the KGF receptor.
      These observations suggest that KGF/aFGF together with proteoglycans may help
      regulate rat but not human liver growth.

PMID- 7507853
TI  - In vitro angiogenic and proteolytic properties of bovine lymphatic endothelial
      cells.
AB  - The aim of the present study was to determine whether angiogenic cytokines, which
      induce neovascularization in the blood vascular system, might also be operative
      in the lymphatic system. In an assay of spontaneous in vitro angiogenesis,
      endothelial cells isolated from bovine lymphatic vessels retained their
      histotypic morphogenetic properties by forming capillary-like tubes. In a second
      assay, in which endothelial cells could be induced to invade a three-dimensional
      collagen gel within which they formed tube-like structures, lymphatic endothelial
      cells responded to basic fibroblast growth factor (bFGF) and vascular endothelial
      growth factor (VEGF) in a manner similar to what has previously been observed
      with endothelial cells derived from the blood vascular system. Finally, since
      angiogenesis is believed to require extracellular proteolytic activity, we
      investigated the effects of bFGF and VEGF on lymphatic endothelial cell
      proteolytic properties by focussing on the plasminogen activator (PA) system.
      bFGF and VEGF increased urokinase, urokinase receptor, and tissue-type PA
      expression. This was accompanied by an increase in PA inhibitor-1, which is
      thought to play an important permissive role in angiogenesis by protecting the
      extracellular matrix against excessive proteolytic degradation. Taken together,
      these results demonstrate that with respect to in vitro morphogenetic and
      proteolytic properties, lymphatic endothelial cells respond to the previously
      described angiogenic factors, bFGF and VEGF, in a manner very similar to what has
      been described for endothelial cells derived from the blood vascular system.

PMID- 7507852
TI  - SV40 T antigen inhibits expression of MyoD and myogenin, up-regulates Myf-5, but
      does not affect early expression of desmin or alpha 7 integrin during muscle
      development.
AB  - The terminal stage of myogenic development is marked by the cessation of
      replication, fusion, and expression of genes which encode the myofibrillar
      proteins. Prior to terminal differentiation one or more stages of myogenic
      development take place. Expression of alpha 7 integrin and desmin have been used
      as markers for these earlier stages of myogenesis. Both proteins are expressed in
      replicating secondary myoblasts prior to terminal differentiation and when these
      cells differentiate further, the expression of the alpha 7 integrin and desmin
      genes is up-regulated. To determine whether the stages of myogenesis which
      precede terminal development and the factors which regulate them are distinct,
      the expression of alpha 7 integrin and desmin was assayed in a variety of
      myogenic cell lines in which terminal differentiation was inhibited. L8E63 and C2
      myoblasts in which terminal differentiation was inhibited by SV40 large T
      antigen, adenovirus E1A protein, or ras and an L6 mutant whose terminal
      differentiation is sensitive to alpha-amanitin were studied. In all cases, when
      terminal myogenic differentiation is inhibited the basal levels of desmin and
      alpha 7 expression are not altered. Under these same conditions expression of the
      myogenic regulatory genes myogenin and MyoD also were inhibited whereas Myf-5
      persisted. These results indicate that expression of the early myogenic phenotype
      and terminal differentiation are discrete and independent stages of myogenesis
      and that different transcription factors likely regulate the expression of each
      stage. In contrast with myoblasts in cultures of newborn rat hindlimb cells and
      the C2 cell line, myogenic cells derived from C3H10T1/2 cells by treatment with 5
      azacytidine or by transfection with MyoD, Myf-5, or MRF4 do not express desmin as
      replicating myoblasts but do so upon terminal differentiation. This indicates
      that in vitro, terminal differentiation can proceed in the absence of the
      phenotypes that normally develop earlier and that the conversion of 10T1/2 cells
      to myogenic cells can bypass developmental stages which normally occur in vivo.
      These results are discussed in the context of a model of the myogenic lineage
      that is based on the expression of desmin.

PMID- 7507854
TI  - Thyroid cell spreading and focal adhesion formation depend upon protein tyrosine
      phosphorylation and actin microfilaments.
AB  - Adhesion to proteins of the extracellular matrix exerts a profound influence upon
      cell function and behavior. Similar adhesive interactions mediate the spreading
      of cultured cells upon artificial substrata. Recently we observed that
      thyrotropin (TSH) and intercellular contact regulated thyroid cell-substrate
      adhesion to inhibit cell spreading, but not initial attachment. This is a
      mechanism which preserves thyroid follicular differentiation in culture. In the
      present study we have investigated the role of cytoplasmic components in
      mediating thyroid cell adhesion to collagen. The earliest change associated with
      cell spreading was the accumulation of vinculin and phosphotyrosine in developing
      focal adhesions, which was followed by stress fiber and microtubule assembly.
      Genistein, an inhibitor of tyrosine kinases, and cytochalasin B inhibited cell
      spreading and focal adhesion formation without affecting initial attachment to
      substrate. In contrast microtubule disorganization by colchicine did not alter
      any parameter of thyroid cell-substrate adhesion. These observations indicate
      that protein tyrosine phosphorylation and dynamic microfilament integrity are
      essential for attached thyroid cells to spread upon substrate. They are therefore
      potential intracellular loci at which TSH and intercellular contact may regulate
      cell adhesion to extracellular matrix and influence thyroid cell behavior.

PMID- 7507855
TI  - Expression of hepatocyte growth factor is up-regulated through activation of a
      cAMP-mediated pathway.
AB  - Hepatocyte growth factor (HGF) is a multifunctional cytokine with mitogenic,
      motogenic, morphogenic, and tumor-suppressing activities. Despite the broad
      spectrum of its biological activities, HGF is most likely the physiological
      hepatotrophic factor that triggers or modulates liver regeneration. Regulatory
      mechanisms for HGF production are crucial for understanding the control of liver
      regeneration. We previously reported that HGF production by human skin
      fibroblasts is stimulated by a protein kinase C (PKC)-mediated pathway. We
      determined here whether gene expression and production of HGF in human skin
      fibroblasts can be induced via activation of a cAMP-mediated pathway. HGF
      secretion by the cells was markedly stimulated by the cAMP-elevating agents,
      forskolin, cholera toxin, prostaglandin E2 (PGE2), and 3-isobutyl-1
      methylxanthine, as well as by the membrane-permeable cAMP analogues, 8-bromo-cAMP
      and dibutyryl cAMP. The dose-response curves of induction of HGF secretion by
      cholera toxin and forskolin were nearly parallel with those of the intracellular
      cAMP levels. HGF mRNA levels did not significantly increase at 5 and 10 h, but
      increased considerably 15 h or more after the addition of cholera toxin.
      Forskolin, 8-bromo-cAMP, and PGE2 also caused appreciable up-regulation of HGF
      gene expression with a similar time course. Although human skin fibroblasts of
      various origins secreted variable amounts of HGF, the cAMP-elevating agents and
      the cAMP analogues caused a very marked increase in HGF production in all of
      them. The agents also enhanced highly active HGF secretion by MRC-5 human
      embryonic lung fibroblasts. Dexamethasone and transforming growth factor-beta 1,
      which inhibit PKC-mediated HGF secretion, down-regulated HGF mRNA expression and
      HGF production in the cells treated with the cAMP-elevating agents and the cAMP
      analogues. These results indicate that HGF expression in human skin fibroblasts
      is stimulated by activation of a cAMP-mediated pathway.

PMID- 7507856
TI  - Coordinate regulation of Steel factor, its receptor (Kit), and cytoadhesion
      molecule (ICAM-1 and ELAM-1) mRNA expression in human vascular endothelial cells
      of differing origins.
AB  - Endothelial cells (EC) are a major component of the bone marrow and peripheral
      vasculature microenvironments and contribute to the regulation of hematopoiesis.
      Human EC cultured from umbilical vein (HUVEC) and adult aorta (HAEC) were
      compared to determine differences in levels of the multipotent cytokine, Steel
      factor (SLF), its receptor (Kit), intercellular adhesion molecule-1 (ICAM-1), and
      endothelial leukocyte adhesion molecule-1 (ELAM-1) before and after stimulation
      with human interleukin-1 beta (hIL-1 beta), human tumor necrosis factor-alpha
      (hTNF-alpha), recombinant human (rh) SLF, phorbol 12-myristate 13-acetate (PMA),
      or calcium ionophore (A23187). HUVEC expressed four-fold higher basal levels of
      Kit and three-fold higher basal levels of SLF transcripts than HAEC. In contrast,
      the basal level of ICAM-1 mRNA was four-fold lower in HUVEC than in HAEC. These
      differences in expression persisted following activation. All five agonists
      downregulated Kit mRNA levels by 50 to 80%, but there remained a three-fold
      higher level of expression in HUVEC compared to HAEC. While SLF mRNA expression
      was increased four-fold by IL-1 beta or TNF-alpha and 50-fold by PMA or A23187,
      there was still a two-fold higher level in HUVEC than in HAEC. Similarly,
      production of cell-associated SLF was induced two-fold above basal level by PMA
      in HUVEC and HAEC, with HUVEC producing two-fold more than HAEC before and after
      stimulation. Production of soluble SLF was also increased six-fold in HUVEC and
      HAEC by PMA, but the HAEC produced slightly more than the HUVEC. Expression of
      ICAM-1 mRNA was increased 11-fold in activated HUVEC and HAEC, but the induced
      levels of both ICAM-1 and ELAM-1 mRNA were three-fold lower in HUVEC. The time
      course of SLF mRNA upregulation and Kit mRNA downregulation paralleled the
      upregulation of both cytoadhesion molecules. Differences between HUVEC and HAEC
      may be related to their vascular sources, but also suggest that disparate
      regulation of SLF, Kit, ICAM-1, and ELAM-1 expression could indicate a
      predisposition of neonatal EC toward impaired cytokine signal transmission.

PMID- 7507857
TI  - c-kit is expressed by primitive human hematopoietic cells that give rise to
      colony-forming cells in stroma-dependent or cytokine-supplemented culture.
AB  - Using monoclonal antibody (MAB) YB5.B8, we have examined the expression of the c
      kit protein, the receptor for the hematopoietic cytokine stem cell factor (SCF),
      on primitive hematopoietic cells. Bone marrow mononuclear cells (BMMNC) enriched
      for immature cells by differential agglutination using the lectin soybean
      agglutinin (SBA) were subjected to multiparameter fluorescence activated cell
      sorting (FACS) based on light-scattering properties, the expression of the c-kit
      protein and the CD34 antigen, and the retention of the vital fluorescent dye,
      Rhodamine 123 (Rh123). Sorted populations were assayed for their content of
      directly clonogenic progenitor cells (colony-forming units-granulocyte/macrophage
      [CFU-GM], burst-forming units-erythroid [BFU-E], and multipotential colony
      forming units [CFU-Mix]) and for the presence of more primitive progenitor cells
      ("pre-CFU"). The latter were assayed by (1) their ability to initiate and sustain
      hematopoiesis in a standard stromal cell-dependent culture system and (2) their
      capacity for de novo generation of clonogenic progenitors in response to a
      combination of six recombinant hematopoietic cytokines in a stroma-independent
      suspension culture assay. A mean of 76% of CD34+ cells were found to coexpress c
      kit. The majority of directly clonogenic cells (98% of CFU-GM, 98% of CFU-Mix,
      and 85% of BFU-E) were found in the CD34+c-kit+ fraction. Similarly, all pre-CFU
      were recovered in the CD34+c-kit+Rh123dull fraction, irrespective of whether the
      cells were maintained on marrow stromal cells or in cytokine-supplemented liquid
      culture. A mean of 87% (range 70-100%) of the CD34+Rh123dull cells also expressed
      c-kit. Since SCF has been reported to act as a growth factor for early lymphoid
      cells as well as myeloid cells, we looked for coexpression of c-kit and early
      lymphoid markers in the CD34+ population by multiparameter flow cytometry.
      Coexpression of c-kit on a minority of cells with markers of B or T lineages was
      observed. The majority of early lymphoid cells, however, appeared to lack c-kit
      expression. This was confirmed by the finding that only 4% of c-kit+CD34+ cells
      showed terminal deoxynucleotidyl transferase (TdT) activity, compared with 25% of
      the c-kit-CD34+ cells.

PMID- 7507858
TI  - Selection and characterization of early hematopoietic progenitors using an anti
      CD71/S06 immunotoxin.
AB  - Most recently reported methods to select early hematopoietic cells basically rely
      on the depletion of committed progenitors. This task is generally accomplished by
      laborious procedures, which are sometimes difficult to reproduce. To simplify the
      selection method, we took advantage of the expression of the transferrin receptor
      (CD71) by proliferating committed progenitors and the lack of CD71 on noncycling
      immature progenitors. A monoclonal antibody (MAB) reactive with CD71 has been
      conjugated to the Saponaria officinalis seed ribosome-inactivating protein (SO6).
      The immunotoxin (IT) complex was used at increasing concentrations on normal non
      phagocytizing bone marrow cells. A complete and reproducible killing effect on
      myeloid (colony-forming unit-granulocyte/macrophage [CFU-GM]) and erythroid
      (burst-forming unit-erythroid [BFU-E]) progenitors was observed for IT
      concentrations of 1 x 10(-7) M. Unconjugated SO6 or anti-CD71 MAB had no effect
      on cell growth and viability. IT-resistant cells were able to generate CFU-GM
      after 7, 14, and 21 days of suspension culture in the presence of 5637 CM.
      Maximal CFU-GM values were obtained at day 21 and nearly approached the
      pretreatment values (mean 2587 vs. 3877 CFU-GM/mL). Growth factor enhancement of
      CFU-GM yield was obtained only by stem cell factor (SCF) at day 7; SCF, as well
      as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3
      (IL-3), had an enhancing effect at days 14 and 21. IT toxicity on highly immature
      progenitors was ruled out by evaluating the growth of long-term culture
      initiating cells (LTC-IC) from IT-treated cultures. LTC-IC frequency was found to
      be 1 out of 1506 seeded cells, which is within the range of normal untreated BM
      cells. In conclusion, anti-CD71 IT allows a simple and complete depletion of
      committed progenitors while sparing immature hematopoietic cells. The high CD71
      expression by leukemic cells makes the procedure potentially suitable for in
      vitro purging.

PMID- 7507859
TI  - Sl/Sld hematopoietic progenitors are deficient in situ.
AB  - The hematopoietic microenvironment in Steel mutant mice does not support
      erythropoiesis, megakaryocytopoiesis, or mast cell generation. The question of
      whether Steel hematopoietic progenitors are present in normal numbers has never
      been convincingly addressed. In this report, Sl/Sld marrow cells were assessed
      for long-term competitive repopulation ability in vivo and for short-term growth
      in vitro. In vivo repopulation assays indicate that the Sl/Sld progenitors are at
      a distinct disadvantage when they compete against congenic genetically marked +/+
      cells in a +/+ host. On the other hand, the Steel erythroid colony-forming cells
      (CFU-E) respond normally to erythropoietin (Epo) in vitro and are present at
      normal frequency. Because the Steel marrow is less cellular than normal marrow,
      the absolute number of CFU-E is decreased. Results suggest that the absence of
      membrane-bound Steel factor in the mutant donor has a direct effect on Steel
      hematopoietic progenitors, which is not alleviated during growth for over 6
      months in a normal microenvironment. The anomaly does not seem to directly affect
      the frequency of more mature adult erythroid progenitors.

PMID- 7507860
TI  - Hematopoietic cytokines enhance survival of SCID mice undergoing high-dose
      irradiation.
AB  - We have investigated the effect of hematopoietic cytokines on the survival of
      severe combined immune-deficient (SCID) mice that received a high dose of
      radiation. In this study, female SCID mice were irradiated at doses ranging from
      500 to 600 cGy and then transplanted with 2 x 10(6) male Balb/c marrow cells.
      Groups of transplant recipients received stem cell factor (SCF), interleukin-1
      (IL-1), and IL-3, alone or in combination, once daily for 5 days immediately
      after irradiation. Control posttransplant SCID recipients did not survive more
      than 2 weeks after irradiation with the dose over 500 cGy. SCF alone did not
      enhance survival, and treatment with IL-1 or IL-3 had very limited capacity to
      improve survival. IL-1 plus IL-3 has some radioprotective effect on SCID
      recipients, but the strongest synergistic radioprotective effect was observed in
      mice treated with a combination of SCF, IL-1, and IL-3. These mice survived for
      more than 4 months after an irradiation dose up to 600 cGy. We also examined the
      origin of hematopoietic stem cells in transplant recipients. Bone marrow cells
      were obtained from the SCID mice treated with a combination of cytokines at 2 and
      4 months after transplant with male Balb/c marrow cells and irradiation with 600
      cGy. These marrow cells were then transplanted into secondary lethally irradiated
      female Balb/c recipients. Twelve-day spleen colonies (CFU-S) were analyzed by
      amplification of the Y-chromosome sequence of the sex-determining region by
      polymerase chain reaction (PCR). All spleen colonies were of donor origin,
      indicating that the SCID recipients were fully reconstituted by donor cells. The
      results suggest that SCF, synergistic with IL-1 and IL-3, protects SCID mice from
      lethal doses of radiation and allows complete long-term engraftment of SCID
      recipients.

PMID- 7507861
TI  - Identification of cytidine deaminase as inhibitor of granulocyte-macrophage
      colony formation.
AB  - Mature human blood granulocytes produce regulatory factors that inhibit colony
      formation by human and murine granulocyte-macrophage colony-forming cells (GM
      CFC). The inhibition of GM-CFC by granulocyte extract (GRE) was strongly enhanced
      by the addition of thymidine (3 to 6 x 10(-5) M for human cells) and by the
      presence of fetal calf serum (FCS) in the growth medium. Deoxycytidine and
      deoxyuridine produced effects similar to those of thymidine, but at higher
      concentrations (2 to 4 x 10(-4) M). It was further observed that GRE prevented
      the antiproliferative effects of cytosine arabinoside (Ara-C) and
      azadeoxycytidine, suggesting that GRE contained cytidine deaminase (CDD)
      activity, since CDD is known to abolish the effects of these nucleoside analogs.
      Accordingly, the GRE was tested for and shown to contain an enzymatic activity
      that converted deoxycytidine to deoxyuridine, confirming the presence of CDD
      activity in GRE. The GM-CFC inhibition factor was found to copurify with CDD
      activity during three succeeding chromatographic separations, indicating that CDD
      was indeed the inhibiting factor itself. This conclusion was further
      substantiated by gel filtration experiments demonstrating a molecular weight (MW)
      of approximately 50 kd, which corresponds to the MW previously published for CDD
      activity. Furthermore, addition of tetrahydrouridine (THU), a known specific
      inhibitor of CDD, abolished the suppressive effect of GRE on GM-CFC, which
      independently confirmed the identification of CDD as an inhibitor of GM-CFC. The
      growth-regulating property of CDD could be explained by depletion of
      deoxycytidine nucleotides necessary for DNA synthesis or by a direct effect of
      CDD binding to specific receptors on progenitor cells.

PMID- 7507862
TI  - Evaluation of the in vitro behavior of phenotypically defined populations of
      umbilical cord blood hematopoietic progenitor cells.
AB  - Umbilical cord blood (CB) has been identified as a potential source of
      hematopoietic stem cells suitable for clinical transplantation. We used long-term
      cord blood cultures (LTCBC) to evaluate the hematopoietic potential of
      populations of umbilical CB cells phenotypically defined and isolated by flow
      cytometry. LTCBC initiated with CD34+HLA-DR+ and CD34+HLA-DR- CB cells were
      examined over a period of 8 weeks for the production of assayable burst-forming
      units-erythroid (BFU-E), colony-forming units-granulocyte/macrophage (CFU-GM),
      and colony-forming units-mixed (CFU-GEMM) in response to repeated additions of
      stem cell factor (SCF), interleukin-3 (IL-3), IL-6, and either erythropoietin
      (Epo) or granulocyte-macrophage colony-stimulating factor (GM-CSF). The LTCBC
      initiating cell (LTCBC-IC) appeared to be present among CD34+HLA-DR+ cells, in
      contrast to our previous findings in adult bone marrow (BM), where the long-term
      culture initiating cells were shown to be CD34+HLA-DR-. In addition, production
      of BFU-E, CFU-GM, and CFU-GEMM in CB CD34+HLA-DR+ cells displaying low uptake of
      the supravital dye rhodamine 123 (Rh123) exceeded those detected in the fraction
      of cells with high uptake of Rh123. Furthermore, on day 21 of LTCBC, the
      production of the high proliferative potential colony-forming units (HPP-CFC) by
      CB CD34+HLA-DR+Rh123dull cells was five-fold greater than that detected in
      cultures initiated with their Rh123bright counterparts. Collectively, these data
      show that, contrary to what has been documented in adult human BM, LTCBC-IC and
      presumably CB cells capable of in vivo engraftment reside in the CD34+HLA
      DR+Rh123dull fraction of CB. Although the functional significance of these
      differences between the in vitro behavior of phenotypically defined populations
      of CB and BM remains to be determined, these findings constitute an objective
      parameter with which the suitability of CB for clinical transplantation may be
      assessed.

PMID- 7507863
TI  - Connectivity of fetal neocortical block transplants in the excitotoxically
      ablated cortex of adult rats.
AB  - Fetal neocortical block grafts placed into newborn recipients are able to
      exchange axonal projections with the host central nervous system, as shown in
      several previous experiments. The present study examined the connectivity of
      fetal neocortical block transplants placed into the excitotoxically ablated
      cortex of adult rats. Young adult rats received injections of the excitotoxic
      amino acid N-methyl-D-aspartate into the sensorimotor cortex area 1 week prior to
      receiving a fetal (E14-15) neocortical transplant. Afferent and efferent
      connections of these grafts were examined 3-6 months after transplantation by
      injecting the transplants with the fluorescent retrograde tracers fast blue and
      diamidino yellow or with the anterograde tracer Phaseolus vulgaris
      leucoagglutinin. Retrogradely labeled neurons were observed within several host
      brain regions including the ipsilateral neocortex, several thalamic nuclei,
      subcortical areas such as claustrum and lateral hypothalamus, nucleus basalis,
      dorsal raphe nuclei and locus coeruleus. Fibers labeled with Phaseolus vulgaris
      leucoagglutinin were found extending throughout the transplants, but with rare
      exceptions fibers were not observed within the host brain. The experiments showed
      that neocortical block grafts placed into the excitotoxically ablated neocortex
      receive afferent input from areas in the host brain that normally innervate the
      sensorimotor cortex. The extensive Phaseolus vulgaris leucoagglutinin-positive
      axonal labeling found within the grafts demonstrated the ability of the grafted
      neurons to establish extensive intrinsic graft connections.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7507864
TI  - Effects of alpha thalassaemia and haemoglobin F (HbF) level on the clinical
      severity of sickle-cell anaemia.
AB  - Three clinical parameters - average steady-state haematocrit (ASSH), number of
      crises per year (Cr/Y), and number of transfusions per year (Tx/Y) - were
      evaluated in 52 patients with sickle-cell anaemia in relation to their foetal
      haemoglobin (HbF) levels. No correlation was observed between HbF and any of
      these parameters. A comparison of these three clinical parameters and the alpha
      globin gene status was also made in 28 of these patients. The relationships
      between (ASSH) or (Cr/Y) and alpha globin gene status were not significantly
      different (p > 0.05) but a significantly different value (p < 0.05) was observed
      between (Tx/Y) and the alpha globin gene status in these patients. It is
      concluded that, although HbF levels did not affect any of these parameters, alpha
      thalassaemia deletion significantly reduces the transfusion requirements of these
      patients.

PMID- 7507866
TI  - Detection of human leukocyte antigen class I messenger ribonucleic acid
      transcripts in human spermatozoa via reverse transcription-polymerase chain
      reaction.
AB  - OBJECTIVE: To determine by reverse transcription-polymerase chain reaction (PCR)
      whether human leukocyte antigen (HLA) class I messenger RNA (mRNA) is present in
      mature human spermatozoa. DESIGN: Mature human spermatozoa was isolated from
      donor semen using a swim-up technique. Total RNA was extracted via guanidinium
      isothiocyanate-cesium chloride ultracentrifugation. By the method previously
      validated in our laboratory, reverse transcription-PCR was performed using
      primers specific for HLA class I transcripts. Positive control cells included a
      choriocarcinoma cell line (JEG) and human fetal tissue. Transformed peripheral
      blood lymphocytes (PBL) were used as a negative control for somatic cellular
      contamination. RESULTS: Human spermatozoa were positive for HLA class I (-G and 
      B) mRNA by reverse transcription-PCR, consistent with the positive controls. We
      did not detect any mRNA for beta-actin, retinoblastoma (RB), CD4, or kappa light
      chain genes in the sperm complementary DNA samples, verifying that the class I
      mRNA detected was not due to somatic cellular contamination of the purified sperm
      samples. CONCLUSION: These experiments provide the first evidence that mRNA for
      HLA class I molecules are present in mature human spermatozoa. The physiological
      role of these transcripts is unknown at present. Further experiments
      characterizing the expression of HLA class I (-G and -B) mRNA in oocytes and
      preimplantation embryos are in progress.

PMID- 7507865
TI  - Effects of recombinant human stem cell factor (rh-SCF) on colony formation and
      long-term bone marrow cultures (LTBMC) in patients with myelodysplastic
      syndromes.
AB  - Stem cell factor (SCF), the ligand of the c-kit receptor, is a potent enhancing
      cytokine for haematopoietic cells in the presence of IL-3, GM-CSF and
      erythropoietin (Epo). In the clonogenic assays of 63 MDS patients, the addition
      of rh-SCF + GM-CSF and/or IL-3 induced a significant increase (p < 0.001) in the
      number and size of CFU-GM. Never reaching the levels of controls, this increase
      was seen in all FAB subtypes, but particularly in RA. There was no significant
      increase in cluster formation, even in RAEB or RAEBt. Rh-SCF (10 ng/ml) led to
      mean increases of up to 26 times in the number of Epo-dependent BFU-E colonies,
      particularly in RA (p < 0.001) and RAEB (p < 0.05). Individual responses varied
      widely (especially in RA) from no response to supranormal levels. Added to the
      weekly refeed of 37 MDS LTBMC, SCF (10 ng/ml) induced only a 7% mean increase in
      both cell output and the number of clonogenic cells recovered in the supernatant.
      Immunohistochemical examination of the supernatant showed significant increases
      in differentiating myeloid cells in all examined cases, and in erythroid cells in
      3 cases; blast cells increased in only 3 cases. These data suggest that rh-SCF is
      capable of at least partially reversing defective MDS myeloid haematopoiesis, and
      leads no overt risk of leukaemic transformation. Its potent effect on erythroid
      cells is encouraging for future clinical applications in patients, particularly
      if they are selected by means of in vitro tests.

PMID- 7507868
TI  - Intermediate filament proteins and epithelial differentiation in the embryonic
      ovary of the rat.
AB  - The development and sexual differentiation of gonads in female rat embryos and
      fetuses between the ages of 11 and 17 days was studied by immunocytochemical
      analysis of intermediate filament proteins and laminin by light and electron
      microscopy. In the 11-day-old pregonadal embryo, the surface epithelial cells in
      the ventral cortex of the mesonephros contained desmin but not cytokeratin or
      vimentin. The development of the gonad began on the following day by
      proliferative growth of the mesonephric surface cells, which like the
      subepithelial cells soon expressed vimentin in addition to desmin. The
      differentiation continued by formation of separate epithelial cell clusters,
      which joined into cords, irregular in shape and size. Desmin disappeared from the
      cord cells and cytokeratins appeared while vimentin remained in all somatic cell
      types. Desmin was especially abundant in some stromal cells adjacent to the
      epithelial tissues. After the segration of the basic ovarian tissues, vimentin
      and desmin decreased and cytokeratins appeared in the surface epithelial cells.
      New changes in cytokeratin expression appeared with the differentiation of the
      embryonic cords in a sex-specific manner with gradual decrease of reactivity for
      cytokeratin 18. No immunoreaction to the neurofilament proteins was found at the
      present ages, and the germ cells were negative for intermediate filaments. The
      results show that desmin is expressed in several primitive ovarian and
      mesonephric cells even though they are not myogenic.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7507867
TI  - Immunophenotypic properties and estrogen dependency of budding cell structures in
      the developing mouse mammary gland.
AB  - The initial phase of growth of the parenchymal component of the mouse mammary
      gland is ductal clongation, which is mainly accomplished by proliferating cells
      in a specialized structure termed end bud. End buds are composed of multiple
      layers of epithelial cells (so called body cells) which are capped by a single
      layer of morphologically unique cells termed cap cells. We sought to examine the
      interrelationship between cap cells and other epithelial cell subclasses using a
      variety of antibodies to different keratin proteins and also antibodies to
      vimentin, actin and collagen IV. An extensive immunohistochemical
      characterization of the epithelial components of the developing and
      differentiating mammary gland demonstrated that cap cells were devoid of any
      immunohistochemically-detectable keratins but were positive for collagen IV. In
      contrast, the majority of cells in the end bud along with the luminal epithelial
      and myoepithelial cells were keratin positive. The body cells of the end bud were
      the only cells which were positive for antibody to keratin 6, a keratin which
      previously has been reported to be expressed in proliferating mammary epithelial
      cells. In addition, estrogen receptor was localized only to epithelial cells of
      ducts, alvcoli and body cells of end buds, but not to cap cells or myoepithelial
      cells. We interpret these results to suggest that cap cells are not totpotent
      stem cells but rather cells specialized in paving the way for ductal elongation
      as well as serving as precursors to myoepithelial cells.

PMID- 7507869
TI  - Molecular characterization of the body site-specific human epidermal cytokeratin
      9: cDNA cloning, amino acid sequence, and tissue specificity of gene expression.
AB  - Differentiation of human plantar and palmar epidermis is characterized by the
      suprabasal synthesis of a major special intermediate-sized filament (IF) protein,
      the type I (acidic) cytokeratin 9 (CK 9). Using partial amino acid (aa) sequence
      information obtained by direct Edman sequencing of peptides resulting from
      proteolytic digestion of purified CK 9, we synthesized several redundant primers
      by 'back-translation'. Amplification by polymerase chain reaction (PCR) of cDNAs
      obtained by reverse transcription of mRNAs from human foot sole epidermis,
      including 5'-primer extension, resulted in multiple overlapping cDNA clones, from
      which the complete cDNA (2353 bp) could be constructed. This cDNA encoded the CK
      9 polypeptide with a calculated molecular weight of 61,987 and an isoelectric
      point at about pH 5.0. The aa sequence deduced from cDNA was verified in several
      parts by comparison with the peptide sequences and showed the typical structure
      of type I CKs, with a head (153 aa), and alpha-helical coiled-coil-forming rod
      (306 aa), and a tail (163 aa) domain. The protein displayed the highest homology
      to human CK 10, not only in the highly conserved rod domain but also in large
      parts of the head and the tail domains. On the other hand, the aa sequence
      revealed some remarkable differences from CK 10 and other CKs, even in the most
      conserved segments of the rod domain. The nuclease digestion pattern seen on
      Southern blot analysis of human genomic DNA indicated the existence of a unique
      CK 9 gene. Using CK 9-specific riboprobes for hybridization on Northern blots of
      RNAs from various epithelia, a mRNA of about 2.4 kb in length could be identified
      only in foot sole epidermis, and a weaker cross-hybridization signal was seen in
      RNA from bovine heel pad epidermis at about 2.0 kb. A large number of tissues and
      cell cultures were examined by PCR of mRNA-derived cDNAs, using CK 9-specific
      primers. But even with this very sensitive signal amplification, only
      palmar/plantar epidermis was found positive. By in situ hybridization and
      immunolocalization we further showed that CK 9 is only expressed in the
      suprabasal cell layers of this special epidermal tissue. We discuss the molecular
      properties of CK 9 and its cell type- and body site-specific expression in
      relation to the special differentiation of palmar/plantar epidermis and to
      diseases specific for this body site.

PMID- 7507870
TI  - Noncoordinated responses of branched-chain alpha-ketoacid dehydrogenase subunit
      genes to dietary protein.
AB  - The response of the murine genes encoding the subunits of branched-chain alpha
      ketoacid dehydrogenase complex (BCKAD) to changes in dietary protein was
      determined. Steady-state RNA levels for two of the subunits, E1 beta and E2,
      decreased by two- to four-fold in the livers of mice fed 0% protein isocaloric
      diets compared to the levels observed in mice fed standard (23%) or high (50%)
      protein isocaloric diets. In contrast, the levels of RNA encoding the E1 alpha
      subunit did not change significantly in response to these dietary protein
      changes. The hepatic decreases in E1 beta and E2 RNA associated with 0% protein
      isocaloric diets were reversible, with prompt return to baseline levels following
      48 hours of 50% protein isocaloric diets ad libitum. In kidney, no significant
      changes in the RNAs encoding any of the three BCKAD subunits were observed in
      response to changes in dietary protein. Studies of RNA variations associated with
      growth and development in several murine tissues, including liver and kidney,
      demonstrated coordinated changes between all subunits. Similar coordinated
      changes were observed during 3T3-L1 adipocyte differentiation. These studies
      suggest that the responses of the BCKAD subunit genes to alterations in dietary
      protein are noncoordinated and tissue-specific, in contrast to the coordinated
      changes observed during growth and/or differentiation. The differences in BCKAD
      subunit RNA levels observed under varying nutritional and developmental
      conditions suggest that multiple regulatory mechanisms modulate BCKAD subunit
      expression.

PMID- 7507871
TI  - Nutritional regulation of growth hormone receptor gene expression.
AB  - The role of energy intake in regulating growth hormone receptor (GHR) gene
      expression has been assessed in young growing pigs living at thermal neutrality
      (26 degrees C) for a 4-wk period. To determine the importance of altering
      metabolic demand while maintaining food intake constant, littermates were also
      studied in a cold environment (10 degrees C). Results were tissue-specific: the
      level of GHR mRNA per unit total RNA in liver was greater on high than low (high
      = 2 x low) food intake (P < 0.001), whereas in muscle it was elevated on the low
      compared with the high intake diet (P < 0.02) and also at 10 degrees C compared
      with 26 degrees C (P < 0.04). When results for GHR mRNA were expressed per unit
      weight of tissue, only the effects of diet on liver and temperature on muscle
      remained significant. The changes in hepatic GHR mRNA may have been driven in
      part by nutritionally induced changes in thyroid status, because both plasma
      3,5,3'-triiodothyronine concentration and liver 5'-deiodinase activity were
      greater on the high than the low intake diet (P < 0.001). Levels of liver GHR
      mRNA probably had a direct influence on growth of the animals, as they were
      positively correlated with plasma IGF-I and growth rate (P < 0.001), whereas
      muscle GHR mRNA may have had a metabolic role when energy supplies were limited.

PMID- 7507872
TI  - Ionizing radiation reduces neurally evoked electrolyte transport in rat ileum
      through a mast cell-dependent mechanism.
AB  - BACKGROUND/AIMS: Mechanisms of neuroimmune regulation of intestinal electrolyte
      transport under pathophysiological conditions are unclear. This study
      investigated the effect of ionizing radiation on ileal electrolyte transport.
      METHODS: Rats were exposed to 10 Gy gamma-radiation and were killed 2, 24, and 48
      hours later. Ileal segments were either mounted in Ussing chambers and exposed to
      electrical field stimulation, prostaglandin E2, leukotriene D4, or theophylline,
      or they were assayed for biochemical indices of inflammation. Other segments were
      processed for routine histological screening, mast cell counts, or
      immunohistochemical analysis of the distribution of vasoactive intestinal
      polypeptide or substance P immunoreactivity. RESULTS: Basal short-circuit current
      was unchanged 2, 24, or 48 hours postirradiation. However, there was a reduction
      of tissue responsiveness to electrical field stimulation, prostaglandin E2, and
      theophylline but not to leukotriene D4. Decreased responsiveness at 2-hours
      postirradiation was blocked by pretreatment with the H1 antagonist pyrilamine.
      Tissue myeloperoxidase activity and 5-hydroxytryptamine content were not altered
      postirradiation, but tissue histamine and mucosal mast cells were significantly
      reduced at 24 and 48 hours. There were no significant changes in villus-crypt
      architecture until 48 hours postirradiation. There was no significant alteration
      in the distribution of immunoreactive vasoactive intestinal polypeptide or
      substance P. CONCLUSIONS: Ionizing radiation reduced the transport response to
      neural stimulation. The effect correlated temporally with decreased mast cells
      and histamine, suggesting a functional role for previously reported mast cell
      nerve interactions.

PMID- 7507873
TI  - A glucocorticoid prodrug facilitates normal mucosal function in rat colitis
      without adrenal suppression.
AB  - BACKGROUND/AIMS: Glucocorticoids remain the foundation of therapy for acute
      ulcerative colitis despite systemic side effects that limit their use. Prodrugs
      that selectively deliver glucocorticoids to the colon may lower the required dose
      and side effects. The aim of this study was to assess the efficacy of a newly
      synthesized glucocorticoid-dextran prodrug. METHODS: Novel glucocorticoid-dextran
      prodrug conjugates in which dexamethasone and methylprednisolone were attached to
      dextran were synthesized using the dicarboxylic acid linkers, succinate and
      glutarate. The efficacy of the dextran prodrug conjugates and their free
      glucocorticoids was tested in an acetic acid-induced model of colitis. Repair of
      the colitis and mucosal function was assessed by measuring net intestinal fluid
      absorption, macroscopic ulceration, and myeloperoxidase activity. Glucocorticoid
      toxicity was evaluated by measuring plasma adrenocorticotropic hormone and serum
      corticosterone levels. RESULTS: The prodrug dexamethasone-succinate-dextran was
      nine times more potent and dexamethasone-glutarate-dextran three times more
      potent than free dexamethasone in accelerating mucosal repair. Similarly,
      methylprednisolone-succinate-dextran was four times more potent than free
      methylprednisolone. The dextran prodrug conjugates affected adrenocorticotropic
      hormone and corticosterone levels only at the highest doses in contrast to free
      dexamethasone and methylprednisolone, which caused marked adrenal suppression at
      all doses. CONCLUSIONS: The results show that recently synthesized glucocorticoid
      dextran prodrug conjugates can be administered orally to facilitate mucosal
      repair in rat colitis without adrenosuppression.

PMID- 7507875
TI  - Buchnera aphidicola (a prokaryotic endosymbiont of aphids) contains a putative
      16S rRNA operon unlinked to the 23S rRNA-encoding gene: sequence determination,
      and promoter and terminator analysis.
AB  - The aphid Schizaphis graminum is dependent on an association with Buchnera
      aphidicola, an eubacterial endosymbiont located in specialized host cells. Past
      studies have indicated that Escherichia coli is the closest known relative of the
      endosymbiont which has many genetic attributes of free-living bacteria. In order
      to obtain information on the properties of highly expressed genes, we have chosen
      for study the single-copy rrs (gene encoding 16S rRNA) of B. aphidicola. A 4.4-kb
      DNA fragment was cloned into E. coli and the nucleotide (nt) sequence determined.
      Several ORFs were identified; the order of genes was argS-rrs-ORF1-rnh-dnaQ.
      ArgS, RNase H and DnaQ had 36-57% amino acid (aa) identity to the homologous
      proteins of E. coli. B. aphidicola rrs appears to be part of an operon consisting
      of a putative promoter, rrs and two inverted repeats resembling Rho-independent
      terminators. Comparisons of the sequences of argS-rrn DNA fragments from
      endosymbionts of six additional aphid species indicated conservation of sequences
      corresponding to a single -35 (TTGACA) and -10 (TGTAAT) promoter region, as well
      as boxA (sequence involved in antitermination) and boxC. The B. aphidicola argS
      rrn DNA fragments from endosymbionts from seven species of aphids had promoter
      activities in E. coli which ranged from 6 to 135% of that observed with a
      comparable DNA fragment of E. coli rrnB. Similarly, the putative B. aphidicola
      terminator was functional in E. coli. In most eubacteria, the rRNA-encoding genes
      are arranged in the order, 16S, 23S, 5S, and are part of a single
      operon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507874
TI  - Substance P attenuates gastric mucosal hyperemia after stimulation of sensory
      neurons in the rat stomach.
AB  - BACKGROUND/AIMS: Sensory neurons in the stomach mucosa are closely apposed to
      mast cells and blood vessels. Mucosal hyperemia, after exposure to capsaicin, is
      mediated by calcitonin gene-related peptide (CGRP) from these neurons, which also
      contain substance P (SP). However, the role of this peptide in blood flow
      regulation remains unclear. Therefore, this study examines the effect of SP on
      capsaicin-induced mucosal hyperemia and mast cells. METHODS: Gastric mucosal
      blood flow was measured with laser Doppler flow velocimetry in chambered rat
      stomachs. SP, aprotinin (serine protease inhibitor), and ketotifen (mast cell
      stabilizer) were infused into the splenic artery of rats. Mast cells were counted
      by microscopy. RESULTS: Mucosal exposure to capsaicin (640 mumol/L) evoked a 70%
      increase in mucosal blood flow, which was abolished by SP, whereas aprotinin
      infused with SP and pretreatment with ketotifen before SP infusion restored the
      hyperemic response. Morphometry showed that ketotifen inhibited mast cell
      degranulation in SP-treated animals. Preservation of mast cells in SP-treated
      rats was linearly correlated to increased mucosal blood flow after exposure to
      capsaicin. CONCLUSIONS: These data suggest that SP participates in regulation of
      gastric mucosal blood flow by activation of mast cells most likely by releasing
      proteases from mast cells that cleave and inactivate CGRP.

PMID- 7507877
TI  - A gene expression vector useful for protein purification and studies of protein
      protein interaction.
AB  - This report describes the development of a gene expression vector that adds three
      features to the C-terminus of the putative synthesized protein: (1) a protein
      kinase A recognition domain allowing the protein to be radio-labeled in vitro,
      (2) an epitope marker for immunocharacterization of the protein with a commercial
      monoclonal antibody, and (3) a (His)6 block facilitating purification of the
      protein by metal chelating affinity chromatography. These features make it
      convenient to perform biochemical and functional analysis of the protein of
      interest.

PMID- 7507876
TI  - An interferon-induced Mx protein: cDNA sequence and high-level expression in the
      endometrium of pregnant sheep.
AB  - We have cloned a 2.4-kb cDNA containing the complete coding sequence of ovine Mx
      from a lambda ZAP library constructed using RNA from the endometrium of a normal
      sheep on day 16 of pregnancy. Ovine Mx shows 80% similarity to human MxA. Human
      and mouse Mx are type-1 interferon (IFN)-induced genes that have previously been
      shown to confer resistance to influenza virus. The ovine Mx cDNA contains an open
      reading frame of 1962 nucleotides (nt) coding for a 653-amino-acid (aa) protein.
      The deduced translated sequence has consensus GTP-binding sites and similarity to
      the human MxA sequence (RKFLKERLARL) that has been shown to be essential for
      resistance against vesicular stomatitis virus (VSV). The presence of Mx mRNA was
      investigated by Northern blot analysis in the endometrium of non-pregnant sheep
      and between days 8 and 127 of pregnancy. Mx expression was detected at high
      levels between day 13 and day 20 of pregnancy. Furthermore, eightfold higher
      levels of Mx mRNA were detected in the pregnant versus the non-pregnant uterine
      horn in unilaterally pregnant sheep. Mx mRNA can be induced in sheep endometrium
      by ovine trophoblast interferon (IFN-tau).

PMID- 7507878
TI  - Interferon decreases serum lipid peroxidation products of hepatitis C patients.
AB  - Thiobarbituric acid reactive substances (TBARS) concentration in serum has been
      determined in healthy subjects and in patients suffering acute hepatitis and
      chronic cases of hepatitis C. Treatment with interferon of the chronic active
      hepatitis C patients, 5 x 10(6) U three times a week during 2 months, led in
      those patients whose SGPT activity normalized in serum, to a concomitant decrease
      in serum TBARS content. The possible theoretical involvement of peroxidation and
      antioxidants in this beneficial effect of interferon in hepatitis C patients is
      discussed. The results presented confirm the value of TBARS as laboratory test in
      the management of liver diseases and as a useful tool for the study of pathogenic
      and/or therapeutic mechanisms of this viral infection.

PMID- 7507879
TI  - Acquired growth hormone resistance in patients with hypercatabolism.
AB  - Sepsis, surgery and critical illness are associated with an increased catabolic
      rate, which if prolonged delays recovery and increases morbidity and mortality.
      There is evidence that changes in the GH/IGF-I axis are permissive to protein
      catabolism. Critically ill, septic patients have high basal levels of GH, low
      levels of IGF-I and its carrier binding protein IGFBP-3, high levels of an
      inhibitory binding protein, IGFBP-I, and increased serum protease activity which
      reduces the affinity of IGFBP-3 for IGF-I. Overall there is a reduction in the
      indirect IGF-I-mediated anabolic actions of GH and an increase in the direct
      catabolic actions of GH. These physiological changes may be adaptive when a sick
      patient is fasting; however, the availability of modern intensive care means that
      these changes are no longer an advantage. GH and IGF-I, in pharmacological doses,
      promote positive nitrogen balance, in both animal models and man. Preliminary
      studies with IGF-I in postsurgical patients suggest that it may provide a
      practical therapy. Future studies need to focus on outcome measures in relation
      to the use of GH and IGF-I as anabolic therapies.

PMID- 7507880
TI  - Effects of a chronic treatment with octreotide in patients with functionless
      pituitary adenomas.
AB  - The effects of a chronic treatment with octreotide were evaluated in 19 patients
      affected with functionless pituitary adenomas. Octreotide caused a significant
      decrease of GH and IGF-I levels in all the patients and no significant change in
      thyroid, adrenal and gonadal function. In contrast, during the therapy, the
      glucose response to an oral glucose tolerance test considerably increased and was
      delayed, while the insulin response decreased and was delayed. Serum alpha
      subunit (alpha-SU) was above normal in 10 of 16 patients in which this evaluation
      was performed: octreotide caused a significant decrease (p < 0.01) of alpha-SU
      levels in 6 of these 10 patients. Octreotide did not induce any significant
      change in visual fields except in 1 patient, who had a great improvement of
      visual perimetry and a decrease of alpha-SU levels but unmodified CT scan
      features. In our series of patients, octreotide was ineffective in reducing tumor
      mass. The efficacy of octreotide might rely on the presence of somatostatin
      receptors on adenoma-cell membranes. Therefore patients with functionless
      adenomas to be treated with octreotide might be identified with pituitary
      scintiscan using the recently available labeled 111In-octreotide.

PMID- 7507881
TI  - Immunohistochemical detection of granulocyte/macrophage colony-stimulating factor
      in Langerhans' cell histiocytosis.
AB  - Granulocyte/macrophage-colony stimulating factor (GM-CSF) induces in vitro
      activation of Langerhans' cells. The association of GM-CSF and tumour necrosis
      factor alpha (TNF alpha) induces the differentiation of Langerhans' cells from
      CD34 positive haematopoietic progenitors. Intradermal administration of
      recombinant GM-CSF is associated with local accumulation of Langerhans' cells. We
      investigated the presence of GM-CSF in tissue samples of 10 patients with
      Langerhans' cell histiocytosis. Four patients had skin involvement, three had
      bone and three had diffuse disease. Eight normal skin samples were analysed as
      controls. Immunohistochemistry was performed on frozen tissue samples with two
      specific monoclonal antibodies directed against two different epitopes of GM-CSF.
      We detected GM-CSF in all the histiocytosis tissue samples. The GM-CSF was
      detected within the cytoplasm of all the tumoral Langerhans' cells. We did not
      find GM-CSF in any other cell type. These results suggest that GM-CSF may be
      implicated in the pathogenesis of Langerhans' cell histiocytosis.

PMID- 7507883
TI  - Synthesis of antibodies against measles virus and myelin by in vitro stimulated B
      cells derived from patients with subacute sclerosing panencephalitis.
AB  - Subacute sclerosing panencephalitis (SSPE) patients carry persistent measles
      virus infection in the brain. Furthermore, the blood lymphocytes contain viral
      RNA. Lymphocytes derived from 6 SSPE patients were stimulated with Epstein-Barr
      virus (EBV). Production of antibodies against measles virus of the IgG isotype
      was detected in the supernatants of cell cultures of all patients, regardless of
      the disease's activity, duration or interferon therapy. In contrast, only some of
      these cell cultures also produced antibodies against myelin.

PMID- 7507882
TI  - A monoclonal antibody against carbohydrate moiety of rat gastric surface
      epithelial cell-derived mucin.
AB  - A monoclonal antibody (MAb), designated RGM11, was generated against mucin
      purified from the surface epithelial layer of rat gastric mucosa. RGM11 reacted
      with the purified mucin which had been attached to the ELISA well. This reaction
      was inhibited by the oxidation of the ELISA well with periodate, indicating the
      carbohydrate moiety of the mucin molecule to be the epitope of RGM11. Treatment
      of the ELISA well with galactose oxidase also reduced the reaction with this MAb,
      thus suggesting the peripheral galactose and/or N-acetylgalactosamine residues of
      the carbohydrate moiety of mucin are involved in the epitope structure.
      Histochemical observation indicated that this MAb was able to stain the formalin
      fixed-paraffin embedded sections of rat and was positive to the surface mucous
      cells of corpus and antral region of the stomach and the villus epithelium of the
      duodenal mucosa, but other organs and tissues of rat so far examined were all
      negative to this MAb. These results indicate that this newly established MAb,
      labelled RGM11, might be useful to estimate the physiological changes in gastric
      surface mucous cells and the role of surface epithelial cell derived mucus in the
      gastric mucosal defense mechanisms.

PMID- 7507884
TI  - The CD44 expressed on the earliest intrathymic precursor population functions as
      a thymus homing molecule but does not bind to hyaluronate.
AB  - A minute population of cells representing the earliest lymphoid-restricted
      precursor cells in the adult mouse thymus has been isolated recently in our
      laboratory. This population expresses low levels of CD4, very high levels of CD44
      and has a surface antigenic phenotype similar to that of bone marrow hemopoietic
      stem cells. To examine the role of CD44 on these cells, and to ascertain its
      ligand, we analysed the ability of the early thymic precursor cells to bind
      hyaluronate (HA) which functions as a cell adhesion molecule and a ligand for
      CD44. We also examined if anti-CD44 antibodies (clones IM7.8.1 and KM201) can
      block the thymic precursor activity. The majority of the thymic precursor cells
      did not show specific HA binding, indicating that HA is not the ligand for the
      CD44 molecules expressed on these precursor cells. HA and CD44 interactions are
      therefore unlikely to play a role in development of cells at this early
      intrathymic precursor stage. When the purified intrathymic precursor cells were
      incubated with anti-CD44 antibodies before intravenous transfer into recipients,
      very few progeny cells were detected in the thymus, although progeny were found
      in the spleen and lymph nodes. Coating the cells with other isotype-matched
      antibodies did not have this effect. However, when the same anti-CD44-coated
      cells were transferred directly into the recipient thymus, normal levels of
      progeny cells were detected in this organ. This suggests that the CD44 on the
      intrathymic precursor cells is a homing molecule, able to direct cells to the
      thymus but utilizing some ligand other than HA.

PMID- 7507885
TI  - Mutual antagonism between antigen- and lipopolysaccharide-induced antibody
      production.
AB  - B cells are induced to antibody production by antigens or by mitogens, such as
      lipopolysaccharide (LPS). We observed a mutually antagonistic relationship
      between activation through the antigen-receptor (AgR) and LPS-receptor (LPSR) in
      vitro. Prior exposure of B cells to AgR-ligating antibody prevented antibody
      forming cell (AFC) production induced by LPS, but not that induced by specific
      antigen (SRBC, TNP-Ficoll, or TNP-LPS). AFC production induced by antigen could
      be abrogated by concomitant exposure to LPS; the shutdown of the antigen-driven
      response was apparent when LPS-induced AFC were prevented by pre-exposure to
      antibody against the AgR. The ability of signaling through the AgR to inhibit
      antibody production stimulated by LPS was seen in DBA/2 and BALB/c mouse strains,
      and not in the New Zealand Black (NZB) strain. The results suggest that mutual
      antagonism is distinct from other forms of immune hyporesponsiveness, and that
      defects in antagonism may be a factor in the development of autoimmune disease.

PMID- 7507886
TI  - In vivo staining of oligodendroglia in the rabbit retina.
AB  - We have discovered that a strongly fluorescent dye, sulforhodamine 101, when
      injected intravitreally in vivo, very effectively stains a class of star-shaped
      cells in the innermost layers of the rabbit retina. The cells were strictly
      confined to the region containing medullated fibers and emitted dichotomously
      branching processes that ended up running some distance along the myelinated
      fibers. In favorable cases they could be seen to ensheath the fibers in a tube
      like fashion. No other retinal cells were stained. Shortly (hours) after the
      injection, the stain appeared in the cell cytoplasm, but it later became
      progressively more localized to intracellular granules. Most of the dye had
      disappeared after 2 days. Oligodendrocytes and astrocytes are the only cells
      known to be confined to the region of the medullated fibers in the rabbit retina,
      and hence the sulforhodamine 101-stained cells should be one of these two types.
      Sulforhodamine 101-stained cells were indistinguishable from oligodendrocytes
      identified by 2',3'-cyclic nucleotide phosphodiesterase (CNP)
      immunohistochemistry, and sequential staining showed them to be the same.
      Sulforhodamine 101-stained cells were microinjected with lucifer yellow after
      lightly fixing rabbit retinas with formaldehyde and were found to be
      indistinguishable from oligodendrocytes. Glial fibrillary acidic protein staining
      for astrocytes showed fiber bundles that to some extent were similar to the
      bundles stained by sulforhodamine 101, but at the level of individual fibers, it
      was impossible to establish any concordance. Sulforhodamine 101 thus appears to
      stain oligodendrocytes rather than astrocytes in the rabbit retina. A related
      dye, rhodamine 123, also stained rabbit oligodendrocytes, but with poor contrast
      because many other cells and structures were also stained.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7507887
TI  - Transplants of immature astrocytes promote axonal regeneration in the adult rat
      brain.
AB  - To study beneficial effects of immature astrocytes on axonal regeneration in the
      injured adult mammalian brain, we have stereotactically implanted cultured
      astrocytes from embryonic (E 14-16) rat cerebral cortex into the lesion site
      following transection of the postcommissural fornix. The spatio-temporal pattern
      of axonal degeneration and regrowth in the proximal fornix stump was investigated
      using wheat germ agglutinin-horseradish peroxidase tracing techniques and
      quantitative analysis of myelinated axon profiles. Transection of the
      postcommissural fornix tract caused disintegration of the axons in the distal
      stump as well as rapid and pronounced retrograde axonal degeneration up to 800
      1,200 microns proximal to the lesion site. While a small bundle of subicular
      fibers spontaneously extended to the lesion site within 4 weeks after injury,
      axonal regeneration was markedly stimulated in those animals that had received an
      astroglial implant. Following the former pathway, regenerating axons sprouted
      towards the implant but did not penetrate the graft. Instead, the axons elongated
      over the surface of the transplant, avoiding growth into the surrounding neuropil
      or into the distal fornix segment. In grafted animals we further observed a
      substantial increase in the number of myelinated axons of approximately 31.5% (at
      the level of 800 microns) and approximately 40% (at the 400 microns level)
      compared with the injured tract lacking a transplant. Our results indicate the
      capacity of juvenile astrocytes to stimulate axonal regeneration after injury of
      the post-commissural fornix tract in the adult rat brain. We further demonstrate
      myelination of the regenerated axons.

PMID- 7507888
TI  - Mimicry of a neutralizing epitope of the major outer membrane protein of
      Chlamydia trachomatis by anti-idiotypic antibodies.
AB  - The major outer membrane protein (MOMP) is a primary target antigen for the
      development of chlamydial vaccine. This protein is composed of four variable
      domains (I to IV) flanked by constant regions. Some of the variable domains
      contain antigenic determinants that elicit a neutralizing antibody response.
      Murine monoclonal antibodies (MAbs) against three nonoverlapping epitopes of MOMP
      were developed. One of these, called DP10, bound to all serovars, as shown by
      immunoblot analysis, and neutralized chlamydial infectivity for hamster kidney
      (HaK) cells in a complement-independent in vitro assay. Furthermore, analysis of
      the fine specificity of this MAb showed that it recognized a synthetic peptide
      contained within variable domain IV of the MOMP. Anti-idiotypic antibodies (aId)
      directed against this anti-MOMP MAb were produced in rabbits. These aId
      specifically bound to the relevant idiotype (DP10) and inhibited the binding of
      anti-MOMP MAb (DP10) to MOMP preparations in a dose-dependent fashion. The
      specificity of our aId for the binding site of anti-MOMP MAb is further suggested
      by the binding inhibition of affinity-purified aId to DP10 by the synthetic
      peptide defined by the idiotype. In addition, these aId also reacted with anti
      MOMP antisera from rats and mice, suggesting an idiotypic cross-reactivity
      between these species. Finally, immunization of naive mice with aId induced an
      antibody response directed against the peptide defined by our anti-MOMP MAb and
      with neutralizing activity. Taken together, these data suggest that aId mimic a
      neutralization site on MOMP and could serve as a surrogate antigen to induce
      protective immunity against Chlamydia trachomatis.

PMID- 7507889
TI  - Mapping of TH1 helper T-cell epitopes on major secreted mycobacterial antigen 85A
      in mice infected with live Mycobacterium bovis BCG.
AB  - TH1 cytokine secretion was examined in response to synthetic peptides of the 85A
      component of the major secreted, fibronectin-binding antigen 85 complex from
      Mycobacterium tuberculosis in seven different mouse strains infected with live M.
      bovis BCG. Twenty-eight overlapping 20-mer peptides covering the complete mature
      295-amino-acid (AA) protein were synthesized. Significant interleukin-2 (IL-2)
      and gamma interferon (IFN-gamma) secretion could be measured following in vitro
      stimulation of spleen cells with these peptides. H-2d haplotype mice reacted
      preferentially against the amino-terminal half of the protein, i.e., against
      peptide 5 (AA 41 to 60) and especially against peptide 11 (AA 101 to 120), which
      contained an I-Ed binding motif. H-2b haplotype mice, on the other hand, reacted
      against peptides from both amino- and carboxy-terminal halves of the protein,
      peptide 25 (AA 241 to 260) being the most potent stimulator of IL-2 and IFN-gamma
      production. (BALB/c x C57BL/6)F1 animals with the H-2d/b haplotype weakly
      recognized peptides specific for both parental lines. Finally, CBA/J (H-2k) and
      major histocompatibility complex class II mutant B6.C.bm12 mice, carrying a
      mutant I-A beta bm12 allele on an H-2b background, reacted only very weakly to
      the 85A peptides. Reactive T cells isolated from lungs of BCG-infected H-2b
      haplotype mice recognized the same epitopes as spleen cells, especially peptide
      25. These data confirm previous findings regarding the powerful IL-2 and IFN
      gamma-inducing properties of antigen 85 during infection with live M. bovis BCG.

PMID- 7507890
TI  - Differentiation of Pseudomonas aeruginosa pili based on sequence and B-cell
      epitope analyses.
AB  - The nucleotide sequences of three previously undescribed Pseudomonas aeruginosa
      pilin structural genes are presented. Comparisons of deduced pilin primary
      structure and flanking DNA sequence allowed placement of these and six previously
      published sequences into one of two groups. Epitope mapping, using overlapping
      immobilized peptides representing the pilin primary structure, with antipilin
      monoclonal antibodies revealed several B-cell determinants grouped near the
      carboxyl terminus of P. aeruginosa 1244 pilin. One determinant was found to
      reside near the pilin constant region. These determinants were found associated
      with the pili of 31 of 95 P. aeruginosa clinical isolates.

PMID- 7507891
TI  - Septicemia-inducing Escherichia coli O115:K"V165"F165(1) resists killing by
      porcine polymorphonuclear leukocytes in vitro: role of F165(1) fimbriae and
      K"V165" O-antigen capsule.
AB  - Escherichia coli O115:K"V165":F165(1) wild-type strain 5131 survives in the
      bloodstream of experimentally inoculated gnotobiotic pigs and induces septicemia,
      whereas its afimbriate (F165(1)-negative) TnphoA mutant M48 and its acapsular
      (K"V165"-negative) spontaneous mutant 5131a are both nonpathogenic. We evaluated
      the role of the mannose-resistant F165(1) fimbrial system and of the O-antigen
      K"V165" capsule in resistance to phagocytosis by porcine polymorphonuclear
      leucocytes (PMNLs) in vitro. F165(1)-positive strains (5131 and 5131a) attached
      to and were ingested by PMNLs at a significantly higher level than afimbrial
      mutant M48 (P < 0.001) after 1 h of incubation. During incubation of these
      strains with PMNLs for up to 6 h, parental strain 5131 resisted killing whereas
      afimbriate mutant M48 and acapsular mutant 5131a were gradually killed and were
      found at significantly lower numbers than the parental strain 5131 at 2 (P <
      0.05) and 6 (P < 0.001) h. When bacteria were opsonized with normal pig serum,
      the afimbriate and acapsular mutants survived less well than when the bacteria
      were nonopsonized. Upon examination by electron microscopy of PMNLs after 2 h of
      incubation with bacteria, structurally normal bacteria were observed more often
      within phagosomes of PMNLs incubated with the parental strain than within
      phagosomes of PMNLs incubated with the afimbriate or the acapsular mutant. The
      extracellular oxidative response (as tested by release of hydrogen peroxide) of
      PMNLs stimulated by phorbol myristate acetate was completely inhibited by F165(1)
      positive strains but only partially inhibited by the afimbriate mutant. These
      results suggest that the F165(1) fimbrial system may mediate adherence of E. coli
      O115 to PMNLs. Survival of the parental strain in the presence of PMNLs, which
      may be intracellular, is at least partially due to the presence of the F165(1)
      fimbrial system and of the O-antigen capsule K"V165". Furthermore, the presence
      of the F165(1) fimbrial system may contribute to the bacterial inhibition of the
      oxidative response of porcine PMNLs.

PMID- 7507894
TI  - Induction of Mycobacterium avium gene expression following phagocytosis by human
      macrophages.
AB  - Little is known about the bacterial factors that enable pathogenic mycobacteria
      to survive and multiply within the macrophages of the infected host. By preparing
      cDNA from Mycobacterium avium bacilli grown in human-derived macrophages and in
      broth culture and using subtractive hybridization to remove commonly expressed
      genes, a procedure was developed to identify genes of M. avium that are
      specifically expressed when the bacilli are growing within macrophages. Total RNA
      was isolated from M. avium recovered 5 days after infection of human macrophages
      and from bacilli grown in vitro in broth. Mycobacterial mRNAs were converted to
      cDNA by reverse transcription. Biotin-modified cDNAs prepared from M. avium grown
      in broth culture were used to subtract the housekeeping genes from the cDNAs of
      the macrophage-derived M. avium. After each round of subtraction, a sample of the
      unsubtracted cDNA was amplified, labeled, and hybridized to cosmid clones of M.
      avium DNA. After three rounds of subtraction, the amplified DNA hybridized to
      approximately 1% of the cosmid clones under stringent conditions. Although the
      majority of the genes that are induced in phagocytized M. avium cells are
      expressed in the broth-grown bacilli, one DNA fragment that was identified coded
      for an mRNA that is highly specific for M. avium in phagosomes. This procedure
      will be especially useful for identifying genes that are expressed in response to
      growth in specific environments from organisms with genetic systems that are not
      well characterized.

PMID- 7507892
TI  - Local immune response and protection in the guinea pig keratoconjunctivitis model
      following immunization with Shigella vaccines.
AB  - This study used the guinea pig keratoconjunctivitis model to examine the
      importance of route of administration (mucosal versus parenteral), frequency and
      timing of immunization (primary versus boosting immunization), and form of
      antigen given (live attenuated vaccine strain versus O-antigen-protein conjugate)
      on the production of protective immunity against Shigella infection. Since local
      immune response to the lipopolysaccharide (LPS) O-antigen of Shigella spp. is
      thought to be important for protection against disease, O-antigen-specific
      antibody-secreting cells (ASC) in the spleen and regional lymph nodes of
      immunized animals were measured by using an ELISPOT assay. Results indicated that
      protective efficacy was associated with a strong O-antigen-specific ASC response,
      particularly in the superficial ventral cervical lymph nodes draining the
      conjunctivae. In naive animals, a strong ASC response in the cervical lymph nodes
      and protection against challenge were detected only in animals that received a
      mucosal immunization. Protection in these animals was increased by a boosting
      mucosal immunization. While parenteral immunization alone with an O-antigen
      protein conjugate vaccine did not protect naive animals against challenge, a
      combined parenteral-mucosal regimen elicited enhanced protection without the
      addition of a boosting immunization. Although O-antigen-specific serum
      immunoglobulin A titers were significantly higher in animals receiving a mucosal
      immunization, there was no apparent correlation between levels of serum antibody
      and protection against disease.

PMID- 7507893
TI  - Neutralizing antibodies and immunoprotection against pertussis and tetanus
      obtained by use of a recombinant pertussis toxin-tetanus toxin fusion protein.
AB  - The currently available diphtheria-tetanus-whole-cell pertussis (DTP) vaccines
      are associated with a variety of problems, including undesirable side effects and
      inconsistent efficacy. These problems are probably related to the poor definition
      of such vaccines, especially with respect to the whole-cell component against
      pertussis. Ideal vaccines should include only immunoprotective antigens with no
      toxin activity. As an initial step towards obtaining a well-defined and
      simplified DTP vaccine, a pertussis toxin-tetanus toxin chimeric protein was
      constructed. A soluble form of the pertussis toxin S1 subunit was fused to the
      protective fragment C of tetanus toxin, and the recombinant hybrid protein was
      produced in Escherichia coli. The 75-kDa fusion protein (p75) was overexpressed
      as a soluble molecule and purified to near homogeneity by two consecutive
      chromatographic steps. Purified p75 retained its ability to bind to ganglioside
      GT1b, the receptor for tetanus toxin, and to be recognized by protective and
      neutralizing anti-pertussis toxin antibodies specific for conformational
      epitopes. When administered to mice, the hybrid protein was found to be nontoxic
      but immunogenic. In addition, it was capable of inducing strong protection
      against tetanus and some protection against pertussis, as well as eliciting a
      pertussis toxin-neutralizing antibody response. Although the levels of anti
      pertussis toxin antibodies were rather low, neutralizing titers of the immunized
      mice correlated well with anti-pertussis toxin titers, indicating that protective
      epitopes are conserved in the recombinant protein.

PMID- 7507895
TI  - Modulation of cell surface-associated mannoprotein antigen expression in
      experimental candidal vaginitis.
AB  - The monoclonal antibody (MAb) AF1 recognizes an oligosaccharide epitope present
      on highly immunogenic and immunomodulatory mannoproteins (MP) of Candida
      albicans. The expression of this epitope (AF1-MP) during experimental candidal
      vaginitis was studied in two strains of C. albicans (3153 and CA-2) which were
      equally vaginopathic but differed in the mode of hypha formation in the vagina.
      In both strains, immunofluorescence of vaginal samples, taken 1 h after
      challenge, revealed an intense, MAb AF1-specific labelling of the yeast cells.
      This labelling was very scarce in fungal cells taken at 24 h and on subsequent
      days during the development of filamentous forms. Electron-microscopic gold
      immunolabelling observations showed that molecules carrying AF1-MP spanned the
      entire cell wall in the initial yeast cells but were absent on the cell surface
      and in the outermost, capsular layer of the cell wall of the germ tubes and
      filamentous forms. In both strains, at any time and for any form of intravaginal
      growth, AF1-MP was clearly expressed in the cytoplasm and cytoplasmic vesicles,
      and was fully incorporated into the inner layers of the cell wall. As seen by
      immunofluorescence, the vaginal fluid from C. albicans-infected rats did not
      hinder the expression of AF1-MP on the yeast cells surface in vitro. In electron
      microscopic gold immunolabelling, a hypha-specific MAb (3D9) labelled the surface
      of the hyphal but not of the yeast cells of C. albicans harvested from rat
      vagina. Overall, these data strongly suggest that cell surface expression of MP
      antigen is modulated during intravaginal growth and morphogenesis of C. albicans.

PMID- 7507896
TI  - Analysis of toxinogenic functions associated with the RTX repeat region and
      monoclonal antibody D12 epitope of Escherichia coli hemolysin.
AB  - Amino acids (aa) 550 through 850 of the Escherichia coli hemolysin (HlyA) contain
      sequences important for several steps in cytolysis. These include the Ca(2+)
      binding glycine-rich tandem repeats recognized by the monoclonal antibody A10,
      the putative HlyC-dependent acylation site that corresponds to the monoclonal
      antibody D12 epitope, and the erythrocyte specificity domain which confers
      erythrolytic activity to the Pasteurella haemolytica leukotoxin. To further
      investigate the toxinogenic functions associated with this region of HlyA, we
      constructed mutants in the hlyA sequences coding for the repeat region and the
      D12 epitope. Mutants were analyzed for anti-HlyA antibody reactivity, cytolytic
      activities, target cell binding, Ca2+ requirements, and virulence. The D12
      epitope was mapped to aa 673 through 726, with portions of the epitope both amino
      terminal and carboxy terminal to aa 700. This region was necessary, but not
      sufficient, for toxin binding to erythrocytes. A substitution at aa 684 resulted
      in loss of the D12 epitope, while cytolytic activity was retained. The nature of
      the D12 epitope and its associated functions are discussed. The A10 epitope
      mapped to residues 745 through 829, corresponding to repeats 4 through 11.
      Insertions within the glycine-rich repeats resulted in mutant forms of HlyA which
      retained A10 reactivity but required increased Ca2+ for lytic activity. These in
      vitro effects on cytolysis corresponded to a significant decrease in HlyA
      mediated virulence in mice. HlyA from one insertion mutant was able to associate
      with leukocyte membranes under conditions that were Ca2+ deficient for cytolysis.
      The role of the glycine-rich repeats and Ca2+ in HlyA activity are discussed.

PMID- 7507897
TI  - Excision of large DNA regions termed pathogenicity islands from tRNA-specific
      loci in the chromosome of an Escherichia coli wild-type pathogen.
AB  - Uropathogenic Escherichia coli 536 (O6:K15:H31) carries two unstable DNA regions,
      which were shown to be responsible for virulence. These regions, on which the
      genes for hemolysin production (hly) and P-related fimbriae (prf) are located,
      are termed pathogenicity islands (PAI) I and II, and were mapped to positions 82
      and 97, respectively, on the E. coli K-12 linkage map. Sequence analysis of the
      PAI region junction sites revealed sequences of the leuX and selC loci specific
      for leucine and selenocysteine tRNAs. The tRNA loci function as the targets for
      excision events. Northern (RNA) blot analysis revealed that the sites of excision
      are transcriptionally active in the wild-type strain and that no tRNA-specific
      transcripts were found in the deletion mutant. The analysis of deletion mutants
      revealed that the excision of these regions is specific and involves direct
      repeats of 16 and 18 nucleotides, respectively, on both sides of the deletions.
      By using DNA long-range mapping techniques, the size of PAI I, located at
      position 82, was calculated to be 70 kb, while PAI II, mapped at position 97,
      comprises 190 kb. The excision events described here reflect the dynamics of the
      E. coli chromosome.

PMID- 7507898
TI  - Structures of cell wall mannans of pathogenic Candida tropicalis IFO 0199 and IFO
      1647 yeast strains.
AB  - We conducted a structural analysis of the cell wall mannans isolated from two
      Candida tropicalis strains, IFO 0199 and IFO 1647, exhibiting strong
      agglutinabilities against anti-Candida factor sera 5 and 6. The products released
      from these mannans by acid treatment were identified as the oligosaccharides,
      from biose to pentaose, consisting solely of beta-1,2-linked mannopyranose units
      corresponding to common epitopes of Candida albicans serotypes A and B (factor
      5). Mild acetolysis of acid- and alkali-treated mannans produced large amounts of
      hexaose and heptaose, Man rho beta 1-2Man rho beta 1-2Man rho alpha 1-2Man rho
      alpha 1-2Man rho alpha 1-2Man and Man rho beta 1-2Man rho beta 1-2Man rho beta 1
      2Man rho alpha 1-2 Man rho alpha 1-2Man, corresponding to the C. albicans
      serotype A-specific epitopes (factor 6). However, the homologous pentaose, Man
      rho beta 1-2Man rho alpha 1-2 Man, was not generated by this procedure. The
      oligosaccharides (biose to hexaose) obtained from the mannans by conventional
      acetolysis were composed exclusively of alpha-1,2-linked mannopyranose units.
      Therefore, the mannans of C. tropicalis IFO 0199 and IFO 1647 do not have the
      alpha-1,3-linked mannopyranose units previously observed in the mannans of C.
      albicans and Candida stellatoidea. The results of this study and previous
      findings indicate that the similarity of the antigenicities of three Candida
      species, C. albicans serotype A, C. stellatoidea type II, and C. tropicalis,
      reside in the beta-1,2 and alpha-1,2 linkages containing oligomannosyl side chain
      (factor 6) in the cell wall mannan.

PMID- 7507899
TI  - Novel proteins of Plasmodium falciparum identified by differential
      immunoscreening using immune and patient sera.
AB  - A differential serological screen of a lambda gt11 cDNA expression library of
      Plasmodium falciparum was performed in an attempt to identify novel and putative
      host-protective antigens of the parasite. The screening was done with two
      categories of sera: (i) acute-phase sera obtained from smear-positive acutely
      infected P. falciparum patients from various regions in India and (ii) immune
      sera taken from healthy, permanent adult residents of P. falciparum-endemic rural
      districts of Orissa in eastern India. These adults had not suffered from any
      clinical malarial symptoms for at least the previous 3 years at the time of serum
      collection. Sixty-five clones obtained by screening the lambda gt11 library with
      two immune serum samples were analyzed extensively with a total of 70 acutely
      infected patient serum samples. Eight of these clones failed to react with any of
      the patient sera. Each of these eight clones, when tested individually with 92
      serum samples from the immune group, reacted with a minimum of 43% of the samples
      from this category of sera. Thus, these eight epitopes may encode host-protective
      elements since they are not recognized by antibodies in the patient sera but
      react exclusively and extensively with the clinically immune set. Sequence
      analysis of two of these clones reveals that they are novel Plasmodium genes.

PMID- 7507901
TI  - Lack of effect of Candida albicans mannan on development of protective immune
      responses in experimental murine candidiasis.
AB  - Candida albicans mannoprotein (MAN) administered to mice before or during
      immunization with viable C. albicans downregulates MAN-specific delayed
      hypersensitivity. In the experiments reported here we determined the effect of
      MAN downregulation on protective immunity in minimally immunized mice, i.e., mice
      exposed to C. albicans either intradermally or intragastrically, and in maximally
      immunized mice, i.e., mice immunized by a combination of intradermal and
      intragastric exposure, in experimental systemic candidiasis. MAN suppression did
      not induce statistically significant alterations in the protective responses in
      experimental candidiasis, although 8 of 12 groups of mice treated with MAN had
      fewer CFU of C. albicans in their kidneys than their non-MAN-treated
      counterparts. The results emphasize the lack of correlation of delayed
      hypersensitivity with protection in candidiasis and suggest that MAN may contain
      epitopes involved in the protective response.

PMID- 7507900
TI  - Haemophilus influenzae resides and multiplies intracellularly in human adenoid
      tissue as demonstrated by in situ hybridization and bacterial viability assay.
AB  - The DNA oligomer 5'-d(TGCGGCCTCTCAGTCCCGCACTTTCATCTTCC)-3' specifically
      recognizes Haemophilus influenzae 16S rRNA. We report here the use of this
      oligonucleotide, with a fluorescein label tagged on its 5' end, as a probe for
      the in situ detection of nonencapsulated nontypeable H. influenzae in sections of
      adenoid tissue from 10 children who were clinically infection free but were
      having their adenoids removed because of nasal obstruction. In some cases, the
      reticular crypt epithelium was focally infiltrated by H. influenzae. The
      reservoir for these bacterial colonizations, in all likelihood long standing,
      seemed to be macrophage-like cells found in the subepithelial layers in all 10
      cases. These mononuclear cells contained up to 200 intracellular H. influenzae
      cells. In the transmission electron macroscope, macrophage-like cells with
      intracellular bacteria with coccoid morphology, at least some of which were
      dividing, were seen. Adenoid cell suspensions, enriched for macrophages by use of
      paramagnetic beads coated with monoclonal antibodies against the CD14 marker,
      yielded up to 1,100 CFU of nontypeable H. influenzae per 10(5) cells after
      killing of extracellular bacteria with gentamicin followed by mechanical lysis of
      the cells.

PMID- 7507902
TI  - Expression of a channel-like pathway for adenosine transport in Leishmania
      donovani promastigotes.
AB  - L. donovani promastigotes (MHOM/ET/67/HA3) transport adenosine by a route that is
      sensitive to inhibition by a nonspecific channel blocker, propranolol. At the
      logarithmic and stationary phases of growth, the transport of 1 microM-3H
      adenosine was significantly inhibited (40-50%) by 100 microM-propranolol. In
      contrast, a strain of Leishmania donovani promastigotes clonally selected to grow
      in defined medium was only slightly (approximately 10%) inhibited at the
      logarithmic but not at the stationary phase. These results suggest that the
      differences in expression of adenosine in the parasites previously reported, may
      be related to uptake by a channel-like pathway in the promastigotes.

PMID- 7507904
TI  - Oxygen-induced retinopathy in the mouse.
AB  - PURPOSE: To develop oxygen-induced retinopathy in the mouse with reproducible and
      quantifiable proliferative retinal neovascularization suitable for examining
      pathogenesis and therapeutic intervention for retinal neovascularization in
      retinopathy of prematurity (ROP) and other vasculopathologies. METHODS: One-week
      old C57BL/6J mice were exposed to 75% oxygen for 5 days and then to room air. A
      novel fluorescein-dextran perfusion method has been developed to assess the
      vascular pattern. The proliferative neovascular response was quantified by
      counting the nuclei of new vessels extending from the retina into the vitreous in
      6 microns sagittal cross-sections. Cross-sections were also stained for glial
      fibrillary acidic protein (GFAP). RESULTS: Fluorescein-dextran angiography
      delineated the entire vascular pattern, including neovascular tufts in flat
      mounted retinas. Hyperoxia-induced neovascularization occurred at the junction
      between the vascularized and avascular retina in the mid-periphery. Retinal
      neovascularization occurred in all the pups between postnatal day 17 and
      postnatal day 21. There was a mean of 89 neovascular nuclei per cross-section of
      9 eyes in hyperoxia compared to less than 1 nucleus per cross-section of 8 eyes
      in the normoxia control (P < 0.0001). Proliferative vessels were not associated
      with GFAP-positive astrocyte processes. CONCLUSIONS: The authors have described a
      reproducible and quantifiable mouse model of oxygen-induced retinal
      neovascularization that should prove useful for the study of pathogenesis of
      retinal neovascularization as well as for the study of medical intervention for
      ROP and other retinal angiopathies.

PMID- 7507905
TI  - Effect of light on oxygen-induced retinopathy in the mouse.
AB  - PURPOSE: To examine the effect lf light on retinal neovascularization and
      vasculogenesis in a reproducible and quantifiable model of oxygen-induced
      proliferative retinopathy in the mouse. METHODS: C57Bl/6J mice were reared in
      room air, 68% oxygen, or 75% oxygen and were exposed to darkness, low cyclical
      light (200-350 lux), or high-intensity continuous light (3000-4500 lux). The
      entire retinal vascular pattern was visualized in fluorescein-dextran perfused
      flat-mount preparations. Proliferative retinopathy was quantified by counting
      neovascular nuclei in 6 microns cross-sections of whole eyes. RESULTS: Light
      exposure did not exacerbate the proliferative retinopathy that was seen after 68%
      oxygen exposure, which induced a meager proliferative response, nor after 75%
      oxygen exposure, which induced an exuberant proliferative response. In room air,
      retinas from all three illumination groups had normal vascular patterns.
      CONCLUSIONS: In this model of oxygen-induced retinopathy, under the conditions
      tested, light neither exacerbated the hyperoxia-induced neovascularization nor
      affected normal retinal vascular development.

PMID- 7507903
TI  - The effect of diamphenethide on protein synthesis by the liver fluke, Fasciola
      hepatica.
AB  - The effect of the deacetylated (amine) metabolite of diamphenethide (DAMD, 10
      micrograms ml-1) on the uptake and incorporation by adult Fasciola hepatica of
      radioactively labelled precursors of DNA, RNA and protein synthesis
      ([3H]thymidine, [3H]uridine and [3H]leucine, respectively) was measured by liquid
      scintillation counting. Comparison was made between the effects of DAMD and those
      of specific inhibitors of DNA, RNA and protein synthesis, namely, 5-fluorouracil,
      cordycepin and cycloheximide, respectively. DAMD caused a significant decrease in
      the overall uptake and incorporation of [3H]uridine by F. hepatica, decreased the
      incorporation of [3H]leucine and also caused a significant decrease in the
      overall protein content of the flukes. The effect of DAMD was similar to that of
      cycloheximide (1 x 10(-3) M), a potent inhibitor of protein synthesis, which also
      caused a significant decrease in the incorporation of [3H]leucine by the fluke
      and a decrease in the overall protein content of the fluke. Cordycepin (100
      micrograms ml-1) caused a significant decrease in the protein content of the
      fluke, but had no effect on the uptake or incorporation of [3H]uridine. 5
      Fluorouracil (1 x 10(-4) M) did not affect the uptake or incorporation of
      [3H]thymidine, nor did it decrease the protein content of the fluke. The results
      indicate that DAMD inhibits protein synthesis by F. hepatica, possibly by
      inhibiting RNA synthesis. The results are also consistent with previous
      morphological investigations involving DAMD.

PMID- 7507906
TI  - Identification of origin of two polypeptides of 4 and 5 kD isolated from human
      lenses.
AB  - PURPOSE: To purify crystallin fragments (degraded polypeptides molecular weight <
      18 kD) and identify their parent crystallins. METHODS: The purification of
      polypeptides with apparent molecular weights of 4 and 5 kD was carried out using
      three sequential steps: Sephadex G-50 chromatography under denaturing conditions,
      preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and high
      performance liquid chromatography using a C-18 column. The parent crystallins of
      the two polypeptides were identified by the Western blotting method using
      polyclonal antibodies raised against individual 4 and 5 kD polypeptides and by
      comparing N-terminal amino acid sequences of the polypeptides with crystallins.
      RESULTS: Two polypeptides of 4 and 5 kD were purified by the three sequential
      steps as described from water-soluble proteins of lenses from 60-80-year-old
      donors. Both purified polypeptides showed a single major peak during high
      performance liquid chromatography on a C-18 column and also a single band during
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The Western blot
      analyses showed maximum immunoreactivity of the anti-4 kD polypeptide antibody to
      a 22 kD species of beta-crystallin, whereas the anti-5 kD polypeptide antibody
      showed maximum reactivity to only the alpha B crystallin. These results were
      further confirmed during comparison of the N-terminal amino acid sequences of the
      two polypeptides with crystallins. Such comparison showed that the 4 kD
      polypeptide originated from beta A 3/A1 crystallin after cleavage at His187
      His188 bond. Further, the 5 kD polypeptide was a fragment of alpha B crystallin
      that originated after cleavage at Val145-Asn146 bond. CONCLUSION: These results
      showed that specific bonds of beta A3/A1 and alpha B crystallins are
      posttranslationally cleaved in vivo to produce 4 kD and 5 kD polypeptides,
      respectively.

PMID- 7507907
TI  - Phototransduction mechanism in retinal rods and cones. The Friedenwald Lecture.

PMID- 7507908
TI  - Dentine proteoglycans: composition, ultrastructure and functions.
AB  - Proteoglycans (PGs) have been visualized in the predentine and dentine with
      cationic dyes by staining thin sections with Alcian Blue, bismuth nitrate, or
      using Spicer's high-iron diamine (HID) method. The precise location may be
      obtained by adding cationic dyes such as Cuprolinic Blue, ruthenium hexamine
      trichloride or cationic detergent (cetylpyridinium chloride) to the fixative.
      These methods induced the formation of aggregates which varied in shape and
      number according to the method used. Rapid freezing followed by freeze
      substitution revealed an amorphous ground substance, homogeneously stained with
      Alcian Blue, located in the predentine between the collagen fibres. These PGs may
      be involved in transport and diffusion in predentine. In dentine, small granules
      and needle-like structures were observed along the collagen fibres. This second
      group of PGs differs in composition, distribution and functions from the
      predentine PGs. The same distribution was seen when hyaluronidase-gold labelling
      was used. Labelling with antibodies and autoradiography also gave evidence of two
      distinct groups of PGs. In predentine, as an hydrated gel, PGs seems to act as
      mineral inhibitors, whereas immobilized on a surface, as seen at the dentine
      edge, they act as nucleating agents. The interaction between PGs and
      phospholipids seems also to play a role in the mineralization process.

PMID- 7507909
TI  - Mechanism of connective tissue techniques. I. The effect of dye concentration and
      staining time on anionic dye procedures.
AB  - Anionic dye connective tissue procedures were performed by staining for 5 min and
      24 h with (a) 0.00018 M and 0.0018 M solutions of 28 dyes, and 0.018 M solutions
      of 21 dyes in saturated picric acid (SPA), and (b) 0.0018 M and 0.018 M solutions
      of 20 dyes in 1% (w/v) phosphomolybdic acid (PMA). The staining obtained with
      dyes in SPA was classified as selective (no cytoplasmic staining), moderately
      selective (traces of cytoplasmic staining) and non-selective (all other staining
      patterns). The staining of collagen and cytoplasm with dyes in PMA was separately
      classified on a scale of 1-5 (1 = no staining, 5 = maximum staining). The
      selectivity of the staining obtained with SPA with solutions of dyes at
      concentrations of 0.00018 M and 0.0018 M, and both staining times, was correlated
      (p < 0.001) with an empirical sulphonic acid constant (SAC) defined as the
      (number of dye sulphonic acid groups/dye molecular weight) x 10(3). Correlation
      with molecular weight was poor and was significant only when staining was
      performed with 0.00018 M dye solutions for 24 h. The dyes were divisible into
      three groups: group 1 (selectivity independent, or almost independent of staining
      time), group 2 (selective to moderately selective when staining was performed for
      5 min), and group 3 (non-selective). The SAC of the group 1 dyes differed
      significantly from those of the group 2 and 3 dyes. Selectivity was essentially
      lost at dye concentrations of 0.018 M. The staining with acidic dyes (no amines
      or substituted amines) in PMA differed significantly (p < 0.001) from that
      obtained with amphoteric dyes (containing basic substituents).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7507910
TI  - Immunofluorescent localization of platelet-activating factor (PAF) in the rat.
AB  - An immunofluorescent staining method for detecting platelet-activating factor
      (PAF) is described. This method employs a polyclonal anti-PAF rabbit antibody.
      When rat brain, heart, lung, liver or kidney tissue was stained using this
      method, the heart, lung and kidney exhibited PAF-specific staining. Analysis of
      the amount of PAF in different organs, either by immunofluorescence or by
      bioassay, showed that kidney tissue contains the greatest amount of PAF.

PMID- 7507913
TI  - Histochemical evidence for microglia-like macrophages in the rat trigeminal
      ganglion.
AB  - Of the 4 major cell types in CNS parenchyma, microglia appear to serve the unique
      functional role of tissue macrophages. The distribution of equivalent cells in
      the PNS is unclear. Recently, the B4 isolectin of Griffonia simplicifolia was
      shown to bind selectively to microglia as well as to other macrophages under
      specific conditions. In the present study, this lectin was used to assess the
      existence of macrophages in the rat trigeminal ganglion. Vibratome sections of
      fixed ganglia were incubated with horseradish peroxidase (HRP)-conjugated
      isolectin, an HRP reaction subsequently performed, and sections processed for
      histology and viewed by light microscopy. Staining activity was found to be
      localised to a population of cells throughout the ganglion. These cells possessed
      small oval somata and several thin crenated processes, an appearance typical of
      ramified microglia. Stained cells also exhibited a regular, evenly spaced tissue
      distribution similar to CNS microglia. Finally, similar cells were also labelled
      by thiamine pyrophosphatase histochemistry, a cellular marker for CNS
      microglia/macrophages. It was concluded that there are microglia-like macrophages
      in the trigeminal ganglion and that these cells may function in immune reactions.

PMID- 7507914
TI  - Confocal and conventional immunofluorescence and ultrastructural localisation of
      intracellular strength-giving components of human amniochorion.
AB  - Key cytoskeletal polypeptides of human fetal membranes have been localised at
      subcellular level using confocal and conventional indirect immunofluorescence
      microscopy. Correlation with electron microscope data has allowed us to examine
      how cellular compartments of this multilaminar tissue maintain their mechanical
      integrity until the time of membrane rupture at parturition. Evidence is
      presented for myofibroblastic characteristics of cells in both the fibroblast and
      reticular layers which may therefore have tension-generating, position-adjustment
      and wound-healing roles in the amniochorion. Desmin and vimentin are coexpressed
      in these cells, but a small localised population of cells in the fibroblast layer
      contains vimentin alone. An interaction of cytokeratin filaments with nuclei and
      desmosomes of amniotic epithelium in vivo is demonstrated, indicating that nuclei
      of cells of ectodermal origin are integrated into a mechanical structure
      extending throughout the tissue as a whole. Cells of the basal 1 or 2 layers of
      trophoblast have been shown to have a more extensive and better integrated
      cytoskeletal organisation than those overlying and forming the boundary with
      decidua. Structures within the trophoblast, identified previously as degenerate
      villi, contain cells with intermediate filaments with similar immunofluorescence
      properties to those of the neighbouring reticular layer and thus may represent
      papillae that prevent shearing at this interface.

PMID- 7507912
TI  - Monoclonal antibodies recognising stage and region specific epitopes in embryonic
      mouse palatal epithelial cells.
AB  - Four monoclonal antibodies raised against murine embryonic palatal epithelium
      were used to stain frontal cryosections of embryonic mouse heads (d 11-15). One
      antibody (6A11) recognised the nasal epithelium at the angle of the palate prior
      to shelf elevation (embryonic d 11-d 13) and the epithelia at the tips of the
      approximated shelves (embryonic d 14.5). Two further antibodies (2H6 and 3H2)
      recognised epitopes on the entire palatal epithelium until shelf elevation
      (embryonic d 14.5) when their expression ceased. The epitope recognised by
      antibody 6D3 was absent from the palatal epithelium until embryonic d 13 when it
      displayed region specific expression, being present on the nasal aspect in the
      midpalate and the tip of the palate posteriorly. On embryonic d 14.5 staining of
      the medial edge epithelia was present in all regions. Whilst the nasal palatal
      epithelium stained in the anterior and mid regions, only patchy staining of the
      oral epithelium was detected. By embryonic d 15 staining was present throughout
      the palatal epithelia. These antibodies are directed against intracellular
      epitopes, possibly keratins. Indeed, immunoblotting assays revealed that antibody
      2H6 recognised keratin 18. The developmental regulation of the epitopes
      recognised by the antibodies corresponds with differentiative events occurring
      during murine palatogenesis.

PMID- 7507915
TI  - Immunohistochemical and semiquantitative study of the apical mitochondria-rich
      cells of the human prepubertal and adult epididymis.
AB  - An immunohistochemical and semiquantitative study of the apical mitochondria-rich
      cells (AMRC) in the caput, corpus and cauda of the human epididymis from the
      fetal period to adulthood was performed on autopsy specimens from normal males
      without testicular or associated pathology. The immunohistochemical pattern of
      AMRC differed from that of the principal cells (PC). AMRC showed a more intense
      immunoreaction to several keratin types (AE1 and AE3 keratin complexes, and
      keratins 18 and 19) and to oestradiol-related protein receptors than did PC. In
      addition, immunostaining with antibodies to epithelial membrane antigen was
      intense in PC and weak in AMRC. Two immunohistochemical types of basal cells were
      observed: one was similar to the AMRC and the other to PC. PC and AMRC were
      already present in fetuses of 24-27 wk gestation. Basal cells were only
      occasionally observed at this age, but became much more numerous in the 28-33 wk
      fetuses. No changes in the immunohistochemical patterns of any of these cell
      types were found during infancy and adulthood. The numbers of PC per unit length
      of basement membrane were very similar in the 3 epididymal regions and at all
      ages studied. In all age groups, the number of AMRC decreased from caput to cauda
      epididymis. In the caput and corpus, the number of AMRC rose during the fetal
      period and the first 6 months after birth and thereafter decreased progressively
      during infancy and adulthood.

PMID- 7507911
TI  - Noncholinergic control of adrenal catecholamine secretion.
AB  - It has been known for over 70 years that adrenal catecholamine secretion can be
      modulated or elicited by noncholinergic neurotransmitters and hormones. However,
      our understanding of the cellular mechanisms by which these agents produce their
      effects and the physiological conditions under which they act are not well
      characterised. Here we briefly review the mechanisms by which one such agent (the
      neuropeptide substance P) modulates the cholinergic secretory response of adrenal
      chromaffin cells, and another agent (angiotensin II) elicits catecholamine
      secretion independently of the cholinergic innervation.

PMID- 7507917
TI  - Oral and poster presentations.

PMID- 7507916
TI  - Interferon in chronic hepatitis B.

PMID- 7507918
TI  - Initiator transfer RNAs.

PMID- 7507919
TI  - Regulation of alpha- and beta-hemolysins by the sar locus of Staphylococcus
      aureus.
AB  - We recently identified a locus on the Staphylococcus aureus chromosome,
      designated sar, for staphylococcal accessory regulator, that is involved in the
      global regulation of extracellular and cell wall-associated proteins. Previous
      phenotypic and Southern blot analyses with Tn917 and agr probes indicated that
      this locus is distinct from agr, a previously described global regulator of
      exoproteins in S. aureus. To understand the mode of regulatory control of
      exoprotein synthesis by the sar locus, the sar genotype was transduced from the
      original sar mutant 11D2 into two prototypic S. aureus strains, RN6390 and RN450,
      with well-defined genetic backgrounds. An analysis of extracellular protein
      profiles by use of silver-stained sodium dodecyl sulfate gels revealed
      alterations in the pattern of exoprotein production in the late log-early
      stationary phase in the sar mutants in comparison with the corresponding parents.
      In addition, most of the phenotypic changes that occurred in the conversion from
      the sar+ genotype to the sar genotype in mutant 11D2 were also found in these
      mutants. Northern (RNA) blot analyses of two exoprotein transcripts (alpha- and
      beta-hemolysins) from strain RN6390 and its corresponding sar mutant revealed
      downregulation of these transcripts in the mutant. Serial studies of these
      hemolysin transcripts at various growth intervals demonstrated that the
      transcriptional regulation of the hemolysin genes by the sar locus began during
      the log phase and continued into the postexponential phase. These data suggested
      that the sar locus probably regulates exoprotein genes at the transcriptional
      level. This mode of regulation is similar to that of exoprotein target gene
      transcription by agr.

PMID- 7507920
TI  - Characterization of the rfc region of Shigella flexneri.
AB  - The O antigen of the Shigella flexneri lipopolysaccharide (LPS) is an important
      virulence determinant and immunogen. We have isolated S. flexneri mutants which
      produce a semi-rough LPS by using an O-antigen-specific phage, Sf6c. Western
      immunoblotting was used to show that the LPS produced by the semi-rough mutants
      contained only one O-antigen repeat unit. Thus, the mutants are deficient in
      production of the O-antigen polymerase and were termed rfc mutants.
      Complementation experiments were used to locate the rfc adjacent to the rfb genes
      on plasmid clones previously isolated and containing this region (D. F.
      Macpherson, R. Morona, D. W. Beger, K.-C. Cheah, and P. A. Manning, Mol.
      Microbiol 5:1491-1499, 1991). A combination of deletions and subcloning analysis
      located the rfc gene as spanning a 2-kb region. Insertion of a kanamycin
      resistance cartridge into a SalI site in this region inactivated the rfc gene.
      The DNA sequence of the rfc region was determined. An open reading frame spanning
      the SalI site was identified and encodes a protein with a predicted molecular
      mass of 43.7 kDa. The predicted protein is highly hydrophobic and showed little
      sequence homology with any other protein. Comparison of its hydropathy plot with
      that of other Rfc proteins from Salmonella enterica (typhimurium) and Salmonella
      enterica (muenchen) revealed that the profiles were similar and that the proteins
      have 12 or more potential membrane-spanning segments. A comparison of the S.
      flexneri rfc gene and protein product with other rfc and rfc-like proteins
      revealed that they have a similarly low percentage of G + C content and have
      similar codon usage, and all have a high percentage of rare codons. An attempt to
      identify the S. flexneri Rfc protein was unsuccessful, although proteins encoded
      upstream and downstream of the rfc gene could be identified. Examination of the
      distribution of rare or minor codons in the rfc gene revealed that it has several
      minor codons within the first 25 amino acids. This is in contrast to the upstream
      gene rfbG, which also has a high percentage of rare codons but whose gene product
      could be detected. The positioning of the rare codons in the rfc gene may
      restrict translation and suggests that minor isoaccepting tRNA species may be
      involved in translational regulation of rfc expression. The low percentage of G +
      C content of rfc genes may be a consequence of the selection pressure to maintain
      this form of control.

PMID- 7507922
TI  - What's new in treatment?

PMID- 7507921
TI  - Genetic and molecular characterization of the Escherichia coli secD operon and
      its products.
AB  - The secD operon of Escherichia coli is required for the efficient export of
      proteins. We have characterized this operon, and found that, in addition to secD
      and secF, it contains the upstream gene yajC, but not the genes queA or tgt, in
      contrast to previous reports. An analysis of yajC mutations constructed in vitro
      and recombined onto the chromosome indicates that yajC is neither essential nor a
      sec gene. The secD operon is not induced in response to either secretion defects
      or temperature changes. TnphoA fusions have been used to analyze the topology of
      SecD in the inner membrane; the protein contains six transmembrane stretches and
      a large periplasmic domain. TnphoA fusions to SecD and SecF have also been
      recombined onto the chromosome and used to determine the level of these proteins
      within the cell. Our results indicate that there are fewer than 30 SecD and SecF
      molecules per cell.

PMID- 7507923
TI  - Tyrosine phosphorylation of protein kinase C-delta in response to its activation.
AB  - Retroviral vectors containing five different protein kinase C (PKC) isoenzymes
      (alpha, delta, epsilon, eta, zeta) were expressed in 32D hematopoietic cells and
      NIH-3T3 fibroblasts. In an effort to investigate signaling events regulated by
      PKC activation, we analyzed whether tyrosine phosphorylation of cellular proteins
      would occur after 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment of the
      various transfectants. While no detectable tyrosine-specific phosphorylation was
      observed after treatment of the majority of the transfectants, pronounced TPA
      dependent tyrosine phosphorylation of an 82-kDa protein was detected in the
      32D/PKC-delta and NIH-3T3/PKC-delta lines. Interestingly, the 82-kDa substrate
      proved to be PKC-delta itself. Tyrosine phosphorylation of purified PKC-delta by
      src family or receptor tyrosine kinases in vitro enhanced PKC-delta activity,
      suggesting that tyrosine phosphorylation of PKC-delta may positively affect its
      function.

PMID- 7507924
TI  - Production of single-stranded DNA in mammalian cells by means of a bacterial
      retron.
AB  - msDNA-Ec67, a peculiar multicopy single-stranded DNA of a specific sequence was
      produced in NIH3T3 mouse cells. Retron-Ec67, a retroelement from Escherichia
      coli, was introduced under the T7 polymerase promoter and the non-translated 5'
      region of the encephalomyocarditis virus. The construct was then transfected into
      the NIH3T3 cells constitutively producing T7 RNA polymerase. Forty-eight hours
      after transfection, msDNA-Ec67 was detected in the cells by means of Southern
      blot hybridization and reverse transcriptase extension assay. The potential use
      of bacterial retrons as a vector for single-stranded DNA production in mammalian
      cells is discussed.

PMID- 7507925
TI  - The role of pyruvate in neuronal calcium homeostasis. Effects on intracellular
      calcium pools.
AB  - It has long been known that pyruvate is essential for survival of prenatal
      neurons in culture. To understand the role of exogenous pyruvate in neuronal
      calcium homeostasis, we have investigated the effects of pyruvate (plus malate)
      addition to dissociated adult rat hippocampal and cerebral cortex cells and
      cultured CNS neurons having an unrestricted glucose supply. We found that
      pyruvate (plus malate) increased the respiration rate while ATP levels were
      unchanged. At the same time, cytosolic free calcium concentrations, [Ca2+]i,
      decreased while total 45Ca2+ and 40Ca2+ accumulation increased. The extra Ca2+
      accumulated by the cells is attributable to an increase in the size of the
      intracellular calcium pools. Two such pools were identified on the basis of their
      sensitivity to specific drugs. The first pool was mobilized by thapsigargin plus
      tert-butyl hydroquinone and caffeine while the second pool was discharged by the
      mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxphenylhydrazone (FCCP)
      (plus oligomycin). The two pools represented about 15-20% and 15-30%,
      respectively, of the rapidly exchangeable 45Ca2+ pools in cerebral cortex cells.
      In cultured hippocampal neurons, the collapse of the mitochondrial membrane
      potential (as induced by uncouplers (FCCP) or respiratory chain inhibitors
      (antimycin) caused a large increase in [Ca2+]i which varied in size and shape
      among cells and was reduced by external Ca2+ chelation. The latter condition also
      resulted in a partial discharge of FCCP-releasable 45Ca2+. The effects of FCCP
      did not result simply from ATP depletion since incubation in glucose-free medium
      and sequential additions of 2 mM deoxyglucose and 10 microM oligomycin,
      conditions that led to a dramatic reduction in cellular ATP levels, did not
      abolish the FCCP-induced [Ca2+]i rise. Taken together, the results indicate that
      mitochondria harbor a significant proportion of cellular Ca2+. The sensitivity of
      the mitochondrial pool size to pyruvate (plus malate) questions previous
      hypotheses concerning a kinetic limitation for Ca2+ accumulation in mitochondria
      in resting neurons.

PMID- 7507926
TI  - Structural analysis of mouse glycine receptor alpha subunit genes. Identification
      and chromosomal localization of a novel variant.
AB  - The inhibitory glycine receptor is a ligand-gated ion channel protein that occurs
      in different developmentally regulated isoforms in the mammalian central nervous
      system. Here, we have analyzed genomic clones covering the coding regions of the
      murine glycine receptor alpha 1 and alpha 2 subunit genes. Both genes contain
      eight intronic regions with precisely conserved boundaries. The same structure
      was also found for seven exons of a third homologous gene, alpha 4, identified
      during screening. The predicted alpha 4 polypeptide displays very high homology
      to the alpha 2 subunit. Like the alpha 2 gene, the alpha 4 gene maps to the mouse
      X chromosome. Our data indicate that the genomic organization of glycine receptor
      alpha subunit genes is conserved during evolution.

PMID- 7507927
TI  - The somatomedin B domain of vitronectin. Structural requirements for the binding
      and stabilization of active type 1 plasminogen activator inhibitor.
AB  - We recently localized the high affinity binding site for activated type 1
      plasminogen activator inhibitor (PAI-1) to the somatomedin B domain (i.e. amino
      acid (aa) 1-51) of vitronectin (Vn). In this study to further define this site, N
      terminal Vn fragments of various lengths were expressed in Escherichia coli and
      tested for PAI-1 binding activity. Vn polypeptides containing aa 1-52 and 1-40
      retained PAI-1 binding activity and stabilized PAI-1 to a similar extent as
      intact Vn, but polypeptides containing aa 1-30 did not bind to PAI-1 nor
      stabilize its activity. The effects of monoclonal antibodies (mAbs) to Vn on PAI
      1 binding was also determined. One mAb bound to Vn and blocked its ability to
      bind to PAI-1. It also dissociated pre-existing PAI-1.Vn complexes, and prevented
      the incorporation of PAI-1 into extracellular matrix of HT 1080 cells. This mAb
      bound to the recombinant peptide containing aa 1-40, but not to the peptide
      consisting of aa 1-30. A second randomly chosen mAb with similar affinity for Vn
      was inactive in these assays and bound to the region between aa 52 and 239. These
      results indicate that the high affinity binding site for active PAI-1 in Vn is
      between aa 1 and 40, and that this domain may also stabilize active PAI-1.

PMID- 7507928
TI  - A highly conserved tyrosine residue in G protein-coupled receptors is required
      for agonist-mediated beta 2-adrenergic receptor sequestration.
AB  - An aromatic residue, tyrosine 326 in the prototypical human beta 2-adrenergic
      receptor, exists in a highly conserved sequence motif in virtually all members of
      the G protein-coupled receptor family. The potential role of this conserved
      aromatic amino acid residue in the cellular processes of sequestration (a rapid
      internalization of the surface receptor) and down-regulation (a slower loss of
      total cellular receptors) associated with agonist-mediated desensitization of the
      beta 2-adrenergic receptor was assessed by replacing tyrosine residue 326 with an
      alanine residue (beta 2AR-Y326A). This mutation completely abolishes agonist
      mediated receptor sequestration without affecting the ability of the receptor to
      activate maximally adenylyl cyclase, to undergo rapid desensitization, and to
      down-regulate in response to agonist. The only other major change associated with
      the mutated receptor is a complete loss of the ability to resensitize following
      rapid desensitization. These results imply that this tyrosine residue, which is
      part of a highly conserved sequence motif in G protein-coupled receptors, may be
      responsible for their agonist-mediated sequestration and that sequestration and
      down-regulation of the receptor are dissociable phenomena. The lack of
      resensitization in the sequestration-defective beta 2-adrenergic receptor mutant
      strongly suggests that the sequestration pathway is an important mechanism by
      which cells re-establish the normal responsiveness of G protein-coupled receptors
      following the removal of agonist.

PMID- 7507929
TI  - Human endothelial cells are targets for platelet-activating factor (PAF).
      Activation of alpha and beta protein kinase C isozymes in endothelial cells
      stimulated by PAF.
AB  - We evaluated the role of the protein kinase C (PKC) and its isozymes in the
      activation of human endothelial cells (EC) stimulated by platelet-activating
      factor (PAF). Exposure of confluent EC to PAF resulted in a rapid and
      concentration-dependent redistribution of PKC from cytosol to plasma-membrane,
      rearrangement of cytoskeleton (i.e. decrease in F-actin content and
      redistribution of vinculin), and finally increase in the transendothelial flux of
      125I-albumin. Stimulation of EC with oleylacetylglycerol or phorbol 12-myristate
      13-acetate induced the modification of the cytoskeletal structures and the
      increase of 125I-albumin clearance. Inhibitors of PKC prevented the effects
      induced by PAF on the cytoskeleton and on the barrier function of the EC
      monolayer. Confluent EC expressed only alpha, beta, and epsilon PKC isoforms.
      Biochemical and immunochemical analysis showed that the time course of the PKC
      isozymes translocation from cytosol to the membrane fraction of EC stimulated by
      PAF was different: beta isoform was redistributed more quickly than alpha
      isoform. PAF did not induce translocation of PKC epsilon. These results suggest
      that activation of PKC alpha and beta is an important signal transduction pathway
      by which PAF activates endothelial monolayer and modify its function of barrier
      to macromolecules.

PMID- 7507930
TI  - Immunoelectron microscopy of epitopes on Na,K-ATPase catalytic subunit.
      Implications for the transmembrane organization of the C-terminal domain.
AB  - The transmembrane folding of the alpha subunit of Na,K-ATPase was studied by
      using immunoelectron microscopy to determine whether monoclonal antibodies with
      defined epitopes bind to the extracellular or cytoplasmic surface. In double
      labeling experiments, an antibody and a reference marker were bound to purified
      membrane-associated Na,K-ATPase and were visualized by employing colloidal gold
      particles of two different sizes. Wheat germ agglutinin and a previously
      characterized monoclonal antibody were used as control markers for the exoplasmic
      and cytoplasmic surfaces, respectively. Three antibodies, VG4, VG2, and IIC9,
      unambiguously bound to the extracellular surface. Previously IIC9 had been
      assigned to the cytoplasmic surface because, in immunofluorescence studies, it
      stained intact cells only when they were detergent-permeabilized. To investigate
      the basis for this contradiction, a third assay for sidedness was used:
      competition binding in solution to right-side-out renal medullary vesicles. IIC9
      was found to bind to the extracellular surface of sealed vesicles, but only in
      certain experimental conditions. It was concluded that IIC9 has an epitope that
      is not always accessible and that in this instance, studies of binding to intact
      and detergent-treated cells had given misleading results. An extracellular
      disposition for all three antibodies is not compatible with existing folding
      models, and new models are presented.

PMID- 7507931
TI  - Changes in the structure and function of the human thrombin receptor during
      receptor activation, internalization, and recycling.
AB  - According to current models, human thrombin receptors are activated when thrombin
      cleaves the receptor's N terminus, exposing the tethered ligand domain, SFLLRN.
      In the megakaryoblastic CHRF-288 cell line, thrombin receptor activation is
      followed by the rapid internalization of > 90% of the receptors. In the present
      studies, antibodies directed at the site of cleavage by thrombin were used to
      examine changes in receptor structure during activation, internalization, and
      recovery. As would be expected, the initial rate of receptor cleavage was
      directly related to the thrombin concentration. However, even after prolonged
      incubation, receptor cleavage was incomplete until the thrombin concentration
      exceeded the receptor concentration. Only cleaved receptors were internalized in
      response to thrombin and only catalytically active thrombin and active variants
      of SFLLRN-containing peptides caused receptor internalization. Over a 3-h period
      following receptor activation by thrombin, there was a gradual recovery of
      approximately one-quarter of the receptors on the cell surface. These receptors
      were detectable with antibodies directed at retained portions of the receptor N
      terminus, but not with antibodies directed at the proposed site of cleavage,
      confirming that they are recycled, rather than new, receptors. At 4 degrees C two
      thirds of the receptors cleaved by thrombin were retained on the cell surface.
      Like recycled receptors these "cold-cleaved" receptors failed to self-activate
      when warmed to 37 degrees C, but could be activated by SFLLRN. Unlike recycled
      receptors, however, the cold-cleaved receptors were also internalized and
      appeared to be activated by a second addition of thrombin. These results 1)
      provide strong evidence at the protein level that thrombin cleaves its receptors
      at the predicted site, 2) show that receptor activation is necessary for
      internalization, 3) suggest that each thrombin molecule may not activate large
      numbers of receptors, 4) demonstrate that a substantial fraction of internalized
      thrombin receptors can be recycled, and 5) suggest that the failure of recycled
      receptors to be reactivated by thrombin may involve a change in the receptor that
      does not occur at 4 degrees C. Finally, the inability of cold-cleaved receptors
      to self activate in the absence of thrombin, suggests that in addition to
      cleaving the receptor, thrombin may also play an important role in guiding the
      tethered ligand domain to regions on the remainder of the receptor that mediate
      activation.

PMID- 7507932
TI  - Stoichiometry of recombinant cystic fibrosis transmembrane conductance regulator
      in epithelial cells and its functional reconstitution into cells in vitro.
AB  - We have generated several clones of Chinese hamster ovary, mouse epitheloid C127,
      and pig kidney epithelial LLCPK1 cells producing high levels of functional
      recombinant human cystic fibrosis transmembrane conductance regulator (CFTR).
      Processing of CFTR to the mature and fully glycosylated form in these cells is
      inefficient with only approximately 40% of all newly synthesized CFTR being
      converted to the mature form. Furthermore, expression of the most frequent mutant
      allele of the cystic fibrosis (CF) gene, the delta F508 mutant in these
      epithelial cells, indicated that it is biosynthetically arrested at the
      endoplasmic reticulum and fails to traffic to the plasma membrane. Using a
      combination of CFTR mutants and monoclonal antibodies, all the detectable
      recombinant CFTR in these cells was determined at least under the conditions
      used, to be present as a monomer. To demonstrate the feasibility of protein
      replacement therapy, we were able to effect the physical transfer of functional
      recombinant CFTR produced in Chinese hamster ovary cells to the plasma membranes
      of Ha3b fibroblasts, a cell line devoid of cAMP-stimulated chloride channels.
      Transfer of CFTR was mediated by the hemagglutinin viral fusion protein of
      influenza virus present on the Ha3b cells. Efficiency of transfer was up to 25%
      of the target cells, and CFTR chloride channel activity was detectable for up to
      12 h post-fusion. Therefore, with the development of an appropriate formulation
      of fusogenic proteoliposome or virosome containing reconstituted purified CFTR,
      it should be feasible to introduce functional CFTR into CF-affected cells.

PMID- 7507933
TI  - Adjunctive interventions for burn pain control: comparison of hypnosis and
      ativan: the 1993 Clinical Research Award.
AB  - Thirty-two patients hospitalized for the care of major burns were randomly
      assigned to groups that received hypnosis, lorazepam, hypnosis with lorazepam, or
      placebo controls as adjuncts to opioids for the control of pain during dressing
      changes. Analysis of scores on the Visual Analogue Scale indicated that although
      pain during dressing changes decreased over consecutive days, assignment to the
      various treatment groups did not have a differential effect. This finding was in
      contrast to those of earlier studies and is likely attributable to the low
      baseline pain scores of subjects who participated. A larger number of subjects
      with low baseline pain ratings will likely be necessary to replicate earlier
      findings. The results are argued to support the analgesic advantages of early,
      aggressive opioid use via PCA or through careful staff monitoring and titration
      of pain drugs.

PMID- 7507934
TI  - New ultra-micro high-performance liquid chromatographic method for determining
      the gamma chain composition of hemoglobin F in normal adults.
AB  - The difficulty in isolating the minute quantity of Hb F (< 1%) present in the red
      blood cells of normal adults greatly complicates the determination of its gamma
      chain composition. We have developed a rapid ultra-micro high-performance liquid
      chromatographic (HPLC) method and used it to analyze the gamma chain composition
      of Hb F in 47 adults with Hb F levels between 0.1-3.4%. The method involves the
      isolation of Hb from as little as 50 microliters of whole blood on an analytical
      size cation-exchange HPLC column, followed by concentration in a Centricon micro
      concentrator unit and by reversed-phase HPLC analysis. The entire procedure can
      be completed in one day and 3-4 analyses can be made simultaneously. We
      reanalyzed the blood samples from 22 subjects with known beta-globin gene cluster
      haplotypes, and confirmed the association of high, low, and very low G gamma
      levels with haplotypes A, B, and C, respectively. Also included are the results
      of DNA sequence analyses of the G gamma and beta promoters, and of the locus
      control-region hypersensitive site-2 (LCR-HS-2) of the beta-globin gene cluster
      in five subjects homozygous for haplotypes A, B or C; the data obtained failed to
      provide a satisfactory explanation for all the variations in the G gamma levels
      that have been observed.

PMID- 7507935
TI  - The regulatory role of tri-iodothyronine on the production of alpha-fetoprotein
      and albumin by mouse fetal liver cells.
AB  - The purpose of this study was to assess possible effects of tri-iodothyronine
      (T3) on the production of alpha fetoprotein (AFP) and albumin by mouse fetal
      liver cells. AFP from serum-free conditioned media of TIB73 mouse fetal liver
      cells was measured by immunoradiometric assay and albumin was measured by
      chromogenic assay. The expression of mRNAs was quantified by Northern blotting
      analysis. A marked inhibition of AFP secretion was found as well as an increase
      in albumin produced by T3 in a dose-dependent manner. The effects of T3 AFP and
      albumin secretion paralleled the effects of T3 on the steady-state expression of
      mRNAs encoding albumin and AFP. These data may point to a possible role of T3 in
      the transcriptional switch from AFP to albumin during fetal development and may
      explain the observation of high levels of AFP in cases of congenital
      hypothyroidism.

PMID- 7507936
TI  - Blocking of human fertilization by carbohydrates.
AB  - The zona penetration test and triple stain technique were used to elucidate the
      blocking effects of carbohydrates on human fertilization and their mechanisms. In
      the presence of D-mannose or D-fructose (final concentration, 50 mmol/l), sperm
      penetration through the human zona pellucida was completely blocked. The triple
      stain technique revealed that D-fructose (50 mmol/l) significantly (P < 0.01)
      suppressed the acrosome reaction of human spermatozoa, while D-mannose did not
      show a suppressive effect on the acrosome reaction. These results reinforce our
      hypothesis proposed previously, that a mandatory step in human fertilization is
      the binding of a D-mannose-binding constituent of the sperm surface to a D
      mannose residue in the sperm receptor site on the zona pellucida. In addition, D
      fructose may play an important role as an acrosome stabilizing factor in seminal
      fluid.

PMID- 7507937
TI  - Sephadex filtration and human serum albumin gradients do not select spermatozoa
      by sex chromosome: a fluorescent in-situ hybridization study.
AB  - Fluorescent in-situ hybridization (FISH) of decondensed sperm nuclei has been
      used directly to evaluate the enrichment efficiency of human sperm separation
      using Sephadex gel filtration and human serum albumin (HSA) gradients. Control
      and processed spermatozoa were fixed and their nuclei decondensed. In-situ
      hybridization was carried out with a Y-specific DNA probe (DYZ1). Sephadex
      filtration yielded 52.5% Y-chromosome-bearing spermatozoa, HSA separation
      resulted in 49.4% Y-chromosome-bearing spermatozoa and in the untreated control
      sample the percentage of Y spermatozoa was 49.3%. Statistical analysis revealed
      no significant differences between the selection methods employed and the
      controls, and no real enrichment for X- or Y-bearing spermatozoa was detected for
      any of the selection methods assayed. The usefulness of the protocols reported
      for selection of spermatozoa by sex chromosome in couples at risk for X-linked
      diseases is discussed.

PMID- 7507938
TI  - Nebulin is a full-length template of actin filaments in the skeletal muscle
      sarcomere: an immunoelectron microscopic study of its orientation and span with
      site-specific monoclonal antibodies.
AB  - Nebulin, a giant myofibrillar protein with size variants from 700 to 900 kDa in
      various skeletal muscles, has been proposed to constitute a set of inextensible
      filaments anchored at the Z-line and coextensive with actin filaments. To
      elucidate the architectural organization of this fourth set of myofilaments in
      the skeletal muscle sarcomere, we performed immunoelectron microscopic
      localization of epitope profiles of a number of site-specific monoclonal
      antibodies against cloned human nebulin fragments of known sequence loci.
      Monoclonal antibody N113, which is directed to fragment ND8 at approximately 300
      residues away from the C-terminus, labelled the edges of Z-lines in both human
      quadriceps muscle and rabbit psoas muscle. Monoclonal antibody N101, which is
      directed to fragment NB5 near the N-terminal side, is localized to a single locus
      at 0.89 micron from the Z-line in human quadriceps muscle and 0.80 micron from
      the Z-line in rabbit psoas muscle. Additionally, monoclonal antibody N109, which
      is directed to fragment NA3 on the carboxy side of the adjacent fragment NB5, is
      localized at 0.76 micron away from the Z-line in rabbit psoas muscle. This one-to
      one correspondence between epitope loci and sequence loci demonstrates that a
      single nebulin polypeptide spans the length of the thin filament with its C
      terminus anchored at the Z-line. The epitope spacings of site-specific antibodies
      are consistent with the notion that the nebulin filament is uniform in mass
      density along its length.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507939
TI  - Induction of autologous mixed lymphocyte culture responses by myelin basic
      protein-reactive T cell clones.
AB  - Myelin basic protein is an autoantigen present in the central nervous system
      suspected to be the target of destruction in multiple sclerosis. In the present
      study, we have demonstrated that T cell clones specific for myelin basic protein
      have the ability to induce proliferative responses in resting T lymphocytes in
      the autologous mixed lymphocyte culture (AMLC). T cell recognition of the AMLC
      stimulatory determinants on the clones required the presence of autologous
      monocytes. T lymphocytes primed against an autologous myelin basic protein
      specific T cell clone displayed specific memory responses against the original
      stimulating clone and failed to exhibit secondary reactivity to 'sister' myelin
      basic protein-reactive clones and to autologous T cell clones specific for
      another antigen. Monoclonal antibodies specific for class II HLA-DR antigens
      inhibited secondary AMLC responses. Modulation of the T cell receptor from the
      surface of the clones decreased their AMLC stimulatory ability. These results
      indicate that idiotype-like determinants on the T cell receptor of autoantigen
      specific T cell clones are capable of triggering anti-idiotypic T cell responses.

PMID- 7507940
TI  - Corticocortical connections of area F3 (SMA-proper) and area F6 (pre-SMA) in the
      macaque monkey.
AB  - The monkey mesial area 6 comprises two distinct cytoarchitectonic areas: F3
      [supplementary motor area properly defined (SMA-proper)], located caudally, and
      F6 (pre-SMA), located rostrally. The aim of the present study was to describe the
      corticocortical connections of these two areas. To this purpose restricted
      injections of neuronal tracers (wheat germ-agglutinin conjugated to horseradish
      peroxidase, fluorescent tracers) were made in different somatotopic fields of F3,
      F6, and F1 (area 4) and their transport plotted. The results showed that F3 and
      F6 differ markedly in their cortical connections. F3 is richly linked with F1 and
      the posterior premotor and cingulate areas (F2, F4, 24d). Connections with the
      anterior premotor and cingulate areas (F6, F7, F5, 24c) although present, are
      relatively modest. There is no input from the prefrontal lobe. F3 is also
      connected with several postrolandic cortical areas. These connections are with
      areas PC, PE, and PEa in the superior parietal lobule, cingulate areas 23 and
      PEci, the opercular parietal areas (PFop, PGop, SII) and the granular insula. F6
      receives a rich input from the anterior premotor areas (especially F5) and
      cingulate area 24c, whereas its input from the posterior premotor and cingulate
      areas is very weak. A strong input originates from area 46. There are no
      connections with F1. The connections with the postrolandic areas are extremely
      meagre. They are with areas PG and PFG in the inferior parietal lobule, the
      disgranular insula, and the superior temporal sulcus. A further result was the
      demonstration of a differential connectivity pattern of the cingulate areas 24d
      and 24c. Area 24d is strongly linked with F1 and F3, whereas area 24c is
      connected mostly with F6. The present data support the notion that the classical
      SMA comprises two functionally distinct areas. They suggest that F6 (the rostral
      area) is responsible for the "SMA" so-called high level motor functions, whereas
      F3 (the caudal area) is more closely related to movement execution.

PMID- 7507941
TI  - Cerebellar influences on accessory oculomotor nuclei of the rat: a
      neuroanatomical, immunohistochemical, and electrophysiological study.
AB  - With the aim to evaluate a possible neocerebellar control on eye movements, the
      projections from the cerebellar lateral nucleus (LN) to the accessory oculomotor
      nuclei (i.e., the nucleus of posterior commissure, the nucleus of Darkschewitsch,
      and the interstitial nucleus of Cajal), the putative neurotransmitters subserving
      this pathway, and the nature of the synaptic influences exerted by these
      projections were studied in adult rats. We used the orthograde transport of
      horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) to
      identify the mesencephalic areas where cerebellofugal fibers terminate, and
      retrograde labeling with the fluorescent dye fluoro-gold to estimate the
      incidence of cerebellar neurons projecting to the accessory oculomotor nuclei.
      Orthograde labeling showed that only a small contingent of cerebellofugal fibers
      reaches the contralateral accessory oculomotor nuclei. The retrogradely labeled
      cells were located primarily in the small-celled part of LN. By
      immunohistochemistry, we observed that all the cells retrogradely labeled from
      the accessory oculomotor area were also stained by using glutamate or aspartate
      antisera, but none of them were double-stained with a GABA antiserum. Electrical
      stimulation of the contralateral LN elicited changes in firing rate of a
      significant fraction of cells belonging to the accessory oculomotor nuclei (36.4%
      in the nucleus of posterior commissure, 47.1% in the nucleus of Darkschewitsch,
      and 44.6% in the interstitial nucleus of Cajal). In 57.8% of the cases, the
      responses were excitations, most of which had latencies and response
      characteristics compatible with a monosynaptic linkage. The remaining 42.2% of
      the cases were inhibitions with latencies ranging between 5 and 22 ms.
      Extracellular field potential recordings within the contralateral accessory
      oculomotor nuclei were interpreted as arising from impulses propagating along
      excitatory axons projecting in a bundle from the cerebellum. Stimulation of LN
      area in rats following intranuclear injection of kainic acid was not capable of
      evoking short latency excitations, so these responses can be considered to depend
      on the activation of LN efferents. The LN projection on accessory oculomotor
      nuclei could be part of the final precise control exerted by the neocerebellum on
      those brain structures concerned with movements of the eyes.

PMID- 7507942
TI  - Auditory brainstem of the ferret: long survival following cochlear removal
      progressively changes projections from the cochlear nucleus to the inferior
      colliculus.
AB  - Some effects on auditory brainstem connections of long (1-2.3 years) survival
      following unilateral cochlear removal in infant and adolescent ferrets were
      examined by making multiple injections of wheat germ agglutinin conjugated to
      horseradish peroxidase (WGA-HRP) in either the left or the right inferior
      colliculus (IC). Previous studies have shown that, in normal adult ferrets, about
      50 times as many cochlear nucleus (CN) neurons project to the contralateral as to
      the ipsilateral IC. Right cochlear removal at P25 increased, within 30 days, the
      number of retrogradely labeled left CN neurons projecting to the left ipsilateral
      IC by 17% (from n = 235 to n = 275), relative to normals. In this study, longer
      survival (3 months to 1 year) after right cochlear removal at P25 resulted in
      larger increases (38-47%; n = 100) in the number of neurons labeled in the left
      CN after injections of WGA-HRP in the left IC. No change occurred in the number
      of neurons labeled in the right CN. Taken together, the results of these
      experiments show that the ratio of the number of labeled neurons in the left CN
      to that in the right CN increases progressively with survival time out to the
      maximum time tested (1 year). In contrast to these results, we have previously
      reported that right cochlear removal at P90 did not change the number of neurons
      projecting from the left CN to the left IC after 90 days of survival. However, in
      this study, very long survival (2.3 years) following right cochlear removal at
      P90 resulted in an increased (51%, from n = 235 to n = 355) number of left CN
      neurons labeled by WGA-HRP injections into the left IC, relative to normals. The
      increased number of labeled neurons included neurons throughout each division of
      the CN and all of the principal morphological types. In a separate series of
      experiments involving long survival (1-2 years), right cochlear removal at P25 or
      P40 did not significantly change the number of neurons in either CN retrogradely
      labeled by injections of WGA-HRP in the right IC, or the ratio between the number
      of neurons labeled in each CN. Long survival following cochlear removal at P25
      P90 did not result in any loss of neurons in the ipsilateral CN or in any
      shrinkage of CN neurons further than the 10-20% seen at a shorter survival time
      (90 days).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7507943
TI  - Cutaneous plexiform schwannoma in a pig.
AB  - A plexiform schwannoma (PFS) observed as a solitary mass in the dermis of a 6
      month-old pig consisted of schwannoma cells of Antoni A type and B type.
      Neoplastic cells in Antoni A type areas sometimes showed cord-like outgrowths or
      a neurofibromatous pattern. Neoplastic cells in Antoni B type areas showed
      erythrophagocytosis, some encircling the microvasculature. Immunohistochemically,
      neoplastic cells were strongly positive for S-100 protein and vimentin.
      Peripheral parts of the nodules were cytokeratin (clone AE1/AE3)-positive, as in
      normal swine perineurial cells. Double immunostaining clearly demonstrated
      neoplastic cells doubly positive for both S-100 protein and cytokeratin,
      suggesting that S-100-positive Schwann cells and cytokeratin-positive perineurial
      cells are functional variants of the same cell type. Ultrastructurally,
      neoplastic cells in Antoni A type areas possessed characteristics of Schwann
      cells, such as cytoplasmic interdigitation, external laminae and intercellular
      junctions. At the periphery of the nodules, features of perineurial cells were
      detected. Neoplastic cells in Antoni B type areas seemed to be undergoing
      degenerative processes similar to those in Antoni A type regions and they
      contained many lysosomes. The neoplasm was generally similar in both location and
      histology to that seen in man, but there were some histological,
      immunohistochemical and ultrastructural differences. This is the first reported
      case of PFS in domestic animals.

PMID- 7507944
TI  - Expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) during
      melanoma-induced angiogenesis in vivo.
AB  - Recent ultrastructural data indicate that tumor-induced angiogenesis involves
      polarized outgrowth of endothelial cells from established vessels into tumor
      parenchyma and interstitium. Efforts to define the cytoarchitecture of the
      angiogenic response and to ascertain molecular determinants of polarized
      endothelial migration have been impeded by lack of sensitive and specific
      immunologic markers for endothelium and vessel wall components. In this study, we
      utilized monoclonal antibody to platelet-endothelial cell adhesion molecule-1
      (PECAM-1), a cell-cell adhesion molecule belonging to the immunoglobulin
      superfamily, to determine extent and patterns of angiogenesis in metastatic
      melanomas before (N = 7) and after (N = 3) induction of tumor-infiltrating
      lymphocyte responses provoked by administration of experimental melanoma vaccine.
      PECAM-1 proved to be a more reliable marker for angiogenesis than antibodies to
      von Willebrand Factor. Although both normal and tumor vessels exhibited prominent
      staining for PECAM-1, different patterns of endothelial reactivity were observed.
      Formation of new vessels was associated with i) PECAM-1 redistribution from a
      constitutive circumferential membrane pattern to a pattern restricted to cell
      cell junctions; ii) formation of endothelial cords formed by cell-cell
      interactions; and iii) eventual development of open lumens. Vessels within
      inflamed (vaccine-treated) and non-inflamed melanomas did not differ with regard
      to patterns of PECAM-1 expression. Forming vessels of inflamed melanomas failed
      to express the cytokine-inducible activation marker, E-selectin. Although normal
      microvessels and reactive vessels of healing wounds demonstrated prominent
      staining for alpha 6 laminin receptor, vessels within melanomas showed apparently
      diminished expression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507945
TI  - Proliferating cell nuclear antigen distribution in keratoacanthoma and squamous
      cell carcinoma.
AB  - Histologic differentiation of keratoacanthoma (KA) and squamous cell carcinoma
      (SCC) is often difficult despite well-delineated histopathologic criteria. This
      has prompted a search for more objective methods to differentiate these two
      lesions. In the present study, we immunohistochemically examined the distribution
      of proliferating cell nuclear antigen (PCNA)-positive cells in 11 cases of KA, 7
      cutaneous SCC, and 2 atypical squamous proliferations (for which a definitive
      diagnosis could not be made on routine histology) using a commercially prepared
      anti-PCNA monoclonal antibody. We found PCNA-positive cells predominantly in the
      periphery of squamous nests in KA. In contrast, SCC showed a diffuse staining
      pattern with PCNA-positive cells seen throughout squamous nests. Determining the
      pattern of PCNA-positive cells is easy, does not require cell counting, and may
      provide additional histochemical data facilitating the distinction between KA and
      SCC.

PMID- 7507946
TI  - p53 protein in aggressive and non-aggressive basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the most frequent cutaneous neoplasm, with a
      generally favorable clinical behavior. Sometimes, indeed, it recurs after therapy
      and/or metastasizes. As point mutations in the coding sequence of the p53 tumor
      suppressor gene have been implicated in the progression of many human tumors, we
      studied the expression of p53 protein on this neoplasia. We tested
      immunohistochemically the positivity for p53 protein (NCL-p53-CM1, YLEM) on 19
      cases of morphologically "non aggressive" BCC (BCC1) and on 19 "aggressive" BCC
      (BCC2), all with one or more relapses and 3 with distant metastases also. Results
      were related to clinico-pathological and follow-up data. All but one BCC2 were
      found positive for p53 protein. Conversely, only 2 cases of BCC1 exhibited low
      immunoreactivity for p53 protein, with high statistical differences between the
      two groups. No correlation was found between the immunoreactivity, age of
      patients, and site of the lesions. The availability of immunohistochemistry and
      the relatively easy interpretation of the results make screening for p53 protein
      a possibly useful tool in the prognostic evaluation of BCC.

PMID- 7507947
TI  - Immunophenotypic analysis suggests that granuloma faciale is a gamma-interferon
      mediated process.
AB  - Granuloma faciale (GF) is an uncommon inflammatory dermatosis with characteristic
      clinical and histologic features. Very little is known about its pathogenesis. We
      used a battery of immunoperoxidase lymphocyte markers to study the population of
      hematopoietic cells present in a case of GF. The majority of non-myelocytic
      hematopoietic cells present were T-helper lymphocytes. The cells stained strongly
      with antibodies against the interleukin-2 receptor and with anti-lymphocyte
      functional antigen (LFA 1 alpha) antibodies. Overlying keratinocytes did not
      stain with ICAM-1 or HLA-DR, which may account for the presence of the Grenz zone
      in granuloma faciale. These findings suggest that a gamma-interferon-mediated
      process may play some role in the pathogenesis of this disorder.

PMID- 7507948
TI  - Friday evening slide symposium.

PMID- 7507949
TI  - The effect of continuous corticosterone administration on lymphocyte
      subpopulations in the peripheral blood of the Fischer 344 rat as determined by
      two color flow cytometric analyses.
AB  - This study was undertaken to determine the effects of continuous corticosterone
      administration on lymphocyte subsets in the peripheral blood of Fischer 344 rats.
      Pellets which released corticosterone over a 21 day period (0.07 mg/day, 0.48
      mg/day and 4.8 mg/day) were implanted subcutaneously in male rats. Control rats
      received pellets containing only the excipient carrier. Rats in the test and
      control groups were sacrificed at 7, 14 and 21 days. Lymphocyte subsets were
      enumerated by dual color flow cytometry and the data expressed in absolute
      numbers/mm3. Effects were observed only in the animals treated with the highest
      dose which was 70,000 times the normal plasma level. The spleen, thymus and lymph
      nodes were examined for histopathological changes. At the seven day sacrifice
      there was a statistically significant decrease in total white blood cells and
      selective decrements in lymphocytes with reductions in the absolute numbers of
      the T helper/amplifier, T cytotoxic/suppressor and B cells. Only numbers of
      natural killer cells were within normal limits. Histopathological data from
      animals treated with the high dose corticosterone for seven days demonstrated
      decreased thymic weights and a loss of thymic lymphocytes. At 14 and 21 days, the
      numbers of lymphocytes returned to the normal range, but the numbers of total T
      cells remained decreased. Also, thymic weights were reduced but not histological
      abnormalities were observed in the thymus. The data suggest that corticosterone
      induced a persistent decrease in total T cells, but only a transient effect on
      total lymphocytes.

PMID- 7507950
TI  - Identification of connective tissue gene transcripts in freshly isolated
      parenchymal, endothelial, Kupffer and fat-storing cells by northern hybridization
      analysis.
AB  - The aim of the present study was to identify the cell types that express collagen
      alpha 1(I), alpha 1(III) and alpha 1(IV), fibronectin and laminin B1 genes in
      normal rat liver. Parenchymal, sinusoidal endothelial, Kupffer and fat-storing
      (Ito) cells were isolated and purified. Total RNA of the freshly isolated cells
      was subjected to Northern hybridization analysis. We also compared the steady
      state levels of specific mRNAs in freshly isolated fat-storing cells to the
      levels in myofibroblast-like cells obtained from purified fat-storing cells
      cultured for two passages. The average purity of each cell preparation, and the
      percentage of contaminating cells, were determined by transmission electron
      microscopy and by examining the presence of vitamin A-autofluorescent cells.
      Fibronectin and collagen alpha 1(III) mRNAs were detected in total RNA of
      purified parenchymal cells. In poly(A)+ enriched RNA, small amounts of collagen
      alpha 1(I) mRNA were also present. In total RNA of freshly isolated fat-storing
      cells, collagen alpha 1(III), alpha 1(IV), and laminin B1 transcripts were found,
      whereas collagen alpha 1(I) and fibronectin mRNAs were not detected. Cultured fat
      storing cells, however, did contain high levels of collagen alpha 1(I) and
      fibronectin mRNAs. The molecular size of the latter transcript was larger than
      the fibronectin transcript found in parenchymal cells and the whole liver.
      Endothelial cells contained small amounts of alpha 1(IV) mRNA. Kupffer cells did
      not contain the investigated transcripts. We conclude that normal parenchymal,
      fat-storing and endothelial cells each express a typical pattern of connective
      tissue molecules. When fat-storing cells are allowed to differentiate into
      myofibroblast-like cells, they express high levels of collagen alpha 1(I) and
      fibronectin mRNAs, in addition to collagen alpha 1(III) and alpha 1(IV), and
      laminin B1 chain mRNAs.

PMID- 7507952
TI  - Limitations of serological assays for hepatitis C virus screening in blood
      donors.

PMID- 7507951
TI  - Chronic non-B, non-C hepatitis among blood donors assessed with HCV third
      generation tests and polymerase chain reaction.
AB  - Forty five blood donors with increased serum aminotransferases levels had liver
      histologic assessment and were tested for antibodies to hepatitis C virus (anti
      HCV) with second and third generation ELISAs and RIBAs, and for HCV RNA with
      polymerase chain reaction (PCR) in serum and liver tissue. Twenty-nine of these
      45 donors (65%) had steatosis without chronic hepatitis. Sixteen (35%) had
      chronic hepatitis. Twelve had evidence of HCV infection. Four had no evidence of
      HCV infection demonstrable by ELISA, RIBA or PCR. These four patients had no
      known cause of chronic hepatitis and no risk factor for parenterally acquired
      viral infection was found in them. This observation supports the hypothesis that
      a non-B, non-C virus might be implicated in chronic hepatitis. However, this
      hypothesis remains to be demonstrated.

PMID- 7507953
TI  - Long-term persistence of IgM antibodies to HCV in chronic hepatitis C.

PMID- 7507954
TI  - The common pattern of cytokeratin alteration in alcoholic and cholestatic liver
      disease is different from that of hepatitic liver damage. A study with the
      panepithelial monoclonal antibody lu-5.
AB  - The patterns of cytokeratin as determined by murine monoclonal antikeratin
      antibody lu-5 (mAb lu-5) were quantitated in paraffin-embedded liver tissue from
      normal and diseased subjects. In tissue from healthy medical students, mAb lu-5
      was found to decorate 2-4 periportal and 2-3 perivenular cell layers. Alcoholic
      liver disease was accompanied by a marked increase in intensity of mAb lu-5
      antigen expression in zone I and III hepatocytes. Moreover, additional liver
      cells of both zones were progressively recruited, so that in advanced lesions all
      three lobular zones became positive. In mechanical as well as in drug-induced
      cholestasis, a similar increase of mAb lu-5 antigen expression was already
      observed in earlier stages of disease, including an earlier recruitment of zone
      II hepatocytes. In both alcoholic and cholestatic biopsies the intensity and
      extent of mAb lu-5 epitope expression increased with the duration and severity of
      disease. In primary biliary cirrhosis (PBC) and seemingly also in primary
      sclerosing cholangitis the increase and extent was more marked in zone I, the
      zone of assumed cholate accumulation. Changes in zone III, the territory of
      histologic cholestasis (bilirubinostasis), became evident only in late stages of
      PBC. Mallory bodies of alcoholic and cholestatic liver disease showed an
      identical mAB lu-5 antigen expression, thus giving rise to four different
      staining patterns. Changes of cytokeratin expression are similar in alcoholic and
      cholestatic liver diseases. In chronic viral hepatitis, however, cytokeratin
      alterations are discrete and restricted to precirrhotic/cirrhotic stages.

PMID- 7507955
TI  - Production of human cloned antibodies specific for hepatitis D virus-encoded
      small and large protein.
AB  - Cloned antibodies to specific epitopes of hepatitis D virus were produced by
      transformation with Epstein-Barr virus and subsequent cloning of peripheral blood
      B lymphocytes from a patient with chronic hepatitis D virus infection. Several
      stable cloned B cell lines, derived from two parent cultures, produced hepatitis
      D-virus-specific IgG antibodies. Some cloned IgG antibodies detected hepatitis D
      virus-associated antigen in hepatitis D virus-infected woodchuck liver tissue
      sections by indirect immunofluorescence staining and some reacted in an
      inhibition ELISA test detecting hepatitis D virus antibodies; most cloned IgG
      lines detected hepatitis D antigen both in immunofluorescence tests and in
      inhibition ELISA. Cloned antibodies to hepatitis D antigen detected by ELISA
      and/or immunofluorescence staining recognized the two major specific native and
      denatured polypeptides, p27 and p29, in Western blot analysis. Such cloned
      antibodies for hepatitis D virus are potentially useful for clinical diagnosis
      and research.

PMID- 7507956
TI  - Cytotoxic lymphocyte granzymes trigger a target cell internal disintegration
      pathway leading to cytolysis and DNA breakdown.
AB  - Two approaches have been used to assess the hypothesis that granzymes secreted by
      cytotoxic lymphocytes act within the target cells to trigger an internal
      disintegration pathway leading to target cell lysis. The lytic properties of
      several clones of rat basophilic leukemia cells transfected with either cytolysin
      (perforin) alone (RBL-cy) or a combination of cytolysin and granzyme A (RBL-cy
      gza) were compared with cloned CTL. Analysis of the kinetics of target cell 125I
      DNA vs 51Cr release with three tumor targets showed negligible DNA release with
      RBL-cy, less extensive 125I-DNA release relative to 51Cr release with RBL-cy-gza
      effector cells, whereas CTL caused greater or equal DNA release than 51Cr release
      at all time points. Using three different tumor target cells, comparison of RBL
      cy-gza and RBL-cy clones in multiple experiments shows that RBL-cy-gza are on
      average more than threefold more lytic than RBL-cy. This distinction was not seen
      with red cell targets, in which an internal disintegration pathway does not
      operate. A second approach to this issue consisted of cytoplasmic loading of
      tumor target cells with aprotinin, a macromolecular protease inhibitor known to
      inhibit granzyme A and probably other granzymes. Although the control BSA-loaded
      target cells were essentially identical to nonloaded targets in all cases,
      aprotinin-loaded targets showed substantially lower release of both 51Cr and 125I
      DNA with both CTL and RBL-cy-gza effector cells. In contrast, aprotinin-loaded
      targets were lysed with the same efficiency as control targets by RBL-cy effector
      cells. We conclude that secreted granzymes contribute to target lysis by
      triggering a target cell internal disintegration pathway that leads to both lysis
      and DNA breakdown.

PMID- 7507957
TI  - Redox mechanism as alternative to ligand binding for receptor activation
      delivering disregulated cellular signals.
AB  - Cross-linking with specific ligand is a general requirement for ordered
      activation of cell surface receptors. In this study we demonstrated a novel
      pathway for disregulated receptor activation through a redox mechanism. Treatment
      of murine thymocytes or spleen cells with thiol-reactive HgCl2, a known inducer
      of autoimmune proliferative lymphocyte disorders in rodents, was found to induce
      tyrosine phosphorylation of several cellular proteins, which was up to 100 times
      as extensive as that triggered by stimulation with antireceptor antibody or
      mitogen. Through the cross-linkage by thiol-reactive bivalent mercury,
      transmembrane CD4, CD3, and CD45 and glycosylphosphatidylinositol-anchored Thy-1
      were aggregated together on thymocytes or T lymphocytes. Along with the
      aggregation of Thy-1 and CD4, nonreceptor protein tyrosine kinase p56lck was
      aggregated and activated. These events were linked to extensive protein tyrosine
      phosphorylation, which was visualized as a well localized spot beneath the
      membrane. Under appropriate conditions, this novel pathway of multiple receptor
      aggregation delivered a disregulated signal into T lymphocytes, which cross
      talked to the antireceptor antibody-induced signal, for prolonged cell
      proliferation and IL-2 production. These results suggest a novel mechanism of
      disregulation of the ligand-dependent receptor function.

PMID- 7507958
TI  - IL-13 induces proliferation, Ig isotype switching, and Ig synthesis by immature
      human fetal B cells.
AB  - In this study it is demonstrated that the novel T cell-derived cytokine IL-13
      induces proliferation, Ig isotype switching, and Ig synthesis by human immature B
      cells derived from fetal bone marrow (BM). IL-13 induced proliferation and IgM,
      total IgG, IgG4, and IgE synthesis when total fetal BM cells or highly purified s
      mu+, CD10+, CD19+ fetal B cells were cultured in the presence of anti-CD40 mAb or
      activated CD4+ T cells. Although the ratios of the different isotypes produced in
      response to IL-13 were similar to those induced by IL-4, the levels of Ig
      produced in response to IL-13 were generally 5- to 15-fold lower, indicating that
      IL-13 is less potent than IL-4. In addition, in co-cultures of fetal B cells and
      CD4+ T cell clones IL-13 was effective only in the presence of IL-7, which may be
      due to the fact that IL-13, in contrast to IL-4, does not act on T cells. IL-13-
      and IL-4-induced IgE synthesis by s mu+, CD19+ fetal B cells was enhanced by IL-6
      and inhibited by IL-12, IFN-alpha, IFN-gamma, and transforming growth factor
      beta, suggesting that IL-13 and IL-4 induce IgE synthesis via similar signaling
      pathways. Like IL-4, IL-13 also induced Ig production, including IgG4 and IgE
      synthesis, by highly purified s mu-, CD10+, CD19+ pre-B cells co-cultured in the
      presence of activated cloned CD4+ T cells and IL-7. However, in contrast to IL-4,
      IL-13 did not enhance CD23, CD40, and HLA-DR expression on cultured s mu- pre-B
      cells in the absence of other stimuli, suggesting that IL-13 alone does not
      activate pre-B cells. Taken together, our data indicate that IL-13 induces
      proliferation, Ig isotype switching, and Ig production by immature fetal B cells
      in the presence of costimulatory signals provided by activated CD4+ T cells or
      anti-CD40 mAb. IL-13 is another cytokine that, in addition to IL-4, can induce
      isotype switching to IgG4 and IgE synthesis in immature human B cells.

PMID- 7507959
TI  - Tissue-specific regulation of IL-4 mRNA expression in human tonsil.
AB  - The cellular and molecular regulation of IL-4 mRNA expression in human tonsillar
      T lymphocytes was examined to define the mechanisms responsible for biphasic IL-4
      mRNA expression in this lymphoid organ. Tonsillar T cells expressed IL-4 mRNA in
      a biphasic manner with peaks at 8 and 24 h after PHA stimulation. De novo protein
      synthesis was not required for IL-4 mRNA expression because cycloheximide
      treatment of tonsillar MNC did not ablate the response. Nuclear runoff assays
      demonstrated transcription of the IL-4 gene at 8 and 24 h, which was not affected
      by addition of actinomycin D. Separation of T cells into naive (CD45RAhi/CD29lo)
      and primed (CD45RAlo/CD29hi) subpopulations revealed that although naive and
      primed T cells expressed IL-4 mRNA at 8 h, the 24-h peak of IL-4 mRNA expression
      was solely due to primed (CD45RAlo/CD29hi) Th cells. This effect was tissue
      specific and IL specific in that 1) primed peripheral blood T cells had only one
      peak of IL-4 mRNA expression at 8 h and 2) in primed tonsillar T cells, mRNA
      expression of IL-2, IL-6 and IL-2 receptor and c-myc was not delayed. Thus, IL-4
      mRNA expression in the tonsil differs depending on the surface expression of
      different isoforms of the leukocyte common Ag. The tissue- and stimulus-specific
      regulation of IL-4 mRNA in different lymphoid tissues may play an important role
      in regional immunoregulation.

PMID- 7507960
TI  - Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity.
AB  - Activation of the Fas cell surface molecule, either by specific antibody or by
      its as yet unidentified ligand, has been shown to induce apoptosis. Because
      apoptosis is also evoked in target cells by cytolytic T cells, we investigated
      whether the Fas pathway is involved in CD4+ T cell-mediated cytotoxicity.
      Analysis of Fas expression in APC, such as the B lymphoma A20.2J and MHC class II
      transfected fibroblasts RT2.3, revealed a correlation between the degree of
      expression and sensitivity to cytotoxic attack, high level of Fas expression in
      A20.2J being associated with efficient lysis. To examine whether increased Fas
      expression in RT2.3 would render these cells more susceptible to CD4+ CTL lysis,
      they were transfected with a Fas gene expression vector. Indeed, Fas- but not
      mock-transfected RT2.3 proved to be more sensitive to lysis by either Ag
      specifically or nonspecifically activated CD4+ CTL. Similarly, MHC class II
      negative, Fas-transfected L1210 leukemia cells were lysed with nonspecifically
      activated CD4+ CTL. The importance of the Fas engagement in CD4+ CTL-mediated
      cytotoxicity is further substantiated by the failure of both cloned and normal
      CD4+ CTL to lyse B cell blasts from Ipr mice. These mice are known to have a
      defect in functional Fas expression. Although the bulk of CD4+ T cell-mediated
      lysis appears to be Fas induced, the fact that the effector phase of A20.2J lysis
      is only partially Ca2+ independent indicates that other pathways also contribute
      to target cell death.

PMID- 7507961
TI  - Cloning, genomic organization, and chromosomal localization of the Scya5 gene
      encoding the murine chemokine RANTES.
AB  - RANTES is a member of the C-C subfamily of chemokines that functions as a
      proinflammatory chemoattractant for CD4+ T cells, monocytes, and eosinophils, and
      as an activator of basophils to release histamine. Like other members of the
      chemokine superfamily, RANTES has been implicated in a number of chronic
      inflammatory and autoimmune processes based on its function and its pattern of
      regulation. To begin study of the transcriptional regulation of RANTES, we have
      determined the genomic organization of the gene encoding the small inducible
      cytokine A5 (Scya5) and performed an initial analysis of its promoter elements.
      The Scya5 gene is located on chromosome 11. By Southern blot, it is a single-copy
      gene approximately 4.5 kb long composed of 3 exons. This chromosomal localization
      and pattern of genomic organization is conserved among the other C-C subfamily of
      chemokines. Primer extension analysis was used to identify the transcriptional
      initiation site that is located 27 bp downstream of a typical TATAA box. Sequence
      analysis of 1040 bp 5' to the start site of the Scya5 gene revealed a number of
      regulatory motifs that are also shared among the chemokine family including a
      PU.1 box, a NF-kappa B, and an IFN regulatory factor-1 response element. This
      region of genomic DNA was also cloned into a luciferase reporter vector.
      Transfection of this reporter construct into murine proximal tubular cells
      reveals that TNF-alpha can induce a transcriptional activation of the gene, as
      would be predicted from the rise in mRNA transcripts encoding RANTES in cells
      stimulated with TNF-alpha.

PMID- 7507962
TI  - Changes in cell adhesion molecule expression on T cells associated with systemic
      virus infection.
AB  - Virus-induced changes in adhesion molecule expression on T cells were
      investigated to understand how antiviral effector cells migrate into infectious
      foci. FACS analysis revealed that after systemic infection with lymphocytic
      choriomeningitis virus a number of cell adhesion molecules, including VLA-4, LFA
      1, and ICAM-1, are up-regulated on CD8+ cells, whereas the lymph node homing
      receptor MEL-14 is down-regulated during the infection; only marginal changes
      were observed for CD4+ cells. Basically similar but less marked results were
      obtained in mice infected with Pichinde virus. Further analyses showed that T
      cells with a changed adhesion molecule profile tended to present other cell
      surface markers indicating a state of cellular activation, e.g., IL-2R, and
      included all virus-specific CTL effectors. Regarding the physiologic significance
      of these changes in adhesion molecule expression, it was found that up-regulation
      of VLA-4 expression on splenic T cells correlated with influx of inflammatory
      cells into the cerebrospinal fluid of intracerebrally infected animals, and that
      the number of CD8+VLA-4hi cells increased from lymph nodes and spleen to blood
      and cerebrospinal fluid. These results support the hypothesis that up-regulation
      of VLA-4 is important for effector T cell homing to sites of inflammation.

PMID- 7507963
TI  - Metalloprotease and serine protease are involved in cleavage of CD43, CD44, and
      CD16 from stimulated human granulocytes. Induction of cleavage of L-selectin via
      CD16.
AB  - CD43, CD44, CD16, and L-selectin have been previously shown to be enzymatically
      cleaved from stimulated leukocytes. However, little is known about the enzymes
      involved in these processes. Here, metalloprotease(s) inhibitable by 1,10
      phenanthroline together with serine protease(s) inhibitable by N alpha-p-tosyl-L
      lysine chloromethyl ketone and 3,4-dichloroisocoumarin are shown to be involved
      in the cleavage of CD43, CD44, and CD16 but not in the cleavage of L-selectin on
      granulocytes. In addition, mAbs that recognize these individual receptors and
      induce their specific cleavage did not initiate cleavage of the others. In one
      case only, L-selectin, cleavage was also triggered by mAbs interacting with CD16
      (the low affinity Fc gamma R). Thus, this mechanism represents a novel pathway of
      L-selectin cleavage induction.

PMID- 7507965
TI  - A role for lectin interactions during human neutrophil aggregation.
AB  - We have recently reported that neutrophil aggregation is dependent on both L
      selectin and the beta 2-integrin Mac-1, raising the possibility that carbohydrate
      interactions play a role in aggregation. We used mono- and polysaccharides known
      to inhibit L-selectin-dependent adhesion of lymphocytes to high endothelial
      venules to test whether these carbohydrates could inhibit neutrophil aggregation.
      Similar types and concentrations of carbohydrates found by others to inhibit
      lymphocyte adhesion were effective in blocking neutrophil aggregation. Thus,
      nanomolar concentrations of the polysaccharides dextran sulfate (m.w. 500,000)
      and fucoidan inhibited aggregation, whereas dermatan sulfate, alpha-carrageenan,
      and dextran sulfate (m.w. 5,000) showed no inhibition. All of the phosphorylated
      monosaccharides tested inhibited aggregation with ED50 values between 8 and 17
      mM, the most potent being mannose-6-phosphate and fucose-1-phosphate. The
      nonphosphorylated monosaccharides glucose and fucose were noninhibitory. The
      inhibitory effects of fucoidan or dextran sulfate (m.w. 500,000) did not appear
      to be due to altered regulation of L-selectin after stimulation because fucoidan
      reduced the rate of L-selectin shedding, whereas dextran sulfate had no effect
      compared with control. Neither carbohydrate inhibited the binding of formyl
      peptide to its receptor. However, carbohydrates were able to compete with mAb
      binding to a number of known leukocyte adhesion proteins. We used endotoxin
      pretreatment to create L-selectin-deficient neutrophils to study the minimum
      adhesive requirements for aggregation using two-color fluorescence flow
      cytometry. Our results implicate a lectinlike contribution to neutrophil
      aggregation, and suggest that L-selectin is the molecule that mediates the
      carbohydrate-dependent adhesive event.

PMID- 7507964
TI  - Substance P increases neutrophil adhesion to bronchial epithelial cells.
AB  - Polymorphonuclear neutrophils (PMNs) accumulate within the airways during acute
      and chronic bronchitis and can adhere to bronchial epithelium. Substance P (SP),
      a neuropeptide released from the primary afferent nerve endings, has been shown
      to have a proinflammatory effect on PMNs. To test the hypothesis that SP could
      modulate PMN bronchial epithelial cell adherence, bovine bronchial epithelial
      cells (BBECs) were isolated and cultured, and the capacity of SP to modulate PMN
      BBEC adherence was evaluated. SP interacted with BBECs to induce an increase in
      PMN adhesion (14.7 +/- 1.2% vs 5.3 +/- 0.7% adherence, p < 0.01). The effect of
      SP was both time- and dose-dependent with maximal responses at 6 h and 10(-10) M.
      The effect was reproduced by the carboxyl-terminal sequence of the molecule (SP 6
      11). Importantly, pretreatment of the BBECs with the tachykinin SP receptor (NK1)
      antagonist, CP-96,345, significantly reduced the increase in adhesion induced by
      SP (p < 0.01). Furthermore, treatment of the BBECs with antibodies against CD11a
      (LFA-1), CD11b (MAC-1), or ICAM-1 significantly decreased SP-induced adherence (p
      < 0.01 all comparisons). Conversely, SP stimulation of PMN induced a dose
      dependent, rapid (within 5 min) increase in adherence. This effect was also
      mediated by the carboxy end of the molecule and was decreased by CP-96,345, again
      suggesting that this effect was NK1 mediated. These data demonstrate the SP has
      the capacity for modulating PMN-BBEC interactions and suggest an important role
      for SP in modulating airway inflammation.

PMID- 7507966
TI  - Decay-accelerating factor on human umbilical vein endothelial cells. Its
      histamine-induced expression and spontaneous rapid shedding from the cell
      surface.
AB  - Decay-accelerating factor (DAF) is a membrane protein that protects host cells
      from attack by its own complement. Although DAF expression on endothelial cells
      is thought to increase pathophysiologically, little is known about the natural
      mediators that modulate DAF expression on endothelial cells. In this study, we
      evaluated the effect of histamine on DAF expression on human umbilical vein cells
      (HUVEC). HUVEC were cultured with histamine, and DAF expression on HUVEC was
      determined by flow cytometry after immunostaining with a mAb to DAF. DAF
      expression on HUVEC was increased at 10 microM histamine, and the final level was
      increased time-dependently by 150% to 200% after a 24-h incubation with 100
      microM histamine. The histamine-induced DAF expression was inhibited by
      actinomycin D and cycloheximide and accompanied by an increase in the DAF mRNA
      level, indicating that both transcription and translation are required. In
      addition, the histamine-induced DAF expression was inhibited by pyrilamine, an H1
      blocker, but not by cimetidine, an H2 blocker, indicating that histamine induces
      the DAF expression through H1 receptors. We also demonstrated that the turnover
      of DAF is faster than that of MCP and CD59, and DAF is released into the culture
      supernatant. DAF is a glycosylphosphatidylinositol-linked protein that is
      released from HUVEC by a phosphatidylinositol-specific phospholipase C. Although
      HUVEC also contain the glycosylphosphatidylinositol-anchored complement inhibitor
      CD59, this was not released during a 24-h incubation, suggesting that the
      shedding of DAF from HUVEC is not caused by PI-PLC but by other enzymes, possibly
      proteinases. These results suggest that histamine, which is released from mast
      cells and basophils by complement-derived anaphylatoxins, increases the
      complement defense ability of endothelial cells by increasing their levels of DAF
      expression.

PMID- 7507967
TI  - Inhibition of activation-induced death in T cell hybridomas by thiol
      antioxidants: oxidative stress as a mediator of apoptosis.
AB  - N-Acetylcysteine (NAC) is a well established thiol antioxidant which, after
      uptake, deacylation and conversion to glutathione functions as both a redox
      buffer and a reactive oxygen intermediate scavenger. We report here that NAC
      completely blocks activation induced death and associated DNA fragmentation of
      myelin basic protein (MBP) specific T cell hybridomas. Conversely, NAC had very
      little effect on the antigen driven proliferation of a MBP specific T cell line
      similar to that from which the hybridomas were derived. NAC displayed an
      analogous absolute inhibition of mitogen mediated activation induced death, even
      if added up to 3 h post activation. Although glutathione was as efficient as NAC
      at blocking activation induced death, dithiothreitol displayed minimal inhibition
      while L-cysteine had no effect at all. The observation that certain thiol
      antioxidants such as NAC and glutathione can completely block the activation
      induced death of T cell hybridomas implicates redox regulation in this process.

PMID- 7507968
TI  - Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in
      primary mouse macrophages.
AB  - Nitric oxide (NO) contributes to the antitumor, antimicrobial, and
      immunosuppressive activity of macrophages. An inducible form of NO synthase
      (iNOS) is responsible for high output generation of nitric oxide by macrophages
      after stimulation with cytokines and/or lipopolysaccharide (LPS). In the present
      study, we demonstrate that interleukin 4 (IL-4) suppressed production of NO by
      primary mouse peritoneal macrophages exposed to IFN-gamma with or without LPS,
      even while synergizing with IFN-gamma to increase the secretion of TNF-alpha.
      Suppression of NO production was paralleled by decreases in iNOS enzyme activity
      and iNOS antigen. IL-4 did not inhibit induction of iNOS mRNA 4-6 h after
      exposure to IFN-gamma, but strongly reduced iNOS mRNA at later times of
      stimulation (24-72 h), without increasing its turnover. The conditions for
      maximal suppression of iNOS expression by IL-4 and the mechanisms of suppression
      differed from those determined in parallel for transforming growth-factor-beta as
      described elsewhere. These results illustrate the diversity of phenotypes of
      macrophages deactivated by different cytokines, and demonstrate that IL-4 has the
      potential to reduce one component of the anti-tumor, antimicrobial, and
      immunosuppressive activities of macrophages.

PMID- 7507970
TI  - The monoclonal antibody MAC387 detects an epitope on the calcium-binding protein
      MRP14.
AB  - The present study was initiated to identify the antigen recognized by the
      monoclonal antibody (MAb) MAC387 which is widely used for phenotypical
      characterization of myelomonocytic cells in situ. MAC387 has been described to
      show a similar reaction pattern as antisera to a complex formed by the calcium
      binding proteins MRP8 and MRP14. However, the exact nature of the molecule
      recognized by MAC387 has been controversial. Using Western blot analysis, MAC387
      was found to detect a single protein band of 14 kDa in lysates of human monocytes
      and granulocytes. Transfection of embryonic lung fibroblasts L132 with either
      MRP8 or MRP14 cDNA revealed that MAC387 reacts with MRP14 but not MRP8. This
      finding was confirmed by dot blot analysis of recombinant MRP8 and MRP14. Our
      data thus provide unequivocal evidence that MAC387 is a monoclonal antibody
      directed against the calcium-binding protein MRP14.

PMID- 7507971
TI  - Activation of macrophages for cytolysis of virally infected cells by monoclonal
      antibody to the 73-kDa lipopolysaccharide receptor.
AB  - The abilities of lipopolysaccharide (LPS) and mAb5D3 (a monoclonal antibody
      specific for the 73 kDa LPS receptor) to activate bone marrow culture derived
      macrophages (BMCM) for cytolysis of vesicular stomatitis virus infected BALB/c3T3
      (VSV-3T3) and the tumor target, P815, were compared. Activation for cytolysis of
      VSV-3T3 cells occurred at a lower level of either LPS or mAb5D3 than activation
      for cytolysis of P815. With both targets and under several stimulation conditions
      there was a constant differential between the two activating stimuli. These data
      indicate that stimulation of the 73 kDa LPS receptor at low levels of either
      mAb5D3 or LPS can activate BMCM for cytolysis of VSV-3T3 but not P815. Further,
      the constant relative efficiency of mAb5D3 to LPS in both target systems suggests
      that there is a common receptor for both LPS mediated effects.

PMID- 7507969
TI  - Cytokine induction in mice by the immunomodulator imiquimod.
AB  - Imiquimod has been identified as a potent antiviral and antitumor agent in animal
      models. The biological activity associated with imiquimod has been attributed to
      its induction of interferon (IFN)-alpha. The present studies evaluated imiquimod
      administered orally for its ability to stimulate production of IFN and other
      cytokines in mice. The cytokine profile induced by imiquimod was compared with
      other known immunomodulators. Imiquimod was found to stimulate increased serum
      IFN in mice. Daily dosing of imiquimod for five consecutive days led to
      diminished production of IFN in mice as measured after the final dose. Elevated
      levels of serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 but not
      IL-1 alpha were found in serum from mice treated with imiquimod. Imiquimod
      produced significantly higher levels of IFN but lower levels of TNF and IL-6 and
      IL-1 alpha than lipopolysaccharide. Polyinosinic acid:polycytidylic acid induced
      significantly higher amounts of IFN but lower levels of TNF and IL-6 than
      imiquimod. Imiquimod stimulated significantly higher levels of IFN when compared
      with 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) and similar levels of IFN
      when compared with tilorone. Neither ABPP nor tilorone induced TNF or IL-6.
      Finally, imiquimod stimulated TNF, IFN, and IL-6 production in cultures of mouse
      spleen and bone marrow cells. These studies demonstrate that imiquimod induces
      not only IFN but other cytokines as well, all of which may contribute to its
      biological activity.

PMID- 7507972
TI  - The role of tyrosine kinases and phosphotyrosine-containing recognition motifs in
      regulation of the T cell-antigen receptor-mediated signal transduction pathway.
AB  - T cell-mediated immune responses are initiated by interaction of antigen bound to
      a glycoprotein encoded by the major histocompatibility complex with the T cell
      antigen receptor (TCR). These recognition and binding steps are followed by
      multiple intracellular biochemical events. The earliest event detected is an
      increase in intracellular protein tyrosine phosphorylation that involves a
      complex interaction of tyrosine kinases and phosphatases. Subsequently, one
      observes an increase in protein serine/threonine phosphorylation, phospholipid
      hydrolysis, and changes in intracellular Ca2+ levels. These and other biochemical
      changes lead to cell proliferation, differentiation, and acquisition of effector
      functions. While binding of extracellular growth factors to receptors containing
      cytoplasmic protein tyrosine kinase (PTK) domains induces direct activation of
      their kinase activity, the multichain TCR lacks an intrinsic kinase domain and
      therefore represents a distinct type of receptor. It transduces signals via the
      interaction with, and activation of, non-receptor PTKs. Recent efforts directed
      at defining the TCR-linked signaling pathways have provided insight into the
      regulatory role of three PTKs, and the functional importance of some unique
      protein motifs in both TCR subunits and PTKs, which mediate critical protein
      protein interactions in this pathway.

PMID- 7507973
TI  - The interleukin-4 receptor: signal transduction by a hematopoietin receptor.
AB  - Over the last several years, the receptors for numerous cytokines have been
      molecularly characterized. Analysis of their amino acid sequences shows that some
      of these receptors bear certain motifs in their extracellular domains that define
      a family of receptors called the Hematopoietin receptor superfamily. Significant
      advances in characterizing the structure, function, and mechanisms of signal
      transduction have been made for several members of this family. The purpose of
      this review is to discuss the recent advances made for one of the family members,
      the interleukin (IL) 4 receptor. Other receptor systems have recently been
      reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140
      kDa IL-4-binding chain with the potential for associating with other chains. The
      IL-4 receptor transduces its signal by activating a tyrosine kinase that
      phosphorylates cellular substrates, including the receptor itself, and the 170
      kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the
      enzyme PI-3'-kinase and increases its enzymatic activity. These early events in
      the IL-4 receptor initiated signaling pathway may trigger a series of signals
      that will ultimately lead to an IL-4 specific biologic outcome.

PMID- 7507974
TI  - Standing calcium gradients in olfactory receptor neurons can be abolished by
      amiloride or ruthenium red.
AB  - Digital imaging and the patch clamp technique were used to investigate the
      intracellular calcium concentration in olfactory receptor neurons using the Ca2+
      indicator dyes fura-2 and fura-2/AM. The spatial distribution of Cai2+ as well as
      its modification by the drugs Amiloride and Ruthenium Red were studied. Resting
      calcium concentrations in cells loaded with fura-2/AM were between 10 and 200 nM.
      In cells that were loaded with the pentapotassium salt of fura-2 through the
      patch pipette, calcium concentrations were in the same range if ATP was added to
      the pipette solution. Otherwise, Ca2+ reached concentrations of approximately 500
      nM. Most of the observed cells showed a standing gradient of calcium, the calcium
      concentrations in the distal dendritic end of the cell being higher than in the
      soma. In some cells, the gradient was markedly reduced or abolished by adding
      either Amiloride or Ruthenium Red to the bath solution. In a few cells, neither
      drug had any effect upon the gradient. It is suggested that the inhomogenous
      spatial distribution of intracellular calcium in olfactory cells of Xenopus
      laevis is brought about by an influx of calcium ions through two different
      calcium permeable conductances in the peripheral compartments of the cells. The
      fact that only either Ruthenium Red or Amiloride abolished the standing calcium
      gradient further suggested that the two conductances blocked were presumably not
      coexpressed in the same cells.

PMID- 7507975
TI  - Axoplasmic organelles at nodes of Ranvier. I. Occurrence and distribution in
      large myelinated spinal root axons of the adult cat.
AB  - Using light microscopy (LM) and electron microscopy (EM) we have examined the
      occurrence and distribution of axoplasmic organelles in large myelinated nerve
      fibres of the L7 ventral and dorsal spinal roots of the cat with special
      reference to the paranode-node-paranode (pnp)-regions. Ninety-eight percent of
      the 550 Toluidine Blue-stained paranode-node-paranode-regions examined in the
      light microscope contained dark-blue bodies accumulated distal to the midlevel of
      the paranode-node-paranode-region. Further, a veil of Toluidine Blue positive
      material was observed in about 50% of the paranode-node paranode-regions. In
      about 25% of these paranode-node-paranode-regions the veil lay distal to the
      midlevel of the paranode-node-paranode-region and in the remainder it lay
      proximally. Electron microscopy suggested that the ultrastructural equivalents of
      the dark-blue bodies and of the veil were dense lamellar bodies and a diffuse
      granular material, respectively. Our calculations indicate that from 70% to more
      than 90% of some organelles (dense lamellar bodies, multivesicular bodies and
      vesiculo-tubular membranous organelles) present in an axon are accumulated in the
      paranode-node-paranode-regions. The occurrence of these organelles in the
      individual paranode-node-paranode-regions varied within wide limits also in
      adjacent fibres. The dense lamellar and multivesicular bodies dominated the
      distal part of the paranode-node-paranode-regions while the vesiculo-tubular
      membranous organelles dominated the proximal part, i.e. the organelles showed a
      mutual proximo-distal segregation with reference to the midlevel of the paranode
      node-paranode-region. Of seventeen paranode-node-paranode-regions analyzed
      ultrastructurally, seven were classified as 'fully segregated', that is 67% or
      more of the lamellar and multivescular bodies, present in the whole paranode-node
      paranode-region, lay distal to the mid-level, and 67% or more of the vesiculo
      tubular membranous organelles lay proximal to it.

PMID- 7507976
TI  - Axoplasmic organelles at nodes of Ranvier. II. Occurrence and distribution in
      large myelinated spinal cord axons of the adult cat.
AB  - The occurrence and distribution of axoplasmic organelles in large myelinated
      axons of the ventral, the lateral and the dorsal funiculi of L7 spinal cord
      segments of the cat have been studied using electron microscopy (EM). Most
      organelles were found to be concentrated to the paranode-node-paranode (pnp)
      regions and they showed their highest relative concentration in the constricted
      part of these regions, i.e. at the nodes of Ranvier. In the paranode-node
      paranode-regions of the lateral and dorsal funiculi, large dense bodies
      predominated distal to the nodal mid-level and vesiculo-tubular membranous
      organelles proximal to it. This pattern of organelle distribution, a proximo
      distal (with reference to the neuron soma) segregation of the organelles, was
      only faintly indicated in the paranode-node-paranode-regions of the alpha motor
      axons of the ventral funiculus. These paranode-node-paranode-regions were, apart
      from a weak proximo-distal segregation of a few organelles, characterized by
      deposits of electron dense granules and clusters of large round mitochondria. We
      conclude that there are two types of organelle accumulation and distribution in
      the paranode-node-paranode-regions of large spinal cord nerve fibres of the cat.
      One type is found in the lateral and dorsal funiculi, i.e. in axons with terminal
      (synaptic) fields inside the blood-brain-barrier. The other type is found in the
      alpha motor axons of the ventral funiculus, i.e. in axons with their terminal
      field in the PNS and thus outside the blood-brain barrier. It should be noted
      that retrogradely transported material in the alpha motor axons has passed
      through a long sequence of paranode-node-paranode-regions equipped with Schwann
      cells before it reaches the CNS, while material transported retrogradely in the
      axons of the dorsal and lateral funiculi has not. The following discussion
      includes a comparison of the organelle accumulation and distribution in these two
      types of CNS paranode-node-paranode-regions with the organelle accumulation and
      distribution observed in the paranode-node-paranode-regions of PNS axons.

PMID- 7507977
TI  - Differential expression of tenascin after denervation, damage or paralysis of
      mouse soleus muscle.
AB  - The expression of the extracellular matrix molecule tenascin was studied by
      immunocytochemistry and Western blotting in soleus muscles of adult mice after
      nerve damage (denervation), muscle injury (induced by enforced running or
      freezing) and functional block of synaptic transmission (botulinum toxin).
      Enhanced expression of tenascin in the extracellular spaces around focally
      damaged muscle fibres was found already 10 h after onset of running on a motor
      driven treadmill which causes muscle injury in soleus muscle. Tenascin expression
      reached a peak at 2-3 days post-exercise, after which it declined gradually and
      became undetectable by two weeks after injury. Similarly, cryo-damage of soleus
      muscles in situ led to upregulation of tenascin. Chronic muscle denervation after
      sciatic nerve transection caused a persistent (studied up to 31 days) expression
      of tenascin at denervated endplates and in intramuscular nerve branches but not
      in other tissue compartments. Local application of botulinum toxin Type A, which
      results in muscle inactivity but not in tissue degeneration, however, did not
      induce tenascin expression 12 h to 12 days post-injection. Expression of tenascin
      after denervation and muscle damage, but its absence after paralysis, were
      verified by SDS-PAGE and Western blot analysis. Independent of the type of injury
      (muscle, nerve or both) the known major isoforms of mouse tenascin, as judged by
      M(r) comparison, were re-expressed, with no preponderance of individual M(r)
      forms. These results show that tenascin expression in adult muscles is induced by
      both axon and muscle fibre damage but not by muscle inactivity. In contrast,
      NCAM, in accordance with previous observations, showed enhanced expression both
      as a result of inactivity and in association with tissue repair.

PMID- 7507978
TI  - Immunohistochemistry as a predictor of clinical outcome in patients given
      postoperative radiation for subtotally resected pituitary adenomas.
AB  - There is general agreement that postoperative radiation therapy is beneficial for
      patients with subtotally resected pituitary adenomas. We have identified 41 such
      patients treated during a 20-year period who received postoperative irradiation
      for a pituitary adenoma. The usual dose was 5040 cGy in 28 fractions. The mean
      follow-up time was 10.3 years. On routine hematoxylin and eosin (H&E) staining,
      there were thirty-three chromophobe, seven eosinophilic, and one basophilic
      adenoma. Tissue blocks were stained for growth hormone (GH), luteinizing hormone
      (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and/or
      adrenocorticotropin (ACTH) using the peroxidase-antiperoxidase
      immunohistochemistry (IHC) method. Routine H&E staining was a poor predictor of
      the IHC stain. While most patients with a known clinical endocrine syndrome
      stained positive on IHC for the suspected offending hormone, many patients
      without a clinical syndrome also stained positive indicating the presence of
      hormonally occult adenomas in this locally invasive group. The IHC stain results
      were compared to clinical outcome. The presence of positive GH IHC staining
      decreased the 15-year progression-free survival (PFS) from 100% to 64% compared
      to GH negative adenomas (p = 0.06). There was a trend toward decreased 15-year
      PFS in patients who did not stain for LH. Positive staining for prolactin, ACTH,
      or TSH had no influence on the progression-free survival. We conclude that
      additional prognostic information can be obtained in this subset of patients (by
      performing IHC analysis) that is not known by the clinical presentation or
      appearance on H&E stain.

PMID- 7507979
TI  - Glutamate-evoked release of arachidonic acid from mouse brain astrocytes.
AB  - Brain astrocytes in primary culture from the rat or the mouse have been shown to
      possess ionotropic and metabotropic glutamatergic receptors. The activation of
      both types of receptors is responsible for a rise in the cytosolic concentration
      of calcium, while the stimulation of metabotropic receptors induces the
      accumulation of inositol phosphates. In the present study, it is demonstrated
      that in striatal astrocytes from mouse embryos, glutamate evokes a release of
      arachidonic acid. The nonionotropic receptors involved in this effect appeared to
      be pharmacologically distinct from those coupled to phospholipase C: (1)
      glutamate displayed different dose-response curves for the production of inositol
      phosphates (biphasic: EC50 = 25 and 300 microM) and the release of arachidonic
      acid (monophasic: EC50 = 200 microM); (2) L(+)-2-amino-4-phosphonobutyric acid
      (AP4) only antagonized the glutamate-evoked release of arachidonic acid without
      altering the production of inositol phosphates; (3) when used at a concentration
      of 0.1 mM, quisqualate induced a higher formation of inositol phosphates than
      glutamate (2 mM) while, in contrast to glutamate, it only weakly stimulated
      arachidonic acid release when used either at 0.1 mM or 1 mM. L(+)-2-amino-3
      phosphonopropionic acid (AP3) suppressed both responses. The glutamate-evoked
      release of arachidonic acid seems to be oppositely regulated by protein kinases A
      and C. Indeed, the stimulation of adenylate cyclase by the beta-adrenergic
      agonist isoproterenol, vasoactive intestinal peptide, or pretreatment of striatal
      astrocytes with cholera toxin decreased the glutamate-evoked release of
      arachidonic acid. In contrast, ATP, which markedly stimulated inositol phosphate
      production, strongly potentiated the glutamate-evoked release of arachidonic
      acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507980
TI  - Long-term growth and remodeling of regenerated retino-collicular connections in
      adult hamsters.
AB  - The capacity of regenerating axons for long-term growth and synaptic plasticity
      was investigated in the visual system of adult hamsters. Four to six and 8-10
      months after the eye and the superior colliculus (SC) were linked by a peripheral
      nerve (PN) graft, the retinal ganglion cell (RGC) axons that had regrown into the
      SC were examined ultrastructurally. Together with the data from hamsters with
      similar PN grafts for 2 months (Carter et al., 1989), this study spans most of
      the life of these animals. The overall findings indicate that (1) the RGC axons
      extended twice as far into the SC and the number of RGC terminals increased 30
      fold between 2 and 4-6 months. These parameters did not change thereafter. The
      highest density of regenerated RGC terminals observed in the SC was 11.5% of
      controls. (2) The new RGC terminals acquired most of their normal ultrastructural
      characteristics by 2 months. (3) The mean size of the terminals was larger than
      in controls but decreased gradually, and there was a small increase in the size
      of the regenerated synapses. (4) At all times, the RGC terminals remained
      confined to the layers of the SC that normally receive retinal inputs, and their
      synapses were formed in normal proportions with the dendritic shafts and spines
      of SC neurons. Thus, there is a protracted long-term growth and remodeling of the
      RGC axons that have regenerated into the SC of these adult mammals.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7507982
TI  - Dynamic construction of a neural network from multiple pattern generators in the
      lobster stomatogastric nervous system.
AB  - In the stomatogastric nervous system (STNS) of the lobster Homarus gammarus, the
      rhythmic discharge of a pair of identified modulatory neurons (PS cells) is able
      to construct de novo a functional network from neurons otherwise belonging to
      other functional networks. The PS interneurons are electrically coupled and
      possess endogenous oscillatory properties that can be activated synaptically by
      stimulation of an identified sensory pathway. PS neurons themselves project
      synaptically onto the three major neural networks (esophageal, gastric mill, and
      pyloric) of the STNS. When a PS is rhythmically active in vitro, either
      spontaneously (rarely) or in response to direct stimulation, it dramatically
      restructures the otherwise independent activity patterns of all three target
      networks. This functional reconfiguration elicited by a single cell does not rely
      on changes in neuronal allegiance to pre-existing circuits, or on a simple merger
      of these different circuits. Rather, PS is responsible for the creation of an
      entirely new motor rhythm in that, via its widespread synaptic connections, the
      interneuron is able to subjugate the ongoing activity of the three STNS circuits
      and selectively appropriate individual elements to its own intrinsic rhythm. In
      addition, PS excites motor neurons that innervate dilator muscles of a valve
      situated between the esophagus and the stomach. The reorganization of the
      regional foregut motor rhythms by the interneuron is therefore coordinated to the
      opening of this valve, which itself carries sensory receptors that have been
      found to activate bursting in PS. Our data suggest that the role of PS in
      massively restructuring stomatogastric output is to generate a unique motor
      pattern appropriate for swallowing-like behavior. In a wider context, moreover,
      the results demonstrate that a neural network may not exist as a predefined
      entity within the CNS, but may be dynamically assembled according to changing
      behavioral circumstances.

PMID- 7507981
TI  - Input-output organization of the sensorimotor striatum in the squirrel monkey.
AB  - The basal ganglia receive massive inputs from the neocortex and send outputs that
      exert both inhibitory and disinhibitory control over parts of the frontal cortex
      and brainstem. Between these basal ganglia inputs and outputs lies the striatum,
      which receives most of the cortical afferents and projects to the basal ganglia
      output nuclei--the globus pallidus and substantia nigra. To analyze this system
      we conjointly labeled, in squirrel monkeys, sensorimotor cortical inputs to the
      striatum and striatal outputs to the globus pallidus. Anterograde tracers were
      injected into the motor (MI) and somatosensory (SI) cortical body maps, at sites
      determined by electrophysiological stimulation and recording. Retrograde tracers
      were stereotaxically injected into the external and internal pallidal segments
      (GPe and GPi). We found that multiple dispersed modules ("matrisomes") in the
      putamen that all received inputs from single body-part representations in
      sensorimotor cortex could, in turn, send convergent outputs to single sites in
      the pallidum. This divergence-reconvergence pattern was found for both GPe and
      GPi sites, and for inputs from both SI and MI cortex. Thus, information from a
      single functional region in the cortex can be split up at the striatal stage only
      to be brought back together in the pallidum. The temporary divergence may
      increase lateral interactions between sensorimotor matrisomes, as well as between
      matrisomes and striosomes. One function of striatal modularity may thus be to set
      up an associative network in the striatum, which might contribute to sensorimotor
      learning. We also found that some sets of matrisomes did not receive strong
      sensorimotor inputs, even though they projected to regions of GPe and GPi that
      are near the sensorimotor-recipient zones described above. Thus, the matrisomal
      system may sort MI/SI inputs and other inputs before transfer to paired regions
      of GPe and GPi.

PMID- 7507983
TI  - Primary afferent plasticity following partial denervation of the trigeminal
      brainstem nuclear complex in the postnatal rat.
AB  - Although interaxonal competition is believed to be an essential component of the
      normal development of numerous mammalian neuronal populations, there is
      considerable debate regarding the role of competition in the development and
      maintenance of the somatic sensory system. The results of recent investigations
      suggest that trigeminal primary afferents may compete for target territory in the
      brainstem, but it is unclear whether these interactions continue after birth. The
      present study explored this important issue by examining the response of
      individual trigeminal primary afferent neurons to partial denervation of the
      trigeminal brainstem nuclear complex at early postnatal ages. We utilized
      intracellular recording and HRP injection techniques to label primary afferent
      central terminal arbors in rats that sustained electrocautery of mystacial
      vibrissae in rows A, C, and E on the day of birth. A total of 42 low-threshold
      trigeminal primary afferent neurons were labeled in subnucleus interpolaris.
      Twenty-eight of these afferents supplied undamaged B or D row vibrissae while 14
      supplied lesioned vibrissae. Qualitative and quantitative analyses revealed that
      the arbors associated with undamaged afferents were enlarged (mean arbor area of
      13512 +/- 790.67 microns 2 vs normal area of 6130 +/- 214 microns 2) and were
      oriented toward the adjacent (partially denervated) territory. There was no
      significant change in the size of the lesioned afferent arbor area. The perimeter
      of the lesioned afferent arbors was increased, however, suggesting that the arbor
      shape had changed. This was confirmed with a form factor calculation that
      indicated that the circularity of the arbors associated with lesioned vibrissae
      was significantly reduced. Thus, while the arbors of undamaged afferents were
      enlarged and oriented in the direction of the partially denervated territory, the
      lesioned afferent arbors were not enlarged but assumed a flattened/elongate
      morphology within their appropriate row. The lesion-induced increase in the size
      of the undamaged afferent arbors was not associated with an increase in the
      number of bouton-like fiber swellings. The density of boutons was only 25% the
      value seen in normal animals. Thus, while the area supplied by the undamaged
      afferent arbors increased, there was no evidence that the absolute amount of
      terminal arbor was similarly increased (as would be the case if sprouting had
      occurred; see Renehan et al., 1989). We would therefore conclude that the
      undamaged afferents had undergone arbor expansion, but not sprouting. These data
      are consistent with prior suggestions that trigeminal primary afferents utilize
      some form of competitive interaction(s) to establish their final form and
      disposition. This competition would appear to continue into early postnatal
      periods.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7507984
TI  - ATP-activated current and its interaction with acetylcholine-activated current in
      rat sympathetic neurons.
AB  - Ionic current activated by extracellular ATP was characterized using whole-cell
      voltage clamp of rat sympathetic neurons isolated from superior cervical ganglia.
      ATP (10-1000 microM) activated an inward current (IATP) at negative holding
      potentials in almost all the cells (> 97%). The current was reversed near 0 mV in
      a quasi-physiological external solution, and the concentration dependence could
      be fitted by a curve with an EC50 value of 60 microM and a Hill coefficient of
      1.8. The relationship between IATP and the current activated by ACh (IACh) was
      examined. ACh (100 microM) activated an inward current one- to fivefold larger
      than the current activated by 100 microM ATP. IATP and IACh were not additive;
      the current activated by simultaneous application of ATP and ACh was only as
      large as the current activated by ACh alone. During current activation by ATP or
      ACh, the current activated by the other agonist became smaller, suggesting that
      these agonists reciprocally inhibit their excitatory responses. The reciprocal
      inhibition appeared to depend on the extent of channel opening because the
      reduction of the current elicited by each agonist was relieved when the current
      elicited by the other agonist had been desensitized. Suramin (100 microM), a
      purinoceptor antagonist, selectively inhibited IATP whereas two open-channel
      blockers of nicotinic receptor channels, hexamethonium (10-100 microM) and d
      tubocurarine (1-10 microM), inhibited IACh without affecting IATP. When 140 mM
      glucosamine was used as an external cation, only ATP but not ACh activated a
      considerable inward current at -150 mV. The ATP-induced glucosamine influx was
      reduced by simultaneous application of ACh. These results suggest that channel
      activation by ATP and that by ACh are not independent, and these two excitatory
      neurotransmitters negatively interact with each other at postsynaptic level in
      rat sympathetic neurons. The interaction between the ATP- and the ACh-induced
      conductances was hypothetically explained based upon our previous proposal of
      "channel overlap"; that is, ATP activates a subpopulation of the nicotinic
      receptor channels.

PMID- 7507985
TI  - Characterization of antibodies to the rat substance P (NK-1) receptor and to a
      chimeric substance P receptor expressed in mammalian cells.
AB  - Antibodies to neuropeptide receptors can be used to localize and characterize the
      receptors in tissues and cell lines. Two strategies were used to study the rat
      substance P receptor (SPR, NK-1) by immunological methods. First, a polyclonal
      antiserum was raised by immunizing rabbits with a peptide corresponding to the 15
      amino acid residues (KTMTESSSFYSNMLA, SPR393-407) at the intracellular C-terminus
      of the rat SPR coupled to bovine thyroglobulin. An antiserum was obtained with a
      titer for half-maximal binding of 125I-SPR393-407 of 1:70,000. Nonradioactive
      SPR393-407 inhibited 50% of binding at a concentration of 10 pM. Binding of 125I
      SPR393-407 to the antiserum was also displaced in a parallel manner by membrane
      proteins from tissues expressing high levels of the SPR (brain and submaxillary
      gland). Second, a chimeric SPR construct of a hydrophilic Flag peptide (DYKDDDDK)
      genetically engineered in sequence with the extracellular N-terminus of rat SPR
      was generated by polymerase chain reaction. The Flag-SPR chimera was expressed in
      rat kidney epithelial cells (KNRK) and judged to be fully functional, assessed by
      binding of 125I-substance P (apparent Kd of 5.63 nM) and calcium mobilization in
      response to substance P (EC50 of 0.66 nM). Antibodies to SPR393-407 and the Flag
      peptide stained the plasma membrane of KNRK cells expressing the native SPR or
      the Flag-SPR chimera. Staining was abolished by preincubation with SPR393-407 or
      the Flag peptide. Cells transfected with vector alone were unstained. The SPR
      antiserum recognized a broad protein band on Western blots of membranes prepared
      from cells expressing SPR but not from cells transfected with vector alone. The
      signal was quenched by preincubation of the antiserum with SPR393-407. By
      immunohistochemistry, the SPR antiserum was found to bind to neurons in the
      dorsal horn of the rat spinal cord and to ganglion cells in the myenteric plexus
      of the rat ileum near substance P-immunoreactive nerve fibers. Staining was
      abolished by preabsorption of the antiserum with SPR393-407. These antibodies can
      be used to localize the SPR in tissues and cells and to examine the function of
      the receptor in cell lines.

PMID- 7507986
TI  - The CSF myelin basic protein: a reliable marker of actual cerebral damage in
      hydrocephalus.
AB  - Raised ventricular CSF myelin basic protein (MBP) concentration has been
      evidenced in 17 shunted hydrocephalic patients. Contemporary evaluation both from
      ventricular and lumbar CSF samples showed a concentration ratio of 20:1. In all
      cases the raised values of ventricular CSF concentration of MBP demonstrated a
      significant decrease after shunt operation. This preliminary report suggests that
      this marker is an important index of actual brain damage in hydrocephalus and
      could be taken in account for the indication of shunt operation.

PMID- 7507987
TI  - Cellular bound beta-carotene quenches singlet oxygen in man.
AB  - It is often postulated that a major role of carotenoids in biology and medicine
      involves their ability to quench a toxic form of oxygen, known as singlet oxygen,
      although direct observations of such mechanisms do not exist. Using beta
      carotene, bound to lymphocytes taken from human blood, we have used a direct,
      pulsed laser, physical chemical technique and, separately, a biological method to
      show a particularly efficient quenching reaction of singlet oxygen by carotene in
      a cellular environment.

PMID- 7507988
TI  - Identifying children who need early intervention services.

PMID- 7507989
TI  - Management of malignant ascites with a vascular port.
AB  - A 15 year old with severe malignant ascites, refractory to medical management,
      was treated with a venous port. This proved to be an effective way to control the
      ascites and was easily placed under local anesthesia, with little risk or
      discomfort to the patient.

PMID- 7507990
TI  - Severe constipation with diffuse intestinal myenteric hyperganglionosis.
AB  - The authors report a case of neuronal intestinal dysplasia in a 6-year-old girl.
      The disease is characterized by hyperplastic ganglia throughout the large and
      small intestine, associated with severe constipation. To better understand the
      pathophysiology of this disease the authors investigated the histopathologic,
      ultrastructural, and immunohistochemical characteristics of the intestinal tissue
      in this case. The hyperganglionosis was associated with immunohistochemical
      findings of intact expression of the neuropeptides controlling the peristaltic
      reflex, through lower expression of calcitonin-gene related peptide. With the
      recent progress in our understanding of the neural regulation of gastrointestinal
      function, it may now be possible to begin to understand the complex
      pathophysiological mechanisms underlying gastrointestinal motility disorders.

PMID- 7507991
TI  - Neutralization epitopes on HIV pseudotyped with HTLV-I: conservation of
      carbohydrate epitopes.
AB  - One mechanism for expanding the cellular tropism of human immunodeficiency virus
      (HIV) in vitro is through formation of phenotypically mixed particles
      (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we
      found that pseudotypes allow penetration of HIV particles into CD4-negative
      cells, previously nonsusceptible to HIV infection. The infection of CD4-negative
      cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be
      significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120
      monoclonal antibody. This may represent a possibility for pseudotypes to escape
      neutralization by the immune system in vivo. Previous reports have suggested that
      carbohydrate structures may be conserved neutralization epitopes on retroviruses.
      In this study, the neutralizing capacity of lectins and anti-carbohydrate
      monoclonal antibodies was found to block infection by cell-free pseudotypes in
      CD4-negative cells. We suggest that although viral cofactors might expand the
      tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate
      neutralization epitopes.

PMID- 7507993
TI  - Pharmacological evidence that flow- and potassium-induced contraction of rabbit
      facial vein may involve the same calcium entry pathway.
AB  - Flow-induced contraction depends upon extracellular Ca++, but the underlying Ca++
      entry pathway involved is unknown. We chose the rabbit facial vein to carry out
      this study because, in addition to contracting to a number of pharmacological
      agents and developing myogenic tone in response to stretch in vitro, flow-induced
      contraction also can be consistently demonstrated. Our goal was to determined
      whether the Ca++ entry pathway for flow-induced contraction could be
      distinguished from that involved in K(+)-, histamine- and stretch-induced
      contraction through the use of a Ca++ entry activator: Bay K 8644 and the Ca++
      entry blockers nifedipine, diltiazem and verapamil and also cobalt and manganese.
      All four types of contractions studied are dependent on extracellular Ca++ Flow-
      and K(+)-induced contraction were equally sensitive to inhibition by nifedipine,
      verapamil and diltiazem. Those to histamine and stretch were not. Furthermore,
      the flow- and K(+)-induced contractions were enhanced equivalently by the calcium
      channel activator, Bay K 8644, but to a lesser degree than those to histamine and
      stretch. The inorganic calcium channel blockers, Co++ and Mn++ effected equally
      flow-, K(+)- and histamine-induced contraction. They were more potent in their
      inhibition of stretch-induced contraction. Our results suggest that flow- and
      K(+)-induced contractions depend on a similar Ca++ entry system into vascular
      smooth muscle: probably a voltage-gated Ca++ entry pathway, which is different
      from that utilized by histamine and stretch.

PMID- 7507992
TI  - Potassium channel inhibitors attenuate neuromodulatory effects of atrial
      natriuretic factor in the rabbit isolated vas deferens.
AB  - This study tested the hypothesis that neuromodulatory effects of atrial
      natriuretic factor (ANF) are mediated by an activation of potassium channels in
      the rabbit isolated vas deferens. The neuromodulatory effects of ANF were tested
      in the presence of the potassium channel inhibitors, tetraethylammonium, 4
      aminopyridine, glibenclamide and charybdotoxin. The effects of the first three
      were ascertained by their prevention of neuromodulatory effects of a cromokalim
      enantiomer (BRL 38227), which opens ATP-sensitive potassium channels. The
      nonspecific potassium channel inhibitors, tetraethylammonium (2 mM) and 4
      aminopyridine (2 mM) blocked inhibitory effects of both ANF and BRL 38227 on the
      electrically-induced adrenergic contraction in the rabbit vas deferens.
      Glibenclamide (10 microM), an inhibitor of ATP-sensitive potassium channels,
      failed to antagonize ANF effects, but blocked the actions of BRL 38227.
      Charybdotoxin (100 nM) is known to block large conductance calcium-activated
      potassium channels, and it attenuated the neuromodulatory effects of ANF;
      however, the effects of BRL 38227 were sustained in the presence of
      charybdotoxin. These results are consistent with the hypothesis that the
      neuromodulatory action of ANF is mediated by the activation of potassium
      conductances. The potassium channel involved is not an ATP-sensitive channel,
      because glibenclamide failed to alter the neuromodulatory activity of ANF. We
      hypothesize that ANF effects could be mediated by an activation of either calcium
      activated or outward rectifying potassium channels.

PMID- 7507994
TI  - Quantitative and temporal analysis of the cellular interaction of FK-506 and
      rapamycin in T-lymphocytes.
AB  - The structurally related immunosuppressive macrolides FK-506 and rapamycin (RAP)
      exert distinct biological effects: inhibition of interleukin-2 production and
      inhibition of interleukin-2-induced proliferation, respectively, through binding
      to intracellular receptors, termed FKBPs. Although the interaction of these drugs
      with purified FKBPs in vitro has been well characterized, little is known about
      their interaction with FKBPs in living cells. Here, we used [3H]-dihydro-FK-506
      as a probe to examine the binding of these macrolides in both normal mouse
      splenic T-cells and the human Jurkat T-cell lymphoma. These cells were found to
      accumulate the radioligand, predominantly in the cytosol, to a saturable level
      corresponding to an estimated concentration of 6 to 7 microM. Half-maximal
      suppression of T-cell activation was shown to require radioligand occupancy of
      only 3 to 5% of the pool of available intracellular binding sites (FKBPs).
      Moreover, the binding and immunosuppressive effect of the radioligand could not
      be removed by extensive washing and remained stable for at least 6 hr upon
      incubation of the cells at 37 degrees C. However, a molar excess of either FK-506
      or RAP was found to rapidly displace [3H]-dihydro-FK-506 from its cellular
      binding sites. Consistently, FK-506 and RAP were able to antagonize mutually
      their immunosuppressive activities even when added several hr after each other to
      T-cell cultures. We took advantage of the reciprocal antagonism of FK-506 and RAP
      to define their apparent affinities for the functionally relevant cellular
      receptors by Schild analysis. This indicated that the drugs compete for a single
      cellular receptor with similar KdS and, therefore, may mediate their
      immunosuppressive action upon interaction with similar or highly related FKBPs.

PMID- 7507995
TI  - Role of the NH2-terminus of substance P in the inhibition by capsaicin of
      behavioral sensitization to kainic acid-induced activity in the adult mouse.
AB  - Activation of primary afferent C-fibers by repeated intrathecal injection of
      kainic acid (KA) in mice is inhibited after pretreatment with capsaicin. The
      increased behavioral response to multiple injections of KA is thought to be
      brought about by an action of the NH2-terminus of substance P (SP). In light of
      our recent observation that the antinociceptive effect of capsaicin may also
      involve an action of the NH2-terminus of SP, we tested the hypothesis that
      capsaicin inhibits behavioral sensitization to KA by a desensitization to the
      action of the NH2-terminus of SP. Using adult mice, pretreatment (24 hr) with
      either capsaicin (0.8 micrograms) or SP(1-7) (1 and 10 nmol) attenuated
      sensitization of the behavioral response to four injections of 25 pmol of KA at 2
      min intervals. Pretreatment with 10 nmol of the COOH-terminal SP fragment, SP(5
      11), had no effect. [D-Pro2,D-Phe7]-SP(1-7), a SP NH2-terminal antagonist,
      injected 5 min before capsaicin or SP(1-7), inhibited the effects of both
      capsaicin and SP(1-7) on KA sensitization whereas the COOH-terminal neurokinin
      antagonist, [D-Pro2,D-Trp7,9]-SP, did not. The similarities in behavioral
      responses after treatment with SP(1-7) or capsaicin, together with the
      sensitivity of these effects to D-SP(1-7), suggest that SP released in response
      to capsaicin may inhibit subsequent KA-induced activity 24 hr later. This action
      of SP appears to be brought about by its NH2-terminus and/or an accumulation of
      its NH2-terminal metabolites after capsaicin treatment.

PMID- 7507996
TI  - Modulation of nonadrenergic noncholinergic neural bronchoconstriction by
      bradykinin in anesthetized guinea pigs in vivo.
AB  - The modulatory effect of bradykinin on excitatory nonadrenergic noncholinergic (e
      NANC) neural constrictor responses was examined in anesthetized guinea pig
      airways in vivo. e-NANC responses were obtained by bilateral vagal stimulation in
      the presence of atropine (1 mg/kg i.v.) and propranolol (1 mg/kg i.v.).
      Indomethacin (5 mg/kg i.v.) and captopril (1 mg/kg i.v.) were pretreated to avoid
      the indirect effects of bradykinin by producing prostaglandins and to prevent
      endogenous breakdown of bradykinin, respectively. Bradykinin (0.01-1 nmol/kg
      i.v.) potentiated e-NANC responses in a dose-dependent manner. The potentiation
      was significant with 0.1 and 1 nmol/kg of bradykinin, 22.7 +/- 3.2% (mean +/-
      S.E.; P < .01) and 34.5 +/- 4.7% (P < .01), respectively), compared with that in
      sham-injected control animals (-4.7 +/- 3.6%). The potentiation of e-NANC
      responses by bradykinin (1 nmol/kg i.v.) was abolished by the subsequent
      administration of a bradykinin B2 receptor antagonist, HOE140 (0.1 mumol/kg
      i.v.), that was without effect on e-NANC responses by itself. The contraction
      induced by exogenous administration of substance P (1 nmol/kg i.v.) was not
      affected by the same dose of i.v. bradykinin; the change in substance P-induced
      bronchoconstriction was 9.2 +/- 8.3% with and 3.2 +/- 3.6% without bradykinin (P
      > .05). These results suggest that bradykinin potentiates e-NANC responses in
      guinea pig airways in vivo via B2 receptors which are possibly on prejunctional
      sites.

PMID- 7507998
TI  - Pharmacological characterization of presynaptic calcitonin gene-related peptide
      (CGRP) receptors on CGRP-containing vasodilator nerves in rat mesenteric
      resistance vessels.
AB  - Rat mesenteric arteries are innervated by calcitonin gene-related peptide (CGRP)
      containing vasodilator nerves (CGRP nerves). This study investigated the presence
      of presynaptic CGRP receptors on CGRP nerves and the receptors' role in the
      regulation of CGRP release from these nerves. The rat mesenteric vascular bed was
      perfused with Krebs' solution containing 7 microM methoxamine plus 5 microM
      guanethidine to produce active tone and block adrenergic neurotransmission. In
      this preparation, periarterial nerve stimulation (PNS;2 Hz) and bolus infusion of
      CGRP (50 pmol) caused a decrease in perfusion pressure caused by vasodilation.
      Vasodilator response to PNS was abolished by 0.3 microM tetrodotoxin and by 1
      microM human CGRP[8-37] (CGRP[8-37]), a CGRP receptor antagonist, which also
      abolished the response to bolus infusion of CGRP. Perfusion of CGRP (0.03-0.5 nM)
      dose-dependently inhibited vasodilator response to PNS, whereas it did not affect
      the response to bolus infusion of CGRP. The inhibitory effect of CGRP (0.3 nM)
      was antagonized by CGRP[8-37] (3 and 10 nM). Lower concentrations of CGRP[8-37]
      (1-10 nM) potentiated the vasodilator response to PNS, but higher concentrations
      (100 nM-1 microM) inhibited the response. The vasodilator response to bolus
      infusion of CGRP was dose-dependently inhibited by CGRP[8-37]. Eel calcitonin (5
      and 50 microM), forskolin (0.01 and 0.1 microM), 3-isobutyl-1-methylxanthine (0.3
      and 1 microM) and cyclic 8-bromo-adenosine 3':5'-monophosphate (10 and 100
      microM) had no effect on the PNS-induced vasodilation. These results suggest that
      CGRP nerves are endowed with presynaptic CGRP receptors, which regulate CGRP
      release from the nerves via a negative feedback mechanism.

PMID- 7507997
TI  - Dynamics of the actions of tetrahydro-9-aminoacridine and 9-aminoacridine on
      glutamatergic currents: concentration-jump studies in cultured rat hippocampal
      neurons.
AB  - The actions of 1,2,3,4-tetrahydro-9-aminoacridine (THA) and 9-aminoacridine (9
      AA) on glutamatergic receptors were studied using the whole-cell and outside-out
      variants of the patch-clamp technique. Typically, either N-methyl-D-aspartate
      (NMDA) or kainate alone or combined with various concentrations of THA or 9-AA
      was applied via a U tube to activate whole-cell currents. Other superfusion
      techniques were also used. THA (25-50 microM) and 9-AA (10-25 microM) reduced the
      peak and steady-state amplitudes of NMDA-activated whole-cell inward currents and
      had no significant effect on outward currents. At higher concentrations, these
      agents produced a delayed current peak in addition to a further depression of the
      current size. A delayed current peak was a high-amplitude current peak delayed in
      relation to the time course of control currents. THA and 9-AA were much less
      potent in blocking kainate-activated currents. Also, the blockade of kainate
      currents was voltage independent, and no delayed current peak was generated. With
      the same superfusion method, the antagonists APV (DL-2-amino-5-phosphonovaleric
      acid) and Mg++ were tested independently of THA or 9-AA and were found not to
      produce delayed current peaks or NMDA-activated whole-cell currents. Bath
      perfusion of THA (250 microM) abolished the delayed current peaks produced by
      pulse application of NMDA and THA, whereas bath perfusion of the competitive
      blocker APV did not have this effect. High concentrations of glycine (10 microM)
      did not alter THA's blocking effects or the production of delayed current
      peaks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7507999
TI  - Interstitial collagen is increased in the non-infarcted human myocardium after
      myocardial infarction.
AB  - In this study we report the changes of interstitial collagen in the human non
      infarcted interventricular septum after a myocardial infarction as well as in
      hypertrophic human hearts with or without hypertension. The collagen amount was
      determined with the Sirius Red morphometry technique, which enabled us to perform
      these studies on routinely processed, paraffin embedded sections. The collagen
      amount was significantly increased in the septum of infarct patients as compared
      to non-infarcted controls (P < 0.001). The collagen amount in the septum of the
      hypertensive hypertrophy group (HH) was significantly increased as compared to
      the non-hypertensive hypertrophy group (NHH) (P < 0.01). The collagen content in
      the NHH was not significantly different from the controls in the infarct group,
      while the collagen amount in the HH showed no significant difference to the
      collagen content in the infarct group. The results indicate that collagen
      deposition is increased in the non-infarcted myocardium after a myocardial
      infarction, as well as in the hypertensive hypertrophied myocardium. The data
      suggest that the appearance of excessive collagen is not mediated by cardiac
      hypertrophy per se, but that the underlying cause, infarction or hypertension, is
      the significant factor.

PMID- 7508000
TI  - Inhibition of neointimal hyperplasia by blocking alpha V beta 3 integrin with a
      small peptide antagonist GpenGRGDSPCA.
AB  - PURPOSE: Neointimal hyperplasia is a leading cause of restenosis after vascular
      procedures. Recent findings showed that smooth muscle cell (SMC) migration from
      the media into the neointima is a critical step in the development of the
      hemodynamically compromising neointimal lesion. Moreover, integrins are believed
      to play a role in SMC motility. Therefore we studied the role of one ubiquitous
      integrin, alpha V beta 3, in SMC migration. METHODS: Transwell assay was used to
      study in vitro migration of human and rabbit SMCs after stimulation with platelet
      derived growth factor (PDGF). A neutralizing monoclonal antibody to alpha V beta
      3, LM609, and a specific arginine-glycine-aspartic acid (RGD) antagonist,
      GpenGRGDSPCA, were used in the migration assay to inhibit alpha V beta 3-mediated
      SMC migration. In addition, GpenGRGDSPCA was administered locally to rabbit
      carotid artery after balloon angioplasty to determine the effect of blocking
      alpha V beta 3 on neointimal hyperplasia. RESULTS: We showed that PDGF-induced
      human SMC migration is mediated by the alpha V beta 3 integrin by use of LM609 to
      inhibit migration and that SMC migration is RGD dependent by use of GpenGRGDSPCA
      to inhibit migration. We have also inhibited rabbit SMC migration with
      GpenGRGDSPCA to demonstrate the cross-species preservation of the RGD peptide
      sequence in SMC mortality. Finally, when we administered GpenGRGDSPCA locally to
      rabbit carotid artery after balloon angioplasty, there was a statistically
      significant reduction in neointimal lesion formation compared with arteries
      administered an inactive peptide or saline solution. CONCLUSIONS: We have
      demonstrated the important role of the alpha V beta 3 integrin in SMC migration
      in vitro and in neointimal hyperplasia in vivo.

PMID- 7508001
TI  - Balloon pulmonary valvuloplasty for infants with severe tetralogy of Fallot.
AB  - Balloon pulmonary valvuloplasty was performed in 3 infants with severe tetralogy
      of Fallot at days 24, 54 and 86 because of progressive hypoxemia. In two
      patients, the balloon catheter (4 cm long, 5-8 mm diameter) could not pass
      through the pulmonary valve. This necessitated a smaller balloon and required a
      two-step procedure. Initially, a coronary artery balloon (2 cm long, 3.5 mm
      diameter) was used. Following balloon valvuloplasty, arterial oxygen saturation
      increased from 63 to 83% in case 1, from 69 to 85% in case 2 and 63 to 86% in
      case 3. Immediate postvalvuloplasty right ventricular cineangiography revealed
      that the maximal opening diameter of the pulmonary valve leaflets increased from
      1-2 mm to 3-4 mm in cases 1 and 3, and from 2-3 mm to 4-5 mm in case 2. No
      significant complications occurred. Echocardiographic follow-up data showed that
      the diameter of the right ventricular outflow tract and pulmonary arteries
      increased with age. The present results show that the pulmonary valvuloplasty is
      an effective procedure for relief of pulmonary valve stenosis in tetralogy of
      Fallot and to improve oxygenation and growth of the pulmonary arteries and right
      ventricular outflow tract without the need of an immediate aortopulmonary shunt.

PMID- 7508002
TI  - [Effect of combination chemotherapy for elderly patients with malignant
      lymphoma].
AB  - The remedial effect in elderly patients with malignant lymphoma in two groups
      treated with combination chemotherapy, one including doxorubicin (ADM) (A group)
      and the other excluding ADM (V group) were compared. Forty patients aged 65 years
      or more with malignant lymphoma were entered from January 1982 to December 1991.
      The A group was made up of 10 patients and the V group of 18 patients. As to
      pathological classification, two of the A group had low grade malignancy
      lymphoma, four had intermediate grade and three had high grade. Four of the V
      group had low grade, eight had intermediate grade and five had high grade. In
      terms of clinical stage, three of the A group were in stage II, 3 in stage III
      and 4 in stage IV. Two of the V group were in stage II, 7 in stage III and 9 in
      stage IV. The effective rate for the A group was 90% and the V group was 61%. The
      survival rate over five years in the A group was 37.5% and 21.8% in the V group.
      There were no adverse effects on the cardiovascular system in the A group. No
      significant differences of effects were shown in this study, however, the A group
      showed a higher tendency in terms of the CR rate and the survival rate. Cases of
      early death during chemotherapy were few and the quality of life of the patients
      was raised by discharge in the A group. Combination chemotherapy including ADM
      appears to be satisfactory in aged patients with malignant lymphoma.

PMID- 7508003
TI  - [Effect of G-CSF and M-CSF on busulfan-induced marrow failure in a 91-year old
      patient with essential thrombocythemia].
AB  - A 91-year-old patient with essential thrombocythemia presented with marked bone
      marrow suppression induced by long-term administration of busulfan. Her
      pancytopenia extended for over two months even after the cessation of busulfan,
      suggesting that she had developed a severe decrease in hematopoietic reserve. We
      administered G-CSF and M-CSF to accelerate recovery from marrow failure and to
      evaluate the recovery of hematopoiesis. The standard doses of G-CSF and M-CSF
      increased her neutrophil and platelet counts sufficiently but only transiently.
      Transient eosinophilia was also noted after cessation of M-CSF. The possibility
      that the expansion of abnormal clone(s) induced the transient increase in
      platelet and eosinophil counts could not be completely excluded. We suggest that
      the administration of hematopoietic growth factors should be limited to patients,
      irrespective of age, who present marked clinical symptoms attributable to marrow
      failure when the patient has a chronic myeloproliferative disorder.

PMID- 7508004
TI  - Expression of glycolipid blood group antigens in single human kidneys: change in
      antigen expression of rejected ABO incompatible kidney grafts.
AB  - Total neutral glycolipid fractions were separated into molecular species on thin
      layer chromatography plates and detected by immunostaining with monoclonal anti
      blood group antibodies. Blood group A antigens based on type 1, 2, 3 and 4
      carbohydrate core saccharides were present in kidneys of A1 and A1B individuals.
      Blood group A2 individuals expressed only small amounts of A antigen compared to
      A1 individuals especially of the type 3 and 4 compounds. Kidneys from non
      secretor individuals contained less A antigen compared to secretor individuals,
      and in both groups a variation in the antigen expression between single
      individuals was noted. Blood group A type 2 and 3 (which is an extension of A
      type 2) antigens were present both as basic 6 and 9 sugar structures as well as
      extended saccharide chains migrating in the 8 to 11 sugar interval. In contrast,
      the type 1 chain based A and Lewis antigens were only present as their basic 5 to
      7 sugar chains, and no elongated structures were found. Four cases of A2 kidneys
      initially transplanted into O recipients and removed after 5, 12, 21 days and 4
      years, respectively, were also analyzed. Two of these kidneys, originating from
      the same donor, showed a difference in A antigen expression. The kidney
      functioning for four years (lost due to chronic rejection) completely lacked X
      antigen with five sugar residues (present in all other individuals) and contained
      a large amount of A antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508005
TI  - Incidence and risk factors for hepatitis C seroconversion in hemodialysis: a
      prospective study. The UCL Collaborative Group.
AB  - To delineate the incidence and risk factors for seroconversion (SC) for HCV, from
      May 1991 to November 1992 we followed all 401 patients (no i.v. drug abusers)
      dialyzed in 15 Belgian hemodialysis (HD) units, none of which isolates anti-HCV
      (+) patients. The sensitive ELISA II test was performed in the same laboratory
      for all patients. ELISA II (+) sera were considered truly positive if specific
      antibodies were detected by RIBA II against at least one HCV antigen. Blood
      transfusions given from 12 months prior to inclusion in the study, dialyzer reuse
      and frequency of dialysis monitor sterilization were recorded. In May 1991,
      prevalence of truly positive ELISA II tests averaged 13.5% (54/399). During the
      three consecutive six-month periods, ELISA II became truly positive in 3 of 305
      (1%), 4 of 314 (1.3%) and 1 of 313 (0.3%) patients, respectively, which was an
      average yearly incidence of 1.7%. SC was preceded (1 to 6 months) in all cases by
      an unexplained, unprecedented increase in the alanine aminotransferase level. The
      mean monthly rate of transfusions was significantly higher (P < 0.001) in eight
      patients with SC (0.7 +/- 0.6 U) than in 393 patients without SC (0.1 +/- 0.01
      U). However, three of eight patients with SC had not been transfused at all. SC
      was observed in only 3 of 13 units (1, 3 and 4 cases, respectively) dialyzing
      ELISA (+) patients. In the unit with three SC, patients were always assigned a
      fixed station: SC was observed only in patients dialyzed next to an ELISA II (+)
      patient (3 of 8 vs. 0 of 30, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508006
TI  - Expression of apolipoprotein B epitopes in low density lipoproteins of
      hemodialyzed patients.
AB  - Serum and isolated low-density lipoprotein (LDL) composition abnormalities were
      investigated in 20 hemodialyzed patients with chronic renal failure and 15
      healthy normolipidemic subjects for comparison. LDL apolipoprotein B (apo B)
      epitope accessibility was determined by the use of seven monoclonal antibodies
      (Mabs). These Mabs recognize fragments on the N-terminal part of apo B (Mabs B1,
      B4), on the middle part (Mab BL7), on the C-terminal (Mabs BA11, BL3), and the
      two remaining Mabs recognize conformational epitopes of apo B (BL5, DA7). Mab
      BA11 recognizes a fragment of apo B which interacts with the B/E receptor. In
      hemodialyzed patients, LDL content of triglycerides (P < 0.001) and apo CIII (P <
      0.005) was increased, while cholesteryl esters (P < 0.005) were decreased. The
      accessibility of BL5 epitopes of LDL apo B was enhanced (P < 0.05), while BA11
      epitope expression was decreased (P < 0.01). The conformation of patients' LDL
      (CRF-LDL) was probably abnormal and seemed to be related to some modification of
      the lipidic environment. It is important to consider a structural modification as
      it alters the B/E receptor recognition domain of apo B. These results confirm LDL
      abnormalities in hemodialyzed patients and suggest a possible modification of the
      recognition of the LDL by cells.

PMID- 7508007
TI  - Molecular phenotype of simian virus 40 large T antigen-induced primitive
      neuroectodermal tumors in four different lines of transgenic mice.
AB  - BACKGROUND: We compared the molecular phenotypes of central nervous system tumors
      arising in four different lines of transgenic mice (TGM) carrying the Simian
      virus 40 large T antigen driven by different promoters or enhancers. Two of the
      four lines developed primitive neuroectodermal tumors (PNETs) in the brain stem
      or pineal gland. A third TGM line developed retinoblastomas (a PNET-like tumor of
      the retina) as well as PNETs in the mesencephalon, while the fourth TGM developed
      retinoblastomas and adrenal pheochromocytomas. EXPERIMENTAL DESIGN: The
      expression of developmentally regulated polypeptides specific for the neuronal or
      glial lineage was examined in these PNETs using immunohistochemistry and Western
      blotting. RESULTS: Neoplastic cells in all of the PNETs exhibited neuronal, but
      no glial specific markers as evidenced by the invariable expression of
      synaptophysin, but no detectable glial fibrillary acidic protein or myelin basic
      protein. PNETs with a more differentiated neuronal phenotype expressed multiple
      neuronal polypeptides. The phenotypic properties of these PNETs closely resembled
      those found in human brain PNET biopsy samples and cell lines derived therefrom.
      CONCLUSIONS: We conclude that Simian virus 40 T antigen-induced PNETs in TGM
      exhibit the molecular phenotype of developing neurons or neuronal progenitor
      cells. Although many factors could influence the phenotype of these experimental
      PNETs (e.g., promoter, site of integration of the transgene) these PNETs appear
      to be suitable TGM models of human PNETs of the central nervous system.

PMID- 7508008
TI  - Natriuretic Factors and Hypertension. Proceedings of a satellite symposium to the
      14th ISH meeting. Sevilla, Spain, June 19-20, 1992.

PMID- 7508009
TI  - Effects of sodium-transport inhibition in human resistance arteries.
AB  - It is hypothesized that endogenous inhibitors of active sodium transport may lead
      to an increase in peripheral vascular resistance. From studies in animal conduit
      arteries there is substantial evidence that cardiac glycosides may increase
      tension. A number of studies from our laboratory demonstrate that inhibition of
      active sodium transport may also increase tension in human resistance arteries,
      and that reduced Ca efflux via Na/Ca exchange could be a contributory mechanism.
      Further experiments also have suggested that endogenous inhibitors of sodium
      transport could lead to an increase in peripheral vascular resistance by reducing
      endothelium-dependent relaxation.

PMID- 7508011
TI  - Digitalis-like compounds in the toad Bufo viridis: interactions with plasma
      proteins.
AB  - Digitalis-like compounds (DLC), normal constituents of animal tissues, are
      possible regulators of the Na+,K(+)-ATPase implicated in water and salt
      homeostasis. DLC are present in toad (Bufo viridis) tissues. Although DLC highest
      levels were found in toad skin, it was also detected in plasma and many internal
      organs. The abundant distribution and the different levels of DLC in various
      tissues exclude the possibility that toxicity is the only function of these
      compounds in the toad. The concentration of DLC in toad plasma is 30 microM, out
      of which 25-30% is bound to plasma proteins. Fractionation of toad plasma
      proteins on a G-100 Sephadex column followed by the extraction of DLC from the
      plasma proteins revealed that DLC are bound primarily to proteins of 48,000
      53,000 Da. These results establish the existence of bufodienolide-binding
      protein(s) in animal plasma.

PMID- 7508010
TI  - Role of ouabain-like factors in hypertension: effects of ouabain and certain
      endogenous ouabain-like factors in hypertension.
AB  - Several reports suggest the presence of sodium-potassium pump inhibitor in plasma
      and various tissues, particularly during volume-expanded state and low-renin
      hypertension. It has been hypothesized that by inhibiting the cardiovascular
      muscle-cell Na(+)-K+ pump, this inhibitor can constrict blood vessels, enhance
      vasoconstriction, and increase cardiac contractility, thereby raising blood
      pressure. Only two such endogenous inhibitors have been chemically characterized:
      the bufodienolide derivative, resibufogenin, obtained from toad skin and plasma;
      and a factor with the same structure (based on mass spectral analysis) as
      ouabain, from human plasma. However, unlike bufalin (aglycone), which is almost
      structurally identical to resibufogenin, neither ouabain nor ouabagenin (aglycone
      of ouabain) caused a sustained increase in blood pressure when infused in
      equimolar doses during a 30-min period in rats. Because the rat is 10(4)-fold
      less sensitive to ouabain than the human is, we wondered whether the absence of a
      response to ouabain was due to the short infusion time. Therefore, in new
      experiments ouabain was administered chronically during a 6- to 7-week period to
      two-kidney normal rats and rats with 70, 60, and 25% reduced renal mass. Reduced
      renal mass rats were used because these rats have decreased sodium excretion
      capacity, and thus we hoped the action of exogenous ouabain would be potentiated
      in these volume-expanded rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508012
TI  - Cytochrome P450-dependent arachidonate metabolites affect renal transport in the
      rabbit.
AB  - Arachidonic acid (AA) inhibited 86Rb uptake in a dose-dependent manner in rabbit
      medullary tubules representing the thick ascending limb of the loop of Henle
      (mTALH). We have shown that CoCl2 treatment of rabbits reduced renal AA
      metabolism by cytochrome P450-dependent enzymes (P450). After CoCl2 treatment, AA
      was without effect on 86Rb uptake in mTALH cells. However, the two principal P450
      AA metabolites produced by the mTALH, 20-HETE and 20-COOH-AA, inhibited 86Rb
      uptake in a dose-dependent manner in mTALH cells whether obtained from control or
      CoCl2-treated rabbits. These data support our hypothesis that CoCl2 treatment
      impairs ion transport function of mTALH cells by blocking cytochrome P450-AA
      metabolism, a blockade circumvented by the relevant P450-AA metabolites.

PMID- 7508013
TI  - A possible connection between an increased concentration of a cytochemically
      detectable substance in the hypothalamus of the spontaneously hypertensive rat
      and certain cerebral cholinergic disturbances.
AB  - The hypothalamus of the spontaneously hypertensive rat (SHR) contains an
      increased concentration of a cytochemically detectable choline-like substance,
      the physicochemical properties of which are similar to the choline analogue
      dimethyl methylene immonium. In the hypothalamus of the adult SHR there is an
      increased turnover of acetylcholine in the cholinergic pressor posterior
      hypothalamic nucleus and the neurons of the dorsomedial cholinergic depressor
      nucleus are atrophic, possibly due to diminished cholinergic activity. Both of
      these changes are pressor. It is suggested that an increased hypothalamic content
      of a choline-like analogue might either be responsible for, or an indicator of,
      these abnormalities.

PMID- 7508015
TI  - Natriuretic properties of melanocyte-stimulating hormones.
AB  - Proopiomelanocortin (POMC) is a protein that contains the amino acid sequences of
      numerous peptide hormones, including the melanocyte-stimulating hormones (MSH).
      MSH peptides of alpha, beta, and gamma primary structure are present in plasma,
      and all exhibit natriuretic activity. Intravenous infusion of alpha or beta-MSH
      leads to a time- and dose-dependent natriuresis, whereas gamma-MSH is reported to
      be natriuretic at low doses but antinatriuretic at high doses. The natriuretic
      activity of MSH peptides occurs without change in arterial pressure or renal
      hemodynamics, suggesting a possible direct tubular inhibition of sodium
      reabsorption. Intravenously infused gamma-MSH is associated with an increase in
      the plasma concentration of atrial natriuretic peptide. In addition, gamma-MSH
      also has a direct intrarenal natriuretic action that is dependent on the renal
      nerves. In rats, gamma-MSH-related peptides are involved in the reflex control of
      sodium excretion in situations such as the natriuresis that occurs (a) from the
      remaining kidney after acute unilateral nephrectomy, (b) from the contralateral
      kidney shortly after unilateral ureteral pressure elevation, and (c) after
      unilateral carotid artery traction. POMC-derived peptides (including MSH) are
      modulated in response to salt loading, and alterations in POMC metabolism and
      plasma peptide concentrations have been observed in genetically hypertensive rats
      and during the development of adrenal regeneration hypertension. In addition,
      plasma gamma-MSH levels are elevated in patients with severe congestive heart
      failure, and in primary hyperaldosteronism. These observations suggest a possible
      involvement of MSH-related peptides in sodium homeostasis as well as in certain
      forms of hypertension.

PMID- 7508016
TI  - Physiological significance of Na+/K(+)-ATPase activity in the central nervous
      system and endogenous sodium-pump inhibitors in the neural regulation of arterial
      blood pressure.
AB  - In anesthetized Sprague-Dawley rats, cerebrolateral ventricular administration of
      potassium chloride solutions (KCl, 0.375-1.25 mumol, i.c.v.) produced
      concentration-dependent reductions in the arterial blood pressure and heart rate.
      These responses were significantly attenuated by prior i.c.v.-administration
      ouabain, a selective inhibitor of the Na+ pump, and by endothelin (ET-1), an
      endogenous peptide that is present in the CNS, suggesting that this peptide may
      participate in the neural regulation of arterial pressure via modulation of Na(+)
      pump activity. Although both acute fluid volume expansion and/or osmotic stimulus
      have been shown to facilitate the release of the endogenous Na(+)-pump
      inhibitor(s) into the circulation, only volume expansion significantly attenuated
      the cardiovascular effects of i.c.v. potassium chloride. These observations
      collectively suggest that the Na+, K(+)-ATPase activity in CNS and Na(+)-pump
      inhibitors may play a significant role in the central regulation of arterial
      pressure under certain physiological conditions.

PMID- 7508014
TI  - Immunoreactive endogenous digoxin-like substances: plasma levels are dependent on
      the hypothalamic-pituitary-adrenal axis for release and on kidney function for
      elimination.
AB  - To identify factors that regulate the levels of immunoreactive digitalis-like
      substances (irEDLS) in body fluids, two studies were carried out. Plasma and
      urine levels of irEDLS were measured in uremic and normal subjects. Extracted
      material was fractionated (12 fractions) and assayed by digoxin radioimmunoassay.
      In four fractions, higher levels of irEDLS were found in uremic than in normal
      plasma. Urine from healthy subjects contained very high levels of irEDLS, but in
      urine collected from uremic patients irEDLS levels were similar to those in
      plasma. In another study, eight healthy subjects were given dexamethasone 1 mg
      orally and tetracosactide [an adrenocorticotropic hormone (ACTH) analogue] 0.25
      mg i.v., on separate occasions. Dexamethasone suppressed the plasma and urine
      levels of cortisol and irEDLS. ACTH increased the levels of cortisol in plasma
      and urine, and of irEDLS in plasma. Taken together, these results support the
      hypothesis that irEDLS are of adrenal origin. However, decreased renal clearance,
      rather than increased production or release, may be the main cause of increased
      plasma levels of irEDLS in uremia.

PMID- 7508017
TI  - Cellular mechanisms of action of a ouabain-like factor in vascular smooth-muscle
      cells.
AB  - Ouabain-like factor (OLF) has been implicated to play an important role in
      certain forms of hypertension. We isolated OLF from the urine of salt-loaded
      healthy subjects by stepwise chromatographic procedures. The post-salt fraction
      (F IV) eluted from Sephadex G-25 was rechromatographed on Sephadex G-10. A late
      small-molecular-weight fraction F8 inhibited Na-K-ATPase in vitro (OLF activity).
      The effects of OLF on intracellular Ca2+ concentrations ([Ca2+]i) and pH (pHi)
      were examined in cultures of vascular smooth-muscle cells using the fluorescent
      probes fura-2 and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF),
      respectively. Preincubation with OLF increased basal [Ca2+]i from 87 +/- 6 to 160
      +/- 8 nM (p < 0.001) and enhanced arginine vasopressin-stimulated maximal [Ca2+]i
      (418 +/- 11 vs. 523 +/- 14 nM, p < 0.01). This effect was similar to that of
      ouabain. OLF also induced a rapid transient increase of [Ca2+]i (82 +/- 9 vs. 253
      +/- 23 nM, p < 0.01); [Ca2+]i returned to levels slightly above baseline within
      approximately 4 min. OLF-stimulated [Ca2+]i was attenuated by verapamil (126 +/-
      5 nM, p < 0.01) and was also reduced in Ca(2+)-free medium (104 +/- 9 nM, p <
      0.01). As opposed to OLF, ouabain did not exhibit this fast transient effect on
      [Ca2+]i. Amiloride (10(-3) M) blocked the sustained effect of OLF on [Ca2+]i (77
      +/- 11 vs. 86 +/- 12 nM, NS). OLF induced an increase of pHi from 7.09 +/- 0.03
      to 7.28 +/- 0.04 (p < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508019
TI  - Digoxin-like immunoreactivity may contribute to hyperinsulinemia-associated
      hypertension in patients with glucose intolerance.
AB  - The role of endogenous digitalis-like factors in the pathogenesis of the
      hypertension associated with impaired glucose tolerance was investigated by
      measuring plasma digoxin-like immunoreactivity (DLI). Mean blood pressure
      correlated significantly with the obesity index, serum insulin-like
      immunoreactivity (IRI), and plasma DLI concentrations in subjects with impaired
      glucose tolerance (IGT). Plasma DLI concentrations also correlated significantly
      with the obesity index and serum IRI concentrations. Because increased insulin
      has been proposed to promote sodium reabsorption, sodium retention in turn has
      presumably caused an increase of natriuretic, digitalis-like factors reflected by
      the increased plasma DLI concentrations in patients with IGT. Consequently,
      increased DLI may contribute to the elevated arterial pressure in patients with
      hyperinsulinemia.

PMID- 7508018
TI  - Role of digitalis-like substance in experimental insulin-dependent diabetes
      mellitus hypertension.
AB  - Hypertension is frequently associated with insulin-dependent diabetes mellitus,
      but the mechanism of the hypertension is unknown. An animal model of insulin
      dependent diabetes mellitus hypertension could be helpful in determining the
      mechanism, but experimental insulin-dependent diabetes mellitus has been
      infrequently and irregularly associated with hypertension. In an attempt to
      develop a dependable model of insulin-dependent diabetes mellitus hypertension,
      we studied seven series of rats receiving either streptozotocin, surgical
      reduction of renal mass, or both. We found that superimposing streptozotocin 65
      mg/kg body weight on 25% reduced renal mass regularly produced insulin-dependent
      diabetes mellitus and low-renin volume-expanded hypertension and that the animals
      remained healthy and hypertensive for as long as followed (13 weeks).
      Microalbuminuria correlated temporally with blood pressure. We used this
      dependable model to examine the role of endogenous digitalis-like substance in
      the development of hypertension in insulin-dependent diabetes mellitus. Plasma
      levels of digoxin-like immunoreactive factor (DIF), determined with a digoxin
      radioimmunoassay, were significantly higher in these hypertensive rats than in
      normotensive control rats (two-kidney diabetic rats, 25% reduced renal mass rats
      receiving vehicle for streptozotocin). This increase in plasma DIF was associated
      with a decrease in Na+, K(+)-ATPase activity in microsomes prepared from left or
      right ventricle. Microsomal 5'-nucleotidase, a plasma membrane marker, was
      unchanged. The plasma DIF level correlated inversely with myocardial Na+, K(+)
      ATPase activity and positively with systolic blood pressure.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7508020
TI  - Endogenous digitalis-like activity in the newborn.
AB  - Elevated levels of endogenous digoxin-like immunoreactivity have been reported in
      the body fluids of premature and full-term infants as well as in term pregnancy,
      in the amniotic fluid, and in human milk. Several lines of evidence suggest that
      these factors could also have biological properties in common with digitalis:
      i.e., they could represent truly endogenous digitalis-like factor(s). In recent
      years we succeeded in partially purifying this factor from umbilical cord blood,
      which represents an easily available source of this factor. The inhibitory
      activity of this factor on 86Rb uptake could be neutralized by antidigoxin
      antibodies (Fab fragments) and provided, for the first time, direct evidence of
      an association between digoxin-like immunoreactivity and biological digitalis
      like activity. In addition, these antibodies could be used for immunoaffine
      chromatography as a purification step before separation by high-performance
      liquid chromatography. Preliminary experiments suggest that this endogenous
      compound has both a tissue and an isoenzyme selectivity and is not a well-known
      steroid (testosterone, progesterone, 17-OH progesterone, cortisol,
      dehydroepiandrosterone sulfate, and estradiol).

PMID- 7508021
TI  - Purification and properties of endogenous ouabain-like substances from
      hemofiltrate and adrenal glands.
AB  - Chick embryo heart cells in culture were found to contain two cell types
      differing in their [Ca2+]i. Elevation of [Ca2+]i in cells with 99.4 +/- 7.1 nM
      [Ca2+]i was induced half-maximally at 2 x 10(-9) M ouabain and of cells with 27.9
      +/- 4.4 nM [Ca2+]i at 4 x 10(-8) M ouabain. The localization of a sodium pump
      with differing sensitivity for ouabain in different cell types of the heart
      raised the question of the existence of endogenously formed ouabain. From 6,000 I
      hemofiltrate of uremic patients, a substance of 582 Da cross-reacting with
      ouabain antibodies was purified 42,000-fold. The substance was slightly more
      hydrophobic on a C-18 reversed-phase high-performance liquid chromatography
      (HPLC) than ouabain was. It inhibited 86Rb+ uptake into red blood cells and
      raised like ouabain [Ca2+]i in both types of chick heart cells. From pig adrenal
      glands, a substance inhibiting 86Rb+ uptake into erythrocytes was purified by
      affinity chromatography on a column containing antibodies against ouabain. A
      major part of the eluted substances chromatographed on a C-18-HPLC column as
      ouabain did, but a minor part was somewhat more hydrophobic. It is presumed that
      more than a single endogenous ouabain-like factor exists in mammals.

PMID- 7508022
TI  - Properties of the purified hypothalamic pituitary NA/K-ATPase inhibitor.
AB  - Previously we described the isolation and final purification of an endogenous
      sodium-pump inhibitor from the CNS, mainly from bovine hypothalamus and
      pituitary. The purification protocol consisted of lipophilic chromatography,
      followed by lipid extraction, and semipreparative and analytical reverse-phase
      high-pressure liquid chromatography. The bioassays used were in vitro Na+/K(+)
      ATPase inhibition, and 3H-ouabain displacement from its specific binding site in
      the enzyme structure, as well as inhibition of 86Rb uptake from human red blood
      cells. We have obtained, from both tissues, a low-molecular-weight, nonpeptidic,
      nonlipidic substance that elutes as a single peak highly pure according to
      criteria of coincidence of its spectra properties. When rechromatographed in two
      different chromatographic systems, the same homogeneous peak is obtained
      suggesting complete purity. This pure substance can be isolated from other bovine
      tissues as well as from human plasma and human placenta. It shows a very
      distinctive fluorescence spectrum and it behaves as a potent inhibitor of the
      Ca2+ pump of synaptosomal plasma membrane.

PMID- 7508023
TI  - Effect of ouabain and hypothalamic, hypophysary inhibitory factor on rat
      mesangial cell proliferation.
AB  - The mitogenic effect of a low-molecular-weight, Na+,K(+)-ATPase inhibitory factor
      isolated from bovine hypothalamus and hypophysis (hypothalamic hypophysary
      inhibitory factor, HHIF) and ouabain on cultured rat mesangial cells was
      examined. Ouabain induced a potent stimulation of the [3H]thymidine incorporation
      to DNA, ranging from threefold for a dose of 10(-7) M to seven times for 10(-5)
      M. The amount of proteins per well also increased in a dose-dependent way, which
      was already significant from basal values for the lower dose used. HHIF also
      induced a dose-dependent stimulation of [3H]thymidine incorporation into DNA,
      ranging from 1.7 times for a concentration of 0.02 U/ml to 4.5 times for the
      concentration of 2 U/ml. The amount of protein per well also increased with HHIF,
      but the increase was significant only for the higher dose used. These data allow
      us to conclude that HHIF could play a role in the vascular hypertrophy that is
      associated with the pathogenesis of hypertension.

PMID- 7508024
TI  - Digitalis-like factor and ouabain-like compound in plasma of volume-expanded
      dogs.
AB  - Previous studies demonstrated that ouabain-like compound (OLC) is widely
      distributed in mammalian species and is found in a variety of different tissues.
      Although much evidence suggests that OLC is endogenous to mammals, little
      information is available concerning physiological and/or pathophysiological roles
      for OLC. In this study, generic endogenous digitalis-like factor (E-DLF) was
      measured using an enzyme bioassay and the more specific OLC was determined using
      ouabain antisera in plasma drawn from dogs before and 30 and 120 min after
      massive volume expansion with isotonic saline. Plasma OLC was not changed by the
      saline load, whereas Na excretion was significantly elevated at the 30-min blood
      draw and remained elevated at the 120-min blood draw. Because renal exposure to
      OLC did not change with saline loading, it is unlikely that any portion of the
      profuse natriuresis in these animals could be attributed to OLC. In contrast,
      plasma E-DLF was higher after the saline load than before in each of four dogs at
      30 and 120 min after the infusion. What portion of the profuse natriuresis can be
      attributed to E-DLF is unknown, although it is reasonable to assume that
      nanomolar levels of pump inhibitor contributed to the natriuresis to some degree.

PMID- 7508025
TI  - Effect of hypothalamic lesions on interaction of centrally administered ANF and
      the circulating sodium-pump inhibitor.
AB  - We investigated the possible central interaction of atrial natriuretic factor
      (ANF) and an endogenous Na+, K(+)-ATPase (Na-pump) inhibitor in normal rats.
      Release of an endogenous Na-pump inhibitor associated with deoxycorticosterone
      acetate-salt hypertension may be regulated in the anteroventral third ventricle
      (AV3V) area of the CNS. We reported earlier that bolus injection of synthetic 26
      amino acid ANF (Arg101-Tyr126, 6 micrograms/250 g rat) into the lateral brain
      ventricle (ICV) promotes the appearance in the plasma of a Na-pump inhibitor in
      rats. To determine whether the AV3V area of the brain is involved in the ICV
      effect of ANF, we introduced electrolytic lesions in this area. This treatment
      abolished the appearance of the Na-pump inhibitor after intraventricular
      injection of ANF. To further localize the area and the pathways involved in the
      interaction of ANF and the Na-pump inhibitor, we produced bilateral medial
      coronal knife cuts designed to transect the medially coursing pathway through the
      periventricular tissue of the AV3V region between the level of the medial
      preoptic area and the anterior hypothalamic nuclei. These knife cuts also
      abolished the appearance of the Na-pump inhibitor after ICV injection of ANF. Our
      data to date indicate that centrally administered ANF promotes the appearance of
      a Na-pump inhibitor in the plasma. A central site of interaction between ANF and
      the Na-pump inhibitor appears to be the AV3V area and a medial pathway coursing
      caudally from the AV3V region.

PMID- 7508026
TI  - Hypothalamic Na+,K(+)-ATPase inhibitor constricts pulmonary arteries of
      spontaneously hypertensive rats.
AB  - Hypothalamic inhibitory factor (HIF) is an endogenous high-affinity inhibitor of
      Na+,K(+)-ATPase with ouabain-like properties and has been implicated in the
      pathogenesis of genetic systemic hypertension. We wondered whether HIF might also
      be associated with the recently demonstrated pulmonary hypertension of
      spontaneously hypertensive rats (SHRs). We compared HIF effects on the
      contractility of isolated 2- to 3-mm pulmonary artery (PA) rings from SHRs and
      age-matched normotensive Sprague-Dawley (SD) rats. HIF caused a reversible,
      concentration-dependent increase in tension in PA rings of SHR and SD rats,
      whereas ouabain did not. PA tension development with HIF (4 nM final
      concentration) was significantly higher in SHRs than in SD rats: 308 +/- 56 mg
      (mean +/- SE) vs. 137 +/- 26, respectively, p < 0.05. Abdominal aortic
      contractions induced by HIF did not differ between SHRs and SD rats. In SHRs, but
      not SD rats, the effect on PA rings was significantly greater than on aortic
      rings. In all cases, contraction was abolished by phentolamine but was unaffected
      by calcium-channel blockade using verapamil. HIF-induced tension development
      required external Ca2+. We conclude that PA rings from SHRs are more sensitive to
      Na+,K(+)-ATPase inhibitory effects of HIF than PA rings from SD rats, which may
      contribute to the observed pulmonary hypertension in SHR. Local modulation of the
      Na+,K(+)-ATPase-adrenergic neuroeffector interaction may be the vasoconstrictive
      mechanism of action of HIF in these vessels.

PMID- 7508027
TI  - A novel endogenous sodium-pump inhibitor in pig urine: purification and
      comparison with the inhibitor purified from bovine adrenal glands.
AB  - To clarify the chemical nature and pathophysiological significance of an
      endogenous, specific Na-pump inhibitor, extracts of various tissues have been
      examined. The activities were extracted by an Amberlite XAD-2 adsorbent and
      fractionated by high-performance liquid chromatography (HPLC) on an ODS column.
      Among many tissues and fractions tested, the extract of pig urine has been found
      to contain a large amount of 86Rb uptake inhibitory activities. The strongest
      inhibitory activity for 86Rb influx into erythrocytes also exhibited a cross
      reactivity with anti-ouabain antibodies. This activity has been purified to
      homogeneity using five steps of reverse-phase HPLC. Although most of the dose
      response curves for this purified Na-pump inhibitor, designated as uroxin, in the
      various assay systems paralleled those of ouabain and the inhibitor purified from
      bovine adrenal glands (designated as adrexin C), the cross-reactivity curve with
      anti-ouabain antibodies did not. The retention time of uroxin on an ODS HPLC
      column was also different from that of digoxin, ouabain, or adrexin C. 1H nuclear
      magnetic resonance spectroscopic study suggests that uroxin is a novel Na-pump
      inhibitor that is structurally different from any of the known cardiotonic
      steroids or the substances previously reported to exhibit Na-pump inhibitory
      activity. Thus, uroxin may be a new type of endogenous regulator for the Na pump.

PMID- 7508028
TI  - Use of two-sided bifunctional liposomes in the study of a hypothalamic Na,K
      ATPase inhibitor.
AB  - Two-sided bifunctional (ATP-filled) Na,K-ATPase liposomes have been developed as
      a result of knowledge about the average liposome diameter and volume, the
      liposome size distribution, the average number of Na,K-ATPase molecules
      reconstituted per liposome, and the orientation of the reconstituted Na,K-ATPase
      molecules. The addition of 5-10 microM external 86Rb to the liposomes containing
      50 mM encapsulated ATP provoked an impressive 86Rb accumulation by the cell-like
      oriented pumps. The successive addition of external ATP activated the pumps in
      the reversed orientation of the same liposome, leading to total extrusion of the
      previously accumulated 86Rb. An inhibitor extracted from bovine hypothalamus
      (hypothalamic inhibitory factor) inhibited the cell-like-oriented population,
      i.e., acted like an extracellular inhibitor at 30 nM. Conversely, at 75 nM, the
      reversed pump population was also blocked, indicating that the inhibitor either
      transversed the membrane or was able to act also at the intracellular enzyme side
      at a higher concentration. Thus, the side of action as well as the membrane
      permeability of structurally unknown endogenous Na,K-ATPase inhibitors can be
      determined simultaneously in a single suspension of two-sided bifunctional Na,K
      ATPase liposomes.

PMID- 7508029
TI  - Volume expansion in renal failure patients: a paradigm for a clinically relevant
      [Na,K]ATPase inhibitor.
AB  - A volume-sensitive inhibitor of [Na,K]ATPase, termed the digitalis-like factor
      (DLF), is postulated to participate in hypertension. To test this hypothesis, end
      stage renal failure patients on peritoneal dialysis were placed on a clinical
      protocol that brought about a gradual, sustained volume expansion. This was
      accompanied by significant increases in body weight (4.1 +/- 1.2 kg, p < 0.05),
      mean arterial pressure (18.2 +/- 6.4 mm Hg, p < 0.05), and serum DLF activity
      (4.7 +/- 1.9% inhibition, p < 0.05). Processing these patients' daily dialysates
      by ultrafiltration and high-performance liquid chromatography allowed for the
      identification of a single elution fraction having volume-sensitive [Na,K]ATPase
      inhibitory activity. This factor in turn was correlated with serum DLF activity
      (R = 0.60, p = 0.002), weight gain (R = 0.67, p = 0.0003), and mean arterial
      pressure (R = 0.59, p = 0.003). This factor was readily distinguished from
      ouabain and digoxin but was similar to the DLF isolated from amniotic fluid.
      These results suggest that volume expansion in renal failure patients on
      peritoneal dialysis gives rise to a unique volume-sensitive DLF that may
      contribute to these patients' increase in blood pressure.

PMID- 7508031
TI  - An intestinal natriuretic factor.
AB  - In 1975, reports were published that suggested that the gastrointestinal tract
      can "taste" the intake of sodium and in some unknown way influence the kidneys to
      increase sodium excretion. To test whether the intestine contained a natriuretic
      factor, intestinal tissue from cats was homogenized and fractionated by
      ultrafiltration to a molecular range of approximately 500-10,000 Da and separated
      by gel chromatography (Sephadex G25). The fractions were pooled into four large
      fractions that were assayed for "natriuretic" activity on anesthetized rats. The
      fraction containing the material with an apparent molecular mass of 500-1,000 Da
      augmented renal excretion of sodium and water, whereas the other pooled fractions
      did not exhibit any consistent natriuretic effect. The "natriuretic" fractions
      from gel filtration were further purified by ion exchange chromatography using a
      cation exchanger. The natriuretic activity was eluted from the ion exchange
      chromatography column at a NaCl concentration of 250 mM. Preliminary experiments
      on Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) suggest that
      the intestinal influence on renal sodium excretion is more pronounced in SHR than
      in WKY rats.

PMID- 7508032
TI  - Endogenous natriuretic factors. 2: Characterization of natriuretic and
      vasopressive substances from human uremic urine.
AB  - It is our intention to isolate, purify, and characterize the putative low
      molecular-weight "natriuretic hormone" responsible for extracellular fluid (ECF)
      homeostasis. Toward this end, we are purifying from human uremic urine, and
      identifying endogenous vasopressor and natriuretic compounds. Bioactive
      components from large volumes of pooled urine were purified by ultrafiltration (<
      or = 3 kDa), gel filtration chromatography, and sequential reverse-phase and
      normal-phase high-performance liquid chromatography (HPLC). After each HPLC step,
      the fractions were evaluated in vivo, were assayed for inhibition of Na+/K(+)
      ATPase-mediated 86Rb+ uptake, and were checked for cross-reactivity with an anti
      ouabain antibody. Fractions assayed in vivo were identified that induced
      natriuresis, altered mean arterial pressure, or increased plasma cyclic-GMP.
      Also, many fractions inhibited Na+/K(+)-ATPase and/or cross-reacted with anti
      ouabain antibody. None of the in vitro assays correlates with natriuretic or
      pressor effects. This plethora of bioactivities, revealed only with increased
      sample purity, may account for much of the confusion and multiplicity of crude
      isolates claimed to be the putative hormone. Presently we are attempting to
      purify and identify these natriuretic materials. One of these, a 3-substituted
      indole, has been partially characterized.

PMID- 7508030
TI  - Digitalis-like factors from human urine.
AB  - We isolated two candidates for endogenous digitalis-like factors from human urine
      based on the inhibition of [3H]ouabain binding to intact human erythrocytes. The
      more-polar ouabain-displacing compound-1 (ODC-1) closely resembled ouabain in
      biological, physicochemical, and chromatographic properties. Moreover, anti
      ouabain IgG dose-dependently neutralized the action of ODC-1. The less-polar ODC
      2 behaved identically to digoxin in three analytical high-performance liquid
      chromatography and thin layer chromatography systems. Fast atom bombardment mass
      spectrum and proton nuclear magnetic resonance spectrum supported the notion that
      ODC-2 may be indistinguishable from digoxin. The possibility that substances
      quite similar to cardenolides are synthesized in the mammalian body must be
      seriously considered.

PMID- 7508034
TI  - Alterations of K+ transport by the alpha 1 Na(+)-K+ pump in red blood cells of
      the Dahl salt-sensitive rat.
AB  - We studied the kinetic properties of the Na(+)-K+ pump in rat red blood cells
      (RBCs) of the Dahl salt-sensitive (DS) and salt-resistant (DR) strains by
      measuring unidirectional ouabain-sensitive (OS) Na+ and K+ fluxes (mmol/L cell x
      h = FU, mean +/- SE) and varying internal (i) and external (o) Na+ and K+
      concentrations. OS Na+ efflux into Nao 140 mM, Ko 5 mM was similar in both
      strains in fresh cells as well as for Vmax and Km for Nai. However, DS pumps have
      significantly lower K+ influx than DR pumps in fresh cells, thereby giving rise
      to a higher Na:K coupling ratio. The lower rates of K+ influx were caused by a
      defective activation by Nai and Nao that led to significantly lower Vmax than in
      DR pumps. The activation of K+ influx by Ko in the presence of 140 mM Nao had a
      lower Vmax and a higher affinity in DS (Vmax 2.58 +/- 0.09 FU, n = 17, Km 0.63 +/
      0.23 mM) than in DR rats (Vmax 4.7 +/- 0.3 FU, n = 16; Km 1.9 +/- 0.2 mM).
      However, when Nao was removed, these two kinetic parameters became similar in
      both strains. OS 86Rb/K efflux from fresh RBCs was significantly higher in DS
      than in DR rats, because the K50 from Nai inhibition was threefold higher in DS
      pumps. In summary, the low rates of unidirectional and net K+ influx in DS cells
      are caused by impaired Nai and Nao activation as well as the high values of K+
      efflux are caused by low affinity for Nai inhibition.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508035
TI  - Role of brain ouabain-like activity in the central effects of sodium in rats.
AB  - To evaluate whether changes in central ouabain-like activity (OLA) play a role in
      the effects of dietary sodium on sympathetic outflow and blood pressure (BP), the
      effects of high vs. control sodium intake on BP, brain OLA, and responsiveness to
      exogenous ouabain were studied in young spontaneously hypertensive rats (SHRs)
      vs. Wistar-Kyoto (WKY) rats. At 4 weeks of age, the BP of SHRs was already
      significantly increased compared with that of WKY rats, and hypertension
      developed further with maturation. High sodium intake exacerbated the
      hypertension. Compared with WKY rats, in SHRs OLA in the hypothalamus was already
      increased at 4 weeks of age. High sodium intake increased brain OLA in both SHRs
      and WKY rats. However, high dietary sodium decreased pressor and
      sympathoexcitatory responses to exogenous ouabain only in SHRs. These results may
      indicate that in WKY rats on control sodium, endogenous OLA already exerts its
      maximal central effects and a further increase in OLA by high sodium intake does
      not cause hemodynamic changes, whereas in young SHRs the increase in brain OLA by
      high sodium intake may play a functional role in the pressor and
      sympathoexcitatory responses to high sodium.

PMID- 7508033
TI  - Comparison of low-molecular-weight plasma and urine Na-K-ATPase
      inhibitors/hypertensive factors.
AB  - Two highly purified low-molecular-weight (< 500 Da) Na-K-ATPase inhibitors, one
      originating from human plasma and the second from human urine, which both eluted
      in the identical locus from a C18 reversed-phase high-pressure liquid
      chromatography (HPLC) column, were compared with respect to (a) K effect on Na-K
      ATPase inhibition; (b) displacement of [3H]ouabain from binding sites on purified
      hog brain Na-K-ATPase; (c) cross-reactivity with digoxin antibodies; and (d)
      vasoconstrictor effects in isolated rabbit femoral arteries. Inhibition of Na-K
      ATPase by the plasma factor correlated inversely with K concentration, whereas
      inhibition by the urine factor correlated directly with K concentration. In the
      absence of K, the plasma factor displaced [3H]ouabain from both high- and low
      affinity binding sites, whereas the urine factor displaced [3H]ouabain only from
      the low-affinity binding site. Neither factor possessed digoxin-like
      immunoreactivity. Both factors acted as direct vasoconstrictors, and potentiated
      the vasoconstrictor action of norepinephrine. The degree of vasoconstriction
      caused by the plasma factor diminished progressively with added K, indicating
      that the vasoconstrictor effect of this factor was mediated by the Na-K-ATPase
      pump. Thus, although both the plasma and urine Na-K-ATPase inhibitors are
      vasoconstrictors, their mechanisms of action are different.

PMID- 7508036
TI  - Characteristics of a ouabain-like factor from Milan hypertensive rats.
AB  - Ouabain-like factor (OLF) has been extracted from hypothalamus and adrenal glands
      of the ox and rats of the Milan hypertensive strain (MHS) and their normotensive
      controls (MNS). OLF was identified by its ability (a) to inhibit ouabain
      sensitive 86Rb uptake into human erythrocytes, (b) to displace [3H]ouabain
      binding, and (c) to inhibit purified dog kidney Na-K-ATPase. Rat and bovine OLF
      have similar characteristics. Those that are close to ouabain are (a) ligand
      conditions for maximal inhibitory activity, (b) high-performance liquid
      chromatography retention time, (c) reversibility of inhibitory activity on Na-K
      ATPase, (d) reduced Na-K-pump inhibitory activity by K+, (e) high affinity for Na
      K-ATPase, and (f) no activity on Ca(2+)-ATPase. OLF does not resemble ouabain
      because the capacity of OLF to inhibit ouabain low-affinity Na-K-ATPase isoform
      is greater than that of ouabain. The yield of OLF is greater from MHS than MNS
      hypothalamic and adrenal extracts. These findings represent the first direct
      evidence that a higher amount of OLF is present in tissues from genetically
      hypertensive rats than from their inbred normotensive controls, maintained under
      the same dietary and environmental conditions. This further supports previous
      observations on the role of OLF in the pathogenesis of MHS hypertension.

PMID- 7508038
TI  - On the role of digoxin-like substances, ANP, and AVP in natriuresis induced by
      hypertonic saline infusion in dogs.
AB  - The increase of sodium concentration in cerebrospinal fluid or in plasma triggers
      the osmoregulatory mechanism, namely, the enhancement of renal free-water
      reabsorption and natriuresis. The increase of free-water reabsorption has been
      recognized for many years as a consequence of the osmotically released
      vasopressin (AVP). However, the control of renal sodium excretion in the
      mechanism of osmoregulation has not been clarified It has been suggested to be,
      at least in part, of hormonal nature, implying the decreased release of
      aldosterone and the increased release of atrial natriuretic peptide (ANP),
      digoxin-like substances (DLIS), and AVP. Neither of these factors, however, has
      been unequivocally linked to the mechanism of immediate natriuresis caused by an
      acute increase in cerebrospinal fluid or plasma sodium concentration. It was
      reconfirmed in our present experiments in anesthetized dogs that aldosterone,
      ANP, and DLIS could hardly play a role in the immediate natriuresis after the
      i.v. infusion of hypertonic saline (20% NaCl solution infused in 20 min in an
      amount that was 0.13% of body weight). However, the role of AVP in this type of
      natriuresis seems more promising as a V1/V2 receptor antagonist applied i.v.
      before the hypertonic saline loading completely prevented the increase of renal
      sodium excretion. Natriuresis after the isotonic saline load was not impaired by
      the same antagonist of vasopressin receptors.

PMID- 7508037
TI  - Effects of phospholipids on renal function.
AB  - The effects of two classes of phospholipids (PL) on renal function have been
      studied. Bolus injections of 1 ng (10 pmol) of lysophosphatidylcholine (LPC)
      caused natriuresis and diuresis in rats. Natriuretic activity was eliminated by
      substituting unsaturated bonds in the 1-acyl group and by removing the choline
      group on the sn-3 position. Natriuretic activity was not affected by substitution
      of 1-alkyl for 1-acyl groups. In the dog, LPC was natriuretic when given as a
      bolus of 3.0 micrograms/kg or as a constant infusion at 5 ng/kg/min. To explore
      further the effect of alkyl PLs on renal function, a series of studies with
      platelet activating factor (PAF) was performed. PAF injected directly into the
      renal artery (IR) in bolus doses of 0.5-10 ng/kg caused renal vasodilation that
      was blocked by a specific PAF receptor antagonist. This effect was not due to
      release of vasodilatory eicosanoids, dopamine, or nitric oxide (NO). PAF given IR
      as a continuous infusion at 2.5 ng/kg/min attenuated the renal vasoconstrictor
      effects of angiotensin II and norepinephrine but not vasopressin. This effect to
      attenuate vasoconstriction was blocked by the NO inhibitor N-monomethyl-L
      arginine. These studies using picomolar amounts of PL suggest a physiologic role
      for these compounds in control of renal function.

PMID- 7508039
TI  - Is urodilatin (rather than atriopeptin) the primary natriuretic peptide of the
      ANP family?
AB  - This article summarizes evidence supporting the hypothesis that urodilatin,
      rather than atriopeptin, is the member of the atrial natriuretic peptide family
      primarily involved in the regulation of renal sodium excretion. A number of lines
      of evidence imply that atriopeptin is only of trivial importance in the
      regulation of sodium excretion during normal living conditions. On the other
      hand, urodilatin, which is produced in the kidneys, has properties very similar
      to atriopeptin. Moreover, its excretion in the urine appears to correlate quite
      closely with the concomitant excretion of sodium.

PMID- 7508040
TI  - Is the renal natriuretic peptide urodilatin involved in the regulation of
      natriuresis?
AB  - Recent evidence has shown that the kidneys produce and secrete a member of the
      atrial natriuretic peptide family, named urodilatin. This 32-amino acid peptide
      does not circulate in blood, but is secreted into urine. Urodilatin excretion
      closely parallels renal sodium excretion under various conditions that influence
      body fluid regulation, such as circadian rhythm, salt ingestion, acute
      intravenous sodium loading, water immersion, atrial distension, and cerebral
      hypernatremia. In contrast, the plasma concentration of the atrial member of the
      natriuretic peptide family often is only weakly and occasionally even negatively
      associated with natriuresis under these conditions. We conclude from these
      observations that urodilatin rather than atrial natriuretic peptide might be the
      member of the natriuretic peptide family that is involved in the regulation of
      natriuresis in normal physiology.

PMID- 7508041
TI  - Natriuretic effects of dopamine agonist drugs in models of reduced renal mass.
AB  - In addition to recognized neurotransmitter properties in the central nervous
      system, dopamine (DA) plays a role in the physiological activity of the kidney
      through its hemodynamic and natriuretic effects. On the basis of these data, some
      pharmacological interventions have focused their attention on the use of DA
      related drugs to improve renal sodium handling. We summarize the data obtained
      from two studies using two DA agonist drugs, lisuride (LIS) and fenoldopam (FEN),
      in two situations of reduced renal mass. During an intravenous sodium load
      performed on 10 uninephrectomized dogs, LIS induced a significant blockade of the
      concomitant pressor response, estimated by lower blood pressure and
      norepinephrine levels. Under these same conditions, FEN significantly decreased
      blood pressure and elevated the natriuretic response. In a second study, when FEN
      was administered at nonhypotensive doses to chronic renal failure patients, it
      evoked an enhancement of diuresis, natriuresis, and creatinine clearance. These
      data seem to confirm the involvement of DA in the regulation of cardiovascular
      homeostasis and its role in renal sodium handling. Furthermore, these beneficial
      effects support the use of DA-related drugs in the field of hypertension.

PMID- 7508042
TI  - Pharmacological characterization of the activity of endogenous inotropic factor
      from porcine left ventricle.
AB  - We report some of the unique pharmacological properties of a semipurified
      endogenous inotropic factor (EIF) present in the extract of the porcine left
      ventricle. EIF produced the following effects: (a) increase in isometric
      contractile force developed by electrically driven canine right ventricular
      trabecula, reaching a maximum with 60-100 microliters/ml concentration; (b)
      inhibition of Na-pump activity in canine portal vein; (c) no digitalis-like
      cardiac toxicity, e.g., increased diastolic tension or spontaneous diastolic
      mechanical oscillatory activity, despite inhibition of the sodium pump; (d) a
      small increase in sarcoplasmic reticular Ca release from the heart but a large
      increase in transsarcolemmal Ca influx as seen in biphasic contractions, an
      action similar to that produced by digitalis-like substances; and (e)
      prolongation of the action potential duration and refractory period of the canine
      isolated trabeculae. This latter action may confer a unique antiarrhythmic
      property to EIF.

PMID- 7508043
TI  - Na+, K(+)-ATPase and Na+/Ca2+ exchange isoforms: physiological and
      physiopathological relevance.
AB  - Different isoforms of the (Na+ + K+)-ATPase are expressed in different cell types
      in which they contribute to specialized properties. Their biochemistry and
      physiology are complex. These isozymes vary in their sensitivity to cardiac
      glycosides and to intracellular Na+ and Ca2+ concentrations. Their functional
      expression at the membrane level in the different parts of kidney, heart, and
      brain varies with species and during ontogenesis. In rat heart, at birth and
      postpartum, there are quantitative and qualitative changes in the expression of
      the (Na+ + K+)-ATPase and Na+/Ca2+ exchange isoforms. The (Na+ + K+)-ATPase
      isozymes react differently to hormonal regulation and to physiopathological
      alterations, i.e., cardiac ischemia and cardiac hypertrophy. Considering the
      diversity of the (Na+ + K+)-ATPase isoforms and their numerous regulations, what
      could be the targets of endogenous (Na+ + K+)-ATPase inhibitors?

PMID- 7508044
TI  - Endothelial modulation of the vascular sodium pump.
AB  - Endothelial interference with ouabain effects on vascular smooth muscle was
      analyzed in isolated human placental arteries and veins, carotid arteries from
      reserpinized guinea pigs (to eliminate the adrenergic actions of the glycoside),
      and aorta from Wistar-Kyoto (WKY) rats that were 5 weeks, 3, 6, 12, and 18 months
      old. After endothelium removal, ouabain-evoked contractions were increased in
      human placental vessels and guinea pig carotid arteries. These effects were not
      mimicked by the blockade of nitric oxide, prostaglandin, or leukotriene
      synthesis. Bioassay experiments suggest the release of an endothelial diffusable
      factor(s). 86Rb+ uptake, a method to measure sodium-pump activity, was
      significantly reduced by the removal of endothelium. In aortas from WKY rats,
      ouabain caused contractions that were increased with the age of animals until 12
      months. Endothelium removal increased ouabain effects in vessels from animals of
      3 and 6 months but not in older ages. These results suggest (a) that there is an
      inhibitory endothelial modulation of ouabain-induced vasoconstriction by the
      release of a diffusible factor(s); (b) that this substance is not related to
      nitric oxide, prostaglandins, or leukotrienes; (c) that its mechanism of action
      could be stimulating the activity of vascular sodium pump and/or antagonizing its
      inhibition by ouabain; and (d) that the endothelial modulation is lost in the
      elderly.

PMID- 7508045
TI  - Vascular renin-angiotensin system and vascular protection.
AB  - Vascular angiotensin plays an important role in the long-term regulation of the
      blood vessel function and structure. Angiotensin stimulates vascular smooth
      muscle cell growth via the induction of protooncogene and autocrine growth factor
      gene expressions. In hypertension, atherosclerosis and restenosis, vascular
      angiotensin activity is increased and participates in the pathobiology of these
      vascular diseases. Experimental data demonstrate that angiotensin-converting
      enzyme inhibitors can prevent vascular hypertrophy of hypertension, attenuate
      atherosclerosis, and inhibit neointimal hyperplasia of restenosis. Taken
      together, the data show that pharmacologic blockade of the vascular renin
      angiotensin system may result in vascular protection. Ongoing clinical trials
      (MERCATOR, QUIET) will address the relevance of these experimental observations
      in clinical therapy.

PMID- 7508047
TI  - Different effects of angiotensin-converting enzyme inhibition in human arteries
      and veins.
AB  - The renin-angiotensin system (RAS) participates in the regulation of vascular
      tone; its effects were studied in human internal mammary artery (IMA) and
      saphenous vein (SV) suspended in organ chambers for isometric tension recording.
      The angiotensin-converting enzyme (ACE) inhibitor enalaprilat (10(-7) M) markedly
      augmented endothelium-dependent relaxations to bradykinin in SV (concentration
      shift: 10-fold; n = 6; p < 0.005), but not in IMA; in both blood vessels, it had
      no effect on endothelium-dependent relaxations to acetylcholine. The contractions
      to angiotensin I (Ang I; 10(-7) M) were markedly inhibited by enalaprilat (10(-7)
      M) in SV (control: 34 +/- 6% of 100 mM KCl; treatment: 18 +/- 6%; n = 7; p <
      0.05) but not in IMA (control: 33 +/- 4%; treatment: 30 +/- 6%; n = 7; NS) and
      abolished by the Ang II receptor antagonist DuP 753 (10(-7) M) in both blood
      vessels. Ang II (10(-7) M) induced more pronounced contractions than Ang I in IMA
      (63 +/- 4%) and SV (63 +/- 5%; n = 5-6; p < 0.05 vs. Ang I), which was markedly
      inhibited by DuP 753 (10(-7) M; IMA: 21 +/- 5%; SV: 32 +/- 5%; p < 0.05). Thus,
      in SV but not IMA, ACE inactivates bradykinin and thereby blunts endothelium
      dependent relaxations to the peptide and converts Ang I to Ang II.

PMID- 7508046
TI  - Endothelium-dependent effects of converting-enzyme inhibitors.
AB  - Angiotensin-converting enzyme (ACE) inhibitors were designed to prevent the
      vasoconstrictor influence of the activated renin-angiotensin system. However, it
      has long been suspected that the vasodilator actions of these compounds are not
      entirely related to inhibition of the generation of angiotensin II. Bradykinin,
      which is rapidly degraded by ACE, stimulates the release of endothelium-derived
      vasodilator mediators, including nitric oxide, endothelium-derived
      hyperpolarizing factor, and prostacyclin. These mediators do not contribute to
      the vasodilator effect of bradykinin in every arterial bed. However, the
      prevention by ACE inhibitors of the degradation of bradykinin-induces an
      augmentation of the production of these substances and thus potentiates the
      dilatation evoked by the peptide. The existence of a local kallikrein-kinin
      system in the vascular wall has been demonstrated, and locally generated kinins
      contribute to the acute vasodilator actions of ACE inhibitors. ACE inhibitors can
      potentiate endothelium-dependent dilatations evoked by neurohumoral mediators
      that are not substrates for ACE. Thus, the vasodilator properties of ACE
      inhibitors not only reflect inhibition of the renin-angiotensin system but also
      depend on the enhanced production of endothelium-derived mediators.

PMID- 7508048
TI  - Effect of cilazapril and indomethacin on endothelial dysfunction in the aortas of
      spontaneously hypertensive rats.
AB  - Chronic hypertension is associated with impaired endothelial function [i.e.,
      reduced synthesis/release of endothelium-derived relaxing factor (EDRF) and
      increased synthesis/release of endothelium-derived contracting factor (EDCF)] in
      both animals and humans. Although it is not known whether endothelial dysfunction
      is the consequence and/or an important pathogenetic cause of hypertension, the
      goal of effective antihypertensive therapy should include restoration of normal
      endothelial function as well. Because angiotensin I-converting enzyme (ACE)
      inhibitors are effectively used in the treatment of hypertension, the aim of the
      present study was to test whether in vivo treatment of spontaneously hypertensive
      rats (SHRs) with the ACE inhibitor cilazapril improves endothelial function in
      the isolated thoracic aorta of SHRs. Treatment of SHRs with cilazapril (10
      mg/kg/day orally for 2 weeks) resulted in a significant decrease in blood
      pressure and normalization of endothelium-dependent relaxation evoked by
      acetylcholine (ACh) and adenosine diphosphate (ADP). However, cilazapril
      treatment had no significant effect on endothelium-dependent contractions evoked
      by 5-hydroxytryptamine (5-HT; serotonin) and prostaglandin F2 alpha (PGF2 alpha).
      In contrast, in vitro treatment of isolated thoracic aortas with indomethacin
      (10(-5) M) normalized endothelium-dependent relaxations to ACh and ADP as well as
      inhibited endothelium-dependent contractions to 5-HT and PGF2 alpha. These
      results suggest that the ACE inhibitor cilazapril increases the synthesis/release
      of EDRFs whereas indomethacin prevents the synthesis/release of cyclo-oxygenase
      derived EDCFs in the endothelium of rat aorta. The exact mechanism of action of
      ACE inhibitors on endothelial dysfunction remains to be determined.

PMID- 7508049
TI  - Endothelium-derived bradykinin: implications for angiotensin-converting enzyme
      inhibitor therapy.
AB  - The effects of angiotensin-converting enzyme (ACE) inhibitors on endothelial
      autacoid formation were determined in human cultured endothelial cells and in
      endothelium-intact bovine coronary arteries under resting conditions and after
      stimulation with bradykinin. Incubation of cultured human endothelial cells with
      moexiprilat or ramiprilat (0.3 microM) caused a maintained increase in resting
      intracellular calcium [Ca2+]i, which was prevented by the selective B2-receptor
      antagonist Hoe 140 (0.1 microM). Both ACE inhibitors also significantly enhanced
      the increase in [Ca2+]i elicited by bradykinin (3 nM). In parallel with their
      effect on resting [Ca2+]i, moexiprilat and ramiprilat both induced an increase in
      intracellular cyclic GMP (cGMP). This increase was prevented by Hoe 140 (0.1
      microM) and was abolished by NG-nitro-L-arginine (30 microM), indicating a kinin
      induced nitric oxide (NO) formation in this response. The elevation in [Ca2+]i
      also led to an enhanced production of prostacyclin (PGI2), as indicated by an
      increase in the concentration of 6-keto prostaglandin F1 alpha (PGF1 alpha) in
      the cell supernatant. Similar effects of the ACE inhibitors on endothelial
      autacoid production were observed in endothelium-intact bovine coronary arteries.
      Like bradykinin (30 nM), moexiprilat (0.3 microM) elicited a nearly twofold
      increase in the cGMP content of these arteries, which was abolished by both NG
      nitro-L-arginine and removal of the endothelium. The functional consequences of
      this ACE inhibitor-induced increase in vascular cGMP were reflected by a distinct
      relaxation of arteries preconstricted with PGF2 alpha.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508050
TI  - Peptide vasoconstrictors, vessel structure, and vascular smooth-muscle
      proliferation.
AB  - The peptide vasoconstrictors angiotensin II (Ang II) and endothelin-1 (ET-1),
      originally thought to derive exclusively from the plasma renin-angiotensin system
      and vascular endothelium, respectively, have been demonstrated to be produced
      independently of such sources. Local tissue angiotensin-generating systems are
      well documented, and endothelin production has been demonstrated for a variety of
      nonendothelial cells, including vascular smooth-muscle cells (VSMC). There is
      increasing evidence from in vitro studies that local production of these
      vasoconstrictor peptides may contribute to blood vessel homeostasis and the
      development of vascular pathologies. Results obtained from pharmaceutical
      intervention in humans and animals of these systems strongly support this
      hypothesis. In addition to their vasoconstrictor properties, Ang II and ET-1 act
      as potent biological effectors. In vitro, both vasoconstrictor peptides appear to
      modulate the activity of autocrine feedback loops in VSMC. The activity of these
      feedback loops in vivo may represent a central mechanism for regulation and
      phenotypic differentiation of this cell type. The best-recognized autocrine
      feedback loops of VSMC are constituted by platelet-derived growth factor and
      transforming growth factor-beta, both of which are influenced by the action of
      Ang II and ET-1. Because both vasoconstrictors (via their induction of autocrine
      growth modulators) may influence the composition of the extracellular matrix of
      VSMC, the effects of the peptide vasoconstrictors on the (auto-) regulated
      feedback loops are of long-term structural importance. Ang II and ET-1 promote
      the synthesis and secretion of the glycoproteins thrombospondin, fibronectin, and
      tenascin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508051
TI  - Resistance vessel structure in hypertension: growth or remodeling?
AB  - Essential hypertension is associated with alterations in the structure of the
      resistance vessels such that the ratio of the media thickness to the lumen
      diameter (media: lumen ratio) is increased. This altered structure need not,
      however, be associated with growth but could be due to a rearrangement of a
      normal amount of material around a smaller lumen, a process called "remodeling."
      This article reviews evidence for the relative contributions of growth and
      remodeling regarding subcutaneous resistance arteries taken from patients with
      essential hypertension and mesenteric resistance arteries taken from transgenic
      hypertensive rats. The results suggest that in both cases, the increased
      media:lumen ratio is due more to remodeling than to growth. These data therefore
      raise some doubts as to whether growth factors play an important role in the
      etiology of essential hypertension.

PMID- 7508053
TI  - A Diuretic Specifically Designed for Treating Hypertension: Current Insights.
      Proceedings of a satellite symposium to the 14th scientific meeting of the
      International Society of Hypertension. Madrid, Spain, June 19, 1992.

PMID- 7508052
TI  - The renin-angiotensin system and arterial wall behavior.
AB  - To assess the behavior of the arterial wall in hypertensive patients, we
      developed a noninvasive ultrasonic device. Simultaneous recordings of internal
      diameter and blood pressure over the whole cardiac cycle are used to establish
      compliance-pressure curves. Blood pressure, which is a co-determinant of
      compliance, is thus taken into account. This method allows one to compare
      arteries from patients with different blood pressures. Arterial compliance and
      distensibility were first investigated in healthy young volunteers administered
      either lisinopril (20 mg), atenolol (100 mg) or nitrendipine (20 mg) once a day.
      After 8 days of treatment, only lisinopril was found to increase arterial
      compliance. Subsequently, we compared arterial diameter- and distensibility
      pressure curves from newly diagnosed and untreated hypertensive patients with
      those of matched normotensive control patients. Diameter-pressure curves did not
      differ significantly between the groups and distensibility was not reduced.
      Similar findings were later obtained in an animal model, when mechanical
      properties of carotid arteries were compared between spontaneously hypertensive
      rats and normotensive counterparts (Wistar-Kyoto rats). These results, although
      interesting by providing noninvasive information on the elastic response of the
      wall, call for further development of the technique to be able to measure
      arterial wall thickness. Stress-strain relationship could ultimately be
      established to thoroughly characterize physical properties of blood vessel walls.

PMID- 7508054
TI  - The role of low-dose diuretics in essential hypertension.
AB  - Diuretics have been used to treat hypertension since 1958. The doses used were
      relatively high. Dose-dependent side effects and the increasing availability of
      other drugs such as beta- and alpha-blockers, calcium-entry blockers, and
      angiotensin-converting enzyme (ACE) inhibitors, with equal antihypertensive
      efficacy but additional effects in cardiovascular diseases, led to a decrease in
      diuretic use. In controlled trials, little or no protection against coronary
      artery disease (CAD) was discussed as being due to the diuretics' side effects.
      The main side effects are hypokalemia, hyperglycemia, and hyperlipidemia.
      Hypokalemia occurs most often (up to 30%) in thiazide-treated hypertensive
      patients, and may cause arrhythmias in patients with CAD. This side effect is
      clearly dose-dependent and may be avoided by comedication with antikaliuretics.
      Glucose intolerance may develop in about 3% of diuretic-treated men and is
      reversible after discontinuation of the diuretic. This side effect is
      functionally correlated with hypokalemia and therefore is not seen when patients
      are given a comedication (for example, spironolactone prevents hypokalemia).
      Hypercholesterolemia was first reported in 1964 during long-term diuretic
      treatment. During the first 12 weeks of treatment, low-density lipoprotein (LDL)
      cholesterol increased 5-15% in men and postmenopausal women. After 1 year of
      therapy, the levels decreased to pretreatment values. However, in placebo
      controlled trials, the placebo groups exhibited cholesterol levels falling below
      the diuretic group. Although the mechanisms and the clinical implications of
      these side effects are not completely understood, the perception grew that
      diuretics per se may have been at least partially responsible for the lack of
      protection against CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508055
TI  - Indapamide reduces hypertensive left ventricular hypertrophy: an international
      multicenter study.
AB  - The effect of 6 months of treatment with indapamide (IND, 2.5 mg/day) on
      regression of left ventricular hypertrophy (LVH), an independent predictor of
      poor prognosis in hypertension, was compared by echocardiography to that of
      nifedipine (NFD, 40 mg/day), enalapril (ENL, 20 mg/day), atenolol (ATL, 100
      mg/day), and hydrochlorothiazide (HCTZ, 25 mg/day) in four parallel double-blind
      studies in 151 hypertensive patients with a diastolic blood pressure between 95
      and 120 mm Hg and a raised left ventricular mass index (LVMI) (mg/m2) (Devereux).
      Patients were randomized to IND or comparator following a 2-week washout (1 month
      in the IND vs. ATL study). Respective baseline and 6-month LVMI values (mg/m2)
      were: IND (n = 20) vs. HCTZ (n = 20): 151.4 +/- 6.3 and 125.70 +/- 4.6 (p <
      0.001) vs. 141.3 +/- 6.6 and 135.6 +/- 8.3 (p = N.S.); IND (n = 22) vs NFD (n =
      19): 144.1 +/- 5.3 and 125.1 +/- 4.3 (p < 0.001) vs. 170.4 +/- 6.6 and 148.2 +/-
      6.2 (p < 0.001); IND (n = 9) vs. ENL (n = 9): 155.1 +/- 6.3 and 143.4 +/- 5.2 (p
      < 0.001) vs. 142.0 +/- 6.7 and 130.0 +/- 5.9 (p < 0.001); IND (n = 17) vs. ATL (n
      = 12): 146.2 +/- 5.1 and 130.8 +/- 6.5 (p < 0.001) vs. 156.7 +/- 8.4 and 142.9 +/
      10.3 (p < 0.01). All drugs significantly reduced diastolic blood pressure, and
      all except HCTZ induced a significant and similar reduction in left ventricular
      mass.

PMID- 7508056
TI  - Reactivity and sensitivity of the mesenteric artery in adult spontaneously
      hypertensive rats after chronic treatment with indapamide.
AB  - The effects of chronic treatment with indapamide (3 mg/kg/day) on the structure
      and function of the mesenteric artery were studied in two groups of spontaneously
      hypertensive rats (SHRs) using an experimental model of in situ localized
      mesenteric artery. Indapamide (n = 12) or placebo (n = 12) were given to 8-week
      old rats for 4 weeks. After anesthesia and laparotomy, a segment of mesenteric
      artery (external diameter, 300-400 microns) was exposed for video-microscopic
      measurements. The diameter-pressure relationships were established under active
      conditions (phenylephrine, 10(-6) M) and passive conditions (potassium cyanide,
      KCN) for transmural pressure ranging from atmospheric pressure to 200 mm Hg.
      These studied arterial segments were then fixed and their wall cross-sectional
      areas (CSA) measured in transverse sections. Active wall stress and tension were
      defined as the differences in wall stresses and wall tensions calculated for
      active and passive conditions. Systolic arterial pressure and mesenteric CSA were
      decreased in treated rats (197 +/- 15 mm Hg vs. 211 +/- 12 mm Hg, p < 0.05;
      16,230 +/- 1048 microns2 vs. 19,033 +/- 1082 microns2, p < 0.05). In both groups,
      mesenteric diameters were smaller under active than under passive conditions
      without significant differences in treated vs. untreated group under active
      conditions. The active wall tension was lower in treated (0.4 +/- 0.19 N/m) than
      in untreated rats (1.19 +/- 0.62 N/m, p < 0.05). However, there were no
      differences in active wall stress in both groups (103 +/- 47 kPa and 134 +/- 30
      kPa).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508057
TI  - The coronary circulation in cardiac hypertrophy.
AB  - Left ventricular hypertrophy is a common and important risk factor for cardiac
      mortality and morbidity. Cardiac hypertrophy adversely affects coronary perfusion
      because hypertension, its most frequent cause, is a major risk factor for
      coronary disease, and because cardiac hypertrophy may be associated with
      myocardial ischemia even in the absence of atheromatous coronary disease due to
      disturbances in coronary physiology. Several studies have demonstrated impairment
      of coronary reserve in human and experimental cardiac hypertrophy. Normal
      autoregulation of coronary flow may be disturbed in cardiac hypertrophy for many
      reasons, including (a) increased perfusion pressure in hypertension, (b)
      increased diastolic and systolic left ventricular pressures, in addition to
      disturbed coronary physiology. Studies undertake in the presence of maximal
      coronary vasodilatation indicate an increased minimal coronary vascular
      resistance in hypertrophied hearts. Because such measurements were determined in
      the presence of maximal coronary vasodilation, they are likely to indicate a
      reduced arteriolar lumenal cross-sectional area per unit mass of tissue. Studies
      of cardiac and coronary morphology support an imbalance in myocardial and
      coronary growth in cardiac hypertrophy, but further evidence is needed to confirm
      this. Myocardial contraction impairs coronary flow, and available evidence
      suggests that this systolic impairment may be greater in hypertrophied
      myocardium, and that this may be an additional factor in limiting coronary flow
      in hypertrophy. A further important feature of impaired coronary reserve in
      cardiac hypertrophy is its distribution. Studies using radiolabeled microspheres
      indicate that coronary reserve is reduced in endocardial regions to a much
      greater extent than epicardial regions. Previously, treatment of conditions such
      as hypertension, which are commonly associated with hypertrophy, have
      concentrated on correction of the main defect. It is important to bear in mind,
      however, that such treatments may have direct and indirect effects on the
      coronary circulation, which may have an important bearing on preserving
      myocardial function. An important aspect of future research will be to determine
      the effects of treatment on coronary perfusion.

PMID- 7508059
TI  - Effect of indapamide on cyclic adenosine 3',5'-monophosphate signal transduction
      system in isolated adult rat cardiomyocytes from normal myocardium and cardiac
      hypertrophy.
AB  - The objective of this study was to examine the effect of indapamide on cAMP
      generation in cardiomyocytes. Viable ventricular myocytes were isolated from
      adult rat hearts which included normal hearts from Wistar rats and hypertrophic
      hearts from Dahl S rats. cAMP content was measured by competitive binding assay.
      In normal heart, indapamide did not alter cAMP concentration; however, indapamide
      pretreatment markedly accentuated forskolin-stimulated cAMP production. In
      contrast to the response with forskolin, indapamide did not alter isoproterenol
      stimulated cAMP generation, suggesting an interaction of indapamide with adenyl
      cyclase rather than through the guanine stimulatory pathway affected by beta
      adrenergic stimulation by isoproterenol. Male inbred Dahl SS/Jr fed a diet
      supplemented with an additional 6% NaCl from the age of 3 weeks were randomly
      allocated to receive either indapamide 2 mg/kg s.c. per day or the diluent
      (ethanol/sterile water) in the same volume. Indapamide or diluent injections were
      begun 1 week after commencing the high-salt diet. Cardiac hypertrophy is known to
      be associated with reductions in cellular cAMP. Indapamide-treated animals had
      significantly greater myocardial cAMP concentrations than control animals.
      Hypertrophic Dahl S myocytes from untreated animals were less responsive to
      forskolin compared to myocytes from animals that had been treated with
      indapamide. Angiotensin II (Ang)-receptor stimulation with Ang II and muscarinic
      receptor stimulation with carbachol, accentuate cAMP stimulation in cardiac
      hypertrophy, whereas the reverse or inhibition was noted in normal myocardium. In
      cardiomyocytes from rats that had been treated with indapamide, the usual
      inhibitory effects of Ang II and carbachol were noted.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508058
TI  - Comparative effects of indapamide and hydrochlorothiazide on cardiac hypertrophy
      and vascular smooth-muscle phenotype in the stroke-prone, spontaneously
      hypertensive rat.
AB  - The effects of two diuretics, indapamide (3 mg/kg/day) and hydrochlorothiazide
      (20 mg/kg/day), were analyzed over a 44-day period on the cardiovascular
      hypertrophy of stroke-prone spontaneously hypertensive rats (SHR-SP). Untreated
      SHR-SP developed severe hypertension and cardiac hypertrophy when compared to
      normotensive Wistar-Kyoto (WKY) rats after 8 weeks on 1% sodium chloride. In
      diuretic-treated animals, systolic blood pressure was moderately decreased by the
      end of the treatment when compared with untreated SHR-SP (-13 and -18%,
      respectively, p < or = 0.05). Morphometric analysis of myocyte cross-sectional
      areas evidenced that indapamide was the most effective in preventing myocyte
      hypertrophy (-33%, p < or = 0.0001). Small coronary artery wall thickness was
      efficiently prevented in the two treated groups, but medial hypertrophy was
      prevented by hydrochlorothiazide only. Among markers of smooth-muscle cell
      phenotype (contractile or extracellular matrix proteins) EIIIA-fibronectin (FN),
      one FN cellular isoform, was shown to be the most sensitive marker by an
      immunohistochemical technic. Medial expression of EIIIA-FN, which was
      characteristic of SHR-SP coronary arteries, was prevented by the two treatments.
      The two diuretic treatments, despite similar effects on blood pressure and smooth
      muscle phenotype, prevent SHR-SP cardiovascular hypertrophy with a drug-specific
      efficiency.

PMID- 7508062
TI  - Study of antiatherogenic properties of indapamide in a pharmacologic model.
AB  - A localized atheromatous plaque was induced in rabbits after transmural
      electrical stimulation of the carotid and a cholesterol-rich diet (1.33%
      cholesterol) for 4 weeks. This model was used to investigate the
      antiatherogenicity of indapamide. The treatment given per os started 14 days
      before the stimulation period. Animals were divided into six groups: group 1
      (control) received gelatin 2%, group 2 received hydrochlorothiazide at 20
      mg/kg/day, group 3 was treated with flunarizine at 25 mg/kg/day, and groups 4, 5,
      and 6 received indapamide at 0.3, 1, and 3 mg/kg/day, respectively. During the
      experimental period, all rabbits showed similar weight gain, regardless of the
      treatment. Image analysis showed an antiatherogenic effect for indapamide (0.3
      mg/kg/day) characterized by a reduction in the number of cell layers (NCL; 10.5
      +/- 1.8 vs. 18.0 +/- 2.9; p < 0.05) and in the intima/media area ratio (I/M; 17.5
      +/- 4.5 vs. 42.7 +/- 7.0%; p < 0.01). Indapamide appeared to be more active than
      the reference drug flunarizine (NCL = 14.2 +/- 2.5, N.S.; I/M = 24.5 +/- 4.3, p <
      0.05). The maximum effect occurred at the lowest dose tested (0.3 mg/kg/day). The
      reason for the loss of antiatherogenic activity of indapamide at higher doses is
      discussed. Hydrochlorothiazide did not show any effect on the formation of the
      atheromatous plaque.

PMID- 7508061
TI  - Ultrastructural basis of the free-radical scavenging effect of indapamide in
      experimental myocardial ischemia and reperfusion.
AB  - Reperfusion of acutely ischemic cardiac tissue is associated with several
      characteristic pathophysiological changes that are generally referred to as
      "reperfusion injury." It has been hypothesized that some of these changes are
      mediated by oxygen-derived free radicals. Indapamide, a nonthiazide diuretic, has
      been shown to exert free-radical scavenging properties comparable to that of
      alpha-tocopherol. The purpose of the present work was to investigate whether
      indapamide (IDP) may limit ultrastructural signs of reperfusion injury in an
      experimental model of myocardial ischemia and reperfusion in isolated rat hearts.
      Rats received a chronic oral administration of IDP (7 days at 3 mg/kg body
      weight/day) before excision of the heart. IDP was also added to the perfusion
      fluid at a final concentration of 10(-4) M. Isolated hearts were perfused under
      control conditions for 20 min and then submitted to 15 min of global no-flow
      ischemia, before being reperfused for 15 min. Hearts were fixed by glutaraldehyde
      perfusion fixation and left ventricular ultrastructure was studied on ultra-thin
      sections by electron microscopy. Micrographs were taken following a random
      procedure to obtain a representative overview of the whole section. In the
      untreated group, marked ultrastructural alterations were observed including
      contraction bands, disrupted membranes, and swollen mitochondria. In the
      indapamide-treated group, the degree of morphological injury was significantly
      lessened. It is concluded that indapamide protects the ultrastructure of
      ventricular myocytes against reperfusion injury. This effect might be related to
      the oxygen free-radical scavenging property of the drug.

PMID- 7508060
TI  - Oxygen radical scavengers and renal protection by indapamide diuretic in salt
      induced hypertension of Dahl strain rats.
AB  - In addition to the hemodynamic components, the roles of various humoral factors
      have been emphasized in the progression of vascular and renal injury in
      hypertension. Radical scavenging properties have attracted much attention in this
      field. This article discusses the implication of antioxidant properties of the
      antihypertensive diuretic indapamide on renal injury in Dahl salt-sensitive (Dahl
      S) rats. Hydroxyl radicals, oxygen radicals toxic to cellular membranes, are
      eradicated by indapamide in different assay systems, e.g., reduction of alpha
      alpha-diphenyl-beta-picrylhydrazyl, rat brain homogenate, or xanthine-xanthine
      oxidase systems. Such antioxidant effects of indapamide are primarily due to
      inhibition of lipid peroxidation induced by hydroxyl radicals, and this mechanism
      may stimulate prostacyclin generation through activation of prostacyclin
      synthase. In fact, the antioxidant properties of indapamide are well expressed in
      vivo as well; indapamide treatment reduced oxygen radicals in the kidney of Dahl
      S rats with hypertension. This was accompanied by a functional improvement of the
      kidney; decreases in urinary protein and n-acetylglucosaminidase excretion and an
      increase in glomerular filtration rate were observed. In addition, indapamide
      morphologically ameliorated the renal injury, and decreased glomerular sclerosis
      score, arterial injury, and renal tubular injury. Trichloromethiazide reduces
      blood pressure similar to that produced by indapamide. However,
      trichloromethiazide did not lead to reduction of oxygen radicals in the kidney,
      and did not improve the functional disturbance or morphological injury seen in
      Dahl S rats. These results indicate that indapamide has antioxidant properties,
      and in addition to blood pressure reduction, such radical scavenging effects may
      contribute to its beneficial effects on renal function in vivo.

PMID- 7508063
TI  - Indapamide inhibits human platelet aggregation in vitro: comparison with
      hydrochlorothiazide.
AB  - Among antihypertensive drugs with diuretic properties, indapamide was shown to
      inhibit platelet growth factors production in diabetic hypertensive patients,
      suggesting an antiplatelet activity. The present study aimed to demonstrate the
      antiaggregating properties of indapamide. The effect of indapamide on platelet
      function was compared in vitro to that of hydrochlorothiazide. Indapamide (100
      microM) inhibited the second wave of adenosine diphosphate-induced aggregation
      and inhibited collagen-induced aggregation of platelet rich plasma by 50%. Using
      isolated platelets, indapamide also inhibited aggregation induced by low doses of
      thrombin (70% inhibition with 0.035 U/ml). This inhibition was dose-dependent and
      was still observed in presence of high thrombin concentrations, although the
      inhibition was moderate. Inhibitory effect of indapamide was more pronounced on
      the release reaction. Indapamide inhibited the thrombin-induced release of
      serotonin from dense granules by up to 80%. Hydrochlorothiazide at the same
      concentrations had no effect on platelet aggregation, and the inhibitory effect
      on the secretion was inconsistent and never exceeded 30%. By contrast, when the
      aggregation inducer was arachidonic acid, indapamide had no effect either on
      aggregation or on thromboxane formation, indicating that it was not acting on
      arachidonic catabolism. Calcium mobilization evoked by thrombin stimulation and
      measured with the fluorescent dye Indo 1 was also reduced in presence of
      indapamide by 30%. Myosin light chain and pleckstrin phosphorylation induced by
      thrombin were also reduced. These results demonstrate that indapamide inhibits
      platelet responses by inhibiting calcium mobilization. The anti-aggregating
      properties of indapamide could contribute to normalize the hyperresponsiveness of
      platelets from hypertensive patients.

PMID- 7508064
TI  - Platelets, growth factors, and vascular smooth-muscle cells in hypertension and
      diabetes.
AB  - Inappropriate vascular smooth-muscle cell (VSMC) growth is the hallmark of
      vascular pathology in essential hypertension and diabetic macroangiopathy,
      whereas platelets constitute an important regulator of vessel wall homeostasis
      because of their content of various growth factors. Numerous abnormalities exist
      in platelet functions in diabetes and hypertension, such as enhanced activity and
      altered adhesion and aggregation. Increased thromboxane (TX2) production is
      characteristic of diabetes, and an elevation of intracellular free Ca2+ is found
      in platelets of hypertensive patients. By studying the growth patterns of VSMC
      from spontaneously hypertensive rats (SHRs) vs. those obtained from their
      normotensive counterparts, Wistar-Kyoto (WKY) rats, we have demonstrated that
      VSMC from SHRs exhibited a higher specific growth rate, abnormal contact
      inhibition, and accelerated entry into the S phase of the cell cycle. Moreover,
      they were hyperresponsive to many growth factors such as calf serum, epidermal
      growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth
      factor beta 1 (TGF beta 1), and insulin. Additive effects were observed for EGF
      and PDGF or EGF and insulin. These intrinsic growth anomalies in cells of
      hypertensive origin persist in culture indicating their putative primary role in
      the pathogenesis of hypertension. Endogenous TGF beta 1 revealed an augmented
      expression of its message levels in SHR VSMC, the difference in mRNA between both
      strains being more pronounced at high cell density. Further, TGF beta 1 protein
      synthesis and secretion in VSMC culture were confirmed by immunoprecipitation of
      de novo labeled TGF beta 1. At high cell density, which most likely represents
      the physiological state of VSMC, plasmin, an activator of TGF beta 1,
      significantly stimulated DNA synthesis of VSMC in both strains. The reverse
      effect was obtained at low cell density. Yet, the fold stimulation was higher in
      WKY rats, suggesting that TGF beta 1 may be partially activated in SHR VSMC. This
      is supported by the inhibition of baseline DNA synthesis by TGF beta 1
      neutralizing antibody in VSMC of hypertensive origin and not of normotensive
      controls. TGF beta 1 antisense oligodeoxynucleotide (ODN) nearly normalized the
      increased proliferation of SHR VSMC in culture. On the other hand, growth
      promoting activity (GPA) in platelets of either diabetic or hypertensive patients
      was higher than in platelets of healthy controls and was found to be normalized
      by intensive insulin therapy in insulin-dependent diabetic patients. In
      hypertensive patients, however, hydrochlorothiazide (HCTZ)--even in low doses (25
      mg/day)--enhanced the GPA in platelets, whereas other antihypertensive agents
      such as indapamide, atenolol, and captopril, had neutral effects.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7508065
TI  - Regression of microalbuminuria: results of a controlled study, indapamide versus
      captopril.
AB  - Our aim was to assess the effect of blood pressure treatment on albumin excretion
      rate (AER) in diabetic patients using two antihypertensive agents with different
      modes of action: indapamide and captopril. Patients with persistent
      microalbuminuria on two occasions (AER 20-200 micrograms/min) entered a
      randomized crossover study of 12 weeks of therapy with a constant dose of either
      indapamide 2.5 mg daily or captopril 12.5 mg three times daily, with a 4-week
      washout between therapy periods. Blood pressure was measured using a random-zero
      sphygmomanometer and AER by radioimmunoassay on a timed urine collection. Results
      (mean +/- standard deviation) were analyzed by repeated measures of analysis of
      variance after log transformation of AER data. Twelve patients [nine men; mean
      age 58 +/- 7.5 years (range 49-73 years), all with non-insulin-dependent diabetes
      mellitus (NIDDM)] were studied. Both blood pressure [initial mean systolic 144 +/
      14 mm Hg (range 124-166)/initial mean diastolic 85 +/- 6 mm Hg (range 75-96)]
      and AER [initial 92 +/- 36 micrograms/min (range 36-161)] were significantly
      reduced below basal levels (at the 0.05 level) at all study intervals by both
      antihypertensive agents. The results show the importance of blood pressure and
      its treatment on AER in patients with NIDDM. In this study, indapamide was as
      effective as an angiotensin-converting enzyme inhibitor in reducing both blood
      pressure and microalbuminuria.

PMID- 7508066
TI  - Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing
      calcium stone recurrences.
AB  - We examined the biochemical changes and the efficacy of indapamide in the
      prevention of calcium stone recurrences. Seventy-five patients with calcium
      nephrolithiasis and hypercalciuria were randomly assigned to three different
      therapies: diet and fluid (group A), diet and fluid plus indapamide 2.5 mg/day
      (group B), and diet and fluid plus indapamide 2.5 mg/day plus allopurinol 300
      mg/day (group C). Before treatment and after 6, 12, 24, and 36 months of therapy,
      we evaluated blood pressure, serum and urine risk parameters (including relative
      supersaturations of calcium oxalate, calcium phosphate and uric acid), stone
      rate, and the proportion of calculi-free patients. During the 3 years of
      treatment, urinary calcium greatly decreased in groups B and C, dropping to 50%
      of the pretreatment values; urinary oxalate also significantly declined in group
      B (-24%) and group C (-27%). Relative supersaturations of calcium oxalate and
      calcium phosphate decreased to the same extent in groups B and C (about one-half
      of the pretreatment value), and relative supersaturation of uric acid was
      particularly reduced in group C (-65% of the pretreatment value). The stone rate
      improved in all three groups (p < 0.005), but using actuarial analysis in the
      evaluation of calculi-free patients, indapamide, and indapamide plus allopurinol
      groups were found to have a significantly more favorable effect than diet and
      fluid treatment (p < 0.02), without any difference between the two drug groups.
      Because indapamide has fewer side effects than thiazide diuretics, we conclude
      that indapamide could be an interesting alternative to thiazides in the
      prevention of calcium stones in hypercalciuric patients.

PMID- 7508067
TI  - Effects of indapamide on vascular reactivity in hypercholesterolemic rabbits.
AB  - We tested the effects of indapamide (IND), an antihypertensive drug, on the
      contractile responsiveness of femoral and mesenteric arteries isolated from
      rabbits fed with a 1% cholesterol diet for 16 weeks. IND (0.1, 0.3, 1 mg/kg/day)
      was given to the experimental groups of rabbits, whereas control groups received
      either a standard or a cholesterol-enriched diet. Contractions caused by
      submaximal doses of norepinephrine (NE) or high-K were significantly decreased in
      the femoral artery of untreated hypercholesterolemic rabbits. The responses to
      NE(10(-6) M) or to KCI (80 mM) expressed as a percentage of the control group
      (standard diet) contractions were 77.0 +/- 3.3% and 55.0 +/- 4.2%, respectively.
      Vascular reactivity was preserved in the rabbits fed the atherogenic diet
      supplemented with IND in a concentration-dependent manner. In addition, in the
      experimental groups dose-response curves to NE (10(-8) to 10(-4) M) and to KCI
      (20-120 mM) were shifted upward and to the left with respect to the control
      hypercholesterolemic group. In the mesenteric artery (fifth branch) NE- and K
      induced contractions were not significantly altered by hypercholesterolemia. We
      conclude that IND treatment may prevent femoral arteries from a loss of
      reactivity probably by reducing the severity of atherosclerosis.

PMID- 7508068
TI  - Carbohydrate metabolism in hypertension: influence of treatment.
AB  - Epidemiologic studies suggest a close association between hypertension, obesity,
      and diabetes. It has been demonstrated that essential hypertension, per se, is an
      insulin-resistant state. However, the pathogenesis of the association between
      insulin resistance and hypertension is poorly understood. Elevated plasma insulin
      levels may contribute to the development of hypertension through renal sodium
      reabsorption, the sympathetic nervous system, the transmembranous cation
      transport, the renin-angiotensin system, the cardiovascular reactivity, and the
      atrial natriuretic peptide. Diuretics, beta-blockers, calcium antagonists,
      angiotensin-converting enzyme (ACE) inhibitors, and alpha 1-antagonists are first
      choice drugs in the management of hypertension. Diuretics, except indapamide,
      impair insulin sensitivity and glucose tolerance. The same negative effects,
      exerted by beta-blockers, are reduced employing those with selective activity.
      With few exceptions, calcium antagonists have no adverse influence on
      carbohydrate metabolism. ACE inhibitors and alpha 1-antagonists do not influence
      or even improve glucose metabolism.

PMID- 7508069
TI  - Serum lipoproteins during treatment with antihypertensive drugs.
AB  - Several drugs used for antihypertensive therapy may modify the lipoprotein
      metabolism. Thiazides in high dosage and loop diuretics can increase serum low
      density lipoprotein (LDL) cholesterol and/or very-LDL cholesterol and the total
      cholesterol/high-density lipoprotein (HDL) cholesterol ratio, while HDL
      cholesterol is largely unchanged; triglycerides (Tg) are also often elevated.
      Premenopausal women may be protected from this side effect. Whether diuretic
      induced dyslipidemia is dose-dependent and low thiazide doses (i.e.,
      hydrochlorothiazide < or = 12.5 mg daily) are interacting less, awaits
      clarification. beta-Blockers without intrinsic sympathomimetic activity increase
      serum triglycerides and tend to lower the potentially antiatherogenic HDL
      cholesterol. The diuretic-antihypertensive agent indapamide, given at a dose of
      2.5 mg/day, is neutral with regard to serum lipoprotein and glucose metabolism.
      The potassium-sparing diuretic spironolactone, conventional sympatholytic agents,
      calcium-channel blockers, and probably the serotonin2-receptor antagonist
      ketanserin, exert no relevant effects on the lipoprotein profile. Angiotensin
      converting enzyme inhibitors may slightly decrease serum triglycerides. alpha 1
      Receptor blockers slightly decrease LDL cholesterol and Tg and increase HDL
      cholesterol. Drug-induced development or aggravation of dyslipidemia represents a
      potentially adverse influence. In the hypertensive population, effective blood
      pressure control with traditional drug therapy based on thiazide-type diuretics
      in high dosage led to a distinct decrease in cerebrovascular morbidity and
      mortality, but failed to satisfactorily reduce coronary complications. The
      prognostic relevance of drug-induced changes in serum lipoproteins, carbohydrate
      metabolism and other risk factors or correlates awaits further
      clarification.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508070
TI  - Aprotinin for coronary bypass operations: efficacy, safety, and influence on
      early saphenous vein graft patency. A multicenter, randomized, double-blind,
      placebo-controlled study.
AB  - The purpose of this study was to evaluate the efficacy and safety of aprotinin in
      a U.S. population of patients undergoing coronary artery bypass grafting. Early
      vein graft patency rates were assessed by ultrafast computed tomography. A total
      of 216 patients at five centers were randomized to receive either high-dose
      aprotinin or placebo during the operation; 151 patients underwent primary
      operation, and 65 underwent repeat procedures. Total blood product exposures in
      the primary group were 2.2 per patient receiving aprotinin as compared with 5.7
      per patient receiving placebo (p = 0.010). The repeat group had 0.3 exposures per
      patient receiving aprotinin as compared with 10.7 per patient receiving placebo
      (p = < 0.001). Consistent reductions in the percent of patients requiring donor
      red blood cells and in the number of units of platelets, fresh frozen plasma, and
      cryoprecipitate required were associated with the use of aprotinin in both
      primary and repeat groups. Mortality was 5.6% in the aprotinin group and 3.7% in
      the placebo group (p = 0.517). In the primary group, clinical diagnoses of
      myocardial infarction were made in 8.9% of patients receiving aprotinin as
      compared with 5.6% of the patients receiving placebo (p = 0.435). In the repeat
      group, infarctions occurred in 10.3% of patients receiving aprotinin and 8.3% of
      patients receiving placebo (p = 1.000). Secondary analysis of electrocardiograms
      and available enzyme data showed no significant difference in infarction rates
      between the treatment groups. There was no difference in clinically significant
      renal dysfunction. The early vein graft patency rates were 92.0% in the aprotinin
      group and 95.1% in the placebo group (p = 0.248). In this study, aprotinin was
      effective in reducing bleeding and blood product transfusion rates, and its use
      was not associated with an increase in complications. An adverse effect on early
      vein graft patency rates was not demonstrated, but the number of grafts assessed
      was insufficient for absolute conclusions in this regard.

PMID- 7508071
TI  - Aprotinin significantly decreases bleeding and transfusion requirements in
      patients receiving aspirin and undergoing cardiac operations.
AB  - BACKGROUND: Patients with heart disease are frequently maintained on a regimen of
      aspirin because of its ability to decrease thrombotic complications and reduce
      the prevalence of unstable angina and myocardial infarction. Aspirin-induced
      platelet acetylation also increases bleeding caused by impairment of platelet
      function during cardiac surgery. METHODS: Between October 1990 and November 1991
      this double-blind, randomized, placebo-controlled, parallel group interventional
      study examined the efficacy of high-dose aprotinin administration (up to 7
      million KIU) to decrease blood loss and transfusion requirements in patients
      receiving aspirin within 48 hours of undergoing coronary bypass or valvular heart
      operations. Primary outcome measures in this study were total volume of blood
      loss (intraoperative blood loss plus postoperative chest tube drainage) and
      volume of transfusion during hospitalization. RESULTS: Patients treated with
      aprotinin (n = 29) had significantly lower total blood loss (1409 +/- 232 ml
      versus 2765 +/- 248 ml; p = 0.0002), intraoperative blood loss (503 +/- 53 ml
      versus 1055 +/- 199 ml; p = 0.0001), postoperative blood loss (906 +/- 204 ml
      versus 1710 +/- 202 ml; p = 0.0074), and prevalence of transfusion (59% versus
      88% of patients; p = 0.016) than the placebo group (n = 25). The prevalence of
      complications including myocardial infarction was similar in the two groups.
      CONCLUSIONS: High-dose aprotinin significantly reduces blood loss and red blood
      cell transfusions in patients receiving aspirin who undergo cardiac operations.

PMID- 7508072
TI  - Management of intra-arterial injection injury with iloprost.

PMID- 7508073
TI  - [Critical review of drugs in 1991].

PMID- 7508074
TI  - Alzheimer's amyloid precursor protein mRNA without exon 15 is ubiquitously
      expressed except in the rat central nervous system.
AB  - The expression of L-beta A4 amyloid precursor protein (L-APP) mRNA, which is a
      splicing product excluding exon 15 of the APP gene, was investigated in various
      tissues of adult rats by a polymerase chain reaction analysis of reverse
      transcribed RNA (RT-PCR). L-APP mRNA was ubiquitously expressed in all the
      examined tissues including the liver, kidney, heart, skeletal muscle, spleen,
      thymus, adrenal, stomach, submandibular gland, testis and ovary, except for the
      central nervous system (CNS) tissues such as the brain and spinal cord. The DNA
      sequence analysis of the RT-PCR products from adult rat liver showed an L-APP
      cDNA form, in which exon 14 was spliced from exon 14 to exon 16, and exon 15 of
      the APP gene was excluded. In addition, regarding as the brain and liver, L-APP
      mRNA expression was examined during the development of the embryonic stage. In
      the brain, no L-APP mRNA expression was detected even in the embryonic stage,
      whereas L-APP mRNA expression of the liver was still found in the embryonic
      stage. These results suggest that the splicing event excluding exon 15, which is
      exactly adjacent to exon 16 and exon 17 encoding the beta A4 protein, would
      probably occur very rarely in the CNS and that the splicing of L-APP might
      already be regulated in the embryonic stage.

PMID- 7508075
TI  - Terazosin for benign prostatic hyperplasia.

PMID- 7508077
TI  - [Treatment of condyloma acuminatum in children. Comment on 20 cases observed in
      the past 10 years].
AB  - The treatment of condyloma acuminatum in children is still controversial. The
      ideal treatment should take into account the efficacy of eradicating infection,
      but also the child's tolerance of treatment and its ease of use. Twenty cases
      observed by the authors over the course of the past 10 years are described. A
      treatment protocol is drawn up on the basis of a review of the latest reports on
      this topic and the availability of new products.

PMID- 7508081
TI  - Epitope complementarity and idiotypic interactions: a study of idiotypic-like
      interactions between anti-cytidine and anti-guanosine A/J mouse monoclonal
      antibodies--II. Analysis of the gene repertoire used to encode the variable
      regions of these antibodies.

PMID- 7508080
TI  - Epitope complementarity and idiotypic interactions: a study of idiotypic-like
      interactions between anti-cytidine and anti-guanosine A/J mouse monoclonal
      antibodies--I. Characterization of these interactions.
AB  - Idiotypic-like interactions between mAbs directed against cytidine (Cyd) or
      guanosine (Guo) nucleosides were characterized. These mAbs, Cyd-1 (IgG2b, kappa),
      Guo-1 (IgG1, kappa) and Guo-2 (IgG1, kappa) were derived from splenocytes of A/J
      mice immunized with Cyd-KLH or Guo-KLH and recognized the nucleoside base
      moieties involved in hydrogen bonding. The interactions between Guo-1 or Guo-2
      and Cyd-1 involved cross-reactive or distinct-but-neighboring paratope-associated
      idiotopes. These interactions were characterized by KD values of 4.6 x 10(-6) and
      1.8 x 10(-6)M, respectively. The three anti-nucleoside mAbs exhibited Ab2 beta
      properties and manifested epibody (Ab2 epsilon) activity towards ssDNA. We
      compared these idiotypic-like reactivities with the anti-idiotypic activity of an
      intentionally induced IgG1, kappa anti-idiotype mAb prepared with splenocytes
      from A/J mice immunized with Cyd-1. This Ab2 antibody which bound to Cyd-1 with a
      KD of 1.1 x 10(-9) M, manifested an Ab2 gamma activity, i.e. it recognized a
      paratope-associated idiotope on Cyd-1 without exhibiting Ab2 beta properties. In
      addition, the anti-(Cyd-1) completely inhibited (Cyd-1)-(Guo-1) and (Cyd-1)-(Guo
      2) interactions.

PMID- 7508079
TI  - An apparently common mechanism of generating antibody diversity: length variation
      of the VL-JL junction.
AB  - The joining of various V, (D) and J gene segments during DNA rearrangement of the
      antigen receptor genes is one of the principle mechanisms responsible for the
      generation of antibody diversity. In the absence of N-segment variation, the
      structures of the coding joints formed during light chain rearrangement are
      thought to be less complex than their heavy chain counterparts. Consequently, the
      joining of the VL and JL gene segments during recombination account for all of
      the junctional diversity seen within the third complementarity determining region
      (CDR3). We generated kappa light chain transcripts from human fetal liver and
      peripheral blood lymphocytes and found that approximately one third exhibit a
      variation in the length of CDR3-independent of the JK gene segment utilized.
      Nucleotide sequence analysis reveals that many of the nucleotides at the VK-JK
      joint resulting in length variation of CDR3 are directly encoded by the germline
      VK and JK gene segments used in these transcripts. However, nearly 20% of the
      transcripts contain N-segment additions consistent with TdT-like activity. These
      observations suggest that TdT or an analogous enzyme must be active in a
      significant percentage of human B-lymphocytes during light chain rearrangement.
      Length variation in light chain CDR3 expands the potential repertoire and thus
      contributes an additional means of generating diversity in the antibody molecule.

PMID- 7508078
TI  - Expression of mRNA for epidermal growth factor, transforming growth factor-alpha
      and their receptor in human prostate tissue and cell lines.
AB  - Enhanced expression of the epidermal growth factor receptor (EGFR) or its
      ligands, epidermal growth factor (EGF) and transforming growth factor alpha (TGF
      alpha) can increase signalling via receptor-mediated pathways which may lead to
      excessive proliferation and cellular transformation. Such autocrine regulation of
      growth has been demonstrated for prostate cancer cell lines in culture but its
      role in prostate cancer in vivo has not been established. To assess the potential
      of such a mechanism, we have examined the pathway components in prostate
      carcinomas (CaP) in comparison with non-malignant benign prostatic hyperplasias
      (BPH). In the present study, we investigate the dosage, structure and expression
      of EGF, TGF-alpha and EGFR genes in a series of 34 human prostate samples and 3
      prostate cancer cell lines. All of the samples contained transcripts from each of
      the genes. The expression of pre-pro-TGF-alpha mRNA and pre-pro-EGF mRNA were
      significantly higher in CaP (n = 13) than BPH (n = 21) specimens (p < 0.05). The
      androgen-responsive prostatic carcinoma cell line, LNCaP, expressed high levels
      of EGF mRNA while the androgen-independent DU145 and PC-3 cell lines expressed
      high levels of TGF-alpha mRNA and EGFR mRNA. In general, overexpression of these
      mRNAs was not associated with amplification or detectable gene rearrangement;
      only DU145 cells demonstrated any alteration in these genes, with apparent
      amplification of the TGF-alpha gene. Relative to BPH, all prostate carcinomas and
      cell lines studied had elevated levels of mRNA for one or both mRNA coding for
      the ligands for EGFR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508082
TI  - Genotoxicity of kraft pulp spent liquors from different types of chlorination
      procedures.
AB  - The genotoxicity of spent liquors from kraft softwood and hardwood pulp bleaching
      processes was studied using the Ames Salmonella test and the SOS chromotest. The
      induction of micronuclei, in vivo, was assayed in bone marrow erythrocytes of B6
      mice treated with softwood first chlorination stage spent liquor. The softwood
      bleaching process used a combination of Cl2 and ClO2 at the first chlorination
      stage. During the study the amount of free chlorine at the first chlorination
      stage in the softwood bleachery was gradually decreased, although the amount of
      active chlorine remained the same. Enzymatic bleaching was also used in a
      softwood process together with chlorine (Cl2 + ClO2). The hardwood bleaching
      plant used only ClO2 at the first chlorination stage. A decrease in genotoxicity,
      corresponding to the decrease in Cl2, was observed in the Ames Salmonella assays
      of the softwood bleaching plant effluents. A similar decrease was observed in the
      SOS chromotest. The highest decrease in mutagenic activity was observed when
      enzymatic bleaching was used together with chlorine.

PMID- 7508083
TI  - Genotoxic evaluation of eugenol using the bone marrow micronucleus assay.
AB  - Eugenol, a widely used chemical in clinical dentistry, was evaluated for
      genotoxicity using the bone marrow micronucleus (Mn) assay in mice. Three doses
      (100, 400 or 600 mg/kg) were administered intraperitoneally (i.p.). The animals
      were killed 30 h post-treatment and the frequency of Mn in 1000 polychromatic
      erythrocytes (PCE) was determined. Corn oil and methyl methanesulfonate (MMS)
      were used as negative and positive controls, respectively. Only 400 and 600 mg/kg
      doses showed significant induction of Mn. We also studied the effect of eugenol
      at different recovery times (24, 30 or 48 h) with a dose of 400 mg/kg. A positive
      Mn response was seen at all three post-treatment times, but the differences
      between them were not significant. For treatment and control groups, the
      cytotoxicity was in the normal range, measured as the ratio of PCE/NCE
      (normochromatic erythrocytes).

PMID- 7508084
TI  - Genotoxicity evaluation of Rastim 30 DKV, the plant growth regulator, on five
      test systems.
AB  - The possible mutagenic activity of Rastim 30 DKV, a new plant growth regulator,
      was studied on five model test systems. It did not increase the frequency of His+
      revertants in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, TA1538 in
      the absence and the presence of S9 mix. It slightly increased rates of genetic
      changes in Saccharomyces cerevisiae, mainly convertants at the tryptophan locus.
      No clastogenic effect was observed after Vicia faba root-tip meristem treatment,
      and at the lowest concentration used its mitotic activity was significantly
      increased. No chlorophyll mutants after the treatment of two cultivars of barley
      were observed. Though no sex-linked recessive lethals were scored in Drosophila
      melanogaster males, the rates of aneuploids induced in their germ cells were
      significantly increased.

PMID- 7508085
TI  - An in vivo-in vitro replicative DNA synthesis (RDS) test using rat hepatocytes as
      an early prediction assay for nongenotoxic hepatocarcinogens screening of 22
      known positives and 25 noncarcinogens.
AB  - To evaluate the applicability of an in vivo-in vitro replicative DNA synthesis
      (RDS) test using rat hepatocytes, we conducted the RDS test with 22 nongenotoxic
      (Ames-negative) hepatocarcinogens and 25 noncarcinogens under our standardized
      conditions and judgement criteria. Compared to controls (RDS incidence of under
      1.0%), the RDS test gave positive results for 18 hepatocarcinogens (positive
      sensitivity: 82%), and negative results for 20 noncarcinogens (negative
      specificity: 80%), and thus the overall concordance was 81%. These findings
      strongly suggest that the RDS test is an extremely useful method for early
      detection of nongenotoxic hepatocarcinogens.

PMID- 7508086
TI  - Cytotoxicity and DNA damaging potency of chloramphenicol and six metabolites: a
      new evaluation in human lymphocytes and Raji cells.
AB  - Chloramphenicol (CAP) is an antibiotic which has been implicated in the etiology
      of aplastic anemia in man. This product is also used in veterinary medicine. The
      medical use of chloramphenicol has been limited to cases where the drug is
      indispensible but veterinary use may lead to the presence of residues in the meat
      of treated animals and it is essential to establish acceptable levels of intake
      of such residues in order to protect human health. CAP is metabolized into at
      least 6 metabolites: nitroso-CAP (NO-CAP), formed in the liver, 3 excretion
      products: the glucuronide (CAP-G), the CAP base (NAPD), and an alcoholic
      derivative, HAP. Dehydro-CAP (DH-CAP) and the dehydro-CAP base (NPAP) are formed
      by enterobacteria in the large bowel. The objective of the present study was to
      investigate (1) the cytotoxicity of CAP and its metabolites and (2) their ability
      to induce DNA damage in human cells. This work was performed with human
      peripheral blood lymphocytes (PBL) and with a lymphoma cell line (Raji).

PMID- 7508087
TI  - No cyclosporin-induced chromosomal aberrations in human peripheral blood
      lymphocytes in vitro.
AB  - Continuous in vitro treatment of human peripheral blood lymphocytes with
      cyclosporin A for 20 h and 44 h in the absence of metabolic activation decreased
      the mitotic index in a concentration-dependent way (MI about 35% at 50
      micrograms/ml). In the presence of 10% S9 lymphocytes were exposed to cyclosporin
      A at concentrations which formed cloudy suspension, i.e., above 100
      micrograms/ml. A 2 h treatment in the presence of metabolic activation showed a
      depression of the mitotic index at the 44 h fixation time only. Based upon
      results concerning the depression of the mitotic index, slides of the 5, 10, 25
      and 50 micrograms/ml (-S9, 20 h and 44 h continuous treatment) and 5, 150, 250
      and 300 micrograms/ml (+S9, 2 h pulse treatment) treatment groups were selected
      to be analyzed in the chromosomal aberration assay. At no concentration and at no
      fixation time did cyclosporin A increase the frequency of cells with chromosomal
      aberrations.

PMID- 7508089
TI  - The role of formaldehyde and S-chloromethylglutathione in the bacterial
      mutagenicity of methylene chloride.
AB  - Methylene chloride was less mutagenic in Salmonella typhimurium TA100/NG-11
      (glutathione-deficient) compared to TA100, indicating that glutathione is
      involved in the activation of methylene chloride to a mutagen in bacteria. In
      rodents, the pathway of methylene chloride metabolism utilizing glutathione
      produces formaldehyde via a postulated S-chloromethylglutathione conjugate
      (GSCH2Cl). Formaldehyde is known to cause DNA-protein cross-links, and GSCH2Cl
      may act as a monofunctional DNA alkylator by analogy with the glutathione
      conjugates of 1,2-dihaloalkanes. The lack of sensitivity of Salmonella TA100
      towards formaldehyde (Schmid et al., Mutagenesis, 1 (1986) No. 6, 427-431)
      suggests that GSCH2Cl is responsible for methylene chloride mutagenicity in
      Salmonella. In Escherichia coli K12 (AB1157), formaldehyde was mutagenic only in
      the wild-type, a characteristic shared with cross-linking agents, whereas 1,2
      dibromoethane (1,2-DBE) was more mutagenic in uvrA cells (AB1886). Methylene
      chloride, activated by S9 from mouse liver, was mutagenic only in wild-type
      cells, suggesting a mutagenic role for metabolically derived formaldehyde in E.
      coli. Mouse-liver S9 also enhanced the cell-killing effect of methylene chloride
      in the uvrA, and a recA/uvrA double mutant (AB2480) which is very sensitive to
      DNA damage. This pattern was consistent with formaldehyde damage. However, a
      mutagenic role in bacteria for the glutathione conjugate of methylene chloride
      cannot be ruled out by these E. coli experiments because S9 fractions did not
      increase 1,2-DBE mutagenicity, suggesting lack of cell wall penetration by this
      reactive species. Rat-liver S9 did not activate methylene chloride to a bacterial
      mutagen or enhance methylene chloride-induced cell-killing, which is consistent
      with the carcinogenicity difference between the species.

PMID- 7508088
TI  - Chromosome damage in lymphocytes of stainless steel welders related to past and
      current exposure to manual metal arc welding fumes.
AB  - Cytogenetic damage was studied in lymphocytes from 42 welders using the manual
      metal arc (MMA) method on stainless steel (SS). A detailed characterization of
      previous exposure by job interviews, and for current exposure with personal air
      sampling and biological monitoring of chromium (Cr) and nickel (Ni) in blood and
      urine, was done for 32 of these welders. A subgroup of 20 welders was studied
      before and after 1-4 months of MMA/SS welding. A matched reference group I, and a
      larger reference group II were established for comparison. A significant increase
      in chromatid breaks (1.4 vs. 0.9 and 0.8 for group I and II) and for cells with
      aberrations (2.2 vs. 1.6 in group II) was found in the welders. An even larger
      difference was found when comparing non-smoking welders with their non-smoking
      referents. No synergistic effect between smoking and MMA/SS welding fumes was
      observed for any type of aberrations. Current welding fume exposure during the
      week before sampling was not associated with increases in any type of cytogenetic
      damage. The results indicated that the increase in chromatid breaks was
      associated with cumulated welding fume exposure for more than a year, and with
      not using respirators. Exposure to MMA/SS welding fumes for up to 4 months gave a
      slight, but significant increase in chromatid breaks when using the welders as
      their own referents. However, when using matched referents in the study after
      exposure, no difference was found between these welders and their matched
      referents. No differences between the groups were observed in the DNA synthesis
      and repair-inhibited cultures or for SCE.

PMID- 7508090
TI  - Pan masala--a genotoxic menace.
AB  - Cytogenetic markers such as chromosome aberration (CA), sister-chromatid exchange
      (SCE) and micronucleated cells (MNC) were used to assess the genotoxic potential
      of dimethyl sulphoxide (DMSO) extract of pan masala with and without tobacco (PM
      T and PM). Using in vitro short-term assays, the extracts were tested in the
      presence or absence of metabolic activation. In cultures without metabolic
      activation the extracts were found to increase the frequency of all the three
      parameters tested significantly, however those with activation elicited a weak
      response, implying that pan masalas contain solvent (DMSO)-soluble direct-acting
      mutagen.

PMID- 7508091
TI  - Screening tests for chemicals.

PMID- 7508092
TI  - Pain and its treatment in outpatients with metastatic cancer.
AB  - BACKGROUND AND METHODS: Pain is often inadequately treated in patients with
      cancer. A total of 1308 outpatients with metastatic cancer from 54 treatment
      locations affiliated with the Eastern Cooperative Oncology Group rated the
      severity of their pain during the preceding week, as well as the degree of pain
      related functional impairment and the degree of relief provided by analgesic
      drugs. Their physicians attributed the pain to various factors, described its
      treatment, and estimated the impact of pain on the patients' ability to function.
      We assessed the adequacy of prescribed analgesic drugs using guidelines developed
      by the World Health Organization, studied the factors that influenced whether
      analgesia was adequate, and determined the effects of inadequate analgesia on the
      patients' perception of pain relief and functional status. RESULTS: Sixty-seven
      percent of the patients (871 of 1308) reported that they had had pain or had
      taken analgesic drugs daily during the week preceding the study, and 36 percent
      (475 of 1308) had pain severe enough to impair their ability to function. Forty
      two percent of those with pain (250 of the 597 patients for whom we had complete
      information) were not given adequate analgesic therapy. Patients seen at centers
      that treated predominantly minorities were three times more likely than those
      treated elsewhere to have inadequate pain management. A discrepancy between
      patient and physician in judging the severity of the patient's pain was
      predictive of inadequate pain management (odds ratio, 2.3). Other factors that
      predicted inadequate pain management included pain that physicians did not
      attribute to cancer (odds ratio, 1.9), better performance status (odds ratio,
      1.8), age of 70 years or older (odds ratio, 2.4), and female sex (odds ratio,
      1.5). Patients with less adequate analgesia reported less pain relief and greater
      pain-related impairment of function. CONCLUSIONS: Despite published guidelines
      for pain management, many patients with cancer have considerable pain and receive
      inadequate analgesia.

PMID- 7508093
TI  - Treatment of leukemia in relapse after bone marrow transplantation.

PMID- 7508094
TI  - New clinical-practice guidelines for the management of pain in patients with
      cancer.

PMID- 7508095
TI  - Hepatitis C virus antibody and hepatitis C viremia in pediatric dialysis patients
      in Taiwan.

PMID- 7508096
TI  - [Damage from reperfusion: no-reflow phenomenon].
AB  - It is well known that rapid myocardial reperfusion, obtained using thrombolysis
      and/or PTCA, continues to be the best treatment for evolving myocardial
      infarction. However, a number of experimental studies have drawn attention to the
      fact that myocardial recovery following reperfusion may be limited by the onset
      of numerous deleterious biochemical events which occur during reperfusion.
      Studies carried out after thrombolysis have shown that the perviousness of the
      vessel and the existence of flow at the level of the epicardial vessels do not
      necessarily correspond to the recovery of tissue perfusion since a perfusion
      defect may persist in the presence of angiographically documented anterograde
      flow. This discrepancy, which occurs during reperfusion, has been attributed to
      marked cellular enlargement caused by ischaemia both in irreversibly damaged
      areas and in those which may potentially recover. In basal conditions,
      endothelial-neutrophil interaction is inhibited by negatively charged molecules
      present on endothelial cell membranes and by the production of numerous anti
      inflammatory substances. During ischemia, on the other hand, anti-inflammatory
      and endogenous vasodilating substances are depleted in association with the
      appearance, on the surface of endothelial cells, of molecules favouring leukocyte
      adhesion. Of these the glycoprotein which has been characterized in greatest
      detail is the endothelial leukocyte adhesion molecule (ELAM 1) whose production
      and appearance on the endothelial surface is linked to cytokine-dependent
      endothelium activation. Ischemia may also stimulate the activation of neutrophils
      secreting chemiotactical and vasoconstricting factors, and cytotoxic compounds
      (reactive oxygen metabolites and proteolyte enzymes).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508097
TI  - [Dextran-induced anaphylactoid reaction (DIAR). 2 clinical cases].
AB  - Two cases of dextran-induced anaphylactoid reaction (grade II and III according
      to Ring e Messmer) are reported. Metabolic acidosis was an early symptom that
      must be considered on planning immediate therapy.

PMID- 7508099
TI  - High prevalence of anti-HCV among renal patients with or without renal failure.

PMID- 7508100
TI  - Wn mutation of c-kit receptor affects its post-translational processing and
      extracellular expression.
AB  - The W locus of mice encodes the c-kit receptor tyrosine kinase. Recently, we
      characterized a novel mutant allele, Wn, and demonstrated that the c-kit protein
      synthesized in Wn/Wn cultured mast cells (CMC) was reduced in size and not
      expressed on their surface (Tsujimura et al., 1993). In this study, we further
      examined biochemical nature of the mutant form of c-kit protein, by using Wn/Wn
      CMC and 293T cells transfected with Wn-type c-kit cDNA (c-kitWn). The c-kit
      product synthesized in Wn/Wn CMC was truncated almost all cytoplasmic domain and
      was less glycosylated. In c-kitWn-transected cells, both glycosylation and
      extracellular expression of c-kit protein was also impaired, however, no
      truncation was detected. These results indicate that Wn-mutant form of c-kit
      product is insufficient in maturation, which is associated with impairments in
      the transport to the plasma membrane, and retention of the mutant protein in
      endoplasmic reticulum is suggested. This is the first demonstration of the c-kit
      mutation affecting posttranslational processing its product.

PMID- 7508098
TI  - Pilot trial of FK 506 in the management of steroid-resistant nephrotic syndrome.
AB  - Seven patients with steroid-resistant nephrotic syndrome were treated with FK 506
      monotherapy. Four patients were children with focal sclerosing glomerulonephritis
      (FSGS). Three of these had evidence for chronic progressive renal disease
      consisting of interstitial fibrosis and tubular atrophy on pretreatment renal
      biopsies. Two patients had also failed cyclosporin A (CsA), two cyclophosphamide,
      and one chlorambucil prior to treatment with FK 506. Three patients were adults
      with mesangial proliferative, membranoproliferative, and membranous
      glomerulonephritis. Three patterns of response were noted: (1) a reduction in
      proteinuria to normal levels; (2) partial response (50% reduction) or; (3) no
      improvement. All patients except one experienced at least a 50% reduction in
      protein excretion at some time during FK 506 therapy. Two of the children and one
      adult reduced protein excretion to essentially normal values. One patient had no
      sustained reduction in protein excretion and is considered to be a treatment
      failure, although her protein excretion was approximately 50% of pretreatment
      values intermittently. The drug was generally well tolerated. The most common
      side-effect was nephrotoxicity, which was reversible. These encouraging results
      suggest that FK 506 monotherapy may be effective in controlling the proteinuria
      of some patients with steroid-resistant nephrotic syndrome. The use of this drug
      may extend our understanding of the role of T lymphocytes and cytokines in the
      pathogenesis of glomerulonephritis. Further study of this agent in a larger
      population of patients is warranted.

PMID- 7508101
TI  - Current perspectives on antiretroviral therapy.
AB  - Current estimates suggest that at least 1 million persons in the United States
      are infected with the human immunodeficiency virus (HIV), the cause of the
      acquired immunodeficiency syndrome. Knowledge of the life cycle of HIV has
      provided the fundamental information necessary to initiate programs that will
      identify drugs to treat the infection. Inhibition of reverse transcriptase
      represents the only strategy of proved clinical value. Three such drugs are
      available: zidovudine, didanosine, and zalcitabine. Zidovudine is the only proved
      agent for therapy of asymptomatic HIV infection; and for symptomatic disease,
      monotherapy with zidovudine must also be regarded as the first-line approach. For
      patients who are intolerant, are failing clinically, or have received prior long
      term treatment with zidovudine, monotherapy with didanosine or zalcitabine, or a
      combination of zidovudine and zalcitabine are alternatives. Progress is being
      made in the treatment of HIV infection, but the considerable challenge to affect
      the inexorable progressive nature of HIV disease remains daunting.

PMID- 7508102
TI  - The diagnostic use of low molecular weight keratin expression in sebaceous
      carcinoma.
AB  - Sebaceous carcinoma is an infrequent skin tumor and its histological features
      sometimes closely resemble those of squamous cell carcinoma (SCC) and basal cell
      epithelioma (BCE), which often leads to a misdiagnosis. In the present
      immunohistochemical study, however, sebaceous carcinoma exhibited quite a
      different expression of keratins from SCC and BCE. We immunohistochemically
      examined 26 excised specimens of sebaceous carcinoma, 10 of SCC and 12 of BCE of
      the eyelids, using two monoclonal antibodies against high molecular weight
      keratins, 34 beta B4 (68kd) and 34 beta E12 (56kd, 56.5kd, 58kd), and two
      monoclonal antibodies against low molecular weight keratins, 35 beta H11 (54kd)
      and CAM5.2 (39kd, 43kd, 50kd). The cases of sebaceous carcinoma were positive
      with 34 beta B4 (23%), 34 beta E12 (54%), 35 beta H11 (81%) and CAM5.2 (73%). Of
      the four anti-keratin antibodies used in this study, 35 beta H11 was negative in
      all cases of SCC or BCE. These findings indicate that when sebaceous carcinoma is
      suspected, but no fat staining appropriate materials are available, a monoclonal
      antibody against low molecular weight keratin, 35 beta H11 (54kd), can be a
      useful tool to immunohistochemically rule out both SCC and BCE.

PMID- 7508103
TI  - Plexiform schwannoma. Immunohistochemistry of Schwann cell markers, intermediate
      filaments and extracellular matrix components.
AB  - An immunohistochemical study using a comprehensive panel of antibodies to Schwann
      cell markers, intermediate filaments and extracellular matrix components has been
      performed on three cases of plexiform schwannoma. All tumour cells expressed S
      100 protein, Leu 7-HNK 1 antigen and vimentin; glial fibrillary acidic protein
      was detected in many tumour cells. In addition, expression of cytokeratin was
      also demonstrated in one case. The associated extracellular matrix was found to
      be reactive with antibodies to laminin, heparan sulfate proteoglycan,
      fibronectin, type I, III, IV and VI collagen. It is concluded that Schwann cells
      producing their own extracellular matrix are the main components of these
      tumours. The significance of the cytokeratin expression and the possible role of
      the extracellular matrix in regulating Schwann cells' proliferation in peripheral
      nerve tumours are discussed.

PMID- 7508105
TI  - Immunohistological detection of lymph node metastases in the testicular center as
      quick section diagnosis during retroperitoneal lymphadenectomy.
AB  - The object of this study was to determine whether the immunohistochemical
      detection of cytokeratin (CK)-positive cells is useful as quick section
      diagnosis, and whether the retroperitoneal lymphadenectomy (RLA) can be reduced
      by this method without any disadvantage for the patient. The RLA represents a
      combined diagnostic and therapeutic procedure for staging as well as removal of
      regional lymph node metastases in patients with malignant testis tumors. The
      disadvantage of the radical RLA is a 40 to 90% loss of potency. The risk of the
      reduced RLA is the relapse. The metastatic affection of the first retroperitoneal
      lymph node station, the so-called "sentinale" lymph nodes, allows a judgement for
      the remaining lymph nodes, and, therefore, for the extent of the necessary
      operation. The conventional frozen technique has a limited reliability, whereas
      the paraffin technique needs too much time. We used the immunohistochemistry as
      alternative method for the rapid as well as reliable evaluation of metastases. A
      group (7 cases) of 35 patients with non-seminomatous tumors of the testis was
      only treated by radical RLA after detection of CK-positive cells in the sentinale
      lymph nodes. The other patients were treated by modified RLA (20 cases) or
      reduced RLA (6 cases). The results were compared with a control group (48 cases)
      which was treated by radical RLA only. Using the modified RLA the relapse-free
      interval was not affected and the loss of ejaculation as a consequence of radical
      treatment could be avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508104
TI  - Immunohistologic detection of the primary follicle (PF) in human fetal and
      newborn lymph node anlages.
AB  - The primary follicle (PF) emerges as a globular nest of follicular dendritic
      cells (FDC) and lymphocytes in the lymph node anlage in the 16th gestational
      week. It increases in size with age but no germinal center is found until several
      months later, after birth. Using a panel of monoclonal antibodies, the authors
      have defined phenotypes of component cells of the PF. The PF contains a B-cell
      population including IgM+, CD20+, CD21+, and CD24+ cells, together with a T-cell
      population including CD3+, CD4+, CD5+, and CD8+ but no IgG+ cells. It also
      contains many CD5+ B cells and several IgD+ and alkaline phosphatase-positive
      cells but few CD15+, CD25+, CD30+, CD38+, and Ki-67+ cells. CD24+ and dendritic
      reticulum (DRC)-1+ cells show an irregular meshwork pattern in the PF. CD5+ B
      cells appear even before the formation of the PF and increase after formation of
      the PF. The lymphocytic phenotype of the PF is similar to that of the mantle zone
      of the secondary follicle. The phenotypic characteristics indicate that the PF
      appears as an aggregation of CD5+ B cells and plays an important role as the
      ancestor of the secondary follicle as well as helper T cells and FDC.

PMID- 7508106
TI  - Hyaline globules in uterine malignant mixed mullerian tumours. A diagnostic aid?
AB  - In order to evaluate the presence of hyaline globules (HGs) in uterine malignant
      mixed mullerian tumours (MMMT), and its possible diagnostic value in haematoxylin
      & eosin stained sections, a retrospective microscopic study of 38 cases (13
      homologous and 25 heterologous) was carried out. Intra- and extracellular HGs
      were found in 31 MMMT (81.6%), 8 homologous (61.5%) and 23 heterologous (92%). In
      addition, strong alpha-1-antitrypsin immunoreactivity was also noted in the HGs
      of 10 cases out of 13 investigated. In initial diagnostic curettage material, HGs
      were observed in 18 of 22 cases (81.8%), 6 of 9 homologous (66.7%) and 12 of 13
      heterologous (92.3%). In view of the high incidence of HGs in curettage
      specimens, their finding in haematoxylin & eosin stained sections could orientate
      a histopathologic preoperative diagnosis of MMMT, specially of heterologous type,
      and may be considered a diagnostic tool in order to indicate an early, planned
      therapy and staging in these neoplasms of poor prognosis.

PMID- 7508107
TI  - Expression of beta-1 integrins on tumor cells of invasive ductal breast
      carcinoma.
AB  - The integrins are transmembrane alfabeta heterodimers mediating cell-cell as well
      as cell-extracellular matrix interactions. The present study was designed to
      analyse the expression of beta-1 integrins on cryostat sections of invasive
      ductal carcinomas not otherwise specified by avidin-biotin complex
      immunoperoxidase technique, and to compare it with the morphometric prognostic
      index (MPI). The results show that the expression of beta-1 integrins is
      heterogeneous in the tumors. This heterogeneity was observed in quantitative and
      qualitative staining pattern. There was an absent expression of beta-1 integrins
      in 22 out of 55 tumors while 33 showed staining, weak on 23 cases and strong on
      10 infiltrative ductal carcinomas. Statistical analysis pointed to some
      correlation of beta-1 integrins with some morphometric parameters. Low or absent
      expression of beta-1 integrins correlated significantly with tumors exceeding 2
      cm (p < 0.0245). Moreover, a larger proportion of tumors with positive lymph
      nodes showed absence of beta-1 expression compared with negative lymph node, and
      this was also statistically significant (p < 0.0076). Correlation between mitotic
      activity index and staining intensity for beta-1 integrins was not found (p <
      0.372). When tumors with different beta-1 expression were subdivided according to
      MPI values into two groups, one group with a low-risk, < 0.6, and second with a
      high risk, > 0.6, concordance in prognostic value was shown between MPI and beta
      1 expression (p < 0.0193). These results support the idea that loss of beta-1
      integrins correlates with the invasive and metastatic potential of tumor cells.

PMID- 7508108
TI  - Kinetic analysis of molecular interconversion of immunosuppressant FK506 by high
      performance liquid chromatography.
AB  - High-performance liquid chromatography of FK506, a macrolide immunosuppressant,
      was performed on a reversed-phase column. The peak was broad with the column kept
      at room temperature, which was accounted for by slow interconversion between the
      two forms of FK506. With the use of a heated column, a sharp peak was observed
      because of the rapid interconversion at high temperature. When the column was
      cooled to 0 degree C, two sharp peaks were observed because essentially no
      interconversion occurred at 0 degree C during elution. Analysis of the
      chromatograms obtained at various eluant flow rates indicated that the conversion
      of the two forms follows first-order kinetics, and the apparent activation
      energies for the conversions were calculated. The interconvertibility between the
      two molecular forms may be related to the immunosuppressive activity.

PMID- 7508109
TI  - Pancreatic protein hypersecretion and elevated plasma CCK: prerequisites for
      increased pancreatic growth?
AB  - This study was undertaken to establish if a correlation exists between chronic
      elevated pancreatic secretion and growth of the pancreas. Rats provided with
      jugular, pancreatic, biliary, duodenal, or ileal cannulas were fed throughout the
      experiment with a liquid diet continuously infused into the duodenum. Four days
      after surgery, control rats and those infused with cerulein (CE) 0.45
      microgram/kg/h had their pancreatic juice returned into the duodenum. Two other
      groups had their pancreatic juice either totally diverted outside (DO) or
      returned into the ileum (DI). In all groups, bile was returned into the duodenum.
      Pancreatic juice was collected every 4 h for 4 days with volume and protein
      determined. After 4 days, rats were killed and their pancreata were evaluated for
      weight and contents of DNA, RNA, protein, amylase, and chymotrypsinogen. The
      average volumes/4 h were significantly increased by 259, 241, and 270% in DO, DI,
      and CE rats, respectively. Protein output remained at control levels in DO rats,
      whereas increases of 200 and 90% above control values were observed in DI and CE
      rats, respectively, during the last periods of collection. Constant drainage of
      pancreatic juice outside (DO) had no effect on pancreatic growth; on the
      contrary, its reinfusion into the ileum and constant cerulein infusion were
      associated with impressive growth of the pancreas, with cerulein being the most
      potent stimulus. In conclusion these data support the hypothesis that increased
      protein output is associated with pancreatic growth, a phenomenon mediated by
      endogenous cholecystokinin.

PMID- 7508110
TI  - Is bile salt-dependent lipase concentration in serum of any help in pancreatic
      cancer diagnosis?
AB  - The diagnostic value of bile salt-dependent lipase for pancreatic diseases was
      tested in sera of 187 patients. Of these patients, 76 suffered from pancreatic
      carcinoma, 43 from nonmalignant liver diseases (cirrhosis and chronic hepatitis),
      18 from acute pancreatitis, and 20 from chronic pancreatitis. The remaining
      subjects were controls without pancreatic pathology. Bile salt-dependent lipase
      was determined by a sandwich enzyme-linked immunosorbent assay using polyclonal
      antibodies. Amylase and CA 19-9 antigen were also determined. In sera from
      control patients, the mean level of bile salt-dependent lipase was 1.5
      micrograms/L. This level is quite similar to that of patients with benign liver
      diseases (1.1 micrograms/L) and with chronic pancreatitis (1.4 micrograms/L), but
      it was raised to 3.5 micrograms/L in patients with acute pancreatitis and
      decreased to 0.5 microgram/L in subjects with pancreatic adenocarcinoma. Thirty
      percent of control subjects and 73% of cancer patients had a bile salt-dependent
      lipase serum level below the cutoff value of 0.5 microgram/L. In acute
      pancreatitis, 11 of 16 subjects had levels above 1.5 micrograms/L. Amylase level
      largely increased in acute pancreatitis but was normal in all other groups.
      Concerning CA 19-9 antigen, 65% of control patients and > 80% of patients with
      nonmalignant pancreatic or liver diseases had normal levels. In sera from cancer
      patients, 80% presented with high levels. Accordingly, 36 of 38 patients with
      pancreatic cancer had either low serum levels of bile salt-dependent lipase (<
      0.5 microgram/L) or high values of CA 19-9 antigen (> 37 U/ml; sensitivity
      95%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508111
TI  - Reversibility of pancreatitis after temporary pancreaticobiliary duct obstruction
      in rats.
AB  - Pancreaticobiliary duct (PBD) obstruction in rats is associated with
      hyperamylasemia, hyperlipasemia, pancreatic edema, inflammation, and subcellular
      enzyme redistribution in < 24 h. The purpose of our study was to investigate
      whether these changes are reversible. A catheter was placed in the distal PBD and
      tunneled subcutaneously to the nape of the neck where flow could be controlled.
      The distal end was secured into the duodenum. Animals were divided into five
      groups: Group I, free flow for 48 h; Group II, catheter obstruction for 24 h;
      Group III, obstruction for 48 h; Group IV, obstruction for 24 h followed by free
      flow for 24 h; Group V, obstruction for 24 h followed by free flow for 48 h.
      After killing, amylase and lipase were measured, pancreatic water content was
      determined, and morphologic damage was graded blindly for edema, inflammation,
      acinar dilatation, and cell injury. Both groups with temporary obstruction showed
      less morphologic damage than groups studied directly after obstruction.
      Pancreatic water content was lower after reversal than after a 48-h obstruction.
      Serum amylase and lipase peaked after 24-h obstruction and then dropped with
      either treatment. We conclude that continuous obstruction causes progressive
      pancreatic damage, whereas releasing the obstruction results in reversal of early
      structural and functional changes.

PMID- 7508113
TI  - Immunohistochemical assessment of proliferative activity in adrenocortical
      neoplasms.
AB  - Although many histologic criteria have been utilized to help distinguish benign
      from malignant adrenocortical tumors, it still may be difficult to assess the
      biologic potential of a given tumor. We evaluated 19 adenomas and 15 primary
      carcinomas with the avidin-biotin complex peroxidase method utilizing formalin
      fixed, paraffin-embedded tissues with monoclonal antibodies for proliferating
      cell nuclear antigen (PC10) and Ki-67 (MIB 1) to determine if staining for these
      antigens could be used to help differentiate benign from malignant adrenocortical
      neoplasms. We also evaluated whether these markers could be used as prognostic
      indicators. Labeling indices for both PCNA and Ki-67 were determined by
      enumerating 1000 tumor cells, and expressed as a percentage of cells with nuclear
      staining. A PCNA and a Ki-67 score was obtained by the product of the staining
      intensity (0-3+) and the extent of nuclear staining, expressed as an estimate of
      the percentage of cells staining. Both PCNA and Ki-67 score and labeling index
      were correlated with mitotic counts, histologic diagnosis, and clinical outcome.
      Follow-up period for patients ranged from 4 months to 12 years with a mean of 25
      months. Mitotic counts correlated with histologic diagnosis and clinical outcome.
      Both Ki-67 score and labeling index were significantly higher in malignant than
      in benign tumors, and correlated with mitotic counts and clinical outcome. There
      was a strong correlation between Ki-67 score and labeling index, indicating that
      Ki-67 score may be a more rapid and equally accurate method of estimating
      proliferative index of a tumor. PCNA score and labeling index did not correlate
      with histologic diagnosis or clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508112
TI  - Cholecystokinin JMV-180 and caerulein effects on the pancreatic acinar cell
      cytoskeleton.
AB  - We previously demonstrated that the supramaximally effective concentrations of
      caerulein caused marked changes in the apical cytoskeleton of the rat pancreatic
      acinar cell. These changes included ablation of microvilli, the terminal actin
      web, and intermediate filament bands. The present study was designed to elucidate
      part of the intracellular signalling mechanism mediating these changes. For these
      studies we used a cholecystokinin (CCK) analogue, CCK-JMV-180, that has been
      previously demonstrated not to inhibit enzyme secretion and to prevent the
      inhibition caused by caerulein. We investigated the effects of CCK-JMV-180 alone
      and in combination with supramaximal concentrations of caerulein on the
      morphology of the apical structures, on 1,2-diacylglycerol production (a measure
      of phospholipase C activity), and on amylase secretion in rat pancreatic acini.
      Supramaximally effective concentrations of caerulein caused inhibition of enzyme
      secretion. CCK-JMV-180 had no effect on the ultrastructure of the apical region
      of the acinar cell and it prevented the ablation of apical cytoskeleton induced
      by a supramaximal concentration of caerulein (10 nM). CCK-JMV-180 inhibited the
      increase in 1,2-diacylglycerol formation and the inhibition of amylase release
      caused by 10 nM caerulein. Mimicking the effect of 1,2-diacylglycerol on
      activation of protein kinase C with phorbol 12-myristate 13-acetate and
      reproducing changes in [Ca2+]i caused by 10 nM caerulein with 100 nM bombesin did
      not alter the apical cytoskeleton. These results suggest that the cytoskeletal
      changes observed with inhibitory concentrations of caerulein are caused by the
      phospholipase C effects of caerulein on membrane phospholipids.

PMID- 7508114
TI  - Immunohistochemical evaluation of dystrophin expression in small round cell
      tumors of childhood.
AB  - Dystrophin, the protein product of the Duchenne muscular dystrophy locus, is a
      major component of the subsarcolemmal cytoskeleton in skeletal muscle cells and
      is a relatively muscle specific protein. We evaluated, retrospectively, the
      expression of dystrophin in 23 small round cell tumors of childhood including: 9
      rhabdomyosarcomas, 4 neuroblastomas, 1 ganglioneuroblastoma, 2 small noncleaved
      cell lymphomas, 1 lymphoblastic lymphoma, 2 medulloblastomas, 2 primitive
      neuroectodermal tumors, 1 Wilms' tumor, and 1 undifferentiated sarcoma. Frozen
      sections were stained by the avidin biotin immunoperoxidase technique using a
      commercially available monoclonal antibody NCL-DYS1 (Novocastra) that recognizes
      the mid-rod domain (between amino acids 1181 and 1388) of human dystrophin.
      Positive controls were represented by frozen sections of normal skeletal muscle.
      Negative controls consisted of substituting the dystrophin antibody for normal
      rabbit serum. Eight of nine rhabdomyosarcomas revealed positivity whereas, none
      of the other tumors stained for dystrophin. This study provides evidence that
      monoclonal antibodies to dystrophin may be a potential useful addition to the
      panel of muscle markers used to diagnose small round cell tumors of childhood.

PMID- 7508115
TI  - Expression of transforming growth factor-alpha, epidermal growth factor and the
      epidermal growth factor receptor in adenocarcinoma of the prostate and benign
      prostatic hyperplasia.
AB  - The present immunohistochemical study examines the expression of TGF alpha, EGF,
      and the EGF receptor in prostatic tissues obtained from patients with either
      benign prostatic hyperplasia (BPH) or adenocarcinoma of the prostate. Frozen
      sections were cut at 5 microns and were incubated with monoclonal antibodies
      directed against TGF alpha, EGF, or the EGF receptor. The remainder of the
      staining procedure was performed with an avidin-biotin-complex peroxidase
      procedure. Strong TGF alpha expression was not detected in any of the 15 BPH
      specimens examined or in the normal/hyperplastic tissue intermixed within the
      adenocarcinomas. In contrast, malignant cells in 9 of 11 adenocarcinomas strongly
      expressed TGF alpha. EGF reactivity was observed in both hyperplastic and
      malignant epithelial tissues. EGF receptor expression was strongest along the
      basal aspects of cells of normal or hyperplastic glands. Although most malignant
      cells also were positive for the EGF receptor the level of staining was less than
      that observed in cells forming normal or hyperplastic glands. These results
      suggest that EGF and the EGF receptor may be components of an autocrine/paracrine
      regulatory pathway involved in hyperplastic and/or malignant disease of the
      prostate. The finding that TGF alpha is expressed only in malignant cells
      suggests that TGF alpha may represent a locally active autocrine regulator of
      malignant prostate cells.

PMID- 7508116
TI  - The predictive value of ERICA in breast cancer recurrence. A univariate and
      multivariate analysis.
AB  - In breast cancer, primary tumor size (T), the number of lymph node metastases
      (#N), the biochemical estrogen (ER), and progesterone (PGR) receptor status have
      all been important prognostic variables. We evaluated the significance of the
      immunocytochemical measurement of estrogen receptors suing the ERICA method. To
      determine the relative prognostic value of these variables T, #N, ER, PGR, ERICA
      and adjuvant treatment, (ADJ), univariate and multivariate analyses of disease
      free survival (DFS) were performed for 154 primary breast cancer patients who
      were diagnosed in 1985 to 1986 at Women's College Hospital and followed
      prospectively. We analyzed ERICA results using different classification systems,
      and assessed clinical cut points for the univariate and multivariate context. The
      variables consistently included in the best Cox stepwise regression are T, (p <
      0.01), ADJ (p < 0.01), #N (p < 0.01), and ERICA (p < 0.01). There was weaker
      evidence of an association between DFS and the biochemically determined ER; ER
      was not included in the model with a cut point at 10 fmol mg of protein. This
      illustrates the value of the ERICA method in predicting outcome, and suggests the
      need to consider ERICA values for clinical decision making.

PMID- 7508117
TI  - Comparison of two antibodies for evaluation of estrogen receptors in paraffin
      embedded tumors.
AB  - Estrogen receptor (ER) content in breast cancer specimens is correlated with a
      prolonged disease free survival and increased likelihood of response to hormone
      therapy. Relatively few anti-ER antibodies are currently available for use in
      formalin-fixed, paraffin-embedded tissue. Recently, a new anti-ER monoclonal
      antibody (ERID5; AMAC, Westbrook, Maine) was generated which requires antigen
      retrieval by microwave oven heating for detection in routinely processed tissue.
      The specific aim of this study was to compare the ERID5 antibody with the
      commercially available rat monoclonal (ER-ICA; Abbott, Chicago, IL) which
      requires proteolytic enzyme digestion for detection in paraffin-embedded tissue.
      Sections from 20 cases of primary breast carcinoma previously assayed by dextran
      coated charcoal (DCC) analysis were examined. Quantitation of ER antibody
      staining was performed without knowledge of the DCC values. Specimens containing
      > or = 20% specifically stained malignant cells were considered ER positive. The
      sensitivity and specificity of visual ER-ICA immunostaining were 57% and 83%,
      respectively. The sensitivity and specificity of visual ERID5 immunostaining were
      93% and 50%, respectively. The predictive value of positive staining was 89% for
      the ER-ICA antibody and 81% for the ERID5 antibody. The predictive value of
      negative staining was 45% for the ER-ICA antibody and 75% for the ERID5 antibody.
      Previous studies have demonstrated a linear correlation between DCC values and
      the positive nuclear area (PNA) generated by image analysis for ER-ICA
      immunostaining. In the present study, a similar correlation between DCC value and
      ERID5 percentage PNA was observed (R = 0.670; P < 0.001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7508118
TI  - Synaptic relationship between substance P and the substance P receptor: light and
      electron microscopic characterization of the mismatch between neuropeptides and
      their receptors.
AB  - Light microscopic studies have demonstrated significant mismatches in the
      location of neuropeptides and their respective binding sites in the central
      nervous system. In the present study we used an antiserum raised against a
      synthetic peptide corresponding to the carboxyl-terminal tail of the substance P
      (SP) receptor (SPR) to further explore the relationship between a neuropeptide
      and its receptor. Light microscopy revealed an excellent correlation between the
      patterns of SPR immunoreactivity and of 125I-labeled SPR-binding sites in the
      central nervous system. The SPR appeared to be exclusively expressed by neurons;
      in fact, the SPR decorates the somatic and dendritic surface of neurons,
      producing Golgi-like images. Electron microscopic analysis in cortex, striatum,
      and spinal cord revealed that approximately 70% of the surface membrane of
      immunoreactive neurons is SPR laden. Simultaneous electron microscopic labeling
      of SP and SPR demonstrated significant mismatch at the synaptic level. Although
      some SP terminals contacted SPR-immunoreactive membrane, no more than 15% of the
      SPR-laden membrane apposed synaptic terminals. These results suggest that in
      contrast to more "classical" central and peripheral nervous system synapses,
      wherein the receptor immediately apposes the site of neurotransmitter storage and
      release, much of the surface of SPR-expressing neurons can be targeted by SP that
      diffuses a considerable distance from its site of release.

PMID- 7508119
TI  - CD40 ligand expression is defective in a subset of patients with common variable
      immunodeficiency.
AB  - Common variable immunodeficiency (CVI) is characterized by hypogammaglobulinemia
      and recurrent bacterial infections due to failure of CVI B cells to differentiate
      in vivo into immunoglobulin-secreting plasma cells. We hypothesized that T-cell
      dysfunction resulting in abnormal contact-mediated B-cell activation may play a
      prominent role in the failure of CVI B cells to produce specific antibody. We
      have previously shown that B-cell proliferation and IgE production after
      stimulation with anti-CD40 and interleukin (IL) 4 were normal in 22 CVI patients
      evaluated, indicating that CVI B cells respond to signals delivered via CD40.
      Here we report that CD40 ligand (gp39) mRNA expression by activated lymphocytes
      from CVI patients (n = 31) as a group was significantly depressed (P < 0.0001)
      compared with normal controls (n = 32). gp39 mRNA expression by activated
      lymphocytes from 13 CVI patients fell below the normal control range. T-cell
      surface expression of functional gp39 protein was correspondingly low in those
      patients with gp39 mRNA levels below normal control range and normal in patients
      with gp39 mRNA levels within normal control range. In CVI patients as a group,
      gp39 mRNA levels correlated with IL-2 mRNA levels (P < 0.002, r = 0.6) and
      production (P < 0.001, r = 0.7) but not with gene expression or production of
      other lymphokines evaluated, suggesting an as-yet-undetermined association
      between gp39 and IL-2 gene regulation. Of the 13 patients whose activated T cells
      exhibited gp39 mRNA expression below the normal control range, 2 had normal T
      cell-derived lymphokine production, whereas the remaining 11 exhibited broader T
      cell dysfunction, resulting in IL-2 deficiency, and in some patients deficient
      production of other lymphokines as well, reflecting a heterogeneity in the
      underlying mechanisms leading to depressed gp39 expression in these patients. The
      observation that both gene and surface expression of gp39 by activated T cells is
      depressed in a subgroup of CVI patients suggests that inefficient signaling via
      CD40 may be responsible, in part, for failure of B-cell differentiation in these
      patients.

PMID- 7508120
TI  - A single negative charge within the pore region of a cGMP-gated channel controls
      rectification, Ca2+ blockage, and ionic selectivity.
AB  - Ca2+ ions control the cGMP-gated channel of rod photoreceptor cells from the
      external and internal face. We studied ion selectivity and blockage by Ca2+ of
      wild-type and mutant channels in a heterologous expression system. External Ca2+
      blocks the inward current at micromolar concentrations in a highly voltage
      dependent manner. The blockage at negative membrane voltages shows a steep
      concentration dependence with a Hill coefficient of approximately 2. The blockage
      from the internal face requires approximately 1000-fold higher Ca2+
      concentrations. Neutralization of a glutamate residue (E363) in the putative pore
      region between transmembrane segments H4 and H5 induces outward rectification and
      changes relative ion conductances but leaves relative ion permeabilities nearly
      unaffected. The current blockage at -80 mV requires approximately 2000-fold
      higher external Ca2+ concentrations and the voltage dependence is almost
      abolished. These results demonstrate that E363 represents a binding site for
      monovalent and divalent cations and resides in the pore lumen.

PMID- 7508122
TI  - American origins.

PMID- 7508121
TI  - Overexpression of parathyroid hormone-related protein in the skin of transgenic
      mice interferes with hair follicle development.
AB  - Parathyroid hormone-related peptide (PTHrP) was initially discovered as the cause
      of the syndrome of humoral hypercalcemia of malignancy. Subsequently, the PTHrP
      gene has been shown to be expressed in a wide variety of normal tissues,
      including skin. Because the biological function of PTHrP in skin remains unknown,
      we used the human keratin 14 promoter to target overexpression of PTHrP to the
      skin of transgenic mice. We achieved a 10-fold level of overexpression in skin,
      and human keratin 14 promoter-PTHrP transgenic mice displayed a disturbance in
      normal hair follicle development. These mice either failed to initiate follicle
      development or showed a delay in the initiation of follicles. These findings
      suggest that PTHrP normally plays a role in the early stages of hair follicle
      development and support previous speculation that the peptide may function in
      regulating cellular differentiation.

PMID- 7508124
TI  - CP-96,345, a substance P antagonist, inhibits rat intestinal responses to
      Clostridium difficile toxin A but not cholera toxin.
AB  - Toxin A from Clostridium difficile mediates acute inflammatory enterocolitis in
      experimental animals, while cholera toxin causes noninflammatory secretory
      diarrhea. The purpose of this study was to investigate whether an antagonist to
      the peptide substance P, a constituent of primary sensory neurons known to
      participate in inflammatory responses, would inhibit toxin A-mediated enteritis
      in the rat ileum. Pretreatment of rats with CP-96,345 (2.5 mg per kg of body
      weight), a substance P antagonist, dramatically inhibited fluid secretion (P <
      0.01) and mannitol permeability (P < 0.01) in ileal loops exposed to toxin A. The
      protective effects, which were dose dependent, caused a significant reduction of
      inflammation in the lamina propria, reduction of the necrosis of intestinal
      epithelial cells, and complete inhibition of toxin A-mediated release of rat mast
      cell protease II, a specific product of rat mucosal mast cells. An inactive
      enantiomer of the substance P antagonist, CP-96,344, had no effect. In contrast,
      pretreatment with CP-96,345 had no inhibitory effect on the intestinal effects
      caused by administration of cholera toxin into the ileal loops. From these data,
      we conclude that the peptide substance P is involved in the secretory and
      inflammatory effects of toxin A but not of cholera toxin.

PMID- 7508123
TI  - Oncogene activation of human keratin 18 transcription via the Ras signal
      transduction pathway.
AB  - Keratin 8 (K8) and keratin 18 (K18) are intermediate filament proteins normally
      expressed in simple epithelial tissues and persistently expressed in a wide
      variety of carcinomas. Ectopic expression of K8 and K18 occurs in some epidermal
      and murine skin carcinomas induced by chemical carcinogenesis or oncogenic ras
      expression. We show here that K18 is a direct target of the Ras signal
      transduction pathway, by demonstrating that activated Ha-Ras, as well as
      activated Src, Lck, or Raf, stimulates the transcription of K18. This activation
      is mediated by an enhancer element containing essential and closely spaced Ets
      and AP-1 transcription factor binding sites. Oncogene activation of K18
      transcription provides a molecular explanation for the persistent and sometimes
      unexpected expression of K18 in such a wide variety of tumors.

PMID- 7508125
TI  - Light-regulated, tissue-specific immunophilins in a higher plant.
AB  - In addition to their application in organ transplantation, immunosuppressive
      drugs are valuable tools for studying signal transduction in eukaryotic cells.
      Using affinity chromatography, we have purified immunosuppressive drug receptors
      (immunophilins) from fava bean. Proteins belonging to both major classes of the
      immunophilin family identified from animal sources [FK506- and rapamycin-binding
      proteins (FKBPs) and cyclophilins] were present in this higher plant. FKBP13, the
      most abundant FKBP family member in leaf tissues, was not detected in root
      tissues, whereas other FKBPs were present in both tissues. While the abundance of
      cyclophilin A in leaves was similar to that in roots, cyclophilin B/C was
      expressed at a much higher level in leaf tissues than in root tissues.
      Subcellular localization of immunophilins in mesophyll cells showed that
      chloroplasts contained FKBP13 and cyclophilin B/C but not other members, which
      explains the preferential expression of these two proteins in leaves over roots.
      The abundance of chloroplast-localized immunophilins, FKBP13 and cyclophilin B/C,
      was regulated by light. Although etiolated leaves produced detectable levels of
      cyclophilin B/C, they did not express FKBP13. Illumination of etiolated plants
      dramatically increased the expression of both FKBP13 and cyclophilin B/C. The
      light-induced expression of FKBP13 is closely correlated with the accumulation of
      chlorophyll in the leaf tissue. Our findings suggest that FKBP13 and cyclophilin
      B/C may play a specific role in chloroplasts.

PMID- 7508127
TI  - An immunohistochemical study of the reconstruction of the peripheral nervous
      system during the newt tail regeneration.

PMID- 7508126
TI  - Endothelial cells are activated by cytokine treatment to kill an intravascular
      parasite, Schistosoma mansoni, through the production of nitric oxide.
AB  - Like many pathogens that undergo an intravascular stage of development, larvae of
      the helminth parasite Schistosoma mansoni migrate through the blood vessels,
      where they are in close contact with endothelial cells. In vitro exposure of
      murine endothelial cells to various cytokines (interferon gamma, tumor necrosis
      factor alpha, and interleukin 1 alpha or 1 beta) resulted in their activation to
      kill schistosomula through an arginine-dependent mechanism involving production
      of nitric oxide (NO). Cytokine-treated endothelial cells showed increased
      expression of mRNA for the inducible form of the NO synthase, and both NO
      production and larval killing were suppressed by treatment with competitive
      inhibitors. The effector function of cytokine-treated endothelial cells was
      similar to that of activated inflammatory tissue macrophages, although activation
      appeared to be differentially regulated in these two cell types. Activated
      endothelial cells killed older (18-day) forms of the parasite, such as those
      currently thought to be a primary target of immune elimination in the lungs of
      mice previously vaccinated with radiation-attenuated cercariae, as well as newly
      transformed larvae. In C57BL/6 mice, which become resistant to S. mansoni
      infection as a result of vaccination with irradiated cercariae, endothelial cell
      morphology characteristic of activation was observed in the lung by 1-2 weeks
      after challenge infection. Similar endothelial cell changes were absent in P
      strain mice, which do not become resistant as a result of vaccination. Together,
      these observations indicate that endothelial cells, not traditionally considered
      to be part of the immune system, may play an important role in immunity to S.
      mansoni and, by means of NO-dependent killing, could serve as effectors of
      resistance to other intravascular pathogens.

PMID- 7508129
TI  - The relationship between migrating neural crest cells and growing limb nerves in
      the developing chick forelimb.

PMID- 7508128
TI  - Expression and regulation of keratins in the wound epithelium and mesenchyme of
      the regenerating newt limb.

PMID- 7508130
TI  - Neural crest cell migration into the limb bud of avian embryos.
AB  - The colonization of limb buds by neural crest cells was studied in quail-chick
      chimeras and in chick embryos using HNK-1 and DiI staining and the LD-DOPA
      reaction. Two populations of neural crest cells were found to colonize the limb
      bud. They migrate successively and use different routes of migration. The first
      population migrates within the limb bud subectodermally at stages before the limb
      is innervated. In the wing bud the migration route is localized postaxially and
      in the leg bud preaxially. Two cell types were identified differentiating from
      this first population: melanoblasts and Merkel cells. The second population of
      crest cells invades the limb bud at a later stage. These cells follow the routes
      of ingrowing nerves and migrate along a dorsal and a ventral path which
      correspond to the position of nerves for extensor and flexor muscles. Crest cells
      were found here also in the absence of nerves. Schwann cells and terminal glial
      cells develop from this second population of neural crest cells.

PMID- 7508131
TI  - Organic nitrates and compounds that increase intraplatelet cyclic guanosine
      monophosphate (cGMP) levels enhance the antiaggregating effects of the stable
      prostacyclin analogue iloprost.
AB  - The present study investigated the effect of a combination between the stable
      prostacyclin (PGI2) analogue iloprost and compounds, glyceryl trinitrate (GTN)
      and L-arginine-, which enhance the intraplatelet cyclic guanosine monophosphate
      (cGMP) levels on platelet aggregation, release reaction and cyclic nucleotide
      content: in particular cyclic adenosine monophosphate (cAMP) and cGMP. Iloprost
      inhibited in a dose-dependent way the platelet aggregation in response to
      collagen, adenosine diphosphate (ADP) and adrenaline and it increased the
      intraplatelet cAMP concentrations. GTN directly decreased the platelet responses
      and increased the intraplatelet levels of both cGMP and cAMP. GTN (20 x 10(-6)
      mol/l) and L-arginine (0.2 x 10(-3) mol/l) potentiated the inhibitory effects of
      iloprost on platelet aggregation and release reaction. Our results suggest: 1. A
      synergistic effect of the simultaneous increase of both cAMP and cGMP on the
      biochemical steps involved in the inhibition of the platelet response; 2. An
      influence of cGMP on cAMP accumulation.

PMID- 7508133
TI  - [The child who did not know how to play].
AB  - Through the report of an analytic treatment of a 6 year old boy who could not
      play, the author attempts to illustrate and conceptualize how the associative
      playing, so typical of the child psychoanalyst, enables a creation/retrieval of a
      truth and of an interior life, through very complex mutual identifications.

PMID- 7508132
TI  - Effects of glucocorticoid on signalling by prostaglandin E2 in osteoblast-like
      cells.
AB  - It is well-known that osteoporosis is a common complication of patients with
      glucocorticoid excess. We previously reported that dexamethasone inhibits Ca2+
      influx induced by prostaglandin E2 (PGE2), a potent bone resorbing agent, in
      osteoblast-like MC3T3-E1 cells (O. Kozawa, H. Tokuda, J. Kotoyori, A. Suzuki, Y.
      Ito and Y. Oiso, Prostagland Leuk Essent Fatty Acids, in press). In the present
      study, we examined the effects of dexamethasone on cyclic adenosine monophosphate
      (cAMP) accumulation and phosphoinositide hydrolysis by PGE2 in MC3T3-E1 cells.
      The pretreatment with dexamethasone significantly inhibited cAMP accumulation
      stimulated by PGE2 in a dose-dependent manner in the range between 10 pM and 1 nM
      in MC3T3-E1 cells. This effect of dexamethasone was dependent on the time of
      pretreatment up to 8 h. Dexamethasone also inhibited the cAMP accumulation
      induced by NaF, an activator of guanosine triphosphate (GTP)-binding protein, or
      forskolin which directly activates adenylate cyclase. In contrast, dexamethasone
      had little effect on the formation of inositol phosphates stimulated by PGE2 in
      MC3T3-E1 cells. These results strongly suggest that glucocorticoid modulates the
      signal transduction by PGE2 in osteoblast-like cells and that it inhibits PGE2
      induced cAMP production without affecting PGE2-induced phosphoinositide
      hydrolysis.

PMID- 7508134
TI  - [Incidence of the impact of cognitive processes on the symbolization process;
      their evolution during treatment].
AB  - This article depicts the therapy of a child whose lack of language is related
      both to cognitive deficiencies and psychological conflicts. The relation between
      the two, the place of gesture in his symbolic system and the factors of evolution
      are the main points examined hereafter.

PMID- 7508135
TI  - [Regulatory factors of selective growth and death of oocytes].

PMID- 7508136
TI  - Effects of interleukin 4 on human B-cell growth and differentiation.

PMID- 7508137
TI  - The effect of diet on aflatoxin B1 binding to hepatic macromolecules in rats.
AB  - Fischer 344 rats were fed a low-fat high carbohydrate diet (HC), an isocaloric
      fat-containing diet (IC), a hypercaloric fat-containing diet (HF) or rat chow.
      Covalent binding of AFB1 to liver DNA, RNA and total proteins was investigated in
      a 24 hour period following administration of a single intraperitoneal dose of
      AFB1 (1 mg/kg body weight). AFB1 binding to nucleic acids was greatest in the HC
      and was generally significantly lower (p < 0.05) in the HF, IC and rats fed chow.
      The results suggest that fat decreases hepatic macromolecular adduct formation by
      inhibiting activation of AFB1 to the epoxide or by enhancing the activity of
      detoxification pathways.

PMID- 7508138
TI  - Effects of twenty-three drugs on the metabolism of FK506 by human liver
      microsomes.
AB  - We investigated the effects of 23 drugs on the metabolism of FK506 by human liver
      microsomes. Acyclovir, amphotericin B, cefixime, cefotaxime, ciprofloxacin,
      cyclosporin A, diltiazem, enoxacin, erythromycin, ethinyl estradiol, fluconazole,
      fosfomycin, kanamycin, lincomycin, loxoprofen, minocyclin, nifedipine,
      nilvadipine, norethindrone, ofloxacin, phenobarbital, prednisolone, or rifampicin
      was added to the reaction media at equimolar or at ten times an excess molar
      ratio of the substrate concentration; their effects on FK506 metabolism were
      examined. Drugs known to be the substrate of cytochrome P-450 3A inhibited the
      metabolism of FK506, and among the drugs tested, the inhibition by cyclosporin A
      and nifedipine was the strongest.

PMID- 7508139
TI  - [Hepatitis C virus antibodies in chronic non-alcoholic liver disease].
AB  - The presence of hepatitis C virus antibodies was studied in 64 patients with non
      alcoholic liver disease and found in 11 (17%). The greater frequency of positive
      antibodies was found among patients with cryptogenetic liver disease, specially
      those without serum auto-antibodies (32%). The antibody was unusually found (0 to
      11%) in non alcoholic liver diseases of other etiologies. It is concluded that
      hepatitis C virus chronic infections may be the etiology of an important number
      of non alcoholic chronic liver diseases.

PMID- 7508140
TI  - [Prevalence of hepatitis C virus antibodies in a hemodialysis unit].
AB  - The prevalence of hepatitis C antibody was studied using the EIA 2 Abbott assay
      in patients and staff of the San Juan de Dios Hospital Hemodialysis Unit. The
      antibody was detected in 29.8% of patients, no member of the staff had positive
      antibodies. Patients with a positive antibody had been on hemodialysis for a
      longer time than those with a negative test (53.3 +/- 18.8 vs 37.9 +/- 33.5
      months respectively). No differences in the number of transfusions received were
      observed between patients with positive or negative antibodies. Hepatitis B
      surface antigen was detected in 2 patients, with negative hepatitis C virus
      antibody. No clinical evidence of liver disease was found among patients with
      positive antibodies.

PMID- 7508141
TI  - [Met-enkephalin and substance P. Comparison of CSF levels in patients with
      chronic pain based on a sampling procedure].
AB  - The purpose of this study was to evaluate the Met-enkephalin and the SP-like
      immunoreactivity levels in the CSF of 16 patients suffering from chronic
      sciatalgia and to compare them with those of 8 control subjects. Eight of the
      patients had a ventriculo-peritoneal shunt which made it possible to collect
      samples of CSF painlessly. For the others patients and controls, CSF samples were
      collected by lumbar puncture. The results showed that there was no difference in
      the Met-enkephalin and SP levels whatever the method of sample collection. On the
      other hand, SP-like immunoreactivity was lower in patients suffering from chronic
      pain.

PMID- 7508142
TI  - Mining treasures from 'junk DNA'.

PMID- 7508143
TI  - Magnetic resonance microscopy of embryonic cell lineages and movements.
AB  - Key events in vertebrate embryogenesis are difficult to observe in many species.
      High-resolution magnetic resonance imaging was used to follow cell movements and
      lineages in developing frog embryos. A single cell was injected at the 16-cell
      stage with a contrast agent, based on the gadolinium chelate gadolinium
      diethylenetriamine pentaacetic acid-dextran. The labeled progeny cells could be
      followed uniquely in three-dimensional magnetic resonance images, acquired from
      the embryo over several days. The results show that external ectodermal and
      internal mesodermal tissues extend at different rates during amphibian
      gastrulation and neurulation.

PMID- 7508144
TI  - [Pain connected to invasive techniques].

PMID- 7508145
TI  - [Treatment of chronic cancer pain. Contribution of acupuncture, auriculotherapy
      and mesotherapy].

PMID- 7508146
TI  - [The urodynamic examination in prostatism].
AB  - In a prospective study comprising 29 patients the authors analyzed
      comprehensively subjective complaints of prostatism using the score of prostatic
      symptoms (PSS) with the objective urodynamic finding (uroflowmetry, cystometry,
      pressure flow measurement) in men with benign prostatic hyperplasia. The Boyarsky
      and Madsen-Iversen PSS did not correlate with the infravesical obstruction
      assessed by the pressure flow measurements. An obstruction was detected in 23
      patients (79.3%), incl. a marginal one in 6 patients (20.7%), the diagnostic
      sensitivity of free uroflowmetry being 90.9%. Cystometry did not reveal a
      significant difference between the group with and without an obstruction,
      instability of the detrusor was found in 12 patients (41.4%) with a significant
      difference of the maximal cystometric capacity, as compared with the group of
      patients with a stable detrusor.

PMID- 7508148
TI  - Communicating with the aphasic dental patient.
AB  - A significant proportion of older adults has communication impairments. Language
      disorders involve problems with the use of learned symbol systems, including
      numbers, pictures, and words. Aphasia is one of the most common types of language
      disorders experienced by the elderly and is usually caused by a cerebrovascular
      accident or stroke, but can also be caused by head trauma and tumors. The growing
      number of dental patients with this language disorder will challenge the dental
      team to understand and evaluate aphasia and develop effective communication
      strategies. This paper describes the language impairments commonly experienced by
      stroke victims, and discusses assessment and communication strategies
      specifically for the aphasic dental patient.

PMID- 7508147
TI  - [Antiestrogens (tamoxifen) in the alternative therapy of benign prostatic
      hyperplasia].
AB  - In a non-randomized study the authors administered Tamoxifen to 17 patients with
      benign prostate hyperplasia who met the criteria for administration of the drug.
      In the group of patients no significant change of symptoms according to
      Goldenberg's score was recorded nor changes of prostate size and postmiction
      residues. In uroflowmetry the significant change of values of maximum flow (p <
      0.05) was not associated with a change in the mean flow. The authors assume that
      monotherapy with Tamoxifen is not effective enough and recommended administration
      of antioestrogen only in combination with other drugs.

PMID- 7508149
TI  - [HIV infections in children].

PMID- 7508150
TI  - Clinical teratology counseling and consultation case report: two distinct
      anterior neural tube defects in a human fetus: evidence for an intermittent
      pattern of neural tube closure.
AB  - Human neural tube closure is believed to be a continuous process that begins in
      the cervical region and progresses both rostrally and caudally. In contrast, an
      intermittent pattern of anterior neural tube closure has been demonstrated in
      rodents. Based on individual case photographs, a similar pattern of anterior
      neural tube closure, with multiple sites of closure, may also exist in humans. We
      report a human fetus with two distinct anterior neural tube defects separated by
      a cutaneous and mesenchymal bridge. The two defects occurred within distinct
      closure sites predicted by the murine model, one falling within closure II and
      the second within closure IV. Although one defect had adherent amniotic bands,
      evidence is presented to support a primary dysraphy rather than disruption from
      an amniotic band. This case provides further evidence supporting an intermittent
      pattern of anterior neural tube closure in human embryogenesis.

PMID- 7508151
TI  - Changes in dopamine, serotonin and their metabolites in discrete brain areas of
      rat offspring after in utero exposure to cocaine or related drugs.
AB  - The concentrations of dopamine (DA), serotonin (5HT) and their metabolites were
      quantified in 5 brain areas of rats exposed to saline, cocaine (15 mg/kg b.i.d.),
      amitriptyline (10 mg/kg), or amfonelic acid (AFA, 1.5 mg/kg) throughout
      gestation. Male pups from 3 similarly treated dams were fostered to 2 surrogate
      dams. The process of breeding and rearing was repeated 4 times with new dams to
      build the groups to 4-12, since only one pup per litter was used for any one
      measurement. AFA was used to mimic the dopamine (DA) uptake blockade and
      stimulant properties of cocaine and amitriptyline was used to mimic the other
      pharmacological effects of cocaine. At postnatal days (PND) 30, 60, and 180, one
      pup per litter was removed for HPLC analysis of monoamines. A second pup received
      0.3 mg/kg haloperidol, catalepsy assessed after 1 hr, and the brain used for
      analysis. The cataleptic response to haloperidol was unaffected by any prenatal
      treatment. The striatum from PND 30 cocaine rats had decreased levels of DA
      without a decrease in DA metabolites. At PND 60 in cocaine exposed rats, DA and
      DOPAC concentrations were increased, and 5HT levels were decreased in the
      striatum. The amitriptyline-exposed group exhibited decreased 5HT and 5-HIAA
      levels in the striatum. The hypothalamus of the cocaine group had lower levels of
      5-HIAA, and other brain areas had a trend for lower levels of 5HT and 5-HIAA. At
      PND 180, DOPAC was increased in the striatum and prefrontal cortex of the cocaine
      group. Haloperidol-induced altered monoamine metabolism was unaffected by any
      prenatal treatment at any age. These data suggest that age-related changes in the
      DA and 5HT neurotransmission systems occur in rats exposed prenatally to cocaine.
      However, the ability of the dopaminergic system to respond to a challenge by a DA
      receptor blocker is unaltered by these in utero treatments.

PMID- 7508152
TI  - Effect of unfragmented heparin alone and in combination with dextran on
      experimental venous thrombosis in rabbits.

PMID- 7508153
TI  - Heparin stimulates the proliferation of bovine aortic endothelial cells probably
      through activation of endogenous basic fibroblast growth factor.
AB  - We investigated the effect of heparin on the proliferation of cultured bovine
      aortic endothelial (BAE) cells. Heparin increased DNA synthesis in BAE cells in a
      concentration-dependent manner. The DNA synthesis increased by 2 to 2.5-fold with
      1 mg/ml of heparin after 48 h incubation without serum and exogenous fibroblast
      (heparin-binding) growth factors. The stimulating effect of heparin decreased
      with the diminishing number of monosaccharide units which constitute heparin. By
      the addition of a neutralizing antibody to basic fibroblast growth factor (bFGF),
      the stimulating effect of heparin decreased, whereas an antibody to acidic
      fibroblast growth factor (aFGF) had no effect. The culture medium conditioned by
      heparin-treated BAE cells stimulated DNA synthesis in Balb/3T3 fibroblasts that
      proliferate in response to bFGF. The mitogenic activity of the conditioned medium
      was suppressed by the antibody to bFGF. However, heparin did not increase bFGF
      mRNA level in BAE cells. These results suggest that heparin stimulates the
      proliferation of BAE cells by the activation of endogenous bFGF, but not by the
      induction of its synthesis.

PMID- 7508154
TI  - L-arginine infusion promotes nitric oxide-dependent vasodilation, increases
      regional cerebral blood flow, and reduces infarction volume in the rat.
AB  - BACKGROUND AND PURPOSE: We previously reported that L-arginine infusion increased
      pial vessel diameter by nitric oxide-dependent mechanisms, improved regional
      cerebral blood flow (rCBF) distal to middle cerebral artery (MCA) occlusion, and
      reduced infarction volume in spontaneously hypertensive rats when administered
      intraperitoneally before and after MCA occlusion. In this report we extend our
      findings (1) by examining the time course of L-arginine on rCBF and pial vessel
      diameter under basal conditions and on rCBF after MCA occlusion and (2) by
      reproducing the protective effect of L-arginine on infarct volume when given
      intravenously immediately after the onset of MCA occlusion in both normotensive
      and hypertensive models of focal cerebral ischemia. METHODS: Changes in pial
      vessel diameter (closed cranial window) and rCBF (laser-Doppler flowmetry) were
      measured over time after L-arginine infusion into anesthetized Sprague-Dawley
      rats. rCBF was also measured distal to MCA occlusion in a brain region showing
      rCBF reductions in the range of 80% of baseline. The effects of infusing L
      arginine (300 mg/kg for 10 minutes beginning 5 minutes after occlusion) were
      assessed on infarction volume in Sprague-Dawley rats after proximal MCA occlusion
      and in spontaneously hypertensive rats after common carotid artery plus distal
      MCA occlusion. RESULTS: L-Arginine (300 mg/kg IV) elevated rCBF by 20% when
      measured in the dorsolateral cortex of Sprague-Dawley rats and caused L
      nitroarginine-methyl ester-inhibitable increases in pial vessel diameter. L
      Arginine (> or = 30 mg/kg IV) increased blood flow distal to MCA occlusion by
      50%. These effects were sustained throughout the observation period (70 to 105
      minutes). Changes in mean arterial blood pressure were not observed. L-Arginine
      (300 mg/kg IV) reduced infarction volume by 35% and 28% in Sprague-Dawley and
      spontaneously hypertensive rats, respectively, when examined 24 hours after
      vessel occlusion. CONCLUSIONS: These studies extend our previous findings by
      demonstrating that exogenous L-arginine induces sustained rCBF increases in
      normal brain as well as in a marginally perfused brain region distal to MCA
      occlusion. Our data in Sprague-Dawley rats support the conclusion that L-arginine
      induced increases in rCBF can decrease infarction volume. We conclude that nitric
      oxide-mediated mechanisms increase rCBF and decrease infarction volume after MCA
      occlusion in both normotensive and hypertensive animals.

PMID- 7508156
TI  - Nitric oxide synthase inhibition alters cerebral blood flow and oxygen balance in
      focal cerebral ischemia in rats.
AB  - BACKGROUND AND PURPOSE: This study investigated whether the nitric oxide synthase
      inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) would alter blood flow and
      oxygen balance in the ischemic cerebrocortex of isoflurane-anesthetized Long
      Evans rats. METHODS: Fifteen minutes after middle cerebral artery occlusion, L
      NAME (1.5 mg/min per kilogram) was infused intravenously to the L-NAME group (n =
      14), and normal saline was given to the control group (n = 14) for 45 minutes. In
      each group, regional cerebral blood flow was determined with [14C]iodoantipyrine,
      and arterial and venous oxygen saturations were determined by
      microspectrophotometry. RESULTS: In both groups regional cerebral blood flow of
      the ischemic cortex was significantly lower than that of the contralateral cortex
      ([mean +/- SD] 55 +/- 13 versus 110 +/- 29 mL/min per 100 g in the control group
      and 35 +/- 13 versus 90 +/- 24 mL/min per 100 g in the L-NAME group). Compared
      with the blood flow in the ischemic cortex of the control group, L-NAME
      significantly reduced ischemic blood flow by 36%. Venous oxygen saturation was
      significantly increased in the ischemic cortex (41 +/- 1% versus 44 +/- 3%) but
      decreased in the contralateral cortex (65 +/- 3% versus 61 +/- 4%) by L-NAME.
      Calculated ischemic cortical oxygen consumption in the L-NAME group was 39% lower
      than that in the corresponding control group, whereas the difference was only 11%
      in the contralateral sides between groups. In both groups, the ratio of oxygen
      supply to consumption was lower in the ischemic than in the nonischemic regions.
      In the ischemic cortex, this ratio was significantly lower in the control group
      than in the L-NAME group (1.7 +/- 0.1 versus 1.9 +/- 0.1). In contrast, the ratio
      tended to be decreased by L-NAME in nonischemic regions. CONCLUSIONS: These
      observations suggest that despite a decrease in cerebral blood flow, inhibition
      of nitric oxide synthesis mildly improves the oxygen supply and consumption
      balance in the ischemic cortex.

PMID- 7508155
TI  - Nitric oxide inhibition aggravates ischemic damage of hippocampal but not of
      NADPH neurons in gerbils.
AB  - BACKGROUND AND PURPOSE: Nitric oxide may influence pathophysiology of brain
      ischemia in a complex way depending on the sources of its production either from
      neurons or endothelial cells. We investigated whether inhibition of nitric oxide
      synthesis affects postischemic neuronal death in hippocampus. Moreover, we
      evaluated whether the presence of nitric oxide synthase activity in specific
      neurons protects these against ischemia in the hippocampus, striatum, and
      sensorimotor cortex. METHODS: To inhibit nitric oxide synthase, several dosing
      regimens of NG-nitro-L-arginine methyl ester (L-NAME) were used (5 or 50 mg/kg
      IP, twice a day for 4 days, or 30 mg/kg IV) in gerbils. Control animals received
      either the isomer NG-nitro-D-arginine methyl ester or the vehicle. The gerbils
      underwent 10-minute occlusion of carotid arteries under ether anesthesia and
      controlled body temperature while physiological parameters were monitored.
      Neuronal damage was assessed 5 days after ischemia using Nissl-stained sections
      of hippocampus. Nitric oxide synthase neurons were histochemically stained for
      reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity.
      RESULTS: L-NAME treatments, but not the chronic one at 5 mg/kg, induced elevation
      of blood pressure (30% to 80% greater than the control level, P < .01), as
      observed shortly before and after bilateral carotid occlusion. Postischemic
      neuronal loss in the CA1 through CA4 sectors was worsened by chronic pretreatment
      with L-NAME at 50 mg/kg (eg, CA1 neuronal counts per 100-microns length: 3.2 +/-
      2.74, mean +/- SD; n = 19; P < .01). After the acute (30 mg/kg) or chronic
      pretreatment at lower dosage (5 mg/kg) with L-NAME, neuronal loss was comparable
      to that of animals treated with the D-isomer or the vehicle (CA1 counts in
      vehicle-treated animals: 7.65 +/- 6.51, mean +/- SD; n = 14). None of the L-NAME
      treatments affected postischemic survival of NADPH diaphorase-positive neurons in
      hippocampus, striatum, and sensorimotor cortex. CONCLUSIONS: These observations
      demonstrate that inhibition of endothelial and neuronal nitric oxide synthase
      activity does not modify resistance of nitric oxide-producing neurons to
      transient ischemia. The severe inhibition of nitric oxide production aggravates
      postischemic neuronal death in the hippocampus, whereas the mild inhibition is
      ineffective.

PMID- 7508157
TI  - Untransfected and SV40-transfected fetal and postnatal human thymic stromal
      cells. Analysis of phenotype, cytokine gene expression and cytokine production.
AB  - The thymic stromal network is complex and heterogeneous, containing thymic
      epithelial cells which are thought to play an important role during T-cell
      development and thymic fibroblasts which role is less defined. We herein present
      a phenotypic and functional comparison between defined thymic stromal cell
      populations. We transfected SV40 ori- into fetal and postnatal thymic stromal
      cell cultures and obtained SV40-immortalized clones of epithelial and
      fibroblastic nature as demonstrated by expression of intracellular keratin. These
      various clones were characterized in detail and compared to their untransfected
      bulk culture counterparts for phenotype, cytokine gene expression and cytokine
      production. All the different thymic stromal cells examined, constitutively
      expressed ICAM-1, LFA-3, MHC class I antigens, CD44, and the genes coding for IL
      7, SCF and TGF-beta, but not TNF-alpha. After IL-1 stimulation, epithelial cells
      seemed to produce more GM-CSF than fibroblasts, and that trend was also seen for
      IL-6 secretion. SV40 cells were also regulated by IFN-gamma which induced MHC
      class II antigens and inhibited the IL-1 induced GM-CSF production. SV40 cells
      differed from their untransfected counterparts by an atypical expression of CD40
      and lacked constitutive IL-1 alpha gene expression. We isolated clones with
      distinct properties, 24SV48, a highly proliferative CD34 positive TEC secreting
      low levels of GM-CSF and lacking constitutive IL-1 alpha and beta gene
      expression, and CT1SV93, an epithelial clone of postnatal origin with a high IL-1
      induced cytokine production. In spite of differences with untransfected bulk
      cultures, the various SV40 immortalized clones may represent useful tools to
      further study the human thymic stroma.

PMID- 7508159
TI  - Cardiovascular disease mortality in the Americas.
AB  - Despite subregional differences, mortality profiles have undergone major changes
      in most countries of the Americas. While the proportion of deaths caused by
      noncommunicable diseases, particularly cardiovascular diseases, has increased,
      overall age-adjusted mortality rates attributable to all cardiovascular disease
      are declining in 13 of the 15 countries selected for the present study. About
      half the countries showed decreasing mortality rates for ischaemic heart disease;
      the other half had increasing rates. The mortality rates for cerebrovascular
      disease and hypertensive disease declined in all but four countries. The
      ischaemic heart disease/cerebrovascular disease mortality ratio increased as a
      consequence of a greater decline in deaths due to cerebrovascular disease, except
      in two countries that exhibited a greater decline for ischaemic heart disease.
      With few exceptions the male-to-female mortality ratios increased for all
      cardiovascular disease, ischaemic heart disease and cerebrovascular disease,
      reflecting a greater decline in female mortality. In general there was a decline
      in all cardiovascular disease mortality for almost every age group in the North
      American, Southern Cone, English-speaking Caribbean, and Andean subregions, while
      there were increases in the Central American and Latin Caribbean subregions. The
      magnitude of the changes was related to the initial level of mortality and the
      date of onset of the decline. Change began earlier and the declines were largest
      in the countries with the highest initial mortality levels, whereas in the
      countries that initially had comparatively low values the mortality rates are
      still increasing. Insufficient information is available to permit elucidation of
      the determinants of the changes reported. There has been speculation about the
      possible role of factors such as demographic and sociocultural changes, changes
      in lifestyle and subsequently in the prevalence of risk factors for
      cardiovascular disease, and the increased utilization of advanced diagnostic and
      therapeutic technologies.

PMID- 7508160
TI  - [Overtreatment in advanced tumors of the head and neck].
AB  - So-called "over-treatment" in the practical management of advanced head and neck
      tumors is a very important problem in terms of its professional, ethical, moral
      and legal implications, that involve the physician in the therapeutic decision he
      must make. After presenting the general aspects of the subject, the chairman,
      together with all those participating in the Round Table, deals with the most
      important points of the problem: the definition of overtreatment, the limits of
      treatment, nontreatment, passive euthanasia, informed consent and quality of
      life. The various aspects of the problem have been dealt with and discussed from
      the point of view of the surgeon, the expert in bio-ethics and the magistrate.
      After comparing the different opinions, the most important point, in terms of a
      therapeutic choice, should be the patient's quality of life, whose improvement
      justifies every therapeutic strategy. Given that the advances in surgery, either
      demolitive or above all reconstructive, have made almost every operation
      technically possible, attention has been concentrated on overtreatment in
      nonsurgical therapies. In extremely advanced tumors, radio- and chemotherapy are
      often burdened by side effects and sequelae that lead to a quality of life at the
      limits of biological supportability. The Round Table ends with the presentation
      of emblematic case reports, followed by a vivacious discussion, also with those
      in the audience, that was basically in agreement with the therapeutic choices
      made.

PMID- 7508158
TI  - [The assessment of the interferon status of term newborns born to mothers with
      chronic nonspecific lung diseases].
AB  - The study involved 34 full-term newborn babies born by mothers with chronic
      nonspecific diseases of the lungs and 10 newborns born by mothers with the
      physiological course of pregnancy and parturition, the examinations being carried
      out in the early neonatal period. A lower capacity for production of endogenous
      and gamma-interferons at delivery and on day 6 of life as well as a higher
      incidence of intrauterine and postnatal infections were observed in the newborns
      of the first group. This indicated the necessity to consider such babies as a
      group at risk of developing neonatal complications. The data of the study may be
      used for early diagnosis and prognosis of perinatal infections.

PMID- 7508162
TI  - Interferon-gamma and kit ligand are primary regulators of GTP cyclohydrolase
      activity: mechanisms and implications.

PMID- 7508161
TI  - Pathological characteristics of surgically removed craniopharyngiomas: analysis
      of 131 cases.
AB  - Pathological specimens of 131 surgically removed craniopharyngiomas were obtained
      from the registry of the National Institute of Neurosurgery, Budapest between
      1977 and 1991. The cases were reviewed statistically with reference to their
      gross and microscopic features and clinical characteristics. Macroscopically, 34%
      of the tumours were cystic, 23% solid and 43% mixed. Histologically, 38% of the
      cases belonged to the adamantinous group, 26% were squamous epithelial type, 15%
      were combined, that is expressing the characteristics of both. In 21% of the
      cases the surgically removed samples did not contain enough material for correct
      histopathologic classification. There was no recurrence in the group with the
      squamous epithelial type tumours, while 59% of the adamantinous, and 36% of the
      combined craniopharyngiomas recurred. The 5-year survival proportion was 73% at
      the squamous epithelial, 60% in the adamantinous, and 55% at the combined
      histological types.

PMID- 7508164
TI  - Nitric oxide synthase: function and mechanism.

PMID- 7508163
TI  - Tetrahydrobiopterin deficiency in Portugal: results of the screening for
      hyperphenylalaninemia.

PMID- 7508165
TI  - Macrophage nitric oxide synthase: tetrahydrobiopterin decreases the NADPH
      stoichiometry.

PMID- 7508169
TI  - Modulation of nitric oxide synthase activity in intact cells by intracellular
      tetrahydrobiopterin levels.

PMID- 7508167
TI  - 6R-[3H]tetrahydrobiopterin binding activities in rat brain.

PMID- 7508166
TI  - Tetrahydrobiopterin synthesis is induced by LPS in vascular smooth muscle and is
      rate-limiting for nitric oxide production.
AB  - GTPCH1 mRNA and BH4 synthesis is increased by LPS in vascular smooth muscle. Our
      data suggest that induction of GTPCH1 and NOS represent two arms of a common
      pathway required for immunostimulant-evoked NO synthesis. This conclusion is
      consistent with the view that the major function of immunostimulant-evoked BH4 is
      to support NOS. Moreover, GTPCH1 and other enzymes of the de novo BH4 synthetic
      pathway may prove to be important targets for therapy of clinical conditions
      arising from NO overproduction. As we begin to reveal the molecular events
      governing the induction and expression of GTPCH1 and NOS, additional therapeutic
      approaches for treating NO overproduction are certain to be revealed.

PMID- 7508168
TI  - Inducible nitric oxide synthase activity in hepatocytes is dependent on the
      coinduction of tetrahydrobiopterin synthesis.

PMID- 7508170
TI  - Evaluation of immunohistochemical staining and activity of thymidylate synthase
      in cell lines.

PMID- 7508171
TI  - Increased activity of gamma-glutamyl hydrolase in human sarcoma cell lines: a
      novel mechanism of intrinsic resistance to methotrexate (MTX).

PMID- 7508172
TI  - Mechanism-based approaches to inhibition of the synthesis and degradation of
      folate and antifolate polyglutamates.

PMID- 7508173
TI  - Metabolism of folate glutamates in Aspergillus nidulans.

PMID- 7508174
TI  - The kit ligand, stem cell factor.

PMID- 7508175
TI  - CD5 B cells, a fetal B cell lineage.

PMID- 7508176
TI  - Human natural killer cells: origin, clonality, specificity, and receptors.

PMID- 7508177
TI  - The immune system of mice lacking conventional MHC class II molecules.

PMID- 7508178
TI  - Effects of dexamethasone in a model of lung hyperresponsiveness in the rat.
AB  - In rats, Sephadex treatment on days 0, 2 and either 4 or 5 resulted in a blood
      and lung eosinophilia, an increase in lung cell fragility, an increase in the
      functional activity of peritoneal eosinophils in vitro and a sustained increased
      responsiveness of lung parenchymal strips to KCl, 5-hydroxytryptamine (5-HT) and
      carbachol that was not associated with oedema or gross fibrosis. The
      corticosteroid dexamethasone, when given before each injection of Sephadex,
      reduced all these effects of Sephadex. When given 30 min after the last injection
      of Sephadex, dexamethasone had no effect on the number of blood and lung
      eosinophils but it did reduce the functional activity of peritoneal eosinophils,
      the increased lung cell fragility and the hyperresponsiveness to 5-HT. Repeated
      administration of dexamethasone to rats with an established hyperresponsiveness
      that was no longer associated with cellular inflammation had minimal effects on
      this hyperresponsiveness.

PMID- 7508180
TI  - Care of the cancer patient.

PMID- 7508179
TI  - HRF of 30 kDa: evidence for active synthesis.
AB  - A variety of mediators are involved in the pathophysiology of a number of
      clinical conditions. Among them histamine-releasing factors (HRF) act as
      secretagogue for basophils and mast cells to cause cell degranulation and
      histamine release. Studies on the kinetics of HRF production by activated
      mononuclear cells (MNC) have suggested an active synthesis of this cytokine.
      Using a [35S]-metabolic cell labeling method, we first analyzed the capacity of
      MNC from patients with allergic rhinitis to ragweed to actively synthesize HRF.
      We then found that stimulation of MNC with allergen promoted a synthesis of large
      quantities of proteins, including a protein of about 30 kDa. Secondly, we
      developed a method for the enrichment of HRF molecules from crude supernatants of
      ragweed-stimulated MNC using ion exchange and gel filtration chromatography. We
      observed that the yield of HRF activity is seen just before the chymotrypsinogen
      marker. The estimated molecular weight was 30-35 kDa.

PMID- 7508076
TI  - Functions of the gene products of Escherichia coli.
AB  - A list of currently identified gene products of Escherichia coli is given,
      together with a bibliography that provides pointers to the literature on each
      gene product. A scheme to categorize cellular functions is used to classify the
      gene products of E. coli so far identified. A count shows that the numbers of
      genes concerned with small-molecule metabolism are on the same order as the
      numbers concerned with macromolecule biosynthesis and degradation. One large
      category is the category of tRNAs and their synthetases. Another is the category
      of transport elements. The categories of cell structure and cellular processes
      other than metabolism are smaller. Other subjects discussed are the occurrence in
      the E. coli genome of redundant pairs and groups of genes of identical or closely
      similar function, as well as variation in the degree of density of genetic
      information in different parts of the genome.

PMID- 7508181
TI  - Preferential sites in keratin 10 that are mutated in epidermolytic
      hyperkeratosis.
AB  - Epidermolytic hyperkeratosis (EH) is a rare autosomal dominant skin disease.
      Recent studies in our laboratory established genetic linkage to the type II
      keratin gene locus on chromosome 12q in one family with EH and identified a
      single amino acid mutation in keratin 1 that is responsible for the disease.
      Other point mutations in the keratin 1 or keratin 10 genes have now been reported
      in other patients with EH. We have examined a series of probands with EH in order
      to develop a catalog of mutations in keratin 10. Using direct sequencing of PCR
      amplified genomic DNA, we have identified mutations in six families, in which
      five mutations occur in the beginning of the 1A rod domain of keratin 10-namely,
      two ARg10 to His, one Arg10 to Cys, and Asn8 to His, and a Tyr14 to Asp. This
      region contains highly conserved residues among all keratins. An additional
      mutation (Leu103 to Gln) was found in the conserved region late in the 2B rod
      domain in keratin 10. We developed several allele-specific assays to assess the
      frequency of these mutations in the general population. No evidence was found for
      the presence of such changes in unaffected individuals. In vitro functional
      assays performed with peptides corresponding to the 1A mutations in these
      families show severely diminished capacity to disaggregate preformed keratin
      intermediate filaments, in comparison with a wild-type control peptide. Results
      from this work support the hypothesis that the beginning of the 1A rod domain
      segment in keratin 10 contains preferential sites for disease-causing mutation in
      EH. This should be of considerable use when developing prenatal diagnostic tests
      and biologically based therapies for this disease.

PMID- 7508183
TI  - A healthy male with compound and double heterozygosities for delta F508, F508C,
      and M47OV in exon 10 of the cystic fibrosis gene.

PMID- 7508182
TI  - Detection of a major gene for heterocellular hereditary persistence of fetal
      hemoglobin after accounting for genetic modifiers.
AB  - "Heterocellular hereditary persistence of fetal hemoglobin" (HPFH) is the term
      used to describe the genetically determined persistence of fetal hemoglobin (Hb
      F) production into adult life, in the absence of any related hematological
      disorder. Whereas some forms are caused by mutations in the beta-globin gene
      cluster on chromosome 11, others segregate independently. While the latter are of
      particular interest with respect to the regulation of globin gene switching, it
      has not been possible to determine their chromosomal location, mainly because
      their mode of inheritance is not clear, but also because several other factors
      are known to modify Hb F production. We have examined a large Asian Indian
      pedigree which includes individuals with heterocellular HPFH associated with beta
      thalassemia and/or alpha-thalassemia. Segregation analysis was conducted on the
      HPFH trait FC, defined to be the percentage of Hb F-containing cells (F-cells),
      using the class D regressive model. Our results provide evidence for the presence
      of a major gene, dominant or codominant, which controls the FC values with
      residual familial correlations. The major gene was detected when the effects of
      genetic modifiers, notably beta-thalassemia and the XmnI-G gamma polymorphism,
      are accounted for in the analysis. Linkage with the beta-globin gene cluster is
      excluded. The transmission of the FC values in this pedigree is informative
      enough to allow detection of linkage with an appropriate marker(s). The
      analytical approach outlined in this study, using simple regression to allow for
      genetic modifiers and thus allowing the mode of inheritance of a trait to be
      dissected out, may be useful as a model for segregation and linkage analyses of
      other complex phenotypes.

PMID- 7508184
TI  - Cl- regulation of a Ca(2+)-activated nonselective cation channel in beta-agonist
      treated fetal distal lung epithelium.
AB  - Nonselective cation (NSC) channels have been identified in the apical membrane of
      fetal distal lung epithelium (FDLE). However, their physiological role in Na+
      transport is uncertain. Because terbutaline, a beta 2-agonist, increases Na+
      transport by FDLE, we studied its effect and selected signal transduction
      mechanisms on NSC channel activity. Using patch-clamp and single-cell imaging
      techniques, we found that terbutaline activated the NSC channel by 1) increasing
      its sensitivity to cytosolic Ca2+ concentration ([Ca2+]c) by 100- to 1,000-fold,
      2) increasing [Ca2+]c from 35 nM to 3.3 microM, 3) producing a dependency of the
      NSC channel activity on the cytosolic Cl- concentration ([Cl-]c) at a
      physiological [Ca2+]c, and 4) inducing a reduction in the [Cl-]c from 45 to 25
      mM, which directly activates the beta 2-treated NSC channel. These observations
      indicate that a beta 2-agonist physiologically activates an amiloride-blockable
      NSC channel in FDLE through an increase in its sensitivity to [Ca2+]c, resulting
      in the development of a [Cl-]c dependency at a physiological [Ca2+]c associated
      with both an increase in [Ca2+]c and a reduction in [Cl-]c. A development of the
      [Cl-]c dependency and a reduction in [Cl-]c act as a second messenger of the beta
      agonist signal transduction pathway in this Na(+)-transporting epithelium.

PMID- 7508185
TI  - Effects of orchiectomy on EDL muscle ultrastructure and energy-supplying enzymes
      in growing male guinea pigs.
AB  - To investigate the influence of androgens on muscle maturation during growth,
      guinea pigs were orchiectomized (CX) or sham operated (SO) at the end of weaning.
      Extensor digitorum longus (EDL) muscles were removed at weeks 4, 8, and 12 of
      postnatal development. According to their contractile and metabolic
      characteristics, four fiber types were distinguished, called I, IIa, IIbox, and
      IIbglyc. Muscle maturation consisted of a concomitant decrease in percentages of
      type IIa and IIbglyc fibers and increase in the percentage of IIbox fibers in
      both groups. At week 12, fiber distributions were not different between the two
      groups. Citrate synthase activity fell and phosphofructokinase and lactate
      dehydrogenase (LDH) activities rose from week 4 to week 12 and were the same in
      CX and SO. Muscular LDH subunits increased in SO and decreased in CX during this
      period. In conclusion, fiber type distribution and enzyme activities at puberty
      were not androgen dependent in guinea pig EDL muscle. Conversely, these hormones
      acted on LDH isozyme distribution through the enhancement of the most glycolytic
      LDH fractions.

PMID- 7508187
TI  - Expression, functional analysis, and in situ hybridization of a cloned rat kidney
      collecting duct water channel.
AB  - The cloning and expression of an apical membrane water channel from rat kidney
      collecting duct (WCH-CD) homologous to a 28-kDa integral membrane protein
      (CHIP28) was reported recently (K. Fushimi, S. Uchida, Y. Hara, Y. Hirata, F.
      Marumo, and S. Sasaki. Nature Lond. 361: 549-552, 1993). We obtained an
      approximately 1.8-kilobase clone from a rat kidney lambda gt10 cDNA library by a
      polymerase chain reaction cloning method; whereas the coding sequence (814 base
      pairs, predicted protein size 29 kDa) was identical to that reported, we
      identified an in-frame ATG codon at base pair -123 predicting a protein size of
      33 kDa. On Northern blots probed by cDNAs corresponding to the WCH-CD coding
      sequence (base pairs +1 to +814) or 5'-untranslated sequence (-403 to -16), a
      single band at 1.9 kilobases was observed in kidney medulla greater than in
      cortex but not in other tissues; mRNA expression was increased strongly by
      dehydration. Translation and oocyte expression studies were performed to identify
      the translation start site. The short (base pairs +1 to +814) and long (base
      pairs -123 to +814) cDNAs were subcloned in vector pSP64 containing the 5'
      untranslated Xenopus globin sequence upstream to the ATGs; a 30-base pair c-myc
      sequence was engineered at the COOH- terminal for antibody recognition.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7508186
TI  - Functional CFTR in endosomal compartment of CFTR-expressing fibroblasts and T84
      cells.
AB  - It was proposed that the cystic fibrosis transmembrane conductance regulator
      (CFTR) functions in the endosomal compartment as a adenosine 3',5'-cyclic
      monophosphate (cAMP)-regulated Cl channel that regulates endosomal acidification
      (J. Barasch, B. Kiss, A. Prince, L. Saiman, D. Gruenert, and A. Al-Awqati, Nature
      Lond. 352: 70-73, 1991). This hypothesis was tested in stably transfected Swiss
      3T3 fibroblasts expressing CFTR or delta F508 CFTR and in T84 epithelial cells
      that normally express CFTR. In fibroblasts, the time course of pH in individual
      endosomes was measured by quantitative image analysis after 1 min pulse labeling
      with 2 microM carboxyfluorescein (Cf)-tetramethylrhodamine-transferrin (K. Zen,
      J. Biwersi, N. Periasamy, and A. S. Verkman. J. Cell Biol. 119: 99-110, 1992).
      Average endosomal pH reached 6.20 +/- 0.07 (SE) after 15 min in the mock
      transfected cells with a half time of approximately 3 min; pH was slightly lower
      (5.97 +/- 0.06) in the CFTR-expressing fibroblasts. The difference did not result
      from a subpopulation of highly acidic endosomes. Forskolin (10 microM) increased
      average pH to 6.62 +/- 0.03 and abolished the difference. For determination of Cl
      conductance, endosomes in fibroblasts and T84 cells were labeled with Cf-dextran
      (5 mg/ml); dissipation of the endosomal pH gradient was measured in response to
      rapid addition of the protonophore carbonyl cyanide m-chlorophenylhydrazone
      (CCCP; 20 microM). Because the proton flux across the endosomal membrane is
      limited by the movement of K and Cl, the rate of alkalinization (dpH/dt) after
      CCCP addition provided a measure of endosomal Cl conductance. In CFTR-expressing
      fibroblasts, forskolin (10 microM) increased dpH/dt 1.6 +/- 0.2-fold (n =
      14).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508188
TI  - CFTR and calcium-activated chloride currents in pancreatic duct cells of a
      transgenic CF mouse.
AB  - We have studied the cystic fibrosis transmembrane conductance regulator (CFTR)
      and calcium-activated chloride currents in pancreatic duct cells isolated from a
      transgenic cf/cf mouse created by targeted insertional mutagenesis. Adenosine
      3',5'-cyclic monophosphate (cAMP)-activated CFTR chloride currents were detected
      in 78% (29/37) of wild-type cells, in 81% (35/43) of heterozygote cells, and in
      61% (29/47) of homozygous cf/cf duct cells (P > 0.05, cf/cf vs. wild-type and
      heterozygote). The CFTR current density measured at membrane potentials of +/- 60
      mV averaged 22-26 pA/pF in wild-type and heterozygote groups but only 13 pA/pF in
      cells derived from cf/cf animals (P < 0.05, cf/cf vs. wild-type and cf/cf vs.
      heterozygotes). In contrast, duct cells from animals of all three genotypic
      groups exhibited calcium-activated chloride currents that were of similar
      magnitude and up to 11-fold larger than the CFTR currents. We speculate that
      these transgenic insertional null mice do not develop the pancreatic pathology
      that occurs in cystic fibrosis patients because their duct cells contain 1) some
      wild-type CFTR generated by exon skipping and aberrant splicing and 2) a separate
      anion secretory pathway mediated by calcium-activated chloride channels.

PMID- 7508189
TI  - Identification of an endothelial-like type III NO synthase in LLC-PK1 kidney
      epithelial cells.
AB  - Porcine kidney tubular epithelial cells (LLC-PK1) produce nitric oxide or a
      related compound (e.g., a nitrosothiol) after stimulation with various agonists.
      We now report the identification and characterization of a constitutive,
      particulate nitric oxide (NO) synthase from LLC-PK1 cells. After partial
      purification on adenosine 2',5'-bisphosphate-Sepharose, the particulate NO
      synthase activity eluted anomalously from Superose 6 gel permeation columns near
      the total included volume, similar to that observed for the endothelial (type
      III) NO synthase. Substrate/cofactor requirements of the epithelial and
      endothelial NO synthases were identical, i.e., dependency on L-arginine, (6R)
      5,6,7,8-tetrahydrobiopterin, FAD, calcium and calmodulin. The epithelial enzyme
      activity was inhibited by the arginine analogues, NG-methyl-L-arginine (100
      microM) and NG-nitro-L-arginine (100 microM), as well as the calmodulin
      antagonists, trifluoperazine (100 microM) and calmidazolium (30 microM). Anti
      type III (H32), but not anti-type I (brain, 6763-5) or anti-type II (macrophage,
      8196) NO synthase antibodies, detected a single immunoreactive band in the LLC
      PK1 particulate fraction of approximately 140 kDa by Western blot analysis.
      Finally, the presence of type III NO synthase mRNA in LLC-PK1 cells was
      demonstrated using the polymerase chain reaction. These data indicate that LLC
      PK1 kidney epithelial cells contain type III NO synthase, which has been
      classically associated with the vascular endothelium.

PMID- 7508190
TI  - Polarization-dependent apical membrane CFTR targeting underlies cAMP-stimulated
      Cl- secretion in epithelial cells.
AB  - The relationship between adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl-
      secretion and the cellular location of the cystic fibrosis transmembrane
      conductance regulator (CFTR) was determined in both polarized (Cl.19A) and
      unpolarized (parental) HT-29 colonocytes expressing similar levels of CFTR mRNA
      and protein. CFTR immunolocalized to the apical membrane domain of polarized
      colonocytes exhibiting cAMP-responsive Cl- secretion. In contrast, CFTR staining
      was perinuclear in unpolarized colonocytes, which gave little or no cAMP
      stimulated Cl- conductance responses. Thus cAMP-stimulated Cl- secretion
      coincided with an apical localization of CFTR. Brefeldin A (BFA) was used to
      perturb glycoprotein targeting in these cells. In polarized colonocytes, BFA
      caused a reversible, time-dependent decrease in the Cl-conductance response to
      cAMP but not Ca2+. Apical CFTR redistributed into large coalesced intracellular
      vesicles, located within the same plane as the microtubule organizing center, a
      marker for the trans-Golgi network (TGN). In preconfluent monolayers or
      unpolarized HT-29 cells, BFA had no effect on CFTR staining, which remained
      perinuclear. Mature, Golgi-processed CFTR protein was isolated from both
      polarized and unpolarized colonocytes. Thus the mechanism for polarization
      dependent apical membrane CFTR targeting and the acquisition of cAMP-dependent Cl
      secretion lies at or beyond the late Golgi-TGN in epithelial cells.

PMID- 7508191
TI  - Dihydropyridine-sensitive initial component of the ANG II-induced Ca2+ response
      in rat adrenal glomerulosa cells.
AB  - The Ca2+ signal induced by an increase in extracellular K+ concentration from 3.6
      to 5.6 mM or angiotensin II (ANG II) was inhibited by the dihydropyridine (DHP)
      Ca2+ channel blocker, nifedipine, and enhanced by the DHP Ca2+ channel agonist,
      BAY K 8644. The DHP sensitivity of the ANG II-induced Ca2+ response was already
      detectable during the peak phase, suggesting that the DHP receptor plays an
      important role during the initial phase of ANG II stimulation. K+ and ANG II
      stimulated a nifedipine-sensitive Mn2+ influx pathway, further promoting the role
      of a DHP receptor in their mechanism of action. Fluorescent membrane potential
      measurements showed that, in contrast to the rapid depolarization induced by K+,
      the ANG II-induced depolarization had a lag time of > 30 s. The slow kinetics of
      depolarization compared with the immediate effect of ANG II on Mn2+ influx and
      the DHP sensitivity of the initial Ca2+ peak indicates that ANG II initiates the
      activation of the DHP-sensitive Ca2+ channel by a mechanism other than
      depolarization.

PMID- 7508192
TI  - Insulin-like growth factor and growth hormone receptor in nephrotic rats.
AB  - In an attempt to elucidate the mechanism of growth retardation in the nephrotic
      syndrome, specific serum and hepatic growth factors were measured in Sprague
      Dawley rats in which nephrotic syndrome was produced by administration of
      puromycin (1.5 mg.100 g body wt-1.day-1) for 12 days. On the 13th day, the
      results of these nephrotic animals were compared with those of an equal number of
      pair-fed and control animals: the mean dietary intake of the nephrotic group was
      71% that of the control group (P < 0.001). Serum insulin-like growth factor (IGF)
      binding protein-3 was significantly reduced (P < 0.005) in the nephrotic rats,
      compared with the pair-fed and the control groups. Hepatic IGF-I mRNA in the
      nephrotic rats averaged 36% that of control (P < 0.001) and 46% that of the pair
      fed animals (P < 0.001). Hepatic growth hormone receptor (GHr) mRNA in the
      nephrotic rats averaged 19% of that of the control (P < 0.001) and 27% of that of
      the pair-fed rats (P < 0.001). These results indicate that the growth retardation
      of the nephrotic rats may be associated with the significant decrease in IGF-I
      mRNA and reduction in GHr mRNA.

PMID- 7508193
TI  - Effect of growth hormone administration and treadmill exercise on serum and
      skeletal IGF-I in rats.
AB  - Growth factors may be mediators of local and systemic factors that enhance bone
      formation. This study examined the effect of treadmill exercise and ovine growth
      hormone administration on levels of insulin-like growth factor I (IGF-I) in serum
      (ng/ml), long bone, and vertebrae and on bone formation rate. Forty female rats
      were divided into four groups: control; exercise (17 m/min, 1 h/day); growth
      hormone (0.05 mg.100 g-1.day-1); growth hormone plus exercise. After 9 wk of
      study, the serum levels of IGF-I were higher in the intervention groups than in
      the control group; however, the IGF-I concentration and the periosteal bone
      formation rate in the long bone were significantly higher only in the exercised
      rats. The IGF-I concentration and the cancellous bone formation rate in the
      vertebrae did not differ among the experimental groups. The vertebral and long
      bone formation rate were correlated with bone concentrations of IGF-I. Serum
      levels of IGF-I were also correlated with serum osteocalcin and the long bone
      formation but not with the vertebral bone formation. The association of bone
      formation with serum and bone IGF-I supports the suggestion that IGF-I is one of
      the growth factors that regulate bone formation, in particular as a mediator of
      the response of bone to exercise.

PMID- 7508194
TI  - Physiological role of galanin in the regulation of anterior pituitary function in
      humans.
AB  - The aim of our study was to elucidate the physiological role of the neuropeptide
      galanin in the regulation of anterior pituitary function in human subjects. Six
      healthy men (age range 26-35 yr, body mass index range 20-24 kg/m2) underwent in
      random order 1) an intravenous bolus injection of growth hormone-releasing
      hormone (GHRH)-(1-29)-NH2 (100 micrograms) + thyrotropin-releasing hormone (TRH,
      200 micrograms) + luteinizing hormone-releasing hormone (LHRH, 100 micrograms) +
      corticotropin-releasing hormone (CRH, 100 micrograms), and 2) intravenous saline
      (100 ml) at time 0 plus either human galanin (500 micrograms) in saline (100 ml)
      or saline (100 ml) from -15 to +30 min. Human galanin determined a significant
      increase in serum GH (GH peak: 11.3 +/- 2.2 micrograms/l) from both baseline and
      placebo levels. No significant differences were observed between GH values after
      galanin and those after GHRH alone (24.3 +/- 5.2 micrograms/l). Human galanin
      significantly enhanced the GH response to GHRH (peak 49.5 +/- 10 micrograms/l)
      with respect to either GHRH or galanin alone. Human galanin caused a slight
      decrease in baseline serum adrenocorticotropic hormone (ACTH; 16.3 +/- 2.4 pg/ml)
      and cortisol levels (8 +/- 1.5 micrograms/dl). Galanin also determined a slight
      reduction in both the ACTH (peak 27 +/- 8 pg/ml) and cortisol (peak 13.8 +/- 1.3
      micrograms/dl) responses to CRH. Baseline and releasing hormone-stimulated
      secretions of prolactin, thyroid-stimulating hormone, LH, and follicle
      stimulating hormone were not altered by galanin. Our data suggest a physiological
      role for the neuropeptide galanin in the regulation of GH secretion in
      humans.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508195
TI  - Interleukin-1 increases protein kinase A activity by a cAMP-independent mechanism
      in AtT-20 cells.
AB  - A recent study from this laboratory has shown that the inflammatory mediator,
      interleukin-1 alpha (IL-1 alpha), stimulates protein kinase A (PKA) activity and
      adrenocorticotropic hormone (ACTH) secretion from AtT-20 cells without any
      detectable increase in intracellular cAMP accumulation. The present studies were
      conducted to determine if cAMP is involved in IL-1 alpha activation of PKA and if
      PKA is responsible for IL-1 alpha-induced ACTH release from AtT-20 cells. The
      data are consistent with a novel mechanism of PKA activation that does not
      involve cAMP. Inhibition of adenylate cyclase with 2'5'-dideoxyadenosine (2'5'
      DDA) did not affect IL-1 alpha-induced increases in PKA activity and ACTH
      secretion. In contrast, CRF-stimulated PKA activity and ACTH secretion were
      inhibited by 2'5'-DDA. Additional evidence was obtained using the
      phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). IBMX did not
      alter IL-1 alpha-induced PKA activity or ACTH secretion, yet IBMX potentiated CRF
      induced cAMP accumulation. Inhibition of PKA with the PKA inhibitor, H-8, blocked
      activation of PKA and ACTH secretion by both IL-1 alpha and CRF in AtT-20 cells.
      These observations demonstrate that 1) the mechanism of IL-1 alpha activation of
      PKA is independent of adenylate cyclase or cAMP and 2) PKA is used by IL-1 alpha
      to induce ACTH secretion from AtT-20 cells.

PMID- 7508196
TI  - Characterization of galanin receptor in canine small intestinal circular muscle
      synaptosomes.
AB  - We used 125I-galanin (porcine) as ligand to study the galanin receptors in
      circular muscle and deep muscular plexus from canine small intestine. Specific
      binding sites were found in both nerve and muscle membranes. On synaptosomal
      membranes, the equilibrium binding study showed a high-affinity (dissociation
      constant, Kd = 1.1 +/- 0.13 nM; maximum binding capacity, Bmax = 244 +/- 2.1
      fmol/mg) binding site. The specific binding of 125I-galanin to nerve membrane was
      inhibited by galanin or NH2-terminal galanin fragments but not by the COOH
      terminal fragment. Computer analysis suggested a two-site model (inhibitor
      constants, Ki1 = 0.02 +/- 0.005 nM and Ki2 = 1.05 +/- 0.3 nM) for competition by
      galanin-(1-29). Kinetic and competition studies using guanosine 5'-O-(3
      thiotriphosphate) or pertussis toxin (PTX) suggested that the high-affinity
      binding site involved a PTX-sensitive G protein which acted to slow dissociation
      of bound galanin from the receptor. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis of the galanin receptor complex revealed a radioactive
      band at 50 kDa. We conclude that, in canine small intestine, galanin may act as
      an inhibitory neuromodulator by a PTX-sensitive G protein-coupled interaction of
      galanin and its specific receptor on enteric nerve synaptosomes.

PMID- 7508197
TI  - Galanin receptor in plasma membrane of canine small intestinal circular muscle.
AB  - High-affinity binding sites for galanin were identified and characterized in
      plasma membrane of circular muscle from canine small intestine using 125I
      radioiodinated synthetic porcine galanin. Scatchard analysis indicated a high
      affinity binding site on plasma membrane with a dissociation constant (Kd) of
      0.58 nM and a binding capacity of 389 fmol/mg. Unlabeled galanin or NH2-terminal
      galanin fragments competitively inhibited the binding of 125I-galanin in a
      concentration-dependent manner, whereas the COOH-terminal fragment was inactive.
      Computer analysis of competitive binding data suggested a two-site model with a
      high-affinity (inhibitor constant, Ki = 0.01 nM) and a low-affinity (Ki = 2.8 nM)
      binding site. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) enhanced the
      dissociation of bound 125I-galanin. Cholera toxin (CTX) and GTP gamma S abolished
      the activity of the high-affinity binding site, leaving the low-affinity binding
      site. We conclude that galanin may act as an neurotransmitter to inhibit canine
      small intestinal smooth muscle contraction by interaction with a CTX-sensitive G
      protein-coupled specific receptor on muscle membrane. This receptor showed
      different G protein coupling from a synaptosomal receptor previously described in
      the same tissue preparations.

PMID- 7508198
TI  - Inhibition of nitric oxide synthase activity in dispersed gastric muscle cells by
      protein kinase C.
AB  - The present study examined whether NO synthase (NOS) activity in gastric muscle
      cells was inhibited by protein kinase C (PKC). Vasoactive intestinal peptide
      (VIP) increased L-[3H]citrulline production (a coproduct and index of NO
      synthesis) in muscle strips (81.9 +/- 11.6%) and dispersed muscle cells (80.9 +/-
      4.6%) of rabbit stomach. Cholecystokinin octapeptide (CCK-8), carbachol, and
      phorbol 12-myristate 13-acetate (PMA) inhibited VIP-induced L-[3H]citrulline
      production in muscle cells and muscle strips; the inhibition was reversed by
      pretreatment with the PKC inhibitor, calphostin C. The Ca(2+)-mobilizing agents,
      CCK-8, acetylcholine, ionomycin, and KCl, all of which increased PKC activity in
      dispersed muscle cells, did not increase L-[3H]citrulline production. After
      treatment of the cells with calphostin C, all four agents stimulated L
      [3H]citrulline production, although to a lesser extent than VIP (approximately
      50%). VIP-induced relaxation of basal but not carbachol-stimulated tension was
      accompanied by increase in L-[3H]citrulline production and was inhibited by the
      NOS inhibitor NG-nitro-L-arginine (L-NNA). Preincubation of carbachol-treated
      muscle strips with calphostin C restored the ability of VIP to stimulate L
      [3H]citrulline production and the ability of L-NNA to inhibit VIP-induced
      relaxation. We conclude that 1) VIP-stimulated NOS activity is inhibited by
      agents that increase PKC activity in gastric smooth muscle cells, and 2) agents
      that increase both cytosolic free Ca2+ concentration and PKC activity stimulate
      NOS activity only when PKC activity is suppressed.

PMID- 7508199
TI  - A nitric oxide and prostaglandin-dependent component of NANC off-contractions in
      cat colon.
AB  - The actions of NO synthase inhibitors and indomethacin, a cyclooxygenase
      inhibitor, on the nonadrenergic noncholinergic (NANC) mechanical responses of cat
      distal colon were studied in vitro using muscle strips orientated in the axis of
      the longitudinal muscle layer with pelvic nerves attached. Electrical field
      stimulation (EFS) or pelvic nerve stimulation (PNS) caused inhibition of
      spontaneous contractions followed by off-contractions. Indomethacin (10-30
      microM) caused concentration-dependent reductions in amplitude and duration of
      EFS- and PNS-evoked off-contractions but not latency. The NO synthase inhibitors,
      N omega-nitro-L-arginine (L-NNA), N omega-nitro-L-arginine methyl ester (L-NAME)
      and NG-monomethyl-L-arginine (L-NMMA) (each at 100 microM) significantly reduced
      latency, amplitude, and duration of off-contractions evoked by EFS and PNS. This
      inhibition was partially reversed by L-arginine (120 microM) but not by D
      arginine. Incubation of colonic strips with alpha-chymotrypsin (2 U/ml) decreased
      latency, amplitude, and duration of NANC off-contractions. L-NNA reduced
      amplitude, duration, and latency of off-contractions in preparations pretreated
      with alpha-chymotrypsin. Hydroquinone (10-30 microM), a generator of superoxide
      anions, caused significant depression of amplitude, duration, and latency of off
      contractions which was completely reversed by superoxide dismutase (200 U/ml).
      These data suggest that the components of NANC off-contractions evoked by EFS and
      PNS involve peptides, NO, and prostaglandins.

PMID- 7508201
TI  - Endothelial gaps and permeability of venules in rat tracheas exposed to
      inflammatory stimuli.
AB  - This study determined the number of endothelial gaps in venules of the rat
      trachea and related these values to the amount of plasma extravasation after an
      inflammatory stimulus (neurogenic inflammation). From 1 to 30 min after the
      stimulus, vessels were fixed by vascular perfusion, and endothelial cell borders
      were stained with silver nitrate, which made it possible to quantify the number
      and distribution of endothelial gaps. It also was possible to quantify the
      leukocyte attachment sites, to measure the size, shape, and number of endothelial
      cells, and to delineate the architecture of the tracheal vasculature. Sites of
      increased vascular permeability were localized with Monastral blue B, india ink,
      or fluorescent microspheres. After the stimulus, the silver lines around
      endothelial cells of postcapillary venules and collecting venules were
      interrupted by stereotyped silver dots (diam, 1.4 +/- 0.03 microns; +/- SE),
      which were found by electron microscopy to be silver deposits at endothelial
      gaps. The dots were most abundant in the smallest postcapillary venules (diam, 7
      20 microns) where Monastral blue extravasation was greatest. The number of silver
      dots (14.4 +/- 0.7 dots/endothelial cell) and the amount of extravasation were
      maximal 1 min after the stimulus. However, the dots disappeared more slowly (half
      life, 3.2 min) than did the extravasation (half-life, 1.3 min). In addition to
      the silver dots, 64% of the sites at which leukocytes were attached to the
      endothelium were stained with silver. These sites were marked by silver rings
      (diam, 3.4 +/- 0.2 microns) and were most numerous in the largest postcapillary
      venules (diam, 20-40 microns). Most (95%) of the silver rings were located at
      intercellular junctions but usually were not sites of Monastral blue
      extravasation. The results indicate that endothelial gaps at intercellular
      junctions are focal openings, which occupy < 3% of the luminal surface and are
      distinct from sites of leukocyte attachment. The reduction in Monastral blue
      extravasation that precedes the closure of the gaps could result from a decrease
      in the driving force for the convective movement of the tracer or from a decrease
      in the conductance of the gaps, perhaps due to the accumulation of sievelike
      substances within the gaps.

PMID- 7508200
TI  - Neonatal capsaicin treatment decreases airway and pulmonary tissue responsiveness
      to methacholine.
AB  - We studied the effects of selective depletion of neurokinins in sensory nerve
      fibers by capsaicin treatment on the airway and pulmonary tissue responses to
      methacholine. Dose-response curves to aerosolized methacholine were performed on
      anesthetized and mechanically ventilated Wistar rats. Capsaicin (50 mg/kg sc) was
      administered to 2-day-old rats, and the animals were studied after 12 wk. The
      response to each dose of methacholine was determined by measuring changes in
      airway resistance (R(aw)), dynamic pulmonary elastance (Edyn), and pulmonary
      tissue resistance (Rtis). We calculated sensitivity (Kx) as the concentration of
      methacholine required for a one-half maximal response and reactivity as the
      relationship between the maximum response and Kx. Capsaicin treatment resulted in
      significantly greater values of Kx and lower values of reactivity for R(aw),
      Edyn, and Rtis compared with control rats. Morphometric analysis of airways
      showed similar values of the area occupied by smooth muscle but a significantly
      lower (P < 0.02) area of airway epithelium in capsaicin-treated rats. Our results
      suggest that methacholine requires capsaicin-sensitive nerves for part of its
      airway and lung tissue effects.

PMID- 7508202
TI  - Effects of corticoid agonists and antagonists on apical Na+ permeability of toad
      urinary bladder.
AB  - Effects of RU-28362 (glucocorticoid agonist), RU-38486 (glucocorticoid
      antagonist), and RU-26752 (mineralocorticoid antagonist) on the apical Na+
      permeability of toad bladder were measured and correlated with occupancies of
      cytosolic type I (mineralocorticoid) and type II (glucocorticoid) receptors.
      Effects of the above steroids were measured in whole bladders, plasma membrane
      vesicles, and RNA-injected Xenopus oocytes. RU-38486 was found to fully displace
      aldosterone from type II receptors without affecting type I occupancy. Under
      these conditions, RU-38486 inhibited approximately 35% of the effect of
      aldosterone measured in the whole tissue and isolated membranes. Unexpectedly,
      oocytes injected with RNA from tissue stimulated with aldosterone plus RU-38486
      expressed channel activity that was much higher than the sum of activities
      induced by either steroid alone. RU-28362 and RU-26752 at concentrations
      sufficient to fully occupy both receptors had only partial agonistic and
      antagonistic effects, respectively. The results suggest that at least one-third
      of the natriferic action of aldosterone measured in the amphibian urinary bladder
      is mediated by the glucocorticoid receptor. However, some of the effects observed
      cannot be accounted for by a simple receptor occupancy-response scheme.

PMID- 7508203
TI  - IGF binding protein 5 and IGF-I receptor regulation in hypophysectomized rat
      kidneys.
AB  - This study examines growth-regulating adaptations made by the proximal nephron in
      response to hypophysectomy (HYPX). Fourteen days after HYPX, circulating insulin
      like growth factor I (IGF-I) levels were diminished, averaging 97 +/- 7 compared
      with 650 +/- 69 ng/ml in controls (n = 5, P < 0.001). Similar data were observed
      at day 7. Binding of 125I-IGF-I to isolated glomerular membranes and proximal
      tubule basolateral membranes (BLM) was increased in HYPX rats. Affinity labeling
      of membranes with 125I-IGF-I followed by electrophoresis on 6% polyacrylamide
      gels demonstrated two bands, one of approximately 140 kDa and another of > 200
      kDa. The lower-molecular-mass protein, which has been identified as the alpha
      subunit of the IGF-I receptor, and the higher-molecular-mass species were both
      upregulated by HYPX. Ligand blotting with IGF-I demonstrated a 31-kDa protein in
      both membranes, identified by immunostaining as IGF binding protein 5 (IGFBP-5),
      not IGFBP-1 or IGFBP-2. Affinity labeling documented an upregulation of this
      protein in both membranes after HYPX. Ligand blotting demonstrated a 31-kDa
      protein in HYPX cortical but not normal cortical or medullary cytosol that was
      immunostained with IGFBP-5 antibodies. RNA prepared from normal kidney cortical
      tissue demonstrated a 6.0-kb IGFBP-5 transcript, which was increased at day 14
      after HYPX. Adaptations in the kidney after HYPX include an upregulation of the
      IGF-I receptor as well as IGFBP-5.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508204
TI  - Spatially restricted expression of set mRNA in developing rat kidney.
AB  - A somatic translocation event fusing the novel gene set to the putative oncogene
      can has been implicated in the development of acute nonlymphocytic leukemia in
      humans. In this study, full-length cDNAs highly homologous with human set were
      cloned from a rat neonatal kidney library. The expression pattern of set mRNA was
      then examined in developing rat kidney. Two groups of set cDNAs (alpha and beta)
      with different translation initiation sites and open reading frames of 867 and
      831 bp, respectively, were found. The predicted protein products are 33,385 and
      32,085 Da in size and contain approximately 30% acidic residues, over half of
      them clustered at the COOH terminal, thus forming a long acidic tail. No signal
      peptide or membrane-spanning domains were identified, suggesting an intracellular
      protein product. By ribonuclease protection assay, both alpha and beta variants
      of set were expressed in kidney. On Northern blots of total kidney RNA, 3.0- and
      2.2-kb mRNAs hybridized with the labeled set cDNA probe. Expression of both
      transcripts was four- to eightfold greater in neonatal compared with adult rat
      kidney. When neonatal rat kidneys were examined for set mRNA expression by in
      situ hybridization with 35S-labeled riboprobe, expression was densely localized
      in the cortical region of morphogenesis over primitive nephron structures,
      including S-shaped bodies. Thus mRNA for Set, a putative intracellular protein
      involved in leukemogenesis, is expressed in kidney.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508205
TI  - Pharmacological evidence that calcitonin gene-related peptide is implicated in
      cerebral autoregulation.
AB  - In anesthetized rats, we examined the possibility that calcitonin gene-related
      peptide (CGRP, a neuropeptide) released in response to transient hypotension may
      contribute to the reflex autoregulation of cerebral blood flow. Changes in pial
      arterial diameter (mean 33.0 +/- 1.1 microns) with changes in systemic arterial
      blood pressure (mean 101.9 +/- 2.7 mmHg) were observed directly through a closed
      cranial window. In capsaicin-treated rats (depletor of CGRP and substance P, 50
      nmol capsaicin injected intracisternally 24 h before experiment), vasodilatation,
      which was evoked on transient hypotension, and vasoconstriction on reverse of
      hypotension were markedly attenuated or almost abolished. When changes in pial
      arterial diameter were plotted as a function of changes in blood pressure, the
      slopes of regression lines for vasodilatation and vasoconstriction were markedly
      reduced after capsaicin treatment. Similar reductions were evidenced under
      suffusion of CGRP antibody serum (1:1,000) and after CGRP receptor
      desensitization but not after substance P receptor desensitization. Pretreatment
      with glibenclamide, a K(+)-channel antagonist, also caused severe alterations in
      the autoregulatory vasomotor responses to hypotension and its reverse. Suffusion
      with mock cerebrospinal fluid, containing either CGRP or cromakalim, a K(+)
      channel opener, dilated the pial artery in a concentration-dependent manner, and
      their effects were antagonized by glibenclamide. Substance P produced a
      vasodilatation, which was unaffected by glibenclamide.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508206
TI  - Mechanism of substance P-induced hyperpolarization of porcine coronary artery
      endothelial cells.
AB  - Substance P (SP) is a potent endothelium-dependent vasodilator, and in porcine
      coronary arterioles the vasodilatory action of SP appears to be mediated entirely
      by nitric oxide. We tested the hypothesis that SP induces hyperpolarization in
      porcine coronary artery endothelial cells (PCAECs) by activating Ca(2+)-activated
      K+ (KCa) channels. With a bath Ca2+ concentration ([Ca2+]) of 1 mM, 10 nM SP
      elicited an increase in cytosolic [Ca2+] ([Ca2+]i) from a baseline of 25 +/- 4 nM
      to a peak of 808 +/- 120 nM, followed by a slowly declining plateau phase, which
      was absent in Ca(2+)-free bath and was abolished by addition of extracellular
      lanthanum or nickel. Whole cell current-clamp recordings revealed that the time
      course of SP-induced [Ca2+]i increases correlated closely with membrane
      hyperpolarization from an average resting potential of -42 +/- 2 to a peak of -79
      +/- 2 mV. Under voltage clamp, SP stimulated whole cell currents with reversal
      potentials strongly dependent on extracellular K+ concentration. In 62% of
      patches tested, single-channel recordings revealed an intermediate-conductance K+
      channel with activation highly correlated with the SP-induced [Ca2+]i increase.
      These results suggest that, in PCAECs, SP induces Ca2+ release from stores along
      with Ca2+ influx which activate a KCa channel leading to hyperpolarization. This
      may increase the driving force for Ca2+ entry and thus modulate endothelium
      derived nitric oxide release.

PMID- 7508207
TI  - Characterization of E-selectin expression in vivo with use of a radiolabeled
      monoclonal antibody.
AB  - We have studied endothelial luminal surface expression of E-selectin in vivo in
      the pig. Intravenous interleukin-1 (IL-1, 5-micrograms/kg bolus +/- 50-ng.kg-1 x
      min-1 infusion for 2 h) induced E-selectin expression in many organs, as shown by
      immunostaining and selective clearance of intravenous 111In- or 99mTc-labeled
      anti-E-selectin monoclonal antibody (MAb 1.2B6) compared with radiolabeled
      immunoglobulin G1 control. Specific clearance of MAb 1.2B6 commenced 30-45 min
      after intravenous IL-1. Skin sites injected with IL-1, tumor necrosis factor,
      phytohemagglutinin, or phorbol myristate acetate at various times (45 min-24 h)
      before exsanguination showed specific accumulation of MAb 1.2B6 when 99mTc-MAb
      1.2B6 and 111In-control immunoglobulin G1 were injected intravenously 10 min
      before exsanguination. This was maximal in 2-h IL-1 and tumor necrosis factor
      lesions and after 9 h in phytohemagglutinin and phorbol myristate acetate
      lesions. This novel approach has allowed us to quantify changes in vascular
      luminal expression of E-selectin in models of inflammation involving systemic and
      localized endothelial cell activation and has considerable potential for
      analyzing these changes in relation to leukocyte traffic and other manifestations
      of inflammatory responses in vivo.

PMID- 7508208
TI  - Effect of competitive antagonism of NO synthetase on weight and food intake in
      obese and diabetic mice.
AB  - Recent studies have suggested a role for nitric oxide (NO) in the regulation of
      food intake. The present studies were undertaken to examine the effects of the
      administration of a nitric oxide synthetase inhibitor, NG-nitro-L-arginine methyl
      ester (L-NAME), on food intake and weight loss. Two genetically obese mice, the
      ob/ob and db/db strains, and their lean heterozygote littermate controls, ob/c
      and db/c, served as subjects. In the first experiment, we demonstrated that L
      NAME (100 micrograms/kg) given twice over a feeding period of 7 h/day produced a
      small but significant weight loss in ob/ob mice but not in their lean-genotype
      controls (P < 0.05). In the second experiment, a higher dose of L-NAME (100
      mg/kg), given twice daily, produced a marked effect on body weight, with the
      ob/ob mice losing approximately 10% of their body weight in 9 days. The ob/c mice
      showed a lesser decrease in body weight. Food intake was decreased on all 9 days
      in the ob/ob mice (P < 0.01). A small decrease in body weight and food intake was
      seen in db/db and db/c mice receiving L-NAME. These studies provide further
      evidence for a role of nitric oxide in the modulation of food intake and weight
      gain.

PMID- 7508209
TI  - Metabolic and neurochemical profiles in insulin-treated diabetic rats.
AB  - Plasma glucose concentration was measured at 3-h intervals in streptozotocin
      induced diabetic rats placed on various insulin replacement regimens using three
      different kinds of insulin. High insulin dosages produced at least periodic
      hypoglycemia, even though there were no overt signs of insulin overdose. Low- and
      single-dose regimens produced periods of hyperglycemia. Both high and low doses
      of protamine zinc insulin normalized diabetes-induced reductions in 5
      hydroxyindole-3-acetic acid [5-HIAA; the principal metabolite of 5
      hydroxytryptamine (5-HT)] and 5-HT turnover (5-HIAA/5-HT), despite the failure of
      the low-dose regimen to normalize plasma glucose. Diabetic rats evidenced
      continued hyperphagia and hyperdipsia during insulin treatment, and insulin
      treatment also induced hyperphagia and excessive weight gain in nondiabetic rats.
      Insulin treatment only partially normalized diabetes-induced adrenal hypertrophy.
      Adrenal hypertrophy is an indication of a continued stresslike physiological
      state in diabetes even during insulin therapy. This state may be involved in the
      enhanced risk in diabetic humans for development of anxiety disorders and
      clinical depression.

PMID- 7508210
TI  - Immunohistochemical demonstration of the synthesis enzyme for nitric oxide and of
      comediators in neurons and chromaffin cells of the human adrenal medulla.
AB  - Within the human adrenal medulla immunoreactivity for the nitric oxide (NO)
      generating enzyme nitric oxide synthase (NOS) was demonstrated in neurons, nerve
      fibres and chromaffin cells. Correlation of NOS-immunoreactivity with
      immunostaining for the peptides neuropeptide Y, somatostatin, substance P or
      vasoactive intestinal polypetide and for the catecholamine synthesis-enzyme
      tyrosine hydroxylase, respectively, in nerve cell bodies revealed colocalization
      of NOS only with substance P. Sparse intramedullary NOS-immunoreactive varicose
      nerve fibres associated with blood vessels or with chromaffin tissue were devoid
      of immunoreactivities for tyrosine hydroxylase or for the investigated peptides.
      Small NOS-immunolabeled cells belonged to the catecholamine-containing chromaffin
      cell population and costored VIP, but were distinct from the somatostatin- or
      neuropeptide Y- immunostained chromaffin subpopulations. The localization of NOS
      in distinct structural components of the human adrenal medulla indicates that NO
      is produced in different cell types and may reflect a differential role of this
      messenger system in autonomic control of adrenal gland function.

PMID- 7508211
TI  - [Does the use of nasal vasoconstrictor agents change tomodensitometric images of
      nasosinusal polyposis?].
AB  - This study compared the results of the CT scan of the paranasal sinuses in nasal
      polyposis patients before and after a topical vasoconstrictor application on the
      nasal mucosa. No change have been observed either on the maxillary and ethmoidal
      sinuses, or the middle meatus. On the other hand, an important retraction was
      observed on the nasal mucosa, in particular on the inferior turbinate. Then, the
      application of a topical vasoconstrictor on the nasal mucosa does not seem
      necessary in order to explore the sinuses in patients with nasal polyposis.

PMID- 7508212
TI  - The association between hepatitis C virus infection and in vitro activation of
      the complement system.
AB  - The phenomenon of in vitro activation of the classical complement pathway at low
      temperatures (4-21 degrees C) is known as cold activation, and has been suggested
      to be associated with non-A, non-B hepatitis. We re-examined the association by
      using newly developed markers of hepatitis C virus (HCV) infection. Twenty-one
      cases randomly selected from those fulfilling the screening criteria of
      complement cold activation all showed evidence of HCV infection. More than half
      of 55 HCV antibody-positive cases selected randomly from our laboratory samples
      showed a tendency towards cold activation, whereas none of the HCV antibody
      negative sera showed cold activation. All the HCV antibody-positive cases were
      negative in cold activation when CH50 was assayed with plasma. These results,
      taken together, indicate that cold activation of the complement system is
      strongly associated with HCV infection.

PMID- 7508213
TI  - Assessment of atypicality: an adjunct to prenatal screening for Down's syndrome
      that facilitates detection of other abnormalities.
AB  - Current software used for assessment of the risk of Down's syndrome may give
      misleading risk estimates if applied to other abnormalities. Often the
      abnormality is reflected in maternal serum alpha-fetoprotein and human chorionic
      gonadotrophin levels and is then translated into a low risk for Down's syndrome
      that may not be recognized as significantly atypical of normality. We regard this
      as a serious deficiency in the current Down's syndrome risk reporting algorithm,
      and suggest a modification that allows the problem to be overcome.

PMID- 7508214
TI  - [Urethral resistance and bladder contractility].
AB  - Urinary difficulty results from an imbalance between deux forces: expulsive and
      retentive forces. Prostatic hypertrophy for instance only represents one of these
      forces. This presentation describes the numerous factors responsible for detrusor
      contractility which has been often ignored in the assessment of prostatic
      hypertrophy. The notion of urethral resistance is explained as a ratio of
      pressure flow which represents the only way to assess the obstructive factor.

PMID- 7508215
TI  - Effects of 1 alpha,25-dihydroxy-vitamin D3 and calcipotriol on organotypic
      cultures of outer root sheath cells: a potential model to evaluate antipsoriatic
      drugs.
AB  - In the human hair follicle, outer root sheath (ORS) cells constitutively express
      the hyperproliferation-associated keratins 6, 16 and 17 instead of keratins 1 and
      10 found in interfollicular epidermis. In organotypic cultures. ORS cells form a
      stratified epithelium which in many respects resembles psoriatic skin: it has a
      hyperplastic tissue architecture and a poorly developed granular layer, and
      expresses hyperproliferation-associated keratins. Therefore, we studied the
      effects of the antipsoriatic compounds 1 alpha,25-dihydroxy-vitamin D3 (1
      alpha,25-(OH)2-D3) and its synthetic derivative calcipotriol on cultured ORS
      cells. In monolayer cultures, 10(-6) M 1 alpha,25-(OH)2-D3 or calcipotriol
      completely blocked ORS cell proliferation. This inhibitory effect was
      substantially reduced at 10(-8) M. Incubation of organotypic ORS cultures with
      both vitamin D analogues resulted in a marked thinning of the living cell
      compartment concomitant with a thickening of the horny layer. A reduced
      expression of differentiation markers such as keratins 10, 16 and 17, involucrin
      and filaggrin paralleled the thinning of the stratum Malpighi. As determined by
      quantification of BrdU-positive cells, ORS cell proliferation was apparently not
      affected by the vitamin D analogues, indicating that these compounds mainly
      operate by accelerating the differentiation pathway within the suprabasal living
      cell compartment. No alteration in the expression of the alpha 6- and beta 1
      integrin chains was found.

PMID- 7508217
TI  - [Prostatic melanosis].
AB  - We report a case of prostatic melanosis in a 68-year-old patient. Although
      uncommon, some authors have reported an incidence of 4-10% for benign pigmented
      lesions of the prostate. It is important to distinguish this from the blue nevus
      where melanin deposits only involve the prostatic stroma. We discuss the theories
      explaining the origin of melanin in the prostate and its presence in the
      epithelium. The gross and microscopic findings of these conditions are described.

PMID- 7508218
TI  - [Leiomyosarcoma of the prostate].
AB  - Leiomyosarcoma of the prostate is a very uncommon malignant tumor arising from
      the smooth muscle cells of the prostate gland. We report on a 72-year-old patient
      who underwent surgery for benign prostatic hyperplasia. The pathological analysis
      following retropubic resection, however, revealed a leiomyosarcoma and an
      extended cystectomy and pelvic tumorectomy were performed after preoperative
      radiotherapy. The patient is alive with local recurrence at four years follow up.

PMID- 7508216
TI  - Histamine-releasing factor(s) in sera of uraemic pruritus patients in a possible
      mechanism of UVB therapy.
AB  - Uraemic pruritus is poorly understood despite the high incidence among chronic
      renal failure (CRF) patients undergoing haemodialysis. Serum histamine levels
      have been shown to be elevated in CRF patients with itching, and ultraviolet B
      (UVB) therapy, even if applied to only part of the body surface, has been
      reported to be beneficial for the generalized relief of the pruritus. A local
      mechanism of UVB action is suggested by evidence that UVB radiation is able to
      suppress histamine release from mast cells. However, detailed systemic
      mechanism(s) remain obscure. Sera from patients with or without uraemic pruritus
      were incubated with purified rat peritoneal mast cells and the resulting
      histamine release was compared. A higher histamine release was obtained with sera
      from uraemic pruritus patients (44.60 +/- 6.32%, n = 9, P < 0.005) than with sera
      from patients without itching (19.71 +/- 3.14%, n = 5, P > 0.25) and with normal
      control sera (23.62 +/- 7.14%, n = 6). This increased histamine release was dose
      dependently restored to spontaneous release levels in five of seven patients by
      pre-exposure of the sera to UVB in vitro. From these results, sera of CRF
      patients with uraemic pruritus were considered to contain some histamine
      releasing factor(s) which was depleted or diminished by UVB irradiation,
      suggesting a possible systemic mechanism of UVB action.

PMID- 7508219
TI  - Detrimental hemodynamic effects of nitric oxide synthase inhibition in septic
      shock.
AB  - OBJECTIVE: To investigate the physiologic effects of nitric oxide synthase
      inhibition with N-nitro-L-arginine methyl ester in an acute resuscitated model of
      porcine septic shock. DESIGN: Randomized control trial. SETTING: Animal research
      facility. STUDY SUBJECTS: Domestic Yorkshire swine. INTERVENTIONS: Twenty-four
      animals were randomly divided into one of four treatment groups as follows:
      normal saline resuscitation (NSR) (control group); NSR plus 200 micrograms/kg of
      lipopolysaccharide (LPS) at 1 hour after baseline (LPS group); NSR, LPS, and a
      continuous infusion of 50 micrograms/kg per minute of N-nitro-L-arginine methyl
      ester (NAME) at 1 hour after baseline (LPS/NAME group); and NSR and NAME (NAME
      group). All animals received NSR at 1 mL/kg per minute starting at baseline. MAIN
      OUTCOME MEASURES: Mean arterial pressure (MAP), systemic vascular resistance
      index (SVRI), mean pulmonary arterial pressure (MPAP), and pulmonary vascular
      resistance index (PVRI) were measured at baseline and hourly for 4 hours. Values
      at baseline and 3 hours are given below as mean (+/- SE). RESULTS: All variables
      remained unchanged in the control group. The administration of LPS produced a
      systemic hyperdynamic response characterized by a decrease in MAP and SVRI from
      66.0 +/- 3.9 to 55.0 +/- 2.8 mm Hg (P < .05) and from 422.0 +/- 22.0 to 272.0 +/-
      29.0 mm Hg.min.kg/L (P < .05), respectively. The administration of LPS produced
      an increase in MPAP and PVRI from 16.3 +/- 0.8 to 30.0 +/- 1.3 mm Hg (P < .05)
      and from 37.0 +/- 5.3 to 119.0 +/- 13.0 mm Hg.min.kg/L (P < .05), respectively.
      In the LPS/NAME group, NAME infusion normalized MAP and increased SVRI from 506.0
      +/- 40.0 to 642.0 +/- 72.0 mm Hg.min.kg/L (P < .05). Infusion of NAME potentiated
      LPS-induced pulmonary hypertension, increasing MPAP and PVRI from 16.8 +/- 0.6 to
      36.0 +/- 2.8 mm Hg (P < .05) and from 59.0 +/- 3.5 to 319.0 +/- 64.0 mm
      Hg.min.kg/L (P < .05), respectively. Infusion of NAME alone increased MAP from
      74.0 +/- 1.3 to 100.0 +/- 4.1 mm Hg (P < .05) and had no significant effect on
      MPAP and PVRI. CONCLUSIONS: The potentiation of LPS-induced pulmonary
      hypertension following NAME infusion suggests that inhibition of nitric oxide
      synthase may have a limited role in the treatment of septic shock.

PMID- 7508221
TI  - Changes in polymorphonuclear leukocyte surface and plasma
      bactericidal/permeability-increasing protein and plasma lipopolysaccharide
      binding protein during endotoxemia or sepsis.
AB  - OBJECTIVE: To evaluate changes in levels of polymorphonuclear leukocyte surface
      bactericidal/permeability-increasing protein (BPI), plasma BPI, and plasma
      lipopolysaccharide (LPS) binding protein (LBP) in normal human volunteers
      administered Escherichia coli LPS and in patients with sepsis and gram-negative
      infections. DESIGN: Survey; case series. SETTING: Clinical research center and
      surgical intensive care unit of a medical school and an associated tertiary care
      hospital. PATIENTS OR OTHER PARTICIPANTS: Volunteers (n = 10) screened prior to
      study by history and physical examination to exclude those with underlying
      diseases or hematologic abnormalities. Consecutive sample of surgical intensive
      care unit patients (n = 10) meeting criteria for sepsis syndrome with gram
      negative infection. An additional patient with systemic inflammatory response
      syndrome but no gram-negative infection. All patients were studied on meeting the
      criteria. Three of the patients with sepsis syndrome and the patient with
      systemic inflammatory response syndrome were evaluated on recovery (approximately
      25 days after initial study). Because these studies in volunteers and patients
      overlapped temporally, the control values were those of volunteers evaluated
      prior to LPS administration. No matching was employed. MEASUREMENTS AND RESULTS:
      Compared with controls, LPS-challenged volunteers and patients with sepsis both
      exhibited significant granulocytosis (P < .01) and increased concentrations of
      polymorphonuclear leukocyte surface BPI (P < .01) and of plasma LBP (P < .01).
      Plasma BPI concentrations were increased (P < .01) in volunteers following LPS
      administration. There was a trend toward increased concentrations of plasma BPI
      in patients, but this was not significant relative to controls. Maximum
      concentrations of plasma LBP were approximately 250- and 3000-fold higher than
      plasma BPI concentrations in endotoxemic volunteers and in patients,
      respectively. CONCLUSIONS: Circulating polymorphonuclear leukocytes increase
      expression of BPI in response to LPS or gram-negative sepsis. Subsequently,
      concentrations of plasma BPI and LBP increase. Because both LBP and BPI bind to
      LPS, it is suggested that endogenously derived plasma levels of BPI are likely to
      be inadequate to compete for LPS binding to the much more abundant LBP in the
      circulation.

PMID- 7508222
TI  - Diagnosis and management of extrauterine pregnancies.
AB  - This study was based on 16 women provisionally diagnosed as having extrauterine
      pregnancies. Of these, 13 (81.3%) were confirmed as positive at operation.
      Patients were managed according to 1 of 3 regimens; 1) methotrexate (n = 4), 2)
      methotrexate followed by surgery (n = 3) and 3) surgery (n = 6). Serial blood
      samples, collected before and after treatment, were analyzed for ovarian
      (oestradiol, E2; progesterone, P4) uterine (placental protein 14, PP14) and
      placental markers (chorionic gonadotrophin, HCG; pregnancy-associated plasma
      protein-A (PAPP-A). Of the pretreatment samples, only 30.4% and 41.7% were
      depressed for PP14 and HCG, respectively. By contrast, the diagnostic value of
      PAPP-A (77.8%) and P4 (87.5%) was greater. Biochemical monitoring of treatment
      was best achieved with trophoblastic derived antigens (HCG), whereas antigens of
      maternal origin demonstrated widely varied responses. This study established the
      effectiveness of chemotherapy for treatment of tubal pregnancies as an
      alternative to surgery, but if a biochemical marker is required, the marker of
      choice is HCG.

PMID- 7508220
TI  - Differential induction of nitric oxide synthase in hepatocytes during endotoxemia
      and the acute-phase response.
AB  - OBJECTIVE: Nitric oxide (NO) is a potent biologic mediator produced by
      hepatocytes following exposure to cytokines and lipopolysaccharide (LPS). These
      cytokines are also known to regulate induction of the hepatic acute-phase
      response. The objective of this study was to determine whether inducible nitric
      oxide synthase (iNOS), the enzyme that produces NO, is expressed as part of the
      hepatic acute-phase response. DESIGN: The gene expression for inducible NOS
      (iNOS) as well as alpha 1-acid glycoprotein (AGP), an established acute-phase
      reactant, was measured by Northern blot analysis in rat hepatocytes in vivo
      during endotoxemia (LPS injection) and during the acute-phase response produced
      by hindlimb turpentine injection. Hepatocyte iNOS messenger RNA (mRNA) levels
      were correlated with iNOS activity and circulating plasma nitrite and nitrate
      levels. In vitro, iNOS and AGP mRNA levels were determined in cultured
      hepatocytes stimulated with interleukin 6 (IL-6), interleukin 1 beta (IL-1 beta),
      tumor necrosis factor alpha (TNF-alpha), or dexamethasone. RESULTS: The AGP mRNA
      levels were increased in vivo following both LPS and turpentine injection, while
      iNOS expression was induced only by LPS injection. Hepatocyte iNOS activity and
      plasma nitrite and nitrate levels also increased after LPS treatment. In vitro,
      the cytokine combination IL-6, IL-1 beta, and TNF-alpha induced hepatocyte iNOS
      expression but had minimal effects on AGP in the absence of dexamethasone.
      Addition of dexamethasone alone markedly increased AGP mRNA levels, with further
      increases seen with TNF-alpha or IL-1 beta addition. In contrast, dexamethasone
      decreased iNOS expression. CONCLUSION: The results show that hepatocyte iNOS
      expression is not part of the acute-phase response induced by remote inflammation
      and indicates that iNOS is differentially regulated from the acute-phase
      reactant, AGP.

PMID- 7508223
TI  - Primary liver carcinoma complicating pregnancy.
AB  - Primary hepatic carcinoma complicating pregnancy has been sporadically reported
      in the literature. Its association with grossly raised serum alphafetoprotein
      values is of particular interest to obstetricians who perform routine maternal
      alphafetoprotein screening in the second trimester. A case with favourable
      maternal and fetal outcome is presented.

PMID- 7508224
TI  - Primary endometrial squamous cell carcinoma with long-term survival.
AB  - Primary endometrial squamous cell carcinoma is a rare variant of uterine
      epithelial malignancy. A review of records over a 10-year period at a major
      referral centre for gynaecological malignancy identified 4 patients with this
      disease. They were treated primarily by surgery, with adjuvant radiotherapy or
      chemotherapy in 3 cases. In comparison to previously reported cases the length of
      survival for these patients was long.

PMID- 7508225
TI  - N-acetylcysteine inhibits diesel extract mutagenicity in the Ames test and SCE
      induction in human lymphocytes.
AB  - N-Acetylcysteine (NAC) has been reported to decrease genotoxicity induced by
      several mutagens. In this paper, the desmutagenic effect of NAC on a complex
      mixture, such as diesel extract, has been analyzed. Studies have been carried out
      in vitro with the Ames test (reverse mutations on TA98, TA100, and TA104 strains)
      and sister chromatid exchanges assay (SCE) in human lymphocytes. NAC inhibits
      diesel genotoxicity in both assays. NAC also inhibits the mutagenicity of 1,8
      dinitropyrene (1,8-DNP) and 1-nitropyrene (1-NP) known to be present in diesel
      exhaust and to be activated by cellular O-transacetylases and nitropyrene
      reductases. NAC inhibits also the induction of SCE in human lymphocytes by diesel
      extract. These results, and those obtained by the preincubation of NAC with
      cells, suggest that the inhibition also takes place inside the cell.

PMID- 7508226
TI  - Inhibition of malignant tumor cell invasion: an approach to anti-progression.

PMID- 7508227
TI  - HIV resistance to reverse transcriptase inhibitors.

PMID- 7508229
TI  - Ruthenium red inhibits selectively chromaffin cell calcium channels.
AB  - The effect of Ruthenium red (RR) on ionic currents and catecholamine secretion
      was studied in chromaffin cells. This polycation inhibited 59 mM potassium
      stimulated 45Ca2+ uptake in a concentration-dependent manner (IC50 = 5 +/- 0.2
      microM). This effect was more evident at extracellular calcium concentrations
      over 1 mM and was not abolished by neuraminidase pretreatment. RR also inhibited
      potassium-stimulated catecholamine secretion (IC50 = 6 +/- 0.9 microM). These
      results were corroborated by patch-clamp in whole-cell recordings. RR inhibited
      chromaffin cell calcium currents (IC50 = 7 microM) without affecting
      significantly either sodium or potassium currents. Radioligand binding studies in
      adrenomedullary plasma membranes showed that RR inhibited [125I]omega-conotoxin
      GVIA binding but it had no effect on specific binding of [3H]nitrendipine. The
      effect of the RR on calcium currents was additive with the inhibitory effect
      observed with 10 microM nitrendipine. The residual dihydropyridine-resistant
      calcium current was inhibited with a potency similar to that determined under
      control conditions in the absence of nitrendipine. These results demonstrate that
      RR selectively inhibits calcium channels; however, this polycation was not
      selective for a particular calcium channel subtype.

PMID- 7508228
TI  - The in vitro influence of sulfated bis-lactobionic acid amides on O6-alkylguanine
      DNA alkyltransferase, DNase I, nucleic acid synthesis and chromatin structure.
AB  - The influence of four sulfated bis-lactobionic acid amides (BLAA) of molecular
      weights between 2388 and 2514 on O6-alkylguanine-DNA alkyltransferase (AT), DNase
      I and nucleic acid synthesis as well as on nucleoid sedimentation and the
      viscosity of alkaline lysates of chicken embryo cells was studied in vitro. The
      activities of AT and DNase I were inhibited by BLAA in a dose-dependent manner.
      Depending on the polyanion used, concentrations depleting AT activity by 50%
      ranged between 3.5 and 7.0 microM, whereas BLAA concentrations of almost 250-320
      microM were needed to halve DNase I activity. At concentrations above 8 microM,
      BLAA decreased scheduled DNA synthesis in a dose-dependent fashion whereas RNA
      synthesis remained unchanged even at the highest BLAA concentrations used (2 mM).
      In chicken embryo brain cells BLAA exerted a biphasic effect on the nucleoid
      sedimentation and the viscosity of alkaline cell lysates reflecting a decrease in
      chromatin compactness at lower BLAA concentrations (10-100 microM) and an
      increase in chromatin compactness at higher polyanion concentrations (> or = 200
      microM). The remarkably high sensitivity of the nuclear enzyme AT deserves
      further investigation in regard to the fate of the polyanions within cells and
      tissues.

PMID- 7508230
TI  - New sulfonated distamycin A derivatives with bFGF complexing activity.
AB  - Tumor-induced neoangiogenesis is an essential event for solid tumor growth.
      Therefore, a compound able to block angiogenesis-promoting factors could have
      antitumor activity. The polysulfonated naphthylurea suramin is hypothesized to
      have this mode of action. A series of sulfonated distamycin A derivatives have
      been synthesized with the objective of identifying novel compounds able to
      complex basic fibroblastic growth factor (bFGF) and other factors involved in
      tumour angiogenesis, and consequently to block the angiogenic process. These new
      compounds have been characterized for their ability to inhibit bFGF binding, in
      vivo bFGF-induced angiogenesis and neovascularization of the chorioallantoic
      membrane, in comparison with suramin. The two most active compounds, FCE 26644
      [7,7'-(carbonyl-bis(imino-N-methyl-4,2-pyrrolecarbonyl-imino(N-met hyl-4,2-
      pyrrole)carbonylimino))-bis(1,3-naphthalenedisulfonic acid)] and FCE 27164 [7,7'
      (carbonyl-bis(imino-N-methyl-4,2-pyrrolecarbonyl-imino(N-met hyl-4,2- pyrrole)
      carbonylimino)-bis (1,3,5-naphthalenetrisulfonic acid)] have been selected for
      extended evaluation. Both compounds are active in inhibiting platelet-derived
      growth factor beta (PDGF beta) and interleukin-1 beta binding. Two different
      assays have been performed to study their mode of action: the sequential binding
      assay on bFGF and PDGF receptors and the bFGF-induced tyrosine phosphorylation
      assay. The results of the two assays are in agreement and indicate that no
      activity is observed if FCE 26644, FCE 27164 and suramin are administered as
      pretreatment, when a direct interaction of the compounds with bFGF and PDGF
      receptors is required. Conversely, inhibitory activity is observed when the
      compounds are allowed to form complexes with the growth factors themselves.

PMID- 7508231
TI  - Design, synthesis and investigation of mechanisms of action of novel protein
      kinase C inhibitors: perylenequinonoid pigments.
AB  - A series of perylenequinonoid pigments (PQPs) and related compounds were
      synthesized and screened for the inhibition of protein kinase C (PKC), a key
      enzyme involved in cellular differentiation and proliferation, and a potential
      target for anticancer and antiviral chemotherapeutic drugs. This study has
      established PQPs as efficient PKC inhibitors, and elucidated aspects of the light
      enhanced action mode of the PKC inhibitors. Comparative studies between natural
      and synthetic PQPs led to the recognition of the effect of certain structural
      features of PQPs on PKC inhibition, including the skeleton of the 3,10-dihydroxy
      4,9-perylenequinonoid chromophore and the configuration of the two side chains at
      positions 1 and 12. Calphostin C was identified as a superior PKC inhibitor of
      the POP class, and with the latter as a representative structure, we investigated
      the mechanism of PKC inhibition by PQPs via electron paramagnetic resonance
      spectroscopy in conjunction with the spin-trapping technique, absorption and
      fluorescence spectroscopy, photochemical and photobiological studies, and enzyme
      methodology. Multiple modes of action are suggested for PKC inhibition,
      comprising the following steps: (1) the binding of PQPs to the PKC regulatory
      domain via complexation; (2) the photobonding between mercapto groups of PKC
      cysteine residues and the PQP quinonoid moiety; and (3) the PQP-sensitized
      photodamage of PKC via Type I and/or Type II photosensitization.

PMID- 7508232
TI  - Immunohistochemical analysis of p53 protein expression in benign and malignant
      skin tumors using a panel of anti-p53 antibodies.
AB  - The expression of p53 in a variety of benign and malignant skin lesions has been
      first assessed in frozen sections and then compared with the results obtained in
      corresponding paraffin-embedded sections using various immunohistochemical
      staining methods with a panel of anti-p53 antibodies. Of the 48 benign and
      malignant skin lesions studied, 46(96%) had corresponding paraffin sections and
      immunohistochemical results obtained with DO7 on frozen and paraffin sections
      were concordant in 97%, qualitatively. Using streptavidin-biotin complex method,
      p53 was identified in 33% of dysplastic squamous lesions, 50% of squamous cell
      carcinomas (SCCs) and 36% of basal cell carcinomas (BCCs) on frozen section,
      whereas 25% of dysplastic squamous lesions, 40% of SCCs, and 32% of BCCs showed
      p53 positivity on paraffin-embedded sections. In frozen sections, the same
      regions of each specimen exhibited similar topographic patterns of positive
      immunoreactivity with both monoclonal antibodies, PAb 1801 and DO7. In contrast,
      immunohistochemical staining with polyclonal antibody, CM-1, gave poor
      morphologic resolution, although effective in paraffin-embedded sections.

PMID- 7508233
TI  - Rotating stations: an innovative approach to third-year medical student education
      in physical medicine and rehabilitation.
AB  - Education of medical students is an important component of physical medicine and
      rehabilitation training programs. A one-day combined lectures/rotating stations
      conference was designed to introduce physical medicine and rehabilitation to
      third year medical students during the academic years 1991 through 1993. Pre- and
      post-testing allowed objective measurement of student knowledge of physical
      medicine and rehabilitation. The lectures and rotating stations were evaluated,
      and the feedback was used to improve subsequent conferences. Pre- and post-tests
      indicated increased student knowledge, and interest in physical medicine and
      rehabilitation doubled in each class that participated. This instructional method
      increases third year medical student exposure to physical medicine and
      rehabilitation in a cost-effective and efficient manner.

PMID- 7508234
TI  - Prevalence and clinical significance of anomalous muscular band in the left
      atrium.
AB  - The significance of left ventricular false tendon and right atrial anomalous
      muscular band has been previously reported. As well as in the right atrium,
      anomalous muscular band is sometimes observed in the left atrium. To evaluate the
      prevalence and clinical significance of the left atrial anomalous band, a clinico
      pathologic study was performed among 1,100 autopsies over 60 years. The following
      results were obtained: (1) Pathologically, the incidence of the left atrial
      anomalous band was 2% (22 cases among 1,100 autopsies). The anomalous band
      connected the left atrial side of fossa ovalis with the other areas of left
      atrial endocardium in most of the cases (19 cases). The cases with the bands had
      Chiari's network and patent foramen ovale at the same time more frequently than
      those without the bands (Chiari's network: 27% vs 8%, p < 0.01, patent foramen
      ovale: 23% vs 8%, p < 0.05). Microscopically, the anomalous band was composed of
      fibrous and muscular tissues. (2) Clinically, premature atrial complex was more
      frequently observed among the cases with left atrial anomalous bands than those
      without the bands (41% vs 11%, p < 0.01). In conclusion, left atrial anomalous
      band seemed to be one of congenital abnormalities which was associated with
      Chiari's network and patent foramen ovale in origin, and might be one of the
      causes of supraventricular arrhythmias.

PMID- 7508235
TI  - Temperature and androgens regulate the biosynthesis of secretory proteins from
      rabbit cauda epididymidis.
AB  - We have compared the biosynthesis of secretory proteins in rabbit cauda
      epididymidis maintained for 15 days at abdominal temperature with that of the
      scrotal cauda. Explants from both situations were incubated in vitro in the
      presence of [35S] methionine, and the labelled proteins released into the
      incubation medium were analyzed by polyacrylamide gel electrophoresis. Body
      temperature specifically inhibited the synthesis of at least two polypeptides of
      43 kDa and 21 kDa (designated EP21), whereas the synthesis of polypeptides of 80,
      39, 31, and 24 kDa was increased. These changes resembled those produced by
      castration, but androgen treatment was not able to reverse the effect of body
      temperature. To confirm these observations, poly(A)+ RNA from the scrotal and the
      abdominal cauda respectively, was translated in vitro and the synthesized
      products were immunoprecipitated with an antibody against EP21 polypeptide. Both
      castration and body temperature strongly decreased the concentration of EP21
      mRNA. In vivo testosterone administration restored the content of EP21 mRNA in
      cauda from castrated animals, but not in cauda maintained at body temperature.
      The changes observed might be related to the adverse effect of body temperature
      on sperm storage in the cauda epididymidis.

PMID- 7508236
TI  - Immunotargeting with monoclonal cytokeratin 8 antibodies of human urothelial
      cancer transplanted to nude mice.
AB  - The possibility of using cytokeratin antibodies for the radioimmunolocalization
      of urinary bladder cancer was studied. A monoclonal murine IgG antibody was
      raised against cytokeratin 8 and labelled with iodine-125; normal murine IgG was
      used for control purposes. The urothelial cancer cell line RT4 was transplanted
      into immunodeficient nude mice. The anti-cytokeratin 8 antibody was administered
      intraperitoneally and its uptake in the tumour and other organs was analyzed with
      a computerized gamma camera. Optimal scintigraphic visualization occurred 11 days
      after antibody administration. The tumour/blood ratio of the specific antibody
      was 5.64 (+/- 5.01 SD) on day 11, compared with 0.73 (+/- 0.35 SD) in the
      control. Autoradiography demonstrated antibody uptake preferentially in viable
      sections of the tumour. The antibody uptake is presumed to be the result mainly
      of binding to the released cytokeratin in and around cells lysed during natural
      cellular death. The monoclonal murine anti-cytokeratin antibody is of potential
      interest in studies aimed at improving the clinical staging of urinary bladder
      cancer.

PMID- 7508237
TI  - Epitope analysis using kinetic measurements of antibody binding to synthetic
      peptides presenting single amino acid substitutions.
AB  - The fine modulation of peptide-antibody interactions was investigated with anti
      peptide monoclonal antibodies recognizing peptide 125-136 of the coat protein of
      tobacco mosaic virus. Nine synthetic peptides presenting single amino acid
      substitutions were selected for detailed analysis on the basis of their
      reactivity in ELISA. Kinetic measurements of the binding of four antibodies to
      these peptides performed with a biosensor instrument (BIAcore, Pharmacia) were
      used to quantify the contribution of individual residues to antibody binding. The
      results showed that even conservative exchanges of some residues in the epitope
      resulted in a small but significant decrease of the equilibrium affinity constant
      due mostly to a higher dissociation rate constant of the monoclonal antibodies.
      Two amino acid residues directly adjacent to the epitope, which appeared to play
      no role when tested by ELISA, were shown to influence the kinetics of binding.
      These data should be useful for computer modelling of the peptide-antibody
      interactions.

PMID- 7508238
TI  - Peptide vaccines incorporating a 'promiscuous' T-cell epitope bypass certain
      haplotype restricted immune responses and provide broad spectrum immunogenicity.
AB  - An ideal peptide vaccine should contain both B- and T-cell epitopes. Recognition
      of antigen by B cells is highly dependent on the three-dimensional conformation
      of the antigen whereas T cells recognize antigen only after it has been processed
      to release a peptide fragment which is bound to the major histocompatibility
      complex (MHC) class II molecule. However, T cells provide 'help' to B cells
      displaying the same processed, MHC-restricted form of the antigen, demonstrating
      that the T-cell response to a protein antigen is under genetic control. Thus,
      strategies for co-inclusion of T cell 'helper' epitopes with the B-cell
      determinant elicit immune responses that are in most cases genetically restricted
      to only one or a few alleles of the MHC with limited activity across divergent
      MHC class II haplotypes. This genetically restricted T cell stimulatory activity
      of peptides is a serious obstacle and consequently such constructs would be of
      limited practical value as a vaccine targeted to a majority of an outbred
      population. In the study described here, we have engineered two peptides to
      encompass the sequences from the universally immunogenic tetanus toxoid (TT)
      epitope and the contraceptive vaccine candidate lactate dehydrogenase C4 (LDH
      C4). We demonstrate the feasibility of using 'promiscuous' T-cell epitopes
      colinearly constructed with a defined B-cell epitope to induce high titer
      antipeptide IgG antibodies specific for native protein antigen LDH-C4 in several
      inbred strains of mice, outbred mice and rabbits. There appears to be a strong
      correlation between the capacity for the hybrid peptides to be stimulatory for
      the corresponding T cells in C57BL/6 (H-2b) and C3H/HeJ (H-2k) mice and their
      ability to be immunogenic. This correlation, however, appears to break down in H
      2d strains of mice since no antibodies were detected in BALB/c and barely
      detectable levels of antibodies in B10.D2 although activated T cells were
      detectable. Conversely, high titers of antipeptide antibodies are elicited in
      some strains (B10.BR (H-2k); C57BL/10 (H-2b) without detectable IL-2 responses.
      Finally, we show that a determinant which was previously restricted to H-2k can
      be rendered immunogenic in H-2b with the 'promiscuous' TT epitope. Thus, certain
      haplotype-restricted immune responses can be bypassed, setting forth the ground
      work for the design of a universal vaccine by broadening the effective response
      in a larger number of individuals typical of the genetically diverse outbred
      human population.

PMID- 7508239
TI  - [Tissue expression of antigenic recognition and intercellular adhesion molecules
      in chronic viral hepatitis].
AB  - OBJECTIVE: To analyze the expression of different HLA class I antigens and cell
      adhesion molecules on frozen liver sections from patients with chronic active
      hepatitis, types B and C. EXPERIMENTAL DESIGN: Liver biopsy samples were divided
      into two parts, one for routine histological examination and another, after snap
      freezing and storing at -80 degrees C, for immunohistochemical analysis. To carry
      out immunoperoxidase and immunofluorescence stainings, a panel of monoclonal
      antibodies specific for HLA class I light (beta 2-microglobulin) and heavy chain
      determinants, and for adhesion molecules such as intercellular adhesion molecule
      1 and lymphocyte function associate antigen-3 was used. PATIENTS:
      Immunohistochemistry was performed in frozen liver biopsy sections from 25
      patients with viral chronic active hepatitis, 10 type B and 15 type C. As
      controls, normal liver samples and liver specimens from patients with cholestasis
      or steatosis were also studied. RESULTS: HLA class I light and heavy chain
      determinants were expressed on hepatocytes, biliary duct epithelium, sinusoidal
      lining cells and lymphocytes from patients and controls; however, the beta 2
      microglobulin conformational epitope was undetectable on hepatocytes from normal
      livers or with cholestasis or steatosis, but clearly positive on hepatocytes from
      patients with hepatitis. In addition, in liver sections from controls no adhesion
      molecules positivity was detected on hepatocytes; by contrast, hepatocytes from
      patients with hepatitis showed markedly enhanced membranous reactivity for both
      adhesion molecules in areas of piecemeal and lobular necrosis. CONCLUSIONS: Virus
      B and C infections could induce an increased hepatocellular expression of HLA
      class I determinants, including the conformational epitope adequate for antigen
      presentation, and cell-cell adhesion molecules. These findings underline the role
      of cell mediated immune reactions in the pathogenesis of hepatic injury in viral
      chronic hepatitis.

PMID- 7508240
TI  - [The plexal hand (involvement of the hand in traumatic lesions of the brachial
      plexus in adults)].
AB  - After spontaneous recovery following brachial plexus injuries, or after nerve
      regeneration following nervous surgery on traumatic brachial plexus, there
      usually is a variable residual distal deficit involving the hand and wrist. This
      deficit is defined by both a functional approach, and its anatomical nervous
      correspondence, in order to predict which motor muscles will be available for
      palliative surgery, and to establish the most reasonable therapeutic plan. Total
      palsy of the hand will only be mentioned, whereas three main presentations of the
      "plexic hand" are of a greater surgical interest and will be detailed: the "wrist
      drop", due to C5 C6 +/- C7 supra-clavicular lesions, the hand presenting with a
      deficit of digit flexion, pinch and intrinsic functions, due to C8 T1 +/- C7
      supra-clavicular lesions, non-standardized deficits due to infra- and retro
      clavicular lesions, whose therapeutic indications and prognosis are closer to
      more classical trunk palsies. The review of 44 "plexic hands" after distal
      palliative surgery indicates the need to modify the fundamental rules of
      tendinous transfer surgery, and suggests new principles properly adapted to the
      surgery of plexic hand palsies.

PMID- 7508241
TI  - [Fresh sections of the flexor tendons of the fingers and thumb. New therapeutic
      trends. Apropos of a clinical series of 77 tendon lesions].
AB  - In flexor tendon surgery, the main concern of hand surgeons in the last two
      decades has been to find an effective and reproducible means to avoid post
      operative adhesions. For most authors, these adhesions were responsible for the
      bad results. Since 1960, a constant progress has been achieved with the progress
      in operative procedures and the better understanding of tendon healing process.
      Post-operative rehabilitation, especially Kleinert's and Duran's active and
      passive methods, have radically transformed the prognosis of fresh tendon
      lesions. In spite of all this progress, zone II tendon injuries are still a
      difficult problem. In this clinical study, we wanted to introduce two new
      orientations in order to improve the overall results, the use of human fibrin
      sealant instead of the epitendinous running suture and an improvement of Duran's
      technique, developed by the Bichat rehabilitation team since 1987. Seventy-seven
      tendon lesions treated according to our technique (55 fingers and 22 thumbs)
      between 1987 and 1991, were reviewed. All the lesions studied were in zone II and
      T II. The mean follow-up is 14.4 months. The evaluation is based on the
      International Federation of Hand Surgery score for fingers, and the Tubiana score
      for thumbs. 74% of fingers and 86% of thumbs were scored as good and excellent.

PMID- 7508243
TI  - [The diagnostic value of arthrography of the wrist in the evaluation of carpal
      ligament injuries: radio-surgical correlations. Apropos of 20 cases].
AB  - Intra-carpal ligament tears lead to radiocarpal arthritis early diagnosis allows
      early treatment. Standard and dynamic X rays are not always able to make the
      diagnosis. In these cases, arthrography of the wrist may give the diagnosis. To
      establish the specificity of this examination we tried to correlate surgical
      findings with arthrographic suspicions. Exact diagnosis was established in 12 out
      of 13 cases of suspected scapholunate ligament tears in 5 out of 6 cases of
      suspected luno-triquetral ligament tear suspicion and none of the 3 cases of
      suspected T.F.C.C. rupture suspicion. Wrist arthrography appears to have a good
      specificity for first row intra-carpal ligament tears. The indication
      arthrography must be discussed with wrist arthroscopy for the diagnosis of long
      term wrist pain after clinical examination and standard and dynamic X rays.

PMID- 7508242
TI  - [Therapeutic possibilities of arthroscopy in chronic painful wrists. Apropos of
      27 cases with 55 arthroscopies].
AB  - 55 arthroscopies of radio- and midcarpal joints of the wrist were performed for
      chronic wrist pain with a difficult diagnosis and/or treatment. None of the
      patients suffered a deterioration and no complications were observed. The results
      were analysed according to Jackson's and Abe's criteria. In the overall series,
      arthroscopy was considered to be beneficial for the diagnosis in 80% of cases and
      for treatment in 49% of cases. Wrist arthroscopy was beneficial in 100% of cases
      for exact evaluation of the lesions of osteoarthritic wrists or wrists with
      intracarpal disorganisation and guided the subsequent therapeutic indications.
      Only 41% of cases obtained a therapeutic benefit from arthroscopy, which
      nevertheless constituted a useful alternative to surgical operations with a long
      postoperative course, allowing rapid return to work. Arthroscopy was beneficial
      for the diagnosis in 66% of chronic painful wrists in which the standard
      radiological and dynamic assessment was normal, by identifying the anatomical
      lesions. Arthroscopy was not beneficial in 34% of cases, corresponding to
      patients with no precise clinical symptoms. Arthroscopy was beneficial for
      treatment in 54% of cases, with complete cure in the majority of cases.

PMID- 7508244
TI  - [Madelung's deformity. A new therapeutic approach].
AB  - Symptomatic Madelung's disease does not respond to conservative treatment and the
      objectives of surgical treatment are essentially to obtain a congruent and
      correctly oriented radio-carpal joint line in order to preserve maximal and
      painless range of joint movement. The various surgical treatment modalities
      proposed to date have been essentially cosmetic and are not sufficient to achieve
      these objectives. The authors propose a new therapeutic approach to this
      deformity: radiolunate and inferior radio-ulnar arthrodesis with Kapandji's
      technique associated with radio-carpal reorientation osteotomy, as required. The
      results obtained in the first four cases are evaluated with a clinical follow-up
      of eighteen months to five years.

PMID- 7508245
TI  - [Protected early mobilization using Levame's device after primary repair of the
      extensor tendons of the hand. Apropos of a series of 88 cases].
AB  - Seventy patients with 88 lesions of the hand extensor apparatus were treated by
      primary repair followed by post-operative mobilisation with a dynamic steel blade
      splint (Levame). Results were good or very good in 97.7% of cases and moderate in
      2.3% of cases for this series of simple lesions from zones 3 to 6. Prognostic
      factors influencing final result and wrist position during splint are discussed,
      the authors leave the wrist free for lesions in zone 3 and 4. Early mobilisation
      is the best treatment for tendinous lesions and a review of the literature
      confirms the validity of the author's choice. In spite of its biomechanical
      deficiencies, this simple technique may be used for non-disciplined patients and
      by non-specialized physiotherapists. For simple lesions of extensor tendons, the
      Levame splint may be considered as a real dynamic protective splint.

PMID- 7508246
TI  - [Lipoma of the fingers].
AB  - Benign tumours of the hand are a common disease, usually corresponding to nodes.
      Other etiologies are less common. Lipomas of the hand are a rare feature,
      especially in the fingers. We present four cases of digital lipomas and a review
      of surgery of lipomas over the past ten years, and of the literature.

PMID- 7508247
TI  - Dietary fructose vs glucose lowers copper solubility in the digesta in the small
      intestine of rats.
AB  - The hypothesis was tested that dietary fructose vs glucose lowers copper
      solubility in the digesta in the small intestine of rats, which in turn causes a
      decreased copper absorption. Male rats were fed adequate-copper (5 mg Cu/kg)
      diets containing either fructose or glucose (709.4 g monosaccharide/kg) for a
      period of 5 wk. Fructose vs glucose significantly lowered copper concentrations
      in plasma and the liver, but did not alter hepatic copper mass. Fructose feeding
      resulted in a significantly lesser intestinal solubility of copper as based on
      either a smaller soluble fraction of copper in the liquid phase of small
      intestinal contents or a lower copper concentration in the liquid phase. The
      latter fructose effect can be explained by the observed fructose-induced increase
      in volume of liquid phase of intestinal digesta. After administration of a
      restricted amount of diet extrinsically labeled with 64Cu, rats fed fructose also
      had significantly lower soluble 64Cu fraction in the digesta of the small
      intestine. Although this study shows that fructose lowered intestinal copper
      solubility, only a slight reduction of apparent copper absorption was observed.
      It is suggested that the fructose-induced lowering of copper status in part
      counteracted the fructose effect on copper absorption at the level of the
      intestinal lumen.

PMID- 7508248
TI  - Studies on metal resistance system in Kluyveromyces marxianus.
AB  - Through preliminary plate tests, Kluyveromyces marxianus was found to be much
      more resistant to toxic heavy metals compared to a CUP1R strain of Saccharomyces
      cerevisiae. Specific growth rate and maximum dry weights affected by increasing
      metal concentrations were determined to obtain precise patterns of resistance.
      Metal biosorption was also monitored during the course of growth in synthetic
      media containing respective metals at 0.5 mM final concentration. Although Zn-
      and Co-binding was negligible, as much as 90% of silver, 60% of copper, and 65%
      of cadmium were found to be absorbed by the end of active growth. Analysis of the
      protein profiles of S. cerevisiae and K. marxianus on metal exposure suggested
      constitutive production of metallothionein in K. marxianus. Furthermore, a
      smaller protein synthesized by K. marxianus on induction by silver or cadmium
      accounts for the high resistance of the organism to these metals.

PMID- 7508250
TI  - Plasma and liver selenium levels in the rat during supplementation with 0.5, 2,
      6, and 15 ppm selenium in drinking water.
AB  - Plasma and liver selenium of Wistar rats were determined after 1, 3, and 6 mo
      supplementation with 0.5, 2, 6, or 15 ppm selenium as sodium selenite in drinking
      water. Plasma selenium was not different from control values at additional intake
      of 0.5 ppm but increased above usual levels at higher intakes. A highly
      significant correlation was observed between the total quantity of selenium
      ingested and plasma selenium after 1 mo treatment (r = 0.99, p < 0.01), but was
      less pronounced after 3 and 6 mo (0.94, p < 0.05, and 0.78, p < 0.05,
      respectively). The decrease in plasma selenium with time of treatment was more
      pronounced at higher intakes. There was also a highly significant correlation
      between total selenium intake and liver selenium concentration (r = 0.99, p <
      0.01) after 1 mo of treatment, but this time liver selenium did not change with
      time, and the correlation remained highly significant throughout the
      investigation. Liver selenium therefore appears as a more sensitive and more
      representative measure of selenium intake than plasma selenium. Most supplements
      did not affect body weight and survival of animals, except when the diet was
      supplemented with 15 ppm for 6 mo; however, alterations in biochemical parameters
      concerning lipid status and hepatic function were observed at levels above 2.0
      ppm.

PMID- 7508249
TI  - The responses of hepatic monooxygenases of guinea pig to cadmium and nickel.
AB  - When Cd (3.58 mg CdCl2.H2O/kg, ip) was administered to male guinea pigs 72 h
      prior to sacrifice, the metal significantly inhibited the aniline 4-hydroxylase
      (AH) (16%), ethylmorphone N-demethylase (EMND) (26%), and aminopyrine N
      demethylase (AMND) (18%) activities and cytochrome P-450 (12%) and cytochrome b5
      (10%) levels. Cd did not alter the hepatic microsomal heme level. Cd, however,
      significantly increased the hepatic microsomal p-nitroanisole O-demethylase (p
      NAOD) (53%) activity. When Ni (59.5 mg NiCl2 x 6H2O/kg, sc) was administered to
      the guinea pigs 16 h prior to sacrifice, the metal significantly depressed AH
      (49%), p-NAOD (66%), EMND (47%), and AMND (37%) activities, and cytochrome P-450
      (15%), cytochrome b5 (24%), and microsomal heme (28%) levels. For the combined
      treatment, animals received the single dose of Ni 56 h after the single dose of
      Cd and then were killed 16 h later. In these animals, significant inhibitions
      were noted in AH (51%), EMND (47%), and AMND (30%) activities, and cytochrome P
      450 (15%), cytochrome b5 (26%), and microsomal heme (30%) compared to those of
      controls. In the case of p-NAOD activity, the influence was in favor of Ni, i.e.,
      the inhibition was about 61% by the combined treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508251
TI  - Hyperbaric hyperoxia exaggerates respiratory membrane defects in the copper
      deficient rat lung.
AB  - Scanning (SEM) and transmission electron microscopy (TEM) were used to examine
      the effect of dietary copper deficiency and hyperbaric hyperoxia, alone and in
      combination, on lung structure. Male, weanling Sprague-Dawley rats were fed a
      copper-deficient (CuD, 0.2 microgram/g) or copper-adequate diet (CuA, 5.1
      micrograms/g). After 35-41 d on their respective diets, rats from each group were
      placed inside a pressure vessel kept at 27 degrees C under one of two pressure
      protocols. Air controls were maintained at 1 atm for 75 min. Rats exposed to
      oxygen were maintained at 1 atm of air plus 3 atm of oxygen for 1 h and then
      decompressed for 15 min. Under SEM, none of the treated lungs (CuD, CuA-O2
      exposed, or CuD-O2 exposed) showed abnormal lung morphology from the conducting
      bronchioles down to the alveoli. Copper-deficient red blood cells were abnormally
      shaped. Under TEM, CuA-O2-exposed lungs showed thicker respiratory membranes,
      especially basement membranes and endothelial cells, and alveolar Type II cells
      having more than the usual number of surfactant vacuoles. CuD lungs also showed
      thicker endothelial and basement membrane components of the respiratory membrane,
      but normal looking Type II cells. CuD-O2-exposed lungs showed greatly thickened
      respiratory membranes and severe disruption of both endothelium and basement
      membrane and, judging by the increased number of nuclei per field, an increase in
      the number of both Type I and Type II cells. We conclude that copper deficiency
      enhances the damage caused by O2 toxicity, an effect that may be caused by
      reduced antioxidant status.

PMID- 7508254
TI  - Health situation in the Americas--1992.

PMID- 7508253
TI  - Plasma trace element (Se, Zn, Cu) concentrations in maternal and umbilical cord
      blood in Poland. Relation with birth weight, gestational age, and parity.
AB  - Selenium (Se), copper (Cu), and zinc (Zn) concentrations were determined in
      plasma of 64 mothers at delivery, 58 nonpregnant women, 64 neonates, and 12
      infants, aged 2-12 mo. Se and Zn concentrations in mothers at delivery were
      significantly lower, and Cu higher than in nonpregnant women. Mean Se and Cu
      concentrations in newborns were statistically lower than those in mothers at
      delivery, and Zn and Cu concentrations in preterm infants (n = 13) were
      significantly higher than in fullterm infants (n = 51). Maternal parity had no
      significant influence on the distribution of plasma trace element levels. No
      significant differences were observed in Se and Zn levels in maternal and cord
      blood plasma according to birth weight, contrary to maternal Cu concentration.
      Significant correlations were found between maternal and cord blood Se content,
      and between maternal plasma Cu concentration and birth weight of neonates.

PMID- 7508255
TI  - Association of malignant melanoma and germ cell tumour.

PMID- 7508256
TI  - A comparative study of the cytotoxicity of skin irritants on cultured human oral
      and skin keratinocytes.
AB  - The cytotoxicity of irritants on human oral and skin keratinocyte culture models
      was compared. Keratinocytes were exposed to sodium lauryl sulphate and
      benzalkonium chloride at concentrations of 10(-4)-10(-7) M for 24 h. Cytotoxicity
      was evaluated by changes in mitochondrial metabolic activity (MTT assay) and
      plasma membrane integrity (LDH leakage). Our results showed that oral and skin
      keratinocytes are equally sensitive to the irritants tested. There were marked
      similarities in susceptibility between each cell type cultured from six
      individuals. The immunohistochemical staining pattern of both cell types
      resembled that of the basal cell. These observations suggest that the skin
      keratinocyte culture model may be useful in evaluating the cytotoxicity of agents
      which are irritants on either the skin or oral mucosa.

PMID- 7508257
TI  - Methodological aspects of DNA image cytometry in normal bone marrow smears.
AB  - The possibility of using DNA image cytometry in hematological material was
      evaluated in 27 Feulgen stained normal bone marrow smears. The 95% normal limits
      of DNA index (DI) determined separately for each cell population in bone marrow
      were 0.89-1.15, 0.93-1.09 and 0.92-1.12 for blasts, granulocytes and lymphocytes,
      respectively. The mean DI for blasts, granulocytes and lymphocytes was 1.02, 1.01
      and 1.02, respectively. In the blasts population the mean percentage of cells in
      S+G2/M phase was 38.1% (S.D. 12.9%, range 14.3-65.6%), whereas the corresponding
      values for granulocytes and lymphocytes were below 1%. Calculation of DI and
      G0/G1 C.V. obtained in bone marrow smears subjected to Feulgen hydrolysis (5 N
      HCl, 22 degrees C) for different periods of time revealed the presence of a
      plateau of results between 60 and 120 min for all of the cell types. The
      intraobserver and interobserver reproducibility was confirmed by duplicate
      measurements of each subpopulation (P > 0.05). A comparison of DI and G0/G1 C.V.
      using smears from the same donors stained with the Feulgen method either straight
      away or after destaining from May-Grunwald-Giemsa confirmed that destained smears
      can be used, provided applying appropriately prepared reference cells. We
      conclude that image cytometry can be used reliably to analyze DNA content in
      hematological material.

PMID- 7508252
TI  - Effects of cesium on cellular systems.

PMID- 7508258
TI  - Tracheal tumours: could treatment be better?
AB  - The rarity of primary tracheal tumours makes research into their natural history
      and treatment very difficult. Diagnosis is often made too late for cure.
      Palliation has improved with the introduction of laser resection, brachytherapy
      and stents. Squamous cell carcinoma may have a better prognosis in the trachea
      than in the lung. It has been assumed that surgery is the treatment of choice and
      up to 50% of the trachea can be resected with modern techniques. However, several
      of the largest surgical series have used mostly post-operative radiotherapy and
      really represent the results of combined therapy. High dose radiotherapy may
      achieve cure in some cases. Prospective studies of the relative merits of surgery
      and radiotherapy are urgently needed. The British Thoracic Society Research
      Committee is launching a national study at the present time.

PMID- 7508259
TI  - The impact of prostatic manipulation upon serum PSA in patients with
      adenocarcinoma of the prostate.
AB  - A prospective study was carried out to evaluate the possible impact of prostatic
      manipulation upon the serum prostate specific antigen (PSA) in a cohort of 98
      patients prior to treatment of adenocarcinoma of the prostate. The PSA levels
      were assessed before and 1 hour after examination under anaesthetic (EUA). There
      were 87 complete pairs of observations. In 71 patients there was either no change
      (n = 2) or a rise (n = 69); in 16 there was a fall. The median change in the
      group as a whole was +2.0 ng/ml (range -10.8-36.2). The average percentage rise
      in PSA was 42.3% (median 17.4%) with the largest percentage changes seen in those
      with the lowest initial PSA levels, with those in the range < 4 ng/ml exhibiting
      a 66.7% rise and those with > 35 ng/ml a 3.2% rise (median values). An attempt is
      made to express these changes in a clinical sense by allocating patients (pre
      EUA) to one of four ranges of values as follows, 0-4.0, 4.1-10.0, 10.1-35.0 and >
      35 ng/ml and observing the frequency with which they climbed to a higher category
      after EUA. This occurred in 23%, 50%, and 15% of patients respectively. The
      changes in PSA were statistically significant but their clinical significance
      might depend upon the clinical setting. Thus no patient would have had their
      management changed as a result of such a rise in PSA, but this might assume
      greater importance during the months of follow-up after radiation therapy, where
      a rise in PSA after prostatic manipulation might result in undue patient anxiety
      and unnecessary investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508260
TI  - Maternal alpha-fetoprotein levels in multiple pregnancies.

PMID- 7508262
TI  - In vitro selection of RNA aptamers specific for cyanocobalamin.
AB  - RNA receptors (aptamers) capable of specifically binding cyanocobalamin (vitamin
      B12) have been isolated by in vitro selection from a pool of 5 x 10(14) RNAs of
      random sequence. After eight rounds of selection by affinity chromatography and
      enzymatic amplification, the pool was dominated by two sequences. The major
      sequence, comprising 60% of the pool, was studied further. It was found to bind
      vitamin B12 in solution with a dissociation constant (Kd) of approximately 320 +/
      90 nM and to bind cobinamide dicyanide with a Kd of 8.8 +/- 0.5 microM. The
      aptamer does not detectably bind adenosylcobalamin (coenzyme B12). The selection
      was conducted in 1 M LiCl, and binding is dependent on the presence of high
      concentrations of Li+ but independent of Mg2+. To define the binding site for
      cyanocobalamin, a second cyanocobalamin-binding selection was carried out using a
      pool of sequences derived from the major aptamer sequence randomized at a level
      of 30%. The sequence data from this selection revealed a 31-base highly conserved
      region, on the basis of which was synthesized a smaller aptamer of 35
      nucleotides. This small aptamer binds cyanocobalamin in solution with a Kd of 88
      +/- 19 nM and cobinamide dicyanide with a Kd of 20 +/- 9 microM. This aptamer has
      the highest affinity yet reported for a small molecule ligand. A number of
      covarying positions were found in the conserved region of the sequences from this
      second, mutagenized pool selection. On the basis of these data, an unusual
      pseudoknot secondary structure is proposed for the aptamer. Chemical modification
      protection experiments are consistent with this structure and have demonstrated
      that the RNA undergoes a conformational change upon binding its ligand. Possible
      contacts with the cyanocobalamin have also been mapped. A third selection was
      carried out in which the salt specificity of the aptamer was changed from LiCl to
      NaCl plus MgCl2. Sequence analysis of the final round pool of RNAs from this
      selection revealed several conserved changes from the original vitamin B12
      aptamer sequence.

PMID- 7508261
TI  - NMR determination of the structures of peroxycobalt(III) bleomycin and
      cobalt(III) bleomycin, products of the aerobic oxidation of cobalt(II) bleomycin
      by dioxygen.
AB  - The oxidation of Co(II) bleomycin A2 by dioxygen leads to two products, HO2
      Co(III) bleomycin A2 (form I) and Co(III) bleomycin A2 (form II). 1H NMR chemical
      shift assignments for protons of both forms have been made by two-dimensional NMR
      spectral techniques. The chemical shifts of protons throughout forms I and II
      differ from each other and from apobleomycin A2. NOESY spectra reveal a number of
      intermediate and long-range 1H-1H couplings within the metal-binding domain,
      between the metal-binding domain and the peptide linker, which connects it and
      the DNA-binding region of the molecule, and, in form I, between the DNA- and
      metal-binding domains. Molecular dynamics calculations were carried out based on
      the NOESY results and an adjustable square pyramidyl ligand geometry around
      Co(III) composed of nitrogen atoms of the primary and secondary amine groups,
      pyridine (N5), and amide and imidazole (N1) of the hydroxyhistidine residue. In
      form I, the bithiazole group folds back across the square pyramid forming a
      compact structure. Although this conformational feature was not observed in form
      II, the peptide linker between the metal- and DNA-binding domains in both species
      shows extensive folding based on a large number of intramolecular interactions.

PMID- 7508263
TI  - Human intestinal cell line Caco-2: a useful model for studying cellular and
      molecular regulation of biotin uptake.
AB  - The mechanisms of enterocyte and molecular regulation of biotin uptake are poorly
      understood. An intestinal cell line processing the transport characteristics of
      native intestinal cells is highly desirable to investigate the finer details of
      the cellular processing and molecular regulation of biotin transport. In the
      present study, we investigated the uptake of the water-soluble vitamin biotin by
      a human intestinal cell line Caco-2. Uptake of both low (4 nM) and high (20
      microM) concentrations of biotin by confluent monolayers of Caco-2 cells was
      appreciable and linear for up to 10 min of incubation. Replacement of Na+ in the
      incubation medium with other monovalent cations--K+, choline, Li+ and NH4(+)-
      caused a significant inhibition of biotin uptake; a relatively lesser inhibition
      was seen with Li+. Initial rate of uptake of biotin was temperature-dependent and
      saturable as a function of concentration at 37 degrees C but not at 4 degrees C.
      The Vmax and apparent Km of the temperature-dependent saturable process were 520
      pmol/mg protein per min and 9.5 microM, respectively. The addition of unlabeled
      biotin and the structural analogue desthiobiotin to the incubation media caused a
      significant inhibition of the uptake of [3H]biotin. The inhibitory effect of
      desthiobiotin was competitive in nature with an inhibition constant (Ki) of 41
      microM. Biocytin, on the other hand, was a weak inhibitor and biotin methyl ester
      and diaminobiotin did not have any effect. Pretreatment of Caco-2 cells with the
      monovalent cation ionophore gramicidin and the Na+, K+(-)ATPase inhibitor ouabain
      caused significant inhibition of biotin uptake. Pretreatment with the K+
      ionophore valinomycin did not affect biotin uptake. Using the 'Activation
      Method', the stoichiometric ratio of biotin- to Na+ coupling was found to be 1:1.
      Growing confluent Caco-2 cells in a biotin-deficient environment resulted in
      rapid up-regulation of biotin transport with a marked increase (258%) in the Vmax
      of biotin uptake. These findings demonstrate that biotin uptake by Caco-2 cells
      is via a carrier-mediated system. This system is temperature-dependent, driven by
      Na(+)-gradient and is regulated by the substrate level. These in-vitro findings
      are very similar to and further confirm previous findings in human and animal
      studies and dispute other findings previously reported for Caco-2 cells; the
      present study also demonstrates the suitability of this system for further
      characterization of the cellular and molecular regulation of biotin uptake.

PMID- 7508264
TI  - Identification of an IgE-binding determinant of the major allergen Myr p I from
      the venom of the Australian jumper ant Myrmecia pilosula.
AB  - The structure of the single allergenic determinant of the major ant venom
      allergen, Myr p I from the Australian jumper ant Myrmecia pilosula has been
      determined by inhibition studies with synthetic peptides. A 14 amino-acid C
      terminal peptide sequence has been shown to constitute this determinant. Half
      maximal inhibition of binding of ant venom-specific IgE antibodies to the native
      venom was obtained with this peptide at a concentration of 5 x 10(-8) M. This
      allergenic determinant was invariant for all ant venom-allergic subjects tested
      whose IgE antibodies recognized this allergen.

PMID- 7508265
TI  - Carrier-protein-mediated enhancement of fatty-acid binding and internalization in
      human T-lymphocytes.
AB  - Albumin and alpha-fetoprotein (AFP) are members of a multigene family which also
      includes vitamin-D-binding protein. Previous work in our laboratory has provided
      experimental support for the suggestion that the entry of unsaturated fatty acids
      into growing, normal and neoplastic cells may be regulated by AFP. In the actual
      study we have examined the role of human serum albumin (HSA) as a carrier
      protein, when compared to AFP, on the uptake (binding and internalization) of
      fatty acids by resting and PHA-activated human lymphocytes. Radioiodinated human
      HSA and tritiated oleic and arachidonic acids were used under different
      experimental conditions to follow the binding of the protein and fatty acids (FA)
      to cells. Time-course uptake at 4 degrees C of HSA and of oleic and arachidonic
      acids bound to HSA (FA/HSA molar ratio = 1) by either resting or activated T
      lymphocytes exhibited a steady state of binding. The amount of FA bound was much
      greater than the corresponding amount of HSA, suggesting that T-lymphocytes bear
      distinct binding sites for albumin and fatty acids. A saturable process of FA
      binding was observed at constant unbound FA concentration in the incubation
      medium when the HSA-to-FA molar ratio was fixed at 1 and the concentrations of
      both HSA and FA were increased simultaneously. This saturable component of
      binding reflects an intrinsic regulatory effect of HSA, probably operating
      throughout the interaction of the protein with specific cell receptors. At
      varying unbound FA concentrations, binding curves showed two distinct components:
      a non-linear portion which could indicate the presence of a saturable process
      operating at low concentrations of unbound, free FA, followed by a second part
      which increased linearly with the concentration of unbound FA. The amount of FA
      bound at 4 degrees C and bound and internalized at 37 degrees C by both types of
      cell was considerably higher in the presence than in the absence of carrier
      proteins. On the contrary, carrier proteins were without effect on the
      distribution pattern of internalized oleic or arachidonic acid. Taken together,
      these observations suggest that: (i) the binding and entry of FA into cells is
      enhanced by the two carrier-proteins at low concentrations of free, unbound fatty
      acids in the vicinity of the cell surface, and (ii) fatty-acid uptake seems
      regulated by a dual-receptor mechanism involving HSA and/or AFP receptors as well
      as plasma-membrane FA-binding proteins.

PMID- 7508266
TI  - The effect of arachidonic acid on the hydroosmotic action of vasopressin in frog
      urinary bladder.
AB  - In experiments on frog urinary bladder it was found that 23 nM arginine
      vasopressin (antidiuretic hormone, AVP), 10 min after addition, increased the
      content of free arachidonic acid (AA) in bladder tissue from 18.6 +/- 1.2 to 33.3
      +/- 3.9 ng/mg protein. The exogenous AA (10(-8) - 10(-5) M) added to the serosal
      Ringer solution did not change the basal level of osmotic water flow, but
      significantly inhibited the hydroosmotic effect of 23 nM AVP in a dose-dependent
      manner. The inhibitory effect of AA was not eliminated in the presence of 1
      microM indomethacin, 1 microM nordihydroguaiaretic acid, 100 microM ketoconazole,
      nor if the nonmetabolized analog of AA, eicosatetraynoic acid (1 microM), was
      used instead of AA. AA inhibited only the action of vasopressin, but had no
      effect on osmotic water flow induced by 2 mM cAMP + 50 microM 3-isobutyl-1
      methylxanthine or 20 microM forskolin. These data suggest that AA is another
      phospholipid-derived messenger, which modulates the hydroosmotic action of
      vasopressin in frog urinary bladder at a point prior to cAMP formation.

PMID- 7508267
TI  - Basic fibroblast growth factor-Pseudomonas exotoxin chimeric proteins; comparison
      with acidic fibroblast growth factor-Pseudomonas exotoxin.
AB  - We have constructed growth factor-toxin chimeric molecules composed of basic
      fibroblast growth factor (bFGF) and two different binding mutant forms of
      Pseudomonas exotoxin termed bFGF-PE40 and bFGF-PE4E KDEL. The chimeric molecules
      were expressed in Escherichia coli and localized to both inclusion bodies and the
      spheroplast cytoplasm. The bFGF-toxin fusion protein that was isolated and
      purified from inclusion bodies was 3-fold more active in inhibiting protein
      synthesis than that purified from spheroplast cytoplasm. Immunoreactivity of
      purified bFGF-toxin fusion protein to anti-bFGF antibodies was similar to that of
      native bFGF, as determined by ELISA analysis. A variety of carcinoma cell lines
      were sensitive to bFGF-PE40 and bFGF-PE4E KDEL, including H3396 (breast), Hep G2
      (hepatocellular), and A431 (epidermoid). The concentration of chimeric toxin that
      inhibited protein synthesis by 50% (EC50) was 110, 70, and 18 ng/mL for bFGF-PE40
      and 15, 1, and 18 ng/mL for bFGF-PE4E KDEL. In comparison with fusion-toxins
      composed of acidic fibroblast growth factor (aFGF) and either PE40 or PE4EKDEL,
      bFGF-PE40 and bFGF-PE4E KDEL were similarly cytotoxic on most cell lines tested.
      Human aortic smooth muscle cells were sensitive to both bFGF and aFGF toxin
      fusion proteins. However, human aortic endothelial cells were sensitive to the
      bFGF-toxins but were resistant to both aFGF-toxin forms. Time course studies
      showed that bFGF-PE40 needed a 4-6-h exposure to target cells for peak inhibition
      of protein synthesis on both MCF-7 and A431 cells, while aFGF-PE40 was almost
      fully active within a 2-h incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508271
TI  - Urinary amylase isoenzymes and amylase polymorphism variants in families with
      diabetes mellitus type 1.
AB  - Insulin-dependent diabetes mellitus type 1 is an autoimmune disease of pancreatic
      beta-cells with a certain genetic predisposition that is not yet clear. In spite
      of the confirmed association of diabetes mellitus type 1 with several HLA
      haplotypes it is considered that other loci must be involved for total genetic
      susceptibility to the disease. The relationship of insulin deficiency and
      decreased pancreatic amylase activity suggests that insulin itself is a direct
      activator of amylase gene expression. Endocrine pancreatic function was monitored
      by the indirect non-invasive method of urinary pancreatic amylase activity
      determination (expressed in percentage of total amylase activity) in diabetic
      children, their parents, healthy sisters and brothers, and in a separate group of
      women with diabetes type 1 of over 20 years duration. The incidence of hereditary
      amylase polymorphism variants in these subjects was also ascertained. Decreased
      pancreatic amylase activity in urine (under 58%) was found to be a characteristic
      trait in diabetics, and a susceptibility trait in asymptomatic family members.
      Normal pancreatic amylase activity (66.7 +/- 5.4%) is rare in diabetic patients
      type 1, but may be seen as a favourable prognostic trait, representing resistance
      to diabetic complications. The results support the suggestion that hereditary
      predisposition to the disease is inherited from the father rather than the
      mother, and that heterozygous amylase polymorphism variants protect their
      carriers against diabetes mellitus type 1.

PMID- 7508268
TI  - (6-Maleimidocaproyl)hydrazone of doxorubicin--a new derivative for the
      preparation of immunoconjugates of doxorubicin.
AB  - The (6-maleimidocaproyl)hydrazone of doxorubicin was synthesized and conjugated
      to several mAbs, including chimeric BR96, via a Michael addition reaction to
      thiol-containing mAbs. DTT reduction of disulfides present in the mAb was a
      reliable and general method for generating a consistent number of reactive SH
      groups. The conjugates, after purification by Bio-Beads, were free of unreacted
      linker and/or doxorubicin. All conjugates released doxorubicin under acidic
      conditions that mimic the lysosomal environment, while they were relatively
      stable at neutral pH. BR96 conjugates showed antigen-specific cytotoxicity.

PMID- 7508270
TI  - Glycated LDL concentrations in non-diabetic and diabetic subjects measured with
      monoclonal antibodies reactive with glycated apolipoprotein B epitopes.
AB  - The potential importance of the non-enzymatic glycation of low density
      lipoproteins (LDL) in atherogenesis and in the accelerated atherosclerosis
      associated with diabetes is well recognized. However, it has been difficult to
      evaluate LDL glycation in the clinical setting because of the lack of suitable
      methods. To approach this problem, we produced monoclonal antibodies, designated
      ES12, that recognize glycated apolipoprotein B epitopes in the LDL complex in
      human plasma. Here we report the use of these antibodies in a competitive enzyme
      linked immunosorbent assay (ELISA) to measure glycated LDL concentrations in
      plasma from non-diabetic and diabetic subjects. In this assay, glycated LDL in
      the soluble phase inhibits binding of the ES12 antibody to glycated LDL
      immobilized to microtitre wells, whereas other glycated proteins and non-glycated
      LDL do not compete. A linear dose-response relationship for 10-125 ng glycated
      LDL per well allows the construction of standard curves, from which the
      concentration of glycated LDL in human plasma can be determined. The mean
      concentration of glycated LDL in samples from non-diabetic subjects was 21.8 +/-
      0.9 mg/l, increasing to 40.8 +/- 2.6 mg/l in samples from patients with type II
      diabetes, comprising 1.9-4.8% and 3.2-14.8%, respectively, of total
      apolipoprotein B. Glycated LDL concentrations in samples from diabetic patients
      correlated positively and significantly with other indices of glycaemic status.
      The results indicate that circulating glycated LDL, which may have diagnostic and
      pathophysiologic importance, is increased in diabetes with attendant
      hyperglycaemia. The results further indicate that the described monoclonal
      antibody-based competitive ELISA affords a simple and reproducible method for
      quantitative measurement of glycated LDL.

PMID- 7508269
TI  - Oriented and covalent immobilization of target molecules to solid supports:
      synthesis and application of a light-activatable and thiol-reactive cross-linking
      reagent.
AB  - Light-dependent oriented and covalent immobilization of target molecules has been
      achieved by combining two modification procedures: light-dependent coupling of
      target molecules to inert surfaces and thiol-selective reactions occurring at
      macromolecule or substrate surfaces. For immobilization purposes the
      heterobifunctional reagent N-[m-[3-(trifluoromethyl)diazirin-3-yl]phenyl]-4
      maleimidobutyr amide was synthesized and chemically characterized. The
      photosensitivity of the carbene-generating reagent and its reactivity toward
      thiols were ascertained. Light-induced cross-linking properties of the reagent
      were documented (i) by reacting first the maleimide function with a thiolated
      surface, followed by carbene insertion into applied target molecules, (ii) by
      photochemical coupling of the reagent to an inert support followed by
      thermochemical reactions with thiol functions, and (iii) by thermochemical
      modification of target molecules prior to carbene-mediated insertion into surface
      materials. Procedures mentioned led to light-dependent covalent immobilization of
      target molecules including amino acids, a synthetic peptide, and antibody-derived
      F(ab') fragments. Topically selective, light-dependent immobilization was
      attained with the bifunctional reagent by irradiation of coated surfaces through
      patterned masks. Glass and polystyrene served as substrates. Molecular
      orientation is asserted by inherently available or selectively introduced
      terminal thiol functions in F(ab') fragments and synthetic polypeptides,
      respectively.

PMID- 7508272
TI  - Determination of the catalytic activity of phospholipase A2: E. coli-based assay
      compared to a photometric micelle assay.
AB  - Phospholipase A2 activity in human sera was determined of the basis of the E.
      coli assay and compared to a photometric micelle assay. The E. coli assay is
      based on the hydrolysis of phospholipids from [1-14C]oleic acid-labelled E. coli
      biomembranes. In the photometric assay the phospholipase A2 acts on mixed
      phospholipid micelles. The amount of fatty acid produced is quantitated in a
      subsequent photometric assay by coupling in the reaction to the coenzyme A
      metabolism. The E. coli membranes are essentially resistant to other lipases in
      human sera, i.e. lipoprotein lipases, hepatic triacylglycerolipase or pancreatic
      lipase and thus a very specific substrate for the phospholipase A2 of human
      serum. The photometric assay, though, is susceptible to other lipases in human
      serum. The ratio of [1-14C]oleic acid to released total fatty acids served as the
      basis for the calculation of the true enzymatic activity. The assay closely
      correlated with the photometric assay based on mixed micelles in the higher
      ranges of phospholipase A2 activity, but not in the normal range. The sensitivity
      is higher by at least two powers of 10. The human serum phospholipase A2 strongly
      preferred E. coli membranes as substrate to the mixed micelles containing
      phosphatidylcholine/phosphatidylethanolamine. In conclusion, the modified
      phospholipase A2 assay based on E. coli membranes is a sensitive, specific,
      reliable, and convenient method for the measurement of phospholipase A2 activity
      in human sera. The photometric assay suffers from low sensitivity but has the
      advantage of practicability in a normal routine laboratory, including the
      amenability to automation.

PMID- 7508273
TI  - Distribution characteristics of immunosuppressants FK506 and cyclosporin A in the
      blood compartment.
AB  - Using two representative immunosuppressants, FK506 (FK) and cyclosporin A (CyA),
      of which the mechanism of pharmacological action is the same although there is a
      great difference in the pharmacological intensity, the distribution
      characteristics were studied in both in vivo and in vitro experiments using rat,
      dog, and human blood. Blood samples were fractionated by means of sedimentation
      in Ficoll-Paque, and the drug contents in the diluted plasma fraction,
      erythrocyte fraction, and lymphocyte fraction were measured by an HPLC method. FK
      distributes to the lymphocyte fraction to a level about three times greater than
      that of CyA, while CyA distributes to the erythrocyte fraction to a level ten
      times that of FK. The distribution pattern of these fractions was independent of
      the drug concentration and species after correcting the drug concentration in
      each fraction with the blood drug concentration. The uptakes of FK and CyA in the
      isolated lymphocytes obtained from the rat spleen and human peripheral blood were
      also studied. The amount of FK taken up by the spleen lymphocytes is five times
      greater than that of CyA. In the case of the uptake study using human peripheral
      blood lymphocytes, the concentration of FK in the lymphocyte is 100-fold higher
      than that of CyA. This difference in the lymphocyte level between the two
      immunosuppressants is thought to be one of the reasons why FK is more potent than
      CyA, a difference of about 100-fold in the in vitro pharmacological study and
      about tenfold in the in vivo organ transplantation experiments.

PMID- 7508274
TI  - The structural barrier of absorptive mucosae: site difference of the permeability
      of fluorescein isothiocyanate-labelled dextran in rabbits.
AB  - The permeability of fluorescein isothiocyanate-labelled dextran (FD, M.W. 4400
      71,200) across nasal, buccal, duodenal, jejunal, ileal, colonic, and rectal
      mucosae excised from rabbits has been measured to estimate the structural barrier
      of absorptive mucosae using Ussing-type diffusion chambers. The permeability
      coefficient of FD in all these mucosae decreased with increasing molecular
      weight. The rank order of FD permeability did not always correlate with the
      electrical resistance of the mucosae. Among components of the small intestine
      (duodenum, jejunum, ileum) and the large intestine (colon, rectum), however, the
      rank order of FD permeability corresponded to the magnitude of the electrical
      resistance in each instance; the upper colonic mucosa showed the highest
      permeability, especially in FD of low molecular weight, and permeability of the
      rectal mucosa was lowest except for the duodenal mucosa. The nasal mucosa showed
      the lowest electrical resistance and the highest permeability of those studied,
      suggesting that it has a leaky structural barrier.

PMID- 7508275
TI  - It is possible to increase skeletal muscle fibre number in utero.
AB  - The administration of porcine somatotropin (pST) to pregnant sows during early
      gestation (day 10 to 24) induced the formation of significantly more muscle
      fibres in the semitendinosus muscle of the fetuses, representing a higher growth
      capacity of skeletal muscle. The pST-treatment during late pregnancy (day 80 to
      94) accelerated the development of the fetus resulting in higher body weights and
      advanced stage of maturity at birth.

PMID- 7508276
TI  - Modulation of glomerular arteriolar tone by nitric oxide synthase inhibitors.
AB  - The inhibition of nitric oxide production has been shown to reduce RBF. The
      effects of the nitric oxide synthase inhibitors, N omega-nitro-L-arginine and NG
      monomethyl-L-arginine, on afferent and efferent arterioles isolated from rabbit
      kidneys were examined. Under basal conditions, N omega-nitro-L-arginine (10(-7)
      to 10(-3) M) had no effect on efferent arteriole lumen diameter but caused a 40%
      decrease in the lumen diameter of afferent arterioles. In afferent and efferent
      arterioles precontracted with norepinephrine, N omega-nitro-L-arginine and NG
      monomethyl-L-arginine (3 x 10(-4) M) markedly attenuated the vasorelaxant effects
      of the endothelium-dependent vasodilator acetylcholine. In both arterioles, the
      inhibitory effect of N omega-nitro-L-arginine on acetylcholine-induced relaxation
      could be reversed by L- but not D-arginine (10(-3) M). However, N omega-nitro-L
      arginine had no effect on the relaxation produced by the endothelium-independent
      vasodilators prostaglandin E2 (afferent) and dopamine (efferent). These
      observations demonstrate that under the in vitro conditions used in this study,
      afferent arterioles but not efferent arterioles synthesize and release nitric
      oxide in the basal state. However, both arterioles release nitric oxide in
      response to an endothelium-dependent vasodilator. The results of this study
      provide further evidence for an important role of nitric oxide in the regulation
      of renal hemodynamics.

PMID- 7508277
TI  - Anesthetic management for a palliative surgical procedure in a 72-year-old
      patient with tetralogy of Fallot.

PMID- 7508278
TI  - XVIth Congress of the Society of Biomechanics. Lille, France, 8-9 November 1991.
      Proceedings.

PMID- 7508279
TI  - The effect of nifedipine and verapamil on rhythmic contractions of human isolated
      ureter.
AB  - The effect of calcium antagonists nifedipine and verapamil on spontaneous
      rhythmic contractions of human isolated ureter obtained from donor subjects
      undergoing kidney transplantation was investigated in comparison with a
      nonsteroidal antiinflammatory drug indomethacin. Stop-times i.e. the time
      elapsing from application, were determined for each drug. The rank order of
      potency at 10(-8) and 10(-7) M concentrations of the drugs was: nifedipine >
      verapamil > or = indomethacin. However, no significant difference of the stop
      times was observed at 10(-6) M concentration of the drugs tested. The rhythmic
      contractions were re-activated by PGF2 alpha after stoppage with indomethacin but
      not with nifedipine or verapamil. These results suggest that not only endogenous
      PG synthesis but also an influx of calcium from the extracellular space is
      responsible for the spontaneous rhythmic activity of human ureter. The beneficial
      effects of using calcium antagonists in the treatment of ureteric colic is
      discussed.

PMID- 7508280
TI  - Neonatal red blood cell lysis induced by hypertonic low ionic strength media.
AB  - Human neonatal red cells (placental blood) incubated in hypertonic sucrose media
      showed a significative lytic process in a relatively short time interval. The
      addition of sodium chloride into the sucrose media reduced the extent of
      hemolysis. In contrast, the addition of calcium chloride enhanced the hemolysis
      in these red cells. Calcium-membrane components complex formation that
      destabilize membrane's bilayer structure would explain the calcium effect above
      mentioned (on account of the low ionic strength media used and exposed fixed
      negative charges) This study intends to clarify, in neonatal red cells, the
      relation between surface charges and cellular stability.

PMID- 7508281
TI  - Biochemical composition and fatty acid content of zooplankton from tropical
      lagoon for larval rearing.
AB  - Zooplankton samples were collected from the indigenous tropical brackish water
      lagoon during the wet monsoon (January and February 1990) and the dry monsoon
      (April and May 1990). The dominant copepod species in the zooplankton community
      comprising of Oithona sp (especially O. nana and O. robusta) accounted for more
      than 70% of the zooplankton in January and was gradually replaced by other
      zooplanktonic species later in the dry season. The lipid contents in zooplankton
      varied from 0.18 to 1.04% wet weight or 1.14 to 5.92% dry weight respectively.
      The major fatty acid contents of the zooplankton showed high concentration of
      14:0, 16:0, 18:1, 20:5 omega 3 and 22:6 omega 3 especially in the wet season. It
      also contained high omega-3 highly unsaturated fatty acid series necessary for
      the growth of commercial fish larvae. It has a better food value than the
      normally use food organism, brine shrimp; thus reflecting its potential use as
      food organism for fish larval rearing.

PMID- 7508282
TI  - Steroid assays in saliva: a method to detect plasmatic contaminations.
AB  - Plasmatic and salivary levels of six steroid hormones in adult males and females
      are given and compared to the data of the literature. These steroids are:
      cortisol (F), dehydroepiandrosterone (DHA) and its sulphate (DHAS),
      androstenedione (A), testosterone (T) and 11 beta OH androstenedione (OHA). The
      salivary assay of the last compound is an original. The correlations between
      salivary and plasmatic values are presented and confirm that this method is a
      reliable alternative for hormonal investigations. From these data and from those
      of the literature, the salivary versus plasmatic ratio are calculated. From the
      fact that high concentrations of DHAS in saliva generally stem from blood
      contamination, we derive a method to estimate the amount of this contamination
      and its impact on other steroids measured on the same saliva sample.

PMID- 7508283
TI  - Changes induced by hypothyroidism in insulin secretion and in the properties of
      islet plasma membranes.
AB  - This work was aimed at elucidating the effect of thyroid function on the
      physiology and biochemistry of the islet-cell population within the endocrine
      pancreas. To this end, we performed a comparative study of the physiochemical
      properties of islet-cell membranes and of the dynamics of glucose-induced insulin
      secretion in isolated pancreatic islets prepared from euthyroid i.e. control (C),
      hypothyroid (H), and thyroxin-supplemented hypothyroid (HT) rats. H rats were
      obtained by injecting normal rats with 131iodine, while HT rats consisted of H
      rats treated with thyroxin (T4). Insulin secretion was studied in isolated islets
      perifused with 3.3 and 16.6 mM glucose. Physicochemical properties of the
      partially purified islet plasma membranes were assessed by measurements of
      fluorescence polarization with the fluorophore 1,6-diphenyl-1,3,5-hexatriene
      (DPH) as a lipidic molecular probe. Insulin output during either the first or
      second phase of insulin secretion in H islets was significantly lower than in C
      islets. The slope of the curve in the second phase of insulin secretion was also
      lesser in H than in C islets, suggesting an additional defect in their velocity
      of hormone release. T4 administration of H rats reversed the decrease in insulin
      output to the range found in C islets but was incapable of correcting the defect
      in the hormone-secretion velocity. Several changes were found in the
      physicochemical properties of the membranes obtained from H islets as compared to
      C islets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508284
TI  - Effects of folic acid and methotrexate on arginase activity in regenerating rat
      liver tissue.
AB  - Arginase (L-arginine-ureidohydrolase, EC 3.5.3.1) catalyses the hydrolysis of
      arginine to ornithine and urea. Its primary metabolic role is to remove the
      excess of ammonia through synthesis of urea. Ornithine, as a product of arginase
      reaction can be used for synthesis of polyamines. Rapid tissue growth after
      partial hepatectomy is accompanied by an increase in biosynthesis of polyamines.
      The aim of this study was to examine the importance of arginase in regenerating
      liver after partial hepatectomy and to investigate the influence of folic acid
      and methotrexate on arginase activity on this model of compensatory growth. It
      was established that arginase activity was significantly reduced in regenerating
      rat liver tissue at different time intervals after partial hepatectomy.
      Administration of folic acid to hepatectomized rats led to inhibition of arginase
      activity. Administration of methotrexate after hepatectomy increased the arginase
      activity.

PMID- 7508285
TI  - Adrenal response to acute stress in mammillary medial nuclei lesioned rats.
AB  - In view of the inhibitory influence of Mammillary Medial Nuclei, pars lateralis
      (MMN) on corticoadrenal activity, experiments were conducted in order to
      determine whether these nuclei are involved in the control of adrenal response to
      ether stress. In bilateral MMN lesioned rats, prestress plasma corticosterone
      concentration (C) is significantly higher than that in sham lesioned animals.
      Acute stress produced a significant C increase in both, sham and lesioned rats,
      being this increase lower in lesioned animals. After exposure to ether vapors.
      adrenal concentration of norepinephrine was similar in lesioned and control
      animals. Whereas, adrenal epinephrine concentration was significantly higher in
      lesioned rats than that found in the sham lesioned ones. This study demonstrates
      that the integrity of MMN is not essential for adrenal response to acute stress.

PMID- 7508286
TI  - Diminished myofibrillar sensitivity to calcium produced by simultaneous
      superfusion of cAMP and phosphodiesterases inhibitors in toad (Bufo arenarum
      Hensel) ventricle.
AB  - Experiments were performed in EGTA-skinned trabeculae from toad ventricle to
      explore the effects of the cAMP on calcium sensitivity of the contractile system.
      10(-3) M of the cAMP derivative dibutyryl cAMP (dcAMP) failed to affect calcium
      sensitivity of chemically skinned ventricular trabeculae. 10(-5) M of the
      phosphodiesterase inhibitor isobutylmethylxantine (IBMX) produced a significant
      shift to the left of the tension-pCa relationship. The computed half maximally
      activating pCa (pCa50) were 6.32 +/- 0.03 and 6.40 +/- 0.01 in the absence and
      presence of IBMX respectively, (P < 0.05). Simultaneous perfusion of 10(-5) M
      IBMX and 10(-3) M dcAMP suppressed the leftward shift of the tension-pCa curve
      induced by IBMX (pCa50: 6.33 +/- 0.04 and 6.33 +/- 0.05 for control and IBMX
      respectively). Perfusion with the phosphodiesterase inhibitor milrinone (10(-5)
      M), did not produce any significant changes in the tension-pCa relationship.
      Simultaneous perfusion of 10(-5) M milrinone and 10(-3) M dcAMP significantly
      shifted to the right the tension-pCa curve. The computed pCa50 were 6.32 +/- 0.02
      and 6.23 +/- 0.03 under control conditions and in the presence of dcAMP plus
      milrinone respectively (P < 0.05). In agreement with what has been described in
      mammalian heart, the results indicate that in amphibian ventricle, cAMP produced
      a decrease in the calcium sensitivity of the contractile proteins that is only
      evident in the presence of phosphodiesterase inhibitors. It is suggested that
      this decrease in myofilament sensitivity to calcium may be one of the mechanisms
      by which beta-agonists enhance myocardial relaxation in the amphibian heart.

PMID- 7508287
TI  - Diurnal rhythm of the in vivo acetate metabolism to CO2 and nonsaponifiable
      lipids by neonatal chick.
AB  - The in vivo incorporation of acetate into nonsaponifiable lipids was studied in
      different tissues from 14-day-old chick. Total nonsaponifiable lipids (nmol/30
      min/g tissue) were mainly synthesized in testicles and liver. The in vivo CO2
      production from acetate by 1-day-old chick did not exhibit diurnal variations.
      However, in 14-day-old chick, a maximal value was observed in the middle of the
      light period, while a minimal value was found 9 h after the start of the dark
      period. No significant diurnal differences were detected in the in vivo acetate
      incorporation into nonsaponifiable lipids by liver and duodenal mucosa from 1-day
      old chick. Nevertheless, a clear diurnal rhythm was found in liver and duodenal
      mucosa from 14-day-old chick, but not in brain and kidney from animals of the
      same age. Distribution of radioactivity from (1-14C)acetate among the different
      constituents of the nonsaponifiable fraction has been also studied at 3-h
      intervals. Cholesterol was the major sterol formed from acetate by chick liver at
      any time of day. In duodenal mucosa and kidney, maximal values in the percentage
      of cholesterol synthesized were observed during the light period.

PMID- 7508288
TI  - Melanin quantitation from human erythrocytes; interference by haeme derivatives.
AB  - Precipitates were obtained by 6 N HCl hydrolysis of human erythrocytes and
      subsequent extractions with ethanol-ether 1:1 and with tetrahydrofuran. The mean
      quantity of these precipitates (n = 16) was 16.60 +/- 1.60 (standard deviation)
      mg/ml, (15.09 +/- 1.45 mg/g) and from saline washed erythrocyte samples (n = 8)
      16.65 +/- 0.73 mg/ml, (15.14 +/- 0.67 mg/g). A large part of these precipitates
      (about 74%) is associated with haemoglobin (in average 12.34 mg/ml). Melanins
      account for the difference (16.60-12.34) = 4.26 mg/ml, approximately 8.7% of
      haemoglobin-free erythrocyte solids. Precipitates from red cells, and from
      haemoglobin produced similar UV-VIS and IR spectra. The precipitates from
      haemoglobin are mainly derivatives of haeme (about 97%); the remaining
      approximately 3% are melanins from globin. The total melanins are about 1.3% of
      haeme-free solids of erythrocytes. Precipitation from the erythrocytes with 6 N
      HCl was also achieved in practically complete argon atmosphere, and similar
      quantities were obtained as those in air with the same UV-VIS and IR spectra.
      Since granules or solid particles are not found in the cytoplasm of normal human
      erythrocytes, we conclude that soluble melanins are present. Small amounts of
      melanins can be present in the membranes as well, since the precursors of
      melanins: norepinephrine, epinephrine are present in these membranes.

PMID- 7508289
TI  - Human neonatal red blood cells. An experimental model for the study of calcium
      activated potassium channel refractoriness.
AB  - To study some characteristics of calcium-activated potassium channels free from
      plasma membrane lipid perturbations, neonatal red blood cells were selected. To
      this end, cells not previously treated (ATP depletion and/or reversible lysis)
      were exposed to the ionophore A23187 in a NO3 medium with calcium. The net efflux
      of potassium from the cells was studied. Preincubation in a medium devoid of
      potassium induced a significant decrease only in the rate constant of potassium
      flux. The data suggest that, in the absence of plasma membrane lipid impairment,
      changes in internal sites reactivity with calcium ions of channel proteins would
      be involved in the refractoriness. This would be at variance with channel density
      modifications.

PMID- 7508290
TI  - Variations in lactate apparent clearance during rest and exercise in normal man.
AB  - The purpose of this study is to present a simple kinetic model for the study of
      the lactate metabolism. This model based on pharmacokinetic theory, does not
      require labelled molecules and yields a finer approach to lactate metabolism than
      does a simple observation of blood lactate concentration. The variations in
      parameter values have been studied in six male subjects after intensive exercise
      (385 W, 110 rpm and 1 min) (IE) followed by three different recovery periods:
      passive recovery (RE), moderate exercise (ME) and heavy exercise (HE). Blood
      lactate concentration was measured prior to IE and during the first hour of
      recovery. After mathematical treatment, the results show that the apparent
      clearance increases 2.83 +/- 0.76 fold from RE to ME and 1.96 +/- 0.61 fold from
      RE to HE. The steady state blood lactate concentration induced by the intensity
      of recovery (La(ss)) increases slightly (1.53 +/- 0.37 fold) from RE (1.40 +/-
      0.36 mmol.l-1) to ME (2.04 +/- 0.32 mmol.l-1). Then La(ss) increases markedly
      (3.78 +/- 0.91 mmol.l-1) during HE (2.81 +/- 0.78 fold the La(ss) value at RE).
      The ratio between the apparent rates of lactate production (F"K0) during RE, ME
      and HE was calculated. F"K0 increases in a linear way versus intensity of
      exercise recovery. It was concluded that in the human: 1) the blood lactate
      concentration is not an accurate indicator of lactate production, 2) in our
      experiment, the apparent lactate production is a linear function of exercise
      intensity and 3) the abruptly increasing blood lactate concentration at a high
      level of exercise intensity is due to a decrease in apparent clearance.

PMID- 7508291
TI  - [The hyperammonemia of exercise; value of automatic measurement].
AB  - Ammonia blood level (NH3) was measured during maximum exercise performed on
      cycloergometer, in 11 patients. NH3 measurements through an automatic chemical
      method (whole blood) were compared to those of the enzymatic reference method
      (plasma). Automatic analysis made it possible to quickly obtain [NH3] values,
      that were highly correlated with those of the enzymatic method (P < 0.001).
      Plasma [NH3] may be calculated from the following equation, where it is expressed
      versus [NH3] obtained with the automatic method (c anal): [NH3] mumol.l-1 =
      0.795. [c] anal.microgram.dl-1 + 5.446.

PMID- 7508292
TI  - A voltage-clamp study of calcium currents in neurons freshly isolated from the
      dorsal root ganglion of adult rats.
AB  - Calcium currents were studied in a preparation of freshly isolated neurons of the
      dorsal root ganglion (DRG) of adult rats using the whole-cell voltage-clamp
      technique in conditions of minimal current flow through sodium and potassium
      channels. A low-threshold (LT) and a high-threshold (HT) current were
      distinguished on the basis of a different potential of activation. Both currents
      also showed differences in their peak amplitude, their distribution among the
      cells, their kinetics, their steady-state inactivation curve and their
      sensitivity to cadmium. Comparison of the properties of both currents with the
      known properties of calcium currents in DRG neurons from immature animals
      indicates a slower rate of inactivation of the LT-current in the adult DRG
      neuron. The calcium entry blocker flunarizine (10 microM) caused a negative shift
      of the steady-state inactivation curve of the inactivating component of HT
      current, an effect which suggests voltage-dependent inhibition.

PMID- 7508294
TI  - The Cell: Structure and Function. Proceedings of the X National Meeting of the
      GIC. September 28-October 1, 1993. Abstracts.

PMID- 7508295
TI  - Italian Society for the Study of Connective Tissues. XIVth National Congress.
      Genova, Italy, 8-9 October 1993. Abstracts.

PMID- 7508293
TI  - Tenascin is associated with articular cartilage development.
AB  - The roles of tenascin in cartilage development and function remain unclear. Based
      on the observation that tenascin is particularly abundant at the epiphyseal
      extremities of developing cartilaginous models of long bones in chick and mouse
      embryo, we tested the hypothesis that tenascin is involved in articular cartilage
      development. Immunofluorescence analysis revealed that tenascin was first
      localized in the cell condensation region of Day 4 chick embryo limb buds, where
      the cartilaginous models form. With further development, tenascin gene expression
      became indeed restricted to the articular cap of the models. Tenascin persisted
      in the articular cartilage of postnatal chickens but appeared to decrease with
      age. The protein was also abundant in embryonic and adult tracheal cartilage
      rings which, like articular cartilage, persist throughout postnatal life. Similar
      patterns of tenascin expression were seen in mouse. Using monoclonal antibodies
      to avian tenascin variants, we found that the bulk of articular cartilage
      contained the shortest tenascin variant (Tn190), whereas the largest variant
      (Tn230) was present in tissues associated or interacting with articular cartilage
      (ligaments and meniscus). The protein and its mRNA, however, were undetectable in
      growth plate cartilage undergoing maturation and endochondral ossification. This
      inverse correlation between chondrocyte maturation and tenascin production was
      corroborated by the finding that tenascin gene expression decreased markedly
      during maturation of chondrocytes in culture and during formation of a secondary
      ossification center within the articular cap in vivo. Thus, tenascin is
      intimately associated with the development of articular cartilage and other
      permanent cartilages whereas absence or reduced amounts of this matrix protein
      characterize transient cartilages which undergo maturation and are replaced by
      bone.

PMID- 7508297
TI  - Tolonium chloride as a mucous membrane dye.

PMID- 7508298
TI  - Comment: intravenous streptomycin.

PMID- 7508296
TI  - The Gly/Arg-rich (GAR) domain of Xenopus nucleolin facilitates in vitro nucleic
      acid binding and in vivo nucleolar localization.
AB  - Epitope-tagged Xenopus nucleolin was expressed in Escherichia coli cells and in
      Xenopus oocytes either as a full-length wild-type protein or as a truncation that
      lacked the distinctive carboxy glycine/arginine-rich (GAR) domain. Both full
      length and truncated versions of nucleolin were tagged at their amino termini
      with five tandem human c-myc epitopes. Whether produced in E. coli or in Xenopus,
      epitope-tagged full-length nucleolin bound nucleic acid probes in in vitro filter
      binding assays. Conversely, the E. coli-expressed GAR truncation failed to bind
      the nucleic acid probes, whereas the Xenopus-expressed truncation maintained
      slight binding activity. Indirect immunofluorescence staining showed that myc
      tagged full-length nucleolin properly localized to the dense fibrillar regions
      within the multiple nucleoli of Xenopus oocyte nuclei. The epitope-tagged GAR
      truncation also translocated to the oocyte nuclei, but it failed to efficiently
      localize to the nucleoli. Our results show that the carboxy GAR domain must be
      present for nucleolin to efficiently bind nucleic acids in vitro and to associate
      with nucleoli in vivo.

PMID- 7508300
TI  - Primary papillary psammomatous adenocarcinoma of the umbilicus.
AB  - The histological and ultrastructural features, as well as the immunoreactivity of
      one case of uncommon primary papillary and psammomatous adenocarcinoma of the
      umbilicus are studied in the present work. The observations have been undertaken
      in a nine-year follow-up, and have included the primitive tumour, two local
      recidives, and inguinal lymphatic metastasis on two occasions. Papillary
      structures, numerous psammoma bodies, as well as weak and focal positive
      reactions to CEA and cytokeratin were present in all the tumours. Since these
      features and their ultrastructural characteristics were identical to primary
      papillary serous neoplasias of the peritoneum and ovarium, the hypothesis of an
      origin in coelomic remnants is considered.

PMID- 7508299
TI  - Entero-cytolysin (EC) from Vibrio cholerae non-O1 (some properties and pore
      forming activity).
AB  - A thermolabile extracellular entero-cytolysin (EC) from Vibrio cholerae non-O1
      was purified by ammonium sulphate fractionation, DE-52 cellulose ion exchange
      chromatography, gel-filtration on Ultrogel AcA-44 and high performance liquid
      chromatography on a Mono Q. The purified EC had a molecular weight of 63 kD and
      an isoelectric point of 6.2. It was not inactivated by cholesterol or 5,5'-dithio
      bis(2-nitrobenzoic acid), nor activated by dithiothreitol. EC had no
      immunological cross-reactivity with cholera toxin. The EC caused fluid
      accumulation in the intestines of infant rabbits, death of mice by intravenous
      injection, and increased vascular permeability in the paw oedema test in mice. V.
      cholerae non-O1 EC lysed erythrocytes from various species and cultured cells
      (CHO, L-929, L-41, HEp-2, Vero, MDCK and BHK-21). In contrast to cholera toxin,
      EC caused crude destruction of target cells. The EC caused hemolysis by a colloid
      osmotic mechanism due to the formation of hydrophilic pores of 1.8-2.0 nm
      diameter in the cell membrane. This EC also was able to open pores in lipid
      membranes. The induced channels were anion-selective and had a diameter of 1.8
      2.0 nm.

PMID- 7508301
TI  - Immunohistochemical characterization of transplantable rat squamous cell
      carcinoma (FF-6) in skin and thymus.
AB  - FF-6 is a transplantable squamous cell carcinoma which originally arose in the
      facial skin of a DA rat. It was established after maintaining the tumor in the
      subcutaneous tissue or peritoneal cavity of DA rats conventionally for over 30
      generations. When the soybean-sized original FF-6 tumor was transplanted
      subcutaneously, it became an oval, hard, whitish, solitary and thumb-head-sized
      nodule within one month. After intraperitoneal transplantation of FF-6, it formed
      many nodules ranging from miliary to thumb-head size, which adhered and/or
      metastasized to many abdominal organs. When FF-6, cut into small pieces, was
      injected into the lower lip, the tumor grew bigger in situ, and metastasized to
      regional lymph nodes. Histologically, FF-6 was characterized as a well
      differentiated squamous cell carcinoma, showing positive staining with anti
      keratin, anti-laminin, anti-collagen type IV, anti-fibronectin and UB-14
      antibodies. This transplantable tumor may be useful for analyzing the mechanisms
      of proliferation and metastasis of squamous cell carcinoma in vivo, and the host
      defence mechanism in rats, as well as being a suitable model of human squamous
      cell carcinoma.

PMID- 7508302
TI  - Late events in the migrative behaviour of the retinal ganglion cells. A Golgi
      study in the chick retina.
AB  - The final displacement of the prospective ganglion neurons toward the ganglion
      cell layer (GCL) has been analyzed in chicken embryos during days 8 and 9 of
      incubation with the help of the Golgi method and computer-assisted image
      processing. Our findings indicate that some ganglionar soma are still located in
      the inner nuclear layer (INL) while others pierce the inner plexiform layer
      (IPL), exhibiting morphological adaptation of their perikaryon. The changing
      morphology of these delayed retinal ganglion neuroblasts seems to be due to the
      late translocation of the cell perikaryon to the GCL. This late migrative
      displacement of the ganglionar population is discussed in relation to the
      presence of displaced ganglion cells of Dogiel.

PMID- 7508303
TI  - Immunohistochemical study of intracranial cysts.
AB  - We present the immunohistochemical study of 11 cases of intracranial cysts: two
      extraventricular ependymal cysts, three colloid cysts of the third ventricle,
      four extraventricular choroidal cysts and two Rathke's cleft cysts. Antibodies
      against glial fibrillary acidic protein (GFAP), cytokeratins (AE1, CK5D, AE3), S
      100 protein, epithelial membrane antigen (EMA), vimentin, neuron specific enolase
      (NSE), neurofilaments protein (NF) and prealbumin, were used. The epithelium of
      choroidal cysts, showed strong immunoreactivity for Prealbumin and cytokeratins,
      similar to the normal choroid plexus epithelium. The ependymal cysts showed
      epithelial immunoreactivity for GFAP and S-100, both glial markers expressed by
      the normal ependymal epithelium. On the contrary, the epithelial wall of colloid
      cysts and Rathke's cleft cyst, expressed epithelial markers (cytokeratins and
      EMA) but no neuroepithelial markers, with a immuno-phenotype similar to that of
      other cysts of endodermal nature. This finding supports the neuroepithelial
      origin for choroid and ependymal cysts, and an endodermal nature for colloid and
      Rathke's cleft cysts. We conclude that these immunohistochemical markers are
      useful in the differential diagnosis of intracranial cysts.

PMID- 7508304
TI  - Studies of activated microglia and macrophages in lumbosacral spinal cord
      following an intraperitoneal injection of 6-aminonicotinamide into adult rats.
AB  - The anterior horns of the lumbosacral segment of the spinal cord in rats showed
      an extensive lesion following an intraperitoneal administration of 6-amino
      nicotinamide (6-AN). Neuronal chromatolysis was observed in some of the large
      efferent neurons 1-7 days after the injection of 6-AN. The capability in their
      uptake of fluorogold and its retrograde transport was comparable to those in the
      normal rats. Small neurons presumably internuncial cells underwent degeneration.
      8 weeks after 6-AN injection, all the surviving neurons appeared normal. 1 day
      after 6-AN injection microglial cells appeared activated as evidenced by the
      hypertrophy and expansion of their processes. A large number of macrophages were
      observed in the lesioned site 7 days after the administration of 6-AN. The
      activated microglia and macrophages showed intense immunoreactivity with the
      monoclonal antibody OX-42. The immunoreactivity declined with time so that by 4
      weeks after the injection of 6-AN very weak immunoreactivity was seen on some
      very branched cells. A similar pattern of immunoreactivity was observed with the
      monoclonal antibodies OX-18 and OX-6. It was concluded from this study that
      neuronal chromatolysis and neuronal degeneration induced the expression of CR3
      receptors (marked by OX-42) and MHC encoded antigens (marked by OX-18 and OX-6)
      in activated microglia and macrophages. With time the immunoreactivity decreased
      so that by 4 weeks after the administration of 6-AN only faint immunoreactivity
      was observed on some branched cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508305
TI  - Lymphocyte interactions with the extracellular matrix of malignant cells in
      vitro: a morphological and immunocytochemical study.
AB  - The interactions of lymphocytes with the glycosaminoglycans-protease-membrane
      extracellular matrix, produced by mixed cell cultures of normal with malignant
      cell clones, were examined. Pre-activated and activated heterologous peripheral
      lymphocytes were used. Co-cultures of activated lymphocytes with all cell types
      used, formed identical cell nodules. Histology of cell nodules showed that
      activated lymphocytes were cytolytic to pure normal or malignant cell clones. On
      the contrary, lymphocytes in nodules with mixed cell clones (normal with
      malignant cell clones) or embryonic cells, underwent degeneration changing the
      fusiform type tumor nodule into the adenoid type. The adenoid type cell nodule
      consisted of cells with high nuclear to cytoplasm ratio and mitotic activity. In
      addition, leukocyte common antigen was deposited in the extracellular matrix and
      on the cell membrane of target tumor cells. Pre-activated lymphocytes, in mixed
      cell cultures, failed to lyse the target tumor cells and underwent abnormal cell
      divisions, producing subsets similar to nuclear vlimata, which remained attached
      to the extracellular matrix. The morphological and immunocytochemical
      observations of lymphocytes were discussed and attributed to the presence of the
      specific extracellular matrix of glycosaminoglycans-protease-membranes.

PMID- 7508306
TI  - Morphology and neurochemistry of the pelvic, and paracervical ganglia.
AB  - Autonomic ganglia are relays in the distribution of nerve fibres in the
      peripheral nervous system. In the pelvis there are local ganglion formations in
      the pathway of nerve fibres to and from pelvic viscera and vasculature: in
      rodents these are the male anterior major pelvic ganglion and the female
      paracervical ganglion (Frankenhauser's ganglion). They are unusual in that they
      contain both sympathetic and parasympathetic ganglion cells. Homologous
      formations occur in humans. Since the best studied examples of these ganglionic
      formations are rodent ganglia the latter are reviewed in terms of their gross
      anatomy, cell morphology and immunohistochemistry. The synaptology, and
      neurotransmitter and neuropeptide contents of the neuronal perikarya and nerve
      terminals, of the ganglia are discussed in relation to the concepts of
      coexistence and chemical coding in autonomic ganglia in general. The neuropeptide
      content of the nerve fibres projecting to their visceral targets is described and
      discussed in functional terms. Conclusions are drawn with respect to the
      contributions made by study of these ganglia to further understanding of the
      organisation of the autonomic nervous system in general. The possible link
      between the autonomic nervous system and the endocrine system is discussed with
      respect to control of pelvic visceral activities.

PMID- 7508307
TI  - Molecular development of immune deposits and proteinuria in Heymann nephritis.

PMID- 7508308
TI  - Regulation of tubular transport via ion channels.

PMID- 7508309
TI  - Safety of dextran in relation to other colloids--ten years experience with hapten
      inhibition.
AB  - OBJECTIVE: The effects of hapten inhibition with dextran 1 (molecular weight:
      1,000 D, Promit), which is in use since 1982 for the prevention of severe dextran
      induced anaphylactic reactions (DIAR) caused by immune complexes, were studied.
      DESIGN: Spontaneous reports to the manufacturer and to the WHO database INTDIS
      regarding adverse reactions to clinical dextran after preinjection of dextran 1
      and to dextran 1 alone were collected from 1983 to 1992. During this period a
      total of 5.1 million doses of dextran 1 were sold in 15 countries. INTERVENTIONS:
      Analysis of pre- and post-reaction titers of dextran-reactive antibodies (DRA)
      was made in most Scandinavian reports. RESULTS: The incidence of severe DIAR
      (grades III-V) to clinical dextran after the prophylactic use of hapten
      inhibition was approximately 1/200,000 patients receiving dextran 1. In Sweden,
      where reporting of severe adverse drug reactions is mandatory, the incidence was
      approximately 1/70,000, indicating a 35-fold reduction. Only 2 fatal reactions
      were reported, an incidence of 1/2.5 million doses, indicating a 90-fold
      reduction. Both these occurred in patients with extremely high titers of DRA.
      Side effects to dextran 1, mostly mild, were reported in approximately 1 case per
      100,000 doses. These side effects were not antibody mediated. CONCLUSIONS: The
      above findings, together with other recent safety profile data, suggest that
      dextran with hapten inhibition has possibly become the safest plasma substitute
      in current clinical practice.

PMID- 7508310
TI  - Is chrysotile asbestos exposure a significant health risk to the general
      population?
AB  - The main unresolved issues concerning environmental exposure to chrysotile
      asbestos of the general population are discussed. A review of the results of the
      measurement of airborne chrysotile fibres in buildings is presented showing that
      the results have been consistently low with the exception of buildings with
      damaged friable asbestos-containing material. Quantitative risk assessments are
      presented indicating that the lifetime risk is small compared to many other
      environmental risks. Possible adverse health effects of paraoccupational
      exposures in the case of high domestic airborne asbestos levels cannot be
      excluded. Both on the basis of electron microscopy analyses of asbestos exposures
      at locations with heavy traffic, and the very shallow slopes in the exposure
      response relationships for increased lung cancer risk, the conclusion is drawn
      that exposure to airborne asbestos-containing friction materials has not been
      proven to pose a significant health risk to the general population. Reviewing
      animal ingestion studies published and all the available epidemiological studies
      related to asbestos in drinking water, the conclusion is drawn that the
      carcinogenic risk in the general population is low even in the case of drinking
      water containing elevated concentrations of chrysotile asbestos.

PMID- 7508311
TI  - Calcium channels and calcium-gated potassium channels at the frog neuromuscular
      junction.
AB  - Two mechanisms which regulate transmitter release by regulating Ca2+ entry in the
      presynaptic nerve terminal were studied at the frog neuromuscular junction (nmj).
      First, the location of Ca2+ channels in relation to transmitter release sites
      and, second, the regulation of Ca2+ entry by Ca(2+)-gated potassium (gKca)
      channels. Ca2+ channels were disclosed using fluorescent omega-conotoxin GVIA
      (omega-CgTX) which blocks transmitter release and Ca2+ entry at the frog nmj.
      Ca2+ channels were located in bands spaced at regular intervals of 1 micron. The
      omega-CgTX labeling was removed following mechanical displacement of the
      presynaptic terminal after collagenase digestion. The bands of omega-CgTX
      staining matched almost perfectly the staining of cholinergic receptors with
      fluorescent alpha-bungarotoxin (alpha-BuTX) and therefore must be located at the
      active zone. The role of gKca channels in the regulation of transmitter release
      was assessed using charybdotoxin (ChTX) which blocks gKca channels of large and
      intermediate conductances. Application of ChTX (2-20 nM) induced a two-fold
      increase in transmitter release which was prevented when a membrane permeant Ca2+
      buffer (DMBAPTA-AM) was introduced prior to the toxin application. The Ca2+
      buffer by itself caused a reduction in transmitter release. Nerve-evoked Ca2+
      entry in the presynaptic terminal, detected with the fluorescent indicator fluo3,
      was increased following gKca channel blockade by ChTX. The Ca(2+)-gated K+
      channels may function to limit the duration of the presynaptic action potential
      and thus limit Ca2+ entry.

PMID- 7508315
TI  - Control of meningococcal disease.

PMID- 7508314
TI  - [Incidence of the form and caliber of urethral resistance. Evaluation for a
      normal masculine urethra and in cases of obstruction due to prostatic
      hypertrophy].
AB  - Certain forms of benign prostatic hypertrophy are associated with a reduction of
      the calibre of the prostatic urethra of the median lobe, a defect of
      infundibulisation of the bladder neck and a dilated appearance of the bulbar
      urethra. The objective of this study was to verify whether hydrodynamic arguments
      could be used to confirm the concept that defective infundibulisation of the
      bladder neck is directly responsible for an obstructive syndrome or via a
      reduction in the calibre of the bladder neck orifice. More generally, this study
      was designed to quantify the distribution of resistance to flow along the normal
      urethra and to define the role of cervicoprostatic and urethral deformities in
      the obstruction associated with benign prostatic hypertrophy. Urodynamic studies
      are unable to answer this question, as the instantaneous urethral resistance is
      evaluated globally by the Pressure-Flow relation. The authors performed
      morphological analysis to divide the urethra into simple hydraulic segments for
      which the corresponding pressure drop coefficients were calculated. These
      coefficients constitute an approach to segmental resistance to flow and can be
      used to quantify changes in shape observed on voiding urethrography or
      ultrasonography. Digital analysis of voiding urethrographies showed that, under
      normal conditions, urethral resistance was regularly distributed along the
      urethra and essentially depended on friction of the urethral wall. In the case of
      benign prostatic hypertrophy, even with a median lobe, the increase in the
      pressure drop coefficients was due to a reduction in the calibre of the bladder
      neck orifice and prostatic urethra. Cervical deformities appeared to be minimally
      obstructive, according to urodynamic parameters, if they were not associated with
      a reduction in the calibre of the bladder neck orifice.

PMID- 7508313
TI  - [Can we do better than surgery in the treatment of benign prostatic hypertrophy?
      Results after 10 years in endoscopic resection and adenomectomy in urination and
      sexual disorders].
AB  - Surgery is considered to be the reference treatment for obstructive benign
      prostatic hypertrophy (NPH). Transurethral resection of the prostate (TURP) and
      suprapubic prostatectomy are the operations most frequently performed by
      urologists. However, little information is available concerning the long-term
      results of this surgery. In order to assess the long-term efficacy, we recalled
      618 consecutive patients operated for benign prostatic hypertrophy between 1979
      and 1982 (390 by TURP and 228 by suprapubic prostatectomy (SP). 167 patients were
      reviewed and investigated, 150 had died and 301 were lost to follow-up. Ten years
      after the operation, 85% of the patients reviewed had good or satisfactory
      micturition and 72% of them were satisfied, regardless of the technique used. In
      80% of patients, no complementary procedure was required to ensure urinary
      comfort. However, the effects of this surgery on sexual function were
      considerable, as one half of patients reporting sexual intercourse before the
      operation reported a deterioration of sexual function after the operation.
      Lastly, long-term morbidity affected 10 to 41% of patients and 9 to 12% of them
      were reoperated. Although, overall, surgery gave excellent results at 10 years,
      15% of patients did not derive any benefit from the procedure. It is therefore
      important, in the future, to more clearly define the indications for surgery and
      the place of noninvasive treatments. At the present time, young subjects wishing
      to preserve their sex life may benefit from noninvasive first-line treatments,
      provided their quality of life is sufficiently altered by the severity of the
      urinary symptoms.

PMID- 7508312
TI  - Roles for arachidonic acid and GTP-binding proteins in synaptic transmission.
AB  - Using synapses which form between somata of Helisoma neurons in cell culture we
      have studied the presynaptic regulation of synaptic transmission. GTP-binding
      proteins play important roles in regulating synaptic transmission through their
      actions on calcium currents, potassium currents and secretory apparatus.
      Heterotrimeric G proteins continuously regulate the amount of transmitter
      released at the synapse. By interacting with the arachidonic acid second
      messenger system they modulate potassium channels, and could potentially control
      the secretory apparatus. Perturbations of the rab protein system did not affect
      action potential-evoked transmission, but did control the frequency of miniature
      inhibitory postsynaptic currents. This is consistent with the involvement of this
      type of GTP-binding protein in the control of secretory apparatus, but suggests
      that rab proteins are not used to regulate the amount of transmitter released at
      the synapse. Using the Helisoma cellular system which permits direct access to
      the presynaptic site of transmitter release we are going on to study further the
      role of arachidonic acid, Go, Gi and rab proteins on the regulation of the
      secretory apparatus.

PMID- 7508316
TI  - The Peters'-Plus syndrome: description of 16 patients and review of the
      literature.
AB  - Peters'-Plus syndrome is characterized by Peters' anomaly, a typical face, cleft
      lip and palate, short limb dwarfism, and developmental retardation. We report the
      follow-up of six patients in the original report, 10 yet unreported patients, and
      review 26 patients that have been reported in the literature. The spectrum of the
      syndrome is broadened by data from affected sibs which indicate that a wider
      range of anterior chamber cleavage disorders may be present, a cleft lip or
      palate need not be present, and developmental retardation may be mild or even
      absent. An increased foetal loss in families with Peters'-Plus syndrome may
      indicate intrauterine death of some foetuses affected by the syndrome. The
      pattern of inheritance is autosomal recessive.

PMID- 7508317
TI  - Kivlin syndrome and Peters'-Plus syndrome: are they the same disorder?
AB  - Manifestations of Peters'-Plus syndrome include Peters' anomaly, short stature,
      small hands, mental retardation, abnormal ears and cleft lip and palate. 'Kivlin'
      syndrome is a similar disorder involving Peters' anomaly, short stature, short
      limbs, delayed development, facial clefting in some, ear abnormalities and a
      characteristic facial appearance attributable mainly to a 'cupid's bow' shape of
      the upper lip. Two new adult cases of Peters'-Plus are described, and follow-up
      information on a previously reported case of 'Kivlin' syndrome is presented. The
      two syndromes are reviewed and it is concluded that they are the same autosomal
      recessively inherited disorder, which we suggest should be called Peters'-Plus
      syndrome.

PMID- 7508318
TI  - A distinctive syndrome of brachycephaly, deafness, cataracts and mental
      retardation.
AB  - A boy with brachycephaly without craniosynostosis, raised intracranial pressure,
      deafness, cataracts, and global developmental delay is described.

PMID- 7508319
TI  - Comparative effects of neurotensin and neuromedin N on growth of human pancreatic
      cancer, MIA PaCa-2.
AB  - Neurotensin (NT), an important regulatory hormone of the gut, stimulates growth
      of the human pancreatic cancer cell line MIA PaCa-2 in vitro. The purpose of our
      study was to compare the stimulatory effects of NT and neuromedin N (NMN), a
      structurally related hexapeptide, on the growth of MIA PaCa-2. In addition, the
      effects of NT on the growth of MIA PaCa-2 xenografts and normal GI tissues were
      assessed in athymic nude mice. MIA PaCa-2 cells, plated in serum-free media, were
      treated with either NT (10(-12)-10(-6) M) or NMN (10(-11)-10(-7) M) and cells
      were counted. For the in vivo study, MIA PaCa-2 cells were inoculated sc into 30
      athymic nude mice and then randomized to two groups to receive either NT (600
      micrograms kg-1, sc, tid) or vehicle. At sacrifice (day 35), the xenografted
      tumours, as well as normal host pancreas, jejunum and ileum were removed,
      weighed, and assayed for DNA, RNA and protein. Both NT and NMN stimulated the
      growth of MIA PaCa-2 cells in vitro with maximal (approximately 30%) increases
      occurring with dosages of 10(-9) M. In vivo, NT had a transient effect on
      xenografted MIA PaCa-2 tumour area with increases noted on days 21 and 25 of the
      study. Conversely, NT significantly stimulated the growth of jejunum and ileum,
      with a more pronounced effect noted in the jejunum. NT and NMN have similar
      growth-stimulatory effects on MIA PaCa-2 cells in vitro, which suggests an
      interaction through the same receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508320
TI  - Combined percutaneous transhepatic and endoscopic placement of biliary stents.
AB  - Combined percutaneous transhepatic cholangiography and endoscopic retrograde
      cholangiography can be used to stent biliary obstruction when attempts at
      endoscopic stenting have failed. Between January 1987 and August 1991 we
      performed 35 combined procedures in 31 patients with malignant obstruction. Post
      stenting serum bilirubin and serum alkaline phosphatase concentration fell after
      33 and 29 procedures, respectively. In six studies there was evidence of
      infection prior to stenting. In spite of the use of prophylactic antibiotics,
      septic complications developed after eight procedures (23%). Pseudomonas was the
      most commonly isolated pathogen (46%). Twenty-three patients were discharged, 30
      day mortality was 8 (23%) and median survival was 14 weeks (range 0-75 weeks).
      Seven patients required eight stent changes because of blockage (median patency
      time 18 weeks; range 7-75 weeks). Use of this technique allows relief of biliary
      obstruction. Potential infective and bleeding complications must be anticipated.

PMID- 7508321
TI  - Central vein occlusion study of photocoagulation. Manual of operations. Central
      Vein Occlusion Study Group.
AB  - This paper is the complete protocol (Manual of Operations) used in the Central
      Vein Occlusion Study (CVOS). The CVOS is a randomized clinical trial and natural
      history study of central retinal vein occlusion supported by the National Eye
      Institute. The administrative structure includes a Data and Safety Monitoring
      Board, 9 clinical centers, a coordinating center, and a photograph reading
      center. The Manual of Operations describes study design, organization, policies,
      and procedures. Procedures described in detail include measurement of visual
      acuity, fundus and iris photography, fluorescein angiography, and quality
      control.

PMID- 7508322
TI  - Central vein occlusion study of photocoagulation therapy. Baseline findings.
      Central Vein Occlusion Study Group.
AB  - OBJECTIVE: Description of the patients recruited into the Central Vein Occlusion
      Study (CVOS) and of the status of their eyes at time of study entry. This
      population is currently being followed for evaluation of photocoagulation
      treatment for eyes with central retinal vein occlusion (CVO) and natural history.
      DESIGN: Prospective multicenter cohort study incorporating 2 natural history
      groups and 2 randomized controlled clinical trials. SETTING: Eight ophthalmic
      practices in the USA and 1 in France, primarily associated with academic centers.
      PATIENTS: Seven hundred and twenty-five patients with CVO (728 eyes) divided into
      4 study groups on the basis of the perfusion status of the retina and presence of
      decreased vision associated with macular edema: perfused, nonperfused,
      indeterminate, and macular edema. INTERVENTIONS: Nonperfused group: random
      assignment to panretinal photocoagulation or watchful waiting. Macular edema
      group: random assignment to grid pattern photocoagulation or watchful waiting.
      Natural history groups: no intervention. MAIN OUTCOME MEASURES: Description of
      population and eyes based upon clinical examination and central assessment of
      fundus angiography, iris photographs, and stereo color fundus photographs. MAIN
      RESULTS: Mean age for the 725 patients is 65 years, with 43% of patients in the
      study age 70 or older. Despite the older age of this population, more than half
      (53%) of the patients are male. One hundred and eighty-one patients were
      randomized into the nonperfused group and 155 into the macular edema group.
      Follow-up in the CVOS will be completed in February 1994 when most patients are
      expected to have completed the planned 3 years. CONCLUSIONS: Recruitment has been
      successfully completed in this prospective study and the design and baseline
      results are presented.

PMID- 7508325
TI  - Inhibition by rapamycin of leukocyte migration and bronchial hyperreactivity
      induced by injection of Sephadex beads to guinea-pigs.
AB  - 1. The effect of rapamycin (0.001 to 5 mg kg-1) on the increased leukocyte counts
      in bronchoalveolar lavage (BAL) fluid and hyperreactivity of isolated bronchial
      strips to histamine and acetylcholine (ACh) was studied following the intravenous
      injection of Sephadex beads to guinea-pigs. 2. The intramuscular (i.m.) injection
      of rapamycin (0.012 to 5 mg kg-1) dose-dependently inhibited the increase in
      leukocyte counts in BAL fluid. Rapamycin (5 mg kg-1) reduced the numbers of
      eosinophils neutrophils, macrophages and lymphocytes in BAL fluid by 64, 55, 19
      and 50% respectively. In addition, rapamycin (0.012 to 5 mg kg-1) significantly
      inhibited the Sephadex-induced hyperreactivity of bronchial tissue to both
      histamine and ACh. 3. At a dose of 0.001 mg kg-1, rapamycin did not significantly
      reduce leukocyte infiltration or bronchial hyperreactivity. 4. Cyclosporin (5 mg
      kg-1) significantly reduced both lymphocyte and eosinophil numbers in BAL fluid
      of Sephadex-injected guinea-pigs whereas dexamethasone (1 mg kg-1) significantly
      reduced lymphocyte numbers. Neither drug affected the bronchial hyperreactivity
      to histamine and ACh. 5. It is concluded that the new immunosuppressive drug,
      rapamycin, is a potent inhibitor of leukocyte migration and bronchial
      hyperreactivity observed following the intravenous injection of Sephadex beads to
      guinea-pigs. Rapamycin also appears to be more effective than cyclosporin or
      dexamethasone in reducing leukocyte counts and bronchial hyperreactivity in this
      model. 6. Our results suggest that inflammatory mechanisms which are inhibited by
      rapamycin may be important in the induction of Sephadex-induced hyperreactivity.

PMID- 7508324
TI  - Cardiovascular effects of intrathecally administered bradykinin in the rat:
      characterization of receptors with antagonists.
AB  - 1. The effects of intrathecal (i.t.) pretreatment with selective B1 or B2 kinin
      receptor antagonists were studied on the cardiovascular response to i.t.
      injection of bradykinin (BK) in conscious freely moving rats. 2. BK (81 pmol)
      produced an increase in mean arterial pressure (MAP: 9-13 mmHg) and decrease in
      heart rate (HR: 20-30 beats min-1) that reached a maximum 2 min after injection.
      3. The BK-induced cardiovascular responses were dose-dependently and reversibly
      reduced by four antagonists with the following rank order of potency: Tyr, D
      Arg[Hyp3,D-Phe7,Leu8]-BK = D-Arg[Tyr3,D-Phe7,Leu8]-BK = D- Arg[Hyp3,D-Phe7,Leu8]
      BK > D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-BK (Hoe 140). These compounds failed to alter
      the cardiovascular response to i.t. injection of 8.1 nmol of substance P. 4.
      Other compounds acting on the B2 receptor, namely D-Arg[Hyp3,Gly6,Leu8]-BK, D
      Arg[Hyp3,D-Phe7]-BK, D-Arg[Hyp2,Thi5,8,D-Phe7]-BK and D-Arg[Hyp3,Gly6,D
      Phe7,Leu8]-BK or on the B1 receptor, [Leu8]-desArg9-BK, did not influence the
      cardiovascular responses to BK at doses devoid of intrinsic activity on MAP and
      HR. 5. None of the kinin receptor antagonists caused motor impairment,
      respiratory arrest or persisting cardiovascular changes. 6. These results confirm
      that the cardiovascular effects induced by i.t. BK are mediated by the activation
      of a B2 receptor in the rat spinal cord. However, the rank order of potency of
      antagonists does not conform to the classical B2 functional site characterized in
      peripheral tissues.

PMID- 7508323
TI  - The biology of nitrogen oxides in the airways.
AB  - Nitrogen oxides (NOx), regarded in the past primarily as toxic air pollutants,
      have recently been shown to be bioactive species formed endogenously in the human
      lung. The relationship between the toxicities and the bioactivities of NOx must
      be understood in the context of their chemical interactions in the pulmonary
      microenvironment. Nitric oxide synthase (NOS) is a newly identified enzyme system
      active in airway epithelial cells, macrophages, neutrophils, mast cells,
      autonomic neurons, smooth muscle cells, fibroblasts, and endothelial cells. The
      chemical products of NOS in the lung vary with disease states, and are involved
      in pulmonary neurotransmission, host defense, and airway and vascular smooth
      muscle relaxation. Further, certain patients with pulmonary hypertension, adult
      respiratory distress syndrome and asthma may experience physiologic improvement
      with NOx therapy, including inhalation of nitric oxide (NO.) gas. Both endogenous
      and exogenous NOx react readily with oxygen, superoxide, water, nucleotides,
      metalloproteins, thiols, amines, and lipids to form products with biochemical
      actions ranging from bronchodilation and bacteriostasis (S-nitrosothiols) to
      cytotoxicity and pulmonary capillary leak (peroxynitrite), as well as those with
      frank mutagenic potential (nitrosamines). Recent discoveries demonstrating the
      relevance of these species to the lung have provided new insights into the
      pathophysiology of pulmonary disease, and they have opened a new horizon of
      therapeutic possibilities for pulmonary medicine.

PMID- 7508326
TI  - Selective inhibition by dexamethasone of induction of NO synthase, but not of
      induction of L-arginine transport, in activated murine macrophage J774 cells.
AB  - 1. Effects of dexamethasone on induction of nitric oxide (NO) synthase and L
      arginine transport by lipopolysaccharide (LPS) were examined in a murine cultured
      macrophage cell line J774. Metabolism of L-arginine to L-citrulline and
      subsequent changes in intracellular amino acids pools were correlated with
      changes in nitrite production. 2. Despite a high intracellular concentration of
      arginine in activated J774 cells, LPS (1 microgram ml-1, 8 h) induced a 2.4 fold
      increase in arginine transport. Treatment of cells with cycloheximide (1
      microgram ml-1) inhibited the time-dependent (1-8 h) induction of NO synthase and
      arginine transport mediated by LPS. 3. Induction of NO synthase by LPS (1
      microgram ml-1, 24 h) alone was accompanied by a marked increase in arginine
      utilisation leading to decreased intracellular arginine levels and elevated
      intracellular and extracellular L-citrulline levels. These changes were further
      enhanced in the presence of interferon-gamma (IFN-gamma, 100 units ml-1, 24 h).
      4. Dexamethasone (1 microM) abolished the increases in both nitrite and
      citrulline production induced by LPS alone but only partially reversed the
      combined effects of LPS and IFN-gamma. In contrast, treatment of cells with
      dexamethasone (10 microM) had no effect on the LPS-mediated induction of arginine
      transport or the decrease in intracellular arginine concentration. 5. We conclude
      that induction of arginine transporter activity in LPS-stimulated J774 cells
      involves de novo synthesis of carrier proteins, which increases transport of
      exogenous arginine during enhanced NO production. Moreover, the intracellular
      signalling pathways mediating induction of arginine transport and of NO synthase
      by LPS in activated macrophages diverge, since only the latter is sensitive to
      dexamethasone.

PMID- 7508327
TI  - Ionotropic glutamate receptor types leading to adenosine-mediated inhibition of
      electrically evoked [3H]-noradrenaline release in rabbit brain cortex slices.
AB  - 1. Glutamate inhibits the electrically evoked release of noradrenaline in rabbit
      brain cortex slices; the inhibition is mediated by adenyl compounds, presumably
      adenosine. The aim of the present study was to identify the receptors involved in
      this indirect inhibitory effect of glutamate. Slices of the occipitoparietal
      cortex were preincubated with [3H]-noradrenaline and then superfused and
      stimulated by trains of 6 pulses, 100 Hz. 2. The ionotropic glutamate receptor
      agonists alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AM-PA; 10-100
      microM), kainate (10-100 microM) and N-methyl-D-aspartate (NMDA; 30-300 microM)
      but not the metabotropic glutamate receptor agonist, 1-amino-1,3
      cyclopentanedicarboxylate (ACPD; 10-100 microM) reduced the electrically evoked
      overflow of tritium. 3. The effects of AMPA, kainate and NMDA were attenuated or
      abolished by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX) as well as by adenosine A1-receptor antagonist, 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX) as well as by adenosine deaminase but
      not by the alpha 2-adrenoceptor antagonist yohimbine, the gamma-aminobutyric acid
      (GABA) receptor antagonists, bicuculline and 2-hydroxysaclofen and the NO
      synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). 4. The NMDA
      receptor antagonist, 2-amino-5-phosphonopentanoate (AP5) blocked the inhibitory
      effect of NMDA but not that of AMPA and kainate. The non-NMDA-receptor
      antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked the effect of
      AMPA but not of kainate and NMDA. 5. In addition to decreasing the electrically
      evoked overflow of tritium, AMPA, kainate and NMDA but not ACPD caused a steep
      but transient rise of basal tritium efflux. This immediate releasing effect was
      not significantly changed by DPCPX, adenosine deaminase, yohimbine, bicuculline,
      2-hydroxysaclofen and L-NAME (except that L-NAME enhanced the effect of kainate).
      AP5 and CNQX antagonized the immediate releasing effects in the same way that
      they antagonized the inhibition by AMPA, kainate and NMDA of the electrically
      evoked overflow of tritium.6. It is concluded that AMPA, kainate and NMDA, like
      glutamate, reduce the electrically evoked release of noradrenaline by releasing
      adenosine or an adenine nucleotide which is then degraded to adenosine.
      Activation of each of the three ionotropic glutamate receptors, AMPA, kainate and
      NMDA receptors, but not activation of metabotropic glutamate receptors can
      initiate this indirect inhibitory effect on the release of noradrenaline (as well
      as the known noradrenaline releasing effect).

PMID- 7508328
TI  - Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model:
      comparison with arachidonic acid-induced ear oedema.
AB  - 1. We have investigated the mechanism of capsaicin-induced mouse ear oedema
      compared with that of arachidonic acid (AA)-induced ear oedema, and evaluated the
      possible involvement of neuropeptides in the development of capsaicin-induced
      oedema. 2. Topical application of capsaicin (0.1-1.0 mg per ear) to the ear of
      mice produced immediate vasodilatation and erythema followed by the development
      of oedema which was maximal at 30 min after the treatment. This oedema was of
      shorter duration with less swelling than AA-induced oedema (2.0 mg per ear). 3.
      Capsaicin-induced ear oedema was unaffected when inhibitors of arachidonate
      metabolites including platelet activating factor (PAF) were administered before
      capsaicin (250 micrograms per ear) application, while these agents significantly
      prevented AA-induced oedema. Dexamethasone, histamine H1 and/or 5
      hydroxytryptamine (5-HT) antagonists, and substance P (SP) antagonists were
      effective in inhibiting both models. Furthermore, a Ca(2+)-channel blocker and
      the capsaicin inhibitor, ruthenium red, were effective inhibitors of capsaicin
      oedema but had no effect on AA-induced oedema. 4. Phosphoramidon (50 micrograms
      kg-1, i.v.), an endopeptidase inhibitor, markedly (P < 0.001) enhanced only
      capsaicin-induced ear oedema, but bestatin (0.5 mg kg-1, i.v.), an
      aminopeptidase, failed to enhance oedema formation. 5. Neuropeptides (1-100 pmol
      per site) such as rat calcitonin gene-related peptide (CGRP), SP, neurokinin A
      (NKA), and vasoactive intestinal peptide (VIP), which are released from capsaicin
      sensitive neurones, caused ear oedema by intradermal injection. Furthermore, a
      synergistic effect of CGRP (10 fmol per site) and SP (10 pmol per site) on oedema
      formation was observed. 6. The oedema induced by neuropeptides was significantly
      (P<0.05 or P<0.001) inhibited when cyproheptadine (20 mg kg-1, p.o.), a histamine
      H, and 5-HT antagonist, was administered before injection. In contrast,
      nifedipine (50 mg kg-1, p.o.), a Ca2+-channel blocker, and indomethacin(10 mg kg
      1, p.o., except for NKA), a cyclo-oxygenase inhibitor, had little effect on
      neuropeptide induced oedema.7. These results suggest that the mechanism of
      capsaicin-induced ear oedema is different from that of AA-induced oedema and
      suggest that the development of capsaicin-induced ear oedema is primarily
      mediated by neuropeptides. The neuropeptides released after activation of sensory
      nerves cause an increase of vascular permeability by interactions with
      endothelial cells and by histamine (and 5-HT)release from mast cells.

PMID- 7508329
TI  - Dopamine D2 receptor occupancy in vivo and response to the new antipsychotic
      risperidone.

PMID- 7508331
TI  - Alpha-blocking treatment with alfuzosin in symptomatic benign prostatic
      hyperplasia: comparative study with prazosin. The PRAZALF Group.
AB  - Alfuzosin, a selective alpha 1-adrenoceptor antagonist which is effective in the
      symptomatic treatment of benign prostatic hyperplasia (BPH), was compared with
      prazosin, another drug commonly used for the same purpose. After a 1-week placebo
      run-in period, 103 patients with day-time frequency > or = 7 or nocturia > or = 2
      and peak flow rate < 15 ml/s were randomised to receive either alfuzosin (2.5 mg
      tid) or prazosin (2 mg bid) for 3 weeks, with a gradual dose increase during the
      first week, in a double-blind, parallel group, multicentre study. Voiding
      symptoms, assessed on the basis of the Boyarsky scale and a micturition diary,
      were significantly improved in both groups, as were urinary flow rates. However,
      neither the clinical improvement nor the increase in flow rates differed
      significantly between the 2 groups. The peak flow rate increased similarly with
      alfuzosin (2.6 +/- 0.6 ml/s) and prazosin (2.9 +/- 0.7 ml/s); the mean flow rate
      and voided volume increase tended to be more marked with alfuzosin (30 and 22.2%
      respectively) than with prazosin (20.6 and 6.5%). Clinical safety was good in
      both groups. All 4 adverse events in the prazosin group but only 1 of the 4
      adverse events in the alfuzosin group were related to a decrease in blood
      pressure. It was concluded that alfuzosin was at least as effective as prazosin
      in the treatment of symptomatic patients with BPH and the incidence of adverse
      events related to their vasodilatory properties was lower with alfuzosin.

PMID- 7508332
TI  - Early removal of catheter following transurethral resection of the prostate.
AB  - This study was conducted on 83 patients who underwent an uncomplicated
      transurethral resection of the prostate for carcinoma or benign hyperplasia. In
      all cases the urethral catheter was removed within 24 h of surgery. Only 2
      patients failed to void because of clot retention. The total hospital stay was 3
      days in 67 patients. There were no significant complications due to early removal
      of the catheter.

PMID- 7508330
TI  - Is beta-human chorionic gonadotrophin production by transitional cell carcinoma
      of the bladder a marker of aggressive disease and resistance to radiotherapy?
AB  - The biopsies from 75 patients with transitional cell carcinoma of the bladder (25
      Ta-T1; 45 T2-T4, 5M) were studied immunohistochemically for the expression of
      beta-human chorionic gonadotrophin (beta-HCG). Only 5 Ta-T1 tumours contained a
      small number of beta-HCG positive cells but 24 invasive tumours and all patients
      with metastases showed increased numbers of positive cells. A significant
      correlation was found between beta-HCG immunoreactivity and tumour category. In
      30 patients with muscle-invasive disease (T2-T4,N0,M0) who were treated with
      radical radiotherapy a significant correlation was observed between response to
      treatment and beta-HCG expression; beta-HCG positive tumours did not respond to
      treatment. A difference in survival was found between patients with tumours
      negative for beta-HCG compared with patients with positive tumours, all treated
      with radical radiotherapy. The results indicate that beta-HCG expression
      increases with tumour invasiveness and the use of immunohistochemistry may prove
      a useful means of identifying radioresistant and aggressive forms of bladder
      cancer.

PMID- 7508333
TI  - Specific 16S ribosomal RNA targeted oligonucleotide probe against Clavibacter
      michiganensis subsp. sepedonicus.
AB  - In this article we report on the polymerase chain reaction amplification of a
      partial 16S rRNA gene from the plant pathogenic bacterium Clavibacter
      michiganensis subsp. sepedonicus. A partial sequence (about 400 base pairs) of
      the gene was determined that covered two variable regions important for
      oligonucleotide probe development. A specific 24mer oligonucleotide probe
      targeted against the V6 region of 16S rRNA was designed. Specificity of the probe
      was determined using dot blot hybridization. Under stringent conditions (60
      degrees C), the probe hybridized with all 16 Cl. michiganensis subsp. sepedonicus
      strains tested. Hybridization did not occur with 32 plant pathogenic and
      saprophytic bacteria used as controls under the same conditions. Under less
      stringent conditions (55 degrees C) the related Clavibacter michiganensis subsp.
      insidiosus, Clavibacter michiganensis subsp. nebraskensis, and Clavibacter
      michiganensis subsp. tesselarius also showed hybridization. At even lower
      stringency (40 degrees C), all Cl. michiganensis subspecies tested including
      Clavibacter michiganensis subsp. michiganensis showed hybridization signal,
      suggesting that under these conditions the probe may be used as a species
      specific probe for Cl. michiganensis.

PMID- 7508334
TI  - Prediction of adjustment from preschool to middle childhood.
AB  - This study identified predictor variables associated with outcome in middle
      childhood in a clinical preschool sample. These variables were examined in
      relation to functional level at outcome. At Time 1 the sample consisted of 129
      children admitted to a psychiatric preschool program; 82 of these children
      comprised the follow-up sample at Time 2. The results indicated that the
      variables significantly associated with each child's outcome were IQ, the
      presence of diagnosis at Time 1 and the length of time each child was in the
      treatment program. Different predictors were important for different outcomes and
      a given predictor variable was not equally salient across all levels of outcome.

PMID- 7508335
TI  - Gross and microscopic pathology of induced prostatic complex tumors arising in
      Lobund-Wistar rats.
AB  - The necessity for additional animal models for prostate cancer has recently been
      stressed. The Pollard model of chemically induced prostate cancer has received
      attention in this regard although the histiogenetic origin of these tumors has
      come under question. We independently studied this model for the development of
      tumors in the prostate region. The tumors, all of which were adenocarcinomas,
      first became grossly evident 5 months after induction and ultimately occurred in
      71% of the animals. Seventy-three % of the tumors involved only the seminal
      vesicle, 22% involved other portions of the prostatic complex as well as the
      seminal vesicle, and 5% were located in the coagulating gland (anterior
      prostate). Although the majority of tumors arose in or involved the seminal
      vesicle, this may still be a useful model for the study of human prostate cancer
      because the tumors are adenocarcinomas, occur in the large majority of animals,
      are hormonally induced, and have the propensity to metastasize.

PMID- 7508337
TI  - Demonstration and characterization of the angiogenic properties of cervical
      dysplasia.
AB  - Cervical dysplasia, or cervical intraepithelial neoplasia (CIN), is a
      premalignant precursor to cervical cancer. This study was designed to determine
      whether dysplastic lesions are angiogenic. Tissue sections from 23 surgical
      specimens were immunohistochemically stained for factor VIII antigen, a marker
      for endothelial cells. The results demonstrate that a region of
      neovascularization develops along the basement membrane subtending dysplastic
      epithelium when compared to adjacent normal epithelium. Comparison of microvessel
      counts underlying low grade lesions (condyloma and CIN I) with microvessel counts
      of CIN III lesions shows a statistically significant increase in the more
      advanced lesions. In a subset of the high grade lesions, large vascular
      structures are also noted in the upper layers of the epithelium, suggesting that
      a second stage of neovascularization consists of extension of stromal vascular
      papillae into the dysplastic lesions toward the surface of the epithelium. There
      is no statistical correlation between the amount of inflammation and the
      angiogenic ratio for each lesion, implying that angiogenesis is not secondary to
      the inflammatory response evoked by the lesion. The human papillomavirus type
      present in four CIN III lesions was determined by in situ hybridization; the
      amount of angiogenesis appears to be independent of the human papillomavirus
      type.

PMID- 7508336
TI  - Inverse correlation between expression of inducible nitric oxide synthase
      activity and production of metastasis in K-1735 murine melanoma cells.
AB  - The purpose of these studies was to determine whether the induction of NO
      synthase activity in murine K-1735 melanoma cells correlated with their
      metastatic potential. Nonmetastatic, metastatic, and somatic cell hybrids
      (produced by fusion of nonmetastatic and metastatic cells) were injected i.v.
      into syngeneic C3H/HeN mice. Metastatic cells survived to produce experimental
      lung metastases, whereas nonmetastatic cells did not. The various clones and
      somatic cell hybrids were incubated in vitro with combinations of tumor necrosis
      factor, interleukin 1, gamma-interferon, and lipopolysaccharide. Nonmetastatic
      cells exhibited high levels of inducible NO synthase activity and NO, whereas
      metastatic cells did not. Both the cytotoxic effects of the cytokines and NO
      production were inhibited by the addition of NG-monomethyl-L-arginine, a specific
      inhibitor of NO synthase. These data demonstrate an inverse correlation between
      production of endogenous NO and the ability of K-1735 cells to survive in
      syngeneic mice to produce lung metastases.

PMID- 7508338
TI  - Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of
      human prostatic cells.
AB  - Cultures of adult human prostatic epithelial and fibroblastic cells were
      established from normal, benign hyperplastic, and malignant tissues. Vitamin D
      receptors were detected by ligand binding of [3H]1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] in cytosolic extracts prepared from all types of cell cultures as
      well as from fresh prostatic tissues. Vitamin D receptor transcripts were
      demonstrated by Northern blot analysis. 1,25-(OH)2D3 inhibited the growth of
      epithelial cells with half-maximal inhibition at approximately 1 nM. The growth
      of fibroblasts was also inhibited by 1,25(OH)2D3 but to a lesser extent. This is
      consistent with the apparently lower level of vitamin D receptors in fibroblasts
      compared to epithelial cells determined by ligand binding and Northern analysis
      of RNA transcripts. The growth inhibition of epithelial cells by 1,25(OH)2D3 was
      irreversible even after a short 2-h exposure, but morphology and keratin
      expression were not appreciably altered by long-term exposure to the hormone. A
      physiological role for 1,25(OH)2D3 in the prostate is postulated, and the
      inhibitory effect of 1,25(OH)2D3 on cancer-derived prostate cells may provide a
      basis for new preventive or therapeutic strategies.

PMID- 7508340
TI  - [Hepatitis C virus antibodies in persons on dialysis].
AB  - Using the ELISA method (generation II), the authors made a single examination of
      172 dialyzed patients for the presence of antibodies against the virus of
      hepatitis C (VHC). Antibodies were detected in 82 subjects, i. e. 47.7%. The
      prevalence of antibodies in the examined subjects increased with the number of
      dialyses, no relationship was found with the number of transfusions. Of 104
      subjects where during inclusion into the dialyzation transplantation programme a
      rise of ALT occurred 69, i. e. 66.3%, had antibodies. Antibodies were detected in
      17 of 44 subjects (38.6%) to whom so far blood was not administered. A decisive
      place in the prevention of VHC transmission in dialyzed subjects is held by non
      specific preventive measures, transfusions are most probably not the decisive
      vehicle.

PMID- 7508339
TI  - Epitope masking of rat esophageal carcinoma tumor-associated antigen by certain
      coexisting glycolipid and phospholipid molecules: a potential mechanism for tumor
      cell escape from the host immune responses.
AB  - A monoclonal antibody (mAb-5G) produced against a tumorigenic rat esophageal cell
      line, B2T, was shown to react specifically with a unique glycolipid antigen
      expressed on the cell surface of tumorigenic and certain non-tumorigenic,
      immortalized rat esophageal cell lines [Cancer Immunol Immunother 36: 94 (1993)].
      In enzyme-linked immunosorbent assay experiments, mAb-5G reacted with crude lipid
      extracts prepared from B2T cells cultured in vitro, but showed very little
      reactivity with crude lipid extracts prepared from the same cell line passaged
      once in vivo, unless the antigen was separated from other lipid components by
      column or thin-layer chromatography (TLC). When a secondary tissue-culture cell
      line was established from the above B2T tumor tissues and serially subcultured in
      vitro, the percentage of positively stained cells was increased significantly in
      immunofluorescence assay. It was also demonstrated that the amount of extractable
      antigen was increased as the cells were subcultured in vitro up to passage 15,
      and stabilized thereafter. These results indicate the presence of certain lipid
      components in crude lipid extracts from B2T cells grown in vivo that are capable
      of interfering with antigen-antibody binding. On TLC plates, these interfering
      lipids were identified as phosphatidylcholine, phosphatidylserine, sphingomyelin
      and gangliosides. The interfering lipids did not bind the antibody, rather they
      appeared to interfere with antigen accessibility. These lipid substances may
      modify tumor cell surface antigen(s), thus protecting the tumor cells from host
      immune destruction.

PMID- 7508341
TI  - Urinary excretion of modified nucleosides as biological marker of RNA turnover in
      patients with cancer and AIDS.
AB  - Using boronate gel affinity chromatography and reversed-phase high-performance
      liquid chromatography (RP-HPLC), a method for the simultaneous determination of
      12 urinary modified nucleosides has been developed. The RP-HPLC fractions were
      identified by gas chromatography/mass spectrometry analysis. The HPLC
      quantitation of urinary nucleoside levels before and after surgery of cancer
      patients suggested that urinary 5'-deoxy-5'-methylthioadenosine and N-[(9-beta-D
      ribofuranosyl-9H-purine-6-yl) carbamoyl]-L-threonine (t6A) levels were helpful in
      monitoring therapeutic effects in cancer patients. From the fact that molar
      ratios of urinary N2,N2-dimethylguanosine (m2 2G)pseudouridine (psi) and t6A/psi
      in cancer patients were lower than those of normal or post-surgical cancer
      patients, the increase of rRNA content in cancer tissues growing rapidly was
      estimated using the stoichiometric relationship between the ratio of the number
      of residues of their modified nucleoside in RNAs and the proportion of rRNA to
      total RNAs in average tissues of whole body. Furthermore, from the estimation of
      RNA turnover using urinary nucleoside levels, it was found that the half-lives of
      rRNA rather than tRNA of patients with cancer and those of both RNAs in the case
      of acquired immunodeficiency syndrome (AIDS) were extremely short compared with
      those of the normal. Thus, we discovered that the selected urinary modified
      nucleosides were very useful as a biological marker of whole-body RNA turnover in
      patients with cancer and AIDS.

PMID- 7508342
TI  - Serum sialic acid and acute phase proteins in type 1 and type 2 diabetes
      mellitus.
AB  - Serum sialic acid is a risk factor for cardiovascular disease in the general
      population. Serum total sialic acid concentrations were therefore measured in 20
      type 1 diabetic patients and in 20 age- and sex-matched non-diabetic subjects.
      Serum sialic acid were not significantly different in the type 1 diabetic
      patients and the normal subjects (2.00 +/- 0.37 vs. 1.98 +/- 0.67 mmol/l), but
      was significantly correlated with serum total cholesterol (r = 0.55, P < 0.02)
      and serum triglyceride concentration (r = 0.63, P < 0.01) in the type 1 diabetic
      patients. There was no relationship of sialic acid levels to age, duration of
      diabetes, smoking, body mass index, systolic or diastolic blood pressure, plasma
      glucose, serum fructosamine, or daily insulin dosage. Six of the type 1 diabetic
      patients with retinopathy had higher total serum sialic acid concentrations than
      those patients without retinopathy (2.38 +/- 0.33 vs. 1.85 +/- 0.26 mmol/l, P <
      0.01). A further study of 16 type 1 and 16 type 2 diabetic patients matched for
      serum fructosamine and blood glucose concentrations and without tissue
      complications showed that the serum total sialic acid concentration was
      significantly higher in the type 2 diabetic patients compared with the type 1
      patients (2.32 +/- 0.41 vs. 1.84 +/- 0.24 mmol/l, P < 0.001). Although the serum
      concentrations of the non-sialylated acute phase protein, C-reactive protein, was
      higher in type 2 than type 1 diabetes, sialylated acute phase protein levels did
      not explain differences in serum total sialic acid in diabetes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7508343
TI  - Development and application of an enzyme immunoassay for tenascin.
AB  - A sandwich enzyme immunoassay system for detecting tenascin in human serum was
      established using purified antibodies to tenascin. The assay system comprises
      polystyrene balls with immobilized polyclonal antibody F(ab')2 fragments and
      monoclonal antibody F(ab')2 fragments labeled with beta-D-galactosidase from
      Escherichia coli. The assay system has a minimum detectable sensitivity of 10
      ng/ml of tenascin in human serum, with an assay range of 3 micrograms/ml. The
      assay system was found not to cross-react with laminin, vitronectin, human
      epidermal growth factor, fibrinogen, or fibronectin. Coefficients of variation
      within-run and between-run for the assay of human serum tenascin were less than
      10%. Serum samples from healthy adults (n = 86) contained about 800 ng/ml and
      serum tenascin concentrations of patients with carcinoma (n = 47) were increased.
      These results suggest that tenascin in serum might be a marker substance for
      carcinoma.

PMID- 7508344
TI  - Cytoplasmic islet cell antibodies (ICA): towards a molecular understanding of the
      autoantigens.

PMID- 7508345
TI  - Common variable immunodeficiency: does life begin at 40?

PMID- 7508347
TI  - Antibody reactivity to an Epstein-Barr virus BERF4-encoded epitope occurring also
      in Asp-57 region of HLA-DQ8 beta chain. Childhood Diabetes in Finland Study
      Group.
AB  - A five amino acids-long sequence (GPPAA) in the region of the 57th amino acid of
      HLA-DQ8 beta chain, which seems to be important in defining the risk for type 1
      diabetes, occurs also in the BERF4-encoded EBNA3C protein of Epstein-Barr virus
      (EBV) in six successive repeats. The antigenicity of this region was analysed
      using synthetic peptides containing different modifications of the GPPAA
      sequence. Two of the seven individuals who had acute EBV infection produced
      antibodies against an EBV-derived peptide (GPPAAGPPAAGPPAA) paralleling the EBNA2
      antibodies. These two cases also contracted type 1 diabetes immediately after the
      infection. High antibody levels against this peptide were found in a total of 12%
      of EBV+ individuals, and in most cases antibodies remained at high levels for
      several years. Human sera as well as affinity-purified antibodies specific for
      the GPPAAGPPAAGPPAA peptide reacted also with shorter peptide analogues
      (GPPAAGPPAA and GPPAA), as well as with peptides containing the surrounding
      motifs from DQ8 beta chains. However, none of these antibodies bound to denatured
      DQ8 beta chains in immunoblotting. The charge of the 57th amino acid modulated
      the antigenicity of this epitope, as peptides from Asp-57-negative DQ molecules
      were reactive, while peptides from Asp-57-positive DQ molecules were not. The
      responsiveness was seen in both HLA-DQ8-positive and -negative subjects as well
      as in type 1 diabetic individuals. The results suggest that some individuals who
      carry the GPPAA sequence in their HLA-DQ molecule recognize this epitope in EBV.
      This phenomenon may have potential importance in EBV-induced immune
      abnormalities, although cross-reactivity against DQ molecules could not be
      demonstrated in the present study.

PMID- 7508348
TI  - Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) expression and function on cultured human glomerular epithelial cells.
AB  - Glomerular epithelial cells are involved in extracapillary inflammation
      (crescents) but the mechanisms of this extracapillary accumulation of
      macrophages, epithelial cells and occasional lymphocytes are unknown. Human
      glomerular parietal epithelial cells express ICAM-1 and VCAM-1 on
      immunohistological stains of renal biopsies. We studied the expression of these
      cell adhesion molecules on cultured human glomerular epithelial cells (HGEC),
      their regulation by pro-inflammatory cytokines, and their role in mediating the
      adhesion of concanavalin A (Con A)-activated peripheral blood mononuclear cells.
      Human glomerular epithelial cells in culture constitutively express ICAM-1 and
      VCAM-1. The expression of ICAM-1 was not significantly altered by tumour necrosis
      factor-alpha (TNF-alpha) (P = 0.32), IL-1 beta (P = 0.24), interferon-gamma (IFN
      gamma) (P = 0.66) or IL-4 (P = 0.85). VCAM-1 expression was increased by all four
      cytokines, but only significantly so by IL-4 (P = 0.0001). Con A-stimulated,
      monocyte-depleted peripheral blood lymphocytes bound to human glomerular
      epithelial cells, median 28.9% (range 14.5-37.9%). This adherence was
      significantly inhibited by anti-ICAM-1 (P = 0.03) and anti-LFA-1 (P = 0.02), but
      not by anti-VCAM-1 (P = 0.13) or by antibody to von Willebrand factor (P = NS).
      The interaction between ICAM-1 on HGEC and LFA-1 on mononuclear cells may be
      important in the pathogenesis of extracapillary inflammation in
      glomerulonephritis.

PMID- 7508346
TI  - Surface molecules involved in the adherence of recombinant interferon-gamma (rIFN
      gamma)-stimulated human monocytes to vascular endothelial cells.
AB  - During an inflammatory reaction, an increased number of circulating monocytes
      adhere to the endothelial cells (EC) of the vessel wall. This process is mediated
      by molecules located on the surface of monocytes and EC. Locally released
      inflammatory mediators can modulate monocyte-EC interaction. In an earlier study
      we reported that stimulation of monolayers of cultured venous EC with rIFN-gamma
      enhanced their adhesiveness for monocytes. The aim of the present study was to
      investigate the effect of rIFN-gamma on peripheral blood monocytes with regard to
      the expression of surface molecules and the binding to non-stimulated or cytokine
      stimulated EC. Flow cytometric analysis demonstrated that monocytes stimulated
      with 500 U/ml rIFN-gamma for 24 h showed increased expression of CR3
      (CD11b/CD18), p150,95 (CD11c/CD18) and Fc gamma RI (CD64); the expression of LFA
      1 (CD11a/CD18), L-selectin, CD14 and VLA-4 (CD49d/CD29) did not change or was
      slightly reduced. Upon stimulation with rIFN-gamma monocytes showed an enhanced
      binding to both non-stimulated or rIFN-gamma-stimulated EC. This was even more
      pronounced when EC had been stimulated with rIL-1 alpha for 24 h. The increased
      binding of rIFN-gamma-stimulated monocytes to rIL-1 alpha-stimulated EC was
      further analysed. Studies with MoAbs against adhesion molecules on monocytes
      revealed that the binding of rIFN-gamma-stimulated monocytes, but not that of non
      stimulated monocytes, to rIL-1 alpha-stimulated EC was inhibited by about 30-60%
      with MoAbs against CD11a, CD11b, CD18, L-selectin or CD14. MoAbs against CD11c or
      CD49d had little or no effect. From these results, we conclude that exposure of
      monocytes to rIFN-gamma enhances their adhesiveness to cytokine-stimulated EC by
      a mechanism which involves CD11a/CD18, CD11b/CD18, CD14 and L-selectin on
      monocytes.

PMID- 7508349
TI  - Functional heterogeneity of mast cells isolated from different microenvironments
      within nasal polyp tissue.
AB  - Nasal polyposis is a chronic inflammatory condition of the upper airways
      characterized by infiltration of activated inflammatory cells, including mast
      cells, both in the epithelium and in the stroma. The aim of this work was to
      study human mast cells derived from two different anatomical sites within the
      same nasal polyp tissue. To this end, we isolated two distinct mast cell
      populations, one from the epithelial and the other from the stromal layers of
      individual human nasal polyp tissues. We examined the mediator content of the two
      mast cell populations and found that stromal mast cells had a significantly
      higher content of tryptase compared with the epithelial mast cells from the same
      tissue. In addition, mast cells from the stromal compartment, but not those from
      the epithelium, released a significant amount of histamine after anti-IgE
      stimulation. By contrast, both populations released over 50% of the total
      histamine after non-specific stimuli (A23187 10(-6) M). The content of mediators
      and the response to immunological activation were not significantly altered in
      patients receiving topical steroid therapy. It remains to be determined if the
      observed differences are the result of an intrinsic characteristic of the mast
      cell populations localized to separate tissue compartments, or reflect a
      different in vivo exposure to stimuli such as antigens, or different surrounding
      structural or infiltrating cells. In conclusion, these data provide evidence of
      functional heterogeneity and differences in mediator content between mast cell
      subpopulations from a single human tissue. The failure of release of epithelial
      mast cell mediators from an immunologic stimulus may have implications concerning
      acute effects of antigen exposure in nasal polyposis.

PMID- 7508350
TI  - C6 haplotypes: associations of a Dde I site polymorphism to complement deficiency
      genes and the Msp I restriction fragment length polymorphism (RFLP)
AB  - Complement C6 has a common charge polymorphism designated A and B with gene
      frequencies of 0.65 and 0.35. The probable molecular basis for this is a Glu
      (C6A) for Ala (C6B) substitution at amino acid position 98, and is detected by
      digestion with the restriction enzyme Dde I of a polymerase chain reaction (PCR)
      amplified fragment of genomic DNA. C6A was found to be Dde I-positive and C6B
      corresponds to Dde I-negative. We have applied our Dde I A/B polymorphism
      genotyping method to the investigation of C6-deficient individuals with complete
      (C6Q0) and sub-total deficiency (C6SD) protein phenotypes, including members of
      four families. We have also investigated the RFLP detected by digestion of
      genomic DNA with the enzyme Msp I, which is due to a polymorphic site located in
      the 5' section of the gene, the variable sequence of which has yet to be
      determined. Sixteen out of seventeen unrelated C6Q0 subjects were found to be
      genotypically Dde I B/Msp I-negative; the remaining subject was heterozygous at
      both the loci under investigation. The C6SD phenotype was found to be associated
      with the Dde I A/Msp I-positive genotype in two families with combined C6/C7
      subtotal deficiency and two with C6SD. It can be concluded that the two forms of
      C6 deficiency, C6Q0 and C6SD, arose independently on two different C6 allelic
      backgrounds. These associations have allowed the genotyping of the rare families
      that contain both types of deficiency. We have also defined a number of normal C6
      Dde I/Msp I haplotypes in Caucasians and Cape Coloured populations.

PMID- 7508354
TI  - Radiopharmaceutical approved for relief of pain caused by bone metastases.

PMID- 7508353
TI  - Effects of bradykinin on [3H]-norepinephrine release in rat hypothalamus.
AB  - 1. We examined the regulatory actions of bradykinin on norepinephrine release in
      the hypothalamus of rats. 2. Bradykinin increased the stimulation-evoked [3H]
      norepinephrine release from hypothalamic slices of Sprague-Dawley rats in a dose
      dependent manner (1 Hz: S2/S1 ratio, mean +/- s.e.m., control 0.868 +/- 0.016, n
      = 6; bradykinin 1 x 10(-6) mol/L 1.039 +/- 0.018, n = 6, P < 0.05; bradykinin 3.3
      x 10(-6) mol/L 1.130 +/- 0.064, n = 6, P < 0.05). The basal release of [3H]
      norepinephrine was not affected by the peptide. 3. Bay K 8644, a dihydropyridine
      sensitive calcium channel agonist, significantly potentiated the facilitatory
      effect of bradykinin on norepinephrine release, although Bay K 8644 by itself had
      no significant effect. By contrast, nicardipine, a dihydropyridine-sensitive
      calcium channel blocker, reversed the increase in norepinephrine release induced
      by bradykinin and Bay K 8644. 4. These results indicate that bradykinin may
      increase norepinephrine release in rat hypothalamus, partially mediated by
      interactions with dihydropyridine-sensitive calcium channels.

PMID- 7508352
TI  - Perfusion pressure and transmural flow distribution in the left ventricles of
      isolated rat hearts.
AB  - 1. The influence of perfusion pressure on flow distribution in the left
      ventricular wall was investigated with a newly developed microsphere method in
      Langendorff preparations of the rat heart. 2. Microspheres with a diameter of 10
      microns stained with the fluorescent dye yellow-green were infused into the
      perfusion medium. The hearts were then relaxed with a calcium-chelator, fixed
      with formaldehyde and cut transversally with a freezing microtome. Photographs
      were taken of the 52 microns slices with a fluorescence photomacroscope. The
      ventricular wall was subdivided into four zones, evaluated planimetrically and
      the beads were counted for calculation of microsphere density. 3. Perfusion of
      groups of hearts, paced at 5 Hz, with Tyrode's solution at pressures of 30, 50,
      80 or 120 cmH2O for 30 min revealed an increase of left ventricular pressure
      amplitude, coronary flow, myocardial oxygen consumption and flow redistribution
      towards the endocardium of the left ventricular wall with increasing perfusion
      pressure. 4. The quotient of the sphere densities in the inner endocardium over
      that in the outer epicardium, however, was already maximal at a pressure of 80
      cmH2O and amounted to 1.59 +/- 0.15. This quotient was only 0.52 +/- 0.11 at a
      perfusion pressure of 30 cmH2O, thus indicating massive change in flow
      distribution upon hypoperfusion. 5. These results indicate that transmural left
      ventricular flow redistribution in response to hypoperfusion in the isolated rat
      heart is similar to that in hearts of much larger species.

PMID- 7508351
TI  - Inhibitory effect of octopamine on the release of endogenous acetylcholine from
      isolated myenteric synaptosomes of guinea-pig.
AB  - 1. The effect of octopamine on the release of endogenous acetylcholine (ACh) from
      isolated ileal synaptosomal preparations of guinea-pigs was examined using high
      pressure liquid chromatography with electrochemical detection. Release of ACh was
      induced by substance P or by depolarization with high potassium (50 mmol/L) in
      medium containing atropine, propranolol and naloxone. 2. Octopamine produced a
      dose-dependent inhibition of substance P-induced ACh release. A similar
      inhibitory action of octopamine was found in the samples depolarized by high
      potassium as a reference. 3. The action of octopamine was not reversed by the
      dopamine receptor antagonists either for the DA-2 subtype, domperidone, or for
      the DA-1 subtype, SCH23390, or by haloperidol. However, idazoxan and yohimbine
      antagonized this octopamine-induced inhibition at concentrations sufficient to
      abolish the action of clonidine. 4. Failure of guanethidine or nomifensine to
      inhibit octopamine ruled out mediation by noradrenergic neurotransmitters. 5.
      Octopamine decreased the influx of [45Ca] stimulated by substance P into
      synaptosomal preparations and this was reversed by idazoxan or yohimbine at
      concentrations sufficient to block the action of clonidine. 6. Pertussis toxin
      abolished the inhibitory action of octopamine at a dose high enough to block the
      action of clonidine. 7. These results indicate that octopamine suppresses the
      influx of calcium ions into cholinergic nerve terminals of ileal synaptosomes of
      guinea-pigs via an activation of alpha 2-adrenoceptors coupled with a pertussis
      toxin-sensitive GTP-binding protein which results in a decrease of ACh release.

PMID- 7508355
TI  - p-Chlorophenylalanine damages pancreatic acinar cell of the chicken.
AB  - 1. Birds were injected intraperitoneally with DL-p-chlorophenylalanine (p-CP),
      which is an inhibitor of phenylalanine hydroxylase, or saline one day before the
      experiment. The weight and cell size of pancreas increased by the p-CP treatment.
      2. The application of acetylcholine (5.50 x 10(-9) to 5.50 x 10(-5) M) caused a
      dose dependent increase in amylase release from the superfused segment of
      pancreas, although the response significantly decreased in the pancreatic segment
      treated with p-CP, compared with the control.

PMID- 7508356
TI  - Comparison of organophosphorous acid anhydrolases from different species using
      monoclonal antibodies.
AB  - 1. Monoclonal antibodies were raised against squid hepatopancreas
      organophosphorous acid (OPA) anhydrolase (EC 3.1.8.2) and were used to study
      structural similarities with OPA anhydrolases isolated from different sources. 2.
      Common epitopes were identified in OPA anhydrolases with diverse origins, and
      with different substrate specificities. 3. Epitopes unique to the squid
      hepatopancreas OPA anhydrolase were identified; optic ganglion and hepatopancreas
      contain different enzymes which can be distinguished by their epitopes.

PMID- 7508357
TI  - Effect of feed restriction on serum somatotropin, insulin-like growth factor-I
      (IGF-I) and IGF binding proteins in cyclic heifers actively immunized against
      growth hormone releasing factor.
AB  - Feed restriction often increases serum somatotropin (ST) and decreases insulin
      like growth factor-I (IGF-I) in ruminants; however, the mechanisms responsible
      for this change in ST and IGF-I are not well defined. We investigated the effects
      of feed restriction on serum ST, IGF-I, IGF binding proteins (IGFBP), insulin and
      nonesterified fatty acids (NEFA) in cyclic Angus and Charolais heifers (n = 15)
      previously immunized against growth hormone releasing factor (GRFi) or human
      serum albumin (HSAi). Cows were fed a concentrate diet ad libitum (AL) or were
      restricted to 2 kg cotton seed hulls (R) for 4 d. Each heifer received each
      dietary treatment in a single reversal design. As anticipated, GRFi decreased ST,
      IGF-I and insulin (P < .05). In addition, GRFi decreased serum IGFBP-3 (P < .01),
      but increased IGFBP-2 (P < .01). Feed restriction resulted in an increase in
      serum ST in HSAi, but not in GRFi heifers. Regardless of immunization treatment,
      feed restriction decreased serum IGF-I and insulin, and increased NEFA (P < .01).
      In conclusion, the increase in serum ST levels observed during feed restriction
      was blocked by active immunization against GRF. However, feed restriction
      resulted in decreased serum IGF-I in GRFi heifers in spite of initial low levels
      of IGF-I (due to GRFi). Although GRFi decreased levels of IGFBP-3 and increased
      levels of IGFBP-2, feed restriction for 4 d did not alter serum IGFBP.

PMID- 7508358
TI  - Effects of the 21-aminosteroid, U74389F, on bleomycin-induced pulmonary fibrosis
      in rats.
AB  - OBJECTIVE: To determine if a new class of agents, the 21-aminosteroids, which are
      reportedly potent inhibitors of iron-dependent lipid peroxidation, could protect
      rats from bleomycin-induced pulmonary fibrosis. SUBJECTS: Fifty-five adult male
      Sprague-Dawley rats. DESIGN: Prospective, randomized, blinded, controlled trial.
      INTERVENTIONS: The rats were subjected to intratracheal bleomycin (or saline
      vehicle), and were then treated with the 21-aminosteroid, U74389F (20 mg/kg/day),
      or vehicle, for the next 7 days. MEASUREMENTS AND MAIN RESULTS: At 21 days after
      bleomycin administration, pulmonary fibrosis was assessed histologically as
      percent of lung fields with evidence of fibrosis. Pulmonary fibrosis was assessed
      biochemically by measuring pulmonary elastin and hydroxyproline content. To
      determine if a protective effect of U74389F was linked to the 21-aminosteroid's
      ability to suppress lipid peroxidation, two products of lipid peroxidation were
      assayed in the lungs at 7 and 14 days after bleomycin exposure. By histologic
      assessment, the 21-aminosteroid-treated, bleomycin-exposed animals were found to
      have significantly decreased the extent of pulmonary fibrosis when compared with
      the bleomycin control group (mean 48.6 +/- 20.0 [SD] % [n = 9] vs. 68.4 +/- 19.6%
      [n = 11]; p < .05). In addition, lung elastin was decreased by approximately 75%
      (p < .05) and hydroxyproline was decreased by approximately 50% (NS) in the 21
      aminosteroid-treated group when compared with the bleomycin control group. At 7
      and 14 days after bleomycin exposure, all bleomycin-exposed animals had evidence
      of increased lipid peroxidation (conjugated dienes and thiobarbituric acid
      reactive substances), but the 21-aminosteroid-treated, bleomycin-exposed animals
      had significantly decreased evidence of lipid peroxidation when compared with
      bleomycin controls. CONCLUSIONS: The 21-aminosteroid can substantially protect
      animals from bleomycin-induced pulmonary fibrosis and may prove useful in other
      lung diseases where iron-dependent, free-radical reactions and/or lipid
      peroxidation are presumed mechanisms of toxicity.

PMID- 7508359
TI  - Cornea-specific expression of K12 keratin during mouse development.
AB  - The full-length cDNA of mouse K12 keratin was characterized by sequencing
      overlapping cDNA clones isolated from a mouse cornea cDNA library. Using Northern
      blot hybridization, the radio-labeled cDNA hybridized to a 1.9 kb mRNA from adult
      cornea, but not from other mouse tissues including snout, esophagus, tongue, and
      skin. During mouse development, corneas do not express K12 mRNA until 4 days
      postnatal when the epithelium begins to stratify as judged by Northern blot and
      in situ hybridization. In situ hybridization with 3H-labeled cDNA probe and
      immunohistochemical studies with antibodies against a synthetic oligo-peptide
      deduced from rabbit K12 cDNA demonstrate that this mouse K12 keratin is expressed
      in all cell layers of adult corneal epithelium, and the suprabasal layers, but
      not the basal layer of the limbal epithelium. Epidermal growth factor (EGF) has
      been shown to promote epithelium stratification of cultured chicken and human
      corneas in vitro. To examine whether EGF can promote K12 expression, EGF was
      administered to neonatal mice. The results indicate that EGF retards K12
      expression by corneal epithelial cells, even though it promotes corneal
      epithelial stratification during mouse development. Taken together, our results
      demonstrate that the expression of K12 keratin is cornea-specific,
      differentiation-dependent, and developmentally regulated.

PMID- 7508360
TI  - Increasing cell density down-regulates the expression of acidic FGF by human RPE
      cells in vitro.
AB  - Previous studies have reported the expression of acidic fibroblast growth factor
      (aFGF) by rat, bovine, and human retinal pigment epithelium (RPE) in vivo. To
      critically examine the expression of aFGF by RPE cells, we studied the density
      dependence of steady-state levels of mRNA and protein expression in vitro.
      Northern blot analysis demonstrated 5 transcripts ranging from 4.5 kB to 1 kB.
      Steady-state levels of all the transcripts decreased as a function of culture
      density. A polyclonal antibody was raised against recombinant human aFGF and
      affinity purified on aFGF coupled to AffiGel-10. The resulting antibody
      crossreacted with bFGF but not FGF-5, but this crossreactivity could be
      eliminated by absorption of the antibody on bFGF coupled to AffiGel-10. The final
      antibody preparation recognized only a single band at approximately 18.5 kD in
      lysates of RPE. Immunohistochemical staining with this antibody preparation
      demonstrated a marked dependence on cell density after 3 days in culture. Low
      culture density yielded cells staining moderately for aFGF, while confluent cells
      exhibited little or no staining. The reduction of aFGF from RPE cells in culture
      in a density-dependent fashion could also be demonstrated by Western blot
      analysis.

PMID- 7508361
TI  - Expression of CD14 correlates with lung function impairment in pulmonary
      sarcoidosis.
AB  - CD14 expression on alveolar macrophages (AM) was studied in patients with
      sarcoidosis using immunocytochemistry and cytometric analysis. Compared with
      healthy control donors, patients had elevated percentages of CD14-positive AM (22
      percent vs 34 percent), and the antigen density was threefold higher (92 vs 297
      channels). Furthermore, soluble serum CD14 (ssCD14) was significantly elevated in
      patients with sarcoidosis with an average of 5.3 +/- 1.6 mg/L vs 3.2 +/- 0.7 mg/L
      in healthy control subjects. Follow-up of one patient, whose lung function test
      results improved during therapy with corticosteroids, revealed a concomitant
      decrease of CD14 staining on AM and of ssCD14. Statistical analysis revealed a
      negative correlation between CD14 expression on AM and PO2 at rest (p = 0.0005),
      and after labor (p = 0.02). Levels of ssCD14 gave a positive correlation to
      reduction of Dco (p = 0.006) and VC (p = 0.05). These data suggest that CD14
      expression is related to severity of disease and that it may be useful for
      monitoring in sarcoidosis.

PMID- 7508362
TI  - Hepatotoxicity associated with acetaminophen usage in patients receiving multiple
      drug therapy for tuberculosis.
AB  - We report three patients who experienced hepatotoxic reactions in association
      with acetaminophen ingestion while undergoing treatment for active tuberculosis
      with isoniazid, rifampin, and other agents. All were young adult women. One
      patient intentionally took a large amount of acetaminophen and had typical signs
      and symptoms of acetaminophen overdosage; another took acetaminophen in
      combination form for a minor upper respiratory illness. She experienced no
      symptoms. The remaining patient took acetaminophen to ameliorate the symptoms of
      fever and malaise that were subsequently attributed to tuberculosis. She had the
      rapid onset of signs and symptoms of isoniazid hepatotoxicity. The patterns of
      liver function abnormalities were similar: each patient experienced pronounced
      serum elevations of hepatocellular enzymes with at most only modest rises in
      those of bilirubin. All antituberculous drugs were withheld until symptoms
      resolved and laboratory values became normal; then treatment for tuberculosis was
      resumed without isoniazid and was successfully completed in all three patients.
      These cases plus similar reports in the literature suggest that isoniazid or
      rifampin, or both, may potentiate the hepatotoxicity of acetaminophen, perhaps by
      induction of cytochrome P450 isozymes that oxidize acetaminophen to its toxic
      metabolites.

PMID- 7508363
TI  - The development of chromosome-specific composite DNA probes for the mouse and
      their application to chromosome painting.
AB  - The speed and ease of human cytogenetic analysis has been greatly enhanced by the
      technique of fluorescence in situ hybridization (FISH). Non-radioactive
      fluorescently tagged complex DNA probes specific for individual chromosomes can
      be hybridized to conventionally obtained metaphase chromosome spreads. Several
      chromosomes may be "painted" concurrently by using combinations of different
      labeled probes. Surveys of chromosome breakage and rearrangement may be performed
      very quickly by avoiding the time consuming process of GTG-banding. The
      application of FISH to mouse cytogenetics would allow large scale molecular
      toxicology studies to be conducted on the effects of such environmental insults
      as potential carcinogens, mutagens and radiation. Progress has been hampered,
      however, as the Mus musculus karyotype consists of 40 acrocentric chromosomes of
      approximately the same size, making the recognition and separation of individual
      chromosomes very difficult. We now describe the successful production and
      application of chromosome-specific composite DNA probes for M. musculus
      chromosomes 2 and 8. Stable Robertsonian translocated chromosomes were isolated
      on a flow sorter and their DNA subsequently amplified by degenerate
      oligonucleotide primer (DOP) PCR. Small pools (300 copies) of each chromosome
      were denatured at 94 degrees C then annealed with the primer at 30 degrees C for
      15 cycles. This was followed by 20 cycles at an annealing temperature of 62
      degrees C. Additional amplification was performed at an annealing temperature of
      62 degrees C. The chromosome-specific DNA was labeled with biotin 11-dUTP by nick
      translation and used for FISH. The usefulness of the technique for translocation
      detection is demonstrated by analyzing chromosome exchanges induced in mice
      irradiated with 137Cs gamma rays.

PMID- 7508364
TI  - Risperidone and remoxipride for schizophrenia.

PMID- 7508365
TI  - Embryonic mesodermal defects in alpha 5 integrin-deficient mice.
AB  - A loss of function mutation of the murine alpha 5 integrin gene generated by gene
      targeting in embryonic stem cells is a recessive embryonic lethal. The mutant
      embryos start to show observable defects by day 9 of gestation and die around day
      10-11. The alpha 5-null embryos have pronounced defects in posterior trunk and
      yolk sac mesodermal structures, suggesting a role for alpha 5 beta 1 integrin in
      mesoderm formation, movement or function. However, the embryos progress
      significantly further than embryos null for fibronectin, for which alpha 5 beta 1
      integrin is a receptor, suggesting the involvement of other fibronectin
      receptors. In vitro studies on cells derived from the alpha 5-null embryos
      confirm that the alpha 5 beta 1 integrin is not expressed on mutant cells and
      show that the mutant cells are able to assemble fibronectin matrix, form focal
      contacts, and migrate on fibronectin despite the complete absence of the alpha 5
      beta 1 fibronectin receptor integrin. All these functions have previously been
      thought to involve or require alpha 5 beta 1. The results presented show that
      these cellular functions involving fibronectin can proceed using other receptors.

PMID- 7508367
TI  - Valid identification of blink artefacts: are they larger than 50 microV in EEG
      records?
AB  - Can artefacts, in particular of blink potentials, be validly identified in EEG
      data by defining EEG amplitudes as artefacts whenever their absolute values
      exceed 50 microV? Does the performance of this 50 microV criterion change when
      the data have been high-pass filtered (simulating a low time constant)? These
      questions were studied in data of an auditory oddball task recorded from young
      and elderly healthy adults and from Alzheimer patients. The performance of the 50
      microV criterion heavily depended on the distance from the eyes: most blinks were
      detected at Fz, very few at Pz and Oz. This rate further decreased after high
      pass filtering. A qualitative effect of the 50 microV criterion occurred in the
      Alzheimer patients' Pz data: unidentified blink artefacts caused a late positive
      wave that mimicked a delayed P3. In the high-pass filtered data, this effect
      occurred not only at Pz but also at Cz. These results lead to the conclusion that
      the 50 microV criterion does not in general perform well, and in particular may
      bias results when records are made from Pz or from Cz only using a short time
      constant.

PMID- 7508366
TI  - Viewing speed and frequency resolution in digital EEG.
AB  - This study of viewing speed and frequency resolution of a digital
      electroencephalograph (EEG) system explains how, in spite of limited video
      monitor resolution, technological advances permit digital EEG presently to
      approach paper EEG performance, and in the foreseeable future to exceed it.
      Analyses of aspects of eye and brain physiology and elements of digital
      technology reveal how an image traditionally inscribed on paper can be displayed
      on a video monitor so that viewing and interpretation are as quick and accurate
      as on paper. Results are compared to standards set by capabilities of the eye and
      paper EEG.

PMID- 7508368
TI  - Automatic EEG spike detection: what should the computer imitate?
AB  - We conducted a study to explore how electroencephalographers (EEGers) read EEGs
      and reach clinical impressions based upon them. Eight EEGers and a rule-based
      computerized "spike" detector marked epileptiform discharges ("EDs") in 12 test
      records. Of all marked events, 18% were marked by all readers and 38% were marked
      by only one reader. Readers agreed on basic clinical features of the records,
      such as whether a record demonstrated EDs, the rank order of ED sources by
      location, and the ranking of test records in order of the number of EDs detected.
      Readers marked records in a consistent pattern that was independent of an
      objective measure of expertise and experience. Our computerized ED detector had
      lower sensitivity and selectivity than human readers, but either parameter could
      be adjusted to be comparable to human EEGers at the expense of the other. We
      propose that EEGers employ reproducible, quantitatively different styles of
      reading EEG tracings to reach qualitatively similar clinical impressions. In
      practice, EDs are not absolutely defined, but appear to represent a continuum of
      activity which lends itself better to description and rank ordering than to
      absolute quantitation. More than just counting EDs, a successful computerized ED
      detector should be adaptable to the style of individual readers in order to help
      them efficiently formulate their clinical impressions.

PMID- 7508369
TI  - Epileptiform activity during opioid anesthesia.
AB  - The proconvulsant properties of exogenously administered opioids in man are not
      established. We prospectively evaluated relationships between epileptiform
      activity and opioid dose in 20 patients undergoing coronary artery
      revascularization. Baseline electroencephalograms were performed before surgery.
      Ten subjects were given fentanyl and 10 sufentanil, at 100 micrograms/kg and 10
      micrograms/kg, respectively, in 4 divided doses, 3 min apart. Midazolam (4 mg)
      was given 3 min after the last dose of narcotic. Serum opioid concentrations were
      measured by radioimmunoassay. Within 3 min of the first opioid dose, 19 of 20
      patients developed epileptiform activity, characterized by generalized single and
      multiphasic, low-to-moderate voltage spike discharges, similar in appearance to
      benign epileptiform transients of sleep (BETS). Despite continuously increasing
      serum concentrations of opioid, the number of spike discharges initially
      increased during the first and second dose intervals and then declined during the
      third and fourth dose intervals. This dissociation between epileptiform
      discharges and measured serum opioid concentration was unexpected and remained
      unexplained. Spike activity was consistently attenuated (P = 0.000003) within 20
      sec of midazolam administration. Abrupt cessation of discharges after
      administration of the anticonvulsant, midazolam, suggests an epileptogenic
      mechanism for the opioid-induced activity.

PMID- 7508370
TI  - A data acquisition system for long-term monitoring of physiological and video
      signals.
AB  - We developed a system for interleaving digitized physiological signals and video
      images of subjects onto digital media in a standard file format. The system
      consists of a framegrabber used to digitize video signals, a microcomputer used
      to digitize analog signals and send the resulting signals over a parallel
      interface, and a host laboratory computer to gather and store the video and
      analog data in an interleaved format as a single file. The system allows for
      digital storage, search and display of video signals concurrently with
      physiological signals.

PMID- 7508371
TI  - Regional differences in brain electrical activity in dementia: use of spectral
      power and spectral ratio measures.
AB  - The pathologic changes in dementia of the Alzheimer's type (DAT) commonly affect
      selected brain regions. The cortical areas affected in multi-infarct dementia
      (MID) are less predictable and may be secondary to subcortical gray or white
      matter damage that is widespread in MID. We compared several types of
      quantitative EEG power measures (absolute and relative power, and ratios of
      power) to determine their regional distribution, and their association with
      changes in cognitive status and age. We examined 49 subjects with clinically
      diagnosed mild-to-moderate DAT, 29 with mild-to-moderate MID, and 38 elderly
      controls (CON). We used discriminant analysis to identify, for each parameter
      type, the brain region and frequency band where the parameter best distinguished
      between groups of subjects. The parameters showed regional differences in
      distinguishing between DAT and MID subjects, and in their association with age
      and cognitive status. All parameters were useful for detecting differences
      between normal and demented subjects and correctly identified comparable
      proportions of subjects as having dementia. Subjects who were abnormal on several
      parameters were much more likely to have dementia. The additive effects of these
      parameters in correct classification suggest that they may be monitoring
      different physiologic processes. Combinations of several types of parameters may
      be more useful than individual parameters for distinguishing demented from non
      demented subjects.

PMID- 7508372
TI  - Electrical source analysis of auditory ERPs in medial temporal lobe amnestic
      syndrome.
AB  - Auditory event-related potential (ERP) components have been anatomically linked
      to temporal lobe structures and functionally related to attentional and memory
      processes. We recorded auditory ERPs using an "oddball" paradigm from two
      patients with amnestic syndromes secondary to medial temporal lobe encephalitic
      infections. The oddball paradigm elicits the exogenous N1 and P2 components, and
      the endogenous N2 and P3 components. Electrical source analysis was used to test
      for alterations in source strength and orientation in these patients compared to
      control subjects. Symmetric dipoles placed in the temporal lobe region were used
      to measure ERP component activity. In the patient with a lesion confined to the
      left, medial temporal lobe, including the posterior hippocampus, dipole
      orientation was displaced anteriorally. In the patient with lesions to the
      anterior medial temporal lobe, temporal poles, and orbital frontal cortex, the
      negative components of the ERP (N1 and N2) were reduced in the right hemisphere,
      accompanied by disturbed orientation. These findings are consistent with other
      evidence that the different components of the auditory ERP can be dissociated on
      the basis of lesion effects, and that the antero-posterior extent of encephalitic
      lesions may play an important role in modulating ERP abnormalities.

PMID- 7508373
TI  - Median method for detecting endogenous event-related brain potentials.
AB  - Most studies of event-related brain potentials (ERPs) use the averaging method.
      This procedure is assumed to increase signal/noise ratio in proportion to the
      square root of the number of trials if the signal is invariant and the noise is
      stationary. In addition, the averaged value is the appropriate measure of central
      tendency if the measurements have a Gaussian distribution. For endogenous ERPs,
      however, application of the averaging method encounters 3 serious problems.
      First, the invariance of signal cannot always be assumed because the endogenous
      signal reflects psychological processes which may be missing in some trials.
      Secondly, the Gaussian distribution cannot be assumed when a small number of
      trials is averaged. Thirdly, averaging a limited number of trials is sensitive to
      inclusion of occasional, non-random, noise. The characteristics of the median ERP
      can address all 3 problems. These characteristics are demonstrated by an original
      equation.

PMID- 7508374
TI  - A comparison of the localization of spontaneous neuromagnetic activity in the
      frequency and time domains.
AB  - We investigated the localization of current sources for spontaneous
      magnetoencephalographic data in the frequency and time domains. The two analysis
      techniques yielded complementary information about the underlying neuronal
      generators. Phase-coherent sources for occipital 10 Hz alpha band activity were
      identified in the frequency domain from the dependence of the equivalent current
      dipole strengths on the phase of the Fourier transform. Source localization in
      both the frequency and time domains was used to analyze data containing
      interictal spike and slow-wave activity. Predominantly 2-6 Hz spectral components
      localized in the frequency domain were found within an 8 cm3 volume centered at
      the time-domain source location of the spike. In general, the characteristics of
      the noise sources in magnetoencephalographic systems favor the use of frequency
      domain analysis for rhythmic spontaneous activity.

PMID- 7508375
TI  - Monitoring the patient's EEG during echo planar MRI.
AB  - The recording of an EEG while the patient is undergoing magnetic resonance
      imaging (MRI) data acquisition, as far as we are aware, has not been previously
      accomplished. By careful selection and arrangement of analog multiplexed cable
      telemetry equipment to eliminate both ferrous and RF sources, a stable, readable
      EEG can be obtained without interfering with the diagnostic quality of the MRI.
      This arrangement does not cause localized heating or burning at the electrode
      sites. This technical capability permits more accurate neurophysiological control
      during the acquisition of echo planar functional MRI studies as well as providing
      indications of anatomical localization of electrical sources.

PMID- 7508376
TI  - Recommended standards for electroretinograms and visual evoked potentials. Report
      of an IFCN committee.

PMID- 7508377
TI  - Long-term monitoring for epilepsy. Report of an IFCN committee.

PMID- 7508379
TI  - Effects of metoclopramide on the paradoxical growth hormone response to galanin
      in acromegaly.
AB  - Galanin is able to enhance growth hormone (GH)-releasing hormone stimulated GH
      secretion in normal man. In acromegaly circulating GH levels are elevated and the
      GH response to GHRH may be exaggerated. Galanin has been recently shown to
      decrease circulating GH levels in acromegaly. Dopaminergic drugs were the only
      previously known agents able to cause a paradoxical GH fall in acromegaly. Aim of
      our study was to investigate the effects of a potent central dopaminergic
      receptor blocker, metoclopramide (MCP), on the galanin-induced paradoxical GH
      secretion in acromegalic subjects. Two male and three female patients with active
      acromegaly (age range 44-66 years, body mass index range 24.6-28 Kg/m2) were
      studied after 45 min i.v. infusion of porcine galanin (0.5 mg in 100 ml of
      saline) from 0 to 45 min combined with a 60 min i.v. infusion of a) saline (100
      ml) or b) MCP (10 mg in 100 ml of saline) from -15 to 45 min. After galanin, GH
      values fell from baseline (27.5 +/- 10 micrograms/L) to a mean nadir of 16.4 +/-
      6.1 micrograms/L; after galanin + MCP, circulating GH levels were also decreased
      (mean nadir 17.3 +/- 8.1 micrograms/L) in all the patients with respect to
      baseline (23.6 +/- 9.7 micrograms/L). No significant differences were found in
      absolute or percent of baseline GH levels after galanin+saline vs galanin + MCP.
      Our results suggest that the paradoxical GH fall after galanin in acromegalic
      patients is not mediated through dopaminergic receptor. It can be hypothesized
      that galanin may interact at the pituitary level with its own receptors expressed
      by GH-secreting adenomatous cells.

PMID- 7508378
TI  - Genistein augments cyclic adenosine 3'5'-monophosphate(cAMP) accumulation and
      insulin release in MIN6 cells.
AB  - Effects of genistein on insulin release were studied using MIN6 cells, a glucose
      sensitive insulinoma cell line. At the non-stimulatory concentrations of glucose,
      genistein did not affect insulin release, however, at the stimulatory
      concentrations of glucose, genistein significantly increased insulin release in a
      dose-dependent manner up to 20 micrograms/ml. The content of cAMP in MIN6 cells
      was also elevated significantly by genistein and the dose-response relationship
      between the genistein and cAMP accumulation was consistent with the relationship
      between the genistein and insulin release. These effects were inhibited by
      calcium antagonists or by the omission of extracellular calcium.
      Isobutylmethylxanthine (IBMX;0.1mM) increased both cAMP accumulation and insulin
      release in MIN6 cells and there were no additive effects by the addition of
      genistein. The accumulation of cAMP might have, at least in part, resulted from
      phosphodiesterase inhibition by genistein. These results suggest that genistein
      augments glucose-induced insulin release by the contribution of cAMP accumulation
      and calcium modulation which depends on extracellular calcium.

PMID- 7508380
TI  - Intracellular trafficking and activation of the furin proprotein convertase:
      localization to the TGN and recycling from the cell surface.
AB  - Furin is a membrane-associated endoprotease that efficiently cleaves precursor
      proteins on the C-terminal side of the consensus sequence, Arg-X-Lys/Arg-Arg1,
      and has been proposed to catalyze these reactions in both exocytic and endocytic
      compartments. To study its biosynthesis and routing, a furin construct
      (designated fur/f) containing the FLAG epitope tag inserted on the C-terminal
      side of the enzyme's autoproteolytic maturation site was used. Introduction of
      the epitope tag had no effect on the expression, proteolytic maturation or
      activity of furin. Analysis of the localization of fur/f by immunofluorescence
      microscopy showed that its staining pattern largely overlapped with those of
      several Golgi-associated markers. Treatment of cells with brefeldin A caused the
      fur/f distribution to collapse around the microtubule organizing center,
      indicating that furin is concentrated in the trans-Golgi network (TGN).
      Immunoelectron microscopy showed unequivocally that furin resides in the TGN
      where it colocalized with TGN38. In agreement with its proposed activity in
      multiple compartments, antibody uptake studies showed that fur/f cycles between
      the cell surface and TGN. Furthermore, targeting to the TGN requires sequences in
      the cytoplasmic tail of the enzyme. Pulse-chase and immunofluorescence analyses
      demonstrated that proregion removal occurs in the endoplasmic reticulum and that
      cleavage may be required for exist from this compartment. Finally, we show that
      proregion removal is necessary but not sufficient for enzyme activation.

PMID- 7508382
TI  - Dephosphorylation of phosphopeptides by calcineurin (protein phosphatase 2B).
AB  - 38 (6-32 residues) enzymically phosphorylated synthetic peptides have been
      assayed as substrates for calcineurin, a Ca2+/calmodulin-dependent protein
      phosphatase (PP-2B) belonging to the family of Ser/Thr-specific enzymes but also
      active on phosphotyrosine residues. Many peptides reproduce, with suitable
      modifications, naturally occurring phosphoacceptor sites. While protein
      phosphatases 2A and 2C are also very active on short phosphopeptides, an extended
      N-terminal stretch appears to be a necessary, albeit not sufficient, condition
      for an optimal dephosphorylation, comparable to that of protein substrates, of
      both phosphoseryl and phosphotyrosyl peptides by calcineurin. This finding
      corroborates the view that higher-order structure is an important determinant for
      the substrate specificity of calcineurin. However, a number of shorter peptides
      are also appreciably dephosphorylated by this enzyme, their efficiency as
      substrates depending on local structural features. All the peptides that are
      appreciably dephosphorylated by calcineurin contain basic residue(s) on the N
      terminal side. A basic residue located at position -3 relative to the
      phosphorylated residue plays a particularly relevant positive role in determining
      the dephosphorylation of short phosphopeptides. Acidic residue(s) adjacent to the
      C-terminal side of the phosphoamino acid are conversely powerful negative
      determinants, preventing the dephosphorylation of otherwise suitable peptide
      substrates. However, calcineurin displays an only moderate preference for
      phosphothreonyl peptides which are conversely strikingly preferred over their
      phosphoseryl counterparts by the other classes of Ser/Thr-specific protein
      phosphatases. Moreover calcineurin does not perceive as a strong negative
      determinant the motif Ser/Thr-Pro in peptides where this motif prevents
      dephosphorylation by the other classes of Ser/Thr protein phosphatases. Whenever
      tested on phosphotyrosyl peptides, calcineurin exhibits a specificity which is
      strikingly different from that of T-cell protein tyrosine phosphatase, a bona
      fide protein tyrosine phosphatase. In particular while the latter enzyme is
      especially active toward a number of phosphopeptides reproducing the
      phosphoacceptor sites of src products and of calmodulin whose N-terminal moieties
      are predominantly acidic, the artificial substrate phospho-angiotensin II,
      bearing an arginine residue at position -2, is far preferred by calcineurin over
      all phosphotyrosyl peptides of similar size. Collectively taken these results
      show that the specificity of calcineurin, rather than resting on a given
      consensus sequence, is determined by a variety of primary and higher-order
      structural features conferring to it an overall selectivity that is different
      from those of any other known protein phosphatase.

PMID- 7508381
TI  - RNA annealing activities in HeLa nuclei.
AB  - RNA-RNA base pairing plays a critical role in the interactions between pre-mRNAs
      and trans-acting factors during the processing of pre-mRNAs (hnRNAs) into mRNAs,
      and it is likely that specific factors are required to promote the annealing of
      RNAs. To identify particular nuclear components that have such activity, we
      fractionated HeLa nucleoplasm and assayed for activity which promoted the
      hybridization of a pre-mRNA with an antisense RNA probe complementary to 60
      nucleotides (nt) encompassing the 3' splice site. At least nine major RNA
      annealing activities were identified and, surprisingly, eight of these copurified
      partially or to homogeneity with known hnRNP proteins. The activities of three of
      these proteins, hnRNP A1, C1 and U, were confirmed using purified recombinant
      proteins. Moreover, we found that the RNA binding domain alone of hnRNP C1/C2 had
      significant activity, indicating that this RNA annealing may result, at least
      partly, from chaperone activity: a direct modulation of RNA conformation by hnRNP
      proteins. The finding that hnRNP proteins have strong RNA annealing activity
      indicates that they can profoundly affect the interactions of pre-mRNAs with
      trans-acting factors and suggests this to be an important function of hnRNP
      proteins in the processing of pre-mRNAs.

PMID- 7508383
TI  - Antagonism of the intracellular action of botulinum neurotoxin type A with
      monoclonal antibodies that map to light-chain epitopes.
AB  - mAbs were produced in mice against highly purified, renatured light chain (LC) of
      botulinum neurotoxin A (BoNT A) that was immobilised on nitrocellulose to avoid
      the undesirable use of toxoids. Subcutaneous implants of relatively high amounts
      (up to 10 micrograms each) of LC allowed its slow release into the systemic
      circulation and, thus, yielded much higher antibody titres against the
      underivatized antigen than had hitherto been obtained by conventional
      immunization. Seven stable hybridoma cell lines were established which secrete
      mAb of IgG1 and IgG2b subclasses reactive specifically with BoNT A and LC, in
      native and denatured states, without showing any cross-reactivity with types B,
      E, F or tetanus toxin. The pronounced reactivities of three mAbs towards refolded
      LC or intact toxin, observed in immunobinding and precipitation assays, relative
      to that seen in Western blots imply a preference for conformational epitopes.
      Though mAbs 4, 5 and 7 failed to neutralize the lethality of BoNT in vivo,
      administration intraneurally of mAb7 prevented the inhibition of transmitter
      release normally induced by subsequent extracellular administration of BoNT A.
      Notably, the latter mAb reacted with a synthetic peptide corresponding to amino
      acids 28-53 in the N-terminus of the LC, a highly conserved region in Clostridial
      neurotoxins reported to be essential for maintaining the tertiary structure of
      the chain. Most importantly, when mAbs 4 or 7 were microinjected inside
      ganglionic neurons of Aplysia, each reversed, though transiently, the blockade of
      acetylcholine release by the toxin; this novel finding is discussed in relation
      to the nature of the zinc-dependent protease activity of the toxin.

PMID- 7508384
TI  - RNAs and ribonucleoproteins in recognition and catalysis.

PMID- 7508385
TI  - Cloning and expression of cDNA of human delta 4-3-oxosteroid 5 beta-reductase and
      substrate specificity of the expressed enzyme.
AB  - The enzyme delta 4-3-oxosteroid 5 beta-reductase (3-oxo-5 beta-steroid: NADP+
      oxidoreductase and 4,5 beta-dihydrocortisone: NADP+ delta 4-oxidoreductase)
      catalyzes the reduction of the delta 4 double bond of bile acid intermediates and
      steroid hormones carrying the delta 4-3-one structure in the A/B cis
      configuration. Human delta 4-3-oxosteroid 5 beta-reductase cDNA was isolated from
      a liver cDNA library by cross hybridization with a previously cloned rat cDNA,
      which was used as a probe [Onishi, Y. Noshiro, M., Shimosato, T. & Okuda, K.-I.
      (1991) FEBS Lett. 283, 215-218]. DNA sequence analysis of a hybridization
      positive clone predicted the human delta 4-3-oxosteroid 5 beta-reductase to
      contain 326 amino acids. The amino acid sequence of the human delta 4-3
      oxosteroid 5 beta-reductase had 79% overall identity to the rat enzyme sequence.
      It also showed 54% and 50% overall identity with rat 3 alpha-hydroxysteroid
      dehydrogenase and human aldose reductase, respectively. RNA blotting analysis
      demonstrated the existence of a single delta 4-3-oxosteroid 5 beta-reductase mRNA
      of approximately 2.7 kb in human liver. Transfection of the cDNA into COS cells
      resulted in the expression of an active enzyme with a high activity toward the
      bile acid intermediates 7 alpha,12 alpha-dihydroxy-4-cholesten-3-one and 7 alpha
      hydroxy-4-cholesten-3-one. In addition, the expressed enzyme showed a small but
      significant 5 beta-reduction activity toward 11 beta,17 alpha,21-trihydroxy-delta
      4-pregnene-3,20-dione (cortisol) and 17 beta-hydroxy-delta 4-androsten-3-one
      (testosterone) whereas no activity was observed toward delta 4-pregnene-3,20
      dione (progesterone) or delta 4-androstene-3-17-dione (androstenedione). The
      substrate specificity of the human enzyme is considerably narrower than that of
      the rat enzyme, and the enzyme seems to be more important for bile acid
      biosynthesis than for metabolism of steroid hormones.

PMID- 7508386
TI  - Contribution of phospholipases A2 and D to arachidonic acid liberation and
      prostaglandin D2 formation with increase in intracellular Ca2+ concentration in
      rat peritoneal mast cells.
AB  - The contribution of phospholipases A2 (PLA2) and D (PLD) activation to
      arachidonic acid liberation and prostaglandin D2 (PGD2) formation was studied in
      stimulated rat peritoneal mast cells. Stimulation of the cells with ionomycin
      induced time-dependent and Ca(2+)-concentration-dependent increase in arachidonic
      acid liberation and PGD2 formation, and the Ca(2+)-dependent increase was
      especially remarkable at extracellular Ca2+ concentration higher than 200 microM.
      Staurosporine did not induce any effect on the arachidonic acid liberation,
      indicating that protein kinase C is not involved in the liberation. Addition of
      ethanol to the cells decreased the ionomycin-stimulated arachidonic acid
      liberation to 40% of the control, while it decreased the PGD2 formation almost
      completely, with the increase in phosphatidylethanol formation. Propranolol, a
      phosphatidate phosphohydrolase inhibitor, caused similar effects. p-Bromophenacyl
      bromide, a PLA2 inhibitor, inhibited partially the arachidonic acid liberation.
      The inhibition of the liberation by combination of p-bromophenacyl bromide and
      ethanol was additive and reached approximately 90%. Under the conditions used p
      bromophenacyl bromide did not influence significantly the PLD activity assessed
      by the phosphatidylethanol formation. Histamine release was decreased by ethanol
      treatment to 35% of the control. These results suggest that more than half of the
      total arachidonic acid liberation is mediated by the sequential pathway of
      PLD/phosphatidate phosphohydrolase/diacylglycerol lipase and more than half of
      histamine release is also dependent on PLD activation, while the PGD2 formation
      is fully mediated by the pathway. PLA2 also contributes to arachidonic acid
      liberation but to a lower extent.

PMID- 7508387
TI  - Hordothionins inhibit protein synthesis at the level of initiation in the wheat
      germ system.
AB  - The inhibitory effect of pure alpha and beta hordothionins on protein synthesis
      directed by pea mRNA has been studied in the wheat-germ translation system. It is
      demonstrated that a component of the wheat germ counteracts the thionin effect.
      Formation of polysomes in vitro in the presence of thionin was inhibited to the
      same extent as the total translation system while run-off translation of isolated
      polysomes from pea plants was not affected by thionin. These data are consistent
      with an effect of thionin on the initiation reaction. Analyses of the formation
      of initiation complexes in the presence and absence of mRNA support this view and
      show that thionin interferes with the formation of the 43S complex. In accordance
      with this observation and in contrast to earlier studies no evidence has been
      obtained for a direct interaction between mRNAs and thionins. The analysis of the
      translation products also gave no indication for preferential translation of
      individual mRNAs by the thionin-inhibited translation system. Compared to
      translation in vitro, exposure of barley protoplasts to thionins showed a less
      dramatic effect on protein synthesis as measured by incorporation of
      [35S]methionine into proteins. These data are discussed with respect to the
      effects of thionins on the plasma membranes as shown previously with animal cell
      cultures. It is concluded that at least in barley such effects would need higher
      concentrations of thionins than are required for the inhibition of protein
      synthesis.

PMID- 7508388
TI  - Nitric oxide reductase from Pseudomonas stutzeri. Primary structure and gene
      organization of a novel bacterial cytochrome bc complex.
AB  - Nitric oxide (NO) reductase is an integral membrane component of the anaerobic
      respiratory chain of Pseudomonas stutzeri that transforms nitrate to dinitrogen
      (denitrification). The enzyme catalyzes the reduction of NO to nitrous oxide. The
      structural genes for the NO reductase complex, norC and norB, were sequenced and
      their organization established by primer extension and Northern blot analysis.
      The norCB genes encoding the cytochrome c and cytochrome b subunits of the enzyme
      are contiguous and transcribed as a single 2.0-kb transcript. The promoter region
      has a canonical recognition motif for the transcriptional activator protein Fnr,
      centered at -40.5 nucleotides from the initiation site of transcription. No
      similarity of the derived gene products to known cytochromes of b- or c-type was
      found in a data bank search. Post-translational processing of the two subunits
      was limited to the removal of the terminal methionine to leave an N-terminal
      serine in either subunit. The mature cytochrome c subunit (16508Da, 145 residues)
      is predicted to be a bitopic protein with a single membrane anchor. The mature
      cytochrome b subunit (53006Da, 473 residues) is a putatively polytopic, strongly
      hydrophobic membrane-bound protein with 12 potential transmembrane segments.
      Several histidine and proline residues were identified with potentially
      structural and/or functional importance. Mutational inactivation of NO reductase
      by deletion of norB or the norCB genes affected strongly the in vivo activity of
      respiratory nitrite reductase (cytochrome cd1), but to a much lesser extent the
      expression level of this enzyme. In turn, mutational inactivation of the
      structural gene for cytochrome cd1, nirS, or loss of in vivo nitrite reduction by
      mutation of the nirT gene, encoding a presumed tetraheme cytochrome, lowered the
      expression level of NO reductase to 5-20%, but hardly its catalytic activity. The
      cellular concentration of NO reductase increased again on restoration of nitrite
      reduction in the nirS::Tn5 mutant MK202 by complementation with nirS or with the
      heterologous nirK gene, encoding the Cu-containing nitrite reductase from
      Pseudomonas aureofaciens. Thus, NO may be required as an inducer for its own
      reductase. Our results show that the nitrite-reducing system and the NO-reducing
      system are not operating independently from each other but are interlaced by
      activity modulation and regulation of enzyme synthesis.

PMID- 7508389
TI  - Cyclic AMP regulation of messenger RNA level of the stimulatory GTP-binding
      protein Gs alpha. Isoproterenol, forskolin and 8-bromoadenosine 3':5'-cyclic
      monophosphate increase the level of Gs alpha mRNA in cultured astroglial cells.
AB  - The existence of a cAMP-dependent regulation of the expression of the alpha
      subunit of the stimulatory guanine nucleotide-binding protein (Gs) in a well
      characterized astroglial cells culture was established. The culture of astroglial
      cells for 3-6 h with isoproterenol (10 microM) or forskolin (10 microM) (a cAMP
      inducing agent) increased (200-400%) the response of adenylylcyclase to agents
      which bypass the receptor; GTP, GTP[S] or forskolin. For prolonged exposure times
      (15 h or more) to isoproterenol or forskolin, the adenylycyclase activity
      decreased to the value observed in control cells. The same biphasic response of
      adenylylcyclase to isoproterenol (10 microM) plus GTP (10 microM) occurred in
      membrane fractions from cells cultured with forskolin, whereas a diminished
      response to isoproterenol was observed in isoproterenol-treated cells, indicating
      that the beta-adrenergic receptor was desensitized. To understand the molecular
      mechanism of these phenomena, we measured the levels of the alpha subunits of the
      guanine-nucleotide binding protein (Gs and Gi) by Western-blot analysis. The
      culture of astroglial cells with isoproterenol or forskolin (3-24 h) resulted in
      a transient increase of both the Gs alpha and the Gi alpha protein levels, while
      the level of G beta subunits was unaffected. We also identified Gs alpha protein
      (about 40% of the total cellular protein) in the supernatant fraction of
      astroglial cells but its level was not modified by the stimulation of cells by
      forskolin. The level of Gs alpha mRNA measured by Northern-blot analysis was
      transiently increased (200%) after stimulation of astroglial cells with
      isoproterenol or forskolin for an incubation period of 6-9 h, then returned to
      that of control cells for longer period of time. In addition, the Gs alpha mRNA
      level was threefold increased when cells were cultured for 2-6 h with 8
      bromoadenosine 3':5'-cyclic monophosphate (10 microM), a permeant analogue of
      cAMP. These results indicate that cAMP induces a time-dependent increase of Gs
      alpha mRNA. The half-life of Gs alpha protein and Gs alpha mRNA were determined.
      Pulse-chase studies revealed that the decay of Gs alpha protein was clearly
      biphasic with an early phase (5-6 h) and a slower second phase (20-25 h) but the
      treatment of cells with forskolin did not accelerate or slow down the turnover of
      Gs alpha protein.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7508391
TI  - Inducible nitric-oxide-synthase mRNA is transiently expressed and destroyed by a
      cycloheximide-sensitive process.
AB  - Nitric oxide is a mediator of a wide range of physiological processes. It is
      produced by an enzyme family, the nitric-oxide synthases, one form of which is
      induced in many cells following stimulation with cytokines and
      lipopolysaccharide. The aim of the experiments reported in this study was to
      investigate the regulation of mRNA expression for this inducible nitric-oxide
      synthase in smooth muscle cells and macrophages. Stimulation of these cells with
      cytokines and lipopolysaccharide results in a marked elevation of nitric-oxide
      synthase mRNA levels, which however do not remain elevated, but reach a maximum
      at 3-6 h after stimulation before returning to baseline levels over the next 20
      h. Enzyme activity, however, remained virtually constant for 48 h following
      stimulation. Inspection of the 3' untranslated segment of both murine and human
      inducible nitric-oxide-synthase mRNAs showed the presence of a conserved AU-rich
      octanucleotide sequence, previously identified in cytokine and oncogene mRNAs and
      shown to mediate mRNA instability. A particular feature of the breakdown of mRNAs
      bearing this sequence is that degradation is prevented by protein-synthesis
      inhibition. We show in this study that the half-life of inducible nitric-oxide
      synthase mRNA is 6 h and that in the presence of an inhibitor of protein
      synthesis this breakdown is prevented. Thus, the mRNA for inducible nitric-oxide
      synthase shares some features in common with cytokines such as the transient
      expression and decay of its mRNA which can be prevented by protein-synthesis
      inhibition.

PMID- 7508390
TI  - Induction of lactase biosynthesis in the human intestinal epithelial cell line
      Caco-2.
AB  - The human colonic adenocarcinoma cell line Caco-2 forms monolayers of
      differentiated enterocyte-like cells when cultured on permeable supports. After
      confluency, Caco-2 cells express a number of brush-border enzymes including
      lactase-phlorizin hydrolase, sucrase-isomaltase and dipeptidylpeptidase IV. We
      have studied, with particular emphasis on lactase-phlorizin hydrolase, the
      modulation of biosynthesis of these enzymes by stimulating second messenger
      systems. Forskolin induced lactase-phlorizin hydrolase synthesis approximately
      fourfold within 7 h, suppressed sucrase-isomaltase synthesis, and had little
      effect on dipeptidylpeptidase IV. Dibutyryl-cAMP, 8-bromo-cAMP and vasoactive
      intestinal peptide also increased lactase-phlorizin hydrolase biosynthesis,
      indicating c-AMP dependent regulation. The induction of lactase-phlorizin
      hydrolase biosynthesis could be inhibited by actinomycin D and was preceded by a
      fourfold increase in lactase-phlorizin hydrolase mRNA levels, suggesting
      transcriptional control. Phorbol 12-myristate 13-acetate had an inhibitory effect
      on brush-border enzyme synthesis, in particular on sucrase-isomaltase, and
      blocked the forskolin-induced biosynthesis of lactase-phlorizin hydrolase.
      Lactase-phlorizin hydrolase synthesis was also inducible by hydrocortisone, but
      maximal induction required at least 3 days during which time sucrase-isomaltase
      synthesis diminished. The results indicate opposite regulation of lactase
      phlorizin hydrolase and sucrase-isomaltase via cAMP and corticosteroids, and
      suggest that the Caco-2 cell line can serve as a model system to study aspects of
      the humoral regulation of human intestinal brush-border enzymes in cell culture.

PMID- 7508392
TI  - Characterisation and amino acid sequence of cytochrome c-550 from Thiosphaera
      pantotropha.
AB  - A cytochrome c-550, with mid-point potential +265 mV, has been purified from
      Thiosphaera pantotropha. The cytochrome was recognised by antibodies to
      Paracoccus denitrificans cytochrome c-550, but the two proteins were not
      immunologically identical. Amino acid sequencing of the cytochrome c-550 showed
      85.9% and 95.5% identities, respectively, with the cytochromes c-550 of P.
      denitrificans and Thiobacillus versutus; these are amongst the highest values
      reported for similarities between class I c-type cytochromes of the c2 group.
      These similarities are consistent with the published values of 85% for the
      overall DNA similarity of P. denitrificans and T. pantotropha, but contrast with
      published 16S rRNA analyses which indicate identity between T. pantotropha and P.
      denitrificans and 97.5% similarity of T. versutus with these two organisms.
      Analysis by plasma-desorption mass spectrometry of the peptide containing the
      haem-binding motif isolated from the apocytochrome has shown that an Hg atom
      binds to one or both of the two thiol groups.

PMID- 7508393
TI  - The structure of the O-specific polysaccharide of Citrobacter O16 containing
      glycerol phosphate.
AB  - The O-specific polysaccharide, obtained by mild acid degradation of Citrobacter
      O16 lipopolysaccharide, consists of D-glucose, D-galactose, 2-acetamido-2-deoxy-D
      galactose, glycerol and phosphate in the ratios 2:2:2:1:1. Selective cleavage of
      the polysaccharide was carried out by Smith degradation, N-deacetylation
      deamination and dephosphorylation with 48% hydrofluoric acid, which was
      accompanied by unexpected splitting of one of the glycosidic linkages. The
      structures of the oligosaccharides thus obtained were established using 1H- and
      13C-NMR spectroscopy, including one-dimensional NOE, two-dimensional rotating
      frame NOE, homonuclear and heteronuclear 13C, 1H correlation spectroscopy, and,
      for the Smith degradation product, positive- and negative-ion-mode fast-atom
      bombardment MS and MS/MS with collision-induced dissociation. On the basis of
      these data and the results of methylation analysis, it was concluded that the O
      specific polysaccharide has the following repeating unit structure: [formula: see
      text]

PMID- 7508394
TI  - Circulating autoantibody to mature neurons and astrocytes of humans and some
      mammals present in a demented patient with autoimmune disorder.
AB  - Circulating autoantibody to a 48-kD nuclear protein in neurons and astrocytes of
      the human and bovine cerebrum were present in the serum of a demented patient
      with an autoimmune disorder. Other human visceral organs, dorsal root ganglion
      cells, neuroblastoma and glioblastoma cell lines, and rat cerebrum did not react
      with the patient's serum. No sera from age-matched controls, including those with
      Alzheimer's disease, reacted with the 48-kD protein. Only the mature neurons and
      astrocytes of humans and some mammals express the 48-kD protein. This antibody
      may be responsible for the patient's demented condition.

PMID- 7508395
TI  - Laser ablation of the prostate: experience with an ultrasound guided technique
      and a procedure under direct vision.
AB  - Twenty-four patients with benign prostatic hyperplasia were treated with the
      Nd:YAG laser. We review our experience with two different techniques: the
      ultrasound-guided transurethral laser-induced prostatectomy (TULIP) and the
      visual laser ablation of the prostate (VLAP). Our experience with these two
      different laser systems shows that the treatment is relatively simple, speedy and
      performed with virtually no blood loss. The results, of both the TULIP and VLAP
      procedures, are excellent. The symptom scores decrease from 43 to 19 (TULIP) and
      48 to 9 (VLAP). Furthermore, there is a marked increase in average uroflow from
      7.9 to 18.6 ml/s (TULIP) and from 8.1 to 18.0 ml/s (VLAP). The patients with the
      TULIP procedure, however had more pronounced posttreatment complaints. These
      patients more often received antibiotics. Laser therapy of the prostate, although
      still in its infancy, gives excellent results and has substantial advantages over
      conventional transurethral resection of the prostate (TURP). Laser therapy may
      replace TURP within several years.

PMID- 7508397
TI  - Sodium pentosanpolysulphate in the management of haemorrhagic cystitis:
      experience with 14 patients.
AB  - Haemorrhagic cystitis following radiotherapy is fortunately relatively uncommon.
      When it does present it represents a therapeutic challenge. We have managed 14
      patients with haemorrhagic cystitis of varying severity with sodium
      pentosanpolysulphate. Complete control of haematuria was achieved in 10 patients
      and partial control in 3 patients. This medication is effective, safe and merits
      further investigation.

PMID- 7508396
TI  - Pain sensation in transurethral microwave thermotherapy for benign prostatic
      hyperplasia: the rationale for prophylactic sedation.
AB  - Transurethral microwave thermotherapy (TUMT) can be painful. Pain sensation
      limits treatment tolerance and consequently also treatment efficacy. Of our
      population of patients treated with TUMT, 22% (63/288) needed intravenous
      analgesia and, nevertheless, 6% (17/288) needed definitive treatment
      interruption. The aim of this study was to identify the mechanism of pain
      sensation during TUMT and to verify whether the prophylactic use of a sedative
      drug would improve treatment tolerance. Eighty-three patients undergoing TUMT
      treatment for benign prostatic hyperplasia at our department entered a
      prospective, randomized, single-blinded study. Thirty minutes before treatment,
      40 patients (group A) received 960 mg cotrimoxazole orally while 43 patients
      (group B) received 960 mg cotrimoxazole and 10 mg oxazepam, both orally.
      Statistically significant improvement in treatment tolerance in group B in
      comparison with group A was found. Pain sensation during TUMT seemed to be mostly
      due to anxiety. It is concluded that the prophylactic use of a sedative drug is
      advisable in patients undergoing TUMT in order to improve treatment tolerance.

PMID- 7508398
TI  - Patients with achalasia lack nitric oxide synthase in the gastro-oesophageal
      junction.
AB  - The abnormal function of the lower oesophageal sphincter in achalasia is likely
      to be due to impaired nonadrenergic, noncholinergic (NANC) inhibitory input.
      Since recent studies in animals suggest that nitric oxide (NO) is implicated
      physiologically in the inhibitory responses of the lower oesophageal sphincter,
      we have investigated whether the synthesis of NO is altered in the gastro
      oesophageal junction of patients with achalasia. NO synthase activity was
      investigated in samples of tissue from the gastro-oesophageal junction obtained
      during surgery in eight patients with typical achalasia and six non-achalasic
      controls who underwent oesophagectomy for reasons other than sphincter
      dysfunction. The NO synthase activity was determined by the transformation of 14C
      L-arginine into 14C-L-citrulline in tissue homogenates. In addition,
      immunohistochemical staining of the tissues was performed using a polyclonal
      antibody raised against a peptide sequence of rat brain NO synthase. Furthermore,
      the relaxant response to an exogenous NO donor (sodium nitroprusside, SNP) was
      measured in vitro in muscle strips obtained from two patients with achalasia and
      in two non-achalasic controls. NO synthase activity was detected in each of the
      samples obtained from six control patients (0.59 +/- 0.21 pmol mg-1 min-1; mean
      +/- SE). By contrast, none of the samples obtained from the eight patients with
      achalasia had any detectable NO synthase activity. Immunohistochemical studies
      confirmed the presence of NO synthase in the myenteric plexus of the gastro
      oesophageal junction of control patients and its absence in achalasia. SNP
      relaxed muscle strips precontracted with bethanechol in both control samples and
      those from patients with achalasia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508399
TI  - Inhibition by a receptor-mediated Ca2+ entry blocker, SK&F 96365, of Ca2+ and
      secretory responses in rat pancreatic acini.
AB  - The effect of a receptor-mediated Ca2+ entry blocker, 1-(beta-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F
      96365), on a secretagogue-induced secretory response and Ca2+ dynamics was
      examined in isolated acini of rat pancreas. SK & F 96365 inhibited the secretory
      response induced by 100 pM cholecystokinin octapeptide (CCK-8) or 3 microM
      ethanaminium, 2-[(aminocarbonyl)oxy]-N,N,N-trimethyl,-chloride (carbachol) in
      isolated incubated acini up to 73.2 +/- 6.1% or 70.3 +/- 3.8% with IC50 of 47.7
      microM or 42.0 microM, respectively. The inhibitory effect of SK&F 96365 on the
      time courses of CCK-8-induced amylase release and [Ca2+]c (cytoplasmic Ca2+
      concentration) elevation was further examined in isolated perifused acini or
      isolated acini loaded with Fura-2. In the 100 pM CCK-8-stimulated preparation, 30
      microM SK&F 96365 partly, and 100 microM SK&F 96365 completely, inhibited the
      sustained plateau phase, but did not inhibit the initial phase of the Ca2+ and
      secretory responses. In the 5 pM CCK-8-stimulated preparation; (a) 30 microM SK&F
      96365 reduced the frequency of the [Ca2+]c oscillations, but caused little, if
      any, changes in the secretory response; (b) 100 microM SK&F 96365 transformed the
      oscillatory [Ca2+]c dynamics to a transient increase followed by a gradual decay
      and caused a significant inhibition of the sustained secretory response. These
      results indicate that the sustained responses to secretagogues are dependent on a
      receptor-mediated Ca2+ entry which can selectively be blocked by SK&F 96365 in
      rat pancreatic acini.

PMID- 7508400
TI  - Increased resting Ca2+ maintains the myogenic tone and activates K+ channels in
      arteries from young spontaneously hypertensive rats.
AB  - We examined whether the Ca2+ channel function in the resting state alters the
      resting tone in femoral and carotid arteries from spontaneously hypertensive rats
      (SHR) at early hypertensive stages (6 and 4 weeks of age), and data were compared
      with findings in age-matched normotensive Wistar-Kyoto rats (WKY). Strips of
      femoral and carotid arteries from 6-week-old SHR, but not from WKY, maintained a
      myogenic tone, that is, the resting tone decreased when 10(-7) M nifedipine was
      added. A similar myogenic tone was maintained in 4-week-old SHR. In strips of
      carotid arteries preloaded with fura-2, a fluorescent Ca2+ indicator, the
      decrease in cytoplasmic Ca2+ concentration following 0-Ca2+ solution or 5 x 10(
      7) M nicardipine was significantly greater in SHR than in WKY. The basal 45Ca
      influx in femoral and carotid arteries from 6-week-old SHR was significantly
      increased when compared with WKY, and this increase in SHR was abolished by 10(
      7) M nifedipine. The addition of charybdotoxin (a blocker of large conductance
      Ca(2+)-activated K+ channels) or of Bay k 8644 (an agonist of L-type voltage
      dependent Ca2+ channels; VDCs), caused a concentration-dependent contraction,
      which was significantly greater in 6- and 4-week-old SHR than in WKY. These
      results suggest that the Ca2+ influx via L-type VDCs was increased in the resting
      state of femoral and carotid arteries from SHR at the early hypertensive stages,
      and therefore the myogenic tone was maintained and charybdotoxin-sensitive K+
      channels were highly activated.

PMID- 7508401
TI  - Morphology and growth of embryonic, human dorsal root ganglion explants in long
      term culture: expression of cell type-specific markers during early
      differentiation.
AB  - Embryonic, human spinal ganglion explants were plated at 5-12 weeks
      postconceptional age and cultured for 5-50 days on a semisynthetic substrate in a
      serum-containing culture medium without addition of antibiotics or preconditioned
      medium. The growth pattern in vitro was found to be age dependent. Five- to 6
      week ganglia showed a characteristic semicircular growth pattern with
      bidirectional extension of neurites on top of a monolayer of supportive cells.
      Explanted 9- to 10-week ganglia showed an extensive, multidirectional neurite
      outgrowth with less pronounced proliferation of nonneuronal cells. Neurite
      extension, fasciculation, cell migration and morphology were studied
      immunohistochemically with antibodies to neurofilament (NF), S-100, and the Thy-1
      glycoprotein. Both NF and S-100 were expressed at 5 weeks gestational age in
      ganglionic neurons and in proliferating Schwann cells in contact with axonal
      processes, respectively. NF was homogeneously distributed in both cell somata and
      neurites, whereas S-100 immunoreactivity showed an intense nuclear and a weaker
      cytoplasmic distribution in spindle-shaped, bipolar Schwann cells. This staining
      pattern was conserved during differentiation in long-term culture. Thy-1 was
      expressed on ganglionic neurites forming fascicles by the third week in culture.
      However, Thy-1 was never expressed until the total age of 10 weeks. In addition,
      Thy-1 was found on fibroblasts from the first week in culture. The distribution
      of Thy-1 on the cytoplasmic membrane was similar in both cell types, showing a
      coarsely granulated membrane staining. The temporal as well as the spatial
      expression of differentiation antigens in tissue sections of early embryonic
      spinal cord and spinal ganglia were very similar to what was observed in vitro.

PMID- 7508402
TI  - Alkalinization of acidic cellular compartments following cell swelling.
AB  - Osmotic swelling of rat hepatocytes increases fluorescence of Acridine orange and
      of fluorescein isothiocyanate (FITC)-dextran, both indicative of alkalinization
      of acidic intracellular vesicles. Similar to osmotic cell swelling, insulin and
      glutamine lead to an increase in Acridine orange fluorescence, an effect
      virtually abolished upon osmotic reversal of glutamine-induced cell swelling.
      Barium, which blocks K+ channels in the plasma membrane, similarly leads to cell
      swelling and increase of Acridine orange fluorescence. Since proteolysis is
      governed by lysosomal pH, these observations indicate that the anti-proteolytic
      action of osmotic cell swelling is mediated by lysosomal alkalinization. Thereby,
      insulin, glutamine and barium probably exert their anti-proteolytic action by
      cell swelling and subsequent lysosomal alkalinization.

PMID- 7508403
TI  - Cell differentiation in vitro and the expression of Oct-2 protein and oct-2 RNA.
AB  - Expression of the oct-2 gene was studied in mouse tissues and during in vitro
      differentiation of embryocarcinoma PCC4, mouse neuroblastoma Neuro2A and NB41A3
      cells in the presence of retinoic acid (RA) or 1% DMSO. oct-2 mRNA is
      characterized by a complex pattern and exists in both poly(A)+ and poly(A)-
      forms. oct-2 mRNA was found in many cell lines, whereas Oct-2 protein was
      detected only in some of these cells. oct-2 expression also changed during cell
      differentiation. The cell differentiation is likely to be controlled not only at
      the gene transcription level, but also at the level of regulation of nuclear
      transcription factor activity. Such a regulatory mechanism would provide for a
      finer regulation of cell differentiation.

PMID- 7508404
TI  - Existence of nuclear-encoded 5S-rRNA in bovine mitochondria.
AB  - A number of proteins functioning in mitochondria are synthesized in the cytoplasm
      and imported into the mitochondria via specific transport systems. In mammals, on
      the contrary, mitochondrial membranes have generally been considered to be
      impermeable to nucleic acids. However, here we show that an RNA with 120
      nucleotides, the sequence of which is identical to that of the nuclear-encoded 5S
      RNA, exists in bovine mitochondria, although the mitochondrial genome encodes no
      5S RNA gene. This RNA molecule was found to be retained in purified bovine
      mitochondria as well as in the mitoplasts, even after extensive treatment with an
      RNase, demonstrating that the 5S RNA is actually located inside the mitochondrial
      inner membrane. The 5S rRNA molecule was also shown to exist in mitochondria from
      rabbit and chicken.

PMID- 7508405
TI  - Specificity of protein interactions with highly related SRC homology (SH) domains
      of FGR and FYN protein-tyrosine kinases.
AB  - As an approach toward identification and isolation of cellular proteins that may
      act as substrates or effectors of the SRC-family of protein-tyrosine kinases,
      fusion proteins containing noncatalytic elements of two highly related SRC-family
      members were tested for their ability to recognize distinct molecules present in
      lysates of cells known to normally express both enzymes. Our results demonstrate
      differences of protein binding between the SH2 elements of FYN and FGR kinases,
      but do not discriminate proteins binding to their SH3 domains.

PMID- 7508406
TI  - Different induction mechanisms of mRNA for inducible nitric oxide synthase in rat
      smooth muscle cells in culture and in aortic strips.
AB  - The expression of mRNA for the inducible form of nitric oxide synthase, (iNOS),
      was studied in rat aortic smooth muscle cells, (SMCs) in cell culture and in
      strips of rat aorta by reverse transcriptase coupled to the polymerase chain
      reaction. iNOS mRNA expression was weak in cultured SMCs when exposed to either
      interferon-gamma (IFN gamma) or lipopolysaccharide (LPS), but the combination
      LPS+IFN gamma enhanced the expression. In aortic strips LPS alone induced a
      pronounced expression, with no further increase by IFN gamma. Cycloheximide
      potentiated the expression of iNOS mRNA in SMCs in culture stimulated with
      LPS+IFN gamma but attenuated the response in aortic strips. The results indicate
      different cellular signaling pathways for the induction of iNOS mRNA by LPS
      and/or IFN gamma, in cultured SMCs and in rat aortic strips.

PMID- 7508407
TI  - Enhancement of inducible-type NO synthase gene transcription by protein synthesis
      inhibitors. Activation of an intracellular signal transduction pathway by low
      concentrations of cycloheximide.
AB  - Treatment of mouse macrophage-like RAW 264.7 cells with certain protein synthesis
      inhibitors is followed by accumulation of the mRNA for the inducible isoform of
      nitric oxide synthase (i-NOS). The activity of these compounds on the i-NOS gene
      in RAW 264.7 cells was analyzed here in detail. Results show that both
      cycloheximide and anisomycin can efficiently induce i-NOS mRNA, even when used at
      concentrations so low (0.25 microgram/ml) to have only negligible effects on
      protein synthesis; puromycin, on the other hand, shows only a limited effect on i
      NOS mRNA expression, detectable only when cells are treated with higher
      concentrations of inhibitor (25 micrograms/ml). In RAW 264.7 cells, low
      concentrations of cycloheximide trigger an immediate-early gene response, as
      indicated by induction of c-fos and JE mRNAs, and can efficiently activate
      transcription of transiently transfected recombinant reporter genes including
      either the i-NOS or the c-fos gene promoters.

PMID- 7508408
TI  - A method for calibrating molecular clocks and its application to animal
      mitochondrial DNA.
AB  - A generalized least-squares procedure is introduced for the calibration of
      molecular clocks and applied to the complete mitochondrial DNA sequences of 13
      animal species. The proposed technique accounts for both nonindependence and
      heteroscedasticity of molecular-distance data, problems that have not been taken
      into to account in such analyses in the past. When sequence-identity data are
      transformed to account for multiple substitutions/site, the molecular divergence
      scales linearly with time, but with substantially more variation in the
      substitution rate than expected under a Poisson model. Significant levels of
      divergence are predicted at zero divergence time for most loci, suggesting high
      levels of site-specific heterozygosity among mtDNA molecules establishing in
      sister taxa. For nearly all loci, the baseline heterozygosity is lower and the
      substitution rate is higher in mammals relative to other animals. There is
      considerable variation in the evolutionary rate among loci but no compelling
      evidence that the average rate of mtDNA evolution is elevated with respect to
      that of nuclear DNA. Using the observed patterns of interspecific divergence,
      empirical estimates are derived for the mean coalescence times of organelles
      colonizing sister taxa.

PMID- 7508409
TI  - [Interferon as a stimulator of DNA repair in patients with xeroderma
      pigmentosum].
AB  - Natural leucocyte interferon (IF) upon injection to two patients affected with
      Xeroderma pigmentosum for three weeks stimulated the inhibited DNA replication
      and Host reactivation at the level of healthy donors. Tigasol--the drug used
      traditionally for the treatment of diseases caused by Xeroderma pigmentosum
      proved less effective than IF.

PMID- 7508410
TI  - [Children's health status in ecologically unfavorable regions].
AB  - Comparison of the official and research data on congenital developmental defects
      frequency (CDDF) in children of Novomoskovsk showed their disagreement. The
      average CDDF in these children is not more than the Middle European level.
      Physical development of children is insufficient for their biological age in 25%
      of cases. Many children suffer from respiratory diseases because of ambient air
      pollution. The majority of children (88-93%) are referred to 2-4 th health groups
      according to WHO classification.

PMID- 7508411
TI  - Correlations between clinical activity, endoscopic severity, and biological
      parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre
      study of 121 cases. The Groupe d'Etudes Therapeutiques des Affections
      Inflammatoires Digestives.
AB  - The relationships between clinical activity, endoscopic severity, and biological
      parameters in Crohn's disease have not been thoroughly investigated and a link
      was therefore sought between these three elements. The following parameters were
      determined simultaneously in 121 consecutive patients with colonic or ileocolonic
      Crohn's disease: Crohn's disease activity index, Crohn's disease endoscopic index
      of severity, and serum albumin, alpha 2-globulin, alpha 1-antitrypsin,
      orosomucoid, C reactive protein, erythrocyte sedimentation rate, platelets,
      lymphocyte and polymorphonuclear cell counts, haematocrit, and faecal alpha 1
      antitrypsin concentration. The distribution of these parameters was studied and
      transformation was used so that data matched the normal distribution closely. A
      weak but significant correlation (r = 0.32; p < 0.001) was found between clinical
      and endoscopic indices in the whole group of patients and this correlation seemed
      to be homogenous in various patient subgroups (clinically quiescent or active
      disease, pure colonic disease, untreated patients). Endoscopic or clinical
      indices were also found to be weakly linked with biological parameters (r <
      0.50). Stepwise linear regression identified C reactive protein as predictive of
      the clinical index, and, successively, alpha 2-globulin, erythrocyte
      sedimentation rate, faecal alpha 1-antitrypsin, serum orosomucoid, and alpha 1
      antitrypsin as predictive of the endoscopic index. Both predictions were poor-
      the biological variables accounting for only 22 and 44% respectively of the
      clinical and endoscopic index variations. In conclusion, Crohn's disease clinical
      activity seems to be virtually independent of the severity of the mucosal lesions
      and biological activity.

PMID- 7508412
TI  - Influence of neoadjuvant polychemotherapy on natural killer cell activity in
      patients with locally advanced cervical squamous carcinoma.
AB  - Peripheral blood natural killer (NK) cell activity against K562 tumor line was
      monitored in 16 patients with locally advanced squamous cervical carcinoma (II
      and III FIGO stages) during neoadjuvant polychemotherapy (cisplatin at 80 mg/m2
      and bleomycin at 30 mg/m2). There was a significant progressive decrease in NK
      activity during the three cycles of antiblastic treatment (P = 0.008) without
      significant depletion of NK cell (CD56 and CD16 monoclonal antibody positive cell
      percentage and absolute number). A significant relationship was shown between
      basal NK activity levels and response to polychemotherapy; in fact, nonresponder
      patients had a significantly lower mean value of NK activity before
      polychemotherapy than responders (P = 0.044). In conclusion, NK activity declines
      as a result of antiblastic therapy; although polychemotherapy reduces tumor
      spread, its antineoplastic action may be affected by this decreased immune
      reactivity.

PMID- 7508413
TI  - Genomic organization and localization of the gene encoding human preprogalanin.
AB  - An approximately 35-kb region of genomic DNA encoding the human preprogalanin
      gene including 5' and 3' flanking sequences has been cloned and characterized.
      Exons and flanking introns were sequenced to determine the structural
      organization of the gene. The gene spans 6.5 kb, with the first exon encoding
      only the 5' untranslated sequence. The coding region of preprogalanin and the 3'
      untranslated sequence is divided into five exons. Using high-resolution
      fluorescence in situ hybridization, the position of the single human
      preprogalanin gene was localized to chromosome 11q13.3-q13.5. Several oncogenes
      have been mapped to this region, which is also the breakpoint for the
      translocation t(11;14)(q13;q32) in chronic lymphocytic leukemia and diffuse B
      cell lymphoma.

PMID- 7508414
TI  - Detection of 98.5% of the mutations in 200 Belgian cystic fibrosis alleles by
      reverse dot-blot and sequencing of the complete coding region and exon/intron
      junctions of the CFTR gene.
AB  - We have previously shown that about 85% of the mutations in 194 Belgian cystic
      fibrosis alleles could be detected by a reverse dot-blot assay. In the present
      study, 50 Belgian chromosomes were analyzed for mutations in the cystic fibrosis
      transmembrane conductance regulator gene by means of direct solid phase automatic
      sequencing of PCR products of individual exons. Twenty-six disease mutations and
      14 polymorphisms were found. Twelve of these mutations and 3 polymorphisms were
      not described before. With the exception of one mutant allele carrying two
      mutations, these mutations were the only mutations found in the complete coding
      region and their exon/intron boundaries. The total sensitivity of mutant CF
      alleles that could be identified was 98.5%. Given the heterogeneity of these
      mutations, most of them very rare, CFTR mutation screening still remains rather
      complex in our population, and population screening, whether desirable or not,
      does not appear to be technically feasible with the methods currently available.

PMID- 7508415
TI  - Linkage mapping of the Aldo-2, Pax-5, Ambp, and D4h9S3E loci on mouse chromosome
      4 in the region of homology with human chromosome 9.
AB  - The genes for aldolase-B (ALDOB), the alpha 1-microglobulin/bikunin precursor
      (AMBP), the paired box gene PAX5, and the anonymous DNA marker D9S3 map to human
      chromosome 9 (HSA9). We have set out to map the mouse homologues of each of these
      genes. The mouse genes for Pax-5 and Ambp previously have been shown to map to
      MMU4. We have used an interspecific backcross to confirm these localizations and
      to map the mouse homologues of ALDOB (Aldo-2) and D9S3 (D4H9S3E) to the same
      chromosome. These genes were mapped with respect to the four anchor loci for
      MMU4. In addition, the panel of backcross DNAs had previously been typed for
      delta-amino levulinate dehydratase (Lv), orosomucoid-1 (Orm-1), and hexabrachion
      (Hxb), the human homologues of which map to HSA9q. The recombination distances +/
      the standard error between each pair of loci are D4Nds4-1.6 +/- 1.1-D4H9S3E-4.0
      +/- 1.7-Galt-0.8 +/- 0.8-Pax-5-4.8 +/- 1.9-Aldo-2-6.3 +/- 2.2-(Lv, Orm-1, Ambp)
      1.6 +/- 1.1-Hxb-4.0 +/- 1.7-Tyrp-1-4.8 +/- 1.9-Ifa. The data from this study have
      extended the known region of conserved synteny between human chromosome 9 and
      mouse chromosome 4.

PMID- 7508416
TI  - Immune-stimulating complexes as adjuvants for inducing local and systemic
      immunity after oral immunization with protein antigens.
AB  - Orally active synthetic vaccines containing purified antigens would have many
      benefits for immunizing against systemic and mucosal diseases. However, several
      factors have limited the development of such vaccines, including the poor
      immunogenicity of purified proteins and their usual ability to induce tolerance
      when given orally. Here, we show that incorporation of ovalbumin (OVA) into
      immune-stimulating complexes (ISCOMS) containing saponin prevents the induction
      of oral tolerance in mice. In parallel, the spleen and mesenteric lymph node of
      mice fed OVA ISCOMS are primed for class I major histocompatibility complex (MHC)
      restricted cytotoxic T-cell activity which recognizes physiologically processed
      epitopes on OVA. Oral immunization with OVA ISCOMS also stimulates high secretory
      IgA antibody responses in the intestine itself, as well as serum IgG antibodies.
      None of these active immune responses are detectable in mice fed OVA alone.
      Despite the potent priming of mucosal priming by OVA ISCOMS, re-exposure to
      antigen does not induce the intestinal immunopathology found in other systems
      after the breakdown of oral tolerance. Thus, ISCOMS have several unique
      properties as vectors for oral immunization and could provide a basis for future
      mucosal vaccines.

PMID- 7508417
TI  - Liposome-entrapped T-cell peptide provides help for a co-entrapped B-cell peptide
      to overcome genetic restriction in mice and induce immunological memory.
AB  - We have investigated the possibility of a T-cell epitope peptide providing help
      for a B-cell epitope peptide when both peptides are co-entrapped in the same
      liposomes. Epitope models used were a 28 amino acid peptide from the S region of
      the hepatitis B surface antigen (HBsAg) (subtype adw) containing an H-2s Th-cell
      epitope, and a 33 amino acid peptide from the pre-S1 region of the HBsAg (subtype
      adw) designed to exclude an adjacent H-2s T-cell epitope, the latter (pre-S1)
      peptide being recognized by SJL (H-2s) mice as a B-cell epitope. SJL(H-2s) mice
      were immunized twice intramuscularly with S or pre-S1 peptide alone, co-entrapped
      in the same liposomes or entrapped in separate liposomes which were mixed before
      injection. Analysis of sera for anti-peptide IgG1 antibodies revealed that the Th
      cell peptide provided help for the pre-S1 peptide only when the two peptides were
      co-entrapped in the same vesicles. This helper effect was found to correlate with
      the ability of S peptide (co-entrapped with the pre-S1) to stimulate T-cell
      proliferation in vitro. There was no IgG1 response against pre-S1 peptide in mice
      immunized with a mixture of the free peptides or a mixture of separately
      entrapped peptides. A helper effect, albeit much weaker, was also observed in
      mice immunized with the two peptides emulsified in incomplete Freund's adjuvant.
      Antisera from mice immunized with both peptides co-entrapped in liposomes were
      found to bind to full length (pre-S1 containing) recombinant HBsAg. Moreover,
      binding values were much higher than those seen with antisera from animals
      immunized with the liposomal S peptide above, presumably because of full access
      of anti-pre-S1 antibodies to the pre-S1 region of the rHBsAg. It is concluded
      that liposomes could serve not only as an immunological adjuvant for peptides but
      also as a carrier for Th- and B-cell epitopes thus eliminating the need for
      covalent linkage to a carrier protein.

PMID- 7508418
TI  - Murine malaria: anti-erythrocytic antibodies recognize N-acetyl neuraminic acid
      residues.
AB  - A cell-ELISA was developed using monolayers of glutaraldehyde-fixed normal as
      well as Plasmodium berghei-infected mouse erythrocytes for quantification and
      characterization of anti-erythrocytic autoantibodies in murine malaria. Testing
      normal (NMS) and peak parasitaemic sera (PPS) on erythrocyte monolayers treated
      with trypsin, sodium meta periodate, neuraminidase or heat, and competitive
      inhibition of antibodies with soluble sialic acid, revealed that some anti
      erythrocytic antibodies (which increase during the parasitaemic phase of
      infection) recognize N-acetyl neuraminic acid (NANA) residues on host
      erythrocytes. High levels of antibodies to NANA covalently conjugated to bovine
      serum albumin (BSA) were detectable in PPS. Such antibodies could be
      significantly absorbed out by preincubation of PPS with mouse erythrocytes
      (MRBC). Antibodies in PPS, when affinity-purified on a column of Fetuin-Agarose,
      were found to be reactive to normal as well as parasitized erythrocyte
      monolayers. Immunoglobulin isotyping and IgG subgroup typing revealed that most
      of the anti-erythrocytic autoantibodies in NMS were IgM and IgA, while in PPS
      there was an appreciable increase in IgG2a and IgG3. Affinity-purified anti-NANA
      antibodies reacted with DNA when tested in an ELISA. There was a significant
      positive correlation between anti-erythrocytic antibody and DNA-binding levels in
      NMS as well as PPS. The DNA-binding antibodies in PPS could be effectively
      absorbed out by preincubation of sera with fresh MRBC. Affinity determination of
      anti-erythrocytic antibodies eluted from MRBC revealed binding characteristics in
      the following order: MRBC > single-stranded DNA > double-stranded DNA.

PMID- 7508419
TI  - Tissue distribution of the non-polymorphic major histocompatibility complex class
      I-like molecule, CD1d.
AB  - The CD1 gene family is composed of five distinct molecules: CD1a, b, c, d and e.
      CD1a, b and c are primarily expressed thymically with limited extrathymic
      expression. Preliminary studies have shown that CD1d is primarily expressed
      extrathymically in gastrointestinal epithelial cells, renal tubular epithelial
      cells and B cells. This report characterizes the expression of CD1d in a variety
      of human tissues by immunohistochemistry using two anti-human CD1d monoclonal
      antibodies (mAb). CD1d was found in a wide range of tissues including the
      intestine, liver, pancreas, skin, kidney, uterus, conjunctiva, epididymis, thymus
      and tonsil. Within those tissues CD1d was mainly present in epithelial cells,
      vascular smooth muscle cells and parenchymal cells. Therefore, the tissue
      distribution of CD1d is distinct from CD1a-c and classical major
      histocompatibility complex (MHC) proteins implicating a unique role for CD1d in
      the immune system.

PMID- 7508420
TI  - Inhibition by chloroquine of the class II major histocompatibility complex
      restricted presentation of endogenous antigens varies according to the cellular
      origin of the antigen-presenting cells, the nature of the T-cell epitope, and the
      responding T cell.
AB  - Chloroquine treatment of antigen-presenting cells (APC) was explored as a tool to
      investigate the processing pathway for major histocompatibility complex (MHC)
      class II-restricted presentation of the endogenous secreted hen egg lysozyme
      (HEL) and transmembrane measles virus haemagglutinin (HA). A 72-hr pretreatment
      of the APC with 25 microM chloroquine blocked the presentation of the HEL(52-61)
      T-cell epitope generated from endogenous HEL to the I-Ak-restricted 3A9 T-cell
      hybridoma by MHC class II-transfected L cells expressing the invariant chain
      (Ii). The presentation of exogenously added HEL peptides was not affected. Under
      the same conditions, no inhibition of the presentation of HEL(106-116) to the I
      Ed-restricted G28 high-avidity T-cell hybridoma, nor of HA when synthesized by L
      cells, was observed. When B-lymphoid APC were used, inhibition was observed in
      every case with a low number of B APC pretreated for 48 hr with chloroquine prior
      to the T-cell stimulation test. Moreover, addition of chloroquine to untreated B
      APC during the T-cell stimulation assay was sufficient to inhibit completely the
      presentation of HEL(106-116) to the B10.D24.42 low avidity T-cell hybridoma.
      Altogether these studies suggest that an apparent resistance of endogenous Ag
      presentation to chloroquine inhibition may not necessarily indicate the existence
      of a non-endosomal pathway but may be due to the nature of the T-cell epitope, to
      the use of 'non-professional' APC such as L cells, to the use of T cells of high
      avidity, and to high amounts of pre-existing MHC class II-peptide complexes
      expressed by the APC. We demonstrate here that, at least in conventional APC such
      as B cells, class II-restricted presentation of both endogenous secreted HEL and
      transmembrane HA involves an endosomal pathway.

PMID- 7508421
TI  - Ontogeny of leucocyte populations in the spleen of fetal lambs with emphasis on
      the early prominence of B cells.
AB  - The presence and distribution of B cells and other early leucocyte populations
      are described in the spleen of fetal lambs from 40 to 134 days of gestation
      (length of gestation 150 days). Computer-assisted morphometric analysis and flow
      cytometry were used to quantify the early predominance of B cells in mid
      gestation. B cells appeared at about 48 days and increased in number to occupy
      over 20% of the spleen area at 77 days. All spleens were collected on their
      respective livers and at no stage did the livers contain more than a few IgM
      positive (+) cells, which were usually close to blood vessels. Two-colour flow
      cytometry demonstrated that only 1-2% of IgM+ cells expressed CD5 at 81 days.
      Beyond 77 days, with the expanding presence of T cells, the percentage of area
      occupied by IgM+ cells declined to stabilize at about 7% during late gestation.
      The conventional organization of the splenic white pulp was observed from 90 days
      along with 5' nucleotidase-positive primary follicles. Double staining technique
      using immunohistochemical methods demonstrated that IgM+ cells were proliferating
      in the spleen from as early as 51 days and that clusters of proliferating IgM+
      cells were prominent between 60 and 77 days. The results of the present study
      suggest that during the ontogeny of fetal lambs the spleen is a site of B-cell
      development or expansion before colonization of the ileal Peyer's patch and the
      subsequent generation of the preimmune antibody repertoire.

PMID- 7508423
TI  - Human tissue kallikrein induces hypotension in transgenic mice.
AB  - We investigated the role of the kallikrein-kinin system in blood pressure control
      by developing transgenic mice overexpressing human tissue kallikrein. Two lines
      of transgenic mice carrying the human tissue kallikrein gene under the control of
      the mouse metallothionein metal-responsive promoter were established. Human
      tissue kallikrein was identified in pancreas, salivary gland, kidney, liver, and
      spleen of the transgenic mice by a specific radioimmunoassay for human tissue
      kallikrein. The immunoreactive human tissue kallikrein reached high levels in the
      circulation. The linear displacement curves for the transgenic product were
      parallel with the human tissue kallikrein standard curve, indicating their
      immunologic identity. The expression of human tissue kallikrein transcript in the
      transgenic mice was further confirmed by Northern blot analysis and by reverse
      transcription-polymerase chain reaction followed by Southern blot. Both lines of
      transgenic mice had significantly lowered blood pressure (86.4 +/- 13.5 mm Hg
      [mean +/- SD], n = 8 and 78.9 +/- 12.4 mm Hg, n = 8) compared with control mice
      (100.9 +/- 5.0 mm Hg, n = 8). Induction with zinc did not lower the blood
      pressure further despite elevated expression of the transgene. Administration of
      aprotinin, a potent tissue kallikrein inhibitor, restored the blood pressure of
      the transgenic mice but had no significant effect on control littermates. Our
      findings raise the possibility of tissue kallikrein being a powerful modulator of
      blood pressure and provide a new animal model for the study of blood pressure
      regulation.

PMID- 7508424
TI  - Synthesis of a potent antagonist of substance P by replacing the CH2SCH3 and the
      alpha-carboxamide groups of the methionine at [Orn6]-SP6-11 by benzyl ester
      groups.
AB  - Analogues of [Orn6]-SP6-11 have been synthesized in which the CH2SCH3 group of
      Met11 is replaced by a COOCH3 or a COOBzl group. These analogues, which were
      tested for agonist and antagonist activity in three in vitro preparations
      representative of NK-1, NK-2 and NK-3 receptor types, were full agonists at NK-1
      receptors, showed very weak agonist activity at NK-2, receptors and were weak
      antagonists at NK-3 receptors. The above analogues were modified by substituting
      the alpha-carboxamide of residue 11 by a COOCH3 and a COOBzl group, respectively.
      The resulting analogues were found to be devoid of agonist activity in each of
      the functional assays. However, they showed weak antagonist activity at each
      receptor subtype, with the exception of the dibenzyl analogue, which was a potent
      and selective NK-1 receptor antagonist. It is concluded that appropriate
      modification of the side chain of Met11 and its alpha-carboxamide leads to a
      potent and selective at NK-1 receptor antagonist.

PMID- 7508422
TI  - Studies of the structure and binding properties of hamster female protein.
AB  - We report here the characterization of hamster female protein (FP), a member of
      the pentraxin family of plasma proteins, as a molecule composed of glycosylated
      subunits of 25,655 MW containing a single intrachain disulphide bridge. In the
      presence of EDTA the subunits are non-covalently associated as pentamers of mass
      approximately 128,000 MW, and in the presence of calcium they aggregate further,
      probably to form decamers. This pentamer-decamer transition at physiological
      ionic strength has not been described in other pentraxins. As previously
      reported, FP shares the capacity of C-reactive protein (CRP) in other species to
      bind phosphocholine and we show here that it also resembles human CRP in binding
      only weakly to agarose, to human AA amyloid fibrils in vitro, and to mouse AA
      amyloid deposits in vivo. It thus differs markedly from human and mouse serum
      amyloid P component (SAP) but it is nevertheless deposited in hamster AA amyloid
      in vivo and clearly is the hamster counterpart of SAP in other species. These
      results illustrate the subtle diversity among members of the otherwise conserved
      pentraxin family of vertebrate plasma proteins.

PMID- 7508425
TI  - A note on symbolism: a brief communication.

PMID- 7508426
TI  - Two potentially angiostatic factors, a steroid and L-azetidine-2-carboxylic acid,
      antagonize one another.
AB  - The proline analogue L-azetidine-2-carboxylic acid (LACA) systemically suppressed
      mast-cell-mediated angiogenesis, as measured by the rat mesenteric-window method.
      Dexamethasone and methylprednisolone at very low and non-toxic s.c. doses also
      somewhat inhibited the angiogenesis. Most interestingly, the co-administration of
      either of these steroids with LACA paradoxically stimulated angiogenesis. These
      findings suggest that in the future search for candidates for clinically-useful
      systemic angiostatic remedies, one may have to focus not only on the effect of
      individual drugs or agents, but also on the effect of such putative anti
      angiogenic agents when co-administered. The fact that two potentially angiostatic
      agents can antagonize one another has not previously been reported.

PMID- 7508427
TI  - Purchasing palliative care: availability and cost implications.
AB  - This paper reports on a survey of the availability of palliative care in
      Scotland, in the context of the internal market introduced as part of the NHS
      reforms. It is based on a survey of both the cost and availability of such
      service, with a discussion of the implications of this information for purchasers
      of palliative care.

PMID- 7508429
TI  - Chronic chlorpyrifos toxicosis in a cat.

PMID- 7508428
TI  - Use of Phaseolus vulgaris leukoagglutinating lectin in histochemical and blotting
      techniques: a comparison of digoxigenin- and biotin-labelled lectins.
AB  - An increase in the number of beta 1,6 branches of the trimannosyl core of
      asparagine-linked oligosaccharides has been shown to be directly correlated with
      the metastatic potential of cultured tumour cells. The Phaseolus vulgaris
      leukoagglutinating lectin (PHA-L) binds to beta 1,6 branches of tri- and tetra
      antennary oligosaccharides. We have applied digoxigenin- and biotin-conjugated
      PHA-L to establish a non-radioactive detection system for beta 1,6 branches,
      which can be used in lectin blotting as well as light and electron microscopic
      cytochemistry. For this purpose the HCT116 human colon carcinoma cell line and
      colon carcinoma tissue were investigated. Digoxigenin-conjugated PHA-L in
      conjunction with alkaline phosphatase-conjugated anti-digoxigenin antibodies was
      superior to biotin-conjugated PHA-L in lectin blotting with respect to
      sensitivity and specificity. Similarly, the digoxigenin conjugated PHA-L in
      conjunction with gold-labelled anti-digoxigenin antibodies resulted in more
      intense specific staining and lower background compared to biotin-conjugated PHA
      L visualized with a streptavidin immunogold complex. The specificity of lectin
      binding in blotting and cytochemical studies was demonstrated by the absence of
      staining when the lectin was omitted or preabsorbed with glycoprotein, and
      following pretreatment of the cellular homogenates or tissue sections by N
      glycosidase F. Our results demonstrate that digoxigenin-conjugated PHA-L provides
      high sensitivity and specificity for histochemical and blotting techniques and is
      amenable for quantification. The technique should have applications in tumour
      research.

PMID- 7508431
TI  - The treatment of pain in children with cancer.

PMID- 7508430
TI  - Cell-free hemoglobin potentiates acetylcholine-induced coronary vasoconstriction
      in rabbit hearts.
AB  - Cell-free hemoglobin (Hb) preparations have been shown to alter vascular tone in
      vitro and in vivo. The high affinity of Hb for nitric oxide, the putative
      endothelium-derived relaxing factor (EDRF), may be primarily responsible for this
      activity, but the contribution of tissue-damaging oxygen-derived free radicals
      has not been established. We investigated the effects of human Hb
      interdimerically cross-linked with bis-(3,5-dibromosalicyl)fumarate (alpha alpha
      Hb) on the coronary vasomotor response to acetylcholine (ACh) in isolated
      perfused rabbit hearts. Infusion of 0.1 g/dl alpha alpha Hb altered the dose
      dependent response to ACh, decreasing the calculated IC50 (ACh concn at which
      coronary pressure is 50% of its maximal value) from 3.96 +/- 0.34 to 0.85 +/-
      0.06 microM (P < 0.01). This augmented sensitivity to ACh was only partially
      reversed upon washout of alpha alpha Hb (IC50 1.93 +/- 0.13 microM). Simultaneous
      infusion of 60 microM deferoxamine mesylate with alpha alpha Hb attenuated this
      response (IC50 decreased from 3.86 +/- 0.27 to 1.73 +/- 0.38 microM), which was
      completely reversed after removal of alpha alpha Hb (IC50 3.41 +/- 0.17 microM).
      NG-nitro-L-arginine methyl ester (50 microM) and cross-linked cyanomethemoglobin
      (CNmet alpha alpha Hb, 0.1 g/dl) induced a significant (P < 0.05) increase in ACh
      induced vasoconstriction accompanied by a reduction in myocardial functions in
      the same range as that caused by alpha alpha Hb. Infusion of deferoxamine
      mesylate (60 microM) with CNmet alpha alpha Hb completely prevented the reduction
      in IC50 elicited by the infusion of CNmet alpha alpha Hb alone. These data
      demonstrate that alpha alpha Hb can alter coronary vasomotor responsiveness and
      suggest the involvement of at least two mechanisms, one that is related to an
      accessible ferrous heme and is reversible and another that does not require an
      open heme site and is irreversible.

PMID- 7508432
TI  - Pancreatic ascites.
AB  - Pancreatic ascites is rarely considered in the differential diagnosis of
      exudative ascites, and is in fact missed in a majority of patients. Eleven cases
      of pancreatic ascites are described. 63.6% were chronic alcoholics. The clinical
      diagnosis was cirrhosis of liver (5/11), tuberculous peritonitis (5/11) or
      malignant peritonitis (1/11). In all patients ascites was exudative and the
      ascitic fluid amylase was markedly elevated (mean +/- SD: 7815 +/- 6507 SU/dl).
      Endoscopic retrograde pancreatography (ERP) performed in 4 patients demonstrated
      the site of leak in 3. Laparoscopy performed in 8 patients helped in the
      diagnosis of pancreatic ascites in all, which was confirmed on histology.
      Laparoscopy ruled out other causes of exudative ascites in all. We conclude that
      pancreatic ascites should be suspected in any patient with exudative ascites,
      especially chronic alcoholics and that ascitic fluid amylase should be routinely
      performed in all such cases. High ascitic fluid content is virtually diagnostic
      of pancreatic ascites. ERP is essential in preoperative assessment or planning
      endoscopic treatment. Laparoscopy is an invaluable investigation to rule out
      other conditions such as tuberculous or malignant peritonitis and cirrhosis of
      liver.

PMID- 7508433
TI  - Porins and specific diffusion channels in bacterial outer membranes.

PMID- 7508434
TI  - Subunit composition of the high conductance calcium-activated potassium channel
      from smooth muscle, a representative of the mSlo and slowpoke family of potassium
      channels.
AB  - High conductance Ca(2+)-activated K+ (maxi-K) channels from bovine tracheal and
      aortic smooth muscle membranes have been purified employing monoiodotyrosine
      charybdotoxin binding as a marker for the channel and conventional
      chromatographic techniques. This K+ channel is composed of two subunits, alpha
      and beta, of 62 and 31 kDa, respectively. After sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, the electroeluted tracheal smooth muscle
      alpha-subunit was subjected to tryptic cleavage and a number of fragments were
      isolated by microbore C18 high performance liquid chromatography. Several of
      these peptides were microsequenced using Edman degradation techniques. Amino acid
      sequence information obtained from these fragments reveals the existence of very
      high sequence homology with the recently cloned mSlo maxi-K channel (Butler, A.,
      Tsunoda, S., McCobb, D. P., Wei, A., and Salkoff, L. (1993) Science 261, 221
      224). A specific anti-peptide antibody directed against the amino acid sequence
      of one of the fragments of the alpha-subunit is capable of specifically
      immunoprecipitating not only the denatured 125I-Bolton-Hunter-labeled alpha
      subunit, but also, under nondenaturing conditions, the complex of alpha and beta
      subunits, demonstrating specific noncovalent association of both subunits. Thus,
      our results indicate that the alpha-subunit of the purified tracheal smooth
      muscle maxi-K channel is a member of the mSlo family of K+ channels and forms a
      noncovalent complex with a beta-subunit. It is concluded that the extensive
      biochemical information acquired to date on smooth muscle charybdotoxin receptors
      is pertinent to the structure of native maxi-K channels.

PMID- 7508435
TI  - Specificity of priming reaction of HIV-1 reverse transcriptase, 2'-OH or 3'-OH.
AB  - It has not been unambiguously demonstrated whether the priming reaction of human
      immunodeficiency virus, type 1 (HIV-1) cDNA synthesis initiates with either the
      2'-OH or 3'-OH group of the 3'-terminal adenosine residue of tRNA(Lys-3). In this
      report, we synthesized tRNA(Lys-3) of which the 3'-terminal adenosine residue
      lacks either a 2'-OH or 3'-OH. These tRNA molecules were used for the HIV-1 cDNA
      priming reaction in a cell-free system consisting of a 141-base RNA template and
      purified HIV-1 reverse transcriptase. It was found that under the conditions
      used, the tRNA containing the 2'-deoxyadenosine was able to initiate the cDNA
      synthesis, while the tRNA with the 3'-deoxyadenosine was not. The results show
      that retroviral reverse transcriptase specifically primes cDNA synthesis from the
      3'-OH group. This is in contrast to bacterial reverse transcriptase, which
      initiates cDNA synthesis from the 2'-OH group of an internal guanosine residue of
      a template RNA.

PMID- 7508436
TI  - Hepatic cobalamin deficiency induced by hydroxycobalamin[c-lactam] treatment in
      rats is associated with decreased mitochondrial mRNA contents and accumulation of
      polycistronic mitochondrial RNAs.
AB  - Treatment of rats with hydroxycobalamin[c-lactam] (HCCL), a cobalamin antagonist,
      results in both increased hepatic mitochondrial content and the development of
      defects in mitochondrial ubiquinol:cytochrome c oxidoreductase and cytochrome c
      oxidase. The present study was designed to evaluate changes in hepatic
      mitochondrial RNA contents in response to HCCL treatment in rats. After 2 weeks
      of HCCL treatment, hepatic contents of the mature mitochondrial mRNAs (expressed
      normalized to 28 S rRNA) encoding subunit II of cytochrome c oxidase (CO II),
      subunit 1 of NADH dehydrogenase (ND1), and cytochrome b were reduced to values 40
      60% of those observed in RNA from control liver tissue. In addition, HCCL induced
      a pronounced accumulation of high molecular weight RNA species which hybridized
      to mitochondrial probes and represented polycistronic RNA sequences. The
      polycistronic RNAs were products of the heavy strand of the mitochondrial genome,
      and major species demonstrated hybridization patterns consistent with
      identifications corresponding to the 12-16 S rRNA, 12-16 S-ND1, 16 S-ND1, and CO
      II-ATP synthase subunit 6 regions of the mitochondrial genome. Maximal expression
      of the polycistronic mitochondrial RNA was observed after 2 weeks of HCCL
      treatment. Thus, HCCL treatment interferes with mitochondrial RNA processing and
      decreases the content of mature mitochondrial mRNAs. Altered expression of the
      mitochondrial genome may be responsible for the decreased electron transport
      chain activity known to result from HCCL administration.

PMID- 7508437
TI  - Competitive binding of vascular cell adhesion molecule-1 and the HepII/IIICS
      domain of fibronectin to the integrin alpha 4 beta 1.
AB  - The integrin receptor alpha 4 beta 1 binds to two different ligands, the
      extracellular matrix glycoprotein fibronectin and the endothelial cell surface
      protein vascular cell adhesion molecule-1 (VCAM-1). Using probes derived from
      each ligand and a variety of cell adhesion and ligand-receptor binding assays, we
      have investigated the relationship between the mechanisms of fibronectin and VCAM
      1 interaction with alpha 4 beta 1. CS1 peptide, which represents the dominant
      active site from the HepII/IIICS recognition domain in fibronectin, was found to
      inhibit VCAM-1-dependent adhesion in three different assays: MOLT-4 T
      lymphoblastic leukaemia cell attachment to immobilized recombinant soluble VCAM-1
      (rsVCAM-1), MOLT-4 cell attachment to monolayers of VCAM-1-transfected COS-1
      cells, and A375-SM melanoma cell spreading on immobilized rs VCAM-1. Half-maximal
      inhibition required CS1 concentrations of 1.7-3.0 mg/ml, some 3-7-fold higher
      than that needed to autoinhibit adhesion to CS1-IgG conjugate. Using a more
      sensitive solid-phase receptor-ligand binding assay, CS1 was found to be a potent
      inhibitor of the binding of rsVCAM-1 to alpha 4 beta 1 (half-maximal inhibition
      at 13 micrograms/ml). In agreement with cell-based assays, severalfold lower
      concentrations of CS1 were required to inhibit binding of recombinant HepII/IIICS
      region of fibronectin (half-maximal inhibition at 3 micrograms/ml). VCAM-1-alpha
      4 beta 1 binding was blocked not only by CS1 peptide but also by the recombinant
      HepII/IIICS region of fibronectin. Kinetic analysis of CS1 inhibition of VCAM-1
      binding revealed that it was directly competitive in nature, indicating that VCAM
      1 and fibronectin recognize either identical or spatially overlapping binding
      sites on alpha 4 beta 1. The implications of these results for the future design
      of VCAM-1 antagonists are discussed.

PMID- 7508439
TI  - Effect of a thiobenzimidazolone derivative on DNA strand transfer catalyzed by
      HIV-1 reverse transcriptase.
AB  - Thiobenzimidazolone (TIBO) derivatives are known inhibitors of the DNA polymerase
      activity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase
      (RT). The effect of a TIBO derivative ((+)-S-4,5,6,7-tetrahydro-9-chloro-5-
      methyl-6-(3-methyl-2-butenyl)-imidazol[4,5,1-jk]1,4-benzodiazapine -2-thione ) on
      the DNA strand transfer reaction catalyzed by HIV-1 RT (which is a function of
      both the DNA polymerase and RNase H activities) was investigated by delineating
      the effect of the drug on the constitutive DNA polymerase and RNase H activities)
      was investigated by delineating the effect of the drug on the constitutive DNA
      polymerase and RNase H activities. Single nucleotide incorporation on template
      primer 1 was used to study the DNA polymerase activity of HIV-1 RT while template
      primer 2 was used to study the effect of TIBO on the RNase H activity (polymerase
      independent). The drug was found to decrease the amplitude of the presteady-state
      burst when preequilibrated with the enzyme-substrate complex besides decreasing
      the steady-state rate of single nucleotide incorporations. In the absence of
      preincubation, TIBO did not affect the burst amplitude but decreased the steady
      state rate after the pre-transient phase. This suggested that binding of TIBO to
      RT was affected by the presence of template-primer and required dissociation of
      the enzyme from the template-primer for effective binding. The polymerase
      independent RNase H activity was activated in the presence of TIBO. The effect of
      TIBO on the overall process of DNA strand transfer is a balance between its
      inhibition of the polymerase activity and its activation of the RNase H activity.

PMID- 7508438
TI  - Sulfatides trigger increase of cytosolic free calcium and enhanced expression of
      tumor necrosis factor-alpha and interleukin-8 mRNA in human neutrophils. Evidence
      for a role of L-selectin as a signaling molecule.
AB  - Sulfatides have been established recently as ligands for L-selectin, and we
      investigated whether they trigger transmembrane signals through ligation of L
      selectin. We found that sulfatides trigger the increase of cytosolic free calcium
      in neutrophils and that this effect was strictly dependent on sulfation of the
      galactose ring, as non-sulfated galactocerebrosides were not stimulatory.
      Chymotrypsin and phorbol 12-myristate 13-acetate treatment of neutrophils caused
      shedding of L-selectin, but not of class I major histocompatibility complex
      antigens or beta 2 integrins, and blunted the capability of neutrophils to
      respond to sulfatides with an increase of cytosolic free calcium. Four different
      anti-L-selectin antibodies (DREG-200, LAM1/3, LAM1/6, and LAM1/10), but not four
      control antibodies directed against different surface molecules of neutrophils,
      also triggered an increase of cytosolic free calcium. The anti-L-selectin
      antibodies were stimulatory both if used in a soluble form, after cross-linking
      with anti-mouse F(ab')2 fragments, and immobilized to protein A of Staphylococcus
      aureus through the Fc fragment. With immobilized antibodies, an increase of
      cytosolic free calcium was found also by plating neutrophils on antibodies bound
      to protein A-coated coverslips and monitoring the increase of cytosolic free
      calcium by fluorescence microscopy. Both sulfatides and anti-L-selectin antibody
      effects were not inhibited by pertussis toxin, thus indicating that a pertussis
      toxin-sensitive GTP-binding protein was not involved in signal transduction.
      Sulfatides also triggered an increase of tumor necrosis factor-alpha and
      interleukin-8 mRNAs in neutrophils. Also to act as stimuli of cytokine mRNA
      expression, sulfatides required sulfation of the galactose ring, as non-sulfated
      galactocerebrosides were not stimulatory, and depended on expression of L
      selectin, as shedding of this molecules induced by chymotrypsin blunted their
      effects. These findings suggest that L-selectin can transduce signals activating
      selective cell function.

PMID- 7508440
TI  - Mapping the membrane topology of the closed state of the colicin E1 channel.
AB  - The membrane-associated closed channel state of the colicin E1 thermolytic
      peptide was studied by the Parallax Method of depth-dependent fluorescence
      quenching. A number of single Trp-containing peptides of colicin E1 were prepared
      to facilitate the use of Trp as a probe for the topography of the channel peptide
      in the membrane-bound state. The bound form of the channel peptide was studied by
      binding channel peptide to 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphatidylcholine/1-pal-mitoyl -2-oleoyl-sn- glycero-3-phosphatidylglycerol
      large unilamellar vesicles (60:40, mol/mol, approximately 0.1 microns diameter
      vesicles prepared by an extrusion technique) at low pH (pH 3.5). Depth-dependent
      fluorescence quenching studies using two nitroxide-labeled phospho-lipids (1
      palmitoyl-2-(5-doxylstearoyl)-sn-glycero-3-phosphatidylcho++ +-line and 1
      palmitoyl-2-(12-doxylstearoyl)-sn-glycero-3-phosphatidylcholine) were conducted
      to determine the membrane location of each Trp residue for the vesicle-bound
      peptide. The three naturally occurring Trp residues in the colicin channel
      peptide, Trp-424, Trp-460, and Trp-495, were found to reside at membrane depths
      (from the C-2 carbon of the fatty acyl chain) of 7.4, 3.1, and 8.4 A,
      respectively. Three Trp residues (Trp-355, Trp-460, and Trp-507) in the channel
      peptide were classified as shallow (0-5.0 A from C-2 carbon). The remaining 9 Trp
      residues were classified as moderately buried (5.1-10.0 A). None of the dozen
      tryptophyls were classified as deeply buried in the membrane bilayer (10.1-15.0
      A). A model for the colicin E1 channel based on these measurements along with
      previous data obtained from proteolysis, chemical labeling, ESR quenching, and
      mutagenesis experiments is proposed. This model for the closed state of the
      channel has as its central feature of the presence of only two trans-membrane
      segments. The membrane-associated portion of the channel includes the hydrophobic
      membrane anchor domain, Ala-474 to Ile-508. Furthermore, the fluorescence
      quenching data are consistent with the NH2-terminal helices (helices 1-7) lying
      on the surface of the membrane with the helical axis being oriented parallel to
      the membrane plane.

PMID- 7508442
TI  - Consensus repeat domains of E-selectin enhance ligand binding.
AB  - To study the structural characteristics of E-selectin necessary for mediating
      cell adhesion, we examined the role of the consensus repeat (CR) domains in E
      selectin function. Soluble constructs containing different numbers of CR domains
      were stably expressed in Chinese hamster ovary cells, purified to homogeneity,
      and characterized. The minimum functional unit of soluble E-selectin consisted of
      the lectin (Lec) and epidermal growth factor (EGF) domains alone (Lec-EGF) as
      indicated by its ability to mediate in vitro HL-60 cell adhesion. However, E
      selectin containing all six CR domains (Lec-EGF-CR6) at its COOH terminus was the
      most potent in blocking neutrophil or HL-60 cell adhesion to either immobilized E
      selectin or cytokine-stimulated human umbilical vein endothelial cells. This
      increased potency of Lec-EGF-CR6 in blocking cell adhesion was not due to CR
      mediated oligomerization of the protein. Lec-EGF-CR6 was most likely monomeric in
      solution, as judged by gel filtration fast protein liquid chromatography,
      membrane ultrafiltration, and chemical cross-linking analysis. Therefore,
      although the lectin and EGF domains are necessary and sufficient for mediating
      cell adhesion, the additional six CR domains, present in native E-selectin,
      contribute to the enhanced binding of E-selectin to its ligand.

PMID- 7508441
TI  - The 56K autoantigen is identical to human annexin XI.
AB  - Anti-56K autoantibodies are present in sera from patients with various autoimmune
      diseases, predominantly in sera from patients with rheumatoid arthritis, systemic
      lupus erythematosus, or Sjogren's syndrome. To clarify the molecular structure of
      this autoantigen, we isolated a 2.0-kilobase pair cDNA clone considered to encode
      the full-length 56K autoantigen. The longest open reading frame encodes a 505
      amino acid polypeptide, with a predicted molecular mass of 54.4 kDa. The in vitro
      translated protein is recognized by all anti-56K positive patient sera tested.
      Antibodies affinity-purified using the bacterially expressed recombinant protein
      recognized the 56K autoantigen in a HeLa cell extract. cDNA sequencing revealed
      that the 56K cDNA shares a high degree of homology in both nucleotide (87%) and
      amino acid sequence (92.5%) with bovine annexin XI, indicating that the 56K cDNA
      encodes the human homologue of annexin XI, a member of the Ca(2+)-dependent
      phospholipid binding protein family. Anti-56K autoantibody exhibits both a
      cytoplasmic and a nuclear staining in immunofluorescence experiments. Patients'
      sera recognize preferentially the N-terminal region of the protein, which is
      specific for 56K/annexin XI and not shared by other annexins, indicating that the
      autoimmune response to 56K/annexin XI in these patients is specific for this
      annexin family member.

PMID- 7508443
TI  - A single amino acid substitution flanking the fourth calcium binding domain of
      alpha IIb prevents maturation of the alpha IIb beta 3 integrin complex.
AB  - To define specific structural domains involved in the biosynthesis and processing
      of integrin subunits, we examined the biosynthesis of normal and mutated forms of
      the platelet-specific integrin alpha IIb beta 3. Platelet mRNA was isolated from
      a Glanzmann thrombasthenic patient who failed to express significant levels of
      the glycoprotein (GP) IIb-IIIa complex on the platelet surface. Sequence analysis
      of polymerase chain reaction-amplified platelet GPIIb mRNA revealed a Gly418-
      >Asp amino acid substitution in GPIIb. Gly418 is a highly conserved residue that
      flanks the fourth calcium binding domain of GPIIb. Cotransfection of Asp418 GPIIb
      and GPIIIa plasmid constructs into COS-7 cells resulted in the accumulation of a
      pre-GPIIb-IIIa complex that failed to reach the cell surface, in effect
      recreating the thrombasthenic phenotype. Pulse-chase and endoglycosidase studies
      demonstrated that the biosynthetic blockade occurred in a pre-Golgi compartment.
      Removal of the negatively charged carboxyl group of Asp418 GPIIb, creating Ala418
      GPIIb, rescued intracellular transport and surface expression of the integrin
      complex. Mutagenesis of a homologous Gly within the integrin alpha subunit alpha
      v also resulted in the failure to express alpha v beta 3 on the cell surface.
      These results suggest that the presence of a small, uncharged amino acid 6-8
      residues amino-terminal to the calcium coordination complex is crucial for the
      proper folding and maturation of integrin complexes.

PMID- 7508444
TI  - Structure of the gamma subunit of Escherichia coli F1 ATPase probed in trypsin
      digestion and biotin-avidin binding studies.
AB  - The arrangement and functional role of the gamma subunit of the Escherichia coli
      F1ATPase (ECF1) has been probed by protease digestion and avidin-biotin labeling
      experiments using wild-type enzyme and four mutants, gamma S8C, gamma T106C,
      gamma S179C, and gamma V286C, respectively. Trypsin was found to cleave the gamma
      subunit at four sites, Arg70, Lys199, Lys201, and Lys212. Cleavage at these four
      sites did not greatly reduce the high ATPase activity of the enzyme that is
      obtained when the epsilon subunit is removed by the protease treatment. However,
      prolonged trypsin cleavage led to loss of inhibition by epsilon subunit added
      back to the trypsin-treated enzyme. Endoproteinase-Lys-C cleaves the gamma
      subunit of ECF1 at three of the four sites, i.e. Lys199, Lys201, and Lys212, but
      not at Arg70. The enzyme was activated by treatment with this protease because of
      degradation and release of the epsilon subunit, but added pure epsilon subunit
      still caused inhibition of ATPase activity. Therefore, cleavage at Arg70 by
      trypsin is responsible for the loss of response to the epsilon subunit
      inhibition. Biotin was reacted with Cys residues at positions 8, 106, 179, and
      286 in different gamma subunit mutants and the accessibility of the biotin to
      avidin monitored in the intact ECF1 from the different mutants. Avidin was able
      to react with biotin when incorporated at position 106, not at 8, 179, or 286.
      The four trypsin cleavage sites, Arg70, Lys199, Lys201, and Lys212, as well as
      Thr106 are in regions of the gamma subunit predicted to be mainly beta-sheet and
      beta-turn structures.

PMID- 7508445
TI  - Signal transduction pathways from insulin receptors to Ras. Analysis by mutant
      insulin receptors.
AB  - We have examined the involvement of insulin receptor (IR) substrate-1 (IRS-1)
      and/or Shc in the upstream of Ras activation in insulin signaling using Chinese
      hamster ovary (CHO) cell lines overexpressing wild-type (CHO-IR) cells) or mutant
      insulin receptors. In CHO-IR cells, insulin rapidly phosphorylated IRS-1 and Shc
      at tyrosine residues and stimulated the formation of the active GTP-bound Ras
      (Ras.GTP). In contrast, a CHO cell line overexpressing the kinase-negative mutant
      insulin receptor substituting Arg1018 for Lys1018 was unable to tyrosine
      phosphorylate IRS-1 and Shc and failed to activate Ras in response to insulin. A
      CHO cell line overexpressing the mutant insulin receptor, substituting Ala960 for
      Tyr960 and which was known to exhibit impaired tyrosine phosphorylation of IRS-1
      and biological effects evoked by insulin, showed severely impaired insulin
      dependent tyrosine phosphorylation of Shc and moderately impaired activation of
      Ras. Another cell line overexpressing the mutant insulin receptor, lacking 82
      amino acids of the C terminus of beta-subunit and which was recently reported to
      retain normal insulin-dependent tyrosine phosphorylation of IRS-1, showed
      slightly impaired Ras activation at 10(-7) M insulin with severely reduced
      tyrosine phosphorylation of Shc protein. Furthermore, insulin did not induce the
      association of tyrosine-phosphorylated IRS-1 and Shc in CHO-IR cells. These
      results suggest that Shc and IRS-1 lie in the separate signaling pathways and
      that the tyrosine phosphorylation of IRS-1 with or without some low level of Shc
      phosphorylation may be enough to stimulate the submaximal accumulation of Ras.GTP
      complex and may need synergistically the higher level of tyrosine phosphorylation
      of Shc to induce the full activation of Ras in insulin signaling.

PMID- 7508447
TI  - Intermediates in translocation of diphtheria toxin across the plasma membrane.
AB  - Active diphtheria toxin consists of two parts, fragments A and B. Fragment A has
      enzymatic activity and inhibits protein synthesis. Fragment B binds to cellular
      receptors, and upon exposure to low pH it inserts into the membrane and
      facilitates translocation of the A fragment into the cytosol, concomitantly with
      formation of cation-selective channels. Reduction of the interfragment disulfide
      bridge is required for release of fragment A and intoxication. In cells treated
      with N-ethylmaleimide (NEM), which inhibits reduction of the disulfide bridge,
      fragment A was translocated to the cytosol but not released from fragment B. In
      the presence of NEM a peptide larger than fragment A was protected against
      extracellularly added Pronase. This peptide (M(r) approximately 24,000) was
      released to the supernatant fraction of saponin-treated cells. This indicates
      that fragment A, which is 21 kDa, is covalently attached via a disulfide bond to
      an N-terminal (M(r) approximately 3,000) piece of fragment B. The 24-kDa fragment
      disappeared upon reduction, and the 21-kDa fragment A appeared instead. NEM did
      not prevent channel activity by fragment B in the context of full-length toxin,
      demonstrating that channel formation occurs in spite of inhibited reduction of
      the disulfide bond. Thus, channel formation is not dependent on release of
      fragment A from the toxin-receptor complex.

PMID- 7508446
TI  - A beta turn in the cytoplasmic tail of the integrin alpha v subunit influences
      conformation and ligand binding of alpha v beta 3.
AB  - Integrins undergo conformational alterations in response to extracellular or
      intracellular stimuli, suggesting that structural elements within their exo- and
      cytoplasmic domains cooperate during transmembrane signaling. In this report, we
      identify a beta turn in the cytoplasmic tail of the alpha v subunit that impacts
      the ligand binding and conformation of the alpha v beta 3 heterodimer. Cells
      expressing a mutant alpha v beta 3 heterodimer composed of a truncated alpha v
      subunit, alpha v1000, lacking 18 carboxyl-terminal amino acids exhibits wild-type
      receptor structure and function. However, a truncation mutant, alpha v995,
      lacking five additional residues (PPQEE), which define a beta turn, is deficient
      in vitronectin and fibrinogen adhesion. This alteration in adhesive function is
      associated with two detectable structural changes in the alpha v beta 3
      heterodimer. First, the alpha v995 membrane-spanning light chain exhibits
      retarded electrophoretic mobility on SDS-polyacrylamide gels. Second, the alpha
      v995 beta 3 receptor shows an altered chymotryptic profile as measured by the
      loss of a 39-kDa proteolytic fragment from its ectodomain. These findings
      demonstrate that the ligand binding and structural properties of the intact alpha
      v beta 3 heterodimer can be influenced by a beta turn within the cytoplasmic tail
      of its alpha v subunit. The presence of homologous beta turns within other alpha
      subunit cytoplasmic tails suggests that this structural motif may play a role in
      regulating integrin-mediated bidirectional transmembrane signals.

PMID- 7508448
TI  - Oxidative dissociation of human alpha 2-macroglobulin tetramers into
      dysfunctional dimers.
AB  - Human alpha 2-macroglobulin is a broad-spectrum, homotetrameric antiproteinase
      that can maximally bind up to two proteinase molecules in a ternary complex.
      Proteinases cleave the inhibitor within a peptide stretch termed the bait region
      and induce the emergence of internal thiol esters whose nucleophilic scission
      precede a major conformational change which entraps enzymes within molecular
      cages. In a previous study, leukocyte-generated hypohalous acids and N-haloamines
      were identified as the first examples of physiologically relevant inactivators of
      the antiproteolytic activity of alpha 2-macroglobulin (Reddy, V. Y., Pizzo, S.
      V., and Weiss, S. J. (1989) J. Biol. Chem. 264, 13801-13809), but the mechanisms
      whereby the oxidants damaged the inhibitor remained undefined. We now demonstrate
      that N-chloramines (RNCl) destroy the antiproteolytic activity of alpha 2
      macroglobulin in an unusual biphasic process that results in the formation of
      inactive alpha 2-macroglobulin half-molecules. In the first phase, 8 eq of RNCl
      reacted with each alpha 2-macroglobulin subunit to generate a partially oxidized
      antiproteinase containing 8 methionyl sulfoxide residues/monomer. Structure
      function analyses demonstrated that the oxidized inhibitor retained its
      homotetrameric structure as well as its ability to entrap proteinases. In marked
      contrast, the oxidation of an additional 6 methionyl residues and a single
      tryptophanyl residue fractured the alpha 2 M homotetramer across its non-covalent
      axis into two pairs of disulfide-linked dimers. Despite the fact that the
      oxidized dimers displayed normal bait regions whose cleavage by proteinases
      initiated thiol ester scission, all antiproteolytic activity was lost.
      Furthermore, the oxidized dimers were unable to undergo the critical
      conformational changes normally associated with bait region cleavage or thiol
      ester scission. Together, these results demonstrate that chlorinated oxidants
      destroy the antiproteolytic activity of alpha 2-macroglobulin by attacking a
      subset of methionyl and tryptophanyl residues whose oxidation mediates the
      dissociation of the native homotetramer into conformationally locked dimers.

PMID- 7508449
TI  - Subcellular distribution of Ro ribonucleoprotein complexes and their
      constituents.
AB  - Ro ribonucleoprotein particles (Ro RNPs) are complexes of several proteins with a
      small RNA polymerase III-transcribed Ro RNA. Despite their relative abundance and
      evolutionary conservation no function has as yet been ascribed to these
      complexes. Also their subcellular distribution is still largely unknown as
      immunofluorescence studies concerning their localization have produced
      conflicting data. We have used cell enucleation to fractionate cells into
      cytoplasmic and nuclear fractions. Analysis of these fractions revealed an
      exclusively cytoplasmic localization for the Ro RNPs. The majority of the Ro RNAs
      are shown to be stably associated with all three known Ro RNP proteins. Although
      no Ro RNAs could be detected in the nuclear fraction, the Ro RNP-specific
      proteins were abundantly present. These nuclear non-Ro RNA-associated proteins
      are shown to be capable of binding Ro RNAs.

PMID- 7508450
TI  - Identification of a 102 kDa protein (cytocentrin) immunologically related to
      keratin 19, which is a cytoplasmically derived component of the mitotic spindle
      pole.
AB  - The mAb RK7, previously shown to recognize keratin 19, was also found to cross
      react with a biologically unrelated 102 kDa protein, which becomes associated
      with the poles of the mitotic apparatus. This newly identified protein, called
      cytocentrin, is a stable cellular component, may be at least in part
      phosphorylated, and displays a cell cycle-dependent cellular localization. In
      interphase cells, it is diffusely distributed in the cytosol and shows no
      affinity for cytoplasmic microtubules. It becomes localized to the centrosome in
      early prophase, prior to nuclear envelope breakdown, separation of replicated
      centrosomes, and nucleation of mitotic apparatus microtubules. During metaphase,
      cytocentrin is located predominately at the mitotic poles, often appearing as an
      aggregate of small globular sub-components; it also associates with some polar
      microtubules. In late anaphase/early telophase cytocentrin dissociates entirely
      from the mitotic apparatus and becomes temporarily localized with microtubules in
      the midbody, from which it disappears by late telophase. In taxol-treated cells
      cytocentrin was associated with the center of the miniasters but also showed
      affinity for some cytoplasmic microtubules. Studies employing G2-synchronized
      cells and nocodazole demonstrated that cytocentrin can become associated with
      mitotic centrosomes independently of tubulin polymerization and that microtubules
      regrow from antigen-containing foci. We interpret these results to suggest that
      cytocentrin is a cytoplasmic protein that becomes specifically activated or
      modified at the onset of mitosis so that it can affiliate with the mitotic poles
      where it may provide a link between the pericentriolar material and other
      components of the mitotic apparatus.

PMID- 7508451
TI  - Specific and sensitive high-performance liquid chromatographic method with
      fluorescence detection for measurement of lometrexol and its polyglutamates in
      biologic samples.
AB  - A reversed-phase high-performance liquid chromatographic (HPLC) assay is
      described for the quantitative determination of lometrexol in biological samples;
      the assay is rapid, simple, specific, and highly sensitive. The method requires
      the dissociation of lometrexol from folate-binding proteins present in blood and
      formation of a fluorescent oxidized derivative of the compound. The dissociation
      of lometrexol from folate-binding proteins was achieved by acidification to pH
      3.5 using ammonium formate, followed by serum protein precipitation with
      perchloric acid. The protein-free lometrexol was subsequently oxidized by MnO2 at
      90 degrees C for 10 min. Chromatographic separation of lometrexol without
      interference was achieved on a C18 reversed-phase column with a convex gradient,
      using acetonitrile-0.1% ammonium formate, pH 7.0, as the mobile phase. In human
      serum and urine the calibration curve was linear between 5 and 300 nM. The lower
      limit of quantification was 5 nM. The method has been applied successfully to
      measure serum and urinary levels of lometrexol in patients.

PMID- 7508452
TI  - Mycobacterium interjectum, a new species isolated from a patient with chronic
      lymphadenitis.
AB  - Mycobacterium-like organisms, isolates 2081/92 and 4185/92, were recovered from a
      lymph node of a child with chronic lymphadenitis. The growth characteristics,
      acid-fastness, and mycolic acids of the isolate were consistent with those for
      Mycobacterium species. The isolates were biochemically distinct from described
      Mycobacterium species, although they most closely resembled M. scrofulaceum.
      Comparative 16S rDNA sequencing showed that these isolates represent a new slow
      growing Mycobacterium species which is named M. interjectum. Our results
      demonstrate the importance of 16S rDNA sequencing for recognizing the diversity
      of species within the genus Mycobacterium.

PMID- 7508453
TI  - Detection of immunoglobulin M antibodies to glycoprotein G-2 by western blot
      (immunoblot) for diagnosis of initial herpes simplex virus type 2 genital
      infections.
AB  - Western blots (immunoblots) for the detection of immunoglobulin M (IgM)
      antibodies specific for herpes simplex virus type 1 (HSV-1) and HSV-2 in
      patients' sera were developed. The locations of the type-specific glycoprotein G
      (gpG-2) of HSV-2 (92- and 140-kDa forms) and glycoprotein C of HSV-1 (gpC-1),
      which carries mostly type-specific antigenic epitopes, were checked with specific
      monoclonal antibodies. Western blot assays for IgM antibody to gpC-1 or gpG-2
      were performed after depletion of IgG by precipitation with anti-human IgG. In
      patients with primary HSV-2 genital infections, seroconversion of IgM and IgG
      antibodies to both the 92- and 140-kDa forms of gpG-2 was observed, although both
      antibodies appeared in convalescent-phase serum after the first week. IgM and IgG
      antibodies to low-molecular-size polypeptides (40 to 65 kDa) were the first
      antibodies observed in patients with primary infection, but these antibodies were
      cross-reactive with HSV-1 and HSV-2. However, in patients with recurrent HSV-2
      infections, IgG antibodies to both forms of gpG-2 and the low-molecular-size
      polypeptides were found no matter how early after onset the patient was bled, and
      IgM to gpG-2 did not appear. In patients with nonprimary initial genital HSV-2
      infections, IgG antibody to HSV-1 was demonstrated in the first serum specimen,
      and HSV-2-specific IgM was found in 39% of the serum specimens. Hence, the
      Western blot assay can be used to test for IgM antibody to gpG-2, allowing for
      the retrospective diagnosis of inital HSV-2 infections and its use as a
      supplementary test to the gpG-2 IgG enzyme-linked immunosorbent assays developed
      elsewhere. In contrast, IgM antibody to gpG-2 is not usually detected in patients
      with recurrent HSV-2 infections.

PMID- 7508455
TI  - Differentiation of U.S. and European isolates of porcine reproductive and
      respiratory syndrome virus by monoclonal antibodies.
AB  - Monoclonal antibodies (MAbs) to two U.S. isolates of porcine reproductive and
      respiratory syndrome (PRRS) virus were prepared. Two MAbs specifically recognized
      a conserved epitope on the putative 15-kDa nucleocapsid protein of U.S. and
      European isolates of PRRS virus. Four other MAbs recognized epitopes on the 15
      kDa protein of U.S. but not European isolates of PRRS virus. Collectively, this
      indicates that PRRS viruses contain both conserved and divergent epitopes on the
      15-kDa viral protein.

PMID- 7508454
TI  - Escherichia coli in bacteremia: O-acetylated K1 strains appear to be more
      virulent than non-O-acetylated K1 strains.
AB  - A total of 174 blood isolates of Escherichia coli, collected during a 5-year
      period at the University Hospital Utrecht, were serotyped with rabbit sera
      against 171 O antigens and 73 capsule (K) antigens. The four most prevalent O
      antigen serotypes were O6 (n = 22), O18 (n = 19), O1 (n = 19), and O2 (n = 15).
      Thirty-one strains were not typeable with any of the O-antigen-typing sera. Of
      the 148 strains that were subjected to K-antigen serotyping, 34 strains lacked a
      K antigen and 41 were not typeable with the K-antigen-specific antisera used in
      the study. K1 was by far the most frequently found K-antigen serotype; this was
      followed by K2, K53, K5, K13, K7, K(A)28, and K15. Strains possessing a K1
      antigen were further classified as either O-acetyl-positive (n = 12) or O-acetyl
      negative (n = 21) strains. Retrospective analysis of patients infected with
      different E. coli isolates--nonencapsulated (n = 23), O-acetylated K1 (n = 12),
      and non-O-acetylated K1 (n = 21)--revealed clinical differences. More patients
      suffered from sepsis (94% versus 74%), and a higher rate of mortality was found
      in the group infected with K1 isolates (18 versus 9%) than in the group infected
      with nonencapsulated isolates. More patients with severe sepsis (25 versus 10%)
      and a higher mortality (33 versus 10%) were found in the group infected with O
      acetylated K1 isolates than in the group infected with non-O-acetylated isolated.
      Also, the hospitalization of these patients was prolonged. Thus, O-acetylated E.
      coli K1 strains seem to be more virulent than non-O-acetylated K1 strains.

PMID- 7508456
TI  - Identification of mycobacteria from animals by restriction enzyme analysis and
      direct DNA cycle sequencing of polymerase chain reaction-amplified 16S rRNA gene
      sequences.
AB  - Two methods, based on analysis of the polymerase chain reaction-amplified 16S
      rRNA gene by restriction enzyme analysis (REA) or direct cycle sequencing, were
      developed for rapid identification of mycobacteria isolated from animals and were
      compared to traditional phenotypic typing. BACTEC 7H12 cultures of the specimens
      were examined for "cording," and specific polymerase chain reaction amplification
      was performed to identify the presence of tubercle complex mycobacteria. Combined
      results of separate REAs with HhaI, MspI, MboI, and ThaI differentiated 12 of 15
      mycobacterial species tested. HhaI, MspI, and ThaI restriction enzyme profiles
      differentiated Actinobacillus species from mycobacterial species. Mycobacterium
      bovis could not be differentiated from M. bovis BCG or Mycobacterium
      tuberculosis. Similarly, Mycobacterium avium and Mycobacterium paratuberculosis
      could not be distinguished from each other by REA but were differentiated by
      cycle sequencing. Compared with traditional typing, both methods allowed rapid
      and more accurate identification of acid-fast organisms recovered from 21
      specimens of bovine and badger origin. Two groups of isolates were not typed
      definitively by either molecular method. One group of four isolates may
      constitute a new species phylogenetically very closely related to Mycobacterium
      simiae. The remaining unidentified isolates (three badger and one bovine) had
      identical restriction enzyme profiles and shared 100% nucleotide identify over
      the sequenced signature region. This nucleotide sequence most closely resembled
      the data base sequence of Mycobacterium senegalense.

PMID- 7508457
TI  - A new trichrome-blue stain for detection of microsporidial species in urine,
      stool, and nasopharyngeal specimens.
AB  - Detection of microsporidia in clinical specimens has relied on electron
      microscopy, histology, or staining. This article describes further alterations to
      the modified trichrome staining method which make it easier to identify
      microsporidial spores. The changes are a decrease in the phosphotungstic acid
      level and the substitution of a colorfast counterstain, aniline blue, for the
      fast green of the original stain. The modified stain provides good contrast
      between microsporidial spores and background material including human and fungal
      cells. Stool specimens from 139 human immunodeficiency virus-seropositive
      patients revealed that 5 patients were infected with Enterocytozoon bieneusi and
      6 patients had larger spores. Thin-section electron microscopy of the larger
      spores showed a structure consistent with that of either Encephalitozoon or
      Septata species. Three of the patients with Encephalitozoon- or Septata-like
      species had disseminated infection, with spores detected in nasopharyngeal
      aspirates and urine samples.

PMID- 7508458
TI  - Detection of Ehrlichia chaffeensis in human tissue by using a species-specific
      monoclonal antibody.
AB  - A mouse monoclonal antibody (MAb 1A9) was produced and used in detection of
      Ehrlichia chaffeensis in human tissues including kidney, liver, and lung by using
      an indirect immunohistologic stain. MAb 1A9 was specific to E. chaffeensis and
      did not react with other bacteria, including Ehrlichia canis, which is the
      organism most closely related to E. chaffeensis. It reacted with an epitope
      present in two surface proteins of E. chaffeensis with molecular masses of 29 and
      27 kDa. E. chaffeensis was easily detected in human tissue by immunohistology
      with MAb 1A9. This study demonstrates that our MAb can provide a specific and
      simple method for detection of E. chaffeensis in clinical specimens for
      establishing an etiologic diagnosis of human ehrlichiosis; it may also provide a
      tool for the investigation of immunopathologic characteristics in infected
      patients.

PMID- 7508459
TI  - Conservation of a protective surface antigen of Tritrichomonas foetus.
AB  - Bovine trichomoniasis is a sexually transmitted disease caused by the flagellated
      protozoan Tritrichomonas foetus. A protective surface antigen was previously
      identified and immunoaffinity purified from T. foetus isolate D1 with cross
      reactive monoclonal antibodies (MAbs) TF1.15 and TF1.17 (BonDurant, R. H., R. R.
      Corbeil, and L. B. Corbeil, Infect. Immun. 61:1385-1394, 1993). This antigen
      elicited antibody responses in the serum and cervicovaginal mucus of heifers.
      Thus, it may be useful as an immunodiagnostic reagent as well as a subunit
      vaccine. Conservation of the antigen in all strains would be crucial for either
      application. We investigated the conservation of this antigen among 36 isolates
      of T. foetus from Argentina, Costa Rica, and the United States using MAbs TF1.15
      and TF1.17 in an enzyme-linked immunosorbent assay. MAb TF1.17 reacted with 32 of
      the 36 isolates, whereas MAb TF1.15 reacted with all of the isolates tested. One
      of the isolates which did not react with MAb TF1.17 (i.e., D1#3) was investigated
      further by Western blotting (immunoblotting) to determine the reason for the lack
      of reactivity with one of the two cross-reactive MAbs. The antigenic band that
      was reactive with MAb TF1.15 had a molecular mass slightly lower than that of the
      corresponding band from isolate D1, which reacted with both MAbs TF1.15 and
      TF1.17. Thus, at least a major portion of the antigen appeared to be conserved.
      This was confirmed in a study of heifers infected with isolate D1#3. The vaginal
      immunoglobulin A antibodies of these infected heifers reacted with the antigen of
      isolate D1 that was immunoaffinity purified with MAb TF1.17. Therefore, even
      though the epitope recognized by MAb TF1.17 was missing in the challenge isolate
      (D1#3), the heifers developed an immune response to the rest of the molecule.
      These results indicate that the major portion of the previously described
      protective antigen is conserved in different isolates of T. foetus. This portion
      contains the epitope that reacts with MAb TF1.15. Most isolates express the whole
      antigen, which possesses both TFl.15 and TF1.17 epitopes, but the few isolates
      that are missing the portion containing the TF1.17 epitope may still elicit an
      immune reponse to the conserved portion. Thus, the protective surface antigen is
      promising for use in immunodiagnosis or vaccination against bovine
      trichomoniasis.

PMID- 7508460
TI  - Discrimination among thermophilic Campylobacter species by polymerase chain
      reaction amplification of 23S rRNA gene fragments.
AB  - By comparing nucleic acid sequences determined for one of the most variable areas
      of 23S rRNA genes of 23 Campylobacter strains, we were able to identify regions
      specific for thermophilic Campylobacter strains. Oligonucleotide primers
      corresponding to these unique regions were synthesized and used in the polymerase
      chain reaction. One primer pair selectively detected all thermophilic
      Campylobacter species, while four other primer pairs allowed discrimination among
      the thermophilic species Campylobacter coli, Campylobacter jejuni subsp. jejuni,
      Campylobacter lari, and Campylobacter upsaliensis. All primer sets were tested
      successfully on a large number of clinical isolates.

PMID- 7508461
TI  - Diagnostic value of recombinant Aspergillus fumigatus allergen I/a for skin
      testing and serology.
AB  - BACKGROUND: We report a clinical study comparing the recombinant Aspergillus
      fumigatus allergen I/a (rAsp f I/a) to two commercial A. fumigatus extracts in
      skin prick tests, intradermal tests, and serologic assays. METHODS: Patients with
      allergic bronchopulmonary aspergillosis and A. fumigatus-allergic patients with
      asthma, and control subjects, including allergic patients with asthma without
      allergy to A. fumigatus and healthy subjects, were investigated. RESULTS: All
      patients with allergic bronchopulmonary aspergillosis (n = 15) reacted to skin
      prick tests with the commercial extracts, and eight were sensitized to rAsp f
      I/a. Of 10 patients with well-characterized A. fumigatus-allergic asthma nine
      showed positive skin prick test results to at least one of the commercial
      extracts, and five reacted to rAsp f I/a. There was a strong correlation between
      skin test reactivity to rAsp f I/a and rAsp f I/a-specific serum IgE as
      determined by an antigen-specific ELISA. The healthy control subjects (n = 7) and
      allergic patients with asthma without A. fumigatus allergy (n = 6) did not react
      in skin prick and intradermal tests to rAsp f I/a, nor did they have detectable
      amounts of rAsp f I/a-specific IgE. In addition, patients with allergic
      bronchopulmonary aspergillosis showed significant elevated levels of rAsp f I/a
      specific IgG4 and IgG1 but no significant differences in rAsp f I/a-specific
      serum IgA levels when compared with the healthy control subjects. CONCLUSIONS:
      The data show that rAsp f I/a is a major allergen with biologic relevance in some
      A. fumigatus-allergic individuals as evaluated by skin prick tests, intradermal
      tests, or serologic methods. Furthermore, no discrepancies were observed between
      skin test results and rAsp f I/a-specific IgE. Hence the correlation between rAsp
      f I/a skin test results and serologic data indicates the potential of recombinant
      allergens for clinical applications and diagnosis of allergies.

PMID- 7508462
TI  - Fine specificity of B-cell epitopes on Felis domesticus allergen I (Fel d I):
      effect of reduction and alkylation or deglycosylation on Fel d I structure and
      antibody binding.
AB  - The repertoire of B-cell epitopes on the major cat allergen, Fel d I, was
      analyzed with monoclonal antibodies (MoAbs) in topographic mapping studies and in
      immunoassays with antigen derived from other cat (Felidae) species. Four
      essentially nonoverlapping epitopes on Fel d I, designated Fd1A to D, were
      defined by use of 15 anti Fel d I MoAbs in cross-inhibition radioimmunoassay.
      Only MoAbs directed against epitope Fd1B bound to putative Fel d I homologues in
      hair and dander extracts from seven other feline species (Panthera species, [n =
      5], Leptailurus serval, and Leopardus pardalus). Quantitative monosaccharide
      analysis showed that Fel d I was a glycoprotein, containing high levels of
      fucose, as well as glucosamine, galactose, and mannose. Binding of MoAbs and
      human IgG or IgE antibody to native, reduced and alkylated or deglycosylated Fel
      d I was compared by means of immunoprecipitation and immunoassay, and the effects
      of these treatments on the structure of Fel d I were analyzed by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis. On reduction and alkylation,
      Fel d I dissociated into 14 kd and 3.2 kd peptides, and deglycosylation with
      trifluoromethane sulfonic acid produced a 12 to 14 kd peptide. These procedures
      resulted in a 100- to 1000-fold loss in murine or human antibody binding activity
      and caused significant loss of secondary structure, as judged by circular
      dichroism spectroscopy. Treatment with potassium hydroxide also caused a marked
      loss in antigenic reactivity. In contrast, enzymatic deglycosylation generated a
      9 kd peptide, which showed strong reactivity with murine and human antibodies,
      comparable to native Fel d I. The results show that MoAbs define a broad
      repertoire of B-cell epitopes on Fel d I, one of which is expressed by other cat
      species. These epitopes are conformational and do not appear to involve
      oligosaccharide residues.

PMID- 7508463
TI  - IgE epitopes on the cat (Felis domesticus) major allergen Fel d I: a study with
      overlapping synthetic peptides.
AB  - BACKGROUND: The major cat allergen Fel d I is composed of two disulfide-linked
      polypeptide chains, chain 1 (70 amino acid residues) and chain 2 (92 amino acid
      residues). Reduction and alkylation of Fel d I eliminates almost all antigenic
      and allergenic activity, and detection of linear epitopes with synthetic peptides
      is therefore not expected. METHODS: We synthesized synthetic peptides of both
      chains of about 14 amino acid residues, overlapping by 7 residues. The peptides
      were coupled to Sepharose (Pharmacia, Uppsala, Sweden) and tested with sera of
      patients with cat allergy. RESULTS: Three peptides showed specific binding of
      human IgE, residues 25-38 and 46-59 of chain 1 and residue 15-28 of chain 2. IgE
      binding was inhibited by Fel d I and the corresponding peptide. Of 61 patients
      with cat allergy tested, 65% showed IgE binding to at least one of the peptides;
      46% showed IgE binding to peptide 25-38, 11% to peptide 46-59, and 28% to peptide
      15-28. Each peptide was recognized by only one of the 78 patients with negative
      RAST results. By affinity chromatography with peptide-Sepharose anti-Fel d I
      antibodies were isolated, also confirming the specificity of IgE binding to the
      peptides. The percentage of IgE antibodies against Fel d I reactive with the
      peptides varied with the serum and the peptide-Sepharose used and ranged from 2%
      to 55%. CONCLUSIONS: Because the affinity of IgE binding to the peptides was very
      low and only serum samples with high titers of Fel d I-specific IgE antibodies
      (RAST 4+/5+) showed significant binding, these peptides are not suitable for
      diagnostic purposes. However, the peptides are useful tools for comparing IgE and
      IgG responses and for studying the relationship to the T-cell epitopes on this
      molecule.

PMID- 7508464
TI  - Age-related macular degeneration: the current understanding of the status of
      clinicopathology, diagnosis and management.
AB  - BACKGROUND: This paper represents an up-to-date review of the current thoughts
      regarding the etiopathogenesis and management of the various varieties of age
      related macular degeneration (ARMD). METHODS: Included is a look at the
      epidemiology as well as the clinicopathologic basis for the development of the
      degenerative process. CONCLUSIONS: The clinicopathologic basis for development of
      ARMD is divided into drusen, lipofuscin development, solar radiation effects,
      photochemical damage and mediation by antioxidants, choroidal neovascularization,
      scarification, and retinal pigment epithelial detachment. The clinical
      presentation of both non-exudative and exudative ARMD is discussed with synopses
      of the mimickers of both outlined in the text. RESULTS: Current accepted methods
      of therapy are discussed including; laser intervention, surgical removal of
      membranes, and investigational modes of treatment including antioxidants.
      Specific management protocol is discussed based on the current knowledge base.

PMID- 7508465
TI  - Entrapment of dextran in plant cell capsules by reversible change of cell wall
      permeability.
AB  - Vesicular packing material (VP) made of clusters of extracted higher plant cells
      with the intact framework of their cell wall was used so far for permeation
      chromatography (vesicle chromatography). The objective of this study was to
      devise a method to entrap dextran in the vesicles. This can provide a means to
      entrap biocatalysts and secondly, to create aqueous two-phase systems with a
      stationary dextran phase for liquid-liquid partition chromatography. Dextran of
      molecular sizes above the separation limit of the plant cell wall cannot permeate
      into the intracellular space in aqueous medium. However, in hydrophilic organic
      solvent/water mixtures, dextran molecules can diffuse into the capsules. The
      removal of the organic solvent leaves the dextran trapped inside. There was an
      inverse correlation between the percentage of dextran permeating through the cell
      wall (Pperm) and the concentration of solvent required for dextran precipitation.
      The increase of permeability is therefore considered to be caused, to a great
      extent, by the decrease of the effective size of dextran molecules due to
      decreased solvation. Pperm was inversely correlated to the dielectric constants
      and the polarities of the solvents and, in the case of protic solvents, the
      hydrogen-bond acidities. No correlation was found to the hydrogen-bond
      basicities.

PMID- 7508466
TI  - [Colposcopic aspects of the cervix (cervical score CCL)].
AB  - TYPE OF STUDY: A retrospective study reviewing 481 colposcopic scores carried out
      on patients examined at CCL with a suspicion of dysplasia of the cervix, between
      January 1990 and September 1992. AIM: To evaluate the use and the reliability of
      a score designed to estimate the degree of severity of cases of cervical intra
      epithelial neoplasia (CIN). METHOD: Each method that describes the appearances of
      cervical pathology has been introduced in to a computerised programme. This
      places the score empirically limited to each parameter according to certain
      specific criteria worked out at CCL. RESULTS: The correlation of the CCL cervical
      score has been proven to be excellent because the sensitivity of this test is
      88.7% and contributes to the majority of controlled diagnoses. CONCLUSION: The
      principal value of a colposcopic score lies in the strictness with which the
      lesions are described and contributes to raising the quality of training of
      colposcopists and teaching this sub-specialty. Furthermore a systematic
      application of the analysis carried out makes it possible to take biopsies
      clearly directed and this is judged necessary. (CCL is the Centre of Colposcopy
      and Laparoscopy in the Department of Gynaecology and Obstetrics in the University
      of Lausanne.)

PMID- 7508467
TI  - [Oocyte donors. Psychological aspects].
AB  - This study concerns 63 oocyte donors who were investigated after a semi-directed
      interview. In our procedure all "personalized anonymity" donation took place on
      two levels: symbolic donation for close recipient, real donation for unknown
      recipient. All donors agree with anonymity without which some would not have
      preceded. Narcissic weakness often linked with recent trauma (death...) is often
      seen in patients who do not achieve the gift. Oblativity and happy motherhood are
      the most important reasons for oocyte gift.

PMID- 7508468
TI  - [Hodgkin's disease and pregnancy. 3 case reports and a review of the literature].
AB  - The association between Hodgkin's disease and pregnancy is rare. Hodgkin's
      disease does not affect the normal progress of the pregnancy nor of the fetus.
      Pre-therapy investigations of Hodgkin's disease have to be modified by pregnancy
      and in particular radiological examinations. Three are certain recommendations to
      be considered: termination of pregnancy is sometimes indicated in the first
      trimester but it does not have to be carried out routinely. Chemotherapy can be
      used in pregnancy as can radiotherapy if the disease is localised to the sub
      diaphragmatic area.

PMID- 7508469
TI  - Double epi-illumination microscopy with separate visualization of two antigens: a
      combination of epi-polarization for immunogold-silver staining and epi
      fluorescence for alkaline phosphatase staining.
AB  - We present a method for an epi-illumination immunohistochemical double staining
      approach. The method combines the use of an immuno-alkaline phosphatase technique
      and the immunogold-silver technique, visualized with epifluorescence and epi
      polarization illumination, respectively. Out of six tested alkaline phosphatase
      activity-revealing methods, only the reaction product obtained with the Becton
      Dickinson CAS Red kit showed an intense red fluorescence with a rhodamine filter
      set and no signal with epi-polarization illumination. The silver precipitate did
      not exhibit any signal with the rhodamine filter set. This allows separate
      observation and photographic recording of two antigens in one tissue section, an
      objective that cannot be achieved with conventional immunoenzyme double staining
      methods. The double epi-illumination approach presented is compatible with
      different immunoenzyme double staining protocols.

PMID- 7508470
TI  - Digital confocal microscopy allows measurement and three-dimensional multiple
      spectral reconstruction of Neisseria gonorrhoeae/epithelial cell interactions in
      the human fallopian tube organ culture model.
AB  - A strategy for measuring Neisseria gonorrhoeae attachment and invasion in the
      human Fallopian tube organ culture (FTOC) model via computerized image analysis
      (CIA) combined with "digital" confocal microscopy (DCM) was tested. DCM on serial
      image stacks of fluorescent latex beads reduced out-of-focus light propagation in
      the Z-axis (p < 0.005) and improved the shape factor of lateral three-dimensional
      reconstructions of the beads (p < 0.001). Sections of tissue infected for 44 hr
      with piliated, Opa+ gonococci were stained with fluorescein-labeled monoclonal
      anti-gonococcal antibodies, rhodamine-labeled phalloidin, and Hoechst 33342.
      Serial images collected at identical focal planes for each fluorochrome were
      subjected to DCM. Epithelial cytoplasmic regions of interest defined by rhodamine
      stained actin were superimposed on the corresponding fluorescein-stained and
      Hoechst-stained images. Fluorescent objects defined by gray-scale threshold were
      measured by computerized image analysis using different border treatments to
      differentiate attached from intracellular gonococci or count cell nuclei.
      Compared with raw images, measurement of DCM images was less dependent on
      threshold choice (p < 0.05). DCM augments conventional microscopy in removing out
      of-focus light from fluorescent images, in reconstructing three-dimensional
      images, and in quantitatively differentiating extracellular from intracellular
      gonococci in a natural target tissue.

PMID- 7508471
TI  - A combined ELISA-immunoelectron microscopic approach for topological mapping of
      membrane protein epitopes: application to the nicotinic acetylcholine receptor.
AB  - Identification of epitope localization on either side of the lipid membrane by
      immunoelectron microscopy constitutes an intrinsic powerful method of structure
      determination for membrane proteins. We have developed a method allowing
      measurement and observation, under almost identical experimental conditions, of
      the binding of monoclonal antibodies (MAb) to membrane-bound acetylcholine
      receptor from Torpedo marmorata electric tissue. This method, based on ELISA and
      electron microscopy of negatively stained specimens, was developed with MAb of
      known epitope specificity. With native membrane fragments, we found that MAb
      bound to extracellular epitopes in a stoichiometric manner, whereas almost no
      binding was detected for intracellular epitopes. The treatment based on tissue
      homogenization in the presence of Zn2+ ions and sucrose resulted in the formation
      of large, stable openings, rendering accessible about 25% of intracellular
      epitopes. Electron microscopic observations showed a clear distinction between
      antibody binding to either intracellular or extracellular epitopes, both with
      native and Zn(2+)-treated membranes. In addition, the binding of one antibody
      directed against an extracellular epitope was strikingly dependent on the packing
      density of acetylcholine receptor molecules, thus enabling us to further
      distinguish between two levels of accessibility for extracellular epitopes. The
      method presented here is of general application for studies of epitope mapping in
      membrane proteins.

PMID- 7508472
TI  - Golgi-Colonnier method: correlation of the degree of chromium reduction and pH
      change with quality of staining.
AB  - We examined the role of chromium reduction in the Golgi-Colonnier method,
      correlating the quality of neuronal impregnation with the levels of hexavalent
      (CrVI) and trivalent (CrIII) chromium in the tissue and in the chromation fluid
      (CF). The concentrations of both chromium species were assessed by measuring
      spectrophotometrically the CrVI before and after oxidizing the sample and by
      calculating the ratio of CrVI to total chromium (chromium ratio, CrR). The CrR
      was almost identical in the tissue and the CF, decreasing exponentially during
      chromation due to a progressive consumption of CrVI to form CrIII. Satisfactory
      cell impregnation was obtained only when the CrR was 0.45-0.7, regardless of
      other factors. The CrR values could be accurately predicted by the pH increase of
      the CF; this increase has proven to be a most reliable criterion to decide the
      endpoint of the chromation process. The dependence of cell staining on the
      [CrIII], together with the well-known ability of this species to bridge proteins,
      suggests that the key event for cell impregnation is the cross-linking of
      neuronal proteins by CrIII polymers.

PMID- 7508473
TI  - F(ab) secondary antibodies: a general method for double immunolabeling with
      primary antisera from the same species. Efficiency control by chemiluminescence.
AB  - We propose a general solution to the problem of using antibodies originating in
      the same species for double immunohistochemical labeling. It relies on the use of
      a two-step protocol in which a secondary polyclonal monovalent F(ab) antibody
      present in the first step blocks access in the second of the secondary antibody
      to the primary antibody, which is continuously present from the first step. The
      monovalence of the F(ab) fragment eliminates the possibility of its linking the
      primary antibody from the second step. We designed two efficiency tests to
      explore the limits of the method by the very sensitive chemiluminescent system
      applied to sections of human pituitary tissue. They confirmed both the validity
      of the method and the necessity of adapting working conditions to obtain a
      complete lack of interference.

PMID- 7508474
TI  - The amido black assay: a simple and quantitative multipurpose test of adhesion,
      proliferation, and cytotoxicity in microplate cultures of keratinocytes (HaCaT)
      and other cell types growing adherently or in suspension.
AB  - A new multipurpose cell micro-assay has been developed, using the protein dye
      amido black 10B as an indicator of cell numbers in 96-well plates. The assay is
      reliable, rapidly performed and can be combined with morphological evaluation and
      photography of stained cells. It permits investigations of various cell types
      including the human keratinocyte line HaCaT and subclones, mouse 3T3 fibroblasts
      and myeloma cells X63-Ag8.653. Briefly, cells are fixed by formaldehyde or
      glutaraldehyde and, following aspiration of fixative and non-adherent cells, are
      stained by amido black at pH 3.5. The protein-bound dye is completely eluted by
      NaOH and is scanned in a microplate reader at 620 nm against 405 nm or 750 nm.
      Non-adherent and semi-adherent cells are assayed by centrifugation of plates
      before fixation. The assay revealed a good linear correlation between absorbance
      of amido black, cell count and DNA content within the range 1000-64,000 HaCaT
      cells/well. The slope of the regression line varied with different cell types.
      Experiments with HaCaT cells and its c-Ha-ras oncogene-transfected subclones
      demonstrated the suitability of the assay for optimizing culture conditions, dose
      response studies and for the screening and quantification of cell adhesion to
      extracellular matrix molecules. The assay was also used to evaluate cytotoxicity
      of drugs such as hexadecylphosphocholine, target cell killing in co-cultures with
      interleukin-2-activated lymphocytes, and the testing of hybridoma antibodies for
      their biological effects on proliferation and adhesion. The assay is highly
      reproducible, sensitive, independent of cellular aggregation and economic for
      multiple applications.

PMID- 7508475
TI  - A novel in situ model to study Pneumocystis carinii adhesion to lung alveolar
      epithelial cells.
AB  - Pneumocystis carinii, an extracellular parasite thriving in the lungs of
      immunosuppressed mammals, is a major cause of death in AIDS patients in the USA.
      As a prelude to growth, the parasite adheres mostly to type I pneumocytes lining
      the alveolar spaces. The mechanism of adherence remains unknown, largely because
      of difficulties in isolating type I pneumocytes and maintaining them in vitro. As
      a first step to understand P. carinii adherence to its natural substrate, we
      developed an in situ method to directly study parasite binding to lung alveolar
      cells. We used formaldehyde-fixed paraffin-embedded sections of normal rat lung
      as substrate for adhesion. As in its binding to the lungs in vivo, P. carinii
      adhered preferentially to type I pneumocytes. Adherence was saturable, time and
      dose dependent, and selectively blocked by glycoconjugates, in particular bovine
      submaxillary mucin, fetuin, and asialofetuin, suggesting that it may be mediated
      by a lectin type of interaction. Further, IgG of rats with P. carinii pneumonia
      inhibited adherence, suggesting that it may react with parasite ligands involved
      in the recognition of type I cell receptors. Our results demonstrate the
      usefulness of the in situ model for studying the mechanisms of P. carinii
      adherence to alveolar cells. In addition, this method may be valuable for
      identifying neutralizing antibodies and drugs potentially useful for controlling
      the infection in vivo.

PMID- 7508476
TI  - Assay and purification of Fv fragments in fermenter cultures: design and
      evaluation of generic binding reagents.
AB  - Fv fragments whose genes have been cloned using common PCR primers carry
      identical peptide motifs at their termini. We have raised antibodies against the
      C-terminal motif of the VH chain GQGTTVTVSS and evaluated their utility as
      reagents for the assay and purification of Fvs in the fermenter culture. Three
      different Fvs were included in the investigation. We found that the motif was
      exposed and available for capture when Fv fragments were blotted onto
      nitrocellulose paper or adsorbed directly onto microtiter plates. In contrast,
      the motif was either partially or totally obscured when the Fv was complexed with
      immobilised antigen or when free in solution. This reactivity profile enabled us
      to develop a general-purpose assay for Fv protein, but not a general-purpose
      assay for monitoring active Fv. The apparent inaccessibility of the C-terminus of
      VH conflicts with currently held views on the three-dimensional structure of
      these molecules.

PMID- 7508477
TI  - Induction of low density and up-regulation of CD11b expression of neutrophils and
      eosinophils by dextran sedimentation and centrifugation.
AB  - Neutrophils and eosinophils circulating in an activated state are of low density.
      However, purification procedures such as dextran sedimentation and centrifugation
      may influence the density and function of cells. In the present study we have
      evaluated the effect of dextran sedimentation and subsequent centrifugation on
      the density and CD11b expression of neutrophils and eosinophils. Direct density
      separation of whole blood resulted in 17.7 +/- 9.0% low density neutrophils (<
      1.090 g/ml) and 8.7 +/- 3.5% low density eosinophils (< 1.093 g/ml). Dextran
      sedimentation at room temperature prior to density separation yielded 57.8 +/-
      14.7% low density neutrophils and 43.2 +/- 8.0% of low density eosinophils.
      Additional centrifugation after dextran sedimentation resulted in an increase of
      these numbers to 91.7 +/- 3.1 and 69.8 +/- 11.7% respectively. The density shifts
      were found with hypertonic as well as isotonic Percoll. Furthermore, it was shown
      that dextran sedimentation resulted in an increased CD11b expression on
      neutrophils as well as eosinophils. During subsequent washing by centrifugation,
      a further increase in CD11b expression was observed together with lactoferrin
      release. The effects of dextran sedimentation on density and CD11b expression
      were independent of extracellular calcium. These results indicate that dextran
      sedimentation induces the release of specific granule compartments with
      subsequent expression of CD11b, resulting in changes in granulocyte density.

PMID- 7508478
TI  - Measurement of bactericidal/permeability-increasing protein in human body fluids
      by sandwich ELISA.
AB  - A sensitive sandwich ELISA has been developed to measure levels of native
      bactericidal/permeability-increasing protein (BPI) as well as two recombinant
      forms of BPI (rBPI and rBPI23) in human body fluids. The linear range for the
      rBPI and rBPI23 standard curves were 100-6000 pg/ml and 25-800 pg/ml
      respectively. Recovery of different concentrations of rBPI spiked into pooled
      human plasma samples averaged 83% and ranged from 65% at 300 ng/ml to 97% at 3
      ng/ml. Recovery of rBPI23 averaged 56% and ranged from 30% at 0.5 ng/ml to 90% at
      50,000 ng/ml. Because LBP is present in normal human plasma and shares sequence
      homology with BPI, the effects of rLBP on the BPI ELISA were also evaluated.
      Under standard assay conditions, rLBP caused minimal interference with BPI
      detection. At 100 micrograms/ml, rLBP generated a signal equivalent to 3 ng/ml of
      rBPI and 0.6 ng/ml of rBPI23. Matched serum and plasma samples were collected
      from 20 healthy adults to measure endogenous levels of BPI. The range of BPI
      concentrations was < 0.2-2.1 ng/ml in plasma and 4.9-72.1 ng/ml in serum. Western
      blot analysis indicated that the BPI ELISA immunoreactivity in plasma and serum
      correlated with the presence of a protein doublet (M(r) approximately 60,000),
      which comigrated with native BPI extracted from human neutrophils. These data
      demonstrate that low levels of holo-BPI are present in plasma, and suggest that
      additional quantities of BPI were released from neutrophils during the process of
      coagulation.

PMID- 7508479
TI  - Two-stage selection of sequences from a random phage display library delineates
      both core residues and permitted structural range within an epitope.
AB  - Libraries of random peptides can be screened to identify species which interact
      with antibodies or receptors. Similarly, maps of native molecular interactions
      can frequently be deduced by screening a limited set of peptide fragments derived
      from sequences within a native antigen or ligand. However, the existence of cross
      reactive sequences that mimic original epitopes and the limited replaceability of
      amino acid residues suggest that the sequence space accessible by a receptor can
      be much broader. Definition of this space is of particular importance where
      structural information is required for peptidomimetic or drug design. We have
      used a two-stage selection scheme to expand the sequence space accessible by a
      phage display library and to define peptide epitopes of the anti-FLAG octapeptide
      monoclonal M2 antibody. Affinity selection of a primary library of 2 x 10(6)
      random decapeptides identified a non-contiguous core of three residues in the
      binding motif Tyr-Lys-Xaa-Xaa-Asp. A second stage library with 2 x 10(7)
      individual clones bearing the core motif but with the remaining flanking and
      internal residues re-randomized permitted access to a broader sequence space
      represented in a library equivalent to several orders of magnitude larger. Data
      here demonstrate that extended access to binding sequence space permitted by
      multi-stage screening of phage display libraries can reveal not only essential
      residues required for ligand binding, but also the ligand structural range
      permitted within the receptor binding pocket.

PMID- 7508480
TI  - Evaluation of different methods for the detection of outer membrane proteins and
      lipopolysaccharides of Pasteurella haemolytica by immunoblotting.
AB  - The optimal conditions for the detection of outer membrane proteins (OMPs) and
      lipopolysaccharide (LPS) of Pasteurella haemolytica by immunoblotting were
      evaluated. The variables examined included the equilibration time of the gels
      before transfer, composition of the transfer buffer, type of blotting membrane,
      blocking agent, effect of the zwitterionic detergent Empigen BB on protein
      renaturation, and the development reagent. The composition of the transfer buffer
      and time of gel equilibration significantly affected the efficiency of transfer
      of both OMPs and LPS. However, the optimal conditions for the transfer of OMPs
      were not the same as those for LPS. Thus, optimal transfer of OMPs occurred in
      Tris-glycine buffer, with prior equilibration of the gels to allow for expansion,
      whereas optimal transfer of LPS was achieved in Tris-glycine-methanol buffer with
      no equilibration of the gels. In Tris-glycine-methanol buffer, gel equilibration
      resulted in a significantly reduced transfer of both OMPs and LPS, probably due
      to the removal of SDS from these components. The use of Zeta-Probe blotting
      membrane which, unlike nitrocellulose, does not require methanol for optimal
      protein binding, did not result in improved binding of OMPs or LPS in the absence
      of methanol and, even after prolonged blocking (> 2 h), gave higher background
      staining than did nitrocellulose. Effective blocking of nitrocellulose was
      achieved with 3% (w/v) gelatin, 2.5% (w/v) skimmed milk or 0.3% (v/v) Tween 20,
      whereas increased background staining occurred with 1% (w/v) bovine serum albumin
      or 1% (w/v) ovalbumin. The incorporation of Empigen BB in the primary antibody
      buffer did not improve antibody recognition of proteins as a result of their
      renaturation. For the horseradish-peroxidase enzyme development system, the
      substrate 3,3'-diaminobenzidine tetrahydrochloride was more sensitive, and
      developed more quickly, than 4-chloro-1-naphthol, but faded more rapidly after
      drying of the membrane. 4-chloro-1-naphthol was more suitable for identifying
      OMPs because less background staining occurred, whereas 3,3'-diaminobenzidine
      tetrahydrochloride was more suitable for the detection of LPS due to its greater
      sensitivity.

PMID- 7508481
TI  - Dual staining of lymphocyte membrane antigens with colloidal gold and
      biotinylated horseradish peroxidase.
AB  - Double immunoenzymatic labelling procedures for the localization of antigens on
      cells in tissue sections using horseradish peroxidase (HRP) and alkaline
      phosphatase have been described previously, but mainly for detecting antigens on
      different cells. With this type of staining when two antigens are present on the
      same cell, an optimal colour combination that shows a high contrast between the
      basic colour of each enzyme substrate product is difficult to achieve and the
      interpretation of their mixed colour intermediate is subjective. We present a
      method for the simultaneous demonstration of two antigens on the same cell. The
      method can be used to label either single cells in suspension, or cells in
      paraffin fixed tissue, using a combination of a particulate label, colloidal
      immunogold-silver, and an enzymatic label HRP-DAB. The method is easy to perform
      and utilises commercially available staining kits.

PMID- 7508482
TI  - Flow cytometric measurement of non-specific esterase activity.
AB  - alpha-Naphthyl acetate esterase (alpha-NAE) is primarily found in mononuclear
      phagocytes and may be used to distinguish them from other leucocytes.
      Conventional cytochemical techniques are subjective and may be difficult to
      interpret, especially with cells which express only low levels of activity. This
      has caused difficulties in the classification of non-lymphoblastic leukaemias.
      This paper describes the adaptation of a cytochemical assay for use with the flow
      cytometer. The alpha-NAE activity of peripheral blood mononuclear cells was
      examined and found to be associated with the expression of the surface antigen
      CD14. The reaction could be inhibited by sodium fluoride. A series of human cell
      lines were also compared for alpha-NAE activity. Distinct differences in staining
      observed between the cell lines correlated with the number of cell-associated
      granules observed under the microscope.

PMID- 7508483
TI  - Use of Merocyanine 540 and Hoechst 33258 for the selective killing of
      contaminating mycoplasmas in cell cultures.
AB  - Mycoplasma infection can substantially affect the biological properties of cells
      in vitro. We have devised a method for the selective killing of mycoplasmas,
      e.g., A. laidlawii, M. fermentans, M. hyorhinis and M. arginini, from
      experimentally infected cell cultures. This approach is based on the differential
      binding of the lipophilic fluorescent probe Merocyanine 540 followed by
      illumination with visible light. The efficiency of the procedure depends on the
      Merocyanine 540 concentration, the intensity of illumination, and the presence of
      oxygen in the medium. When A. laidlawii contaminated corneal endothelial cell
      cultures were treated simultaneously with Merocyanine 540 and DNA-binding
      fluorochrome Hoechst 33258 and then illuminated, a significant degree of
      eradication was observed, even after one cycle of treatment. This combined
      treatment is therefore recommended as an effective method of purging mycoplasmas
      from contaminated cultures.

PMID- 7508484
TI  - Chronic granulomatous disease presenting in childhood with Pseudomonas cepacia
      septicaemia.
AB  - Two children who presented with fever, enlarged liver and spleen and ascites were
      found to have Pseudomonas cepacia septicaemia which proved fatal despite
      appropriate antibiotics and maximum supportive care. Chronic granulomatous
      disease of childhood (CGD) was subsequently diagnosed in both children. The
      possibility of CGD needs to be considered in any child with unexplained P.
      cepacia infection.

PMID- 7508485
TI  - [Meniscal transplantation with a synovial pedicle--an animal experiment].
AB  - The effect of a meniscal transplantation with a synovial pedicle in the avascular
      portion of the meniscus was investigated in an animal model. An inner (free edge
      side) half of the middle segment of the medial meniscus, about 6 mm in length, of
      an adult dog was resected, and a half thickness of the remaining outer
      (peripheral) meniscus was advanced with a synovial pedicle to fill in the
      resected portion and sutured with 6-0 interrupted Nylon sutures. As a control,
      the same procedure without the synovial pedicle was performed for comparison.
      Twenty-four dogs were treated with synovial pedicle and 13 without. The treated
      meniscus was excised every four weeks postoperatively up to 32 weeks for gross
      observation and histological examination. The histological findings at the
      junction between the advanced meniscus and the remaining meniscus in the group
      with the synovial pedicle were as follows: 1) At eight to 20 weeks, vascular
      proliferation and fibroblasts formation were present. 2) At 24 weeks, the
      vascularity decreased and the junction was filled with collagen fibers. 3) At 32
      weeks, the junction was almost completely repaired with chondrocytes. In
      contrast, in the group without the synovial pedicle, the junction was connected
      with fibrous tissue, but with no chondrocytes even at 32 weeks. This enhancement
      of the meniscus repair with the synovial pedicle was considered to be due to
      reparative ability of the synovial cells, neovascularization through the synovium
      and viability of the advanced meniscus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508486
TI  - Urinary epidermal growth factor is excreted from the rat isolated perfused kidney
      in the absence of plasma.
AB  - Large amounts of epidermal growth factor (EGF) are excreted in urine and the
      majority of this urinary EGF appears to be of renal origin. EGF is synthesized in
      the kidneys as a membrane-bound 160 kDa precursor, in the thick ascending limb of
      Henle and in the early part of the distal convoluted tubule. Very little is known
      about how EGF is released from cell membranes into urine but proteolytic cleavage
      of the membrane-bound EGF precursor seems likely. The purpose of this study was
      to examine whether plasma constituents are necessary for urinary excretion of
      EGF. In the rat isolated kidney perfused at a pressure of 90 mmHg with a modified
      Krebs-Henseleit buffer containing oncotic agents, the quantity of EGF excreted
      into the ureteral effluent was 67% of the amount excreted by the rat kidney in
      vivo. The EGF excreted by the isolated kidney behaved like urinary EGF upon gel
      filtration. Administration of the proteinase inhibitor aprotinin reduced urinary
      EGF excretion from the rat isolated perfused kidney by approximately 50%. In
      conclusion, the rat isolated perfused kidney excreted significant amounts of
      urinary EGF without having access to plasma, and EGF excretion was reduced by
      aprotinin. This is further evidence suggesting an intrarenal source of urinary
      EGF and suggests that the EGF precursor in the rat kidney is processed by
      enzyme(s) of renal origin.

PMID- 7508487
TI  - Effects of insulin-like growth factor-I and its analogues on bovine hydrogen
      peroxide release by neutrophils and blastogenesis by mononuclear cells.
AB  - The biological potencies of recombinant human insulin-like growth factor-I (IGF
      I) and two of its analogues were examined for hydrogen peroxide release by
      neutrophils and blastogenesis by mononuclear cells. The binding affinities of
      these peptides for bovine serum IGF-binding proteins (IGFBPs) and IGF-I receptors
      on bovine neutrophils and mononuclear cells were also investigated. Relative to
      control treatment containing no IGF-I, preincubation of neutrophils with 12.5
      micrograms/l of IGF-I, des(1-3)IGF-I (an analogue of human IGF-I lacking the N
      terminal tripeptide Gly-Pro-Glu) and long R3 IGF-I (an analogue of human IGF-I
      with arginine replacing glutamate at position 3 of human IGF-I and the N-terminal
      extension Met-Phe-Pro-Ala-Met-Pro-Leu-Ser-Ser-Leu-Phe-Val-Asn) increased the
      release of H2O2 by 65%, 64% and 32% respectively. However, the difference in
      stimulating the release of H2O2 between long R3 IGF-I and other two (IGF-I and
      des(1-3)IGF-I) was reduced at a dosage of 100 micrograms/l. In the absence or
      presence of 2.5% fetal calf serum (FCS), 100 micrograms/l of IGF-I, des(1-3)IGF-I
      but not long R3 IGF-I significantly stimulated thymidine incorporation into
      mononuclear cells. In addition, des(1-3)IGF-I was more potent than IGF-I in
      stimulating thymidine incorporation into mononuclear cells in the presence of
      2.5% FCS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508488
TI  - Sequential change of the hypervariable region of the hepatitis C virus genome in
      acute infection.
AB  - Hepatitis C virus (HCV) infection is characterized by persistence of liver
      inflammation that often leads to end-stage liver disease, although the mechanisms
      are not fully understood. A hypervariable region (HVR) has been reported in the
      E2/NS1 region of the HCV genome, in which striking diversity is found among
      different HCV isolates. To investigate the association of the HVR alterations
      with the clinical courses of HCV infection, a longitudinal analysis of the HVR in
      patients with acute HCV infection was carried out. Plasma samples were obtained
      at several times in three patients with acute hepatitis C. Plasma RNA was
      extracted and reverse transcribed, and DNA fragments that included the HVR were
      amplified by PCR. The sequences of the HVR were directly determined from the PCR
      products by the dideoxy chain termination method, from which amino acid sequences
      were deduced. In all cases, plasma HCV-RNA disappeared with the improvement of
      the initial alanine aminotransferase (ALT) elevation, but HCV-RNA reappeared
      about 1 year later with or without deterioration of the hepatitis. In a case of
      sporadic acute hepatitis, the HCV in the recurrent phase had seven amino acid
      substitutions in the HVR compared with that in the acute phase, although no amino
      acid changes were noted during the initial acute phase. In a case of
      posttransfusion hepatitis, a marked difference was observed between the acute and
      the recurrent phases, with an amino acid homology of 30% (8/27). The mutation
      rate of the HVR had a tendency to accelerate as the HCV infection progressed to
      the chronic stage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508489
TI  - Prevalence of antibody to hepatitis C virus (HCV) in HIV-1-infected patients
      (nice SEROCO cohort).
AB  - The prevalence of antibody to hepatitis C virus (HCV) in a cohort of 272 HIV
      infected patients was assessed by means of 4 anti-HCV assays: a 1st generation
      and a neutralization test, a 2nd generation test, and a confirmatory test, the
      dot-blot Matrix HCV immunoassay. The cohort included, as a single risk factor,
      35.7% intravenous drug users (IVDUs), 25% homosexual men, 30.1% heterosexual
      individuals, 5.9% transfused patients, 0.7% occupational infections, and 2.6%
      patients with unknown infection source, and was studied on entry and in samples
      collected for up to 36 months. Results showed that on entry (i) sera of 83 out of
      272 members of the cohort were positive by the HCV 1st generation EIA (30.5%); 70
      were confirmed by the neutralization test (84.3%); (ii) 115 of the cohort were
      reactive with the 2nd generation HCV EIA (41.3%); (iii) with the dot-blot
      immunoassay 99 (86.1%) of the cohort were confirmed and 16 remained
      indeterminate. The overall confirmed HCV antibody-positive rate in these 272
      patients was 36.4%. Antibody to HCV was detected in 78.3% of IVDUs, 18.3% of
      heterosexual individuals, 31.2% of transfused patients, and only 2.9% of
      homosexual men. The 36-month follow-up of this cohort revealed that 4/145
      patients became anti-HCV positive by second generation assay. Hepatitis B markers
      were frequently associated with HCV in IVDUs (71.1%) but infrequently in
      heterosexual (8.5%) or homosexual (1.5%) individuals. Our results suggest that
      HCV 2nd generation EIA used in combination with the semiautomated dot-blot assay
      as a confirmatory test improves the specificity and sensitivity for HCV antibody
      detection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508490
TI  - Virus-induced autoimmunity in hepatitis C virus infections: a rare event.
AB  - Serial serum samples from 16 Italian patients presenting with acute hepatitis C
      virus (HCV) infections (which progressed to chronic hepatitis in six) were
      screened for the non-organ-specific autoantibodies most frequently associated
      with autoimmune hepatitis (AIH), as well as for antibodies against the hepatic
      asialoglycoprotein receptor (ASGP-R) and against the GOR peptide. One patient had
      low titres (1:10-1:80) of liver-kidney microsomal (LKM-1) antibodies during the
      recovery phase and three others had transient low titres of anti-smooth muscle
      (IgM class, 1:10) or anti-ASGP-R (1:150-1:300). Anti-GOR was detected in 43 (65%)
      of 66 sera from 13 of these patients. There was no correlation between any of
      these findings and progression to chronicity. By comparison, 18 patients with AIH
      studied concurrently before institution of immunosuppressive therapy all had
      antinuclear and/or smooth muscle antibodies, or LKM-1, at 1:40-1:640 and anti
      ASGP-R at 1:300-1:2,100. None of these 18 had evidence of HCV infection and all
      were seronegative for anti-GOR. The findings indicate that the autoantibodies
      usually associated with AIH are rare in HCV infections but the virus can very
      occasionally induce a transient autoimmune response. Anti-GOR appears to be an
      antibody specifically related to HCV infection and is probably not a marker of
      induced autoimmunity, and it does not predict progression to chronic hepatitis.

PMID- 7508491
TI  - Immune recognition of linear antigenic regions within the hepatitis B pre-C and C
      gene translation products using synthetic peptides.
AB  - The antibody recognition of linear regions within the amino acid (aa) sequence of
      hepatitis B (HB) core antigen (HBcAg), e antigen (HBeAg), and pre-C region was
      investigated in 46 patients infected with hepatitis B virus (HBV), and one
      immunized rabbit. Peptide analogues were synthesized to cover the complete
      product of the C-gene, including the pre-C region using various synthetic
      methods. Two carriers of hepatitis B surface antigen (HBsAg) with anti-HBe,
      recognized pin-bound decapeptides covering amino acid (aa) 76-83 of HBc/eAg, and
      the most essential residues were found to be Asp78, Pro79, Arg82, and Asp83. Pre
      C peptides were recognized by IgG1 or IgG3 in sera from two out of ten cases with
      acute HB, in four out of twelve sera from HBeAg-positive carriers of HBsAg, and
      in two out of twelve sera from anti-HBe-positive carriers of HBsAg. Two sera from
      the cases of acute HB showed strong reactivity of the IgG3 isotype with HBc/eAg
      peptides 61-85. Five of the sera from HBeAg-positive carriers of HBsAg were
      weakly reactive with peptides 41-60, 61-85, 121-140, and/or 141-160. Eight of the
      sera from anti-HBe-positive carriers of HBsAg recognized aa 121-140 of HBc/e with
      IgG1, IgG3, and/or IgG4 isotypes. IgG from one immunized rabbit recognized
      peptides 1-20, 61-85, and 71-90, and the T-cells recognized peptides 1-20 and 71
      90. Thus, human and rabbit antibodies recognize linear antigenic regions within
      the pre-C, and within regions 1-20, 41-60, 61-85, 121-140, and 141-160 of
      HBcAg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508493
TI  - What don't you know about HIV?

PMID- 7508492
TI  - Intrafamilial transmission of hepatitis C virus: the important role of inapparent
      transmission.
AB  - To evaluate the intrafamilial transmission of hepatitis C virus (HCV) 104 index
      patients with type C chronic liver disease and their 307 family contacts were
      interviewed. After a questionnaire on the risk factors of parenteral exposure,
      blood samples were obtained and tested for liver biochemistry and anti-HCV
      antibody by enzyme-linked immunosorbent assay (Abbott II). Overall, 52 family
      contacts (17%) were positive for anti-HCV, indicating a higher anti-HCV
      prevalence among family contacts than among the general population in Taiwan. The
      anti-HCV prevalences in parents, spouses, children, and other contacts of the
      patients were 54% (14/26), 28% (25/91), 6.9% (10/143), and 6.4% (3/47),
      respectively. The contacts of index patients had increasingly greater risk of HCV
      infection when they became older and had lived longer with index patients. All
      family contacts were divided into two groups categorized by whether the index
      patients had or did not have a history of parenteral exposure. Among 126 family
      contacts of the 42 patients without parenteral exposure, blood transfusion and
      surgery were the factors significantly associated with HCV infection in these
      family contacts (odds ratio = 7.26, 95% confidence interval = 2.32-32.67; odds
      ratio = 3.95, 95% CI = 1.29-12.11, respectively). Risk factors were not
      significantly associated with HCV infection among 181 family contacts of the 62
      index patients with parenteral exposure. It is concluded that the index patients
      without parenteral exposure appeared to have acquired the disease from HCV
      infected family members with risk factors. Most of the index patients had a
      history of parenteral exposure and in turn served as the source of the disease
      for family members.

PMID- 7508494
TI  - Improving HIV/AIDS care through education.
AB  - It is essential that primary healthcare providers, including dentists, be able to
      screen and counsel their patients for AIDS and exposure to HIV. This article
      reviews efforts of the AIDS Education and Training Center for Southern California
      to train healthcare providers.

PMID- 7508495
TI  - The changing profile of the HIV/AIDS epidemic.
AB  - The HIV/AIDS epidemic has undergone significant changes in the population
      affected and the opportunistic infections most commonly seen since the disease
      was first identified. Dental care providers must be aware of the changing profile
      of this disease in order to provide adequate assessment and treatment of their
      patients, and appropriate referrals to other healthcare providers.

PMID- 7508496
TI  - Viral pathogenesis and opportunistic infections.
AB  - Knowledge about the pathogenesis and management of HIV infection has increased
      dramatically over the last decades. Because of advances in drugs, diagnosis and
      management, HIV-infected patients are living longer. This paper provides current
      concepts of HIV pathogenesis and antiviral therapy, and an overview of AIDS
      related opportunistic infections.

PMID- 7508497
TI  - Common oral lesions associated with HIV infection.
AB  - More than 40 different lesions involving head and neck areas have been associated
      with HIV infection. The oral cavity may manifest the first sign of HIV infection.
      Early detection of these conditions can lead to early diagnosis of HIV infection
      and subsequent appropriate management. Signs, symptoms and management of the most
      common HIV-associated oral lesions are discussed.

PMID- 7508498
TI  - The dentist, HIV and the law: duty to treat, need to understand.
AB  - An understanding of three areas of law--anti-discrimination, workplace safety and
      privacy and confidentiality--is helpful to dentists in meeting their
      responsibilities to treat HIV-infected individuals. This understanding also will
      assist in establishing a practice atmosphere in which HIV-infected patients will
      feel comfortable enough to fully disclose their condition and discuss treatment
      options with the care provider.

PMID- 7508499
TI  - Assaults on our image.

PMID- 7508500
TI  - Malignant benign neonatal sacrococcygeal teratoma.
AB  - Thirty-six patients with benign neonatal sacrococcygeal teratoma (SCT) were
      treated in our medical center from 1972 to 1990. Mean gestational age was 38.6 +/
      3.3 weeks with a mean birth weight of 3,484.0 +/- 938.5 g. Twenty-nine patients
      (89%) were females. The majority of the tumors (75%) contained cystic components
      and 96% were Altman classification I and II. The initial surgical removal of the
      SCT (including the coccyx) was carried out during the first 7 days of life. Six
      patients (22%) developed recurrence of the tumor. Three were benign and
      reappeared locally after 12 +/- 3 months and were reexcised. The mean serum alpha
      fetoprotein level in this group was 13 +/- 1 g/L. The malignant recurrence (all
      originally reported as being mature benign SCT) appeared at 20.3 +/- 1.5 months
      and had markedly elevated serum alpha-fetoprotein levels (7,320 +/- 4,630
      micrograms/L). All the patients in this group had multimodal therapy including
      complete excision of the recurrent tumor. We conclude that SCT, although
      histologically benign, has an alarming potential to recur either as a benign or
      malignant tumor during the first 2 years of life. Close follow-up for at least 3
      years (frequent examination, serum alpha-fetoprotein, and diagnostic imaging) is
      recommended for all patients who had undergone excision of SCT in the newborn
      period.

PMID- 7508501
TI  - Mediastinal teratomas: review of 15 pediatric cases.
AB  - One hundred fifty-three children with a teratoma presented to one hospital
      between 1970 and March 1992. The clinical and pathological features of 15
      patients with mediastinal teratomas are reviewed; six were newborn and nine aged
      from infancy to 13 years. Thirteen patients including the six newborns presented
      with respiratory distress and all 15 patients had a mass on chest radiograph. A
      definite diagnosis of teratoma was not made preoperatively in any of these
      patients. At operation, a median sternotomy was used to approach seven anterior
      tumors and a lateral thoracotomy performed in the other eight patients.
      Histologically two were mature, 10 had immature elements, and three were
      malignant teratomas. The patients with malignant tumors were all over 12 years of
      age and died within 6 months of treatment. All six neonates had immature
      teratomas. Raised serum alpha-fetoprotein levels provided useful markers in two
      patients with recurrent tumors. Three conclusions can be drawn: (1) mediastinal
      teratomas are rare in children and frequently are not diagnosed before operation;
      (2) in newborns these tumors may be immature and present with respiratory
      distress; and (3) a median sternotomy gives excellent exposure for anterior
      mediastinal tumors.

PMID- 7508502
TI  - Routine use of the nitric oxide stain in the differential diagnosis of
      Hirschsprung's disease.
AB  - Hirschsprung's disease (HD) is defined as a congenital absence of ganglion cells
      in the distal bowel. Functionally, there is a loss of enteric neuromuscular
      inhibition. Inhibitory intestinal innervation includes extrinsic nonadrenergic,
      noncholinergic (NANC) nerves. Nitric oxide (NO) is proposed to be a NANC
      neurotransmitter. Sites of NO synthesis can be localized using a NO-dependent
      nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical
      assay. We present a study of the distribution of NO neural elements in patients
      with HD. Routine hematoxylin-eosin (HE) histology as well as histochemical
      localization of NO synthase activity was carried out on fixed laminae and
      sectioned tissue of infant colon. NO synthase positive nerve cells and fibers
      were found throughout the wall of the proximal ganglionated colon. In the
      myenteric plexus disposition of these nerves parallels the known NANC
      innervation. "Aganglionic" distal colon displayed disrupted ganglia and increased
      nerve fibers. Selective preservation of NO synthesizing neurons was also seen.
      Punctate labeling of an apparent nonneuronal origin was also noted on the surface
      of arterioles. NO stain simplifies the pathological diagnosis of HD. The presence
      of NO positive nerve cells in HD suggests that aganglionosis is a misnomer. The
      lack of characteristic HE findings in other forms of neuronal intestinal
      dysplasia indicates the need for routine simple, more sensitive neural staining
      of colonic biopsies in selected infants with constipation.

PMID- 7508503
TI  - A voltage-dependent proton current in cultured human skeletal muscle myotubes.
AB  - 1. A voltage-dependent proton current, IH, was studied in cultured myotubes
      obtained from biopsies of human muscle, using whole-cell recording with the patch
      clamp technique. 2. With a pHo of 8.0 and a calculated pHi of 6.3, IH was
      activated at voltages more depolarized than -50 mV and its conductance reached
      its maximum value at voltages more depolarized than +10 mV. 3. Studies of the
      reversal potential of IH during substitution of K+, Na+, Ca2+, Cl-, Cs+ and H+ in
      the extracellular solution indicated that protons were the major charge carriers
      of IH. 4. IH was also activated during a voltage step to +22 mV with a pHo of 7.3
      and a calculated pHi of 7.3. 5. Acidification of the extracellular solution led
      to a shift towards depolarized voltages of the conductance-voltage relationship.
      6. Stationary noise analysis of IH suggested that the elementary event underlying
      IH was very small with a conductance of less than 0.09 pS. 7. Extracellular
      application of various divalent cations blocked IH. The block by divalent cations
      was voltage dependent, being more efficient at hyperpolarized than at depolarized
      voltages. For Cd2+, the Michaelis-Menten constant (Km) for the block was 0.6
      microM at -28 mV and 10.4 microM at +12 mV. 8. Ca2+ was a less efficient blocker
      than Cd2+ but could block IH at physiological concentrations (the Km values for
      the block were 0.9 mM at -38 mV and 7.3 mM at -8 mV). 9. The voltage-dependent
      properties of IH and its ability to be affected by pH and Ca2+ suggest that IH
      might be used by skeletal muscle cells to extrude protons during action
      potentials. 10. A model of IH activation suggests that under extreme conditions,
      the conductance of IH can reach 40% of its maximum value after less than ten
      action potentials.

PMID- 7508504
TI  - Expression of subunit-omitted mouse nicotinic acetylcholine receptors in Xenopus
      laevis oocytes.
AB  - 1. Nicotinic acetylcholine (ACh) receptors in developing vertebrate skeletal
      muscle exhibit functional heterogeneity in both conductance and kinetics. To
      assess the contributions of receptors differing in subunit composition to the
      heterogeneity, various combinations of mouse alpha beta delta gamma epsilon
      subunit RNAs were tested for the ability to express functional receptors in
      Xenopus oocytes. 2. Two combinations of dual-subunit RNAs (alpha delta and alpha
      gamma) resulted in detectable ACh-activated currents and six different
      combinations of three or more subunit RNAs produced significant numbers of
      functional channels. The order of combinations yielding the greatest amount of
      current was alpha beta gamma > alpha beta delta = alpha delta epsilon > alpha
      delta gamma > alpha delta > alpha gamma. 3. The extent to which a channel type
      with three different subunits was expressed was highly dependent upon the ratios
      of RNAs coding for the different subunits. For alpha beta delta receptors the
      efficiency of expression was alpha: beta: delta (1/5:1/5:1) >> (1:1:1) >>
      (1/5:1:1/5) > (1:1/5:1/5). 4. The level of expression of three-subunit
      combinations was also critically dependent upon the order of RNAs injected. When
      alpha delta or alpha gamma RNA combinations were co-injected 2 days prior to the
      injection of beta RNA, the expression was 2-5 times greater than when alpha beta
      injection was followed by injection of delta or gamma RNA. 5. Single-channel
      measurements revealed that alpha beta delta channels were not expressed in the
      presence of alpha beta delta epsilon RNAs, even under conditions when the amount
      of delta RNA injected was 5-fold higher than the amount of epsilon RNA. 6. These
      data indicate that the functional expression of subunit-omitted receptors depends
      critically upon the relative amounts of the five different subunit RNAs.
      Receptors composed of three different subunits express in the presence of the
      subunit RNAs characteristic of embryonic muscle (alpha beta delta gamma), but are
      not observed with the combination of RNAs characteristic of adult muscle (alpha
      beta delta epsilon).

PMID- 7508505
TI  - Modification of the transient outward current of rat atrial myocytes by metabolic
      inhibition and oxidant stress.
AB  - 1. A putative function of the transient outward current (ITO) in cardiac myocytes
      is to modulate the shape of the action potential and, consequently, cardiac
      contractility. In addition, it has been suggested that this current may help
      protect against arrhythmias during periods of cardiac ischaemia. In our
      investigation of the possible anti-arrhythmic action of ITO, we have examined its
      response to metabolic inhibition and oxidant stress. 2. Whole-cell recordings
      were obtained from rat atrial myocytes using standard patch-clamp techniques.
      Inhibition of metabolism, using 10 mM 2-deoxy-D-glucose (2-DG) to block
      glycolysis with or without the addition of 2 mM cyanide to block oxidative
      phosphorylation, led to inhibition of ITO at a holding potential of -70 mV.
      Shifting the holding potential to -80 mV restored ITO, suggesting that metabolic
      inhibition had shifted the inactivation curve of ITO in a negative direction. 3.
      Quasi steady-state inactivation curves revealed a shift in ITO inactivation
      induced by complete metabolic inhibition with 2-DG and cyanide. Myocytes
      typically contracted shortly after the shift was observed. In the presence of
      Ruthenium Red, contraction was delayed and myocytes could undergo several
      exposures to the metabolic inhibitors, each time displaying a shift in ITO
      inactivation. The shifts ranged between -7 and -20 mV. 4. Recovery from
      inactivation was determined using a two-pulse protocol. The time constant of
      recovery at a holding potential of -80 mV reversibly shifted from 48 +/- 8 to 129
      +/- 21 ms during metabolic inhibition (n = 4). 5. The activation of ITO from a
      holding potential of -100 mV shifted in a negative direction during metabolic
      inhibition, from a half-activation voltage of 0.3 +/- 3.0 to -14.7 +/- 2.5 mV (n
      = 5). Such a -15 mV shift increases the amplitude of ITO by approximately 30% at
      0 mV. 6. A shift in ITO inactivation similar to that produced by metabolic
      inhibition could be shown when myocytes were subjected to oxidant stress induced
      by either 1 mM t-butyl hydroperoxide (TBHP) or the photoactivation of 100 nM Rose
      Bengal. Furthermore, an increase in pipette concentration of free Ca2+ from 20 to
      200 nM also shifted ITO inactivation in a negative direction. 7. These results
      raise the possibility that the rise in intracellular [Ca2+] occurring during both
      metabolic inhibition and oxidant stress modifies activation and inactivation of
      ITO.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7508506
TI  - Inward current activated by carbachol in rat intestinal smooth muscle cells.
AB  - 1. Carbachol (0.1 mM or 10 microM)-evoked inward currents were studied with
      standard and perforated whole-cell patch clamp techniques in smooth muscle cells
      isolated from rat small intestine. The intracellular free Ca2+ concentration was
      monitored simultaneously with the fura-2 method. 2. With a K(+)-containing
      pipette solution, carbachol produced an inward current at -60 mV and a large
      outward current at -20 mV. 3. When NaCl was substituted for KCl in the external
      and pipette solutions, carbachol elicited inward currents at holding potentials
      more inside-negative than 0 mV. The reversal potential of the carbachol-induced
      current altered when external chloride (-0.9 mV) was replaced by iodide (-21.2
      mV), thiocyanate (-27.0 mV) and glutamate (18.2 mV). The carbachol-induced
      current at -60 mV was slightly decreased by the replacement of external NaCl with
      Tris-Cl. 4. The carbachol-induced inward current at -60 mV was accompanied by an
      increase in the intracellular concentration of free Ca2+. Both responses to
      carbachol were observed 2 min after exposure of the cells to a Ca(2+)-free
      solution containing 2 mM EGTA. 5. Intracellular application of heparin inhibited
      the inward current and Ca2+ transient responses to carbachol but not those to
      caffeine (10 mM). An inward current and Ca2+ transient were elicited after the
      patch membrane was ruptured at -60 mV, using a patch pipette containing inositol
      1,4,5-trisphosphate (InsP3). 6. It is concluded that the carbachol-induced inward
      current is due to increases in membrane Cl- and Na+ conductances. Ca2+ released
      from InsP3-sensitive stores may play a role in increasing both conductances.

PMID- 7508507
TI  - Mitogenic factors regulate ion channels in Schwann cells cultured from newborn
      rat sciatic nerve.
AB  - 1. Patch clamp studies were carried out in Schwann cells cultured from newborn
      rat sciatic nerve to determine the effects of mitogens on voltage-gated currents
      without the confounding influences of axonal contact and myelin present in vivo.
      The relevance of the various Schwann cell currents to proliferation was assessed
      using assays of [3H]thymidine incorporation. 2. Treatment of cultured Schwann
      cells with known mitogens, namely axon fragments (AF), myelin fragments (MF), or
      glial growth factor in combination with forskolin (GGF+F), increased the
      magnitudes of delayed rectifying potassium (K+) and sodium (Na+) currents. 3. In
      both control and mitogen-treated cells, the magnitude of net outward current
      paralleled clearly the magnitude of the cells' proliferative response. 4. The K+
      channel-blocking quaternary ammonium ions, tetrabutylammonium (TBuA),
      tetrapentylammonium (TPeA) and tetrahexylammonium (THeA), but not the Na+ channel
      blocker tetrodotoxin (TTX), reduced proliferation in a dose-dependent fashion
      offering further evidence for a role for K+ channels in Schwann cell
      proliferation. 5. Voltage-gated chloride (Cl-) currents were observed in both
      control and mitogen-treated cells. Addition of the Cl- channel blockers, 4
      acetamido-4'-isocyanatostilbene-2,2'-disulphonate (SITS) or 4,4'
      diisothiocyanatostilbene-2,2'-disulphonate (DIDS), to the culture media enhanced
      proliferation. 6. The possible intermediary role of the Schwann cell resting
      potential was explored in ion substitution experiments by increasing the K+
      concentration of the media and by adding ouabain. Both manipulations inhibited
      Schwann cell mitosis. 7. Comparison of the expression of functional ion channels
      in vitro with that previously described for Schwann cells in vivo suggests a
      difference in the Schwann cell response to the membrane fragment mitogens and
      their intact counterparts in regard to the regulation of ion channels. MF up
      regulates the number of functional channels, whereas the elaboration of myelin
      (or a factor related to its presence) in vivo appears to down-regulate channel
      expression, at the cell soma of myelinating Schwann cells. In addition, axonal
      contact may be required for normal expression of functional inwardly rectifying
      K+ channels.

PMID- 7508508
TI  - Electrophysiological effects of tachykinins and capsaicin on guinea-pig bronchial
      parasympathetic ganglion neurones.
AB  - 1. We evaluated the effects of neurokinins, tachykinin analogues, or capsaicin on
      passive membrane properties of guinea-pig bronchial parasympathetic neurones
      using intracellular recording techniques. 2. Substance P (SP) and the tachykinin
      analogue, acetyl-[Arg6,Sar9,Met(O2)11]-SP(6-11) (ASMSP), at concentrations
      selective for the neurokinin (NK)-1 receptor subtype, depolarized the resting
      potential (3 and 5 mV, respectively) with no change in input resistance.
      Neurokinin A and beta Ala8NKA(4-10), at concentrations selective for the NK-2
      receptor subtype (0.1 microM), were without effect. 3. Neurokinin B (NKB) and
      [Asp5,6,methyl-Phe8]SP(5-11) (senktide analogue), at concentrations selective for
      NK-3 receptor subtype, elicited maximum depolarizations of 16 +/- 2 mV for both
      agonists. The peak of the depolarization was associated with an decrease in
      membrane resistance (35 +/- 4 and 50 +/- 7%, respectively). 4. Capsaicin (1
      microM) elicited a 3-24 mV depolarization of the resting potential of thirteen of
      eighteen bronchial ganglion neurones and decreased the input resistance of seven
      of thirteen of these neurones. The effects of capsaicin were reduced by
      desensitization with senktide analogue at a concentration selective for the NK-3
      receptor subtype, whereas a non-peptide NK-1 receptor antagonist had no effect.
      5. Using voltage clamp analysis, capsaicin and senktide analogue evoked an inward
      current and an increase in membrane conductance at the resting membrane
      potential. The reversal potential for senktide analogue was estimated to be + 4
      mV. 6. These data support the hypothesis that neurokinin-containing nerve
      terminals are localized within guinea-pig bronchial parasympathetic ganglia and,
      when released, the predominant effect of the neurokinins is by activation of NK-3
      receptors.

PMID- 7508509
TI  - B cell hyperactivity is a function of T cell derived cytokines in systemic lupus
      erythematosus.
AB  - OBJECTIVE: T cell abnormalities and abnormal production of cytokines is a key
      event of B cell hyperactivity and antibody synthesis in systemic lupus
      erythematosus (SLE). We investigated T cell function and role of interleukin 4
      (IL-4) and IL-6 in B cell induced Ig synthesis from SLE. METHODS: Phenotypes and
      expression of activation antigens on T cells and monocytes was determined by
      specific monoclonal antibodies using indirect immunofluorescence technique. IL-4,
      IL-6 and tumor necrosis factor-alpha (TNF alpha) assays and in vitro Ig synthesis
      was carried out by enzyme linked immunosorbent assays. RESULTS: CD25, CD38 and
      CD71 expressing T cells and monocytes were increased in circulation of patients
      with SLE. Patients with SLE associated with prominent clinical presentation like
      lymphadenopathy had a higher percentage of gamma delta T cells in blood.
      CD4+CD29+ T cell subsets, which were the major T cells secreting IL-6, were
      increased in the circulation and provide effective helper function to B cells in
      their enhanced in vitro Ig synthesis in SLE. CONCLUSION: Our results demonstrate
      that CD4+CD29+ T cell subsets produced elevated levels of IL-6 in SLE and that IL
      6 overproduction may contribute to the B cell hyperactivity in enhanced antibody
      synthesis characteristic of this autoimmune disease.

PMID- 7508510
TI  - Autoantibodies to nuclear lamins and to intermediate filament proteins.

PMID- 7508511
TI  - Myopathy presenting as developmental delay and short stature.

PMID- 7508512
TI  - Structure determination, pharmacological evaluation, and structure-activity
      studies of a new cyclic peptide substance P antagonist containing the new amino
      acid 3-prenyl-beta-hydroxytyrosine, isolated from Aspergillus flavipes.
AB  - Two novel cyclic heptapeptides, peptides 1a and 1c, were isolated from an
      Aspergillus flavipes culture, originally isolated from soil, and their structures
      established by chemical and spectroscopic evidence. Peptide 1a contains a new
      amino acid, 3-prenyl-beta-hydroxytyrosine, and is a competitive antagonist to
      substance P at the human NK1 receptor, with an inhibitor affinity constant (Ki)
      of 8 +/- 4 microM. Methylation of 1a gave the monomethyl derivative 1b, which is
      a more potent competitive antagonist, with a Ki of 0.12 +/- 0.03 microM at the
      human NK1 receptor. Herein we report the structure determinations of 1a and 1c,
      and some structure-activity results. Several analogs of 1a were prepared by
      derivatization and synthesis. Structure-activity results for these analogs
      confirmed that the 3-prenyl-beta-hydroxytyrosine moiety is critical for the
      biological potency of 1a and 1b.

PMID- 7508513
TI  - Automatic identification of group I intron cores in genomic DNA sequences.
AB  - Automatic identification of the ribozyme core of group I catalytic introns in
      genomic sequences is shown to be feasible in spite of the scarcity of strictly
      conserved features in the sequence and secondary structure of group I introns. An
      algorithm is described that successfully identified 132 out of the 143 currently
      reported group I cores with a false positive rate of only 10(-6) per nucleotide.
      The recognition process consists in generating and rating large sets of potential
      local solutions which are gradually combined into more complex structures until
      an entire core (six to seven pairings, six connecting segments, three terminal
      loops) has been assembled. The extent to which successful recognition may be
      prevented by sequencing errors is assessed. Also discussed are (1) possible
      relationships between scores allocated by the program and ability to self-splice
      in vitro and (2) the potential for objectively assessing the degree of
      relatedness to group I of structures claimed to resemble group I introns.

PMID- 7508514
TI  - Location of the streptomycin ribosomal binding site explains its pleiotropic
      effects on protein biosynthesis.
AB  - Photoaffinity-labeling experiments using three nitroguaiacol ether streptomycin
      derivatives with spacers of different lengths between the antibiotic and the
      photoreactive moiety (8, 12 and 17 A) allow us to: (1) unambiguously locate the
      boundaries of the antibiotic binding site; and (2) test the topographical
      consistency of the photolabeling results. The streptomycin binding site is
      located in the interface between the ribosomal subunits, close to proteins S5 in
      the 30 S and to L11 in the 50 S ribosomal subunits. This location explains most
      of the antibiotic's pleiotropic effects on protein biosynthesis, especially those
      related to the tRNA selection mechanism, and it also correlates with the location
      of the ribosomal components involved in the different streptomycin phenotypes.

PMID- 7508515
TI  - Bovine RNase MRP cleaves the divergent bovine mitochondrial RNA sequence at the
      displacement-loop region.
AB  - RNase MRP is a site-specific ribonucleoprotein endoribonuclease that cleaves
      mitochondrial RNA from the origin of leading-strand DNA synthesis contained
      within the displacement-loop region. Bovine mitochondrial DNA maintains the
      typical gene content and order of mammalian mitochondrial DNAs but differs in the
      nature of sequence conservation within this displacement-loop regulatory region.
      This markedly different sequence arrangement raises the issue of the degree to
      which a bovine RNase MRP would reflect the physical and functional properties
      ascribed to the enzymes previously characterized from mouse and human. We find
      that bovine RNase MRP exists as a ribonucleoprotein, with an RNA component of 279
      nucleotides that is homologous to that of mouse or human RNase MRP RNA.
      Characterization of the nuclear gene for bovine RNase MRP RNA showed conservation
      of sequence extending 5' of the RNase MRP RNA coding sequence, including the
      presence of a cis-acting element known to be important for the expression of some
      mitochondrial protein-coding nuclear genes. Bovine or mouse RNase MRP cleaves a
      standard mouse mitochondrial RNA substrate in the same manner; each also cleaves
      a bovine mitochondrial RNA substrate identically. Since bovine and mouse RNase
      MRPs process both bovine and mouse substrates, we conclude that the structural
      features of the mitochondrial RNA substrate required for enzymatic cleavage have
      been well conserved despite significant overall primary sequence divergence.
      Inspection of the bovine RNA substrate reveals conservation of only the most
      critical portion of the primary sequence as indicated by earlier studies with
      mouse and human RNase MRPs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508516
TI  - Sequence evolution of mitochondrial tRNA genes and deep-branch animal
      phylogenetics.
AB  - Mitochondrial DNA sequences are often used to construct molecular phylogenetic
      trees among closely related animals. In order to examine the usefulness of mtDNA
      sequences for deep-branch phylogenetics, genes in previously reported mtDNA
      sequences were analyzed among several animals that diverged 20-600 million years
      ago. Unambiguous alignment was achieved for stem-forming regions of mitochondrial
      tRNA genes by virtue of their conservative secondary structures. Sequences
      derived from stem parts of the mitochondrial tRNA genes appeared to accumulate
      much variation linearly for a long period of time: nearly 100 Myr for transition
      differences and more than 350 Myr for transversion differences. This
      characteristic could be attributed, in part, to the structural variability of
      mitochondrial tRNAs, which have fewer restrictions on their tertiary structure
      than do nonmitochondrial tRNAs. The tRNA sequence data served to reconstruct a
      well-established phylogeny of the animals with 100% bootstrap probabilities by
      both maximum parsimony and neighbor-joining methods. By contrast, mitochondrial
      protein genes coding for cytochrome b and cytochrome oxidase subunit I did not
      reconstruct the established phylogeny or did so only weakly, although a variety
      of fractions of the protein gene sequences were subjected to tree-building. This
      discouraging phylogenetic performance of mitochondrial protein genes, especially
      with respect to branches originating over 300 Myr ago, was not simply due to high
      randomness in the data. It may have been due to the relative susceptibility of
      the protein genes to natural selection as compared with the stem parts of
      mitochondrial tRNA genes. On the basis of these results, it is proposed that
      mitochondrial tRNA genes may be useful in resolving deep branches in animal
      phylogenies with divergences that occurred some hundreds of Myr ago. For this
      purpose, we designed a set of primers with which mtDNA fragments encompassing
      clustered tRNA genes were successfully amplified from various vertebrates by the
      polymerase chain reaction.

PMID- 7508517
TI  - Why monitor angiogenic factors in patients' urine?

PMID- 7508518
TI  - Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the
      urine of patients with a wide spectrum of cancers.
AB  - BACKGROUND: Experimental evidence supports the hypothesis that the development of
      blood vessels is fundamental to the growth and metastasis of solid tumors.
      Elevated levels of the angiogenic peptide basic fibroblast growth factor (bFGF)
      have been significantly correlated with the status and extent of disease in
      bladder cancer. PURPOSE: We measured the bFGF levels in patients with cancer in
      organs other than the bladder to determine whether elevated levels accompany
      these cancers. METHODS: Urine samples were collected from 950 patients having a
      wide variety of solid tumors, leukemia, or lymphoma and from a control group of
      87 healthy volunteers and 198 patients with non-cancer-related diseases. Levels
      of bFGF in samples prepared from the urine were measured using an enzyme
      bioassay. RESULTS: Male control subjects had a median bFGF level of 151 pg/g and
      female control subjects a median of 237 pg/g, with a combined 90th percentile of
      619 pg/g. An elevated level of bFGF was found in the urine of some of the
      patients with every type of tumor studied except cervical carcinoma. For example,
      patients with active local cancers had a median level of 312 pg/g. Those with
      active, metastatic cancers had a median level of 479 pg/g and a 90th percentile
      level of 14143 pg/g. After "elevated" was defined to mean higher than the 90th
      percentile level for controls, 31% of patients with local active and 47% of
      patients with metastatic active cancers showed elevated bFGF levels. Survival
      among cancer patients at the median follow-up time was 85%-88% for those with
      "normal" and 71%-72% for those with "elevated" urine bFGF levels. IMPLICATIONS:
      Our results suggest that bFGF in urine deserves further evaluation of its
      potential use as a monitor of therapy or as a predictor of outcome once a cancer
      has been diagnosed.

PMID- 7508519
TI  - Breast carcinoma: comparative study of tumor vasculature using two endothelial
      cell markers.

PMID- 7508520
TI  - Erythrocyte polyamines and prognosis in stage D2 prostatic carcinoma patients.
AB  - We studied 43 patients with newly diagnosed, untreated, stage D2 prostatic
      carcinoma, and correlated the initial performance status, hemoglobin, prostate
      specific antigen levels, tumor Gleason grade, extent of disease on the bone scan,
      and erythrocyte spermidine and spermine levels with progression. Three patients
      died of unrelated causes and were excluded from the study, 16 remained in
      remission with a mean 28 +/- 11 months of followup and 24 had progression (18, or
      75%, of whom died of the cancer) with a mean 12 +/- 9 months of followup (p <
      0.05 for followup) after initiation of hormonal therapy. Pretreatment performance
      status, hemoglobin, and erythrocyte spermidine and spermine levels were
      correlated with progression, hemoglobin and spermine being the most significant
      independent variables (p = 0.006 and p = 0.001, respectively). Concerning cause
      specific survival, only hemoglobin and spermine erythrocyte levels were
      significant independent variables (p = 0.02 and p = 0.0025, respectively). If
      confirmed, polyamine erythrocyte levels obtained by a simple blood sample could
      discriminate at diagnosis patients with a high risk of rapid hormonal relapse who
      may benefit from a more aggressive primary management.

PMID- 7508521
TI  - Survival after transurethral resection of the prostate: a 10-year followup.
AB  - Among 141 men who underwent transurethral resection of the prostate from late
      1979 to early 1980 followup for 10 years was done, registering total mortality
      rate and individual dates of death. The mortality of the group was compared to an
      age-matched group from the background population of men for each of the 10 years.
      During the observation period the mortality of the group as a whole as well as
      that of the patients 65 years old or older at operation were equal to that of the
      background population at all times. Withholding recommendation of transurethral
      resection of the prostate in favor of other types of prostatic surgery on the
      grounds of a higher long-term mortality rate is not supported by our material.

PMID- 7508522
TI  - Radical radiation therapy in the management of prostatic adenocarcinoma: the
      initial prostate specific antigen value as a predictor of treatment outcome.
AB  - We studied 161 prostate cancer patients treated by radical irradiation alone
      without endocrine therapy in whom pretreatment and posttreatment prostate
      specific antigen (PSA) values were measured, and who had a minimum followup of 2
      years. Outcome was analyzed in an actuarial fashion using clinical disease-free
      survival and biochemical disease-free survival (freedom from an increasing PSA
      level or a PSA level of greater than 1.0 ng./ml. 2 years following irradiation)
      as end points. Of the patients 54% achieved a post-irradiation nadir value in the
      range 0 to 1.0 ng./ml. and 29% had a nadir value that was undetectably low (less
      than 0.5 ng./ml.). The likelihood of achieving these values was greater among
      patients with early stage than locally advanced tumors. For all T stages the
      likelihood of being disease-free at 4 years was substantially and significantly
      lower when PSA was used as an end point than when clinical evaluation alone was
      used: stages T1 and T2 (85 patients) 41% versus 71%, and stages T3 and T4 (76
      patients) 15% versus 61%. For the whole group at 4 years clinical control was 67%
      but biochemical control was only 26% (p < 0.05). The likelihood of being free of
      biochemical evidence of persistent disease at 4 years was a function of the
      initial PSA value (PSA less than 4.0 in 81% of the cases, 4.1 to 10.0 in 43%,
      10.1 to 20.0 in 31%, 20.1 to 50.0 in 6% and greater than 50.0 in 0%). For stages
      T1 and T2 cancer patients with an initial PSA level of less than 15 ng./ml. (67%
      of all early stage cases) this value was 65% and it was even higher (73%) when
      poorly differentiated tumors were excluded. When the initial PSA level for stages
      T1 and T2 tumors was greater than 15 ng./ml. the projected 4-year rate of freedom
      from biochemical failure was only 7%. For stages T3 and T4 cancer patients the
      corresponding figures were 39% for those with an initial PSA level of less than
      15 ng./ml. and 0% for those with an initial PSA level of greater than 15 ng./ml.
      The prognostic power of the initial PSA level was independent of stage, grade,
      patient age and prior transurethral resection of the prostate in a multivariate
      analysis. An initial serum PSA level of more than 15 ng./ml. is, therefore, a
      powerful predictor of probable failure with conventional radiation therapy. Serum
      PSA monitoring is a sensitive detector of early relapse.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7508523
TI  - Radical prostatectomy as a monotherapy for locally advanced (stage T3) prostate
      cancer.
AB  - Within a prospective protocol initiated in 1977, 100 patients with locally
      extensive prostate cancer (stage T3, 1982 tumor, nodes and metastasis
      classification) were treated by pelvic node dissection and radical prostatectomy
      as monotherapy. Adjuvant treatment was not given until disease progression.
      Radical prostatectomy, except for 3 young patients with a single micrometastasis,
      was not done if positive lymph nodes were found at frozen section. Six patients
      had positive lymph nodes at permanent sections but not at frozen section. Average
      followup was 43.9 months (range 1 to 155 months). Histological grade was
      determined according to the Mostofi system. Progression was determined
      biochemically (prostate specific antigen elevation) and clinically by evidence of
      metastatic disease, either histologically proved or evidenced as new hot spots on
      bone scan or chest x-rays. Of the 100 patients 41 did not undergo radical
      prostatectomy: 39 because of positive lymph nodes and 2 because of evidence of a
      stage pT4 tumor at surgical exploration. Of those 59 patients who underwent
      radical prostatectomy 9 had positive lymph nodes, while 2 had stage pT4, 39 stage
      pT3 and 9 stage pT2 tumors. Only 1 of the 9 patients with lymph node metastases
      is free of biochemical or clinical progression. Disease also progressed in both
      stage pT4, 27 of 39 stage pT3 and none of the 9 stage pT2 cases. A total of 22
      patients was free of clinical or biochemical progression. Clinical progression
      was evidenced in approximately half of the cases as distant and local
      progression. Data on stage T3 disease were compared to those of 129 patients with
      stages T0 to T2 disease. There was a significant difference in interval to
      clinical progression for these 2 groups (p = 0.001). However, if grade 3 cases
      were excluded from the stage T3 group, this difference disappeared. Prognostic
      factors analyzed were pretreatment and posttreatment grade, pretreatment prostate
      specific antigen and prostatic acid phosphatase levels, positive margins, seminal
      vesicle invasion and nodal status. The analysis allows one to identify groups of
      patients who may benefit and others who certainly do not benefit from radical
      prostatectomy in this disease category. In the latter group effective adjuvant
      treatment is urgently indicated.

PMID- 7508524
TI  - Prostate cancer.

PMID- 7508525
TI  - Laparoscopic pelvic lymph node dissection: a review of 103 consecutive cases.
AB  - Laparoscopic pelvic lymph node dissection is a recently introduced technique for
      the surgical evaluation of the regional pelvic lymph nodes in genitourinary
      malignancies. We report the results of a laparoscopic pelvic lymph node
      dissection performed on 103 consecutive patients for staging of clinically
      localized prostatic, bladder and penile carcinomas. In 20 patients (group 1) the
      adequacy of the laparoscopic pelvic lymph node dissection was evaluated with a
      subsequent open dissection. In this group 87 to 95% of the lymph nodes within a
      modified template could be reliably removed laparoscopically. In 73 patients
      (group 2) laparoscopic pelvic lymph node dissection was performed as a solitary
      operation. Mean hospitalization was 1.6 +/- 2.4 days, while postoperative
      narcotic requirements were minimal. Mean operative time for bilateral
      laparoscopic pelvic lymph node dissection was 156 +/- 41.2 minutes. The overall
      complication rate in these 2 groups was 13.5%. Group 3 includes 10 patients (9.7%
      of the total) in whom laparoscopic pelvic lymph node dissection was unsuccessful.
      The minimally invasive surgical techniques of laparoscopic pelvic lymph node
      dissection seem to provide adequate staging accuracy in patients with
      genitourinary neoplasms. The complication rate and recovery period appear to be
      decreased relative to those for open surgical lymphadenectomy.

PMID- 7508526
TI  - He sold his bike for a low prostate specific antigen.

PMID- 7508527
TI  - Re: False-positive prostate specific antigen values in the sera of women with
      renal cell carcinoma.

PMID- 7508529
TI  - [A case of PIVKA-II and AFP producing gastric carcinoma].

PMID- 7508528
TI  - The effects of intravesical pretreatment with pentosan polysulfate on the
      bacillus Calmette-Guerin induced immune reaction of the guinea pig.
AB  - Immunotherapy with intravesical instillation of bacillus Calmette-Guerin (BCG) is
      an effective treatment for superficial bladder carcinoma. In the present study
      the BCG-induced immunological reaction in the guinea pig (PPD skin test, bladder
      wall infiltrates and number of cells in the iliac lymph nodes) was investigated
      after intravesical pretreatment with pentosan polysulphate (PPS), which modulated
      BCG attachment to the bladder wall. Pentosan polysulfate is a molecule comparable
      to the naturally occurring glycosaminoglycans (GAGs) of the bladder mucosa. The
      data obtained after six weekly instillations of BCG-RIVM (5 x 10(6) - 5 x 10(7)
      cfu) with or without preinstillation with PPS (10 mg. in 1 ml. for 0.5 hour)
      suggested an elevation of the immunological reaction to intravesical BCG. A
      strong binding capacity of PPS to the mammalian bladder wall was observed. In
      addition, and in contrast to bacteria commonly causing cystitis, a significant
      binding of PPS to mycobacteria was found: 3.5, 3.6 and 3.1 micrograms./ml. dry
      weight of BCG Connaught, RIVM and Pasteur, compared with 0.2, 0.3, 0.7 and 0.0
      microgram./mg. dry weight of Escherichia coli, Streptococcus faecalis, Klebsiella
      pneumoniae and Proteus. The results suggest that PPS enhances the attachment of
      BCG to the bladder wall, resulting in an increased BCG-induced immunological
      reaction in the guinea pig. It may be speculated that pretreatment with PPS may
      increase the efficacy of BCG therapy in man, especially in those patients not
      exhibiting an immunological reaction.

PMID- 7508530
TI  - [Comparative assessment of the characteristics in various assay kits for prostate
      specific antigen].
AB  - Six kinds of assay kits based on different detecting principle for PSA were
      evaluated. Polyclonal antibody was used in 2 kits (Eiken, Markit-F) and
      monoclonal antibody in 4 kits (Ball Elsa, Delfia, Markit-M, Tandem-R). To
      evaluate their characteristics, sera of 12 female patients, 5 prostatectomized
      patients and 2 high stage prostate cancer patients were measured by these kits.
      On the female sera the polyclonal assay kits yielded values higher than the
      defined minimal sensitive value, but the kits of monoclonal antibody detected
      nothing. Dilution test of sera with high PSA level showed satisfactory results in
      every kit but the values of 6 assays were different to each other. For monitoring
      the recurrence or recrudescence of the prostatic cancer, the monoclonal antibody
      kits may be preferable to the polyclonal antibody kits. These results showed that
      we must understand the characteristics of every assay kit which is used
      clinically.

PMID- 7508531
TI  - [A case of teratoma of the testis with retroperitoneal lymph nodes involved with
      malignant teratoma after chemotherapy].
AB  - This report describes a case of teratoma with retroperitoneal lymph nodes
      involved with malignant teratoma (enteric adenocarcinoma) after extensive
      chemotherapy for the original testicular cancer. A 18-year-old man with a mixed
      cell tumor (embryonal carcinoma+teratoma+yolk sac tumor) received three courses
      of VAB-6 chemotherapy for bulky mass following inguinal orchiectomy. He was
      referred to Tochigi Cancer Center for treatment of a residual mass. He was
      treated with resection of the mass combined with left nephrectomy due to severe
      adhesion and pathological diagnosis of the resected lymph node was mature
      teratoma with a massive necrotic tissue. Two courses of BEP chemotherapy were
      given to the patient following the surgery. Six months after completion of
      chemotherapy, a retroperitoneal mass of 1.5 cm in diameter, was detected by CT
      scan. Standard retroperitoneal lymph node dissection was performed and the
      pathological diagnosis of the lymph node was teratoma with malignant
      transformation containing enteric adenocarcinoma. Teratomatous portion of the
      primary lesion was precisely re-examined and adenocarcinoma, similar histology to
      the retroperitoneal mass, was identified. He received two courses of EAP
      chemotherapy (Cis-platin+etoposide+doxorubicin) as an adjuvant chemotherapy
      following the surgery and he is alive with no evidence of recurrence for 21
      months. Presence of non germ cell malignancy after chemotherapy in testicular
      cancer has been regarded as a rare phenomenon. Flow cytometric DNA analyses of
      both embryonal carcinoma and teratoma in the primary lesion, mature teratoma and
      teratoma with malignant transformation of the retroperitoneal lymph node
      disclosed that these tumors were all aneuploid tumors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508532
TI  - Stem cell factor improvement of proliferation and maintenance of hemopoietic
      progenitors in myelodysplastic syndromes.
AB  - Human recombinant stem cell factor (rSCF) was tested for its capability of
      improving the defective growth of hemopoietic progenitors in 28 cases of
      myelodysplastic syndromes (MDS). In vitro growth and response to rSCF were quite
      variable. However, in most cases, rSCF stimulated CFU-GM growth induced by rG
      CSF, rGM-CSF, rIL-3, 5637 conditioned medium (50-1400% enhancement). rSCF effect
      was slightly more evident on day 14 CFU-GM and in the presence of rIL-3. BFU-E
      growth induced by rEPO or rIL-3 + rEPO was enhanced by rSCF in about 50% of
      cases, in linear correlation with the levels of patients' hemoglobin. rSCF did
      not increase CFU-E growth, whereas it slightly stimulated CFU-Mk in 33% of the
      cases. EPO, SCF and, particularly, their combination, enhanced the recovery of
      normal CFU-E and BFU-E after 7 days of liquid culture. This was less evident in
      cultures of MDS patients. Conversely, CFU-GM generation in long term liquid
      cultures, although highly variable, was stimulated by rSCF and, above all, by
      rSCF + rG-CSF, similarly to what was observed with normal bone marrow samples.
      SCF seems to enhance in vitro erythropoiesis only in MDS cases presenting without
      severe anemia. It has little effect on megakaryocytopoiesis, while it seems to be
      more active on CFU-GM growth and maintenance.

PMID- 7508533
TI  - AML: immunophenotypic heterogeneity and prognostic significance of c-kit
      expression.
AB  - Antigenic profiles in AML that have generally accepted prognostic significance,
      and allow treatment stratification, have not yet been defined. In a previous
      report of Ashman et al., the proto-oncogene c-kit defined by binding of the moab
      YB5.B8 was expressed on about one third of AML cases, mainly of the
      undifferentiated FAB-subtypes and associated with poor prognosis and overall
      survival. In this study, the moab 17F11 also directed against the c-kit structure
      stained 41/47 AML and 6/8 CML blast specimens, whereas all investigated 40 ALL
      samples were c-kit negative. c-kit was not restricted to any particular,
      undifferentiated FAB-subtype, but found in 9/9 AML-M0/M1, 18/19 AML-M2, 0/1 AML
      M3, 11/13 AML-M4 and 3/5 AML-M5 subtypes. Immunophenotypical analysis showed no
      restriction of c-kit expression to immature, CD34+ precursors, but c-kit was also
      expressed on CD4+ CD34- precursor cells differentiating towards the monocyte
      lineage. In addition, multi-color labelings revealed an extraordinary
      heterogeneity of concomitant antigen expression on c-kit+ cells 10/36 c-kit+
      CD34+ samples expressing CD56 and 16/36 c-kit+ CD34+ samples being CD7 positive;
      two c-kit+ CD34+ specimens carried the B-cell antigen CD19. In correlation to
      clinical outcome c-kit expression as single parameter was not predictive for poor
      response to therapy and short survival as previously suggested.

PMID- 7508534
TI  - The differentiation inducing effect of bryostatin 5 on human myeloid blast cells
      is potentiated by vitamin D3.
AB  - Bryostatin 5 is a macrocyclic lactone which activates protein kinase C (PKC). PKC
      activation has been implicated in leukemic cell differentiation. We have examined
      the effect of PKC activation by bryostatin 5 on human acute myeloid cell
      differentiation in the presence and absence of vitamin D3. In vitro treatment of
      20 patient samples of acute myeloid leukemias in a 4 days culture system with 10
      nM bryostatin 5 induced strongly adherent macrophage-like cells in all cases.
      Bryostatin 5 induced a significant (p = 0.00006) increment in esterase activity
      in a majority of the samples, which was further enhanced by vitamin D3. CD14
      expression was significantly (p = 0.035) enhanced with the combination of
      bryostatin 5 and vitamin D3. Nitroblue tetrazolium (NBT) reducing ability was,
      however, nearly abolished (p = 0.0007). A loss of CD34 expression occurred during
      cell culture; this loss was enhanced by vitamin D3, but prevented partly by
      bryostatin 5. Together these findings indicate that exposure to bryostatin 5
      leads to a strong macrophage-like cell differentiation in human myeloid leukemia
      and that VD3 has an additional effect. These findings strengthen the potential
      role of bryostatins as possible antileukemic agents.

PMID- 7508535
TI  - Altered susceptibility of differentiating HL-60 cells to apoptosis induced by
      antitumor drugs.
AB  - It has been reported that human promyelocytic leukemic HL-60 cells which undergo
      differentiation fail to respond by apoptosis when treated with antitumor drugs,
      predominantly DNA topoisomerase inhibitors. Because S phase cells are selectively
      sensitive to these drugs, and during differentiation there is a reduction in the
      proportion of cells in S phase, the reported decrease in the number of apoptotic
      cells could simply be a reflection of the paucity of sensitive cells in these
      cultures. Using cytometric methods which allow apoptosis to be related to cell
      cycle position, we have compared the apoptotic response of HL-60 cells growing
      exponentially and induced to myeloid differentiation by dimethyl sulfoxide
      (DMSO). The cells were treated with: (i) the DNA topoisomerase I inhibitor
      camptothecin (CAM), which selectively triggers apoptosis or S phase cells; (ii)
      the nucleoside antimetabolite 5-azacytidine (AZC) and hyperthermia, both of which
      preferentially affects G1 cells; and (iii) gamma radiation, which causes
      apoptosis predominantly of G2 + M cells. The cells exposed to 1.4% DMSO for 24 or
      48 h were significantly more resistant to response by apoptosis, regardless of
      the nature of the agent and regardless of their position in the cell cycle. Thus,
      induction of differentiation lowers the cell's ability to respond to a variety of
      damaging agents by apoptosis and this effect is not correlated with cell cycle
      position. In addition, the difference in response was unrelated to expression of
      the apoptosis-modulating protein bcl-2, which appeared unchanged following 48 h
      exposure to DMSO. On the other hand, when the cells were pretreated with low
      concentrations of CAM or AZC, washed free of drug, and then treated with DMSO,
      the proportion of cells undergoing apoptosis was markedly increased, relative to
      drug-treated cells returned to DMSO-free medium. The present data may indicate
      that while the drug-induced damage screening mechanisms, which are linked to
      triggering apoptosis, may be more proficient in proliferating cells, the
      effectors of apoptosis are more expressed in cells undergoing differentiation.
      The data also suggest that the efficiency of chemotherapeutic agents or radiation
      may be reduced if a differentiating agent is used in combination therapy and is
      administered first. An enhancement of apoptosis, however, may be expected if the
      differentiating drug is administered in the reverse sequence.

PMID- 7508537
TI  - Nephrotoxic effects of immunosuppression.

PMID- 7508536
TI  - Nephrotoxic effects of primary immunosuppression with FK-506 and cyclosporine
      regimens after liver transplantation.
AB  - OBJECTIVE: We conducted a treatment trial to determine the relative toxicity of
      FK-506 and cyclosporine A (CSA) in liver transplant recipients. DESIGN: Between
      October 1990 and October 1991, 37 patients were enrolled in an open-labeled,
      randomized study of two immunosuppressive regimens after liver transplantation.
      MATERIAL AND METHODS: Of the 23 men and 14 women, 20 received FK-506 plus
      prednisone, and 17 received CSA plus prednisone and azathioprine. Renal function
      was assessed before and after transplantation (day 1, month 1, month 4, and month
      12) by measurements of serum creatinine (SCr) and glomerular filtration rate
      (GFR) as determined by urinary iothalamate or creatinine clearance (or both). FK
      506 trough plasma levels (enzyme immunoassay) were to be maintained between 0.2
      and 5.0 ng/mL, and CSA trough blood levels (whole blood high-performance liquid
      chromatography) were to be maintained between 250 and 400 ng/mL. Severe
      nephrotoxicity was defined as sudden decreases in urine output to less than 10
      mL/h or rapid increases in SCr (more than 0.5 mg/dL daily) that necessitated
      withdrawal of study medication for more than 48 hours. Mean patient age and
      values for SCr and GFR were comparable between the two groups at entry. RESULTS:
      Both study groups demonstrated a similar deterioration in renal function during a
      12-month follow-up, although patients who received FK-506 had a significantly (P
      < 0.05) lower GFR when measured at 12 months than did patients treated with CSA
      (45 +/- 4 versus 64 +/- 6 mL/min per body surface area). Mild nephrotoxicity that
      responded to decreased drug doses was noted in 9 CSA-treated patients (53%) and
      10 FK-506-treated patients (50%). Severe nephrotoxicity that necessitated drug
      withdrawal occurred in only four patients, all of whom were in the FK-506 group.
      These severe nephrotoxic reactions to FK-506 occurred early after
      transplantation, often during intravenous administration of the drug, and were
      not associated with poor liver allograft function or drug levels outside the
      therapeutic range. CONCLUSION: Both FK-506 and CSA are significantly nephrotoxic
      in liver transplant recipients. In this trial, however, we observed an early
      development of severe nephrotoxic reactions only in some patients who received FK
      506.

PMID- 7508538
TI  - Moderate caloric restriction increases type 1 IGF receptors and protein synthesis
      in aging rats.
AB  - Insulin-like growth factor-1 (IGF-1) is an anabolic hormone that mediates the
      actions of growth hormone (GH) and is found at lower concentrations in aged
      animals. These decreases in GH and IGF-1 appear to have important physiological
      consequences for aging, since protein synthesis decreases with age, and
      administration of GH and/or IGF-1 has been shown to increase protein synthesis.
      The present study was designed to determine (a) the relationship between the age
      related changes in rates of tissue protein synthesis and plasma IGF-1
      concentrations, (b) type 1 IGF receptor density in tissues and (c) whether long
      term moderate caloric restriction, which is known to increase life-span, affects
      these relationships. Male Brown Norway rats were fed ad libitum or caloric
      restricted (60% ad libitum) from 14 weeks of age and sacrificed at different
      ages. In ad libitum fed animals there were age-related decreases in plasma IGF-1
      concentrations (14%) and in the rates of protein synthesis of the heart (36%) and
      liver (38%). Type 1 IGF receptor density remained constant in all tissues with
      age. The caloric-restricted animals exhibited plasma IGF-1 concentrations 33 to
      42% lower than the ad libitum fed animals. However, rates of protein synthesis
      increased by 70 and 30% in heart and diaphragm, and this increase was associated
      with 60 to 100% increases in type 1 IGF receptor densities when compared with ad
      libitum fed animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508539
TI  - The arginine-nitric oxide pathway: a target for new drugs.

PMID- 7508540
TI  - Seasonal variations of plasma fibrinogen and factor VII activity in the elderly:
      winter infections and death from cardiovascular disease.
AB  - There are approximately 20,000 excess deaths from cardiovascular disease each
      winter in England and Wales. The reasons for the excess have not been fully
      elucidated. For one year, we studied 96 men and women aged 65-74 living in their
      own homes in order to examine seasonal variation in plasma fibrinogen and factor
      VII clotting activity (FVIIc), and to investigate relationships with infection
      and other cardiovascular-disease risk factors. Both fibrinogen and FVIIc plasma
      values were greater in winter with estimated winter-summer differences
      (confidence intervals) of 0.13 (0.05-0.20) g/L for fibrinogen and 4.2 (1.2-7.1)%
      of standard for FVIIc. These differences could account for 15% and 9% increases
      in ischaemic heart disease risk in winter respectively. After adjustment for
      confounding by season, fibrinogen was strongly related to neutrophil count (p <
      0.0001), C-reactive protein (p < 0.0001), alpha 1-antichymotrypsin (p < 0.0001),
      and self-reported cough (p < 0.0001) and coryza (p = 0.0004), but not to ambient
      temperature. Therefore, we suggest that seasonal variation in fibrinogen might be
      induced by winter respiratory infections via activation of the acute phase
      response. Seasonal variations in the cardiovascular risk factors fibrinogen and
      FVIIc provide further possible explanations for the marked seasonal variation in
      death from ischaemic heart disease and stroke in the elderly.

PMID- 7508541
TI  - Risperidone.

PMID- 7508543
TI  - Varicella-zoster vaccine.

PMID- 7508542
TI  - Transmission electron microscopy and scanning probe microscopy.

PMID- 7508544
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. The subtlety of alkylating agents in reactions with biological
      macromolecules.
AB  - Genotoxic agents known to modify DNA by alkylation reactions (alkylating agents,
      AAs), either directly or after metabolic conversion to ultimately reactive
      intermediates, by no means represent a homogeneous class. For instance, their
      effectiveness for genotoxic damage, when expressed as the number of events (e.g.,
      mutations) per unit exposure dose, varies over a more than 1-million-fold range
      in dose. Despite the multiplicity of chemical and biological processes involved
      between DNA adduct formation and expression of genotoxic damage, the principal
      aims of studies on structure-activity relationships (SARs) are to (a) dissect the
      multi-step process of genetic damage formation into its most essential
      components, (b) use SARs for making predictions and, at a later step (c) as a
      basis for regulatory measures. The analytical tools available for such a
      comprehensive analysis in eukaryotic systems include determination of multiple
      genetic endpoints: molecular mutation spectra, relative clastogenicity
      (clastogenic events in relation to forward mutation induction) and the
      quantitative measure of enhanced mutagenicity in repair-deficient conditions. The
      genetic activity profiles obtained in this way can then be compared with
      fundamental physico-chemical properties of the AAs under consideration (such as
      Swain-Scott's s value, a useful indicator of the selectivity of an AA in its
      reactions with nucleophiles of distinct nucleophilic strength n in DNA, RNA and
      proteins), their functionality (monofunctional versus cross-linking) and their
      tumorigenic potency (TD50s compared with measures of initial DNA interaction,
      i.e., O6-/N7-alkylguanine ratios, s values or the covalent binding index
      determined in the liver in vivo). The combination of these different methods
      revealed that carcinogenic potencies of AAs in rodents vary over a 10,000-fold
      range in dose, with the extremes having the following characteristics: (i)
      Chemicals of a relatively "high carcinogenic potency", as indicated by a low TD50
      in rodents, either have low nucleophilic selectivity (and therefore mainly act
      through O-alkylation in DNA) or are capable of cross-linking DNA. The
      monofunctional members of this group, typified by N-ethyl-N-nitrosourea, are
      active in both spermatogonia and post-spermatogonial stages in the mouse and in
      Drosophila. Cross-linking agents also have a low TD50 value in rodents but are
      expected generally not to display genetic action in premeiotic stages (exceptions
      mitomycin C and chlorambucil). (ii) A relatively low carcinogenic potential is
      associated with AAs of high Swain-Scott s values, typified by trimethyl
      phosphate, epichlorohydrin or methyl methanesulphonate.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7508545
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Two million rodent carcinogens? The role of SAR and QSAR in their
      detection.
AB  - The accurate prediction of chemical carcinogenicity can only be achieved by a
      balanced consideration of the following factors: the chemistry and metabolism of
      the test agent, the interaction between toxicity and genetic toxicity, the
      possibility of non-genotoxic events that trigger subsequent non-targeted
      mutagenesis, the difference between activities observed in vitro and in vivo, and
      the possible inadequacy and/or partiality of all datasets and observations.
      Extrapolation of activities within a series of congeners is usually possible, but
      predictions across different chemical classes/mechanisms of carcinogenicity are
      difficult. Artificial intelligence systems can be used to predict one or more of
      the above parameters given adequate learning sets, but the hope for a single,
      coherent and self-contained method of predicting all instances of carcinogenicity
      is unreal. The future of carcinogen/mutagen prediction lies with data-rich
      artificial intelligence systems based on known mechanistic principles used
      selectively within the context of chemical and biological human insight. The
      major current obstacle to progress is the assumption that mutagenicity and
      carcinogenicity are unitary phenomena that can be learned and predicted by
      artificial intelligence systems operating in isolation.

PMID- 7508546
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Approaches to SAR in carcinogenesis and mutagenesis. Prediction of
      carcinogenicity/mutagenicity using MULTI-CASE.
AB  - The assumptions and considerations underlying the use of structure-activity
      studies in the field of genotoxicity are discussed and reviewed. The MULTI-CASE
      program, recently introduced as a second generation CASE program is described and
      its special features highlighted. Some of the problems relevant to the use of
      structure-activity tools are also discussed. A list of these problems is as
      follows: Problems with non-congeneric data bases, Problems with expert systems,
      Problems with the size of the data bases, Problems with "structural alerts",
      Problems with QSAR, Problems with Metabolic transformations, and Problems with
      short-term assays.

PMID- 7508547
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Use of SAR in computer-assisted prediction of carcinogenicity and
      mutagenicity of chemicals by the TOPKAT program.

PMID- 7508548
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. The importance of the hydrophobic interaction in the mutagenicity of
      organic compounds.
AB  - The derivation of new QSAR and the review of published QSAR for the mutagenicity
      of a variety of chemicals acting on a variety of bacterial systems uncovers two
      classes of equations. 12 examples include a term for hydrophobicity and of these
      12, 11 require activation either by S9 or cytosolic enzymes for the reduction of
      nitro compounds. There are 4 examples of direct-acting mutagens which do not
      require activation. Of these 4, 3 do not contain a term for hydrophobicity. The
      odd example is that of the sulfonate esters which do not require activation, but
      contain a term in log P. The hydrophobicity factor is not correlated with the
      type of bacteria used for the test.

PMID- 7508549
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Application of SAR methods to non-congeneric data bases associated
      with carcinogenicity and mutagenicity: issues and approaches.
AB  - In both industry and government, structure-activity relationships (SAR) are
      capable of playing an important decision-support role in estimating the potential
      mutagenicity or carcinogenicity of chemicals for which bioassay test results are
      unavailable. Traditional SAR modeling approaches, however, are usually restricted
      to the consideration of structurally similar chemical congeners. The highly
      structurally diverse nature of current carcinogenicity and mutagenicity data
      bases has motivated development of more general SAR approaches, potentially
      applicable to the treatment of diverse, non-congeneric mutagenicity and
      carcinogenicity data bases. Three specific approaches are considered in some
      detail--Ashby's structural alerts model, classified as a "rule-based" SAR
      approach, and the computerized CASE fragment-based method and TOPKAT linear
      discriminant equation method, both classified as "correlative" SAR approaches.
      Relative strengths and limitations, and a number of common features and important
      distinctions between these 3 methods are discussed. Rule-base methods are highly
      flexible and able to incorporate many different types of relevant information,
      yet are biased towards current knowledge, viewpoints, and mechanistic
      assumptions, that may or may not hold true. Correlative SAR methods are less
      biased and offer the promise of "discovering" potentially new SAR associations
      that could lend fresh insight into the basis for a structure-activity
      association. However, problems associated with their application to non
      congeneric data bases relate to: modeling multiple or overlapping mechanisms of
      action with a single relationship; defining the range of applicability of models
      in complex multi-dimensional structure-activity space; assigning confidence
      levels to predictions in the absence of knowledge concerning mechanisms of
      activity; and determining the potential mechanistic significance of diverse model
      parameters. It is argued that many of these concerns can be partially alleviated
      by careful application of statistical procedures, scrutiny of model results, and
      establishment of reasoned limits to the range of model applicability. The most
      significant confidence-building measure, however, will be a rationalization of
      the correlative SAR model and model parameters in terms of principles of chemical
      reactivity and postulated molecular mechanism(s) for the biological activity.
      Hence, it is recommended that models and model descriptors be designed to
      facilitate mechanistic interpretation and hypothesis generation. Finally,
      problems in comparing the relative predictive capabilities of different SAR
      approaches are discussed, and strategies for SAR investigation involving
      integration of existing techniques are suggested.

PMID- 7508550
TI  - Structural implications of the ICPEMC method for quantifying genotoxicity data.
AB  - Committee 1 of ICPEMC (International Commission for Protection against
      Environmental Mutagens and Carcinogens) devised a weight-of-evidence scheme for
      ranking chemicals with respect to their probability of inducing genetic effects.
      The score is based upon a hierarchical scheme which combines the results of many
      assays and assigns relative levels of relevance depending upon the phylogenic
      level of the assay, the nature of the genetic endpoint and the dose of chemical
      required. Analysis of the ICPEMC data base of quantitative genotoxicity scores by
      CASE and MULTICASE, two structure-activity relational expert systems, revealed
      that the ICPEMC quantitative classification "made sense" structurally, i.e. there
      was internal consistency with respect to the structural determinants associated
      with the qualitative as well as the quantitative classifications. Analysis of
      subsets of in vitro and in vivo genotoxicity results revealed that there was
      almost a complete overlap among the structural determinants associated with the
      qualitative classifications [i.e. likelihood of having a positive or negative
      score] of chemicals but that there were significant differences among the
      determinants related to the quantitative in vitro and in vivo scores (i.e.
      potency). Overall, the analyses suggest that there is a continuum in the
      structural bases of genetic effects which span phyla.

PMID- 7508551
TI  - In vitro genotoxicity studies of chrysotile asbestos fibers dispersed in
      simulated pulmonary surfactant.
AB  - Micronucleus (MN) formation and sister-chromatid exchange (SCE) assays were
      performed for asbestos in cultured Chinese hamster lung (V79) cells to determine
      the effect of surfactant treatment on the genotoxicity of two chrysotile asbestos
      samples of different fiber lengths. The cells were challenged in vitro with NIEHS
      intermediate- and short-length chrysotile fibers in both their native state and
      with surfactant pretreatment. For the surfactant pretreatment, the fibers were
      incubated in a simulated pulmonary surfactant which was prepared by
      ultrasonically dispersing dipalmitoyl lecithin (DPL), a primary component of
      pulmonary surfactant, in minimal essential medium (MEM). Chrysotile asbestos was
      ultrasonically mixed into the prepared surfactant dispersion or into MEM. V79
      cells were exposed to DPL-treated intermediate-length chrysotile (TICA),
      intermediate-length chrysotile (ICA), DPL-treated short-length chrysotile (TSCA)
      or short-length chrysotile (SCA) fibers for 48 h. For each treatment, 2000
      mononucleated cells were scored for MN formation, and 30 M2 metaphase cells were
      scored for SCE induction. The results showed that all samples, TICA, ICA, TSCA
      and SCA, caused significant elevation in the frequency of cells with micronuclei
      and of cells with two or more nuclei. The increase in micronucleus frequency was
      greatest in cells challenged with untreated intermediate-length fibers, and was
      greater for untreated than for DPL-treated short-length fibers. For the short
      length fiber samples, DPL surfactant treatment decreased activity for multiple
      nucleus formation, while DPL treatment did not result in consistent changes in
      that activity for intermediate-length fibers. Results of SCE assays were either
      negative or inconclusive. Cells were more viable following TICA and TSCA than
      following ICA and SCA challenge as measured by cell counts after 48 h of
      incubation.

PMID- 7508552
TI  - Mutagenicity of mild gasification products in Salmonella typhimurium.
AB  - Mild gasification is a coal-conversion technology that is currently under
      development in order to help meet future energy needs. 7 products from this
      process were assayed for mutagenic activity in the pre-incubation variant of the
      Salmonella assay (Ames test) using both DMSO and Tween 80 as sample solvents.
      Significant mutagenic activity was detected only in the wide-boiling-point
      composite materials, and the amount of this activity was found to be dependent on
      the solvent utilized. The highest number of revertants detected were on TA98 and
      its O-acetyltransferase over-producing derivative, YG1024, in the presence of the
      S9 microsomal fraction. Aromatic amines were suggested as a possible source of
      the mutagenic activity elicited. An examination of the liquid and tar phases of
      one composite material (MG-120) indicated that the mutagenic activity was
      restricted to the tar phase.

PMID- 7508553
TI  - Mutagenic activity of 3 industrial chemicals in a battery of in vitro and in vivo
      tests.
AB  - 3 chemicals were selected for mutagenicity testing from a priority list, based on
      production volume and available mutagenicity data. Propargyl alcohol (PA), 2
      nitroaniline (2NA), and 5-methyl-1H-benzo-triazole (MBT) were selected for
      testing using the approach recommended in the Health Protection Branch
      Genotoxicity Guidelines. The battery of tests included the Salmonella/mammalian
      microsome mutation assay, the in vitro chromosomal aberration assay, and the bone
      marrow micronucleus assay. The results indicate that 2 of the 3 chemicals, PA and
      2NA, were clastogenic in vitro. Both PA and 2NA induced chromosomal aberrations
      in CHO cells in vitro with and without metabolic activation, while none induced
      reverse mutations detectable with the Salmonella/mammalian microsome assay.
      Because PA and 2NA were found to be in vitro clastogens, they also were tested in
      the mouse bone-marrow micronucleus assay. 2NA induced a small increase in
      micronuclei in males but not females. PA did not induce an increase in
      micronuclei.

PMID- 7508554
TI  - Induction of chromosome aberrations and micronuclei in pulmonary alveolar
      macrophages of rats following inhalation of mosquito coil smoke.
AB  - The genotoxic potential of inhalation of mosquito coil (MC) smoke was evaluated
      by using metaphase chromosome aberration and micronucleus assays in pulmonary
      alveolar macrophages (PAMs) of rats following short-term as well as long-term
      whole body intermittent exposure. For short-term exposure, the animals were
      exposed for 15 min/h, 8 h/day to smoke collected for 1, 5 or 10 min, and they
      were killed 16 or 24 h after the final exposure. For long-term exposure, they
      were exposed for 15 min/h, 8 h/day, 7 days/week to smoke collected for 10 min and
      then they were killed 24 h after the final exposure. Each time before exposure,
      fresh smoke was collected by burning a mosquito coil. Pulmonary lavage was
      collected, and conventional flame-drying preparation was done for metaphase
      chromosome analysis and micronuclei (MN) were analyzed from smear preparations.
      Significantly higher frequencies of chromosome aberrations, including as well as
      excluding gaps, and micronucleated PAMs in smoke-exposed animals, compared to
      controls, indicated genotoxic capacity of MC smoke. The increases significantly
      correlated with the "concentration" of the gas. Mitotic indices also showed a
      significant and concentration-dependent increase. The frequencies of chromosome
      aberrations and MN following 7-day exposure were very similar to those for 1-day
      exposure. This was probably due to the transient nature of PAMs. A post-exposure
      gap of 24 h, compared to the 16-h gap, yielded a higher incidence of both mitoses
      and chromosome aberrations.

PMID- 7508555
TI  - Evaluation of the yeast DEL assay with 10 compounds selected by the International
      Program on Chemical Safety for the evaluation of short-term tests for
      carcinogens.
AB  - The Saccharomyces cerevisiae DEL assay detects a wide variety of nonmutagenic
      carcinogens (Schiestl et al. (1989) Carcinogenesis, 10, 1445-1455). This study
      shows the effect on DEL recombination of 8 carcinogenic compounds (o-toluidine,
      hexamethylphosphoramide, safrole, acrylonitrile, benzene, diethylhexylphthalate,
      phenobarbital and diethylstilbestrol) and 2 noncarcinogenic compounds
      (caprolactam and benzoin). These chemicals have been selected by the Program on
      Chemical Safety for the evaluation of short-term tests for carcinogens, because
      sufficient carcinogenicity data for these compounds exist, and because they are
      difficult to detect with the Salmonella assay. 5 of 8 carcinogens reproducibly
      gave a strong positive response and the noncarcinogen benzoin was negative. Thus,
      60% of the chemicals tested in this study have been correctly identified with the
      DEL assay compared to only 20% with the Salmonella assay.

PMID- 7508556
TI  - Cytogenetic effects of the antichagasic benznidazole on human cells in vitro.
AB  - Benznidazole (bz) is a widely used trypanosomicidal agent in South America. Two
      test systems were used to evaluate its genotoxicity in human cells in vitro: (a)
      human blood lymphocytes from healthy volunteers for induction of sister-chromatid
      exchanges (SCEs) and chromosomal aberrations (CAs); (b) a human hepatoma cell
      line (Hep G2) for the induction of SCEs and micronuclei (MN). In spite of being
      non-clastogenic on human lymphocytes, there was a significant increase in the
      frequency of MN on hepatoma cells treated with different doses of bz. This
      results support previous data which indicated the necessity of nitroreduction of
      nitroimidazoles to observe their mutagenic effects. Interestingly, bz induced a
      significant increase in the frequency of SCEs in both test systems. The
      sensitivity of the parameters used and the role of cellular metabolic pathways
      are discussed.

PMID- 7508557
TI  - Detection of 1,2,4-benzenetriol induced aneuploidy and microtubule disruption by
      fluorescence in situ hybridization and immunocytochemistry.
AB  - Fluorescence in situ hybridization (FISH) is becoming increasingly used to detect
      chromosomal changes in cancer cytogenetics. Here, we report its use in human HL60
      cells to detect aneuploidy induced by the benzene metabolite, 1,2,4-benzenetriol
      (BT). Human centromeric probes specific for chromosomes 9 and 7 were used.
      Untreated HL60 cells were 0.72 +/- 0.29% hyperdiploid for chromosome 9. Treatment
      with 5 microM BT increased this level 3-fold to 2.20 +/- 0.87% and 50 microM
      increased it 4-fold to 2.96 +/- 0.74%. Similar results were obtained with the
      chromosome 7 probe. The induction of aneuploidy by BT is therefore not chromosome
      specific nor is it artifactual. Immunocytochemical staining with anti-tubulin
      antibodies also showed that BT disrupted microtubule organization at these
      concentrations. Thus, mitotic spindle disruption probably plays an important role
      in BT-induced aneuploidy. Trisomy and not tetrasomy accounted for the majority of
      the hyperdiploidy induced by BT in the two C-group chromosomes 7 and 9. Since
      trisomy of C-group chromosomes is commonly observed in leukemia, BT-induced
      aneuploidy may be involved in benzene-induced leukemia.

PMID- 7508558
TI  - In vivo effect of chlorophyllin on gamma-ray-induced sister chromatid exchange in
      murine bone marrow cells.
AB  - The aim of the present work is to determine the radioprotective capacity of
      chlorophyllin, by measuring the reduction of gamma-ray-induced sister-chromatid
      exchange (SCE) in murine bone marrow cells in vivo. The results obtained in two
      separate experiments, using 10, 50 and 100 micrograms of chlorophyllin per g of
      body weight (bw), indicate that chlorophyllin per se did not have any effect on
      the SCE frequency and that the dose of 100 micrograms/g bw protects 100% against
      the induction of SCE by 1.0 Gy of gamma-rays; 50 micrograms/g bw protects less
      than 50% and 10 micrograms/g bw affords no protection.

PMID- 7508559
TI  - Comparative investigation of anticlastogenic effects in cell cultures of healthy
      donors and patients with nettle-rash.
AB  - In cultures of lymphocytes from 12 healthy donors and 12 patients with nettle
      rash (NR) the anticlastogenic effect of the antimutagens WR-2721 (WR), bemitil
      (BM), tomerzol (TM) and interferon (IF) on the induction of chromosomal
      aberrations by photrin (PT) and dioxidine (DX) was investigated. There were no
      statistically significant differences between healthy donors and patients with NR
      in the levels of chromosomal aberrations that were spontaneous or induced by PT
      or DX. Statistically significant protective effects of BM, WR, TM and IF were
      demonstrated in cells of healthy donors after treatment with PT or DX, and after
      modification of the clastogenic action of PT in lymphocytes of NR patients. There
      was no protective effect of any of the anticlastogens after treatment of the
      lymphocyte cultures from NR patients with DX. That observation allows us to
      suggest the test of anticlastogenic action as a measure of sensitivity of the
      chromosomal apparatus in groups with different genetic risks.

PMID- 7508560
TI  - Disturbed centromeric meiotic pairing leads to chromosome breaks.
AB  - In Drosophila females an extended deletion of the second autosome pericentric
      heterochromatin Df(2R) M-S2-10 under heterozygous conditions results in the loss
      of autosome 2, formation of autosomal compounds and stable acrocentric
      chromosomes (free arms). The presence of an inversion in the opposite chromosome
      suppresses the clastogenic effect of the deletion. This effect is presumed to be
      due to the formation of the conjugational loop in the region of pericentric
      heterochromatin which subsequently breaks.

PMID- 7508561
TI  - Comparative mouse micronucleus evaluation in bone marrow and spleen using
      immunofluorescence and Wright's Giemsa.
AB  - Bone marrow and spleen toxicity, clastogenicity and aneugenicity were analyzed in
      the CD1 mouse using an antikinetochore antibody (AKA) procedure (Krishna et al.,
      Mutation Res., 282, 159-169, 1992). Further, to verify the fluorescence
      micronucleus (MN) analysis, additional slides were stained with Wright's Giemsa
      and results were compared. 5 mice per sex were treated with cyclophosphamide (CP)
      (40 mg/kg) or vincristine (VC) (0.1 or 0.2 mg/kg). Slides were prepared 24 h
      postdose using a column fractionation procedure. Per animal, 400 total
      erythrocytes (TEs) for toxicity and 2000 polychromatic erythrocytes (PCEs) for MN
      per tissue were analyzed. In the fluorescent method, the clastogen, CP, produced
      MNPCEs predominantly devoid of kinetochores (K) and the aneugen, VC, produced
      mostly MNPCEs containing K. The MNPCE frequency did not differ significantly
      between tissues; however, it differed statistically between sexes. On an overall
      basis, spleen had significantly lower PCE to TE ratios compared to bone marrow.
      In general, CP and VC caused a small, but statistically significant decrease in
      PCE frequencies compared to controls, suggesting possible toxicity to these
      tissues at the given doses. The data on Wright's stain indicated that the
      proportion of PCEs and MNPCEs in general, were comparable to those using
      fluorescent stain. This study further confirms the usefulness of an AKA-staining
      technique in a multiple genetic endpoint evaluation under a single set of
      microscopic conditions.

PMID- 7508562
TI  - Mutational spectrum of chromium(VI) in human cells.
AB  - The mutational spectrum of K2Cr2O7 on the low melting domain within exon 3 of
      hypoxanthine guanine phosphoribosyl transferase (hprt) gene was obtained from 6
      thioguanine-resistant (6TGr) human lymphoblasts (TK6). Using a combination of
      high-fidelity polymerase chain reaction (PCR) and denaturing gradient gel
      electrophoresis (DGGE), we found four chromium(VI) induced hotspots in a 104-bp
      target sequence. The hotspots were C:G-->A:T at bp 243, representing 4.5% of 6TGr
      mutants; A:T-->T:A at bp 247 (2.0%); G:C-->A:T at bp 289 (2.5%) and C:G-->T:A at
      bp 312 (4.0%). Mutational hotspots at bp 243 have previously been determined for
      hydrogen peroxide (C:G-->G:C) and benzo[a]pyrene diol epoxide (C:G-->A:T). Two of
      the hotspots, bp 243 and 289, arose in a common quadruplet 5'-ACAT-3' in the
      untranscribed and transcribed strands respectively.

PMID- 7508563
TI  - Antioxidative and antimutagenic effects of theaflavins from black tea.
AB  - Theaflavins, polyphenolic ingredients of black tea, were observed to inhibit in
      vitro lipid peroxidation in the erythrocyte membrane ghost and microsomal
      systems. Theaflavins also showed inhibition of DNA single-strand cleavage and
      mutagenicity, both induced by hydrogen peroxide. These results suggest that
      theaflavins scavenge radicals to produce antioxidative and antimutagenic effects.
      It was also found that the gallic acid moiety of theaflavins is essential for
      their potent antioxidative activities.

PMID- 7508564
TI  - Mutation spectrum of a binary mixture of mutagens (methapyrilene and sodium
      azide) in strain TA1535 of Salmonella.
AB  - Methapyrilene (MP) is a rat-liver carcinogen and cocarcinogen that exhibits a
      narrow spectrum of mutagenic activity in Salmonella typhimurium, inducing only a
      2-fold increase in revertants only in the base-substitution strain TA1535; it
      also enhances the mutagenic activity of sodium azide (NaN3) in the same strain.
      To examine the effects of MP at the molecular level, we used the colony probe
      hybridization procedure developed by Cebula and Koch (Mutation Res., 229 (1990)
      79-87) to identify the base substitutions in approximately 800 background, MP-,
      NaN3-, and MP + NaN3-induced revertants of the hisG46 allele of strain TA1535.
      The predominant mutation in all 4 mutation spectra was a CCC-->CTC transition.
      The results suggest a mechanism by which MP enhances the infidelity of the DNA
      replication complex or inhibits a DNA repair or proofreading function, resulting
      in the production of more of the same error that occurs normally and that is also
      induced by NaN3. Such a mechanism might be the basis for the carcinogenic and
      cocarcinogenic activities of MP. To our knowledge, this is the first report of
      the molecular analysis of mutants produced by exposure of cells to a binary
      mixture of mutagens.

PMID- 7508565
TI  - Germ-cell mutagenicity of etoposide: induction of meiotic micronuclei in cultured
      rat seminiferous tubules.
AB  - Mutagen effects on male germ cells can be quantified by meiotic micronucleus
      induction in vitro. Late pachytene and diakinetic spermatocytes are able to
      differentiate through meiotic divisions in vitro and develop to round spermatids.
      In the presence of mutagens micronucleus induction reflects the potential of the
      chemical to induce chromosome breakage or uneven chromosome distribution. In this
      study we have investigated the mutagenicity of etoposide (VP-16) and its ability
      to induce micronuclei S-independently in meiosis by the meiotic micronucleus
      method in vitro. Our results indicate that etoposide is able to cause a
      statistically significant increase in the frequency of micronuclei at a
      concentration range as low as 0.5-8 mu mole/l. The meiotic micronucleus method in
      vitro seems to be a feasible and sensitive test system of male germ-cell
      mutagenesis.

PMID- 7508566
TI  - Functional complementation of the radiation-sensitive mutant M10 cell line by
      human chromosome 5.
AB  - The mouse lymphoma (L5178Y) cell mutant M10 is defective in rejoining DNA double
      strand breaks and is hypersensitive to ionizing radiation. The introduction of
      human chromosome 5 into M10 cells by microcell mediated chromosome transfer
      complemented the ionizing-radiation hypersensitivity defect of this cell line.
      The presence of chromosome 5 in the microcell hybrids was shown using PCR with
      chromosome-specific primers and fluorescence in situ hybridization. From this
      data we conclude that the gene that corrects the radiation hypersensitivity of
      M10 cells is located on chromosome 5 and tentatively assigned to the 5q14 to
      5pter region. We designate this gene XRCC4L.

PMID- 7508567
TI  - Relative biological effectiveness and dose rate effect of tritiated water on
      chromosomes in human lymphocytes and bone marrow cells.
AB  - Tritiated water (HTO) is a major toxic effluent from the nuclear power industry,
      that is released into the environment in large quantities. The low dose radiation
      effect and dose rate effect of HTO on human lymphocytes and bone marrow cells
      have not been well studied. The present study was therefore undertaken to
      investigate the HTO dose-response relationship for chromosomal aberrations in
      human lymphocytes and bone marrow cells at low in vitro radiation doses ranging
      from 0.1 to 1 Gy. Lymphocytes (G0 stage) and bone marrow cells were incubated for
      10-150 min with HTO at a dose rate of 2 cGy/min (555 MBq/ml). The relative
      biological effectiveness (RBE) of HTO was calculated with respect to 60Co gamma
      rays for the induction of dicentric and centric ring chromosomes at low radiation
      doses. The RBE value for HTO beta-rays relative to 60Co gamma-rays was 2.7 for
      lymphocytes and 3.1 for chromatid aberrations in bone marrow cells. Lymphocytes
      were also chronically exposed to HTO for 6.7-80 h at dose rates of 0.5 cGy/min
      (138.5 MBq/ml) and 0.02 cGy/min (5.6 MBq/ml). There was a 71.5% decrease in the
      yield of dicentrics and centric rings at the dose rate of 0.02 cGy/min,
      indicating a clear dose rate effect of HTO. The RBE value for HTO relative to
      137Cs gamma-rays was 2.0 at a dose rate of 0.02 cGy/min, suggesting that low HTO
      dose rates produce no increase of the RBE values and that the values may be
      constant between 2 and 3 within these dose rates. These results should prove
      useful in assessment of the health risk for humans exposed to low levels of HTO.

PMID- 7508568
TI  - Influence of the processing of MucA protein on the reversion of the frameshift
      hisD3052 and the base substitution hisG46 mutations by chemical mutagens in
      Salmonella typhimurium.
AB  - The correlation between the proficiency at promoting mutagenesis of MucA/B
      proteins and MucA processing has been considered to be very high (Hauser et al.,
      1992) on the basis of the results of UV mutagenicity (Shiba et al., 1990). Here
      we show that this correlation is only partial. We have assayed the mutagenicity
      of benzo[a]pyrene (B[a]P) and aflatoxin B1 (AFB1) in Salmonella typhimurium
      tester strains containing plasmids which encode MucA proteins with an altered
      cleavage site. Reversion of the frameshift hisD3052 mutation by B[a]P or AFB1 was
      observed in the presence of non-cleavable MucA protein although at a lower level
      than that found in cells containing wild-type MucA protein. Reversion of the base
      substitution hisG46 mutation by AFB1 requires a significant processing of MucA,
      while lower levels of this processing would be enough for the hisG46 reversion by
      B[a]P. These results suggest that the specificity of mutations induced by
      mutagens forming DNA adducts is influenced by the activity of MucA protein. They
      also show the relevance of mutagenicity assays in the mechanistic studies of
      mutagenesis.

PMID- 7508569
TI  - The clastogenic and mutagenic effects of ascorbigen and 1'-methylascorbigen.
AB  - Ascorbigen, which occurs naturally in the human diet, and a synthetic analogue
      (1'-methylascorbigen), were assayed for cytotoxic and clastogenic activities in a
      SV40-transformed Indian Muntjac cell line (SVM), and for mutagenic activity in
      the Ames test using Salmonella typhimurium strains TA98 and TA100. Ascorbigen had
      no effect upon the clonal survival of SVM at concentrations below 0.21 mg/ml and
      did not induce either chromosome aberrations or sister-chromatid exchanges (SCEs)
      at any concentration tested up to the maximum compatible with the assay
      conditions; nor did it induce mutations in either Salmonella strain. In contrast,
      1'-methylascorbigen was an order of magnitude more cytotoxic, demonstrating a Dq
      of 0.03 mg/ml, and whilst it too was not found to induce chromosome aberrations
      it did induce SCEs in SVM (although only at highly cytotoxic doses) and mutations
      in the Ames test.

PMID- 7508570
TI  - Analysis of multiaberrant cells in lymphocytes of persons living in different
      ecological regions.
AB  - An analysis was carried out of multiaberrant ("rogue") cells in lymphocytes of
      persons living in unpolluted areas (controls), and in areas chemically or
      radioactively (Chernobyl fall-out) polluted. The total number of analysed cells
      was 102,391, among these 10 cells with three and more aberrations were found.
      These multiaberrant cells occur in persons of both sexes and various ages living
      in regions with a moderate degree of mutagenic exposure. The main types of
      aberrations in multiaberrant cells were chromosome exchanges, accompanied by
      double fragments.

PMID- 7508571
TI  - No correlation between DNA strand breaks and HPRT mutation induced by
      photochemical treatment in V79 cells.
AB  - DNA strand breaks, measured by alkaline elution, and hypoxanthine guanine
      phosphoribosyltransferase (HPRT) mutation were studied in V79 cells after
      photochemical treatment (PCT) or exposure to X-rays. Cells were incubated with
      the photosensitizers Photofrin II (PII) and three closely related porphyrins
      tetra-(3-hydroxyphenyl) porphyrin (3THPP), meso-tetra-(4-sulfonatophenyl)
      porphine (TPPS4) and meso-tetra-(N-methyl-4-pyridyl) porphine (TMPyPH2). These
      dyes are assumed to act on cellular targets mainly via singlet oxygen when
      excited by light. While the hydrophilic TPPS4 and TMPyPH2 did not photoinduce
      mutants to any significant extent, both lipophilic dyes, 3THPP and PII, were
      significantly mutagenic when excited by light. On the other hand, TPPS4 was the
      most efficient sensitizer of alkali-labile DNA strand breaks, while TMPyPH2 did
      not induce any significant amount of either type of DNA damage. Surprisingly, no
      correlation between the two parameters was found for PCT, either after exposures
      inactivating 50% of the cells or after exposures inactivating 90% of them. The
      lack of correlation between the yields of DNA strand breaks and of mutants could
      not be explained by differences in the intracellular localization pattern of the
      dyes.

PMID- 7508572
TI  - Spermatid micronucleus analyses of trichloroethylene and chloral hydrate effects
      in mice.
AB  - Mice were exposed by inhalation to trichloroethylene (TCE) or by i.p. injection
      to the TCE metabolite, chloral hydrate (CH). Early spermatids were analyzed for
      micronucleus (MN) frequency and the presence or absence of kinetochore(s) using
      fluorochrome-labeled anti-kinetochore antibodies. It was determined that 5
      consecutive days of exposure to 5, 50 or 500 ppm TCE during preleptotene through
      early pachytene stages of meiotic cell development do not result in increased
      frequencies of spermatid MN. CH at 41, 83 or 165 mg/kg was positive for spermatid
      MN induction when treatments corresponded to spermatogonial stem cell or
      preleptotene spermatocyte stages of development; negative results were obtained
      after treatments of leptotene-zygotene or diakinesis-metaphase stages. The
      significantly increased levels of MN observed were invariably of the kinetochore
      negative type.

PMID- 7508573
TI  - Evaluation of potential mutagenic effect of the liquid smoke preparation UTP in
      vivo: cytogenetic analysis of mouse bone marrow.
AB  - The effect of the liquid smoke preparation (UTP) on chromosomes of mouse bone
      marrow cells was evaluated by cytogenetic analysis. UTP was administered to male
      and female mice in four concentrations: 100, 10, 1 and 0.1 ml UTP/1000 ml of
      drinking water continuously during 4 weeks ad libitum. The UTP concentrations
      used did not show any mutagenic effect under these testing conditions.

PMID- 7508574
TI  - Memory impairment and neural dysfunction after continuous infusion of anti-nerve
      growth factor antibody into the septum in adult rats.
AB  - Nerve growth factor is required for the survival and maintenance of cholinergic
      neurons in the central nervous system. The direct infusion into the rat's septum
      of an anti-nerve growth factor monoclonal antibody, which inhibits nerve growth
      factor bioactivity seven times more strongly than a polyclonal antibody, caused
      very severe damage to the hippocampal cholinergic system. Anti-nerve growth
      factor polyclonal antibody also neutralized endogenously occurring nerve growth
      factor. The infusion of anti-nerve growth factor polyclonal antibody produced a
      dysfunction of memory and decreased choline acetyltransferase activity and
      acetylcholinesterase staining in the hippocampus. The cholinergic dysfunction and
      impairment of memory recovered to the normal level two weeks after cessation of
      the infusion of the anti-nerve growth factor polyclonal antibody. These results
      suggest that a deficit of nerve growth factor in the adult brain causes neuronal
      dysfunction.

PMID- 7508575
TI  - Monitoring of cyclic GMP during cerebellar microdialysis in freely-moving rats as
      an index of nitric oxide synthase activity.
AB  - The nitric oxide synthase/cyclic GMP pathway has been studied in vivo in the
      adult rat cerebellum by monitoring the levels of extracellular cyclic GMP during
      microdialysis in conscious unrestrained animals. The basal cyclic GMP efflux was
      concentration-dependently reduced upon local infusion of the nitric oxide
      synthase inhibitor NG-nitro-L-arginine (10 microM-1 mM). The nitric oxide donor S
      nitroso-N-penicillamine, perfused through the dialysis probe at 1 mM, increased
      by about 200% the extracellular levels of cyclic GMP. The glutamate receptor
      agonist N-methyl-D-aspartate (500 microM) produced a cyclic GMP response which
      was abolished by the selective receptor antagonist D-2-amino-5-phosphonovaleric
      acid (500 microM) or by NG-nitro-L-arginine (10 microM). The elevation of cyclic
      GMP levels caused by local infusion of 500 microM N-methyl-D-aspartate was also
      abolished by parenteral administration of the N-methyl-D-aspartate channel
      blocker dizocilpine (0.4 mg/kg, i.p.). Local perfusion of the phosphodiesterase
      inhibitor 3-isobutyl-1-methylxanthine (1 mM) increased by about 150% the
      extracellular levels of cyclic GMP. It is concluded that cyclic GMP collected
      during in vivo microdialysis reflects nitric oxide synthase activity in the rat
      cerebellum. The technique may be utilized to investigate the pathophysiology and
      the pharmacology of the nitric oxide/cyclic GMP pathway in the cerebellum of
      living animals.

PMID- 7508576
TI  - NADPH-diaphorase (nitric oxide synthase)-reactive amacrine cells of rabbit
      retina: putative target cells and stimulation by light.
AB  - In the mammalian retina there are two populations of nitric oxide synthase
      containing amacrine cells that stain with the nicotinamide adenine dinucleotide
      phosphate-diaphorase reaction. To determine the response of these neurons to
      light, immunoreactivity to Fos proteins was used as a marker of synaptic
      activation. Fos immunoreactivity is absent in dark-adapted retinas, but 70% of
      large, Type I nicotinamide adenine dinucleotide phosphate-diaphorase-reactive
      amacrine cells and 5-10% of the smaller but more numerous Type II nicotinamide
      adenine dinucleotide phosphate-diaphorase-reactive amacrine cells contain Fos
      proteins after light stimulation. To localize putative cellular targets of nitric
      oxide in the retina, retinas were stained immunocytochemically for cyclic GMP
      after the local administration of the nitric oxide donors sodium nitroprusside
      and S-nitroso-N-acetylpenicillamine. Both compounds induce strong cyclic GMP
      immunoreactivity in ON cone bipolar cells. The data suggest that the light
      induced inward current in ON cone bipolar cells is enhanced by a nitric oxide
      cyclic GMP pathway and that the major source of nitric oxide is the nicotinamide
      adenine dinucleotide phosphate-diaphorase-reactive amacrine cells in the rabbit
      retina.

PMID- 7508577
TI  - Pituitary adenylate cyclase activating peptide is a sensory neuropeptide:
      immunocytochemical and immunochemical evidence.
AB  - Pituitary adenylate cyclase activating peptide (PACAP) is a vasoactive intestinal
      peptide-like hypothalamic peptide occurring as two variants, PACAP-27 and the C
      terminally extended PACAP-38. Immunoreactive PACAP has also been demonstrated in
      the enteric nervous system and in the innervation of the respiratory tract. We
      have examined the possibility that PACAP occurs in the sensory nervous system of
      the rat. Immunocytochemistry revealed PACAP in numerous nerve fibres in the
      superficial layer of the dorsal horns of the spinal cord, in nerve cell bodies
      (most of them of small size) of the spinal ganglia and trigeminal ganglia and in
      nerve fibres running close to and within the surface epithelium in the skin of
      the nose, the tongue, the larynx-trachea, and the urinary bladder as well as
      around the ducts of the submandibular gland. In all locations, PACAP co-existed
      with calcitonin gene-related peptide and substance P, the PACAP-immunoreactive
      fibres and cell bodies constituting a subpopulation of those storing substance P
      and/or calcitonin gene-related peptide. Additional PACAP-immunoreactive fibres
      not associated with epithelia seemed to lack calcitonin gene-related peptide and
      substance P. Capsaicin treatment reduced the density of PACAP- and calcitonin
      gene-related peptide/substance P-immunoreactive fibres in the tissues examined.
      On the whole, the immunocytochemical results agreed with those obtained by
      radioimmunoassay for PACAP and CGRP. The data favour a role for PACAP in primary
      sensory neurons.

PMID- 7508578
TI  - Relative contribution of sympathetic and sensory nerves to thermal nociception
      and tissue trophism in rats.
AB  - Neonatal injection of 6-hydroxydopamine (420 mg/kg s.c.) lowered thermal
      nociceptive threshold (hot plate and tail immersion tests) and increased levels
      of substance P-like immunoreactivity in the skin (paws, tail, area of vibrissae)
      of Wistar rats. Chemical ablation of primary afferents, induced in either
      neonatal or adult rats by systemic administration of capsaicin, increased thermal
      nociceptive threshold (hot plate), irrespective of 6-hydroxydopamine
      pretreatment, and reduced substance P-like immunoreactivity in the hind-paw skin
      of either control or sympathectomized rats. Capsaicin pretreatment of neonatal
      but not adult rats produced antinociceptive effect in the tail-immersion test and
      completely reversed the hyperalgesic effect of sympathectomy, without affecting
      levels of substance P-like immunoreactivity in the tail skin. These findings
      indicate that sympathetic nerves and different subsets of capsaicin-sensitive
      primary afferents are involved in the processing of thermal nociceptive input.
      Corneal and cutaneous lesions were induced by neonatal sensory denervation with
      capsaicin. Sympathectomy afforded protection against the development of corneal
      pathology, while it did not affect the occurrence of cutaneous lesions. It
      appears that a balance in the neuronal activity between sympathetic neurons and
      trigeminal sensory neurons is critical for maintaining the normal trophism of the
      cornea, and that sensory neuropeptides play a key role in the maintenance of
      normal trophism of the skin.

PMID- 7508579
TI  - Distribution and co-localization of 5-hydroxytryptamine, thyrotropin-releasing
      hormone and substance P in the cat medulla.
AB  - This study demonstrates the co-existence of three neurochemicals in ventral
      medullary neurons of the cat utilizing fluorescence immunohistochemistry. Neurons
      containing 5-hydroxytryptamine, thyrotropin-releasing hormone and substance P
      were identified within the rostrocaudal extent of the medulla, specifically
      within the raphe pallidus and raphe magnus and in the reticular formation of the
      ventrolateral medulla in the nucleus paragigantocellularis lateralis. Within the
      raphe pallidus the majority of 5-hydroxytryptamine-containing neurons were co
      localized with thyrotropin-releasing hormone and substance P. However, in the
      raphe magnus the majority of stained neurons contained 5-hydroxytryptamine and
      thyrotropin-releasing hormone but were devoid of substance P. In the
      ventrolateral medulla two major populations of neurons were identified rostral to
      the inferior olivary nuclei, one containing 5-hydroxytryptamine and thyrotropin
      releasing hormone, while a more lateral group contained substance P alone. More
      caudally, at the level of the inferior olives, the majority of 5
      hydroxytryptamine-containing cells also displayed immunoreactivity for
      thyrotropin-releasing hormone and substance P. A consistent finding in both the
      ventromedial and ventrolateral regions of the medulla was a population of 5
      hydroxytryptamine-containing cells which did not stain for either thyrotropin
      releasing hormone or substance P. The functional role of co-localized
      neurochemicals remains unknown but co-existence of neurotransmitter substances in
      medullary neurons may allow for specific and multiple actions in the spinal cord.

PMID- 7508580
TI  - Synergistic action of estradiol and myelin basic protein on mast cell secretion
      and brain myelin changes resembling early stages of demyelination.
AB  - Mast cells are known for their participation in immediate and, more recently,
      delayed hypersensitivity reactions. They have been found in the meninges and
      certain brain areas where they are strictly perivascular, in close apposition to
      neurons, and they are activated by direct nerve stimulation or by neuropeptides.
      Intracranial mast cells contain many vasoactive substances which can increase the
      permeability of the blood-brain barrier, proteolytic enzymes which can degrade
      myelin in vitro, as well as chemotactic molecules which can attract inflammatory
      molecules in vivo. Connective tissue mast cells, with which intracranial mast
      cells share many characteristics, contain cytokines which can cause inflammation
      directly. Multiple sclerosis is a human demyelinating disease of unknown
      etiology, with a high prevalence in women which results in penetration of blood
      borne immune cells within the brain parenchyma and subsequent destruction of
      myelin. Here, we report that 17 beta-estradiol and myelin basic protein, a major
      suspected immunogen in multiple sclerosis, had a synergistic action on inducing
      mast cell secretion. This effect was more pronounced in Lewis rats, which are
      susceptible to the development of experimental allergic encephalomyelitis, an
      animal model for multiple sclerosis, than in Sprague-Dawley rats, which are
      fairly resistant. Moreover, 18 h incubation of purified peritoneal mast cells
      with homogeneic slices of brain white matter in the presence of 17 beta-estradiol
      and myelin basic protein resulted in myelin changes resembling early stages of
      brain demyelination, which were also more evident in Lewis rats than in Sprague
      Dawley rats. These results support the notion that mast cells could participate
      in the pathophysiology of demyelinating diseases.

PMID- 7508581
TI  - Prominent location of a K+ channel containing the alpha subunit Kv 1.2 in the
      basket cell nerve terminals of rat cerebellum.
AB  - A panel of monoclonal antibodies specific for a family of voltage-dependent, fast
      activating K+ channels, raised against alpha-dendrotoxin acceptors purified from
      bovine brain, were used to probe the distribution of these important proteins in
      rat cerebellum. All the antibodies reacted with their antigens in the folial
      white matter, the granular cell layer and the basket cell nerve termini within
      the Purkinje cell layer. However, a very intense staining pattern was exhibited
      by only one monoclonal that reacts exclusively with Kv 1.2 alpha subunit, the
      predominant isoform present in alpha-dendrotoxin sensitive K+ channels. Double
      labelling procedures with neuronal and glial markers were used to verify this
      discrete antibody staining of the basket cell terminals that synapse with the
      base of Purkinje cell bodies in a readily recognizable and characteristic
      fashion. This is the first direct demonstration, using a monoclonal antibody, of
      a presynaptic location for a voltage-activated K+ channel; its discrete
      distribution in the basket cell pinceau suggests that it could control release of
      the inhibitory transmitter GABA and, thereby, influence excitability of Purkinje
      cells in the cerebellum.

PMID- 7508582
TI  - GABA and enkephalin projection from the nucleus accumbens and ventral pallidum to
      the ventral tegmental area.
AB  - GABAergic and enkephalinergic afferents to the ventral tegmental area were
      investigated in the rat using retrograde tracing techniques combined with in situ
      hybridization. Following iontophoretic deposit of Fluoro-Gold in the ventral
      tegmental area labeling in the forebrain was most dense in the shell of the
      nucleus accumbens, rostral ventromedial ventral pallidum and diagonal band of
      Broca. A smaller density was also observed in the lateral septum. In these
      forebrain regions, the portion of retrogradely labeled cells that contained mRNA
      for glutamate decarboxylase ranged from 25% to 50%, whereas only 5% to 15% were
      double-labeled for preproenkephalin mRNA. Cells double-labeled with either
      glutamate decarboxylase or preproenkephalin mRNA were most numerous in the
      lateral septum, shell of the nucleus accumbens, rostral ventral pallidum and
      diagonal band of Broca. Large Fluoro-Gold deposits which invaded the medial
      substantia nigra resulted in a significant number of retrogradely labeled cells
      in the core of the nucleus accumbens, and a portion of these neurons also
      contained mRNA for glutamate decarboxylase or preproenkephalin. These data
      demonstrate the presence of GABAergic and enkephalinergic neurons projecting from
      the nucleus accumbens, ventral pallidum and diagonal band of Broca to the ventral
      tegmental area.

PMID- 7508583
TI  - Monoarthritis in the rat knee induces bilateral and time-dependent changes in
      substance P and calcitonin gene-related peptide immunoreactivity in the spinal
      cord.
AB  - Bilateral changes in the spinal cord and dorsal root ganglion content of the
      sensory peptides substance P and calcitonin gene-related peptide have been
      previously reported in animal models of arthritis which affect many joints within
      the body. The central nervous system has been implicated in the symmetry of joint
      involvement in human rheumatoid arthritis. We aimed to determine whether
      unilateral inflammation of the knee joint can also induce bilateral changes in
      the spinal cord. We have induced a monoarthritis in the knee joint of the rat and
      used quantitative immunocytochemistry to look at changes of these peptides in the
      dorsal horn of the spinal cord and the dorsal root ganglia. Furthermore we have
      examined the responses during the acute (three days) and the chronic (21 days)
      phases of the model. The data show that in the acute phase of the monoarthritis
      there is both an ipsilateral and contralateral response which increases the
      immunoreactive substance P and calcitonin gene-related peptide in the L4 level of
      the dorsal horn of the spinal cord. In the chronic phase of the monoarthritis,
      the contralateral side of the dorsal horn returned to control values whilst the
      ipsilateral side showed reduced amounts of immunoreactive substance P and
      calcitonin gene-related peptide compared to controls. We propose that the acute
      response, at three days, to unilateral inflammation is appropriate and has
      evolved to protect an organism against the original insult ipsilaterally, and the
      possibility of subsequent insult contralaterally.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508584
TI  - Distribution of immunoreactivity for enkephalin, substance P and vasoactive
      intestinal peptide in fibres surrounding splanchnic sympathetic preganglionic
      neurons in rats.
AB  - The distribution of substance P, enkephalin and vasoactive intestinal peptide in
      fibres and cells was examined in the autonomic nuclei of the lower thoracic and
      lumbar segments of the rat spinal cord. Attention was focussed on the location of
      the peptides in sympathetic preganglionic neurons contributing to the greater and
      lesser splanchnic nerves and in fibres surrounding these neurons. To identify
      splanchnic preganglionic neurons, Fluoro-Gold was applied to the left splanchnic
      nerve in anaesthetized rats and some of these animals received intrathecal
      administration of colchicine at thoracic segments 6, 9 and 12, 24-48 h before
      perfusion with fixative. Immunoreactivity for substance P, enkephalin and
      vasoactive intestinal peptide in fibres and cells of the sixth thoracic to second
      lumbar spinal cord was detected with fluorescent immunocytochemical techniques.
      Most retrogradely labelled cells (90%) were located in the intermediolateral
      nucleus and the rest were situated in the nucleus intercalatus and the central
      autonomic nucleus of the gray matter. Terminals of fibres containing
      immunoreactivity to all three peptides were found in all autonomic regions.
      Fibres immunoreactive for substance P and enkephalin were seen projecting in the
      white matter to the region of the intermediolateral nucleus and extending from
      this nucleus to the central autonomic nucleus. Terminals containing each of the
      three peptides were also found surrounding the retrogradely labelled cells in the
      intermediolateral nucleus. Approximately two cells immunoreactive for vasoactive
      intestinal peptide were found per section and 80% were located in the autonomic
      regions. Fewer cells immunoreactive for substance P and enkephalin were observed
      (approximately one per section) and 70% were outside laminae VII and X. Although
      cells immunoreactive for substance P, enkephalin and vasoactive intestinal
      peptide were located in all autonomic regions of the spinal cord, cells doubly
      labelled with retrograde dye and with the antisera to either of the peptides
      could not be identified. The data suggest that (i) substance P, enkephalin and
      vasoactive intestinal peptide are contained in fibres of neurons regulating
      preganglionic sympathetic control of the abdominal viscera and its vasculature;
      and (ii) these peptides may not be major transmitters within splanchnic
      preganglionic neurons.

PMID- 7508585
TI  - N-methyl-D-aspartate-induced nitric oxide release: an in vivo microdialysis
      study.
AB  - Increasing evidence indicates that nitric oxide acts as an intercellular signal
      transduction molecule in the nervous system. In particular, in vitro studies have
      demonstrated that nitric oxide is produced in the cerebellar cortex and is
      responsible for the increases in cyclic GMP seen in response to glutamate
      receptor activation. In this study, we have combined the technique of
      intracerebellar microdialysis with a sensitive assay for nitric oxide oxidation
      products nitrate and nitrite, to assess nitric oxide release directly in awake,
      freely moving animals. We have found that infusion of N-methyl-D-aspartate via
      the microdialysis probe results in a dose-dependent increase in cerebellar nitric
      oxide release. This increase was prevented by prior administration of an N-methyl
      D-aspartate receptor antagonist, or the nitric oxide synthase inhibitor NG
      nitroarginine. Both these pretreatments also reduced the basal extracellular
      nitrite and nitrate levels, suggesting that there is a tonic glutamate-induced
      nitric oxide production in the cerebellum of awake, freely moving animals. These
      results provide direct evidence for nitric oxide release in response to N-methyl
      D-aspartate receptor activation in the adult cerebellar cortex, in vivo. This new
      approach, coupling microdialysis with the azo dye detection method of Griess,
      should thus prove useful for the in vivo study of nitric oxide release from
      various brain regions in response to pharmacological, physiological or behavioral
      manipulations.

PMID- 7508586
TI  - The sensitivity of hippocampal long-term potentiation to nitric oxide synthase
      inhibitors is dependent upon the pattern of conditioning stimulation.
AB  - Inhibition of nitric oxide synthase prior to conditioning has been previously
      found to reduce levels of hippocampal long-term potentiation. In the present
      experiments in the rat, the reduction of long-term potentiation by nitric oxide
      synthase inhibitors was highly conditioning-dependent. We have characterized the
      relative importance of the number of conditioning stimulus trains, pulse number,
      intensity, and pattern in the reduction of long-term potentiation by nitric oxide
      synthase inhibitors. Long-term potentiation was reduced relative to control
      values only when multiple conditioning stimulus trains were presented at maximal
      stimulus intensity; potentiation produced by an equivalent number and intensity
      of stimuli presented in a single conditioning train was not reduced by nitric
      oxide synthase inhibitors, and multiple-train-induced potentiation was sensitive
      to nitric oxide synthase inhibitors only when maximal stimulation intensity was
      employed. Another form of synaptic potentiation, primed-burst potentiation, was
      reduced by nitric oxide synthase inhibition, while homosynaptic and
      heterosynaptic depression were unaffected. Our results support the hypothesis
      that conditioning-dependent release of nitric oxide can contribute to long-term
      potentiation, but also show that its blockade by nitric oxide synthase inhibitors
      is dependent on the nature of the conditioning stimulus, and that long-term
      potentiation can be generated that is apparently resistant to the effects of
      these drugs.

PMID- 7508587
TI  - Monoclonal antibody G10 which recognises microtubule-associated protein 1x
      identifies growing axons of neurons microtransplanted into adult rat hippocampus.
AB  - Monoclonal antibody G10 recognises an epitope on microtubule-associated protein
      1x, a developmentally regulated cytoskeletal protein expressed in immature axons
      of the central and peripheral nervous systems. Here we report that G10 can be
      used to identify the axonal projections of syngeneic embryonic (E14-E15)
      hippocampal cells microtransplanted by a minimally traumatic technique into
      intact adult host hippocampus.

PMID- 7508588
TI  - Chemosensitivity of C-cells in bullfrog dorsal root ganglia to substance P and
      adenosine 5'-triphosphate.
AB  - Dissociated bullfrog dorsal root ganglion cells were voltage clamped in the whole
      cell configuration. In small C-cells having 20 microns as averaged diameter,
      substance-P (0.1-1 microM) inhibited an M-type potassium current while ATP (1-10
      microM) activated a sodium-potassium current. In large A-cells (approximately 65
      microns in diameter) in which ATP has been shown to inhibit M-current, substance
      P (0.1-1 microM) also inhibited this potassium current without activating the
      sodium-potassium current. Results provided evidence for the distinction between A
      and C-cells in terms of their chemosensitivity.

PMID- 7508589
TI  - Subcellular distribution and immunological detection of retrograde axonally
      transported proteins in acrylamide and diabetic neuropathies.
AB  - Neuropathies produced by both acrylamide- and streptozotocin-induced diabetes in
      the rat are accompanied by a deficit in the retrograde axonal transport of a
      defined group of proteins that can be visualized on two-dimensional
      polyacrylamide gels. In this work, these proteins are identified as being
      primarily soluble and being absent from rat brain. They are not immunologically
      related to the major retrogradely transported protein synaptophysin. Polyclonal
      antiserum to the proteins was produced in mice and used to confirm the reduction
      in their retrograde transport in sciatic nerve of diabetic and acrylamide-treated
      rats.

PMID- 7508590
TI  - [Oily contrast medium used for chemoembolization in the palliative treatment of
      extensive inoperable primary hepatocellular carcinomas].
AB  - Transcatheter arterial oily chemoembolization using cytostatics mixed with
      lymphographic contrast agent with or without Gelfoam embolization seems currently
      to be the most suitable treatment for unresectable hepatocellular carcinomas
      (HCC). 5 patients with inoperable, biopsy proven huge HCC (average size 404 cm2)
      were treated by multiple cycles (3-7, average 4.6 cycles) of a triple drug
      combination including doxorubicin, cisplatin and mitomycin-C together with
      Lipiodol. In 13/23 cycles the lipiodolization was complemented by Gelfoam
      embolization increasing the efficacy of treatment. The hypervascular HCC-s showed
      marked reduction in size (degree of regression was 33-66%, average 55%). The
      median follow-up was 1918 (13-36 months). Three patients are still alive with
      follow-up ranging from 15-36 months (average 23 months) despite the progression
      of the disease. One patient died of tumorous cachexia 13 months after initial
      treatment, while another one, who developed partial remission, lost his life in a
      road accident 17 months after his first cycle.

PMID- 7508592
TI  - Effects of colchicine applied to the peripheral nerve on the thermal hyperalgesia
      evoked with chronic nerve constriction.
AB  - Loose ligatures placed unilaterally on the sciatic nerve results in a thermal
      hyperalgesia. We applied 5 or 50 mM colchicine (COL, blocker of the fast axonal
      transport) to the sciatic nerve and examined the effects of COL on thermal
      hyperalgesia and the levels of substance P (sP), calcitonin gene-related peptide
      (CGRP) and vasoactive intestinal polypeptide (VIP) in the spinal cord and the
      sciatic nerve. These data showed that the application of 50 mM COL to the sciatic
      nerve in this study functioned as an axonal transport blocker. COL abolished the
      hyperalgesic state in a concentration-dependent manner when applied proximal to
      the constriction injury. COL (50 mM), when applied distal to the injury, had no
      effect on the hyperalgesia. COL did not alter motor function or paw withdrawal
      response in the non-lesioned animal. Examination of peptide levels in nerve shows
      that COL resulted in an accumulation of sP, CGRP and VIP in the nerve. In the
      dorsal horn, COL resulted in a modest reduction in levels of sP and CGRP as
      compared to the non-lesioned side while VIP levels were elevated. These data
      suggest that active factors generated by the focal nerve compression and carried
      by fast axonal transport from the lesioned site to the spinal cord and/or dorsal
      ganglion are important in the development of thermal hyperalgesia after
      constriction injury in rats.

PMID- 7508591
TI  - Behavioral characterization of the excitatory and desensitizing effects of
      intravesical capsaicin and resiniferatoxin in the rat.
AB  - This study characterized the excitatory (nociceptive) and desensitizing
      (antinociceptive) properties of the natural pungent substances, capsaicin (CAP)
      and resiniferatoxin (RTX) instilled in the bladder (intravesical, i.ves.) via an
      indwelling cannula in awake, freely moving rats. The incidence of 9 behaviors was
      scored for 10 min following i.ves. vehicle or RTX (1.0 nmol). Abdominal licking
      and head-turning occurred significantly more often in RTX-treated rats compared
      to vehicle controls, whereas head-grooming, locomotion, rearing and biting did
      not differ between the two groups. Little or no vocalization, defecation or
      hindlimb hyperextension was observed in either RTX- or vehicle-treated rats. A
      second injection of either vehicle or RTX administered to RTX-treated rats 60 min
      later did not significantly increase abdominal licking or head-turning compared
      to vehicle controls; this subsequent lack of excitation was taken as a measure of
      desensitization. In a separate experiment, the first injection of i.ves. RTX (0.1
      3.0 nmol) increased licking in a dose-dependent manner; in contrast, the first
      injection of i.ves. CAP (0.1-3.0 mumol) significantly increased licking only at
      the intermediate dose tested, 1.0 mumol. With each subsequent injection of the
      same drug and dose at 30-min intervals, licking increased to a lesser extent,
      such that it was not significantly different from control after the fourth
      injection. Rats treated with i.ves. CAP or RTX also did not show increased
      licking when administered the opposite treatment 30 min later (RTX or CAP,
      respectively), indicating cross-desensitization; however, i.ves. administration
      of a third, higher dose of RTX reinstated licking behavior in these
      'desensitized' rats. Subcutaneous administration of CAP (18-180 mg/kg) or RTX (18
      180 micrograms/kg) dose-dependently attenuated the excitatory response to i.ves.
      CAP and RTX administered 2 days later. Whereas rats treated systemically with RTX
      also were desensitized to the excitatory effects of RTX instilled in the eye
      (evaluated in the eye-wipe assay), rats treated i.ves. with RTX and vehicle
      treated rats showed a normal eye-wiping response. Finally, pretreatment with
      i.ves. ruthenium red, a cation channel blocker, antagonized the excitatory and
      desensitizing effects of i.ves. RTX. This study demonstrates that repeated
      application of both CAP and RTX into the bladder produces behavioral effects
      indicative of local sensory afferent desensitization. I.ves. CAP and RTX appear
      to produce their excitatory and desensitizing effects via a common mechanism,
      which is dependent on cation channel activation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7508594
TI  - Some remarks on the growth-rate and angiogenesis of microvessels in ischemic
      stroke. Morphometric and immunocytochemical studies.
AB  - Variability in microvessel changes of blood vessel density has prompted us to
      undertake quantitative morphometric studies of infarcted areas in human brain. In
      the initial study, brains were obtained at autopsy from 10 patients (ages 45-85).
      Samples were collected from infarcted hemisphere and controls from the
      contralateral hemisphere. Formalin fixed, paraffin embedded and thereafter
      routinely processed sections were stained after Pickworth and with HE. Altogether
      6,520 microvessels, representing 10,801 microscopic fields were counted. The
      Wilcoxon Range test was used for statistical analysis. In 9 of 10 patients in
      infarcted brain hemispheres, there was a marked increase in microvessel density
      (p < 0.01), when compared with contralateral brain hemisphere. In addition, a
      positive correlation was also found between the time of survival and both total
      density and density of non-perfused blood vessels. To gain a deep insight into
      the enhanced activity of microvessels, immunocytochemical studies were performed,
      which have shown, that the vascular endothelial cells in infarcted brain were
      reactive to two monoclonal antibodies, one, E-9, directed against an
      activation/proliferation associated endothelial cell specific protein and the
      other recognizing adhesion molecule VCAM-1. Pan-endothelial Mab PECAM/CD31 was
      used in those studies for controls and confirmed the obtained results. Our
      findings strongly support the concept of angiogenesis in the infarcted area. If
      correlated with morphometric results, it may indicate an important role of
      microvessels in pathobiology of ischemic stroke.

PMID- 7508593
TI  - [Contribution of cytokines to inflammatory mechanisms].
AB  - A large number of cytokines are found within foci of inflammation. Two of these
      cytokines, namely interleukin-1 (IL-1) and tumor necrosis factor (TNF), play a
      key role in orchestrating the mechanisms responsible for inflammation. These two
      cytokines induce production by many cells of lipid mediators, proteases, and free
      radicals, all of which play a direct role in development of the deleterious
      effects of inflammation. IL-1 and/or TNF exert cytotoxic effects on the vascular
      endothelium, cartilage, bone, muscle, or pancreatic beta-cell islets. Cytokines,
      including interferon gamma (IFN), IL-3 and granulocyte-macrophage colony
      stimulating factor (GM-CSF), amplify the inflammatory response by increasing
      production of IL-1 and TNF by macrophages. Macrophages also produce other
      cytokines, such as IL-8 and macrophage chemoattractant protein-1 (MCP-1), with
      chemoattractant properties that contribute to draw leucocytes to the site of
      inflammation. IL-6, produced in large amounts during inflammatory processes,
      induces the production of acute phase proteins by hepatocytes. IL-1, TNF, IL-11,
      leukemia inhibitory factor (LIF), and transforming growth factor beta (TGF beta)
      share this effect. TGF beta also has a number of anti-inflammatory effects. TGF
      beta, IL-4, and IL-10 inhibit production of IL-1 and TNF. Glucocorticoids also
      have this effect. Glucocorticoids can be produced as a result of a chain of
      events initiated by IL-1, TNF, and IL-6 and involving the neuro-endocrine axis.
      Other substances, such as IL-1 receptor antagonist (IL-1 ra) or soluble forms of
      the TNF receptors, can specifically inhibit the effects of IL-1 and TNF. Cascade
      production of cytokines, inhibition, negative feed-back, and synergistic
      mechanisms are parameters that illustrate the concept of "cytokine network" and
      aptly characterize the role of these mediators in the mechanisms of inflammation.

PMID- 7508595
TI  - Influence of dextrans on platelet distribution in arterioles and venules.
AB  - Dextrans bind to the surface of platelets, red blood cells and endothelium. We
      investigated whether a low doses (30 mg/kg IV) of 40-kDa (Dx40), neutral, 500-kDa
      (Dx500) or sulphated, 500-kDa (Dx500S) dextrans influence platelet distribution
      in rabbit mesenteric arterioles and venules (diameter 17-33 microns). Intravital
      fluorescence videomicroscopy was used to visualize platelets labelled in vivo
      with acridine red. Their concentration distribution determined within a thin
      optical section about the median vessel plane was expressed relative to the mean
      concentration in that vessel. In arterioles, Dx500 and Dx500S increased the
      relative platelet concentration in the centre [radial position (R): 0.0-0.4 R]
      from 0.60 to 1.07 (P < 0.001) and 1.20 (P < 0.003), and reduced it near the wall
      (0.8-0.9 R) from 1.59 to 0.93 (P < 0.02) and 0.95 (P < 0.03) respectively. In
      venules a similar, but non-significant, effect was observed. Dx40 did not change
      platelet distribution in arterioles, but decreased their concentration in venules
      in the centre from 1.08 to 0.71 (P < 0.03) and increased it at the wall from 0.89
      to 1.27 (P < 0.04). The deformability of red blood cells was unchanged, but their
      aggregation tendency increased approximately two-fold after Dx500 and Dx500S
      injection, while Dx40 had no influence. Leucocyte margination in venules did not
      affect platelet distribution. Dextran injection did not change microvascular flow
      velocity or plasma viscosity, suggesting that the observed changes in arteriolar
      platelet distribution were caused by binding of dextran to the surface of
      platelets and/or red blood cells.

PMID- 7508597
TI  - The use of transcranial Doppler in the hemodynamic assessment of implanted
      pacemakers.
AB  - Twenty patients with DDD pacemakers had their intracranial cerebral circulation
      assessed in different pacing modes, using transcranial Doppler. The studies were
      performed at the vertebral artery in a sitting position. Although DDD pacing was
      preferred to VVI pacing in 18 of the 20 patients, the figures did not reach
      statistical significance. There was no statistical difference in maximal blood
      flow velocity between DDD pacing at 60 and 80 beats/min. Varying the AV interval
      from 150-250 msec also demonstrated no clear difference in maximal peak Doppler
      velocity, in the group as a whole, though there was a greater individual
      preference for 150 msec. Transcranial Doppler assessment of the hemodynamics of
      the cerebral circulation is of limited value as an indicator of mode or rate
      preference in the pacemaker population.

PMID- 7508596
TI  - Properties of spontaneous inward currents in rabbit pulmonary artery smooth
      muscle cells.
AB  - Spontaneous inward and outward currents were studied with perforated patch
      recording in freshly dispersed rabbit pulmonary artery smooth muscle cells. With
      physiological potassium concentrations, spontaneous outward and inward currents
      were recorded at negative membrane potentials. Ion substitution experiments
      revealed that the outward and inward currents were respectively potassium and
      chloride conductance increases. Both conductances were abolished by bath
      application of caffeine (2-10 mM), which releases calcium from internal stores.
      The rise time and half-decay time of spontaneous potassium currents were both
      about 25 ms. The spontaneous chloride current has a rise time of 30 ms and
      decayed exponentially with a time constant (tau) of 70 ms at -50 mV. The tau
      value was increased by depolarization and increased e-fold for a change of 99 mV
      in membrane potential. In every cell examined when the spontaneous currents
      occurred as biphasic events, typically between -20 mV and -40 mV, outward
      currents preceded inward currents in over 90% of these events whereas the inward
      current always preceded the outward current in caffeine- and noradrenaline-evoked
      responses. An explanation for these data is that there may be localization of
      some chloride channels with respect to the caffeine-sensitive calcium store.

PMID- 7508598
TI  - Does atrial fibrillation cause false-positive late potentials?
AB  - We hypothesized that atrial fibrillation may cause false-positive late potentials
      due to the recording of baseline atrial activity. We performed signal-averaged
      ECGs in 26 patients with atrial fibrillation before and after conversion to
      normal sinus rhythm. Signal-averaged ECGs were recorded for > 200 cycles with a
      noise level of < or = 0.5 microV. The signals were band-pass filtered at 40-250
      Hz. We examined filtered QRS duration (fQRS), duration of low amplitude signal <
      40 microV (LAS), and the root mean square (RMS) of the terminal 40 msec of the
      QRS complex. A late potential was considered present when two of the following
      three criteria were met: fQRS > or = 114 msec, LAS > or = 38 msec, and RMS < or =
      20 microV. The mean +/- standard deviation of the fQRS in atrial fibrillation and
      sinus rhythm were 113 +/- 28 and 110 +/- 25 msec; of the LAS 38 +/- 17 and 37 +/-
      15 msec; of the RMS 27 +/- 22 and 28 +/- 21 microV; of the noise 0.25 +/- 0.08
      and 0.22 +/- 0.07 microV (P = NS). Ten signal-averaged ECGs in atrial
      fibrillation had late potentials. With reversion to sinus rhythm one of these 26
      patients gained a late potential; two others lost a late potential (P = NS by
      McNemar's Chi-square). There was no significant difference in the signal-averaged
      ECG parameters or noise levels. In conclusion, signal-averaged ECG parameters are
      not significantly changed by cardioversion of atrial fibrillation to normal sinus
      rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508600
TI  - Efficacy of type 1C antiarrhythmic agents for treatment of resistant atrial
      fibrillation.
AB  - In order to determine the efficacy of type 1C agents (flecainide, encainide,
      propafenone) in patients with atrial fibrillation who have failed to maintain
      sinus rhythm with type 1A agents (quinidine, procainamide, disopyramide), 147
      patients, that were admitted into the John Dempsey Hospital with new or recurrent
      atrial fibrillation between 1987-1991, were studied retrospectively. Out of the
      total, 29 patients converted spontaneously to sinus rhythm, 14 patients were left
      in atrial fibrillation, and 104 patients were given a type 1A antiarrhythmic.
      Sixty-five of these patients remained in sinus rhythm (54% converted on drug
      alone, 46% required electrical cardioversion) for at least 6 months. Of the
      remaining 39 patients, 28 were given a type 1C antiarrhythmic; 13 were
      successfully converted (61% chemical, 39% electrical) to and remained in sinus
      rhythm for at least 6 months; the remaining 15 either failed to convert or
      reverted to atrial fibrillation. New onset atrial fibrillation had a
      significantly lower incidence of congestive heart failure (10%) than recurrent
      atrial fibrillation (33%; P < 0.01). No differences in digoxin, beta blocker use,
      or other clinical characteristics were seen either between type 1A or type 1C
      successes or failures. Similarly, echocardiographic dimensions did not predict
      success or failure with either class of agent. In conclusion, type 1C
      antiarrhythmics for suppression of recurrent atrial fibrillation represent a
      reasonable therapeutic alternative for suppression of atrial fibrillation in
      patients who have failed type 1A agents. Prognostic factors predicting success or
      failure remain undetermined.

PMID- 7508599
TI  - Clinical experience with a new DDD external pacemaker.
AB  - A multicenter trial of a new external DDD pacemaker was conducted to evaluate its
      clinical performance. Additionally, methods of temporary lead implantation were
      analyzed for best performance. The device was found to function with few
      complications. In only 16 of the 146 devices used was the DDD mode abandoned. Of
      these, 3 were changed to the AAI mode and 4 were for atrial fibrillation. Several
      methods of lead implantation proved satisfactory. However, a simple U stitch
      through the muscle functioned best for atrial application and either a U stitch
      or a tined stitch functioned best for ventricular application.

PMID- 7508601
TI  - Can amiodarone pulmonary toxicity be predicted in patients undergoing implantable
      cardioverter defibrillator implantation?
AB  - Implantable cardioverter defibrillator (ICD) implantation is rapidly becoming
      accepted as primary therapy for malignant ventricular arrhythmias. Many patients
      undergoing ICD implantation are on concomitant antiarrhythmic drugs to decrease
      shock frequency, slow tachycardia rate, and suppress supraventricular
      arrhythmias. Amiodarone is a potent antiarrhythmic agent that is also frequently
      used in the treatment of patients with refractory ventricular arrhythmias. Ten to
      forty percent of patients undergoing ICD implantation will also be taking
      amiodarone. It has been reported to cause pulmonary toxicity in about 5% of
      patients per year. Acute amiodarone toxicity presenting as adult respiratory
      distress syndrome has been reported much less frequently. Although perioperative
      morbidity due to amiodarone has been described, the risk, predictability, and
      consequences of acute pulmonary toxicity from amiodarone in patients undergoing
      ICD implantation have not been previously described. We reviewed the records of
      99 consecutive patients undergoing ICD implantation at our institution from
      October 1987 to April 1992. Thirty-nine patients were taking 480 +/- 230 mg of
      amiodarone (median 400 mg, lower 20th percentile 400 mg, upper 80th percentile
      800 mg) for 291 +/- 554 days prior to ICD implantation. Ten patients taking
      amiodarone developed acute pulmonary toxicity clinically manifesting as diffuse
      pulmonary infiltrates on chest radiography and adult respiratory distress
      syndrome with hypoxia (arterial pO2 < 60 mmHg) without evidence of pneumonia or
      elevated pulmonary capillary wedge pressure (PCW < or = 15 mmHg). Of the 60
      patients not taking amiodarone none developed adult respiratory distress
      syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508602
TI  - Classification of death in patients under antiarrhythmic treatment.
AB  - In the evaluation of antiarrhythmic treatment, total mortality and total cardiac
      mortality are the only endpoints difficult to misclassify. End-stage cardiac
      failure competes with "suddenness" in many instances of sudden arrhythmic death.
      This observational study reports on 23 deaths in a group of 129 patients under
      antiarrhythmic treatment. In the 21 cases of cardiac death, with respect to the
      notion "sudden arrhythmic death," classification was problematic in 6 patients.
      According to different interpretations, the number of deaths listed as "sudden"
      could vary between one and six. A concise description of cause and circumstances
      of death, is presented.

PMID- 7508603
TI  - The importance of timing muscle contraction in dynamic cardiomyoplasty.
AB  - This acute dynamic cardiomyoplasty (CMP) study used ten dogs (weight range 21-32
      kg) and was designed to determine the importance of the train of stimuli
      initiation time when applied to the thoracodorsal nerve, which innervates the
      latissimus dorsi (LD) muscle that is wrapped around the ventricles. Using the P
      wave of the cardiac electrogram to trigger a special delay circuit, the stimulus
      train could be initiated from the apex of the R wave to any time throughout and
      at the end of the isovolumic period, signaled by opening of the aortic valve. The
      cardiac electrogram (which contained the R wave), left ventricular pressure
      (LVP), aortic flow velocity (AFV), beat-by-beat stroke volume (SV), femoral
      artery pressure, and the envelope of the stimulus train were recorded as the
      onset of the stimulus train was varied from the R wave to the end of the
      isovolumic period with a pumping ratio of one LD contraction for every seven
      ventricular contractions. In four dogs there was a pronounced increase in the
      augmentation in LVP, AFV, and SV when the stimulus train was initiated later than
      40 msec after the first peak of the R wave. In five dogs the augmentation in LVP,
      AFV, and SV was not as clearly apparent, although all of these dogs exhibited an
      optimal train delay. Data were not obtained on one dog due to an anomalous LD
      muscle blood supply. For all of the dogs, the optimum train delay from the R wave
      averaged 58 msec (range 40-80 msec). The average augmentation in SV was 26%
      (range 13%-45%). The same muscle-wrap tightness was used in all dogs. In one dog,
      the muscle-wrap tightness was varied, and by tightening the wrap the SV
      augmentation increased from 17% to 27%. For all dogs the range of augmentation in
      SV (13%-45%) perhaps represents variations in muscle-wrap tightness, which may be
      a major uncontrolled factor in dynamic CMP.

PMID- 7508604
TI  - Detection of ventricular tachycardia and fibrillation using coronary sinus blood
      temperature: a feasibility study.
AB  - This study investigated the potential of coronary sinus blood temperature to
      detect ventricular arrhythmias. A rapid-response, thermistor-tipped catheter
      placed in the coronary venous system of anesthetized dogs was used to record the
      blood temperature during periods of induced bradycardia, tachycardia, and
      ventricular fibrillation. A second catheter was used to measure blood temperature
      in the aortic arch during these same episodes. A pulsatile component of venous
      blood temperature, typically 40 m degrees C in amplitude, was well correlated
      with the cardiac cycle, while another, slightly larger, pulsatile component was
      well correlated with respiration. The cardiac component peaked during ventricular
      systole, and the respiratory component peaked during expiration. As compared with
      sinus rhythm, the cardiac signal diminished during bradycardia and tachycardia
      and nearly disappeared during asystole and ventricular fibrillation. The baseline
      component of venous blood temperature rose during periods of tachycardia and
      fibrillation, while respiration proved to be an important factor in the baseline
      temperatures. The presence of small, cyclic, thermal variations in the coronary
      venous system was verified, and the concept of measuring metabolic activity to
      assess ventricular function was substantiated. These studies show promise that
      this concept could be incorporated into medical devices that use these
      temperature signals for diagnosis of ventricular arrhythmias.

PMID- 7508605
TI  - Effect of steroid eluting versus conventional electrodes on propafenone induced
      rise in chronic ventricular pacing threshold.
AB  - The aim of this study was to evaluate chronic ventricular pacing threshold
      increase after oral propafenone therapy. Eighty-three patients affected by
      advanced atrioventricular block and sick sinus syndrome were studied at least 3
      months after pacemaker implantation, before and after oral propafenone therapy
      (450-900 mg/day based on body weight). The patients were subdivided into three
      groups according to the type of unipolar electrode that was implanted: group I
      (41 patients) Medtronic CapSure 4003, group II (30 patients) Medtronic Target Tip
      4011, and group III (12 patients) Osypka Vy screw-in lead. In all cases a
      Medtronic unipolar pacemaker was implanted: 30 Minix, 23 Activitrax, 14 Elite, 12
      Legend, and 4 Pasys. Propafenone blood level was measured in 75 patients 3-5
      hours after propafenone administration. The pacing autothreshold was measured at
      0.8 V, 1.6 V, and 2.5 V by reducing pulse width. At the three different outputs
      before and after propafenone, threshold increments were significantly lower in
      group I in comparison with group II and group III (propafenone ranging from <
      0.001 to < 0.05). No significant difference was found in pacing impedance or in
      propafenone plasma concentration in the three groups. Strength-duration curves
      were drawn for each group at baseline and after propafenone administration.
      Before propafenone, in group I, the knee was markedly shifted to the left and
      downward as compared to the classic curve, so that the steep part was
      predominant; in group II and group III this shift was progressively less
      evident.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508606
TI  - Alternating Wenckebach periods and allied arrhythmias.
AB  - Alternating Wenckebach periods (AWPs) are episodes of 2:1 block during which the
      PR, AH, or AV intervals of the conducted beats gradually increase until a greater
      degree of block ensues. Most episodes occur at the AV node, but some have also
      been reported in other structures. AWPs are usually attributed to multilevel
      block due to transverse (horizontal) dissociation. This assumption was initially
      based on a method in which the solutions to difficult electrocardiographic
      rhythms were arrived at by analysis and deduction based on the knowledge existing
      at that particular time. Subsequently, it was reinforced by information
      extrapolated from intracardiac recordings performed in patients with documented
      multilevel block in separate anatomical structures (atria, AV node, and His
      bundle), as well as from microelectrode studies and computer simulations.
      Although AWPs are frequently observed in clinical tracings, those occurring at
      the AV node are best categorized during incremental atrial stimulation because
      then they occupy a specific point in the wide spectrum of tachycardia dependent
      AV nodal conduction disturbances. In fact, the A:H ratios occurring in the
      episodes where the degree of block increases can be represented by "universal"
      mathematical formulas. However, in the clinical setting, drugs affecting the
      electrophysiology of the node can alter the pacing induced symmetry by producing
      additional differential effects on the various levels. The latter still requires
      further elucidation.

PMID- 7508607
TI  - Concepts of the compartmental analysis.

PMID- 7508608
TI  - Funding for cardiac pacing and defibrillators in Calgary: the Robin Hood
      philosophy.

PMID- 7508609
TI  - Arteriovenous fistula: a complication of cardiac pacemaker lead placement and its
      management with percutaneous embolization.
AB  - A right internal mammary artery to right brachiocephalic vein fistula was
      discovered following implantation of a permanent cardiac pacemaker. The fistula
      was closed via percutaneous embolization.

PMID- 7508610
TI  - Return to arc welding following defibrillator implantation.
AB  - A male arc welder who was fitted with an implantable defibrillator wished to
      return to his former employment. Device testing and ambient magnetic field
      measurements were performed at his place of work. During welding, artifacts were
      seen on the intracardiac electrogram but there was no resulting disturbance of
      sensing function. Measured field strengths were too low to result in device
      inactivation. The patient resumed his work without incident. This appears to be
      the first reported case of a patient with an implantable defibrillator returning
      to this "electrically hostile" environment following thorough screening.

PMID- 7508611
TI  - Radiofrequency catheter ablation of right ventricular outflow tract tachycardia
      late after complete repair of tetralogy of Fallot using the pace mapping
      technique.
AB  - While surgical repair of tetralogy of Fallot has improved the long-term outlook
      for this patient population, sudden death late after repair remains a problem.
      Ventricular tachycardia (VT) originating in the right ventricular outflow tract
      (RVOT) is a well described, clinically important finding following surgical
      repair of tetralogy and a number of investigators suggest that this VT plays a
      critical role in the etiology of sudden death. We report two patients with RVOT
      VT late after repair of tetralogy who underwent successful radiofrequency
      ablation of their tachycardia.

PMID- 7508612
TI  - Maleficent magnets and mangled megabytes.

PMID- 7508613
TI  - Remove the "tarnish from the golden route".

PMID- 7508614
TI  - Easily removable tabs on a lead connector provide a quick and simple means to
      identify lead connections.

PMID- 7508615
TI  - STIMAREC report.

PMID- 7508616
TI  - Permanent pacemaker lead extraction.

PMID- 7508617
TI  - Intravascular extraction of chronic pacemaker leads: efficacy and follow-up.
AB  - Extraction of chronic pacemaker leads has been recommended for infections,
      prevention of venous thrombosis, migration, and possible perforation. Success
      with constant traction techniques has been variable, and the cost and morbidity
      of open chest surgical procedures are prohibitive. Efficacy of a new system for
      lead extraction using intravascular techniques was analyzed. The system (Cook
      Pacemaker) uses a locking stylet, which is secured at the distal electrode by
      counterclockwise rotation to reinforce the lead and facilitate traction, and
      dilator sheaths that are used to free the lead from adhesions in the venous
      system. In a series of 56 patients (ages 19-88) who presented for lead extraction
      because of erosion (5), infection (14), lead replacement (35), or other (2), 86
      leads were extracted. Thirty-two were atrial leads and 54 ventricular; 23 had
      active fixation and 63 passive. Average duration of implant was 58 +/- 42 months
      (range 1-264). Eighty-four leads were totally removed and two partially removed.
      For these two leads, the distal tip was not removed; in both cases the locking
      stylet was not secured at the distal electrode due to obstruction within the
      lead. Two patients developed arm edema following the procedure, which resolved
      with elevation. One patient developed a subclavian thrombosis, which resolved
      with warfarin anticoagulation. Four patients have expired due to unrelated
      causes. In conclusion, this intravascular approach for extraction of chronic
      leads is effective, and the procedure is safe when performed by experienced
      personnel.

PMID- 7508618
TI  - The Dotter retriever and pigtail catheter: efficacy in extraction of chronic
      transvenous pacemaker leads.
AB  - Several techniques exist for percutaneous extraction of chronic pacemaker leads.
      To establish the efficacy of the Dotter retriever and pigtail catheter, we
      reviewed the removal of 59 endocardial pacemaker leads in 42 patients (mean age
      71 years). The mean duration of lead implantation was 44 months (range 1-169
      months). Thirty-two leads were withdrawn with simple traction alone, and five
      leads were abandoned when traction failed. The remaining 22 leads were
      manipulated with a Dotter retriever or pigtail catheter, or both. Twelve leads
      were dislodged from the endocardium with simple traction (10) or with traction
      transmitted through an entwining pigtail catheter (2), but they could not be
      fully withdrawn. Eleven of these leads (92%) were then successfully extracted
      with the Dotter retriever. Seven of the remaining 10 leads were successfully
      dislodged and removed by the Dotter retriever. Overall, 9 of 12 leads (75%) that
      could not be dislodged from the endocardium with simple traction were removed
      with a Dotter retriever or pigtail catheter, or both. Three patients in whom no
      catheter method worked required thoracotomy for removal of infected leads. No
      complications resulted from use of the Dotter retriever or pigtail catheter. We
      conclude that the Dotter retriever and pigtail catheter have moderate efficacy
      for dislodging chronic endocardial leads. Once mobilized, however, the leads can
      be withdrawn with great success with the Dotter retriever. Newer technology
      should not result in the abandonment of this proven technique.

PMID- 7508619
TI  - Surgical removal of infected transvenous pacemaker leads.
AB  - Infection, though uncommon, can be the most lethal of all potential complications
      following transvenous pacemaker implantation. Eradication of infection associated
      with pacemakers requires complete removal of all hardware, including inactive
      leads. Since 1972, 5,089 patients have had 8,508 pacemaker generators implanted
      at Montefiore Medical Center. There were 91 infections (1.06%); four of our
      patients required surgical removal. Nine additional patients were referred for
      surgical removal of infected transvenous pacemaker leads from other institutions.
      Surgical methods for removal included use of cardiopulmonary bypass or inflow
      occlusion. Surgery may be safely used in unstable or elderly patients and should
      not be reserved as a last resort. This article reviews our surgical experience
      removing infected pacemaker leads at Montefiore Medical Center.

PMID- 7508620
TI  - Prostate-specific antigen, p30, gamma-seminoprotein, and E1.

PMID- 7508621
TI  - Phase I trial of high-dose fosfestrol in hormone-refractory adenocarcinoma of the
      prostate.
AB  - Androgen deprivation displays the mean therapy of advanced stage prostatic
      cancer. The development of hormone-resistant disease leads to a fatal tumor
      progression. High-dose fosfestrol (diethylstilbestrol disphosphate) has been
      suggested to circumvent hormone resistance and to induce a direct cytotoxic
      effect. Twenty-one patients with hormone-refractory prostate cancer were enrolled
      in a phase I trial of continuous infusion of high, daily escalating dose of
      fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a
      starting dose of 1.5 g/d. The dose was increased daily in the same patient
      according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and
      5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major
      side effect occurred. There was neither hematological nor cardiovascular
      toxicity. The main dose-limiting toxicities were nausea/vomiting in 17 patients,
      edema in 2 patients, and more than 5% weight gain in 3 patients. The planned
      maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3
      additional patients, after infusion prolongation. Seven patients experienced a
      subjective improvement: Prostatic acid phosphatase and prostatic specific antigen
      decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested
      dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10
      days.

PMID- 7508622
TI  - Developmental estrogenization and prostatic neoplasia.
AB  - The association of estrogens with benign prostatic hyperplasia and prostatic
      cancer has been widely studied, but no conclusive evidence exists for a role of
      estrogens in prostatic disease. This paper reviews the literature and describes
      studies which have sought to show a correlation of estrogens and alterations in
      the prostates of humans and experimental animal models. Using the developmentally
      estrogenized mouse model, we propose an alternative role for estrogens as a
      predisposing factor for prostatic diseases: estrogen exposure during development
      may initiate cellular changes in the prostate which would require estrogens
      and/or androgens later in life for promotion to hyperplasia or neoplasia. Thus,
      the critical time for estrogen action would be during the development of the
      prostatic tissue. We further suggest that estrogen-sensitive cells may remain in
      the prostate and be more responsive to estrogens later in life or less responsive
      to the normal controlling mechanisms of prostatic growth.

PMID- 7508623
TI  - Responses to the antagonistic analog of LH-RH (SB-75, Cetrorelix) in patients
      with benign prostatic hyperplasia and prostatic cancer.
AB  - Among new highly potent antagonistic analogs of luteinizing hormone-releasing
      hormone (LH-RH), containing neutral hydrophilic D-ureidoalkyl amino acids such as
      D-Cit and D-Hci at position 6 and free of edematogenic and anaphylactoid
      reactions, Ac-D-Nal(2)1, D-Ph(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10 (LH-RH) (SB-75;
      Cetrorelix) was shown to be one of the most powerful. In this trial, we evaluated
      the response to 500 micrograms SB-75 given every 12 hr subcutaneously (sc) for 4
      weeks in 11 patients with benign prostatic hyperplasia (BPH), and 6 weeks in 6
      prostatic cancer patients (2 stage C, 4 stage D2). In patients with BPH
      presenting with prostatism and urinary outflow obstruction, there was a
      noticeable clinical improvement after the first week of SB-75 administration.
      This improvement continued during the course of treatment. Before therapy with SB
      75, the serum levels of prostate-specific antigen (PSA) (6.73 +/- 1.46 ng/ml),
      acid phosphatases, total (12.67 +/- 1.15 U/l), and prostatic (2.27 +/- 0.34 U/l),
      were mildly elevated, but declined to normal values at 4 weeks: (2.13 +/- 0.59
      ng/ml; P < 0.01), (7.68 +/- 0.89 U/l; P < 0.01), and (1.39 +/- 0.18 U/l; P <
      0.01), respectively. Mean prostatic volume assessed by ultrasonography showed a
      significant decrease in all patients from 67.84 +/- 8.86 to 37.92 +/- 8.52 cm3; P
      < 0.01, which represents a reduction of 44%. In patients with prostate cancer,
      after the first week of therapy with SB-75, we observed a significant decrease in
      bone pain, relief in urinary outflow obstruction, and reversal of the signs of
      prostatism. Subjective improvement continued during the following weeks of
      treatment, so that the patients no longer needed analgesics. PSA, acid, and
      alkaline phosphatases gradually fell, achieving nearly normal values at 6 weeks.
      Initial serum testosterone levels in BPH and prostatic cancer patients were
      within normal limits, but during treatment with the antagonistic analog SB-75,
      fell to castration values. A major fall in free testosterone levels was observed
      after the first dose; the maximal inhibition was seen after 6-12 hr, with a
      simultaneous decrease in levels of both gonadotropins. Our results show that
      antagonist SB-75 can be safely administered for prolonged periods of time. The
      rapid shrinkage of the prostate and concomitant improvement in obstructive
      symptoms of prostatism obtained with antagonistic analog SB-75 in patients with
      BPH may decrease the morbidity of prostatic surgery and offer a therapeutic
      alternative in men who are considered poor surgical risks.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7508624
TI  - Serum PAPP-A measurements in first-trimester screening for Down syndrome.
AB  - Serum PAPP-A measurements taken from 254 women in the first trimester are
      reported. Eleven chromosomal abnormalities were detected. The mean serum PAPP-A
      levels in cases of Down syndrome were 0.44 MOM at 9 weeks gestation, 0.15 MOM at
      10 weeks, and 0.29 MOM at 11 weeks. The PAPP-A level at 10 weeks was below those
      of pregnancies which aborted spontaneously. At 11 weeks, the pregnancies with
      Down syndrome recorded the lowest PAPP-A levels at that gestation. On this small
      sample, offering chorionic villus sampling to women with singleton pregnancies
      and a PAPP-A level below 0.3 MOM (approximately 6.5 per cent of this at-risk
      group) would have detected all the Down syndrome fetuses at 10 weeks and 50 per
      cent at 11 weeks without selecting those cases destined to abort. This suggests
      that serum PAPP-A should continue to be investigated as a potential first
      trimester screening test for Down syndrome.

PMID- 7508625
TI  - Transabdominal chorionic villus sampling in the second and third trimesters of
      pregnancy: chromosome quality, reporting time, and feto-maternal bleeding.
AB  - Transabdominal chorionic villus sampling (TA-CVS) was performed in 210
      pregnancies from 13 to 38 weeks using a double-needle technique. The sampling
      success was comparable to first-trimester TA-CVS and the diagnostic success rate
      was 98.2 per cent for the short-term technique and 99.3 per cent for cultured
      villi. Two fetuses could not be karyotyped. We found the chromosome quality to be
      similar to that in the first trimester, comparing the number of G-bands and other
      chromosome attributes. There were no unintended losses in a group (n = 142) with
      no sonographic abnormality, except for one death in utero at 38 weeks, 20 weeks
      after sampling. Chromosomal aberrations were seen in 19 per cent of cases with
      abnormal sonograms (n = 58). One cases of a discordant karyotype was found (false
      negative prediction of Down's syndrome by the short-term preparation). There were
      no cases of fetal demise due to feto-maternal bleeding. It is suggested that
      double-needle TA-CVS in advanced pregnancies combines the advantages of rapid
      karyotyping of chromosomes of good quality and low risk for the fetus, and seems
      to be easier to practise and is probably safer than cordocentesis.

PMID- 7508626
TI  - [Multiple endocrine neoplasia type 1. Digestive hormones in the screening].
AB  - Detection of subjects from a multiple endocrine neoplasia type 1 family must rest
      on clinical, biochemical and radiological data, since study of the genome is
      unable to detect these subjects. In the new family described here, 6 out of the
      14 subjects explored were affected. One had a confirmed pancreatic endocrine
      tumour and in 3 others a pancreatic endocrine tumour was highly probable, since
      insulin and glucagon levels, as well as ultrasonic exploration of the pancreas
      were pathological. Measurements of gastrointestinal hormones gave normal results
      in all cases. We conclude that to detect this endocrine neoplasia in subjects at
      risk it seems necessary to measure plasma insulin levels and perform an abdominal
      ultrasonography.

PMID- 7508627
TI  - Structural analysis of the CD2 T lymphocyte antigen by site-directed mutagenesis
      to introduce a disulphide bond into domain 1.
AB  - Many proteins have been predicted to contain domains with immunoglobulin-like
      folds and hence to be members of the immunoglobulin superfamily (IgSF). However,
      several members lack the Cys residues capable of forming the disulphide bond that
      forms a characteristic bridge between the beta sheets in the Ig fold, e.g. domain
      1 of the lymphocyte antigen CD2. The assignment of beta strands in CD2 by
      sequence analysis was tested by attempting to introduce a disulphide bridge
      between the beta sheets by mutating two residues in the relevant positions to
      Cys. Mutant, soluble forms of CD2 were expressed in Chinese hamster ovary cell
      lines and amino acid sequencing showed that a disulphide bond was formed as
      predicted, but not in the control where one Cys residue was misplaced by four
      residues. Evidence that both mutated molecules folded correctly is given by the
      indistinguishable binding of three monoclonal antibodies recognising different
      epitopes on CD2. The 3-D structure of rat CD2 domain 1 has been determined by NMR
      spectroscopy and X-ray crystallography, confirming the predictions from the
      sequence. Applications of this method of insertion of disulphide residues for
      probing protein structures are discussed, together with other structures of IgSF
      domains lacking the typical inter-sheet disulphide bond.

PMID- 7508628
TI  - Artificial protein vaccines with predetermined tertiary structure: application to
      anti-HIV-1 vaccine design.
AB  - A successful approach to the development of a safe and effective synthetic
      vaccine requires that different B and T cell epitopes of the infectious agent be
      included in the vaccine construction. In this paper we suggest a new approach to
      vaccine design in the form of an artificial protein with a predetermined tertiary
      structure (PTS vaccines). Based on B and T cell epitope properties, we
      substantiate the possible use for vaccine construction of one well-known protein
      spatial motif--the four-alpha-helix bundle. Antigenic determinants of cellular
      immunity (amphipathic alpha-helices) and humoral immunity (flexible hydrophilic
      loop regions) are used as blocks for vaccine design. General principles of PTS
      vaccine construction have been applied to anti-HIV-1 vaccine design.

PMID- 7508629
TI  - 5-HT2 receptor antagonists do not reduce ethanol preference in Sardinian alcohol
      preferring (sP) rats.
AB  - The present study investigated the effect of the 5-HT2/1C receptor antagonist
      ritanserin, and of the 5-HT2/D2 receptor antagonist risperidone on ethanol
      preference in Sardinian alcohol-preferring (sP) rats. Rats were offered free
      access to both tap water and 8% (in one experiment 3%) ethanol solution.
      Subchronic (10 or 1 mg/kg/day, for 10 days) or chronic (1 mg/kg/day, for 30 days)
      subcutaneous (SC) ritanserin treatment failed to reduce 8% ethanol preference.
      Risperidone doses that produce marked 5-HT2, but low dopamine D2, receptor
      blockade (1 and 0.1 mg/kg/day, SC, for 9 and 10 days, respectively) did not
      modify 8% ethanol preference. On the other hand, a high risperidone dose (10
      mg/kg/day, SC, for 14 days), which produces pronounced dopamine D2 receptor
      blockade, reduced 8% ethanol preference, like the dopamine receptor antagonist
      haloperidol. Previous studies have shown that both ritanserin and risperidone
      evoke long-lasting and pronounced suppression of 3% ethanol preference in
      genetically nonselected rats. However, in the present study, SC ritanserin
      treatment (1 mg/kg/day for 10 days) did not modify 3% ethanol preference in sP
      rats. The failure of 5-HT2 antagonists to reduce ethanol preference in sP rats
      raises the question whether genetic selection might have resulted in altered
      regulation of 5-HTergic mechanisms in sP rats.

PMID- 7508630
TI  - The major nucleoside triphosphatase in pea (Pisum sativum L.) nuclei and in rat
      liver nuclei share common epitopes also present in nuclear lamins.
AB  - The major nucleoside triphosphatase (NTPase) activities in mammalian and pea
      (Pisum sativum L.) nuclei are associated with enzymes that are very similar both
      biochemically and immunochemically. The major NTPase from rat liver nuclei
      appears to be a 46-kD enzyme that represents the N-terminal portion of lamins A
      and C, two lamina proteins that apparently arise from the same gene by alternate
      splicing. Monoclonal antibody (MAb) G2, raised to human lamin C, both
      immunoprecipitates the major (47 kD) NTPase in pea nuclei and recognizes it in
      western blot analyses. A polyclonal antibody preparation raised to the 47-kD pea
      NTPase (pc480) reacts with the same lamin bands that are recognized by MAb G2 in
      mammalian nuclei. The pc480 antibodies also bind to the same lamin-like bands in
      pea nuclear envelope-matrix preparations that are recognized by G2 and three
      other MAbs known to bind to mammalian lamins. In immunofluorescence assays, pc480
      and anti-lamin antibodies stain both cytoplasmic and nuclear antigens in plant
      cells, with slightly enhanced staining along the periphery of the nuclei. These
      results indicate that the pea and rat liver NTPases are structurally similar and
      that, in pea nuclei as in rat liver nuclei, the major NTPase is probably derived
      from a lamin precursor by proteolysis.

PMID- 7508631
TI  - [Prostate-specific antigen: the most useful marker for prostate cancer].
AB  - Fifteen years after its discovery, Prostate Specific Antigen (PSA) remains the
      most useful marker for prostate cancer. We summarise the biomolecular
      characteristics of PSA and the available assays for its measurement. We define
      its role in the diagnosis of prostate cancer, and discuss its value in the
      monitoring of patients under therapy.

PMID- 7508632
TI  - [C. G. Jung's concept of schizophrenia].

PMID- 7508633
TI  - [Alternative treatment of psychiatric diseases].
AB  - This article gives an overview of the use of unconventional medicine in patients
      with psychiatric and psychosomatic problems. Frequently used methods are herbal
      remedies, homeopathy, acupuncture, various forms of massage and relaxation as
      well as a wide variety of unconventional psychotherapeutic approaches.
      Conceptually, these practices can be grouped into four categories: biological
      pharmacological remedies, physical-energetic methods, esoteric-spiritual
      techniques and psychological treatments. Often patients use these methods on
      their own without contacting a provider, but also without telling their
      psychiatrist. A review of outcome studies shows that effectiveness is difficult
      to assess, as there is substantial controversy on the basic definition of terms
      and mechanisms. The use of complementary methods in psychiatric patients poses
      various questions including compliance and ethical considerations, demanding a
      high flexibility and integrative thinking in psychotherapy.

PMID- 7508634
TI  - [Neurologic expert assessment after whiplash injuries of the cervical spine].

PMID- 7508635
TI  - [New experiences with phototherapy: seasonal depression (SAD) and further
      indications].

PMID- 7508636
TI  - [Revalidation of the Saul and Sheppard "Dream Hostility Counts" in a time series
      of 24 dreams, of which 7 ended in a migraine at awakening].
AB  - Our Series of 24 dreams can be used for validating hostility scales. Nocturnal
      migraine represents an ideal archimedian point (C. G. Jung) from which psychology
      can reach certainties comparable to those of physics. By Pearsons Phi coefficient
      psychological findings can be solidly moored to the "non-psychical", the somatic
      sphere. Revalidation of the Dream-Hostility-Count lead us to a higher degree of
      significance (p < 0.005 instead of p < 0.01) than that reached by Saul and
      Sheppard who used hypertensives for a critical group.

PMID- 7508637
TI  - Depressive inpatients and suicidal behavior: a comparison of suicidal and non
      suicidal depressives.

PMID- 7508638
TI  - Role of NO production in NMDA receptor-mediated neurotransmitter release in
      cerebral cortex.
AB  - L-Glutamate and norepinephrine are examples of a major excitatory
      neurotransmitter and a neuromodulator in the cerebral cortex, respectively.
      Little is known of how chemical signaling between the anatomically distinct
      chemical pathways occurs. Specific activation of the N-methyl-D-aspartate (NMDA)
      class of glutamate receptor in synaptosomal preparations from guinea pig cerebral
      cortex caused release of both of these chemicals, and this release was blocked by
      agents that inhibit nitric oxide (NO) production or remove NO from the
      extracellular space. Furthermore, neurotransmitter release correlated with
      cortical NO production after NMDA receptor stimulation. These results suggest
      that NO production and its extracellular movement may be links in the pathway
      from NMDA receptor activation to changes in chemical signaling in surrounding
      synaptic terminals in the cerebral cortex.

PMID- 7508639
TI  - Effects of pentafraction administration on microvascular permeability alterations
      induced by graded thermal injury.
AB  - BACKGROUND: Pentafraction is a pentastarch derivative hypothesized to limit burn
      edema by "sealing" damaged capillaries, restoring a barrier to fluid
      translocation and macromolecular (protein) flux. METHODS: Canine hind paw lymph
      flow (QL) and lymph (CL) and plasma (CP) protein concentrations were measured
      before and for 6 hours after (1) 5-second 100 degrees C (n = 6) or 80 degrees C
      (n = 6) foot paw scald, (2) 100 degrees C (n = 5) or 80 degrees C (n = 5) foot
      paw scald followed 30 minutes later by a 4 cc/kg bolus of 6% pentafraction, or
      (3) pentafraction infusion without scald (n = 5). Before scald or pentafraction
      infusion, hind paw venous pressure was elevated and maintained by outflow
      restriction until a steady state, minimal CL/CP was reached. The reflection
      coefficient, sigma d, was determined as 1-CL/CP, and the (fluid) filtration
      coefficient (Kf) was calculated. RESULTS: Scalding uniformly produced statistical
      (p < 0.05, ANOVA) increases in QL, CL/CP, sigma d, Kf, and paw weight gain.
      Postburn pentafraction infusion produced no enduring alterations in any measured
      parameter as compared with those of animals who received a matched severity scald
      without pentafraction. CONCLUSIONS: Pentafraction does not appreciably ameliorate
      the adverse microcirculatory consequences observed at the site of burn injury.

PMID- 7508640
TI  - Increased wound-breaking strength induced by insulin-like growth factor I in
      combination with insulin-like growth factor binding protein-1.
AB  - BACKGROUND: Polypeptide growth factors have been shown to accelerate wound repair
      in rodent animal model systems. METHODS: In this report, insulin-like growth
      factor I (IGF-I) and the combination of IGF-I plus insulin-like growth factor
      binding protein (IGFBP-1) were applied directly to linear incisions made through
      dorsal rat skin, and histologic analysis of breaking strength and hydroxyproline
      quantification were performed. RESULTS: IGF-I alone, in contrast to transforming
      growth factor-beta and platelet-derived growth factor, had no effect on wound
      breaking strength. However, the combination of IGF-I plus IGFBP-1 significantly
      increased wound-breaking strength. Wound-breaking strength was increased 33%
      compared with wounds treated with IGF-I alone. IGFBP-1 alone had no effect. The
      ability to stimulate breaking strength was dependent on posttranslation
      modification of IGFBP-1. Phosphorylated IGFBP-1 was without effect, whereas the
      dephosphorylated protein was fully biologically active. This increase in wound
      breaking strength induced by the combination of IGF-I and dephosphorylated IGFBP
      1 was accompanied by an 67% increase in wound hydroxyproline content, whereas the
      combination of IGF-I and the phosphorylated form of IGFBP-1 had no effect.
      CONCLUSIONS: We concluded that IGF-I is a potent stimulant of incisional wound
      healing, but if administered without other growth factors, its effects can only
      be shown when it is combined with one of its specific binding proteins.

PMID- 7508641
TI  - The serotoninergic bulbospinal system and brainstem-spinal cord content of
      serotonin-, TRH-, and substance P-like immunoreactivity in the aged rat with
      special reference to the spinal cord motor nucleus.
AB  - The 5-hydroxytryptamine (5HT) containing bulbospinal pathway was studied with
      immunohistochemical (IF) and chemical techniques in 2-3 and 30 months old male
      Sprague-Dawley rats. The coexisting neuropeptides substance P (SP), thyrotropin
      releasing hormone (TRH) and galanin were also analysed. Furthermore, the
      expression of mRNA encoding aromatic L-amino acid decarboxylase (AADC), prepro
      TRH, and preprotachykinin (prepro-SP) was analysed with in situ hybridization
      (ISH) in the midline raphe nuclei inthe lower brainstem. The results showed a
      decreased number of axonal 5HT fibers with a normal morphology in the ventral
      horn of the aged rat lumbosacral spinal cord, and several 5HT immunoreactive (IR)
      fibers with an aberrant morphology, suggestive of axonal degeneration, were
      intermingled. This was evident in both the dorsal and ventral horn of the spinal
      cord. The 5HT-IR fibers with an aberrant morphology usually also contained TRH
      and/or SP- and/or galanin-like immunoreactivity (LI) in the ventral horn. These
      signs of degeneration were clearly less evident in the thoracic and cervical
      spinal cord segments. Moreover, these changes varied between aged litter-mates.
      This was in agreement with behavioural signs of motor disturbances, present in
      about 40% of the aged rats and which in all cases were confined to the hindlimbs.
      Chemical analyses disclosed significantly lower levels of TRH-LI and, in
      particular, SP-LI in both the ventral and dorsal quandrants of the spinal cord in
      the aged rat compared to young adults. The differences were largest in the lumbar
      regions of the spinal cord. Corresponding analysis of 5HT and 5
      hydroxyindoleacetic acid (5HIAA) in the same tissue specimens revealed largely
      unaltered levels of 5HT and a slight increase in 5HIAA, indicating the
      possibility of an increased 5HT turnover in the aged rat spinal cord. Neurons in
      nucleus raphe obscurus and nucleus raphe pallidus were immunoreactive to 5HT, and
      after pretreatment with colchicine to TRH-, SP-, and galanin-LI as well. There
      was no obvious difference in number of labeled cells, or labeling intensity,
      between colchicine-treated young adult and aged rats, although, in the
      corresponding region of medulla oblongata, chemical analysis disclosed
      significantly lower levels of 5HT, TRH, and, in particular, SP in untreated aged
      rats. In contrast, in situ hybridization analysis revealed increased mRNA levels
      encoding prepro-TRH and prepro-SP in old rats, while mRNA content encoding AADC
      mRNA was similar in young adult and aged rats.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7508642
TI  - The effect on the safety of intravenous immunoglobulin of testing plasma for
      antibody to hepatitis C.
AB  - BACKGROUND: The safety of intravenous immunoglobulin (IGIV), manufactured from
      units testing negative for antibody to hepatitis C virus (anti-HCV), was
      investigated. STUDY DESIGN AND METHODS: A study involving five chimpanzees was
      performed to determine whether the safety of IGIV would be compromised if units
      of plasma that reacted for anti-HCV were withheld from pools from which IGIV is
      manufactured. In the first phase of the experiment, two chimpanzees were infused
      with 25 mL per kg of unprocessed, pooled plasma from 2887 donors who did not
      react for anti-HCV in single-antigen (c100-3) enzyme-linked immunosorbent assays.
      In the second phase, each of three chimpanzees was infused with 1000 mg per kg of
      IGIV manufactured from the same plasma units. The immunoglobulin was made by
      seven United States-licensed manufacturers, each using its own approved method.
      Each chimpanzee received an equal dose of each manufacturer's IGIV. RESULTS: The
      two chimpanzees that received anti-c100-3-nonreactive, unprocessed pooled plasma
      became infected with HCV. The three chimpanzees infused with IGIV did not show
      any evidence of infection with HCV 15 months after inoculation. Two of these
      animals were challenged with human non-A,non-B hepatitis-infectious plasma, and
      both subsequently showed evidence of HCV infection. CONCLUSION: These studies
      demonstrate that, as determined by infectivity for chimpanzees, 1) the
      withholding of plasma units that react for anti-c100-3 from pools from which
      plasma products are manufactured does not render the source material
      noninfectious, and 2) the safety of IGIV manufactured from such plasma pools is
      not compromised by withholding the units that react for anti-c100-3.

PMID- 7508643
TI  - Hepatitis C viral markers in patients who received blood that was positive for
      hepatitis C virus core antibody, with genetic evidence of hepatitis C virus
      transmission.
AB  - BACKGROUND: Despite the use of the anti-c100-3 assay for blood donor screening,
      posttransfusion non-A,non-B hepatitis still occurred. A more sensitive assay
      should be developed to prevent this. STUDY DESIGN AND METHODS: Stored serum
      specimens from 2020 healthy blood donors who were negative for c100-3 antibody to
      hepatitis C virus (HCV) were retrospectively screened for the presence of
      antibodies against a core protein of HCV using an enzyme-linked immunosorbent
      assay and Western blot analysis as part of a study on posttransfusion non-A,non-B
      hepatitis. RESULTS: Eight (0.4%) of the 2020 donors were positive for HCV core
      antibody. Posttransfusion non-A,non-B hepatitis occurred in 5 of five patients
      known to have received blood that was positive for HCV core antibody and 1 of 141
      patients transfused with blood that was negative for HCV core antibody. The total
      incidence of posttransfusion non-A,non-B hepatitis was 4.1 percent (6/146). The
      nucleotide sequence of the nonstructural 5 region of the HCV genome obtained from
      two donors and corresponding recipients was also analyzed. The HCV genome
      sequences were identical for one donor-recipient pair, and there was 99.4-percent
      homology for a second pair. CONCLUSION: Anti-core-positive blood proved to be
      highly infectious for HCV, and this validated the use of the second-generation
      anti-HCV assay for blood donor screening.

PMID- 7508644
TI  - Altered expression of adhesion molecules (L-selectin and Mac-1) on granulocytes
      during storage.
AB  - BACKGROUND: The success of granulocyte transfusion therapy for neutropenic
      patients with sepsis is dependent on the number and quality of the granulocytes
      transfused. There is a progressive impairment in granulocyte function during
      storage. STUDY DESIGN AND METHODS: The effect of 1 to 2, 4, 24, and 48 hours'
      storage on receptor expression associated with granulocyte function has been
      analyzed. RESULTS: After 24 hours' storage, significant changes were found in the
      expression of receptors associated with adhesion to the endothelium: a decrease
      in L-selectin expression (p < 0.01) and an increase in Mac-1 expression (p <
      0.01). Receptors (CR1 and FcRIII), associated with adhesion to target, were
      either increased (CR1) or unaltered (FcRIII). The capacity to produce a reactive
      oxygen metabolite (hydrogen peroxide) remained essentially unchanged after 48
      hours' storage. The ability of N-formyl-methionyl-leucyl-phenyl alanine to
      mobilize Mac-1 and CR1 was reduced after 48 hours' storage. CONCLUSION: Since the
      regulation of adhesion molecules is important for the recruitment of granulocytes
      into an inflammatory site, the observed in vitro changes in L-selectin and Mac-1
      expression during storage may be of importance for the quality of granulocyte
      concentrates.

PMID- 7508645
TI  - The effect of a thromboxane A2 receptor antagonist (ONO 3708) on ischemia
      reperfusion injury of the dog pancreas.
AB  - The effects of a thromboxane A2 receptor antagonist, ONO 3708, on ischemia
      reperfusion injury of the pancreas were evaluated using an isolated in-vivo
      perfused dog pancreas model. Pancreatic endocrine and exocrine function were
      stimulated with cholecystokinin octapeptide (10(-12) mol). This dose
      significantly increased endogenous prostaglandin I2 and thromboxane A2 production
      by the pancreas (both P < 0.001). A period of 60 min of ischemia and subsequent
      reperfusion induced an increase of pancreatic amylase release (P < 0.01) and a
      decrease of insulin release (P < 0.01). There was also a decrease of pancreatic
      juice and pancreatic bicarbonate and amylase output (au P < 0.01), suggesting
      damage to the acinar, ductular, and beta cells. Intravenous administration of ONO
      3708 (200 micrograms/kg/min) throughout the experiment prevented these
      abnormalities of pancreatic secretion. It also reduced the plasma lipid peroxide
      level in the venous drainage (P < 0.01) and elevated the prostaglandin I2 level
      (P < 0.01) without changing thromboxane A2 levels. ONO 3708 thus appeared to
      protect the pancreas from ischemia-reperfusion injury by reducing the
      peroxidation of cell membrane lipids and by decreasing the thromboxane
      A2/prostaglandin I2 ratio, which is a predictor of cellular injury.

PMID- 7508646
TI  - An organotypic skin culture model in dogs. A model for transplantation
      immunopathology in canine systems.

PMID- 7508647
TI  - Immunohistologic staining of cytotoxic T and NK cells in formalin-fixed paraffin
      embedded tissue using microwave TIA-1 antigen retrieval.

PMID- 7508648
TI  - Quantitation of RNA using the polymerase chain reaction.
AB  - Sequential use of reverse transcriptase and the polymerase chain reaction (RT
      PCR) permits rapid and sensitive detection of specific RNAs. However, the
      greatest advantage of RT-PCR, its remarkable sensitivity, has also limited its
      usefulness in quantitative applications, since the effects of minor variations in
      reaction conditions from sample to sample are greatly magnified during the
      amplification process. Several recently developed techniques circumvent this
      problem, allowing accurate quantitation of RNA using RT-PCR.

PMID- 7508649
TI  - [The effect of different types of recombinant interferon on the induction of 2,5
      oligoadenylate synthetase in natural killers and the tumor cells in bladder
      cancer patients].
AB  - Recombinant interferon treatment of donors' and bladder cancer patients'
      lymphocytes results in activation of natural killer cells which is in correlation
      with enhanced activity of 2,5-oligoadenylate synthetase in them. The study of
      sensitivity of bladder cancer cell primary cultures showed that the cells are
      sensitive to various interferons virtually in all the cases observed as indicated
      by high synthetase activity. The baseline level of 2,5-oligoadenylate synthetase
      in tumor cells surpassed that in natural killers from healthy donors which may be
      related to elevated levels of serum gamma-interferon in the above patients.

PMID- 7508650
TI  - [The characteristics of the surgical procedure in patients with the complications
      of prostatic adenoma and severe concomitant diseases].
AB  - Basing on the results obtained in 380 patients, the efficacy of radical surgery
      of prostatic adenoma was studied in 3 groups of patients: group 1 (136 patients)
      underwent urgent adenomectomy because of acute urine retention; group 2 (153
      patients) with severe concomitant diseases underwent one or two-stage
      adenomectomy; group 3 (92 patients) without clinically manifested somatic
      pathology. The author shows practical significance of urgent (within 72 hours)
      and delayed (within 5-10 days) radical adenomectomies in surgery of patients with
      acute urine retention. Long-term preoperative therapy of circulatory disorders
      and diabetes mellitus allowed performance of radical adenomectomy in additional
      20-30% of group 2 patients. Positive outcomes were achieved in 88.2%, 80.4%,
      93.4% of patients from groups 1, 2 and 3, respectively. Urination recovered in
      98.5% of those operated on. Hospital lethality was 9.7%. Its cause was mainly
      purulent pyelonephritis (70.3%), the rest lethal outcomes occurred due to
      circulatory, respiratory and gastrointestinal diseases.

PMID- 7508651
TI  - [Corneal neovascularization: the current aspects of its pathogenesis and
      treatment].

PMID- 7508652
TI  - Production of a monoclonal antibody to the light chain of the bovine beta 2
      integrin family (BoCD18).

PMID- 7508653
TI  - Comparison of workshop CD45R monoclonal antibodies with OvCD45R monoclonal
      antibodies in sheep.
AB  - The reactivity of the antibovine monoclonal antibodies (mAbs) comprising
      temporary cluster TC1 was compared with that of two OvCD45R mAbs on sheep cells.
      Three of the mAbs--CC31, CC99 and CC103--did not cross-react with sheep cells.
      All the workshop mAbs precipitated two molecules of apparent molecular weight
      (MW) 200 kDa and 220 kDa while the antisheep CD45R mAb 20-96 precipitated a
      single band of 220 kDa. Cell surface expression was examined by single colour
      FACS (fluorescence activated cell sorting) analysis of efferent and afferent
      lymph cells and peripheral blood lymphocytes and the distribution of the antigens
      on CD4+, CD8+ and T19+ (WC1) and B cells was determined by two colour
      fluorescence staining. By cellular distribution and immunohistology the TC1 mAbs
      could be divided into four distinct groups which differed from a fifth group
      comprising the two OvCD45R antibodies.

PMID- 7508654
TI  - Clustering of monoclonal antibodies recognizing different members of the WC1 gene
      family.
AB  - Mouse L cell lines expressing two different bovine WC1 glycoproteins were
      produced by transfection of the cells with the corresponding cDNAs. The cell
      lines were used to analyze the reactivities of 67 monoclonal antibodies (mAbs)
      which recognize bovine gamma/delta T cells. The results indicated that
      preliminary clustering of mAbs can be achieved based on their recognition of
      epitopes expressed on all gene products, or of epitopes encoded by individual
      members of the gene family. The studies also showed that at least three members
      of the WC1 gene family are expressed, although it is not yet known how many can
      be expressed by individual bovine gamma/delta T cells. Final clustering of the
      WC1 mAbs will not be possible until the exact number of expressed gene products
      is known, and the reactivities of the mAbs with these products have been
      analyzed.

PMID- 7508655
TI  - Identification of monoclonal antibodies specific for the gamma/delta TCR.
AB  - Twelve monoclonal antibodies (mAbs) formed temporary cluster TC36. mAb CACTB6A
      was included as a standard antibody that reacted with the gamma/delta T cell
      receptor (TCR). Eight of the mAbs, CACTB6A, CACT16A, CACT17A, CACTB12A, CACTB44A,
      CACT71A, CACT18A and CACT61A, immunoprecipitated a 47 kDa molecule indicating
      that they all recognize the gamma/delta TCR. Flow cytometric studies separated
      these mAbs into three groups that distinguish three different gamma/delta TCR.
      mAb BAQ72A, which fell within TC36, immunoprecipitated a 215 kDa molecule with a
      similar tissue and cellular distribution to BoWC1 mAb. mAbs CACT26A, CACT63A and
      CACT77A reacted similarly to each other by flow cytometry and immunohistology,
      but were distinct from the other mAbs in TC36. These three mAbs may recognize an
      activation molecule and form a distinct novel mAb cluster.

PMID- 7508656
TI  - Characterization of a late activation antigen defined by monoclonal antibodies of
      cluster BoWC8 (TC23).
AB  - Three monoclonal antibodies (mAbs), P13 (#90), IL-A78 (#76) and IL-A79 (#77),
      defined a new cluster, called BoWC8. The antigen defined by these mAbs is a
      molecule of 160 kDa under reducing conditions, and is expressed on lymphocytes
      late (6 days) after activation. The molecule can be expressed on multiplying T
      cells, but not on B cells.

PMID- 7508657
TI  - A new non-lineage specific antigen with an M(r) of 115 kDa and 39 kDa present on
      bovine leukocytes identified by monoclonal antibodies within BoWC10.
AB  - Five mAbs out of a total of 189 submitted to the Second Workshop were shown to be
      similar when statistical analyses of flow cytometry data were performed. For the
      duration of the workshop the five mAbs were assigned to temporary cluster TC35.
      The mAbs precipitated two polypeptides by SDS-PAGE under reducing conditions. One
      had an M(r) of 115 kDa, the other an M(r) of 39 kDa. The antigen recognized was
      present on thymocytes, a subpopulation of CD2+ T cells and a major subpopulation
      of B cells. The antigen is upregulated after long-term activation with
      concanavalin A. It is proposed that the mAbs in TC35 should be regarded as a
      single cluster identifying a novel leukocyte differentiation antigen in cattle.
      These mAbs were accepted as a new workshop cluster BoWC10.

PMID- 7508658
TI  - Biochemical characterization of three non-lineage antigens defined by workshop
      antibodies.
AB  - Monoclonal antibodies (MAbs) from three temporary clusters recognized antigens
      expressed on platelets and a wide variety of other tissues. To confirm the
      clustering of the mAbs, we biochemically characterized the antigens recognized by
      each cluster. TC9 (BoCD44) contained mAbs to a 95 kDa ruminant antigen,
      homologous to human CD44. TC11 (BoWC9) defined a 25 kDa antigen and TC7 (BoWC11)
      defined an antigen composed of two subunits of 49 and 79 kDa.

PMID- 7508660
TI  - Use of the MAIEA technique to confirm the relationship between the Cromer
      antigens and decay-accelerating factor and to assign provisionally antigens to
      the short-consensus repeats.
AB  - The MAIEA (monoclonal-antibody-specific immobilisation of erythrocyte antigens)
      assay has recently been developed for the assignment of red cell antigens,
      recognised by human alloantisera, to particular membrane components of the red
      cell membrane. This technique detects trimolecular complexes formed by the
      reaction of a human antibody and a mouse antibody with a particular red cell
      protein. A positive reaction, in an ELISA-type detection procedure, occurs if the
      epitopes to the human and mouse antibodies are present on the same membrane
      component but at different regions. In this report, we show how the MAIEA assay
      can be used to confirm the relationship between Cromer system antigens and the
      complement-regulatory protein, decay-accelerating factor (DAF, CD 55). In
      addition, the location of the antigens along the protein is postulated by using
      three anti-DAF monoclonal antibodies with specificities to different regions of
      DAF. Tca and Esa are assigned provisionally to the first short-consensus repeat
      (SCR), UMC to the second SCR, Dra to the third SCR and Cra, WESa and WESb to the
      fourth SCR or to the serine/threonine rich region of the DAF protein.

PMID- 7508659
TI  - Effect of prestorage leukocyte reduction on proteins of platelets obtained by
      apheresis.
AB  - The effect of prestorage leukocyte reduction was evaluated on platelet
      concentrates (PCs) obtained by apheresis using the 'surge' technique. Two hours
      after collection, the PCs were divided into 2 equal units. One unit was filtered
      through a Sepacell PL-10a, producing a filtered PC (FPC). The second unit
      constituted a non-filtered PC (NFPC). FPCs and NFPCs were stored at room
      temperature in 1,400-ml CLX bags on a horizontal agitator up to 7 days. We
      analyzed platelet samples obtained during storage from NFPCs and FPCs at days 1,
      3 and 7. The expression of membrane glycoproteins (GP)Ib and GPIIb/IIIa (assessed
      by flow cytometry), platelet response to thrombin and ristocetin (aggregometry)
      and global platelet protein pattern (studied by high-resolution two-dimensional
      gel electrophoresis) remained stable over the 7 days of storage in NFPCs as well
      as in FPCs. However, in both preparations, the expression of GMP-140 (flow
      cytometry) progressively increased during storage. Our in vitro study indicates
      that early leukocyte reduction by filtration of apheresis PCs does not induce
      modifications in platelet GPs and protein patterns.

PMID- 7508661
TI  - Is dialysis environment more important than blood transfusion in transmission of
      hepatitis C virus during hemodialysis?

PMID- 7508662
TI  - [Effector cells in allergy: biological principles and new pharmacologic
      concepts].
AB  - The clinical symptoms of allergy are caused by cellular (IgE-triggered) responses
      to an allergen. Effector cells of allergy include eosinophil and basophil
      granulocytes, as well as tissue mast cells. Growth and accumulation, as well as
      IgE-dependent and independent functions of these cells are regulated by distinct
      proteohormones and peptides. The hemopoietic cytokines IL-3 (interleukin-3), IL-5
      and GM-CSF (granulocyte-macrophage colony-stimulating factor) are involved in the
      regulation of basophils (and eosinophils), whereas the ligand for c-kit, SCF
      (stem cell factor) is a mast cell-specific agonist. Basophils and mast cells
      express high-affinity IgE-binding sites. Allergen binding to IgE on mast cells
      and basophils, and consecutive cross-linking of IgE receptors is followed by
      production and/or secretion of inflammatory mediator substances. Specific
      activation and deactivation of mast cells/basophils in vitro has been
      demonstrated by use of recombinant cytokines and allergens, and specific haptens
      or by use of novel drugs, and should lead to epitope-specific diagnosis and
      better management of allergic diseases in the future.

PMID- 7508663
TI  - [New concepts in therapy of type I allergic diseases].
AB  - The molecular characterization of allergens with recombinant DNA techniques
      allowed cDNA sequences to be obtained and, hence, information regarding the
      primary structure of allergens. It is now possible to express well-defined
      recombinant allergens in heterologous expression systems and to obtain large
      amounts of highly pure recombinant allergens for the improvement of current
      diagnosis and therapy of type I allergic diseases. Due to extensive cross
      reactivities and structural similarities of the relevant allergens it is possible
      to define a limited number of allergens, which is a prerequisite for allergen
      specific therapeutic concepts. Specific concepts of active immunotherapy and
      strategies of passive therapeutic interference based on recombinant techniques
      are discussed.

PMID- 7508664
TI  - Specificity of antibodies reactive with hepatitis B surface antigen following
      immunization with synthetic peptides.
AB  - The amino acid sequence 139-147 from hepatitis B surface antigen (HBsAg) has
      previously been shown to represent a B-cell epitope with potential as a component
      of a synthetic peptide vaccine against hepatitis B. In this paper, two regions of
      HBsAg which act as T-cell epitopes in inbred mice have been identified (residues
      23-34 and residues 160-171). The ability of synthetic peptides representing these
      epitopes to provide help for the production of antibody against the 139-147
      epitope has been assessed following their co-linear synthesis with the B-cell
      epitope and following co-immunization of the peptides in an uncoupled form. Both
      these strategies result in the induction of anti-peptide antibodies which
      specifically react with recombinant HBsAg. The results presented give further
      support to the concept that synthetic peptides representing appropriately chosen
      B- and T-cell epitopes from HBsAg could form the basis of a synthetic vaccine
      against hepatitis B.

PMID- 7508665
TI  - Enhanced pulmonary pathology associated with the use of formalin-inactivated
      respiratory syncytial virus vaccine in cotton rats is not a unique viral
      phenomenon.
AB  - The specificity of viral antigens in the formalin-inactivated, alum-precipitated
      respiratory syncytial virus (FI-RSV) vaccine in augmenting the pulmonary
      inflammatory response was evaluated. Cotton rats were immunized with a FI-RSV
      vaccine derived from Vero cells, a monkey cell line, or HEp-2 cells, a human cell
      line. The FI-RSV/Vero and the FI-RSV/HEp-2 vaccines were prepared similarly to
      the original Lot-100 FI-RSV vaccine that was associated with enhanced disease in
      the mid-1960s field trials. Each vaccine was administered intramuscularly at
      various doses and intervals. At 1, 4 or 7 weeks after the last vaccine dose,
      cotton rats were challenged with 10(6) plaque-forming units of live RSV grown in
      HEp-2 cells. For controls, FI-parainfluenza, FI-HEp-2 and alum vaccines, and live
      RSV primary infection were used. For measuring virus replication and
      histopathology, lungs were harvested at 4 and 8 days postchallenge. A dose
      response relationship to vaccine dose was observed for ELISA, neutralizing and
      antifusion antibodies. All animals given three doses or two of the higher doses
      of FI-RSV/Vero vaccine developed significant neutralizing antibody, were
      protected against pulmonary virus replication and had similar low levels of
      histopathology compared with live RSV and controls. Two immunizations of the
      lowest dose of FI-RSV/Vero vaccine did not induce neutralizing antibody, did not
      provide protection of the lung against RSV and did not enhance the pulmonary
      cellular response. However, FI-RSV/HEp-2 vaccine was associated with significant
      enhanced pulmonary histopathology despite inducing high titres of neutralizing
      antibody and protecting the lungs against RSV infection.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7508666
TI  - A rejected letter to the editors of the Lancet and the need for angiologists to
      prove their usefulness.

PMID- 7508667
TI  - Sensory and sympathetic nerve sprouting in the rat cornea following neonatal
      administration of capsaicin.
AB  - Corneal sensory and sympathetic nerves exert opposing actions on corneal
      mitogenesis and wound healing. The mechanisms by which these nerves exert their
      actions are unknown; however, the release of axonally transported neuropeptides
      has been postulated. In the present study, we investigated changes in innervation
      densities of calcitonin gene-related peptide (CGRP-) and tyrosine hydroxylase (TH
      )immunoreactive (IR) nerves of the rat cornea following neonatal capsaicin
      administration, and the relationships between these changes and the development
      of neuroparalytic keratitis. Newborn rats were injected with capsaicin on each of
      the first 3 days of life. Forty-eight hours after the last injection, corneal
      CGRP immunostaining had totally disappeared from the cornea, whereas TH
      immunostaining was relatively unaffected. Over the next several weeks, a dramatic
      reinnervation of the cornea took place. By 6-8 weeks both the CGRP- and TH-IR
      corneal innervation density in the capsaicin-treated animals exceeded that of age
      matched control or normal animals; that is, the corneas had become "hyper
      reinnervated." The pattern of innervation that returned was grossly abnormal and
      was characterized by the presence of a bizarre subepithelial plexus of fine
      stromal sprouts; an abundance of myelinated axons; and complex, atypical,
      epithelial leash morphologies. Retrograde transport of wheatgerm agglutinin
      conjugated to horseradish peroxidase (WGA:HRP) from the central cornea in control
      and capsaicin-treated adult animals labeled an average of 143 and 47 trigeminal
      ganglion cells, respectively (with mean diameters of 25.7 +/- 0.49 microns and
      34.3 +/- 0.72 microns), suggesting a 67% decrease in corneal afferent neurons in
      the capsaicin-treated animals. Transection of the ophthalmomaxillary nerve in
      adult capsaicin-treated animals completely eliminated corneal CGRP-IR staining,
      and extirpation of the superior cervical ganglion resulted in the loss of 70-80%
      of corneal TH-IR nerves, thus demonstrating the sensory and predominantly
      sympathetic origins, respectively, of these fiber populations. Chronic keratitis
      and neovascularization developed in the capsaicin-treated animals by
      approximately 3 weeks of age, achieved a maximum intensity between 4 and 6 weeks,
      and showed some gradual improvement thereafter. However, the keratitis never
      completely disappeared, even after 13 months. In conclusion, these data show that
      corneal sensory (CGRP-IR) and sympathetic (TH-IR) nerve fibers undergo extensive
      sprouting following partial corneal sensory denervation with the neurotoxin
      capsaicin. However, the resultant "hyper-reinnervation" is morphologically
      abnormal and, for reasons unknown, functionally incapable of preventing or
      totally reversing the keratitis.

PMID- 7508668
TI  - Effects of low doses of aprotinin on clotting times activated with celite and
      kaolin.
AB  - The effects of aprotinin (2 x 10(6) and 4 x 10(6) PIU Iniprol) on the activated
      clotting time (ACT) with both celite- and kaolin-activated tubes were
      investigated in 52 patients, scheduled for elective coronary artery bypass
      grafting. Two whole blood samples (2 ml sample volume) were tested simultaneously
      with Hemochron automated timing systems at different intervals before, during and
      after cardiopulmonary bypass. At none of the times of measurement there was a
      difference in ACT measured with celite or with kaolin as coagulation activator.
      It is concluded that when aprotinin is used in this low dose regimen, celite- and
      kaolin-activated tubes are equally reliable for monitoring ACT.

PMID- 7508669
TI  - Immediate and delayed effects of a brief period of calcium loading, induced by
      the calcium channel agonist Bayer K 8644, on the ultrastructure and sarcolemmal
      integrity of murine diaphragm in vitro.
AB  - Exposure of in vitro mouse diaphragm to the dihydropyridine Ca2+ channel agonist
      Bayer K 8644 (Bay) and partial depolarisation for 120 min induced severe
      structural damage within 30-60 min and membrane permeabilisation (60-120 min).
      Exposure to Bay and depolarisation for 30 min (brief Ca2+ loading) followed by
      washout for 90 min produced similar effects, even though significant membrane
      damage does not occur until the second hour of incubation. Development/expression
      of necrosis during the washout period was not inhibited by manoeuvres designed to
      combat the effects of any remaining Bay, or by use of a Ca(2+)-free, 1 mM EGTA
      medium for washout. Exposure to Bay for 15 min followed by washout did not induce
      damage. Electron microscopic examination revealed that the mitochondria of cells
      fixed after 30 or 120 min exposure to Bay and depolarisation were in the orthodox
      (swollen) configuration, but that mitochondria in muscles that had undergone
      washout with Ca(2+)-free-EGTA saline were electron dense. Further incubation of
      these muscles in Ca(2+)-containing medium caused readoption of the swollen
      configuration. We conclude that membrane permeabilisation can occur after removal
      of the Ca2+ load, and that mitochondrial Ca2+ overload is not necessary for
      Ca(2+)-induced damage/death to occur.

PMID- 7508670
TI  - Adoptive transfer of experimental allergic neuritis in the immune suppressed
      host.
AB  - Experimental allergic neuritis (EAN) was induced in normal and irradiated Lewis
      rats by passively transferring T cells sensitized to SP-26, a peptide fragment of
      P2 myelin protein. The recipients became sick 4-8 days post transfer and the
      degree of disability correlated directly with the dose of T cells. Smaller doses
      caused demyelination of nerve roots and sciatic nerves and larger doses produced
      more severe demyelination and significant axonal degeneration. Irradiated
      recipients developed similar clinical EAN and showed macrophage-mediated
      demyelination despite severe suppression of the host inflammatory response.

PMID- 7508671
TI  - Drainage of molecules from subarachnoid space to spinal nerve roots and
      peripheral nerve of the rat. A study based on Evans blue-albumin and lanthanum as
      tracers.
AB  - The purpose of the present investigation was to find out if a compound injected
      into the spinal subarachnoid space, after having entered ventral and dorsal nerve
      roots, can be traced to the epineurial-perineurial sheaths and the endoneurium of
      peripheral nerves. This would indicate a centrifugal movement of substances from
      the cerebrospinal fluid along nerves; one route of drainage of cerebrospinal
      fluid which in the past has been widely discussed. In vivo studies were made
      using Evans blue-albumin and lanthanum chloride as tracers. Evans blue-albumin is
      macromolecular in size and emits a red fluorescence after exposure to ultraviolet
      light. Lanthanum ions are small and easily visible in the electron microscope.
      The tracers were injected into the cervical subarachnoid space and 15 min to 24 h
      later samples from roots, dorsal root ganglia, proximal part of spinal nerves and
      the median nerves were taken and further processed for detection of tracers.
      Fluorescence microscopy from samples removed 15 min and 24 h after the injection
      of Evans blue-albumin showed a red fluorescence of low intensity in the
      endoneurium of nerve roots, ganglia and proximal spinal nerve. After 24 h also
      the median nerve elicited some fluorescence. The sheaths around these structures
      were also fluorescent. Lanthanum was detected between cell layers of the nerve
      root sheath as well as inside the nerve root parenchyma. In about 50% of the
      samples from dorsal root ganglia extracellular lanthanum was found in the
      capsule. The tracer was also found in the epineurium of 50% of the spinal nerves
      and occasionally in the perineurium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508672
TI  - alpha-Fetoprotein producing gastric carcinomas: a comparative study of three
      different subtypes.
AB  - Nine cases of gastric carcinoma with excessive production of alpha-fetoprotein
      (AFP) were analyzed morphologically, histochemically and biochemically.
      Consequently, it was proposed that AFP-producing gastric carcinomas should be
      divided into three subtypes: (i) hepatoid type; (ii) yolk sac tumor-like type;
      and (iii) fetal gastrointestinal type. The data from the study suggested that the
      hepatoid type and the yolk sac tumor-like type are derived from liver cell
      metaplasia and yolk sac cell metaplasia of common poorly differentiated medullary
      adenocarcinoma, respectively. The fetal gastrointestinal type seemed to be a
      result of the imitation of fetal gastrointestinal epithelium by common tubular
      adenocarcinoma. The hepatoid type was also the most common in the file of AFP
      producing gastric carcinoma. Unfortunately, most of the hepatoid types seemed to
      be highly malignant.

PMID- 7508673
TI  - Immunohistochemistry of molar and non-molar placentas with special reference to
      their differential diagnosis.
AB  - An immunohistochemical study analyzing distributions of beta-subunit human
      chorionic gonadotropin (beta HCG), human placental lactogen (HPL), placental
      alkaline phosphatase (PLAP), and monoclonal anti-cytokeratin (PKK1) was
      undertaken to determine whether the reactivity of these antigens might assist in
      the differential diagnosis of molar and non-molar hydropic placentas. A total of
      16 complete hydatidiform moles, 15 partial hydatidiform moles, 12 hydropic
      abortuses and 39 non-hydropic placentas with gestational age ranging from 4 to 40
      weeks was examined. In both the complete and partial moles, many
      syncytiotrophoblasts stained for beta HCG, HPL, PLAP and PKK1 although the
      staining intensity of beta HCG in the partial moles was weak compared with the
      complete moles. The staining patterns in the hydropic abortuses were almost the
      same as those in the normal first trimester placentas and had no distinct
      features from the partial moles. Trophoblastic hyperplasia is an essential
      feature in differentiating partial moles from hydropic abortuses. With regard to
      the immunostaining patterns of these antibodies, there was no significant
      difference to enable delineation between partial and complete moles, or between a
      hydropic abortus and a partial mole. Monoclonal anti-cytokeratin was most
      sensitive for trophoblasts, but less specific for intermediate trophoblasts than
      HPL. Although an immunohistochemical study using antibodies against beta HCG,
      HPL, PLAP and PKK1 is very useful for characterizing various trophoblasts, it is
      considered that an immunohistochemical study may not be a suitable tool for the
      differential diagnosis of molar and non-molar hydropic placentas.

PMID- 7508674
TI  - Rhythmic contractions of isolated small arteries from rat: role of calcium.
AB  - In order to investigate the mechanisms behind rhythmic contractions in small
      arteries of the mesenteric arcade from Wistar rats, the calcium dependency of the
      oscillations in response to noradrenaline activation was tested on isolated
      vessels. Application of 1 microM ryanodine or 30 microM TMB-8 (procedures known
      to inhibit Ca2+ release from intracellular stores) totally abolished the rhythmic
      activity, even though the antagonists had opposite effects on the amplitude of
      the contractile response to noradrenaline. Verapamil (1 microM) or felodipine (1
      nM) (agents known to inhibit influx of extracellular Ca2+) also abolished the
      oscillations and reduced the maximal noradrenaline response by about 40%.
      Reducing the extracellular Ca2+ concentration to 0.1 mM reduced the amplitude of
      the noradrenaline response to a similar extent as 1 nM felodipine, but did not
      eliminate the oscillations. This may indicate that the effect of calcium entry
      blockers was to eliminate the voltage-dependency of Ca2+ inflow rather than just
      reducing the Ca2+ level. Manoeuvres that would increase the cytosolic Ca2+
      concentration (exposure to caffeine or to the calcium agonist BAY-K 8644)
      increased the frequency of the oscillations. These observations indicate an
      important role, not only for voltage-operating channels, but also for
      intracellular calcium stores in the generation of rhythmic contractions in these
      small arteries. Oscillations appear to be generated by an interplay between
      membrane activation and intracellular calcium stores.

PMID- 7508675
TI  - Risperidone versus perphenazine in the treatment of chronic schizophrenic
      patients with acute exacerbations.
AB  - Risperidone (RIS), a new neuroleptic with 5-HT2- and dopamine D2 receptor
      blocking properties, was compared with perphenazine (PER) in a double-blind,
      multicentre, parallel-group study in 107 chronic schizophrenics with acute
      exacerbation. RIS 5-15 mg or PER 16-48 mg daily was given for 8 weeks.
      Psychopathology was assessed with the Positive and Negative Syndrome Scale
      (PANSS) and Clinical Global Impression. Seventy-eight patients completed the
      trial; there was an equal number of dropouts on both drugs. The mean daily dose
      at endpoint was 8.5 mg RIS and 28 mg PER. The reduction in total PANSS score to
      endpoint did not differ significantly, although there was a tendency in favour of
      RIS. The number of patients with predominantly negative symptoms who showed at
      least 20% reduction in total PANSS score was significantly larger in the RIS
      group. Furthermore, the number of patients showing at least 20% reduction in
      Brief Psychiatric Rating Scale (BPRS) score (BPRS being a subscale of PANSS) was
      significantly larger in the RIS group. The hostility cluster of BPRS improved
      more on RIS than on PER in the endpoint analysis. The overall prevalence of side
      effects was fairly similar in the two groups.

PMID- 7508676
TI  - Relationship of cerebral blood flow disturbances with brain oedema formation.
AB  - Brain oedema is an important factor which compromises maintenance of the cerebral
      blood flow. Conversely, primary blood flow disturbances are leading to brain
      oedema. The mechanisms underlying blood flow impairment by brain oedema are
      associated with an increased regional tissue pressure in proportion to the degree
      of water accumulation in the parenchyma. The release of vasoactive mediator
      compounds might be considered in addition. Primary disturbances of the cerebral
      blood flow, such as focal or global cerebral ischaemia are leading to an
      increased cerebral water content. A decrease of the cerebral blood flow to ca.
      40% of normal or below has been found to result in the development of brain
      oedema. This flow threshold is in the neighbourhood of the ischaemic flow level
      causing irreversible tissue damage. Whereas in focal ischaemia oedema formation
      is a function of the severity of the flow decrease, it is a pathophysiological
      hallmark of early postischaemic recirculation in global cerebral ischaemia.
      Nevertheless, during complete interruption of cerebral blood flow translocation
      of interstitial fluid into the intracellular compartment occurs as manifestation
      of ischaemic cell swelling. Cell swelling under these conditions may, however,
      not necessarily indicate cell damage, but more likely a compensatory response
      attributable to the uptake of excitotoxic transmitters such as glutamate, and of
      K(+)-ions which are excessively released at the onset of ischaemia into the
      extracellular space. Purpose of the swelling process, thus, is clearance of
      extracellular fluid from this material to re-establish homeostasis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7508677
TI  - Regulation of cerebral blood flow--a brief review.
AB  - Cerebral blood flow is largely independent of perfusion pressure when
      autoregulation is intact. Cerebral circulation is regulated mainly by changes of
      vascular resistance. Resistance can be modulated by local-chemical and
      endothelial factors, by autacoids, and by release of transmitters from
      perivascular nerves. Local-chemical factors such as H(+)-, K(+)-, Ca(2+)-ions,
      adenosine, and osmolarity are involved in the regulation of cerebrovascular
      resistance during cortical activation and under pathological conditions such as
      hypoxia or ischaemia. Endothelial factors such as thromboxane A2, endothelin
      (ET), endothelium derived constrictor factor and endothelium derived relaxing
      (EDRF, identified as nitric oxide, NO) or hyperpolarizing (EDHF) factor, and
      prostacyclin (PGI2), can be released by physical stimuli such as shear stress or
      haemorrhage, by autacoids, by neurotransmitters, and by cytokines. Several of
      these factors (NO, PGI2, ET) can also be released from neurons and astrocytes
      thus enabling a coupling between parenchymal function and flow. Autacoids like
      histamine, bradykinin, eicosanoids, and free radicals influence cerebrovascular
      resistance, capacitance vessels and the permeability of the blood-brain barrier
      under pathological conditions. They are released by trauma, ischaemia, seizures
      and inflammation. Cerebral arteries are innervated by several systems. The
      sympathetic-noradrenergic fibres originate from the superior cervical ganglion.
      By releasing the constricting transmitters norepinephrine and neuropeptide Y this
      system extends the range of autoregulation. The parasympathetic cholinergic
      system with the dilating transmitters acetylcholine and vasoactive intestinal
      polypeptide may prevent ischaemia. Besides the intracerebral noradrenergic and
      serotonergic perivascular innervation with an unclear function, a trigeminal
      innervation has been described.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508678
TI  - Studies of enteric pathogens and gamma-globulin levels of neonatal calves in
      Sweden.
AB  - Faecal and blood samples were taken from 10-30% of calves, 36 hours to 14 days
      old, in 47 dairy herds in different regions of Sweden from September 1987 to
      October 1988 (Olsson et al. 1993). Faecal samples from 279 calves were analysed
      for the presence of Escherichia coli (K99+), rotavirus and Cryptosporidium sp.
      Twenty (7.2%) of these samples were from diarrhoeic calves. An ELISA was
      developed and used for the rotavirus analysis. E. coli K99+ was detected in
      11.5%, Cryptosporidium sp. in 6.1% and rotavirus in 5.4% of the faecal samples.
      The presence of rotavirus alone and the combination rotavirus and E. coli (K99+)
      was found to be associated with diarrhoea (p < 0.001 and p < 0.01 respectively).
      Blood samples from 327 calves were analysed for the level of total protein and
      gamma-globulin. In 43 of these samples (13%) gamma-globulin did not separate from
      the beta 2-region by electrophoresis. The mean total protein concentration was
      53.6 g/l in calves free from diarrhoea. The mean gamma-globulin concentration,
      adjusted to 7 days age was 5.9 g/l. The 20 diarrhoeic calves had lower levels of
      both total protein and gamma-globulin, compared with calves without diarrhoea,
      but the difference was not significant. One litre more of colostrum at the first
      feed increased the level of total protein of the calves' sera by 1.4 g/l (p =
      0.05). Calves born between May and September had a 2.0 g/l higher (p < 0.001)
      serum concentration of gamma-globulin than calves born between October and April.

PMID- 7508679
TI  - Immunomodulation in the treatment of malignant disorders.
AB  - In this study, 91 patients with metastatic solid tumor were treated with an
      immunomodulatory regimen of interferons -a and -g as well as octreide in pulse
      administration, followed in selected patients by low dose perilymphatic
      administration of interleukin-2. Pharmacosensitivity studies of patient tumor
      directed concomitant chemotherapy. High levels of circulating interferon-a (> 50
      IU/ml) and the presence of lymphokine inhibitor factor were identified prior to
      treatment. None of the patients was able to produce autologous interferon. All
      patients had been previously treated with surgery and/or radiation therapy and/or
      chemotherapy. Patients had also received second line chemotherapy and/or
      radiotherapy per current protocols. At 30 days following immunomodulatory
      therapy, 6/91 patients were in complete remission; 12/91 were in partial
      remission; six patients progressed. At 180 days, with concomitant stem cell assay
      directed chemotherapy, 24/91 patients were in complete remission; 36/91
      demonstrated a partial remission. Six patients progressed. Responders
      demonstrated a fall in circulating interferon levels as well as lymphokine
      inhibitor factor concomitantly with reduction in tumor burden. NK cell activity
      increased. Marrow studies demonstrated rises in granulocyte and thrombocyte stem
      cell activity. Macrophage activity also increased. The rationale for the approach
      is discussed.

PMID- 7508680
TI  - Bone formation markers and pain palliation in bone metastases treated with
      strontium-89.
AB  - In several bone disorders, including those with metastatic involvement, changes
      in procollagen type I C-terminal and type III N-terminal peptides are detected,
      as indications of altered bone metabolism. Assessment of bone turnover could play
      a role in the evaluation of response to Strontium-89 used as palliative treatment
      in symptomatic bone metastases from various primary tumors. A correlation between
      bone formation rate markers procollagen I and III and efficacy of ionic Strontium
      89 was shown in a group of 13 patients who underwent treatment with 4 mCi of
      Strontium-89 for painful bone metastases: 5 from breast, 7 from prostate, and 1
      from lung carcinoid cancer. Assessed as a modification of analgesic intake, pain,
      and ambulation, there were 6 complete remissions, 3 partial remissions, and 4
      nonresponders. The duration of the response was from 2 to 11 months. Procollagen
      I and III levels were found to be highly abnormal in those with no benefit from
      Strontium-89 administration but were in the normal range or only slightly
      elevated in those achieving complete or partial pain control, thus correlating
      with the clinical response.

PMID- 7508681
TI  - Arsenic poisoning in central Kentucky: a case report.
AB  - A recent case of chronic arsenic intoxication due to prolonged accidental
      ingestion of a commercially available crabgrass killer illustrates one of the
      more common etiologies of present day arsenic poisoning. A review of 20 years of
      arsenic poisoning at the University of Kentucky (21 cases) revealed no cases
      attributable to an industrial source. A tabulation of the 21 most recent cases is
      included.

PMID- 7508682
TI  - New immunohistochemical "sandwich" staining method for mdr1 P-glycoprotein
      detection with JSB-1 monoclonal antibody in formalin-fixed, paraffin-embedded
      human tissues.
AB  - We have developed a new immunoperoxidase "sandwich" staining method for amplified
      detection of P-glycoprotein (Pgp) that is suitable for use on formalin-fixed,
      paraffin-embedded (conventional) tissue sections. This was accomplished by
      substantially changing the procedure described by Chan (1988) so as to increase
      specific staining intensity and to decrease nonspecific background staining. To
      determine the most appropriate primary antibody for the assay, we compared the
      immunoreactivity of JSB-1, C494, and C219 monoclonal antibodies recognizing
      internal epitopes of Pgp, and MRK16 and 4E3 monoclonal antibodies recognizing
      external epitopes of Pgp. Paraffin sections of Pgp-positive normal human tissues
      (adrenal, liver, kidney, and brain), of renal tumors, and of cell pellets of
      sensitive and multidrug resistant human tumor cell lines (MCF-7, KB) were used
      for comparisons. Immunostaining was excellent with JSB-1, moderate with C494, and
      very weak with C219. MRK16 and 4E3 showed no reaction. Nonspecific background
      staining was reduced by 1) omitting immunoglobulin G from secondary antibodies;
      2) decreasing the concentration of peroxidase-antiperoxidase complex; and 3)
      utilizing casein solution for blocking and washing. Pretreatment of sections
      before immunostaining was also simplified. Using JSB-1, the threshold for
      detection of elevated Pgp corresponded to less than two-fold relative resistance
      to doxorubicin. Applying this method, we found two of 26 non-small cell lung
      cancers were positive for Pgp, consistent with previous results of others using
      frozen sections. This new immunoperoxidase sandwich staining method using JSB-1
      now allows reliable Pgp detection in sections of formalin-fixed, paraffin
      embedded (archived) surgical specimens and small biopsy materials commonly used
      for diagnostic purposes.

PMID- 7508683
TI  - Exuberant endothelial cell growth and elements of inflammation are present in
      plexiform lesions of pulmonary hypertension.
AB  - The plexiform lesion in primary pulmonary hypertension is a glomeruloid structure
      forming channels in branches of the pulmonary artery. These lesions have been
      considered an abnormal growth of modified smooth muscle cells. We present
      immunohistochemical evidence in 10 cases of plexogenic pulmonary hypertension
      that the plexiform channels and the concentric obliterative arteriopathy
      associated with these channels represent abnormal growth of factor VIII-related
      antigen-positive endothelial cells. In addition, these cells strongly expressed
      vimentin, a growth- and differentiation-related intermediate filament.
      Morphologically and immunohistochemically, the lesions resembled the
      neovascularization associated with the brain tumor glioblastoma multiform.
      Furthermore, we noted an exclusively perivascular inflammatory cell infiltrate
      (but no vasculitis) in seven of the 10 cases with plexogenic arteriopathy
      composed of T cells, B cells, and macrophages. Our findings indicate that the
      plexiform lesion may result from a deregulated growth of endothelial cells. The
      presence of perivascular inflammatory cells suggested that cytokines and growth
      factors may further influence the development of the plexiform lesion.

PMID- 7508684
TI  - The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing
      apoptosis.
AB  - Stem cell factor (SCF) and its receptor (SCFR), a member of the receptor tyrosine
      kinase III family that is encoded by the c-kit gene, critically regulate several
      complex biological programs including hematopoiesis, mast cell development,
      cutaneous pigmentation, and gametogenesis. We show herein that mouse mast cells
      die rapidly after the withdrawal of SCF in vivo or in vitro, and provide
      morphological evidence that such mast cells undergo programmed cell death or
      apoptosis. We also show that when in vitro-derived mouse mast cells maintained in
      SCF are removed from SCF-containing medium for only 5 or 6 hours, the cells'
      genomic DNA exhibits the ladder-like pattern of oligonucleosome-sized fragments
      typical of apoptosis. These findings demonstrate that SCF can regulate the
      survival of a cellular lineage which expresses the SCFR by suppressing apoptosis.
      They also identify a mechanism that can result in striking and rapid reductions
      in the size of tissue mast cell populations without histological evidence of the
      concomitant induction of a significant inflammatory response.

PMID- 7508685
TI  - Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor
      related protein and the 39-kd receptor-associated protein in human trophoblasts.
AB  - The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related
      protein (alpha 2MR/LRP) and its 39-kd receptor-associated protein (RAP) were
      identified by indirect immunofluorescence in human extravillous and villous
      trophoblast cells at different stages of pregnancy. The alpha 2MR/LRP was
      detected in invading trophoblast cells and in some instances these invading cells
      did not express RAP. In chorionic villi of first and second trimester placenta,
      alpha 2MR/LRP and RAP were found in cytotrophoblast and syncytiotrophoblast. With
      advancing pregnancy alpha 2MR/LRP became primarily localized to the apical
      surface of the syncytiotrophoblast, while RAP was present in the cytoplasm.
      Villous cytotrophoblast cells lost both proteins by the third trimester. Isolated
      cytotrophoblast cells that undergo spontaneous differentiation into
      syncytiotrophoblast in culture increased expression of both alpha 2MR/LRP and
      RAP. With syncytium formation, alpha 2MR/LRP became localized to the plasma
      membrane in cup-like structures. Changes in the mRNAs for alpha 2MR/LRP and RAP
      paralleled the changes in relative abundance of the proteins assessed by
      immunofluorescence. cAMP treatment suppressed both alpha 2MR/LRP and RAP in the
      cultured trophoblasts, but alpha 2MR/LRP was reduced to a greater extent than
      RAP. We conclude that alpha 2MR/LRP and RAP are developmentally regulated in
      human trophoblast cells, that the temporal and spatial patterns of expression of
      these proteins can be dissociated, and that cAMP modulates both alpha 2MR/LRP and
      RAP in human trophoblast. The patterns of alpha 2MR/LRP and RAP expression in
      trophoblast cells are consistent with roles for the receptor in trophoblast
      invasion and transport of molecules across the syncytiotrophoblast.

PMID- 7508687
TI  - Pancreatic cancer palliation: using tumor stage to select appropriate operation.
AB  - To assess the effect of tumor stage on the surgical palliation of pancreatic
      cancer, 350 cancers from 74 U.S. Department of Veterans Affairs (DVA) hospitals
      from 1987 to 1991 were staged from pathologic and operative data, then grouped by
      initial surgery: biliary bypass only (BO), gastric bypass only (GO), or combined
      biliary and gastric bypass (BG). Re-operations were recorded as later gastric
      and/or biliary bypass: Stages I-II (local disease): BO (n = 52)--6 later gastric
      (12%), 3 later biliary (6%); BG (n = 60)--3 later gastric (5%); 3 later biliary
      (5%). Stage III (positive nodes): BO (n = 26)--1 later gastric (4%); BG (n = 35)-
      1 later gastrobiliary bypass (3%). Stage IV (metastases): BO (n = 71)--3 later
      gastric (4%), 3 later biliary (4%); BG (n = 70)--2 later gastrobiliary bypass
      (3%). GO (all stages): (n = 41)--1 later gastric (2%), 4 later biliary (10%).
      Using a two-factor ANOVA comparing survival by stage and original surgery, we
      found that stage had a significant effect on survival (p = 0.0001), but the type
      of initial bypass operation had no effect. Re-operation after palliative
      pancreatic cancer surgery was necessary in less than 5% of patients with BG.
      Initial BG reduced the incidence of re-operation for patients with jaundice and
      without metastatic disease, and may also benefit patients with gastric
      obstruction alone. Patients with jaundice who have peritoneal or liver metastases
      can be treated effectively with BO if they have no symptoms of gastric outlet
      obstruction.

PMID- 7508686
TI  - Induction of interleukin-8 synthesis from monocytes by human C5a anaphylatoxin.
AB  - Interleukin-8 (IL-8) is an important mediator of inflammation and has been shown
      to be a potent chemotactic/cell activator for polymorphonuclear neutrophils
      (PMNs). T lymphocytes, and basophils. Cellular sources of IL-8 include monocytes,
      PMNs, endothelial cells, epithelial cells, and keratinocytes when stimulated by
      factors such as lipopolysaccharide, IL-1, and tumor necrosis factor-alpha. This
      report demonstrates that C5a, in addition to being a direct mediator of
      inflammation, can induce both IL-8 synthesis and high levels of release from
      monocytes. Natural human C5a and a synthetic C-terminal analogue peptide of C5a
      each induced IL-8 synthesis and release from CD14+ human peripheral blood
      mononuclear cells. Antigenic reactivity based on enzyme-linked immunosorbent
      assay gave evidence that IL-8 was present in the culture supernatants of
      stimulated peripheral blood mononuclear cells. Proof that supernatant levels of
      IL-8 attain biologically significant quantities was provided by human PMN
      chemotaxis assays. The quantity of IL-8 recovered from C5a-activated monocytes in
      peripheral blood mononuclear cells is up to 1,000-fold greater than that released
      from comparable numbers of PMNs under similar conditions. Therefore, IL-8
      released from C5a-activated monocytes may play a significant role in expanding
      and prolonging cellular infiltration and activation at sites of infection,
      inflammation, or tissue injury. This observation suggests an important humoral
      amplification loop for inflammatory events involving both complement activation
      and cytokine release.

PMID- 7508688
TI  - Beta-S gene cluster haplotypes modulate hematologic and hemorheologic expression
      in sickle cell anemia. Use in predicting clinical severity.
AB  - PURPOSE: The rate of progression of major organ failure in sickle cell anemia is
      genetically controlled. It is the direct consequence of the sickle cell-evoked
      vasculopathy. PATIENTS AND METHODS: Presence of the beta S gene cluster
      haplotypes and alpha gene deletions as genetic markers indicate the expected
      frequency of illness and the risk of end-stage major organ failure. The risk of
      irreversible soft tissue organ failure is greatest in patients with a Central
      African Republic (CAR) chromosome, whereas morbidity is consistently lowest in
      patients with a Senegalese chromosome. Presence of alpha-thalassemia-2 decreases
      the risk of soft tissue organ failure in all haplotype combinations. RESULTS:
      Other laboratory abnormalities, when combined with haplotype and alpha gene
      status, also predict the risk of clinical morbidity. The mean hemoglobin level
      (or red blood cell count) is lowest in patients with the most severe clinical
      manifestations. On the other hand, the platelet count and leukocyte count as well
      as the plasma fibrinogen level are elevated in the sickest patients. A threshold
      level of hemoglobin F at 1.2 g/dl (approximately 20% hemoglobin F) decreases the
      risk of major organ failure and is attained most frequently in those with a
      Senegalese chromosome. Hemorheologic findings observed during the most stable
      state of patients with sickle cell anemia indicate two trends: (a) the mean
      percentage of dense red cells is nearly twice as high in the maximal severity
      patients as compared with the minimal severity patients; and (b) mean red cell
      rigidity is greatest in the maximal severity group and least in the minimal
      severity group. These findings suggest that a greater percentage of dense, poorly
      deformable red cells are present in sickle cell patients in the genotypic
      category of maximal severity. CONCLUSIONS: The combination of the beta S gene
      cluster haplotype and alpha-gene status correlates with both phenotypic
      laboratory findings (hematologic profile) and morbidity. These associations
      increase our ability to predict clinical severity and the future risk of major
      organ failure.

PMID- 7508689
TI  - Experimental therapy of sickle cell disease. Use of hydroxyurea.
AB  - PURPOSE: Therapy of sickle cell disease with hydroxyurea is experimental.
      PATIENTS AND METHODS: We have begun a randomized blinded clinical trial to
      determine its clinical utility. The efficacy of this drug is unproved and its
      risks, which include mutagenesis, teratogenesis and carcinogenesis, are poorly
      understood. These risks are explicitly stated in our consent forms. A significant
      number of patients who are asked to enroll refuse to enter the study. This
      refusal is probably because of individual variations in perception of risk and
      personal inconvenience, as well as differences in perception of personal benefit.
      We have a few hints as to which patients are more likely to produce increased
      amounts of fetal hemoglobin, but our findings do not indicate which patients are
      most likely to show a good clinical response. RESULTS: Our study group decided
      not to treat patients under 18 years of age with hydroxyurea until clinical
      efficacy of the drug is proved in adults. We have criteria for selecting patients
      for entry into our ongoing study, but the criteria are based more on study design
      than on an estimate of present or future severity of the manifestations of sickle
      cell disease. CONCLUSIONS: Features of our previous study and results of the
      present trial may be helpful in defining indications for bone marrow
      transplantation in children with sickle cell disease.

PMID- 7508690
TI  - Butyrate derivatives. New agents for stimulating fetal globin production in the
      beta-globin disorders.
AB  - PURPOSE: Stimulating expression of the normal fetal globin genes is a preferred
      method of ameliorating sickle cell disease and beta-thalassemia for the majority
      of patients in North America who do not have appropriate bone marrow donors.
      PATIENTS AND METHODS: Due to increased survival of red blood cells that contain
      both hemoglobin S and hemoglobin F, as little as 4-8% fetal globin synthesis in
      the bone marrow can produce levels of hemoglobin F of approximately 20% in the
      peripheral circulation. Some success has been achieved in stimulating hemoglobin
      F using chemotherapeutic agents (such as hydroxyurea and 5-azacytidine) and
      growth factors (erythropoietin) that alter erythroid growth kinetics. However,
      there is reluctance to treat children with chemotherapeutic agents because of
      possible undesirable long-term side effects. RESULTS: Butyric acid and butyrate
      derivatives are generally safe compounds that stimulate the promoters of
      individual fetal and embryonic globin genes and thus provide a more specific
      therapy. An initial trial with the parent compound, given as arginine butyrate,
      has demonstrated rapid stimulation of fetal globin expression to levels that can
      ameliorate these conditions. Phase I trials of an oral butyrate derivative with a
      long plasma half-life have begun. CONCLUSIONS: These agents may provide a new and
      specific approach for ameliorating the clinical manifestations of sickle cell
      disease and beta-thalassemia.

PMID- 7508691
TI  - Propofol and intralipid cause creaming of serum from critically ill patients.
AB  - The aim of this in-vitro study was to investigate the incidence of propofol
      agglutination with serum from critically ill patients. Serum (400 microliters)
      from 58 critically ill patients and 30 healthy volunteers was incubated with 10
      microliters of either propofol, Intralipid 10% or Intralipid 20%. Control
      incubations contained serum only. At 24 h, the serum was examined macroscopically
      and microscopically for agglutination. Agglutination was seen with Intralipid 20%
      in serum from all critically ill patients and 13.3% of volunteers. Serum from
      91.4% of critically ill patients was agglutinated with Intralipid 10% and only
      3.3% of the healthy volunteers. In comparison, propofol produced agglutination in
      74.1% of critically ill patients and in none of the serum from healthy volunteers
      (p < 0.05 propofol versus Intralipid 10%, p < 0.0001 propofol versus Intralipid
      20%). No correlation was seen between agglutination and age, sex, APACHE II score
      or plasma concentration of acute phase proteins. However, agglutination of
      propofol and Intralipid 10% was more frequent (p < 0.001) in serum from patients
      with pulmonary disease, than in patients with normal lungs. The clinical
      implications of these in-vitro findings are unclear and need further
      investigation.

PMID- 7508692
TI  - Histamine release following atracurium in the elderly.

PMID- 7508693
TI  - Jet ring cell: a tool for flow injection spectroscopy and microscopy on a
      renewable solid support.
AB  - A new flow cell design for spectroscopic measurements of suspensions, the jet
      ring cell, is introduced. This cell exploits radial flow through a narrow ring
      shaped gap to retain suspended particles within the detection region. This ring
      constitutes a detection volume of well-defined area from which the trapped
      particles can be instantaneously removed at will. The bed of particles thus forms
      a renewable surface, which can be probed by reflectance, fluorescence, or
      chemiluminescence using a microscope or optical fiber. This device should prove
      useful for microscopic study of cells, for automated immunoassays, and for
      preconcentration of analytes on sorbents with in situ spectroscopic detection. In
      conjunction with a fiber optic detection system, the jet ring cell becomes a
      component of a renewable chemical sensor system.

PMID- 7508694
TI  - Thin gold film-assisted laser desorption/ionization Fourier transform ion
      cyclotron resonance mass spectrometry of biomolecules.
AB  - A new thin gold film-assisted (TGFA) laser desorption/ionization (LDI) technique
      has been combined with Fourier transform ion cyclotron resonance (FT-ICR) high
      resolution mass analysis. A thermally labile organic sample is coated onto a thin
      gold film deposited on a glass plate and desorbed and ionized by Nd:YAG laser
      irradiation. The wavelength for maximum light absorption may be tuned by varying
      the thickness of the metal film; e.g., a 10-nm-thick gold film absorbs maximally
      near the Nd:YAG fundamental wavelength (1064 nm). A key advantage of the method
      is the stability of the gold film, which facilitates deposition of samples from
      any of a variety of solvent systems. Coupled with recently introduced quadrupolar
      excitation and collisional cooling for ion axialization, TGFA-LDI FT-ICR mass
      spectra provide high sensitivity (e.g., 100-fmol single-shot detection limit and
      mass resolving power, m/delta m approximately 113,000, for (M+K)+ ions from
      gramicidin S at m/z 1180).

PMID- 7508695
TI  - Hyaluronic acid and hyaluronic acid-binding proteins in brain extracellular
      matrix.
AB  - Hyaluronic acid (HA) plays the main structural role in the formation of brain
      extracellular matrix (ECM). The extracellular space appears empty by electron
      microscopy because HA is readily dissolved during the preparation of tissues for
      ultrastructural studies. The HA-binding proteins so far identified in brain ECM
      are versican, aggrecan and the glial HA-binding protein. Versican is a large
      fibroblast proteoglycan preferentially expressed in embryonic cartilage at the
      time of mesenchymal condensation. Glial HA-binding protein (GHAP) is probably a
      proteolytic product of versican corresponding to its HA-binding amino-terminal
      domain. It is mainly a white-matter protein, suggesting that the proteinase
      responsible for its cleavage from versican is normally activated in this
      location. Versican is found in both white matter and gray matter, where it forms
      pericellular coats around large neurons. Aggrecan, the aggregating proteoglycan
      of mature cartilage, co-localizes with versican in this location. In white
      matter, the localization of GHAP and versican is identical to that of the glial
      fibrillary acid protein, suggesting that both proteins are produced by
      astrocytes. An important difference between GHAP and versican is that GHAP but
      not versican is released from the tissues by hyaluronidase digestion, which
      suggests that versican is anchored to the cell membranes lining the extracellular
      space. GHAP was localized at the ultrastructural level in the granule cell layer
      of rat cerebellum, the only region of gray matter that is positive for GHAP in
      this species. Rats were perfused with aqueous fixatives containing
      cetylpyridinium chloride or tannic acid to prevent the solubilization of HA. GHAP
      is found throughout the extracellular space, the synaptic clefts being a notable
      exception. GHAP appears late in development, and the same is true for versican,
      the characteristic perineuronal coats first becoming apparent in the third
      postnatal week. It is suggested that a marked change occurs in the structure of
      brain ECM when HA-binding proteins first appear, and that the change is similar
      to that observed in prechondrogenic mesenchyme, i.e., reduction of the
      extracellular space and cell aggregation.

PMID- 7508696
TI  - Colocalization of tenascin with versican, a hyaluronate-binding chondroitin
      sulfate proteoglycan.
AB  - Rabbit antisera against tenascin, a large extracellular matrix protein, in
      conjunction with monoclonal antibodies of mouse origin against versican, a large
      hyaluronate-binding proteoglycan, were used to make a comparative study of the
      distribution of the two antigens in the same cryostat sections by double
      immunofluorescence. In the central nervous system, tenascin was invariably
      associated with versican, but the reverse was not true, in that versican was also
      found where tenascin was not detectable, particularly in gray matter. There were
      major species differences in the distribution of tenascin in the central nervous
      system. In the cow, tenascin was found in cerebral and spinal cord white matter
      and in the granule cell layer of the cerebellum. In the human brain, tenascin was
      found in cerebral white matter but not in the cerebellum. In the rat, tenascin
      was mainly confined to brain periventricular layer and spinal cord white matter.
      During the development of the cerebellum of the rat, the tenascin
      immunoreactivity decreased, and a lower molecular weight band appeared (J1
      160/180/restrictin?) and persisted throughout adulthood. Tenascin expression was
      a relatively late event in the development of the rat central nervous system,
      immunoreactivity being first observed after birth. In the rat embryo, tenascin
      was found to co-localize with versican in precartilaginous mesenchyme and in
      connective tissue underlying epithelia. The colocalization of versican with
      tenascin suggests that versican may be the tenascin (cytotactin)-associated
      proteoglycan reported in the literature.

PMID- 7508697
TI  - Determination of the hemodynamics and histamine release of rocuronium (Org 9426)
      when administered in increased doses under N2O/O2-sufentanil anesthesia.
AB  - The cardiovascular effects, histamine release potential, and pharmacodynamics of
      rocuronium were determined in adult patients randomized to receive rapid (5 s)
      intravenous (i.v.) bolus doses of 600, 900, or 1200 micrograms/kg (2.0, 3.0, and
      4.0 times the ED95) with maintenance doses of 150 micrograms/kg. There were no
      statistically significant hemodynamic effects (heart rate, blood pressure, mean
      arterial pressure [MAP] or electrocardiogram [ECG]) after administration of
      rocuronium. There were no increases in plasma histamine levels at 1, 3, and 5 min
      after the rapid i.v. bolus of rocuronium as determined by a new radioimmunoassay
      (RIA) with a sensitivity for histamine quantification of 0.05 ng/mL. Endotracheal
      intubation was successfully performed 6 min after rocuronium administration (and
      after plasma samples were obtained). The mean +/- SD clinical durations of 600-,
      900-, and 1200-micrograms/kg intubating doses of rocuronium under N2O/O2
      sufentanil anesthesia were 45 +/- 20 min, 66 +/- 16 min, and 85 +/- 22 min,
      respectively. We conclude that rocuronium can be administered safely over a wide
      range of doses (2-4 x ED95), with minimum hemodynamic effects or histamine
      release.

PMID- 7508698
TI  - Activation of the cortical and medullary dopaminergic systems by nitrous oxide in
      rats: a possible neurochemical basis for psychotropic effects and postanesthetic
      nausea and vomiting.
AB  - To provide a neurochemical basis for the central nervous system actions of
      nitrous oxide, the changes of brain dopamine (DA), serotonin (5-HT),
      norepinephrine (NE), and metabolites of DA and 5-HT were studied in rats. Thirty
      male Wistar rats were assigned to one of five groups according to the type of gas
      and the duration of gas exposure. The rats in one group, which served as control,
      were exposed to air for 30 min, and the rats in four other groups were exposed to
      75% nitrous oxide in oxygen for 0.5, 1, 2, and 4 h, respectively. Animals were
      killed with microwave irradiation, and the brains were divided into seven
      sections: the cerebral cortex, cerebellum, striatum, hippocampus, midbrain
      thalamus, hypothalamus, and medulla-pons. The contents of NE, DA, 3,4
      dihydroxyphenyl-alanine (DOPAC), homovanillic acid (HVA), 5-HT, and 5
      hydroxyindoleacetic acid (5-HIAA) in each discrete area were measured with high
      performance liquid chromatography. Nitrous oxide had no significant effect on the
      contents of NE, 5-HT, nor 5-HIAA, but decreased that of DA in the striatum and
      midbrain-thalamus after 4 h of exposure (P < 0.05). Levels of DOPAC, but not DA,
      in the cerebral cortex and medulla-pons were increased significantly at exposures
      up to 2 h (P < 0.05), but were not significant from control levels after a 4-h
      exposure. Increased levels of DOPAC indicate that nitrous oxide increases
      dopaminergic neuronal activities in the mesocortical projection and the medullary
      network.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508699
TI  - Molecular mechanism of anesthesia: another voice.

PMID- 7508700
TI  - [Acute respiratory distress caused by a mediastinal pancreatic pseudocyst].
AB  - The pseudocyst of the pancreas is a frequent complication of acute pancreatitis.
      However to intrathoracic localization remains exceptional. A case of acute
      respiratory insufficiency in a 66-year-old man in whom artificial ventilation was
      required for such a complication is reported. This case stresses the difficulty
      often encountered for the differential diagnosis of these liquid tumors. The
      clinical signs are variable and non specific, especially in case of absence of
      any history of pancreatitis. The radiographic studies, in particular
      ultrasonography and CT-scanner defines its liquid nature and its connections.
      Endoscopy examination confirms its retro-oesophageal extension due to the
      migration through the oesophageal hiatus. Only the percutaneous needle aspiration
      of a collection or an associated pleural effusion confirms the diagnosis by the
      high content of amylases. The treatment of this type of localisation is surgical
      and essentially consists of an internal derivation.

PMID- 7508701
TI  - Fetal hemoglobin and the glycosylated hemoglobin assay.

PMID- 7508702
TI  - Histocytochemistry of glycoconjugates in nasal inverted papilloma.
AB  - In order to investigate the changes in cellular distribution of the glycocalyces
      in nasal inverted papilloma, formalin-fixed, paraffin-embedded biopsy specimens
      of inverted papilloma were analyzed by the avidin-biotin-peroxidase complex
      technique for the demonstration of peanut agglutinin (PNA) receptors,
      concanavalin A (Canavalia ensiformis agglutinin; ConA) receptors,
      carcinoembryonic antigen (CEA), and keratin, and compared with normal nasal
      mucosa, nasal polyps, and papillary adenocarcinoma. The inverted papillomas were
      positive for PNA and CEA, to the same degree as papillary adenocarcinoma. Their
      PNA binding was related to the degree of dysplasia. The ConA reaction was
      intermediate between that of normal mucosa and adenocarcinoma. The results
      suggest that the alteration of cellular glycoprotein structure in inverted
      papilloma is associated with its biologic characterization.

PMID- 7508703
TI  - Distribution of cytokeratins in the vestibular epithelium of the guinea pig.
AB  - Cytokeratin expression in the vestibular labyrinth of the guinea pig was
      investigated with immunofluorescence and immunoperoxidase staining on surface
      preparations of the vestibular epithelium. Phalloidin, an F-actin-specific probe,
      was used to distinguish between hair cells and supporting cells. Cytokeratin
      expression was not found in the cytoplasmic domain of hair cells of the crista
      ampullaris, utricle, or saccule. Cytokeratin expression was abundant in
      supporting cells of the vestibular sensory epithelium. Electron microscopy
      revealed the presence of desmosomes, which are associated with cytokeratins,
      within type 2 hair cells of the vestibular epithelium. It appears that
      cytokeratins are absent within the cytoplasmic domain of hair cells, but are
      present in association with intercellular junctions. The functional significance
      of this unique pattern of cytokeratin expression within the vestibular epithelium
      is discussed.

PMID- 7508704
TI  - Palliative fever management in Alzheimer patients. quality plus fiscal
      responsibility.
AB  - Aggressive medical treatment of infections does not affect the progressive course
      of dementia of the Alzheimer type (DAT) and has limited effect on the mortality
      rate. Utilization of health care resources and discomfort during a fever episode
      were compared in three differing treatment conditions: in 18 patients in a
      dementia special care unit (DSCU) who received palliative management, 26 patients
      in a DSCU who were treated aggressively, and 17 DAT patients in traditional long
      term care units who were treated aggressively. Both groups of patients in the
      DSCU had lower discomfort scores, lower utilization of high-cost health care
      resources, and higher utilization of analgesics and narcotics. A nursing model of
      care incorporating hospice concepts into the DSCU is suggested.

PMID- 7508705
TI  - Feminist critique: searching for meaning in research.
AB  - Feminist critique is presented as an important method for examination of prior
      knowledge for androcentric and ethnocentric bias in all aspects of knowledge
      development, from theoretical underpinnings through the steps of the research
      process. The history and implications for using feminist critique as a mode of
      inquiry for nursing science are developed. In addition, pragmatic information for
      the conduct of feminist critique is provided.

PMID- 7508706
TI  - Interpretive research methodology: broadening the dialogue.
AB  - This article expands the dialogue on interpretive research methodology, locating
      this set of approaches within a broad historical and interdisciplinary context.
      Several of the most commonly held misconceptions in nursing, particularly those
      related to the meanings and derivations ascribed to "grounded theory," "symbolic
      interactionism," and "ethnography," are examined. The interpretive research
      approaches not only have gained broader acceptance across disciplines, but also
      have shifted in more radical and often less structured directions during the past
      decade. Several pivotal areas of these ongoing shifts are analyzed for their
      relevance to nursing research: the influence of critical and feminist theory and
      postmodernism, the ambiguity inherent in both every-day life and the research
      enterprise, the importance of locating the researcher, power and status
      inequities, the problematic aspects of language, meaning, and representation, and
      the emphasis on reflexivity and context as constitutive of meaning.

PMID- 7508707
TI  - Oxidative damage of mitochondria induced by Fe(II)citrate is potentiated by Ca2+
      and includes lipid peroxidation and alterations in membrane proteins.
AB  - Isolated rat liver mitochondria exposed to Fe(II)citrate undergo lipid
      peroxidation and alterations in membrane proteins. These processes were
      associated with irreversible decrease in membrane potential and mitochondrial
      swelling. Lipid peroxidation was evidenced by the production of thiobarbituric
      acid-reactive substances and also by the reaction of these products with membrane
      proteins, through the formation of Schiff bases. Alterations in membrane proteins
      were also characterized by the loss of specific proteins that could be recovered
      from the mitochondrial supernatant as shown by SDS-polyacrylamide gel
      electrophoresis. The degree of both lipid peroxidation and alterations in
      membrane proteins were diminished by EGTA, ruthenium red, or dibucaine. This
      strongly indicates that Ca2+ potentiates the oxidative damage of mitochondria
      exposed to Fe(II)citrate.

PMID- 7508708
TI  - Elevated expression of the Cyp1a2 gene in the presence of nicotinamide by adult
      mouse hepatocytes in primary culture.
AB  - Effects of nicotinamide on expression of Cyp1a1 and Cyp1a2 genes were
      investigated in adult C57BL/6NCrj mouse hepatocytes in primary culture. The cells
      were cultivated for up to 8 days as monolayers or spheroids (multicellular
      aggregates), respectively, on collagen-coated or noncoated dishes. CYP1A1 mRNA
      was prominently induced after exposure to 3-methylcholanthrene (MCA) throughout
      the observation period with either type of culture. In monolayer-cultured cells,
      substantial induction of CYP1A2 mRNA by MCA was observed only at day 1 of
      cultivation, followed by a decrease to very low levels thereafter. In contrast,
      prominent elevation of both mRNA species in spheroid culture was observed
      throughout the 8-day experimental period. In the presence of nicotinamide, the
      decrease in expression of CYP1A2 mRNA in monolayer-cultured hepatocytes was
      restored concentration-dependently and at 10 mM nicotinamide the induced amounts
      were equivalent to those observed in spheroid cells. Nicotinamide also elevated
      CYP1A2 mRNA expression in spheroid culture, but in both cases induction of CYP1A1
      mRNA decreased. Constitutive expression of CYP1A2 mRNA in monolayer culture
      rapidly decreased with increasing culture period, but addition of nicotinamide
      likewise inhibited the decrease. Nicotinamide also restored considerable
      expression of CYP1A2 mRNA when not present from the start of cultivation, but
      added 24 h before. Activities of aryl hydrocarbon hydroxylase (AHH) and
      acetanilide-4-hydroxylase (AAH) were elevated with either type of culture after
      treatment with MCA and the presence of nicotinamide further increased the AAH,
      resulting in an increment in the activity ratio of AAH vs AHH. Intracellular
      contents of NAD were considerably elevated by addition of nicotinamide. However,
      isonicotinamide, which is not converted to NAD in the cell, also elevated CYP1A2
      mRNA expression prominently. Furthermore, NAD contents in spheroid culture were
      not higher than those in monolayer culture. These observations indicate that the
      presence of nicotinamide in the medium restores constitutive and inducible
      expression of Cyp1a2 gene, independent of NAD, and thus the compound is useful
      for studying the underlying mechanism of regulation of this gene in adult mouse
      hepatocytes in monolayer culture.

PMID- 7508709
TI  - Regulation of lysyl oxidase mRNA in dermal fibroblasts from normal donors and
      patients with inherited connective tissue disorders.
AB  - Lysyl oxidase (LO) is an extracellular copper-dependent enzyme that catalyzes the
      initial reaction in the formation of lysine or hydroxylysine-derived crosslinks
      during collagen biosynthesis. We have isolated a cDNA for human LO from skin
      fibroblast poly(A+)RNA by PCR using primers based on the recently published
      sequence of human LO. This cDNA probe detects a major mRNA of 4.2 kb on Northern
      blots of RNA from normal fibroblasts. The level of LO mRNA was not significantly
      affected by cell density or by ascorbate treatment. Treatment of skin fibroblasts
      with hydralazine (50 microM), which increases the mRNAs for both the alpha and
      the beta subunits of prolyl hydroxylase (PH) and the mRNAs for lysyl hydroxylase,
      also increased LO mRNA by fourfold over a 72-h time course. In contrast,
      hydralazine dramatically decreased the mRNAs for alpha 1(I) collagen.
      Administration of minoxidil (500 microM), which specifically decreases LH
      activity without affecting PH activity or collagen biosynthesis in skin
      fibroblasts, stimulated the level of LO mRNA. Neither the administration of
      penicillamine (100 microM), which interferes with collagen cross-linking, nor the
      administration of beta-aminopropionitrile, which is a strong irreversible
      inhibitor of LO, to fibroblasts significantly changed the levels of LO mRNA over
      a 72-h time course. However, bleomycin (0.6 microgram/ml) significantly decreased
      the 4.2-kb LO mRNA in contrast to the levels of the alpha 1(I) collagen mRNAs,
      which were unchanged. No significant change was observed in the steady-state
      levels of LO mRNAs in fibroblasts isolated from patients with certain connective
      tissue disorders, including Marfan syndrome, Menkes disease, cutis laxa, and
      pseudoxanthoma elasticum.

PMID- 7508710
TI  - Receptor-independent uptake of transferrin-bound iron by reticulocytes.
AB  - Under physiological conditions the uptake of transferrin-bound iron by
      reticulocytes involves transferrin binding to membrane receptors followed by
      endocytosis, release of iron from the transferrin within endosomes, and recycling
      of apotransferrin to the cell surface. However, as shown in the present work,
      iron uptake and incorporation into heme will also occur if the cells are
      incubated in low-ionic-strength media such as isotonic sucrose. This process has
      a pH optimum of 5.9, is not inhibited by inactivation of the transferrin
      receptors, and does not involve transferrin endocytosis, but is inhibited by
      addition of various salts, ferricyanide, and low concentrations of ferric iron
      chelators, including apotransferrin, to the incubation medium. Iron uptake is
      temperature dependent, has a high activation energy and is inhibited by a variety
      of metabolic inhibitors. It is also saturable with an apparent Km of
      approximately 0.2 microM transferrin-Fe. It is concluded that under these
      incubation conditions iron is released from transferrin at the external surface
      of the cell and is transported into the cell by a facilitated, possibly active,
      transport process. This may occur via the iron carrier which normally functions
      in the membrane lining of endosomes. Reduction of the iron to the ferrous state
      is probably necessary for its transport into the cell.

PMID- 7508711
TI  - [Sexual activity after surgery for benign prostatic hypertrophy].
AB  - A retrospective study was conducted in 57 patients who had undergone surgery at
      our center for benign prostatic hyperplasia over a period of one year.
      Postoperative sexual activity and the presence or absence of antegrade
      ejaculation were determined. Of these patients, 19 had no sexual activity before
      or after the operation and were therefore excluded from the study. The surgical
      techniques utilized were transvesical adenomectomy in 27 cases and TUR in 11
      cases. Three patients (8%) were impotent after surgery, the difference between
      the two surgical techniques not being statistically significant. Retrograde
      ejaculation was observed in 58% (70% of the patients who underwent open surgery
      and 27.2% of those who underwent TUR). We analyze the results reported elsewhere
      and underscore the need to conduct prospective studies on one or several
      techniques using the same terminology in order to draw more reliable conclusions.

PMID- 7508712
TI  - Plasma viscosity in giant cell arteritis.

PMID- 7508713
TI  - Use of pleural Tenckhoff catheter to palliate malignant pleural effusion.
AB  - Malignant pleural effusion and its treatment both cause substantial morbidity in
      patients with advanced neoplastic disease. We hypothesized that this morbidity
      might be ameliorated by placement of an indwelling Tenckhoff catheter into the
      involved pleural space. Catheters were placed in 9 patients under local
      anesthesia. Three patients underwent bilateral catheter placement, for a total of
      12 catheters placed. Four of the 9 patients had undergone previous unsuccessful
      pleurodesis (using tetracycline or bleomycin). Whenever it became symptomatic,
      the malignant pleural effusion was simply drained into a calibrated container and
      the volume recorded. Patients were followed on a weekly basis until their death
      (mean, 16 weeks). The mean drainage was 477 mL per 24 hours (range, 200 to 1,100
      mL). No pleural space infections occurred, although local cellulitis developed in
      3 patients around the catheter exit site; all patients responded to oral
      antibiotics. There were no significant changes in either the serum albumin or
      total protein levels. No catheters malfunctioned and no patients required further
      treatment or hospitalization for symptoms of malignant pleural effusion. We
      conclude that this technique may reduce the morbidity stemming from malignant
      pleural effusion and its treatment by allowing patients to conveniently and
      painlessly drain the effusion at home when it becomes symptomatic. This technique
      may provide superior palliation in patients with malignant pleural effusion.

PMID- 7508714
TI  - Aprotinin does not neutralize heparin.

PMID- 7508715
TI  - Immunostaining for Leu-7 in the diagnosis of thyroid carcinoma.
AB  - The morphologic distinction between benign and malignant thyroid lesions can be
      difficult. Immunostaining for the Leu-7 antigen has been reported to be useful in
      the diagnosis of thyroid carcinoma. To test the specificity of immunostaining for
      Leu-7 in the diagnosis of thyroid carcinoma, we studied formalin-fixed, paraffin
      embedded tissue specimens obtained from 66 thyroid lesions using the HNK-1
      monoclonal antibody to Leu-7 and an avidin-biotin-complex technique. Positive
      reactivity for Leu-7 was seen in 11 (33%) of 33 benign thyroid conditions and in
      27 (82%) of 33 thyroid carcinomas. We conclude that immunostaining for Leu-7 is
      not specific in the diagnosis of thyroid carcinoma.

PMID- 7508716
TI  - Levels and profiles of polycyclic aromatic hydrocarbons in the Zagreb air in the
      heating season.
AB  - Samples of suspended particulate matter, collected at four sites in Zagreb during
      the heating season were analysed for the content of polycyclic aromatic
      hydrocarbons. Data were analysed with special reference to indicators of car
      traffic contribution the BghiPer/BaP and Cor/BaP ratios. Taking 1.5 as a
      borderline value for the BghiPer/BaP ratio, a significant influence of car
      traffic on air pollution by polycyclic aromatic hydrocarbons was noticed at a
      site close to a petrol station. Our data were compared with the BghiPer/BaP and
      Cor/BaP ratios from other countries. A similar relationship of the ratios between
      urban and traffic near sites was obtained.

PMID- 7508717
TI  - Cellular distribution, subcellular localization and possible functions of basic
      and acidic fibroblast growth factors.
AB  - The distribution in the rat nervous system of acidic and basic fibroblast growth
      factors (FGFs) was analysed by a combination of biochemical and anatomical
      methods. Acidic FGF (aFGF) was found to be present exclusively in specific
      neuronal populations, such as motor neurons and basal forebrain cholinergic
      neurons. Basic FGF (bFGF) was found in astrocytes and in neurons in hippocampal
      area CA2. Within labelled astrocytes and CA2-neurons, bFGF was detected in both
      the cytoplasm and the nucleus. The levels of intracellular bFGF were manipulated
      by antisense oligonucleotide treatment of cultures of developing neural crest
      cells. Results indicated that the amount of melanogenesis in the cultures is
      likely to be regulated by intracellular, possibly nuclear bFGF.

PMID- 7508718
TI  - Epidermal growth factor induced tyrosine phosphorylation of nuclear proteins
      associated with translocation of epidermal growth factor receptor into the
      nucleus.
AB  - Treatment of human squamous carcinoma cells (HN5 cells) with epidermal growth
      factor (EGF) caused a time-dependent increase in tyrosine phosphorylation of six
      nuclear proteins of molecular mass 166, 140, 117, 95, 86 and 79 kDa. The major
      tyrosine phosphorylated protein was indistinguishable from the plasma membrane
      form of the epidermal growth factor receptor and was shown by enzyme linked
      immunosorbent assay (ELISA) to be translocated into the nucleus from extra
      nuclear sites upon ligand stimulation. Using immunoelectron microscopy of both
      isolated nuclei and whole cells, epidermal growth factor receptor (EGF-R) was
      found to be associated with the chromatin and, to a lesser extent, with the inner
      surface of the nuclear membrane. Tyrosine phosphorylation of proteins other than
      EGF-R was particularly notable in the nucleoli. These observations suggest that
      EGF-R may exert some of its physiological functions by directly inducing tyrosine
      phosphorylation of specific nuclear proteins. Translocation of EGF-R to the
      nucleus may provide a vital link between plasma membrane signalling and gene
      activation.

PMID- 7508719
TI  - Mapping of immunogenic domains on porcine zona pellucida 3 alpha and beta
      glycoproteins by murine monoclonal antibodies.
AB  - PROBLEM: Immunization with zona pellucida (ZP) leads to block in fertility with
      variable degree of ovarian dysfunctions. To design an immunocontraceptive vaccine
      based on synthetic peptides of zona pellucida, it is imperative to identify and
      define epitopes involved in sperm binding. METHOD: Epitopic domains recognized by
      monoclonal antibodies (MAbs) specific to either porcine ZP3 alpha or ZP3 beta
      glycoproteins were delineated in an enzyme-linked immunosorbent assay (ELISA)
      based on the ability of a MAb in solution to inhibit the binding of biotinylated
      ZP3 to another MAb coated on a microtitration plate. Immunoblot studies were
      carried out to determine the nature of reactive determinants. Porcine oocytes
      preincubated with MAbs were tested for sperm binding in vitro. RESULTS: Out of 23
      MAbs generated, 10 had specificity for ZP3 alpha and 13 for ZP3 beta. By using
      these antibodies, eight epitopic domains on both ZP3 alpha and ZP3 beta were
      discernible. On ZP3 beta, epitopic domain DI partially overlaps with DII and DV
      with DVI, whereas on ZP3 alpha domains DI to DV were in close proximity with a
      partial overlap, suggesting the dominance of this region. All 10 MAbs against ZP3
      alpha, and 10 out of 13 against ZP3 beta recognized deglycosylated forms of
      antigens. Seven antibodies having specificities for ZP3 alpha and ZP3 beta
      respectively recognized linear epitopes. MA-30, having specificity for ZP3 beta
      and MA-420 for ZP3 alpha and recognizing linear epitopes significantly inhibit
      the binding of boar sperm to porcine oocytes in vitro. CONCLUSIONS: Collectively,
      these studies indicate the value of utilizing MAbs for identifying and
      characterizing functionally significant ZP determinants. MAbs recognizing
      sequential epitopes will help in the elucidation of the amino acid sequence of
      the epitopes, which will subsequently help in design of synthetic
      immunocontraceptive vaccines.

PMID- 7508720
TI  - A general method for identification of polyhydroxyalkanoic acid synthase genes
      from pseudomonads belonging to the rRNA homology group I.
AB  - Using a 30-mer oligonucleotide probe highly specific for polyhydroxyalkanoic acid
      (PHA) synthase genes, the respective genes of Pseudomonas citronellolis, P.
      mendocina, Pseudomonas sp. DSM 1650 and Pseudomonas sp. GP4BH1 were cloned from
      genomic libraries in the cosmid pHC79. A 19.5-kbp and a 22.0-kbp EcoRI
      restriction fragment of P. citronellolis or Pseudomonas sp. DSM 1650,
      respectively, conferred the ability to accumulate PHA of medium-chain-length 3
      hydoxyalkanoic acids (HAMCL) from octanoate as well as from gluconate to the PHA
      negative mutant P. putida GPp104. An 11.0-kbp EcoRI fragment was cloned from P.
      mendocina, which restored in GPp104 the ability to synthesize PHA from octanoate
      but not from gluconate. From Pseudomonas sp. GP4BH1 three different genomic
      fragments encoding PHA synthases were cloned. This indicated that strain GP4BH1
      possesses three different functionally active PHA synthases. Two of these
      fragments (6.4 kbp and 3.8 kbp) encoded for a PHA synthase, preferentially
      incorporating hydroxyalkanoic acids of short chain length (HASCL), and the
      synthases were expressed in either GPp104 and Alcaligenes eutrophus H16-PHB-4,
      respectively. The PHA synthase encoded by the third fragment (6.5 kbp) led to the
      incorporation of HAMCL and was expressed in GPp104 but not in PHB-4.

PMID- 7508721
TI  - Expression cloning of the nox, mdh and ldh genes from Thermus species encoding
      NADH oxidase, malate dehydrogenase and lactate dehydrogenase.
AB  - The Thermus thermophilus HB8 mdh and ldh genes and the T. aquaticus EP00276 nox
      and mdh genes encoding the biotechnologically important enzymes NADH oxidase (EC
      1.6.99.3), malate dehydrogenase (EC 1.1.1.37) and lactate dehydrogenase (EC
      1.1.1.27) were cloned on the basis of known sequences from related species using
      the polymerase chain reaction. The nox and mdh genes were directly placed under
      the control of regulatory expression elements from Escherichia coli. When the 5'
      portions of the re-cloned nox gene and the mdh gene of T. thermophilus HB8 were
      simultaneously altered, enzyme yields of 18-42% of the total soluble cellular
      protein were obtained as compared to 2-6% obtained from the unchanged genes. The
      high overproduction level upon the alterations can be explained by the occurrence
      of additional potential base pairs between nucleotides in the mRNA downstream of
      the start codon ('downstream box') and the 16S rRNA. An 'universal translation
      initiation sequence' providing such strong interactions may be of general use for
      high overproduction levels.

PMID- 7508722
TI  - [The quality of the preservation of lungs using different solutions (an
      experimental study)].
AB  - Effects of different perfusion conditions and storage of isolated dog lungs on
      the process of edema development were studied. Sixty-nine mongrel dogs were used
      in the study. In case of a 15 min perfusion via the pulmonary artery and 12 h
      storage lung condition depended mainly on the type of solution and addition of
      protective drugs to this solution. Euro-Collins and low-potassium electrolytic
      solution markedly increased capillary hydrostatic pressure and drastically
      reduced plasma colloid-osmotic pressure. As a result filtration coefficient
      increased and as soon as an hour after reperfusion onset a marked pulmonary edema
      developed. Use of LPD solution without drugs added for 2.5 h reperfusion was
      associated with a moderate increase of capillary hydrostatic pressure and
      negligible decrease of plasma colloid-osmotic pressure. If the reperfusion were
      longer plasma colloid-osmotic pressure reduced, this leading to development of
      moderate pulmonary edema. A 15 min lung perfusion via the pulmonary artery and 12
      h storage at 1 degree C in LPD solution with membrane protectors and antioxidants
      was associated with virtually unchanged capillary hydrostatic pressure, plasma
      colloid-osmotic pressure, and filtration coefficient and, hence, no pulmonary
      edema.

PMID- 7508723
TI  - Differential antiviral activity of two TIBO derivatives against the human
      immunodeficiency and murine leukemia viruses alone and in combination with other
      anti-HIV agents.
AB  - R82913 and R86183, two derivatives of tetrahydroimidazo[4,5,1-jk][1,4]
      benzodiazepin-2(1H)-thione (TIBO), were found to potently and selectively inhibit
      the replication and cell killing effects of a panel of biologically diverse
      laboratory and clinical strains of HIV-1. The two compounds exhibited significant
      activity in all human cell lines tested, as well as in fresh human peripheral
      blood lymphocytes and macrophages. One of these two compounds (R82913) was found
      to significantly inhibit the replication of a murine retrovirus (Rauscher murine
      leukemia virus) in both UV-XC plaque formation and virus yield reduction assays.
      R86183, despite differing from R82913 only in the positioning of a single
      chlorine molecule, was not active against the murine retrovirus but was 10-fold
      more potent in inhibiting HIV-1 replication. Combination antiviral assays with
      other reverse transcriptase inhibitors, including AZT, ddC, and carbovir, yielded
      synergistic anti-HIV activity with both TIBO derivatives. Additive to slightly
      synergistic results were obtained in combinations with ddI and phosphonoformic
      acid whereas additive to antagonistic activity was detected in combination with
      dextran sulfate.

PMID- 7508724
TI  - Neonatal disease induced by SIV infection of the rhesus monkey (Macaca mulatta).
AB  - Seven 72-hr-old Indian origin rhesus monkeys (Macaca mulatta) were inoculated
      with 10 animal ID50 of SIV/DeltaB670. Nine age-matched animals were used as
      uninoculated controls. All seven inoculated animals became infected as verified
      by viral isolation and SIV p26 antigenemia. Five of seven infected animals died
      within a mean of 31 days (range, 26-41 days), with high levels of antigenemia
      beginning 1-2 weeks postinoculation (PI) that persisted until death. Absolute
      lymphocyte numbers were within normal limits in all animals in both groups
      throughout the study. Inoculated animals that died within a mean of 31 days
      (short-term survivors) had significantly lower numbers of CD4+CD29+
      (helper/inducer) lymphocytes than did long-term surviving inoculated animals
      through 3 weeks PI. Numbers of CD4+ lymphocytes were no different when controls
      were compared to all inoculated animals through 4-5 weeks PI. The two inoculated
      animals surviving 216 and 423 days PI (long-term survivors) did demonstrate
      declining CD4+ cells, but only late in disease. CD8+ lymphocytes were
      significantly lower in short-term survivors when compared to long-term survivors
      through 5 weeks PI. Antibody production against SIV viral proteins was detected
      only in the long-term survivors and was similar to results from past studies in
      juveniles. Clinical signs in the inoculated group were consistent with those seen
      in past studies on older animals. Persistent bacterial infections, primarily of
      the GI and respiratory tracts, were seen in the infected group. Aside from the
      lack of some opportunistic infections such as cytomegalovirus (CMV) and
      Pneumocystis carinii, necropsy findings were not different when compared to past
      studies on juvenile animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508725
TI  - The costs of treating febrile neutropenia in six U.K. Hospitals.
AB  - The cost of treating an episode of febrile neutropenia (FNE) in patients with
      solid tumours was estimated from the expert opinions of six consultant
      oncologists in six hospitals in England. Hospital, antibiotic, therapeutic and
      diagnostic test costs were collected. Hospitalisation, representing 62% of costs,
      was the largest single factor contributing to the mean cost per FNE of 1541
      pounds. If granulocyte colony-stimulating factor (filgrastim) can reduce the
      length of stay of such patients, then the savings will partly offset the cost of
      the drug.

PMID- 7508726
TI  - Outcome measurement in economic evaluations of growth factors.
AB  - There are several ways of measuring outcome in an economic evaluation of
      filgrastim therapy. These measures imply different types of economic evaluation.
      In all cases, the filgrastim therapy is compared with no filgrastim therapy.
      Since different therapeutic strategies are connected with uncertain consequences,
      decision trees are helpful analytical tools. The potential implications of
      different types of economic evaluations are illustrated with a simple decision
      tree.

PMID- 7508727
TI  - The impact of therapy with filgrastim (recombinant granulocyte colony-stimulating
      factor) on the health care costs associated with cancer chemotherapy.
AB  - The objective of the study was to estimate the net impact on health resource
      utilisation of using recombinant granulocyte colony-stimulating factor
      (filgrastim) following myelosuppressive chemotherapy. Cost minimisation of the
      study medication in a randomised, double-blind, placebo-controlled clinical trial
      was conducted in teaching institutions and affiliated community hospitals
      participating in a clinical trial. 68 patients with small cell lung cancer
      undergoing cyclophosphamide, doxorubicin and etoposide chemotherapy were
      randomised to blinded placebo or filgrastim study medication at three or 14
      clinical trials sites. The patients received daily subcutaneous injections of
      filgrastim or placebo, initiated 24 h after chemotherapy and continued until the
      neutrophil count exceeded 10,000 x 10(6)/l after the time of the expected nadir.
      Differences in total charges, costs and Medicare payments between treatment
      groups were the main outcomes measured. Compared to placebo patients, filgrastim
      treated patients had significantly fewer and less resource-intensive
      hospitalisations. After accounting for filgrastim purchase and administration,
      the charge model predicts overall savings from filgrastim use in a clinical
      setting in which the risk of febrile neutropenia is high for patients not
      receiving filgrastim. The Medicare and cost models predict only a partial
      recapture of the cost of filgrastim therapy. The health care resources impact of
      filgrastim was sensitive to the risk of hospitalisation with febrile neutropenia,
      and to the perspective chosen for measuring resource utilisation (charges, costs
      or Medicare payments). The adjunctive use of filgrastim following
      myelosuppressive chemotherapy leads to partial or complete recapture of the cost
      of purchasing and administering the product.

PMID- 7508728
TI  - Cytokines.

PMID- 7508729
TI  - Immunological monitoring and clinical trials of biological response modifiers.

PMID- 7508730
TI  - Bleomycins.

PMID- 7508731
TI  - Phorbol ester has different effects on forskolin and beta-adrenergic-stimulated
      cAMP accumulation in mouse parotid acini.
AB  - Phorbol 12-myristate 13-acetate (TPA) augmented the effects of forskolin, and
      inhibited the effects of isoproterenol on cAMP accumulation in mouse parotid
      acini. Treatment of intact cells with the phosphodiesterase inhibitor, 3-isobutyl
      1-methylxanthine (MIX), blocked TPA inhibition of isoproterenol but not forskolin
      stimulated cAMP accumulation. TPA also caused the translocation of protein kinase
      C (PKC) from cytosol to membrane. Pre-treatment of parotid acini with TPA for 30
      min enhanced the forskolin and isoproterenol-stimulated adenylate cyclase
      activity in isolated parotid membranes. Addition of purified PKC (pPKC) to
      parotid membranes mimicked the effects of TPA in increasing cAMP synthesis; the
      effects were blocked in the absence of calcium and phospholipid, and in the
      presence of the synthetic peptide (PKC 19-36). Purified PKC also mimicked the
      effects of TPA in augmenting forskolin and isoproterenol-stimulated adenylate
      cyclase activities in the cell-free system. Data suggest that the differential
      regulation of forskolin and isoproterenol-stimulated cAMP accumulation by TPA
      results from modification of enzymes that synthesize and degrade cAMP.

PMID- 7508732
TI  - Isobutylmethylxanthine and other classical cyclic nucleotide phosphodiesterase
      inhibitors affect cAMP-dependent protein kinase activity.
AB  - The effect of 17 inhibitors of cyclic nucleotide phosphodiesterases (PDEs) was
      assayed on cAMP binding activity of Mucor rouxii protein kinase A (PKA), on PKA
      activity in the absence of cAMP and on free catalytic subunit (C) activity.
      Isobutylmethylxanthine (IBMX), SQ 20,009 and cilostamide, at 0.2 mM, behaved as
      partial agonists of cAMP since they inhibited binding of 0.15 microM [3H]cAMP to
      the regulatory subunit (R), stimulated slightly PKA activity in the absence of
      cAMP and did not modify C activity. Amrinone at 0.2 mM inhibited C activity
      competitively towards ATP. These four compounds displayed the same effects when
      assayed on eukaryotic protein kinase A types I (PKI) and II (PKII). The combined
      effect of IBMX and cAMP was analysed on Mucor PKA. Under dissociating conditions
      (+ 0.5 M NaCl) IBMX antagonized activation by low concentrations of cAMP, while
      in the absence of NaCl, IBMX potentiated the stimulating activity of cAMP.

PMID- 7508733
TI  - Platelet-activating factor activates a Ca(2+)-dependent K+ channel which is not
      involved in c-fos expression in human B lymphoblastoid cells.
AB  - In this report, it is shown that the platelet-activating factor (PAF) induced, in
      human B lymphoblastoid cells, 86Rb+ influx and efflux suggesting that it
      activated a K+ channel. Opening of this channel was dependent on PAF-induced Ca2+
      mobilization. Ionomycin and thapsigargin--a specific inhibitor of (Ca(2+)-Mg2+)
      ATPase--mimicked the effect of PAF both on intracellular calcium and activation
      of the channel. This channel was inhibited by charybdotoxin, high doses of
      tetraethylammonium and barium but was insensitive to apamin, 4-aminopyridine.
      These features indicate that PAF activated a Ca(2+)-dependent K+ channel. In
      these cells, PAF also induced the expression of c-fos oncogene. This effect was
      not affected by charybdotoxin indicating that this channel is not involved in the
      control of early gene transcription.

PMID- 7508734
TI  - Two types of prostacyclin receptor coupling to stimulation of adenylate cyclase
      and phosphatidylinositol hydrolysis in a cultured mast cell line, BNu-2cl3 cells.
AB  - Prostacyclin (PGI2)-mediated signal transduction was examined in interleukin 3
      (IL-3)-dependent BNu-2cl3 mast cells. Iloprost, a stable PGI2 analogue, induced
      the accumulation of intracellular cAMP and IP3, and an increase in the
      intracellular Ca2+ concentration. Pretreatment of the cells with a protein kinase
      C activator, 12-O-tetradecanoyl phorbol 13-acetate, suppressed the iloprost
      induced IP3 accumulation and Ca2+ mobilization, but inversely potentiated the
      cAMP accumulation, suggesting that neither of these signal transduction pathways
      of iloprosts is the result of a secondary effect of activation of the other.
      Removal of IL-3 from the culture medium reduced the iloprost-induced IP3
      accumulation and Ca2+ mobilization, while it had no effect on the iloprost
      induced cAMP accumulation at all. These results taken together suggest that BNu
      2cl3 cells express two types of PGI2 receptor; one couples to stimulation of
      adenylate cyclase, its expression being independent of IL-3, while the other
      couples to phosphatidylinositol hydrolysis, its expression being dependent on IL
      3.

PMID- 7508735
TI  - Use of inexpensive O antisera as the detecting antibodies for Salmonella antigens
      in the polymyxin-cloth enzyme immunoassay.
AB  - The application of O antigen-specific antisera to the detection of Salmonella
      lipopolysaccharide (LPS) antigens was examined in an enzyme immunoassay using
      polymyxin-coated polyester cloth. The LPS antigens were extracted with
      deoxycholate and captured on polymyxin-cloth. A mixture of rabbit antisera to
      Salmonella O antigens was allowed to react with the captured antigens, and the
      reacted antibodies were detected by an anti-rabbit IgG-peroxidase conjugate. The
      assay gave positive results with 40 different Salmonella serotypes which
      represented more than 99.9% of the serogroups isolated from over 122,000 food,
      feed and environmental samples analysed at Laboratory Services Division,
      Agriculture Canada, from 1975 to 1990. Strong cross-reactivity with
      Staphylococcus aureus was eliminated by pregrowth of the organisms in the
      presence of sodium deoxycholate. The O antisera were commercially available and
      are more economical than monoclonal or affinity purified polyclonal antibodies.

PMID- 7508736
TI  - Treatment of bacterial, fungal, and parasitic infections in the HIV-infected
      host.
AB  - In the human immunodeficiency virus (HIV) infected patient, skin infections
      caused by S aureus are extremely common. Impetigo, ecthyma, and folliculitis are
      all seen. Recurrences are common due to a nasal carriage rate of 50%.
      Dermatophytosis usually manifests as tinea pedis or unguium and is caused by
      Trichophyton rubrum. Oral candidiasis may be the initial evidence of HIV
      infection, and is predictive of more rapid progression to acquired immune
      deficiency syndrome (AIDS). Topical agents are usually effective for oral
      lesions, but involvement of the esophagus requires oral imidazole therapy.
      Systemic fungal infections are most commonly caused by cryptococcosis or
      histoplasmosis. The finding of either of these infectious agents in the skin is
      pathognomonic of disseminated infection. Cryptococcus presents as umbilicated
      papules resembling molluscum or as large ulcerations. Histoplasmosis has no
      specific cutaneous morphology. Scabies is very common in HIV-infected persons,
      and once the helper T-cell count is less than 200, it may present atypically.
      Permethrin is the recommended treatment in this setting.

PMID- 7508737
TI  - Thyroid autoantibodies in the subsets of lupus erythematosus: correlation with
      other autoantibodies and thyroid function.
AB  - Thirty four sera from: 12 patients with Systemic Lupus Erythematosus (SLE), 9
      with Subacute Cutaneous Lupus Erythematosus (SCLE) and 13 with Discoid Lupus
      Erythematosus (DLE) (disseminatus 3, localised 10) were tested for the presence
      of: (a) anti-thyroglobulin and anti-microsomal autoantibodies (b) anti-Sm/RNP,
      anti-doublestranded. DNA (anti-ds. DNA), anti-single-Stranded. DNA (anti-ss.
      DNA), anti-cardiolipin (anti-Cl), anti-SSA, anti-SSB, Antinuclear Antibodies
      (ANA). T3, T4, TSH levels were also determined. Five patients with SLE (41.6%), 4
      with SCLE (44.4%), and 2 with DLE (15.3%) had thyroid autoantibodies and only
      three of the 41 controls (7.3%). Five patients (14.7%), especially from SLE and
      SCLE groups, had biochemical hypothyroidism whereas only one had hyperthyroidism.
      Statistical evaluation for the possible coexistence of thyroid autoantibodies
      with a panel of lupus characteristic autoantibodies, revealed highly significant
      correlations with anti-Sm/RNP, IgG (p = 0.003) and anti-ds. DNA, IgM (p = 0.012).
      It may be concluded, that not only SLE but also SCLE predisposes to autoimmune
      thyroid disease and the prevalence of the latter is related to a great extent to
      the subset of the LE spectrum. From these results and from the inhibition
      experiments, it seems that some of the specific mono- or polyclonal
      autoantibodies may be multiple organ reactive.

PMID- 7508738
TI  - Thyroid function parameters and TSH-receptor antibodies in healthy subjects and
      Graves' disease patients: a sequential study before, during and after pregnancy.
AB  - The changes in thyroid function and in TSH receptor antibody titers were analyzed
      in a prospective sequential study before, during and after pregnancy in a group
      of 15 healthy women and 45 patients with Graves' disease. Twenty-five patients
      with Graves' disease were untreated before pregnancy (Group A) and twenty treated
      with carbimazole throughout pregnancy (Group B). In healthy pregnant women serum
      FT4 levels were slightly but significantly elevated early in pregnancy (p < 0.05)
      and lower during the third trimester (p < 0.01), compared to pregestational
      values (although within the reference range of nonpregnant subjects). During
      postpartum, serum FT4 reverted to values similar to those found before pregnancy.
      Serum TSH levels showed a slight increment during gestation with a significant
      decrease (p < 0.01) in the early postpartum period. There was a significant
      increase in serum thyroglobulin (Tg) during the first trimester (p < 0.01); Tg
      levels remaining markedly elevated throughout gestation. After delivery, Tg
      progressively decreased, but were still above normal, six months later in 27% of
      subjects. TSH-receptor antibody titers were normal but tended to decrease during
      late gestation; a significant rebound was observed in late postpartum, even
      though most individual values remained in the normal range. When we compared
      "active" and "remission" Graves' disease patients, the concentration of FT4 was
      significantly higher in group B ("active") than in group A ("remission" (p <
      0.01) during early gestation. Serum Tg was also significantly higher in Group B
      than in Group A before pregnancy (p < 0.01), and during late gestation and
      postpartum (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508739
TI  - Serum selenium concentrations in patients with autoimmune thyroiditis and non
      toxic nodular goiter.
AB  - Selenium (Se) deficiency is said to contribute to the atrophy of the thyroid
      gland in certain endemic goiter areas in Africa. To test the hypothesis that, a
      low Se intake could protect against goiter development in autoimmune thyroiditis,
      we analysed the Se concentration in 20 patients with the atrophic variant of
      lymphocytic thyroiditis, 23 patients with Hashimoto's thyroiditis and 23 patients
      with non-toxic nodular (colloid) goiter. Twenty healthy females served as
      controls. We did not find any significant difference in serum selenium (S-Se)
      levels between the patients with the various thyroid disorders or between
      patients and controls. There was no difference in the S-Se concentration and the
      triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) or thyroglobulin
      concentrations in serum. Thus, the Se status had no impact on the development of
      goiter.

PMID- 7508740
TI  - Psychological changes during thyrotoxicosis.
AB  - Psychological changes during hyperthyroidism are well known. However, no studies
      were performed in order to quantify or evaluate them in numerical details. We
      have studied the personality of 15 women with Graves' disease by means of the
      16PF Cattell Test, before and after treatment of hyperthyroidism with surgery or
      radioactive iodine. The first test was performed when patients relapsed the
      thyrotoxicosis after a period of euthyroidism, achieved through the treatment
      with antithyroid drugs during one year. At the time of the second test all
      patients had 6-12 months of euthyroidism. Hormonal circulating levels were as
      follow (mean +/- SEM): a) at the first test, T3 = 320 +/- 27 ng/dl, T4 = 19.7 +/-
      1.2 micrograms/dl, TSH < 0.2 microU/ml; b) at the second test, T3 = 128 +/- 9
      ng/dl, T4 = 8.8 +/- 0.8 micrograms/dl, TSH = 1.9 +/- 0.4 microU/ml. Differences
      between both tests were expressed for each factor as the mean difference +/- SEM
      (paired "t" test). After treatment patients were: 1) more relaxed and emotionally
      trustful and cooperative (factor A + 1.06 +/- 0.39, p < 0.02); 2) better and
      faster intellectual comprehension (factor B + 0.80 +/- 0.31, p < 0.05); 3) more
      capable of analysis (factor Q1 + 0.93 +/- 0.41, p < 0.05); 4) lower in lingering
      anxiety and tension (factor Q4-0.87 +/- 0.36, p < 0.05); 5) more independent,
      less submissive (factor QIV + 0.88 +/- 0.41, p < 0.05); 6) more relaxed (factor
      QI-0.69 +/- 0.20, p < 0.01). The other factors remained unchanged.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7508741
TI  - The usefulness of computer-aided karyometric examination in preoperative
      differentiation of follicular neoplasms of the thyroid gland.
AB  - Fine-needle aspiration biopsy (FNAB) is the most important procedure in
      preoperative diagnosis of thyroid neoplasms. However, routine cytological
      examination is insufficient for differentiation between follicular adenoma and
      follicular carcinoma. Therefore, we decided to assess the usefulness of
      karyometric analysis in the examination of aspirates from these neoplasms.
      Morphometric analysis was performed with the use of the computer system for
      karyometric measurements--"Karyometry Manager" ver. 1.2. We examined cytological
      smears derived from 26 patients. In 10 of them a nodular goitre was diagnosed in
      both cytological and histopathological examinations. In the other 16 patients,
      "follicular neoplasms" were found in cytological examination. These proved to be
      follicular adenomas (8 cases) and follicular carcinomas (8 cases) on
      histopathological examination. The following morphometric parameters were
      measured in 100 nuclei per smear: volume, intersection area, perimeter, convexity
      coefficient and shape coefficient. We found that: 1) the mean volume and the mean
      intersection area of thyrocyte nuclei from follicular carcinomas were
      significantly (p < 0.001) greater than those of nuclei from adenomas or nodular
      goitres; 2) the mean perimeter of thyrocyte nuclei from follicular carcinomas was
      significantly greater than the mean perimeter of thyrocyte nuclei from follicular
      adenomas (p < 0.025) and nodular goitres (p < 0.001); 3) the mean nuclear area of
      thyrocytes from follicular adenomas was significantly greater than that of
      thyrocytes from nodular goitres (p < 0.05). Our results show that karyometric
      analysis can be useful in cytological differentiation of follicular neoplasms.

PMID- 7508742
TI  - Comparison of the effect of a single oral L-thyroxine dose (150 micrograms) in
      tablet and in solution on serum thyroxine and TSH concentrations.
AB  - 150 micrograms of L-thyroxine were administered to each of 14 euthyroid goitrous
      patients orally between 7:30 and 8:30 a.m. after fasting overnight. The L-T4 dose
      given was one and half tablets of the drug "Eutirox" (L-T4 tablet of 100
      micrograms distributed by Bracco, Milan, Italy) or one and half ml of the
      solution "Tiroxen" (solution containing 100 micrograms/ml of L-T4 distributed by
      Laboratori Baldacci, Pisa, Italy). Two studies (one with tablet and one with
      solution) were performed on each patient. The tablet or the liquid form of L-T4
      were administered in random order. In each study a blood sample for serum hormone
      determination was drawn immediately before L-T4 administration, then 30 minutes
      later and every hour up to the fifth hour after. The second study was performed
      in similar fashion later. The mean serum TT4 concentration value at any time was
      very similar in the two studies, thus showing the same time course after the
      administration of solution and the tablet formulation. The mean basal TT4 value
      (9.07 +/- 0.56 and 8.90 +/- 0.73 micrograms/dl respectively) increased
      significantly at the first and second hours. The highest value was reached at the
      second and at the third hour after the solution (11.15 +/- 0.58 micrograms/dl)
      and the tablet (11.81 +/- 0.78 micrograms/dl) respectively. Subsequently, the
      mean TT4 values remained significantly higher than basally over the entire 5
      hours. The FT4 mean serum concentration at all times were very similar in the two
      studies and showed the same time course.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508743
TI  - Clonal analysis of the atopic immune response to the group 2 allergen of
      Dermatophagoides spp.: identification of HLA-DR and -DQ restricted T cell
      epitopes.
AB  - The group 2 allergens of Dermatophagoides spp. (house dust mite, HDM) are a major
      immunological target for IgE antibodies in the allergic immune response of HDM
      atopic individuals. In this report the heterogeneity of the T cell repertoire
      reactive with the group 2 allergen of Dermatophagoides pteronyssinus (Der p 2) of
      a HDM allergic individual was investigated using overlapping synthetic peptides.
      By clonal analysis four distinct T cell epitopes were identified, located within
      residues 16-31, 22-40, 82-100, and 111-129. The importance of these epitopes was
      confirmed by investigation of the peripheral T cell repertoire, with the
      polyclonal T cell response to Der p 2 failing to show marked variations in
      epitope specificity over time. Serological inhibition studies and the use of
      Epstein-Barr virus transformed B cell lines characterized for their expression of
      HLA-D region gene products demonstrated that recognition of peptides 16-31 and
      111-129 was restricted by HLA-DQ (DQB1*0301), whereas peptide 82-100 is
      recognized in association with HLA-DR (DRB1*1101). Peptide 22-40 was presented by
      both HLA-DRB1*1101 and -DQB1*0301 class II molecules. The potential application
      of these findings lies in the design of peptide-based immunotherapeutics for the
      management of HDM allergic disease.

PMID- 7508744
TI  - Protein synthesis in splanchnic tissues of sheep offered two levels of intake.
AB  - Protein synthesis rates were measured in liver and gastrointestinal tract (GIT)
      sections of fattening sheep offered lucerne (Medicago sativa) pellets at either
      1.25 or 2 times energy maintenance. The measurement technique involved a large
      dose of [1-13C]valine over 60 min. Animals on the higher intake had a larger mass
      of liver protein (143 v. 100 g, P = 0.02), similar fractional synthesis rates
      (ks; 22.5 v. 22.1%/d, not significant) and greater absolute amounts of protein
      synthesis (32 v. 23 g/d; P = 0.016) compared with those on the smaller amount of
      ration. The ks values and RNA: protein in the GIT sections also tended to
      increase with food intake. Estimated total GIT protein synthesis was
      approximately three-fold that in liver and probably constituted 25-35% of whole
      body synthesis. All splanchnic tissues measured had lower translational
      efficiencies (g protein synthesized/d per g total RNA) than reported for milk-fed
      and newly-weaned lambs and this may relate to the decline in the rate of protein
      deposition as lambs progress to the fattening condition.

PMID- 7508745
TI  - CD62/P-selectin binding sites for myeloid cells and sulfatides are overlapping.
AB  - P-Selectin (CD62/GMP140/PADGEM) is an inducible cell-surface glycoprotein
      expressed by endothelial cells and platelets following stimulation by
      inflammatory mediators such as thrombin, histamine, or peroxides. P-Selectin
      mediates the binding of leukocytes to activated vascular endothelium at sites of
      inflammation and plays a role in mediating the binding of activated platelets to
      leukocytes and the vascular cell wall. The adhesive function of P-selectin is
      mediated by its calcium-dependent (or C-type) lectin domain, which is known to
      bind to carbohydrate ligands including fucosyl-N-acetyllactosamine (Lex, CD15),
      sialyl-Lex, and 3-sulfated galactosylceramides (sulfatides). Sulfatides can
      efficiently block P-selectin/myeloid cell binding in vitro and are excreted at
      high levels by activated granulocytes. These observations led to the hypothesis
      that sulfatide may play a role in facilitating the disengagement of CD62,
      allowing the efficient exit of granulocytes from the blood stream at sites of
      inflammation. In this report, we extend our previous mutagenesis analysis of the
      P-selectin binding site [Hollenbaugh, D., Bajorath, J., Stenkamp, R., & Aruffo,
      A. (1993) Biochemistry 32, 2960] and show that replacement of Tyr48 with Ser or
      Lys113 with Arg results in P-selectin mutants that, although correctly folded, do
      not bind to HL60 cells. These results suggest that the conservation of charged
      and hydrogen-bonding site chains is not sufficient to maintain the P-selectin
      function and that the exact stereochemistry provided by the side chains of
      residues lining the P-selectin binding pocket is critical for P-selectin
      binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508746
TI  - Catalytically distinct conformations of the ribonuclease H of HIV-1 reverse
      transcriptase by substrate cleavage patterns and inhibition by azidothymidylate
      and N-ethylmaleimide.
AB  - The RNase H activity of recombinant HIV-1 reverse transcriptase (RT) has been
      characterized with respect to inhibition by azidothymidylate (AZTMP) and N
      ethylmaleimide (NEM) and to cleavage patterns using either poly(rA)/poly(dT) or
      poly(rG)/poly(dC) as model substrate and either Mg2+ or Mn2+ as divalent cation
      activator. The inhibitory potency of AZTMP and other nucleotide analogues was
      found to be dependent on both the composition of the substrate and the divalent
      cation. The enzyme was significantly more sensitive to AZTMP inhibition with
      poly(rG)/poly(dC) than with poly(rA)/poly(dT) as substrate and in Mn2+ than in
      Mg2+ with either substrate. Kinetic studies indicated that AZTMP is a competitive
      inhibitor with respect to the substrate in Mn2+ whereas it behaves as an
      uncompetitive inhibitor in Mg2+. These results suggest that the enzyme may exist
      in two distinct forms depending on whether Mg2+ or Mn2+ is the divalent cation
      activator. Consistent with this suggestion is the alteration in the mode of
      cleavage of the substrate upon substitution of Mg2+ with Mn2+. In Mg2+,
      hydrolysis of poly(rA)/poly(dT) appears to be solely endonucleolytic, whereas in
      Mn2+, hydrolysis is both endonucleolytic and exonucleolytic. With
      poly(rG)/poly(dC) as substrate, hydrolysis is both endonucleolytic and
      exonucleolytic in either Mg2+ or Mn2+. There is a positive correlation between
      sensitivity to AZTMP and production of mononucleotides, suggesting that the
      exonuclease activity of RNase H is preferentially inhibited by AZTMP. The
      sensitivity of RNase H to inhibition by N-ethylmaleimide was also found to be
      markedly influenced by the substrate composition and the divalent cation
      activator, being most sensitive under conditions in which endonucleolytic
      activity predominates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508747
TI  - Synergistic activation of tyrosine phosphorylation by o-vanadate plus calcium
      ionophore A23187 or aromatic 1,2-diols.
AB  - We have shown previously that treatment of WB rat liver epithelial cells with the
      Ca2+ ionophore A23187 provokes a rapid increase in protein-tyrosine
      phosphorylation that faithfully reproduces the Ca(2+)-dependent response seen
      with angiotensin II. In the presence of the tyrosine phosphatase inhibitor o
      vanadate (2.0-200 microM), the tyrosine phosphorylation response to A23187 was
      increased > 10-fold in magnitude. This synergistic effect of A23187 and vanadate
      is clearly distinct from the combined effect of angiotensin II and vanadate,
      which was merely additive. Chelation of either extracellular or intracellular
      Ca2+ abolished the synergistic response to ionophore and vanadate, indicating its
      Ca2+ dependence. That divergent pathways were involved in the angiotensin II and
      the A23187/vanadate responses was shown definitely by studies of GN4 cells, a
      transformed line derived from WB cells by carcinogen treatment. GN4 cells are 2-3
      fold more responsive than WB cells to angiotensin II-dependent tyrosine kinase
      activation, yet they completely lacked the synergistic tyrosine phosphorylation
      response to A23187/vanadate. To test the role of arachidonic acid metabolites in
      the A23187/vanadate response, cells were pretreated with either indomethacin or
      nordihydroguaiaretic acid (NDGA). Neither compound was inhibitory, but
      surprisingly, NDGA plus vanadate closely mimicked the A23187/vanadate response in
      WB cells and, like A23187/vanadate, was ineffective in GN4 cells. NDGA contains
      catechol nuclei (i.e., aromatic 1,2-diols) and therein resembles the flavonoid
      anti-oxidant quercetin, another compound found to increase tyrosine
      phosphorylation synergistically with vanadate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508748
TI  - Amino acid sequence of human pregnancy-associated plasma protein-A derived from
      cloned cDNA.
AB  - The amino acid sequence of human pregnancy-associated plasma protein-A (PAPP-A),
      a component of the circulating complex with the proform of eosinophil major basic
      protein (proMBP), has been determined from partial protein sequencing and from
      sequencing of cloned cDNA. The PAPP-A monomer contains 1547 amino acid residues,
      but is derived from a larger precursor of placental origin. PAPP-A contains 82
      Cys residues, which are all bridged, 14 putative sites for N-glycosylation, and 7
      putative sites for attachment of glycosaminoglycan groups. The C-terminal part of
      PAPP-A contains 5 approximately 60-residue motifs related to the short consensus
      repeats of complement proteins and selectins. The SCRs presently known can be
      grouped into three classes: complement-type, class I; selectin-type, class II;
      PAPP-A-type, class III. PAPP-A further contains three approximately 26-residue
      motifs, related to the lin-notch motifs of proteins regulating early tissue
      differentiation, and, in addition, a putative Zn2+ binding site similar to that
      found in many metalloproteinases has been identified. Apart from these features,
      the PAPP-A sequence is not related to other known protein sequences.

PMID- 7508749
TI  - Expression of major histocompatibility antigens and vascular adhesion molecules
      on human cardiac allografts preserved in University of Wisconsin solution.
AB  - The impact of cold storage of cardiac allografts on expression of major
      histocompatibility complex antigens and vascular adhesion molecules is not known.
      We obtained serial endomyocardial biopsy specimens at harvest, on implantation,
      and approximately 15 minutes after reperfusion from six consecutive human cardiac
      allografts stored in University of Wisconsin solution. Cold ischemia time was 187
      +/- 45 minutes. A fourth endomyocardial biopsy specimen was obtained from the
      recipients of cardiac allografts 1 week after operation. Expression of major
      histocompatibility complex antigens and vascular adhesion molecules was studied
      by immunohistochemistry. The intensity was scored blindly by a semiquantitative
      method. On vascular endothelial cells, the expression of major histocompatibility
      complex class I and II antigens was strong; ICAM-1 expression was moderate, and
      expression of VCAM-1 and ELAM-1 was weak to absent. The expression of these
      antigens on vascular endothelial cells did not change in sequential biopsy
      specimens. The expression of major histocompatibility complex class I antigens on
      myocardial cells was weak and remained unchanged. Myocardial cells did not
      express major histocompatibility complex class II antigens, ICAM-1, VCAM-1, or
      ELAM-1 on serial examinations. During cold storage of cardiac allografts in
      University of Wisconsin solution, the expression of major histocompatibility
      complex antigens and vascular adhesion molecules on endothelial cells and
      myocardial cells remains unchanged.

PMID- 7508750
TI  - Combined therapy with FK-506 and cyclosporine for canine lung
      allotransplantation: immunosuppressive effects and blood trough levels.
AB  - The therapeutic and adverse effects of FK-506 and cyclosporine used in
      combination were examined in 35 adult mongrel dogs with allotransplantation of
      the left lung. The experimental animals were allocated to six groups: group A,
      optimal dose of FK-506 (n = 5, FK-506 0.1 mg/kg/day, intramuscularly); group B,
      optimal dose of cyclosporine, (n = 5, cyclosporine 20 mg/kg/day, by mouth); group
      C (n = 5, FK-506 0.03 mg/kg/day, intramuscularly); group D (n = 5, cyclosporine 6
      mg/kg/day, by mouth); group E (n = 5, FK-506 0.03 mg/kg/day+cyclosporine 6
      mg/kg/day); and group F (n = 10, FK-506 0.05 mg/kg/day+cyclosporine 10
      mg/kg/day). The animals were killed on postoperative day 28 or when extreme
      deterioration had developed. In groups C and D, the grafts underwent moderate to
      severe rejection. The treatment in group E resulted in insufficient
      immunosuppression, although additional effect was noted. The rejection was
      suppressed at least as strongly in group F as in groups A and B. One death
      occurred in each of groups A and F from hematemesis. The blood concentrations of
      FK-506 and cyclosporine in group E were not higher than in groups C and D. The
      whole blood concentrations of FK-506 deviated less, and they were superior to the
      serum concentrations as a monitor. The combination of FK-506 and cyclosporine at
      one half of their optimal doses suppressed the rejection almost completely and
      did not increase the adverse effects.

PMID- 7508751
TI  - Heart transplantation in children who have undergone previous heart surgery: is
      it safe?
AB  - As heart transplantation becomes more commonly applied to the pediatric
      population, it is important to determine if previous palliative or reparative
      operations increase the risk of transplantation. Since 1988, 13 children aged 23
      months to 14 years (mean 9.5 years) who had undergone previous heart operations
      underwent orthotopic heart transplantation. These children had undergone an
      average of 3.2 previous operations (range 1 to 7):1.9 sternotomies (range 0 to 5)
      and 1.2 thoracotomies (range 0 to 3). Three children had undergone only
      palliative operations (Norwood procedure, Waterston shunt, and transthoracic
      pacemaker); the remaining 10 had undergone at least one "corrective" operation:
      four valve replacements or repairs (three mitral and one aortic), three Fontan
      procedures, one Rastelli procedure, one double-outlet right ventricle repair, and
      one ventricular septal defect repair. At the time of transplantation, seven
      patients (54%) were on inotropic support, two with mechanical ventilation. Three
      patients (23%) had significant levels of preformed antibodies necessitating a
      prospective cross-match, which significantly delayed transplantation. The
      transplant procedure was complicated by the need for pulmonary arterial
      reconstruction in six patients (46%), transposition of the great arteries in
      three patients (23%), and atrial baffling to redirect anomalous venous drainage
      in one patient (8%). There was one death 4 days after surgery from sepsis in a
      patient who had undergone a previous Konno procedure who required 24 hours of
      mechanical right ventricular assistance after transplantation. Two children (15%)
      required mediastinal exploration for bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508753
TI  - Ca2+ entry through L-type voltage-sensitive Ca2+ channels stimulates the release
      of human chorionic gonadotrophin and placental lactogen by placental explants.
AB  - The release of human chorionic gonadotrophin (hCG) and placental lactogen (hPL)
      by human placental explants can be stimulated by Ca2+ entry. The aim of the
      present study was to characterize the modality of Ca2+ entry in the presence of
      high extracellular K+ concentration ([K+]o). A rise in [K+]o from 5 to > or = 50
      mM induced a rapid and marked increase in the release of hCG and hPL from human
      term placental explants. The stimulatory effects of an excess [K+]o on the
      release of hCG and hPL were blocked in the absence of extracellular Ca2+ or in
      the presence of 0.5 mM Co2+. The presence of 50 microM methoxyverapamil, 20
      microM nifedipine or 40 microM Cd2+ in the medium inhibited the stimulatory
      effects of [K+]o addition. Lastly, 40 microM Ni2+ failed to affect the increases
      in hCG and hPL releases elicited by [K+]o addition. Our data clearly show that a
      rise in [K+]o stimulates the release of hCG and hPL from placental explants.
      These secretory effects can be viewed as resulting from a Ca2+ entry through
      voltage-sensitive Ca2+ channels of the L-type.

PMID- 7508752
TI  - New small molecule immunosuppressants for transplantation: review of essential
      concepts.
AB  - More immunosuppressive drugs than ever have recently graduated from the
      laboratory to extensive clinical trials of their safety and efficacy in patients
      undergoing transplantation. Although none of these drugs is perfect, they control
      different forms of rejection in stringent animal models more effectively than
      other immunosuppressants; yet these novel molecules suppress the immune system
      far more specifically than steroids and regimens that cause lymphopenia.
      Cyclosporin G and IMM 125 (analogues of cyclosporine) and FK506 are the only
      drugs that selectively inhibit T-cell proliferation by blocking cytokine
      synthesis. The primary action of rapamycin and leflunomide appears to be an
      inhibition of the actions of cytokines and growth factors on T, B, and some
      nonimmune cells. T and B cells are more sensitive than nonimmune cells to the
      depletion of purines and pyrimidines caused by mizoribine, mycophenolic acid, and
      brequinar sodium. Nucleotide depletion causes interruption of DNA synthesis and
      glycosylation of adhesion molecules in immune cells. Further differentiation of T
      and B cells after proliferation into fully functional immune cells is inhibited
      by unknown mechanisms by brequinar and deoxyspergualin. On the basis of
      preclinical studies, these drugs may effectively suppress clinical rejection that
      is (1) acute (all drugs), (2) chronic (rapamycin, leflunomide, and mycophenolic
      acid), or (3) antibody-mediated (brequinar, deoxyspergualin, mycophenolic acid,
      and rapamycin). Some drugs (FK506, deoxyspergualin, mycophenolic acid, rapamycin,
      and leflunomide) may reverse acute rejection refractory to conventional
      immunosuppression. These new drugs not only block different biochemical steps
      that normally lead to fully functional T and B cells after stimulation by
      alloantigen, but their toxicity profiles also differ. Results from preclinical
      studies predict that use of selected combinations of these drugs in patients will
      be more effective, less nephrotoxic, less myelotoxic, and less broadly
      immunosuppressive than current regimens based on cyclosporine, T-cell depletion,
      steroids, and azathioprine ... at least, that's the idea! Or as former Vice
      President Dan Quayle said, "It's a question of whether we're going to go forward
      into the future, or past to the back."

PMID- 7508754
TI  - Effect of inhibition of microsomal Ca(2+)-ATPase on cytoplasmic calcium and
      enzyme secretion in pancreatic acini.
AB  - We used thapsigargin (TG), 2,5-di-tert-butyl-1,4-benzohydroquinone (BHQ) and
      cyclopiazonic acid (CPA), each of which inhibits microsomal Ca(2+)-ATPase, to
      evaluate the effects of this inhibition on cytoplasmic free calcium ([Ca2+]i) and
      secretagogue-stimulated enzyme secretion in rat pancreatic acini. Using single
      cell microspectrofluorimetry of fura-2-loaded acini we found that all three
      agents caused a sustained increase in [Ca2+]i by mobilizing calcium from inositol
      (1,4,5)-trisphosphate-sensitive intracellular calcium stores and by promoting
      influx of extracellular calcium. Concentrations of all three agents that
      increased [Ca2+]i potentiated the stimulation of enzyme secretion caused by
      secretagogues that activate adenylate cyclase but inhibited the stimulation of
      enzyme secretion caused by secretagogues that activate phospholipase C. With BHQ,
      potentiation of adenylate cyclase-mediated enzyme secretion occurred immediately
      whereas inhibition of phospholipase C-mediated enzyme secretion occurred only
      after several min of incubation. In addition, the effects of BHQ and CPA on both
      [Ca2+]i and secretagogue-stimulated enzyme secretion were reversed completely by
      washing whereas the actions of TG could not be reversed by washing.
      Concentrations of BHQ in excess of those that caused maximal changes in [Ca2+]i
      inhibited all modes of stimulated enzyme secretion by a mechanism that was
      apparently unrelated to changes in [Ca2+]i. Finally, in contrast to the findings
      with TG and BHQ, CPA inhibited bombesin-stimulated enzyme secretion over a range
      of concentrations that was at least 10-fold lower than the range of
      concentrations over which CPA potentiated VIP-stimulated enzyme secretion.

PMID- 7508755
TI  - Tissue protein turnover in animals treated with the mixed beta-agonist
      metaproterenol: influence of dose, route and pattern of administration.
AB  - beta-Adrenergic agonists have been shown to increase protein deposition as a
      result of changes in the balance between protein synthesis and degradation rates.
      The aim of this study is to investigate the effect of the treatment with the non
      selective beta-adrenergic agonist, metaproterenol, on protein metabolism in rats
      as well as the influence of the route and pattern of administration. A short- and
      long-term experimental trial were carried out. After the short-term treatment
      with the beta-agonist (1 mg/kg), neither protein nor nucleic acids were affected
      in liver or gastrocnemious muscle, while cathepsin A activity, an index of
      protein degradation, significantly increased in muscle. However, cathepsin A
      activity was reduced in muscle by the oral administration during 21 days of
      metaproterenol (2 ppm/day), but not by the subcutaneous injections (0.1
      mg/kg/day). On the other hand, RNA/DNA, an index of protein synthesis capacity,
      and protein/DNA, an indicator of cell size, significantly diminished in muscle
      after the subcutaneous long-term treatment but did not change in the liver of
      treated rats. Our study has demonstrated a different outcome of a mixed beta
      adrenergic agonist on protein metabolism depending on the duration of the
      treatment and the route of administration.

PMID- 7508757
TI  - Effects of growth hormone and gonadotropin on the insulin-like growth factor
      system in the porcine ovary.
AB  - The effects of growth hormone (GH) +/- pregnant mare's serum gonadotropin (PMSG)
      on levels of insulin-like growth factor (IGF)-I and -II and IGF binding protein
      (BP)-2 and -3 in serum and follicular fluid (FFI) and on the expression of their
      mRNA in the ovaries of prepubertal gilts were determined. Steroids in FFI were
      also quantified. In the first experiment, GH, given for either 20 or 40 days,
      caused a distinct (threefold, p < 0.05) increase in IGF-I in both serum and FFI
      with no change in the FFI:serum ratio (0.65). Effects of GH on IGF-II were
      opposite, with a drop in circulating and FFI levels (p < 0.05). In contrast to
      data for IGF-I, FFI levels were higher than those in serum for IGF-II (1.42,
      FFI:serum); IGF-II levels and the ratio fell after GH treatment. GH for either 20
      days or 40 days increased serum IGBP-3 to 140% and 250% of control values while
      decreasing serum IGFBP-2 by 46% and 31%, respectively (p < 0.001). FFI IGFBP-3
      was increased to a similar extent by GH (p < 0.005), but IGFBP-2 was not
      affected. Neither progesterone (P4) nor estradiol (E2) was affected by treatment
      with GH. However, androstenedione (A4) was decreased by 20-day and 40-day GH
      treatment relative to the respective controls (p < 0.05). In the second
      experiment, PMSG resulted in a modest (28%) increase in intrafollicular IGF-I (p
      < 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508756
TI  - Retinoids regulate gonadotropin action in cultured rat Sertoli cells.
AB  - The effect of retinoids on cultured rat Sertoli cells was studied by evaluation
      of cAMP and estradiol production after gonadotropin stimulation in the presence
      or absence of the retinoid. Sertoli cells cultured in the presence of FSH produce
      a high amount of cAMP and increase their aromatase activity. The addition of
      retinol alone has no effect on cAMP and estradiol production; however, the
      presence of retinol in the culture medium exerts an inhibitory effect on Sertoli
      cell response to FSH stimulation. In particular, FSH-induced cAMP production of
      rat Sertoli cells was significantly reduced (50-60% decrease) both by retinol and
      by retinoic acid. This effect was observable during the first ten days of culture
      and was also evident when Sertoli cells were cultured in the presence of retinol
      and methylisobutylxanthine, an inhibitor of phosphodiesterase activity. Cholera
      toxin-stimulated cAMP levels were reduced by retinol, whereas forskolin-induced
      elevation of cAMP levels was not affected by vitamin treatment. The inhibitory
      effect of retinoids on FSH-stimulated aromatase activity of Sertoli cells, which
      is cAMP mediated, was also evident. In conclusion, the present study demonstrates
      that retinoids modulate FSH action on cultured rat Sertoli cells and decrease
      cAMP production.

PMID- 7508758
TI  - Porcine stem cell factor/c-kit ligand: its molecular cloning and localization
      within the uterus.
AB  - Stem cell factor (SCF), or c-kit ligand, is a multipotent growth factor that has
      been implicated in an important role in various aspects of animal development,
      including maintenance of the viability of primordial germ cells. A porcine SCF
      (pSCF) cDNA was generated from porcine uterine endometrial mRNA by reverse
      transcriptase-polymerase chain reaction (RT-PCR), and its nucleotide sequence was
      determined. The 952-bp pSCF cDNA contained an open reading frame encoding 274
      amino acids. The deduced amino acid sequence of pSCF is approximately 86%, 83%,
      and 82%, identical to human, rat, and mouse SCFs, respectively; and it contains
      the four conserved cysteine residues and Asn-linked glycosylation sites. One
      additional amino acid was identified in pSCF, Glu130, which is not in the human
      (hSCF), rat (rSCF), or mouse (mSCF) sequences. Northern analysis of poly(A)+ RNA
      obtained from Day 16 pregnant endometrium revealed a transcript of approximately
      6.5 kb. The size of this transcript is consistent with the size of full-length
      SCF mRNA, and the occurrence of alternatively spliced pSCF mRNAs were not
      detected by RT-PCR/Southern hybridization analysis of endometrial and ovarian
      total cellular RNA (tcRNA). Porcine SCF mRNA has been localized by in situ
      hybridization in porcine endometrial stromal tissue. Pregnancy does not appear to
      be a prerequisite for pSCF mRNA expression in endometrial tissue since it was
      detectable in tissue and tcRNA obtained from pregnant and nonpregnant gilts. The
      biological significance of uterine pSCF expression is currently unclear, but it
      probably participates in intracellular communication within the uterus.

PMID- 7508759
TI  - Water properties of hydrogel contact lens materials: a possible predictive model
      for corneal desiccation staining.
AB  - A set of properties of the water contained within hydrogel contact lens materials
      was determined with the aim of developing a model which would predict the
      propensity of a hydrogel contact lens material to induce corneal desiccation
      staining. We postulated that materials containing a larger proportion of water
      with the properties of bulk water would tend to induce corneal desiccation more
      readily than materials with the same overall water content but containing a
      larger proportion of water that interacts strongly with the polymer. The water
      structure [as measured by differential scanning calorimetry (DSC)] and the
      permeabilities of water and glucose were determined for a series of commercial
      hydrogel lenses. Both glucose permeability and DSC measurements are sensitive
      indicators of water structure and able to distinguish between various materials.
      To illustrate the potential of our model, the results of a short-term clinical
      study are presented. Lower levels of staining were noted for a material with a
      lower glucose permeability and a larger amount of water melting below 0 degrees C
      than for a control lens, even though both materials were similar in water content
      and water permeability. Further clinical studies are needed to validate this
      model.

PMID- 7508760
TI  - Autoclavable highly cross-linked polyurethane networks in ophthalmology.
AB  - Highly cross-linked aliphatic polyurethane networks have been prepared by the
      bulk step reaction of low molecular weight polyols and hexamethylenediisocyanate
      (HDI). These polyurethane networks are optically transparent, colourless and
      autoclavable amorphous glassy thermosets, which are suited for use in ophthalmic
      applications such as intraocular lenses and keratoprostheses. The properties of
      these glassy polyurethanes, obtained from the reaction of the low molecular
      weight polyols triisopropanolamine (TIPA) or tetrakis (2
      hydroxypropyl)ethylenediamine (Quadrol) and HDI in stoichiometric proportions,
      have been investigated in more detail. The glassy Quadrol/HDI-based polyurethane
      exhibits a reduction in ultimate glass transition temperature from 85 to 48
      degrees C by uptake of 1% of water, and good ultimate mechanical properties
      (tensile strength 80-85 MPa, elongation at break ca 15%, modulus ca 1.5 GPa). IR
      spectra of these hydrophobic polyurethane networks revealed the absence of an
      isocyanate absorption, indicating that all isocyanates, apparently, had reacted
      during the cross-linking reaction. The biocompatibility could be increased by
      grafting tethered polyacrylamide chains onto the surface during network
      formation. These transparent cross-linked polyurethanes did not transmit UV light
      up to 400 nm, by incorporation of a small amount of the UV absorbing chromophore
      Coumarin 102, and could be sterilized simply by autoclaving. They were implanted
      in rabbit eyes, either in the form of small circular disks or in the form of a
      keratoprosthesis (artificial cornea). It was shown that the material was well
      tolerated by the rabbit eyes. Serious opacification of the cornea, a direct
      result of an adverse reaction to the implant, was never seen. Even 1 yr after
      implantation of a polyurethane keratoprosthesis the eye was still 'quiet'.

PMID- 7508761
TI  - Hindered diffusion of high molecular weight compounds in brain extracellular
      microenvironment measured with integrative optical imaging.
AB  - This paper describes the theory of an integrative optical imaging system and its
      application to the analysis of the diffusion of 3-, 10-, 40-, and 70-kDa
      fluorescent dextran molecules in agarose gel and brain extracellular
      microenvironment. The method uses a precisely defined source of fluorescent
      molecules pressure ejected from a micropipette, and a detailed theory of the
      intensity contributions from out-of-focus molecules in a three-dimensional medium
      to a two-dimensional image. Dextrans tagged with either tetramethylrhodamine or
      Texas Red were ejected into 0.3% agarose gel or rat cortical slices maintained in
      a perfused chamber at 34 degrees C and imaged using a compound epifluorescent
      microscope with a 10 x water-immersion objective. About 20 images were taken at 2
      10-s intervals, recorded with a cooled CCD camera, then transferred to a 486 PC
      for quantitative analysis. The diffusion coefficient in agarose gel, D, and the
      apparent diffusion coefficient, D*, in brain tissue were determined by fitting an
      integral expression relating the measured two-dimensional image intensity to the
      theoretical three-dimensional dextran concentration. The measurements in dilute
      agarose gel provided a reference value of D and validated the method. Values of
      the tortuosity, lambda = (D/D*)1/2, for the 3- and 10-kDa dextrans were 1.70 and
      1.63, respectively, which were consistent with previous values derived from
      tetramethylammonium measurements in cortex. Tortuosities for the 40- and 70-kDa
      dextrans had significantly larger values of 2.16 and 2.25, respectively. This
      suggests that the extracellular space may have local constrictions that hinder
      the diffusion of molecules above a critical size that lies in the range of many
      neurotrophic compounds.

PMID- 7508762
TI  - The pore dimensions of gramicidin A.
AB  - The ion channel forming peptide gramicidin A adopts a number of distinct
      conformations in different environments. We have developed a new method to
      analyze and display the pore dimensions of ion channels. The procedure is applied
      to two x-ray crystal structures of gramicidin that adopt distinct antiparallel
      double helical dimer conformations and a nuclear magnetic resonance (NMR)
      structure for the beta6.3 NH2-terminal to NH2-terminal dimer. The results are
      discussed with reference to ion conductance properties and dependence of pore
      dimensions on the environment.

PMID- 7508763
TI  - Solvent history dependence of gramicidin-lipid interactions: a Raman and infrared
      spectroscopic study.
AB  - We have investigated the interactions between gramicidin and a model membrane
      composed of one phospholipid, dimyristoylphosphatidylcholine, as a function of
      the cosolubilization solvent and incubation time used in the sample preparation.
      Three organic solvents have been used; trifluoroethanol, a mixture of
      methanol/chloroform (1:1 v/v), and ethanol. Using Fourier transform infrared
      spectroscopy, we have demonstrated that the conformation adopted by gramicidin in
      the membrane is dependent upon the cosolubilization solvent used, and, only with
      trifluoroethanol, it is possible to incorporate gramicidin entirely as a beta 6.3
      helix. Moreover, Raman spectroscopy results indicate that the orientation of the
      tryptophan side chains in gramicidin and their interaction with the hydrocarbon
      chains and the carbonyl groups of the lipids are also dependent on the
      cosolubilization solvent. On the other hand, the effect of the incorporation of
      gramicidin on the thermotropism of the lipid bilayer was found to be dependent
      upon the conformation of gramicidin in the lipid bilayers.

PMID- 7508764
TI  - The effects of protons on 3',5'-cGMP-activated currents in photoreceptor patches.
AB  - Macroscopic 3',5'-guanine cyclic monophosphate (cGMP)-activated currents from
      photoreceptor outer segment membranes were examined as the pH on the cytoplasmic
      face of inside/out patches was reduced. In the absence of divalent cations,
      protons reduced the current in both directions without affecting the shape of the
      current-voltage relation consistent with a voltage-independent block. When Ca2+
      was added to the bath, increasing the [H+] relieved the Ca2+ block and eliminated
      the Ca(2+)-induced reversal potential shifts seen at pH 7.4. These results
      suggest that protons alter Na+/Ca2+ permeability of the channel and relieve Ca2+
      block of the sodium transport.

PMID- 7508765
TI  - [The antiatherosclerotic effects of a polysaccharide from raw animal stock].
AB  - The data obtained showed that the polysaccharide diminished the blood levels of
      cholesterol, beta-lipoproteins, and triglycerides, the concentrations of
      cholesterol in the liver and thoracic aorta in experimental atherosclerosis. It
      is concluded that the polysaccharide is promising in designing a new anti
      atherosclerotic drug.

PMID- 7508766
TI  - [NO-synthase inhibition induces a resistant pressor reaction during the 10-minute
      intravenous infusion of angiotensin-2 to narcotized rats].
AB  - With intact NO-synthase, the 10-minute intravenous infusion of angiotensin-2
      evoked the escape phenomenon from its pressor action. The intravenous infusion of
      the same dose of angiotensin-2 with the NO-synthase blocker (NG-monomethyl
      arginine) led to a stable pressor response, i.e. no escape phenomenon was
      observed. L-arginine restored the escape phenomenon from the pressor action of
      angiotensin-2 almost completely. The findings show that normal functioning of the
      endothelium relaxing factor (nitric oxide) generation system is significant for
      reduction of angiotensin-2 pressure action.

PMID- 7508767
TI  - [Placental-spermatic beta 2-globulin: its immunochemical identification,
      physicochemical characteristics and localization in the reproductive system].
AB  - A new antigen with beta 2-globulin mobility and M. W. of 20 kD, named placenta
      sperm beta-globulin (PSBG), was identified in human early placental tissue. Using
      immunodiffusion method, PSBG was found in the seminal plasma with the
      concentration about 120 mg/l, in the amniotic fluid 1-5 mg/l, in the liquor 1-10
      mg/l, and also in fetal kidney and stomach extracts. The examination of the male
      reproductive system revealed PSBG levels in the extracts of adults and fetus.

PMID- 7508768
TI  - [The effect of thyroid hormones and 5-azacytidine on the gene transcription of
      malic enzyme and 6-phosphogluconate dehydrogenase].
AB  - The effect of thyroid hormones and the methylation inhibitor 5-azacytidine on the
      level of expression of thyroid hormone-responsive genes (malic enzyme and 6
      phosphogluconate dehydrogenase genes) has been studied. DNA-RNA hybridization has
      shown there is an inverse correlation between the level of DNA methylation and
      gene expression of malic enzyme and 6-phosphogluconate dehydrogenase. Thus it
      suggests that the regulation of thyroid hormone gene expression can take place
      via DNA methylation blocking and that DNA demethylation is part of structural
      changes essential to the binding of thyroid hormones with DNA elements recognized
      by thyroid hormone receptors and to further induction of synthesis of specific
      mRNA.

PMID- 7508769
TI  - Interaction of human neutrophils and HL-60 cells with the extracellular matrix.
AB  - The accumulation of polymorphonuclear leukocytes (PMNs) at sites of inflammation
      or injury is generally attributed to the presence of chemoattractants and agents
      that increase PMN adherence. Extracellular matrix (ECM) proteins released at
      these sites may promote or modulate PMN adhesion, motility, oxidant generation,
      degranulation, and phagocytosis, but their role in these processes is not well
      defined. Of particular interest are thrombospondin (TSP), a 450 kD ECM protein
      released by activated platelets, and vitronectin (VN), a major constituent of
      plasma. Low concentrations of soluble TSP prime for both N-formyl-methionyl
      leucyl-phenylalanine (FMLP)-mediated O2- generation and chemotaxis, whereas VN
      suppresses FMLP-mediated O2- generation but primes for FMLP-mediated chemotaxis.
      TSP alone, at high concentrations, stimulates chemotaxis of PMNs, whereas VN, at
      the same concentrations, fails to stimulate chemotaxis. In contrast to soluble
      ECM proteins, substrate bound TSP, laminin, and VN promote PMN adhesion and
      random migration. As functional studies suggest, unactivated PMNs express
      receptors for both TSP and VN, and both TSP and VN receptor expression increases
      substantially following PMN activation. PMN-like HL-60 cells interact similarly
      with ECM proteins, and thus provide an important model for studying the
      expression of ECM receptors and the acquisition of ECM-mediated functional
      responses during blood cell differentiation. The ability of PMNs to interact with
      ECM proteins and modulate ECM protein receptors suggests that these proteins,
      alone or in synergy with chemotactic peptides, play an important role in
      regulating PMN diapedesis.

PMID- 7508770
TI  - Neutrophil adhesion to endothelial cells.
AB  - The emigration of neutrophils at sites of inflammation apparently requires
      intercellular adhesion. Initially, leukocyte adherence is observed in
      postcapillary venules where neutrophils roll along the luminal surface of the
      endothelial cells before stopping, changing shape, and migrating into the
      perivascular tissue. Recent evidence indicates that the adhesion molecules
      supporting the rolling phenomenon are distinct from those required for stopping
      and transmigration. The contribution of E-selectin (ELAM-1) to neutrophil
      adhesion and rolling was investigated using anti-E-selectin monoclonal antibody
      in an in vitro adhesion assay of isolated human neutrophils to murine L-cell
      monolayers stably transfected with human E-selectin cDNA. Isolated human
      neutrophils adhered to E-selectin expressing L-cell monolayers under
      physiological wall shear stress of 1.85 dynes/cm2 but not to untransfected L
      cells or ICAM-1 expressing L-cells. 47.8 +/- 6.0% of these adherent cells were
      rolling at an average rolling velocity of 10.6 +/- 1.7 microns/second. This
      adhesion and rolling was almost completely blocked by anti-E-selectin monoclonal
      antibody. Monoclonal antibody to L-selectin also reduced adhesion to E-selectin
      expressing cells by 70%. Chemotactic stimulation of neutrophils reduced both the
      number of adherent and rolling cells and the average velocity of the rolling
      cells without influencing the percentage of attached cells that were rolling.
      Pretreatment with anti-CD18 monoclonal antibody did not reduce the adhesion of
      the activated neutrophils but reversed the reduction in velocity caused by
      activation of these cells. The inhibitory potential of the anti-E-selectin
      monoclonal antibody was much less pronounced in adhesion of isolated neutrophils
      to human umbilical vein endothelial cell monolayers under conditions of flow and
      was limited to one third of the total adhesion. The proportion of the adherent
      neutrophils which transmigrated to the subluminal space of the endothelial cell
      monolayers was independent of pretreatment with anti-E-selectin monoclonal
      antibody.

PMID- 7508771
TI  - Analysis of the primary structure of insulin-like growth factor binding protein-3
      cDNA from Werner syndrome fibroblasts.
AB  - The mRNA encoding insulin-like growth factor binding protein-3 (IGFBP-3) is
      equally overexpressed in late-passage (old) normal human diploid fibroblasts
      (HDF) and in HDF derived from individuals with the premature aging disorder
      Werner syndrome (WS), relative to early-passage (young) normal HDF. However, the
      accumulation of IGFBP-3 protein in medium conditioned by WS cells is
      substantially less than in medium of old cells. In an attempt to understand this
      disparity between mRNA levels and protein output, we determined the nucleotide
      sequence of IGFBP-3 cDNA isolated from a WS cDNA library derived from mRNA of WS
      HDF, and compared it to three published normal IGFBP-3 DNA sequences. In the open
      reading frame, our results differed from one of the three sequences by a glycine
      substitution for alanine at residue 32. Minor differences in the 3'-untranslated
      region between the WS cDNA sequence and all three of the normal DNA sequences
      were also detected as 12 individual base substitutions and one adenine insertion.
      Thus, dampened accumulation of IGFBP-3 in medium conditioned by WS cells is not
      due to significant alterations in the sequence of the cognate mRNA.

PMID- 7508772
TI  - The combined effects of all-trans retinoic acid and granulocyte colony
      stimulating factor as a differentiation induction therapy for acute promyelocytic
      leukemia.
AB  - A 61-year-old male with acute promyelocytic leukemia (APL) had been in complete
      remission for the previous 15 months, but his APL relapsed with neutropenia.
      Although promyelocytes in bone marrow were reduced after administration of 60 mg
      all-trans retinoic acid (ATRA) daily, myelocytes were predominant on the
      myelogram and neutropenia did not recover. By adding 75 micrograms of granulocyte
      colony-stimulating factor (G-CSF) daily, neutrophils accounted for 35.0-55.5% of
      the myelogram, and the peripheral neutrophil count rose dramatically. Such
      morphological differentiation of myeloid series was also ascertained in terms of
      their functions of both neutrophil alkaline phosphatase activity and active
      oxygen producing capacity. This case supports the concept that G-CSF accelerates
      ATRA-induced neutrophilic differentiation of blast cells in APL.

PMID- 7508774
TI  - [Diagnosis and treatment with traditional Chinese medicine and Western medicine
      in infantile pneumonia].

PMID- 7508773
TI  - Low-dose interferon in chronic hepatitis non-A/non-B: effects on quantitative
      liver function and structure in a randomized, controlled multicenter trial.
AB  - In this randomized, controlled multicenter trial we evaluated the effects of
      recombinant interferon-alpha 2b on galactose elimination capacity and
      histological activity index in 88 patients with chronic active hepatitis non
      A/non-B. Forty-five patients were randomly assigned to treatment with interferon
      at 1.5 x 10(6) U three times per for 1 year; 43 patients were assigned to no
      treatment. A complete response (normalization of alanine aminotransferase) was
      observed, respectively, in 47% and 5% of the two groups (P < 0.006); 47% of these
      patients suffered a relapse. Thus 22% of patients had a sustained response.
      Histological activity decreased significantly in responders (P < 0.04) while the
      biopsy score did not change significantly in nonresponders. In contrast,
      galactose elimination capacity--a surrogate marker for survival in chronic active
      hepatitis--was not affected by response to treatment. None of the parameters
      evaluated, including hepatitis C virus RNA, was able to predict response or
      relapse. We conclude that low-dose interferon treatment for 1 year is as
      effective as the recommended treatment schedule.

PMID- 7508775
TI  - Morphological comparison between benign keratinizing cystic squamous cell tumours
      of the lung and squamous lesions of the skin in rats.
AB  - Approximately 700 cases of keratinizing cystic squamous lung lesions in rats were
      investigated by light microscopy in order to clarify the nomenclature and
      classification of these lesions. The structure of benign keratinizing cystic
      squamous cell tumours of the lung was compared to that of cystic squamous lesions
      in the skin of rats, with consideration of data from the literature. We conclude
      that the reviewed keratinizing cystic squamous cell lesions of the lung are true
      neoplasms and that the growth pattern of these cystic lesions is inconsistent
      with that of a simple cyst. In the development of squamous lung cancer, a
      continuum of proliferation from exaggerated metaplasia through benign cystic
      tumours to invasive squamous cell carcinomas can be observed.

PMID- 7508776
TI  - Urban family physicians and the care of cancer patients.
AB  - Members in the Department of Family Medicine of a university teaching hospital
      were surveyed to find out their involvement in caring for cancer patients.
      Respondents indicated that many cancer patients were followed, but few cancer
      support services in the hospital and the community were used. The desire to take
      on new cancer patients was lacking, yet an interest in continuing medical
      education existed. Feedback from the department will help guide our Education
      Committee to develop continuing medical education programs for family physicians
      caring for cancer patients.

PMID- 7508777
TI  - Reduction of Sephadex-induced lung inflammation and bronchial hyperreactivity by
      rapamycin.
AB  - Rapamycin is a macrolide antibiotic whose potent immunosuppressor activity was
      recently described in vivo and in vitro. The aim of the present work was to
      determine if rapamycin could affect an established inflammatory response.
      Conscious pathogen-free Dunkin-Hartley guinea pigs (300-400 g) were injected
      intravenously with Sephadex beads (G50, superfine, 10 to 40 microns, 24 mg/kg) to
      induce lung inflammation and bronchial hyperreactivity. Bronchoalveolar lavage
      (BAL) fluid was collected 2, 12 and 24 h after Sephadex administration and the
      cells were counted. Bronchial tissue was used to construct dose-response
      (contraction, g) curves to histamine and acetylcholine 24 h after the Sephadex
      injection, using a cascade system. Results are presented as area under the log
      dose-response curves. Test animals were injected with rapamycin (5 mg/kg) or its
      vehicle by the intramuscular route either 2 or 12 h after Sephadex injection and
      BAL fluid collected 24 h after Sephadex administration. Rapamycin administration
      2 h after Sephadex reduced eosinophil and lymphocyte numbers in BAL by 52 and
      55%, respectively, but not ex vivo bronchial hyperreactivity induced by Sephadex
      injection. However, rapamycin administration 12 h after Sephadex reduced BAL
      eosinophil and lymphocyte numbers (55 and 62%, respectively) and bronchial
      hyperreactivity. The increase in neutrophil numbers in BAL induced by Sephadex
      injection was not modified by rapamycin. Since lymphocyte numbers in BAL were
      significantly increased in Sephadex-treated animals at 12 h but not at 2 h after
      Sephadex injection, the present results suggest that the inhibition of bronchial
      hyperreactivity by rapamycin may be dependent on the presence of lymphocytes
      elicited into the airways by Sephadex injection.

PMID- 7508778
TI  - Reduction of endotoxin contamination of various crude vaccine materials by gram
      negative bacteria using aminated poly(gamma-methyl L-glutamate) spherical
      particles.
AB  - We describe a method for the removal of endotoxins from various crude antigen
      solutions originating from gram-negative bacteria using aminated poly(gamma
      methyl L-glutamate) (PMLG) spherical particles. The aminated PMLG adsorbents
      showed high affinity for various purified endotoxins at an ionic strength of mu =
      0.1. The endotoxin-adsorbing capacity of the adsorbent increased with increase in
      the amino-group content of the adsorbent. The adsorbent (3.2 meq/g amino-group
      content) showed the highest affinity for endotoxin at ionic strengths ranging
      from mu = 0.025-0.8. The adsorption of Bordetella pertussis antigen to the
      adsorbent decreased with increasing amino-group content of the adsorbent at an
      ionic strength of mu = 0.2. The adsorption of B. bronchiseptica protein to the
      adsorbent increased with increasing amino-group content of the adsorbent, but
      decreased with increasing ionic strength. The adsorbent (3.2 meq/g of amino-group
      content) selectively reduced endotoxin in crude antigen solutions originating
      from gram-negative bacteria, B. pertussis, B. bronchiseptica and Pasteurella
      multocida, even at a high ionic strength (mu = 0.2-0.4) without affecting the
      recovery of the protective antigens.

PMID- 7508779
TI  - Effect of partial outlet obstruction on contractility: comparison between severe
      and mild obstruction.
AB  - Detrusor dysfunction is one of the most common problems in patients with outflow
      obstruction secondary to benign prostatic hyperplasia. These patients complain of
      various symptoms, including urinary frequency, urge incontinence, difficulty in
      voiding, and retention. The severity of the symptoms is dependent on the stage of
      disease and/or severity of the obstruction. We compared the changes in the rat
      detrusor function following both mild and severe models of partial outlet
      obstruction in the rat. Outflow obstructions were created by ligation of the
      urethra over which a catheter was placed. The size of the catheter determined
      whether the severity of obstruction was mild or severe (1.70 mm for mild
      obstruction and 1.09 mm for severe obstruction). Changes in the bladder weight,
      length-tension relationships, and the contractile response to field stimulation,
      pharmacologic agonists, and KCl were studied in bladders isolated from 1 and 2
      week obstructed rats. Bladder weights of all obstructed rats increased
      significantly. The weight of the severe obstructed rats were significantly
      greater than rats subjected to mild obstruction. In general, passive length
      tension curves of obstructed rats were shifted to right. The magnitude of the
      active tension induced by high KCl was higher in the mild obstruction and lower
      in the severe obstruction. The maximum response to KCl of mild obstruction was
      generated at greater lengths than for the other groups. In general, the
      contractile responses of the mild obstructed bladder body to field stimulation,
      bethanechol, KCl, and ATP, and of the bladder base to field stimulation, KCl, and
      methoxamine, were significantly increased when compared to the responses of the
      control bladder body and base. However in the severe obstructed bladder, the
      responses to field stimulation, KCl, ATP, and methoxamine were significantly
      reduced from the responses of the control strips; the response to bethanechol was
      similar for control and the severe obstructed groups. In conclusion, the severity
      of outlet obstruction significantly altered the contractile response of the
      bladder. Mild obstruction induced a mild increase in bladder mass, which was
      associated with significant increases to all forms of stimulation. Severe outflow
      obstruction induced a substantial increase in bladder mass and a significantly
      greater reduction in the response to field stimulation than the response to
      bethanechol (which was unchanged).

PMID- 7508780
TI  - Prostate-specific antigen--a true progress in diagnosis and follow-up of prostate
      cancer.

PMID- 7508782
TI  - A brief review of ultrasensitive prostate-specific antigen assays for the
      evaluation of patients after radical prostatectomy.
AB  - The development of immunoassays for prostate-specific antigen (PSA) and their
      clinical utility are summarized. Because of the complexity of the PSA molecule
      and anti-PSA antibodies, there is currently no standard in PSA measurement.
      Evaluating various immunoassays requires the knowledge of the lower limit of
      detection as well as the biological and clinical thresholds of a given assay.
      There have been recent reports demonstrating earlier detection of residual
      prostate cancer after radical prostatectomy by ultrasensitive assays for PSA.
      Because of the recent evidence for non-prostatic sources of PSA such as the male
      urethra, the possibility of their contaminating PSA levels must be evaluated when
      more sensitive assays for PSA are under consideration.

PMID- 7508781
TI  - Structure, function, and regulation of the enzyme activity of prostate-specific
      antigen.
AB  - Prostate-specific antigen (PSA) and human glandular kallikrein 1 (hGK-1) are
      structurally similar products of the human glandular kallikrein gene locus on
      chromosome 19 that become selectively expressed by human prostate tissue. PSA is
      one of the most abundant prostate-derived proteins in the seminal fluid. The
      mature form of PSA, a single-chain glycoprotein of 237 amino acids, is a serine
      protease manifesting restricted chymotrypsin-like activity. PSA is mainly
      responsible for gel dissolution in freshly ejaculated semen by proteolysis of the
      major gel-forming proteins semenogelin I and II and fibronectin. PSA complexed to
      alpha 1-antichymotrypsin (ACT) is the predominant molecular form of serum PSA,
      although complex formation is slow between the purified proteins in vitro. PSA
      also forms stable complexes with alpha 2-macroglobulin (alpha 2M) in vitro, but
      as this results in encapsulation of PSA and complete loss of the PSA epitopes,
      the in vivo significance of this complex formation is presently unclear. A free,
      noncomplexed form of PSA constitutes a minor fraction of the serum PSA, although
      serum ACT occurs at large molar excess.

PMID- 7508783
TI  - Prostatic intraepithelial neoplasia and prostate-specific antigen.
AB  - Prostatic intraepithelial neoplasia (PIN) is a putative premalignant lesion of
      the prostate gland. PIN has been demonstrated to share morphologic and phenotypic
      similarities to invasive carcinoma of the prostate. In addition, PIN is spatially
      related to invasive carcinoma and occurs with greater frequency in men whose
      prostates harbor carcinoma. Prostate-specific antigen (PSA) is a glycoprotein
      produced by the prostatic epithelium. For PSA to be detected in the serum, it
      must traverse several tissue layers to reach the circulatory system. PSA levels
      associated with PIN are intermediate between those of benign and malignant
      prostate tissue. Spatially associated occult carcinoma, disruption of the basal
      cell layer, and increased vascularity may account for elevated PSA values in PIN.

PMID- 7508784
TI  - Efficient pathway for early detection of prostate cancer concluded from a 5-year
      prospective study.
AB  - In a prospective study the statistical characteristics of digital rectal
      examination (DRE), transrectal ultrasound (TRUS), and serologic determination of
      prostate-specific antigen (PSA) were assessed in 1230 patients aged over 40
      years. The sensitivity, specificity, and positive and negative predictive values
      were determined to be 80.3%, 69.7%, 58.9%, and 86.7%, respectively, for DRE;
      76.5%, 62.3%, 52.3%, and 83.1%, respectively, for TRUS; and 87.9%, 49.6%, 48.5%,
      and 88.3%, respectively, for PSA (normal level, 4 ng/ml). The data clearly
      demonstrate the nonsuitability of each single measure for reliable early
      detection of prostatic carcinoma. Connection of the parameters in all possible
      combinations under various conditions demonstrated the superiority of the test
      "DRE and PSA > 4 ng/ml" over DRE as the "gold standard" and all other options.
      The use of this approach as the first-line raster of an algorithm (outlined
      herein) would allow the detection of prostatic malignancy with a specificity of
      86.5% and a positive predictive value of 74.0%. Supplementing this screen with
      short-term controls in cases in which only one parameter is positive ("DRE or PSA
      > 4 ng/ml") might enable the detection of almost all patients with prostate
      cancer. TRUS did not provide any additional information.

PMID- 7508785
TI  - An algorithm for prostate cancer detection in a patient population using prostate
      specific antigen and prostate-specific antigen density.
AB  - Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of
      the prostate (CaP). However, its sensitivity and specificity are suboptimal,
      especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because
      benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in
      this range. This study was undertaken to determine the value of incorporating
      prostate volume measurements with serum PSA levels in a quotient (PSA/volume)
      entitled PSA density (PSAD). A total of 3140 patients were analyzed and
      stratified by serum PSA, digital rectal examination (DRE), transrectal prostate
      ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred
      for evaluation and therefore do not represent a screened population. Patients
      underwent prostate biopsies when abnormalities in TRUS or DRE were detected.
      Although both PSA and PSAD have statistical significance when the serum PSA value
      is < or = 4.0 ng/ml, neither has clinical significance in differentiating BPH
      from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability
      to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical
      significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is
      statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We
      conclude that all patients with an abnormality on DRE or TRUS should undergo
      prostate biopsy. If the PSA value is < or = 4.0 ng/ml, TRUS and PSAD are not
      warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1
      10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important.2_

PMID- 7508786
TI  - Prostate-specific antigen coordinated with digital rectal examination and
      transrectal ultrasonography in the detection of prostate cancer.
AB  - In a patient population, coordinated use of digital rectal examination and
      prostate-specific antigen can alert the physician as to the possible existence of
      prostate cancer. If both are used as first-line studies, abnormality of either
      can then direct the need for further study by transrectal ultrasonography and, in
      selected instances, prostatic biopsy. Such sequential use of these tests in a
      programmed manner results in an increased level of cancer detection as compared
      with use of the digital rectal examination alone.

PMID- 7508787
TI  - Prediction of tumor recurrence after radical prostatectomy using elimination
      kinetics of prostate-specific antigen.
AB  - The serum half-life of prostate-specific antigen (PSA) calculated subsequent to
      radical prostatectomy can serve to predict which patients are at high risk of
      bearing residual prostatic carcinoma despite their initial attainment of
      undetectable PSA serum levels. This report updates previous results to a mean
      follow-up period of 37 months. The initial results are essentially confirmed in
      that a mean PSA elimination half-life of 1.6 days in patients considered to be
      cured at least 24 months after prostatectomy provides additional useful
      information for predicting outcome in patients with potentially curable prostate
      cancer.

PMID- 7508788
TI  - Significance of androgen deprivation prior to radical prostatectomy, with special
      reference to prostate-specific antigen.
AB  - A total of 37 selected patients with clinical stage T2b or T3 prostate cancer
      received androgen deprivation prior to radical retropubic prostatectomy. A
      luteinizing hormone-releasing hormone (LHRH) analog alone was given to 15
      individuals; 19 received an LHRH analog with flutamide. Three underwent bilateral
      orchiectomy instead of chemical castration. The duration of androgen deprivation
      prior to radical prostatectomy varied from 3 to 16 months, with 31 individuals
      undergoing induction therapy for 3-6 months. Three received androgen deprivation
      for more than 1 year. In all, 15 patients had clinical stage T2b disease and 22,
      stage T3 prostate cancer. The prostate size decreased approximately 30%-50%
      following induction therapy. Prostate-specific antigen (PSA) values decreased in
      all 19 instances where this was obtained. In all, 6 of 15 (40%) patients with
      clinical T2b lesions and 9 of 22 (41%) with clinical T3 tumors had a positive
      surgical margin; 5 (13%) had 1 or more positive lymph nodes. Androgen deprivation
      was continued following surgery in 13 cases. Only one patient received
      postoperative radiation therapy. After a mean follow-up period of 33 months, 35
      (95%) patients are alive. Two patients died, one of poorly differentiated
      prostate cancer with subsequent metastasis and one of a myocardial infarction 33
      months after surgery without showing any evidence of disease. Of 23 patients
      without postoperative adjuvant therapy, 6 (26.1%) progressed (PSA level, > 0.4
      ng/ml). None of the patients who underwent adjuvant therapy progressed over a
      follow-up period of 6-75 months (mean, 38 months).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7508789
TI  - Prostate-specific antigen and androgen deprivation therapy.
AB  - Prostate-specific antigen (PSA) is a kallikrein-like serine protease that, for
      all practical purposes, is specific for prostatic tissue. PSA is usually detected
      at low concentrations (0.0-4.0 ng/ml) in the serum and is the most important
      tumor marker for detecting otherwise unsuspected prostate cancer; it also useful
      for monitoring the response of prostate cancer to various types of therapy.
      Androgen deprivation therapy (ADT) includes bilateral orchiectomy, luteinizing
      hormone-releasing hormone (LHRH) agonists, antiandrogens, and 5-alpha-reductase
      inhibitors. Treatment of benign prostatic hypertrophy (BPH) or prostate cancer
      with ADT usually decreases the serum PSA concentration. Recent basic science
      research has demonstrated that the expression of the PSA gene is controlled by
      androgens acting via the androgen receptor. Therefore, in some patients a low
      serum PSA concentration will be the result of hormonal down-regulation of the
      genetic expression of PSA and not the result of the antitumorigenic activity of
      the therapy. Nevertheless, in spite of the direct effect of ADT on PSA
      expression, PSA remains a valuable prostate cancer tumor marker for
      prognosticating the response to ADT and portending clinical progression after
      this type of treatment for most patients.

PMID- 7508790
TI  - Urodynamics in benign prostatic hyperplasia (BPH).
AB  - The simple pathophysiological concept of clinical BPH with a causal relationship
      between hyperplasia, obstruction, and specific symptoms does not hold up after a
      critical evaluation. The voiding function can nowadays be investigated
      comprehensively and differentiated utilizing modern urodynamic methods, and the
      function of the bladder outlet and the detrusor muscle can be evaluated
      quantitatively. Obstruction as a central term in clinical BPH can therefore be
      objectively documented. It can be shown that in a significant proportion of
      patients admitted for TURP with hyperplasia and symptoms of prostatism, no
      obstruction is present (over one-fourth of patients). The success rate of TURP in
      non-obstructed patients is worse than in obstructed patients; however, the
      subjective assessment of the surgical success is positive in the majority of
      patients. This holds true in a similar way for alternative treatment modalities
      (drug, balloon dilation, thermotherapy) after which the symptomatic success
      apparently is not associated with an objective reduction in obstruction. This
      lack of a definite correlation between symptoms and obstruction in BPH is open to
      many different interpretations. It is generally accepted that BPH without
      symptoms and obstruction or with obstruction but without symptoms may occur. It
      is, however, also true that aside from the highly selected patient population in
      this study with hyperplasia and symptoms and (suspected) obstruction, no data are
      available since urodynamic studies in patients with BPH but without symptoms are
      for obvious reasons not available. If we limit our thoughts to the few clear
      facts, it becomes evident that modern urodynamic methods can clearly distinguish
      between obstructive and non-obstructive symptomatic BPH. This introduces a new
      important standard of quality into BPH research requiring reassessment of
      currently available data. The simple urodynamics utilizing a flow rate recording
      as a convenient non-invasive diagnostic test is in widespread use and finds its
      proper place in the quick but non-specific documentation of bladder emptying
      function in clinical practice. Firm conclusions concerning the cause of a
      disturbed bladder emptying function are, however, not contained within the flow
      rate recording and can therefore not be abstracted from even the most refined
      methods to analyze the flow rate recording. The all-important parameter without
      which obstruction cannot be judged is the detrusor pressure during micturition.
      Since urodynamic pressure measurements are currently only possible as an invasive
      test, the indication for combined pressure flow measurements has to be considered
      carefully and the recording itself has to be conducted with appropriate
      expertise.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7508791
TI  - Carcinoma of the prostate: pitfalls in diagnosis.

PMID- 7508792
TI  - False positive values of PAP and PSA in complicated and non-complicated benign
      prostatic hypertrophy.
AB  - Cancer of the prostate has become the most frequent form of cancer in men.
      Different tests have been used in cancer of the prostate, including prostate acid
      phosphatase (PAP) and the prostate specific antigen (PSA). Their value as
      diagnostic screening is disputed, as it is known that there are false positives
      for both markers in benign prostate conditions. In order to explain their
      possible diagnostic value, we studied 112 patients with well-documented benign
      prostate hyperplasia. The data included in this study were: estimated weight,
      urinary infection, bladder catheter and histopathological study. By using as cut
      off 4 ng/ml for PAP and 10 ng/ml for PSA we found a percentage of false positives
      of 13% and 14% respectively. These percentages were in relation to the weight of
      the gland in each cases and in the case of PSA to the patient's clinical
      situation (infection, catheter).

PMID- 7508793
TI  - Photocrosslinking analysis of protein-RNA interactions in E. coli transcription
      complexes.
AB  - Regulation of transcription involves numerous specific protein-nucleic acid
      interactions. We have utilized photochemical crosslinking to identify
      interactions between Escherichia coli transcription proteins and the nascent RNA
      in several transcription complexes, including initiation, elongation, and
      antitermination complexes. We have developed new nucleotide analogs, 5-APAS-UTP
      and 5-APAS-CTP, which are tagged with photocrosslinking groups on base positions
      that do not interfere with normal Watson-Crick base-pairing. These analogs are
      incorporated at internal positions in RNA by E. coli RNA polymerase without
      disrupting RNA secondary structures. We have also used 8-azido-ATP, which can be
      incorporated uniquely into the 3' end of the RNA, to analyze interactions at the
      enzyme active site. Interactions between the RNA and the polymerase subunits, and
      the effect of various transcription factors, including NusA, NusB, NusE, and
      NusG, have been examined in complexes containing RNAs from 4 to approximately 80
      nucleotides. At almost every RNA position examined, both the beta and beta'
      subunits are contacted, but never the alpha subunit or NusA. An effect of NusA on
      the core labeling has been observed in some complexes, however. Sigma is
      contacted by nucleotides within three nucleotides of the +1 position on the DNA.

PMID- 7508794
TI  - The impact of Haemophilus influenzae immunisation on invasive infection in
      children.

PMID- 7508795
TI  - Use of halofantrine as standby treatment for malaria.

PMID- 7508796
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7508797
TI  - HIV transmission between children at home.

PMID- 7508798
TI  - Ice as a source of infection acquired in hospital.

PMID- 7508799
TI  - Classical light scattering for the determination of absolute molecular weights
      and gross conformation of biological macromolecules.

PMID- 7508800
TI  - Protecting groups in oligonucleotide synthesis.

PMID- 7508801
TI  - Extracting thermodynamic data from equilibrium melting curves for oligonucleotide
      order-disorder transitions.

PMID- 7508802
TI  - Incorporation of modified bases into oligonucleotides.

PMID- 7508803
TI  - Hyperamylasaemia in ruptured aortic aneurysm: incidence and prognostic
      implications.
AB  - A study was carried out to determine the incidence of increased serum amylase
      activity in patients with ruptured aortic aneurysm during the 48 h after
      presentation and to assess its clinical significance. In a prospective series of
      25 patients, hyperamylasaemia occurred in ten and was significantly associated
      with poor outcome (P = 0.005). In patients who died or had a major complication,
      serum amylase activity was significantly higher than in those who had an
      uncomplicated postoperative recovery (P < 0.05). There was a correlation between
      preoperative serum amylase activity and length of stay in the intensive care unit
      after operation (rs = 0.78 (95 per cent confidence interval 0.54-0.90), P <
      0.002). Serum amylase activity may be useful as a prognostic indicator in
      patients with ruptured aortic aneurysm.

PMID- 7508804
TI  - Prospective study of 713 below-knee amputations for ischaemia and the effect of a
      prostacyclin analogue on healing. Hawaii Study Group.
AB  - In 51 hospitals in six European countries 713 patients requiring below-knee
      amputation for ischaemic disease were studied prospectively. The patients were
      allocated randomly to receive standard postoperative treatment or standard
      treatment plus intravenous infusion of the prostacyclin analogue iloprost for 6 h
      per day over 14-21 days. Healing of the amputation stump and the need for
      reamputation at a higher level were similar in the two groups. Overall at 3
      months 59 per cent of stumps had healed, 19 per cent of patients had required
      reamputation at a higher level, 11 per cent had died and the remaining 11 per
      cent remained with unhealed stumps. Preoperative characteristics were analysed as
      possible risk factors or markers for primary healing, reamputation and death.
      Previous arterial reopening procedures (surgical or radiological) almost doubled
      the chances of primary stump healing (P < 0.05). The surgeon's assessment of the
      likelihood of healing was wrong in 21 per cent of cases in which the operating
      surgeon thought that healing would probably occur and in 52 per cent of those in
      which it was thought healing was improbable.

PMID- 7508806
TI  - Improving palliation for patients with gastrointestinal cancer.

PMID- 7508805
TI  - Adenocarcinoma of the duodenum: factors influencing survival. French Association
      for Surgical Research.
AB  - The records of 66 patients with histologically proven adenocarcinoma of the
      duodenum were reviewed retrospectively to determine factors influencing survival.
      The parameters studied were age, sex, weight loss, jaundice, anaemia, duodenal
      stenosis, type of surgical procedure, tumour size and location, depth of parietal
      invasion, presence and location of lymph node metastases, and pancreatic
      invasion. These factors were assessed in a group of 46 patients who underwent
      curative resection of the tumour; 20 patients who received palliative procedures
      were excluded from statistical analysis. Survival curves were established by the
      Kaplan-Meier method and compared by the Mantel-Haentszel test. The actuarial 3-
      and 5-year survival rates of patients undergoing curative resection were 59 and
      45 per cent respectively. None of the prognostic factors studied influenced
      survival. These results indicate that resection of adenocarcinoma of the duodenum
      should be performed whenever possible, even in the presence of lymph node
      metastasis and pancreatic spread.

PMID- 7508807
TI  - Differential effects of NBQX on the distal and local toxicity of glutamate
      agonists administered intra-hippocampally.
AB  - The ability of the non-NMDA glutamate antagonist NBQX (2,3-dihydroxy-6-nitro-7
      sulphamoyl-benzo(F)quinoxaline) to protect the brain against the neuronal death
      caused by glutamate agonists was examined. Glutamate agonists and NBQX were co
      injected into the dorsal region of the rat hippocampus and 4 days later the brain
      was examined histochemically for the loss of neurons. 95 nmol NBQX prevented the
      toxicity of glutamate agonists acting on the AMPA receptor (quisqualate and AMPA
      [L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate]), except for the higher
      dose of AMPA where toxicity was only partially reduced. This dose of NBQX also
      prevented about 50% of the toxicity of kainate, but produced a slight increase in
      the size of the lesions caused by NMDA (N-methyl-D-aspartate). With 190 nmol
      NBQX, a variable degree of non-specific damage resulted, but was mainly confined
      to the dentate region. Allowing for this damage, almost complete protection
      against the toxicity of non-NMDA glutamate agonists was obtained, with a partial
      protection against NMDA toxicity. Kainate, and a high dose of AMPA (2 nmol),
      consistently caused neuronal death in other limbic regions of the brain in
      addition to the hippocampal damage. About 50% of rats treated with 15 nmol
      quisqualate also showed damage to limbic regions. Both doses of NBQX prevented
      this distal damage caused by quisqualate, but not that caused by kainate. With
      AMPA, only the high dose of NBQX blocked the distal toxicity. Diazepam also
      blocked the distal toxicity of AMPA, but had only a minor effect on the
      hippocampal damage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508808
TI  - Evidence that corticotropin-releasing factor within the extended amygdala
      mediates the activation of tryptophan hydroxylase produced by sound stress in the
      rat.
AB  - Non-endocrine corticotropin-releasing factor (CRF) is believed to be involved in
      mediating stress behaviors in rats. The present study investigated the role of
      CRF in mediating the activation of tryptophan hydroxylase, the rate-limiting
      enzyme in serotonin synthesis, produced in response to sound stress. Bilateral
      injections of 0.5-3.0 micrograms of CRF directed towards the central nucleus of
      the amygdala increased tryptophan hydroxylase activity measured ex vivo when
      compared to vehicle-injected controls. This increase in enzyme activity, like
      that due to sound stress, was reversed in vitro by alkaline phosphatase. Intra
      amygdala CRF (0.5 microgram) also enhanced the in vivo accumulation of 5
      hydroxytryptophan (5-HTP) following the administration of m-hydroxylbenzylamine
      (NSD-1015, 200 mg/kg). The activation of tryptophan hydroxylase, produced by
      intra-amygdala CRF, was blocked by the CRF receptor antagonist alpha-helical CRF9
      41 (10 micrograms). Additionally, the 5-HT1A agonist, gepirone, given either
      systemically (10 mg/kg) or intracerebrally into the region of the dorsal raphe
      (14 micrograms), blocked the tryptophan hydroxylase response to CRF. CRF did not
      increase tissue levels of 5-hydroxyindole acetic acid (5-HIAA) or the ratio of 5
      HIAA to serotonin (5-HT) within the striatum of the same animals in which
      tryptophan hydroxylase activity was quantified, an effect produced by sound
      stress. Thus, while intra-amygdala CRF failed to mimic the sound stress response
      in its entirety, these data suggest that CRF is involved in mediating the
      activation of tryptophan hydroxylase produced by sound stress within the midbrain
      serotonin neurons.

PMID- 7508809
TI  - Intra-VTA infusions of the substance P analogue, DiMe-C7, and intra-accumbens
      infusions of amphetamine induce analgesia in the formalin test for tonic pain.
AB  - Experiments were designed to examine the analgesic effects of SP injected into
      the ventral tegmental area (VTA). Rats received bilateral intra-VTA infusions of
      3.0 micrograms/0.5 microliter/side of the SP analogue, DiMe-C7, or the vehicle,
      either immediately prior to or 25 min following an injection of 0.05 ml of 2.5%
      formalin into one hind paw. Formalin-induced pain responses were continuously
      recorded for 75 min. DiMe-C7 attenuated pain responses for approximately 30 min;
      the analgesia was more potent and longer-lasting when DiMe-C7 was infused after,
      rather than prior to, the early pain phase. In another set of experiments, rats
      were tested in the formalin test immediately following bilateral infusions of
      amphetamine (1.5 or 2.5 micrograms/0.05 microliter/side) into either the medial
      prefrontal cortex (mPFC) or the nucleus accumbens septi (NAS). Amphetamine failed
      to alter pain responses when infused into the mPFC, but both doses attenuated
      pain responses during 25 min when infused into the NAS. There was no evidence for
      pain inhibition in the tail-flick test for phasic pain following either intra-VTA
      DiMe-C7 or intra-NAS amphetamine. The finding that intra-VTA DiMe-C7 and intra
      NAS amphetamine produces analgesia in the formalin, but not the tail-flick test,
      suggests that activation of mesolimbic dopamine (DA) neurons contributes to
      suppression of tonic pain. Because stressors attenuate tonic pain responses, and
      are known to cause SP release in the VTA, we speculate that SP-induced activation
      of midbrain DA systems may mediate a form of pain- or stress-induced pain
      inhibitory system.

PMID- 7508810
TI  - Substance P containing polymer implants protect against striatal excitotoxicity.
AB  - The present study examined whether substance P (Sub P) could protect against
      quinolinic acid (QA)-induced lesions of the striatum, as measured by a loss of
      striatal D1 dopamine receptors. Sub P was extruded into Evac polymer rods for
      slow release. One 4 mm rod segment was implanted unilaterally into the striatum
      of each rat. One week later, animals received a striatal injection of QA (50, 75
      or 100 nmol/microliters) medial to the implanted rod. Controls received QA alone.
      Three weeks later, there was a dose-dependent loss of D1 receptors following QA.
      Sub P rods protected the striatum from QA-induced D1 receptor loss at this time.
      These results support the neuroprotection role of Sub P on excitotoxicity.

PMID- 7508811
TI  - Lidocaine suppresses the sodium current in Euhadra neurons which is mediated by
      cAMP-dependent protein phosphorylation.
AB  - The action of a local anesthetic, lidocaine, in association with the cyclic AMP
      (cAMP)-mediated intracellular biochemical process, was examined in identified
      Euhadra neurons. Lidocaine dose-dependently inhibited the inward current which
      was elicited by dibutyryl cAMP (db-cAMP) and isobutylmethylxanthine (IBMX). This
      inhibitory effect was transiently reversed by the intracellular injection of a
      catalytic subunit of a cAMP-dependent protein kinase. The inward current elicited
      by db-cAMP and IBMX was abolished by Na(+)-free saline but not by Ca(2+)-free
      saline. The data suggest that lidocaine is not acting directly on the Na+
      channel, but acts at a level proximal to the catalytic subunit of cAMP-dependent
      protein kinase.

PMID- 7508812
TI  - The phospholipase A2 inhibitor bromophenacyl bromide prevents the depolarization
      induced increase in [3H]AMPA binding in rat brain synaptoneurosomes.
AB  - We previously demonstrated that potassium (KCl)-induced depolarization of
      synaptoneurosomes prepared from rat telencephalon increased [3H]amino-3-hydroxy-5
      methylisoxazole-4-propionate ([3H]AMPA) binding to the AMPA receptor. In the
      present study, we determined the effects of inhibitors of various calcium
      dependent enzymes on this response to depolarization. Treatment of intact
      synaptoneurosomes with the phospholipase A2 (PLA2) inhibitor, bromophenacyl
      bromide (BPB), produced a marked and dose-dependent reduction in KCl-induced
      enhancement in [3H]AMPA binding. BPB had no significant effect on [3H]TPP
      accumulation in intact synaptoneurosomes, an index of membrane depolarization. In
      contrast to BPB, inhibitors of calcium-dependent kinases and proteases did not
      reduced the KCl-induced increase in [3H]AMPA binding. The results strengthen the
      hypothesis that phospholipase-induced modifications of AMPA receptor properties
      may be an important component of synaptic plasticity.

PMID- 7508813
TI  - Cyclothiazide decreases [3H]AMPA binding to rat brain membranes: evidence that
      AMPA receptor desensitization increases agonist affinity.
AB  - The effects of cyclothiazide, a drug which blocks AMPA (alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid) receptor desensitization, were tested on
      binding of [3H]AMPA to rat brain membranes. Cyclothiazide reduced [3H]AMPA
      binding by lowering the apparent affinity of the AMPA receptor. The magnitude of
      the decrease was temperature dependent and greater for membrane-bound than for
      solubilized receptors. These data provide evidence that desensitization increases
      the affinity of the AMPA receptor for agonists and indicate that a significant
      percentage of AMPA receptors in conventional equilibrium binding assays are in a
      desensitized state.

PMID- 7508814
TI  - [Antigen mimicry of anti-idiotypic antibodies for human ovarian carcinoma
      antigen: generation and characterization of anti anti-idiotype antibodies].
AB  - The antigen mimicry of monoclonal anti-idiotypic antibodies 6B11 and 1H12 was
      investigated, which carrying the internal image of human ovarian carcinoma
      antigen. Anti-anti-idiotypic antibodies, obtained from the mice immunized with
      6B11 or 1H12, binded to ovarian tumor antigen OC 166-9 specifically by enzyme
      linked immunosorbent assay (ELISA). Western blot analysis showed that Ab3 and Ab1
      recognized the same antigenic protein. Through antibody dependent cell-mediated
      cytotoxicity (ADCC), Ab3 sera killed the ovarian carcinoma cell line SKOV3
      specifically in vitro. These results suggest that 6B11 and 1H12 may substitute
      for the nominal antigen to stimulate a specific immune response and that they are
      potential candidates as idiotype vaccines against ovarian carcinomas.

PMID- 7508815
TI  - Activation of Cl- currents by intracellular chloride in fibroblasts stably
      expressing the human cystic fibrosis transmembrane conductance regulator.
AB  - The Cl- conductance of a mouse fibroblast cell line (LTK- cells) that was stably
      transfected with the human CFTR (cystic fibrosis transmembrane conductance
      regulator) complementary DNA was studied. Single Cl- channel activity was
      observed only after treatment of the cells with forskolin, the single-channel
      conductance being 6.2 +/- 0.2 pS with a linear current-voltage relationship. In
      CFTR+ cells, the whole-cell current at +90 mV increased from 7.3 +/- 2.7 pA/pF (n
      = 12) to 46.1 +/- 11.2 pA/pF (n = 5) after addition of dibutyryl-cyclic AMP (10(
      4) M) to the bath. Increasing the intracellular Cl- concentration to 150 mM
      activated linear Cl- currents in the absence of cyclic AMP in CFTR+ (n = 42) but
      not in CFTR- cells (n = 4). Similar Cl- current was also activated by high
      intracellular I- concentration. These results indicate that the CFTR-induced Cl-
      conductance in LTK- cells can be activated by either cyclic AMP or high
      intracellular halide concentrations.

PMID- 7508816
TI  - Significance of hepatocellular proliferation in the development of hepatocellular
      carcinoma from anti-hepatitis C virus-positive cirrhotic patients.
AB  - BACKGROUND: There is a hypothesis explaining the pathogenesis of carcinoma that
      increased proliferation of tissue cells correlates with the development of
      carcinoma, presumably by increased rate of random mutations and by promotion. In
      this study, the significance of hepatocellular proliferation in the development
      of human hepatocellular carcinoma (HCC) from anti-hepatitis C virus (HCV)
      positive cirrhotic patients was studied. METHODS: Twenty-eight Child A cirrhotic
      patients who were anti-HCV (C-100 antibody) positive were studied. At the
      beginning of the study, the in vitro uptake of bromodeoxyuridine (BrdU, a
      thymidine analogue) by hepatocytes in biopsied liver specimens was investigated
      as labeling indices (LIs), and they were divided into high-DNA synthetic (BrdU LI
      > or = 1.5%) and low-DNA synthetic (BrdU LI < 1.5%) groups. The patients were
      then surveyed prospectively with frequent ultrasonography (every 3 months) for
      the development of HCC for 3 years. RESULTS: The mean BrdU LI plus or minus
      standard deviation for 14 cirrhotic patients with high-DNA synthesis activity
      (BrdU LI > or = 1.5%) was 2.7 +/- 0.8%, and this was significantly (P < 0.001)
      higher than that for 14 cirrhotic patients with low-DNA synthesis activity (BrdU
      LI < 1.5%, 0.5 +/- 0.3%). Nine of 14 (64.3%) of the cirrhotic patients with high
      DNA synthesis activity developed HCC in the 3-year period, in contrast to only 2
      of 14 (14.3%) of the cirrhotic patients with low-DNA synthesis activity P <
      0.05).

PMID- 7508817
TI  - Incremental angiogenesis assessed by color Doppler ultrasound in the
      tumorigenesis of ovarian neoplasms.
AB  - BACKGROUND: The crucial role of angiogenesis in tumor behaviour has been studied
      extensively in vitro. The authors assessed the in vivo angiogenesis in ovarian
      neoplasms by color Doppler ultrasound and waveform analysis. METHODS: The
      intratumor artery resistance index (RI) of 222 ovarian neoplasms referred for
      color Doppler ultrasound evaluation was measured, and the corresponding
      histopathologic diagnosis was recorded. RESULTS: Satisfactory intratumor artery
      waveforms were obtained at an average of 1.12 sites in 44.7% (68 of 152) of
      benign tumors and at 6.28 sites in 97.1% (68 of 70) of the malignant group. Great
      heterogeneity in RI values existed. The RI of the intratumor artery in the benign
      group during the follicular phase (mean, 0.678) was significantly higher (P <
      0.001) than that of the luteal phase (mean, 0.414), epithelial ovarian carcinoma
      (n = 34; mean, 0.402), malignant germ cell tumor (n = 6; mean, 0.413), malignancy
      metastasized to the ovary (n = 18; mean, 0.357), and other rare malignancies (n =
      4; mean, 0.435). The RI of primary ovarian malignancy (n = 41; mean, 0.411) was
      significantly higher than that of malignancy metastasized to the ovary (P <
      0.05). The RI values of epithelium-originated neoplasms showed a significant
      incremental decrease from benign tumors (n = 48; mean, 0.695) toward borderline
      malignancy (n = 6; mean, 0.535; P < 0.01), early-stage ovarian carcinoma (n = 10;
      mean, 0.485; P < 0.01), and, finally, to advanced-stage ovarian malignancies (n =
      29; mean, 0.398; P < 0.05). CONCLUSIONS: Angiogenesis is a common phenomenon in
      malignant ovarian neoplasms, but the intensity of neovascularization may depend
      on individual tumor characteristics. The authors documented the incremental
      decrease of the resistance index in ovarian neoplasms, which may reflect the
      increase in angiogenesis intensity as an indication of malignant potential.

PMID- 7508818
TI  - Continuous infusion ABDIC therapy for relapsed or refractory Hodgkin's disease.
AB  - BACKGROUND: Patients whose Hodgkin's disease is refractory to standard
      combination chemotherapy usually have a poor prognosis. These patients are
      generally considered for bone marrow transplantation if the disease is still
      sensitive to chemotherapy. METHODS: Between May 1988 and January 1992, 19
      patients with refractory or relapsed Hodgkin's disease were treated with a
      regimen of doxorubicin, bleomycin, dacarbazine, lomustine, and prednisone
      (ABDIC). The ABDIC regimen as modified for continuous infusion by Hagemeister
      consisted of doxorubicin 25 mg/m2 by continuous infusion daily for 2 days,
      dacarbazine 200 mg/m2 by continuous infusion daily for 5 days, bleomycin 5 U/m2
      intravenously on days 1 and 5, CCNU 40 mg/m2 on day 1, and prednisone 40 mg/m2
      daily on days 1-5. Treatment was repeated every 28 days. RESULTS: At the time of
      treatment, mean age was 30.5 years (range 19-70), and time to ABDIC from initial
      diagnosis was 5.6 years (range 1-14). The mean number of prior chemotherapy
      regimens was 2.7 (range 1-5), and three of the patients had had autologous bone
      marrow transplantation before ABDIC: All patients had earlier received either
      mechlorethamine, vincristine, procarbazine, and prednisone or a regimen of
      doxorubicin, bleomycin, vinblastine, and dacarbazine, and 16 had received both.
      The mean number of ABDIC cycles was 3.9 (range 2-12). Total response rate was
      63%, with 10 patients having partial response and 2 having complete response of
      12 and 27 months' duration. Seven patients subsequently underwent bone marrow
      transplantation; two of these are free of disease at 35 and 41 months. The
      treatment was well tolerated; major toxicities were nausea and bone marrow
      suppression. CONCLUSION: ABDIC is an active and well tolerated therapy in
      patients with relapsed or refractory Hodgkin's disease, including those
      previously treated with ABVD. More importantly, perhaps, ABDIC as cytoreductive
      therapy followed by bone marrow transplantation offers the possibility of long
      term disease free survival in this heavily pretreated patient population.

PMID- 7508819
TI  - In vitro generation of human cytolytic T-cells specific for peptides derived from
      the HER-2/neu protooncogene protein.
AB  - The development of T-cell therapy for the treatment of human malignancy has been
      hindered, in large part, by a lack of identifiable tumor antigens. Studies to
      identify potential T-cell targets in humans have been difficult because of
      practical problems limiting the use of in vivo immunization and a lack of
      reproducible in vitro priming methods. Oncogenic proteins are involved in
      malignant transformation and maintenance of the transformed phenotype and
      theoretically are potential targets to T-cell therapy. HER-2/neu protein is a
      protooncogene product overexpressed in a variety of human malignancies and is
      associated with malignant transformation and aggressive disease in human breast
      cancer. Previous studies have shown that some patients with breast cancer have
      existent helper/inducer T-cell immunity to p185HER-2/neu protein and peptides.
      The current study represents initial attempts to identify candidate cytotoxic T
      lymphocyte (CTL) epitopes. Synthetic peptides were constructed identical to HER
      2/neu protein segments with amino acid motifs similar to the published motif for
      HLA-2.1-binding peptides. Four peptides were synthesized and two were shown to be
      avid binders to HLA-A2.1. Two of the four peptides could be shown to elicit
      peptide-specific CTL by primary in vitro immunization in a culture system using
      peripheral blood lymphocytes from a normal individual homozygous for HLA-A2.
      p185HER-2/neu protooncogene protein contains immunogenic epitopes capable of
      generating human CD8+ CTL. The identification of candidate CTL epitopes will
      allow studies to determine whether some cancer patients have existent CTL
      immunity to HER-2/neu protein. The demonstrated ability to generate human peptide
      specific CTL in vitro allows screening of other oncogenic proteins to identify
      candidate T-cell epitopes potentially useful for future immunotherapy studies.

PMID- 7508820
TI  - A sialyl-Le(x)-negative melanoma cell line binds to E-selectin but not to P
      selectin.
AB  - The adhesion molecules E-selectin (ELAM-1) and P-selectin (GMP-140/CD62)
      recognize the carbohydrate motives sialyl-Le(x), sialyl-diLe(x), or sialyl-Lea,
      though with different affinity. We found that the melanoma cell line NKI-4 bound
      to E-selectin, but not to P-selectin. This melanoma cell line did not express
      sialyl-Le(x), but was positive for sialyl-diLe(x) and sialyl-Le(a). In contrast,
      2 other melanoma cell lines, MeWo and SK-MEL-28, expressing either sialyl-diLe(x)
      or sialyl-Le(a) on the cell surface, bound neither E-selectin nor P-selectin.
      Transfection of the fucosyltransferases Fuc-TIII, Fuc-TIV, and Fuc-TV mediates
      cell surface expression of sialyl-Le(x) in many cell lines. We detected
      transcripts of the fucosyltransferases Fuc-TIII and Fuc-TV in 4 melanoma cell
      lines despite the absence of cell surface sialyl-Le(x). Our observations indicate
      that expression of fucosyltransferases (Fuc-TIII and -TV) and generation of cell
      surface sialyl-diLe(x) are not sufficient to permit adherence to E-selectin or P
      selectin. Furthermore, it seems possible that a yet undefined ligand different
      from sialyl-Le(x), sialyl-diLe(x), or sialyl-Le(a) enables melanoma cells to
      adhere to E-selectin.

PMID- 7508821
TI  - The degree of inhibition of protein tyrosine kinase activity by tyrphostin 23 and
      25 is related to their instability.
AB  - Tyrphostins, a series of compounds with hydroxy cis-cinnamonitrile backbone
      structures, are used as protein tyrosine kinase inhibitors to study signal
      transduction. While studying the inhibition of pp60c-src protein tyrosine kinase
      activity with tyrphostins 23 and 25 (3,4-di- and 3,4,5-trihydroxy cis
      cinnamonitrile), we found the inhibitors to be quite unstable. The inhibition of
      pp60c-src activity corresponded to the formation of products derived from the
      parent tyrphostin compound. One of these isolated products was at least 10-fold
      more inhibitory to both pp60c-src and epidermal growth factor receptor kinase
      activity than the parent tyrphostin. The generation of compounds more inhibitory
      than the parent tyrphostin may explain the delayed inhibition reported with
      epidermal growth factor receptor kinase activity. Since these tyrphostins are
      unstable and form compounds more inhibitory towards protein tyrosine kinase
      activity, any results obtained with these compounds must be interpreted with
      caution.

PMID- 7508822
TI  - Rapamycin selectively inhibits the growth of childhood rhabdomyosarcoma cells
      through inhibition of signaling via the type I insulin-like growth factor
      receptor.
AB  - We show that cell lines derived from childhood alveolar rhabdomyosarcoma (RMS)
      are very sensitive to the growth-inhibitory effects of the immunosuppressive
      agent rapamycin (RAP), compared to other human cell lines (50% inhibitory
      concentration range of 0.1-8 ng/ml, compared to 1280 to > 10,000 ng/ml). Our data
      suggest that the sensitivity of RMS lines is due to RAP inhibition of insulin
      like growth factor 1 receptor-mediated signaling, which is essential for
      continued proliferation of RMS cells. The embryonal RMS line Rh1, which was
      resistant to RAP in serum-containing medium (50% inhibitory concentration, 4180
      ng/ml), was highly sensitive under autocrine conditions of growth, indicating
      that resistance was due to paracrine signaling pathways insensitive to RAP
      action. FK506 reversed RAP action in all cell lines, indicating a dependence on
      complexing with the cytosolic FK506-binding protein for activity.

PMID- 7508823
TI  - Different splice variants of CD44 are expressed in gastrinomas but not in other
      subtypes of endocrine pancreatic tumors.
AB  - Endocrine pancreatic tumors are neuroendocrine neoplasms with malignant potential
      and give rise to varied clinical syndromes due to excessive secretion of multiple
      hormones. In this study 22 endocrine pancreatic tumors and 11 carcinoid tumors
      were examined for the expression of CD44 using a monoclonal antibody. CD44 gene
      activity of 11 endocrine pancreatic tumor tissues and five carcinoid tumor
      tissues was also studied by amplifying messenger RNA with the polymerase chain
      reaction followed by electrophoresis and blot hybridization. Strong
      immunoreactivity was detected on all gastrinomas examined (P < 0.001), and in two
      non-functioning endocrine pancreatic tumors. Such immunoreactivity was not
      observed in other subtypes of endocrine pancreatic tumors. In the normal human
      pancreas, the acinar portion and ductal epithelial cells stained strongly
      positive but pancreatic islet cells did not show any significant immunostaining.
      Furthermore, in endocrine pancreatic tumors with metastatic disease, CD44
      positive tumors had a tendency to metastasize to lymph nodes (P = 0.005), as
      compared with CD44-negative tumors which were locally invasive or metastasized to
      the liver. Although, in this limited material and short follow-up, we were not
      able to show any statistical significance, patients with CD44-negative endocrine
      pancreatic tumors had prolonged survival time compared with patients with CD44
      positive tumors (73% versus 59% at 5 years; P = 0.7). Of 10 carcinoid tumors
      examined, all three foregut carcinoids and one midgut carcinoid stained strongly
      positive, whereas all other midgut carcinoids were negative. Analysis of CD44
      splice variants showed that in all five gastrinomas there was overproduction of
      alternatively spliced larger molecular variants as compared with other types of
      endocrine pancreatic tumors and carcinoid tumors. The band pattern from one case
      of carcinoid tumor with a fulminant clinical course was similar to that of
      gastrinomas, whereas other carcinoid tumors expressed the epithelial form of
      CD44. The earlier identified splice variants which confer metastatic behavior on
      a pancreatic tumor cell line were not expressed in neuroendocrine tumors. Our
      data indicate that CD44 expression in endocrine pancreatic tumors correlates with
      the ability to give rise to lymph node metastases and may play a vital role in
      determining the fate of metastasizing cells. Moreover, because gastrin is not
      detectable in the normal human pancreas, the pancreatic ductal cell positivity
      for CD44 strengthened the ductal origin concept of gastrinomas. The band pattern
      of CD44 splice variants suggests that the previously described splice variants
      conferring metastatic behavior do not accompany metastatic activity of
      neuroendocrine tumors.

PMID- 7508824
TI  - Increased nitrosamine and nitrate biosynthesis mediated by nitric oxide synthase
      induced in hamsters infected with liver fluke (Opisthorchis viverrini).
AB  - We previously reported that increased endogenous nitrosation in human subjects
      infected with the liver fluke Opisthorchis viverrini in north-east Thailand could
      be a risk factor for the development of cholangiocarcinoma. In the present study
      we examined our hypothesis that this increased endogenous nitrosation is mediated
      by nitric oxide (NO) synthase induced by O. viverrini infestation. Syrian golden
      hamsters experimentally infected with O. viverrini liver fluke excreted in the
      urine significantly greater amounts of nitrate, a stable oxidization product of
      NO, than untreated hamsters (3.64 +/- 0.86 versus 2.64 +/- 0.60
      mumol/hamster/day, P < 0.001). When the rapidly nitrosatable thiazolidine 4
      carboxylic acid was administered orally, the infected hamsters also excreted
      significantly elevated levels of N-nitrosothiazolidine 4-carboxylic acid than
      untreated hamsters (4.27 +/- 2.20 versus 2.33 +/- 1.13 nmol/hamster/day, P <
      0.01), indicating that endogenous nitrosation is elevated in the animals with
      liver fluke. NO synthase activity measured in liver cytosol was about twice as
      high in the infected hamsters as in untreated animals. The enzyme, whose
      biochemical characteristics were similar to that induced in activated murine
      macrophages, was immunohistochemically localized in the cytoplasm of macrophages
      and eosinophils in the inflammation zone surrounding the parasite-containing bile
      ducts. These results support our hypothesis that, in fluke-infected subjects, NO
      synthase induction leads to excess production of NO and the observed elevated
      endogenous nitrosation. Since high concentrations of NO exert cytotoxic and
      mutagenic effects per se, excess NO produced in chronically infected/inflamed
      tissues may also play a role in initiation and subsequent modulation stages of
      cholangiocarcinoma development.

PMID- 7508825
TI  - Effect of 4-acetylaminofluorene and other tumour promoters on hepatocellular
      growth and binucleation.
AB  - The complete liver carcinogen 2-acetylaminofluorene (2-AAF) promoted the
      outgrowth of large neoplastic liver nodules and hepatocellular carcinomas in
      diethylnitrosamine-treated rats. 2-AAF did not alter the overall proliferative
      activity of normal hepatocytes, but suppressed binucleation and induced, on a
      long-term basis, an increase in proliferative activity and in the fraction of
      diploid hepatocytes relative to control animals. The analogue 4
      acetylaminofluorene (4-AAF) was much less effective than 2-AAF as a promoter of
      large nodules and carcinomas, but promoted the outgrowth of medium-sized nodules
      (1 < 2.5 mm). While 2-AAF specifically stimulated the growth of cells in enzyme
      altered foci, the cells responding to 4-AAF were more randomly distributed
      throughout the liver tissue. In contrast to 2-AAF, 4-AAF strongly stimulated the
      growth (DNA synthesis) of normal hepatocytes, but like 2-AAF it suppressed
      binucleation and caused a long-term increase in the proliferative activity and in
      the fraction of diploid hepatocytes. Other liver tumour promoters (cyproterone
      acetate, alpha-hexachlorocyclohexane, methylclofenapate) likewise stimulated the
      growth and suppressed the binucleation of normal hepatocytes. All hepatocellular
      ploidy classes were affected virtually equally by mitogenic stimulation, but at
      low proliferation rates the mononuclear cells were more proliferative than the
      binuclear cells. Since this difference could be eliminated by increasing the
      mitogen dose, it would seem that mononuclear cells may be somewhat more sensitive
      towards mitogens than binuclear cells. In contrast to previously reported results
      [Styles et al. (1990) Carcinogenesis, 11, 1149-1152], methylclofenapate was not
      found to specifically stimulate binuclear hepatocytes. Our results indicate that
      liver tumour promoters in general tend to induce a non-binucleating, non
      polyploidizing hepatocellular growth pattern, similar to that observed during
      liver regeneration. 4-AAF is confirmed to be, at best, a very weak promoter of
      liver carcinogenesis, but appears to be an effective promoter of benign tumours.

PMID- 7508826
TI  - Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable
      angina. European Cooperative Study Group.
AB  - BACKGROUND: Patients with unstable angina despite intensive medical therapy, ie,
      refractory angina, are at high risk for developing thrombotic complications:
      myocardial infarction or coronary occlusion during percutaneous transluminal
      coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that
      blocks the platelet glycoprotein (GP) IIb/IIIa receptor and potently inhibits
      platelet aggregation. METHODS AND RESULTS: To evaluate whether potent platelet
      inhibition could reduce these complications, 60 patients with dynamic ST-T
      changes and recurrent pain despite intensive medical therapy were randomized to
      c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion
      suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus
      injection followed by 10 micrograms/min for 18 to 24 hours until 1 hour after
      completion of second angiography and PTCA. During study drug infusion, ischemia
      occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay,
      12 major events occurred in 7 placebo patients (23%), including 1 death, 4
      infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an
      infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4
      placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but
      in none of the c7E3 Fab patients. Quantitative analysis showed significant
      improvement of the lesion in the patients treated with c7E3 Fab, which was not
      observed in the placebo group, although the difference between the two treatment
      groups was not significant. Measurement of platelet function and bleeding time
      demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction of ex vivo
      platelet aggregation to ADP, and a significantly prolonged bleeding time during
      c7E3 Fab infusion, without excess bleeding. CONCLUSIONS: Combined therapy with
      c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support
      the concept that effective blockade of the platelet GPIIb/IIIa receptors can
      reduce myocardial infarction and facilitate PTCA in patients with refractory
      unstable angina.

PMID- 7508827
TI  - Effect of acute magnesium administration on the frequency of ventricular
      arrhythmia in patients with heart failure.
AB  - BACKGROUND: There is a high incidence of ventricular arrhythmia and sudden death
      in patients with heart failure. Unfortunately, currently available antiarrhythmic
      agents have only limited efficacy and may result in proarrhythmia and hemodynamic
      deterioration in these patients. METHODS AND RESULTS: We studied the acute effect
      of intravenous magnesium chloride on the frequency and severity of ventricular
      arrhythmia in 30 patients with symptomatic heart failure using a double-blind,
      placebo-controlled crossover design. The left ventricular ejection fraction was
      23.0 +/- 8.0% (mean +/- SD). No patient had a history of symptomatic ventricular
      arrhythmia or was receiving antiarrhythmic agents, calcium channel antagonists,
      or beta-blockers. Patients were randomized to receive placebo (5% dextrose [D5W]
      in water alone) or magnesium chloride in D5W given as a bolus of 0.3 mEq/kg over
      10 minutes followed by a maintenance infusion of 0.08 mEq/kg per hour for 24
      hours. The magnesium concentrations 30 minutes and 24 hours after the bolus were
      3.6 +/- 0.1 and 4.2 +/- 0.1 mg/dL, respectively. There was no significant change
      in serum potassium concentration during magnesium administration. Blinded
      analysis revealed that administration of intravenous magnesium chloride, compared
      with placebo, significantly decreased total ventricular ectopy per hour (mean +/-
      SEM, 70 +/- 26 versus 149 +/- 64, P < .001), couplets per day (23 +/- 11 versus
      94 +/- 59, P = .007), and episodes of ventricular tachycardia per day (0.8 +/-
      0.2 versus 2.6 +/- 1.0, P = .051). CONCLUSIONS: Intravenous magnesium chloride
      administration reduces the frequency of ventricular arrhythmia in patients with
      symptomatic heart failure.

PMID- 7508828
TI  - Effects of beta-adrenergic blockade on immunologic and cardiovascular changes
      induced by mental stress.
AB  - BACKGROUND: Acute mental stress evokes responses in the cardiovascular and the
      immune systems. In particular, the subset of natural killer (NK) cells is found
      to be responsive to mental stress. The role of beta-adrenergic mechanisms in
      these processes in the subject of this investigation. METHODS AND RESULTS:
      Healthy male volunteers (n = 31) were subjected to two consecutive mental tasks.
      Subjects were randomly assigned to a beta-blocker (propranolol 40 mg) or a
      placebo group. The capsules were ingested 1 hour before the tasks. The tasks
      evoked sympathetic responses, as indicated by an increase in heart rate and a
      decrease in the preejection period. These effects were abolished under beta
      blockade, indicating that effective beta-blockade was achieved. In the immune
      system, significant increases were found for the number of NK cells and NK cell
      activity in the placebo group; these increases were absent in the propranolol
      group. In addition, an increase in all lymphocyte subsets was observed in
      subjects who had ingested propranolol. This increase, however, was also observed
      in subjects who had received propranolol but had not performed the tasks,
      indicating that these non-subset-specific increases in lymphocytes were a side
      effect of the beta-blocker. CONCLUSIONS: Mental stress induces activation of the
      sympathetic nervous system, with concomitant increases in the number of NK cells
      in the circulation. These changes were inhibited by propranolol, indicating that
      stress-induced increases in the number and activity of NK cells in the
      circulation are controlled by a beta-adrenergic mechanism.

PMID- 7508829
TI  - Modification of the dextran-Mg2+ high-density lipoprotein cholesterol
      precipitation method for use with previously frozen plasma.
AB  - Although dextran-Mg2+ precipitation produces accurate and precise results for
      high-density lipoprotein (HDL) cholesterol in fresh plasma and serum,
      precipitation of frozen specimens with triglycerides > 2.26 mmol/L (> 200 mg/dL)
      is difficult. We developed a modification that dilutes thawed samples by 35% and
      increases dextran-Mg2+ reagent to 15% of sample volume. Standard precipitations
      were performed on 62 fresh EDTA-treated plasma specimens; supernatant solutions
      were analyzed fresh and after freezing. Standard and modified methods were also
      performed on thawed, paired plasmas. In specimens with triglycerides < or = 2.26
      mmol/L, HDL cholesterol results for all methods were similar. For triglycerides >
      2.26 mmol/L, however, bias and precision were significantly affected by freezing,
      and 38.5% of samples with standard precipitation required additional procedures
      to produce clear supernatant solutions. HDL cholesterol concentrations for thawed
      samples with standard precipitation were significantly greater than for fresh
      samples (P < 0.02), but those for the modified method were not different from
      fresh samples, and only one specimen required additional steps to produce a clear
      supernate.

PMID- 7508830
TI  - Role of serotonin in the pathophysiology of depression: focus on the serotonin
      transporter.
AB  - Considerable evidence has accrued in the last two decades to support the
      hypothesis that alterations in serotonergic neuronal function in the central
      nervous system occur in patients with major depression. These findings include
      the following: (a) reduced cerebrospinal fluid (CSF) concentrations of 5
      hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin (5-HT) in
      drug-free depressed patients; (b) reduced concentrations of 5-HT and 5-HIAA in
      postmortem brain tissue of depressed and (or) suicidal patients; (c) decreased
      plasma tryptophan concentrations in depressed patients and a profound relapse in
      remitted depressed patients who have responded to a serotonergic antidepressant
      when brain tryptophan availability is reduced; (d) in general, all clinically
      efficacious antidepressants augment 5-HT neurotransmission following chronic
      treatment; (e) clinically efficacious antidepressant action by all inhibitors of
      5-HT uptake; (f) increases in the density of 5-HT2 binding sites in postmortem
      brain tissue of depressed patients and suicide victims, as well as in platelets
      of drug-free depressed patients; (g) decreased number of 5-HT transporter
      (determined with [3H]imipramine or [3H]paroxetine) binding sites in postmortem
      brain tissue of suicide victims and depressed patients and in platelets of drug
      free depressed patients. In our studies, this reduction in platelet 5-HT
      transporter binding is not due to prior antidepressant treatment of
      hypercortisolemia and is not observed in mania, Alzheimer disease, schizophrenia,
      panic disorder, fibromyalgia, or atypical depression. In a pilot study, this
      deficit predicted treatment response to an experimental antidepressant. These
      findings support the hypothesis that alterations in 5-HT neurons play a role in
      the pathophysiology of depression.

PMID- 7508831
TI  - Effect of hemoglobin F on measurements of hemoglobin A1c with physicians' office
      analyzers.

PMID- 7508832
TI  - The infra-red coagulator in the treatment of AIDS-related Kaposi's sarcoma and a
      comparison with radiotherapy.
AB  - Experience with 1 s pulses of the infra-red coagulator is reported for the
      treatment of 10 cutaneous AIDS-related Kaposi's sarcoma lesions in seven
      patients. The infra-red coagulator may be a useful addition in the palliative
      cosmetic treatment of Kaposi's sarcoma, producing an acceptable result in small
      (less than 2 cm in diameter) Kaposi's sarcoma lesions of the arms and trunk, but
      not in those situated on the legs.

PMID- 7508833
TI  - Transfusion-associated graft-versus-host disease--report of two further cases
      with an immunohistochemical analysis.
AB  - Transfusion-associated graft-vs.-host disease (tGVHD) is a severe disease usually
      affecting immunocompromised hosts with haematological neoplasia. Two patients
      with acute leukaemia are reported, who developed fatal tGVHD after blood
      transfusions. Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion
      molecule 1 (VCAM-1) and endothelial leucocyte adhesion molecule 1 (ELAM-1)
      expression and the CD4/CD8 ratio were assessed in lesional skin. ICAM-1 was
      strongly expressed on epidermal keratinocytes and endothelial cells (EC) and
      correlated with HLA-DR staining. VCAM-1 was strongly expressed on EC in the
      superficial dermal vessels. ELAM-1 stained weakly on EC in some of the
      superficial vessels. CD8+ lymphocytes showed prominent epidermotropism; the
      CD4/CD8 ratio was 0.8 in case 1 and 1.2 in case 2. Infiltrating cells were
      positive for CD3, CD11a, and CD18. Langerhans' cells were almost completely
      absent. The dermatologist must be aware of the importance of such a rare,
      unexpected and almost always fatal complication of blood transfusion, in order to
      make an early diagnosis. Irradiation of blood products is the only effective way
      to prevent tGVHD in all subjects at risk.

PMID- 7508834
TI  - The number of CD1a+ large low-density cells with dendritic cell features is
      increased in the peripheral blood of HIV+ patients.
AB  - Employing a discontinuous Percoll gradient following Ficoll-Hypaque separation of
      peripheral blood mononuclear cells from normal subjects (n = 14) and patients
      with HIV-1 infection (n = 50), we separated a population of low-density cells
      consisting of monocytoid cells, lymphocytes, and some granulocytes. In cytospin
      preparations, less than 5% of the monocytoid cells were positive for nonspecific
      esterase and CD14. However, CD1a was positive in 5-20% of these cells.
      Ultrastructurally, CD1a-labeled immunogold particles were demonstrated on the
      monocytoid cells which bore some features of dendritic cells. Flow cytometry of
      the low-density cells identified a subset of buoyant, large cell population,
      which excluded lymphocytes. This large low-density cell (LLDC) population was
      significantly expanded in patients with HIV infection and comprised 32.3 +/-
      21.3% of low-density cells compared to 7.0 +/- 2.8% in normal subjects (P <
      0.0001). Of the LLDC population 45.2 +/- 23.4% were CD1a+ in patients compared to
      17.5 +/- 13.3% in normal subjects (P < or = 0.0001). HLA-DR and HLA-DQ were
      coexpressed in approximately 70 and 50% of these CD1a+ LLDC, respectively. A
      simple nonculture assay method employed by us facilitates rapid screening of
      infected blood specimens for the CD1a+ large low-density cells with dendritic
      cell features, which could be an additional parameter to monitor HIV disease
      progression.

PMID- 7508835
TI  - Human T lymphocyte subpopulation and NK cell alterations in persons exposed to
      cocaine.
AB  - Immunophenotypic changes in peripheral blood mononuclear cells were analyzed by
      flow cytometry in several patient groups positive for cocaine in their urine.
      Single- and dual-color immunofluorescence staining was performed to examine total
      numbers of NK, T, and B cells, as well as the coexpression of surface molecules
      on T cells associated with memory function, helper/inducer capacity, and
      activation status. In addition, levels of several serum proteins (including
      immunoglobulins) and other demographic variables were evaluated. Our results show
      that cocaine-intoxicated patients display reductions in the total percentage of
      CD4+ T cells and increases in the number of NK cells. Dramatic shifts within
      certain T cell subpopulations were also observed. In particular, there appeared
      to be a preferential stimulation of "activated" T cells as indicated by increased
      levels of class II+ CD4 and CD8 T cells and IL2r+ CD4 T cells. "Memory" CD8+ T
      cell subpopulations (i.e., CD45RO+) were reduced in the cocaine-positive
      patients, whereas CD45R+/CD8+ T cells were accordingly increased in the same
      individuals. In some cases, direct correlation could be established between
      certain T cell percentages and cocaine levels. None of the serum protein levels
      measured appeared to be influenced by cocaine. These findings demonstrate that
      cocaine utilization is associated with variations in levels of certain T cell
      subpopulations and other immune cells. This may represent a disruption of
      particular immunologic cell networks which could ultimately influence host
      resistance to infection and malignancy.

PMID- 7508836
TI  - Comparison of properties of murine monoclonal anti-idiotypic antibodies generated
      with idiotype-bearing monoclonal antibodies to myelin basic protein peptides or
      their complementary peptides.
AB  - The present study was undertaken to compare the features of monoclonal antibody
      (mAb) anti-idiotope (Id) induced by complementary peptides, synthesized on the
      basis of inverted hydropathy for a myelin basic protein (MBP) peptide, or by
      conventional methodology using Id-bearing antibodies to the same MBP peptide as
      immunogen. The six reagents studied consisted of mAbs reactive with MBP peptide
      acetyl 1-9 and MBP peptide 80-89 and anti-Id reagents against these two mAbs
      prepared by either the complementary peptide or the conventional approach. ELISA,
      immunoblotting, immunoinhibition of hybridoma cell production of Id-bearing mAb
      to MBP, and FACS indicated that the anti-Ids generated by either technique were
      similar although existing in a range reflecting biologic phenomena. mAbs anti-Id
      prepared by either method continued to show an IgM isotype preference, possibly
      related to technical considerations, and continued to recognize a cross-reactive
      Id on the kappa light chain of the mAbs to MBP peptides acetyl 1-9 and 80-89.
      There was no indication that the anti-Ids prepared by the complementary peptide
      approach were restrictive or selective in a manner different from those made by
      the conventional approach.

PMID- 7508838
TI  - Minimal requirements for hematologic cytochemistry in the community hospital
      laboratory.
AB  - In the current atmosphere of increasing fiscal awareness, laboratorians are
      carefully assessing which procedures should be performed in-house and which
      should be sent to a reference laboratory. Ultimately these decisions are based
      not only on cost but also on the patient population serviced and on technical and
      workload considerations in the individual laboratory. A simple rule of thumb is
      to be able to perform stains that are either needed frequently or are very easy
      to perform and interpret if needed emergently. In choosing which staining
      procedure should be sent to a reference laboratory, it is helpful to understand
      both utility of the procedure and its special handling requirements, such that
      the best possible information can be obtained for diagnostic purposes.

PMID- 7508837
TI  - The Ehrlich-Chenzinsky-Plehn-Malachowski-Romanowsky-Nocht-Jenner-May-Grunw ald
      Leishman-Reuter-Wright-Giemsa-Lillie-Roe-Wilcox stain. The mystery unfolds.
AB  - This article gives a brief history of the evolution of the modern blood stain.
      Current theories of molecular mechanisms involved in the staining process are
      also reviewed.

PMID- 7508840
TI  - Regulation of adhesion and adhesion molecules in endothelium by transforming
      growth factor-beta.

PMID- 7508839
TI  - Migration of activated lymphocytes.

PMID- 7508841
TI  - CD44 and other cell interaction molecules contributing to B lymphopoiesis.

PMID- 7508842
TI  - CD44: a multitude of isoforms with diverse functions.

PMID- 7508843
TI  - The selectins and their ligands.

PMID- 7508844
TI  - [The incidences of benign prostatic hyperplasia and prostatic cancer in China].
AB  - Step-sections of 321 prostatic specimens from unselected autopsies were examined
      in order to understand the incidences of benign prostatic hyperplasia (BPH) and
      prostatic cancer (CaP) in China. The results showed that the incidence of BPH in
      patients of 51-60, 61-70, 71-80, and 81-90 years old was 20%, 50%, 57.1% and
      33.3% respectively. The incidence of latent CaP in the above-mentioned age
      series, including 60 prostatic specimens from cystoprostatectomies was 9.3%,
      5.7%, 26.9% and 16.7% respectively. The Incidence of CaP in BPH surgical
      specimens was 33/676 (4.9%). The histological incidences of BPH and CaP in China
      were similar to or half of that of western world. But the epidemiological
      incidence of CaP in China was only 1/20-1/30. Further investigation about this
      condition is necessary.

PMID- 7508845
TI  - [Microwave hyperthermia for benign prostatic hyperplasia].
AB  - We treated 312 cases of benign prostatic hyperplasia (BPH) with 915 MHz microwave
      delivered transurethrally with a special applicator. All the 312 patients
      received a single thermal session (60 minutes). The temperature achieved in the
      prostate ranged from 43 to 45 C. Follow-up for 6 months showed that about 70.1%
      of the patients were subjectively improved and 37.0% had a increased flow rate,
      43.0% gained a decreased residual urine. In 32 failure cases, 11 were due to
      median lobe hyperplasia, 4 diabetes mellitus, 4 cerebrovascular disease, and 13
      miscellaneous. In the full retention group (39 patients), 21 had catheter removed
      2-7 weeks after the thermal session. In this group, 27 patients encountered a
      side effect, including hematuria 23, fever 2, and acute retention 2, all of these
      patients were recovered rapidly.

PMID- 7508847
TI  - [Prostatic carcinoma].

PMID- 7508846
TI  - Quantitative detection of hepatitis C virus genome in liver tissue and
      circulation by competitive reverse transcription-polymerase chain reaction.
AB  - We quantified hepatitis C virus RNA in 25 Japanese patients with chronic type C
      liver disease by competitive reverse transcription-polymerase chain reaction. The
      amount of the viral RNA in the serum (2 x 10(5)-2 x 10(8) copies/ml) correlated
      with that in the liver tissue (10(8)-10(11) copies/g) (N = 23, r = 0.727, P <
      0.0001). One gram of the infected liver tissue contained 10(2)-10(4) (geometric
      mean, 10(3), N = 23) times as many copies of the viral RNA as did 1 ml of the
      serum. Liver tissues of chronic aggressive hepatitis contained significantly
      higher amounts of the viral RNA than those of chronic persistent hepatitis (P <
      0.05). These observations suggested that this method is useful to evaluate viral
      amount, and the amount of the circulating hepatitis C virus RNA could be used as
      a marker of the intrahepatic viral amounts, which might contribute to disease
      activity.

PMID- 7508848
TI  - Neurological dysfunction in asymptomatic HIV-1 infected men: evidence from evoked
      potentials. HNRC Group.
AB  - Neurological function in 159 subjects infected by the human immunodeficiency
      virus (HIV) who had no neurological symptoms or signs (129 asymptomatic, 30 with
      ARC/AIDS) was compared to that of 62 controls by means of pattern-reversal evoked
      potentials (PREPs), brain-stem auditory evoked potentials (BAEPs), median nerve
      somatosensory evoked potentials (MSEPs), tibial nerve somatosensory evoked
      potentials (TSEPs) and nerve conduction studies (NCSs). Central nervous system
      somatosensory conduction from lumbar cord to cortex was prolonged in both
      asymptomatic seropositive and ARC/AIDS groups, while peripheral somatosensory
      conduction, NCSs and PREP delays occurred only in the ARC/AIDS group. BAEPs did
      not show significant differences among groups. TSEPs were abnormal in 8% of
      asymptomatic carriers and 43% of patients with ARC/AIDS, MSEPs in 7% and 20%,
      PREPs in 4% and 0%, and BAEPs in 1% and 0% respectively. One or more evoked
      potentials were abnormal in 18 of 129 (14%) asymptomatic carriers and 13 of 30
      (43%) subjects with ARC/AIDS as compared with 1 of 62 (2%) seronegative controls.
      We conclude that asymptomatic HIV carriers have subclinical neurological
      impairment of central somatosensory function and that the neurological impairment
      increases with disease progression to involve peripheral nerves and visual
      system.

PMID- 7508850
TI  - Click-evoked responses from the exposed intracranial portion of the eighth nerve
      during vestibular nerve section: bipolar and monopolar recordings.
AB  - We compare the click-evoked compound action potentials from the exposed
      intracranial portion of the eighth nerve using bipolar and monopolar recording
      electrodes in patients undergoing vestibular nerve section. It is assumed that a
      bipolar recording electrode will only record propagated neural activity in the
      auditory nerve, whereas a monopolar recording electrode may in addition record
      electrical activity that is conducted passively to the recording site. The
      results of the present study confirm that the earliest detectable propagated
      neural activity in the intracranial portion of the auditory nerve occurs with a
      latency that is close to that of peak II of the brain-stem auditory evoked
      potentials, and the results also confirm that the late components in the click
      evoked compound action potentials that have been demonstrated previously using
      the monopolar recording technique represent propagated neural activity in the
      auditory nerve. The results also indicate that the responses that are recorded by
      a bipolar recording electrode, when the small tips of which are placed on the
      eighth nerve when it is relatively dry, represent only small populations of nerve
      fibers. Even when an attempt is made to align the two tips of a bipolar electrode
      with the course of the auditory nerve, this type of electrode may record from
      different populations of nerve fibers.

PMID- 7508849
TI  - Effects of chronic high serum levels of phenobarbital on evoked potentials in
      epileptic children.
AB  - We studied VEP and BAEP in 8 epileptic children with chronic high serum levels of
      phenobarbital. Records were obtained when the drug serum level was more than 40
      mg/l and repeated when serum concentration was within the normal range. During
      the periods of high levels, P2 latency of the VEP was abnormally increased in all
      cases but one. The mean P2 latency decreased according to the reduction of the
      serum level of phenobarbital (139.6 msec vs. 110.1 msec, P = 0.002), and a
      significant regression coefficient (r = 0.546, P = 0.0271) was also noted between
      P2 latency and drug serum concentration. BAEPs were normal in all cases but one,
      who had a coexisting high level of phenytoin. All these findings suggest that the
      pharmacological effect of phenobarbital may be detected by VEPs and may result in
      delay of the P2 component.

PMID- 7508851
TI  - Speech-evoked activity in primary auditory cortex: effects of voice onset time.
AB  - Neural encoding of temporal speech features is a key component of acoustic and
      phonetic analyses. We examined the temporal encoding of the syllables /da/ and
      /ta/, which differ along the temporally based, phonetic parameter of voice onset
      time (VOT), in primary auditory cortex (A1) of awake monkeys using concurrent
      multilaminar recordings of auditory evoked potentials (AEP), the derived current
      source density, and multiunit activity. A general sequence of A1 activation
      consisting of a lamina-specific profile of parallel and sequential excitatory and
      inhibitory processes is described. VOT is encoded in the temporal response
      patterns of phase-locked activity to the periodic speech segments and by "on"
      responses to stimulus and voicing onset. A transformation occurs between
      responses in the thalamocortical (TC) fiber input and A1 cells. TC fibers are
      more likely to encode VOT with "on" responses to stimulus onset followed by phase
      locked responses during the voiced segment, whereas A1 responses are more likely
      to exhibit transient responses both to stimulus and voicing onset. Relevance to
      subcortical speech processing, the human AEP and speech psychoacoustics are
      discussed. A mechanism for categorical differentiation of voiced and unvoiced
      consonants is proposed.

PMID- 7508852
TI  - Mapping P300 waves onto inhibition: Go/No-Go discrimination.
AB  - Subjects viewed letters presented at 2 sec intervals and prepared a fast button
      press whenever an "O" appeared. If the next letter was an "X" the button press
      was executed (Go signal), but if the letter was a non-X character (T, H, Z)
      suppression of the response was required (No-Go cue). No-Go signals elicited a
      P300-like wave that was larger at central and frontal scalp sites contralateral
      to the prepared movement, compared to P300s elicited by Go cues which were
      symmetric about the sagittal midline and dominant at parietal sites. Subtraction
      of preparatory CNVs from the No-Go P300 did not remove differences in scalp
      topography, or reduce the amplitude of the No-Go P300 to that seen following
      control letters that required perceptual identification but did not call for
      suppression of prepared motor responses. Principal components analysis identified
      a middle positive wave following X-alone control stimuli whose topography
      resembled the No-Go P300. These findings suggest that the source of augmented No
      Go P300s is a generator involved with sensorimotor inhibition. We discuss the
      mechanism of P300 waves and evidence linking these waves with inhibition in other
      task arrangements.

PMID- 7508853
TI  - Characteristics of the background fields in multichannel-recorded magnetic field
      responses.
AB  - We have studied the background fields in the auditory evoked magnetic field
      responses recorded with a 37-channel SQUID magnetometer. The background fields
      were found to have a main contribution from the spontaneous fields, which
      originate in the neural activities of the brain. The spontaneous fields had
      strong spatial correlation across the recording sites even after averaging over
      100 epochs. The spatial distribution of the spontaneous fields consisted of 3
      main components of single extremum pattern, dipolar pattern, and a dipolar
      pattern with some distortion. Computer simulations of the localization of a
      single dipole source of the evoked field response showed that the spontaneous
      background field could bring about large location errors in an unpredictable
      manner, as compared with the location errors caused by a spatially random
      Gaussian noise field.

PMID- 7508854
TI  - Contrast modulated steady-state visual evoked potentials (CMSS VEPs): recording
      evoked potentials and related single cell responses in area 17 of the cat.
AB  - (1) The functional characteristics of the neuronal substrate, responding to the
      CMSS VEP stimulus, were studied by recording CMSS VEPs and related single unit
      activity in area 17 of the anaesthetised and paralysed cat. CMSS VEPs use an 8 Hz
      phase reversing (i.e., 16 reversals/sec) grating stimulus with rapid contrast
      sweeping and allow the contrast thresholds and lag values to be measured as a
      function of the spatial frequency. (2) The CMSS VEPs of the anaesthetised cat
      have a wave form similar to those of humans but are shifted to lower spatial
      frequencies, higher contrast thresholds and longer lag values. (3) The cellular
      response to a sinusoidal grating, phase reversing at 8 Hz, was studied in order
      to identify the neuronal substrate generating the CMSS VEPs. Sixty percent of the
      area 17 cells respond to this stimulus. Cells responding at 8 Hz reversal
      comprise a distinct subpopulation of visual cortical cells selective for higher
      velocities and lower spatial frequencies. (4) Although the CMSS VEPs contain
      almost exclusively energy at 16 Hz, the temporal response pattern of striate
      cells is quite disparate, including first and second harmonic response patterns
      as well as an intermediate type. (5) There is a near-perfect correlation between
      the contrast thresholds of single cells, obtained with the contrast swept
      stimulus and those obtained with a static contrast test, validating the technique
      of rapid linear contrast sweeping. (6) The influence of the temporal parameters
      of the contrast sweeping on the calculated contrast threshold was investigated at
      the neuronal level. These parameters only marginally influence the responses. (7)
      CMSS VEP contrast thresholds and neuronal thresholds were compared. The
      sensitivity of VEPs corresponds to that of the most sensitive neuronal
      generators. CMSS VEP lag values are longer than the values for individual
      neurones.

PMID- 7508855
TI  - Induced refractive errors and pattern electroretinograms and pattern visual
      evoked potentials: implications for clinical assessments.
AB  - Refractive errors were induced in normal subjects by means of positive dioptre
      lenses to reduce visual acuity (VA) from an initial level of 20/20 to 20/100 and
      then to 20/200. Pattern electroretinograms (PERGs) and pattern visual evoked
      potentials (PVEPs) were simultaneously recorded at each of these 3 levels of VA
      using high contrast checkerboard stimuli subtending 11' and 42' of visual arc.
      Attention was paid to PERG and PVEP variables used for clinical assessments. The
      findings confirmed the need to take refractive errors into account because, in
      some cases, latencies and particularly PERG amplitudes fell outside normal limits
      with decreased VA, especially when using smaller checks.

PMID- 7508856
TI  - Spinal and brain-stem SEPs and H reflex during enflurane anesthesia.
AB  - Whereas cortical SEPs are altered by halogenated anesthetics, spinal and
      subcortical SEPs are thought to be hardly affected. In this study the spinal N13
      potential (recorded with anterior neck reference) showed a significant delay with
      enflurane anesthesia. The P13 and P14 far-field potentials, however, remained
      unchanged. Our results indicate that oligosynaptic as well as polysynaptic
      pathways are influenced by halogenated anesthetics and that enflurane has
      different effects on spinal gray matter and cuneate synapses. Our data also
      demonstrate that earlobe reference recordings are not adequate to measure
      pharmacologic effects on subcortical SEPs.

PMID- 7508857
TI  - Intraoperative recording of parietal SEP can miss hemodynamic infarction during
      carotid endarterectomy: a case study.
AB  - Serial recording of median nerve somatosensory evoked potentials (SEPs) provides
      reliable intraoperative information on critical lowering of brain perfusion which
      compares favorably with other monitoring methods. However, single-channel
      parietal SEP recording may not detect hemodynamic cerebral infarctions affecting
      the pre-rolandic area. Following left carotid endarterectomy for high-grade
      symptomatic stenosis in a 66-year-old male, predominantly motor hemiparesis and
      aphasia were detected which were largely reversible. Pre- and intraoperative SEPs
      were normal. Postoperative SEPs showed significant interhemispheric amplitude
      differences. Postoperative CT examinations demonstrated hemodynamic watershed
      type infarctions. This rare complication of carotid endarterectomy was not
      detected by intraoperative single-channel parietal SEP monitoring.

PMID- 7508858
TI  - Machine scoring of somatosensory evoked potentials.
AB  - A machine-scoring algorithm was developed for automatic identification and
      measurement of the positive and negative peaks of short-latency somatosensory
      evoked potentials (SEPs). The algorithm enables objective and consistent
      identification and naming of specific components with minimal operator
      involvement, avoiding inaccuracies and variability resulting from differences in
      the criteria used by different operators, or by the same operator at different
      times. The algorithm is based on finite impulse response filtering of wave forms
      from 4 conventional recording channels at a bandpass of 90-240 Hz. The bandpass
      was based on the major lobe in power spectra of multiple records and was verified
      as effective by application to numerous wave forms. Peak identification is based
      on identifying the peak at its optimal channel and verifying its consistency with
      corresponding peaks in the other channels. The machine-scoring algorithm was
      validated on SEPs from 120 subjects. The machine-scored peak latencies obtained
      with this procedure were significantly correlated with their manually measured
      counterparts.

PMID- 7508859
TI  - The rat liver epithelial (RLE) cell nuclear protein database.
AB  - The master two-dimensional computer database of rat liver epithelial (RLE)
      cellular proteins (Wirth et al., Electrophoresis 1991, 12, 931-954) has been
      expanded to include detailed information concerning 1100 nucleoplasmic
      (cytosolic) and 850 particulate associated [35S]methionine labeled as well as 215
      nucleoplasmic and 269 particulate associated [32P]orthophosphate labeled RLE
      nuclear polypeptides, respectively. The RLE nuclear protein database developed
      using the Elsie 5 gel analysis system contains both qualitative and quantitative
      annotations including polypeptide identification number, protein name (if known),
      molecular weight and pI information, quantitation and polypeptide spot shape,
      subcellular location, as well as specific information regarding transformation
      (chemical and spontaneous) and growth-related characteristics. Microsequencing of
      polypeptides directly from two-dimensional (2-D) blotted membranes has recently
      been established in our laboratory and provides a highly efficient and rapid
      means of polypeptide identification in the absence of specific antibodies. At
      present the RLE protein database is still in the developmental stage and is
      continually being updated as additional information is obtained. Nonetheless, it
      is anticipated that knowledge obtained concerning the identification and
      characterization of specific transformation and/or growth regulatory proteins in
      the RLE in vitro cell system will not only have direct application to other
      rodent and human 2-D protein databases currently under development but will also
      complement them.

PMID- 7508860
TI  - Identification of a common hyaluronan binding motif in the hyaluronan binding
      proteins RHAMM, CD44 and link protein.
AB  - We have previously identified two hyaluronan (HA) binding domains in the HA
      receptor, RHAMM, that occur near the carboxyl-terminus of this protein. We show
      here that these two HA binding domains are the only HA binding regions in RHAMM,
      and that they contribute approximately equally to the HA binding ability of this
      receptor. Mutation of domain II using recombinant polypeptides of RHAMM
      demonstrates that K423 and R431, spaced seven amino acids apart, are critical for
      HA binding activity. Domain I contains two sets of two basic amino acids, each
      spaced seven residues apart, and mutation of these basic amino acids reduced
      their binding to HA--Sepharose. These results predict that two basic amino acids
      flanking a seven amino acid stretch [hereafter called B(X7)B] are minimally
      required for HA binding activity. To assess whether this motif predicts HA
      binding in the intact RHAMM protein, we mutated all basic amino acids in domains
      I and II that form part of these motifs using site-directed mutagenesis and
      prepared fusion protein from the mutated cDNA. The altered RHAMM protein did not
      bind HA, confirming that the basic amino acids and their spacing are critical for
      binding. A specific requirement for arginine or lysine residues was identified
      since mutation of K430, R431 and K432 to histidine residues abolished binding.
      Clustering of basic amino acids either within or at either end of the motif
      enhanced HA binding activity while the occurrence of acidic residues between the
      basic amino acids reduced binding. The B(X7)B motif, in which B is either R or K
      and X7 contains no acidic residues and at least one basic amino acid, was found
      in all HA binding proteins molecularly characterized to date. Recombinant
      techniques were used to generate chimeric proteins containing either the B(X7)B
      motifs present in CD44 or link protein, with the amino-terminus of RHAMM (amino
      acids 1-238) that does not bind HA. All chimeric proteins containing the motif
      bound HA in transblot analyses. Site-directed mutations of these motifs in CD44
      sequences abolished HA binding. Collectively, these results predict that the
      motif of B(X7)B as a minimal binding requirement for HA in RHAMM, CD44 and link
      protein, and occurs in all HA binding proteins described to date.

PMID- 7508861
TI  - Mutational analysis of the [4Fe-4S]-cluster converting iron regulatory factor
      from its RNA-binding form to cytoplasmic aconitase.
AB  - The control of cellular iron homeostasis involves the coordinate post
      transcriptional regulation of ferritin mRNA translation and transferring receptor
      mRNA stability. These regulatory events are mediated by a soluble cytoplasmic
      protein, iron regulatory factor (IRF), which binds specifically to mRNA hairpin
      structures, termed iron-responsive elements (IREs), in the respective mRNAs. IRF
      is modulated by variations of cellular iron levels and exists as either an apo
      protein or a [4Fe-4S]-cluster protein. The two conformations show distinct,
      mutually exclusive functions. High-affinity IRE binding is observed with the apo
      form induced by iron deprivation, but is lost under high iron conditions when IRF
      is converted to the [4Fe-4S]-cluster form which shows cytoplasmic aconitase
      activity. Moreover, IRE binding is inactivated by the sulfhydryl-oxidizing agent
      diamide and fully activated in vitro by 2% 2-mercapto-ethanol, whereas alkylation
      of IRF inhibits IRE binding. In the present study, we analyzed each of the above
      features using site-directed mutants of recombinant human IRF. The results
      support the bifunctional nature of IRF. We conclude that cysteines 437, 503 and
      506 anchor the [4Fe-4S]-cluster, and are essential to the aconitase activity.
      Mutagenesis changing any of the cysteines to serine leads to constitutive RNA
      binding in 0.02% 2-mercaptoethanol. Cysteine 437 is particularly critical to the
      RNA-protein interaction. The spontaneous or diamide-induced formation of
      disulfide bonds between cysteines 437 and 503 or 437 and 506, in apo-IRF, as well
      as its alkylation by N-ethylmaleimide, inhibit binding to the IRE.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7508862
TI  - Antibody fragments from a 'single pot' phage display library as immunochemical
      reagents.
AB  - The display of repertoires of antibody fragments on the surface of filamentous
      bacteriophage offers a new way of making antibodies with predefined binding
      specificities. Here we explored the use of this technology to make immunochemical
      reagents to a range of antigens by selection from a repertoire of > 10(8) clones
      made in vitro from human V gene segments. From the same 'single pot' repertoire,
      phage were isolated with binding activities to each of 18 antigens, including the
      intracellular proteins p53, elongation factor EF-1 alpha, immunoglobulin binding
      protein, rhombotin-2 oncogene protein and sex determining region Y protein. Both
      phage and scFv fragments secreted from infected bacteria were used as monoclonal
      and polyclonal reagents in Western blots. Furthermore the monoclonal reagents
      were used for epitope mapping (a new epitope of p53 was identified) and for
      staining of cells. This shows that antibody reagents for research can be readily
      derived from 'single pot' phage display libraries.

PMID- 7508863
TI  - Evidence of selection for protein introns in the recAs of pathogenic
      mycobacteria.
AB  - Protein introns are recently discovered genetic elements whose intervening
      sequences are removed from a precursor protein by an unusual protein splicing
      reaction. This involves the excision of a central spacer molecule, the protein
      intron, and the religation of the amino- and carboxy-terminal fragments of the
      precursor. The recA gene of Mycobacterium tuberculosis contains one such element
      and we now show that the other major mycobacterial pathogen, Mycobacterium
      leprae, also possesses a protein intron in its recA, although other mycobacterial
      recA genes do not. However, these two protein introns are different in size,
      sequence and location of insertion of their coding sequences into the recAs of M.
      tuberculosis and M. leprae, indicating that acquisition of the protein introns
      has occurred independently in the two species, and thus suggesting that there has
      been selection for splicing in the maturation of RecA in the pathogenic
      mycobacteria. The M. leprae protein intron provides an example of conditional
      protein splicing, splicing occurring in M. leprae itself but not when expressed
      in Escherichia coli, unlike most previously described protein introns. These
      observations suggest that protein introns may perform a function for their host,
      rather than being just selfish elements.

PMID- 7508866
TI  - RT-PCR cloning of Rab3 isoforms expressed in peritoneal mast cells.
AB  - Rab proteins are ras-like low molecular mass GTP-binding proteins, which are
      postulated to act as specific regulators of membrane trafficking in exocytosis
      and endocytosis. We have previously shown that synthetic peptides, corresponding
      to the effector domain of Rab3 proteins, stimulate a complete exocytotic response
      in mast cells. We have used a PCR-cloning strategy to investigate the presence of
      mRNA encoding Rab3 in mast cells. RNA based PCR was then performed on mast cell
      RNA using degenerate oligonucleotide primers based on two conserved sequences
      among Rab3 proteins. However, no PCR products were obtained, even for proteins
      known to be expressed in high copy numbers in mast cells (beta-actin and Fc
      receptor). We have found that the problem resides in the presence of mast cell
      secretory granule derived heparin, that copurifies with the RNA; heparin has been
      shown to inhibit the activity of reverse transcriptase and Taq polymerase in PCR.
      After treating the RNA (obtained from about 500 mast cells) with heparinase,
      several PCR products of varying size were obtained using primers specific for
      Rab3 proteins. These products were cloned and sequenced. We have found clones
      containing sequences that had a 100% homology at the deduced amino acid level to
      a portion of Rab3B and Rab3D (amino acids 16 to 83).

PMID- 7508865
TI  - Phospholipase A2 enhances [3H]AMPA binding to a putative homomeric GluR-B
      receptor in the rat spinal cord.
AB  - [3H]AMPA and [3H]kainate binding to rat spinal cord was localised most densely in
      the substantia gelatinosa of the dorsal horn. Phospholipase A2 elicited a dose
      dependent increase in specific [3H]AMPA binding but not in [3H]kainate binding.
      The enhancement of [3H]AMPA binding was blocked by bromophenacyl bromide and at 0
      degree C and was not mimicked by arachidonic acid. Since GluR-B is the only AMPA
      receptor subunit detectable in the rat spinal cord, and recombinant homomeric
      GluR-B assemblies do not bind [3H]kainate, these results suggest phospholipase A2
      may modulate [3H]AMPA binding to putative homomeric GluR-B receptors.

PMID- 7508864
TI  - Anti-inflammatory effects of glucocorticoids and cyclosporin A on human
      basophils.
AB  - Pro-inflammatory and vasoactive mediators released from human basophils and mast
      cells play a role in several inflammatory and immune disorders. It was recently
      demonstrated that cyclosporin A (CsA) exerts anti-inflammatory effects by
      inhibiting the release of preformed and de novo synthesized mediators from human
      basophils. This study compared the effects of pharmacological concentrations of
      deflazacort (DFZ) and prednisolone (PRED) on the anti-IgE-mediated release of
      preformed (histamine) and de novo synthesized (leukotriene C4: [LTC4]) mediators
      from basophils. Basophils were cultured for 18 hours in the presence of
      pharmacological concentrations of DFZ (10(-8) to 3 x 10(-6) M). DFZ inhibited the
      anti-IgE-mediated release of histamine and LTC4 from basophils in a concentration
      dependent manner (6-40%), and had a similar efficacy and potency to PRED. The
      effect of DFZ (10(-8) to 10(-7) M) in combination with CsA on the immunological
      release of histamine and LTC4 from basophils was also evaluated. An 18-hour
      incubation of basophils with DFZ (10(-8) M) followed by a short (15-minute)
      incubation with CsA (30 ng/ml) resulted in an additive inhibition of the release
      of histamine and LTC4. The additive anti-inflammatory effect of these drugs makes
      them interesting candidates for future controlled clinical trials in inflammatory
      diseases in which basophil-derived mediators play a relevant role.

PMID- 7508867
TI  - Polychlorinated biphenyls modulate protooncogene expression in Chang liver cells.
AB  - n Chang liver cells we studied the influence of polychlorinated biphenyls (PCB)
      on the expression of different protooncogenes. In cells incubated with medium
      supplemented with PCB we observed an early effect after 3 h on c-erbA and c-erbB
      RNA level. This reduction of RNA was due to a delayed transcriptional activation
      of the genes. The PCB congener 3,3',4,4',5-pentachlorobiphenyl (5-CB) in a 1,000
      fold lower concentration influenced protooncogene expression in the same manner.
      In contrast c-raf RNA level increased transiently after 24 h. The fact that
      persistent chemicals like PCB interfere with protooncogene expression is
      particularly interesting in view of their tumor promoting activity.

PMID- 7508868
TI  - Inhibition of the Ca(2+)-activated K(+)-channel by sapecin B, an insect
      antibacterial protein.
AB  - Sapecin is an antibacterial protein of the flesh fly and sapecin B is its
      homologue structurally similar to charybdotoxin of scorpion venom, which is known
      to be a K+ channel inhibitor. We found that, like charybdotoxin, sapecin B
      inhibits part of the voltage pulse-induced K+ currents of rat cerebellar Purkinje
      cells. We suggest that this effect is due to inhibition of the Ca(+)-activated K+
      channel. Probably, sapecin B is a naturally occurring K+ channel inhibitor as
      well as an antibacterial protein.

PMID- 7508869
TI  - Sequence-specific cleavage of RNA by a hybrid ribonuclease H.
AB  - Site-specific cleavage of the 22-, 132- and 534-base RNAs by the DNA/protein
      hybrid RNase H were examined. The 22-base RNA was chemically synthesized, and 132
      and 534-base RNAs were prepared by run-off transcription. The hybrid enzyme
      cleaves these RNAs, which contain a single target sequence, primarily at the
      unique phosphodiester bond within the target sequence. The hybrid enzyme performs
      multiple turnovers, and at a substrate/enzyme ratio of 10:1 the RNAs are almost
      completely cleaved by the hybrid enzyme at 37 degrees C within 1 h. We propose
      that hybrid RNase H molecules with various oligodeoxyribonucleotides function as
      RNA restriction enzymes and are useful for structural and functional studies of
      RNA.

PMID- 7508870
TI  - Inhibition of epidermal growth factor-dependent protein tyrosine phosphorylation
      by phorbol myristate acetate is mediated by protein tyrosine phosphatase
      activity.
AB  - Incubation of HER14 cells with phorbol myristate acetate (PMA) decreases
      epidermal growth factor (EGF)-dependent protein tyrosine phosphorylation, except
      for a 40-kDa MAP kinase II-like protein, whose tyrosine phosphorylation is
      further enhanced. The inhibitory effect of PMA on EGF-dependent protein tyrosine
      phosphorylation is reversed if cell are pre-incubated with a combination of
      Na3VO4 and NaF, two known inhibitors of protein tyrosine phosphatase activity.
      Protein tyrosine phosphatase activity of cell homogenate was measured on
      immunopurified EGF receptor, and was found to be enhanced in PMA-treated cells.
      These data suggest that the inhibitory effect of PMA on EGF-dependent protein
      tyrosine phosphorylation in HER14 cells may be mediated by protein tyrosine
      phosphatase activity.

PMID- 7508871
TI  - Induction of apoptosis in murine ACTH-secreting pituitary adenoma cells by
      bromocriptine.
AB  - Bromocriptine, a dopamine agonist, is now an accepted primary therapeutic agent
      for patients with prolactinomas and other pituitary adenomas. In this study, we
      demonstrated that bromocriptine inhibited the proliferation of murine ACTH
      secreting pituitary adenoma (AtT-20) cells. In addition, the antitumor activity
      of bromocriptine was inhibited both by actinomycin D and cycloheximide,
      suggesting that it was dependent on new RNA and protein synthesis. Interestingly,
      the results of DNA fragmentation assays and cell cycle analysis clearly
      demonstrated that bromocriptine induced apoptosis in AtT-20 cells.

PMID- 7508872
TI  - Tenascin-C in rat lung: distribution, ontogeny and role in branching
      morphogenesis.
AB  - Extracellular matrix is important to organogenesis and may function by modifying
      cellular adhesion, motility, proliferation, and differentiation. Tenascin-C (TN
      C) is a matrix molecule reported to bind some cell lines and to inhibit adhesion
      of some cell types to fibronectin. This report describes the ontogeny and
      possible functions of TN-C expression in fetal and newborn rat lung. There was a
      moderate concentration of TN-C protein at the epithelial-mesenchymal interface
      during fetal lung development in the period of branching morphogenesis. There was
      a remarkable accumulation of TN-C during the first postnatal week when
      alveolarization peaked, followed by a decline to barely detectable levels after
      the third postnatal week when alveolarization was essentially completed. Loss of
      TN-C protein followed quickly the loss of TN-C mRNA, suggesting a rapid turnover
      of TN-C in the extracellular matrix. By light microscopy, immunoreactive TN-C was
      present in early postnatal lung at the epithelial-mesenchymal interface and was
      distributed throughout lung mesenchyme. Electron microscopic immunocytochemistry
      showed TN-C was not a part of the basal lamina and that its lung localization was
      punctate and different from the uniform distribution of laminin. Antiserum to TN
      C significantly inhibited branching morphogenesis of fetal lung explants but did
      not block their growth. Three bacterially expressed segments of TN-C comprising
      different fibronectin type III domains inhibited branching morphogenesis as
      effectively as did antiserum, but an expression protein of the carboxyterminal
      fibrinogen-like segment had no effect. We conclude that TN-C is expressed in a
      spatio-temporal pattern consistent with a role in lung development and our in
      vitro studies indicated a functional role for TN-C during lung branching
      morphogenesis.

PMID- 7508873
TI  - Vanadate augments insulin-stimulated insulin receptor kinase activity and
      prolongs insulin action in rat adipocytes. Evidence for transduction of amplitude
      of signaling into duration of response.
AB  - Vanadate, a protein tyrosine phosphatase inhibitor, preserves insulin-stimulated
      lipogenesis after removal of insulin. To investigate the mechanism of this action
      of vanadate, lipogenesis was studied in isolated rat adipocytes exposed to
      vanadate for 60 min followed by insulin for 15 min at 37 degrees C. Vanadate (10
      50 microM) prolonged insulin-stimulated lipogenesis. The half-time (t1/2) of the
      decay in insulin (0.34 nM)-stimulated lipogenesis after removal of insulin by
      washing in pH 7.0 followed by pH 7.6 buffer was 21 min in the absence and 59 min
      in the presence of vanadate. During these conditions, vanadate did not alter
      insulin binding nor the removal of insulin by the series of washes. In contrast
      to lipogenesis, the t1/2 of the decay in insulin receptor tyrosine kinase (IRK)
      activity, assayed with the artificial substrate Poly[Glu:Tyr] (4:1), was not
      significantly prolonged by vanadate (6 vs. 6.8 min). However, insulin-stimulated
      IRK activity was markedly augmented by vanadate to 319 +/- 19% of insulin alone,
      associated with a similar augmentation of phosphotyrosine incorporation into the
      insulin receptor beta-subunit determined by Western blotting with
      antiphosphotyrosine antibodies. To determine the relationship between
      prolongation of lipogenesis and the increase in IRK, adipocytes were exposed to
      17.2 nM insulin to activate the IRK to the same extent as insulin (0.34 nM) plus
      vanadate (maximum activation). During these two conditions, the decay of
      lipogenesis was similar and after stimulation with 17.2 nM insulin was not
      prolonged by vanadate. We conclude that vanadate prolongs insulin action at
      insulin concentrations that do not maximally activate the IRK by augmenting IRK
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508874
TI  - Search for a third susceptibility gene for maturity-onset diabetes of the young.
      Studies with eleven candidate genes.
AB  - Maturity-onset diabetes of the young (MODY) is a model for genetic studies of non
      insulin-dependent diabetes mellitus. We have identified 15 MODY families in which
      diabetes is not the result of mutations in the glucokinase gene. This cohort of
      families will be useful for identifying other diabetes-susceptibility genes. Nine
      other candidate genes potentially implicated in insulin secretion or insulin
      action have been tested for linkage with MODY in these families, including
      glucokinase regulatory protein, hexokinase II, insulin receptor substrate 1,
      fatty acid-binding protein 2, glucagon-like peptide-1 receptor, apolipoprotein C
      II, glycogen synthase, adenosine deaminase (a marker for the MODY gene on
      chromosome 20), and phosphoenolpyruvate carboxykinase. None of these loci showed
      evidence for linkage with MODY, implying that mutations in these genes do not
      make a major genetic contribution to the development of MODY. In addition to
      these linkage analyses, one or two affected subjects from each family were
      screened for the presence of the A to G mutation at nucleotide 3,243 of the
      mitochondrial tRNA(Leu(UUR)) gene. This mutation was not found in any of these
      subjects. Finally, we report the localization of the gene encoding the regulatory
      protein of glucokinase to chromosome 2, band p22.3 and the identification of a
      restriction fragment length polymorphism at this locus.

PMID- 7508875
TI  - Troglitazone prevents glucose-induced insulin resistance of insulin receptor in
      rat-1 fibroblasts.
AB  - Troglitazone (CS045), a compound belonging to the thiazolidine diones, is being
      tested as a new oral antidiabetic agent. Evidence exists from animal studies and
      clinical trials with non-insulin-dependent diabetes mellitus patients that
      Troglitazone might reduce insulin resistance. The molecular mechanism of this
      effect is not understood. In this study, we investigated whether Troglitazone
      might interfere with the mechanism of glucose-induced insulin resistance. Several
      studies indicate that hyperglycemia reduces the kinase activity of the insulin
      receptor in different cell types. This effect is paralleled by translocation of
      several protein kinase C (PKC) isoforms, and it can be prevented by PKC
      inhibitors, which suggests that glucose-induced receptor desensitization is
      mediated by activation of PKC. We studied the effect of hyperglycemia on the
      insulin receptor kinase activity and its modulation by Troglitazone in rat-1
      fibroblasts that stably overexpress the human insulin receptor. Before
      stimulation with insulin (10(-7) M), cells were acutely exposed to hyperglycemic
      conditions in the absence or presence of Troglitazone (0.01-2 micrograms/ml). The
      insulin receptor was solubilized from a plasma membrane fraction or whole cell
      lysates, and proteins were separated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and immunoblotted against antiphosphotyrosine and anti-insulin
      receptor beta-subunit (CT 104) antibodies. Acute hyperglycemia (25 mM glucose)
      induced a significant inhibition of the insulin receptor kinase (IRK) activity
      within 30 min (inhibition to 30 +/- 12.5% of maximal insulin-stimulated beta
      subunit phosphorylation, n = 9, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508876
TI  - Tissue distribution of TAG-72 in malignant mixed mullerian tumors of the uterus.
AB  - Malignant mixed mullerian tumors are the most frequent sarcomas arising from the
      uterus. Since these tumors are traditionally associated with a poor prognosis,
      tumor-associated antigens may be useful in the evaluation and follow-up of
      affected patients. The purpose of this study was to determine the frequency and
      tissue distribution of TAG-72, an antigen frequently expressed in endometrial
      carcinomas, and to compare it to CA 125 and CA 19-9 expression in malignant mixed
      mullerian tumors of the uterus. Consecutive, paraffin-embedded sections from 35
      tumors were immunohistochemically evaluated using primary antibodies directed
      against the tumor-associated antigens. These antigens were demonstrated in the
      neoplastic glandular epithelium and not in the sarcomatous portion of the tumor.
      The degree of antigen expression was unrelated to the nature of the sarcomatous
      element present (homologous vs heterologous). Positive staining (> or = 5% of the
      glandular epithelium) for TAG-72 was present in 66% of the tumors; another 6% of
      the tumors contained focal staining (< 5% of the glandular epithelium) for TAG
      72. Although cytoplasmic and intraluminal staining were present, cell surface
      staining was the most prominent feature of TAG-72 expression. Tumors were more
      likely to be positive for TAG-72 than either CA 125 (P = 0.046) or CA 19.9 (P =
      0.004). The extent of TAG-72 expression was unrelated to the extent of disease
      (intrauterine vs extrauterine) and overall patient survival. However, antigen
      expression was correlated with the differentiation of the glandular component
      present.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508877
TI  - Overexpression of p53 is not a feature of benign and early-stage borderline
      epithelial ovarian tumors.
AB  - Since overexpression of mutant p53 protein is a common feature of invasive
      epithelial ovarian cancers, we investigated whether overexpression of the p53
      tumor suppressor gene product occurs in benign and borderline epithelial ovarian
      tumors. Immunohistochemical staining for p53 was performed in frozen samples of
      17 benign tumors and in 49 borderline tumors (4 frozen, 45 paraffin embedded).
      Overexpression of p53 was observed in 0/17 (0%) benign ovarian tumors and 2/49
      (4%) borderline tumors. Overexpression of p53 in borderline tumors was only seen
      in advanced stage cases; overexpression was seen in 2/8 (25%) stage III cases,
      but not in any of 41 stage I/II cases. In conclusion, overexpression of p53 is
      not a feature of benign epithelial ovarian tumors or early-stage borderline
      ovarian tumors. Similar to invasive epithelial ovarian cancers, however, a
      fraction of metastatic borderline tumors also overexpress p53.

PMID- 7508878
TI  - Extremely high levels of CA19-9 and CA125 antigen in benign mucinous ovarian
      cystadenoma.
AB  - A Japanese woman had a mucinous cystadenoma of the left ovary associated with
      very high serum levels of CA19-9 (3170 u/ml) and CA125 (1705 u/ml). Such high
      levels of both antigens have not been reported previously in patients with benign
      ovarian mucinous cystadenoma. Immunostaining demonstrated CA19-9 and CA125 in the
      tumor, and different patterns of expression were noted depending on the
      differentiation of the epithelium. The postoperative tumor marker profile
      suggested that no residual tumor was left after the operation.

PMID- 7508879
TI  - [Effects of cyclosporin A on experimental nephritis in rats (2): Cyclosporin A
      suppresses the development of accelerated passive Heymann nephritis].
AB  - We investigated the effects of cyclosporin A (CyA) on accelerated passive Heymann
      nephritis, an experimental model of membranous nephropathy, that is characterized
      by immune complex deposition on the glomerular basement membrane. The nephritis
      was induced in rats by injection of antiserum against the antigen located in the
      renal tubular brush border membrane and sensitization with rabbit gamma-globulin.
      CyA was administered p.o. at the dose of 2.5, 10 or 20 mg/kg/day for 40 days
      after the injection of the antiserum. The administration of CyA resulted in
      marked suppression of proteinuria and hypercholesterolemia in the nephritic rats.
      In light microscopy, nephritic control rats showed thickening of the glomerular
      basement membrane and spike formation in the glomeruli. CyA significantly reduced
      the appearance of the glomerular alteration. The production of antibody was
      dramatically attenuated by CyA administration. However, CyA did not decrease the
      number of circulating white blood cells and platelets below the normal level. In
      conclusion, CyA suppressed the progress of accelerated passive Heymann nephritis
      in a dose-dependent manner. The effect of CyA is likely attributable to the
      powerful depression of antibody production.

PMID- 7508880
TI  - Hyaline globules in ovarian tumours.
AB  - Hyaline eosinophilic globules have so far been described in a restricted variety
      of tumour types. We have noted their presence in a variety of gynaecological
      malignancies, in particular mixed Mullerian tumours and other epithelial ovarian
      tumours. We therefore studied their incidence and distribution in a series of
      malignant, borderline and benign epithelial ovarian tumours, and endometrial and
      endocervical adenocarcinomas. Hyaline eosinophilic globules were found in all 30
      mixed Mullerian tumours from various sites in the female genital tract, 22 of 30
      clear cell carcinomas, seven of 30 serous, two of 30 mucinous, and one of 30
      endometrioid carcinomas examined, and were also seen in metastases from these
      tumours. They were present in only two of 25 borderline serous, one of 25
      borderline mucinous tumours, and in four of 50 benign serous and one of 50 benign
      mucinous tumours. The globules were not found in any of 25 Brenner tumours
      examined, nor in 30 endometrial or 30 endocervical adenocarcinomas. The globules
      were periodic acid-Schiff positive after diastase, stained positively with PTAH,
      and were immunoreactive for alpha-1-antitrypsin. This study therefore
      demonstrates that eosinophilic globules are not specific for any particular
      tumour. However, their frequency in malignant mixed Mullerian tumours suggests
      that this diagnosis should be carefully excluded whenever these globules are
      present in epithelial tumours of the female genital tract.

PMID- 7508881
TI  - Cutaneous meningioma: histochemical, immunohistochemical and ultrastructural
      investigation.

PMID- 7508884
TI  - Spermatocytic seminoma: an immunohistochemical study.
AB  - Spermatocytic seminoma (SS) is an unusual germ cell tumor that behaves in an
      indolent fashion. Because orchiectomy alone in adequate treatment, it is
      important to distinguish SS from classic seminoma and other germ cell tumors.
      Light microscopic distinction usually is possible; however, occasional cases of
      SS exhibit atypical features, including the presence of a lymphoid infiltrate or
      microcystic change, which simulate classic seminoma and yolk sac tumor,
      respectively. Immunohistochemistry might aid in this differential diagnosis, but
      the immunohistochemical profile of SS is not well reported in the literature. We
      examined seven SS cases (six men and one non-human primate) with a panel of 14
      antibodies directed against placental-like alkaline phosphatase (PLAP), keratins
      (CAM 5.2, AE1/AE3), vimentin, human chorionic gonadotropin, alpha-fetoprotein,
      muscle-specific actin, carcinoembryonic antigen, S-100 protein, epithelial
      membrane antigen, desmin, leukocyte-common antigen, neuron-specific enolase, and
      human placental lactogen. A previously unreported finding was the presence of
      focal cytoplasmic staining for low molecular weight cytokeratin (CAM 5.2) in
      three cases. All other antibodies produced essentially negative results,
      including anti-PLAP. The PLAP and neuron-specific enolase negativity of SS are in
      contrast to the positivity of classic seminoma for these markers. A simplified
      panel of antibodies is recommended to assist in the differentiation of SS from
      other forms of germ cell neoplasia.

PMID- 7508883
TI  - Multidirectional differentiation in the normal, hyperplastic, and neoplastic
      human prostate: simultaneous demonstration of cell-specific epithelial markers.
AB  - The prostatic epithelium is composed of three distinct cell populations:
      secretory luminal, basal, and endocrine-paracrine cells. It is currently unknown
      whether these basic epithelial cell types are related in a hierarchical pathway
      of differentiation or are independent and separate entities. In the present study
      we used double-label techniques for cell-specific markers to search for
      multidirectional differentiation in normal, hyperplastic, and neoplastic prostate
      tissue. In normal and hyperplastic conditions subsets of basal cells revealed
      synchronous expression of basal cell-specific cytokeratins and the prostate
      specific antigen, indicating intermediate differentiation between basal and
      secretory luminal cell types. Furthermore, endocrine-paracrine cells of the
      closed type focally showed simultaneous expression of chromogranin A and basal
      cell-specific cytokeratins. These findings highlight the phenotypic plasticity of
      the basal cell layer in the human prostate. In prostatic adenocarcinoma co
      expression of exocrine (prostate-specific antigen) and endocrine (chromogranin A)
      markers was detected frequently in subsets of malignant cells. Conversely, this
      amphicrine phenotype was rarely found in hyperplastic glands. The occurrence of
      multidirectional differentiation within the prostatic endocrine cell system may
      indicate that endocrine-paracine cells derive from pluripotent stem cells of
      endodermal origin. Furthermore, the phenotypic plasticity of basal cells suggests
      that this epithelial compartment houses stem cell populations that give rise to
      all epithelial cell lineages encountered in the normal, hyperplastic, and
      neoplastic human prostate.

PMID- 7508886
TI  - Association of p53 immunoreactivity with high gleason tumor grade in prostatic
      adenocarcinoma.
AB  - To determine whether p53 immunoreactivity correlates with the Gleason tumor grade
      in primary adenocarcinoma of the prostate we analyzed 107 consecutive surgical
      specimens (78 radical prostatectomies and 29 transurethral resections). A
      hematoxylin-eosin-stained slide from a representative block of each tumor was
      examined, and primary and secondary Gleason scores were assigned in each case.
      Additional paraffin sections from the same block were stained
      immunohistochemically for p53 expression using the monoclonal antibody clone DO
      1, a mouse IgG2a directed against a denaturation-resistant epitope of p53. Four
      of 54 (7.4%) low-grade tumors (combined Gleason score of 6 and below) and 11 of
      53 (20.8%) high-grade tumors (combined Gleason score of 7 and above) revealed
      strong nuclear positivity for p53. When evaluated using only the primary Gleason
      score, none of 23 (0%) Gleason grade 2 tumors and 15 of 84 (17.9%) Gleason grade
      3 or higher tumors were positive. These data demonstrate a positive association
      between p53 immunoreactivity and higher Gleason grade tumors (P = .04 for the
      combined score, P = .02 for primary score only). In addition, we noted occasional
      p53-positive nuclei in basal cells of benign glandular acini in regions flanking
      tumor. Focally positive nuclear staining also was demonstrated in basal cells
      from nine of 25 prostate glands exhibiting benign prostatic hyperplasia with no
      tumor. These results suggest that p53 overexpression might be associated with the
      known proliferative capacity of basal cells in benign hyperplastic prostate
      glands, and that mutations of p53 might play a role in the pathogenesis of a
      subset of high-grade prostate adenocarcinomas.

PMID- 7508885
TI  - Expression of the myelomonocytic antigens CD36 and L1 by keratinocytes in
      squamous intraepithelial lesions of the cervix.
AB  - The keratinocytes in squamous intraepithelial lesions (SILs) of the cervix show
      altered expression of a number of molecules involved both in the control of
      growth and differentiation and in cell surface interactions, particularly with
      components of the immune system. We have used tissue biopsies and in vitro model
      systems to investigate the expression in SILs of the molecules CD36 and L1, which
      are predominantly expressed by myelomonocytic cells but which also have
      functional roles in keratinocyte biology. Whereas the L1 protein (defined by the
      monoclonal antibody Mac387) was expressed by suprabasal and superficial cells in
      12 of 12 cases of normal cervix (NCx) and in 14 of 14 cases of low-grade SILs (LG
      SILs), in two of 16 cases of high-grade SILs (HG-SILs) it was entirely absent and
      in the remainder it was restricted to the most superficial layers. When an
      arbitrary grading scale was applied, L1 expression in HG-SILs proved to be
      significantly lower than in LG-SILs (P < .01) or in cases of NCx (P < .01). CD36
      was expressed by superficial cells in four of 12 cases of NCx, in six of 14 LG
      SILs, and none of 16 cases of HG-SILs (when graded, LG-SILs v HG-SILs = P < .05).
      The mechanisms underlying the expression of both molecules were investigated by
      growth in organotypic tissue culture of normal ectocervical epithelium and the
      cervical keratinocyte cell lines W12 (a model for LG-SILs) and CaSki and SiHa
      (models for HG-SILs). L1 was diffusely expressed by NCx cells and the W12 cell
      line, although its expression in the CaSki and SiHa cell lines was much more
      irregular and restricted. CD36 was occasionally present on the surface of
      superficial NCx and W12 cells, but was absent from CaSki and SiHa cells. Neither
      molecule could be induced by treatment of the cells with interferon-gamma. These
      data suggest that the expression of CD36 and L1 by cervical keratinocytes is
      related to their differentiation status rather than representing an effect of
      exogenous factors, such as those released by the immune cell infiltrate
      associated with SILs. CD36 may function as an immunoregulatory molecule on
      cervical keratinocytes in SILs, while L1 is more likely to be involved in the
      intracellular regulation of cell proliferation and maturation.

PMID- 7508882
TI  - An exaltation of experts: concerted efforts in the standardization of
      immunohistochemistry.

PMID- 7508891
TI  - UICC Study Group on basic and clinical cancer research: tumor angiogenesis.
      Meeting held at Woods Hole, MA, September 18-21, 1993.

PMID- 7508888
TI  - Human papillomavirus type 18 E6* mRNA in primary tumors and pelvic lymph nodes of
      Hungarian patients with squamous cervical cancer.
AB  - Seven biopsy specimens from squamous-cell carcinomas of the uterine cervix were
      examined by RT-PCR for human-papilloma-virus(HPV)-specific transcripts. With our
      HPV18-transcription-specific primer pair (5' nts 127-149; 3' nts 587-607), all 7
      were shown to contain one strong viral mRNA signal from the early 6/early 7 open
      reading frames (E6/E7 ORFs). Sequence analysis of the cloned PCR product proved
      that the transcript was generated by splicing out an intron in E6 from
      nucleotides 233 to 416, thereby corresponding to the HPV18 E6* spliced mRNA. Nine
      out of 9 metastatic and 5 of 7 histologically negative lymph nodes from the same
      patients were also found to be positive for the same mRNA transcript. However, 4
      HPV18 unrelated primary tumors and the connected regional pelvic lymph nodes (3
      metastatic, 7 histologically negative) were negative for the HPV18 E6* mRNA.
      Cytokeratin signals indicating tumor cells of epithelial origin were detected in
      7 out of the 9 transcript-positive lymph nodes with histological signs of
      metastasis and in 2 out of the 5 transcript-positive histologically negative
      lymph nodes. This suggests that the dispersion of the epithelial monoclonal tumor
      cells was lymphogenic in origin.

PMID- 7508887
TI  - Functional and phenotypic assessment of neonatal human leucocytes expressing
      natural killer cell-associated antigens.
AB  - A subpopulation of mononuclear leucocytes was prepared from umbilical cord venous
      blood by immunomagnetic depletion of lymphocytes and monocytes using monoclonal
      antibodies to CD2, CD3, CD14 and CD19 antigens, and examined for NK cell
      associated phenotypic and functional properties. The depleted population was
      enriched for the NK markers CD16 (mean 53.6% positive) and CD56 (mean 42.7%
      positive). While there was considerable overlap of these two markers,
      approximately one-third of CD16+ cells were CD56-; in contrast, few CD56+ CD16-
      cells were found. CD16+/CD56+ cells also co-expressed CD7 and CD45RA antigens,
      while a minority weakly expressed CD8. Another marker of adult NK cells, CD57,
      was virtually absent from CD16+/CD56+ cells, as was MHC Class 2. Freshly depleted
      cord cells had virtually absent natural cytotoxicity to K562 targets in a
      chromium release assay, but NK activity could be induced after 18 h exposure to
      recombinant human IL-2, without significant change in phenotype. These findings
      confirm the phenotypic differences and functional defects of NK cells in cord
      blood as compared to adult blood, and identify a subset of cells with unique
      phenotype (CD2- CD3- CD7+ CD16+ CD56- CD57-). The precise relationship of this
      subset of cells to NK lineage remains to be defined.

PMID- 7508889
TI  - The effect of GM-CSF and G-CSF on the growth of human osteosarcoma cells in vitro
      and in vivo.
AB  - The human osteosarcoma cell line, MG63, responds both to GM-CSF and to G-CSF in
      vitro. To assess the significance of these observations to tumor growth in vivo,
      MG63 cells were engineered by retroviral infection to produce human GM-CSF or G
      CSF. These retrovirally infected cells become autostimulatory as measured by
      increased [3H]-thymidine incorporation (3- to 7-fold) and anchorage-independent
      colony formation (7- to 10-fold) as compared with uninfected MG63 cells or cells
      infected with control (neor) retrovirus. The increased proliferation induced by
      exogenous GM-CSF or G-CSF on uninfected MG63 cells in both assays could be
      completely inhibited by anti-GM-CSF or anti-G-CSF antibodies, while the same
      antibodies only partially abrogated proliferation by the growth-factor-producing
      cells. None of 34 nude or SCID mice developed tumors when injected s.c. with
      uninfected or neor-virus-infected cells. In contrast, all 30 mice injected with
      GM-CSF- or G-CSF-producing MG63 cells developed tumors which were G418-resistant
      and factor-producing. Tumor cell DNA showed a polyclonal retroviral integration
      pattern indistinguishable from that in the DNA of cells injected into mice.
      Tumors that formed following injection of a mixture of G418-resistant, GM-CSF
      producing cells and cells infected with virus containing only the hygror gene
      contained hygromycin-resistant cells in the same proportion as was present in the
      original cell mixture. These data indicate that GM-CSF and G-CSF can support the
      growth of an osteosarcoma cell line both in vitro and in vivo whether the factor
      is supplied by autocrine production or from exogenous sources.

PMID- 7508892
TI  - Angiostatic activities of medroxyprogesterone acetate and its analogues.
AB  - The effects of medroxyprogesterone acetate (MPA) (I) and related compounds (II
      VI) upon angiogenesis induced by basic fibroblast growth factor (bFGF) or
      transforming growth factor-alpha (TGF-alpha) were investigated using a rabbit
      corneal system for assay of angiogenesis. Dexamethasone (Dex) was used as a
      positive control. The MPA analogues tested were 6,6'-dehydro-MPA (II), megestrol
      acetate (III), 1-dehydromegestrol acetate (IV), melengestrol acetate (V), and 1
      dehydromelengestrol acetate (VI). The inhibitory activities of these steroids
      using bFGF were in the order: Dex = MPA = (VI) = (V) > (IV) > (III). Steroid (II)
      was inactive. 5 alpha-dihydrotestosterone was weakly active, while estradiol-17
      beta and progesterone were inactive. The angiostatic activity of MPA was
      completely abolished by mefipristone (RU 486) which showed no anti-angiogenic
      activity in this assay. With TGF-alpha, the order of angiostatic activities was
      Dex = (VI) > (IV) > (III) > (V). Steroid (II) was again inactive. Dex, MPA, and
      all the MPA analogues except steroid (II) markedly inhibited the activity of
      plasminogen activator secreted by cultured calf pulmonary artery endothelial
      cells, but did not inhibit growth of these cells. The binding affinities of MPA
      and its analogues to glucocorticoid, progesterone and androgen receptors were
      determined, but were found not to be correlated with their angiostatic
      activities.

PMID- 7508890
TI  - The MHC class-II and CD44 molecules are involved in the induction of tumour
      necrosis factor (TNF) gene expression by human monocytes stimulated with tumour
      cells.
AB  - Tumour necrosis factor alpha (TNF) mRNA is detected in the macrophage infiltrate
      surrounding the tumour, but the cellular/molecular interactions leading to TNF
      gene expression in macrophages are unknown. The in vitro system in which human
      blood monocytes are stimulated with human cancer cells for TNF release was used
      to study such interactions. Monoclonal antibodies (MAbs) against various adhesion
      molecules (LFA-1, LFA-3, ICAM-1, VNR, VLA beta I chain) were unable to block TNF
      production in co-culture of monocytes with a human pancreatic carcinoma (HPC)
      cell line. However, anti-CD44 and anti-HLA-DR MAbs effectively blocked TNF
      release and TNF-mRNA induction in monocytes. Pre-incubation of monocytes with
      anti-HLA-DR and tumour cells with anti-CD44 MAbs had a similar effect. It was
      concluded that CD44 molecules are involved in tumour-monocyte interactions and
      that HLA-DR determinants of monocytes are engaged in signal transduction for TNF
      gene activation. These findings may suggest that certain surface determinants of
      tumour cells act as ligands for MHC class-II molecules and induce TNF production
      in monocytes.

PMID- 7508894
TI  - Cyclic AMP increases the release of parathyroid hormone-related protein from a
      lung-cancer cell line.
AB  - Parathyroid hormone-related protein (PTHrP) plays an important role in the
      pathogenesis of malignant hypercalcemia by stimulating bone resorption and/or
      renal tubular reabsorption of calcium. In cultured cancer cells, its production
      can be influenced by various factors or ions, but the regulation of its
      production is still poorly understood. We investigated the effects of stimulators
      of cAMP synthesis on PTHrP release by a human lung squamous-carcinoma cell line
      (BEN). In superfused cells grown on microcarrier beads, PTHrP production was
      significantly increased after incubation with calcitonin for only 20 min. The
      release of immunoreactive and bioactive PTHrP was increased by incubating the
      cells with forskolin, 3-isobutyl-1-methylxanthine or dibutyryl cAMP even in the
      presence of the protein-synthesis inhibitor cycloheximide for 6 hr. The
      calcitonin-mediated stimulation was not accompanied by concomitant changes in
      PTHrP mRNA. The microfilament-disrupter cytochalasin D was shown to enhance the
      basal and calcitonin-induced production of PTHrP. These results indicate that
      stimulators of cAMP synthesis enhanced PTHrP release by BEN cells.

PMID- 7508893
TI  - TGF-beta receptor regulation mediates the response to exogenous ligand but is
      independent of the degree of cellular differentiation in human oral
      keratinocytes.
AB  - This study examined the expression of TGF-beta cell-surface receptors, the
      response to exogenous TGF-beta 1 and the autocrine production of TGF-beta in
      normal and squamous cell carcinoma-derived human oral keratinocytes with variable
      degrees of cellular differentiation. TGF-beta receptor expression, the response
      to exogenous ligand and the autocrine production of TGF-beta appeared unrelated
      to cellular differentiation. Cells expressed variable proportions of type-I, -II
      and -III TGF-beta receptors. The expression of type-III receptors correlated
      inversely with the expression of type-I receptors, but there was no relationship
      between type-II and either type-I or type-III TGF-beta receptors. Normal cells
      and the majority (7 of 8) of tumour-derived keratinocytes were inhibited by
      exogenous TGF-beta 1 and the degree of inhibition correlated with the expression
      of type-I, but not type-II or type-III, TGF-beta receptors. One tumour-derived
      cell line was refractory to exogenous TGF-beta 1 although it expressed all 3
      receptor types. Endogenous TGF-beta was produced by both normal and tumour
      derived keratinocytes and correlated inversely to the expression of type-I, but
      not type-II, TGF-beta receptors. Further, cells that produced more autocrine TGF
      beta had a diminished response to exogenous TGF-beta 1. The data indicate a
      complex interaction between the expression of TGF-beta cell-surface receptors,
      endogenous ligand production and the cellular response to exogenous TGF-beta 1.

PMID- 7508896
TI  - A repertoire of monoclonal antibodies reveals extensive epitope heterogeneity in
      CEA purified from neoplasms originating from different organs.
AB  - The heterogeneity of carcinoembryonic antigen (CEA) from 5 individual hepatic
      metastases of tumours originating in different organs (1 colon, 1 stomach and 3
      breast adenocarcinomas) was analyzed with a repertoire of 56 alpha CEA murine
      MAbs. In each tumour preparation, the MAbs disclosed 2 distinct molecular species
      displaying remarkable variability in their apparent molecular weights (e.g. 130
      170 kDa for the fast-migrating CEA variant and 180-260 kDa for the slowly
      migrating one). After chemical deglycosylation this heterogeneity was abolished
      and 2 main proteins of 84 and 64 kDa were generated; the difference in their
      molecular weights could not be accounted for by differential glycosylation.
      Although 3 of the analyzed preparations were derived from individual
      adenocarcinomas of the breast, the glycosylated molecules differed considerably
      from one another, in their relative molecular mass. The MAbs used showed
      essentially 3 different recognition patterns according to their reactivity either
      with both CEA molecular weight variants, or just with the higher or the lower
      one. In a quantitative comparison of the immunoprecipitation yields of the MAbs
      with CEA, considerable immunological variability (ranging up to 26-fold), as well
      as preferential expression of CEA epitopes, could be demonstrated among the 5
      different preparations. Here again no uniform epitope presentation could be
      observed among the 3 breast tumours thus far tested. Comparison of the
      precipitation yields with the glycosylated and deglycosylated CEA species
      revealed that, whereas the CEA antigenic heterogeneity remained in some cases
      unchanged, most of the MAbs exhibited, in carbohydrate-free CEA, the appearance
      of a new heterogeneity.

PMID- 7508895
TI  - Inhibition of gastrin-induced proliferation of AR4-2J cells by calcium channel
      antagonists.
AB  - The exact intracellular mechanisms by which gastrin enhances the proliferation of
      AR4-2J cells, a tumor pancreatic acinar cell line, are not precisely known.
      Calcium has long been considered as an intracellular signal involved in growth
      regulatory control of many cell types. Moreover, Ca++ channel blockers show
      growth-suppressing effects in most proliferating cells. In the present study, we
      analyzed the role of nifedipine, a voltage-dependent Ca++ channel antagonist, on
      AR4-2J cells which possess well-defined voltage-dependent Ca++ channels. The
      results showed that 10 nM gastrin induced a transient rise in intracellular
      calcium (Ca++)i followed by a sustained phase which was dependent upon a Ca++
      influx operating through nifedipine-dependent and -independent Ca++ channels.
      Both influxes are necessary for reloading the agonist-sensitive Cai++ pools. In
      parallel, we demonstrated that nifedipine at doses of 1 microM and 3 microM
      preferentially blocked the increase in cell number elicited by 10 nM gastrin and
      0.1 microM Bay K 8644, a Ca++ channel agonist, suggesting that voltage-sensitive
      Ca++ channel activity was required for gastrin-stimulated mitogenesis. Moreover,
      nifedipine had no effect on the proliferation of AR4-2J cells growing in serum
      free medium, indicating that this drug did not simply exert a toxic effect.
      Therefore, Ca++ influx through voltage-dependent Ca++ channels might be an
      important initial step representing a component of a synergistic cooperation
      between different signal transduction pathways involved in gastrin-regulated
      growth.

PMID- 7508897
TI  - A fetal rat urogenital sinus mesenchymal cell line (rUGM): accelerated growth and
      conferral of androgen-induced growth responsiveness upon a human bladder cancer
      epithelial cell line in vivo.
AB  - A cell-cell interaction model was developed to examine the intercellular
      communication between mesenchymal and epithelial cells in vivo, and to define the
      role of androgen and paracrine growth factors in promoting growth and
      differentiation of the target epithelial cells. Using this model system, we have
      demonstrated that, in the presence of androgenic steroids, a fetal urogenital
      sinus mesenchymal cell line exhibited androgen-induced growth responses which
      resulted in an induction of growth of a non-androgen target epithelial cell line
      derived from human urinary bladder. Our results show that: (1) a rat fetal
      urogenital sinus mesenchyme-derived cell line (rUGM) accelerated growth and
      conferred androgen-induced growth responsiveness upon a non-androgen target cell
      line, WH, derived from a human bladder transitional-cell carcinoma (TCC); this
      induction of epithelial tumor growth in vivo occurred in a fibroblast-specific
      manner; (2) live fetal rUGM cells are required to promote WH tumor growth in
      vivo, which suggests that continuous production of factors that may serve as
      mediators for paracrine/autocrine pathways are responsible for androgen
      stimulation of WH tumor growth in vivo; and (3) although WH tumor growth,
      mediated by the presence of rUGM cells, was markedly accelerated by the presence
      of androgen in vivo, androgen and rUGM cells failed to promote the expression of
      a human prostate-specific antigen (PSA) by WH tumors in vivo. Our results
      emphasize the importance of organ-specific fibroblasts that promote tumor growth
      and mediate androgen-induced growth responses; the accelerated growth of the
      bladder epithelium was not accompanied by the expression of PSA, a known
      differentiated gene product produced by human prostatic epithelial cells. This
      report also discusses the potential significance of mesenchymal-epithelial
      cellular interaction which mediates androgen action and may play an important
      role by influencing human prostate tumor growth, progression and differentiation.

PMID- 7508898
TI  - Modulation of the activity and assessment of the receptor selectivity in a series
      of new RGD-containing peptides.
AB  - We have investigated the structure-activity relationship of a series of new
      synthetic RGD analogs and their potential use as specific platelet aggregation
      inhibitors. Twelve short linear peptides showed high potency to inhibit
      aggregation in ADP-stimulated dog platelets. In order to assess the selectivity
      of these analogs towards platelet integrin GPIIb-IIIa, a new cell adhesion
      inhibition system was devised which was able to discriminate between the two
      closely related beta 3-integrins of the vasculature, GPIIb-IIIa (alpha IIb beta
      3), present in platelets, and the vitronectin receptor (alpha v beta 3),
      expressed in endothelial cells and platelets. As reported for other peptides by
      Scarborough et al. (1993, J. Biol. Chem. 268, 1066), the analogs containing
      lysine instead of arginine in position 1 showed increased selectivity towards
      GPIIb-IIIa. One of them, in which the piperidine carboxylic group was attached to
      the N-terminus of KGDW, not only strongly inhibited platelet aggregation, but
      also selectively abolished cell adhesion mediated by GPIIb-IIIa without effect on
      the vitronectin receptor.

PMID- 7508899
TI  - Peptides from multiple regions of the lectin domain of P-selectin inhibiting
      neutrophil adhesion.
AB  - The selectins are a family of three structurally related glycoproteins that are
      integral components of leukocyte adhesion to the vascular endothelium. Their
      involvement in the recruitment and extravasation of neutrophils is critical in
      mounting an inflammatory reaction. The carbohydrate nature of the selectin
      ligands suggests that the binding regions of the selectins are contained within
      the lectin-like domains of the selectins. The synthesis and evaluation for
      inhibition of selectin binding of overlapping peptides of the lectin and adjacent
      EGF-like domains of P-selectin have been used to identify small peptides that
      completely inhibit P-selectin-dependent neutrophil adhesion. These peptides span
      a region of more than 100 amino acids and may define the carbohydrate recognition
      domain of P-selectin.

PMID- 7508901
TI  - Rodriguez vs. Attorney General of Canada (petitioners testimony).

PMID- 7508900
TI  - [61-year-old patient with hemorrhagic diathesis and fatigue].

PMID- 7508902
TI  - Anti-T11.1 and -T11.2 monoclonal antibodies play a different role in CD2-mediated
      signal transduction.
AB  - We comparatively evaluated (Ca2+)i mobilization after triggering with a
      stimulatory pair of CD2 (CD2.9, anti-T11.1 + CD2.1, anti-T11.2) or CD3 mAbs in
      the differentiated T-cell line Jurkat, using INDO-1 labeling and cytofluorimetry.
      The results obtained showed different (Ca2+)i mobilization kinetics following CD2
      or CD3 stimulation (the former being slower than the latter), not due to
      different association kinetics of mAbs. In a nonreciprocal manner, however,
      preliminary interaction with CD2.1 (anti-T11.2) followed by CD2.9 (anti-T11.1)
      induces a rapid (Ca2+)i rise, similar to CD3 stimulation, as shown by
      preincubation experiments. There is no interference between CD2.9 and CD2.1 mAb
      binding. CD2.1 mAb by itself is unable to induce (Ca2+)i mobilization; in
      addition, preincubation with CD2.1 mAb did not modify the CD2, CD3, CD45, or CD28
      immunoprecipitation patterns. Triggering of the epitope recognized by CD2.1 mAb
      may favor, possibly via conformational changes of CD2 molecule or (Ca2+)i
      unrelated metabolic effect(s), optimal signal transduction.

PMID- 7508903
TI  - Binding characteristics of (-)-(R)-2-aminomethylpyrrolidine(1,1
      cyclobutanedicarboxylato)-2-platin um(II) to DNA, RNA and protein molecules in
      HeLa cells and its lethal effect: comparison with cis- and trans
      diamminedichloroplatinums(II).
AB  - HeLa S-3 cells were treated with 195mPt-radiolabeled (-)-(R)-2
      aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)-2-platinum(II)
      (DWA2114R) under various conditions, and the relationship between the lethal
      effect of the agent and the number of platinum (Pt) atoms binding to DNA, RNA and
      proteins was examined. The values of mean lethal concentration for the cells
      treated with DWA2114 at 37 degrees C for 1, 2 and 3 h were 137.3, 75.10 and 51.17
      microM, respectively. Cells were treated identically and the numbers of Pt atoms
      combined with DNA, RNA and protein molecules were determined after fractionation
      of the cells. In this way, the D0 values (D0, dose that would give an average of
      one lethal event per member of the population), expressed as the drug
      concentration, were substituted for the number of Pt atoms combined with each
      fraction. The target volumes, the efficacy of Pt atom to kill cells expressed as
      the reciprocals of the D0 values, were then calculated for each fraction. Our
      findings suggested that DNA was the primary target molecule for cell killing by
      DWA2114R. The target volumes for DNA were 3.36 x 10(4), 4.00 x 10(4) and 4.10 x
      10(4) nucleotides for 1-, 2- and 3-h treated cells, respectively. The cell
      killing effects of DWA2114R were lower than those of cis
      diamminedichloroplatinum(II) (CDDP) by factors of 1.54, 1.42 and 2.51 for 1-, 2-
      and 3-h treatments at 37 degrees C, respectively, in terms of the target volume,
      while those in terms of the mean lethal dose (D0) were 14.8, 11.2 and 16.0,
      respectively. The efficacy of DWA2114R in killing the cells was 2.6 times greater
      than that of CDDP in the 3-h treatment at 0 degrees C.

PMID- 7508905
TI  - A glycoprotein secreted by lung cancer cells is present in human serum as an
      immunoglobulin-binding protein.
AB  - The 6B3-Ag recognized by a monoclonal antibody 6B3 to human large cell lung
      carcinoma cell line (HLC-2) is a high-molecular-weight glycoprotein of 1,000,000.
      Its serum level is increased in various adenocarcinoma patients. When a patient's
      serum with a high concentration of 6B3.Ag (54 micrograms/ml) or concentrated
      6B3.Ag from normal human serum was analyzed by immunoelectrophoresis, 6B3.Ag
      showed a long bimodal precipitin line extending from the per-beta to beta
      globulin region. However, the precipitin line of 6B3.Ag in the HLC-2 culture
      medium was formed only in the pre-beta globulin region. The 6B3.Ag was purified
      from pooled patients' serum by salting out, precipitation by acidification at pH
      4.5 and Sepharose 4B and immunoaffinity chromatographies. Western blotting
      indicated that the 6B3.Ag from human serum contained IgG and/or IgM. The 6B3.Ag
      from human serum showed a dose-dependent reaction in a sandwich enzyme-linked
      immunosorbent assay with anti-6B3.Ag antibody as a solid-phase antibody and anti
      human IgG or anti-human IgM antibody labeled with alkaline phosphatase. The
      6B3.Ag was concluded to be partly present as a complex with IgG and/or IgM in
      human serum, and this complex showed a precipitin line in the beta globulin
      region on immunoelectrophoresis.

PMID- 7508904
TI  - Abundant but inactive-state gp140proto-trk is expressed in neuroblastomas of
      patients with good prognosis.
AB  - Steady-state levels of gp140proto-trk in cell lines and tumor tissues of
      neuroblastoma were examined by immunoblotting with anti-gp140proto-trk. The level
      of gp140proto-trk varied but showed good correlations with the stage of the tumor
      and the age of the patients at the time of diagnosis. Moreover, patients with
      higher expression of gp140proto-trk clearly had a far better survival rate than
      those with lower expression, suggesting that suppression of gp140proto-trk
      strongly correlates with the malignant conversion of the tumor. However, we found
      that neither autophosphorylation of gp140proto-trk nor tyrosine phosphorylation
      of cellular proteins was elevated in tumors of the higher expression group. These
      results suggest that gp140proto-trk does not actively participate in the process
      of transformation or the suppression of malignant conversion. Rather, the higher
      level of gp140proto-trk may reflect the greater level of differentiation of tumor
      cells.

PMID- 7508906
TI  - Increased activity of insulin-like growth factor-binding protein in human thyroid
      papillary cancer tissue.
AB  - It has been shown that both insulin-like growth factor-I (IGF-I) and IGF-binding
      proteins (IGFBPs) are produced by thyroid cells in culture and that the cells
      respond to IGF-I with increased DNA synthesis, suggesting an autocrine/paracrine
      role of IGF-I in the regulation of thyroid cell growth. We investigated the
      tissue contents of immunoreactive IGF-I (irIGF-I) and IGFBPs in human papillary
      carcinoma and compared them with those of normal thyroid tissue. When irIGF-I was
      measured after separation of the IGFBPs by gel-filtration, its content in
      carcinoma tissue was not different from that in adjacent normal tissue (566 +/-
      58 vs. 424 +/- 75 pg/mg protein, N = 10). Nor was there any difference in the
      abundance of IGF-I mRNA expression determined by slot blot analysis. On the other
      hand, IGFBP activity measured in terms of 125I-IGF-I binding was significantly
      higher in cancer extracts. Western ligand blot analysis of IGFBPs revealed
      several species (24-42 kDa) of IGFBPs. The IGF-I-binding activity of 38-41 kDa
      species (corresponding to IGFBP-3) was not different between extracts of cancer
      tissue and those of normal tissue, whereas that of 28-32 kDa species was
      significantly higher in cancer tissue extracts. Since IGFBPs have been reported
      to modulate cellular responses to IGF-I, the present data suggest that higher
      IGFBP activity in cancer tissue is involved in regulating growth of thyroid
      papillary carcinoma cells.

PMID- 7508909
TI  - Interferon alpha induces rapid tyrosine phosphorylation of the vav proto-oncogene
      product in hematopoietic cells.
AB  - The vav proto-oncogene product (p95vav) is specifically expressed in cells of the
      hematopoietic system, contains one Src homology 2 and two Src homology 3 domains,
      and is a substrate for receptor and non-receptor tyrosine kinases. Immunoblotting
      experiments using an anti-phosphotyrosine monoclonal antibody showed that
      interferon alpha (IFN alpha) induces rapid tyrosine phosphorylation of p95vav
      after binding to its cell surface receptor in the U-266 human myeloma cell line.
      The IFN alpha-induced tyrosine phosphorylation of p95vav was time- and dose
      dependent, confirming the specificity of the process. IFN alpha-dependent
      tyrosine phosphorylation of p95vav was also observed in other hematopoietic cell
      lines of B-cell origin (Daudi), T-cell origin (MOLT-4), and promyelocytic origin
      (HL-60). Immunoprecipitation experiments performed with 32P-labeled U-266 cells
      and phosphoaminoacid analysis of the bands corresponding to p95vav showed that
      p95vav is phosphorylated on serine residues prior to IFN alpha stimulation of the
      cells. After IFN alpha stimulation significant amounts of phosphorylation of
      p95vav on tyrosine residues were detectable. Tyrosine phosphorylation of p95vav
      in U-266 and HL-60 cells was also induced by two other Type I IFNs, IFN beta and
      IFN omega. Altogether these data suggest that the vav proto-oncogene product is a
      substrate for a Type I IFN-regulated tyrosine kinase(s) and may be involved in
      the signal transduction pathway of Type I IFNs in hematopoietic cells.

PMID- 7508908
TI  - Division inhibition gene dicF of Escherichia coli reveals a widespread group of
      prophage sequences in bacterial genomes.
AB  - The genomes of various eubacteria were analyzed by Southern blot hybridization to
      detect sequences related to the segment of the defective lambdoid prophage Kim
      which encodes DicF RNA, an antisense inhibitor of cell division gene ftsZ in
      Escherichia coli K-12. Among the homologous sequences found, one fragment from E.
      coli B, similar to a piece of Rac prophage, and two fragments from Shigella
      flexneri were cloned and sequenced. dicF-like elements similar to transcriptional
      terminators were found in each sequence, but unlike dicF these had no effect on
      division in E. coli K-12. Like dicF, these sequences are flanked by secondary
      structures which form potential sites for RNase III recognition. Coding sequences
      located upstream from the dicF-like feature in E. coli B are related to gene sieB
      of bacteriophage lambda, while sequences downstream of the S. flexneri elements
      are similar to the immunity region of satellite bacteriophage P4. Under
      hybridization conditions in which only strong sequence homologies were detected
      in E. coli B and S. flexneri, the genomes of a large variety of microorganisms,
      including some gram-positive bacteria, hybridized to the dicF probe. Our results
      suggest that dicF and its flanking regions are markers of a widespread family of
      prophage-like elements of different origins.

PMID- 7508907
TI  - Cooperative roles of hepatocyte growth factor and plasminogen activator in
      tubular morphogenesis by human microvascular endothelial cells.
AB  - Epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha)
      stimulated cell migration, chemotaxis, and the expression of tissue-type
      plasminogen activator (t-PA) in human omental microvascular endothelial (HOME)
      cells. Hepatocyte growth factor (HGF) stimulated cell proliferation, but had a
      negligible stimulatory effect on cell migration, the expression of t-PA and tube
      like formation into collagen gel in HOME cells. Basic fibroblast growth factor
      stimulated cell proliferation, cell migration, tubulogenesis and the expression
      of urokinase-type plasminogen activator (u-PA) in bovine aortic endothelial (BAE)
      cells. HOME and BAE cells had both high- and low-affinity receptors for HGF. In
      BAE cells, u-PA activity and tube-like structures in collagen gel were induced in
      the presence of HGF alone. In contrast, in HOME cells, t-PA activity and tube
      like structures were induced in the presence of TGF-alpha alone, but not in the
      presence of HGF alone. However, we observed a marked induction of tube formation
      by HOME cells when both t-PA and HGF were added simultaneously. In the model
      system for tumor angiogenesis, when HOME cells were co-cultured with a renal
      cancer cell line, KPK13, tube-like structures were induced in the presence of
      HGF:KPK13 cells expressed large amounts of t-PA mRNA. Our present study suggested
      that HGF in concert with active t-PA could be angiogenic in HOME cells.

PMID- 7508911
TI  - Binding analysis of amino-terminal and carboxyl-terminal regions of the 39-kDa
      protein to the low density lipoprotein receptor-related protein.
AB  - A 39-kDa protein binds to the low density lipoprotein receptor-related
      protein/alpha 2-macroglobulin receptor (LRP/alpha 2MR) and inhibits the binding
      of ligands to this receptor. We recently reported that inhibition of tissue-type
      plasminogen activator binding to LRP/alpha 2MR is mediated by both amino-terminal
      and carboxyl-terminal regions of the 39-kDa protein, whereas inhibition of alpha
      2-macroglobulin-proteinase binding is mediated only by amino-terminal regions. In
      this report we show that amino-terminal and carboxyl-terminal regions of the 39
      kDa protein bind specifically and with high affinity to LRP/alpha 2MR on rat
      hepatoma MH1C1 cells. Following binding, these amino-terminal and carboxyl
      terminal regions of the 39-kDa protein are each rapidly endocytosed and degraded
      with kinetics identical to the full-length 39-kDa protein. Competition binding
      experiments with these constructs demonstrate that amino-terminal and carboxyl
      terminal regions of the 39-kDa protein compete with one another for binding to
      LRP/alpha 2MR. A model is proposed in which amino-terminal and carboxyl-terminal
      regions of the 39-kDa protein bind to different sites on LRP/alpha 2MR in order
      to inhibit ligand binding.

PMID- 7508910
TI  - Microfilament reorganization is associated with functional activation of alpha M
      beta 2 on monocytic cells.
AB  - Selected agonists convert the leukocyte integrin alpha M beta 2 on monocytes from
      a low to a high affinity state competent to bind factor X and fibrinogen.
      Conformational changes of alpha M beta 2 re hypothesized to account for this
      functional transition. Here we report that cytochalasins known to interfere with
      actin filaments induce the alpha M beta 2 functional transition. Upon exposure to
      cytochalasin B, isolated human blood monocytes and cells of the monocytic cell
      line THP-1 bound 125I-factor X (X) or 125I-fibrinogen (Fg) in a Ca(2+)-dependent,
      saturable manner. Monoclonal antibodies (mAbs) to the alpha M subunit and the
      common beta 2 subunit of leukocyte integrins inhibited X and Fg binding, whereas
      mAbs to the alpha chains of the other leukocyte integrins had no effect. Anti
      alpha M mAb immunoprecipitated 125I-X that had been chemically cross-linked to
      its cognate receptor. Specific binding was not associated with an increased
      surface density of beta 2 integrins consistent with conformational remodeling of
      the receptor. Simultaneous analysis of actin forms in viable monocytes indicated
      a dynamic redistribution of cellular actin. The transient increase in G actin
      concurrent with an agonist action such as cytochalasin or ADP was reversed by an
      increase in F actin coincident with X/Ca2+ binding. A potential role of actin
      redistribution in alpha M beta 2 functional transition is supported by the
      finding that cells in which cellular actin is restricted to G rather than F form
      bound X and initiated a rapid coagulant response. We propose that a transient
      disassembly of actin filaments may relieve constraints on alpha M beta 2 via the
      cytoplasmic domains, permitting the conformational dynamics required for
      recognition of ligands.

PMID- 7508912
TI  - Glucose-induced translocation of protein kinase C isoforms in rat-1 fibroblasts
      is paralleled by inhibition of the insulin receptor tyrosine kinase.
AB  - Rat-1 fibroblasts stably overexpressing high levels of human insulin receptor
      were used as a model system to study the effects of hyperglycemia on insulin
      receptor tyrosine kinase (IRK) activity and protein kinase C (PKC) translocation
      in parallel in the intact cell. Glucose (10-25 mM) induced a significant
      reduction of IRK activity (tyrosine phosphorylation of IR-beta-subunit and IR
      substrate-1) within 10 min. This effect was paralleled by a rapid translocation
      of several PKC isoforms (cPKC alpha, nPKC delta, nPKC epsilon, nPKC zeta) to the
      plasma membrane within 1 min. Kinetics of IRK inhibition and PKC translocation
      are consistent with the idea that the glucose effect on IRK is mediated by PKC
      activation. This hypothesis is supported by further observations. Addition of the
      protein kinase C inhibitor H-7 can prevent the effect of glucose on IRK.
      Inhibition of IRK is also observed after stimulation of the cells with the
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate, which can substitute for a
      physiological activator of PKC. Glucose (25 mM) increases the 32P incorporation
      in serine residues of the beta-subunit of IRK. We conclude that high levels of
      glucose induce inhibition of IRK in vivo. There is indirect evidence that this
      effect is mediated by a glucose-induced PKC translocation/activation and serine
      phosphorylation of the insulin receptor.

PMID- 7508913
TI  - Purification of two immunologically related phosphatidylinositol-(4,5)-
      bisphosphate phosphatases from bovine brain cytosol.
AB  - Two phosphatidylinositol-(4,5)-bisphosphate (PtdIns-(4,5)P2) phosphatase
      activities were isolated from a 45% saturated (NH4)2SO4 fraction of the soluble
      cytosol (100,000 x g supernatant) of bovine cerebral hemispheres by ion-exchange
      chromatography on Q-Sepharose (Q-1 and Q-2). Each was further purified on heparin
      Sepharose, butyl-agarose, and/or Cibacron blue F3GA to yield products of similar
      specific activity (70-100 mumol/min/mg protein, 1000-2000-fold purification).
      Salt was required to stabilize activity and dithiothreitol was required to
      preserve maximum activity and to prevent or reverse aggregation that resisted
      disruption by mercaptoethanol and/or SDS. Monoclonal antibodies were prepared
      that recognized several components in the partially purified preparations.
      Immunoabsorption of activity by monoclonal antibodies that had been chemically
      cross-linked to protein A-Sepharose followed by SDS-polyacrylamide gel
      electrophoresis of absorbed proteins was used to identify the active components
      as a 155-kDa protein in Q-1 and a 115-kDa protein in Q-2. Two antibodies
      recognized different epitopes in the 155-kDa phosphatase. A third antibody
      recognized a common epitope in both phosphatases indicating that the two enzymes
      are related. Both phosphatases were Mg(2+)-dependent, exhibited similar kinetic
      properties, and hydrolyzed PtdIns(4,5)P2 but not PtdIns(4)P, phosphatidic acid,
      or several other phosphate monoesters. They hydrolyzed inositol (1,4,5)
      trisphosphate at 30% of the rate with PtdIns(4,5)P2 and this activity co-purified
      with PtdIns(4,5)P2 phosphatase activity. High molecular weight PtdIns(4,5)P2
      phosphatases may be precursors of lower molecular weight soluble Type II inositol
      polyphosphate-5-phosphatases shown to account for the PtdIns(4,5)P2 phosphatase
      activity in platelets (Matzaris, M., Jackson, S.P., Laxminarayan, M., Speed,
      C.J., and Mitchell, C.A. (1994) J. Biol. Chem. 269, 3397-3402). The three
      antibodies did not inhibit activity but recognized both native and denatured
      (Western blots) phosphatases and should be useful tools to study the
      distribution, structure, and regulation of the two forms of PtdIns(4,5)P2
      phosphatase.

PMID- 7508914
TI  - Proteolytic conversion of single chain precursor macrophage-stimulating protein
      to a biologically active heterodimer by contact enzymes of the coagulation
      cascade.
AB  - Human serum macrophage stimulating protein (MSP) is a disulfide-linked
      heterodimer that induces motile and phagocytic activity of mouse resident
      peritoneal macrophages. It is a member of the family of kringle proteins, which
      typically exist in extracellular fluid as single chain precursors that are
      activated by proteolytic cleavage. In this work, we expressed [35S]cysteine
      labeled recombinant pro-MSP in MSP cDNA-transfected Chinese hamster ovary cells
      and studied proteolytic processing of pro-MSP and the requirement of cleavage for
      biological activity. In media containing heat-inactivated fetal bovine serum, the
      protein was secreted as single chain pro-MSP, which was cleaved over a period of
      hours to the mature heterodimer. Cleavage was prevented by serine protease
      inhibitors such as leupeptin or aprotinin; it did not occur if cells were
      cultured in serum-free medium. Nanomolar concentrations of coagulation proteases
      kallikrein, factor XIIa or factor XIa cleaved pro-MSP to MSP within 30 min. Pro
      MSP had no biological activity. After cleavage by kallikrein, biological activity
      was quantitatively comparable to that of natural MSP isolated from human plasma.
      These results support our hypothesis that MSP circulates as the biologically
      inactive precursor and can be activated by enzymes of the intrinsic coagulation
      cascade.

PMID- 7508915
TI  - 17 alpha-ethinylestradiol increases transcytosis of asialoglycoproteins in rat
      liver.
AB  - We have measured the hepatobiliary transcytosis of asialofetuin (ASF) and low
      density lipoprotein (LDL) in rats following treatment with 5 mg of 17 alpha
      ethinylestradiol/kg of body weight for 3 days. The rate of appearance of both
      ligands in bile was increased 5-fold in estradiol-treated rats compared with
      controls. In contrast, no increase was observed in the transcytosis of dimeric
      IgA. The majority of the ASF recovered from the bile of estradiol-treated rats
      was undegraded, indicating transcytic delivery rather than lysosomal discharge.
      No increase in the rate of endocytosis of ASF was observed. When transcytosis of
      125I-LDL was measured in the presence of excess ASF the rate decreased by
      approximately 70%. Moreover, sialidase treatment of LDL in vitro increased the
      biliary appearance of LDL 2-fold in estradiol-treated rats, suggesting that the
      effect of estradiol on both ligands was mediated via the asialoglycoprotein
      receptor. We conclude that 17 alpha-ethinylestradiol increases the transcytosis
      of ASF and LDL through mechanisms that alter the intracellular trafficking of the
      asialoglycoprotein receptor.

PMID- 7508916
TI  - cAMP abrogates the p21ras-mitogen-activated protein kinase pathway in
      fibroblasts.
AB  - The mechanism by which cAMP inhibits growth factor-induced DNA synthesis in
      fibroblasts is not understood. Here we show that in Rat-1 fibroblasts, cAMP
      raising agents inhibit p21ras-mediated mitogen-activated protein (MAP) kinase
      activation induced by either epidermal growth factor or lysophosphatidic acid.
      Under the same conditions, however, epidermal growth factor- or lysophosphatidic
      acid-induced protein tyrosine phosphorylation, Ca2+ mobilization, and activation
      of Na+/H+ exchange are not attenuated. In ras-transformed Rat-1 cells, 8-bromo
      cAMP rapidly deactivates constitutively active MAP kinase without reducing
      p21ras.GTP levels; long term 8-bromo-cAMP treatment of these cells leads to
      growth arrest and reversion of the transformed phenotype. These results show that
      elevation of intracellular cAMP levels abrogates the p21ras MAP kinase pathway at
      a step downstream of p21ras activation. This finding provides a molecular basis
      for the growth-inhibitory action of cAMP in normal and transformed fibroblasts.

PMID- 7508918
TI  - A novel lipoxygenase from rice. Primary structure and specific expression upon
      incompatible infection with rice blast fungus.
AB  - A novel lipoxygenase cDNA (3,007 base pairs) was isolated from rice leaves (Oryza
      sativa cv. Aichiasahi) which had been infected with an incompatible race of the
      rice blast fungus, Magnaporthe grisea. A single copy of the gene is present in
      the rice genome and encodes a protein of 923 residues with a molecular weight of
      102,714. This gene product shares the least amino acid sequence homology among
      plant lipoxygenases identified to date. A novel feature of this gene product is a
      putative transit peptide sequence at the amino terminus, suggesting the enzyme is
      localized in chloroplasts. An active lipoxygenase was expressed from the cDNA in
      Escherichia coli and characterized. The lipoxygenase introduces molecular oxygen
      exclusively into the C-13 position of linoleic and linolenic acids. The gene is
      expressed at high levels 15 h after inoculation with an incompatible race of M.
      grisea, at a low level after inoculation with a compatible race of the pathogen,
      and is not expressed in mock-infected leaves. Gene expression begins at the same
      time that the pathogen begins to penetrate into leaf tissue. This novel
      lipoxygenase gene expression is a part of the early response of the host to
      pathogenic attack.

PMID- 7508917
TI  - Mitogen-activated protein kinases and ribosomal S6 protein kinases are involved
      in signaling pathways shared by interleukin-11, interleukin-6, leukemia
      inhibitory factor, and oncostatin M in mouse 3T3-L1 cells.
AB  - The mechanisms of signaling pathways shared by interleukin (IL)-11, IL-6,
      leukemia inhibitory factor (LIF), and oncostatin M (ONC) remain elusive. We
      report here that treatment of 3T3-L1 cells with IL-11, IL-6, LIF, and ONC induces
      overlapping but distinct patterns of tyrosine phosphorylation and activates
      indistinguishable primary response genes. We further demonstrate for the first
      time that IL-11, IL-6, LIF, and ONC can trigger the activation of mitogen
      activated protein kinases and the 85-92-kDa ribosomal S6 protein kinase
      (pp90rsk). In addition, our data also show that preincubation of cells with a
      tyrosine kinase inhibitor herbimycin A, but not with a serine/threonine kinase
      inhibitor H7, blocks activation of mitogen-activated protein kinases and pp90rsk.
      Interestingly, H7, but not herbimycin A, inhibits pp90rsk activity in the in
      vitro kinase assays. These results suggest that pp90rsk is one of the potential
      candidates for the H7-sensitive protein kinase(s), which is critical for the
      activation of primary response genes by these cytokines.

PMID- 7508919
TI  - Thyrotropin-releasing hormone stimulates MAP kinase activity in GH3 cells by
      divergent pathways. Evidence of a role for early tyrosine phosphorylation.
AB  - Regulation of the mitogen-activated protein (MAP) kinase by thyrotropin-releasing
      hormone (TRH) in GH3 rat pituitary tumor cells was investigated. Both TRH and
      epidermal growth factor (EGF) acutely activated this enzyme, via tyrosine and
      serine/threonine phosphorylation. Down-regulation of cellular protein kinase C
      (PKC) only partly inhibited the phosphorylation of MAP kinase by TRH, suggesting
      both PKC-dependent and -independent pathways. Both TRH and EGF similarly
      increased the phosphorylation of raf-1, by a PKC-independent mechanism. Both TRH
      and EGF stimulated the formation of a ras-GTP complex. This activation of ras by
      growth factors is thought to involve the tyrosine phosphorylation of Shc. EGF
      stimulated the tyrosine phosphorylation of three Shc proteins and their
      subsequent association with its receptor. TRH stimulated the tyrosine
      phosphorylation of the 52-kDa Shc protein, although neither phorbol esters nor
      the calcium ionophore A23187 had any effect, indicating that this effect of TRH
      was not dependent on PKC. Both TRH and EGF induced the association of tyrosine
      phosphorylated Shc proteins with a fusion protein containing SH2 and SH3 domains
      of Grb2, another important component in ras activation. These results provide
      evidence that MAP kinase is acutely activated by TRH through a PKC-dependent
      pathway as well as a second pathway possibly involving tyrosine phosphorylation.

PMID- 7508920
TI  - p95, the major phosphotyrosine-containing protein in mouse spermatozoa, is a
      hexokinase with unique properties.
AB  - Mouse sperm contain a major phosphotyrosine-containing protein of M(r) 95,000
      (nonreducing conditions) which has been implicated as a sperm membrane receptor
      for the egg zona pellucida glycoprotein, ZP3 (Leyton, L., and Saling, P. (1989)
      Cell 57, 1123-1130; Leyton, L., LeGuen, P., Bunch, D., and Saling, P. (1992)
      Proc. Natl. Acad. Sci. U. S. A. 89, 11692-11695). This protein was purified and
      subjected to limited tryptic digestion and subsequent amino acid analysis. Three
      sequenced peptides revealed 100% amino acid identity to a mouse hepatoma
      hexokinase (Arora, K. K., Fanciulli, M., and Pederson, P. L. (1990) J. Biol.
      Chem. 265, 6481-6488). The purified protein, which migrated at M(r) 116,000 under
      reducing conditions (p95/116), reacted with an antiserum to the purified rat
      brain hexokinase, type 1, and comigrated on sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis with the purified rat brain enzyme under both nonreducing and
      reducing conditions. Unlike p95/116, the rat brain enzyme was not a
      phosphotyrosine-containing protein. The p95/116 protein could be
      immunoprecipitated with the hexokinase antiserum or an O-phosphotyrosine
      antibody. Limited tryptic digestion of the purified p95/116 and the rat brain
      enzyme generated subsets of identical peptides which reacted with the hexokinase
      antiserum. However, p95/116 also contained phosphotyrosine-containing peptides
      that were not present in the rat brain hexokinase. When different mouse tissues
      were probed with the hexokinase antiserum all tissues, with the exception of
      liver, contained immunoreactive protein. In contrast, only sperm and testis
      possessed a phosphotyrosine-containing form of hexokinase. These data suggest
      that the germ cell component of the testis possesses a unique tyrosine
      phosphorylated form of hexokinase.

PMID- 7508921
TI  - Mast cell protease inhibitor, trypstatin, is a fragment of inter-alpha-trypsin
      inhibitor light chain.
AB  - The mast cell protease inhibitor trypstatin was purified from rat peritoneal mast
      cells (Kido, H., Yokogoshi, Y., and Katunuma, N. (1988) J. Biol. Chem. 263, 18104
      18107). We noticed that trypstatin could possibly be identical with the second
      half of inter-alpha-trypsin inhibitor light chain (ITI-LC), because only 5 amino
      acid residues of trypstatin are different from the sequence deduced from the
      recently reported rat ITI-LC mRNA. Southern blot analysis revealed that a 170
      base pair probe corresponding to the second half of rat ITI-LC hybridized to the
      digested rat genomic DNAs only at single bands even in low stringency conditions.
      Similarly, a 170-base pair probe corresponding to the human counterpart, which
      differs by 10 deduced amino acids from the rat probe, also hybridized to the
      digested rat genomic DNAs only at single bands at the same positions and same
      conditions. These results suggest that rat trypstatin is genetically identical
      with rat ITI-LC. ITI-LC/trypstatin mRNA was not detected in rat peritoneal mast
      cells by RNA blot nor by reverse transcription-polymerase chain reaction
      analysis. Since trypstatin was purified from rat peritoneal mast cells and the
      cells were immunohistochemically positive with anti ITI-LC antibody, ITI
      LC/trypstatin may be taken up into mast cell granules from the serum but may not
      be generated by mast cells themselves.

PMID- 7508922
TI  - Molecular cloning and expression of a cDNA of the bovine prostaglandin F2 alpha
      receptor.
AB  - Capitalizing on the significant sequence homology comprising the transmembrane
      motif regions of known prostanoid receptor family, we targeted the cloning of a
      cDNA clone for prostaglandin (PG) F2 alpha receptor from a bovine corpus luteum
      cDNA library. By using several pairs of degenerated primers created from a common
      motif of transmembrane domains, polymerase chain reaction gave a clone SN463
      carrying the homologous sequence, which covered transmembrane motif IV-VI of the
      thromboxane (TX) A2 receptor. This polymerase chain reaction product was used as
      a DNA probe for the following cross-hybridization, and a clone BC2211 carrying a
      2.2-kilobase pair DNA insert was isolated. This clone encodes a protein of 362
      amino acid residues (M(r) = 40,983) with seven potential transmembrane domains
      and represented significant overall sequence homology to human TXA2 receptor
      protein (34% in amino acid). Injection of the mRNA synthesized in vitro from the
      cloned cDNA into a Xenopus oocyte elicited electrophysiological response to PGF2
      alpha. Ligand binding displacement in membranes of mammalian COS-7 cells
      transfected with the cDNA indicated the rank order of affinity of the receptor to
      PGs: PGF2 alpha > PGD2 > PGE2 > STA2, a TXA2 agonist. PGF2 alpha activated
      inositol phosphate formation in COS-7 cells transfected with receptor cDNA.
      Northern blot analysis and in situ hybridization indicated that the PGF2 alpha
      receptor mRNA is highly expressed and accumulated in corpus luteum. This is the
      first report on a successful cloning of functional receptor cDNA for PGF2 alpha.

PMID- 7508924
TI  - Localization of the type 3 inositol 1,4,5-trisphosphate receptor in the Ca2+ wave
      trigger zone of pancreatic acinar cells.
AB  - Agonist-induced cytosolic Ca2+ (Ca2+i) signals begin as apical-to-basal Ca2+i
      waves in pancreatic acinar cells and in other polarized epithelia. However, the
      basis of this polarized Ca2+i signaling pattern is unknown. Here we use
      immunocytochemistry to demonstrate that the type 3 inositol trisphosphate
      receptor is localized to the extreme apex of pancreatic acinar cells, the region
      which corresponds to the trigger zone from which Ca2+i signals originate in this
      cell type (Kasai, H., Li, Y.X., and Miyashita, Y. (1993) Cell 74, 669-677). We
      also show that inositol trisphosphate-mediated Ca2+ release induces amylase
      release from permeabilized pancreatic acini. Since Ca2+i signals begin by
      inositol trisphosphate-mediated Ca2+ release, these findings suggest that
      localization of the type 3 inositol trisphosphate receptor to the trigger zone is
      responsible for the generation of apical-to-basal Ca2+i waves, and that this
      organization may be important for regulating apical exocytosis in pancreatic
      acinar cells.

PMID- 7508923
TI  - Tyrosine phosphorylation of the gamma subunit of Fc gamma receptors, p72syk, and
      paxillin during Fc receptor-mediated phagocytosis in macrophages.
AB  - Fc receptor-mediated phagocytosis in mouse macrophages occurs by a tyrosine
      kinase-dependent pathway (Greenberg, S., Chang, P., and Silverstein, S.C. (1993)
      J. Exp. Med. 177, 529-534). To identify proteins that are phosphorylated on
      tyrosine residues during phagocytosis, we used anti-phosphotyrosine antibodies to
      perform immunoblotting and immunoprecipitation of lysates derived from Fc
      receptor-stimulated macrophages. Proteins of 26, 30, 35, 37, 40, 43, 47, 56, 60,
      68, 83, 116, and 150 kDa displayed enhanced tyrosine phosphorylation during Fc
      receptor-mediated phagocytosis. Tyrosine phosphorylation of these proteins was
      not a consequence of actin polymerization since treatment with cytochalasin D did
      not alter the pattern of Fc receptor-stimulated protein tyrosine phosphorylation.
      The 68-kDa tyrosine phosphoprotein was identified as paxillin, a cytoskeletal
      associated tyrosine kinase substrate previously identified in fibroblasts and
      shown to localize to focal adhesions (Turner, C.E., Glenney, J.R., and Burridge,
      K. (1990) J. Cell Biol. 111, 1059-1068). Paxillin colocalized with F-actin
      beneath nascent phagosomes. In addition to the above proteins detected by anti
      phosphotyrosine immunoblotting, the gamma subunit of FcRI and III was shown to
      undergo tyrosine phosphorylation during Fc receptor-mediated phagocytosis. Of
      several candidate tyrosine kinases that may be activated during Fc receptor
      stimulation, p72syk, but not p125FAK, displayed enhanced tyrosine phosphorylation
      during Fc receptor aggregation. The coordinated tyrosine phosphorylation of the
      gamma subunit of macrophage Fc receptors, the tyrosine kinase syk, and the
      cytoskeletal-associated protein, paxillin, may be important steps in integrating
      signals between Fc receptors and the underlying cytoskeleton.

PMID- 7508925
TI  - Growth hormone induces a DNA binding factor related to the interferon-stimulated
      91-kDa transcription factor.
AB  - Signaling mechanisms leading to regulation of gene transcription by growth
      hormone (GH) and other molecules that signal via the cytokine receptor family
      have been elusive. Based upon recent findings that GH and interferons activate
      JAK family tyrosine kinases, we have identified a novel signaling pathway leading
      from the GH receptor to the nucleus. We report that in 3T3-F442A fibroblasts, GH
      stimulates tyrosyl phosphorylation of a protein recognized by antibody to p91, a
      component of DNA-binding complexes that are activated by tyrosyl phosphorylation
      in response to interferons alpha and gamma. In addition, a GH-inducible DNA
      binding factor (GHIF) is identified that binds to the c-sis-inducible element of
      the c-fos promoter. GHIF contains a protein antigenically related to p91 and is
      tyrosyl-phosphorylated. These findings indicate that in signaling between their
      receptors and the nucleus, GH and interferons utilize related or identical
      components, including JAK family tyrosine kinases and proteins in the p91 family.
      When combined with recent findings that many members of the cytokine receptor
      family activate JAK kinases, including some cytokines that activate p91-related
      proteins, these findings suggest that signaling pathways involving JAK kinases
      and p91 family members may be broadly distributed.

PMID- 7508926
TI  - Role of transcription factor NF-kappa B/Rel in induction of nitric oxide
      synthase.
AB  - The promoter of the murine gene encoding inducible nitric oxide synthase (iNOS)
      contains an NF-kappa B site beginning 55 base pairs upstream of the TATA box,
      designated NF-kappa Bd. Reporter constructs containing truncated promoter
      regions, when transfected into macrophages, revealed that NF-kappa Bd is
      necessary to confer inducibility by bacterial lipopolysaccharide (LPS).
      Oligonucleotide probes containing NF-kappa Bd plus the downstream 9 or 47 base
      pairs bound proteins that rapidly appeared in the nuclei of LPS-treated
      macrophages. The nuclear proteins bound to both probes in an NF-kappa Bd
      dependent manner, but binding was resistant to cycloheximide only for the shorter
      probe. The proteins binding both probes reacted with antibodies against p50 and c
      rel but not RelB; those binding the shorter probe also reacted with anti-RelA
      (p65). Pyrrolidine dithiocarbamate, which acts as a specific inhibitor of NF
      kappa B, blocked both the activation of the NF-kappa Bd-binding proteins and the
      production of NO in LPS-treated macrophages. Thus, activation of NF-kappa B/Rel
      is critical in the induction of iNOS by LPS. However, additional, newly
      synthesized proteins contribute to the NF-kappa Bd-dependent transcription factor
      complex on the iNOS promoter in LPS-treated mouse macrophages.

PMID- 7508927
TI  - Induction of specific protein tyrosine phosphatase transcripts during
      differentiation of mouse erythroleukemia cells.
AB  - We reported previously that most of the phosphotyrosine-containing cellular
      proteins were quickly dephosphorylated at the very early stage of erythroid
      differentiation of mouse erythroleukemia (MEL) cells. These and other
      experimental results implicated a specific protein tyrosine phosphatase(s)
      (PTPase(s)) involved in the commitment of the erythroid differentiation. We have
      investigated the pattern of transcripts of PTPases during MEL cell
      differentiation and found that while the transcripts of most PTPases were
      unchanged or undetected in the cells, transcripts for two PTPases (PTP beta 2 and
      RIP) exhibited distinct patterns of induction at a very early stage of
      differentiation. Some of the mutant cells defective in differentiation did not
      show the induction of these PTPase transcripts. We discuss the possible role
      played by the PTPases in the commitment of MEL cell differentiation.

PMID- 7508928
TI  - Arachidonic acid stimulates the plasma membrane H+ conductance of macrophages.
AB  - When activated, phagocytes undergo a large burst of metabolic acid production.
      Deleterious cytosolic acidification is prevented by extrusion of H+ (equivalents)
      through specific transport systems, including a recently described H+ conductive
      pathway. The conductance can be activated by cytosolic acidification and by
      depolarization, events known to occur during phagocyte activation. It is
      possible, however, that the conductance is also directly stimulated by agonists
      or second messengers. In this report, spectroscopic and electrophysiological
      determinations were used to assess the effects of arachidonic acid (AA), a potent
      phagocyte stimulant, on the plasmalemmal H+ conductance of murine macrophages. AA
      greatly enhanced the slowly activating H+ currents and the cytosolic
      alkalinization triggered by depolarizing pulses. The H+ current in AA-treated
      cells appeared at more negative potentials and its activation and deactivation
      became faster. The ionic selectivity, outward rectification, and pharmacological
      properties of the stimulated current were identical to those of the basal
      current, suggesting that AA acts by facilitating the activation of the endogenous
      H+ conductive pathway, rather than by exerting a protonophoric effect.
      Experiments using specific inhibitors suggested that the effects of AA are not
      mediated by lipo- or cyclooxygenase. Comparison of the effects of a variety of
      fatty acids supported this conclusion. The order of potency to stimulate the
      conductance was: AA > palmitoleate approximately palmitelaidate > linoleate >
      oleate > elaidate. Saturated fatty acids were inactive. This sequence shows
      striking similarity with the ability of these lipids to stimulate the NADPH
      oxidase. The results indicate that, simultaneously with the activation of
      metabolic acid generation, phagocyte agonists also directly activate regulatory
      H+ extrusion, thereby favoring maintenance of intracellular pH in the
      physiological range.

PMID- 7508930
TI  - Design and synthesis of amphipathic 3(10)-helical peptides and their interactions
      with phospholipid bilayers and ion channel formation.
AB  - It has been reported that a peptide corresponding to the S4 segment in sodium
      channel protein is able to form voltage-dependent cation-selective ion channels
      (Tosteson, M. T., Auld, D. S., and Tosteson, D. C. (1989) Proc. Natl. Acad. Sci.
      U. S. A. 86, 707-710). However, biological and other physical properties remain
      unexamined. In the present study, three peptides, H-(Ala-Arg-Leu)8-OH (ARL8), H
      (Val-Arg-Leu)8-OH (VRL8), and H-(Leu-Arg-Leu)8-OH (LRL8) which were designed on
      the basis of the S4 segment and expected to form 3(10)-helix, were synthesized
      and examined with regard to conformational change by the interaction with
      membranes, membrane perturbation ability, ion channel formation, and
      antimicrobial activity. According to CD spectra, these peptides were found to
      form a 3(10)-helical structure in the presence of dipalmitoyl-DL-alpha
      phosphatidylcholine/dipalmitoyl-DL-alpha- phosphatidylglycerol (3:1) liposomes.
      The experiment of the peptide-induced leakage of carboxyfluorescein from
      liposomes showed that all the peptides had a strong ability to perturb membranes.
      The peptides were able to form cation-selective ion channels in planar asolectin
      lipid bilayers. The conductances of the ion channels were small (approximately 2
      picosiemens for VRL8 and LRL8 and approximately 23 picosiemens for ARL8),
      suggesting that the peptides produce narrow pores or wider pores with certain
      permeable barriers that are a portion of the whole channels. The differences in
      their conductances depend possibly on the sizes of the side chains of Ala, Val,
      and Leu residues. However, non of the peptides showed antimicrobial activity
      (minimum inhibitory concentrations, > 50 micrograms/ml). Here, we present the
      first evidence that the peptides can form 3(10)-helical structures with long
      chain lengths in a lipid bilayer environment.

PMID- 7508929
TI  - The modulation of protein kinase C activity by membrane lipid bilayer structure.
AB  - The hypothesis that protein kinase C (PKC) activity is sensitive to phospholipid
      head group interactions was tested using lipid bilayers of defined composition
      with PKC purified from rat brain. The head group interactions were modulated by
      varying phosphatidylcholine cis-unsaturation, vesicle curvature, and by the
      addition of phosphatidylethanolamine and cholesterol. With unilamellar vesicles
      (including 20 mol% brain phosphatidylserine), increased phosphatidylcholine
      unsaturation potentiated basal and phorbol ester stimulated PKC activity. By
      contrast, in the presence of phosphatidylethanolamine, the activity decreased
      with increasing phosphatidylcholine unsaturation. Weakening phospholipid head
      group interactions spaces the head group region and increases interstitial water,
      and this effect was assessed from its effect on the fluorescence intensity of the
      phospholipid-labeled fluorophore 1-palmitoyl-2-N-(4-nitrobenzo-2-oxa-1,3
      diazole)aminohexanoylphosphat idylcholin e (C6-NBD-PC). When the PKC activities
      with vesicles of varying phosphatidylcholine unsaturation, with and without
      phosphatidylethanolamine, were plotted as a function of the fluorescence
      intensity of C6-NBD-PC-labeled vesicles, a biphasic profile was obtained, which
      had an optimum value of intensity, relating to head group spacing, that
      corresponded to a maximal enzyme activity. A similar biphasic curve was also
      found when PKC activities were plotted as a function of published bilayer
      intrinsic curvature x-ray diffraction data, a parameter closely related to head
      group spacing. By contrast, no simple relationship was evident between PKC
      activity and 1,6-diphenyl-1,3,5-hexatriene anisotropy, taken as a measure of
      lipid order or fluidity. Therefore, increasing the level of phosphatidylcholine
      unsaturation, phosphatidylethanolamine, or cholesterol either potentiates or
      attenuates PKC activity, dependent on whether the initial condition is above or
      below its optimum.

PMID- 7508931
TI  - Expression of the beta subunit of chorionic gonadotropin in transgenic mice.
AB  - Transcriptional activation of the chorionic gonadotropin (CG) genes is linked to
      trophoblast differentiation. In a multistep process, cytotrophoblasts expressing
      only the alpha subunit differentiate into intermediates that coexpress the CG
      beta subunit. To study the regulation of expression of the CG beta genes in vivo,
      we constructed mice carrying a 36-kilobase cosmid insert containing the six CG
      beta genes. In the placenta of all three constructed lines, expression occurred
      at approximately 1% of the levels in first trimester human placenta. The amount
      of CG beta mRNA in mouse placenta was a function of gestational age; however, in
      contrast to the human placenta where CG beta peaks early in pregnancy, CG beta
      transcripts were only detectable in the mouse placenta late in gestation, i.e.
      from day 14 onward. Human CG beta was expressed also in cerebral cortex,
      pituitary, and at minute levels in adrenal. Pituitary CG beta expression was
      significantly lower than in placenta. Unexpectedly, transcripts were observed in
      cerebral cortex at levels comparable with the placenta. Most of the CG beta
      transcripts in mouse placenta are derived from CG beta genes 5, 3, and 8, in a
      ratio similar to that found in human placenta. In contrast, only CG beta genes 1
      and 2 were transcribed in transgenic mouse brain; open reading frames from the CG
      beta 1 and beta 2 transcripts differ substantially from the CG beta protein. The
      data show that although the mouse lacks a CG beta-like gene, the human CG beta
      genes are transcribed in a regulated fashion in mouse placenta. Moreover, the
      stage-specific induction of the transgene suggests that mouse placental cells may
      express CG beta in an intermediate cell comparable with that seen in human
      placenta. Taken together, these data suggest that transgenic mice can be used as
      a model for elucidating the mechanisms involved in regulated expression of the CG
      beta gene cluster in vivo. Additionally, a different subset of CG beta genes (CG
      beta 1 and beta 2) is active in the mouse brain.

PMID- 7508932
TI  - Shc phosphorylation in myeloid cells is regulated by granulocyte macrophage
      colony-stimulating factor, interleukin-3, and steel factor and is constitutively
      increased by p210BCR/ABL.
AB  - Granulocyte macrophage colony-stimulating factor, interleukin-3, and steel factor
      induce proliferation of hematopoietic cells through binding to specific, high
      affinity, cell surface receptors. However, little is known about post-receptor
      signal transduction pathways. Here we report that an SH2 domain containing
      protein previously implicated in the activation of p21ras, Shc, is transiently
      tyrosine phosphorylated in myeloid cells after stimulation with granulocyte
      macrophage colony-stimulating factor, interleukin-3, or steel factor. Also, Shc
      was found to be constitutively tyrosine phosphorylated in myeloid cell lines made
      factor independent by expression of p210BCR/ABL. A Shc-associated 140-kDa protein
      was identified, which was phosphorylated on tyrosine residues transiently after
      cytokine stimulation and constitutively after expression of p210BCR/ABL. These
      findings suggest that Shc could play an important role in a signal transduction
      pathway, which leads to the proliferation of myeloid cells.

PMID- 7508933
TI  - Induction of iron-derived EPR signals in murine cancers by nitric oxide. Evidence
      for multiple intracellular targets.
AB  - The cell-mediated immune response to syngeneic tumors activates the cytokine
      inducible nitric oxide synthase. We observed that syngeneic murine tumors
      exhibited EPR signals related to iron-nitrosyl complex formation. Three different
      EPR active iron-nitrosyl species were observed, an Fe(RS)2(NO)2 signal and two
      differentiable heme-nitrosyl complexes. Hemoglobin assays showed that the heme
      nitrosyl signals were not derived from contaminating hemoglobin. Signal
      amplitudes were attenuated in mice treated with N omega-mono-methyl-L-arginine
      (MLA), an inhibitor of nitric oxide synthase. Tumors grown in vivo contained EPR
      signals while those grown in culture without continuing cytokine stimulation lost
      the signals after a few days. Cultured cells that were treated with cytokines, or
      that were cocultivated with cytokine-activated macrophages, regained EPR active
      complexes. These results show that the cell-mediated immune response to syngeneic
      tumors involves the induction of nitric oxide synthase. While nitric oxide
      synthesis is induced in both tumor infiltrating macrophages and in the tumor
      cells themselves, only tumor cells contributed to formation of heme-nitrosyl
      complexes. This result indicates the presence of a novel intracellular target for
      NO within tumor cells.

PMID- 7508934
TI  - Regulation of endocytic trafficking and acidification are independent of the
      cystic fibrosis transmembrane regulator.
AB  - Cystic fibrosis is associated with mutations of the cystic fibrosis transmembrane
      regulator (CFTR), a cAMP-regulated plasma membrane Cl- channel. Mutations in the
      CFTR have been reported to not only impair Cl-transport at the plasma membrane
      but also inhibit organelle acidification and disrupt cAMP-regulated plasma
      membrane recycling. Comparisons of cultured pancreatic adenocarcinoma cells
      expressing the delta 508 mutant CFTR (CFPAC-1 cells) with genetically matched
      CFPAC-1 cells transfected with the wild-type CFTR demonstrate that expression of
      wild-type CFTR restores cAMP-mediated plasma membrane Cl- transport, but has no
      effect on pH regulation of endosomes labeled with either transferrin or wheat
      germ agglutinin. Endosome pH was, in all cases, similar in the two cell lines and
      unaffected by treatment with the cAMP agonist forskolin. Forskolin treatment had
      no effect on transferrin internalization, but increased recycling by 30-40% in
      both cell lines. The kinetics of wheat germ agglutinin recycling were negligibly
      affected by forskolin in either cell line. These results demonstrate that
      endocytic acidification and cAMP-mediated endocytic protein redistribution are
      similar in genetically matched CFPAC-1 cells which differ only in the expression
      of mutant or wild-type CFTR.

PMID- 7508935
TI  - Activation of receptor-associated tyrosine kinase JAK2 by prolactin.
AB  - JAK family tyrosine kinases have recently been implicated in intracellular signal
      transduction by transmembrane cytokine receptors of the interferon (IFN) and
      hematopoietin receptor families. Using the prolactin (PRL)-dependent rat pre-T
      cell line Nb2, a PRL receptor-associated, candidate tyrosine kinase of 120-130
      kDa was recently characterized (1). In the present work this protein is
      identified as JAK2, based upon reciprocal anti-JAK2 and anti-phosphotyrosine
      immunoprecipitation and immunoblotting. JAK2 underwent rapid and transient
      tyrosine phosphorylation in response to receptor activation, reaching peak levels
      within 5 min of exposure to 100 nM PRL at 37 degrees C. In vitro tyrosine kinase
      assays using either [gamma-32P]ATP and autoradiography or unlabeled ATP combined
      with anti-phosphotyrosine immunoblotting, demonstrated that the activity of JAK2
      was stimulated by PRL. Phosphoamino acid analysis of JAK2 after in vitro tyrosine
      kinase assay revealed that the majority of phosphate was incorporated into
      tyrosine residues. Furthermore, JAK2 was associated with PRL receptors to a
      comparable extent before and after PRL binding, as demonstrated by anti-receptor
      immunoprecipitation and subsequent anti-JAK2 immunoblotting. We propose that
      binding of ligand to the PRL receptor activates preassociated JAK2, and that this
      enzyme generates the initial signal in the intracellular communication cascade.

PMID- 7508936
TI  - Monoamine-activated alpha 2-macroglobulin binds trk receptor and inhibits nerve
      growth factor-stimulated trk phosphorylation and signal transduction.
AB  - Monoamine-activated alpha 2-macroglobulin (alpha 2M) has been shown to inhibit
      beta-nerve growth factor (NGF)-promoted neurite outgrowth and the survival of
      embryonic sensory and forebrain neurons, whereas normal alpha 2M has little or no
      such activity. The objective of this study is to elucidate the mechanism of
      inhibition by monoamine-activated alpha 2M. Methylamine-activated alpha 2M (MA
      alpha 2M) and serotonin-activated alpha 2M (5HT-alpha 2M) dose dependently
      inhibit NGF-promoted neurite outgrowth of the pheochromocytoma PC12 cell and its
      subline PC12(6-24) which overexpresses human trk protooncogene product, but have
      no effect on their viability, and this inhibition can be blocked by high
      concentrations of NGF. The binding of MA-alpha 2M to trk, which is a part of high
      affinity NGF receptor, was studied with PC12(6-24) cells and NIH-3T3 fibroblasts
      expressing trk (trk-3T3). In each case MA-alpha 2M readily forms stable complexes
      with trk in vivo, whereas normal alpha 2M does not. Both 5HT-alpha 2M and MA
      alpha 2M also dose dependently block NGF-promoted autophosphorylation of trk in
      vivo, whereas normal alpha 2M and plasmin-reacted alpha 2M are inactive or much
      less active. MA-alpha 2M also blocks NGF-promoted incorporation of 32P from
      [32P]ATP into trk receptors in vitro. Neither MA-alpha 2M, 5HT-alpha 2M, nor
      normal alpha 2M, however, blocks either platelet-derived growth factor-stimulated
      or epidermal growth factor-stimulated tyrosine phosphorylation of the respective
      receptors. Tyrosine phosphorylation of two of the intracellular substrates,
      phospholipase C-gamma 1 and extracellular signal-regulated kinase-2, in the NGF
      promoted pathways is also dose dependently blocked by MA-alpha 2M. However, by
      comparison MA-alpha 2M is more effective in inhibiting the activation of
      phospholipase C-gamma 1 than trk. We conclude that monoamine-activated alpha 2M
      may block neurite outgrowth and neuronal survival by its specific binding to NGF
      receptors, thus inhibiting the NGF-promoted activation of intracellular second
      messenger pathways.

PMID- 7508937
TI  - rel Is rapidly tyrosine-phosphorylated following granulocyte-colony stimulating
      factor treatment of human neutrophils.
AB  - Stimulation of neutrophils with granulocyte-colony stimulating factor (G-CSF)
      results in an enhanced respiratory burst, prolonged survival, and increased tumor
      cell killing. The effects of G-CSF are mediated by binding to specific, high
      affinity receptors. G-CSF receptors lack intrinsic tyrosine kinase activity, but
      activation of the receptor results in the rapid induction of tyrosine kinase
      activity. Antiphosphotyrosine immunoblots of whole cell lysates prepared from
      neutrophils show that the G-CSF rapidly induces prominent tyrosine
      phosphorylation of a protein of a relative molecular mass of 80 kDa. Using
      monospecific antibodies, the 80-kDa tyrosine-phosphorylated protein has been
      shown to be p80c-rel, a proto-oncogene belonging to a family of transcriptional
      regulators which include NF-kB. The induction of tyrosine phosphorylation of p80c
      rel was unique to G-CSF in that granulocyte-macrophage colony stimulating factor
      which also stimulates neutrophils and induces tyrosine phosphorylation does not
      result in tyrosine phosphorylation of p80c-rel. The consequences of p80c-rel
      tyrosine phosphorylation are not yet known; however, tyrosine-phosphorylated p80c
      rel is capable of binding to DNA, and G-CSF stimulation results in an increase in
      the amount of p80c-rel which binds to DNA. These results demonstrate that one of
      the first biochemical events which occurs in neutrophils following G-CSF
      stimulation, activation of a tyrosine kinase, leads directly to the tyrosine
      phosphorylation of p80c-rel. Thus, the tyrosine kinase activated by G-CSF appears
      to directly transduce a signal to a protein which functions as a transcriptional
      regulator.

PMID- 7508938
TI  - Multiple cytokines activate phosphatidylinositol 3-kinase in hemopoietic cells.
      Association of the enzyme with various tyrosine-phosphorylated proteins.
AB  - Activation of phosphatidylinositol (PI) 3-kinase is a common sequel to tyrosine
      kinase activation and appears to be essential for tyrosine kinases to induce
      proliferation. Since multiple hemopoietic growth factors activate tyrosine
      kinases, we investigated whether these growth factors activate PI 3-kinase. We
      show that interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5),
      granulocyte-macrophage colony stimulating factor (GM-CSF), and steel factor (SLF)
      all activate PI 3-kinase. These cytokines increased the amount of PI 3-kinase
      activity that could be immunoprecipitated with anti-phosphotyrosine antibodies
      from the MC-9 mast cell line or from the hemopoietic progenitor cell line FDC-P1.
      Increases in this assay frequently correlate with PI 3-kinase activation in vivo.
      To determine directly whether these factors activate PI 3-kinase in vivo, we
      measured the levels of 3-phosphorylated inositol phospholipids in intact 32P
      labeled MC-9 cells. IL-3, IL-4, IL-5, GM-CSF, and SLF all caused increased
      synthesis of the PI 3-kinase products phosphatidylinositol 3,4-bisphosphate and
      phosphatidylinositol 3,4,5-trisphosphate with a relative potency of SLF >> IL-3 >
      IL-5, GM-CSF > IL-4. In contrast, IL-4 caused the largest increase in the in
      vitro anti-phosphotyrosine immune complex PI 3-kinase assay. Thus, the in vitro
      assay does not accurately reflect in vivo activation of PI 3-kinase. Cytokine
      treatment did not stimulate tyrosine phosphorylation of either the 85-kDa
      regulatory subunit or the 110-kDa catalytic subunit of PI 3-kinase and is
      therefore not required for activation of PI 3-kinase by these factors. Cytokine
      treatment did induce PI 3-kinase to associate with other tyrosine-phosphorylated
      proteins in a cytokine-specific manner. PI 3-kinase associated with c-kit after
      SLF stimulation, a 170-kDa protein after IL-4 stimulation, and a 70-kDa protein
      after treatment with IL-3 or GM-CSF. Thus, multiple hemopoietic growth factors
      that act through different types of receptors activate PI 3-kinase in vivo and
      induce factor-specific interactions of PI 3-kinase with other tyrosine
      phosphorylated proteins.

PMID- 7508939
TI  - Multiple sites of phosphorylation within the alpha heavy chain of Chlamydomonas
      outer arm dynein.
AB  - We have examined the phosphorylation of the alpha dynein heavy chain (DHC) from
      the outer arm of the Chlamydomonas flagellum. Quantitative analysis indicates
      that this DHC is phosphorylated at a minimum of six sites. Using previously
      identified proteolytic and photocleavage sites (King, S. M., and Witman, G. B.
      (1988) J. Biol. Chem. 263, 9244-9255), we have mapped two regions that are
      phosphorylated in vivo. One is located in a 20-kDa section immediately N-terminal
      to the site of V1 photocleavage. Thus, this region is close to the ATP hydrolytic
      site and also to the predicted junction between the head and stem domains of the
      particle. The second encompasses the 90-kDa C-terminal region of the molecule. In
      this latter section, at least one site is found in an approximately 2-kDa region
      close to domains that are predicted to adopt a coiled-coil structure in those
      DHCs that have been sequenced. The alpha DHC also is specifically labeled by
      endogenous kinases in demembranated, washed axonemes, suggesting that at least
      one alpha DHC kinase is located close to, or is a component of, the outer arm in
      situ.

PMID- 7508940
TI  - A stereophotogrammetric method for determining in situ contact areas in
      diarthrodial joints, and a comparison with other methods.
AB  - Determination of contact areas in diarthrodial joints is necessary for
      understanding the state of stress within the articular cartilage layers and the
      supporting bony structures. The present study describes the use of a
      stereophotogrammetry (SPG) system [Huiskes et al., J. Biomechanics 18, 559-570
      (1985) and Ateshian et al., J. Biomechanics 24, 761-776 (1991)] for determining
      contact areas in diarthrodial joints, using a surface proximity concept similar
      to the one used by Scherrer et al. [ASME J. biomech. Engng 101, 271-278 (1979)].
      This method consists of evaluating the proximity of the articular surfaces to
      determine joint contact areas using precise geometric models of the joint
      surfaces obtained from the SPG system, and precise kinematic data, also obtained
      from SPG. In this study, the SPG method for determining contact areas is compared
      to other commonly used methods such as dye staining, silicone rubber casting and
      Fuji film contact measurement techniques which have been often used and reported
      by other investigators. The bovine glenohumeral joint and the bovine lateral
      tibiofemoral articulation (without the meniscus) were used to represent congruent
      and incongruent joints, respectively. While all the methods yielded consistent
      contact patterns for the incongruent tibiofemoral articulations, the results for
      the congruent bovine glenohumeral joints showed that the SPG and Fuji film
      methods were in better agreement than those obtained from the dye staining and
      silicone rubber casting methods. The advantages of the new SPG method are that it
      can be used for intact joints, and used repeatedly and quickly thus making
      contact-area movement analyses possible [Soslowsky et al., J. orthop. Res. 10,
      524-534 (1992)]. The results of this comparison study show that the SPG technique
      is a reliable and versatile method for determining contact areas in diarthrodial
      joints.

PMID- 7508942
TI  - Arrangement of domains, and amino acid residues required for binding of vascular
      cell adhesion molecule-1 to its counter-receptor VLA-4 (alpha 4 beta 1).
AB  - Interaction of the vascular cell adhesion molecule (VCAM-1) with its counter
      receptor very late antigen-4 (VLA-4) (integrin alpha 4 beta 1) is important for a
      number of developmental pathways and inflammatory functions. We are investigating
      the molecular mechanism of this binding, in the interest of developing new anti
      inflammatory drugs that block it. In a previous report, we showed that the
      predominant form of VCAM-1 on stimulated endothelial cells, seven-domain VCAM
      (VCAM-7D), is a functionally bivalent molecule. One binding site requires the
      first and the other requires the homologous immunoglobulin-like domain. Rotary
      shadowing and electron microscopy of recombinant soluble VCAM-7D molecules
      suggests that the seven Ig-like domains are extended in a slightly bent linear
      array, rather than compactly folded together. We have systematically mutagenized
      the first domain of VCAM-6D (a monovalent, alternately spliced version mission
      domain 4) by replacing 3-4 amino acids of the VCAM sequence with corresponding
      portions of the related ICAM-1 molecule. Specific amino acids, important for
      binding VLA-4 include aspartate 40 (D40), which corresponds to the acidic ICAM-1
      residue glutamate 34 (E34) previously reported to be essential for binding of
      ICAM-1 to its integrin counter-receptor LFA-1. A small region of VCAM including
      D40, QIDS, can be replaced by the similar ICAM-1 sequence, GIET, without
      affecting function or epitopes, indicating that this region is part of a general
      integrin-binding structure rather than a determinant of binding specificity for a
      particular integrin. The VCAM-1 sequence G65NEH also appears to be involved in
      binding VLA-4.

PMID- 7508944
TI  - Effect of ion composition on the changes in membrane potential induced with
      several stimuli in rat mast cells.
AB  - We studied, in different ionic conditions, the effect of various agents on the
      membrane potential of rat peritoneal mast cells using the fluorescent probe
      bisoxonol. Ouabain and ionophore A23187 lead to a fast depolarization of the
      plasma membrane of mast cells, while compound 48/80 and thapsigargin induced
      membrane hyperpolarization, which was more pronounced in the case of compound
      48/80. When using compound 48/80, the amount of gramicidin necessary to
      depolarize the cells was twice the amount required in resting cells, which
      indicates that compound 48/80 increases considerably the activity of the Na+/K+
      pump. On the other hand, the ionophore A23187 elicited a clear depolarization
      which was oblated in the absence of intracellular calcium. The increase in the
      osmolarity of the medium causes a depolarization in the plasma membrane of mast
      cells. Hypertonicity-stimulated depolarization is inhibited by removing sodium
      and potassium.

PMID- 7508941
TI  - The cytoplasmic domain of P-selectin contains a sorting determinant that mediates
      rapid degradation in lysosomes.
AB  - P-selectin is a cell adhesion molecule required transiently on the surface of
      activated platelets and endothelial cells as a receptor for leukocytes. It is
      stored in secretory granules in platelets, endothelial cells, and transfected
      neuroendocrine cells and is rapidly delivered to the plasma membrane upon
      exocytosis of the secretory granules. It is then rapidly internalized in
      endothelial cells and transfected cells. We find that in transfected
      neuroendocrine PC12 cells, the fraction of P-selectin that is not targeted to
      secretory granules is rapidly degraded. In transfected CHO fibroblasts, which
      lack secretory granules, P-selectin was degraded with a half time of 2.3 h in
      plated cells, while low density lipoprotein receptor (LDL-R) had a half life of 9
      h. In cells cultured in ammonium chloride to inhibit lysosomal proteinases, P
      selectin was protected from degradation and rapidly accumulated in vesicles
      enriched in lgp-B, a resident lysosomal membrane protein. The cytoplasmic domain
      of P-selectin was sufficient to confer rapid turnover on LDL-R. Deletion of 10
      amino acids from the cytoplasmic domain of P-selectin extended the half life to
      9.5 h and abrogated rapid lysosomal targeting in the presence of ammonium
      chloride, implicating this sequence as a necessary element of a novel lysosomal
      targeting signal. The rate limiting step in degradation occurred after
      internalization from the cell surface, indicating that sorting of P-selectin away
      from efficiently recycled proteins occurs in endosomes. We propose that this
      sorting event represents a constitutive equivalent of receptor down regulation,
      and may function to regulate the expression of P-selectin at the surface of
      activated endothelial cells.

PMID- 7508943
TI  - A role for the epidermal growth factor-like domain of P-selectin in ligand
      recognition and cell adhesion.
AB  - The selectin family of adhesion molecules mediates the initial interactions of
      leukocytes with endothelium. The extracellular region of each selectin contains
      an amino-terminal C-type lectin domain, followed by an EGF-like domain and
      multiple short consensus repeat units (SCR). Previous studies have indirectly
      suggested a role for each of the extracellular domains of the selectins in cell
      adhesion. In this study, a panel of chimeric selectins created by exchange of
      domains between L- and P-selectin was used to directly examine the role of the
      extracellular domains in cell adhesion. Exchange of only the lectin domains
      between L- and P-selectin conferred the adhesive and ligand recognition functions
      of the lectin domain of the parent molecule. However, chimeric selectins which
      contained both the lectin domain of L-selectin and the EGF-like domain of P
      selectin exhibited dual ligand-binding specificity. These chimeric proteins
      supported adhesion both to myeloid cells and to high endothelial venules (HEV) of
      lymph nodes and mesenteric venules in vivo. Exchange of the SCR domains had no
      detectable effect on receptor function or specificity. Thus, the EGF-like domain
      of P-selectin may play a direct role in ligand recognition and leukocyte adhesion
      mediated by P-selectin, with the lectin plus EGF-like domains collectively
      forming a functional ligand recognition unit.

PMID- 7508945
TI  - Binding of human immunodeficiency virus type-1 (HIV-1) to partially purified
      membrane vesicles of lymphoblastoid cell line CEM.
AB  - Binding of human immunodeficiency virus type 1 (HIV-1) to membrane of its target
      cells was studied by a quantitative and non-isotopic method called the viral
      membrane trapping method (VMTM). Membranes prepared from the CD4 positive
      lymphoblastoid cell line CEM and adsorbed to a solid support retained the ability
      to bind HIV-1. Similar results were obtained by Western dot blot and ELISA
      modification of VMTM, when membrane fraction was bound to nitrocellulose or
      polystyrene, respectively. In ELISA modification, viral association with 1
      microgram of membranes coated on 96-well microplate was linear within a range of
      3.75 micrograms to 60 micrograms of p24gag protein. The use of anti-CD4 mAbs,
      OKT4A and 13B8.2, identified CD4 molecule as a major HIV-1 binding component of
      membrane fraction. The procedure will allow the study of virus binding to this
      and to other possible additional receptor(s).

PMID- 7508946
TI  - A genomic point mutation in the extracellular domain of the thyrotropin receptor
      in patients with Graves' ophthalmopathy.
AB  - Orbital and pretibial fibroblasts are targets of autoimmune attack in Graves'
      ophthalmopathy (GO) and pretibial dermopathy (PTD). The fibroblast autoantigen
      involved in these peripheral manifestations of Graves' disease and the reason for
      the association of GO and PTD with hyperthyroidism are unknown. RNA encoding the
      full-length extracellular domain of the TSH receptor has been demonstrated in
      orbital and dermal fibroblasts from patients with GO and normal subjects,
      suggesting a possible antigenic link between fibroblasts and thyrocytes. RNA was
      isolated from cultured orbital, pretibial, and abdominal fibroblasts obtained
      from patients with severe GO (n = 22) and normal subjects (n = 5). RNA was
      reverse transcribed, and the resulting cDNA was amplified by the polymerase chain
      reaction, using primers spanning overlapping regions of the entire extracellular
      domain of the TSH receptor. Nucleotide sequence analysis showed an A for C
      substitution in the first position of codon 52 in 2 of the patients, both of whom
      had GO, PTD, and acropachy. Genomic DNA isolated from the 2 affected patients,
      and not from an additional 12 normal subjects, revealed the codon 52 mutation by
      direct sequencing and AciI restriction enzyme digestions. In conclusion, we have
      demonstrated the presence of a genomic point mutation, leading to a threonine for
      proline amino acid shift in the predicted peptide, in the extracellular domain of
      the TSH receptor in two patients with severe GO, PTD, acropachy, and high thyroid
      stimulating immunoglobulin levels. RNA encoding this mutant product was
      demonstrated in the fibroblasts of these patients. We suggest that the TSH
      receptor may be an important fibroblast autoantigen in GO and PTD, and that this
      mutant form of the receptor may have unique immunogenic properties.

PMID- 7508948
TI  - Diagnostic markers of permanent idiopathic growth hormone deficiency.
AB  - Idiopathic GH deficiency is a clinically and biologically heterogeneous
      condition. We have attempted to improve its diagnosis by analysing the status of
      52 patients, aged 0.1 to 17.5 yr, with GH peak responses after 2 pharmacological
      stimulation tests of less than 10 micrograms/L. Group 1 (n = 24) had certain GH
      deficiency because of pituitary stalk interruption syndrome, familial form,
      and/or microphallus and hypoglycemia. Group 2 (n = 13) had transient GH
      deficiency. The diagnosis remained uncertain in group 3 (n = 15). The control
      group (n = 77) had prepubertal idiopathic short stature. Growth failure began
      before 5 yr of age in 88% of group 1, 18% of group 2, and 33% of group 3
      patients. The mean GH peaks and the numbers of patients with GH peaks below 7 or
      7-10 micrograms/L were similar in the three groups. Levels of plasma insulin-like
      growth factor-I (IGF-I) and its binding protein-3 (BP-3) were significantly lower
      in group 1 than in groups 2 and 3 (P < 0.001) or in children with idiopathic
      short stature (P < 0.01). When the results of these two parameters were combined,
      only one patient with certain GH deficiency had normal values, but only one
      severely undernourished young child with transient GH deficiency had values below
      the lower limit for children with idiopathic short stature. The diagnosis for
      group 3 remained uncertain, even after spontaneous pubertal development (n = 4),
      as the GH peak was 4.5-10.7 micrograms/L and plasma IGF-I was normal in three
      cases, and BP-3 was normal in four cases. We conclude that certain GH deficiency
      is distinguished from transient GH deficiency by age at onset and plasma IGF-I
      and BP-3 levels. Many patients diagnosed as GH deficient had normal for age
      plasma IGF-I and BP-3 levels, indicating transient GH deficiency in many of them.

PMID- 7508947
TI  - Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in
      cyst fluids of epithelial ovarian cancer.
AB  - Expression of insulin-like growth factor-I (IGF-I), its receptor, and IGF-binding
      proteins (IGFBPs) by epithelial ovarian cancer cells and its mitogenic effect on
      these cells in vitro suggest that IGF-I may have a role in the regulation of
      human ovarian cancer. To examine this role in vivo, we explored the IGF-I/IGFBP
      system in sera and cyst fluids of women undergoing surgery for simple and other
      benign cysts (n = 20) and borderline (n = 5) and invasive malignant epithelial
      neoplasms (n = 11). The IGF-I level was significantly higher in cyst fluid from
      invasive malignant compared to cyst fluid in benign neoplasms (16.1 +/- 2.2 vs.
      7.3 +/- 1.2 nmol/L; P = 0.002). Although benign cysts contained almost no IGFBP,
      high IGFBP-2 levels were detected in malignant cysts regardless of histological
      type. Serum IGFBP-2 levels were also higher in women with invasive malignancy
      than in benign controls (1.32 +/- 0.32 vs. 0.53 +/- 0.07 relative units; P =
      0.004). IGFBP-2 was higher in cyst fluids than in the corresponding sera,
      implying local production of this protein. Estradiol was high in fluid from
      invasive malignant cysts of postmenopausal women and correlated with IGF-I in the
      cyst fluid. Levels of IGF-I, IGFBP-2, and estradiol in cyst fluid could
      discriminate between benign and malignant neoplasms, except for the endometrioid
      type tumors (n = 2). Our data support a role for IGF-I in the proliferation of
      ovarian cancer and suggest that IGF-I and estradiol interact in regulating this
      malignancy.

PMID- 7508949
TI  - Anabolic effects of recombinant insulin-like growth factor-I in cachectic
      patients with the acquired immunodeficiency syndrome.
AB  - The loss of lean body mass accompanying acquired immunodeficiency syndrome (AIDS)
      associated cachexia is refractory to current modes of therapy. GH and insulin
      like growth factor-I (IGF-I) stimulate protein accretion, but resistance to GH
      action has been reported in malnutrition and infection. We hypothesized that GH
      resistance occurs in AIDS-associated cachexia, but that treatment with IGF-I
      would be anabolic. A single injection of GH produced a smaller increase in
      circulating IGF-I in 21 patients with AIDS compared to that in 23 age-matched
      controls (141 +/- 15 vs. 194 +/- 15 micrograms/L; P < 0.02), indicating partial
      GH resistance. Ten subjects received either low or high dose iv recombinant IGF-I
      12 h daily for 10 days. Cumulative nitrogen retention was positive for both
      dosage groups (low dose, 15.42 +/- 6.37 g; high dose, 3.62 +/- 4.15 g), but a
      significant increase in daily nitrogen retention occurred only in the low dose
      group on days 2, 4, 5, 6, and 7. Nitrogen balance and protein turnover (estimated
      by [13C]leucine and [15N] glycine kinetics) during the final 3 days of treatment
      were unchanged compared to baseline values, confirming the transient nature of
      the anabolic response. Repeated administration of IGF-I decreased IGF-binding
      protein-3 levels, producing lower intrainfusion levels of IGF-I and limiting its
      therapeutic efficacy. The basal metabolic rate increased with high dose IGF-I and
      may have contributed to the lack of anabolic effect. We conclude that partial GH
      resistance occurs in AIDS-associated cachexia. Treatment with low dose
      recombinant IGF-I produces significant, but transient, nitrogen retention.
      Alternate routes of IGF-I administration or coadministration with GH may prevent
      attenuation of IGF-I action.

PMID- 7508950
TI  - Human follicular fluid contains pro- and C-terminal immunoreactive alpha-inhibin
      precursor proteins.
AB  - The majority of immunoactive inhibin in human follicular fluid (hFF) is devoid of
      pituitary cell bioactivity and is hypothesized to contain alpha-inhibin monomeric
      proteins known to cross-react with an inhibin antiserum (Monash 1989). The aim of
      this study was to define more precisely the nature of these inhibin
      immunoreactive proteins using alpha-inhibin sequence-specific antisera. First, a
      polyclonal antiserum was raised to precursor amino acids 21-35 (PIN-1) and was
      used in a RIA to measure pro-alpha-inhibin-immunoreactive proteins. Western
      blotting was used to confirm these findings. Secondly, the binding epitope of the
      Monash antiserum was defined by peptide analysis to be located within the C
      terminus (precursor amino acids 326-341) of alpha-inhibin, and this assay was
      then used to monitor the presence of C-terminal sequences. Similar levels of pro
      alpha-inhibin immunoreactivity (PIN-1 RIA; N-terminus alpha-inhibin precursor)
      were detected in hFF collected from women with normal menstrual cycles during the
      follicular phase and from multiple follicles from a woman undergoing ovarian
      hyperstimulation during an in vitro fertilization (IVF) protocol. Western
      blotting with the PIN-1 antibody confirmed the presence of immunoreactive
      proteins of 57,000 and 29,000 mol wt in the follicular fluids of both normal
      cycle and IVF follicles. However, ovarian hyperstimulation elevated
      intrafollicular C-terminal immunoreactivity (Monash RIA) compared to that in
      normal cycle hFF. Furthermore, intrafollicular estradiol and progesterone were
      significantly correlated to C-terminal activity in follicles from IVF, but not in
      normal cycles. These data show that 1) both pro- and C-terminal alpha-inhibin
      proteins are secreted into follicular fluids from normal and IVF cycles,
      suggesting that alpha-inhibin precursor proteins may be physiologically relevant
      in the process of folliculogenesis; and 2) IVF and normal cycle follicular fluids
      differ in their production and processing of inhibin.

PMID- 7508951
TI  - Management of the short stature due to pubertal delay in boys.
AB  - Boys with constitutional pubertal delay who present with decreased growth rate
      pose diagnostic and therapeutic problems. Ninety-one boys seen after the age of
      14 yr for height for age less than -2 SD, growth rate less than 5 cm/yr, and
      pubertal delay were evaluated. The GH peak after the arginine-insulin stimulation
      test was less than 10 micrograms/L in 35 of the subjects; these boys differed
      from the 56 others in having a GH peak of 10 micrograms/L or more, their higher
      body mass index (-0.27 +/- 0.2 vs. -0.85 +/- 0.1 score; P < 0.05), and lower
      plasma insulin-like growth factor-I (IGF-I; 1.2 +/- 0.2 vs. 1.8 +/- 0.2 U/mL; P <
      0.05). The GH peak correlated negatively with the body mass index (P < 0.01), but
      not with plasma levels of testosterone and IGF-I or its GH-dependent binding
      protein (BP-3). At a second GH evaluation, performed with testosterone priming
      (21 boys; 100 mg testosterone heptylate/15 days, im; four doses) or without (6
      boys), 23 patients had increased their GH peak to above 10 micrograms/L, and 4
      had not. Three of these were treated with human (h) GH, and a third GH
      evaluation, performed after full pubertal development, showed a normal GH peak.
      The growth rate during the year preceding the GH evaluation was 3.8 +/- 0.1 cm (1
      7 cm). During the year after the GH evaluation, it was 6.8 +/- 0.3 cm in the 32
      patients followed without therapy, 7.3 +/- 0.3 cm in the 25 patients given
      testosterone (25 mg testosterone heptylate/15 days, im), and 7.3 +/- 1.4 cm in
      the 3 treated with hGH. Spontaneous growth during the 2 periods was correlated
      with testicular volume (P < 0.01) and the plasma testosterone level (P < 0.05),
      but not with the GH peak, plasma IGF-I, or BP-3. The final height (n = 49) was 
      1.0 +/- 0.1 SD, below target height (-0.4 +/- 0.1 SD; P < 0.0001). It was similar
      in patients with a GH peak below or equal to or above 10 micrograms/L and in
      those given or not given testosterone therapy. We conclude that the growth rate
      of boys with constitutional pubertal delay depends on the testicular volume and
      plasma testosterone level, but not on the GH peak, plasma IGF-I, or BP-3 levels.
      Final height is not altered by a transient drop in GH or by low dose testosterone
      therapy.

PMID- 7508952
TI  - Urine hCG beta-subunit core fragment, a sensitive test for ectopic pregnancy.
AB  - hCG is a glycoprotein hormone composed of 2 dissimilar subunits, alpha and beta,
      joined non-covalently. hCG and its free beta-subunit are the principal hCG beta
      immunoreactivities in pregnancy serum samples, and the same plus beta-core
      fragment (beta-subunit residues 6-40 disulfide-linked to residues 55-92) in urine
      samples. Ectopic or tubal pregnancy is difficult to diagnose in emergency rooms.
      With the objective of finding better hCG-related assays for differentiating tubal
      and normal pregnancies, we tested 2 hCG, 1 free beta-subunit and 2 beta-core
      fragment immunoassays. Twelve urine samples were collected in the emergency room
      from women later shown by surgery to have tubal pregnancy. All were 38 to 80 days
      since last period. A further 36 urine samples were collected from the same period
      from those with normal intrauterine pregnancies. Using the 2 hCG assays the
      median level in tubal pregnancy samples was 1/38th and 1/48th of normal pregnancy
      concentrations. With the free beta-subunit assay tubal pregnancy levels were
      1/28th of normal levels. Using 2 beta-core fragment assays (Ciba-Triton UGP kit
      and B204-FBT11 scavenger test), however, tubal levels were most different from
      intrauterine pregnancy, 1/149th and 1/800th of normal levels. A cut-off level of
      100 micrograms/L was considered for the B204-FBT11 beta-core fragment test, at
      which a predictive value of > 98% was suggested for ectopic pregnancy. In an
      additional patient, levels were measured 15 days prior to the diagnosis of tubal
      pregnancy. At this time, results from the 2 hCG tests were 1/97th and 1/126th,
      from the free beta-subunit test was 1/8th and the 2 beta-core assays were 1/413th
      and 1/240th of median normal intrauterine pregnancy levels. While hCG levels are
      reduced in tubal pregnancy, beta-core fragment are reduced much further. beta
      core fragment measurements may offer a major improvement over hCG in diagnosing
      tubal pregnancy in the Emergency Room, and in screening for this life threatening
      disease.

PMID- 7508954
TI  - Comparison of Ziehl-Neelsen staining and immunohistochemistry for the detection
      of Mycobacterium bovis in bovine and caprine tuberculous lesions.
AB  - The avidin-biotin complex peroxidase (ABC-P) method was used to detect
      Mycobacterium bovis, and the results were compared with those obtained by the
      Ziehl-Neelsen (ZN) technique. Lesions were examined from 18 cows and 24 goats
      with tuberculosis. All animals showed pulmonary lesions, which in the cattle were
      mainly minor (i.e. primary complex) but in the goats were sometimes minor and
      sometimes severe. Microscopically, typical granulomas were seen in the lungs and
      lymph nodes, with central necrosis and the cellular components of chronic
      inflammation, but mycobacteria were either seen in small numbers or were not
      detectable. The ABC-P technique was more sensitive than the ZN method, as shown
      by the number of positive animals detected, the intensity of staining, and the
      successful use of low magnification. Caprine lesions, although more severe than
      bovine lesions, appeared to contain fewer organisms.

PMID- 7508953
TI  - Expression of insulin-like growth factor binding protein-4 and -5 mRNAs in adult
      rat forebrain.
AB  - Accumulating evidence indicates that the insulin-like growth factors (IGFs) can
      act as neurotrophic factors. A family of at least six IGF binding proteins
      (IGFBPs) has been characterized. The IGFBPs prolong the half-life of IGFs in
      plasma and may modulate IGF action in a cell- or tissue-specific fashion. Two
      recently characterized IGFBPs, IGFBP-4 and -5, have been shown by northern blot
      hybridization to be expressed in rat brain, but their cellular sites of synthesis
      are poorly characterized. Because IGFBP-4 and IGFBP-5 could potentially modulate
      IGF actions in the brain, we used in situ hybridization histochemistry and 35S
      labeled IGFBP-4 and IGFBP-5 riboprobes to localize sites of IGFBP-4 and -5 mRNA
      expression in adult rat brain. The two IGFBP mRNAs are abundantly expressed
      within discrete regions of brain. The expression patterns of the two genes are
      largely nonoverlapping. Notably, IGFBP-4 mRNA is highly expressed within
      hippocampal and cortical areas, whereas IGFBP-5 mRNA is not detected above
      background in these areas. Within the hippocampus, abundant IGFBP-4 mRNA
      expression is detected in pyramidal neurons of the subfields of Ammon's horn and
      the subiculum and in the granule cell layer of the anterior hippocampal
      continuation. In the cortex, IGFBP-4 mRNA is widely expressed in most areas and
      layers. In contrast, IGFBP-5, but not IGFBP-4, mRNA is detected within thalamic
      nuclei, leptomeninges, and perivascular sheaths. The distinct expression patterns
      of IGFBP-4 and -5 mRNAs within the brain suggest that these IGFBPs may modulate
      paracrine/autocrine actions of the IGFs in discrete brain regions or
      compartmentalization of the IGFs within the brain.

PMID- 7508955
TI  - Quantification of chicken alpha-fetoprotein: a useful tool in studies of embryo
      development and pathology.
AB  - Chicken alpha-fetoprotein (AFP) from the plasma of 12-day-old chick embryos was
      purified by electroelution from SDS/PAGE gels, and used to produce polyclonal and
      monoclonal antibodies. Both reagents were then used to design a sandwich-type
      enzyme-immunoassay for the quantification of AFP in biological fluids. The assay
      was used to quantify AFP in the serum and amniotic fluid of chick embryos with
      abnormalities of the neural tube. Serum AFP was significantly greater in these
      embryos than in normal ones of similar age. Moreover, substantial amounts of AFP
      were demonstrated in the amniotic fluid, whereas this protein was undetectable in
      the amniotic fluid of normal embryos. This method of assay may provide a reliable
      tool for studies of chick embryogenesis and abnormalities of embryonal
      differentiation.

PMID- 7508956
TI  - The histopathological features of canine keratinizing ameloblastoma.
AB  - This paper describes the microscopical features of one variant of canine
      ameloblastoma. It is composed of islands and strands of odontogenic epithelium
      that have infiltrated through the surrounding stroma. Most of the basal cells are
      hyperchromatic, cuboidal and perpendicular to the basement membrane (palisading);
      in some areas their nuclei are located at the distal ends of the cells (reverse
      polarization) and their cytoplasm is vacuolated. These are the classical
      characteristics of the basal cell layer of ameloblastomas. The central cells of
      these tumours are closely-packed, spindle-shaped and exhibit cellular
      keratinization and calcification as prominent features. Amyloid is present
      between the neoplastic epithelial cells in some examples.

PMID- 7508957
TI  - The role of insulin, growth hormone and IGF-I as anabolic agents in the
      critically ill.

PMID- 7508958
TI  - Segmental restriction and target specificity of bullfrog preganglionic neurons
      that exhibit galanin-like immunoreactivity.
AB  - These experiments were designed to examine the distribution of galanin-like
      peptide immunoreactivity (GAL-IR) in bullfrog sympathetic preganglionic neurons
      and to identify the peripheral target organs affected by these neurons. Cells
      expressing GAL-IR were observed in the intermediolateral column of segments 7 and
      8 only. Apparent GAL-IR innervation is present, but rare, in sympathetic chain
      ganglia. Double-labelling with retrogradely transported fast blue and galanin
      antiserum demonstrated that most GAL-IR neurons project via splanchnic nerves to
      innervate the adrenal gland, which receives a dense plexus of GAL-IR fibers
      surrounding chromaffin cells. The adrenal gland is also innervated by
      preganglionic neurons in segments 5 and 6 that do not express GAL-IR. Because
      nitric oxide is expressed in sympathoadrenal preganglionic neurons in mammals
      (Anderson, C.R., Neurosci. Lett., 139 (1992) 280), we examined whether it is
      expressed in bullfrog preganglionic neurons. Nicotinamide adenine dinucleotide
      phosphate-diaphorase positive neurons are present in bullfrog spinal grey at
      segments 5 through 8. These neurons were not double-labelled with fast blue
      retrogradely transported from the sympathetic chain, celiac ganglion, or adrenal
      gland; nor were they double-labelled with GAL-antiserum. Thus nitric oxide is
      apparently not expressed in bullfrog sympathetic preganglionic neurons.

PMID- 7508959
TI  - Differential projections to the raphe nuclei from the medial parabrachial
      Kolliker-Fuse (NPBM-KF) nuclear complex and the retrofacial nucleus in cats:
      retrograde WGA-HRP tracing.
AB  - After injection of wheat germ agglutinin-conjugated horseradish peroxidase (WGA
      HRP, 2 x 30 nl) [corrected] into the nucleus raphe magnus (NRM) of 6 cats, a
      number of retrogradely labelled neurons were observed in the rostral pons, mainly
      in the pontine pneumotaxic area, i.e., the medial parabrachial and Kolliker-Fuse
      (NPBM-KF) nuclear complex, and the tegmental field. In addition, a cluster of
      labelled cells was observed in the retrofacial nucleus (RFN) and its adjacent
      areas in the medulla. Control injections of the same volume of WGA-HRP into the
      medullary magnocellular tegmental field (2 mm lateral to the NRM) resulted in a
      much lower number of labelled neurons in the areas described above, and the
      labelled cells in the tegmental fields were predominant ipsilateral to the
      injected side. Injections into the nucleus raphe pallidus caudal to the NRM
      resulted in a diffuse distribution of labelled neurons, mainly in the tegmental
      fields of the pons and medulla. This study demonstrates that the NRM receives
      specific convergent projections from the NPBM-KF complex and the RFN in the
      medulla. It is suggested that these pathways are involved in the control of
      respiration.

PMID- 7508960
TI  - Stimulation of hair growth by topical application of FK506, a potent
      immunosuppressive agent.
AB  - FK506, a macrolide antibiotic produced by Streptomyces tsukubaensis, is known as
      a potent T cell-specific immunosuppressant, and is effective against graft
      rejection after organ transplantation. Topical application of FK506 (0.03-1
      mumol) to dorsal skin of CD-1 mice stimulated hair growth in a dose-dependent
      manner. Unlike topical application, oral administration of 30 mg/kg of FK506, a
      dose that induces marked immunosuppression, did not stimulate significant hair
      growth. Topical application of FK506 also stimulated hair growth of rats and
      Syrian golden hamsters. FK506 stimulated hair growth even in SCID mice that lack
      both B- and T-cell immunity. Therefore, it is unlikely that the hair growth
      stimulatory effect of FK506 results from its immunosuppressive effect. FK506
      (0.01-1 microM) stimulated both [3H]thymidine and [3H]glycine uptakes to cultured
      mouse vibrissae follicles in a concentration-dependent manner. Moreover, when the
      follicles were treated with FK506 (1 microM) for 16 d, the size of the follicles
      (length of hair plus follicle) increased slightly but significantly. On the other
      hand, the size of the non-treated follicles did not increase significantly. These
      results indicate that FK506 directly stimulates hair follicles. Long-term
      treatment of mice with FK506, i.e., topical application of 1 mumol FK506 twice a
      week for 6 months, did not affect body weight gain of mice, and the FK506-treated
      mice looked healthy. FK506 may be useful as a stimulant of hair growth.

PMID- 7508961
TI  - The large type II 70-kDa keratin of mouse epidermis is the ortholog of human
      keratin K2e.
AB  - The basic keratin pattern of mammalian epidermis consists of the basal keratin
      pair K5/K14 and the differentiation-specific keratin pair K1/K10. Distinct skin
      sites of the adult mouse, i.e., ear, sole of the foot, and interscale regions of
      tail skin, express an additional, type II 70-kilodalton (kDa) keratin without a
      defined new type I partner in suprabasal epidermal cells. Until now, the question
      whether this large keratin is specific for the mouse (or related small rodents)
      or whether orthologous keratins exist in other species has not yet been answered.
      In the present study, we have determined the full-length amino acid sequence of
      the 70-kDa keratin. The keratin comprises 707 amino acid residues and has a
      calculated molecular weight of 70,976.70 Da. From the structural point of view,
      the 70-kDa keratin is remarkable in that more than half of both the V1 and V2
      subdomains of its non alpha-helical head and tail portions consist of different
      glycine-rich peptide motifs that are configured consecutively at least two times
      and as much as seven times in tandem. By means of sequence comparisons and
      phylogenetic investigations, we show that the 70-kDa keratin represents the
      murine ortholog of the human 65-kDa keratin K2e, whose nature as a genuine
      keratin has recently been demonstrated. The unusually large size difference of 5
      kDa between MK2e and HK2e is due mainly to a different duplication rate of the
      glycine-rich peptide motifs in the respective V subdomains of the orthologous
      keratins. We discuss the properties of these highly specialized keratins, which
      in both species define locally restricted epidermal keratin phenotypes, and
      compare them with other orthologous keratins that belong to the basic epidermal
      keratin pattern.

PMID- 7508962
TI  - Characterization of a hair (wool) keratin intermediate filament gene domain.
AB  - In epithelial differentiation keratin intermediate filament genes are expressed
      in multifarious tissue-specific and stage-specific patterns. Pairs of type I and
      type II intermediate filament genes, belonging to multigene families, are
      coordinately regulated, and 4-5 genes of each type are expressed in the hair
      follicle. Accumulating chromosomal mapping data points to a major locus for each
      intermediate filament multigene family on separate chromosomes. In this report we
      describe the isolation of a sheep hair keratin cosmid by chromosome walking that
      overlaps two previously described cosmids and establishes a continuous 100-kb
      segment of cloned DNA containing three hair and three hair-like type II
      intermediate filament keratin genes. A new hair keratin type II intermediate
      filament gene, KRT2.11, is located in the middle of the cluster, and partial
      sequence data reveal a striking conservation of its predicted N-terminal region
      with other sheep hair keratin type II intermediate filament proteins. Expression
      analyses demonstrate the presence of a 2.4-kb KRT2.11 transcript in wool follicle
      RNA and show that expression occurs in the follicle cortical keratinocytes above
      the dermal papilla. The three hair genes are clustered within about 40 kb and
      flanked by hair-like genes that are not expressed in the hair follicle, thereby
      demarcating a hair keratin gene domain.

PMID- 7508963
TI  - Dietary cysteine regulates the levels of mRNAs encoding a family of cysteine-rich
      proteins of wool.
AB  - The abomasal or intravenous infusion of sulphur-containing amino acids such as
      cysteine or methionine into sheep on low-quality diets increases the sulphur
      content of the wool by increasing the synthesis of proteins containing a cysteine
      content of approximately 30 mol %. To investigate the molecular and cellular
      basis of this nutritional effect, quantitative analyses of wool keratin mRNA and
      protein levels, and follicle cortical cell type, were undertaken in sheep
      intravenously infused with cysteine. Northern blot analyses revealed that the
      mRNA levels of one gene family encoding cysteine-rich keratin-associated proteins
      (KAP4 family) expressed in the wool follicle cortex, increased approximately 5-6
      times. Furthermore, the response was rapid as the mRNA levels increased
      approximately 3.5 times after 1 d of the cysteine infusion and, by 1 d post
      infusion, they had fallen, approaching their basal level. No changes in the mRNA
      levels encoding the intermediate filament or the other keratin-associated protein
      families of lower cysteine content were observed. Concomitantly, two-dimensional
      polyacrylamide gel electrophoresis analysis of wool proteins showed a striking
      increase in the abundance of a group of cysteine-rich keratin-associated proteins
      in the wool by the end of the infusion period, returning to basal levels by 3
      weeks later. At the cellular level, KAP4 expression was localized to the follicle
      paracortical cells, and the proportion of paracortical cells and the extent of
      KAP4 expression paralleled the changes in the cysteine infusion status of the
      sheep.

PMID- 7508964
TI  - Human eccrine sweat contains tissue kallikrein and kininase II.
AB  - We attempted to determine the level of sweat kallikrein (kininogenase) and to
      purify and characterize it using sweat collected over a white petrolatum barrier.
      Thermally induced eccrine sweat obtained from 24 healthy subjects showed
      kallikrein activity of 24.4 ng kinins generated/1 mg of sweat protein when heated
      plasma was used as the substrate and 16.1 ng kinin when purified low molecular
      weight bovine kininogen was used as the substrate. Sweat was sequentially
      purified by Sephacryl S-200, diethyaminoethyl Sephacel, and fast flow liquid
      chromatography Mono Q chromatography. Sweat kallikrein had a M(r) of 40,000 and
      was inhibited by aprotinin but not by soybean trypsin inhibitor. The peptide
      generated by sweat kallikrein was identified as lys-bradykinin using reverse
      phase high-performance liquid chromatography and by its amino acid sequence. Anti
      human urinary kallikrein immunoglobulin G neutralized the sweat kallikrein
      activity completely, indicating that the sweat kallikrein is the glandular type.
      Purified sweat and salivary kallikrein showed similar M(r) and responses to
      inhibitors and antibodies. Using immunohistochemistry, kallikrein activity was
      localized in luminal ductal cells and in the peripheral rim of secretory coil
      segments, presumably the outer membrane of the myoepithelium. We also observed
      kininase activity in sweat at M(r) 160,000, which was inhibited by
      ethylenediamine tetraacetic acid, captopril, and angiotensin converting enzyme
      inhibitor peptide, indicating that it is kininase II (or angiotensin converting
      enzyme). Sweat also contains abundant non-kallikrein hydrolases for S-2266 and S
      2302. The demonstration of glandular kallikrein, its tissue localization, and the
      presence of kininase II in sweat provide the basis for future studies on the
      physiologic role of the kallikrein/kinin system in the eccrine sweat gland.

PMID- 7508965
TI  - Immunohistochemical localization of a novel beta 1 integrin in normal and
      pathologic squamous epithelia.
AB  - The 10.1.2 MoAb reacts with a novel alpha chain that associates with the beta 1
      integrin chain and is widely distributed among epithelial and endothelial cells
      of human adult and fetal tissues. In the epidermis and in other squamous
      epithelia, alpha 10.1.2 chains are expressed exclusively in the basal cell layer.
      Here we describe the immunohistochemical localization of alpha 10.1.2 in human
      epidermis, in other squamous epithelia, as well as in cultured keratinocytes.
      alpha 10.1.2 chain localization has also been investigated in a variety of non
      neoplastic and neoplastic lesions of the skin, the uterine cervix, and the lung.
      We show that alpha 10.1.2 chains retain their basal keratinocyte localization in
      hyperplastic skin diseases and in benign tumors of the epidermis and that they
      are strongly expressed in basal cell carcinomas. In contrast, alpha 10.1.2
      expression is decreased in keratinocytes that differentiate in vitro and is lost
      in epidermal dysplastic conditions, in the invading front of squamous cell
      carcinomas of the epidermis, in microinvasive cervical cancers, and in well
      differentiated squamous lung tumors. These findings indicate that alpha 10.1.2
      beta 1 integrin is downregulated during keratinocyte differentiation in vitro and
      in vivo. Moreover, lack of alpha 10.1.2 expression in basal cells of squamous
      epithelia is associated with early dysplastic changes and with the acquisition of
      invasive capacity.

PMID- 7508966
TI  - Human parainfluenza virus type 1 evolution combines cocirculation of strains and
      development of geographically restricted lineages.
AB  - The hemagglutinin neuraminidase (HN) glycoprotein of human parainfluenza virus
      type 1 (HPIV-1) mediates attachment to the host cell and is the target of
      protective antibody. Since the efficacy of a potential vaccine depends on
      antigenic constancy, the antigenic and genetic stability of the HPIV-1 HN
      glycoprotein was examined for 13 isolates obtained between 1981 and 1989.
      Antigenic analysis with a panel of 11 monoclonal antibodies demonstrated a single
      change among 3 isolates from 1989 that distinguished them from all other
      isolates. The HN genes from all 13 isolates and 13 previously published HN gene
      sequences shared > 95% homology. Evolutionary analysis demonstrated cocirculation
      of strains, without a dominant lineage. The 1989 isolates and the previously
      proposed subtype A isolates occupied distinct evolutionary branches, indicating
      geographically limited evolution. The slow rate of evolution and HN homogeneity
      may allow development of a single vaccine formulation for the prevention of
      disease.

PMID- 7508967
TI  - Heat-shock proteins expressed on the surface of human T cell leukemia virus type
      I-infected cell lines induce autoantibodies in rabbits.
AB  - Eight human T cell leukemia virus type I (HTLV-I)-infected cell lines were
      derived in vitro from peripheral blood mononuclear cells of 8 rabbits. Each
      rabbit was then inoculated with its own HTLV-I-transformed cells, after which all
      but 1 rabbit had anti-heat-shock protein (hsp) antibodies in sera. Cell line
      RH/K34, which failed to raise a response to hsp70, caused lethal leukemia when >
      2 x 10(8) live cells were injected into unrelated outbred rabbits. Rabbits
      injected with cell-free virus isolated from RH/K34 cells produced anti-hsp70
      antibodies and became infected but developed no fatal disease. ELISA inhibition
      and flow cytometry analyses indicated that hsp molecules are expressed on the
      surface of RH/K34 and RH/K30, a nonlethal HTLV-I cell line used for comparison;
      surface hsp expression does not occur normally. Two proteins of approximately 72
      and 93 kDa were detected by Western blot in extracts of RH/K30 cells. Presence of
      anti-hsp70 antibodies correlated with resistance to lethal doses of live RH/K34
      cells, suggesting that hsp immunity may influence the outcome of RH/K34
      pathogenicity.

PMID- 7508968
TI  - Inhibition of nitric oxide synthase in experimental gram-negative sepsis.
AB  - Nitric oxide (NO) has been proposed as a mediator of hypotension in septic shock.
      The aim of this study was to determine whether an inhibitor of NO production, NG
      monomethyl-L-arginine (L-NMMA), was able to protect against death in two murine
      models of experimental gram-negative sepsis. L-NMMA (3-300 mg kg-1) did not
      improve survival in intravenous or intraperitoneal models of sepsis. Seven h
      after intravenous infection, L-NMMA (100 mg/kg-1) reduced serum nitrite plus
      nitrate levels (NO breakdown products) from 774 microM in control-treated animals
      to 282 microM in L-NMMA-treated animals (P < .001). This compared to a level of
      103 microM in uninfected mice. L-NMMA produced little change in bacterial load
      following infection and did not increase hepatic damage, as measured by serum
      levels of ornithine carbamoyltransferase. Thus, while L-NMMA may reverse the
      hyporesponsiveness of peripheral circulation in sepsis, it was unable to prevent
      death in these models of gram-negative septic shock.

PMID- 7508971
TI  - Differential sensitivity of rat cardiac sarcolemma and mitochondria to damage
      induced by lipid peroxidation.
AB  - It is well known that the sarcolemma is the organelle most susceptible to lipid
      peroxidative attack in the isolated membrane preparations. To determine whether
      this also occurs in the intact heart, we studied the effect of cumene
      hydroperoxide, an agent capable of initiating lipid peroxidation, on the
      ultrastructure and lanthanum (La) staining of isolated rat hearts perfused with
      HEPES buffer (pH 7.4) containing: 140 mM NaCl, 5 mM KCl, 1 mM MgCl2, 3 mM HEPES,
      1.5 mM CaCl2 and 11 mM glucose. No ultrastructural alterations or intracellular
      deposits of La were observed in myocytes of rats perfused with HEPES buffer.
      Perfusion with cumene hydroperoxide (0.5 mM) for 30 min induced a release of
      malondialdehyde-like substance in the perfusate and a spectrum of myocardial
      ultrastructural alterations. La was always observed only outside the sarcolemma
      in myocytes with moderate damage consisting of clearing of the mitochondrial
      matrix and slight margination of chromatin in the nuclei. Intracellular La was
      found in myocytes with severe and irreversible damages consisting of
      fragmentation of cristae and electron-dense amorphous particles in mitochondria.
      La was deposited on the outer surface of the mitochondrial membranes, lipid
      droplets and myofilaments. These data suggest that mitochondria are more
      susceptible than is the sarcolemma to lipid peroxidation induced by cumene
      hydroperoxide in the beating rat heart.

PMID- 7508970
TI  - Heterosexual transmission of human immunodeficiency virus type 1 variants
      associated with zidovudine resistance.
AB  - During zidovudine therapy, human immunodeficiency virus type 1 (HIV-1) acquires a
      distinctive set of mutations that diminish the sensitivity of the virus to this
      drug in vitro. An AIDS patient is described who, while being treated with
      zidovudine, transmitted HIV-1 bearing a drug resistance mutation to a young woman
      who had never received zidovudine treatment. DNA sequencing of HIV-1 proviruses
      confirmed that these 2 persons shared HIV genetic variants, including a mutation
      at codon 70 in the reverse transcriptase gene associated with reduced in vitro
      sensitivity to zidovudine. This mutation persisted in the woman > 1 year in the
      absence of antiretroviral therapy. HIV-1 with genetic markers of zidovudine
      resistance can be transmitted heterosexually, but it is uncertain whether
      dissemination of drug-resistant virus will substantially reduce the usefulness of
      this drug.

PMID- 7508969
TI  - Sequence variation within the immunodominant epitope-coding region from the
      external glycoprotein of human T lymphotropic virus type II in isolates from
      Seminole Indians.
AB  - Western blot analysis of 16 serum specimens from Seminole Indians demonstrated
      that 14 reacted with the type-specific recombinant epitope (rgp46II+) of human T
      lymphotropic virus type II (HTLV-II), whereas the remaining 2 specimens did not
      (rgp46II-). Both rgp46II- specimens demonstrated presence of HTLV-II genome by
      polymerase chain reaction analysis. Culture of 1 of these specimens demonstrated
      presence of type C retrovirus particles by electron microscopy, and p24gag
      antigens were detectable in culture supernatant. Nucleotide sequence analysis of
      557 bp in the env gene (position 5405-5961) from 2 each of the rgp46II- and
      rgp46II+ specimens demonstrated sequence conservation in the rgp46II epitope (K
      55(162-205)). Thus, lack of immune reactivity to rgp46 is not due to sequence
      variation within this epitope. This observation suggests that immunodominant env
      epitopes may not be universally recognized. Therefore, specimens with p24gag and
      r21eenv reactivity in modified Western blot assays should be further tested by
      more sensitive techniques.

PMID- 7508973
TI  - Hepatitis C virus infection as a risk factor for non-alcoholic liver cirrhosis in
      Taiwan.
AB  - To assess whether hepatitis C virus infection was a risk factor for the
      development of non-alcoholic liver cirrhosis, antibody to hepatitis C virus (anti
      HCV; detected by a second generation HCV enzyme immunoassay), hepatitis B surface
      antigen (HBsAg; detected by radioimmunoassay) were tested in 150 cirrhotics and
      150 sex-matched and age-matched healthy controls. The prevalence of anti-HCV and
      HBsAg in cirrhotics was higher than in controls (22.0%, 73.3% vs. 2%, 18.7%; P =
      0.001). The prevalence of anti-HCV in HBsAg-negative cirrhotics (45.0%) was
      higher than that in HBsAg-positive patients (13.6%; P = 0.001). Both the anti-HCV
      and carriage of HBsAg were associated significantly with liver cirrhosis, showing
      odds ratio of 12.0 for HBsAg carriers and 13.8 for patients with anti-HCV.
      Compared with those without HBsAg and anti-HCV, there was a significantly
      positive linear trend for developing cirrhosis with the presence of HBsAg alone
      (odds ratio = 19.9), anti-HCV alone (odds ratio = 49.0), and those positive for
      HBsAg and anti-HCV (odds ratio = 81.8) (P = 0.00001). The population-attributable
      risk for developing liver cirrhosis was estimated as 10.8% for anti-HCV alone,
      55.2% for HBsAg alone, and 9.4% for both anti-HCV and HBsAg in southern Taiwan.
      In conclusion, this study shows that hepatitis B and C virus infection act
      independently and synergistically in the development of non-alcoholic liver
      cirrhosis among Chinese in Taiwan.

PMID- 7508972
TI  - Markers of hepatitis C virus infection in Sardinian blood donors: relationship
      with alanine aminotransferase levels.
AB  - Serum samples from 1,765 consecutive Sardinian blood donors, negative for
      hepatitis B surface antigen (HBsAg) and for antibodies to human immunodeficiency
      virus (HIV) (anti-HIV), were evaluated for the presence of antibodies to
      hepatitis C virus (anti-HCV) by second-generation ELISA. Anti-HCV was detected in
      25 (1.45%) of the 1,765 donors examined. Anti-HCV was found in 15 of the 1,690
      (0.9%) donors with normal alanine aminotransferase (ALT) and in 10 of the 75
      (13%) donors with elevated ALT (P < 0.0001). Of the 15 anti-HCV-positive donors
      with normal ALT, only five (33%) were confirmed to be positive by second
      generation RIBA, six (40%) were indeterminate, while four (27%) were RIBA
      negative. HCV RNA, as detected by polymerase chain reaction (PCR) using a set of
      primers from the 5'-noncoding region, was found in six of the 15 (40%) donors
      with normal ALT, including five RIBA positive and one indeterminant. Of the 10
      anti-HCV-positive donors with elevated ALT, all were RIBA positive and eight
      (80%) had detectable HCV RNA. Thus, among ELISA-reactive donors, those with
      elevated ALT had a significantly higher probability of being positive for second
      generation RIBA and HCV RNA compared to those with normal ALT levels (P = 0.028).
      None of the 65 donors with elevated ALT but negative for anti-HCV by ELISA had
      detectable serum HCV RNA, as compared to eight of 10 anti-HCV ELISA-positive
      donors (P < 0.0001). However, although negative for HBsAg, 12 of the 65 (18%) had
      serum HBV DNA by PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508974
TI  - The preceptor--preceptee model for faculty "cross-training".
AB  - In the review of the literature, the author notes several discussions concerning
      collaboration between nursing education and service agencies for updating faculty
      clinical practice. This article addresses the Preceptor-Preceptee model for
      Faculty "Cross-training," including the permission process, method, needs
      analysis, and evaluation. A concluding statement by the author strongly
      recommends the utilization of the faculty practice model to enhance the faculty's
      competence in clinical nursing areas.

PMID- 7508976
TI  - Changes in the hypophysial-gonadal axis during the onset of puberty in young
      bulls.
AB  - The objectives of this study were to determine the extent of changes in
      concentrations of testosterone, growth hormone (GH) and insulin-like growth
      factor I (IGF-I) concentrations in blood plasma and to characterize the
      respective plasma-binding proteins of these two peptides during the onset of
      puberty in male calves. The jugular veins of six male Holstein calves (11-weeks
      old) were catheterized and blood was collected every 3 days (one sample every 30
      min for 8 h). Hormone concentrations in plasma were determined by specific
      radioimmunoassay. After incubation with [125I]IGF-I, IGF-I-binding proteins
      (IGFBPs) were separated by gel filtration; radioactivity was determined in each
      fraction. Western ligand blotting using radiolabelled hormones as ligand was also
      used to characterize the IGF-I- and GH-binding proteins in plasma. Puberty was
      characterized by a rapid (in 1 or 2 days) increase in mean concentrations of
      testosterone in plasma (from 0.5 to > 2 ng ml-1) and a pulsatile release of the
      hormone. During puberty, IGF-I concentrations also increased rapidly in 8-10 days
      from +/- 50 ng ml-1 to > 150 ng ml-1, whereas concentrations of GH in plasma
      remained relatively stable during the experimental period. A significant
      correlation was observed between IGF-I and testosterone concentrations (r = 0.77;
      P < 0.001) throughout the experimental period. Three different IGF-I-binding
      protein fractions with apparent molecular masses of > 200, 150-170 and 45-65 kDa
      were found in plasma using gel filtration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7508977
TI  - Effects of hormones, cyclic AMP analogues and growth factors on steel factor (SF)
      production in mouse Sertoli cell cultures.
AB  - Regulation of steel factor (SF) production in Sertoli cells from postnatal mouse
      testes was studied in a mast cell-Sertoli cell coculture system. Treatment of
      Sertoli cells with dibutyryl cAMP (50-1000 mumol l-1), forskolin (1-25 mmol l-1),
      and cholera toxin (10 micrograms ml-1) increased SF production, whereas FSH and
      theophylline had no significant effect. Furthermore, growth factors and
      testosterone, which would play some roles in spermatogenesis, were also tested,
      but none of these stimulated SF production. The constitutive production of SF
      may, rather, reflect the physiological condition of Sertoli cells in vivo.

PMID- 7508978
TI  - Induction of IL-1 beta, IL-6, TNF-alpha, GM-CSF and G-CSF in human macrophages by
      smooth transparent and smooth opaque colonial variants of Mycobacterium avium.
AB  - Both smooth transparent (SmT) and smooth domed-opaque (SmD) colonial variants
      were obtained from a strain of Mycobacterium avium isolated from a patient with
      AIDS. The two variants showed similar biochemical characteristics but SmT
      bacteria proliferated better than SmD bacteria inside human macrophages and were
      much less capable than the SmD variant of inducing the release of IL-1 beta, IL
      6, TNF-alpha, GM-CSF and G-CSF, after incubation for either 3 or 6 days. As
      cytokines are important extracellular signals for immune cells, the lack of
      induction observed in SmT-infected macrophages may be one of the pathogenic
      mechanisms of M. avium.

PMID- 7508975
TI  - Structure-dependent antitumor activities of novel anthracyclines YM1, YM3, YM4
      and YM6: drug transport properties and effects on biomacromolecule synthesis in
      drug sensitive and resistant leukemia cells.
AB  - The antitumor activities of four novel doxorubicin (DOX) analogues, YM1, YM3, YM4
      and YM6 in relation to their structure and drug transport properties, have been
      investigated in U937 monocytic and CCRF-CEM lymphoid drug sensitive leukemia cell
      lines, as well as in CEM/VLB100, a drug resistant subline displaying high levels
      of P-glycoprotein. Treatment of all cell lines with YM1, 3, 4 and 6 produced a
      dose-dependent decrease in DNA, RNA and protein synthesis as measured by [3H]
      thymidine, [3H]-uridine and [3H]-leucine uptake respectively. YM1 was more
      effective than YM3, YM4 or YM6 against the drug sensitive cells. The antitumor
      effects of all these DOX-analogues on macromolecule synthesis in U937 and CCRF
      CEM cells were lower than that of DOX and epirubicin (EDR). A rapid accumulation
      of the novel anthracyclines was found in all cell lines compared with DOX or EDR.
      However, the maximal accumulation of the DOX-analogues was lower than that of
      EDR. There is a greater efflux from CCRF-CEM sensitive cells and less from
      CEM/VLB100 resistant cells of the DOX-derivatives when compared with EDR and DOX.
      Drug-induced cytotoxicity significantly correlated (P < 0.05) with drug retention
      levels in CCRF-CEM and U937 drug sensitive cells as indicated by an inverse
      correlation curve between anthracycline retention and drug-induced IC50 value. It
      was demonstrated that an increased level of drug retained within the sensitive
      cells would therefore produce a more cytotoxic effect of the drug. However, no
      such correlation was observed in CEM/VLB100 resistant cells. YM3 was shown to
      have an increased antitumor activity against CEM/VLB100 resistant cells compared
      with DOX with a lower resistance factor. These results showed that the antitumor
      effects of four novel DOX-analogues, like DOX or EDR, were associated with
      inhibition of DNA replication, transcription and translation. The finding that
      resistant leukemic cells are more susceptible to the cytotoxic effect of YM3 than
      DOX warrants further investigation to identify the intrinsic mechanism of
      resistance.

PMID- 7508982
TI  - Structural features of a multisubstate cardiac mitoplast anion channel:
      inferences from single channel recording.
AB  - Ion channels from sheep cardiac mitoplast (inverted inner mitochondrial membrane
      vesicle) preparations were incorporated into voltage-clamped planar lipid
      bilayers. A low-conductance anion channel (approximately 40 or approximately 85
      pS in symmetric 300 or 550 mM choline Cl, respectively), characterized by the
      presence of two well-defined substates, at approximately 25 and approximately 50%
      of the fully open level, was studied in detail. The substate behavior was
      consistent with a multibarelled channel containing four functionally coupled
      pores. At negative (cis-trans) membrane potentials, the putative protomers
      appeared to gate with substantial positive cooperativity, accounting for the
      apparent absence of a approximately 75% sublevel. At positive holding potentials,
      allosteric promoter interactions were more complicated, and the channel complex
      could be modeled as a dimer of dimers. The protochannels in one dimer ("dimer A")
      appeared to open independently of each other, and with a relatively high
      probability, while the monomers comprising the second dimer ("dimer B") were
      functionally coupled, could only open if both protomers in dimer A were open, and
      closed as soon as one of the monomers in dimer A shut. The channels also
      displayed Ca(2+)-(and Mg(2+)-) sensitive rectification related to bilayer lipid
      surface charge. By assuming that Ca2+ acted solely by screening surface charge,
      the membrane surface potential profile was used as a "microscopic ruler" to place
      one month of the channel within 10-11 A of the bilayer surface.

PMID- 7508979
TI  - Temperature dependence of embryonic cardiac gap junction conductance and channel
      kinetics.
AB  - We have investigated the effects of temperature on the conductance and voltage
      dependent kinetics of cardiac gap junction channels between pairs of seven-day
      embryonic chick ventricle myocytes over the range of 14-26 degrees C. Records of
      junctional conductance (Gj) and steady-state unit junctional channel activity
      were made using the whole-cell double patch-clamp technique while the bath
      temperature was steadily changed at a rate of about 4 degrees C/min. The decrease
      in Gj upon cooling was biphasic with a distinct break at 21 degrees C. In 12 cell
      pairs, Q10 was 2.2 from 26 to 21 degrees C, while between 21 and 14 degrees C it
      was 6.5. The mean Gj at 22 degrees C (Gj22) was 3.0 +/- 2.1 nS, ranging in
      different preparations from 0.24 to 6.4 nS. At room temperature, embryonic
      cardiac gap junctions contain channels with conductance states near 240, 200,
      160, 120, 80 and 40 pS. In the present study, we demonstrate that cooling
      decreases the frequency of channel openings at all conductance levels, and at
      temperatures below 20 degrees C shifts the prevalence of openings from higher to
      lower conductance states: all 240 pS openings disappear below 20 degrees C; 200
      pS openings are suppressed at 17 degrees C; below 16 degrees C 160 and 120 pS
      events disappear and only 80 and 40 pS states are seen. Temperature also affected
      the voltage-dependent kinetics of the channels. Application of a 6 sec, 80 mV
      voltage step across the junction (Vj80) caused a biexponential decay in
      junctional conductance. Decay was faster at lower temperatures, whereas the rate
      of recovery of Gj after returning to Vj0 was slowed. Cooling reduced the fast
      decay time constant, increased both recovery time constants, and decreased the
      magnitude of Gj decay, thus leaving a 10-16% larger residual conductance
      (Gss/Ginit, +/- 80 mV Vj) at 18 than at 22 degrees C. From these results we
      propose that embryonic chick cardiac gap junctions contain at least two classes
      of channels with different conductances and temperature sensitivities.

PMID- 7508981
TI  - Single anion channels reconstituted from cardiac mitoplasts.
AB  - Ion channels from sheep cardiac mitoplast (inverted inner mitochondrial membrane
      vesicle) preparations were incorporated into voltage-clamped planar lipid
      bilayers. The appearance of anion rather than cation channels could be promoted
      by exposing the bilayers to osmotic gradients formed by Cl- salts of large,
      relatively impermeant, cations at a pH of 8.8. Two distinct activities were
      identified. These comprised a multisubstate anion channel of intermediate
      conductance (approximately 60 pS in 300 vs. 50 mM choline Cl, approximately 100
      pS in symmetric 150 mM KCl), and a lower-conductance anion channel (approximately
      25 or approximately 50 pS in similar conditions), which only displayed two well
      defined substates, at approximately 25 and approximately 50% of the fully open
      state. The larger channels were not simple multiples of the lower-conductance
      channels, but both discriminated poorly, and to a similar extent, between anions
      and cations (PCl-/Pcholine+ approximately 12, PCl-/PK+ approximately 8). The
      lower-conductance channel was only minimally selective between different anions
      (PNO3-(1.0) = PCl- > PBr- > PI- > PSCN-(0.8)), and its conductance failed to
      saturate even in high (> 1.0 M) activities of KCl. The channels were not
      obviously voltage dependent, and they were unaffected by 0.5 mM SITS, H2O2,
      propranolol, quinine or amitriptyline, or by 2 mM ATP, or by variations in pH
      (5.5-8.8). Ca2+ and Mg2+ did not alter single channel activity, but did modify
      single current amplitudes in the lower-conductance channel. This effect, together
      with voltage-dependent substate behavior, is described in the following paper.

PMID- 7508980
TI  - Heptanol-induced decrease in cardiac gap junctional conductance is mediated by a
      decrease in the fluidity of membranous cholesterol-rich domains.
AB  - To assess whether alterations in membrane fluidity of neonatal rat heart cells
      modulate gap junctional conductance (gj), we compared the effects of 2 mM 1
      heptanol and 20 microM 2-(methoxy-ethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)
      octanoate (A2C) in a combined fluorescence anisotropy and electrophysiological
      study. Both substances decreased fluorescence steady-state anisotropy (rss), as
      assessed with the fluorescent probe 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5
      hexatriene (TMA-DPH) by 9.6 +/- 1.1% (mean +/- SEM, n = 5) and 9.8 +/- 0.6% (n =
      5), respectively, i.e., both substances increased bulk membrane fluidity. Double
      whole-cell voltage-clamp experiments showed that 2 mM heptanol uncoupled cell
      pairs completely (n = 6), whereas 20 microM A2C, which increased bulk membrane
      fluidity to the same extent, did not affect coupling at all (n = 5). Since gap
      junction channels are embedded in relatively cholesterol-rich domains of the
      membrane, we specifically assessed the fluidity of the cholesterol-rich domains
      with dehydroergosterol (DHE). Using DHE, heptanol increased rss by 14.9 +/- 3.0%
      (n = 5), i.e., decreased cholesterol domain fluidity, whereas A2C had no effect
      on rss (-0.4 +/- 6.7%, n = 5). Following an increase of cellular "cholesterol"
      content (by loading the cells with DHE), 2 mM heptanol did not uncouple cell
      pairs completely: gj decreased by 80 +/- 20% (range 41-95%, n = 5). The decrease
      in gj was most probably due to a decrease in the open probability of the gap
      junction channels, because the unitary conductances of the channels were not
      changed nor was the number of channels comprising the gap junction. The
      sensitivity of nonjunctional membrane channels to heptanol was unaltered in
      cholesterol-enriched myocytes. These results indicate that the fluidity of
      cholesterol-rich domains is of importance to gap junctional coupling, and that
      heptanol decreases gj by decreasing the fluidity of cholesterol-rich domains,
      rather than by increasing the bulk membrane fluidity.

PMID- 7508984
TI  - A single 2'-hydroxyl group converts B-DNA to A-DNA. Crystal structure of the DNA
      RNA chimeric decamer duplex d(CCGGC)r(G)d(CCGG) with a novel intermolecular G-C
      base-paired quadruplet.
AB  - We have found that the introduction of a single 2'-hydroxyl group on the sugar
      phosphate backbone of the B-DNA decamer d(CCGGCGCCGG) transforms it to A-DNA.
      Thus, for the first time the X-ray structures of the same sequence have been
      observed in both the A and B-DNA conformations, permitting a comparison. Crystals
      of the DNA-RNA chimeric decamer d(CCGGC)r(G)d(CCGG) belong to the orthorhombic
      space group P2(1)2(1)2(1) with unit cell dimensions a = 25.63 A, b = 45.24 A and
      c = 47.99 A, and one decamer duplex in the asymmetric unit. The structure was
      solved by a rigid body search using the coordinates of the isomorphous structure
      d(CCCGGCCGGG) and refined to an R value of 0.136 using 2753 unique reflections at
      1.9 A resolution. The final model contains 406 nucleotide atoms and 61 water
      molecules. The chimeric duplex exhibits typical A-DNA geometry, with all the
      sugars in the C(3')-endo puckering and the base-pairs inclined and displaced from
      the helix axis. The 2'-hydroxyl groups on rG6 and rG16 protrude into the minor
      groove surface and form different types of hydrogen bonds; that on strand 1 forms
      an intermolecular hydrogen bond with the furanose ring O(4') of a symmetry
      related C1 residue, while that on strand 2 is involved in two water bridges.
      Crystal packing forces the G4-G17 base-pair in the top half of the duplex to
      slide significantly into the minor groove compared to the corresponding G7-G14
      base-pair in the bottom half, resulting in these base-pairs exhibiting different
      base stacking and intermolecular interactions. The base G4 of the G4-G17 base
      pair forms an unorthodox base "triple", G4*(G10-C11), hydrogen-bonding through
      its minor groove sites N(2) and N(3) to the minor groove atoms N(2) and O(2) of
      both bases of the G10-C11 base-pair of a symmetry-related molecule. The base G10
      of this triple in turn forms a second similar unorthodox base triple,
      G10*(G3*C18), with the adjacent base-pair G3-C18 of the duplex, thus G10 is
      involved in a double triple. On the other hand, in the bottom half of the duplex,
      the C7-G14 base-pair is involved only in a single similar unorthodox base triple
      with G20, (C7-G14)*G20, while the adjacent base-pair rG6-C15 is involved in a
      novel quadruple with C1-G20, (rG6-C15) *(C1-G20), where the latter base-pairs are
      hydrogen-bonded to each other via the minor groove sites
      G(N(2))...C(O(2)).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7508985
TI  - Visualization of a tertiary structural domain of the Tetrahymena group I intron
      by electron microscopy.
AB  - The P4-P6 domain RNA of the group I intron of Tetrahymena thermophila has
      previously been shown by chemical probing to be an independently folding domain
      of the intron's tertiary structure. To directly visualize this tertiary
      structure, the P4-P6 domain and two folding defective mutants were prepared for
      high-resolution electron microscopy using tungsten shadowcasting. In the presence
      of Mg2+, the P4-P6 domain predominantly consists of compact molecules, while the
      two mutant RNAs are nearly all rod-like molecules. The measured length of the rod
      like molecules is 64 (+/- 6) bp, which agrees closely with the length expected
      for molecules containing secondary structure only. In the absence of Mg2+, the P4
      P6 domain contains threefold or tenfold fewer compact structures (depending on
      the mounting procedures) than in the presence of Mg2+. These results provide
      direct evidence for the overall shape of the tertiary structure proposed on the
      basis of biochemical experiment, and they confirm the Mg2+ dependence of tertiary
      folding. An equilibrium between the extended (rod-like) and the compact
      structures is suggested, with the concentration of bound Mg2+ and different
      mounting methods influencing the direction of the equilibrium. The entire group I
      ribozyme (L-21 Sca I RNA) was also examined by electron microscopy in the
      presence of Mg2+, and was revealed to have a compact shape. These studies present
      a direct demonstration of long-range interactions in a catalytic RNA molecule.

PMID- 7508986
TI  - An Escherichia coli RNA polymerase defective in transcription due to its
      overproduction of abortive initiation products.
AB  - One of the potential regulatory steps in procaryotic transcription is promoter
      clearance, a transition step in transcription initiation at which an RNA
      polymerase (RNAP) switches from the initial transcribing stage to the elongation
      stage. The biological significance of promoter clearance and the role of RNAP in
      this process are not understood. One approach to address these questions is to
      study mutant RNAPs that have altered promoter clearance. Because the antibiotic
      rifampicin inhibits transcription by preventing an initial transcribing complex
      from entering the elongation mode, mutant RNAPs which confer rifampicin (Rifr)
      are likely to be altered in promoter clearance. To test this hypothesis, we
      studied the effects of Rifr RNAPs on the pyrBI promoter, which is subject to
      control of promoter clearance in response to the availability of UTP. Two Rifr
      alleles that carry a different altered amino acid residue at position 529 of the
      beta subunit appeared to be defective in transcription from the pyrBI promoter in
      vivo. Biochemical analysis of one of these mutant RNAPs, RpoB3401 with a R529C
      change in the beta subunit, showed that it overproduces aborted initiation
      products from the pyrBI promoter and thus is defective in promoter clearance
      leading to reduced productive initiation. The severity of overproducing the
      aborted initiation products is an inverse function of the UTP concentration
      indicating that RpoB3401 has reduced affinity for UTP and thus is subject to a
      high Km barrier during promoter clearance. The defect of RpoB3401 in abortive
      initiation in vitro could account fully for its reduced initiation activity in
      vivo demonstrating the biological significance of abortive synthesis in
      transcription initiation. Our results indicate that at least part of the "rif
      region" is important for the process of abortive initiation and that promoter
      clearance can be regulated in part by modulating the Km of RNAP for nucleotides
      during initiation. The mutant enzyme is not altered in stuttering RNA synthesis
      at the pyrBI promoter, previously observed with wild-type RNAP. Our results also
      show that the mechanisms underlying the two non-productive initiation events
      (abortive synthesis and stuttering synthesis) at the pyrBI promoter are distinct.

PMID- 7508987
TI  - Formation of a hydrophobic cluster in denatured bovine pancreatic trypsin
      inhibitor.
AB  - Bovine pancreatic trypsin inhibitor (BPTI) unfolds upon reduction of its three
      disulfide bonds. A recombinant model of the reduced state of BPTI, called [R]Ala,
      in which all six Cys residues are replaced with Ala, has been expressed in
      Escherichia coli. 1H nuclear magnetic resonance spectroscopy shows that [R]Ala
      does not contain stable secondary structure. Some chemical shift dispersion
      exists, however, suggesting the existence of non-random interactions in [R]Ala.
      In particular, the side-chain protons of Ile19 resonate upfield of those of
      Ile18. This observation was investigated using an eight residue peptide model,
      P17-24, corresponding to residues 17 to 24 of BPTI. The non-random chemical shift
      dispersion of the Ile residues observed in [R]Ala also occurs in P17-24,
      indicating that P17-24 contains interactions that are similar to those found in
      the corresponding region of [R]Ala. The only interresidue nuclear Overhauser
      effects observed in P17-24 are between the ring protons of Tyr21 and the gamma
      CH3 group of Ile19, indicating that these protons are in close proximity.
      Substitution of Tyr21 by Ala in P17-24 results in the loss of the chemical shift
      dispersion of the Ile resonances, suggesting that the upfield shifts of the Ile19
      resonances are due to ring current shifts arising from the proximity of Tyr21.
      Collectively, these results suggest that the side-chain of Ile19 is positioned at
      least some of the time above the plane of the aromatic ring of Tyr21. We conclude
      that these two residues participate in a hydrophobic cluster in P17-24 and in the
      denatured state of BPTI.

PMID- 7508988
TI  - High concentrations of ppGpp decrease the RNA chain growth rate. Implications for
      protein synthesis and translational fidelity during amino acid starvation in
      Escherichia coli.
AB  - We show that the RNA chain growth rate on lacZ is reduced by an elevated ppGpp
      level even in the absence of starvation. Under these conditions the polypeptide
      chain elongation rate is affected little, if at all. These results lead us to re
      examine the role of ppGpp in the reduction of protein synthesis and translational
      fidelity during amino acid starvation. We find that ppGpp has little or no direct
      effect on translation rate or fidelity. Rather, the effects of ppGpp on
      translation are indirectly caused by the fact that ppGpp inhibits mRNA synthesis,
      making mRNA limiting for translation during amino acid starvation. The reduced
      level of mRNA thereby reduces the severity of the aminoacyl-tRNA limitation and,
      in turn, decreases mistranslation. Mistranslation in the starved relA strain
      therefore results from an increased severity of aminoacyl-tRNA limitation due to
      the failure of this strain to reduce mRNA levels by increasing the level of
      ppGpp. Finally, the initial rise of the ppGpp level in the starved stringent
      strain, followed by a characteristic reduction to a steady poststarved level, can
      now be explained by the initially high, and then decreasing number of "hungry"
      codons adjusted through the mRNA pool.

PMID- 7508989
TI  - Studies on primer binding of HIV-1 reverse transcriptase using a fluorescent
      probe.
AB  - The fluorescent nucleotide analog, 2',3'-trinitrophenyladenosine-5'-triphosphate
      (TNP-ATP), was utilized to quantify the affinities of human immunodeficiency
      virus-1 reverse transcriptase (HIV-1 RT) for its substrates. Interaction of this
      probe with the enzyme brings about a twofold increase in the magnitude of
      fluorescence emission from the probe, and a blue-shift in wavelength maximum,
      from 561 to 553 nm. TNP-ATP binds HIV-1 RT with a dissociation constant of 21
      microM. The presence of millimolar levels of deoxynucleoside triphosphates or
      micromolar levels of an oligonucleotide primer analogue, p(dT)12-18, suppressed
      this enhancement of fluorescence. The fact that inhibition was achieved with much
      lower levels of primer than of dNTPs suggests that TNP-ATP is a probe for the
      binding site of primer on the enzyme, rather than that of deoxynucleoside
      triphosphate. In support of this, the effect of TNP-ATP on the kinetics of DNA
      synthesis catalyzed by the enzyme indicated that the probe is a competitive
      inhibitor with respect to template-primer. The ability of primers and primer
      analogs to reverse the fluorescence enhancement was determined, and the
      corresponding affinities of these compounds for reverse transcriptase were
      calculated. The affinity increased with primer length, increasing more than 50
      fold from a span of 5 to 15 nucleotide residues. The interaction of
      polydeoxynucleotides was consistent with a model in which the enzyme bound at
      adjacent internal sites of about 15 residues in length. Several mammalian and
      bacterial transfer RNA primers were tested, including the natural primer,
      tRNA(3Lys). The affinities were found to be between 0.55 and 1.2 microM, with no
      obvious selectivity for the natural primer, which had a Kd of 0.79 microM. These
      results are discussed within the context of data for HIV-1 RT obtained by other
      methodologies.

PMID- 7508990
TI  - Translational and rotational diffusion of proteins.
AB  - We have investigated the translational and rotational diffusion of two proteins,
      bovine pancreatic trypsin inhibitor and hen egg white lysozyme, using molecular
      dynamics simulations in explicit solvent. The translational diffusion constants
      obtained from the simulations compare favourably with results from experiments.
      However, rotational diffusion constants indicate increased rotational diffusion
      compared to experiments. Further analysis, using simple hydration models,
      suggests that the observed rotational diffusion can be explained without invoking
      a fixed shell of hydration water associated with the protein. Within the
      assumptions of the hydration models, the results suggest that the strength of
      protein-water interactions in the current force field may be slightly
      underestimated.

PMID- 7508991
TI  - Structural characterization of the FK506 binding protein unfolded in urea and
      guanidine hydrochloride.
AB  - Characterizing the structure properties of unfolded proteins is important for
      understanding the stability and folding of native proteins. However, little
      structural information is available for the unfolded state. Using recently
      developed heteronuclear multi-dimensional NMR techniques, the 1H, 13C and 15N
      chemical shift assignments of the FK506 binding protein (FKBP) unfolded in
      concentrated urea and guanidine hydrochloride (GuHCl) solutions have been
      obtained, and the structural properties of unfolded FKBP have been characterized.
      FKBP displays extensive conformational averaging when unfolded in urea and GuHCl,
      but defined regions of secondary structure are present. Subtle differences
      regarding the location and stability of the secondary structures exist between
      the two solvents. Secondary structure formation in unfolded FKPB was correlated
      with statistical and thermodynamic predictions of helix formation as well as with
      the three-dimensional structure of folded FKBP determined by NMR and X-ray
      crystallography. Residues involved in secondary structures in unfolded FKBP are
      generally found in the same type of secondary structure in the folded protein. An
      exception to this was found at the C terminus of FKBP, which forms a different
      secondary structure in the unfolded and folded states.

PMID- 7508983
TI  - Functional architecture of the nicotinic acetylcholine receptor: a prototype of
      ligand-gated ion channels.

PMID- 7508992
TI  - A monoclonal antibody that blocks poliovirus attachment recognizes the lymphocyte
      homing receptor CD44.
AB  - A monoclonal antibody, AF3, was previously shown to specifically inhibit
      poliovirus binding to HeLa cells and to detect a 100-kDa glycoprotein only in
      cell lines and tissues permissive for poliovirus infection. These results
      suggested that the 100-kDa protein may be involved in the pathogenesis of
      poliomyelitis and the cellular function of the poliovirus receptor site. To study
      further the role of the 100-kDa protein in poliovirus attachment, immunoaffinity
      purification, amino acid sequencing, and cDNA cloning were undertaken. The
      results demonstrate that antibody AF3 reacts with the lymphocyte homing receptor
      CD44, a multifunctional cell surface glycoprotein involved in the homing of
      circulating lymphocytes to lymph nodes and the modulation of lymphocyte adhesion
      and activation. Antibody AF3 reacts with a subset of CD44 molecules (AF3CD44H),
      which appears to be a small fraction of the heterogeneously glycosylated CD44
      molecules expressed on hematopoietic and nonhematopoietic cells. Anti-CD44
      monoclonal antibodies, previously reported to induce CD44-mediated modulation of
      lymphocyte activation and adhesion, compete with 125I-AF3 in binding assays,
      demonstrating functional overlap among the epitopes. The anti-CD44 monoclonal
      antibody A3D8, which binds to a greater molecular weight range of CD44 than does
      AF3, inhibits poliovirus binding to a similar degree. CD44 does not act as a
      poliovirus receptor, since CD44-expressing mouse L-cell transformants did not
      bind poliovirus. The poliovirus receptor and AF3CD44H may be noncovalently
      associated, or they may interact through the cytoskeleton or signal transduction
      pathways.

PMID- 7508993
TI  - Nucleocapsid-glycoprotein interactions required for assembly of alphaviruses.
AB  - We have studied interactions between nucleocapsids and glycoproteins required for
      budding of alphaviruses, using Ross River virus-Sindbis virus chimeras in which
      the nucleocapsid protein is derived from one virus and the envelope glycoproteins
      are derived from the second virus. A virus containing the Ross River virus genome
      in which the capsid protein had been replaced with that from Sindbis virus was
      almost nonviable. Nucleocapsids formed in normal numbers in the infected cell,
      but very little virus was released from the cell. There are 11 amino acid
      differences between Ross River virus and Sindbis virus in their 33-residue E2
      cytoplasmic domains. Site-specific mutagenesis was used to change 9 of these 11
      amino acids in the chimera from the Ross River virus to the Sindbis virus
      sequence in an attempt to adapt the E2 of the chimera to the nucleocapsid. The
      resulting mutant chimera grew 4 orders of magnitude better than the parental
      chimeric virus. This finding provides direct evidence for a sequence-specific
      interaction between the nucleocapsid and the E2 cytoplasmic domain during virus
      budding. The mutated chimeric virus readily gave rise to large-plaque variants
      that grew almost as well as Ross River virus, suggesting that additional single
      amino acid substitutions in the structural proteins can further enhance the
      interactions between the disparate capsid and the glycoproteins. Unexpectedly,
      change of E2 residue 394 from lysine (Ross River virus) to glutamic acid (Sindbis
      virus) was deleterious for the chimera, suggesting that in addition to its role
      in nucleocapsid-E2 interactions, the N-terminal part of the E2 cytoplasmic domain
      may be involved in glycoprotein-glycoprotein interactions required to assemble
      the glycoprotein spikes. The reciprocal chimera, Sindbis virus containing the
      Ross River virus capsid, also grew poorly. Suppressor mutations arose readily in
      this chimera, producing a virus that grew moderately well and that formed larger
      plaques.

PMID- 7508994
TI  - Giardiavirus-resistant Giardia lamblia lacks a virus receptor on the cell
      membrane surface.
AB  - Giardia lamblia virus (GLV) is a small nonenveloped double-stranded RNA virus
      that infects specifically the parasitic protozoan G. lamblia. Among the many
      collected strains of G. lamblia, a few turn out to be highly resistant to the
      virus infection. Two of these strains, Ac and JH, were subjected to
      electroporation with the RNA from GLV-infected G. lamblia WB strain. Subsequent
      studies indicated the presence of GLV double-stranded RNA and GLV protein in the
      electroporated and propagated cells. Virus particles, released by the transfected
      cells into the culture medium, were capable of infecting the virus-sensitive G.
      lamblia WB strain. When the WB cells were incubated with GLV at 4 degrees C and
      treated with the bifunctional cross-linking reagent disuccinimidyl suberate,
      little GLV protein was detectable inside the cells by immunofluorescent staining.
      However, patches of fluorescent granules were found on the membrane surface of
      the cells, suggesting cross-linking of the viruses with a certain membrane
      component(s). Similar treatment of the resistant strains Ac and JH showed no
      fluorescence either inside or outside of the cells. Two other closely related
      parasitic protozoa, Tritrichomonas foetus and Trichomonas vaginalis, cannot be
      infected by GLV via either viral infection or RNA transfection. The [35S]cysteine
      labeled protein profiles in Triton X-114 extracts of G. lamblia WB, Ac, and JH
      were compared. The profile of the WB strain differs clearly from that of Ac and
      JH. It remains to be seen, however, whether this difference is related at all to
      the different susceptibilities to GLV infection.

PMID- 7508995
TI  - Influenza virus NS1 protein stimulates translation of the M1 protein.
AB  - The influenza virus NS1 protein was shown to stimulate translation of the M1
      protein. M-CAT RNA, which contains the chloramphenicol acetyltransferase (CAT)
      reporter gene and the terminal noncoding sequence of segment 7 (coding for the M1
      and M2 proteins), was ribonucleoprotein transfected into clone 76 cells
      expressing the influenza virus RNA polymerase and NP proteins required for the
      transcription and replication of influenza virus ribonucleoproteins. When the
      cells were superinfected with a recombinant vaccinia virus which expresses the
      NS1 protein, CAT expression from the M-CAT RNA was significantly stimulated but
      transcription was not altered. The expression of NS-CAT RNA, which contains
      noncoding sequences of segment 8 (coding for the NS1 and NS2 proteins), was not
      altered by the NS1 protein. Site-directed mutagenesis showed that the sequence
      GGUAGAUA upstream of the initiation codon on segment 7 was required for
      stimulation.

PMID- 7508996
TI  - Antigenic determinants of measles virus hemagglutinin associated with
      neurovirulence.
AB  - The biological activity of monoclonal antibodies specific for the hemagglutinin
      protein of measles virus strain CAM recognizing six epitope groups according to
      their binding properties to measles virus strain CAM/R401 was investigated in
      vivo in our rat model of measles encephalitis. When injected intraperitoneally
      into measles virus-infected suckling rats, some monoclonal antibodies modified
      the disease process and prevented the necrotizing encephalopathy seen in
      untreated animals. The analysis of measles virus brain isolates revealed
      emergence of variants that resisted neutralization with the passively transferred
      selecting monoclonal antibody but not with other monoclonal antibodies.
      Monoclonal antibody escape mutants were also isolated in vitro, and their
      neurovirulence varied in the animal model. Sequence data from the hemagglutinin
      gene of measles virus localize a major antigenic surface determinant of the
      hemagglutinin protein between amino acid residues 368 and 396, which may be
      functionally important for neurovirulence. The data indicate that the interaction
      of antibodies with the measles virus H protein plays an important role in the
      selection of neurovirulent variants. These variants have biological properties
      different from those of the parent CAM virus.

PMID- 7508997
TI  - Influenza A virus M2 ion channel protein: a structure-function analysis.
AB  - A structure-function analysis of the influenza A virus M2 ion channel protein was
      performed. The M2 protein of human influenza virus A/Udorn/72 and mutants
      containing changes on one face of the putative alpha helix of the M2
      transmembrane (TM) domain, several of which lead to amantadine resistance when
      found in virus, were expressed in oocytes of Xenopus laevis. The membrane
      currents of oocytes expressing mutant M2 ion channels were measured at both
      normal and low pH, and the amantadine-resistant mutant containing the change of
      alanine at residue 30 to threonine was found to have a significantly attenuated
      low pH activation response. The specific activity of the channel current of the
      amantadine-resistant mutants was investigated by measuring the membrane current
      of individual oocytes followed by quantification of the amount of M2 protein
      expressed in these single oocytes by immunoblotting analysis. The data indicate
      that changing residues on this face of the putative alpha helix of the M2 TM
      domain alters properties of the M2 ion channel. Some of the M2 proteins
      containing changes in the TM domain were found to be modified by addition of an N
      linked carbohydrate chain at an asparagine residue that is membrane proximal and
      which is not modified in the wild-type M2 protein. These N-linked carbohydrate
      chains were further modified by addition of polylactosaminoglycan. A glycosylated
      M2 mutant protein (M2 + V, A30T) exhibited an ion channel activity with a voltage
      activated, time-dependent kinetic component. Prevention of carbohydrate addition
      did not affect the altered channel activity. The ability of the M2 protein to
      tolerate deletions in the TM domain was examined by expressing three mutants
      (del29-31, del28-31, and del27-31) containing deletions of three, four, and five
      residues in the TM domain. No ion channel activity was detected from expression
      of M2 del29-31 and del27-31, whereas expression of M2 del28-31 resulted in an ion
      channel activity that was activated by hyperpolarization (and not low pH) and was
      resistant to amantadine block. Examination of the oligomeric form of M2 del28-31
      indicated that the oligomer is different from wild-type M2, and the data were
      consistent with M2 del28-31 forming a pentamer.

PMID- 7508998
TI  - Characterization of T-helper epitopes of the glycoprotein of vesicular stomatitis
      virus.
AB  - The T-helper (Th) cell epitopes in the glycoprotein (GP) of vesicular stomatitis
      virus serotype Indiana (VSV-IND) were analyzed with a complete panel of
      overlapping synthetic peptides. Three Th-cell epitopes in C57BL/6 (H-2b) mice and
      two epitopes in BALB/c (H-2d) mice were defined by their ability to stimulate in
      vitro proliferation of virus-primed, CD8+ T-cell-depleted spleen cells in a class
      II-restricted manner. A series of CD4+, I-Ab-restricted T-cell hybridomas from
      VSV-primed C57BL/6 mice were characterized by their production of interleukin-2
      and interleukin-3 upon stimulation with VSV-IND or purified VSV GP in vitro. Of
      nine hybridomas derived from three independent fusions, five were specific for
      amino acids (aa) 415 to 433 (p8) of VSV-IND GP, three recognized aa 52 to 71
      (p41), and one reacted against aa 316 to 335 (p17). Fluorocytometric analysis of
      Th hybridomas or VSV-stimulated T-cell lines with monoclonal antibodies specific
      for the T-cell receptor V beta chain did not reveal obvious correlations between
      the T-cell receptor V beta gene segment used and the epitope recognized. All
      three peptides recognized by H-2b mice and both epitopes recognized by H-2d mice
      which were characterized in primed T-cell populations were capable of activating
      specific Th cells in vivo as measured by the induction of antibody class switch
      from immunoglobulin M (IgM) to IgG. Thus, the epitopes are relevant for VSV GP
      specific Th response in vivo and are able to provide functional help for the
      production of anti-VSV-specific neutralizing IgG antibodies.

PMID- 7509000
TI  - Nevirapine resistance mutations of human immunodeficiency virus type 1 selected
      during therapy.
AB  - Drug susceptibility and mutations in the reverse transcriptase (RT) gene were
      analyzed with 167 virus isolates from 38 patients treated with nevirapine, a
      potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) RT.
      Resistant isolates emerged quickly and uniformly in all patients administered
      nevirapine either as monotherapy or in combination with zidovudine (AZT).
      Resistance developed as early as 1 week, indicating rapid turnover of the virus
      population. The development of resistance was associated with the loss of
      antiviral drug activity as measured by CD4 lymphocyte counts and levels of HIV
      p24 antigen and RNA in serum. In addition to mutations at amino acid residues
      103, 106, and 181 that had been identified by selection in cell culture,
      mutations at residues 108, 188, and 190 were also found in the patient isolates.
      Sequences from patient clones documented cocirculating mixtures of populations of
      different mutants. The most common mutation with monotherapy, tyrosine to
      cysteine at residue 181, was prevented from emerging by coadministration of AZT,
      which resulted in the selection of alternative mutations. The observations
      documented that, under selective drug pressure, the circulating virus population
      can change rapidly, and many alternative mutants can emerge, often in complex
      mixtures. The addition of a second RT inhibitor, AZT, significantly altered the
      pattern of mutations in the circulating population of HIV.

PMID- 7508999
TI  - Minimal sequence requirements of a functional human immunodeficiency virus type 1
      primer binding site.
AB  - The initiation of human immunodeficiency virus type 1 (HIV-1) reverse
      transcription occurs by the extension of a tRNA(3Lys) primer bound near the 5'
      end of the genomic RNA at a position termed the primer binding site (PBS). The
      PBS is an 18-nucleotide sequence of the HIV-1 genome which is complementary to
      the 3'-terminal 18 nucleotides of the tRNA(3Lys). To investigate the sequence
      specificity of the interaction between tRNA(3Lys) and the PBS, we have
      constructed proviral genomes containing mutations in the PBS region. A mutant PBS
      was constructed in which the 18 nucleotides complementary to tRNA(3Lys) were
      substituted with 18 nucleotides predicted to be complementary to the 3'-terminal
      bases of a tRNA(Phe) molecule [pHXB2PBS(phe)]. A second proviral genome was
      constructed in which the PBS complementary to tRNA(Phe) was changed such that the
      first six nucleotides correspond to the wild-type PBS [pHXB2PBS(pheC)]. In all
      models of reverse transcription, the complementarity between the minus- and plus
      strand PBS DNA facilitates the template switch and elongation of plus-strand DNA,
      resulting in a complete proviral genome. To test this model, we have inserted a
      five-nucleotide sequence 6 bp 3' of the mutant PBSs, which corresponds to the
      last five nucleotides of the wild-type PBSs [pHXB2PBS(phe+5) and
      pHXB2PBS(pheC+5)]. Transfection of plasmids containing the wild-type or mutant
      proviral genomes into COS-1 cells resulted in similar levels of intracellular
      expression of HIV-1 gag and env gene products as determined by
      immunoprecipitation with sera from AIDS patients and release of virus as
      determined by p24 assay. Transfection of pHXB2PBS(phe) or pHXB2PBS(phe+5) did not
      result in the production of infectious virus, while replication-competent viruses
      from cells transfected with pHXB2PBS(pheC) were detected very infrequently.
      Transfection of pHXB2PBS(pheC+5), however, consistently resulted in the
      production of infectious virus, although the appearance of the virus was delayed
      compared with those from cells transfected with pHXB2(wild type). Reinfection of
      SupT1 cells with equal amounts of p24 antigen resulted in similar kinetics of
      replication. PCR was used to amplify the PBS, and individual DNA products were
      subcloned into M13mp18. Sequence analysis of the PBS region of integrated
      proviruses derived from transfection of pHXB2PBS(pheC+5) revealed that the 18
      nucleotide PBS complementary to tRNA(3Lys) was regenerated with a deletion of 6
      bp 3' to the PBS region in all phage clones examined.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7509001
TI  - Rearrangement of the VP6 gene of a group A rotavirus in combination with a point
      mutation affecting trimer stability.
AB  - A group A rotavirus isolated from a lamb with diarrhea in Qinhai province, China,
      was serially passaged in fetal calf kidney cells. In passage 96, rearrangements
      of RNA segments 5 and 6 of the viral genome were found. Here we report the
      nucleotide and predicted amino acid sequences of normal and rearranged RNA 6,
      coding for the major inner capsid protein VP6. In comparison with the normal gene
      (N6), the rearranged RNA 6 (R6) contained the normal open reading frame followed
      by a 473-nucleotide (nt) duplication of the gene beginning 23 nt after the
      termination codon. The duplicated region starts at nt 768 and runs through to the
      3' end of the gene. In accordance with the nucleotide sequence of the rearranged
      RNA 6, a normal-length VP6 product was found in cells infected with the mutant.
      However, a single-amino-acid change from proline to glutamine at position 309
      slightly affected the electrophoretic mobility of the VP6 monomer of the R6
      mutant and reduced the stability of VP6 trimers on gels and at low pH values
      compared with the normal gene product. The degree of relatedness of VP6 of the
      Chinese lamb rotavirus Lp14 to those of other group A rotaviruses was determined.

PMID- 7509002
TI  - Antigenicity of the N8 influenza A virus neuraminidase: existence of an epitope
      at the subunit interface of the neuraminidase.
AB  - To locate antigenic epitopes on the N8 neuraminidase (NA), we generated a panel
      of 97 monoclonal antibodies (MAbs), 66 of which inhibited NA activity (NI
      antibodies). Three groups of NI MAbs were identified from their different
      reactivities with escape mutants. Group 1 antibodies recognized the peptide loop
      containing residues 344 to 346, which appears to be an immunodominant region on
      the rim of the enzyme center of the N8 NA. Group 2 antibodies recognized a novel
      epitope containing residues 150, 199, 367, 399, and 400 (N2 numbering). From the
      location of these residues on the three-dimensional structure of the N8 NA, the
      epitope appears to be located at the interface of two adjacent monomers in the
      tetrameric NA, one contributing residues 150 and 199 and the other contributing
      residues 367 and 399 to 400. The available evidence indicates that the MAbs of
      this group react with the NA only after it is fully assembled. The third group of
      antibodies recognized the peptide loops containing residues 367 and 399 to 400.
      All of the amino acid substitutions in N8 escape mutants which affect the NI
      activity of antibodies were located in the peptide loops known to form epitopes
      in the N2 and N9 subtypes, indicating that antigenic regions in the NA head
      inducing NI antibodies appear to be similar among different subtypes of influenza
      A viruses. The MAbs used in this study will be valuable in studying the role of
      each N8 NA epitope in host immune defense systems and in the kinetics analysis of
      the biosynthesis of the enzyme.

PMID- 7509003
TI  - Role of oligomerization of the S13 Env-Sea oncoprotein in cell transformation.
AB  - The env-sea oncogene is a fusion of the S13 viral envelope gene, env, and cell
      derived sequences encoding a tyrosine kinase domain, termed sea. The Env-Sea
      oncoprotein is synthesized as a precursor of 155 kDa which undergoes proteolytic
      processing to generate a disulfide-linked complex of the proteins gp85 and gp70.
      We analyzed the oligomeric state of the Env-Sea oncoprotein in S13-transformed
      cells and demonstrate that both gp155 and the gp85-gp70 complex can oligomerize.
      To address the relevance of these oligomers in transformation by S13, a mutant
      that is temperature sensitive for the transformed phenotype was used. The
      tyrosine-phosphorylated oligomers of gp155 were found at the nonpermissive
      temperature, and thus oligomerization per se appears to be insufficient to elicit
      a transformed phenotype. Efficient intracellular transport of gp155 appears to be
      required to generate a tyrosine-phosphorylated oligomer of the gp85-gp70 complex,
      the presence of which correlates with the transformed phenotype. This gp85-gp70
      complex appeared to have a higher level of kinase activity than the other forms
      of the Env-Sea protein. These results suggest that oligomerization, transport,
      and intracellular localization represent levels at which the oncogenic activity
      of the Env-Sea oncoprotein may be regulated.

PMID- 7509004
TI  - Redesignation of the RNase D activity associated with retroviral reverse
      transcriptase as RNase H.
AB  - In the presence of Mn2+, reverse transcriptase of both human immunodeficiency
      virus and murine leukemia virus hydrolyzes duplex RNA. However, designating this
      novel activity RNase D conflicts with Escherichia coli RNase D, which
      participates in tRNA processing. On the basis of its location in the RNase H
      domain, we propose that this novel retroviral activity be redesignated RNase H*.

PMID- 7509005
TI  - Functional role of the zipper motif region of human immunodeficiency virus type 1
      transmembrane protein gp41.
AB  - To study the functional role of the zipper motif region, located in the N
      terminal region of the envelope transmembrane protein of human immunodeficiency
      virus type 1, a series of vaccinia virus-expressed mutant proteins containing a
      proline substitution in this region were characterized. All of the mutant
      proteins showed partial or no inhibition in gp160 cleavage, demonstrated impaired
      ability of gp120 to associate with gp41, and were unable to mediate syncytium
      formation with CD4+ cells. Moreover, mutants 580 and 587 secreted excessive gp120
      into the medium compared with the wild type. Mutations in this region affected
      the conformation of the local or proximal sequence but did not alter the
      conformation conferred by a distal site. These studies reveal the crucial role of
      the C-terminal segment of the zipper motif region in envelope heterodimeric
      association and suggest that this sequence forms a gp120 contact site.

PMID- 7509007
TI  - Alternative splicing in the alpha 5(IV) collagen gene in human kidney and skin
      tissues.
AB  - Type IV collagen is a complex molecule composed of three alpha chains that can be
      of types alpha 1(IV) to alpha 5(IV). Each alpha chain contains an amino-terminal
      collagenous domain and a carboxyl-terminal noncollagenous (NC) domain consisting
      of 229 amino acids, which is involved in intermolecular cross-linking to
      construct the basement membrane network. Specific localization of alpha 5(IV)
      collagen in glomerular basement membranes (GBM) in the kidney indicates its
      crucial role for that construction. In human kidney cortex and skin RNA, we found
      an alternative splicing transcript which skips exon 50 of the alpha 5(IV)
      collagen gene using reverse transcription-polymerase chain reaction and direct
      sequencing of the PCR products. This alternative splicing introduces a stop codon
      at the first codon of exon 51, resulting in an mRNA encoding a protein lacking
      the 84 NC domain carboxylterminal amino acid residues encoded by exons 50 and 51.
      Recently, gene mutations affecting the alpha 5(IV) collagen NC domain have been
      reported in patients with X-linked Alport syndrome who display GBM destruction
      and progressive renal failure, which are usually milder in female patients.
      Therefore, the alternative splicing, if its truncated products are dominantly
      expressed in glomeruli, may cause GBM impairment and renal failure progression.

PMID- 7509006
TI  - [Immunohistochemical study on keratin expression of uterine reserve cells].
AB  - An immunohistochemical expression in the reserve cells of the uterine cervix
      using monoclonal antibodies of cytokeratin which detected the different subtypes
      of keratin was studied. Although the reserve cells were positive for all the four
      cytokeratin antibodies (CAM5.2, M-20, M-888, M-630), different immunoreactivity
      was found as follows: CAM5.2 reacted uniformly and intensely in the cervical
      glands, but weak in the reserve cells. M-20 reacted similar to that of CAM5.2 in
      the cervical glands, but was weaker stained in the reserve cells than with
      CAM5.2. M-888 reacted uniformly and intensely in both the cervical glands and
      reserve cells. M-630 reacted only in the reserve cells, but seldom in the
      cervical glands. Hence, CAM5.2 and M-20, which detected No.8 and No.18 of
      antiserum for low-molecular weight cytokeratin, reacted more weakly in the
      reserve cells than in the cervical glands, and M-630, which detected No.5 and
      No.14 of antiserum for high-molecular weight cytokeratin, reacted uniformly and
      intensely in the reserve cells. That results suggested the reserve cells revealed
      the expression as the stratified squamous epithelium. As for cell proliferation
      on the cervical glands and reserve cells, the positive nuclear staining for
      proliferating cell nuclear antigen (PCNA) was found in both of them, especially
      in the cervical glands just above the reserve cells. Therefore, the reserve cells
      had characteristics of squamous cell epithelium and developed to metaplastic
      cells.

PMID- 7509008
TI  - [Evaluation of a cytokeratin 19 assay kit "BALL ELSA CYFRA21-1"].
AB  - We evaluated "BALL ELSA CYFRA21-1" kit, an immunoradiometric assay kit for
      cytokeratin 19. Monoclonal antibodies KS19-1 and BM19-21 are used for
      immunoadsorbent and indicator, respectively. There was no problems in
      reproducibility, dilution test and recovery test. Minimum detectable
      concentration was 0.42 ng/ml. The antigen measured by this kit was
      immunologically cross-reactive with tissue polypeptide antigen (TPA) and CYFRA21
      1 concentration was closely correlated with TPA concentration in patient's serum.
      One of twenty-six healthy subjects showed serum concentration over a cut-off
      value of 2.0 ng/ml. Serum CYFRA21-1 concentration elevated in 5 of 10 esophageal
      cancer patients, 5 of 10 gastric cancer patients, 7 of 10 colorectal cancer
      patients and 6 of 10 pancreatic cancer patients. Positive rate in patients with
      benign disease including hepatopathy was low. BALL ELSA CYFRA21-1 kit is reliable
      and CYFRA21-1 could be a useful tumor marker in gastrointestinal cancer.

PMID- 7509010
TI  - Dexamethasone inhibits nitric oxide synthase mRNA induction by interleukin-1
      alpha and tumor necrosis factor-alpha in vascular smooth muscle cells.
AB  - The effects of interleukin-1 alpha, tumor necrosis factor-alpha and dexamethasone
      on the induction of nitric oxide synthase mRNA in rat aortic smooth muscle cells
      were studied. Neither interleukin-1 alpha (up to 100 U/ml) nor tumor necrosis
      factor-alpha (up to 5000 U/ml) was capable of inducing nitrite/nitrate production
      and nitric oxide synthase mRNA in smooth muscle cells. In contrast, treatment for
      12 hr or longer with a combination of the two synergistically induced
      nitrite/nitrate and cyclic GMP production in cell culture media and nitric oxide
      synthase mRNA, both of which were prevented by dexamethasone. Contamination with
      bacterial lipopolysaccharide, which may affect the induction of nitric oxide
      synthase, was below 30 pg/ml in all experiments. Our findings show that
      dexamethasone and these cytokines regulate the induction of nitric oxide synthase
      at the mRNA level in vascular smooth muscle cells.

PMID- 7509009
TI  - Nitric oxide synthase mRNA in endothelial cells: synergistic induction by
      interferon-gamma, tumor necrosis factor-alpha and lipopolysaccharide and
      inhibition by dexamethasone.
AB  - Regulation of nitric oxide synthase mRNA by interferon-gamma, tumor necrosis
      factor-alpha, bacterial lipopolysaccharide (LPS) and dexamethasone in rat aortic
      endothelial cells was examined. The combination of interferon-gamma (100 U/ml)
      and tumor necrosis factor-alpha (5000 U/ml) evoked a time-dependent increase in
      nitric oxide synthase mRNA and nitrite/nitrate production, both of which were
      inhibited by dexamethasone. Neither interferon-gamma (100 U/ml), tumor necrosis
      factor-alpha (5000 U/ml) nor LPS (100 ng/ml) alone was capable of increasing
      nitric oxide synthase mRNA and nitrite/nitrate production in these cells.
      However, combinations of two of the three agents synergistically increased both
      nitric oxide synthase mRNA and nitrite/nitrate production. When the three agents
      were applied simultaneously, nitric oxide synthase mRNA and nitrite/nitrate
      production were both markedly increased. LPS contamination, which may affect the
      induction of nitric oxide synthase, was below 20 pg/ml in all experiments unless
      LPS was added exogenously, namely, the effects observed were those of the
      cytokines themselves. Our results suggest that in endothelial cells, these
      cytokines regulate the production of nitric oxide at the level of nitric oxide
      synthase mRNA induction.

PMID- 7509012
TI  - [Efficacy of the "Gen-Probe Mycobacterium Tuberculosis Direct Test (MTD)" for
      detection of Mycobacterium tuberculosis in clinical specimens--comparison between
      the MTD and the test by culture on Ogawa's egg medium or in the MB Check System].
AB  - Three or more weeks are usually required for detecting Mycobacterium tuberculosis
      by the known culture methods, and therefore, the development of a rapid
      bacteriological diagnostic method for M. tuberculosis has been urgently awaited.
      Recently, Gen-Probe Inc. has developed the "Gen-Probe Mycobacterium Tuberculosis
      Direct Test (MTD)", which is based on amplification of the ribosomal RNA (rRNA)
      of M. tuberculosis in clinical specimens and hybridization of the amplified rRNA
      with a M. tuberculosis-specific DNA probe, as a rapid direct diagnostic method
      for tuberculosis. We therefore compared the sensitivity and specificity of the
      MTD in detecting M. tuberculosis with the culture methods on Ogawa's egg medium
      and in the MB Check System, using 107 clinical specimens as test material. The
      results obtained are as follows: 1. Of the 61 clinical specimens which were
      negative when cultured on Ogawa's egg medium, 13 (21.3%) were positive for M.
      tuberculosis using the MTD, and of the 48 clinical specimens which were negative
      when cultured in the MB Check System, 8 specimens (16.7%) were positive for M.
      tuberculosis using the MTD. 2. All of the specimens which yielded growth of M.
      tuberculosis (identified by the DNA probe) either on Ogawa's egg medium or in the
      MB Check System, except one, were positive for M. tuberculosis in the MTD. The
      only one exception was a specimen which was positive for M. tuberculosis in both
      Ogawa's medium and the MB Check System.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509013
TI  - The effect of rh-cytokines on the sensitivity of normal human CFU-GM progenitors
      to Ara-C and on the S-phase activity of light density human bone marrow cells.
AB  - This study examines the effect of pre-incubation in liquid phase of normal human
      CFU-GM progenitors with recombinant human (rh) cytokines prior to exposure to
      cytosine arabinoside (Ara-C) in clonogenic culture. Light density marrow cells
      (LMDCs) were preincubated in Biorich (chemically defined serum-free complete
      medium) with G + GM-CSF or IL-3 prior to semi-solid culture with Ara-C (10(-4) M
      10(-12) M). Cell cycle analysis was performed by flow cytometry pre- and post-rh
      cytokine treatment. Data from 26 normal marrows studied clonogenically,
      demonstrated a 60% reduction in CFU-GM with 10(-4) M Ara-C. Preincubation in
      Biorich medium with the addition of G + GM-CSF or IL-3 caused a significant
      enhancement of sensitivity to Ara-C across the dose curve. Biorich medium alone
      had an apparent protective effect resulting in amelioration of the cytotoxic
      effect of Ara-C. Cell cycle analysis of eight subjects showed significant
      recruitment into S-phase following pre-treatment with cytokines. A reduction in S
      phase activity was noted in cells pre-incubated in Biorich alone. In summary, it
      would appear that cytokines can enhance the sensitivity of normal CFU-GM to Ara-C
      in vitro possibly due to an increase in S-phase activity. Pre-incubation in
      nutrient medium without cytokines resulted in cell quiescence.

PMID- 7509014
TI  - Forskolin potentiates G-CSF-induced proliferation of a murine myeloblastic
      leukemia cell line.
AB  - The role of the cAMP/A-kinase signaling pathway in G-CSF dependent proliferation
      of murine myeloblastic NFS-60 cells was investigated. G-CSF treatment resulted in
      a rapid and transient elevation of cAMP content of NFS-60 cells. G-CSF treatment
      of NFS-60 cells also resulted in the activation of A-kinase parallel to the
      increase in cAMP concentration. A low concentration (0.2-10 nM) of forskolin
      augmented the G-CSF-dependent cell proliferation, although forskolin by itself
      had no effect on NFS-60 cell growth. Forskolin did not affect the IL-3-induced
      proliferation of this cell line. Addition of forskolin resulted in further
      increases in the cAMP level, activation of A-kinase in NFS-60 cells stimulated by
      G-CSF. Proliferation of NFS-60 cells by G-CSF, but not by IL-3, was blocked by
      the axial diastereoisomer of adenosine 3',5'-phosphorothioate (Rp-cAMPS), a
      competitive cAMP antagonist. KT-5720(8R*,9S*,11S*)-(-)-9-hydroxy-9-n-hexyloxy-8
      methyl-2, 3, 9, 10-tetrahydro-8, 11-epoxy-1H, 8H, 11H-2,7b, 11a
      triazadibenzo(a,g) cycloocta(c,d,e)trinden-1-one), an A-kinase inhibitor,
      inhibited the G-CSF-dependent proliferation. These findings suggest that
      activation of the cAMP/A-kinase signaling pathway may be involved in G-CSF
      mediated cell proliferation of NFS-60 cells, whereas IL-3-dependent proliferation
      is not mediated in such a manner.

PMID- 7509011
TI  - [Development of hepatocellular carcinoma in the patients with a history of
      tuberculosis].
AB  - Of the patients diagnosed as having hepatocellular carcinoma (HCC) at Chiba
      University Hospital and affiliated hospitals from 1978 to 1992. 191 patients with
      histories of having a blood transfusion more than 10 years ago were studied.
      Histories of having transfusions for tuberculosis were the most common, being
      documented by 50 patients. Of those patients receiving transfusions for
      tuberculosis, the average period from transfusion to the detection of HCC was
      31.1 years and the average year of transfusion was 1955. Liver dysfunction was
      found during routine medical examinations of the most patients (38.9%), and HCC
      was diagnosed in 17% of the patients soon after the detection of liver
      dysfunction. Of the HCC patients with histories of tuberculosis treatment, anti
      hepatitis C virus was frequently tested positive regardless of a history of
      transfusion. Patients with histories of transfusions for tuberculosis should
      continually be examined for liver dysfunction, and it must be considered that
      these patients have a risk of developing HCC.

PMID- 7509015
TI  - Constitutive production of IL-6 in the anemic mice of W/Wv genotype.
AB  - IL-6 was found to be produced by bone marrow cell fraction enriched for
      hemopoietic stem cells in response to IL-3 stimulation. To confirm the production
      of IL-6 by hemopoietic stem cells, we studied the response of W/Wv mouse bone
      marrow cells to IL-3 stimulation in terms of IL-6 production. Genetically anemic
      mice of W/Wv genotype are known to be depleted of normal hemopoietic stem cells.
      Bone marrow cells of W/Wv mice produce IL-6 without IL-3 stimulation. But bone
      marrow cells of the litter mate (+/+) mice studied as controls do not produce IL
      6 without stimulation. IL-3 induced the production of IL-6, GM-CSF and G-CSF from
      the bone marrow cells of +/+ mice. Gene expression of IL-6, GM-CSF, G-CSF and IL
      3 in these mice was detected in total bone marrow cells after IL-3 stimulation.
      In contrast, bone marrow cells of C3H mice did not produce IL-3 even after IL-3
      stimulation. Bone marrow cells of C3H mice reportedly produce a diffusible IL-3
      inhibitor (NIL-3), but those of C57BL mice do not. Present findings indicate the
      strain-dependent differences in hemopoietic stimulating factor production. The
      constitutive IL-6 production in W/Wv mice might be due to a constant and strong
      demand for blood cell production of the anemic mice.

PMID- 7509016
TI  - Acute myeloblastic leukemia (AML-M2) expressing CD19 B-cell lymphoid antigen
      without myeloid surface antigens.

PMID- 7509017
TI  - Computer-assisted reconstruction of axonal arborizations anterogradely labelled
      with the Phaseolus vulgaris leucoagglutinin technique.
AB  - This paper describes a computer-assisted method which allows the tracing of
      axonal arborizations, and the reconstruction in a either grey-scale or a binary
      image representation, of all labelled neuronal processes located within different
      focal planes of a single tissue section. The system includes a Nikon microscope
      connected to a CCD video camera, and a Macintosh microcomputer. Each step of the
      method is described in order to show that the capturing of images, retouching and
      pasting are easily and rapidly performed using commercially available hardware
      and software.

PMID- 7509018
TI  - Short-range differential pulse voltammetry for fast, selective analysis of basal
      levels of cerebral compounds in vivo.
AB  - Differential pulse voltammetry (DPV) with pretreated biosensors (carbon fibre
      microelectrodes (mCFE), 10-30 microns diameter) allows selective in vivo
      measurement of basal endogenous levels of dopamine (DA), serotonin (5-HT), their
      metabolites (dihydroxyphenylacetic acid, DOPAC; 5-hydroxyindoleacetic acid, 5
      HIAA), and neuropeptides. We have now modified DPV in order to reduce the time of
      analysis from tens of seconds to 1-2 s without losing selectivity. We call this
      newly reported method short-range differential pulse voltammetry (SRDPV). Simply,
      while in DPV the complete oxidation peak is recorded, SRDPV measures only the top
      of each oxidation peak. For example, to monitor peak 2 which corresponds to the
      in vivo oxidation of extracellular DOPAC and occurs at approximately +85 +/- 10
      mV, the initial (Ei) and final (Ef) potentials applied with DPV were -100 mV and
      +200 mV, respectively, while they were +75 mV (Ei) and +95 mV (Ef) with SRDPV. At
      the typical scan range of 10 mV.s-1, the effective time of measurement was 30 s
      for DPV and 2 s for SRDPV. A similar procedure was performed to analyze peak 3 (5
      HIAA, occurring at +230 +/- 11 mV) with Ei + 50 mV and Ef + 350 mV for DPV, or
      +220 mV and +240 mV for SRDPV. DPV and SRDPV were compared in vitro by
      quantitating DOPAC and 5-HIAA in solutions of increasing concentrations (chosen
      on the basis of the suggested in vivo content of these two compounds). Data
      indicated that similar sensitivity and selectivity were obtained with both
      methods at all concentrations, supporting the applicability of SRDPV for in vitro
      studies. In vivo experiments were performed in anesthetized adult male rats
      prepared for voltammetry by inserting the electrically pretreated biosensor
      (mCFE) into the striatum. DPV measurements were performed automatically every 3-5
      min and were alternated every 10-20 min with a sequence of 5-10 SRDPV scans
      performed every 10-30 s. Subsequent pharmacological or electrical manipulations
      of the two biogenic amine systems studied were monitored by alternate use of DPV
      and SRDPV. The data presented support the capability of SRDPV with pretreated
      biosensors to measure in vivo electroactive compounds with selectivity and
      sensitivity comparable to that of DPV, but with improved time resolution.

PMID- 7509019
TI  - Effects of the new histamine H2 receptor antagonist, FRG-8813, on gastric mucin
      in rats with or without acidified ethanol-induced gastric damage.
AB  - It is not presently well understood whether the histamine H2 receptor antagonist
      has a function other than the inhibition of gastric acid secretion, such as the
      effect on the gastric mucosal defence mechanism. In this paper, we report the
      effect of FRG-8813 (N-[4-[4-(piperidinylmethyl)pyridyl-2-oxy]-(Z)-2-butenyl]-2-
      (furfurylsulfinyl) acetamide), a new histamine H2 receptor antagonist, on the rat
      gastric mucin content with or without 0.15N HCl-ethanol (60 %)-induced gastric
      damage. The prior administration of FRG-8813 significantly inhibited the
      occurrence of macroscopically observable hemorrhagic lesions induced by the
      acidified ethanol treatment. Using a newly developed biochemical method, the
      mucin content of the deep corpus and antral mucosa of the acidified ethanol
      treated animals was significantly reduced to 50% and 32% of the control,
      respectively. These reductions were inhibited by the pretreatment with FRG-8813.
      Total mucin content in the entire stomach recovered to about 80% of the control
      value after pretreatment with FRG-8813. A single oral administration of FRG-8813
      (30 mg/kg) caused no significant change in the total mucin content, but mucin in
      the adherent mucus gel layer selectively and significantly increased to 250% of
      the control. These results suggest that FRG-8813 not only inhibits acid secretion
      but may also affect the gastric mucosal defensive mechanism as well.

PMID- 7509020
TI  - Gastrin gene expression in human colon cancer cells measured by a simple
      competitive PCR method.
AB  - Gastrin is mitogenic for several colon cancers and is postulated as an autocrine
      growth factor for colon cancer cells. In the present study we report the
      development of a simple competitive polymerase chain reaction (PCR) method for
      measuring relative abundance of gastrin gene expression in colon cancer cells.
      Primers flanking exons 2 and 3 of the gastrin gene were utilized for co
      amplification of cDNA and genomic DNA. The amplification of genomic DNA was
      distinguished from that of cDNA by the presence of the 130 bp intron sequence
      which was resolved by electrophoresis on agarose gels. A standard reaction of
      competitive PCR, using known concentrations of genomic DNA and cDNA, was first
      established. The steady state levels of gastrin mRNA were next quantitated in
      three human colon cancer cell lines (HCT-116, Colo-205 and DLD-1) by competitive
      PCR. Gastrin mRNA levels in these cell lines ranged from approximately 0.1 to 1.0
      fmoles/mg total RNA (approximately 2-25 copies of gastrin mRNA per cell). Thus
      low to moderate levels of gastrin were expressed by human colon cancer cell lines
      which may function as autocrine growth factors for colon cancers.

PMID- 7509022
TI  - Prevalence of antibodies to hepatitis C virus in populations at low and high risk
      for sexually transmitted diseases in Rio de Janeiro.
AB  - In order to investigate the sexual transmission of the Hepatitis C Virus (HCV),
      the prevalence of specific antibodies in populations at high and low risk for
      sexually transmitted diseases (STDs) was evaluated. The population at low risk
      for STDs was composed of persons who voluntarily donated blood at the Hospital
      Universitario Clementino Fraga Filho (HUCFF) between July and November, 1990 (n =
      2494). The population at high risk for STDs was drawn from an ongoing study on
      the natural history of Human Immunodeficiency Virus (HIV) infection (n = 210, 187
      with sexual risk factors for HIV infection). All samples were screened using a
      first generation ELISA. Repeat reactive samples were then tested in a second
      generation RIBA. For all ELISA positive samples, two sex and age-matched ELISA
      negative controls were selected. Data pertaining to the presence of antibodies to
      the Hepatitis B core antigen (anti-HBC antibodies) and to Treponema pallidum were
      abstracted from the medical records. The prevalence of RIBA 2 confirmed HCV
      infection among the blood donors was 2.08%, which is well above the reported
      prevalence in similar populations from developed western countries. Among the HIV
      infected homosexuals, the encountered prevalence was 7.96% (p < 0.0005). For the
      whole group with sexually acquired HIV infection, the prevalence was 8.02% (p <
      0.000005). Anti-HBc antibodies were more frequently present in anti-HCV RIBA-2
      confirmed positive blood donors than in controls (p < 0.001). 33.3% of the HCV
      positive blood donors and 11.04% controls were found to be anti-HBc positive (p <
      0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509021
TI  - Role of beta-adrenoceptors in the expression of morphine withdrawal signs.
AB  - The effects of intracerebroventricular (i.c.v.) pretreatment with the
      noradrenergic neurotoxin DSP-4 and beta 1- and beta 2-adrenoceptor antagonists on
      the expression of morphine withdrawal signs were investigated in mice. Mice were
      chronically treated with morphine (8-45 mg/kg, s.c.). Several withdrawal signs
      were observed following naloxone challenge in morphine-dependent mice which had
      been pretreated with vehicle. Treatment with DSP-4 before the naloxone challenge
      suppressed the expression of morphine withdrawal signs, including jumping and
      "wet dog" shakes. Similarly, pretreatment with the beta 1-antagonist atenolol
      significantly reduced the incidence of naloxone-precipitated jumping and "wet
      dog" shakes. However, pretreatment with the beta 2-antagonist ICI118,551
      suppressed the expression of "wet dog" shakes, but not that of jumping. These
      findings suggest that the central noradrenergic system may mediate the expression
      of withdrawal signs. The blocking effects of beta-antagonists indicate that
      naloxone-precipitated jumping may be mediated predominantly by beta 1
      adrenoceptors, while naloxone-precipitated "wet dog" shakes may be mediated by
      both beta 1- and beta 2-adrenoceptors.

PMID- 7509024
TI  - Evidence for nontargeted mutagenesis in a monkey kidney cell line and analysis of
      its sequence specificity using a shuttle-vector plasmid.
AB  - Intact pZ189 DNA was allowed to replicate in monkey kidney vero cells that had
      been pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The E. coli
      MBM7070 was transfected with replicated plasmid, and those with mutations in the
      supF gene were identified. The frequency of mutants that did not contain
      recognizable changes in the electrophoretic mobility of the plasmid DNA was
      scored. The frequency of such mutants was 12.2 x 10(-4) (43/35376) and 6.2 x 10(
      4) (22/35712) in mutants derived from cells pretreated with 0.2 mumoles/l and 2
      mumoles/l MNNG respectively; these values represent an increase of 5.8- and 2.9
      fold over the spontaneous mutation frequency of 2.1 x 10(-4) (10/47741) (p <
      0.01). Sequence analysis of the supF genes of these mutants showed that 89%
      (24/27) of base substitutions occurred at G.C base pairs; 59% of the base
      substitutions (16/27) were transversions, and 41% (11/27) were transitions. The
      types of base substitutions were predominantly G.C-->T.A and G.C-->A.T. 48% of
      base substitutions occurred at 6 sites of the supF gene; 4 of these sites consist
      of 5'-TTNN where N is G or C. Base substitutions never previously reported were
      found, namely, T-->C at 61, G-->T at 70, G-->T at 99, and G-->C at 103 were
      found; these have never been reported up to now. In addition, 2 of the 5
      frameshifts occurred in the region 99-105 of the supF gene (GGTGGGG), suggesting
      that this region is a hot spot for nontargeted frameshifts. These results
      strongly suggest that nontargeted mutagenesis can occur in mammalian cells and
      shows that the spectrum of mutations induced differs from that of spontaneous and
      targeted mutations.

PMID- 7509025
TI  - Distribution of X-ray-induced G2 chromatid damage among Chinese hamster
      chromosomes: influence of chromatin conformation.
AB  - Exponentially growing primary embryonic Chinese hamster cells, in which the
      pattern of distribution of heterochromatin is well characterized, were X
      irradiated and fixed at 1, 2, 3, and 4 h following irradiation. In one set of
      cells repair of damage was completely blocked by ara A. The frequencies of
      chromatid breaks and exchanges were evaluated for individual chromosomes. An
      analysis of observed and estimated expected frequencies of chromosomal
      aberrations indicated that in general, (a) the initial damage was higher in
      euchromatic regions than the heterochromatic regions and (b) the repair of DNA
      lesions (as evaluated by the frequencies of chromatid gaps and breaks) was more
      efficient in euchromatic regions than heterochromatic regions.

PMID- 7509026
TI  - Cytotoxic and genotoxic effects of five n-alkanals in primary cultures of rat and
      human hepatocytes.
AB  - Five n-alkanals were examined for cytotoxicity, as evaluated by the trypan blue
      exclusion test, and for genotoxicity, as evaluated by the induction of
      unscheduled DNA synthesis (UDS), in primary cultures of rat and human
      hepatocytes. After 20 h exposure, cytotoxicity was similar in cells of the two
      species, and increased with the length of the carbon chain. In rat hepatocytes,
      propanal (10-100 mM), butanal (10-100 mM), pentanal (3-30 mM) and hexanal (3-30
      mM) induced a modest but significant and dose-dependent increase of net nuclear
      grain counts, while in human hepatocytes this effect was not detected. Nonanal (3
      30 mM), which showed the highest cytotoxic effect, failed to induce UDS in both
      cell types. These results seem to suggest that at the concentrations which are
      presumably attained after ingestion with food or generated by lipid peroxidation
      processes the five n-alkanals tested are presumably unable to induce genotoxic
      effects in the human liver.

PMID- 7509023
TI  - Arabidopsis homologs of the shaggy and GSK-3 protein kinases: molecular cloning
      and functional expression in Escherichia coli.
AB  - The conservation in evolution of fundamental signal transduction modules offers a
      means of isolating genes likely to be involved in plant development. We have
      amplified by PCR Arabidopsis cDNA and genomic sequences related to the product of
      the shaggy/zeste-white 3 (sgg) segment polarity gene of Drosophila. This
      regulatory protein is functionally homologous to glycogen synthase kinase-3 in
      mammals (GSK-3), which regulates, among others, the DNA-binding activity of the c
      jun/AP1 transcription factor. Analysis of PCR products led to the identification
      of five genes; for two of which, corresponding full-length cDNAs, ASK-alpha and
      gamma (for Arabidopsis shaggy-related protein kinase), were characterized. The
      encoded proteins were 70% identical to GSK-3 and sgg over the protein kinase
      catalytic domain and, after production in Escherichia coli, autophosphorylated
      mainly on threonine and serine residues, but phosphotyrosine was also detected.
      ASK-alpha and ASK-gamma also phosphorylated phosphatase inhibitor-2 and myelin
      basic protein, on threonine and serine, respectively. The high conservation of
      the protein kinases of GSK-3 family, and their action at the transcriptional
      level, suggest that the ASK proteins have important functions in higher plants.

PMID- 7509027
TI  - 3-isobutyl-1-methylxanthine inhibits the mutagenic activity of 7,12
      dimethylbenz[a]anthracene in epithelial liver cells in culture.
AB  - The mutagenic activity of 7,12-dimethylbenz[a]anthracene in epithelial liver
      cells (CHEL) in culture was unaffected by the enhancement of intracellular cAMP
      induced to different extents and with different mechanisms by forskolin and 3
      isobutyl-1-methylxanthine. However, the latter compound exerted antimutagenic
      effects (> 60%), which may be tentatively ascribed to inhibition of the inducible
      monooxygenase isoform(s) responsible for the specific biotransformation of 7,12
      dimethylbenz[a]anthracene to highly mutagenic metabolites in CHEL cells.

PMID- 7509028
TI  - In vivo cytogenetic analyses of the carbamate pesticides Dithane M-45 and Baygon
      in mice.
AB  - Two carbamate pesticides, Dithane M-45 and Baygon, were analysed for their
      cytogenetic effects using meiotic chromosome analysis and the micronucleus test
      in Swiss albino male mice. The three sub-lethal doses of 1687.5, 3375 and 5962.5
      mg/kg bw of Dithane M-45 and 1250, 2500 and 3750 mg/kg bw of Baygon were employed
      in all the experiments. The results demonstrate that neither Dithane M-45 nor
      Baygon could induce a significant (P > 0.05) increase in the number of
      chromosomal aberrations in the germ cells or in the percentage of micronuclei in
      erythrocytes.

PMID- 7509030
TI  - Evaluation of sister-chromatid exchanges in mouse spermatogonia: a comparison
      between the classical fluorescence plus Giemsa staining and an immunocytochemical
      approach.
AB  - Sister-chromatid exchanges (SCE) were analyzed in mouse spermatogonia using two
      different protocols for bromodeoxyuridine (BrdU) exposure and detection. With the
      classical approach, based on subcutaneous implantation of agar-coated BrdU
      tablets and fluorescence plus Giemsa (FPG) staining a satisfactory
      differentiation of spermatogonial metaphases was obtained with 50 or 25 mg BrdU
      per mouse (two or one tablets respectively). Alternatively, the immunodetection
      of BrdU was carried out after exposure to a very low BrdU concentration (three
      injections i.p., 3 mg/kg b.w. each, at 5-h intervals), and after exposure to one
      BrdU tablet; SCE frequencies evaluated in this way were lower than those found
      after classical FPG staining, even when the mice were exposed to the same BrdU
      concentration (one tablet, 25 mg BrdU). We concluded that the two methodologies
      may have different sensitivities with respect to SCE detection. In addition, when
      the effect of a treatment with mitomycin C was tested (1 mg/kg b.w., at time
      intervals ranging from 24 h to 5 days), no sister-chromatid differentiation was
      obtained with the multiple injection protocol, or with one BrdU tablet. By
      contrast, with two BrdU tablets and FPG, well differentiated metaphases were
      found at any time interval tested after MMC treatment, and the peak frequency of
      SCE (3.4 times the baseline) was observed at 55 h after treatment, as expected on
      the basis of cell cycle duration in spermatogonia. In summary, even though the
      use of medium-low concentrations of BrdU was successful in untreated animals,
      these protocols appeared inadequate to detect SCE induction by MMC. It is
      possible that, in the presence of cell cycle delay induced by the treatment,
      interferences with the rate of BrdU uptake produce an unsatisfactory
      differentiation of sister chromatids.

PMID- 7509029
TI  - Sister-chromatid exchanges in Picea abies--a test for genotoxicity in forest
      trees.
AB  - A genotoxicity test, based on the evaluation of sister-chromatid exchange
      frequencies, has been developed for the spruce fir. The basic frequency was 36.9
      SCEs/cell. Mitomycin C treatment (MMC, 5 x 10(-6) M, 0.5 h) doubled the
      'spontaneous' SCE frequency, maleic hydrazide treatment (MH, 5 x 10(-4) M, 0.5 h)
      increased it nearly 7-fold. This corresponds to data obtained previously for
      Vicia faba. Chromatid-type aberrations were induced by the same mutagens (MH, 5 x
      10(-4) M, 0.5 h; MMC 2 x 10(-5) M, 1 h) or by triethylenemelamine (TEN, 2 x 10(
      4) M, 0.5 h). MH treatment resulted in aberration yields comparable to those
      observed in Vicia faba, MMC and TEM were less efficient aberration inducers in P.
      abies. While SCEs may be counted for single chromosomes, for reliable evaluation
      of chromatid aberrations large numbers of complete and well spread metaphases
      have to be inspected.

PMID- 7509031
TI  - Enhanced clastogenicity of contaminated groundwater following UV irradiation
      detected by the Tradescantia micronucleus assay.
AB  - The Tradescantia micronucleus (Trad-MCN) assay was used to determine clastogenic
      effects of contaminated groundwater collected near a hazardous waste landfill.
      Water samples were taken from a purification plant (activated charcoal
      filtration, UV irradiation) which was built to avoid groundwater contamination by
      this landfill. Five series of experiments were conducted during approximately 4
      months. In addition, water samples were irradiated under laboratory conditions
      with increasing doses of UV light. Several field water samples gave positive,
      dose-dependent effects before filtration and irradiation. Maximal values (6.1 +/-
      4.7 micronuclei (MCN)/100 tetrads) were six-fold above controls. UV irradiation
      of activated charcoal-filtered water resulted in an enhancement of MCN
      frequencies. Exposure of groundwater to UV irradiation in the laboratory led to a
      dose-dependent increase of micronuclei. At the highest dose (1500 J/m2) the MCN
      frequency was more than six times higher than in the unirradiated sample (5.4 +/-
      1.0 vs. 0.8 +/- 0.4 MCN/100 tetrads). The clastogenicity of UV-irradiated samples
      decreased with a half-life of approximately 1 day. Irradiation of tap water did
      not increase the MCN frequency. Our results indicate that irradiation of water
      with UV light for disinfection purposes might lead to a transiently increased
      genotoxicity of chemically polluted water samples.

PMID- 7509032
TI  - Antagonizing effect of triphenyltin chloride on cytosine-1-beta-D
      arabinofuranoside potentiation of chromosome aberrations induced by mitomycin C.
AB  - We previously reported that the organotin triphenyltin chloride (TPTC), which has
      been widely used as an anti-fouling coating for fishing nets and ship bottoms,
      potentiated clastogen-induced chromosome aberrations during the G2 phase of the
      cell cycle. In this communication, CHO cells treated with mitomycin C (MMC) were
      post-treated with TPTC in the presence and absence of other agents--cytosine-1
      beta-D-arabinofuranoside (araC), hydroxyurea, or caffeine--having a similar
      effect during the G2 phase of the cell cycle. The potentiating effect of araC was
      completely inhibited in the presence of TPTC at the concentration at which TPTC
      showed its potentiating effect, suggesting that potentiating effects of TPTC and
      araC are antagonistic. On the other hand, combined treatment with TPTC and
      caffeine or hydroxyurea showed a potentiating effect almost equal to the sum of
      the potentiating effects of each given separately.

PMID- 7509033
TI  - Ectopic pregnancy.

PMID- 7509034
TI  - Expansile stents in esophageal cancer.

PMID- 7509035
TI  - Expansile stents in esophageal cancer.

PMID- 7509036
TI  - RNA. Deviants--or emissaries.

PMID- 7509037
TI  - Transformation by polyoma virus middle T-antigen involves the binding and
      tyrosine phosphorylation of Shc.
AB  - Polyoma virus middle T-antigen converts normal fibroblasts to a fully
      transformed, tumorigenic phenotype. It achieves this, at least in part, by
      binding and activating one of the non-receptor tyrosine kinases, pp60c-src, pp62c
      yes or pp59c-fyn (reviewed in refs 2 and 3). As a result, middle T-antigen itself
      is phosphorylated on tyrosine residues, one of which (Tyr 315) acts as a binding
      site for the SH2 domains of phosphatidylinositol-3'OH kinase 85K subunit. Here we
      show that another tyrosine phosphorylation site in middle T-antigen (Tyr 250;
      refs 4, 5) acts as a binding region for the SH2 domain of the transforming
      protein Shc. This results in Shc also becoming tyrosine-phosphorylated and
      binding to the SH2 domain of Grb2 (ref. 10). This probably stimulates p21ras
      activity through the mammalian homologue of the Drosophila guanine-nucleotide
      exchange factor Sos (reviewed in ref. 11). We suggest that middle T-antigen
      transforms cells by acting as a functional homologue of an activated tyrosine
      kinase-associated growth-factor receptor.

PMID- 7509038
TI  - Trinity of cation channels.

PMID- 7509039
TI  - Gene interactions affecting mechanosensory transduction in Caenorhabditis
      elegans.
AB  - Genetic screening has identified a group of mec (mechanosensory) genes that are
      required for the function of a set of six touch-receptor neurons in the nematode
      Caenorhabditis elegans. Such genes potentially encode components of the
      mechanosensory apparatus. We have cloned one of these genes, mec-10, which is a
      member of the degenerin gene family (genes such as mec-4 and deg-1 that can be
      mutated to cause neurodegeneration). Because components of an amiloride-sensitive
      sodium channel (alpha, beta and gamma rENaC) from rat share considerable sequence
      similarity with the C. elegans genes, it is likely that degenerins may function
      as channel proteins. Here we show that two degenerin homologues (mec-4 and mec
      10) are expressed in the same cells, although each provides a unique function.
      Based on genetic data of mutations affecting mec-10-induced degeneration, we
      propose that the products of three genes (mec-4, mec-10 and mec-6) form a complex
      needed for mechanosensation, and that several other mec genes may be important in
      regulating the putative channel complex.

PMID- 7509040
TI  - Insight into E-selectin/ligand interaction from the crystal structure and
      mutagenesis of the lec/EGF domains.
AB  - The three-dimensional structure of the ligand-binding region of human E-selectin
      has been determined at 2.0 A resolution. The structure reveals limited contact
      between the two domains and a coordination of Ca2+ not predicted from other C
      type lectins. Structure/function analysis indicates a defined region and specific
      amino-acid side chains that may be involved in ligand binding. These features of
      the E-selectin/ligand interaction have important implications for understanding
      the recruitment of leukocytes to sites of inflammation.

PMID- 7509041
TI  - S proteins control rejection of incompatible pollen in Petunia inflata.
AB  - Flowering plants have evolved various stratagems to prevent inbreeding and
      promote outcrosses. One such mechanism, gametophytic self-incompatibility,
      provides a genetic barrier to self-fertilization, and in the simplest cases is
      controlled by the highly polymorphic S locus. Growth of a pollen tube in the
      style is arrested when the S allele carried by the pollen matches one of the two
      S alleles carried by the pistil. Putative S allele proteins of the pistil have
      been identified in several solanaceous species based on their co-segregation with
      S alleles, and they have been shown to be ribonucleases. So far, there has been
      only correlative or indirect evidence for the claim that these S allele
      associated proteins (S proteins) are involved in recognition and rejection of
      self pollen. Here we show that inhibition of synthesis of S3 and S2 proteins in
      Petunia inflata plants of S2S3 genotype by the antisense S3 gene resulted in
      failure of the transgenic plants to reject S3 and S2 pollen. We further show that
      expression of the transgene encoding S3 protein in P. inflata plants of S1S2
      genotype confers on the transgenic plants the ability to reject S3 pollen. The
      self-incompatibility behaviour of the pollen was not affected by the transgene in
      either set of experiments. Taken together, these findings provide direct in vivo
      evidence that S proteins control the self-incompatibility behaviour of the
      pistil.

PMID- 7509042
TI  - Initial events of myelination involve Fyn tyrosine kinase signalling.
AB  - Myelin is the lipoprotein multimembrane that functions as an insulator preventing
      the flow of ion currents across the axonal membrane and facilitating the
      conduction of nerve impulses. It is synthesized by oligodendrocytes in the
      central nervous system at about the time of birth in mammals. During the initial
      stages of myelination, several proteins are phosphorylated on tyrosine. Among
      these proteins, we identified Fyn tyrosine kinase, one of the non-receptor-type
      tyrosine kinases of the Src family. Here we report that Fyn tyrosine kinase is
      activated during the initial stages of myelination and that it is associated with
      the large myelin-associated glycoprotein (MAG), an adhesion molecule that has
      been implicated in myelinogenesis. The Fyn-large MAG association requires amino
      terminal domains of Fyn that include SH2 and SH3 (Src homology domains 2 and 3).
      Crosslinking of large MAG with antibody induces a rapid increase in the specific
      activity of Fyn kinase. These results indicate that Fyn participates in the
      initial events of myelination as a signalling molecule downstream of large MAG;
      indeed, we find that fyn-deficient mice exhibit impaired myelination.

PMID- 7509043
TI  - Molecular and cellular mechanisms of general anaesthesia.
AB  - General anaesthetics are much more selective than is usually appreciated and may
      act by binding to only a small number of targets in the central nervous system.
      At surgical concentrations their principal effects are on ligand-gated (rather
      than voltage-gated) ion channels, with potentiation of postsynaptic inhibitory
      channel activity best fitting the pharmacological profile observed in general
      anaesthesia. Although the role of second messengers remains uncertain, it is now
      clear that anaesthetics act directly on proteins rather than on lipids.

PMID- 7509044
TI  - A cell initiating human acute myeloid leukaemia after transplantation into SCID
      mice.
AB  - Most human acute myeloid leukaemia (AML) cells have limited proliferative
      capacity, suggesting that the leukaemic clone may be maintained by a rare
      population of stem cells. This putative leukaemic stem cell has not been
      characterized because the available in vitro assays can only detect progenitors
      with limited proliferative and replating potential. We have now identified an AML
      initiating cell by transplantation into severe combined immune-deficient (SCID)
      mice. These cells homed to the bone marrow and proliferated extensively in
      response to in vivo cytokine treatment, resulting in a pattern of dissemination
      and leukaemic cell morphology similar to that seen in the original patients.
      Limiting dilution analysis showed that the frequency of these leukaemia
      initiating cells in the peripheral blood of AML patients was one engraftment unit
      in 250,000 cells. We fractionated AML cells on the basis of cell-surface-marker
      expression and found that the leukaemia-initiating cells that could engraft SCID
      mice to produce large numbers of colony-forming progenitors were CD34+ CD38-;
      however, the CD34+ CD38+ and CD34- fractions contained no cells with these
      properties. This in vivo model replicates many aspects of human AML and defines a
      new leukaemia-initiating cell which is less mature than colony-forming cells.

PMID- 7509045
TI  - Howard M. Temin (1934-94)

PMID- 7509046
TI  - Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic
      linker of the alpha 1-subunit.
AB  - The beta-subunit is an integral component of purified voltage-sensitive Ca2+
      channels. Modulation of Ca2+ channel activity by the beta-subunit, which includes
      significant increases in transmembrane current and/or changes in kinetics, is
      observed on coexpression of six alpha 1-subunit genes with four beta-subunit
      genes in all alpha 1-beta combinations tested. Recent reports suggest that this
      regulation is not due to targeting of the alpha 1-subunit to the plasma membrane
      but is probably a result of a conformational change induced by the beta-subunit.
      Here we report that the beta-subunit binds to the cytoplasmic linker between
      repeats I and II of the dihydropyridine-sensitive alpha 1-subunits from skeletal
      (alpha 1S) and cardiac muscles (alpha 1C-a), and also with the more distantly
      related neuronal alpha 1A and omega-conotoxin GVIA-sensitive alpha 1B-subunits.
      Sequence analysis of the beta-subunit binding site identifies a conserved motif
      (QQ-E--L-GY--WI--E) positioned 24 amino acids from the IS6 transmembrane domain
      in each alpha 1-subunit. Mutations within this motif reduce the stimulation of
      peak currents by the beta-subunit and alter inactivation kinetics and voltage
      dependence of activation. Conservation of the beta-subunit binding motif in these
      functionally distinct calcium channels suggests a critical role for the I-II
      cytoplasmic linker of the alpha 1-subunit in channel modulation by the beta
      subunit.

PMID- 7509048
TI  - Glutamate- and AMPA-mediated calcium influx through glutamate receptor channels
      in medial septal neurons.
AB  - The Ca(2+)-fraction of the ion current flowing through glutamate receptor
      channels activated either by glutamate or by AMPA was determined in forebrain
      neurons of the rat medial septum. By combining whole-cell patch-clamp and fura-2
      fluorometric measurements we found that, at negative membrane potentials and at
      an extracellular free Ca(2+)-concentration of 1.6 mM, the Ca(2+)-fraction of the
      current activated by glutamate is 5.7%. A pharmacological analysis of responses
      produced by ionophoretically-released glutamate demonstrated a large contribution
      of NMDA-receptors but a small contribution of AMPA/kainate receptors to these
      responses. Interestingly, also AMPA-mediated currents were associated with
      significant changes in Ca(2+)-sensitive fluorescence. The fractional Ca2+ current
      of AMPA-induced responses was 1.2 +/- 0.4% (n = 5).

PMID- 7509047
TI  - Immunohistochemical studies of extracellular matrix components and integrins in
      IgA nephropathy.
AB  - Localization of adhesive glycoproteins as the extracellular matrix and their cell
      surface receptors (integrins) were studied in an attempt to clarify their roles
      in the progression and aggravation of IgA nephropathy. The relationship between
      their localization and factors associated with clinical progression was then
      investigated in 65 patients with IgA nephropathy. The indirect immunoperoxidase
      method was used to study the distribution of fibronectin (FN), vitronectin (VN),
      fibronectin receptor (FNR) and vitronectin receptor (VNR). In all cases, FN was
      present in the glomeruli, mainly confined to the mesangial region, and in some
      cases, it was observed along the glomerular capillary loops. An expanded
      mesangial region accompanied higher FN distribution. FNR was present in the
      mesangial region and glomerular capillary loops, and was higher in the expanded
      mesangial region. VN was positive in 51 of 65 cases. In all cases, VNR was
      present in the mesangium and glomerular capillary loops, and its distribution was
      more predominant in and along the capillary loops than in the mesangial region.
      The expanded mesangium accompanied higher VNR distribution. There was a
      significant correlation in distribution between all factors with the exception of
      VN and FNR. FN, FNR and VNR increased significantly as a degree of histological
      damage. However, VN was not significantly associated with the degree of
      histological damage in positive and negative groups. The distribution of FN, FNR
      and VNR was associated with clinical aggravation factors although the
      distribution of VN was not. In conclusion, the distribution and functional
      alteration of FN and integrins in the glomeruli appear to be involved in the
      progression and exacerbation of IgA nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509049
TI  - The developmental onset of NMDA receptor-channel activity during neuronal
      migration.
AB  - Patch-clamp recordings of granule cells in thin slices of developing rat
      cerebellum maintained in vitro displayed spontaneous single-channel activity
      mediated via activation of N-methyl-D-aspartate (NMDA) receptors. The frequency
      of tonic single-channel activity was reversibly inhibited by the NMDA
      receptor/channel antagonists D-2-amino-5-phosphonovalerate (D-AP5), 7-chloro
      kynurenate (7-Cl-Kynu) and MgCl2, potentiated by glycine, and unaffected by 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX) or tetrodotoxin (TTX). Tonic channel
      activity was also reversibly inhibited by enzymatic degradation of endogenous
      glutamate by glutamate pyruvate transaminase, which did not affect the NMDA
      sensitivity of granule cells. Both the frequency of spontaneous channel activity
      and the NMDA sensitivity were low in premigratory cells of the external germinal
      layer (EGL), with large increases observed in migrating cells in the molecular
      layer (ML) and in postmigratory cells within the internal granule cell layer
      (GCL). Tonic channel activity was enhanced by the glutamate uptake inhibitor L
      alpha-aminoadipate (L-alpha-AA), the degree of enhancement being greater in the
      EGL than the GCL. The results demonstrate that a dramatic increase in the tonic
      NMDA receptor-channel activity occurs during the stages of granule cell
      differentiation, migration and synaptogenesis, which is driven by endogenous
      glutamate release and regulated by NMDA receptor density and local glutamate
      uptake.

PMID- 7509050
TI  - Nitric oxide, superoxide and peroxynitrite: putative mediators of NMDA-induced
      cell death in cerebellar granule cells.
AB  - In this study, we analysed the implication of superoxide (O2-.) and nitric oxide
      (NO.) free radicals and their resulting product peroxynitrite (ONOO-) in the
      neuronal death induced by the activation of the glutamatergic receptor of the N
      methyl-D-aspartate (NMDA) subtype using cultured cerebellar granule cells. The
      NOl donor SIN-1 (3-morpholinosydnonimine N-ethylcarbamide), at concentrations
      which produced a much higher guanylate cyclase activation (i.e. NO.
      concentration) than NMDA, was not neurotoxic and did not increase the NMDA
      induced neuronal death. The absence of involvement of NO. in NMDA-induced
      neuronal death was confirmed by the ineffectiveness of L-NG-nitroarginine (L
      Narg) as a neuroprotective compound. Electron paramagnetic resonance (EPR)
      experiments, using 5,5-dimethyl pyrroline 1-oxide (DMPO) as a spin trap,
      indicated that NMDA receptor stimulation led to the generation of O2-. from at
      least 15-30 min. The generation of O2-. by xanthine (XA)-xanthine oxidase (XO)
      induced a neuronal death similar to that of NMDA. XA-XO-induced neuronal death
      was suppressed by addition of either superoxide dismutase (SOD) plus catalase
      (CAT), or DMPO in the incubation medium. In contrast, NMDA-induced neuronal death
      was widely blocked by DMPO and other spin trap compounds, but not by SOD +/- CAT.
      XA-XO-induced neuronal death was not potentiated by SIN-1 indicating that ONOO-
      is not more toxic than O2-. in our neuronal model.

PMID- 7509051
TI  - The nitric oxide-cyclic GMP signalling pathway in rat brain.
AB  - Nitric oxide is a novel signalling molecule in the brain and a potent activator
      of the cyclic GMP-synthesising enzyme, soluble guanylate cyclase. To determine if
      stimulation of cyclic GMP formation is a widespread mechanism of nitric oxide
      signal transduction, we have compared the distribution of the nitric oxide
      generating enzyme (nitric oxide synthase) with that of nitric oxide-stimulated
      cyclic GMP accumulation, throughout the rat brain. The former was done using
      NADPH diaphorase histochemistry and the latter by cyclic GMP immunohistochemistry
      following perfusion of the nitric oxide donor, nitroprusside, in vivo. At a gross
      level, there was generally a good match when the two were compared in adjacent
      sections. Although the relative staining intensity varied from area to area, in
      no grey matter region did we observe cyclic GMP accumulation in the absence of
      nitric oxide synthase staining. In detail, the locations were complementary
      rather than identical. In some areas, nitric oxide synthase was found in
      postsynaptic structures and cyclic GMP accumulation in presynaptic elements and
      fibres; in others, the locations were reversed. Glial cells and their processes
      also accumulated cyclic GMP in the cerebellum. The results suggest that soluble
      guanylate cyclase is a major nitric oxide "receptor" throughout the brain. They
      also support the hypothesis that nitric oxide generated therein primarily
      functions as a mediator of cell-cell signaling rather than as a conventional
      second messenger acting within the cells in which it is produced. The types of
      communication subserved by nitric oxide appear to be extraordinarily diverse.

PMID- 7509052
TI  - Nordihydroguaiaretic acid attenuates NMDA neurotoxicity--action beyond the
      receptor.
AB  - There is widespread interest in the neurotoxicity of the endogenous excitatory
      amino acid neurotransmitter glutamate. Excessive glutamate release or
      accumulation leads to neuronal injury or death in a variety of experimental
      models of ischemia, anoxia and hypoglycemia. This injury appears to be caused by
      overactivation of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors
      since a variety of competitive and uncompetitive NMDA antagonists can attenuate
      this process, sometimes in a dramatic fashion. Given the clinical context in
      which this form of neuronal injury occurs, it would be desirable if we could
      identify agents that blocked NMDA toxicity, after initial receptor binding and
      ion channel fluxes had transpired. Because NMDA receptor activation initiates the
      arachidonic acid cascade, we have recently looked at whether the phospholipase A2
      and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) can reduce NMDA
      neurotoxicity in vitro. In the concentration range 1-30 microM, NDGA diminished
      the death of cultured rodent hippocampal neurons produced by 100 microM NMDA.
      When 30 microM NDGA was present both before and after NMDA exposure, death
      declined by over 50%. NDGA did not block NMDA-induced inward currents in voltage
      clamped neurons, so the drug is not a direct NMDA receptor antagonist. It also
      had no effect on the elevation in intracellular calcium produced by NMDA
      exposure. It is likely that NDGA acts at a site(s) distal to the NMDA receptor
      and the neuronal membrane to limit NMDA toxicity. We are hopeful that strategies
      for limiting excitotoxicity, which halt destructive intracellular events, can be
      developed for use in human neurological diseases linked to excessive stimulation
      of glutamate receptors.

PMID- 7509053
TI  - Characterization and expression of the Xenopus c-Myb homolog.
AB  - The c-Myb protein is a sequence specific DNA-binding transcriptional regulator
      that is critically involved in the regulation of hematopoietic differentiation.
      Its role in these processes suggests that the function of c-Myb may be important
      early in the establishment of the hematopoietic lineage. We have isolated cDNA
      and partial genomic clones representing the Xenopus c-Myb homolog (Xc-Myb) in
      order to examine the role this gene plays in early mesodermal patterning in the
      frog embryo. The establishment of these clones as c-Myb homologs, as opposed to
      Myb-related sequences, is based upon both predicted amino acid sequences and the
      location of the exon-intron boundaries within the Xc-Myb gene. Maternally derived
      Xc-Myb RNA is degraded following fertilization then, beginning at midblastula, re
      accumulates throughout early development. Xc-Myb RNA is localized to the animal
      cap region of the early blastula. Following the onset of gastrulation expression
      predominates in the ventral half of the embryo. During neurulation expression of
      Xc-Myb is observed in both the anterior dorsal and ventral vegetal regions of the
      embryo. Expression of Xc-Myb occurs in several adult tissues, the highest levels
      of which are in the intestine, heart, liver, lung and ovary. Xc-Myb encodes a
      protein of 624 amino acids and exhibits a mobility in SDS-PAGE of approximately
      75 kDa, identical with that of the murine c-Myb protein. Xc-Myb protein exhibits
      70% identity with avian and 67% identity with mammalian c-Myb proteins.

PMID- 7509054
TI  - Chronic respiratory failure of infancy and childhood: clinical outcomes based on
      underlying etiology.
AB  - To assess whether underlying diagnosis affects morbidity and mortality outcomes
      in patients with chronic respiratory failure, we studied 55 patients with chronic
      respiratory failure of infancy and childhood (CRFIC). Entry criteria included
      patients with chronic respiratory failure due to static neurologic or
      neuromuscular conditions or secondary to other disease processes considered
      likely to improve or resolve over time. Subjects were grouped into those having
      chronic lung disease (CLD, n = 22), neurologic or neuromuscular diseases (NM, n =
      21), or congenital abnormalities affecting the respiratory system (CA, n = 12).
      The average duration of follow-up was 21.3 months. There were no differences
      between groups in mortality with only four deaths (7%). Patients with CLD fared
      better than those with NM or CA in duration of ventilatory support, duration of
      tracheostomy, percentage of successful weaning from mechanical ventilation, and
      neurodevelopmental outcomes. Subjects with CLD had a significantly greater
      frequency of tracheomalacia (86%), feeding disorders (86%), and
      hypogammaglobulinemia G (77%). There were no differences between groups for
      respiratory readmissions or family dysfunction. We conclude that almost all
      patients with CRFIC will survive, but morbidity outcomes will vary based on the
      underlying diagnosis.

PMID- 7509055
TI  - [Radiologic-pathologic correlation of experimental bleomycin-induced
      pneumonitis].
AB  - Radiologic-pathologic correlative study of bleomycin-induced pneumonitis was
      performed using inflated and fixed lung specimens. Sixteen male Japanese white
      rabbits (body weight: 2.0-2.5 kg) were given a single intratracheal injection of
      10 mg/kg bleomycin. On day 3, 10, 21, and 42 after bleomycin administration, 4
      rabbits were killed, and each lung was inflated and fixed for radiologic
      pathologic correlation. Early pathologic change involved a markedly exudative
      lesion like DAD, corresponding to the finding of markedly increased density on
      soft X-ray. As intraalveolar organization progressed, fibrotic changes of the
      alveolar septum, and atelectatic change evolved pathologically, the finding of
      markedly increased density developed the nature of contraction, and finally the
      finding of an abnormal linear shadow and air space dilatation were formed. The
      finding of markedly increased density and slightly increased density,
      respectively, did not simply correspond to the alveolar lesion and interstitial
      lesion pathologically. We considered that the degree of increased density
      depended on the degree of air content in the alveoli of the lesion. The finding
      of an abnormal linear shadow corresponded to the band of fibrotic tissue, and
      band-shaped atelectasis of alveoli. The finding of air space dilatation
      corresponded to the dilatation of respiratory bronchioli and alveolar ducts in
      the fibrotic stage, and this may show the mechanism of honeycomb lung formation.
      The finding of a clearly demarcated shadow with linear margins could be
      recognized as a lobular lesion and disappeared as fibrotic change evolved.

PMID- 7509057
TI  - Cumulative 16-year index. Volumes 1-16, 1978-1993.

PMID- 7509056
TI  - Lipotrope-modified diets enhance nitrosomethylurea-induced mammary carcinogenesis
      in female rats.
AB  - This study was conducted to determine the effects of lipotrope-modified
      (deficient or supplemented) diets on nitrosomethylurea- (NMU) induced mammary
      tumorigenesis. Eighty female Sprague-Dawley rats (4 wks old) were assigned to one
      of the following groups: control-synthetic diet (CSD), containing all required
      lipotropes; choline-methionine-deficient diet (CMD); methyl-deficient diet (MDD),
      lacking all lipotropes; and methyl-supplemented diet (MSD), containing twice as
      much of each lipotrope as the CSD diet. All animals were injected with NMU after
      a three-week dietary treatment period. MDD and MSD groups had shorter tumor
      latency periods (73 and 74 days, respectively) than the CSD group (105 days).
      Number of tumors per rat was significantly increased in the MDD group (4.6)
      compared with CSD (1.6), CMD (2.1), and MSD (2.5) groups. The results indicate
      that dietary manipulation of lipotropes in young female rats enhanced NMU-induced
      mammary tumorigenesis.

PMID- 7509059
TI  - Review of human dendritic cells: isolation and culture from precursors.
AB  - There is no single characteristic or marker that identifies a dendritic cell.
      This review of the methods used for dendritic cell identification stresses that
      changes occur over the lifetime and changing functional status of the cell. Human
      dendritic cell populations have been obtained from adult peripheral blood,
      umbilical cord blood, bone marrow, thymus, and monocytes as starting substrates.
      Most recently dendritic cell populations have been grown from separated
      hematopoietic precursors, suggesting that there is a common granulocyte-monocyte
      dendritic cell progenitor. Whether monocytes and dendritic cells can be modulated
      back and forth remains an open question. Granulocyte-monocyte colony stimulating
      factor (GM-CSF) appears to be critical to the development and function of these
      enriched and cultured cells. The characteristics of the cells produced by these
      various methods are tabulated. Important to the understanding of Langerhans cell
      biology is the variation in CD1 expression under different circumstances.

PMID- 7509058
TI  - Fetal megakaryocytic dyshemopoiesis in Down syndrome: association with hepatic
      and pancreatic fibrosis.
AB  - Trisomy 21 was diagnosed by prenatal blood sampling at 30 and 31 weeks of
      gestation, respectively, in two fetuses with hepatosplenomegaly. In both, the
      fetal blood contained blast cells and cells showing megakaryocytic
      differentiation. Case 1 died neonatally 1 week later and the cellular
      infiltration causing enlargement of liver and spleen had a
      megakaryocytic/megakaryoblastic component staining positively for von Willebrand
      factor and binding to Ulex europaeus 1. Case 2, when stillborn 4 weeks later, had
      remarkably severe hepatic and pancreatic fibrosis. Cells in pulmonary vessels had
      morphology and immunohistochemical reactions consistent with
      megakaryocytic/megakaryoblastic differentiation. Comparison of the two cases
      suggests that the visceral fibrosis of perinatal Down syndrome may progress very
      rapidly in utero. They demonstrate further the association of the fibrosis with a
      dyshemopoiesis in which there is proliferation of cells of megakaryocytic lineage
      and a close relationship to the transient leukemia of neonatal Down syndrome.

PMID- 7509060
TI  - Characterization of a persistent inhibitory action of L-364,718 on
      cholecystokinin-stimulated enzyme secretion in pancreatic acini.
AB  - Examining the actions of L-364,718 on rat pancreatic acini, we found that L
      364,718 causes persistent inhibition of cholecystokinin (CCK)-8-stimulated enzyme
      secretion in acini that were first incubated with L-364,718, washed repeatedly,
      and then reincubated with CCK-8. This inhibition is maximal after as little as 5
      s of first incubation with L-364,718, is unaltered by reducing the temperature of
      the first incubation from 37 to 4 degrees C and is specific for CCK-8 in that
      carbachol-stimulated enzyme secretion is unaltered. The inhibitory potency of L
      364,718 added to the first incubation followed by washing and reincubation with
      CCK-8 is nearly the same as when L-364,718 is added together with CCK-8 in the
      same incubation. The persistent inhibitory action of L-364,718 is not
      attributable to residual free L-364,718 in the bulk phase of the second
      incubation medium. In addition, L-364,718 does not cause persistent inhibition by
      binding irreversibly to CCK receptors because the binding reaction is completely
      reversible and the persistent inhibition can be surmounted with appropriate
      concentrations of CCK-8. When acini are first incubated with L-364,718 and washed
      repeatedly, approximately 0.2% of the original L-364,718 remains trapped in a
      microenvironment within the acini. This trapping presumably results in a
      sufficiently high concentration of L-364,718 to produce its persistent, albeit
      surmountable inhibition.

PMID- 7509062
TI  - Comparison between the effects of VIP and the novel peptide PACAP on the exocrine
      pancreatic secretion of the rat.
AB  - The effect of intravenous infusion of pituitary adenylate cyclase-activating
      peptide (PACAP) 27, a novel regulatory peptide that shows a close structural and
      chemical similarity to vasoactive intestinal peptide (VIP), on the rat exocrine
      pancreatic secretion was studied. PACAP and VIP stimulated the flow rate of
      exocrine pancreatic secretion (p < 0.05). However, protein output and amylase
      secretion were mainly stimulated by PACAP. Intravenous infusion of VIP increased
      the plasma levels of secretin (p < 0.05). On the other hand, PACAP released
      neither secretin nor VIP. Our results show: (a) both PACAP and VIP stimulate
      exocrine pancreatic secretion, (b) PACAP stimulation of pancreatic amylase and
      protein secretion is greater than that induced by VIP, and (c) PACAP probably
      exerts a direct effect on exocrine pancreas whereas some of the actions of VIP
      might be mediated by secretin.

PMID- 7509061
TI  - Effect of intraduodenal bile and taurodeoxycholate on exocrine pancreatic
      secretion and on plasma levels of vasoactive intestinal polypeptide and
      somatostatin in man.
AB  - Intraduodenal (i.d.) application of bile or Na-taurodeoxycholate (TDC) dose
      dependently enhances basal exocrine pancreatic secretion. The hydrokinetic effect
      is mediated at least in part by secretin. This study should show, whether
      vasoactive intestinal polypeptide (VIP), a partial agonist of secretin, may also
      be involved in the mediation of the hydrokinetic effect. Furthermore, plasma
      concentrations of somatostatin-like immunoreactivity (SLI) were measured in order
      to check whether this counterregulating hormone is also released by bile and TDC.
      Twenty investigations were carried out on 10 fasting healthy volunteers provided
      with a double-lumen Dreiling tube. Bile and TDC were intraduodenally applied in
      doses of 2-6 g and 200-600 mg, respectively, at 65-min intervals. Plasma samples
      were withdrawn at defined intervals for radioimmunological determination of VIP
      and SLI. Duodenal juice was collected in 10-min fractions and analyzed for
      volume, pH, bicarbonate, lipase, trypsin, and amylase. I.d. application of bile
      or TDC dose dependently stimulated hydrokinetic and ecbolic pancreatic secretion.
      Bile exerted a slightly stronger effect than TDC. Pancreatic response was
      simultaneously accompanied by a significant increase of plasma VIP and SLI
      concentrations. The effect of bile on integrated plasma VIP and SLI
      concentrations seems to be dose dependent; the effect of TDC on integrated SLI,
      too. For the increase of integrated plasma VIP concentrations after TDC no dose
      response relation could be established. We conclude that VIP may be a further
      mediator of bile-induced volume and bicarbonate secretion.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7509063
TI  - Isolation and culture of rhesus monkey pancreatic ductules and ductule-like
      epithelium.
AB  - The objective of this work was to devise methods for the isolation and culture of
      duct epithelium from rhesus monkey pancreas with the expectation that such
      methods would be applicable to the human pancreas. This objective is important
      because of the role duct epithelium appears to play in human diseases such as
      pancreatic cancer and cystic fibrosis. Pieces of freshly procured pancreas were
      minced and enzymatically dissociated, resulting in a digest that contained a few
      isolated ductules (intralobular ducts) as well as numerous small tissue fragments
      consisting of roughly equal proportions of ductular and acinar cells. These
      fragments were suspended in a rat tail collagen gel and cultured for up to 2
      weeks in a medium supplemented with cholera toxin, epidermal growth factor, and
      other additives. A few cystic ductular fragments were initially observed among a
      large number of predominantly solid fragments. Later, most of the solid fragments
      also became cystic and eventually resembled the ductules except for being
      spherical. Autoradiographic analysis of DNA synthesis showed that the cysts
      possessed a proliferative potential. The cysts consisted almost entirely of
      ductule-like epithelium with no recognizable acinar cells, and exhibited greatly
      reduced concentrations of the acinar marker enzymes amylase, chymotrypsin, and
      gamma-glutamyl transferase. In contrast, the specific activity of the duct marker
      enzyme carbonic anhydrase was elevated in freshly isolated digests compared with
      the whole pancreas and this elevated activity was maintained for 4-5 days of
      culture, after which it declined. Other evidence for the ductular nature of the
      cysts was their low density relative to freshly isolated acinar tissue, their
      ability to distend (suggestive of fluid/electrolyte secretion), and the
      accumulation of mucins at the apical borders of the cells. The results show that
      fragments of rhesus monkey pancreas that are enriched in ductular epithelium
      assume some of the properties of ductular cells when cultured in a collagen gel.
      These epithelial preparations should facilitate biochemical and physiological
      studies of this important pancreatic cell type.

PMID- 7509064
TI  - Separation of canine pancreatic juice proteins by hydrophobic interaction
      chromatography preserves enzyme activity.
AB  - To measure the synthesis of pancreatic enzymes requires the separation of
      pancreatic juice proteins. The aim of the present study was to separate amylase,
      lipase, and trypsinogen present in dog pancreatic juice by using a hydrophobic
      interaction high-performance liquid chromatography (HPLC). During a 40-min, four
      stage gradient of decreasing sodium sulfate concentration, dog pancreatic juice
      proteins were separated into 10 peaks based on hydrophobicity. Amylase, lipase,
      and trypsinogen were identified in HPLC fractions by measuring enzyme activity
      and molecular weight. Amylase and lipase were present in separate peaks. By
      sodium dodecyl sulfate (SDS) gel electrophoresis, peak 10, the only peak with
      amylase activity had a single protein, but peak 3, containing lipase, and peak 9,
      containing trypsinogen, had two or more proteins. Trypsinogen activity was also
      detected as a main protein in peak 5 and the molecular weight of this protein, 26
      kDa corresponds to that of dog trypsinogen. Trypsinogen was not identified in
      peak 9 by SDS gel electrophoresis because other proteins were close to this
      location on the gel. In summary, the proteins and activities of amylase, lipase,
      and two trypsinogens secreted by the dog pancreas can be separated rapidly by
      hydrophobic interaction liquid chromatography. Also, this one step procedure
      recovers 87% of amylase from dog pancreatic juice as a single protein.

PMID- 7509065
TI  - Role of oxygen-derived free radicals in hemorrhagic pancreatitis induced by
      stress and cerulein in rats.
AB  - The role of oxygen-derived free radicals in the pathogenesis of acute
      pancreatitis was studied in a new model of acute hemorrhagic pancreatitis and
      cerulein-induced edematous pancreatitis in rats. Hemorrhagic pancreatitis was
      produced by administering two intraperitoneal doses of cerulein [40 micrograms/kg
      body weight (BW)] at 1-h intervals following water immersion stress applied for 5
      h. Edematous pancreatitis was induced by injecting cerulein as described but
      without water immersion. Five hours after the first injection of cerulein,
      pancreatic edema and elevation of serum amylase level were more marked in the
      animals with hemorrhagic than with edematous pancreatitis. Five hours after the
      first injection of cerulein, marked hemorrhage and venous dilatation were
      observed only in those with hemorrhagic pancreatitis. Local pancreatic blood flow
      decreased to approximately 60% of control values in the animals with edematous
      pancreatitis, and to approximately 30% of control values in those with
      hemorrhagic pancreatitis. To evaluate the involvement of oxygen radicals, some
      rats received three intraperitoneal injections of superoxide dismutase (SOD
      10,700 U/kg BW) and catalase (132,000 U/kg BW) beginning 15 min before the first
      injection of cerulein and repeated at 1-h intervals. No significant effect of
      free radical scavengers was observed on the edematous pancreatitis. However, in
      hemorrhagic pancreatitis, treatment with SOD and catalase completely suppressed
      the hemorrhage and venous dilatation of the pancreas, significantly reduced the
      pancreatic wet weight and the serum amylase level, and reduced the histologic
      alterations. However, after treatment with SOD and catalase, no differences were
      observed in local pancreatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509066
TI  - Prostaglandin D2, F2 alpha, E2, and E1 in early phase of experimental acute
      necrohemorrhagic pancreatitis in rats.
AB  - Changes in endogenous pancreas production of prostaglandins D2, F2 alpha, E2, and
      E1 in early stages of acute necrotizing pancreatitis induced by intraductal
      administration of 3.5% sodium taurocholate have been determined by
      radioimmunoassay of chromatographically purified tissue extracts. For this
      purpose 18 male Wistar rats were randomized in three groups: control,
      pancreatitis, and pancreatitis plus indomethacin. Pancreas tissue samples were
      obtained 5 min after pancreatitis induction. In the pancreatitis-induced group,
      prostaglandins D2, F2 alpha, and E2 show significantly increased tissue levels
      relative to the controls whereas prostaglandin E1 remains unmodified. These
      results suggest a role for series 2 prostaglandins in the earlier stages of
      pancreatitis.

PMID- 7509067
TI  - Effects of secretin and caerulein on pancreatic digestive enzymes in cultured rat
      acinar cells.
AB  - Caerulein is proposed to regulate the synthesis of pancreatic proteases and
      amylase. Similarly, secretin is implicated in the regulation of pancreatic lipase
      synthesis. Evidence of these regulations is predominantly from in vivo studies.
      We therefore examined the effects of caerulein and secretin directly on acinar
      cells to eliminate possible interactions with other regulatory factors. Cellular
      and media enzyme activities and relative synthesis were measured after 24 h of
      hormonal treatment. Cells were incubated with [14C]-amino acids and then
      subjected to two-dimensional gel electrophoresis to separate individual acinar
      proteins for subsequent determination of incorporated radioactivity and relative
      synthesis. In general, all enzyme activities decreased (33%; p < 0.02) over time
      in culture and medium enzyme activities increased (370%; p < 0.00001) in all
      treatment groups. Caerulein further decreased cellular content of all enzymes (p
      < 0.002) and increased media amylase and lipase activities (p < 0.02). Caerulein,
      however, significantly increased the relative synthesis of trypsin (28%) and
      tended to increase that of chymotrypsin (25%; p < 0.06), which supports its
      proposed role in protease regulation. Secretin, on the other hand, did not
      significantly affect the cellular or medium activities or the relative synthesis
      of any pancreatic enzyme evaluated. Therefore, this study does not support the
      proposed role of secretin in lipase regulation.

PMID- 7509068
TI  - Vaccination of chimpanzees against infection by the hepatitis C virus.
AB  - A high incidence of community-acquired hepatitis C virus infection that can lead
      to the progressive development of chronic active hepatitis, liver cirrhosis, and
      primary hepatocellular carcinoma occurs throughout the world. A vaccine to
      control the spread of this agent that represents a major cause of chronic liver
      disease is therefore needed. Seven chimpanzees (Pan troglodytes) have been
      immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)]
      that were copurified from HeLa cells infected with a recombinant vaccinia virus
      expression vector. Despite the induction of a weak humoral immune response to
      these viral glycoproteins in experimentally infected chimpanzees, a strong
      humoral immune response was obtained in all vaccines. The five highest responders
      showed complete protection against an i.v. challenge with homologous hepatitis C
      virus 1. The remaining two vaccines became infected, but both infection and
      disease may have been ameliorated in comparison with four similarly challenged
      control chimpanzees, all of which developed acute hepatitis and chronic
      infections. These results provide considerable encouragement for the eventual
      control of hepatitis C virus infection by vaccination.

PMID- 7509069
TI  - Structure, function, and phylogeny of [Arg8]vasotocin receptors from teleost fish
      and toad.
AB  - [Arg8]Vasotocin (AVT) is considered to be the most primitive known vertebrate
      neurohypophyseal peptide of the vasopressin/oxytocin hormone family and may thus
      be ancestral to all the other vertebrate peptide hormones. The molecular
      evolution of the corresponding receptor family has now been studied by cloning an
      AVT receptor, consisting of 435 amino acid residues, from the teleost fish, the
      white sucker Catostomus commersoni. Frog oocytes injected with the AVT receptor
      encoding cRNA respond to the application of AVT, but not to its structural and
      functional counterpart isotocin, by an induction of membrane chloride currents
      indicating the coupling of the AVT receptor to the inositol phosphate/calcium
      pathway. The pharmacological properties of the expressed AVT receptor show that
      it represents, or is closely related to, an ancestral nonapeptide receptor:
      oxytocin, aspargtocin, mesotocin, and vasopressin activated the receptor, but
      other members of the vasopressin/oxytocin family tested showed little or no
      potency; antagonists of the mammalian vasopressin V1 and oxytocin receptors
      blocked the AVT response. Comparison of AVT receptor sequences spanning
      transmembrane domains two to five, deduced by cloning cDNAs from the Pacific
      salmon Oncorhynchus kisutch, the cave-dwelling fish Astyanax fasciatus, and the
      anuran Xenopus laevis, with those of their mammalian counterparts emphasizes
      amino acid residues that are involved in hormone binding. The presence of a 5.0
      kb transcript in various teleost tissues (pituitary, liver, gills, swim bladder,
      and lateral line) points to a physiological role for the fish AVT receptor in
      metabolic, osmoregulatory, and sensory processes.

PMID- 7509070
TI  - Growth hormone (GH) induces tyrosine-phosphorylated proteins in mouse L cells
      that express recombinant GH receptors.
AB  - Porcine and bovine GH receptor (GHR) cDNAs were stably expressed in mouse L
      cells, which normally do not possess detectable levels of mouse GHR. Expression
      of the GHR cDNAs resulted in specific binding of 125I-labeled GH by these cell
      lines. To study GHR-related signaling events in these cells, protein tyrosine
      phosphorylation was examined. In GH-treated cells, a tyrosine-phosphorylated
      protein with a molecular mass of approximately 95 kDa (pp95) was increased
      dramatically (approximately 100-fold) relative to non-GH-treated cells. The
      amount of pp95 within the cells after GH treatment was positively correlated with
      the number of GHRs on the cells. Tyrosine phosphorylation of pp95 could not be
      induced by prolactin, insulin, insulin-like growth factor I, interleukin 2,
      epidermal growth factor, platelet-derived growth factor, or fibroblast growth
      factor. Phosphorylation of pp95 was found to be a rapid event that could be
      observed 60 sec after GH treatment. Also, pp95 appears to exist as a complex of
      two proteins, i.e., pp95 and pp96. The GH-induced response by these cells may be
      of use in screening GH analogs for biological activity.

PMID- 7509071
TI  - Evidence supporting a tethered tracking model for helicase activity of
      Escherichia coli Rho factor.
AB  - Transcription termination factor Rho of Escherichia coli has an ATP-dependent
      RNA.DNA helicase activity that presumably facilitates RNA transcript release from
      the elongation complex. This helicase activity is unidirectional (5' to 3') and
      is stoichiometric, with one RNA molecule released per Rho hexamer in vitro. A
      simple RNA tracking model postulates that after Rho's initial binding, it
      translocates preferentially toward the 3' end of the RNA. Nitrocellulose filter
      binding studies combined with RNase H cleavage are inconsistent with this simple
      tracking model. Instead, they support a model in which Rho forms tight primary
      binding interactions with the recognition region of the RNA and remains bound
      there while transient secondary RNA binding interactions coupled to ATP
      hydrolysis serve to scan along the RNA to contact the RNA.DNA helix. This
      "tethered tracking" model is consistent with other properties of Rho factor,
      including the presence of two classes of RNA binding sites on the Rho hexamer and
      the 1:1 stoichiometry in the Rho helicase assay.

PMID- 7509072
TI  - Polioviruses containing picornavirus type 1 and/or type 2 internal ribosomal
      entry site elements: genetic hybrids and the expression of a foreign gene.
AB  - A picornavirus hybrid genome was constructed in which the internal ribosomal
      entry site (IRES) of encephalomyocarditis virus was inserted between the 5' non
      translated region and the open reading frame of poliovirus (PV), type 1
      (Mahoney). Upon transfection into HeLa cells, the hybrid RNA replicated and
      yielded a derivative of PV (W1-PNENPO). The PV IRES could be removed from
      pPNENPO, which resulted in a hybrid picornavirus (W1-P108ENPO) in which the
      translation of the PV open reading frame normally promoted by the type 1 IRES of
      PV was promoted by the type 2 IRES of encephalomyocarditis virus. This result
      indicates that these elements are not likely to contain cis-acting elements
      necessary for PV replication or encapsidation. A foreign gene (bacterial
      chloramphenicol acetyltransferase, CAT) was inserted into pPNENPO cDNA between
      the PV and encephalomyocarditis virus IRES elements. The dicistronic RNA
      replicated in HeLa cells and yielded a derivative of PV (W1-DICAT) with a genome
      17% longer than that of wild-type PV. CAT assays and immunoblot analyses showed
      that the viral RNA efficiently expressed the foreign gene in cell culture. The
      CAT activity diminished somewhat with each passage of the dicistronic virus, an
      observation which suggested that the inserted gene had a deleterious effect on
      viral replication. However, even after five virus passages, a significant
      quantity of the foreign gene was still expressed. Insertion of the open reading
      frame of luciferase (67 kDa) resulted in an RNA species that replicated and
      expressed luciferase for up to 20 hr after transfection. However, this elongated
      RNA was not encapsidated.

PMID- 7509073
TI  - Tityustoxin K alpha blocks voltage-gated noninactivating K+ channels and unblocks
      inactivating K+ channels blocked by alpha-dendrotoxin in synaptosomes.
AB  - Two nonhomologous polypeptide toxins, tityustoxin K alpha (TsTX-K alpha) and
      tityustoxin K beta (TsTX-K beta), purified from the venom of the Brazilian
      scorpion Tityus serrulatus, selectively block voltage-gated noninactivating K+
      channels in synaptosomes (IC50 values of 8 nM and 30 nM, respectively). In
      contrast, alpha-dendrotoxin (alpha-DTX) and charybdotoxin (ChTX) block voltage
      gated inactivating K+ channels in synaptosomes (IC50 values of 90 nM and 40 nM,
      respectively). We studied interactions among these toxins in 125I-alpha-DTX
      binding and 86Rb efflux experiments. Both TsTX-K alpha and ChTX completely
      displaced specifically bound 125I-alpha-DTX from synaptic membranes, but TsTX-K
      beta had no effect on bound alpha-DTX. TsTX-K alpha and TsTX-K beta blocked the
      same noninactivating component of 100 mM K(+)-stimulated 86Rb efflux in
      synaptosomes. Both alpha-DTX and ChTX blocked the same inactivating component of
      the K(+)-stimulated 86Rb efflux in synaptosomes. Both the inactivating and the
      noninactivating components of the 100 mM K(+)-stimulated 86Rb efflux were
      completely blocked when 200 nM TsTX-K beta and either 600 nM alpha-DTX or 200 nM
      ChTX were present. The effects of TsTX-K alpha and ChTX on 86Rb efflux were also
      additive. When TsTX-K alpha was added in the presence of alpha-DTX, however, only
      the noninactivating component of the K(+)-stimulated efflux was blocked. The
      inactivating component could then be blocked by ChTX, which is structurally
      homologous to TsTX-K alpha. We conclude that TsTX-K alpha unblocks the voltage
      gated inactivating K+ channels in synaptosomes when they are blocked by alpha
      DTX, but not when they are blocked by ChTX. TsTX-K alpha binds to a site on the
      inactivating K+ channel that does not occlude the pore; its binding apparently
      prevents alpha-DTX (7054 Da), but not ChTX (4300 Da), from blocking the pore. The
      effects of TsTX-K alpha on 125I-alpha-DTX binding and 86Rb efflux are mimicked by
      noxiustoxin, which is homologous to TsTX-K alpha and ChTX.

PMID- 7509075
TI  - Heterodimerization of epidermal growth factor receptor and wild-type or kinase
      deficient Neu: a mechanism of interreceptor kinase activation and
      transphosphorylation.
AB  - We have shown that members of the erbB family undergo homodimer and heterodimer
      formation. The rat p185c-neu and the epidermal growth factor receptor (EGFR) can
      associate into an active heterodimeric tyrosine kinase. Overexpression of these
      two receptors also results in a transformed phenotype. We now show that mutant
      Neu proteins resulting from a point mutation at the ATP-binding site (N757) or
      cytoplasmic domain deletions (N691stop) are still able to undergo EGF-induced
      heterodimerization with EGFR. Analysis of heterodimer formation between EGFR and
      truncated Neu proteins revealed that heterodimerization is preferred over
      homodimerization of EGFR. N757 can be transphosphorylated by associated EGFR upon
      EGF stimulation. However, the heterodimer composed of EGFR and N691stop is kinase
      inactive. These results provided evidence that the Neu ectodomain is sufficient
      to associate with EGFR physically, and the cytoplasmic domain interaction is
      required for heterodimeric kinase activation, indicating that Neu/c-erbB2 is not
      just a simple substrate for EGFR but a transactivator as well.

PMID- 7509074
TI  - Identification of an ion channel-forming motif in the primary structure of CFTR,
      the cystic fibrosis chloride channel.
AB  - Synthetic peptides with sequences representing putative transmembrane (M)
      segments of CFTR (the cystic fibrosis transmembrane conductance regulator) were
      used as tools to identify the involvement of such segments in forming the ionic
      pore of the CFTR Cl- channel. Peptides with sequences corresponding to M2 and M6
      form anion-selective channels after reconstitution in lipid bilayers. In
      contrast, peptides with the sequences of M1, M3, M4, and M5, or peptides of the
      same amino acid composition as M2 and M6 but with scrambled sequences, do not
      form channels. Conductive heterooligomers of M2 and M6 exhibit a single channel
      conductance of 8 pS (in 0.15 M KCl) and a 95% selectivity for anions over
      cations, properties that emulate both the conductance and the selectivity of the
      authentic CFTR channel. The identification of sequence-specific motifs that
      account for key functional attributes of the CFTR channel suggests that such
      modules may represent fundamental units of function and are plausible
      constituents of the pore-forming structure of the CFTR Cl- channel.

PMID- 7509077
TI  - Ultrasensitive retrovirus detection by a reverse transcriptase assay based on
      product enhancement.
AB  - Reverse transcriptase (RT) is an indispensable component of infectious
      retroviruses. We have developed an ultrasensitive RT test in which RNA of
      bacteriophage MS2 serves as the template for RT-mediated cDNA synthesis. A
      fragment of the cDNA is selectively amplified by polymerase chain reaction and
      the amplification product is analyzed by Southern blot hybridization or enzyme
      immunoassay. The procedure was 10(6) to 10(7) times more sensitive than a
      conventional RT test and detected as little as 10(-9) unit of murine leukemia
      virus RT, which corresponded to 2.1 x 10(2) molecules, a number present in 3-11
      virions. As a screening assay for filterable particle-associated RT, it was
      positive with supernatants from cell cultures producing human immunodeficiency
      virus (HIV) type 1 or human T-cell leukemia virus (HTLV) type 1 or 2, but was
      negative with nonproducer cultures. It was positive with plasma samples from all
      tested individuals infected with HIV-1, HIV-2, or HTLV-1 and sera from cats
      infected with feline leukemia virus or feline immunodeficiency virus. Control
      samples from blood donors or uninfected cats were negative. Density banding
      experiments with culture supernatants showed that the RT activity was associated
      with virus particles. The assay should detect all replication-competent
      retroviruses or similar agents. It may be used as a screening assay for such
      agents, for quantitation of the viral load, drug susceptibility testing of RT,
      and control of virus inactivation in biological products.

PMID- 7509076
TI  - Heparinase inhibits neovascularization.
AB  - Neovascularization is associated with the regulation of tissue development, wound
      healing, and tumor metastasis. A number of studies have focused on the role of
      heparin-like molecules in neovascularization; however, little is known about the
      role of heparin-degrading enzymes in neovascularization. We report here that the
      heparin-degrading enzymes, heparinases I and III, but not heparinase II,
      inhibited both neovascularization in vivo and proliferation of capillary
      endothelial cells mediated by basic fibroblast growth factor in vitro. We suggest
      that the role of heparinases in inhibition of neovascularization is through
      depletion of heparan sulfate receptors that are critical for growth factor
      mediated endothelial cell proliferation and hence neovascularization. The
      differences in the effects of the three heparinases on neovascularization could
      be due to different substrate specificities for the enzymes, influencing the
      availability of specific heparin fragments that modulate heparin-binding
      cytokines involved in angiogenesis.

PMID- 7509078
TI  - Induction of RNA-binding proteins in mammalian cells by DNA-damaging agents.
AB  - A technique to detect RNA-binding proteins (RBP) involving hybridization of RNA
      probe to proteins transferred to a membrane was used to study RBP in different
      mammalian cells and in cells after genotoxic stress. With this approach, up to 13
      proteins of different sizes were detected in crude nuclear extracts by using a
      viral RNA probe consisting of the trans-activation-responsive (TAR) element of
      human immunodeficiency virus type 1 (HIV-1). The TAR RNA probe contains a stem
      loop structure found in nascent HIV-1 transcripts. A G+C-rich probe with similar
      structure also bound to many of these RBP. Only a 102-kDa protein strongly bound
      to other RNA probes lacking this structure, while a probe with an A+U-rich stem
      loop structure fail to bind most RBP, thus indicating a RNA secondary structure
      preference. The expression of these RBP varied substantially in nine different
      human and hamster cell lines, with no detectable RBP in two human myeloid lines.
      Evidence for induction of these RBP was found in six of seven lines after
      treatment with DNA-damaging agents; UV radiation was the most effective agent. In
      Chinese hamster ovary cells, which showed the strongest response, all five RBP
      present in untreated cells rapidly increased in activity after UV irradiation,
      and eight additional RBP were detected. The induction of these RBP by DNA
      damaging agents indicates one or more possible roles for these proteins in the
      cellular response to genotoxic stress and in viral activation after such stress.

PMID- 7509079
TI  - Does the rapid response to cisplatin-based chemotherapy justify its use as
      primary treatment for intracranial germ-cell tumours?
AB  - We reviewed presentation, diagnostic problems and outcome of eight cases of
      primary intracranial germ-cell tumour (4 germinoma, 4 teratoma) treated with
      Cisplatin-based chemotherapy at our centre over the last ten years. Three
      patients received primary chemotherapy with Cisplatin-based regimens followed by
      radiotherapy for subsequent relapse, two were treated with a combination of
      chemotherapy and external radiotherapy, and three received chemotherapy for
      relapse after radiotherapy. The response to Cisplatin-based chemotherapy was
      rapid, with some patents exhibiting symptomatic improvement within 24 h. Four
      patients achieved complete remission within 21 days, and three of these have
      remained progression-free. Four patients in total have survived for 32 to 128+
      months. Six of seven patients tested pre-treatment had central diabetes insipidus
      and five had partial anterior pituitary failure. The endocrine deficit progressed
      in two, with no recovery in any patient. It is arguable that chemotherapy should
      be the primary therapy in all such cases diagnosed on the basis of tumour markers
      and imaging, with surgery and/or radiotherapy as later options. As these tumours
      are rare, such questions can only be answered by collaboration studies.

PMID- 7509080
TI  - Neurotransmitter receptors and ionic conductances regulating the activity of
      neurones in substantia nigra pars compacta and ventral tegmental area.

PMID- 7509081
TI  - Convergence of synaptic terminals from the striatum and the globus pallidus onto
      single neurones in the substantia nigra and the entopeduncular nucleus.

PMID- 7509082
TI  - Striatal and subthalamic afferents to the primate pallidum: interactions between
      two opposite chemospecific neuronal systems.

PMID- 7509083
TI  - Sequential interactions of the TCR with two distinct cytoplasmic tyrosine
      kinases.
AB  - The T cell antigen receptor (TCR) initiates signals by interacting with
      cytoplasmic protein tyrosine kinases (PTKs) through a 17-residue sequence motif
      [called the antigen recognition activation motif (ARAM)] that is contained in the
      TCR zeta and CD3 chains. TCR stimulation induces the tyrosine phosphorylation of
      several cellular substrates, including the ARAMs. Lck kinase activity is required
      for phosphorylation of two conserved tyrosine residues in an ARAM. This
      phosphorylation leads to the recruitment of a second cytoplasmic PTK, ZAP-70,
      through both of the ZAP-70 Src homology 2 domains and its phosphorylation. Thus,
      TCR signal transduction is initiated by the sequential interaction of two PTKs
      with TCR ARAMs.

PMID- 7509084
TI  - T cell deletion in high antigen dose therapy of autoimmune encephalomyelitis.
AB  - Encounters with antigen can stimulate T cells to become activated and
      proliferate, become nonresponsive to antigen, or to die. T cell death was shown
      to be a physiological response to interleukin-2-stimulated cell cycling and T
      cell receptor reengagement at high antigen doses. This feedback regulatory
      mechanism attenuates the immune response by deleting a portion of newly dividing,
      antigen-reactive T cells. This mechanism deleted autoreactive T cells and
      abrogated the clinical and pathological signs of autoimmune encephalomyelitis in
      mice after repetitive administration of myelin basic protein.

PMID- 7509085
TI  - Regeneration-induced accelerated rejection in reduced-size liver grafts.
AB  - Liver regenerative processes are associated with enhanced expression of
      alloantigens. Accordingly, we tested the hypothesis that such enhanced surface
      expression of alloantigens during regeneration of reduced-size liver grafts is
      associated with accelerated rejection. Our OLT model was LEW (RT1) to BN (RT1n),
      with donor liver resected by 50%. The study group consisted of reduced-size
      allografts. Control groups were syngeneic reduced-size isografts and full-size
      allografts. Reduced-size isograft recipients survived indefinitely. Both
      isografts and allografts regenerated to their prereduction size within 12 days.
      Recipients of reduced-size allografts died of accelerated rejection within 12.2
      +/- 0.8 days, significantly earlier than recipients receiving full-size
      allografts (36.2 +/- 4.1 days, P < 0.01). The accelerated rejection in the
      regenerating allografts was mediated both by cellular and humoral mechanisms,
      evidenced by earlier lymphocytic invasion of the graft, enhanced donor MHC class
      II expression, and the emergence of IgM antibodies, directed specifically against
      donor endothelial antigens. These data suggest that regeneration of reduced-size
      allografts is accompanied by accelerated cellularly and humorally mediated
      alloreactivity. Recipients of reduced-size allografts may, therefore, benefit
      from more potent immunosuppression during the period of active liver
      regeneration.

PMID- 7509086
TI  - Mediators of leukocyte activation play a role in disseminated intravascular
      coagulation during orthotopic liver transplantation.
AB  - Leukocytes play an important role in the development of disseminated
      intravascular coagulation (DIC). In the reperfusion phase of OLT a DIC-like
      situation has been described and has been held responsible for the high blood
      loss during this phase. We investigated the role of leukocytes in the
      pathogenesis of DIC in OLT by measuring the leukocytic mediators released upon
      activation (cathepsin B, elastase, TNF, neopterin) and the levels of thrombin
      antithrombin III (TAT) complexes, seen as markers of prothrombin activation.
      Arterial blood samples were taken at 10 different time points during and after
      OLT. Samples were also taken of the perfusate released from the liver graft vein
      during the flushing procedure before the reperfusion phase. Aprotinin was given
      as a continuous infusion (0.2-0.4 Mill. KIU/hr) and its plasma levels were
      determined. Significantly elevated levels of neopterin (15-fold; P < 0.01),
      cathepsin B (440-fold; P < 0.01) in the perfusate, as compared with the systemic
      circulation, as well as their significant increases in the early reperfusion
      phase suggested that they were released by the graft liver. This was paralleled
      by elevated levels of elastase (1.3-fold, P < 0.05), TNF (1.5-fold, P = NS), and
      TAT complexes (1.4-fold; P < 0.1) in the perfusate. Significant correlations
      could be identified between the parameters of leukocyte activation and TAT
      complexes, whereas no correlation was observed between any of the parameters
      investigated and the aprotinin levels. Our results strongly indicate a release of
      leukocytic mediators from the graft liver during its reperfusion which seems to
      be related to the parallely increased prothrombin activation. No correlation
      could be seen between levels of aprotinin and levels of leukocytic mediators.

PMID- 7509087
TI  - Development of techniques for obtaining monodispersed human islet cells.
AB  - The aim of this study was to develop techniques to obtain monodispersed, human
      islet cells in large quantities, since these constitute a potentially
      transplantable beta cell mass with which to treat established type 1 diabetes, as
      well as provide the most appropriate substrate for studying the immune
      pathogenesis of the disease. Human islets were isolated from the pancreas of
      beating-heart organ donors by collagenase digestion. Enzymatic (collagenase types
      II, IV, V, and XI, trypsin, DNAse, and hyaluronidase) and chemical (EDTA and
      EGTA) conditions were then used to find the optimum requirements for digestion of
      intact human islets into their constituent cells. The combination of trypsin with
      EDTA provided the highest yield of monodispersed islet cells (963 cells/islet)
      and highest viability (88%). DNAse with EGTA gave high yields (710 cells/islet)
      but viability was low (55%). Lower yields and viability were obtained using
      collagenase types II, IV, V, and XI (47-243 cells/islet; viability 45-62%),
      hyaluronidase (410 cells/islet; 75% viability), and EDTA alone (253 cells/islet;
      viability 43%). Human islet cells monodispersed using trypsin 0.125 mg/ml in 0.1
      mM EDTA retained an insulin secretory response to glucose, and had intact surface
      class I MHC molecules when analyzed immediately after digestion by flow
      cytofluorimetry. Our results indicate that functionally intact, single, human
      islet cells may be obtained in abundance, and provide a potential substrate for
      islet cell transplantation in the treatment of patients with type 1 diabetes.

PMID- 7509088
TI  - Hepatitis C virus infection and allogeneic bone marrow transplantation.
AB  - Serum antibodies to hepatitis C virus (HCV) were tested for inpatients undergoing
      allogeneic BMT to determine the risk of acquiring HCV infection and the role of
      HCV in posttransplant liver complications. The HCV seroconversion rate was
      evaluated according to the date of BMT and blood donor screening at the time.
      Anti-HCV antibodies (anti-HCV) were detected with a second-generation ELISA and
      confirmed with a second-generation radioimmunoblot assay. All patients received
      leukocyte-depleted blood products and most received apheresis platelet
      concentrates. One hundred twenty of 181 consecutive patients transplanted from
      January 1987 to December 1991 were anti-HCV-negative before BMT, had at least 6
      months of follow-up, and were thus evaluated for the seroconversion rate. Before
      screening for non-A, non-B hepatitis, 14% of the patients seroconverted to HCV
      (0.44% per unit transfused). After introduction of screening for alanine
      aminotransferase and antibodies to hepatitis B core antigen the risk of
      seroconversion was 4% per patient (0.26% per unit). When, in addition, blood was
      screened for anti-HCV the risk fell to 1.6% (0.03% per unit). Positive anti-HCV
      status before and after BMT was not predictive of veno-occlusive disease, liver
      graft-versus-host disease (GVHD), or death due to liver dysfunction. In contrast,
      the risk of chronic hepatitis was significantly increased.

PMID- 7509089
TI  - Rapamycin but not FK506 inhibits the proliferation of mononuclear phagocytes
      induced by colony-stimulating factors.
AB  - FK506, CsA, and rapamycin are potent inhibitors of T lymphocyte activation;
      relatively little is known of their effects on cells of the monocyte/macrophage
      lineage. Studies were undertaken to determine the effects of these drugs on the
      proliferative response of bone marrow-derived mononuclear phagocytes (BMMP) to
      CSFs. Rapamycin inhibited the proliferation of BMMP cultured in the presence of
      10% L cell-conditioned medium, used as a source of macrophage CSF. The inhibition
      by rapamycin was dose dependent and apparent at concentrations of 0.1 nM or
      greater. In a similar fashion, rapamycin inhibited the proliferation of BMMP
      stimulated by the recombinant forms of murine IL-3 and murine granulocyte
      macrophage CSF, and human macrophage CSF. In contrast, neither FK506 nor CsA at
      concentrations as high as 1000 nM diminished the proliferation of BMMP cultured
      under identical conditions. FK506, but not CsA, blocked the inhibitory effects of
      rapamycin on the response of BMMP to CSFs. In summary, these data indicate that
      rapamycin inhibits the proliferation of BMMP in response to CSFs. These results
      imply that patients receiving rapamycin, but not FK506 or CsA, may have an
      impaired ability to generate a functional mononuclear phagocyte population.

PMID- 7509090
TI  - Effect of asialofetuin on prolongation of skin allograft survival by donor bone
      marrow cells.
AB  - Survival of skin allografts made to antilymphocyte serum (ALS)-treated recipients
      is prolonged by posttransplant intravenous injection of donor strain bone marrow
      cells (BMC). If asialofetuin (ASF) is coinjected with the BMC, the prolonged
      graft survival is augmented (e.g., median survival time increased from 43 days to
      72 days by injection of ASF). We have confirmed that, like peanut agglutinin
      binding stem cells, the active BMC are at risk for hepatic sequestration after
      injection, possibly via hepatic asialoglycoprotein receptors. A fraction enriched
      for these active cells binds to liver sections in vitro and localizes to liver in
      vivo. This binding and localization can be partly inhibited by ASF. Although
      injected cells could also be found in the spleen, the beneficial effect of ASF
      could be demonstrated in previously splenectomized mice. Also, splenectomy 2 hr
      after BMC injection (without ASF) had little effect on the BMC-induced prolonged
      graft survival, while transfer of cells from the removed spleens to secondary ALS
      treated recipients did not transfer such prolongation. In contrast, transfer of
      BMC from primary, donor marrow-injected recipients did transfer graft-prolonging
      activity, especially if both primary and secondary recipients were ASF injected.
      Our results suggest that recipient marrow, but not spleen, is the site of short
      term localization of graft survival-prolonging BMC. Augmentation of allograft
      survival with ASF in ALS-treated recipients appears to result from the diversion
      of BMC away from a microenvironment not conducive to the expression of their
      graft-prolonging activity.

PMID- 7509091
TI  - Therapy with FK 506 in pediatric liver recipients.

PMID- 7509093
TI  - Improved hemodynamics and tissue oxygenation following pentafraction-based
      solution administration in brain-dead dogs.

PMID- 7509094
TI  - Orthotopic liver transplantation for glycogen storage disease type Ib--treatment
      with recombinant human granulocyte colony-stimulating factor.

PMID- 7509092
TI  - Myocardial effects of interleukin-2.

PMID- 7509096
TI  - Rapid cytodiagnosis of endoscopic biopsy specimens in gastrooesophageal
      malignancy.
AB  - Squash cytology has been used extensively in examining central nervous system
      lesions. Recently this technique has been employed in examining endoscopic biopsy
      specimens. This study was conducted to assess the diagnostic value of squash
      cytology of biopsy samples from gastrooesophageal malignancies, and to evaluate
      the efficacy of Leishman's stain for rapid cytologic evaluation of squash
      preparations. One hundred and fifty five patients with oesophageal or gastric
      malignancy were subjected to endoscopic biopsy. The first biopsy specimen from
      each patient was crushed between two glass slides for cytologic evaluation. The
      smears were stained with Leishman's and Papanicolaou's stains. The results of
      squash cytology were then compared with histopathology. A positive diagnosis of
      malignancy was obtained by histology in 146 cases (94.2%) and by squash cytology
      in 141 cases (90.9%), by both Leishman's and Papanicolaou's staining. In 12 cases
      (7%) cytology revealed 'suspicious cells'. Histology plus squash cytology
      together gave a positive yield in 153 cases (98.7%). In 7 cases (4.5%) although
      squash cytology was positive for malignancy, hispathologic study failed to reveal
      malignancy. Squash cytology is a useful adjunct to conventional endoscopic biopsy
      for gastrooesophageal malignancy. This technique which does not require any
      additional effort or equipment may add to the diagnostic yield besides expediting
      the workup. Leishman's staining, which is simple, quick and inexpensive is as
      efficacious as Papanicolaou's method for squash cytology.

PMID- 7509095
TI  - Pediatric kidney transplantation at the University of Pittsburgh.

PMID- 7509097
TI  - Variabilities in the antigenic structure of persisting tick-borne encephalitis
      virus strains.
AB  - Antigenic variants in the E protein from persisting tick-borne encephalitis (TBE)
      virus strains were analyzed using monoclonal antibodies (MAbs) to an analogous
      protein of the reference Sofyin strain. MAbs to sequential epitopes demonstrated
      their ability to differentiate persisting TBE virus strains from Sofyin and from
      each other. Two MAbs (2H3 and 13D6) showed a higher neutralizing activity in the
      interaction with persisting TBE virus variants as compared to the Sofyin strain.
      Based on the obtained data, a comparison was made of topologically identical
      epitopes from the E protein of reference and persisting virus strains. The
      possibility of increasing the neutralizing activity of MAbs through alterations
      in the primary structure of sequential antigenic sites is discussed.

PMID- 7509100
TI  - Efficacy of insulin-like growth factor binding protein 3 in predicting the growth
      hormone response to provocative testing in children treated with cranial
      irradiation.
AB  - Recent data suggest that the plasma concentration of insulin-like growth factor
      binding protein 3 (IGFBP-3) is useful as a screening test for growth hormone (GH)
      deficiency. In this study, we measured by radioimmunoassay the levels of IGFBP-3
      in a group of 20 subjects (12 males) of 5 years and 7 months to 16 years of age
      undergoing standard GH testing following cranial irradiation. The patients had
      received 1800 to > 6000 cGY of radiation to the hypothalamic-pituitary region, a
      median of 2.7 years (range 2-7 years) prior to testing. The IGFBP-3
      concentrations were discordant with the results of GH testing 60% (12/20) of the
      time. Although IGFBP-3 levels were below the mean for age in 14 of 15 GH
      deficient (peak GH < 10 micrograms/l) patients, only three of 15 GH-deficient
      patients had IGFBP-3 concentrations that fell below age-adjusted norms. In
      contrast, the IGFBP-3 levels were within the normal range in all five patients
      with normal GH responses. The low sensitivity (20%) of IGFBP-3 in predicting the
      subjects with abnormal responses was not improved by adjusting the values for
      bone age or stage of puberty. We concluded that a single plasma determination of
      IGFBP-3 is not a useful screening test for GH deficiency among patients
      previously treated with cranial irradiation.

PMID- 7509099
TI  - Dermatophytes and keratin in patients with hereditary palmoplantar keratoderma. A
      mycological study.
AB  - Fourteen patients with hereditary palmoplantar keratoderma of the Unna Thost
      variety were included in the study. Dermatophytosis was found in 7 of the 14
      patients. Six were affected with T. rubrum and one with T. mentagrophytes. The
      growth pattern of dermatophytes in keratin from the patients did not differ from
      that of normal control individuals. Keratin from patients with hereditary
      palmoplantar keratoderma was sterilized with ethylene gas and placed in the
      center of culture plates, previously broad inoculated with control dermatophytes
      or dermatophytes isolated from patients. An inhibition zone around the keratin
      was found in 42.9% of the control dermatophytes and in 83.4% of the patient
      cultures. The inhibition zone was only seen in cultures with T. rubrum and not in
      those with T. mentagrophytes. No significant difference in minimal inhibitory
      concentration values against ketoconazole between control dermatophytes and
      dermatophytes from patients was demonstrated.

PMID- 7509098
TI  - Fluorescent staining with bromocresol purple: a rapid method for determining
      yeast cell dead count developed as an assay of killer toxin activity.
AB  - A method is described for detecting yeast cells with plasma membrane damage,
      based on cell staining with bromocresol purple (BCP) which has a convenient
      fluorescence after entering the cells at pH below 5.2. The method was used to
      determine the activity of Saccharomyces cerevisiae pore-forming killer toxin K1
      in commonly used lethal units. The BCP test is rapid and as precise as the
      plating test.

PMID- 7509102
TI  - Localization of Cu/Zn and Mn superoxide dismutase in various thyroid disorders.
AB  - The intracellular localization of Cu/Zn- and Mn-superoxide dismutase (SOD), which
      catalyze the dismutation of superoxide radicals (O2-) to O2 and H2O2, was studied
      in the thyroid tissue of various thyroid disorders by an immunohistochemical
      technique. The concentrations of both SODs in those tissues were measured also by
      a sandwich enzyme immunoassay technique. Copper/zinc-SOD in thyroid tissues were
      identified by immunocytochemical staining in most cases of papillary carcinoma
      and in some cases of other thyroid disorders. In normal follicular cells this
      enzyme is localized in the perinuclear cytoplasm, whereas in thyroid tumor or
      hyperplastic follicular cells it exists homogeneously in cytoplasm. Manganese-SOD
      stained strongly in papillary carcinoma and papillary-growing cells in the
      thyroid tissue of adenoma and Graves' disease. The concentrations of Cu/Zn-and Mn
      SOD in thyroid tumor tissues and hyperplastic follicular disorders were
      significantly higher than those in normal thyroid tissue when they were compared
      as a function of protein or deoxyribonucleic acid contents. The ratio of Mn-SOD
      to Cu/Zn-SOD was significantly higher only in papillary carcinoma, except for
      other thyroid disorders as compared with that in the normal thyroid. In
      conclusion, SOD seems to be related to cell proliferation and differentiation in
      the thyroid follicular cell because Cu/Zn-SOD changes its localization in tumor
      and hyperplastic follicular cells and because the Mn-SOD concentration is
      increased in papillary carcinoma or papillary-growing cells.

PMID- 7509103
TI  - FK506 inhibits phytohemagglutinin-, but not interferon-gamma-, induced HLA-DR
      antigen expression and accessory cell function on primary cultured human thyroid
      cells.
AB  - We investigated the effects of FK506, a novel immunosuppressive agent, on the
      phytohemagglutinin (PHA) or interferon-gamma (IFN-gamma)-induced expression of
      HLA-DR antigen, accessory cell function and proliferation of primary cultured
      human thyroid cells. Primary cultured thyroid cells from patients with Graves'
      disease were incubated for 3 days with PHA in concentrations in the range 1-50
      mg/l or with 200 kU/l of IFN-gamma, in the presence or absence of FK506. The
      surface expression of HLA-DR antigen was measured by flow cytometry. Accessory
      cell function of thyroid cells was assessed by the incorporation of [3H]thymidine
      to T cells in the presence of 0.1-1.0 micrograms/l staphylococcus enterotoxin B
      (SEB). The proliferation of thyroid cells was determined from [3H]thymidine
      incorporation assays. FK506 inhibited the induction of HLA-DR antigen expression
      by PHA on thyroid cells in a dose-dependent manner, but did not inhibit that by
      IFN-gamma. Polyclonal anti-IFN-gamma antibody partly inhibited the PHA-induced
      HLA-DR antigen expression on thyroid cells. Phytohemagglutinin enhanced the SEB
      mediated accessory cell function of thyroid cells. FK506 inhibited the accessory
      cell function induced by PHA. FK506 alone did not directly affect the thyroid
      cell proliferation, although it ameliorated the thyroid cell growth suppressed by
      PHA. Our data suggest that FK506 suppresses the HLA-DR antigen expression induced
      by PHA and the subsequent accessory cell function on thyroid cells via the
      inhibition of T lymphocytes present in the primary culture.

PMID- 7509104
TI  - Structure of the vitreoretinal border region in spontaneously diabetic BB rats.
AB  - The morphology of the vitreoretinal border region, also termed the inner limiting
      membrane, was examined in spontaneously diabetic rats (BB rats), in non-diabetes
      prone rats (WB rats) and in Buffalo rats (BUF rats) by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). This was performed
      in order to visualize a possible increase in thickness of the lamina densa or in
      the whole vitreoretinal border region complex with duration of diabetes. The
      median thickness of the lamina densa in the three groups varied between 34 and 68
      nm. In BB rats the thickness decreased with age and duration of diabetes. In WB
      rats the lamina densa thickened up to the 9th month and then decreased to the
      level of the young rats. In BUF rats the lamina densa decreased in thickness with
      age. The median thickness of the whole vitreoretinal border region varied
      between: BB rats: 84 and 126 nm (SEM) and 68 and 119 nm (TEM); WB rats: 42 and 84
      nm (SEM) and 51 and 68 nm (TEM); BUF rats: 42 nm (SEM) and 34 and 68 nm (TEM). In
      BB rats the whole vitreoretinal border region appeared in SEM to thicken with
      duration of diabetes > or = 27 weeks, whereas in TEM no specific pattern could be
      statistically demonstrated. In WB rats the whole vitreoretinal border region was
      thinner in 3-month-old animals than in 9-month-old animals in (SEM) and TEM. In
      BUF rats there was no difference in thickness between young and older animals.
      Light microscopy of older diabetic animals showed neovascularization of the iris
      stroma.

PMID- 7509105
TI  - Immunohistochemical detection of breast specific antigens and cytokeratins in
      metastatic breast carcinoma in the liver.
AB  - The present study was performed to evaluate the diagnostic reliability of
      antibodies to breast carcinoma-specific antigen and antibodies to cytokeratin
      catalogue in a metastatic hepatic lesion. Immunohistochemical examinations using
      antibodies to gross cystic disease fluid protein-15 (GCDFP-15), BCA-225 (a
      glycoprotein secreted by T47D breast carcinoma cell line) and BRST-5 (a
      glycoprotein identified in SK-BR-7 breast carcinoma cell line), anti-cytokeratin
      monoclonal antibodies of MA904, AE3, CAM5.2, PKK1 and cytokeratin 19, and
      polyclonal anti-keratin antibodies were done. These were on 15 cases of primary
      breast carcinoma, eight cases of metastatic breast carcinoma in the liver, five
      cases of cholangiocarcinoma, eight cases of hepatocellular carcinoma and 11 cases
      of metastatic adenocarcinoma of another primary tumor in the liver. Results
      showed that GCDFP-15 antigen was most reliable: it was 100% positive in both
      primary and metastatic breast carcinomas unrelated to histological subtypes, and
      100% negative in primary or other metastatic carcinomas in the liver. BCA-225
      antigen was detected in high amounts in breast carcinomas (100%, 23/23), but it
      was positive in cholangiocarcinomas (80%, 4/5) and another metastatic carcinoma
      in the liver (64%, 7/11). BRST-5 was specifically positive in breast carcinomas
      but the positivity was low (13%, 3/23). Cytokeratin 19 and keratin were useful to
      discriminate hepatocellular carcinomas (0%, 0/8) from breast carcinomas (87%,
      20/23; 96%, 22/23), but they were also positive in cholangiocarcinomas (100%,
      5/5) and other metastatic carcinomas in the liver (91%, 10/11).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7509101
TI  - Production of alpha-subunit of glycoprotein hormones by pituitary somatotroph
      adenomas in vitro.
AB  - Somatotroph adenomas of the pituitary secrete growth hormone in excess and are
      associated with acromegaly. Morphologically, they can be separated into two
      entities, densely and sparsely granulated variants. It has been shown that a
      number of somatotroph adenomas produce alpha-subunit of glycoprotein hormones;
      however, it is not clear whether alpha-subunit production correlates with tumor
      cell morphology. We studied 32 surgically removed pituitary somatotroph adenomas
      in tissue culture to determine structure-function correlations of growth hormone
      and alpha-subunit production. All tumors were classified on the basis of detailed
      histological, immunocytochemical and electron-microscopic studies. Fifteen tumors
      were densely granulated and 17 were sparsely granulated. In addition to growth
      hormone, all 15 densely granulated tumors released alpha-subunit in vitro,
      whereas of the 17 sparsely granulated tumors only 4 released alpha-subunit;
      moreover, the mean baseline levels of alpha-subunit were significantly higher in
      densely granulated adenomas than in sparsely granulated adenomas. Parallel
      response of release of both hormones was found during stimulation with growth
      hormone-releasing hormone or thyrotropin-releasing hormone and during suppression
      with somatostatin or bromocriptine in densely granulated tumors. alpha-subunit
      response to stimulation or suppression could not be determined with significance
      in sparsely granulated tumors because of low basal levels. The results indicate
      that alpha-subunit production and release is characteristic of densely granulated
      somatotroph adenomas and that alpha-subunit is coregulated with growth hormone by
      adenohypophysiotropic substances; in contrast, alpha-subunit production, by
      sparsely granulated somatotroph adenomas is rare and, when present, much lower in
      quantity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509106
TI  - Immunohistochemical comparison between anaplastic seminoma and typical seminoma.
AB  - In order to study the possible biological differences between anaplastic and
      typical seminoma, the following factors were studied in 11 cases of anaplastic
      seminoma and 15 cases of typical seminoma: mitotic activity, proliferating cell
      nuclear antigen (PCNA) expression, immunohistochemical analyses for cytokeratin,
      vimentin, placental alkaline phosphatase (PLAP), beta-human chorionic
      gonadotropin (beta-hCG), alpha-fetoprotein (AFP) and c-myc oncoprotein.
      Anaplastic seminoma was classified according to Mostofi's criteria, which is
      primarily based on the mitotic activity of the tumor. Mitotic activity was
      evaluated by both mitotic count and rate. Statistically significant correlations
      were observed between mitotic count and mitotic rate (R = 0.891), and between the
      mitotic count and PCNA labeling index (R = 0.792), in both typical and anaplastic
      seminomas. Immunostaining patterns for cytokeratin, vimentin, PLAP, beta-hCG, AFP
      and c-myc oncoprotein were not significantly different between typical and
      anaplastic seminoma. The present data indicated that no apparent
      clinicopathologic and immunohistochemical parameters discerning anaplastic
      seminoma from typical seminoma were present, when identifying anaplastic seminoma
      on the basis of high mitotic count. Anaplastic seminoma may therefore simply
      represent seminoma with high proliferative activity.

PMID- 7509107
TI  - DSP-4 lesion of locus coeruleus does not affect spontaneous predatory behaviour
      in cats.
AB  - The effect of the destruction of locus coeruleus noradrenergic (LC NA) projection
      on spontaneous predatory attack, predatory competition and food intake was
      studied in cats. Selective noradrenergic neurotoxin DSP-4 injected into LC caused
      71% decrease of noradrenaline content in amygdala and 41% decrease in
      hypothalamus. Predatory behaviour, predatory competition as well as food intake
      remained unchanged. It is concluded that LC NA projection is specifically
      involved neither in predation nor in food intake, which is in agreement with
      recent electrophysiological data.

PMID- 7509108
TI  - A method for determination of energetical structure of conformational states of
      voltage dependent ionic channels.
AB  - The mechanism of state transitions has been applied as a base to investigate
      energetical structure of conformational states of ionic channels. The kinetics of
      transitions between conformational states, governing the dynamics of the action
      potential, was represented in the form of a matrix equation. Transition
      coefficients have been expanded as a function of the external potential to
      provide a set of parameters. Resulting theoretical equations have been
      incorporated into the Hodgkin-Huxley model of the action potential. Model
      parameters, related to energy levels and barriers between conformational states,
      can be evaluated by fitting a theoretical curve to the experimental one.

PMID- 7509109
TI  - Luminescent/paramagnetic probes of order and orientation in biological
      assemblies: the transformation of luminescent probes into pi-radicals by
      photochemical reduction within the contractile apparatus.
AB  - Several unsubstituted xanthene dyes (eosin, erythrosin, and fluorescein) were
      irradiated by laser light at their absorption maximum in the presence of
      different reducing agents. Due to photochemical reduction the quinoidal structure
      of the xanthene ring is transformed into a semiquinone and a pi-radical is formed
      having a characteristic electron paramagnetic resonance (EPR) signal of an
      unpaired electron spin with proton hyperfine interactions. A strong EPR signal is
      observed from the dye in solution or when specifically attached to myosin
      following irradiation in the presence of dithiothreitol or cysteine. The
      spectroscopic methods of fluorescence polarization and EPR are useful in the
      study of ordered biological assemblies. These methods generate complementary
      information about the order of the system but a consistent quantitative
      interpretation of the related data is complicated because the signals arise from
      different donors. Our method allows us to detect both signals from the same
      donor. We applied our new technique to the study of skeletal muscle fibers. The
      fluorescent dye iodoacetamidofluorescein was covalently attached to the reactive
      thiol of the myosin molecule in muscle fibers. Fluorescence polarization and EPR
      spectroscopy were performed on the labeled fibers in rigor. Both signals indicate
      a highly ordered system characteristic of cross-bridges bound to actin.

PMID- 7509110
TI  - Carotid body neurotransmission.

PMID- 7509112
TI  - Role of substance P in rat carotid body responses to hypoxia and capsaicin.

PMID- 7509111
TI  - Neurochemical and molecular biological aspects on the resetting of the arterial
      chemoreceptors in the newborn rat.

PMID- 7509113
TI  - Neurotransmitters and second messenger systems in the carotid body.

PMID- 7509114
TI  - Light-and electronmicroscopical immunohistochemical investigation of the
      innervation of the human carotid body.

PMID- 7509115
TI  - Serotonin (5-hydroxytryptamine) expression in pulmonary neuroendocrine cells (NE)
      and a netumor cell line.

PMID- 7509116
TI  - [HTLV-I and retinal antigen recognized by T cells].
AB  - MT-2 immune but not naive murine (B10.BR) spleen cells responded not only to HTLV
      I-infected cell lines but also to retinal antigens of various species by antigen
      induced cell proliferation. The phenotype of the responding cells against HTLV-I
      infected cell lines as well as retinal antigens was Thy-1.2+, CD4+ and CD8-. The
      antigen-induced cell proliferation against both HTLV-I-infected cell lines and
      retinal antigens was clearly inhibited by monoclonal antibodies to CD3, CD4, and
      MHC class II (I-AK). These data indicate that an epitope of HTLV-I-infected cell
      lines recognized by the CD4+ T cell is crossreactive to that of retinal antigens.

PMID- 7509117
TI  - [Neovascularization in experimental retinal venous obstruction in rabbit].
AB  - Experimental retinal venous obstruction was produced in rabbit eyes by
      transadventitial instillation of thrombin for the purpose of studying the late
      stage of histopathological changes in the retina. Three months after the
      instillation, abnormal vessels and compensatory shunt vessels were observed by
      ophthalmoscopy. Capillary obstruction, blood leakage from venules and
      neovascularization were observed on gelatin-fluorescein injected flat
      preparations of the retina three months after the thrombus formation. Although
      venular lumina were first narrowed and restored to normal three months after
      thrombin instillation, the lumina of arterioles remained narrow and intraluminal
      fibrin thrombi were present in the arterioles more than three months later in
      light microscopy. In electron microscopy many ribosomes and large nuclei were
      observed in newly formed retinal vessels, and their basement membranes were thin
      and discontinuous. Ghost vessels penetrated by glial cell processes were also
      found in the proliferative tissues. These results suggest that neovascularization
      occurs when the intraretinal damages last more than 3 months after the onset of
      thrombogenesis.

PMID- 7509118
TI  - [Endorectal magnetic resonance imaging of the prostate and bladder].
AB  - Endorectal magnetic resonance imaging (MRI) using an endorectal surface coil has
      been evaluated basically and clinically. This new modality obtained increased
      resolution magnetic resonance images of the pathologic conditions of the prostate
      and bladder. Compared with images obtained with a body coil, the surface coil
      images clearly demonstrate prostatic intraglandular zonal anatomy. The clear
      images of prostatic capsule and neurovascular bundle seen on the surface coil may
      contribute to the local staging of prostate cancer. The staging diagnosis of
      bladder tumor located in the bladder neck will be the best candidate for
      endorectal MRI. Enhancement with gadolinium may improve the ability to
      differentiate superficial from deep bladder-wall tumors. We concluded that
      endorectal MRI is safely performed and is extremely useful for the local staging
      of prostate cancer and bladder neck tumor. Further studies will be required to
      evaluate the clinical significance of this new modality.

PMID- 7509119
TI  - [Clinical evaluation of intracavernous self-injection of vasoactive drugs for
      impotence: a long-term follow-up observation].
AB  - From December 1989 to September 1992, nine patients with impotence were
      instructed to perform intracavernous self-injection of vasoactive drugs. At first
      40 mg of papaverine hydrochloride was used in all patients and the response on
      erection was evaluated. If the response did not show sufficiently functional
      erection, a mixture of 40 mg of papaverine hydrochloride and 1 mg of phentolamine
      mesylate or 20 mg of prostaglandin E1 was reinjected. Eight patients had achieved
      full erections and vaginal penetrations without noteworthy complications during
      the follow-up period. Out of eight patients, three patients were able to
      ejaculate and one patient showed recovery of erection. No major side effects were
      seen. In conclusion, intracavernous self-injection is a useful modality for
      impotence.

PMID- 7509120
TI  - [Clinical effect of midodrine hydrochloride on the patients with urinary
      incontinence].
AB  - The effects of midodrine hydrochloride (Brand name: Metligine tablet 2 mg,
      Manufacturer: Taisho Pharmaceutical Co., Ltd.), alpha-1 adrenalin receptor
      agonist against urinary incontinence was examined on 5 female patients with
      stress urinary incontinence and 5 male urinary incontinent patients of various
      causes. Metligine was administered in the dose of 4 mg daily for 2 to 4 weeks.
      Eighty per cent of the stress incontinent patients showed improvement and five
      incontinent male also showed improvement of symptoms. No side effects were
      recognized.

PMID- 7509122
TI  - Inducible ventricular tachyarrhythmia in children with Wolff-Parkinson-White
      syndrome.

PMID- 7509121
TI  - Response to sotalol predicts the response to amiodarone during serial drug
      testing in patients with sustained ventricular tachycardia and coronary artery
      disease.
AB  - It was analyzed whether the response to sotalol can predict the response to
      amiodarone as evaluated by programmed ventricular stimulation in 30 patients with
      coronary artery disease and documented recurrent sustained ventricular
      tachycardia (VT). Programmed ventricular stimulation was performed using 1 or 2
      extrastimuli during sinus rhythm and 4 drive cycle lengths at 2 right ventricular
      sites. If no ventricular tachyarrhythmia was induced, a third extrastimulus was
      introduced during a paced cycle length of 500 ms. During the control study, VT
      (mean cycle length 305 +/- 63 ms) was induced in all patients, and the right
      ventricular effective refractory period (during S1-S1 = 500 ms) was 223 +/- 12
      ms. After sotalol, sustained and nonsustained VT were inducible in 22 (73%) and 7
      (23%) patients, respectively. One patient did not undergo stimulation on sotalol,
      because of side effects. After amiodarone, sustained and nonsustained VT were
      inducible in 23 (77%) and 7 (23%) patients, respectively. The mean cycle length
      of the induced VT was prolonged after both drugs by 17% (p < 0.001). The
      effective refractory period was prolonged by 15% (p < 0.001) after sotalol and by
      13% (p < 0.001 compared with baseline study; p = NS between both drugs) after
      amiodarone. Thus, concordant results (effective or ineffective drug) between
      sotalol and amiodarone were found in 26 patients (87%). IN CONCLUSION: (1) The
      effects of sotalol and amiodarone on the cycle length of induced VT and on right
      ventricular effective refractory period were similar; and (2) inability to
      suppress VT by amiodarone can be predicted from the response to sotalol.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7509123
TI  - Interferon treatment of chronic hepatitis C.
AB  - The natural history of chronic hepatitis C is just beginning to be clarified,
      with its more common course being an insidiously progressive liver disease that
      often remains clinically inconsequential for many years or even decades. Although
      chronic hepatitis C progresses histologically, the impact on the clinical well
      being of the patient is less evident. Interferon is an effective therapy for this
      disease because of its antiviral effect on the cytopathic hepatitis C virus,
      lowering serum alanine aminotransferase (ALT) levels, rather than because of any
      immune modulatory mechanism. Unfortunately, interferon therapy does not
      permanently eradicate hepatitis C virus in the majority of patients, and relapse
      with return of the serum ALT level to the pretreatment range occurs in
      approximately 70% of responding patients. Other interferon-treated patients
      continue to be viremic and are not considered to be responders. In addition, not
      all patients with chronic hepatitis C require treatment. A systematic approach to
      patient evaluation is necessary to determine the need for treatment, assess
      treatment response, identify side effects of therapy, and assist in other
      clinical decisions.

PMID- 7509125
TI  - Early brain trauma and schizophrenia in Nigerian patients.
AB  - OBJECTIVE: A number of reports have suggested that early brain trauma, especially
      obstetric complications, may be associated with schizophrenia. This observation
      seems at variance with the similar rates of schizophrenia reported for advanced
      and developing countries when viewed against the high rate of perinatal morbidity
      in developing countries. Using patients with mania as comparison subjects, the
      authors investigated the association of early brain trauma with schizophrenia in
      adult life among Nigerian patients. METHOD: The manic (N = 12) and schizophrenic
      (N = 26) groups, both diagnosed according to the Research Diagnostic Criteria,
      were compared in respect to the prevalence of events commonly regarded as
      definite obstetric complications and the prevalence of childhood brain injury for
      which hospitalization was required. RESULTS: A history of early brain trauma was
      associated with an adult diagnosis of schizophrenia. Schizophrenic patients with
      a history of early brain trauma were more likely than those without early brain
      trauma to have shown poor scholastic performance in childhood. They also showed
      mixed cerebral laterality in adulthood. CONCLUSIONS: Early brain trauma may be a
      specific risk factor for the later development of schizophrenia. Patients with
      such a history may evidence other features of neurodevelopmental deviance.

PMID- 7509124
TI  - Mixed cryoglobulinemia and hepatitis C virus.
AB  - BACKGROUND: Mixed cryoglobulinemia (MC) is frequently associated with clinical
      and biological evidence of liver disease and has recently been reported in cases
      of hepatitis C virus (HCV) infection. The aim of this study was to assess
      prospectively in a large series of MC patients: (1) the prevalence of HCV markers
      (anti-HCV antibodies and HCV RNA in serum and cryoprecipitate); (2) the main
      clinical, biologic and liver histologic features in patients with or without HCV
      infection. PATIENTS: One hundred fifteen consecutive unselected MC patients were
      studied: 45% had well-defined underlying diseases ("nonessential" MC). Fifty-five
      percent with no cause of MC were considered to have "essential" MC and were
      subjected to in-depth examination. METHODS: Patients were considered to have MC
      if two successive determinations of their serum cryoglobulin level were above
      0.05 g/L. Anti-HCV antibodies (Ab) were detected in all patients by second
      generation tests (ELISA, RIBA). We also looked for HCV RNA sequences amplified by
      polymerase chain reaction (PCR) in the sera and cryoprecipitates of 39 patients;
      HBs antigen, anti-HBs Ab and anti-HBc Ab in all patients; and HBV DNA in 20 sera
      and 17 cryoprecipitates. Quantitative HCV Ab and RNA studies were performed on
      whole serum, cryoprecipitates, and supernatants. Clinical features were recorded
      retrospectively for each patient. Liver biopsies from 23 anti-HCV Ab-positive and
      7 anti-HCV Ab-negative patients were examined histologically, with qualitative
      and quantitative analysis. RESULTS: Anti-HCV Ab were found in 47/115 (41%)
      patients by ELISA and RIBA: 33/63 (52%) essential MC and 14/52 (27%) nonessential
      MC. Among the 63 essential MC patients, the 33 anti-HCV Ab-positive (Group 1)
      were compared to the 30 anti-HCV Ab-negative patients (Group 2). Group 1 patients
      had more cutaneous involvement (Raynaud's phenomenon, purpura, livedo, distal
      ulcers, or gangrenous changes) (17 versus 5: p = 0.004), higher alanine
      aminotransferase levels (110 +/- 22 versus 41 +/- 10 IU; p < 0.005), higher serum
      cryoglobulin levels (0.35 +/- 0.07 versus 0.12 +/- 0.04 g/L; p = 0.01), lower
      CH50 (28 +/- 3 versus 44 +/- 2 CH50/mL; p = 0.0001) and lower C4 levels (0.20 +/-
      0.02 versus 0.29 +/- 0.03 g/L; p < 0.04). The prevalence of HBV serum markers was
      low in both groups, and HBV DNA was never detected in any of the sera and
      cryoprecipitates tested. HCV RNA sequences were detected in 10/16 (63%) sera and
      12/16 (75%) cryoprecipitates from Group 1 patients, whereas they were not in the
      sera or cryoprecipitates from 23 Group 2 patients. Using quantitative PCR, HCV
      RNA in cryoprecipitates was concentrated 20 to 100 times despite the absence of
      significant anti-HCV Ab concentration in these samples. Histologic examination of
      liver biopsies revealed a spectrum of lesions ranging from chronic active
      hepatitis to cirrhosis, but Knodell's score did not differ between the groups.
      CONCLUSION: (1) About 50% of the essential MC patients had anti-HCV Ab, and these
      patients had more severe cryoglobulinemia-associated clinical and biological
      signs; (2) HCV RNA sequences were found in the large majority of sera and
      cryoprecipitates from patients with essential MC and anti-HCV Ab and were more
      concentrated in cryoprecipitates than in supernatants. These results suggest a
      role for HCV in the pathogenesis of MC and indicate that many cases of essential
      MC may be secondary to HCV infection and thus nonessential.

PMID- 7509127
TI  - Spectrophotometric method for the assay of glycosaminoglycans and
      glycosaminoglycan-depolymerizing enzymes.
AB  - Undegraded glycosaminoglycans form a complex with 1-ethyl-2-[3-(1-ethylnaphtho
      [1,2-d]thiazolin-2-ylidene)-2- methylpropenyl]naphtho-[1,2-d]thiazolium bromide
      (Stains-all) in solution resulting in a characteristic shift in spectrum.
      Hyaluronic acid (a nonsulfated glycosaminoglycan) reacts with the dye to form a
      complex with an absorbance maximum at 650 nm, while sulfated glycosaminoglycans
      (chondroitin sulfates A and C, dermatan sulfate, keratan sulfate, and heparan
      sulfate) give rise to an increase in absorbance at 480 nm. Increases in
      absorbance at the appropriate wavelength are directly proportional to the
      concentration of glycosaminoglycan interacting with the dye. This phenomenon
      provided the basis for a sensitive spectrophotometric assay for the quantitative
      measurement of bacterial and mammalian glycosaminoglycan-depolymerizing enzymes.
      The basic assay method was adapted for use in 96-well microtiter trays, thus
      enabling large numbers of assays to be carried out simultaneously.

PMID- 7509126
TI  - Noradrenergic activity and prediction of psychotic relapse following haloperidol
      withdrawal in schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to develop a model based on the authors'
      previous studies to identify which neuroleptic-treated schizophrenic patients are
      at risk of early relapse following drug withdrawal. METHOD: Clinical and CSF
      monoamine-related variables obtained for 50 male haloperidol-treated,
      schizophrenic patients were used in a logistic regression model to identify those
      who relapsed (N = 24) within 6 weeks after placebo substitution and those who did
      not (N = 26). RESULTS: The oral dose of haloperidol, weight, CSF norepinephrine,
      3-methoxy-4-hydroxyphenylglycol and chromogranin A-like immunoreactivity, and the
      anxiety and paranoia subscale ratings of the Brief Psychiatric Rating Scale
      produced a model that correctly predicted 18 relapsers and 21 nonrelapsers. By
      including the interactions of paranoia subscale by CSF norepinephrine and anxiety
      by CSF norepinephrine, the model correctly identified 20 relapsers and 23
      nonrelapsers with a sensitivity and specificity of 83% and 88%, respectively.
      CONCLUSIONS: Increased noradrenergic activity during chronic dopamine blockade
      may be an episode marker and may predict relapse within 6 weeks following
      haloperidol withdrawal in schizophrenia. Effective relapse prediction models have
      important practical implications for the treatment of schizophrenia and the
      understanding of the psychotic relapse process.

PMID- 7509128
TI  - [Nutritional and defunctionalized jejunostomy in the chemotherapeutic treatment
      of gastric non-Hodgkin's lymphoma. Preliminary experience].
AB  - The authors propose a jejunostomy on an omega loop distal to the Treitz ligament
      as a treatment for unresectable gastric lymphomas. The rationale is to provide
      nutritional support during chemotherapy in a situation when the stomach is
      defunctionalised. As assessed by clinical, morphological and biological
      parameters, the association of chemotherapy and jejunostomy may represent a valid
      therapeutical strategy for patients considered unresectable.

PMID- 7509130
TI  - Cyclooxygenase gene expression in inflammation and angiogenesis.

PMID- 7509129
TI  - Brequinar sodium, mycophenolic acid, and cyclosporin A inhibit different stages
      of IL-4- or IL-13-induced human IgG4 and IgE production in vitro.
AB  - We investigated the effect of cyclosporin A (CsA), mycophenolic acid (MPA), and
      brequinar sodium (BQ) on human IgG4 and IgE synthesis induced by IL-4 or IL-13.
      BQ inhibited IL-4 and IL-13-induced IgG4 and IgE synthesis in cultures of
      peripheral blood mononuclear cells (PBMC) or highly purified B cells costimulated
      by anti-CD40 mAbs in a dose-dependent fashion. CsA and MPA had either suppressive
      or enhancing effects depending on the concentrations tested. Interestingly, BQ
      inhibited IgG4 and IgE synthesis at concentrations of 10(-6)-10(-8) M, which did
      not affect T or B cell proliferation, indicating that the inhibitory effects of
      BQ on Ig production were not directly related to inhibition of T or B cell
      proliferation. In contrast, the inhibitory effects of MPA on Ig production were
      directly associated with inhibitory effects on T and B cell proliferation. CsA
      blocked T and B cell proliferation at the same concentration (10(-7) M) which
      enhanced IgG4 and IgE synthesis, indicating that reduction in T or B cell
      proliferation correlated with enhanced IgE production. CsA also inhibited CD40
      ligand expression and IL-2, IL-4, IL-5, IFN-gamma, and GM-CSF production by
      activated CD4+ T cell clones, whereas MPA and BQ were ineffective, indicating
      that these compounds do not inhibit early events in T cell activation.
      Collectively, our data indicate that BQ, MPA, and CsA block different stages of
      the IgG4 and IgE production process. In addition, we observed that CsA and MPA,
      in contrast to BQ, at lower concentrations can also have potentiating effects on
      the production of these Ig isotypes.

PMID- 7509131
TI  - Calcineurin is a key signaling enzyme in T lymphocyte activation and the target
      of the immunosuppressive drugs cyclosporin A and FK506.

PMID- 7509132
TI  - Efficacy of FK506 in renal transplantation.

PMID- 7509133
TI  - Incidence of CD4+ IL-2R alpha+ and CD4+ CD45RA+ T-cells in progressive multiple
      sclerosis and the influence of short-term (3 months) FK 506 therapy.

PMID- 7509134
TI  - FK 506 inhibits cytokine gene and adhesion molecule expression in psoriatic skin
      lesions.

PMID- 7509135
TI  - Inhibitory effect of FK 506 on autoimmune thyroid disease in the PVG rat.

PMID- 7509136
TI  - Combination of immunosuppressive drugs for organ transplantation.
AB  - Several novel immunosuppressive agents have been developed in recent years. They
      exhibited not only remarkable immunosuppressive potency but also side effects.
      They are still short of the final goal in terms of immunosuppression for organ
      transplantation. Combination treatment is more effective and safer to use, and it
      will prevail in the future.

PMID- 7509139
TI  - New ways of making drugs. RNA and peptides by selection and molecular design.

PMID- 7509137
TI  - Effects of methylprednisolone administration on lymphocyte LECAM-1, CD44, and LFA
      1 expression. Implications for steroid-induced lymphopenia.

PMID- 7509138
TI  - The mechanism of action of FK-506 and cyclosporin A.
AB  - FK-506 and cyclosporin A (CsA) are potent immunosuppressive agents used
      clinically to prevent tissue rejection. Interest in the development of more
      effective immunosuppressive drugs has led to an intense effort toward
      understanding their biochemical mechanism of action with the result that these
      compounds have now become powerful tools used in deciphering the signal
      transduction events in T lymphocyte activation. Although chemically unrelated, FK
      506 and CsA exert nearly identical biological effects in cells by inhibiting the
      same subset of early calcium-associated events involved in lymphokine expression,
      apoptosis, and degranulation. FK-506 binds to a family of intracellular receptors
      termed the FK-506 binding proteins (FKBPs). CsA binds to another family of
      intracellular receptors, the cyclophilins (Cyps), distinct from the FKBPs. The
      similarities between the mechanisms of action of CsA and FK-506 converge upon the
      calcium- and calmodulin-dependent serine-threonine protein phosphatase
      calcineurin (CaN). Both the FKBP/FK-506 complex and the Cyp/CsA complex can bind
      to calcineurin, thereby inhibiting its phosphatase activity. Calcineurin, a
      component of the signal transduction pathway resulting in IL-2 expression,
      catalyzes critical dephosphorylation events required for early lymphokine gene
      transcription.

PMID- 7509140
TI  - Organ-specific autoantigens induce transforming growth factor-beta mRNA
      expression in mononuclear cells in multiple sclerosis and myasthenia gravis.
AB  - Multiple sclerosis (MS) is characterized by patchy accumulations of inflammatory
      cells combined with demyelination. There are mononuclear cells in blood and
      cerebrospinal fluid of patients with MS that produce interferon-gamma and
      interleukin-4 in response to myelin basic protein (MBP) and proteolipid protein
      (PLP). Here we describe autoantigen-induced production of transforming growth
      factor-beta (TGF-beta). This multifunctional cytokine has inhibitory effects on
      the growth, differentiation, and effector functions of activated T cells. Blood
      and cerebrospinal fluid cells were exposed in short-term cultures to MBP and PLP
      and, after hybridization with complementary DNA oligonucleotide probes, they were
      evaluated for TGF-beta mRNA expression. Patients with MS had higher numbers of
      MBP- and PLP-responsive TGF-beta mRNA expressing cells in blood compared with
      control patients with other neurological diseases or myasthenia gravis and a five
      and threefold further increment in their cerebrospinal fluid. In blood of
      patients with myasthenia gravis, where the acetylcholine receptor (AChR) is a
      target for autoaggressive immunity, there were increased levels of AChR
      responsive TGF-beta mRNA expressing cells. Thymectomized myasthenia gravis
      patients showed higher levels of TGF-beta mRNA expressing cells compared with
      patients not thymectomized. Numbers of cells responding to AChR in MS and MBP in
      myasthenia gravis did not differ from numbers found in absence of antigen.
      Patients with other neurological diseases showed infrequent and low responses to
      MBP, PLP, and AChR. Diseases with presumed autoimmune pathogenesis are associated
      with organ-specific autoantigen-induced TGF-beta production, which is increased
      after thymectomy.

PMID- 7509141
TI  - Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to
      bacterial infections in mice.
AB  - Treatment with a single low dose (80 to 800 ng) of interleukin-1 (IL-1) 24 h
      before a lethal bacterial challenge of granulocytopenic and normal mice enhances
      nonspecific resistance. Since IL-1 induces secretion of acute-phase proteins,
      liver proteins which possess several detoxifying effects, we investigated the
      role of these proteins in the IL-1-induced protection. Inhibition of liver
      protein synthesis with D-galactosamine (GALN) completely inhibited the IL-1
      induced synthesis of acute-phase proteins. GALN pretreatment abolished the
      protective effect of IL-1 on survival completely (neutropenic mice infected with
      Pseudomonas aeruginosa) or partially (nonneutropenic mice infected with
      Klebsiella pneumoniae). Pretreatment with IL-6, a cytokine induced by IL-1, did
      not reproduce the protection offered after IL-1 pretreatment, nor did it enhance
      or deteriorate the IL-1-enhanced resistance to infection. A protective effect of
      IL-1 via effects on glucose homeostasis during the acute-phase response was
      investigated by comparing plasma glucose levels in IL-1-treated mice and control
      mice before and during infection. Although glucose levels in IL-1-pretreated mice
      were somewhat higher in the later stages of infection, no significant differences
      from levels in control mice were present, and the glucose levels in control
      treated animals never fell to hypoglycemic values. We conclude that the IL-1
      induced nonspecific resistance is mediated neither by the induction of IL-6 nor
      by the effects of IL-1 on glucose homeostasis. Acute-phase proteins generated
      after IL-1 pretreatment, however, seem to play a critical role in the IL-1
      induced protection to infection.

PMID- 7509142
TI  - Inhibition of visna virus replication by 2',3'-dideoxynucleosides and acyclic
      nucleoside phosphonate analogs.
AB  - A series of acyclic nucleoside phosphonate (ANP) and 2',3'-dideoxynucleoside
      (ddN) derivatives were evaluated for their inhibitory effects on visna virus
      replication and maedi/visna virus-induced syncytium formation in sheep choroid
      plexus cells. Most ANP derivatives inhibited virus replication and syncytium
      formation within a concentration range of 0.2 to 1.8 microM. Among the most
      active ANP derivatives ranked (R)-9-(2-phosphonomethoxypropyl)adenine, (R)-9-(2
      phosphonomethoxypropyl)-2,6-diaminopurine, and (S)-9-(3-fluoro-2
      phosphonomethoxypropyl)adenine. Of the ddN derivatives, 2',3'-dideoxycytidine
      (ddCyd) proved to be the most inhibitory to visna virus-induced syncytium
      formation (50% effective concentration, 0.02 microM). The purine ddN analogs
      (i.e., 2',3'-dideoxyinosine, 2',3'-dideoxyadenosine, 2',3'-dideoxyguanosine, and
      2,6-diaminopurine-2',3'-dideoxyribosine) were 10- to 30-fold less effective, and
      the thymidine derivatives 2',3'-didehydro-2',3'-dideoxythymidine (D4T) and 3'
      azido-2',3'-dideoxythymidine (AZT) were more than 500-fold less inhibitory to
      visna virus than ddCyd. The 5'-triphosphate forms of AZT and D4T were 100- to 600
      fold more inhibitory to visna virus particle-derived reverse transcriptase than
      was the 5'-triphosphate of ddCyd. The apparent discrepancy between the inhibitory
      effects of these ddN derivatives on virus replication and viral reverse
      transcriptase activity most likely reflects differences in the metabolic
      conversion of ddCyd versus D4T and AZT in sheep choroid plexus cells.

PMID- 7509143
TI  - Effect of clindamycin on intracellular replication, protein synthesis, and
      infectivity of Toxoplasma gondii.
AB  - We studied the effects of clindamycin and a combination of clindamycin and
      pyrimethamine on the proliferation of Toxoplasma gondii in cultured mammalian
      cells and the effect of clindamycin on the parasite's RNA and protein syntheses.
      Infected macrophages were treated for 48 h with clindamycin or a combination of
      clindamycin and pyrimethamine, and the 50% inhibitory concentrations for parasite
      growth were 32.50 +/- 1.30 and 10.78 +/- 0.56 micrograms/ml, respectively. A
      modified susceptibility assay was also used to measure the effect of low
      concentrations of clindamycin on T. gondii. Macrophages and bovine turbinate
      cells were infected with low numbers of tachyzoites and were exposed to low
      concentrations of clindamycin for 5 days. In these systems, a concentration of 10
      ng of clindamycin per ml inhibited 50% of the growth of the parasite in
      macrophages, while it completely prohibited the growth of the parasite in
      epithelial cells. When free tachyzoites were preexposed to clindamycin for 4 h,
      the reduction of parasite infectivity was proportional to the amount of drug; 100
      ng of clindamycin per ml reduced the infectivity of T. gondii to 46.5% +/- 8.5%
      of that of the untreated control. A concentration of 40 micrograms of clindamycin
      per ml reduced protein synthesis by 56.2% +/- 6.0% but had no effect on RNA
      synthesis after a 4-h exposure of free tachyzoites of T. gondii to the drug. Our
      results show that long-term exposure to low concentrations of clindamycin reduces
      the level of replication of T. gondii, that clindamycin affects the protein
      synthesis of free parasites, and that clindamycin impairs the ability of
      tachyzoites to infect host cells.

PMID- 7509145
TI  - Correlation of tobramycin-induced inhibition of protein synthesis with
      postantibiotic effect in Escherichia coli.
AB  - Scant data exist on intracellular events during aminoglycoside-induced
      postantibiotic effect (PAE). We examined DNA, RNA, and protein syntheses after
      tobramycin exposure using [3H]thymidine, [14C]uracil, and [14C]alanine
      incorporation in a clinical Escherichia coli strain. Late-log-phase bacteria in
      oxygenated minimal salts medium at 37 degrees C were exposed to tobramycin (7.5
      micrograms/ml) (twice the MIC) for 30 min. Tobramycin caused a kill of 2 log10
      CFU/ml prior to drug removal by filtration and a 5-h PAE, measured by viable
      counts. Excess amounts of labelled precursors were added to tobramycin-exposed
      organisms during, immediately after, and at various intervals following exposure.
      In the presence of tobramycin, DNA, RNA, and protein syntheses were sequentially
      inhibited within 1 generation time. Following drug removal, both DNA and RNA
      syntheses promptly resumed, suggesting readily dissociable nonspecific binding to
      DNA and RNA. However, total protein synthesis did not resume until 4 h later.
      beta-Galactosidase activity, a measure of functional enzymatic protein synthesis,
      was also inhibited for 4 h after drug removal. Bacterium length, measured by
      confocal microscopy, increased during PAE. Two distinct populations eventually
      emerged: one that returned to control dimensions and one that remained
      excessively elongated by the end of PAE (2.5 microns versus 4.0 microns; P <
      0.05). We hypothesize that only viable cells return to the control morphology.
      Flow cytometry showed enhanced DNA complexity during PAE, consistent with either
      impaired cellular protein synthesis in viable cells or perturbations in dying
      cells. In summary, duration of PAE correlated with inhibition of total and
      functional protein synthesis but not DNA or RNA synthesis.

PMID- 7509144
TI  - Viral resistance to the thiazolo-iso-indolinones, a new class of nonnucleoside
      inhibitors of human immunodeficiency virus type 1 reverse transcriptase.
AB  - Thiazolo-iso-indolinone derivatives with high specificity toward the reverse
      transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) were
      identified. The most potent compound, BM +51.0836, inhibited HIV-1 RT at a 50%
      inhibitory concentration of 90 nM in vitro. In cell culture assays, similar 50%
      inhibitory concentrations were obtained with high specificity for HIV-1. These
      substances were equally active against a zidovudine-resistant isolate. No
      antiviral effect was observed with an HIV-2 isolate. HIV-1 isolates resistant to
      the thiazolo-iso-indolinones were generated in cell culture, and the nucleotide
      sequences of the respective RT genes were analyzed subsequently. Comparison of
      the deduced amino acid sequences with the wild-type sequence showed an amino acid
      change at position 181 (Tyr to Cys). Substitutions of amino acid Lys-101 and Lys
      103 as well as Tyr-181 and/or Tyr-188 by site-directed mutagenesis led to
      resistance against the thiazolo-iso-indolinones. A chimeric HIV-2 RT, substituted
      with amino acids at positions 179 to 190 from HIV-1, acquired only partial
      susceptibility to BM +51.0836.

PMID- 7509146
TI  - Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro.
AB  - Recent investigations have shown that some antibiotics also work as
      immunomodulators. We have recently reported that fosfomycin (FOM) has an
      immunomodulatory effect on human B-cell activation. FOM is a unique antibiotic
      which is chemically unrelated to any other known antibacterial agent. In the
      present study, we examined the effect of FOM on human T-cell function. FOM
      inhibited the proliferation of human lymphocytes induced by polyclonal T-cell
      mitogens in a dose-dependent manner. FOM also strongly suppressed mixed
      lymphocyte reaction and interleukin-2 (IL-2) production by T cells. Moreover, FOM
      inhibited the expressions of IL-2 receptor (CD25) and transferrin receptor (CD71)
      on the activated T-cell surfaces. These data suggest that FOM may block the T
      cell division during the transition from G1 to S phase of the cell cycle.
      Combined treatment with FOM and low-dose cyclosporin A or FK506 caused additive
      or synergistic suppression of T-cell proliferation, but not on IL-2 receptor
      expression. It seems that the mode of action of FOM on T-cell function involves a
      specific suppression of IL-2 production.

PMID- 7509147
TI  - Characterization of magnesium efflux from Ehrlich ascites tumor cells.
AB  - Magnesium efflux from intact Ehrlich ascites tumor cells (EATC) has been
      characterized under 0-trans conditions. It is shown that a magnesium-extruding
      mechanism operates in these cells which brings about magnesium efflux up to 20%
      of the cell total content. EATC magnesium efflux is independent from
      extracellular Ca2+ and its apparent velocity is not affected by [Mg2+]o up to 160
      microM. This extrusion, however, is strictly dependent on extracellular Na+ and
      it is inhibited by ouabain (1 mM), amiloride (1 mM), imipramine (0.5 mM) and
      quinidine (1 mM). It is not affected by HMA (5-N,N-hexamethylene) amiloride) (0.5
      microM) and vanadate (0.1 mM). Bumetanide (0.5 mM) enhances magnesium extrusion
      in these cells. EATC magnesium extrusion can be significantly stimulated by db
      cAMP, forskolin, and IBX (3-isobutyl-1-methyl-xanthine). The intracellular
      magnesium distribution, studied also by means of the ionophore A23187, is
      regulated by energy metabolism and cell ATP content. Altogether our data
      demonstrate that EATC exhibit a magnesium extrusion sustained by Na+ gradient
      across the plasma membrane and carried out by a Na+/Mg2+ antiport. In these cells
      magnesium homoeostasis results, regulated efficiently by cell ATP and cAMP
      content.

PMID- 7509148
TI  - Determination of the number of sucrose and acceptor binding sites for Leuconostoc
      mesenteroides B-512FM dextransucrase, and the confirmation of the two-site
      mechanism for dextran synthesis.
AB  - In previous studies on dextransucrase using pulse and chase experiments with
      [14C]sucrose, Robyt et al. [Arch. Biochem. Biophys. 165 (1974) 634-640] proposed
      a two-site insertion mechanism to explain the data for the synthesis of dextran.
      To further establish the validity of the two-site mechanism, the number of
      sucrose binding sites at the active site have been determined by using
      equilibrium dialysis with 6-deoxysucrose, a strong competitive inhibitor for
      dextransucrase. A ligand binding plot gave a straight line that indicated there
      were two sucrose binding sites at the active site. A similar experiment was
      performed using the acceptor, maltose. The ligand binding plot for maltose also
      gave a straight line and indicated that there was one acceptor binding site at
      the active site. These results corroborate the proposed two-site mechanism for
      dextran synthesis. To further test the two-site mechanism, dextransucrase was
      partially inactivated to varying extents by reaction with diethylpyrocarbonate,
      which chemically modifies essential active-site histidines. The various partially
      inactivated enzymes were assayed for dextran synthesis and for the synthesis of
      maltose acceptor products. A plot of the log of the relative percentage of
      dextran synthesized and acceptor products synthesized against varying degrees of
      enzyme inactivation showed that the synthesis of dextran decreased to a greater
      extent than did the decrease of the synthesis of acceptor product. The proposed
      mechanism requires two sucrose sites for the synthesis of dextran and only one
      sucrose site for the synthesis of acceptor product. When one site is modified,
      the synthesis of dextran stops, but the synthesis of acceptor products can
      continue at the other site. Thus, the greater loss of dextran synthesis in
      comparison with the lesser loss of acceptor product synthesis by enzymes modified
      to varying degrees, gives further evidence for the two-site mechanism for dextran
      synthesis.

PMID- 7509149
TI  - [Cancer therapy targeting tumor-induced neovascularization].
AB  - Neovascularization is critical for the growth of tumors and is mediated by
      physiological substances produced by the tumors. Vascular endothelial growth
      factor (VEGF) is one of such potent angiogenic factors. We evaluated VEGF gene
      expression on urinary bladder carcinoma and renal cell carcinoma by Northern blot
      analysis and demonstrated that VEGF was frequently overexpressed in renal cell
      carcinoma, in up to 67% of patients, but not in urinary bladder carcinoma. These
      results suggested that VEGF was produced by renal cell carcinoma and is
      responsible for the hypervascularity of this tumor. TNP-470, an angiogenesis
      inhibitor, is a new type of anticancer drug that inhibits tumor
      neovascularization. We evaluated the antitumor effect of TNP-470 in mice bearing
      B-16 melanoma or Lewis lung carcinoma. TNP-470 at a dose of 20 mg/kg body weight
      inhibited growth of both tumors. The degree of antitumor effect exerted by TNP
      470 was greater than that of ADM (2.5 mg/kg body weight) and as great as that of
      MMC (2.5 mg/kg body weight). Combination of TNP-470 with MMC enhanced the
      antitumor effect. Monitoring of mouse body weight did not reveal any significant
      changes among the treatment groups, indicating that systemic toxicity of TNP-470
      was not severe. These results suggested that TNP-470 was effective for the
      treatment of solid tumor by inhibiting its neovascularization.

PMID- 7509150
TI  - [Control of in vivo characteristics of gene and antisense DNA disposition].
AB  - In order to construct a strategy for control of in vivo disposition
      characteristics of gene and antisense DNA, in vivo stability and basic
      pharmacokinetic properties of DNA were investigated. A model gene, plasmid DNA
      (pCAT), and model oligonucleotide (thymidine 10-mer; T10) derivatives with
      phosphoroamidate substitution at the 3' and/or 5'-terminal internucleotide
      linkage, were rapidly degraded in vivo after intravenous injection into mice. The
      degradation rates were much faster than those observed in in vitro experiments
      using plasma and whole blood, suggesting that they underwent enzymatic
      degradation in other compartments than the blood pool. More than 70% of injected
      pCAT was taken up by the liver within 5 minutes, and the uptake clearance was
      almost identical to the plasma flow rate in the liver. On the other hand, T10
      derivatives were rapidly excreted in the urine and taken up by the kidney and
      liver. The urinary excretion clearance was close to the glomerular filtration
      rate. In an attempt to control T10 disposition characteristics, the
      oligonucleotide was conjugated to a macromolecular carrier, carboxymethyl dextran
      (CMD). The T10-CMD conjugate exhibited increased in vivo stability and prolonged
      plasma circulation time. Thus, the present study has shown that macromolecular
      conjugation is a useful approach to improve in vivo disposition of antisense
      oligonucleotides.

PMID- 7509151
TI  - Effect of alpha thalassaemia trait and enhanced gamma chain production on disease
      severity in beta thalassaemia major and intermedia.
AB  - One hundred and twenty patients with homozygous beta thalassaemia were selected
      to determine the clinical effects of certain genetic factors which may modify
      disease severity. Genetic analysis defined specific beta thalassaemia mutations,
      the alpha thalassaemia genotype, and the presence of an XmnI restriction enzyme
      site, associated with increased fetal haemoglobin (HbF) production under certain
      conditions. Genotypic data with globin chain synthesis were related to the age
      when regular transfusions began and subsequent pubertal development. This study
      showed that the major determinants of disease severity in beta thalassaemia were
      the beta thalassaemia mutations, with co-inheritance of alpha thalassaemia trait
      and coinheritance of a high HbF determinant acting as ameliorating factors. The
      presence of an alpha thalassaemia deletion significantly reduced initial disease
      severity, although the effect on pubertal development was less clear. It is
      concluded that detailed genetic analysis should be performed in all newly
      diagnosed patients with thalassaemia. This, in conjunction with clinical
      assessment, will help to predict disease severity and prognosis.

PMID- 7509153
TI  - Differences in response of patient's blood cells with bronchial asthma to diverse
      house dust mite allergens by histamine release assay.
AB  - A HPLC method was developed for the determination of histamine released from
      washed blood cells of allergic patients after exposure to allergens in the
      presence or absence of plasma. The blood cells used were preserved in a vital
      state at 4 degrees C during at least 6 hours after blood-collecting. The
      responses of blood cells to an appropriately diluted series of a mite feces
      extract (Dff) solution were evaluated in three patient's groups (68 cases of
      hyposensitized, 59 cases of newly visited and 44 cases of the others) with
      bronchial asthma. Washed blood cells from the hyposensitized groups had a
      tendency to release histamine easily even with lower concentration of the Dff
      solution. Both the sensitivities of washed blood cells to Dff or mite body
      extract (Dfb) and the responses of the cells to diverse antigens in neither
      extract differed largely in individual cases. The titer of blocking antibody
      could be expressed as the amount proportional to the concentration of Dff or Dfb.

PMID- 7509152
TI  - Continuous axillary nerve block for chronic pain.
AB  - Continuous axillary nerve block was used to relieve pain after a chemical burn to
      the arm in a child on mechanical ventilation after liver transplantation. The
      analgesia was sufficient to replace parenteral analgesia and allow extubation.

PMID- 7509155
TI  - Treatment for clients with cumulative trauma disorders: using an educational
      model to communicate choices.
AB  - 1. Cumulative trauma disorders comprise more than half of all occupational
      injuries reported in the U.S. 2. Lack of clear definition about cumulative trauma
      disorders causes confusion for clients in the workers' compensation system. 3. A
      teaching poster about cumulative trauma disorders was developed (describing
      prevention, acute care, and rehabilitation) to assist clients in understanding
      this disorder. Emphasis was placed on clients' choice in decision making about
      treatment. 4. Evaluation was carried out using a survey questionnaire. The
      majority of clients thought the poster was "helpful" or "very helpful." Actual
      behavioral change was most noticeable in the categories of "took steps to reduce
      risk factors" and "asked more questions about care."

PMID- 7509154
TI  - [Dermal reactions in children with atopic dermatitis--changes in
      histamine/tryptase levels in skin chambers. Report 1].
AB  - In the present study, we used the skin chamber method to determine histamine and
      tryptase released by continuous loading of a single antigen on the skin in order
      to evaluate dermal reactions produced and thereby obtain greater insight into the
      role of type I allergic reactions in children with atopic dermatitis. The
      subjects were 46 children, 23 males and 23 females aged 10.6 +/- 4.3 years on the
      average, who were being treated at the National Children's Hospital for moderate
      or severer atopic dermatitis. Mite antigen stimulation was carried out by the
      skin chamber method upon admission and histamine and tryptase levels in collected
      antigen solution were determined. Histamine levels in the chamber were increased
      significantly at 6, 12 and 24 hrs after stimulation compared to the control
      levels (p < 0.01). Tryptase levels were increased 2 hrs after stimulation but
      decreased with time thereafter. Histamine and tryptase levels were significantly
      correlated 2 hrs after stimulation, with a correlation coefficient of 0.954 (p <
      0.01). No significant correlation was observed 24 hrs after stimulation. These
      findings indicate that children with severe atopic dermatitis have great skin
      reactivity and very sensitive to stimulation by antigens. Mast cells and
      basophils are thought to be involved in immediate and delayed type reactions,
      respectively.

PMID- 7509156
TI  - [Preoperative shaving: is it still necessary? A new nursing guideline.
      Verpleegkundig Wetenschappelijke Raad].

PMID- 7509157
TI  - Effects of acute and chronic lithium treatment on amphetamine-induced dopamine
      increase in the nucleus accumbens and prefrontal cortex in rats as studied by
      microdialysis.
AB  - The effects of acute and chronic administration of lithium (Li) on the basal
      levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid
      (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA), and the amphetamine-induced DA
      increase were assessed in the Nucleus Accumbens (NAC) and Prefrontal Cortex (PFC)
      by brain dialysis in freely-moving rats. Acute Li (2 meq/L) was locally
      administered by reverse dialysis. Chronic Li (2 meq/kg) was intragastrically
      administered for 14 days. No effect was observed after acute Li administration.
      However, after chronic Li administration, the basal levels of DOPAC and the
      amphetamine-induced DA increase in the NAC were significantly higher in the Li
      treated rats than in the saline-treated controls. In the PFC, while the
      amphetamine-induced DA increase was not affected by chronic Li, the basal levels
      of DA and DOPAC were significantly decreased after Li administration. The effects
      of chronic Li in the NAC could be due to increased synthesis and/or decreased
      release of DA, whereas in the PFC the effects could be due to a decreased
      synthesis of DA. The absence of effects of acute Li administration is in
      agreement with the therapeutic inefficacy of the acute use of the cation. The
      changes observed after chronic treatment in the NAC and the PFC could be related
      to the effects of Li on mood disorders and cognitive functions, respectively.

PMID- 7509158
TI  - Naturally-occurring isoquinolines perturb monamine metabolism in the brain:
      studied by in vivo microdialysis.
AB  - Naturally occurring isoquinolines affected the monoamine metabolism in the rat
      striatum, as proved by in vivo microdialysis technique. By analysis of monoamines
      and their metabolites in the dialysate, dopamine-derived 6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinolines were found to inhibit monoamine oxidase and catechol-O
      methyltransferase activity. 1-Methyl- and 2-methyl-6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline were found to inhibit activity of type A monoamine oxidase
      most markedly. To compare the structure-activity relationship, corresponding
      isoquinolines without a catechol structure were also examined. The inhibition by
      catechol isoquinolines was more manifest than those without a catechol structure.
      Among latter isoquinolines, N-methyl-isoquinolinium ion was the most potent
      inhibitor of monoamine oxidase. In addition, catechol isoquinolines increased
      monoamine levels in the brain. The number and the site of the methyl group are
      essentially required for the inhibition of monoamine oxidase and a catechol
      structure for that of catechol-O-methyl-transferase. These results are discussed
      in relation to possible involvement of these isoquinolines to the clinical
      features of some neuro-psychiatric diseases, such as alcoholism or in L-DOPA
      therapy.

PMID- 7509159
TI  - Serum antibodies to viral pathogens and Toxoplasma gondii in HIV-infected
      individuals.
AB  - Sera from 38 HIV-infected individuals were examined longitudinally for antibodies
      to viruses that may increase morbidity in HIV infection, as well as commensal
      viruses and Toxoplasma gondii. HTLV infection was seen in Norway for the first
      time as four patients had antibodies to HTLV-II and one had antibodies to HTLV-I.
      Antibodies to hepatitis B virus (HBV) were found in 47.2%, while 21.6% of the
      patients had antibodies to hepatitis C virus (HCV). There was no evidence of
      acquisition of HBV or HVC during the mean observation period of 2 years. A titre
      increase in CMV antibody with time was observed for 7 out of 21 patients and a
      decrease for 2 patients. For Epstein-Barr virus, herpes simplex, varicella
      zoster, rubella and measles viruses, human polyomavirus BK as well as for
      Toxoplasma gondii, antibody prevalences and titres were within the range seen in
      normal populations. Also, no longitudinal changes were observed in titres of
      these antibodies, indicating that humoral immunity remained intact during the
      study period. The high prevalences of HTLV-I/II, HBV and HCV antibodies in HIV
      infected patients reflect common modes of virus transmission, and the
      fluctuations in CMV antibody titre are indicative of reactivations. Such
      coinfections may influence disease progression.

PMID- 7509160
TI  - Glial cells of the oligodendrocyte lineage express both kainate- and AMPA
      preferring subtypes of glutamate receptor.
AB  - mRNAs for AMPA- and kainate-preferring glutamate receptor subunits are expressed
      abundantly in the CNS, yet functional studies of neurons and glia from brain
      suggest selective expression of AMPA receptors. We now show that glial cells of
      the O-2A lineage express rapidly desensitizing responses to kainate, mRNAs for
      GluR6, GluR7, KA-1, and KA-2, rapidly desensitizing responses to AMPA, and mRNAs
      for GluR-B, -C, and -D. Analysis of glutamate receptor currents in single cells
      reveals two receptor populations with high and low affinity for kainate and
      different sensitivity for potentiation by concanavalin A and for block of
      desensitization by cyclothiazide. Our experiments describe the characterization
      of native kainate-preferring receptors in glia and reveal coexpression in single
      cells of functional AMPA- and kainate-preferring receptors.

PMID- 7509162
TI  - Inhibition of lymphokine-activated killer cells by human pulmonary macrophages:
      discordance between up-regulation of the beta chain (p75) of the interleukin-2
      receptor on CD56+ cells and limited response to interleukin-2.
AB  - Previous studies have demonstrated that interaction of interleukin-2 (IL-2) with
      the beta chain (p75) of the IL-2 receptor on CD56+ cells is necessary for the
      development of lymphokine-activated killer (LAK) activity and proliferation of
      CD56+ LAK cells in response to IL-2. Human pulmonary macrophages (PM) are potent
      inhibitors of LAK cells in vitro, and purified resident human lung lymphocytes
      show limited LAK activity in response to IL-2, suggesting that IL-2-p75
      interactions may be altered locally in vivo. In the current study, human PM or
      anti-p75 inhibited LAK activity and proliferation of CD56+ cells in response to
      IL-2. This effect was produced by either live or paraformaldehyde-fixed PM, but
      not peripheral blood monocytes, suggesting that a membrane signal on PM was
      responsible for inhibition. Suppression of LAK function and proliferation in
      response to IL-2 occurred despite a rapid up-regulation of p75 on CD56+ cells
      after 24 h of incubation with PM. Greater than 70% of CD56+ cells expressed p75
      after culture with either live or fixed PM, compared with 10 to 15% at 0 h or
      after 24 h of incubation in IL-2 alone. p75 dim and p75 bright cells increased
      equally, suggesting that p75 was being up-regulated on previously p75- cells
      rather than an overexpansion of one subset of p75+ cells. The increase in p75
      expression in the presence of PM paralleled with an increase in IL-2 binding to
      these lymphocytes. These results suggest that PM inhibit the activation of LAK
      cells at a point distal to IL-2-p75 binding.

PMID- 7509163
TI  - Control of keratin gene expression by vitamin A in tracheobronchial epithelial
      cells.
AB  - Vitamin A (retinol) treatment induces (and/or enhances) mucous cell
      differentiation and alters keratin gene expression in cultured airway epithelial
      cells of human and nonhuman primate origin. We observed that retinol greatly
      reduced the synthesis of keratins 5, 6, 14, 16, and 17, but slightly enhanced
      keratins 7, 8, 10, 13, 15, 18, and 19. These changes were also reflected at the
      mRNA level as demonstrated by cell-free translation and by cDNA cloning of human
      keratin genes based on differential hybridization. One of these cDNA clones,
      HT27, isolated from the cDNA library of human tracheobronchial epithelial cells
      and whose expression in cultured cells was greatly suppressed by retinol, had a
      nucleotide sequence identical to the C-terminus of keratin 16. The identity of
      this clone was further confirmed by Western blot analysis using an antibody
      specific to the 15-amino acid synthetic peptide and the C-terminal sequence.
      Using this cDNA clone and two known keratin clones, pKA1 (keratins 5 and 6) and
      pKB2 (keratin 14), we found the levels of these corresponding mRNAs in cultured
      cells to be reduced 10- to 25-fold after treatment of cells with vitamin A. The
      inhibition was time- and dose-dependent with respect to retinol and was sensitive
      to prior treatment with cycloheximide. However, nuclear run-on transcriptional
      assays revealed no significant reduction of the synthesis of these messages in
      retinol-treated cultures. Furthermore, no change in the half-life of these mRNAs
      was observed in cells after the retinol treatment. Based on these results, we
      conclude that vitamin A indirectly controls the synthesis of these keratins at
      the post-transcriptional level.

PMID- 7509161
TI  - Subunit composition at the single-cell level explains functional properties of a
      glutamate-gated channel.
AB  - The diversity of known glutamate-gated channels has been markedly increased by
      the discovery of multiple subunits and their spliced and edited variants. These
      subunits can potentially form different oligomeric complexes with diverging
      properties. A crucial question is therefore to determine the actual subunit
      composition of naturally occurring glutamate receptors. We have coupled patch
      clamp recordings and reverse transcription followed by PCR amplification to
      correlate the presence of mRNAs for each subunit and the functional properties of
      native glutamate receptors at the single-cell level. In a homogeneous population
      of functionally identified hippocampal neurons (type II) in culture bearing a
      glutamate receptor of the AMPA subtype with a high calcium permeability, we found
      that, among the multiple subunits, only two, the flop forms of GluR1 and GluR4,
      were expressed. In particular, GluR2 was never detected. This composition
      explains the uncommon properties of AMPA receptors in type II neurons.

PMID- 7509165
TI  - Clonogenic potential of myeloid leukaemia cells in vitro is restricted to
      leukaemia cells expressing the CD34 antigen.
AB  - Cells from patients with acute myeloid leukaemia (AML) or chronic myeloid
      leukaemia (CML) were separated into CD34-enriched and CD34-depleted
      subpopulations. The clonogenic capacities of these two subpopulations were then
      compared to each other and to the original unseparated cell population. In every
      study, the CD34-enriched subpopulation demonstrated a substantial increase in
      clonogenicity in vitro in comparison with the original cell population, while the
      reverse was the case for the CD34-depleted subpopulations. For reasons not clear
      at present, the enrichment for clonogenic cells far exceeded the enrichment for
      cells expressing the CD34 antigen. Additionally, the clonogenic potential was
      found to be unrelated to the level of myc expression in the various cell
      populations.

PMID- 7509164
TI  - Expression of surfactant proteins in embryonic rat lung.
AB  - Because surfactant proteins A, B, and C (SP-A, SP-B, and SP-C) are putative
      markers for alveolar epithelial type II cells, we investigated their expression
      in embryonic rat lung (12 to 15 days, term = 22 days). The expression of the
      messages for SP-A, SP-B, and SP-C was assessed by the reverse-transcriptase
      polymerase chain reaction (RT-PCR). Embryonic rat lung at 12 days' gestation
      lacked detectable mRNAs for all three surfactant proteins. Messages for SP-A, SP
      B, and SP-C were, however, present in embryonic rat lung at 13 days' gestation.
      Expression of SP-A mRNA increased in embryonic rat lung with advancing gestation.
      Surfactant protein mRNA expression during the embryonic period of lung
      development was limited to the epithelial cells. The expression of SP-A mRNA,
      while limited to the lung, did not appear to be a marker for cells destined to
      become type II cells, since it was detected in the trachea and the presumptive
      main bronchial ducts of embryonic rat lung at 13 days' gestation, as well as in
      the distal lung prealveolar region. Expression of both SP-B and SP-C mRNAs in
      embryonic lung was confined to the distal portion of the ductal system, although
      message of SP-C was also found in brain and kidney. These results suggest that
      none of the three surfactant protein mRNAs studied are, at this early stage of
      lung development, specific for cells destined to become type II pneumocytes.

PMID- 7509166
TI  - Response to increasing doses of octreotide in a patient with carcinoid syndrome.

PMID- 7509168
TI  - Mercury concentrations in hair exposed in vitro to mercury vapor.
AB  - Hair is often used as an index of environmental and industrial exposure to
      different metals. The interpretation of metal levels in hair is difficult because
      of the risk of external contamination. The aim of this study was to define the
      degree of external contamination of hair exposed in vitro to mercury vapor.
      Specimens of hair were exposed to concentration: 0.026, 0.21, and 2.7 mg Hg/m3
      for 2-28 d. Mercury levels in hair increased during 28 d of exposure 2, 3 and 13,
      times, respectively, when compared to initial values. Mercury levels in hair
      exposed to the first and second (but not third) concentration of mercury vapor
      attained a steady state on the 21st d of exposure. The contamination of hair with
      mercury could not be removed by washing with water, solvent, and detergent. Hair
      may be used as an index of internal uptake of mercury provided that it was not
      externally exposed to mercury vapor. In cases of occupational exposure to mercury
      vapor, hair could become a useful tool for monitoring exposures.

PMID- 7509169
TI  - Trace elements in hair of Blackfoot disease.
AB  - Blackfoot disease is a peripheral vascular disease resulting in gangrene of the
      lower extremities. Though extensive epidemiological study has implicated that
      high arsenic content in artesian well water of the endemic area bears some
      important connection with the disease, the etiology of the disease is still
      unknown. In this study, attention is paid to multielement determination in order
      to find out whether the trace elements in hair of Blackfoot disease patients are
      different from those of the controls. Experimental results indicate that the
      concentrations of As and Se in hair of patients are significantly higher than
      those of the controls, but Ca and Zn are significantly lower than those of the
      controls. The possible connection of these elements with the etiology of the
      disease is discussed.

PMID- 7509170
TI  - Effect of age and sex on copper-induced toxicity in the macular mutant mouse. An
      animal model for Menkes' kinky-hair disease.
AB  - It was determined if the sensitivity in macular mutant mouse to copper-induced
      toxicity was affected by sex or age. The sensitivity in 6-8-d-old or 3-4-wk-old
      macular mutant mouse to copper-induced toxicity was not affected by sex. However,
      8-9-wk-old mutant females were more sensitive to copper-induced toxicity than
      mutant males. Furthermore, 6-8-d-old or 3-4-wk-old mutant males were more
      sensitive to copper-induced toxicity than 8-9-wk-old mutant males. However, age
      related differences in sensitivity to copper-induced toxicity did not occur
      significantly in mutant females. On the other hand, in the case of normal mice,
      the sensitivity in 6-8-d-old or 3-4-wk-old mice to copper-induced toxicity was
      not also affected by sex. In contrast to mutant, however, 8-9-wk-old normal males
      were more sensitive to copper-induced toxicity than 8-9-wk-old normal females.
      Adult males were also more sensitive to copper-induced toxicity than 6-8-d-old or
      3-4-wk-old males. However, age-related differences in sensitivity to copper
      induced toxicity did not occur significantly in normal females. These results
      indicate that sex- and age-related differences in the copper-induced toxicity
      exist in macular mutant mice.

PMID- 7509167
TI  - The use of reverse transcriptase-polymerase chain reaction (RT-PCR) to
      investigate specific gene expression in multidrug-resistant cells.
AB  - Expression of specific genes at the level of mRNA can be studied using techniques
      such as Northern blot, slot/dot blot, RNase protection assay, in situ
      hybridisation and RT-PCR. In this article these methods of analysis are compared;
      RT-PCR offers higher levels of specificity and sensitivity than traditional
      methods of RNA analysis and as such has become the method of choice for the study
      of gene expression. The RT-PCR technique is described in detail with sections
      dealing with RNA extraction, choice of primers (including the use of cDNA
      sequence data bases), PCR and RT-PCR protocols in addition to the limitations of
      the method. The study of one particular mRNA transcript (MDR1) using RT-PCR is
      discussed in detail. Recently described methods for quantitation of PCR products
      are discussed. Quantitative PCR would appear to offer a method of studying gene
      expression in a more extensive way than has been possible to date.

PMID- 7509171
TI  - Effect of cell density on the inhibition of tumor cell attachment and nucleic
      acid synthesis by selenite.
AB  - The effect of cell density on the sensitivity of tumor cells to selenite has been
      examined. The inhibitory effect of selenite on cellular DNA and RNA synthesis was
      significantly greater in higher density cultures of HeLa cells and A2780 ovarian
      tumor cells. High-density cells were also more sensitive to the inhibitory effect
      of selenite on cell attachment. This difference could not be accounted for by a
      higher intracellular level of glutathione, since there was no significant
      difference between the cells at high or low density. The high-density cells were
      found to take up more selenium per cell during the exposure period; the resulting
      higher level of intracellular Se could explain their greater sensitivity to
      selenite. This hypothesis is supported by the observation that DNA synthesis in
      nuclei isolated from high-density cells did not exhibit higher sensitivity to
      inhibition by selenite than synthesis in nuclei isolated from low-density cells.

PMID- 7509173
TI  - The selenium content of selected meats, seafoods, and vegetables from Lubbock,
      Texas.
AB  - The selenium content of some frequently consumed foods from a commercial beef
      packer, a road-side vendor, and local stores in Lubbock, Texas was determined and
      compared to selenium data for the same or similar foods in the United States and
      from other countries. The comparative content of selenium in foods covered the
      period of time between 1970 and 1993. Our selenium analyses of foods show that on
      a fresh weight basis, the selenium content of seafoods > commercial beef > pork >
      ground beef > chicken. Cooking, air- or freeze-drying increased the selenium
      content of all foods significantly. When the selenium content of local foods is
      compared to similar foods in the United States and other countries, with few
      exceptions, there exists great uniformity in the selenium content in the major
      food groups, meats, fish, milk, and vegetables. New Zealand, known for its low
      soil selenium, had the lowest comparative food selenium content.

PMID- 7509174
TI  - Type II diabetes mellitus, congestive heart failure, and zinc metabolism.
AB  - Zinc status was assessed in patients with type II diabetes mellitus and
      congestive heart failure (CHF). Three groups of patients were enrolled into the
      study: Group 1: 15 patients with type II diabetes mellitus and CHF; Group 2: 20
      patients with isolated type II diabetes mellitus; and Group 3: nine patients with
      isolated CHF. Twenty-four-hour urine was measured for creatinine, protein, and
      zinc, and blood was drawn for creatinine, proteins, liver enzymes, hemoglobin
      A1c, and zinc. Insulin treatment and hemoglobin A1c were comparable in the
      diabetic patients of groups 1 and 2, but group 1 was also treated with captopril
      and diuretics like the CHF patients of group 3. Plasma zinc levels were
      statistically similar in all three groups, but urinary zinc excretion (mumol/24
      h) and urinary zinc: creatinine (mumol/mmol) ratio were significantly higher in
      the type II diabetics and CHF group (27.2 +/- 1.5; 1.69 +/- 0.6, respectively)
      compared to the diabetic patients alone (19.4 +/- 0.76; 0.97 +/- 0.3,
      respectively) and the CHF patients (9.7 +/- 0.3; 0.62 +/- 0.3, respectively). and
      the CHF patients (9.7 +/- 0.3; 0.62 +/- 0.3, respectively). Patients with type II
      diabetes mellitus and CHF were treated with higher doses of captopril than the
      CHF patients (56.25 +/- 24 mg vs 18.8 +/- 11 mg P < 0.05). Thus, patients with
      type II diabetes mellitus and CHF excrete larger amounts of zinc, which may
      eventually lead to zinc deficiency.

PMID- 7509172
TI  - Reversal of selenium and zinc deficiencies in chronic hemodialysis patients by
      intravenous sodium selenite and zinc gluconate supplementation. Time-course of
      glutathione peroxidase repletion and lipid peroxidation decrease.
AB  - In six chronic dialyzed uremic patients, an intravenous sodium selenite (Se 50
      micrograms during 5 wk and then 100 micrograms) and zinc gluconate (Zn 5 mg)
      supplementation was performed during 20 wk at each dialysis session three times
      weekly. Before supplementation, plasma Se and Zn, plasma and erythrocytes (RBC)
      antioxidant metallo-enzymes glutathione peroxidase (GPX), and superoxide
      dismutase (SOD) were significantly decreased, whereas lipid peroxidation (as
      thiobarbituric acid reactants TBARs) was increased. To obtain a significative
      change in plasma selenium, we had to use an Se dose of 100 micrograms/dialysis
      session. Then, treatment-increased plasma Se (from 0.58 +/- 0.09 to 0.89 +/- 0.16
      mumol/L) led to a repletion of RBC-GPX (from 29.6 +/- 6 to 43 +/- 5.8 U/g Hb) and
      increased plasma GPX levels (from 62 +/- 13 to 151 +/- 43 U/L). Plasma Zn and RBC
      SOD did not vary significantly. The change of TBARs was not observed between wk 1
      and 4. They decreased significantly between wk 4 (4.80 +/- 0.21 mumol/L) and wk
      20 (4.16 +/- 0.26 mumol/L). We noted a low correlation between TBARs and plasma
      GPX. A strong correlation was observed between Se and plasma GPX. The reversal of
      Se deficiencies should reduce oxidative damage observed in these patients.

PMID- 7509175
TI  - Selenium status in Charadriiformes. Tissue distribution and seasonal,
      geographical, and species variation.
AB  - The distribution of selenium in a marine wader, the Oystercatcher (Haematopus
      ostralegus) is given by the levels in 15 tissues and plasma. Red blood cells
      (RBC) contain the highest level (23 mg/kg dry wt) followed by liver, lung, and
      kidney (17-19 mg/kg). Most other tissues range from 3-10 mg/kg. The average
      kidney and liver concentrations of the Oystercatcher belong to the concentrations
      characteristic in birds. However, the Oystercatcher's tissue selenium
      concentrations are in general four- to fivefold mammalian levels, but in liver
      and lung, 11- to 13-fold and in the RBC, 12- to 33-fold. The selenium plasma and
      RBC levels of the Oystercatcher vary during the year from 280 to 410 micrograms/L
      and 13 to 30 mg/kg dry wt, respectively; the plasma concentrations are positively
      correlated with the RBC selenium concentrations. An overview of literature data
      shows that the selenium kidney and liver concentrations of birds do not vary with
      geographical latitude and size (length) of the birds. In species of the orders
      Charadriiformes and Procellariiformes, high selenium kidney, and to a lesser
      extent liver, concentrations may occur. A function of selenium in antioxidation
      is suggested.

PMID- 7509176
TI  - The bioavailability of various selenium compounds to a marine wading bird.
AB  - The uptake of dietary selenium (about 3.5 mg/kg AF dry wt) as selenomethionine,
      selenocystine, selenite, selenate, and fish selenium in the plasma and red blood
      cells (RBC) of the oystercatcher has been investigated. The birds received the
      various selenium compounds subsequently, for at least 9 wk. After dietary
      supplementation of selenocystine, selenite, and selenate, plasma selenium was
      about 350 micrograms/L and RBC selenium 2.1 mg/kg dry wt. After supplementation
      of selenomethionine, the plasma concentration increased to 630 micrograms/L, and
      the RBC concentration to 4.1 mg/kg dry wt. When the fodder contained 3.1 mg/kg
      fish Se, an average plasma and RBC concentration of 415 micrograms/L and 14.4
      mg/kg dry wt, respectively, was measured. The maximal increase of the selenium
      concentration in the plasma was attained at first sampling, 14 d after a change
      in dietary selenium (selenomethionine or fish Se); the uptake seemed to be a
      concentration-regulated process. RBC concentrations (Y in mg/kg drug wt)
      increased with time (X in d) according to Y = a - b e-cX. Fifty percent of the
      total increase was attained within 17 d, suggesting that diffusion into the RBC
      played a role. The selenium concentration in the plasma was positively correlated
      with the (fish)Se concentration in the fodder; the RBC concentration (60 d after
      the change in diet) was positively correlated with the plasma concentration. When
      the diet contained fish Se, the blood selenium concentrations of the captive
      birds were similar to the concentrations measured in field birds. Fish Se is a
      yet undetermined selenium compound. The present experiment showed that fish Se
      differed from selenomethionine, selenocystine, selenite, or selenate in uptake
      from the food and uptake in the RBC.

PMID- 7509177
TI  - Increased plasma pyridoxal-5'-phosphate when alkaline phosphatase activity is
      reduced in moderately zinc-deficient rats.
AB  - It is generally believed that the zinc metalloenzyme alkaline phosphatase is
      required to hydrolyze phosphorylated forms of vitamin B-6 prior to their use. To
      test this hypothesis, rats were fed a liquid diet containing either adequate or
      moderately low zinc during gestation and lactation. Zinc deficiency was produced
      in dams evidenced by significant reductions in zinc concentration of plasma
      (49%), liver (25%), and femur (24%), and plasma alkaline phosphatase activity
      (48%). Plasma pyridoxal-5'-phosphate (PLP), which significantly increased (61%)
      in these same rats, was negatively correlated (r = -0.74, P < 0.02) with plasma
      alkaline phosphatase activity. Maternal liver PLP concentration was unaffected by
      zinc status. The zinc and vitamin B-6 relationship seen in dams was less
      observable in offspring. Stimulation of erythrocyte alanine aminotransferase
      activity by exogenously added PLP in vitro tended to be higher in both moderately
      zinc-deficient mothers and their offspring, but the difference was not
      significant. Our results support the hypothesis that alkaline phosphatase
      activity is required for the hydrolysis of plasma PLP. Our results also suggest
      that zinc status as alkaline phosphatase activity should be defined in an
      individual if plasma PLP is to be used as an indicator of vitamin B-6 status.

PMID- 7509178
TI  - Element variations in pregnant and nonpregnant female rats orally intoxicated by
      aluminum lactate.
AB  - Pregnant or nonpregnant female rats were orally intoxicated by aluminum lactate
      (400 mg Al/kg/d) from d 0-19 of gestation to determine the treatment's influence
      on element variations in the females and their fetuses. The aluminum levels of
      plasma, liver, spleen, and kidneys were significantly higher in treated pregnant
      rats than non-pregnant female rats. Differences of P, Ca, Cu, Zn, or Mg levels
      were observed among the four groups of female rats in the tissues and plasma. The
      aluminum content of the 20-d-old fetuses did not significantly differ between the
      treated and control groups. On the contrary, calcium and magnesium levels in the
      whole fetuses from treated or nontreated dams are significantly different.

PMID- 7509179
TI  - Effects of calcium and sugars on intestinal manganese absorption.
AB  - An in vivo luminal perfusion technique was used to investigate the influence of
      Ca, Mg, lactose, and glucose on Mn absorption in different segments of the rat
      intestine. Mn absorption was determined by measuring disappearance of 54Mn
      activity from the perfusion solution containing 0.1 or 0.01 mmol/L Mn. Na and
      water absorption were also determined. Mn absorption decreased during the first
      30 min of perfusion to reach a steady state thereafter. Ca (1 mmol/L) inhibited
      Mn absorption in the proximal jejunum and in the colon, whereas Mn absorption was
      increased by Ca in the distal jejunum. Mg (1 mmol/L), lactose, and glucose (25
      mmol/L each) had no effect on Mn absorption in the jejunum. These results can be
      explained by a direct interaction of Mn and Ca during transcellular Ca transport
      in the proximal jejunum and colon. The reason for the stimulatory effect of Ca in
      the distal jejunum is unknown.

PMID- 7509180
TI  - Glucocorticoid and polyamine involvement in zinc uptake by COMMA-1D mammary
      epithelial cells.
AB  - The objective was to determine if a mammary cell line shows glucocorticoid
      stimulation of Zn uptake, and to determine whether polyamines mediate this
      stimulation. 65Zn uptake by COMMA-1D mouse mammary epithelial cells over a 24-h
      period increased significantly in cells administered 10(-7) or 10(-6) M
      hydrocortisone. Incorporation of 65Zn over a 1-h period was not hydrocortisone
      responsive, suggesting that these incubation times represent uptake into
      different pools. The rate of entry into the cells over a 15-min period was
      significantly increased by supplementing cells with hydrocortisone with or
      without prolactin. Initially, cells grown in lactogenic hormone-supplemented
      media (10(-6) M hydrocortisone + 5 micrograms/mL ovine prolactin) had up to 65%
      greater 65Zn uptake over 24 h than cells in nonsupplemented growth media. 65Zn
      uptake from hormone media with the spermidine synthesis inhibitor methylglyoxal
      bis-(guanylhydrazone) (MGBG, 10(-5)M) added was less than from growth media.
      Exogenous spermidine (10(-6)-10(-3)M) added to the MGBG + hormone media increased
      65Zn uptake. Difluoromethylornithine (DFMO), an inhibitor of spermidine synthesis
      that blocks ornithine decarboxylase, caused a slight dose-dependent decrease in
      65Zn uptake over the range 10(-6)-5 x 10(-3)M (p < 0.002) and tended to decrease
      65Zn-uptake in lactogenic hormone-stimulated cells with 8 h of incubation, but
      not at other times. These data show that Zn uptake in mammary epithelial cells
      can be hormonally mediated by glucocorticoids and suggest that polyamines may be
      intracellular mediators of this effect.

PMID- 7509181
TI  - Effect of molybdenum supplementation on N-nitroso-N-methylurea-induced mammary
      carcinogenesis and molybdenum excretion in rats.
AB  - Molybdenum (Mo) supplementation reduces the incidence of nitrosamine-induced
      tumors in the esophagus and forestomach of laboratory animals, and the incidence
      of mammary cancer in female rats induced by N-nitroso-N-methylurea (NMU). The
      present study was conducted to evaluate the effect of graded amounts of Mo on NMU
      induced mammary carcinogenesis, and on the excretion of Mo and copper (Cu).
      Female Sprague-Dawley rats aged 5 wk were given ad libitum a low-Mo (0.026 mg/kg)
      diet and deionized water. After 15 d, a single SC injection of 50 mg NMU/kg body
      wt was administered to each of 30 rats in groups 2-5. Eight rats in group 1
      served as untreated control. One week after the carcinogen treatment, 0.1, 1.0,
      or 10 mg Mo from sodium molybdate were added to each liter of drinking water for
      groups 3, 4, and 5, respectively. Groups 1 and 2 did not receive any Mo
      supplementation. After the rats had been Mo-supplemented for 38, 67, and 85 d, 48
      h urine and fecal samples were collected from the same 48 rats, and Mo and Cu
      were determined. Molybdenum seemed to have little effect on Cu excretion. At each
      time interval, animals fed 0 or 0.1 mg Mo/L excreted more Mo in feces than in
      urine, whereas rats fed 1 and 10 mg Mo/L water excreted more Mo in urine than in
      feces, which indicates that Mo absorption was not easily saturated as the amount
      of Mo increased. However, the liver became saturated with Mo when 0.1-1 mg Mo/L
      was fed. The total number of palpable tumors per group 101 d after NMU
      administration was 109, 115, 101, and 81, and the total carcinomas per group were
      92, 96, 86, and 65 for the animals in groups 2-5, respectively. The results
      indicate that supplemental Mo in the amount of 10 mg/L of drinking water
      inhibited mammary carcinogenesis.

PMID- 7509182
TI  - PREDITOP: a program for antigenicity prediction.
AB  - A program (PREDITOP) for predicting the location of antigenic regions (or
      epitopes) on proteins is described. This program and the associated ones are
      written in Turbo Pascal and run on IBM-PC compatibles. The program contains 22
      normalized scales, corresponding to hydrophilicity, accessibility, flexibility,
      or secondary structure propensities. New scales are easily implemented. An
      hydrophobic moment procedure has also been implemented in order to determine
      amphiphilic helices. The program generates a result file where the values
      represent a particular physicochemical aspect of the studied protein. PREDITOP
      can display one or several result files by simple graphical super-imposition.
      Curve combinations can be done by the ADDITIO or MULTIPLI routines which create a
      new result file by adding or multiplying previously calculated files representing
      several propensities. The program is useful and efficient for identifying
      potential antigenic regions in a protein with the aim of raising antibodies
      against synthesized peptides which cross-react with the native protein.

PMID- 7509183
TI  - The prospects for new treatments in age-related macular degeneration.

PMID- 7509184
TI  - Treatment of choroidal neovascularisation in age-related macular degeneration
      with interferon alfa-2a and alfa-2b.
AB  - Forty eight eyes of 42 patients with choroidal neovascular membranes and age
      related macular degeneration who received three different dose regimens of
      systemic interferon alfa-2 were studied retrospectively. The response to
      treatment of 41 eyes of the 37 patients who received at least 4 weeks' treatment
      was analysed with respect to the change in size of the choroidal neovascular
      membrane and the visual acuity compared with pretreatment levels. The size of the
      membrane at the end of the course of treatment had decreased in seven (17%) eyes
      overall, not changed in 16 (39%), and increased in 18 (44%). At the end of
      treatment, the visual acuity had improved in seven (17%) eyes, not changed in 27
      (66%), and deteriorated in seven (17%). With an average follow up of 10 months
      after treatment, the visual acuity had deteriorated compared with the
      pretreatment value in 21 out of 41 (51%) eyes. Vision improved in some fellow
      eyes with disciform scars. Side effects were common and often severe. The data
      suggest that one of the major effects of interferon alfa may be to decrease
      vascular permeability. While further research may identify a place for interferon
      alfa in the treatment of choroidal neovascularisation, we were unable to
      demonstrate that the treatment regimens of systemic interferon alfa we used
      caused a dramatic benefit to patients with exudative age-related macular
      degeneration.

PMID- 7509185
TI  - Clinical experience with interferon alfa-2a for exudative age-related macular
      degeneration.
AB  - There has been recent interest in the use of systemic interferon alfa-2a
      treatment for choroidal neovascular membranes (CNV). Here a pilot study is
      reported in which 10 patients with exudative age-related macular degeneration
      (ARMD) have been treated with a course of interferon injections. Of nine eyes
      with CNV there has been clinical and angiographic improvement in one eye and
      maintenance of visual acuity at pretreatment levels in three eyes (mean follow up
      period 7.6 months). Clinical appearance in five eyes was unchanged but these eyes
      still had active CNV. Two eyes with pigment epithelial detachment showed no
      clinical or angiographic change after interferon therapy although visual acuity
      in one eye had improved. Interferon alfa-2a may have a role to play in the
      treatment of ARMD as an adjunct to laser photocoagulation.

PMID- 7509186
TI  - Gillespie syndrome reported as bilateral congenital mydriasis.

PMID- 7509187
TI  - Serpiginous choroiditis: an unusual presentation of ocular sarcoidosis.

PMID- 7509188
TI  - Decreasing CD4/CD8 ratio during prolonged four-drug chemotherapy plus interferon
      treatment for metastatic melanoma.
AB  - A chemotherapy regimen consisting of dacarbazine, vincristine, bleomycin and
      lomustine in combination with natural leukocyte interferon (IFN)-alpha was
      administered to 48 metastatic melanoma patients with very favorable results. The
      frequencies of peripheral blood lymphocyte subsets during this treatment were
      monitored by flow cytometry in order to elucidate the underlying antitumor
      mechanism. Analysis of 467 peripheral blood samples revealed a significant
      decrease during treatment in absolute values of all lymphocyte subsets (CD4, CD8,
      CD56) as well as in total lymphocyte count. All the values returned to normal
      after discontinuation of treatment. Significant alterations in proportions of
      lymphocyte subsets were detected. Notably, the CD4+/CD8+ ratio showed changes
      related to response, treatment duration, and disease progression. Exceptionally
      high CD4+/CD8+ ratios (up to 14) were observed soon after the start of treatment
      in some of the patients later achieving a complete response. During the course of
      treatment, in 76% of the patients receiving at least a 2-month treatment, the
      CD4+/CD8+ ratio decreased to less than 1.0. Peculiarly, the nadir CD4+/CD8+ ratio
      was consistently observed 1-6 months before clinically detectable disease
      progression, suggesting a relation between CD4+/CD8+ ratio and tumor control.

PMID- 7509189
TI  - Effects of amino acid replacements on the reductive unfolding kinetics of
      pancreatic trypsin inhibitor.
AB  - In order to characterize the major transition states in the disulfide-coupled
      folding pathway of bovine pancreatic trypsin inhibitor (BPTI), the reductive
      unfolding kinetics of wild-type BPTI and 18 variants with single amino acid
      replacements were measured in the presence of varying concentrations of
      dithiothreitol (DTTSHSH). As observed previously for the wild-type protein,
      unfolding of the mutant proteins was found to proceed through the formation of a
      native-like two-disulfide intermediate (NSHSH), followed by either direct
      reduction of this intermediate or intramolecular rearrangement to generate other
      two-disulfide species that were then reduced further. From the dependence of the
      rate of disappearance of NSHSH on the concentration of DTTSHSH, the rate
      constants for the direct and rearrangement mechanisms were estimated. All of the
      amino acid replacements examined were found to increase both rate constants, with
      some mutants unfolding as much as 10,000-fold more rapidly than the wild-type
      protein. The two rate constants were highly correlated by a linear free energy
      relationship, suggesting that the transition states for the direct and
      rearrangement mechanisms are very similar in their response to amino acid
      replacements. These results are consistent with a model in which the two
      transition states, which are also the major transition states for disulfide
      coupled refolding, are extensively unfolded.

PMID- 7509190
TI  - Identification of a lipolysis-stimulated receptor that is distinct from the LDL
      receptor and the LDL receptor-related protein.
AB  - This paper provides further characterization of a receptor that, in cells lacking
      the LDL receptor (FH fibroblasts), mediates lipoprotein binding, uptake, and
      degradation when incubated with oleate at concentrations not exceeding albumin
      binding capacity. This oleate-activated receptor is genetically distinct from the
      LDL receptor and is hereafter referred to as the lipolysis-stimulated receptor
      (LSR). Its apparent affinity was higher for triglyceride-rich lipoproteins
      (chylomicrons, VLDL) and for lipid emulsions supplemented with recombinant apoE,
      than for LDL which contains solely apoB. In contrast, VLDL isolated from a Type
      III hyperlipidemic patient (apoE2/2 phenotype) failed to bind to the LSR. Five
      lines of evidence indicated that the LSR is distinct from the LDL receptor
      related protein (LRP): (1) the LRP ligand, alpha 2-macroglobulin-methylamine
      (alpha 2-MG*), did not bind to the oleate-induced LDL binding site; (2) oleate
      had no effect on the binding of alpha 2-MG* to LRP; (3) the LRP-associated
      protein, RAP, which inhibits LRP, had no effect on the LSR; (4) binding of
      lipoproteins to LSR was independent of Ca2+; and (5) LSR activity resolved as two
      proteins smaller than LRP (apparent molecular masses as determined by ligand
      blots: 115 and 85 kDa). That LSR provides a new candidate receptor contributing
      to the clearance of chylomicron remnants (CMR) is supported by the observation
      that LSR was inhibited by lactoferrin, a milk protein that delays CMR clearance
      when injected in vivo. Furthermore, in primary cultures of rat hepatocytes,
      oleate stimulated binding, uptake, and degradation of LDL with kinetic
      characteristics similar to that of LSR expressed in FH fibroblasts.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7509191
TI  - Interhelix geometry of stems I and II of a self-cleaving hammerhead RNA.
AB  - In order to investigate the geometry of a self-cleaving hammerhead domain, an RNA
      heteroduplex has been constructed in which two of the three helix stems of the
      domain have each been elongated to 76 duplex base pairs (bp), resulting in an RNA
      molecule of ca. 160 bp. The heteroduplex molecule is capable of undergoing self
      cleavage at neutral pH, upon addition of either Mg2+ or Mn2+, but does not
      dissociate following cleavage. Using a combination of electrophoretic and
      hydrodynamic methods, as employed earlier to define the geometry of a four-way
      DNA branch [Copper & Hagerman (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 7336
      7340], we have determined that the elongated hammerhead stems are nearly
      collinear prior to self-cleavage. Following self-cleavage, and in the absence of
      Mg2+, the angle between the two stems becomes much more acute and/or flexible;
      however, in the presence of Mg2+, the cleaved structure appears to retain the
      geometry of the precleaved form (at least with respect to the interstem angle).
      It is also observed that the self-cleavage reaction is promoted by Mn2+ to a much
      greater extent than by Mg2+, consistent with earlier observations. Finally,
      although the elongated helices appear to be nearly collinear in the uncleaved
      molecule, the electrophoretic mobility of that species is dramatically reduced
      with respect to linear control RNAs, indicating that caution should be exercised
      in the quantitative assignment of branch angles solely from gel retardation
      experiments.

PMID- 7509192
TI  - Electropermeabilization of cells in tissues assessed by the qualitative and
      quantitative electroloading of bleomycin.
AB  - Using cells in suspension, electropermeabilization is a technique extensively
      used to transfect living cells or to introduce a variety of compounds inside the
      cells. Here we demonstrate the reality of the tissue electropermeabilization
      using qualitative and quantitative determinations of the electroloading of
      bleomycin considered as an nonpermeant molecule that serves as an indicator of
      the permeabilization. In tissues, cell electropermeabilization is achieved for
      electric field intensities lower than those necessary to permeabilize the same
      cells in suspension. We also emphasize the importance of the geometry of the
      electric field lines defined by the electrodes for permeabilizing a whole tissue,
      for example a tumor.

PMID- 7509193
TI  - Interaction of multidrug-resistant Chinese hamster ovary cells with the peptide
      ionophore gramicidin D.
AB  - A major form of multidrug resistance results from the overexpression of P
      glycoprotein, a 170 kDa membrane protein. Multidrug resistant (MDR) Chinese
      hamster ovary (CHO) cells and mdrl transfectants displayed cross-resistance to
      the channel-forming peptide ionophore gramicidin D, which was reversed by various
      chemosensitizers, thus directly implicating P-glycoprotein as the mediator of
      resistance. However, gramicidin D was not able to inhibit [3H]azidopine
      photolabelling of P-glycoprotein. MDR cells were not resistant to other pore
      forming ionophores, but showed a modest level of cross-resistance to the mobile
      ionophore valinomycin. There was no difference in 125I-gramicidin D uptake by
      resistant and sensitive cells. Resistant cells showed lower 86Rb+ uptake,
      relative to the drug-sensitive parent. Addition of GmD increased both the rate
      and the level of 86Rb+ uptake in sensitive cells, but had no effect on MDR cells.
      MDR cells also showed much lower rates of gramicidin D-dependent 86Rb+ efflux
      than sensitive cells, and this was greatly increased by verapamil. These results
      suggest that P-glycoprotein interferes with the formation of ion-conducting
      gramicidin D channels. In contrast, valinomycin had the same effect on gramicidin
      D-dependent cation efflux in MDR and sensitive cells. Gramicidin D is thus unique
      among the ionophores is being a substrate for P-glycoprotein, which appears to
      greatly reduce the formation of active dimeric channels in the plasma membrane of
      MDR cells.

PMID- 7509195
TI  - hnRNP-U/SAF-A is encoded by two differentially polyadenylated mRNAs in human
      cells.
AB  - Scaffold attachment factor A (SAF-A; Romig et al. (1992) EMBO J. 11, 3431-3440)
      is a human nuclear protein with high affinity for SAR DNA (scaffold attached
      region; Laemmli et al. (1992) Curr. Opin. Cell. Biol. 2, 275-285). We isolated
      and sequenced two classes of cDNA clones coding for SAF-A and found that their
      coding sequences are identical with the coding sequence of hnRNP-U (Kiledjian and
      Dreyfuss (1992) EMBO J. 11, 2655-2664). The two classes of cDNA clones differ,
      however, in the length of their 3' untranslated region and result from the use of
      two different polyadenylation signals. This is consistent with Northern blotting
      experiments which show that two mRNAs with a length of 3.9 kb and 3.1 kb,
      respectively, exist in human cells. Using selective cDNA fragments as probes we
      show that the shorter mRNA lacks 800 nucleotides of the untranslated 3' end.

PMID- 7509194
TI  - Identification and characterization of the developmentally regulated pattern of
      expression in the testis of a mouse gene exhibiting similarity to the family of
      phosphodiesterases.
AB  - A cDNA for a rat brain phosphodiesterase (PDE) was used to screen a mouse testis
      library to identify the murine PDEs which are expressed in this tissue. A clone
      of 981 bp, p4-6, was isolated and shown to exhibit limited identity at the amino
      acid level to the rat brain PDE (20%). The putative protein encoded by clone p4-6
      also contains multiple potential modification sites, for phosphorylation,
      myristylation, and glycosylation, many of which are located at positions similar
      to those found for rat brain PDE. The gene identified by p4-6 yields 3
      transcripts, an abundant 1.9 kb transcript, and less abundant transcripts of 3.8
      and 6.7 kb. Of the nine tissues examined in this study, the expression of the
      corresponding gene was limited to the adult mouse testis. Furthermore, the
      expression in the testis was most abundant in the germ cell lineage, although low
      levels were detected in somatic cells of the testis as well. Analysis of RNA from
      testes at different stages of development suggested that the p4-6 gene is most
      abundantly expressed in germ cells that have completed the meiotic divisions.

PMID- 7509196
TI  - Developing a poster presentation.
AB  - Poster presentations are one method of presenting articles, projects, or research
      at a professional conference. The purpose of this article is to delineate the
      development of a poster for presentation. Essential points on topic selection,
      writing the abstract, development strategies, transport, and handout preparation
      are included.

PMID- 7509197
TI  - The distribution of astrocytes, oligodendroglia and myelin in normal and
      transplanted rat superior colliculus: an immunohistochemical study.
AB  - Immunohistochemical methods have been used to determine the distribution of
      macroglia and myelin in the normal rat superior colliculus (SC) and in grafts of
      fetal tectal tissue. The fetal tissue was derived from 15 day-old (E15) rat
      embryos and was transplanted onto the midbrain of newborn host rats of the same
      (PVG/c) strain. Antibodies to glial fibrillary acidic protein (GFAP) and carbonic
      anhydrase II (CAII) were used to visualize astrocytes and oligodendroglia
      respectively. Myelin was immunostained with antibodies to either proteolipid
      protein (PLP) or myelin basic protein (MBP). In the normal SC, GFAP positive
      astrocytes were found scattered throughout the SC, particularly in the
      superficial layers. They were especially prominent at the pial surface, around
      major blood vessels and at the midline between the two colliculi. CAII
      immunoreactive oligodendroglia and associated myelin were also found throughout
      the SC; by far the lowest density was seen in the stratum griseum superficiale
      (SGS). Both types of macroglia cell were found in abundance in tectal
      transplants, indicating that the precursors of these glial types were present in
      the E15 rat mesencephalon. In mature grafts, large numbers of fibrous astrocytes
      were found throughout the neuropil and the level of GFAP immunoreactivity was
      consistently greater than in host SC. Astrocytes seemed to be maintained in a
      reactive, perhaps immature state within the grafted tissue. Tectal transplants
      possessed large numbers of fully differentiated CAII-positive oligodendroglia and
      the grafts contained a dense network of myelinated axons. However the
      distribution of CAII and PLP immunoreactivity was not homogeneous; there were
      localized, well-defined regions that contained few oligodendroglia and relatively
      little myelin. These areas stained intensely for acetylcholinesterase (AChE) and
      were almost certainly homologous to the SGS of normal SC. The relative lack of
      oligodendroglia in the AChE stained patches in grafts and in SGS in situ suggests
      that local factors influencing the proliferation and distribution of
      oligodendroglia in normal SC may have been operating in a similar manner within
      the tectal transplant neuropil.

PMID- 7509198
TI  - 6-[18F]fluoro-L-dopa and cerebral blood flow in unilaterally MPTP-treated
      monkeys.
AB  - Intravenous administration of 15O-labeled water and 6-[18F]-L-fluorodopa were
      used to assess abnormal striatal activity in monkeys after long-term recovery of
      unilateral lesions of the dopaminergic nigro-striatal system induced by the
      neurotoxin MPTP. PET data were examined in relation to behavioral and biological
      parameters. Cerebral blood flow and 6-[18F]-L-DOPA uptake were found to be
      significantly reduced in the lesioned striatum, compared to the unaffected side
      and to normal controls. There was no correlation between cerebral blood flow and
      any of the behavioral parameters. The uptake rate constant of 18F-DOPA from blood
      to striatum and the ratios of striatum to occipital areas were highly correlated
      to the concentrations of homovanillic acid in the cerebrospinal fluid of the same
      animals but not to the rotational behavior. This MPTP-induced model of striatal
      dopamine deficiency in primates presents similarities with idiopathic Parkinson's
      disease and may be used to evaluate the effects of dopaminergic lesions and
      transplants on brain function.

PMID- 7509199
TI  - Restricted migration of transplanted oligodendrocytes or their progenitors,
      revealed by transgenic marker M beta P.
AB  - Transgenic mice of line M beta P3 express bacterial beta-galactosidase in
      oligodendrocytes but not other cells of the CNS. The marker enzyme, demonstrated
      histochemically or by immunostaining in oligodendrocyte cell bodies and along
      myelin internodes, appears at the time of myelination and persists thereafter; in
      transplantation experiments, the marker may serve to indicate both the source of
      particular cells and their state of differentiation. The subventricular zone of
      the lateral ventricle, grafted from transgenic to wild-type perinatal recipient
      mice, yields histochemically labeled oligodendrocytes in surrounding host tissue.
      When grafts are placed in cerebral cortex near callosal radiations, graft-derived
      oligodendrocytes are found in cerebral cortex and subcortical white matter as far
      as 1.5 mm from the site of implant but not in nearby caudoputamen. This study is
      the first to document differentiation of transplant-derived oligodendrocytes in
      normal developing CNS. Our results are consistent with the well-established
      notion that oligodendrocyte progenitors migrate during normal development and
      suggest that such migration might be guided or restricted by mechanisms yet to be
      identified.

PMID- 7509200
TI  - Perinatal management of idiopathic thrombocytopenic purpura in pregnancy: risk
      factors for passive immune thrombocytopenia.
AB  - Thirty-nine pregnant women with idiopathic thrombocytopenic purpura (ITP) were
      studied in order to evaluate the influence of therapies for maternal ITP on fetal
      passive immune thrombocytopenia (PIT). Neonatal platelet counts were also
      compared with platelet counts, amount of PAIgG, and presence of circulating
      antiplatelet antibody in maternal blood. Eight of 41 neonates (19.5%) presented
      PIT without neonatal mortality. A higher incidence of PIT was observed in women
      with prior splenectomy than in women without splenectomy (66.7% vs 11.4%).
      Neither a therapeutic effect nor an increased risk of PIT was observed with
      steroids or gammaglobulin administration. No correlation was found between
      neonatal platelet counts and maternal platelet counts or maternal PAIgG, while
      positive cases for circulating antiplatelet antibody assay presented a higher
      incidence of PIT than negative cases. Additionally, a higher incidence of PIT was
      observed in women with a history of previous PIT than in women with a history of
      normal delivery. Prior splenectomy, presence of antiplatelet antibody in maternal
      blood, and a history of previous PIT seem to be risk factors for fetal PIT.

PMID- 7509201
TI  - Conformation of the oligosaccharide receptor for E-selectin.
AB  - A tetrasaccharide related to the blood group oligosaccharides, known as sialyl
      LewisX, has been proposed as the receptor for the lectin responsible for
      leukocyte adhesion named alternatively as E-selectin or ELAM-1. The 13C- and 1H
      nmr spectra have been completely assigned for a tetrasaccharide model of this
      receptor, Neu5Ac alpha-(2-->3)-Gal beta-(1-->4)-[Fuc alpha-(1-->3)-]GlcNAc beta
      NHAc. Quantitative nuclear Overhauser data (NOESY) have been recorded and
      analyzed by a complete spin matrix simulation method. Conformational space was
      exhaustively searched and all conformational models whose simulated NOESY spectra
      matched the experiment were found. Molecular mechanics and molecular dynamics
      calculations were carried out to test whether the experimental conformations are
      low energy and thus likely to represent true single conformations for the
      tetrasaccharide. It was concluded that while the LewisX trisaccharide portion of
      the compound adopts a single conformation, there is likely to be some flexibility
      about the Neu5Ac alpha-(2-->3)-linkage. A model featuring fast exchange between
      two different conformations of this linkage is found to be consistent with both
      the nmr experiments and the molecular dynamics simulations.

PMID- 7509202
TI  - The interaction of substituted 2-phenylquinoline intercalators with
      poly(A).poly(U): classical and threading intercalation modes with RNA.
AB  - The interaction of a series of 2-phenylquinoline derivatives with RNA was
      investigated by means of viscometric, pKa, spectroscopic, binding, Tm, and
      kinetic methods. Compounds 1, 2, and 3 have a piperazyl substituent at the para,
      meta, or ortho position, respectively, while 4 has an unsubstituted phenyl ring.
      The pKa results suggest that 1 has three charges, 2 and 3 have more than two
      charges, and 4 has two charges at pH 6.2. Spectroscopic and Tm results indicate
      that 1 binds more strongly to RNA than 2-4. Kinetic and modeling results indicate
      that 1 is a threading intercalator while 2 and 4 are classical intercalators. All
      experimental results indicate that 3, which has a large twist between the phenyl
      and quinoline rings, binds weakly with RNA.

PMID- 7509203
TI  - Partial cDNA cloning and NGF regulation of a rat 5-HT3 receptor subunit.
AB  - Nerve growth factor (NGF) stimulates 5-HT3 receptor expression although the
      mechanism(s) responsible for this effect are unknown. We report the nucleotide
      and deduced amino acid sequences of a nearly complete rat 5-HT3 receptor subunit
      and use the sequence to develop a reverse transcription-polymerase chain reaction
      (RT-PCR) assay that measures 5-HT3 mRNA. Exposure of PC12 cells to NGF results in
      increasing steady-state levels of 5-HT3 mRNA. The four-fold increase in mRNA
      correlates with and is sufficient to account for increases in receptor measured
      by agonist induction of whole cell currents.

PMID- 7509204
TI  - Pontomedullary neurons transsynaptically labeled by laryngeal pseudorabies virus.
AB  - The activity of the laryngeal abductor, the posterior cricoarytenoid (PCA)
      muscles, is diminished with the loss of wakefulness. During sleep, PCA muscles
      become hypotonic, suggesting that neural mechanisms which control states of
      consciousness also contribute to state-dependent changes in upper airway patency.
      The medial pontine reticular formation (mPRF) has long been known to play a key
      role in sleep control. Microinjection of cholinergic agonists into the mPRF
      produces a rapid eye movement (REM) sleep-like state and PCA muscle hypotonia,
      but the neuroanatomical pathways mediating this hypotonia are not clear.
      Therefore, the present study used retrograde transsynaptic viral labeling to
      define multisynaptic pathways from the PCA muscles to the mPRF. Pseudorabies
      virus was injected into the laryngeal PCA muscles of anesthetized rats. The
      distribution of retrogradely labeled neurons was studied in the brain stem 4 days
      post-inoculation. The results show that brain stem areas known to be involved in
      sleep cycle control are part of a multisynaptic pathway providing input to the
      laryngeal PCA muscles.

PMID- 7509205
TI  - Lack of involvement of nitric oxide in NMDA-induced neuronal cell death in
      cortical culture.
AB  - In primary cultures of rat cerebral cortex, N-methyl-D-aspartate causes
      widespread neurotoxicity. Inhibitors of the nitric oxide generating the enzyme
      nitric oxide synthase has been shown to attenuate the effects of N-methyl-D
      aspartate in a number of neuronal systems both in vivo and in vitro. In our
      experiments, the nitric oxide synthase inhibitor N-nitroarginine was ineffective
      at blocking neurotoxicity induced by N-methyl-D-aspartate. Cyclic guanine
      monophosphate, known to be synthesized in response to nitric oxide was
      demonstrably inhibited by identical treatments with N-nitroarginine in sister
      cultures. We conclude that although nitric oxide is produced in response to N
      methyl-D-aspartate, it is neither necessary nor sufficient for neurotoxicity.

PMID- 7509206
TI  - Palindromic repeated sequences (PRSs) in the mitochondrial genome of rice:
      evidence for their insertion after divergence of the genus Oryza from the other
      Gramineae.
AB  - We have identified a family of small repeated sequences (from 60 to 66 bp in
      length) in the mitochondrial genome of rice (Oryza sativa cv. Nipponbare). There
      are at least ten copies of these sequences and they are distributed throughout
      the mitochondrial genome. Each is potentially capable of forming a stem-and-loop
      structure and we have designated them PRSs (palindromic repeated sequences).
      Their features are reminiscent of the small dispersed repeats in the
      mitochondrial DNA (mtDNA) of some lower eukaryotes, such as Saccharomyces
      cerevisiae, Neurospora crassa and Chlamydomonas reinhardtii. Some of the PRSs of
      rice mtDNA are located in the intron of the gene for ribosomal protein S3 (rps3)
      and in the flanking sequence of the gene for chloroplast-like tRNA(Asn) (trnN).
      analysis of PCR-amplified fragments of these regions from the DNA of some
      Gramineae suggests that the PRSs were inserted into these regions of the Oryza
      mtDNA after the divergence of Oryza from the other Gramineae.

PMID- 7509207
TI  - Steel factor and c-kit regulate cell-matrix adhesion.
AB  - Steel (SI) and white spotting (W) loci encode steel factor (c-kit ligand) and the
      c-kit tyrosine kinase receptor, respectively. Mutations at these loci affect
      migration and differentiation of primordial germ cells, neural crest-derived
      melanoblasts, and hematopoietic cells. In these processes, cell adhesion
      molecules are hypothesized to be crucial. We have examined the role of steel
      factor and c-kit in cell-extracellular matrix adhesion using bone marrow-derived
      mast cells as a model system. Steel factor stimulates mast cells to bind to
      fibronectin and, to a lesser extent, to vitronectin, whereas interleukin-3 and
      interleukin-4, which are also mast cell growth factors, do not. Activation of
      adhesiveness is transient, occurs at concentrations of steel factor 100-fold
      lower than required for growth stimulation, and requires the integrin VLA-5. Mast
      cells from c-kit mutant mice adhere to fibronectin on stimulation with phorbol 12
      myristate 13-acetate (PMA), but not on stimulation with steel factor, indicating
      that stimulation of integrin adhesiveness requires activation of the c-kit
      protein tyrosine kinase. By contrast, c-kit mutant and wild-type mast cells
      adhere equally well to COS cells expressing membrane-anchored steel factor,
      showing that the kinase activity of c-kit is not required for adhesion directly
      mediated by c-kit. Our findings suggest that regulation of adhesion is an
      important biologic function of steel factor.

PMID- 7509210
TI  - Lymphoma regression induced by monoclonal anti-idiotypic antibodies correlates
      with their ability to induce Ig signal transduction and is not prevented by tumor
      expression of high levels of bcl-2 protein.
AB  - Custom-made monoclonal anti-idiotype antibodies (anti-Id MoAbs) have been tested
      as a treatment modality in 34 non-Hodgkin's lymphoma (NHL) patients. Partial or
      complete tumor remissions have been induced with this treatment in 68% of these
      patients. One mechanism by which anti-idiotype antibodies may have induced these
      tumor responses is via a direct antiproliferative effect on the tumor cells,
      resulting in apoptosis. Primary NHL cells do not proliferate well enough in vitro
      to test this hypothesis directly. Therefore, we studied the effect of anti
      idiotype antibodies on signal transduction through the surface Ig receptor as
      measured by the induction of cellular protein tyrosine phosphorylation. To assess
      whether bcl-2 protein could protect lymphoma cells from death induced by anti-Id
      MoAb, we also measured the level of bcl-2 protein in the same tumor cells. We
      found a strong correlation between the ability of an anti-Id MoAb to induce an
      increase in tyrosine phosphorylation in vitro and its ability to induce a tumor
      regression in the patient. By contrast, the level of bcl-2 expressed by the tumor
      cells was not correlated with clinical response to anti-Id MoAb treatment.

PMID- 7509209
TI  - A cautionary note regarding hydroxyurea in sickle cell disease.
AB  - Hydroxyurea can increase fetal hemoglobin (HbF) and improve the clinical course
      of sickle cell disease (SCD) patients. However, several issues of hydroxyurea
      therapy remain unresolved, including differences in patients' drug clearance,
      predictability of drug response, reversibility of sickle cell disease-related
      organ damage by hydroxyurea, and the efficacy of elevated HbF. We treated two
      patients with hydroxyurea for periods of 1 to 4 years, monitoring clinical course
      and laboratory parameters at regular intervals. The first patient (patient A) had
      a history of chronic pain and extensive hospitalizations. The second patient
      (patient B) had a history of stroke and refused to continue with chronic
      transfusion therapy and chelation. Both patients showed a fivefold to tenfold
      increase in HbF (5% to 25%, 3% to 31%). However, patient A developed an acute
      chest syndrome, despite an HbF level of 20%. After red blood cell transfusions
      for hypoxia, the HbF level decreased to 5%. When hydroxyurea dosage was
      increased, pancytopenia developed and was not resolved until 2 months after
      hydroxyurea was discontinued; Patient B developed a cerebral hemorrhage on
      hydroxyurea; he died shortly thereafter. His HbF level was 21% before death. We
      noted an increase in HbF and a general improvement in the two patients. However,
      both experienced major SCD-related complications despite HbF levels over 20%. Our
      findings also suggest that the progressive vascular changes associated with SCD
      are unlikely to be dramatically affected by increased HbF levels. Because neither
      the efficacy nor the toxicity of hydroxyurea have been thoroughly investigated,
      physicians should be cautious in prescribing hydroxyurea for patients with SCD
      before completion of the National Clinical Trial.

PMID- 7509208
TI  - Preferential usage of the bone-type leader sequence for the transcripts of
      liver/bone/kidney-type alkaline phosphatase gene in neutrophilic granulocytes.
AB  - Alkaline phosphatase in neutrophils (NAP) is a product of the liver/bone/kidney
      type alkaline phosphatase gene, the chromosomal structure of which has recently
      been analyzed. The gene has two alternative leader sequences resulting in the two
      types of mRNA (liver-type and bone-type mRNAs), which suggests that the
      expression of the gene is regulated by independent promoters. To determine the
      mechanism underlying NAP induction, it is essential to know which type of the
      mRNAs is dominant in neutrophils. We adopted quantitative polymerase chain
      reaction method to determine the relative amount of bone-type mRNA in
      neutrophils. The bone-type mRNA was found to be at least 5 times more than the
      liver-type mRNA. mRNA of NAP is known to be induced by in vitro treatment of the
      cells with granulocyte colony-stimulating factor (G-CSF), which is enhanced by a
      simultaneous addition of retinoic acid. In neutrophils treated with G-CSF, the
      bone-type mRNA was at least 6 times more than the liver-type mRNA. In neutrophils
      treated by both G-CSF and retinoic acid, the bone-type mRNA was at least 22 times
      more than the liver-type mRNA. The results show that the bone-type mRNA is
      predominantly transcribed in peripheral neutrophils and in neutrophils cultured
      in vitro.

PMID- 7509211
TI  - Stem cell factor and basic fibroblast growth factor are synergistic in augmenting
      committed myeloid progenitor cell growth.
AB  - Stem cell factor (SCF) and basic fibroblast growth factor (bFGF) are
      hematopoietic cytokines produced by bone marrow stromal cells. It is known that,
      although SCF and bFGF have limited clonogenic activity on their own, they can
      augment colony-stimulating factor (CSF)-mediated progenitor cell growth. Because
      these factors are both sequestered by stromal cells, we examined their
      interaction on progenitor cell growth in conjunction with granulocyte-macrophage
      CSF (GM-CSF). In this study, we show that clonogenic growth derived from low
      density bone marrow cells stimulated by GM-CSF is significantly augmented (P <
      .001) in the presence of maximal (100 ng/mL) concentrations of SCF in combination
      with 100 ng/mL of bFGF. When CD34+ cells are used, the synergistic effect of bFGF
      and SCF for GM-CSF-mediated progenitor cell growth is further increased,
      resulting in as much as a sevenfold increase in detectable colony-forming units
      granulocyte-macrophage (P < .001). These data suggest that the synergistic
      activity of bFGF and SCF is mediated directly on hematopoietic precursors. These
      observations suggest that bFGF and SCF, concentrated locally on stromal cell
      surfaces, might interact in concert with other hematopoietic cytokines to
      regulate stem cell proliferation and differentiation in hematopoietic niches in
      the bone marrow.

PMID- 7509212
TI  - Characterization of cultured mast cells derived from Ws/Ws mast cell-deficient
      rats with a small deletion at tyrosine kinase domain of c-kit.
AB  - The Ws mutant allele of rats represents a 12-base deletion at the tyrosine kinase
      domain of the c-kit gene. Although homozygous Ws/Ws rats were deficient in both
      connective tissue-type mast cells (CTMC) and mucosal-type mast cells (MMC), mast
      cells did develop when bone marrow cells of Ws/Ws rats were cultured in the
      presence of concanavalin A-stimulated spleen cell conditioned medium (ConA-SCM).
      Although the proliferative response of rat cultured mast cells (RCMC) derived
      from Ws/Ws rats to ConA-SCM was comparable to that of RCMC derived from control
      normal (+/+) rats, the proliferative response of Ws/Ws RCMC to rat recombinant
      stem cell factor (rrSCF; a ligand for the c-kit receptor tyrosine kinase) was
      much lower than that of +/+ RCMC. However, a slight c-kit kinase activity was
      detectable in Ws/Ws RCMC, and the proliferation of Ws/Ws RCMC was accelerated
      when rrSCF was added to ConA-SCM. Because CTMC contain rat mast cell protease-I
      (RMCP-I) and MMC contain RMCP-II, the phenotype of +/+ and Ws/Ws RCMC in various
      culture conditions was evaluated by immunohistochemistry of RMCPs. Both +/+ and
      Ws/Ws RCMC showed the MMC-like phenotype (RMCP-I-/II+) when they were cultured
      with ConA-SCM alone. Most +/+ RCMC and about half of Ws/Ws RCMC acquired a novel
      protease (RMCP-I+/II+) phenotype when they were cultured with rrSCF alone.
      However, because the number of Ws/Ws RCMC dropped to one-tenth in the medium
      containing rrSCF alone, the absolute number of Ws/Ws RCMC with the RMCP-I+/II+
      phenotype did not increase significantly. The effect of rrSCF in inducing the
      novel phenotype was suppressed when ConA-SCM was added to rrSCF. In contrast, +/+
      and Ws/Ws RCMC cocultured with +/+ fibroblasts showed the RMCP-I+/II+ phenotype
      even in the presence of ConA-SCM. Moreover, a fibroblast cell line derived from
      SI/SI mouse embryos that did not produce SCF did not support the survival of both
      +/+ and Ws/Ws RCMC but did induce the RMCP-I+/II+ phenotype in about half of +/+
      and Ws/Ws RCMC when their survival was supported by the addition of ConA-SCM. The
      normal signal transduction through the c-kit receptor did not appear to be
      prerequisite for the acquisition of the RMCP-I+/II+ phenotype.

PMID- 7509213
TI  - Proliferative but not nonproliferative responses to granulocyte colony
      stimulating factor are associated with rapid activation of the p21ras/MAP kinase
      signalling pathway.
AB  - Granulocyte colony-stimulating factor (G-CSF) can elicit responses that include
      proliferation, granulocytic differentiation, and activation of cellular functions
      in target cells. The biochemical pathways responsible for transduction of these
      signals from the G-CSF receptor (G-CSFR) have not been defined. In this report,
      we show that, in murine (NFS-60) and human (OCI-AML 1) myeloid leukemia cell
      lines and in murine pro-B-lymphocytic cells, BAF/B03, transfected with the murine
      G-CSFR, proliferative responses to G-CSF are associated with rapid activation of
      p42 and p44 MAP kinases and p21ras. Truncation of the cytoplasmic portion of the
      murine G-CSFR at residue 646 but not at residue 739 abolished G-CSF-induced
      stimulation of cellular proliferation as well as activation of MAP kinase and
      p21ras in transfected BAF/B03 cells. G-CSF-induced granulocytic differentiation
      of the murine leukemic cell line 32DC13(G) occurred in the absence of detectable
      activation of p42 MAP kinase. Nonproliferative responses to G-CSF in the human
      promyelocytic cell line HL-60 and in human neutrophils were similarly associated
      with no MAP kinase activation. These results imply that differing cellular
      effects of G-CSF may be involve the recruitment of differing signal transduction
      pathways with the p21ras/MAP kinase pathway being limited to proliferative
      responses.

PMID- 7509214
TI  - Production of hematopoietic stem cell-chemotactic factor by bone marrow stromal
      cells.
AB  - Chemotactic factors produced by stromal cells in the bone marrow are
      characterized. Two kinds of factors produced by stromal cell lines are identified
      using blind-well Boyden's Chambers; one is a neutrophil-chemotactic factor and
      the other a hematopoietic stem cell (HSC)-chemotactic factor. The latter attracts
      blastic cells in a low-density fraction, which are Thy1lo, wheat germ agglutinin
      (WGA)hi, H-2Khi, Ly-1-, Ly-2-, L3T4-, Ly5-, and slg-. The molecular weight of
      this HSC-chemotactic factor is estimated to be more than 200 kD. Putative
      cytokines and growth factors, such as granulocyte colony-stimulating factor
      (CSF), macrophage CSF, granulocyte-macrophage CSF, stem cell factor (SCF),
      interleukin (IL)-6, and IL-3, do not possess HSC-chemotactic activity. These
      findings strongly suggest that bone marrow stromal cells produce a new factor
      that attracts HSCs.

PMID- 7509215
TI  - Induced expression of c-fms in normal hematopoietic cells shows evidence for both
      conservation and lineage restriction of signal transduction in response to
      macrophage colony-stimulating factor.
AB  - Retrovirus-mediated gene transfer was used to obtain expression of the macrophage
      colony-stimulating factor (MCSF) receptor, c-fms, on hematopoietic lineages that
      normally do not express this receptor. Cultures of murine fetal liver cells
      infected with the c-fms retrovirus developed erythroid colonies in cultures
      stimulated with M-CSF. However, these colonies were fewer and less hemoglobinized
      than colonies in parallel cultures stimulated by erythropoietin. Culture of
      isolated clones demonstrated a direct action of M-CSF on erythroid clones.
      Culture of c-fms retrovirus-infected adult murine bone marrow cells showed
      megakaryocyte and novel macrophage-megakaryocyte clones when stimulated by M-CSF.
      Culture of isolated clones again confirmed a direct action of M-CSF on
      megakaryocyte clones. In contrast, M-CSF stimulation of c-fms-infected
      granulocytes and granulocyte progenitor cells did not elicit proliferation,
      enhanced survival, or functional stimulation of granulocytes. These findings
      provide evidence for both conservation and lineage restriction of signal
      transduction in normal hematopoietic cells.

PMID- 7509216
TI  - Growth hormone-binding proteins in plasma.
AB  - Two growth hormone-binding proteins (GHBPs), one with high and the other with low
      affinity, have recently been described in the blood of humans and several other
      species. The high-affinity GHBP represents a circulating fragment of the GH
      receptor, encompassing its extracellular domain. The molecular nature of the low
      affinity GHBP is not known in detail. GHBPs form complexes with circulating GH,
      prolong its biological half-life, restrict its distribution in the body, and
      modulate the binding of GH to receptors in tissues. Their net effect in vivo is
      to enhance GH action. The level of high-affinity GHBP in plasma probably reflects
      receptor concentrations in tissues. The level/activity of GHBP is linked to GH
      action, and several congenital or acquired conditions with altered GHBP levels
      are characterized by parallel changes in GH action (Laron-type dwarfism, pygmy
      dwarfism, malnutrition, obesity, insulin-dependent diabetes mellitus, liver
      cirrhosis, renal insufficiency). The GHBP/receptor level is nutritionally
      regulated, with levels low in undernutrition and high in overnutrition.
      Regulation of lean body mass anabolism/catabolism at the level of the
      GHBP/receptor provides a rational explanation for the derangements in the GH axis
      and their biological consequences (retarded or accelerated somatic growth)
      observed in nutrition disorders.

PMID- 7509219
TI  - Suppression of proliferative responses of lymphocytes to food antigens by an anti
      allergic drug, ketotifen fumarate, in patients with food-sensitive atopic
      dermatitis.
AB  - Experimental studies have shown that ketotifen fumarate inhibits reaginic
      antibody-mediated hypersensitivity reactions. In this study, the proliferative
      responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA) in
      children with atopic dermatitis (AD), who are sensitive to hen's egg, were
      significantly higher than those of healthy children. The proliferative responses
      of PBMCs to OA were dose-dependently inhibited by ketotifen in patients with
      hen's egg-sensitive AD. Moreover, the inhibition resulted from the effects of
      ketotifen on T cells. In contrast, the proliferative responses of PBMCs to
      phytohemagglutinin and tetanus toxoid were not inhibited by ketotifen. These
      results suggest that ketotifen inhibits food antigen-specific proliferative
      responses of PBMCs in patients with food-sensitive AD.

PMID- 7509220
TI  - Influence of glycosphingolipids on the release of histamine and sulfidopeptide
      leukotrienes from human basophils.
AB  - Glycosphingolipids (GSLs) are physiological membrane components known to modulate
      various cellular functions. In order to study their influence on basophil
      mediator release washed leukocytes obtained from allergic asthmatics and
      nonatopics were preincubated with varying concentrations of different GSLs. Cells
      were washed and stimulated with anti-IgE, allergen, and calcium ionophore A23187.
      None of the GSLs induced mediator release by itself. Preincubation with the
      acidic gangliosides GM2, GM3, and GD1a significantly enhanced the release of both
      mediators when stimulated with anti-IgE or allergen but not with calcium
      ionophore A23187. Highest enhancement was seen with ganglioside GM2. Mediator
      release was higher in asthmatics than in nonatopics. The acidic
      galactosylceramide-sulfate (sulfatide) showed a significantly enhanced mediator
      release as well, whereas the neutral GSLs lactosyl ceramide and asialo GM2 did
      not influence mediator release. It is concluded that IgE receptor-dependent
      mediator release could be modulated by acidic GSLs.

PMID- 7509217
TI  - Treatment of isolated growth hormone deficiency type IA due to GH-I gene deletion
      with recombinant human insulin-like growth factor I.
AB  - Biosynthetic insulin-like growth factor I (IGF-I) was administered subcutaneously
      twice a day for one year to a patient with isolated growth hormone deficiency
      (IGHD) type IA with high titres of anti-GH antibody (up to 1:1,000,000). During
      IGF-I therapy he showed good linear growth without any side effects, such as
      hypoglycemia and anti-IGF-I antibody formation. Administration of IGF-I to IGHD
      type IA with poor response to GH therapy appears to have a beneficial effect on
      growth.

PMID- 7509218
TI  - Two- and three-dimensional HCN experiments for correlating base and sugar
      resonances in 15N,13C-labeled RNA oligonucleotides.
AB  - New 2D and 3D 1H-13C-15N triple resonance experiments are presented which allow
      unambiguous assignments of intranucleotide H1'-H8(H6) connectivities in 13C- and
      15N-labeled RNA oligonucleotides. Two slightly different experiments employing
      double INEPT forward and back coherence transfers are optimized to obtain the H1'
      C1'-N9/N1 and H8/H6-C8/C6-N9/N1 connectivities, respectively. The correlation of
      H1' protons to glycosidic nitrogens N9/N1 is obtained in a nonselective fashion.
      To correlate H8/H6 with their respective glycosidic nitrogens, selective 13C
      refocusing and 15N-inversion pulses are applied to optimize the magnetization
      transfers along the desired pathway. The approach employs the heteronuclear one
      bond spin-spin interactions and allows the 2D 1H-15N and 3D 1H-13C-15N chemical
      shift correlation of nuclei along and adjacent to the glycosidic bond. Since the
      intranucleotide correlations obtained are based exclusively on through-bond
      scalar interactions, these experiments resolve the ambiguity of intra- and
      internucleotide H1'-H8(H6) assignments obtained from the 2D NOESY spectra. These
      experiments are applied to a 30-base RNA oligonucleotide which contains the
      binding site for Rev protein from HIV.

PMID- 7509221
TI  - Inhibition of histamine release from RBL-2H3 cells by protein synthesis
      inhibitors.
AB  - Effects of cycloheximide, an inhibitor of protein synthesis, on histamine release
      from RBL-2H3 cells were examined. RBL-2H3 cells sensitized by rat antiserum to
      ascaris extract were challenged by the antigen, and histamine release during a
      period of 30 min was measured. Pretreatment with cycloheximide (1 microgram/ml)
      for 1 h significantly inhibited the antigen-induced histamine release (36%
      inhibition). The cycloheximide-induced inhibition of histamine release was
      abolished when the cells were further incubated in the absence of cycloheximide
      for 2 h. Pretreatment with puromycin (3 and 10 micrograms/ml), an inhibitor of
      protein synthesis, or actinomycin D (0.1-1 microgram/ml), an inhibitor of DNA
      dependent RNA synthesis, also inhibited the antigen-induced histamine release in
      a concentration-dependent manner. Both ionomycin- and thapsigargin-induced
      histamine release were also inhibited by pretreatment with cycloheximide.
      Measurement of intracellular Ca2+ levels using quin 2 revealed that cycloheximide
      inhibits the increase in Ca2+ levels induced by the antigen, ionomycin or
      thapsigargin. These results suggest that histamine release induced by the
      antigen, ionomycin and thapsigargin in RBL-2H3 cells is mediated by protein(s)
      which is newly synthesized and inactivated rapidly, and the newly synthesized
      protein(s) is involved in the increase of intracellular Ca2+ levels induced by
      these stimulants.

PMID- 7509222
TI  - Absence of bcr/abl gene in single hemopoietic progenitors in some patients with
      chronic myelogenous leukemia.
AB  - CD34+DR- and CD34+DR+ cells were isolated from the marrow mononuclear cells of
      five patients with chronic myelogenous leukemia (CML) carrying the Philadelphia
      (Ph) chromosome. Analysis of bcr/abl hybrid mRNA in individual colonies from a
      single cell using reverse transcriptase polymerase chain reaction (RT-PCR)
      demonstrated the presence or absence of the hybrid mRNA. For patient 1 in the
      chronic phase of CML, the hybrid mRNA was detected in all colonies derived from
      CD34+DR+ and CD34+DR- hemopoietic progenitors. In contrast, for patient 2 in the
      chronic phase of CML, the mRNA was detected in all individual colonies from
      CD34+DR+ progenitors but not in any from CD34+DR- progenitors. For patient 3 in
      the chronic phase of CML, the mRNA was detected in all individual colonies from
      CD34+DR+ but in only some of the colonies from CD34+DR- progenitors. For patients
      4 and 5 in the acute crisis of CML, the mRNA was found in a portion of colonies
      from CD34+DR+ and CD34+DR- progenitors. These results indicated that normal
      clones can persist in CD34+DR- progenitors in some patients with CML, even when
      chromosome analysis detects the Ph chromosome in all metaphases of bone marrow
      cells.

PMID- 7509223
TI  - Multilineage response in aplastic anemia patients following long-term
      administration of filgrastim (recombinant human granulocyte colony stimulating
      factor).
AB  - The present multicenter study was undertaken to confirm whether
      filgrastim/recombinant human granulocyte colony stimulating factor (rhG-CSF)
      could mobilize residual multipotential stem cells by its G0-shortening effect in
      patients with aplastic anemia (AA) and induce a multilineage response. Twenty
      seven patients with acquired severe or moderate AA received long-term
      administration (2 to 12+ months) of rhG-CSF in doses from 100 to 400
      micrograms/body/day by s.c. injection or 250 to 1,500 micrograms/body/day by i.v.
      infusion. Twenty-six out of the 27 evaluable patients showed a substantial
      increase in neutrophils associated with a recovery of myeloid precursors in bone
      marrow within one month of therapy. Interestingly, 10 out of the 27 patients
      showed a dramatic improvement in severe anemia after two to ten months of
      therapy. Moreover, severe thrombocytopenia improved after two to four months of
      therapy in three out of these ten patients accompanied by a significant increase
      in megakaryocytes in bone marrow. Clonal cultures of bone marrow cells revealed a
      recovery in myeloid as well as erythroid precursors in most of these ten
      patients. In two patients who showed a trilineage response, mixed and
      megakaryocyte colony formations also recovered. These results suggest that long
      term administration of rhG-CSF mobilizes myeloid, erythroid, megakaryocyte and
      multipotential progenitor cells and induces a multilineage response in some
      patients with AA.

PMID- 7509225
TI  - c-kit ligand augments granulocyte-macrophage colony growth from patients with 5q-
      syndrome.
AB  - In vitro studies may serve as a guide to clinical strategies with cytokines. In
      this study, marrows from 26 patients with myelodysplastic syndrome (MDS) were
      assayed for myeloid progenitor cells in agar gel. Colony stimulating activity was
      provided by the recombinant human colony stimulating factors granulocyte
      macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating
      factor (G-CSF), interleukin 3 (IL-3), fusion protein (FP), c-kit ligand (KL) or
      GM-CSF combined with other cytokines (KL, IL-3). Decreased colony forming units
      granulocyte-macrophage (CFU-GM) were detected in most cases (69%) compared with
      normal controls. Neither FP nor the combination of GM-CSF + IL-3 produced more
      colonies than GM-CSF alone. The number of CFU-GM did not correlate with French
      American British (FAB) class. All marrows (7) from patients with 5q- showed
      augmentation of GM-CSF induced colonies with the addition of KL. In contrast, KL
      augmentation was noted in only 42% of other MDS marrows (p = 0.01). This in vitro
      result suggests that 5q- may predict a group of MDS patients with a likelihood to
      respond to the combination of GM-CSF + KL.

PMID- 7509224
TI  - Promotion of survival and proliferation by interleukin 3, kit-ligand and
      erythropoietin on early and late appearing spleen colony forming units in
      culture.
AB  - We examined the effects of interleukin 3 (IL-3), kit-ligand and erythropoietin
      (EPO) on the survival and growth of early appearing spleen colony forming units
      (CFU-S8) and late appearing CFU-S (CFU-S12) in short-term liquid culture (SLC).
      In the control cultures, without any additive, CFU-S8 and CFU-S12 declined;
      nearly 10% of the initial number of CFU-S still survived by the second day of
      culture. The addition of IL-3 or kit-ligand increased the survival both of CFU-S8
      and CFU-S12, with an increased dose of concentration, at final concentrations of
      10-200 U/ml and 500-50x dilution, respectively. However, only the survival of CFU
      S8 increased when EPO was added up to 10 U/ml, while the frequency of CFU-S12 was
      not higher than in the control culture. The percentage of CFU-S8 and CFU-S12 in
      DNA synthesis, evaluated in 3H-TdR cytocide experiments, increased after one day
      in culture with each of the three factors. The results suggest that all three
      factors stimulated the proliferation of both populations of CFU-S, but the two
      populations showed different patterns of response to each factor; EPO stimulates
      the proliferation of CFU-S12 that differentiate into CFU-S8 that have less
      capacity for self-renewal, while the addition of IL-3 or kit-ligand causes an
      increase in the number of both populations due to the stimulation of an earlier
      stage of stem cell differentiation or self-renewal of CFU-S12. Our experimental
      system (SLC-CFU-S assay) is useful for evaluating the response of hematopoietic
      stem cells to cytokines which promote the in vitro survival and proliferation of
      these cells.

PMID- 7509227
TI  - [Inhibition of protein kinase C with calphostin increases the hydroosmotic effect
      of vasopressin].

PMID- 7509226
TI  - [Cloning and characteristics of murine genes coding for the human GADD45 analog-
      a protein induced in response to DNA damage].

PMID- 7509228
TI  - The major peripheral myelin protein zero gene: structure and localization in the
      cluster of Fc gamma receptor genes on human chromosome 1q21.3-q23.
AB  - We have characterized the human gene encoding the major peripheral myelin protein
      zero (P0) and assigned it, by in situ hybridization, to the q21.3-q23 region of
      human chromosome 1. This region is known to contain a cluster of interspersed
      genes coding for the related human leukocyte receptors of the Fc portion of the
      immunoglobulin G (Fc gamma RI, II, III). This colocalization was refined by the
      finding of a yeast artificial chromosome (YAC) of the Centre d'Etude du
      Polymorphisme Humain (CEPH) library, hybridizing to the P0 and Fc gamma RIIA
      genes, demonstrating their physical linkage. These data may have important
      implications in demyelinating diseases studies like Charcot-Marie-Tooth disease
      type 1B (CMT1B).

PMID- 7509229
TI  - Skipping of exon 9 in CFTR mRNA of human adult and fetal pancreas from non-CF
      individuals.

PMID- 7509230
TI  - A mutational hot spot in keratin 10 (KRT 10) in patients with epidermolytic
      hyperkeratosis.
AB  - Epidermolytic hyperkeratosis (EHK), (bullous congenital ichthyosiform
      erythroderma), is an autosomal dominant human skin disorder. Recently, we and
      others have described mutations in keratins 1 and 10 (K1 and K10) in patients
      with this disease. Structure-function models predict that these mutations would
      impair normal filament assembly and function. We have extended our earlier
      studies to include 8 more incidences of EHK. In half of these families, we were
      unable to locate a mutation within the rod domains of either K1 or K10. However,
      polymorphic restriction site and sequence analysis of the other families revealed
      a mutational hot spot within the 1A alpha-helical segment of K10. These involve
      Arginine to Histidine, Arginine to Cysteine and Arginine to Leucine substitutions
      at residue 10 of the rod domain. Interestingly, mutations in the corresponding
      Arginine residue in keratin K14 have been identified in patients with
      epidermolysis bullosa simplex. The large number of mutations found at this
      position in both keratins K10 and K14 suggests that other epithelia cell
      disorders will be discovered that are caused by the corresponding mutation in
      related type I keratin genes.

PMID- 7509232
TI  - In frame deletion (delta F311) within a short trinucleotide repeat of the first
      transmembrane region of the cystic fibrosis gene.

PMID- 7509231
TI  - Identification of a new splice site mutation (3849 + 1G-->A) in the intron 19 of
      the CFTR gene.

PMID- 7509234
TI  - A novel insertional mutation at exon VII of the myelin proteolipid protein gene
      in Pelizaeus-Merzbacher disease.
AB  - Pelizaeus-Merzbacher disease (PMD) is an X-linked neurological disorder
      characterized by dysmyelination in the central nervous system (CNS). Recently
      mutations of the myelin proteolipid protein (PLP) gene which encodes both PLP and
      its isoform, DM-20 generated by alternative splicing, have been demonstrated in
      PMD patients. We analyzed the seven exons of the PLP gene of a Japanese boy
      affected with PMD by direct sequencing and identified an insertion event in exon
      VII of the PLP gene. This mutation was also present in his carrier mother, but
      was absent in ninety-five X chromosomes of normal Japanese. The frame-shift
      mutation leads to the production of truncated PLP with altered carboxyl terminal
      amino acid sequences, resulting in considerable change of the structure of PLP
      and DM-20 necessary for functional purposes. This is the first report of a
      mutation in exon VII of the PLP gene associated with PMD.

PMID- 7509233
TI  - A second case of variant of Glanzmann's thrombasthenia due to substitution of
      platelet GPIIIa (integrin beta 3) Arg214 by Trp.

PMID- 7509235
TI  - A G to T mutation at a splice site in a case of Pelizaeus-Merzbacher disease.

PMID- 7509236
TI  - Familial genetic defect in a case of leukocyte adhesion deficiency.
AB  - Leukocyte adhesion deficiency (LAD) is an inherited immunodeficiency disorder
      caused by CD18 subunit abnormality dependent defective expression of beta 2
      integrins on the surface of leukocytes. On analysis of the CD18 molecular defect
      in a female Japanese patient with a severe deficiency LAD phenotype, neither
      CD11a nor CD18 molecules could be detected on the patient's EBV-transformed B
      lymphoblastoid cell line. The mRNA of the patient's B cells was normal in size,
      but was diminished in quantity, to approximately half normal levels. Sequencing
      of the CD18 cDNA of the patient revealed a C605 to T transition, resulting in a
      Pro178-->Leu substitution. This was heterozygous in the genomic DNA, and shown to
      be of maternal origin by family study. Only a few transcripts from the other
      allele without the Pro178-->Leu mutation were detectable. Northern blot analysis
      revealed reduced CD18 mRNA levels, not only in the patient, but also in the
      father and brother. These results indicate that our case is a compound
      heterozygote with two different mutant alleles: one causing a single amino acid
      substitution and the other causing defective expression of mRNA.

PMID- 7509237
TI  - Complex mutation 4114 ATA-->TT in exon 22 of the cystic fibrosis gene CFTR.

PMID- 7509238
TI  - Hepatitis B outbreak in a drug trials unit: investigation and recommendations.
AB  - In autumn 1990 three young men developed acute hepatitis B. They belonged to a
      group of 24 young male volunteers who had taken part in a trial in a residential
      unit for drug trials in July and August 1990. A further case of acute hepatitis B
      and a carrier of hepatitis B e antigen (HBeAg) were detected by serological
      testing of the volunteers. Volunteers, in two groups of twelve, had occupied the
      unit at different times during the trial. The four cases occurred in the group
      that contained the HBeAg positive carrier. The carrier had also taken part in two
      trials on the unit in 1989. He was HBeAg positive then, but transmission of
      hepatitis B virus (HBV) did not occur. Although blood samples were taken in each
      of the three trials, intravenous cannulas were used only in the 1990 trial. It is
      likely that HBV was transmitted by blood to blood contact between volunteers when
      blood was sampled through cannulas during the trial. This outbreak might have
      been prevented. If an infection control policy had been applied to avoid
      hazardous practices, and volunteers had been screened for HBV before entry and
      the carrier excluded (as recommended by the Association of Independent Clinical
      Research Contractors), the outbreak would not have occurred. Volunteers for drug
      trials in residential units should be screened for HBV, human immune deficiency
      virus (HIV) and hepatitis C virus (HCV), and those found to be infected should
      not be accepted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509239
TI  - Hantavirus infections and outbreaks in 1993.
AB  - Hantaviruses are the cause of a worldwide zoonosis and pose a potential threat to
      those exposed to rodents through occupation or recreation. An increased number of
      hantavirus infections was reported in Holland and Germany in the summer of 1993
      and a previously unrecognised hantavirus has been implicated in the pulmonary
      syndrome hantavirus (PSHV) outbreak in the United States. Surveillance data for
      the United Kingdom are limited and infections with hantaviruses are not always
      recognised: hantavirus antibodies have been detected in several groups at risk
      through occupation. It is possible to increase the number of cases detected if
      clinicians familiarise themselves with the symptoms and signs of hantavirus
      infection.

PMID- 7509240
TI  - A pseudo outbreak of tuberculosis.
AB  - Three cases of suspected tuberculosis were diagnosed over a ten day period at an
      oncology unit. Case finding was carried out and six further cases were diagnosed.
      However, doubts were raised about these diagnoses and a review of the outbreak
      investigation was carried out. Investigation of laboratory procedures found that
      the 'outbreak' was likely to be due to a contaminated phenol red solution. This
      incident highlights the importance of a critical evaluation of outbreak
      investigations, and the need for close collaboration between clinicians,
      epidemiologists and laboratory staff.

PMID- 7509241
TI  - Influenza in England and Wales: activity declines.

PMID- 7509242
TI  - Men's health issues.

PMID- 7509243
TI  - Terazosin in the treatment of benign prostatic hyperplasia. Terazosin Benign
      Prostatic Hyperplasia Study Group.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of terazosin, a long-acting
      selective alpha 1-receptor antagonist, in patients with benign prostatic
      hyperplasia. DESIGN AND SETTING: Randomized, double-blind, multicenter (eight
      government and private facilities), placebo-controlled study. PATIENTS: Men aged
      45 years or older, with qualifying signs and symptoms of benign prostatic
      hyperplasia (n = 160). INTERVENTIONS: Terazosin or placebo once daily, with
      terazosin dosage titrated to the patient's response. After a 4-week placebo lead
      in, 1 to 10 mg of terazosin or placebo was administered for 24 weeks. OUTCOME
      MEASURES: Decreases in mean Boyarsky scores for obstructive and irritative
      symptoms and total scores and increases in peak urine flow rate. RESULTS:
      Terazosin-treated patients had decreases in Boyarsky obstructive, irritative, and
      total scores of 3.3 (52%), 1.3 (29%), and 4.6 (42%), respectively, compared with
      decreases of 0.7 (12%), 0.4 (9%), and 1.1 (11%), respectively, in the placebo
      group (P < .05). Peak urine flow increased by a mean of 2.6 mL/s (30%) in
      terazosin-treated patients and 1.2 mL/s (14%) in placebo-treated patients (P < or
      = .05). Adverse events that differed significantly in the two groups were
      dizziness (19% in the terazosin group vs 5% in the placebo group) and urinary
      tract infection (1% in the terazosin group vs 10% in the placebo group).
      CONCLUSIONS: These results suggest that terazosin given once daily in doses up to
      10 mg alleviates symptoms and improves peak urine flow rate in men with benign
      prostatic hyperplasia and has an acceptable adverse event profile.

PMID- 7509244
TI  - Role of neutral endopeptidase and kininase II on substance P-induced increase in
      nasal obstruction in patients with allergic rhinitis.
AB  - We studied the role of neutral endopeptidase (NEP) and kininase II (angiotensin
      converting enzyme; ACE) in the modulation of exogenous substance P (SP)-induced
      nasal response in normal subjects and in patients with allergic rhinitis. We
      measured the nasal conductance in response to increasing doses of SP 2 h after
      oral administration of either placebo or the ACE inhibitor, cilazapril (5 mg), or
      the NEP inhibitor, acetorphan (300 mg), given in a randomized, double-blind,
      cross-over manner. We performed three separate studies: acetorphan versus placebo
      and cilazapril versus placebo, in normal subjects (n = 6 and n = 8,
      respectively), and acetorphan versus cilazapril versus placebo in patients with
      allergic rhinitis (n = 6). In normal as well as in rhinitic subjects, SP
      decreased nasal conductance in a dose-dependent fashion (p < 0.001). With
      placebo, the decrease in nasal conductance in normal subjects was similar to that
      in patients with allergic rhinitis (p > 0.5). In normal subjects, acetorphan
      potentiated the decrease in nasal conductance (p < 0.001), whereas cilazapril did
      not (p = 0.12). In patients with allergic rhinitis, the decrease in nasal
      conductance was potentiated by acetorphan (p < 0.001) and by cilazapril (p <
      0.001). With acetorphan, the decrease in nasal conductance was not different in
      patients with allergic rhinitis and in normal subjects (p > 0.9). Conversely,
      with cilazapril, the nasal response to SP was greater in patients with allergic
      rhinitis than in normal subjects (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509247
TI  - Capsaicin desensitization inhibits swallowing reflex in guinea pigs.
AB  - To determine whether capsaicin-sensitive sensory nerves are involved in the
      swallowing reflex, we examined swallowing reflex in terms of the number of
      swallows elicited by injections of three different volumes (0.2, 0.4, and 0.6 ml)
      of distilled water, into the pharynx through a catheter in anesthetized guinea
      pigs pretreated with and without systemic capsaicin. The number of swallows was
      counted by submental electromyographic activity and visual observation of
      characteristic laryngeal movement. Injections of distilled water caused a volume
      dependent increase in the number of swallows in animals treated with and without
      capsaicin. Capsaicin treatment significantly decreased the number of swallows
      elicited by all volumes of distilled water (p < 0.01). Exogenously administered
      substance P (SP) caused a dose-dependent increase in the number of swallows in
      all volumes but calcitonin gene-related peptide and acetylcholine were without
      effect. FK 888 (10(-5) M; 1 ml), a specific inhibitor of NK1 receptor, reduced
      the number of swallows elicited by distilled water to a similar degree as
      capsaicin treatment. Pharyngeal application of lidocaine (4%; 1 ml) also
      inhibited distilled water-induced swallowing. These results suggest that
      nonmyelinated C-fibers regulate the swallowing reflex through the release of SP
      in response to stimulation.

PMID- 7509245
TI  - Contractile effects of bradykinin on the isolated human small bronchus.
AB  - Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5
      to 1 mm) from 20 patients. pD2 was 7.7 +/- 0.1 (pD2 = -log EC50) and maximal
      effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B2
      agonist [Hyp3TyrMe8]Bk contracted airway smooth muscle with a pD2 of 7.8 +/- 0.2
      and an Emax of 39 +/- 9%. The B1 agonist [Sar1dPhe8desArg9]Bk induced only a weak
      contraction at 10(-6) M. The effect of Bk was abolished by the B2 (Hoe 140) but
      not by the B1 [Leu8desArg9]Bk receptor antagonist. Indomethacin 10(-6) M
      abolished Bk-induced contraction, suggesting that cyclooxygenase products are
      involved in Bk action. Capsaicin 10(-5) M, which selectively depletes C fibers
      from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5)
      M significantly inhibited the concentration-response curves to Bk. However,
      tetrodotoxin (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect
      Bk concentration-response curves, suggesting that nerve conduction, substance P
      (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk
      action. Our data indicate that Bk contracts human distal airway smooth muscle
      through the Bk B2 receptor and a cyclooxygenase pathway. This effect appears to
      involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA
      and SP release.

PMID- 7509249
TI  - Convergent projections of trigeminal afferents from the principal nucleus and
      subnucleus interpolaris upon rat ventral posteromedial thalamic neurons.
AB  - Synaptic boutons originating from the trigeminal principal sensory nucleus (PrV)
      and the subnucleus interpolaris (SpI) which contact rat ventral posteromedial
      (VPM) neurons are similar in appearance. They are large boutons and contain a
      moderate packing density of round synaptic vesicles and established asymmetric
      (Gray type I) synaptic contacts principally on dendrites occasionally on somata.
      These boutons are similar to RL boutons of dorsal column nuclei and spinothalamic
      tract origin found in the ventral posterolateral thalamic nucleus. The boutons of
      PrV and SpI origin have an overlapping distribution on proximal dendrites of VPM
      neurons. Double labeling using degeneration and WGA-HRP shows that boutons from
      PrV and SpI contact the same VPM neurons confirming there is convergence of
      trigeminal afferents in VPM.

PMID- 7509250
TI  - Calcitonin gene-related peptide and substance P immunoreactivity in the monkey
      trigeminal ganglion, an electron microscopic study.
AB  - Calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity was
      examined in neurons of the monkey trigeminal ganglion. Moreover, CGRP- and SP
      positive varicose nerve fibers were found, occasionally forming pericellular
      arborizations around trigeminal somata, which, at light microscopic level,
      suggested the existence of synaptic contacts. Electron microscopic investigation
      however, revealed that although these varicose fibers ran in close range of
      somata and were containing accumulations of CGRP- and SP-positive vesicles,
      classical synaptic contacts were not present.

PMID- 7509246
TI  - Anti-edema action of formoterol in rat trachea does not depend on capsaicin
      sensitive sensory nerves.
AB  - The beta 2-adrenergic agonist formoterol has been shown to inhibit plasma
      extravasation in the respiratory mucosa associated with neurogenic inflammation
      as well as that caused by histamine or bradykinin. It is unknown whether these
      effects of formoterol are mediated through an action of sensory nerves or through
      a direct effect on the leaky blood vessels. In the present study we sought to
      determine whether capsaicin-sensitive sensory nerves are essential for the anti
      edema effect of formoterol in the rat trachea. Substance P (5 micrograms/kg), PAF
      (hexadecyl-PAF, 5 micrograms/kg), or bradykinin (10 mg/kg) was injected
      intravenously to increase vascular permeability. The amount of plasma
      extravasation was measured with two tracers, Evans blue dye and Monastral blue
      pigment. The effectiveness of formoterol's anti-edema action was assessed in two
      groups of rats. One was pretreated with capsaicin to eliminate tachykinin
      containing sensory nerves and another, the control group, was not pretreated. We
      found that in control rats formoterol inhibited to a similar extent the
      extravasation of Evans blue and Monastral blue caused by all three mediators. The
      highest intravenous dose of formoterol (10 micrograms/kg) reduced substance P
      induced extravasation of Monastral blue by 59%, reduced PAF-induced extravasation
      by 74%, and reduced bradykinin-induced extravasation by 58%. Pretreatment of rats
      with a dose of capsaicin that eliminated at least 94% of the substance P
      immunoreactive nerve fibers did not significantly reduce the effectiveness of
      formoterol against any of the mediators.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509248
TI  - Cytokine indices in Alzheimer's temporal cortex: no changes in mature IL-1 beta
      or IL-1RA but increases in the associated acute phase proteins IL-6, alpha 2
      macroglobulin and C-reactive protein.
AB  - Recent immunocytochemical data have demonstrated increases in interleukin-1 beta
      (IL-1 beta), interleukin-6 (IL-6) and the IL-6-inducible acute phase protein,
      alpha 2-macroglobulin (alpha 2-M), in Alzheimer's disease (AD) brains. We
      investigated the levels of these proteins quantitatively using ELISA procedures
      and determined if increases in IL-1 beta were compensated for by a parallel
      increase in the endogenous interleukin-1 receptor antagonist (IL-1RA). Comparing
      control vs. Alzheimer's temporal cortex, we examined mature IL-1 beta, IL-1RA, IL
      6, alpha 2-M and C-reactive protein (CRP). The specificities of the ELISA
      procedures were verified by serial dilutions of the samples; by chromatofocusing,
      and by Sephadex G-150 gel filtration. There were no differences in the levels of
      mature IL-1 beta or IL-1RA in AD and control brains. However, IL-6 levels were
      detectable in 14 of the 16 Alzheimer samples but only 2 of the 14 control
      samples. There were also significant increases seen in alpha 2-M and CRP levels
      in the Alzheimer's group compared to controls. These data support previous
      studies demonstrating a possible up-regulation of neuroimmune function in
      Alzheimer's cortex; however, we cannot determine, at this time, if this immune
      reaction is initiated by IL-1 beta.

PMID- 7509251
TI  - [Further study of tumor markers].

PMID- 7509253
TI  - [Glutathione S-transferases in carcinogenesis and diagnosis of liver cancer].
AB  - We studied the relations between glutathione S-transferases (GSTs) from human
      liver and hepatic cancer and preneoplastic lesions in high risk area of Qidong
      city and Beijing. A biotin-avidin enzyme-linked immunoassay (BA-ELISA) for serum
      level of GSTs was developed. The results showed that the GSTs level of normal
      controls in Qidong city (0.66 +/- 0.54 ng/ml) was higher than that in Beijing
      (0.37 +/- 0.27 ng/ml). The members of high cancer families, HBVsAg carries and
      patients having a low level fluctuating pattern of serum AFP were the population
      with high risk of liver cancer; their serum level of GSTs was 1.25 +/- 1.46, 1.43
      +/- 1.44 and 2.81 +/- 1.76 ng/ml respectively, and it was significantly higher
      than in the normal controls. The content of GSTs of hepatic cancer patients in
      Qidong city and Beijing was 3.03 +/- 3.35 and 3.60 +/- 3.70 ng/ml respectively,
      but the positive rate (97%) of GSTs in Qidong city was higher than that (82%) in
      Beijing. The results suggested that serum expression of GSTs can be used as an
      enzyme marker for hepatic cancer and preneoplastic lesions. Possible roles of
      these forms in hepatic carcinogenesis induced by chemical carcinogenesis were
      discussed.

PMID- 7509252
TI  - [Characterization and detection of cancer-associated antigens in patients with
      gastric cancer].
AB  - Six monoclonal antibodies reacted with different cancer-associated antigens were
      studied. In which, CL-2 reacts with carcinoembryonic antigen (CEA), CL-3: CEA and
      S-Tn, CL-4: glycosphingolipid, PS-7: S-Tn. PS-10: S-Tn Tn, and glycosphingolipid,
      all weakly, and GS-2: CEA, Tn, S-Tn, glycolipid, all strongly. All of the
      monoclonal antibodies expressed strongly in gastric cancer tissues, the positive
      rate are 62%-91.6%, but none are expressed in normal gastric tissues, except PS-7
      (35% weakly expressed). The cancer-associated antigens in gastric juice, serum
      and feces were detected by binding inhibition ELISA and SDS-PAGE; Western blot
      methods. The results showed that: (1) The positive rates in gastric cancer are
      all over 90%, when detected by cock-tail monoclonal antibodies of any three. The
      false positive rates are 8%- 14%. (2) Detection of cancer-associated antigens in
      gastric juice and feces gives higher positive rates than in serum, it shows the
      carbohydrate antigens is relatively more stable than the protein when it passes
      through the gastrointestinal canal. (3) The monoclonal antibodies against S-Tn,
      Tn, and glycosphingolipid antigens are good markers for the diagnosis of gastric
      cancer.

PMID- 7509255
TI  - Adjuvant chemotherapy for stage II nonseminomatous germ cell cancer of the
      testis.
AB  - BACKGROUND: The success of chemotherapy for Stage III testicular carcinoma
      warranted its use as an adjuvant therapy for Stage II cancer. The current report
      reflects the adjuvant program begun at the University of Minnesota using four
      courses of vinblastine, bleomycin, and cisplatin (VBP) before the onset of the
      Testicular Cancer Intergroup Study using two courses of chemotherapies. METHODS:
      A review of 78 patients with Stage II nonseminomatous germ cell tumors treated
      between 1972 and 1986 defined three groups: 19 patients treated between 1972 and
      1979 with various adjuvant chemotherapies (termed "other"), 37 patients treated
      from 1975 to 1986 with VBP adjuvant chemotherapy, and 21 patients who received no
      therapy during the same era of VBP. The latter group was not offered adjuvant
      chemotherapy at other institutions or declined therapy. RESULTS: Nineteen
      patients received adjuvant chemotherapy before the cisplatin era. Their survival
      rate was 42%, including two patients treated with cisplatin-based chemotherapy
      for recurrence. In the group of 21 patients who did not receive adjuvant therapy,
      14 (66.7%) survived. Of these, five had no recurrence and nine were treated for
      recurrence. In a third group, adjuvant VBP therapy was given to 37 patients, 32
      of whom received four full courses. There have been no recurrences, and 36
      (97.3%) remain alive; one obese patient with hypertension died of a ruptured
      aortic aneurysm 12.9 years after the retroperitoneal lymph node dissection. Nodal
      involvement was more extensive in the VBP group. CONCLUSION: Four courses of VBP
      adjuvant chemotherapy for pathologic Stage II testicular cancer resulted in a
      100% cure rate, all patients having been followed up for more than 6 years.
      Whether two courses are as adequate remains to be determined when long-term
      follow-up is reported.

PMID- 7509254
TI  - Primary adenoid cystic carcinoma of the lung. A clinicopathologic and
      immunohistochemical study of 16 cases.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare but distinctive salivary
      gland-type malignant neoplasm that arises infrequently as a primary tumor in the
      lung. METHODS: The clinical and pathologic features in 16 cases of primary ACC of
      the lung were reviewed, and immunohistochemical stains on paraffin sections were
      performed in 7 cases. RESULTS: The patients' ages ranged from 29 to 79 years
      (mean age, 54 years); 11 were men and 5 were women. Clinically, most patients
      were seen initially with obstructive symptoms, including cough, wheezing,
      shortness of breath, and hemoptysis. Eight tumors were in the left lung and eight
      in the right lung. The lesions were treated by pneumonectomy in seven patients,
      lobectomy in six, and lobectomy plus chemotherapy in two. One patient was treated
      with chemotherapy alone after undergoing a diagnostic biopsy that revealed
      advanced disease. Grossly, most lesions were described as endobronchial and
      measured from 0.9 to 4.0 cm in greatest dimension; two cases, however, showed
      poorly circumscribed infiltrative tumors. Histologically, three main growth
      patterns were identified admixed in various proportions: cribriform
      (cylindromatous), tubular, and solid. Immunohistochemical study in six of seven
      cases showed a prominent myoepithelial cell component, as evidenced by
      immunoreactivity for keratin, actin, and S-100 protein in numerous tumor cells.
      Clinical follow-up ranging from 2 to 15 years in six patients showed that three
      were alive and well without evidence of recurrence or metastases at 5, 10, and 12
      years, respectively, and three were alive with recurrence at 2, 5, and 15 years,
      respectively. Three other patients died of unrelated conditions at 2, 7, and 9
      years, respectively, after diagnosis. Two patients in the study were seen
      initially with metastatic spread at the time of initial diagnosis and died 2
      months and 1 year later with widespread metastases to lymph nodes, liver, spleen,
      kidney, and bone despite intensive chemotherapy. CONCLUSIONS: Disease stage at
      the time of diagnosis may play an important role in predicting the clinical
      outcome of patients with these tumors. Despite their generally slow and indolent
      growth in other locations, ACC arising in the lung may in certain cases be more
      aggressive.

PMID- 7509256
TI  - Analysis of the low affinity high capacity estrogenic binding in human benign
      prostatic hypertrophy.
AB  - The binding of estradiol in extracts of human benign prostatic hypertrophy (BPH)
      tissue was studied using the agar gel electrophoretic method. Two distinct
      binding peaks were observed having the same high specificity for natural
      estrogens and very poor affinity for the other classes of steroids as well as for
      diethylstilbestrol (DES). Therefore, it is highly probable that these peaks are
      two different forms of the low affinity binding protein present in human
      prostate. Cytosols were shown to contain smaller amounts of the binding proteins
      than the tissular extracts. This difference probably resulted from protein
      degradation occurring during the time required to prepare the cytosol. The
      concentrations of the extract and of the radiolabeled ligand, the composition of
      the buffer, the addition of sodium molybdate, sodium tartrate or proteolytic
      inhibitors, were evaluated in order to delineate optimal binding conditions. The
      possible function of these low-affinity high-capacity binding proteins is
      discussed.

PMID- 7509257
TI  - Antiplatelet efficacy and specificity of DMP728, a novel platelet GPIIb/IIIa
      receptor antagonist.
AB  - The present study was undertaken to define the platelet GPIIb/IIIa affinity and
      specificity of DMP728, the cyclic [(D-2-aminobutyrate-N-methyl-L-arginyl-glycyl-L
      aspartyl)-3-aminomethyl- benzoic acid] methane sulfonate. DMP728 demonstrated
      similar potency (IC50 = 0.046 +/- 0.002 microM) in inhibiting human platelet
      aggregation induced by various agonists or combination of agonists as assessed
      either by light transmittance aggregometry or impedance techniques. Similarly,
      DMP728 inhibited (IC50 = 2.3 +/- 0.8 nM) with equipotency in inhibiting 125I
      fibrinogen binding to human gel-purified platelets regardless of the agonist
      used. In purified human GPIIb/IIIa ELISA, DMP728 demonstrated a competitive high
      affinity binding (Ki = 0.4 nM). Additionally, a high binding affinity (Kd = 0.1
      nM) of 3H-DMP728 was demonstrated in human platelets. Furthermore, a platelet
      deaggregatory efficacy was shown. DMP728 demonstrated a high degree of
      specificity for platelet GPIIb/IIIa (alpha 2/beta 3) as compared to other
      integrins on endothelial cells (vitronectin receptors), platelets GPIb/1X, alpha
      v/beta 3, and other integrins on leukocytes or nonintegrin-related systems. In
      conclusion, DMP728 is a novel antiplatelet agent with high affinity and
      specificity for platelet GPIIb/IIIa.

PMID- 7509258
TI  - Palmitoyl-L-carnitine modifies the function of vascular endothelium.
AB  - OBJECTIVE: Palmitoyl-L-carnitine, which accumulates in ischaemic myocardium, may
      influence the function of vascular endothelium in the ischaemic area. The aim of
      the study was therefore to examine the effect of palmitoyl-L-carnitine on
      endothelium dependent relaxations of rabbit thoracic aortas and its effects on
      the intracellular calcium regulation in cultured bovine aortic endothelial cells
      (BAEC). METHODS: Isometric contraction experiments on rabbit thoracic aorta were
      performed to evaluate the effect of palmitoyl-L-carnitine on endothelium
      dependent relaxation. BAEC were isolated by scraping the internal surface of the
      aorta from slaughtered cow, and were cultured in Dulbecco's modified Eagle's
      medium supplemented with fetal calf serum (15% v/v). Cultures used in the present
      study were from the third to the 12th passage. The cytosolic Ca2+ level in BAEC
      was monitored by the fura-2 method. RESULTS: Palmitoyl-L-carnitine (1-20 microM)
      inhibited endothelium dependent relaxation induced by acetylcholine and substance
      P in a dose dependent manner, while having no effect on resting tension and
      glyceryl trinitrate induced relaxations. Bradykinin, another endothelium
      dependent relaxant, induced a biphasic Ca2+ transient in BAEC. Pretreatment of
      BAEC with palmitoyl-L-carnitine (5-10 microM) inhibited bradykinin induced Ca2+
      transients. CONCLUSIONS: The inhibitory effect of palmitoyl-L-carnitine on
      endothelium dependent relaxation results from the suppression of the
      intracellular calcium signal transduction in endothelial cells. We speculate that
      palmitoyl-L-carnitine may be an important mediator of the impaired vascular
      endothelial function in myocardial ischaemia.

PMID- 7509259
TI  - Effects of a nitric oxide synthase inhibitor in humans with septic shock.
AB  - OBJECTIVE: Studies in animals have indicated that increased production of nitric
      oxide from an inducible isoform of nitric oxide synthase contributes to the
      pathophysiology of endotoxic and cytokine induced shock. The aim of this study
      was to determine the role of nitric oxide in septic shock in humans. METHODS: The
      study was a randomised, double blind, placebo controlled investigation of the
      effects of the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA)
      in 12 patients with severe sepsis associated with hypotension. Measurements of
      haemodynamic, haematological, and biochemical variables were made. RESULTS: L
      NMMA (0.3 and 1 mg.kg-1) produced a dose dependent increase in mean arterial
      pressure, systemic vascular resistance, pulmonary vascular resistance, central
      venous pressure, and pulmonary artery occlusion pressure, and a decrease in
      cardiac output and heart rate. In response to the highest dose of L-NMMA systemic
      vascular resistance increased from 547(SEM 92) to 889(143) dyne.s.cm-5, mean
      arterial blood pressure increased from 80.9(2.9) to 100.5(6.1) mm Hg, and cardiac
      output decreased from 11.2(2.1) to 8.9(1.9) litres.min-1. Continuous infusion of
      L-NMMA (1 mg.kg-1 x h-1) produced sustained haemodynamic changes. Platelet
      numbers decreased during the course of the study in both the L-NMMA and the
      placebo group and did not differ significantly between the groups. CONCLUSIONS:
      Low doses of L-NMMA cause a widespread increase in vascular tone and raise blood
      pressure in patients with septic shock. Overproduction of nitric oxide appears to
      be an important mechanism in septic shock in patients, and inhibition of nitric
      oxide synthesis might provide a novel therapeutic approach to this condition.
      However, L-NMMA produced a fall in cardiac output and it is possible that this
      would worsen tissue perfusion. Larger studies examining the effects of L-NMMA on
      mortality and morbidity are now required.

PMID- 7509260
TI  - Preconditioning of isolated rabbit cardiomyocytes: induction by metabolic stress
      and blockade by the adenosine antagonist SPT and calphostin C, a protein kinase C
      inhibitor.
AB  - OBJECTIVE: The aim was to determine if isolated rabbit cardiomyocytes could be
      preconditioned. METHODS: Cardiomyocytes isolated from rabbit hearts were
      subjected to 15 min oxygenated preincubation, with and without substrate, prior
      to concentration into an ischaemic slurry, with or without glucose present. The
      effects of an adenosine agonist (CCPA), an adenosine receptor blocker (SPT), and
      the protein kinase C blocker, calphostin C, on rates of ischaemic contracture and
      survival of the myocytes were determined after various times of ischaemia,
      following resuspension of the cells in hypotonic media. RESULTS: A glucose-free
      preincubation period protected myocytes from subsequent ischaemic injury, with a
      40% reduction of cell death at 90-120 min and 1-2 h delay in cell death. CCPA
      added during preincubation and during the ischaemic period also tended to protect
      from injury, but the differences were not significant and protection was less
      than with a glucose-free preincubation. Although preincubation with CCPA did not
      precondition, SPT added to the preincubation medium only, or to both the
      preincubation medium and the ischaemic pellet, inhibited the preconditioning
      effect of a glucose-free preincubation period. Calphostin C, added only into the
      ischaemic pellet, inhibited the preconditioning effect of glucose-free
      preincubation. CONCLUSIONS: Glucose-free preincubation protects ischaemic
      isolated myocytes from subsequent ischaemia. The degree of protection is great
      enough to account for protection seen in intact hearts, following preconditioning
      protocols. Protection is blocked by SPT and a highly specific protein kinase C
      inhibitor, calphostin C. Protection from ischaemic injury that seems to mimic
      ischaemic preconditioning can be induced in isolated cardiomyocytes, and appears
      dependent on adenosine receptors and activation of protein kinase C.

PMID- 7509265
TI  - Aprotinin therapy to reduce blood loss in Jehovah's Witnesses.

PMID- 7509266
TI  - Sensitive chemiluminescent immunoassay for human granulocyte colony-stimulating
      factor (G-CSF) in clinical applications.

PMID- 7509267
TI  - Detection and identification of Mycobacterium directly from BACTEC bottles by
      using a DNA-rRNA probe.
AB  - Detection and identification of mycobacterial species using DNA-rRNA probes from
      colonies has been used for some time. Guidelines for probe use with a specific
      minimum growth index (GI) cutoff from BACTEC 12B bottles or its use with 7H9
      broth has not been defined. This study defined this minimum GI guideline.
      Clinical specimens received during the study period were decontaminated and
      directly inoculated into BACTEC 12B bottles and appropriate solid media. An
      initial probe test was performed at a GI reading of > or = 100. An additional
      probe test was made at GI of > or = 300. A total of 1377 specimens were processed
      with 98 specimens containing 99 isolates of Mycobacterium. Of these, 82 were M.
      avium complex (MAC), six were M. tuberculosis (Mtb), and 11 were other species.
      At a GI of > or = 100, 82% of MAC were detected; at a GI of > or = 300, 89% were
      detected. All Mtb were detected at a GI of > or = 100. The probes correctly
      identified all isolates from backup 7H9 broths. There were no false-positive
      probe results for any of the isolates from either BACTEC 12B or 7H9 media.
      Therefore, the DNA-rRNA probe test at a GI of > or = 300 saves considerable time
      (on average, 21 days saved) for the detection and identification of Mtb and MAC.
      This time saving compares with waiting for the production of colonies while
      retaining acceptable sensitivity and excellent specificity.

PMID- 7509261
TI  - Combined extracts of Urtica dioica and Pygeum africanum in the treatment of
      benign prostatic hyperplasia: double-blind comparison of two doses.
AB  - The 134 patients (aged 53 to 84 years) with symptoms of benign prostatic
      hyperplasia were drawn from two medical centers in Warsaw. The patients were
      randomly assigned to receive two capsules of the standard dose of an
      urtica/pygeum preparation (300 mg of Urtica dioica root extract combined with 25
      mg of Pygeum africanum bark extract) or two capsules containing half the standard
      dose twice daily for 8 weeks. After 28 days' treatment, urine flow, residual
      urine, and nycturia were significantly reduced in both treatment groups. After 56
      days' treatment, further significant decreases were found in residual urine (half
      dose group) and in nycturia (both groups). There were no between-group
      differences in these measures of efficacy. Five patients reported adverse effects
      of treatment; treatment was not discontinued in any patient because of side
      effects. It is concluded that half doses of the urtica/pygeum extract are as safe
      and effective as the recommended full doses.

PMID- 7509262
TI  - Nitric oxide synthase immunoreactivity in the enteric nervous system of the
      developing human digestive tract.
AB  - We have investigated indirectly the presence of nitric oxide in the enteric
      nervous system of the digestive tract of human fetuses and newborns by nitric
      oxide synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide
      phosphate diaphorase (NADPHd) histochemistry. In the stomach, NOS immunoactivity
      was confined to the myenteric plexus and nerve fibres in the outer smooth
      musculature; few immunoreactive nerve cell bodies were found in ganglia of the
      outer submucous plexus. In the pyloric region, a few nitrergic perikarya were
      seen in the inner submucous plexus and some immunoreactive fibers were found in
      the muscularis mucosae. In the small intestine, nitrergic neurons clustered just
      underneath or above the topographical plane formed by the primary nerve strands
      of the myenteric plexus up to the 26th week of gestation, after which stage, they
      occurred throughout the ganglia. Many of their processes contributed to the dense
      fine-meshed tertiary nerve network of the myenteric plexus and the circular
      smooth muscle layer. NOS-immunoreactive fibres directed to the circular smooth
      muscle layer originated from a few NOS-containing perikarya located in the outer
      submucous plexus. In the colon, caecum and rectum, labelled nerve cells and
      fibres were numerous in the myenteric plexus; they were also found in the outer
      submucous plexus. The circular muscle layer had a much denser NOS-immunoreactive
      innervation than the longitudinally oriented taenia. The marked morphological
      differences observed between nitrergic neurons within the developing human
      gastrointestinal tract, together with the typical innervation pattern in the
      ganglionic and aganglionic nerve networks, support the existence of distinct
      subpopulations of NOS-containing enterice neurons acting as interneurons or
      (inhibitory) motor neurons.

PMID- 7509263
TI  - Nitric oxide synthase-containing nerve fibers and neurons in the genital tract of
      the female mouse.
AB  - Nitric oxide (NO) is generated intracellularly from L-arginine by the action of
      the enzyme nitric oxide synthase (NOS). The present investigation demonstrates
      immunoreactivity against NOS and nicotinamide adenine dinucleotide phosphate
      (NADPH)-diaphorase activity in nerve cells and fibers of the reproductive system
      of the female mouse. The density of nerve fibers staining for NOS varied among
      different genital organs. The ovary and Fallopian tube were devoid of NOS
      positive nerves. The uterine horns received sparse innervation by NOS-containing
      nerve fibers. The most abundant NOergic innervation was found in the uterine
      cervix and vagina, where the nerve fibers ran parallel to the smooth muscle
      bundles and beneath the epithelium; they also accompanied intramural blood
      vessels. The vaginal muscular wall contained single or groups of NOS-reactive
      nerve cells. Clusters of NOS-containing neurons were located in Frankenhauser's
      ganglion at the cervico-vaginal junction. NO may therefore act as a transmitter
      in the nervous control of the female reproductive tract.

PMID- 7509264
TI  - Factors altering DNA synthesis in the cardiac myocyte of the adult newt,
      Notophthalmus viridescens.
AB  - To better understand the mechanisms governing the proliferation of cardiac
      myocytes it is important to identify the factors controlling this phenomenon, and
      to characterize their actions. DNA synthesis was quantified in vitro in
      ventricular myocytes from the adult red-spotted newt, Notophthalmus viridescens.
      Ventricles were enzymatically separated and plated onto laminin. Myocytes were
      fed modified L-15 medium with 10% fetal bovine serum, and were variously treated
      with transforming growth factor-beta, transforming growth factor-beta combined
      with platelet-derived growth factor, acidic fibroblast growth factor, basic
      fibroblast growth factor, 12-0-tetradecanoylphorbol-13-acetate, heparin, or
      conditioned medium from ventricular myocytes or non-myocytes (primarily
      endothelial cells). With their final feeding the cells were given 1 mu Ci/ml of
      tritiated thymidine, and 24 hours later were fixed and stained. Dishes were
      coated with photographic emulsion, exposed, and developed. The percent of cells
      with labeled nuclei was determined. Experimental media that significantly
      increased DNA synthesis included those containing acidic fibroblast growth factor
      (121% of control), basic fibroblast growth factor (119% of control), 12-0
      tetradecanoylphorbol-13-acetate (233% of control) and conditioned medium from
      ventricular myocytes (230% of control) or non-myocytes (128% of control). Media
      significantly inhibiting DNA synthesis were those containing heparin (31% of
      control), transforming growth factor-beta (38% of control), non-myocyte
      conditioned medium and heparin (75% of control), or transforming growth factor
      beta and platelet-derived growth factor (63% of control).

PMID- 7509268
TI  - [Shape memory alloy spiral for urethrostenosis caused by benign prostatic
      hyperplasia].
AB  - The nitinol (shape memory alloy, SMA) spiral was used in 39 patients with benign
      prostatic hyperplasia (BPH). Caine experiment indicated that the spiral could be
      embedded by prostatic urethra epithelium in 6 months. The new transitional
      epithelium between spiral wires was originated from the urethra transitional
      epithelium as proved by immunohistochemical staining. The parts of spiral project
      over the bladder cavity formed incrustation on the spiral tip. The nitinol is of
      super-elastic property, corrosive-resistance and excellent biocompatibility, in
      addition to unique shape memory effect. We treated 39 patients with BPH by self
      made coaxial sheath introducing Chinese nitinol spiral into the prostatic
      urethra, with a successful rate of 89.7%. Follow-up for 3-26 months showed no
      incrustation and migration of the spiral.

PMID- 7509269
TI  - Cortical and thalamic cellular correlates of electroencephalographic burst
      suppression.
AB  - This experimental study on anesthetized cats used intracellular recordings of
      cortical, thalamocortical and reticular thalamic neurons (n = 54), as well as
      multi-site extracellular recordings (n = 36), to investigate the cellular
      correlates of EEG burst-suppression patterns, defined as alternating wave bursts
      and periods of electrical silence. Burst-suppression was elicited by the
      administration of the same or other anesthetic agents upon the background of an
      already synchronized EEG activity. About 95% of cortical cells entered burst
      suppression, in close time-relation with EEG activity, displaying sequences of
      phasic depolarizing events associated with bursts of EEG waves and an electrical
      silence of the neuronal membrane during flat EEG epochs. The membrane potential
      (Vm) hyperpolarized by approximately 10 mV prior to any EEG change and the slow
      rhythms reflecting deep stages of anesthesia progressively disorganized with
      transition to burst-suppression. During flat EEG epochs, the apparent input
      resistance (tested through short hyperpolarizing current pulses) decreased (range
      12-60%) and neuronal responsiveness to orthodromic volleys (tested by thalamic
      and cortical evoked excitatory postsynaptic potentials) was dramatically reduced.
      It is proposed that the decreased input resistance is mainly due to an increase
      in K+ conductances. At variance with cortical neurons, only 60-70% of thalamic
      cells ceased firing before overt EEG burst-suppression and were completely silent
      during flat periods of EEG activity. The remaining 30-40% of thalamic cells
      discharged rhythmic (1-4 Hz) spike bursts during periods of EEG silence. This
      rhythm, within the frequency range of delta waves, is generated in thalamic cells
      by the interplay between two of their intrinsic currents at critical levels of Vm
      hyperpolarization. However, with the deepening of burst-suppression, when silent
      EEG periods became longer than 30 sec, thalamic cells also ceased firing. The
      assumption that full-blown burst-suppression is achieved through virtually
      complete disconnection in brain circuits implicated in the genesis of the EEG is
      corroborated by the revival of normal cellular and EEG activities after volleys
      setting into action thalamic and cortical networks.

PMID- 7509270
TI  - Type III intermittency: a nonlinear dynamic model of EEG burst suppression.
AB  - Burst suppression electroencephalograms from 9 comatose patients have been
      studied using nonlinear dynamic techniques. These EEG records show many dynamical
      features characteristic of nonlinear systems, including sensitive dependence on
      initial conditions, self-organization, similarity across scales, and
      intermittency. Histograms of burst durations showed an asymmetric distribution
      with a decreasing tail of increasing duration. Interpreting the histograms from
      the standpoint of intermittency classifications of iterated dynamical maps, the
      absence of any conspicuous maximal cut-off duration suggests a type III
      intermittency. The power-law exponent of the decreasing tail is -3/2 for type III
      intermittency in the large scale sample size limit, and we have found the EEGs to
      be consistent with type III intermittency behavior. We have also developed a
      nonlinear algorithm which models burst suppression pattern based on a low
      dimensional return map. Burst suppression pattern appears to be the constrained
      activity of a nonlinear dynamical system at the transition to chaos.

PMID- 7509272
TI  - Central mid-temporal spikes triggered by blinking.
AB  - The closed-circuit TV-electroencephalogram (CCTV-EEG) of a 6-year-old boy
      revealed central mid-temporal spikes (CMTS) triggered by blinking. The spikes
      occurred spontaneously, as well as reflexly, following the blinks by 100-200
      msec. Triggered spikes occurred in the light and dark and also while awake and
      drowsy. However, spontaneous spikes, not triggered by blinks, also occurred in
      drowsiness. These findings demonstrate activation of CMTS by an endogenous
      behavior (blinking).

PMID- 7509271
TI  - Circadian rhythms in narcolepsy: studies on a 90 minute day.
AB  - Following a baseline night recording, 8 narcoleptic subjects and 8 sex- and age
      matched controls were maintained on a 90 min sleep/wake schedule for 48-72 h.
      Each cycle consisted of 60 min of enforced wakefulness out of bed, followed by a
      30 min "nap" period in which subjects were asked to try and fall asleep. Upon
      completion of the 90 min sleep/wake protocol, subjects were permitted to sleep ad
      libitum for 24 h. All sleep periods were monitored polygraphically; in addition,
      tympanic temperature and subjective sleepiness were recorded during the 90 min
      sleep/wake schedule. Narcoleptics and controls differed dramatically in their
      sleep patterns during the 90 min sleep/wake schedule. On average, narcoleptics
      obtained 2 more hours per day of total sleep time (TST) than did the controls,
      with REM sleep comprising nearly 2/3 of the incremental sleep time. The two
      groups did not differ with respect to the amount of slow wave sleep (stage 3 + 4;
      SWS). The sleep latency rhythms observed in control subjects were markedly
      diminished in narcoleptics; narcoleptic subjects remained objectively sleepy
      (i.e., had low sleep latencies) even at times corresponding to maximum alertness
      in the control subjects. Rhythms in subjective sleepiness and core temperature
      were, however, robust in both groups. Although TST in narcoleptics exceeded that
      of controls during the 90 min sleep/wake schedule, narcoleptics did not obtain
      more sleep than controls during the baseline or recovery periods. These findings
      suggest that the homeostatic process of sleep regulation is intact in
      narcoleptics. Moreover, it appears that the circadian clock itself is functioning
      normally in narcoleptics. An attenuated clock effector mechanism responsible for
      promoting alertness may, however, explain excessive daytime sleepiness in
      narcoleptics.

PMID- 7509273
TI  - A theoretical and experimental study of high resolution EEG based on surface
      Laplacians and cortical imaging.
AB  - Two different methods to improve the spatial resolution of EEG are discussed: the
      surface Laplacian (e.g., current source density) and cortical imaging (e.g.,
      spatial deconvolution). The former methods tend to be independent of head volume
      conductor model, whereas the latter methods are more model-dependent. Computer
      simulation of scalp potentials due to either a few isolated sources or 4200
      distributed cortical sources and studies of actual EEG data both indicate that
      the two methods provide similar estimates of cortical potential distribution.
      Typical correlation coefficients between either spline-Laplacian or cortical
      image and simulated (calculated) cortical potential are in the 0.8-0.95 range,
      depending partly on CSF thickness. By contrast, correlation coefficients between
      simulated scalp and cortical potential are in the 0.4-0.5 range, suggesting that
      high resolution methods provide much better estimates of cortical potential than
      is obtained with conventional EEG. The two methods are also applied to steady
      state visually evoked potentials and spontaneous EEG. Correlation coefficients
      obtained from real EEG data are in the same general ranges as correlations
      obtained from simulations. The new high resolution methods can provide a dramatic
      increase in the information content of EEG and appear to have widespread
      application in both clinical and cognitive studies.

PMID- 7509274
TI  - A fast method for forward computation of multiple-shell spherical head models.
AB  - Using a combination of 3 suitably located dipoles in a homogeneous sphere, the
      scalp potential due to a dipole source in a 4-shell spherical head model can be
      approximated with a high degree of precision and a more than 30-fold increase in
      computing speed. Magnitudes and locations of the 3 equivalent dipoles can be
      fitted in a homogeneous sphere to data generated from a source at one location in
      a 4-shell head model. The resulting parameters are used to compute scalp
      potentials for sources at other locations and orientations. Residual variance
      measures showed close agreement between the new approximation and a standard 4
      shell computation method. Further tests of the method used scalp data from 500
      randomly selected pairs of sources generated by the standard 4-shell computation
      and fitted using, for forward computations, the new approximation and the single
      shell Ary-corrected head model. Errors with the new approximation were marginally
      larger than with the standard computation, but sources were located within 0.5 mm
      and 0.6 degrees of the original position in 99% of the fits. 99% error limits for
      the Ary model were up to 18 mm and 25 degrees and depended on the head model
      parameters.

PMID- 7509275
TI  - The topography of visual evoked response properties across the visual field.
AB  - Visual evoked potentials (VEPs) to luminance and pattern reversal stimulation
      were derived for a large number of small areas throughout the central visual
      field. In one study, the field was tested with a stimulus array consisting of 64
      equal-area patches. Local response components were extracted by independent m
      sequence modulation of the patches. Field topographies were compared between and
      within subjects using different electrode placements. The subject-dependent local
      variability observed in response characteristics is attributed to contributions
      from two or more cortical representations of the visual field and to inter
      subject variations in gross cortical anatomy. The second study used luminance
      modulation of 56 patches across a 15 degrees field, scaled to activate
      approximately equal cortical areas in area V1. This produced many robust signals
      at all eccentricities. Bipolar and double differential ("1-dimensional
      Laplacian") signals were compared. The double differencing reduced contributions
      from distant or distributed sources, enhancing nearby current source activity,
      and greatly improved S/N for many stimulus locations. The high-resolution visual
      field maps demonstrated that clinical field testing using the VEP is not feasible
      because of effects of cortical convolutions on responses. However, the vast
      improvement in data quality and quantity make it a useful tool for VEP source
      localization and identification.

PMID- 7509276
TI  - The auditory evoked sustained field: origin and frequency dependence.
AB  - A sound lasting for several seconds is known to elicit a baseline shift in
      electrical and magnetic records. We have studied the dependence of the magnetic
      field distribution of this "per-stimulatory" sustained field (SF) on tone
      frequency. Tone bursts of 2 sec duration and 60 dB nHL intensity were presented
      to 11 subjects at varying interstimulus intervals between 5 and 7 sec. The
      carrier frequencies of 250, 1000 and 4000 Hz varied randomly from trial to trial.
      The field distributions obtained are consistent with the view that the auditory
      evoked sustained field activity originates in the supratemporal cortex.
      Differences in the locations of equivalent current dipoles of the SF from those
      of the M100 wave of the slow auditory evoked field are consistent across
      subjects. The SF source locations corresponding to stimulus frequencies over an
      extended frequency range are arranged in a tonotopic manner and support the idea
      that the sources of the M100 and the SF are current dipole sheets located on the
      superior surface of the primary auditory cortex.

PMID- 7509277
TI  - Blood lead levels of British competitive cyclists.
AB  - This study examined the extent to which the potentially toxic lead particulates
      emitted from motor vehicles are absorbed by competitive cyclists. A time trial (n
      = 5), a road race (n = 5), and a sedentary control group (n = 5) were examined
      with respect to blood lead (PbB) levels. In the two cycling groups, the PbB
      levels were measured before and after (1) a time trial (80 km) held on a dual
      carriageway; and (2) a road race (120 km) which took place in a rural area. Mean
      (+/- SE) resting PbB levels for the sedentary subjects, time trialists, and road
      racers were 0.442 +/- 0.041, 0.490 +/- 0.111 and 0.384 +/- 0.061 mumol l-1
      respectively (p > 0.05). Mean post-race PbB levels of the time trialists (0.528
      +/- 0.046 mumol l-1) and road racers (0.346 +/- 0.024 mumol l-1) did not differ
      significantly from the pre-race levels (p > 0.05). However, after their
      respective races, the mean PbB level of the time trialists was higher than that
      of the road racers (p < 0.05). Ninety minutes of cycling (70% VO2 max) in a
      laboratory containing approximately 1 microgram m3 of airborne lead did not
      affect blood lead levels. All PbB levels compiled with EC regulations regarding
      lead exposure. Despite a positive relationship between the amount of training and
      the PbB levels (r = 0.64, p < 0.05), competitive cyclists did not evidence
      abnormal levels of lead absorption. Time trialing on dual carriageways was
      associated with higher PbB levels than road racing.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7509278
TI  - Specific CD45 isoforms differentially regulate T cell receptor signaling.
AB  - Multiple isoforms of T cell CD45 tyrosine phosphatase are expressed as a result
      of alternative RNA splicing among extracellular exons. To discern the presence
      and identity of distinct functions among CD45 isoforms, we compared thymic T cell
      activation responses by elevating expression of two CD45 isoforms normally found
      on quiescent T cells. We report that CD45RABC significantly increased CD4+ thymic
      T cell proliferation in both a mixed lymphocyte reaction and following anti-T
      cell receptor (TCR) antibody stimulation. Additionally, CD45RABC enhanced Ca2+
      mobilization and phosphotyrosine accumulation, and suppressed the inhibitory
      effect of anti-CD4 antibodies. By contrast, CD45R0 did not enhance TCR signaling
      or phosphotyrosine levels in CD4+ thymic T cells and required a TCR co-stimulus
      to augment cellular proliferation. These studies provide genetic evidence that
      alternative CD45 isoforms are functionally distinct and disclose a unique
      mechanism by which T cell immunologic responsiveness can be modified.

PMID- 7509280
TI  - Transactivation of the minus-strand DNA transfer by nucleocapsid protein during
      reverse transcription of the retroviral genome.
AB  - Two DNA strand transfers are required during reverse transcription of the RNA
      genome of retroviruses to complete provirus synthesis. To understand more about
      the first strand transfer reaction, that of the minus-strand DNA from the 5' to
      the 3' end of the retroviral genome, we devised an in vitro system mimicking the
      Moloney murine leukemia virus reverse transcription process. Two RNAs
      corresponding to the 5' and 3' regions of the genome were used to perform reverse
      transcription assays. The role of the nucleocapsid protein NCp10, which is
      tightly bound to the genome in the virus, was investigated in this system as well
      as the requirement of the 5' and 3' terminal repeats (R sequences) and the
      poly(A) tail. The results show that NCp10 drastically enhances the strand
      transfer reaction and that interactions between reverse transcriptase,
      nucleocapsid protein and viral RNA may be important. Both R sequences are
      required for an efficient and accurate DNA strand transfer and the poly(A) tail
      facilitates this reaction. Furthermore, it is probable that both intra- and
      intermolecular DNA strand transfers occur when the 5' and 3' ends of the genome
      are present on the same molecule.

PMID- 7509279
TI  - Dissociation of TNF-alpha cytotoxic and proinflammatory activities by p55
      receptor- and p75 receptor-selective TNF-alpha mutants.
AB  - Human tumour necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine capable
      of killing mammalian tumour cells in vitro and in vivo, and of enhancing the
      proinflammatory activity of leucocytes and endothelium, the latter effects
      limiting its usage as an antitumour agent in humans. Using TNF-alpha mutants with
      a selective capacity to bind to the TNF p55 receptor (TNFR55) or to the p75
      receptor (TNFR75) we show here that these two major activities of TNF-alpha can
      be dissociated. The TNFR55-selective mutants (R32W, E146K and R32W-S86T) which
      bind poorly to TNFR75 displayed similar potency to wild-type TNF in causing
      cytotoxicity of a human laryngeal carcinoma-derived cell line (HEp-2) and
      cytostasis in a human leukaemic cell line (U937). However, these TNFR55-selective
      mutants exhibited lower proinflammatory activity than wild-type TNF.
      Specifically, TNF-alpha's priming of human neutrophils for superoxide production
      and antibody-dependent cell-mediated cytotoxicity, platelet-activating factor
      synthesis and adhesion to endothelium were reduced by up to 170-fold. Activation
      of human endothelial cell functions represented by human umbilical venular
      endothelial cell (HUVEC) adhesiveness for neutrophils, E-selectin expression,
      neutrophil transmigration and IL-8 secretion were also reduced by up to 280-fold.
      On the other hand, D143F, a TNFR75-selective mutant tested either alone or in
      combination with TNFR55-selective mutants, did not stimulate these activities
      despite being able to cause cytokine production in TNFR75-transfected PC60
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509281
TI  - The catalytic properties of the reverse transcriptase of the lentivirus equine
      infectious anemia virus.
AB  - The reverse transcriptase (RT) of equine infectious anemia virus (EIAV) shares
      sequence similarity with the RTs of other lentiviruses, particularly with the RTs
      of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2, respectively),
      the causative agents of acquired immunodeficiency syndrome (AIDS). There is a 41
      42% sequence identity between EIAV RT and both HIV RTs (which have 61% sequence
      identity to each other). We have compared the enzymic properties of EIAV RT with
      those of HIV-1 RT. Several aspects of the activities of EIAV RT differ from the
      corresponding activities of HIV-1 RT. There are significant differences in the
      inhibition of the DNA polymerase activities by the deoxynucleoside triphosphate
      analogs, 3'-azido-2,3'-dideoxythymidine triphosphate, dideoxyTTP and dideoxyGTP
      and by the nonnucleoside inhibitor, tetrahydroimidazo[4,5,1-jk-1,4]benzodiazepin
      2-(1H)-one and thione; in the dependence of DNA polymerase and RNase H activities
      on pH; in the inhibition of the DNA polymerase activities by the thiol-specific
      reagent N-ethylmaleimide; in the specific DNA polymerase activity; in the
      inhibition of the ribonuclease H activity by the zinc chelator
      orthophenanthroline. However, there are several cases in which EIAV RT and HIV-1
      RT are more similar than was previously found for HIV-1 RT and HIV-2 RT. These
      include the Km values for the DNA polymerase activities, the heat stability of
      the DNA polymerase functions and the specific activity of the RNase H function.

PMID- 7509282
TI  - Hepatitis C virus infection among sexually promiscuous groups and the
      heterosexual partners of hepatitis C virus infected index cases.
AB  - To define the role of sexual transmission in the spread of hepatitis C virus
      (HCV) infection, a seroprevalence study of antibodies against HCV was performed
      in populations at high risk for sexually transmitted diseases. Subjects included
      310 female prostitutes, 88 clients of prostitutes, 168 homosexual men and 147
      stable heterosexual partners of index cases reactive for anti-HCV (98 of whom
      were partners of drug addicts coinfected with HCV and human immunodeficiency
      virus [HIV]). All subjects denied prior transfusion or intravenous drug use.
      Controls were 400 voluntary blood donors selected randomly from first-time
      donors. The prevalence of anti-HCV by enzyme immunoassay, confirmed by a second
      generation recombinant immunoblot assay, was 6.4% in prostitutes, 6.8% in clients
      of prostitutes, 4.2% in homosexual men, 7.4% in heterosexual partners of index
      cases and 1.2% in random donors. However, the anti-HCV prevalence in stable
      heterosexual partners of HCV-positive/HIV-positive index cases was 2.2 times
      higher than in stable heterosexual partners of index cases reactive for anti-HCV
      only (9.2% vs. 4.1%), and sexual partners of index cases coinfected with HCV and
      HIV were almost three times more likely to be infected with HIV than with HCV
      (25.5% vs. 9.2%). These data suggest that HCV infection may be sexually
      transmitted but with low efficiency and that this efficiency could be increased
      in the presence of coexistent HIV infection in the index case.

PMID- 7509283
TI  - Inhibition of neuronal nicotinic acetylcholine receptors by imipramine and
      desipramine.
AB  - The actions of two structurally related tricyclic antidepressants on neuronal
      nicotinic acetylcholine receptors were investigated in human neuroblastoma (SY
      SY5Y) cells, using whole-cell patch-clamp recordings. Both desipramine and
      imipramine reversibly inhibited inward currents evoked by application of the
      nicotinic receptor agonist dimethylphenylpiperazinium iodide (30-300 microM) with
      IC50 values of 0.17 microM and 1.0 microM respectively (holding potential -70
      mV). The degree of current inhibition caused by either tricyclic compound was
      unaffected by agonist concentration (30-300 microM). The effects of desipramine
      were voltage-independent over the range -40 mV to -100 mV, and inhibition caused
      by imipramine only increased very slightly with membrane hyperpolarization over
      the same range. These results indicate that tricyclic antidepressants can inhibit
      neuronal nicotinic acetylcholine receptors by mechanisms which are distinct from
      their actions at non-neuronal nicotinic acetylcholine receptors.

PMID- 7509284
TI  - Selective inhibition by E4080, a novel bradycardic agent, of positive
      chronotropic responses to norepinephrine in isolated dog hearts.
AB  - E4080, a novel bradycardic agent acts on various ionic currents including the
      hyperpolarization-activated inward current (I(f)), L-type Ca2+ current (ICa) and
      ATP-sensitive K+ (K+ATP) current in mammalian heart and vascular tissues. We thus
      investigated the chronotropic and inotropic effects of E4080 and its interaction
      with the positive cardiac responses to norepinephrine, 3-isobutyl-1-methyl
      xanthine (IBMX) and Bay k 8644 in the isolated, blood-perfused dog right atria
      and left ventricles. E4080 (0.01-1 mumol) decreased the sinus rate and atrial and
      ventricular contractile forces in a dose-related manner. Glibenclamide (3 mumol)
      partly blocked the decrease in atrial force but not the decreases in sinus rate
      and ventricular force induced by E4080. Atropine (10 nmol) did not affect the
      negative cardiac responses to E4080. E4080 (0.01-1 mumol) inhibited the positive
      chronotropic responses to norepinephrine and IBMX dose dependently, but did not
      inhibit the positive inotropic ones in isolated atria. E4080 affected neither
      positive chronotropic nor inotropic responses to Bay k 8644. These results
      suggest that (1) the activation of K+ATP channels by E4080 is partly related to
      the decrease in atrial force but not the decreases in sinus rate and ventricular
      force, and (2) the selective inhibition of E4080 of the cyclic AMP-dependent
      positive chronotropic responses but not inotropic ones is probably due to the
      inhibition of I(f) rather than other properties, e.g., activation of K+ATP
      channels and inhibition of ICa in the dog heart.

PMID- 7509285
TI  - Effect of scyliorhinin I and synthetic scyliorhinin I derivatives at mammalian
      tachykinin NK1, NK2 and NK3 receptors.
AB  - The dogfish tachykinin peptide scyliorhinin I and a number of its analogues
      substituted in position 7 were tested in bioassays for tachykinin NK1, NK2 and
      NK3 receptors. Scyliorhinin I behaved as a full agonist at tachykinin NK1
      receptors of the guinea-pig ileum longitudinal muscle and at NK2 receptors of the
      rabbit pulmonary artery and hamster trachea. In these three preparations
      scyliorhinin I was as potent agonist as substance P methylester and neurokinin A,
      respectively. Evidence for activation of tachykinin NK1 and NK2 receptors by
      scyliorhinin I was obtained by using the selective tachykinin antagonists FK 888,
      MEN 10,376 and L 659,877. Scyliorhinin I was poorly active as an agonist at NK3
      receptors of the rat portal vein. Among scyliorhinin I analogues, [beta-(2
      naphthyl)-Ala7]scyliorhinin I, [Val7]scyliorhinin I and [Ile7]scyliorhinin I were
      3-25 times weaker than scyliorhinin I itself at NK1 and NK2 receptors.
      [Phe7]scyliorhinin I, [Phe(F)7]scyliorhinin I and [Phe(Cl)7]scyliorhinin I were
      as potent as scyliorhinin I at NK1 receptors in the guinea-pig ileum, while they
      showed 10-30 times lower affinity than scyliorhinin I for NK2 receptors. The
      present results are discussed in relation to the importance of position 7 in
      determining the potency and selectivity of scyliorhinin I analogues at tachykinin
      receptors.

PMID- 7509286
TI  - In vitro and in vivo biological activities of SR140333, a novel potent non
      peptide tachykinin NK1 receptor antagonist.
AB  - (S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pip eridin-3-
      yl]ethyl)-4-phenyl-1-azoniabicyclo[2.2.2]octane chloride (SR140333) is a new non
      peptide antagonist of tachykinin NK1 receptors. SR140333 potently, selectively
      and competitively inhibited substance P binding to NK1 receptors from various
      animal species, including humans. In vitro, it was a potent antagonist in
      functional assays for NK1 receptors such as [Sar9,Met(O2)11]substance P-induced
      endothelium-dependent relaxation of rabbit pulmonary artery and contraction of
      guinea-pig ileum. Up to 1 microM, it had no effect in bioassays for NK2 ([beta
      Ala8]neurokinin A-induced contraction of endothelium-deprived rabbit pulmonary
      artery) and NK3 ([MePhe7]neurokinin B-induced contraction of rat portal vein)
      receptors. The antagonism exerted by SR140333 toward NK1 receptors was apparently
      non-competitive, with pD2' values (antagonism potency evaluated by the negative
      logarithm of the molar concentration of antagonist that produces a 50% reduction
      of the maximal response to the agonist) between 9.65 and 10.16 in the different
      assays. SR140333 also blocked in vitro [Sar9,Met(O2)11]substance P-induced
      release of acetylcholine from rat striatum. In vivo, SR140333 exerted highly
      potent antagonism toward [Sar9,Met(O2)11]substance P-induced hypotension in dogs
      (ED50 = 3 micrograms/kg i.v.), bronchoconstriction in guinea-pig (ED50 = 42
      micrograms/kg i.v.) and plasma extravasation in rats (ED50 = 7 micrograms/kg
      i.v.). Finally, it also blocked the activation of rat thalamic neurons after
      nociceptive stimulation (ED50 = 0.2 micrograms/kg i.v.).

PMID- 7509287
TI  - Effect of NG-nitro-L-arginine on shock induced by endotoxin and by platelet
      activating factor in dogs.
AB  - When NG-nitro-L-arginine, a nitric oxide synthase inhibitor, administration was
      started 5 min prior to shock induction in anesthetized dogs, a partial
      restoration was observed in endotoxin-induced shock and a complete recovery in
      platelet activating factor (PAF)-induced shock. When NG-nitro-L-arginine infusion
      was started 5 min after shock induction, no significant recovery was observed in
      endotoxin-induced shock and a complete recovery in PAF-induced shock. These data
      indicate that enhanced production of nitric oxide by vascular endothelial cells
      may contribute to endotoxin- or PAF-induced shock and also that some mediators
      including inducible nitric oxide synthase and/or cellular damage might be
      involved in endotoxin-induced shock.

PMID- 7509288
TI  - Interleukin-3 (IL-3) receptors on rhesus monkey bone marrow cells: species
      specificity of human IL-3, binding characteristics, and lack of competition with
      GM-CSF.
AB  - The relative affinity of recombinant human interleukin-3 (IL-3) binding to normal
      rhesus monkey bone marrow cells was found to be 25- to 50-fold less than that of
      homologous IL-3, which explained the species specificity of human IL-3 observed
      when tested in Macaca species. In contrast, only a small difference was found
      between human and rhesus monkey IL-3 in relative binding affinity for receptors
      on human acute myelogenous leukemia (AML) cells, which confirmed that the species
      specificity of IL-3 is largely unidirectional. The biological significance of the
      findings was demonstrated by direct in vivo comparison of the effects of high
      dose recombinant rhesus monkey and human IL-3. The binding characteristics of IL
      3 receptors on rhesus monkey bone marrow and peripheral blood cells were further
      characterized by specific binding of radiolabeled rhesus monkey IL-3. Scatchard
      analysis of two bone marrow samples demonstrated high-affinity IL-3 receptors (25
      and 80 sites/cell, respectively; equilibrium dissociation constants [Kd] of 8 and
      3 pM/L) as well as low-affinity receptors (1070 and 1290 sites/cell; equilibrium
      dissociation constants of 2600 and 1200 pM/L). In addition, IL-3 receptor
      expression was also detected on purified CD34-positive bone marrow cells.
      Competition by human granulocyte-macrophage colony-stimulating factor (GM-CSF) of
      IL-3 binding to high- or low-affinity receptors on rhesus monkey peripheral blood
      and bone marrow cells could not be demonstrated, which may indicate that the
      growth factor-specific alpha-subunits of the GM-CSF and IL-3 receptors are
      expressed predominantly on different cell types.

PMID- 7509289
TI  - Differences in the regulation of specific glycosylation in the pathogenesis of
      paroxysmal nocturnal hemoglobinuria and the Tn-syndrome.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder
      that resembles in several aspects the Tn-syndrome, in which bone marrow-derived
      cells are deficient in mucin-type beta 1,3 galactosyltransferase (beta 1,3Gal-T)
      due to the persistent repression of an intact allele. In the present study, we
      have investigated phytohemagglutinin (PHA)-activated T cells from the peripheral
      blood of an individual with the well-established clinical diagnosis of PNH. Only
      10% of T cells were deficient in surface expression of the
      glycosylphosphatidylinositol (GPI)-linked CD48 antigen; in contrast, 95% of the
      patient's polymorphonuclear leukocytes harbored the defect. The cell-surface
      density of CD48 on unaffected T cells from this patient was two- to three-fold
      higher when compared to PHA-activated normal donor T cells. CD48-negative T cells
      were cloned and shown to belong to the CD4+ or the CD8+ antigenic subset. To test
      for the possibility that in PNH, as in Tn syndrome, gene repression may be
      responsible for the deficiency, CD48- T cell clones were treated with 5
      azacytidine (5-azaC) and sodium n-butyrate (NaB). While such treatment
      reproducibly led to reexpression of a sialylated CD43 epitope on affected Tn
      syndrome T cell clones, these drugs failed to induce reexpression of CD48 on
      affected PNH T cell clones. Our data suggest that despite many similarities,
      different pathogenetic mechanisms are responsible for PNH and Tn-syndrome. These
      CD48- T cell clones are the first to be described and may be useful to define the
      PNH lesion at a biochemical and genetic level.

PMID- 7509290
TI  - Thyroid hormones enhance hypoxia-induced erythropoietin production in vitro.
AB  - Effects of thyroid hormones on the production of erythropoietin (Epo) were
      investigated in isolated perfused rat kidneys and in the human hepatoma cell
      line, HepG2. Epo protein was measured by radioimmunoassay. L-triiodothyronine and
      L-thyroxine stimulated hypoxia-induced Epo formation both in the kidney and in
      HepG2 cells in a dose-dependent fashion. Quantitation of Epo mRNA by competitive
      polymerase chain reaction (PCR) showed that hypoxic HepG2 cells had three-fold
      higher Epo messenger RNA levels when treated with thyroid hormones for 3 hours.
      Measurements of oxygen consumption revealed that this effect was not due to an
      increase in the degree of hypoxia. Thus, apart from the known direct effect on
      erythroid precursors, thyroid hormones appear to stimulate erythropoiesis by a
      noncalorigenic increase in Epo production.

PMID- 7509291
TI  - The effect of recombinant human interleukin-3 and recombinant human granulocyte
      macrophage colony-stimulating factor on Fc gamma receptor expression and antibody
      dependent cellular cytotoxicity of hematopoietic progenitor cells during in vitro
      myeloid maturation.
AB  - Enriched progenitor cell fractions from human bone marrow were induced to undergo
      myeloid maturation in culture using recombinant human interleukin-3 (rhIL-3) and
      granulocyte-macrophage colony stimulating factor (rhGM-CSF). A negative selection
      method using the murine monoclonal antibodies (MABs) PM81 (anti-CD15), AML-2-23
      (anti-CD14), PC251 (anti-CD33), OKT11 (anti-CD2), and SCCL-1 (anti-CD71) and
      immunomagnetic beads coated with sheep anti-mouse IgG (Dynal A.S., Oslo, Norway)
      was used to remove the more mature cellular components of mononuclear cells from
      normal donor bone marrow samples. The resulting fraction of cells contained 35 to
      40% CD34-positive cells, and less than 1% of cells expressed the receptors for
      the constant portion of immunoglobulin G Fc gamma RI or Fc gamma RII. A small
      population (3-5%) expressed Fc gamma RIII on day 0, and these cells were found by
      two-color flow cytometry to be primarily natural killer (NK) cells. The level of
      Fc gamma R expression was determined every 2 to 3 days on aliquots of the
      differentiating cells. Thirteen percent of the cultured bone marrow cells
      expressed Fc gamma RII after 48 hours in liquid culture with rhIL-3 and rhGM-CSF.
      The percent of cells expressing Fc gamma RII increased to a peak of 78% of the
      gated population on day 10. The mean fluorescence intensity (MFI) remained low
      for the first 8 to 10 days of culture, but at that time the MFI more than
      doubled. Fc gamma RI and Fc gamma RIII expression remained low throughout the
      culture period. The ability of the differentiating cells to perform antibody
      dependent cellular cytotoxicity (ADCC) was determined at a single-cell level in a
      modified plaque assay using monolayers of ox erythrocyte (oxE) target cells. The
      purified progenitor cells, when placed in oxE monolayers sensitized with
      polyclonal rabbit anti-oxE antibody (AB), showed no plaque formation over control
      oxE layers. No increase in ability to generate cytolytic plaques in antibody
      sensitized oxE layers was seen compared with unsensitized oxE layers until after
      10 days of incubation in liquid culture. At that time, the percent of cells
      forming plaques in the AB-sensitized oxE layers was 34.4 +/- 10.7% (average +/-
      standard error of the mean [SEM]; n = 4) compared with 10.0 +/- 0.7% on the
      control oxE layers. The peak plaque formation appeared to coincide with the
      increase in MFI of a large population of the cultured cells.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7509292
TI  - Engraftment with peripheral blood stem cells using noncontrolled-rate
      cryopreservation: comparison with autologous bone marrow transplantation.
AB  - Peripheral blood stem cells (PBSC) are used increasingly as a source of stem cell
      support following myeloablative therapy. In this report, the results of 33
      patients undergoing PBSC transplantation were compared to 17 concurrent patients
      undergoing autologous bone marrow transplantation (ABMT). PBSC were cryopreserved
      using 6% pentastarch and 5% dimethyl sulfoxide (DMSO) with noncontrolled-rate
      freezing. Many patients in the PBSC group were selected because they were
      excluded as candidates for ABMT due to prior pelvic irradiation, marrow tumor
      involvement, or other factors. PBSC were mobilized with high-dose
      cyclophosphamide (CY), CY+granulocyte-macrophage colony-stimulating factor (GM
      CSF), or GM-CSF alone. Colony-stimulating factors were not administered after
      transplantation. A median of 7.4 x 10(8) mononuclear cells (MNC)/kg were
      collected containing a median of 3.2 x 10(4) granulocyte-macrophage colony
      forming units (CFU-GM)/kg and 5.7 x 10(4) burst-forming units (BFU-E)/kg. After
      thawing, CFU-GM recovery was 67% and BFU-E recovery was 59%. The thawed, pooled
      PBSC contained 6.4 x 10(6) CD34+ cells/kg. The entire PBSC volume (median 870 mL)
      was infused over a median of 157 minutes. PBSC patients required a median of 15
      days to achieve an ANC of 500/microL and 22 days for a platelet count of
      50,000/microL. Neutrophil recovery was inversely correlated with the number of
      harvested progenitor cells (p = 0.014); the time to achieve a platelet count of
      50,000/microL was inversely associated with CD34+ cells/kg (p = 0.005). PBSC
      transplant patients achieved an ANC of 500/microL 6 days faster (p < 0.05) and
      had a 10-day shorter hospitalization (p < 0.05) than ABMT patients. Use of
      noncontrolled-rate cryopreserved PBSC is associated with faster engraftment and
      shorter hospital duration than ABMT.

PMID- 7509294
TI  - Attenuation of chronic hypoxic pulmonary hypertension in rats by cyclooxygenase
      products and by nitric oxide.
AB  - We wanted to assess the respective roles of arachidonic acid products and nitric
      oxide in the modulation of pulmonary hypertension in chronically hypoxic rats. In
      isolated blood-perfused lungs, the effects of arachidonic acid before and after
      treatment with the cyclooxygenase inhibitor, meclofenamate, were compared in
      control (C) rats and rats exposed for two weeks to 10% oxygen (chronic hypoxia
      CH). Arachidonic acid caused mixed dilator and constrictor effects during both
      normoxia and hypoxia; dilatation was more prominent in chronically hypoxic rats.
      Meclofenamate abolished both dilator and constrictor actions of arachidonic acid;
      it raised baseline, normoxic pulmonary artery pressure, in chronically hypoxic
      but not control rats, which suggests that dilator products of arachidonic acid
      are released in the pulmonary hypertension of chronic hypoxia and attenuate
      pulmonary artery pressure. As shown previously, the nitric oxide synthase
      inhibitor N-nitro-L-arginine methyl ester (L-NAME) raised pressure in chronically
      hypoxic but not control rats. Meclofenamate and L-NAME given in sequence both
      raised pulmonary artery pressure in chronically hypoxic rats and the combined
      rise was substantial (+13 mmHg). We conclude that, in the conditions of our
      experiment, both nitric oxide and dilator prostanoids are released in hypoxic
      pulmonary hypertension in rats. Thus, two synthetic processes, both possibly
      endothelial dependent, may modulate hypoxic pulmonary hypertension.

PMID- 7509293
TI  - The role of granulocyte-macrophage and granulocyte colony-stimulating factors in
      neutrophil transendothelial migration: comparison with interleukin-8.
AB  - Granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF and G
      CSF) have proinflammatory effects on mature neutrophils. Both factors have been
      reported to cause neutrophil chemotaxis and are produced by cells stimulated by
      inflammatory mediators, including endothelial cells. We therefore tested the
      hypothesis that these factors might mediate neutrophil transendothelial
      migration, either by forming a gradient across the endothelial monolayer or
      through the production of CSFs by activated endothelium. Studies of neutrophil
      migration across filters without endothelium showed that migration was promoted
      in the presence of a gradient of either CSF, but was equally promoted against the
      gradient; that is, the CSFs are chemokinetic but not chemotactic. The CSFs
      promoted migration of neutrophils across endothelial monolayers cultured on
      filters, but the magnitude of this effect was very small compared with that of a
      prototypic neutrophil chemoattractant, interleukin-8 (IL-8) (migration index
      [stimulated/unstimulated] 1.8-fold for GM-CSF, 10.8-fold for IL-8). Activation of
      endothelial monolayers by preincubation with tumor necrosis factor-alpha (TNF
      alpha) increased neutrophil transmigration significantly; neutralizing antibodies
      to IL-8 inhibited this increase by 44%, whereas neutralizing anti-GM-CSF
      antibodies did not inhibit it. These data suggest little role for the CSFs in
      neutrophil diapedesis at inflammatory sites in vivo. Exposure of neutrophils to
      GM-CSF decreased their migration through TNF-activated monolayers, whereas G-CSF
      did not. This may have implications for the therapeutic administration of these
      factors.

PMID- 7509295
TI  - Chromosomal localization of the protein tyrosine phosphatase G1 gene and
      characterization of the aberrant transcripts in human colon cancer cells.
AB  - We have recently described the isolation of the human PTPG1 gene which encodes a
      member of intracellular protein tyrosine phosphatases that may be candidates for
      tumor suppressor genes. In order to investigate the abnormality of the PTPG1
      transcript in various human cancer cell lines, we have analyzed the consensus
      catalytic region of PTPG1 cDNA, using the reverse transcription polymerase chain
      reaction. In a colorectal carcinoma cell line, DLD-1, we found three aberrant
      transcripts. Sequencing analysis revealed that one had a missense point mutation
      and the remainders contained 77 bp and 173 bp deletions, respectively. These
      alterations might directly affect their phosphatase activities. Our findings
      provide the first evidence for the aberrant transcripts of the protein tyrosine
      phosphatase in human cancer cells, and suggest that the aberration of PTPG1 gene
      might be involved in the tumorigenesis. Moreover, the human PTPG1 gene is
      localized on chromosome 7q11.23, a region with frequent abnormalities implicated
      in some human cancers.

PMID- 7509296
TI  - Epidermal growth factor induces acrosomal exocytosis in bovine sperm.
AB  - At the time of fertilization mammalian spermatozoa undergo a Ca(2+)-dependent
      exocytotic event, which is known as the acrosome reaction (AR). We describe here
      that EGF-receptor (EGFR) is localized in the head of bull spermatozoa and that
      epidermal growth factor (EGF) can induce the occurrence of the AR in its typical
      dose-dependent manner. Previously we showed that protein kinase C (PKC) is
      involved in the cascade leading to AR in bull spermatozoa. Here, we show that PKC
      is involved in the mechanism in which EGF exerts its effect on AR. These findings
      together with our results which show inhibition of AR by tyrosine-phosphorylation
      inhibitors, indicate that ejaculated bull sperm contain a typical 170-kDa EGFR
      which is active in the mechanism leading to AR.

PMID- 7509297
TI  - Thiol ester role in correct folding and conformation of human alpha 2
      macroglobulin. Properties of recombinant C949S variant.
AB  - To determine the role of the thiol ester in the folding of human alpha 2
      macroglobulin (alpha 2M) in the active conformation, we have characterized a
      recombinant variant of alpha 2M, C949S, expressed in baby hamster kidney cells,
      that lacks the thiol ester-forming cysteine. C949S alpha 2M behaves like
      methylamine-treated plasma alpha 2M, with correctly formed inter-subunit
      disulfide bridges, non-covalent association of covalent dimers to form tetramers,
      and exposure of the receptor binding domain, but an inability to inhibit
      proteinases, and inaccessibility of the bait regions to proteolysis. We concluded
      that correct folding of monomers or their association to give tetrameric alpha 2M
      does not require a pre-formed thiol ester. Active alpha 2M may form in vivo by a
      two-step process involving initial folding to give a structure resembling that of
      C949S alpha 2M followed by thiol ester formation and a conformational change that
      gives the native active state.

PMID- 7509299
TI  - Immunological study in primary intestinal lymphangiectasia.
AB  - Primary intestinal lymphangiectasia is a rare congenital condition associated
      with protein-losing enteropathy. Hypogammaglobulinemia and lymphopenia secondary
      to this condition are frequent but infectious complications are not. So far few
      immunological studies have been made in these patients. We report here the
      results of such a study carried out in two adolescents. Both patients presented
      with a dramatic decrease in serum gammaglobulins, especially IgG and IgA, and in
      peripheral blood lymphocytes, especially CD4 T helper cells. From a functional
      standpoint, the proliferative response to certain mitogens was reduced. A
      decrease in in vitro production of immunoglobulins by B lymphocytes may be due to
      a faulty T/B cell cooperation. Histological examination of duodenal biopsy
      specimens revealed a decreased number of intraepithelial lymphocytes. Colonoscopy
      revealed nodular lymphoid hyperplasia in the terminal ileum, confirmed by
      endoscopic biopsy. The role of these abnormalities in the development of
      infectious complications and lymphoma is underscored.

PMID- 7509300
TI  - [Determination of alpha fetoproteins in patients infected with virus B and C.
      Preliminary report].
AB  - The presence of detectable levels of aFP was investigated through RIA in 78 serum
      samples classified as follows: 32 samples from healthy volunteers (group A), 15
      anti-HCV positive sera, 19 samples from HBV Chronic carriers (Group B), and 12
      sera from a group of anti-core positive individuals, (Group C). Increased aFP
      levels, upper to the calculated maximal limit (Above 2.6 ng/ml) were detected in
      2 individuals from Group A, in 2 HCV positive sera and in 6 HBV chronic carriers.
      None of the Group C demonstrated increased aFP value. Two B positive sera with
      augmented aFP activity showed significantly elevated values of this protein 13
      and 20 fold upper than maximal limit. In Venezuela, aFP levels the HBV chronic
      carriers do not appear to be comparable to the reported values in HBV hyper
      endemic countries. The need to analyze aFP values in normal groups is emphasised.

PMID- 7509298
TI  - Effect of granulocyte-colony stimulating factor in glycogen storage disease type
      Ib.
AB  - Five children with glycogen storage disease type Ib (glycogenosis Ib), a
      metabolic defect associated with neutropenia and impairment of neutrophil
      function, were treated with granulocyte colony stimulating factor, a haemopoietic
      growth factor that induces a significant increase in polymorphonuclear leucocyte
      count in vivo. Recurrent bacterial or fungal infections were recorded in the
      three patients who had very low polymorphonuclear leucocyte counts. Experience at
      this centre indicates that the absolute number of polymorphonuclear leucocytes is
      more important than the alteration of their metabolic function in determining the
      susceptibility of the patients to infection. Granulocyte colony stimulating
      factor was effective at increasing polymorphonuclear leucocyte numbers (and
      restored function to some extent) in patients with glycogenosis Ib. This drug
      might be beneficial in cases of severe infection, in glycogenesis Ib patients
      with neutropenia.

PMID- 7509301
TI  - [Anti-HCV in patients without risk factors for hepatitis C. Prospective study in
      200 patients].
AB  - Using a second generation enzyme immunoassay (ELISA) for the detection of
      antibodies against Hepatitis C virus (HCV), we investigated the frequency of
      antibodies anti-HCV and the Alanine Aminotransferase (ALT) plasma levels of 200
      patients without history of viral hepatitis, liver diseases, blood transfusions,
      intravenous drugs abuse, homosexuality, hemodialysis, infection by Human
      Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), nor workers of health
      services. There plasma samples (1.5%), were positives for antibodies anti-HCV,
      all of these samples were confirmed by RIBA (Recombinant Immunoblot Assay). In
      these three patients, the ALT plasma level were more than two folds the normal
      upper limit, another six patients had high ALT levels but less than one fold the
      normal upper limit. None of the infected patients had any clues that suggested
      the possible way of infection in the clinic history. We concluded that the
      incidence of Hepatitis C in the studied patients is 1.5% and that the ALT levels
      could be used to identify Hepatitis C infection.

PMID- 7509302
TI  - Studies on the structure of the mouse CBF-A gene and properties of a truncated
      CBF-A isoform generated from an alternatively spliced RNA.
AB  - CCAAT-binding factor (CBF), a heteromeric transcription factor that binds to
      sequences containing a CCAAT motif, is composed of three subunits, A, B and C,
      which are all required for DNA binding. The mouse CBF-A gene contains seven
      coding exons, which span 12 kb. Evidence is also presented for an additional 5'
      untranslated exon. The 90-amino-acid (aa) segment of CBF-A, which shows a high
      degree of sequence identity with the yeast transcription factor, HAP3, is split
      into exons 3 and 4. An alternatively spliced RNA that lacks exon 3 was identified
      by polymerase chain reaction. Although removal of exon 3 interrupts the CBF-A
      reading frame, a potential start codon at the 3' end of exon 2 is in the same
      reading frame as the reading frame encoding CBF-A in exons 4 to 7. A CBF-A
      polypeptide of the predicted 17-kDa, size, was indeed identified after in vitro
      transcription and translation of the DNA complementary to RNA (cDNA)
      corresponding to the alternatively spliced CBF-A mRNA. In contrast to full-length
      CBF-A, this truncated CBFA did not bind to a DNA sequence containing the CCAAT
      motif in the presence of the other two components of CBF. This result indicates
      that the segment corresponding to the exons missing in the truncated isoform of
      CBF-A is essential for the binding of CBF to DNA.

PMID- 7509303
TI  - Human cathepsin B-encoding cDNAs: sequence variations in the 3'-untranslated
      region.
AB  - We have isolated two cathepsin B (CTSB)-encoding cDNAs, hCBF1 and hCBF2, from a
      normal human embryonic fibroblast library. These clones demonstrate 98% identity
      to overlapping regions of published human hepatoma and kidney CTSB cDNAs, but
      show some interesting differences from the published sequences in the 3'
      untranslated region (3'-UTR). Both hCBF1 and hCBF2 contain a 10-bp insertion in
      the 3'-UTR that may permit formation of a highly stable stem-loop structure not
      present in mRNAs without this insertion. Our hCBF1 cDNA also contains a 1019-bp
      extension of the 3'-UTR sequence that resembles the long 3'-UTR reported for
      murine CTSB cDNAs. Probes unique to this 3'-UTR extension hybridize to 4.0- and
      1.7-kb CTSB RNAs on Northern blots, but not to the major 2.2-kb mRNA transcript.
      Our data reveal variations in normal human CTSB transcripts that result from
      differences in the length of the 3'-UTR, as well as the presence or absence of a
      stem-loop stabilizing sequence.

PMID- 7509304
TI  - Prognostic factors and impacts of adjuvant therapy in early-stage cervical
      carcinoma with pelvic node metastases.
AB  - Three hundred seventy cases of clinical stage Ib-II cervical carcinoma treated
      with radical abdominal hysterectomy and bilateral pelvic lymphadenectomy at Chang
      Gung Memorial Hospital between 1981-1986 were reviewed retrospectively. Of these,
      105 patients had pelvic lymph node metastases. Clinicopathological variables
      including flow cytometric DNA analysis and the use of adjuvant therapy were
      studied. Recurrence-free survival was significantly worse among patients with
      positive pelvic nodes by parametrial extension, increasing number of positive
      nodes, and DNA index greater than 1.3. In patients with positive nodes and
      negative parametria, the number of positive nodes remained a significant
      predictor of survival. Utilizing these significant variables, we identified three
      distinct risk groups. Those patients who had negative parametria, only one
      positive node, and a DNA index not greater than 1.3 were categorized as the low
      risk group. Those who had either positive parametria or more than three positive
      nodes were categorized as the high-risk group. All the others fell into the
      intermediate-risk group. Five-year recurrence-free survival rates were 84.6,
      71.6, and 42.1%, respectively (P = 0.0006). Applying this risk group
      classification and the significant risk factors, we may select more appropriate
      subsets of patients and good stratification for future prospective trials in
      surgically treated early-stage cervical carcinoma patients with pelvic node
      metastases.

PMID- 7509305
TI  - [Finasteride (Proscar) for benign prostatic hypertrophy].
AB  - Several alternatives to surgery for benign prostatic hypertrophy (BPH) were
      studied during the past few years. Finasteride (Proscar), a 4-azosteroid, is an
      inhibitor of the enzyme 5-alpha reductase, which is responsible for the
      conversion of testosterone to the biologically more active dihydrotestosterone
      (DHT). We report 3 years of experience with the drug in 23 men. Persistent
      significant decreases in serum DHT and prostate-specific antigen (PSA) were
      documented. Prostatic volume decreased by about 25% after 1 year, and remained
      fairly constant thereafter. Urination improved, as evidenced by increased maximal
      flow rate and decreased volume of residual urine. Symptoms were affected
      favorably, but only mildly. One of the main advantages of the drug is its lack of
      side-effects. More data on a larger number of patients with a longer follow-up
      are needed before finasteride can be established as having a role as an
      alternative treatment for BPH.

PMID- 7509306
TI  - [Distribution and function of gp90MEL-14 positive and negative T lymphocytes].
AB  - The expression of gp90MEL-14 molecules on lymphocytes in vitro was extremely
      unstable. Even in the course of usual procedures for preparing single cell
      suspension, the amount of gp90MEL-14 was down-or up-regulated depending on the
      condition. Addition of NaN3 in the medium for preparing cell suspension
      stabilized the level of gp90MEL-14 and enabled to quantify the precise amount of
      gp90MEL-14 on various lymphoid cells, which appeared to reflect the expression
      pattern of gp90MEL-14 in vivo. By using this simple method, it was clearly
      demonstrated that the proportion of gp90MEL-14 positive cells and amount of
      gp90MEL-14 on the cells were associated with the anatomical and functional
      distance from endothelial cells of high endothelial venule in peripheral lymph
      nodes. Furthermore, the expression of gp90MEL-14 showed the reverse association
      with that of Pgp-1. When immunological functions were compared between gp90MEL-14
      positive T cells and gp90MEL-14 negative T cells, the latter gp90MEL-14 negative
      T cells generated higher responses than gp90MEL-14 positive cells in mixed
      lymphocyte reaction. Furthermore, upon stimulation with concanavalin A (Con A),
      phytohaemaggultinin or immobilized anti-CD3 antibodies, gp90MEL-14 negative CD8+T
      cells showed significantly higher proliferative responses and generated extremely
      higher amounts of IL-2 and IFN-gamma than gp90MEL-14 positive CD8+ T cells did.
      By contrast, among the CD4+ T cell subpopulations no difference in the Con A
      response was observed and only slightly higher IL-2 secretion was detected in
      gp90MEL-14 negative CD4+ T cells than in gp90MEL-14 positive cells. The present
      findings demonstrate that gp90MEL-14 negative CD8+ and in some case CD4+ T cells,
      which make up a minor T cell subpopulation in peripheral lymphoid tissues are in
      functionally active state in vivo and may play a different role from major
      gp90MEL-14 positive T cells.

PMID- 7509307
TI  - [Investigation of agretopic motifs in T cell responses specific for pigeon
      cytochrome c related peptides and restricted to I-E molecules].
AB  - In our previous study, epitopic and agretopic residues of a peptide fragment
      deduced from pigeon cytochrome c43-58 (p43-58, AEGFSYTDANKNKGIT) and it's
      analogues in the T cell responses restricted to I-A molecules were determined. It
      has been shown that amino acid residue position 50 of the p43-58 works as an
      epitopic which contacts with T cell antigen receptor (TCR) and residues at
      positions 46 and 54 function as agretopes which contact with I-A molecules. In
      the present study, epitopic and agbretopic sites were analyzed in T cell
      proliferative responses that were restricted to the other class II, I-E,
      molecules. A peptide antigen, 46D50V54R, which had been prepared by substitution
      of amino acids at positions 46, 50 and 54 of p43-58 with aspartic acid (D),
      valine (V) and arginine (R), respectively was shown to induce class II restricted
      T cell responses in B10. A (3R) (I-Ab, I-Eb/k) but not in B10 (I-Ab, I-E-) mice.
      Similarly, 50V50R which had been prepared by substitution of amino acids at
      positions 50 and 54 with V and R, respectively induced T cell proliferation in
      B10. BR mice (I-Ak, I-Ek) but not in B10. A (4R) (I-Ak, I-E-) mice. These
      findings indicate that the 46D50V54R and 50V54R generate I-E restricted
      proliferative responses of T lymphocytes in I-Eb/k and I-Ek-carrying mice,
      respectively. Furthermore, it was shown that residue 50 functions an an epitope
      and residues 46 and 54 as agretopes in the I-E restricted responses. Almost
      identical results were obtained when I-E restricted responses of T lymphocytes
      were analyzed in B10. PL (H-2u) and B10. SM (H-2v) mice. However, sine no I-E
      negative counterpart strain for these two latter strains is available, complete
      analysis concerning the epitopic and agretopic functions has not been performed
      with B10. PL and B10. SM mice. The present findings demonstrate that the
      functional sites of the p43-58 analogues are preserved is the T cell responses
      restricted to each I-E haplotype studied. However, when most potent agretopic
      motif was determined in various mouse strains, the specific amino acid motifs on
      the agretopic positions were different among various I-E haplotypes. Furthermore,
      substitution of the epitopic residue showed no influence on the binding affinity
      between agretopic residues and class II molecules. Thus, these epitope and
      agretopes appear to function independently.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7509309
TI  - Effects of intermittent growth hormone or insulin-like growth factor 1
      administration in the neonatal dwarf rat.
AB  - To further evaluate the role of growth hormone (GH) in the neonatal period, the
      effects of GH or insulin-like growth factor 1 (IGF-1) administration were studied
      in the neonatal GH-deficient rat. Groups of pups from newborn litters were
      randomized to receive twice daily subcutaneous injections of recombinant bovine
      growth hormone (bGH, 5 micrograms), recombinant human IGF-1 (10 micrograms) or
      saline from the second to twelfth day of life. The effects on growth parameters,
      serum IGF-1 concentration, body composition and hepatic GH receptor binding were
      assessed. bGH-treated animals showed increases in body weight gain (p = 0.01),
      serum IGF-1 (p < 0.01), carcass nitrogen (p < 0.001) and carcass water (p <
      0.001) compared to IGF-1 or saline-treated animals. No differences in these
      parameters were noted between IGF-1 and saline-treated groups. bGH-treated
      animals showed a significantly lower hepatic GH receptor binding (p < 0.01)
      compared to the other two groups. The demonstration of anabolic responses to GH
      administration in the neonatal period has implications for the possible role of
      GH in fetal and neonatal growth.

PMID- 7509308
TI  - Growth hormone-binding protein in partially hepatectomized rats.
AB  - The role of the liver in regulating serum growth hormone-binding protein (GH-BP)
      was studied. We measured rat serum GH-BP and insulin-like growth factor 1 (IGF-1)
      30 min to 96 h after 70% partial hepatectomy (PHP) or sham operation in adult
      male rats. Serum GH-BP declined sharply from 5.8 +/- 0.1% at baseline to 3.9 +/-
      0.5% by 48 h following PHP. By 72 h serum GH-BP at baseline to 3.9 +/- 0.5% by 48
      h following PHP. By 72 h serum GH-BP returned to baseline level and remained at
      that level 96 h postoperatively. In sham-operated female rats, serum GH-BP was
      about 2-fold higher than in males (10.5 +/- 1.46 versus 5.8 +/- 0.2%), whereas 24
      h after hepatectomy a significant drop of about 50% was observed (p < 0.001).
      Serum IGF-1 decreased within 2-4 h postoperatively in both sham-operated and PHP
      groups, but thereafter was lower in the PHP rats, up to 48 h after operation,
      compared to sham-operated rats (p < 0.03). The study shows that the liver has an
      important role in the determination of serum GH-BP levels. The return to normal
      GH-BP level, even before the liver regained its full size following hepatectomy,
      suggests an increase in GH-BP production by the regenerating liver.

PMID- 7509311
TI  - Cystic fibrosis in a low-incidence population: two major mutations in Finland.
AB  - The incidence of cystic fibrosis (CF) in Finland, 1:25,000 newborn, is one of the
      lowest in Caucasian populations. The delta F508 mutation accounts for 18/40 (45%)
      of CF chromosomes in Finland. Other mutations were therefore sought among the
      remaining 55%. Twelve out of 40 chromosomes (30%) were found to carry 394delTT,
      whereas G542X and 3732delA were each detected in one chromosome. Eight mutations
      remained unidentified using a testing panel for 26 mutations. Mutation 394delTT
      was associated exclusively with haplotype 23-36-13. Five unknown mutations were
      associated with different haplotypes for microsatellite markers, whereas three
      shared the same haplotype. Most delta F508 mutations and all unidentified
      mutations originated from regions of old and dense settlement in the coastal
      regions, whereas 394delTT was geographically clustered and enriched in a rural
      location, consistent with a local founder effect. The remote location of Finland
      and her population history give a plausible explanation for the rarity of CF in
      Finland.

PMID- 7509312
TI  - Binding of atrial and brain natriuretic peptides to cultured mouse astrocytes
      from different brain regions and effect on cyclic GMP production.
AB  - We prepared primary cultures of mouse astrocytes from the cerebral cortex,
      hypothalamus, and cerebellum to examine the possibility of regional disparity in
      binding of human atrial and porcine brain natriuretic peptides (hANP, pBNP) and
      their effect on cyclic guanosine monophosphate (cGMP) production. 125I-hANP and
      125I-pBNP bound in a specific and saturable manner to all three regions. For both
      peptides, Scatchard analysis suggested a single population of binding sites on
      astrocytes from all three regions. No significant differences were observed in
      the maximal binding capacities (Bmax) or binding dissociation constants (KD)
      between the two peptides in the astrocyte preparations from different regions.
      ANP and BNP also evoked cGMP stimulation in a similar, dose-dependent fashion in
      astrocytes from all three regions, with maximal responses to both peptides
      reached at a concentration above 1 microM. While BNP elicited a greater maximal
      cGMP accumulation than ANP, no difference could be demonstrated in the cGMP
      responses to either peptide between brain regions. Thus we have been unable to
      demonstrate regional heterogeneity in the responsiveness of astrocytes to ANP and
      BNP.

PMID- 7509310
TI  - 394delTT: a Nordic cystic fibrosis mutation.
AB  - In a systematic screening for mutations in the gene encoding the cystic fibrosis
      transmembrane regulator among Danish cystic fibrosis (CF) patients, we identified
      a mutation in exon 3 (394delTT); this mutation was found to be relatively common
      in Denmark. We therefore screened for 394delTT in Sweden and Norway, where it
      turned out to be the second most frequent mutation, accounting for 4% of all CF
      mutations. It also occurs with a high frequency in Finland, but has not been
      found in larger surveys of mutations in the CFTR gene. Thus, 394delTT seems to be
      a specific Nordic CF mutation.

PMID- 7509313
TI  - Antilisterial immunity includes specificity to listeriolysin O (LLO) and non-LLO
      derived determinants.
AB  - Subclinical infection of BALB/c mice with virulent Listeria monocytogenes leads
      to the generation of Listeria-specific T-cell populations required for the
      expression of protective immunity. The L. monocytogenes-produced hemolysin
      listeriolysin O (LLO) is a virulence factor which appears to be crucial for the
      induction of protective antilisterial immunity. Analysis of the specificity of
      antilisterial cytotoxic cells from Listeria-immune BALB/c donors has shown a
      dominant response to an epitope corresponding to amino acids 91 to 99 of LLO.
      Demonstration of antilisterial T cells with specificity to non-LLO-derived
      epitopes has been difficult to achieve because of the requirement of LLO in
      facilitating escape of the bacteria to the cytoplasm of the host cell and the
      apparent dominance of an anti-LLO response in antilisterial immunity. In this
      study we show that antilisterial immunity also includes specificity to non-LLO
      derived determinants. We used as an immunogen an LLO- mutant of L. monocytogenes
      which expresses the hemolysin perfringolysin O (PFO). The LLO- PFO+ L.
      monocytogenes mutant possesses invasive properties similar to those of wild-type
      L. monocytogenes and escape from the phagocytic vacuole because of the activity
      of PFO. We found that J774 target cells infected with the LLO- PFO+ L.
      monocytogenes mutant were lysed by antilisterial cytotoxic T cells obtained from
      BALB/c mice immunized with wild-type L. monocytogenes. In addition, BALB/c mice
      immunized with the LLO- PFO+ L. monocytogenes mutant were immune to challenge
      with LLO+ wild-type L. monocytogenes, a finding indicative of protective
      antilisterial immunity specific to Listeria-derived epitopes other than LLO.
      Spleen cells from BALB/c mice immunized with the LLO- PFO+ L. monocytogenes
      mutant adoptively transferred antilisterial protection to a subsequent challenge
      with wild-type L. monocytogenes. This splenocyte population also contained
      cytotoxic cells which lysed target cells infected with either the LLO- PFO+ L.
      monocytogenes mutant or wild-type LLO+ L. monocytogenes but did not lyse target
      cells infected with an LLO-expressing Bacillus subtilis transformant. These
      results establish that during the immune response to L. monocytogenes, immune
      splenocytes with specificity for LLO and other, non-LLO-derived epitopes develop.
      These non-LLO epitopes serve as targets for antilisterial cytotoxic cells and for
      lymphocytes which adoptively transfer antilisterial immunity.

PMID- 7509315
TI  - Nitric oxide produced during murine listeriosis is protective.
AB  - Nitric oxide (NO) has been shown to be important for intracellular microbiostasis
      in vitro. To determine the role of NO in immune function in vivo, groups of
      C57BL/6 mice were given a sublethal intravenous inoculum of Listeria
      monocytogenes EGD, and their urine was monitored daily for nitrate, the mammalian
      end product of NO metabolism. Urinary nitrate levels peaked at 5 to 10 times the
      basal level on days 5 to 6, when spleen and liver Listeria counts declined most
      steeply, and decreased thereafter, when spleens and livers were nearly sterile.
      Peritoneal macrophages explanted from Listeria-infected mice produced nitrite
      spontaneously, whereas macrophages from uninfected mice did not. The inducible NO
      synthase mRNA was detectable in the spleens of infected mice on days 1 to 4 of
      infection. When Listeria-infected mice were treated orally throughout the
      infection with NG-monomethyl-L-arginine (NMMA), a specific NO synthase inhibitor
      they showed no detectable rise in urinary nitrate excretion. Mean Listeria counts
      in the livers and spleens NMMA-treated mice were 1 to 3 orders of magnitude
      greater than counts in control mice on days 4 through 8 of infection. Compared
      with control mice, NMMA-treated mice also showed worse clinical signs of
      infection, namely, weight loss, hypothermia, decreased food and water intake, and
      decreased urine output. Histologically NMMA-treated mice had many more
      inflammatory foci in their livers and spleens than control mice. The histologic
      observation that mononuclear cells are present at sites of infection suggests
      that inhibiting NO production did not block the flux of macrophages into infected
      viscera. As controls for possible drug toxicity, a group of uninfected mice given
      NMMA orally showed no detrimental effects on weight, temperature, and food and
      water intake. These experiments demonstrate that inhibition of NO production in
      Listeria-infected mice results in an exacerbated infection and thus that NO
      synthesis is important for immune defense against Listeria infection in mice.

PMID- 7509314
TI  - Epitopes shared by unrelated antigens of Borrelia burgdorferi.
AB  - An immunoglobulin M kappa-chain murine monoclonal antibody (CAB) reacted in a
      Western blot (immunoblot) with approximately 30 polypeptides from a whole-cell
      lysate of several American and European Borrelia burgdorferi strains. The
      reactive antigen with the highest M(r) was measured at 93 kDa (p93) and had an
      NH2-terminal sequence identical to the one previously reported for this antigen.
      The lowest reactive antigen had an M(r) of 16,000. All antigens recognized by CAB
      had isoelectric points within a narrow acidic range, between 5.4 and 6.2. Thus,
      the objective of this study was to determine whether the broad reactivity of CAB
      could be due to degradation of the antigen with the highest M(r), since such
      spontaneous degradation of p93 has already been reported, and to determine
      whether CAB could recognize shared epitopes in different antigens. Treatment of
      B. burgdorferi with protease inhibitors did not result in changes in CAB
      reactivity, indicating that if such degradation existed, it was most likely not
      due to the action of endogenous proteases. Likewise, protease treatment of intact
      organisms and recovery of the antigens in the insoluble fraction of a Triton X
      114 partition indicated that they were internal and thus less likely to be
      degraded by experimental procedures. Amino-terminal sequences of other reactive
      polypeptides showed one approximately 72-kDa polypeptide to be identical to the
      DnaK homolog of B. burgdorferi. Two other antigens at approximately 49 and 47 kDa
      were blocked to Edman degradation. Finally, one sequenced polypeptide with a
      molecular mass of approximately 38.5 kDa had a strong identity with
      glyceraldehyde-3-phosphate dehydrogenase of other bacteria and vertebrates. Thus,
      while it cannot be ruled out that some of the CAB reactivity may be due to
      fragmentation of p93, there is strong evidence to indicate the presence of a
      shared epitope in at least three, possibly five, unrelated antigens of B.
      burgdorferi. A linear epitope within amino acid residues 357 to 371 of p93 was
      identified. Evidence is presented for a discontinuous epitope in the carboxy
      terminal region of the DnaK homolog, which bears strong amino acid identity with
      the p93 epitope. The conserved amino acid sequences necessary for these shared
      epitopes indicate possible genetic and/or functional relatedness among these
      various antigens.

PMID- 7509316
TI  - Isotype and antigen specificity of pertussis agglutinins following whole-cell
      pertussis vaccination and infection with Bordetella pertussis.
AB  - Elevated agglutinin titers have been shown to correlate with protection from
      disease following whole-cell pertussis vaccination, but the isotype and antigen
      specificity of human agglutinating antibodies is unknown. In 13 immunoassays,
      immunoglobulin G antifimbria antibodies had the strongest correlation with
      agglutinin titers following culture-proven infection with Bordetella pertussis
      (R' = 0.79; P < 0.0001) and following whole-cell pertussis vaccination (R' =
      0.87, P < 0.0001).

PMID- 7509317
TI  - Immunogenicity of polysaccharides conjugated to peptides containing T- and B-cell
      epitopes.
AB  - To develop a general model of polysaccharide-peptide vaccine, we have
      investigated the efficiency of linear peptides derived from protein SR, and
      adhesin of the I/II protein antigen family of oral streptococci, to act as
      carriers for two T cell-independent polysaccharides: serogroup f polysaccharide
      from Streptococcus mutans OMZ 175 (poly f) and Saccharomyces cerevisiae mannan.
      Peptide 3 (YEKEPTPPTRTPDQ) and peptide 6 (TPEDPTDPTDPQDPSS), accessible on the
      native SR protein as demonstrated by their reactivity in enzyme-linked
      immunosorbent assays with rat antisera raised against protein SR, correspond to
      immunodominant regions of SR. Peptide 3 contains at least one B- and one T-cell
      epitope, as demonstrated by its ability to induce peptide- and SR-specific
      antibody responses without any carrier and to stimulate the proliferation of rat
      lymph node cells primed either with free peptide or native SR, whereas peptide 6
      contains only B-cell epitope(s). Peptide 3 was then covalently coupled though
      reductive amination to either poly f or mannan, and peptide 6 was coupled to poly
      f. Subcutaneous immunizations of rats with poly f-peptide 3 or mannan-peptide 3
      conjugates produced a systemic immunoglobulin M (IgM) and IgG antibody response,
      and the elicited antibodies reacted with free poly f or mannan, peptide 3,
      protein SR, and S. mutans or S. cerevisiae whole cells. Rats immunized with poly
      f-peptide 6 did not develop any antipeptide or anti-SR response. Furthermore, a
      booster immunization of animals with poly f-peptide 3 or mannan-peptide 3
      conjugates induced high titers of anti-peptide 3, anti-poly f, and antimannan
      antibodies, which occurred quickly. The response is anamnestic for the peptide
      and the polysaccharides and is characterized by an Ig switch from IgM to IgG. The
      data presented here confirm that the presence of B- and T-cell epitopes is
      necessary to induce an anamnestic antipeptide response and that a peptide
      containing relevant B- and T-cell epitopes can act as a good carrier in improving
      an antipolysaccharide anamnestic immune response.

PMID- 7509318
TI  - Epitope specificity of rabbit immunoglobulin G (IgG) elicited by pneumococcal
      type 23F synthetic oligosaccharide- and native polysaccharide-protein conjugate
      vaccines: comparison with human anti-polysaccharide 23F IgG.
AB  - Streptococcus pneumoniae type 23F capsular polysaccharide (PS23F) consitss of a
      repeating glycerol-phosphorylated branched tetrasaccharide. The immunogenicities
      of the following related antigens were investigated: (i) a synthetic
      trisaccharide comprising the backbone of one repeating unit, (ii) a synthetic
      tetrasaccharide comprising the complete repeating unit, and (iii) native PS23F
      (all three conjugated to keyhole limpet hemocyanin [KLH]) and (iv) formalin
      killed S. pneumoniae 23F. All antigens except the trisaccharide-KLH conjugate
      induced relatively high anti-PS23F antibody levels in rabbits. The epitope
      specificity of such antibodies was then studied by means of an inhibition
      immunoassay. The alpha(1-->2)-linked L-rhamnose branch was shown to be
      immunodominant for immunoglobulin G (IgG) induced by tetrasaccharide-KLH, PS23F
      KLH, and killed S. pneumoniae 23F: in most sera L-rhamnose totally inhibited the
      binding of IgG to PS23F. Thus, there appears to be no major difference in epitope
      specificity between IgG induced by tetrasaccharide-KLH and that induced by
      antigens containing the polymeric form of PS23F. Human anti-PS23F IgG (either
      vaccine induced or naturally acquired) had a different epitope specificity: none
      of the inhibitors used, including L-rhamnose and tetrasaccharide-KLH, exhibited
      substantial inhibition. These observations suggest that the epitope recognized by
      human IgG on PS23F is larger than the epitope recognized by rabbit IgG. Both
      human and rabbit antisera efficiently opsonized type 23F pneumococci, as measured
      in a phagocytosis assay using human polymorphonuclear leukocytes.

PMID- 7509322
TI  - Internalization and excretion of epidermal growth factor-dextran-associated
      radioactivity in cultured human squamous-carcinoma cells.
AB  - Certain tumor cells, such as squamous carcinomas and gliomas, can have an
      increased number of epidermal-growth-factor (EGF) receptors. The EGF receptors
      can in these cases be targets for toxic conjugates with specific binding. EGF
      based toxic conjugates are potential targeting agents. We have analyzed the
      internalization and excretion of 125I administered in the form of 125I-EGF
      dextran in squamous-carcinoma A431 cells. 125I-EGF without dextran was used for
      comparison. A431 cells have large numbers of EGF receptors and are capable both
      of recycling and of degradation of internalized receptor-ligand complexes. The
      binding of 125I-EGF-dextran and 125I-EGF was receptor-specific, since both
      ligands competed with non-radioactive EGF for binding. The amount of internalized
      125I as a function of time increased continuously within 24 hr following
      administration of radioactivity as 125I-EGF-dextran. The time pattern was quite
      different when 125I-EGF without dextran was applied. In the latter case, the
      amount of internalized radioactivity decreased already after a few hours,
      probably depending on degradation of EGF. Pre-incubation of the cells with 125I
      EGF-dextran or 125I-EGF and analysis of retained and released 125I activity at
      different times after washing showed that the 125I activity was retained for
      longer periods of time when EGF-dextran was used instead of EGF. About 30% of the
      internalized 125I activity was retained after 24 hr when EGF-dextran was used,
      compared with excretion of nearly all the radioactivity within 5 hr when EGF was
      used. In some experiments a high concentration of non-radioactive EGF, 5
      micrograms/ml, was given to the cells after pre-incubation with 125I-EGF-dextran.
      This changed the retention and excretion patterns, so that a larger amount of
      125I was excreted in the macromolecular fraction and a smaller amount of 125I
      activity was retained in the cells. Gel chromatography of the 125I activity
      released into the culture medium showed that the variations in molecular weight
      were larger after administration of a high concentration of non-radioactive EGF,
      most likely due to partial degradation of EGF-dextran. The results regarding
      excretion are in conformity with a model of competition between recycling of EGF
      dextran-EGF-receptor complexes and "trapping" of EGF-dextran in the lysosomes
      followed by slow degradation. For targeting purposes, it is worth noting that the
      radioactivity administered in the form of 125I-EGF-dextran had a longer retention
      time than when 125I-EGF without dextran was used, and that the retention and
      excretion rates could be modified by post-treatment with the receptor ligand
      itself.

PMID- 7509319
TI  - CD4+ T-cell clones obtained from cattle chronically infected with Fasciola
      hepatica and specific for adult worm antigen express both unrestricted and Th2
      cytokine profiles.
AB  - The well-established importance of helper T (Th)-cell subsets in immunity and
      immunoregulation of many experimental helminth infections prompted a detailed
      study of the cellular immune response against Fasciola hepatica in the natural
      bovine host. T-cell lines established from two cattle infected with F. hepatica
      were characterized for the expression of T-cell surface markers and proliferative
      responses against F. hepatica adult worm antigen. Parasite-specific T-cell lines
      contained a mixture of CD4+, CD8+, and gamma/delta T-cell-receptor-bearing T
      cells. However, cell lines containing either fewer than 10% CD8+ T cells or
      depleted of gamma/delta T cells proliferated vigorously against F. hepatica
      antigen, indicating that these T-cell subsets are not required for proliferative
      responses in vitro. Seventeen F. hepatica-specific CD4+ Th-cell clones were
      examined for cytokine expression following concanavalin A stimulation. Biological
      assays to measure interleukin-2 (IL-2) or IL-4, gamma interferon (IFN-gamma), and
      tumor necrosis factor and Northern (RNA) blot analysis to verify the expression
      of IL-2, IL-4, and IFN-gamma revealed that the Th-cell clones expressed a
      spectrum of cytokine profiles. Several Th-cell clones were identified as Th2
      cells by the strong expression of IL-4 but little or no IL-2 or IFN-gamma mRNA.
      The majority of Th-cell clones were classified as Th0 cells by the expression of
      either all three cytokines or combinations of IL-2 and IL-4 or IL-4 and IFN
      gamma. No Th1-cell clones were obtained. All of the Th-cell clones expressed a
      typical memory cell surface phenotype, characterized as CD45Rlow, and all
      expressed the lymph node homing receptor (L selectin). These results are the
      first to describe cytokine responses of F. hepatica-specific T cells obtained
      from infected cattle and extend our previous analysis of Th0 and Th1 cells from
      cattle immune to Babesia bovis (W. C. Brown, V. M. Woods, D. A. E. Dobbelaere,
      and K. S. Logan, Infect. Immun. 61:3273-3281, 1993) to include F. hepatica
      specific Th2 cells.

PMID- 7509321
TI  - Pentoxifylline and CD14 antibody additively inhibit priming of polymorphonuclear
      leukocytes for enhanced release of superoxide by lipopolysaccharide: possible
      mechanism of these actions.
AB  - Lipopolysaccharide (LPS) primes human polymorphonuclear leukocytes (PMN) for
      enhanced O2- production in response to stimulation by N-formyl-methionyl-leucyl
      phenylalanine (fMet-Leu-Phe). Serum factor is essential for priming at lower
      concentrations of LPS. Complexes of LPS and LPS-binding protein are recognized by
      CD14 on PMN. We investigated the effects of a monoclonal antibody against CD14
      (MY4) and of pentoxifylline (POF), a membrane fluidizer, alone and in
      combination, on LPS-LPS-binding protein activation of phospholipase D evidenced
      by increased phosphatidic acid formation. Phosphatidic acid formation and O2-
      production were inhibited by MY4 and POF. Our results suggest that the actions of
      these agents occur at an early step in the excitation-response sequence. In the
      absence of a second stimulus, LPS plus serum caused an increase in the amount of
      Gi alpha 2 associated with the membrane via CD14. POF, however, had no effect on
      Gi alpha 2 in the membrane. POF alone significantly changed the affinity (KD) of
      the fMet-Leu-Phe receptor of PMN (from 25.2 +/- 4.5 nM to 15.2 +/- 2.4 nM [P <
      0.01; n = 4]) at 37 degrees C. The differences between the sites of action of MY4
      and POF may lead to cooperation by these agents for inhibition of priming by LPS
      plus serum for enhanced O2- production. Clinical use of the antibody and POF may
      diminish tissue damage caused by PMN in clinical endotoxic shock.

PMID- 7509323
TI  - Mimicry of a carcinoembryonic antigen epitope by a rat monoclonal anti-idiotype
      antibody.
AB  - Anti-idiotype antibodies (Ab2) that immunologically mimic tumor antigens are
      auspicious agents for the active immunization of cancer patients. We have
      developed W12, a rat monoclonal IgG1 Ab2 to MN-14, a murine anti-carcinoembryonic
      antigen (CEA) monoclonal antibody. W12 is specific for MN-14 and does not react
      with other isotype-matched anti-CEA monoclonal antibodies. Moreover, W12 inhibits
      the binding between MN-14 and CEA. Anti-CEA antibodies can be induced by
      immunization with W12 (but not with control rat IgG) in xenogenic animals (mice
      or rabbits). Immunoblotting studies indicate that the internal image determinant
      borne by W12 is conformational and requires the association of the heavy and
      light chains of the Ab2 molecule. This study indicates that W12 is a potential
      idiotype vaccine in patients with CEA-producing cancers.

PMID- 7509320
TI  - Isolation and characterization of a gene encoding a Chlamydia pneumoniae 76
      kilodalton protein containing a species-specific epitope.
AB  - Chlamydia pneumoniae is a human respiratory pathogen. Unlike the other two
      Chlamydia species, no species-specific antigen has been defined for C.
      pneumoniae. An immunoreactive clone containing a 0.8-kb fragment was isolated
      from a C. pneumoniae (AR-39) genomic library by using anti-C. pneumoniae rabbit
      immune serum. By Southern hybridization analysis of chromosomal digests of the
      different Chlamydia spp., the 0.8-kb fragment was shown to react specifically
      with C. pneumoniae. Subcloning of this fragment into the pGEX-1 lambda T
      expression vector resulted in the expression of a 62-kDa fusion protein. This
      fusion protein as well as the cleaved C. pneumoniae peptide were recognized by
      anti-C. pneumoniae rabbit immune serum, while the glutathione S-transferase
      moiety was not recognized. The fusion protein was used to produce monospecific
      rabbit antiserum. This antiserum was shown to react with a 76-kDa protein in all
      C. pneumoniae isolates tested, specifically recognize C. pneumoniae inclusions in
      tissue culture, and neutralize infectivity of C. pneumoniae in cell culture. No
      reactivity was observed with Chlamydia trachomatis or Chlamydia psittaci. To
      isolate the entire coding sequence of the 76-kDa protein, two partially
      overlapping fragments of C. pneumoniae DNA, a 3.2-kb HindIII fragment and a 1.2
      kb PvuII fragment, were isolated, cloned, and sequenced. No significant sequence
      similarity was found with any previously reported nucleotide or amino acid
      sequence of the other Chlamydia species. This C. pneumoniae protein containing a
      species-specific epitope could play a role in pathogenesis and may be useful as a
      diagnostic tool.

PMID- 7509324
TI  - Internal image anti-idiotype antibodies related to renal-cell carcinoma
      associated antigen G250.
AB  - The potential usefulness of internal-image anti-idiotype antibodies (Ab2s) in
      modulating hosts' immune responses to tumor-associated antigen (TAA) have
      stimulated considerable interest in the development and characterization of Ab2s.
      Six different mouse monoclonal Ab2s (NUH31, 44, 51, 71, 82 and 91) were generated
      against murine monoclonal antibody G250 (MAbG250) which recognizes a human renal
      cell carcinoma-associated antigen. All 6 Ab2s showed specificity for the MAbG250
      paratope in Western-blot analysis. In inhibition assays, all Ab2s were able to
      compete with the nominal antigen, albeit with differing efficiency. Based on
      cross-blocking studies for idiotope mapping, the Ab2s could be divided into 2
      groups (group I; NUH31, 51, 71, group 2; NUH44, 82, 91). However, cross
      reactivity between these 2 groups was observed, indicating that they recognized
      partly overlapping epitopes on the paratope of MAbG250. Sera from rabbits
      immunized with Ab2s showed reactivity with G250 antigen-positive cell lysates,
      but not with antigen-negative cell lysates. Additional studies revealed that all
      Ab2s were able to induce anti-anti-idiotype antibodies resembling MAbG250 (Ab1').
      These findings suggest that the Ab2s functionally mimic the original G250 antigen
      and may be of use in the immunotherapy of human renal-cell carcinoma.

PMID- 7509325
TI  - Left ventricular mass, serum electrolyte levels and cardiac arrhythmias in
      patients with mild hypertension treated with cilazapril or hydrochlorothiazide.
AB  - Thirty-five patients with mild hypertension (WHO Class I) participated in a
      double-blind cross-over study involving two 8-week periods of treatment with
      cilazapril 2.5-5 mg once daily or hydrochlorothiazide 25-50 mg once daily, in
      each case preceded by a 4-week placebo period. Thirty-two patients completed the
      study, the aim of which was to compare the effects of the drugs on serum
      electrolyte levels, left ventricular mass and cardiac arrhythmias, as assessed by
      echocardiography and 48-h Holter monitoring. Both drugs significantly reduced
      systolic (P < 0.01) and diastolic (P < 0.001) blood pressures (comparisons with
      placebo periods). Cilazapril and hydrochlorothiazide had opposite effects on
      ventricular ectopic activity. The beneficial effect of cilazapril on ventricular
      extrasystole counts correlated significantly (P < 0.001) with the reduction of
      left ventricular mass index. Hydrochlorothiazide had no effects on left
      ventricular mass or diastolic function. Serum potassium values were significantly
      (P < 0.001) reduced by hydrochlorothiazide but there was no correlation between
      changes in potassium levels and changes in ventricular ectopic activity. The
      results of the study suggest that hydrochlorothiazide and cilazapril were equally
      effective in reducing blood pressure, but only cilazapril reduced left
      ventricular hypertrophy and suppressed ventricular ectopic activity.

PMID- 7509326
TI  - Species differences in choroidal vasodilative innervation: evidence for specific
      intrinsic nitrergic and VIP-positive neurons in the human eye.
AB  - PURPOSE: There is evidence that vasodilation of choroidal vessels results from
      facial nerve stimulation. To obtain more information about the role of this
      innervation, the authors examined the presence and spatial organization of
      nitrergic and vasoactive intestinal peptide (VIP) immunoreactive nerves in the
      human choroid. For comparison, the choroid of rabbit and rat eyes, with different
      types of retinal vascularization and no fovea, were studied. METHODS: Whole
      mounts of five human, nine rat, and two rabbit choroids were stained for NADPH
      diaphorase. In addition, immunocytochemical staining was carried out on
      tangential frozen sections of two human choroids using antibodies against nitric
      oxide synthase (NOS), synaptophysin, and VIP. RESULTS: In all species, a
      perivascular network of diaphorase-positive nerve fibers with varicose terminals
      accompanied the arteries and arterioles of the choroidal stroma. A striking
      difference to rat and rabbit choroids was the presence of numerous positively
      stained ganglion cells in human choroids. Positively stained axons connected the
      neurons with each other and with the perivascular network. Most of the ganglion
      cells were concentrated in the temporal-central region, adjacent to the fovea.
      Immunocytochemically, the choroidal ganglion cells were immunoreactive for NOS.
      Some ganglion cells stained for VIP. Staining for synaptophysin demonstrated
      varicose terminals innervating the perikarya of the ganglion cells. Many of these
      terminals stained for NOS and VIP. CONCLUSIONS: The presence of an intrinsic
      nerve cell plexus that is specifically localized in human eyes in the temporal
      central portion of the choroid indicates a functional significance of the
      nitrergic choroidal innervation for the fovea.

PMID- 7509327
TI  - Enhancement of retinal recovery by conjugated deferoxamine after ischemia
      reperfusion.
AB  - PURPOSE: Although toxic to the retina in its native form, the iron chelator
      deferoxamine (DFO) shows no apparent retinal toxicity when bound to hydroxyethyl
      starch (HES). Conjugation of DFO does not alter its iron binding properties. Once
      bound, iron is no longer active in the production of toxic oxygen intermediates.
      This investigation seeks to determine whether HES-conjugated DFO (HES-DFO)
      protects against ischemia-reperfusion injury in the retina. METHODS: Retinal
      ischemia was induced in cats, pretreated with HES-DFO, using both the vascular
      ligation and the increased intraocular pressure models. Retinal recovery was
      monitored by electroretinography. Fundal fluorescein angiography was performed in
      treated and untreated animals after ischemia-reperfusion. RESULTS: Our results
      indicate that pretreatment with an intravenous bolus of HES-DFO, significantly
      enhances recovery of the postischemic b-wave and decreases fluorescein leakage
      after ischemia-reperfusion. CONCLUSIONS: HES-DFO improves recovery of the neural
      retina after ischemia-reperfusion. It also maintains the integrity of the blood
      retinal barrier. The protective effect of HES-DFO on the blood-retinal barrier is
      consistent with its intravascular confinement. That HES-DFO results in protection
      of the neural retina underscores the importance of the blood-retinal barrier as a
      mediator of ischemia-reperfusion injury. HES-DFO may have a role in the early
      management of ischemic retinal disease both as an iron chelator and as a blood
      retinal barrier protector.

PMID- 7509328
TI  - Microwave-assisted staining of mucosal mast cells and granulated intra-epithelial
      lymphocytes after formalin fixation.
AB  - Rat jejunum was fixed with either formalin or methanol-formalin acetic acid
      (MFAA) and stained with Astra Blue or Alcian Blue with or without microwave
      irradiation. Staining of both mucosal mast cells and granulated intra-epithelial
      lymphocytes after formalin fixation was considerably improved by microwave
      irradiation. On the other hand, microwave irradiation slightly impaired staining
      of mucosal mast cells (MMC) and even more strongly granulated intra-epithelial
      lymphocytes (GIEL) after MFAA fixation.

PMID- 7509329
TI  - Quantitative effect of combined chemotherapy and fractionated radiotherapy on the
      incidence of radiation-induced lung damage: a prospective clinical study.
AB  - PURPOSE: The objective of this work was to assess the incidence of radiological
      changes compatible with radiation-induced lung damage as determined by computed
      tomography (CT), and subsequently calculate the dose effect factors (DEF) for
      specified chemotherapeutic regimens. METHODS AND MATERIALS: A prospective,
      clinical study was conducted to determine the response of normal lung tissue to
      combined chemotherapy and radiotherapy. Radiation treatments were administered
      once daily, 5 days-per-week. Six clinical protocols were evaluated: ABVD
      (adriamycin, bleomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions;
      MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) followed by 35
      Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosphamide, adriamycin,
      and vincristine) followed by 25 Gy in 10; and 5-FU (5-fluorouracil) concurrent
      with either 50-52 Gy in 20-21 or 30-36 Gy in 10-15 fractions. CT examinations
      were taken before and at predetermined intervals following radiotherapy. CT
      evidence for the development of radiation-induced damage was defined as an
      increase in lung density within the irradiated volume. The radiation dose to lung
      was calculated using a CT-based algorithm to account for tissue inhomogeneities.
      Different fractionation schedules were converted using two isoeffect models, the
      estimated single dose (ED) and the normalized total dose (NTD). RESULTS: A total
      of 102 patients were entered and 70 completed the study. Forty-two patients
      developed CT changes compatible with lung damage. The actuarial incidence of
      radiological pneumonitis was 71% for the ABVD, 49% for MOPP, 52% for MOPP/ABVD,
      67% for CAV, 73% for 5-FU radical, and 58% for 5-FU palliative protocols.
      Depending on the isoeffect model selected and the method of analysis, the DEF was
      1.11-1.14 for the ABVD, 0.96-0.97 for the MOPP, 0.96-1.02 for the MOPP/ABVD, 1.03
      1.10 for the CAV, 0.74-0.79 for the 5-FU radical, and 0.94 for the 5-FU
      palliative protocols. CONCLUSION: Quantitative dose effect factors (DEF) were
      measured by comparing the incidences of CT-observed lung damage in patients
      receiving chemotherapy and radiotherapy to those receiving radiotherapy alone.
      The addition of ABVD or CAV appeared to reduce the tolerance of lung to
      radiation.

PMID- 7509330
TI  - High dose rate afterloading intraluminal brachytherapy in malignant airway
      obstruction of lung cancer.
AB  - PURPOSE: This is a retrospective study to review the palliation rate, survival
      rate and complications of high dose rate (HDR) intraluminal brachytherapy in the
      treatment of malignant airway obstruction of lung cancer. METHODS AND MATERIALS:
      A total of 225 high dose rate (HDR) brachytherapy treatments were delivered to 76
      patients with symptomatic malignant airway obstruction by remote afterloading
      technique. An average of 7 Gy at a radius of 1 cm from the center of the source
      was delivered by Iridium-192 (Ir-192) sources. The majority of the patients
      received 3 fractions at 2 week intervals. Fifty-four patients received HDR
      brachytherapy as part of their initial treatment; 20 patients presented as
      symptomatic endobronchial recurrence. Two patients received YAG laser
      photoresection to open up the obstruction to allow insertion of the brachytherapy
      catheter. Fifty-nine patients received concurrent external beam irradiation.
      Forty-two patients were given 60-70 Gy in 6-7 weeks with curative intent.
      Seventeen patients were given 20-59 Gy in 2-5 weeks as a palliative measure. Nine
      patients received a radiosensitizer. One patient received concurrent
      chemotherapy. RESULTS: The symptomatic response rates are as follows: dyspnea had
      an 87% response rate (59% partial response, 28% complete response), cough had a
      79% response rate (47% partial response, 32% complete response), hemoptysis had a
      95% response rate (38% partial response, 57% complete response), and
      postobstructive pneumonia had an 88% response rate (53% partial response, 35%
      complete response). Sixty-six patients had follow up endoscopic examination (1-3
      months after brachytherapy). Their total response rate was 87% (52% partial
      response and 35% complete response). There were four acute complications: three
      cases of massive hemoptysis and one of mild hemoptysis. There are five late
      complications: three cases of radiation pneumonitis and two of esophagitis. At
      the time of this study, 55 patients have died with the maximum survival duration
      113 months (9.4 years) from diagnosis date and 18 months from first HDR
      treatment. Twenty-one patients are still alive with a mean follow-up duration of
      20 months from diagnosis date and 7.8 months from the first HDR treatment.
      CONCLUSION: HDR brachytherapy is an excellent modality for palliating symptomatic
      malignant airway obstruction with an acceptable complication rate; however, no
      definitive increase of survival rate was observed. Prospective clinical trials
      are needed to better define its merit regarding survival. This paper also
      includes a literature review and discussion of HDR brachytherapy on bronchogenic
      cancer.

PMID- 7509331
TI  - High dose rate brachytherapy of lung cancer: cure or palliation.

PMID- 7509332
TI  - Combined organ of Corti/modiolus technique for preparing mammalian cochleas for
      quantitative microscopy.
AB  - An improved cochlear preparation technique is described with the following key
      features: 1) Preservation of the organ of Corti (OC) and the spiral ganglion
      cells (SGCs) in the same cochlea for quantitative, high-resolution microscopic
      evaluation; 2) Dissection of the plastic-embedded cochlea so that the entire OC
      can be prepared as whole mounts for quantitative study while the modiolus remains
      in a single block; 3) Decalcification and serial sectioning of the modiolus so
      that all SGC bodies are available for microscopic examination. This technique
      will be valuable for correlating the condition of the OC, nerve terminals, nerve
      fibers and the SGC bodies in normal and damaged cochleas.

PMID- 7509333
TI  - Substance P increases cochlear blood flow without changing cochlear
      electrophysiology in rats.
AB  - Carotid artery infusions of substance P yielded reductions in systemic blood
      pressure and elevations in cochlear blood flow (CoBF), measured via laser Doppler
      flowmeter, with no alterations in cochlear action potentials or cochlear
      microphonics in Wistar-Kyoto rats. Additionally, direct micro-infusions of
      substance P into the anterior inferior cerebellar artery, which contributes to
      the local vascular perfusion of the cochlea, yielded elevations in CoBF with no
      changes in systemic blood pressure. Pretreatment with a specific substance P
      receptor antagonist, ([D-Pro2,D-Trp7,9]SP) via the carotid artery or the anterior
      inferior cerebellar artery, diminished subsequent substance P-induced vascular
      responses. These results suggest that endogenous substance P, like other
      vasoactive peptides, may interact with a substance P-specific receptor population
      in the cochlea and may therefore participate in the ongoing regulation of CoBF.
      These findings also support the premise that vasodilatory hormones, along with
      vasoconstrictive agents, may be involved in the autoregulation of CoBF.

PMID- 7509334
TI  - The diameters of guinea pig auditory nerve fibres: distribution and correlation
      with spontaneous rate.
AB  - In the mammalian auditory nerve physiological recordings revealed that the
      spontaneous discharge rate of single auditory fibres correlates with the
      diversity of input-output functions which may be important for intensity
      discrimination (e.g., Sachs and Abbas, 1974, Liberman, 1978; Winter et al.,
      1990). In this study we determined if the spontaneous discharge rate of auditory
      nerve fibres in the guinea pig is correlated with an anatomical feature, namely
      the diameter of the respective fibres. The diameter of myelinated (Type I) guinea
      pig auditory nerve fibres was measured after staining with different techniques.
      Measurements were made on semithin sections using a video image analysis system.
      The diameters of fibres stained with toluidine blue from the portion of the
      auditory nerve containing fibres from the basal turn of the cochlea were found to
      have a normal distribution. Fibres were also labelled with horseradish peroxidase
      by bulk injection into the spiral ganglion. It was found that the presence of
      horseradish peroxidase within the fibres reduced the measured diameter in
      comparison to adjacent unlabelled fibres. A number of fibres were physiologically
      characterized with respect to spontaneous discharge rate and subsequently
      intracellularly labelled with horseradish peroxidase. Fibre diameter of a
      selected sample of intracellularly fibres was measured over a distance of 800
      microns within the internal auditory meatus. At the positions nearest to the
      spiral ganglion fibres possessing low spontaneous rates were found to have
      smaller diameters than high spontaneous rate fibres. No difference in fibre
      diameter was found for the positions near the cochlear nucleus.

PMID- 7509335
TI  - Translation through an uncDC mRNA secondary structure governs the level of uncC
      expression in Escherichia coli.
AB  - Escherichia coli expresses the beta and epsilon subunits of F1F0-ATP synthase at
      relative levels consistent with the 3:1 (beta/epsilon) stoichiometry in the
      holoenzyme. The mechanism of translational control of expression of the uncC gene
      (epsilon subunit) relative to the immediately 5' uncD gene (beta subunit) was
      examined. Previous expression studies and a computer analysis suggested the
      presence of an RNA secondary structure including the 3' end of uncD, the uncDC
      intergenic region, and the uncC Shine-Dalgarno sequence (S. D. Dunn and H. G.
      Dallmann, J. Bacteriol. 172:2782-2784, 1990). Analysis of in vitro-transcribed
      RNA by cleavage with RNases T1, V1, and CL3 and by chemical modification with
      dimethyl sulfate and diethyl pyrocarbonate confirmed a predicted structure.
      Introduction of premature uncD stop codons inserted 5' of the secondary structure
      strongly reduced epsilon expression, whereas stop codons inserted at positions
      within the secondary structure showed smaller effects, indicating that
      translational control of epsilon synthesis involves partial coupling to beta
      synthesis. Possible mechanisms by which the RNA secondary structure and the
      unfolding of this structure by translation of uncD may govern the level of uncC
      expression are discussed.

PMID- 7509336
TI  - The femC locus of Staphylococcus aureus required for methicillin resistance
      includes the glutamine synthetase operon.
AB  - Tn551 insertional inactivation of femC is known to reduce methicillin resistance
      levels in methicillin-resistant and -susceptible Staphylococcus aureus. By use of
      cotransductional crosses, femC was mapped close to thrB on the SmaI-A fragment of
      the S. aureus NCTC 8325 chromosome. The Tn551 insertion femC::omega 2005 was
      found to interrupt an open reading frame coding for a putative protein of 121
      amino acids which is highly similar to the glutamine synthetase repressors (GlnR)
      of Bacillus spp. Downstream of femC, an open reading frame highly similar to
      Bacillus sp. glutamine synthetases (GlnA) was found. Northern (RNA) blots probed
      with putative glnR or glnA fragments revealed that 1.7- and 1.9-kb transcripts
      characteristic of wild-type cells were replaced by less abundant 7.0- and 7.2-kb
      transcripts in the femC::omega 2005 mutant. Total glutamine synthetase activity
      was also decreased in the mutant strain; the addition of glutamine to defined
      media restored the wild-type methicillin resistance phenotype of the femC mutant.
      This result suggests that the omega 2005 insertion in glnR has a polar effect on
      glnA and that glnR and glnA are transcribed together as an operon. These results
      suggest that the loss of wild-type levels of glutamine synthetase and the
      consequent decrease in glutamine availability cause a decreased level of
      methicillin resistance.

PMID- 7509338
TI  - Nitric oxide synthase inhibition and cerebrovascular regulation.
AB  - There is increasing evidence that nitric oxide (NO) is an important molecular
      messenger involved in a wide variety of biological processes. Recent data suggest
      that NO is also involved in the regulation of the cerebral circulation. Thus, NO
      participants in the maintenance of resting cerebrovascular tone and may play an
      important role in selected vasodilator responses of the cerebral circulation.
      Furthermore, evidence has been presented suggesting that NO participates in the
      mechanisms of cerebral ischemic damage. Despite the widespread attention that NO
      has captured in recent years and the large number of studies that have been
      published on the subject, there is considerable controversy regarding the role of
      this agent in cerebrovascular regulation and in ischemic damage. In this paper
      the results of investigations on NO and the cerebral circulation are reviewed and
      the evidence for and against a role of NO is critically examined.

PMID- 7509337
TI  - The complete amino acid sequence of subunit d of rat liver mitochondrial H(+)-ATP
      synthase.
AB  - Subunit d of H(+)-ATP synthase from rat liver mitochondria was isolated from the
      purified enzyme by reverse-phase high performance liquid chromatography. The
      partial amino acid sequence of the subunit was determined by automated Edman
      degradation of the peptide fragments. The nucleotide sequence of subunit d of rat
      liver H(+)-ATP synthase was determined from a recombinant cDNA clone isolated by
      screening a rat hepatoma cell line H4TG cDNA library with a probe DNA. The
      sequence was composed of 581 nucleotides including a coding region for the import
      precursor of subunit d and noncoding regions on the 5'- and 3'- sides. The
      possible precursor of subunit d and its mature polypeptide deduced from the open
      reading frame consisted of 161 and 160 amino acid residues with molecular weights
      of 18,763 and 18,631, respectively. Subunit d is a hydrophilic protein with an
      isoelectric point of 6.19. The sequence of the rat subunit d is highly homologous
      with that of subunit d of bovine heart and slightly similar to that of the
      subunit d of the yeast mitochondria. However, it had no homology with the
      sequence of any of the subunits of bacterial or chloroplast H(+)-ATP synthase.

PMID- 7509339
TI  - Delayed treatment with AMPA, but not NMDA, antagonists reduces neocortical
      infarction.
AB  - We tested the abilities of two potent non-N-methyl-D-aspartate (non-NMDA)
      glutamate antagonists [2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline
      (NBQX)] and [1-(4-aminophenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazep
      ine hydrochloride (GYKI 52466)] to reduce neocortical infarction following 2 h of
      transient middle cerebral artery occlusion in a hypertensive stroke model in the
      rat and compared these effects against, and in combination with, a potent NMDA
      antagonist [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-amine
      maleate (MK-801)]. In Expt. 1, an already established cytoprotective dose of
      Na(+)-NBQX (30 mg/kg i.p. x 3) was compared with saline (1 ml), the NMDA
      antagonist MK-801 (1 mg/kg i.p. x 3), and a combination of the same doses of both
      NBQX and MK-801. Initial doses were delayed to 90 min following occlusion with
      subsequent injections at the time of reperfusion and 30 min following
      reperfusion. Saline-treated rats sustained 181 +/- 32 mm3 (n = 15) of neocortical
      infarction (mean +/- SD). This was significantly reduced by NBQX to 137 +/- 25
      mm3 (n = 15, p < 0.05) of damage. Neither MK-801 (170 +/- 33 mm3; n = 11) nor the
      combination of MK-801 and NBQX (169 +/- 20 mm3; n = 6) proved to be
      cytoprotective when given with a 90-min delay. In Expt. 2, NBQX (30 mg/kg) was
      dissolved (6 mg/ml) in 5% dextrose and compared with both saline and dextrose
      (1.2 ml) i.v. infusions given over a 4-h period starting 1 h after occlusion.
      Saline-treated rats had a mean infarct of 183 +/- 27 mm3 (n = 6), dextrose
      treated had 200 +/- 30 mm3 (n = 9), while for NBQX-treated rats it was reduced to
      129 +/- 60 mm3 (n = 10, p < 0.05). Intravenous NBQX precipitated into the renal
      tubules, causing nephrotoxicity. In Expt. 3, rats were given either saline (1 ml
      i.p.) or GYKI 52466 (10 mg/kg i.p.) at 30 and 90 min following occlusion and at
      30, 90, and 150 min following reperfusion. Saline-treated rats sustained 187 +/-
      27 mm3 of neocortical infarction (n = 7), while those treated with GYKI 52466
      were protected, with 139 +/- 38 mm3 of infarction (n = 7, p < 0.05). A clinically
      useful role for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate antagonists
      in embolic stroke is envisaged if nontoxic drugs can be developed, since
      cerebroprotection was achieved with delayed treatment with both of these lead
      compounds.

PMID- 7509340
TI  - Cytofluorographic analysis of effects of interferons on expression of human
      cytomegalovirus proteins.
AB  - The appearance of cytomegalovirus (CMV) proteins in infected fibroblasts was
      determined by flow cytometry. The sequential production of immediate early (IE),
      early (E), and late (L) proteins reacting with respective monoclonal antibodies
      (mAbs) E13, 58/5, and 24/4 was determined in fibroblasts infected with the AD-169
      strain of CMV. The percentage of cells expressing CMV proteins and the intensity
      of fluorescence within cells were determined from day 1 to day 7 post-infection.
      The effect of interferons (IFNs) alpha, beta, gamma on expression of CMV proteins
      was analyzed using flow cytometry. IFNs inhibited E and L protein production at
      days 3 and 6 post-infection in a dose-dependent manner. This inhibitory effect on
      protein expression was associated with a reduction in release of infectious CMV
      into culture media. The method described here for detection of CMV proteins using
      flow cytometry may be useful for basic studies of gene expression and for
      diagnostic purposes.

PMID- 7509343
TI  - Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via
      ETB receptor by producing nitric oxide in isolated rat glomerulus, and in
      cultured rat mesangial cells.
AB  - We investigated the effects of endothelins on receptor-mediated cyclic nucleotide
      metabolism in rat glomerulus, inner medullary collecting duct (IMCD), and also in
      cultured rat glomerular mesangial cells. Endothelin (ET)-3 dose-dependently
      stimulated cGMP accumulation in glomerulus, which was higher than that of ET-1 or
      ET-2. ETB receptor agonist IRL 1620 produced cGMP in a dose-dependent manner,
      mimicking the effect of ET-3. ETA receptor antagonist BQ123-Na did not inhibit ET
      3- or IRL 1620-stimulated cGMP generation. NG-monomethyl-L-arginine (L-NMMA)
      significantly inhibited ET-3- or IRL 1620-induced cGMP production, suggesting
      that ET-3- or IRL 1620-stimulated cGMP generation was mediated through nitric
      oxide (NO). Intracellular Ca chelator BAPTA/AM and calmodulin antagonist W-7, but
      not Ca channel blocker nicardipine, significantly inhibited ET-3- or IRL 1620
      induced cGMP generation. In cultured rat mesangial cells, ET-3 stimulated cGMP
      generation through NO in the presence of fetal calf serum, which was not
      inhibited by addition of BQ123-Na. In IMCD, ET-3 had no stimulative effect on
      cGMP generation. We conclude that ET-3 stimulates NO-induced cGMP generation
      through ETB receptor in glomerulus. This effect seems to be mediated through
      intracellular Ca/calmodulin, but not through Ca influx via L-type Ca channel.
      Mesangial cells can be a source of NO coupled to ETB receptor activation in
      glomerulus. From these results, mesangial ETB receptor may work to counteract the
      vasoconstrictive effect of endothelin caused via ETA receptor in glomerulus.

PMID- 7509342
TI  - Induction of nitric oxide synthase by cyclic AMP in rat vascular smooth muscle
      cells.
AB  - By measurements of NO2-/NO3- (NOx) production and Northern blot analysis, we
      studied the effects of a membrane-permeable cAMP derivative, 8-bromo-cAMP, on the
      expression of inducible nitric oxide synthase (iNOS) gene and the synthesis of
      NOx in cultured rat vascular smooth muscle cells (VSMCs). 8-bromo-cAMP stimulated
      NOx production and increased steady-state levels of iNOS mRNA in rat VSMC in a
      time- and dose-dependent manner. NG-monomethyl-L-arginine, a NOS inhibitor,
      completely blocked the 8-bromo-cAMP-induced NOx production, whose effect was
      partially, but significantly reversed by an excess L-arginine, but not by D
      arginine. Compounds that increase intracellular cAMP levels (cholera toxin,
      forskolin, and 3-isobutyl-1-methylxanthine), all stimulated NOx production.
      Dexamethasone inhibited the stimulated NOx production, as well as the induction
      of iNOS mRNA by cAMP. Both actinomycin D and cycloheximide completely blocked the
      stimulated NOx production by cAMP. Actinomycin D abolished the cAMP-induced iNOS
      mRNA, whereas cycloheximide remarkably increased iNOS mRNA levels in the presence
      and absence of 8-bromo-cAMP (superinduction). Actinomycin D, but not
      dexamethasone, completely abolished the cycloheximide-induced iNOS mRNA. The half
      life of cAMP-induced iNOS mRNA was approximately 2 h, whereas no decay in the
      cycloheximide-induced iNOS mRNA was observed during 12 h. These results
      demonstrate that iNOS gene is upregulated by cAMP and the superinduction of iNOS
      mRNA is attributable to increased mRNA stability in rat VSMC.

PMID- 7509341
TI  - Elevated c-Src tyrosine kinase activity in premalignant epithelia of ulcerative
      colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with a
      high incidence of colon cancer. Dysplasia is a precursor to carcinoma and a
      predictor of malignant potential; epithelia containing high-grade or severe
      dysplasia is most likely to develop cancer. The cellular oncogene c-src and its
      viral homologue v-src (the transforming gene of Rous sarcoma virus) encode 60-kD
      cytoplasmic, membrane-associated protein tyrosine kinases. For the viral protein
      or transforming mutants of the cellular protein (Src), a close correlation exists
      between elevated tyrosine kinase activity and malignant transformation of cells.
      Previously, we and others observed elevated Src activity in sporadic colon
      carcinomas and benign adenomas at greatest risk for developing cancer (those with
      large size, villous architecture, and/or severe dysplasia). Here we report that
      Src activity and protein abundance are also elevated in neoplastic UC epithelia.
      Activity is highest in malignant and severely dysplastic epithelia, and 6-10-fold
      higher in mildly dysplastic than in nondysplastic epithelia. Thus, Src activity
      is elevated in premalignant UC epithelia, which is at greatest risk for
      developing cancer. The data suggest that activation of the src proto-oncogene is
      an early event in the genesis of UC colon cancer.

PMID- 7509345
TI  - Exercise-induced pulmonary vasoconstriction during combined blockade of nitric
      oxide synthase and beta adrenergic receptors.
AB  - We studied the effects of inhibition of nitric oxide (NO) (endothelium-derived
      relaxation factor) synthase in combination with alpha and beta adrenergic
      receptor blockade on pulmonary vascular tone during exercise. In paired studies,
      we exercised sheep on a treadmill at a speed of 4 mph, and measured blood flow
      and pressures across the pulmonary circulation with and without inhibition of NO
      synthase (N omega-nitro-L-arginine 20 mg/kg intravenous [i.v.]), alpha receptor
      blockade (phentolamine 5 mg i.v.), beta receptor blockade (propranolol 1 mg
      i.v.), and combined alpha and beta receptor blockade. Activation of both types of
      adrenergic receptors occurs with exercise, and because increased release in NO is
      hypothesized to occur during exercise, these studies were designed to determine
      the magnitude of effect and interactions of these competing dilator and
      constrictor influences. We found that inhibition of NO synthase raised pulmonary
      vascular resistance (PVR) at rest and that, although a reduction in PVR occurred
      with exercise from this new baseline, vasoconstriction persisted. Combined beta
      blockade and NO synthase inhibition unmasked unopposed alpha vasoconstriction;
      PVR rose at rest and continued to rise with exercise; and mean pulmonary arterial
      pressures approached very high levels, 43.8 +/- 4.4 cmH2O. Using a distal wedged
      pulmonary artery catheter technique, most of the vasoconstriction was found to be
      in vessels upstream from small pulmonary veins. During exercise in sheep there
      appears to be a high degree of alpha and beta adrenergic-mediated tone in the
      pulmonary circulation. Endogenous production of NO actively dilates pulmonary
      vessels at rest and opposes potent alpha-mediated pulmonary vasoconstriction
      during exercise.

PMID- 7509344
TI  - Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial
      growth factor augments revascularization in a rabbit ischemic hind limb model.
AB  - Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell
      specific mitogen. Previous studies have suggested that VEGF is a regulator of
      naturally occurring physiologic and pathologic angiogenesis. In this study we
      investigated the hypothesis that the angiogenic potential of VEGF is sufficient
      to constitute a therapeutic effect. The soluble 165-amino acid isoform of VEGF
      was administered as a single intra-arterial bolus to the internal iliac artery of
      rabbits in which the ipsilateral femoral artery was excised to induce severe,
      unilateral hind limb ischemia. Doses of 500-1,000 micrograms of VEGF produced
      statistically significant augmentation of collateral vessel development by
      angiography as well as the number of capillaries by histology; consequent
      amelioration of the hemodynamic deficit in the ischemic limb was significantly
      greater in animals receiving VEGF than in nontreated controls (calf blood
      pressure ratio, 0.75 +/- 0.14 vs. 0.48 +/- 0.19, P < 0.05). Serial angiograms
      disclosed progressive linear extension of the collateral artery of origin (stem
      artery) to the distal point of parent vessel (reentry artery) reconstitution in
      seven of nine VEGF-treated animals. These findings establish proof of principle
      for the concept that the angiogenic activity of VEGF is sufficiently potent to
      achieve therapeutic benefit. Such a strategy might ultimately be applicable to
      patients with severe limb ischemia secondary to arterial occlusive disease.

PMID- 7509346
TI  - Lipopolysaccharide (LPS)-binding protein and soluble CD14 function as accessory
      molecules for LPS-induced changes in endothelial barrier function, in vitro.
AB  - Bacterial LPS induces endothelial cell (EC) injury both in vivo and in vitro. We
      studied the effect of Escherichia coli 0111:B4 LPS on movement of 14C-BSA across
      bovine pulmonary artery EC monolayers. In the presence of serum, a 6-h LPS
      exposure augmented (P < 0.001) transendothelial 14C-BSA flux compared with the
      media control at concentrations > or = 0.5 ng/ml, and LPS (10 ng/ml) exposures of
      > or = 2-h increased (P < 0.005) the flux. In the absence of serum, LPS
      concentrations of up to 10 micrograms/ml failed to increase 14C-BSA flux at 6 h.
      The addition of 10% serum increased EC sensitivity to the LPS stimulus by >
      10,000-fold. LPS (10 ng/ml, 6 h) failed to increase 14C-BSA flux at serum
      concentrations < 0.5%, and maximum LPS-induced increments could be generated in
      the presence of > or = 2.5%. LPS-binding protein (LBP) and soluble CD14 (sCD14)
      could each satisfy this serum requirement; either anti-LBP or anti-CD14 antibody
      each totally blocked (P < 0.00005) the LPS-induced changes in endothelial barrier
      function. LPS-LBP had a more rapid onset than did LPS-sCD14. The LPS effect in
      the presence of both LBP and sCD14 exceeded the effect in the presence of either
      protein alone. These data suggest that LBP and sCD14 each independently functions
      as an accessory molecule for LPS presentation to the non-CD14-bearing endothelial
      surface. However, in the presence of serum both molecules are required.

PMID- 7509347
TI  - Expression of the cystic fibrosis gene in adult human lung.
AB  - Critical to an understanding of the pulmonary disease in cystic fibrosis (CF) and
      the development of effective gene therapies is a definition of the distribution
      and regulation of CF gene expression in adult human lung. Previous studies have
      detected the product of the CF gene, the CF transmembrane conductance regulator
      (CFTR), in submucosal glands of human bronchi. In this report, we have
      characterized the distribution of CFTR RNA and protein in the distal airway and
      alveoli of human lungs. Samples from eight human lungs were analyzed for CFTR
      expression by in situ hybridization and immunocytochemistry. CFTR was detected in
      a subpopulation of epithelial cells at every level of the distal lung, including
      proximal, terminal, and respiratory bronchioles, and the alveoli. However, there
      was substantial variation in the level of CFTR expression between samples. In
      bronchioles, CFTR protein localized to the apical plasma membrane and was found
      primarily in a subpopulation of nonciliated cells. CFTR was expressed in the same
      distribution as the Clara cell marker CC10 in proximal bronchioles, however,
      expression was discordant in the more distal bronchioles and alveoli where CC10
      was not detected. These studies suggest that epithelial cells of the distal lung
      may play a primary role in the pathogenesis of CF as well as expand the spectrum
      of target cells that should be considered in the development of gene therapies.

PMID- 7509349
TI  - DNA variation in the genes of the Na,K-adenosine triphosphatase and its relation
      with resting metabolic rate, respiratory quotient, and body fat.
AB  - The aim of this study was to investigate in 261 subjects from 58 families the
      association between DNA variation at the genes coding for the Na,K-ATPase
      peptides and resting metabolic rate (RMR), respiratory quotient (RQ), and percent
      body fat (%FAT). Five restriction fragment length polymorphisms (RFLP) at three
      Na,K-ATPase genes were determined: one at the alpha 1 locus (BglII), and two at
      the beta locus (beta MspI and beta PvuII). Haplotypes were determined from the
      two variable sites of the alpha 2 gene (alpha 2 haplotypes) and the beta gene
      (beta haplotypes). There was a strong trend for %FAT to be related to the RFLP
      generated by BglII at the alpha 2 exons 21-22 in males (P = 0.06) and females (P
      = 0.05). RQ was (a) associated with the BglII RFLP at the alpha 2 exon 1 (P =
      0.02) and with the alpha 2 8.0 kb/4.3 kb haplotype (P = 0.04) and (b) linked with
      the beta gene MspI marker (P = 0.04) and with the beta 5.3 kb/5.1 kb haplotype (P
      = 0.008) based on sib-pair analysis. The present study suggests that the genes
      encoding Na,K-ATPase may be associated or linked with RQ and perhaps with %FAT
      but not with RMR.

PMID- 7509348
TI  - Angiotensin II induces delayed mitogenesis and cellular proliferation in rat
      aortic smooth muscle cells. Correlation with the expression of specific
      endogenous growth factors and reversal by suramin.
AB  - By means of a rat aortic smooth muscle (RASM) cell culture model, the effects of
      angiotensin II (AII) on early proto-oncogene gene expression, DNA synthesis, and
      cell proliferation were measured and compared to known mitogens. In 24-h [3H]
      thymidine incorporation assays, AII was found to be a weak mitogen when compared
      to potent mitogens such as fetal bovine serum and platelet-derived growth factor
      (PDGF). In contrast, when assays were carried out for 48 h, AII induced a
      significant dose-dependent stimulation of DNA synthesis, which more than doubled
      at 3 nM AII, and was maximal (five- to eightfold above control) at 100 nM AII.
      Treatment of cells with the AII type 1 receptor antagonist losartan inhibited the
      mitogenic effects of AII. AII also stimulated smooth muscle cell proliferation,
      as indicated by an absolute increase in cell number after AII stimulation of RASM
      cells for 5 d. AII stimulation of RASM cell growth correlated with the increased
      expression of specific endogenous growth factors, including transforming growth
      factor beta 1 (TGF-beta 1) and PDGF A-chain. However, addition of either PDGF- or
      TGF-beta 1-neutralizing antibodies failed to significantly reduce the delayed
      mitogenic effects induced by AII. In contrast, we found that AII-stimulated
      mitogenesis could be inhibited in a dose-dependent manner by the growth factor
      inhibitor drug suramin. Taken together, our results indicate that enhanced
      endogenous growth factor expression may represent the direct mechanism by which
      AII promotes smooth muscle cell growth in some vascular hyperproliferative
      diseases.

PMID- 7509351
TI  - Lysophosphatidylcholine transcriptionally induces growth factor gene expression
      in cultured human endothelial cells.
AB  - Lysophosphatidylcholine (lyso-PC) is a major phospholipid component of
      atherogenic lipoproteins (e.g., oxidized LDL and beta-VLDL) and also can be
      generated through the action of leukocyte-secreted phospholipase A2 at sites of
      inflammation. We have previously reported that lyso-PC can activate cultured
      endothelia, resulting in the selective upregulation of adhesion molecules, such
      as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. In
      this study, we have found that lyso-PC increased steady state mRNA levels for two
      smooth muscle/fibroblast-directed growth factors, the A and B chains of PDGF and
      heparin-binding EGF-like protein (HB-EGF), in cultured human endothelial cells.
      Lyso-PC did not upregulate the expression of certain other inducible endothelial
      genes, including E-selectin, IL-8, or monocyte chemoattractant protein-1 in the
      same cells, in contrast to the coordinate pattern of activation typically
      observed with other stimuli, such as TNF alpha, bacterial endotoxin, or PMA.
      Nuclear runoff assays documented an increased transcriptional rate for the HB-EGF
      gene in lyso-PC-treated cells. Northern blot analyses, after actinomycin D
      treatment, further indicated that the increased amounts of mRNA for HB-EGF, PDGF
      A and B chains, and intercellular adhesion molecule-1 were not dependent upon
      message stabilization. We conclude that lyso-PC can induce growth factor gene
      expression in cultured endothelial cells and thus may contribute to the migration
      and proliferation of smooth muscle cells and fibroblasts in various response-to
      injury settings in vivo.

PMID- 7509350
TI  - Rheumatoid factors from the peripheral blood of two patients with rheumatoid
      arthritis are genetically heterogeneous and somatically mutated.
AB  - We report the DNA sequences of the heavy and light chain immunoglobulin genes of
      11 monoclonal rheumatoid factor (RF)-secreting lines derived from the peripheral
      blood of two patients with rheumatoid arthritis (RA). It is evident from
      immunogenetic analysis of these lines that RA-associated RF activity can arise
      from a wide variety of heavy and light chain genes and gene combinations.
      Although the RF response from our two patients shows a bias in gene usage toward
      those genes used to encode monoclonal RF, particularly VkIII, relatively few of
      these RFs are reactive with the monoclonal antiidiotypes 6B6.6 and 17.109 that
      define VkIII germline-encoded light chains and the loss of this idiotypic
      reactivity is clearly related to somatic mutation. Finally, RFs derived from
      peripheral blood of RA patients show a similar heterogeneity of epitope binding
      to Fc as that seen for synovium-derived RF and some are clearly different in
      binding specificity from the restricted RF population found in patients with B
      cell malignancies. Somatic mutations as well as different VH/VL combinations
      contribute to the heterogeneity in the binding patterns of these RA-derived RF.

PMID- 7509354
TI  - Dermatofibrosarcoma protuberans expresses CD34.

PMID- 7509353
TI  - Characterization of cultured nail matrix cells.
AB  - BACKGROUND: Cultures of epidermal cells are commonly used to study skin biology
      and differentiation. Recently a method to culture nail matrix cells has been
      established. OBJECTIVE: We report the biologic characteristics of nail matrix
      cells in vitro compared with those of epidermal keratinocytes. METHODS: Human
      nail matrix cells were isolated and cultured in defined medium. Electron
      microscopic examination, growth rate, integrin expression and keratin synthesis
      pattern were evaluated. In addition, the cells were cultured in serum-containing
      medium. RESULTS: Nail matrix cells appear to be larger than human epidermal
      keratinocytes and, at the ultrastructural level, they contain a higher
      euchromatin/heterochromatin ratio and a lower nucleus/cytoplasm ratio and have a
      higher growth rate. The synthesis of "hard" keratins was detected at all calcium
      concentrations. Immunofluorescence analyses showed the expression of alpha 2,
      alpha 3, and alpha 6 integrin subunits. When cultured in serum-containing medium,
      nail matrix cells produced an outgrowth of epithelium and a spontaneous migration
      phenomenon associated with a tendency to stratify in a semilunar area that
      resembles the architecture of the nail matrix. The pluristratified epithelium
      showed characteristic markers of nail differentiation. CONCLUSION: Culture of
      nail matrix cells may represent a useful model to study the biologic properties
      of nail structure, alterations in some nail diseases and the effects of drugs.

PMID- 7509352
TI  - Ontogeny of GABAA receptor subunit mRNAs in rat spinal cord and dorsal root
      ganglia.
AB  - Relatively little is known about the development of GABAA receptor subunits and
      their gene expression in mammalian spinal cord. The expression of mRNAs encoding
      13 GABAA receptor subunits (alpha 1-6, beta 1-3, gamma 1-3, and delta) in
      embryonic, postnatal, and adult rat spinal cord and dorsal root ganglia (DRG)
      cells were studied by in situ hybridization and reverse transcription-polymerase
      chain reaction (RT-PCR) analysis. Both techniques revealed the presence of all
      subunit mRNAs originally found in the rat brain, except for alpha 6, which was
      not detectable, and delta, which was weakly detected only by RT-PCR. Two
      anatomically distinctive sets of subunit mRNAs were found by in situ
      hybridization within the ventricular zone (VZ) and mantle zone (MZ). The trio of
      alpha 4, beta 1, and gamma 1 subunit mRNAs emerged exclusively in neuroepithelial
      cells at embryonic day 13 (E13) and remained detectable in the VZ until E17. In
      the MZ, beta 3 subunit mRNA was first detected at E12, while alpha 2, alpha 3,
      alpha 5, beta 2, gamma 2, and gamma 3 transcripts appeared at E13. Expressions of
      the subunit mRNAs in the MZ rapidly increased and expanded in a ventrodorsal
      sequence from motoneurons to dorsal horn neurons before reaching a peak in the
      late embryonic/early postnatal period. The mRNA expressions declined during
      postnatal development, by region-selective depletion, with alpha 4, alpha 5, beta
      1, beta 2, gamma 1, and gamma 3 subunit mRNAs becoming barely detectable. In
      contrast, alpha 2, alpha 3, beta 3, and gamma 2 transcripts persisted into
      adulthood with distinct anatomical distributions. RT-PCR analysis revealed unique
      developmental patterns in the intensities of PCR products, most of which were in
      good agreement with developmental changes in the densities of hybridized mRNA
      signals. However, RT-PCR amplified minute amounts of mRNAs for alpha 1, alpha 4,
      alpha 5, beta 1, beta 2, gamma 1, gamma 3, and delta subunits in adults, which
      were not found in film autoradiograms, but could be detected in a few grain
      positive cells in emulsion-dipped sections. DRG cells expressed alpha 2, alpha 3,
      alpha 5, beta 2, beta 3, and gamma 2 subunit mRNAs during embryogenesis but only
      alpha 2, beta 3, and gamma 2 subunit mRNAs were reliably detected in the
      adult.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7509356
TI  - The acute effects of pancreaticopyelostomy on the pancreas and kidney. A
      preliminary study.
AB  - A modified canine pancreaticopyelostomy model with an intact kidney was
      constructed. The effects of this procedure on the pancreas and kidney were
      examined in five dogs by monitoring the serum and urine levels of pH,
      bicarbonate, chloride, glucose, urea, creatinine and amylase in 24-h periods for
      up to 72 h. The contralateral kidney served as controls. The pancreas and kidney
      were removed and examined under light microscopy after the animals were
      sacrificed. Both of the organs had maintained their normal histological
      architecture. The serum and urine glucose levels were consistent with a normal
      response after the initial elevation immediately following the surgical trauma.
      The urine urea concentrations from both kidneys were similar, as were the
      creatinine excretion trends throughout the 72 h, except for a significant rise in
      the creatinine excretion on the pancreaticopyelostomy side at 24 h. The pH,
      bicarbonate, chloride, and amylase values revealed a normal and functioning
      exocrine pancreas. It is concluded from this preliminary study that
      pancreaticopyelostomy with an intact kidney does not have acute adverse effects,
      either on the pancreas or on the kidney. This procedure may be an alternative
      method for pancreatic exocrine drainage if similar results are obtained in
      chronic models.

PMID- 7509355
TI  - Predicting mortality after myocardial infarction from the response of RR
      variability to antiarrhythmic drug therapy.
AB  - OBJECTIVES: This study was designed to test the hypothesis that antiarrhythmic
      drugs that decrease RR variability will predict all-cause mortality during follow
      up after myocardial infarction. BACKGROUND: RR variability, a noninvasive
      indicator of autonomic nervous system activity, predicts death after acute
      myocardial infarction independently of other risk predictors and changes
      substantially in response to some drugs. A previous study in patients with
      chronic heart disease and frequent ventricular premature complexes reported that
      flecainide decreased vagal modulation of RR intervals but amiodarone did not. The
      investigators of that study speculated that changes in RR variability during
      antiarrhythmic drug therapy predict an increased mortality rate during long-term
      drug treatment. To explore this hypothesis further, we compared the effects of
      encainide and flecainide, which increase long-term mortality substantially, on RR
      variability with the effects of placebo and moricizine, which have no significant
      effect on mortality during long-term treatment of unsustained ventricular
      arrhythmias after myocardial infarction. METHODS: The 24-h power spectral density
      was computed from the baseline electrocardiographic recordings and drug
      evaluation tapes, and six frequency domain measures of RR variability were
      calculated: ultra-low frequency (< 0.0033 Hz), very low frequency (0.0033 to <
      0.04 Hz), low frequency (0.04 to < 0.15 Hz) and high frequency power (0.15 to <
      0.40 Hz), plus total power (< 0.40 Hz) and the ratio of low to high frequency
      power. Changes in power spectral measures were related to drug treatment and to
      mortality. RESULTS: In the placebo group, values for RR interval and RR
      variability increased because of recovery from the effects of acute myocardial
      infarction. Contrasting placebo treatment with all three active antiarrhythmic
      drug treatments taken together showed that of all the measures of RR variability,
      only NN50, pNN50 and low frequency power changed significantly during drug
      treatment (Bonferroni adjusted p value < 0.025); these variables all decreased
      during drug therapy. Contrasting encainide and flecainide with moricizine, we
      found that the encainide and flecainide groups taken together showed a larger
      decrease in dLF than moricizine, but the difference was of borderline
      significance (Bonferroni adjusted p value < 0.08). Survival was significantly
      worse in the groups treated with encainide and flecainide than in the groups
      treated with placebo or moricizine (relative risk > 2.0, adjusted p < 0.05). The
      antiarrhythmic drug-induced change in measures of RR variability was not a
      significant predictor of all-cause mortality during a year of follow-up after
      myocardial infarction. CONCLUSIONS: Encainide, flecainide and moricizine all
      caused a decrease in RR variability in patients studied approximately 1 month
      after acute myocardial infarction. Encainide and flecainide caused a significant
      increase in mortality rates; placebo and moricizine did not. Baseline
      measurements of RR variability also predicted all-cause mortality after
      myocardial infarction. The decrease in RR variability produced by the three
      antiarrhythmic drugs did not predict mortality during follow-up.

PMID- 7509357
TI  - Helicobacter pylori: a comparison of CLO test and Giemsa's stain with culture in
      dyspeptic patients.
AB  - The prevalence of H.pylori in Thailand is high compared with Western countries
      and is the same as in China. We suggest either rapid urease test (CLO test) or
      Giemsa stain to be a rapid, reliable and convenient detection method for H.pylori
      and is also suitable for use in follow-up studies by gastroenterologists.

PMID- 7509358
TI  - Regulation of the expression of the hematopoietic stem cell antigen CD34: role of
      c-myb.
AB  - The CD34 antigen defines a subset of hematopoietic progenitor cells with self
      renewal capacity and the ability to reconstitute hematopoiesis in irradiated
      primates and marrow-ablated humans, but its function remains unknown. The c-myb
      protooncogene plays a fundamental role in hematopoiesis, most likely via its
      transcriptional regulator function. We report that c-myb protein transactivates
      the CD34 promoter via specific interaction with multiple Myb binding sites in the
      5' flanking region of the gene and induces expression of the endogenous CD34 mRNA
      in rodent fibroblasts. Also, constitutive expression of c-myb in CD34-negative
      human glioblastoma cells induces expression of CD34 mRNA and synthesis of the
      surface membrane antigen. These data directly demonstrate that c-myb regulates
      the expression of the hematopoietic stem cell antigen CD34 and raise the
      possibility that c-myb regulates hematopoiesis inducing a cascade of
      differentiation-related events.

PMID- 7509360
TI  - Stimulation of CD28 triggers an association between CD28 and phosphatidylinositol
      3-kinase in Jurkat T cells.
AB  - The T cell surface molecule CD28 can provide costimulatory signals that permit
      the full activation of T cells. Here we demonstrate that stimulation of CD28,
      either by B7, its natural ligand, or by the anti-CD28 monoclonal antibody 9.3,
      induces an association between CD28 and phosphatidylinositol 3-kinase (PI3-K) in
      Jurkat T cells, raising the possibility that an interaction with PI3-K
      contributes to CD28-mediated signaling. To examine the mechanism of the
      association, we synthesized tyrosine-phosphorylated oligopeptides corresponding
      to each of the four tyrosines in the CD28 cytoplasmic domain. When added to
      lysates of B7-stimulated Jurkat cells, the oligopeptide corresponding to Tyr 173
      inhibits the coimmunoprecipitation of PI3-K with CD28; the other oligopeptides
      have no effect. Tyr 173 is contained within the sequence YMNM, a motif that is
      also found in the platelet-derived growth factor receptor and that, when
      phosphorylated, forms a high affinity binding site for the p85 subunit of PI3-K.
      These observations suggest that phosphorylation of Tyr 173 may mediate the
      interaction between CD28 and PI3-K. However, because CD28 is not known to be
      phosphorylated, it remains possible that CD28 interacts with PI3-K through a
      mechanism independent of tyrosine phosphorylation.

PMID- 7509361
TI  - B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers
      correlated with poor affinity maturation and class switching despite normal
      priming of CD4+ T cells.
AB  - This report outlines the B cell phenotype of transgenic mice that overexpresses
      the mouse CTLA-4-human gamma 1 (mCTLA4-H gamma 1) protein. Despite the fact that
      these mice prime CD4+ T cells (Ronchese, F., B. Housemann, S. Hubele, and P.
      Lane. 1994. J. Exp. Med. 179:809), antibody responses to T-dependent antigens are
      severely impaired. In contrast, T-independent responses are normal which suggests
      mCTLA4-H gamma 1 does not act directly on B cells, but acts indirectly by
      impairing T cell help. The impaired antibody defect is associated with impaired
      class switching, with low total immunoglobulin (Ig)G and antigen-specific IgG
      responses, and an absence of germinal center formation in spleen and lymph nodes
      but not gut-associated tissues. The defective germinal center formation is
      associated with a reduction in the degree of somatic mutation in hybridomas made
      from transgenic mice in comparison with those made from normal mice. It seems
      likely that mCTLA4-H gamma 1 exerts its effect by blocking an interaction between
      T and B cells that induce T cell help for B cells.

PMID- 7509363
TI  - Induction of tumor necrosis factor alpha production by human hepatocytes in
      chronic viral hepatitis.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine that has an
      important role in the pathogenesis of inflammation, cachexia, and septic shock.
      Although TNF-alpha is mainly produced by macrophages, there is evidence regarding
      TNF-alpha production by cells that are not derived from bone marrow. TNF-alpha
      production by normal and inflamed human liver was assessed at both mRNA and
      protein levels. Using a wide panel of novel anti-TNF-alpha monoclonal antibodies
      and a specific polyclonal antiserum, TNF-alpha immunoreactivity was found in
      hepatocytes from patients chronically infected with either hepatitis B virus
      (HBV) or hepatitis C virus. Minimal TNF-alpha immunoreactivity was detected in
      the mononuclear cell infiltrate and Kupffer cells. In situ hybridization
      experiments using a TNF-alpha RNA probe showed a significant expression of TNF
      alpha mRNA in hepatocytes, Kupffer cells, and some infiltrating mononuclear
      cells. By contrast, TNF-alpha was detected at low levels in liver biopsies from
      normal individuals or patients with alcoholic liver disease and low expression of
      TNF-alpha mRNA was observed in these specimens. Transfection of HepG2
      hepatoblastoma cells with either HBV genome or HBV X gene resulted in induction
      of TNF-alpha expression. Our results demonstrate that viral infection induces,
      both in vivo and in vitro, TNF-alpha production in hepatocytes, and indicate that
      the HBV X protein may regulate the expression of this cytokine. These findings
      suggest that TNF-alpha may have an important role in human liver diseases induced
      by viruses.

PMID- 7509362
TI  - Stimulation of all epithelial elements during skin regeneration by keratinocyte
      growth factor.
AB  - Keratinocyte growth factor (KGF), a recently discovered 18.9 kD member of the
      fibroblast growth factor family has been shown to selectively induce keratinocyte
      proliferation and differentiation in tissue culture. To explore its potential
      stimulating keratinocyte growth and differentiation in vivo, we analyzed for the
      influence of KGF on epithelial derived elements within a wound created through
      the cartilage on the rabbit ear. KGF accelerated reepithelialization (p = 0.004)
      and increased the thickness of the epithelium (p = 0.0005) when 4-40
      micrograms/cm2 recombinant KGF was added at the time of wounding. The
      regenerating epidermis showed normal differentiation as detected by cytokeratin
      immunostaining. Remarkably, however, KGF stimulated proliferation and
      differentiation of early progenitor cells within hair follicles and sebaceous
      glands in the wound bed and adjacent dermis. There was a transient but highly
      significant increase in specific labeling of cycling cells in both basal and
      suprabasal layers that extended into the spinous layer of the regenerating
      epidermis. As an indication of specificity, the inflammatory cells and
      fibroblasts within the wound were not influenced by KGF. The results indicate
      that KGF is unique in its ability to accelerate reepithelialization and dermal
      regeneration by targeting multiple epithelial elements within the skin. These
      results suggest that KGF may induce specific epithelial progenitor cell lineages
      within the skin to proliferate and differentiate, and thus may be a critical
      determinant of regeneration of skin. Furthermore, these findings illustrate the
      potential capacity of this system to analyze epithelial differentiation programs
      and disorders of epidermis, dermal glandular elements, and hair follicles.

PMID- 7509359
TI  - Identification of amino acids at the junction of exons 3 and 7 that are used for
      the generation of glycosylation-related human CD45RO and CD45RO-like antigen
      specificities.
AB  - The CD45 transmembrane protein tyrosine phosphatase plays an essential role in
      lymphocyte activation. In humans, CD45 is composed of five isoforms that are
      generated by alternative splicing of three exons of a common precursor mRNA.
      Expression of the smallest molecular mass 180-kD CD45 isoform (CD45-O) results
      from splicing out of exons 4(A), 5(B), and 6(C), which encode peptide regions
      near the NH2 terminus, and is regulated during T cell maturation and activation.
      Two monoclonal antibodies (mAb), UCHL1 (anti-CD45RO) and A6 (anti-CD45RO-like),
      were studied that selectively bind to murine transfectant cells expressing the
      human CD45-O isoform. The anti-CD45RO-like A6 mAb, but not the anti-CD45RO UCHL1
      mAb, also weakly reacted with transfectant cells expressing the human CD45
      isoforms that contained exons 4 and 5(AB), or exon 5(B) encoded sequences. The
      structural basis of the antigen specificities of these two different human anti
      CD45RO mAbs was investigated at the molecular level by using potential
      glycosylation-defective CD45-O isoform variants containing amino acid
      substitutions at the junction of exons 3 and 7. Replacement of the threonine
      residue at position 8 (last amino acid encoded in exon 3 and a putative O-linked
      carbohydrate anchorage site) by an alanine, completely abrogated the reactivity
      of the UCHL1 mAb, but did not affect that of the A6 mAb. Conversely, replacement
      of either the asparagine at position 174 or the serine at position 176 (the first
      two putative carbohydrate anchorage sites in exon 7) by alanine, abrogated the
      reactivity of the A6 mAb, but not that of the UCHL1 mAb. Both the UCHL1 and A6
      epitopes were dependent on the presence of O-linked carbohydrates; and the UCHL1,
      but not the A6 epitope, was dependent on the presence of sialic acid. These
      results demonstrate a pivotal role for the amino acids encoded at the junction of
      exons 3 and 7 for the generation of glycosylation-related CD45RO epitopes that
      are expressed in a cell lineage- and activation-regulated fashion.

PMID- 7509364
TI  - Purification and characterization of the Fas-ligand that induces apoptosis.
AB  - Fas is a 45-kD cell surface protein belonging to the tumor necrosis factor/nerve
      growth factor receptor family, and transduces the signal for apoptosis. The
      cytotoxic T lymphocyte (CTL) hybridoma, PC60-d10S requires the presence of Fas on
      target cells to induce cytolysis in target cells. This CTL cell line was weakly
      but specifically stained by a chimeric protein that consisted of the
      extracellular domain of mouse Fas and the Fc portion of human immunoglobulin G1
      (mFas-Fc). Moreover, mFas-Fc inhibited the cytotoxic activity of PC60-d10S.
      Sublines of d10S that were stained intensively by mFas-Fc were isolated by
      repetitive fluorescence-activated cell sorter sorting. A cell-surface protein of
      about 40 kD was specifically precipitated by mFas-Fc from the lysates of these
      sublines. This protein was homogeneously purified by sequential affinity
      chromatographies using mFas-Fc and concanavalin A beads. The purified protein
      exhibited cytotoxic activity against cells expressing Fas but not to the cells
      which do not express Fas. These results indicated that the 40-kD membrane
      glycoprotein expressed on PC60-d10S cells is the Fas-ligand that induces the
      apoptotic signal by binding to Fas.

PMID- 7509367
TI  - Expression of a foreign epitope on the surface of the adenovirus hexon.
AB  - To present short protein sequences to the host immune system a foreign epitope
      has been expressed on the surface of the adenovirus virion as part of the hexon.
      As the trimeric hexon constitutes 240 out of the 252 capsomers of the virus, the
      foreign epitope is repeated 720 times on the virion surface. An eight amino acid
      sequence from the major antigenic site in the VP1 capsid protein of poliovirus
      type 3 was engineered into two regions of the adenovirus type 2 hexon. The two
      loop regions chosen to accommodate the foreign sequences are exposed on the
      surface of the virion, show sequence variation between serotypes and are the
      sites of interaction with neutralizing antibodies. Virus with substitutions in
      loop I had wild-type growth characteristics, whereas virus with substitutions in
      loop II grew poorly. Adenoviruses with poliovirus sequences in loop I were
      recognized and efficiently neutralized by antisera specific for the poliovirus
      sequence; an antiserum raised against the adenovirus with the poliovirus insert
      specifically recognized the VP1 capsid protein of poliovirus type 3. It is
      therefore feasible to alter the surface properties of the adenovirus virion and
      in doing so to manipulate the immune response to this virus.

PMID- 7509366
TI  - Increased frequency of interleukin 2-responsive T cells specific for myelin basic
      protein and proteolipid protein in peripheral blood and cerebrospinal fluid of
      patients with multiple sclerosis.
AB  - Equal numbers of CD4+ T cells recognizing myelin basic protein (MBP) and
      proteolipid protein (PLP) are found in the circulation of normal individuals and
      multiple sclerosis (MS) patients. We hypothesized that if myelin-reactive T cells
      are critical for the pathogenesis of MS, they would exist in a different state of
      activation as compared with myelin-reactive T cells cloned from the blood of
      normal individuals. This was investigated in a total of 62 subjects with
      definitive MS. While there were no differences in the frequencies of MBP- and PLP
      reactive T cells after primary antigen stimulation, the frequency of MBP or PLP
      but not tetanus toxoid-reactive T cells generated after primary recombinant
      interleukin (rIL-2) stimulation was significantly higher in MS patients as
      compared with control individuals. Primary rIL-2-stimulated MBP-reactive T cell
      lines were CD4+ and recognized MBP epitopes 84-102 and 143-168 similar to MBP
      reactive T cell lines generated with primary MBP stimulation. In the
      cerebrospinal fluid (CSF) of MS patients, MBP-reactive T cells generated with
      primary rIL-2 stimulation accounted for 7% of the IL-2-responsive cells, greater
      than 10-fold higher than paired blood samples, and these T cells also selectively
      recognized MBP peptides 84-102 and 143-168. In striking contrast, MBP-reactive T
      cells were not detected in CSF obtained from patients with other neurologic
      diseases. These results provide definitive in vitro evidence of an absolute
      difference in the activation state of myelin-reactive T cells in the central
      nervous system of patients with MS and provide evidence of a pathogenic role of
      autoreactive T cells in the disease.

PMID- 7509368
TI  - Sequence and structural analysis of murine adenovirus type 1 hexon.
AB  - The genomic region encoding the major capsid protein (hexon) of murine adenovirus
      type 1 (MAV-1) has been isolated and sequenced. The sequence predicts a 908
      residue MAV-1 hexon protein and is flanked by a portion of the upstream pVI gene
      and the downstream endoproteinase gene. The order of these genes and their
      location in the middle of the genome are the same as those found in other
      adenoviruses sequenced to date. Multiple sequence alignment with the other five
      known hexon protein sequences reveals an overall residue identity of 51% and
      residue conservation of 66%. In comparison with human adenovirus type 2 (Ad2),
      MAV-1 hexon has major deletions between residues 141 to 170, 270 to 284 and 446
      to 455. Since these regions in the Ad2 hexon are partially exposed on the outer
      surface of the virion, they may represent type-specific antigenic determinants.
      The MAV-1 hexon sequence has been modelled using the known three-dimensional
      structure of the Ad2 hexon. The variable regions in which the mutations,
      deletions and insertions occur are located in the l1 and l2 loops of the molecule
      that form the protruding hexon towers on the external surface of the virion.

PMID- 7509365
TI  - Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig
      model of allergic airways inflammation.
AB  - Eosinophil accumulation is a prominent feature of allergic inflammatory
      reactions, such as those occurring in the lung of the allergic asthmatic, but the
      endogenous chemoattractants involved have not been identified. We have
      investigated this in an established model of allergic inflammation, using in vivo
      systems both to generate and assay relevant activity. Bronchoalveolar lavage
      (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol
      challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized
      assay guinea pigs and the accumulation of intravenously injected 111In
      eosinophils was measured. Activity was detected at 30 min after allergen
      challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL
      fluid was purified using high performance liquid chromatography techniques in
      conjunction with the skin assay. Microsequencing revealed a novel protein from
      the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The
      protein, "eotaxin," exhibits homology of 53% with human MCP-1, 44% with guinea
      pig MCP-1, 31% with human MIP-1 alpha, and 26% with human RANTES. Laser
      desorption time of flight mass analysis gave four different signals (8.15, 8.38,
      8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was
      highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2 pmol
      dose in the skin, but did not induce significant 111In-neutrophil accumulation.
      Eotaxin was a potent stimulator of both guinea pig and human eosinophils in
      vitro. Human recombinant RANTES, MIP-1 alpha, and MCP-1 were all inactive in
      inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was
      obtained that eotaxin shares a binding site with RANTES on guinea pig
      eosinophils. This is the first description of a potent eosinophil chemoattractant
      cytokine generated in vivo and suggests the possibility that similar molecules
      may be important in the human asthmatic lung.

PMID- 7509370
TI  - Zidovudine treatment results in the selection of human immunodeficiency virus
      type 1 variants whose genotypes confer increasing levels of drug resistance.
AB  - High level resistance to 3'-azido-3'-deoxythymidine (AZT, zidovudine or Retrovir)
      is conferred by the presence of four or five mutations (Met-41-->Leu; Asp-67-
      >Asn; Lys-70-->Arg; Thr-215-->Tyr or Phe; Lys-219-->Gln) in the human
      immunodeficiency virus (HIV) reverse transcriptase. The order of appearance of
      these five mutations in asymptomatic patients during therapy has been studied.
      This has enabled us to propose a model for the acquisition of zidovudine
      resistance mutations during the treatment of high-risk asymptomatic HIV-infected
      individuals. A consistent acquisition pattern of mutations at codons 41, 70 and
      215 was observed in 17 individuals. Complex mixtures of HIV species containing
      different combinations of single and linked double resistance mutations were
      present early in zidovudine therapy in isolates from two patients studied in
      detail. From these mixtures the linked Leu-41/Tyr-215 genotype outgrew all others
      initially. The development of each new virus population is likely to be mediated
      primarily by the increase in the level of drug resistance rather than changes in
      the growth kinetics of the virus. This leads us to conclude that one major
      driving force in the outgrowth of different mutant viruses is the selective
      advantage conferred by higher levels of drug resistance.

PMID- 7509369
TI  - Immune response to human papillomavirus type 16 E6 gene in a live vaccinia
      vector.
AB  - Immunization of mice with a recombinant vaccinia virus expressing the human
      papillomavirus type 16 (HPV-16) E6 gene elicits specific antibody, proliferative
      and cytotoxic T lymphocyte responses. T and B cell epitopes were mapped by using
      synthetic peptides. This study provides the background to future investigation
      aimed at developing prophylactic and therapeutic vaccines against HPV-16
      infection and cervical cancer.

PMID- 7509371
TI  - An empirical study of Freud's penis-baby equation.
AB  - One hypothesis of traditional psychoanalytic theory holds that a cardinal aspect
      of the "natural" development of femininity involves the woman's substitution of
      the wish for a baby in place of her original wish for a penis. The current study
      modified and extended earlier research examining the validity of Freud's this
      "penis-baby" theory. College-aged women and men were presented with either
      subliminal or supraliminal auditory messages concerned with either pregnancy or
      penetration themes. Subjects' written responses to Holtzman ink-blots, obtained
      both before and after exposure to an auditory message, were content-coded for
      phallic imagery and sexual imagery. Consistent with Freud's speculations about
      the phallic significance of pregnancy for women, female subjects who were exposed
      to the subliminal pregnancy message produced significantly more phallic imagery
      responses to ink-blots than did women in any of the other experimental conditions
      (p < .01). The phallic imagery production of males did not vary significantly as
      a function of message condition. Implications of these findings are discussed in
      the context of modern revisions to Freud's psychology of women and the current
      psychoanalytic conceptualization of penis envy as a highly condensed mental
      product with many layers of meaning.

PMID- 7509372
TI  - Amino acid residues 226-240 of tau, which encompass the first Lys-Ser-Pro site of
      tau, are partially phosphorylated in Alzheimer paired helical filament-tau.
AB  - A synthetic peptide corresponding to residues 226-240 (E9 peptide) of human tau,
      which contains an Lys-Ser-Pro motif, was used to raise a polyclonal antibody. The
      antibody, E9, was 10-fold less reactive with phospho-E9 peptide than with native
      E9 peptide. E9 antibody was used to study the extent of phosphorylation in a
      modified form of tau (PHF-tau) that is found in Alzheimer's disease brain and is
      incorporated into paired helical filaments (PHFs). E9 immunolabeled Alzheimer's
      disease neurofibrillary tangles and abnormal neurites in brain sections
      intensely, with increased immunoreactivity detected after pretreatment of
      sections with phosphatase. On immunoblots and ELISA, E9 reacted with PHF-tau and
      recombinant human tau but not with the high and middle molecular weight
      neurofilament proteins. Phosphatase treatment of PHF-tau improved the E9
      immunoreactivity by 30-50%. Dephosphorylated high but not middle molecular weight
      neurofilament protein became reactive with E9. These results indicate that < 50%
      of the PHF-tau is phosphorylated in the subregion corresponding to residues 226
      240 of tau and suggest that the phosphorylation of this region may not be
      essential for PHF formation.

PMID- 7509373
TI  - Regulation of ganglioside composition and synthesis is different in developing
      chick retinal pigment epithelium and neural retina.
AB  - We examined the immunocytochemical expression of GM3 and GD3 in 3-day-old chick
      embryo retinal pigment epithelium (RPE) and neural retina (NR). We also compared
      the composition of gangliosides and the activities of key ganglioside
      glycosyltransferases of the RPE and NR of 8-, 12-, and 15-day old embryos. The
      immunocytochemical studies in 3-day-old embryos showed heavy expression of GM3
      and GD3 at the inner and outer layers of the optic vesicle that are the
      precursors of the RPE and NR, respectively. The compositional and enzymatic
      studies showed pronounced differences between RPE and NR of 8-day and older
      embryos. HPTLC showed that at 8 days the major species were GM3 and GD3 in RPE
      and GD3 and GT3 in NR. As development proceeded, GD3 decreased in both tissues,
      GM3 became the major ganglioside in RPE, and ganglio-series gangliosides (mainly
      GD1a) became the major species in NR. At 15 days the major species were GD1a in
      NR and GM3 in RPE. Enzyme determinations showed that whereas in RPE from 12-day
      old embryos GM2 synthase was under the limit of detection and GD3 synthase
      activity was about sixfold lower than GM3 synthase, in NR the activities of GM3
      and GD3 synthases were similar and both six- to ninefold lower than GM2 synthase.
      These results evidence a markedly different modulation of the ganglioside
      glycosylating system in cells of a common origin that through distinct
      differentiation pathways originate two closely related tissues of the optic
      system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509375
TI  - High-resolution mapping of GenS3 and B11F7 epitopes on myelin-associated
      glycoprotein by expression PCR.
AB  - The GenS3 and B11F7 monoclonal antibodies (MAbs) have been widely used for
      biochemical and immunocytochemical experiments on myelin-associated glycoprotein
      (MAG), a cell adhesion molecule mediating the interaction between myelinating
      glia and axons. We have mapped the epitopes to within several amino acids on Ig
      domain 2 (D2) (amino acids 167-77) and domain 4 (D4) (amino acids 375-388) for
      GenS3 and B11F7, respectively. Domain deletion and substitution mutants of the
      MAG cDNA were first used to map the epitopes to a given domain. In the cases of
      GenS3, insertion mutants were used to resolve the epitope to a small region of
      D2. For the B11F7 epitope, a novel technique combining PCR and in vitro
      transcription and translation was used to generate small C-terminal deletions and
      map the epitope to 13 amino acids. Then, inhibition by peptides corresponding to
      the GenS3 (ELRPELSWLGHE; amino acids 167-177) and B11F7 (QLELPAVTPEDDGE; amino
      acids 375-388) epitopes was used to confirm the position of the epitopes based on
      the mutant data. Interestingly, the GenS3 epitope maps to a region predicted to
      be sequestered within the hydrophobic core of D2. This is consistent with the
      inability of GenS3 to recognize the epitope in native MAG; GenS3 epitope
      recognition occurs only in denatured MAG, where the epitope is more accessible.
      With the definition of the GenS3 and B11F7 epitopes, these antibodies will be
      useful for further structure-function studies on MAG.

PMID- 7509374
TI  - Identification of the palmitoylation site in rat myelin P0 glycoprotein.
AB  - P0 glycoprotein, the major protein of PNS myelin, contains approximately 1 mol of
      covalently bound long-chain fatty acids. To determine the chemical nature of the
      fatty acid-protein linkage, P0 was labeled in rat sciatic nerve slices with
      [3H]palmitic acid and subsequently treated with various reagents. The protein
      bound palmitate was released by incubation with the reducing agents
      dithiothreitol and 2-mercaptoethanol, and with 1 M hydroxylamine at pH 7.5. In
      addition, P0 was deacylated by treatment with 10 mM NaBH4 with the concomitant
      production of [3H]hexadecanol, indicating that the fatty acid is bound in a
      thioester linkage. This conclusion was supported further by the fact that
      deacylation with hydroxylamine generated free thiol groups, which were titrated
      with [14C]-iodoacetamide. To identify the cysteine residue involved in the
      thioester linkage, [14C]carboxyamidomethylated P0 was digested with trypsin and
      the resulting peptides analyzed by reversed-phase HPLC. Identification of the
      radioactive protein fragments by amino acid analysis and amino-terminal peptide
      sequencing revealed that Cys153 in rat P0 glycoprotein is the acylation site. The
      acylated cysteine is located at the junction of the putative transmembrane and
      cytoplasmic domains. This residue is also present in the P0 glycoprotein of other
      species, including human, bovine, mice, and chicken.

PMID- 7509376
TI  - The stability of endogenous tyrosine hydroxylase protein in PC-12 cells differs
      from that expressed in mouse fibroblasts by gene transfer.
AB  - Previous studies have used recombinant retroviruses encoding the tyrosine
      hydroxylase (TH) gene to transduce various cell lines, including fibroblasts (NIH
      3T3), a pituitary tumor cell line (AtT20), and a pancreatic endocrine line (RIN).
      These genetically modified cells, synthesizing either 3,4-dihydroxyphenylalanine,
      dopamine, or both, are potential donors for treatment of Parkinson's disease.
      However, the levels of TH protein in such transduced cells have been low and
      heterogeneous. Using several modified versions of retrovirus vectors encoding TH,
      we demonstrated that protein stability is an important factor governing levels of
      TH in NIH-3T3 fibroblasts. Whereas low levels of TH protein were observed in
      infected NIH-3T3 cells, high levels of a TH-beta gal fusion protein were found.
      This difference was due to a significantly longer half-life of the TH-beta gal
      fusion protein relative to TH alone. However, the TH-beta gal fusion protein was
      found to be enzymatically inactive. We also found that the half-life of the
      endogenous TH protein in PC-12 cells is sevenfold longer than the TH protein in
      transduced fibroblasts, implying that a cell-type specific regulator or mechanism
      may stabilize TH in catecholaminergic cells.

PMID- 7509377
TI  - pp60c-src enhances the acetylcholine receptor-dependent catecholamine release in
      vaccinia virus-infected bovine adrenal chromaffin cells.
AB  - Secretion of catecholamines by adrenal chromaffin cells is a highly regulated
      process that involves serine/threonine and tyrosine phosphorylations. The
      nonreceptor tyrosine kinase pp60c-src is expressed at high levels and localized
      to plasma membranes and secretory vesicle membranes in these cells, suggesting an
      interaction of this enzyme with components of the secretory process. To test the
      hypothesis that pp60c-src is involved in exocytosis, we transiently expressed
      exogenous c-src cDNA using a vaccinia virus vector in primary cultures of bovine
      adrenomedullary chromaffin cells. Chromaffin cells infected with a c-src
      recombinant virus restored the diminished secretory activity accompanying
      infection by wild type virus alone or a control recombinant virus. The level of
      enhanced catecholamine release correlated directly with the time and level of
      exogenous c-src expression. These results could not be attributed to differences
      in cytopathic effects of wild type versus recombinant viruses as assessed by cell
      viability assays, nor to differences in norepinephrine uptake or basal release,
      suggesting that pp60c-src is involved in stimulus-secretion coupling in infected
      cells. Surprisingly, exogenous expression of an enzymatically inactive mutant c
      src also restored catecholamine release, indicating that regions of the
      introduced c-src protein other than the kinase domain may affect catecholamine
      release. Secretory activity was elevated by both forms of c-src in response to
      either nicotine or carbachol (which activate the nicotinic and the
      nicotinic/muscarinic receptors, respectively). In contrast, release of
      catecholamines upon membrane depolarization (as elicited by 55 mM K+) or by
      treatment with the calcium ionophore A23187 was unaffected by either vaccinia
      infection or increased levels of pp60c-src. These results suggest that pp60c-src
      affects secretory processes in vaccinia-infected cells that are activated through
      ligand-gated, but not voltage-gated, ion channels.

PMID- 7509378
TI  - Depolarization and neurotransmitters increase neuronal protein tyrosine
      phosphorylation.
AB  - In rat hippocampal slices and in neurons in primary culture, K(+)-induced
      depolarization increased markedly and rapidly tyrosine phosphorylation of a 110
      kDa protein (pp110) and, to a lesser degree, of a 120-kDa protein (pp120), in a
      calcium-dependent fashion. Glutamate, 1-aminocyclopentane-trans-1,3-dicarboxylic
      acid (an agonist of metabotropic glutamate receptors), and alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (an agonist of ionotropic glutamate receptors)
      stimulated also tyrosine phosphorylation of pp110 and pp120. These effects were
      not observed in astrocytes in primary culture. In hippocampal slices tyrosine
      phosphorylation of pp110 and pp120 was stimulated by Ca(2+)-ionophores and by
      phorbol esters and antagonized by a chelator of intracellular Ca2+ and by drugs
      that inhibit protein kinase C. Stimulation of muscarinic and alpha 1-adrenergic
      receptors increased also tyrosine phosphorylation of pp110 and pp120. These
      results demonstrate that membrane depolarization and stimulation of
      neurotransmitter receptors activate a tyrosine phosphorylation pathway in
      neurons. This pathway involves an increase in intracellular Ca2+ concentrations
      and the activation of protein kinase C. It may provide a biochemical basis for
      some neurotrophic effects of electrical activity and neurotransmitters and may
      contribute to the role of tyrosine phosphorylation in long-term potentiation.

PMID- 7509379
TI  - Paclitaxel: what schedule? What dose?

PMID- 7509380
TI  - Phase I trial of 3-hour infusion of paclitaxel with or without granulocyte colony
      stimulating factor in patients with advanced cancer.
AB  - PURPOSE: We conducted a phase I trial of a 3-hour infusion of Taxol (paclitaxel;
      Bristol-Myers Squibb Co, Princeton, NJ) to identify the maximum-tolerated dose of
      Taxol as a 3-hour infusion with and without granulocyte colony-stimulating factor
      (G-CSF) support. MATERIALS AND METHODS: Thirty-five patients with advanced,
      untreatable malignancies were treated with a 3-hour infusion of Taxol once every
      3 weeks. Groups of three patients were entered at escalating dose levels of Taxol
      in a traditional phase I design in each of two parallel arms: arm A, without G
      CSF, and arm B, with G-CSF. Patients assigned to the G-CSF arm received G-CSF 5
      micrograms/kg/d subcutaneously starting on day 2 for 9 to 14 days. All patients
      were pretreated with dexamethasone, diphenhydramine, and ranitidine, and were
      monitored continuously for cardiac arrhythmias during the first treatment.
      RESULTS: Dose-limiting myelosuppression with Taxol without G-CSF was observed at
      the 250-mg/m2 dose level. The dose-limiting toxicity for Taxol with G-CSF was
      peripheral neuropathy at the 300-mg/m2 dose level. One of 35 patients (2.8%) had
      a grade 3 anaphylactic reaction at 250 mg/m2. No clinically significant cardiac
      arrhythmias were documented. Twenty-seven of 111 courses (24%) were associated
      with grade 3 arthralgias or myalgias requiring narcotics for pain control. Taxol
      plasma concentrations declined in a triexponential fashion, with a final
      elimination half-life of 10 to 12 hours. The peak Taxol plasma concentrations and
      total area under the curve (AUC) increased with increasing doses of Taxol,
      although this increase appeared to be somewhat nonlinear. CONCLUSION: The maximum
      dose of Taxol recommended for phase II and III studies, when administered as a 3
      hour infusion alone and with G-CSF support, is 210 mg/m2 and 250 mg/m2,
      respectively. No increased incidence of hypersensitivity reactions or other side
      effects were observed, with the possible exception of arthralgias and myalgias.
      If ongoing trials demonstrate that a 3-hour infusion is as efficacious as a 24
      hour infusion, we conclude that with proper monitoring and premedication, high
      dose Taxol can be safely administered in the outpatient setting.

PMID- 7509381
TI  - A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses
      of MOPP versus an alteration of MOPP with ABVD: a European Organization for
      Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et
      Marie-Curie controlled clinical trial.
AB  - PURPOSE: We report a prospective randomized study comparing the relative efficacy
      of alternating chemotherapy mechlorethamine, vincristine, procarbazine, and
      prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) with
      the standard MOPP chemotherapy in patients with stage IIIB and IV Hodgkin's
      disease (HD). The purpose is to study the influence of time of remission on
      clinical outcome. PATIENTS AND METHODS: After two courses of MOPP, patients were
      randomized to receive six further courses of MOPP, or two courses of ABVD
      followed by two courses of MOPP and two courses of ABVD. Radiotherapy was given
      to areas presenting with masses > or = 5 cm and to residual masses after course
      no. 4. Evaluation of response (complete remission [CR]) took place after two
      courses (CR2), after four courses (CR4), at the end of chemotherapy (CR8), and
      after additional radiotherapy (CR(CT + RT)). Logistic regression analysis was
      used to study prognostic factors for response at the end of chemotherapy. Cox
      analysis was used to study prognostic factors for survival. Two hundred seven
      patients were registered, 192 (93%) of whom were randomized. RESULTS: The CR rate
      at the end of chemotherapy (CR8) was similar in both arms (57% v 59%). However,
      there were more progressions in the MOPP arm compared with the MOPP/ABVD arm (23%
      v 8%, P = .014). A significantly higher failure-free survival (FFS) rate was
      found in the MOPP/ABVD arm (60% v 43% at 6 years, P = .025). There was no
      difference in the relapse-free survival (RFS) or survival rate. Of patients not
      in CR4, only 28% still reached a CR8. RFS at 6 years of patients with CR4 (69%)
      was not different from that of patients with CR8 (68%); patients with a CR(CT +
      RT)) had a lower RFS rate (48%). CR4 (P < .001) predicted strongly for final
      remission at the end of chemotherapy. Cox analysis showed that age more than 50
      years, six or more involved lymph node areas, no CR by the fourth cycle,
      chemotherapy with MOPP alone, and no radiotherapy were unfavorable factors for
      survival. CONCLUSION: MOPP/ABVD chemotherapy significantly improved response and
      FFS rates, but had no influence on RFS and survival rates. Early CR (CR4) is an
      important factor for final remission and might be used to select a group of
      patients with a good prognosis.

PMID- 7509382
TI  - Efficacy and toxicity of vinblastine, bleomycin, and methotrexate with involved
      field radiotherapy in clinical stage IA and IIA Hodgkin's disease: a British
      National Lymphoma Investigation pilot study.
AB  - PURPOSE: To assess the efficacy and toxicity of vinblastine, bleomycin, and
      methotrexate (VBM) chemotherapy with involved-field radiotherapy in clinical
      stage IA and IIA Hodgkin's disease. PATIENTS AND METHODS: Thirty eligible
      patients with clinical stage IA or IIA Hodgkin's disease, at intermediate risk of
      relapse, were enrolled into a prospective multicenter pilot study. They received
      two cycles of VBM chemotherapy, followed by involved-field radiotherapy and then
      four further cycles of VBM. The median follow-up duration from the start of
      treatment is 30 months. RESULTS: All 26 patients with assessable disease showed
      an objective response after two cycles of VBM (nine complete responses, 17
      partial responses). By the completion of treatment, 27 patients were in complete
      remission; two had stable residual masses, which have not progressed at 26 and 34
      months of follow-up; and one patient who died of treatment-related sepsis was in
      complete remission at that time. Two relapses have occurred, 19 and 28 months
      after starting VBM. Cough and dyspnea developed in 14 of 30 patients, and were
      associated with impairment of pulmonary function tests. Three episodes of
      neutropenic sepsis were recorded. CONCLUSION: VBM with involved-field
      radiotherapy is an effective treatment for early Hodgkin's disease. However, the
      associated toxicity, both pulmonary and hematologic, is severe, making the
      regimen unsuitable for routine use.

PMID- 7509383
TI  - Effect of treatment for Hodgkin's disease on pulmonary function: results of a
      prospective study.
AB  - PURPOSE: Because each of very different treatments for Hodgkin's disease (HD) may
      result in a high rate of cure, attention is currently focused on toxicity. This
      prospective study was designed to assess the effects of mediastinal irradiation
      and bleomycin chemotherapy on pulmonary function. PATIENTS AND METHODS: Patients
      were treated from 1980 to 1990 on randomized controlled trials at Stanford
      University. Pulmonary function was tested before treatment (baseline), early
      after treatment (< 15 months), and more than 36 months posttherapy. Treatment
      options in the 145 patients were grouped as I (mediastinal radiotherapy), II
      (mediastinal radiotherapy plus bleomycin), and III (bleomycin) for analyses of
      variance (ANOVAs). A variety of regression models were used to predict early and
      late effects on pulmonary function. RESULTS: A decrease in forced vital capacity
      (FVC) and diffusing capacity (DLCO) in the first 15 months after treatment
      followed by recovery after 36 months was observed for most patients. Patients who
      received mediastinal radiotherapy (RT) had a more pronounced reduction in
      pulmonary function and less complete recovery. Overall, 3 or more years after
      treatment, 32% of group I patients, 37% of group II patients, and 19% of group
      III patients had FVC values less than 80% of predicted, while only 7% of patients
      had a DLCO less than 80% of predicted. Linear regression identified baseline
      measurement as the only significant predictor of change in percent predicted FVC
      or DLCO; patients with higher baseline values had greater decrements after
      therapy. Mantle RT was the only significant treatment variable, predictive of FVC
      and DLCO within 15 months and FVC at 36 or more months. No patient experienced
      pulmonary toxicity severe enough to require hospitalization. CONCLUSION: This
      prospective analysis of pulmonary function after treatment for HD showed that
      mediastinal RT was the only treatment variable that achieved statistical
      significance. Although there were no significant interactions between mediastinal
      RT and bleomycin or Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)
      chemotherapy, the patient numbers were small after correction for mediastinal
      mass size and drug regimen such that an effect could have been missed. The mild
      reduction in pulmonary function should be factored into the overall assessment of
      morbidity risk for each of the potentially curative treatments included in this
      study. As with all reports of late effects, these data should be interpreted with
      respect to the population tested, details of the treatment administered, methods
      of measurement, and length of follow-up.

PMID- 7509384
TI  - After a treatment breakthrough: a comparison of trial and population-based data
      for advanced testicular cancer.
AB  - PURPOSE: To determine to what extent the benefits of cisplatin-based combination
      chemotherapy have been disseminated to all American men diagnosed with advanced
      testicular cancer. PATIENTS AND METHODS: One hundred seventy-two advanced
      testicular cancer cases from five population-based registries of the
      Surveillance, Epidemiology, and End Results (SEER) Program diagnosed from 1978 to
      1984 were compared with 133 diagnostically comparable cases from the Memorial
      Sloan-Kettering Cancer Center (MSKCC) vinblastine, dactinomycin, and bleomycin
      (VAB) regimens 7 through 9. Exclusions were made in both series for cases with
      elevated markers only, abdominal disease only, or extragonadal tumors. Ratings of
      extent of disease using the Indiana University system (minimal/moderate or
      advanced) were available for the MSKCC cases, and were determined retrospectively
      on the SEER cases based on information abstracted from medical records. RESULTS:
      Among the SEER cases, 89% reported receiving chemotherapy, and 95% of these
      received cisplatin-containing regimens. Survival among the MSKCC patients was
      significantly better than for the SEER cases in the minimal/moderate extent of
      disease category (95% and 73% 3-year survival rate, respectively); however, the
      difference for advanced cases was only marginally significant (52% and 40% 3-year
      survival rates, respectively). Survival did not vary significantly by year of
      diagnosis in either series. CONCLUSION: Although most of the patients in the SEER
      series received cisplatin-based chemotherapy, this alone did not produce results
      equivalent to that in the MSKCC series. Since the patients were selected to be as
      diagnostically comparable as possible at baseline, remaining differences in
      survival may be due to adherence to a fixed regimen and level of dose-intensity,
      adequacy of diagnostic work-up, implementation of salvage therapies and debulking
      surgery, and unknown factors related to who is willing and able to travel to a
      tertiary care center for treatment. Whatever the reason for not achieving optimal
      results in the SEER series, the very modest survival improvements over the time
      period 1978 to 1984 indicates that the differences in outcome between the two
      series were basically stable over the study period.

PMID- 7509386
TI  - Histological evaluation of interleukin-1 beta and collagen in gingival tissue
      from untreated adult periodontitis.
AB  - Interleukin-1 beta (IL-1 beta) may be related to the pathological processes
      associated with periodontitis, primarily due to its ability to induce
      collagenase, increase neutrophil chemotaxis, and stimulate bone resorption. This
      study was designed to histologically quantitate IL-1 beta positive cells from
      various histologic fields in untreated gingivitis/early periodontitis (G/EP)
      versus moderate/severe periodontitis (M/SP) gingival tissues, and associate these
      with collagen loss. Two gingival biopsies from 8 patients were collected, one
      from a G/EP site and one from a M/SP site. Mouse monoclonal antibodies in
      combination with an avidin-biotin-peroxidase system were used to stain for IL-1
      beta, while the van Gieson method was used to stain for collagen in serial
      sections. Collagen loss in G/EP (35%) and M/SP (52%) fields was consistent with
      gingivitis and periodontitis, respectively. IL-1 beta positive cells in combined
      coronal/sulcular (Co/Su) and apical/sulcular (Ap/Su) fields (nearest the
      bacterial insult) were significantly more numerous compared to combined
      coronal/middle (Co/Mi) and apical/middle (Ap/Mi) fields (p < 0.05). While numbers
      and percentages of IL-1 beta positive cells were generally higher in M/SP
      biopsies, differences were not significant. Further, there was no correlation
      between the number of IL-1 beta positive cells and percent collagen loss.
      However, a significant correlation between IL-1 beta positive cells and
      corresponding gingival crevicular fluid IL-1 beta concentrations was noted (r =
      0.65, p = 0.01). Through the use of immunohistochemistry, this study demonstrated
      that the presence of IL-1 beta + cells does not appear to have a direct
      association with collagen loss.

PMID- 7509385
TI  - Adhesion molecule expression in chronic inflammatory periodontal disease tissue.
AB  - Differences in lymphocyte populations have been demonstrated in gingivitis and
      periodontitis lesions. A differential expression of adhesion molecules may play a
      role in lymphocyte trafficking in these tissues. An indirect avidin biotin
      immunoperoxidase technique was used to stain a range of adhesion molecules in
      tissue sections of 21 gingival biopsies from both gingivitis and periodontitis
      subjects. These specimens were placed into three groups according to the size of
      the infiltrate. ICAM-1, PECAM-1 and LECAM-1 expression on mononuclear cells in
      the inflammatory infiltrates increased significantly with increasing size of
      infiltrate. Approximately 50% of these mononuclear cells were LFA-1+ and CD29+.
      When specimens were grouped according to their putative disease status there were
      no significant differences between mononuclear cell adhesion molecule expression
      in small infiltrates from either gingivitis or adult periodontitis subjects. This
      was also the case with larger lesions from both clinical groups. Therefore there
      does not appear to be a differential expression of adhesion molecules on
      lymphocytes in gingivitis and periodontitis tissue. Endothelial cells were
      positive for ICAM-1, PECAM-1, CD29, GMP-140 but negative for ELAM-1. Keratinocyte
      expression of ICAM-1 increased with increasing size of infiltrate although in
      heavy infiltrates, cells in the region of the junctional epithelium which were
      positive in small lesions, became ICAM-1 negative. The upper layers of the oral
      epithelium were positive for LECAM-1 in small infiltrates and with increasing
      size of infiltrate, the lower layers and many of the sulcular and junctional
      epithelium keratinocytes were positive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509387
TI  - Identification, localization and functional analysis of imidazoline and alpha
      adrenergic receptors in canine prostate.
AB  - In nonsurgical management of benign prostatic hyperplasia, drugs which interfere
      with prostate contraction mediated through the alpha-1 adrenergic receptor are
      used. Clonidine acts at alpha adrenergic and I1-imidazoline receptors. In the
      present study, we found the Kd for [3H]clonidine binding to I1 sites in canine
      prostate to be 4 +/- 1 nM; the Bmax was 18 +/- 2 fmol/mg of protein. Inhibition
      of binding by imidazolines and by brain extracts containing putative endogenous
      ligand confirmed the identity of these sites as I1-imidazoline. Autoradiographic
      studies showed localization of both I1 and alpha-2 sites to the glandular
      epithelium. We sought to determine whether in vivo activation of the I1
      imidazoline sites by clonidine mediates its contractile action in canine
      prostate. Dose-response curves were generated for para-aminoclonidine in the
      presence of vehicle alone, yohimbine (alpha-2 antagonist), idazoxan (alpha
      2/I1/I2 antagonist) and prazosin (alpha-1 antagonist). Prazosin was the most
      effective antagonist. Yohimbine was less effective and did not effectively
      discriminate between para-aminoclonidine and phenylephrine, an alpha-1-selective
      agonist. Idazoxan antagonized para-aminoclonidine, but by not more than 50% at
      any dose. These results suggest that clonidine is active primarily at alpha-1
      receptors on prostate smooth muscle in vivo. Thus the function of the I1 and
      alpha-2 receptors in the prostate remains to be determined; however, they may be
      involved in epithelial cell function.

PMID- 7509388
TI  - Efficient coupling of m5 muscarinic acetylcholine receptors to activation of
      nitric oxide synthase.
AB  - The coupling of m5 muscarinic acetylcholine receptors to the generation and
      release of nitric oxide (NO) was investigated. Chinese hamster ovary cells, which
      stably express m5 receptors, were transiently transfected with the gene encoding
      neuronal NO synthase and used as a model system. Increased generation of NO upon
      stimulation of cells by muscarinic agonists was detected by an increase in cyclic
      GMP in admixed mouse neuroblastoma N1E-115 cells or more directly by measuring
      the conversion of L-arginine into L-citrulline. Carbachol increased cyclic GMP
      formation in the mixture of cells in a time- and concentration-dependent manner,
      with a half-maximal response occurring in the nanomolar range. This response was
      significantly attenuated by scavengers of NO or inhibitors of NO synthase. This
      high potency of carbachol was also observed in measurements of L-citrulline
      formation. A series of muscarinic agonists were as efficacious as carbachol in
      stimulating NO synthase, whereas McN-A-343 and pilocarpine were partial agonists
      in this regard. Evidence for an exceptionally high efficiency of coupling of m5
      receptors to this response and its possible implication in the interaction
      between cholinergic and dopaminergic neurotransmission is discussed.

PMID- 7509389
TI  - Pharmacological profile of FK480, a novel cholecystokinin type-A receptor
      antagonist: comparison to loxiglumide.
AB  - The pharmacological profile of FK480[(S)-(+)-N-<1-(2)-fluorophenyl)-3,4,6,7-tetra
      hydro-4-oxo-pyrrolo(3,2,1-jk) (1,4)benzodiaze-pine-3-yl>-1H-indole-2-
      carboxamide], a novel cholecystokinin type-A (CCK-A) receptor antagonist, was
      compared with that of the CCK-A receptor antagonist, loxiglumide. Both FK480 and
      loxiglumide inhibited 125I-labeled CCK-8 (125I-CCK-8) binding to rat pancreatic
      and guinea-pig gallbladder membranes with IC50 values of 0.40 +/- 0.04 and 0.06
      +/- 0.02 nM for FK480 and 330 +/- 66 and 66 +/- 10 nM for loxiglumide,
      respectively. These two agents also inhibited 125I-CCK-8 binding to guinea-pig
      brain (cerebral cortex) receptors with respective IC50 values of 72 +/- 11 nM and
      > 10 microM, indicating less affinity to central receptors. Intravenous
      administration of FK480 (ED50 = 18 micrograms/kg) was 2800 times more potent than
      that of loxiglumide (ED50 = 50 mg/kg) in inhibiting CCK-8-induced pancreatic
      amylase secretion in rats. Furthermore, FK480 had ED50 values of 10 and 8.4
      micrograms/kg, respectively, in antagonizing CCK-8-induced inhibition of charcoal
      meal gastric emptying in mice when administered orally 1 or 5 hr before the CCK
      8. Loxiglumide (ED50 = 23.5 mg/kg, when administered orally 1 hr before the CCK
      8) also antagonized it, but its activity was 2400 times less than that of FK480.
      We conclude that FK480 is a potent, orally effective CCK-A receptor antagonist
      with long duration of action.

PMID- 7509390
TI  - Cyclic AMP regulation of calcium mobilization and amylase release from isolated
      permeabilized rat parotid cells.
AB  - This study examined the mechanistic basis of the synergistic interaction between
      the cyclic AMP (cAMP) and phosphoinositide pathways in salivary amylase
      secretion. cAMP produced a concentration-dependent increase in Ca++ mobilization
      from saponin-permeabilized rat parotid acinar cells. A threshold concentration of
      cAMP (50 microM) significantly increased the peak Ca(++)-releasing activity of
      submaximal concentrations of inositol 1,4,5-trisphosphate (IP3) but did not
      augment the Ca++ mobilization induced by a maximal stimulating concentration of
      IP3 (30 microM). A maximal stimulating concentration of cAMP (500 microM) failed
      to modify the Ca++ releasing action of IP3. IP3-induced Ca++ release was also
      augmented by catalytic subunit of cAMP-dependent protein kinase. A specific
      protein kinase inhibitor reversed this effect. The cAMP-induced Ca++ release was
      blocked by ryanodine but not by heparin, by contrast with the IP3-induced Ca++
      release. Thapsigargin only partially depressed the cAMP response but completely
      abolished the IP3 response. The amylase release elicited by fixed concentrations
      of Ca++ was not further enhanced by either cAMP or forskolin. Thus, unlike
      diacylglycerol, which decreases the Ca++ requirement for secretion by inducing
      activation of protein kinase C, cAMP appears to mediate salivary amylase
      secretion by regulating the sensitivity of parotid cells to the Ca++ mobilizing
      action of IP3. In addition, cAMP possesses a second action, i.e., directly
      eliciting Ca++ mobilization from an IP3-insensitive pool.

PMID- 7509393
TI  - Induction of nitric oxide release by interferon-gamma inhibits vasodilation and
      cyclic GMP increase in bovine isolated mesenteric arteries.
AB  - The influence of interferon (IFN)-gamma on vasodilation was examined in bovine
      isolated mesenteric arteries. Arterial rings were incubated with IFN-gamma (100 U
      ml-1) for 20 hr and subsequently the response to vasodilators was determined
      isometrically in an organ bath. Treatment with IFN-gamma markedly inhibited
      endothelium-dependent relaxation to bradykinin and impaired vasodilation to
      nitroprusside, which was endothelium-independent. The decrease in relaxation was
      correlated with a decrease in bradykinin- and nitroprusside-induced cGMP
      production. Relaxation to the phosphodiesterase inhibitors 3-isobutyl-1
      methylxanthine or zaprinast was not altered after IFN-gamma, which suggests that
      the IFN-gamma effect is specific for guanylate cyclase-activating agonists.
      Nitrite concentration in the incubation medium was increased after IFN-gamma,
      which indicates the induction of nitric oxide release during the incubation
      period. Inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine during
      the 20-hr incubation with IFN-gamma completely prevented the decrease in
      relaxation and cGMP elevation to nitroprusside. We conclude that IFN-gamma
      induces a marked increase in release of arterial-derived nitric oxide resulting
      in a desensitization of guanylate cyclase, which contributes to a decrease in
      relaxation to bradykinin and nitroprusside. These results may implicate the
      existence of an important adaptive process in the regulation of vascular tone
      during pathological situations associated with the induction of nitric oxide
      synthesis.

PMID- 7509391
TI  - Gallium arsenide-induced increase in serum corticosterone is not responsible for
      suppression of the IgM antibody response.
AB  - Previous investigations demonstrated gallium arsenide (GaAs) to be an
      immunosuppressive agent that alters the function of all cell types involved in
      the generation of a primary antibody response. In those studies, GaAs was
      administered as a particulate compound that remained in the lung at least 14 days
      after exposure. The extended presence of the particulate in the lung may induce a
      stress response that leads to the release of endogenous corticosteroids. In
      addition, some of the observed immunomodulatory effects of GaAs were similar to
      immunological alterations reported to be induced by corticosteroids. The present
      studies were designed to determine whether suppression of the immunoglobulin (Ig)
      M antibody-forming calls (AFC) response by GaAs was a result of a GaAs-induced
      increase in serum corticosterone. GaAs (50-200 mg/kg) significantly decreased the
      weights of both the thymus and spleen and the cellularity of the spleen. In
      addition, there was a GaAs-induced decrease in the CD4+/CD8+ thymocyte
      subpopulations and a concomitant increase in CD4+ and CD8+ cells. Within the
      spleen, there were no alterations in the percentages of CD4, CD8 or Ig-positive
      cells. However, when expressed as an absolute cell number, there was a 50%
      decrease in the numbers of CD4+ and CD8+ cells in the spleen. GaAs also dose
      dependently suppressed (50-75%) the IgM AFC response. The GaAs-induced changes in
      cell populations and immune organ weights were correlated with an increase (6- to
      10-fold) in serum corticosterone levels. The treatment of mice with the
      glucocorticoid antagonist mifepristone (also called RU 486) blocked the observed
      alterations in splenic and thymic cell populations induced by GaAs.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7509392
TI  - An antinociceptive effect of capsaicin in the adult mouse mediated by the NH2
      terminus of substance P.
AB  - Capsaicin in the adult animal is believed to evoke a massive release of substance
      P (SP) and a subsequent loss of primary afferent C-fiber activity. Given the
      antinociceptive effect of SP N-terminal metabolites, the present experiments were
      designed to compare behavioral and nociceptive responses after treatments with
      capsaicin or the SP NH2-terminal fragment, SP(1-7), and to determine whether they
      share a common mechanism of action. When adult mice were tested using the hot
      plate assay, 24 hr after intrathecal injections of either capsaicin (0.3-2.6
      nmol) or SP(1-7) (22.5 pmol-10 nmol), a dose-related antinociception was
      observed. The caudally directed biting and scratching behaviors induced by 1 nmol
      of capsaicin injected intrathecally were also greatly reduced 24 hr after either
      2.6 nmol of capsaicin or 10 nmol of SP(1-7). Pretreatment with an antagonist of
      the NH2-terminus of SP, [D-Pro2,D-Phe7]-SP(1-7), prevented the long-term effects
      of capsaicin and of SP(1-7) on capsaicin-induced behaviors in our paradigm at
      doses that the COOH-terminal antagonist of neurokinin activity, [D-Pro2,D-Trp7,9]
      SP, did not. The antinociceptive effect of capsaicin in the adult animal is,
      therefore, mimicked by SP(1-7) and attenuated by [D-Pro2,D-Phe7]-SP(1-7),
      suggesting that the NH2-terminus of SP and its NH2-terminal metabolites, released
      in response to capsaicin, may contribute to the mediation of capsaicin's
      antinociceptive effect.

PMID- 7509395
TI  - Essential reading for ambulatory surgical nurses.

PMID- 7509394
TI  - Novel CCK analogues and bombesin: a detailed analysis between phosphoinositide
      breakdown and high-dose inhibition of pancreatic enzyme secretion in three rodent
      species.
AB  - Cholecystokinin octapeptide (26-33) (CCK-8) stimulates pancreatic amylase
      secretion in a biphasic manner. Amylase secretion is stimulated in a dose
      dependent manner up to a maximal level, but reduced secretion is observed at
      supramaximal concentrations. The downward portion of the dose-response curve has
      been referred to as "high-dose" inhibition. Recent studies with CCK-8 and Boc
      Tyr(SO3H)-Nle-Gyl-Trp-Nle-Asp-2-phenylethylester (JMV-180) using rat acini have
      suggested that activation of the low-affinity CCK receptor leads to enhanced
      phosphoinositide (PI) breakdown, which in turn is responsible for high-dose
      inhibition of enzyme release. However, the secretory effect of JMV-180 varied
      considerably between rat and mouse. To explore further the relationship between
      PI breakdown and high-dose inhibition, we compared the effects of JMV-180 as well
      as the novel cholecystokinin tetrapeptide (30-33) Trp-Met-Asp-Phe-NH2 analogs A
      70874 and A-57282, using rat, mouse and guinea pig pancreatic acini. The maximal
      secretory activity of CCK-8 was lowest (approximately 10% of total cellular
      amylase) in mouse, as compared with guinea pig and rat (approximately 15-20% of
      total amylase). The efficacies of A-70874, A-57282 and JMV-180 for stimulation of
      PI breakdown, relative to CCK-8, were 100, 100 and 45%, respectively, in mouse;
      95, 70 and 20%, respectively, in rat and 75, 40 and 0%, respectively, in guinea
      pig.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509396
TI  - A retrospective review of the Bangour Plastic Surgery Unit, 1941-1991.
AB  - Bangour has been the home of the Lothian Regional Plastic Surgery Service since
      1941. It was originally constructed to be part of the emergency medical service
      hospitals during the Second World War. The lifetime of the Plastic Surgery Unit
      in Bangour finished in February 1992 and with it the end of just over 50 years of
      history. A review of some of the past gives an appropriate historical picture of
      the unit as well as of the changes in plastic surgery.

PMID- 7509398
TI  - How dangerous is TURP?

PMID- 7509397
TI  - Drug-induced gingival overgrowth and its management.
AB  - Gingival overgrowth is associated with the chronic usage of phenytoin,
      cyclosporin and the dihydropyridines. The pathogenesis of this unwanted effect is
      uncertain but appears to be enhanced by plaque-induced gingival inflammation.
      Certain patients appear to be more susceptible to gingival overgrowth and this
      may be related to gingival fibroblast phenotypes. In most cases, treatment
      involves surgical excision, followed by a concentrated oral hygiene programme.
      Recurrence of gingival overgrowth is a persistent problem particularly in the
      'responder' patients. If an alternative, suitable medication is available, it may
      be worth while considering such a change through consultation with the patient's
      physician. Since patients are retaining their teeth into old age, the prevalence
      of this unwanted effect is likely to increase.

PMID- 7509399
TI  - Combination adrenaline and ethanolamine endoscopic injection therapy does not
      impair peptic ulcer healing.
AB  - The acute effects of endoscopic injection therapy given for bleeding peptic ulcer
      and the impact of injection therapy upon peptic ulcer healing were assessed in 70
      patients randomized to conservative treatment or injection with a combination of
      1:100,000 adrenaline and 5% ethanolamine. Injection was not associated with acute
      complications nor did it affect the endoscopic findings 48 hours after injection.
      Ulcer healing on standard doses of H2 receptor drugs was 95% in injected patients
      and 93% in conservatively treated patients at 6 weeks.

PMID- 7509400
TI  - Dental prostheses and the impacted swallowed foreign body.
AB  - A common belief exists that patients who wear false teeth are more likely to
      present with an impacted swallowed foreign body than those with a normal
      dentition. This study reviewed a series of 65 patients (with data available from
      45) who presented with a swallowed impacted foreign body which required
      endoscopic removal under general anaesthesia. With the aid of a questionnaire the
      incidence of dental prostheses in these patients was determined. The number of
      patients in our study who had either false teeth or natural dentition was
      compared with the expected age-related incidence of wearing dental prostheses in
      the general population of the United Kingdom. There were no statistically
      significant differences between these groups. Patients presenting with an
      impacted swallowed foreign body are no more likely to be wearing false teeth than
      any other member of the population.

PMID- 7509402
TI  - Elderly patients with perforated peptic ulcers: factors affecting morbidity and
      mortality.
AB  - Morbidity and mortality of perforated peptic ulcers (PPUs) have been higher when
      they occur in elderly patients. Seventy-three PPUs were reviewed to determine the
      factors accounting for the poor outcome in patients at or above 65 years old
      (elderly PPU). The presentation of 44 young PPUs was compared to 29 elderly PPUs.
      Delay in diagnosis, associated comorbid factors and shock on admission were found
      to be the primary factors. There was a significant difference between the two
      groups in terms of duration of pain before the diagnosis was made (8.2 h vs 16.4
      h) (P < 0.05). The delay in diagnosis was partly due to the vague presentation,
      as 41.4% (11 patients) of the elderly presented with abdominal pain not localized
      in the epigastrium. In addition, 55.2% (16) of elderly patients did not have a
      history of prior ulcer disease and one-third (nine) did not have air under the
      diaphragm on chest X-ray. Significant comorbid factors were present in 65.5%
      compared to 15.9% in the younger group (P < 0.001). Shock on admission was
      present in six (20.7%) elderly patients, but only in one (2.3%) young patient (P
      < 0.05). As a result, morbidity was 89.6% in the elderly group compared to 27.2%
      in the younger patients (P < 0.001). Wound complications accounted for a
      significant proportion of the morbidity. Mortality was 17.2% and 2.3%
      respectively (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509401
TI  - Early results of combined carotid endarterectomy and coronary artery bypass
      grafting in patients with severe coronary and carotid artery disease.
AB  - The management of patients with carotid artery disease who require coronary
      artery bypass grafting (CABG) remains controversial. Several published series
      from the USA (including one with prospective randomization) advocate a combined
      approach of carotid endarterectomy (CEA) followed immediately by coronary artery
      bypass surgery. However, experience of combined carotid endarterectomy and
      coronary bypass grafting has not been previously reported by a centre from the
      United Kingdom. Between 1986 and 1991 we performed this combined procedure on 18
      patients who required myocardial revascularization and had co-existing severe (>
      70%) carotid stenosis. Sixteen patients (89%) had angina and 11 patients (61%)
      had symptomatic carotid artery disease. The perioperative mortality was 5.5% and
      the ipsilateral perioperative stroke rate was 5.5%. These early results are
      encouraging and suggest that further evaluation of combined carotid
      endarterectomy and coronary artery bypass surgery is warranted.

PMID- 7509403
TI  - Pseudoaneurysm of the cystic artery following cholecystectomy.

PMID- 7509404
TI  - Familial adenomatous polyposis: colonic carcinoma in the absence of rectal
      polyposis.

PMID- 7509405
TI  - Three cases of early spontaneous splenic rupture associated with acute viral
      infection.

PMID- 7509406
TI  - Retained gallstones following laparoscopic cholecystectomy.

PMID- 7509407
TI  - Recent advances in high-frequency electrosurgery: development of automated
      systems.
AB  - The principles underlying modern high-frequency electrosurgery are outlined with
      special reference to the development of microprocessor-controlled (intelligent)
      systems and the application of safe electrocoagulation and electrocutting in
      minimal access surgery.

PMID- 7509408
TI  - Syme's amputation: a neglected procedure.
AB  - Over a 9-year period nine patients underwent Syme's amputation, one patient
      undergoing a staged bilateral procedure. Six of the ten amputations were carried
      out for the complications of peripheral vascular disease, including one with
      Buerger's disease who had bilateral amputations. Three patients had amputations
      for infected diabetic gangrene and one amputation was performed as a result of
      trauma. Five patients had previously undergone surgery to improve their
      peripheral circulation. Two patients required a subsequent below knee amputation.
      The indications for and technique of Syme's amputation are discussed.

PMID- 7509409
TI  - Closed intramedullary biopsy for metastatic disease.
AB  - The surgical stabilization of metastatic fractures or impending fractures of long
      bones is recommended with the use of intramedullary nails. While the primary
      tumour has often been diagnosed previously, there are occasions when the fracture
      may be the presenting feature of malignancy. In both circumstances surgical
      oncologists require a histological diagnosis from around the fracture site so
      that any adjuvant therapy can be planned. Open biopsy is often employed although
      a closed method has been used by percutaneous puncture. Although intramedullary
      specimens have been obtained before with long bronchial type biopsy forceps, we
      report a simple and reliable technique for closed biopsy taken from
      intramedullary reamings at the time of fracture fixation. Lesions from both the
      femur and the humerus are amenable to this technique.

PMID- 7509410
TI  - Treatment of pathological fractures of the humerus with Ender nails.
AB  - We have treated 16 consecutive cases of pathological fractures of the humerus
      with multiple Ender's nails introduced distally and without opening the fracture
      site. Stabilization was satisfactory in all cases and provided good pain relief
      and allowed early return of function. The technique is straightforward and has
      advantages over other methods of fixation.

PMID- 7509411
TI  - Colles' fractures: the use of the metacarpal index as a prognostic indicator
      investigated.
AB  - The radiographs of 25 patients who presented to the Whittington Hospital with
      Colles' fractures were studied. Measurements of dorsal angulation and radial
      shortening were made on radiographs taken at presentation, following reduction
      (where performed) and 5 weeks after injury. The presence, and degree, of
      osteoporosis was assessed using the metacarpal index. There was a strong
      correlation between the degree of osteoporosis and age. There was no correlation
      between the degree of osteoporosis, as determined by the metacarpal index, and
      either the severity of the injury or the final result. Thus, the metacarpal index
      is not a useful prognostic indicator as to the radiological outcome of Colles'
      fractures. The single most important factor influencing the radiological result
      was the quality of the initial reduction.

PMID- 7509412
TI  - Free fibular bone grafting for femoral neck fractures: precise graft placement
      using a 'cannulated screw' technique.
AB  - Use of the fibula as a free bone graft has been advocated in the treatment of
      femoral neck fractures, either fresh or where there is established non-union.
      There is debate about the best surgical technique; we present ours, which is
      simple and trouble-free.

PMID- 7509414
TI  - Differential modulation of organophosphate-sensitive muscarinic receptors in rat
      brain by parathion and chlorpyrifos.
AB  - We previously reported similar levels of brain cholinesterase inhibition but
      marked differences in toxicity following acute maximum tolerated doses of the
      organophosphate pesticides parathion and chlorpyrifos. Because extensive
      acetylcholinesterase inhibition often induces compensatory changes in cholinergic
      receptor populations, we compared the effects of parathion and chlorpyrifos on
      brain muscarinic receptors. Adult male rats were treated with vehicle or the
      maximum tolerated dose of parathion (18 mg/kg, sc) or chlorpyrifos (279 mg/kg,
      sc) and observed for signs of acute toxicity. Similarly treated animals were
      sacrificed at 2, 7, or 14 days after treatment for measurement of cholinesterase
      activity and binding to the nonselective muscarinic antagonist [3H]quinuclidinyl
      benzilate, the M2-preferential antagonist [3H]AFDX-384, and the high-affinity
      agonist [3H]cis-methyldioxolane. More acute toxicity was noted after parathion
      treatment. Both insecticides caused similar levels (> 85%) of maximal
      cholinesterase inhibition and reductions (up to 55%) in atropine-sensitive
      quinuclidinyl benzilate binding (i.e., total muscarinic receptors) and [3H]AFDX
      384 binding in cortex and striatum. Parathion also reduced, whereas chlorpyrifos
      increased, total muscarinic receptor binding and [3H]AFDX-384 binding in the
      cerebellum. When tissues were preincubated with paraoxon (10 microM),
      radiolabeling of a subset of quinuclidinyl benzilate binding sites was blocked
      and the apparent densities of these organophosphate-sensitive receptors in all
      three tissues were decreased (16% maximal) by parathion but increased (up to 37%)
      by chlorpyrifos. Similarly, parathion decreased whereas chlorpyrifos increased
      [3H]cis-methyldioxolane binding sites in all three brain regions. We propose that
      differential modulation of these organophosphate-sensitive muscarinic receptors
      contributes to differences in acute toxicity following exposure to these
      pesticides.

PMID- 7509413
TI  - Differential effects of short-term lindane administration on parameters related
      to oxidative stress in rat liver and erythrocytes.
AB  - Parameters related to oxidative stress in rat liver and erythrocytes were studied
      after short-term administration (60 and 90 days) of 1000 ppm of lindane in the
      diet. Lindane induced an oxidative stress condition in the liver, which is
      related to an enhancement in microsomal NADPH-cytochrome c reductase and NADPH
      oxidase activities, superoxide radical formation and cytochrome P450 content,
      produced independently of the time of treatment. Also, decreased activities of
      glutathione peroxidase and catalase were concomitantly observed. Although these
      changes were paralleled by an increase in lipid peroxidation indices, such as
      production of thiobarbituric acid reactants and spontaneous chemiluminescence, no
      evidence of liver injury was obtained. Lindane treatment did not exert
      quantitatively important changes in the pro-oxidant/anti-oxidant status of the
      erythrocyte, with reduction in the red blood cell mass possibly reflecting
      actions of the insecticide on the erythropoietic process.

PMID- 7509415
TI  - Removal of LPS from a Brucella cytoplasmic fraction by affinity chromatography
      with an anti-LPS monoclonal antibody as immunosorbent.
AB  - Affinity chromatography on polymyxin B-Sepharose 4B is one of the most commonly
      used methods for the removal of contaminating lipopolysaccharides (LPS). However,
      the LPS of Brucella spp. do not bind to polymyxin B. An affinity chromatography
      method with an anti-O antigen of Brucella LPS monoclonal antibody as
      immunosorbent was developed. The method produced a 1000-fold reduction in the LPS
      content of the cytoplasmic fraction of B. abortus. The eluted proteins retained
      their antigenicity. The method, which uses mild physiological conditions, is
      simple, effective and reproducible.

PMID- 7509417
TI  - Letter from Cali. Violence in the Americas.

PMID- 7509416
TI  - Human neutrophil cathepsin G is a potent platelet activator.
AB  - PURPOSE: Neutrophil activation has been implicated in the pathophysiologic
      condition of ischemia-reperfusion injury, the formation of arterial aneurysms,
      the progression of myocardial ischemia, and the initiation of deep venous
      thrombosis. Activated neutrophils release cathepsin G, a serine protease, from
      their granules, which may cause platelet activation that leads to intravascular
      thrombosis, tissue infarction, and systemic release of the thrombogenic products
      of platelet granules. This study used flow cytometry to quantify the extent of
      cathepsin G-induced platelet activation and degranulation through changes in the
      expression of platelet surface glycoproteins. METHODS: Increasing concentrations
      of human neutrophil-derived cathepsin G were incubated with washed platelets or
      whole blood from healthy human donors. The platelet surface expression of
      glycoproteins, including P-selectin, a platelet membrane glycoprotein only
      expressed after platelet alpha granule release, were determined by quantifying
      the platelet binding of a panel of fluorescently labeled monoclonal antibodies.
      Results were compared with the effect of a maximal dose of thrombin, the most
      potent known platelet activator. RESULTS: In a washed platelet system, cathepsin
      G increased platelet surface expression of P-selectin (an activation-dependent
      neutrophil binding site), the glycoprotein IIb/IIIa complex (fibrinogen
      receptor), and glycoprotein IV (thrombospondin receptor), and decreased surface
      expression of glycoprotein Ib (von Willebrand factor receptor) to an extent
      comparable to maximal thrombin. However, these effects were not observed in a
      whole blood system. Further experiments revealed that preexposure to plasma
      completely inhibited cathepsin G-induced washed platelet activation and
      degranulation. Prostacyclin treatment of washed platelets markedly inhibited
      cathepsin G-induced platelet activation. CONCLUSIONS: Cathepsin G is a very
      potent platelet agonist and degranulator, comparable to maximal thrombin, which
      alters platelet surface glycoprotein expression for enhanced neutrophil binding
      and effective platelet aggregation. This study helps to elucidate a possible
      pathway through which neutrophils may directly activate platelets, leading to
      intravascular thrombosis, irreversible ischemia, and tissue death in
      cardiovascular disease states. Patients with diseased endothelium that is
      deficient in prostacyclin production may be particularly prone to the detrimental
      effects of neutrophil-derived cathepsin G platelet activation.

PMID- 7509418
TI  - Age-specific reference ranges for prostate-specific antigen.

PMID- 7509420
TI  - [Early diagnosis of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) is considered to develop either on a background of
      preneoplastic lesions as multistep carcinogenesis or on a liver without such a
      lesion as de novo. The latter course can be assumed by our clinical experience of
      imaging diagnosis and by follow up studies of alpha fetoprotein (AFP) producing
      HCCs. Although serial checkup of AFP is important, serological or genetic
      approach is little use for early detection of HCC. At present, imaging diagnosis
      especially ultrasound is the best modality for detecting early developing HCC.
      The most reliable way for the final diagnosis of the detected mass is done by
      aspiration histology using a 21G needle with ultrasound guidance. Recent new
      imaging modalities such as contrast enhanced ultrasound using CO2 microbubbles or
      CTAP are not so reliable as aspiration histology, especially in tumors less than
      15 mm in diameter.

PMID- 7509419
TI  - Neurodevelopment of children exposed in utero to phenytoin and carbamazepine
      monotherapy.
AB  - OBJECTIVE: To compare pregnancy outcome prospectively after phenytoin and
      carbamazepine monotherapy with outcome in matched mother-child pairs exposed to
      nonteratogens to evaluate the relative fetal safety of these drugs. DESIGN: A
      prospective, controlled, and blinded observational study. PATIENTS: Thirty-six
      mother-child pairs exposed to carbamazepine monotherapy and 34 pairs exposed to
      phenytoin monotherapy, all prospectively studied, were compared with mother-child
      pairs exposed to nonteratogens. The controls were matched for maternal age, time
      of consultation, obstetric history, and socioeconomic status. MAIN OUTCOME
      MEASURE: The primary end point of interest was the children's global IQ measured
      by either the Bayley or the McCarthy scale according to their ages. SETTING: A
      teratology consultation program and two neurology services in Toronto, Ontario.
      RESULTS: Children exposed to phenytoin in utero had a mean (+/- SD) global IQ 10
      points lower (95% confidence interval, 4.9 to 15.8 points) than their matched
      controls (113.4 +/- 13.1 and 103.1 +/- 25.1; P = .038). The Reynell language
      development scores followed a similar trend, with children exposed to phenytoin
      scoring significantly lower than their controls. Phenytoin-exposed children had a
      global IQ of 84 or less significantly more often than the control group (P <
      .01). Children exposed in utero to carbamazepine did not differ from their
      controls on any of the neurobehavioral tests. CONCLUSIONS: Our study suggests a
      clinically important negative effect of phenytoin on neurobehavioral development,
      independent of maternal or environmental factors, causing a substantial number of
      children to achieve a lower score than expected on cognitive tests. No similar
      effects could be shown after gestational use of carbamazepine.

PMID- 7509421
TI  - [The heterogeneity of periodic acid-thionin schiff/KOH/PAS staining property and
      the histological grading of atypia in colorectal carcinoma and adenoma].
AB  - To assess the mucin changes associated with the development of colorectal cancer,
      the periodic acid-thionin schiff (PAT)/KOH/PAS staining properties of 38 advanced
      carcinomas, 8 submucosal invasive carcinoma, 29 mucosal carcinomas (adenomas with
      severe atypia), 19 adenomas with moderate atypia and 38 adenomas with mild atypia
      were studied with special attention to the heterogeneity of staining property
      within each lesion. 6 submucosal carcinomas and 28 mucosal carcinomas were judged
      to have benign adenomatous portion using hematoxilin-eosin staining. The more
      advanced the carcinomas, or the higher the grade of atypia of adenomas, the fewer
      the lesions of which goblet cell mucus (GCM) and the mucus at the luminal surface
      or that in the luminal accumulation (SC) stained red. SC frequently stained bluer
      than GCM in highly atypical glands. The staining properties of benign adenomatous
      portions concomitant with submucosal or mucosal carcinomas were similar to those
      of benign adenomas, but not to their carcinomatous foci. These findings suggest
      that the changes in the PAT/KOH/PAS staining property associated with the
      development of colorectal carcinoma mainly occur in SC, and that the majority of
      submucosal and mucosal carcinomas were 'carcinoma in adenoma'.

PMID- 7509422
TI  - Phenylephrine-induced rhythmic activity in the rabbit ear artery.
AB  - Isolated rabbit ear arteries displayed rhythmic contractions when stimulated with
      alpha 1 agonist phenylephrine. These rhythmic responses were greatly attenuated
      by endothelium removal. However, contractions were sufficiently rhythmic in the
      arteries treated with NG-monomethyl-L-arginine, NG-nitro-L-arginine and
      indomethacin, synthetic inhibitors of endothelium-derived nitric oxide and
      prostanoids. Phenylephrine-induced rhythmic contractions were converted to tonic
      contractions by the blockade both of the voltage-dependent Ca2+ channel and the
      Ca(2+)-activated K+ channel by nifedipine and charybdotoxin, respectively. In
      contrast, glibenclamide, an ATP-sensitive K+ channel antagonist, did not alter
      the rhythmic contractions. These results suggest that endothelium may in part
      regulate the phenylephrine-induced rhythmic contractions in the rabbit ear
      artery, although endothelium-derived nitric oxide or prostanoids may not be
      involved in these responses. These endothelium-involved rhythmic responses may be
      attributed to the activation of the voltage-dependent Ca2+ channel and the Ca(2+)
      activated K+ channel.

PMID- 7509423
TI  - [Pleuropulmonary aspergillosis with defective neutrophil functions--G-CSF effects
      on neutrophil functions].
AB  - A 66-year-old man was admitted to our hospital with productive cough and fever.
      Chest X-ray films showed pleural thickening of the right apex and calcification
      of the lung field. Antibiotic therapy was administered but no improvement was
      obtained. Chest CT scan revealed pleural thickening with effusion in the right
      apex. Needle aspiration biopsy was performed and Aspergillus fumigatus was
      isolated from pleural fluid. We began pleural drainage and intrapleural infusion
      of miconazole, with systemic administration of miconazole, amphotericin B and
      fluconazole. In spite of normal bone marrow findings, the neutrophil functions,
      NAP score and phagocytosis, of the patient were found to be subnormal. We
      commenced to treatment with granulocyte colony stimulating factor and his
      neutrophil functions improved (NAP score: 156-->309.5, phagocytosis: 64.9-
      >70.0%). However, his fever persisted and he died following cardiopulmonary
      arrest. Autopsy revealed Aspergillus mycelia invading the visceral pleura. No
      intrapulmonary lesions caused by Aspergillus were found.

PMID- 7509425
TI  - [Results of laser coagulation of central retinal vein occlusion].
AB  - BACKGROUND: In the literature laser treatment in ischemic central retinal vein
      occlusion (CRVO) is established to prevent iris neovascularization. We
      investigated the relationship of morphological and fluorescein angiographic
      findings with the results of laser treatment. PATIENTS AND METHODS: In 70 (56%)
      of 125 examined patients with central retinal vein occlusion laser treatment was
      performed. Indications were either ischemic type of occlusion or macular edema
      with visual acuity < or = 0.5. RESULTS: The results compare visual acuity before
      and after laser treatment (three months and 11.5 months on average) examined by
      Wilcoxon-test. There was no significant improvement in visual acuity (p = 0.62).
      After laser treatment 3 (9%) patients with ischemic CRVO developed iris
      neovascularization and 2 (6%) neovascular glaucoma. There was no correlation
      between visual outcome and ischemia type (non ischemic type p = 0.61, ischemic
      type p = 0.67), maculopathy (cystoid macula edema p = 0.87, ischemic maculopathy
      p = 0.5) and internal diseases (hypertension p = 0.43, diabetes mellitus p =
      0.74). CONCLUSIONS: The results of this study indicate that there is no
      significant visual improvement in patients with CRVO after laser treatment. There
      are no morphological and angiographic findings indicating a subgroup with good
      visual prognosis.

PMID- 7509426
TI  - [Isovolemic hemodilution in central retinal vein occlusion in patients less than
      50 years of age].
AB  - AIM--Aim of the study was investigation of the effect of isovolemic hemodilution
      in patients younger than 50 years on the course of central retinal vein occlusion
      (CRVO) and to compare these results with those of older patients with CRVO.
      PATIENTS AND METHODS--We performed a prospective study on 35 patients younger
      than 50 years who were suffering from a central retinal vein occlusion. These
      patients were all treated by isovolemic hemodilution and compared to a group of
      older patients with CRVO with the same treatment. RESULTS--About 66% of the
      younger patients were men compared to only 46% in older patients. At least two
      cardiovascular risk factors were present in 8.5% of the younger and 54% of the
      older patients. 16 eyes showed the ischemic, 19 the nonischemic type of CRVO, a
      similar distribution as in older patients. The course of the disease was more
      favourable in younger patients, although ocular complications may occur in
      ischemic CRVO. Isovolemic hemodilution did not change the initial visual acuity
      of eyes with nonischemic CRVO, but led to an improvement in 56% of the eyes with
      ischemic CRVO. This means only a minor difference to the course of CRVO in
      hemodiluted older patients. CONCLUSION--In general, there is no principal
      difference between the CRVO in younger and older patients, but the course is more
      favourable in younger patients. On the basis of these findings we recommend
      isovolemic hemodilution in younger patients with ischemic CRVO.

PMID- 7509424
TI  - [A case of large cell carcinoma of the lung producing granulocyte colony
      stimulating factor].
AB  - A 48-year-old female was admitted complaining of cough and right chest pain. A
      chest X-ray showed a tumorous mass in the right lower lung field and hilar and
      mediastinal lymphadenopathy. The patient underwent transbronchial lung biopsy,
      and was diagnosed as having a malignant tumor. Because a metastatic lesion was
      detected in the left lung filed, we opted for chemotherapy. The white blood cell
      count rose to 103,700/mm3 and 190,000/mm3 in the fifth and sixth month after
      hospitalization, respectively. The serum granulocyte colony-stimulating factor (G
      CSF) level by enzyme immunoassay exceeded 1000 pg/ml. The histological diagnosis
      of large cell carcinoma was made from the specimen obtained by percutaneous
      needle biopsy of the lung. The carcinoma cells in this specimen, showed positive
      staining with anti-G-CSF monoclonal antibody.

PMID- 7509427
TI  - Anisotropy in fitness landscapes.
AB  - A definition of empirical anisotropy is proposed, which allows for a quantitative
      measurement. This theory is applied to RNA free energy landscapes. It is shown
      that the biophysical GCAU landscapes are highly anisotropic, while the synthetic
      GCXK landscapes become isotropic for long chains. The major part of the
      anisotropy of the GCAU landscapes arises from the difference of the G identical
      to C and the A = U stacking parameters.

PMID- 7509428
TI  - Phospholipid analysis of alveolar macrophages and bronchoalveolar lavage fluid
      following bleomycin administration to rabbits.
AB  - Changes in the lipid metabolism of the lung during pulmonary injury were
      investigated by quantitative and qualitative analysis of phospholipids in
      pulmonary surfactant and alveolar macrophages (AM) obtained from rabbits that had
      been given a single transtracheal injection of bleomycin hydrochloride (BLM) 0,
      7, 14, 21, and 28 days previously. BLM treatment increased the phospholipid
      content of both bronchoalveolar lavage (BAL) supernatant fluids and BAL cells.
      Furthermore, the proportion of phosphatidylcholine (PC) showed an increase in BAL
      cells during the development of pulmonary injury, and BLM treatment appeared to
      cause transformation of AM to foamy AM. Lipid analyses of the foamy AM revealed
      that their phospholipid content was increased, and that the percentage of PC with
      palmitic acid was elevated. Thus it appears that accumulation of phospholipids
      derived from pulmonary surfactant contributes to the increase in phospholipids
      and PC in BAL cells. These findings indicate that BLM treatment produces an
      alteration in the amount and composition of AM phospholipids, and also in BAL
      supernatant fluids.

PMID- 7509430
TI  - Surgical therapy for squamous-cell carcinoma of the oesophagus.

PMID- 7509429
TI  - Immunohistochemical monitoring of the effect of a synthetic fibronectin-like
      peptide (Arg-Gly-Asp) on the age-related changes in the isolated human
      corneoscleral tissue of glaucomatous eyes.
AB  - Fibronectin, an adhesion glycoprotein has been detected and localized in samples
      of the trabecular meshwork from eight normotensive and 30 glaucomatous human eyes
      of various ages by means of the indirect immunoperoxidase staining technique.
      Fibronectin concentration in the trabecular meshwork tissue was evaluated by
      morphometric analysis. Deposits of the adhesion glycoprotein fibronectin were
      shown to be spread in the ocular drainage outflow system from patients along with
      progressive primary open-angle glaucoma (POAG). The fibronectin level
      quantitatively evaluated in serial cross-sections of trabecular meshwork,
      appeared to be increased during ageing and more rapidly in the event of POAG
      development. The active amino acid sequence in fibronectin is an arginine-glycine
      aspartic acid tripeptide (Arg-Gly-Asp) and it was shown that the synthetic Arg
      Gly-Asp peptide specifically inhibited the adhesive function of fibronectin in
      trabecular meshwork samples when incubated for 30 min at a concentration of 1-2
      mg/ml. The peptide concentration necessary for a 50% decrease of the maximal
      fibronectin level in the trabecular meshwork specimen derived from patients with
      moderately advanced POAG stage, was about 1 mg/ml. Immunohistochemical staining
      exhibited a fainter fibronectin staining in trabecular tissues including the
      external trabecular layers and subendothelial region of Schlemm's canal, in
      samples incubated with the synthetic peptide compared with the same tissue
      explants before peptide treatment. It may be concluded that the adhesion control
      system is likely to play an important role in development and maintenance of
      tissue architecture and specialization of the normal human trabecular meshwork.

PMID- 7509431
TI  - RANTES role in rheumatoid arthritis.

PMID- 7509432
TI  - False detection of negative-strand hepatitis C virus RNA.

PMID- 7509433
TI  - Pre-eclampsia and serum antibodies to oxidised low-density lipoprotein.
AB  - Oxidised low-density lipoprotein (Ox-LDL) has been associated with arterial foam
      cell formation, and autoantibodies to Ox-LDL are present in human serum. Lipid
      peroxidation is enhanced in pre-eclampsia. We assessed whether the titre of IgG
      autoantibody to an epitope of Ox-LDL, malondialdehyde-conjugated low-density
      lipoprotein (MDA-LDL), was increased in the sera of pre-eclamptic patients. 16
      such patients had significantly higher mean titres of autoantibodies to MDA-LDL
      than healthy pregnant women (p = 0.028). In a multiple regression model, pre
      eclamptic patients still had a significantly higher mean titre (p = 0.048).
      Enhanced lipid peroxidation may be involved in the foam-cell formation of decidua
      and in the pathogenesis of pre-eclampsia.

PMID- 7509434
TI  - Involvement of granule, basket and stellate neurons but not Purkinje or Golgi
      cells in cerebellar cGMP increases in vivo.
AB  - Recent immunocytochemical studies of cerebellar nitric oxide synthase (NOS) and
      cGMP have aided dramatically in defining possible cellular sources of cGMP
      generation in the signal transduction cascade evoked by excitatory amino acids in
      the cerebellum. Using a mouse mutant deficient in cerebellar Purkinje cells
      ("nervous" mouse) and chemical lesions of cerebellar neurons with
      methylazoxymethanol (MAM), we have examined in vivo generation of cGMP to
      determine the roles of different cerebellar neuronal populations. In the case of
      "nervous" mice, our data indicate that cerebellar Purkinje cells are not required
      for NMDA-dependent increases in cGMP in the cerebellum. In marked contrast, MAM
      lesions which reduce granule but not Golgi cells in the granule cell layer and
      reduce basket and stellate cells in the molecular layer, dramatically reduced the
      ability of NMDA to increase cerebellar cGMP. These data support
      immunocytochemical data of cerebellar NOS pools and indicate the importance of
      granule, basket and possibly stellate cells in the generation of nitric oxide,
      which in turn activates guanylate cyclase, in a diversity of cells, to increase
      cerebellar cGMP levels.

PMID- 7509435
TI  - Histamine H1 receptor activation mediates the preferential release of adrenaline
      in the rat adrenal gland.
AB  - Histamine elicited the release of catecholamines from "in vitro" perfused rat
      adrenals with an EC50 of 3 microM. This concentration was in the same range as
      those which caused a fall in the arterial blood pressure when infused
      intravenously in anaesthetized rats. Histamine stimulation was potently blocked
      by dexclorfeniramine (IC50 = 300 pM), but unaffected by ranitidine, suggesting
      the involvement of H1 receptors. Histamine release preferentially adrenaline.
      Mast cells were not detected within adrenal medulla by histochemical techniques.
      Compound 48/80 did not trigger catecholamine release. Catecholamine secretion
      evoked by splanchnic nerves stimulation was not modified by a combination of H1
      and H2 antagonists. In conclusion, the histamine that elicited adrenaline release
      from rat adrenals comes from blood circulation not from local mast cells or
      splanchnic nerves. These effects are mediated through the activation of H1
      receptors.

PMID- 7509436
TI  - A truncated isoform of the thyrotropin-releasing hormone receptor is expressed in
      the rat central nervous system as well as in the pituitary gland.
AB  - Using the reverse transcription-polymerase chain reaction (RT-PCR), a cDNA
      encoding the entire rat thyrotropin-releasing hormone receptor (TRH-R) was
      isolated from normal rat pituitary gland mRNA. In addition, a novel truncated
      isoform of TRH-R which lacks 52 base pairs (bp) in the carboxyl (C-) terminal
      tail was isolated. This truncation, probably generated by alternate splicing,
      causes a frame-shift and results in a truncated TRH-R 25 amino acids shorter and
      with a different C-terminal amino acid sequence than the longer type receptor.
      This truncated TRH-R mRNA, along with the longer receptor form, was found to be
      expressed throughout the rat pituitary gland and brain.

PMID- 7509438
TI  - Homomers of alpha 8 and alpha 7 subunits of nicotinic receptors exhibit similar
      channel but contrasting binding site properties.
AB  - alpha 8 subunits of alpha-bungarotoxin-sensitive chick neuronal nicotinic
      acetylcholine receptors expressed in Xenopus oocytes from cRNA are shown to form
      homomeric, acetylcholine-gated, rapidly desensitizing, inwardly rectifying,
      Ca(2+)-permeable cation channels similar to those of alpha 7 homomers. alpha 8
      forms oligomers of several sizes, of which < 14% are expressed on the oocyte
      surface, which is less efficient than for alpha 7 homomers. alpha 8 homomers are
      more sensitive to agonists but less sensitive to antagonists than are alpha 7
      homomers, and some agonists for alpha 8 homomers are partial agonists or
      antagonists for alpha 7 homomers. The pharmacological properties of homomers of
      alpha 8 and alpha 7 subunits generally reflect those of native alpha 8 and alpha
      7 receptors.

PMID- 7509437
TI  - Cloning and expression of the alpha 2C-adrenergic receptor from the OK cell line.
AB  - The alpha 2-adrenergic receptors have been divided into four pharmacological
      subtypes, alpha 2A, alpha 2B, alpha 2C, and alpha 2D. The OK cell line, a cell
      line derived from an opossum kidney, expresses the alpha 2C-adrenergic receptor
      and is the prototypical cell line for the alpha 2C receptor subtype. The cloned
      human alpha 2C-C4 and rat RG10 receptors have been shown to express alpha 2C
      pharmacology. Here we report the cloning and expression of the OK alpha 2C
      adrenergic receptor, OKc2. The receptor has 64% deduced amino acid identity and
      21% similarity to the alpha 2-C4 receptor, giving an overall similarity of 85%.
      The clone, expressed in Chinese hamster ovary cells, has a pharmacology that
      correlates very well (r = 0.97) with that of the native OK cell alpha 2C
      adrenergic receptor, and it is negatively coupled to adenylyl cyclase.

PMID- 7509439
TI  - Characterization of the binding of [3H]substance P to the nicotinic acetylcholine
      receptor of Torpedo electroplaque.
AB  - The binding of [3H]substance P to nicotinic acetylcholine receptor-enriched
      Torpedo electroplaque membranes was characterized. In the absence of cholinergic
      agonist, [3H]substance P binding was displaced by unlabeled substance P with an
      IC50 of 31 +/- 7 microM. In the presence of 10 mM carbamylcholine, displacement
      reflected two populations of binding sites with IC50 values of 0.93 +/- 0.39 and
      30 +/- 5 microM, with the higher affinity component contributing 69 +/- 2% of the
      inhibition. Equilibrium binding parameters were calculated by transformation of
      the concentration dependences of inhibition into saturation isotherms. In the
      absence of agonist, substance P bound with a Kd of 42 +/- 7 microM to 3-4
      sites/alpha-bungarotoxin binding site. In the presence of agonist, substance P
      bound to two sites, a low affinity site not significantly different from that
      seen in the absence of agonist (Kd = 25 +/- 8 microM, approximately 3 sites/alpha
      bungarotoxin site) and a high affinity site with a Kd of 0.55 +/- 0.32 microM
      (approximately 1 site/2 alpha-bungarotoxin sites, 1 site/receptor). The increase
      in substance P binding induced by carbamylcholine was blocked by the nicotinic
      antagonists alpha-bungarotoxin and d-tubocurarine but was not affected by the
      muscarinic antagonist atropine. The concentration dependence of the
      carbamylcholine-induced increase had two components, with EC50 values for the
      agonist of 9.1 +/- 4.2 microM (56 +/- 16% of the increase) and 1.3 +/- 0.5 mM.
      The structural specificity of agonist-dependent high affinity substance P binding
      was identical to that seen for inhibition of nicotinic receptor activation and
      substantially different from that of binding to the G protein-coupled tachykinin
      receptors. From the time courses of association, it appears that substance P
      binds preferentially to a transient agonist-induced receptor state. The gamma and
      delta subunits of the receptor were specifically labeled in an agonist-dependent
      manner after cross-linking of [3H]substance P to the receptor with the
      bifunctional cross-linking reagent bis[2-(succinimidooxycarbonyloxy)ethyl]sulfone
      or after photoaffinity labeling of the receptor with 125I-p-benzoylphenylalanine
      substance P. These results demonstrate the existence of a high affinity agonist
      induced binding site for substance P on the nicotinic acetylcholine receptor that
      probably mediates the noncompetitive inhibition by the peptide of receptor
      activation.

PMID- 7509440
TI  - Septide: an agonist for the NK1 receptor acting at a site distinct from substance
      P.
AB  - The hexapeptide [pGlu6,Pro9]substance P (SP)6-11, septide, has been shown to be
      an agonist as potent as SP in eliciting smooth muscle contraction in several in
      vitro preparations, while being a poor competitor of labeled SP binding. These
      results, as well as other pharmacological data, have suggested the existence of
      either a specific septide receptor or a septide site on the neurokinin (NK)1
      receptor distinct from that for SP. We have used rat recombinant NK1 receptor
      expressed in COS-1 cells to address this issue. Both functional (agonist-induced
      inositol phosphate accumulation) and radioligand binding studies were conducted
      on transiently transfected cells. SP and septide elicited similar maximal
      increases (4-6-fold) in inositol phosphate levels in transfected cells, with EC50
      values of 0.05 +/- 0.02 nM for SP and 5 +/- 2 nM for septide. No additivity of
      the maximal responses to the two agonists was observed, and neither agonist
      evoked any response in sham-transfected cells. RP 67580 was a competitive
      inhibitor of SP responses, with an inhibition constant (KB) of 13 +/- 2 nM, in
      agreement with displacement studies of [3H]SP binding to membranes and intact
      transfected cells (Ki values of 10 +/- 4 nM, and 1.16 +/- 0.06 nM, respectively).
      In comparison, septide responses were inhibited by RP 67580 in an uncompetitive
      fashion, with an apparent KB* value of 1.5 +/- 0.2 nM. Septide was a weak
      competitor of [3H]SP binding, with dissociation constants (Ki) of 2.9 +/- 0.6
      microM and 3.7 +/- 0.9 microM for membranes and intact transfected cells,
      respectively. Similarly, septide at concentrations up to 10 microM did not affect
      [3H]RP 67580 binding. In conclusion, we have demonstrated that septide is a
      potent functional agonist of the NK1 receptor but it seems to act at a specific
      subsite different from that for SP. Although not ruling out the existence of
      selective septide receptors in some tissues, these results could explain some of
      the discrepancies with regard to the pharmacological properties of septide.
      Furthermore, a specific septide site on the NK1 receptor could represent an
      original pharmacological target.

PMID- 7509443
TI  - The agonist binding site of the gamma-aminobutyric acid type A channel is not
      formed by the extracellular cysteine loop.
AB  - The amino-terminal extracellular domain of the subunits comprising the gamma
      aminobutyric acid (GABA) receptor contains two cysteine residues (designated at
      relative positions 1 and 15) separated by 13 amino acids. These two cysteines
      (presumably disulfide bonded) are located approximately 150 amino acids from the
      amino terminus. There is significant homology in the amino acid sequence of this
      cysteine loop both between the different subunits of the GABA receptor and with
      subunits of other members of this ligand-gated ion channel superfamily (nicotinic
      acetylcholine- and glycine-activated ion channels). A number of highly conserved
      amino acids within the cysteine loop have been postulated to play a role in
      agonist binding. Here, using site-directed mutagenesis and oocyte expression, we
      have examined the effects of mutating amino acids comprising the cysteine loop on
      the activation of recombinant GABA channels composed of rat alpha 1, beta 2 and
      gamma 2 subunits. Preventing the formation of the putative cysteine-cysteine
      disulfide bond in any of the subunits, by mutating the cysteine at position 15 to
      serine, prevented the functional expression of that subunit. For example,
      coexpression of gamma C15S with wild-type alpha and beta subunits resulted in
      GABA-activated currents with properties identical to those of GABA-activated
      currents from coexpression of alpha and beta subunits alone. These properties
      included sensitivity to activation by GABA (similar EC50 values), blockade by
      Zn2+, and lack of modulation by the benzodiazepine diazepam. We also mutated
      conserved amino acids in the beta subunit that had been specifically proposed to
      form the GABA binding site (beta R6, beta Y8, and beta D11). These mutations (as
      well as several others within or adjacent to the cysteine loop) produced either a
      very moderate effect or no effect on GABA sensitivity, suggesting that these
      particular amino acids do not play a key role in activation of the GABA channel.
      The data presented in this study support a role for the cysteine loop in subunit
      assembly, rather than channel activation.

PMID- 7509442
TI  - Maitotoxin activates a nonselective cation channel and stimulates Ca2+ entry in
      MDCK renal epithelial cells.
AB  - We examined the mechanisms of maitotoxin (MTX), a water-soluble polyether from
      the marine dinoflagellate Gambierdiscus toxicus, in stimulation of Ca2+ entry
      into Mardin-Darby canine kidney cells. In the presence of bath Ca2+, MTX (3 nM)
      caused an elevation of the intracellular calcium concentration ([Ca2+]i), which
      was partially inhibited by SK&F 96365 (25 microM) or La3+ (100 microM). A
      stimulation of Ca(2+)-dependent K+ channels in cell-attached membrane patches
      coincided with this rise in [Ca2+]i and was also partially inhibited by SK&F
      96365. Before the rise in [Ca2+]i, a nonselective cation current (Ins), studied
      by the whole-cell patch-clamp technique, was irreversibly activated. Ins poorly
      discriminated between Na+, K+, and Cs+, was unaffected by replacement of Cl- with
      gluconate-, and was not voltage gated. MTX-induced Ins was partially blocked by
      La3+ ions (100 microM) but not by SK&F 96365 (25 microM) or nifedipine (10
      microM). SK&F 96365 by itself induced a small but significant stimulation of Ins
      and a rise in [Ca2+]i. The activation of Ins by MTX was instantaneous and
      depended on the presence of extracellular Ca2+ ions. In the absence of other
      cations, the inward current of Ins was dependent on the bath Ca2+ concentration.
      Cell-attached and excised single-channel measurements revealed that MTX activated
      a SK&F 96365-insensitive, approximately 40-pS, nonselective cation channel from
      the outside. We conclude that the initial action of MTX is the stimulation of a
      nonselective cation channel, which requires the presence of extracellular Ca2+
      ions. The subsequent rise in [Ca2+]i is at least in part caused by another, SK&F
      96365-sensitive, Ca2+ entry pathway, which may be activated as a result of or
      independently of Ins.

PMID- 7509441
TI  - The species selectivity of chemically distinct tachykinin nonpeptide antagonists
      is dependent on common divergent residues of the rat and human neurokinin-1
      receptors.
AB  - During evolution mutations have occurred in peptide receptors that are neutral
      with respect to binding of the natural peptide ligand but frequently affect the
      binding of nonpeptide antagonists. By systematically introducing the nonconserved
      residues from the human neurokinin (NK)-1 receptor into the corresponding rat
      receptor we have attempted to localize the structural elements that are
      responsible for 15-76-fold higher affinity of three tachykinin nonpeptide
      antagonists for the human receptor, compared with the corresponding rat receptor.
      Surprisingly, exchange of the four divergent residues located around the
      previously located apparent binding site for CP 96,345 and FK 888 at the top of
      transmembrane segment (TM) V and VI, either alone or as a group, did not affect
      the binding of these nonpeptide compounds. However, substitution of Ser290 in TM
      VII of the rat receptor with isoleucine present in the human receptor increased
      the affinity for FK 888 20-fold and that for CP 96345 6-fold, corresponding to an
      affinity that was only about 4-fold less than the affinity for the human NK-1
      receptor. Full human-like affinity for FK 888 and CP 96,345 could be conveyed to
      the rat receptor by the combined substitution of Ser290 in TM VII to isoleucine
      and Leu116 in TM III to valine. The NK-2 receptor-selective compound SR 48,968
      was found to bind with low affinity to the human NK-1 receptor but with 15-fold
      even lower affinity to the rat receptor. Substitution of residue 290, which is
      situated within the previously located binding site for this compound, could
      completely account for this difference. These data demonstrate that the species
      selectivities of the nonpeptide antagonists CP 96345, FK 888, and SR 48,968,
      independently of clear differences in their chemical structures and modes of
      discovery, have a similar structural basis, being dependent on two divergent
      residues that apparently are not involved in peptide agonist binding.

PMID- 7509444
TI  - Gene structure and alternative splicing of XFG 5-1, a X. laevis Zn finger protein
      with RNA homopolymer binding activity.
AB  - We describe the fine-structure of the Xenopus laevis XFG 5-1 gene which codes for
      an RNA homopolymer binding Zn finger protein of the FAR (Finger Associated
      Repeat) subfamily. The gene contains six exons, i.e., a leader exon (I), four
      exons (II-V), each of them encoding one individual copy of the FAR repeat, and
      one exon (VI) encoding the linker as well as the complete multifinger-region of
      the corresponding protein. Isolation and characterization of distinct cDNAs
      revealed that primary transcripts are alternatively spliced, thereby leading
      either to mRNAs containing different copy numbers of the FAR repeat or, by
      utilization of an alternative splice acceptor site in front of exon VI, to an
      extension of the linker region between the FAR repeats and the multifinger
      domain. We also describe the fine-structure of a closely related gene, termed XFG
      5-2, which is located downstream to the XFG 5-1 gene. The general structural
      organization in both genes is identical, but point mutations should give rise to
      a XFG 5-2 protein with a different number of Zn finger units.

PMID- 7509445
TI  - The signalling pathways of interleukin-6 and gamma interferon converge by the
      activation of different transcription factors which bind to common responsive DNA
      elements.
AB  - Interleukin-6 (IL-6) and gamma interferon (IFN-gamma) induce a partially
      overlapping set of genes, including the genes for interferon regulatory factor 1
      (IRF-1), intercellular adhesion molecule 1 (ICAM-1), and the acute-phase protein
      alpha 2-macroglobulin. We report here that the rat alpha 2-macroglobulin promoter
      is activated by IFN-gamma in human hepatoma (HepG2) cells and that the IFN-gamma
      response element maps to the same site previously defined as the acute-phase
      response element (APRE), which binds the IL-6-activated transcription factor APRF
      (acute-phase response factor). As was reported for fibroblasts, the IFN-gamma
      regulated transcription factor GAF is phosphorylated at tyrosine after IFN-gamma
      treatment of HepG2 cells. IFN-gamma posttranslationally activates a protein which
      specifically binds to the alpha 2-macroglobulin APRE. This protein is shown to be
      identical or closely related to GAF. Although APRF and GAF are shown to represent
      different proteins, their binding sequence specificities are very similar. APRF
      and GAF bind equally well to the APRE sequences of various acute-phase protein
      genes as well as to the IFN-gamma response elements of the IRF-1, ICAM-1, and
      other IFN-gamma-inducible genes. Transient transfection analysis revealed that
      the IFN-gamma response elements of the IRF-1 and ICAM-1 promoters are able to
      confer responsiveness to both IFN-gamma and IL-6 onto a heterologous promoter.
      Therefore, APRF and GAF are likely to be involved in the transcriptional
      induction of these immediate-early genes by IL-6 and IFN-gamma, respectively.
      Taken together, these results demonstrate that two functionally distinct
      hormones, IL-6 and IFN-gamma, act through common regulatory elements to which
      different transcription factors sharing almost the same sequence specificity
      bind.

PMID- 7509447
TI  - The Drosophila micropia retrotransposon encodes a testis-specific antisense RNA
      complementary to reverse transcriptase.
AB  - The micropia transposable element of Drosophila hydei is a long terminal repeat
      containing retrotransposon present in both the autosomes and the Y chromosome.
      micropia expression gives rise to a complex set of sense and antisense RNAs
      transcribed primarily during spermatogenesis. The most abundant sense RNAs
      constitute an assortment of heterogeneous high-molecular-weight transcripts
      expressed as constituents of the Y-chromosomal lampbrush loops of primary
      spermatocytes. In addition, micropia encodes a full-length RNA that extends
      between the two long terminal repeats of the element. The major 1.0-kb antisense
      RNA characterized is complementary to the reverse transcriptase and RNase H
      coding regions of micropia. It is expressed from a testis-specific promoter
      during the primary spermatocyte stages and is detectable until spermatid
      elongation stages. Sequence comparison of this promoter with the 5' region of
      other testis-specific genes allows the conception of a conserved sequence that is
      responsible for this pattern of expression. A 284-bp fragment containing this
      sequence is able to drive testis-specific expression of the Escherichia coli lacZ
      gene in Drosophila melanogaster. This sequence is conserved in the micropia
      elements present in other Drosophila species that also encode an antisense RNA.
      The evolutionary conservation of micropia antisense RNA expression and the
      sequences responsible for its testis-specific transcription suggests a role for
      this antisense RNA in the control of germ line expression of the full-length
      transcript or transposon-encoded proteins.

PMID- 7509446
TI  - Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent
      binding of pp60src.
AB  - The phosphorylation of protein tyrosine kinases (PTKs) on tyrosine residues is a
      critical regulatory event that modulates catalytic activity and triggers the
      physical association of PTKs with Src homology 2 (SH2)-containing proteins. The
      integrin-linked focal adhesion kinase, pp125FAK, exhibits extracellular matrix
      dependent phosphorylation on tyrosine and physically associates with two
      nonreceptor PTKs, pp60src and pp59fyn, via their SH2 domains. Herein, we identify
      Tyr-397 as the major site of tyrosine phosphorylation on pp125FAK both in vivo
      and in vitro. Tyrosine 397 is located at the juncture of the N-terminal and
      catalytic domains, a novel site for PTK autophosphorylation. Mutation of Tyr-397
      to a nonphosphorylatable residue dramatically impairs the phosphorylation of
      pp125FAK on tyrosine in vivo and in vitro. The mutation of Tyr-397 to Phe also
      inhibits the formation of stable complexes with pp60src in cells expressing Src
      and FAK397F, suggesting that autophosphorylation of pp125FAK may regulate the
      association of pp125FAK with Src family kinases in vivo. The identification of
      Tyr-397 as a major site for FAK autophosphorylation provides one of the first
      examples of a cellular protein containing a high-affinity binding site for a Src
      family kinase SH2 domain. This finding has implications for models describing the
      mechanisms of action of pp125FAK, the regulation of the Src family of PTKs, and
      signal transduction through the integrins.

PMID- 7509448
TI  - Structural and functional aspects of the multiplicity of Neu differentiation
      factors.
AB  - We used molecular cloning and functional analyses to extend the family of Neu
      differentiation factors (NDFs) and to explore the biochemical activity of
      different NDF isoforms. Exhaustive cloning revealed the existence of six distinct
      fibroblastic pro-NDFs, whose basic transmembrane structure includes an
      immunoglobulin-like motif and an epidermal growth factor (EGF)-like domain.
      Structural variation is confined to three domains: the C-terminal portion of the
      EGF-like domain (isoforms alpha and beta), the adjacent juxtamembrane stretch
      (isoforms 1 to 4), and the variable-length cytoplasmic domain (isoforms a, b, and
      c). Only certain combinations of the variable domains exist, and they display
      partial tissue specificity in their expression: pro-NDF-alpha 2 is the
      predominant form in mesenchymal cells, whereas pro-NDF-beta 1 is the major
      neuronal isoform. Only the transmembrane isoforms were glycosylated and secreted
      as biologically active 44-kDa glycoproteins, implying that the transmembrane
      domain functions as an internal signal peptide. Extensive glycosylation precedes
      proteolytic cleavage of pro-NDF but has no effect on receptor binding. By
      contrast, the EGF-like domain fully retains receptor binding activity when
      expressed separately, but its beta-type C terminus displays higher affinity than
      alpha-type NDFs. Likewise, structural heterogeneity of the cytoplasmic tails may
      determine isoform-specific rate of pro-NDF processing. Taken together, these
      results suggest that different NDF isoforms are generated by alternative splicing
      and perform distinct tissue-specific functions.

PMID- 7509450
TI  - Methylation of single sites within the herpes simplex virus tk coding region and
      the simian virus 40 T-antigen intron causes gene inactivation.
AB  - In order to determine whether partial methylation of the herpes simplex virus
      (HSV) tk gene prevents tk gene expression, the HSV tk gene was cloned as single
      stranded DNA. By in vitro second-strand DNA synthesis, specific HSV tk gene
      segments were methylated, and the hemimethylated DNA molecules were microinjected
      into thymidine kinase-negative rat2 cells. Conversion of the hemimethylated DNA
      into symmetrical methylated DNA and integration into the host genome occurred
      early after gene transfer, before the cells entered into the S phase. HSV tk gene
      expression was inhibited either by promoter methylation or by methylation of the
      coding region. Using the HindIII-SphI HSV tk DNA fragment as a primer for in
      vitro DNA synthesis, all cytosine residues within the coding region, from +499 to
      +1309, were selectively methylated. This specific methylation pattern caused
      inactivation of the HSV tk gene, while methylation of the cytosine residues
      within the nucleotide sequence from +811 to +1309 had no effect on HSV tk gene
      activity. We also methylated single HpaII sites within the HSV tk gene using a
      specific methylated primer for in vitro DNA synthesis. We found that of the 16
      HSV tk HpaII sites, methylation of 6 single sites caused HSV tk inactivation. All
      six of these "methylation-sensitive" sites are within the coding region,
      including the HpaII-6 site, which is 571 bp downstream from the transcription
      start site. The sites HpaII-7 to HpaII-16 were all methylation insensitive. We
      further inserted separately the methylation-sensitive HSV tk HpaII-6 site and the
      methylation-insensitive HpaII-13 site as DNA segments (32-mer) into the intron
      region of the simian virus 40 T antigen (TaqI site). Methylation of these HpaII
      sites caused inhibition of simian virus 40 T-antigen synthesis.

PMID- 7509449
TI  - Expression of the v-crk oncogene product in PC12 cells results in rapid
      differentiation by both nerve growth factor- and epidermal growth factor
      dependent pathways.
AB  - The transforming gene of the avian sarcoma virus CT10 encodes a fusion protein
      (p47gag-crk or v-Crk) containing viral Gag sequences fused to cellular sequences
      consisting primarily of Src homology regions 2 and 3 (SH2 and SH3 sequences).
      Here we report a novel function of v-Crk in the mammalian pheochromocytoma cell
      line, PC12, whereby stable expression of v-Crk induces accelerated
      differentiation, as assessed by induction of neurites following nerve growth
      factor (NGF) or basic fibroblast growth factor (bFGF) treatment compared with the
      effect in native PC12 cells. Surprisingly, however, these cells also develop
      extensive neurite processes after epidermal growth factor (EGF) stimulation, an
      event which is not observed in native PC12 cells. Following EGF or NGF
      stimulation of the v-CrkPC12 cells, the v-Crk protein itself became tyrosine
      phosphorylated within 1 min. Moreover, in A431 cells or TrkA-PC12 cells, which
      overexpress EGF receptors and TrkA, respectively, a GST-CrkSH2 fusion protein was
      indeed capable of binding these receptors in a phosphotyrosine-dependent manner,
      suggesting that v-Crk can directly couple to receptor tyrosine kinase pathways in
      PC12 cells. In transformed fibroblasts, v-Crk binds to specific tyrosine
      phosphorylated proteins of p130 and paxillin. Both of these proteins are also
      complexed to v-Crk in PC12 cells, as evidenced by their coprecipitation with v
      Crk in detergent lysates, suggesting that common effector pathways may occur in
      both cell types. However, whereas PC12 cellular differentiation can occur solely
      by overexpression of the v-Src or oncogenic Ras proteins, that induced by v-Crk
      requires a growth factor stimulatory signal, possibility in a two-step process.

PMID- 7509455
TI  - Apoptosis. Fascinating death factor.

PMID- 7509453
TI  - Evaluation of Calcofluor staining in the diagnosis of fungal corneal ulcer.
AB  - For laboratory diagnosis of mycotic keratitis, demonstration of fungal pathogens
      on direct microscopy and their isolation by culture is essential. The addition of
      Calcofluor white (CFW) stain to the diagnostic armamentarium has significantly
      increased the sensitivity of smear examination on direct microscopy. During a
      period of 1 year, 143 consecutive patients with corneal ulcers were investigated
      by direct microscopy with potassium hydroxide (KOH) wet mount, Calcofluor white
      stain and routine cultures of corneal scrapings. Fungi were detected as
      aetiological agents in 21 (15%) patients. Different species of the genera
      Aspergillus (35%), Fusarium (23%), Acremonium (12%), Paecilomyces (12%),
      Cladosporium (6%), Alternaria (6%) and Pseudallescheria (6%) were the common
      isolates. Calcofluor white stain on direct microscopy detected fungi in 20
      (95.2%) patients in comparison with 15 (71.4%) patients by both KOH wet mount
      examination and culture. Calcofluor white stain was significantly more sensitive
      than KOH wet mount in demonstrating fungal pathogens.

PMID- 7509452
TI  - Rapid microscopical diagnosis of deep-seated mycoses following maceration of
      fresh specimens and staining with optical brighteners.
AB  - A fluorescent staining procedure, which used to be recommended for the detection
      of fungi in skin and nail scrapings, can be adapted for the rapid detection of
      fungal elements in non-sectioned biopsies or respiratory secretions. The
      specimens are directly stained with an optical brightener (Blankophor P flussig,
      Cellufluor, Uvitex 2B) preferentially after exposure to 20% aqueous potassium
      hydroxide solution. The procedure can also be applied to Gram-stained microscopic
      mounts. The high intensity of the fluorescence elicited allows rapid microscopic
      screening at low magnifications.

PMID- 7509454
TI  - Simultaneous demonstration of infecting fungi and DNA-synthesizing epithelial
      cells in the skin.
AB  - An excellent staining method to demonstrate in vivo dermatophytes and DNA
      synthesizing cells in the skin is described. Deparaffinized sections of guinea
      pig skin, infected with dermatophytes and given bromodeoxyuridine (BrdU) by
      intraperitoneal injection, were used. Periodic acid-Schiff (PAS) stain in
      combination with an immunohistochemical stain using anti-BrdU monoclonal antibody
      allowed simultaneous visualization of fungi and DNA-synthesizing epithelial cells
      in the skin. Many epithelial cells near the infecting fungi in follicles and
      interfollicular skin were labelled with BrdU. Only a few BrdU-positive cells were
      observed in the skin of uninfected animals.

PMID- 7509451
TI  - Growth hormone and erythropoietin differentially activate DNA-binding proteins by
      tyrosine phosphorylation.
AB  - Binding of growth hormone (GH) and erythropoietin (EPO) to their respective
      receptors results in receptor clustering and activation of tyrosine kinases that
      initiate a cascade of events resulting not only in the rapid tyrosine
      phosphorylation of several proteins but also in the induction of early-response
      genes. In this report, we show that GH and EPO induce the tyrosine
      phosphorylation of cellular proteins with molecular masses of 93 kDa and of 91
      and 84 kDa, respectively, and that these proteins form DNA-binding complexes
      which recognize an enhancer that has features in common with several rapidly
      induced genes such as c-fos. Assembly of the protein complexes required tyrosine
      phosphorylation, which occurred within minutes after addition of ligand. The
      activated complexes translocated from the cytoplasm to the nucleus. The protein
      activated by GH is antigenically similar to p91, a protein common to several
      transcription complexes that are activated by interferons and other cytokines. In
      contrast, the proteins activated by EPO are distinct from p91. These findings
      establish the outlines for a cytokine-induced intracellular signaling pathway,
      which begins with ligand-induced receptor clustering that activates one or more
      tyrosine kinases. These data are the first to demonstrate that GH- and EPO
      activated tyrosine-phosphorylated proteins can specifically recognize a well
      defined enhancer and therefore provide a mechanism for rapidly transducing
      signals from the membrane to the nucleus.

PMID- 7509456
TI  - Materials science. Polymers made to measure.

PMID- 7509457
TI  - Dissolve and capture: a strategy for analysing mRNA in blood.
AB  - Messenger RNA (mRNA) sequences were amplified from whole blood prepared in
      guanidine thiocyanate (GuSCN) after capture of the mRNA with an affinity
      membrane.

PMID- 7509458
TI  - Control of tachykinin-evoked acetylcholine release from rat striatal slices by
      dopaminergic neurons.
AB  - The regulation of tachykinin-evoked acetylcholine release by the dopaminergic
      system in the neostriatum was examined. We studied the effect of selective and
      potent tachykinin agonists for each subtype of receptor ([Sar9,Met(O2)11]
      Substance P for NK1; [Nle10]-Neurokinin A4-10 for NK2; and senktide for NK3) on
      endogenous acetylcholine release from rat striatal slices where the dopaminergic
      system was modified either by 6-hydroxydopamine lesion or by dopamine receptor
      antagonists. Unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway
      induced a decrease in senktide-evoked acetylcholine release and an increase in
      the effect of [Nle10]-Neurokinin A4-10. The same results were obtained after
      chronic haloperidol treatment, whereas SCH-23390 or clozapine treatment had no
      effect on tachykinin-evoked acetylcholine release, suggesting an involvement of
      D2 receptors. 6-hydroxydopamine lesion induced a diminution in the density of NK3
      receptor, which could be related to the reduction in senktide-evoked
      acetylcholine release.

PMID- 7509459
TI  - Azelastine and allergen transduction signal in MC9 mast cells.
AB  - MC9 mast cells, sensitized with monoclonal IgE antibody specific for 2,4
      dinitrophenyl (DNP) group, were exposed to DNP-BSA and the pH and cytosolic
      calcium signals were recorded by using the fluorescent probes BCECF and Fura-2
      respectively. DNP-BSA induced cell alkalinization was fully inhibited by
      azelastine with IC50 (1.6 +/- 0.5 mumol/l, mean +/- SEM, n = 5) similar to that
      required to inhibit histamine release (1.4 mumol/l). Conversely, high azelastine
      concentrations (> 100 mumol/l) were required to inhibit DNP-BSA-dependent cell
      calcium mobilization (IC50 approximately 200 mumol/l, n = 3). Amiloride, but not
      the H1 histamine antagonist pyrilamine, was able to inhibit the DNP-BSA induced
      pH signal. In acidified mast cells, azelastine potently inhibited Na+:H+ exchange
      activity (IC50 = 7.7 +/- 3.6 x 10(-6) M, mean +/- SEM, n = 3). Conversely, in
      mouse spleen lymphocytes azelastine was unable to inhibit the amiloride-sensitive
      pH signal induced by concanavalin A. In conclusion, the inhibition of histamine
      release by azelastine is not due to an interference with the cytosolic calcium
      signal. Conversely, azelastine potently antagonized the allergen-dependent Na+:H+
      exchange activation, suggesting an action on the protein kinase C signaling
      pathway.

PMID- 7509462
TI  - [A case report of interstitial pneumonia caused by granulocyte colony-stimulating
      factor].
AB  - Several clinical trials have demonstrated that granulocyte colony-stimulating
      factor (G-CSF) accelerates the recovery of neutropenia in chemotherapy-induced
      bone marrow suppression. In this report, we describe a 46-year-old female with
      glioblastoma multiforme who developed interstitial pneumonia due to
      administration of G-CSF during the phase of immunochemoradiotherapy-induced
      neutropenia. Thirty-three days after starting immunochemoradiotherapy (ACNU, VCR,
      IFN -beta, radiation), she developed neutropenia (1,000/microliters).
      Administration of G-CSF at doses of 125-250 micrograms/day led to an increase of
      peripheral neutrophil counts. Eleven days later, the patient developed sudden
      severe respiratory failure and cyanosis with worsening of lung shadows. Blood gas
      levels on room air were PaO2 49.3mmHg, PaCO2 28.0mmHg, and pH 7.46. At this time,
      her neutrophil count had risen to 26,080/microliters. LDH and alpha - HBD had
      also increased to 1,439 IU/l and 1,117IU/l respectively. Chest radiograph and CT
      scan demonstrated interstitial pneumonia. After treatment with methyl
      prednisolone, her respiratory symptoms were gradually resolved. A number of side
      effects have been reported with granulocyte-macrophage colony-stimulating factor
      (GM-CSF). These include fluid retention with pericardial and pleural effusion,
      fever, bone pain, fatigue, and rash. This report also suggests that G-CSF might
      be a cause of interstitial pneumonia during the phase of immunochemoradiotherapy
      induced neutropenia.

PMID- 7509461
TI  - [Myelin basic protein in the cerebrospinal fluid of patients with neurological
      disease: especially with malignant brain tumors].
AB  - Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with
      brain tumors and other neurological diseases was measured before, during and
      after various treatments such as surgery, chemotherapy and irradiation. We
      assessed the significance of changes in the MBP levels during the course of
      treatment, and speculate on what the elevated level of MBP in brain tumor
      patients indicates. In meningeal dissemination of malignant tumors, meningeal
      carcinomatosis from cancer of the systemic organ showed the highest level of MBP
      followed by meningeal gliomatosis and meningeal lymphoma. Meningeal
      carcinomatosis and meningeal lymphoma, which have responded to chemotherapy,
      showed normal levels of MBP after chemotherapy. Six of eight patients with newly
      diagnosed malignant glioma showed moderate to high levels of MBP (range 4.6
      35.5ng/ml) just before intraarterial chemotherapy with VP-16 and CDDP. The level
      increased in five patients during the course of chemotherapy and then decreased
      in relation to the degree of tumor reduction by chemotherapy. In the solid type
      of metastatic brain tumor, five of seven patients with multiple tumors showed
      high levels of MBP and these levels also returned to normal after treatment in
      four patients. As for the influence of irradiation, levels of MBP did not
      increase after irradiation except in three patients who developed radiation
      necrosis, local extensive edema or atrophic change. In other brain tumors, levels
      of MBP were high in a patient with a large meningioma with very extensive edema
      and during an unstable postoperative condition after total removal of a large
      craniopharyngioma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509460
TI  - The immunosuppressive drugs cyclosporin A and FK506 inhibit calcineurin
      phosphatase activity and gene transcription mediated through the cAMP-responsive
      element in a nonimmune cell line.
AB  - Cyclosporin A and the macrolide tacrolimus (FK506) are powerful immunosuppressive
      drugs that in T cells inhibit the calcium/calmodulin-dependent phosphatase
      calcineurin thereby preventing the activation of T-cell-specific transcription
      factors, such as NF-AT, involved in lymphokine gene expression. While this may
      explain, at least in part, the mechanism of cyclosporin A/FK506
      immunosuppression, additional mechanisms have to be invoked in order to explain
      the pharmacological properties and toxic effects of these drugs, such as
      nephrotoxicity and neurotoxicity. We have studied the effects of cyclosporin A
      and FK506 on calcineurin phosphatase activity and gene transcription mediated by
      the cAMP-responsive element (CRE), a binding site of the ubiquitous transcription
      factor CREB. A reporter gene was placed under the transcriptional control of the
      CRE of the rat glucagon gene and transiently transfected into the glucagon
      expressing cell line alpha TC2. Cyclosporin A and FK506 inhibited depolarization
      induced gene transcription in a concentration-dependent manner (IC50 of about 1
      nM and 30 nM for FK506 and cyclosporin A, respectively). Both cyclosporin A and
      FK506 inhibited calcineurin phosphatase activity at drug concentrations that
      inhibited gene transcription. The FK506 analogue rapamycin had no effect on
      calcineurin activity and gene transcription, but excess concentrations of
      rapamycin prevented the effects of FK506 on both calcineurin activity and gene
      transcription. These results support the notion that the interaction of drug
      immunophilin complexes with calcineurin may be the molecular basis of cyclosporin
      A/FK506-induced inhibition of CREB/CRE-mediated gene transcription. The ability
      to interfere with CREB/CRE-mediated gene transcription represents a novel
      mechanism of cyclosporin A/FK506 action which may underlie pharmacological
      effects and toxic manifestations of these potent immunuosuppressive drugs.

PMID- 7509463
TI  - Effect of progesterone on galanin mRNA levels in the hypothalamus and the
      pituitary: correlation with the gonadotropin surge.
AB  - Galanin has been shown to be an important neuropeptide associated with the
      preovulatory surge of gonadotropins. Since the preovulatory surge of
      gonadotropins is induced by the action of estrogens and progesterone, the present
      study examined the effect of estrogens and progesterone on hypothalamic and
      pituitary galanin mRNA levels. Galanin mRNA was present as the 900-base pair
      message in the hypothalamus and the pituitary. In the 27-day-old ovariectomized
      immature rat, treatment with 2 micrograms of estradiol for 2 days did not bring
      about any changes in hypothalamic galanin mRNA levels. In adult rats, ovariectomy
      also did not bring about any changes in hypothalamic galanin mRNA levels.
      However, 14 days of estradiol replacement increased hypothalamic galanin mRNA
      levels. Progesterone treatment in the estrogen-primed ovariectomized immature rat
      resulted in a significant increase in hypothalamic galanin mRNA levels at 12:00
      and 14:00 h. This increase occurred at the time of the initiation of the
      progesterone-induced LH and FSH surges. Estrogen treatment enhanced pituitary
      galanin mRNA levels which were further increased by progesterone treatment at
      12:00 h, the time of the initiation of the gonadotropin surge by progesterone. In
      the PMSG-primed immature rat, pituitary galanin mRNA levels were increased due to
      ovarian estrogen and progesterone secretion as a result of PMSG treatment.
      Pituitary galanin mRNA levels were decreased by the anti-progestin RU486 at 12:00
      and 20:00 h, times that coincided with a decrease in serum LH by RU486 as
      compared to the PMSG-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509464
TI  - Effects of hypophysectomy on galaninergic neurons in the rat hypothalamus.
AB  - To understand better the relationship between hypothalamic galaninergic neurons
      and the pituitary gland, we studied the effects of hypophysectomy on hypothalamic
      galanin (GAL) content and distribution by radioimmunoassay and
      immunohistochemistry, and on GAL mRNA by Northern blot analysis. Three weeks
      after hypophysectomy, performed at 5 or 8 weeks of age, the hypothalamic
      concentrations of GAL and GAL mRNA were reduced by 30-50% in both male and female
      rats, compared to age- and sex-matched controls. Similar reverse-phase HPLC
      retention times of hypothalamic GAL were observed in intact and hypophysectomized
      rats. The reduction of hypothalamic GAL concentration following hypophysectomy
      was time-dependent, as peptide levels were unaffected one week after surgery.
      Immunohistochemistry showed regional differences in the effect of hypophysectomy
      on galaninergic neurons. In the hypophysiotropic hypothalamus, the scarce GAL
      immunoreactivity normally observed in the arcuate nuclei was no longer detectable
      in hypophysectomized rats, and the intense GAL immunoreactivity of the external
      zone of the median eminence progressively decreased and completely disappeared 3
      and 6 weeks after hypophysectomy. In contrast, in the neurohypophyseal system,
      there was an increase of GAL labelling of the perikarya and emerging axons in the
      supraoptic and lateral-paraventricular nuclei, 1 and 3 weeks after
      hypophysectomy, that disappeared 6 weeks after hypophysectomy. An increase of GAL
      immunoreactivity was also observed in the internal zone of the median eminence 1
      week but not 3 weeks after hypophysectomy. We conclude that hypophysectomy
      reduces the content of GAL and GAL mRNA in the rat hypothalamus. These changes
      are time-dependent and clearly detected after 3 weeks. The neurohypophyseal and
      hypophysiotropic galaninergic systems respond differently to
      hypophysectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509466
TI  - Inhaled substance P induces activation of alveolar macrophages and increases
      airway responses in the guinea-pig.
AB  - Guinea-pigs pretreated with phosphoramidon or saline were treated with an aerosol
      of substance P (SP) or saline. 24 h later, the pulmonary inflation pressure (PIP)
      to substance P or to cumulative doses of acetylcholine or of histamine was
      recorded. The PIP response to SP itself was significantly enhanced in animals
      treated with phosphoramidon+SP as compared with phosphoramidon+saline (2.5-fold
      increase 1 min after the end of the inhalation, P < 0.001). The response to
      acetylcholine and to histamine was also significantly enhanced in
      phosphoramidon+substance P-treated as compared with phosphoramidon+saline-treated
      guinea-pigs (PC200 = 38.9 and 1.6 as compared with 77.6 and 3.9 micrograms/ml, P
      < 0.01 and P < 0.05 respectively). The production of superoxide anions by
      alveolar macrophages in response to f-MLP was also enhanced after treatment with
      phosphoramidon+SP as compared with phosphoramidon+saline (6.4 +/- 0.7 and 3.8 +/-
      0.3 cpm, P < 0.001 respectively). In animals treated with saline+SP or
      saline+saline, the PIP responses and the production of superoxide anion were
      similar. Altogether these results suggest that SP contributes to the bronchial
      hyper-responsiveness in asthma and this probably through activation of alveolar
      macrophages.

PMID- 7509465
TI  - Characterization of vascular postsynaptic NPY receptor function and regulation
      and differential sensitivity of Y1 and Y2 receptor function to changes in
      extracellular calcium availability and prior in vitro peptide exposure.
AB  - Effects of calcium-free buffer, nifedipine, or prior cumulative neuropeptide Y
      (NPY) receptor agonist concentration exposure on vasoconstrictive responsiveness
      to the agonists were assessed in norepinephrine (NE)-conditioned isolated rat
      femoral artery rings. Calcium-free buffer and nifedipine partially inhibited
      responsiveness to initial NPY exposure; residual responsiveness to NPY re
      exposure was unaffected. In contrast, these treatments markedly inhibited
      responsiveness to the Y2 agonist NPY13-36, the calcium channel agonist BAY K 8644
      (BAY) and the partial alpha 1 adrenoceptor agonist indanidine but did not alter
      to the Y1 agonist [Leu31,Pro34]NPY. Responsiveness to NPY and NPY13-36 but not to
      BAY or indanidine was markedly reduced 120 min following conditioning regardless
      of prior ring exposure to the same peptide; only prior exposure reduced
      responsiveness to [Leu31,Pro34]NPY. Responsiveness changes to NPY at various
      times or after various numbers of NE and/or NPY exposures indicated that pre
      exposure and time-related responsiveness reductions were discriminable and
      temporally unrelated to conditioning. Postsynaptic vascular Y2 receptor
      activation therefore accounts for the known sensitivity of NPY-induced pressor
      and vasoconstrictive actions to nifedipine. The 'time-dependent' loss of Y2
      receptor function may also explain prior failures to observe postsynaptic
      arterial Y2 receptors in vitro.

PMID- 7509467
TI  - Ultrastructural studies on peptides in the dorsal horn of the spinal cord--I. Co
      existence of galanin with other peptides in primary afferents in normal rats.
AB  - The aim of the present study was to investigate galanin-like immunoreactivity in
      primary afferent terminals and its relationship to other neuropeptides in laminae
      I and II of the fourth and fifth lumbar segments of normal rat spinal cord using
      immunofluorescence and pre- and post-embedding electron-microscopic
      immunocytochemistry. Triple-immunofluorescence staining showed that galanin-like
      immunoreactivity co-localized with substance P- and calcitonin gene-related
      peptide-like immunoreactivities in many nerve fibres and terminals in laminae I
      and II of the dorsal horn. At the ultrastructural level, using pre-embedding
      immunocytochemistry, galanin-like immunoreactivity was found in type I glomeruli
      with an electron-dense central terminal containing many densely packed synaptic
      vesicles and several large dense-core vesicles. Both the cytoplasm and the core
      of the large vesicles were immunoreactive. In type II glomeruli with an electron
      lucent central terminal and loosely packed synaptic vesicles the large dense-core
      vesicles and the cytoplasm were only weakly galanin-positive. Post-embedding
      immunocytochemistry revealed that galanin-like immunoreactivity co-existed with
      substance P- and calcitonin gene-related peptide-like immunoreactivities in many
      terminals and in individual large dense-core vesicles in lamina II. These
      terminals were considered to represent primary afferents, since there is evidence
      that calcitonin gene-related peptide in the dorsal horn only occurs in nerve
      endings originating in dorsal root ganglia. Evidence was also unexpectedly
      obtained for the occurrence of several other peptides in calcitonin gene-related
      peptide-positive terminals, i.e. in presumably primary afferents. Thus galanin
      like immunoreactivity sometimes also co-localized with cholecystokinin- and
      neuropeptide tyrosine-like immunoreactivities in calcitonin gene-related peptide
      immunoreactive terminals and in some large dense-core vesicles in such terminals.
      A small number of calcitonin gene-related peptide immunoreactive, presumably
      primary afferent terminals contained enkephalin-, neurotensin- (and galanin-)like
      immunoreactivities. These results indicated that galanin can be co-stored with
      several other neuropeptides in large dense-core vesicles in primary afferent
      terminals and may presumably be released together with them in the superficial
      layer of the dorsal horn. Since various combinations of peptides, presumably at
      varying concentrations, occur in the large dense-core vesicles in a given nerve
      ending, it is likely that the individual large dense-core vesicles produced in a
      neuron are heterogenous with regard to peptide content and thus to the message
      that they transmit upon release.

PMID- 7509468
TI  - Time-dependent changes in Bolton-Hunter-labeled 125I-substance P binding in rat
      spinal cord following unilateral adjuvant-induced peripheral inflammation.
AB  - Time-dependent changes in Bolton-Hunter-labeled 125I-substance P binding occurred
      in the dorsal horn of the spinal cord following unilateral adjuvant-induced
      inflammation in the hindpaw of the rat. Inflammation was characterized by
      measures of edema and hyperalgesia. Edema and hyperalgesia were both present 6 h
      after induction of inflammation. However, by eight days, hyperalgesia had
      dissipated while edema persisted. Six hours after the induction of inflammation,
      widespread decreases in Bolton-Hunter-labeled 125I-substance P binding occurred
      on both sides of the dorsal horn of spinal level L4 in comparison to the control
      group. However, by two days, widespread increases in Bolton-Hunter-labeled 125I
      substance P binding occurred on both sides of the spinal cord at level L4
      compared to the control group. The increase in radioligand binding was primarily
      due to a 10-fold increase in affinity of neurokinin-1 receptors for substance P.
      At later time-points of four and eight days, Bolton-Hunter-labeled 125I-substance
      P binding remained increased only in laminae I/II on the side of the spinal cord
      ipsilateral to inflammation. The changes in Bolton-Hunter-labeled 125I-substance
      P binding suggest that alterations in substance P synaptic transmission in the
      spinal cord may contribute to the increased excitability of spinal neurons that
      accompanies adjuvant-induced peripheral inflammation.

PMID- 7509470
TI  - Effect of cocaine on macromolecular syntheses and cell proliferation in cultured
      glial cells.
AB  - In the present study the effect of cocaine on thymidine, uridine and leucine
      incorporation was assessed in primary cortical glial and C6 glioma cells. Cocaine
      exposure for 24 h inhibited thymidine and uridine incorporation in cortical glial
      and C6 glioma cells. However, the effect of cocaine on uridine incorporation was
      less prominent compared to thymidine incorporation. High concentrations of
      cocaine inhibited leucine incorporation in C6 glioma cells but not in cortical
      glia. Cocaine exposure for four days decreased cell proliferation of cortical
      glial and C6 glioma cells. Cocaine-induced attenuation of macromolecular
      syntheses was not due to cell death since cocaine-treated cells were not stained
      with Trypan Blue and did not release lactate dehydrogenase into culture
      supernatants. Furthermore, cocaine had no effect on glutamate uptake either in
      cortical glia or in C6 glioma cells. These results indicate that cocaine inhibits
      macromolecular syntheses in glial cells. The inhibition of macromolecular
      syntheses in glial cells may be the mechanism involved in cocaine-induced fetal
      brain growth retardation.

PMID- 7509471
TI  - Indocyanine green angiography and occult choroidal neovascularization.
AB  - PURPOSE: To evaluate the use of digital indocyanine green (ICG) angiography as an
      adjunct to fluorescein angiography in the diagnosis and treatment of ill-defined
      choroidal neovascularization (CNV) associated with age-related macular
      degeneration (AMD). METHODS: The authors retrospectively reviewed all ICG
      angiograms performed at Wills Eye Hospital from March to July 1992. Included in
      this study were all cases with exudative manifestations of AMD in which
      fluorescein angiography showed ill-defined CNV. The initial ICG findings and the
      clinical outcome of both treated and untreated cases were evaluated through 6
      months of follow-up. RESULTS: Of the 101 eligible cases, ICG angiography at
      presentation demonstrated well-defined hyperfluorescence in 40 cases (group 1),
      ill-defined hyperfluorescence in 43 cases (group 2), mixed pattern of well- and
      ill-defined hyperfluorescence in 14 cases (group 3), and no abnormalities in 4
      cases (group 4). Approximately one half of the cases with well-defined ICG
      hyperfluorescence (21% of the total) had only extrafoveal changes. Laser
      photocoagulation treatment based solely on ICG angiogram findings was performed
      in 19 group 1 cases (extrafoveal hyperfluorescent foci only) and in 8 group 3
      cases, with treatment in both groups being directed only to areas of well-defined
      hyperfluorescence. Successful treatment was achieved in 12 (63%) of 19 cases and
      in 2 (25%) of 8 cases, respectively. There was a strong correlation between post
      treatment persistence or recurrence of ICG hyperfluorescence and treatment
      failure. CONCLUSIONS: Indocyanine green angiography is a valuable diagnostic
      adjunct to fluorescein angiography in evaluating occult CNV in AMD. In this
      series, well-defined, extrafoveal ICG hyperfluorescence was identified in 21% of
      the cases, and preliminary, short-term results suggest that ICG-guided laser
      treatment is promising in this subgroup.

PMID- 7509469
TI  - Different responses to opioids measured in terminals and somas of Edinger
      Westphal neurons.
AB  - Neurotransmitter receptors on the axon terminals of a neuron can be located a
      considerable distance away from comparable receptors on the cell body or
      dendrites of the same neuron. We examined the effects of activating either nerve
      terminal receptors or those located on or near the somas of chick Edinger
      Westphal neurons. Cell body responses were measured via intracellular recording
      in a brain slice preparation. To measure nerve terminal responses, intracellular
      recordings were obtained from the large, calyciform nerve endings in intact
      ciliary ganglia, which emanate from neurons of the lateral Edinger-Westphal
      nucleus. Cell bodies of Edinger-Westphal neurons responded to leucine-enkephalin
      with a dose-dependent hyperpolarization that was associated with a decrease in
      input resistance. In spontaneously active Edinger-Westphal somas, leucine
      enkephalin caused marked inhibition of suprathreshold and subthreshold activity,
      indicating that, as with a number of other central neurons, the major effect of
      opioids was to reduce excitability. The response to opioids was sensitive to
      naloxone (1 microM) and was a direct effect, since it was not blocked by either
      0.5 microM tetrodotoxin or 100 microM cadmium. More selective mu ([D-Ala2, N-Me
      Phe4, Gly5-ol]-enkephalin) and delta ([D-Ser2]-leucine-enkephalin-Thr and [D
      Pen2,5]-enkephalin) opioid agonists produced effects similar to those of leucine
      enkephalin. Opioids produced strikingly different effects in the nerve terminals
      of Edinger-Westphal neurons, where the major effect was a depolarization
      associated with a decrease in input resistance. The effects of opioids in the
      terminals were reduced in a low sodium buffer, indicating that they were
      dependent on the presence of extracellular sodium.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7509472
TI  - The treatment of choroidal neovascular membranes by alpha interferon. An efficacy
      and toxicity study.
AB  - PURPOSE: The purpose of this phase 2 study was to determine the potential
      efficacy and safety of systemic alpha interferon in the treatment of subfoveal
      choroidal neovascularization associated with age-related macular degeneration or
      ocular histoplasmosis. METHOD: Subcutaneous alpha interferon was administered to
      24 patients (24 eyes), and they were prospectively studied. Alpha interferon was
      administered subcutaneously four times daily at a dose of 3 x 10(6) U/m2 (average
      total dose, 204 MU). The studied parameters included best-corrected visual
      acuity, membrane size, blood, exudates, and subretinal fluid. Toxic effects and
      performance status were graded according to the National Cancer Institute
      toxicity criteria and Karnofsky performance scale, respectively. RESULTS: Of the
      24 treated eyes, 5 (21%) showed objective evidence of anatomic improvement, as
      defined by decrease in membrane size or improvement in fluorescein angiographic
      characteristics, but in only 3 of these 5 was the improvement maintained. The
      same three patients achieved and maintained functional success (visual
      improvement). Two of the five patients with initial anatomic improvement had
      subsequent membrane recurrence, which resulted in no visual change in one but
      visual loss in the other. For the majority of patients, the anatomic and visual
      status remained the same or became worse after treatment. All patients
      experienced some degree of adverse reactions involving multiple organ systems.
      Decreased performance status affected 80% of the patients. CONCLUSION: This study
      documents that regression of choroidal neovascularization that occurred with
      alpha interferon treatment was minimal. Toxic effects interfering with patients'
      performance status are associated with alpha interferon treatment. Although a
      randomized trial of interferon versus no therapy may be warranted, fundamental
      issues (i.e., the biologic properties of interferon versus other more potent
      agents against choroidal neovascularization, medication dosages, and routes of
      administration), need to be addressed before embarking on such a trial.

PMID- 7509473
TI  - Utilization of cofactors expands metabolism in a new RNA world.
AB  - RNA has been hypothesized to have preceded proteins as the major catalysts of the
      biosphere, yet there are only a very limited number of chemical reactions that
      are known to be catalyzed by modern RNA. Cofactors are used by the majority of
      protein enzymes to supply additional functional groups to the active site. RNA
      should also be able to utilize some of these same cofactors to extend its own
      catalytic potential. We describe here how it could be possible to use selection-
      amplification from a population of random RNA to obtain a coenzyme A mediated RNA
      transacylase. Exploitation of some of the sulphur chemistry mediated by coenzyme
      A could have significantly expanded a prebiotic RNA directed metabolism.

PMID- 7509474
TI  - N6-substituted adenine derivatives and RNA primitive catalysts.
AB  - In our search for primitive RNA catalysts, we noticed that N6-ribosyl-adenine, a
      compound easily synthesized under presumed prebiotic conditions, has a free
      imidazole group. We showed that it is, as a catalyst, a potential analogue of
      histidine. Furthermore, among the chemical groups involved in protein catalysis,
      the imidazole ring of histidine has no equivalent in the RNA world. We have
      synthesized aliphatic amino groups containing polymers with adenine rings linked
      to macromolecules by their 6-amino group. These polymers exhibit pronounced
      catalytic activities in the hydrolysis of p-nitrophenylacetate. We discuss here
      the fact that in primitive catalysis the imidazole group could have been replaced
      by N6-substituted adenine derivatives.

PMID- 7509476
TI  - The RNA-world and co-evolution hypotheses and the origin of life: implications,
      research strategies and perspectives.
AB  - The applicability of the RNA-world and co-evolution hypotheses to the study of
      the very first stages of the origin of life is discussed. The discussion focuses
      on the basic differences between the two hypotheses and their implications, with
      regard to the reconstruction methodology, ribosome emergence, balance between
      ribozymes and protein enzymes, and their major difficulties. Additional
      complexities of the two hypotheses, such as membranes and the energy source of
      the first reactions, are not treated in the present work. A central element in
      the proposed experimental strategies is the study of the catalytic activities of
      very small peptides and RNA-like oligomers, according to existing, as well as to
      yet-to-be-invented scenarios of the two hypotheses under consideration. It is
      suggested that the novel directed molecular evolution technology, and molecular
      computational modelling, can be applied to this research. This strategy is
      assumed to be essential for the suggested goal of future studies of the origin of
      life, namely, the establishment of a 'Primordial Darwinian entity'.

PMID- 7509477
TI  - Experimental investigation of an RNA sequence space.
AB  - Modern rRNAs are the historic consequence of an ongoing evolutionary exploration
      of a sequence space. These extant sequences belong to a special subset of the
      sequence space that is comprised only of those primary sequences that can validly
      perform the biological function(s) required of the particular RNA. If it were
      possible to readily identify all such valid sequences, stochastic predictions
      could be made about the relative likelihood of various evolutionary pathways
      available to an RNA. Herein an experimental system which can assess whether a
      particular sequence is likely to have validity as a eubacterial 5S rRNA is
      described. A total of ten naturally occurring and hence known to be valid,
      sequences and two point mutants of unknown validity were used to test the
      usefulness of the approach. Nine of the ten valid sequences tested positive
      whereas both mutants tested as clearly defective. The tenth valid sequence gave
      results that would be interpreted as reflecting a borderline status were the
      answer not known. These results demonstrate that it is possible to experimentally
      determine which sequences in local regions of the sequence space are potentially
      valid 5S rRNAs. This approach will allow direct study of the constraints
      governing RNA evolution and allow inquiry into how the last common ancestor of
      extant life apparently came to have very complex ribosomal RNAs that subsequently
      were very conserved.

PMID- 7509478
TI  - RNA based evolutionary optimization.
AB  - The notion of an RNA world has been introduced for a prebiotic scenario that is
      dominated by RNA molecules and their properties, in particular their capabilities
      to act as templates for reproduction and as catalysts for several cleavage and
      ligation reactions of polynucleotides and polypeptides. This notion is used here
      also for simple experimental assays which are well suited to study evolution in
      the test tube. In molecular evolution experiments fitness is determined in
      essence by the molecular structures of RNA molecules. Evidence is presented for
      adaptation to environment in cell-free media. RNA based molecular evolution
      experiments have led to interesting spin-offs in biotechnology, commonly called
      'applied molecular evolution', which make use of Darwinian trial-and-error
      strategies in order to synthesize new pharmacological compounds and other
      advanced materials on a biological basis. Error-propagation in RNA replication
      leads to formation of mutant spectra called 'quasispecies'. An increase in the
      error rate broadens the mutant spectrum. There exists a sharply defined threshold
      beyond which heredity breaks down and evolutionary adaptation becomes impossible.
      Almost all RNA viruses studied so far operate at conditions close to this error
      threshold. Quasispecies and error thresholds are important for an understanding
      of RNA virus evolution, and they may help to develop novel antiviral strategies.
      Evolution of RNA molecules can be studied and interpreted by considering
      secondary structures. The notion of sequence space introduces a distance between
      pairs of RNA sequences which is tantamount to counting the minimal number of
      point mutations required to convert the sequences into each other. The mean
      sensitivity of RNA secondary structures to mutation depends strongly on the base
      pairing alphabet: structures from sequences which contain only one base pair (GC
      or AU are much less stable against mutation than those derived from the natural
      (AUGC) sequences. Evolutionary optimization of two-letter sequences in thus more
      difficult than optimization in the world of natural RNA sequences with four
      bases. This fact might explain the usage of four bases in the genetic language of
      nature. Finally we study the mapping from RNA sequences into secondary structures
      and explore the topology of RNA shape space. We find that 'neutral paths'
      connecting neighbouring sequences with identical structures go very frequently
      through entire sequence space. Sequences folding into common structures are found
      everywhere in sequence space.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7509475
TI  - Catalysis and prebiotic RNA synthesis.
AB  - The essential role of catalysis for the origins of life is discussed. The status
      of the prebiotic synthesis of 2',5'- and 3',5'-linked oligomers of RNA is
      reviewed. Examples of the role of metal ion and mineral catalysis in RNA oligomer
      formation are discussed.

PMID- 7509480
TI  - Prevalence and health impact of developmental disabilities in US children.
AB  - OBJECTIVE: Data from the 1988 National Health Interview Survey--Child Health
      Supplement were used to examine the prevalence of selected developmental
      disabilities and their impact among children ages 0 through 17 years. DESIGN: The
      following conditions, identified through a structured in-person interview with a
      parent or other adult household member, were examined: deafness or trouble
      hearing, blindness, epilepsy or seizures, stammering and stuttering, other speech
      defects, cerebral palsy, delay in growth or development, learning disabilities,
      and emotional or behavioral problems. The impact was defined by measures of
      perceived health status, school performance and attendance, and health care
      utilization. RESULTS: Seventeen percent of children in the United States were
      reported to have ever had a developmental disability. The prevalence of the
      individual disabilities ranged from 0.2% for cerebral palsy to 6.5% for learning
      disabilities. These conditions taken together had a substantial impact on the
      health and educational functioning of affected children: 1.5 times more doctor
      visits, 3.5 times more hospital-days, twice the number of school-days lost, and a
      2.5-fold increase in the likelihood of repeating a grade in school compared with
      children without these conditions. The extent of this impact was much greater
      among children with multiple disabilities or with either cerebral palsy, epilepsy
      or seizures, delays in growth and development, or emotional or behavioral
      problems. The impact on school performance was most pronounced for children
      reported to have learning disabilities. CONCLUSIONS: Future research efforts
      should be focused on ways to reduce the impact of these developmental
      disabilities on quality of life.

PMID- 7509479
TI  - On concerted origin of transfer RNAs with complementary anticodons.
AB  - Pairs of antiparallely oriented consensus tRNAs with complementary anticodons
      show surprisingly small numbers of mispairings within the 17-bp- long anticodon
      stem and loop region. Even smaller such complementary distances are shown by
      illegitimately complementary anticodons, i.e. those with allowed pairing between
      G and U bases. Accordingly, we suppose that transfer RNAs have emerged
      concertedly as complementary strands of primordial double helix-like RNA
      molecules. Replication of such molecules with illegitimately complementary
      anticodons might generate new synonymous codons for the same pair of amino acids.
      Logically, the idea of tRNA concerted origin dictates very ancient establishment
      of direct links between anticodons and the type of amino acids with which pre
      tRNAs were to be charged. More specifically, anticodons (first of all, the 2nd
      base) could selectively target 'their' amino acids, reaction of acylating itself
      being performed by another non-specific site of pre-tRNA or even by another
      ribozyme. In all, the above findings and speculations are consistent to the
      hypercyclic concept (Eigen and Schuster, 1979), and throw new light on the
      genetic code origin and associated problems. Also favoring this idea are data on
      complementary codon usage patterns in different genomes.

PMID- 7509482
TI  - Human leukocyte antigen subtype analysis in patients with advanced adenocarcinoma
      of the prostate.
AB  - Human leukocyte antigens (HLA) are cell surface glycoproteins that have a
      significant role in the immune system. In some cancers, changes in major
      histocompatibility complex (MHC) class I and II expression, usually a reduction
      or loss of these molecules, appear to provide a mechanism whereby tumor cells may
      escape host immunity. HLA analysis in patients with advanced adenocarcinoma of
      the prostate revealed the antigens with the highest relative risk factors as
      DRw52, DRw53, Bw73, DR2, and B5(51). As a result, determination of HLA haplotypes
      may prove to be useful in determining the men with a higher risk of developing
      prostate cancer.

PMID- 7509483
TI  - The proliferative function of basal cells in the normal and hyperplastic human
      prostate.
AB  - To obtain more insight into the proliferative function of basal and secretory
      cell types in human prostate, we studied the immunoprofile of three well
      characterized proliferation-associated antigens (Ki-67, PCNA, MIB 1) in normal
      and hyperplastic prostate tissue. Distinction between labeled basal and secretory
      cell types was made by simultaneous demonstration of the proliferation-associated
      antigens and basal cell-specific cytokeratins in identical sections. In normal
      and hyperplastic acini, approximately 70% of labeled cells were of the basal cell
      phenotype. These data clearly suggest that the proliferative compartment of the
      normal and hyperplastic epithelium is located in the basal cell layer. Compared
      to normal and hyperplastic conditions, severe proliferative abnormalities were
      detected in high-grade prostate intraepithelial neoplasias (PIN), as documented
      by the extension of the proliferative compartment up to the luminal border.
      Conversely, approximately 70% of proliferating cells detected in atypical
      hyperplasias that progressed in invasive carcinomas were localized in the
      remaining basal cell layer. These findings may indicate the proliferative role of
      basal cells in the epithelial renewal, and the development of hyperplastic and
      neoplastic disorders in the human prostate.

PMID- 7509481
TI  - Prospective, controlled study of developmental outcome in survivors of
      extracorporeal membrane oxygenation: the first 24 months.
AB  - OBJECTIVE: Survivors of venoarterial extracorporeal membrane oxygenation (ECMO)
      are considered to be at risk for developmental disabilities, but there are few
      controlled outcome studies. A prospective, controlled study of outcome was
      performed to quantify the degree and frequency of developmental disabilities in
      ECMO survivors compared with a matched control group. METHODS: From May 1987
      through November 1990, 40 of 47 neonates treated with ECMO survived at the
      University of Texas Medical Branch in Galveston. Longitudinal developmental data
      were collected, using the Bayley Scales of Infant Development, on 22 ECMO infants
      and 29 healthy term control infants at 6, 12, and 24 months. Language was
      assessed at 24 months using the Sequenced Inventory of Communication Development.
      An additional 13 ECMO infants had developmental data for at least one time point.
      RESULTS: Healthy term infants performed significantly better than ECMO infants on
      the Bayley Scales of Infant Development at 6 and 24 months and on the Sequenced
      Inventory of Communication Development at 24 months. Mean scores of ECMO infants
      were well within the average range and 77% of the ECMO infants were
      developmentally normal. CONCLUSIONS: These data suggest that early developmental
      morbidity in ECMO survivors is low, considering the severity of their neonatal
      illness.

PMID- 7509484
TI  - Immunoglobulin binding factor: a new tumor marker for prostatic tumors.
AB  - Human seminal plasma contains an immunoglobulin gamma binding factor (IgBF) with
      an estimated molecular weight of 16 kD under reducing condition. IgBF was
      detected only in the prostate, including benign prostatic hypertrophy (BPH) and
      neoplasm. The present study was performed to determine whether IgBF is a useful
      prostatic marker. Serum IgBF levels were measured in patients with prostatic
      tumors and in control patients without tumor by radioimmunoassay. Serum prostatic
      specific antigen (PSA), the standard prostatic marker, was also determined. Serum
      IgBF levels in patients with prostate cancer were significantly higher than those
      in age-matched controls (P < 0.05). Also, patients with BPH tended to have
      elevated IgBF levels than the controls, although the values were not
      statistically significant. In control patients, serum IgBF levels increased with
      advancing age. There was no correlation between serum levels of IgBF and PSA in
      patients with prostate cancer. Using cut-off level at 28.5 ng/ml (2 S.D. above
      the mean IgBF level of age-matched control), the sensitivities were 41.2% (7/17)
      for prostate cancer, 23.1% (6/26) for BPH, and 5.6% (1/18) for control patients.
      In conclusion, serum IgBF is a useful marker in the diagnosis of patients with
      prostatic tumor, and in evaluating the course of treatment.

PMID- 7509485
TI  - A more objective staging of advanced prostate cancer--routine recognition of
      malignant endocrine structures: the assessment of serum TPS, PSA, and NSE values.
AB  - Bone scans, serum tissue-specific polypeptide antigen (TPS), prostate specific
      antigen (PSA), and neuron-specific enolase (NSE) were assessed in a total of 80
      hormonally treated prostate cancer patients. Thirty-nine patients were free of
      osseous lesions; in 8 subjects, 3 or fewer scintigraphic hot spots were found; in
      29 patients, more than 3 bone lesions were recorded. In 3 patients, a partial
      contribution of endocrine cell cancer structures was found, while in one patient,
      a homogeneous small cell carcinoma was detected at autopsy. Measurement of the
      serum PSA test showed a clear-cut rise from stage D0 subjects to stage D2
      patients, with a small number of bone lesions (> or = 3). However, a relative
      decrease in the mean PSA level was measured with further progression in a number
      of hot spots in bone (> 3). Androgen threshold that is critical for the induction
      of the PSA (and PAP) expression seems to differ markedly in various cell
      subpopulations that arise during adenocarcinoma dedifferentiation. This fact
      explains not only the rise in serum PSA in the majority of progressive and
      previously castrated subjects after an initial period of hormonal responsiveness,
      but also a relative decline of androgen-dependent PSA expression with further
      tumor progression. Localized disease was accompanied with normal or just slightly
      elevated TPS concentration. In metastatic tumors, serum TPS values revealed a
      steady increase with the progression in bone. These data seem to reflect not only
      an increase in tumor proliferation rate with progressively transformed genome,
      but also the rise in the number of proliferating cells. The presence of
      nonepithelial transformed tumor structures, such as small cell cancer within a
      bulk of adenocarcinoma, reduces or normalizes numerical serotests values of both
      TPS and PSA even during tumor progression. The extent of such decline depends
      upon the bulk of the endocrine component. The assessment of the above parameters,
      especially when associated with elevated plasma NSE concentrations, may help in
      distinguishing an advanced adenocarcinoma with and without elements of malignant
      neuroendocrine structures. The proposed approach, modified by applying
      corresponding organ-specific markers, may be checked for its possible general use
      in staging protocols of various heterogeneous tumors.

PMID- 7509486
TI  - A comparison of transrectal hyperthermia, transurethral thermotherapy, urolume
      wallstent, and prostatic spiral for benign prostatic hyperplasia patients at poor
      operative risk.
AB  - Transrectal hyperthermia, transurethral thermotherapy, prostatic stent, and
      prostatic spiral were used to treat 120 poor operative risk patients with
      symptomatic benign prostatic hyperplasia. The preoperative subjective and
      objective conditions of the four groups (each of 30 patients) were comparable.
      None of the patients had an indwelling catheter, but according to flow nomograms,
      all were obstructed. The greatest increase in peak flow rate was observed after
      stent placement, while the greatest decrease of residual urine volume was seen
      after the insertion of the stent and transrectal hyperthermia. According to
      maximum flow nomograms, only the placement of the stent resolved bladder outlet
      obstruction. The greatest improvement in subjective symptoms was the result of
      stent insertion, but the heating procedures also caused a significant reduction
      of symptom scores. The spiral produced satisfactory results only in the short
      term.

PMID- 7509487
TI  - Antibodies to GPIIb alpha (300-312) inhibit Fg binding, clot retraction, and
      platelet adhesion to multiple ligands.
AB  - We previously reported that a peptide with the sequence Gly-Ala-Pro-Leu (GAPL)
      found as residues 309-312 in glycoprotein IIb alpha (GPIIb) comprises at least
      part of a Fg binding site on GPIIb (1). Subsequent studies demonstrated that a
      peptide corresponding to residues 300-312 of GPIIb alpha can bind to Fg and Vn,
      and is a potent inhibitor of platelet aggregation and the adhesion of activated
      platelets to at least four adhesive ligands: Fg, Fn, Vn, and vWf (2). Here, the
      production and initial characterization of polyclonal antibodies against this
      peptide are described. ELISAs and dot-blot assays reveal the specificity of the
      antibodies for the peptide immunogen. In immunoblots, the antibodies recognize
      GPIIb under reducing conditions. The binding of Fg to immobilized GPIIb/IIIa, the
      rate of clot retraction and the adhesion of stimulated platelets to Fg,
      fibronectin (Fn), vitronectin (Vn), and von Willebrand factor (vWf) were
      inhibited by these antibodies, but not by a control IgG. These results together
      with our earlier published data indicate that GPIIb alpha (300-312) comprises at
      least part of a common ligand binding site within the integrin alpha IIb subunit.

PMID- 7509488
TI  - Hyaluronan-binding protein in chondrogenesis and angiogenesis in the developing
      limb.

PMID- 7509489
TI  - Tenascin variants: ligands and expression.

PMID- 7509490
TI  - Roles of adhesion molecules NCAM and tenascin in limb skeletogenesis: analysis
      with antibody perturbation, exogenous gene expression, talpid mutants and activin
      stimulation.

PMID- 7509491
TI  - Agonist-induced hydrolysis of inositol phospholipids in newt forelimb
      regeneration blastemas.

PMID- 7509492
TI  - GABA and glycine in retinal amacrine cells: combined Golgi impregnation and
      immunocytochemistry.
AB  - Golgi-impregnated amacrine cells in the all-cone lizard retina (Anolis
      carolinensis) were characterized on the bases of dendritic and somatic criteria.
      Four major cell categories, comprising 23 types were identified: three non
      stratified, 13 monostratified, five bistratified, and two tristratified types.
      Four of the cell types comprised two to four subtypes based on stratification of
      their dendrites within the inner plexiform layer (IPL). Golgi impregnation
      strongly favoured monostratified amacrine cells with cell bodies at the proximal
      margin of the inner nuclear layer. The neurotransmitter content of each of the 23
      amacrine cell types was examined by combined Golgi-immunocytochemistry after
      morphological classification. Putative neurotransmitters examined included gamma
      aminobutyric acid (GABA), glycine (GLY) and aspartate (ASP). Seventeen cell types
      showed GABA-immunoreactivity (IR), three cell types showed GLY-IR, and four cell
      types showed neither GABA-IR nor GLY-IR. No cell types showed ASP-IR. Each cell
      type had a characteristic neurochemical signature, with the exception of one
      monostratified cell type that showed three different neurochemical signatures.
      Postembedding immunocytochemistry on conventionally processed retinas confirmed
      the localization of glutamic acid decarboxylase, the synthetic enzyme for GABA,
      to cells similar to several of the GABA-IR Golgi-stained types. Postembedding
      immunocytochemistry for tyrosine hydroxylase (the synthetic enzyme for
      catecholamines) and GABA on serial sections demonstrated colocalization of GABA
      and a catecholamine, probably dopamine, in a bistratified amacrine cell type. We
      conclude that GABA-IR amacrine cell types are more numerous and morphologically
      heterogeneous than GLY-IR amacrine cells. The morphological heterogeneity and,
      with one exception, exclusivity of GABA-IR and GLY-IR amacrine cell types
      indicate that both neurotransmitters play a variety and different functional
      roles in the lizard inner retina.

PMID- 7509493
TI  - A new skin equivalent: keratinocytes proliferated and differentiated on collagen
      sponge containing fibroblasts.
AB  - Three types of artificial skin containing keratinocytic components were prepared
      and tested for comparison. Keratinocytes were cultured on the artificial skin
      dermis (collagen sponge) by the air-liquid interface culture method. In order to
      create continuous keratinocytic layers on the artificial skin dermis, pores of
      its uppermost layer were filled beforehand with type I collagen gel, Matrigel, or
      fibroblasts. A band of keratinocytes consisting of two to six cell layers was
      formed on collagen gel-coated artificial skin dermis. On Matrigel-coated
      artificial skin dermis, keratinocytes were piled up into about 20 cell layers,
      but cell differentiation was incomplete; cornified material was not fully
      developed, and the proportion of cuboidal cells was very high compared with
      normal epidermis. Keratinocytes formed continuous layers on the fibroblasts
      artificial skin dermis complex without gel coating. Keratinocytes proliferated
      well and differentiated properly on this matrix, and their histologic appearance
      was similar to that of normal epidermis. Thus keratinocytes cultured on the
      fibroblast-artificial skin dermis complex seem to be a good skin equivalent.

PMID- 7509494
TI  - Emergency department screening for ectopic pregnancy: a prospective US study.
AB  - PURPOSE: To determine the effectiveness of pelvic sonography as a screening test
      for ectopic pregnancy. MATERIALS AND METHODS: Pelvic sonograms were prospectively
      analyzed in 1,427 consecutive patients with a serum level of the beta subunit of
      human chorionic gonadotropin of over 1,500 IU/L. RESULTS: Sonograms were
      diagnostic in 1,158 patients and indeterminate in 269. When indeterminate studies
      were considered falsely negative, the diagnostic accuracy was 81%. Twenty-four
      percent of patients with indeterminate studies were subsequently proved to have
      ectopic pregnancy. In ectopic pregnancy (n = 103), the most common finding was a
      complex adnexal mass (specificity = 92% [P < .001]). The sensitivity and
      specificity of screening sonography for ectopic pregnancy were 99% and 84%,
      respectively. CONCLUSION: Pelvic sonography is an effective screening test for
      ectopic pregnancy. Having a one in four chance of harboring an ectopic pregnancy,
      patients with indeterminate studies require close follow-up. The presence of a
      complex adnexal mass is a strong predictor of ectopic pregnancy.

PMID- 7509496
TI  - Effects of chronic mianserin administration on serotonin metabolism and receptors
      in the 5-hydroxytryptophan depression model.
AB  - 1. To further investigate a previous postulate that increased serotonergic
      activity may cause depression, the effects of chronic mianserin administration on
      5-HT, its metabolites, and the subtypes of 5-HT receptors were studied. 2. The
      levels of 5-HT, 5-hydroxyindoleacetic acid, 5-HTP, 5-HT turnover and their
      response to 5-HTP administration all exhibited no change following mianserin
      treatment. 3. The Bmax value of the high affinity site of the 5-HT-1A receptor
      increased and the Bmax value of 5-HT-2 receptor decreased with no change in the
      low affinity site of the 5-HT-1A receptor nor in the 5-HT-1B receptor. 4. The
      response to 5-HTP administration showed no change in any of these receptors. 5.
      These results suggest that the chronic mianserin administration might block both
      the 5-HT-2 and 5-HT-1A receptors in the 5-hydroxytryptophan depression model.

PMID- 7509495
TI  - Risperidone versus clozapine in the treatment of schizophrenic patients with
      acute symptoms: a double blind, randomized trial.
AB  - 1. In order to verify the hypothesis that risperidone is a useful therapeutic
      alternative to clozapine the authors carried out a randomized double blind trial
      in 59 patients with paranoid hallucinatory psychoses. 2. In a treatment lasting
      28 days three groups of patients received either 4 mg risperidone (N = 20), 8 mg
      risperidone (N = 19), or 400 mg clozapine (N = 20) daily. 3. The tolerance of 4
      mg risperidone was globally assessed as being better than that of 400 mg
      clozapine. Drop-outs under clozapine were mostly caused by side effects, whereas
      under risperidone they tended to occur for therapeutic inefficacy. 4. The
      antipsychotic effect was highly significant and clinically relevant under both
      risperidone and clozapine.

PMID- 7509497
TI  - Repeated electroconvulsive stimuli: changes in neuropeptide Y, neurotensin and
      tachykinin concentrations in time.
AB  - 1. The effects of repeated electroconvulsive stimuli (ECS) on neuropeptide Y
      (NPY)-, neurokinin A (NKA)-, substance P (SP)- and neurotensin (NT)- like
      immunoreactivity (-LI) levels in specific rat brain regions were studied in order
      to establish changes in peptide tissue concentrations in time after the last ECS.
      2. The rats were sacrificed 15 minutes, 60 minutes, 1 day, 7 days or 15 days
      after the sixth sham ECS or ECS, using focused microwave irradiation. 3.
      Following dissection of the brains, peptides were extracted and measured in
      extract aliquots by radioimmunoassays. 4. ECS increased NPY-LI in both right and
      left hippocampus, frontal cortex and occipital cortex at 15 min, 60 min and 1 day
      after the treatments. Seven days following the last treatment, NPY-LI
      concentrations were elevated in the left hippocampus and occipital cortex but not
      in the corresponding right structures. Fifteen days following the last ECS
      treatment no changes in NPY concentrations were seen. 5. Also NKA-LI was
      increased in both the right and left hippocampus; the duration of changes was
      identical to those of NPY-LI. 6. No effects on SP- or NT-LI were found. 7. These
      results are in line with our hypothesis that one of the ECT's mechanisms of
      action might involve its effects on NPY and NKA.

PMID- 7509498
TI  - Effects of luminal vasopressin on intracellular calcium in microperfused rat
      medullary thick ascending limb.
AB  - Recent evidence suggests that vasopressin exerts a regulatory influence on
      transport processes in the rabbit cortical collecting duct via both the
      basolateral and luminal membranes. The present study was undertaken to examine
      whether luminal vasopressin receptors, coupled to changes in intracellular
      calcium, were also present in microperfused rat medullary thick ascending limb
      (mTAL), a key element of the urine concentrating mechanism. Addition of 1 nM
      vasopressin to the luminal microperfusate elicited a small but significant and
      sustained rise in intracellular calcium, from basal values of 100.1 +/- 20.1 to
      169.6 +/- 24.1 nM after 250 s. The effect observed following luminal addition of
      vasopressin was dose-dependent, with a larger increment of 190.2 +/- 32.2 nM
      evoked by addition of 1 microM vasopressin. Addition of 1 nM oxytocin to the
      lumen did not cause a significant increase in intracellular calcium
      concentration, consistent with the response to vasopressin being mediated by
      specific luminal vasopressin receptors. In the absence of calcium in the bath and
      lumen together or in the bath alone, a residual response to 1 microM luminal
      vasopressin was still evident, suggestive of a small component of release of
      calcium from intracellular stores. Selective calcium removal from the luminal
      microperfusate alone left the response intact. These data are congruous with a
      model of vasopressin-induced entry of calcium which occurs via the basolateral
      membrane following ligand binding to the apical membrane. These findings, coupled
      with earlier observations in the collecting duct, suggest that a fundamental re
      assessment of where and how vasopressin, and perhaps other hormones, acts in the
      kidney may be required.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509499
TI  - Diminished diuretic and natriuretic response to furosemide in potassium-depleted
      rats.
AB  - Renal clearance and tubule microperfusion experiments were carried out to
      investigate the effects of chronic potassium depletion upon the renal response to
      furosemide. Rats kept on a potassium-deficient diet for 3 weeks developed
      hypokalemia, metabolic alkalosis, and decreased aldosterone levels. These rats
      responded to an oral administration of furosemide (32 mg/kg) with a blunted
      excretion rate of urine and sodium. Whereas furosemide increased fractional urine
      sodium excretion to 5.2% in control rats, the corresponding rate in potassium
      depleted rats was 2.8%. The urinary excretion of furosemide was also
      significantly reduced during potassium depletion from 3.06 mg/kg in control rats
      to 0.97 mg/kg in potassium-depleted rats. In separate experiments, loops of Henle
      were pump-perfused with furosemide-containing solutions in control and potassium
      depleted rats. No major modification of the inhibitory effects of furosemide on
      sodium transport was observed when the potassium concentration of the perfusion
      fluid was kept at the low levels expected in hypokalemic rats. Metabolic
      alkalosis unaccompanied by potassium deprivation did not decrease the diuretic
      response to furosemide. These experiments indicate that potassium deprivation
      reduces the diuretic effects of furosemide by mechanisms including diminished
      furosemide delivery to its tubule site of action.

PMID- 7509501
TI  - Characteristics of the luminal proton pump in malpighian tubules of the ant.
AB  - The active pump mechanisms involved in K+ secretion of the malpighian tubules of
      the ant and present in the luminal membrane were investigated on isolated,
      luminally perfused tubules of Formica. The specific blocker for vacuolar type
      ATPases, bafilomycin A1, was found to half-maximally inhibit secretion at a
      concentration of 10(-5) mol/l when added to the lumen. N-Ethylmaleimide reduced
      the calculated short circuit current (Isc) to 78 and 21% of control value when
      added at 5 x 10(-4) mol/l, respectively, to the lumen and the bath. Reducing
      luminal pH inhibited Isc with a half-maximal inhibition at a luminal pH of 4.5.
      Acidified omeprazole, Schering compound 28080 and vanadate (both 10(-3) and 10(
      4) mol/l) inhibited Isc only partially. The present data suggest that the luminal
      membrane of ant malpighian tubules contains a H+ pump. This pump is only poorly
      bafilomycin-sensitive. Furthermore, additional active transport systems
      responsible for secretion may be present. Part of these results have been
      published as abstracts.

PMID- 7509502
TI  - The role of the proximal tubule in ochratoxin A nephrotoxicity in vivo:
      toxodynamic and toxokinetic aspects.
AB  - The proximal tubule of the kidney is regarded the main intrarenal target of the
      nephrotoxin Ochratoxin A (OTA). To gain further insight into the importance of
      the proximal tubule we investigated renal p-aminohippurate (PAH), inorganic
      phosphate (P), amino acid (AA) and OTA handling in male Wistar rats. The acute
      application of OTA (1.2 mg/kg) did not affect the renal handling of any of the
      substances investigated in contrast to the acute effect of OTA on 'postproximal'
      parts of the nephron. Application of OTA (0.5 mg/(kg.day)) over 6 days resulted
      in a dramatic decrease of the transport maximum of PAH (reduction to 15% of
      control) and to an increase of the apparent affinity of PAH to the organic anion
      transporter. Absolute excretion of P was not increased, whereas--due to the
      reduced GFR--the fractional excretion (FE) increased (to 180% of control). FE of
      the AA was not affected by OTA. Free-flow micropuncture experiments performed in
      L-homoarginine-loaded rats--to unmask possible small alterations of the amino
      acid transport kinetics--revealed that the proximal tubular transport of amino
      acids is not impaired by OTA. Subchronic exposure of the animals to OTA reduced
      the excretion of the mycotoxin itself to about 15% of controls. We conclude that
      the proximal tubule is not the main but one important intrarenal target of
      subchronically applied OTA. Furthermore, the action of OTA on the proximal tubule
      leads to decreased capacity to eliminate OTA possibly resulting in a self
      enhancing effect.

PMID- 7509500
TI  - Effect of low and high potassium diets on H(+)-K(+)-ATPase and Na(+)-K(+)-ATPase
      activities in the rat inner medullary collecting duct cells.
AB  - This study was designed to measure H-K-ATPase and Na-K-ATPase activities in rat
      inner medullary collecting duct (IMCD) cells during potassium depletion and
      loading. Both enzyme activities were similarly distributed from the proximal to
      the distal portion of this nephron segment. One week K depletion did not
      stimulate H-K-ATPase activity but reduced Na-K-ATPase activity. Within 2 weeks
      after the onset of potassium depletion, the rats developed metabolic alkalosis,
      and H-K-ATPase activity was suppressed while Na-K-ATPase activity had returned to
      control values. H-K-ATPase activity was suppressed following potassium loading
      whereas Na-K-ATPase activity was unchanged. The results are consistent with the
      presence of H-K-ATPase in IMCD and indicate that H-K-ATPase and Na-K-ATPase
      activities are modulated by potassium intake.

PMID- 7509503
TI  - Protective effect of antiinflammatory corticosteroid triamcinolone in cisplatin
      nephrotoxicity.
AB  - The corticosteroid, triamcinolone, was examined as a potential antagonist for the
      nephrotoxicity of cisplatin in female Wistar rats. The changes in renal function
      and renal morphology were assessed on the 3rd day after administration of
      cisplatin (7.5 mg/kg BW) and in animals given triamcinolone retard (4 mg/kg BW) 6
      h before administration of cisplatin. Pretreatment with triamcinolone resulted in
      much less severe changes in renal function after cisplatin administration (serum
      urea: triamcinolone plus cisplatin 14.29 +/- 1.90 mg/l, cisplatin alone 21.60 +/-
      2.34 mg/l, p < 0.05, control 2.78 +/- 0.19 mg/l, serum creatinine: triamcinolone
      plus cisplatin 0.21 +/- 0.02 mg/l, cisplatin alone 0.30 +/- 0.02 mg/l, p < 0.05,
      control 0.06 +/- 0.01 mg/l). In contrast to cisplatin-treated animals in
      triamcinolone-pretreated rats alterations of water content were found neither in
      renal cortex (triamcinolone plus cisplatin 3.39 +/- 0.16 g/g dry weight,
      cisplatin alone 4.07 +/- 0.07 g/g dry weight, control 3.07 +/- 0.07 g/g dry
      weight) nor in outer medulla (triamcinolone plus cisplatin 4.20 +/- 0.22 g/g dry
      weight, cisplatin alone 4.98 +/- 0.21 g/g dry weight, control 3.84 +/- 0.11 g/g
      dry weight) compared to control. The structure of the kidney following cisplatin
      administration demonstrated extensive lesions of S3 segments of the proximal
      tubule. The changes in proximal convoluted tubules were widespread and ranged
      from the decrease of the amount of microvilli to loss of brush border or even to
      cell death. In triamcinolone-pretreated rats the structure of the cortex appeared
      to be virtually normal and tissue of medulla was only slightly damaged.

PMID- 7509505
TI  - Staging of prostate cancer.
AB  - The clinical and pathologic staging of prostate cancer involves determination of
      the anatomic extent and burden of tumor based on the best available data. Two
      major classification schemes are currently used: the modified American system and
      the TNM system [primary tumor (T), regional lymph node (N), and metastases (M)].
      Both systems stratify patients according to the method of tumor detection,
      separating nonpalpable "incidental" prostate cancers detected during
      transurethral resection for clinically benign prostatic hyperplasia (BPH) and
      palpable cancers detected by digital rectal examination. These staging systems
      also recognize nonpalpable tumors detected by an elevated serum prostate-specific
      antigen (PSA) level or an abnormal transrectal ultrasound image. Current staging
      is limited by a significant level of clinical understaging (up to 59%, in our
      experience) and overstaging (up to 5%) according to comparison with pathologic
      examination of resected specimens. Proposed improvements in staging include
      preoperative systematic sextant biopsies to assess tumor volume, volume-based
      prognostic index, and a multiple prognostic index. In this report, we evaluate
      the current aspects of clinical and pathologic staging of prostate cancer with
      emphasis on the early stages in which there is the greatest chance of cure.

PMID- 7509504
TI  - Clinicopathologic correlation of laser lesion expansion after treatment of
      choroidal neovascularization.
AB  - The clinicopathologic features of photocoagulation lesion expansion after two
      separate sessions of krypton red laser for choroidal neovascularization (CNV) in
      an eye with age-related macular degeneration are presented. The area of expansion
      is characterized by retinal pigment epithelial atrophy and loss of the
      photoreceptor cell layer. A thin margin of retinal pigment epithelium
      hypopigmentation and variable photoreceptor cell layer degeneration also borders
      the lesion in some areas.

PMID- 7509506
TI  - Antibodies against non-structural c100/3 and structural core antigen of hepatitis
      C virus (HCV) in hemodialysis patients.
AB  - Two groups of patients undergoing hemodialysis (HD) maintenance were evaluated
      for their antibody response to non-structural c100/3 protein and structural core
      protein of hepatitis C virus (HCV). Forty-six patients (Group 1) never presented
      liver abnormalities during HD treatment, while 52 patients (Group 2) had either
      current or prior liver enzyme elevations. Prevalence rates of 32.6% and 41.3%
      were found for anti-c100/3 and anti-HCV core antibodies, respectively, in
      patients with silent infections (Group 1). The rate of anti-c100/3 in patients of
      Group 2 was 71.15% and reached 86.5% for anti-HCV core antibodies. The
      recognition of anti-c100/3 and anti-core antibodies was significantly higher in
      Group 2 than in Group 1. A line immunoassay composed of structural and non
      structural peptides was used as a confirmation assay. HBV infection, measured by
      the presence of anti-HBc antibodies, was observed in 39.8% of the patients. Six
      were HBsAg chronic carriers and 13 had naturally acquired anti-HBs antibodies.
      The duration of HD treatment was correlated with anti-HCV positivity. A high
      prevalence of 96.7% (Group 2) was found in patients who underwent more than 5
      years of treatment. Our results suggest that anti-HCV core ELISA is more accurate
      for detecting HCV infection than anti-c100/3. Although the risk associated with
      the duration of HD treatment and blood transfusion was high, additional factors
      such as a significant non-transfusional spread of HCV seems to play a role as
      well. The identification of infective patients by more sensitive methods for HCV
      genome detection should help to control the transmission of HCV in the unit under
      study.

PMID- 7509507
TI  - Elevated prostate-specific antigen level and the negative prostate biopsy.

PMID- 7509508
TI  - Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with
      orgaran (Org 10172)
AB  - Heparin-induced thrombocytopenia (HIT) with thrombosis occurs in about 1 in 2,000
      heparin-treated patients. The arterial or venous thromboses may threaten life and
      limb hence alternative anticoagulation is needed. Some alternative treatments are
      possible i.e. LMWH, Ancrod, prostacyclin analogues, Dextran, aspirin and oral
      anticoagulants, but each has its drawbacks. This report reviews treatment of HIT
      patients with Orgaran (Org 10172), a low molecular weight heparinoid. Because of
      its proven antithrombotic activity Orgaran was used to treat 230 HIT patients.
      One hundred and fifty, nine patients presented with at least one thrombotic
      problem, which in 88 was due to the heparin use. 92.8% of the patients were
      considered to have adequately responded to Orgaran during the treatment period.
      Fifty-nine deaths (25.7%) occurred of which 7 (3.0%) were attributed to Orgaran
      use. The remaining 52 deaths, 27 of which occurred after Orgaran treatment was
      successfully terminated, were due to the severe underlying disorders in these
      patients. These results and the lower cross-reactivity rate (approximately 10%)
      with the heparin-induced antibody compared with that of the LMWH (> 90%) suggest
      that although problems remain, Orgaran can be a valuable alternative treatment
      for patients who suffer from HIT and who require anticoagulation.

PMID- 7509510
TI  - Detection of antiphospholipid antibodies by flow cytometry: rapid detection of
      antibody isotype and phospholipid specificity.
AB  - Laboratory diagnosis of antiphospholipid antibodies is important in patients with
      clinical features of the antiphospholipid syndrome, such as thrombosis and fetal
      loss. We have developed a novel method for the detection of antiphospholipid
      antibodies using flow cytometry. Anionic phospholipids cardiolipin,
      phosphatidylserine and phosphatidylinositol are coated onto polystyrene beads of
      different sizes, allowing detection and semiquantitation of their respective
      phospholipid antibody isotypes. The results of the flow cytometric method closely
      correlate those of the standardised anticardiolipin enzyme-linked immunosorbent
      assay (ELISA), but the method is quicker and is versatile in its ability to
      detect IgG, IgM and IgA antibody isotypes at the same time. The method promises
      to be useful in evaluating the significance of phospholipid specificity and
      antibody isotypes in patients with the antiphospholipid syndrome.

PMID- 7509509
TI  - Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective
      surgery for malignant disease? A double-blind, randomised, multicentre
      comparison. ANZ-Organon Investigators' Group.
AB  - This double-blind, randomised, multicentre trial in 513 patients having elective
      surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and
      safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of
      Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc)
      twice-daily with that of twice-daily injections of 5,000 units standard heparin.
      The main study endpoints were the development of postoperative VT detected by
      125I-fibrinogen leg scanning, and the onset of clinically significant venous
      thromboembolism or bleeding. "Intent to treat" analysis showed a statistically
      non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than
      after heparin (14.9%) and there was no difference in bleeding complications
      between the two study groups. Results remained similar if only patients who
      completed the intended course of therapy ("compliant patients") were analysed.
      Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We
      now show it is also safe and effective in patients having major surgery for
      cancer.

PMID- 7509511
TI  - Continuous registration of thrombin generation in plasma, its use for the
      determination of the thrombin potential.
AB  - A method is described by which the time-course of thrombin generation in plasma
      can be obtained from a continuous optical density recording of p-nitroaniline
      (pNA) production in a 2:3 diluted plasma. A chromogenic substrate, methylmalonyl
      methylanalyl-arginyl-pNA (SQ 68), is used that is specifically split by thrombin
      but at a low rate. The thrombin that appears and disappears in the plasma does
      not split more than 5% of the substrate added, so the rate of substrate
      conversion is in good approximation proportional to the amidolytic activity in
      the plasma over the entire period of thrombin generation. The course of the
      enzyme concentration can be calculated from the amidolytic activity curve. It is
      shown that the thrombin generation curves obtained in this way are essentially
      identical to those obtained via the classical subsampling method. The presence of
      SQ 68 influences the amount of free thrombin that appears in plasma because it
      competitively inhibits the inactivation of thrombin by AT III and alpha 2
      macroglobulin. The inhibition of the thrombin peak by heparin, relative to an
      uninhibited control, remains unaltered by the presence of the substrate. From the
      course of thrombin activity and the prevailing decay constants, the course of
      prothrombin conversion velocity can be calculated. Prothrombin conversion was
      seen to be inhibited at high (> 500 microM) substrate concentrations only, and
      experimental conditions are found under which the inhibition of the clotting
      process by the substrate is negligible. The amidolytic activity is the sum of the
      activities of free thrombin and of the alpha 2 macroglobulin-thrombin complex
      formed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509512
TI  - Inhibition of endothelial cell expression of plasminogen activator inhibitor type
      1 by gemfibrozil.
AB  - Increased concentrations of plasminogen activator inhibitor type-1 (PAI-1) in
      plasma are associated with impaired fibrinolysis and venous and arterial thrombo
      embolic disease. In pilot studies designed to identify pharmacologic approaches
      capable of diminishing such increases, we found that gemfibrozil attenuated the
      stimulation of synthesis of PAI-1 in a human, immortal, hepatoma cell line (Hep
      G2) induced by platelets. The present study was performed to determine whether it
      exerts analogous effects in non-immortal endothelial cells and whether it may
      therefore facilitate fibrinolysis locally in vivo. Human umbilical vein
      endothelial cells were incubated with pharmacologic concentrations of
      gemfibrozil. Gemfibrozil, 100 microM, suppressed basal PAI-1 production by 15%
      and attenuated the augmentation of synthesis of PAI-1 induced by lysates from
      platelets (4 x 10(7)/ml) by 36% over 24 h without inhibiting overall protein
      synthesis. In addition, the increases in PAI-1 mRNA otherwise induced by platelet
      lysates over 6 h were suppressed by 49% (Northern blots) without any demonstrable
      change in the intracellular half-life of PAI-1 mRNA. Pulse-chase experiments
      demonstrated diminution of PAI-1 protein synthesis in parallel with the changes
      observed in PAI-1 mRNA. To determine whether these effects of gemfibrozil on
      endothelial cells in vitro were paralleled by consistent changes in the
      concentrations of PAI-1 in plasma in vivo, we studied rabbits with induced
      carotid artery thrombosis and thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509513
TI  - Correlation between platelet aggregation and dephosphorylation of a 68 kDa
      protein revealed through the use of putative PKC inhibitors.
AB  - The efficacy of two structurally and functionally unrelated protein kinase C
      (PKC) inhibitors, chelerythrine and calphostin C, was assessed in intact human
      platelets by studying platelet aggregation in response to stimulation with
      phorbol 12-myristate 13-acetate (PMA) or the thromboxane-A2 mimetic, U46619.
      Surprisingly, both inhibitors increased aggregation in response to PMA, but
      decreased aggregation in response to U46619. To further explore this phenomenon,
      gel electrophoresis of 32P-labelled proteins from PMA- or U46619-stimulated
      platelets in the presence and absence of the two putative PKC inhibitors was
      performed. Although neither chelerythrine nor calphostin C proved to be effective
      PKC inhibitors in intact human platelets, a strong correlation between the
      dephosphorylation of a 68 kDa protein and the rate of platelet aggregation was
      observed. From these results, the indiscriminate use of PKC inhibitors in whole
      platelets is questioned and attention is drawn to the role of protein
      dephosphorylation in platelet activation. The 68 kDa protein was the major
      phosphorylated substrate in resting platelets. Okadaic acid increased
      phosphorylation of this band, indicating active phosphate group turnover under
      resting conditions.

PMID- 7509514
TI  - Enhancement of FK506 nephrotoxicity by sodium depletion in an experimental rat
      model.
AB  - FK506 can show efficacy in transplant rejection even after other
      immunosuppressive drugs have been ineffective. However, the lack of a suitable
      animal model has hindered the study of FK nephrotoxicity, which has been noted as
      a common adverse effect in human trials. In this paper, we report a model of
      chronic FK nephrotoxicity in which renal structure and function are worsened by
      sodium depletion. Pair-fed male Sprague-Dawley rats were given FK (6 mg/kg p.o.)
      or vehicle for 21 days on a low-salt or normal diet. There was no significant
      difference in body weight between FK and vehicle groups. The FK whole-blood
      trough levels (3-10 ng/ml) in rats are similar to those in FK treated transplant
      patients. In sodium-depleted rats, FK clearly decreased GFR (0.09 +/- 0.03
      ml/min/100 g vs. 0.94 +/- 0.06 ml/min/100 g in the vehicle group, P < 0.01),
      urinary osmolarity (UOsm, P < 0.01) and plasma magnesium (P < 0.01) and increased
      plasma creatinine (Pcr, P < 0.01), fractional excretion of magnesium (P < 0.01),
      urine volume (P < 0.01), plasma renin activity (PRA, P < 0.05), and alanine
      aminopeptidase (AAP, P < 0.05) as compared with those in the vehicle group. Salt
      depletion significantly potentiated these functional changes as compared with
      those in the normal salt group (GFR, UOsm, Pcr, PRA, and AAP of the low salt
      group vs. those of the normal salt group, P < 0.05 by ANOVA). In the sodium
      depleted rats, the main lesion in the rat kidneys was focal collapse and
      vacuolization in proximal tubules, but there was also significant interstitial
      fibrosis. In contrast, no injury was observed in the sodium-replete rat kidneys.
      In conclusion, an experimental model of FK nephrotoxicity in sodium-depleted rats
      has been developed that is characterized by reduced GFR and structural damage to
      the proximal tubule accompanied by interstitial fibrosis. Sodium depletion
      appears to potentiate these changes at blood levels similar to those achieved in
      patients receiving FK.

PMID- 7509515
TI  - The evaluation of candidates for renal transplantation. The current practice of
      U.S. transplant centers.
AB  - The criteria for acceptance of candidates for renal transplantation varies
      throughout the United States. The Patient Care and Education Committee of the
      American Society of Transplant Physicians conducted a survey of all U.S. centers
      that participate in the United Network for Organ Sharing (UNOS) concerning their
      evaluation of adult candidates for kidney transplantation. The response to each
      question was examined according to the specialty of the individual who filled out
      the questionnaire, as well as the type of transplant center (university or
      private) and the size of the center. The response rate to the survey was 81%
      (147/182). We found the following: (1) university-based and larger centers
      accepted more medically complicated patients; (2) 83% noted that attendance to
      dialysis was an important indicator of compliance after transplantation; (3) 79%
      did not require preoperative blood transfusions for cadaver kidney recipients;
      (4) 66% set no specific upper age limit for transplantation; (5) 56% excluded
      patients with chronic active hepatitis in the setting of hepatitis B antigenemia;
      (6) 50% had no specific policy for evaluating hepatitis C antibody-positive
      patients, while 54% excluded the use of hepatitis C antibody-positive donors, and
      (7) 15% obtained coronary angiography on all diabetic patients. U.S. transplant
      centers have a heterogeneous approach to the evaluation of patients for renal
      transplantation, particularly in the areas of viral hepatitis, cardiovascular
      disease, and noncompliance. University-based centers and centers that perform a
      larger number of transplants accept more medically complicated patients.

PMID- 7509517
TI  - Huxley versus Owen: the hippocampus minor and evolution.
AB  - In Victorian Britain a major debate over evolution raged between Thomas H. Huxley
      and Richard Owen. The central issue between them was whether or not the human
      brain was unique in having a hippocampus minor (also known as the calcar avis), a
      posterior horn and a posterior lobe.

PMID- 7509516
TI  - FK506 trough levels in whole blood and plasma in liver transplant recipients.
      Correlation with clinical events and side effects.
AB  - FK506 trough levels were measured by ELISA in paired whole-blood and plasma
      samples in 59 liver transplant recipients. Patients with nephrotoxicity had
      higher FK506 whole-blood and plasma levels (27.5 +/- 3.2 ng/ml and 1.44 +/- 0.14
      ng/ml) than patients with stable liver function (15.2 +/- 2.1 ng/ml and 0.98 +/-
      0.15 ng/ml, P < 0.05 and P < 0.01, respectively). Patients with acute rejection
      had FK506 whole-blood and plasma levels within the same range as patients with
      stable liver function. Patients with severe neurotoxicity had significantly
      higher FK506 whole-blood and plasma levels (31.3 +/- 6.8 ng/ml and 3.9 +/- 1.4
      ng/ml) in comparison with patients with mild-to-moderate neurotoxicity (18.1 +/-
      2.4 ng/ml and 1.1 +/- 0.13 ng/ml) (P = 0.048 and P < 0.001, respectively). Long
      term use of FK506 was associated with a significant reduction in glomerular
      filtration rate at 1-year posttransplant in patients on primary FK506 treatment
      (33%, P < 0.001). The reduction in glomerular filtration rate correlated with the
      yearly mean FK506 plasma but not with whole-blood levels or FK506 dose. There was
      a correlation between FK506 whole-blood and plasma levels (r = 0.713, P < 0.001)
      but not between the levels (whole blood or plasma) and FK506 dose (mg/day or
      mg/kg/day). The mean FK506 whole-blood and plasma levels were 14.1 +/- 0.26 ng/ml
      and 0.96 +/- 0.75 ng/ml, respectively. There was a large intra- and interpatient
      variability in the ratio between whole-blood and plasma levels (range 1.0-73.5),
      with a mean ratio of 18.0 +/- 0.28 (+/- SEM). In conclusion, monitoring of FK506
      trough levels is of importance to avoid nephro- and neurotoxicity, but monitoring
      is only of limited help to avoid acute rejection. Monitoring of FK506 levels in
      plasma seems to be superior to that in whole blood.

PMID- 7509518
TI  - Receptor-independent activation of mast cells by bradykinin and related peptides.

PMID- 7509519
TI  - Structure and function of voltage-gated ion channels.
AB  - The principal subunits of the voltage-gated Na+, Ca2+ and K+ channels are members
      of a related gene family and are functionally autonomous in voltage-dependent
      activation, ion conductance and inactivation. In this article, recent work
      locating the structural elements that are responsible for these three basic
      functions of the voltage-gated ion channels is reviewed. These studies reveal
      strong functional analogies among the different ion channels and suggest that the
      striking differences in their properties arise as variations on a common
      structural and functional theme.

PMID- 7509520
TI  - Molecular biology of opioid receptors.
AB  - Opium and its derivatives are potent analgesics that also have many other
      pharmacological effects in the nervous system. These agents and the endogenous
      opioid peptides exert their effects by interacting with high-affinity receptors.
      Complementary DNAs encoding the delta, kappa and mu opioid receptors have been
      isolated and characterized. These receptors, which are members of the superfamily
      of seven-transmembrane spanning receptors, share a high degree of amino acid
      sequence similarity with approximately 50% of the residues being identical. The
      cloned opioid receptors mediate agonist inhibition of cyclic AMP formation and
      have pharmacological properties similar to the endogenous proteins. The cloning
      of these receptors will facilitate the development of new clinically useful
      compounds as well as studies of the molecular basis of tolerance and drug
      addiction.

PMID- 7509521
TI  - Identification and cell lineage of individual neural precursors in the Drosophila
      CNS.
AB  - The Drosophila CNS is complex enough to serve as a model for many of the
      molecular, cellular and developmental functions of the vertebrate CNS, yet simple
      enough for single-cell analysis. Recent advances have provided molecular markers
      that allow most Drosophila CNS precursors to be uniquely identified, as well as
      methods for determining the complete cell lineage of each precursor. A detailed
      understanding of wild-type neurogenesis, combined with existing molecular genetic
      techniques, should provide insight into the fundamental mechanisms that generate
      neuronal and glial diversity.

PMID- 7509522
TI  - The distribution of myelin basic protein mRNAs within myelinating
      oligodendrocytes.
AB  - The nervous system contains oligodendrocytes with processes that are greatly
      extended in space. It is now clear that there are numerous complex, poorly
      understood mechanisms by which polypeptides are synthesized and delivered to
      their sites of function in these cells. One mechanism is by the active
      positioning of mRNAs encoding certain proteins to restricted intracellular
      subdomains. Perhaps the best studied example of this in the vertebrate CNS is the
      translocation of myelin basic protein mRNAs to the forming myelin sheath, where
      the newly synthesized polypeptides, which avidly associate with membranes, can be
      directly incorporated into the myelin membrane. Evidence for this conclusion is
      presented here in the context of related work on the general phenomenon of mRNA
      translocation that is under analysis in other systems.

PMID- 7509523
TI  - NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms.
AB  - Long-term potentiation in the CA1 region of the hippocampus is the most
      extensively studied model of activity-dependent synaptic plasticity in the
      mammalian brain. Its induction normally involves activation of postsynaptic N
      methyl-D-aspartate (NMDA) receptors, which are thought to control the occurrence
      of long-term potentiation at individual synapses. Recent work in the hippocampus
      indicates that NMDA receptor activation does not necessarily lead to induction of
      long-term potentiation but instead may elicit a repertoire of distinct forms of
      synaptic plasticity including short-term potentiation or long-term depression.
      Furthermore, mechanisms exist such that the induction of long-term potentiation
      can be inhibited by modest activation of NMDA receptors. Experimental results are
      beginning to clarify the mechanistic relationships between these different
      phenomena, although much remains unknown. Whatever their underlying mechanisms,
      these additional forms of NMDA-receptor-dependent synaptic plasticity confer
      increased flexibility to neural circuits involved in information processing and
      storage.

PMID- 7509524
TI  - Prospects for clinically tolerated NMDA antagonists: open-channel blockers and
      alternative redox states of nitric oxide.
AB  - Several acute and chronic neurological diseases might be mediated, at least in
      part, via stimulation of excitatory amino acid receptors, such as the N-methyl-D
      aspartate (NMDA) receptor. Antagonists of excitatory amino acid receptors
      ameliorate neurotoxic damage in several animal models of these disorders. This
      review focuses on the potential for clinically tolerated NMDA receptor
      antagonists, with emphasis on agents that have been in clinical use for other
      conditions and that recently have been shown to inhibit NMDA receptor activity by
      a mechanism of open-channel block or redox modification.

PMID- 7509525
TI  - Outpatient visual laser-assisted prostatectomy under local anesthesia.
AB  - OBJECTIVE: Visual laser-assisted prostatectomy (VLAP) with a noncontact right
      angle delivery system recently has been introduced as a new treatment option for
      symptomatic outlet obstruction secondary to benign prostatic hyperplasia. The
      right-angle laser technology has numerous potential advantages over traditional
      transurethral resection of the prostate. These advantages include the feasibility
      of performing the VLAP procedure under local anesthesia without bleeding. We
      summarize our experience with VLAP performed with local anesthesia administered
      with periprostatic block. METHODS: This technique was employed in 46 men with
      symptomatic BPH as an outpatient procedure. All men were evaluated prior to
      surgery with flow rates, residual volume determinations, and AUA-6 symptom score
      analyses. Follow-up occurred at three and six months and included repeat measures
      of flow rates, residual volumes, and symptom scores. RESULTS: Mean AUA symptom
      scores and uroflow parameters significantly improved with six months' follow-up.
      No significant complications were encountered. CONCLUSIONS: VLAP under local
      anesthesia as an outpatient procedure is a promising treatment alternative for
      men with symptomatic benign prostatic hyperplasia.

PMID- 7509526
TI  - Correlation of prostate-specific antigen and prostate-specific antigen density
      with outcome of prostate biopsy.
AB  - OBJECTIVE: We attempt to correlate prebiopsy serum prostate-specific antigen
      (PSA) concentration and prostate-specific antigen density (PSAD) with histologic
      results of prostate biopsy. METHOD: Sixty-two consecutive patients underwent
      prostate biopsy because of elevated PSA greater than 4 ng/mL and/or abnormal
      findings on digital rectal examination (DRE). PSAD was calculated from dividing
      the serum PSA concentration by the prostate volume as determined by transrectal
      ultrasound (TRUS). PSA and PSAD were compared to biopsy outcome. RESULTS: The
      mean PSAD values of the cancer versus noncancer (benign prostatic tissue, benign
      prostatic hyperplasia, and prostatitis) groups were significantly different (p <
      0.019). However, there was great overlap in individual values. The mean PSA
      levels of the cancer versus noncancer groups also were significantly different (p
      < 0.0079). In patients with PSA levels between 4 and 10 ng/mL, 11 of 32 (34%) had
      positive biopsy findings for cancer. Eleven of 29 patients (38%) with normal DRE
      findings and elevated PSA levels (> 4 ng/mL) had positive biopsy findings for
      cancer. Seven of 19 patients (37%) with normal DRE findings and elevated PSA
      levels between 4 and 10 ng/mL had positive biopsy specimens for cancer.
      CONCLUSIONS: PSAD, though suggestive, is not definitive for cancer or noncancer.
      Patients with inflammation (prostatitis) present in their biopsy specimens have
      serum PSA levels and PSAD values intermediate between those with benign tissue
      (without inflammation) and cancer. We think that prostate biopsy is important in
      patients with PSA levels between 4 and 10 ng/mL even if their DRE result is
      normal, as our data indicate that over one third of these patients harbor
      detectable prostate cancer.

PMID- 7509527
TI  - Massive locally extensive prostate cancer.
AB  - A massive, locally extensive adenocarcinoma of the prostate (2,246 ccm)
      presenting as constipation and a palpable abdominal mass, was treated with
      androgen deprivation resulting in a 94 percent reduction in tumor size, and
      relief of symptoms. Serum prostate-specific antigen was reduced from 4,029 to 0.4
      ng/mL, after hormonal therapy was combined with radiation treatments for local
      disease control.

PMID- 7509528
TI  - Second-generation delivery systems for laser prostatic ablation.
AB  - OBJECTIVE: To assess the effectiveness of a second-generation laser delivery
      system (Side-Fire) in the treatment of benign prostatic hyperplasia (BPH).
      METHODS: Thirty-three patients with documented BPH were treated and evaluated pre
      and post-operatively with a follow-up period of twelve to thirty-six weeks.
      RESULTS: There was marked improvement demonstrated at three months post lasing in
      all patient outcome parameters (symptom score, flow rate, and post-void residual
      volume) using the new Side-Fire right-angled delivery system. CONCLUSION: Side
      Fire catheter laser ablation therapy produces an excellent transition zone
      ablation in established BPH.

PMID- 7509529
TI  - HCG and measurement of their subunits.

PMID- 7509530
TI  - Visual laser ablation of prostate.

PMID- 7509531
TI  - Proceedings of the 3rd International Conference on Benign Prostatic Hyperplasia,
      Prostate and Urothelial Cancer. Orlando, Florida, February 25-27, 1993.

PMID- 7509532
TI  - Hyperthermia as a treatment modality in benign prostatic hyperplasia.
AB  - OBJECTIVE: To review the current status of hyperthermia (heating the prostate up
      to 45 degrees C) as a treatment modality for benign prostatic hyperplasia (BPH).
      METHODS: Hyperthermia versus thermotherapy is defined, the techniques and
      equipment are presented, and the current English literature regarding safety and
      efficacy is reviewed. RESULTS: Both transrectal and transurethral heat
      applications are very safe procedures. Most studies evaluating the efficacy have
      been nonrandomized and uncontrolled. The 50-70 percent symptom improvement rate
      should be compared with the natural history of the disease and the considerable
      placebo effect. The few controlled studies produced contradictory results.
      CONCLUSIONS: At the present time, hyperthermia has not been shown, in
      scientifically well-designed studies, to be a treatment modality with measurable
      and durable outcome in BPH.

PMID- 7509533
TI  - High-intensity focused ultrasound in the treatment of prostatic tissue.
AB  - OBJECTIVE: Beginning in 1987, high-intensity focused ultrasound was investigated
      in the canine model to determine the feasibility of destroying prostate tissue.
      After demonstrating the ability to ablate prostate tissue reliably in a canine
      model, a 15-patient pilot clinical study was undertaken at Indiana University in
      the fall of 1992. This pilot study was undertaken to assess the safety in the
      human clinical situation, as well as to give some early efficacy results.
      METHODS: The early canine feasibility studies were conducted via a suprapubic
      extracorporeal approach using two separate transducers, one for imaging and the
      other for therapy. Subsequent to this, a transrectal probe, which had the dual
      capability of both imaging and therapy, was developed and used to treat canine
      prostates in a formal, "good laboratory practice" study to determine the safety
      of this technology prior to beginning treatment of human benign prostatic
      hypertrophy. RESULTS: The formal canine studies demonstrated that prostatic
      tissue could be reliably ablated in the therapy zone. The dosimetry and duty
      cycle required to ablate canine prostatic tissue effectively was also determined
      in this study. The study also demonstrated that the prostatic tissue could be
      ablated without injury to the intervening rectal tissue or periprostatic tissue.
      The human pilot study has also demonstrated safety of high-intensity focused
      ultrasound, as well as early efficacy. CONCLUSIONS: These early clinical results
      are encouraging, but assessment of efficacy will require a randomized study
      comparing high-intensity focused ultrasound to sham and to transurethral
      prostatectomy. This multicenter trial is currently planned.

PMID- 7509534
TI  - How to use prostate-specific antigen.
AB  - OBJECTIVE: To determine if prostate-specific antigen (PSA) is the most effective
      analyte for diagnosing, staging, and monitoring prostatic carcinoma. METHODS:
      This article reviews what PSA is and how it can be used to detect clinically
      significant carcinomas as well as its application in managing patients after
      radical prostatectomy, radiation therapy, and androgen deprivation therapy.
      RESULTS: PSA screening results in increased detection of localized disease. In
      individual patients a serum PSA level is not a good indicator of pathologic
      stage; however, a serum PSA level of greater than 10 ng/mL is associated with a
      higher incidence of extracapsular disease. Asymptomatic patients with newly
      diagnosed untreated prostate cancer and a serum PSA level less than 10 ng/mL do
      not need to undergo staging radionuclide bone scan. Elevated serum PSA is
      generally the first indicator of "persistent disease" after radical prostatectomy
      and radiation therapy. In androgen deprivation the PSA nadir is an important
      indicator of response to therapy. CONCLUSIONS: PSA is the most accurate tumor
      marker in oncology. This analyte can be successfully used to diagnose, stage, and
      monitor prostatic carcinoma.

PMID- 7509535
TI  - Androgen deprivation prior to radical prostatectomy for T2b and T3 prostate
      cancer.
AB  - OBJECTIVE: In an effort to improve on the results of radical prostatectomy for
      clinical stages T2b and T3 prostate cancer, a selected group of patients received
      androgen deprivation for three to sixteen months prior to surgery. METHODS:
      Fifteen men with clinical T2b and 22 with small T3 tumors received a luteinizing
      hormone-releasing hormone analog (n = 34) or a bilateral orchiectomy (n = 3)
      three to sixteen months prior to radical retropubic prostatectomy. The prostate
      was evaluated with particular attention to tumor grade, presence of extracapsular
      extension, tumor at the inked margin, seminal vesicle invasion, and tumor in the
      lymph nodes. RESULTS: No patient had clinical or chemical (prostate-specific
      antigen [PSA]) progression during androgen deprivation. The PSA level declined a
      mean 90 percent and remained above 4 ng/mL in only two patients. The prostate
      volume decreased an estimated 30-50 percent. Prostate cancer at the inked margin
      was found in 15 (41%) and seminal vesicle involvement in 11 (30%) patients. Five
      (14%) had tumor in regional lymph nodes. There was no difference in regard to
      positive margins or lymph node metastases between those clinically staged as T2b
      and those preoperatively staged as T3. Fourteen patients have received adjuvant
      therapy (13 androgen deprivation, one radiation therapy). None has progressed
      (mean follow-up, 38.4 months). Of 23 who did not receive immediate additional
      therapy, six (26%) had progression, as was evident from an increase in PSA and
      have since been treated. Only one continued to progress. Thirty-five of the 37
      patients are alive. Seventeen (46%) are tumor free (PSA < 0.4 ng/mL) without
      further androgen deprivation. CONCLUSIONS: Only a prospective randomized trial
      can determine whether androgen deprivation prior to radical prostatectomy has a
      role. The results from this trial are encouraging for several reasons. The
      prostate is much smaller as a result of androgen deprivation and this may
      facilitate surgery. Although the great majority of these patients were expected
      to be margin positive, 60 percent had negative margins and only 14 percent had
      positive lymph nodes.

PMID- 7509536
TI  - Endocrine therapies for symptomatic benign prostatic hyperplasia.
AB  - OBJECTIVE: To provide a comprehensive overview of the various endocrine therapies
      being developed and investigated for the treatment of symptomatic benign
      prostatic hyperplasia (BPH). METHODS: Peer-reviewed reports in the medical and
      urologic literature were examined for pertinent information relating to the role
      of luteinizing hormone-releasing hormone (LHRH) agonists, antiandrogens, 5 alpha
      reductase inhibitors, and aromatase inhibitors in the management of BPH. Special
      attention was given to the scientific rationale and clinical results for each
      therapy. RESULTS: LHRH agonists, antiandrogens, and 5 alpha-reductase inhibitors
      all reduce the androgenic stimulation to the prostate gland. In doing so, they
      decrease prostate size by 25 percent, but cause a modest improvement in symptom
      score (3-4 points) and peak urinary flow rate (approximately 2.5 mL/sec). All of
      these therapies cause a significant decrease in the serum prostate-specific
      antigen (PSA) concentration, and an effect is maintained as long as the treatment
      is continued. Side effects are most pronounced for the LHRH agonists, in which
      impotency and decreased libido are universal phenomena, and least significant for
      the 5 alpha-reductase inhibitors. Aromatase inhibitors eliminate the estrogenic
      stimulation to the prostate gland. Although substantial evidence exists to
      support the role of estrogens in the development and maintenance of BPH, no data
      from large-scale randomized clinical trials are available to document the
      clinical usefulness of aromatase inhibitors in the treatment of symptomatic BPH.
      CONCLUSIONS: Medications that produce a state of androgen deprivation can reduce
      the static component of BPH. Of these agents, the 5 alpha-reductase inhibitors
      have the greatest promise because of their low toxicity profile. The role of the
      aromatase inhibitors in the treatment of BPH remains to be determined.

PMID- 7509537
TI  - Control of sheep scab.

PMID- 7509538
TI  - Immunogens of bovine viral diarrhea virus.
AB  - Bovine viral diarrhea virus (BVDV) is a ubiquitous pathogen of cattle that
      induces economically important diseases affecting multiple organ systems. In the
      United States, over 150 biological products are licensed for control of BVDV.
      These products contain live or killed BVDV, and many products contain other
      viruses or bacteria. Potency tests for these vaccines are based on animal
      inoculation and serology. For live virus vaccines, titration of viral infectivity
      in cell culture is an accepted alternative to animal inoculation. The immunogens
      in a killed virus vaccine may be measured by enzyme linked immunoabsorbent assay.
      Immunogens of BVDV that stimulate a protective immune response have not been
      conclusively identified. Epitopes on a putative viral envelope glycoprotein,
      gp53, are involved in viral neutralization. Other viral glycoproteins, gp48 and
      gp25, are immunogenic but epitopes on these proteins do not stimulate production
      of antibodies that efficiently neutralize virus. Progress in developing
      meaningful in vitro assays for quantitation of BVDV immunogens awaits
      identification of viral proteins that stimulate a protective immunity.

PMID- 7509539
TI  - Immunogens of encephalitis viruses.
AB  - The equine encephalitis viruses are members of the genus Alphavirus, in the
      family Togaviridae. Three main virus serogroups represented by western (WEE),
      eastern (EEE) and Venezuelan equine encephalitis (VEE) viruses cause epizootic
      and enzootic infection of horses throughout the western hemisphere. All equine
      encephalitis viruses are transmitted through the bite of an infected mosquito.
      The first equine encephalitis virus vaccines were produced by virus inactivation.
      Problems with inadequate inactivation, which may have caused a major
      epidemic/epizootic of VEE in central America and Texas in the 1970s, led to the
      development of a live attenuated VEE virus vaccine (TC-83) derived by cell
      culture passage. Inactivated vaccines are still used to prevent equine infections
      with WEE and EEE viruses. Alphaviruses are small single stranded, positive sense
      RNA viruses. The 12000 nucleotide genome is enclosed in an icosahedral
      nucleocapsid composed of multiple copies of the capsid (C) protein. The virion is
      enveloped. The membrane is modified by the insertion of heterodimers of two
      glycoproteins: E1 and E2. Monoclonal antibody analysis of the surface
      glycoproteins have provided a detailed understanding of important protective
      antigens. Recent studies comparing gene sequences from virulent and avirulent VEE
      viruses have begun to delineate mechanisms of alphavirus attenuation.

PMID- 7509540
TI  - Canine cutaneous mast cells dispersion and histamine secretory characterization.
AB  - In view of the high incidence of canine cutaneous atopic disease and the
      relevance of mast cells to its pathogenesis, it was considered important to
      isolate firstly cutaneous mast cells from normal dog skin and to assess the
      histamine secretory activity, as this can be further used as a tool for the study
      of canine skin mast cell pharmacology in cutaneous atopy. The procedure for
      canine dermal mast cell dispersion following a skin enzymatic digestion (as for
      previous human skin mast cell dispersion methods) is described in detail. The
      number of canine cutaneous mast cells yielded per gram of skin was 2.31 +/- 0.21
      x 10(5) representing 1.00% of the total cutaneous cells. The total histamine
      content per mast cell is 4.93 +/- 0.39 pg. Net histamine release owing to
      stimulation by calcium ionophore A23187 (1 microM) and concanavalin A (1 mg ml-1)
      was respectively 32.17 +/- 3.56% and 20.39 +/- 2.41% of the total amount per
      cell. Viability and reactivity to both stimuli of dispersed cutaneous mast cells
      were similar to the results found in humans. The present study allows further
      research on the role of mast cells immunopharmacology in allergy by investigation
      of cells isolated from canine skin in naturally occurring or experimentally
      induced atopy in the dog to be undertaken.

PMID- 7509541
TI  - p53 and erbB-2 protein overexpression are associated with early invasion and
      metastasis in bladder cancer.
AB  - Overexpression of p53 and erbB-2 was studied by immunohistochemistry in formalin
      fixed tissue samples of 179 patients with transitional cell carcinoma of the
      urinary bladder. p53 immunostaining was strongly correlated with tumour stage (P
      < 0.0001). This was driven by a marked difference in p53 expression between pTa
      (37% positive) and pT1 (71%) tumours, while there was no difference between pT1
      and pT2-4 tumours. Similarly, a strong overall association between p53 expression
      and grade (P < 0.0001) was driven by a marked difference between grade 1 (28%)
      and grade 2 tumours (71%), and there was no significant difference between grade
      2 and grade 3 tumours. Surprisingly, the frequency of erbB-2 overexpression was
      higher in pT1 tumours (74%) than in either pTa (49%; P = 0.0265) or pT2-T4 (56%;
      P = 0.0645) tumours. Both p53 and erbB-2 expression was also associated with
      metastasis. Metastases were found in 77% of patients with p53 positive primary
      tumours, but in only 50% of the patients with p53 negative primary tumours (P =
      0.022). Metastases were found in 66% of patients with erbB-2 positive primaries,
      but in only 37% of the erbB-2 negative primaries (P = 0.020). Of 32 patients with
      positivity for both p53 and erbB-2, 84% developed metastases, as compared to 49%
      of patients with positivity for either one or neither positive (P = 0.002). We
      conclude that both p53 and erbB-2 overexpression are associated with early
      invasion in bladder cancer. Furthermore, p53 and erbB-2 may be important
      predictors for metastasis.

PMID- 7509544
TI  - "Symbiotic tissue transfer"--a new concept in reconstructive plastic surgery.
AB  - A new hypothesis of "symbiosis" in reconstructive surgery is introduced, which
      has been used for single stage reconstruction of a metacarpal hand. The concept,
      technique and its use, along with it's merits are detailed.

PMID- 7509542
TI  - Occurrence of cell death (apoptosis) in prostatic intra-epithelial neoplasia.
AB  - The aim of our study was to assess the frequency and location of apoptotic bodies
      (ABs) in haematoxylin and eosin-stained sections of prostatic intraepithelial
      neoplasia (PIN) and then to compare the patterns with those in benign prostatic
      hyperplasia (BPH) and prostatic invasive adenocarcinoma (PAC). ABs were
      identified in all epithelial cell layers of the ducts, acini and tumour islands,
      as well as in the lumina contained in such structures. In the epithelial cell
      layers, ABs were found in general in the intercellular space and occasionally in
      the cytoplasm of epithelial cells. The frequency of ABs increased from BPH
      through PIN up to PAC. The proportions of ABs in PIN lesions of low grade
      (PINlow) and high grade (PINhigh) were greater than in BPH, the values decreasing
      from the nuclei in the basal position towards those in the luminal layer. In
      PINlow, the mean category values were 0.85% (standard error, SE, 0.311%) in the
      basal, 0.623% (SE 0.065%) in the intermediate and 0.474% (SE 0.138%) in the
      luminal position. In PINhigh, the mean category values were 1.006% (SE 0.16%) in
      the basal position, 0.713% (SE 0.182%) in the intermediate and 0.618% (SE 0.172%)
      in the luminal position. The proportions of ABs in adenocarcinoma with cribriform
      pattern decreased from the basal towards the luminal layer, as for PIN: 1.806%
      (SE 0.346%) in the basal position, 1.15% (SE 0.172%) in the intermediate and
      0.886% (SE 0.137%) in the luminal position. In the solid/trabecular
      adenocarcinomas, the mean category value in the cell layer adjacent to the stroma
      was 2.154% (SE 0.203%), whereas in the other cell layers it was 2.052% (SE
      0.239%). In small and large acinar adenocarcinomas, the proportions of positive
      nuclei were 1.022% (SE 0.1%) and 0.922% (SE 0.163%), respectively. The evaluation
      of the frequency and location of ABs gives accurate information on cell death in
      PIN in comparison with BPH and PAC.

PMID- 7509543
TI  - [Calcitonin--action, use, preparations].

PMID- 7509545
TI  - Prefabrication of a skin axial flap in experiment.
AB  - Flap prefabrication was studied on the rat thigh by implanting femoral vessels
      into the flap's subcutaneous tissue. The aim of the experiment was to determine
      optimal prefabrication time, and to monitor, using contrast staining, the
      dynamics and morphology of the neovascularization process. The minimal time for
      successful prefabrication was 14 days in our experimental model. The potential of
      physiological and pharmacological regulation of the process of capillary
      neoformation is discussed. A successful attempt at free transfer of a
      prefabricated flap to the contralateral thigh and at femoral vessel anastomosis
      by microsurgery was also made as part of the experiment.

PMID- 7509546
TI  - The radial forearm flap: experiences with the extraordinary procedure.
AB  - Radial forearm flap has been increasingly used universally and is now a routine
      in most plastic surgery units. We developed the technique of Extracorporeal
      transfer of this flap for the benefit of those who do not have approach to the
      microsurgical methods. We at the same time used it as an Island flap and as a
      free flap depending upon the requirements and the feasibility of its transfer.
      Since 1985 till now we have used 40 such flaps for a variety of defects, such as
      for head and neck reconstruction including that of maxilla, for intraoral
      reconstructions, upper and lower extremity reconstruction, penile and oesophageal
      reconstructions. We present our experience of past 6 years on 40 flaps.

PMID- 7509547
TI  - Reconstruction of the frontal region with skull bone grafts.
AB  - Cranial bone grafts play a steadily increasing role as the dominant material used
      for reconstruction of defects within the frontal region. Both clinical experience
      and experiments on animals provided evidence that they showed a much smaller
      degree of resorption and that their cutting was associated with a markedly lower
      frequency of complications. Cranial bone grafts were used for the reconstruction
      of frontal defects in 17 patients. The results assessed six years after surgery
      disclosed a very slight degree of resorption in the presence of very good
      functional and cosmetic effects.

PMID- 7509548
TI  - Late results of the surgical treatment of complete unilateral cleft lip and
      palate: soft tissue characteristics.
AB  - Sixty-one UCLP patients at 17-20 years of age treated in childhood by the same
      surgeon (Krauss) were invited for check-up examination to evaluate the late
      results of the surgical treatment. In the patients, the cleft lip was closed by a
      modified Le Mesurier procedure at 6-9 months of age and the cleft palate by a
      modified Veau procedure at 3-4 years of age. The "normal face" appearance showed
      69% of the patients. More than one third of the population had successfully
      corrected nose deformities after the primary operation. In the most cases, the
      lip was also restored satisfactorily during the first treatment. Regular border
      between the lip and vermilion was observed in 62% of cases. The correct shape of
      hard palate was also found in 62% of the patients. The soft palate was well
      reconstructed in 92% of cases. In the most cases (95%), the speech was correct
      although the cleft palate was closed relatively late. The late results of the
      treatment can be considered satisfactory.

PMID- 7509549
TI  - Effects of premaxillary setback and of prolongation of the columella on the
      configuration of the facial profile in complete bilateral cleft lip and palate.
AB  - Roentgen-cephalometric studies were carried out in 26 adult males with complete
      bilateral cleft lip and palate. They were subdivided two times in two subgroups,
      with and without premaxillary setback, and with and without prolongation of the
      columella. The subgroups were compared mutually, as well as with a group of
      controls including 50 males matched in age. Premaxillary setback during childhood
      resulted in a more marked retrusion of the maxilla in adulthood. A simultaneous
      slighter oral slope of the premaxilla led to a normalization of the upper face
      height. Skeletal deviations acted on the configuration of the soft profile, in
      particular of the nasolabial transition: the slope of the columella towards the
      profile was reduced and so was the nasolabial angle. Thus the region appeared
      more markedly sunken. This surgical procedure should be used only in an
      exceptional situation in a small or posteriorly rotated mandible. Prolongation of
      the columella resulted in an excessive nasal depth. This was not caused by an
      adequate elevation of the tip of the nose which corrected a flattening of the
      tip, but rather by the sunken upper lip. An unfavourable effect exerted also a
      larger deepening of the nasolabial transition after a prolongation of the
      columella. However a slighter prolongation of the columella did not allow a
      sufficient elevation of the nasal tip. It is therefore necessary to seek a
      compromise.

PMID- 7509550
TI  - The effect of two-stage palatoplasty on facial development in unilateral cleft
      lip and palate.
AB  - Measurements on X-ray films were used for the assessment of facial development in
      24 individuals with complete unilateral cleft lip and palate, ranging in age from
      10 to 11 years and operated upon in two stages. The suture of the velum was
      performed simultaneously with cheiloplasty at the age of 7 months, the suture of
      the hard palate followed at the age of 6 years. They were compared with a series
      of 27 individuals with the same type of cleft who were subjected to one-stage
      closure of the palate at the age of 4 years. But for the more favourable
      occlusion of incisors after two-stage palatoplasty, which was due to the more
      intense orthodontic therapy, these two series showed no differences in facial
      growth and development. The delay of surgical repair of the hard palate by two
      years did not improve the growth and development of jaws. However, it is not
      possible to exclude favourable effects of a delay of the suture of hard palate
      into a substantially more mature age.

PMID- 7509555
TI  - [Surgical treatment of metastases of the hip].

PMID- 7509553
TI  - Our experience with the technique of areolar rotation in reduction mammaplasty.
AB  - In the article, the authors present a relatively uncommon method employed for
      breast reduction and moulding in gigantomastia. They examine the benefits of the
      surgical technique based on areolar rotation with a wide superior-lateral dermal
      areolar flap. The authors point out the fact that postoperative blood supply to
      the areolas is very good while their sensitivity is preserved.

PMID- 7509552
TI  - Microcirculation flow alterations in burn wounds.

PMID- 7509551
TI  - Classification of deep burn injuries--analyses of 117 cases.
AB  - A new system of classification, index of deep burn injuries (IDBI), was proposed
      in this paper. Using this system, we investigated 304 burn sites in 117 cases, of
      which 94.1% were repaired with the GCM with a satisfactory result. The IDBI of
      the 304 burn sites is in direct proportion to the severity and extent of burn
      injury and inverse ratio to the results. Analyses performed in this group
      suggested that the IDBI has many significances, which include: 1, making a
      correct diagnosis; 2, providing decided repair indications; 3, indicating the
      prognosis; 4, providing a reliable method for further investigation in the burn
      field. The standard of IV degree burn is equal to or more than 2 of IDBI.

PMID- 7509554
TI  - The role of instrumental diagnostic methods in the staging of Sudeck's disease.
AB  - Forty patients with Sudeck's atrophy were assessed in order to evaluate the
      diagnostic accuracy of x-ray, scintigraphy and telethermography in staging the 3
      phases of the disease. The dynamic and early static phases of scintigraphy were
      the most sensitive and specific instrumental tests for detecting the early stage,
      whereas telethermography was fairly sensitive but not very specific. Radiographic
      examination was not sensitive in detecting slight changes in bone density, but it
      was the most reliable index for recognizing the transition to stage II of the
      disease. Moreover, it was possible to confirm that the late static phase of
      scintigraphy is the index which is best related to bone metabolism.

PMID- 7509556
TI  - [Surgery of bony metastases of the limbs].

PMID- 7509557
TI  - Instability of hybrid plasmids in Bacillus subtilis.
AB  - We studied the mechanisms responsible for instability of hybrid derivatives of
      staphylococcal R plasmids in B. subtilis cells. Four pBCH plasmids were
      constructed from staphylococcal chloramphenicol-resistance plasmid pC756 ligated
      with pBR322 or pUC8 vectors, and two pAEC plasmids contained pC756 plasmid, erm
      gene from S. aureus pE3692 and pBR322 plasmid vector. The level of instability of
      these recombinant plasmids was clearly related to their sizes, the larger
      derivatives were segregationally highly unstable. The four hybrid pBE plasmids
      constructed from erythromycin-resistant pE3692 plasmid or its deletion derivative
      and pBR322 vector were poorly maintained in B. subtilis rec+ strain in comparison
      with the B. subtilis (recE4) strain. Moreover, the absence in pBE-hybrids of a
      part of palA sequence led to considerable reduction of plasmid stability in B.
      subtilis cells. However, the clones of B. subtilis harbouring pBE plasmids
      integrated into the bacterial chromosome presented much higher stability of the
      plasmid erm gene than the clones maintaining autonomously replicating plasmids.

PMID- 7509559
TI  - Integration host factor (IHF) applied for partial digestion by restriction
      endonucleases in large DNA molecules (IARC procedure).
AB  - The IHF protein of Escherichia coli was successfully used in IHF-mediated
      Achilles' Heel Cleavage (IHF-AC) technique (Koob et al., 1988; Kur et al., 1992),
      and leads to the generation of very rare restriction sites in large DNA
      molecules. The first step of this procedure is methylation of DNA in the presence
      of IHF, when the overlapping ihf/restriction sites are protected from
      methylation, and in the second step the DNA is cut by the cognate restriction
      enzyme. The aim of the present study is to develop a very exact and reproducible
      procedure to obtain only a few well-defined cuts with the IHF-pre-treated DNA,
      depending on the variety of all parameters. This technique (IARC, i.e., IHF
      assisted rare cutters) employs the restriction enzyme and only one auxiliary
      protein (IHF). The advantage of the IARC procedure is that no methylation is
      required (as opposed to the IHF-AC method). Using the IARC approach, the effects
      of various IHF concentrations were evaluated on cleaving the activity of the
      DraI, PacI, PmeI, and SwaI enzymes using DNA of phage lambda or the entire
      genomic 4.7-Mb DNA of E. coli. At low IHF concentrations only a few cut sites
      were eliminated by IHF binding, but at high IHF concentration, enzymes were able
      to cut in only one or several specific sites.

PMID- 7509558
TI  - Use of IHF--mediated Achilles' heel cleavage (IHF-AC) method for mapping ihf
      sites.
AB  - We have shown that Integration Host Factor of E. coli can successfully be used in
      the IHF-mediated Achilles' Heel Cleavage (IHF-AC) technique (Kur et al., 1992b),
      for generating rare natural cleavage sites. The first step of this procedure is
      methylation of DNA in the presence of IHF, when the overlapping ihf/restriction
      sites are protected from methylation, and in the second step the DNA is cut by
      the cognate restriction enzyme. The extent of cleavage could be controlled by
      varying the IHF:DNA ratio and temperature. The aim of the present study is to
      demonstrate that IHF-AC procedure might serve as a useful tool for finding new
      protein-binding sites which overlap known restriction sites. I have used this
      approach in conjunction with several MTases to find several other unknown IHF
      binding sites.

PMID- 7509560
TI  - Immunomodulatory activities of Nocardia opaca.
AB  - Nocardia lysozyme digest (NLD), a particulate fraction from Nocardia opaca, is
      able to induce antitumor activity to SaL-1 tumor cells (lung sarcoma) in Balb/c
      mice. In mice immunized with NLD inhibition of tumor growth and prolonged
      survival of tumor bearing animals was observed. Macrophages isolated from
      peritoneal cavity and stimulated with NLD release a few arachidonic acid
      metabolites, mostly PGE 2. Macrophages from tumor bearing mice are more sensitive
      to Nocardia antigens than normal. Both in vitro and in vivo experiments have
      documented that Nocardia is an active immunomodulator.

PMID- 7509562
TI  - Attempts at the further characterisation of exoprotease from Pseudomonas sp.
      strain S9.
AB  - The correlation between EPS release and exoprotease activity from Pseudomonas sp.
      was shown. The presence of added exoprotease was recognized by cells of
      Pseudomonas sp. strains S9 and B29 and was a factor inhibiting exoprotease
      synthesis de novo. Examined enzyme is a metalloprotein containing zinc with mass
      estimated at 60,000 daltons.

PMID- 7509561
TI  - Evaluation of the SOS chromotest for detection of genotoxic drugs.
AB  - In the present investigation, the SOS Chromotest with E. coli PQ37 was evaluated.
      The potential of the test to identify genotoxic properties of different
      cytostatics was examined. Only intercalating agents showed good activity. The SOS
      Chromotest appeared to be less effective than the Salmonella mutagenicity test in
      the detection of alkylating agents.

PMID- 7509563
TI  - Solid cell nests of the thyroid. A histologic and immunohistochemical study.
AB  - A histologic and immunohistochemical study was performed to identify the
      histogenesis of solid cell nests (SCN), which were found incidentally in 11
      thyroid glands obtained by surgery. Histologically, SCN consisted of small nests
      showing solid and cystic structures. Cystic features of SCN were found in 3 of
      the 11 cases (27%), with mucinous materials in their lumens. Some goblet cells
      were also present in three cases (27%). In one case, SCN were associated with
      lymphocyte aggregation. Immunohistochemical analysis using serial sections of the
      SCN showed that the cells comprising SCN were positive for calcitonin in 5 cases
      (45%), for carcinoembryonic antigen (CEA) detected using polyclonal antibody in
      11 (100%), for CEA detected using monoclonal antibody in 3 (27%), for calcitonin
      gene related peptide in 2 (18%), for chromogranin A in 5 (45%), and for keratin
      in 11 (100%). These antigens were expressed concomitantly in the same SCN, but
      the number and distribution of the positive cells for the antigens were different
      for each antigen in the same SCN in each case. These findings strongly support
      the view that SCN are derived from the ultimobranchial body. In addition, the
      biologic function to produce the antigens may vary greatly in individual cells
      comprising SCN.

PMID- 7509564
TI  - Genetic analysis of Hispanic individuals with cystic fibrosis.
AB  - We have performed molecular genetic analyses of Hispanic individuals with cystic
      fibrosis (CF) in the southwestern United States. Of 129 CF chromosomes analyzed,
      only 46% (59/129) carry delta F508. The G542X mutation was found on 5% (7/129) of
      CF chromosomes. The 3849 + 10kbC-->T mutation, detected primarily in Ashkenazi
      Jews, was present on 2% (3/129). R1162X and R334W, mutations identified in Spain
      and Italy, each occurred on 1.6% (2/129) of CF chromosomes. W1282X and R553X were
      each detected once. G551D and N1303K were not found. Overall, screening for 22 or
      more mutations resulted in detection of only 58% of CF transmembrane conductance
      regulator gene mutations among Hispanic individuals. Analysis of KM19/XV2c
      haplotypes revealed an unusual distribution. Although the majority of delta F508
      mutations are on chromosomes of B haplotypes, the other CF mutations are on A and
      C haplotypes at higher-than-expected frequencies. These genetic analyses
      demonstrate significant differences between Hispanic individuals with CF and
      those of the general North American population. Assessment of carrier/affected
      risk in Hispanic CF individuals cannot, therefore, be based on the mutation
      frequencies found through studies of the general population but must be adjusted
      to better reflect the genetic makeup of this ethnic group. Further studies are
      necessary to identify the causative mutation(s) in this population and to better
      delineate genotype/phenotype correlations. These will enable counselors to
      provide more accurate genetic counseling.

PMID- 7509566
TI  - Microorganism-induced or enhanced mediator release: a possible mechanism in
      organic dust related diseases.
AB  - Bacteria were found to trigger mediator release, including histamine, leukotriene
      B4, and prostaglandin D2. Furthermore, histamine release caused by allergens as
      well as by nonimmunological reactions was enhanced by bacteria, endotoxins, and
      spores from molds. Mediator release and its enhancement play a crucial role for
      bronchoconstriction and inflammatory events in the airways. These effects of
      allergens, microorganisms, and other noxious agents in dusts may, therefore, in
      concert be responsible for the symptoms in organic dust related diseases.

PMID- 7509565
TI  - Sephadex-induced granulomatous alveolitis in rat: effects of antigen
      manipulation.
AB  - A granulomatous alveolitis, with multinuclear cell formation combined with an
      eosinophilic peribronchiolitis, was achieved in rats by intratracheal
      administration of sephadex beads (G-200, Pharmacia, Sweden). The pattern of
      inflammation and the degree of postgranulomatous fibrosis were substantially
      dampened when the particles were dispersed by ultrasonification. The animals were
      analyzed with bronchoalveolar lavage and tissue morphology.

PMID- 7509567
TI  - Natural history of trisomy 18 and trisomy 13: II. Psychomotor development.
AB  - Developmental data were abstracted from medical records on 50 trisomy 18
      individuals ranging in age from 1 to 232 months and 12 trisomy 13 individuals
      ranging in age from 1 to 130 months. Data on the age when trisomy 18 and trisomy
      13 children achieved developmental skills were collected from a larger group of
      62 trisomy 18 individuals and 14 trisomy 13 individuals whose families filled out
      parent questionnaires. Developmental quotient (DQ), defined as developmental age
      divided by chronological age, averaged 0.18 for trisomy 18 and 0.25 for trisomy
      13. There was a dramatic drop in DQ from infancy to later childhood. The highest
      DQs and the greatest variation in DQs were in the first 2-3 years of life.
      Developmental ages in 7 skill areas were significantly different, with daily
      living and receptive language having the highest values and motor and
      communication skills having the lowest. When chronological age was taken into
      account, there was no significant difference in DQs in the same 7 skill areas,
      although there was a trend that was similar to the pattern of differences with
      developmental age. Older children could use a walker, understand words and
      phrases, use a few words and/or signs, crawl, follow simple commands, recognize
      and interact with others, and play independently. Walking and some toileting
      skills were also reported for trisomy 13. Although individuals with trisomy 18
      and trisomy 13 were clearly functioning in the severe to profound developmentally
      handicapped range, they did achieve some psychomotor maturation and always
      continued to learn.

PMID- 7509568
TI  - Mild growth retardation and developmental delay, microcephaly, and a distinctive
      facial appearance.
AB  - We describe a brother and sister from one family and a girl from a second,
      unrelated family; they have a syndrome of pre- and post-natal growth deficiency,
      developmental delay, a friendly personality, microcephaly, and a distinctive
      facial appearance marked by thick eyebrows, full cheeks, and a short nose with
      the columella inserted below the nasal alae. We think this is a new syndrome
      probably inherited as an autosomal recessive trait.

PMID- 7509569
TI  - Detection of fetal Turner syndrome with multiple-marker screening.
AB  - OBJECTIVE: Our purpose was to examine the ability of the multiple-marker
      screening test (maternal serum alpha-fetoprotein, human chorionic gonadotropin,
      unconjugated estriol, and maternal age) to detect fetal Turner syndrome. STUDY
      DESIGN: We reviewed 27,282 screening tests performed at our institution between
      July 1, 1990, and June 30, 1992. All cases in which fetal Turner syndrome was
      detected as a result of a positive Down syndrome screening test (Down syndrome
      risk > or = 1:190) or in which a positive screening test was obtained before an
      amniocentesis scheduled for other reasons were included. Serum marker levels,
      Down syndrome risk, and ultrasonographic findings were reviewed. To clarify the
      relative contributions of estriol and human chorionic gonadotropin to the
      positive screen, the risks were recalculated using only maternal serum alpha
      fetoprotein and hCG or maternal serum alpha-fetoprotein and estriol. RESULTS:
      Eight cases were identified. Four fetuses had cystic hygroma and hydrops, two had
      hygroma only, and two had no abnormality on ultrasonography. Both human chorionic
      gonadotropin and estriol contributed to the positive screen. CONCLUSION: The
      multiple-marker screening test appears to detect Turner syndrome, as well as
      trisomies 21 and 18.

PMID- 7509570
TI  - Quality of life after the menopause: influence of hormonal replacement therapy.
AB  - OBJECTIVE: Our purpose was to demonstrate the clinical efficacy and effect of
      hormone replacement therapy in menopause on quality of life. STUDY DESIGN: A
      randomized, open, 6-month comparison of hormone replacement therapy (estradiol
      transdermal system [Estraderm TTS] plus chlormadinone) and symptomatic treatment
      (verapipride) was performed. Analysis was by intention to treat. RESULTS: In 499
      postmenopausal women with moderate and severe symptoms enrolled by 101
      physicians, hormone replacement therapy was superior to symptomatic treatment on
      all assessments of quality of life and clinical efficacy. The effects were
      independent of the incidence of hot flushes. CONCLUSION: The effect of hormone
      replacement therapy on the quality of life of postmenopausal women was
      significantly superior to symptomatic treatment.

PMID- 7509571
TI  - Glycoprotein hormones and their common alpha-subunit stimulate prolactin
      production by explant cultures of human leiomyoma and myometrium.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of the
      gonadotropins luteinizing hormone, follicle-stimulating hormone, and human
      chorionic gonadotropin on prolactin production by human leiomyomas and
      myometrium. A secondary goal was to explore the effect of thyroid-stimulating
      hormone and the alpha-subunit common to all these glycoproteins in the same
      system. STUDY DESIGN: Explant cultures were established, and harvested medium was
      assayed for total protein and prolactin. Dose-response studies were performed
      with follicle-stimulating hormone, luteinizing hormone, and human chorionic
      gonadotropin. A second set of studies was conducted with a single dose of human
      chorionic gonadotropin, thyroid-stimulating hormone, and alpha-subunit. RESULTS:
      Gonadotropins, thyroid-stimulating hormone, and alpha-subunit all stimulated
      prolactin production in both leiomyoma and myometrium. Prolactin production was
      significantly higher in leiomyoma than in myometrium. A positive effect of time,
      dose, and gonadotropin treatment on prolactin production was seen in each tissue.
      There was no treatment effect on total protein secretion. CONCLUSIONS: All four
      glycoprotein hormones and their common alpha-subunit stimulate prolactin
      production. This appears to be a specific effect.

PMID- 7509572
TI  - The genomic basis of the beta-subunit of human chorionic gonadotropin diversity
      in triploidy.

PMID- 7509573
TI  - A comparison of structured sensorimotor therapy and child-centered activity in
      the treatment of preschool children with sensorimotor problems.
AB  - This study compared the benefits of a child-centered therapy approach emphasizing
      child-initiated play interactions within a structured therapy environment to
      those of a therapist-directed, structured sensorimotor therapy approach in 12
      preschool children with sensorimotor dysfunction. Each child received a pretest,
      8 weeks of intervention (A or B) provided once weekly for a 1-hr session, a
      retest, 8 weeks of intervention (B or A) provided once weekly, and a final
      retest. A case study methodology was used to evaluate outcome data. Structured
      sensorimotor therapy was more useful than child-centered therapy in promoting
      gross motor skills, functional abilities (i.e., self-care), and sensory
      integrative functions. Child-centered therapy appeared to promote fine motor
      skills better. Although there were no differences in the two therapies for gains
      in play, attention, and behavior, variables such as temperament, attentional
      abilities, family stress, severity of sensorimotor delay, and whether the child
      had received treatment before seemed to affect which therapy was more beneficial
      for behavior, play, and attention. The effect of the findings on therapeutic
      practice is discussed.

PMID- 7509574
TI  - Sarcomatoid carcinoma of the urinary bladder. Clinicopathologic analysis of 18
      cases with immunohistochemical and electron microscopic findings.
AB  - Sarcomatoid carcinoma is a rare tumor in the urinary bladder and accounts for
      approximately 0.3% of all bladder malignancies. In this study, the
      clinicopathologic findings of 18 cases are described. Distribution of sex and age
      and clinical symptoms are not distinctive from transitional cell carcinoma. The
      tumor behaves as a high-grade malignancy with advanced initial stage and
      unfavorable outcome. Surgery is the therapy of choice. Histological
      differentiation from true sarcoma may be difficult. Recognition rests on the co
      existence of an overt carcinomatous component or demonstration of the epithelial
      nature by immunohistochemistry or electron microscopy.

PMID- 7509575
TI  - Effect of ethanol exposure on circulating levels of insulin-like growth factor I
      and II, and insulin-like growth factor binding proteins in fetal rats.
AB  - Maternal ethanol (ETOH) exposure is associated with impaired fetal growth.
      Because insulin-like growth factors (IGFs) are thought to be important in the
      regulation of fetal somatic growth, we examined the influence of maternal ETOH
      exposure on fetal growth and plasma levels of IGF-I, IGF-II, and IGF binding
      proteins (IGFBPs) in the rat model. Control (A) dams were fed a standard rat chow
      ad libitum. ETOH (E) consuming dams were fed a 36% ETOH diet, and pair-fed (P)
      dams were fed isocaloric amounts of a control liquid diet. All animals were
      killed on day 20 of gestation. Plasma concentrations of IGF-I and -II were
      determined by radioimmunoassay after formic acid-acetone extraction and heat
      inactivation of IGFBPs. Levels of IGFBPs in fetal plasma were estimated by
      Western ligand blotting after protein separation by SDS-PAGE and electrotransfer
      to nitrocellulose. Membranes were probed with [125I]IGF-I, and IGFBPs were
      identified by autoradiography, quantified by scanning densitometry and results
      expressed relative to corresponding IGFBPs in control fetal plasma. Maternal
      weight gain from conception to 20 days of pregnancy was reduced for E compared to
      P and A dams (p < 0.05 E vs. P or A). The same pattern was reflected in fetal
      weight that tended to be lower in P compared with A pups, and was significantly
      reduced in E pups compared with both groups (p < 0.0001 E vs. P or A). Thus,
      fetal growth was more retarded in E animals despite equal caloric and protein
      intake by E and P dams.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509576
TI  - Granulocyte colony-stimulating factor prevents ethanol-induced impairment in host
      defense in septic rats.
AB  - Ethanol is a potent immunosuppressive agent that impairs neutrophil effector
      function. The purpose of this study was to determine whether granulocyte colony
      stimulating factor (G-CSF), a cytokine that increases neutrophil number and
      functional activity, could prevent the ethanol-induced impairment of
      antibacterial host defense. Rats were injected with human recombinant G-CSF for 2
      days. Eight hr after the last injection of G-CSF, animals were infused with
      ethanol (or saline) for 1 hr before the subcutaneous injection of live
      Escherichia coli. The infusion of alcohol was continued after the bacterial
      challenge and produced blood alcohol levels of 275-300 mg/dl. In control animals,
      the injection of E. coli resulted in a marked leukopenia. There was an influx of
      leukocytes into the subcutaneous space where the bacteria were injected, and
      neutrophil accumulation in tissues adjacent to the focus of infection (i.e.,
      dorsal skin and muscle). Based on myeloperoxidase activity, there was no
      detectable accumulation of neutrophils in other soft tissues. In acutely
      intoxicated rats, leukocyte migration to the inflammatory site was impaired, and
      the number of viable bacteria isolated from the subcutaneous pocket was markedly
      increased. G-CSF prevented the sepsis-induced leukopenia, increased the influx of
      neutrophils in to the infection site, reduced the number of bacteria in the
      subcutaneous lavage fluid, and decreased the incidence of bacteremia in ethanol
      treated rats when compared with rats not receiving G-CSF. These results
      demonstrate that G-CSF is a potent immunomodulator that stimulates neutrophil
      recruitment selectively to the site of infection and that can be used to
      ameliorate the ethanol-induced impairment in bacterial host defense.

PMID- 7509577
TI  - Immunocytologic analysis of nasal cells obtained by nasal lavage: a comparative
      study with a standard method of cell identification.
AB  - For evaluation of two methods of nasal cell identification, cell morphology and
      immunocytologic analysis, nasal lavage was performed in 16 healthy subjects and
      29 patients suffering from rhinitis. Nasal lavage smears were stained with May
      Grunwald-Giemsa (MGG), and cells were identified according to their structure as
      epithelial cells, neutrophils, lymphocytes, eosinophils, and metachromatic cells
      (basophils and mast cells). Immunocytologic analysis was performed with
      monoclonal antibodies by the immunoalkaline phosphatase method. The following
      monoclonal antibodies were used: CK1, EG2, and CD3, which identify epithelial
      cells, activated eosinophils, and T lymphocytes, respectively; CD15, which
      recognizes mature granulocytic cells; and CD14, which reacts with monocytes and
      macrophages. A significant difference was observed between the two methods in the
      number of identified epithelial cells, in both controls (64.6 +/- 7.8% with MGG,
      14.2 +/- 3.5% with CK1 analysis) and patients with rhinitis (56.9 +/- 7.6% with
      MGG, 18.2 +/- 3.7% with CK1 analysis). In contrast, no significant differences
      were found in eosinophil and neutrophil counts when the two methods were
      compared. After nasal allergic provocation, a significant increase in the number
      of eosinophils was observed with both methods in seven patients with rhinitis.
      The results of this study indicate that: 1) MGG staining is a useful method to
      identify the cells obtained by nasal lavage, and 2) immunocytologic analysis with
      monoclonal antibodies accurately identifies granulocytic cells, while only a low
      proportion of epithelial cells are detected, probably because anticytokeratin
      monoclonal antibody reacts only with viable cells.

PMID- 7509578
TI  - Immunoglobulin-G-dependent stimulation of guinea pig lung mast cells and
      macrophages.
AB  - Alveolar macrophages and mast cells isolated from guinea pig lung were passively
      sensitized with IgG1, IgG2, or serum obtained from guinea pigs actively
      sensitized with ovalbumin. The release of histamine by mast cells and of
      thromboxane A2 by alveolar macrophages upon ovalbumin challenge indicated that
      both antibodies and serum were capable of sensitizing these cells with similar
      effectiveness. Heating the serum at 56 degrees C for 4 h to inactivate IgE did
      not modify the antigen-dependent response of lung cells. These results suggest a
      predominant role for IgG in the allergic response of the guinea pig through the
      activation of different cell types such as lung mast cells and alveolar
      macrophages.

PMID- 7509579
TI  - Organization of the striatal projections from the rostral caudate nucleus to the
      globus pallidus, the entopeduncular nucleus, and the pars reticulata of the
      substantia nigra in the cat.
AB  - This study explores the organization of the striatal projections from the rostral
      caudate nucleus to the output nuclei of the basal ganglia in the cat. Tracer
      deposits were stereotaxically injected in different dorsoventral, mediolateral,
      and rostrocaudal sectors of the head of the caudate nucleus using horseradish
      peroxidase (HRP) conjugated with wheat germ agglutinin (HRP-WGA) either alone or
      mixed with free HRP. After the injections, a detailed analysis of the terminal
      labeling was carried out within the globus pallidus (GP), the entopeduncular
      nucleus (Ep), and the substantia nigra (SN) pars reticulata (SNR). Our findings
      illustrate how different dorsoventral, mediolateral, and rostrocaudal parts of
      the rostral caudate nucleus project primarily to similarly positioned but
      spatially segregated parts of GP. The striatoentopeduncular pathway was also
      organized topographically, but there was overlapping by projections from
      different parts of the rostral caudate nucleus. Areas of topographical
      segregation and zones of overlap were detected in the organization of the
      striatal projections from the rostral caudate nucleus to SNR. These results raise
      the possibility of distinct striatal actions upon different sectors of the output
      nuclei of the basal ganglia and, indirectly, upon their targets in the thalamus
      and brainstem.

PMID- 7509580
TI  - Neoformation of blood vessels in association with rat lung fibrosis induced by
      bleomycin.
AB  - We have used intratracheal instillation of bleomycin in rats to study the
      microanatomical changes of blood vessels associated with lung fibrosis. Bleomycin
      is a toxic cytostatic drug employed in classical models of lung fibrosis. Wistar
      rats were submitted to intratracheal injection of 1.5 units of bleomycin and
      sacrificed 2.5 months later, a timing when marked fibrosis of the lung is
      observed. We casted the vascular tree of the rat lungs by perfusion with a
      methacrylate resin. These casts were studied by scanning electron microscopy.
      Lung tissue was also studied by light microscopy and thin section electron
      microscopy. The major vascular modifications observed in the bleomycin-treated
      rats were: (1) neoformation of an elaborate network of vessels located in the
      peribronchial domains of the lung, and (2) distortion of the architecture of
      alveolar capillaries. By light microscopy, it was clear that the newly formed
      vascular network was located in regions of fibrosis (which in the resin casts
      were digested away). These neoformed vessels appeared to originate from bronchial
      arteries. Thin section electron microscopy revealed that endothelial cells of the
      neoformed vessels were plump, presented large nuclei, and showed numerous
      pinocytotic vesicles that were also observed in subendothelial pericytes. The
      alveoli of the bleomycin-treated rats were heterogeneous in size and shape in
      contrast with the homogeneity of alveoli of control animals. The alveolar
      capillaries of fibrotic lungs appeared to occupy a larger volume of the alveolar
      wall than alveolar capillaries of control rats. Our findings indicate that lung
      fibrosis encompasses marked changes of the vascular system, namely, the
      neoformation of vessels and the rearrangement of alveolar capillaries. These
      structural changes suggest that fibrotic transformation of the lung is associated
      with the local generation of angiogenic stimuli.

PMID- 7509581
TI  - Intense vascular sprouting from rat femoral vein induced by prostaglandins E1 and
      E2.
AB  - The formation of new capillaries from the rat femoral vein was specifically
      explored to assess whether venous vessels of this caliber may participate in the
      process of angiogenesis. Prostaglandins of the E series (PGE1 and PGE2) were
      administered into the soft connective tissue surrounding the rat femoral vessels
      as angiogenic inducers. In these conditions, between 2 and 7 days, a great number
      of new capillaries were observed in the media of the femoral vein, arising from
      the endothelial cells (EC) in the intima. The events of the capillary growth from
      the femoral vein included EC activation, local degradation of the basal membrane
      followed by migration and proliferation of EC, solid sprout formation with
      posterior canalization, development of a new basal membrane, and appearance of
      pericytes around the new capillary. Although numerous vascular buds were also
      observed arising from the small venules and capillaries in the periadventitial
      tissues, they were separated at first from those in the media of the femoral vein
      by the venous adventitia. Later, connections were observed between both newly
      formed microcirculations. The present study shows the capacity of PGE1 and PGE2
      in the extravascular position of inducing capillary sprouting from veins.
      Furthermore, the observations provide greater evidence that vessels with
      characteristics similar to those of the rat femoral vein may contribute to
      angiogenesis, on occasion with an intense neovascularization. This fact may be of
      interest for the establishment of a functional circulation after angiogenesis by
      anastomoses of the new capillaries with those arising from pre-existing vessels
      of greater caliber than the venules.

PMID- 7509583
TI  - [Digital library for archiving files of radiology and medical imaging].
AB  - The Conseil des Enseignants de Radiologie de France in collaboration with the
      Ilab-TSI company and Schering laboratories has developed a computer programme
      allowing the storage and consultation of radiological teaching files. This
      programme, developed on Macintosh from standard Hypercard and Quicktime
      applications, allows, in consultation mode, the multicriteria search and
      visualisation of selected radiological files. In the author mode, new files can
      be included after digitalizing the author's own images or after obtaining images
      from another image library. This programme, which allows juxtaposition of
      digitalised radiological files, is designed to be extremely open and can be
      easily combined with other computer-assisted teaching or computer-assisted
      presentation applications.

PMID- 7509582
TI  - Comparison of techniques for diagnosis of proliferative enteritis of swine.
AB  - In an abattoir-based case-control study, histologic, and macroscopic examination
      of porcine intestines at slaughter and 2 molecular assays were compared for use
      as diagnostic tests of proliferative enteritis (PE). Fecal samples and intestinal
      specimens were collected from pigs with grossly thick ileum and from clinically
      normal pigs at slaughter. Tissue specimens were fixed in neutral buffered 10%
      formalin, and sectioned. Sections stained with H&E were examined for
      proliferative lesions by a pathologist unaware of the group to which the pig had
      been assigned on the basis of results of gross examination. Adjacent tissue
      sections, stained with Warthin-Starry (silver) stain, were examined for presence
      of the intracellular bacterium of PE, ileal symbiont (IS)-intracellularis, in the
      enterocytes of the intestinal crypts by the senior author, who was unaware either
      of the group to which the pig had been assigned or diagnosis by the pathologist.
      Bacterial DNA was extracted from the fecal samples and assayed by dot-blot
      hybridization and polymerase chain reaction (PCR) for presence of IS
      intracellularis DNA, without knowledge of results of the other examinations. The
      PCR assay for IS-intracellularis was a specific and sensitive diagnostic test for
      PE, and dot-blot hybridization was sensitive, but was less specific. Macroscopic
      examination of intestines at slaughter was a sensitive, but not specific, test.
      Association between IS-intracellularis and proliferative lesions was
      statistically examined in the same study. There was a highly significant (P =
      0.0078) association between presence of naturally acquired proliferative lesions
      and intracellular infection induced by IS-intracellularis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7509584
TI  - Detection of mycoplasma contamination in cell cultures by a mycoplasma group
      specific PCR.
AB  - The suitability of a 16S rRNA-based mycoplasma group-specific PCR for the
      detection of mycoplasma contamination in cell cultures was investigated. A total
      of 104 cell cultures were tested by using microbiological culture, DNA
      fluorochrome staining, DNA-rRNA hybridization, and PCR techniques. A comparison
      of the results obtained with these techniques revealed agreement for 95 cell
      cultures. Discrepant results, which were interpreted as false negative or false
      positive on the basis of a comparison with the results obtained with other
      methods, were observed with nine cell cultures. The microbiological culture
      technique produced false-negative results for four cell cultures. The
      hybridization technique produced false-negative results for two cell cultures,
      and for one of these cell cultures the DNA staining technique also produced a
      false-negative result. The PCR may have produced false-positive results for one
      cell culture. Ambiguous results were obtained with the remaining two cell
      cultures. Furthermore, the presence of contaminating bacteria interfered with the
      interpretation of the DNA staining results for 16 cell cultures. For the same
      reason the hybridization signals of nine cell cultures could not be interpreted.
      Our results demonstrate the drawbacks of each of the detection methods and the
      suitability of the PCR for the detection of mycoplasmas in cell cultures.

PMID- 7509585
TI  - Identification of Erwinia stewartii by a ligase chain reaction assay.
AB  - A PCR-coupled ligase chain reaction (LCR) assay was developed to distinguish the
      plant pathogenic bacterium Erwinia stewartii from other erwiniae. This new
      technique allows discrimination to the species level on the basis of a single
      base-pair difference in the 16S rRNA gene which is unique to E. stewartii.
      Portions of the 16S rRNA genes of E. stewartii and the closely related Erwinia
      herbicola were sequenced. From comparison of the two 16S rRNA gene regions, two
      primer pairs were constructed such that only E. stewartii DNA gave a product in
      the LCR assay. The ligated product was separated from the radioactively labelled
      primers by denaturing polyacrylamide gel electrophoresis and visualized by
      autoradiography. Twenty-four different Erwinia species and strains were tested by
      PCR-coupled LCR to verify the specificity of the assay, and only E. stewartii
      strains gave a positive reaction. In addition, infected and healthy plant
      material was also assayed. E. stewartii was detected in infected plant material,
      even when large populations of epiphytic bacteria were present. No enrichment was
      necessary for detection of the pathogen in corn leaves. This assay has potential
      as a diagnostic technique for the detection of E. stewartii in infected plant and
      vector material.

PMID- 7509586
TI  - Identification and characterization of a new plasmid carrying genes for
      degradation of 2,4-dichlorophenoxyacetate from Pseudomonas cepacia CSV90.
AB  - Pseudomonas cepacia CSV90 is able to utilize 2,4-dichlorophenoxyacetate (2,4-D)
      and 2-methyl-4-chlorophenoxyacetate as sole sources of carbon and energy. Mutants
      of the strain CSV90 which had lost this ability appeared spontaneously on a
      nonselective medium. The wild-type strain harbored a 90-kb plasmid, pMAB1,
      whereas 2,4-D-negative mutants either lost the plasmid or had a 70-kb plasmid,
      pMAB2. The plasmid pMAB2 was found to have undergone a deletion of a 20-kb
      fragment of pMAB1. The plasmid-free mutants regained the ability to degrade 2,4-D
      after introduction of purified pMAB1 by electroporation. Cloning in Escherichia
      coli of a 10-kb BamHI fragment from pMAB1, the region absent in pMAB2, resulted
      in the expression of the gene tfdC encoding 3,5-dichlorocatechol 1,2-dioxygenase.
      After subcloning, the tfdC gene was located in a 1.6-kb HindIII fragment. The
      nucleotide sequence of the tfdC gene and the restriction map of its contiguous
      region are identical to those of the well-characterized 2,4-D-degradative plasmid
      pJP4 of Alcaligenes eutrophus, whereas the overall restriction maps of the two
      plasmids are different. The N-terminal 44-amino-acid sequence of the enzyme
      purified from the strain CSV90 confirmed the reading frame in the DNA sequence
      for tfdC and indicated that the initiation codon GUG is read as methionine
      instead of valine.

PMID- 7509589
TI  - Aging and proteolysis of oxidized proteins.
AB  - The main objective of this study was to investigate the possible cause(s) of the
      age-related augmentation of oxidatively damaged proteins in animal tissues. The
      hypothesis that activity of alkaline proteases, involved in the proteolysis of
      oxidized proteins, declines during aging was tested in the adult male housefly
      and further explored in the rat. Alkaline protease activity was measured
      fluorometrically by the release of trichloroacetic acid-soluble fluorescamine
      reactive material from X ray-oxidized bovine serum albumin (BSA). Alkaline
      protease activity in the housefly was linearly related to the number of protein
      carbonyl groups. Possible involvement of serine or serine and thiol proteases was
      deduced from a 70% proteolytic inhibition by aprotinin and a 50% inhibition by
      leupeptin. Protease activity of houseflies for oxidized or native BSA did not
      alter with age. In contrast, a varied age-related pattern of protease activity
      was observed in the tissues of the rat. A comparison of 3-, 13-, and 23-month-old
      Sprague-Dawley rats indicated no age-related decline in alkaline protease
      activity in the brain, a 50% decline in the liver, and a 20% decline in the heart
      during 13 to 22 months. Results of this study suggest that in some species or
      tissues an age-related increase in the oxidized protein content is primarily due
      to a corresponding increase in the rate of protein oxidation, while in some other
      tissues a decline in proteolysis may be a contributory factor.

PMID- 7509587
TI  - Transcriptional enhancement of the Listeria monocytogenes PCR and simple
      immunoenzymatic assay of the product using anti-RNA:DNA antibodies.
AB  - A method was developed to enhance the sensitivity of a Listeria monocytogenes PCR
      detection system by in vitro transcription of amplicons incorporating
      bacteriophage T7 RNA polymerase promoter sequences in one of the priming
      oligonucleotides. The resulting transcript can be detected by hybridization with
      a DNA probe immobilized in the wells of a microtiter plate, followed by
      immunoenzymatic assay of the RNA-DNA hybrids with an anti-RNA-DNA hybrid
      antibody. This highly sensitive method was reactive in the assay of various L.
      monocytogenes isolates but not with other Listeria or non-Listeria species.

PMID- 7509590
TI  - Probing the affinity of polyanions for acidic fibroblast growth factor by
      unfolding kinetics.
AB  - The relationship between ligand-protein affinity and the extent of protein
      stabilization induced by such interactions has been investigated using the
      binding of polyanions to acidic fibroblast growth factor (aFGF) as a model
      system. It was found that the experimentally observed unfolding rate constant of
      aFGF consists of two components: one equal to the unfolding rate constant of the
      aFGF-ligand complex and the other the product of the unfolding rate constant of
      free aFGF, the aFGF-ligand dissociation constant (Kd), and the reciprocal of the
      molar ligand concentration. This reflects the presence of two possible unfolding
      pathways: at high ligand excess dissociation is suppressed and slow unfolding of
      the aFGF-ligand complex itself prevails. When lower concentrations of ligand
      allows equilibrium-driven appearance of free aFGF, a more rapid unfolding of
      dissociated protein predominates. Existence of a steady state of dissociated aFGF
      undergoing unfolding was demonstrated by computer simulation of the elementary
      events, using experimentally determined rate constants. The potential
      applications of such simulations are outlined. An equation allowing estimation of
      dissociation constants from equilibrium denaturation curves obtained in the
      presence of a varying amount of ligand is also proposed. In addition,
      determination of initial unfolding rates in the presence of excess protein
      permits the the stoichiometry of the interaction to be determined.

PMID- 7509588
TI  - A bioassay based on recombinant DNA technology for determining selenium
      concentration.
AB  - The trace element selenium has recently attracted attention, particularly because
      (i) selenocysteine is involved in the active site of various prokaryotic and
      eukaryotic enzymes, some of which have a role in human health; (ii)
      selenocysteine incorporation into these proteins is coded by UGA codons; and
      (iii) as a result, selenocysteine is now considered to be the 21st amino acid in
      an expanded genetic code. Here, we built recombinant DNA constructs in which
      expression of the lac'Z gene is driven in Escherichia coli by UGA-directed
      selenocysteine incorporation. In this system, levels of beta-galactosidase
      activity are proportionally and specifically related to the presence and
      concentrations of several specific simple selenium derivatives. The system can
      thus be used as a sensitive bioassay for their determination. This bioassay is
      one of a few using recombinant DNA technology to provide a reporter for simple
      detection of a chemical trace element.

PMID- 7509591
TI  - Fc gamma RI and Fc gamma RIII on polymorphonuclear leucocytes in cord blood.
AB  - Fc gamma RI and Fc gamma RIII expression on polymorphonuclear leucocytes in cord
      blood from seven normal infants was investigated by flow cytometry. Fc gamma R
      expression on fresh polymorphonuclear leucocytes in whole blood samples and in
      blood samples incubated with or without interferon gamma (IFN-gamma) for 48 hours
      was also studied. The percentage of Fc gamma RIII positive polymorphonuclear
      leucocytes in cord blood (73.3%) was significantly lower than that in adult
      controls (95.9%). The mean fluorescence intensity of Fc gamma RIII was
      significantly increased on cord polymorphonuclear leucocytes by the incubation
      with IFN-gamma. Fresh cord polymorphonuclear leucocytes expressed only a small
      amount of Fc gamma RI as adult polymorphonuclear leucocytes. The percentage of Fc
      gamma RI positive polymorphonuclear leucocytes induced with IFN-gamma was
      significantly higher in cord blood (62.3%) than in adult controls (30.3%). It is
      possible that decreased expression of Fc gamma RIII is a factor in the
      susceptibility of newborns to infection. High expression of Fc gamma RI
      stimulated with IFN-gamma in neonates could have a compensatory role against
      decreased immunological function.

PMID- 7509592
TI  - Evaluation of daily dietary intake of dichloro-diphenyl-trichloroethane (DDT) and
      benzene hexachloride (BHC) in India.
AB  - Duplicate samples of the diet of vegetarian adults were analyzed to estimate the
      residues of dichloro-diphenyl-trichloroethane (DDT) and benzene hexachloride
      (BHC). The total food consumed by an adult per day was collected and categorized
      as fatty food, non-fatty food, water, and beverages. Fatty food was the main
      source of these chlorinated insecticides, and it contributed almost 50% of the
      total dietary intake. The average total DDT and BHC consumed by an adult were
      19.24 micrograms/d and 77.15 micrograms/d, respectively. Blood DDT and BHC levels
      reflected intake (r = 0.685 for DDT; r = 0.515 for BHC).

PMID- 7509593
TI  - Chronic hepatitis C. Advances in diagnostic testing and therapy.
AB  - The methods for diagnosing hepatitis C virus infection have been evolving since
      the first-generation enzyme-linked immunosorbent assay antibody test was devised
      in 1989. In addition to assaying for serum antibodies against viral proteins,
      serum and liver tissue can be tested for viral RNA, evidence of ongoing viral
      replication. The improving ability to diagnose hepatitis C has furthered the
      understanding of the natural history of this infection. Acute hepatitis C results
      in chronic elevations of serum transaminase levels following nearly one half of
      cases. Cirrhosis complicates approximately 20% of chronic infections. Long
      standing chronic hepatitis C may play a role in the pathogenesis of
      hepatocellular carcinoma. Sustained normalization of serum transaminase levels,
      often accompanied by a decrease in or disappearance of viral RNA, occurs in
      approximately 25% of patients with chronic hepatitis C who are treated with a 6
      month course of recombinant interferon alfa. This treatment can occasionally be
      complicated by hematologic, endocrinologic, and psychiatric adverse effects but
      is usually fairly well tolerated. Whether interferon therapy will diminish the
      risk of cirrhosis or carcinoma is not yet known. This article reviews the
      diagnosis of chronic hepatitis C infection as well as the mechanisms of action,
      efficacy, and adverse effects associated with interferon alfa therapy.

PMID- 7509594
TI  - Disruptive influence of norepinephrine depletion on sensory preconditioning, but
      not first-order conditioning, in preweanling rats.
AB  - Learning and memory processes are known to be influenced by the action of
      norepinephrine (NE). The present study evaluated the influence of neonatal
      administration of the NE neurotoxin DSP4 on sensory preconditioning (SPC) in 16-
      and 28-day-old rats. Rats were subcutaneously administered 50 mg/kg DSP4 or
      saline within 24 h after birth and tested at 16 or 28 days in two experiments.
      The results from Experiment 1 indicated that nondepleted 16-day-old rats
      exhibited strong SPC, whereas this conditioning was disrupted by neonatal
      administration of DSP4. No SPC was seen in either neonatal treatment group at 28
      days of age, confirming previous reports of an ontogenetic decline in SPC. In
      Experiment 2, no effects of DSP4 were observed on first-order conditioning at
      either age. The brains of representative subjects were separated into forebrain,
      cerebellum, and brain stem samples and were analyzed to determine the extent of
      NE depletion. This analysis showed that DSP4 produced a marked reduction in NE
      concentration in the forebrain, but not in the cerebellum or brain stem. The
      results of this study suggest a role for forebrain NE in SPC in preweanling rats.
      This modulatory noradrenergic influence appears to be exerted on the formation of
      associations between two relatively neutral stimuli during the preexposure phase,
      given the absence of an effect of DSP4 on primary conditioning.

PMID- 7509595
TI  - Identification of differentially expressed members of tobacco homeobox families
      by differential PCR.
AB  - As a first step to investigate the functions of homeobox genes in tobacco genetic
      tumorigenesis, we have used polymerase chain reaction to identify Hot (Homeobox
      in tobacco) genes that are expressed in tobacco genetic tumors. Five Hot genes
      that are actively expressed in tobacco genetic tumors are identified.
      Particularly, Hot1 is profoundly abundant in tumorous tissues, suggesting that it
      acts as a positive regulator of cell growth and differentiation during genetic
      tumorigenesis.

PMID- 7509596
TI  - Gene structure, polymorphism and mapping of the human endothelial nitric oxide
      synthase gene.
AB  - Endothelium-derived relaxing factor (EDRF)/nitric oxide (NO) is synthesized from
      L-Arginine by the endothelial, constitutive, NO synthase. No facilitate genetic
      studies, we have cloned the human endothelial NO synthase gene and determined its
      structure. The gene is composed of 26 exons, ranging from 68 to 579 bp and spans
      22 kb. We determined the transcription start point using human lung mRNA. No TATA
      box was found at the expected distance from the transcription start point and
      several consensus sequences for transcription factors, including a shear-stress
      responsive element were identified in the 5'-flanking region. A highly
      polymorphic (CA) repeat within intron 13 was studied, allowing the precise
      genetic mapping of the gene to chromosome 7, within a 4 cM interval delimited by
      genethon markers AFM199Zd4 and AFM074Xg5.

PMID- 7509597
TI  - Cloning of cDNAs for fructose 6-phosphate 2-kinase/fructose 2,6-bisphosphatase
      from frog skeletal muscle and liver, and their expression in skeletal muscle.
AB  - Frog (Rana catesbeiana) skeletal muscle (M-type) and liver (L-type) cDNAs of
      fructose 6-phosphate 2-kinase/fructose 2,6-bisphosphatase were isolated from
      lambda gt10 phage cDNA library. The full-length L-type cDNA (1829 bp) encodes a
      469 amino acids subunit (M(r) 54,800), while the M-type cDNA (1792 bp) encodes
      455 amino acids (M(r) 52,901). The amino acid sequence of the M-type isozyme is
      identical to that of the L-type isozyme except for the N-terminus. The N-terminal
      30 amino acids of the L-type isozyme are replaced by an unique sequence of 16
      amino acids in the M-type isozyme. Both L- and M-type cDNAs were detected also in
      a lambda gt10 phage library of skeletal muscle. Relative amount of the M- and L
      type mRNAs is skeletal muscle was determined by the reverse transcription
      polymerase chain reaction method. The M/L mRNA ratio in frog skeletal muscle
      shows seasonal variations, being 0.56/1 in early summer and 5.3/1 in winter.
      These results suggest that there is a seasonal change in the isozyme composition
      and that the glycolysis in frog skeletal muscle may be regulated by type of the
      isozyme synthesized.

PMID- 7509598
TI  - Mutagenesis of the nuclear localization sequence in EGF-1 alters protein
      stability but not mitogenic activity.
AB  - Fibroblast growth factor (FGF)-1 is able to translocate to the nucleus as an
      exogenous protein and a deletion of the nuclear localization sequence near the
      NH2-terminus of FGF-1 (FGF-1(28-154)) yields a recombinant polypeptide with
      impaired mitogenic activity. To study the significance within this region
      (NYKKPK), five FGF-1 point mutations were constructed and their recombinant
      protein forms analyzed. Interestingly, none of the mutant protein products showed
      a significant reduction in mitogenic activity when compared to wild-type protein.
      Because these data suggested possible structural instability within the FGF-1(28
      154) deletion mutant, protein structure was examined by fluorescence
      spectroscopy. Indeed, the FGF-1 point mutations which had similar mitogenic
      activity to wild-type FGF-1 displayed similar thermal fluorescence spectroscopy
      patterns as wild-type protein, but FGF-1(28-154) exhibited altered fluorometric
      profiles. However, the mitogenic activity and structural stability of FGF-1(28
      154) was dependent upon the method used to purify the recombinant, whereas
      purification methods did not effect FGF-1(21-154) mitogenic activity. These
      studies suggest that the reduced mitogenic activity observed in preparations of
      the FGF-1(28-154) deletion mutant may be the result of structural instability and
      fluorescence spectroscopy cannot be used to predict FGF-1 stability.

PMID- 7509599
TI  - Insulin-like growth factors (IGFs) and IGF binding protein-3 display disulfide
      isomerase activity.
AB  - Insulin-like growth factors (IGF-I and -II) bind with high affinity to IGF
      binding proteins (IGFBPs). IGFBP-3 contains vicinal cysteines in sequence which
      is similar to the active sites in thioredoxin and protein disulfide isomerase. We
      tested if, in analogy with these redox enzymes, IGFBP-3 could catalyze the
      isomerization of intramolecular disulfide bridges in protein substrates. IGFBP-3
      (30 microM) was able to reactivate reduced ribonuclease at a rate of 38% of that
      of thioredoxin. Also recombinant IGF-I induced the regeneration of ribonuclease
      activity. Thiol redox reactions are known to play a role in regulating
      conformational changes in the insulin receptor and possibly also in the IGF-I
      receptor. Therefore, the intrinsic isomerase activities of IGF-I may be important
      in the activation of its receptor. The observed effects of IGFBP-3 may help to
      elucidate the mechanism by which this binding protein can modulate the actions of
      IGF-I.

PMID- 7509600
TI  - Antisense RNA to the first N-glycosylation gene, ALG7, inhibits protein N
      glycosylation and secretion by Xenopus oocytes.
AB  - N-Glycosylation has been shown to affect the rate of glycoprotein transport
      through the secretory pathway. In order to identify the critical components in
      the N-glycosylation pathway that directly influence protein secretion, we have
      studied the effects of downregulation of the first gene in the dolichol pathway,
      ALG7, on the synthesis, glycosylation and secretion of native and heterologous
      proteins by Xenopus laevis oocytes. Our strategy involved the use of ALG7
      antisense RNA (asRNA) to lower the effective abundance of the ALG7 protein in
      oocytes. The results showed that there was an inverse dose-response relationship
      between ALG7 asRNA and the amount of glycosylated and secreted proteins. These
      effects were also observed for heterologously expressed rat parotid amylase.
      Since ALG7 asRNA did not inhibit overall protein synthesis, we conclude that
      downregulation of ALG7 expression directly lowered protein export.

PMID- 7509601
TI  - Proliferative effect of parathyroid hormone-related protein on the hypercalcemic
      Walker 256 carcinoma cell line.
AB  - The rat Walker 256 carcinoma is an animal model for humoral hypercalcemia of
      malignancy. This tumor produces and secretes parathyroid hormone (PTH)-related
      protein (PTHrP), a likely mediator for this syndrome. In this study, we
      investigated the effect of PTHrP on Walker 256 tumor cell proliferation. We found
      that [Tyr36]human (h)PTHrP (1-36)NH2 and hPTHrP (1-86), unlike hPTHrP (38-64)NH2,
      stimulate DNA synthesis dose-dependently in these cells. A similar mitogenic
      effect was also observed with bovine (b)PTH (1-34) or (Nle8.18, Tyr34)bPTH (3
      34)NH2. Moreover, addition of anti-hPTHrP (1-34) neutralizing antibodies
      decreased tumor cell growth. Conversely, 10(-4)M dibutyryl cAMP or Sp-cDBIMPS (a
      cAMP analogue) inhibited DNA synthesis in these cells, being incompetent at lower
      doses. PTHrP or PTH failed to stimulate cAMP production, but they induced a
      cytosolic calcium transient increase in these cells. These findings support an
      autocrine role of PTHrP in the regulation of this tumor growth.

PMID- 7509602
TI  - Inducible nitric oxide synthase is increased in murine lung epithelial cells by
      cytokine stimulation.
AB  - Nitric oxide (NO) is detectable in exhaled air. To elucidate whether airway
      epithelial cells could be a source of NO, we investigated the expression of
      inducible nitric oxide synthase (iNOS) by the murine lung epithelial cell line,
      LA-4, in response to cytokine stimulation and the ability of corticosteroids to
      modulate this effect. Stimulation with cytomix, a combination of interleukin-1
      beta, tumor necrosis factor-alpha, and interferon-gamma, elevated nitrite levels
      by 873% in the culture supernatants and enhanced the conversion of arginine to
      citrulline by 273% at 24 h. An increased number of cells stained for iNOS and an
      increase in iNOS mRNA was also observed. Dexamethasone decreased the cytokine
      induced increase in nitrite levels, NOS activity, iNOS immunoreactivity, and mRNA
      but did not change the half life of iNOS mRNA. These results show that lung
      epithelial cells can release NO, a process which can be inhibited by
      dexamethasone.

PMID- 7509603
TI  - Cytosol treated with GTP gamma S disintegrates lysosomes in vitro.
AB  - Cytosol that was treated with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)
      disintegrated lysosomes in a dose dependent manner, as detected by the release of
      preloaded fluorescein isothiocyanate-dextran from lysosomes. This phenomenon is a
      consequence of the two successive steps of incubation, (i) the treatment of
      cytosol with GTP gamma S, and (ii) the disintegration of lysosomes by the treated
      cytosol. The first step was specific for GTP gamma S and the effect of GTP gamma
      S was suppressed by GTP or GDP. The second step required ATP but it was not
      affected by bafilomycin A1. GTP gamma S treatment of lysosomes themselves did not
      induce their lysis. The lytic "factor(s)" produced in GTP gamma S-treated cytosol
      consisted of high molecular weight protein(s).

PMID- 7509604
TI  - [Search for T-epitopes of the hepatitis A virus using synthetic peptides].
AB  - Computer search for probable T-epitopes of the hepatitis A virus capsid proteins
      was performed using developed integrated set of programmes. The following
      peptides were chosen and synthesised by solid phase technique: 75-92 VP1, 115-139
      VP1, 209-221 VP1, 69-99 VP2, 80-99 VP2, 45-57 VP3, 137-150 VP3 and 1-23 VP4.
      Peptides 1-17 VP1, 10-33 VP1, 11-25 VP1, 75-85 VP1 and 276-298 VP1 previously
      examined as probable B-epitopes were used as well. All the peptides were tested
      for their ability to stimulate proliferation of lymph node T-cells primed with
      synthetic peptides. Almost all the predicted T-epitopes did affected the T-cell
      proliferation. 10-33 VP1 and 276-298 VP1 stimulated lymph node proliferation of
      all tested mouse strains. 107-126 VP1 and 115-126 VP1 did not influence
      proliferation of lymphocytes of mice primed with these peptides but stimulated
      proliferation of T-cells of F1 (CBA x C57Bl6) mice primed with 115-139 VP1.

PMID- 7509605
TI  - [Reduction of the post-transfusion hepatitis C risk in patients undergoing bone
      marrow allograft].
AB  - Post-transfusion hepatitis C incidence was studied in a series of patients with
      bone marrow allograft. The risk of HCV seroconversion was evaluated according to
      the date of grafting and the screening tests carried out in blood donors at this
      time. Anti-HCV antibodies were screened using Elisa tests of 2d generation and
      confirmed by Riba tests of 2d generation. Results were analysed. Out of 181
      allografted patients from January 1987 to December 1991, 120 patients found anti
      HCV negative prior to grafting, with at least six month post-transfusion follow
      up were considered as evaluable in terms of HCV seroconversion. All these
      patients had received leucodepleted blood products and the most of them platelet
      unit concentrates. Prior to implementation of screening tests for non-A, non-B
      hepatitis, 14% of patients had seroconverted (0.44% per transfused product);
      after introduction of the screening for indirect markers (ALAT) and for
      antibodies directed against the antigen of hepatitis B virus core (anti-HBc), the
      seroconversion incidence was 4% (0.26% per product). At the present time, since
      the implementation of anti-HCV screening tests, the risk has reached 1.6% (0.03%
      per transfused product). 6 patients out of 7 having seroconverted have been
      developing chronic hepatitis.

PMID- 7509606
TI  - Low and high dose bromocriptine have different effects on striatal dopamine
      release: an in vivo study.
AB  - We wished to determine if low and high doses of bromocriptine produce distinct
      patterns of dopamine release and metabolism. Accordingly, we administered
      bromocriptine (0, 2.5, 5, and 10 mg/kg, IP) to rats and monitored extracellular
      concentrations of dopamine and dopamine metabolites in the corpus striatum with
      the technique of cerebral microdialysis. Extracellular dopamine levels increased
      following administration of 2.5 and 5 mg/kg bromocriptine. In contrast, dopamine
      levels decreased following 10 mg/kg bromocriptine. Dopamine metabolite levels
      decreased 45 minutes following all doses of bromocriptine. Bromocriptine
      administration had no effect on the levels of 5HIAA, the major serotonin
      metabolite. These findings with high dose bromocriptine fit the predicted profile
      of a dopamine D2 receptor agonist. The delayed decrease in dopamine metabolites
      at all bromocriptine doses is consistent with the known dopamine synthesis
      inhibiting action of bromocriptine. In contrast, the increased dopamine release
      observed following low and medium doses of bromocriptine is not readily
      explainable by current theories of bromocriptine action which predict decreased
      dopamine release and therefore decreased striatal extracellular dopamine levels
      with both high and low-doses of bromocriptine. Our findings indicate that
      bromocriptine has a complex pharmacological action that extends beyond simple
      agonism at dopamine D2 receptors.

PMID- 7509607
TI  - Lack of ACTH/cortisol and GH responses to intravenously-infused substance P in
      Parkinson's disease.
AB  - In order to test possible changes in the stimulating effect of intravenously
      infused substance P (SP) on ACTH/cortisol and GH secretion in Parkinson's
      disease, 10 male parkinsonian patients and 10 age-matched normal controls were
      infused intravenously for 60 min with SP (1.0 or 1.5 pmol/kg-1/min-1 SP) or
      normal saline. The circulating levels of ACTH, cortisol and GH were measured
      during and for 20 min after SP or saline infusion. No untoward side effects or
      changes in blood pressure were observed during SP infusion in any subjects. In
      basal conditions and during saline infusion, plasma ACTH and cortisol levels were
      similar in normal and parkinsonian patients. During SP infusions, ACTH/cortisol
      concentrations in normal controls rose significantly vs baseline and saline test
      in a dose-dependent fashion. In contrast, at both SP infused amounts,
      parkinsonian patients showed ACTH/cortisol levels similar to those observed in
      the saline test. All subjects showed similar basal concentrations of GH. GH
      levels rose significantly in the normal controls when the higher dose of SP was
      infused, but they were not modified by the infusion of the lower dose of SP or
      saline. At both tested amounts of SP and during saline infusion, GH levels
      remained unchanged in the parkinsonian subjects. In agreement with previous
      observations in the literature showing SP abnormalities in the parkinsonian
      brain, these data fail to show significant effects of plasma SP on the
      ACTH/cortisol and GH secretory systems in Parkinson's disease.

PMID- 7509608
TI  - Excitotoxic lesions of basal forebrain cholinergic neurons: effects on learning,
      memory and attention.
AB  - A substantial body of literature has suggested that the memory and learning
      deficits associated with Alzheimer's disease are attributable to degeneration of
      the cholinergic magnocellular neurons of the nucleus basalis of Meynert (nbM).
      Subsequently, lesion-induced damage to the cholinergic projections from the nbM
      to the neocortex has been utilized extensively as an animal model of dementia.
      Ibotenic acid lesions of the basal forebrain have been found, for example, to
      produce deficits in a wide variety of tasks involving learning and memory.
      However, recently, with the availability of more potent cholinergic excitotoxins
      such as AMPA, it has become apparent that nbM lesions do not provide a simple
      animal model of the cognitive deficits in ageing and Alzheimer's disease. Further
      analysis suggests that many of the learning and memory impairments traditionally
      attributed to the cholinergic corticopetal system are due not to destruction of
      cholinergic neurons in the nbM, but instead result from the disruption of cortico
      striatal outputs passing through the dorsal and ventral globus pallidus.
      Furthermore, experiments utilizing quisqualic acid and AMPA have revealed that
      the most convincing deficit observed as a result of such lesions is in visual
      attention. This role for the basal forebrain-cortical cholinergic system in
      attentional function is further supported by results obtained from complementary
      pharmacological studies. This does not exclude a role for acetylcholine in
      learning and memory processes. Rather, such cognitive processes appear to depend
      not upon the integrity of the nbM itself, but upon more rostral elements of the
      cholinergic basal forebrain system.

PMID- 7509610
TI  - Lung epithelial lining fluid T cell subsets defined by distinct patterns of beta
      7 and beta 1 integrin expression.
AB  - Integrins are heterodimeric cell-surface glycoproteins that mediate cell-cell and
      cell-matrix adhesion. We previously identified cDNA encoding a novel integrin
      beta subunit, beta 7, from bronchoalveolar lavage fluid (BALF) leukocytes. The
      beta 7 subunit protein is now known to associate with at least two integrin alpha
      subunits on lymphocytes. One beta 7 integrin, alpha 4 beta 7, mediates lymphocyte
      adhesion to endothelium and to fibronectin. The other known beta 7 integrin,
      alpha E beta 7, has recently been shown to mediate lymphocyte-epithelial cell
      adhesion in vitro. We used flow microfluorometry to analyze the expression of
      alpha 4 beta 7, alpha E beta 7, and other integrins on blood T cells and
      epithelial lining fluid T cells obtained from five healthy adult volunteers by
      bronchoalveolar lavage. alpha 4 beta 7 was the predominant beta 7 integrin on
      blood T cells, whereas alpha E beta 7 was predominant on BALF T cells. BALF T
      cells could be divided into alpha E beta 7- and alpha E beta 7+ subsets. Between
      29 and 61% (mean 42%) of CD3+ T cells were alpha E beta 7+ alpha E beta 7 was
      more likely to be present on CD8+ T cells (mean 69% alpha E beta 7+) than on CD4+
      T cells (mean 29% alpha E beta 7+). The alpha E beta 7- and alpha E beta 7+ BALF
      T cell subsets were also found to differ in their expression of other
      integrins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509609
TI  - Functional interactions of galanin and acetylcholine: relevance to memory and
      Alzheimer's disease.
AB  - Galanin, a 29-amino acid neuropeptide, is the only peptide known to coexist with
      acetylcholine in the basal forebrain neurons which degenerate early in the
      progression of Alzheimer's disease. Biochemical and neurophysiological studies
      demonstrated inhibitory actions of galanin on cholinergic functions. Behavioral
      investigations found that intracerebrally administered galanin produces deficits
      on spatial learning and memory tasks in rats. Taken together, the current
      literature suggests that galanin acts as an inhibitory modulator of acetylcholine
      in this coexistence. Particularly in the case of Alzheimer's disease, where
      cholinergic activity is severely compromised, the negative actions of galanin may
      be particularly deleterious. Recently developed galanin antagonists may provide a
      novel therapeutic approach toward enhancing memory processes in Alzheimer's
      disease, by removing the putative inhibitory actions of endogenous galanin on the
      remaining basal forebrain cholinergic neurons.

PMID- 7509611
TI  - Mesothelial cell proliferation: a nonspecific response to lung injury associated
      with fibrosis.
AB  - An early proliferative response of mesothelial and subpleural cells has been
      reported in animals after inhalation or intratracheal (I.T.) instillation to the
      lung of long asbestos fibers, which also induce pulmonary fibrosis. To determine
      whether this cell proliferation is directly related to asbestos exposure or is a
      nonspecific response to injury, we examined [3H]thymidine (3HT) uptake by cells
      at the pleura after exposing mice to 5 days of hyperoxia, to intravenous (I.V.)
      (3 mg) or I.T. (0.15 mg) bleomycin, to I.T. (1 mg) silica, and to I.T. (0.1 mg)
      crocidolite asbestos of mixed length. All exposures induced acute lung injury, as
      shown by high levels of protein in lavage fluid. After hyperoxia, the percentage
      of total lung cells labeled by 3HT in autoradiographs was high for only a few
      days, as repair took place with no increase in fibroblast growth and no
      subsequent development of fibrosis. Particle or bleomycin exposure induced a
      prolonged increase in 3HT uptake with enhanced fibroblast labeling over a 4- to 6
      wk period. In each case, labeled subpleural cells, mainly fibroblasts, increased
      up to 10-fold in the first 2 to 4 wk. At the same time, 3HT uptake by mesothelial
      cells ranged from 1.4 to 3% compared with almost zero in controls and in oxygen
      exposed mice after a few days upon return to air. These results indicate that
      mesothelial and subpleural cell proliferation occurs after various types of
      injury to the lung. The close temporal association between 3HT uptake by
      mesothelial cells and fibroblasts during the reparative phase suggests that
      mesothelial cells may respond to the same cytokines that trigger interstitial
      fibrosis.

PMID- 7509613
TI  - Issues of symptom control in patients with advanced cancer.

PMID- 7509612
TI  - Endothelin-1 promotes mitogenesis in airway smooth muscle cells.
AB  - Endothelin exists as three isoforms (ET-1, ET-2, and ET-3) and exhibits
      vasoconstricting, bronchoconstricting, and growth-promoting properties in
      vascular smooth muscle. In the airways, ET-1 immunoreactivity and mRNA have been
      detected and localized to the epithelium, smooth muscle, and endothelium in
      different species, including humans. It has been suggested that ET-1 may have a
      role in the airway smooth muscle hyperplasia and hypertrophy seen in patients
      with bronchial asthma. We studied ovine airway smooth muscle cells (SMC) in vitro
      and showed saturable binding of [125I]ET-1 with a dissociation constant (Kd) of
      0.4 nM and high affinity binding sites (Bmax) for ET-1 (104 fmol/10(6) cells).
      This binding was functional as ET-1 promoted mitogenesis of these muscle cells as
      measured by increased cell number in the absence of serum. Twenty-four hours
      after exposing the cells to graded doses of ET-1 from 1 pM to 1 microM, cell
      number increased significantly over control in a dose-dependent manner. ET-1 also
      enhanced the transient expression of c-fos mRNA by 2.5-fold over control, with
      maximal expression occurring at 30 min. These observations provide evidence that:
      (1) airway SMC possess high affinity binding sites for ET-1, and (2) ET-1 is
      mitogenic for airway SMC as determined by increased cell number and amplification
      of c-fos mRNA expression. ET-1 may have a fundamental role in influencing the
      growth of smooth muscle in the airways.

PMID- 7509614
TI  - [The role of iloprost in the treatment of critical ischemia of the limbs].
AB  - Iloprost is a synthetic stable analogue of prostacyclin (PGI2), which shares its
      antiaggregating and vasodilating properties. Iloprost has been administered by
      i.v. route to patients with critical limb ischaemia (CLI) of different origin
      (maximal dosage: 2 ng/kg/min 6 hours/day infusion for 14-28 days). In patients
      with claudicatio intermittens (Fontaine stage II) iloprost improved the time to
      claudication and the maximal walking distance on treadmill, with an effect still
      lasting 60 days after suspension. This benefit was not related to a significant
      improvement in blood flow. Five multicentric, perspective, randomized versus
      placebo studies in patients with more severe CLI (Fontaine stage III-IV)
      susceptible to surgical treatment, showed that iloprost was able to reduce pain
      and ulcer dimensions. Furthermore, tha amputation rate of the ischemic limb was
      significantly lower in patients treated with iloprost during a 6 month follow-up
      (p < 0.01). Iloprost was also more effective than aspirin in causing pain relief
      and ulcer healing in patients with thromboangiitis obliterans and more effective
      than nifedipine in reducing frequency, intensity and duration of ischemic
      episodes in patients with Raynaud's phenomenon. Minor side effects of iloprost
      administration are represented by facial flushing, tachycardia, headache, nausea,
      vomiting, abdominal cramping, diarrhoea, whose frequency ranges from 16% to 70%;
      major collateral effects, occurring in less than 5% of patients, are above all
      represented by severe hypotension and angina pectoris. Clinical data indicate
      therefore that iloprost treatment can allow to improve the clinical conditions
      and the prognosis in patients with critical ischemia of the limbs, not candidate
      to surgical revascularization, by causing a relief of pain, a reduction in ulcer
      dimensions and deferring amputation.

PMID- 7509615
TI  - [The role of iloprost in vascular surgery].
AB  - Use of prostanoids in vascular surgery is valuable in various conditions: intra
      and postoperatively, during limb salvage procedures, they are useful to lower
      peripheral resistances, and in patients with limited gangrene, when surgery is
      not feasible, they improve limb blood flow. After some years of subjective
      clinical evaluation, multicentric randomized clinical trials started; the aim was
      to quantify the real benefit derived from the use of prostanoids to the evolution
      of limb ischemia and to the improvement of results of surgical revascularization.
      We have not yet definitive results; preliminary data show a better immediate
      patency rate of femoro-distal bypass grafts and a critical reduction in long term
      limb amputations.

PMID- 7509616
TI  - Treatment of systemic sclerosis.
AB  - Although there have been no major breakthroughs in scleroderma therapy, new
      treatments have been tested in patients with systemic sclerosis, including both
      interferon alfa and interferon gamma. These biologic agents can reduce collagen
      synthesis, which is a rational target for scleroderma therapy. Debate about the
      use of photopheresis continues, and it was suggested in a recent editorial that
      photopheresis is no better than D-penicillamine in the treatment of scleroderma
      and is more expensive. Cyclosporine appears to have frequent renal toxicity when
      used to treat scleroderma. Outcome measurements have been concentrated on in
      scleroderma trials. Several types of scleroderma classifications were compared,
      and the classification of diffuse and limited scleroderma was strongly related to
      disease severity. Skin score was systematically compared with mapping the surface
      area of involved skin, and the skin score was found to be more reliable. A
      possible prognostic indicator in scleroderma is high-resolution pulmonary
      computed tomography, which is sensitive in early detection of scleroderma
      associated interstitial lung disease. Classification of Raynaud's phenomenon into
      primary and secondary forms has been proposed, and further testing of the
      criteria and long-term follow-up is necessary to validate this classification.
      Over the past year, treatment of vasospasm with prostacyclin analogues has been
      efficacious with iloprost but not with low-dose oral cicaprost. Tissue
      plasminogen activator is not beneficial in the treatment of Raynaud's phenomenon.
      A report of radical microarteriolysis for the treatment of refractory Raynaud's
      phenomenon seems promising, warranting further investigation.

PMID- 7509617
TI  - Genetic polymorphism of inter-alpha-trypsin inhibitor (ITI) in the Basque Country
      (northern Spain).
AB  - The genetic polymorphism of inter-alpha-trypsin inhibitor (ITI) was analyzed in 2
      samples of 554 residents and 303 autochthonous healthy unrelated individuals from
      the Basque Country (northern Spain), by isoelectric focusing on miniaturized
      polyacrylamide gels followed by immunoblotting. The allele frequencies were ITI*1
      = 0.586, ITI*2 = 0.402 and ITI*3 = 0.012 in residents and ITI*1 = 0.548, ITI*2 =
      0.449 and ITI*3 = 0.003 in the autochthonous population. These allele frequencies
      were compared with those reported in other European populations.

PMID- 7509618
TI  - Microthrombi formation after severe head trauma.
AB  - This study was undertaken to look for trauma-related fibrinous microthrombi in
      traumatized human brains. Fifty brains from patients with variable time intervals
      between trauma and death were fixed in 10% formaldehyde. Sections from the
      contusioned area and from the corresponding area of the contralateral hemisphere
      were embedded in paraffin and 50 non-traumatized brains were used as controls.
      After sectioning and embedding, 10 microns sections were stained with haemalum
      and eosin (HE) and phosphotungstic acid-hematoxylin (PTAH). Stained fibrinous
      microthrombi were counted in each hemisphere and in control sections. More
      microthrombi could be found in the contusioned areas of the brain than in the
      contralateral side or in control sections.

PMID- 7509621
TI  - BCNU-resistant human glioma cells with over-representation of chromosomes 7 and
      22 demonstrate increased copy number and expression of platelet-derived growth
      factor genes.
AB  - We used standard karyotypic analyses of first-division cells to identify a
      subpopulation of cells in primary malignant gliomas with over-representation of
      chromosomes 7 and 22. These cells are a minor subpopulation in the primary tumor
      but become the dominant population after treatment in vitro of the cells with the
      chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The selection
      for a cell with this specific karyotypic abnormality suggests that these
      chromosomes contain genes important to the growth of BCNU-resistant cells.
      Southern blot hybridization analyses demonstrate an increased copy number of the
      genes encoding platelet-derived growth factor (PDGF) A-chain and B-chain, which
      have been mapped to chromosomes 7 and 22, respectively. Reverse transcription
      followed by polymerase chain reaction (RT-PCR) analysis demonstrates increased
      expression of these genes. In addition, these cells secrete a mitogenic factor
      that stimulates 3H-thymidine uptake in NIH 3T3 cells. This factor is sensitive to
      anti-PDGF antibodies and beta-mercaptoethanol, but not to anti-EGF antibodies.
      These data suggest that autocrine and/or paracrine mechanisms occur in human
      malignant gliomas, and that over-expression of PDGF may play a role in the growth
      of BCNU-resistant cells in these tumors.

PMID- 7509619
TI  - Successful application of a previously derived prognostic index in the analysis
      of a randomised trial of 281 patients with high grade non-Hodgkin's lymphoma
      (HIGNHL).
AB  - BACKGROUND: The selection of patients for experimental therapies for high grade
      non-Hodgkin's lymphoma (NHL) is now recognised to be very influential in
      affecting results. We showed previously that simple clinical indices could be
      used to create an index of risk of death in a series of 972 patients. We wished
      to test this prognostic index in a subsequent randomised treatment trial of CHOP
      based chemotherapy. PATIENTS AND METHODS: 281 patients with high grade NHL
      randomised between two chemotherapy designs were followed up from 1-6 years and
      survival analysed to develop a Cox model which was then compared against the
      previously described prognostic index. RESULTS: The previous index based on age,
      sex, performance status, stage and symptoms was similar to the data-derived
      model. Three year survivals for the best (109), intermediate (93) and worst (79)
      cohorts were 69%, 50% and 24% respectively, similar to the survivals in the
      previous series. CONCLUSIONS: CHOP-based chemotherapy is probably adequate for
      around 40% of cases of high grade NHL. The prospective test of a prognostic index
      shows that we can be confident about selecting poor-risk patients for trials of
      novel therapies, including dose intensification.

PMID- 7509620
TI  - High-dose sequential chemo-radiotherapy with peripheral blood progenitor cell
      support for relapsed or refractory Hodgkin's disease--a 6-year update.
AB  - BACKGROUND: Very few studies using high-dose therapy and autologous bone marrow
      transplantation have a long (i.e., > 3 years) follow-up. We report here the 6
      year update of a study employing high-dose sequential chemo-radiotherapy in 25
      patients with poor-risk Hodgkin's disease. PATIENTS AND METHODS: All patients
      were either refractory (7 patients) or partial responders (9 patients) or early
      relapses (9 patients) following induction chemotherapy consisting of MOPP/ABVD in
      20 patients and MOPP/ABVD followed by salvage CEP for the remaining 5 patients.
      The high-dose chemo-radiotherapy regimen employed consisted in the rapid
      sequential administration of high-doses of cyclophosphamide, methotrexate,
      etoposide and total body irradiation plus melphalan. RESULTS: As compared to 4
      year results, the 6-year probabilities of relapse-free survival, freedom from
      progression and overall survival were almost superimposable. In fact, during the
      two additional years elapsed since prior survey, only one event occurred (fatal
      cerebral hemorrhage) that was unrelated to Hodgkin's disease. In particular, the
      proportion of patients remaining event-free was 78% for those with short initial
      complete response and 31% for patients who had failed initial MOPP/ABVD.
      According to previous experience, both groups have a very low or no chance of
      long-term event-free survival when treated with standard-dose salvage
      chemotherapy. CONCLUSIONS: The very favorable long-term results of the high-dose
      sequential regimen together with its excellent tolerability and lack of early or
      late fatal toxicities, will assist clinicians in defining optimal timing for high
      dose therapy in the management of Hodgkin's disease. According to a revised
      cost/benefit analysis, it would appear that, at present, the best timing of high
      dose sequential therapy in patients failing MOPP/ABVD is at first early relapse.

PMID- 7509622
TI  - Cloning of a breakpoint cluster region at band 3q27 involved in human non
      Hodgkin's lymphoma.
AB  - In a previous cytogenetic analysis, we showed the recurrence of translocations
      involving band 3q27 and immunoglobulin gene regions in 20 out of 319 patients
      with non-Hodgkin's lymphoma (NHL). We report here the molecular cloning of the
      translocation breakpoint from tumor cells of a patient (LAR) with
      t(3;14)(q27;q32) and the isolation of DNA probes which identify a major
      translocation cluster region (MTC) at band 3q27. A DNA library from LAR tumor
      cells was screened with a JH probe and several clones were identified
      corresponding either to a somatic rearrangement of JGH genes (V4-D2-J6-C mu
      clonal rearrangement) or to the t(3;14). Analysis of the t(3;14) breakpoint
      showed that chromosome 3 material was translocated to an inverted 14q32 VH
      containing fragment which was itself translocated to the J3 gene. Chromosome 3
      assigned probes were used to investigate local DNA rearrangements in a series of
      NHL with 3q27 translocations. Rearrangements were detected in 13 of 17 patients
      including 9 of 11 with t(3;14)(q27;q32), 1 of 2 with t(2;3)(p12;q27), 1 of 2 with
      t(3;22)(q27;q11), and 2 of 2 NHL with translocations not involving an IG gene,
      namely, t(3;4)(q27;p11) and t(3;7)(q27;p12). The finding of this MTC should be
      useful for diagnostic and prognostic studies and for the identification of a
      novel oncogene at band 3q27 involved in the development of B cell NHL.

PMID- 7509623
TI  - Carcinogen-induced amplification of SV40 DNA inserted at 9q12-21.1 associated
      with chromosome breakage, deletions, and translocations in human uroepithelial
      cell transformation in vitro.
AB  - The fate of integrated SV40 viral genome in SV40-immortalized human uroepithelial
      cells (SV-HUC) during multistep chemical transformation in vitro was studied. We
      previously reported that exposure of SV-HUC at passage (P) 15 to the chemical
      carcinogens 3-methylcholanthrene (MCA), 4-aminobiphenyl (ABP), or the N-hydroxy
      metabolites of ABP causes tumorigenic transformation and/or neoplastic
      progression. We report now that these same chemical carcinogens induce
      amplification of SV40 DNA in SV-HUC. We used fluorescence in situ hybridization
      (FISH) to show that this amplification occurs at the SV40 integration site, which
      was mapped near a common fragile site at 9q12-21.1 on the der(9)t(8;9) chromosome
      that is present in all SV-HUC at the earliest passage studied. Karyotypic
      analysis, along with FISH, also revealed that all carcinogen-induced tumors (T-SV
      HUCs) had breaks at 9q12-21.1, deletions of 9q12-21.1-->pter, and new derivative
      chromosomes containing SV40 in the segment 9q12-21.1-->9q34::8q22-->8qter.
      Southern blot analysis, along with FISH, confirmed SV40 genome rearrangements in
      T-SV-HUCs. In contrast, no 9q12-21.1 breaks were observed in control SV-HUC.
      Thus, these results associate 9q12-21.1-->pter alterations with HUC tumorigenic
      transformation. In addition, these results indicate for the first time that
      (carcinogen-induced) amplification of chromosome-integrated viral genes may
      create sites that are prone to breakage, deletions, and translocations. These
      results suggest a new mechanism by which chemical carcinogens in synergy with a
      DNA tumor virus could initiate a cascade of events that contribute to the genomic
      instability associated with tumorigenesis.

PMID- 7509624
TI  - Long-range mapping of the 11q23 region involved in chromosome aberrations in
      human tumors by pulsed-field gel electrophoresis with a yeast artificial
      chromosome.
AB  - We have previously demonstrated that the RCK gene involved in t(11;14)(q23;q32)
      and the more centromeric MLL/ALL1 gene involved in t(4;11)(q21;q23) and
      t(11;19)(q23;p13) are localized on different adjacent NotI fragments by using
      pulsed-field gel electrophoresis (PFGE) analysis with the yeast artificial
      chromosome (YAC) clone yB22B2. The PFGE analysis using the YACs of YTY17
      containing the prophobilinogen deaminase (PBGD), CBL2 and THY1 genes and yB22B2
      allowed the following ordering of genes and breakpoints from CD3 to THY1 on
      11q23: cent-CD3-ALL/MLL1-RCK-PBGD-CBL2-THY1, and the establishment of a long
      range restriction map covering these genes. In addition, we showed that the FLI1
      region involved in the t(11;22)(q24;q12) in Ewing's sarcoma was more telomeric
      region that the THY1 gene by analyzing somatic cell hybrids carrying the 11q-
      and/or 14q+ chromosome of the t(11;14)(q23;q32) translocation, and by PFGE
      analysis of the YAC clone YTY17.

PMID- 7509625
TI  - Y chromosome loss in esophageal carcinoma: an in situ hybridization study.
AB  - Carcinoma of the esophagus shows a strong male predominance and other
      epidemiologic differences from cancers arising at other sites. In this study, the
      prevalence of Y chromosome loss in 29 carcinomas of the esophagus and 53
      carcinomas arising elsewhere in the aerodigestive tract was assessed by in situ
      hybridization of formalin-fixed paraffin-embedded tissue sections. Absence of the
      Y chromosome was defined as (1) negative staining for Y in neoplastic cells with
      positive staining for Y in immediately adjacent nonneoplastic epithelial and
      stromal cells, (2) positive staining of neoplastic cells with control probes for
      chromosomes X and 17, and (3) similar results at different stringencies and
      levels of protein digestion. According to these criteria, absence of the Y
      chromosome was observed in 13 of 14 (93%) adenocarcinomas of the esophagus, 8 of
      13 (62%) squamous cell carcinomas of the esophagus, and 5 of 53 (9%) carcinomas
      arising in other sites. For the neoplasms examined, Y chromosome deletion was
      strongly and selectively associated with carcinomas, particularly
      adenocarcinomas, of the esophagus (P < .0001). These findings suggest that Y
      chromosome loss may be pathogenetically significant in these neoplasms.

PMID- 7509626
TI  - Chromosome 10 allelic loss in malignant melanoma.
AB  - The involvement of tumor suppressor genes in the progression of melanoma has been
      suggested by the frequent deletion of specific regions of the genome in melanoma.
      In this study, a panel of 18 surgically removed melanomas from 15 patients was
      analyzed for loss of heterozygosity (LOH) at 10 polymorphic loci on chromosome
      10. LOH was observed in 7 (50%) of 14 informative patients. LOH data suggested
      that melanomas from 5 patients had lost entire copies of chromosome 10, and that
      melanomas from 2 patients had lost copies of 10q. In contrast, LOH was not
      observed on chromosome 15, 20, or 21. These results are consistent with previous
      cytogenetic observations and provide indirect evidence that there is a tumor
      suppressor gene on the long arm of chromosome 10 which is relevant to melanoma
      development.

PMID- 7509628
TI  - Variant translocations of chromosome 22 in Ewing's sarcoma.
AB  - Relatively few variant translocations have been reported in primary Ewing's
      sarcomas (ES). We report two new variant translocations, both of which involve
      chromosomal rearrangements of 22q12. Cytogenetic studies of tumor cells from a 12
      year-old girl revealed a variant translocation, t(7;22)(p22;q12), the second
      example reported of a simple variant of the 22q12 reciprocal translocation in
      this type of sarcoma. The identity of this rearrangement was confirmed by in situ
      hybridization. In addition, a complex translocation was identified in a
      dysmorphic 15-year-old girl, t(4;11;22)(q21;q24;q12). No previous cases of
      variant translocations in ES have involved band 7p22 or 4q21, and there are no
      previous reports of an association between congenital abnormalities and unusual
      karyotype abnormalities in ES. Both variant translocations conserve the junction
      on the der (22), providing additional cytogenetic evidence that the sequences on
      chromosome 22 are critical.

PMID- 7509627
TI  - Extrachromosomal gene amplification in acute myeloid leukemia; characterization
      by metaphase analysis, comparative genomic hybridization, and semi-quantitative
      PCR.
AB  - A case of acute myeloid leukemia (M-3) with complex karyotypic aberrations and
      double minute (dmin) chromosomes is presented. The patient had no history of
      prior exposure to mutagenic or carcinogenic agents or of other malignancies. She
      died from CNS involvement six weeks after the initial diagnosis. We used
      comparative genomic hybridization to identify the amplified sequences presumed to
      represent the dmin of the leukemic cells; the tumor/normal ratios indicated
      increased signal intensity at 8q24. This localization prompted investigation by
      semi-quantitative PCR that revealed amplification of the MYC oncogene. The extent
      of chromosome aberrations and the oncogene amplification, both linked with poor
      prognosis, may relate to the rapid course of this patient's disease.

PMID- 7509629
TI  - Whole chromosome 17 loss in ovarian cancer.
AB  - Chromosomal deletions, associated with the loss of normal function of tumour
      suppressor genes, have been identified in a variety of both familial and sporadic
      human cancers. Although the molecular pathology of ovarian cancer is not
      understood, several studies have reported deletions in chromosome 17 in ovarian
      tumours. We have used 13 restriction site polymorphic, microsatellite, and
      variable number tandem repeat markers to make a detailed analysis of chromosome
      17 deletions in 12 benign and 19 malignant ovarian tumours. Two benign and 11
      malignant tumours were informative for at least one marker on each arm of the
      chromosome. Loss of heterozygosity (LOH) was detected in both arms (by all
      informative markers) in 5 malignant tumours from four women (three with the
      disease at FIGO stage Ia). In a further bilateral ovarian tumour a partial LOH
      affecting 17q22-q25 was present in one ovary only. By contrast to a number of
      previous studies, none of the 19 malignant and 12 benign tumours showed ERBB2
      (17q12-22) amplification. The data presented show that the loss of a whole copy
      of chromosome 17 is a frequent and relatively early event in the development of
      some ovarian cancers. This suggests the possible involvement of multiple
      chromosome 17 loci in the pathogenesis of ovarian cancer. Equally plausible is
      that the loss of a whole chromosome copy could be the product of chromosomal
      instabilities induced by loss of the normal allele of tumour suppressors, such as
      TP53, located on this chromosome.

PMID- 7509630
TI  - Deletion of 3p25-->pter in a primary follicular thyroid carcinoma and its
      metastasis.
AB  - We report the cytogenetic analysis of a follicular thyroid carcinoma and its bone
      metastasis. Both lesions had identical chromosomal abnormalities, with a
      der(3)t(2;3)(q13;p25) as the most likely primary clonal alteration. Our findings
      corroborate previous observations of frequent 3p deletions in thyroid follicular
      carcinomas and suggest that the minimal chromosomal region of loss in these
      tumors is 3p25-->pter.

PMID- 7509631
TI  - Chromosomes 1 and 16 in sporadic breast cancer.

PMID- 7509632
TI  - NMR-derived solution conformations of a hybrid synthetic peptide containing
      multiple epitopes of envelope protein gp120 from the RF strain of human
      immunodeficiency virus.
AB  - Solution conformations of a 40-residue hybrid peptide containing T-helper
      epitopes and B-cell determinants from envelope glycoprotein gp120 of human
      immunodeficiency virus (HIV) have been investigated with NMR. Peptides of this
      general design are highly immunogenic and induce HIV-neutralizing antibodies and
      T-lymphocyte responses. The 16-residue N-terminal segment of the peptide contains
      a T-helper epitope, while the 24-residue C-terminal segment is derived from the
      V3 loop of HIV strain RF and contains epitopes that elicit neutralizing
      antibodies as well as T-cell responses. On the basis of 2D proton NMR spectra
      (COSY, TOCSY, and NOESY) of the peptide in aqueous solution, the resonances of
      nearly all hydrogens are assigned. The peptide is largely disordered, but
      specific medium-range NOEs demonstrate conformational preferences in certain
      regions. Part of the N-terminal segment exhibits nascent helical conformation,
      consistent with a finding that many T-cell antigens can be modeled as amphipathic
      helices. In the V3-derived segment of the peptide, one region shows evidence of a
      tight turn conformation, corresponding to a turn found previously in V3 peptides
      of HIV strains MN and IIIB. Other conformational features are also detected in
      the V3 region, such as a stretch of beta strand and a kink that may arise from
      side-chain interactions.

PMID- 7509633
TI  - Structure and dynamics of the acyl chain of a transmembrane polypeptide.
AB  - We have used acylated analogs of gramicidin as a model to study the interaction
      between a covalently coupled fatty acid and the hydrophobic part of a membrane
      spanning protein in a bilayer environment. The acyl chain was covalently coupled
      to the C-terminal ethanolamine group of gramicidin which is located near the
      membrane interface, mimicking a situation found in acylated proteins. Either
      perdeuterated palmitic acid or palmitic acid deuterated at only C2, C3, C5-6, C7
      8, C9, or C13 was coupled to gramicidin and examined by 2H-NMR in oriented
      bilayers of dimyristoylphosphatidylcholine. In this way, quadrupolar splittings
      of deuterons at specific carbons were assigned. The quadrupolar splittings and T1
      values were compared to those of free palmitic acid in oriented bilayers, with
      and without gramicidin. The results indicate that the covalently coupled fatty
      acid is highly immobilized near the carboxyl terminus because double quadrupolar
      splittings and very low T1 values (4 ms) were found for the -CD2- deuterons at
      carbon atoms C2 and C3. Control experiments with free fatty acid showed single
      quadrupolar splittings and higher T1 values for this segment of the fatty acid.
      Molecular modeling of the carboxy-terminal segment of the covalently coupled acyl
      chain suggested that it has a defined structure with a bend near its attachment
      site. In contrast, the methyl end (C10-C16) of the covalently coupled fatty acid
      had quadrupolar splittings and T1 values very similar to those found for free
      fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509634
TI  - Sensitivity of HIV-1 reverse transcriptase and its mutants to inhibition by
      azidothymidine triphosphate.
AB  - HIV-1 reverse transcriptase can catalyze the addition of either azidothymidine
      monophosphate (AZTMP) or thymidine monophosphate (dTMP) to a primer strand
      opposite template adenosine bases. The ratio of incorporation of AZTMP to dTMP as
      catalyzed by HIV-1 reverse transcriptase has been determined to be 0.4 using an
      RNA-DNA duplex substrate prepared from oligonucleotides with sequences taken from
      the HIV-1 genome sequence. Slight variations are found for the incorporation
      ratio of the two nucleotides on other substrates. Substrates containing more than
      one adenosine in the single-stranded part of the template allow for more chances
      to incorporate AZTMP and less full-length product. Variations in the intensity of
      bands on an autoradiograph of a DNA sequencing gel corresponding to different
      positions of incorporation of AZTMP suggest that not all template adenosine
      positions offer the same level of discrimination against incorporation of AZTMP.
      A reverse transcriptase containing a set of four mutations (D67N, K70R, T215Y,
      K219Q) known to cause resistance to AZT in cell culture assays has a ratio of
      incorporation that is 0.77 +/- 0.03 times the ratio for the wild-type reverse
      transcriptase opposite one specific template adenosine. In contrast, a hybrid
      mutant containing the same four mutations that cause resistance to AZT and an
      additional mutation, Y181C, which by itself causes resistance to the non
      nucleoside inhibitor L-697,661 [Sardana et al. (1992), J. Biol. Chem. 267, 17526
      17530], has a ratio of incorporation that is 1.34 +/- 0.01 times that of the wild
      type, indicating that the hybrid mutant enzyme is more susceptible to inhibition
      by AZTTP than the wild-type reverse transcriptase.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7509635
TI  - Thermodynamic and kinetic analysis of the SH3 domain of spectrin shows a two
      state folding transition.
AB  - The folding and unfolding reactions of the SH3 domain of spectrin can be
      described by a two-state model. This domain is a beta-sheet barrel containing 62
      amino acids. Equilibrium unfolding by urea, guanidine hydrochloride, and heat is
      completely reversible at pH values below 4.0. At higher pH values the unfolding
      is reversible as long as the protein concentration is below 1 mg/mL. The Gibbs
      energy of unfolding in the absence of denaturant, delta GH2O, at pH 3.5 and 298 K
      is calculated to be 12 kJ mol-1 for urea, chemical, and temperature denaturation.
      The stability of the protein does not change noticeably between pH 5.0 and 7.0
      and is around 15.5 kJ mol-1. Since heat effects of unfolding are relatively small
      and, as a result, heat-induced melting occurs in a wide temperature range, the
      analysis of scanning calorimetry data was performed taking into account the
      temperature dependence of unfolding delta Cp. The free energy of unfolding
      obtained for this domain (delta GH2O = 14 +/- 2 kJ mol-1) was, within
      experimental error, similar to those obtained in this work by other techniques
      and with those reported in the literature for small globular proteins. Kinetics
      of unfolding and refolding at pH 3.5, followed both by fluorescence and by
      circular dichroism, provide evidence of the simplest folding mechanism consistent
      with the two-state approximation. A value for delta GH2O = 13 +/- 0.7 kJ mol-1
      can be extrapolated from the kinetic data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509637
TI  - A protein from Tetrahymena thermophila that specifically binds parallel-stranded
      G4-DNA.
AB  - G4-DNA is a parallel, four-stranded structure mediated by tetrads of hydrogen
      bonded guanines (G-quartets). An abundant protein called Tetrahymena G4 binding
      protein (TGP) that binds to an intermolecular, quadruplex form of
      d(TTGGGGTTGGGGTTGGGGTTGGGG) under physiological salt conditions has been
      identified in cellular extracts from the ciliated protozoan Tetrahymena
      thermophila. In binding competition experiments, molecules capable of forming G4
      structures compete for binding to TGP, but non-G4-forming molecules and r(U2G4)4
      do not. TGP binding also requires a single-stranded region adjacent to the G4
      structure. During the course of this study, it was determined that Mg2+
      facilitates the formation of parallel-stranded G4-DNA structures and that high
      oligonucleotide concentrations are not required to drive formation of these
      structures. In addition, G4-DNA and TGP/G4-DNA complexes form readily under
      physiological salt conditions. These data support the proposal that G4-DNA
      structures exist in vivo.

PMID- 7509636
TI  - A novel modified nucleoside found at the first position of the anticodon of
      methionine tRNA from bovine liver mitochondria.
AB  - Methionine tRNA was purified from bovine liver mitochondria, and its nucleotide
      sequence was determined. The tRNA possesses only three posttranscriptionally
      modified nucleosides, two pseudouridines in the anticodon and T stems and a
      previously unknown nucleoside specified by the gene sequence as cytidine, in the
      first position of the anticodon. Structure analysis of the anticodon nucleoside
      by mass spectrometry revealed a molecular mass 28 Da greater than that of
      cytidine, and unmodified ribose, with substitution at C-5 implied by hydrogen
      deuterium exchange experiments. Proton NMR of the intact tRNA showed presence of
      a formyl moiety, thus leading to the candidate structure 5-formylcytidine (f5C),
      not a previously known compound. The structure assignment was confirmed by
      chemical synthesis and comparison of data from combined HPLC/mass spectrometry
      and proton NMR for the natural and synthetic nucleosides. The potential function
      of f5C in the tRNA(Met) anticodon is discussed with regard to codon-anticodon
      interactions.

PMID- 7509638
TI  - Protein tyrosine phosphatase substrate specificity: size and phosphotyrosine
      positioning requirements in peptide substrates.
AB  - The structural requirements of substrates for two recombinant protein tyrosine
      phosphatases (PTPases) are probed using various-sized synthetic phosphotyrosine
      (pY)-containing peptides corresponding to the autophosphorylation site in EGF
      receptor (EGFR) at Y992. The peptide EGFR988-998 (DADEpYLIPQQG) is chosen as a
      template due to its favorable kinetic constants. The contribution of individual
      amino acids on both sides of pY to binding and catalysis was assessed by kinetic
      analysis using a continuous, spectrophotometric assay. For both Yersinia PTPase
      and a soluble recombinant mammalian PTPase of 323 amino acid residues (rat PTP1),
      efficient binding and catalysis required six amino acids including the pY
      residue, i.e., four residues N-terminal to pY and one residue C-terminal to pY.
      Thus, PTPase substrate specificity is primarily dictated by residues to the N
      terminal side of pY. The pY moiety and the rest of the peptide interact with
      PTPases in a cooperative manner. The presence of pY in the peptide substrate is
      necessary but not sufficient for high-affinity binding, since phosphotyrosine and
      other simple aryl phosphates exhibit weak binding, and dephosphorylated peptides
      do not bind to PTPases. Two variations on the pY moiety are also examined in
      order to assess their utility in PTPase inhibitor design. It is demonstrated that
      the thiophosphoryl analog in which one of the phosphate oxygens is replaced by
      sulfur can be hydrolyzed by PTPases, whereas the phosphonomethylphenylalanine
      analog in which the tyrosyl oxygen is replaced by a CH2 group is a competitive
      and nonhydrolyzable inhibitor, with Ki values of 18.6 and 10.2 microM,
      respectively, for the Yersinia PTPase and the rat PTP1.

PMID- 7509641
TI  - Unilateral atrophy of the optic nerve associated with retrograde and anterograde
      degenerations in the visual pathways in Slc: Wistar rats.
AB  - Unilateral degenerative atrophy of the optic nerve (ON) occurred in 6 of 80 male
      and 4 of 80 female Slc: Wistar rats. Two of these cases completely lost the
      intracranial portion of the unilateral ON and the remainder had the small ON. The
      optic disc and ON were located histologically in the posterior pole of the
      eyeball of 2 rats with no intracranial ON. ON lesions in all cases were
      characterized by a reduced number of axons with a small number of myelinated
      axons and marked astrogliosis. There were also swelling, fragmentation and
      spheroid formation of axons, as well as thickening of the connective tissue
      sheaths and vessel walls in the ON. One side of the optic chiasma and optic tract
      contralateral to the affected ON reduced in volume, became degenerated and were
      accompanied by gliosis. Focal or diffuse degeneration of the retina was observed
      in the eyeballs with affected ON. Retinal ganglion cells decreased in the number
      showing chromatolysis. These retinae became thin and developed degeneration of
      both inner and outer portions with sclerotic changes in the retinal vessels. The
      ophthalmic and ciliary arteries in the eyeballs with affected ON often developed
      proliferative or occlusive endoarteritis, suggesting that retinal lesions may
      have resulted not only from axonal degeneration in the ON but also from ischemia.
      Histologic lesions suggestive of transneuronal degeneration were found in the
      contralateral lateral geniculate body and rostral colliculus. Based on the data
      presented, it was presumed that a primary lesion may have been induced in the ON
      by a circulatory disturbance and followed by retrograde and anterograde
      degenerations in the visual pathways.

PMID- 7509639
TI  - Differences in the cross-linking activities of native and recombinant Erythrina
      corallodendron lectin with asialofetuin. Evidence for carbohydrate-carbohydrate
      interactions in lectin-glycoprotein complexes.
AB  - A previous study showed that several multivalent galactose-specific lectins
      including the 14-kDa lectin from calf spleen and the lectins from Erythrina
      indica, Erythrina cristagalli, and soybean agglutinin formed specific cross
      linked complexes with the glycoprotein asialofetuin (ASF) [Mandal, D. K., &
      Brewer, C. F. (1992) Biochemistry 31, 8465-8472]. In the present study, we have
      used quantitative precipitation analysis to compare the cross-linking activities
      of the Gal/GalNAc-specific lectin from Erythrina corallodendron (ECorL) and the
      recombinant protein (rECorL) which lacks the covalently linked heptasaccharide
      chains of the native lectin, with ASF. At low concentrations of ASF relative to
      the lectin, native dimeric ECorL binds to each of the three terminal Gal residues
      of the three N-linked triantennary chains of ASF and precipitates as a cross
      linked complex at a ratio of 1:9 ASF/lectin (monomer). With increasing
      concentrations of ASF, the 1:9 complex changes to a 1:3 ASF/lectin complex, and
      at higher ASF concentrations, a 1:1 cross-linked complex forms. However, rECorL,
      which possesses the same specificity and binding affinity as the native lectin,
      forms only the 1:9 and 1:3 ASF/lectin complexes. Other Erythrina lectins
      examined, all of which have covalently attached carbohydrate and are structurally
      similar to ECorL, show the same cross-linking behavior as native ECorL. On the
      other hand, the dimeric 14-kDa calf spleen lectin which lacks covalently attached
      carbohydrate forms only 1:9 and 1:3 cross-linked complexes with ASF [Mandal, D.
      K., & Brewer, C. F. (1992) Biochemistry 31, 8465-8472].(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7509640
TI  - Evaluation of serum amyloid A protein as an acute-phase reactive protein in
      horses.
AB  - Serum amyloid A protein (SAA) was isolated from equine acute-phase serum by
      repeating Sephadex G-75 gel filtration 3 times. Quantitative measurement of
      equine SAA was performed by the single radial immunodiffusion technique with
      rabbit anti-equine SAA serum. In clinically normal horses, the SAA concentration
      remained relatively high from immediately after birth up to 1 week of age. After
      this the concentration showed periodic fluctiation in the range of approximately
      13 to 30 micrograms/ml. The mean (+/- SD) concentration of SAA in foals (< or =
      12 months old) and in adult horses (> or = 18 months old) was 19.37 +/- 9.41 and
      21.53 +/- 9.81 micrograms/ml, respectively. In mares during the perinatal period,
      the SAA concentration remained stable and within the normal range for 4 months
      before parturition. After foaling, it increased quickly and reached a peak value
      of 136.78 +/- 56.74 micrograms/ml on day 3 postpartum, and then began to decrease
      at 2 weeks postpartum returning to within the normal range by 1 month postpartum.
      In horses with experimentally induced inflammation, the SAA concentration
      increased quickly, and reached the highest value, approximately 4 to 20 times
      higher than pre-treatment values, on day 2 after treatment. It then returned to
      the base line values within 10 days to 4 weeks, concurrent with the disappearance
      of local inflammatory signs. The SAA concentration was very high in most horses
      with clinical signs of inflammation. It was concluded from these data that equine
      SAA was a sensitive acute-phase reactive protein which increased in the early
      phase of various acute inflammations.

PMID- 7509642
TI  - [Effect of autoinducers of anabiosis for some microorganisms on rat liver
      mitochondria respiration].
AB  - 2-(4-Hydroxyphenyl)ethane-1-ol (tyrosol) and 5-n-alkyl(C19,C21)resorcinols
      produced by some microorganisms as anabiosis autoregulators (factors d1) inhibit
      the electron transport and uncouple oxidative phosphorylation in the respiratory
      chain of rat liver mitochondria: a 50% decrease of the respiratory control is
      caused by 0.32-0.36 mumol of tyrosol or by 0.21-0.26 mumol of alkylresorcinols
      per mg of protein. Alkylresorcinols reduce the NADH-dehydrogenase and succinate
      dehydrogenase activities in mitochondria, whereas tyrosol acts predominantly on
      the NADH-dehydrogenase activity.

PMID- 7509643
TI  - [Intensification of the effect of exogenous plasminogen activators on lysis of
      fibrin blood clots due to a decrease in the level of alpha-2- antiplasmin by a
      plasmasorption method].
AB  - Using plasminogen-Sepharose 4B chromatography, a 50-70% reduction in the alpha-2
      antiplasmin (alpha-2-AP) content in human and dog blood plasma was reached. The
      decrease in the alpha-2-AP concentration in human and dog blood plasma markedly
      enhanced the lysis of fibrin clots formed from the plasma under the action of
      urokinase and streptokinase. Thus, the lysis of model clots for a definite period
      of time for human and dog blood plasma depleted for alpha-2-AP by 50-70% required
      5-8 and 3-6 times as low urokinase and streptokinase concentrations as those
      needed for the clot lysis in the native plasma. The decrease in the fibrinogen
      concentration in human blood plasma caused by plasmosorption on plasminogen
      Sepharose enhanced the model fibrin clot lysis by urokinase and streptokinase,
      however, by no more than 5-10%. Hence, the increased efficiency of plasminogen
      activators in the given model system can be accounted for by the decline of the
      antiplasmin potential of the blood plasma.

PMID- 7509644
TI  - Both cytochromes P450 2E1 and 1A1 are involved in the metabolism of
      chlorzoxazone.
AB  - Chlorzoxazone, a centrally acting muscle relaxant, was previously shown to be
      hydroxylated on carbon 6 specifically by cytochrome P450 2E1. Accordingly, this
      drug has been proposed as a potential noninvasive in-vivo probe for screening the
      hepatic P450 2E1 activity. This study was carried out to test the specificity of
      such a substrate when first experiments conducted by using human hepatocyte
      cultures showed that the chlorzoxazone 6-hydroxylation activity increased after 3
      methylcholanthrene treatment of cells. Indeed, the ability of both rat and human
      hepatocytes to metabolize chlorzoxazone significantly increased after treatments
      by 3-methylcholanthrene alone or plus ethanol, suggesting the involvement of P450
      1A enzymes in this oxidative reaction. Identical results were obtained by in-vivo
      treatment of rats with four inducers of P450 1A enzymes, namely, beta
      naphthoflavone, isosafrole, Arochlor 1254, and 3-methylcholanthrene. Furthermore,
      the chlorzoxazone 6-hydroxylation activity was inhibited by both alpha
      naphthoflavone and dimethyl sulfoxide, both known to inhibit P450 1A and P450 2E1
      activities, respectively. Finally, the use of yeasts genetically engineered for
      expression of human P450 1A1, 1A2, 2C9, and 3A4 demonstrated that P450 1A1 was
      significantly involved in this catalytic activity. In conclusion, these results
      taken together suggest that chlorzoxazone should be used with precaution as in
      vivo tool for evaluating P450 2E1. However, the relative Km of P450 1A1 and 2E1
      for chlorzoxazone and, on the other hand, the relative levels of these two
      enzymes in the human liver suggest that P450 2E1 would generally be the major
      form metabolizing chlorzoxazone in-vivo.

PMID- 7509645
TI  - [The participation of opioid peptides in forming the nonspecific protective
      reactions of the body].
AB  - The mechanisms of action of the opioid system on forming the nonspecific
      protective reactions of the body were investigated in rabbits and CBA mice
      injected the native preparation interleukin-1 (IL-1) of the rabbit after
      preinjection to the same animals with synthetic analog of leu-enkephalin-
      dalargin (D) or naloxone. Injection of D with IL-I to mice produced a 1.5 lower
      content of C-reactive protein (CRP) than in the control. Naloxone injected with
      saline or D prior to IL 1, prevented IL-1-induced rise in CRP level. The property
      of IL-1 was found to slow down process of summation of peripheral nociceptive
      impulses in the CNS of rabbits after i.v. injection the pyrogenic dose of IL-1.
      The preinjection of naloxone blocked these phenomenon and pyrogenic effect of IL
      1 in the rabbits. The effects observed are supposed to result from the
      interaction of leukopeptides and opioid peptides at the level of cell receptors.

PMID- 7509646
TI  - [Increased myocardial resistance to ischemia in a chronic model of stenocardia].

PMID- 7509647
TI  - [The autoregulation of the coronary flow of the isolated rat heart after NO
      synthase blockade].
AB  - The experiments were performed on 67 rat hearts isolated by the Langendorff
      method. Perfusion pressure (PP) was stepwise increased from 40 to 120 mm Hg. It
      was found that NO-synthase blockade by NG-monomethyl-L-arginine (NG-MMLA)
      decreased volume velocity coronary flow (VVCF) at PP 40 and 60 mm Hg,
      autoregulation index and shifted the onset of effective autoregulation to the
      right. In cases of high coronary tone, caused by introduction of pituitrine, the
      autoregulation and its effectiveness was unchanged. The combination of NG-MMLA
      and pituitrine decreased the autoregulation index again. In cardiac perfusion
      under constant pressure, the value of maximal hyperemic coronary flow after
      introduction of NG-MMLA was decreased by 30-57%, and as a result the coronary
      reserve was decreased by 28.3%. Thus, NO, which released from endothelium of
      coronary vessels plays a significant role in mechanism of coronary
      autoregulation.

PMID- 7509648
TI  - [A theoretical analysis of the possible mechanisms of interferon induction in
      priming and blocking].

PMID- 7509649
TI  - [An analysis of the mechanism of the resistance to barbiturate action by using
      exogenous RNA].
AB  - For the first time the experimental method of exogenous RNA has been used to
      evaluate the role of protein synthesis in different organs for the development of
      resistance to the soporific effect of barbiturates. Liver cytosolic RNA of
      phenobarbital-treated donors was found to reproduce completely the effect of
      phenobarbital-induced resistance to barbiturates in recipient rats: the reduction
      of hexenal-induced sleep and the increase of cytochrome P450 content in hepatic
      microsomes. Brain and renal RNAs had no influence on recipients. These data
      demonstrate the decisive role of microsomal R450-contained enzymes synthesis in
      the mechanism of the development of barbiturate resistance. It is concluded that
      exogenous RNA technique is of value for the organ-specific analysis of various
      complicated biological phenomena resulted from the activation of protein
      synthesis. The mechanism of exogenous RNA action and the possibility of cellular
      interactions by means of RNA molecules are also discussed.

PMID- 7509650
TI  - [The content of the PAMG-1 protein that binds insulin-like growth factor I
      (somatomedin C) in the blood serum of diabetic patients].
AB  - The study was undertaken to measure PAMG-1 (PP 12, IGEBP-1) that is insulin-like
      growth factor binding protein in blood sera of diabetic patients. We could show a
      stable significant (10-fold or more in 54% of patients) increase of PAMG-1
      concentrations in patients suffering with insulin-dependent diabetes and a
      moderate (1.5-2 times) increase of PAMG-1 levels in 80% of patients suffering
      with non-insulin-dependent diabetes. Significant individual differences of DAMG-1
      serum concentrations were also demonstrated (10-230 mg/ml in insulin-dependent
      and 0-360 ng/ml in non-insulin-dependent diabetes).

PMID- 7509651
TI  - [The mite allergen and allergoid stimulation of histamine secretion by mast
      cells].
AB  - Rat peritoneal mast cells were incubated with serum from highly mite-sensitive
      patients. It was demonstrated that exposure of passive sensitized mast cells to
      allergen from mites Dermatophagoides farinae induced the release of histamine.
      Exposure of mast cells to 10 micrograms/ml and 50 micrograms/ml mite allergen
      resulted in an increase of histamine secretion to 48% of the basal level. The
      allergoid (formaldehyde-modified mite allergen) had poor histamine-releasing
      activity compared to allergen. The allergoid (50 micrograms/ml) induced a 2.5
      fold decrease in histamine release. The allergen at the same concentrations and
      the same release as allergen in dose 0.1 microgram/ml.

PMID- 7509652
TI  - Flexible granulocyte colony-stimulating factor dosing in ovarian cancer patients
      who receive dose-intense taxol therapy.
AB  - As has been reported with other chemotherapeutic agents, evidence is emerging to
      suggest that increased taxol dose intensity is associated with improved
      therapeutic efficacy. Granulocyte colony-stimulating factor (G-CSF) effectively
      protects the bone marrow from taxol-induced neutropenia and allows for higher
      taxol dose administration. This report addresses the optimal use of G-CSF as a
      supportive agent for dose-intense taxol therapy. Forty-seven patients were
      evaluated. Each ovarian cancer patient received taxol with G-CSF support, with
      starting doses of 250 mg/m2 per 21 days and 10 micrograms/kg/d, respectively.
      Five patients were treated with the same dose of G-CSF for multiple cycles. Forty
      two patients were given "flexible" G-CSF dosing. Instead of reducing taxol dose
      after a cycle of therapy complicated by febrile neutropenia (F+N+), the G-CSF
      dose was increased. Only after a second episode of F+N+ was the taxol dose
      reduced. The initial 5 patients who developed F+N+ after taxol (250 mg/m2) and G
      CSF (10 micrograms/kg/d) were retreated at the same doses of both drugs;
      subsequently, 4 of 5 patients had another episode of F+N+. With flexible G-CSF
      dosing, taxol dose intensity could be maintained at the target level in 34 of 42
      patients (81% of the cohort). Sixteen of these patients (38% of the cohort) would
      have required taxol dose reductions for F+N+ if flexible G-CSF dosing had not
      been used. By increasing the G-CSF dose when indicated, patients at high risk for
      recurrence of F+N+, because they had already experienced one episode, appeared to
      have a lower risk of developing a recurrent episode. These data suggest that
      flexible G-CSF dosing may have merit and may allow the administration of more
      dose-intense taxol. A prospective, randomized, controlled clinical trial of
      flexible G-CSF dosing versus fixed-dose G-CSF appears warranted.

PMID- 7509653
TI  - Signaling and induction of enhanced cytoadhesiveness via the hematopoietic
      progenitor cell surface molecule CD34.
AB  - The transmembrane glycoprotein CD34 shows a highly restricted expression on a
      crucial subset of hematopoietic cells. We show here that engagement of particular
      determinants of CD34 can lead to signal transduction and to enhanced adhesiveness
      of CD34+ hematopoietic cells. Monoclonal antibodies (MoAbs) directed against O
      sialoglycoprotease-sensitive epitopes of CD34 (QBEND10, ICH3, BI.3C5, MY10) but
      not MoAbs against O-sialoglycoprotease-resistant epitopes (9F2, 8G12) induce
      actin polymerization in KG-1a and KG-1 cells and strongly enhanced
      cytoadhesiveness. The capacity to induce adhesion requires cellular energy,
      divalent cations, and intact cytoskeleton but not de novo protein synthesis. The
      observed cytoadhesion seems at least in part to be caused by a concomitant
      activation of the beta 2 integrin cytoadhesion pathway. It can be significantly
      inhibited with lymphocyte function-associated antigen-1 and intercelluar adhesion
      molecule-1 antibodies. Protein kinase inhibition analyses suggest that the
      pathways initiated by engagement of the CD34 molecule with certain CD34 MoAbs
      involves protein tyrosine kinases but that protein kinase C is not critically
      involved.

PMID- 7509654
TI  - Detection and characterization of apoptotic peripheral blood lymphocytes in human
      immunodeficiency virus infection and cancer chemotherapy by a novel flow
      immunocytometric method.
AB  - We have developed a quantitative and sensitive flow cytometric method for the
      detection of human apoptotic lymphocytes that, unlike previously described
      assays, allows their identification in mixed populations of peripheral blood
      leukocytes as well as their immunophenotyping. Apoptotic lymphocytes are
      identified on the basis of peculiar light scatter changes, reflecting their
      smaller size and their modified nucleus/cytoplasm organization, and of the
      decreased expression of surface CD45 molecules. Based on these criteria,
      apoptotic lymphocytes generated by exposure to ionizing radiation can be easily
      distinguished from viable cells and from necrotic lymphocytes generated by
      treatment with antibody and complement. Using this assay, we reappraised the
      phenomenon of the in vitro apoptosis of lymphocytes from patients with human
      immunodeficiency virus (HIV) infection. Lymphocytes from HIV patients, unlike
      those from normal HIV-negative subjects, undergo apoptosis upon simple in vitro
      culture. We found that the percentages of lymphocytes undergoing apoptosis were
      significantly higher in patients with low CD4 cell counts (< 400/microL) than in
      patients at earlier stages (> 400 CD4 cells/microL). However, phenotypic analysis
      disclosed that apoptotic lymphocytes generated in these cultures were mostly CD8+
      T cells and CD19+ B cells. Thus, in contrast to what has been previously
      suggested, the phenomenon of in vitro lymphocyte apoptosis might not be
      pathogenetically related to the depletion of CD4+ T cells in acquired
      immunodeficiency syndrome. Nevertheless, it might represent an useful marker of
      disease progression. Our assay allows the analysis of unfractionated peripheral
      blood leukocytes and thus the identification of apoptotic lymphocytes circulating
      in vivo. Apoptotic lymphocytes could indeed be detected in the circulation of a
      patient with cancer shortly after high-dose cytotoxic chemotherapy. By contrast,
      no apoptotic lymphocytes could be detected in vivo in patients with early or
      advanced HIV infection.

PMID- 7509655
TI  - Anti-CD19 inhibits the growth of human B-cell tumor lines in vitro and of Daudi
      cells in SCID mice by inducing cell cycle arrest.
AB  - In this report, we extend our previous findings that IgG or F(ab')2 fragments of
      HD37 anti-CD19 antibody (Ab) in combination with the immunotoxin (IT), RFB4-anti
      CD22-deglycosylated ricin A chain (dgA) (but neither reagent alone), prolonged
      the survival of SCID mice with disseminated human Daudi lymphoma (SCID/Daudi
      mice) to 1 year at which time they still remained tumor-free. We explored the
      mechanisms by which the HD37 Ab exerts antitumor activity in vivo by studying its
      activity in vitro. We found that it has antiproliferative activity (IC50 = 5.2 -
      9.8 x 10(-7) mol/L) on three CD19+ Burkitt's lymphoma cell lines (Daudi, Raji,
      and Namalwa) but not on a weakly CD19-positive (CD19lo) pre-B cell tumor (Nalm
      6). The inhibitory effect was manifested by cell cycle arrest, but not apoptosis.
      Results using three additional anti-CD19 Abs, suggest that the affinity of the
      antibody and possibly the epitope which it recognizes may effect its capacity to
      transmit a signal that induces cell cycle arrest. Hence, therapeutically useful
      Abs may exert anti-tumor activity by a variety of mechanisms, each of which
      should be evaluated before undertaking clinical trials in humans.

PMID- 7509656
TI  - Identification of Philadelphia-negative granulocyte-macrophage colony-forming
      units generated by stroma-adherent cells from chronic myelogenous leukemia
      patients.
AB  - Chronic myelogenous leukemia (CML) is a clonal disorder of the hematopoietic stem
      cell characterized by the coexistence of Philadelphia-negative (Ph-) with Ph+
      progenitors. CML progenitor cells have been shown to be defective in adherence to
      marrow stroma. The present study investigated at the cytogenetic level marrow
      derived CML clonogenic cells generated from the stroma-adherent cell fraction. On
      direct cytogenetic analysis, the overall mean (+/- SEM) percentage of Ph-
      metaphases was 3% +/- 1%. Mononuclear marrow cells from CML patients (n = 18)
      were incubated with mafosfamide (100 micrograms/mL) or control medium, seeded
      onto marrow stromal layers and allowed to adhere (2 hours, 37 degrees C). After a
      short-term (3-day) liquid culture, the cells were harvested, incorporated in
      methyl-cellulose, and individual colonies were analyzed by single colony
      karyotyping. The mean (+/- SEM) percentage of Ph- colonies generated from the
      stroma-adherent fraction was 35% +/- 6%. As compared with marrow colony-forming
      unit granulocyte-macrophage plated before any manipulation, the mean (+/- SEM)
      percentage of Ph- clones was significantly increased by stroma adherence (35% +/-
      6% v 15% +/- 4%, P < or = .005) and mafosfamide (100 micrograms/mL) incubation of
      marrow cells before stroma adherence (58% +/- 9% v 35% +/- 6%, P < or = .005). An
      additive effect was observed by combining mafosfamide treatment and stroma
      adherence. Single-colony transfer experiments showed that 50% +/- 4% stroma
      adherent and 70% +/- 4% stroma-adherent mafosfamide-treated progenitors gave rise
      to secondary colonies. To further characterize the stroma-adherent fraction,
      experiments were performed in which CD34+ marrow cells were used. The mean (+/-
      SEM) output of progenitors generated by 10,000 CD34+, stroma-adherent cells was
      888 +/- 188 and 570 +/- 258 for untreated and mafosfamide-treated cells,
      respectively. Individual colonies were analyzed by single-colony karyotyping and
      fluorescent in situ hybridization using a biotinylated cosmid DNA probe that
      hybridize to abl oncogene. The CD34+, stroma-adherent fraction contained 38% +/-
      14% (untreated) and 56% +/- 18% (mafosfamide-treated) (P < or = .025) Ph-
      progenitors. In conclusion, the present data show the possibility to select Ph-
      clones that (1) have a maintained capability of stroma adherence, (2) are
      mafosfamide resistant, (3) are derived from the CD34+ fraction, and (4) have high
      replating potential.

PMID- 7509657
TI  - Multipin technology in the preparation and screening of peptide libraries.
AB  - Peptide libraries are relatively new sources of enormous numbers of unique
      compounds, fodder for the mill of drug discovery programs. Their enormous
      diversity derives from vast numbers of combinations of a small number of monomers
      (Geysen et al., 1986). For example, a complete hexapeptide library synthesized
      from just 10 monomers (amino acids) has one million unique compounds in it. In
      principle, other types of combinatorial libraries can have equally vast numbers
      of members; for example, the monomers can be N-acyl glycines, giving rise to the
      so-called "peptoids" (Simon et al., 1992); or the monomers could be
      monosaccharides or nucleotides.

PMID- 7509658
TI  - Novel specificities of Mucor hiemalis endo-beta-N-acetylglucosaminidase acting
      complex asparagine-linked oligosaccharides.
AB  - Mucor hiemalis endo-beta-N-acetylglucosaminidase (Endo-M) was proved to act on
      complex type biantennary oligosaccharides of glycoproteins by using dansylated
      asparagine-linked and pyridylaminated oligosaccharides, as the substrate. The
      enzyme could act on both asialo- and sialo-biantennary oligosaccharides. This is
      the only endo-beta-N-acetylglucosaminidase known to act on sialo glycans, though
      their activity for them was weak. The enzyme could liberate complex type
      biantennary oligosaccharides from native human asialotransferrin, which was
      ascertained by a combination of the pyridylaminated method and HPLC. The enzyme
      had substrate specificity for high-mannose type oligosaccharides different from
      those of the endo-beta-N-acetylglucosaminidases of other microorganisms:
      ovalbumin glycopeptide-IV was a better substrate for Endo-M than glycopeptide-V.
      The enzyme could act on complex type triantennary oligosaccharides of dansylated
      glycopeptide prepared from calf fetuin. The enzyme had various novel
      specificities in regard to activities on complex type and high-mannose type
      oligosaccharides in glycoproteins.

PMID- 7509660
TI  - Preventive medicine in Croatia through time and space.
AB  - The Croatian preventive medicine was well-known in the world through history. It
      was famous from the time of the quarantine in Dubrovnik, through sanitary cordon
      and contribution in obligatory first immunization against smallpox. Croatia
      presented Andrija Stampar as the leader in preventive medicine from the World War
      I till the sixties. We owe him all kinds of public health work both in
      organization and education as well as the initiating the World Health
      Organization. Knowledge and capabilities of Croatian preventive medicine workers
      were demonstrated the most clearly during the Croatian homeland war in 1991/91
      when the infectious diseases as permanent war companions did not have effect on
      the state of health of the people in Croatia.

PMID- 7509659
TI  - Alpha-fetoprotein-producing esophageal adenocarcinoma: report of a case.
AB  - This paper describes a rare case of adenocarcinoma located in the middle portion
      of the esophagus with liver metastasis. An 80-year-old man was admitted to our
      hospital with dysphagia and vomiting, following which an upper gastrointestinal
      series and esophagoscopy located an elevated-type carcinoma in the middle
      thoracic esophagus. Computed tomography revealed an esophageal tumor invading the
      left atrium and aorta, and multiple intrathoracic lymph node swellings, and an
      ultrasonograph of the liver showed multiple liver metastases. The serum
      carcinoembryonic antigen, carbohydrate antigen 19-9, and squamous cell carcinoma
      related antigen levels were normal, but the serum alpha-fetoprotein (AFP) level
      was 351.5 ng/ml. The patient died 124 days after undergoing an esophageal bypass
      operation. On post-mortem histological examination, the original esophageal tumor
      was diagnosed as a poorly differentiated adenocarcinoma without a squamous
      component and immunohistochemical staining for AFP showed positive granules in
      the cytoplasm. All the metastatic nodules, including the lymph nodes, liver,
      spleen, and lungs, showed the same histological type and AFP-staining pattern as
      the original esophageal tumor. To our knowledge, this is the first case of AFP
      producing esophageal carcinoma to be reported in Japan.

PMID- 7509661
TI  - Peripheral blood lymphocyte populations and phagocytic functions in patients with
      active alopecia areata.
AB  - The proportions and absolute number of peripheral blood CD3+, CD4+, CD8+ and
      CD16+ and CD26+ lymphocytes, large granular lymphocytes, B lymphocytes and
      phagocytic ability (ingestion and intracellular killing) were determined in 29
      patients with active alopecia areata (AA), 14 of them being free of therapy and
      15 receiving topical steroid therapy, as well as in 30 healthy individuals. The
      percentage of CD8+ cells was decreased and the CD4/CD8 ratio increased, while
      monocyte microbicidal capacity was decreased in the AA patients compared to the
      controls. The percentage of CD8+ cells remained decreased in patients free of
      therapy but returned to normal in those on therapy, while the CD4/CD8 ratio
      remained increased in both patient subgroups. The percentage of CD26+ cells was
      increased in patients free of therapy. Monocyte ingestion ability was decreased
      in patients on therapy compared to the healthy controls. Monocyte microbicidal
      capacity was normal in patient free of therapy, while in those on therapy it was
      decreased compared both to healthy controls and to patients free of therapy. The
      reported alterations in proportions of peripheral blood lymphocyte populations
      support the hypothesis of autoimmune origin of AA. Decreased monocyte phagocytic
      functions probably were induced by steroid therapy rather than by the disease per
      se.

PMID- 7509662
TI  - T-cell subsets in asthmatic children.
AB  - Using monoclonal antibodies authors determined the percentage of CD2(+)-, CD4(+)-
      and CD8(+)-lymphocytes in the peripheral blood of 45 asthmatic children. In 38
      subjects asthma was reaginic, while in 7 it was nonreaginic. The aim of the study
      was to detect an abnormality which might contribute to the pathogenesis of the
      disease. A correlation test was done to assess the association of the above
      mentioned percentages with the serum IgE level and the duration of the illness.
      The percentage of CD2(+)-lymphocytes and CD4+ lymphocytes does not differ
      significantly among the patient groups themselves nor in relation to healthy
      children. The percentage of CD8(+)-lymphocytes in asthmatic children,
      particularly in the group with reaginic asthma, is significantly lower (P < 0.01)
      than in healthy children. A significant negative correlation (P < 0.05) was found
      between the percentage of CD8(+)-cells and the serum IgE level in asthmatics.
      There was no significant correlation between the CD2(+)-lymphocyte and CD(4+)
      lymphocyte percentages and the serum IgE level, nor between any of examined
      percentages and the duration of the illness. The authors conclude that, in
      children with reaginic asthma, a primarily lower percentage of CD8(+)
      lymphocytes, which bear a suppressor function, may be one of the causes for over
      production of IgE and is therefore an important factor in the pathogenesis of the
      illness.

PMID- 7509663
TI  - Immunohistochemistry of glomus jugulare and tympanicum tumors.
AB  - Glomus jugulare and tympanicum tumors differ from other paragangliomas,
      especially from aorto-sympathetic, visceral-autonomic and adrenal medulla tumors.
      They differ not only in their localization, but also in their histologic and
      clinical pictures. As differentiated from other paragangliomas, these tumors show
      no argyrophilia. Besides the difference in histochemistry, the glomus jugulare
      and tympanicum tumors also differ from other paragangliomas in the intensity of
      their immunohistochemical reaction to particular markers. As differentiated from
      other paragangliomas that react well to chromogranin with antisera, the chief
      cells of these tumors are poorly represented with chromogranin as a marker. As
      distinguished from chromogranin, however, synaptophysin produced a positive
      reaction, i. e., moderate to maximal reactivity, in all cases under study. Helper
      cells of these tumors, and likewise other paragangliomas, are well represented by
      antisera to S-100 protein and glial fibrillary acid protein.

PMID- 7509664
TI  - Surgical treatment of Meniere's disease--two techniques compared.
AB  - Two techniques for surgical treatment of Meniere's disease, endolymphatic sac
      decompression according to Shambough and decompression on the stapes footplate,
      i. e., platino decompression according to Martin, were compared. A series of 81
      patients were hospitalized for treatment, and 20 surgical procedures were
      performed: platino decompression in eight cases, and endolymphatic sac
      decompression in 12. None of the eight patients had relapse of the disease after
      platino decompression, whereas the endolymphatic sac operation was followed by
      relapse in 6 of the 12 patients. Considering the postoperative values of hearing
      loss, the considerably lower incidence of relapse, and the technically simple
      procedure of platino decompression, this technique is recommended as a method of
      choice for the surgical treatment of Meniere's disease.

PMID- 7509665
TI  - Ventricular arrhythmias during exercise testing and daily activities in patients
      with stable angina pectoris before and during Aldisem and penbutolol treatment.
AB  - The authors investigated the prevalence of ventricular ectopic activity (VEA)
      during exercise testing and 24-hour ambulatory Holter monitoring and its relation
      with ischemic episodes during daily activities before and during therapy with
      diltiazem and penbutolol in 41 patients with stable and typical angina pectoris.
      Seven (17%) of the 41 patients had exercise-induced ventricular ectopic activity
      (EIVA). Premature ventricular complexes (PVC) Lown grade I disappeared in 6
      patients on therapy and appeared in another 6 new patients. PVC Lown grade IV A
      in one patient before therapy changed to Lown grade IV B upon therapy. There was
      no difference between patients with and without EIVA in the ages, average number
      of angina onset per day, percentage patients with exercise angina, average
      functional class, percentage of patients with exercise ST depression, average
      maximal ST depression, heart rate and systolic blood pressure at peak exercise
      and duration of exercise. The workload before therapy was similar in the 2
      groups, but was significantly greater during therapy in patients without EIVA.
      During 984 hours of recording, 185 ischemic episodes were detected in 25 patients
      before therapy, and 111 ischemic episodes in 20 patients during therapy. PVC was
      observed in 12 (48%) of the 25 patients and in 81 (27%) of the 295 ischemic
      episodes. VEA during ischemic episodes was observed in patients with and without
      baseline PVC. The ventricular arrhythmias found were more complex types during
      ischemic episodes than baseline. Thus, the incidence of VEA in patients with
      stable and typical angina pectoris was 17% during exercise and 52% during daily
      activities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509666
TI  - Analysis of projectile destructive effect in missile injury to the brain.
AB  - During the war in Croatia so far, more than 250 casualties having missile wounds
      of the brain, spinal chord and peripheral nervous system were admitted to the
      Neurosurgical Clinic, University Hospital-Rebro. These injuries were mainly
      caused by low-velocity missiles. However, the high-velocity ones, used nowadays,
      in direct injury to the head, cause destruction of the brain that is incompatible
      with survival in most of the cases. This paper deals with a patient injured by a
      7.62 mm projectile. The mechanism of the brain destruction is not completely
      clear since the missile was found at the very entrance of the missile wound,
      while the brain was destroyed up to the opposite side of the endocranium. Four
      mechanisms of the missile's effect aimed at explaining the cause of death of the
      patient, as well as the bizarre position of the missile, were taken into
      consideration. The review shows how perilous a wound from a direct missile injury
      to the head could be, regardless of its speed.

PMID- 7509667
TI  - Testicular trauma sustained during football.
AB  - Three patients having testicle injury received while playing football are
      reported. Two of them received a blow with a ball. Surgical findings revealed
      spermatic cord injury with scrotal haemorrhage in one patient, and
      intratesticular hematoma in another one. After hematoma evacuation and arrest of
      haemorrhage achieved by ligature, the testicle appeared normal. In the third case
      with testicle rupture after scrotal kick, early exploration finished with
      adequate debridement and approximation of the tunica albuginea laceration.
      Postoperative ultrasonography showed a homogeneous echo pattern of the remaining
      two-thirds of the parenchyma.

PMID- 7509668
TI  - The fastest genome evolution ever described: HIV variation in situ.
AB  - Human immunodeficiency virus is an RNA virus in which the degree of genetic
      variation observed is phenomenal--up to 20% within an infected individual. This
      is essentially due to remorseless cycles of viral replication, most probably due
      to chronic activation of the immune system. It can be estimated that the number
      of variants in existence worldwide must be in excess of 10(14)-10(18), and given
      the nature of RNA viruses even more novel variants should emerge.

PMID- 7509669
TI  - Expression of the Hermes-1 (CD44) and ICAM-1 (CD54) molecule on the surface of
      thyroid cells from patients with Graves' disease.
AB  - From studies of binding of 51Cr-labeled T cells to human thyroid monolayers, we
      have postulated the existence of tissue "homing-like" receptors on thyroid cells
      in patients with Graves' disease (GD). In this study we have investigated whether
      the CD44 (Hermes-1) protein, well known as a putative human lymphocyte homing
      receptor, is expressed on thyroid cells in patients with GD, and if so whether
      its expression is influenced by interferon-gamma (IFN-gamma). Cell surface CD44,
      as well as CD54 (ICAM-1), another putative homing receptor, antigens were
      analyzed by flow cytometry and immunohistochemistry. CD44 and CD54 were both
      expressed on thyroid cells from untreated patients with GD, which, in the case of
      CD44, appeared as two peaks. IFN-gamma treatment enhanced the expression of the
      CD54 protein on Graves' thyroid cells and inhibited the expression of the larger
      of the two CD44 peaks, but not the other. Only small amounts of CD44 and CD54
      were detected on normal thyroid cells, neither of which was affected by IFN
      gamma. The CD44 protein was also demonstrated on both GD and normal thyroid cells
      by immunohistochemistry. These findings suggest that CD44, and possibly CD54, may
      induce putative adhesion pathways that lead to the homing of lymphocytes to the
      thyroid in patients who develop Hashimoto's thyroiditis and Graves' disease.

PMID- 7509671
TI  - Detection of TSH receptor RNA in cultured fibroblasts from patients with Graves'
      ophthalmopathy and pretibial dermopathy.
AB  - Fibroblasts are target cells for the autoimmune process in Graves' ophthalmopathy
      and pretibial dermopathy. Because the autoantigen involved in the hyperthyroidism
      of Graves' disease is the TSH receptor, we sought to determine whether RNA
      encoding this receptor might be present in retroocular and pretibial fibroblasts.
      RNA was reverse transcribed and the resulting cDNA was amplified by the
      polymerase chain reaction using primers spanning a region of the extracellular
      domain of the human TSH receptor. The predicted amplified product, verified by
      direct sequencing, was detected when RNA was derived from fibroblasts, but not
      from the nonfibroblast cells studied. The demonstration in fibroblasts of RNA
      encoding this important autoantigen in Graves' disease suggests that the TSH
      receptor might play a role in the pathogenesis of the connective tissue
      manifestations of this disease.

PMID- 7509672
TI  - Propylthiouracil (PTU)-induced agranulocytosis treated with recombinant human
      granulocyte colony-stimulating factor (G-CSF).
AB  - Two premenopausal female patients with Graves' hyperthyroidism and
      propylthiouracil (PTU)-induced agranulocytosis are presented. The first patient,
      age 47, received 300 mg of PTU per day and developed agranulocytosis within 6
      weeks of the commencement of therapy. There were no granulocytes in the
      peripheral smear and a bone marrow biopsy demonstrated an absence of the entire
      myeloid cell line as well as the presence of many granulomas. The second patient,
      age 39, received PTU 1600 mg per day for two and half weeks and then 2 days of
      methimazole, 200 mg per day. She developed complete agranulocytosis on peripheral
      smear within 3 weeks of the initiation of therapy. Her bone marrow biopsy
      demonstrated maturation arrest of the granulocytic cell line at the myelocyte
      stage. In addition to discontinuing their antithyroid drugs, both patients were
      treated with G-CSF subcutaneously. The first patient received 300 micrograms of G
      CSF on days 2 and 4 after discontinuing PTU with the appearance of 4.7 x 10(9)/L
      granulocytes and granulocyte precursors on day 4. The second patient received 575
      micrograms of G-CSF for 2 days and 300 micrograms for 1 additional day beginning
      on the third day after discontinuing antithyroid drugs. On the second treatment
      day there were 5.8 x 10(9)/L granulocytes and granulocyte precursors on the
      peripheral smear. A comparison to previously published cases on antithyroid drug
      induced agranulocytosis suggests that the use of G-CSF decreased the amount of
      time required for marrow recovery after the cessation of the offending drug.

PMID- 7509670
TI  - Thyrotropin receptor autoantibodies recognizing two different epitopes on the TSH
      receptor: lack of relationship to patient age, sex, and ophthalmopathy.
AB  - The existence of two populations of stimulatory TSH receptor autoantibodies
      against different epitopes raises the possibility of a link between one type of
      autoantibody and the clinical manifestations of Graves' disease. To test this
      hypothesis, serum immunoglobulins from 48 patients with Graves' disease were
      assayed for TSH binding inhibition (TBI) activity with two different recombinant
      TSH receptor variants (TSH-LHR-6 and TSH-LHR-6-A1) expressed on Chinese hamster
      ovary cells. The activity of 27 of the 48 patients' immunoglobulin samples was
      significantly less (difference in TBI value of 9% or greater) with chimera 6-A1
      than with chimera 6. No immunoglobulin sample had significantly greater TSH
      binding inhibitory activity with chimera 6-A1 than with chimera 6. Sensitivity to
      the 6-A1 epitope substitution did not correlate with patient age, sex, or the
      presence or absence of hyperthyroidism. Further, there was no segregation of
      individual patients with TSH receptor autoantibodies with 6-A1 epitope
      sensitivity in terms of the past or present occurrence of ophthalmopathy,
      including the severity (total eye score), clinical activity, duration, and type
      of therapy. These data indicate that recognition by autoantibodies of the 6-A1
      epitope on the TSH receptor is not associated with the ophthalmopathy of Graves'
      disease. However, the possibility cannot be excluded that other functional (or
      even nonfunctional receptor autoantibodies that are not detectable by present
      assays) may still play a role in the pathogenesis of Graves' ophthalmopathy.

PMID- 7509673
TI  - Has the use of antithyroid drugs for Graves' disease become obsolete?
AB  - In spite of an experience of almost 50 years of use of antithyroid drugs and
      radioiodine for the treatment of Graves' disease, the rationale for choice is
      often obscure. Early reports of high remission rates during thiourea therapy were
      followed by less optimistic ones, which along with other factors may have fueled
      the current major shift toward use of radioiodine. This review examines whether
      or not the use of antithyroid drugs indeed may have become obsolete. The
      intrathyroidal and extrathyroidal mechanisms of action of the drugs are reviewed
      with emphasis on their potential immunosuppressive effects. The latter may
      involve a direct effect on thyroid follicular cells, a direct suppression of TSH
      receptor antibody formation, or indirect effects mediated via heat shock
      proteins, oxygen free radicals, and the immune system. Potential factors
      associated with success or failure with antithyroid drug therapy are discussed,
      such as the effects of dose and duration of treatment, iodine milieu, and
      concomitant L-thyroxine therapy. The risks inherent to radioiodine therapy are
      only briefly described with emphasis on the possible aggravation by radioiodine
      of preexistent ophthalmopathy. The reader must decide whether the evidence
      marshalled convincingly indicates that the use of the thiourea compounds should
      be abandoned. The author thinks not, and is optimistic that imminent discovery of
      the yet elusive and enigmatic pathogenesis of Graves' disease will permit new and
      innovative treatment or more effective use of currently available therapies.

PMID- 7509674
TI  - [Significance of vasomotor reactions for gynecologic oncologic therapy].

PMID- 7509675
TI  - [Initial experiences with the triple test in Austria].

PMID- 7509676
TI  - [High-dose epirubicin in combination with high-dose ifosfamide plus granulocyte
      colony stimulating factor in patients with advanced platin-pretreated ovarian
      cancer. Phase I-II study].

PMID- 7509677
TI  - [Use of G-CSF in dose-intensified chemotherapy of breast cancer with FEC
      (500/75/500 mg/m2 KO) in the adjuvant and metastatic situation].

PMID- 7509678
TI  - [Ionic stretch-dependent channels in the urogenital tract. Pharmaco-physiology of
      tocolysis].

PMID- 7509679
TI  - Photochemical sterilization of 3SR reactions.
AB  - The self-sustained sequence replication (3SR) reaction is an extremely efficient
      method for amplifying target DNA and RNA sequences that may be present in minute
      quantities. A serious problem often encountered in its practice is carryover
      contamination from products of previous 3SR reactions. A postamplification
      treatment of 3SR reaction products with the photoactive agent 4'-aminomethyl-4,5
      dimethylisopsoralen (IP-10) was investigated as an approach for preventing
      carryover contamination by 3SR amplicons. Initially, inhibition of the
      amplification reaction by high concentrations of the reagent was observed. This
      problem was circumvented by developing a gel-based delivery of IP-10, and the
      method was found to provide highly efficient sterilization (approximately 10(6)
      fold) of 3SR amplicons. Evaluation of this strategy on a number of 3SR targets
      has indicated that the degree of sterilization is dependent on the length of the
      amplified region and on the concentration of IP-10. It appears that the
      sterilization effect is caused by covalent modification of the pyrimidine bases
      of RNA and DNA, which renders them unusable as templates for the 3SR reaction.
      Modification of a purified RNA transcript with IP-10 was shown to prevent
      effectively reverse transcription by avian myeloblastosis virus reverse
      transcriptase (AMV RT). Similarly, treatment of a T7 RNA polymerase promoter
      containing DNA template with IP-10 eliminated full-length transcription by T7 RNA
      polymerase. This isopsoralen method may be used to sterilize multiple 3SR
      reactions in a clinical assay with a convenient UV irradiation step.

PMID- 7509680
TI  - PCR-mediated detection of heteroplasmy in maize mitochondrial mutants.

PMID- 7509681
TI  - Effect of oestradiol on the carbohydrate metabolism of immature rat uterus: the
      role of fructose-2, 6-bis-phosphate and of phosphoribosyl pyrophosphate.
AB  - Enzymes and metabolic intermediates of glycolysis, pentose phosphate pathway and
      the tricarboxylic acid cycle were measured in immature rat uterus after treatment
      with oestradiol. The flux of glucose through alternative pathways was examined.
      Fructose-2,6-bis-phosphate, the well known regulator of glycolytic pathway,
      increased after the injection of oestradiol and remained elevated. This increase
      was accompanied by raised levels of most of glycolytic intermediates and by
      increase in glycolytic flux. The key enzymes of glycolysis and all the enzymes of
      pentose phosphate pathway showed a gradual increase in the activity with
      administration of oestradiol up to 48 hours. Phosphoribosyl pyrophosphate, the
      metabolite required in nucleotide synthesis, was also elevated. Marked changes in
      the levels of key metabolic intermediates and the enzyme activities are
      correlated with the increased nucleic acid, protein and lipid synthesis occurring
      following oestradiol treatment.

PMID- 7509682
TI  - Structural characterization of gelonin: evidence for separate antigenic and
      cytotoxic domains.
AB  - The N-terminal sequence of the three isoforms of gelonin is identical. Cyanogen
      bromide cleavage of gelonin produced fragments of Mr 17,000, 13,000, 11,000 and
      7,000. The apparent Mr 17,000 component was identified as the N-terminal fragment
      and represents the major antigenic domain of the protein as it reacted with
      antibody to the native protein but this fragment did not inhibit protein
      synthesis in the in vitro translation assay. Our data may suggest possibilities
      for separation of antigenic and catalytic domains of this ribosome inactivating
      protein.

PMID- 7509683
TI  - Three novel mutations (I506S, S466X, 1651A-->T) in exon 10 of the cystic fibrosis
      transmembrane conductance regulator (CFTR) detected in patients of southern
      German descent.

PMID- 7509684
TI  - Identification of a novel missense mutation (G314E) in exon 7 of the cystic
      fibrosis transmembrane conductance regulator gene identified in a CF patient with
      pancreatic sufficiency.

PMID- 7509686
TI  - Management of cancer pain: adults. Agency for Health Care Policy and Research.
AB  - This Quick Reference Guide for Clinicians contains highlights from the Clinical
      Practice Guideline on Management of Cancer Pain, which was developed by a private
      sector panel of health care providers and consumers. Selected aspects of
      evaluating and managing pain in adults with cancer pain are presented. Topics
      covered include initial assessment, pharmacologic treatment, administration of
      medications, side effects of medications, adjuvant medications, cognitive
      behavioral interventions, and discussion of other more invasive palliative
      techniques. A flowchart is included that shows the sequence of events in
      evaluating and managing cancer pain, as well as drug dosing tables and forms to
      assist the clinician and patient to adequately describe and assess pain.

PMID- 7509685
TI  - Identification of a new frameshift mutation (3724 delG) in exon 19 of the CFTR
      gene.

PMID- 7509687
TI  - Potentiating effect of Bay K 8644 on agonist-induced ileal contractions.
AB  - The effects of Bay K 8644 on agonist-induced ileal contractions were
      investigated. Histamine, serotonin and a acetylcholine (10(-8)-10(-4) M) produced
      a dose-dependent contraction. Maximum contraction was obtained by 10(-5) M
      serotonin. Its value was 1076 mg. Bay K 8644 (10(-6) M) increased the potency of
      histamine and serotonin-induced ileal contractions, but acetylcholine induced
      responses were not increased. All responses of agonists were inhibited by
      nifedipine (10(-6) M). This inhibition was decreased with increasing
      acetylcholine concentrations. These results suggest that histamine and serotonin
      induced/mediated contractions in guinea-pig ileum are independent of calcium
      influx through voltage operated channels.

PMID- 7509688
TI  - Palliative ventilatory support: use of noninvasive positive pressure ventilation
      in terminal respiratory insufficiency.

PMID- 7509689
TI  - About nonradioactive nucleic acid detection.

PMID- 7509690
TI  - Southern blot hybridization of digoxigenin-labeled RNA minisatellite probes and
      color detection.

PMID- 7509691
TI  - Hybridization and detection of digoxigenin probes on RNA blots.

PMID- 7509693
TI  - Detection of digoxigenin-labeled DNA probes hybridized to plant chromosomes in
      situ.

PMID- 7509692
TI  - Direct fluorochrome-labeled DNA probes for direct fluorescent in situ
      hybridization to chromosomes.

PMID- 7509694
TI  - PACE (Probe Assay--Chemiluminescence Enhanced). A magnetic bead assay for the
      noncultural diagnosis of gonorrhea.

PMID- 7509695
TI  - Nucleic acid sequence-based amplification (NASBA).

PMID- 7509696
TI  - Isolation of plant RNA.

PMID- 7509698
TI  - Preparation of RNA gel blots.

PMID- 7509699
TI  - Preparation of RNA dot blots.

PMID- 7509701
TI  - Serum concentrations of alpha-fetoprotein in children with primary
      hypothyroidism.

PMID- 7509697
TI  - Isolation of total and poly A+ RNA from animal cells.

PMID- 7509703
TI  - Quantification of cell loss during bronchoalveolar lavage fluid processing.
      Effects of fixation and staining methods.
AB  - Discrepancies have been reported in differential cell counts according to the
      diverse processing methods used in bronchoalveolar lavage (BAL) fluid management.
      The differences have proved to be mainly the result of selective lymphocyte loss,
      while the exact mechanisms of the phenomenon remain controversial. Observing a
      similar variation in differentials from differently stained identical smears, we
      quantified the cell loss due to staining procedures from 45 consecutive
      satisfactory BAL procedures. To do this, we compared relative lymphocyte recovery
      on neat pooled lavage in a hemocytometer with that from smears and cytopreps
      fixed and stained in different ways. We found (1) A significant lymphocyte loss
      (p < 0.05) whatever the staining method. (2) Different methods of fixation and
      staining lead to considerable variation in differentials from slides otherwise
      identically managed. The loss is higher during air-drying fixation followed by
      staining with an aqueous medium such as Diff-Quik than on spray-fixed slides
      stained in an alcohol medium such as Papanicolaou stain. (3) The effect of
      lymphocyte loss on differentials is more important when the initial lymphocytosis
      is less than 35%, and decreases to nonsignificance when it exceeds 70%. The role
      of cytocentrifugation or other manipulations in cell loss probably has been
      overestimated because unknown effects of staining methods were also attributed to
      these manipulations. We suggest that lymphocyte loss could arise from poor
      adherence on slides, which is exacerbated during aqueous staining if no artifice
      (e.g., spray fixation), is used to hold them. Thus, the definition of the long
      awaited standard procedure for an accurate differential count of BAL fluid must
      take into account fixation and staining methods.

PMID- 7509702
TI  - The bidirectional Glenn procedure: palliation of the univentricular heart.

PMID- 7509700
TI  - Digoxigenin labeling of RNA transcripts from multi- and single-locus DNA
      minisatellite probes.

PMID- 7509704
TI  - Bradykinin-induced airway inflammation. Contribution of sensory neuropeptides
      differs according to airway site.
AB  - We examined the mechanisms of bradykinin-induced airway microvascular leakage in
      guinea pig airways by measuring extravasation of Evans blue dye. Animals were
      pretreated with propranolol (1 mg/kg, intravenous) and atropine (1 mg/kg,
      intravenous) to block the beta-adrenergic and muscarinic responses, respectively.
      Bradykinin (250 nmol) instillation into airways significantly increased the
      leakage of dye in the trachea, main bronchi, and intrapulmonary airways to the
      same degree. The bradykinin B2-receptor antagonist HOE140 (500 nmol/kg,
      intravenous) did not alter basal leakage but almost completely inhibited
      bradykinin-mediated leakage. By contrast, the neurokinin NK1 antagonist FK888 (10
      mg/kg, intravenous) partially inhibited bradykinin-induced leakage in trachea (p
      < 0.01) and main bronchi (p < 0.01), but had no significant effect on
      intrapulmonary airways. Indomethacin (5 mg/kg, intravenous) had no effect on the
      plasma leakage after instilled bradykinin. We concluded that the airway
      inflammatory response to bradykinin administered directly into the airways is
      mediated by bradykinin B2 receptors and partially mediated by tachykinin release
      from sensory nerve terminals, whereas cyclooxygenase products have no important
      role in the response. In the central airways, the contribution of sensory
      neuropeptides to the bradykinin response is greater than that caused by direct
      stimulation of the B2 receptor on the endothelium at the postcapillary venule of
      the bronchial circulation. In contrast, in the peripheral airways, the
      contribution of direct B2-receptor stimulation on the airway vasculature is
      greater than that involving sensory neuropeptides.

PMID- 7509705
TI  - Upregulation of adhesion molecules in the bronchial mucosa of subjects with
      chronic obstructive bronchitis.
AB  - To determine whether adhesion molecules and cytokines are upregulated in the
      bronchial mucosa of chronic bronchitics, we obtained bronchial biopsies in 16
      chronic bronchitics, in eight asymptomatic smokers, and in seven normal
      nonsmoking subjects. Bronchial biopsies were examined by immunohistochemistry to
      identify the expression of E-selectin and intercellular adhesion molecular-1
      (ICAM-1) on vessels and on bronchial epithelium, and the expression of
      interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha),
      neutrophil elastase, and eosinophil cationic protein (EG-2) on cells in the
      submucosa. Chronic bronchitics had an increased number of E-selectin-positive
      vessels when compared with both asymptomatic smokers (p < 0.05) and normal
      subjects (p < 0.01). The numbers of ICAM-1-positive vessels, neutrophils, and IL
      1 beta, TNF-alpha-, and EG-2-positive cells were not significantly different in
      the three groups of subjects examined. When the bronchitic group was divided
      according to the presence or absence of airway obstruction, the increased number
      of E-selectin-positive vessels persisted only in bronchitics with airway
      obstruction, who also had an increased expression of ICAM-1 on basal epithelial
      cells. We concluded that in the bronchial mucosa of chronic bronchitics with
      airway obstruction, there is an increased expression of E-selectin on vessels and
      of ICAM-1 on basal epithelial cells, suggesting the involvement of these adhesion
      molecules in the pathogenesis of the disease.

PMID- 7509706
TI  - The American-European Consensus Conference on ARDS. Definitions, mechanisms,
      relevant outcomes, and clinical trial coordination.
AB  - The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic
      pulmonary edema and hypoxemia associated with a variety of etiologies, carries a
      high morbidity, mortality (10 to 90%), and financial cost. The reported annual
      incidence in the United States is 150,000 cases, but this figure has been
      challenged, and it may be different in Europe. Part of the reason for these
      uncertainties are the heterogeneity of diseases underlying ARDS and the lack of
      uniform definitions for ARDS. Thus, those who wish to know the true incidence and
      outcome of this clinical syndrome are stymied. The American-European Consensus
      Committee on ARDS was formed to focus on these issues and on the pathophysiologic
      mechanisms of the process. It was felt that international coordination between
      North America and Europe in clinical studies of ARDS was becoming increasingly
      important in order to address the recent plethora of potential therapeutic agents
      for the prevention and treatment of ARDS.

PMID- 7509707
TI  - Activation of alpha-adrenoceptors indirectly facilitates sodium pumping in frog
      motoneurons.
AB  - The effects of clonidine on Na+ pumping in motoneurons of the isolated frog
      spinal cord was investigated using sucrose gap recordings from ventral roots. Na+
      pump activity, induced in motoneurons either by tetanizing the dorsal root or by
      rapidly exposing the cord to normal medium following 30 min in K(+)-free Ringer's
      solution (K(+)-activated hyperpolarizations), was increased by application of
      clonidine (100 microM). These actions of clonidine were blocked by the
      preferential alpha 2-adrenergic antagonist yohimbine, but not by alpha 1
      adrenergic antagonist prazosin or the beta-blocker propranolol. Clonidine's
      effects on Na+ pumping appeared to be indirect (presumably via interneurons)
      because its effects on K(+)-activated hyperpolarizations were reduced by
      tetrodotoxin (TTX) or high concentrations of Mg2+. This indirect mechanism
      involved activation of non-NMDA excitatory amino acid receptors. Thus, in the
      presence of clonidine, CNQX, but not APH, limited the ability of clonidine to
      enhance K(+)-activated hyperpolarizations. The AMPA receptor may play a role in
      the process, K(+)-activated hyperpolarizations were augmented by the presence of
      AMPA; NMDA had no effect. The present results are consistent with the idea that
      activation of alpha 2-adrenoceptors produces the following: the release of
      excitatory amino acids from interneurons; the activation of non-NMDA receptors on
      motoneurons; increased Na+ influx and loading and increased Na+ pump activity.

PMID- 7509708
TI  - Diminished effect of inhibition of nitric oxide synthase on regional cerebral
      vascular resistance in conscious and in isoflurane anesthetized rats during
      hemorrhage.
AB  - Effects of a nitric oxide (NO) synthase inhibitor on regional cerebral vascular
      resistance (rCVR) and regional cerebral blood flow (rCBF) were studied during a
      severe hemorrhage in conscious and in isoflurane anesthetized groups of rats.
      Half of each group was infused with NG-nitro-L-arginine-methyl ester (L-NAME), a
      NO synthase inhibitor, at a rate of 2 mg.kg-1.min-1 for 30 min. Half of the L
      NAME infused and half of the normal saline infused rats were bled to reduce the
      mean arterial blood pressure (MAP) to 44-49 mmHg. rCBF was measured using
      [14C]iodoantipyrine. rCVR was calculated as the ratio of MAP to rCBF. In the
      conscious non-hemorrhagic rats, L-NAME markedly increased rCVR in all the brain
      regions that we studied. In the conscious rats without L-NAME treatment,
      hemorrhage decreased rCVR in most of the brain regions. With L-NAME treatment in
      this group, hemorrhage increased rCVR only in the rostral part of the brain.
      Isoflurane decreased rCVR in most of the brain regions except the cortical area.
      L-NAME markedly increased rCVR in all the brain regions that we studied in the
      isoflurane anesthetized rats. In the isoflurane anesthetized rats, hemorrhage did
      not reduce rCVR in any of the brain regions. In the isoflurane anesthetized
      hemorrhagic rats, L-NAME did not significantly affect rCVR in any of the brain
      regions that we studied. We found that L-NAME increased rCVR to a greater extent
      in the non-hemorrhagic rats than in the hemorrhagic rats in both the conscious
      and in the isoflurane anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509710
TI  - Evidence that L-type calcium channels do not contribute to static vestibular
      function in the guinea pig vestibular nucleus.
AB  - Labyrinthine-intact guinea pigs received unilateral, brainstem cannula injections
      of (1) 2.5 micrograms of the selective dihydropyridine L-type Ca2+ channel
      agonist, Bay K 8644 (n = 4 animals); (2) 10 micrograms Bay K 8644 (n = 4); 12.5
      micrograms of the selective dihydropyridine L-type Ca2+ channel antagonist,
      nifedipine (n = 4); or 40 micrograms nifedipine (n = 4). In 11/16 cases, the
      lesion associated with the cannula tip was located within or near the border of
      the right vestibular nucleus (VN) complex. All cannula injections were delivered
      in a 1 microliter volume of artificial cerebrospinal fluid (ACSF) and
      dimethylsulphoxide (DMSO) (70% DMSO, 30% ACSF for Bay K 8644; 80% DMSO, 20% ACSF
      for nifedipine), adjusted to a pH of approx. 7.0. The effects of these injections
      were compared with control injections of ACSF/DMSO in our previous studies.
      Animals were observed for signs of a labyrinthine syndrome (i.e. spontaneous
      ocular nystagmus, yaw and roll head tilt) directed to the contralateral or
      ipsilateral side. In no case did Bay K 8644 or nifedipine cause ocular motor or
      postural symptoms similar to those produced by a unilateral labyrinthectomy.
      These results suggest that L-type Ca2+ channels do not contribute significantly
      to the resting activity of VN neurons and therefore do not contribute to static
      vestibular function at the level of the VN.

PMID- 7509709
TI  - Regulation of the prefrontal cortical dopamine release by GABAA and GABAB
      receptor agonists and antagonists.
AB  - The gamma-aminobutyric acid-dopamine (GABA-DA) relationship was studied by
      intracerebral microdialysis in the prefrontal cortex. Nomifensine (5 microM) was
      included in the Ringer solution during all the dialysis experiments. Muscimol, a
      GABAA receptor agonist (50 and 500 microM) did not affect the extracellular
      output of DA and 3,4-dihydroxyphenylacetic acid (DOPAC). Baclofen, a GABAB
      receptor agonist (50 microM) significantly decreased the extracellular output of
      DA and DOPAC. On the other hand, picrotoxin and phaclofen, GABAA and GABAB
      receptor antagonists respectively, at a concentration of 50 microM, both
      significantly increased the release of DA. While the DOPAC level was affected
      only by picrotoxin perfusion. The present study indicates that GABA could control
      the release of DA in the prefrontal cortex.

PMID- 7509711
TI  - The lateral hypothalamus: a primary site mediating excitatory amino acid-elicited
      eating.
AB  - Lateral hypothalamic (LH) injections of the excitatory neurotransmitter
      glutamate, or its excitatory amino acid (EAA) agonists, kainic acid (KA), D,L
      alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA), or N-methyl-D
      aspartic acid (NMDA), can rapidly elicit an intense feeding response in satiated
      rats. To determine whether the LH is the actual locus of this effect, we compared
      these compounds' ability to stimulate feeding when injected into the LH, versus
      when injected into sites bracketing this region. Food intake in groups of adult
      male rats was measured 1 h after injection of glutamate (30-900 nmol), KA (0.1
      1.0 nmol), AMPA (0.33-3.3 nmol), NMDA (0.33-33.3 nmol) or vehicle, through
      chronically implanted guide cannulas, into one of seven brain sites. These sites
      were: the LH, the anterior and posterior tips of the LH, the thalamus immediately
      dorsal to the LH, the amygdala just lateral to the LH, or the paraventricular and
      perifornical areas medial to the LH. The results show that across doses and
      agonists the eating-stimulatory effects were largest with injections into the LH.
      In the LH, glutamate between 300 and 900 nmol elicited a dose-dependent eating
      response of up to 5 g within 1 h (P < 0.01). Each of the other agonists at doses
      of 3.3 nmol or less elicited eating responses of at least 10 g with injections
      into this site. Injections into the other brain sites produced either no eating,
      or occasionally smaller and less consistent eating responses.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7509712
TI  - Differential alterations of ion channel binding sites in temporal and occipital
      regions of the cerebral cortex in Alzheimer's disease.
AB  - Three ion channel binding sites were examined by means of quantitative ligand
      binding autoradiography in temporal and occipital cortex from 9 patients with
      neuropathologically confirmed Alzheimer's disease (AD) and 7 matched control
      subjects. The following ligands were used: 125I-apamin to label a population of
      Ca(2+)-sensitive K+ channels; [3H]PN200-110 to label L-type voltage-sensitive
      Ca2+ channels and [3H]glibenclamide to label ATP-sensitive K+ channels. Ion
      channel binding sites were compared to: choline acetyltransferase (ChAT) activity
      and plaque densities measured in the same tissue. In the temporal cortex in AD
      125I-apamin binding was increased compared to controls (e.g. superficial layers:
      control = 0.71 +/- 0.07; AD = 1.02 +/- 0.07, mean +/- S.E.M. pmol/g tissue). In
      contrast, in adjacent sections [3H]glibenclamide binding was reduced in AD
      compared to controls (e.g. superficial layers: control = 25.3 +/- 1.7; AD = 17.9
      +/- 1.4 pmol/g tissue). [3H]PN200-110 binding in temporal cortex was not altered
      in AD compared to controls. In the occipital cortex 125I-apamin binding was
      increased in AD while both [3H]glibenclamide and [3H]PN-200-110 binding sites in
      this cortical area were not different from controls. Plaque density (per mm2) was
      higher in temporal (e.g. layers I-III, 43 +/- 6) than in occipital cortex (layers
      I-III, 27 +/- 4) in the AD patients while ChAT activity was reduced by 40% in
      temporal cortex and by 50% in occipital cortex compared to controls. The results
      suggest that the three ion channel binding sites are located on structural
      elements in the brain which are differentially affected by the pathophysiology of
      AD.

PMID- 7509713
TI  - Different subsets of CNS neurons express different glycosaminoglycan epitopes on
      large perineuronal proteoglycans.
AB  - Proteoglycans are known to occur in the central nervous tissue, but their
      function is not well understood. We made a biochemical study of four perineuronal
      antigens on different subsets of rat brain neurons and found that three antigens
      recognized by antibodies against glycosaminoglycan epitopes were large
      proteoglycans. Molecular masses estimated by immunoblotting were 700 kDa for 473,
      376 and 1B5 antigens and 600 kDa for the 374 antigen. Reactivities of the
      antigens on immunoblots to monoclonal antibodies (MAbs) 473 and 376 were lost,
      and that to MAb 1B5 uncovered, after chondroitinase ABC treatment as in the brain
      sections. The elution profiles from ion-exchange and gel-filtration column
      chromatography of 473, 376 and 1B5 antigens were quite similar, but those of 374
      antigen were slightly different. The immunoaffinity-purified 473 antigen migrated
      at 700 kDa on sodium dodecylsulfate gel electrophoresis, and chondroitinase ABC
      treatment decreased the molecular mass to 600 kDa. The 473 antigen was recognized
      by MAbs 376 and 1B5 although these MAbs also reacted with 473-negative 700 kDa
      molecules. These results suggest that neuronal subset-specific glycosylation may
      occur on the 700 kDa proteoglycans, and that the glycosaminoglycan structures may
      be involved in the pericellular diversity of CNS neurons.

PMID- 7509714
TI  - Effect of changes in rate of vascular perfusion on release of substances into the
      effluent from the brain of the rabbit.
AB  - The cerebral vasculature of five anaesthetised rabbits was perfused with a
      perfluorocarbon emulsion via the internal carotid arteries, and the effluent from
      the jugular veins analysed for ATP, substance P (SP), endothelin (ET) and
      arginine vasopressin (AVP). Viability of the preparation was monitored
      periodically by the electrocorticogram, oxygen uptake, carbon dioxide release and
      perfusion pressure. The basal rate of infusion of 7.8 +/- 1.26 ml.min-1 resulted
      in an infusion pressure of 114.0 +/- 22.1 mmHg and when increased first to 10.5
      +/- 1.53 ml.min-1 and then to 15.0 +/- 1.87 ml.min-1, rose to 163.0 +/- 33.1 mmHg
      and to 170.0 +/- 33.2 mmHg, respectively. Between each 3-min period of increased
      flow the rate was returned to the basal rate for 6 min. Of the four vasoactive
      substances, ET was released at the largest rate during the initial period of
      basal flow, 65.3 +/- 10.7 pmol.min-1. This increased further when the infusion
      rate rose to 10.5 ml.min-1, but was significant only when the infusion rate was
      increased to 15.0 ml.min-1. ATP was released at 41.5 +/- 11.5 pmol.min-1 during
      the initial period of basal flow. Its release significantly increased with flow
      and peaked at 15.0 ml.min-1. SP was released at a rate of 13.3 +/- 8.2 pmol.min-1
      during the initial period of basal flow. Its rate of release was increased
      significantly the second time the flow was increased to 10.5 ml.min-1 and
      increased even further when the flow was increased to 15.0 ml.min-1.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7509716
TI  - Pathophysiological and clinical aspects of immediate hypersensitivity to latex.

PMID- 7509718
TI  - Nitric oxide synthase activity in human gynecological cancer.
AB  - Nitric oxide is generated by the NO synthases, a family of isoenzymes expressed
      in a wide range of mammalian cells. In the vascular and nervous systems distinct
      isoforms generate NO to act as a signal transduction mechanism. The isoform
      induced by cytokines, on the other hand, provides a sustained release of NO which
      mediates some cytotoxic and cytostatic effects of the immune system. Solid tumors
      are a heterogeneous population of cell types, including tumor, vascular, and
      infiltrating immune cells. Studies in vitro show that NO synthase can be present
      in many of these cells. However, its presence in situ in solid human tumors has
      not been reported. In this study, we have investigated NO synthase activity and
      its cellular localization in malignant and nonmalignant human gynecological
      tissue. Nitric oxide synthase activity was observed in malignant tissue, was
      highest (> or = 250 pmol/min/g tissue) in poorly differentiated tumors, and was
      below detectable levels in normal gynecological tissue. Furthermore,
      investigations with a polyclonal NO synthase antibody revealed immunoreactivity
      only in malignant tissue. This was associated with NO synthase activity and
      localized to tumor cells. Thus NO synthase is present in human gynecological
      tumors, and its presence seems to correlate inversely with the differentiation of
      the tumor.

PMID- 7509715
TI  - Radiographic features of hepatocellular carcinoma and their relation to prognosis
      in Canada.
AB  - To determine the radiographic features of hepatocellular carcinoma (HCC) as seen
      in Canada and their relation to prognosis, multiple imaging studies for 40
      patients with histologically proven HCC were reviewed. The patients, 34 men and 6
      women ranging in age from 43 to 86 years, were selected from a larger database on
      the basis of the availability of ultrasound (US) images and at least one other
      imaging study. The patients had been examined between 1981 and 1991 at a tertiary
      care hospital. In 35 of the 40 cases (88%) HCC had been detected by US
      assessment, the criterion for complete analysis, but in one of those cases the
      lesion was not observed in the initial scans. HCC was detected by computed
      tomography (CT) in the 27 cases in which that technique had been used. Cirrhosis
      was present in 27 of the 35 patients (77%) for which a complete analysis was
      performed. Median survival after diagnosis for all 40 patients was 14.1 weeks.
      Seven radiographic features were analysed for prognostic value by univariate and
      multivariate (Cox) regression analysis. However, the regression analysis
      indicated no relation between survival and tumour size, the nature of the tumour
      (diffuse and infiltrative or discrete), vascular involvement, encapsulation,
      extrahepatic spread, tumour location or echogenicity. No radiographic feature,
      including tumour size, correlated with the serum level of alpha-fetoprotein,
      which was elevated in 23 of the 32 cases (72%) in which it had been determined.
      These results confirm the variable radiographic appearance of HCC but differ in
      other respects from those reported previously, particularly those for studies
      performed outside North America.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509717
TI  - Ornithine decarboxylase expression in cutaneous papillomas in SENCAR mice is
      associated with altered expression of keratins 1 and 10.
AB  - The patterns of expression of ornithine decarboxylase (ODC) and a number of
      keratinocyte differentiation products were examined in early papillomas by
      immunocytochemistry as an initial effort to develop phenotypic markers of the
      early stages of mouse skin tumorigenesis. Tumors were induced in SENCAR mice by
      initiation with 7,12-dimethylbenzanthracene, followed by once or twice weekly
      promotion treatments with 12-O-tetradecanoylphorbol-13-acetate. The patterns of
      immunocytochemical staining observed in early papillomas, collected after 7 weeks
      of promotion, were compared to those obtained with control skin and large,
      hyperkeratotic papillomas, collected after 23 weeks of promotion. In groups
      receiving 12-O-tetradecanoylphorbol-13-acetate, constitutive and induced ODC
      expression were evaluated either several days or 4.5 h after the last treatment,
      respectively. The major differentiation products in suprabasal keratinocytes are
      keratins, K1 and K10. These keratins were normally expressed in mildly
      hyperplastic epidermis, but staining became patchy in markedly hyperplastic
      epidermis. In early papillomas, K1 staining was patchy, and K10 staining occurred
      in very limited focal areas or was negative, such that the absence of staining
      delineated the lesions. Antibodies to the basal cell keratins, K5 and K14,
      stained both basal and suprabasal cells in hyperplastic epidermis and papillomas.
      Similarly, an antibody to keratin K6, which is expressed under conditions of
      hyperproliferation, uniformly stained the basal and suprabasal layers of
      hyperplastic epidermis and papillomas, demonstrating that the staining patterns
      observed with the antibodies to K1 and K10 were specific. Expression of ODC in
      the histologically normal skin of control mice was detected only in the hair
      follicles and depended on the hair cycle. Staining for induced ODC in mice
      treated with 12-O-tetradecanoylphorbol-13-acetate once weekly for 7 weeks was
      intense and diffuse throughout the suprabasal layers of the epidermis. In early
      and large papillomas, staining for constitutively expressed ODC was intense and
      diffuse in suprabasal cells. This intense staining for ODC occurred consistently
      in areas with decreased K1 and K10 expression, and, therefore, was associated
      with an altered pattern of differentiation. High constitutive ODC expression and
      decreased K1 and K10 expression will be useful phenotypic markers for studying
      the early stages of tumorigenesis in mouse skin.

PMID- 7509719
TI  - Expression of multidrug resistance gene and localization of P-glycoprotein in
      human primary ovarian cancer.
AB  - Resistance to chemotherapy is the major obstacle to controlling malignant tumors.
      To characterize multidrug resistance phenotype in human primary ovarian cancer
      without chemotherapy, expressions of the mdr1 gene in 52 cases of ovarian cancer
      (44 common epithelial, 5 nonepithelial, and 3 metastatic cancers) were analyzed
      by polymerase chain reaction of RNA after reverse transcription. Furthermore,
      localization of P-glycoprotein, which is encoded by the mdr1 gene, was studied
      immunohistochemically. Although overall expression of the mdr1 gene was
      relatively low, its expression level was the highest in well-differentiated
      cancer tissues. Serous and mucinous adenocarcinomas showed higher levels of
      expression compared with clear cell and endometrioid carcinomas. P-glycoprotein
      was positive on luminal surfaces of lining cells of ovarian cancer and on those
      of inclusion cysts from which epithelial ovarian cancer is considered to develop.
      Thus, some ovarian cancer cases before chemotherapy are intrinsically multidrug
      resistant, which can be determined by mdr1 gene expression, and this phenotype
      should be taken into account for effective chemotherapy of ovarian epithelial
      carcinomas.

PMID- 7509720
TI  - Expression of CD44 in human lung tumors.
AB  - CD44 is an integral membrane glycoprotein that functions as a receptor for the
      extracellular matrix glycan, hyaluronan. Here we report that CD44 is a novel
      biomarker for non-small cell lung tumors, squamous metaplasia of the lung, and
      activated type II pneumocytes. We have examined the expression of CD44 in 12
      human lung tumor cell lines and 23 fixed, paraffin-embedded lung cancers. CD44
      transcription and translation is consistently high among non-small cell tumors (5
      of 5 cell lines, 10 of 14 tumors) but rare in small cell tumors (1 of 6 cell
      lines, 0 of 9 tumors). In normal lung, CD44 was confined to the surface of
      bronchial basal cells and alveolar macrophages. Squamous metaplasia of the lung
      showed strong CD44 immunoreactivity. Resting type II pneumocytes were largely
      CD44 negative but rows of active, surfactant-secreting type II cells had
      significant amounts of CD44 located on lateral surfaces of adjacent cells. The
      correlation between CD44 and the non-small cell phenotype was further
      demonstrated in studies of a cultured small cell lung cancer line induced to
      exhibit characteristics of a non-small lung cancer by infection with v-Ha-ras.
      Following ras gen insertion, these cells showed a 40-fold increase in CD44
      expression. The CD44 detected in lung cancer cells throughout these studies was
      predominantly the "standard" rather than the "variant" species. Taken together,
      these results suggest that CD44 is a protein expressed on non-small cell lung
      tumors, squamous metaplasia, and activated type II cells. In addition, CD44 in
      cultured small cell lung cancer cells is transcriptionally activated following
      differentiation by the ras oncogene. The fact that immunohistochemistry can be
      used to discriminate among the cell types makes CD44 a valuable new marker for
      lung neoplasia.

PMID- 7509721
TI  - Vagal innervation of the rat pylorus: an anterograde tracing study using
      carbocyanine dyes and laser scanning confocal microscopy.
AB  - In an attempt to identify the distribution and structure of vagal fibers and
      terminals in the gastroduodenal junction, vagal efferents were labeled in vivo by
      multiple injections of the fluorescent carbocyanine dye DiA into the dorsal motor
      nucleus (dmnX), and vagal afferents were anterogradely labeled by injections of
      DiI into the nodose ganglia of the same or separate rats. Thick frontal cryostat
      sections were analysed either with conventional or laser scanning confocal
      microscopy, using appropriate filter combinations and/or different wavelength
      laser excitation to distinguish the fluorescent tracers. Vagal efferent terminal
      like structures were present in small ganglia within the circular sphincter
      muscle, which, in the absence of a well-developed, true myenteric plexus at this
      level, represent the myenteric ganglia. Furthermore, vagal efferent terminals
      were also present in submucosal ganglia, but were absent from mucosa, Brunner's
      glands and circular muscle fibers. Vagal afferent fibers and terminal-like
      structures were more abundant than efferents. The most prominent afferent
      terminals were profusely branching, large net-like aggregates of varicose fibers
      running within the connective tissue matrix predominantly parallel to the
      circular sphincter muscle bundles. Profusely arborizing, highly varicose endings
      were also present in large myenteric ganglia of the antrum and duodenum, in the
      modified intramuscular ganglia, and in submucosal ganglia. Additionally, afferent
      fibers and terminals were present throughout the mucosal lining of the
      gastroduodenal junction. The branching patterns of some vagal afferents suggested
      that individual axons produced multiple collaterals in different compartments.
      NADPH-diaphorase positive, possibly nitroxergic neurons were present in myenteric
      ganglia of the immediately adjacent antrum and duodenum, and fine varicose fibers
      entered the sphincter muscle from both sides, delineating the potential vagal
      inhibitory postganglionic innervation. These morphological results support the
      view of a rich and differentiated extrinsic neural control of this important gut
      region as suggested by functional studies.

PMID- 7509722
TI  - Outer root sheath (ORS) cells organize into epidermoid cyst-like spheroids when
      cultured inside Matrigel: a light-microscopic and immunohistological comparison
      between human ORS cells and interfollicular keratinocytes.
AB  - In organotypic cultures, outer root sheath (ORS) cells of the human hair follicle
      develop into a stratified epithelium largely reminiscent of the epidermis; this
      apparently reflects their importance during wound healing. In the present study,
      ORS cells were grown inside a three-dimensional network of extracellular matrix
      proteins (Matrigel), together with different mesenchymal cells, in an attempt to
      mimic their follicular environment. Thus, inside Matrigel, ORS cells formed
      spheroids differentiating toward the center and showing all the markers of
      epidermal keratinization. Under identical conditions, normal epidermal
      keratinocytes developed similar spheroids, but of a significantly smaller size.
      Human dermal fibroblasts and dermal papilla cells, cocultured in the matrix, had
      a positive influence on both the proliferation and differentiation within both
      types of spheroids. Epidermal differentiation markers, such as suprabasal
      keratins, involucrin, filaggrin, gp80 and pemphigoid antigen, were readily
      expressed in ORS spheroids, whereas hard (hair) keratins were not detectable by
      immunostaining. Cells positive for an epithelial membrane antigen, strongly
      expressed in sebaceous glands, were seen in numerous spheroids. In contrast to
      organotypic "surface" epithelia, the expression and location of different
      integrin chains was normalized in ORS spheroids, indicating an enhanced
      mesenchymal influence in this in vitro system.

PMID- 7509723
TI  - Expression and functional analysis of murine B7 delineated by a novel monoclonal
      antibody.
AB  - The B cell surface molecule designated B7 has been shown to be expressed by
      activated human B cells and monocytes and to be a ligand for the CD28 and CTLA-4
      molecules on T cells. B7/CD28 interactions can provide a second signal to T cells
      (in addition to occupancy of the T cell antigen receptor) that is needed for T
      cell activation. COS cells transfected with the mouse homologue of B7 have been
      demonstrated to provide a stimulatory signal to murine and human T cells. In this
      report we describe a rat anti-mouse B7 mAb designated 1G10. Scatchard and/or FACS
      analyses utilizing 1G10 demonstrated that B7 was not expressed on resting splenic
      T cells or B cells, but could be induced at high levels on B cells cocultured
      with a syngeneic I-Ak-restricted autoreactive T cell hybridoma. Furthermore,
      activation of B cells with dibutyryl-cAMP (db-cAMP), a second messenger for class
      II MHC signaling, or with LPS induced the expression of B7 and the two agents
      showed additive effects. In contrast to B cells, freshly isolated mouse
      peritoneal macrophages constitutively expressed B7. Antibody-blocking experiments
      indicated that anti-B7 antibody partially inhibited T cell proliferative
      responses to primary antigenic stimulation but had no effect on the responses of
      previously activated T cells to antigenic restimulation.

PMID- 7509725
TI  - Role of calcium in the activation of mouse peritoneal macrophages: induction of
      NO synthase by calcium ionophores and thapsigargin.
AB  - Bacterial lipopolysaccharide (LPS) has been recognized as one of the most potent
      activating signals for mouse peritoneal macrophages. In macrophages primed by
      interferon-gamma (IFN-gamma) or trehalose dimycolate (TDM), LPS induces NO
      synthase and the events associated with a high nitric oxide output: antitumor and
      antiparasitic activities. In the present report, it is shown that drugs (calcium
      ionophores or thapsigargin) which elevate the concentration of cytosolic calcium,
      [Ca2+]i, induce NO synthase and antitumor activities in primed macrophages,
      mimicking LPS action. Calcium ionophores and thapsigargin trigger NO synthase
      activity in macrophages primed in vivo by TDM, in thioglycollate-elicited
      macrophages primed in vitro by IFN-gamma, and in IFN-gamma-treated EMT6
      adenocarcinoma cells. However, activation of TDM-primed macrophages by LPS does
      not seem to involve calcium fluxes: (i) no change in [Ca2+]i was detectable in
      TDM-primed macrophages loaded with Fura-2 and exposed to LPS, and (ii) activation
      of TDM-primed macrophages by LPS can be obtained in the presence of 4 mM EGTA. NO
      synthase expression is thus controlled in primed macrophages by two different
      pathways; calcium ionophores can replace LPS but do not act through the same
      intracellular cascade.

PMID- 7509724
TI  - Parallel costimulatory pathways promote myelin basic protein-stimulated
      proliferation of encephalitogenic rat T cells.
AB  - Activation pathways responsible for myelin basic protein (MBP)-stimulated
      proliferation of encephalitogenic T cells were studied by derivation of new
      monoclonal antibodies against rat T cell surface proteins. These monoclonal
      antibodies were derived by immunization of Balb/c mice with THYB-2 T cell hybrids
      or with the GP2.E5 line of encephalitogenic T-helper cells. The LRTC1 mAb
      inhibited MBP-stimulated IL-2 production by THYB-2 hybrids but not by THYB-1
      hybrids and did not inhibit the alternative response of MBP-induced growth
      inhibition by either hybrid subset. Although LRTC1 labeled virtually all rat
      leukocytes, it selectively inhibited proliferative responses to T cell mitogens
      but not to B cell mitogens. LRTC1 inhibited MBP-stimulated IL-2 production by
      GP2.E5 T cells but did not effectively block MBP-stimulated proliferation.
      Rather, LRTC1 acted in synergy with a second mAb (LRTC2) to effectively inhibit
      MBP-stimulated proliferation by GP2.E5 T cells. The observation that LRTC1 did
      not exhibit synergy with a third biologically active mAb (LRTC3) supported the
      hypothesis that LRTC1 and LRTC2 represented a specific combination of synergistic
      mAb. In contrast to the inhibitory activity on GP2.E5 T cells, LRTC1 and LRTC2
      synergistically stimulated antigen-independent IL-2 production by the THYB-1
      hybrid LSS-A1. These results support the hypothesis that GP2.E5 T cells respond
      to parallel costimulatory pathways that are respectively inhibited by LRTC1 and
      LRTC2 mAb. Furthermore, these synergistic mAb exhibited inhibitory or stimulatory
      activities that may be diagnostic of distinct T-helper cell subsets. These novel
      mAb may thereby facilitate studies of costimulatory pathways and T-helper cell
      subsets in the pathogenesis of autoimmune disease.

PMID- 7509726
TI  - The anti-CD6 mAb, IOR-T1, defined a new epitope on the human CD6 molecule that
      induces greater responsiveness in T cell receptor/CD3-mediated T cell
      proliferation.
AB  - The T lymphocyte cell surface molecule, CD6, has been shown in a number of
      studies to play an important role in T cell activation. Its physiological ligand
      or function is still unknown. A panel of five anti-CD6 mAbs was used in the
      present study to investigate the structure-function relationship of this
      molecule. Cross-blocking assays indicate that three different epitopes were
      defined on the CD6 molecule by these mAbs. One of these epitopes defined by the
      mAb, IOR-T1, is insensitive to thiol-reducing agents, such as dithiothreitol and
      2-mercaptoethanol. Of the other two epitopes, one was defined by 2H1 and the
      other was shared by three other mAbs, T12, 6D3, and Dako-CD6. All the CD6 mAbs at
      optimal concentration exhibit equal potency in enhancing T cell proliferation
      mediated through the T cell receptor/CD3 complex by optimal concentration of the
      anti-CD3 mAb, OKT3 (100 ng/ml). Simultaneous cross-linking of both the anti-CD6
      mAbs and OKT3 is essential for the synergistic effect. When suboptimal
      concentrations of OKT3 (1 ng/ml) were used (no detectable cell proliferation),
      the synergistic effect of the anti-CD6 mAbs was still evident but with a
      differential effect. The epitope defined by IOR-T1 consistently induced greater T
      cell responsiveness under these conditions. Our results suggest that the CD6
      molecule may play an important role in T cell activation, and that signals
      through an epitope of stable conformation appear to be of importance when antigen
      levels are low or interacting with low-avidity antigen receptors.

PMID- 7509727
TI  - Evidence for a structural difference in the CD7 polypeptide on human thymocytes
      and intraepithelial lymphocytes defined by a new monoclonal antibody, 3D9.
AB  - Intestinal intraepithelial lymphocytes (IEL) represent a distinct subpopulation
      of lymphocytes located on or above the basement membrane and adjacent to the
      basolateral membrane of enterocytes. Thus IEL are strategically positioned to
      mediate a response to the uptake of foreign antigens or to the alteration of
      enterocytes by injury or infection. Because of their unique location, we
      hypothesized that IEL might selectively express specialized cell surface proteins
      important in their site-specific localization or function. To identify such
      proteins, we immunized mice with purified human IEL and identified one monoclonal
      antibody, 3D9, which was found to react with a majority of IEL but with very few
      lamina propria lymphocytes (LPL) and weakly with most peripheral blood
      lymphocytes (PBL). Evaluation of this antibody with two-dimensional gels
      demonstrated that it reacts with CD7, previously known as an early thymocyte
      differentiation antigen. Interestingly, unlike all other anti-CD7 monoclonal
      antibodies, 3D9 identified only occasional thymocytes by immunohistochemistry
      suggesting that CD7 is structurally different on IEL and thymocytes. However, the
      CD7 polypeptide immunoprecipitated from IEL and thymocytes appeared identical in
      SDS-PAGE mobility and in charge by two-dimensional gels, despite being recognized
      differently by monoclonal antibodies. These studies emphasize the expression of
      CD7 by IEL T cells and reveal the existence of an undefined structural difference
      between CD7 molecules on IEL compared to thymocytes.

PMID- 7509728
TI  - Disruption of T lymphocyte reappearance in anti-Thy-1-treated animals in vivo
      with soluble CD44 and L-selectin molecules.
AB  - We used polyclonal rabbit anti-Thy-1 antiserum to eliminate T lymphocytes in the
      peripheral blood, lymph nodes, and spleens but not in the thymus of normal mice.
      T lymphocytes began to reappear in the peripheral lymphoid compartments 2 weeks
      after termination of the treatment. By 4 weeks, the numbers of peripheral T
      lymphocytes had recovered to normal levels. We found that injection of
      recombinant soluble forms of human CD44 or L-selectin but not human CD8 molecules
      delayed the reappearance of peripheral T lymphocytes in anti-Thy-1-treated mice.
      This delay in recovery most likely reflects the ability of these soluble
      receptors to interfere with lymphocyte migration in vivo. Our results provide in
      vivo evidence that CD44 and L-selectin regulates lymphocyte trafficking and
      suggest that soluble forms of both molecules provide useful tools for the study
      of lymphocyte migration in vivo.

PMID- 7509729
TI  - Suppression of experimental allergic encephalomyelitis in Lewis rats by
      administration of gangliosides.
AB  - Gangliosides (GA) are known to suppress T cell responses to mitogens and
      alloantigens. GA treatment (more than 50 mg/kg/rat subcutaneously every 12 hr)
      significantly suppressed clinical signs and histologic lesions of both actively
      induced and cell-transferred experimental allergic encephalomyelitis (EAE) in
      Lewis rats in a dose-dependent manner: P < 0.01, in actively induced EAE; P <
      0.001 (100 mg/kg) or P < 0.005 (50 mg/kg), in cell-transferred EAE. Lymph node
      cells from guinea pig myelin basic protein (GPMBP)-sensitized rats were
      stimulated in vitro with the specific sensitizing antigen, GPMBP, or with Con A.
      Purified bovine brain GA significantly suppressed GPMBP-induced proliferation in
      a dose-dependent manner (P < 0.01). GA treatment during sensitization phase (from
      Day -5 to Day 4) did not suppress actively induced EAE. There were no significant
      differences in T cell subsets of peripheral blood or spleen cells between GA
      treated rats and controls by flow cytometry analysis. Taken together, these
      findings indicate that GA primarily act on the immune effector phase of EAE.

PMID- 7509730
TI  - VCAM-1 influences lymphocyte proliferation and cytokine production during mixed
      lymphocyte responses.
AB  - The allogeneic mixed lymphocyte reaction (MLR) is regarded as an effective model
      for examining the events which occur during an allospecific immune response.
      Numerous studies have delineated the role of adherence molecule interactions
      during the MLR response. In the present study we have identified VCAM-1 as having
      a contribution to the generation of an allogeneic MLR response. These findings
      may have broad implications in vivo during antigen-specific and allograft
      rejection events. RT-PCR analysis was initially used to examine whether VCAM-1
      mRNA expression was observed during MLR responses and demonstrated peak
      expression between 12 and 48 hr of culture. Immunolocalization of VCAM-1 on
      adherent mononuclear phagocytes, but not nonadherent lymphocytes, from MLR
      cultures verified its expression during this response. Addition of anti-VCAM-1
      mAbs to MLR assays inhibited the proliferative response by over 70%, while
      addition of anti-VCAM-1 as late as Day 2 of the assay allowed significant
      inhibition of the proliferative response. This correlated with peak expression of
      VCAM-1 mRNA observed as late as 48 hr in RT-PCR analyses. In further studies,
      anti-VCAM-1 significantly inhibited peak expression of IL-2 on Days 3 and 4,
      while TNF-alpha production was diminished at 30 min and 1, 96, and 120 hr of
      culture, compared to control cultures. The production of macrophage inflammatory
      protein-1 alpha (MIP-1 alpha), a chemotactic cytokine which has an important role
      in vivo for the recruitment of leukocytes to a site of inflammation, was also
      significantly inhibited during peak production on Days 4 and 5 of the MLR assay.
      This study demonstrates novel findings of VCAM-1 expression during an allogeneic
      MLR response. The expression of VCAM-1 may have important implications during
      allospecific immune responses for the activation and proliferation of T
      lymphocytes as well as cytokine production.

PMID- 7509731
TI  - Sphingosine-mediated membrane association of DNA and its reversal by phosphatidic
      acid.
AB  - Resonance energy transfer was measured between egg phosphatidylcholine liposomes
      containing the intramolecular excimer forming pyrene-labelled phospholipid
      analogue 1,2-bis[pyren-1-(-yl)]decanoyl-sn-glycero-3-phosphocholine (bisPDPC) as
      a donor and DNA-bound adriamycin as an acceptor. Membrane association of DNA
      turned out to be critically dependent on the presence of sphingosine in the
      liposomes. Identical result was obtained by measuring the extent of quenching of
      the fluorescent DNA-bound dye Hoechst 33258 due to energy transfer to the
      lipophilic stain Nile Red incorporated in egg phosphatidylcholine liposomes
      containing varying amounts of sphingosine. The attachment of DNA to sphingosine
      containing membranes could be reversed by the further inclusion of the negatively
      charged phosphatidic acid up to approximately 1:2 PA/sphingosine molar ratio in
      the liposomes, thus suggesting the involvement of electrostatic interactions.
      Differential scanning calorimetry measurements confirmed a lack of association
      between DNA and dimyristoylphosphatidylcholine liposomes. Instead drastic changes
      were produced by DNA in the heat capacity scans measured for liposomes also
      incorporating sphingosine. Fluorescence microscopy revealed an extensive
      aggregation of sphingosine containing pyrene-phosphatidylcholine-labelled egg
      phosphatidylcholine liposomes in the presence of DNA. Together with other
      available data on the effects of sphingosine, the present findings suggest that
      sphingosine could directly alter the chromatin structure. Accordingly, such
      alterations may contribute to the control of replication and gene expression.

PMID- 7509732
TI  - The mechanism of the inhibition of squamous differentiation of rat tracheal 2C5
      cells by retinoic acid.
AB  - Retinoic acid (RA) plays an essential role in maintaining normal differentiation
      of tracheal epithelial cells. During vitamin A deficiency, tracheocytes undergo
      squamous metaplasia, an abnormal differentiation that can be reversed by RA. We
      used rat tracheal 2C5 cells to study the mechanism of inhibition of squamous
      differentiation by RA. 2C5 cells grown to confluence in the presence of serum
      underwent squamous differentiation as marked by an increase in their level of
      crosslinked envelope formation. The serum-induced crosslinked envelope formation
      was blocked by RA in 2C5 cells with an ED50 < 0.1 nM. However, the activity of
      the crosslinking enzyme, keratinocyte transglutaminase, did not correlate with
      the formation of crosslinked envelopes in 2C5 cells. Changes in biochemical
      markers of squamous differentiation such as an altered expression of specific
      cytokeratins also accompanied serum-induced squamous differentiation of 2C5
      cells. The expression of the keratin squamous differentiation markers (i.e. K13)
      were inhibited by RA, although the ED50 for K13 expression was > 1 nM. The
      different dose responses for RA inhibiting differentiation markers suggests
      multiple mechanisms of regulation by RA. These results indicate that 2C5 cells
      remain responsive to differentiation factors such as RA and serum despite being
      an immortalized cell line.

PMID- 7509734
TI  - Catecholamines stimulate the synthesis and release of insulin-like growth factor
      binding protein-1 (IGFBP-1) by fetal sheep liver in vivo.
AB  - In fetal sheep, prolonged hypoxia (for 24 h) induced by a reduction in maternal
      uterine artery blood flow, increases insulin-like growth factor binding protein-1
      (IGFBP-1) levels and decreases IGFBP-2 levels in the plasma, with corresponding
      changes in messenger RNA (mRNA) levels in the liver. Since IGFBP-1 synthesis in
      liver cells in vitro is stimulated by compounds that increase intracellular cAMP
      concentrations, we hypothesized that the increased IGFBP-1 synthesis during
      prolonged hypoxemia may be induced by circulating catecholamines, that are
      released during hypoxia, and that elevate fetal liver cAMP levels. Our aim was to
      determine the effect of 24-h catecholamine infusions on the synthesis and release
      of IGFBP-1 and IGFBP-2 in fetal sheep. Vascular catheters were implanted into
      fetuses at 110-115 days gestation in 14 pregnant ewes. After a 5-day recovery
      period, fetuses received a 24-h infusion of either norepinephrine (1
      micrograms/kg.min, n = 5), epinephrine (0.25 micrograms/kg.min, n = 5), or
      vehicle (normal saline, n = 4). Fetal carotid arterial samples were collected at
      specified intervals throughout the infusion for the determination of blood
      glucose concentrations, plasma catecholamine concentrations by HPLC, insulin, and
      glucagon concentrations by RIA, and IGFBP levels by Western ligand blotting.
      After 24 h, the ewe and fetus were killed and selected fetal tissues (liver and
      kidney) were collected, and analyzed for IGFBP mRNA levels by northern blotting
      followed by laser densitometric quantification. Plasma catecholamine
      concentrations were increased in treated fetuses to levels that may be expected
      in fetuses subjected to prolonged hypoxia. In epinephrine and norepinephrine
      infused fetuses, blood glucose and plasma glucagon concentrations were increased
      significantly, whereas plasma insulin concentrations were decreased
      significantly. Norepinephrine and epinephrine infusions increased IGFBP-1 levels
      significantly (2- to 5-fold) in fetal plasma within 8-12 h, and the time course
      pattern of elevation of plasma IGFBP-1 levels was similar to that observed in
      prolonged hypoxia. After 24 h of either norepinephrine or epinephrine infusion,
      IGFBP-1 mRNA levels in the liver of fetuses were increased significantly (5- to 7
      fold) compared to those of vehicle infused fetuses. IGFBP-2, -3, and -4 levels in
      fetal plasma were not affected by either infusion, nor were IGFBP-2 mRNA levels
      in fetal liver and kidney.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7509736
TI  - Hormonal regulation and biological actions of insulin-like growth factor binding
      proteins in isolated ovine thyroid follicles.
AB  - The ability of TSH to stimulate synthesis and release of thyroid hormones in
      ovine thyroid follicles in vitro depends partially on a synergy with insulin-like
      growth factors (IGFs). The cellular availability of IGFs may be influenced by the
      release of several IGF binding proteins (IGFBPs). The purposes of these studies
      was to 1) further characterize the species of IGFBPs synthesized by thyroid
      follicles, 2) examine the ability of TSH and cortisol to alter IGFBP gene
      expression and protein release, and 3) investigate the actions of exogenous
      IGFBPs on thyroid cell function. Adult sheep thyroid follicles were isolated
      after collagenase digestion, grown to confluence in Coon's modified Ham's F12M
      medium (OH) with the addition of transferrin, glycylhistidyl-lysine, somatostatin
      (3H), cortisol and insulin, and maintained in serum-free test media with or
      without further supplements for up to 48 h. Conditioned media were analyzed for
      IGFBP presence by Western ligand blotting, and by immunoblotting using specific
      antisera against bovine IGFBP-2 and human IGFBP-5. IGFBP mRNAs from follicles
      were identified by Northern blot hybridization using [32P]labeled complementary
      DNAs encoding ovine IGFBP-1 or -2, and rat IGFBP-4, -5, or -6. Uptake and
      organification of Na[125I] were measured by incorporation into trichloroacetic
      acid-precipitable material. Isolated thyroid follicles synthesized four species
      of IGFBPs in either 0H or 3H medium as detected by ligand blotting, of sizes 40
      46, 34, 28, and 18 kilodaltons (kDa), respectively. The 32 kDa IGFBP was
      identified immunologically as IGFBP-2, whereas the 28 kDa and 18 kDa species were
      identified as IGFBP-5. Northern blot hybridization of total RNA from cells in 3H
      medium demonstrated an IGFBP-2 messenger RNA (mRNA) [1.4 kilobase (kb)], an IGFBP
      4 mRNA (2.6 kb), and two IGFBP-5 mRNAs (6 kb and 1.8 kb). No IGFBP-1 or -6 mRNAs
      were detected. Incubation of cultured follicles with TSH (30-500 microU/ml)
      caused a dose-dependent decrease in the abundance of all IGFBP mRNAs and released
      proteins, which were reduced further by TSH together with cortisol (10 nM). When
      the inhibitory effect of TSH and cortisol was removed, IGFBP-2 mRNA increased
      within 3 h and was 7-fold greater within 12 h. IGFBP-2 did not appear in the
      conditioned medium until 12 h after TSH removal, along with the other IGFBP
      species.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7509735
TI  - Development, characterization, and application of monoclonal antibodies to the
      native and synthetic beta COOH-terminal portion of human chorionic gonadotropin
      (hCG) that distinguish between the native and desialylated forms of hCG.
AB  - Although the pregnancy hormone hCG has been extensively mapped immunochemically,
      few monoclonal antibodies have been produced to the unique COOH-terminal region
      of its beta-subunit (beta CTP). We now report the development and
      characterization of five such monoclonal antibodies. Three of these antibodies
      were developed to the synthetic peptide analog of the hCG beta-(109-145) region
      coupled to diphtheria toxoid, and two antibodies to a conjugate of bovine
      thyroglobulin and the peptide hCG beta-(115-145) prepared from hCG with its
      carbohydrate moieties intact. The monoclonal antibodies raised against the
      synthetic peptide bound hCG, desialylated hCG, and synthetic peptide to a similar
      extent, whereas antibodies generated to the natural hCG peptide did not bind to
      the synthetic peptide analog of the COOH-terminal peptide (beta CTP) region or to
      desialyated hCG. These new monoclonal antibodies could distinguish between native
      and desialyated hCG in liquid phase immunoassays as well as by Western blots.
      They are highly specific reagents for such Western blotting and were used for
      studies of a crude human pituitary gonadotropin preparation to demonstrate that
      it contained intact hCG beta without the internal peptide bond cleavages found in
      the subunit present in human blood and urine. Competition experiments using
      combinations of monoclonal antibodies and rabbit anti-beta CTP antiserum
      demonstrated that two epitopes exist within the beta-(115-145) region of hCG, one
      of which depends on the presence of carbohydrate. In summary, the new monoclonal
      hCG beta CTP antibodies reported here can 1) discriminate between native and
      desialylated hCG, 2) identify hCG and nicked hCG on Western blots, 3) provide an
      immunoaffinity purification tool for hCG, and 4) bind to two distinct epitopes on
      the beta CTP.

PMID- 7509733
TI  - Up-regulation of nitric oxide synthase (NOS) gene expression together with NOS
      activity in the rat hypothalamo-hypophysial system after chronic salt loading:
      evidence of a neuromodulatory role of nitric oxide in arginine vasopressin and
      oxytocin secretion.
AB  - Chronic salt loading up-regulated the expression of neuronal nitric oxide
      synthase (NOS) mRNA in the supraoptic nucleus (SON) and paraventricular nucleus
      (PVN) of the hypothalamus with a concomitant increase in NOS activity in the
      posterior pituitary. Once daily ip injection of N-omega-nitroarginine (N-Arg), a
      NOS inhibitor, significantly inhibited NOS activity in the posterior pituitary in
      a dose-dependent manner, but did not influence NOS mRNA levels. Two percent salt
      loading for 3 or 4 days significantly depleted the contents of both arginine
      vasopressin (AVP) and oxytocin (OT) in the posterior pituitary, and simultaneous
      treatment with daily injections of N-Arg at a dose of 10 mg/kg significantly
      enhanced the depletion of both AVP and OT. This effect was dose dependent and
      paralleled the inhibition of NOS activity in the posterior pituitary. N-Arg
      treatment had no effect on the levels of both AVP and OT transcripts in PVN or
      SON. These results suggest that NOS gene expression in the SON and PVN of the rat
      hypothalamus is increased during hyperosmotic stimulation and suggest a
      neuromodulatory role for NO in the rat hypothalamo-hypophysial system as an
      inhibitory regulator of AVP and OT secretion.

PMID- 7509737
TI  - Insulin-like growth factor binding protein-3 is functionally altered in pregnancy
      plasma.
AB  - In a variety of physio-pathological conditions, but also in the normal state,
      calcium-dependent serine protease(s) partially proteolyze proportions of
      circulating insulin-like growth factor binding protein-3 (IGFBP-3). This occurs
      without disrupting the 150-kilodalton (kDa) complexes in which IGFBP-3 carries of
      most of the IGF-I and IGF-II in serum. In this work we show that the 150-kDa
      complex is functionally altered during pregnancy, which is when the largest
      proportion of IGFBP-3 is proteolyzed. After preincubation at 4 C with [125I]IGF-I
      or -II with or without 1 microgram unlabeled IGF-I or -II, pooled plasma samples
      were gel filtered at pH 7.4. Larger proportions of labeled IGFs were found in the
      150-kDa complexes of the third trimester pregnancy plasma pool than in those of
      the normal plasma pool, suggesting increased binding capacity. Nevertheless,
      competitive binding experiments using [125I]IGF-I and -II and IGFBP-3
      preparations from each of the plasma pools showed that the competitive potencies
      of IGF-II and especially IGF-I were lower in pregnancy IGFBP-3 than in normal
      IGFBP-3. Scatchard analysis revealed a 2-fold loss of affinity for IGF-II and a
      10-fold loss for IGF-I compared with that for normal plasma IGFBP-3. In studies
      at 37 C of the kinetics of dissociation of [125I]IGF-I and -II bound to IGFBP-3,
      IGF-II was dissociated 6 times faster, and IGF-I 10 times faster from pregnancy
      plasma IGFBP-3 than from normal plasma IGFBP-3. After incubation of individual
      plasma samples at 37 C and gel filtration at room temperature (in the presence of
      EDTA), IGFs were assayed in the three circulating pools (150-kDa and 40-kDa
      complexes and free IGFs), revealing a redistribution of pregnancy plasma IGFs.
      The proportion of total IGF-I in free form was nearly three times greater in
      pregnancy than in normal plasma (11.4% vs. 4.1%, P < 0.005), whereas that of free
      IGF-II was slightly smaller (1.5% vs. 2%). In the 150-kDa complexes, the
      proportion of total IGF-I was significantly smaller in pregnancy than in normal
      plasma, and that of IGF-II was greater. In the 40-kDa complexes, the proportion
      of total IGF-II was significantly smaller. The mean ratios of molar
      concentrations of free IGF-I/IGF-II were 0.43 in normal plasma and 2.23 in
      pregnancy plasma (P < 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7509742
TI  - Endoscopic treatment of upper gastrointestinal tract malignancies.
AB  - Palliative endoscopic treatment of the upper gastro-intestinal (UGI) tract
      includes: dilation, Nd:YAG laser photocoagulation and intubation, used alone or
      in combination. These procedures are usually performed on an outpatient basis and
      are associated with a low rate of morbidity and mortality. From 1978 to 1992, 836
      patients were treated at the Endoscopy Division of the Istituto Nazionale Tumori,
      Milan, for inoperable primary or recurrent malignancies of the UGI-tract.
      Recanalization was obtained in 96% of patients treated; functional results have
      been computed according to the site and to the endoscopic method. Overall median
      survival was 6.2 months. The complication rate was 8%. Relief of dysphagia is the
      goal of palliative treatment in patients with inoperable neoplasms of the UGI
      tract.

PMID- 7509739
TI  - Extrapituitary actions of gonadotropin-releasing hormone: stimulation of insulin
      like growth factor-binding protein-4 and atresia.
AB  - To understand how the intrinsic GnRH system functions in the ovary, we tested the
      effects of GnRH agonist (GnRH-a) on insulin-like growth factor-binding protein-4
      (IGFBP-4) production, a novel marker of atresia. We also tested the ability of
      GnRH-a to stimulate atresia in vivo. When rat granulosa cells were cultured in
      defined medium for 2 days (controls), relatively large amounts of the 24,000
      relative molecular mass IGFBP-4 accumulated in the medium. FSH (100 ng/ml)
      inhibited control IGFBP-4 protein levels and stimulated IGFBP-4 protease
      activity. GnRH-a increased (up to 4-fold) IGFBP-4 accumulation in the medium
      (ED50 = 1 x 10(-10) M), and the effect was blocked by a GnRH antagonist. Neither
      GnRH-a nor its antagonist had a detectable effect on protease activity. In
      coincubation experiments, GnRH-a effectively inhibited (ED50 = 3 x 10(-11) M) the
      FSH responses, and the effect of GnRH-a was blocked by GnRH antagonist. A 6-day
      time-course experiment showed that IGFBP-4 accumulation in control cultures
      remained constant for 2 and 4 days, after which it was undetectable. FSH (100
      ng/ml) produced no measurable IGFBP-4 over the 6-day time course. The levels of
      IGFBP-4 increased markedly during the first 2 days of GnRH-a treatment, but were
      not significantly different from control levels on days 4 and 6. Similar results
      were obtained when cells were treated with FSH plus GnRH-a. Treating immature
      hypophysectomized estrogen-primed rats with GnRH-a in vivo caused a rapid and
      dramatic decrease (average, 60%) in the mitotic index of the granulosa cells of
      all preantral follicles (healthy and atretic) and increased pyknosis. These
      results demonstrate that 1) GnRH-a stimulates the expression of IGFBP-4 protein
      in rat granulosa cells in vitro; 2) GnRH-a abolishes the ability of FSH to
      inhibit IGFBP-4 expression and induce IGFBP-4 protease activity; and 3) GnRH-a
      stimulates atresia in preantral follicles in vivo. These results support the
      hypothesis that autocrine/paracrine secretion of ovarian GnRH might cause atresia
      by mechanisms involving increased IGFBP-4 synthesis.

PMID- 7509740
TI  - Hormonal control of growth in the genetically obese Zucker rat. I. Linear growth,
      plasma insulin-like growth factor-I (IGF-I) and IGF-binding proteins.
AB  - The genetically obese Zucker rat is a widely used model of early-onset obesity.
      Like obese children, these obese rats are hyperinsulinemic and have low GH
      secretion. However, data on linear growth and insulin-like growth factor-I (IGF
      I) levels in this model are scanty and contradictory. In the present study, we
      investigated linear growth and its hormonal control in Zucker rats (male and
      female) from 4-20 weeks of age. In the obese animals, compared to their lean
      littermates, the naso-anal length was normal or slightly greater, whereas the
      tails and femurs were shorter. The plasma concentration of IGF-I increased
      between 4-20 weeks of age, and IGF-I levels were normal or slightly higher in the
      obese animals. The serum level of IGF-binding protein-3 (IGFBP-3) measured by
      Western ligand blotting was not significantly different in lean vs. obese rats.
      To assess the IGF-I response to GH, bovine GH was administered (250
      micrograms/100 g BW, ip, daily for 3 days) to 16- to 20-week-old female Zucker
      rats; plasma IGF-I concentrations increased more in the obese (percent increase
      over baseline, 347 +/- 44% vs. 194 +/- 31%; P < 0.01). These results show that
      despite low GH secretion, genetically obese Zucker rats have 1) normal linear
      (nasoanal) growth, 2) normal or increased circulating levels of IGF-I and IGFBP
      3, and 3) increased plasma IGF-I responses to exogenous GH. These results suggest
      that the GH-independent growth in this model could result from direct effects of
      hyperinsulinism on circulating IGF-I and IGFBP-3 levels and/or indirect effects
      through increased GH receptor function.

PMID- 7509741
TI  - Differential regulation of insulin-like growth factor I (IGF-I) and IGF binding
      protein-1 messenger ribonucleic acids by amino acid availability and growth
      hormone in rat hepatocyte primary culture.
AB  - To determine the mechanisms involved in the nutritional regulation of insulin
      like growth factor I (IGF-I) production and action, we studied the regulation of
      IGF-I and IGF-Binding Protein 1 (IGFBP-1) gene expression by GH and amino acid
      availability in rat hepatocyte primary culture. Hepatocytes were isolated by in
      situ collagenase perfusion and cultured on Matrigel in serum-free medium
      containing insulin and hydrocortisone. Rat GH (500 ng/ml) increased IGF-I
      messenger RNA (mRNA) abundance 6.9-fold at 24 h, as measured by Northern Blot
      using an IGF-I-specific riboprobe. In contrast, IGFBP-1 mRNA levels were
      decreased by 41% after 24 h of rat GH treatment. Hepatocytes were incubated for
      24 h in three media differing in their amino acid concentrations: 0.2X, 1X, and
      5X the normal rat plasma concentration. Amino acid deprivation (0.2X) decreased
      the abundance of IGF-I mRNAs (-56% after 24 h), whereas amino acid excess (5X)
      increased it (+70%) in comparison to the 1X medium. In contrast, amino acid
      deprivation increased IGFBP-1 mRNA abundance (+69%), whereas excess decreased it
      (-75%). Studies of the interaction between GH and amino acids, accomplished by
      the simultaneous manipulation of the two, suggest that each factor modulates the
      IGF-I mRNA and the IGFBP-1 mRNA and protein response to the other. We conclude
      that the IGF-I and IGFBP-1 genes are regulated in opposite ways by GH and amino
      acid availability. Our observations suggest that amino acids and GH regulate the
      production of IGF-I directly and exert indirect effects on IGF-I action by
      regulating the production of IGFBP-1.

PMID- 7509738
TI  - Evidence for an in vivo role of insulin-like growth factor-binding protein-1 and 
      2 as inhibitors of collagen gene expression in vitamin C-deficient and fasted
      guinea pigs.
AB  - Acutely scorbutic and fasted (vitamin C-supplemented) guinea pigs exhibit
      decreased collagen gene expression associated with weight loss. We recently
      demonstrated that circulating insulin-like growth factor-binding protein-1 and -2
      (IGFBP-1 and -2) are induced in these deficiencies, and that removal of IGFBP-1
      and -2 from serum of such animals by specific antibodies reverses inhibition of
      cellular IGF-I-dependent functions, including collagen and DNA synthesis. Here we
      investigated the kinetics of induction of IGFBP-1 and -2 relative to suppression
      of collagen gene expression. Guinea pigs were fasted for 10-96 h, with 3-24%
      weight loss, or received an ascorbate-free diet for up to 4 weeks, with 5-28%
      weight loss during the third and fourth weeks (phase II of scurvy). In both
      deficiencies, there was noncoordinate regulation of collagen mRNA expression in
      tissues. Type I collagen mRNA concentrations in skin decreased rapidly after 5
      10% weight loss and reached about 10% of normal levels, whereas in bone, there
      was a later, and not as extensive, decrease. The concentration of cartilage type
      II collagen mRNA decreased rapidly initially, but then remained at 40-50% of
      normal. Circulating IGF-I concentrations remained normal during the period when
      collagen gene expression was initially suppressed, although there was a later
      decrease. In contrast, mRNAs for IGFBP-1 and -2 and the circulating proteins were
      induced before or concomitantly with the suppression of collagen gene expression.
      The ability of fasted or scorbutic guinea pig sera to inhibit IGF-I action in
      cells increased in parallel with IGFBP activity ([125I]IGF-I binding), which, in
      turn, mainly reflected the concentration of IGFBP-1 in sera. Serum insulin may be
      the primary regulator of the IGFBPs. Its levels were decreased to 10-13% of
      normal when weight loss commenced, whereas cortisol levels, although increased,
      did not correlate with the induction of IGFBPs. The overall results taken
      together with our recent findings from cell culture experiments are compatible
      with circulating IGFBP-1 and -2 acting as inhibitors of collagen gene expression
      by blocking IGF-I action during fasting and phase II of vitamin C deficiency.

PMID- 7509743
TI  - Cancer of the oesophagus--palliation--laser treatment and combined procedures.
AB  - Today, laser photodestruction is a low-risk, easily applied standard procedure
      for the palliation of malignant stenoses of the oesophagus, the aim of which is
      to recanalize the stenosis and improve the patient's quality of life. This is
      confirmed by our own experience in 130 patients, in 96% of whom recanalization
      proved successful and reproducible at any time. Complications requiring treatment
      were seen in less than 10% of the cases, and all responded to conservative
      therapy; only one patient died. In patients with squamous cell carcinoma, the use
      of complementary measures possibly results in a limited prolongation of survival.
      Photodynamic therapy offers further possibilities, although its clinical use in
      gastroenterology is presently restricted to early superficial tumours.

PMID- 7509744
TI  - Photodynamic therapy in gastroenterology--current status and future prospects.
AB  - Photodynamic therapy (PDT) is a promising technique for producing localized
      destruction of small cancers in the gastrointestinal tract. Following prior
      intravenous administration of a photosensitizing drug, the tumour area is exposed
      to low power red light from a laser. There is a small degree of selectivity for
      tumour areas, but even if there is damage to normal tissues, this heals by
      regeneration. Thus the tumour and a surrounding cuff of normal tissue can be
      treated without the need for surgery and with safe healing of all treated areas
      without risk of perforation. There are 2 main problems. PDT can only be applied
      to small tumours (up to 1-2 cm thick) partly because the red light used only
      penetrates a few mm into tissue, but also because there is a risk of delayed
      haemorrhage following partial necrosis of large lesions. However, it may be
      complementary to other techniques. If the main bulk of a cancer is removed by
      surgery, PDT may be able to destroy any small areas of remaining cancer that are
      not accessible for resection. The other problem is that the most frequently used
      photosensitizer, haematoporphyrin derivative (HpD), leaves the patient sensitive
      to sunlight for several weeks after treatment. This will be much less of a
      problem with the newer photosensitizers such as aluminium sulphonated
      phthalocyanines and amino laevulinic acid, both of which should be ready for
      preliminary clinical trials within a few months. PDT has been applied on its own
      for the palliation of dysphagia from advanced oesophageal cancers, but the
      results as far are purely anecdotal and it seems unlikely that this will prove a
      useful approach unless PDT is combined with other therapies. The potential for
      PDT in treating gastrointestinal tumours is great, but a careful understanding of
      the biology involved is essential before this can be realized.

PMID- 7509746
TI  - Complex formation between protein C inhibitor and prostate-specific antigen in
      vitro and in human semen.
AB  - Protein C inhibitor (PCI), a serine-proteinase inhibitor first purified from
      human blood plasma, occurs at high concentrations (3-4 microM) in seminal fluid
      in both a high-molecular-mass and low-molecular-mass form. Immunochemical data
      have previously suggested that PCI in seminal plasma forms complexes with the
      most abundant serine proteinase in semen, prostate-specific antigen (PSA). To
      provide a structural characterization of the PCI target, immunodetected as PSA, a
      procedure was developed to isolate low-molecular-mass and high-molecular-mass
      forms of PCI from seminal fluid. The high-molecular-mass form of PCI, recognized
      by monoclonal antibodies against PSA, was dissociated by alkaline treatment into
      the low-molecular-mass form of PCI and a 33-kDa protein identified as PSA by 25
      conclusive steps of N-terminal sequence analysis. We developed a sensitive
      immunofluorometric assay (IFMA) to measure PCI-PSA complexes in body fluids and
      investigated the rate at which purified PSA may form complexes with purified PCI.
      Formation of complexes detected by this IFMA and the appearance of SDS-stable
      approximately 90-kDa complexes paralleled loss of PSA activity recorded with
      chromogenic substrates. The rate of complex formation was slow compared to that
      reported for PCI and activated protein C, but was enhanced up to sixfold in the
      presence of heparin. Less than 10% of the initial PSA activity remained after 3 h
      incubation with a sevenfold molar excess of PCI and in the presence of heparin.
      In freshly collected ejaculates, the rate of PCI-PSA complex formation measured
      by IFMA was similar to that observed between the purified proteins, and
      paralleled the appearance of SDS-stable complexes by immunoblotting. During gel
      dissolution in freshly collected ejaculates, approximately 40% of immunodetected
      PCI becomes complexed to PSA. Although PCI is a slow inhibitor of PSA, complexes
      between PCI and PSA are detected at levels that correspond to an inactivation of
      up to 5% of the PSA activity in the ejaculate.

PMID- 7509745
TI  - Light-activated cleavage of DNA by cobalt-bleomycin.
AB  - We have studied the light-activated cleavage of DNA by cobalt-bleomycin using a
      series of synthetic DNA fragments containing (AT)n and (GC)n. This cleavage
      reaction requires high concentrations of the antibiotic and appears to be a
      stoichiometric process rather than a catalytic process. We find that, in common
      with the iron-complex, cobalt-bleomycin can cleave at ApT steps within regions of
      alternating AT residues; ApT steps within other sequences including (AAT)n.
      (ATP)n are not good substrates for cobalt-bleomycin cleavage. Some repetitive
      regions display an alternating pattern of cleavage products, revealing the
      preferred arrangement of ligand molecules along a saturated DNA lattice. A
      similar repetitive pattern is found for diethylpyrocarbonate modification and
      hydroxyl-radical cleavage. Although cleavage of ApT and GpC proceeds at
      equivalent rates, the data suggest that bleomycin binds more tightly to the
      latter. Adenine residues on the 3' side of both GpC-cleavage and ApT-cleavage
      sites are rendered more reactive to diethylpyrocarbonate, consistent with a
      ligand-induced alteration in local DNA structure. The cobalt-bleomycin-binding
      site consists of not more than four base pairs, and may be as small as three base
      pairs.

PMID- 7509747
TI  - N-Acetylserotonin prevents the hypotension induced by bacterial
      lipopolysaccharides in the rat.
AB  - Nitric oxide is produced by the NO synthase, which catalyses the conversion of
      arginine to citrulline and NO using tetrahydrobiopterin as an essential cofactor.
      N-Acetylserotonin, an inhibitor of the tetrahydrobiopterin biosynthesis, given 30
      min before bacterial lipopolysaccharide to anesthetized rats, inhibited both the
      decrease in blood pressure and the increase in nitrite plasma levels induced by
      lipopolysaccharide. Thus, during endotoxemia the availability of
      tetrahydrobiopterin appears to be essential for the activity of NO synthase.

PMID- 7509748
TI  - Differences in the effects of tachykinin NK1 receptor antagonists: neuronal
      versus smooth muscle tissues.
AB  - The effects of three tachykinin NK1 receptor antagonists (L-668,169, (+/-)-RP
      67580, and (+/-)-CP 96.345) were examined for their ability to antagonise
      responses evoked by substance P O-methyl ester (a selective NK1 receptor agonist)
      in isolated neuronal tissue (rat superior cervical ganglia and guinea-pig locus
      coeruleus) and smooth muscle tissues (rat urinary bladder and guinea-pig ileum
      longitudinal muscle/myenteric plexus). (+/-)-RP 67580 was similarly effective in
      antagonising responses in both rat superior cervical ganglia and urinary bladder
      (estimated pKa value = 7.4 for both tissues); however, (+/-)-CP 96,345 was 50
      fold less effective in antagonising responses in guinea-pig locus coeruleus than
      in ileum longitudinal muscle/myenteric plexus (estimated pKa values = 7.6 and 9.3
      respectively). It is suggested that the differential effects of (+/-)-CP 96,345
      may reflect the existence of a population of NK1 receptors within guinea-pig
      locus coeruleus that are less sensitive to the effects of this NK1 receptor
      antagonist.

PMID- 7509749
TI  - Metabotropic and ionotropic excitatory amino acid receptor agonists induce
      different behavioral effects in mice.
AB  - Intracerebroventricular (i.c.v.) infusion in mice of the selective metabotropic
      excitatory amino acid receptor agonist 1S,3R-1- aminocyclopentane-1,3
      dicarboxylate (1S,3R-ACPD) (0.6-575 nmol/min) dose dependently induced face
      washing and scratching. In contrast, the subtype-specific ionotropic excitatory
      amino acid receptor agonists N-methyl-D-aspartate (NMDA), kainate and alpha-amino
      3-hydroxy-5-methylisoxazole-4-propionate (AMPA) (0.3-3.0 nmol/min) dose
      dependently induced clonic convulsions. I.c.v. infusion of the non-selective
      metabotropic receptor agonists ibotenate (6 nmol/min) or quisqualate (30
      nmol/min) induced clonic convulsions. However, when ionotropic receptors were
      blocked with (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)cyclohepten-5,10-imine
      maleate (MK-801, dizoclipine) (3 nmol/min) or 2,3-dihydroxy-6-nitro-7- sulfamoyl
      benzo(f)-quinoxaline (NBQX) (9 nmol/min), respectively, face washing and
      scratching behavior emerged. Neither MK-801 or NBQX (ED50 value > 100 nmol/min),
      nor the putative metabotropic receptor antagonist L-amino-3-phosphoro-propionic
      acid (L-AP3) (> 176 nmol/min); nor the dopamine receptor antagonists SCH 23390 (>
      74 nmol/min), metoclopramide (> 89 nmol/min) and haloperidol (> 27 nmol/min)
      antagonized 1S,3R-ACPD-induced scratching (144 nmol/min). These results suggest
      that the behavioral consequences of i.c.v. infusion of 1S,3R-ACPD in mice reflect
      a selective activation of metabotropic receptors that differs from the behavioral
      changes observed with i.c.v. infusion of ionotropic receptor agonists.

PMID- 7509750
TI  - Interleukin-1 contributes to the induction of nitric oxide synthase by endotoxin
      in vivo.
AB  - We investigated the role of interleukin-1 in the induction of a Ca(2+)
      independent nitric oxide (NO) synthase by bacterial endotoxin in vivo. In
      anaesthetized rats, pretreatment with interleukin-1 receptor antagonist
      (interleukin-1ra; 16 mg kg-1 i.v., followed by an infusion of 2.4 mg kg-1 h-1)
      ameliorated the delayed hypotension and tachycardia in response to endotoxin (2
      mg kg-1 i.v.). Endotoxaemia for 3 h induced a Ca(2+)-independent NO synthase
      activity in the lung and reduced the contractions to noradrenaline in the
      thoracic aorta ex vivo. Treatment with interleukin-1ra attenuated both the
      induction of NO synthase in the lung (by 46 +/- 5%) and the endotoxin-induced
      hyporeactivity to noradrenaline in the aorta. Thus, endogenous interleukin-1
      contributes to the induction of NO synthase in response to endotoxin in vivo.

PMID- 7509751
TI  - Blockade of tachykinin NK1 receptors by CP-96345 enhances dopamine release and
      the striatal dopamine effects of methamphetamine in rats.
AB  - The nonpeptide, tachykinin NK1 receptor antagonist, CP-96345, permits the study
      of the physiological role of extrapyramidal substance P systems. Using
      microdialysis, we observed that locally applied CP-96345 (200 nM) caused a
      significant increase in dopamine release in the striatum as well as substantially
      enhancing striatal dopamine release caused by a low dose of methamphetamine (0.5
      mg/kg s.c.). In addition, multiple systemic administrations of CP-96345 almost
      doubled the dopamine-mediated responses of the striatal neurotensin and dynorphin
      systems to high doses of methamphetamine (10 mg/kg/dose s.c.). Our findings
      suggest that the physiological role of substance P released in the striatum is to
      decrease the activity of the nigrostriatal dopamine pathway.

PMID- 7509752
TI  - Substance P-induced contractions of the guinea-pig proximal colon through
      stimulation of post-junctional tachykinin NK1 receptors.
AB  - The effects of three tachykinin NK1 receptor antagonists and a tachykinin NK2
      receptor antagonist against substance P-induced contractions of the guinea-pig
      proximal colon longitudinal muscle were investigated. Atropine, tetrodotoxin and
      phosphoramidon did not affect the concentration-response curve for substance P
      (pEC50 = 7.8). The tachykinin NK1 receptor antagonist, 2S,3S-cis-CP 96345,
      competitively inhibited the contractions due to substance P (pA2 = 8.5;
      constrained pA2 = 8.9), but at higher concentrations (> or = 3 x 10(-7) M), 2S,3S
      cis-CP 96345 also depressed the concentration-response curve for methacholine.
      The species-selective tachykinin NK1 receptor antagonists, WIN 51708 and WIN
      62577 (both 1 x 10(-6) M), and the tachykinin NK2 receptor antagonist, SR 48968
      (3 x 10(-7) M), had no effect. It is concluded that substance P induces
      contractions through the stimulation of tachykinin NK1 receptors on the smooth
      muscle cells. In this preparation, tachykinin NK2 receptors do not seem to be
      involved in the contractile action of substance P.

PMID- 7509753
TI  - Metabotropic excitatory amino acid receptor agonists selectively potentiate
      behavioral effects induced by ionotropic excitatory amino acid receptor agonists
      in mice.
AB  - The behavioral consequences of co-activation of metabotropic and ionotropic
      excitatory amino acid receptors were studied in mice using
      intracerebroventricular (i.c.v.) co-infusion of the metabotropic receptor agonist
      1S,3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD) with the subtype
      specific ionotropic receptor agonists N-methyl-D-aspartate (NMDA), kainate and
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). I.c.v. co-infusion
      of ionotropic receptor agonists (0.3-3 nmol/min) with a fixed dose of 1S,3R-ACPD
      (144 nmol/min) decreased time to onset of clonic convulsions (P < 0.05).
      Pretreatment with i.c.v. infusion of 72 nmol of 1S,3R-ACPD reduced time to onset
      of convulsions induced by an intravenous (i.v.) infusion of NMDA (P < 0.05) but
      had no effect on convulsions induced by pentylenetetrazol. These results reveal
      that activation of the metabotropic excitatory amino acid receptor selectively
      potentiates the behavioral response following activation of the ionotropic
      excitatory amino acid receptors.

PMID- 7509754
TI  - Seroprevalence of hepatitis B and C in a Merseyside hospital for the mentally
      handicapped.
AB  - This study reports the prevalence of antibodies to hepatitis B virus (HBV) and C
      virus (HCV), and the frequency of potential exposure to these viruses among
      patients and staff in six long-stay wards of a hospital caring for mentally
      handicapped adults from the Mersey region. A retrospective survey of risk
      behaviour among 134 patients and questionnaire survey of 75 nursing staff was
      performed. Serum samples from both groups were tested for HBV markers and patient
      sera for antibodies to HCV by enzyme-linked immunosorbent assay (ELISA). None of
      the 102 patients tested had antibodies against HCV, although 17 had detectable
      antibody to HBV core (anti-HBc). Seven out of the 17 were positive for HBV
      surface antigen. None was positive for IgM antibody to HBV core. Only 1 out of 61
      staff had anti-HBc and none was positive for surface antigen. Twenty-nine of 75
      (39%) staff reported bites sufficient to break the skin and 52 (69%) significant
      other injuries from patients; 25 (31%) of staff had not received HBV vaccination.
      None of the patients had received HBV vaccine. We conclude that HCV does not
      appear to be a major hazard in this closed community but the prevalence of HBV
      markers indicating past exposure among patients is high, vaccine uptake is
      incomplete and incidents which may allow viral transmission are frequent.

PMID- 7509756
TI  - Plasmodium falciparum: pfalhesin and CD36 form an adhesin/receptor pair that is
      responsible for the pH-dependent portion of cytoadherence/sequestration.
AB  - The cytoadherent behavior of two Plasmodium falciparum (human malaria) cell
      lines, FCR-3 and ITO4 (a cell line with elevated ICAM-1 adherence), was studied
      using CHO cells transfected with CD36 or ICAM-1 receptors as target cells. ICAM-1
      mediated adherence was found to be relatively pH insensitive, whereas CD36
      mediated adherence was pH sensitive and inhibited by monoclonal antibodies and
      peptides based on a region found in human band 3 protein and named pfalhesin.
      Immobilized pfalhesin was used as an affinity matrix to purify CD36 from extracts
      of C32 amelanotic melanoma cells, which have ICAM-1 as well as CD36 receptors,
      and bind both parasite cell lines. We conclude that pfalhesin and CD36 constitute
      an adhesin/receptor pair.

PMID- 7509757
TI  - New insights into the auxiliary domains of eukaryotic RNA binding proteins.
AB  - Eukaryotic RNA binding proteins (RBP) are key players in RNA processing and in
      post-transcriptional regulation of gene expression. By interacting with RNA and
      other factors and by modulating the RNA structure, they promote the assembly of a
      great variety of specific ribonucleoprotein complexes. Many RBPs are composed of
      highly structured and conserved RNA binding domains (RBD) linked to unstructured
      and divergent auxiliary domains; such modular structure can account for a
      multiplicity of interactions. In this context, the auxiliary domains emerge as
      essential partners of the RBDs in both RNA binding and functional specialisation.
      Moreover, the determinants of biologically important functions, such as strand
      annealing, protein-protein interactions, nuclear localization and activity in in
      vitro splicing, seem to reside in the auxiliary domains. The structural and
      functional properties of these domains suggest their possible derivation from
      ancestral non-specific RNA binding polypeptides.

PMID- 7509755
TI  - Correlation between esterase electrophoretic polymorphism and virulence
      associated traits in extra-intestinal invasive strains of Escherichia coli.
AB  - The electrophoretic variations of carboxylesterase B and of esterases A, C and I,
      the presence of mannose resistant haemagglutinin, alpha-haemolysin, cytotoxic
      necrotizing factor type 1 (CNF1) and certain O antigens were compared in 150
      strains of Escherichia coli responsible for extra-intestinal infections.
      Electrophoretic mobilities of outer membrane proteins (OMP) were also studied for
      strains belonging to O4, O6, O7, O8 and O75 serogroups. Fast migrating allozymes
      of carboxylesterase B (pattern B1) were correlated with slow migrating allozymes
      of esterase C, serogroups O7 and O8, lack of virulence factor, and particular OMP
      patterns, whereas slow migrating allozymes of carboxylesterase B (pattern B2)
      were correlated with fast migrating allozymes of esterase C, serogroups O2, O4,
      O6, O18 and O75, virulence factor production, and distinct OMP patterns.
      Allozymes of esterases A and I were not clearly correlated with the distribution
      of virulence factors. The pattern B2 was more strongly associated with CNF1 than
      with alpha-haemolysin and mannose resistant haemagglutinin. These results
      substantiate the view that the electrophoretic pattern B2 of carboxylesterase B
      identified most of the highly pathogenic strains implicated in extra-intestinal
      infection of humans.

PMID- 7509758
TI  - Evidence for the involvement of protein phosphorylation in cyclic AMP-mediated
      amylase exocytosis from parotid acinar cells.
AB  - We evaluated the role of protein phosphorylation in cAMP-mediated amylase
      exocytosis from parotid acinar cells by using H89, a new protein kinase A (PKA)
      inhibitor, which is more lipophilic and 25 times more potent than H8. In our
      previous studies, H8 markedly inhibited protein phosphorylation without
      decreasing amylase release [Takuma, T. (1988) Biochem. J. 256, 867-871]. These
      findings were completely reproduced even in the small acini that were prepared by
      trypsin treatment before collagenase digestion. In the present study, however,
      H89 strongly inhibited both amylase release and protein phosphorylation in a dose
      dependent manner. The inhibitory effect was specific for PKA at least up to 33
      microM, since 33 microM H89 did not block amylase release stimulated by PMA. H85,
      a closely related compound of H89 without inhibitory effect on PKA, did not
      prevent amylase release or protein phosphorylation at least up to 33 microM.
      These results suggest that protein phosphorylation by PKA is involved in cAMP
      mediated amylase exocytosis. The inhibition of protein phosphorylation by H8
      might be insufficient or inadequate for blocking of amylase release.

PMID- 7509760
TI  - ATP-dependent ionic permeability on nuclear envelope in in situ nuclei of Xenopus
      oocytes.
AB  - The nuclear envelope represents a structural and functional barrier between
      cytoplasm and nucleoplasm. Small molecules and solutes passively cross the
      nuclear envelope, whereas the transport of large proteins and RNA requires
      metabolic energy. Using in situ Xenopus oocyte nuclei, we characterized ATP
      dependent ionic permeabilities on the external surface of the envelope. The
      presence, but not necessarily the hydrolysis, of ATP is crucial to maintaining
      the channels in an open state. Localization of the ionic channels is still
      unclear. From morphologic and current kinetics data, we suggest a relation
      between the ionic channels and the nuclear pores. We try, in this way, to explain
      the apparent contradiction between the presence of ion-selective channels in
      parallel with large aqueous pores on the nuclear envelope. Under this hypothesis,
      variations in the metabolic energy content of the cytoplasm would induce
      nucleocytoplasmic passive exchanges. The distribution and movement of charged
      particles across the nuclear envelope may influence many cytoplasmic functions.
      Regulation of the current by ATP could play an important role in hormonal
      stimulation, divalent ion permeation into the nucleus, and cell cycle mechanisms.

PMID- 7509759
TI  - Diagnosis of intrauterine and ectopic pregnancy at 5-7 postmenstrual weeks.
AB  - OBJECTIVES: The potential of the combined use of vaginosonography and serum beta
      hCG levels for early diagnosis of intrauterine and ectopic pregnancies (5-7 weeks
      postmenstrual) was investigated in a multicentric study. METHODS: Three hundred
      and forty-nine patients underwent vaginosonographic examination and determination
      of serum beta-hCG. When the first examination failed in establishing a precise
      diagnosis, repeat examinations were performed on alternate days. RESULTS: During
      the first 3 weeks after the missed menses, vaginosonography can detect
      practically all viable intrauterine pregnancies, half of the nonviable
      intrauterine and viable ectopic pregnancies, and one quarter of nonviable ectopic
      pregnancies, respectively. It was not possible to differentiate intrauterine and
      ectopic pregnancies by serum beta-hCG levels. CONCLUSIONS: Vaginosonographic
      screening, ideally at 2 weeks after the missed menses, permits detection,
      localization, and dating in 80%-90% of suspected pregnancies.

PMID- 7509761
TI  - Nitric oxide and human skin blood flow responses to acetylcholine and ultraviolet
      light.
AB  - Nitric oxide (NO) is a potent endogenous vasodilator of large blood vessels but
      its role in the physiological and pathological control of the human
      microcirculation is not known. This study was designed to assess whether NO
      contributes to the control of blood flow in the human skin microcirculation in
      vivo. Local changes in blood flow were measured in the forearm skin
      microcirculation of normal volunteers. The responses to agents injected
      intradermally were assessed with a laser Doppler flow probe. NO was generated in
      local areas of skin by the injection of the NO donor, sodium nitroprusside.
      Endogenous NO was generated by the injection of acetylcholine and the exposure of
      skin to ultraviolet light (UVB) to stimulate the constitutive and inducible forms
      of nitric oxide synthase (NOS), respectively. The skin microvasculature was
      comparatively insensitive to exogenous NO derived from the NO donor sodium
      nitroprusside, being 10,000-fold more sensitive to the vasodilator prostaglandin
      PGE2 (P < 0.001). However, the rapid onset, dose-dependent local vasodilation
      caused by acetylcholine was blocked by the NOS inhibitor NG-monomethyl-L
      arginine, L-NMMA (P < 0.05), but not by the cyclooxygenase inhibitor
      indomethacin. The delayed local blood flow response to UVB was attenuated by
      either L-NMMA or indomethacin (P < 0.05 in each case). The UVB response was
      abolished by a combination of L-NMMA and indomethacin or by local, topical
      corticosteroid treatment (P < 0.01 in each case). This study indicates that NO
      increases blood flow in the human microcirculation in vivo. NOS inhibition
      attenuated both the rapid blood flow response to acetylcholine and the delayed
      response to UVB. Both NOS and cyclooxygenase contributed to the erythema response
      to UVB, and dual inhibition of both enzymes would explain the mechanism of action
      of the corticosteroid in this model of inflammation.

PMID- 7509763
TI  - Distorted microangioarchitecture and impaired angiogenesis in gastric mucosa of
      portal hypertensive rats.
AB  - BACKGROUND/AIMS: Portal hypertensive (PHT) gastropathy is now recognized as a
      distinct entity, but the size of microvessels has been a subject of controversy.
      Angiogenesis in PHT gastric mucosa has not been explored. The aim of this study
      was to examine the angioarchitecture of PHT and non-PHT gastric mucosae before
      and after ethanol-induced injury utilizing microvascular cast techniques.
      METHODS: Portal hypertension was produced by staged portal vein occlusion.
      Fourteen days later, gastric vascular casts were made in both PHT and control
      (sham-operated) rats by Mercox resin infusion. After tissue dissolution, casts
      were examined under a scanning electron microscope. To examine angiogenesis in
      injured gastric mucosa, the above study was repeated in PHT and control rats 18
      hours after intragastric administration of 100% ethanol. RESULTS: The capillary
      casts in PHT gastric mucosa (mean diameter, 6.3 +/- 0.03 microns) were
      significantly narrower than those of controls (mean diameter, 8.6 +/- 0.02
      microns; P < 0.01). After ethanol injury, 5.5% +/- 0.3% of microvessels in
      gastric mucosa of sham-operated rats contained buds, showing angiogenesis. In
      contrast, PHT gastric mucosa had a paucity of capillary angiogenesis (buds in
      only 0.4% +/- 0.2% of microvessels; P < 0.01 vs. control). CONCLUSIONS: This
      study shows prominent persistent abnormalities in the microangioarchitecture of
      PHT gastric mucosa. Moreover, PHT gastric mucosal microvessels have a marked
      impairment of angiogenic response to ethanol injury.

PMID- 7509762
TI  - [The allorhythmic distribution of ectopic ventricular beats. Observations on the
      electrogenesis and dynamics of concealed ventricular extrasystole].
AB  - BACKGROUND: A regular distribution of ventricular ectopic beats is thought to be
      a relatively uncommon phenomenon, known as "concealed extrasystole". Several
      experimental studies suggest that the phenomenon originates from a "protected"
      ventricular focus. The aim of the present study was to evaluate the 24-hour ECG
      monitoring incidence of ventricular concealed extrasystole in patients with
      highly frequent ventricular ectopic beats, looking for signs useful in
      postulating the electrogenesis of the arrhythmia. METHODS: The 24-hour ECGs of 10
      patients (pts) with highly frequent ventricular extrasystoles were analysed,
      searching for significant sequences in the distribution of ectopic beats (i.e.,
      ectopic beats separated by a number of interectopic sinus beats fulfilling one of
      the formulas of concealed extrasystole). RESULTS: Five cases (50%) showed an
      allorhythmic distribution resulting in a prevalent pattern of concealed bigeminy
      (2n-1) in 3 cases, and concealed trigeminy (3n-1) in 2 cases. The phenomenon,
      however, showed a dynamic behaviour, alternating the distributions from patterns
      of concealed bigeminy to concealed trigeminy or less common patterns, and vice
      versa. The evidence of the pure ectopic cycle and mathematically related
      interectopic intervals in 2 cases, the variability of coupling intervals, and the
      presence of fusion beats in the remaining 3 cases, strongly suggests a
      parasystolic origin of the phenomenon. CONCLUSIONS: The results suggest the
      following: Concealed extrasystole is a relatively common phenomenon, at least in
      patients with highly frequent ventricular extrasystoles; the phenomenon, however,
      is somewhat underestimated due to prevalent quantitative, instead of qualitative,
      Holter monitoring analyses. Among patients with allorhythmically distributed
      ventricular extrasystoles, none showed only one pattern of distribution. In fact,
      each single patient showed two or more patterns throughout the 24-hour
      recordings. Changes from one pattern to another is governed by several factors,
      such as sinus heart rate and/or the influence of electrotonic "modulation" upon
      the ectopic focus. Ventricular extrasystoles with regular allorhythmic
      distribution show a significantly higher variability of coupling intervals than
      the others (p = 0.005).

PMID- 7509764
TI  - Influence of inflammation and atrophy on pancreatic secretory trypsin inhibitor
      levels within the gastric mucosa.
AB  - BACKGROUND/AIMS: Gastrointestinal epithelia contain a powerful protease inhibitor
      called pancreatic secretory trypsin inhibitor (PSTI). Gastric mucus obtained from
      patients with atrophic gastritis or gastric ulceration shows changes suggestive
      of excessive proteolytic digestion. Therefore, the aim of this study was to
      examine whether mucosal PSTI levels are affected by gastritis and/or ulceration.
      METHODS: Mucosal PSTI levels were measured in 12 patients with normal gastric
      histology and 26 patients with gastritis and/or gastric ulceration. RESULTS: In
      control subjects, mean gastric PSTI concentrations were 990 ng/mg protein (95%
      confidence interval, 819-1195) in the antrum and 445 ng/mg protein (95%
      confidence interval, 395-502) in the body. Immunostaining for PSTI was strongly
      positive in the pyloric glands of the antrum and in the foveolar/surface and
      mucus neck cells of the gastric body. Tissue levels of PSTI were reduced by 40%
      in biopsy specimens showing superficial gastritis (P = 0.035) and by 75% in
      biopsy specimens showing atrophic gastritis and/or gastric ulceration (P <
      0.001). Immunostaining was also reduced in specimens showing atrophic gastritis.
      CONCLUSIONS: The decrease in tissue PSTI levels associated with gastric atrophy
      probably represents a permanent reduction in one of the mucosal defense
      mechanisms. This may lead to the maintenance and even expansion of the gastritic
      process with time.

PMID- 7509766
TI  - [Antibodies against Escherichia coli RecA protein reveal two nuclear proteins in
      bovine spermatocytes which interact with synaptonemal complex structures of
      meiotic chromosomes of various eukaryotic organisms].
AB  - Three RecA-like proteins were detected in bovine meiotic cells using antibodies
      against Escherichia coli RecA protein. After isolation and purification of these
      RecA-like proteins their molecular weights appeared to be equal to 37, 70 and 130
      kD. The 37 kD protein accompanies all the stages of spermatogenesis up to the
      stage of mature spermatozoa. The 70 kD protein is detectable only in nuclei of
      cells at the stage of prophase I of meiotic division. These RecA-like proteins
      are involved in the formation of structural elements of the synaptonemal complex
      (SC) and are detected in the SC composition in meiotic cells not only of mammals
      but also of plants and insects, which suggests the evolutionary conservative
      character of these proteins.

PMID- 7509765
TI  - Central nervous system Whipple's disease: relapse during therapy with
      trimethoprim-sulfamethoxazole and remission with cefixime.
AB  - The central nervous system (CNS) is frequently involved in patients with
      Whipple's disease and is the most common site of disease relapse. Antibiotics
      such as trimethoprim-sulfamethoxazole (TMP-SMX) that have reliable CNS
      penetration, are therefore recommended as first-line therapy. We report a patient
      with Whipple's disease who was treated with TMP-SMX and presented 14 months after
      initiation of therapy with visual decline and severe headaches. The patient was
      also treated concurrently with low-dose weekly methotrexate for severe psoriasis.
      Evaluation by magnetic resonance imaging revealed bilateral posterior white
      matter abnormalities that pathologically were consistent with Whipple's disease.
      He was ultimately treated with cefixime, an orally administered third-generation
      cephalosporin. Visual function improved on this regimen and follow-up magnetic
      resonance imaging showed regression of the lesions. This case represents the
      first report of both CNS relapse during therapy with TMP-SMX and successful
      treatment with cefixime. We also speculate that methotrexate, which impairs cell
      mediated immunity, may have contributed to the relapse.

PMID- 7509768
TI  - Inflammatory mediators and cytokines--new aspects of the pathophysiology and
      assessment of severity of acute pancreatitis?
AB  - Most attacks of acute pancreatitis are mild and self-limiting. In 10-20% of the
      cases, however, severe disease with multiple systemic complications develops.
      During the last few years it has been recognized that activated leukocytes have
      an important role in the multisystem involvement during acute pancreatitis.
      Activated leukocytes are thus a pathogenetic factor in the severity of the
      disease. Activation of polymorphonuclear granulocytes (PMNs) and of
      monocytes/macrophages is an early event during severe acute pancreatitis. Factors
      released by activated leukocytes therefore reflect the severity of the disease.
      Three independent studies have shown that released PMN-elastase is a reliable
      early prognostic marker that permits correct classification of 80-95% of the
      patients within the first 24-48 hours. Interleukin-6 (IL-6), mainly secreted by
      activated monocytes/macrophages, is also an early prognostic parameter (shown in
      one study), but is not superior to PMN-elastase. Leukocyte activation markers are
      more reliable than multiple scoring systems in the assessment of the severity of
      acute pancreatitis. Compared with PMN-elastase or IL-6, increased plasma
      concentrations of such acute-phase proteins as alpha-1-antitrypsin or CRP, and
      consumption of the protease inhibitor alpha-2-macroglobulin, are later events
      that can be detected only 1 to 4 days later. Comparison of the various
      inflammatory parameters suggests that PMN-elastase is the best early and reliable
      prognostic marker in acute pancreatitis. The reviewed data underscore the role of
      activated leukocytes in the pathogenesis of complicated acute pancreatitis.

PMID- 7509769
TI  - Clinical significance of concomitant hepatitis C infection in patients with
      alcoholic liver disease.
AB  - The significance of antibodies to hepatitis C virus in patients with chronic
      alcoholic liver disease is unclear. Prior studies have utilized the first
      generation enzyme-linked immunosorbent assay, which is limited by problems with
      sensitivity and specificity. Hepatitis C virus infection in 137 patients with
      biopsy-proven alcoholic liver disease was assessed with second-generation
      hepatitis C virus antibody assays and reverse transcription-polymerase chain
      reaction for detection of hepatitis C virus RNA in the serum. The patients were
      categorized into three groups according to results of serological testing.
      Discriminant-function analysis was used to determine which factors (risk,
      biochemical and histological) could best differentiate the three groups. Thirty
      three patients were reactive on second-generation enzyme-linked immunosorbent
      assay/second-generation recombinant immunoblot assay and RNA positive (group 1).
      Twelve were reactive on second-generation enzyme-linked immunosorbent
      assay/second-generation recombinant immunoblot assay but RNA negative (group 2).
      Eighty-six were nonreactive on second-generation enzyme-linked immunosorbent
      assay, and six were reactive on second-generation enzyme-linked immunosorbent
      assay but negative on second-generation recombinant immunoblot assay and negative
      for hepatitis C virus RNA (group 3). Seventy-six percent of patients in group 1
      and 58% in group 2 had parenteral risk factors, compared with only 1% in group 3
      (p < 0.00001). The mean ALT level was higher in group 1 patients (p < 0.05). The
      mean histologic activity index was significantly higher in group 1 (p =
      0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509767
TI  - The HNK-1 epitope in the inner connective tissue layer of the human ciliary body
      in exfoliation syndrome and various types of glaucoma.
AB  - Possible changes in the expression of the HNK-1 carbohydrate epitope in the inner
      connective tissue layer of the human ciliary body, located between the ciliary
      epithelium and muscle, was studied using 2 formalin-fixed, paraffin-embedded eyes
      with exfoliation syndrome, 33 eyes with different types of glaucoma, and 21
      morphologically normal control eyes. A strong immunoreaction delineating cell
      process was observed in this layer with monoclonal antibodies HNK-1 and VC1.1
      recognizing the HNK-1 epitope in control specimens, whereas partly granular
      immunoreaction was present in eyes with exfoliation syndrome. Exfoliation
      material was also immunoreactive. In all types of advanced glaucoma, the
      immunoreaction was mostly granular in nature and greatly diminished. No
      difference in HNK-1 immunoreactivity between control and glaucoma eyes was seen
      in the retina and ciliary epithelium. Elevated intraocular pressure, either
      directly or by decreasing blood flow to the ciliary body, may cause degenerative
      or metabolic changes in the inner connective tissue layer cells that bear or
      secrete molecules sharing the HNK-1 epitope. The partly granular immunoreactivity
      in eyes with exfoliation syndrome only indicates changes in this epitope even
      without an increase in intraocular pressure.

PMID- 7509770
TI  - Endothelial activation and circulating vascular adhesion molecules in alcoholic
      liver disease.
AB  - Alcoholic hepatitis is characterized by hepatocyte necrosis associated with
      infiltration of the liver parenchyma by neutrophils. The mechanisms responsible
      for recruiting neutrophils to the liver are unknown. We report high circulating
      levels and tissue expression of the endothelial adhesion molecule E-selectin in
      alcoholic hepatitis. Because expression of E-selectin is involved in neutrophil
      transmigration into inflamed tissue, it may play a crucial role in the
      recruitment of neutrophils to the liver in alcoholic hepatitis. By contrast, we
      detected high levels of vascular cell adhesion molecule-1, the endothelial
      counter-receptor for the lymphocyte adhesion molecule very late antigen-4, in
      alcoholic cirrhosis, which is associated with a predominantly mononuclear cell
      infiltrate. Both diseases were associated with high levels of circulating
      intercellular adhesion molecule-1, which is released by activated lymphocytes,
      providing further evidence of immune activation in alcoholic liver disease.

PMID- 7509771
TI  - Structure and localization of the IGFBP-1 gene and its expression during liver
      regeneration.
AB  - Insulin-like growth factor-binding protein-1s are important modulators of the
      insulin-like growth factors that may have both positive and negative effects on
      the ability of insulin-like growth factors to stimulate cell growth. The IGFBP-1
      gene is one of the most highly induced immediate-early genes after partial
      hepatectomy. The IGFBP-1 gene is also expressed at a high level during fetal
      liver development and in response to nutritional changes and diabetes. Therefore
      it may have important roles in liver growth and metabolism. To begin to examine
      the regulation of this gene, we cloned and sequenced the entire mouse IGFBP-1
      gene. Its structure is highly similar to that of the human gene, and, in addition
      to the exonic regions, the two genes are highly conserved in specific regions in
      the promoter and first intron. Analysis of this conservation allows us to predict
      important regulatory sites that define the tissue specific and insulin-mediated
      regulation of the gene and identify potential sites that might be important for
      the transcriptional induction during liver regeneration. The mouse gene is
      located on mouse chromosome 11; it is found at the boundary between regions in
      the mouse genome homologous to human chromosomes 22 and 7. We found IGFBP-1 mRNA
      in both parenchymal and nonparenchymal RNA after partial hepatectomy. Using in
      situ hybridization of IGFBP-1 mRNA in regenerating rat liver tissue, we
      demonstrated IGFBP-1 transcripts in several cell types. We found that IGFBP-1
      gene induction after partial hepatectomy is paralleled by protein
      expression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509772
TI  - Immunohistochemical study of hepatic fibrosis induced in rats by multiple
      galactosamine injections.
AB  - Multiple injections of D-galactosamine induce liver fibrosis and cirrhosis in
      rats. The purpose of this immunopathological study was to correlate inflammation
      and hepatic extracellular matrix remodeling after repeated administration of
      galactosamine. Rats were given 10, 20, 30, 40, 60, 80, 100 and 140
      intraperitoneal injections of D-galactosamine (500 mg/kg body wt, three times
      weekly). Controls received injections of saline solution. Cryostat sections of
      liver tissue obtained on biopsy or autopsy were immunostained with a panel of
      monoclonal and polyclonal monospecific antibodies reactive with macrophages, T
      and B lymphocytes, desmin, the extracellular matrix components fibronectin;
      laminin; collagen types I, III and IV; and the fibronectin receptor alpha 5 beta
      1. Total RNA was extracted and Northern-blot analysis was performed with a
      specific cDNA probe for rat collagen type III. Spotty liver cell necrosis and
      mild portal and parenchymal inflammation was seen after 10 injections of
      galactosamine. After 20 to 40 injections, expansion of protal tracts, prominent
      bile ductular proliferation and gradual formation of fibrous septa were
      encountered with the development of cirrhosis at later intervals. These
      progressive histological changes were paralleled by a gradual increase of desmin
      positive cells in developing septa with deposition of fibronectin; collagen types
      I, III, and IV; and laminin. Northern-blot analysis showed that this accumulation
      of extracellular matrix was not accompanied by increase of mRNA for collagen type
      III. In conclusion, repetitive administration of galactosamine causes progressive
      liver disease with prominent bile ductule proliferation and development of
      fibrous septa. These pathological alterations bear some resemblance to the
      morphological changes in chronic biliary disease in human beings.

PMID- 7509773
TI  - Just say "NO" to viral hepatitis?

PMID- 7509774
TI  - Paneth cell-like change in prostatic adenocarcinoma represents neuroendocrine
      differentiation: report of 30 cases.
AB  - Paneth cell-like change (PCLC) of the prostatic epithelium is considered to be a
      distinct form of neuroendocrine differentiation characterized by isolated cells
      or small groups of cells with prominent eosinophilic cytoplasmic granules. We
      evaluated 300 serially sectioned radical prostatectomy specimens from patients
      with prostatic adenocarcinoma who had not received prior adjuvant therapy
      (pathologic stages T2NOMO [177 patients], T3NOMO [100 patients], and TxN1MO [23
      patients]). Paneth cell-like change was identified in 30 cases (10%), ranging
      from 1 to 20 high-power fields/positive case (mean, 4.1 high-power fields/case).
      There was no correlation of PCLC with prostate volume, prostate weight, Gleason
      grade, nuclear grade, lymph node metastases, serum prostate-specific antigen
      levels, cancer volume, area or presence of capsular perforation, seminal vesicle
      invasion, or glandular mucin (all P > .05), although a positive correlation was
      seen with cribriform pattern (r = 0.50, P = .0015). Immunohistochemistry revealed
      cytoplasmic immunoreactivity within cells of PCLC for chromogranin (seven of
      seven cases), neuron-specific enolase (seven of seven cases), serotonin (six of
      seven cases), prostate-specific antigen (five of seven cases), and prostatic acid
      phosphatase (four of seven cases); lysozyme was negative (seven cases). Our
      findings indicate that PCLC is more common than previously reported, but that it
      is not associated with tumor grade, serum PSA levels, or pathologic stage. This
      study also shows that PCLC represents neuroendocrine differentiation, suggesting
      that the term "Paneth cell-like change" be deleted from the pathologist's lexicon
      in relation to prostatic adenocarcinoma; a more appropriate term might be
      "neuroendocrine cells with large eosinophilic granules."

PMID- 7509775
TI  - Mouse Cd7 maps to chromosome 11.

PMID- 7509776
TI  - Increased mutagen sensitivity in head-and-neck squamous-cell carcinoma patients,
      particularly those with multiple primary tumors.
AB  - Mutagen sensitivity is a constitutional factor which may be used to identify head
      and-neck squamous-cell carcinoma (HNSCC) patients at high risk for the
      development of multiple primary tumors (MPT). In this retrospective study,
      mutagen sensitivity was measured in HNSCC patients with a single primary tumor
      (SPT), HNSCC patients who have already developed MPT and control subjects with no
      tumor history. In vitro, lymphocytes were challenged with bleomycin and
      chromosomal damage was quantified by scoring chromatid breaks of 100 cells. A
      significant difference in the mean number of breaks per cell (b/c) was found
      between SPT patients and controls. Patients with MPT showed a significantly
      higher mean b/c value than SPT patients. This increase in mutagen sensitivity in
      HNSCC patients was not related to well-known cancer risk factors such as age, or
      life-style factors such as smoking and alcohol drinking habits. In addition,
      tumor site but not tumor stage was found to be related to mutagen sensitivity. On
      the basis of our findings, we propose that mutagen sensitivity is not an
      independent risk factor but a constitutional factor which reflects the way in
      which genotoxic compounds are dealt with and is thereby directly related to
      cancer risk.

PMID- 7509777
TI  - RT-PCR detection of fibronectin EDA+ and EDB+ mRNA isoforms: molecular markers
      for hepatocellular carcinoma.
AB  - Alternative splicing of fibronectin pre-mRNA has been shown to be independently
      regulated at the EDA and EDB regions in a tissue and developmental stage-specific
      manner. In this study, RT-PCR approaches were developed for the detection of EDA
      and EDB FN mRNA isoforms in hepatocarcinoma cells (SK-Hep-I) grown in vitro and
      in human liver biopsies. While EDA+ and EDB+ isoforms were not present in control
      adult liver, they were detectable in the hepatocarcinoma cells and in fetal
      liver. The RT-PCR analysis, extended to biopsies of malignant and non-malignant
      hepatic tissues, showed that FN mRNAs containing the EDA and EDB sequences were
      present in the 14 hepatocellular carcinomas (HCCs) tested but absent in the non
      tumorous liver tissues (i.e., normal parenchyma, non-specific reactive and
      chronic hepatitis, steatosis). The EDB+ FN mRNA isoforms were also detected in 3
      cases of benign neoplasm (hepatocellular adenoma, HCA, I; nodular focal
      hyperplasia, NFH, 2), while the EDA+ was only detectable in I of the 2 cases of
      NFH. In addition, both EDA+ and EDB+ isoforms were expressed in 5 out of 9
      cirrhotic livers surrounding the tumors. This molecular analysis, which can also
      be performed on small liver biopsies (2 mg), may therefore be a useful additional
      tool in the diagnosis of HCC.

PMID- 7509778
TI  - Expression of cytokine/growth factors and their receptors in human melanoma and
      melanocytes.
AB  - Human tumors can constitutively express cytokines and growth factors, but the
      extent of this expression has not been investigated. Using 44 different probes to
      cytokines, growth factors, and their receptors, we tested 21 melanoma and 5
      melanocyte cultures for RNA transcript expression by reverse transcriptase
      polymerase chain reaction. With 30 amplification cycles, expression of the
      cytokines interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), IL-7,
      gro alpha, IL-8 and the p35 chain of IL-12 was detected in more than 60% of
      melanomas. Concomitant receptors for IL-6 and IL-7 were also detected. IL-1
      alpha, IL-5, Rantes, IL-10, interferon (IFN)-beta, tumor-necrosis factor (TNF)
      alpha, G-colony-stimulating factor (CSF) and GM-CSF were expressed at lower
      levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only gro
      alpha was consistently detected. No expression of IL-2, IL-3, IL-4, IL-9, the p40
      chain of IL-12, IFN-alpha or IFN-gamma RNA transcripts was detected in melanomas
      or melanocytes. The growth factors expressed by melanomas and, after further
      signal amplification, by melanocytes were transforming growth factor (TGF)-alpha,
      epidermal growth factor (EGF), TGF-beta, endothelial-cell growth factor (ECGF),
      basic-fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The
      receptors EGFR, FGFR, NGFRp70 and c-kit were also expressed by melanomas and
      melanocytes. These results point to new possible autocrine and paracrine pathways
      in melanoma biology.

PMID- 7509779
TI  - Expression and function of the insulin-like growth factor I system in human non
      small-cell lung cancer and normal lung cell lines.
AB  - In order to analyze the presence and the function of the "insulin-like growth
      factor I (IGF-I) system" in human non-small-cell lung cancer (N-SCLC) we tested 5
      cell lines of different histological sub-types: A549, Ca-Lu-6, SK-Lu-1
      (adenocarcinoma); Ca-Lu-1, SK-Mes-1 (squamous carcinoma) and one normal
      fibroblast-like fetal lung cell line (IMR-90) for expression of the IGF-I peptide
      and its RNA transcribed from the IGF-I gene; IGF-binding proteins (IGF-BP); IGF-I
      receptor (IGF-I-R) and its mRNA. In addition, we examined the capacity of
      exogenous human recombinant IGF-I to enhance the in vitro cell proliferation. In
      medium conditioned from cell cultures, we detected immunoreactive IGF-I material
      by radioimmunoassay. Western ligand blot and affinity labelling demonstrated the
      presence of several molecular species of IGF-BPs (IGF-BP-4, -1, -2, -3) as well.
      Northern blot analysis of polyA+ RNA from all cell lines examined revealed the
      presence of IGF-I and IGF-I-R mRNA. Moreover, binding studies on cultured cell
      lines showed one class of high-affinity, operative type-I IGF cell-surface
      binding sites. Finally, by thymidine uptake and colorimetric metabolic MTT
      assays, we found that most neoplastic cell lines react mitogenically to IGF-I and
      that its physiological effect is abolished by an anti-IGF-I-receptor antibody.
      These data indicate the importance of the IGF-I system in N-SCLC growth.
      Furthermore, they suggest that this mitogenic complex should be appraised as a
      possible target for anti-neoplastic drugs, antibodies or growth-factor analogues
      offering potential new approaches to therapy.

PMID- 7509780
TI  - Cell differentiation: an evolutionary perspective.

PMID- 7509781
TI  - Molecular and cellular aspects of neurotransmission and neuromodulation.

PMID- 7509782
TI  - [Balloon dilatation vs. prostatic transurethral resection in stages I-II
      prostatic adenoma].
AB  - Thirty consecutive patients with benign prostatic hypertrophy St. I-II (adenom
      weight < 25g) were treated either by balloon dilatation (Group I) or
      transurethral resection (group II). Peak flow, residual urine and voided urine
      did not improve after balloon dilatation in a follow-up of 9 months. In contrast
      peak flow enhanced after TUR-P from 10.4 ml/sec. to 21.9 ml/sec. Residual urine
      reduced from 65 ml to 30. In group I obstructive symptom score (6.1 > 4.5) and
      irritative symptom score (5.5 > 3.6) decreased after 9 months, TUR-P resulted in
      a greater reduction of obstructive score (7.4 > 1.6) and irritative score (6.0 >
      2.4). This study with selected patients does not support indications for balloon
      dilatation.

PMID- 7509783
TI  - [Endocrinology and fertility in stage I testicular tumor].
AB  - The situation of endocrinology and fertility of patients suffering from
      testicular cancer stage I (Peckham) with good survival rates were evaluated
      before semicastration. The value of beta-hCG is of great importance. According to
      this criteria 3 groups were formed. beta-hCG positive tumors, beta-hCG positive
      tumors out of the blood sample of the vena spermatica after ablation of the
      testis tumor and beta-hCG negative tumors. The histology is of secondary
      importance. 54 patients with testicular cancer were evaluated in this study. From
      37 patients it was possible to get a spermiogram before semicastration. For the
      analysis of the spermiogram the values of LH, FSH, Testosterone and E2 are
      responsible. The values of beta-hCG in the serum from the periphery is of great
      importance, while a single elevation of beta-hCG in the serum out of the
      v.spermatica does not change the endocrinology. The question of kryosperm
      conservation is according to these parameters better evaluable.

PMID- 7509785
TI  - An assessment of ethical sensitivity: implications for interdisciplinary
      education.
AB  - The purpose of this study was to examine the relationship between discipline
      specific knowledge and ethical sensitivity among health professions students, as
      related to different levels of education. Specifically, the study addressed the
      question, do health professions students, grouped according to their disciplines
      and levels of education, differ in their ethical sensitivity to selected
      discipline-specific ethical dilemmas? Subjects included 48 senior students from
      the disciplines of dental assisting, dental hygiene, and dentistry, and the
      disciplines of surgical technology, respiratory therapy, and medicine. Dental and
      nondental disciplinary groups represented the certificate, associate degree, and
      graduate levels of education. Differences between and among groups' ethical
      sensitivity scores, as derived from the Dental Ethical Sensitivity Test (DEST),
      were statistically analyzed. Results of the study indicated that, given dental
      related case studies, students with discipline-specific knowledge in dentistry
      did not differ in ethical sensitivity from students who did not possess
      discipline-specific knowledge in that field. However, the results also
      demonstrated that students enrolled at different levels of education did differ
      significantly in ethical sensitivity, regardless of discipline-specific knowledge
      in dentistry. These findings have implications for teaching applied professional
      ethics in health professions education, from an interdisciplinary perspective.

PMID- 7509784
TI  - [Can administration of trasylol in reduced Hammersmith dosage with simultaneous
      transfusion of autologous blood meet the requirements of open heart surgery?].
AB  - PROBLEM: The general positive effect of the proteinase inhibitor trasylol on
      blood loss and transfusion demand in cardiac surgery has been demonstrated in
      several placebo-controlled studies. Given the possibility of cardiac and renal
      side effects associated with a high dose of trasylol (Hammersmith dosage: 6 x
      10(6) kallikrein inactivator units KIU), the question of a dose reduction was
      raised. METHODS: Being designed as a randomized double-blind comparative group
      study, the investigation included 120 patients with elective primary cardiac
      surgery from November 1990 to April 1992. One characteristic aspect of this study
      was the combined administration of trasylol and autologous blood transfusions. To
      compare the efficacy and safety of different doses of trasylol, two groups, each
      with 60 patients, were created: the former with the full Hammersmith dose (high
      dose group = HD group), the latter with half of the Hammersmith dose (los dose
      group = LD group). A placebo group had to be excluded for ethical reasons.
      RESULTS: The trasylol plasma levels showed a good dose correlation for the
      complete interval. The intra-operative bleeding tendency, as judged by the
      surgeons in charge, did not show any statistical significant difference between
      the HD group and the LD group. As to the post-operative blood loss via thoracic
      drainage, the early collection periods did not show any difference between both
      study groups. Starting at 6 hours post-operatively, the drainage losses showed a
      tendency towards lower volumes in the HD group. This difference was statistically
      significant for the time period "6-12 hours post-operatively". The analysis of
      the post-operative complications did not show any difference. SUMMARY: In this
      study with a high percentage of autologous blood transfusions, a lower dose of
      trasylol seemed to be nearly as effective as a full Hammersmith dose. However,
      such a reduced dose did not demonstrate any advantage regarding the complication
      rate in comparison with the conventional high dose.

PMID- 7509786
TI  - Hispidospermidin, a novel phospholipase C inhibitor produced by Chaetosphaeronema
      hispidulum (Cda) Moesz NR 7127. I. Screening, taxonomy, and fermentation.
AB  - A novel phospholipase C inhibitor, hispidospermidin, was discovered from a fungal
      culture broth. The producing fungus, NR 7127, formed abundant pycnidia on banana
      leaf agar under near UV light. The ostiolate pycnidia were dark colored with a
      short beak possessing numerous protruding setae. The conidiogeneous cells were
      phialidic. The conidia were hyaline, 1 septate, smooth and spindle-shaped. From
      these distinctive characteristics, this strain was identified as
      Chaetosphaeronema hispidulum (Cda) Moesz of the Coelomycetes. Hispidospermidin
      was produced in a 50-liter jar fermentor containing 2% glucose, 2% potato starch,
      2% Toast soya, 0.5% yeast extract, 0.25% NaCl, 0.0005% ZnSO4.7H2O, 0.0005%
      CuSO4.5H2O, 0.0005% MnSO4.4H2O, 0.32% CaCO3, and 0.3% Nissan disfoam CA-115.
      Fermentation was conducted at 27 degrees C at an aeration rate of 30
      liters/minute and agitated at 500 rpm for 95 hours. Maximum production yield of
      hispidospermidin was observed after 72 hours. Hispidospermidin inhibited rat
      brain phospholipase C at 16 microM of IC50. This is the first recorded discovery
      of a secondary metabolite from the genus Chaetosphaeronema.

PMID- 7509787
TI  - Hispidospermidin, a novel phospholipase C inhibitor produced by Chaetosphaeronema
      hispidulum (Cda) Moesz NR 7127. II. Isolation, characterization and structural
      elucidation.
AB  - Hispidospermidin (1) is a novel phospholipase C inhibitor produced by
      Chaetosphaeronema hispidulum (Cda) Moesz NR 7127. Its structure (C25H47N3O) has
      been elucidated as a cage compound with a trimethylspermidine side chain based on
      various NMR studies, including 1H-1H COSY, 13C-1H COSY, HOHAHA, HMBC, COLOC and
      long range J C-H resolved 2D spectroscopy. The absolute configuration of 1 has
      been elucidated by modified Mosher's method on the (R)- and (S)-MTPA amides of a
      derivative of 1.

PMID- 7509789
TI  - Molecular cloning of a mercurial-insensitive water channel expressed in selected
      water-transporting tissues.
AB  - Two mercurial-inhibitable water-transporting proteins have been identified:
      CHIP28, an erythrocyte water channel also expressed in kidney tubules and
      selected extrarenal epithelia, and WCH-CD, a kidney collecting duct water
      channel. In searching for a protein responsible for the high transcellular water
      permeability in lung alveolus, we cloned a 32-kDa water channel (mercurial
      insensitive water channel (MIWC)) from a rat lung cDNA library with several novel
      features. Water permeability was strongly increased in Xenopus oocytes expressing
      MIWC in a mercurial-insensitive manner, in contrast to known water channels. By
      in situ hybridization, MIWC showed an unique distribution in cells that do not
      express CHIP28, including kidney papillary vasa recta, cells lining the
      subarachnoid space and ventricles in brain, the inner nuclear layer in retina,
      and the conjunctival epithelium. An alternatively spliced form of MIWC with a 165
      base pair deletion in the coding sequence was also identified; relative
      expression of the spliced mRNA was tissue-specific. The MIWC water channel may
      participate in the urinary concentrating mechanism, the absorption of
      cerebrospinal fluid, and other physiological processes.

PMID- 7509791
TI  - Kinetics of empty store-activated Ca2+ influx in HeLa cells.
AB  - The intracellular Ca2+ indicator Indo-1 was used to monitor changes in cytosolic
      [Ca2+] ([Ca2+]i) in single HeLa cells upon readmission of external Ca2+ after a
      short incubation in Ca(2+)-free solution. HeLa cells were responsive to histamine
      but not to caffeine, and their histamine-sensitive store was totally depleted by
      a 60-min exposure to 2 microM thapsigargin. The resting [Ca2+]i in thapsigargin
      treated cells was higher than in control cells and low amplitude [Ca2+]i
      oscillations were observed in about 20% of the cells. Readmission of external
      Ca2+ after a brief withdrawal of extracellular Ca2+ resulted in a transient
      [Ca2+]i rise, which then decayed to the same elevated [Ca2+]i measured before the
      Ca2+ withdrawal period. The [Ca2+]i rise was associated with an increased rate of
      Mn2+ entry, measured as the rate of quenching of intracellular Fura-2. The same
      procedure did not affect the [Ca2+]i in control cells not pretreated with
      thapsigargin. The amplitude of this [Ca2+]i transient in thapsigargin pretreated
      cells depended on the duration of prior incubation in Ca(2+)-free medium. The
      [Ca2+]i rise induced by elevating the extracellular [Ca2+] from 1.5 to 10 mM was
      more pronounced if the [Ca2+]i during the initial incubation in 1.5 mM Ca2+ was
      first lowered by depolarizing the cells. We conclude that an empty store
      stimulates a Ca2+ entry pathway consisting of two components: a continuously
      elevated basal leak and a second component that is transient due to the high
      [Ca2+]i-induced inhibition of the Ca2+ entry pathway. This inhibition and the
      subsequent recovery from it as the [Ca2+]i is brought to resting levels could
      cause the oscillatory Ca2+ entry that we recorded in a fraction of the
      thapsigargin-treated cells.

PMID- 7509790
TI  - Common tetrasaccharide epitope NeuAc alpha 2-->3Gal beta 1-->3(Neu-Ac alpha 2-
      >6)GalNAc, presented by different carrier glycosylceramides or O-linked peptides,
      is recognized by different antibodies and ligands having distinct specificities.
AB  - A novel globo-series disialoganglioside, disialosyl galactosyl globoside
      (Structure 1 below), defined by new monoclonal antibody (mAb) RM2, was isolated
      and characterized as having terminal structure identical to that of ganglio
      series ganglioside GD1 alpha (Structure 2) and a common mucin-type epitope
      (Structure 3) widely distributed in glycoproteins such as glycophorin A. While
      these three structures share a common nonreducing tetrasaccharide terminus, mAb
      RM2 showed strong specific reactivity only with Structure 1, not with Structures
      2 or 3. Another mAb, QSH2, reacted strongly with Structure 3 but did not cross
      react with Structures 1 or 2. Conformational molecular models based on minimum
      energy hard sphere exoanomeric calculations suggest that Structure 1 presents a
      unique surface topology distinct from that of Structures 2 or 3. Our findings
      suggest the novel concept that reactivity of a common carbohydrate epitope with
      different antibodies or ligands is highly dependent on the type of carrier
      glycosylceramide or carrier O-linked peptide. [formula: see text]

PMID- 7509788
TI  - New albumin gene 3' adjacent to the alpha 1-fetoprotein locus.
AB  - The albumin multigene family encodes proteins synthesized in the liver and
      secreted in the serum to fulfill ligand-carrier functions. The albumin (ALB),
      alpha 1-fetoprotein (AFP), and vitamin D-binding protein genes are syntenic, the
      ALB and AFP genes are organized in tandem, and the AFP gene is selectively
      expressed in the fetal liver. We now report the existence of a fourth member of
      the albumin gene family, located 10 kilobases downstream from the AFP locus. The
      new gene, named alpha-albumin (alpha ALB), is selectively expressed in the liver
      at late stages of development. The alpha ALB mRNA sequence encodes a predicted
      secreted protein with the typical triple domain disulfide cross-linked structure.
      Comparisons of coding and promoter sequences suggest that alpha ALB could be a
      phylogenetic intermediate between the ALB and AFP genes. The developmental switch
      between alpha ALB gene activation and AFP gene repression suggests new regulatory
      interplays at the albumin locus and adult stage-specific ligand binding functions
      carried out by the alpha ALB gene product.

PMID- 7509792
TI  - Molecular cloning of pancreatic group I phospholipase A2 receptor.
AB  - We have recently reported that mammalian pancreatic group I phospholipase A2
      (PLA2-I) has its specific receptor (PLA2 receptor) on a variety of mammalian
      cells and that various biological responses are elicited by PLA2-I via this
      receptor. In this study, we cloned cDNAs encoding a protein corresponding to the
      bovine PLA2 receptor purified from the corpora lutea on the basis of its partial
      amino acid sequences. The identity of a protein encoded by the cloned cDNA with
      the bovine PLA2 receptor was verified by a transient expression experiment using
      COS-7 cells. Interestingly, the deduced primary structure of the PLA2 receptor
      (1,463 amino acid residues) exhibits a close relatedness throughout the molecule
      to that of the macrophage mannose receptor, a unique member of Ca(2+)-dependent
      (C-type) animal lectin family, in spite of their functional diversity. Based on
      this sequence similarity between these two receptors, the domain organization of
      the PLA2 receptor could be tentatively assigned as follows; 10 extracellular
      domains including 8 tandem repeats homologous to C-type carbohydrate-recognition
      domains (CRDs) and a single transmembrane region followed by a short cytoplasmic
      tail. The results of transient expression experiments for mutant PLA2 receptors
      supported this assignment and furthermore suggested the region responsible for
      PLA2-I binding corresponds to CRDs in the mannose receptor.

PMID- 7509793
TI  - Retinoylation of vimentin in the human myeloid leukemia cell line HL60.
AB  - Retinoylation (retinoic acid acylation) is a posttranslational modification of
      proteins occurring in many eukaryotic cell lines. The widespread occurrence of
      retinoylation suggests that it may play a role in many effects of retinoic acid
      (RA) on cells. The regulatory subunits of cyclic AMP-dependent protein kinase are
      retinoylated in the human myeloid leukemia cell line HL60 (Takahashi, N., Liapi,
      C., Anderson, W. B., and Breitman, T. R. (1991) Arch. Biochem. Biophys. 290, 293
      302), and cytokeratins are retinoylated in normal human keratinocytes (Takahashi,
      N., Jetten, A. M., and Breitman, T. R. (1991) Biochem. Biophys. Res. Commun. 180,
      393-400). We show, in this study, that the intermediate filament protein vimentin
      is retinoylated in HL60 cells during a 24-h exposure to 100 nM [3H]RA. We found
      that a retinoylated protein of M(r) 55,000 coeluted on anion exchange
      chromatography and comigrated on either one- or two-dimensional polyacrylamide
      gel electrophoresis with a protein that also was stained on immunoblots by an
      anti-vimentin antibody. About 50% of the [3H]RA was released from this M(r)
      55,000 retinoylated protein after hydrolysis with either NH2OH (1 M, pH 10) or
      CH3OH, 0.1 M KOH. These results indicated that a large fraction of the RA was
      bound to vimentin by an ester bond. Both the M(r) 55,000 retinoylated protein and
      immunoreactive vimentin were associated with cell nuclei isolated by two
      procedures. They were detached during exposure to a nonionic detergent buffer,
      suggesting that they are bound to the nuclear envelope. These results indicate
      that retinoylation is a new modification of vimentin that may be an early event
      in RA-induced differentiation of HL60 cells.

PMID- 7509794
TI  - SH2-dependent association of phosphatidylinositol 3'-kinase 85-kDa regulatory
      subunit with the interleukin-2 receptor beta chain.
AB  - Interleukin-2 (IL-2) signaling results in tyrosine phosphorylation of the 75-kDa
      IL-2 receptor (IL-2R) beta chain and the activation of phosphatidylinositol 3'
      kinase (PI3-K). Herein, we demonstrate that the 85-kDa (p85) regulatory subunit
      of PI3-K physically associates with the tyrosine-phosphorylated IL-2R beta chain.
      A fusion protein containing both the amino- and the carboxyl-terminal src
      homology 2 domains of p85 precipitates an 80-kDa tyrosine-phosphorylated protein
      (pp80) from the lysates of IL-2-stimulated, but not unstimulated, human T
      lymphoblasts. Preclearing studies and immunoblotting with an antiserum to the IL
      2R beta chain demonstrates that pp80 represents a portion of the IL-2R beta chain
      pool. A tyrosine-phosphorylated oligopeptide corresponding to tyrosine 392 of the
      IL-2R beta chain partially inhibits binding of the IL-2R beta chain by p85 fusion
      protein, raising the possibility that this residue plays a role in the
      interaction of PI3-K with the receptor.

PMID- 7509796
TI  - Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85
      subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3
      kinase activity in COS-1 cells.
AB  - The receptor tyrosine kinase c-kit is thought to mediate its diverse effects on
      different cell lineages by association and activation of distinct second
      messenger systems. One of the immediate events after binding of the kit ligand to
      the receptor is its association with the 85-kDa subunit (p85) of the
      phosphatidylinositol (PI) 3-kinase and the activation of the enzyme. In the
      present study, we examined the association and activation of PI 3-kinase with
      mutant forms of the c-kit receptor transiently expressed in COS-1 cells. To
      define the binding site of p85 we substituted the putative tyrosine
      phosphorylation sites in the kinase insert region of the c-kit receptor by
      phenylalanine (YF702, YF719, YF728, and YF745, respectively). The results
      indicate that, upon stimulation of cells with kit ligand, 1) the wild-type c-kit
      protein was readily autophosphorylated and autophosphorylation was not diminished
      significantly with any of the mutant proteins; 2) p85 and PI 3-kinase activity
      associated with wild-type c-Kit protein as well as with the mutant proteins
      YF702, YF728, and YF745. Ligand-induced association of p85 and PI 3-kinase
      activity were abolished with the YF719 c-Kit protein, and this was not due to
      different levels of expression of p85 or c-kit; and 3) c-kit receptor-bound p85
      was not phosphorylated on tyrosine residues. These results indicate that tyrosine
      719 within the 719YMDM motif in the kinase insert plays an important role in
      binding of p85 and that its phosphorylation is a prerequisite for binding of p85
      and the subsequent activation of PI 3-kinase.

PMID- 7509795
TI  - Identification of a human CD36 isoform produced by exon skipping. Conservation of
      exon organization and pre-mRNA splicing patterns with a CD36 gene family member,
      CLA-1.
AB  - During an examination of different cell types for CD36 mRNA splice variants, a
      partial cDNA from HEL cells was isolated and characterized. This CD36 cDNA had a
      309-base pair deletion following the region encoding the first putative
      transmembrane domain of CD36. The open reading frame of the deleted CD36 cDNA was
      retained and was predicted to yield a protein lacking 103 amino acid residues.
      The presence of this variant was confirmed in RNA pools from placental tissue by
      a reverse transcriptase-coupled polymerase chain reaction assay. Comparison of
      the HEL CD36 cDNA with the genomic sequence revealed that the mRNA represented by
      this variant CD36 cDNA was produced by a pre-mRNA splicing reaction that excluded
      exons 4 and 5. Transient expression of the variant CD36 cDNA in COS-1 cells
      showed that CD36 immunoreactive protein was expressed on the cell surface but
      lacked an antigenic epitope defined by amino acid residues 41-143. This cell
      surface glycoprotein (M(r) approximately 57,000) was of identical molecular
      weight as a CD36 isoform observed on the surface of HEL cells. The exclusion of
      exons during CD36 pre-mRNA processing appears to be conserved within one other
      CD36 gene family member, CLA-1.

PMID- 7509797
TI  - The role of individual exoribonucleases in processing at the 3' end of
      Escherichia coli tRNA precursors.
AB  - We have used an in vitro Escherichia coli tRNA processing system to investigate
      the specific role of individual exoribonucleases in the 3' maturation of tRNA
      precursors. The processing of pre-tRNA(Tyr)su3+ and pre-tRNA(2Arg) was studied
      using extracts from cells lacking one or multiple exoribonucleases or using
      purified RNases. Earlier genetic studies had suggested that multiple
      exoribonucleases contributed to the maturation of tRNA precursors, and this was
      proven directly in the studies described here. Complete 3' processing required
      the combined action of multiple exoribonucleases, and each RNase showed distinct
      specificities for maturation of the different parts of the 3' precursor segment.
      RNase II and polynucleotide phosphorylase were most effective in shortening long
      3' trailer sequences to intermediates with 2-4 extra 3' residues. Final trimming
      of the last few 3' nucleotides of these precursors was carried out most
      efficiently by RNases T and PH, but the two enzymes differed in their specificity
      for individual nucleotide positions. Depending on the tRNA precursor, the
      relative importance of the various RNases to the overall maturation process
      differed. We also showed that purified exoribonucleases can completely complement
      mutant extracts and that tRNA maturation can be totally reconstructed in vitro
      using purified enzymes. These studies provide the first detailed information
      about the specific role of individual exoribonucleases in tRNA processing, and
      bring us closer to defining a complete E. coli tRNA maturation pathway.

PMID- 7509798
TI  - Multiple guide RNAs for identical editing of Trypanosoma brucei apocytochrome b
      mRNA have an unusual minicircle location and are developmentally regulated.
AB  - We identified four different guide RNAs (gRNAs) that specify identical editing of
      Trypanosoma brucei apocytochrome b (CYb) mRNA, which indicates gRNA redundancy in
      T. brucei. All four gRNAs appear functional since they occur in chimeras, some of
      which contain an interesting gRNA 3' "extension." The gRNAs are encoded in
      different minicircles, rather than maxicircles as in other species. However,
      these gRNA genes are not between 18-base pair repeats as are the other minicircle
      gRNA genes in T. brucei. The three minicircles cloned contain the same gRNA
      genes, one of which is substantially diverged, all in the same order, indicating
      that they are related. CYb gRNA is less abundant in procyclic than bloodstream
      forms. Procyclic forms contain abundant edited CYb mRNA unlike bloodstream forms
      thus suggesting that CYb mRNA editing may be regulated at the level of gRNA
      utilization.

PMID- 7509799
TI  - A novel mechanism of colon carcinoma cell adhesion to the endothelium triggered
      by beta 1 integrin chain.
AB  - We have found a monoclonal antibody, called BV7, that rapidly stimulated by 6-10
      folds HT-29 colon carcinoma cell adhesion to resting human umbilical vein
      endothelial cells. This effect was directed to tumor cells and not to endothelial
      cells and was cell-specific. BV7 was also active on the HCCP-2998 but did not
      change adhesion to endothelial cells of other tumor cells (MG63 osteosarcoma,
      A375 melanoma, MHCC-1410 and Lovo colon carcinoma) even if, by flow cytometry,
      this monoclonal antibody could bind to them. Additionally, BV7 effect was
      substratum-specific, since it did not increase but rather blocked HT-29 adhesion
      to matrix proteins. Immunoprecipitation analysis and binding to specific
      transfectants revealed that BV7 recognizes beta 1-subunit of integrin receptors
      and antibody blocking experiments showed that alpha 2 beta 1 antibodies were able
      to counteract BV7 effect on HT-29 adhesion to endothelial cells. In contrast,
      antibodies directed to other integrins or endothelial adhesive receptors (E- and
      P-selectin, VCAM-1, ICAM-1, ICAM-2) were ineffective. Induction of HT-29 adhesion
      to endothelial cells by BV7 was Fc- and protein synthesis-independent but
      required metabolically active cells. The presence of physiological concentrations
      of divalent cations and of cytoskeletal integrity was not needed. Comparative
      studies with eight different prototypic beta 1 antibodies showed that five of
      them induced HT-29 adhesion to endothelial cells in a way unrelated to their
      ability to interfere with HT-29 adhesion to matrix proteins. Cross-blocking
      binding assays demonstrated that all the five antibodies recognized a
      topographically related epitope. Taken together these results provide evidence
      that beta 1 antibodies may trigger a novel pathway of HT-29 colon carcinoma
      adhesion to endothelial cells with different features in respect to other
      described mechanisms of tumor cell interaction with the endothelium.

PMID- 7509800
TI  - Kinetic and mutational analysis of human immunodeficiency virus type 1 reverse
      transcriptase inhibition by inophyllums, a novel class of non-nucleoside
      inhibitors.
AB  - Inophyllums are novel non-nucleoside inhibitors of human immunodeficiency virus
      (HIV) type 1 reverse transcriptase identified through an enzyme screening program
      and isolated from the plant Calophyllum inophyllum. The kinetics of reverse
      transcriptase inhibition by inophyllum B were characterized using recombinant
      purified enzyme, a heteropolymeric RNA template, and a scintillation proximity
      assay. Preincubation of inhibitor with the enzyme-template-primer complex for 11
      min was required for maximal inhibition of reverse transcriptase to occur,
      suggesting that inophyllum B had a slow on-rate and that template-primer must
      bind to reverse transcriptase prior to inhibitor binding. Inhibition of reverse
      transcriptase by inophyllums was shown to be reversible. When thymidine
      triphosphate was the variable substrate, inophyllum B inhibited reverse
      transcriptase noncompetitively with a Ki of 42 nM. Enzyme inhibition with respect
      to template-primer was uncompetitive with a Ki of 26 nM. Reverse transcriptase
      enzymes containing point mutations in which tyrosine 181 was changed to either
      cysteine or isoleucine exhibited marginal resistance to inophyllums but were
      resistant to (+)-(5S)-4,5,6,7-tetrahydro-9-chloro-5-methyl-6- (3-methyl-2
      butenyl)-imidazo[4,5,1-j,k][1,4]benzodiazepin-2-(1H)-t hione (TIBO R82913). A
      mutant enzyme in which tyrosine 188 was changed to leucine was cross-resistant to
      both inophyllum B and TIBO R82913, as was HIV type 2 reverse transcriptase. These
      studies suggest that inophyllum B and TIBO R82913 bind to distinct but
      overlapping sites. Inhibition of avian myeloblastosis virus reverse transcriptase
      and Moloney murine leukemia virus reverse transcriptase by inophyllum B was
      detectible, suggesting that these inhibitors may be more promiscuous than other
      previously described non-nucleoside inhibitors. Inophyllums were active against
      HIV type 1 in cell culture with IC50 values of approximately 1.5 microM. These
      studies imply that the inophyllums have a novel mechanism of interaction with
      reverse transcriptase and as such could conceivably play a role in combination
      therapy.

PMID- 7509801
TI  - Involvement of protein kinase C during activation of the mitogen-activated
      protein kinase cascade by leukemia inhibitory factor. Evidence for participation
      of multiple signaling pathways.
AB  - We show here that treatment of 3T3-L1 cells with leukemia inhibitory factor (LIF)
      stimulates the activation of mitogen-activated protein kinase kinase (MAPKK),
      mitogen-activated protein kinase (MAPK), and S6 protein kinase (S6K) activities
      both in a time- and dose-dependent manner. A single peak of MAPKK activity, four
      peaks of activity against the S6 synthetic peptide, RRLSSLRA (S6 peptide), and
      three distinct peaks toward myelin basic protein (MBP) were observed after Mono-Q
      chromatography of LIF-stimulated cell extracts. Two of the MBP kinase activities
      correlated with the stimulation of extracellular signal-regulated kinases 1 and
      2. Interestingly, down-regulation of protein kinase C (PKC) by chronic treatment
      of 3T3-L1 cells with phorbol ester was found to attenuate, but not block, the LIF
      mediated stimulation of MAPKK, MAPK, and S6K activities in 3T3-L1 cells.
      Treatment of 3T3-L1 cells with epidermal growth factor increased MAPKK, MAPK, and
      S6K activities to a similar extent as LIF, but this activation was not attenuated
      by down-regulation of PKC. Our results suggest that the full activation of the
      MAPK cascade by LIF may require inputs from multiple signaling pathways, one of
      which is dependent upon the presence of functional PKC.

PMID- 7509802
TI  - Agonist-selective regulation of polyphosphoinositide metabolism in pulmonary
      artery smooth muscle cells.
AB  - Using a rat pulmonary artery smooth muscle cell line (PAC1), detailed analysis of
      polyphosphoinositide (PPI) metabolism reveals receptor type-selective patterns in
      the formation of inositol phosphates and 3-hydroxyphosphorylated PPIs. Responses
      to several agonists that stimulate hypertrophy or proliferation were examined,
      and distinct categories of response profile were observed. Thrombin and
      angiotensin II stimulated the hydrolysis of phosphatidylinositol (PI) 4,5
      bisphosphate and the formation of several cytosolic species of inositol
      phosphates without the activation of PI 3-hydroxykinase. The response to thrombin
      was distinctive because a very large production of inositol 1,4-bisphosphate was
      accompanied by hydrolysis of PI 4-phosphate. The response to platelet-derived
      growth factor (PDGF) was distinguished by the production of the PI 3
      hydroxykinase product, PI 3,4,5-trisphosphate, and the appearance of PI 3
      hydroxykinase activity in immunoprecipitates. PDGF treatment of PAC1 cultures did
      not produce accumulation of detectable amounts of inositol 1,4,5-trisphosphate,
      although a small sustained elevation in the level of inositol monophosphate and a
      gradual accumulation of inositol 1,3,4-trisphosphate were observed.
      Characterization of these distinctive responses permitted us to correlate agonist
      regulated PPI metabolism with induction of immediate-early genes and stimulation
      of hypertrophy or proliferation of PAC1 cultures (Rothman, A., Wolner, B.,
      Button, D., and Taylor, P. (1994) J. Biol. Chem. 269, 6399-6404). Thrombin
      stimulated PPI turnover and the production of a high level of inositol
      bisphosphate may be early signals linked to the induction of fosB and PAC1 cell
      hypertrophy, whereas the activation of PI 3-hydroxykinase and the accumulation of
      PI 3,4,5-trisphosphate in response to PDGF appear to be associated with
      mitogenesis.

PMID- 7509803
TI  - Studies on the glycoprotein associated with Rh (rhesus) blood group antigen
      expression in the human red blood cell membrane.
AB  - The blood group Rh antigens are associated with non-glycosylated 30-kDa
      erythrocyte membrane proteins (the Rh30 polypeptides) and the Rh glycoprotein. We
      used antipeptide antibodies to study the Rh glycoprotein in human erythrocyte
      membranes. The Rh glycoprotein was present in Rhnull U+ve cells. However, the N
      glycan chain of the Rh glycoprotein in Rhnull U+ve cells was smaller than in
      normal cells. In contrast, the N-glycan chain of the Rh glycoprotein was larger
      than normal in glycophorin B-deficient red cells. We suggest that this
      observation reflects a lower rate of movement of newly synthesized Rh
      glycoprotein through intracellular membranes to the cell surface in the absence
      of glycophorin B, and that in normal red cells glycophorin B facilitates the
      movement of the Rh protein complex to the cell surface. Our results provide
      evidence for the intracellular interaction of at least three proteins, the Rh
      glycoprotein, Rh30 polypeptides, and glycophorin B during the biosynthesis and
      cell surface expression of the Rh complex. These observations are likely to be
      important for the successful design of expression systems for the blood group Rh
      antigens.

PMID- 7509804
TI  - 1,25-dihydroxyvitamin D3 dissociates production of interstitial collagenase and
      92-kDa gelatinase in human mononuclear phagocytes.
AB  - To study the effect of mononuclear cell differentiation on metalloproteinase
      production, the human monocytic cell lines U937 and THP-1 were exposed to two
      well known differentiating agents, the phorbol esters (phorbol myristate acetate
      (PMA)) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). With U937 cells, PMA-induced
      differentiation increased the production of both interstitial collagenase and 92
      kDa gelatinase, whereas exposure to 1,25-(OH)2D3 induced full interstitial
      collagenase expression in the absence of any detectable 92-kDa gelatinase
      production. In fact, when U937 cells were differentiated with PMA and then
      exposed to vitamin D3, the hormone actually suppressed phorbol-induced 92-kDa
      gelatinase biosynthesis. With THP-1 cells, PMA also induced the production of 92
      kDa gelatinase fully, but unlike U937 cells, the combination of PMA and 1,25
      (OH)2D3 was required for substantial interstitial collagenase biosynthesis. As
      with U937 cells, the addition of 1,25-(OH)2D3 to PMA-differentiated THP-1 cells
      caused a dose-dependent inhibition of 92-kDa gelatinase production. Northern
      hybridizations demonstrated that both phorbol esters and vitamin D3 act on
      monocytic cell lines at a pretranslational level. To determine whether
      metalloproteinase biosynthesis in normal differentiated mononuclear phagocytes
      was also modified by 1,25-(OH)2D3, human blood monocytes and alveolar macrophages
      were exposed to this hormone. In both cell types, basal and Staphylococcal
      stimulated 92-kDa gelatinase production was markedly inhibited by 1,25-(OH)2D3.
      In contrast, interstitial collagenase production was completely unaffected by the
      hormone. In summary, the two major metalloproteinases produced by monocytic cells
      are regulated via distinct molecular pathways by the action of PMA and 1,25
      (OH)2D3. Furthermore, vitamin D3 completely dissociates the production of 92-kDa
      gelatinase and interstitial collagenase in human mononuclear phagocytes.

PMID- 7509806
TI  - Human serum biotinidase. cDNA cloning, sequence, and characterization.
AB  - Biotinidase (EC 3.5.1.12) catalyzes the hydrolysis of biocytin, the product of
      biotin-dependent carboxylase degradation, to biotin and lysine. Biotinidase
      deficiency is an inherited metabolic disorder of biotin recycling that is
      characterized by neurological and cutaneous abnormalities, and can be
      successfully treated with biotin supplementation. Sequences of tryptic peptides
      of the purified human serum enzyme were used to design oligonucleotide primers
      for polymerase chain reaction amplification from human hepatic total RNA to
      generate putative biotinidase cDNA fragments. Sequence analysis of a cDNA
      isolated from a human liver library by plaque hybridization with the largest cDNA
      probe revealed an open reading frame of 1629 bases encoding a protein of 543
      amino acid residues, including 41 amino acids of a potential signal peptide.
      Comparison of the open reading frame with the known biotinidase tryptic peptides
      and recognition of the expressed protein encoded by this cDNA by monoclonal
      antibodies prepared against purified biotinidase demonstrated the identity of
      this cDNA. Southern analyses suggested that biotinidase is a single copy gene and
      revealed that human cDNA probes hybridized to genomic DNA from mammals, but not
      from chicken or yeast. Northern analysis indicated the presence of biotinidase
      mRNA in human heart, brain, placenta, liver, lung, skeletal muscle, kidney, and
      pancreas.

PMID- 7509805
TI  - Different patterns of calcium signaling triggered through two components of the B
      lymphocyte antigen receptor.
AB  - The engagement of the B cell antigen receptor is the first step of antigenic
      stimulation of B lymphocytes. This step is followed by a series of biochemical
      events, including the activation of protein-tyrosine kinases, phosphoinositide
      turnover, and multiple patterns of calcium mobilization, which lead to the
      regulation of gene transcription and cellular responses. The B cell antigen
      receptor complex is composed of membrane immunoglobulins (as antigen recognition
      subunits) and associated chains (Ig-alpha and Ig-beta) that couple the receptor
      to cytoplasmic protein kinases. To investigate independently the relative
      signaling capacity of Ig-alpha and Ig-beta, chimeric proteins containing their
      cytoplasmic domains were expressed in a B cell line. We found that Ig-alpha and
      Ig-beta activate two distinct intracellular signaling pathways. The engagement of
      Ig-alpha chimeras induces a complete release of calcium from intracellular
      stores, followed by transmembrane calcium influx and late cell activation
      signals, detected by lymphokine secretion. In contrast, Ig-beta chimeras do not
      induce lymphokine secretion or calcium influx, but induce short oscillatory
      release of calcium, dependent on the activity of the Ca-ATPase pump of the
      endoplasmic reticulum. These results provide a structural basis for the diversity
      of B cell responses.

PMID- 7509807
TI  - Characterization of the interaction of N-acyl-L-tryptophan benzyl ester
      neurokinin antagonists with the human neurokinin-1 receptor.
AB  - We have recently shown that a series of N-acyl-L-tryptophan benzyl esters are
      potent substance P antagonists (Macleod, A. M., Merchant, K. J., Cascieri, M. A.,
      Sadowski, S., Ber, E., Swain, C. J., and Baker, R. (1993) J. Med Chem. 14, 2044
      2045). We now report the detailed characterization of the interaction of N-acetyl
      L-tryptophan-3,5-bistrifluoromethyl benzyl ester (L-732,138) with the human
      neurokinin-1 (NK-1) receptor. L-732,138 inhibits the binding of 125I-substance P
      to the cloned human NK1 receptor expressed in Chinese hamster ovary cells with an
      IC50 of 2.3 +/- 0.7 nM. In contrast, it has 200-fold lower affinity for the
      cloned rat NK-1 receptor and has > 1000-fold lower affinity for the human NK-2
      and NK-3 receptors. L-732,138 acts as a competitive antagonist of substance P, as
      shown by functional Schild analysis of the inhibition of substance P-induced
      inositol phosphate synthesis, by kinetic analysis of the dissociation rate, and
      by thermodynamic analysis of the equilibrium binding of 125I-substance P to the
      NK-1 receptor. L-732,138 also competitively inhibits the binding of the
      quinuclidine amine antagonist, [125I]L-703,606, to the receptor. The compound has
      230- and 10-fold reduced affinity for mutant NK-1 receptors in which histidine
      265 or histidine 197, respectively, are replaced with alanine. We have previously
      shown that these residues play key roles in the binding of quinuclidine
      antagonists to the NK-1 receptor. These results suggest that the tryptophan and
      quinuclidine series of NK-1 antagonists bind to similar binding sites on the
      human NK-1 receptor.

PMID- 7509808
TI  - Cloning of a Na/Pi cotransporter from opossum kidney cells.
AB  - Opossum kidney (OK) cells have been extensively used to study cellular mechanisms
      of renal proximal tubular Na/P(i) cotransport. We have cloned a cDNA (NaPi-4)
      most likely encoding an apical Na/P(i) cotransporter from OK cells. The cloning
      strategy was based on homology to the recently cloned human renal (NaPi-3)
      Na/P(i) cotransporter (Magagnin, S., Werner, A., Markovich, D., Sorribas, V.,
      Stange, G., Biber, J., and Murer, H. (1993) Proc. Natl. Acad. Sci. U. S. A. 90,
      5979-5983). Kinetic characterization (P(i) interaction, sodium interaction, and
      pH dependence) of NaPi-4-induced Na/P(i) uptake showed high similarity to apical
      Pi transport in OK cell monolayers. The NaPi-4 cDNA is 2548 base pairs long and
      encodes a protein of 70.5 kDa, containing at least 8 predicted transmembrane
      domains. Northern blot analysis with OK cell mRNA shows a NaPi-4-related signal
      (2.5 kilobases) in cells grown on impermeant and permeant supports. Hybrid
      depletion with NaPi-4 antisense oligonucleotides abolished the mRNA-induced
      Na/P(i) cotransport in oocytes. Similarly, NaPi-4 antisense oligonucleotides
      inhibited (up to 70%) Na/P(i) cotransport in OK cell monolayers. We presume that
      NaPi-4 is closely related to the OK cell apical Na/P(i) cotransporter.

PMID- 7509809
TI  - The residues Leu(Ile)475-Ile(Leu, Val, Ala)476, contained in the extended
      carboxyl cytoplasmic tail, are critical for targeting of the resident lysosomal
      membrane protein LIMP II to lysosomes.
AB  - LIMP II, a type II lysosomal integral membrane protein, and the CD36/LIMP II
      construct are targeted to lysosomes by means of a signal expressed in the
      tyrosine-lacking carboxyl cytoplasmic tail of LIMP II (Vega, M. A., Rodriguez,
      F., Segui, B., Cales, C., Alcalde, J., and Sandoval, I. V. (1991) J. Biol. Chem.
      266, 16269-16272; Vega, M. A., Segui-Real, B., Garcia, J. A., Cales, C.,
      Rodriguez, F., Vandekerckhove, J., and Sandoval, I. V. (1991) J. Biol. Chem. 266,
      16818-16824). Substitution of Leu475 with Ile resulted in a decreased efficiency
      of targeting. Mutant forms produced by substituting Leu475 by hydrophobic
      residues with either large (Val) or small (Ala, Gly) side chains, or by a charged
      residue (Asp), showed inhibited targeting. In contrast, the contiguous Ile476
      residue could be replaced by either Leu, without loss in the efficiency of
      targeting, or by Val or Ala, with some impediment. Substitution of Ile476 by
      either Gly or Asp inhibited completely the targeting. The addition of the
      sequence Ser-Trp-Asp to the carboxyl end of the construct did not interfere with
      targeting. Data from 1H NMR analysis of the icosapeptide corresponding to the
      carboxyl cytoplasmic tail of LIMP II indicated the predominance of structures
      with extended random coil conformations, suggesting that the targeting signal is
      contained in a domain with an extended configuration.

PMID- 7509810
TI  - Molecular cloning, structure, and chromosomal localization of the human inducible
      nitric oxide synthase gene.
AB  - Nitric oxide, a multifunctional effector molecule synthesized by nitric oxide
      synthase (NOS) from L-arginine, conveys signals for vasorelaxation,
      neurotransmission, and cytotoxicity. Three different NOS isoforms have been
      identified which fall into two distinct types, constitutive and inducible. The
      inducible NOS (iNOS) isoform is expressed in a variety of cell types and tissues
      in response to inflammatory agents and cytokines. The human iNOS (NOS2) gene was
      isolated on overlapping cosmid clones from a human genomic library using both the
      murine macrophage and the human hepatocyte iNOS cDNAs as probes. All isolated
      cosmids were part of a single genomic locus and no other genomic loci were
      identified or isolated. Analysis of this locus indicated that the human iNOS gene
      is approximately 37 kilobases in length and consists of 26 exons and 25 introns.
      Primer extension analysis of lipopolysaccharide and cytokine-stimulated human
      hepatocyte RNA mapped the transcriptional initiation site 30 base pairs
      downstream of a TATA sequence, and a 400-base pair 5'-flanking region was found
      to be structurally similar to the recently described murine iNOS promoter.
      Polymerase chain reaction analysis of a human/rodent genomic DNA somatic cell
      hybrid panel and fluorescent in situ hybridization indicated that the human iNOS
      gene is located on chromosome 17 at position 17cen-q11.2.

PMID- 7509811
TI  - Identification of a TPA-responsive element mediating preferential transactivation
      of the galanin gene promoter in chromaffin cells.
AB  - The gene encoding the neuropeptide galanin is upregulated by second messenger
      signal transduction pathways in bovine chromaffin cells. To identify its
      transcriptional regulatory elements, 5'-flanking sequences of the galanin gene
      were transiently transfected into primary cultures of bovine chromaffin cells
      within reporter gene constructs. Multiple regions of the galanin 5' flank seem to
      be necessary for basal activity. The most promoter-proximal of these regions
      contains a sequence (TGACG) -66 to -62 nucleotides upstream from the
      transcriptional start site which mediates stimulation by 12-O
      tetradecanoylphorbol-13-acetate (TPA), as demonstrated by site-directed
      mutagenesis and cis-activation experiments. This cis-regulatory element mediates
      preferential TPA stimulation of transcription from the galanin promoter in
      chromaffin cells compared with bovine endothelial or HeLa cells. DNA-protein
      binding assays indicate that an oligonucleotide that includes the galanin TPA
      responsive element (GTRE) binds specifically to proteins from nuclear extracts of
      chromaffin cells. TPA treatment persistently increases this binding activity in
      chromaffin but not in endothelial cells. Mutation of the galanin promoter within
      the -66 to -62 region renders it unresponsive to transcriptional stimulation by
      TPA, and a correspondingly mutated oligonucleotide fails to bind chromaffin cell
      nuclear proteins in a gel-shift assay. Chromaffin cell nuclear extracts also
      contain proteins that bind consensus TPA-responsive (TRE) and cyclic AMP
      responsive (CRE) elements. GTRE, TRE, and CRE oligonucleotides all compete more
      efficiently for protein binding to their labeled congeners than for protein
      binding to either of the other labeled oligonucleotides, suggesting that the
      GTRE, TRE, and CRE oligonucleotides, suggesting that the GTRE, TRE, and CRE
      oligonucleotides each bind unique as well as common proteins, likely to be
      members of the Jun/Fos and cAMP-responsive element-binding protein/activating
      transcription factors (CREB/ATF) families of transcription factors, in chromaffin
      cells.

PMID- 7509812
TI  - CD20 monoclonal antibodies stimulate extracellular cleavage of the low affinity
      receptor for IgE (Fc epsilon RII/CD23) in Epstein-Barr-transformed B cells.
AB  - This study demonstrates that monoclonal antibodies to the B cell-specific CD20
      molecule down-regulate both constitutive and interleukin-4-induced CD23
      expression on Epstein-Barr-transformed B cells. This effect of CD20 antibody B1
      does not take place at the transcriptional level as shown by the lack of effect
      on the CD23 mRNA level. Incorporation of 35S-labeled amino acids into CD23
      polypeptide chain is not affected either. In cycloheximide-treated cells, B1
      increases the decline of CD23 from the cell surface. The disappearance of CD23
      molecule correlates with an increase of soluble CD23 fragments detected in the
      culture medium. Taken collectively, these results indicate that CD20 mAb B1
      stimulates the cleavage of the CD23 molecule at the surface of B cells.

PMID- 7509813
TI  - Rabbit interleukin-1 receptor antagonist. Cloning, expression, functional
      characterization, and regulation during intestinal inflammation.
AB  - Genomic and cDNA clones for rabbit interleukin-1 receptor antagonist (IL-1ra)
      were isolate based on homology with the human, mouse, and rat IL-1ra gene. A
      partial genomic clone, obtained by screening a rabbit genomic library, contained
      coding sequences for the carboxyl-terminal 108 amino acids of rabbit IL-1ra. Two
      classes of cDNA for rabbit IL-1ra were obtained using RNA from inflamed rabbit
      colon tissue. One class of cDNA coded for a secreted form of IL-1ra, whereas the
      other coded for a putative intracellular form of rabbit IL-1ra. The latter form
      is similar to that isolated from human epithelial cells. A partially synthetic
      rabbit IL-1ra gene was constructed and expressed in Escherichia coli. The
      recombinant rabbit IL-1ra was purified to homogeneity by ion exchange
      chromatography. Its affinity was similar to that of human IL-1ra for the human
      and mouse type I IL-1 receptor. From the cDNA clone and the purified recombinant
      protein, specific probes were developed for measuring levels of rabbit IL-1ra
      mRNA and protein in normal and inflamed rabbit tissues. Unlike IL-1 alpha and IL
      1 beta, IL-1RA mRNA and protein were present at detectable levels in normal
      rabbit colon. During the development of an experimental formalin-immune complex
      colitis, rabbit IL-1 alpha showed a dramatic increase in tissue levels,
      consistent with previous results; IL-1ra also increased 3-4-fold. Treatment of
      colitis rabbits with corticosteroids significantly suppressed neutrophil
      infiltration, corticosteroid treatment suppressed IL-1ra but not IL-1 alpha mRNA
      steady-state levels. Our observations demonstrate that IL-1 and IL-1ra synthesis
      is differentially regulated in healthy and inflamed intestinal tissue.

PMID- 7509814
TI  - Characterization of a new monoclonal antibody to triplex DNA and
      immunofluorescent staining of mammalian chromosomes.
AB  - A monoclonal antibody, Jel 466, was prepared from mice immunized with
      poly[d(Tm5C)].poly[d(GA)]. The binding of Jel 466 to nucleic acids was
      characterized by solid phase radioimmunoassays and competition experiments. There
      was no binding to single-stranded DNAs or to duplexes which could not form
      triplexes. In addition, the antibody preferred the triplex form of
      poly[d(TC)].poly[d(GA)]; it bound weakly to the triplex derived from
      poly[d(G)].poly[d(C)], but there was no interaction with
      poly[d(T)].poly[d(A)].poly[d(T)]. This pattern of specificity is very different
      from that of Jel 318, a triplex-specific antibody that will bind to
      poly[d(T)].poly[d(A)].poly[d(T)]. The amino acid sequence of Jel 466 also showed
      very little homology with Jel 318, although both contain many positively charged
      amino acids. The immunofluorescent staining of mouse and human chromosomes with
      Jel 466 was studied. In all cases, there was a marked reciprocal relationship
      between the pattern of Jel 466 on the one hand and that of Hoechst 33258 and Jel
      318 on the other. Jel 466 was negative for C-band and G-band but positive for R
      band, whereas the opposite was found for Hoechst and Jel 318. Since C and G-bands
      are AT-rich and R-bands are GC-rich, these staining patterns match the sequence
      preferences of the two antibodies. Thus the base composition of triplex-forming
      DNA differs from domain to domain.

PMID- 7509816
TI  - Suppressive effect of FK-506, a novel immunosuppressant, against MPTP-induced
      dopamine depletion in the striatum of young C57BL/6 mice.
AB  - Systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is
      known to damage the dopaminergic nigrostriatal system in C57BL/6 mice. We have
      investigated the effects of immunosuppressants, FK-506 and cyclosporin A (CsA),
      on MPTP-induced dopamine (DA) depletion in the striatum of young C57BL/6 mice. 10
      days after MPTP treatment (25 mg/kg i.p. given daily, 5 days), DA in the striatum
      was depleted by 80%. However, pretreatment with FK-506, a novel
      immunosuppressant, significantly protected MPTP-induced DA depletion in the
      striatum, but FK-506 itself did not affect the DA content. CsA, another
      immunosuppressant, also protected MPTP-induced DA depletion. From these results
      can be seen that immunosuppressants seem to inhibit MPTP neurotoxicity toward
      nigrostriatal dopaminergic neurons of young C57BL/6 mice.

PMID- 7509817
TI  - Influence of pulsationless milking on teat canal keratin and mastitis.
AB  - Twenty-four Holstein cows, producing at least 21 kg of milk/d, were used in two
      replicate experiments to determine the effect of presence or absence of pulsation
      on loss of teat canal keratin during machine milking. Left quarters were milked
      without pulsation and right quarters were milked with pulsation. On d 0 and 10,
      keratin was collected from one left and from one right teat canal of each cow
      prior to milking and from the remaining two teat canals after milking. Milk was
      collected for assessment of SCC and bacteriological status on d 0 and
      approximately every 3 d until d 18. Quantity of keratin recovered before milking
      on d 10 did not differ between teats milked with or without pulsation, but loss
      of keratin because of milking was greater from teats milked with pulsation. By d
      7, 30% (12 of 43) of quarters milked without pulsation had become infected, but
      no (0 of 47) quarters milked with pulsation were infected. By d 14 to 16, new
      infections had increased to 68% (28 of 41) of quarters milked without pulsation
      and 2% (1 of 43) in quarters milked with pulsation; mean SCC in pulsationless
      quarters increased sevenfold relative to pulsation quarters. Protein and water
      content of keratin did not differ because of treatment, and changes in lipid
      composition were minor. Histological analysis of the teats of 4 cows indicated
      that the mean diameter of the teat canal, within 2 h after milking, was greater
      without pulsation than with pulsation (680 vs. 483 microns).

PMID- 7509818
TI  - Progressive alterations of cytokeratin expressions in the process of chronic
      arsenism.
AB  - Recent studies of an endemic occurrence of chronic arsenism in a limited area on
      the southwest coast of Taiwan are focusing on its cytokeratin analysis in hopes
      of tracing the disease's biochemical expression. Specimens were obtained from
      uninvolved skin and arsenical cancers including Bowen's disease, basal cell
      carcinoma, and squamous cell carcinoma. In this study, we used two-dimensional
      polyacrylamide gel electrophoresis to analyse cytokeratin expression. Progressive
      alterations in cytokeratin expression were found in various skin lesions. These
      include an expression of K16 in the uninvolved skin; K16 and K6 in Bowen's
      disease; and K16, K6 and K17 in squamous cell carcinoma and basal cell carcinoma.
      In addition, we found that the K1 isoelectric variants shifted to more acidic
      forms with the complete absence of K1 in basal cell carcinoma. K16 expression in
      uninvolved skin indicates that it is nevertheless in a hyperproliferative status.
      K17 was expressed in squamous cell carcinoma and basal cell carcinoma, but not in
      Bowen's disease. The progressive impairment of phosphorylation of K1 and K2 in
      the process of chronic arsenism provides us with a suitable model for studying
      the biological significance of phosphorylation in intermediate filaments during
      chemical carcinogenesis.

PMID- 7509819
TI  - Occupational sensitization to Plasmopara viticola.
AB  - Molds of the class of Oomycetes are of allergologic importance in special cases.
      However, probes are not commercially available for diagnostic purposes. Our case
      report is based on the medical history of a greenhouse worker who had atopic
      syndrome. He handled pure cultures of defined fungi and plants. A sensitization
      to pseudo mildew growing on grapevine (Plasmopara viticola) was found. Skin prick
      test and histamine release test results were positive when extract of P. viticola
      was used. Detection of IgE reactivities against pseudo mildew via binding tests,
      Western blot analysis, and isoelectric focusing immunoblot confirmed the
      diagnosis. To our knowledge these results demonstrate for the second time a
      sensitization to Oomycetes.

PMID- 7509815
TI  - Nuclear export of different classes of RNA is mediated by specific factors.
AB  - Various classes of RNA are exported from the nucleus to the cytoplasm, including
      transcripts of RNA polymerase I (large ribosomal RNAs), II (U-rich small nuclear
      RNAs [U snRNAs], mRNAs), and III (tRNAs, 5S RNA). Here, evidence is presented
      that some steps in the export of various classes of nuclear RNA are mediated by
      specific rather than common factors. Using microinjection into Xenopus oocytes,
      it is shown that a tRNA, a U snRNA, and an mRNA competitively inhibit their own
      export at concentrations at which they have no effect on the export of
      heterologous RNAs. While the export of both U snRNAs and mRNAs is enhanced by
      their 7-methyl guanosine cap structures, factors recognizing this structure are
      found to be limiting in concentration only in the case of U snRNAs. In addition
      to the specific factors, evidence for steps in the export process that may be
      common to at least some classes of RNA are provided by experiments in which
      synthetic homopolymeric RNAs are used as inhibitors.

PMID- 7509820
TI  - Inhibition of IgE- and non-IgE-mediated histamine release from human basophil
      leukocytes in vitro by a histamine H1-antagonist, desethoxycarbonyl-loratadine.
AB  - Loratadine, a new nonsedating histamine H1-antagonist, has been shown to inhibit
      immunologic release of inflammatory mediators in addition to its H1-receptor
      blocking properties. After oral administration, the agent is metabolized
      primarily to desethoxycarbonyl-loratadine (DCL). The basic piperidine, DCL, is
      readily soluble in water, whereas the nonbasic urethane, loratadine, is
      insufficiently soluble in water for some in vitro investigations. Therefore we
      used the metabolite, DCL, to study its influence on in vitro leukocyte histamine
      release (LHR) in 24 allergic and 22 nonallergic subjects. IgE-mediated and
      calcium ionophore A23187-induced LHR were inhibited by DCL in a dose-dependent
      fashion (values of drug concentration to induce 30% inhibition after stimulation
      with inhalant antigen, anti-IgE, concanavalin A, and calcium ionophore A23187
      were 6, 8, 5, and 11 mumol/L, respectively). Higher concentrations of DCL caused
      mediator release in all subjects (n = 45, 30 mumol/L DC: 11% +/- 2% LHR, 100
      mumol/L DCL: 35% +/- 1% LHR), abolishing any inhibitory effect of the drug. Rapid
      onset of inhibition by 10 mumol/L DCL was found in kinetic studies (n = 10). The
      inhibition of anti-IgE-induced histamine secretion was synergistically increased
      by simultaneous preincubation of DCL with the potent histamine H2-agonist, FRA
      19. Additional data indicate that the inhibition of LHR by DCL might involve
      biochemical events that occur after cellular Ca++ influx because LHR induced by N
      formyl-methionyl-leucyl-phenylalanine or the phorbol ester, 12-O-tetradecanoyl
      phorbol-12-acetate, was not significantly affected by DCL.

PMID- 7509821
TI  - Tumor necrosis factor-alpha release during systemic reaction in cold urticaria.
AB  - Primary cold urticaria (PCU) characterized by the association of urticaria,
      angioedema, and sometimes a shock-like reaction after cold exposure, is usually
      considered to be linked with histamine and prostaglandin D2 release by mast
      cells. To determine the involvement of cytokines, we studied the release of tumor
      necrosis factor-alpha (TNF-alpha) in the blood of the efferent vein after
      immersion of the hand in chilled water. Five patients with PCU were compared with
      a control population (three patients with nonphysical urticaria and three healthy
      subjects). Among patients with PCU who underwent the cold immersion test, two
      exhibited a shock-like reaction with a large urticarial plaque (patients 1 and
      2), one had only a mild cutaneous reaction, and two had no reaction. Patient 1
      was reevaluated after 6 months of treatment with H1 and H2 antihistamines: he did
      not respond to this challenge. All controls were strictly negative. Histamine was
      released within the first minute after the challenge in the three patients with
      PCU, but at a higher level for the two patients who had a systemic reaction. TNF
      alpha was undetectable in the blood of the patient with only a mild cutaneous
      reaction, whereas TNF-alpha release was observed for the two patients with a
      systemic reaction, 2 and 6 minutes after the end of the cold immersion test. The
      two other patients and the control subjects released neither histamine nor TNF
      alpha. In parallel, pathologic and immunohistochemical (with a rabbit anti-TNF
      alpha antibody) studies were performed on skin biopsy specimens collected 10
      minutes after ice-cube test.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509822
TI  - Origins of nerve terminals containing nitric oxide synthase in the guinea-pig
      coeliac ganglion.
AB  - Nitric oxide synthase was localised immunohistochemically and by NADPH diaphorase
      activity in two groups of nerve terminals and in rare cell bodies in the guinea
      pig coeliac ganglion. Strongly reactive varicose terminals surrounded a subgroup
      of principal ganglion cells, most of which were in the medial lobes of the
      ganglion and most of which were somatostatin immunoreactive. A second set of
      varicose terminals, which were less intensely reactive, were found throughout the
      ganglia. Nitric oxide synthase containing nerve cell bodies in the
      intermediolateral cell columns of the spinal cord were labelled by dye
      retrogradely transported from the coeliac ganglion. Lesion of nerve connections
      between abdominal viscera and the coeliac ganglion caused a loss of the strongly
      reactive fibres, while the widely distributed, less intensely reactive fibres
      persisted. It is concluded that nitric oxide synthase terminals in the coeliac
      ganglion come from two sources, sympathetic preganglionic neurons and
      intestinofugal neurons.

PMID- 7509823
TI  - Neurodegeneration in sweat glands and skin of aged rats.
AB  - In order to compare age-associated neurodegenerative changes in peripheral nerves
      of laboratory mammals and humans, we have investigated the density and pattern of
      different nerve populations innervating sweat glands of ageing rats and compared
      our results with a previous study of the innervation of human sweat glands. We
      have also studied age-changes in subepidermal afferent nerves that may be
      involved in reflex activation of sweat glands. Total nerve density, measured by
      immunohistochemical staining for the general neuronal marker, protein gene
      product (PGP9.5) and image analysis, showed a significant decline around
      secretory coils of sweat glands of old compared to young rats. Marked reductions
      of acetylcholinesterase (AChE) histochemical staining and of vasoactive
      intestinal polypeptide (VIP)- and calcitonin gene-related peptide (CGRP)-like
      immunoreactivity were observed in nerves around sweat glands. In the sub
      epidermis, PGP- and CGRP-like immunoreactive nerves were significantly reduced in
      old rats. The age-related changes in sweat gland innervation of old rats were
      comparable to those reported in elderly human subjects suggesting that these
      tissues may provide a suitable model for experimental studies of neuronal ageing.

PMID- 7509825
TI  - CD40 preferentially costimulates activation of CD4+ T lymphocytes.
AB  - CD40 is a membrane differentiation antigen constitutively expressed on B cells
      that induces B cell growth and Ig synthesis after ligation with anti-CD40 mAb or
      with the recently identified CD40 ligand (CD40L). CD40L is rapidly induced on T
      cells after activation with anti-CD3 mAb or mitogens. While CD40-CD40L
      interactions are clearly beneficial to B cells, we speculated that a reciprocal
      costimulation of T cells might also occur. We have used genetic transfection to
      demonstrate that interactions between human small, resting T cells and CD40+
      murine transfectants substantially augmented anti-CD3 induced T cell
      proliferation and resulted in the generation of CTL. T cell proliferation
      costimulated by CD40 was IL-2 dependent. The ability of CD40+ transfectants to
      costimulate T cell proliferation was specific in that VCAM-1+, CD54+, CD72+,
      CD56+, CD31+, and fas+ transfectants in the same host cells were inactive. CD4+ T
      cells preferentially responded to CD40 costimulation, whereas CD8+ T cells were
      substantially less reactive. By contrast, costimulation with B7 transfectants
      induced equivalent proliferation in the CD4+ and CD8+ T cell subsets. In
      addition, adult naive and memory T cells, as well as cord blood T cells, were
      responsive to CD40. These findings suggest that the CD40-CD40L costimulation
      pathway may allow for selective expansion of CD4+ T cells after interaction with
      CD40-bearing APC. The relatively restricted expression of CD40 on APC, as well as
      on medullary and cortical thymic epithelium, indicates a possible role for this
      interaction in T cell differentiation and activation.

PMID- 7509824
TI  - Projections of nitric oxide synthase- and peptide-containing neurons in the small
      and large intestines of the toad (Bufo marinus).
AB  - The projections of galanin (GAL)- and vasoactive intestinal peptide (VIP)
      immunoreactive (IR) and nitric oxide synthase (NOS)-containing neurons in the
      small and large intestines of the amphibian Bufo marinus were investigated by
      their reactions to surgical interruption (myotomy). In the small intestine,
      myotomy caused accumulation of GAL- and VIP-IR and of NADPH diaphorase reaction
      product (revealing NOS) in cut axons on the oral side of the operation site. On
      the anal side there was loss of GAL-IR axons from the circular muscle and
      myenteric plexus and long, anally directed processes could be traced from GAL-IR
      nerve cell bodies. There was no significant loss of VIP-IR or NADPH diaphorase
      from nerve fibres in the myenteric plexus or circular muscle layer, although
      anally-directed axons could be traced from nerve cell bodies on the anal side of
      the operation sites. In the large intestine, myotomy caused accumulation of VIP
      IR and of NADPH diaphorase reaction product in cut axons on the oral side of the
      operation site. Anal to the cut, although there was no significant loss of these
      fibres from the muscle or myenteric plexus, anally directed axons could be traced
      from nerve cell bodies. GAL-IR fibres in the large intestine are of two types: a
      few contain GAL-IR alone and are thought to arise from enteric neurons; many
      contain both GAL- and SOM-IR and are thought to arise from nerve cell bodies in
      the hindgut. Myotomy caused an accumulation of GAL/SOM-IR material in fibres on
      the anal side of the cut and a substantial decrease in the number of fibres on
      the oral side. There was no detectable effect of myotomy on the GAL-IR fibres,
      although an abnormally high density of GAL-IR nerve cell bodies was found oral to
      the cut. These results indicate that VIP-IR and NOS-containing enteric neurons
      project in an oral to anal direction in the toad small and large intestines. Some
      of the neurons have short anal projections to the circular muscle. GAL-IR enteric
      neurons have similar projections in the small intestine, but their projections
      could not be determined in the large intestine. GAL/SOM-IR axons in the large
      intestine project from anal to oral. Myotomy in the large intestine appears to
      induce an increased or de novo expression of GAL-IR in enteric neurons oral to
      the cut.

PMID- 7509826
TI  - Adjuvant-free in vivo targeting. Antigen delivery by alpha 2-macroglobulin
      enhances antibody formation.
AB  - The proteinase "inhibitor" alpha 2-macroglobulin (alpha 2M) is able to entrap and
      form covalent linkages with diverse proteins during a transient proteinase
      activated state. These complexes are rapidly endocytosed after binding to
      receptors present on macrophages and other cells. We have previously shown that
      compared to free hen egg lysozyme (HEL), alpha 2M-complexed HEL undergoes
      enhanced macrophage uptake, processing, and presentation to T hybridoma clones in
      vitro. Inasmuch as it is not clear whether T hybridoma responses accurately
      reflect primary immune responses in vivo, we studied antibody production in
      rabbits using two Ag complexed with either human alpha 2M (H alpha 2M) or a
      homologous protein purified from rabbit plasma, alpha 1-macroglobulin (R alpha
      1M). Pathogen-free NZW rabbits received s.c. injections with adjuvant-free
      preparations of free HEL or porcine pancreatic elastase (PPE), H alpha 2M-HEL-PPE
      complexes, R alpha 1M-HEL-PPE complexes, or mixtures of the uncomplexed proteins.
      Complexing the Ag to alpha 2M resulted in 10 to 500-fold higher IgG titers
      compared to uncomplexed controls. Injection of Ag complexed to either H alpha 2M
      or R alpha 1M resulted in levels of anti-HEL IgG comparable to those elicited by
      emulsification in CFA. Inasmuch as inflammatory proteinases such as neutrophil
      elastase can initiate covalent complex formation with alpha 2M, we propose that
      "proteinase-activated" alpha 2M may mediate receptor-enhanced Ag uptake by
      macrophages, resulting in augmented Ag processing and antibody production.

PMID- 7509827
TI  - Activated CD4+ T cells induce CD40-dependent proliferation of human B cell
      precursors.
AB  - Anti-CD3-activated human CD4+ T cell clones were found to induce proliferation of
      CD10+, CD19+, surface(s) Ig- B cell precursors (BCP) isolated from human fetal
      bone marrow. The great majority of the B lineage cells recovered in cocultures of
      BCP and activated T cells displayed a BCP phenotype (Ig- or cytoplasmic mu+ and
      kappa/lambda-), including most of the cycling cells, indicating that the cultures
      do not favor a transition to mature B cells. Supernatants of activated T cells
      were ineffective in inducing BCP proliferation, indicating the necessity of close
      association with stimulator cells. In line with this finding, the CD40 molecule
      was found to represent an important component of the cocultures, as BCP
      proliferation was strongly inhibited by soluble anti-CD40 antibody. In addition,
      CD4+ T cell clones from a hyper-IgM patient expressing a truncated CD40 ligand
      (CD40-L) failed to induce BCP proliferation. Finally, a combination of cytokines
      (IL-2, IL-3, IL-7, and IL-10) enhanced the observed T cell-dependent BCP
      proliferation, but could not substitute for the deficient CD40-L. Taken together,
      our data demonstrate that CD4+ T cells exert a stimulatory effect on in vitro B
      human lymphopoiesis via the CD40 pathway. The present results suggest that T
      cells may play an important role in regulating B cell ontogeny in the bone
      marrow.

PMID- 7509828
TI  - Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways.
AB  - The Fas Ag and the p55 TNF receptor (TNF-R1) are related molecules that can
      signal apoptosis. Some tumor cell lines are selectively killed by Fas activation
      and others by TNF-R1 activation even though both receptors are often co
      expressed. TNF-R1-mediated cytotoxicity can be selectively inhibited under
      conditions in which Fas-mediated cell death is not affected. Activation of both
      receptors results in synergistic signaling of apoptosis. These results indicate
      that different biochemical pathways are activated by Fas and TNF-R1. Combination
      treatment with agonists of Fas and TNF-R1 may have therapeutic potential.

PMID- 7509829
TI  - Vaccination of sheep against Fasciola hepatica with glutathione S-transferase.
      Identification and mapping of antibody epitopes on a three-dimensional model of
      the antigen.
AB  - The glutathione S-transferases (FhGST) of the liver fluke Fasciola hepatica have
      been identified as novel vaccine candidates that protect sheep against a fluke
      infection. With the use of overlapping peptides covering the predicted amino acid
      sequences of four FhGST cDNAs, we have defined the linear epitopes recognized by
      polyclonal antibody from sheep vaccinated with FhGST. Dominant and minor epitopes
      were found to be present on all four of the sequences although some epitopes were
      shown to be specific to particular FhGST. A high percentage of the FhGST peptides
      were found to be antigenic although considerable variability in response to the
      peptides was observed among the animals. This analysis was extended to the IgG1
      and IgG2 response at the peptide level. Based on the recently solved crystal
      structure of the rat mu-class GST 3-3, a three-dimensional model of one of the
      FhGST sequences was generated that allowed the predicted spatial localization of
      defined epitopes. Most epitopes were localized on regions of high flexibility and
      accessibility. A comparison of epitopes on FhGST with the B cell epitopes on
      Sm28, a 28-kDa GST from Schistosoma mansoni, has found few similarities. There
      was no correlation between an antibody response to linear peptide epitopes and
      the level of protection induced in sheep by vaccination with FhGST.

PMID- 7509830
TI  - Properties of protein kinase C isoforms (beta II, epsilon, and zeta) in a
      macrophage cell line (J774) and their roles in LPS-induced nitric oxide
      production.
AB  - Northern analysis of poly(A)+ RNA extracted from J774 cells (a mouse macrophage
      cell line) showed that this cell line constitutively expresses mRNAs specific for
      protein kinase C (PKC)-beta I, -beta II, -epsilon and -zeta, but not those for
      PKC-alpha, -gamma or -delta. Western analysis of the total cell lysate showed
      that J774 cells express PKC-beta II, -epsilon and -zeta isoenzymes, but failed to
      show the expression of PKC-beta I. The exposure of J774 cells to > 10 nM PMA led
      to a loss of immunoreactive PKC-beta II in 4 h. The down-regulation of
      immunoreactive PKC-epsilon required more than 8 h of the exposure to > 100 nM
      PMA. Immunoreactive PKC-zeta was most resistant to PMA treatment and was not
      significantly reduced after the exposure to 300 to 600 nM PMA for 24 h. PMA
      mediated, persistent down-regulation of PKC-beta II is probably a result of the
      inhibition of PKC-beta II biosynthesis at the posttranscriptional level, because
      PMA-exposed cells were found to gradually increase the expression of PKC-beta II
      specific mRNA. PMA-pretreated cells responded to a low dose (10 ng/ml), but not
      to a high dose (1 microgram/ml), of LPS by significantly lower expression of mRNA
      specific for the inducible nitric oxide synthase (i-NOS) gene and production of
      nitric oxide (NO) than the control cells did. Thus, PKC could be a part of the
      signal transduction apparatus involved in LPS-induced inducible nitric oxide
      synthase gene activation.

PMID- 7509831
TI  - Monocytes use either CD11/CD18 or VLA-4 to migrate across human endothelium in
      vitro.
AB  - Monocytes traverse the endothelial lining of blood vessels and migrate into both
      normal and inflamed tissues. An in vitro model of a vascular wall, consisting of
      HUVEC cultured on acellular human amniotic tissue, was employed to examine the
      roles of several adhesion molecules in diapedesis of monocytes. Approximately
      half of the monocytes added to this system traversed the endothelium in a time
      dependent fashion, completing their migration within 2 h. Pretreatment of HUVEC
      with IL-1 beta for 4 h increased the rate of adhesion of monocytes, but did not
      alter the number that ultimately migrated. A mAb to CD18, ts1/18, greatly
      inhibited adhesion and migration of monocytes when the monocytes were incubated
      with unstimulated HUVEC monolayers for 20 min. Much less inhibition was observed
      when the incubation period was increased to 2 h or when HUVEC were pretreated
      with IL-1 beta. A mAb to VLA-4, HP1/2, had little or no inhibitory effect in all
      cases. The combination of ts1/18 and HP1/2 greatly inhibited (up to 98%) adhesion
      and migration of monocytes across both unstimulated and IL-1 beta-stimulated
      monolayers. Additional inhibition experiments indicated that VLA-4 interacted
      with unstimulated endothelium by binding to VCAM-1 and, to a much lesser extent,
      fibronectin. These results suggest that monocytes are capable of interacting with
      endothelium during diapedesis via either CD11/CD18- or VLA-4-dependent pathways.

PMID- 7509832
TI  - A synthetic peptide from complement protein C9 binds to CD59 and enhances lysis
      of human erythrocytes by C5b-9.
AB  - The membrane glycoprotein CD59 protects host cells from homologous complement
      attack by inhibiting the assembly of the membrane attack complex. CD59 binds to
      C8 and C9 in the nascent membrane attack complex and interferes with C9 membrane
      insertion and polymerization. We show here that a synthetic peptide from the
      putative C9 hinge region, postulated to be involved in the rearrangement of C9
      globular domains during membrane insertion, binds specifically to CD59 and
      enhances lysis of human erythrocytes by the terminal complement C5b-9 complex.
      The peptide, C9H, caused a dose-dependent increase in the sensitivity of human
      erythrocytes to C5b-9-mediated lysis by interfering with the final C9 binding
      and/or membrane insertion step. C9H exhibited species-specificity, since it had
      no activity against guinea pig C8 and C9 or on the putative functional homologues
      of CD59 in guinea pig erythrocytes. A direct association between CD59 and C9H was
      suggested by two different binding experiments: C9H inhibited the binding of 125I
      labeled CD59 to immobilized C9, and C9H immobilized to microtiter plates bound
      purified CD59 and selectively recognized CD59 from extracts of detergent
      solubilized human erythrocyte membranes. These data indicate that the peptide C9H
      corresponds to a region of the CD59 binding site of C9.

PMID- 7509834
TI  - Tenascin: does it play a role in epidermal morphogenesis and homeostasis?
AB  - Tenascin is a large glycoprotein of the extracellular matrix. Its complex
      multidomain structure, along with its unique distribution during embryogenesis,
      inflammation, wound healing, and tumorigenesis suggest this protein may play a
      significant role in regulating cell proliferation, migration, and
      differentiation. In this review I will summarize the structural features of
      tenascin and its localization in skin and discuss some of the potential roles of
      tenascin in the regulation of keratinocyte biology.

PMID- 7509833
TI  - Immunomorphologic studies of human decidua-associated lymphoid cells in normal
      early pregnancy.
AB  - Human decidual lymphocytes from early, normal pregnancy were characterized in
      situ with respect to ultrastructure and distribution of subsets. The
      ultrastructure of isolated decidual gamma delta T cells was also studied. CD45+
      cells comprised 11 +/- 2% of all decidual cells. The majority were localized in
      large lymphoid cell clusters (LCC), near endometrial glands, or as
      intraepithelial lymphocytes (IEL) in glandular epithelium. The major cell
      populations in LCC were CD56+TCR-gamma delta+ cells, CD56+ cells, TCR-alpha
      beta+CD4+ cells, and TCR-alpha beta+CD8+ cells. All expressed activation markers
      (CD45RO, Kp43, and/or HML-1) and MHC class II Ag (HLA-DR, HLA-DP, and/or HLA-DQ).
      No B cells were found. Almost all IEL were activated TCR-gamma delta+ cells
      (CD56+ and CD56-). The glandular epithelial cells expressed heat shock protein 60
      at the basolateral side facing the TCR-gamma delta+ IEL. Decidual lymphocytes
      displayed cytoplasmic processes, microvilli, characteristic cytoplasmic granules,
      and had intimate contact with neighboring cells. Lymphocytes in the outer rim of
      LCC and the stroma showed signs of cellular movement. Two main morphotypes of
      gamma delta T cells could be distinguished. One had single microvilli, membrane
      bound granules, and nuclear inclusions. The other had many microvilli,
      nonmembrane-bound granules and cytoplasmic multivesicular bodies. Our data
      suggest that LCC are centers of immune reactivity where T and NK cells become
      activated. The activated cells may guard against infections and undue trophoblast
      invasion and/or be involved in modulating the local maternal immune system toward
      unresponsiveness against the semiallogeneic fetus.

PMID- 7509835
TI  - Production and characterization of antibodies against human tyrosinase.
AB  - Proteins mapping at different loci are involved in melanogenesis and share
      several characteristic structural features (b locus, c locus, and slaty locus
      products). We describe a method to produce specific antibodies against human
      tyrosinase, the product of the c locus. Mouse L cells transfected with a human
      tyrosinase cDNA were used to generate antibodies by immunization of syngeneic C3H
      mice. These antibodies were able to precipitate the tyrosinase glycoprotein from
      both melanocytic cells and transfectants expressing tyrosinase. In contrast,
      transfectants expressing the related but distinct b locus protein (gp75 or TRP-1)
      did not react with these antibodies. In most cases, tyrosinase enzymatic activity
      could be precipitated and recovered in immune complexes, but one antibody
      response blocked tyrosinase activity. Immunostaining with anti-tyrosinase
      antibodies revealed an intracellular granular pattern in tyrosinase transfectants
      and melanocytic cells, but not transfectants expressing the b locus protein. This
      approach provides a general method to produce specific antibodies against
      tyrosinase, other members of the tyrosinase family of proteins, and potentially
      any other differentiation antigen.

PMID- 7509837
TI  - CD7-negative helper T cells accumulate in inflammatory skin lesions.
AB  - Recently, we identified a particular T-cell subset in the peripheral blood of
      normal individuals that lack CD7 expression. In this study we determined the
      portion of CD7- T cells in the peripheral blood and skin of patients with various
      inflammatory skin diseases. We found that skin-infiltrating lymphocytes isolated
      from different benign and malignant skin lesions (n = 20) contain a high portion
      of CD7- helper T cells, whereas the number of CD7- T cells in the peripheral
      blood was not altered compared to healthy controls. Cell activation in vitro did
      not induce CD7 expression in negative T cells but increased CD7 expression in CD7
      positive cells. Thus, lack of CD7 expression seems to be a stable characteristic
      in a major subset of skin-infiltrating lymphocytes. During long-term culture of
      CD7- helper T-cell clones derived from a psoriasis skin lesion, no phenotypic
      change in the CD7 phenotype could be monitored by sequential flow-cytometric
      analyses. No CD7 mRNA could be detected by Northern blot analysis, indicating
      transcriptional regulation of CD7 expression. The results show that CD7- T cells
      accumulate in certain inflammatory skin lesions without alteration of the
      circulating CD7- population. These cells may be identical to or derived from CD7-
      T cells of the peripheral blood.

PMID- 7509836
TI  - DNFB contact sensitivity (CS) in BALB/c and C3H/He mice: requirement for early
      occurring, early-acting, antigen-specific, CS-initiating cells with an unusual
      phenotype (Thy-1+, CD5+, CD3-, CD4-, CD8-, sIg-, B220+, MHC class II-, CD23+, IL
      2R-, IL-3R+, Mel-14-, Pgp-1+, J11d+, MAC-1+, LFA-1+, and Fc gamma RII+).
AB  - Immunization of mice for contact sensitivity induces two different antigen
      specific Thy-1+ cell activities that are required to act in sequence for
      elicitation of contact sensitivity. In this study, 2,4-dinitro-1-fluorobenzene
      contact sensitivity responses in BALB/c and C3H/He mice demonstrated the
      importance of early-acting and antigen-specific contact sensitivity-initiating
      cells to recruit the classical, late-acting contact sensitivity effector T cells.
      Employing in vitro treatment of sensitized cells with monoclonal antibodies to
      cell surface determinants and then incubation in complement, prior to adoptive
      cell transfer, the contact sensitivity-initiating cells were shown to have a
      surface phenotype that is quite unusual for antigen-specific cells [Thy-1+, CD5+,
      CD3-, CD4-, CD8-, sIg-, B220+, major histocompatibility complex class II-, CD23+,
      IL-2R-, IL-3R+, Mel-14-, CD44+ (Pgp-1+), J11d+ (HSA+), MAC-1+, LFA-1+, and Fc
      gamma IIR+], and is quite different from the late-acting, contact sensitivity
      effector T cells (Thy-1+, CD5+, CD3+, CD4+, CD8-, sIg-, B220-, major
      histocompatibility complex class II-, CD23-, IL-2R+, IL-3R-, and CD44- (Pgp-1-),
      J11d-(HSA-), MAC-1-, LFA-1+, Fc gamma IIR-). Contact sensitivity initiation was
      required for elicitation of late 24-h 2,4-dinitro-1-fluorobenzene contact
      sensitivity responses, in both BALB/c and C3H/He mice. Moreover, relatively high
      doses of some monoclonal antibodies [anti-B220 (CD45RA) and anti-CD23 (IgE Fc
      epsilon II receptor)] were necessary to completely eliminate all contact
      sensitivity-initiating cells that permitted expression of late contact
      sensitivity-effector T-cell activity. In contrast, high doses of monoclonal
      antibody specific for surface determinants of late-acting contact sensitivity
      effector T cells (anti-CD3 and anti-CD4), when used in high doses similar to anti
      B220 and anti-CD23, had no effect on contact sensitivity-initiating cell
      activity. Our results indicate that two very different antigen-specific Thy-1+
      cells are necessary to elicit 2,4-dinitro-1-fluorobenzene contact sensitivity in
      BALB/c and C3H/He mice.

PMID- 7509838
TI  - Epidermolytic hyperkeratosis: applied molecular genetics.
AB  - Epidermolytic hyperkeratosis is an autosomal dominant ichthyosis characterized by
      blistering, especially at birth and during childhood, and hyperkeratosis.
      Epidermolytic hyperkeratosis presents striking clinical heterogeneity,
      particularly between families. Several avenues of research have implicated an
      abnormality of epidermal differentiation in the pathogenesis of this disease. In
      a three-generation family with 20 affected individuals, we tested a variety of
      candidate loci and identified linkage to the type II keratin region on chromosome
      12. Further investigation revealed a mutation in the H1 subdomain of the keratin
      1 gene as the cause of EHK in this family. Because keratin 10 is the co-expressed
      partner of keratin 1, it was not surprising when abnormalities in keratin 10 were
      found in other families with EHK. We have examined 52 patients from 21 families
      and have identified at least six clinical phenotypes. The most useful
      distinguishing feature was the presence or absence of severe hyperkeratosis of
      the palms and soles. We and others are continuing to search for and characterize
      mutations in keratin 1 and 10 in patients with epidermolytic hyperkeratosis.
      Correlation of the clinical disease types with the specific mutations should lead
      to a better understanding of the relationship between keratin structure and
      function in normal and diseased epidermis.

PMID- 7509839
TI  - [Natural abundance of carbon, nitrogen, and hydrogen isotope ratios in biogenic
      substances: present and future].

PMID- 7509840
TI  - [Tertiary structural analyses of RNA using heteronuclear multidimensional NMR].

PMID- 7509842
TI  - Beta 2-adrenoceptor agonists regulate the IL-4-induced phenotypical changes and
      IgE-dependent functions in normal human monocytes.
AB  - The beta 2-adrenoceptor agonists salbutamol and fenoterol were tested for their
      regulatory effects on human monocyte phenotype and functions, either alone or in
      combination with interleukin-4 (IL-4). These drugs enhanced in a dose-dependent
      manner the IL-4-induced membrane and mRNA expression of the low-affinity receptor
      for immunoglobulin E (IgE) (CD23), as well as the release of its soluble form,
      sCD23. Salbutamol and fenoterol alone elicited expression of the monomorphic beta
      2-chain (CD18) of the leukocyte functional antigen (LFA1) family. This effect
      appeared to be restricted to CD11b (CR3) and CD11c (gp 150-95), because CD11a
      (LFA-1 alpha chain) was not modified. beta 2-Adrenoceptor stimulation was also
      found to potentiate the effect of IL-4 on CD11b, CD11c, and CD18 expression. In
      contrast, these agents alone did not alter the level of major histocompatibility
      complex class II and CD14 antigens or modify their respective up- and down
      regulation by IL-4. Ligation of CD23 on IL-4-preincubated (CD23+) monocytes with
      IgE/anti-IgE immune complexes induced the release of free radicals nitric oxide
      and of the proinflammatory mediators IL-6 and thromboxane B2 (TxB2). Addition of
      salbutamol, inactive alone, potentiated the generation of superoxide anion and of
      nitric oxide generation, as well as the production of IL-6 and TxB2 triggered by
      CD23 ligation. These results indicate that beta 2-adrenoceptor stimulation
      potentiates in vitro the IL-4-induced phenotypical and functional changes on
      monocytes and suggest that such an interaction could occur in IgE-dependent
      immune reactions.

PMID- 7509841
TI  - Regulation of interferon-alpha-inducible cellular genes in human immunodeficiency
      virus-infected monocytes.
AB  - Cellular mechanisms that control susceptibility to opportunistic infection in
      human immunodeficiency virus (HIV)-infected individuals remain poorly understood.
      HIV may induce certain cellular genes that restrict HIV replication and protect
      cells against other superinfecting viral pathogens. Indeed, HIV-infected
      monocytes resist infection by vesicular stomatitis virus (VSV). HIV-induced VSV
      interference in monocytes increases with time after HIV infection. Such
      interference was evident 6 h after HIV infection and reached maximal levels at 14
      days. Monocytotropic but not T cell-tropic HIV strains elicited these effects,
      signaling a requirement for viral entry and/or replication. Viral interference
      was independent of interferon (IFN) and was unaffected by addition of
      neutralizing IFN-alpha and -beta antibodies. The well-described IFN-alpha
      inducible antiviral pathways were examined to determine their relationship to the
      cellular mechanism(s) underlying VSV interference. HIV and IFN-alpha both induced
      the expression of 2-5A synthetase and Mx gene. In contrast, the guanylate-binding
      protein (GBP), 6-16, and 9-27 cellular genes were up-regulated by IFN-alpha but
      not HIV. MxA was detected in HIV-infected monocytes but not in uninfected
      monocytes. The association between Mx expression and resistance to VSV, coupled
      with previously described anti-VSV activities by human MxA, suggested that Mx may
      be an effector molecule for the HIV-induced anti-VSV activities. These results,
      taken together, suggest that HIV can induce antiviral cellular gene expression,
      independent of IFN.

PMID- 7509844
TI  - Macrophages and angiogenesis.
AB  - Macrophages are supposed to play a key role in inflammatory and tumor
      angiogenesis. Their importance derives from (1) their ubiquitous presence in
      normal and especially inflamed tissues, (2) their potential to become activated
      in response to appropriate stimuli, and (3) their repertoire of secretory
      products. By release of proteases, growth factors (bFGF, GM-CSF, TGF-alpha, IGF
      I, PDGF, VEGF/VPF, TGF-beta), and other monokines (IL-1, IL-6, IL-8, TNF-alpha,
      substance P, prostaglandins, interferons, thrombospondin 1), activated
      macrophages have the capability to influence each phase of the angiogenic
      process, such as alterations of the local extracellular matrix, induction of
      endothelial cells to migrate or proliferate, and inhibition of vascular growth
      with formation of differentiated capillaries. This review describes macrophage
      physiology and the influence of macrophage secretory products on the different
      phases of angiogenesis in vitro and in vivo.

PMID- 7509843
TI  - LGL-1: a potential triggering molecule on murine NK cells.
AB  - Natural killer (NK) cells mediate non-major histocompatibility complex-restricted
      lysis of tumor cells, lymphokine-activated killing (LAK), antibody-dependent
      cellular cytotoxicity (ADCC), and reverse ADCC (RADCC). LGL-1+ cells identify a
      major subset (50%) of murine NK cells. Here we demonstrate that monoclonal
      antibodies (mAbs) to LGL-1 consistently induce interleukin-2-cultured, and
      Corynebacterium parvum (in vivo)-activated NK cells to induce RADCC. LGL-1
      triggering of activated NK cells coincides with enhanced LGL-1 expression.
      Testing of murine mAbs to epitopes of CD2 only appears to augment RADCC induced
      by mAb NK-1.1 on fresh NK cells. Immunoprecipitation of the LGL-1 antigen reveals
      a highly disulfide-linked 40-kDa homodimer subunit that is N-glycosylated.
      Therefore, LGL-1 may be similar to other recently characterized NK-associated
      antigens such as NK-1.1, Ly-49, and NKR-PI. We conclude that although LGL-1 is
      expressed on "resting" NK cells, enhanced surface expression following activation
      is usually required for it to act as a signaling molecule.

PMID- 7509845
TI  - Incidence and electrophysiologic characteristics of supernormal atrial conduction
      in humans.
AB  - The incidence and electrophysiologic characteristics of supernormal atrial
      conduction (SNC) were examined by cardiac stimulation in 53 control subjects.
      Their ages ranged from 15 to 71 years (mean age, 50 +/- 21 years) (mean +/- SD).
      There were 27 women and 26 men in the study. Conduction of premature atrial
      responses from the sinus node to the atrioventricular node (intraatrial
      conduction time) was supernormal in 27 (51%) subjects and conduction to the left
      atrium (interatrial conduction time) was supernormal in 35 (66%) subjects
      (difference not significant). At coupling intervals ranging between 440 and 240
      ms, the conduction time of the premature beats was as much as 25 ms shorter than
      that of the basic driven beats. The maximum decrease in interatrial conduction
      time during the period of SNC was 13 +/- 5 ms and the maximum decrease in
      intraatrial conduction time was 9 +/- 3 ms (P < .001). The supernormal
      interatrial conduction zone was 71 +/- 29 ms and the supernormal intraatrial
      conduction zone was 57 +/- 25 ms (P < .05). There was a significant positive
      correlation between the SNC zone and the maximum decrease in conduction time (r =
      .82; P < .001). Supernormal atrial conduction was stable, reproducible, and
      remained constant in individual patients. Supernormal atrial conduction was found
      to be a relatively frequent phenomenon. There was a significantly greater SNC
      zone and maximum decrease in conduction time in interartrial conduction than in
      intraatrial conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509847
TI  - Proteolipid protein gene expression in demyelination and remyelination of the
      central nervous system: a model for multiple sclerosis.
AB  - We asked whether nonlethal injury to the oligodendrocyte as manifested by altered
      myelin gene expression is an early event in the pathogenesis of demyelinating
      disease and subsequent remyelination. Using simultaneous in situ hybridization
      and immunocytochemistry, we studied expression of proteolipid protein (PLP)
      antigen and mRNA in spinal cords of normal adult mice and of mice infected with
      Theiler's virus which provides an excellent model for multiple sclerosis.
      Downregulation of PLP mRNA was observed within 3 days and persisted for as long
      as 367 days following intracerebral virus infection of SJL/J mice which are
      susceptible to chronic demyelination. Downregulation of myelin gene products
      preceded the development of prominent inflammation and demyelination observed
      following virus infection. In contrast, no change from control uninfected mice
      was observed in the expression of PLP mRNA following infection of C57BL/10SNJ
      mice which are resistant to demyelination. Treatment of chronically infected
      susceptible SJL/J mice with a regimen which promotes CNS-type (oligodendroglial)
      remyelination resulted in a 3- to 4-fold increase in PLP mRNA expression in
      oligodendrocytes. Actin mRNA expression in PLP antigen-positive cells was
      unchanged following TMEV-induced demyelination or remyelination indicating up- or
      downregulation of myelin gene products as compared to constitutively expressed
      actin gene. These experiments support the hypothesis that early regulation of
      myelin gene expression may be an important determinant in demyelination and in
      remyelination following nonlethal injury to oligodendrocytes.

PMID- 7509846
TI  - Correlation between fibroblast growth factor expression and cell proliferation in
      experimental brain infarct: studied with proliferating cell nuclear antigen
      immunohistochemistry.
AB  - Astrogliosis, angiogenesis and macrophage activity are classical responses of
      brain to injury. The factors that induce these changes and the dynamic
      interaction among cells in the environs of the injured brain remain unclear. In
      the present rat brain infarct model, we studied the spatiotemporal relationship
      between basic fibroblast growth factor (bFGF) expression and cell proliferation
      using proliferating cell nuclear antigen (PCNA) as an S-phase marker. We
      demonstrated an early astrocytic and neuronal activation with enhanced expression
      of bFGF in areas adjacent to the infarct. This was followed by a period from 3-5
      days of intense cell proliferation. Proliferating cell nuclear antigen-labeled
      nuclei were demonstrated in perineuronal satellite cells, endothelial cells,
      vascular pericytes, macrophages and glial cells. These cells appeared to respond
      to the same mitogen(s) and they produced bFGF during the proliferative phase.
      There was a simultaneous spreading of neuronal activation and glial proliferation
      from the infarct to the entire ipsilateral hemisphere and through the coronal
      radiations to the contralateral hemisphere. This spreading follows the pattern of
      spreading of edema fluid. Our findings suggest that cell proliferation in the
      brain infarct may be induced by bFGF released by neurons and sustained by bFGF
      and other growth factors produced by non-neural cells on an autocrine basis.

PMID- 7509848
TI  - Immunohistochemical detection of myelin basic protein is a sensitive marker of
      myelination in second trimester human fetal spinal cord.
AB  - The Luxol fast blue (LFB) technique is widely used for the assessment of
      myelination. Lectin histochemistry using peanut agglutinin (PNA) has also been
      employed for this purpose. Recently, immunohistochemical methods using antibodies
      to several myelin-related proteins have been adopted to study myelination in
      humans. However, the relative sensitivities of these different methods for the
      detection of early myelination in the human fetal central nervous system have not
      been determined. Vibratome sections of cervical spinal cord from 15 human
      abortuses ranging in age from 15 to 24 gestational weeks (GW) were probed with
      immunohistochemical methods using antibodies to myelin basic protein (MBP), 2',3'
      cyclic nucleotide 3'-phosphodiesterase (CNPase), and myelin-associated
      glycoprotein (MAG). In addition, LFB and PNA histochemistry was employed. The
      degree of myelination observed in immunohistochemically stained sections was
      compared to that found in corresponding LFB- and PNA-stained paraffin-embedded
      tissues. The intensity of myelination was graded by two observers on a scale of 0
      (none), +1 (mild), +2 (moderate), and +3 (marked). At all ages examined, the MBP
      immunohistochemical method revealed more myelin than LFB or MAG staining. CNPase
      could not be reliably detected until after 18 GW. Peanut agglutinin stained
      myelin, but subpial astrocytes and the intervening neuropil were also stained.
      These results suggest that MBP is a more sensitive marker for early human fetal
      myelination than CNPase, MAG, PNA or LFB.

PMID- 7509850
TI  - Angiogenesis and breast cancer.

PMID- 7509849
TI  - Immunohistochemical staging of neurofibrillary degeneration in Alzheimer's
      disease.
AB  - Antibodies to different phosphorylated and non-phosphorylated tau epitopes have
      been used to identify three histologically distinct types of neurofibrillary
      tangles in Alzheimer's disease. Intracellular tangles (Type 1) were identified by
      antibodies recognizing epitopes throughout the tau molecule, including the NH2
      terminus. Compact extracellular tangles (Type 2) were characterized by the loss
      of NH2-terminal immunoreactivity and retention of other tau epitopes. Dispersed
      extracellular tangles (Type 3) were characterized by the presence of epitopes
      associated with the microtubule binding region and the COOH-terminus. These three
      types of tangles, found in situ in hippocampus, could be created experimentally
      by proteolytic treatment of brain sections. These findings suggest that three
      stages of neurofibrillary degeneration can be understood as a sequential
      stripping of paired helical filaments in which the loss of amino-terminus
      epitopes, followed by loss of phosphorylated epitopes, results in the appearance
      of dispersed extracellular tangles containing PHF-core epitopes.

PMID- 7509852
TI  - Sensitive detection of occult breast cancer by the reverse-transcriptase
      polymerase chain reaction.
AB  - PURPOSE: Detection of occult carcinoma in patients with breast cancer may aid the
      establishment of prognosis and development of new therapeutic approaches. To
      improve on existing methods of detection, we have developed a reverse
      transcriptase polymerase chain reaction (RT-PCR) assay for keratin 19 (K19)
      transcripts to identify mammary carcinoma cells in the peripheral blood and bone
      marrow of patients with breast cancer. PATIENTS AND METHODS: Peripheral-blood or
      bone marrow samples obtained from 34 patients with stages I to IV breast cancer
      and 39 control subjects without breast cancer were screened for K19 mRNA by
      nested primer PCR. RESULTS: In reconstitution experiments, K19 RT-PCR reliably
      detected 10 mammary carcinoma cells in 1 million normal peripheral-blood
      mononuclear (PBMN) cells. Four of 19 patients with stage IV breast cancer had
      detectable K19 transcript in peripheral blood. Five of six patients with
      histologically negative bone marrow biopsies following preablative chemotherapy
      and before autologous bone marrow transplant (BMT) were positive by this assay.
      Stem-cell apheresis harvests obtained from one of these patients and three
      additional patients immediately before BMT were all K19-negative. K19 RT-PCR
      analysis of CSF from a breast cancer patient with known carcinomatous meningitis
      was also positive. Thirty-eight of 39 non-breast cancer patients had negative K19
      RT-PCR assays. The one exception was a patient with chronic myelogenous leukemia.
      CONCLUSION: RT-PCR of K19 is a sensitive, specific, and rapid method for
      detection of occult mammary carcinoma cells in the peripheral blood and bone
      marrow of patients with breast cancer. The presence of residual breast cancer
      cells in histologically normal bone marrow aspirates but not in stem-cell
      apheresis harvests is a frequent finding. This assay may be useful in diagnosing
      metastatic disease, as well as in monitoring the effectiveness of systemic
      therapy.

PMID- 7509853
TI  - Escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin plus
      recombinant human granulocyte colony-stimulating factor in advanced urothelial
      carcinoma: an Eastern Cooperative Oncology Group trial.
AB  - PURPOSE: This multicenter cooperative group phase I/II trial evaluated the
      toxicity and efficacy of escalated dosages of methotrexate, vinblastine,
      doxorubicin, and cisplatin (M-VAC) with recombinant human granulocyte colony
      stimulating factor (rhG-CSF) in patients with advanced urothelial carcinoma.
      PATIENTS AND METHODS: From November 1990 through October 1991, 35 patients with
      advanced urothelial cancer previously untreated with chemotherapy were treated
      with escalated dosages of M-VAC (M-VACII). In patients with prior pelvic
      radiotherapy, standard M-VAC (M-VACI) was administered plus rhG-CSF. For other
      patients, M-VACII dosages were methotrexate 40 mg/m2 (days 1, 15, and 22),
      vinblastine 4 mg/m2 (days 2, 15, and 22), doxorubicin 40 mg/m2 (day 2), and
      cisplatin 100 mg/m2 (day 2). In addition, rhG-CSF was administered at a dosage of
      300 micrograms subcutaneously on days 4 to 11. Cycles were repeated every 4
      weeks. For patients who tolerated the first course of therapy, subsequent
      escalation by 25% of all drugs was performed. RESULTS: Six complete responses and
      15 partial responses were observed (60%; 95% confidence interval, 42% to 76%).
      The median duration of response was 4.6 months, and the median survival time was
      9.4 months (range, 0.5 to 23.5+). Twenty-eight of 35 patients experienced grade 3
      or 4 leukopenia, including 14 patients who developed fever associated with
      neutropenia. Eight (23%) early deaths were observed. CONCLUSION: This regimen (M
      VACII) with escalated dosages of M-VAC was associated with significant toxicity
      and had no apparent benefit over M-VACI therapy with regard to complete response
      rate or survival. Further evaluation of the dose-intensity of the components of
      this regimen in this disease is likely to be of limited benefit to patients.

PMID- 7509851
TI  - Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic
      vessel invasion are relevant prognostic markers in node-negative breast
      carcinoma.
AB  - PURPOSE: To determine the absolute and relative value of microvessel density
      (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion
      (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and
      overall survival (OS) rates in patients with node-negative breast carcinoma
      (NNBC). PATIENTS AND METHODS: We monitored 254 consecutive patients with NNBC for
      a median of 62 months. Intratumoral MVD was measured after microvessels were
      immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone
      receptors were also determined immunocytochemically. Results were analyzed by
      both univariate and multivariate statistical analysis. RESULTS: Univariate
      analysis showed that MVD was significantly predictive of both RFS (odds ratio
      [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or
      dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36;
      P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone
      receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR,
      2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P =
      .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly
      associated with OS by univariate analysis. Multivariate analysis showed that MVD
      (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI
      (P = .0033) were all significant and independent prognostic factors for RFS.
      However, only tumor size (P = .004) and MVD (P = .047) were independent
      predictors for OS. c-erbB2 expression was not associated with outcome by either
      univariate or multivariate analysis. CONCLUSION: MVD, p53 expression, PLVI, and
      tumor size are independent prognostic indicators of recurrence, which are useful
      in selection of high-risk NNBC patients who may be eligible to receive adjuvant
      therapies.

PMID- 7509854
TI  - Primary chemotherapy in rhabdomyosarcomas and other malignant mesenchymal tumors
      of the orbit: results of the International Society of Pediatric Oncology MMT 84
      Study.
AB  - PURPOSE: The MMT 84 multicentric prospective trial of the International Society
      of Pediatric Oncology (SIOP) was designed to (1) test the effectiveness of
      ifosfamide 3 g/m2 on days 1 and 2, vincristine 1.5 mg/m2 on days 1 and 14, and
      dactinomycin 0.9 mg/m2 on days 1 and 2 (IVA) repeated every 21 days; and (2)
      reduce late effects of treatment by reserving radiation therapy to the primary
      site for patients not achieving a complete response (CR) to primary chemotherapy.
      MATERIALS AND METHODS: Between 1984 and 1989, the MMT 84 study registered 34
      children with nonmetastatic rhabdomyosarcomas (RMSs) and other malignant
      mesenchymal tumors (MMTs) of the orbit in this trial. RESULTS: The 4-year event
      free survival rate is 62% +/- 9% (SD) and the 4-year survival rate 86% +/- 7%
      (SD). A total of 11 local recurrences occurred, 10 among 22 patients treated
      without initial radiation. Salvage of local failure was achieved in nine of 11
      patients with the use of radiation and additional chemotherapy, but three later
      developed distant metastases and two have died. One isolated regional lymph node
      failure has occurred, while no patient relapsed with isolated distant metastases.
      Six of 12 patients who failed are alive with no evidence of disease from 16 to 50
      months after relapse. The treatment was well tolerated in all patients, except
      for one with renal tubular acidosis and one who died of cardiotoxicity. Twelve
      patients remain in first remission without the use of radiation to the primary
      tumor from 27 to 84 months. CONCLUSION: Despite a higher incidence of local
      recurrence when treated by primary chemotherapy, early survival rates were not
      compromised and a significant number of patients avoided the late effects of
      radiation. However, longer follow-up is required to assess the ultimate outcome
      of patients treated in this manner.

PMID- 7509858
TI  - Ionic basis for endogenous rhythmic patterns induced by activation of N-methyl-D
      aspartate receptors in neurons of the rat nucleus tractus solitarii.
AB  - 1. Activation of N-methyl-D-aspartate (NMDA) receptors in caudal nucleus tractus
      solitarii (cNTS) neurons elicited endogenous rhythmic activities. We used an in
      vitro brain stem slice preparation to determine the ionic mechanisms underlying
      the generation of these activities. 2. Using intracellular recordings, we found
      several ionic conductances to be responsible for the electrophysiological
      properties of cNTS neurons. After addition of tetrodotoxin (TTX) to the
      perfusate, cNTS neurons were still able to generate action potentials (APs).
      Because these APs were suppressed by the addition of cobalt or by the reduction
      of calcium, they were likely due to calcium currents (ICa). In addition, the
      amplitude of the afterhyperpolarization (AHP) that followed a train of TTX
      resistant APs was reduced in both low-calcium and cobalt-containing saline. It
      was therefore suggested that calcium-activated potassium (IKCa) currents were
      involved in the AHP. Accordingly, application of apamin, a blocker of slow IKCa,
      also decreased the AHP. cNTS neurons exhibited a delayed excitation phenomenon,
      characterized by a ramplike depolarization that delayed the onset of neuronal
      firing, when they were depolarized from hyperpolarizing potential. The underlying
      current was presumed to be an A-current (IKA), because this phenomenon was
      suppressed during application of 4-aminopyridine (4-AP). 3. Application of NMDA
      elicited different types of discharge patterns in cNTS neurons: a repetitive
      firing at depolarized levels of membrane potential (above -60 mV) and rhythmic
      patterns characterized by either rhythmic bursting or rhythmic single discharges
      at hyperpolarized levels (within membrane potential range of -60 to -85 mV). In
      all neurons, rhythmic patterns were superimposed on oscillations of membrane
      potential. They were characterized by a sudden shift of membrane potential,
      followed by a ramp-shaped phase of depolarization that preceded spike
      elicitation. Addition of TTX to the saline did not suppress NMDA-induced
      oscillations. Therefore rhythmic patterns were not driven by synaptic mechanisms
      but resulted from endogenous properties of cNTS neurons. 4. APs superimposed on
      NMDA-induced depolarizations presented the same characteristics as those elicited
      by positive current pulses. NMDA-elicited oscillations of membrane potential were
      eliminated by removing magnesium from the saline. Therefore oscillation
      generation was based primarily on the NMDA channel properties. 5. Intrinsic
      conductances of cNTS neurons interacted with NMDA-gated conductances to shape the
      depolarization waveform. Because removal of calcium from the saline suppressed
      endogenous oscillations, ICa currents were required for the expression of
      rhythmic activities. IKCa currents were involved in the repolarization phase of
      oscillations because apamin increased the duration of the oscillations.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7509855
TI  - The importance of bleomycin in combination chemotherapy for good-prognosis germ
      cell carcinoma.

PMID- 7509856
TI  - An examination of frog myelinated axons using intracellular microelectrode
      recording: the role of voltage-dependent and leak conductances on the steady
      state electrical properties.
AB  - 1. Intracellular microelectrode current-clamp technique was used to study the
      steady-state membrane properties of single intact large primary afferent axons
      (conduction velocity > 10 m/s) attached to isolated hemisected frog spinal cord.
      2. Hyperpolarizing electrotonic potentials (ETPs) had a slow complex multiphasic
      charging. This complex charging could be approximated by two time constants: one
      in the range of 70-210 ms, the other of < 20 ms. 3. Two regions of outward and
      inward rectification hyperpolarized to the resting membrane potential were
      observed, in addition to the previously characterized outward rectification
      active at potentials depolarized to resting membrane potential. The peak and
      steady-state input resistance of these axons in tetrodotoxin Ringer solution was
      on average 65.6 +/- 21.1 and 31.1 +/- 10.8 M omega, mean +/- SE, respectively. 4.
      Application of external tetraethylammonium (10-20 mM) significantly depolarized
      the axon and decreased the outward rectification just hyperpolarized to the
      resting membrane potential. This outward rectification could also be blocked by
      external barium ions (2-10 mM). 5. Activation of an inward or anomalous
      rectification in these axons was observed 300-600 ms after the start of a current
      pulse. In addition, a depolarizing afterpotential (DAP) (1-3 mV in amplitude, 500
      ms-10 s in duration) was evident after a current pulse in which inward
      rectification had been activated. This DAP most likely reflected the slow
      inactivation of the inwardly rectifying conductance. 6. Inward rectification was
      blocked by external application of cesium ions (1-3 mM) but it was insensitive to
      external application of barium ions (2-10 mM). The blockade of the voltage
      attenuation was accompanied by a disappearance of the DAP and an increase in the
      charging time constant of the axon. This blockade resulted in a single linear
      voltage-current (V-I) relationship. Axons now had, on average, an input
      resistance of 114 +/- 19.1 M omega. 7. Reducing the concentration of external
      potassium ions increased both the peak and steady-state slope resistance.
      Reducing the external sodium concentration altered the ETPs and the V-I
      relationship little but it consistently reduced the magnitude and length of the
      DAP. These results are compatible with the hypothesis that anomalous
      rectification is a mixed ionic conductance dependent on potassium and sodium ions
      in the external media. 8. Overall, the V-I relationship of these intact axons had
      both linear and nonlinear regions reflecting the activity of numerous slowly
      activating and inactivating conductances. (ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7509859
TI  - Significance of conductances in Hodgkin-Huxley models.
AB  - 1. We explore the roles of conductances in Hodgkin-Huxley (HH) models using a
      method that allows the explicit linking of HH model input-output behavior to
      parameter values for maximal conductances, voltage shifts, and time constants.
      The procedure can be used to identify not only the parameter values most critical
      to supporting a neuronal activity pattern of interest but also the relationships
      between parameters which may be required, e.g., limited ranges of relative
      magnitudes. 2. The method is the repeated use of stochastic search to find
      hundreds or even thousands of different sets of model parameter values that allow
      a HH model to produce a desired behavior, such as current-frequency transduction,
      to within a desired tolerance, e.g., frequency match to within 10 Hz. Graphical
      or other analysis may then be performed to reveal the shape and boundaries of the
      parameter solution regions that support the desired behavior. 3. The shape of
      these parameter regions can reveal parameter values and relationships essential
      to the behavior. For instance, graphical display may reveal covariances between
      maximal conductance values, or a much wider range of variation in some maximal
      conductance values than in others. 4. We demonstrate the use of these techniques
      with simple, representative HH models, primarily that of Connor et al. for
      crustacean walking leg axons, but also some extensions of the results are
      explored using the more complex model of McCormick and Huguenard for
      thalamocortical relay neurons. Both models are single compartment. Behaviors
      studied include current-to-frequency transduction, the time delay to first action
      potential in response to current steps, and the timing of action potential
      occurrences in response to both square-wave current injection and the injection
      of currents derived from in vitro records of excitatory postsynaptic currents. 5.
      Using these simple models, we find that relatively general behaviors such as
      current-frequency (I/F) curves may be supported by very broad, but bounded
      parameter solution regions, with the shape of the solution regions revealing the
      relative importance of the maximal conductances of a model in creating the
      behavior. Furthermore, we find that a focus on increasingly specific behaviors,
      such as I/F behavior, defined by tolerances of only a few hertz combined with
      strict requirements for action potential height, inevitably leads to increasingly
      narrow, and eventually nonphysiologically narrow, regions of acceptable parameter
      values. 6. We use the Connor et al. model to reproduce the in vitro action
      potential timing responses of a rat brain stem neuron to various
      stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7509857
TI  - Nitric oxide mediates ongoing discharges in dorsal root ganglion cells after
      peripheral nerve injury.
AB  - 1. We have examined the effect of intravenously injected nitro-L-arginine methyl
      ester (L-NAME), inhibitor of nitric oxide (NO) synthase, on the ongoing
      discharges originating in dorsal root ganglia in rats. 2. Ongoing activity was
      recorded from dorsal rootlets that were responsive to electrical stimulation of
      the axotomized sciatic nerve. Resection of the nerve proximal to the neuroma did
      not appreciably influence the rate of ongoing activity. Intravenous L-NAME (100
      and 200 mumol/kg) suppressed ongoing activity both when the neuroma was intact or
      acutely resected. The effect of L-NAME was reversed by L-arginine (575 and 1,150
      mumol/kg). 3. L-NAME had no effect on ongoing activity recorded from dorsal
      rootlets in normal rats or rootlets with no sciatic input in axotomized rats. 4.
      No ongoing activity could be recorded from sciatic nerve filaments that had been
      sectioned proximally before the recording in axotomized rats, although a response
      could be elicited by mechanical stimulation of the neuroma. 5. Because peripheral
      axotomy has been shown to markedly increase the level of mRNA for NO synthase in
      dorsal root ganglion cells, the present results indicate that NO may be involved
      in the generation of spontaneous discharges in deafferentated dorsal root
      ganglia.

PMID- 7509860
TI  - Cholecystokinin-gated currents in neurons of the rat solitary complex in vitro.
AB  - 1. Ionic conductances controlled by type A and type B cholecystokinin (CCK)
      receptors were studied in neurons of the rat nucleus tractus solitarius (NTS) and
      dorsal motor nucleus of the vagus (DMNV), using intracellular and whole-cell
      patch clamp recordings in current or voltage clamp configuration during bath
      application of agonists (CCK8, CCK4, BC 264) and antagonists. 2. CCKA receptor
      related inhibition was associated with a membrane hyperpolarization and a
      decrease in input resistance that developed 2-6 min after the arrival of drug
      into the extracellular medium. These effects were induced by 5 nM CCK8 but not BC
      264 and they were blocked by the CCKA antagonist, L-364,718, but not by the CCKB
      antagonist, L-365,260. 3. CCKA receptor-related inhibition was generated by a
      potassium current that reversed at a reversal potential E(rev) of -73 +/- 1 (mean
      +/- SE) mV with bathing potassium concentration [K+]o = 6 mM and at -88 +/- 1
      with [K+]o = 3 mM, in agreement with the Nernst equation for potassium ions. 4.
      CCKB receptor-related excitation was associated with a membrane depolarization
      and an increase of the input resistance induced by the following agonists at
      threshold concentrations: CCK8 (0.2 nM) > or = BC 264 (0.4 nM) > CCK4 (10.9 nM).
      The increase of input resistance was abolished by L-365,260 and was maintained
      after blockade of the CCKA current by L-364,718. 5. CCKB receptor-related
      excitation, in the neurons (30% of cases) in which clear response reversal was
      observed, appeared to be generated by a decrease of a potassium conductance.
      Responses showed a reversal potential E(rev) of -68 +/- 4 mV with [K+]o = 6 mM
      and -89 +/- 1 mV with [K+]o = 3 mM, verifying predictions from the Nernst
      equation applied to potassium ions. However, in 70% of cases, clear reversal was
      not observed at membrane potentials negative to the theoretical potassium
      equilibrium potential EK. 6. In voltage clamp studies, CCK8 induced a 181 +/- 17
      pA inward current associated with a 26 +/- 4% decrease in the instantaneous
      current (I(ins)) generated by hyperpolarizing voltage steps. This effect on
      I(ins) was demonstrated in the absence of effects on the outward noninactivating
      potassium current (IM) and on the inward noninactivating cationic current (IQ).
      7. CCKB receptor-mediated excitation was not suppressed by cobalt, a blocker of
      calcium currents, and was not associated with a change of the calcium-dependent
      potassium current (IK(Ca)).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7509862
TI  - Presynaptic inhibition by GABA is mediated via two distinct GABA receptors with
      novel pharmacology.
AB  - Mechanisms of presynaptic inhibition were examined in giant presynaptic terminals
      of retinal bipolar neurons, which receive GABAergic feedback synapses from
      amacrine cells. Two distinct inhibitory actions of GABA are present in the
      terminals: a GABAA-like Cl conductance and a GABAB-like inhibition of voltage
      dependent Ca current. Both of the receptors underlying these actions have unusual
      pharmacology that fits neither GABAA nor GABAB classifications. The GABA
      activated Cl conductance was not blocked by the classical GABAA antagonist
      bicuculline, while the inhibition of Ca current was neither mimicked by the GABAB
      agonist baclofen nor blocked by the GABAB antagonist 2-hydroxysaclofen. The
      "GABAC" agonist cis-4-aminocrotonic acid (CACA) both activated the Cl conductance
      and inhibited Ca current, but the inhibition of Ca current was observed at much
      lower concentrations of CACA (< 1 microM) than was the activation of the Cl
      conductance (K1/2 = 50 microM). Thus, by the criterion of being insensitive to
      both bicuculline and baclofen, both GABA receptors qualify as potential GABAC
      receptors. However, it is argued on functional grounds that the two GABA
      receptors coupled to Cl channels and to Ca channels are best regarded as members
      of the GABAA and GABAB families, respectively.

PMID- 7509861
TI  - Synaptic properties of serotonergic growth cones in developing rat brain.
AB  - In order to gain insight into the events that take place when serotonergic growth
      cones are remodeled into synapses, we tested the hypothesis that neurotransmitter
      related properties of presynaptic terminals are already present in these growth
      cones before synaptogenesis begins. The ontogeny of markers for the specific
      reuptake of 5-HT and for 5-HT-storing synaptic vesicles was studied in isolated
      growth cone (IGC) fractions from developing rat brain. High-affinity 3H
      imipramine binding (a marker for the plasma membrane 5-HT transporter) was
      significantly enriched in IGC fractions prepared before the beginning of cortical
      synaptogenesis [embryonic day 15 (E15) and E20]. Radioautography with 3H
      imipramine or 3H-paroxetine (another marker for the transporter) confirmed that
      the 5-HT transporter is present in the cerebral cortex when it contains
      serotonergic growth cones, but not serotonergic synapses. Specific uptake of 3H-5
      HT was found in IGC fractions as early as E15; this uptake was inhibited by
      fluoxetine. Electron microscopic radioautography demonstrated directly that
      growth cones were the structures in IGC fractions that took up 3H-5-HT. The
      synaptic vesicle protein synaptophysin and a 45 kDa protein found specifically in
      serotonergic synaptic vesicles, serotonin-binding protein (SBP), were each
      enriched in IGC fractions from E15 to postnatal day 5; SBP immunoreactivity
      increased approximately 10-fold between E15 and E20. Endogenous 5-HT was detected
      in IGC fractions at E15 and increased in amount as development proceeded. The
      ratio of 5-HT to 5-hydroxyindole acetic acid suggested that 5-HT within growth
      cones is protected from catabolism by monoamine oxidase. Reserpine-induced
      depletion of 5-HT, a marker for the vesicular carrier of 5-HT, was apparent in
      IGC fractions at E20, but not at E15. These data suggest that properties that
      characterize the presynaptic components of mature serotonergic synapses develop
      in growth cones before synapses are formed. The early development of these
      properties may permit neurotransmission to be established rapidly during
      synaptogenesis or, alternatively, enable 5-HT to play a role in ontogeny.

PMID- 7509865
TI  - Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.
AB  - We have examined several aspects of neurotransmitter function in the brains of
      mice carrying a deletion mutation in the gene encoding the purine salvage enzyme
      hypoxanthine-guanine phosphoribosyltransferase (HPRT). During the first 6 weeks
      of postnatal development, dopamine levels in whole-brain extracts from the mutant
      mice (HPRT-) failed to increase at rates comparable to normal animals, resulting
      in 40% lower dopamine levels throughout adulthood. Regional analysis in adult
      animals showed the caudoputamen to be the most severely affected region, with
      dopamine deficits of 48-64%. Dopamine levels in other regions were normal or less
      severely affected. The decrease in dopamine was accompanied by a decrease in
      tyrosine hydroxylase (TH) activity, the rate-limiting step in dopamine synthesis.
      Kinetic analysis of TH extracted from the caudoputamen of normal and HPRT- mice
      demonstrated a 45% decrease in Vmax with an increased affinity for the
      tetrahydropterin cofactor in the mutants. Labeling of midbrain dopamine neurons
      using TH immunohistochemistry revealed no obvious deficits in the number of
      midbrain dopamine neurons, but quantitative autoradiographic studies revealed
      significant reductions in the binding of 3H-N-[1-(2
      benzo(beta)thiophenyl)cyclohexyl]piperidine (3H-BTCP) to dopamine uptake sites in
      the forebrain of the mutants. In contrast to these abnormalities of the dopamine
      systems in the mutant mice, other neurotransmitter systems appeared relatively
      unaffected. Norepinephrine, 5-HT, tryptophan hydroxylase, and glutamic acid
      decarboxylase were present at normal levels in the brains of the mutants. ChAT
      activity was slightly lower than normal in the caudoputamen of the mutant
      animals, but was normal in all other brain regions examined. These results
      indicate that HPRT deficiency is associated with a relatively specific deficit in
      basal ganglia dopamine systems that emerges during the first 2 months of
      postnatal development.

PMID- 7509864
TI  - Development of subcellular mRNA compartmentation in hippocampal neurons in
      culture.
AB  - Neurons possess an RNA transport system that is present in dendrites (but not
      axons) and sort mRNAs so that some mRNAs are restricted to cell bodies while a
      few others (like the mRNA for MAP2) are present in dendrites. The present study
      evaluates when dendrite-specific RNA transport and mRNA sorting into cell body
      and somatodendritic compartments first appear in developing hippocampal neurons
      maintained in culture. A 3H-uridine pulse-chase paradigm was used to evaluate
      transport of newly synthesized RNA from the site of synthesis in the nucleus into
      the developing neurites. The intracellular distribution of mRNAs encoding actin,
      tubulin, GAP-43, and MAP2 as well as polyA RNA and rRNA was evaluated by in situ
      hybridization at different stages of development. Newly synthesized RNA was
      translocated into both developing axons and dendrites early in development, but
      only into dendrites as the neurons matured. Tubulin, GAP-43, and actin mRNAs,
      which are restricted to cell bodies in mature neurons, were found exclusively in
      neuronal cell bodies at all developmental stages. MAP2 mRNA, which is present in
      the dendrites of mature neurons, was present at very low levels in neurons at 2
      or 3 d in culture and was not detectable within dendrites. The overall levels of
      MAP2 mRNA increased over time, and by 5-7 d in culture, MAP2 mRNA was detectable
      in some dendrites. PolyA RNA and rRNA were detectable in developing neurites
      including axons. Levels of polyA and rRNA increased in dendrites as neurons
      matured while labeling of axons diminished. By 10 d in culture, axonal labeling
      for polyA and rRNA had virtually disappeared. The increase in the levels of
      polyA, rRNA, and MAP2 mRNA in dendrites between 5 and 7 d in culture corresponds
      roughly with the appearance of other dendritic characteristics and the beginning
      of dendritic outgrowth.

PMID- 7509866
TI  - Peptidyl carbamates as novel elastase inhibitors: structure-activity relationship
      studies.
AB  - Twenty-six novel peptidyl carbamates and thiocarbamates were synthesized and
      evaluated as elastase inhibitors. Eighteen compounds inhibited porcine pancreatic
      elastase, whereas only eleven of the newly synthesized compounds inhibited human
      leukocyte elastase. Neither of the other serine dependent proteases, trypsin or
      chymotrypsin, were affected by any of the active inhibitors. Structure-activity
      relationship studies indicated that inhibition was dependent on P1 and P'1
      substitution as well as on the presence of the carbamate functionality. Placement
      of an isostere of valine at P1 and a 1-(phenyl mercaptotetrazole at P'1 resulted
      in the most active human leukocyte elastase inhibitor within this series of
      compounds (Ki - 3.0 x 10(-7) M).

PMID- 7509863
TI  - Phosphorylation of AMPA-type glutamate receptors by calcium/calmodulin-dependent
      protein kinase II and protein kinase C in cultured hippocampal neurons.
AB  - Phosphorylation of glutamate receptors (GluRs) is emerging as an important
      regulatory mechanism. In this study 32P labeling of non-NMDA GluRs was
      investigated in cultured hippocampal neurons stimulated 2-15 min with agonists
      that selectively stimulate either Ca2+/calmodulin-dependent protein kinase II
      (CaM-kinase II), Ca2+/phospholipid-dependent protein kinase C (PKC), or cAMP
      dependent protein kinase A (PKA). Treatment of hippocampal neurons with
      glutamate/glycine (Glu/Gly), ionomycin, or 12-O-tetradecanoylphorbol 13-acetate
      (TPA) increased 32P labeling of immunoprecipitated alpha-amino-3-hydroxy-5-methyl
      4-isoxazoleproprionate (AMPA)-type GluRs by 145%, 180%, and 227%, respectively,
      of control values. This increased phosphorylation of GluRs was predominantly 32P
      Ser with little 32P-Thr and no detectable 32P-Tyr. Glu/Gly and ionomycin, but not
      TPA, also increased 32P labeling of CaM-kinase II by 175% and 195%, respectively,
      of control values. Of these three agonists, only TPA stimulated phosphorylation
      of MARCKS (225% of control), a specific substrate of PKC. Forskolin treatment
      gave a three- to fourfold increase in the active catalytic subunit of PKA but did
      not result in the 32P labeling of AMPA-type GluRs, CaM-kinase II, or MARCKS.
      Phosphorylation of GluRs in response to Glu/Gly was blocked by a specific NMDA
      receptor/ion channel antagonist (DL-2-amino-5-phosphonovaleric acid) or by a cell
      permeable inhibitor of CaM-kinase II (1-[N,O-bis(1,5-isoquinolinesulfonyl)-N
      methyl-L-tyrosyl]-4- phenylpiperazine, KN-62). These results are consistent with
      the hypothesis that Ca2+ influx through the NMDA-type ion channel can activate
      CaM-kinase II, which in turn can phosphorylate and regulate AMPA-type GluR ion
      channels (McGlade-McCulloh et al., 1993).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509867
TI  - Indirect strong inhibition by acid-stable trypsin-plasmin inhibitor (ASTPI) of
      the activations of elastase and plasma fibrinolysis in a dog model of acute
      pancreatitis.
AB  - Acid-stable trypsin-plasmin inhibitor (ASTPI) had almost no direct effect on the
      increased levels of the plasma enzymes elastase, plasmin and plasminogen
      activators in an acute pancreatitis model in the dog, whereas it strongly
      inhibited the activation of such enzymes by intravenous administration. In vivo
      experiments also showed strong inhibition by ASTPI of pancreas tissue elastase
      and plasma fibrinolysis. Anti-shock and anti-pancreatitis effects of ASTPI
      observed in clinical therapy may be related to this "indirect inhibition".

PMID- 7509868
TI  - 1-pentyl-3-(4-aminophenyl)pyrrolidine-2,5-dione, a selective aromatase inhibitor:
      in vivo studies.
AB  - 1-Pentyl, 1-hexyl and 1-heptyl-3-(4-aminophenyl)pyrrolidine-2,5-dione, potent
      inhibitors of aromatase, lower oestrogen levels in PMSG-stimulated female rats in
      a comparable manner to the inhibitor aminoglutethimide (AG) used clinically for
      the treatment of breast cancer. Pharmacokinetic studies in the rat show t 1/2
      values for the 1-hexyl compound and AG of 1.8 and 5.5 h respectively. In 4 tests
      for CNS-depressant activity the overall order of activity was AG > 1-heptyl = 1-
      hexyl >> 1-pentyl. The 1-pentyl compound has less tendency than AG to depress
      white cell and platelet counts in mice and overall is the drug candidate for
      further studies.

PMID- 7509869
TI  - Synthesis and the antiperoxidase activity of seleno analogues of the antithyroid
      drug propylthiouracil.
AB  - The synthesis of 6-n-propyl-2-selenouracil (PSeU, Ib) and its methyl derivative
      (MSeU, Ic) are described. Replacement of the sulfur atom at C2 by selenium
      increased with antiperoxidase activity of these analogues five fold when compared
      to the clinically used antithyroid drug propylthiouracil (PTU). The structure
      activity relationships of these agents are discussed.

PMID- 7509870
TI  - A method for counting active sites of cyclic AMP-dependent protein kinase.
AB  - A method has been developed for counting active sites of cyclic-AMP-dependent
      protein kinase. Known concentrations of a synthetic peptide similar to a fragment
      of the endogenous inhibitor of the kinase were included in otherwise routine
      assay mixes containing several different volumes of enzyme stock solution. The
      concentration of active sites of the catalytic subunit of the cyclic AMP
      dependent protein kinase in the stock solution was then determined by fitting
      observed velocities to an equation that accounts for the presence of a tight
      binding inhibitor. The method yielded estimates of catalytic subunit
      concentration comparable with those derived from more traditional measures of
      catalytic subunit concentration. Both purified and heterogeneous samples were
      assayed, since active-sites counting assumes only a mutually specific, high
      affinity interaction between enzyme and inhibitor and does not require that
      samples be pure. In principle, the method can be adapted to other protein kinases
      for which a specific, tight-binding, reversible inhibitor is available.

PMID- 7509871
TI  - Peptidyl ammonium methyl ketones as substrate analog inhibitors of proline
      specific peptidases.
AB  - Prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DP IV) are serine enzymes
      cleaving highly specific prolyl peptide bonds. Both enzymes were found to be
      inhibited by newly designed peptidyl ammonium and pyridinium methyl ketones
      acting as slow binding inhibitors. The most potent inhibitor of PEP is Z-Pro-Pro
      CH2N+C5H5 exhibiting a Ki* value of 1.8 nM with a first-order rate constant of
      Kon 0.0022 s-1 for the formation of the tight enzyme-inhibitor complex. DP IV and
      H-Pro-Pro-CH2N+ (CH3)3 form an enzyme-inhibitor-complex with an apparent second
      order rate constant of 2713 M-1 s-1. In contrast to the very stable N-terminal
      protected Z-Pro-Pro-CH2N+ (CH3)3, the deblocked derivative decomposes rapidly in
      aqueous solution.

PMID- 7509872
TI  - Enzyme selectivity analyses of arylsulfonylamino acid aldose reductase
      inhibitors.
AB  - Arylsulfonylamino acids, displaying a wide range of inhibitory activities versus
      rat lens aldose reductase (RLAR), were analyzed for enzyme selectivity in several
      test systems. These RLAR inhibitors were found not to produce significant
      inhibition of genetically-linked reductases (aldehyde reductase, ALR),
      catalytically similar reductases (Pachysolen tannophilus xylose reductase, PTXR),
      functionally distinct oxidoreductases (glutathione reductase, GR, lactate
      dehydrogenase, LDH, and gamma-transaminase, GABA-T), and thymidylate synthase
      (TS). These data suggest that aldose reductase differs significantly from other
      oxidoreductases in its inhibitor binding domain(s). Furthermore, the aldose
      reductase selectivity demonstrated by the arylsulfonylamino acids suggests that
      these compounds may not inhibit other key metabolic transformations in various
      cell types and that they may function as selective probes for studies of the
      relationship between aldose reductase mediated biochemical changes and the
      pathologies of chronic diabetes.

PMID- 7509874
TI  - Pediatric nurse practitioners and educational mainstreaming.
AB  - Educational mainstreaming provides an opportunity for a developmentally delayed
      child to interact in an environment with nondelayed children. It fosters growth
      by providing opportunities that other methods of education do not have.
      Mainstreaming can be initiated by the pediatric nurse practitioner. As the result
      of the developmental assessment skills of the practitioner, early intervention, a
      plan of care, referral, and ongoing evaluation can be accomplished. This article
      looks at the pros and cons of mainstreaming, at reaching a compromise on
      mainstreaming, at legislation affecting the developmentally delayed child, and at
      how the pediatric nurse practitioner can use the integrated multidisciplinary
      model with these children with special needs.

PMID- 7509873
TI  - Inhibition of aminopeptidases by phosphonic acid and phosphinic acid analogues of
      aspartic and glutamic acids.
AB  - More than 30 phosphonic and phosphinic acid analogues of aspartic and glutamic
      acids were synthesized in order to probe how the structural differences of these
      molecules were reflected in their ability to inhibit cytosolic (LAP) and
      microsomal (APM) aminopeptidases. Although most of the compounds studied were
      found to exert only a modest inhibitory effect, the studies provide some
      information on the structural requirements of the binding subsites and catalytic
      centers of both enzymes.

PMID- 7509875
TI  - Adenosine-activated potassium current in smooth muscle cells isolated from the
      pig coronary artery.
AB  - 1. The perforated patch technique with nystatin or amphotericin was used to
      record whole cell currents activated by adenosine in smooth muscle cells isolated
      enzymatically from pig coronary arteries. 2. Adenosine (5-40 microM) activated an
      outward current at a holding potential of 0 mV in 5 mM [K+]o and an inward
      current at -60 mV in 143 mM [K+]o. The dependence of the reversal potential for
      the adenosine-activated current on [K+]o suggests that it flows through K+
      channels, while its current-voltage relation is consistent with the channels
      showing little voltage dependence. 3. The adenosine-activated current was
      inhibited by the sulphonylurea glibenclamide (5 microM) and by phencyclidine (5
      microM). It was unaffected by charybdotoxin (50 nM) or apamin (100 nM), blockers
      of large and small conductance Ca(2+)-activated K+ channels respectively. 4. At 
      60 mV in 143 mM K+ solution, openings of single channels passing a current of
      just over -2 pA could sometimes be detected in the absence of adenosine. Openings
      became more frequent after the application of adenosine, with several levels then
      being detected. Openings of channels with a larger conductance were sometimes
      also seen in the presence of adenosine. Fluctuation analysis gave somewhat lower
      estimates of unitary current than did direct measurements. 5. The effect of
      adenosine could be mimicked by the A1 receptor agonist CCPA (2-chloro-N6
      cyclopentyladenosine), while the A2 agonist CGS 21680 (2-p-(2
      carboxethyl)phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride) was
      without effect. The response to adenosine was inhibited by the A1 antagonist
      DPCPX (8-cyclopentyl-1,3-dipropylxanthine), but was unaffected by the A2
      antagonist CGS 15943A (5-amino-9-chloro-2-(2-furanyl)-1,2,4- triazolo[1,5
      C]quinazoline monomethanesulphonate). 6. Our results suggest that adenosine acts
      at an A1 receptor to activate K+ channels. We consider it most likely that these
      are ATP-dependent K+ channels. We discuss the mechanism by which K+ channel
      activation may lead to hyperpolarization and so vasorelaxation.

PMID- 7509878
TI  - Copper complexation by 3-hydroxypyridin-4-one iron chelators: structural and iron
      competition studies.
AB  - Clinical trials of 1,2-dimethyl-3-hydroxypyridine-4-one (1) as an orally
      available iron chelator are presently underway in several centers. Discrepant
      reports of toxicity in human and animal studies have stimulated debate on the
      role of iron status and the availability of iron for chelation relative to other
      essential elements like copper in determining the clinical effects of 1.
      Therefore, we investigated the ability of 1, its 1,2-diethyl analog 2, and their
      iron chelates to complex copper. Both compounds formed tetracoordinate 2:1 Cu(II)
      complexes which X-ray structure analysis showed to be planar and coordinated
      through the oxygen atoms of the hydroxy ketone functionality. Potentiometric
      analysis revealed that these complexes dominated at physiological pH, although
      between pH 6 and 7 approximately equal amounts of the mono and bis complexes of
      Cu with 1 were present at equilibrium. Comparing the stepwise formation constants
      deduced from the stability constants of these complexes (log beta 2 = 21.7 +/-
      0.8 (1) and 20.2 +/- 2.0 (2)) with those of their Fe(III) complexes
      (Motekaitis,R.J.;Martell,A.E.Inorg.Chim.Acta 1991, 183,71-80) leads to a
      prediction of insignificant copper complexation when equimolar iron is present
      and dissociation products are thermodynamically unimportant. However,
      displacement of Fe3+ occurred from both complexes with stoichiometric amounts of
      Cu2+, implicating the participation of metal hydrolysis products in the
      equilibria. We conclude that Cu(II) complexes of the 3-hydroxypyridin-4-one
      chelators are stable under physiological conditions and that copper can effect
      displacement of iron by these agents under circumstances where hydrolysis of the
      metals is important.

PMID- 7509876
TI  - Alpha-fetoprotein in diabetic pregnancy. A reassessment.
AB  - We correlated glycosylated hemoglobin (HbA1) with maternal serum alpha
      fetoprotein (MSAFP) in 92 and amniotic fluid AFP (AFAFP) in 27 patients with
      pregestational and gestational diabetes. MSAFP and AFAFP were measured between 15
      and 20 weeks and correlated with HbA1. In group 1, HbA1 was measured at < or = 12
      weeks' gestation; in group 2, it was measured 0-6 weeks before MSAFP measurement;
      and in group 3, it was measured within 6 weeks after MSAFP. Mean MSAFP was 1.02
      +/- 0.77 multiples of the median (MOM) (+/- SD) in all diabetics, 1.1 +/- 0.93
      MOM in gestational diabetics and 0.89 +/- 0.33 MOM in pregestational diabetics (P
      = NS). There was no correlation between MSAFP and HbA1 in groups 1-3. Patients
      with HbA1 > 9 g% had a mean MSAFP of 0.84 MOM as compared to 0.85 MOM in those
      with HbA1 < 9 g% (P = NS). AFAFP values were within normal limits even in
      patients with HbA1 > 9 g% in early pregnancy (n = 8). No significant decrease in
      MSAFP was seen in pregestational diabetics, and no correlation was seen with HbA1
      levels. AFAFP levels were unchanged in diabetics.

PMID- 7509877
TI  - Novel series of TSAO-T derivatives. Synthesis and anti-HIV-1 activity of 4-, 5-,
      and 6-substituted pyrimidine analogues.
AB  - Several 4-, 5-, and 6-substituted pyrimidine analogues of the new anti-HIV-1 lead
      compound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]thymine] 
      3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO-T) have been
      prepared and evaluated as inhibitors of HIV-1 and HIV-2 replication in cell
      cultures. Reaction of 1,2-di-O-acetyl-5-O-benzoyl-3-C-cyano-3-O-mesyl-D
      ribofuranose with 5-substituted pyrimidine bases, followed by treatment with
      Cs2CO3, afforded, stereoselectively, beta-D-ribofuranosyl-3'-spironucleosides.
      2',5'-O-Deacylation and subsequent treatment with tert-butyldimethylsilyl
      chloride gave the TSAO-5-substituted pyrimidine derivatives. Reaction of 5
      halogen-TSAO derivatives with nucleophiles gave 6-substituted-TSAO analogues.
      Treatment of TSAO-pyrimidine analogues with POCl3/1,2,4-triazole and methylamine
      or di-methylamine afforded the 4-substituted pyrimidine compounds. Several
      substituted TSAO-thymine, TSAO-uracil, and TSAO-cytosine derivatives were found
      to be superior to their unsubstituted TSAO congeners with regard to their
      antiviral and/or cytotoxic properties.

PMID- 7509879
TI  - Reflectance in situ hybridization (RISH): detection, by confocal reflectance
      laser microscopy, of gold-labelled riboprobes in breast cancer cell lines and
      histological specimens.
AB  - A method for reflectance in situ hybridization (RISH) is presented. The
      importance of the method is demonstrated by results obtained on cytological and
      histological breast cancer specimens. Scattering reflectance signals from 1-nm
      colloidal-gold particles after RNA/RNA in situ hybridization, using digoxigenin
      labelled riboprobes, were detected by confocal scanning laser microscopy. The
      mRNA expression of two ras-related genes, rho B and rho C, was analysed in human
      histological breast cancer specimens and in human breast cancer cell lines.
      Horizontal (x, y) and vertical (z) optical sections after three-dimensional
      imaging were used for visualization. A marked heterogeneity (between individual
      cells and between specimens) was noted for the expression of the rho B gene, both
      in cytological and in histological samples. On the other hand, rho C was always
      expressed and showed no heterogeneity. This method allows the identification of
      several cellular constituents in an heterogeneous tissue structure, as
      demonstrated by the simultaneous detection of rho B (or rho C) by reflectance and
      of DNA, cytokeratin and/or vimentin by fluorescence.

PMID- 7509880
TI  - Semiautomated methods for cancellous bone histomorphometry using a general
      purpose video image analysis system.
AB  - Semiautomated methods are used to measure elongated, curved and complex branching
      profiles and isolated perimeter segments in monochrome video images with a
      general-purpose analysis system. These methods are used to make the major primary
      measurements of bone histomorphometry. Accuracy and reproducibility of the image
      acquisition, processing and measurement system is documented by measuring a
      semicircular standard of known dimensions. Semiautomated applications of the
      Ar/Le method for measuring areas and perimeters, and calculating lengths and
      widths of osteoid seams, lengths of mineralization labels and mineral apposition
      rate, wall width, indirect measurements of eroded, osteoclastic and osteoblastic
      perimeters without tracing, and measurement of mineralized or total cancellous
      bone area and perimeter gave values comparable to measurements of the same
      parameters by tracing or grid counting techniques with equal or better
      reproducibility and much greater efficiency. Intraindividual variation in
      measuring multiple bone biopsies methods. Major sources of variability for semi
      automated methods were image magnification and selection of profile edges by
      thresholding, and sources of variability for manual methods are image
      magnification, numbers of orthogonal intercepts, tracing speed and accuracy of
      the algorithm used to measure traced pixels. Semiautomated methods are accurate,
      reproducible and rapid methods suitable for bone histomorphometry.

PMID- 7509881
TI  - Peptide antibiotics of the tuberactinomycin family as inhibitors of group I
      intron RNA splicing.
AB  - The tuberactinomycins are a group of cyclic peptide antibiotics, which are potent
      inhibitors of prokaryotic protein synthesis. We report the inhibitory effect of
      viomycin, di-beta-lysyl-capreomycin IIA and tuberactinomycin A on group I intron
      self-splicing. They compete with the guanosine cofactor for the G-binding site
      located in the conserved core of the intron. They are 100-fold more active than
      all other competitive inhibitors described so far (dGTP, arginine or
      streptomycin), inhibiting splicing at concentrations between 10 and 50 microM.
      Mutation of the G-binding site leads to partial resistance, and the inhibitory
      effect of these drugs is dependent on Mg2+ concentration. This suggests that the
      tuberactinomycins have more than one contact site with the intron RNA: via the G
      binding site and via additional contacts with the RNA backbone. Positioning the
      tuberactinomycins in the three-dimensional model of the td intron core suggests
      that the charged lysyl side-chain (R1) is in contact with the backbone of the P1
      helix. Structure/function analyses with various tuberactinomycin analogues with
      different activities confirm the involvement of this sidechain in inhibition of
      group I self-splicing. The demonstration of a new class of splicing inhibitors,
      the peptide antibiotics, illustrates how antibiotics may interact with catalytic
      RNA.

PMID- 7509883
TI  - Agranulocytosis.

PMID- 7509884
TI  - [Hypervolemic hemodilution therapy for clinical vasospasm after aneurysmal
      subarachnoid hemorrhage].

PMID- 7509882
TI  - Comparative changes in microvasculature and bone during healing of implant and
      extraction sites.
AB  - The acquisition and maintenance of biological fixation of dental implants are
      achieved by a rapid and regenerative response of the recipient tissues,
      especially the vascular and osseous elements. This sequential response is
      described from initial osteogenesis through remodeling up to 20 weeks after
      implantation in Macaca fuscata monkeys. The sequential changes in the
      microvasculature and bone formation in three-dimensional bone-vasculature
      microcorrosion casts are studied by means of a plastic injection method devised
      by the author. Micrographs derived from microcorrosion casts reveal that all soft
      tissues (blood vessels walls, marrow, collagen fiber cells and the like) have
      been digested, leaving spaces once occupied by these elements, bone, and
      polymeric material that filled the blood vessels at death. The effects of
      biomaterial choice, general implant configuration, and interface configuration
      and material were sequentially analyzed. The effects of one- and two-stage
      healing variables were not analyzed. The Macaca fuscata monkeys were used for SEM
      examination of both bioinert and bioactive dental implant materials. The
      objective of this paper is to describe osseous healing at an implant interface,
      and compare it with osseous healing in tooth extraction sockets by use of a
      similar research approach in identical animal models.

PMID- 7509885
TI  - [Capsular/putaminal aphasia syndromes].

PMID- 7509887
TI  - Effects of MKS-492 on antigen-induced bronchoconstriction and allergic reaction
      in guinea pigs and rats.
AB  - Effects of R[+]-8-([1-[3,4-dimethoxyphenyl]-2-hydroxyethyl]amino) -3,7-dihydro-7
      [2-methoxyethyl]-1,3-dimethyl-1H-purine-2,6-dione (MKS-492), a reported type III
      isozyme inhibitor of cyclic nucleotide phosphodiesterase, on antigen- or platelet
      activating factor (PAF)-induced bronchoconstriction and allergic reactions in
      guinea pigs and rats were investigated. 1) MKS-492 inhibited antigen-induced
      bronchoconstriction in guinea pigs. Aminophylline also inhibited the reaction. 2)
      MKS-492 inhibited PAF-induced bronchoconstriction and inhibited the increase in
      airway responsiveness to histamine in guinea pigs, although aminophylline failed
      to affect these reactions. 3) MKS-492 relaxed guinea pig tracheal muscle in vitro
      more potently than aminophylline. 4) MKS-492 inhibited leukotriene B4 (LTB4)
      induced airway eosinophilia in guinea pigs. 5) MKS-492 inhibited passive
      cutaneous anaphylaxis and mediator-induced skin reactions in rats more potently
      than aminophylline. Both drugs inhibited antigen- and phospholipase A2-induced
      histamine release from guinea pig lung tissue. 6) MKS-492 inhibited PAF-induced
      O2- generation from guinea pig alveolar macrophages. These results indicate that
      MKS-492 is a more potent inhibitor of allergic bronchoconstriction and PAF- or
      LTB4-induced inflammatory reactions in guinea pigs and the allergic cutaneous
      reactions in rats when compared to aminophylline.

PMID- 7509886
TI  - [The evaluation of the newly produced assay kit for the cytokeratin fragment,
      "ball ELSA CYFRA21-1"].
AB  - We evaluated the newly produced tumor marker assay kit, "Ball ELSA CYFRA21-1",
      which detects cytokeratin 19 fragment in the sera of patients with malignancies,
      especially lung cancers. The assay procedure is simple based on the one-step
      radioimmunometric assay method. The measured values depend somewhat on incubation
      temperature and time. Reproducibility and recovery were good. The minimum
      measurable level was 1 ng/ml. The dilution test was satisfactory. The CYFRA21-1
      levels were gradually decreased by repeated freezing and thawing and after seven
      such exercises its activity dropped to about 70% of that of first assay. The
      presence of CYFRA21-1 antigen was strongly correlated with TPA antigen and,
      although some discrepancies could be observed in clinical samples, CYFRA21-1
      activity was completely absorbed by anti-TPA antibody-coated beads in one sample.
      CYFRA21-1 levels of 44 normal controls were below 1.0 ng/ml. Assuming a cut-off
      value of 2.0 mg/ml, 32.7% of all cases with benign disease had values greater
      than 2.0 ng/ml. This fell to 21.4% on exclusion of cases of interstitial
      pulmonary disease. Those with malignant diseases had high CYFRA21-1 levels
      whether associated with lung cancer or not. The most high positive ratios were
      observed in squamous cell lung cancer, small cell lung cancer, and uterine
      cervical cancer. In conclusion, CYFRA21-1 may be a good tumor marker comparable
      to TPA not only for lung cancer but also other malignancies as well. High false
      positives for lung cancer, however, were observed in other pulmonary diseases.

PMID- 7509888
TI  - Carbachol-induced potassium release in rat parotid acini: comparison of the roles
      of cytosolic Ca2+ and protein kinase C.
AB  - Carbachol (CCh) stimulated K+ release from rat parotid acini. Treatment with the
      intracellular Ca2+ antagonist 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate
      (TMB-8) or the intracellular Ca2+ chelator 1,2-bis(O-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA) strongly suppressed the CCh-induced K+
      release. Combined addition of the Ca2+ ionophore ionomycin and the microsomal
      Ca(2+)-ATPase inhibitor thapsigargin caused a rapid increase in cytosolic Ca2+
      concentration ([Ca2+]i) and resulted in a marked release of K+. In the absence of
      extracellular Ca2+, CCh or a combination of ionomycin and thapsigargin caused a
      transient release of K+ which correlated well with the transient change in
      [Ca2+]i. On the other hand, phorbol 12-myristate 13-acetate (PMA) did not
      potentiate the CCh-induced K+ release, although the CCh-induced amylase release
      was significantly enhanced in the presence of PMA. Staurosporine, a protein
      kinase C-inhibitor, did not inhibit the CCh-induced K+ release, which was in
      contrast with its inhibitory effect on amylase release. These results suggest
      that the K+ release from rat parotid acini induced by CCh stimulation is mediated
      by a rapid increase in [Ca2+]i but is not associated with activation of protein
      kinase C. This signal pathway is different from that for amylase release where
      activation of protein kinase C plays an important role.

PMID- 7509889
TI  - Protective effect of N-acyl amino acids (NAAs) on cephaloridine (CER)
      nephrotoxicity in rabbits.
AB  - The protective effect of N-acyl amino acids (NAAs) against cephaloridine (CER)
      induced nephrotoxicity was studied in rabbits. A large single intravenous dose of
      CER (more than 100 mg/kg) induced severe proximal tubular necrosis. Simultaneous
      treatment with several NAAs (at dosages of 100, 200 mg/kg, etc., i.v.), such as N
      benzoyl-beta-alanine (NBBA), N-benzoyl-6-aminocaproic acid, and N alpha,epsilon
      dibenzoyl-D,L-lysine, remarkably suppressed the histopathological damage in the
      kidney induced by CER. NAAs have generally low toxicity in laboratory animals
      (e.g., the LD50 of NBBA was more than 3,000 mg/kg, i.v. in rats), and NAAs were
      suggested to be good candidates for reducing the nephrotoxicity of CER and other
      beta-lactam antibiotics.

PMID- 7509892
TI  - [Selected cases of metastatic tumors to the visual system].
AB  - Metastases are always bad prognostic symptoms. They occur rather rarely, but may
      involve each element of visual system uni- or bilaterally. Usually we found these
      metastatic tumors in patients with earlier diagnosed neoplastic disease, in
      various tissues and organs. Therefore, in majority of cases treatment is only
      palliative, especially in those with the only eye or when the process is
      bilateral.

PMID- 7509890
TI  - [Lung residuals following chemotherapy in patients with stage III nonseminomatous
      testicular cancer. Report of 4 cases].
AB  - Since 1989, 4 patients with Stage III nonseminomatous germ cell tumor of the
      testis underwent thoracotomy for persistent radiographic masses after systemic
      chemotherapy. They were treated with multi-drug regimen including cisplatin,
      vincristine, methotrexate, peplomycin, and etoposide until normalization of tumor
      markers was obtained. Residual masses of the 4 patients consisted of viable
      cancer cells in 1 patient, immature teratoma in 1, mature teratoma in 1 and
      necrosis in 1. Of the 4 patients 3 achieved complete remission and are doing well
      with no evidence of disease, while the other case with residual viable cancer
      cells died of renal failure. The key to successful treatment of advanced
      testicular cancer was considered to be a favorable response to chemotherapy and
      complete resection of any residual tumors.

PMID- 7509891
TI  - [Autonomic regulation of cardiac activity and variability of heart rhythm in
      patients with frequent ventricular extrasystole].

PMID- 7509894
TI  - Bisoprolol and atenolol in essential hypertension: effects on systemic and renal
      hemodynamics and on ambulatory blood pressure.
AB  - The acute and short-term responses to bisoprolol and to atenolol on systemic and
      renal hemodynamics and on ambulatory blood pressure (BP) were compared in a
      randomized double-blind cross-over study including 14 patients with mild to
      moderate essential hypertension. After a 4-week placebo period, the patients
      received either bisoprolol (10 mg once daily, o.d.) or atenolol (100 mg o.d.) for
      4 weeks and were switched to the other drug after a new 4-week placebo period.
      Cardiac output (CO) was measured by Doppler echography, and renal blood flow
      (RBF) and glomerular filtration rate (GFR) were measured by constant infusion
      techniques using [123I]iodohippurate and [51Cr]EDTA, respectively. Bisoprolol and
      atenolol decreased diurnal and nocturnal blood pressure (BP). Both drugs
      decreased heart rate (HR) and BP both acutely and after 4 weeks. During short
      term treatment, CO was maintained with bisoprolol but reduced by atenolol (by
      17%). RBF decreased after the first drug intake (by 9 and 12%, respectively) but
      returned to its baseline value after 4 weeks, so that calculated renal vascular
      resistance (RVR) was reduced (by 12 and 15%, respectively). Overall, GFR was not
      affected by treatment. Bisoprolol and atenolol are effective antihypertensive
      agents that preserve renal hemodynamics during short-term treatment.

PMID- 7509893
TI  - Hemodynamics, tolerability, and pharmacokinetics of linsidomine (SIN-1) infusion
      during the acute phase of uncomplicated myocardial infarction.
AB  - To determine a dose regimen and evaluate the hemodynamic effects of linsidomine
      administered by continuous intravenous (i.v.) infusion, 10 patients were studied
      during the acute phase of uncomplicated myocardial infarction (MI). Systolic,
      diastolic, and mean (SBP, DBP, MBP) systemic blood pressure and heart rate (HR)
      were measured noninvasively. Pulmonary artery pressures were monitored after
      insertion of a Swan-Ganz catheter, which also enabled measurement of cardiac
      output (CO) and cardiac index (CI) by thermodilution. After baseline hemodynamic
      values (period A) were determined, linsidomine (SIN-1) was infused at a rate of
      0.8 mg/h and subsequently adjusted to obtain a 10% decrease in MBP from its
      baseline value (period B). The infusion was then continued for 3 h at a constant
      rate (period C), and pressures were monitored for 1 h after the infusion was
      discontinued (period D). There were no significant changes in systemic or
      pulmonary arterial pressures or in HR between period B and period C. In contrast,
      CI decreased moderately (p < 0.05), with no clinical consequences. Return to
      baseline hemodynamics was obtained at the end of period D. Our findings indicate
      that continuous i.v. administration of SIN-1 (at a mean flow rate of 1 mg/h) is
      well tolerated and appears to be suitable for use in acute coronary syndromes.

PMID- 7509895
TI  - Effects of a xanthine oxidase/hypoxanthine free radical and reactive oxygen
      species generating system on endothelial function in New Zealand white rabbit
      aortic rings.
AB  - We investigated the effects of the xanthine oxidase (XO)/hypoxanthine (HX) free
      radical (FR) generating system on the relaxant properties of aortic rings from
      New Zealand White rabbits. This system generates superoxide anions, hydroxyl
      radicals, and H2O2. We wished to identify which of these species is responsible
      for impairment of vascular function. After obtaining dose-response curves to
      phenylephrine (PE) and carbachol or sodium nitroprusside (SNP), we exposed rings
      to the FR generating system or H2O2 for 30 min, either with or without a range of
      potentially protective agents. Dose-response curves to carbachol or SNP were then
      repeated. Exposure to the XO/HX system impaired endothelium-dependent, carbachol
      induced relaxation. The hydroxyl radical scavengers mannitol, N-(2
      mercaptopropionyl)-glycine (MPG), and captopril offered no protection. Superoxide
      dismutase (SOD) increased the impairment of response, catalase provided partial
      protection, and a combination of SOD and catalase completely prevented impairment
      of the response. H2O2 mimicked the effects of XO/HX system. H2O2 appears to be
      the primary species involved in mediating the toxic effects of the XO/HX FR
      generating system, but the superoxide anion is probably responsible for some of
      the loss of relaxation and a role for intracellular generation of hydroxyl
      radicals cannot be excluded.

PMID- 7509896
TI  - Mechanisms of ventricular arrhythmia during amitriptyline toxicity.
AB  - The ventricular tachycardia (VT) caused by high-dose tricyclic antidepressants
      has been hypothesized to be due to a quinidinelike effect with generation of
      repolarization abnormalities and afterdepolarizations. To test this hypothesis
      further, we infused amitriptyline in a graded fashion (0.5-1 mg/kg/min) in 23
      chloralose-anesthetized dogs during endocardial monophasic action potential (AP)
      recording and continuous hemodynamic monitoring. Three groups of dogs were
      studied: group A (n = 5), crushed sinus node and fixed atrial pacing at 100
      beats/min; group B (n = 12), crushed sinus node and fixed atrial pace plus
      intermittent accelerated pacing to mimic group C; and group C (n = 6) intact
      sinus node and unimpeded sinus tachycardia. Amitriptyline infusion induced VT in
      no (0 of 5) group A dogs, all (12 of 12) group B dogs during accelerated pacing,
      and 83% (5 of 6) of group C dogs. Dogs with VT had significantly higher heart
      rates (HR 184.8 +/- 39.3 beats/min) as compared with dogs without VT (115.2 +/-
      12.5 beats/min, p = 0.0015). There was a strong positive correlation between the
      last RR coupling interval to the first VT interval (r = 0.85; p = 0.0033).
      Amitriptyline infusion caused rate-dependent QRS prolongation in each group,
      especially group C (p < 0.001). Action potential duration at 50% and 90% of
      repolarization (APD50, APD90) showed a biphasic response with progressive
      shortening followed by prolongation as amitriptyline serum concentrations
      increased. Afterdepolarizations were not detected from any monophasic AP
      recording, even in dogs with VT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509897
TI  - Pharmacologic properties of a novel Ca2+ entry blocker, AJ-2615, in vitro.
AB  - We studied the in vitro vascular relaxant properties of AJ-2615, (+/-)-N-[6,11
      dihydrodibenzo[b,e]-thiepin-11-yl]-4-[4- fluorophenyl]-1-piperazinebutanamide
      monomaleate, a novel compound with long-lasting antihypertensive activity. AJ
      2615 inhibited the high K(+)-induced contractile response in rat aorta with an
      IC50 of 2.08 x 10(-8) M. It was 13 times less potent than nifedipine and 3, 10,
      and 15 times more potent than verapamil, diltiazem, and fluanarizine,
      respectively. AJ-2615 also inhibited the high K(+)-induced 45Ca influx in rat
      aorta at almost the same concentration as that for inhibition of the contractile
      response. The inhibition of 45Ca influx was reversed by Bay k 8644, a Ca2+
      channel agonist. The effects of AJ-2615 on the contractile response and Ca2+
      influx persisted for at least 120 min after AJ-2615 was removed from the medium.
      These results indicate that AJ-2615 acts directly on the potential-dependent Ca2+
      channel in a long-lasting manner. AJ-2615 inhibited [3H]prazosin binding to dog
      aortic membranes (IC50 = 1.25 x 10(-8) M) and phenylephrine-induced contractile
      response in superior mesenteric artery (SMA) of rabbits (IC50 = 3.87 x 10(-8) M),
      indicating that AJ-2615 has potent alpha 1-adrenoceptor blocking activity. AJ
      2615 at 10(-6) M did not inhibit the caffeine-induced contractile response in
      rabbit SMA in Ca(2+)-free medium, nor did it inhibit calmodulin (CAM)
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509898
TI  - Protection against programmed electrical stimulation-induced ventricular
      tachycardia and sudden cardiac death by NE-10064, a class III antiarrhythmic
      drug.
AB  - The electrophysiologic and antifibrillatory properties of NE-10064 were studied
      in vivo in a conscious canine model of sudden cardiac death. Purpose bred male
      mongrel dogs weighing 14.5-21.5 kg were anesthetized, and surgical anterior
      myocardial infarction (MI) was induced by a 2-h occlusion, with reperfusion, of
      the left anterior descending coronary artery (LAD). Three to 5 days after
      induction of anterior wall MI, animals were subjected to testing by programmed
      electrical stimulation (PES). As compared with predrug incidence (12 of 12), NE
      10064 (10 mg/kg intravenously, i.v.) reduced (p < 0.05) the incidence (8 of 12)
      of PES-induced ventricular tachycardia (VT). All but 1 control animal remained
      inducible after vehicle (5% dextrose in water). The cycle length of induced VT
      was not prolonged by NE-10064 (0.245 +/- 0.046 s predrug vs. 0.301 +/- 0.060 s
      postdrug). NE-10064 increased ventricular effective refractory period (VERP 166
      +/- 5 ms predrug vs. 194 +/- 13 ms postdrug, p = 0.013), prolonged QTc interval
      (310 +/- 12 ms predrug vs. 350 +/- 16 ms postdrug, p = 0.004) and prolonged the
      effective refractory period (ERP) of noninfarcted myocardium (p = 0.045). The
      drug did not affect ECG-indexes of conduction velocity: QRS and P-R intervals
      were not affected, nor were activation delay and conduction time of noninfarcted
      and infarcted myocardium. In the sudden cardiac death protocol, NE-10064
      protected (p = 0.018) against ischemia-induced ventricular fibrillation (VF, 75%
      survival with drug vs. 25% survival without drug). NE-10064 afforded protection
      (p = 0.040) throughout 14 h posterolateral ischemia in the presence of the
      previous anterior infarct.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509899
TI  - Acute and prolonged hypoxia attenuate endothelial nitric oxide production in rat
      pulmonary arteries by different mechanisms.
AB  - Hypoxic pulmonary hypertension complicates many primary respiratory and cardiac
      conditions. To define the potential role of endothelial nitric oxide (NO) further
      in both the acute and chronic forms of this disorder, we determined the effects
      of acute changes in O2 in vitro and prolonged variations in O2 in vivo on
      endothelial NO production in rat main pulmonary arteries. NO production was
      assessed by measuring segment cyclic GMP synthesis, which was dependent on the
      presence of the endothelium and on NO synthase and soluble guanylate cyclase
      activity. With an acute decrease in pO2 in vitro from 150 to 40 mm Hg, basal
      endothelial NO production was attenuated by 52%. NO production stimulated by
      acetylcholine (ACh) or A23187, however, was not altered, suggesting that the
      underlying mechanism involves acute changes in endothelial intracellular calcium
      homeostasis or in the production or action of a local activator of endothelial NO
      synthase. Although prolonged hypoxia in vivo (7 days) also caused a 52% decrease
      in basal endothelial NO production, ACh- and A23187-stimulated production were
      diminished as well, by 69 and 73%, respectively; the attenuation in NO production
      was evident when tested at high pO2 in vitro, was not altered by exogenous L
      arginine, and was reversed by 3 days of normoxic recovery, indicating that the
      chronic process may involve diminished availability of cofactor(s) required for
      NO synthase activity. Parallel studies of aortic segments showed that these
      effects are specific to the pulmonary endothelium. Thus, both acute and prolonged
      hypoxia selectively attenuate pulmonary endothelial NO production by different
      mechanisms.

PMID- 7509900
TI  - Trimetazidine inhibits neutrophil accumulation after myocardial ischaemia and
      reperfusion in rabbits.
AB  - Interventions that inhibit neutrophil infiltration into myocardial tissue after
      ischaemia and reperfusion are reported to reduce the size of the infarct. We
      examined whether administration of trimetazidine, which is reported to reduce
      myocardial infarct size, affects this process. [111In]Neutrophils and
      [125I]albumin were administered intravenously (i.v.) to anaesthetized rabbits to
      allow measurement of cell accumulation and changes in microvascular plasma
      protein leakage. A 30-min period of coronary artery occlusion followed by 3-h
      reperfusion was used, and the area at risk (AR) myocardium was defined by dye
      exclusion. Twelve rabbits received 2.5 mg/kg trimetazidine i.v., 10 min before
      coronary artery occlusion; the 13 controls received saline. In the control group,
      the number of [111In]neutrophils/g tissue in the AR (30,591 +/- 6,725) was
      significantly greater than in the normal zone (NZ, 11,519 +/- 1,605, p < 0.01).
      In the trimetazidine-treated group, the number of [111In]neutrophils in the AR
      was significantly lower than in the control group (12,717 +/- 1,958
      [111In]neutrophils/g, p < 0.01). There was no significant difference in
      neutrophil content of the NZ (7,832 +/- 1,117 [111In]neutrophils/g) in treated
      animals as compared with that in control. Accumulation of [111In]neutrophils in
      response to intradermal administration of leukotriene B4, interleukin-8 (IL-8),
      or zymosan-activated plasma was not affected by the drug. The effect of
      trimetazidine on neutrophil accumulation into post-ischaemic reperfused
      myocardium therefore does not appear to result from a direct action on the
      neutrophil.

PMID- 7509901
TI  - Intracoronary infusion of E6010 has more potent thrombolytic activity than tissue
      plasminogen activator (t-PA) in dogs: a higher plasma level of E6010 than t-PA
      causes potent thrombolytic activity.
AB  - We examined the thrombolytic properties of a novel modified human tissue
      plasminogen activator (PA) (E6010), in which cysteine 84 is replaced by serine,
      and which has a prolonged biologic half-life (t1/2). We compared the thrombolytic
      efficacy of continuous intracoronary (i.c.) infusion of E6010 with that of
      recombinant human tissue PA (rt-PA) in a canine model with copper coil-induced 1
      h-old coronary artery thrombi and also compared the relation between thrombolytic
      efficacy and plasma clearance represented by pharmacokinetic parameters of i.c.
      infused E6010 and rt-PA. Sixty-minute E6010 and rt-PA i.c. infusions were
      compared. The thrombolytic effects of i.c.-infused E6010 and rt-PA, represented
      by time to reperfusion (TR), reperfusion rate at 60 min (RR), and reocclusion
      rates at 60 min after reperfusion (OR) were as follows. E6010: Dose 0.06, 0.15,
      0.3 (mg/kg/h); TR 25 +/- 10, 15 +/- 10, 13 +/- 5 (min); RR 100, 100, 100 (%); and
      OR 0, 0, 17 (%), respectively. Recombinant t-PA: Dose 0.06, 0.15, 0.3 (mg/kg/h);
      TR 47 +/- 12, 18 +/- 17, 14 +/- 4 (min); RR 50, 75, 100 (%); and OR 100, 33, 33
      (%), respectively. These findings indicate that E6010 has more potent
      thrombolytic activity than rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509902
TI  - Muscarinic receptor subtypes mediating vasodilation and vasoconstriction in
      isolated, perfused simian coronary arteries.
AB  - Using the cannula insertion method, we investigated the vascular responses of
      isolated simian coronary artery to acetylcholine (ACh). When the preparation was
      partially precontracted by 20 mM KCl, ACh and carbachol induced vasodilation dose
      dependently in coronary artery with endothelium, but ACh and carbachol contracted
      the coronary artery after removal of the endothelium by 1 mg saponin. A selective
      M1 receptor agonist 4-[N-(3-chlorophenyl)carbamoyloxy]-2
      butinyltrimethylammonium++ + chloride (McN-A-343) did not affect the perfusion
      pressure of the precontracted coronary arteries significantly. Both these
      responses to ACh were inhibited by the M3 receptor antagonist 4-dipheny-lacetoxy
      N-methylpiperidine methobromide (4-DAMP) in a dose-dependent manner, but not by a
      selective M2 receptor antagonist AF-DX 116 (11-[[2-[(diethylamino)methyl]-1
      piperidinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzo-diazepine-6-one). A
      selective M1 receptor antagonist pirenzepine did not affect ACh-induced
      vasoconstriction significantly and inhibited the vasodilation partially only at
      the highest dose (100 nmol). The effects of three antagonists on the vasodilative
      responses to carbachol were also studied and almost the same results were
      observed. Removal of the endothelium did not affect sodium nitroprusside (SNP)
      induced vasodilation significantly. Pirenzepine, AF-DX 116, and 4-DAMP did not
      affect the action of isoproterenol. These data suggest that the vasodilation
      elicited by ACh is mediated by release of endothelium-derived relaxing factors
      (EDRF) consequent to the activation of M3 receptors on endothelial cells, and the
      constriction is mediated by stimulation of M3 receptors on smooth muscle cells in
      isolated simian coronary arteries.

PMID- 7509905
TI  - Reperfusion-induced accumulation of long-chain acylcarnitines in previously
      ischemic myocardium.
AB  - Long-chain acylcarnitines (LCA) have been shown to accumulate during myocardial
      ischemia and to contribute to malignant derangements characteristic of ischemia.
      We detail the time course of the increase in LCA levels during both ischemia and
      reperfusion. Evidence indicates an additional specific reperfusion-induced
      increase in LCA that peaks at 2 min and decreases to basal levels by 30 min. This
      increase in LCA during reperfusion is observed after 2-, 10-, or 20-min ischemia
      and is inhibited by the presence of the carnitine palmitoyl transferase 1 (CPT1)
      inhibitor phenyloxirane carboxylic acid (POCA). A role for increased LCA in
      mediating "reperfusion damage" is not indicated, however, because POCA did not
      attenuate either the incidence of ventricular fibrillation (VF) during early
      reperfusion or the survival rate of rats undergoing 24-h reperfusion after 10-min
      occlusion.

PMID- 7509903
TI  - Effects of a new forskolin derivative, NKH477, on canine ventricular arrhythmia
      models.
AB  - Using two-stage coronary ligation-, digitalis- and epinephrine-induced canine
      ventricular arrhythmia models, we examined whether a new positive inotropic
      agent, NKH477, 6-(3-dimethylaminopropionyl)forskolin hydrochloride, a water
      soluble derivative of forskolin, had deleterious effects on arrhythmias. NKH477
      increased heart rate (HR) and decreased blood pressure (BP) in dogs with all the
      arrhythmia models. Unexpectedly, NKH477 suppressed digitalis- and epinephrine
      induced arrhythmias, but did not suppress two-stage coronary ligation arrhythmia
      or aggravate it. These results indicate that NKH477, unlike other new positive
      inotropic agents such as amrinone, milrinone, sulmazole and vesnarinone, did not
      worsen these arrhythmias; thus, NKH477 may be a useful positive inotropic agent
      with little arrhythmogenic effect.

PMID- 7509904
TI  - Influences of pravastatin and simvastatin, HMG-CoA reductase inhibitors, on
      myocardial stunning in dogs.
AB  - We examined the effects of pravastatin and simvastatin, HMG-CoA reductase
      inhibitors, on stunned myocardium in vivo. Pravastatin and simvastatin were given
      orally 2 mg/kg for 3 weeks. After 3 weeks of administration, pentobarbital
      anesthetized dogs were subjected to 15-min left anterior descending (LAD)
      coronary artery occlusion followed by 2-h reperfusion. Myocardial segment
      function was determined by sonomicrometry. The tissue energy and carbohydrate
      metabolites were determined in the 2-h-reperfused hearts. Administration of
      pravastatin and simvastatin for 3 weeks decreased serum cholesterol level and
      blood pressure (BP). Simvastatin resulted in a worsening of segment shortening in
      the reperfused myocardium as compared with control and pravastatin groups. The
      level of ATP in the simvastatin group was significantly lower as compared with
      that in the control group. The other metabolite levels were not significantly
      altered by either pravastatin or simvastatin. These results suggest that
      simvastatin enhances stunning of the myocardium in association with ATP reduction
      after reperfusion subsequent to ischemia.

PMID- 7509906
TI  - Effects of ATP-sensitive K+ channel openers on pacemaker activity in isolated
      single rabbit sino-atrial node cells.
AB  - Electrophysiologic effects of ATP-sensitive K+ channel openers (cromakalim,
      pinacidil, and nicorandil) in single rabbit sino-atrial (SA) node cells were
      examined by a whole-cell voltage- and current-clamp technique. Cromakalim (> 30
      microM), pinacidil (> 1 microM), and nicorandil (> 500 microM) caused a negative
      chronotropic effect. At low concentrations, the maximum diastolic potential was
      hyperpolarized and the maximum rate of depolarization was enhanced, but at high
      concentrations, both were reversed and action potential amplitude (APA) was
      decreased significantly. Pinacidil (> 30 microM) and nicorandil (> 3 microM)
      prolonged AP duration (APD), but cromakalim did not affect it. In whole-cell
      voltage-clamp experiments, cromakalim (100 microM), pinacidil (> 30 microM), and
      nicorandil (> 300 microM) inhibited the Ca2+ current significantly but had little
      or no effect on the delayed rectifying K+ current and the hyperpolarization
      activated inward current. Glibenclamide (1 microM) did not antagonize the effects
      of K+ channel openers on Ca2+ current and APs. These results indicate that the K+
      channel openers have direct inhibitory actions on spontaneous APs and Ca2+
      current in rabbit SA node cells (but K+ current was unaffected), resulting in
      decreased pacemaker activity.

PMID- 7509907
TI  - Effects of cocaine on cardiac vagal tone before and during coronary artery
      occlusion: cocaine exacerbates the autonomic response to myocardial ischemia.
AB  - Cocaine is a potent sympathomimetic drug that can provoke lethal cardiac events.
      Cocaine-induced alterations in autonomic balance, particularly during myocardial
      ischemia, could contribute significantly to these adverse reactions. To test this
      hypothesis, we produced a 2-min left circumflex coronary artery (LCX) occlusion
      in unanesthetized mongrel dogs (n = 7) instrumented to measure left ventricular
      pressure (LVP), ventricular electrogram, and coronary blood flow (CBF) with and
      without various doses of cocaine (0.0, 0.5, 1, 2, and 4 mg/kg). At least 24 h
      elapsed between cocaine doses, which were given in random order. Time series
      analysis of heart rate (HR) variability was used as an index of cardiac vagal
      tone (0.24-1.04 Hz). Cocaine elicited dose-dependent increases in HR that were
      accompanied by corresponding decreases in cardiac vagal tone. The peak response
      was achieved approximately 1 min after cocaine was given and returned to
      precocaine values 15 (0.5 and 1 mg/kg), 30 (2 mg/kg), or 60 (4 mg/kg) min later.
      Myocardial ischemia elicited significant increases in HR and reductions in
      cardiac vagal tone that were accentuated by cocaine (1, 2, and 4 mg/kg); e.g.,
      cocaine (2 mg/kg) elicited a greater HR (control 119.3 +/- 5.9, occlusion 149.7
      +/- 9.6; cocaine 144 +/- 11.9, occlusion 178.3 +/- 10.4 beats/min) and vagal tone
      (control 5.6 +/- 0.7, occlusion 2.6 +/- 0.3; cocaine 5.2 +/- 0.7, occlusion 1.3
      +/- 0.5 ln s2) response to 2-min coronary occlusion. beta-Adrenoceptor blockade
      (propranolol HCl 1 mg/kg) attenuated the HR response but elicited greater
      reduction (lower values were achieved) in vagal tone during coronary artery
      occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509908
TI  - Role for the Na+/H+ exchanger in reperfusion stunning in isolated perfused rat
      heart.
AB  - We tested the hypothesis that Na+/H+ exchange contributes to reperfusion stunning
      and arrhythmias. The effects of amiloride, an established inhibitor of Na+/H+
      exchange, were compared with those of a new inhibitor (HOE 694). Working hearts,
      subjected to 20-min global ischemia and reperfused for 30 min, were pretreated
      (for 5 min before ischemia) or reperfused (initial 2 min) with HOE 694 or
      amiloride. Pretreatment with 10(-7) M HOE increased recovery of aortic output
      (AO) after 30-min reperfusion: As a percentage of the preischemic controls,
      values were 38.5 +/- 3.6% (n = 7) for controls versus 50.6 +/- 3.9% (n = 5) for
      the treated group (p < 0.05). Pretreatment with HOE (10(-6) M) increased AO
      recoveries from 38.2 +/- 2.0% (n = 5) to 52.9 +/- 2.7% (n = 5) (p < 0.05).
      Amiloride (10(-5) M) pretreatment improved AO recoveries from 41.6 +/- 2.7% (n =
      6) to 55.8 +/- 4.0% (n = 6) (p < 0.05). Thus, pretreatment by both HOE 694 and
      amiloride decreased reperfusion stunning. Adding HOE (10(-7) M) only in the
      reperfusion period increased AO recoveries from 36.4 +/- 1.2% (n = 6) to 62.4 +/-
      3.2% (n = 11) (p < 0.002). Amiloride (10(-5) or 10(-3) M) added only during
      reperfusion did not improve recovery of AO. HOE 694, active in much lower
      concentrations than amiloride, was the only compound active against stunning when
      added only during reperfusion. In addition, both compounds inhibited reperfusion
      arrhythmias when added at reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509909
TI  - NG-monomethyl-L-ARG reduces the forearm vasodilator response to acetylcholine but
      not to methacholine in humans.
AB  - We compared the contribution of nitric oxide (NO) in methacholine (MCh)- and
      acetylcholine (ACh)-induced vasodilation using the NO-synthase inhibitor NG
      monomethyl-L-arginine acetate (L-NMMA-acetate) in two groups (A and B) of 6
      healthy male volunteers. The left brachial artery was cannulated for drug
      infusion and recording of mean arterial pressure (MAP). Forearm blood flow (FBF)
      was measured on both sides by venous occlusion mercury-in-silastic strain-gauge
      plethysmography. All measurements were performed with occluded hand circulation.
      Forearm vasodilator response to three increasing dosages of MCh (0.03, 0.3, and 1
      micrograms/100 ml forearm/min; group A) or ACh (0.5, 2, and 8 micrograms/100 ml
      forearm/min; group B) was studied first. Forty-five minutes later, these
      infusions were repeated (after and during local administration of L-NMMA). L-NMMA
      acetate infusion alone increased basal forearm vascular resistance (FVR, mean +/-
      SE) by 86.2 +/- 14.5 and 99.5 +/- 27.4% in groups A and B, respectively (p <
      0.05) without significant FVR changes in the control arm. MCh-induced
      vasodilation was not attenuated by concomitant L-NMMA-acetate infusion. In
      contrast, L-NMMA-acetate significantly reduced the averaged percentage decrease
      in FVR during infusion of ACh from 55.7 +/- 9.1 to 35.4 +/- 11.8% (p < 0.05). L
      NMMA-acetate increased basal vascular tone and reduced the vasodilator response
      to ACh. MCh induced vasodilation to a degree similar to that obtained with ACh.
      Nevertheless, MCh-induced vasodilation could not be attenuated by L-NMMA,
      suggesting that NO contributes differentially to methacholine- and ACh-induced
      vasodilation in humans.

PMID- 7509911
TI  - Telemetric monitoring of cardiovascular parameters in conscious spontaneously
      hypertensive rats.
AB  - We compared cardiovascular values obtained with a telemetric system
      simultaneously with those recorded by an externalized catheter in spontaneously
      hypertensive rats (SHR). We also tested the hypothesis that telemetric monitoring
      reduces the amount of stress associated with performance of cardiovascular
      studies. Femoral arterial and venous catheters were implanted under
      methoxyflurane anesthesia in male SHR previously implanted 38 +/- 7 days earlier
      with radiotelemetric devices. Rats were then allowed 1 day to recover before
      undergoing experimentation. Baseline blood pressure (BP) and heart rate (HR)
      values obtained with the telemetric system and with the femoral arterial
      catheters were similar, and intravenous (i.v.) administration of phenylephrine
      (PE), angiotensin I (ANGI), acetylcholine (ACh), or nitroglycerin (NTG) evoked
      similar changes in BP and HR. Hemodynamic responses evoked by i.v. administration
      of nifedipine were also similar as recorded by telemetric monitoring and the
      femoral arterial cannula. Baseline cardiovascular parameters measured in SHR
      instrumented only with telemetric devices consistently yielded BP and HR values
      significantly lower than those recorded by tail-cuff or femoral catheters. In
      addition, SHR subjected to the tail-cuff procedure responded to oral
      administration of captopril with a greater degree of hypotension. These studies
      demonstrate that telemetric monitoring of cardiovascular parameters in conscious
      rats is a sensitive, accurate, and flexible method. The lower basal
      cardiovascular values and the insensitivity to the hypotensive effects of
      angiotensin-converting enzyme (ACE) inhibition, suggest that a decreased level of
      stress is associated with performance of cardiovascular studies by a
      radiotelemetric system.

PMID- 7509910
TI  - Loss of endothelium-dependent relaxation in proximal pulmonary arteries from rats
      exposed to chronic hypoxia: effects of in vivo and in vitro supplementation with
      L-arginine.
AB  - To explore endothelium-dependent relaxation and the L-arginine (L-ARG)-nitric
      oxide (NO) pathway during chronic hypoxia, we examined isolated rings from large
      conduit pulmonary arteries and aorta from rats exposed to either room air (N), 3
      week hypoxia (H), or 3-week H followed by 72-h recovery to normoxia (room air).
      We examined the vasodilatory actions of acetylcholine (ACh), ionophore A23187,
      and endothelin-3 (ET-3) on extrapulmonary left and right branches of pulmonary
      arteries and thoracic aorta precontracted by phenylephrine (PE 10(-6) M).
      Endothelium-dependent relaxation of N rat pulmonary arteries and aorta to ACh and
      A23187 was abolished in the presence of L-NG nitroarginine methyl ester (L-NAME
      10(-4) M) or methylene blue (MB 10(-5) M) but was suppressed only partially by NG
      monomethyl-L-arginine (L-NMMA 5 x 10(-4) M). In pulmonary arteries but not in
      aorta, ET-3 induced endothelium-dependent relaxation that was suppressed by L
      NAME, MB, and L-NMMA. Pulmonary arteries from H rats did not relax with ET-3. As
      compared with those of N rats, they exhibited less relaxation to ACh and A23187,
      (47 +/- 3 vs. 89 +/- 2 and 53 +/- 2 vs. 85 +/- 4%, p < 0.001, respectively) but
      exhibited similar relaxation to the nonendothelium-dependent vasodilator
      linsidomine. In contrast, endothelial-relaxation did not differ between N and H
      rat aorta.2+ pretreatment with L-ARG.

PMID- 7509912
TI  - Nomenclature of calcium channels and channel modulators: IUPHAR classification.

PMID- 7509914
TI  - Proceedings of the 3rd International Conference on Endothelin. Houston, Texas,
      February 15-17, 1993.

PMID- 7509913
TI  - Endothelin receptor B expression in the rat and rabbit lung as determined by in
      situ hybridization using nonisotopic probes.
AB  - Endothelins are a family of potent vasoactive peptides. Full-length cDNA clones
      to human endothelin receptor B (ETB) mRNA were random prime-labeled with
      nucleotides conjugated to digoxigenin for in situ hybridization. The labeled cDNA
      was used to probe frozen sections of rat and rabbit lung. Detection of the
      digoxigenin-labeled probe was accomplished by an antibody-enzyme conjugate, anti
      digoxigenin alkaline phosphatase. The location of the antibody-antigen complex
      was visualized as an enzyme-linked color reaction. The hybridization, washings,
      and detection steps were performed under stringent conditions. The following cell
      types of the rat and rabbit lung had abundant positive reaction product to the
      ETB probe: bronchiolar and bronchial epithelium, endothelium of smooth-muscle-
      walled vessels, and bronchial and bronchiolar-associated lymphoid tissue.
      Abundant positive reaction product was also observed in cell populations in the
      lung parenchyma. Additional studies are being performed to identify those
      populations. The results of this study suggest that in addition to vasoactivity,
      endothelins play other important roles in the lung.

PMID- 7509915
TI  - Vasoconstriction in the rat kidney induced by endothelin-1 is blocked by PD
      145065.
AB  - We have previously shown that the receptors mediating the renal and systemic
      vasoconstrictor effects of endothelin-1 (ET-1) are of two distinct endothelin
      receptor subtypes. Here, we evaluate the effect of PD 145065, a nonselective
      endothelin receptor antagonist, on the renal vasoconstrictor effects of ET-1 in
      the rat kidney. ET-1 induced concentration-dependent increases in perfusion
      pressure in the isolated perfused kidney of the rat. The ETA receptor-selective
      antagonists BQ-123 (10 microM) and FR 139317 (10 microM) lowered the ET-1-induced
      rise in perfusion pressure by 57% and 61%, respectively, at 3 x 10(-10) M ET-1.
      By comparison, the ET-1-induced vasoconstriction was fully antagonized (96%
      inhibition) by PD 145065 (10 microM). In the anesthetized rat, ET-1 produced a
      dose-dependent increase in mean arterial pressure, which was attenuated by PD
      145065. The initial depressor response to ET-1 was completely blocked by PD
      145065, as were the reduction in renal blood flow and increase in renal vascular
      resistance induced by ET-1. These results suggest that both the ETA and a non-ETA
      receptor subtype play an important role in mediating the vasoconstrictor effects
      of ET-1 in the rat kidney.

PMID- 7509917
TI  - Desensitization of human endothelin A receptor.
AB  - The response of G-protein-coupled receptors is modulated by homologous
      desensitization. Because endothelin A receptor (ETA) plays a part in
      vasoconstriction, the extent of desensitization and resensitization of endothelin
      responsiveness was studied. A cDNA clone encoding human ETA receptor was isolated
      based on similarities to bovine endothelin A receptor. Xenopus laevis oocytes
      injected with cloned mRNA transcripts were used as a model system for analyzing
      desensitization. Human neurokinin A (NKA) receptor was used for comparison with
      ETA receptor in desensitization experiments. Xenopus laevis oocytes injected with
      the two receptor mRNAs show homologous desensitization but variable rates of
      recovery. Human NKA receptors desensitize within 5 min and resensitize after 20
      30 min. Human ETA receptors also desensitize within 5 min but have a prolonged
      resensitization period lasting 1.5-2 h. Such a prolonged recovery period is
      unique to this class of receptors and may serve to regulate some of the
      deleterious effects mediated by the ETA receptor. The mechanism of differential
      desensitization is being investigated using genetically engineered mutants of
      human ETA receptor.

PMID- 7509916
TI  - Pharmacologic profile of endothelinA/B antagonist, [Thr18, gamma methyl
      Leu19]endothelin-1.
AB  - The pharmacologic profile of [Thr18,gamma methyl Leu19]endothelin-1 (TM ET-1) was
      investigated in several in vitro and in vivo studies. We found that TM ET-1
      inhibited 125I-ET-1 binding in porcine cardiac membrane (ETA receptor) and in
      bovine brain membrane (ETB receptor), with IC50 values of 0.7 and 0.25 nM,
      respectively. These values were almost comparable to those for ET-1. TM ET-1 had
      no effect on intracellular Ca2+ concentration ([Ca]i) in A10 cells mediated by
      ETA receptors, even at 10(-5) M, or in mouse peritoneal macrophages (MPMs)
      mediated by ETB receptors, even at 10(-6) M. Increases in [CA]i in A10 cells by
      ET-1 and in MPMs by ET-3 were completely blocked by pretreatment with 10(-7) M of
      TM ET-1. In porcine right coronary arteries (PCAs) and in great cardiac veins
      (PCVs), TM ET-1 caused no contraction at concentrations < or = 10(-6) and 10(-7)
      M, respectively, although it competitively inhibited ET-1-induced contraction of
      PCAs and Ala1,3,11,15-ET-1-induced constriction of PCVs with pA2 values of 7.0
      and 9.2, respectively. Furthermore, TM ET-1 was more potent than BQ123, an ETA
      specific antagonist, in inhibiting the rise in perfusion pressure in a hind-limb
      preparation in vitro and the increase in blood pressure in rats. These results
      suggest that TM ET-1 is a potent ETA and ETB antagonist without agonistic effects
      and can be used in future studies to help clarify the physiological role of ET.

PMID- 7509918
TI  - Endothelium localization of ETB receptor revealed by immunohistochemistry.
AB  - The ETB receptor has been found to be predominantly expressed in the vascular
      endothelium of various bovine tissues by immunostaining with a highly specific
      antiserum that does not cross-react with ETA. The tissues examined include the
      lung, trachea, kidney, adrenal gland, pituitary gland, and cerebellum. The wide
      spread localization of ETB in the endothelial lining suggests that there is an
      ETB-mediated autocrine system of endothelin, which plays an important role in
      regulation of the functions of endothelial cells.

PMID- 7509919
TI  - The ligand-receptor interactions of the endothelin systems are mediated by
      distinct "message" and "address" domains.
AB  - Pharmacologic responses to endothelins (ETs) are mediated by two subtypes of G
      protein-coupled receptors, termed ETA and ETB. A chimeric receptor that has the
      transmembrane domains (TMDs) IV-VI with the adjacent loop regions from ETB
      embedded in the remaining regions from ETA exhibits specific binding to the N
      terminally truncated ETB agonists 125I-BQ3020 and 125I-IRL1620, to the same level
      as that of wild-type ETB receptor. Furthermore, the ETA-selective antagonist
      BQ123 competed for the binding of these ETB-selective radioligands to this
      chimeric receptor, with Ki values similar to those determined by using wild-type
      ETA receptor and 125I-ET-1. These findings indicated that the endothelin systems
      consist of two distinct parts, both on the ligand and receptor sides. The N
      terminal loop structure of the agonists and the TMDs IV-VI with adjoining loops
      of the receptors determine the isopeptide/subtype selectivity. On the other hand,
      the C-terminal linear portion of the isopeptides and the TMDs I-III and VII plus
      adjacent loops of the receptors are probably involved in ligand-receptor binding
      itself. This scheme can be explained by the classic "message-address" concept
      proposed for a number of peptidergic ligand families.

PMID- 7509920
TI  - Comparative studies with the endothelin receptor antagonists BQ-123 and PD 142893
      indicate at least three endothelin receptors.
AB  - Endothelin-1 (ET-1), endothelin-3 (ET-3), sarafotoxin 6b (SX6b), and sarafotoxin
      6C (SX6c) were used as agonists, and BQ-123 (ETA-selective) and PD 142893 (ET
      receptor-nonselective) were used as antagonists to characterize the receptors
      mediating the effects of the ET/SX peptides on a variety of isolated smooth
      muscle preparations. Contractions of the rat thoracic aorta, rat isolated
      perfused mesentery, and guinea pig ileum and potentiation of twitch of the rat
      vas deferens were mediated by ETA receptors in that they showed the order of
      potency ET-1 = SX6b > ET-3 >> SX6C. These effects were antagonized by BQ-123 or
      PD 142893. Contractions of the rabbit pulmonary artery and rat stomach strip,
      inhibition of twitches in the guinea pig ileum, and vasodilatations of the rat
      isolated perfused mesentery showed the order of potency ET-1 = SX6b = ET-3 = SX6c
      and were unaffected by BQ-123, suggesting involvement of ETB receptors. However,
      in these tissues, PD 142893 antagonized only dilatations of the rat mesentery to
      ET-1 but not any of the other effects of ET-1. Thus, we suggest that there are
      three types of endothelin receptors: ETA and two subtypes of ETB.

PMID- 7509922
TI  - Growth factor-induced modulation of endothelin-1 binding to human smooth-muscle
      cells.
AB  - Endothelin-1 (ET-1) has been shown to cooperate with other growth factors to
      enhance mitogenesis of fibroblasts and vascular smooth-muscle cells (SMCs) in
      vitro. One possible mechanism underlying such enhancement is the comodulation of
      receptor density/affinity for one factor by the other. In previous work, we
      showed that pretreatment of Swiss 3T3 fibroblasts with such growth factors as
      epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or basic
      fibroblast growth factor (bFGF) resulted in increased binding of 125I-ET-1 to
      these cells by two-, four-, and fivefold, respectively. To determine whether
      similar effects occur in human cells, 125I-ET-1 binding to early-passage human
      aortic SMCs was examined in untreated cells and in cells pretreated for 16 h with
      1.0 nM of EGF, PDGF, or bFGF. In untreated cells, Scatchard analysis confirmed
      26,500 +/- 2,000 (n = 4) binding sites with an apparent Kd of 105 +/- 53 pM.
      Pretreatment with EGF increased the number of binding sites to 36,500 +/- 4,950
      (n = 3) with no significant change in Kd (128 +/- 38 pM). Similarly, pretreatment
      with 1.0 nM bFGF also increased the number of 125I-ET-1 binding sites to 34,000
      +/- 1,700 (n = 3) with no significant change in Kd (94 +/- 13 pM). Unlike EGF and
      bFGF, pretreatment with PDGF-BB resulted in a decrease of 125I-ET-1 binding sites
      (14,600 +/- 2,300 sites/cell; n = 3) with no significant change in Kd (95 +/- 23
      pM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509921
TI  - Functional domains of human endothelin receptor.
AB  - The ligand binding site to the ETA receptor was investigated by substitution of
      each 5-amino acid sequence located in the second extracellular (B) region of the
      ETA receptor with the cognate sequences of the beta 2-adrenergic receptor. A 5
      amino acid sequence (140-KLLAG-144) in the B-loop region was implicated as the
      most important element required for ligand binding. In addition, both the third
      and the fourth extracellular regions (C- and D-loops), including the flanking
      transmembrane regions, were found to play an important role in ligand selection.
      As for the biological significance of the intracellular regions of the ETA
      receptor, we have found that the C-terminal 8-amino acid residues located in
      close proximity to the seventh transmembrane region and the C-terminal 16-amino
      acid residues in the third intracellular loop are important for the binding of ET
      1. Therefore, the intracellular third loop and C-terminal domains seem to
      contribute to the three-dimensional structure of the ligand binding site located
      in the extracellular domains. The same lines of experiment showed that the ETA
      receptor requires > 13 amino acid residues at the proximal cytoplasmic tail and
      10 amino acid residues in the C-terminal region of the third intracellular loop
      to induce an ET-1-dependent increase in [Ca2+]i. Both regions are possibly
      involved in the interaction with G-protein.

PMID- 7509925
TI  - Human placental membranes contain predominantly ETB receptors.
AB  - The endothelin (ET) receptors on human placental membranes (HPMs), coupled to
      fluomicrospheres, have been characterized by examining the binding of 125I-ET-1
      in a scintillation proximity assay (SPA). Specific binding of 125I-ET-1 was
      potently inhibited by ET-1 (IC50: 80 pM), ET-3 (IC50: 170 pM), and the ETB
      receptor-selective agonists sarafotoxin S6c (S6c; IC50: 210 pM) and
      alanine1,3,11,15-ET-1 (4-Ala-ET-1; IC50: 3.56 nM). In contrast, the ETA receptor
      selective antagonist BQ123 (D-Val-Leu-D-Trp-D-Asp-Pro) only weakly (28% at 10
      microM) inhibited 125I-ET-1 binding. In addition, the inhibition curves for ET-3
      and 4-Ala-ET-1 were shallow, with slopes less than unity, indicating binding-site
      heterogeneity. In keeping with this finding, the presence of a small population
      of ETA receptors was confirmed by the ability of BQ123 (1 microM) to reduce the
      maximum binding capacity of the HPMs for 125I-ET-1 by approximately 17%, without
      affecting the affinity for the radioligand. In conclusion, these results suggest
      that the HPM-SPA system contains predominantly (approximately 80%) ETB receptors,
      with a small ETA receptor population. These findings should be taken into account
      when this assay system is used to identify novel endothelin receptor ligands.

PMID- 7509924
TI  - Binding of 125I-endothelin-1 and 125I-endothelin-3 in rabbit saphenous vein:
      evidence for an atypical ET binding component.
AB  - Recent investigations have confirmed the presence of vasoconstrictory endothelinB
      (ETB) receptors in several tissues, including the rabbit saphenous vein (RSV). To
      determine the molecular nature of the ET receptor subtypes in RSV, radioligand
      receptor binding with selective ligands was conducted. ET-1 inhibited 125I-ET-1
      binding to RSV in a monophasic manner with an inhibition constant (Ki) of 0.08 +/
      0.03 nM. Inhibition of 125I-ET-1 binding by ET-3 or the ETA-selective peptide BQ
      123 resulted in markedly biphasic inhibition curves with Ki values of 0.4 +/- 0.1
      nM (36% of total sites)/37 +/- 10 nM (64% of total sites) for ET-3 and 10.4 +/-
      1.9 nM (70%)/3.2 +/- 0.9 microM (30%) for BQ-123. The correspondence of high
      affinity binding sites for BQ-123 with low-affinity binding sites for ET-3 agrees
      with the suggestion that 70% of the 125I-ET-1 binding sites in this tissue are
      ETA receptors. To further investigate the nature of the ET-B (non-ET-A) binding
      sites in RSV, 125I-ET-3 competition binding was conducted. ET-1 and BQ-123
      inhibited 125I-ET-3 binding in RSV with Ki values of 40 +/- 7 pM and 7.2 microM,
      respectively, while ET-3 and the ETB receptor-selective agonist sarafotoxin S6c
      (S6c) inhibition curves were best fit to two-site models. Resultant Ki values for
      ET-3 and S6c were 50 pM (71%)/4 pM (29%) and 0.3 nM (76%)/115 nM (24%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7509923
TI  - Design and synthesis of ETA receptor antagonists and study of ETA receptor
      distribution.
AB  - Many oligopeptides were designed to find ETA receptor antagonists on the
      hypothesis that an ETA receptor can recognize two hydrophobic parts of ET-1,
      i.e., Val-Tyr-Phe and Ile-Ile-Trp, over a short distance. They were synthesized
      from the benzyl ester of the C-terminal amino acid by stepwise chain elongation
      using the solution method. The binding affinity of the synthetic peptides to the
      endothelin receptors was examined in porcine cardiac ventricular muscle membrane
      for ETA receptor and in bovine whole brain membrane for ETB receptor.
      Hexamethyleneiminocarbonyl-Leu-trp-ala-beta ala-tyr-phe (TTA-386) was selected as
      an ETA receptor-selective competitive antagonist to ET-1. It competed against ET
      1 at ETA receptor sites and showed one-third the binding affinity of ET-1 for ETA
      receptor and < 1/10,000 the affinity for ETB receptor. It inhibited the ET-1
      induced increase of cytosolic free calcium concentration in A-10 cells. The 125I
      labeled hexapeptide (125I-TTA-386) was prepared to distinguish the distribution
      of ETA receptor from ETB receptor. Scatchard plot analysis of saturation binding
      of 125I-TTA-386 to porcine cardiac membranes showed the same Bmax value as that
      of 125I-ET-1. Autoradiographic studies showed that ETA receptors are most
      abundant in the cardiac muscle, intestine, large bowel, spleen, and testis.

PMID- 7509926
TI  - Endothelin receptor subtype(s) in rabbit jugular vein smooth muscle.
AB  - The goal of our study was to characterize pharmacologically the receptor
      subtype(s) that mediate endothelin-induced force development in the rabbit
      jugular vein. Endothelin-1 (ET-1), sarafotoxin S6c, and the linear endothelin
      peptide Ala11,15-ET-1[8-21] evoked approximately monophasic concentration
      dependent increases in force development in the rabbit jugular vein (rank order
      of potency: sarafotoxin S6c > ET-1 > Ala11,15-ET-1[8-21]). Maximally effective
      concentrations of the relatively ETB-selective (in comparison to ETA) ligands
      sarafotoxin S6c and Ala11,15-ET-1[8-21] produced significantly less force than a
      maximally effective ET-1 concentration (79 and 78% of ET-1 max., respectively; p
      < 0.001 for both). ET-3 produced a relatively shallow concentration-force
      relationship. Force evoked by ET-1 was minimally affected by the relatively ETA
      selective (in comparison with ETB) receptor antagonists BQ-123 and FR139317.
      These data indicate that the dominant functional ET receptor in rabbit jugular
      vein smooth muscle is of a non-ETA subtype.

PMID- 7509927
TI  - Endothelin ETA and ETB receptors mediate vascular smooth-muscle contraction.
AB  - Endothelin (ET) ETA receptors on vascular smooth muscle are believed to mediate
      the vasoconstrictor effects of ET isopeptides, and ETB receptors on the
      endothelium are thought to mediate the vasodilator effects. This study has
      investigated the receptors mediating endothelin-induced contraction of isolated
      ring preparations of rat thoracic aorta (RTA) and rabbit carotid artery (RCA),
      pulmonary artery (RPA), and jugular vein (RJV). In RTA and RCA, ET-1 (EC50 4.5
      and 5.2 nM, respectively) was 82- and 108-fold, respectively, more potent than ET
      3, whereas the ETB receptor-selective agonists sarafotoxin S6c (S6c) and
      Ala1,3,11,15-ET-1 (4-Ala-ET-1) were without effect up to > or = 1 microM. In
      contrast, in RPA and RJV, ET-1 (EC50 3.1 and 0.7 nM, respectively) and ET-3 (EC50
      4.4 and 0.9 nM, respectively) were equipotent, and 4-Ala-ET-1 (EC50 10.7 and 2.1,
      respectively) and S6c (EC50 0.4 and 0.1 nM, respectively) were potent contractile
      agonists. The ETA receptor antagonist BQ123 (D-Val-Leu-D-Trp-D-Asp-Pro)
      competitively antagonized the effects of ET-1 in RTA and RCA (pA2 values 6.9 +/-
      0.1 and 6.8 +/- 0.2, respectively) but did not antagonize (at 10 microM)
      contractions to ET-1, ET-3, or 4-Ala-ET-1 in RPA and RJV. In conclusion,
      contraction of vascular smooth muscle by endothelins can be mediated by both ETA
      and ETB receptors.

PMID- 7509928
TI  - Coupling of endothelin receptors to ion channels in rat glomerular mesangial
      cells.
AB  - Endothelin (ET) induces depolarization and contraction of glomerular mesangial
      cells (MCs), thereby influencing intraglomerular hemodynamics and filtration
      rate. In an attempt to clarify the ionic mechanism by which ET regulates MC
      function, we examined, using the whole-cell configuration of the patch-clamp
      technique, the effects of ET-1 and its related peptides, ET-3, sarafotoxin 6c
      (S6c), and IRL 1620, on ion currents and membrane potential in the primary
      culture of rat MCs. The resting potential of MCs was -48.4 +/- 1.9 mV (n = 23).
      It depolarized in response to ET-1, ET-3, and IRL 1620 by 14 (n = 7), 8 (n = 5),
      and 13 mV (n = 9), respectively. Whole-cell recording in combination with ion
      substitution ascertained the coexistence of potassium (IK) and chloride (ICl)
      currents. ET-1 (0.01-100 nM), ET-3 (1-100 nM), IRL 1620 (0.1-100 nM), and S6c
      (0.01-10 nM) augmented ICl in a concentration-dependent fashion, with ET-1 and
      S6c being the most potent. These actions were blocked by IRL 1038, a selective
      ETB receptor antagonist, but not by 1 microM BQ 123 (a selective ETA receptor
      antagonist) or 0.1 microM nifedipine (an L-type Ca(2+)-channel blocker). These
      results suggest a close coupling of the ETB receptor to ICl. ET-1, IRL 1620, and
      SRTX-6c in a similar concentration range also caused suppression of IK. This
      action was partially blocked by IRL 1038 and minimally affected by BQ 123,
      indicating a contributory role for ETB receptors in the regulation of
      IK.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509929
TI  - Binding characteristics of recombinant human endothelin receptors ETA and ETB
      expressed in baby hamster kidney cells.
AB  - Expression constructs for human endothelin (ET) receptors ETA and ETB were made
      by subcloning the corresponding coding sequences into the pMPSV/CMV vector. They
      were used together with plasmids bearing resistances to puromycin and hygromycin
      for transfection of baby hamster kidney cells. Culture in the presence of both
      antibiotics allowed the selection of cell lines stably expressing one receptor or
      the other. Competitive binding experiments using ET-1 and ET-3 showed the typical
      isopeptide-selective and non-isopeptide-selective profiles for recombinant ETA
      and ETB, respectively.

PMID- 7509930
TI  - Modulators of calcium and potassium channels: their effects on endothelin-1
      binding to cardiac membranes.
AB  - Endothelin-1 (ET-1) causes long-lasting vasoconstriction associated with a
      prolonged elevation of intracellular free Ca2+. Because this may be mediated
      through an effect on membrane ion channels, we investigated the effects of the
      dihydropyridine calcium channel antagonist nifedipine; two structurally distinct
      K+ channel openers, pinacidil and levcromakalim; and the inactive stereoisomer of
      levcromakalim (D-cromakalim), as well as ET-1 and ET-3, on binding of 125I
      labeled endothelin-1 to rat cardiac membranes. Specific binding of 125I-ET-1 was
      inhibited in a concentration-dependent manner by unlabeled ET-1 (IC50 = 1.56 +/-
      0.78 nM; slope = -0.49 +/- 0.10) and ET-3 (IC50 = 314 +/- 54 nM; slope = -0.34 +/
      0.11). Nifedipine, in concentrations < or = 10(-5) M, did not affect 125I-ET-1
      binding. However, levcromakalim significantly inhibited 125I-ET-1 binding
      (maximum binding 49 4/- 9%; p = 0.04), whereas the inactive isomer, D-cromakalim,
      had no effect. Pinacidil also inhibited 125I-ET-1 binding, although to a lesser
      extent than levcromakalim (maximum binding 63 +/- 7%). These findings provide
      evidence for a stereospecific interaction between K(+)-channel openers and ET-1
      binding in rat cardiac membranes. Because the slope of the logistic fit was
      substantially less than unity, and the effects of pinacidil and levcromakalim
      were incomplete, there may be two or more receptors for ET-1 in rat heart, only
      one of which is sensitive to K(+)-channel openers.

PMID- 7509931
TI  - Endothelin inhibits the calcium pump and stimulates phosphoinositide
      phospholipase C in liver plasma membranes via two different G proteins, Gs and
      Gq.
AB  - We have shown previously that in liver, endothelin (ET) binding to plasma
      membranes causes a rise in cytosolic calcium and activation of glycogenolysis.
      Here we show that the calcium extrusion pump in liver plasma membranes is
      inhibited by ET peptides, with ET-1 > or = ET-3 = sarafotoxin S6C-inhibition of
      the system being potentiated by GTP gamma S. Also, ET-1 stimulates PIP2
      hydrolysis in liver plasma membranes in a guanine nucleotide-dependent manner,
      with ET-1 > or = ET-3 = sarafotoxin S6C. In order to determine the nature of G
      protein(s) coupling of the ETB receptor to both effectors, antibodies against the
      C-terminus of different G-protein alpha-subunits were used. Antibodies reactive
      with Gs alpha blocked ET-1 inhibition of the calcium pump, but they had no effect
      on ET-1 stimulation of PIP2 hydrolysis. Antibodies reactive with Gq alpha dose
      dependently antagonized stimulation of PIP2 breakdown by ET-1 without affecting
      ET-1 inhibition of the calcium pump. Antibodies reactive with Gi1 alpha/Gi2 alpha
      had no effect on both systems. We conclude that the calcium signal induced by
      endothelins in hepatocytes may be consequent to both an activation of
      phospholipase C and inhibition of the calcium pump, both effectors being coupled
      to the ETB receptor by different G proteins, Gq and Gs, respectively.

PMID- 7509932
TI  - Endothelin subtype B receptors are coupled to adenylate cyclase via inhibitory G
      protein in cultured bovine endothelial cells.
AB  - We studied whether endothelin (ET) isopeptides have any effects on adenylate
      cyclase activity in cultured bovine endothelial cells (ECs). Both ET-1 and ET-3
      dose-dependently inhibited cAMP formation stimulated by forskolin and
      isoproterenol, although the inhibitory effect of ET-1 was less potent than that
      of ET-3. In contrast, ET-1 and ET-3 almost equipotently inhibited forskolin
      stimulated cAMP formation in bovine EC pretreated with phosphoramidon, a putative
      ET-1 converting-enzyme inhibitor. These data suggest that endothelial ETB
      receptors are functionally coupled to adenylate cyclase, possibly via Gi protein.

PMID- 7509933
TI  - Endothelin stimulates mitogen-activated protein kinase p42 activity through the
      phosphorylation of the kinase in rat mesangial cells.
AB  - We have reported that endothelin-1 (ET-1), which is a constrictor and mitogenic
      peptide, can increase mitogen-activated protein kinase p42 (p42mapk) activity in
      rat mesangial cells. In this study, we investigate the mechanism of activation of
      p42mapk. Treatment of quiescent mesangial cells with 10(-7) M ET-1 biphasically
      stimulated p42mapk activity. The kinetics of the immunoprecipitated p42mapk
      activity induced by ET-1 showed a maximal 3.5- to 4.5-fold stimulation 5 min
      after the addition of the agonist to the cell cultures and a smaller, 2.5-fold
      increase of activity between 2 and 6 h after ET challenge. Neither peak of
      p42mapk activity induced by ET-1 was inhibited by pretreatment of the cells with
      either cycloheximide to inhibit protein synthesis or actinomycin D to retard
      transcription. Analysis by immunoblot showed that p42mapk was not affected by
      these pretreatments. In addition, the kinetics of phosphorylation of p42mapk
      showed a significant 32P incorporation into p42 at 5, 30, and 240 min after ET
      stimulation. Because phosphorylation on tyrosine and threonine residues of the
      enzyme is necessary for activation of the kinase, we believe that the
      phosphorylation of the p42mapk rather than transcriptional or translational
      induction is responsible for the activation of p42mapk in mesangial cells
      stimulated with ET-1.

PMID- 7509934
TI  - Short-term regulation of endothelin receptor-mediated phosphoinositide hydrolysis
      and arachidonic acid release in A7r5 smooth-muscle cells.
AB  - In this study, the short-term regulation of endothelin-1-(ET-1) induced
      phosphoinositide (PI) hydrolysis and arachidonic acid release were investigated
      in cultured rat aortic smooth-muscle cells. ET-1, but not the ETB-selective
      peptide sarafotoxin (SFX) S6c, induced a dose-dependent increase in [3H]inositol
      phosphate release (EC50 = 0.4 +/- 0.1 nM). ET-3 stimulated this response only at
      concentrations > 0.1 microM. The ETA receptor antagonist BQ-123 inhibited ET-1
      induced PI turnover, with an IC50 value of 97 +/- 15 nM. Pre-exposure of intact
      cells to ET-1 resulted in a 72% and 73% reduction in the ability of ET-1 or SFX
      S6b, respectively, to stimulate [3H]inositol phosphate release, without affecting
      the response to vasopressin. In contrast, PI turnover induced by ET-1 or SFX S6b
      was only slightly lowered, by 28% and 22%, after a 30-min preincubation period
      with SFX S6b. ET-1, but not SFX S6c, also stimulated [3H]arachidonic acid release
      by two-fold (EC50 = 3 +/- 0.8 nM). Pretreatment of intact cells with neomycin or
      phorbol-12-myristate-13-acetate resulted in a 49% and 44% inhibition of ET-1
      induced [3H]inositol phosphate accumulation but did not decrease ET-1-stimulated
      [3H]arachidonic acid release, suggesting that these responses are separately
      regulated events in these cells.

PMID- 7509935
TI  - Endothelin-1 displaces [3H]nicardipine binding in sections of human renal artery.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, the actions of which are
      mediated through interaction with specific ET receptors. Functional evidence has
      shown that the constrictor effect of ET may require extracellular Ca2+. Ca2+
      antagonists of the dihydropyridine family attenuate the vasoconstriction caused
      by ET. However, the basis of the interactions between ET and dihydropyridine
      agents are not well understood. Our study was designed to assess whether
      different concentrations of ET-1 or ET-3 have any effect on [3H]nicardipine
      binding to sections of human renal artery. [3H]Nicardipine was specifically bound
      to sections of the human renal artery. Binding sites, which were located
      primarily over smooth muscle of the tunica media, showed the pharmacologic
      profile typical of a dihydropyridine Ca2+ channel. Increasing concentrations of
      ET-1, but not of ET-3, competed dose-dependently with [3H]nicardipine binding. A
      1-nM concentration of ET-1 lessened specific [3H]nicardipine binding by
      approximately 80%. These results suggest the occurrence of an interaction in the
      human renal artery between dihydropyridine Ca2+ channels and ET-1. This
      interaction probably accounts for the inhibition of the ET-1-mediated
      vasoconstriction elicited by nicardipine.

PMID- 7509936
TI  - Autocrine role of endothelin in rat inner medullary collecting duct: inhibition
      of AVP-induced cAMP accumulation.
AB  - Exogenous endothelin-1 (ET-1) inhibits arginine vasopressin (AVP)-induced cAMP
      accumulation in the inner medullary collecting duct (IMCD). Because ET-1 is
      produced by and binds to specific receptors on the IMCD, the possibility exists
      that ET-1 is an autocrine regulator of AVP action in this nephron segment. To
      test this hypothesis, rat IMCD cells were grown on semipermeable membranes in the
      presence of rabbit anti-ET-1 antiserum or nonimmune rabbit serum (NRS). AVP (10(
      9) M) caused a 2.5-fold greater accumulation of cAMP in confluent IMCD monolayers
      preincubated in ET-1 antiserum in comparison with NRS. ET-1 (10(-8) M) inhibited
      the AVP-induced rise in cAMP by 65% in cells preincubated in ET-1 antiserum but
      had no effect in NRS-treated cells. Finally, [125I]-ET-1 (30 pM) binding was
      increased sixfold in IMCD preincubated in anti-ET-1 antiserum. These data
      indicate that ET-1 causes tonic autocrine inhibition of AVP responsiveness in the
      IMCD.

PMID- 7509937
TI  - Endothelin-1 and -3 binding to ETB receptors in rat renal tubules.
AB  - To increase understanding of endothelin (ET) function in the kidney, we
      investigated binding of the radioligand of endothelin isopeptides to
      microdissected rat nephron segments. Specific ET-1 binding was highest in the
      inner medullary collecting duct, whereas the cortical and outer medullary
      collecting ducts showed moderate binding, as did the glomeruli. There was slight
      ET-1 binding to the early portion of the proximal tubule. Other nephron segments
      displayed little ET-1 binding. The binding profile of ET-3 along the nephron
      markedly resembled that of ET-1. Scatchard analyses of ET-1 and ET-3 binding to
      cortical collecting ducts revealed a single class of receptor for both ET-1 and
      ET-3. Displacement of [125I]-ET-1 binding by unlabeled ET-3 was similar to that
      produced by unlabeled ET-1. Moreover, a specific ETB agonist, BQ-3020, almost
      completely inhibited [125I]-ET-1 binding in cortical collecting ducts, whereas a
      specific ETA antagonist, BQ-123, had little effect. These data indicate that
      cortical collecting ducts express ETB receptors, to which both ET-1 and ET-3 bind
      equally.

PMID- 7509938
TI  - Endothelin-2 mRNA splice variants detected by RT-PCR in cultured human vascular
      smooth muscle and endothelial cells.
AB  - Our aim was to examine the hypothesis that vascular smooth-muscle cells (VSMCs)
      express only ETA mRNA and endothelial cells express only ETB mRNA and to
      determine which ET mRNA isoforms are expressed in these cell cultures. Using the
      reverse transcriptase polymerase chain reaction, we were able to detect ETB, ET-1
      and splice variant ET-2 mRNA in cultured human umbilical vein endothelial cells
      (HUVECs) and ETA and splice variant ET-2 mRNA in cultured aortic smooth-muscle
      cells. The presence of ET-2 mRNA in cultured VSMCs has not been previously
      reported. These results agree with the hypothesis that ET-1 may be released from
      vascular endothelial cells to act predominantly on ETA receptors on VSMCs to
      stimulate contraction of the underlying smooth-muscle cells, and that endothelium
      derived relaxing factor release may be mediated predominantly via the ETB
      receptors on HUVECs. The role of ET-2 expression from HUVECs and VSMCs is less
      clear.

PMID- 7509939
TI  - Endothelin-3 increases transmission in the rabbit pulmonary parasympathetic
      nervous system.
AB  - The effect of endothelin-3 (ET-3) on the response to parasympathetic nerve
      stimulation of rabbit isolated bronchus was examined. The site of action of ET-3
      in the pulmonary parasympathetic nervous system was also investigated. ET-3
      induced a concentration-dependent increase in the response to electrical field
      stimulation. The response was atropine sensitive and therefore cholinergically
      mediated. At a concentration of 10 nM, ET-3 increased the response to field
      stimulation to 205 +/- 42% of the initial response. The effect was concentration
      related, as 100 nM further increased this response to 315 +/- 69%. The
      responsiveness of the tissue to exogenous acetylcholine was not affected by ET-3.
      Therefore ET-3 has a neuromodulatory role on cholinergic parasympathetic
      transmission in rabbit airways exerted at a prejunctional site.

PMID- 7509940
TI  - Heterogeneous receptors mediate endothelin-1-induced changes in blood pressure,
      hematocrit, and platelet aggregation.
AB  - Using selective endothelin (ET) receptor antagonists, we investigated which ET
      receptor subtypes mediate the changes in blood pressure and hematocrit produced
      by intraarterial injection of ET-1 in the anesthetized rabbit. In addition, the
      receptor through which ET-1 stimulates the release of prostacyclin (PGI2) and,
      hence, inhibits ex vivo platelet aggregation, was identified. FR 139317 (ETA
      antagonist, 0.6 mg kg-1 min-1 preceded by a loading dose of 3 mg kg-1 i.v.) and
      PD 145065 (nonselective ETA/ETB antagonist, 0.6 mg kg-1 min-1 preceded by a
      loading dose of 3 mg kg-1 i.v.) attenuated the ET-1 (1 nmol kg-1 i.a.)-induced
      rise in mean arterial pressure (MAP) by 89% and 75%, respectively. In contrast to
      FR 139317, PD 145065 also abolished the initial, transient depressor response
      brought about by ET-1. ET-1 caused a significant increase in hematocrit 15 min
      after its injection. PD 145065 caused a significantly greater inhibition of this
      hemoconcentration than FR 139317. ET-1 inhibited ex vivo platelet aggregation by
      96%, measured 5 min after injection of the peptide. PD 145065, but not FR 139317,
      abolished the antiaggregatory effects of ET-1. Thus, the ET-1-induced
      vasoconstriction in the anesthetized rabbit is predominantly mediated via the ETA
      receptor, whereas the depressor and antiaggregatory actions of ET-1 are caused by
      activation of the ETB receptor. Moreover, activation of both receptor subtypes by
      ET-1 accounts for the increase in hematocrit produced by ET-1 in vivo.

PMID- 7509941
TI  - Effects of endothelin on fluid and NaCl absorption across the jejunum in
      anesthetized dogs.
AB  - The aim of the present study was to investigate the effects of endothelin (ET) on
      fluid and NaCl absorption across the jejunum. Dogs were anesthetized with
      pentobarbital sodium (30 mg/kg i.v.). Polyethylene catheters were placed in the
      superior mesenteric arteries and portal vein for infusions and to measure
      arterial and portal venous pressure. Superior mesenteric arterial blood flow was
      continuously measured with an ultrasonic flow probe. A 30-cm-long jejunal loop
      was made at 10 cm from the duodenal fossa. Infusion of saline, ET-1, ET-3, or
      phenylephrine (PE) was initiated 10 min before pouring the test solution into the
      jejunal loop and continued for 25 min. The net fluid (7.2 +/- 0.9 ml, mean +/-
      SE, n = 8), Na+ (1.1 +/- 0.1 mEq), and Cl- (1.1 +/- 0.2 mEq) absorption during
      saline infusion was not significantly different from those (7.0 +/- 1.0 ml, 1.1
      +/- 0.1 mEq, and 1.1 +/- 0.2 mEq) during ET-1 infusion but was significantly
      decreased to 4.8 +/- 0.6 ml, 0.7 +/- 0.1 mEq, and 0.7 +/- 0.1 mEq by ET-3
      infusion. ET-1 increased the mesenteric vascular resistance by 84.7 +/- 23.4% and
      ET-3 by 64.3 +/- 7.5%. To study the underlying mechanisms, the absorption
      experiment was performed after the increase in vascular resistance and
      administration of nitric oxide (NO) synthase inhibitor. We increased the
      resistance by 127.8 +/- 12.6% with PE and found no effect. Pretreatment with NO
      synthase inhibitor did not influence the decreased absorption induced by ET-3. In
      conclusion, ET-3 suppresses jejunal absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509943
TI  - Action of endothelin-1 on vasomotor neurons in rat rostral ventrolateral medulla.
AB  - Intracisternal administration of endothelin-1 (ET-1) elicits sympathetically
      mediated cardiovascular responses by acting on the ventral surface of the medulla
      oblongata (VSM) subjacent to the rostral ventrolateral medulla (RVLM). We
      examined, in urethane-anesthetized rats, whether intracisternal ET-1 affected
      activity of vasomotor neurons (VMNs) in the RVLM, by acting either directly on
      the VMNs or indirectly via the VSM. VMNs were identified electrophysiologically.
      Intracisternal administration of ET-1 altered activity of all the 13 VMNs tested.
      At a dose of 0.1 pmol, ET-1 invariably caused transient excitation in six VMNs
      examined, whereas at a dose of 1 pmol in separate experiments all the seven VMNs
      tested were inhibited with (n = 6) or without (n = 1) preceding excitation.
      Similarly, topical application of ET-1 (0.1-1 pmol) to the VSM caused inhibition
      with (n = 3) or without (n = 2) preceding excitation in all the five VMNs tested.
      Direct iontophoretic application of ET-1 to the VMNs caused excitation in four of
      seven VMNs examined but did not affect the other three neurons. These results
      support the view that intracisternally administered ET-1 alters activity of VMNs
      in the RVLM, by acting directly on neurons themselves and indirectly via the VSM.

PMID- 7509942
TI  - Conversion of big endothelin-1 in rat uterus causes contraction mediated by ETA
      receptors.
AB  - Like endothelin-1 (ET-1), its immediate human precursor big ET-1 (1-100 nM)
      increased the rate of spontaneous phasic contractions and caused graded tonic
      contractions of isolated rat uterus strips. The tonic contraction to big ET-1 (10
      nM) was markedly blocked by phosphoramidon (100 microM), which did not modify the
      response to an equipotent concentration of ET-1 (3 nM). Responses to big-ET-1 (30
      nM) were abolished in calcium-free medium, but those to ET-1 (10 nM) were only
      reduced by this condition. The EC50 of big ET-1 for inducing tonic contraction
      was only sevenfold greater than that of ET-1, and both peptides produced a
      maximal response similar to that evoked by KCl 80 mM. ET-3 was much less potent.
      The selective ETA receptor antagonist BQ-123 (40-600 nM) caused graded rightward
      shifts of the ET-1 curve without affecting the maximal response, yielding a
      Schild plot with a slope not different from unity and a pA2 value of 7.76. BQ-123
      (100 nM) did not affect contractions induced by oxytocin (5 nM), acetylcholine (3
      microM), or bradykinin (0.3 nM), but inhibited responses to both big ET-1 and ET
      1. Therefore, the rat uterus contains a phosphoramidon-sensitive, calcium
      dependent endothelin-converting enzyme that readily converts big ET-1 into ET-1,
      which then contracts the myometrium via activation of ETA receptors.

PMID- 7509944
TI  - The snake venom peptide sarafotoxin S6b inhibits repetitive platelet thrombus
      formation in the stenosed canine coronary artery.
AB  - Various snake venom peptides have been extensively evaluated for use as
      antithrombotic agents. Recently, it was determined that the snake venom peptide
      sarafotoxin S6b (S6b) is structurally similar to the potent vasoactive hormone
      endothelin-1 (ET-1), which has been shown to inhibit agonist-induced platelet
      aggregation. The potential in vivo antithrombotic activity of S6b was compared
      with that of ET-1, a much more potent pressor agent than S6b, by evaluating the
      effects of S6b and ET-1 (0.5 microgram/kg i.v.) on repetitive platelet thrombus
      formation (RPTF) in the stenosed canine circumflex coronary artery. In this model
      platelets adhere to the damaged vessel wall near a mechanically produced
      stenosis. As platelets aggregate at this site, blood flow gradually declines
      until the vessel is completely occluded. The thrombus is then physically
      dislodged, thus restoring flow. The blood flow pattern resulting from RPTF is
      referred to as cyclic flow reductions (CFRs). Injection of S6b or ET-1 blocked
      RPTF, as indicated by inhibition of CFRs. On a rating system of 0 (no effect) to
      3 (complete inhibition), S6b and ET-1 produced CFR ratings of 1.8 +/- 0.5 (n = 6)
      and 2.0 +/- 0.4 (n = 6), respectively. This effect was not blocked by
      pretreatment with aspirin at 5 mg/kg i.v., a dose that abolishes arachidonic acid
      induced ex vivo platelet aggregation (CFR scores for S6b and ET-1 were 2.6 +/-
      0.2, n = 5 and 2.0 +/- 0.3, n = 5, respectively).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7509945
TI  - Endothelin-1 and aggregation of human platelets in vitro.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by endothelial
      cells. We investigated whether ET-1, like other potent endothelium-derived
      vasoactive agents, interacts directly with human platelets in vitro. Platelet
      rich plasma was obtained from healthy male volunteers and incubated with ET-1 (1
      microM) or vehicle (sodium chloride 154 mM) for 10 min at 37 degrees C. Platelet
      aggregation was measured by the Born method, using light transmittance through
      the plasma sample as an index of activation. Although a significant increase in
      light transmittance was observed when plasma was incubated with ET-1 compared
      with vehicle, (3.8 +/- 0.4% versus 2.7 +/- 0.2%; n = 24; p = 0.038), this effect
      was small and is unlikely to be of biologic significance. To investigate the
      possibility that ET-1-stimulated platelet nitric oxide (NO) synthesis might be
      masking a direct aggregatory effect of ET-1, in a second study in six subjects NG
      monomethyl-L-arginine (L-NMMA, 10 and 100 microM), an inhibitor of NO synthase,
      was preincubated with the plasma before the addition of ET-1 (1 nM and 1 microM).
      No significant difference was observed whether samples were incubated with L-NMMA
      alone or with L-NMMA and ET-1. The results of this study suggest that ET-1 does
      not have a major direct effect as a platelet aggregating agent.

PMID- 7509946
TI  - Endothelin-renin-angiotensin-atrial natriuretic peptide system in ovaries: an
      intraovarian ERAANP system.
AB  - In a recent investigation of the ovary, high levels of endothelin-1 (ET-1), the
      renin-angiotensin system (RAS), and atrial natriuretic peptide (ANP) were
      identified. It was determined that ET, RAS, and ANP, alone or together, affected
      ovarian function. It is important that mutual relationships of these vasoactive
      and hormonal peptides, which coexist in the ovary, are examined to determine
      their in vivo functions. This study, using immature rats treated with pregnant
      mare's serum gonadotropin (PMS), examined the effects of ET-1, angiotensin II
      (Ang II) and ANP, individually or in combination, on steroidogenesis by granulosa
      cells (GCs) cultured for 72 h. ET-1 Ang II, and ANP, alone or combined, also had
      a mutual effect on steroidogenesis. Concomitantly with previous findings on the
      ovary, the authors propose that the intraovarian endothelin-renin-angiotensin-ANP
      system (ERAANPS) functions as a novel intraovarian regulator system.

PMID- 7509947
TI  - Two receptor subtypes are involved in the contractile component of the guinea pig
      ileum responses to endothelins.
AB  - Endothelin-1 (ET-1) and endothelin-3 (ET-3) induced a biphasic response
      (relaxation and contraction) in the guinea pig ileum. Short-term activation of
      protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu) inhibited the
      contractile but not the relaxing component of the responses, as did H-7. Long
      term pretreatment with PDBu reversed the short-term inhibition but did not affect
      the tachyphylaxis induced by ET-1. These results suggest that PKC contributes to
      ET-1 contraction but not to tachyphylaxis. The ETA antagonist BQ-123, at 34 nM,
      competitively inhibited ET-1 contraction, but at 340 nM the inhibition was
      noncompetitive. Dose-response curves for ET-1 relaxation were shifted to the
      left. For ET-3, BQ-123 (340 nM) only decreased the maximal contractile response
      of the dose-response curve without affecting the relaxation. We suggest that in
      this tissue there is one receptor for ET-1-induced contraction, which is
      competitively antagonized by BQ-123, and another one for ET-3-induced
      contraction, which is noncompetitively antagonized by BQ-123.

PMID- 7509948
TI  - Endothelin-1 binding sites and immunoreactivity in the cultured human placental
      trophoblast: evidence for an autocrine and paracrine role for endothelin-1.
AB  - In human placenta, endothelin (ET) could derive from maternal, fetal, and/or
      endogenous sources. Therefore, localization of ET-1 was investigated by
      immunohistochemistry in human term placenta and in cultured trophoblasts. In
      sections of placenta, ET-1 immunoreactivity (ET-1 IR) was specifically detected
      in the endothelium of the vessels and in the syncytiotrophoblasts of the villi.
      ET-1 IR was also detected in the decidual cells and in the extravillous
      cytotrophoblasts of the basal plate. The extravillous cytotrophoblasts of the
      chorionic plate and of the placental septa also exhibited strong ET-1 IR. For
      trophoblast culture, cytotrophoblastic cells were obtained from placental villi
      by trypsin-DNAse dispersion, further purified on a Percoll gradient, and enriched
      by employing a monoclonal anti-HLA class I antibody. After different periods of
      culture of purified cytotrophoblastic cells (1-5 days), ET-1 IR was observed in
      95% of cells: cytotrophoblastic cells, trophoblast aggregates, and
      syncytiotrophoblasts. The presence of ET-1,2 immunoreactivity (ET-1,2 IR) in the
      culture media was demonstrated by radioimmunoassay. A uniform daily production of
      the peptide was observed over at least 5 days (approximately 50 fmol/10(6)
      cells/24 h). Furthermore, trophoblastic cells that had been cultured for 5 days
      contained significant amounts of ET-1,2 IR (24 fmol/10(6) cells). These results
      suggest a trophoblastic origin for ET-1 and support the hypothesis of a paracrine
      and autocrine action of the peptide in the physiology of the trophoblast and
      placenta.

PMID- 7509949
TI  - Structure-activity relationships of ET-1 and selected analogues in the isolated
      guinea pig trachea: evidence for the existence of different ETB receptor
      subtypes.
AB  - We tested endothelin-1 (ET-1) derivatives on the guinea pig trachea (GPT) and
      compared their biologic activities to ET-1 in this tissue and to published
      reports using similar analogues in different assay systems, such as vascular
      smooth-muscle preparations. Six ET-1 analogues with no intramolecular disulfide
      bridges and/or with the substitution of one or more amino acids at position 7
      and/or 21 were synthesized. Oxidation of the Met7 or formylation of the indole
      moeity of the Trp21 did not affect the biologic activity of ET-1 on the trachea.
      Acetamidomethylation of the Cys1-15 decreased the potency and intrinsic activity,
      but not as much as had been reported on vascular preparations. However,
      modifications involving one or both disulfide bridges, combined with formylation
      of the Trp21, yielded analogues with very weak contractile activity. These
      findings, when compared with the biologic activity of ET-1 analogues in other
      assay systems, suggest that a different population of receptors, probably non-ETA
      (i.e., an ETB subtype different from the one reported to be involved in ET-1
      induced binding or activities in rabbit pulmonary artery or in rat cerebellum or
      vasculature) is present and responsible for ET-1-induced bronchoconstriction on
      the GPT.

PMID- 7509950
TI  - Human endothelin receptors characterized using reverse transcriptase-polymerase
      chain reaction, in situ hybridization, and subtype-selective ligands BQ123 and
      BQ3020: evidence for expression of ETB receptors in human vascular smooth muscle.
AB  - Our aim was to characterize and determine the function of endothelin (ET)
      receptor subtypes in human vascular tissue. Reverse transcriptase-polymerase
      chain reaction with nested oligonucleotide primers detected the presence of mRNA
      encoding both ETA and ETB receptors in the media from aorta and pulmonary and
      coronary arteries. In situ hybridization confirmed the presence of mRNA for both
      subtypes in the media of coronary arteries. Saturation binding assays using 125I
      ET-1 found a single population of high-affinity ET receptors (n = three patients,
      +/- SEM) in aorta (Kd = 0.507 +/- 0.020 nM; Bmax = 9 +/- 4 fmol/mg protein) and
      pulmonary (Kd = 0.845 +/- 0.245 nM; Bmax = 15 +/- 10 fmol/mg protein) and
      coronary arteries (Kd = 0.141 +/- 0.020 nM; Bmax = 71 +/- 21 fmol/mg protein).
      Using media from coronary arteries, the ETA-selective ligand BQ123 (cyclo[D-Asp-L
      Pro-D-Val-L-Leu-D-Trp]) and the ETB-selective ligand BQ3020 (Ala11,15-Ac-ET-1[6
      21]) both produced biphasic competition binding curves against 125I-ET-1,
      confirming the presence of high- and low-affinity sites corresponding to the two
      subtypes: BQ123 (KdETA = 0.85 +/- 0.03 nM; KdETB = 7.58 +/- 2.27 microM; ETA/ETB,
      87%:13%) and BQ3020 (KdETA = 0.22 +/- 0.04 microM; KdETB = 0.77 +/- 0.34 nM;
      ETA/ETB, 62%:38%). BQ123 (0.1 microM) caused a significant parallel rightward
      shift of ET-1-induced vasoconstriction of coronary arteries in vitro, but BQ3020
      and Ala1,3,11,15-ET-1 failed to show any agonist activity when tested at
      concentrations of < or = 3 microM in three vessels.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7509951
TI  - Cellular mechanism of endothelin-induced nitric oxide synthesis by cultured
      bovine endothelial cells.
AB  - Endothelins (ETs) cause initial and transient vasodilation via an endothelium
      dependent mechanism. We studied the cellular mechanism by which ETs stimulate
      synthesis and release of endothelium-derived relaxing factor (EDRF)/nitric oxide
      (NO) in cultured bovine endothelial cells (EC). ET-1 and ET-3 rapidly (within 1
      min) and dose-dependently (10(-10) to 10(-7) M) stimulated production of
      nitrate/nitrite (NOx) in bovine EC; ET-3 was more potent than ET-1 at generating
      endothelial NOx. The ET-3-stimulated NOx production was completely abolished by a
      NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA), the effect of which was
      reversed by coadministration of excess L-arginine. NOx production stimulated by
      ET-3 was blocked by an intracellular Ca2+ chelator but not by an extracellular
      Ca2+ chelator. A selective calmodulin inhibitor W-7 dose-dependently inhibited
      the ET-3-stimulated NOx production, whereas a nonselective calmodulin inhibitor W
      5 failed to affect NOx production. These data suggest that ETs stimulate receptor
      mediated EDRF/NO synthesis via a Ca2+/calmodulin-dependent pathway in vascular
      endothelial cells.

PMID- 7509952
TI  - Endothelins and membrane potential of vascular smooth muscle of the canine
      coronary artery.
AB  - We investigated the effects of endothelins on the membrane potential of vascular
      smooth-muscle cells of canine coronary artery, using glass microelectrodes. In
      tissues with endothelium, endothelin-1 (ET-1), from 10(-12) to 10(-9) M, did not
      alter the membrane potential. Higher concentrations of the peptide produced
      sustained depolarization without detectable hyperpolarization. Endothelin-3 (ET
      3, 10(-11) to 10(-8) M) did not produce significant membrane hyperpolarization in
      tissues with endothelium. Prostaglandin F2 alpha (10(-5) M) depolarized the cell
      membrane by about 6 mV. ET-1 (10(-9) M) did not evoke detectable
      hyperpolarization in the presence of prostaglandin F2 alpha. In tissues incubated
      with BQ123 (10(-6) M, a selective ETA-receptor antagonist), which attenuated the
      depolarization evoked by ET-1, both isopeptides did not produce detectable
      hyperpolarization. These findings suggest that ET-1 and ET-3 do not evoke the
      release of endothelium-derived hyperpolarizing factor in the canine coronary
      artery.

PMID- 7509954
TI  - ETA-dependent pressor effects and release of prostacyclin induced by endothelins
      in pulmonary and renal vasculature.
AB  - BQ-123, a selective endothelin A (ETA) receptor antagonist, was used to study the
      receptors involved in the ET-1-induced release of prostacyclin (PGI2) in perfused
      rat lung and rabbit kidney and the pressor effects of ET-1 in rabbit renal
      vasculature. In perfused rat lung, infusion of ET-1 (5 nM) significantly
      increased the release of PGI2, which was markedly reduced after a 15-min infusion
      of BQ-123 (1 microM). In rabbit kidney, the PGI2 release induced by ET-1 (10 nM)
      was abolished by a 15-min pretreatment with BQ-123 (1 microM). In both
      preparations the ET-1-induced release of PGI2 was fully restored 60 min after the
      interruption of BQ-123 infusion. In rabbit kidney a dose-dependent increase of
      perfusion pressure was also observed after bolus injections of ET-1 (5 and 10
      pmol). The pressor responses to ET-1 were abolished by BQ-123 (0.1 microM), and
      60 min after interruption of the infusion of the antagonist, the responses to ET
      1 were restored to 68% and 99% of control values, respectively. Two selective ETB
      receptor agonists, IRL 1620 and BQ-3020, were inactive as pressor and prostanoid
      releasing agents at doses and concentration 25-50 times higher than for ET-1 in
      perfused rabbit kidney. A higher concentration of BQ-123 (1 microM) did not
      modify the pressor responses to angiotensin II (5 nmol). Our results support the
      hypothesis that ET-1-induced release of vasodilatory prostanoids from perfused
      rat lung and rabbit kidney and constriction of rabbit renal vasculature are
      triggered by activation of ETA receptors.

PMID- 7509953
TI  - Possible contribution of potassium channels to the endothelin-induced dilatation
      of rat coronary vascular beds.
AB  - The mechanism for the endothelin (ET)-induced vasodilatation of the endothelium
      intact rat coronary vascular bed was investigated. Continuous infusion (0.1-1 nM)
      or bolus injection (1-100 pmol) of ET-1 or ET-3 elicited a dose-related transient
      decrease, followed by a slight sustained increase, in the coronary perfusion
      pressure (CPP). The decrease in CPP induced by an injection (10 pmol) of ET-1 or
      ET-3 was not modified by indomethacin (5 microM). However, oxyhemoglobin (5 mM)
      shortened the duration of the ET-induced decrease in CPP, although it did not
      affect the magnitude. The ET-induced decrease in CPP was abolished by raising K+
      in the perfusing solution from 5.9 to 16.9 mM. These findings suggest that the ET
      induced dilatation of the rat coronary vascular beds may not be mediated by
      cyclooxygenase products. The ET-induced vasorelaxation may be mediated, at least
      in part, by endothelium-derived relaxing factor and may be related to opening of
      K+ channels.

PMID- 7509955
TI  - Implication of different endothelin receptors in the vascular action of a
      hypertensive dose of ET-1 in rat.
AB  - The role of different endothelin (ET) receptors in the hemodynamic action of ET-1
      was investigated with an ETA-receptor antagonist, BQ-123, in anesthetized Wistar
      rat. BQ-123 (10 mg/kg/0.1 ml) was injected 5 min before ET-1 injection (1
      nmol/kg). IV injection of ET-1 induced a short period of hypotension associated
      with aortic vasodilation, followed by long-lasting hypertension and aortic
      vasoconstriction. These effects were concomitant with immediate renal and
      mesenteric vasoconstriction. In the presence of BQ-123, the hypotension and
      aortic vasodilation induced by ET-1 were prolonged and the subsequent
      hypertension and aortic constriction were prevented. In the renal vascular bed,
      BQ-123 did not significantly affect the initial ET-1-induced constriction but
      markedly shortened its duration. In contrast, in the mesenteric vascular bed, BQ
      123 seemed initially to amplify the ET-1-induced constriction, but afterwards
      slightly reduced it. The hemodynamic response to ET-1 may be mediated at first by
      ETB receptors, which induce a reduction of systemic blood pressure and regional
      vasoconstriction. In a second phase, ETA receptors operate to induce a systemic
      pressor effect and participate with ETB receptors in regional vasoconstriction.
      Therefore, ETA and ETB receptors may exist in various proportions in different
      vessels, the renal vascular bed appearing to be richer in ETA receptors than the
      mesenteric bed. The results, which demonstrate that ETB receptors mediate aortic
      dilation and regional constriction, are unexpected and suggest the existence of
      another non-ETA-type receptor and/or a different localization of non-ETA
      receptors in the vascular wall.

PMID- 7509957
TI  - Two subtypes of the endothelin receptor (ETA and ETB) mediate vasoconstriction in
      the perfused rat heart.
AB  - The effects of endothelin-1 (ET-1) are mediated by two subclasses of the
      endothelin receptor, ETA and ETB. The Langendorff perfused rat heart was used to
      determine the endothelin receptor subtype mediating rat coronary
      vasoconstriction. ET-1 (EC50 = 1.5 x 10(-10) M) and endothelin-3 (ET-3) (10(-11)
      3 x 10(-8) M) caused dose-dependent increases in coronary perfusion pressure. BQ
      123, a selective antagonist of the ETA-receptor subtype, did not cause a parallel
      shift in the dose-response curves of ET-1 or ET-3. In the presence of 1-3 x 10(
      6) M BQ-123, ET-1 and ET-3 exhibited biphasic dose-response curves, suggesting
      that vasoconstriction was caused by two receptors. The ETB-selective agonist Suc
      [Glu9,Ala11,15]-ET-1(8-21) (IRL 1620) maximally increased perfusion pressure by
      approximately 50% of the maximal response to ET-1 and was not inhibited by BQ
      123. These data suggest that the rat coronary vasoconstrictor effects of ET-1 and
      ET-3 are mediated by both ETA and ETB receptors.

PMID- 7509956
TI  - Differential responsiveness of conduit and resistance coronary arteries to
      endothelin A and B receptor stimulation in anesthetized dogs.
AB  - The effects of endothelin-1 (ET-1), an ET(A)/ETB-receptor agonist, and IRL 1620,
      a potent and selective ETB-receptor agonist, were assessed on left circumflex
      coronary artery diameter (sonomicrometry) and flow (electromagnetic flow probe)
      in pentobarbital-anesthetized dogs. Intracoronary (i.c.) bolus injections of ET-1
      (80 pmol/dose) caused large, sustained coronary diameter decreases (281 +/- 39
      microns) and transient flow increases (5.6 +/- 2.6 ml/min), followed by transient
      (10.0 +/- 1.9 ml/min) and then sustained flow reductions (6.6 +/- 2.5 ml/min)
      before terminating in ventricular fibrillation after two to five doses (max delta
      s; n = 4 dogs). IRL 1620 boluses (5-2,000 pmol/dose i.c.; max delta s; n = 3)
      also dose-dependently and transiently increased (16.8 +/- 1.4 ml/min; 200 pmol),
      then transiently decreased (12.8 +/- 1.5 ml/min; 1,600 pmol) flow but had minimal
      effects on diameter (delta = -23 +/- 4 microns; 2,000 pmol). Doses of IRL 1620
      beyond 400 pmol were accompanied by a slowly responding, sustained decrease in
      baseline flow (-9.2 +/- 2.7 ml/min) and baseline diameter (232 +/- 150 microns).
      In a separate group of dogs (n = 5), IRL 1620 (400 pmol i.c.) was evaluated
      before and after sequential inhibition of cyclooxygenase (indomethacin; 10 mg/kg
      i.v.) and then nitric oxide synthase (N omega-nitro-L-arginine methyl ester, L
      NAME; 50 mg/kg i.v.). Indomethacin alone did not affect the flow increase to IRL
      1620 (11.0 +/- 2.0 versus 11.8 +/- 1.8 ml/min) but blunted the flow decrease by
      30 +/- 6% (10.6 +/- 1.4 versus 7.1 +/- 0.7 ml/min).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7509959
TI  - Inhibition by atrial natriuretic peptide of endothelin-1-stimulated proliferation
      of vascular smooth-muscle cells.
AB  - The effect of endothelin-1 (ET-1) on proliferation of aortic vascular smooth
      muscle cells (VSMCs) from spontaneously hypertensive (SHRs) and normotensive
      Wistar-Kyoto (WKY) rats was assessed by the measurement of [3H]-thymidine
      incorporation into DNA. ET-1 stimulated DNA synthesis in a concentration
      dependent manner. Half-maximal stimulation occurred at a concentration of 7 x 10(
      11) M. Three separate administrations of ET-1 to the cell cultures resulted in a
      half-maximal stimulation at 3 x 10(-12) M in of VSCMs from SHRs. VSMCs from SHRs
      responded to a far greater extent compared with WKY rats. The stimulatory effect
      of ET-1 was significantly attenuated by atrial natriuretic peptide (ANP).
      Repeated administration of ANP led to exacerbation of the inhibitory effect.
      Serum-stimulated DNA synthesis was not influenced by ANP. The proliferative
      action of ET-1 and the inhibition by ANP are discussed with respect to the
      development of vascular disease in atherosclerosis and hypertension.

PMID- 7509958
TI  - The ETA antagonist BQ-123 inhibits anoxic contractions of canine coronary
      arteries without endothelium.
AB  - Experiments were designed to determine whether or not endogenous endothelin (ET)
      contributes to endothelium-independent anoxic contractions of canine coronary
      arteries. Rings without endothelium were suspended for isometric tension
      recording in conventional organ chambers filled with modified Krebs-Ringer
      bicarbonate solution. Anoxia (PO2 < or = 1 mm Hg) caused reproducible
      contractions. The anoxic contractions were augmented by exogenous endothelin-1
      (ET-1). At 10(-6) M and 10(-5) M, BQ-123 (a specific endothelin antagonist)
      inhibited both the facilitatory effect of ET-1 and the anoxic contractions. At
      these concentrations BQ-123 caused a parallel shift to the right of the
      concentration-response curve to ET-1 and a small but significant depression of
      the response to norepinephrine, without affecting the maximal response to the
      catecholamine. BQ-123 did not significantly affect the concentration-response
      curve to Ca2+ in depolarizing solution (60 mM KCl). Monoclonal antibodies against
      ET-1 (70 micrograms/ml) inhibited the response to exogenous ET-1 and abolished
      the facilitating effect of the peptide, but did not affect the anoxic
      contractions. These results suggest that ET-1 contributes to anoxic contractions
      in canine coronary arteries without endothelium. The receptor involved belongs to
      the ETA-subtype and is not accessible to monoclonal antibodies.

PMID- 7509960
TI  - Characterization of endothelin isoforms in human heart: endothelin-2
      demonstrated.
AB  - In humans, three endothelin (ET) isoforms are predicted to exist by analysis of
      genomic DNA. However, evidence for the presence of all three mature ET peptides
      and their precursors remains unclear. Our aim was to identify the ET isoforms
      present in human heart, using radioimmunoassay (RIA) and reverse-phase high
      performance liquid chromatography (RP-HPLC). Antisera raised against the ET-1[15
      21] terminal sequence were specific for mature ETs, showing no cross-reactivity
      with their precursor pro-ETs. Antisera raised against the pro-ET-1[31-38]
      terminal sequence was specific for pro-ET-1, showing no cross-reactivity with
      other ET peptides. In extracts of human cardiac tissues, the concentrations of
      immunoreactive (IR) mature ET and pro-ET-1 were found to be as follows: left
      atrium (n = 3): 282.3 +/- 113.0, 21.9 +/- 11.0, respectively; right atrium (n =
      5): 308.3 +/- 95.4, 43.1 +/- 12.8, respectively; left ventricle (n = 6): 218.5 +/
      64.6, 47.9 +/- 11.9, respectively; right ventricle (n = 4): 215.1 +/- 79.8, 53.9
      +/- 13.0, respectively (fmol/g wet weight, mean +/- SEM, for total IR mature ET
      and pro-ET-1, respectively). RP-HPLC showed peaks of immunoreactivity that
      coeluted with authentic ET-1 in all extracts of human left atria and ventricle
      tested. In addition, peaks were also present corresponding to ET-2, ET-3, and pro
      ET-1. These results suggest that in addition to ET-1 and pro-ET-1, ET-2 and ET-3
      are present in the human heart.

PMID- 7509961
TI  - Endothelin-1 does not mediate acute hypoxic pulmonary vasoconstriction in the
      intact newborn lamb.
AB  - The mechanisms by which acute alveolar hypoxia induces pulmonary vasoconstriction
      remain unclear. Previous studies suggest that hypoxia-induced vasoconstriction is
      endothelium-dependent and is associated with the release of endothelin-1 (ET-1),
      a potent vasoactive paracrine hormone produced by vascular endothelial cells. The
      vasoconstrictive effects of ET-1 are likely to be mediated by ETA receptors
      located on vascular smooth-muscle cells. BQ-123 is a selective ETA receptor
      antagonist. To determine the role of ET-1 and ETA receptors on resting tone and
      hypoxic pulmonary vasoconstriction, we studied the effects of ET-1 and BQ-123 at
      rest and during hypoxia-induced pulmonary vasoconstriction in 12 intact newborn
      lambs (< 1 week old). At rest, the intrapulmonary infusion of BQ-123 did not
      change resting pulmonary arterial pressure but completely blocked the rapid
      increase in pulmonary artery pressure produced by high doses of ET-1 (2,000
      ng/kg) (23.0 +/- 10.8% versus -12.6 +/- 27.5%; p < 0.05). During mechanical
      ventilation there was no difference in the increase in mean pulmonary arterial
      pressure and pulmonary vascular resistance induced by alveolar hypoxia before and
      after BQ-123 (34.0 +/- 8.9% versus 30.5 +/- 10.9% and 25.3 +/- 11.6% versus 35.2
      +/- 22.4%). This study suggests that the pulmonary vasoconstrictive effects of ET
      1 are mediated by ETA receptors and that ET-1 does not mediate acute hypoxic
      pulmonary vasoconstriction in intact newborn lambs.

PMID- 7509962
TI  - Endothelin-1 may be a physiologic modulator of vasoconstriction in rat kidney.
AB  - The effect of endothelin-1 (ET-1), in concentrations well below threshold and
      near physiologic levels, has been examined on vasoconstrictor responses to
      perivascular nerve stimulation and norepinephrine in rat isolated kidney,
      perfused through the renal artery with physiologic salt solution. A 60-min
      exposure to ET-1 (1, 10, and 100 pM) had little or no effect on the basal
      perfusion pressure but enhanced responses to nerve stimulation (4 Hz, 10-s train)
      by 123 +/- 12% (n = 6), 125 +/- 8% (n = 6), and 226 +/- 49% (n = 7) of the
      control response, respectively. Responses to nerve stimulation were consistent in
      the absence of ET-1. Vasoconstrictor responses induced by norepinephrine (30-300
      pmol) increased with time in control experiments, but the increase was markedly
      greater in the presence of 10 and 100 pM ET-1. The vasoconstrictor responses
      caused by nerve stimulation and norepinephrine were greatly increased by the
      nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (NOLA, 100 microM). In
      the presence of NOLA, ET-1 (1 pM) enhanced the responses to nerve stimulation (1
      8 Hz, 10-s trains) by a significantly greater amount than in the absence of NOLA,
      suggesting that the enhancement by ET-1 is suppressed by NO release. The
      responses to norepinephrine (3-100 pmol) were also enhanced by 1 pM ET-1 in the
      presence of NOLA. The data suggest that ET-1 in physiologically relevant
      concentrations may have a role in the modulation of vascular reactivity in the
      renal circulation.

PMID- 7509963
TI  - Why big endothelin-1 lacks a vasodilator response.
AB  - The biphasic arterial blood pressure response to endothelin-1 (ET-1) results from
      a transient decrease, followed by a longer-lasting increase, in systemic vascular
      resistance. In contrast to ET-1, big endothelin-1 (bET-1) produces monophasic
      increases in systemic vascular resistance and arterial blood pressure. This is
      somewhat surprising, because bET-1 activity is reportedly due to ET-1, bET-1
      being converted to ET-1 by a putative converting enzyme. In this study we tested
      two hypotheses that could explain the singular effect of bET-1 on the arterial
      vasculature: that bET-1 vasoconstriction, mediated by ETA receptors at the level
      of the smooth muscle, masks the release of endothelial derived vasodilators,
      and/or that the endothelium develops tachyphylaxis owing to prolonged activation
      of endothelial ETB receptors. In anesthetized rats, blockade of the
      vasoconstrictor activity of bET-1 with BQ-123, an ETA-receptor antagonist, did
      not reveal a masked bET-1 vasodilator component in the rat hindquarter.
      Furthermore, in the presence of bET-1 (after 3.0 nmol/kg bET-1 i.v.), low doses
      of ET-1 (0.03-0.3 nmol/kg) produced dose-dependent hindquarter vasodilation,
      indicating activation of endothelial ETB and therefore no tachyphylaxis.
      Collectively, these experiments suggest that i.v. administration of bET-1 results
      in little or no activation of endothelial ETB receptors and therefore lacks a
      vasodilator response.

PMID- 7509965
TI  - Endothelins 1 and 3 and big endothelin-1 contract isolated human placental veins.
AB  - Experiments were designed to investigate the reactivity of vascular smooth muscle
      to endothelins (ETs) in veins taken from human placentas immediately after
      delivery. The placental veins were cut into rings and suspended between two
      stirrups in conventional organ chambers (filled with aerated, modified Krebs
      Ringer bicarbonate solution) for isometric recording of tension. ET-1 and ET-3
      caused concentration-dependent contractions of the isolated human placental
      veins. The responses induced by ET-1 were greater than those evoked by ET-3 and
      were not significantly affected by BQ-123, a selective inhibitor of ETA
      receptors. Contractions to big ET-1 were obtained in rings both with and without
      endothelium; they were inhibited by phosphoramidon, an inhibitor of endothelin
      converting enzyme. These findings indicate that the conversion of the precursor
      of ET-1 can occur in human placental veins. The receptors mediating the
      contraction of human placental veins to endothelins do not belong to the ETA
      subtype; the response to the peptides is probably mediated in part by an
      uncharacterized ET-receptor subtype and in part by ETB receptors. The output of
      big ET-1 in the vascular wall or from surrounding tissues in the placenta could
      be involved in the regulation of venous tone in this organ.

PMID- 7509964
TI  - Effect of endothelin-1 on canine airway blood flow.
AB  - The effect of endothelin-1 (ET-1) on the blood flow contributions of the
      pulmonary and systemic circulations to the trachea and main bronchi were measured
      in anesthetized dogs by injecting 15-microns radiolabeled microspheres into the
      right and left heart, respectively. After the microsphere injections the animals
      were killed, and the tracheal cartilage, tracheal muscle mucosa, and main bronchi
      were excised and collected for radioactive counting. The results of this study
      showed that under normal conditions tracheal blood flow was primarily systemic (>
      95% of total tracheal blood flow) averaging 25-50 ml/min/100 g, whereas both the
      pulmonary (9-10 ml/min/100 g) and systemic circulations (19-20 ml/min/100 g)
      contributed substantially to main bronchi blood flow. Administration of ET-1 i.v.
      decreased systemic tracheal cartilage blood flow from 25.3 +/- 3.8 to 14.5 +/-
      2.8 ml/min/100 g, systemic tracheal mucosal blood flow from 50.0 +/- 7.0 to 25.0
      +/- 7.0 ml/min/100 g, and systemic main bronchi blood flow from 19.4 +/- 4.6 to
      11.6 +/- 3.4 ml/min/100 g (p < 0.05). These results indicate that ET-1 is a
      potent constrictor of the airway circulation and may contribute to airway
      ischemia seen in different airway disease states.

PMID- 7509966
TI  - A new experimental model of epilepsy based on the intraventricular injection of
      endothelin.
AB  - Injection of endothelin-1 (ET-1, 9 pmol) into a lateral cerebral ventricle (LCV)
      of rats produces barrel-rolling and other convulsive signs that resemble those of
      generalized seizures in some types of epilepsy. Using the quantitative
      autoradiographic [14C]deoxyglucose technique, we documented that the
      neuroanatomical metabolic correlates of the ET-1-induced convulsions in rats are
      high rates of glucose utilization by structures near the site of LCV injection
      and throughout a diverse circuit of anatomically related brain regions. We
      speculate that this circuitry connects the caudate nucleus (putative site of
      initial stimulation in the forebrain) to the paramedian lobule and vermis of the
      caudal cerebellar cortex in the hindbrain. We evaluated the behavioral,
      physiological, and hypermetabolic responses to central ET-1 in the presence of
      three agents with anticonvulsant properties, providing clues about the cellular
      mechanisms of this convulsive and hypermetabolic state. Intraventricular MK-801
      [a noncompetitive antagonist of glutamic acid N-methyl-D-aspartate (NMDA)
      receptors], nimodipine (an antagonist of dihydropyridine-sensitive, voltage-gated
      calcium L-channels), or methylene blue (an inhibitor of guanylate cyclase, the
      enzyme on which nitric oxide acts) each produced significant attenuation of the
      behavioral and cerebral metabolic activation. The results introduce several
      quantitative parameters for an experimental model of employing intraventricular
      ET-1 in rats to study mechanisms of peptidergic convulsive disorders and the
      efficacies of promising anticonvulsant compounds in the treatment of epilepsy.

PMID- 7509968
TI  - Endothelin-1 and endotoxemia.
AB  - Sepsis leads to changes in blood volume and distribution. In the experiments
      reported here we monitored circulatory changes during endotoxemia and their
      relation to portal and systemic levels of endothelin-1 (ET-1). Piglets were
      monitored cardiovascularly under ketamine anesthesia for 6 h after an endotoxin
      infusion (saline controls). ET-1 levels in plasma were analyzed by RIA. In both
      portal and systemic blood a twofold increase in ET-1 levels was found after 1 h.
      This level remained significantly elevated for a further 3 h. This increase was
      concurrent with a drop in cardiac output, systemic vascular resistance, and blood
      pressure. In the portal circulation there was increased portal pressure and
      vascular resistance. There was no significant difference between the systemic and
      portal levels of ET-1.

PMID- 7509967
TI  - Endothelin in ectopic ACTH-secreting bronchial carcinoid tumors.
AB  - The presence of immunoreactive endothelin (ir-ET) in the tumor tissues of two
      cases of ectopic ACTH-secreting bronchial carcinoid tumors was studied by
      radioimmunoassay. The cross-reaction with big ET-1, ET-2, and ET-3 was 5%, 6%,
      and 6%, respectively. Tumor tissue ir-ET concentrations in two ectopic ACTH
      secreting bronchial carcinoid tumors were 920 and 3,370 fmol/g wet weight, which
      were much higher than those in pheochromocytomas (146 +/- 70 fmol/g wet weight; n
      = 12, mean +/- SD), adrenocortical tumors (115 +/- 105 fmol/g wet weight, n =
      14), and normal parts of adrenal glands (82 +/- 31 fmol/g wet weight, n = 12).
      High-performance liquid chromatography of the tumor tissue extract showed that
      the ir-ET was mainly eluted in the position of ET-1. Plasma levels of ir-ET in
      these two cases were not elevated (1.2 and 1.7 pmol/L). The findings of the
      present study suggest that ET-1 has local pathophysiologic roles in the tumor
      tissues of ectopic ACTH-secreting bronchial carcinoid tumors.

PMID- 7509969
TI  - Stimulation of endogenous endothelin release in the anesthetized rat.
AB  - Although many agents have been shown to stimulate release of endothelin (ET) in
      vitro, the factors regulating and affecting production and release of ET in
      intact animals remain obscure. Experiments were conducted to determine the effect
      of surgical preparation and infusion of plasma and/or saline on circulating
      immunoreactive (ir)-ET concentrations and to characterize the mechanism of
      endotoxin-induced increases in plasma ir-ET. Male Sprague-Dawley rats (210-325 g)
      anesthetized with Inactin were placed on a surgical heating table for a period of
      about 2 h before blood was collected via puncture of the abdominal aorta. The
      plasma concentration of ir-ET was 8.1 +/- 0.9 pg/ml in rats that did not undergo
      surgical preparation or receive any further treatment. Standard surgical
      preparation, as for renal clearance experiments (catheters in the trachea,
      femoral artery, femoral vein, and bladder), resulted in a dramatic rise in ir-ET
      to 17.7 +/- 3.0 pg/ml (p < 0.05). Infusion of plasma from donor rats (5 ml/kg
      over 20 min) resulted in an additional significant increase to 32.6 +/- 3.5 pg/ml
      (p < 0.05). In contrast, infusion of saline (0.9% NaCl) in a similar manner
      produced no further increase in ir-ET levels (23.2 +/- 3.2 pg/ml). Infusion of
      endotoxin in anesthetized, surgically prepared rats significantly increased ir
      ET. This increase was not blocked by a platelet-activating factor antagonist
      (Esai 6123), despite blockade of endotoxin-induced hypotension. Phosphoramidon,
      which has been shown to block in vivo conversion of exogenous big ET to ET, was
      unable to prevent endotoxin-induced increases in ir-ET.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7509970
TI  - Tissue contents of endothelin vary according to thyroid hormone status in rat.
AB  - Endothelin-1 (ET-1) is a 21-residue peptide isolated from the conditioned medium
      of cultured porcine endothelial cells and is widely distributed throughout the
      body, with relatively high levels in the kidney and lung. In this study we
      examined the influence of thyroid hormone status on immunoreactive endothelin (ir
      ET) levels in the plasma, lung, and kidney tissues of rats. Three weeks after
      surgical removal of the thyroid gland from male rats, the ir-ET levels in the
      lung and kidney were reduced by 39% and 42%, respectively. Similarly, ir-ET
      levels were decreased by 46% in the lung and 45% in the kidney of rats rendered
      hypothyroid by treatment with 0.1% (wt/wt) n-propylthiouracil (PTU) in the
      drinking water for 30 days. Replacement with daily L-thyroxine (T4) injections (5
      micrograms/100 g) prevented this decrease. However, thyrotoxicosis induced by
      daily L-T4 injections (10 micrograms/100 g) also caused a decrease of the lung ir
      ET levels by 49%, but had no significant effect on the renal ir-ET levels.
      However, the plasma ir-ET levels were similar in each group. Fast protein liquid
      chromatography study verified the presence of ir-ET-1 in the plasma and tissue
      extracts. This study demonstrates that thyroid hormone status affects tissue
      levels of ir-ET differently and that a euthyroid status is required for the
      maintenance of physiologic concentrations of ir-ET in the lung of male rats.

PMID- 7509971
TI  - Upregulation of renal endothelin receptors in glycerol-induced acute renal
      failure in the rat.
AB  - Acute renal failure was induced in rat with a hypertonic glycerol solution and
      endothelin-1 (ET-1) binding was measured in kidney membrane preparations. In
      control animals, [125I]-ET-1 bound to specific recognition sites in kidney cortex
      (Bmax = 134 +/- 11 fmol/mg protein) and medulla (Bmax = 300 +/- 9 fmol/mg
      protein) with an apparent dissociation constant (Kd) of 0.16 +/- 0.06 nM and 0.39
      +/- 0.07 nM for cortex and medulla, respectively. A single i.m. dose of 10 ml/kg
      glycerol (50% w/v) resulted in alterations of renal function that were maximal 48
      h after glycerol administration. After this 48-h period, serum urea was increased
      from 0.20 +/- 0.01 g/L to 1.16 +/- 0.20 g/L (p < 0.001) and creatinine clearance
      was reduced from 1.04 +/- 0.15 ml/min to 0.23 +/- 0.06 ml/min (p < 0.001). Renal
      ET-1 receptor density was significantly increased in glycerol-treated rats to 255
      +/- 14 fmol/mg protein in renal cortex (p < 0.01), and 576 +/- 55 fmol/mg protein
      in renal medulla (p < 0.01), with no significant modification of the Kd values.
      These results suggest that upregulation of ET-1 receptors is involved in renal
      hemodynamic impairment induced by glycerol.

PMID- 7509972
TI  - Elevated tissue endothelin content during focal cerebral ischemia in the rat.
AB  - To study the involvement of endogenous endothelin (ET) in the development of
      cerebral ischemia, we measured by radioimmunoassay brain tissue content of
      immunoreactive (ir)-ET-1 in a model of focal cerebral ischemia in the rat.
      Permanent occlusion of the middle cerebral artery (OMCA) was accompanied after 24
      h by a progressive but marked elevation of ir-ET-1 in the ipsilateral compared
      with the contralateral hemisphere (119% after 24 h; 184% after 48 h and 459%
      after 72 h). The pial vessels and the arteries of the circle of Willis did not
      respond with ir-ET-1 production. The increase in ir-ET-1 content in tissues was
      first observed in the caudate nucleus (after 24 h) and later in the cortex (after
      48 h), which was more variably injured. Transient ischemia followed by
      recirculation led to a slight increase of ir-ET-1, which also appeared after 24 h
      of recirculation. This study demonstrates that during permanent OMCA, the tissue
      content of ir-ET-1 markedly and progressively increases, whereas less severe
      ischemia (transient) is accompanied by a modest elevation of ir-ET-1 levels.
      These results suggest that endogenous ir-ET-1 production is involved in the
      development and the severity of ischemic injury.

PMID- 7509973
TI  - Stimulation of endothelin mRNA and secretion in human endothelial cells by FK
      506.
AB  - FK 506 is a powerful new immunosuppressant that is more effective in preventing
      and treating allograft rejection than cyclosporine (CyA). This study was
      undertaken to examine the effect of FK 506 on stimulation of endothelin-1 (ET-1)
      mRNA and secretion of ET-1 in human endothelial cells (EC) compared with the
      effects of CyA. The dose of 0.1 microM of CyA used in clinical practice induced
      expression of ET-1 mRNA and increased secretion of ET-1 in EC. The same dose of
      FK 506 had the same effect. A clinical dose of 0.01 microM of FK 506 did not
      induce expression of ET-1 mRNA and did not increase the secretion of ET-1 in EC.
      These findings suggest that the lower incidence of complications seen with FK 506
      is due in part to its use at a lower clinical dose compared with that of CyA.

PMID- 7509974
TI  - Endothelin is released from the porcine coronary circulation after short-term
      ischemia.
AB  - Endothelin (ET) is increased in plasma after myocardial infarction. Whether brief
      periods of myocardial ischemia not leading to myocardial infarction also increase
      plasma ET is not known. The purpose of the present study was to examine cardiac
      ET balance in association with a 10-min LAD occlusion followed by reperfusion.
      Venous blood was selectively sampled from the transiently ischemic myocardium
      using a shunt between the anterior interventricular vein and the right atrium in
      eight pentobarbital-anesthetized pigs. Flow in the shunt was measured with a
      Doppler flow probe. Arterial blood was drawn from the aortic arch. Plasma ET was
      measured using an ET [1-21]-specific 125I assay system. This assay system has no
      cross-reactivity with big ET. A net cardiac ET uptake of 0.7 (0.3-1.4) fmol min-1
      g-1 (median, 95% confidence interval) in the control period shifted to a net
      release during the first 10 min of reperfusion. The release reached a maximum of
      2.8 (0.4-6.0) fmol min-1 g-1 after 1.5 min of reperfusion. Cardiac venous ET
      concentration increased from 3.4 (2.5-4.8) to 4.4 (3.6-6.9) and 4.4 (3.6-6.6)
      fmol ml-1 at 1.5 and 5 min of reperfusion, respectively (p < 0.001 for both).
      Arterial ET concentration decreased from 4.8 (3.9-6.1) to 2.7 (2.4-4.3) fmol ml-1
      at 10 min of reperfusion (p < 0.001). ET is released from the porcine heart for
      several minutes during reperfusion after a brief coronary artery occlusion.

PMID- 7509976
TI  - Antihypertensive effects of the endothelin receptor antagonist BQ-123 in
      conscious spontaneously hypertensive rats.
AB  - Until recently, a role for endothelin-1 (ET-1) in the development and/or
      maintenance of hypertension has been based solely on indirect findings, e.g.,
      elevated circulating levels of peptide. However, with the development of specific
      ET-1 receptor antagonists it is now possible to examine this relationship
      directly. The present study describes the hemodynamic effects of systemic
      infusions of BQ-123, a selective endothelin (ETA)-receptor antagonist, in
      conscious, freely moving spontaneously hypertensive (SHRs) and normotensive
      Wistar-Kyoto (WKY) rats. Sustained infusions of BQ-123 (0.16-164 nmol/kg/min i.v.
      for 6 h) produced dose-dependent reductions in mean arterial pressure
      (approximately 30 mm Hg) in SHRs that were long-lasting (> 18 h) and reversible.
      Whereas cardiac output remained unaltered during BQ-123 infusion, the observed
      reduction in blood pressure was accompanied by a significant decrease (16%) in
      total peripheral resistance, indicating that the fall in blood pressure (an
      effect that was independent of the vehicle used and was not observed in WKY rats)
      was related primarily to peripheral vasodilation. Thus, the present study
      provides direct evidence showing that ET-1-receptor antagonists are effective
      antihypertensive (rather than hypotensive) agents and that endogenous ET-1 is
      involved in the pathophysiology of hypertension.

PMID- 7509977
TI  - Chronic pathophysiologic circulating endothelin levels produce hypertension in
      conscious dogs.
AB  - Although recent studies have reported endogenous plasma endothelin (ET) levels to
      be elevated two- to fivefold in chronic pathophysiologic states, whether such an
      increase in circulating ET levels alone can lead to significant long-term
      alterations in cardiovascular function is not known. The purpose of this study
      was to examine the long-term systemic hemodynamic effects of a pathophysiologic
      increase in circulating ET concentration in chronically instrumented, conscious
      dogs (n = 4). Infusion of endothelin (2.5 ng/kg/min) for 8 days increased plasma
      concentration of endothelin two- to threefold. ET increased mean arterial
      pressure from 85 +/- 3 to 103 +/- 3 mm Hg, which was sustained throughout the
      period of infusion. Total peripheral resistance was increased by approximately
      70%. Cardiac output decreased transiently by 25% and remained below control
      levels at the termination of ET infusion. These data indicate the importance of
      pathophysiologic levels of ET in controlling systemic hemodynamics in chronic
      conditions. Furthermore, ET may play a role as a mediator of chronic hypertension
      in pathophysiologic states associated with endothelial dysfunction.

PMID- 7509975
TI  - Venoconstriction to endothelin-1 in humans is attenuated by local generation of
      prostacyclin but not nitric oxide.
AB  - Endothelin-1 (ET-1) is known to be a potent and long-lasting constrictor of
      arteries and veins. We investigated whether local endothelial production of
      nitric oxide (NO) or prostacyclin modulates venoconstriction induced by the
      endothelium-derived peptide ET-1 in vivo in humans. Six healthy volunteers each
      received local dorsal hand vein infusion of ET-1 (5 pmol/min) for 60 min in five
      separate studies: once given alone; on three occasions co-infused with either the
      NO donor glyceryl trinitrate (GTN), the vasodilator prostaglandin, prostacyclin,
      or the inhibitor of nitric oxide synthase (NOS) NG-monomethyl-arginine (L-NMMA);
      and once given 30 min after oral administration of the irreversible inhibitor of
      cyclooxygenase, acetylsalicylic acid (aspirin). ET-1 alone caused slowly
      developing and long-lasting venoconstriction (maximal constriction 66 +/- 4%).
      Although GTN partially prevented ET-1-induced constriction (maximum 33 +/- 5%, p
      = 0.004 versus ET-1), inhibition of NOS did not affect ET-1-induced
      venoconstriction (maximum 55 +/- 4%). Prostacyclin was more effective at blocking
      the venoconstriction to ET-1 than GTN (maximum 12 +/- 3%, p = 0.0001) and there
      was substantial potentiation of ET-1-induced venoconstriction after pretreatment
      with aspirin (maximum 90 +/- 3%, p = 0.001). Despite the capacity of NO to
      attenuate responses to ET-1, L-NMMA did not potentiate ET-1-induced
      venoconstriction, suggesting little or no stimulated production of NO by ET-1 in
      human hand veins. However, substantial potentiation of ET-1-induced
      venoconstriction by aspirin indicates that endothelial production of prostacyclin
      modulates responses to ET-1 in human veins in vivo.

PMID- 7509980
TI  - Altered expression of ETB-receptor mRNA in the lung of rats with pulmonary
      hypertension.
AB  - To investigate the pathophysiologic role(s) of endothelin-1 (ET-1) in pulmonary
      hypertension, we studied the expression of ETB-receptor mRNA in the lung and
      venous plasma concentrations of ET-1 in rats with monocrotaline-induced pulmonary
      hypertension (PH). Three weeks after s.c. injection of monocrotaline (60 mg/kg),
      rats (PH rats, n = 6) were sacrificed. Vehicle-injected rats (n = 6) served as
      controls. The right ventricular systolic pressure of PH rats [58.0 +/- 4.7 mm Hg
      (mean +/- SEM)] was significantly higher than that in the vehicle-treated control
      rats (29.2 +/- 2.1; p < 0.01). Northern blot analysis showed that the expression
      of ETB-receptor mRNA decreased in the lung of PH rats. The venous plasma
      concentration of ET-1 measured by a sandwich-enzyme immunoassay was significantly
      higher in PH rats than in control rats (5.1 +/- 0.7 versus 1.3 +/- 0.2 pg/ml; p <
      0.01). The present findings suggest that the expression of ETB-receptor mRNA
      decreases in the lung of PH rats, which might be closely related to the increase
      in plasma ET-1 concentration in these rats.

PMID- 7509978
TI  - Endothelium-dependent contractions to endothelin in the rat aorta are mediated by
      thromboxane A2.
AB  - The present experiments were designed to determine the role of endothelium
      derived contracting factor(s) in the contractions of the rat aorta to endothelin
      1 (ET-1) and endothelin-3 (ET-3). Rings, with and without endothelium, of aortas
      of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY)
      rats were suspended in organ chambers for isometric tension recording in the
      presence of NG-nitro-L-arginine [NLA; inhibitor of nitric oxide synthase (NOS)].
      The removal of endothelium decreased the contractions evoked by both ETs in the
      aorta of the SHRs but not of the WKY rats. Indomethacin (inhibitor of
      cyclooxygenase), dazoxiben (inhibitor of thromboxane synthase), and SQ 29,548
      (antagonist of thromboxane A2 receptors) reduced the contractions to ETs in rings
      with, but not without, endothelium in the SHRs, whereas their effect was not
      endothelium dependent in the WKY rats. The presence of endothelium increased the
      basal and ET-stimulated release of thromboxane B2 in the aorta of the SHRs but
      not of WKY rats. These findings suggest that endothelium-derived thromboxane A2
      contributes to contractions evoked by ET-1 and ET-3 in the aorta of the SHRs but
      not of the WKY rats.

PMID- 7509979
TI  - Effect of endothelinA-receptor antagonist BQ-123 and phosphoramidon on cerebral
      vasospasm.
AB  - The present study was designed to determine whether an endothelinA (ETA)-receptor
      antagonist BQ-123 (cyclo[Dtrp, Dasp, pro-D-Val-Leu]) or an ET-converting enzyme
      inhibitor phosphoramidon may prevent development of cerebral vasospasm after
      subarachnoid hemorrhage (SAH). A "double hemorrhage" canine model of the disease
      was used (n = 17 dogs), and the degree of vasospasm of the basilar artery was
      assessed by angiography. Mongrel dogs of either sex were divided into three
      experimental groups: animals treated with daily intracisternal injections of BQ
      123 (10(-4) M; n = 6) or phosphoramidon (2 x 10(-4) M; n = 6) and control animals
      treated with saline solution (n = 5). Diameter of basilar arteries in animals
      treated with saline solution was reduced by SAH to 56 +/- 7% of control diameter.
      BQ-123 and phosphoramidon did not significantly affect SAH-induced vasospasm
      (diameters were 62 +/- 0% and 56 +/- 10% of control diameters for BQ-123 and
      phosphoramidon, respectively). In contrast, in isolated canine basilar arteries
      BQ-123 (10(-5) M) selectively inhibited concentration-dependent contractions to
      ET-1 (10(-11)-3 x 10(-8) M; n = 5). Levels of immunoreactive ET in plasma and
      cerebrospinal fluid were not affected by development of vasospasm. These results
      suggest that intracisternal injections of ETA-receptor antagonist or
      phosphoramidon cannot prevent SAH-induced cerebral vasospasm and that ET-1 may
      not be the major mediator responsible for the decrease in cerebral arterial
      diameter associated with SAH.

PMID- 7509981
TI  - Role of endogenous endothelin in extension of rabbit myocardial infarction.
AB  - The role of endogenous endothelin-1 (ET-1) in myocardial infarction was
      investigated in a rabbit ischemia-reperfusion model and in rabbit Langendorff
      hearts. AwETN40, a monoclonal antibody against ET-1, at 10 mg/kg i.v. inhibited
      hypertension and hypotension induced by ET-1 (0.3 nmol/kg i.v.): about 70-100%
      inhibition lasted for 24 h. In a coronary occlusion (30 min)-reperfusion (24 h)
      model, AwETN40 (10 mg/kg i.v.) reduced the infarct size from 60.9 +/- 4.6%
      (infarct region/ischemic region in weight, IgG1 kappa control; n = 5) to 37.1 +/-
      5.2% (n = 5, p < 0.05). Plasma ET-1 levels were increased significantly by
      coronary occlusion-reperfusion and returned to control level 24 h after
      reperfusion. Effects of ET-1 on the coronary vessels and cardiac contractility
      were studied in the Langendorff heart. ET-1 increased the perfusion pressure from
      concentrations as low as 10 pM, whereas the developed left ventricular pressure
      was not altered. These results suggest that ET-1 decreases oxygen supply to the
      cardiac muscles by constricting coronary vessels and that this, in turn, worsens
      the ischemic condition of the heart to extend the infarct size.

PMID- 7509982
TI  - COS-7 cells stably transfected to express the human ETB receptor provide a useful
      screen for endothelin receptor antagonists.
AB  - Endothelin acts via specific membrane-bound receptors through signal transduction
      pathways that include increases in intracellular free calcium and inositol
      triphosphate generation. Two endothelin receptors have been cloned. The ETA
      receptor is ET-1 selective, and the ETB receptor is isopeptide nonselective. Both
      receptor subtypes are widely distributed throughout the body, although ETA
      receptors predominate in vascular smooth muscle, whereas ETB receptors
      predominate in the brain. The presence of mixed receptor subtypes makes
      functional screening of subtype-specific analogues difficult. A eukaryotic
      expression vector was constructed by inserting the cloned coding region of the
      human ETB receptor downstream from the Rous sarcoma promoter. COS-7 cells were
      transfected with this construct, and cell lines were isolated with stably
      integrated copies of the relevant gene. One line, 1C7, was shown to specifically
      bind 125I-ET-1. Scatchard analysis indicated a Kd value of 8.8 pM and a Bmax
      value of 1.02 pM/mg. ET-1 stimulated phosphoinositide hydrolysis in a dose
      dependent manner, as did ET-3, sarafotoxin 6c, and [1,3,13,15Ala]ET-1, whereas
      BQ123, a selective ETA receptor antagonist, did not inhibit the action of ET-1.
      The transfected receptor stimulates phosphoinositide (PI) hydrolysis via a
      pertussis-sensitive pathway. Pretreatment of the membrane from 1C7 cells with
      dithio-bis-nitrobenzoic acid (DTNB) a negatively charged, nonpenetrating agent
      capable of oxidizing sulfhydryl groups, and N-ethyl-maleimide (NEM), a
      penetrating agent that causes irreversible alkylation of sulfhydryl groups,
      significantly reduces Bmax but has no effect on Kd. In whole cells, DTNB
      pretreatment abolishes the ability of ET-1 to stimulate PI hydrolysis.

PMID- 7509983
TI  - [125I]-endothelin-1 binding to vasa vasorum and regions of neovascularization in
      human and porcine blood vessels: a possible role for endothelin in intimal
      hyperplasia and atherosclerosis.
AB  - The distribution of [125I]-endothelin-1 (ET-1) binding sites on human and porcine
      vessels was studied with in vitro receptor autoradiography. Binding to normal
      human saphenous veins was compared to atheromatous veins used as coronary artery
      bypass grafts. Binding to porcine vessels, from an experimental model of intimal
      hyperplasia, was also studied. There was dense binding of [125I]-ET-1 to smooth
      muscle of all vessels examined, as well as to the vasa vasorum and regions of
      neovascularization of diseased vessels. Binding to microvasculature (vasa vasorum
      and regions of neovascularization) is of particular interest, because ET-1 has
      been shown to have mitogenic activity on vascular smooth-muscle cells in culture
      and microvessels are extremely sensitive to the constrictor effect of ET-1.
      Binding of [125I]-ET-1 to vasa vasorum of normal blood vessels and to regions of
      neovascularization of atheromatous vessels suggests that ET-1 plays a
      pathophysiologic role in atherosclerosis.

PMID- 7509984
TI  - Endothelin and vein bypass grafts in experimental atherosclerosis.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor whose serum concentration
      increases with the development of atherosclerosis. Coronary artery-vein bypass
      grafts are susceptible to vasospasm and to the development of accelerated
      atherosclerosis. Although ET-1 is thought to play a role in coronary vasospasm,
      the effect of ET-1 in atherosclerotic vein grafts is unknown. The responses of
      veins, arteries, and vein bypass grafts from normolipidemic and hyperlipidemic
      animals to ET-1 were therefore investigated. Vein bypass grafts were placed in
      the carotid position of 12 New Zealand White rabbits. Seven were fed a 1%
      cholesterol diet for 4 weeks before surgery and thereafter until harvest
      (hyperlipidemia), and five were fed a normal diet (normolipidemia). Vein grafts,
      contralateral common carotid arteries, and jugular veins were harvested 4 weeks
      after surgery. Whereas there were no histologic changes in veins or carotids,
      normolipidemic vein grafts developed intimal hyperplasia and hyperlipidemic vein
      grafts developed atherosclerosis. Isometric tension studies with ET-1 (10(-12) to
      10(-6) M) showed that hyperlipidemia increased the maximal tension generated to
      ET-1 in the veins (660 +/- 80 to 1,110 +/- 140 mg, mean +/- SEM; p < 0.05),
      carotids (150 +/- 30 mg to 540 +/- 120 mg; p < 0.05), and vein grafts (180 +/- 20
      to 450 +/- 60 mg; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509985
TI  - Age-dependent decrease in endothelium-dependent hyperpolarizations to endothelin
      3 in the rat mesenteric artery.
AB  - The present study was designed to investigate the effects of age on the
      endothelium-dependent hyperpolarizing effect of endothelin-3 (ET-3) in the
      mesenteric artery of the rat. Main superior mesenteric arteries, with endothelium
      of young (7-9 weeks), adult (20-24 weeks), and old (40-50 weeks) male Wistar
      Kyoto rats were studied. The cell membrane potential of the vascular smooth
      muscle cells was measured with glass microelectrodes in the presence of
      indomethacin (inhibitor of cyclooxygenase) and NG-nitro-L-arginine (NLA,
      inhibitor of nitric oxide synthase). In preparations with endothelium from young
      rats, ET-3 produced transient hyperpolarizations in a concentration-dependent
      (10(-8) to 10(-9) M) manner. In tissues from adult rats, only a small
      hyperpolarization to the peptide was observed at 10(-7) M, whereas no detectable
      membrane potential changes were observed in tissues from old animals. In tissues
      of all groups, acetylcholine produced concentration-dependent hyperpolarizations,
      the maximal amplitude of hyperpolarization was reduced in the old rats but no
      significant differences were observed in the threshold concentration for
      hyperpolarization to acetylcholine. These data suggest that aging decreases
      endothelium-dependent hyperpolarizations evoked by both ET-3 and acetylcholine.

PMID- 7509986
TI  - Effect of endothelin-1 infusion on the development of intimal hyperplasia after
      balloon catheter injury.
AB  - Previous studies have shown endothelin-1 (ET-1) to be mitogenic for smooth-muscle
      cells. We explored in vivo the ability of high ET-1 levels to worsen angioplasty
      restenosis. Left carotid artery balloon endothelial denudation was performed on
      14 rats. ET-1 was delivered via osmotic pump at a rate of 5 pmol/kg/min. Intimal
      development and plasma ET-1 levels were assessed at 2 weeks. Blood pressure and
      heart rate were measured throughout the study. For analysis, the animals were
      divided into three groups based on ET-1 levels at harvest: control, 4.3 +/- 0.5
      pmol/ml (n = 6); low ET-1, 5.2 +/- 0.9 pmol/ml (n = 4); and high ET-1, 23.1 +/-
      5.9 pmol/ml (n = 4). Although ET-1 infusion caused blood pressure elevation in
      both ET-1 groups, this was more marked and prolonged in the group with a high ET
      1 level at study conclusion. Evaluation of the intimal:medial area ratio showed a
      marked increase in intimal thickness in the high ET-1 group versus control (1.13
      +/- 0.23 versus 0.35 +/- 0.11; p < 0.05). We conclude that ET-1 infusion in
      responsive animals can cause worsening of the intimal hyperplastic response after
      mechanical injury. Further study is required to elucidate whether this is
      entirely caused by a direct effect of ET-1 on smooth-muscle cell mitogenesis or
      is also by the hemodynamic effects of ET-1-induced hypertension, or an effect of
      another mediator released in response to the ET-1 (e.g., angiotensin II).

PMID- 7509987
TI  - Hyperpermeability of abdominal capillary vessels to endothelin-1 in patients with
      diabetes mellitus.
AB  - To elucidate the pathophysiologic significance of circulating endothelin-1 (ET-1)
      to the vascular lesions in diabetic patients, ET-1 levels in plasma and
      peritoneal dialysis fluid were measured in 11 patients receiving continuous
      ambulatory peritoneal dialysis (CAPD) [five with diabetic nephropathy (group A);
      six with chronic renal failure without diabetes mellitus (group B)]. ET-1 levels
      were determined by a highly sensitive and specific enzymeimmunoassay. Plasma ET-1
      levels in group A were not significantly different from those in group B (3.3 +/-
      0.9 versus 3.5 +/- 0.9 pg/ml). However, the amounts of ET-1 in peritoneal
      dialysis fluid in group A were significantly greater than those in group B (19.2
      +/- 13.2 versus 10.4 +/- 6.3 ng/day). These results suggest that abdominal
      capillary vessels in diabetic patients are hyperpermeable to ET-1.

PMID- 7509988
TI  - Increased plasma endothelin-1 concentration in Kawasaki disease.
AB  - We compared the variation in plasma endothelin-1 (ET-1) levels by the sandwich
      enzyme RIA method during each of the clinical stages of Kawasaki disease, a
      systemic vasculitis occurring in children (30 cases, ages 4-62 months) and
      examined whether ET-1 could be a clinical parameter for predicting coronary
      artery dilatation. The results revealed that the ET-1 level in the acute stage
      was higher than that in the recovery stage, the chronic stage, or in healthy
      controls (3.46 +/- 1.22 versus 2.20 +/- 0.56, 1.55 +/- 0.52, and 1.57 +/- 0.45
      pg/ml, respectively; p < 0.01). Furthermore, in the acute stage the ET-1 level in
      the group with coronary artery dilatation (positive group, five cases) increased
      more than that in the negative group (25 cases) (5.13 +/- 1.64 versus 3.09 +/-
      0.70 pg/ml, respectively; p < 0.01). When the ET-1 value was more than 4.5 pg/ml
      in the acute stage, our prediction for coronary artery dilatation demonstrated a
      high value in indices of both sensitivity (100%) and specificity (96.1%). Thus,
      plasma concentration of ET-1 was increased in the acute stage of Kawasaki disease
      and was very high in patients with coronary artery dilatation. The plasma ET-1
      level was considered to be an important factor in predicting the dilatational
      lesions of the coronary artery in the acute stage of Kawasaki disease.

PMID- 7509990
TI  - Endothelin-1 promotes neointima formation after balloon angioplasty in the rat.
AB  - The long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA)
      is severely limited by the high incidence of vascular restenosis. Endothelin-1
      (ET-1) has been implicated in the pathogenesis of this response, since
      circulating levels of this potent smooth-muscle mitogen are elevated after PTCA.
      Therefore, this study examined the effect of exogenous ET-1 administration on the
      development of stenotic lesions in the rat common carotid artery angioplasty
      model. Immediately after left common carotid artery balloon angioplasty, rats
      received a 30-min i.a. infusion of either saline vehicle (0.9% NaCl w/v) or ET-1
      (17 pmol kg-1 min-1) via the left external carotid artery. Left and right common
      carotid arteries were removed 7 days later for quantitative image analysis.
      Balloon angioplasty caused significant neointima proliferation in left common
      carotid arteries, the extent of which was increased significantly by acute ET-1
      treatment (approximately 65% greater neointima formation relative to saline
      treated rats). ET-1 treatment had no effect on the geometry of contralateral
      right common carotid arteries. Therefore, these data support a role for ET-1 in
      the pathogenesis of vascular restenosis.

PMID- 7509989
TI  - Differential effects of endothelin-1 on normal and postischemic reperfused
      myocardium.
AB  - Using an isolated rat heart preparation and 31P magnetic resonance spectroscopy,
      we studied the effects of endothelin-1 (ET-1) and U-46619, a thromboxane-A2
      analogue, on coronary flow (CF), left ventricular developed pressure (LVP), and
      high-energy phosphate metabolism under control conditions (normal myocardium) and
      during postischemic reperfusion (reperfused myocardium). The selected doses of ET
      1 and U-46619 reduced CF in the normal myocardium to a similar extent (47.8 +/-
      1.5% and 48.7 +/- 4.6%, respectively). In contrast to ET-1, U-46619 induced a
      depression of LVP (20.2 +/- 6.9% versus 6.8 +/- 4.7%; p < 0.05) which was
      accompanied by an intracellular acidosis, indicating that a low-flow ischemia
      occurred. In reperfused hearts, the ET-1-induced decrease in CF was more
      pronounced compared to U-46619 (79.5 +/- 1.6% versus 59.0 +/- 5.9%; p < 0.05) and
      to ET-1-induced decrease in CF in the normal myocardium (74.0 +/- 7.9% versus
      32.4 +/- 6.3%; p < 0.05). This was accompanied by a large decrease in LVP and in
      levels of high-energy phosphate compounds. Therefore, the effects of ET-1 but not
      of U-46619 are enhanced in reperfused hearts. This may contribute to the delayed
      recovery of the postischemic reperfused myocardium.

PMID- 7509991
TI  - Theoretical conformational analyses of endothelin-1 in vacuum, aqueous, and lipid
      environments.
AB  - Endothelin-1 (ET-1) is a flexible molecule capable of existing in multiple shapes
      (conformations) depending on the surrounding molecular solvation. The
      conformational diversity of ET-1 was studied in three solvation spheres (gas
      phase, aqueous, and membrane lipid) with the new evolving biotechnology of
      computational biomolecular simulation. Simulations were performed using a
      combination of molecular mechanics, molecular dynamics, and semiempirical quantum
      mechanics calculations in a RISC architecture large-scale computing environment.
      Marked differences between the gas phase "folded" conformation and the membrane
      lipid "extended" conformation were identified.

PMID- 7509993
TI  - Regulation of endothelin-1 expression in normal and transfected endothelial
      cells.
AB  - Calcium phosphate precipitation and retrovirus-mediated infection methods were
      used to stably infect bovine pulmonary artery endothelial cells (BPAECs) with
      mammalian expression vectors bearing human prepro-ET-1 cDNA. The calcium
      phosphate precipitation method afforded a stably transfected cell line that
      expressed approximately four times higher ET-1 than untransfected BPAEC by
      radioimmunoassay and at the mRNA level. The retrovirus-mediated transfection
      method yielded stably infected clones that secreted eightfold to 10-fold higher
      ET-1 than the nontransfected BPAECs; one clone continued to produce 10-fold
      higher levels after continuous assay for 1 year. Both transfected and
      nontransfected cells showed an increase (approximately twofold) in ET-1
      production in response to thrombin (10 U/ml). Downregulation of ET-1 production
      was exhibited by both transfected and nontransfected cells in response to nitric
      oxide (NO) donors: sodium nitroprusside (NOPr), S-nitroso-N-acetoxy penicillamine
      (SNAP), and acetoxime. The potentiation of NO by superoxide dismutase (SOD) also
      downregulated ET-1 production. These studies show that an exogenous gene
      introduced into a cell type that normally expresses that gene product can be
      regulated by agonists and antagonists in a manner similar to the normal gene
      regulatory mechanisms for that cell type. This is of potential importance in gene
      therapy experiments, where mechanisms for regulation of expression remain
      elusive.

PMID- 7509992
TI  - In vivo pharmacology of Ro 46-2005, the first synthetic nonpeptide endothelin
      receptor antagonist: implications for endothelin physiology.
AB  - Ro 46-2005 is a small-molecular-weight nonpeptide antagonist of the endothelin
      (ET), ETA and ETB receptors, chemically derived from a class of compounds
      identified by systematic screening of chemicals. In vivo, Ro 46-2005 inhibited
      the depressor and, only at high doses (100 mg/kg i.v.) the pressor effect of ET
      1. However, much lower doses (1 to 10 mg/kg i.v.) were sufficient to inhibit the
      pressor effect of the precursor big ET-1. As intravenous big ET-1 injection
      potentially reproduces better than ET-1 injection the physiological pattern of
      release of ET-1, we propose that intravenous big ET-1 should be used to evaluate
      the effects of antagonists on the constricting endothelin receptors.

PMID- 7509994
TI  - Extracellular cysteine residues 174 and 255 are essential for active expression
      of human endothelin receptor ETB in Escherichia coli.
AB  - The coding sequences for the non-isopeptide-selective human endothelin receptor
      ETB were introduced into the prokaryotic expression vector pKK233-2, and the
      resulting construct was used for transformation of competent E. coli JM105 cells.
      Specific binding was observed for bacterial membrane fractions, using labeled ET
      1 as a ligand. Site-directed mutagenesis was employed to individually modify the
      triplets for the cysteines of the first and second extracellular loops of ETB to
      alanine codons. E. coli JM105 transformed with the mutated plasmids no longer
      displayed specific ET-1 binding to membranes, which suggests a crucial role for
      these extracellular cysteines in agonist binding or receptor stability.

PMID- 7509995
TI  - Calcium ionophores inhibit the release of endothelin-1 from endothelial cells.
AB  - We have determined the effect on endothelin-1 (ET-1) release of stimulating
      cultured endothelial cells for 24 h with Ca2+ ionophores. The results obtained
      using cultured bovine aortic endothelial cells (BAECs) were compared with those
      using the human endothelial cell line (EA.hy 926). ET-1 was measured using a
      radioimmunoassay specific for the C-terminal ET[16-21] sequence. Ionomycin (1
      microM) lessened ET-1 accumulation over 24 h in the conditioned medium from BAECs
      (-37%) and EA.hy 926 (-25%). A23187 was a more potent inhibitor of ET-1 release.
      With BAECs, ET-1 release was inhibited by 28% and 77% at 0.1 microM and 1 microM
      A23187, respectively. The corresponding decreases for EA.hy 926 were 20% and 98%.
      A23187 at 0.2 microM lowered ET-1 concentrations in the medium after 24 h by 44%
      and 24% for BAECs and EA.hy 926, respectively. Neither NG-monomethyl-L-arginine
      (0.2 mM) nor indomethacin (10 microM), either alone or in combination, affected
      the inhibition by A23187. Thus, this inhibitory effect is not dependent on the
      stimulation of nitric oxide or prostacyclin synthesis. Additional factors in
      endothelial cells, activated by elevated Ca2+ levels, may be important in
      exerting an inhibitory influence on ET-1 formation.

PMID- 7509996
TI  - Effect of heparin on endothelin-1 production by cultured human endothelial cells.
AB  - Heparin shows a blood pressure-lowering effect in various hypertensive rat
      models. This study was designed to examine the effect of heparin on
      vasoconstrictor endothelin-1 (ET-1) production by cultured human umbilical vein
      endothelial cells (HUVECs). ET-1 and cyclic GMP levels in the medium were
      determined by radioimmunoassay. ET-1 mRNA was quantified by densitometric
      Northern blot analysis. ET-1 was released into the medium in a time-dependent
      manner, and its release was augmented by thrombin (10 U/ml). Heparin suppressed
      both basal and thrombin-stimulated ET-1 secretion and its mRNA expression in a
      dose-dependent manner. Heparin suppressed ET-1 mRNA expression in a time
      dependent fashion. Heparin did not suppress both basal and thrombin-stimulated ET
      1 production in the presence of NG-monomethyl-L-arginine (L-NMMA) (10(-5) M). The
      production of cGMP stimulated by thrombin was significantly enhanced by heparin,
      but not in the presence of L-NMMA (10(-5) M). Heparin may suppress
      vasoconstrictor ET-1 production mediated by the enhancement of endothelium
      derived nitric oxide in HUVECs.

PMID- 7509997
TI  - Heparin inhibits endothelin-1 and proto-oncogene c-fos gene expression in
      cultured bovine endothelial cells.
AB  - We studied the inhibitory effects of heparin, thrombin inhibitor, and protein
      kinase C (PKC) inhibitor on basal and thrombin-induced preproendothelin-1 (prepro
      ET-1) and proto-oncogene c-fos mRNA expression in cultured bovine endothelial
      cells (ECs). Northern blot analysis using cDNA for bovine prepro-ET-1 as a probe
      showed that heparin lowered not only the basal but also the stimulated expression
      of prepro-ET-1 mRNA by thrombin. A selective thrombin inhibitor (argatroban) and
      a PKC inhibitor (staurosporine) also inhibited thrombin-induced but not basal
      prepro-ET-1 mRNA expression. Heparin similarly inhibited thrombin-induced c-fos
      proto-oncogene mRNA expression in ECs. These data suggest that heparin, in
      addition to its antithrombin effect, has an inhibitory effect on prepro-ET-1 mRNA
      expression, possibly via a PKC-dependent pathway.

PMID- 7509999
TI  - Evidence for vesicles that transport endothelin-1 in bovine aortic endothelial
      cells.
AB  - To facilitate studies of the intracellular processing of endothelin-1 (ET-1) in
      endothelial cells we developed an enrichment procedure for the isolation of
      transport or secretory vesicles containing ET-1. Cultured bovine aortic
      endothelial cells (BAECs) were disrupted using a tight-fitting Dounce
      homogenizer, and subcellular fractions were isolated by sucrose-density-gradient
      ultracentrifugation. ET-1 immunoreactivity (ET-IR) in the fractions was measured
      with a specific ET[16-21] radio-immunoassay (RIA). The major peak of ET-IR was
      consistently localized at the 1.0/1.2 M sucrose interface (10.96 fmol/10(6)
      cells) in each preparation of subcellular fractions. The mean level of ET-IR at
      this interface, expressed as a percentage of the total, was 47.9 +/- 3.5% (n =
      6). This finding provides strong evidence for the existence of a vesicle that
      transports ET-1 within BAECs, which may be an important site for endogenous ET-1
      processing. A number of studies have reported that the final processing step in
      ET-1 biosynthesis by the hypothetical endothelin-converting enzyme (ECE) is
      inhibited by phosphoramidon (PHOS). Therefore, levels of PHOS-sensitive ECE
      activity in each fraction were assessed in parallel with ET-IR levels. The ECE
      activity associated with the peak of ET-IR (2.67 pmol ET-1/h/10(6) cells) was
      insensitive to 100 microM PHOS. However, the peak of ECE-like activity (10.4 pmol
      ET-1/h/10(6) cells) localized in the 0.8 M sucrose band was inhibited by 79% in
      the presence of 100 microM PHOS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7509998
TI  - Intracellular localization of membrane-bound endothelin-converting enzyme from
      rat lung.
AB  - Intracellular localization of membrane-bound endothelin-converting enzyme (ECE)
      was examined in rat lung by sucrose-gradient ultracentrifugation coupled with
      organelle marker studies. Lung microsomal fraction was prepared and fractionated
      by ultracentrifugation through a linear sucrose gradient. Sedimentation profiles
      of marker enzymes for plasma membrane, Golgi, lysosome, and mitochondria showed
      that these organelles were measurably separated from each other. A major portion
      of phosphoramidon-sensitive ECE activity was distributed with a single peak at
      the approximately 1.05-1.2 M sucrose region, where it appeared to be cosedimented
      with membrane vesicles that contained the two different marker enzymes for Golgi
      apparatus. These microsomal vesicles also seemed to contain the majority of
      endogenous immunoreactive ET-1 found in the lung. These findings suggest that a
      majority of the ECE activity in rat lung may be responsible for the intracellular
      conversion of big ET-1 during its transit through the secretory pathways.

PMID- 7510000
TI  - Endothelin-2-converting enzyme from human renal adenocarcinoma cells is a
      phosphoramidon-sensitive, membrane-bound metalloprotease.
AB  - From the membrane fraction of cultured human renal adenocarcinoma (ACHN) cells,
      two endothelin-2-converting enzymes (ECE-2A and ECE-2B) were solubilized with
      detergent Lubrol PX and separated by hydrophobic butyl fast-performance liquid
      chromatography. The pH range of the converting activity of ECE-2B for big
      endothelin-1 (big ET-1), big ET-2, or big ET-3, was very narrow, and the optimal
      pH for each substrate was significantly different; the pH optimum for big ET-1
      was 6.8 and that for big ET-2 or big ET-3 was 6.4. The ET-converting activity was
      abolished by phosphoramidon, 1,10-phenanthroline and EDTA but was not inhibited
      by thiorphan, E-64, leupeptin, PCMS, p-APMSF, or pepstatin A. The conversion
      efficiency for big ET-2 or big ET-3 by ECE-2B was approximately one-eighth of
      that for big ET-1. The molecular weight of ECE-2B was estimated to be 400 kDa by
      gel filtration. Because these characteristics of ECE-2B are very similar to those
      of ET-1-converting enzyme (ECE-1) in endothelial cells, these results raise the
      possibility that ECE-2B is identical to ECE-1 and that a single ECE
      physiologically converts all big ETs to the corresponding ETs in ET-producing
      cells.

PMID- 7510001
TI  - The metabolism of endothelin-1 and big endothelin-1 by the isolated perfused
      kidney of the rabbit.
AB  - The activity of human big endothelin-1 (bET-1) or endothelin-1 (ET-1) was
      investigated in the isolated perfused kidney of the rabbit. In some experiments
      the effluent superfused a rabbit jugular vein (RbJV) or rat colon (RC), and bolus
      doses of bET-1 or ET-1 were administered either directly over the tissue (OT) or
      through the kidney (TK). When injected OT, the contractile responses of the RbJV
      to ET-1 were > or = 100-200 times more than those to bET-1. However, at least 10
      times the ET-1 dose given OT was needed TK to produce an equivalent contraction
      of the RbJV, showing that ET-1 was being inactivated or removed by the kidney.
      Injections of bET-1 TK produced increases in perfusion pressure of a magnitude
      1/25th of those of ET-1. In some experiments administration of bET-1 TK was
      associated with the release into the perfusate of an ET-1-like factor that
      contracted the RbJV, but not the RC (used to detect any angiotensin II release),
      at doses that had little effect when administered OT, suggesting that bET-1 was
      being activated by the kidney. Phosphoramidon (10 microM) infused TK blocked (92
      +/- 1% inhibition) the renal responses to bET-1 and reduced the overflow of ET-1
      like material onto the tissues without affecting ET-1-induced renal
      vasoconstriction. Incubation of bET-1 with rabbit renal cortical microsomes (100
      micrograms protein) resulted in the generation of ET-1-like activity, as assessed
      by bioassay, which was inhibited by phosphoramidon (10 microM).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7510002
TI  - Rapid inactivation of endothelin-1 by a carboxypeptidase-like enzyme purified
      from rat kidney.
AB  - A survey of various rat tissues showed that the kidney had the highest endothelin
      degradation enzyme activity. An enzyme that effectively inactivated endothelin-1
      was purified from soluble kidney extracts. This enzyme appeared to contain two
      subunits with molecular weights of 34 kDa and 21 kDa. It displayed
      carboxypeptidase-like properties and cleaved off the carboxyl terminal tryptophan
      of endothelin-1. These results agree with the findings that endothelin-1 is
      cleared efficiently by the kidney and suggest that this enzyme plays a role in
      the homeostasis of circulating endothelin-1.

PMID- 7510003
TI  - Presence of furin mRNA in cultured bovine endothelial cells and possible
      involvement of furin in the processing of the endothelin precursor.
AB  - Recently it was documented that furin, a calcium-dependent serine endoprotease,
      cleaves many protein precursors at pairs of basic amino acids, thus liberating
      the biologically active peptides. The endothelin precursors follow a biosynthetic
      pathway similar to these proteins, where the precursor is initially processed to
      the intermediate, big endothelin (big ET) before its conversion to the endothelin
      (ET) peptide. Analysis of the amino acid sequence of the endothelin pro-proteins
      shows that they are susceptible to processing by endoproteases that cleave at
      pairs of basic amino acids. For example, human endothelin-1 (ET-1) precursor
      possesses a typical furin cleavage site motif (Arg-X-Lys/Arg-Arg) at the
      following residues: Arg32-Ser33-Lys34-Arg35 and Arg72-Ser73-Lys74-Arg75. We have
      isolated mRNA from cultured bovine endothelial cells and, using a human furin
      cRNA probe, shown that a furin mRNA of 4.5 kb is present in these cells. We
      propose that furin, a novel endoprotease belonging to the mammalian subtilisin
      family of serine proteases, may be implicated in the processing of pro-endothelin
      precursors, liberating big ET.

PMID- 7510004
TI  - Effects of phosphoramidon in endothelial cell cultures on the endogenous
      synthesis of endothelin-1 and on conversion of exogenous big endothelin-1 to
      endothelin-1.
AB  - Several studies have shown that phosphoramidon (PHOS) reduces the release of
      endothelin-1 (ET-1) from cultured endothelial cells. Moreover, the main
      endothelin-converting enzyme (ECE) activity in these cells is a membrane-bound
      metallopeptidase that is also inhibited by PHOS. We have investigated further the
      role of the PHOS-sensitive ECE in the conversion of big ET-1 to ET-1. ET-1 was
      measured using a radioimmunoassay specific for the C-terminal ET[16-21] sequence.
      The effect of PHOS on the production of ET-1 from endogenous precursors was
      determined using cultured bovine aortic endothelial cells (BAECs) and the human
      endothelial cell line (EA.hy 926). The concentrations of ET-1 accumulating in the
      medium over 24 h from BAECs were lowered by PHOS (-27% 10 microM, -76% 100
      microM). In contrast, with EA.hy 926 cells, the same concentrations of PHOS
      increased by five- to sixfold the amount of ET-1 present in the medium after 24-h
      incubation. In other experiments, incubation of big ET-1 (1 microM) with intact
      BAECs or EA.hy 926 cells resulted in the generation of ET-1, and with both cell
      types this was inhibited by PHOS (IC50: BAECs = 6.4 microM; EA.hy 926 = 0.26
      microM). These results are consistent with both cell types having a PHOS
      sensitive ECE that is readily accessible to exogenous big ET-1 and is therefore
      probably located on the plasma membrane. Furthermore, another intracellular ECE
      may play a part in the endogenous intracellular formation of ET-1 in EA.hy 926
      cells.

PMID- 7510005
TI  - Prolonged treatment by phosphoramidon modulates the number of endothelin
      receptors in cultured Swiss 3T3 fibroblasts.
AB  - Endothelin (ET) is generated from prepro-ET initially by dibasic pair
      proteolysis, followed by a specific proteolytic cleavage between Trp21 and Val22.
      Currently, intense research is focused on the investigation of a metalloprotease
      that is inhibited by phosphoramidon (PHOS) only, but not by other protease
      inhibitors. In this report, we show that ET binding was increased significantly
      in cultured Swiss 3T3 fibroblasts with PHOS pretreatment. The effect of PHOS was
      dose- and time-dependent. Other protease inhibitors, such as thiorphan, pepstatin
      A, E-64, phenylmethyl sulfonyl fluoride, and aprotinin, failed to exert a similar
      effect. Control experiments indicated that the effect of PHOS was not due to
      inhibition of 125I-ET-1 degradation. Binding studies using whole cells or
      membranes prepared from cell show that ET binding sites increased from 23,000 to
      133,000 sites/cell in control versus PHOS-treated cells. The effect of PHOS
      treatment on the ET receptor may be due to the inhibition of a protease
      responsible for ET-receptor processing. This effect is likely to complicate
      interpretation of results from studies using PHOS to block the putative ET
      converting enzyme.

PMID- 7510006
TI  - Phosphoramidon inhibits the conversion of big ET-1 into ET-1 in the pithed rat
      and in isolated perfused rat kidneys.
AB  - Endothelin-1 (ET-1) is a powerful renal vasoconstrictor peptide that could be
      implicated in acute renal failure. The aim of this study was to test the effects
      of the endothelin-converting enzyme (ECE) inhibitor phosphoramidon on pressor
      responses to ET-1 and its precursor, big ET-1, in isolated perfused rat kidneys
      and in pithed rats. In Tyrode-perfused rat kidneys, both big ET-1 (0.2-0.4 nmol)
      and ET-1 (0.01-0.03 nmol) evoked dose-dependent constrictions. Phosphoramidon (10
      microM) selectively inhibited the pressor responses to big ET-1 without altering
      those to ET-1, norepinephrine, angiotensin I (AT-I), or angiotensin II (AT-II).
      The metalloprotease inhibitor thiorphan, but not the angiotensin-converting
      enzyme (ACE) inhibitor perindoprilate, also selectively inhibited the renal
      constrictions caused by big ET-1 but not those induced by ET-1. In vivo, both big
      ET-1 and ET-1 (0.5-2 nmol/kg) evoked pressor responses that were augmented by
      indomethacin (15 mg/kg) and L-NNA (1 mg/kg/min). Phosphoramidon selectively
      inhibited the pressor responses to big ET-1 (ID50: 78 micrograms/kg/min) without
      affecting those to ET-1, AT-I, or AT-II. These data illustrate that the pressor
      responses to big ET-1 in the rat, both in vivo and in vitro, are due to its
      conversion into ET-1 by a phosphoramidon-sensitive ECE. In the rat,
      phosphoramidon selectively inhibits ECE but not ACE both in vitro and in vivo.

PMID- 7510007
TI  - Pharmacologic evidence for the specificity of the phosphoramidon-sensitive
      endothelin-converting enzyme for big endothelin-1.
AB  - The pharmacology of human big endothelin-1 (big ET-1) and big ET-3 was compared
      in five pharmacologic models: perfused rat and guinea pig lungs, perfused rabbit
      kidney, and in the rat and the guinea pig in vivo (blood pressure monitoring). In
      these models, big ET-1 consistently induced concentration- or dose-dependent
      pharmacologic effects sensitive to phosphoramidon (vasopressor or prostanoid
      releasing effects). In contrast, big ET-3, dissolved in either phosphate-buffered
      saline (pH 7.4) or 0.1% acetic acid, was inactive in all the models used in this
      study. In addition, the activity of big ET-3 was also assessed in the prostatic
      portion of the rat vas deferens. In this model, although big ET-1 induced a
      phosphoramidon-sensitive increase of the twitch response of the tissue to
      electrical stimulation, big ET-3, dissolved either in phosphate-buffered saline
      or acetic acid, remained inactive. Our results, presented in the above-mentioned
      models, illustrate the capacity of the phosphoramidon-sensitive endothelin
      converting enzyme (ECE) to discriminate between human big ET-1 and big ET-3.

PMID- 7510008
TI  - Processing and metabolism of endothelin peptides by porcine lung membranes.
AB  - The processing and metabolism of big endothelin-1 (big ET-1) and endothelin-1 (ET
      1) by a membrane fraction from pig lung was examined. The principal activity in
      this membrane fraction hydrolyzing ET-1 was identified as endopeptidase-24.11 (EC
      3.4.24.11) by inhibitory and immunological criteria. More than 90% of this
      endopeptidase-24.11 activity could be removed by immunoadsorption. ET-converting
      activity was partially purified from the solubilized membrane fraction by lectin
      chromatography on a Ricinus communis agglutinin-120-agarose column followed by
      immunodepletion of endopeptidase-24.11. The production of the C-terminal fragment
      of big ET-1 could be detected in this partially purified preparation and was
      inhibited by phosphoramidon (10 microM) but not by thiorphan (10 microM). The
      fluorogenic substrate succinyl-Ile-Ile-Trp-7-amido-4-methylcoumarin was
      hydrolyzed by pig lung membranes, but this activity was insensitive to
      phosphoramidon, suggesting that neither endopeptidase-24.11 nor endothelin
      converting enzyme hydrolyze this substrate. Purified endopeptidase-24.11 also
      failed to hydrolyze the fluorogenic peptide.

PMID- 7510009
TI  - In vitro and in vivo studies with a series of hexapeptide endothelin antagonists.
AB  - The effects of different amino acids incorporated into the 16 and 17 positions of
      the C-terminal hexapeptide of ET-1 were examined. Structure-activity
      relationships (SAR) of the ET receptor antagonists PD 142893 [Ac-(D-Dip16-L-Leu17
      L-Asp-L-Ile-L-Ile-L-Trp) (D-Dip = 3,3-D-diphenylalanine)] and PD 145065 [Ac-(D
      Bhg16-L-Leu17-L-Asp-L-Ile-L-Ile-L-Trp) (D-Bhg = 5H-dibenzyl[a,d]cycloheptene
      10,11-dihydro-glycine)] uncovered certain requirements for high potency. The
      disodium salt of PD 145065 has 4.0 and 15 nM binding affinity (IC50 values) for
      the ETA (rabbit renal artery vascular smooth-muscle cells) and ETB receptor (rat
      cerebellum), respectively. The compound is also an antagonist of ET-1- and SRTX
      6c-stimulated vasoconstrictor activity, with pA2 values of 6.9 (rabbit femoral
      artery, ETA assay) and 7.1 (rabbit pulmonary artery, ETB assay). The tripeptidic
      ETA antagonist FR 139317 was found to be less active in the rabbit femoral
      artery, with a pA2 value of 6.0, and inactive in the rabbit pulmonary artery.
      Substitution of acidic and basic residues at position 17 in PD 142893 and PD
      145065 indicates differences in selectivity. Incorporation of bulky non-natural
      amino acids at position 16 has led to potent nonselective analogues, including Ac
      D-Bheg16-L-Leu-L-Asp-L-Ile-L-Ile-L-Trp [D-Bheg (5H-dibenzo[a,d]cycloheptene
      glycine)]. The in vivo effects of single-bolus doses of selected ET antagonists
      on depressor and pressor responses to ET-1 in anesthetized ganglion-blocked rats
      were evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510010
TI  - Enzyme-histochemical staining of dermal lymphatic capillaries by guanylate
      cyclase.
AB  - Human foreskins were examined for enzyme-histochemical staining of microvessels
      using guanylate cyclase, an enzyme similar to adenylate cyclase. Like 5'
      nucleotidase (which hydrolyzes 5'-adenosine monophosphate to adenosine), and
      adenylate cyclase (which converts adenosine triphosphate to cyclic AMP),
      guanylate cyclase selectively stains positive for lymphatic capillaries and
      therefore may be another useful histochemical marker to differentiate dermal
      lymph from blood capillaries.

PMID- 7510011
TI  - Heparin potentiation of the effect of acidic fibroblast growth factor on
      astrocytes and neurons.
AB  - Acidic fibroblast growth factor (aFGF) could stimulate the proliferation of
      astrocytes and promote the survival of neurons from newborn rat brain in vitro.
      The effects of aFGF on both astrocytes and neurons were significantly potentiated
      by heparin. The effect of aFGF (2 ng/ml) with heparin (10 mu g/ml) on the
      survival of neurons was a hundredfold more potent than that of aFGF (200 ng/ml)
      without heparin.

PMID- 7510012
TI  - Successful islet allotransplantation in diabetic rats immunosuppressed with
      FK506: a functional and immunological study.
AB  - The effect of a novel immunosuppressive agent, FK506, on fresh islet allografts
      was evaluated in diabetic rats across major histocompatibility complex (MHC)
      barriers with respect to the transplantation (TR) site, islet source, treatment
      regimen, and antidonor antibody (Ab) titers of the recipients after TR. The
      functional periods of Wistar (Wi) islets transplanted under kidney capsule (KC)
      or intraportally (IPo) and of a mixture of Wi and Lewis (Le) islets under KC or
      IPo in nonimmunosuppressed ACI rat recipients were 6.9 +/- 0.4 (n = 7), 6.4 +/-
      0.5 (n = 7), 5.6 +/- 0.4 (n = 7), and 6.2 +/- 0.4 (n = 5) days, respectively.
      FK506 treatment at 1 mg/kg/d intramuscularly (IM) for 2 weeks (protocol I)
      following islet TR under KC and IPo significantly prolonged the allograft
      function to more than 71.8 +/- 11.3 (n = 10) and 161.7 +/- 18.6 (n = 11) days,
      respectively. Additional treatment with FK506 at 1 mg/kg/wk (protocol II) further
      increased the islet survival under KC to more than 212.6 +/- 22.3 (n = 8) days.
      With this FK506 treatment protocol, the Wi + Le mixed-islet allograft function
      was extended to more than 106.1 +/- 10.5 (n = 7) and 167.9 +/- 28.6 (n = 7) days
      under KC and IPo, respectively. Nephrectomy in 8/8 ACI rats with long-term
      functioning Wi (n = 6) and Wi + Le (n = 2) islet allografts resulted in their
      return to hyperglycemia. Immunohistochemical staining showed abundant insulin
      positive cells at the graft site, with small numbers of CD4- and CD8-positive
      cells present in the vicinity of the normal-appearing islets. Macrophages were
      not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510013
TI  - Experimental antiangiogenesis therapy using cortisone acetate in murine bladder
      cancer: independence from "tumor volume effect".

PMID- 7510016
TI  - [Studies on leakage of pancreatic juice following distal pancreatectomy from the
      standpoint of transition of amylase and trypsin values in exudate].
AB  - Selective drainage method of remnant pancreatic stump (RPS) using latex rubber
      was devised, and I have obtained a good clinical result for the prevention of
      postoperative bleeding due to the leakage of pancreatic juice after distal
      pancreatectomy. In this study, amylase (Am:IU/L) and trypsin (Tr:ng/ml) values in
      exudate were measured to clarify the actual leakage of pancreatic juice. Thirty
      three patients with gastric cancer who underwent total gastrectomy with distal
      pancreatectomy were chosen for this study; 21 cases of selective drainage (group
      A) and 12 cases of non-selective drainage (group B). The results are noted below.
      1) Both Am and Tr values of group A in the exudate from remnant pancreatic stump
      were statistically higher than those of group B (p < 0.01). Mean values of group
      A and group B on the first post-operative day were 25.6 x 10(4) versus 2.6 x
      10(4)IU/L (Am value) and 324.4 x 10(4) versus 12.2 x 10(4)ng/ml (Tr value),
      respectively. 2) The mean values rapidly decreased and bottomed on the sixth
      postoperative day. 3) Not only total drainage amount of Am (sigma Am: sum of Am
      value x exudate volume from each drain) but also sigma Tr in group B were
      markedly less than in group A (p < 0.01). It means that more than 40% of
      pancreatic juice remained in the abdomen without drainage in group B. In
      conclusion, effective and active drainage of remnant pancreatic stump for the
      initial three days at least is important to prevent complications and our
      selective drainage is one of the excellent methods.

PMID- 7510015
TI  - [Multiple abdominal organ transplantation in swine using FK-506].
AB  - Multiple abdominal organs including the liver, pancreas, stomach, and small and
      large intestine were allografted in pigs receiving intramuscular injections of FK
      506 (0.1, 0.15, 0.3, 0.4mg/kg/day). I observed rejection of the liver, and small
      and large intestine after 7 days post-transplantation in the untreated group.
      However, I did not observe rejection in all treated groups. The mean survival of
      the treated group (17.5, 8.5, 14, 10 days) was not significantly longer than that
      of the untreated group (10.8 days). Lymphocyte depletion and atrophy of the
      germinal center in the mediastinal lymph node were noted in the untreated group
      after 11 days post-transplantation, however, these were not noted in the treated
      groups. The histological improvement in animals receiving FK-506 was consistent
      with both suppression of rejection and the graft versus host reaction. I conclude
      that FK-506 is useful and powerful immunosuppressant for multiple abdominal organ
      transplantation in pigs.

PMID- 7510014
TI  - [Levels of soluble CD14 in patients with septic multiple organ failure (MOF):
      preliminary report].

PMID- 7510018
TI  - The Tn5 bleomycin resistance gene confers improved survival and growth advantage
      on Escherichia coli.
AB  - The bleomycin resistance gene (ble) of transposon Tn5 is known to decrease the
      death rate of Escherichia coli during stationary phase. Bleomycin is a DNA
      damaging agent and bleomycin resistance is produced by improved DNA repair which
      also requires the host genes aidC and polA coding, respectively, for an
      alkylation-inducible gene product and DNA polymerase I. In the absence of the
      drug, this DNA repair system is believed to cause the slower death rate of
      bleomycin-resistant bacteria. In this study, the effect of ble and aidC genes on
      the viability of bacteria and their growth rate in chemostat competitions was
      studied. The results indicate, that bleomycin-resistant bacteria display greater
      fitness under these conditions. Another beneficial effect of transposon Tn5 had
      been previously attributed to the insertion sequence IS 50 R. We were not able to
      reproduce this result with IS 50 R, however, the complete transposon was
      beneficial under similar conditions. Moreover, we showed the Tn5 fitness effect
      to be aidC-dependent. The ble gene was discovered after the fitness effect of IS
      50 R had been established; it has not previously been considered to mediate the
      beneficial effect of Tn5. This possibility is discussed based on the molecular
      mechanism of bleomycin resistance.

PMID- 7510017
TI  - Reduced but accurate translation from a mutant AUA initiation codon in the
      mitochondrial COX2 mRNA of Saccharomyces cerevisiae.
AB  - We have changed the translation initiation codon of the COX2 mRNA of
      Saccharomyces cerevisiae from AUG to AUA, generating a mutation termed cox2-10.
      This mutation reduced translation of the COX2 mRNA at least five-fold without
      affecting the steady-state level of the mRNA, and produced a leaky nonrespiratory
      growth phenotype. To address the question of whether residual translation of the
      cox2-10 mRNA was initiating at the altered initiation codon or at the next AUG
      codon downstream (at position 14), we took advantage of the fact that the mature
      coxII protein is generated from the electrophoretically distinguishable coxII
      precursor by removal of the amino-terminal 15 residues, and that this processing
      can be blocked by a mutation in the nuclear gene PET2858. We constructed a
      pet2858, cox2-10 double mutant strain using a pet2858 allele from our mutant
      collection. The double mutant accumulated low levels of a polypeptide which
      comigrated with the coxII precursor protein, not the mature species, providing
      strong evidence that residual initiation was occurring at the mutant AUA codon.
      Residual translation of the mutant mRNA required the COX2 mRNA-specific activator
      PET111. Furthermore, growth of cox2-10 mutant strains was sensitive to
      alterations in PET111 gene dosage: the respiratory-defective growth phenotype was
      partially suppressed in haploid strains containing PET111 on a high-copy-number
      vector, but became more severe in diploid strains containing only one functional
      copy of PET111.

PMID- 7510021
TI  - Mutagenic bioassay of certain pharmacological drugs: III. Metronidazole (MTZ).
AB  - The genotoxic activity of MTZ was evaluated in vitro with the anaphase-telophase
      test in a CHO cell line, chromosomal aberration and micronucleus test in
      lymphocyte cultures, and in vivo using the micronucleus test in mouse bone marrow
      cells. The In vivo test was performed using clinical trial doses (23, 70 and 160
      mg/kg). A significant increase in micronucleated cells (p < 0.02) was observed in
      the three assayed doses with a linear dose response (r = 0.91). In vitro studies
      showed a significant increase in the percentage of abnormal anaphases (p < 0.05),
      in chromosome aberrations (p < 0.01) and in the frequency of micronuclei (p <
      0.02) at all the concentrations assayed (0.1, 1 and 10 micrograms/ml). These
      findings demonstrate the clastogenic effect of this drug which should be taken
      into account considering its wide human consumption.

PMID- 7510023
TI  - Genotoxic activity of mebendazole in Aspergillus nidulans.
AB  - Mebendazole is an anthelmintic drug widely used in Cuba and in Mexico. Its
      interaction with tubulin interferes with the assemblage of the mitotic apparatus
      in the parasite cells, thus suggesting a possible genotoxic activity leading to
      chromosomal malsegregation. The heterozygous diploid strain D30 of Aspergillus
      nidulans was used to establish the ability of mebendazole to induce mitotic
      recombination and/or chromosomal non-disjunction, and the haploid strain FGSC
      #219 of A. nidulans was used to study the ability of mebendazole to induce point
      mutations in the methG suppressor system. Our results show that mebendazole can
      induce chromosomal non-disjunction but it fails to promote point mutations.

PMID- 7510020
TI  - The SOS function-inducing activity of the new nitrothiophenic derivatives in
      Escherichia coli.
AB  - Genotoxicity and cytotoxic effects of eight new nitrothiophenic compounds with
      trypanocidal activity were determined by means of the SOS Chromotest assay. Our
      results indicate that all nitro compounds with one aromatic ring in the R group
      were genotoxic without and with metabolic activation. The compounds with two
      aromatic rings in the R group, except for indazol-1-yl, were strongly cytotoxic
      but they were unable to induce SOS functions without metabolic activation.
      However, after metabolic activation no cytotoxic effect was observed for these
      compounds. The role of the nitroreductases to explain the different genotoxic
      responses of these nitrothiophenic derivatives is discussed.

PMID- 7510019
TI  - Control of replication of the Lactobacillus pentosus plasmid p353-2: evidence for
      a mechanism involving transcriptional attenuation of the gene coding for the
      replication protein.
AB  - The synthesis of plasmid DNA and of RNA encoded by the replication protein gene
      (rep) of plasmid p353-2 of Lactobacillus pentosus was studied for the wild-type
      plasmid and for a mutant plasmid with a deletion in the 5' untranslated region of
      the rep gene. Plasmid p353-2 codes for two countertranscript RNAs (CT-RNA) of
      approximately 75 and 250 nucleotides transcribed from the 5' untranslated region
      of the rep gene, in opposite directions. In a mutant plasmid with a deletion of
      the promoter and part of the CT-RNA-encoding sequence which shows a 5- to 10-fold
      increase in copy number compared to the wild-type plasmid, no CT-RNA could be
      detected. In the wild-type plasmid more than 90% of transcription initiated at a
      promoter upstream of the rep gene is prematurely terminated to form a 190
      nucleotide truncated RNA, whereas in the mutant plasmid nearly all transcripts
      reach a size (1100 nucleotides) corresponding to that of the rep gene. A model is
      presented for the role of CT-RNA in control of plasmid replication, similar to
      that previously presented for the staphylococcal plasmid pT181, involving a
      mechanism of transcriptional attenuation of rep RNA at a site just upstream of
      the rep gene.

PMID- 7510022
TI  - Lymphocyte proliferation kinetics and sister-chromatid exchanges in individuals
      treated with metronidazole.
AB  - Metronidazole, an effective agent for the treatment of protozoan infections, is
      frequently used in developing countries. However, the employment of this drug has
      been questioned in view of its mutagenicity in bacteria and carcinogenicity in
      mice. A genotoxic study was carried out in which cellular proliferation kinetics
      and the frequency of sister-chromatid exchanges were determined in human
      peripheral blood lymphocytes from 12 individuals treated with therapeutic doses
      of metronidazole. No effect was observed on mitotic index with the treatment,
      although a significant increase was found in three individuals after treatment.
      No increase of sister-chromatid exchanges was detected. The rate of lymphocyte
      proliferation kinetics showed an increase after the metronidazole treatment in
      all patients, indicating a possible immunostimulatory action.

PMID- 7510025
TI  - Assessment of interactions of the antimalarial drugs chloroquine and mefloquine
      with NaNO2 and HgCl2 in rodents.
AB  - Chloroquine and mefloquine are antimalarial drugs widely used in Brazil,
      especially in prospecting areas in the Amazonian region, where they may be
      associated with other compounds suspected to be genotoxic. Mefloquine was tested
      at doses of 150, 300, 600 and 1200 mg/kg body weight on Wistar rats and the
      animals were killed 6, 12 and 24 h later. No significant increase in chromatid
      gaps or breaks was induced by any of the treatments. The drugs were associated
      with NaNO2 and HgCl2, and a slight induction of chromatid aberration frequencies
      occurred with NaNO2, particularly when associated with chloroquine. The HgCl2 did
      not show clastogenic activity in bone marrow cells of Wistar rats or induce
      micronuclei in BALB/c mice. The association of chloroquine and mefloquine did not
      induce any clastogenic effect.

PMID- 7510024
TI  - The anticlastogenic effect of tocopherol in peritoneal macrophages of
      benznidazole-treated and ovariectomized mice.
AB  - Cytogenetic studies revealed a significant increase in the frequency of
      structural chromosome aberrations of peritoneal macrophages from hyperimmune
      Swiss mice after ovariectomy. The administration of the nitroarene benznidazole
      caused a large number of chromosomal deletions in peritoneal macrophages of sham
      ovariectomized animals. The clastogenic effect of benznidazole was much greater
      in peritoneal macrophages of ovariectomized mice. The anti-oxidant alpha
      tocopherol protected the peritoneal macrophages from developing ovariectomy- or
      benznidazole-induced chromosomal aberrations, thus suggesting free radical damage
      in these processes.

PMID- 7510026
TI  - Metabolic activation of four drugs in the eye mosaic assay measuring principally
      mitotic recombination in Drosophila melanogaster: differences in strain
      susceptibility and route of exposure.
AB  - One mycotoxin and three therapeutic drugs widely used in developing countries
      were examined for genotoxic activity by means of the w/w + somatic recombination
      assay. Streptozotocin (SZ), an antibiotic antineoplastic agent, gave a frequency
      of light spots almost one order of magnitude higher than those obtained with the
      carcinogen mycotoxin sterigmatocystin (STC), the antiprotozoal and antimicrobial
      metronidazole (MNZ), and the antifungal griseofulvin (GF). Thus the order of
      response was SZ > STC > MNZ > GF. Chronic treatment turned out to be the better
      route of exposure for these genotoxins when compared with surface treatment. The
      performance of the insecticide-resistant strain Hikone-R was better than that of
      the wild genotype LS (Leiden Standard). The positive test results obtained with
      all four chemicals showed that the P450 system of Drosophila is capable of
      metabolizing these genotoxins into electrophilic intermediates.

PMID- 7510027
TI  - Praziquantel (antischistosomal drug): is it clastogenic, co-clastogenic or
      anticlastogenic?
AB  - Schistosoma haematobium infection is the most common health problem in Egypt. It
      is strongly associated with the development of urinary bladder carcinoma. The
      actual cause for the development of cancer is still under investigations, it can
      be due to mechanical irritation from schistosomiasis ova, the infection itself or
      the drugs which are used to treat the patients. Praziquantel (PQ) is a commonly
      used drug to treat schistosomiasis patients. In mice, an in vivo cytogenetic
      study showed that PQ is not clastogenic in mice. The frequency of micronuclei in
      all the study groups were insignificantly different from the control group (p >
      0.05). However, it enhanced the clastogenicity of benzene at a very high dose.
      Results from combined exposure with benzene and PQ showed a significant PQ dose
      dependent increase in micronucleus frequency (p < 0.05). A metabolite study
      revealed that PQ enhanced the metabolism of benzene to form muconaldehyde which
      may be responsible for the enhancement effect. In schistosomiasis patients, two
      cytogenetic studies were carried out before and after treatment with PQ. In one
      of these studies, peripheral blood lymphocytes were examined from schistosomiasis
      patients to detect chromosomal aberrations (CAs) and micronuclei (MN) before and
      after treatment with PQ. There was no significant increase in CAs in patients
      compared with the controls (p > 0.05). The frequency of MN was significantly
      higher in the infected persons (0.59 +/- 0.44) than the control individuals (0.23
      +/- 0.23) (p < 0.05). After treatment, there was no significant change in both
      parameters. The other study was conducted to determine whether infection with
      this parasite resulted in an increase of chromosomal breakage, micronuclei, in
      exfoliated urothelial cells. Micronucleus frequencies were significantly higher
      in the infected group (mean frequency, 0.84 +/- 0.69%) than among controls (mean
      frequency, 0.12 +/- 0.21%, p < 0.001). Micronucleus frequencies were higher in
      infected individuals who smoked compared with those who were non-smokers,
      although this effect was not significant (p > 0.05). The mean micronucleus
      frequencies were reduced significantly in the group of patients who were followed
      up (before treatment, 0.80 +/- 0.70%, after treatment, 0.19 +/- 0.23%, p <
      0.001), thus supporting a direct involvement of the infection in increased
      chromosomal breakage in the urothelium and provide proof of the role of PQ in
      decreasing the risk of cancer development. At this stage, we still need to study
      the cytogenetic effect of human exposure to environmental agents such as
      pesticides, smoking, etc., together with treatment with PQ.

PMID- 7510029
TI  - Mutation at the HPRT locus in patients with neurocysticercosis treated with
      praziquantel.
AB  - Praziquantel (PZQ) is the drug of choice in the treatment of neurocysticercosis
      (NC), a parasitic disease caused by Taenia solium larvae. Variant frequencies at
      the hprt locus were analyzed in a group of NC patients before and after treatment
      with PZQ as well as in two control groups: healthy donors and non-parasitic
      neurological patients. Data show that PZQ does not induce hprt mutations, but
      that cysticerci by themselves or together with palliative treatment administered
      to NC patients could induce mutations in some patients.

PMID- 7510030
TI  - Chagas' disease: carcinogenic activity of the antitrypanosomal nitroarenes in
      mice.
AB  - The carcinogenic activity of antitrypanosomal 2-nitroimidazole, 5-nitroimidazole
      and 5-nitrofuran derivatives was assessed in female Swiss mice of the same age
      group. A statistically significantly higher incidence of growths was seen in mice
      into which 2-nitro had been injected than in mice receiving 5-nitro derivatives
      intraperitoneally. A histologic type of lymphoblastic lymphoma that invades lymph
      nodes, spleen, liver, lungs and lymphatic tissue elsewhere was frequently found
      in nitroarene-treated mice. Further, it is shown that the potency of the drug,
      rather than the duration of its administration, was usually associated with the
      growth of lymphomas. The 2-nitro derivative which induced the highest incidence
      of lymphomas significantly decreased the survival of treated mice; this probably
      occurred because it undergoes enzymatic reduction of the nitro group more
      efficiently than the 5-nitro compounds used. The differences of incidence of
      lymphomas in mice receiving any of these nitroarenes and in control mice that
      received daily injections of 0.15 M saline were statistically significant (alpha
      = 0.05). The indiscriminate use of these nitroarenes to treat Trypanosoma cruzi
      infections in man could therefore induce a significant number of lymphomas.

PMID- 7510031
TI  - Possible integration of Trypanosoma cruzi kDNA minicircles into the host cell
      genome by infection.
AB  - Infection with Trypanosoma cruzi is known to induce the division of peritoneal
      macrophages in BALB/c mice. We have demonstrated, by cytogenetic analysis, that
      accessory DNA elements are associated with the metaphase macrophage chromosomes
      of such infected macrophages. The identification of these accessory DNA elements
      with T. cruzi DNA is strongly supported by the association of 3H-label with some
      chromatids in macrophages previously infected with T. cruzi which had been
      labelled with 3H-methyl-thymidine. The karyotyping consistently showed
      preferential associations of T. cruzi DNA with chromosomes 3, 6 and 11. A
      conclusive demonstration of the parasite origin of the integrated DNA came from
      fluorescein in situ hybridization studies using specific parasite DNAs as probes.
      In order to determine the identity of the inserted DNA and to investigate the
      nature of the integration mechanism, Southern blot analyses were performed on DNA
      extracted from both uninfected and infected (but parasite-free) macrophages.
      Hybridizations of BamHI, EcoRI and TaqI digests of DNA from T. cruzi-infected
      host cells all revealed the presence of a 1.7-kb DNA fragment when probed with
      kDNA. The covalent association of kDNA with that of the host was confirmed by the
      fact that AluI and Hinf-I digests of DNA from infected host cells produced a
      number of bands, in a size range of 0.8-3.6 kb, which hybridized with kDNA
      minicircles. None of these bands was found in DNA purified from cell-free
      preparations of the parasite and thus it must be concluded that they represent
      insertion fragments between parasite and host cell DNA. These results strongly
      suggest that kDNA minicircles from T. cruzi have been integrated into the genome
      of the host cell following infection.

PMID- 7510028
TI  - Evaluation of the carcinogenic and genotoxic potential of praziquantel in the
      Syrian hamster embryo cell transformation assay.
AB  - Praziquantel, a drug used for the treatment of neurocysticercosis, was tested for
      its ability to induce morphological transformation of Syrian hamster embryo
      fibroblasts. Results indicate that praziquantel transforms these cells without
      affecting their viability. Further experiments were carried out to investigate
      its possible mechanism of action in the same cell system. Micronucleus formation
      was observed in cultures treated with concentrations which induced morphological
      transformation, about 40% of these micronuclei were positive to a kinetochore
      antibody. No induction of DNA repair synthesis was observed even at cytotoxic
      concentrations. These results suggest that praziquantel has an aneugenic effect
      which could be responsible for its ability to transform morphologically these
      cells. Risk-benefit analysis should be carried out whenever this drug is
      utilized.

PMID- 7510032
TI  - Genotoxic effects of Mycobacterium leprae infection in humans.

PMID- 7510033
TI  - Immune response impairment, genotoxicity and morphological transformation induced
      by Taenia solium metacestode.
AB  - In chronic helminthic infections such as cysticercosis, where the parasites live
      for years, profound modulation of the host immune response has been reported. To
      evaluate the genotoxicity of a drug used to treat cysticercosis, we observed the
      occurrence of genetic damage in cultured lymphocytes from cysticercotic swine and
      patients who had not been exposed to the drug. The human lymphocytes also showed
      a slower proliferation. These data suggested that the disease itself was
      promoting genetic damage in host lymphocytes which, in part, could explain the
      retardation of the lymphocyte proliferation observed in cysticercotic patients.
      Pigs infected with Taenia solium cysticerci showed an increased lymphocyte
      proliferation for 6-8 weeks post infection, followed by an impaired proliferation
      after this period. Significant induction of sister-chromatid exchanges was also
      observed in lymphocytes from infected pigs after the 6th week post infection.
      Additionally, it was found that a factor secreted by the cysticerci
      morphologically transformed primary fibroblasts in culture. The results strongly
      suggest that the parasite produces genetic instability in the host cells, which
      could result in immunosuppression and malignant transformation of target cells.

PMID- 7510035
TI  - Liver fluke infection and cholangiocarcinoma: model of endogenous nitric oxide
      and extragastric nitrosation in human carcinogenesis.
AB  - Cancers arising during bacterial, viral and parasitic infection provide useful
      models to investigate the link between inflammation and carcinogenesis. Because
      the inflammatory agent is known, relationships between immune responses, the
      production of DNA-damaging agents, such as nitric oxide, oxygen radicles and N
      nitroso compounds, and cancer risk can be explored. This paper first describes
      the close relationship between infection with the liver fluke, Opisthorchis
      viverrini, and cholangiocarcinoma in humans. Data are then presented which
      demonstrate an elevation in levels of salivary nitrite and urinary and plasma
      nitrate among men with moderate and heavy liver fluke infections compared to
      uninfected controls which was absent 4 months after the parasites were cleared
      with praziquantel. Because of the strict control over subject selection and
      dietary intake plus the absence of the increase following treatment, we conclude
      that the higher levels of nitrate and nitrite reflect endogenous generation of
      nitric oxide resulting from liver fluke infection. Excess nitric oxide generation
      in the inflamed tissue is likely to lead directly to the formation of N-nitroso
      compounds mediated by activated macrophages. Further work will attempt to
      demonstrate a link between this increase and both parasite-specific immune
      responses and the risk of cancer.

PMID- 7510034
TI  - Invasion and metastasis mechanisms in Entamoeba histolytica and cancer cells.
      Some common cellular and molecular features.

PMID- 7510036
TI  - Chronic infections and inflammatory processes as cancer risk factors: possible
      role of nitric oxide in carcinogenesis.
AB  - Infection by bacteria, parasites or viruses and tissue inflammation such as
      gastritis, hepatitis and colitis are recognized risk factors for human cancers at
      various sites. Nitric oxide (NO) and other oxygen radicals produced in infected
      and inflamed tissues could contribute to the process of carcinogenesis by
      different mechanisms, which are discussed on the basis of authors' studies on
      liver fluke infection and cholangiocarcinoma development. A similar mechanism
      could apply to other suspected and known cancer-causing agents including
      Helicobacter pylori infection (stomach cancer) or asbestos exposure (lung
      mesothelioma). Studies on the type of tissue and DNA damage produced by NO and by
      other reactive oxygen species are shedding new light on the molecular mechanisms
      by which chronic inflammatory processes may initiate or enhance carcinogenesis in
      humans.

PMID- 7510037
TI  - Retention of a mutagen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), in the
      liver of mice infected with Schistosoma japonicum.
AB  - Regarding the mechanism underlying the suspected enhancement of hepatic cancers
      among Schistosoma japonicum-infected humans, we hypothesized that mutagen
      exposures in the livers of patients may be enhanced due to the parasitic
      infection. To explore this possibility, we have done a model experiment using
      mice and a carcinogenic mutagen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P
      2). Mice infected with Schistosoma japonicum were intravenously administered Trp
      P-2, and the mutagenic activities of the mouse serum and of the liver tissue
      extracts, which were observable during the 6-h period after the administration,
      were investigated. The level of serum indirect mutagenicity, which probably
      reflected the amount of unmetabolized Trp-P-2, was higher in the infected animals
      than in uninfected control animals. Direct mutagenicity in the serum, on the
      other hand, was higher in the control animals than in the infected mice.
      Furthermore, the liver tissue extracts from infected mice showed higher indirect
      mutagenicity than those from the controls. These data suggest that the infection
      results in a decreased metabolism and an increased retention of Trp-P-2 in the
      liver. Consistent with this phenomenon, pigments in the liver formed by the
      schistosome infection were found to be an efficient adsorbent for Trp-P-2. Thus,
      the possibility exists that these pigments, which contain hematin as a major
      constituent, may function as a reservoir for the mutagen, thereby prolonging the
      exposure period of the liver to the mutagen.

PMID- 7510038
TI  - Parasite infection and cancer: with special emphasis on Schistosoma japonicum
      infections (Trematoda). A review.
AB  - This article contains a review of current knowledge on the association of
      parasite infections and cancer formation, especially that of Schistosoma
      japonicum (Trematoda) in man and experimental animals. The association of S.
      haematobium infection and bladder cancer is well known and documented. However,
      S. japonicum infection has also been reported to be associated with cancer, in
      this case hepatocellular carcinoma and/or colorectal cancer. Pathological records
      and analyses have shown a correlation between this infection and cancer, and
      pathohistological descriptions have been numerous, together with clinical case
      reports. Epidemiological analyses have been conducted in China and Japan and
      support a role of S. japonicum infection as one of the risk factors in cancer
      formation, along with others, such as hepatitis virus infection and alcoholic
      intake. Experimental results have also shown that cancer appears early and in
      larger numbers in experimentally infected animals given a known carcinogen. In
      spite of these positive end-point associations, the mechanism of schistosome
      mediated enhancement of carcinogenesis is obscure. A suggestive observation is
      that in S. japonicum-infected mice carcinogen-metabolizing hepatic activity
      including P-450 was decreased so that an administered carcinogen persisted for a
      longer period than in uninfected mice. Further studies, both epidemiological and
      experimental, are needed to firmly establish the relationship between schistosome
      infection and cancer.

PMID- 7510039
TI  - Involvement of inflammatory reactions and elevated cell proliferation in the
      development of bladder cancer in schistosomiasis patients.
AB  - Schistosoma haematobium infection is strongly associated with urinary bladder
      cancer. Although numerous explanations have been proposed for this association,
      the nature of this relationship remains unresolved. This paper explores the
      hypothesis that inflammation and elevated cell proliferation play a major role in
      the development of bladder cancer in infected patients, possibly by increasing
      the level of genetic instability in the urothelium. The paper details in vivo and
      in vitro studies being done in our laboratories to test this hypothesis. These
      studies include population studies in which chromosomal breakage in the bladder
      of infected individuals is assayed using the micronucleus (MN) test on exfoliated
      urothelial cells. The approach also includes parallel studies in Vancouver with
      patients with long-term catheter drainage, a population with many similarities to
      schistosomiasis patients. In the in vitro studies we are co-incubating bladder
      cells with activated neutrophils or experimental conditions simulating
      inflammation. These studies show that inflammatory cells when activated can
      induce micronuclei in bladder cells and that this response is associated with
      loci on chromosome 11, a chromosome commonly altered during bladder
      carcinogenesis. A final approach being used is to assay chromosomal change (MN
      frequencies and numerical chromosome alterations) and level of proliferation
      (expression of proliferating cell nuclear antigen) in archival biopsies from
      schistosomiasis patients. Preliminary results show that a dysregulation of cell
      proliferation is occurring during cystitis in these patients. The extent to which
      this alteration affects the level of chromosomal breakage is yet to be
      determined.

PMID- 7510040
TI  - The tumor suppressive properties of adeno-associated viruses.

PMID- 7510041
TI  - Implications for the involvement of the immune system in parasite-associated
      cancers.
AB  - Biological factors can be carcinogenic risk factors in humans and in animals.
      Numerous theories have been developed to explain the causal link between
      biologically-associated disease and the ensuing neoplasia. In this paper we
      discuss the merits of one of these theories, the possible association between the
      mammalian inflammatory response and cancer.

PMID- 7510042
TI  - Brief report: prenatal diagnosis of X-linked hyper-IgM syndrome.

PMID- 7510043
TI  - Structure of the Aeromonas toxin proaerolysin in its water-soluble and membrane
      channel states.
AB  - Aerolysin is chiefly responsible for the pathogenicity of Aeromonas hydrophila, a
      bacterium associated with diarrhoeal diseases and deep wound infections. Like
      many other microbial toxins, the protein changes in a multistep process from a
      completely water-soluble form to produce a transmembrane channel that destroys
      sensitive cells by breaking their permeability barriers. Here we describe the
      structure of proaerolysin determined by X-ray crystallography at 2.8 A
      resolution. The protoxin (M(r) 52,000) adopts a novel protein fold. Images of an
      aerolysin oligomer derived from electron microscopy have assisted in constructing
      a model of the membrane channel and have led to the proposal of a scheme to
      account for insertion of the protein into lipid bilayers to form ion channels.

PMID- 7510044
TI  - The value of PSA screening.

PMID- 7510045
TI  - [Alternative treatments in cancer; extent and background of utilization].
AB  - OBJECTIVE: To determine the prevalence of use of alternative cancer therapies, as
      well as the characteristics of the patients who use these therapies, and their
      experiences with them. DESIGN: Descriptive study. SETTING: Outpatient departments
      of several hospitals in North-Holland. METHOD: In total, 1091 patients were asked
      to participate in the study; 949 patients agreed (87%): 535 women (56%) and 414
      men, with an average age of 62 years. The sample was stratified by diagnosis: 233
      breast, 183 lung, 278 stomach/colon cancer and 255 patients with various other
      cancer diagnoses. A structured face-to-face interview and several written
      questionnaires were used. RESULTS: 2XOf the 949 patients, 9.4% were currently
      using an alternative therapy in addition to conventional treatment, and 5.8% had
      used an alternative treatment in the past but had subsequently stopped. Patients
      using alternative therapies were relatively younger and more highly educated than
      patients who chose not to use these therapies. Use of alternative therapies was
      more frequent among patients undergoing palliative treatment and patients who
      were actively dealing with the problems surrounding their disease. Only a
      minority of the patients believed they could be cured by the alternative therapy;
      the majority hoped it would help to slow the progression of their disease or
      strengthen their resistance. CONCLUSION: The motivation for seeking alternative
      treatment more often appears to be fear and uncertainty rather than belief in the
      efficacy of the treatment. For many patients the use of alternative therapies
      represents a means of dealing with the anxiety and stress surrounding their
      disease.

PMID- 7510046
TI  - [Health problems following very premature birth; 9-year follow-up].

PMID- 7510047
TI  - CSF drains directly from the subarachnoid space into nasal lymphatics in the rat.
      Anatomy, histology and immunological significance.
AB  - Cerebrospinal fluid (CSF) drainage pathways from the rat brain were investigated
      by the injection of 50 microliters Indian ink into the cisterna magna. The
      distribution of the ink, as it escaped from the cranial CSF space, was documented
      in 2 mm thick slices of brain and skull cleared in cedar wood oil and in
      decalcified paraffin sections. Following injection of the ink, deep cervical
      lymph nodes were selectively blackened within 30 min and lumbar para-aortic nodes
      within 6 h. Within the cranial cavity, carbon particles accumulated in the basal
      cisterns but were also distributed in the paravascular spaces around the middle
      cerebral arteries and the nasal-olfactory artery. Carbon particles in the
      subarachnoid space beneath the olfactory bulbs drained directly into discrete
      channels which passed through the cribriform plate and into lymphatics in the
      nasal submucosa. Although ink was distributed along the subarachnoid space of the
      optic nerves and entered the cochlea, the nasal route was the only direct
      connection between cranial CSF and lymphatics. Arachnoid villi associated with
      superior and inferior sagittal sinuses were identified and a minor amount of
      drainage of ink into dural lymphatics was also observed. This study demonstrates
      the direct drainage of cerebrospinal fluid through the cribriform plate in
      anatomically defined channels which connect with the nasal lymphatics.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7510048
TI  - Anti-NKH-1 antibody specifically stains unmyelinated fibres and non-myelinating
      Schwann cell columns in humans.
AB  - Anti-NKH-1 antibody recognizes an isoform of the neural cell adhesion molecule (N
      CAM) that is involved in cell-cell interactions during embryonic stages and has
      been detected in skin autonomic nerves. The specificity of anti-NKH-1 antibody
      for human unmyelinated fibres (UF) and the distribution of the antigens
      recognized by this antibody at the ultrastructural level, were evaluated by
      immunohistochemistry and immunoelectron microscopy on nerve biopsy samples from
      patients with normal nerve biopsies and a variety of peripheral neuropathies. The
      anti-NKH-1 antibody strongly stained all unmyelinated fibres while no myelinated
      fibre was stained. Autonomic nerve fibres were visualized at the periphery of
      blood vessels. Immunoelectron microscopy showed that the antigen recognized by
      the antibody was located at Schwann cell-axon interfaces and in portions of
      joined Schwannian surfaces, i.e. along mesaxons of non-myelinating Schwann cells.
      Expression of NKH-1 was basically similar in normal and diseased nerves as
      expression of NKH-1 was similar at the level of apposed plate-like Schwann cell
      processes than along normal mesaxons. The extent of labelling of diseased nerves
      by the anti-NKH-1 antibody likely depended on the number of residual Schwann cell
      columns observed by light microscopy.

PMID- 7510049
TI  - A rapid and non-radioactive PCR based assay for the detection of allelic loss in
      human gliomas.
AB  - Studies of the loss of allelic heterozygosity (LOH) in tumour tissues have
      evolved as an important tool for the identification of chromosomal regions which
      are likely to harbour tumour suppressor genes. The classical procedure to
      determine LOH has been restriction fragment length polymorphism (RFLP) analysis
      and Southern blotting, a time consuming method requiring radioisotopes and
      several micrograms of DNA. Recently, the use of highly polymorphic
      microsatellites of the CA-dinucleotide repeat class and polymerase chain reaction
      (PCR) has considerably advanced and facilitated the detection of LOH in tumour
      tissues. We here describe a strategy to identify LOH based on PCR amplification
      of CA-dinucleotide repeats, denaturing polyacrylamide gel electrophoresis (PAGE)
      and nucleic acid detection with a sensitive silver staining protocol. In a
      comparative study of 20 astrocytomas, this rapid technique was able to identify
      all cases of LOH on chromosome 17 p that had previously been found in these
      tumours by RFLP analysis and Southern blotting. This non-radioactive PCR based
      assay has a great potential for LOH studies in human tumours.

PMID- 7510050
TI  - Histological characteristics and expression of acidic and basic fibroblast growth
      factor genes in intracerebral xenogeneic transplants of human glioma cells.
AB  - Eleven athymic nude rats had stereotactic intracerebral inoculation of cells from
      one of three established human glioma cell lines (A172, A1207, and A1235). The
      implants grew progressively in 9 of 11 instances, which led to spontaneous death
      of the host in 14 to 37 days. For comparison, two Sprague-Dawley normal albino
      rats were implanted with the rat C6 glioma cell line. One rat died at 14 days,
      and the other was killed at Day 16. The human glioma cells developed into
      partially (A172, A1235) or totally (A1207) circumscribed tumor masses. Invasion,
      when present, was manifested as infiltrating prongs of cells rather than as
      individual cell infiltration. The growth of the human glioma cells was
      accompanied by a small zone of surrounding edema and marked central necrosis.
      These features were not encountered in the C6 implants. Inflammatory changes were
      minimal to nonexistent in all cases. All tumor lines produced internal cerebral
      herniation and neuraxis spread with implants seeded throughout the ventricular
      system, often associated with ventricular dilation. In situ hybridization, by the
      use of isotopic and nonisotopic detection methods, was used to study the cellular
      expression of the acidic fibroblast growth factor and basic fibroblast growth
      factor genes in A172 glioma xenografts. The expression of these genes was not
      seen in normal rat brain, but the genes were selectively overexpressed by the
      glioma cell implants, with especially high signal in the tumor
      periphery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510051
TI  - Nitric oxide synthase-immunoreactive neurons in human and porcine respiratory
      tract.
AB  - The presence of nitric oxide synthase (NO-synthase), the enzyme responsible for
      the production of nitric oxide (NO) from L-arginine, is shown
      immunocytochemically in the intrinsic neurons of the human and porcine
      respiratory tract. NO-synthase immunoreactivity is demonstrated in a
      subpopulation of neurons of the microganglia present in the wall of the extra-
      and intrapulmonary bronchi as well as in the hilar region of the lung in relation
      to blood vessels. The immunostaining was also found in some nerve fibers of the
      respiratory nervous system. Human and porcine lung gave similar results. The
      possible involvement of NO in the nonadrenergic noncholinergic (NANC) nervous
      regulation of the lung is discussed.

PMID- 7510052
TI  - 'Perineuronal nets' around cortical interneurons expressing parvalbumin are rich
      in tenascin.
AB  - 'Perineuronal nets' are ill-known structures enwrapping the cell bodies and
      proximal dendrites of certain neurons in the brain. It is as yet unclear if they
      represent a cytological entity or extracellular material. Using
      immunohistochemical methods we have detected the presence of the extracellular
      matrix-protein, tenascin, in the 'perineuronal nets' surrounding certain cortical
      interneurons. We have also shown that tenascin antibodies label the circumference
      of parvalbumin-immunoreactive neurons preferentially. We conclude that this
      classical matrix protein is a major component of 'perineuronal nets'. Therefore,
      'perineuronal nets' may represent sites of privileged adhesion between nerve and
      glial cells.

PMID- 7510053
TI  - Carbachol can potentiate N-methyl-D-aspartate responses in the rat hippocampus by
      a staurosporine and thapsigargin-insensitive mechanism.
AB  - Experiments were performed to investigate the mechanism underlying the
      potentiation of N-methyl-D-aspartate (NMDA) responses by carbachol (CCh) in the
      CA1 region of rat hippocampal slices. CCh (300 nM) potentiated responses to NMDA,
      but not to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), in a
      readily reversible manner. Potentiation occurred in slices treated with 200 nM
      tetrodotoxin and perfused with Mg(2+)-free medium. It also occurred in slices
      treated with either staurosporine (1 microM), which is a potent inhibitor of a
      variety of protein kinases including protein kinase C (PKC), or thapsigargin (10
      microM), which depletes intracellular Ca2+ stores by preventing their refilling.
      However, CCh-induced potentiation was abolished in slices perfused with Ca(2+)
      free medium. These data suggest that low concentrations of CCh can acutely
      potentiate NMDA responses in the hippocampus by a Ca(2+)-sensitive process that
      is probably independent of both the activation of PKC and the release of Ca2+
      from intracellular stores. This mechanism is similar to that underlying the
      potentiation of NMDA responses by the metabotropic glutamate receptor (mGluR)
      agonist, aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD).

PMID- 7510054
TI  - Synthesis and release of the beta-amyloid precursor protein by bovine chromaffin
      cells.
AB  - Production of the beta-amyloid precursor protein (beta APP) by bovine adrenal
      chromaffin cells was investigated by polymerase chain reaction (PCR) and by
      immunoblot. Chromaffin cells were found to synthesize forms of beta APP similar
      to those found in the rat PC12 pheochromocytoma cell line and to secrete these
      constitutively into their culture medium. Release of beta APP could be enhanced
      by stimulation with phorbol ester but not by cholinergic stimulation of
      secretion. The fact that normal chromaffin cells produce beta APP suggests that
      beta APP has some (as yet undermined) function in the adrenal medulla in vivo.

PMID- 7510055
TI  - Regionally selective stimulation of mitogen activated protein (MAP) kinase
      tyrosine phosphorylation after generalized seizures in the rat brain.
AB  - Immunoblot analysis using a phosphotyrosine-specific antibody was performed to
      investigate tyrosine phosphorylation of the mitogen activated protein (MAP)
      kinase in the rat brain. Epileptic seizures induced by systemic injection of
      bicuculline caused a rapid and transient stimulation of MAP kinase tyrosine
      phosphorylation in hippocampus and somatosensory cortex. This increase in
      tyrosine phosphorylation was markedly attenuated by the N-methyl-D-aspartate
      (NMDA) receptor antagonist MK-801. In contrast, in the cerebellum, tyrosine
      phosphorylation of MAP kinase remained undetectable after bicuculline-induced
      seizures. These results demonstrate that generalized seizures stimulate tyrosine
      phosphorylation of MAP kinase in a regionally selective manner.

PMID- 7510056
TI  - Expression of the gene coding for the NR1 subunit of the NMDA receptor during rat
      brain development.
AB  - Expression of the gene coding for the NR1 subunit of the N-methyl-D-aspartate
      (NMDA)-type of glutamate receptor was investigated in the developing rat brain.
      Peak NR1 gene expression in the whole brain occurred at approximately postnatal
      day (P) 10 with a second increase in the adult. To determine the ontogenic
      expression in the various brain regions, the expression of NR1 at P2, P10 and P60
      was compared. The regional studies indicated increased expression at P60 in the
      cerebellum. In the midbrain and diencephalon, levels of expression at P10 and P60
      were higher than at P2, while in the hippocampus, expression at P10 was
      significantly higher than at either P2 or P60. Expression in the other brain
      regions was constant over the period studied. These data indicate a region
      specific expression of NR1 in the central nervous system during ontogeny.

PMID- 7510057
TI  - Augmenting effects of cyclic AMP on the heat response of canine testicular
      polymodal receptors.
AB  - It has long been thought that the augmenting effects of E series prostaglandins
      (PG) are mediated by cyclic AMP (cAMP). In clarifying the validity of this
      hypothesis, we studied the effects of increases in intracellular cAMP on the heat
      response of testicular polymodal receptors. Recordings were obtained from testis
      spermatic nerve preparations excised from dogs anesthetized with pentobarbital
      (30 mg/kg, i.v.). Induction of increases in intracellular cAMP by either
      forskolin, an adenylyl cyclase activator, or a mixture of dibutyryl cAMP (10(-4)
      M) and 3-isobutyl-1-methyl xanthine (10(-4) M) significantly and reversibly
      augmented the heat response. These results support the notion that cAMP is
      involved in the augmenting effect of PG E2 on the heat response of nociceptors.

PMID- 7510058
TI  - Inhibitory effect of nitric oxide (NO) synthase inhibitors on naloxone
      precipitated withdrawal syndrome in morphine-dependent mice.
AB  - The effect of intraperitoneally administered nitric oxide (NO) synthase
      inhibitors has been examined on the naloxone-precipitated withdrawal syndrome in
      morphine-dependent mice. L-NAME (30-200 mg/kg) and L-NOARG (7.5-50 mg/kg) induced
      a significant decrease of naloxone-precipitated withdrawal jumping and diarrhoea.
      However, L-NMMA (3.5-100 mg/kg), considered as a less potent NO synthase
      inhibitor, did not significantly affect the withdrawal signs in mice. Although a
      specificity of NO synthase inhibitors is not fully established, these results
      indicate that inhibition of NO synthesis in the central nervous system and
      periphery may significantly affect the morphine withdrawal phenomena.
      Accordingly, this study suggests an involvement of NO in morphine withdrawal
      syndrome.

PMID- 7510059
TI  - Behavioral and immunohistochemical changes in an experimental arthritis model in
      rats.
AB  - An experimental arthritis induced by injection of kaolin and carrageenan into the
      knee joint resulted in a temporal relationship between glutamate dorsal horn
      content and paw withdrawal latency (PWL) which was positively correlated.
      Limping, guarding, increased response to heat stimuli (hyperalgesia) and altered
      staining patterns for glutamate (GLU), substance P (SP), and calcitonin gene
      related peptide (CGRP) were monitored in the awake behaving arthritic rat over a
      1 week time course. A decrease in PWL occurred on the side ipsilateral to the
      inflamed knee as early as 4 h after the induction of arthritis indicating the
      animals are hyperalgesic. The PWL remained decreased through the first 24 h.
      Computer-assisted quantification of the density of immunohistochemical staining
      indicated the content of GLU, SP and CGRP was altered differentially throughout
      the time course of the arthritis. The changes observed for all three substances
      occurred across the entire superficial dorsal horn. There was an initial
      depletion of SP followed by an increase in both SP and CGRP content which was
      maintained through 1 week. The GLU content was increased during the hyperalgesic
      period. The GLU changes followed the same time course and were positively
      correlated with the changes in PWL. In a small group of animals injected with
      kaolin and carrageenan, hyperalgesia did not develop. In this group of animals,
      no change in dorsal horn GLU or SP content occurred. Rather, there was an
      increase in CGRP content in the middle portion of the superficial dorsal horn
      which is the termination site of knee joint afferents. These data indicate that
      the development of heat hyperalgesia is dependent on GLU and possibly SP. Since
      inflammation of the knee joint does not involve the foot pad, the heat
      hyperalgesia observed during the first 24 h following induction of arthritis
      represents a central neuronal sensitization.

PMID- 7510060
TI  - Comments on Meller, S.T. and Gebhart, G.F., Pain, 52 (1993) 127-136.

PMID- 7510061
TI  - Toluene embryopathy: delineation of the phenotype and comparison with fetal
      alcohol syndrome.
AB  - OBJECTIVE: To determine if maternal toluene abuse produces any structural or
      developmental disabilities in the developing fetus, a cohort of toluene-exposed
      infants was ascertained and examined. METHODOLOGY: Eighteen infants with a
      history of in utero toluene exposure were examined at birth. Nine of these
      infants were reexamined 3 to 36 months after their initial evaluations. The
      clinical findings in these patients were compared with those of similarly exposed
      children from the literature and with patients who had the fetal alcohol
      syndrome. RESULTS: Thirty-nine percent of all toluene-exposed infants described
      in this and other studies were born prematurely, and 9% died during the perinatal
      period. Fifty-four percent were small for gestational age, and 52% exhibited
      continued postnatal growth deficiency. A 33% incidence of prenatal microcephaly,
      a 67% incidence of postnatal microcephaly, and an 80% incidence of developmental
      delay were observed. Eighty-three percent of the patients had craniofacial
      features similar to the fetal alcohol syndrome, and 89% of these children had
      other minor anomalies. CONCLUSIONS: Data from the patients herein described and
      the available scientific literature suggest that the mechanism of alcohol
      craniofacial teratogenesis may be nonspecific, with a variety of teratogens,
      including toluene, giving rise to phenotypic facial abnormalities similar to
      those of the fetal alcohol syndrome. We propose a common mechanism of
      craniofacial teratogenesis for toluene and alcohol, namely a deficiency of
      craniofacial neuroepithelium and mesodermal components due to increased embryonic
      cell death.

PMID- 7510062
TI  - Toluene embryopathy: clinical delineation and developmental follow-up.
AB  - OBJECTIVE: To expand the phenotype of toluene embryopathy. METHOD: Review of case
      records of 35 deliveries with antenatal exposure to toluene. Six children were
      examined and their features are compared with previously reported cases. RESULTS:
      There were three perinatal deaths. Of the survivors, review of available data
      revealed a high incidence of prematurity (42%), low birth weight (52%), and
      microcephaly (32%). Birth weight, length, and head circumference and gestational
      length were significantly less than a control group closely matched for gender,
      race, and socioeconomic status. Follow-up pediatric evaluation revealed growth
      retardation (46% < 5th percentile for weight, 38% < 5th percentile for height),
      microcephaly (46%), and developmental delays (38%). Maternal toluene abuse of 4
      or more years was positively correlated with weight < 5th percentile and
      microcephaly in childhood. The six children examined demonstrated many previously
      described features of toluene embryopathy including microcephaly, narrow
      bifrontal diameter, short palpebral fissures, hypoplastic midface, wide nasal
      bridge, abnormal palmar creases, and blunt fingertips. Only one of the six
      children examined had antepartum exposure to alcohol as well as toluene.
      CONCLUSION: In utero exposure to toluene seems to be associated with
      teratogenicity in the developing fetus. A preliminary picture of toluene
      embryopathy is now emerging.

PMID- 7510063
TI  - Prevention of intellectual impairment in children of women who smoke cigarettes
      during pregnancy.
AB  - OBJECTIVE: To analyze the influence of a comprehensive program of nurse home
      visitation on the intellectual functioning of children born to women who smoked
      cigarettes during pregnancy. DESIGN: Randomized clinical trial. Treatment 1:
      sensory and developmental screening at ages 1 and 2 years; treatment 2: screening
      plus free transportation for prenatal and well-child care; treatment 3:
      screening, transportation, plus prenatal home visitation; treatment 4: screening,
      transportation, prenatal home visitation, plus postnatal home visitation through
      the children's second birthdays. SETTING: Semi-rural community in Upstate New
      York. PARTICIPANTS: 400 families in which the mothers registered before the 30th
      week of pregnancy and had no previous live births. Eighty-five percent of the
      mothers were either teenagers, unmarried, or poor. Analysis was limited to
      whites, who constituted 89% of sample. INTERVENTION: Nurse home visitation during
      pregnancy (treatments 3 and 4) or during pregnancy and the first 2 years of the
      child's life (treatment 4). During pregnancy, the nurses helped women improve
      their health-related behaviors, informal social support, and linkage with needed
      community services. MAIN FINDINGS: Children born to women who smoked 10 or more
      cigarettes per day at registration during pregnancy and who were assigned to
      treatments 3 and 4 had IQs (averaging across the 3rd and 4th years of life) that
      were 4.86 (95% CI: 0.47, 9.26) points higher after adjustment for covariates than
      did children born to women who smoked 10+ cigarettes per day and who were
      assigned to treatments 1 and 2. The positive influence of the home-visiting
      program on reducing the harmful effect of smoking appears to be due to prenatal
      visitation. CONCLUSION: Comprehensive prenatal home-visitation services can
      offset the impairment in intellectual functioning associated with substantial
      maternal smoking during pregnancy.

PMID- 7510064
TI  - Neuron-specific enolase and myelin basic protein: relationship of cerebrospinal
      fluid concentrations to the neurologic condition of asphyxiated full-term
      infants.
AB  - OBJECTIVE: We questioned whether neuron-specific enolase (NSE) and myelin basic
      protein (MBP) concentrations in cerebrospinal fluid (CSF) in the first 72 hours
      of life are correlated with the neurologic condition of asphyxiated full-term
      infants in the neonatal period and at 1 year of age. PATIENTS AND METHODS: Sixty
      nine asphyxiated infants were studied with serial neurologic examination, cranial
      ultrasonography, and neurologic follow-up. CSF samples were obtained by lumbar
      puncture at 12 and 72 hours of life. NSE was measured by enzyme immunoassay, and
      MBP was measured by radioimmunoassay. RESULTS: Twenty infants had no neonatal
      encephalopathy and 49 exhibited different stages of encephalopathy. NSE and MBP
      concentrations in CSF at 12 and 72 hours of life were related to the degree of
      neonatal encephalopathy. Neither NSE nor MBP levels were correlated with any
      perinatal factors. Infants with documented brain injury had the highest
      concentrations of both NSE and MBP. The concentrations of these two biochemical
      markers at both 12 and 72 hours correlated with adverse outcome (death or
      cerebral palsy at 1 year). Based on a receiver operating characteristics curve
      analysis for any given specificity, NSE at 12 hours was a more accurate marker
      than MBP at either 12 or 72 hours for distinguishing infants with motor
      impairment at age 1 year from infants with normal outcome at the same age.
      CONCLUSIONS: Our findings suggest that NSE and MBP are reliable biochemical
      markers for early estimates of hypoxic-ischemic brain damage in asphyctic full
      term newborns, NSE being superior to MBP.

PMID- 7510065
TI  - Premature strand transfer by the HIV-1 reverse transcriptase during strong-stop
      DNA synthesis.
AB  - Reverse transcription of retroviral genomes starts near the 5' end of the viral
      RNA by use of an associated tRNA primer. According to the current model of
      reverse transcription, the initial cDNA product, termed minus-strand strong-stop
      DNA, 'jumps' to a repeated sequence (R region) at the 3' end of the RNA template.
      The human retroviruses have relatively long R regions (97-247 nucleotides) when
      compared to murine and avian viruses (16-68 nucleotides). This suggests that the
      full complement of the R region is not required for strand transfer and that
      partial cDNA copies of the 5' R can prematurely jump to the 3' R. To test this
      hypothesis, we generated mutants of the human immunodeficiency virus with R
      region changes and analyzed whether 5' or 3' R sequences were inherited by the
      progeny. We found that in most cases, 5' R-encoded sequences are dominant, which
      is consistent with the model of reverse transcription. Using a selection
      protocol, however, we were also able to identify progeny viruses with R sequences
      derived from the original 3' R element. These results suggest that partial strong
      stop cDNAs can be transferred with R region homologies much shorter than 97
      nucleotides.

PMID- 7510066
TI  - [Cytokeratins in inverted papillomas of the urinary bladder. (Part 1.)].
AB  - Inverted papilloma (transitional cell papilloma, inverted type) is a rare, benign
      urothelial tumor. The distribution of cytokeratin (CK) expression in 22 cases was
      investigated and compared with normal urothelium and urothelial carcinomas:
      CK7/8, basal increased positivity; CK13, diffuse positivity; CK18, loss of
      intensity and loss of umbrella cell staining; CK19, reduction of positivity;
      CK20, reduction of umbrella cell staining. The data indicate that the inverted
      papilloma is a basal cell urothelioma.

PMID- 7510067
TI  - [Diagnosis and differential diagnosis of sialo-odontogenic (glandular
      odontogenic) cyst].
AB  - Sialo-odontogenic (glandular-odontogenic) cyst is a new entity in the
      classification of developmental epithelial odontogenic cysts. Differentiation of
      this type of odontogenic cysts from dentigerous cysts and keratocysts and also
      from cystic mucoepidermoid carcinoma is essential. A sialo-odontogenic (glandular
      odontogenic) cyst is likely to show aggressive growth, so that complete resection
      is essential. We demonstrate sialo-odontogenic (glandular-odontogenic) cyst by
      presenting four new cases and differentiate it from a special type of odontogenic
      keratocyst and a typical cystic mucoepidermoid carcinoma.

PMID- 7510071
TI  - [The organization of care and the accompaniment of the patients in the terminal
      phase].

PMID- 7510068
TI  - [Adhesion molecules in inflammatory rheumatisms].

PMID- 7510069
TI  - Diversity of endogenous epitopes bound to MHC class II molecules limited by
      invariant chain.
AB  - The invariant chain (Ii) binds nascent major histocompatibility complex (MHC)
      class II molecules, blocking peptide binding until the complex dissociates in the
      endosomes. This may serve to differentiate the MHC class I and II antigen
      presentation pathways and enable class II molecules to efficiently bind peptides
      in the endosomes. This hypothesis was addressed by probing spleen cells from a
      combination of knock-out and transgenic mice with a large panel of T cell
      hybridomas. The Ii molecule blocked the presentation of a range of endogenously
      synthesized epitopes, but some epitopes actually required Ii. Thus, the influence
      of Ii on presentation does not follow simple rules. In addition, mice expressing
      Ii were not tolerant to epitopes unmasked in its absence, a finding with possible
      implications for autoimmunity.

PMID- 7510070
TI  - Fludarabine phosphate: a new active agent in hematologic malignancies.

PMID- 7510072
TI  - Squamous cell carcinoma of the oesophagus--an unusual presentation with malignant
      ascites. A case report.
AB  - A 58-year-old black woman was admitted to hospital with abdominal pain and gross
      ascites and was found on examination to have a tumour in the pouch of Douglas and
      subsequently to have squamous carcinoma of the oesophagus. The patient was
      treated non-operatively by repeated ascitic taps and intubation of the
      oesophagus.

PMID- 7510073
TI  - [Clinical significance of prostate-specific antigen].
AB  - Prostate-specific antigen has replaced acid phosphatase as a more sensitive
      marker of prostatic cancer. It is organ-specific but not cancer-specific.
      However, high serum level is more often indicative of cancer than of benign
      hyperplasia. The authors discuss the value of prostate-specific antigen in
      diagnosis and prognosis, and the indications for its use. This test should be
      included in the examination of men with prostatic symptoms and in men below age
      70-75 with a suspicious finding in the prostate on digital rectal examination. At
      present, we do not recommend it for screening purposes, except in men with a
      family history of cancer of the prostate gland.

PMID- 7510074
TI  - [Open readmission. A service to patients with incurable cancer].
AB  - The Open readmission programme is a service to patients with incurable cancer. It
      allows the patients and their family to contact our department at any time if
      medical assistance is needed. Each patient is allocated a primary nurse who has
      the main responsibility for his on her particular case. The nurse has been
      delegated the responsibility to evaluate the need for admission to hospital, and
      to arrange it. If acute hospitalization is needed a nurse at the department is
      contacted and an ambulance is sent. The patient is admitted without any primary
      examination by an emergency service unit or a practising physician. The patients
      are not delayed in the emergency room, but are directly transferred to a clinical
      ward. The nurses are responsible for administering the programme, and the
      physician notes the admission in the medical records. The Open readmission
      programme has been a success in the way it has been practised at our department,
      and meets the needs of patients and relatives for greater security and confidence
      that they will receive help.

PMID- 7510075
TI  - [Miracles in medicine. Attempt to an analysis].

PMID- 7510079
TI  - Ion channels and their associated currents: thoughts on a standardized
      nomenclature.

PMID- 7510078
TI  - Computer-guided concentration-controlled trials in autoimmune disorders.
AB  - A randomized concentration-controlled clinical trial (RCCCT) is an alternate
      experimental design to the standard dose-controlled study. In a RCCCT, patients
      are randomly assigned to predefined plasma or blood drug concentration ranges
      (low, medium, and high). With the caveat that concentration ranges are
      sufficiently separated, this design should enhance the ability to discover
      important concentration response relationships. FK-506, a potent and promising
      immunosuppressive agent for prevention and treatment of graft rejection, has
      shown significant clinical activity in some immune-mediated disorders. To
      implement the RCCCT design, a novel FK-506 intelligent dosing system (IDS) was
      used to guide all doses to prospectively achieve the target concentration range
      specific in the study protocol. Patients enrolled in these trials suffered from a
      variety of autoimmune disorders, including multiple sclerosis, primary biliary
      cirrhosis, psoriasis, autoimmune chronic active hepatitis, and nephrotic
      syndrome. We observed excellent predictive performance of the IDS for all
      patients. The accuracy (mean prediction error) of the IDS was -0.022 ng/ml and
      the precision (standard deviation of the prediction error) was 0.119 ng/ml. Thus,
      the IDS is both accurate and reproducible for autoimmune patients. We conclude
      that the RCCCT design, guided by an accurate and precise IDS, is an informative
      and cost-effective approach for evaluation of efficacy and safety of effective
      but highly toxic agents.

PMID- 7510076
TI  - Morphological analysis of yolk sac tumor.
AB  - Morphological analysis of imprint histology and cytology was performed in 7
      patients with yolk sac tumor (YST). As a result, histological figures of YST were
      classified into 4 patterns. Endodermal sinus pattern was most frequently
      identified, followed by polyvesicular vitelline pattern. Imprint cytology
      findings of YST were also classified into 4 patterns. Cuboidal cells were most
      frequently observed; cells and nuclei were both cuboidal in shape and 25-40 mu
      and 20-25 mu in diameters, respectively. The chromatic showed fine to coarse
      granular patterns. The nuclear cytoplasmic (N/C) ratio was 50-70%, and each
      nucleus contained one to four nucleoli. Next to cuboidal cells, spindle-shaped
      cells were frequently noticed; 20-40 mu in size with spindle-shaped nuclei 10-20
      mu in diameter and fine to coarse granular chromatic pattern. Naked cells and
      bizarre cells were also noticed. It was postulated that cuboidal cells and
      spindle-shaped cells were originated from the endodermal sinus pattern and the
      loose reticular pattern of YST, respectively. When utilized with rapid-frozen
      specimens, imprint cytology of YST is sufficient for rapid diagnosis during
      operations.

PMID- 7510080
TI  - Anti-inflammatory actions of steroids: molecular mechanisms.
AB  - Glucocorticosteroids are highly effective in controlling inflammation and the
      molecular mechanisms involved are now becoming clear. Activation of
      glucocorticoid receptors results in increased or decreased transcription of a
      number of genes involved in the inflammatory process. Of particular importance is
      the repression of cytokine gene transcription and the direct interaction between
      the glucocorticoid receptor and other transcription factors activated in chronic
      inflammation. In this review, Peter Barnes and Ian Adcock discuss recent studies
      that have increased our understanding of these mechanisms and that may lead to
      improved anti-inflammatory therapies in the future.

PMID- 7510077
TI  - Immunophilin receptors for immunosuppressive drugs.
AB  - The major immunophilins that bind cyclosporine (cyclophilin) and FK-506/rapamycin
      (FK-BP 12) have been well characterized. They possess rotamase activity, which is
      inhibited by the immunosuppressant that binds to them. The immunosuppressive
      action does not appear to be coupled to rotamase activity. The literature is
      reviewed on some possible mechanisms of immunosuppression. Minor immunophilins of
      14, 36, and 52 kDa have also been isolated and partially characterized. Receptor
      assays employing immunophilins have been developed.

PMID- 7510081
TI  - Conformationally sensitive antigenic determinants on the HN glycoprotein of
      Newcastle disease virus form with different kinetics.
AB  - The mature Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) protein
      is a type 2, oligomeric glycoprotein which has seven antigenic sites, sites 1, 2,
      3, 4, 23, 12, and 14 (lorio et al., 1989, Virus Res. 13, 245). The folding of the
      HN protein was explored by characterizing the formation of representative
      epitopes specific for each of the six of antigenic sites in infected cells. None
      of these epitopes was present on the nascent, 5-min pulse-labeled HN protein,
      while all epitopes appeared after a 1- to 2-hr chase. All epitopes formed in the
      presence of monensin or during a chase at 15 degrees, suggesting that all these
      determinants appear while the molecule is in the rough endoplasmic reticulum.
      However, none of the epitopes appeared during chases in the presence of carbonyl
      cyanide m-chlorophenylhydrazone, suggesting that the formation of all
      determinants requires ATP. The kinetics of formation of each of the determinants
      was quantitated in both NDV-infected Cos cells and chick embryo cells. In both
      cell types, antigenic determinants formed with different kinetics. The epitope
      specific for site 4 appeared first, followed by the simultaneous appearance of
      epitopes in sites 1 and 3. The epitope in site 2 appeared next and that in site
      23 last. The kinetics of appearance of the epitope in site 14 relative to those
      in other sites varied with cell type. In chick cells, this epitope appeared with
      the site 2 epitope, while in Cos cells this epitope appeared with or just after
      sites 1 and 3 epitopes. Nonradioactive chases at 15 degrees slowed the formation
      of the antigenic determinants. The disulfide-linked dimer form of the HN protein
      appeared concomitant with epitopes in sites 1 and 3.

PMID- 7510083
TI  - Fidelity of HIV-1 reverse transcriptase copying a hypervariable region of the HIV
      1 env gene.
AB  - The unusually high mutation frequency exhibited by the human immunodeficiency
      virus (HIV) is a major impediment to developing effective vaccines against the
      virus and to designing analogs that inhibit viral replication. To investigate the
      molecular basis of HIV hypermutability, we established cell-free assays to
      measure the fidelity of HIV-1 reverse transcriptase (RT) in copying either DNA or
      both RNA and DNA templates that contain the hypervariable region 1 of the HIV-1
      env gene (V-1). The fidelity of DNA synthesis was measured by repetitively
      copying the envelope gene (V-1) DNA by HIV-1 RT, followed by cloning and
      sequencing these newly synthesized DNA products. We found that the error rate of
      HIV RT copying either RNA or DNA of the env V-1 region is about one
      misincorporation per 5 kb polymerized. This rate is similar to that found with
      the M13mp2 forward mutation assay using the lacZ alpha gene as a template. This
      similarity suggests that the HIV env hypervariable sequence is not inherently
      hypermutable. The high error rate of HIV RT suggests that misincorporation by
      this enzyme is a major source of mutations throughout the viral genome and a
      determinant for rapid viral evolution. The spectrum of mutations produced by HIV
      RT in vitro partially correlates with the spectrum of HIV mutations observed in
      AIDS patients. The differences between these spectra highlight the contribution
      of phenotypic selection during HIV-1 infection. The overall uniformity of
      misincorporation of HIV-1 RT further suggests an alternative anti-HIV strategy
      based on increasing viral mutagenesis by nucleotide analogs.

PMID- 7510084
TI  - Common sequence elements in structurally unrelated genomes of defective
      interfering Semliki Forest virus.
AB  - The polymerase chain reaction was used to amplify defective interfering (DI)
      Semliki Forest virus (SFV) genomes from tissue culture preparations which had in
      vitro interfering and in vivo mouse-protecting activity. The products were
      molecularly cloned and sequenced (pSFVDI-6, 2146 nt and pSFVDI-19, 1244 nt).
      Comparison with the sequence of the SFV genome showed that both were derived from
      three noncontiguous regions: the 5' terminus including the start of the nsP1
      coding region, part of the nsP2 coding region, and the 3' untranslated region.
      Both clones possessed open reading frames, including one with the potential of
      encoding truncated versions of nsP1. Transcribed RNAs from pSFVDI-6 and pSFVDI-19
      were translated in an in vitro system in polypeptides of M(r) 27,000 and 25,000,
      respectively. Although pSFVDI-6 and pSFVDI-19 did not possess the rearranged
      sequences or extensive repeat regions of previously cloned DI SFV genomes
      (Lehtovaara et al., Proc. Natl. Acad. Sci. USA 78, 5353-5357, 1981; Lehtovaara et
      al., J. Mol. Biol. 156, 731-748, 1982), they were derived from similar regions of
      the SFV genome, suggesting a common sequence requirement for DI SFV particles.

PMID- 7510082
TI  - Use of HPV 1 capsids produced by recombinant vaccinia viruses in an ELISA to
      detect serum antibodies in people with foot warts.
AB  - A sandwich ELISA was developed to detect HPV antibodies using HPV 1 capsids that
      were purified from recombinant vaccinia virus-infected cells and a monoclonal
      antibody to the HPV 1 L1 protein. Sera from 91 college-aged women who had been
      previously screened for HPV 1 antibodies by immune precipitation of capsid
      proteins were tested by ELISA. A cutoff point was established independently of
      other criteria based on the assumption that the ELISA values came from a mixture
      of two Normal distributions representing seropositive and seronegative
      individuals. It was found that the data fit this model best when the natural log
      of the ELISA (+0.5 to make all of the values positive) was used. Positive sera
      were shown to react with a conformational epitope(s) on the L1 protein. In the
      population reporting foot warts, 16 of 18 (89%) had ELISA values above the
      cutoff. This compared to 38 of 73 (53%) positives in the population reporting no
      history of foot warts. The odds ratio for the association of the ELISA reactivity
      with foot warts was 7.23 (95% CI 1.53, 69.4; P < 0.01). There was no significant
      association between the ELISA reactivity and wart infections reported at other
      sites. The average of the log ELISA values for individuals never reporting foot
      warts was -0.223 (SD 0.468), whereas the average value for individuals reporting
      foot warts within 10 years was 0.191 (SD 0.450) (P = 0.001). There was a negative
      correlation between the magnitude of ELISA reactivity and the time elapsed since
      the last appearance of foot warts. This apparent loss of seroreactivity over time
      may indicate that HPV 1 is usually eliminated from the host after infection or
      that inadequate levels of HPV 1 capsid antigen are produced during latent foot
      warts to maintain antibody levels.

PMID- 7510085
TI  - Viral cross-reactivity and antigenic determinants recognized by human
      parainfluenza virus type 1-specific cytotoxic T-cells.
AB  - To obtain information relevant to vaccination against human parainfluenza virus
      type 1 (hPIV-1), cytotoxic T-lymphocyte (CTL) responses to individual viral
      components were tested. The CD8-positive T-cell fraction was first enriched from
      human, adult PBL and grown for several passages in the presence of hPIV-1
      infected stimulator cells. T-cell lines were then tested for CTL activity toward
      hPIV-1 and toward the related viruses hPIV-3 and Sendai virus (the murine
      parainfluenza type 1 virus). All tested cultures which responded to hPIV-1 also
      responded to hPIV-3 and Sendai virus, demonstrating sequence conservation between
      all three viruses among major antigenic determinants for CTL. Specificity for
      particular viral components was defined using recombinant vaccinia viruses
      expressing individual proteins from either mouse or human parainfluenza type 1
      viruses. Strong CTL responses toward hemagglutinin-neuraminidase, phosphoprotein,
      and nucleoprotein (NP) were demonstrated. The testing of vaccinia constructs
      expressing truncated proteins then showed that there were multiple CTL
      determinants within NP. Several T-cell lines from one donor recognized an NP
      peptide (amino acids 321-336) conserved between the hPIV-1 and Sendai virus. In
      total, the results demonstrated that the human CTL response is directed to
      multiple determinants within several distinct hPIV-1 proteins.

PMID- 7510087
TI  - The interferon-induced double-stranded RNA-activated protein kinase induces
      apoptosis.
AB  - Interferons (IFNs) exert antitumor activities, but the molecular mechanism
      underlying these effects is poorly understood. IFN-induced, double-stranded (ds)
      RNA-activated protein kinase (p68 kinase) has long been implicated in mediating
      the antiproliferative effects of IFN. In addition, recent studies suggest that
      p68 kinase may function as a tumor suppressor gene. In this investigation we
      showed that expression of p68 kinase in HeLa cells resulted in a rapid cell death
      characteristic of apoptosis. Rapid cell death was not observed in cells which
      expressed a mutant form of p68 kinase (lys296-->arg) indicating that cell death
      observed is the result of p68 kinase expression and activation. Moreover,
      infection of HeLa cells with the mutant vaccinia virus lacking E3L gene, which
      encodes a dsRNA binding protein that acts as an inhibitor of p68 kinase, also
      resulted in apoptosis. Thus, we propose that human p68 kinase functions as a
      tumor suppressor gene by actively participating in apoptosis.

PMID- 7510086
TI  - Neutralization epitope of the varicella-zoster virus gH:gL glycoprotein complex.
AB  - Varicella-zoster virus (VZV) glycoprotein gpIII is the homolog of herpes simplex
      virus gH. Through the use of panels of monoclonal antibodies, VZV gpIII is known
      to possess a complement-independent neutralization epitope which is
      conformational in nature. Monoclonal antibody to this same epitope, when added
      postinfection, inhibits both syncytia formation and egress of virus. The nature
      of the neutralization epitope was investigated to determine whether its formation
      was dependent on gpIII alone or required a second VZV glycoprotein. To this end,
      VZV ORF 37 (gH) and VZV ORF 60 (gL homolog) were cloned into a vaccinia virus
      pTM1 expression system. Analyses of the transfected products demonstrated that
      gpIII alone was not fully glycosylated nor was it transported to the cell
      surface. When both ORF 37 and ORF 60 were cotransfected, the gpIII product was
      transported to the cell surface, where it formed a neutralization epitope
      recognized by a previously characterized monoclonal antibody reagent. In summary,
      the VZV homologs of the herpes simplex virus gH:gL complex included a M(r)
      118,000 product (gpIII or gH) and a M(r) 20,000 product (ORF 60 or gL).

PMID- 7510089
TI  - [Genetic mutation of hepatitis C virus and host's immune response].

PMID- 7510090
TI  - [Donors blood screening and prevention of posttransfusion type C hepatitis in
      Japan].

PMID- 7510091
TI  - [Natural history and treatment of type C hepatitis].

PMID- 7510092
TI  - [Mother-to-infant transmission of hepatitis C virus].

PMID- 7510093
TI  - [Pediatric dysphasia. 1. The concept and clinical aspects].
AB  - This survey deals with the early diagnosis and treatment of children with
      developmental dysphasia, which may prevent the progression of learning and
      behavior disorders. In the pre-verbal and early verbal stage, the severity of the
      clinical picture is primarily determined by concomitant motor pathology (motor
      dysfunction, dysarthria, general and oral dyspraxia) and by receptive pathology
      (hearing and auditory perception). In the verbal period, linguistic problems
      start to play a role, and often combine with oral motor symptoms to present a
      mixed picture. Various language syndromes do not become clear until some time
      later. After the kindergarten period, the oral motor and perceptual problems
      decrease and the language disorders continue to play a role and influence the
      child's conversation, internal speech reading and spelling at school. In a
      relatively small number of children without oral motor, perceptual or memory
      problems, there can be a basic syndrome of "pure dysphasia" without any other
      neurological signs. In somewhat more than half the patients, the basic syndrome
      of pure dysphasia is accompanied by other neurological signs. Treatment should
      not be confined to speech therapy techniques, but can only be optimally given by
      a highly trained team whose expertise also extends to the schooling aspect.

PMID- 7510094
TI  - Fetal sex and maternal alpha-fetoprotein concentration at late normal singleton
      pregnancies.
AB  - The aim of this study is to investigate maternal and fetal clinical parameters on
      maternal serum alpha-fetoprotein (MAFP) levels at late pregnancies. The studied
      subjects were 36 to 40 weeks pregnant. The pregnancies were singletons without
      any medical or gynecologic disease. Delivery followed within three days after
      blood sampling. A total of 192 subjects were included. The MAFP levels were
      measured by radioimmunoassay. The results showed the average MAFP was 108.2 ng/ml
      (SE 4.8 ng/ml). Male-fetus-bearers had higher MAFP (mean 121.4, SE 8.2 ng/ml, n =
      84) than female-fetus-bearers (mean 97.9, SE 5.43 ng/ml, n = 108) (p = 0.014).
      MAFP did not have significant correlation with fetal weight (p > 0.05) regardless
      of whether the fetus was a male (p > 0.05) or female (p > 0.05). By stepwise
      multiple regression, fetal sex was revealed to be the only factor that can affect
      MAFP (p = 0.0071). MAFP did not correlate with maternal age, gravidity, parity,
      maternal weight, total weight gain during pregnancy, gestational weeks, or fetal
      weight (all p > 0.05). Since fetal sex is the only factor that influences MAFP
      levels at uncomplicated late pregnancies, MAFP values should be interpreted with
      caution.

PMID- 7510095
TI  - Cytokines and growth factors in the regulation of bone remodeling.
AB  - Osteoporosis and periodontal disease both represent examples of abnormal bone
      remodeling. As knowledge of the cellular and molecular events in the normal bone
      remodeling process has accumulated in the last decade, better understanding of
      the pathophysiology of bone loss associated with periodontal disease and with
      aging has occurred. This short review does not attempt to include all aspects of
      this topic but covers specific areas in which there have been recent advances.
      (1) Observations made in the last few years have indicated that a hierarchy of
      both receptor and nonreceptor tyrosine kinases may be involved in normal
      osteoclastic bone resorption and that certain members of these tyrosine kinase
      families may mediate cytokine effects. Studies in the op/op variant of murine
      osteopetrosis have shown that normal production of monocyte-macrophage colony
      stimulating factor 1 (M-CSF, also called CSF-1) and activation of its receptor
      (the receptor tyrosine kinase c-fms) are required for normal osteoclast
      formation. (2) Studies in mice made deficient in nonreceptor tyrosine kinase by
      gene knockout have shown that expression of this nonreceptor tyrosine kinase is
      required for normal osteoclast action and ruffled border formation, although not
      for osteoclast formation. (3) Recent studies have shown that in addition to
      prostaglandins of the E series, other arachidonic acid metabolites may be
      involved in normal and abnormal osteoclastic bone resorption. 5-Lipoxygenase
      metabolites, the leukotrienes, stimulate isolated osteoclasts to form resorption
      pits as well as cause osteoclastic bone resorption in organ cultures of neonatal
      mouse calvariae. These compounds, which are unstable in tissue culture media, are
      readily inhibitable by agents that inhibit 5-lipoxygenase enzymes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7510088
TI  - [Structural proteins of hepatitis C virus].

PMID- 7510096
TI  - Distribution of substance P immunoreactive nerve fibers in the tracheal
      submucosal gland of cats.
AB  - Immunohistochemistry combined with electron microscopy was employed to
      investigate the distribution of substance P-immunoreactive (SP-IR) nerve fibers
      in the tracheal submucosal gland of cats. The SP-IR nerve fibers were found to
      form a network around the glands. Numerous varicosities were also detected within
      the basement membrane of the acini and secretory tubules. All the intraglandular
      varicosities showed close spatial contact with serous cells, mucous cells, and
      myoepithelial cells. Our findings suggest that substance P-induced mucus
      secretion from tracheal submucosal glands in cats may be caused not only by a
      glandular contractile response of myoepithelial cells, but also by direct
      stimulation to both serous and mucous cells.

PMID- 7510097
TI  - Cytokeratin patterns of normal middle ear epithelia in humans, cats, and
      chinchillas.
AB  - We describe the cytokeratin patterns of epithelia from the tympanic orifice,
      tympanic cavity, and mastoid cavity of humans, cats, and chinchillas, and compare
      these findings with those of tracheal epithelium and external canal epidermis.
      Our findings are as follows: 1) middle ear epithelium from all locations
      demonstrates some type of cytokeratin staining, 2) broad-spectrum cytokeratin
      antibodies stain epithelia of middle ear cleft, tracheal epithelium, and external
      canal epidermis in all species, 3) specific cytokeratin antibodies reveal species
      related differences in middle ear and tracheal epithelia, 4) middle ear and
      tracheal epithelia usually have the same pattern, and 5) none of the monospecific
      cytokeratin antibodies have a positive reaction with external canal epidermis.
      These findings suggest that the cytokeratin patterns of middle ear epithelium are
      useful in studying the hyperplastic and metaplastic changes in otitis media;
      however, caution must be exercised when making interspecies comparisons.

PMID- 7510098
TI  - Anti-myelin basic protein and anti-proteolipid protein specific forms of multiple
      sclerosis.
AB  - Human myelin basic protein (hMBP) and proteolipid protein (PLP) were used as
      antigens in a solid-phase radioimmunoassay to determine relative frequencies of
      anti-MBP and anti-PLP in cerebrospinal fluid (CSF) of optic neuritis and multiple
      sclerosis (MS) patients. Forty-nine of 55 patients with optic neuritis had
      increased CSF anti-MBP and the remaining 6 had increased anti-PLP. Of 385 MS
      patients, MS relapse: 173 of 180 patients had increased anti-MBP, 5 of the
      remaining 7 patients had elevated anti-PLP, and 2 had neither of these
      autoantibodies. Progressive MS: 111 of 116 patients had increased anti-MBP in
      either free and/or bound form, of the remaining 5 patients 4 had increased anti
      PLP, and 1 had neither anti-MBP nor anti-PLP. MS remission: 15 of 87 patients had
      somewhat increased anti-MBP, none had anti-PLP. IgG was purified by affinity
      chromatography from necropsy central nervous system (CNS) tissue samples of 4
      individual patients with clinically definite and neuropathologically confirmed
      MS. Three of these 4 patients who had increased levels of CSF anti-MBP also had
      increased anti-MBP titers in CNS tissue-extracted IgG. The fourth patient who had
      anti-PLP in CSF also had anti-PLP in brain tissue IgG. These autoantibodies were
      not detected simultaneously in any patient. These results suggest that there are
      at least two immunologically distinct forms of MS, i.e., a common form highly
      associated with anti-MBP and more frequent prominent inflammatory characteristics
      in CSF and CNS, and an infrequent form associated with anti-PLP in CSF and
      tissue, and less abundant inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510102
TI  - 1-Aryl-2-amino/hydrazino-4-phenyl-1,6-dihydro-1,3,5-triazine-6-thione and related
      thiocarbamides/thiosemicarbazides as antithyroidal agents.
AB  - Different 1-aryl-2-benzylmercapto-4-phenyl-1,6-dihydro-1,3,5-triazine-6- thiones
      have been synthesized by known methods. These triazines on treatment with
      ammonia/hydrazine hydrate afforded the corresponding 1-aryl-2-amino/hydrazino-4
      phenyl-1,6-dihydro-1,3,5-triazine-6-thiones which on treatment with
      arylisothiocyanates afforded the related thiocarbamide/thiosemicarbazides. Some
      of these compounds show appreciable antithyroidal activity.

PMID- 7510100
TI  - The role of nitric oxide in parasitic diseases.
AB  - Murine macrophages express high levels of nitric oxide synthase and produce large
      amounts of nitric oxide (NO) when stimulated with certain cytokines in the
      presence of a trace amount of lipopolysaccharide (LPS). The stimulatory cytokines
      include interleukin-1 (IL-1), interferon-gamma (IFN-gamma), tumour necrosis
      factor-alpha (TNF-alpha) and migration inhibitory factor. Activated macrophages
      are highly effective killers of intra- and extra-cellular pathogens. However, as
      excessive NO can lead to immunopathology (diabetes, graft-v.-host disease, EAE,
      liver cirrhosis, rheumatoid arthritis), NO production is necessarily under tight
      regulation. A number of cytokines, including IL-4, IL-10 and transforming growth
      factor-beta, can down regulate the induction of NO synthase in macrophages. In
      addition, macrophages exposed to LPS alone and then stimulated with a mix of IFN
      gamma and LPS express significantly lower levels of NO synthase than cells
      stimulated without pre-exposure to LPS. Furthermore, NO can reduce the activity
      of NO synthase by feedback inhibition, and also inhibit the production of IFN
      gamma by Th1 cells (thus turning off its own synthesis from upstream). The
      regulatory pathways involve tyrosine kinase and protein kinase C.

PMID- 7510099
TI  - Oligodendrocyte lysis by CD4+ T cells independent of tumor necrosis factor.
AB  - The capacity of human CD4+ T cells to lyse heterologous human oligodendrocytes in
      an 18-hour chromium 51-release assay was compared to that of systemic blood
      derived macrophages and central nervous system-derived microglia. CD4+ T cells,
      activated with either phytohemagglutinin, anti-CD3 antibody, or antigen (myelin
      basic protein), could induce lysis of the oligodendrocytes whereas macrophages
      and microglia, activated with interferon-gamma and lipopolysaccharide, could not.
      The CD4+ T-cell effect was not inhibited with an anti-tumor necrosis factor-alpha
      neutralizing antibody. Both the CD4+ T cells and the macrophages could induce
      lysis of tumor necrosis factor-sensitive rodent cell lines, Wehi 164, and L929;
      these effects were inhibited with anti-tumor necrosis factor antibody.
      Pretreatment of the CD4+ T cells with cyclosporine or mitomycin C did not inhibit
      oligodendrocyte lysis. These results indicate that at least in vitro, CD4+ T
      cells can induce a form of oligodendrocyte injury that is not reproduced by
      macrophages or microglia or by tumor necrosis factor. The non-major
      histocompatibility complex (MHC)-restricted injury of oligodendrocytes induced by
      both myelin antigen-reactive and mitogen-stimulated T cells may provide a basis
      whereby cytotoxic CD4+ T cells could interact with a target cell that does not
      express MHC class II molecules. Our results suggest that immune-mediated
      oligodendrocyte/myelin injury, as is postulated to occur in the disease multiple
      sclerosis, may involve multiple effector mechanisms.

PMID- 7510101
TI  - Adnexal gland secretion markers in unexplained asthenozoospermia.
AB  - Prostatic acid phosphatase, prostate-specific antigen, and zinc as markers of
      prostate, and fructose as marker of seminal vesicles were investigated in the
      seminal plasma of 35 idiopathic asthenozoospermic and 20 normal subjects to
      evaluate their relationship with sperm motility. Total seminal plasma levels of
      the three prostatic markers and, to a lesser extent, total fructose levels were
      lower in asthenozoospermic patients, and in all the pooled subjects, the same
      levels were directly correlated with the motility of ejaculated spermatozoa. When
      the levels of the biochemical markers were expressed as concentrations in seminal
      plasma, only prostatic acid phosphatase levels remained lower in
      asthenozoospermic patients and they maintained a direct correlation with sperm
      motility in all the pooled subjects. The PAP/Zn/Fr (representing the ratio
      between PAP concentration and free Zn available for spermatozoan uptake) was
      lower in asthenozoospermic patients and it was also directly related to sperm
      motility in all the pooled subjects. These data suggest that altered sperm
      motility is associated with a probable impairment of sex accessory gland function
      in subjects with idiopathic asthenozoospermia, while prostatic acid phosphatase
      seems mainly related to sperm motility.

PMID- 7510104
TI  - Effects of NG-methyl-L-arginine, NG-nitro-L-arginine, and aminoguanidine on
      constitutive and inducible nitric oxide synthase in rat aorta.
AB  - A new selective inhibitor of the inducible nitric oxide synthase in the treatment
      of pathogenesis characterized by overproduction of nitric oxide may be useful.
      Therefore, we have examined the effects of two L-arginine analogues, NG-methyl-L
      arginine (L-NMA) and NG-nitro-L-arginine (L-NNA), and aminoguanidine (AG) on the
      constitutive and inducible nitric oxide synthase in rat aorta. L-NNA induced
      greater contractions to phenylephrine than L-NMA whereas AG had no effect on dose
      response curves to this alpha 1-agonist in rat aorta with endothelium.
      Relaxations to acetylcholine, adenosine triphosphate, and A 23187 were fully
      abolished by L-NNA, while L-NMA partially inhibited and AG did not affect the
      relaxations to these three vasodilators. L-NNA, L-NMA, and AG were equipotent in
      inhibiting the vascular hyporeactivity to phenylephrine induced by endotoxin in
      rat aortic rings with endothelium; however, the rate of onset of the maximum
      inhibitory effects of AG was slower than that obtained with L-NNA and L-NMA. L
      arginine completely abolished the effects of AG, but only partially reversed the
      effects of L-NNA and L-NMA in LPS-treated rings. These results suggest that AG
      selectively inhibits inducible nitric oxide synthase, whereas L-NNA and L-NMA
      exert their effects on both the constitutive and inducible nitric oxide synthase.

PMID- 7510103
TI  - A novel ancestral protein of Drosophila alcohol dehydrogenase in Streptomyces?
AB  - Polyclonal antibodies raised against purified Drosophila alcohol dehydrogenase
      (ADH) were used in Western blot analyses to search for structurally and/or
      immunologically related proteins in prokaryotes and eukaryotes. No immunological
      reactive protein was detected in a flesh fly, a locust, and butterflies.
      Immunological similarity with the 50-kDa PQQ-glucose dehydrogenase (GluDH)-B
      enzyme of Acinetobacter calcoaceticus was found, but the cross-reactivity
      apparently is dependent on the high hydrophilic character of this protein.
      Antibodies against PQQ-GluDH did not recognize Drosophila ADH. In five of seven
      species of the gram-positive soil bacteria actinomycetes tested, a protein
      approximately 28-30 kDa in subunit size was strongly recognized by alpha-DADH. It
      is probably not one of the two proteins with known homology to Drosophila ADH,
      viz., the actIII gene product and 20 beta-hydroxysteroid dehydrogenase. The
      protein is present in both the soluble and the pellet-membrane fraction of the
      cells. The protein has a late temporal expression in surface-grown cultures and,
      therefore, might be involved in secondary metabolism.

PMID- 7510105
TI  - Molecular cloning and characterization of G-CSF induced gene cDNA.
AB  - G-CSF (granulocyte colony-stimulating factor) is known to specifically stimulate
      the production and the functional activation of neutrophils. To investigate the
      intracellular signaling pathway of myeloid cells stimulated by G-CSF, we isolated
      new genes whose expression was induced by G-CSF. First of all, we constructed
      lambda gt10 cDNA library from G-CSF-stimulated mononuclear cells (MNC) of a
      chronic myelogenous leukemia (CML) patient (CML-MNC) and screened the cDNA
      library by a differential hybridization method. The 24 candidate clones which
      specifically hybridized with G-CSF-stimulated CML-MNC cDNA probes, but not with
      unstimulated CML-MNC cDNA probes, were obtained after 8 x 10(4) individual clones
      had been screened. One of these clones, GIG-1 (G-CSF-induced gene-1), was further
      characterized. The size of the GIG-1 mRNA was about 0.9kb. The GIG-1 mRNA was
      expressed mainly in the myeloid leukemic cell lines.

PMID- 7510106
TI  - Activation of macrophage PtdIns-PLC by phorbol ester and vanadate: involvement of
      reactive oxygen species and tyrosine phosphorylation.
AB  - Phorbol ester (TPA) is generally considered to be a negative regulator of PtdIns
      PLC activity. Here we show, for the first time, that the combination of TPA+
      vanadate is a positive regulator (activator) of PtdIns-PLC in mouse elicited
      peritoneal macrophages. Vanadate or TPA on their own had no effect on PtdIns-PLC
      activity. In addition, TPA+ vanadate enhanced reactive oxygen species formation
      and protein tyrosine phosphorylation. PtdIns-PLC activation was suppressed by
      down regulation or inhibition of PKC, by inhibition of NADPH oxidase activity and
      scavenging of its product, and by inhibitors of protein tyrosine kinase activity.
      We conclude that PKC activation by TPA in the presence of vanadate activates the
      formation of reactive oxygen species, which are essential for the enhancement of
      protein tyrosine phosphorylation and eventually to PtdIns-PLC activation.

PMID- 7510107
TI  - Ethanol impairs insulin receptor substrate-1 mediated signal transduction during
      rat liver regeneration.
AB  - Chronic ethanol exposure inhibits the capacity of the liver to regenerate.
      Insulin is a potent hepatotrophic factor and it was determined if ethanol
      interferes with insulin receptor substrate (IRS-1)-protein mediated signal
      transduction during liver regeneration. Tyrosyl phosphorylation of IRS-1 was
      strikingly increased prior to the major wave of DNA synthesis in isocaloric pair
      fed control rats; a blunted and delayed response was found in ethanol-fed rats.
      Enzymatic activity of phosphatidylinositol 3-kinase, a Src homology 2 (SH2)
      domain containing signal transduction molecule was enhanced by the association
      with tyrosyl phosphorylated IRS-1, whereas in ethanol-fed rats, this activity was
      greatly diminished and delayed. These results indicate that one potential
      molecular mechanism whereby ethanol inhibits hepatocyte DNA synthesis is through
      its action on the IRS-1-mediated signal transduction cascade.

PMID- 7510108
TI  - The myotonin-protein kinase phosphorylates tyrosine residues in normal human
      skeletal muscle.
AB  - As a first approach to study the cellular events involved in myotonic dystrophy,
      we have produced a polyclonal antibody against a peptide sequence of the
      predicted gene product. This antibody specifically recognizes a 54 kDa protein in
      human skeletal muscle. This protein phosphorylates a co-polymer Glu/Tyr but not
      Myelin Basic Protein. This indicates that the myotonin-protein kinase has a
      tyrosine kinase activity in human skeletal muscle. This is the first
      demonstration of the kinase activity of the myotonin-protein kinase.

PMID- 7510109
TI  - Substance P receptors are differentially affected in Parkinson's and Alzheimer's
      disease.
AB  - We have quantified by receptor autoradiography the number of NK1 receptors, using
      [125I] Bolton-Hunter labeled substance P, in striatum and pallidum (internal
      (GPi) or external (GPe) segment) of patients suffering from Alzheimer's (AD) and
      Parkinson's disease (PD). When compared to non-neurologic controls, a significant
      increase in the number of NK1 sites has been observed in the striatum of PD
      patients. No significant differences were observed for the GPi and GPe. We
      observed no significant differences from controls in the number of NK1 sites in
      the striatum and pallidum of AD cases. However, the number of NK1 sites in the
      striatum of AD patients was significantly lower than that of PD patients. These
      results show that the expression of NK1 receptors in the basal ganglia is
      affected in PD.

PMID- 7510111
TI  - Gonadotropin and prolactin secretion in prepubertal female rats treated with 8
      hydroxy-2-(di-n-propylamino) tetralin.
AB  - The effect of serotoninergic activation on gonadotropin and prolactin release
      were analysed in 16-day-old intact female rats. In the first experiment, females
      were decapitated 30 min after i.p. administration of 100 mg/kg of 5
      hydroxytryptophan (5-HTP) or vehicle; in the second experiment the rats were
      decapitated 15 and 30 min after i.p. injection of vehicle or some doses (0.1, 1
      and 10 mg/kg) of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective
      agonist of the serotonin (5-HT)1A receptors. We found that: 1) serum follicle
      stimulating hormone (FSH), luteinizing-hormone (LH) and prolactin concentrations
      increased after 5-HTP administration; 2) serum LH and prolactin concentrations
      and pituitary prolactin content increased after administration of 8-OH-DPAT. Our
      results indicate that in prepubertal rats, activation of serotoninergic system
      stimulated gonadotropin and prolactin release, and that 5-HT1A receptors are
      involved in this effect. In addition, the simultaneous increase in serum and
      pituitary prolactin content suggests that 8-OH-DPAT enhances prolactin synthesis.

PMID- 7510110
TI  - Cytokines in the pathogenesis and treatment of infectious diseases.

PMID- 7510112
TI  - Reduction of nonselective adsorption of proteins by hydrophilization of
      microfiltration membranes by radiation-induced grafting.
AB  - Alcoholic hydroxyl groups were introduced into a polyethylene microfiltration
      (MF) membrane by radiation-induced graft polymerization of 2-hydroxyethyl
      methacrylate (HEMA), vinyl acetate (VAc), and glycidyl methacrylate (GMA).
      Subsequently, the VAc- and GMA-grafted membranes were quantitatively hydrolyzed
      into monool (single hydroxyl) and diol groups, respectively. The pure water flux
      of the modified membrane and the saturation capacity of bovine gamma-globulin
      onto the membrane were determined as a function of alcoholic hydroxyl group
      density. The threshold value for hydrophilization ranged between 5 and 7 mol of
      alcoholic hydroxyl group per kilogram of original MF membrane. Masking of the
      polyethylene surface with grafted polymer branches containing the diol groups was
      effective because approximately 70% of the pure water flux of the original MF
      membrane was maintained. Irrespective of the pore diameter of the original MF
      membrane, saturation capacities on the modified membrane correlated well with the
      diol group density. Saturation capacities of bovine gamma-globulin and bovine
      serum albumin were reduced to 1 mg/m2 of the membrane. In addition, the binding
      interaction changed from irreversible to reversible.

PMID- 7510113
TI  - A heat-shock-like response with cytoskeletal disruption occurs following
      hydrostatic pressure in MG-63 osteosarcoma cells.
AB  - Human osteosarcoma cells, MG-63, were exposed to a hydrostatic pressure shock of
      4.0 MPa for 20 min. Changes in subcellular distribution of the cytoskeletal
      elements and heat shock protein 70 (hsp70) were followed by indirect
      immunofluorescence and by avidin-biotin-peroxidase protocols. During recovery,
      total cellular RNA was determined and actin and aldolase mRNA content was
      followed using reverse transcription-polymerase chain reaction techniques.
      Hydrostatic pressure caused cell rounding (but not cell death), disruption of
      microtubules, collapse of intermediate filaments to a perinuclear location,
      collapse of actin stress fibers into globular aggregates in the cytoplasm, and
      the formation of several large elongated intranuclear actin inclusions. During
      recovery, the cells flattened, reorganized microtubules, and redistributed
      intermediate filaments prior to the reappearance of actin stress fibers. At 20
      and 60 min following the initiation of hydrostatic pressure, there was increased
      anti-hsp 70 staining at the nuclear membrane and concentration of hsp70 in four
      to six granules in the nucleus. At 120 min following the hydrostatic pressure,
      hsp70 showed intense staining in the cytoplasm and hsp70-containing granules in
      the nucleus disappeared. Cellular RNA decreased during the first 120-min
      posthydrostatic pressure shock and then recovered to near prehydrostatic pressure
      treatment levels by 240 min. Actin mRNA abundance, in relation to aldolase mRNA
      abundance, showed the same temporal pattern of initial decrease, followed by
      increase as did total RNA. Review of the literature indicated that eukaryotic
      cells respond to heat shock and to hydrostatic pressure by disruption of the
      cytoskeletal elements and by similar modifications in genetic expression. In this
      study, the observed responses of MG-63 cells to a 4-MPa hydrostatic pressure
      shock was like the reported response of mammalian cells to a 43 degrees C heat
      shock.

PMID- 7510114
TI  - Osteosarcoma with multiple skeletal metastases. A case of "nonstochastic"
      metastasis.
AB  - Osteosarcoma of the thoracic spine developed in a 15-year-old Japanese boy. After
      his first admission with paralysis, multiple skeletal metastases were
      demonstrated in the absence of pulmonary metastasis. This rare condition may
      possibly be considered as a unicentric osteosarcoma with bone metastases, since
      there were no precursor lesions or history of exposure to radioactive materials
      or chemical agents. These multiple lesions may be an example of so-called "organ
      specific metastasis," although this "nonstochastic" process is rare.

PMID- 7510115
TI  - Establishment of new ovarian and colon carcinoma cell lines: differentiation is
      only possible by cytokeratin analysis.
AB  - Two human ovarian (OV-MZ-10, OV-MZ-15) and two colon cancer cell lines (CO-MZ-5,
      CO-MZ-6) were newly established in permanent cell culture. These cell lines have
      been maintained in vitro for 5-6 years, the passage number varying from 25 to
      228. They were established from ascites or solid tumours at the time of primary
      surgery. By clinical and histopathological judgement alone all four cell lines
      would have been interpreted as ovarian cancer cell lines. Morphological criteria
      or the expression of the tumour-associated antigens CA-125 and CEA allowed no
      differential diagnosis. Only the analysis of the expression of different
      cytokeratins and vimentin enabled us to verify the different origin of the cell
      lines. Ovarian cancer cell lines, in contrast to the colon cancer cell lines, are
      positive for the expression of cytokeratin (CK) 7 and for vimentin. CK 20 proved
      to be the marker with the best discrimination. CK 20 was found exclusively in the
      colon carcinoma cell lines, but not in the ovarian carcinoma cell lines. The
      evaluation of cytokeratin expression is a helpful diagnostic modality in
      differentiating between adenocarcinoma cell lines derived from ovarian and colon
      tumours.

PMID- 7510116
TI  - The prognostic value of preoperative serum levels of CA 19-9 and CEA in patients
      with pancreatic cancer.
AB  - The prognostic value of preoperative serum levels of CA 19-9 and CEA was
      evaluated in 160 patients with pancreatic cancer. The survival of patients whose
      tumour marker value was below a certain cut-off level was compared with the
      survival of those with a higher value using the log-rank test. The lowest cut-off
      level dividing patients into groups with significant difference in survival (P <
      0.05) was determined by graphical analysis of chi-square values at different cut
      off levels. If stage of disease was not taken into account, there was a
      significant difference in survival between patients with low vs high preoperative
      CA 19-9 and CEA levels. When patients were classified according to stage, a
      difference was found for CA 19-9 in stage II-III patients. Patients with
      preoperative CA 19-9 below 370 U ml-1 had a significantly better prognosis than
      those with a higher level (P < 0.05). In stage I and stage IV patients, no
      significant difference was found between the groups at any cut-off level. The
      analysis of CEA showed a significant difference in survival only in stage IV
      patients, with CEA above 15 ng ml-1 being associated with shorter survival. In
      conclusion, in patients with stage II-III disease, particularly in patients with
      a non-resectable tumour, in whom the exact spread of the disease may be difficult
      to evaluate even at operation, the preoperative CA 19-9 level seems to have a
      prognostic value.

PMID- 7510117
TI  - Evaluation of a new tumour marker in patients with non-small-cell lung cancer:
      Cyfra 21.1.
AB  - The Cyfra 21.1 assay is a newly developed test which measures in serum a fragment
      of cytokeratin 19. We evaluated this marker in 212 patients with non-small-cell
      lung cancer (NSCLC), predominantly stage 3a-b and 4, and compared it with three
      other markers: carcinoembryonic antigen (CEA), squamous cell carcinoma antigen
      (SCC) and tissue polypeptide antigen (TPA). Sensitivities for Cyfra 21.1, TPA,
      CEA and SCC (using cut-off levels corresponding to a 95% specificity for benign
      lung diseases) were 40%, 40%, 42% and 19% respectively. The sensitivity of CEA
      was significantly higher in patients with adenocarcinomas compared with the other
      three markers, while the sensitivity of Cyfra 21.1 and TPA was significantly
      higher in patients with squamous cell carcinomas. The value of Cyfra 21.1 for
      monitoring disease during chemotherapy could be evaluated in 23 patients with
      squamous cell carcinomas. When the cases of lead time were included a concordance
      between clinical evaluations according to WHO response criteria and evaluations
      according to changes in the marker levels of 74% was found. The criteria defined
      for marker response were a 65% decrease in the marker level for a partial
      response and a 40% increase for progressive disease. In particular, increasing
      levels of this marker indicated usually disease progression. In conclusion, Cyfra
      21.1 is a useful serum marker for patients with NSCLC, especially for disease
      monitoring of patients with squamous cell carcinoma during and after
      chemotherapy.

PMID- 7510118
TI  - Prognostic significance of histopathological subtypes in stage I pure yolk sac
      tumour of the ovary.
AB  - The correlation between histological subtype [endodermal sinus (ES),
      polyvesicular vitelline (PV), glandular (G) and hepatoid (H) subtypes] and the
      prognosis of pure yolk sac tumours (YSTs) of the ovary was investigated. From
      1964 to 1989, 35 patients with YSTs were treated with primary surgery and
      adjuvant chemotherapy. The prevalence of histological subtypes was as follows: 14
      patients had a single subtype, either ES (12) or G (2); 12 patients had two
      subtypes, ES+G (4), ES+PV (3), ES+H (4) or G+H (1); six patients had three
      subtypes, ES+P+H (4) or ES+G+H (2); and three patients had all four subtypes.
      Multivariate analysis showed that important predictors were FIGO stage,
      chemotherapeutic regimen and residual tumour size. However, for stage I,
      multivariate analysis showed that the histological subtype was a superior
      predictor to the subclassification of FIGO stage I, age or chemotherapeutic
      regimen (P = 0.03). Kaplan-Meier analysis showed that YSTs composed of an
      admixture of three or four subtypes was associated with a better prognosis than
      those composed of one or two subtypes (P < 0.01), other variables being constant.

PMID- 7510119
TI  - Flow cytometric analysis of S-phase fraction in breast carcinomas using gating on
      cells containing cytokeratin. South East Sweden Breast Cancer Group.
AB  - We investigated distant recurrence and S-phase fraction (SPF), estimated by flow
      cytometry with and without selection of the epithelial cell population, in 201
      stage II breast carcinomas. The tumour tissue was disintegrated mechanically by
      scissors and one part of the cell suspension was treated with a detergent-trypsin
      method for single-parameter analysis, and the other part, for immunological
      selection of epithelial cells, was incubated with a monoclonal antibody (CAM 5.2)
      recognising cytokeratins 8 and 18 and a secondary fluorescein isothiocyanate
      labelled antibody. DNA was stained with propidium iodide. In order to compare the
      methods, statistical analysis was performed on the 152 tumours with S-phase
      fraction estimated by both methods. Sixty-five tumours were diploid, 81 were
      aneuploid and six tumours had different ploidy determined by the two methods.
      Using univariate regression analysis, SPF of the epithelial cell population
      predicted recurrence more effectively than SPF from single-parameter analysis. In
      multivariate regression analysis, SPF of the cytokeratin-containing population
      added significant prognostic information to the SPF of the non-selected cells. We
      concluded that the use of flow cytometric selection of epithelial breast
      carcinoma cells enhances the predictability value of SPF.

PMID- 7510121
TI  - Cantharidin-induced acantholysis: adhesion molecules, proteases, and related
      proteins.
AB  - Acantholysis is a feature of disorders such as Hailey-Hailey disease and Darier's
      disease. Immunocytochemical studies have shown internalization of desmosomal
      components after acantholysis. Basal cytokeratins show suprabasal expression in
      lesional Darier's disease. The exact mechanisms of acantholysis are still
      unclear. Cantharidin induces blistering, with suprabasal keratinocyte
      acantholysis, possibly by protease activation. Plasmin has been implicated in the
      pathogenesis of acantholysis in Darier's disease and Hailey-Hailey disease. We
      examined the distribution of desmosomal components, proteases and cytokeratins in
      cantharidin blisters, to compare them with those previously found in Darier's
      disease and Hailey-Hailey disease. Two drops of cantharidin collodion were
      applied to the skin of five normal volunteers. A 4-mm punch biopsy of the blister
      was taken, and snap frozen. Sections were stained with antibodies to desmosomal
      proteins (dp) 1/2, dp 3, desmosomal glycoproteins (dg) 1, 2/3, extracellular
      carbohydrate residues, using the lectins peanut agglutinin (PNA) and soybean
      agglutinin (SBA), proteases and cytokeratins. Acantholytic cells were stained
      diffusely with dp1/2; there was markedly reduced or absent peripheral staining
      for dp3, dg1, dg2/3, PNA and SBA. There was no clumping of stain. Plasminogen,
      fibrinogen and urokinase were expressed in some acantholytic cells. Basal keratin
      markers were expressed suprabasally in acantholytic cells. These results are
      similar to those previously obtained in Darier's disease, but different from the
      staining obtained in Hailey-Hailey disease. Extracellular glycosylated portions
      of adhesion molecules may be lost after acantholysis, perhaps as a result of
      conformational changes, internalization of extracellular domains, or proteolysis.
      The changes in the expression of plasminogen, fibrinogen, urokinase and
      cytokeratins in acantholytic cells in cantharidin-induced blisters are, as in
      Darier's disease and Hailey-Hailey disease, probably secondary to acantholysis,
      and changes in the shape of cells. We conclude that cantharidin blisters may be a
      useful model for the study of acantholysis in Darier's disease.

PMID- 7510122
TI  - Response of the clinically uninvolved skin of psoriatic patients to repeated tape
      stripping during cyclosporin A treatment.
AB  - It is well established that cyclosporin A (CyA), a widely used immunosuppressant
      in human organ transplantation, is an effective drug in the treatment of
      psoriasis. Although it has been postulated that the effect of CyA in psoriasis is
      mediated through antilymphocyte activity, there is also evidence suggesting that
      CyA exerts a direct cytostatic effect on epidermal keratinocytes, but results of
      studies relating to the latter have been contradictory. Using immunohistochemical
      methods we investigated the influence of systemic CyA on proliferation and
      differentiation in the tape-stripped uninvolved skin of psoriatic patients, a
      model which provides the opportunity of studying epidermal regeneration in the
      absence of a significant accumulation of T lymphocytes. We addressed the question
      of whether CyA (3-5 mg/kg/day) modulates epidermal proliferation and
      differentiation following standardized injury in uninvolved skin of psoriatic
      patients. Ten patients with severe psoriasis participated in this study. The
      dosages of CyA were sufficient to induce a marked and statistically significant
      improvement (PASI, week 0, 20.5 +/- 4.4; PASI, week 16, 4.3 +/- 0.6). Before CyA
      treatment, and during week 16 of treatment, Sellotape stripping was carried out
      on a 2-cm2 area of the uninvolved skin of psoriatic patients. After 48 h punch
      biopsies were taken. Immunohistochemical assessment of recruitment of cycling
      cells (Ki-67), filaggrin, involucrin, T lymphocytes and tenascin, was carried
      out. We did not find any significant alteration during the treatment period in
      the tape-stripped uninvolved skin of psoriatic patients. We conclude that
      epidermal hyperproliferation and abnormal keratinization are not modulated
      directly by CyA at therapeutic doses in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510120
TI  - Tumour cell detection in the bone marrow of breast cancer patients at primary
      therapy: results of a 3-year median follow-up.
AB  - We examined bone marrow aspirates from 100 metastasis-free primary breast cancer
      patients. In 38/100 patients (38%), tumour cells were detected in the marrow
      using an immunocytochemical technique with a cocktail of two monoclonal
      antibodies: anti-EMA and anti-cytokeratin. Median follow-up was 34 months: 15/38
      (39%) tumour cell-positive patients have since relapsed, but only 9/62 (15%)
      tumour cell-negative patients. The median interval between tumour cell detection
      and relapse was 11.4 months. No statistically significant correlation existed
      between tumour cell presence and 'established' prognostic factors. However,
      relapse-free survival was significantly shorter in tumour cell-positive patients.
      Multivariate analysis showed tumour cell presence as a strong, significant
      prognostic factor for relapse-free as well as overall survival. We conclude that
      screening for tumour cells in bone marrow of primary breast cancer patients
      identifies high-risk patients for early relapse. In particular, patients with
      node-negative tumours who have tumour cells in their bone marrow may require
      subsequent systemic therapy.

PMID- 7510123
TI  - Cutaneous T-cell lymphoma with massive co-infiltration of polyclonal B cells.
AB  - A 76-year-old man presented with a 3-month history of a cutaneous nodule on the
      right thigh. The tumour was composed of CD3+, large atypical cells, and CD20+,
      small normal-appearing cells. Flow cytometry showed that CD20+ cells outnumbered
      CD3+ cells. By Southern blot hybridization analyses, the malignant cells were
      shown to be of T-cell origin, because of the presence of rearranged bands for the
      beta chain of the T-cell receptor, but not for the immunoglobulin heavy chain.
      This case represents a T-cell lymphoma intermingled with a large number of non
      neoplastic B cells.

PMID- 7510124
TI  - Juvenile dermatomyositis: treatment with intravenous gammaglobulin.
AB  - High-dose intravenous gammaglobulin (IVGG) has proved to be effective in the
      treatment of a number of immune disorders. We report two patients with juvenile
      dermatomyositis (DM) who improved with IVGG therapy. These patients had become
      refractory to corticosteroids and had developed unacceptable steroid toxicity. We
      suggest that IVGG can be useful in the treatment of juvenile DM, by reducing
      steroid requirements, and replacing immunosuppressive drugs.

PMID- 7510125
TI  - Insulin-like growth factor binding protein 1 expression inhibits insulin-like
      growth factor I action in MCF-7 breast cancer cells.
AB  - Interactions between insulin-like growth factor I (IGF-I) and the type of I IGF
      receptor may be affected by high-affinity extracellular binding proteins. To
      date, six distinct IGF binding proteins (IGFBPs) have been identified, but their
      physiological roles are not well understood. For example, depending on
      experimental conditions, IGFBP-1 has been shown to both enhance and inhibit IGF-I
      mediated mitogenesis. We have previously shown that excess exogenous IGFBP-1
      inhibited IGF-I mediated growth of MCF-7 cells. In this study, we examined
      whether or not endogenously expressed IGFBP-1 could interfere with IGF-I mediated
      growth of MCF-7 cells. Cells were stably transfected with an IGFBP-1 expression
      vector. IGFBP-1 mRNA was produced by the cells, and protein was detected in the
      conditioned media by ligand blot and immunoblot. Type I IGF receptor could not be
      phosphorylated by IGF-I in cells expressing IGFBP-1; however, an IGF-I analogue
      (Arg-3-IGF-I), which cannot complex with IGFBPs, stimulated receptor
      phosphorylation. IGF-I did not stimulate cell growth in IGFBP-1 expressing cells.
      These results suggest that IGFBP-1 expression in MCF-7 breast cancer cells
      inhibits IGF-I induced growth by interrupting the interaction between IGF-I and
      its receptor.

PMID- 7510126
TI  - Previewing and the therapeutic use of metaphor.
AB  - This paper proposes a new technique for diagnosing and treating conflict in adult
      patients. Referred to as previewing, the technique is grounded in the
      developmental progression from somatic modes of representation to symbolic modes
      of representation. During early life, infants experience the world primarily
      through sensory phenomena. Later in childhood, however, symbolic modes of
      representation become pre-eminent. The manner in which an individual represents
      conflict reflects this developmental progression. For example, if the patient
      manifests a psychosomatic symptom, it is likely that the conflict has been
      represented on a physical level and thus emerges in somatic form; if the conflict
      is expressed as a metaphor, however, it has probably been represented on a
      cognitive level and thus emerges as a symbol. Previewing, a technique derived
      from early life interaction between mother and infant, incorporates both the
      somatic and symbolic components of psychological disorganization and may
      therefore be of benefit in psychotherapy.

PMID- 7510127
TI  - Effects of candidate autocrine and paracrine mediators on growth responses in
      isolated rat arteries.
AB  - We evaluated the effects of mediators that can be produced by smooth muscle and
      endothelial cells on growth responses in isolated arteries. Segments of carotid
      and renal arteries, denuded of endothelium, were isolated from adult rats and
      studied during tissue culture in the presence of indomethacin. Three days of
      culture in the presence of serum stimulated DNA synthesis in the media. During
      long-term culture new layers of cells developed at the borders of the arterial
      segments. Medial DNA synthesis depended less on serum than extramedial cell
      proliferation. During moderate stimulation, basic fibroblast growth factor and
      endothelin-1 enhanced and interleukin-1 and transforming growth factor-beta
      reduced medial DNA synthesis, whereas insulin-like growth factor-1, platelet
      derived growth factor AA, platelet-derived growth factor BB, and angiotensin II
      were without effect. Of these factors, only endothelin-1 stimulated extramedial
      cell proliferation. In addition, serum-stimulated but not basic fibroblast growth
      factor-stimulated medial DNA synthesis was less marked in arteries that had not
      been denuded of endothelium than in ee-endothelialized arteries. Differences
      between preparations with and without endothelium persisted in the absence of L
      arginine and in the presence of an inhibitor of nitric oxide synthase. These
      observations confirmed that DNA synthesis in the arterial media and extramedial
      cell proliferation are influenced by different factors. They further indicated
      that endothelial modulation of medial DNA synthesis does not seem to involved
      endothelium-derived prostaglandins, nitric oxide, or interleukin-1 and that it
      can be blunted by basic fibroblast growth factor.

PMID- 7510128
TI  - Enhanced intracellular stability and efficacy of PEG modified dextranase in the
      treatment of a model storage disorder.
AB  - A model for storage disorders was produced in the livers of mice by the
      administration of liposomally encapsulated FITC-dextran. Liposomally delivered
      dextranase was found to be more efficient in degrading the accumulated substrate
      as compared to the free enzyme. Dextranase was covalently modified with PEG, and
      liposomes were used as carriers for delivering the free and the modified enzyme
      to the liver at similar rates. The PEG-dextranase conjugate showed greater
      intracellular stability as compared to the native enzyme. Liposomally delivered
      PEG-dextranase, by virtue of its enhanced intracellular stability, could not only
      degrade the accumulated FITC-dextran, but could also prevent its further
      accumulation over a period of time. This enhanced intracellular stability of
      enzymes would be of importance in extending the catalytic life of therapeutically
      active enzymes and thereby improve their therapeutic potential for the treatment
      of intracellular storage disorders.

PMID- 7510130
TI  - Identification of human urinary metabolites of isbufylline by high-performance
      liquid chromatography/thermospray mass spectrometry.
AB  - Analysis of urinary metabolites of isbufylline (1,3-dimethyl-7-(2
      methylpropyl)xanthine) in healthy male volunteers after oral administration of a
      single dose of 320 mg was undertaken by high-performance liquid
      chromatography/mass spectrometry (HPLC/MS with thermospray ionization. Filtered
      urines were directed injected into the HPLC/MS system, equipped with a
      Lichrospher 100 RP 18 analytical column. The mobile phase was 0.1 M, pH 3.7
      ammonium acetate in water and acetonitrile; the composition was varied linearly
      from 5% to 40% of the organic modifier in 40 min with a flow rate of 1 ml min-1.
      Three more chromatographic peaks appeared in urines from treated subjects as
      compared to untreated ones; their probable quasi-molecular ions were at m/z 253,
      239 and 267 respectively, while the original drug, of 236 Da, was not present in
      appreciable quantity. The collisionally activated daughter ion spectra of the
      above ions allowed identification of 1,3-dimethyl-7-(3-hydroxy-2
      methylpropyl)xanthine (D3OHMPX), 1-methyl-7-(2-hydroxy-2-methylpropyl)xanthine
      (M2OHMPX), and 1,3-dimethyl-(2-carboxypropyl)xanthine (D2CMPX), the first one
      being present as glucuronic acid conjugate.

PMID- 7510131
TI  - Protein-protein interactions in reverse micelles: trypsin shows superactivity
      towards a protein substrate alpha-chymotrypsinogen A in reverse micelles of
      sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane.
AB  - Protein-protein interactions in reverse micelles of sodium bis(2
      ethylhexyl)sulfosuccinate (AOT), in isooctane containing varying amounts of Tris
      buffer are studied by using activation of alpha-chymotrypsinogen A by trypsin (EC
      3.4.21.4) to alpha-chymotrypsin (EC 3.4.21.1) as a model reaction. It has been
      found that protein-protein interactions are strongly dependent on the water
      content of the medium. At an optimum water content the activation reaction in
      reverse micelles is faster than reaction in water by a factor of 21.3. At lower
      water content both reaction rates and the conversion of alpha-chymotrypsinogen A
      into alpha-chymotrypsin decrease with decrease in water content of the reaction
      medium.

PMID- 7510132
TI  - Human granulocyte colony-stimulating factor (G-CSF), the premier granulopoietin:
      biology, clinical utility, and receptor structure and function.
AB  - In summary, both G-CSF and GM-CSF have been identified, cloned, and produced for
      pharmacologic use in humans. While both G-CSF and GM-CSF have had significant
      impact in the treatment of neutropenic states, G-CSF appears to be more
      advantageous than GM-CSF in overall efficacy and paucity of side effects. Much
      has been discovered about the structure of the G-CSF receptor but further work is
      necessary to determine its mechanism of signal transduction. As our understanding
      of G-CSF signaling advances, the therapeutic impact of our knowledge about G-CSF
      biology will evolve from the current focus on enhancing its effects in
      hematologic and oncologic illnesses to decreasing its effects in inflammatory
      conditions where overexhuberant neutrophil infiltration and activation cause
      disease.

PMID- 7510129
TI  - The effect of inhibitors of free radical generating-enzymes on low-density
      lipoprotein oxidation by macrophages.
AB  - Oxidised low-density lipoprotein (LDL) produced by the action of arterial cells,
      including macrophages, has been implicated in atherosclerosis. We have
      investigated the effect of inhibitors of various cellular free-radical generating
      enzymes on macrophage-mediated LDL oxidation. Xanthine oxidase and nitric oxide
      synthase are not responsible for LDL modification by resident mouse peritoneal
      macrophages. Eicosatetraynoic acid, a lipoxygenase inhibitor, produced a dose
      dependent irreversible inhibition of macrophage modification of LDL, but at
      concentrations rather close to those toxic to the cells. Diphenyl and diphenylene
      iodonium, NADPH oxidase and mitochondrial electron transport inhibitors,
      inhibited macrophage oxidation of LDL, at concentrations that were not obviously
      toxic. This suggests that NADPH oxidase, or some other flavin nucleotide
      dependent process, may be involved in LDL oxidation by macrophages. Wortmannin
      and thiopropionic acid dilauryl ester did not inhibit LDL oxidation, suggesting
      that inhibition of NADPH oxidase may not be the means by which the iodonium
      compounds inhibit LDL oxidation. Macrophages from C3H/HeJ mice, which lack
      receptors for lipopolysaccharide, modified LDL normally, suggesting that the
      inadvertent priming of resident macrophages by traces of lipopolysaccharide bound
      to LDL was not involved in LDL oxidation.

PMID- 7510133
TI  - Primary liver cancer incidence-rates related to hepatitis-C virus infection: a
      correlational study in Osaka, Japan.
AB  - Osaka, Japan, has one of the highest, primary liver cancer (PLC) incidence-rates
      in the world, although hepatitis-B virus (HBV) is not endemic. This paper
      addresses the question of whether the PLC-incidence variation within Osaka
      Prefecture is due to differences in the prevalence of hepatitis-C virus (HCV)
      infection. The screening data of antibody to HCV (anti-HCV) and of hepatitis-B
      virus antigen (HBsAg) in 111,069 male blood-donors, and the incidence data of
      male PLC obtained from the Osaka Cancer Registry were examined. In a multiple
      weighted regression analysis, the age-standardized incidence rate of PLC in the
      61 counties within Osaka was correlated significantly with the age-standardized
      prevalence of anti-HCV with adjustment for that of HBsAg (regression coefficient
      [RC] = 7.26, P < 0.0001). This finding was consistent with the relationship
      between the PLC incidence rate and the prevalence of high-titer (> or = 2(12))
      anti-HCV (RC = 11.18, P < 0.0001). There was significant association between the
      prevalence of HBsAg and the PLC incidence rate with adjustment for that of anti
      HCV (RC = 7.08, P = 0.018). These findings suggest that the PLC-incidence
      variation within Osaka is correlated with the geographic pattern of HCV infection
      as well as that of HBV infection among the residents.

PMID- 7510134
TI  - Alcohol consumption, smoking, and other risk factors and prostate cancer in a
      large health plan cohort in California (United States).
AB  - Alcohol consumption and cigarette smoking have been suggested as possible causes
      of prostate cancer. We therefore examined this relation in a cohort of 43,432 men
      who were members of a prepaid health plan in northern California (United States)
      and who had received a health examination in the period from 1979 through 1985.
      Detailed information on demographic variables, alcohol consumption, smoking
      habits, medical complaints and conditions, occupation, and surgery (including
      vasectomy) was assessed. Symptoms of prostatism and a history of sexually
      transmitted diseases were abstracted from the medical records of all prostate
      cancer patients and of a matched subsample of randomly selected control-subjects.
      Alcohol consumption was associated with no elevated prostate cancer risk for the
      238 men in our study in whom prostate cancer developed, but smoking one or more
      packs of cigarettes per day was associated with an adjusted relative risk (RR) of
      1.9 (95 percent confidence interval [CI] = 1.2-3.1). Prostate cancer risk for
      Black men was 2.2 (CI = 1.6-3.1) when compared with that for White men, and
      education level was associated positively in an increasing trend (P < 0.020) up
      to an RR of 1.4 (CI = 0.9-2.1) among men with postgraduate education. Symptoms of
      prostate hypertrophy were not associated with elevated risk of prostate cancer if
      they occurred two or more years before the diagnosis. The finding that smoking
      increased the risk of prostate cancer confirms the observations of others but
      needs cautious interpretation because we were unable to adjust for the potential
      confounding effect of dietary and hormonal factors.

PMID- 7510135
TI  - Nucleotide sequence and expression of a ripening and water stress-related cDNA
      from tomato with homology to the MIP class of membrane channel proteins.
AB  - The nucleotide sequence and derived amino acid sequence were determined for a
      full-length version of the tomato cDNA clone, pTOM75, the mRNA for which has
      previously been shown to accumulate in roots, ripening fruit and senescing
      leaves. Computer analysis of the predicted protein product, which we have named
      tomato ripening-associated membrane protein (TRAMP) indicates strong homology to
      known transmembrane channel proteins from other organisms. Northern analysis
      showed that this gene was induced by waterstress and that this induction was
      unaffected in an ABA-deficient genetic background.

PMID- 7510136
TI  - Isolation and characterization of a rice cDNA similar to the S-phase-specific
      cyc07 gene.
AB  - We isolated a rice cDNA clone (T151) which encodes an open reading frame of 262
      amino acids. This clone is similar to the S-phase-specific cyc07 gene of
      Catharanthus roseus. Expression of this gene is much higher in callus than in
      seedlings and regulated by external stresses such as high osmotic pressure,
      salinity, low temperature and submergence.

PMID- 7510137
TI  - Helper T cells: delivery of cell contact and lymphokine-dependent signals to B
      cells.
AB  - In the effector phase of delivering T cell help for B cell differentiation,
      proteins induced following helper T cell activation deliver cell contact signals
      to the B cell that drive its activation and proliferation. Activation induced
      soluble lymphokines also deliver signals that, in conjunction with the contact
      signals, drive B cell differentiation and immunoglobulin class switching. Helper
      T cell activation leads to transient expression of a ligand for the
      constitutively expressed B cell surface protein, CD40. The CD40 ligand is
      involved in delivering the T cell induced contact signals. Regulation of
      synthesis of the CD40 ligand by activated helper T cells contributes to the
      maintenance of specificity of the antibody response. Knowledge of the molecules
      involved in delivering T cell help allows a clearer understanding of events
      regulating antibody affinity maturation, selection and class switching in vivo.

PMID- 7510138
TI  - CD40L: a multi-functional ligand.
AB  - B cells can be stimulated to proliferate and differentiate in response to cell
      contact dependent signals provided by activated, but not resting, T cells. In the
      human system, antibodies specific for the surface antigen CD40 induce similar B
      cell responses. The cloning of a ligand for CD40, and the generation of reagents
      which can block the interaction of this ligand with its receptor, have
      demonstrated that the major component of the contact-dependent signal leading to
      B cell activation is CD40 ligand. Studies of individuals lacking functional CD40
      ligand have indicated that signaling through CD40 is essential for immunoglobulin
      (Ig) heavy chain switching and the production of all isotypes other than IgM. In
      addition to its activities on B cells, CD40 ligand is stimulatory for cells of
      monocyte and T lineages suggesting a pleiotropic role for CD40 ligand in vivo.

PMID- 7510139
TI  - The role of T/B cell interactions and cytokines in the regulation of human IgE
      synthesis.
AB  - Induction of immunoglobulin (Ig) isotype switching and isotype production by
      human B cells requires contact-mediated signals delivered by T helper cells in
      combination with cytokines. Effective T cell help requires T cell activation
      resulting in a rapid expression of T cell membrane proteins, which interact with
      ligands constitutively expressed on B cells. These interactions lead to B cell
      activation, proliferation and, in the presence of cytokines, to isotype switching
      and immunoglobulin synthesis. The nature of the T cell antigens involved in these
      T/B cell interactions, and their role in human B cell activation resulting in IgE
      synthesis in the presence of IL-4 and IL-13, will be discussed.

PMID- 7510140
TI  - [The histochemical demonstration of biogenic monoamines in normally developing
      amphibian embryos and in exposure to a permanent magnetic field].
AB  - It was shown that the permanent magnetic fields at 35-40 mT1 inhibit the activity
      of biogenic monoamines in developing amphibian embryos. The effect was
      quantitatively similar to that of PMF at 40 mT1 (3-hour exposure during 6 days).
      The most significant fluctuations in their activity were observed at the stages
      of blastoderm formation and gastrulation onset.

PMID- 7510141
TI  - Stimulation of granulopoiesis by high-dose recombinant human granulocyte colony
      stimulating factor in children with aplastic anemia and very severe neutropenia.
AB  - We investigated the efficacy and safety of high-dose recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) in treating 10 children with
      severe aplastic anemia and fewer than 0.05 x 10(9)/L neutrophils. Doses of rhG
      CSF ranging from 400 to 2,000 micrograms/m2/d were administered as a 30-minute
      intravenous infusion daily for 4 weeks. In 6 of the 10 children, treatment
      increased the neutrophil count by 10-fold to greater than 60-fold (range, 0.21 to
      1.8 x 10(9)/L). Bacterial or fungal infections that were present at study entry
      resolved in all 6 responders, who are still alive with a median survival of more
      than 27 months (range, 15 to 54 months) since the initiation of treatment. Three
      of 4 nonresponders died of infection, whereas 1 nonresponder received a bone
      marrow transplant and is alive. No serious toxicity was attributable to rhG-CSF.
      It was well tolerated at doses up to 2,000 micrograms/m2/d and effectively
      stimulated granulopoiesis. This agent thus offers promise as adjuvant treatment
      for severe infections in children with aplastic anemia and very severe
      neutropenia.

PMID- 7510142
TI  - Granulocyte colony-stimulating factor (G-CSF) production and G-CSF receptor
      structure in patients with congenital neutropenia.
AB  - Congenital neutropenia (Kostmann's syndrome [KS]) is an autosomal recessive
      syndrome that is characterized by profound neutropenia, resulting in major
      clinical infections and death. Since the neutropenia and symptoms in KS improve
      in response to exogenous administration of granulocyte colony-stimulating factor
      (G-CSF), we studied bone marrow cytokine (G-CSF, granulocyte-macrophage CSF [GM
      CSF], and interleukin-6) production under both basal and stimulated conditions.
      No differences in G-CSF, GM-CSF, or IL-6 gene expression were found in bone
      marrow stromal cells between normal controls and KS patients, and all three
      cytokines were detected by enzyme-linked immunosorbent assay (ELISA) in medium
      conditioned by bone marrow stromal cells from normal donors and patients with KS.
      Each KS patient tested had detectable, functional G-CSF in their own serum before
      exogenous G-CSF administration. Since G-CSF production appeared normal in KS
      patients, we then asked whether we could detect structural defects in the
      signaling portion of G-CSF receptor genes. Polymerase chain reaction (PCR)
      amplification of the G-CSF receptor transmembrane region alone, and of the
      transmembrane plus cytosolic portions of the receptor, yielded the size products
      predicted from the sequences of the normal G-CSF receptor. Single-strand
      conformational polymorphism (SSCP) analysis of G-CSF receptor PCR products
      demonstrated no variance in structural conformation between KS patients and
      normal subjects. These results demonstrate that bone marrow stromal cells in
      patients with KS secrete normal concentrations of functional G-CSF and suggest
      that the neutropenia in KS patients is caused by an inability of neutrophilic
      progenitor and precursor cells to respond to normal, physiologic levels of G-CSF.
      Such a defect, clinically responsive to pharmacologic doses of G-CSF, might be
      caused by defects in the post-G-CSF receptor signal transduction pathway.

PMID- 7510143
TI  - Effects of interleukin-3 and c-kit ligand on the survival of various classes of
      human hematopoietic progenitor cells.
AB  - We examined the effects of interleukin-3 (IL-3) and c-kit ligand (KL) on the
      survival of differentiated hematopoietic progenitor cells (HPC), the burst
      forming unit-erythroid (BFU-E); colony-forming unit-granulocyte, erythroid,
      monocyte, megakaryocyte (CFU-GEMM); and CFU-granulocyte-monocyte (CFU-GM) and
      more primitive hematopoietic cells that give rise to these progenitor cells (pre
      colony-forming cells [pre-CFC]). CD34+ HLA-DR+ cells, which are highly enriched
      for committed HPC, and CD34+ HLA-DR- c-kit+ cells, which contain the most
      primitive assayable hematopoietic cells, including long-term bone marrow culture
      initiating cells, high proliferative potential-CFC, the CFU-blast, and the BFU
      megakaryocyte, were suspended in serum-free medium in the presence or absence of
      IL-3 or KL. CD34+ HLA-DR+ cells incubated under serum-free conditions or in the
      presence of KL for 96 hours lost greater than 90% of assayable unilineage or
      multilineage HPC, whereas those cells incubated in the presence of IL-3 retained
      40% of the number of HPC present at time 0. The effect of IL-3 on HPC survival
      was most pronounced on the BFU-E and CFU-GEMM present within CD34+ HLA-DR+ cells.
      Addition of IL-3, but not of KL, to CD34+ HLA-DR+ cells delayed the appearance of
      morphologic changes and DNA fragmentation patterns associated with cell death
      occurring by apoptosis. CD34+ HLA-DR-c-kit+ cells were incubated under similar
      serum-free conditions in the presence or absence of IL-3 or KL, and the frequency
      of pre-CFC was determined by limiting dilution analysis. The frequency of pre-CFC
      in cells incubated for 48 hours in the absence of serum was similar to that of
      cells incubated in the presence of IL-3 and approximately doubled when CD34+ HLA
      DR- c-kit+ cells were incubated in the presence of KL. Addition of KL to serum
      free suspension cultures of CD34+ HLA-DR- c-kit+ cells delayed the appearance of
      DNA fragmentation patterns associated with apoptosis to a greater extent than did
      the addition of IL-3. These studies suggests that IL-3, but not KL, promotes HPC
      survival, whereas KL plays a greater role than IL-3 in sustaining more primitive
      HPC, such as pre-CFC. The effects of both cytokines in mediating HPC and
      primitive hematopoietic cell survival appear to be related, in part, to their
      ability to suppress apoptosis.

PMID- 7510144
TI  - Lymphoid and myeloid differentiation of single human CD34+, HLA-DR+, CD38-
      hematopoietic stem cells.
AB  - Multilineage differentiation of human fetal bone marrow CD34+ cell subsets was
      examined using a single-cell liquid culture assay. Four CD34+ cell populations,
      ie, (1) CD38-, HLA-DR+, (2) CD38-, HLA-DR-, (3) CD38+, HLA-DR-, and (4) CD38+,
      HLA-DR+ cells, were sorted as single cells into 96-well flat-bottom culture
      plates containing long-term culture medium supplemented with interleukin-3,
      interleukin-6, stem cell factor (SCF), granulocyte-macrophage colony-stimulating
      factor, erythropoietin, basic fibroblast growth factor (bFGF), and insulin-like
      growth factor-1 (IGF-1). Single CD34+, CD38-, HLA-DR+ cells had the highest
      replating efficiency as well as the highest replating efficiency. The cellular
      composition of the single-cell progeny was studied by morphologic and/or flow
      cytometric examination. Only the progeny of single CD34+ cells that lacked CD38
      could give rise to each of the hematopoietic cell lineages. The expansion of the
      progeny of single CD34+, CD38-, HLA-DR+ cells was examined in more detail and
      showed three clearly distinguishable growth patterns: 28% (SD, +/- 10%; n = 14)
      of the single cells formed cell clusters/colonies; 9% (SD, +/- 4%; n = 14) formed
      dispersed cells; and 11% (SD, +/- 6%; n = 14) gave rise to a mixture of cell
      clusters and dispersed cells. The dispersed cell growth pattern was reduced when
      SCF or bFGF and IGF-1 was absent in the growth factor cocktail. The replating
      ability of the dispersed cells was considerably larger than that of cells with
      other growth patterns, in that 76% of the cells that gave rise to dispersed cells
      and 54% of the cells that gave rise to dispersed cells as well as cell clusters
      gave rise to a second generation, but only 7% of the cells that gave rise to cell
      clusters gave rise to a second generation. The second generation of cells
      continued to produce third and fourth generations after repetitive replating,
      except for the replated cells from cell clusters. In contrast with the first
      generation progeny, SCF did not have an influence on the replating ability of the
      cells. Only in the progeny of single CD34+, CD38-, HLA-DR+ cells that gave rise
      to dispersed cells was each of the hematopoietic cell lineages found, ie, B
      lymphocytes, neutrophils, monocytes, macrophages, osteoclasts, basophils/mast
      cells, eosinophils, erythrocytes, megakaryocytes, and platelets.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7510145
TI  - Plasma P-selectin is increased in thrombotic consumptive platelet disorders.
AB  - P-selectin is a 140-kD protein found in the alpha-granules of platelets and the
      Weibel-Palade bodies of endothelial cells that on cell activation is expressed on
      the cell surface and also secreted into the plasma. The secreted form of P
      selectin, like plasma P-selectin, differed from platelet membrane P-selectin in
      that its molecular mass was approximately 3 kD lower under reducing conditions.
      Both the secreted and plasma forms of P-selectin contained cytoplasmic sequence
      as determined by Western blot analysis with an affinity-purified rabbit anti-P
      selectin cytoplasmic peptide antibody. We have measured plasma P-selectin and
      beta-thromboglobulin (beta TG) concurrently in (1) patients with consumptive
      thrombotic disorders, including disseminated intravascular coagulation (DIC),
      heparin-induced thrombocytopenia (HIT), and thrombotic thrombocytopenic purpura
      (TTP)/haemolytic uremic syndrome (HUS); (2) patients with idiopathic
      thrombocytopenic purpura (ITP); and (3) healthy controls. Patients with DIC, HIT,
      and TTP/HUS, but not ITP, had significantly elevated plasma P-selectin and beta
      TG levels when compared with their age-matched healthy controls. The increased
      plasma P-selectin and beta TG in patients with thrombotic disorders were likely
      to be the result of in vivo platelet and endothelial cell damage or activation.
      We also found that avoidance of veno-occlusion and other tedious measures
      customarily taken during blood collection and sample preparation to prevent in
      vitro platelet activation did not affect plasma P-selectin assay results. In
      addition, plasma P-selectin levels were not influenced by the presence of renal
      failure or heparin administration. These results indicate that plasma P-selectin
      may be a useful new marker for thrombotic diseases.

PMID- 7510146
TI  - Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by
      anti-CD19 monoclonal antibody.
AB  - Antigenic modulation is one of many factors determining the effectiveness of
      monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb
      most suitable for radioimmunotherapy of patients with B-cell malignancies, we
      studied the influence of MoAb isotype on modulation, after binding of the MoAb to
      different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of
      CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch
      variant. We provide evidence that this difference in modulation rate is caused by
      the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments
      aimed at elucidating the mechanism of Fc gamma RII involvement in modulation
      induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19
      MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb
      resulted in enhanced calcium mobilization in Daudi cells. This increased signal
      induction accompanies the enhanced capping and subsequent modulation of CD19
      antigens. Because Fc gamma RII is expressed in varying densities on malignant B
      cells in all differentiation stages, our results have implications for the MoAb
      isotype most suitable for use in MoAb-based therapy of patients with B-cell
      malignancies.

PMID- 7510147
TI  - Rapid detection of deletions causing delta beta thalassemia and hereditary
      persistence of fetal hemoglobin by enzymatic amplification.
AB  - A considerable number of deletions of variable size and position that involve the
      beta-globin gene complex on chromosome 11 are associated with the clinical
      entities of hereditary persistence of fetal hemoglobin (HPFH) and delta beta
      thalassemia. Specific deletions appear to be associated with consistent
      phenotypes and some are known to be recurrent. To facilitate the molecular
      diagnosis of uncharacterized patients with HPFH and delta beta thalassemia,
      oligonucleotide primers have been designed to enzymatically amplify deletion
      specific products for nine known deletions, which include those responsible for
      HPFH-1, HPFH-2, HPFH-3, Spanish (delta beta)zero thalassemia, hemoglobin (Hb)
      Lepore, Sicilian (delta beta)zero thalassemia, Chinese G gamma(A gamma delta
      beta)zero thalassemia, Asian-Indian inversion-deletion G gamma(A gamma delta
      beta)zero thalassemia, and Turkish inversion-deletion (delta beta)zero
      thalassemia. Using this approach, we have successfully characterized the
      molecular basis for delta beta thalassemia in 23 individuals from 16 families of
      diverse ethnic origins. Thirteen individuals from this group were shown to be
      heterozygous for the 13.4-kb Sicilian deletion, two were heterozygous for the 100
      kb Chinese G gamma(A gamma delta beta)zero deletion, four were heterozygous for
      the Turkish form of inversion-deletion delta beta thalassemia, and three were
      heterozygous for the Asian-Indian form of inversion-deletion G gamma(A gamma
      delta beta)zero thalassemia. One Vietnamese subject was heterozygous for a 12.6
      kb deletion, which we have fully characterized at the molecular level. Sequence
      analysis of the breakpoint regions of the Chinese deletion and the Turkish
      rearrangement indicates that, in each case, the mutation is likely to have arisen
      from a single origin. This hypothesis is supported by the evident geographical
      clustering of the various deletions described here.

PMID- 7510149
TI  - Cytokeratins patterns in childhood primary liver tumors.
AB  - Expression of cytokeratins no. 7 and no. 19, typical of the mature biliary tract
      and of embryonic and fetal hepatocytes, has been evaluated in primary liver
      tumors from 12 children. Of 7 children with hepatoblastoma, 6 were strongly
      reactive for cytokeratin no. 19 and only 4 were weakly positive for cytokeratin
      no. 7. In contrast, the remaining tumors, including 2 hepatocarcinomas, 1
      sarcoma, 1 hamartoma and 1 hemangioma were positive for cytokeratin no. 7, while
      cytokeratin 19 was present in 1 hepatocarcinoma and in the hamartoma. All these
      tumors, as well as 1 hepatoblastoma and the sarcoma, were also reactive for
      cytokeratin no. 8, typical of hepatic cells.

PMID- 7510148
TI  - Immunogenicity of fusion proteins. An example of tumor-specific/transformation
      related antigens.
AB  - Fusion proteins are generated in some solid tumors and hematological neoplasias
      by inter- or intrachromosome translocations. These proteins are believed to play
      a causal role in the pathogenesis of these diseases. Fusion proteins, therefore,
      can be considered tumor-specific/transformation-related molecules. The targeting
      of such structures could lead in the future to significant progress in the
      therapeutic index of anti-cancer treatment, by allowing the selective destruction
      of neoplastic cells. In this article, the author reviews the different oncogenic
      fusion molecules so far known, the mechanism(s) by which they are generated and
      the available information regarding their immunogenicity, and analyzes their
      potential use as future targets for a specific immune response.

PMID- 7510150
TI  - Effects of prostaglandin of E, F and I series, leukotriene C and platelet
      activating factor on amylase release from isolated rat pancreatic acini.
AB  - Exogenous eicosanoids were reported to affect pancreatic secretion, but it is
      unknown whether this effects is mediated by the changes in pancreatic circulation
      or by direct action on pancreatic secretory cells. In this study the effects of
      prostaglandins (PG), leukotriene C4 (LTC4) and platelet activating factor (PAF)
      and the blockers of their biosynthesis or receptor antagonists on amylase release
      from the isolated rat pancreatic acini were examined. The acini were incubated
      with pancreatic secretagogues, such as caerulein or urecholine in the presence or
      absence of various concentrations (10(-9)-10(-5) M) of PGE2, Nocloprost (stable
      analog of PGE2), PGI2, PGF1 alpha, LTC4, PAF, indomethacin (inhibitor of
      endogenous PG formation) and A-63162 (blocker of endogenous LT biosynthesis).
      PGE2, PGI2 and PGF1 alpha inhibited secretagogues-stimulated enzyme secretion
      from isolated pancreatic acini but their inhibitory potency was about 1000 times
      lower, on molar basis, than that of Nocloprost. PAF and LTC4 produced
      concentration-dependent stimulation of amylase release from the unstimulated
      acini reaching about 50% of caerulein-induced maximal response and enhanced
      amylase release induced by caerulein or urecholine. The effects of PAF and LTC4
      were reversed by the addition of respective receptor antagonist for PAF (TCV-309)
      and for LTC4 (FPL-55712). These results indicate that PG inhibit, while PAF and
      LTC4 stimulate pancreatic enzyme secretion and thus could be implicated in the
      control of this secretion.

PMID- 7510151
TI  - Significance of granulocyte colony-stimulating factor (G-CSF)-induced increases
      in LDH.

PMID- 7510152
TI  - Effects of negative charges of a model for bovine pancreatic trypsin inhibitor
      folding intermediate on the peptide folding.
AB  - A peptide model (called P alpha P beta) of bovine pancreatic trypsin inhibitor
      (BPTI) for studying the peptide folding structure was designed as a crucial
      folding intermediate. The P alpha P beta model folded but it was unstable at low
      pH. Four acidic groups in P alpha P beta: Glu-49, Asp-50, and C-termini at Phe-33
      and Ala-58, were replaced individually with an Ala (in case of Glu and Asp) and
      an amide group (for C-terminal carboxyl groups) to study the effects of these
      negative charged groups on folding structure in terms of thermal stability and pH
      dependence. Substituting the Glu-49 or Asp-50 with Ala and blocking the C
      terminus carboxyl group of Phe-33 in P beta destabilized the structure, but
      blocking the negative charge of C-terminus in Ala-58 of P alpha stabilized the
      structure at neutral pH. These results can be interpreted in terms of helix
      dipole momentum effects and/or salt bridge formation between Asp-50 and Arg-53,
      and of electrostatic interaction between positive and negative charges, which
      stabilized the structure. The melting temperature of model peptides (Tm) in low
      ionic strength buffer were lower than that in high ionic strength buffer except
      the C-terminus blocking of P alpha.

PMID- 7510153
TI  - Lethal and sub-lethal toxicity of lindane to Pimephales promelas and Ceriodaphnia
      dubia.

PMID- 7510154
TI  - [Immunohistologic, ultrastructural and morphometric characterization of organ
      cultures of the human limbus epithelium].
AB  - Transplantations of limbus epithelium play a steadily increasing role in the
      therapy of chemical burns, recurrent erosions, and impaired differentiation of
      the limbus epithelium (LE). To assess the vitality of LE under different culture
      conditions, LE was excised from 30 patients and cultivated in media with serum
      (F12 + 10% FCS) and without it (S4 and F12). AE5 antigen (64K keratin) was
      expressed by the LE specimens in these 3 media with an intensity similar to that
      of uncultivated specimens. All specimens strongly expressed EGF and PDGF-beta
      receptors under serum-free culture conditions, while serum-containing cultures
      reduced the expression of these receptors. Among the cells which migrated from
      the conjunctival preparations into the culture medium, connective tissue cells
      (anti-vimentin), macrophages (mac 1 and mac 2 antibodies), epithelial cells (AE5
      antibody) and cells expressing class II antigen (Tu 39 and Tu 22 antibody) were
      determined. Only in the S4 medium were neither macrophages nor class II antigen
      positive cells found. The epithelial thickness was unchanged before and after
      incubation with S4 medium. The two other media caused a reduction in thickness of
      the epithelium. The average size of the epithelial cells increased non
      significantly in all cultures. Ultrastructurally, the organ cultures incubated in
      S4 medium showed practically no degenerative cell changes. On the basis of the
      criteria used here for quality checks of LE organ cultures, S4 appears to be the
      medium best suited on the basis of functional (PDGF-beta and EGF receptors) and
      morphological criteria (keratin expression, epithelial thickness and epithelial
      cell size).

PMID- 7510157
TI  - [Diseases of the visceral organs as a result of brain damage].
AB  - In the late period even following mild closed brain injury, diseases of the
      viscera and the body's systems develop as a result of diffuse lesions in the
      brain regions. Experimental studies have shown that this is associated with
      impaired self-regulatory mechanisms responsible for energy metabolic processes in
      the brain.

PMID- 7510155
TI  - Renal proximal and distal tubular function is attenuated in diabetes mellitus
      type 1 as determined by the renal excretion of alpha 1-microglobulin and Tamm
      Horsfall protein.
AB  - Diabetic nephropathy is usually characterized by glomerular dysfunction; the view
      that tubular damage occurs as a consequence, however, has been disputed. To
      verify this hypothesis we compared glomerular with proximal and distal tubular
      parameters in 62 patients with diabetes mellitus type I. The duration of disease
      ranged between 0 and 39 years and the glomerular, proximal tubular, and distal
      tubular parameters were investigated in 24-h urine samples. Excretion of albumin
      as a marker of the glomerulum, alpha 1-microglobulin and N-acetyl-beta-D
      glucosaminidase as parameters of proximal tubule, and Tamm-Horsfall protein as
      parameter of distal tubule were determined by sensitive enzyme-linked
      immunosorbent assays. Patients were divided into five groups (D1-D5) according to
      the duration of diabetes as follows: D1, less than 1 year; D2, 1-4 years; D3, 5-9
      years; D4, 10-14 years; D5, longer than 14 years. Healthy individuals (n = 61)
      aged 3-42 years served as controls. Significantly increased excretion of proximal
      tubular parameters were found in early course while albumin excretion was still
      in the normal range. In addition, proximal tubular alpha 1-microglobulin showed
      an increase during the course of diabetes duration, probably indicating an early
      proximal tubular impairment. Distal tubular Tamm-Horsfall protein showed
      increasing excretion in D1-D4, which may reflect disturbance of the thick
      ascending loop of Henle. Our results therefore stress the importance of tubular
      parameters such as alpha 1-microglobulin during early diabetes mellitus type I
      since they may serve as early markers of renal dysfunction and may precede
      albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510156
TI  - [Simplified vibriocidal antibody titer performed on a drop of blood].
AB  - We report a simplified technique for vibriocidal antibody test in underprivileged
      people in tropical area. The test is performed on a drop of blood sampled on a
      disc of blotting paper. It avoid taking of large quantities of blood in timid
      underfed people who are often solicited. Its reading is rapid and easy by the
      naked eye owing to staining viable germs violet by the neotetrazolium succinate.
      Tested in mice and humans, the simplified method gave data well correlated to
      those obtained with the standard test on serum for vibriocidal titres higher than
      (or equal to) 1/40.

PMID- 7510158
TI  - [The neurology of terminal states].
AB  - The paper gives a theoretical justification of CNS abnormality developing in
      patients who have a history of critical and terminal states, including clinical
      death. The most significant abnormality is that which is termed posthypoxic
      and/or postresuscitation encephalopathies whose nature has not been elucidated
      particularly at the cellular and molecular levels. It is emphasized that this
      involves brain abnormalities, which is a sequela of hypoxia or ischemia of
      systemic origin, rather than primary brain damages. In some patients who have
      sustained a severe hypoxic episode of any nature and recovered their
      psychoneurological status ever rapidly and rather fully, there may be an abrupt
      progressive deterioration of their neurological status in some days or months,
      which results in death or grave irreversible disability. It is concluded that not
      only do reparative and compensatory processes occur, but also there are phenomena
      of progressive degenerative changes in a primarily successfully resuscitated
      person or experimental animal in the central nervous system in the
      postresuscitation period. A classification of psychoneurological disorders in
      patients in the early postresuscitation period has been made and ways of their
      prevention or alleviation have been indicated.

PMID- 7510160
TI  - [Psychoneurologic aspects of infections caused by the human immunodeficiency
      virus].
AB  - The clinical and follow-up analysis of 213 cases (including 144 males and 69
      females) with human immunodeficiency virus-induced infection at different stages
      and 14 autopsies characterizes the factors which have a negative influence on the
      CNS. These include opportunistic infections, concomitant infections, chronic
      alcoholism, drug abuse, premorbid altered background, endogenous diseases,
      psychosexual disorientation concerning the sex of the object, psychogenic
      reactions. It is concluded that there are difficulties of distinguishing the
      symptomatology directly associated with human immunodeficiency virus
      neurotropism. There are positive and negative trends in the lifestyle of the HIV
      infected persons and AIDS patients.

PMID- 7510159
TI  - [Perinatal hypoxic CNS lesions in neonates].
AB  - The paper reviews the causes of perinatal brain lesions, shows the involvement of
      disturbances of cellular membrane structural and functional properties and blood
      brain barrier permeability in the pathogenesis of hypoxic CNS lesions for
      neurospecific proteins. It also provides evidence for the principles of
      management of pregnancy, labor and early neonatality at a risk for cerebral
      abnormalities to reduce childhood disability.

PMID- 7510161
TI  - [Neurohumoral induction of structural and functional compensatory reorganization
      of the damaged brain].
AB  - A correlation has been found between the time course of the biological activity
      of specific oligo- and polypeptide factors in cerebrospinal fluid and the
      effectiveness of motor function recovery. The fluid as a donor material
      accelerates the compensatory process in recipient animals with unilateral
      neocortical damage. The procedure stimulates the formation process of connections
      of the centrally denervated semisegments of the spinal cord with the
      somatosensory cortex of the intact brain hemisphere. Endolumbar introduction of
      cerebrospinal fluid from reconvalescents induced the regress of symptoms of
      central motor disorders in patients with stroke sequelae.

PMID- 7510162
TI  - [Biochemical asymmetry of the brain: myth or reality?].
AB  - Unilateral brain damage results in the appearance of oligopeptide factor of
      complete asymmetry (CAF) producing a lateralized effect on spinal centers during
      intracisternal administration. The action vector of CAF is determined by the side
      of brain damage. The right- and left-sided CAF differ in chemical structure.
      Their CAFs are species-unspecific. The findings suggest that there is a chemical
      labeling of the right and left brain in the mammals (including man). From this
      point of view, fundamental and medical aspects of biochemical brain asymmetry are
      analyzed.

PMID- 7510163
TI  - [Mechanisms of changes in functional hemispheric relations].

PMID- 7510164
TI  - [Multilevel neurochemical organization of the brain].
AB  - Many years' studies in functional neurochemistry have provided a concept of the
      functionally induced biochemical heterogeneity of neurons and their subcellular
      components, which is formed during ontogenesis as the functions of the central
      nervous system are developed. It has been established that it manifests itself at
      the systemic, cellular, and subcellular levels: (1) between brain formations
      which constitute the single functional system; (2) between the neurons of various
      morphofunctional types (associative, efferent, afferent ones) between the neurons
      and the glia; (3) between individual components (the nucleus and the cytoplasm)
      of a neuron and its subcellular (synaptosomes, mitochondria, synaptosomal
      membranes) components. It is concluded that the functionally determined
      biochemical heterogeneity and morphofunctional features found in animals of
      various strains may be regarded as one of the ways of compensatory,
      rehabilitative, and adaptative processes in the central nervous system.

PMID- 7510165
TI  - [The problem of the individual variability of the human brain].
AB  - Series of frontal sections, 20 microns thick, were used to study the individual
      cytoglio-architectonic features of fields 8.8, 39, 40, 41, 43, 44, 45, 47 of the
      caudate nucleus, dorsomedial nucleus of the thalamus, Meynert's nucleus in 12
      persons aged 29 to 89 years. The profile fields of neurons, their density and the
      density of gliocytes, including perineuronal ones were measured by computed
      morphometry, the cellular composition was determined from size of neurons, as
      well as the neuroglial and neuroperineuronal indices were defined. In 6 cases
      (distinguished, gifted persons), all the formations under study showed structural
      signs (abundant satellitosis, predominant large neurons, etc.) suggesting that
      there is a high functioning of nerve cells whose quantitative parameters are
      greater than those in other cases.

PMID- 7510166
TI  - [Specifics of the formation of the alpha rhythm in different areas of the
      cerebral cortex in young children].
AB  - The age-specific features of distribution of capacity density values of modally
      specific monoherz components of optic alpha-rhythm and their response
      rearrangements to light stimulus suggest that in 2-3-year-old children, alpha
      rhythm appears as three monoherz segments in the range 6-9 Hz with their
      heterodirectional changes. At this age stage of brain functional maturation, the
      authors have identified the border of synchronous and spasmodic changes in the
      spectral coherent indices of bioelectric activity formation in the projection and
      associative regions of the brain, which corresponds to 14-15 months of life.

PMID- 7510167
TI  - [The energy aspect of the brain activity in normal aging and in Alzheimer's
      disease].
AB  - In normal aging and Alzheimer's disease, there are regular changes in brain
      energy homeostasis, which are associated both with the time course of the average
      level of catabolism and with the intensity rate of catabolic processes by
      hemispheres. In normal aging, there is generally decrease in the catabolic level
      estimated by the level of the DC potential. In Alzheimer's disease, the level of
      catabolism secondarily increases. The findings suggest that there is a causal
      relationship between the brain energetic homeostasis and the visual information
      processes. The correlation of energetic and information processes increases with
      normal and especially pathological aging. The authors' methods enabled them to
      observe the time course of energy metabolism and to reveal their critical levels.
      The correction of energetic processes in due time should be useful in preventing
      atrophic changes in the brain with aging.

PMID- 7510168
TI  - [Present problems of neuroimmunology].
AB  - The paper provides the data available in the literature and their own findings of
      immunopathological impairments in the central nervous system, and spinal cord and
      polyneuropathies. The most detailed comparison of immunological and
      clinicotomographic changes is made in system lupus erythematosus. With this, a
      correlation is shown between peripheral vascular diseases (butterfly,
      capillarites, reticular livedo, Raynaud's syndrome), the levels of circulating
      immune complexes and local neurological abnormality. Particular attention is paid
      to the antiphospholipid syndrome. A relationship is found in patients with
      neurolupus and Sneddon's syndrome between cardiolipin antibodies and various
      (mainly vascular and ischemic) neurological syndromes as recurrent cerebral
      circulatory disturbances, episyndromes, etc.

PMID- 7510169
TI  - [The pharmacologic analysis of modulated substance P induced by stimulation of
      the lateral hypothalamus].
AB  - The present investigation was undertaken to examine the neurochemical mechanisms
      of the modulatory effect of substance P (SP) on feeding behavior induced by
      threshold electrical stimulation of the lateral hypothalamus (LH) in rabbits. The
      administration of SP, 15 nmol, was found to transform feeding induced by
      stimulation of LH into escape. The phenomenon was shown to begin at min 20, and
      to last up to min 60 after SP injection. In the experiments, some antagonists of
      classic neurotransmitters were injected into the marginal vein of the rabbit ear.
      An important role of catecholaminergic and M-cholinergic formations in the brain
      in the SP transformation of their feeding behavior into escape was found in
      electric stimulation of LH. H-cholinergic and GABA-ergic antagonists produced no
      effect on the modulatory effect of SP.

PMID- 7510170
TI  - [Forgetfulness and amnesia: receptor mechanisms and brain mapping].
AB  - Inability to remember and amnesia have been shown to be active neurochemical
      processes. The coupled processes (blockade of the triggering DA stimulating
      system and activation of the inhibitory GABA-ergic system with the predominant
      value of postsynaptic D-2 receptors) are a neurochemical basis for development of
      amnesia. The mechanisms of spontaneous forgetting is provided by a decrease in
      the activity of the dopaminergic system along with the enhancement of
      benzodiazepine-GABA-ergic interferentional inhibition. The observed changes in
      dopamine metabolism, para-tyramine appearance, as well as restructure of D-2
      receptors provide the activity of dopamine increasing mechanism which determines
      the retention of memory traces. A computer model of the spatial interaction of
      the dopamine membrane-receptor complex was constructed by scanning the samples of
      synaptic membranes after learning and amnesia. A new method of inducing
      psychogenic amnesia in human beings has been elaborated. Amnesia is characterized
      by the absence of increases in the number of cortical connections reflecting the
      emotional factor of information.

PMID- 7510171
TI  - [Dopaminergic mechanisms of the oculomotor behavior of primates].
AB  - Behavioral changes and eye movements were studied through chronic low-dose MPTP
      exposure (ten intramuscular injections of 0.2 mg/kg per day) in four monkeys
      (Macaca rhesus). The monkeys developed the deficit of spontaneous saccades and
      decreased oculomotor range. The vertical component of saccades were hardly
      reduced. The examination of vestibuloocular reflex revealed no changes (r =
      approximately 1.0), but the fast phase of nystagmus was blocked.

PMID- 7510172
TI  - [The concept of a common medical information space: a new technology of
      integrated data for the improvement of health].
AB  - The concept of the common medical information space proposes that there are
      available health data kept in the data bases of various automatic medical
      systems. This data integration is achieved by integrating computers into the
      network, which will make a regular exchange of data among the functionally
      related medical institutions. The above concept of the common medical
      informational space is a basis for organizing a comprehensive monitoring for the
      health status of children (including the ecomedical aspect) at the basically new
      technological level, creating conditions for practical implementation of the
      concept of the continuum of the developing body's states, which will take into
      account the influence of many interacting factors on the developing fetus and
      child.

PMID- 7510173
TI  - [The role of viruses in neuropathology: old and new problems].

PMID- 7510174
TI  - [Current approaches to the treatment of severe influenza].
AB  - The complex pathogenetic therapy of severe (complicated) forms of influenza
      infection is proposed. The drugs with antioxidant, antiprotease or
      immunomodulating activities are used for the purpose. The clinical character of
      infection or stage of pathologic process are considered for appropriate drug
      application. The advantages of drugs with diversified mechanisms of action
      involved in the complex treatment of influenza are demonstrated.

PMID- 7510175
TI  - [Role of interleukin-2 receptor in mitogenic action of C-reactive protein on
      lymphocytes].
AB  - There is evidence that native pentameric C-reactive protein (CRP) and its
      nonmitogenic monomeric subunits compete with IL 2 at the level of lymphocyte
      proliferation triggering and block IL 2 receptors due to structural and antigenic
      similarities between CRP and IL 2. The mechanisms of mitogenic action of CRP and
      evolutionary bases of the CRP-cytokine system relationship are discussed.

PMID- 7510176
TI  - ["Forbidden" lymphocytes clones].
AB  - The investigations of humoral autoimmune phenomena in healthy subjects have found
      autoantibodies to different structure self-antigens in the sera of all examinees.
      It is concluded that autoantibody-producing lymphocytes are a normal
      morphological component of the immune system which is frequently present in man
      and mammals.

PMID- 7510177
TI  - [New information on the histopathology of Vilyui encephalomyelitis: possible role
      of copper deficiency].
AB  - The nature of a pathological process in the central nervous system in Vilyui
      encephalomyelitis defines it as a specific entity of demyelinative
      encephalomyelitis with a drastic prevalence of an alternative component. The bulk
      of the nerve parenchyma dies from circulatory incompetence due to blood vascular
      diseases, which are typical of the disease, as a peculiar angiopathy and
      progressive reduction in the microcirculatory bed. Homeostatic disorders in the
      myelinic membranes of central nervous fibers were found to be of value. The
      maintenance of homeostasis is implicated by adequate oligodendroglial function
      and copper metabolism. The inhabitants of the Republic of Sakha (Yakutia) are
      demonstrated to have oligodendroglial hypoplasia and exogenous and endogenous
      copper deficiency. This is suggested by low copper amounts in the natural
      environmental objects and in the hair of patients with chronic Vilyui
      encephalomyelitis.

PMID- 7510178
TI  - [Effect of genetic structure on hereditary diseases in Russian populations].
AB  - Several characteristics of the lead of hereditary diseases can be distinguished.
      These include: the mean values of a prevalent autosomal dominant; autosomal
      recessive and X-linked recessive disorders in a population; the spatial
      distribution of families with hereditary diseases, especially those with
      autosomal recessive disorders in a population; and diverse hereditary pathologies
      in the population. All these characteristics are shown to be influenced by the
      genetic pattern of Russian populations, namely by random inbreeding which varies
      significantly in northern rural populations, but which is virtually equal to 0 in
      northern urban and southern Russian populations. The rate of migration is another
      factor of the genetic pattern which also affects the load of hereditary diseases.

PMID- 7510179
TI  - [Molecular diagnosis of genetic diseases in Russia: current status and
      perspectives].
AB  - The paper reviews the current molecular diagnosis of common socially significant
      inherited diseases such as cystic fibrosis, Duchenne muscular dystrophy,
      hemophilia A and B, phenylketonuria. It also provides basic results of prenatal
      diagnosis of these diseases and detection of their heterozygous carriage in Saint
      Petersburg, as well as brief evidence for the molecular diagnosis in other
      Russia's areas. There is a need for increasing the number of hereditary diseases,
      such as Willebrand's disease, Martin-Bell syndrome, polycystic kidney, Huntington
      chorea, myotonic dystrophy, etc. to be diagnosed at the molecular level. Evidence
      is provided for the necessity to set up specialized medical genetic centers for
      diagnosing common inherited diseases and for the expediency of their
      implementation if more rare genetic diseases are diagnosed. Some perspectives for
      the molecular diagnosis of genetic diseases are briefly outlined. The paper
      discusses the significance of the studies to solve the basic problems of the
      "Human genome" programme and the tasks of health care.

PMID- 7510180
TI  - [Theoretical approaches to the evaluation of antiviral drug effectiveness].
AB  - It is suggested that (a) LD50 is the measure of the efficacy of antiviral drugs:
      (b) a disease is characterized by the "barrier" type of a pathological process
      when in pathogenesis there exists an event whose manifestation largely determines
      the outcome of a disease (recovery/severe form with a fatal outcome). If the
      event consists in the penetration of a pathogen into a susceptible cell and the
      consequent reproduction of an antigen, the value LD50 for man is expressed as the
      same parameter for a model animal and as the parameters determined by in vitro
      human and animal cell experiments. The parameters include the degree of viral
      production adsorption on the cell and the levels of its reproduction. The
      algorithms for evaluating the efficacy of viral drugs are based on the
      relationship. The adequacy of the relationship is illustrated by experimental
      findings.

PMID- 7510181
TI  - [Administration, maintenance and expression of foreign genetic body in eukaryotic
      systems: approaches to gene therapy].

PMID- 7510182
TI  - [Labilization of DNA structure of peripheral blood leukocytes in patients with
      systemic lupus erythematosus].

PMID- 7510183
TI  - [Total ultraviolet irradiation of circulating blood].

PMID- 7510184
TI  - [Bioethics].

PMID- 7510185
TI  - [Long-term effect of petrochemical production on girls and young women during
      vocational training and work].
AB  - A complex of hygienic, clinical, statistical and experimental studies established
      the relationship, magnitude, nature, and mechanism of changes in the body of
      girls who are engaged in petrochemical industry and in contact with the
      occupational factors of current petrochemical production. The most significant
      and prognostically poor factors include disturbances in the formation and
      realization of reproductive function (a menstrual cycle, pregnancy course, labor,
      postpartum period, posterity health), which were experimentally evidenced
      (gonadotoxic, embryotropic, mutagenic, and teratogenic effects were found to be
      shown by a number of hydrocarbons in concentrations not exceeding the allowable
      ones).

PMID- 7510187
TI  - [History of surgery in the Academy of Medical Sciences].

PMID- 7510186
TI  - [Hygienic rationale for diagnosis and correction of excessive body weight in
      schoolchildren with physical training].
AB  - The results have shown that schoolchildren with moderate body mass (M +/- 0.3
      sigma) have the highest physical capacity for work (PWC 170/kg) and
      schoolchildren with body mass from M + 0.3 to M + 1 sigma show a decrease by 20%
      and with an excessive body mass M + 1.75 sigma by more, about 40%. Bearing in
      mind this rough drop of capacity to work and the significant aggravation of
      functional state with an excessive body mass M +/- 1 sigma we consider that
      limitation of body mass standard by limits M +/- 0.67 sigma is advisable. The
      studies showed the high efficiency of exercises of cyclic nature (swimming,
      running, skiing, bicycle) with a view to correcting disorders due to obesity.

PMID- 7510188
TI  - [Theoretical basis for the criteria of optimal design of antiviral drugs].

PMID- 7510189
TI  - Palliative chemotherapy for advanced non-small cell lung cancer.

PMID- 7510190
TI  - Treatment of minimal residual disease in myeloid leukemia--the immunotherapeutic
      options with emphasis on Linomide.
AB  - It is now known that syngeneic transplantation, T lymphocyte depletion and
      absence of graft-versus-host disease all increase the risk of relapse following
      allogeneic transplantation for the myeloid leukemias, both acute and chronic.
      Leukemia-specific immune responses appear to play a major role in the therapy of
      the myeloid leukemias. In recent years attempts have been made to better
      characterize and effectively utilize these antileukemic immune responses,
      concentrating on clinical states of minimal residual disease. This review will
      discuss the role of such immunotherapy following autologous bone marrow
      transplantation for myeloid leukemias, and will focus on recent experience and
      ongoing clinical trials using the novel immunomodulator Linomide.

PMID- 7510191
TI  - Levels of serum granulocyte colony-stimulating factor in patients with chronic
      myeloid leukemia.
AB  - To clarify the patho-physiologic role of granulocyte colony-stimulating factor (G
      CSF) in chronic myeloid leukemia (CML), we determined the serum levels of G-CSF
      in various stages of CML using a very sensitive method: chemiluminescence enzyme
      immunoassay (CLEIA). This method makes it possible to estimate very low levels of
      serum G-CSF. In the present study, serum samples from 25 patients in chronic
      phase and 16 in blastic crisis, as well as samples from 33 healthy volunteers
      were investigated. The serum G-CSF levels in chronic phase of CML (2.95 +/- 3.91
      pg/ml) were significantly lower than those in normal controls (15.92 +/- 6.53
      pg/ml) and in blastic crisis of CML (15.52 +/- 17.65 pg/ml) within a range of
      very low levels (p < 0.001, p < 0.02). Moreover, a reverse correlation between
      blood neutrophil counts and serum G-CSF levels were clearly demonstrated for CML
      including blastic crisis (r = 0.405, p < 0.02). Interestingly, a sequential
      parallel relation was observed between serum G-CSF levels and neutrophil alkaline
      phosphatase (NAP) scores for a patient with CML in chronic phase. Our
      observations indicate that a negative feedback mechanism exists between
      peripheral neutrophils and serum G-CSF levels in the chronic phase of CML, and
      that very low levels of G-CSF in chronic phase of CML might be an important cause
      for the low NAP scores.

PMID- 7510192
TI  - Prevention of chemotherapy-induced neutropenia using G-CSF with VACOP-B--a case
      report.
AB  - Hematopoietic growth factors, including granulocyte colony-stimulating factor (G
      CSF), are being increasingly used to prevent chemotherapy-induced neutropenia. We
      report a patient with aggressive non-Hodgkin's lymphoma who was successfully
      supported with G-CSF through a weekly VACOP-B chemotherapy regimen. The patient
      had become severely neutropenic at week 3, requiring a one-week delay. For the
      remainder of the treatment, G-CSF at a dose of 4 micrograms/kg/day was
      administered daily over 4 days after week 4, then over 3 days thereafter,
      beginning the day after the non-myelosuppressive weeks (vincristine/bleomycin). A
      total of 5 such G-CSF courses were given, with no further neutropenia despite
      administration of full chemotherapy doses on schedule. This case suggests that,
      at least with the VACOP-B regimen, chemotherapy-induced neutropenia can be
      prevented using much lower quantities of G-CSF than has been reported using other
      regimens.

PMID- 7510193
TI  - Human stem cell transplantation.

PMID- 7510195
TI  - White cell transfusions born again.

PMID- 7510194
TI  - G-CSF in the treatment of acute myeloid leukemia: is it safe?
AB  - Recent studies of granulocyte colony stimulating factor (G-CSF) in the treatment
      of myeloid leukemia in Japan have revealed that: 1) G-CSF accelerates neutrophil
      recovery significantly after intensive chemotherapy or bone marrow
      transplantation (BMT); 2) G-CSF decreases the number of febrile days and the
      incidence of documented infections; 3) daily administration of G-CSF, starting
      from two days before chemotherapy or starting from two days after the end of
      chemotherapy, tended to increase the remission rate; 4) there is no evidence of
      stimulation by G-CSF of the growth of myeloid leukemia cells if it is used for a
      short period of time and if the number of leukemic cells is highly reduced by
      chemotherapy; 5) there is no evidence that G-CSF administration increases relapse
      rates of leukemia after chemotherapy or BMT. However, until further randomized
      studies answer these questions, caution must be exercised to avoid unnecessary
      stimulation of neutrophil production, and G-CSF should not be given to myeloid
      leukemia patients with a large number of leukemic cells left.

PMID- 7510197
TI  - Hematopoietic growth factor therapy of myelodysplastic syndromes.

PMID- 7510198
TI  - CD48 monoclonal antibody K31 for bone marrow transplantation: T-depleting
      capacity and influence on hematopoietic progenitors.

PMID- 7510200
TI  - Distribution of alpha-galactosyl-containing epitopes on Trypanosoma cruzi
      trypomastigote and amastigote forms from infected Vero cells detected by Chagasic
      antibodies.
AB  - Reactivity of different Trypanosoma cruzi developmental forms with purified
      Chagasic anti-alpha-galactosyl antibodies (anti-Gal) was studied using
      epimastigotes from axenic cultures, trypomastigotes and amastigotes from infected
      Vero cell cultures, and an immunogold labeling method as observed by electron
      microscopy. Epimastigotes were poorly labeled, whereas extracellular
      trypomastigotes and amastigotes bound heterogeneously to the antibody with many
      cells being intensely labeled at the cell surface, including the membrane lining
      the cell body, the flagellum and the flagellar pocket. Parasites with poor
      labeling at the cell surface generally had several gold particles within the
      cell, mostly in cytoplasmic vacuoles. The Golgi complex of trypomastigotes was
      strongly labeled. Intracellular parasites were labeled at the parasite cell
      surface or within vacuolar structures. The expression in T. cruzi-infected Vero
      cells of alpha-galactosyl antigenic structures acquired from the parasite was
      shown by moderate labeling with Chagasic anti-Gal of the membrane lining parasite
      free outward cell projections. The reactivity with purified anti-Gal from healthy
      individuals at the same concentrations of Chagasic anti-Gal was poor, with gold
      particles appearing in the nucleus and cytoplasm but not at the cell surface. It
      paralleled the labeling with Bandeireae simplicifolia IB-4 lectin. The results
      provide a basis for autoimmune reactions involving anti-Gal from chronic Chagasic
      patients.

PMID- 7510196
TI  - Treatment of myelodysplastic syndromes with AML-type chemotherapy.

PMID- 7510199
TI  - Adoptive immunotherapy in human and canine chimeras.

PMID- 7510202
TI  - Effect of peptide nicking in the human chorionic gonadotropin beta-subunit on
      stimulation of recombinant human thyroid-stimulating hormone receptors.
AB  - It is now generally accepted that human chorionic gonadotropin (hCG) has thyroid
      stimulating activity. Heterologous forms of the hCG molecule occur in the
      purified preparations extracted from urine of pregnant women and patients with
      trophoblastic diseases. This work was undertaken to determine the effect of
      peptide nicking in the hCG-beta subunit on its thyrotropic potency. Using Chinese
      hamster ovary cells expressing functional human thyroid-stimulating hormone (TSH)
      receptors, we examined the effect of nicked hCG on cycliC AMP (cAMP) production
      and receptor binding. The effect of human leukocyte elastase (hLE), a nicking
      enzyme, on standard hCG also was examined in the cAMP assay and on receptor
      binding. We studied five hCG preparations extracted from the urine of normal
      pregnancy (CR-127 and P8) and trophoblastic diseases (C2, C5 and M4). Two
      preparations (C2, 96% nicked and M4, 100% nicked in the beta 44-49 region) showed
      about a 1.5-fold potency of standard hCG CR-127, which is also 20% nicked in the
      same region. Non-nicked hCG (P8) had the weakest potency among all of the samples
      tested. Treatment of standard hCG with hLE increased the cAMP response about two
      fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE
      increased the cAMP response about two-fold. Dose-dependent displacement of bovine
      [125I]TSH by standard hCG and hLE-digested hCG was observed and was almost
      identical. We have confirmed the increased in vitro thyrotropic activity of hCG
      nicked in the beta-intercysteine loop on recombinant human TSH
      receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510201
TI  - Increased expression of the monocyte differentiation antigen CD14 in extrinsic
      allergic alveolitis.
AB  - Expression of the CD14 antigen was studied on alveolar macrophages in extrinsic
      allergic alveolitis (EAA), using immunocytochemistry and cytometry. Compared to
      control donors, EAA patients had higher percentages of My4 positive cells (40
      versus 22%), and the antigen density was fourfold higher (410 versus 92
      channels). Levels of soluble CD14 (sCD14) in serum were found to be increased in
      EAA patients with an average of 4.6 +/- 1.5 micrograms.ml-1 compared to 3.2 +/-
      0.7 micrograms.ml-1 in controls. Follow-up of patients with antigen avoidance
      revealed a concomitant decrease of CD14 staining of alveolar macrophages (AMs)
      and of sCD14 in serum, whilst allergen exposure induces both parameters. These
      data are consistent with the concept that antigen contact upregulates CD14
      expression on AMs in EAA, followed by shedding and increase of sCD14 in serum.

PMID- 7510204
TI  - Acidic fibroblast growth factor is expressed abundantly by photoreceptors within
      the developing and mature rat retina.
AB  - In order to further understand the role(s) of fibroblast growth factors (FGFs) in
      the development, differentiation and function of the central nervous system, we
      analysed the expression of the mRNA, and the presence and tissue distribution of
      the translated product, of one member of the FGF family, acidic FGF (aFGF),
      within the mammalian retina. Firstly, the relative abundance of aFGF mRNA was
      assayed in embryonic (between 14 and 17 days of gestation), postnatal (between 1
      and 17 days after birth) and adult rat retina by quantitative reverse
      transcription-coupled polymerase chain reaction amplification using specific aFGF
      oligonucleotides. The level of expression remained uniformly low throughout the
      embryonic period and until postnatal day 7. Therefore the quantity of aFGF mRNA
      increased rapidly, reaching 80% of adult levels by eye opening (postnatal day
      13). Adult levels were three-fold higher than at early developmental times. In
      situ hybridization of adult rat retina using specific antisense aFGF riboprobes
      revealed labelling in all cellular layers. Antisera raised against recombinant
      human aFGF revealed very little labelling of 4-day postnatal retina, but by
      postnatal days 8 and 17 immunoreactive aFGF was localized mainly within the
      photoreceptor cell bodies. Western blots of retinal extracts derived from 17-day
      embryonic, 4-day postnatal and adult retina probed with the same antibody
      revealed a single immunoreactive band of the expected molecular weight (18 kDa)
      in all extracts. Thus aFGF is mostly transcribed and translated within the retina
      subsequent to the major steps of cell birth, migration and differentiation, and
      seems to be abundantly expressed by maturing photoreceptor cells.

PMID- 7510203
TI  - Distribution of secretoneurin-like immunoreactivity in comparison with substance
      P- and enkephalin-like immunoreactivities in various human forebrain regions.
AB  - The distribution of secretoneurin-like immunoreactivity, a peptide derived from
      secretogranin II, was studied by means of immunocytochemistry and compared to the
      pattern of staining for substance P- and enkephalin-like immunoreactivities in
      the human basal forebrain, with special reference to the basal ganglia.
      Secretoneurin-like immunoreactivity was characterized by gel filtration and
      reversed-phase high pressure liquid chromatography analysis. Chromatographic
      analysis revealed a single peak for secretoneurin-like immunoreactivity. No
      secretoneurin-immunopositive forms of high molecular weight were found.
      Secretoneurin-like immunoreactivity appeared mainly in dot- and fibre-like
      structures. In addition, a band-like terminal staining (woolly fibres) that has
      been shown by others for substance P- and enkephalin-like immunoreactivities, was
      also observed for secretoneurin-like immunoreactivity. Medium-sized cells were
      found arranged in clusters or singly within the caudate and putamen. In the basal
      ganglia, a high density of secretoneurin-like immunoreactivity was found in the
      internal segment of the globus pallidus, the ventral pallidum and in the pars
      reticulata of the substantia nigra. In these areas the immunostaining appeared
      mainly as woolly fibres. The bed nucleus of the stria terminalis and medial
      amygdala displayed a high density of fine beaded secretoneurin-like
      immunoreactive fibres, sometimes forming pericellular contacts. The nucelus
      basalis of Meynert was highly innervated by secretoneurin-like immunoreactive
      fibres, mainly in the form of woolly fibres. In general, a large overlap was
      found between secretoneurin- and substance P-like immunoreactivity in all
      examined areas of the basal ganglia. In the bed nucelus of the stria terminalis
      and medial amygdala secretoneurin-like immunoreactivity was distributed very
      similarly to enkephalin-like immunoreactivity. These data provide evidence that
      in different subsets of neurons and neuronal pathways secretoneurin-like
      immunoreactivity coexists with substance P- and enkephalin-like immunoreactivity
      in several areas of the human brain.

PMID- 7510205
TI  - Immediate early gene expression in the rat forebrain following striatal infusion
      of quinolinic acid.
AB  - Expression in the rat forebrain of immediate early genes belonging to the fos and
      jun families was investigated at various time points following an intrastriatal
      infusion of quinolinic acid. Fos immunoreactivity was rapidly and transiently
      induced, exhibiting maximal intensity 2 h post-lesion, and was principally
      located in neuronal nuclei situated around the periphery of the lesioned
      straitum, in regions that subsequently show little, if any, neurodegeneration.
      Fos immunoreactivity was additionally expressed throughout the ipsilateral
      cortex. In contrast, Jun immunoreactivity, which remained undetectable for 12 h
      after the lesion, reached its maximal intensity 24 h post-lesion, at which time
      it was most densely distributed in neuronal nuclei found within the central
      lesioned areas of the striatum. In situ hybridization analysis using
      radiolabelled oligonucleotide probes confirmed this spatial and temporal
      separation between c-fos and c-jun expression within the striatum and extended it
      further, showing that, whilst jun mRNA displayed very similar expression
      characteristics to those of c-fos mRNA, both fos B mRNA and jun D mRNA exhibited
      induction patterns closely resembling those of c-jun mRNA. These results clearly
      suggest that two distinct programmes of immediate early gene expression can be
      induced in vivo. The rapid (2 h) and transient induction of c-fos/jun B may well
      be a response to NMDA receptor activation, whereas the molecular signal for the
      late (24 h) and sustained induction of c-jun/fos B/jun D is currently a focus for
      our investigations.

PMID- 7510207
TI  - Free sensate secondary skin flaps: an experimental study on patterns of
      reinnervation and neovascularisation.
AB  - The main purposes of the present study were: 1) to compare differences, if any,
      in the patterns of reinnervation between secondary skin flaps, created either
      from "innervated skin grafts" or from ordinary denervated skin grafts; 2) to
      examine the influence of time, and the possible roles of granulation tissue and
      fibrosis in reinnervation following implantation of a nerve trunk into a
      secondary skin flap at different stages; and 3) to compare neovascularisation
      before and after free transfer of these flaps. Neurovascular changes were studied
      in a rat model by microangiography and by immunohistochemical techniques, using
      antisera to protein gene product 9.5 (panneural marker), to calcitonin gene
      related peptide (sensory neurones) and to von Willebrand Factor (endothelial cell
      marker). The results indicate a potential clinical role for secondary sensate
      skin flaps where conventional methods of reconstruction including free
      neurovascular flap transfers are not available.

PMID- 7510206
TI  - Localization of nitric oxide synthase in the mouse olfactory and vomeronasal
      system: a histochemical, immunological and in situ hybridization study.
AB  - The distribution of nitric oxide synthase (NOS) in the mouse olfactory bulb and
      olfactory epithelium, including the vomeronasal organ, was studied using an anti
      NOS antibody, NADPH diaphorase histochemistry and in situ hybridization with NOS
      specific antisense oligonucleotide probes. Interneurons containing NOS protein
      and mRNA, and exhibiting NADPH diaphorase activity were detected in the plexiform
      layer of the main olfactory bulb and the granule cell layer of main and accessory
      olfactory bulbs. Periglomerular cells and granule cells in the main olfactory
      bulb were also NOS positive with diaphorase and immunostaining for NOS. In
      contrast, no evidence for NOS expression was found either in the main olfactory
      epithelium or in the vomeronasal organ, in spite of the strong diaphorase
      staining of the surface of the main olfactory epithelium. Polymerase chain
      reaction amplification experiments for detection of NOS gene expression further
      indicated that NOS is expressed in the olfactory bulb but not in either the main
      olfactory epithelium or vomeronasal organ. Use of an antibody raised against
      another enzyme, NADPH-P450 oxidoreductase, showed that this protein was strongly
      expressed in the olfactory epithelium. Activity of this enzyme may account for
      the diaphorase histochemical staining of the epithelia. An involvement of
      neuronal nitric oxide synthase in signalling in olfactory receptor neurons is
      therefore doubtful, although NOS is clearly expressed in neurons in both main and
      accessory olfactory bulbs.

PMID- 7510209
TI  - Alzheimer's paired helical filaments: amyloid precursor protein epitope mapping.
AB  - Paired helical filaments (PHF) were electrophoretically purified and solubilized
      from Alzheimer's neurofibrillary tangles and consisted of a primary 66 kDa
      protein on SDS-PAGE analysis. A panel of antibodies raised against restricted
      regions of the beta-amyloid precursor protein (APP) were employed for epitope
      mapping studies of this 66 kDa PHF protein. Western blot studies revealed that C
      terminal APP antibodies were immunoreactive with the 66 kDa PHF protein. Further
      analysis revealed that only antisera raised against peptides that include the
      beta/A4-amyloid region within the C-terminal portion of APP were immunoreactive
      with PHF proteins. These data complement previous immunocytochemical studies
      which indicated that C-terminal APP antibodies preferentially label PHF
      containing neurofibrillary tangles in Alzheimer's brain. The present data suggest
      a similarity of secondary or tertiary structure between beta/A4-amyloid and PHF
      which accounts for the cross-reactivity of beta/A4-amyloid antibodies with PHF
      proteins.

PMID- 7510208
TI  - Afferent connections of the anterior thalamus in rabbits.
AB  - This study was designed to determine whether axons of cholinergic dorsal
      tegmental neurons terminate on cells in the anterior thalamus in rabbits as in
      other species, and to localize projecting tegmental cells for future studies of
      their contributions to anterior thalamic learning-relevant neuronal activity. The
      distribution of retrogradely labeled neurons was examined following injections of
      wheat germ agglutinin horseradish peroxidase (WGA-HRP) centered in the anterior
      ventral (AV) thalamic nucleus. The results confirm past findings in rabbits
      indicating projections to anterior thalamus from the mammillary nuclei, the
      posterior cingulate cortex, presubiculum and postsubiculum. Demonstrated for the
      first time in rabbits were projections from the lateral dorsal and the
      pedunculopontine tegmental nuclei, locus coeruleus, dorsal raphe nucleus,
      Gudden's dorsal tegmental nucleus, pretectum and reticular thalamic nucleus.

PMID- 7510211
TI  - The influence of environmental factors on behavioural problems in 8-year-old
      children exposed to amphetamine during fetal life.
AB  - Sixty-five children born to women who all used amphetamine during pregnancy were
      followed prospectively up to the age of 8 years. There was a statistically
      significant correlation between the extent (among and duration) of amphetamine
      exposure during fetal life and psychometric tests, aggressive behavior,
      adjustment and general assessment, indicating a worse outcome for children who
      had been more exposed to the drug. Alcohol use during pregnancy as well as
      attitude towards pregnancy also showed a statistical correlation to the outcome.
      Predictors of the child's psychosocial environment were few and only maternal
      psychiatric treatment, alcohol abuse and number of custodians correlated with
      aggressive behavior and general assessment.

PMID- 7510212
TI  - [Radioimmunodetection of prostatic cancer: in vivo 131I-gamma-seminoprotein for
      diagnosis of prostatic cancer by nuclear imaging].
AB  - 69 patients with prostatic cancer were subjected to radioimmunodetection (RAID)
      with 131I-labeled antibody against gamma-seminoprotein (gamma-Sm), the images of
      malignant tumor sites was obtained by single photon emission computed tomography
      (SPECT) with dual radionuclide and computer processing. Of the 69 patients 66
      were confirmed by RAID. The ratio of tumor tissue to normal tissue (T/N) 6.9 and
      the best time for incaging was 96 hours after injection of anti-gamma-Sm. The
      diameter of the minimum tumor in RAID was 0.5 cm. metastatic prostatic cancer in
      the pelvis or bone location as well as the origin tumors were also detected in 13
      cases. Anti-gamma-SmRAID can differentiate benign from malignant prostatic
      neoplasms. In 37 cases of benign prostate hyperplasia, only two were positive.
      The positive detective rate of B-ultrasound and CT was 70.8% and 73.1%
      respectively.

PMID- 7510213
TI  - [Effects of GABA and substance P on metabolism of striatal dopamine following
      experimental cerebral ischemia].
AB  - Using both the RIA and HPLC-EC methods, we studied the effect of intrastriatal
      injection of bicuculline (Bic), a GABA antagonist as well as the intranigral
      injection of [D-Arg1, D-phe5, D-Trp7-9, Leu11] substance P, the SP antagonist on
      the metabolism of dopamine (DA) at the striatum after the unilateral irreversible
      occlusion of the right middle cerebral artery (MCAO) of rats. Intrastriatal
      injection of 80 nmol Bic increased DOPAC level except DA and HVA in the striatum.
      The increase of striatal DOPAC was statistically significant in the MCAO group as
      compared with that in the non-ischemic controls. The above effects of
      intrastriatal Bic on DA and its metabolites were completely reversed with an
      intranigral injection of 5 nmol of substance P. It is suggested that the effect
      of intrastriatal Bic on DA metabolites in the striatum is mediated by substance P
      in the substantia nigra and that the regulatory effect of GABA and SP on striatal
      DA is working in middle cerebral artery occlusion.

PMID- 7510210
TI  - [Hemodynamics, lymphatic circulation and ultrastructure of the lungs during
      hemodilution with blood substitutes].
AB  - The effect of substitution hemodilution on transcapillary fluid exchange in the
      lung was studied in experiments on 30 dogs. After administration of Ringer's
      solution and of oncotic solutions (3.4% and 10% Rheodextran), the lymph flow
      through the right lymphatic trunk was measured and the protein content in the
      lymph was determined. The obtained results were compared with electron
      micrographs of the lung. Ringer's solution was found to escape rapidly from the
      vascular bed. A 3.9-fold increase in lymph flow was recorded and edematous
      changes were observed in the interstitial space. Administration of 10%
      Rheodextran induced an 8.3-fold increase of lymph flow and enhanced also the
      protein transport in the lymph. The permeability of pulmonary endothelial
      vascular walls was deranged. Isooncotic 3.4% Rheodextran provided adequate
      transcapillary exchange of fluids in the lungs and proved to be the suitable
      solution for substitution of blood losses. In the ultrastructure of the lungs no
      pathological changes were observed. (Fig. 8, Ref. 33).

PMID- 7510215
TI  - Metaphase chromosome structure: bands arise from a differential folding path of
      the highly AT-rich scaffold.
AB  - Using the highly AT-specific fluorochrome daunomycin, a longitudinal optical
      signal called AT queue, thought to arise from a line-up of the highly AT-rich
      scaffold-associated regions (SARs) by the scaffolding, was identified in native
      chromosomes. Fluorescence banding is proposed to result from a differential
      folding path of the AT queue during its progression from telomere to telomere.
      The AT queue is tightly coiled or folded in a Q band, the resulting transverse
      striations across the chromatid, which also represent Giemsa subbands, generating
      a bright AT-rich signal over the Q region. The R bands, in contrast, contain a
      more central (unfolded) AT queue, yielding an AT-dull signal over the R regions.
      The AT queue is identified by immunofluorescence against topoisomerase II (topo
      II) and HMG-I/Y as the scaffold of native chromosomes; the fluorescence signal
      from both proteins is akin to a detailed Q-type banding pattern. Native
      chromosomes appear assembled according to the loop-scaffold model.

PMID- 7510214
TI  - Expression of CD44 in prostate cancer cells.
AB  - Expression of CD44, the cellular hyaluronate receptor, was examined in human
      prostate cell lines. CD44 mRNA was detected in cell lines PC3 and DU145, both
      established from organ metastases of prostate adenocarcinoma, but not in cell
      line LNCaP, established from a lymph node metastasis. PC3 and DU145, but not
      LNCaP, are tumorigenic and metastatic in nude mice. Of the CD44 mRNA species
      identified, the standard CD44s as well as variant isoforms CD44v7, CD44v10,
      CD44v14, CD44v13-v14, CD44v12-v14 and CD44v7-v14 are represented.

PMID- 7510216
TI  - Interferon activation of the transcription factor Stat91 involves dimerization
      through SH2-phosphotyrosyl peptide interactions.
AB  - Stat91 (a 91 kd protein that acts as a signal transducer and activator of
      transcription) is inactive in the cytoplasm of untreated cells but is activated
      by phosphorylation on tyrosine in response to a number of polypeptide ligands,
      including interferon alpha (IFN-alpha) and IFN-gamma. We report here that the
      inactive Stat91 in the cytoplasm of untreated cells is a monomer and that upon
      IFN-gamma-induced phosphorylation it forms a stable homodimer. Only the dimer is
      capable of binding to a specific DNA sequence directing transcription. Through
      dissociation and reassociation assays, we show that dimerization of Stat91 is
      mediated through SH2-phosphotyrosyl peptide interactions. Dimerization involving
      SH2 recognition of specific phosphotyrosyl peptides may well provide a prototype
      for interactions among family members of STAT proteins to form different
      transcription complexes.

PMID- 7510219
TI  - [The curative effect of pingyangmycinum in treating pterygium].

PMID- 7510217
TI  - Copurification of E. coli RNAase E and PNPase: evidence for a specific
      association between two enzymes important in RNA processing and degradation.
AB  - Ribonuclease E (RNAase E) was isolated in a complex that also contained
      polynucleotide phosphorylase (PNPase). Besides copurification, evidence for an
      association of these enzymes comes from sedimentation and immunoprecipitation
      experiments. Highly purified RNAase E correctly processed E. coli 5S ribosomal
      RNA, bacteriophage T4 gene 32 mRNA and E. coli ompA mRNA at sites known to depend
      on the rne gene for cleavage in vivo. The difference between previous smaller
      estimates of the size of RNAase E and that reported here apparently is due to the
      sensitivity of the enzyme to proteolysis during purification. The discovery of a
      specific association between RNAase E and PNPase raises the intriguing
      possibility that these enzymes act cooperatively in the processing and
      degradation of RNA.

PMID- 7510220
TI  - Role of prostate specific antigen (PSA) and carcinoembryonic antigen (CEA) in
      screening for prostate and recurrent colon cancers in the elderly.

PMID- 7510218
TI  - Structural basis for the binding of proline-rich peptides to SH3 domains.
AB  - A common RXL motif was found in proline-rich ligands that were selected from a
      biased combinatorial peptide library on the basis of their ability to bind
      specifically to the SH3 domains from phosphatidylinositol 3-kinase (PI3K) or c
      Src. The solution structure of the PI3K SH3 domain complexed to one of these
      ligands, RKLPPRPSK (RLP1), was determined. Structure-based mutations were
      introduced into the PI3K SH3 domain and the RLP1 ligand, and the influence of
      these mutations on binding was evaluated. We conclude that SH3 domains recognize
      proline-rich motifs possessing the left-handed type II polyproline (PPII) helix
      conformation. Two proline residues directly contact the receptor. Other prolines
      in the ligands appear to function as a molecular scaffold, promoting the
      formation of the PPII helix. Three nonproline residues consisting of combinations
      of arginine and leucine interact extensively with the SH3 domain and appear to
      confer ligand specificity.

PMID- 7510221
TI  - Nitric oxide synthase inhibition with NG-mono-methyl-L-arginine reversibly
      decreases cerebral blood flow in piglets.
AB  - OBJECTIVE: We tested the hypothesis that, in piglets, the intravenous
      administration of the reversible inhibitor of nitric oxide synthase, NG-mono
      methyl-L-arginine, decreases cerebral blood flow via a mechanism unrelated to
      cerebral oxygen consumption. DESIGN: Prospective, randomized, controlled animal
      study. SETTING: Animal laboratory at a university. SUBJECTS: Pentobarbital
      anesthetized piglets (1 to 2 wks of age; 2.6 to 4.0 kg). INTERVENTIONS: Piglets
      were treated with either 50 mg of NG-mono-methyl-L-arginine, 100 mg of NG-mono
      methyl-L-arginine, or an equal volume of saline by intravenous infusion over 10
      mins. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure increased after NG
      mono-methyl-L-arginine (50 mg dose: 84 +/- 6 to 100 +/- 7 mmHg; 100 mg dose: 82
      +/- 4 to 107 +/- 4 mmHg; p < .001). Forebrain blood flow (microspheres) decreased
      (37 +/- 2 to 30 +/- 2 mL/min/100 g; p < .05) and cerebrovascular resistance
      increased (2.1 +/- 0.2 to 3.5 +/- 0.3 mmHg/mL/min/100 g; p < .05) only after 100
      mg of NG-mono-methyl-L-arginine. Neurohypophysis blood flow decreased to 56 +/-
      9% of the control value, while forebrain blood flow decreased only to 81 +/- 4%
      of the control value after 100 mg of NG-mono-methyl-L-arginine administration.
      Blood flow returned to control values by 30 mins after infusion. NG-mono-methyl-L
      arginine administration had no effect on cerebral oxygen consumption at either
      dose. Intravenous administration of L-arginine (300 mg) immediately after the
      infusion of 100 mg of NG-mono-methyl-L-arginine was associated with prompt (by 3
      mins) recovery of blood flow to all brain regions that were affected by NG-mono
      methyl-L-arginine. CONCLUSIONS: These data suggest that nitric oxide and/or a
      nitric oxide-containing substance is an important mediator of cerebrovascular
      tone in piglets, acting via a mechanism unrelated to altering cerebral oxygen
      consumption.

PMID- 7510222
TI  - Transport of fluorescent dextrans across the rat ileum after cutaneous thermal
      injury.
AB  - OBJECTIVE: To determine the time course and spatial distribution of uptake of
      macromolecules in the small intestine of rats subjected to cutaneous thermal
      injury. DESIGN: Prospective, controlled animal study. SUBJECTS: Fifty-five female
      Sprague-Dawley (CD) rats subjected to scald burn injury covering 20% (small
      injury; n = 29) and 40% (large injury; n = 6) of the total body surface area
      between 3 and 72 hrs after injury. Animals subjected to sham injury (n = 20) were
      used as controls. INTERVENTIONS: The intestine was cannulated near the distal
      ileum and incised 7 cm upstream. After perfusion with physiologic buffer, this
      intestinal loop was filled with the same buffer containing fluorescent-labeled
      dextrans (3 and 70 kilodaltons molecular weight) and ligated 4 cm from the
      injection point. After a 2-hr incubation period, the tissues were fixed with
      paraformaldehyde and cryosections were examined by laser confocal microscopy. The
      mesentery was also observed by laser confocal microscopy during incubation with
      the permeability probes. The disappearance of fluorescence was studied after
      washing the dextran probes from the gut lumen. MEASUREMENTS AND MAIN RESULTS: In
      small injuries, there was a transient uptake of the 3-kilodalton dextran by the
      epithelium in focal regions of the ileum with the effects seen between 7 and 21
      hrs after injury. In large injuries, epithelial staining was visible within 3
      hrs, and the marker was seen to translocate both to the lymphatics and the blood
      vessels of the mesentery. In comparison, the 70-kilodalton dextran was visible
      within the intercellular spaces. Little or no epithelial staining was seen in
      sham-injured animals. CONCLUSIONS: These results suggest that a transcellular
      pathway for the translocation of small macromolecules from the lumen to the
      mesentery can be activated after burn injury. The novel techniques described here
      will be useful to examine intestinal transport in various pathologic situations.

PMID- 7510223
TI  - Assignment of the human cytokeratin 3 gene (KRT3) to 12q12-->q13 by FISH.
AB  - We used fluorescence in situ hybridization to localize the human gene for
      cytokeratin 3 (KRT3), a member of the type II subfamily of cytokeratins, within
      the human genome. The results show that KRT3 is located within chromosome region
      12q12-->q13. All human type II keratin genes mapped to date have been assigned to
      chromosome 12, where they are likely to be organized into one homotypic cluster.

PMID- 7510225
TI  - Computational auditory scene analysis: listening to several things at once.
AB  - The problem of distinguishing particular sounds, such as conversation, against a
      background of irrelevant noise is a matter of common experience. Psychologists
      have studied it for some 40 years, but it is only comparatively recently that
      computer modelling of the phenomenon has been attempted. This article reviews
      progress made, possible practical applications, and prospects for the future.

PMID- 7510226
TI  - Transcription by T7 RNA polymerase of DNA containing abasic sites.
AB  - The effects of abasic (AP) sites on RNA synthesis were studied in vitro, using T7
      RNA polymerase and a plasmid template containing a T7 promoter. The presence of
      increasing numbers of AP sites caused a progressive decline in RNA synthesis. The
      average RNA chain length, calculated from the ratio of initiation to chain
      elongation, decreased with increasing numbers of AP sites, revealing that
      complete blocks must occur during synthesis. The probability that RNA polymerase
      would be blocked at an AP site in the DNA template strand was estimated to be 0.3
      in our experimental conditions. These results demonstrate that RNA synthesis by
      T7 RNA polymerase is inhibited by AP sites and that readthrough of the lesion
      occurs more frequently than premature chain termination. Chemical reduction of AP
      sites in the template did not change the block/bypass pattern.

PMID- 7510224
TI  - Angiogenic processes in the pathogenesis of human coronary atherosclerosis.

PMID- 7510227
TI  - Predominant induction of kinetochore-containing micronuclei by extracts of diesel
      exhaust particulates in cultured human lymphocytes.
AB  - The aneuploidy-inducing activity of extracts of diesel exhaust particulates from
      light duty (LD) and heavy duty (HD) engines was investigated in cultured
      peripheral blood lymphocytes of 8 healthy donors using the cytokinesis-block
      micronucleus test with the kinetochore labelling modification. A majority of the
      subjects tested showed a significant kinetochore-positive micronucleus induction
      after treatment with the highest dose (150 micrograms/ml) of LD extract, although
      some subjects also showed induction of kinetochore-negative micronuclei. Only one
      subject had significantly increased numbers of kinetochore-positive micronuclei
      at a dose of 400 micrograms/ml of HD extract. These results suggest that diesel
      extract, at least LD extract, possesses the ability to induce whole chromosome
      loss (aneuploidy) preferentially, although there are also chromosome breaks.

PMID- 7510229
TI  - Pore formation in artificial membranes by the secreted hemolysins of Proteus
      vulgaris and Morganella morganii.
AB  - Lipid-bilayer experiments were performed with the related hemolysins from Proteus
      vulgaris and Morganella morganii (HlyA). The addition of the toxins to the
      aqueous phase bathing lipid-bilayer membranes composed of different lipids
      resulted in the formation of transient ion-permeable channels. Membranes formed
      of pure lipids were rather inactive targets for the hemolysins as compared with
      lipid mixtures such as asolectin. The channels had several different substrates.
      The major open state had single-channel conductances of 500 pS in 0.15 M KCl at
      small transmembrane voltages. Experiments with different salts suggested that the
      hemolysin-induced channels of P. vulgaris and M. morganii were exclusively cation
      selective at neutral pH, caused by negative charges localized at the channel
      mouth. The mobility sequence of the cations within the channels was similar if
      not identical to their mobility sequence in the aqueous phase. The single-channel
      data were consistent with wide, water-filled channels with estimated minimal
      diameters of about 1 nm since the large organic cation Tris+ can permeate the
      channels without any detectable interaction with its interior. Pore-forming
      properties of these hemolysins were compared with those of HlyA of Escherichia
      coli. All these toxins share common features, oligomerize probably to form pores
      in lipid-bilayer membranes and form channels with similar properties which
      suggests that their structures are more or less identical.

PMID- 7510228
TI  - The carboxy-terminal peptide of detyrosinated alpha tubulin provides a minimal
      system to study the substrate specificity of tubulin-tyrosine ligase.
AB  - The ATP-dependent tubulin-tyrosine ligase (TTL) restores the carboxy-terminal
      tyrosine of alpha tubulin in alpha beta tubulin that has been previously
      detyrosinated. Here we show that the carboxy-terminal tetradecapeptide of
      detyrosinated alpha tubulin is used by TTL as a substrate, albeit at 50-fold
      lower efficiency than alpha beta tubulin. The minimal system provided by the
      TTL/peptide combination mirrors the TTL/tubulin system in all aspects tested, and
      shows a pronounced substrate inhibition. Synthetic peptides varying in length
      and/or containing single amino acid replacements were used to analyze the TTL
      specificity for the carboxy-terminal sequence of detyrosinated alpha tubulin.
      Peptides ending like alpha tubulin with the sequence Gly-Glu-Glu are optimally
      tyrosinated once a peptide length of 12 residues is reached. Position -1 of this
      recognition sequence, to which the tyrosine is added, must be glutamic acid.
      Position -2 accepts only an acidic amino acid but glutamic acid is by far
      preferred over aspartic acid. These results explain why a subpopulation of brain
      alpha tubulin, which ends with the sequence Gly-Glu, is not tyrosinated by TTL.
      The carboxy-terminal dodecapeptide of brain alpha tubulin with its polyglutamyl
      side-chain on position -6 shows the same substrate activity as the corresponding
      synthetic peptide lacking the side-chain. We discuss the substrate specificity of
      TTL for different alpha tubulins and speculate why tubulin is a better substrate
      than the optimal peptide covering the carboxy-terminal of detyrosinated alpha
      tubulin.

PMID- 7510230
TI  - Triple-helix formation interferes with the transcription and hinged DNA structure
      of the interferon-inducible 6-16 gene promoter.
AB  - The interferon responsive element (IRE) of the 6-16 gene lies within two 39-bp
      elements in tandem. A purine-rich oligodeoxynucleotide, oligo(dN), was found to
      be able to pair with the purine-rich strand of the IRE in an antiparallel
      orientation which led to triple-helix formation with Mg2+ being necessary for
      triplex stability. Footprinting analysis confirmed these results. The interaction
      between the IRE and the oligo(dN) was reversible and had a Kd equal to 20 nM. The
      two repeats of the 6-16 gene IRE can form a hinged DNA structure through pairing
      of their purine-rich regions; exonuclease III experiments support this model. The
      hybrid DNA structure leads to a parallel pairing of the purine strands of the 6
      16 gene IRE and this conformation was shown to be destabilized by triplex
      formation. When co-transfected with a reporter gene whose promoter was under the
      control of the 6-16 gene IRE, the triple-helix-forming oligo(dN)s inhibit the
      interferon-induced stimulation of the reporter gene with complete inhibition
      being obtained with 1 microM oligo(dN) at the time of transfection. When added to
      the cell culture medium after transfection, the concentrations of oligo(dN)
      needed to obtain 50% inhibition of the interferon effect on gene transcription
      must be 50-100 times higher. Besides the existence of a peculiar structure for
      the 6-16 gene IRE, the possibility of interfering with gene expression by means
      of oligo(dN)s is demonstrated.

PMID- 7510231
TI  - Leishmania major parasites share an epitope with the murine CD3-T cell receptor
      complex.
AB  - After immunization of BALB/c mice with a low molecular mass fraction (FrD; < or =
      31 kDa) isolated from a soluble extract of Leishmania major promastigotes, a
      panel of monoclonal antibodies (mAb) was obtained. One of these antibodies (mAb
      9C) recognized a cytosol-associated antigen from L. major of approximately 21 kDa
      as shown by Western blot and immunoprecipitation. In addition, mAb 9C reacted
      with surface structures of murine splenic T cells and T cell clones. Reactivity
      was confined to murine cells, but was not strain restricted. Immunoprecipitation
      studies and surface-labeling experiments with CD4+ T cell clones and the T cell
      receptor (TCR)-CD3-T cell line TG40 transfected with V alpha/beta chains from
      human TCR and concomitant co-expression of murine CD3 suggested that mAb 9C binds
      to an epitope located within the murine CD3-TCR complex. In addition, mAb 9C
      induced strong T cell proliferation. We conclude that L. major parasites share an
      epitope with the murine CD3-TCR complex which is functionally important for T
      cell activation.

PMID- 7510233
TI  - Failure of correlation between B7 expression and activation of interleukin-2
      secreting T cells.
AB  - It is well established that triggering interleukin-2 (IL-2) secretion by helper T
      cells requires the T cell to receive at least two discrete signals. One signal is
      transduced by the CD3 complex, usually as the result of T cell receptor (TcR)
      occupancy, the second, or co-stimulatory, signal involves a non-cognate
      interaction between cell surface accessory molecules on the antigen-presenting
      cell (APC) and the T cell. A molecular interaction that has been implicated in
      the provision of co-stimulatory signals is that between B7/BB1 on the APC and its
      ligands, CD28 and CTL-A4 on the T cell. We have studied the ability of HLA-class
      II antigen-positive human T cells and a population of DR1-expressing transfected
      human fibroblasts to stimulate a proliferative response by human T cell clones,
      and by freshly isolated peripheral blood T cells. Despite their high levels of B7
      expression, the T cell clones, were unable to induce proliferation or IL-2
      secretion by DR-restricted, antigen-specific T cells. In contrast, the DR1
      expressing transfectants, that were B7 negative, induced a strong proliferative
      response. When these two populations of DR-expressing cells were used to
      stimulate a primary alloresponse the results were reversed, in that the T cell
      clones induced a strong alloresponse but the transfected fibroblasts induced no
      proliferation. These results suggest that the expression of B7 may be necessary
      for costimulation of unprimed T cells, but not of established T cell clones.
      Furthermore the data show that the expression of B7 by an APC does not
      necessarily lead to IL-2 production or protection from the induction of
      tolerance. The mechanisms responsible for the inability of these T cells to
      provide full activation signals when used as APC is currently under
      investigation.

PMID- 7510232
TI  - Helper effector function of human T cells stimulated by anti-CD3 mAb can be
      enhanced by co-stimulatory signals and is partially dependent on CD40-CD40 ligand
      interaction.
AB  - In this study we have investigated whether anti-CD3-induced human T cell help for
      immunoglobulin production could be enhanced by co-stimulation of the T cells via
      other T cell surface molecules, and the contribution of CD40-CD40 ligand
      interaction to the execution of T helper effector function induced by these
      different stimulatory signals. In a system in which irradiated tonsillar T cells
      were stimulated with immobilized anti-CD3 monoclonal antibody (mAb), it was found
      that ligation of CD2 with a mitogenic pair of mAb considerably enhanced anti-CD3
      induced T cell help for immunoglobulin production. Likewise, ligation of CD28
      with mAb enhanced T helper activity, although to a lesser extent. Upon addition
      of anti-CD28 and anti-CD2 mAb together, an even higher immunoglobulin production
      was observed. This combination resulted in a four- to fivefold increase in
      immunoglobulin production as compared to cultures in which T cells were
      stimulated with anti-CD3 mAb alone. The effect of ligation with B7, the natural
      ligand of CD28, was studied in a system which utilizes the presentation of anti
      CD3 mAb on human Fc gamma RII-expressing mouse fibroblasts which were co
      transfected with human B7. It appeared that B7 could stimulate help for
      immunoglobulin production much more efficiently than ligation of CD28 with mAb
      did. Physical separation of B cells from T cells led to complete abrogation of
      immunoglobulin production. Blocking of CD40 with specific mAb, which have no
      intrinsic B cell stimulatory properties, or the CD40 ligand with a soluble CD40
      human IgM fusion protein, resulted in dose-dependent, but only partial,
      inhibition of T cell-dependent immunoglobulin production with all modes of T cell
      activation tested. A clear correlation was found between the induction of CD40
      ligand expression on the T cells by the different modes of co-stimulation and
      subsequent immunoglobulin production by the B cells. It is concluded that
      ligation of CD28 and/or CTLA-4, and of CD2 can generate co-stimulatory signals
      for T cell help for immunoglobulin production, which was found to be only
      partially dependent on the CD40-CD40 ligand interaction.

PMID- 7510235
TI  - Reversal of hyporesponsiveness in lpr CD4-CD8- T cells is achieved by induction
      of cell cycling and normalization of CD2 and p59fyn expression.
AB  - T cells freshly isolated from the peripheral lymph nodes of autoimmune MRL
      lpr/lpr (lpr) mice contain a large proportion of functionally non-mature T cell
      receptor (TcR)-alpha beta+CD3+CD2-CD4-CD8- T cells displaying the B cell isoform
      of CD45, B220. These cells are hyporesponsive as defined by minimal interleukin-2
      (IL-2) production and proliferation in response to stimulation. However,
      increased levels of inositol phosphates and a rapid mobilization of Ca2+ do occur
      upon stimulation of the TcR/CD3 complex. Furthermore, lpr CD4-CD8-T cells contain
      high levels of transcripts for the src-family tyrosine kinase p59fyn, and express
      a constitutively tyrosine-phosphorylated CD3-zeta chain. These features bear a
      certain resemblance to anergized T cells. These similarities are extended to show
      that culturing of lpr CD4-CD8- T cells in the presence of IL-2 in combination
      with phorbol 12-myristate 13-acetate and ionomycin initiates cell cycling and
      results in the gain of function; re-stimulation now yields IL-2-dependent
      proliferation in the absence of exogenous IL-2. In parallel with this gain in
      function, the population of cells obtained after 1 week in culture retains the
      TcR-alpha beta + CD4-CD8- phenotype, yet displays increased levels of CD2,
      decreased surface B220, and normal amounts of p59fyn-specific transcripts. These
      findings show that cell cycling is associated with the recovery of functional
      capabilities by lprCD4-CD8-T cells and is closely allied with surface CD2
      expression. Thus, the hyporesponsiveness of lpr T cells is not a fixed state.

PMID- 7510236
TI  - MRC OX19 recognizes the rat CD5 surface glycoprotein, but does not provide
      evidence for a population of CD5bright B cells.
AB  - To clone the rat CD5 gene we first produced two rat CD5 probes. The probes were
      obtained by polymerase chain reaction (PCR) on rat genomic DNA using primers
      designed on conserved regions between mouse and human CD5. The screening of a rat
      cDNA library at high stringency using these probes resulted in a 1.5-kb positive
      clone. The DNA sequence of this clone confirmed its CD5 nature, but the clone
      appeared to lack part of the 5' and part of the 3' end. These missing 5' and 3'
      ends were obtained by PCR on rat thymus RNA. By ligating these PCR products to
      the original 1.5-kb CDM8 clone, a full-length rat CD5 gene was constructed. The
      full-length clone showed high identity with mouse and human CD5; however, at the
      5' site of the gene a region of 36 nucleotides is present which is not seen in
      either mouse or human CD5. We have evidence that this sequence is a normal
      constituent of the rat CD5 gene: first, it is in frame with the rest of the CD5
      coding sequence; second, it does not contain a stop codon; and third, it is also
      present in the CD5 gene of other rat strains. We transfected the full-length CD5
      construct in COS cells and demonstrated that indeed the CD5 protein is recognized
      by MRC OX19. Although we showed that CD5 mRNA is present in rat B cells,
      extensive flow cytometry analysis using MRC OX19 as antibody failed to detect B
      cells expressing significant levels of CD5 on their cell surface compared to
      other B cells in any tissue or cell suspension tested from a variety of rat
      strains. This is in contrast with the mouse where a distinct population of B
      cells (B-1a cells) can be found expressing more CD5 than the other B cells.
      Either B-1 cells are not present in rats or CD5 is not the right phenotypic
      marker for rat B-1 cells. It still remains to be investigated whether a
      population of B cells with functions similar to those of murine B-1 cells is
      present in rats.

PMID- 7510234
TI  - Interleukin-3 and Bcl-2 cooperatively inhibit etoposide-induced apoptosis in a
      murine pre-B cell line.
AB  - Murine bone marrow-derived hemopoietic cells, dependent on interleukin (IL)-3 for
      their growth in culture, undergo programmed cell death, or apoptosis, upon
      cytokine withdrawal. The topoisomerase II inhibitor etoposide causes a more rapid
      onset of apoptosis in the IL-3-dependent cell line BAF3, deprived of IL-3. This
      acceleration of apoptosis by etoposide is prevented by inhibitors of RNA and
      protein synthesis and by the nucleases inhibitor aurintricarboxylic acid. The
      presence of IL-3 or overexpression of the oncogene bcl-2 caused a marked delay in
      the induction of apoptosis by etoposide, acting in a cooperative manner. The time
      at which the apoptotic program is irreversible is close to the induction of
      endonuclease activity as indicated by the effect of the delayed addition of
      either IL-3 or aurintricarboxylic acid on the onset of apoptosis, suggesting the
      importance of endonuclease activation in the development of apoptosis in
      hemopoietic cells.

PMID- 7510237
TI  - Targeted neutralization of the complement membrane attack complex inhibitor CD59
      on the surface of human melanoma cells.
AB  - Major problems in the immunotherapy of human tumors with complement-activating
      monoclonal antibodies (mAb) are (i) inherent resistance of tumor cells to
      complement cytolysis and (ii) a possible undiscriminatory attack against normal
      cells. In the present study we have developed a procedure to simultaneously
      direct the complement membrane attack complex and neutralize its inhibitor CD59
      (protectin) on human melanoma cells in vitro. G361 melanoma cells were
      selectively recognized in heterogenous cell mixtures by a complement-fixing mAb
      (R24) against the tumor cell GD3-ganglioside. Biotinylated anti-CD59 mAb
      (YTH53.1) was directed to the tumor cells with a high-affinity biotin-avidin
      bridge using a proportion of R24 as a biotinylated targeting mAb and avidin as a
      linker. Biotinylated anti-CD59 mAb lost its ability to activate complement, but
      retained its CD59-neutralizing activity. Thus, it was possible to avoid
      nonspecific lysis of surrounding erythrocytes and endothelial cells and direct
      the CD59-neutralizing effect to the tumor cells. As a result the tumor cells were
      efficiently killed by R24 plus complement while the bystander cells remained
      viable. These results suggest that it is possible to target an unrestricted
      complement membrane attack against GD3- and CD59-positive melanoma cells.

PMID- 7510238
TI  - Engagement of MHC class II molecules by staphylococcal superantigens activates
      src-type protein tyrosine kinases.
AB  - Staphylococcal exotoxins (SE) are superantigens that bind to monomorphic
      determinants on major histocompatibility complex (MHC) class II molecules and
      stimulate human peripheral blood T lymphocytes in a V beta-specific manner. SE
      also deliver activation signals via MHC class II molecules that initiate cell
      adhesion and cytokine gene transcription. These events are preceded by tyrosine
      phosphorylation and are antagonized by inhibitors of tyrosine kinases, indicating
      an essential role for these kinases in signaling via class II molecules. We
      report that stimulation of human peripheral blood monocytes with SE induced rapid
      and selective activation of the src-related protein tyrosine kinases (PTK) fgr
      and hck. SE also induced the activation of fgr and lyn in B cells. PTK activation
      by SE required MHC class II expression, and was greatly potentiated in the
      presence of T cells bearing toxin-specific V beta chains. These results indicate
      that in addition to their antigen and superantigen-presenting function, MHC class
      II molecules act as signal-transducing receptors that are coupled to src-type
      PTK.

PMID- 7510241
TI  - Proteolytic cleavage of CR1 on human erythrocytes in vivo: evidence for enhanced
      cleavage in AIDS.
AB  - The number of complement receptor type 1 (CR1; CD35) on human erythrocytes (E)
      decreases during normal in vivo aging. Patients with acquired immunodeficiency
      syndrome (AIDS) have an acquired deficiency of CR1 on E. The possible mechanisms
      responsible for the loss of CR1 from E include the release of small vesicles from
      the E membrane and proteolytic cleavage of CR1. When compared to E of normal
      donors and of asymptomatic human immunodeficiency virus HIV+ subjects, E of
      patients with AIDS had fewer CR1/E (p < 0.001), but had the same number of two
      glycosylphosphatidylinositol-anchored proteins, decay-accelerating-factor (DAF)
      and CD59. When compared to young E, old E separated by density gradients on
      Percoll had fewer CR1 [six normal subjects, mean loss: 50.4 +/- 4.9 (SEM) %], DAF
      (34.4 +/- 1.2%) and CD59 (34.5 +/- 2.7%). The loss of CR1 was significantly
      higher than the loss of DAF and CD59 (p < 0.02). In vitro, ATP depletion of E is
      responsible for the release of vesicles from the E surface, a reaction that has
      been called in vitro aging. CR1, DAF and CD59 were lost on ATP-depleted E;
      however, the loss of CR1 and DAF were identical (six experiments, mean loss of
      CR1: 28.7 +/- 2.7%, DAF: 26.3 +/- 4.6% and CD59: 20.5 +/- 4%). Thus, the release
      of vesicles from E cannot explain the specific loss of CR1 in patients with AIDS
      and would explain only incompletely the loss of CR1 during in vivo aging. In
      vitro experiments indicated that CR1 was more sensitive to trypsin and papain
      cleavage than DAF and CD59. Enhanced chemiluminescence Western blotting, using a
      monoclonal antibody (E11) recognizing fragments of CR1 down to 43 kDa on E
      exposed to trypsin or papain, indicated that normal E bear fragments of CR1,
      which are not found on polymorphonuclear leukocytes or on CR1-bearing vesicles in
      urine. The relative amount of these fragments was increased in patients with
      AIDS. Taken together these data suggest that the specific loss of CR1 on E in
      AIDS is due to proteolytic cleavage. The loss of CR1 during in vivo aging also
      involves proteolytic cleavage, although part of the loss might be explained by
      other mechanisms including the release of vesicles by E.

PMID- 7510239
TI  - Extracellular matrix components of the mouse thymus microenvironment. IV.
      Modulation of thymic nurse cells by extracellular matrix ligands and receptors.
AB  - Extracellular matrix (ECM) proteins can influence cell migration and
      differentiation in a variety of cell systems. Within the thymus, these molecules
      are heterogeneously distributed, and their physiological role is poorly
      understood. This prompted us to carry out in vitro studies using the thymic nurse
      cell (TNC) model. We observed that fibronectin and laminin accelerate spontaneous
      in vitro release of thymocytes from TNC, whereas anti-ECM antibodies exhibited a
      blocking effect. Similar results were obtained with anti-ECM receptor reagents.
      Moreover, these antibodies abrogated in vitro reconstitution of TNC complexes and
      thymocyte adhesion to TNC-derived epithelial cultures. Our results indicate that
      lymphocyte traffic in TNC (comprising both entrance into and exit from the
      epithelial structure) is affected by interactions involving extracellular matrix
      ligands and receptors. In this respect, the dynamic analysis of thymic nurse cell
      complexes should be regarded as a relevant in vitro tool for functional studies
      of distinct adhesion molecules in intrathymic lymphocyte traffic.

PMID- 7510240
TI  - The human OX40 homolog: cDNA structure, expression and chromosomal assignment of
      the ACT35 antigen.
AB  - Tissue distribution and expression on mitogen and virally stimulated lymphocytes
      render the ACT35 molecule a human lymphocyte activation antigen which as yet
      could not be clustered. Expression cloning of the ACT35 antigen from a pCDM8
      library of the HUT-102 cell line revealed strong homology of the cDNA and its
      encoded protein sequence with the formerly described rat OX40 antigen. The 1.4-kb
      nucleotide sequence and the deduced 277-amino acid sequence of the single
      transmembrane protein were 65% and 63% identical, in human and in rat,
      respectively. Conservation included one N-linked glycosylation site and one
      protein kinase C phosphorylation site. When expressed in COS-1 cells, the cDNA
      presented properties comparable to the native ACT35 antigen and the rat OX40
      molecule (relative molecular mass 48,000). Thus, the ACT35 protein corresponds to
      the hitherto unknown human OX40 antigen and is, therefore, another member of the
      tumor necrosis factor/nerve growth factor receptor (TNFR/NGFR) family. After
      applying fluorescence in situ hybridization, the human ACT35/OX40 gene could be
      mapped to chromosome band 1p36 and is, thus, linked to the genes for TNFR II and
      CD30.

PMID- 7510243
TI  - Leishmania major-specific CD8+ T cells are inducers and targets of nitric oxide
      produced by parasitized macrophages.
AB  - Lines of Leishmania major-specific CD8+ T cells were derived from the lymph nodes
      and spleens of CBA mice, immune following resolution of a primary infection, 7
      days after secondary challenge with viable L. major. Specific stimulation of
      these CD8+ T cells by bone marrow-derived macrophages infected with L. major led
      to the release of interferon-gamma by CD8+ T cells and nitric oxide by
      macrophages. Interestingly, the nitric oxide released by bone marrow-derived
      macrophages down-regulated the production of interferon-gamma by specifically
      activated CD8+ T cells. The proliferation and long-term maintenance of these
      parasite-specific CD8+ T cells was impaired by the nitric oxide produced by
      stimulating infected macrophages as a result of cytokines released by activated
      stimulating infected macrophages as a result of cytokines released by activated
      CD8+ T cells. Taken together, the results indicate that L. major-specific CD8+ T
      cells are sensitive to the toxic effect of the nitric oxide that they induce.

PMID- 7510244
TI  - Differential expression of APO-1 on human thymocytes: implications for negative
      selection?
AB  - Negative selection during T cell ontogeny involves selective induction of
      apoptosis in thymocytes. In peripheral lymphoid cells, apoptosis may be mediated
      via the APO-1 pathway. Here we report that APO-1 is constitutively expressed on
      the vast majority of human thymocytes but down-regulated at a mature stage of
      thymocyte development (TCR(hi)). This stage of development is characterized by
      CD28hi, CD44hi, CD69hi and up-regulation of Bcl-2 protein. We define a new
      thymocyte subpopulation that expresses high levels of APO-1 and intermediate
      levels of T cell receptor alpha/beta (TCR(im)/APO-1hi). The TCR(im)/APO-1hi
      population contains a large fraction of dead cells, suggesting that the APO-1
      pathway may be involved in negative selection of at least a fraction of
      thymocytes after intrathymic activation.

PMID- 7510242
TI  - Interleukin-7 regulates c-myc expression in murine T cells and thymocytes: a role
      for tyrosine kinase(s) and calcium mobilization.
AB  - Interleukin-7 (IL-7) was originally identified as a pre-B cell growth factor
      whose proliferating activity has been extended to numerous target cells including
      T lymphocytes. We investigated c-myc mRNA expression, an oncogene associated with
      proliferation, in the murine T cell line D10 G4.1 and freshly isolated thymocytes
      since both target cells proliferate in response to IL-7. We find that blockade of
      the tyrosine kinase pathway by genistein, a potent tyrosine kinase inhibitor,
      inhibits both IL-7-dependent D10 G4.1 cell proliferation and c-myc mRNA
      expression which appears to involve de novo mRNA synthesis and to be under the
      control of short-lived protein repressor(s). We have also examined possible
      signal transduction pathways which might regulate c-myc mRNA expression in the
      murine T cell line. IL-7 biological activity is not affected by stimulation of
      the protein kinase C pathway by phorbol esters. Thus, IL-7 regulates c-myc mRNA
      expression in a protein kinase C-independent manner and these data are
      strengthened by protein kinase C depletion which does not modify IL-7 c-myc mRNA
      responsiveness. In contrast and independent of protein kinase C activation,
      intracellular calcium mobilization by means of ionomycin reduces IL-7 induction
      of c-myc mRNA expression and may represent a physiological mechanism whereby IL-7
      bioactivity is regulated. The activity of IL-7 on c-myc mRNA expression has been
      extended to freshly isolated thymocytes and we find a synergistic effect of IL-7
      with concanavalin A. Taken together our results illuminate the molecular
      mechanism of IL-7 c-myc induction in the T lineage by ascribing a role for
      tyrosine kinase and increase in intracellular calcium in both IL-7 induced gene
      induction and cell proliferation.

PMID- 7510245
TI  - Coordinate induction of I kappa B alpha and NF kappa B genes.
AB  - The NF kappa B transcription factor exists in an inactive state when complexed
      with I kappa B alpha in the cytosol. Upon stimulation by a variety of agents, NF
      kappa B is released from I kappa B alpha and is translocated to the nucleus to
      induce kappa B motif-containing promoters. Once I kappa B alpha is dissociated
      from NF kappa B, I kappa B alpha is rapidly degraded. Few studies have been
      reported concerning the molecular basis for the regulation of I kappa B alpha
      gene expression. The current studies now show: (1) the expression of I kappa B
      alpha can be induced by protein synthesis inhibitors including cycloheximide,
      anisomycin, and puromycin; (2) cycloheximide-dependent induction can be blocked
      by a transcriptional inhibitor; (3) double-stranded RNA and tumor necrosis factor
      alpha, which are both known to induce NF kappa B, induce the expression of I
      kappa B alpha, whereas L-cysteine, which is known to inhibit NF kappa B
      expression, inhibits I kappa B alpha expression; and (4) the induction of I kappa
      B alpha gene expression is transient, as is the induction of other NF kappa B
      inducible genes. These findings suggest that I kappa B alpha is a NF kappa B
      inducible gene. The current results also show a concomitant induction of both
      subunits of NF kappa B (p50 and p65) after the treatment of cells with double
      stranded RNA. Based on these results, a model is proposed suggesting the
      existence of integrated pathways for the positive and negative autoregulation of
      I kappa B alpha and NF kappa B.

PMID- 7510246
TI  - An improved RT-PCR protocol for the quantitation of human retinoic acid receptor
      RNA.
AB  - A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) system
      has been developed to calculate the level of expression of human retinoic acid
      receptors (hRAR) alpha, beta, and gamma. Starting from a single cDNA preparation,
      the system allows the measurement of the number of molecules of each mRNA
      receptor. This is made possible by a synthetic internal standard mRNA which is
      added in known concentrations at the beginning of the reaction. The system is
      tested in a rhabdomyosarcoma cell line (A-673) where we have measured the
      upregulation of beta and gamma receptor mRNAs following treatment with retinoic
      acid.

PMID- 7510248
TI  - Induction of early response genes by hypergravity in cultured mouse osteoblastic
      cells (MC3T3-E1).
AB  - Hypergravity as low as 50g transiently stimulated cultured mouse osteoblastic
      cells (MC3T3-E1) to induce early response genes such as c-fos and egr-1, whereas
      expression of c-jun was marginally affected. The maximum induction of c-fos
      required more than 90g, but egr-1 induction became maximum below 50g.
      Staurosporin inhibited the induction of c-fos by hypergravity almost completely
      at a concentration of 0.1 microM, but it inhibited the induction of egr-1 only
      partially. In cells pretreated with 12-O-tetradecanoylphorbol 13-acetate,
      induction of c-fos by hypergravity was almost completely abolished, whereas that
      of egr-1 was not affected. Activity of protein kinase C seemed to be activated in
      cells centrifuged at 900g. These results indicate that hypergravity stimulates
      multiple signal transduction cascades that are connected with the expression of
      early response genes.

PMID- 7510247
TI  - Exclusion of specific human chromosomes into micronuclei by 5-azacytidine
      treatment of lymphocyte cultures.
AB  - Lymphocyte cultures of a male proband were treated with 5-azacytidine. This
      cytidine analogue induces distinct undercondensation in the heterochromatic
      regions of chromosomes 1, 9, 15, 16, and Y and increases the frequency of
      micronuclei formation. In order to analyze the chromosomal content of these
      micronuclei, in situ hybridizations with biotinylated probes specific for
      chromosomes 1, 9, 15, 16, and Y were performed. Probes for chromosomes 11, 17,
      and X were used as controls. Each of 5000 hybridized cell nuclei was scored for
      associated micronuclei, and signal distribution was documented. In preparations
      hybridized with probes detecting the 5-azacytidine-sensitive chromosomes a
      significant fraction of micronuclei showed hybridizations. In contrast,
      micronuclei in preparations probed for chromosomes 11, 17, and X lacked
      hybridization signals. The results suggest that in 5-azacytidine-treated cultures
      the 5-azacytidine-sensitive chromosomes are preferentially excluded into the
      micronuclei.

PMID- 7510249
TI  - Expression, glycosylation, and phosphorylation of human keratins 8 and 18 in
      insect cells.
AB  - The filament forming ability and post-translational modifications of the human
      intermediate filaments, keratin polypeptides 8 and 18 (K8/18), were studied in
      recombinant baculovirus-infected insect (Spodoptera frugiperda, Sf9) cells. No
      change in cell morphology was noted after high levels of K8/18 were expressed in
      Sf9 cells coinfected with recombinant virus-containing human K8 and K18.
      Immunofluorescence staining showed that K8/18 expressed in Sf9 cells formed
      somewhat what disorganized and rope-like filaments, in contrast with K8 or K18
      expression alone, which did not result in filament formation. K8/18 expressed in
      Sf9 cells were glycosylated (O-linked N-acetylglucosamine) and phosphorylated,
      and each modification occurred on different molecules of K8 and K18, as
      previously found in human HT29 cells. The glycosylation and phosphorylation of
      K18 in human and insect cells were very similar as determined by tryptic peptide
      mapping and localization to the head and proximal rod domains. In contrast,
      differences were noted in the relative intensity of the tryptic phospho- and
      glycopeptides of K8 expressed in human and insect cells and in the ratio of K8 to
      K18 phosphorylation in human and insect cells. Our results show that although
      quantitative differences exist, the post-translational modification of K8/18
      expressed in insect cells is quite similar to its mammalian counterpart,
      especially for K18. Baculovirus expressed K8/18 should prove useful for mapping
      phosphorylation and glycosylation sites and for studying factors involved in
      organized filament assembly in mammalian cells.

PMID- 7510250
TI  - Inhibition of topoisomerase II activity and its effect on nucleolar structure and
      function.
AB  - The relationship between topoisomerase II activity and ribosomal RNA synthesis
      was investigated using the antitumoral drug VM26, a specific inhibitor of
      topoisomerase II. For this purpose TG cells, a human tumor cell line, were
      cultured in the presence of 2.5 microM VM26 for 1 and 3 h; VM26 reduced the
      topoisomerase II activity, measured in whole cell extracts. In the presence of
      VM26 the [3H]uridine incorporation into ribosomal RNA was decreased; electron
      microscopy investigation of nucleoli showed a segregation of nucleolar
      components. Because VM26 stabilizes the cleavable complex and inhibits the
      resealing reaction, thus causing potential cleavage sites, we have analyzed the
      double-strand breaks caused by the drug treatment in the tandem repeat ribosomal
      DNA (rDNA) genes, by indirect labeling with two probes recognizing the 5' portion
      of ETS (BES) and the 3' portion of 28S (LS6BE) transcribed gene. In VM26-treated
      cells rDNA is fragmented and a topoisomerase II preferential cleavage site is
      present, localized at 1.85 kb in 28S region from 3' EcoRI site.

PMID- 7510253
TI  - Distribution of phosphorylated microtubule-associated protein 1B during neurite
      outgrowth in PC12 cells.
AB  - The functional significance of microtubule-associated protein 1B (MAP1B)
      phosphorylation during neuronal differentiation is unknown. In the present study
      we examined the hypothesis that the phosphorylation of MAP1B is required for
      neurite outgrowth. We reasoned that if MAP1B phosphorylation was important for
      neurite outgrowth then the intracellular distribution of phosphorylated MAP1B
      might exist as a discrete subset of the pattern for total MAP1B. We utilized a
      monoclonal antibody (mAb 7-1.1) that specifically recognizes a phosphorylated
      epitope on MAP1B and a polyclonal antiserum that recognizes all MAP1B protein to
      compare the distributions of phosphorylated and total MAP1B during neurite
      outgrowth. Phosphorylated MAP1B progressively accumulated in both the soluble and
      cytoskeletal fractions of differentiating cells. Similar proportions of total and
      phosphorylated MAP1B were associated with the cytoskeletons of differentiating
      PC12 cells. Within individual cells, phosphorylated MAP1B, in comparison with
      total MAP1B, was not limited to a particular intracellular domain. Phosphorylated
      MAP1B was present in both neurites and cell bodies. It was associated with
      fibrillar microtubules in neurites and growth cones, but it appeared nonfibrillar
      within cell bodies. In some cells that differentiated rapidly, there was little
      phosphorylated MAP1B in the early neurites despite the presence of extensive
      microtubules. In addition, although phosphorylated MAP1B increased in populations
      of mature PC12 cell cultures, increases in phosphorylated MAP1B did not always
      correlate with neurite outgrowth in individual cells. These results suggest that
      the phosphorylated isoform of MAP1B recognized by mAb 7-1.1 may not be required
      for neurite outgrowth.

PMID- 7510252
TI  - Comparison of defolliculated oocytes and intact follicles of the cockroach using
      the vibrating probe to record steady currents.
AB  - Follicle cells were removed by dissection from early vitellogenic oocytes of the
      cockroach Blattella germanica. The vibrating probe was used to record steady
      currents from 19 defolliculated oocytes and 19 intact follicles of the same
      developmental stage. Defolliculated oocytes generated currents that were stable
      and distinguishable (by intensity or selective direction) from background
      reference values. Distributions of the intensities of reference values and
      experimental values were, in general, similar in both intact and defolliculated
      preparations. The patterns of currents generated by preparations recorded in the
      mid-sagittal plane were analyzed for both defolliculated oocytes (n = 8) and
      intact follicles (n = 10). The larger, generally more mature preparations in both
      groups generated patterns of current similar to the pattern seen in mid
      vitellogenic follicles (focused inward near the germinal vesicle (GV), the
      presumptive ventral side, and broadly outward on the apo-GV side, the presumptive
      dorsal side). Smaller sized preparations in both groups showed inward or outward
      current on the apo-GV aspect and, typically, inward current at the GV. Only two
      defolliculated oocytes, and no intact follicles, appeared to generate outward
      current at the GV, and we believe this observation resulted from recording
      slightly outside the mid-sagittal plane. We conclude that preparations during
      early-vitellogenesis initially generate currents without an asymmetric pattern
      and that the inward flux at the GV is the first step in developing patterns of
      currents. The results suggest that the oocyte (and not the follicle cell
      epithelium) is responsible for generating the various patterns of currents
      observed in early-vitellogenic stages. At the end of early-vitellogenesis, the
      follicle cell epithelium begins to adhere tightly to the oocyte. The possibility
      is considered that the follicle cells may influence the currents generated during
      mid-vitellogenesis.

PMID- 7510254
TI  - A novel NK-related mouse homeobox gene: expression in central and peripheral
      nervous structures during embryonic development.
AB  - We have identified three novel mouse homeobox genes that are related to the
      Drosophila NK gene family. Two genes without direct homologues in Drosophila were
      designated Nkx-5.1 and Nkx-5.2; the third gene Nkx-1.1 constitutes the mouse
      homologue to NK1.Nkx-5.1 and Nkx-5.2 are closely linked on mouse chromosome 7,
      whereas Nkx-1.1 is located on a different chromosome. Here, we report the
      spatiotemporal expression pattern of Nkx-5.1 during prenatal mouse development.
      Nkx-5.1 gene activity begins at Embryonic Day 10.5 in the developing ear, the
      neural tube, and dorsal root ganglia. It continues to be active throughout
      prenatal life in discrete regions of the brain with an anterior border in the
      ventral diencephalon at the optic chiasma and expression domains in
      mesencephalon, metencephalon, and myelencephalon. At midgestation, Nkx-5.1 is
      also expressed in mesenchyme of the head and branchial arches, and in some
      cranial ganglia, as well as in derivatives of neural crest, such as the truncus
      sympathicus and myenteric ganglia. The time pattern of Nkx-5.1 expression and its
      confinement to primarily postmitotic cells of the central and peripheral nervous
      system suggest that Nkx-5.1 may play a role in the specification of neuronal cell
      types.

PMID- 7510255
TI  - The alpha subunit of RNA polymerase specifically inhibits expression of the porin
      genes ompF and ompC in vivo and in vitro in Escherichia coli.
AB  - Overproduction of the alpha subunit of RNA polymerase in Escherichia coli
      resulted in inhibition of transcription of two osmoregulated porin genes, ompF
      and ompC, but not of constitutively expressed housekeeping genes. Overproduction
      of the sigma subunit did not have any inhibitory effects. The specific inhibitory
      effect of the alpha subunit was also found to depend upon the OmpR protein, the
      transcriptional activator for ompF and ompC. These results are in general
      agreement with other biochemical and genetic evidence suggesting that the alpha
      subunit is the subunit of RNA polymerase that directly interacts with certain
      transcriptional activators to initiate transcription.

PMID- 7510251
TI  - SV40-transformed human cells in crisis exhibit changes that occur in normal
      cellular senescence.
AB  - SV40 T antigen can induce senescent human diploid fibroblasts to synthesize DNA;
      however, the cells fail to go through mitosis. In this study, we examined the
      expression of the cdc2 and cyclin B genes, which are required for completion of
      mitosis, to determine whether defects in their expression occurred when SV40
      transformed human cells entered the phase of crisis. If defects were observed it
      would indicate that immortalization by the virus involved reexpression of these
      genes. We found that the expression of cdc2 was unimpaired at both the RNA and
      protein levels, but that cyclin B expression was decreased in cells in crisis
      when compared with precrisis (mortal) and postcrisis (immortal) cells. Tritiated
      thymidine uptake demonstrated that the majority of cells in crisis were not
      actively cycling. Consistent with the latter observation we found that cyclin A,
      which is required for cells to traverse through S to G2, was downregulated in
      these cells. Since many of the results obtained with cells in crisis were similar
      to what is observed in normal human cells when they become senescent, we analyzed
      the expression of the genes fibronectin and sdi1 (a gene recently cloned from
      senescent cells that codes for an inhibitor of DNA synthesis). Both genes were
      overexpressed in cells during crisis, as is the case with senescent cells. The
      results are discussed in terms of the two-stage model previously proposed to
      explain the process of immortalization of human diploid fibroblasts by SV40.

PMID- 7510256
TI  - Structural relationship between the S1 and S4 subunits of pertussis toxin.
AB  - Pertussis toxin, the most important protective antigen of Bordetella pertussis,
      is a 106-kDa hexameric protein composed of an A-protomer (subunit S1) and a
      pentameric B-oligomer (S2 + S3 + 2S4 + S5). The most potent mouse-protective
      monoclonal antibodies against both respiratory and intracerebral infections were
      specified for either S1 or S4 and competed with each other in binding to epitopes
      of native pertussis toxin captured by haptoglobin or in solution, although they
      did not compete on unfolded pertussis toxin. These data suggest that the
      protective epitope(s) of S1 and S4 are very closely correlated; they are probably
      close together sterically. Non-protective anti-S1 and anti-S4 monoclonal
      antibodies recognized inner antigenic determinants which are not exposed on the
      surface of native pertussis toxin and interfered with association of the A
      protomer and the B-oligomer. These data suggest that the A-protomer and the S4
      subunit of the B-oligomer may be closely associated in the native hexameric
      pertussis toxin molecule.

PMID- 7510257
TI  - Distinct molecular mechanism regulate cell cycle timing at successive stages of
      Drosophila embryogenesis.
AB  - The conserved regulators of cell cycle progression--Cyclins, Cdc2 kinase, and
      String phosphatase (Cdc25)--accommodate multiple modes of regulation during
      Drosophila embryogenesis. During cell cycles 2-7, Cdc2/Cyclin complexes are
      continuously present and show little fluctuation in abundance,
      phosphomodification, or activity. This suggests that cycling of the mitotic
      apparatus does not require cytoplasmic oscillations of known regulatory
      activities. During cycles 8-13 a progressive increase in the degradation of
      Cyclins at mitosis leads to increasing oscillations of Cdc2 kinase activity.
      Mutants deficient in cyclin mRNAs suffer cell cycle delays during this period,
      suggesting that Cyclin accumulation times these cycles. During interphase 14,
      programmed degradation of maternal String protein leads to inhibitory
      phosphorylation of Cdc2 and cell cycle arrest. Subsequently, mitoses 14-16 are
      triggered by pulses of zygotic string transcription.

PMID- 7510258
TI  - Isolation and characterization of two genes encoding calitoxins, neurotoxic
      peptides from Calliactis parasitica (Cnidaria).
AB  - Among sea anemone neurotoxins, calitoxin, recently isolated from Calliactis
      parasitica, is a highly toxic peptide of 46 amino acids (aa), whose sequence
      differs greatly from that of all sea anemone toxins isolated so far. In this
      study, two genes (clx-1 and clx-2) coding for two highly homologous calitoxins
      were isolated and characterized from a C. parasitica genomic library. The clx-1
      gene encodes the already known calitoxin sequence, named CLX-I, whereas a single
      bp substitution in the coding region of clx-2 is responsible for a single Glu6-
      >Lys replacement in a new peptide named CLX-II. The structural organization of
      the two genes is very similar: two introns and three exons, whose sequences are
      highly homologous for clx-1 and clx-2 (95% identity). The open reading frame
      (ORF) of both clx-1 and clx-2 codes for a precursor peptide of 79 aa, whose N
      terminus has the feature of a single peptide, while the C-terminus corresponds to
      the sequences of mature CLX-I and CLX-II. The finding that a pair of basic aa is
      located upstream from the sequence of both mature toxins strongly suggests that
      proteolytic events, at specific cleavage sites, are responsible for the release
      of neurotoxins from their respective precursor molecules.

PMID- 7510260
TI  - The complete sequence of the gene encoding mouse cytokeratin 15.
AB  - To characterize the type-I keratin-encoding gene family around the mouse keratin
      19-encoding gene (K19, EndoC), which encodes simple epithelial-type cytokeratin
      (CK), we screened a mouse genomic library by hybridization to a K19 cDNA probe.
      One clone of 16 kb contained the second to the sixth exons of K19 and the other
      keratin-encoding gene was located about 4 kb downstream from K19. Sequencing,
      Northern hybridization and genomic Southern blotting revealed that the downstream
      gene encodes the mouse K15 gene. This gene consists of eight exons and the
      positions of the introns coincide with those of other type-I keratin-encoding
      genes. The 5' upstream regions of the mouse and human K15 genes contain
      homologous sequences around the respective TATA boxes, suggesting that the same
      factors are involved in the regulation of their transcription.

PMID- 7510259
TI  - Isolation of a cDNA encoding the chicken p50B/p97 (Lyt-10) transcription factor.
AB  - NF-kappa B is a transcription factor composed of the p50 and p65 subunits. Recent
      works identified another human gene which encodes a molecule related to the p50
      subunit, termed p50B, p49 or lyt-10. Here, we isolated the cDNA clones encoding
      chicken p50B/p97 (Lyt-10). The deduced amino acid sequence of the precursor
      protein, p97, shows conservation of the overall structure, and 86% identity in
      the Rel homology domain (RHD) and 56% identity in the ankyrin repeat domain (ARD)
      to human p50B/p97. Expression of this gene is highest in the chicken spleen.

PMID- 7510261
TI  - Cloning of FRK, a novel human intracellular SRC-like tyrosine kinase-encoding
      gene.
AB  - We report the cloning of a novel tyrosine kinase (TyK)-encoding gene (TYK) from
      the human hepatoma cell line Hep3B. Using the polymerase chain reaction (PCR) and
      oligodeoxyribonucleotide primers based on conserved TYK motifs, a 180-bp fragment
      was cloned and used to obtain full-length cDNA clones of 2.9 kb, with an open
      reading frame of 505 amino acids (aa). Restricted expression was detected by
      Northern blotting or reverse-transcribed PCR in a broad range of cell lines. The
      predicted aa sequence contains characteristic TyK motifs without a transmembrane
      region, suggesting an intracellular localization. There was 49% aa sequence
      identity with human FYN product and 47% with human SRC product; however, several
      structural differences distinguish this clone from other SRC subfamily members.
      This clone, FYN-related kinase or FRK, is a novel member of the intracellular TYK
      gene family.

PMID- 7510262
TI  - Directed mutagenesis of a regulatory palindromic sequence upstream from the
      Brevibacterium lactofermentum tryptophan operon.
AB  - A cloned 9.6-kb fragment of Brevibacterium lactofermentum DNA, carrying the
      entire trp operon and upstream regulatory sequences, produces a polycistronic 7.0
      kb transcript as detected by hybridization with an internal probe. The
      transcription start point (tsp) was identified by S1 mapping. The operator
      promoter (OP) region subcloned in Escherichia coli and B. lactofermentum promoter
      probe vectors exhibited about tenfold higher activity in B. lactofermentum. A 14
      bp wild-type (wt) palindrome located at bp -15 to -28 was mutated to change the
      conserved adenine adjacent to the axis of symmetry. The wt and mutated OP regions
      were coupled to the amy reporter gene (encoding alpha-amylase [Amy]) or to the 5'
      region (trpE and trpG genes) of the trp operon, for expression studies.
      Constructions with the regulatory signals coupled to the wt trpE-trpG genes were
      introduced in a B. lactofermentum trpE mutant (obtained by gene disruption). The
      mutation in the palindrome did not affect the promoter activity in B.
      lactofermentum or E. coli when grown in minimal medium. Tryptophan repressed the
      OP as assayed by the anthranilate synthase (AS) activity in B. lactofermentum in
      constructions with the wt OP region, but surprisingly, caused a large stimulation
      of either AS or the Amy reporter activity, in constructions with the mutated OP.
      The palindromic sequence is, therefore, involved in a dual repression-stimulation
      control of expression of the trp operon.

PMID- 7510263
TI  - A new highly polymorphic DNA restriction site marker in the 5' region of the
      human tyrosine hydroxylase gene (TH) detecting loss of heterozygosity in human
      embryonal rhabdomyosarcoma.
AB  - We have isolated a new marker (cos11-5TH) that detects an MspI restriction
      fragment length polymorphism in the 5' region of the human tyrosine hydroxylase
      gene (TH) on chromosome band 11p15.5. This region of human chromosome 11 contains
      several important loci for disease phenotypes including Beckwith-Wiedemann
      syndrome (BWS), Wilms' tumor, and embryonal rhabdomyosarcoma. Thus,
      identification of new polymorphic markers in this region are important for future
      gene mapping and linkage analyses. To better define the region of 11p15.5 deleted
      in embryonal rhabdomyosarcoma, this new marker was used to investigate allelic
      losses in embryonal rhabdomyosarcoma tumors.

PMID- 7510265
TI  - Blood lymphocytes of autoimmune disease patients receiving FK506 exhibit normal
      ex vivo cytokine gene expression and proliferative responses.
AB  - It is well recognized that FK506 (Tacrolimus) is a powerful inhibitor of CD4+ T
      cell activation and proliferation in vitro. In this study, immunophenotypic and
      functional analyses were performed on peripheral blood mononuclear cells from a
      total of 30 patients with various autoimmune disorders before and whilst the
      patients were receiving systemic FK506 therapy. The expression of cell surface IL
      2R alpha and -beta on CD4+ and CD8+ cells, cytokine message (IL-2, IFN-gamma, IL
      4, IL-10) and the proliferative activity of lymphocytes in response to rIL-2 were
      examined. Despite plasma levels of FK506 compatible with the blockade of IL-2
      production by stimulated T cells in vitro, cells from patients on FK506 treatment
      cultured ex vivo with either ConA or IL-2 did not differ from normal cells in
      their expression of cytokine mRNA or their proliferative responses. These data
      indicate that the presumed in vivo suppression of T-cell function by FK506 is
      rapidly reversible ex vivo. Alternatively/additionally, they suggest that FK506
      may mediate its in vivo action primarily by mechanisms other than blockade of T
      cell function.

PMID- 7510266
TI  - Regulation by PGE2 of IL-2, IL-3 and IFN production by cortico-resistant
      thymocytes.
AB  - We have investigated the role of prostaglandin E2 (PGE2) in the regulation of
      cytokine release (IL-2, IL-3 and IFN) by cortico-resistant thymocytes (CRT)
      stimulated or not through the T-cell antigen receptor by an anti-CD3 monoclonal
      antibody (mAb). CRT were found to spontaneously produce IL-2 and IL-3 on day 4 of
      culture, but not IFN. After activation with an anti-CD3 mAb, the maximal levels
      for IL-2 and IFN were observed on day 1 and for IL-3 on day 4. Addition of PGE2
      inhibits IL-2 production and has no effect on IFN production. Indomethacin, an
      inhibitor of the cyclooxygenase pathway, enhanced both IL-2 and IFN production.
      In contrast, IL-3 secretion by anti-CD3 activated CRT was up-regulated by PGE2,
      and its level was decreased in the presence of indomethacin in both stimulated or
      unstimulated cells. As has been observed with PGE2, forskolin which activates
      adenylate cyclase increases the IL-3 level. Thus PGE2 may interfere in the
      process of thymocyte proliferation and/or differentiation by regulating
      differentially the interleukin production.

PMID- 7510264
TI  - An additional HpaII polymorphism in exon 2 of the human platelet membrane
      glycoprotein IIIa gene.
AB  - A novel HpaII polymorphic site caused by a T-->G transversion at codon 40 of the
      GP3a locus is described. It was found together with another polymorphic HpaII
      site at codon 33. Both are associated with the immunologically defined HPA-1b
      antigen.

PMID- 7510268
TI  - Frozen section diagnosis in ophthalmic pathology.
AB  - Frozen section diagnosis is extensively used in various branches of pathology,
      but its application in ophthalmic pathology was recognised only in the 1970s. We
      studied 10 sections of ocular and adenexal lesions by frozen section diagnosis,
      which included orbital lesions (4 cases), lid lesions (3 cases), and intraocular
      tissue (1 case). The time taken for processing ranged between 10 to 15 minutes.
      Diagnoses based on frozen section evaluation included lymphoma, mesenchymal
      chondrosarcoma, solar keratosis, compound naevus, silicone oil globules in
      cataractous lens, neurofibromatosis, pseudotumour, retinoblastoma, and chronic
      blepharitis. Although further histopathologic examination correlated well with
      the frozen section (100%) observations, the diagnosis was deferred in the case of
      naevus and reactive lymphoid hyperplasia. Our study shows that frozen section
      diagnosis in ophthalmic surgery is quite reliable and is particularly useful in
      ocular adenexal lesions.

PMID- 7510267
TI  - Emergence of a radioresistant population of co-stimulatory splenocytes during
      remission of experimental autoimmune encephalomyelitis in Lewis rats.
AB  - T-cell hybridomas specific for myelin basic protein (MBP) were used to assess
      regulation of co-stimulatory signals during remission of experimental autoimmune
      encephalomyelitis (EAE) in Lewis rats. Both THYB-1 and THYB-2 subsets of T-cell
      hybridomas recognize class II major histocompatibility complex-restricted
      determinants in the 72-86 encephalitogenic region of MBP. However, THYB-2 hybrids
      uniquely express additional requirements for co-stimulatory signals from
      radiosensitive splenocytes (SPL) to support the response of MBP-stimulated IL-2
      production. Hence, this subset provides a means to study regulation of THYB-2
      specific co-stimulatory signals during the course of EAE. This study revealed
      that sensitization of Lewis rats with MBP in complete Freund's adjuvant induced a
      radioresistant subpopulation of co-stimulatory SPL that emerged during the
      remission phase of EAE. These radioresistant SPL provided specific accessory cell
      activities that fulfilled the co-stimulatory requirements of THYB-2 hybrids.
      These findings support the hypothesis that in vivo activation events elicit
      radioresistance in an emergent clonally expanding population of antigen-specific
      lymphocytes. A central prediction of this hypothesis is that cellular activation
      should confer radioresistance to co-stimulatory lymphocytes. This prediction was
      verified by the observation that in vitro activation of naive SPL with different
      B- and T-cell mitogens conferred radioresistance to co-stimulatory SPL. Mitogenic
      activation not only induced radioresistance but also dramatically augmented co
      stimulatory activity of purified B cells. In summary, the results of this study
      support the hypothesis that in vivo activation of co-stimulatory lymphocytes may
      regulate activities of encephalitogenic T-helper cells during progression and
      remission of EAE.

PMID- 7510269
TI  - Calcium entry blockers stimulate vasoproliferation on the chick chorioallantoic
      membrane.
AB  - The effect of three calcium entry blockers, nifedipine, nimodipine, and verapamil
      on the vascular density of the chick chorioallantoic membrane (CAM) was studied.
      Each compound was released onto the CAM for three days (Days 7-10 or Days 11-14
      of incubation) from Elvax polymer sustained release pellets. Quantitation of the
      vascular density was obtained by counting the number of intercepts between the
      CAM vessels and a series of concentric circles placed over the CAM; the results
      are expressed as a vascular density index (VDI). Nifedipine released during Days
      11-14 elicited an inverted U-shaped dose-response curve in the VDI with a peak
      increase of 30.6% over the control. Nimodipine induced a similar, but less
      intense (16.9%) increase in the VDI. Peak responses for both compounds occurred
      with pellets containing 0.15 microgram of the drug. Verapamil stimulated a VDI
      increase equivalent to nimodipine, but the response was not dose-related. Neither
      nifedipine nor nimodipine caused a significant increase of the VDI during Days 7
      10. Verapamil was not tested at this time. The calcium channel agonist, BAY K
      8644, did not alter the VDI; however, the vasoproliferative response to
      nifedipine (0.15 microgram/pellet) was reduced 70% when an equal mass of BAY K
      8644 was incorporated also into the pellet. These experiments demonstrate a
      vasoproliferative effect for the three calcium entry blockers, and support an
      hypothesis that their efficacy in the treatment of cardio/cerebro-vascular
      disease resides, in part, in their capacity to stimulate new blood vessel growth.

PMID- 7510271
TI  - Precocious IRBP gene expression during mouse development.
AB  - PURPOSE: To determine if the time course for the onset of gene and protein
      expression for interphotoreceptor binding protein (IRBP) precedes that of opsin
      in the developing mouse retina. METHODS: Relative mRNA levels of the IRBP and
      opsin genes were determined in prenatal and postnatal retinal RNA with RNase
      protection analysis (RPA). To determine if IRBP and opsin protein expressions are
      differentially regulated, dissociated retinal cells from postnatal (P) days 2 and
      3 mice, that were injected with BrdU, were then double-labeled with antibodies
      against BrdU and either opsin or IRBP. RESULTS: With RPA, IRBP mRNA was detected
      on embryonic (E) day 11 at the time of cone formation, whereas opsin mRNA was not
      detected until P0. It took until P3 for opsin expression to reach significant
      levels, whereas rods already appear during embryonic development. IBRP
      transcription preceded that of opsin because it rapidly increased from E13 to an
      early postnatal day. By P20, the expression levels of IRBP and opsin achieved
      constancy. Double antibody labeling revealed positive staining for both IRBP and
      BrdU as soon as 2 hours after injection, but it took until 40 hours for double
      positive staining for opsin and BrdU. CONCLUSION: Because only IRBP protein
      expression was observed before the last mitosis of the photoreceptor precursor
      cells, IRBP could be essential for retinal development.

PMID- 7510270
TI  - Staining characteristics and antiviral activity of sulforhodamine B and lissamine
      green B.
AB  - PURPOSE: Fluorescein and rose bengal are dyes used routinely in the examination
      of the ocular surface. As part of an ongoing search for a superior ophthalmic dye
      with optimal specificity and sensitivity and a lack of interference with
      subsequent viral cultures, and as part of studies that use chemical dyes to
      understand better the pathophysiology of ocular surface disorders, the staining
      characteristics and antiviral activity of sulforhodamine B and lissamine green B
      were investigated. METHODS: Staining of rabbit corneal epithelial cell cultures
      by sulforhodamine B and lissamine green B was compared to that of fluorescein and
      rose bengal. Diffusion of each dye through a collagen gel was measured. Uptake of
      lissamine green B by herpes simplex virus type 1 (HSV-1)-infected Vero cell
      cultures was compared at several times postinfection. The effect of
      sulforhodamine B and lissamine green B on HSV-1 plaque formation in Vero cells
      was determined. The cellular toxicity of sulforhodamine B and lissamine green B
      in vitro was examined by a quantitative 14C-amino acid uptake assay and by a
      qualitative cell viability assay. Finally, the effect of sulforhodamine B and
      lissamine green B on viral replication was compared in vivo with that of rose
      bengal in a rabbit model of herpetic epithelial keratitis. RESULTS: Rose bengal
      vividly stained cell monolayers of explant cultures of rabbit corneal epithelium.
      By light microscopy, sulforhodamine B and lissamine green B, like fluorescein,
      did not stain the epithelial cells, but did stain the corneal explant stroma.
      Pretreatment of epithelial cells with 0.25% trypsin for 5 minutes failed to
      induce dye uptake; however, pretreatment with 0.5% Triton X-100 for 5 minutes
      resulted in nuclear staining by lissamine green B, but not sulforhodamine B. When
      added to a collagen gel, the relative diffusion rate was fluorescein > lissamine
      green B > sulforhodamine B > rose bengal. By spectrophotometric analysis, HSV-1
      infected and uninfected Vero cells bound equivalent amounts of lissamine green B
      until late in infection, when infected cells took up more dye (P < 0.001). A
      direct neutralization assay showed that 0.06% lissamine green B or 0.5%
      sulforhodamine B reduced HSV-1 plaque formation in Vero cells by greater than
      50%, when present at the time of viral adsorption. By a quantitative 14C-amino
      acid uptake assay, lissamine green B was toxic to Vero cells in a dose-dependent
      manner, whereas sulforhodamine B was relatively nontoxic at the concentrations
      tested. By a cell viability assay, however, neither dye showed significant
      cellular toxicity. In a rabbit model of herpetic epithelial keratitis, rose
      bengal significantly reduced viral replication and recovery, whereas
      sulforhodamine B and lissamine green B had no effect. CONCLUSIONS: Neither
      sulforhodamine B nor lissamine green B stain healthy, normal cells. Lissamine
      green B stains membrane-damaged epithelial cells, but sulforhodamine B does not.
      Both sulforhodamine B and lissamine green B stain corneal stroma. Lissamine green
      B inhibits HSV-1 plaque formation at low concentrations of dye in vitro, which
      correlates with suppression of cellular metabolism as demonstrated by a 14C-amino
      acid uptake assay, but does not affect cell viability. Neither sulforhodamine B
      nor lissamine green B inhibit viral replication or recovery in vivo.

PMID- 7510273
TI  - Expression of mucin peptide and blood group ABH- and Lewis-related carbohydrate
      antigens in normal human conjunctiva.
AB  - PURPOSE: The immunohistochemical characterization of mucin peptide antigens and
      identification of blood group ABH- and Lewis-related carbohydrate antigens
      expressed in epithelium of normal human conjunctiva. METHODS: Immunoperoxidase
      characterization of conjunctival glycoproteins was performed using antibodies
      against peptide and saccharide moieties of gastrointestinal mucins on
      conjunctival biopsy specimens from 89 healthy individuals of known ABO and Lewis
      red cell phenotypes. RESULTS: Ocular mucins had epitopes in common with the
      peptidic core of gastric mucin (M1 epitopes), but also contained sialylated
      saccharide chains like those of intestinal mucins. Anti-M1 gastric mucins, anti
      type 1 precursor, and anti-T antibodies strongly stained the cytoplasm of goblet
      cells. Anti-Lea, anti-NeuAc-Lea, and anti-Leb antibodies stained both epithelial
      and goblet cells of Lewis-positive individuals only. Anti-H type 1, anti-H type
      2, anti-A, and anti-B stained epithelial cells of ABH secretors. In addition, A
      like epitopes independent of secretor phenotype were found in epithelial and
      goblet cells of all donors. CONCLUSIONS: The conjunctival mucins cross-react with
      antibodies specific for digestive mucins and for blood group-related carbohydrate
      epitopes. The distributions of Lewis and secretor phenotypes in conjunctiva are:
      19% Lewis-positive nonsecretors, 71% Lewis-positive secretors, and 10% Lewis
      negative secretors. Lea and Leb antigens are present on epithelial cells of Lewis
      positive nonsecretors and Lewis-positive secretors, respectively, as expected for
      antigens under control of Lewis and secretor genes. The secretor alpha-2
      fucosyltransferase is not expressed on goblet cells, as described for the goblet
      cells of the distal rectal colonic mucosae. ABH antigens synthesized by the
      products of A1, A2, B, and Se genes and modulated by the presence of the product
      of the Lewis gene are found in epithelial cells. In addition, A-related epitopes
      independent of the A1-A2 subtype, secretor, and Lewis phenotypes also are present
      in both epithelial and goblet cells.

PMID- 7510272
TI  - Major retinal cell components recognized by onchocerciasis sera are associated
      with the cell surface and nucleoli.
AB  - PURPOSE: Cellular localization of the components recognized by onchocerciasis
      autoantibodies has not been investigated in any detail in cultured retinal cells.
      This study sought to examine, in cultured retinal cells, the subcellular
      localization of major components that cross-react with onchocerciasis sera.
      METHODS: Immunofluorescence confocal laser scanning microscopy and Western blot
      analysis were carried out on adult pig retinal cells. RESULTS: The onchocerciasis
      sera contain antibodies cross-reacting strongly with components of the surface
      and nucleoli in both the cultured retinal pigment epithelial and neural retinal
      cells. These epitopes are not recognized by the control sera obtained from
      noninfected individuals residing in an onchocerciasis hyperendemic area, and from
      those with or without ocular disease who have never been in any of the
      onchocerciasis hyperendemic countries. Double-labeling immunofluorescence
      microscopy does not detect any colocalization of a putative onchocerciasis
      autoantigen, calreticulin, and those cellular components recognized by
      onchocerciasis sera in either cell type. Furthermore, none of the onchocerciasis
      sera tested recognized recombinant calreticulin by Western blot analysis.
      CONCLUSIONS: Major epitopes for onchocerciasis anti-retinal autoantibodies are
      associated with the surface and nucleolus components of retinal cells.
      Interaction of the onchocerciasis antibodies with the retinal cell surface
      molecules may play an important role in the development of ocular diseases
      initiated by the damage of retinal cells. Furthermore, the finding that the
      cellular components recognized by onchocerciasis sera do not colocalize with
      calreticulin, taken together with the observation of lack of recognition of
      recombinant calreticulin by these sera on Western blots, suggests that
      calreticulin is not a major onchocerciasis autoantigen.

PMID- 7510274
TI  - Insulin-like growth factor-related genes, receptors, and binding proteins in
      cultured human retinal pigment epithelial cells.
AB  - PURPOSE: It was determined in cultured human retinal pigment epithelial (HRPE)
      cells whether there is gene expression for insulin, insulin-like growth factors
      (IGFs), insulin and IGF receptors, and IGF-binding proteins (IGFBPs); if these
      peptides are secreted by the HRPE cells, and whether they have mitogenic effects
      on these cells; and if IGF-related peptides bind to HRPE cells. METHODS: Reverse
      transcriptase-polymerase chain reaction (RT-PCR), nucleotide sequencing, and
      Southern blot analyses were done to identify gene expression. The presence of
      IGFs in the tissue culture medium was detected by radioimmunoassay. For
      determination of mitogenic effects and receptor binding characterization, [3H]
      thymidine incorporation and radioreceptor binding measurements were performed.
      RESULTS: The genes for IGF-I and IGF-II, IGFBP-2, insulin receptor, and type I
      and II IGF receptors were detected. In the tissue culture supernatant, there was
      immunoreactivity for IGF-I and IGF-II. Insulin, IGF-I, and IGF-II stimulated DNA
      synthesis with EC50s of 3, 10, and 30 to 100 nM, respectively. Scatchard analyses
      of [125I]-IGF-I binding and [125I]-insulin binding to the cells showed that the
      cells have relatively abundant insulin and IGF-I binding sites. CONCLUSIONS: HRPE
      cells express genes for IGF-I and IGF-II, and conditioned medium from these cells
      is immunoreactive to their protein products. The cells express genes for insulin
      receptor, type I and II IGF receptors, and IGFBP-2. IGF-I, IGF-II, and insulin
      are all mitogenic, possibly as a result of their interactions with either the
      insulin or type I IGF receptor. The cells bind insulin and IGF-I with high
      affinity. These results suggest that IGF-I and IGF-II production by HRPE cells
      may be essential for autocrine/paracrine-mediated regulation of proliferation.
      The presence of insulin receptor suggests that insulin has a role in the
      regulation of HRPE function.

PMID- 7510275
TI  - Multidisciplinary treatment of head and neck cancer using BCG, OK-432, and GE-132
      as biologic response modifiers.
AB  - Since 1979, we have performed multidisciplinary treatment using intensive
      immunotherapy with biologic response modifiers (BRM) in combination with surgical
      treatment of oral cancer. Chemotherapy and radiotherapy were also included as
      part of the therapy. A historic control study was performed. Adjuvant therapy was
      administered by standardized methods, and the distribution of patients at various
      stages was similar between groups. The immunotherapy group showed a shorter
      treatment period, lower rates of recurrence, metastases, and side effects,
      greater histologic effects at the end of the first treatment, and a higher
      survival rate than the nonimmunotherapy group. Immunologically, immunotherapy
      tended to promote positive immune reactions and inhibit negative immune
      reactions.

PMID- 7510276
TI  - Laryngeal preservation by induction chemotherapy plus radiotherapy in locally
      advanced head and neck cancer: the M. D. Anderson Cancer Center experience.
AB  - Standard treatment of locally advanced laryngeal, hypopharyngeal, and some
      oropharyngeal cancers includes total laryngectomy. In an attempt to preserve the
      larynx through induction chemotherapy, we conducted two consecutive phase II
      studies. From March 1986 to February 1991, 64 patients with advanced untreated
      but resectable head and neck cancer who would require total laryngectomy were
      enrolled on one of two cisplatin-based induction regimens: cisplatin-bleomycin-5
      fluorouracil (PBF) in 31 patients and cisplatin-5-fluorouracil (PF) in 33; all
      received definitive radiotherapy. Surgery was reserved for patients who achieved
      less than a partial response to chemotherapy and patients with residual or
      recurrent disease after sequential chemotherapy plus radiotherapy. Overall
      complete plus partial response rates to both cisplatin-based regimens were
      comparable. The combined PF and PBF overall response rates were 75% for laryngeal
      cancer, 78% for hypopharyngeal cancer, and 75% for oropharyngeal cancer. Complete
      response rates after radiotherapy were 88%, 83%, and 50%, respectively.
      Neutropenia (< 1,000 cells/mm3) was the most common hematologic toxic effect: it
      occurred in 44% of patients who received PF and 16% of those who received PBF.
      Grade > or = 3 mucositis occurred in 50% of patients who received PF and 4% who
      received PBF. The data suggest that laryngeal preservation was feasible in all
      three primary-site subgroups. With follow-up of 15+ to 54+ months, 44% of
      patients with laryngeal cancer, 28% with hypopharyngeal cancer, and 22% with
      oropharyngeal cancer are alive with laryngeal preservation. The overall 2-year
      survival rates for patients with cancer of the larynx, hypopharynx, and
      oropharynx were 71%, 46%, and 38%, respectively.

PMID- 7510278
TI  - Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to
      zero gravity.
AB  - This study ascertained the effects of 9 days of zero gravity on the relative
      (percentage of total) and calculated absolute (mg/muscle) content of isomyosin
      expressed in both antigravity and locomotor skeletal muscle of ground control
      (CON) and flight-exposed (FL) rats. Results showed that although there were no
      differences in body weight between FL and CON animals, a significant reduction in
      muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the
      vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and
      myofibril protein content were not different between the muscle regions examined
      in the FL and CON groups. In the VI, there were trends for reductions in the
      relative content of type I and IIa myosin heavy chains (MHCs) that were offset by
      increases in the relative content of both type IIb and possibly type IIx MHC
      protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The
      same pattern held true for the red region of the VL as examined at both the
      protein and mRNA level (P < 0.05). When the atrophy process was examined, there
      were net reductions in the absolute content of both type I and IIa MHCs that were
      offset by calculated increases in type IIb MHC in both VI and red VL.
      Collectively, these findings suggest that there are both absolute and relative
      changes occurring in MHC expression in the "red" regions of antigravity skeletal
      muscle during exposure to zero gravity that could affect muscle function.

PMID- 7510277
TI  - Protective role for neuropeptides in acute pulmonary response to acrolein in
      guinea pigs.
AB  - To determine the potential role of neuropeptides in acrolein-induced airway
      responses, capsaicin-treated guinea pigs were exposed to acrolein aerosol in a
      regimen causing increased airway sensitivity to substance P. Acrolein exposure
      resulted in 100% mortality after capsaicin pretreatment compared with only 14%
      mortality in guinea pigs not pretreated with capsaicin. Acrolein exposure by
      itself caused marked pulmonary inflammation and large airway epithelial necrosis
      and denudation. Pretreatment with capsaicin exacerbated these responses
      throughout the lung. Intravenous acrolein caused an acute dose-related
      bronchoconstriction in naive guinea pigs that was diminished by capsaicin
      treatment and potentiated by thiorphan pretreatment, which suggests that arolein
      exposure causes an acute release of capsaicin-sensitive C-fiber neuropeptides. To
      determine whether acrolein-induced C-fiber release altered neuronal viability,
      either rhodamine or Fast Blue dye was instilled intratracheally into vehicle- or
      acrolein-exposed guinea pigs. Acrolein exposure did not reduce the neuronal
      uptake or retrograde transport of these dyes, as indicated by the number of
      fluorescent cell bodies in the nodose ganglia. To determine the functional state
      of airway neurons, the dose response to intravenous capsaicin was measured in
      vehicle-exposed and acrolein-exposed guinea pigs; no differences were observed.
      Thus, acrolein appears to activate airway C-fibers, which release neuropeptides
      that are protective against this insult, with no suggestion of an accompanying
      reduction in C-fiber function.

PMID- 7510280
TI  - Capsaicin pretreatment attenuates monocrotaline-induced ventilatory dysfunction
      and pulmonary hypertension.
AB  - In view of bronchoconstrictor and proliferative effects of tachykinins (TKs;
      mainly substance P and neurokinin A), as well as increased TK release during
      tissue injury, we hypothesized that monocrotaline (MCT)-induced ventilatory
      dysfunction and pulmonary hypertension may be mediated via TKs. In phase 1 of the
      study (n = 19 rats), we tested and found that elevated lung substance P level and
      suppressed neutral endopeptidase activity occurred 1-2 wk post-MCT (60 mg/kg sc).
      Both phase 2 (n = 32) and phase 3 (n = 32) young Sprague-Dawley rats were divided
      into five groups: control, sham, capsaicin, MCT, and capsaicin + MCT. Rats in the
      control group received no treatment. Each sham rat received the vehicles. Chronic
      capsaicin treatment was used to deplete neuropeptides. Each MCT rat received a
      single injection of MCT 1 wk (phase 2) or 3 wk (phase 3) before the functional
      study. Each capsaicin + MCT rat received the MCT administration 3 days after the
      completion of capsaicin pretreatment. In the MCT group, there were significant
      decreases in dynamic compliance, quasi-static compliance, and the maximal
      expiratory flow rate at 50% total lung capacity in phase 2, which was accompanied
      by significant increases in pulmonary arterial pressure, the weight ratio of
      right ventricle/(left ventricle + septum), and the arterial medial wall thickness
      in phase 3. In the capsaicin + MCT group, however, all the above MCT-induced
      changes were significantly attenuated or abolished. All values from the sham and
      capsaicin groups were not significantly different from those of the control
      group. These data demonstrate that MCT induces pneumotoxicity, accompanied by
      elevated levels of substance P in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510279
TI  - Pulmonary microvascular injury after intestinal ischemia-reperfusion: role of P
      selectin.
AB  - The objective of this study was to determine whether pulmonary endothelial
      expression of the adhesive glycoprotein P-selectin contributes to the lung injury
      and leukostasis observed after intestinal ischemia-reperfusion (I/R). The
      pulmonary capillary filtration coefficient and lung myeloperoxidase activity were
      determined in rat lungs isolated after 120 min of superior mesenteric artery
      occlusion and 90 min of reperfusion. Intestinal I/R resulted in a marked increase
      in the pulmonary capillary filtration coefficient compared with control and sham
      operated rats. The increase in pulmonary microvascular permeability elicited by
      intestinal I/R was effectively prevented by pretreatment with a P-selectin
      monoclonal antibody (MAb; MAb PB1.3) but was unaffected by a control MAb. The
      intestinal I/R-induced increase in pulmonary microvascular permeability was
      accompanied by a dramatic sequestration of granulocytes in the lung compared with
      control and sham-operated rats; however, neither the P-selectin nor the control
      MAbs affected this event. These results indicate that P-selectin contributes to
      the pulmonary microvascular dysfunction observed after intestinal I/R. The
      inhibition of intestinal I/R-induced lung injury by immunoneutralization of P
      selectin appears to be unrelated to the accompanying lung leukosequestration.

PMID- 7510281
TI  - Acid-activated insulin-like growth factor-binding protein-3 proteolysis in normal
      and transformed cells. Role of cathepsin D.
AB  - Insulin-like growth factor-binding protein-3 (IG-FBP-3) is an important member of
      a family of proteins which binds IGF peptides and modulates their biological
      actions. In this study, we describe an acid-activated IGFBP-3 protease in media
      derived from a variety of human cell lines. Radiolabeled IGFBP-3 remained intact
      during incubation (pH 5.5-8) in media conditioned by normal and transformed human
      fibroblasts, MG-63 osteoblastic cells, and breast cancer cell lines MCF-7 and
      Hs578T. However, acidification of the conditioned medium samples (pH < 5.5)
      resulted in 125I-IGFBP-3 hydrolysis and the appearance of specific radiolabeled
      fragments. No proteolysis of 125I-IGFBP-3 occurred during incubation in
      unconditioned medium at neutral or acid pH. Estrogen treatment of estrogen
      receptor-positive MCF-7 cells enhanced acid-activatable IGFBP-3 proteolysis in
      the cell-conditioned medium but had no effect on proteolytic activity in estrogen
      receptor-negative Hs578T cells. The cell-derived IGFBP-3 protease was identified
      as the aspartic proteinase cathepsin D, based on acidic pH optimum, inhibition by
      pepstatin, distinctive proteolytic fragment pattern, and immunoreactivity with
      cathepsin D antisera. Furthermore, immuno-depletion of cathepsin D effectively
      attenuated acid-activated IGFBP-3 proteolysis. These data suggest a role for
      cathepsin D in the regulation of cellular IGF action by virtue of its potential
      to alter the structure/function of IGFBP-3.

PMID- 7510282
TI  - Relationships between rhodamine 123 transport, cell volume, and ion-channel
      function of P-glycoprotein.
AB  - The P-glycoprotein (Pgp), a plasma membrane protein overexpressed in multidrug
      resistant tumor cells, is thought to be both an ATPase that actively exports
      cytotoxic drugs and a Cl- channel activated by cell swelling. The partial
      reversal of multidrug resistance by Cl- transport blockers suggests a possible
      role for Cl- in Pgp-mediated drug transport. We used multidrug-resistant Chinese
      hamster fibroblasts and human breast cancer cells expressing Pgp to study the
      roles of Cl- (and also Na+ and HCO3-/CO2) on Pgp-mediated efflux of the
      fluorescent dye rhodamine 123 (R123). In Pgp-expressing Chinese hamster
      fibroblasts, exposed to isosmotic solutions, the unidirectional efflux of R123
      was not measurably changed by a approximately 60-min removal of Cl- (or by
      exposure to Na(+)-free, or nominally HCO3-/CO2-free medium); short term (2-3 min)
      ion substitutions were also ineffective. In human breast cancer cells transfected
      with human mdr1 cDNA, hyposmotic solutions activated a Cl- current but had no
      effect on the Pgp-mediated unidirectional efflux of R123. Additionally, in human
      breast cancer cells, the intracellular presence of R123 did not prevent
      activation of the Cl- current by hyposmotic solution. The lack of detectable
      effect of removal of Cl-, Na+, or HCO3- on Pgp-mediated R123 transport rules out
      direct coupling between substrate transport and transport of either of these ions
      by Pgp. The persistence of Pgp-mediated R123 efflux in osmotically swollen cells
      indicates that activation of the Pgp-associated Cl- current does not hinder the
      Pgp pump function. The lack of effect of R123 on swelling-activated Cl- current
      denotes that Pgp-mediated transport of organic substrates and Pgp-associated Cl-
      currents can occur at the same time in a single cell. These results underscore
      the dissociation between Pgp-mediated active drug transport and electrodiffusive
      Cl- transport.

PMID- 7510284
TI  - Selective cloning of cDNA for secretory proteins of early embryos. Identification
      of a transiently expressed kunitz domain protein from preimplantation sheep
      trophoblast.
AB  - The preimplantation ovine conceptus transiently secretes several proteins,
      including a type I interferon (IFN-tau), that are likely involved in
      establishment of pregnancy. A method has been developed to identify proteins
      produced simultaneously with IFN-tau. An antiserum against total ovine conceptus
      secretory proteins, from which IFN-tau and proteins common to maternal uterine
      tract secretions had first been removed, was used to immunoscreen cDNA libraries
      created from mRNA of days 13 and 15 ovine conceptuses. This approach has allowed
      several unique cDNA to be identified, including one particularly abundant
      transcript for a novel member of the Kunitz family of serine protease inhibitors.
      This cDNA encodes a 265-amino acid protein with a 20-amino acid signal sequence.
      A 64-amino acid Kunitz domain occupies the carboxyl terminus. It is preceded by
      two similar repeats of 84 residues that bear no obvious similarity to any
      sequences present in the protein data banks. The protein present in conceptus
      secretions (M(r) of approximately 14,000) represents only the carboxyl terminus
      of the molecule. The mRNA for this putative proteinase inhibitor was confined to
      trophectoderm and was highly expressed for only a few days (approximately 13-18)
      of development. A similar transcript was detected during the days 17-21 period in
      cattle embryos. Despite their high expression, no proteinase-inhibitory activity
      can so far be ascribed to either the ovine or bovine proteins. The P1 residue, an
      asparagine, is not represented in any other known Kunitz inhibitors.

PMID- 7510283
TI  - Chemo-enzymic backbone engineering of proteins. Site-specific incorporation of
      synthetic peptides that mimic the 64-74 disulfide loop of granulocyte colony
      stimulating factor.
AB  - We present the concept of chemo-enzymic backbone engineering of proteins.
      Recombinant DNA techniques are used to produce appropriate proteins that are
      enzymically fragmented to give the starting materials. These fragments are
      modified specifically at their chain termini either enzymically (coupling of a
      hydrazide to the C terminus) or chemically (periodate oxidation of N-terminal
      serine to a glyoxylyl function). The modified fragments, which need no side
      protection whatever, are mixed together and religate themselves spontaneously
      under mild conditions. The hydrazone bond thus formed can be reduced if desired,
      which stabilizes the linkage and enhances the flexibility of the local
      conformation. In this way biologically or chemically derived structures can be
      incorporated into the protein, and the choice of the chemical ones is free of all
      of the constraints of the genetic code. We believe that this combined approach
      gives access to constructions that could not be derived by either recombinant or
      chemical methods alone. We illustrate the particularity of this concept by the
      engineered modifications of the 64-74 disulfide loop region of human granulocyte
      colony-stimulating factor. Analogs constructed include one which, in spite of
      having a nonpeptide link in its backbone, has full biological activity.

PMID- 7510286
TI  - Differentiation-specific expression of human keratin 1 is mediated by a composite
      AP-1/steroid hormone element.
AB  - Human keratin 1 (HK1) expression is associated with the loss of mitotic activity
      in epidermal keratinocytes and restricted to an intermediate stage of terminal
      differentiation. Recently, the control elements that mediate this differentiation
      specific expression were identified (Huff, C. A., Yuspa, S. H., and Rosenthal, D.
      (1993) J. Biol. Chem. 268, 377-384). We now report the characterization of one of
      these elements. Footprint analysis on a 249-base pair fragment containing the
      calcium responsive element (CaRE) revealed two adjacent protected regions. The 5'
      most footprint contains an AP-1 consensus sequence while the 3' footprint encodes
      two inverted repeats of the canonical hormone response recognition sequence.
      Deletion of the AP-1-protected region abolished the calcium response in a
      reporter construct. Calcium activation of the reporter construct containing the
      intact CaRE was unaffected by the addition of thyroid hormone or estrogen.
      However, vitamin D3 was able to suppress calcium induction by the CaRE, and this
      suppression could be abrogated by the coaddition of retinoic acid. These studies
      show that AP-1 factors bind to the 5' element to mediate the calcium response
      while members of the steroid hormone receptor superfamily interact with the 3'
      element to modulate the calcium response.

PMID- 7510287
TI  - Clustering and co-transcription of the Bacillus subtilis genes encoding the
      aminoacyl-tRNA synthetases specific for glutamate and for cysteine and the first
      enzyme for cysteine biosynthesis.
AB  - The Bacillus subtilis cysE and cysS genes encoding, respectively, the serine
      acetyltransferase and the cysteinyl-tRNA synthetase were found downstream from
      the gltX gene encoding the glutamyl-tRNA synthetase. This gene organization is
      also conserved in Bacillus stearothermophilus where the cysE and cysS genes show
      high amino acid identity with those of B. subtilis. In both organisms the coding
      sequences of cysE and cysS overlap, suggesting a translational coupling. B.
      subtilis cysE and cysS were expressed in Escherichia coli using the inducible trc
      promoter; they functionally complement mutants of E. coli affected in those
      genes. Overproduction of B. subtilis CysRS in E. coli has a toxic effect on cell
      growth. Disruption of gltX and cysS by Campbell-type insertion is lethal for the
      cell, indicating that these genes code for an essential and unique function in B.
      subtilis. S1 mapping analysis shows that the transcription of gltX is under the
      control of a sigma A promoter located 43 base pairs upstream of the initiation
      codon. A T-box sequence and a rho-independent terminator known to regulate
      expression of other aminoacyl-tRNA synthetase genes and of some amino acid
      biosynthetic operons in Bacillus sp., were found between gltX and cysE. No sigma
      A promoter was detected upstream of cysE, which is consistent with the lethality
      of a Campbell-type insertion using a plasmid that interrupts transcription coming
      from the gltX promoter, and suggests that gltX, cysE, and cysS constitute an
      operon. This is the first case where genes implicated in the biosynthesis of an
      amino acid and its cognate aminoacyl-tRNA synthetase are shown to be co
      transcribed.

PMID- 7510289
TI  - Expression of meprin subunit precursors. Membrane anchoring through the beta
      subunit and mechanism of zymogen activation.
AB  - The biosynthesis of the membrane-bound metalloendopeptidase meprin was studied
      after the introduction of cDNAs encoding the rat meprin alpha and beta subunits
      into human 293 cells. When expressed individually the meprin alpha subunit was
      found to be primarily secreted into the culture medium, while the beta subunit
      was determined to be an integral membrane protein. Coexpression of the alpha and
      beta subunits results in the localization of both subunits to the plasma
      membrane. In this case the alpha subunit is specifically released from the cell
      surface by dithiothreitol, indicating the alpha subunit is associated with the
      membrane via disulfide bond(s) to the beta subunit. Meprin expressed in 293 cells
      is similar to the rat kidney enzyme in that it forms disulfide-linked dimers and
      has a similar pattern of glycosylation. However, the expressed protein displayed
      no detectable peptidase activity against four meprin substrates. Processing of
      the alpha subunit was followed after the introduction of sequences coding for the
      human c-myc peptide epitope EQKLISEEDL into its cDNA in the region of its
      prosequence and at the COOH terminus. Detection of the resulting proteins using a
      monoclonal antibody specific for the c-myc epitope indicates the alpha subunit is
      processed at its COOH terminus but retains the prosequence which is absent from
      the enzyme purified from rat kidney. Limited trypsin digestion of meprin
      precursors expressed in 293 cells results in both the activation of the enzyme
      and the removal of the prosequence. This result supports the hypothesis of Bode
      et al. (Bode W., Gomis-Ruth, F. X., Huber, R., Zwilling, R., and Stocker, W.
      (1992) Nature 358, 164-167) that meprin and other astacin family proteases
      require removal of NH2-terminal prosequences at the junction of the astacin
      protease domain for zymogen activation. Trypsin-activated meprin was assayed with
      the protein substrate azocasein and three synthetic peptide substrates. The
      membrane-bound beta subunit was found to be more active than the secreted alpha
      subunit against azocasein but much less active toward the synthetic peptide
      substrates.

PMID- 7510288
TI  - Localization of Saccharomyces cerevisiae ribosomal protein L16 on the surface of
      60 S ribosomal subunits by immunoelectron microscopy.
AB  - Antibodies raised against a trpE-L16 fusion protein expressed in Escherichia coli
      were used to examine immunological relatedness between Saccharomyces cerevisiae
      ribosomal protein L16 and ribosomal proteins from eubacteria, halobacteria,
      methanogens, eocytes, and other eukaryotes. Homologues of L16 also were
      identified by searches of sequence data bases. Among the bacterial proteins that
      are immunologically related and similar in sequence to L16 are ribosomal proteins
      that bind 5 S rRNA. L16 protein fused near its carboxyl terminus to E. coli beta
      galactosidase could assemble into functional yeast 60 S ribosomal subunits. The
      RPL16A-lacZ gene fusion partially complemented the slow growth or lethality of
      mutants containing null alleles of one or both RPL16 genes, respectively. L16
      beta-galactosidase fusion protein cosedimented with ribosomes and polyribosomes,
      and remained associated with high salt-washed ribosomes. Monoclonal antibodies
      against beta-galactosidase were used to map the location of L16-beta
      galactosidase on the surface of the 60 S subunit by immunoelectron microscopy.
      L16 was localized near the top surface of the central protuberance, where the 60
      S subunit potentially contacts the 40 S subunit. This is similar to the location
      of the bacterial homologues of L16 in 50 S ribosomal subunits.

PMID- 7510290
TI  - Functional characterization of cystic fibrosis transmembrane conductance
      regulator (CFTR) in apical membranes purified from bovine tracheal epithelium.
AB  - Inside-out apical membrane vesicles were isolated from bovine tracheal
      epithelium. They were enriched 13- and 18-fold in two apical membrane markers,
      alkaline phosphatase and gamma-glutamyltransferase, respectively, and presented a
      low level of contamination by basolateral and intracellular membranes. These
      apical membrane vesicles of homogeneous inside-out orientation were used to
      measure 36Cl- influx. The 36Cl- influx was found to be (i) voltage-insensitive
      (ii) diphenylcarboxylic acid-insensitive, and (iii) from 55 to 100% activated by
      cAMP-dependent protein kinase according to initial rates and accumulation
      capacities. This rapid and ATP-dependent activation was associated with
      phosphorylation of a 170-180-kDa protein but was not observed with a
      nonhydrolyzable nucleotide like adenosine 5'-O-(3-thiotriphosphate).
      Immunodetection experiments showed that the mature form of bovine cystic fibrosis
      transmembrane conductance regulator (CFTR) was only present in the apical
      membranes. As compared with the previously described characteristics of CFTR, the
      36Cl- uptakes detected here are the in vitro manifestation of the functional form
      of bovine CFTR located at the apical level in these tracheal epithelial cells.
      Inside-out apical membrane vesicles, with freely accessible cytoplasmic sides and
      functional CFTR, offer a new model system to study CFTR.

PMID- 7510291
TI  - Delivery of growth factor to wounds using a genetically engineered biological
      bandage.
AB  - Increasing the rate of wound healing of acute wounds and promoting the closure of
      chronic ulcers is an important goal in wound therapy. Growth factors have been
      shown to facilitate this process; however, the systems described for growth
      factor delivery are not ideal. In the present report we demonstrate the
      feasibility of a new method of delivering growth factors to the wound site using
      a genetically engineered biological bandage. The bandage consists of
      keratinocytes (SCC-13 cells) that are engineered by gene transfer to produce high
      levels of bovine growth hormone (bGH). bGH was selected for these studies because
      it can be easily distinguished from rat and human growth hormone in wound fluids
      and culture medium. The bGH-producing cells are contained and maintained in serum
      free medium inside an envelope composed of a low protein binding, 0.2 micron pore
      size, polysulfone membrane. The genetically engineered cells cannot escape from
      the bandage, but the bGH is freely released into the surrounding culture medium.
      When placed onto a full-thickness, surgically generated wound on rats, the cells
      within the bandage continue to produce and release bGH into the wound for at
      least 3 days. This system is a safe and reliable way of providing real-time
      delivery of any desired biomolecule into the wound site.

PMID- 7510285
TI  - Membrane topology of the L6 antigen and identification of the protein epitope
      recognized by the L6 monoclonal antibody.
AB  - The murine monoclonal antibody (mAb) L6 recognizes an integral membrane
      glycoprotein that is highly expressed on lung, breast, colon, and ovarian
      carcinomas and is referred to as the L6 antigen. This antigen is an attractive
      target for therapeutic intervention due to its high level expression on malignant
      cells. We have previously reported the isolation of a cDNA encoding the human L6
      antigen (H-L6). Here, we report the isolation of a cDNA clone encoding the murine
      L6 antigen (M-L6). This cDNA contains one long open reading frame, which encodes
      a 220-amino acid polypeptide that is 78% homologous to H-L6. This protein
      contains short NH2- and COOH-terminal hydrophilic domains and four hydrophobic
      regions, each long enough to span the plasma membrane. Each of these hydrophobic
      domains is separated by a hydrophilic domain, the longest of which contains one
      possible N-linked glycosylation site and is located between the third and fourth
      hydrophobic domains. We have previously demonstrated that the murine L6 mAb
      recognizes a protein epitope expressed on human tumor-derived cell lines. Now,
      using chimeric cDNA constructs encoding human-murine L6 antigen hybrids in
      conjunction with monoclonal antibody binding experiments, we show that the 42
      residue hydrophilic domain of the L6 antigen, located between the third and
      fourth hydrophobic domains, is outside the cell and that residues in the NH2
      terminal region of this domain are critical for the binding of the murine L6 mAb
      to H-L6.

PMID- 7510292
TI  - Combinations of interferon with platinum complexes: synergistic and antagonistic
      effects on growth inhibition of MCF-7 and MDA-MB231 breast cancer cells.
AB  - The growth-inhibitory effects of combining interferons (IFN) with platinum(II)
      complexes were tested with the aim of comparing these in cultures of estrogen
      receptor(ER)-negative MDA-MB231 and ER-positive MCF-7 breast cancer cell lines.
      Another aim was to test whether IFN as a biological response modifier could
      enhance the effect of the Pt complexes in vitro in an attempt to find an
      explanation for their more potent antitumor effects in in vivo models. Here it is
      shown that in both cell lines the combinations of different IFN with all three Pt
      complexes generally resulted in additive growth inhibition, as calculated by the
      product of the fraction of surviving cells obtained with each compound alone.
      Moreover, in MCF-7 cells natural IFN beta (nIFN beta) combined with aqua[meso-1,2
      bis-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] sulfatoplatinum(II) (meso-6
      Pt) resulted in synergistic inhibition. This synergy could be attributed to the
      estrogenic property of meso-6-Pt, since the ligand and estradiol also enhanced
      the inhibitory effect of nIFN beta. In contrast, the combination of recombinant
      IFN gamma and meso-6-Pt was antagonistic in MDA-MB231 cells. These results show
      that, in spite of the similar responses of the ER-negative and ER-positive cells
      to each compound alone, these cells show unexpected differences in their
      sensitivity to combinations of IFN and the new Pt complex meso-6-Pt.

PMID- 7510293
TI  - Up-regulation of aFGF expression in quiescent cells is related to cell survival.
AB  - Exogenously administrated acidic FGF modulates the proliferation of several cell
      types, controls cell differentiation, and promotes cell survival. Most cells that
      are sensitive to exogenous aFGF are also capable of expressing it at very low
      levels. Thus in order to establish the role of endogenous aFGF as a mitogenic,
      differentiation, or survival factor, we studied the regulation of aFGF expression
      by evaluating the level of mRNA by PCR amplification and the concentration of
      protein by Enzyme Immuno Assay (EIA). In the lens, the amount of aFGF transcripts
      in nondividing cells of the central epithelium and in the differentiated fiber
      cells located at the periphery of the lens is similar, suggesting that endogenous
      aFGF is not involved with lens differentiation. In cultures, depending on the
      growth conditions, the endogenous aFGF expressed by Bovine Epithelial Lens (BEL)
      cells is subject to modulation. Cells arrested either by contact inhibition or by
      serum deprivation express more aFGF transcripts and protein than in exponentially
      growing cells, implying that endogenous aFGF has no mitogenic role under these
      conditions. In serum-deprived cells, the addition of specific aFGF antisense
      primers inhibits endogenous aFGF expression and leads to the death of these
      cells. These results associated with the higher expression of aFGF in nondividing
      BEL cells, suggesting that, contrary to exogenous aFGF, endogenous aFGF is not a
      mitogenic factor but a survival factor.

PMID- 7510294
TI  - Stimulatory effect of a phorbol ester on expression of insulin-like growth factor
      (IGF) binding protein-2 and level of IGF-I receptors in mouse osteoblastic MC3T3
      E1 cells.
AB  - We examined the relationship between signal transduction and the expression of
      insulin-like growth factor I (IGF-I), IGF-I receptor level, and IGF binding
      proteins (IGFBPs) in murine clonal osteoblastic MC3T3-E1 cells. 12-O
      Tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C,
      decreased the secretion of immunoreactive IGF-I into the medium, whereas
      dibutyryl cAMP (Bt2cAMP) augmented the secretion. In contrast, TPA increased the
      level of type I IGF receptor on the cells. Furthermore, MC3T3-E1 cells produced
      and secreted at least three different IGFBPs with molecular masses of 24, 30, and
      34 kDa, and the 24-kDa IGFBP was predominant under normal conditions. However,
      TPA specifically increased the secretion of the 34-kDa IGFBP. The N-terminal
      amino acid sequence of the purified 34-kDa IGFBP was nearly identical with that
      of rat IGFBP-2. Furthermore, the 34-kDa IGFBP was immunoreactive to anti-IGFBP-2
      antiserum. The level of IGFBP-2 mRNA in the cells was increased by TPA,
      indicating that the increase in IGFBP-2 secretion results from the stimulation of
      IGFBP-2 production. In contrast, Bt2cAMP affected neither IGF-I receptor number
      nor the IGFBP secretion. These results indicate that the production of IGF-I and
      the expression of IGF-I receptors and IGFBP-2 are up-regulated by the activation
      of adenylate cyclase and protein kinase C, respectively, in osteoblastic MC3T3-E1
      cells.

PMID- 7510296
TI  - Pinocytic stimulation in Dictyostelium discoideum by gamma-benzene hexachloride.
AB  - Pinocytic activity is greatly stimulated in gamma-BHC (gamma isomer of benzene
      hexachloride) treated, vegetative cells of Dictyostelium discoideum as measured
      by 14C sucrose or FITC-dextran uptake. Transmission electron microscopic studies
      also reveal the presence of a greater number of pinosomal vesicles in the
      pesticide-treated Dictyostelium amoebae. The enhanced pinocytic activity has been
      discussed in relation to lipophilic interactions of gamma-BHC with the
      hydrophobic cell surface and the observed changes in the cytoskeletal proteins of
      the treated cells.

PMID- 7510295
TI  - Regulation of Na+/glucose cotransporter (SGLT1) mRNA in LLC-PK1 cells.
AB  - The porcine kidney epithelial cell line LLC-PK1 expresses a sodium-coupled
      glucose cotransporter (SGLT1) together with other differentiation markers of
      renal proximal tubule such as trehalase and gamma-glutamyltranspeptidase.
      Expression is regulated by cell density and exogenous differentiation inducers
      such as hexamethylene bisacetamide (HMBA). Northern blot and PCR analysis of
      clonal cell populations indicated SGLT1 mRNA was not detectable in subconfluent
      cultures, but 2.2 and 3.9 kb SGLT1 mRNA species appeared after cell confluence,
      accompanying expression of the transport activity. SGLT1 mRNA levels were
      significantly increased after treatment of confluent cultures with HMBA,
      paralleling increases in the transport activity and immunodetectable 75 kD
      cotransporter subunit. SGLT1 mRNA was also increased after treatment of cultures
      with the cyclic AMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine
      (IBMX), an inducer of Na+/glucose cotransport activity. The 3.9 kb SGLT1
      transcript showed the largest increase after either HMBA or IBMX treatment. HMBA
      treatment also resulted in increased mRNA levels of two other differentiation
      markers--trehalase and gamma-glutamyltranspeptidase. By contrast, trehalase and
      gamma-glutamyltranspeptidase mRNA levels were not increased by IBMX. Regulation
      of Na+/glucose symporter expression by either cell density, cyclic AMP elevation,
      or differentiation inducer treatment occurs, at least in part, at the level of
      SGLT1 mRNA and can be dissociated from regulation of other differentiation
      markers.

PMID- 7510297
TI  - Epitope mapping and functional studies with three monoclonal antibodies to the c
      kit receptor tyrosine kinase, YB5.B8, 17F11, and SR-1.
AB  - Three monoclonal antibodies (MAbs) to the human c-kit receptor tyrosine kinase
      (P145c-kit), derived in independent laboratories, have been extensively used in
      studies of c-kit expression and the role of its ligand, steel factor (SLF), in
      hemopoiesis and mast cell differentiation and function. In this study, the
      relationship between the epitopes they identify, and their effects on SLF
      binding, receptor internalization, and signal transduction are compared. Epitope
      mapping studies carried out on the high P145c-kit-expressing cell line HEL-DR
      showed that SR-1 identifies an epitope independent of those bound by YB5.B8 and
      17F11, while the latter two antibodies bound to distinct but interacting
      epitopes. SR-1 potently blocked the binding of SLF to P145c-kit on these cells
      and also on cells of the factor-dependent line MO7e. In contrast, YB5.B8 and
      17F11 had minimal effects on ligand binding. Conversely, SLF partially blocked
      the binding of SR-1 and YB5.B8 to cells, while binding of 17F11 was actually
      enhanced by SLf on some target cells. Preincubation of HEL-DR and MO7e cells with
      MAbs prior to exposure to SLF revealed that 17F11 itself brought about partial
      down-regulation of P145c-kit and did not inhibit SLF-mediated down-regulation. SR
      1 caused minimal down-regulation and inhibited SLF-mediated receptor
      internalization. YB5.B8 had minimal effects on either cell line in this assay. To
      determine whether the antibodies had any agonist activity, they were compared
      with SLF for their ability to bring about receptor phosphorylation in intact MO7e
      cells. All three antibodies induced detectable tyrosine phosphorylation with
      17F11 being the most effective, while YB5.B8 was the least effective. Finally,
      the ability of the antibodies to influence the proliferation of the MO7e cells
      was examined. As expected, SR-1 potently inhibited the proliferative response to
      SLF, while 17F11 weakly inhibited and YB5.B8 had negligible effect. In the
      absence of SLF both 17F11 and YB5.B8 displayed very weak but reproducible agonist
      activity.

PMID- 7510298
TI  - The locomotion, shape and pseudopodial dynamics of unstimulated Dictyostelium
      cells are not random.
AB  - The dynamic periphery of unstimulated, preaggregation, hunger-stage Dictyostelium
      discoideum amoebae was investigated by time-lapse videomicroscopy and digital
      image processing. Circular maps (i.e. of each of 360 radii around the cell
      transformed upon Cartesian coordinates) were constructed around the centroid of
      individual cell images and analysed in time series. This novel technique
      generated spatiotemporal structures of various degrees of order in the maps,
      which resemble classical wave interference patterns. The patterns thus
      demonstrate that cell movement is not random and that cells are intrinsically
      vibrating bodies, transited by self-organized, superpositioned, harmonic modes of
      rotating oscillatory waves (ROWS). These waves appear to depend upon
      spatiotemporal oscillations in the physicochemical reactions associated with
      actin polymerization, and they govern pseudopodial movements, cell shape and
      locomotion generally. ROWS in this case are unrelated to the cyclic-AMP-regulated
      oscillations, which characterize later, aggregative populations of Dictyostelium.
      However, the exposure of aggregation-stage cells to a pulse of the
      chemoattractant cyclic-AMP induces a characteristic sequence of changes in the
      global cellular concentration and spatiotemporal distribution of fibrillar (F
      )actin. This reaction begins with what appears to be a phase resetting of ROWS
      and it may, therefore, underlie the cellular perception of and response to
      chemotactic signals. We also develop here an analytical mathematical description
      of ROWS, and use it to simulate cell movements accurately.

PMID- 7510302
TI  - Orientation of macromolecules in the walls of elongating carrot cells.
AB  - When round cells from a carrot cell suspension culture are diluted into fresh
      medium without auxin, the cells elongate to almost 50 times their original
      diameter within three days. This process of elongation is accompanied by changes
      in both the composition and the orientation of cell wall polymers. We have
      obtained information on the orientation of wall polymers in elongating cells by
      two complementary techniques, one using microscopy and one spectroscopy. Images
      obtained by the fast-freeze, deep-etch, rotary-shadowed replica technique show
      that walls of round carrot cells have no net orientation of cellulose
      microfibrils, and that many thin fibres can be seen cross-linking microfibrils.
      Walls of elongated carrot cells, in contrast, show a marked net orientation of
      microfibrils at right angles to the axis of elongation. Fourier Transform
      Infrared (FTIR) spectra obtained from defined areas of single cell walls show
      that walls of round carrot cells contain more protein, esters and phenolics in a
      given area (10 microns x 10 microns) than walls of elongated carrot cells, that
      contain proportionally more carbohydrate. The orientation of particular
      functional groups, with respect to the direction of elongation of the cell, can
      be determined by inserting a polariser into the path of the infrared beam, before
      it passes through a cell wall sample mounted on the stage of the microscope
      accessory. In the walls of elongated cells, ester bands, amide bands
      characteristic of proteins, and stretching frequencies in the carbohydrate region
      of the spectrum all show a net orientation transverse to the long axis of the
      cells. In the walls of round carrot cells, however, there is no such net
      orientation of polymers. Spectra obtained from 25 microns-thick fresh sections of
      the etiolated stem of a carrot seedling show that different wall components are
      polarised in different tissue types. These techniques have therefore enabled us
      to define differences in both the composition and the architecture of walls of
      elongating cells at the level of a single cell, and to suggest that polymers not
      previously thought to be ordered, such as pectin and protein, are strictly
      oriented in some wall types.

PMID- 7510299
TI  - Rous sarcoma virus-transformed cells develop peculiar adhesive structures along
      the cell periphery.
AB  - Alteration of the cell/substratum adhesive structures of rat fibroblasts (3Y1
      cells) upon transformation by Rous sarcoma virus (RSV) was investigated by
      immunofluorescence microscopy. In serum-containing culture medium, 3Y1 cells
      developed focal adhesions as their main adhesive structures, while BY1 cells
      expressed peculiar close contacts along the cell periphery with the vitronectin
      receptor integrin, in addition to podosomes. These peripheral close contacts are
      referred to as the peripheral adhesions. The peripheral adhesions were observed
      as a darker region than podosomes by interference reflection microscopy. They
      were more easily destroyed by incubating the cells with RGD-containing peptide
      than were the focal adhesions. In contrast to focal adhesions and podosomes,
      actin bundles were not detected within the peripheral adhesions, where pp60v-src
      and tyrosine-phosphorylated proteins accumulated. Expression of the integrin was
      determined by the substratum composition when BY1 cells were cultured in serum
      free culture medium. Under such conditions, BY1 cells expressed the peripheral
      adhesions within 3 hours on adhesion molecule-coated glass. On the other hand, in
      serum-containing medium, they first developed focal adhesions transiently at
      their early stage of adhesion, and then the peripheral adhesions were
      predominantly expressed within 12 hours. Podosomes were formed in a time course
      similar to that of the peripheral adhesions. These findings suggest that the
      peripheral adhesion is a class of stable adhesive structure distinct from the
      focal adhesion or podosome of BY1 cells. Similar close contact-type peripheral
      adhesions with the integrin were also observed in a variety of cultured cells
      such as normal fibroblasts at their logarithmic growth phase, phorbol ester
      treated fibroblasts, and several malignant tumor cells, with poorly organized
      focal adhesions and stress fibers. These findings further suggest that the
      peripheral adhesions may be widely involved in the adhesion of cells that
      inadequately develop stress fibers and focal adhesions.

PMID- 7510301
TI  - Protein kinase C-dependent phosphorylation of a ciliary membrane protein and
      inhibition of ciliary beating.
AB  - The present study examined whether protein kinase C phosphorylated a ciliary
      protein and whether this phosphorylation event was temporally correlated with a
      decrease in ciliary beat frequency. Activation of protein kinase C decreased
      ciliary beat frequency of sheep tracheal epithelium, an effect fully blockable by
      pretreatment of the tissue pieces with H-7, a protein kinase inhibitor. Using
      cilia removed from these epithelial surfaces and incubated in solutions
      containing stimulators of protein kinase C along with [gamma-32P]ATP or [gamma
      35S]ATP, a single protein target of ciliary protein kinase C activity was
      identified. The protein is a polypeptide of molecular mass 37 kDa (p37) as
      estimated by SDS-polyacrylamide gel electrophoresis. Protein kinase C dependency
      of p37 phosphorylation was proven by showing that Calphostin C, a specific
      protein kinase C inhibitor, blocked label incorporation into p37 completely, and
      by demonstrating that purified protein kinase C phosphorylated p37. Inhibitors of
      cAMP-dependent kinase and calcium/calmodulin-dependent kinase did not change the
      phosphorylation of p37 in the presence of protein kinase C activators. p37 was
      recovered in a Triton X-100-extractable fraction of this ciliary preparation,
      suggesting that p37 is membrane associated. This hypothesis was further supported
      by the fact that p37 was present in a pellet representing reconstituted
      membranes. Thin-layer electrophoresis revealed that p37 was phosphorylated on
      serine and tyrosine residues, suggesting that the activation of protein kinase C
      also stimulated tyrosine kinase activity. p37 did not precipitate with annexin I
      or II antibodies. These results show that sheep tracheal cilia contain protein
      kinase C activity and that activated protein kinase C phosphorylates a membrane
      associated ovine ciliary target, an effect temporally related to a protein kinase
      C-mediated decrease in ciliary beat frequency.

PMID- 7510300
TI  - Functional down-regulation of alpha 5 beta 1 integrin in keratinocytes is
      reversible but commitment to terminal differentiation is not.
AB  - Extracellular matrix receptors of the integrin family have a dual role in the
      epidermis, regulating both adhesion and differentiation. Loss of contact with the
      extracellular matrix causes keratinocytes to become committed to terminal
      differentiation, and results in a decrease in the ability of the alpha 5 beta 1
      integrin to bind fibronectin. We have investigated whether the decrease in ligand
      binding ability is reversible and, if so, whether commitment to terminal
      differentiation can also be reversed. Keratinocytes that had been placed in
      suspension for 5 hours to induce commitment were compared with the starting
      population (0 hour cells) in the presence or absence of 8A2, an activating anti
      beta 1 antibody. 8A2 IgG or FAb fragments increased the amount of alpha 5 beta 1
      in cell extracts that bound to fibronectin-Sepharose and in the presence of 8A2
      the amount of bound alpha 5 beta 1 in 0 hour and 5 hour extracts was equal. 8A2
      also restored alpha 5 beta 1 function in adhesion assays of intact 5 hour cells.
      Ca2+, Mg2+ and Mn2+ alone, at concentrations of up to 1 mM, did not increase the
      adhesiveness of 5 hour cells relative to 0 hour cells; however, the effect of 8A2
      on keratinocytes was dependent on Ca2+. Although 8A2 restored alpha 5 beta 1
      ligand-binding ability it did not prevent committed cells from withdrawing from
      the cell cycle and expressing involucrin, a differentiation marker.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7510303
TI  - Immunohistochemical localization of transforming growth factor-beta in human
      implantation sites.
AB  - Transforming growth factor-beta (TGF beta), a protein known to antagonize many of
      the functions of the epidermal growth factor-receptor system, was localized
      immunohistochemically in unruptured ectopic pregnancies (EP) removed by
      salpingectomy (n = 8), uterine decidua from EP (n = 4), and decidua and
      trophoblast from electively terminated first trimester pregnancies (ETP; n = 8).
      Two rabbit polyclonal antisera that recognize both TGF beta 1 and beta 2 were
      used. Immunostaining for TGF beta was identified in all three forms of
      trophoblast, cytotrophoblasts, intermediate trophoblasts, and
      syncytiotrophoblasts, which were differentiated histologically and
      immunohistochemically. Moderate cytoplasmic immunostaining was found in villous
      cytotrophoblasts in both EP and ETP. Nonvillous (anchoring) cytotrophoblasts in
      these same tissues demonstrated moderate immunostaining adjacent to the villous
      and light immunostaining distal to the villous. In intermediate trophoblasts,
      moderate to intense immunostaining was seen in EP and ETP. Syncytiotrophoblasts
      demonstrated moderate cytoplasmic immunostaining in EP and ETP as well as
      moderate to intense staining of plasma membranes and microvilli. Nuclear staining
      was not evident in any form of trophoblast. TGF beta immunostaining was
      demonstrated in both glands and stroma of decidua from both EP and ETP; however,
      staining was more intense in decidua from ETP. With the known presence of TGF
      beta receptors and mRNA in placenta, these results suggest an autocrine/paracrine
      role for TGF beta regulation of endometrial-trophoblast function during human
      implantation.

PMID- 7510304
TI  - Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I,
      insulin-like growth factor binding protein-3, and GH-binding protein, after
      craniospinal irradiation and chemotherapy.
AB  - We studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36
      months in six patients with medulloblastoma who underwent surgical removal of the
      tumor followed by craniospinal irradiation therapy for 6 weeks and then
      chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation
      there was a decline in the peak GH secretory response to acute stimulation with
      arginine/insulin hypoglycemia. Six months after irradiation and during
      chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP
      3), and GH-BP values (respective mean values of 56.1 +/- 9.0 ng/mL, 1.1 +/- 0.2
      microgram/mL, and 7.6 +/- 3.3% of radioactivity as compared to time 0 values:
      13%%o/- 15 ng/mL, 2.2 +/- 0.2 micrograms/mL, and 20.0 +/- 4.0%, P < 0.001),
      although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and
      GH-BP returned to pretreatment ranges by 12-36 months after initiation of the
      study. There was also a decline in body mass index and serum protein values at 6
      months, suggesting suboptimal nutrition during this period. Six months after
      irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and
      an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36
      months. In one patient we observed a high level of IGFBP-3 proteolysis at this
      time. This study demonstrates that before the decrease of GH secretion in
      patients receiving cranial irradiation there is a transient phase of GH
      insensitivity that may be characteristic of the acute therapeutic phase including
      the chemotherapy. This partial insensitivity may explain the early growth
      retardation observed in these patients.

PMID- 7510306
TI  - Insulin receptor ribonucleic acid levels and alternative splicing in human liver,
      muscle, and adipose tissue: tissue specificity and relation to insulin action.
AB  - The absolute levels and alternative splicing of insulin receptor RNA molecules
      were determined in samples from liver, muscle, and adipose tissue from 17
      nondiabetic individuals. Both the absolute levels and alternative splicing varied
      in a tissue-specific manner. In all tissues, a majority of the insulin receptor
      RNA molecules contained exon 11. Liver tissue had a lower percentage of RNA
      molecules without exon 11 (Ex 11-) than muscle and adipose tissue, but the
      absolute number of Ex 11- RNA copies was higher due to higher overall levels of
      insulin receptor RNA. Insulin receptor RNA levels in adipose tissue showed
      significant correlation with obesity, expressed as body mass index (kilograms per
      m2) as well as with in vivo insulin action, as measured by the insulin tolerance
      test. In this study, obesity and insulin action were not correlated with insulin
      receptor RNA expression in liver or muscle. Within individuals, no relation was
      detected between the number of insulin receptor RNA copies in a tissue and the
      number or percent Ex 11- RNA in the same tissue. Also, the absolute levels or Ex
      11- percentages in one tissue could not predict corresponding measurements in the
      other two investigated tissues from the same individual.

PMID- 7510307
TI  - Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP-4 in human
      prostatic hyperplastic tissue: gene expression and its cellular localization.
AB  - It has been previously reported that 1) type I insulin-like growth factor (IGF)
      receptors are present in the human prostatic tissue; 2) IGF-I receptors are
      mainly localized in the epithelial cells; 3) IGF-I is a mitogen for prostatic
      epithelial cells in culture; and 4) IGF-binding proteins (IGFBPs) are released by
      these cells in the conditioned medium. To add information on the mechanism of IGF
      I action in the human prostate, we studied the expression and cellular
      localization of mRNA encoding IGF-I and IGFBP-4 in human prostatic hyperplastic
      (BPH) tissue. Northern analysis of total RNA extracted from BPH tissues with cDNA
      probes containing the entire coding regions for IGF-I and IGFBP-4 documented the
      presence of multiple IGF-I mRNA transcripts with lengths of 7.5, 1.7, 1.3, and
      1.1 kilobases and a single 2.1-kilobase transcript of IGFBP-4 mRNA. In situ
      hybridization with the cDNA probes used for Northern analysis and with cRNA
      probes synthesized from the respective cDNA demonstrated that IGF-I mRNA was only
      localized in the stromal cells, whereas IGFBP-4 mRNA was predominantly expressed
      by epithelial cells. In addition, immunoreactive IGF-I was measured in BPH tissue
      extracts after acidification and reverse phase chromatography. The mean (+/- SD)
      IGF-I content of six BPH tissues was 28.1 +/- 4.0 ng/g tissue. Our results
      suggest that in the human prostate, the locally secreted IGF-I exerts its
      principal biological effects with a paracrine mode of action and demonstrate that
      IGFBP-4 is mainly expressed by IGF-I target cells.

PMID- 7510305
TI  - Changes in insulin-like growth factor (IGF)-binding proteins after IGF-I
      injections in noninsulin-dependent diabetics.
AB  - Insulin-like growth factor-I (IGF-I) exerts insulin-like effects on fuel
      metabolism and suppresses insulin secretion in normal subjects. Unlike insulin,
      circulating IGF-I is bound to high affinity binding proteins (IGFBPs), which
      modulate IGF action. We have previously shown that IGF-I administration increases
      IGFBP-1 and -2 and reduces IGFBP-3 in normal subjects. To determine whether
      similar effects could be demonstrated in an insulin-resistant state, we
      administered recombinant human IGF-I for 4 days by sc injection to six obese type
      II diabetics and determined the effects on fasting concentrations of glucose, C
      peptide, IGF-I, and IGFBPs. The changes that occurred in glucose C-peptide and
      IGFBP levels during oral glucose tolerance testing were also quantified. There
      was no significant decrease in the mean fasting serum glucose or C-peptide level
      despite a 7-fold increase in mean fasting IGF-I concentrations (P < 0.01). As
      expected, during oral glucose tolerance testing, the area under the curve of C
      peptide was suppressed after an injection of IGF-I (P < 0.05), but the area under
      the glucose curve did not change significantly. Mean fasting daily IGFBP-1 and -2
      rose 2-fold (P < 0.05) and 1.9-fold (P < 0.05), respectively, whereas IGFBP-3
      fell by 16% (P < 0.01) after 4 days of injections. IGFBP-1 was suppressed by 32%
      after oral glucose alone, whereas an injection of IGF-I plus oral glucose were
      associated with a more marked fall of 53% (despite suppression of C-peptide). In
      contrast, mean IGFBP-2 concentrations rose by 40% (P < 0.05) after IGF-I and oral
      glucose, but there was no change in response to oral glucose alone. These changes
      in IGFBP-1, -2, and -3 could alter the distribution of IGF-I among the various
      IGFBPs in the circulation. They may also prove to be a marker of metabolic
      responsiveness to IGF-I. In a substrate-sufficient state, e.g. after oral
      glucose, IGFBP-1 and -2 show opposite acute responses to IGF-I, and IGF-I has an
      apparent acute insulin-like effect on IGFBP-1 concentrations that differs from
      its longer term effect.

PMID- 7510308
TI  - Direct PCR enables detection of Mycoplasma pneumoniae in patients with
      respiratory tract infections.
AB  - The sensitivities of three methods of detection of Mycoplasma pneumoniae by a 16S
      rDNA PCR were compared by using a serial dilution of M. pneumoniae. These methods
      consisted of a PCR performed directly on cells after a proteinase K pretreatment
      (direct PCR), a PCR after purification of nucleic acids (DNA-PCR), and a PCR with
      rRNA sequences as the target after reverse transcription. The direct PCR and the
      reverse transcription PCR had a sensitivity of 1.5 CFU (approximately 250
      genomes). By purification, a 10-fold loss of target DNA occurred, as shown by a
      10-fold decrease in sensitivity (15 CFU) of the DNA-PCR. The presence of an
      excess of human background DNA did not influence the sensitivity of either PCR.
      The direct PCR was evaluated on samples from patients with respiratory
      complaints. Direct PCR amplification was possible in 94.9% of the samples, which
      were tested by amplification of a 326-bp fragment of the beta-globin gene, which
      was performed to test for the suitability of amplification. Nucleic acid
      purification was performed on the beta-globin-negative samples, after which only
      2% remained negative. A positive correlation between the direct M. pneumoniae PCR
      and serology, as tested by the microparticle agglutination assay (MAG assay), was
      found in 88.1% of the cases. A positive MAG assay result was found for samples
      from 10 (17%) of the patients; samples from 6 (10.2%) of these patients were also
      positive by PCR. Samples from three patients were found to be positive by the M.
      pneumoniae PCR and negative by the MAG assay. Persistence of M. pneumoniae, as
      detected by PCR was observed in three patients. These results indicate that the
      direct PCR with 16S rDNA could prove to be useful in the detection of M.
      pneumoniae in respiratory tract samples, although more studies are needed to
      evaluate the correlation between clinical symptoms and positive test results.

PMID- 7510310
TI  - Modified CAMP test for biogrouping Vibrio cholerae O1 strains and distinguishing
      them from strains of V. cholerae non-O1.
AB  - A modified CAMP test was used to identify 973 Vibrio cholerae isolates by
      phenotype. Eltor and non-O1 strains were CAMP positive; classical strains were
      CAMP negative. Sausage-shaped zones of hemolysis of eltor strains were easily
      distinguished from narrower bands of non-O1 isolates. For O1 isolates, there was
      100% agreement between the CAMP test and inhibition by polymyxin B.

PMID- 7510309
TI  - Serological responses to different genotypes of hepatitis C virus in France.
AB  - The relationship between hepatitis C virus (HCV) genotypes and antibody status
      was studied in 104 chronic non-A, non-B hepatitis patients and asymptomatic HCV
      infected blood donors. On the basis of amplification of the nonstructural protein
      3 (NS3) coding region by PCR and hybridization with specific probes, 55 and 42
      patients were identified as being infected with type I and type II, respectively,
      according to the classification by H. Okamoto, K. Kurai, S. Okada, K. Yamamoto,
      H. Lizuka, T. Tanaka, S. Fukuda, F. Tsudaand, and S. Mishiro (Virology 188:331
      341, 1992). All samples were tested for antibodies to 5.1.1, C-100, C-33, and C
      22 proteins by a second-generation recombinant immunoblot assay. Among 97
      patients with known HCV genotypes, 31 of 42 patients infected with type II and 24
      of 55 infected with type I had antibodies against all four antigens (P < 0.01).
      In the type II-infected group, more patients had detectable antibodies to 5.11, C
      33, and C-22 proteins than in the type I group (P < 0.05). No difference was
      found in the serological response to C-100 between the two groups.

PMID- 7510311
TI  - Morphological diversity of Blastocystis hominis in sodium acetate-acetic acid
      formalin-preserved stool samples stained with iron hematoxylin.
AB  - The objective of this investigation was to study the morphological
      characteristics of Blastocystis hominis in sodium acetate-acetic acid-Formalin
      preserved stool samples. Routinely processed samples were examined for
      morphological detail, including size, shape, nuclear detail, and central body
      characteristics. Morphological findings revealing the importance of recognizing
      B. hominis in the diagnostic laboratory are described.

PMID- 7510313
TI  - Altered relation between granulocyte elastase and alpha-2-macroglobulin in
      gingival crevicular fluid from sites with periodontal destruction.
AB  - Granulocyte elastase activity and alpha-2-macroglobulin (alpha-2-MG) were studied
      in the gingival crevicular fluid (GCF) from 3 categories of sites in 6 patients
      with gingivitis and 6 patients with periodontitis. 6 inflamed sites in each
      gingivitis patient were sampled on paper strips and 12 sites, 6 with and 6
      without attachment loss and periodontal pockets, were selected in each
      periodontitis patient. To avoid the influence of increase GCF volume from deep
      pockets, the elastase activity and the alpha-2-MG were calculated per microliters
      of GCF. The proteolytic activity of elastase was measured with a low molecular
      weight substrate and the antiprotease, alpha-2-MG, with ELISA. The measured
      activity could be ascribed to elastase that had been released into the gingival
      tissues and into the GCF prior to sampling. In the periodontitis patients, the
      sites with tissue destruction had a significantly higher elastase activity per
      site and per microliters GCF and a significantly lower alpha-2-MG per microliters
      than the 2 other categories of sites without tissue destruction. The destructive
      inflammation seems to be associated with increased release of elastase, either
      from more numerous or from more active granulocytes and with an increased
      proteolytic consumption of the inhibitor accompanied by the fast elimination of
      the protease-inhibitor-complex. In conclusion, the study shows a strong
      relationship between elastase activity and tissue destruction, a finding that
      supports the pathogenic theory of an involvement of granulocytes and their
      proteolytic enzymes in the mechanism of periodontal destruction.

PMID- 7510314
TI  - Tangential symbols: using visual symbolization to teach pharmacological
      principles of drug addiction to international audiences.
AB  - Visual art was used to teach the biopsychiatric model of addiction to audiences
      in the Caribbean, Europe and Mideast. Art slides were tangentially linked to
      slides of pharmacological data. Stylistically dense art was processed by the
      intuitive right brain while spare notational pharmacological data was processed
      by the intellectual (rationalistic) left brain. Simultaneous presentation of
      these data enhanced attention and retention. This teaching paradigm was based on
      the nonliterate methods developed by Medieval architects and refined by Italian
      Renaissance philosopher, Marsilio Ficino.

PMID- 7510312
TI  - Utility of gram stain in evaluation of sputa from patients with cystic fibrosis.
AB  - The utility of sputum Gram stain in assessing salivary contamination and in
      predicting the presence of pathogens on the basis of morphology was investigated
      in 287 respiratory specimens from patients with cystic fibrosis. Where
      acceptability for culture was defined as a leukocyte/squamous epithelial cell
      ratio of > 5, 76.6% (220 of 287) of respiratory specimens received in the
      laboratory were considered acceptable. Unacceptable specimens were more common in
      younger patients. The positive predictive value of the Gram stain for growth from
      acceptable sputum samples was 98% for Pseudomonas aeruginosa, 84.4% for
      Pseudomonas cepacia, 86.3% for Staphylococcus aureus, and 100% for Haemophilus
      influenzae. In cystic fibrosis patients, as has been reported for respiratory
      specimens in general, Gram stain of respiratory specimens in helpful for
      interpreting culture results.

PMID- 7510315
TI  - Postcontrast MR arthrography in assessment of cartilage lesions.
AB  - OBJECTIVE: Although MR has been proven effective in evaluating many components of
      the musculoskeletal system, including ligaments, fibrocartilage, muscle, and bone
      marrow, its role in the evaluation of articular cartilage remains controversial.
      Recent studies have demonstrated that intraarticular injection of Gd-DTPA [MR
      arthrography (MRA)] improves the detection of cartilage abnormalities in
      cadaveric specimens. The aim of this study was to determine the efficacy of MRA
      for the detection of naturally occurring cartilage lesions in a clinical
      population. MATERIALS AND METHODS: Sixty knees of 58 patients were studied with a
      three-dimensional (3D) T2*-weighted GE sequence (FISP) both before and after and
      a T1-weighted (T1W) SE sequence after the intraarticular injection of a 2 mmol/L
      Gd-DTPA solution. All knees subsequently underwent arthroscopy or arthrotomy.
      RESULTS: The MRA sequences performed significantly better (kappa = 0.85) than the
      routine FISP sequences (kappa = 0.39) in both the detection and the staging of
      cartilage abnormalities. The MRA FISP sequence (kappa = 0.91) performed slightly
      better than the MRA T1W sequence (kappa = 0.85), but there was no statistically
      significant difference between the two sequences. No complications from the
      intraarticular injection of contrast material occurred. CONCLUSION: Therefore,
      MRA appears to be an effective and safe method for the evaluation of articular
      cartilage abnormalities.

PMID- 7510316
TI  - Effects of the antidepressant drug tianeptine on plasma and platelet serotonin of
      depressive patients and healthy controls.
AB  - We have examined the effects of a single 12.5 mg dose and of 12 weeks treatment
      up to 37.5 mg daily with tianeptine, a new antidepressant drug that potentiates
      in vivo the uptake of serotonin (5-HT). On day 0, tianeptine reduced plasma 5-HT
      concentration. This acute effect occurred also on subsequent examination days.
      However, long-term treatment tended (P < 0.06) to increase basal plasma 5-HT
      concentrations, in covariation with decreases of MADRS (Montgomery-Asberg
      Depression Rating Scale) and HARS (Hamilton Anxiety Rating Scale). Platelet 5-HT
      increased only in elderly patients, probably due to the higher plasma
      concentration of the drug in this group than in younger patients. These results
      show that the acute effects of therapeutic doses of tianeptine are consistent
      with an enhancement of the 5-HT uptake. However, long-term treatment does not
      result in a decreased plasma 5-HT, as might be expected from the acute effects of
      the drug.

PMID- 7510317
TI  - Nitric oxide synthase in motor neurons after axotomy.
AB  - Nitric oxide synthase (NOS), an enzyme involved in synthesis of nitric oxide
      (NO), has been localized in many diverse cell types. In the CNS and PNS, discrete
      neuron cell groups express NOS constitutively. Recent evidence indicates that NOS
      is inducible in neurons normally not expressing NOS. After transection of
      peripheral nerves, NOS expression was significantly up-regulated in the
      axotomized sensory ganglion cells, whereas in the corresponding motor neurons NOS
      was not induced unless axon regeneration was prevented and ensuing neuron death
      became massive. Studies on axotomy-induced NOS have been limited largely to
      spinal nerves, with only one reported in the vagus nerve. The aim of this study
      was to determine whether NOS induction in motor neurons of the brainstem after
      axotomy is regulated in a manner similar to that of the spinal cord. By NADPH
      diaphorase histochemistry and NOS immunocytochemistry, the status of NOS in
      neurons of the hypoglossal nucleus, dorsal motor nucleus of the vagus, and motor
      nucleus of the facial nerve was examined 2 weeks after unilateral transection of
      the respective cranial nerves, and the results were compared with those of spinal
      motor neurons after transection of the sciatic nerve. NOS, undetectable in
      neurons of the three cranial motor nuclei of sham-operated animals, was observed
      in about 30-50% of neurons in the cranial motor nuclei ipsilateral to axotomy,
      but it was not detected in spinal motor neurons after axotomy. NOS localized in
      axotomized cranial motor neurons was unrelated to NOS of macrophages or
      endothelial cells. There was no appreciable cell loss from axotomy at this period
      except in the dorsal motor nucleus of the vagus, where some loss was observed.
      The results indicate that there is a fundamental difference in the regulation of
      NOS expression between motor neurons of the cranial and spinal nerves. The
      possible role of NOS/NO acting as cytoprotective or cytotoxic agent on injured
      motor neurons is discussed. Motor neurons of cranial and spinal nerves may serve
      as a useful model to further define the roles of NOS/NO in neurons, especially
      after traumatic injury.

PMID- 7510318
TI  - Immunolocalization of stratum corneum chymotryptic enzyme in human skin and oral
      epithelium with monoclonal antibodies: evidence of a proteinase specifically
      expressed in keratinizing squamous epithelia.
AB  - Stratum corneum chymotryptic enzyme (SCCE) is a recently discovered serine
      proteinase, which has been purified from human plantar stratum corneum. Evidence
      has been presented that it may play a role in the terminal stages of epidermal
      turnover, especially in desquamation. Two mouse monoclonal antibodies (MAb) were
      raised, TE4b and TE9b, that reacted specifically with SCCE in
      immunoprecipitation, immunoblotting, and gel-exclusion chromatography. When used
      in immunohistochemical experiments with the peroxidase-anti-peroxidase method,
      both MAb detected an antigen located in high suprabasal keratinocytes of the
      epidermis in normal human skin and at the vermilion border of the lip, with
      maximal staining of the stratum granulosum. In the hair follicles the MAb reacted
      with the inner root sheet only. In human oral mucosa the MAb stained the high
      suprabasal epithelial cells of the hard palate. This is a site where the
      epithelium forms an orthokeratotic stratum corneum. There was no specific
      staining of the epithelium of the lip mucosa or the buccal mucosa, where the
      epithelium does not form a stratum corneum under non-pathological conditions. A
      correlation therefore seems to exist between the presence of SCCE in high
      suprabasal cells and the ability of the epithelium to form an orthokeratotic
      cornified layer. We suggest that SCCE is specifically expressed in keratinizing
      squamous epithelia and that its expression may be part of the terminal
      differentiation program of this type of epithelium. These results also give
      further support to the idea that SCCE may play a role in the turnover and/or
      formation of the stratum corneum.

PMID- 7510320
TI  - A comparison of techniques for localizing actin and tubulin in hyphae of
      Saprolegnia ferax.
AB  - We have evaluated protocols for immunofluorescence (IF) staining of the
      potentially interacting actin filaments (F-actin) and microtubules in hyphae of
      Saprolegnia ferax, using rhodamine-phalloidin (RP) and freeze-substitution
      electron microscopy (FSEM), respectively, as standards for their distribution.
      Saprolegnia has four distinguishable cortical F-actin populations with
      characteristic organizations and RP- and actin-IF-staining affinities, all of
      which could be labeled with both probes after some protocols. Other protocols
      stained only some of the populations. Cortical F-actin was always more
      reproducibly and sharply stained with RP than IF, indicating that the former is
      the probe of choice for F-actin in these cells. Although no single IF protocol
      revealed all of the F-actin and microtubule populations, showing the potential
      need to optimize protocols for specific antibodies, simultaneous localization was
      readily achieved by dual labeling with RP and tubulin IF. Tubulin IF patterns
      differed from FSEM: mitotic spindles were revealed but not the more abundant
      prophase microtubule arrays, and the cytoplasmic microtubules were subapically
      displaced and bundled into long cables. These cables, which apparently linked
      nuclei, indicate a previously undetected involvement in nuclear spacing. The
      tubulin antibody successfully used for IF failed to recognize any proteins in
      immunoblots, indicating that immunoblots may not always be a useful indicator of
      success with IF.

PMID- 7510319
TI  - Sensitivity of immunohistochemistry and polymerase chain reaction in detecting
      prostate cancer cells in bone marrow.
AB  - Occult micrometastases detected by immunohistochemistry have prognostic
      significance in patients with localized breast cancer. To determine the
      usefulness of this technique and of polymerase chain reaction in detecting occult
      prostate cancer, we evaluated the sensitivity and specificity of
      immunohistochemistry and polymerase chain reaction amplification of mRNA to
      detect prostate cancer cells in bone marrow samples. We used cells from an
      established prostate cancer cell line (LNCAP) mixed with lymphocytes at various
      dilutions from 10(5) cancer cells in 10(6) lymphocytes to 1:10(6). Both
      techniques had a 100% specificity and identified cancer cells at all dilutions.
      Polymerase chain reaction was more sensitive than immunohistochemistry at the
      lowest dilutions (10(-5) and 10(-6), p = 0.033). We have evaluated seven patients
      with prostate cancer for micrometastases. Both of the patients with known
      metastatic prostate cancer and one of the five patients with clinically localized
      tumors had micrometastases. Detection of micrometastases may be useful in the
      staging of prostate cancer.

PMID- 7510321
TI  - Organ distribution in rats of two members of the low-density lipoprotein receptor
      gene family, gp330 and LRP/alpha 2MR, and the receptor-associated protein (RAP).
AB  - We investigated immunohistochemically the distribution in rats of the homologous
      proteins gp330 and the LDL receptor-related protein (LRP/alpha 2MR), and a
      receptor-associated protein (RAP), and the sites to which soluble exogenous RAP
      binds. We found gp330 in a restricted group of epithelial cells, including renal
      proximal tubule cells, podocytes, Type II pneumocytes, cells of the parathyroid,
      thyroid, epididymis, lining of the uterus, ependyma, retina, ciliary body, yolk
      sac, and placenta. In these cells gp330 was detected mainly at the cell surface,
      except for parathyroid and retinal epithelial cells, where diffuse cell staining
      was found. LRP/alpha 2MR was widely distributed in interstitial cells, notably in
      fibroblasts and macrophages, and was also present in a selected group of
      epithelial or specialized cells, including hepatocytes, adrenal cortical cells,
      follicular cells of the ovary, cells of the choroid plexus, ciliary body,
      mesangial cells, and some neurons. In certain cells, notably hepatocytes and
      adrenal cortical cells, LRP/alpha 2MR was detected mainly on the surface, but in
      others, including macrophages, fibroblasts, and epithelial cells of the choroid
      plexus and ciliary body, staining throughout the cell was seen. The only cells
      that clearly expressed both LRP/alpha 2MR and gp330 were retinal and ciliary
      epithelial cells. RAP was found in intracellular vesicles in all cells that
      expressed gp330 or LRP/alpha 2MR. RAP was not definitely detected on the cell
      surface. Binding sites for RAP were found on the surface of those cells with
      surface gp330 or LRP, and also throughout the cytoplasm in cells with diffuse
      cellular LRP/alpha 2MR or gp330. Because of their different locations, we
      conclude that gp330 and LRP/alpha 2MR serve distinct functions in vivo, despite
      similarities in ligand-binding properties observed in vitro. Since RAP is found
      largely within cells, its major physiological function may be concerned with
      intracellular assembly or trafficking of the receptors to which it binds.

PMID- 7510322
TI  - Partial protection against genital reinfection by immunization of guinea-pigs
      with isolated outer-membrane proteins of the chlamydial agent of guinea-pig
      inclusion conjunctivitis.
AB  - Because partial protection against reinfection is induced by experimental
      infection in the guinea-pig model of genital chlamydial infection, we sought to
      induce immunity by immunization. Female guinea-pigs were immunized subcutaneously
      with the major outer-membrane protein (MOMP) and the 61 kDa cysteine-rich outer
      membrane protein (61 kDa) of the agent of guinea-pig inclusion conjunctivitis
      (GPIC) eluted from SDS-polyacrylamide gels (SDS-MOMP, SDS-61 kDa). Post
      immunization sera and secretions contained antibodies to the SDS-purified
      proteins at high titre as measured by immunoblotting, whereas enzyme immunoassays
      (EIA) using whole elementary bodies as antigen showed significantly lower titres
      (P < 0.001). Likewise, blastogenic responses of peripheral mononuclear cells to
      GPIC elementary bodies were weak. Animals immunized with SDS-MOMP and SDS-61 kDa
      were fully susceptible to intravaginal challenge, as were control animals
      immunized with buffer without protein. Another group of animals were immunized
      with material prepared by extraction of chlamydial outer-membrane complexes with
      octyl beta-D-glucopyranoside (OGP) and dithiothreitol, which consisted largely of
      MOMP (OGP-MOMP). In contrast to the SDS-MOMP group, sera and secretions in the
      OGP-MOMP group showed high titres in EIA, and high titre antibodies to MOMP by
      immunoblot; however, most animals also had antibodies to 61 kDa, 72 kDa and ca.
      84 kDa outer-membrane proteins. OGP-MOMP animals were partially protected against
      genital challenge as evidenced by low inclusion scores compared to control
      animals, although duration of infection measured by culture isolation was similar
      to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510323
TI  - Calcineurin-dependent growth of an FK506- and CsA-hypersensitive mutant of
      Saccharomyces cerevisiae.
AB  - The immunosuppressants FK506 and cyclosporin A (CsA) bound to their receptors,
      FKBP12 or cyclophilin, inhibit the Ca2+/calmodulin-dependent protein phosphatase,
      calcineurin, preventing T cell activation or, in yeast, recovery from alpha
      mating factor arrest. Vegetative growth of yeast does not require calcineurin,
      and in strains sensitive to FK506 or CsA, growth is inhibited by concentrations
      of drug much higher than those required to inhibit T cell activation or recovery
      from mating factor arrest. We now describe the isolation of a mutant of
      Saccharomyces cerevisiae which is 100-1000-fold more sensitive to the growth
      inhibitory properties of these drugs. The mutation (fks1) also confers a slow
      growth phenotype which is partially suppressed by exogenously added Ca2+ and
      exacerbated by EGTA. Simultaneous disruption of the two genes (CNA1 and CNA2)
      encoding the alternative forms of the catalytic A subunit of calcineurin, or of
      the gene (CNB1) encoding the regulatory B subunit, is lethal in an fks1 mutant.
      Disruption of the gene encoding FKBP12 (FKB1) or the major, cytosolic cyclophilin
      (CPH1) in fks1 cells results in the loss of hypersensitivity to the relevant
      drug. Overexpression of CNA1 or CNA2, in conjunction with CNB1, results in a
      significant decrease in hypersensitivity to FK506 and CsA. The results show that
      the hypersensitivity of the fks1 mutant is due to the inhibition of calcineurin
      phosphatase activity by the receptor-drug complexes. The growth dependence of the
      mutant on the Ca2+/calcineurin signal pathway provides an important tool for
      studying in yeast certain aspects of immune suppression by these drugs.

PMID- 7510324
TI  - Typing of Clostridium difficile strains by PCR-amplification of variable length
      16S-23S rDNA spacer regions.
AB  - To develop a rapid and accurate method of typing large numbers of clinical
      isolates of Clostridium difficile, four regions of the rRNA operon [A, 15-1407
      and B, 907-1407 (16S-16S); C, 1392-507 and D, 907-507 (16S-23S)] were enzymically
      amplified from 24 strains. When region A was hybridized to HindIII-digested
      genomic DNA isolated from C. difficile strains, all of the variable length
      restriction fragments hybridized. When region B was hybridized to HindIII
      digested genomic DNA isolated from C. difficile strains, a set of variable length
      restriction fragments (Group II) hybridized predominantly. When region C was
      separated by agarose gel electrophoresis, a series of products ranging in size
      from approximately 800-1300 bp was obtained. When regions C and D were digested
      with HindIII, a constant region of 430 bp was found in both products and in all
      strains. From the above experiments it was concluded that the variable length
      Group II restriction fragments and the variable length region C amplification
      products were due to variable length 16S-23S spacer regions between alleles of
      the one strain. When region C amplification products were separated by denaturing
      PAGE, 16 variable length rRNA alleles (rrnA-P) were demonstrated from 24 C.
      difficile strains ranging in size from 852-1210 bp. After analysis with maximum
      parsimony, the 24 strains were divided into 14 ribotypes.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7510325
TI  - Antimicrobial activity and biosynthesis of indole antibiotics produced by
      Xenorhabdus nematophilus.
AB  - We have investigated the mechanism of action and physiology of production of the
      indole derivative antibiotics produced by the nematode-associated,
      entomopathogenic bacterium Xenorhabdus nematophilus. Maximum antibiotic
      concentration was reached during the late stationary phase of growth, and the
      antibiotic yield was appreciably enhanced by supplementation with tryptophan.
      Antibiotic biosynthesis apparently involved the removal of the side-chain
      carboxyl (C-1) carbon of tryptophan. The C-3 methylene carbon of tryptophan, on
      the other hand, was retained. The purified indole antibiotic was effective
      against both Gram-positive and Gram-negative bacteria at low to moderate
      concentrations causing a severe inhibition of RNA synthesis, accompanied by a
      less severe effect on protein synthesis. An isogenic pair of Escherichia coli
      strains differing at the relA locus was used to demonstrate that the swift
      reduction in total RNA synthesis is related to an antibiotic-induced accumulation
      of the regulatory nucleotide, ppGpp, in susceptible bacteria. The E. coli relA
      mutant, which does not exhibit any discernible increase in ppGpp upon antibiotic
      treatment, showed no decrease in growth or RNA synthesis. Using this antibiotic,
      it was also observed that ppGpp may be employed as a metabolic regulator in
      bacteria such as Pseudomonas putida, which have not previously been reported to
      employ ppGpp as a regulatory molecule. We propose that the indole derivative
      antibiotic exerts growth inhibitory control in susceptible bacteria by greatly
      enhancing synthesis of ppGpp, resulting in a rapid inhibition of RNA synthesis.

PMID- 7510326
TI  - Cloning and characterization of a tryptophanase gene from Enterobacter aerogenes
      SM-18.
AB  - A tryptophanase gene from Enterobacter aerogenes SM-18 was cloned and sequenced.
      The structural gene for tryptophanase, tnaA, consisted of 1389 bp encoding 462
      amino acid residues, and its nucleotide sequence and deduced amino acid sequence
      showed significant homology to those of tnaA from Escherichia coli K12. A short
      open reading frame consisting of 31 amino acid residues was found upstream of
      tnaA, and it showed some similarity to the E. coli tnaC gene known to be a cis
      acting regulatory element for transcription. A partial open reading frame
      homologous to the 5' end of E. coli tnaB was observed at the 3'-flanking region
      of tnaA. These genes may thus constitute an operon as in E. coli.

PMID- 7510327
TI  - HN proteins of human parainfluenza type 4A virus expressed in cell lines
      transfected with a cloned cDNA have an ability to induce interferon in mouse
      spleen cells.
AB  - Primary monkey kidney cells infected with human parainfluenza type 4A virus (HPIV
      4A) were treated with various concentrations of formaldehyde. Formaldehyde
      (0.275%) treatment completely blocked virus production. However, when mouse
      spleen cells were cocultured with the fixed virus-infected cells, interferon was
      produced in the culture fluid. On the other hand, when mouse spleen cells were
      incubated with the fixed virus-infected cells in the presence of anti-HPIV-4A
      antiserum or a mixture of anti-HN protein monoclonal antibodies, interferon
      activity could scarcely be detected in the culture fluid. These findings
      indicated that the fixed virus-infected cells had an ability to induce interferon
      in mouse spleen cells and that the HN protein was related to interferon
      induction. Subsequently, a recombinant plasmid was constructed by inserting the
      cDNA of the HN gene of HPIV-4A into a pcDL-SR alpha expression vector. Mouse
      spleen cells produced interferon when cocultured with COS7 cells transfected with
      the recombinant plasmid, but did not when cocultured with COS7 cells transfected
      with the vector alone. Furthermore, we established HeLa cells constitutively
      expressing HPIV-4A HN (HeLa-4aHN cells) or F protein (HeLa-4aF cells). Type I
      (alpha/beta) interferon was detected in culture fluids of mouse spleen cells with
      HeLa-4aHN cells, but was not detected in those with HeLa-4aF cells. Therefore, it
      was concluded that the HN glycoproteins on the cell surface were sufficient for
      interferon induction to occur.

PMID- 7510328
TI  - Identification of cytotoxic T cell epitopes on the VP3 and VP6 rotavirus
      proteins.
AB  - It has been shown previously that the viral glycoprotein VP7 is a major target of
      cytotoxic T lymphocytes (CTLs) induced by bovine rotavirus RF in C57BL/6 mice.
      Here we show that these RF-specific CTLs recognize target cells infected with a
      recombinant vaccinia virus (rVV) expressing the SA11 (simian rotavirus) VP6 but
      not those infected with rVVs that express RF VP1, VP2 or VP3 core proteins. After
      immunization of mice with insect cells infected with recombinant baculoviruses
      that express the corresponding RF proteins a strong specific CTL response was
      generated against target cells infected with VP6 rVV and VP3 rVV, a weak one
      against the VP2 rVV but none against the VP1 rVV. Kb-restricted CTL epitopes were
      identified on VP6 and VP3 using allele-specific motifs. When peptides
      corresponding to these epitopes were used to restimulate in vitro the spleen
      cells from RF-immunized mice, CTLs specific for each peptide and its
      corresponding rVV were induced.

PMID- 7510331
TI  - Stem cell factor is a neurotrophic factor for neural crest-derived chick sensory
      neurons.
AB  - We have found that stem cell factor (SCF) selectively enhances the survival of
      cultured embryonic chick dorsal root ganglia (DRG) neurons. Neurons grown in the
      presence of SCF expressed both neurofilament 150 kDa subunit and calcitonin-gene
      related peptide. SCF does not, however, enhance the survival of parasympathetic,
      placode-derived sensory or sympathetic neurons in culture. Combining SCF with
      brain-derived neurotrophic factor or neurotrophin-3, but not with NGF, maintains
      more neurons than either factor alone, suggesting that these factors have
      partially overlapping activities. SCF preferentially rescues small neurons from
      the DRG. Labeling studies with bromodeoxyuridine indicate that the neurons
      sustained by SCF are not differentiating from a dividing progenitor.

PMID- 7510330
TI  - A placebo-controlled trial of isoprinosine in patients with multiple sclerosis.
AB  - Isoprinosine was used under double-blind, randomised, and placebo-controlled
      conditions in 52 patients with relapsing/remitting or progressive multiple
      sclerosis. All patients received pulsed treatment with methylprednisolone. There
      was no significant effect of treatment on clinical disability or the accumulation
      of MRI abnormalities, after correction of results for multiple comparisons. It is
      concluded that isoprinosine is not effective therapy for multiple sclerosis.

PMID- 7510333
TI  - Serotonin immunoreactivity is contained in one physiological cell class in the
      rat rostral ventromedial medulla.
AB  - Neurons in the rostral ventromedial medulla (RVM) are the major source of
      serotonergic projections to the dorsal horn. A large body of evidence implicates
      RVM serotonergic neurons in the modulation of spinal nociceptive transmission.
      Three physiological classes of RVM neurons, on, off, and neutral cells, are
      postulated to have different nociceptive modulatory effects on spinal nocifensor
      reflexes. This study was undertaken to determine which RVM cell class(es)
      contains 5-HT. In anesthetized rats, RVM neurons were identified by their
      responses to noxious cutaneous stimuli, intracellularly labeled, and processed
      for 5-HT immunocytochemistry. Labeled neurons were examined with epifluorescence
      and imaged using a confocal laser microscope. A total of 25 RVM neurons were
      intracellularly labeled. No off (n = 9) or on (n = 8) cells were serotonergic.
      Half of the neutral cells (4 of 8) demonstrated 5-HT immunoreactivity. These
      results call for a reevaluation of the mechanisms of RVM modulatory influence on
      spinal cord nociceptive transmission. The finding that some neutral cells are
      serotonergic strongly suggests that serotonergic neutral cells are involved in
      the modulation of spinal nociceptive transmission. Additionally, inhibition of
      spinal nociceptive transmission by off cells is unlikely to involve 5-HT release.
      Finally, since opioid administration does not alter the firing of RVM neutral
      cells, the results of the present study indicate that serotonergic RVM neurons do
      not directly mediate the effects of supraspinal opioids in the rat.

PMID- 7510332
TI  - Optic nerve injury alters basic fibroblast growth factor localization in the
      retina and optic tract.
AB  - Basic fibroblast growth factor (bFGF) is thought to be a trophic factor for
      several classes of neurons. Its distribution changes in response to cortical
      neural injury. We have determined the effect of injury to the optic nerve on
      localization of bFGF in the rodent retina and visual pathways. Our observations
      were confirmed by using different antisera and monoclonal antibodies. While
      photoreceptors normally contain virtually no bFGF, crushing the optic nerve
      causes a striking increase, over a period of several weeks, in the amount of bFGF
      in retinal photoreceptors. Since photoreceptors do not synapse directly upon the
      injured ganglion cells, intermediary cells must participate in the cascade of
      events that results in the elevated bFGF. In light of the observation that
      exogenous bFGF protects photoreceptors from photodamage (Faktorovich et al.,
      1992), this increase in bFGF in photoreceptors may explain, in part, why crushing
      the optic nerve protects photorecptors against photodamage (Bush and Williams,
      1991). Whereas bFGF is constitutively found in glia in the optic nerve, little
      bFGF is found in glia in the optic tract. However, damage to the optic nerve
      increases bFGF in astrocytes in the optic tract. This change occurs within days,
      suggesting that a relatively direct signal may intervene between the injured axon
      and the adjacent glial cells. Thus, despite the fact that the optic nerve and
      optic tract are contiguous structures through which axons of retinal ganglion
      cells project, the glial elements in these structures express distinct
      properties, because of differences in either glial subclasses or
      microenvironment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510329
TI  - Lentivirus cross-reactive determinants present in the capsid protein of equine
      infectious anaemia virus.
AB  - In this study we used immune sera from equine infectious anaemia virus (EIAV)
      infected horses which uniquely display broad reactivity with different lentivirus
      capsid proteins (CA) to characterize the cross-reactive determinants of
      lentivirus CA proteins. In particular, the role of the major homology region
      (MHR) of lentivirus CA proteins in this serological cross-reactivity was
      evaluated using both equine immune serum and murine monoclonal antibodies (MAbs)
      directed against the MHR segment of different lentiviruses. The results of our
      studies indicate that about 80% of sera from long-term experimentally infected
      ponies or naturally infected horses react with human immunodeficiency virus type
      1 CA in Western immunoblot assays. In addition, the cross-reactive determinants
      on the EIAV CA were localized within the immunodominant carboxyl terminus of the
      protein (residues 277 to 367). However, the cross-reactive determinants
      recognized by the equine sera do not appear to correlate with linear peptides
      from the carboxyl terminus of the EIAV CA, including the MHR. These results
      suggest cross-reactivity between more distant lentiviruses is associated with non
      linear determinants. In contrast, MHR-specific MAbs did react with linear
      peptides by ELISA and distinguished the primate lentiviruses from EIAV and feline
      immunodeficiency virus. These data support the concept of a highly conserved
      structural and antigenic organization among the CA proteins of lentiviruses from
      different species.

PMID- 7510334
TI  - Astroglial modulation of transient potassium current development in cultured
      mouse hippocampal neurons.
AB  - Hippocampal neurons exhibit three voltage-gated potassium currents, two transient
      currents and a delayed rectifier, that influence numerous aspects of
      electrogenesis including action potential duration and accommodation to sustained
      depolarization. These currents, termed A-, D-, and K-currents, respectively, can
      be distinguished based on kinetics, steady state inactivation characteristics,
      and sensitivity to 4-aminopyridine (see Wu and Barish, 1992b). We have compared
      the voltage-gated potassium currents in voltage-clamped pyramidally shaped
      cultured hippocampal neurons growing on or touching glial fibrillary acidic
      protein-expressing astroglia (termed on-glia or touching-glia neurons,
      respectively) with those in similar neurons growing directly on a coated glass
      substrate (termed off-glia neurons). We observed differences in the wave forms of
      total potassium current that correlated with the extent of astroglial contact.
      After 5-7 d in culture, A-current amplitude in off-glial neurons was
      approximately 19% of that of neurons growing in the normal (for culture) on-glia
      configuration. D-current amplitude tended to be larger in these off-glia neurons.
      Neurons in contact with astroglia had greater membrane area than off-glia
      neurons. Comparison of current densities (current at a fixed voltage normalized
      to capacitance and expressed in units of pA/pF) indicated that A-currents were
      the major component of transient potassium current in on- and touching-glia
      neurons, while D-currents were more dominant in off-glia neurons. Astroglia
      influenced membrane currents by a surface- or extracellular matrix-associated
      mechanism, rather than by free diffusion of a soluble factor, as differences were
      observed between closely adjacent neurons on the same coverslip. Living glia were
      required, as potassium currents in neurons grown on dried or methanol-fixed glia
      resembled those of off-glia neurons. On-glia neurons in cultures treated with an
      RNA synthesis inhibitor [DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole)]
      for 5-7 d had reduced whole-cell capacitance and A-current amplitude. This effect
      was localized to DRB actions on underlying astroglia, not on the neurons. Action
      potentials elicited by current injection varied with astroglial contact. In on
      glia neurons with relatively larger A-currents a delay was seen in the onset of
      firing after depolarization. In contrast, action potentials in off-glia neurons
      rose smoothly after initiation of depolarization. We conclude that astrocytes
      modulate the appearance of transient potassium currents in hippocampal pyramidal
      neurons by inducing development of A-current.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7510335
TI  - Correlation of nitric oxide synthase expression with changing patterns of axonal
      projections in the developing visual system.
AB  - A precise pattern of connections between the retina and central visual nuclei in
      the brain is established during development. Activity-dependent presynaptic
      mechanisms and NMDA receptor-mediated postsynaptic mechanisms are thought to play
      important roles in this developmental process. A model proposed for production of
      the newly described neurotransmitter, nitric oxide, involves presynaptic activity
      and activation of postsynaptic NMDA receptors. If present in the developing
      visual system, nitric oxide could represent a form of retrograde communication
      from postsynaptic to presynaptic cells that mediates the formation of the proper
      pattern of connections. This study used the diaphorase histochemical technique to
      detect the presence of nitric oxide synthase (NOS), the enzyme responsible for
      the production of nitric oxide, in the developing chick optic tectum. Results
      from this study showed that NOS is present in the developing tectum and that its
      expression coincides temporally with innervation by retinal axons. NOS expression
      reaches a peak at the time that refinement of the initial pattern of connections
      is occurring. WGA/HRP labeling of retinal axons confirmed that processes of NOS
      positive cells in the tectum extend well into the area of the ingrowing retinal
      axons. Histochemical results from eyeless chick embryos indicate that NOS
      expression is dependent on the presence of retinal axons, which suggests that
      retinal axons synapse on cells that express nitric oxide. Northern blot analysis
      using a cDNA probe to NOS from rat brain verified the histochemical results.
      These results are consistent with nitric oxide having a role in development of
      the proper pattern of connections in the chick retinotectal system.

PMID- 7510336
TI  - Serum concentrations of albumin, C-reactive protein, alpha 2-macroglobulin,
      prealbumin, fibronectin, fibrinogen, transferrin, and retinol binding protein in
      55 patients with hepatic glycogen storage diseases.
AB  - Hepatic glycogen storage diseases are hereditary metabolic disorders involving
      the metabolism of glycogen. This study was designed to investigate the serum
      protein status in such diseases. Fifty-five patients with glycogen storage
      disease types I, III, VI, and IX, whose ages ranged from 1 month to 27 years,
      were included in this work. C-reactive protein, fibrinogen, alpha 2
      macroglobulin, albumin, transferrin, fibronectin, retinol binding protein, and
      prealbumin serum concentrations were measured in each patient. In patients
      affected with type I glycogen storage disease, serum concentrations of alpha 2
      macroglobulin, fibrinogen, C-reactive protein, and transferrin were significantly
      increased. In patients with types III, VI, and IX glycogen storage diseases, the
      concentration of alpha 2-macroglobulin was the only one that was significantly
      increased. Thus, even though this study raises more questions than it answers, it
      seems likely that the hepatic synthesis of some proteins may be increased in
      patients affected by hepatic glycogen storage diseases. This may indicate some
      degree of mild hepatic dysfunction in such metabolic disorders. However, further
      investigations are required to elucidate the discrepancies observed among the
      different types of diseases.

PMID- 7510337
TI  - Production of a human monoclonal antibody to normal basal and squamous cell
      carcinoma-associated antigen.
AB  - A human monoclonal antibody, BM2, was produced by a hybridoma line generated by
      fusion of lymph node cells from a patient with squamous cell carcinoma (SCC) of
      the tongue with human B-lymphoblastoid cell line HO-323. BM2, an IgM class
      antibody, was reactive with all of the SCC cell lines tested. Frozen sections of
      normal and malignant tumor specimens were investigated to examine the reactivity
      of BM2 towards them. All 35 oral SCC specimens reacted with BM2. Normal
      stratified squamous epithelium showed positive staining in basal cells, but no
      staining was seen in other layers of the stratified epithelium, simple
      epithelium, and tissues of nonepithelial origin. Ductal basal cells of normal
      salivary gland also showed positive staining. Western blotting and
      immunoprecipitation analysis revealed that BM2 recognized 52 kDa membrane
      associated protein. BM2 may therefore be a useful tool for biological and
      clinical studies of SCC.

PMID- 7510338
TI  - Immunohistochemical distribution of collagens type I, III, IV and VI, of undulin
      and of tenascin in oral fibrous hyperplasia.
AB  - The distribution of collagens type I, IV and VI, of procollagen type III, of
      undulin and of tenascin was studied in 10 lesions which were clinically and
      histologically diagnosed as localized oral fibrous hyperplasias. The
      immunohistochemical distribution of these proteins was similar to that observed
      for normal oral mucosa. Undulin showed a pattern of parallel fibers throughout.
      Collagen type VI was pronounced in the subepithelial connective tissue, whereas
      the collagen fiber bundles were equally reactive for collagens type I and III.
      Tenascin was observed close to the subepithelial basement membrane and in
      proximity to collagen fiber bundles in the upper connective tissue. The present
      findings indicate that oral fibrous hyperplasias that are probably caused by
      inflammation or chronic irritation show the differentiated and ordered pattern of
      extracellular matrix proteins characteristic of normal oral mucosa.

PMID- 7510339
TI  - Biocompatibility of visible light-cured resin systems in prosthodontics.
AB  - Frequently dental products are introduced that have had little or no biologic
      testing. Cell culture systems that traditionally have been used for the study of
      cellular responses have recently been used to assess biocompatibility. This
      article reviews various cellular toxicity assays and their application to the
      resin systems used in clinical prosthodontics.

PMID- 7510342
TI  - Involvement of a GNRA tetraloop in long-range RNA tertiary interactions.
AB  - Terminal loops with a GNRA consensus sequence are widespread in RNA. It has been
      suggested that these loops act as "anchors" during tertiary folding, by
      interacting in a sequence-specific way with helices at distant locations along
      the molecule. We now show that a GUGA loop changes state upon disruption of the
      tertiary architecture of a self-splicing group I intron. Successful replacement
      of the postulated loop-helix contact by classical base-pairing points to binding
      of the loop into the shallow (minor) groove of the helix, as also indicated by
      partial restoration of ribozyme stability upon a specific double nucleotide
      substitution.

PMID- 7510341
TI  - In vitro and in vivo activities of reduced-size antagonists of luteinizing
      hormone-releasing hormone.
AB  - A novel series of octapeptide LHRH antagonists was designed on the basis of the
      structure of the (2-9) fragment of a LHRH agonist. By adopting a systematic SAR
      study, we were able to improve first the in vitro activity and then the in vivo
      LH suppression, raising them up to the range of the decapeptide antagonists
      NalGlu (51) and A-75998 (50), resulting in A-76154 (49). The octapeptide
      antagonist A-76154 is the most potent reduced-size LHRH antagonist reported. It
      suppresses LH in the castrated rat by over 80% for a period of 4 h following sc
      bolus administration of 30 micrograms/kg.

PMID- 7510340
TI  - Tyrosine kinase inhibitors. 2. Synthesis of 2,2'-dithiobis(1H-indole-3
      alkanamides) and investigation of their inhibitory activity against epidermal
      growth factor receptor and pp60v-src protein tyrosine kinases.
AB  - A series of amide analogues of the 2,2'-dithiobis(1H-indole-3-alkaonic acid)
      class of tyrosine kinase inhibitors have been prepared, by reaction of 1H-indole
      3-alkanamides (8) with S2Cl2, and separation of the desired disulfides from the
      initial mixtures of mono-, di-, and trisulfides formed. These amides were
      evaluated in vitro against epidermal growth factor receptor and pp60v-src protein
      tyrosine kinases. Inhibitory activity against EGF receptor tyrosine kinase was
      chain-length dependent, with the propanamides being the most effective. Hydrogen
      bond donor capabilities in the amide function did not appear to be necessary,
      with an N-benzylamide being the most potent (IC50 = 0.85 microM). Further
      substitution on the benzyl ring did not increase potency, and substitution in the
      alpha-position of the propanamide side chain was acceptable. A water-soluble
      alpha-NH2 derivative showed good inhibitory activity toward the enzyme, was a
      potent inhibitor of cell growth in fibroblasts, and selectively inhibited
      intracellular tyrosine phosphorylation patterns. The nonreceptor kinase pp60v-src
      was in general much more sensitive than EGF receptor kinase to inhibition by
      these compounds, but with less pronounced structure-activity relationships.

PMID- 7510343
TI  - Subchronic (12-week) inhalation toxicity study of methanol-fueled engine exhaust
      in rats.
AB  - To evaluate the inhalation toxicity to rats of exhaust at low concentration for
      longer periods, Fischer 344 rats were exposed to 3 concentrations of exhaust
      generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without
      catalyst for 8 h/d, 6 d/wk for 4, 8, or 12 wk. Concentration- and time-dependent
      increase carboxyhemoglobin in the erythrocytes and decrease in cytochrome P-450
      in the lungs were observed in all treated groups. Furthermore, significant
      increases in plasma formaldehyde were observed in all treated groups.
      Furthermore, significant increases in plasma formaldehyde were observed in the
      group exposed to the highest concentration of exhaust (carbon monoxide, 89.8 ppm;
      formaldehyde, 2.3 ppm; methanol, 8.1 ppm; nitrogen oxides, 22.9 ppm; nitrogen
      dioxide, 1.1 ppm) for 8 or 12 wk. No change of plasma folic acid was observed in
      any group, and no methanol or formic acid was detected in the plasma in any
      animals. Histopathologically, exposure-related changes were found only in the
      nasal cavity of the high-concentration group. Slight hyperplasia/squamous
      metaplasias of the respiratory epithelium lining the nasoturbinate and
      maxilloturbinate were observed after 4 wk of exposure, and the incidences and
      degrees of these lesions increased slightly with the exposure time. No changes
      were found in the olfactory epithelium of the nasal cavity. As judged by optical
      microscopy, the exhaust concentration with no effect on the nasal cavity under
      the experimental conditions was concluded to be the medium concentration level
      containing 0.55 ppm formaldehyde. In the present study, however, concentration-
      and time-dependent increase of carboxyhemoglobin in the erythrocytes and decrease
      of the lung P-450 level were observed. Therefore, further study on more long-term
      inhalation of lower concentrations of exhaust might be needed.

PMID- 7510344
TI  - Response of metastasized sex cord gonadal stromal tumor of the testis to
      cisplatin-based chemotherapy.
AB  - A 34-year-old man underwent left hemicastration for malignant unclassified sex
      cord gonadal stromal tumor. At 6 months pulmonary metastases developed and the
      patient received 3 courses of chemotherapy consisting of cisplatin, bleomycin and
      etoposide. A residual focus in the right lung was excised and proved to be viable
      tumor. He then received 2 adjuvant courses of cisplatin, etoposide and
      ifosfamide. Six months later he was without evidence of disease. A review of the
      literature revealed 21 previous cases of malignant unclassified sex cord gonadal
      stromal tumor. Although chemotherapy usually fails in treating Leydig cell tumors
      our case corroborates 6 previous reports of favorable response to cisplatin-based
      chemotherapy. This finding suggests that different subtypes of sex cord gonadal
      stromal tumor respond differently to chemotherapy.

PMID- 7510345
TI  - Somatic allelic loss at the DCC, APC, nm23-H1 and p53 tumor suppressor gene loci
      in human prostatic carcinoma.
AB  - We present a restriction fragment length polymorphism (RFLP) analysis of 29
      benign and 30 malignant prostatic tumors, using polymorphic DNA probes to the
      putative tumor suppressor genes DCC (Deleted in Colorectal Carcinoma; chromosome
      18q21.3), nm23-H1 (17q21.3), APC (Adenomatous Polyposis Coli; 5q21) and p53
      (17p13). Six of 23 evaluable cancers (26%) showed loss of heterozygosity (LOH) at
      DCC; 5 were advanced stage and one was clinically localized (p < 0.05). Mapping
      18q deletions, another (advanced) cancer showed LOH at a locus distal to DCC
      (18q22), but no LOH at DCC. Three of 15 evaluable cancers (20%), all advanced,
      showed LOH at APC. Three of eight (38%) cancers, of which 2 were advanced, showed
      LOH at p53. One high grade/stage cancer of 21 (5%) showed LOH at nm23-H1 (and
      also at DCC). Combining data, allelic losses at either DCC, APC, or p53 genes
      were seen in 13% of localized cancers, but in 71% of advanced cancers (p <
      0.002). Allelic loss involving nm23-H1 is rare in prostatic carcinoma. We suggest
      that loss of tumor suppressor genes DCC and/or an unidentified gene located
      distally on chromosome 18q, APC, or p53 may influence progression in prostatic
      carcinoma.

PMID- 7510346
TI  - Collagen cross-link metabolites in urine as markers of bone metastases in
      prostatic carcinoma.
AB  - The efficacy of radionuclide bone scans in monitoring metastatic bone activity
      remains controversial. Objective measurement of bone tumor burden would be useful
      for the evaluation of new therapies for metastatic carcinoma of the prostate. The
      recent discovery of the urinary excretion of pyridinoline (cross-link of mature
      collagen found in cartilage and bone) and deoxypyridinoline (collagen cross-link
      specific to bone) measured by high pressure liquid chromatography has provided
      sensitive specific indexes of cartilage and bone breakdown in rheumatoid
      arthritis, osteoporosis and metabolic bone diseases. We compared the urinary
      excretion of deoxypyridinoline,pyridinoline and hydroxyproline relative to
      urinary creatinine (nmol./mmol.creatinine) in 27 patients with benign prostatic
      hyperplasia (patient age 70.0 +/- 8.5 years, standard deviation), 29 with
      clinically confined prostate cancer (age 70.2 +/- 9.7 years), and 26 with
      prostate cancer and bone metastases (age 71.1 +/- 7.7 years). No diurnal
      variation of deoxypyridinoline or pyridinoline urinary excretion was detected in
      5 patients with metastases. Urinary excretion of pyridinoline and
      deoxypyridinoline was significantly greater in patients with metastatic carcinoma
      of the prostate compared with patients with either benign prostatic hyperplasia
      (Mann-Whitney-Wilcoxon rank sum analysis, p < 0.00004 and 0.002, respectively) or
      localized prostate cancer (Mann-Whitney-Wilcoxon, p < 0.00001 and 0.00005,
      respectively). Urinary hydroxyproline levels failed to separate the 3 groups.
      Pyridinoline and deoxypyridinoline excretion in prostate cancer patients with
      metastases directly correlated with bone scan Soloway scores (r = 0.55, p < 0.005
      and r = 0.57, p < 0.004 respectively), whereas serum prostate specific antigen
      did not (r = 0.36, p = 0.08). Serial measurements of pyridinoline and
      deoxypyridinoline progressively increased in 3 patients with clinical progression
      documented by new metastatic lesions by bone scan. Measurement of pyridinoline
      and deoxypyridinoline excretion cannot diagnose metastatic disease. However,
      these markers should be evaluated further for quantitative assessment of bone
      metastases.

PMID- 7510347
TI  - [Serious bacterial infections in patients with hematologic disorders].
AB  - In patients with hematologic disorders, especially, leukemias and lymphomas,
      complicated bacterial infection frequently becomes serious. Main predisposing
      factors are (1) the disease and its chemotherapy (2) granulocytopenia and (3)
      mucosal damage. The site of infection is often unidentified. Two special sites,
      the oral cavity and central venous catheter, should not be overlooked. The
      infection is usually treated by empiric therapy. G-CSF is effective for rapid
      granulocyte recovery. For prophylaxis, the laminar air flow room, oral
      nonabsorbable antibiotics, and systemic chemoprevention with colonization
      resistance are recommended. Noteworthy among recent infections are (1) MRSA
      infection caused by long-term use of third generation cephems and (2) neutropenic
      enterocolitis, for which the most recommended aid is surgical resection of the
      lesion.

PMID- 7510349
TI  - Tenascin is an important component of the glomerular extracellular matrix in
      normal and pathologic conditions.
AB  - Tenascin (TN), a large oligomeric glycoprotein, is a recently described component
      of the extracellular matrix (ECM). Previous reports focusing largely on the role
      of TN in nephrogenesis have documented the strong expression of TN in embryonic
      kidney tissue and implied an important role for TN in nephrogenesis. However, the
      expression of TN in normal and pathologic kidneys in adults has not been
      systematically evaluated. In this study immunohistochemical staining for TN was
      applied to 184 renal specimens diagnosed as: normal kidney (23 cases); minimal
      change disease and its variants (8); mesangial proliferative glomerulonephritis
      (GN) including IgA nephropathy and mesangial proliferative lupus nephritis (9);
      endocapillary proliferative GN including membranoproliferative GN, lupus
      nephritis, and post-infectious GN (25); crescentic GN (11); membranous GN (19);
      focal segmental sclerosis (15); thrombotic microangiopathy (8); amyloidosis (5);
      diabetic nephropathy (9); primary tubulointerstitial nephritis (14); transplant
      rejection (14); and ischemia (24). It was found that: (a) there was unequivocal
      global diffuse staining limited to the mesangium in normal kidney; (b) regardless
      of the etiologies and the morphologic types of glomerular disease, whenever there
      was expansion of the ECM, whether in the mesangial, endocapillary, or
      extracapillary spaces, there was a concomitant and proportional in situ increase
      in the TN staining; (c) globally sclerotic glomeruli, regardless of causes,
      showed diffuse, strong staining, especially in the subcapsular fibrous deposition
      seen in ischemic sclerosis; (d) non-sclerotic glomeruli showing early ischemic
      change uniformly displayed a marked decrease or complete loss of staining; (e) in
      cases of thrombotic microangiopathy, there was segmental or global staining of
      the capillary wall, probably corresponding to the enlarged lamina rara interna;
      (f) all nodular lesions in diabetic glomerulosclerosis showed strong staining,
      but in several of them this staining was much more pronounced in the periphery
      than in the center of the lesion. Our study proves that TN is probably a
      component of the normal mesangial matrix, that TN is an ubiquitous component of
      the expanded glomerular ECM in pathologic conditions regardless of morphologic
      subtypes, and that further studies on the cell types and mechanisms responsible
      for TN synthesis may provide a new venue for the understanding of the process of
      glomerular sclerosis.

PMID- 7510348
TI  - [Studies on growth of brown adipose tissue by means of cell culture and
      angiogenesis in vitro techniques].
AB  - To elucidate the mechanism of brown adipose tissue (BAT) enlargement, we
      investigated the effects of norepinephrine (NE) and insulin on the in vitro
      growth of rat brown adipose cells (RBAC) and the capillary growth in angiogenesis
      in vitro using co-culture of bovine capillary endothelial cells (BCEC) and rat
      smooth muscle cells. In the primary cell culture, NE significantly enhanced the
      growth of RBAC in the range of 10(-9)-10(-5)M, whereas it did not stimulate the
      growth of BCEC. Insulin showed the same trend. Moreover, both NE and insulin
      appeared to increase the expression of mRNA for basic fibroblast growth factor
      (bFGF), which is a potent angiogenic factor, in RBAC. At 4 h after NE
      stimulation, the bFGF mRNA expression was considerably increased but it decreased
      markedly after 16 h. These results suggest that the bFGF mRNA expression in RBAC
      is quickly simulated by NE, wih resulting bFGF production. Actually, bFGF
      stimulated the RBAC growth up to about 170% of the control level. However,
      neither NE nor insulin stimulated the expression of the bFGF gene in BCEC. On the
      other hand, NE notably increased the capillary growth in vitro compared with
      insulin. It is thus possible that NE and insulin contribute to the growth of RBAC
      and endothelial cells partly through bFGF production by an autocrine mechanism,
      suggesting that both agonists play an important role not only in the thermogenic
      function of BAT but also in BAT enlargement.

PMID- 7510350
TI  - The impact of hepatitis C virus infection on renal allograft recipients.
AB  - A second generation hepatitis C virus recombinant immunoblot assay (RIBA) was
      used to screen stored perioperative serum from 641 renal allograft recipients.
      One hundred and nine (17%) were anti-HCV positive at the time of transplant. RIBA
      positivity was found to be an independent predictor of post-transplant liver
      disease in a logistic regression model (P < 0.05). Moreover, RIBA positive
      patients were at greater risk for infectious events (P = 0.03) and rejection
      episodes (P = 0.002). The cumulative dose of antilymphoblast globulin
      administered as induction therapy was an independent predictor of post-transplant
      liver disease in a dose response relationship. Qualitative PCR showed that 74% of
      the perioperative RIBA positive patients had detectable HCV RNA in a current
      serum sample. Further, quantitative HCV RNA analysis with a competitive template
      PCR and HCV strain identification by restriction fragment length polymorphism
      demonstrated a large range of HCV RNA copies/ml of serum and three different HCV
      strains (BK, Hutch and HCV-1). Neither quantity of HCV RNA nor strain type
      correlated with abnormal transaminases post-transplant. As yet, there has not
      been an effect of anti-HCV status on actuarial patient and graft survival. This
      study suggests that anti-HCV is not a contraindication to renal transplantation;
      however, we would recommend that the pre-transplant evaluation of the anti-HCV
      positive patient include a liver biopsy to properly stage the disease. Close post
      transplant follow-up is required in view of the increased risk for infection and
      rejection.

PMID- 7510351
TI  - Aprotinin does not decrease early graft patency after coronary artery bypass
      grafting despite reducing postoperative bleeding and use of donated blood.
AB  - Forty-five male patients with planned coronary artery bypass operation were
      randomized in a double blind fashion to receive either 6 million kallikrein
      inactivator units of aprotinin (high-dose group), 2 million kallikrein
      inactivator units of aprotinin (low-dose group), or placebo (control group).
      Postoperative bleeding was significantly decreased in both aprotinin groups in
      comparison to that in the control group (590 ml [290 to 1800 ml] high-dose group
      and 650 ml [280 to 1900 ml] low-dose group versus 920 ml (350 to 2700 ml) control
      group, p < 0.001). There was no difference between the two aprotinin groups. The
      need for postoperative blood transfusion was significantly lower in the aprotinin
      groups (1.46 [0 to 4] blood units high-dose group and 1.65 [0 to 5] blood units
      low-dose group versus 2.43 [0 to 7] blood units control group, p < 0.05). All
      patients underwent coronary angiography between the seventh and twelfth
      postoperative day. No difference was found among the three groups in patency of
      vein grafts-93.8% in the high-dose group, 94.5% in the low-dose groups, and 93.3%
      in the control group. Therefore, aprotinin significantly reduced postoperative
      bleeding and transfusion requirement after coronary artery bypass grafting
      without influencing early graft patency.

PMID- 7510352
TI  - Improving results with first-stage palliation for hypoplastic left heart
      syndrome.
AB  - Between January 1990 and February 1993, 73 patients underwent first-stage
      reconstruction for hypoplastic left heart syndrome at the University of Michigan
      Medical Center. During this period, surgical reconstruction remained essentially
      constant and consisted of a pulmonary artery-to-aorta anastomosis with allograft
      augmentation of the ascending, transverse, and proximal descending aorta,
      restriction of pulmonary blood flow with a polytetrafluoroethylene shunt from the
      innominate artery to the central pulmonary artery confluence, and atrial
      septectomy. Hospital survival was 62 of 73 patients, 85% (70% confidence limits:
      80% to 89%). These results stand in marked contrast to those obtained during the
      earlier years of our experience from 1986 to 1989 when only 21 of 50 patients
      (42%, 70% confidence limits: 35% to 49%) survived (p = 0.001). Among the most
      recent group of patients, only 2 of 7 patients older than 1 month of age at
      operation survived, whereas 60 of 66 (91%, 70% confidence limits: 87% to 94%)
      patients younger than 1 month of age survived (p = 0.0001). Anatomic subtype and
      ascending aortic diameter were not predictive of survival. Actuarial survivals
      for those patients younger than 1 month of age at the first-stage operation,
      including hospital deaths and subsequent operative procedures, were 81%, 74%, and
      74% at 6 months, 1 year, and 2 years, respectively. These results indicate that
      survival for patients after first-stage reconstruction for hypoplastic left heart
      syndrome has significantly improved in recent years. Older age was a strong risk
      factor, with a hospital survival of 91% for those patients undergoing first-stage
      palliation within the first month of life. These data have important implications
      for the type of operative intervention and its timing.

PMID- 7510354
TI  - Effect of combination therapy with all-trans-retinoic acid and recombinant human
      granulocyte colony-stimulating factor in patients with myelodysplastic syndromes.
AB  - Since all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G
      CSF) not only enhance proliferation and differentiation of normal myeloid cells
      but also synergistically promote the differentiation of myeloid leukemic blast
      cells in vitro, we have started a pilot study of combined treatment with ATRA and
      G-CSF in patients with myelodysplastic syndrome, to analyze the effect of these
      drugs on hematopoietic differentiation. ATRA was given at 45 mg/m2/day p.o. from
      week 1-12 and G-CSF at 5 micrograms/kg/day s.c. from week 5-12 with dose
      modifications according to the absolute neutrophil counts (ANC). A total of 15
      patients, predominantly with refractory anemia, were treated. During initial ATRA
      therapy, a bilineage response with increases of both ANC and platelet counts
      occurred in three patients. During combined ATRA/G-CSF therapy, ANC increased in
      all patients, and platelets increased in three out of 14 evaluable patients. An
      increase in hemoglobin concentration and a decrease in transfusion requirements
      occurred in one patient each. In the bone marrow, the myeloid-to-erythroid ratio
      increased during ATRA treatment and remained increased during concomitant G-CSF
      administration, while the maturation index of myeloid cells increased only in
      response to ATRA therapy, but returned to baseline during ATRA/G-CSF treatment.
      Cytogenetic analysis demonstrated persistence of the abnormal clones in all
      patients. The number of circulating progenitor cells CFU-GM increased in all
      patients studied. Serum concentrations of the soluble TNF receptor and IL-2
      receptor both increased, while TNF-alpha--already elevated prior to therapy--and
      soluble ICAM-1 concentrations did not significantly change. Adverse effects
      included dermatitis and cheilosis in most patients, and a drop in platelet counts
      related to G-CSF in one patient. The pilot study demonstrates that the
      combination treatment with ATRA/G-CSF is well tolerated, leading to normalization
      of ANC in most, and improvement of platelets and red blood cells in a subgroup of
      patients.

PMID- 7510353
TI  - Endotracheal balloon dilatation and self-expanding stent (Wallstent) for
      inoperable tracheomalacia.

PMID- 7510355
TI  - T-cell receptor J beta I/J beta II locus rearrangements concurring with a complex
      chromosomal aberration in an HTLV-1 positive T-cell lymphoma.
AB  - Human T-lymphotropic virus type I (HTLV-1) integration has been associated with
      the development of adult T-cell leukemia/lymphoma (ATL). Recently, a correlation
      between T-cell receptor (TCR) gene rearrangements and chromosomal aberrations has
      been implicated in this leukemia. We present a case of HTLV-1 infected adult T
      cell lymphoma that initially presented with a normal karyotype and germline J
      beta I/J beta II loci. As the disease evolved to the aggressive stage, a complex
      chromosomal rearrangement with a duplication of chromosome 6p23-->pter
      translocated to a derivative chromosome 16, was identified by molecular
      cytogenetic techniques. The nature of this complex abnormality would have been
      difficult to determine if only conventional banding techniques were performed.
      Rearrangement involving one J beta allele was also detected at that time. After
      initiation of chemotherapy, no germline J beta loci were detected, suggesting a
      possible second rearrangement involving this locus that was homologous. Although
      no known immune response genes are located at the breakpoints involved in this
      abnormality, the chromosomal aberration concurred with the initial J beta
      rearrangement.

PMID- 7510356
TI  - Additive effects of steel factor and antisense TGF-beta 1 oligodeoxynucleotide on
      CD34+ hematopoietic progenitor cells.
AB  - We previously demonstrated that TGF-beta 1 antisense oligodeoxynucleotides can
      release early CD34+ bone marrow progenitors from quiescence, and increase the
      numbers of mixed and large erythroid colonies. As Steel Factor (SF) has a similar
      effect on colony formation by CD34+ cells, we tested whether this factor acts by
      blocking the inhibitory effects of TGF-beta. That this is not generally the case
      was demonstrated by the finding that the combination of TGF-beta 1 antisense with
      SF in cultures of CD34+ bone marrow cells yielded enhanced colony formation that
      was more than additive when compared to cultures containing the single agents.
      This combination also yielded enhanced colony formation by CD34+ umbilical cord
      blood cells, but in this case, the effect was slightly less than additive. Thus
      in cord blood, some, but not all, of the progenitors that are maintained in
      quiescence by TGF-beta can be triggered into cycle by SF. However, the absolute
      number of CFU-GEMMs found in the antisense TGF-beta plus SF cultures of cord
      blood was 4-fold higher than that found in comparable bone marrow cultures. These
      data correlate well with our previous observations that umbilical cord blood
      contains 4-fold more CD34+ CD38- cells, the population found to respond to TGF
      beta 1 antisense oligodeoxynucleotides.

PMID- 7510357
TI  - The detection of colony-stimulating factors and steel factor in adherent layers
      of human long-term marrow cultures using reverse-transcriptase polymerase chain
      reaction.
AB  - In human long-term marrow cultures granulomonopoiesis is maintained for several
      weeks. Studies on granulomonocytic progenitors (CFU-GM) and their progeny have
      shown that survival, proliferation, differentiation and maturation of these cells
      are controlled by a set of glycoproteins, the colony-stimulating factors (CSFs)
      and the Steel factor. We have studied the expression of these factors using
      reverse transcriptase polymerase chain reaction (RT-PCR) in 17 adherent layers of
      normal bone marrow at 3, 5 or 7 weeks of culture. We have taken the 5637 bladder
      carcinoma cell line as a control for expression of GM-CSF, M-CSF, G-CSF and Steel
      factor, and PHA-activated T lymphocytes as a control for expression of multi-CSF
      (interleukin 3, IL-3). We have found that GM-CSF was expressed in the 17 adherent
      layers without induction by interleukin 1 beta (IL-1 beta). M-CSF was also
      detected in all cases, but in two early-stage (week 3 and week 5) cultures only
      after stimulation by IL-1 beta. G-CSF was detected in only 11 cases (three
      without IL-1 beta, and eight after addition of IL-1 beta). Steel factor was
      detected in 14 cases (ten without IL-1 beta, and four after addition of IL-1
      beta). IL-3 was not detected even by means of nested RT-PCR. These data indicate
      in six late-stage (week 5 or week 7) cultures G-CSF messenger concentrations
      10(3)-fold less than in 5637 control cells (for an identical amount of total
      cellular RNA). A similar conclusion may be drawn for Steel factor in three late
      stage cultures. For IL-3 our negative results indicate a messenger concentration
      10(5)-fold less than in activated T lymphocytes. These results suggest a crucial
      role for GM-CSF and M-CSF in the maintenance of granulomonopoiesis in human long
      term cultures. The role of G-CSF and Steel factor may be more marginal.
      Eventually IL-2 may not be involved in the regulatory process.

PMID- 7510358
TI  - Angiogenic factors are hematopoietic growth factors and vice versa.
AB  - Angiogenic factors are potent growth factors promoting proliferation and
      differentiation of vascular endothelial cells. Recent evidence suggest that these
      factors also promote hematopoietic cell growth. The major group of angiogenic
      growth factors is the fibroblast growth factor (FGF) family. Two prototypes,
      acidic FGF and basic FGF, have been demonstrated to interact with granulopoiesis
      and megakaryocytopoiesis. Basic FGF stimulates granulopoiesis in long term bone
      marrow cultures while acidic and basic FGF promote megakaryocytopoiesis. These
      effects are presumably mediated via specific FGF receptors, that have been
      identified in bone marrow and leukemia cell lines. Besides the FGF family,
      angiogenic inhibitors such as platelet factor-4 (PF-4) have been found to exhibit
      an inhibitory effect on megakaryocytopoiesis. In contrast, it has been
      demonstrated that hematopoietic growth factors including granulocyte-macrophage
      colony-stimulating factor (GM-CSF), or erythropoietin promote angiogenesis in
      vivo and in vitro. In light of these recent observations and the common origin of
      endothelial cells and hematopoietic cells, it is suggested that angiogenic
      factors are hematopoietic growth factors and vice versa. However, these data must
      be interpreted with caution and a careful in vivo evaluation should be done
      before these observed in vivo effects are proven to be significant to the
      physiopathology of hematopoiesis or angiogenesis.

PMID- 7510359
TI  - Acidic and basic FGF mRNA expression in the middle ear mucosa during experimental
      acute and chronic otitis media.
AB  - Fibroblast growth factors (FGFs) induce the proliferation and differentiation of
      cells of mesodermal and neuroectodermal origin. Using in situ hybridization,
      messenger ribonucleic acid encoding acidic FGF, basic FGF and FGF receptor 1
      (FGFR1) were localized in the middle ear mucosa of experimental animals with
      acute and chronic immune-mediated otitis media with effusion (OME). Basic FGF
      labeled cells were seen in the subepithelial connective tissue layer (SE)
      preferentially near the epithelial basement membrane. Acidic FGF-labeled cells
      were seen in the SE, preferentially near blood vessels and occasionally in the
      cellular middle ear effusion (CE). FGFR1-labeled cells were seen in the SE and in
      the CE. The distribution of labeled cells in the middle ear suggests that basic
      FGF is produced by fibroblasts, acidic FGF is produced by leukocytes, and FGFR1
      is produced by both fibroblasts and leukocytes. A role is proposed for these
      peptides in the proliferation and maintenance of the middle ear submucosa during
      otitis media.

PMID- 7510360
TI  - [Nocturnal ventricular arrhythmia in patients with sleep apnea and suspected
      coronary heart disease].
AB  - BACKGROUND: Patients with sleep apnea and nocturnal brady- and tachyarrhythmia
      are considered to be patients at especially high risk within the group of all
      apnea patients. PATIENTS AND METHODS: 13 patients with sleep apnea (apnea-index >
      10 events/h), suspected coronary heart disease and known increased frequency of
      nocturnal premature ventricular contractions (PVC) were studied. Polysomnography,
      long-term ECG and six-lead ECG were performed. RESULTS: Within the period studied
      (1.00 to 6.00 o'clock), an average of 47 PVC per hour was recorded (range 4 to
      337/h). In two patients 24 episodes of nocturnal myocardial ischemia were
      observed, but were not accompanied by PVC. Interestingly only 387 of 1371
      premature ventricular contractions (28.2%) were associated to
      apnea/hyperventilation episodes. Arrhythmia occurred mainly during sleep stages
      I/II and REM (n.s.). There was a tendency towards more frequent PVC with more
      pronounced oxygen desaturations. CONCLUSION: Patients with coronary heart
      disease, obstructive sleep apnea and severe hyoxemia are at higher risk of
      developing nocturnal PVC because reduced hypoxic tolerance of the heart may lead
      to electrical instability.

PMID- 7510362
TI  - DNA-damaging agents stimulate the formation of directed reciprocal translocations
      in Saccharomyces cerevisiae.
AB  - DNA-damaging agents can stimulate the formation of directed reciprocal
      translocations in strains of Saccharomyces cerevisiae containing his3
      recombinational substrates to generate chromosomal rearrangements. Such agents
      were compared with those that can stimulate sister-chromatid recombination. We
      show that chemicals and environmental agents that produce a variety of DNA
      lesions, including bulky adduct, thymidine dimers, interstrand cross-links,
      double-strand breaks alkylated bases, can stimulate recombination to yield
      reciprocal translocations. Of the agents tested, only the alkylating agents
      methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG),
      and a bifunctional agent that causes bulky DNA adducts, 4-nitroquinoline-N-oxide
      (4-NQO), significantly stimulate sister-chromatid recombination in our assay.
      Factors that contribute to the stimulation of interchromosomal recombination
      include strain genetic background and ploidy.

PMID- 7510363
TI  - Radiation hypersensitivity of LEC strain rats controlled by a single autosomal
      recessive gene.
AB  - LEC strain rats (LEC rats), which are known to develop hereditarily spontaneous
      fulminant hepatitis 4-5 months after birth, were highly sensitive to whole-body X
      irradiation when compared to WKAH strain rats. The radiosensitivity of F1 hybrids
      of LEC and WKAH rats was similar to that of WKAH rats and significantly lower
      than that of LEC rats. Segregation data of backcross hybrids (F1 x LEC and LEC x
      F1) suggested that the hypersensitivity of LEC rats to whole-body irradiation is
      controlled by a single autosomal recessive gene. The radiosensitivity of
      fibroblasts from LEC rats was higher than that of fibroblasts from WKAH rats. The
      repair process of DNA double-strand breaks in LEC cells was slower than that in
      WKAH cells. LEC rats could provide a useful animal model to assist in
      understanding the mechanism of radiation-induced DNA damage and repair.

PMID- 7510361
TI  - Mutagenic response and repair of cis-DDP-induced DNA cross-links in the Chinese
      hamster V79 cell mutant V-H4 which is homologous to Fanconi anemia (group A).
AB  - Previously, it has been shown that the V-H4 mutant of Chinese hamster V79 cells
      is homologous to Fanconi anemia (FA) group A cells. This hamster cell mutant
      shows a specific sensitivity to DNA cross-linking agents; therefore, the
      induction and repair of DNA cross-links were studied in V-H4 and wild-type V79
      cells after cis-DDP treatment by the DNA alkaline elution technique. A
      significant difference in repair of these lesions in V-H4 and wild-type cells was
      observed. After the cis-DDP treatment (24 h) about 3 times more cross-links
      remained in V-H4 cells in comparison to the parental V79 cells. These results
      indicate that the process of cross-link repair in V-H4 cells is hampered when
      compared to that of wild-type cells. To assess the effect of slower removal of
      DNA cross-links on the mutability of V-H4, the induction of mutants at the
      hypoxanthine-guanine phosphoribosyltransferase locus (HPRT) by cis-DDP was
      studied in V-H4 and V79 cells. Despite the increased cytotoxicity of cis-DDP to V
      H4 cells, the mutation induction at the HPRT locus was not significantly
      different in both cell lines, but when the frequency of the hprt mutants was
      plotted against survival, hypomutability was observed in V-H4 cells after the cis
      DDP treatment.

PMID- 7510364
TI  - Increased DNA-repair capacity and the modulation of 2 proteins in and
      metallothionein overexpressing Chinese hamster cell line.
AB  - Elevated intracellular levels of metallothionein have been associated with
      resistance to the cytotoxic effects of some alkylating agents. In order to study
      the mechanisms responsible for this resistance, we used a pair of CHO cell lines
      consisting of normal K1-2 cells and their derivative K1-2MT, which overexpresses
      the human metallothionein II-A gene (Lohrer et al., 1989). K1-2MT cells were
      found to be resistant to cadmium chloride and the alkylating agents N-methyl-N'
      nitro-N- nitrosoguanidine (MNNG), but resistance did not extend to the alkylating
      agent, 1,3-bis(2-chloroethyl)- 1-nitrosourea, nor to adriamycin, an inhibitor of
      DNA synthesis. The DNA damage caused by MNNG, was only marginally less in
      resistant cells compared with the parental cell line, thus excluding drug
      scavenging as a possible mechanism for resistance. Also, glutathione S
      transferases (GSTs) were present at equal levels in both cell lines (acidic and
      basic type GST) or slightly reduced in drug resistant K1-2MT cells (neutral type
      GST), thereby ruling out metabolic inactivation of the alkylating agents.
      However, the drug resistant phenotype was accompanied by a more efficient block
      of DNA synthesis after MNNG treatment and by a 3-h delay in the G2 phase of the
      cell cycle. Using two-dimensional gel electrophoresis of total protein extracts,
      we identified a 24-kDa protein (MIP1), which is only present in the resistant K1
      2MT cells, and a 23.5-kDa protein (MIP2) which is 2-3 times over-synthesized in
      K1-2MT cells. MNNG treatment reduced the level of both proteins MIP1 and MIP2.
      These results suggest that the proteins MIP1 and possibly MIP2 may be responsible
      for the alkylating agent resistant phenotype and are probably modulated by the
      human metallothionein II-A protein.

PMID- 7510365
TI  - Molecular analysis of the XP-D gene in Italian families with patients affected by
      trichothiodystrophy and xeroderma pigmentosum group D.
AB  - In several patients with the rare hereditary disorder trichothiodystrophy (TTD),
      a DNA repair defect has been shown to be in the same gene as in xeroderma
      pigmentosum complementation group D (XP-D). The ERCC-2 gene (excision repair
      cross-complementing rodent repair deficiency of group 2) has recently been
      identified as a strong candidate gene for XP-D, since it restores normal UV
      sensitivity to XP-D cells after transfection. Using Southern blotting, we have
      analysed the ERCC-2 gene in DNA samples from 28 members of nine Italian families
      with individuals affected by XP-D (three patients) or by TTD with
      photosensitivity due to the XP-D defect (eight patients). No major modifications
      of the ERCC-2 gene were detected with two cDNA probes in either XP-D or TTD
      patients indicating that the association between TTD and XP-D is not likely to
      result from a large deletion or rearrangement involving this gene. We found two
      RFLPs after digestion of the DNA samples with TaqI or MspI, but neither of them
      could be related to the molecular alteration determining the pathological
      phenotype. We also analysed a human homologue detected with the hamster sequence
      isolated by Arrand et al. (1989), which specifically, but partially, complements
      the DNA repair deficiency in XP-D cells. Our analysis demonstrated that this gene
      is not the primary gene defective in XP-D. In fact two RFLPs detected with a
      genomic probe do not co-segregate with the disease in an XP-D family.

PMID- 7510367
TI  - Altered DNA ligase III activity in the CHO EM9 mutant.
AB  - Delayed joining of DNA strand breaks and a high spontaneous level of sister
      chromatid exchanges (SCEs) are characteristics of the mutant cell strain EM9 of
      Chinese hamster ovary (CHO) cells. The introduction of the human gene XRCC1 into
      EM9 cells reverts the phenotypic properties of EM9 to those of the wild type. We
      have investigated both DNA ligase activities and a protein which stimulates DNA
      ligase activity in mutant EM9 cells, XRCC1-transfectant H9T3-7-1 cells and wild
      type AA8 cells. Our results, which demonstrate both a decreased DNA ligase
      activity in EM9 cells using poly(rA).oligo(dT) as substrate and a decreased
      ability of DNA ligase III to form a covalent DNA ligase III-adenylate
      intermediate with AMP, clearly indicate an altered DNA ligase III activity in the
      mutant. Furthermore, the AMP-binding capacity of DNA ligase III and its enzymatic
      activity with the synthetic polymer were restored after transfection of EM9 with
      the human XRCC1 gene. Immunoblotting data suggest that the XRCC1 gene does not
      code for DNA ligase III. In conclusion, the data indicate that the EM9 cell
      strain has an altered DNA ligase III activity that can be restored by the XRCC1
      gene product.

PMID- 7510366
TI  - An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma
      pigmentosum.
AB  - We have isolated a human excision repair gene ERCC5 which complements the defect
      of the mouse UV-sensitive mutant XL216 (rodent complementation group 5). Here we
      report cDNA cloning of human and mouse ERCC5 genes using an exon containing an
      ERCC5 fragment as a probe. The ERCC5 cDNA encodes a predicted 133-kDa nuclear
      protein that shares some homology with the product of the yeast DNA repair gene
      RAD2. Transfection with mouse ERCC5 cDNA restored normal levels of UV resistance
      to XL216 cells. Microinjection of ERCC5 cDNA specifically restored the defect of
      xeroderma pigmentosum group G cells (XP-G) as measured by unscheduled DNA
      synthesis, and XP-G cells stably transformed with ERCC5 cDNA showed nearly normal
      UV resistance.

PMID- 7510368
TI  - Differential repair of UV damage in a developmentally regulated gene of
      Dictyostelium discoideum.
AB  - The repair of cyclobutane pyrimidine dimers was measured under non-replicating
      conditions in a 2054-bp fragment of a cAMP-inducible cysteine proteinase (CP2)
      gene in D. discoideum. Overall genomic repair was unaffected by cAMP. The removal
      of dimers from CP2 in the wild-type NP2 cells as quantified using T4 endonuclease
      V was independent of transcription and was the same as in the overall genome. In
      a UV-sensitive radC mutant in which the rate of overall dimer removal was
      previously shown to be reduced, the initial rate of dimer removal in the
      uninduced CP2 gene (-cAMP) was 3-fold lower compared to the induced gene (+cAMP),
      in which repair was identical to that for the induced and uninduced states of
      NP2. D. discoideum may have two pathways for repairing dimers. One, effective in
      the wild-type strain but of reduced efficiency in radC repairs dimers equally
      well independent of transcription and at about the same rate as in the overall
      genome. A second pathway, retained in radC, repairs dimers more slowly in the
      overall genome and in the uninduced CP2 gene while undergoing the wild-type rate
      of repair in the transcriptionally active gene. Hence radC has reduced ability to
      repair transcriptionally inactive DNA, a defect similar to that of xeroderma
      pigmentosum group C.

PMID- 7510369
TI  - On the quantitative relationship between O6-methylguanine residues in genomic DNA
      and production of sister-chromatid exchanges, mutations and lethal events in a
      Mer- human tumor cell line.
AB  - O6-Methylguanine (m6G) is an altered base produced in DNA by SN1 methylating
      agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). This lesion is
      repaired by the protein O6-methylguanine-DNA methyltransferase (MGMT) in normal
      human cell lines, but is not repaired in certain human tumor lines that are
      termed Mex- or Mer-. Compared with repair-proficient cell lines, such repair
      deficient tumor lines are hypersensitive to the production by MNNG of sister
      chromatid exchanges (SCE), mutations and lethality. We report here that MNNG
      treatment produces 1 SCE for every 42 +/- 10 m6G formed in the genome of Mer-
      tumor cells, 1 6TG-resistant mutant for every 8 (range of 5-14) m6G produced
      statistically in the coding region of the hypoxanthine phosphoribosyltransferase
      gene, and 1 lethal event per 6650 +/- 1200 m6G. In addition, in vitro base
      mismatch incision at m6G: BrU pairs was similar to that at m6G: T pairs, the
      lesions that likely initiate SCE production. We conclude that m6G residues in
      genomic DNA are very recombinogenic as well as highly mutagenic in Mer- human
      tumor cells. The results are interpreted in terms of the relationship between
      methylation-induced SCE and G: T mismatch recognition.

PMID- 7510370
TI  - Gonadotropin-releasing hormone modifies action potential generation in sheep pars
      distalis gonadotropes.
AB  - Cell-intact patch-clamp recording was used to determine the electrophysiological
      responses of sheep anterior pituitary gonadotropes to stimulation with
      gonadotropin-releasing hormone (GnRH). Cells were identified prior to recording
      by reverse haemolytic plaque assay (RHPA), or using morphological criteria in
      preparations enriched in gonadotropes by Percoll density gradient centrifugation.
      Most cells identified by RHPA did not generate action potentials, and responses
      to GnRH were inconsistent. The majority of gonadotropes in enriched preparations
      however spontaneously generated action potentials requiring the entry of both
      extracellular Na+ and Ca2+, and involving tetraethylammonium-sensitive K+
      channels. Two-minute GnRH application (10(-7) M) evoked a characteristic sequence
      of changes in action potential generation. The immediate response was an
      inhibition of action potentials, followed by a recovery of these events, with a
      progressive decline in amplitude over about 10 min. The cells then remained
      quiescent for up to 1 h. The results indicate that GnRH may evoke an initial
      hyperpolarization involving Ca(2+)-dependent K+ channels, followed by a sustained
      depolarizing response, with consequent inactivation of action potential
      generation.

PMID- 7510371
TI  - Effects of prostacyclin analogue iloprost on the regional cerebral blood flow in
      transplanted rat brain tumour.
AB  - We studied the effect of intracarotid administration of prostacyclin analogue
      iloprost on the regional cerebral blood flow in transplanted rat C6 glioma by the
      hydrogen clearance method. Iloprost at doses of 0.1 and 0.5 micrograms/kg/min
      produced a selective increase of the regional cerebral blood flow in the tumour
      (17.8 +/- 5.6%, p < 0.05 and 27.3 +/- 10.3%, p < 0.05, respectively) without
      significant change of the regional cerebral blood flow in the ipsilateral
      hemisphere and the systemic arterial pressure. At a dose of 1 microgram/kg/min,
      iloprost produced a significant reduction of a systemic blood pressure, but did
      not change the regional cerebral blood flow significantly both in the tumour and
      the ipsilateral hemisphere. These results indicated that brain tumour vessels
      could respond to iloprost in a different fashion from the normal brain
      capillaries. The selective action of iloprost to the tumour vessels might
      contribute to the drug-delivery in malignant brain tumour.

PMID- 7510372
TI  - Neural mediation of the cardiovascular responses to intrathecal administration of
      substance P in the rat: slowing of the cardioacceleration by an adrenal opioid
      factor.
AB  - Substance P, given intrathecally at the second (T2) or ninth (T9) thoracic level
      in the anesthetized rat, increased heart rate, arterial pressure and circulating
      catecholamines. At T9 in adrenalectomized animals and at T2 in intact animals,
      the cardioacceleration was more abrupt than in intact animals injected at T9
      suggesting that the adrenals are not necessary for the cardiovascular responses
      and that the adrenals may have released a factor which slows the neurally
      mediated cardioacceleration. As opioids are co-released with catecholamines from
      the adrenals, naloxone (10 mg/kg i.v.) or nalorphine HCl (which does not cross
      the blood-brain barrier; 10 mg/kg s.c.) was given 5 min before administration of
      substance P at T9 in intact rats. In both groups the cardioacceleration was
      similar to that elicited in adrenalectomized animals, indicating that the adrenal
      factor was opioid and that its action was peripheral rather than central. When
      propranolol (10 mg/kg i.v.) was given 3 or 15 min before, substance P increased
      arterial pressure but heart rate was unchanged, indicating that the opioid factor
      was not slowing the cardioacceleration by a direct effect on the heart. The
      results indicate that intrathecal administration of substance P produces a
      neurally mediated increase in arterial pressure and heart rate and induces the
      release of an adrenal opioid factor which slows the neurally-mediated
      cardioacceleration by an action in the periphery. This indicates a functional
      interaction between humoral and neural sympathetic mechanisms regulating the
      cardiovascular system.

PMID- 7510374
TI  - Inducible nitric oxide synthase in glial cells.
AB  - Nitric oxide (NO), a free radical gas, has been suggested to mediate both
      synaptic plasticity and neuronal death. NO is generated by constitutive and
      inducible types of NO synthase (cNOS and iNOS, respectively). The neuronal cNOS
      was recently cloned, sequenced and characterized. In contrast, properties of iNOS
      in the brain are not fully understood. It is noted that glial cells can form NO
      and that microglial and reactive astroglial cells are accumulated around
      neurodegenerative sites in the brain, suggesting a relationship between neuronal
      injury and NO originated from glial cells. We found that several stimuli such as
      endotoxin (lipopolysaccharide) and cytokines induced iNOS in glial cells of rat
      brain. This article reviews recent findings on characteristics and the induction
      mechanism of iNOS in the glial cells, and discusses the possible
      pathophysiological functions of iNOS in the brain.

PMID- 7510373
TI  - [Value of continuous electrocardiographic monitoring of patients with syncope.
      Results of a prospective study].
AB  - AIM: Syncope, a temporary loss of conscience, is a frequent cause for consulting
      the family doctor or more often being brought to the hospital emergency ward. In
      order to evaluate the importance of the continuous recording of ECG in the
      formulation of the diagnosis, the relevant data were extrapolated from more
      general data in the prospective study. MATERIAL: A total of 194 patients were
      enrolled whose diagnosis was divided into three distinct stages. Continuous
      echographic registration using Holter's method and/or bedside monitoring was
      included in the 2nd stage and was performed in 134 patients. RESULTS: 102 out of
      134 patients (76.11%) showed rhythm alterations: varying degrees of atrio
      ventricular block were recorded in 6 patients; supraventricular arrhythmia in 73
      cases which were divided according to a modified to a modified version of Lawn's
      classification. Continuous ECG recording alone proved decisive in formulating a
      diagnosis in 6 patients (one of which together with echocardiogram): in 2
      patients due to the presence of complex ventricular extrasystoles; in 4 due to
      torsion of the tip, sinusal arrest, cardiac arrest, supraventricular tachycardia
      with aberrant intraventricular conduction, respectively. CONCLUSIONS: Especially
      when standard surface ECG is carried out rapidly following an acute attack,
      continuous ECG recording is of scant diagnostic value due to the etiological
      definition of syncope. But due to its moderate cost and non-invasive character it
      is worth performing in syncopes of suspected cardiogenic etiology with a more
      severe prognosis.

PMID- 7510375
TI  - Expression of tenascin and BDNF during the migration and differentiation of
      grafted Purkinje and granule cells in the adult rat cerebellum.
AB  - It is believed that 'cell-adhesion molecules' and neurotrophic factors play
      important roles in the host-graft interactions during the reconstruction of
      injured brain by neural transplantation. In this study, we have examined the
      expression of such molecules and factors during the migration and differentiation
      of grafted Purkinje and granule cells in the adult rat cerebellum. Cerebellar
      primordium at the 14th gestational day (E14) was transplanted into adult rat
      cerebellum. Purkinje cells which had migrated from the grafted tissue into the
      host molecular layer were identified immunohistochemically with a specific
      marker, anti-spot 35 antibody, as well as by labeling them with bromodeoxyuridine
      (BrdU) during their final mitotic period. In the grafted site, transient
      expression of a neuron-glia cell adhesion molecule, tenascin, was detected
      immunohistochemically. This molecule was expressed transiently in the host tissue
      adjacent to the migratory Purkinje cells, as well as within the grafted tissue.
      Tenascin was not detected in intact host tissue apart from the grafted tissue. In
      the light of tenascin expression in the migratory process of Purkinje and granule
      cells during cerebellar development, the induction of this molecule in the host
      tissue might be involved in the migration of grafted Purkinje and granule cells.
      Furthermore, gene expression of brain-derived neurotrophic factor (BDNF) was
      found by in situ hybridization and the expression of NGF receptor was found
      immunohistochemically in the areas where grafted Purkinje and granule cells
      developed. These findings suggest the involvement of the neurotrophic factor in
      the growth and differentiation of the grafted cerebellar primordium.

PMID- 7510376
TI  - Fibroblast growth factor induces proliferating cell nuclear antigen
      immunoreactive cells in goldfish retina.
AB  - New rod photoreceptors are added to mature teleost retinas throughout life by
      regulated proliferation of rod precursor cells (RPCs). In this study, candidate
      regulators of RPC proliferation, acidic and basic fibroblast growth factors (aFGF
      and bFGF; 0.1 microgram/eye), interleukin-6 (IL-6; 0.1 microgram) and
      phytohaemagglutinin (HA15; 1.0 microgram), were injected intravitreally into one
      eye of goldfish (body length 5-6 cm), and mitotic RPCs in both retinas were
      detected and counted 3-50 days later by immunohistochemistry for proliferating
      cell nuclear antigen (PCNA). Retinal integrity after treatment was assessed by
      immunohistochemistry for tyrosine hydroxylase (TH) and other retinal antigens.
      All the agents applied altered the density of PCNA-immunoreactive (ir) cells in
      the outer and inner nuclear layers (ONL and INL) in both retinas as soon as 2-3
      days after unilateral injection. Initially (2-20 days after injection),
      particularly in the treated retina, PCNA-ir cells appeared in clusters
      accompanied by various numbers of scattered individual cells, but subsequently
      the clusters of PCNA-ir cells disappeared while the density of singly distributed
      cells increased until 30 days after injection. At the doses given, these effects
      were most striking with aFGF and bFGF and less with IL-6 and HA15. In radial
      cryosections, other cellular elements immunoreactive to markers such as TH,
      serotonin, neuropeptide Y, substance P, glutamine synthetase, glial fibrillary
      acidic protein and protein kinase C, were found normal in terms of morphology. In
      addition, a monoclonal antibody (NN-2) was found to label some non-neuronal
      structures (macrophages, microglia and blood vessels) inside and outside the
      retina intoxicated with 6-hydroxydopamine, a few NN-2-ir cells being PCNA
      positive. However, clustered PCNA-ir and marginal neuroblast cells were NN-2
      negative. These results indicate that FGFs may play an important role in
      stimulating the proliferation of RPCs, for example, in the regeneration of fish
      retinas following neurotoxic destruction.

PMID- 7510378
TI  - The reticulovestibular projection in the rabbit: an experimental study with the
      retrograde horseradish peroxidase method.
AB  - The reticulovestibular projections of the brainstem in the rabbit were studied by
      the retrograde transport of horseradish peroxidase (HRP). After selective
      iontophoretic injections of the tracer into various subdivisions of the
      vestibular nuclear complex (VNC), labeled neurons were found in defined regions
      of the reticular formation (RF) of the caudal pons and the rostral medulla. The
      results indicate that all four vestibular nuclei receive projection from RF. This
      projection is bilateral with a contralateral predominance. The major projection
      originates from dorsal and dorsolateral regions of the caudal pontine reticular
      nucleus (RPc) and the gigantocellular reticular nucleus (RGc) at the transitional
      level between them. A modest projection originates from pars alpha of the caudal
      pontine reticular nucleus (RPc alpha), the parvocellular reticular nucleus (Rpc)
      and pars alpha of the parvocellular nucleus (Rpc alpha), mostly from their
      ventral regions. A small projection arises from pars alpha of the gigantocellular
      reticular nucleus (RGc alpha), as well as from the ventral reticular subnucleus
      (Rv) and cell group a in the caudal aspect of the medulla. No clear-cut topical
      relationship was noted between the location of neurons in RF and projection site
      in VNC. The superior vestibular nucleus (SV) and the medial vestibular nucleus
      (MV) receive projections exclusively from RPc and RGc, whereas the lateral
      reticular nucleus (LV) and the inferior vestibular nucleus (IV) receive
      additional projections from the remaining RF nuclei. The termination areas of
      reticular fibers within SV and IV seem to be diffuse but in MV and LV there is a
      clear preponderance to the regions located ventrally. The present study has
      established cells of origin for the reticulovestibular projections from the
      pontomedullary RF to individual VNC nuclei in the rabbit.

PMID- 7510377
TI  - Extracellular levels of serotonin in the medial pontine reticular formation in
      relation to sleep-wake cycle in cats: a microdialysis study.
AB  - Extracellular levels of endogenous serotonin (5-hydroxytryptamine; 5-HT) and its
      major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were measured in the medial
      pontine reticular formation (medial PRF) of intact cats. A microdialysis probe
      was inserted through a guide cannula into the medial PRF. At least 12 h after the
      probe insertion, in vivo brain microdialysis was initiated. The perfusion rate
      was 1 microliters/min, and perfusate fractions at regular intervals of 20 min
      were collected. Changes in extracellular 5-HT levels were compared across sleep
      wake states of the animals, such as waking (W), slow wave sleep (SWS) and rapid
      eye movement (REM) sleep. To assess sleep-wake states, EEG, EMG, EOG and PGO
      waves were simultaneously recorded in parallel with microdialysis of the medial
      PRF. Extracellular 5-HT levels were highest (20-28 fmol/20 microliters) during W.
      As the animals entered SWS, 5-HT levels decreased to about 90% of those during W.
      The state of REM sleep usually interrupted SWS for 3-8 min. During the longer
      periods of REM sleep, during the 20 min periods in which the perfusates were
      collected, we observed the lowest 5-HT levels (60-50%).

PMID- 7510382
TI  - [Management of benign prostatic hypertrophy].

PMID- 7510380
TI  - Intraretinal leakage of indocyanine green dye.
AB  - PURPOSE: Indocyanine green (ICG) dye is known to remain selectively in and around
      choroidal neovascularization (CNV) associated with age-related macular
      degeneration, and is thought to be cleared from the overlying retinal circulation
      without leakage. This is the basis of ICG dye-enhanced laser photocoagulation.
      The authors have observed, however, leakage of ICG dye into cystoid spaces within
      the retinal and have determined the incidence, clinical features, and
      angiographic characteristics of this newly described phenomenon. METHODS: The
      digital ICG videoangiograms of 149 consecutive patients with exudative age
      related macular degeneration and occult CNV were reviewed independently to
      determine the characteristics of intraretinal ICG dye leakage. RESULTS: Of the
      149 patients with occult CNV, 16 (11%) demonstrated intraretinal leakage of ICG
      dye between 14 and 34 minutes (median = 20 minutes). The clinical features most
      commonly associated with this phenomenon are: subretinal fluid (88%), subretinal
      hemorrhage (88%), subretinal lipid (63%), and retinal pigment epithelial
      detachment (56%). CONCLUSIONS: Indocyanine green dye may not be as concentrated
      in and around CNV as previously reported. The delayed onset of its appearance
      within intraretinal cystoid spaces may suggest a diffusible choroidal source of
      leakage. Intraretinal ICG dye may be a relative contraindication for ICG dye
      enhanced laser photocoagulation.

PMID- 7510381
TI  - Did reflexive catalysts drive chemical evolution?
AB  - High-energy starting materials and energy sources on the primitive earth would
      have generated abundant and varied organic molecules of small or medium size. It
      is questionable, however, whether ordinary chemical evolution could have produced
      information-carrying polymers. The end point might have been a fixed steady state
      if some form of autocatalysis had not intervened. Autocatalytic synthesis is
      possible for small molecules as illustrated by the formose reaction, in which
      glycolaldehyde condenses with formaldehyde to form sugars, and resulting tetroses
      may cleave into two molecules of glycolaldehyde. This and other 'reflexive
      catalysts', some functioning in molecular aggregates, may have energized chemical
      evolution and carried it to a level at which RNA or an RNA analog could replicate
      itself.

PMID- 7510379
TI  - Involvement of NK1 receptors in synaptic transmission in the guinea pig coeliac
      ganglion.
AB  - Using intracellular recording techniques, we examined the effects of tachykinin
      receptor agonists and antagonists on electrophysiologically identified tonic
      neurons of the isolated guinea pig coeliac ganglion. In most of the tonic
      neurons, substance P (SP), neurokinin A (NKA) and/or senktide induced a
      depolarization. The effects of SP and NKA were blocked by the NK1-selective
      antagonist, GR71251 (5 microM), but not by the NK2-selective antagonist, L659,877
      (10 microM), whereas the effect of senktide was not affected by these
      antagonists. The NK1-selective agonists, [Sar9,Met(O)2(11)]SP and SP methyl
      ester, and the NK3-selective agonist, [MePhe7]neurokinin B, also evoked
      depolarizations in tonic neurons. By contrast, the NK2-selective agonists,
      [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, at 1 microM each, did not evoke
      any significant depolarizing response. Repetitive electrical stimulation of the
      mesenteric nerves induced slow excitatory postsynaptic potentials (EPSPs) in the
      majority of tonic neurons, which were depressed by GR71251 (5 microM). These
      results suggest that NK1 and NK3 receptors but not NK2 receptors are involved in
      the tachykinin-induced depolarization of tonic neurons, and that the NKA-induced
      response is due to the activation of NK1 receptors. This study also suggests the
      involvement of NK1 receptors in the slow EPSPs in tonic neurons.

PMID- 7510383
TI  - Cytokeratin subtyping in normal and neoplastic epithelium: basic principles and
      diagnostic applications.

PMID- 7510384
TI  - The diagnosis of melanoma: current approaches addressing tumor differentiation.

PMID- 7510385
TI  - Applications of immunohistochemistry to the diagnosis and prognostication of
      prostate carcinoma and prostatic intraepithelial neoplasia.

PMID- 7510386
TI  - Calcitonin and somatostatin containing C cells in rat and human thyroid.
      Immunohistochemical study by a double-staining method.
AB  - C cells of the thyroid probably exert a paracrine control on follicular cells
      through secretion of peptides such as calcitonin and somatostatin. The aim of the
      present study was to investigate the expression of different peptides produced by
      C cells in rat thyroid and in the different morphological and pathological
      conditions of the human thyroid. Therefore we employed the immunohistochemical
      double-staining method using anti-calcitonin and anti-somatostatin antibodies.
      The results of this study show the presence of C cells containing calcitonin and
      C cells containing somatostatin exclusively in the rat and the human thyroid.
      This distinction with prevalence of one peptide on the other is maintained in the
      different morphological and pathological conditions of the human thyroid.

PMID- 7510387
TI  - The existence of eukaryotic ribonucleoprotein consensus sequence-type RNA-binding
      proteins in a prokaryote, Synechococcus 6301.
AB  - A group of proteins containing a conserved ribonucleoprotein consensus sequence
      (RNP-CS)-type RNA-binding domain (CS-RBD) of approximately 80 amino acids is
      present in eukaryotic cells and binds specifically to a wide variety of RNA
      molecules. We have isolated 12 kDa single-stranded DNA binding proteins from the
      unicellular cyanobacterium Synechococcus 6301. The amino-terminal sequence was
      determined and two distinct genomic clones were isolated from a Synechococcus
      6301 genomic library. Sequence analysis revealed that two closely related
      proteins contain a single CS-RBD of 82 amino acids and are named as 12RNP1 and
      12RNP2. Both of the CS-RBDs share the highest amino acid identity with those of
      chloroplast ribonucleoproteins (40-51%). The 12RNP proteins were expressed in
      Escherichia coli bearing plasmids encoding glutathione S-transferase/12RNP fusion
      proteins and subjected to in vitro nucleic acid-binding assay. Both 12RNP1 and
      12RNP2 bind to RNA homopolymers poly(U) and poly(G), indicating that they might
      be RNA-binding proteins. This is the first example of such proteins in
      prokaryotes. The 12RNP1 and 12RNP2 genes are transcribed as monocistronic mRNAs
      and the steady-state mRNA level of 12RNP1 is over 20-fold than that of 12RNP2.
      Due to the easiness of genetic manipulations the cyanobacterium will provide an
      excellent system to analyze the function of not only cyanobacterial but also
      plant RNA-binding proteins.

PMID- 7510388
TI  - Mutagenicity and pausing of HIV reverse transcriptase during HIV plus-strand DNA
      synthesis.
AB  - The unusually high frequency of misincorporation by HIV-1 reverse transcriptase
      (HIV RT) is likely to be the major factor in the rapid accumulation of viral
      mutations in AIDS, especially in the env gene. To investigate the ability of HIV
      RT to copy the env gene, we subcloned an HIV env gene fragment into a single
      stranded DNA vector and measured the progression of synthesis by HIV RT. We
      observed that HIV RT, but not RT from avian myeloblastosis virus, DNA polymerase
      alpha or T7 DNA polymerase, pauses specifically at poly-deoxyadenosine stretches
      within the env gene. The frequency of bypassing the polyadenosine stretches by
      HIV RT is enhanced by increasing the ratio of enzyme to template. We measured the
      fidelity of DNA synthesis within a segment of the hypervariable region 1 of the
      env gene (V-1) containing a poly-deoxyadenosine sequence by repetitively copying
      the DNA by HIV RT, and then cloning and sequencing the copied fragments. We found
      that 27% of the errors identified in V-1 sequence were frameshift mutations
      opposite the poly-adenosine tract, a site where strong pausing was observed.
      Pausing of HIV RT at the polyadenosine tract could be enhanced by either
      distamycin A or netropsin, (A-T)-rich minor groove binding peptides. Moreover,
      netropsin increases the frequency of frameshift mutations in experiments in which
      HIV RT catalyzes gap filling synthesis within the lacZ gene in double-stranded
      circular M13mp2 DNA. These combined results suggest that the enhanced mutation
      frequency may be due to increased pausing at netropsin-modified polyadenosine
      tracts. Therefore, netropsin and related A-T binding chemicals may selectively
      enhance frameshift mutagenesis induced by HIV RT and yield predominantly non
      viable virus.

PMID- 7510389
TI  - Can hammerhead ribozymes be efficient tools to inactivate gene function?
AB  - In order to improve hammerhead ribozyme efficiency and specificity, we have
      analyzed, both in vitro and in vivo, the activity of a series of
      ribozyme/substrate combinations that have the same target sequence but differ in
      the length of the ribozyme/substrate duplex or in their structure, i.e., the
      total length of the RNA. In vitro, we have found that optimal kcat/Km (at 37
      degrees C) is obtained when the ribozyme/substrate duplex has a length of 12
      bases, which according to the base composition represents a calculated free
      energy of binding of -16 kcal/mol. We discuss the importance of this value for
      ribozyme specificity and present strategies that may improve it. Increasing the
      length of the duplex from 14 to 17 bases (from -19 to -26 kcal/mol) produces a
      reduced ribozyme activity which is probably due to a slower rate of product
      dissociation. In addition, inclusion of either the substrate or the ribozyme in a
      long transcript produces a reduction (10 fold) of the kcat/Km, probably because
      of a different accessibility of the target sequence. In vivo, the activity of the
      trans-acting ribozyme was extremely low and detected in only one case: with a
      ribozyme/substrate duplex length of 13 bases and with both ribozyme and substrate
      embedded in short RNAs expressed at a very high level. The similarity of the
      results obtained in vitro and in vivo indicates that it is possible to use an in
      vitro system to optimize ribozymes which are to be used in vivo. Satisfactory
      results were obtained in vivo only with cisacting ribozymes. Altogether these
      results suggest that the ribozyme/substrate hybridization step is the limiting
      step in vivo and therefore it is not clear if ribozymes represent an improvement
      over antisense RNAs.

PMID- 7510390
TI  - Higher-order structure of bovine mitochondrial tRNA(Phe) lacking the 'conserved'
      GG and T psi CG sequences as inferred by enzymatic and chemical probing.
AB  - Bovine mitochondrial (mt) phenylalanine tRNA (tRNA(Phe)), which lacks the
      'conserved' GG and T psi YCG sequences, was efficiently purified by the selective
      hybridization method using a solid phase DNA probe. The entire nucleotide
      sequence of the tRNA, including modified nucleotides, was determined and its
      higher-order structure was investigated using RNaseT2 and chemical reagents as
      structural probes. The D and T loop regions as well as the anticodon loop region
      were accessible to RNaseT2, and the N-3 positions of cytidines present in the D
      and T loops were easily modified under the native conditions in the presence of
      10mM Mg2+. On the other hand, the nucleotides present in the extra loop were
      protected from the chemical modification under the native conditions. From the
      results of these probing analyses and a comparison of the sequences of
      mitochondrial tRNA(Phe) genes from various organisms, it was inferred that bovine
      mt tRNA(Phe) lacks the D loop/T loop tertiary interactions, but does have the
      canonical extra loop/D stem interactions, which seem to be the main factor for
      bovine mt tRNA(Phe) to preserve its L-shaped higher-order structure.

PMID- 7510391
TI  - Micrococcal nuclease digestion of nuclei reveals extended nucleosome ladders
      having anomalous DNA lengths for chromatin assembled on non-replicating plasmids
      in transfected cells.
AB  - The chromatin structures of a variety of plasmids and plasmid constructions,
      transiently transfected into mouse Ltk- cells using the DEAE-dextran procedure,
      were studied by micrococcal nuclease digestion of nuclei and Southern
      hybridization. Although regularly arranged nucleosome-like particles clearly were
      formed on the transfected DNA, the nucleosome ladders, in some cases with 13-14
      bands, were anomalous. Most often, a ladder of DNA fragments with lengths of
      approximately 300, 500, 700, 900 bp, etc. was generated. In contrast, typical 180
      190 bp multiples were generated from bulk cellular or endogenous beta-actin gene
      chromatin. Very similar results were obtained with all DNA's transfected, and in
      a variety of cell lines, provided that plasmid replication did not occur.
      Additionally, after digestion of nuclei, about 90% of the chromatin fragments
      that contained transfected DNA sequences could not be solubilized at low ionic
      strength, in contrast with bulk cellular chromatin, suggesting association with
      nuclear structures or nuclear matrix. The remaining 10% of transfected DNA
      sequences, arising from soluble chromatin fragments, generated a typical
      nucleosome ladder. These results are consistent with the idea that assembly of
      atypical chromatin structures might be induced by proximity to elements of the
      nuclear pore complex or by nuclear compartmentalization.

PMID- 7510392
TI  - Polynucleotide phosphorylase of Escherichia coli induces the degradation of its
      RNase III processed messenger by preventing its translation.
AB  - Polynucleotide phosphorylase, a 3' to 5' processive exoribonuclease is post
      transcriptionally autocontrolled and it was previously shown that this control is
      dependent on a 5' processing by RNase III. In this paper, the mechanism of
      regulation is analyzed by studying the properties of a pnp-lacZ translational
      gene fusion. It is shown that this message is stable, even when processed by
      RNase III, and that the degradation rate is directly linked to the intracellular
      concentration of polynucleotide phosphorylase or to the pnp-lacZ messenger
      translation rate. Mutations able to decrease the level of repression are all
      located in the ribosome loading site. Taken together, these results suggest that
      polynucleotide phosphorylase is able to recognize specifically the processed
      messenger and to prevent its translation, thus allowing degradation of the
      message.

PMID- 7510393
TI  - Ultraviolet light-induced cleavage of DNA in the presence of iodoHoechst 33258:
      the sequence specificity of the reaction.
AB  - IodoHoechst 33258 sensitizes DNA to cleavage by near ultraviolet light (UV-A).
      Following an earlier study which showed that the UV-induced cleavage is at
      discrete locations corresponding to the ligand binding sites, this paper reports
      a more extensive analysis of the sequence specificity of cleavage. The
      experiments involved use of double-stranded DNA synthesised on primed M13
      templates. Analysis of cleavage in a 280bp sequence in M13mp18 and a 310bp
      sequence in three M13mp9 clones ('alpha-32', 'alpha-82' and 'alpha-22') derived
      from human alpha-DNA, showed that for all of the twenty-nine strong and very
      strong damage sites, cleavage was at the 3' end of a run of three or more
      consecutive AT base pairs. The extent of cleavage was higher for sites with
      consecutive Ts than for consecutive As, and greatest for the sequence cTTTTca.
      Comparison of three closely-related alpha-DNA clones enabled assessment of single
      bp changes and essentially confirmed the results of detailed analysis of binding
      cleavage sites in mp18 and alpha-32. Decreasing the input ratio of
      iodoHoechst/per bp DNA from 0.13 to 0.013 altered the sequence specificity, and
      sites possessing only three consecutive AT bps were generally not cleaved. The
      contributions of both the strength of ligand binding and the efficiency of
      photolytic cleavage to the overall extent of cleavage by UV/iodoHoechst are
      discussed, in view of the potential utility of the ligand as a probe of DNA
      conformation.

PMID- 7510394
TI  - Cloning of the multifunctional rat apurinic/apyrimidinic endonuclease
      (rAPEN)/redox factor from an immature T cell line.

PMID- 7510395
TI  - R17 coat protein binding site: a convenient reporter for in vitro transcription.

PMID- 7510398
TI  - Conformational heterogeneity in the Salmonella typhimurium pyrC and pyrD leader
      mRNAs produced in vivo.
AB  - In Salmonella typhimurium, different conformations of the pyrC and pyrD leader
      transcripts are produced as a result of nucleotide sensitive selection of the
      transcriptional start site. The CTP-initiated transcripts, synthesized at high
      intracellular CTP/GTP pool ratios (repressing conditions), have the potential of
      forming a stable secondary structure at the 5' end, thereby sequestering the site
      for translational initiation. At low CTP/GTP pool ratios (derepressing
      conditions), transcription starts 2-3 bp further downstream, resulting in
      transcripts with limited potential for stem-loop formation and therefore open for
      translational initiation. The conformation of the leader regions of wild type
      pyrC and pyrD mRNA has been investigated by chemical and enzymatic probing of RNA
      isolated from cultures grown in repressing and derepressing conditions. As
      controls and to obtain further information on the relation between the leader RNA
      conformation and the regulatory mechanism, the probing experiments also included
      pyrC and pyrD mRNA from mutants that contain a base substitution at a position
      that destabilizes the putative hairpin. In accordance with predictions based on
      the nucleotide sequence, the results showed that the 5' end of pyrC and pyrD
      leader mRNA isolated from repressed cultures is folded into a secondary
      structure, whereas it is largely unstructured in mRNA isolated from derepressed
      cultures.

PMID- 7510399
TI  - Palliative care. Terminal dehydration.

PMID- 7510396
TI  - One of two Ets-binding sites in the cytokeratin EndoA enhancer is essential for
      enhancer activity and binds to Ets-2 related proteins.
AB  - Expression of the mouse cytokeratin EndoA gene is restricted in endodermal and
      epithelial cells, and is regulated by an enhancer that is located 1 kilobase (kb)
      3' downstream from the gene. The enhancer consists of six direct repeats, of
      which each contains two predicted Ets binding sites (EBS1 and EBS2) containing
      GGAA as a core. Mutation analysis showed that EBS1 is essential for the enhancer
      activity and additional effects of EBS2, suggesting that some Ets-related
      proteins bind and activate the enhancer through EBS1. We also showed that Ets-2
      mRNA is expressed in PYS-2 cells and that Ets-2 protein produced by E. coli
      interacts with EBS1 but not with EBS2. Using co-transfection assays, we showed
      that Ets-2 can trans-activate the enhancer in PYS-2 cells. Mutations that impair
      Ets-2 binding abolished the activity of the EndoA enhancer. The results obtained
      from the binding competition assay using an Ets-2 specific antibody, however,
      suggest that EBS1 binds to an Ets protein which is distinct from Ets-2. These
      data show that Ets-2 related protein binds and activates the EndoA enhancer in a
      sequence-specific fashion.

PMID- 7510400
TI  - Palliative care. All-consuming problem.

PMID- 7510401
TI  - [Fibromyalgia: from information to questions].

PMID- 7510397
TI  - Positions 13 and 914 in Escherichia coli 16S ribosomal RNA are involved in the
      control of translational accuracy.
AB  - Using a conditional expression system with the temperature-inducible lambda PL
      promoter, we previously showed that the single mutations 13U-->A and 914A-->U,
      and the double mutation 13U-->A and 914A-->U in Escherichia coli 16S ribosomal
      RNA impair the binding of streptomycin (Pinard et al., The FASEB Journal, 1993,
      7, 173-176). In this study, we found that the two single mutations and the double
      mutation increase translational fidelity, reducing in vivo readthrough of
      nonsense codons and frameshifting, and decreasing in vitro misincorporation in a
      poly(U)-directed system. Using oligodeoxyribonucleotide probes which hybridize to
      the 530 loop and to the 1400 region of 16S rRNA, two regions involved in the
      control of tRNA binding to the A site, we observed that the mutations in rRNA
      increase the binding of the probe to the 530 loop but not to the 1400 region. We
      suggest that the mutations at positions 13 and 914 of 16S rRNA induce a
      conformational rearrangement in the 530 loop, which contributes to the increased
      accuracy of the ribosome.

PMID- 7510402
TI  - An idiotope--anti-idiotope complex and the structural basis of molecular
      mimicking.

PMID- 7510403
TI  - Remarkable archaeal diversity detected in a Yellowstone National Park hot spring
      environment.
AB  - Of the three primary phylogenetic domains--Archaea (archaebacteria), Bacteria
      (eubacteria), and Eucarya (eukaryotes)--Archaea is the least understood in terms
      of its diversity, physiologies, and ecological panorama. Although many species of
      Crenarchaeota (one of the two recognized archaeal kingdoms sensu Woese [Woese, C.
      R., Kandler, O. & Wheelis, M. L. (1990) Proc. Natl. Acad. Sci. USA 87, 4576
      4579]) have been isolated, they constitute a relatively tight-knit cluster of
      lineages in phylogenetic analyses of rRNA sequences. It seemed possible that this
      limited diversity is merely apparent and reflects only a failure to culture
      organisms, not their absence. We report here phylogenetic characterization of
      many archaeal small subunit rRNA gene sequences obtained by polymerase chain
      reaction amplification of mixed population DNA extracted directly from sediment
      of a hot spring in Yellowstone National Park. This approach obviates the need for
      cultivation to identify organisms. The analyses document the existence not only
      of species belonging to well-characterized crenarchaeal genera or families but
      also of crenarchaeal species for which no close relatives have so far been found.
      The large number of distinct archaeal sequence types retrieved from this single
      hot spring was unexpected and demonstrates that Crenarchaeota is a much more
      diverse group than was previously suspected. The results have impact on our
      concepts of the phylogenetic organization of Archaea.

PMID- 7510404
TI  - Fibroblast growth factor, but not activin, is a potent activator of mitogen
      activated protein kinase in Xenopus explants.
AB  - Isolated explants from the animal hemisphere of Xenopus embryos were incubated
      with Xenopus basic fibroblast growth factor (XbFGF) or human activin A. XbFGF
      incubation resulted in the rapid activation of mitogen-activated protein kinase
      (MAPK) and ribosomal S6 protein kinase (pp90rsk) in a dose-dependent manner with
      the highest levels of activation occurring at 50 ng/ml. Maximal activation
      occurred within 6-10 min after the addition of growth factor, and the activity of
      both kinases declined to unstimulated levels after 30 min. Activin was unable to
      activate either MAPK or pp90rsk in the Xenopus explants to a substantial level,
      although it induced dorsal mesoderm better than XbFGF under the same experimental
      conditions. The regulatory protein Xwnt-8 did not activate MAPK, nor did it
      enhance the activation of MAPK by XbFGF. XbFGF was able to activate MAPK through
      at least the midgastrula stage, suggesting that this family of growth factors may
      have a role in gastrula-stage events.

PMID- 7510405
TI  - Nitric oxide: a mediator in rat tubular hypoxia/reoxygenation injury.
AB  - Nitric oxide (NO), among several other functions, may play a role in hypoxia and
      reoxygenation injury due to its free radical nature and high reactivity with the
      superoxide radical to yield peroxynitrite, an oxidant molecule. The present study
      was undertaken to evaluate a potential role for NO, either endogenous or
      exogenous, in a model of hypoxia/reoxygenation (H/R) in freshly isolated rat
      proximal tubules. NO synthase activity, as assessed by conversion of L
      [3H]arginine to L-[3H]citrulline, was detected in normoxic tubules. This activity
      could be inhibited by N-nitro-L-arginine methyl ester (L-NAME), a NO synthase
      inhibitor, and was stimulated by 15 min of hypoxia. The injury in proximal
      tubules caused by 15 min of hypoxia followed by 35 min of reoxygenation was
      completely prevented by L-NAME as assessed by release of lactate dehydrogenase,
      whereas D-NAME, which does not inhibit NO synthase, had no effect. In contrast, L
      arginine (NO substrate) enhanced the H/R injury. These effects were paralleled by
      nitrite/nitrate production. In separate experiments, the addition of sodium
      nitroprusside, a NO donor, to proximal tubules enhanced the H/R injury; this
      effect could be blocked by hemoglobin, a NO scavenger. Also, addition of
      nitroprusside reversed L-NAME protection against H/R injury. These results
      demonstrate that NO is synthesized in rat proximal tubules and participates as
      one of the mediators in rat tubular H/R injury.

PMID- 7510406
TI  - Single-channel currents trigger action potentials in small cultured hippocampal
      neurons.
AB  - Spontaneous neuronal impulse activity appears to play a key role in some neural
      processes, such as the normal establishment of interneuronal connections during
      development. In addition, spontaneous impulses may be essential for the
      functional operation of neuronal networks. Mechanisms of spontaneous non
      pacemaker impulse generation are, however, not well known. In this work,
      spontaneous electrical activity in small cultured hippocampal neurons from rat
      was studied with tight-seal recording techniques. The results demonstrate that
      spontaneous individual openings of single ion channels can trigger impulse
      generation in these high-resistance cells. First, impulses recorded in the whole
      cell mode were apparently induced by spontaneous plateau-potential events showing
      the characteristics expected from individual openings and closures of ion
      channels. Second, patch-clamp recordings in the cell-attached configuration
      showed that openings of single ion channels in the patch membrane could trigger
      cellular impulses, detected as biphasic current deflections. These findings
      suggest that the random gating of ion channel molecules can be used as a
      mechanism for stochastic triggering of spontaneous impulses in mammalian central
      neurons.

PMID- 7510408
TI  - Enthalpy of hydrogen bond formation in a protein-ligand binding reaction.
AB  - Parallel measurements of the thermodynamics (free-energy, enthalpy, entropy and
      heat-capacity changes) of ligand binding to FK506 binding protein (FKBP-12) in
      H2O and D2O have been performed in an effort to probe the energetic contributions
      of single protein-ligand hydrogen bonds formed in the binding reactions. Changing
      tyrosine-82 to phenylalanine in FKBP-12 abolishes protein-ligand hydrogen bond
      interactions in the FKBP-12 complexes with tacrolimus or rapamycin and leads to a
      large apparent enthalpic stabilization of binding in both H2O and D2O. High
      resolution crystallographic analysis reveals that two water molecules bound to
      the tyrosine-82 hydroxyl group in unliganded FKBP-12 are displaced upon formation
      of the protein-ligand complexes. A thermodynamic analysis is presented that
      suggests that the removal of polar atoms from water contributes a highly
      unfavorable enthalpy change to the formation of C=O...HO hydrogen bonds as they
      occur in the processes of protein folding and ligand binding. Despite the less
      favorable enthalpy change, the entropic advantage of displacing two water
      molecules upon binding leads to a slightly more favorable free-energy change of
      binding in the reactions with wild-type FKBP-12.

PMID- 7510409
TI  - Developing a poster presentation.
AB  - A poster presentation gives a summary of information in a visual format. Poster
      topics can focus on research, teaching, or projects. Careful layout and
      meticulous proofreading and editing of the information are important to a
      poster's success. The practical strategies mentioned in this article can help
      nurses develop and enhance their poster presentation skills.

PMID- 7510407
TI  - K+ currents expressed from the guinea pig cardiac IsK protein are enhanced by
      activators of protein kinase C.
AB  - We have isolated cardiac cDNA and genomic clones encoding the guinea pig IsK
      protein. The deduced amino acid sequence is approximately 78% identical to the
      rat, mouse, and human variants of this channel, and the structure of the gene
      encoding the protein is also similar to that in other species. For example, the
      gene is present only once in the haploid genome, the protein-coding sequence is
      present on a single uninterrupted exon, an intron exists in the 5' untranslated
      domain, and multiple alternative polyadenylation sites are used in processing the
      transcript. Expression of the guinea pig protein in Xenopus oocytes results in a
      slowly activating, voltage-dependent K+ current, IsK, similar to those expressed
      previously from the rat, mouse, and human genes. However, in sharp contrast to
      the rat and mouse currents, activation of protein kinase C with phorbol esters
      increases the amplitude of the guinea pig IsK current, analogous to its effects
      on the endogenous IKs current in guinea pig cardiac myocytes. Mutagenesis of the
      guinea pig cDNA to alter four cytoplasmic amino acid residues alters the
      phenotype of the current response to protein kinase C from enhancement to
      inhibition, mimicking that of rat and mouse IsK currents. This mutation is
      consistent with reports that phosphorylation of Ser-102 by protein kinase C
      decreases the current amplitude. These data explain previously reported
      differences in the regulatory properties between recombinant rat or mouse IsK
      channels and native guinea pig IKs channels and provide further evidence that the
      IsK protein forms the channels that underlie the IKs current in the heart.

PMID- 7510410
TI  - Serum pancreas-specific protein in acute pancreatitis. Its clinical utility in
      comparison with serum amylase.
AB  - To compare the clinical utility of serum pancreas-specific protein and serum
      amylase in the diagnosis of acute pancreatitis, the study was conducted in 134
      normal subjects and 70 patients (36 with acute pancreatitis and 34 with other
      acute abdominal diseases as control group). The serum level of pancreas-specific
      protein in 134 healthy adults was 29.6 +/- 1.6 micrograms/l, with 95% within 7.3
      67.2 micrograms/l. The upper reference limit was set at 70 micrograms/l. Serum
      levels of pancreas-specific protein and amylase within 12 h of arrival were
      significantly higher in patients with acute pancreatitis than in the control
      group (647.3 +/- 79.3 versus 33.8 +/- 4.8 micrograms/l (p < 0.0001) and 2536 +/-
      344 versus 175 +/- 35 IU/l (p < 0.0001)). No significant difference in the levels
      of pancreas-specific protein was noted between biliary and alcoholic pancreatitis
      or between severe and mild attacks. The sensitivity, specificity, and accuracy of
      diagnosing acute pancreatitis were 100%, 94.1%, and 97.1% with serum pancreas
      specific protein > 70 micrograms/l and 97.2%, 91.2%, and 94.3% with serum amylase
      > 360 IU/l. The result demonstrated that pancreas-specific protein may be a good
      serum marker in the diagnosis of acute pancreatitis.

PMID- 7510411
TI  - Alkali-treated LPS of Yersinia enterocolitica does not induce expression of E
      selectin, ICAM-1 or VCAM-1 on endothelial cells but may mediate antibody- and
      complement-dependent cell injury.
AB  - Lipopolysaccharide (LPS) prepared from a rough mutant of Salmonella typhimurium
      and deacylated enzymatically (dLPS) does not promote neutrophil adherence to
      human umbilical vein endothelial cells (HUVECs). This paper reports that
      similarly, a smooth form of LPS prepared from Yersinia enterocolitica O:3, a
      serotype known to trigger reactive arthritis in humans, and treated with alkali
      (yersinia LPS-OH) failed to augment neutrophil adherence to HUVECs. Studies of
      the mechanism underlying the poor augmentation revealed that neither
      enzymatically deacylated LPS from Escherichia coli J5 (J5 dLPS) nor yersinia LPS
      OH stimulated expression of endothelial cell adhesion molecules E-selectin, VCAM
      1 and ICAM-1, whereas both intact J5 LPS and yersinia LPS were stimulatory.
      Impaired up-regulation could not be explained by decreased binding of yersinia
      LPS-OH to HUVECs. Furthermore, 51Cr-labelled HUVECs treated with different
      concentrations of yersinia LPS-OH released 51Cr in the presence of anti-yersinia
      anti-O antibody and complement. J5 dLPS and yersinia LPS-OH inhibited up
      regulation of the adhesion molecules induced by J5 LPS and yersinia LPS but not
      that induced by tumour necrosis factor alpha. Taken together, the results suggest
      that although yersinia LPS-OH can depress development of acute inflammation by
      inhibiting up-regulation of endothelial-cell adhesion molecules, sufficient LPS
      OH is bound to induce cell injury and thereby inflammation in the presence of
      specific antibody and complement. The findings may have pathogenetic implications
      in yersinia-triggered reactive arthritis characterized by dissemination of
      yersinia LPS throughout the body.

PMID- 7510412
TI  - Enhanced ICAM-1-dependent adhesion of myelomonocytic cells expressing increased
      levels of beta 2-integrins and CD43.
AB  - Interaction of ICAM-1 and its ligands plays an important role in the leukocyte
      binding to endothelium. The best characterized ICAM-ligands belong to the family
      of beta 2-integrins (CD11/CD18), but recently it has been suggested that CD43, a
      molecule with no structural resemblance to integrins binds ICAM-1 also. On the
      leukocytes the main regulatory pathway for ICAM-mediated binding is believed to
      be a short-term regulation of the avidity of CD11/CD18. In this study the authors
      investigated whether a quantitative increase in the surface expression of ICAM
      ligands also can lead to enhanced binding to purified ICAM-1. PMA-treatment
      differentiates myelomonocytic cell lines into macrophages with a concomitant
      increase in the surface expression and mRNA-levels of the beta 2-integrin alpha-
      and beta-chains as well as that of CD43, another ICAM-ligand. The binding of the
      PMA-treated THP-1 cells to ICAM-1 was increased simultaneously compared to non
      treated cells. The binding was blocked completely with antibodies to CD18 and
      ICAM-1. It is concluded that in addition to the transient qualitative regulation,
      a long-term quantitative regulation of ICAM-1 ligands also plays a role in
      increasing the adhesiveness of myelomonocytic cells. This may be relevant in
      chronic inflammation episodes.

PMID- 7510413
TI  - Expression of CZ-1: a CD45RB epitope on progenitors of natural killer and other
      haematopoietic cells.
AB  - CZ-1 is a novel sialic acid-dependent epitope of the murine CD45RB molecule which
      is expressed on cells that proliferate when cultured in IL-2. Because IL-2
      appears to be important in the differentiation of NK cells, the authors examined
      the expression of CZ-1 on immature NK-lineage cells within the bone marrow. All
      mature NK1.1+ cells as well as their NK1.1- IL-2 responsive precursors were CZ
      1+. Furthermore, IL-2 unresponsive transplantable NK progenitor cells expressed
      CZ-1 also. To examine expression of CZ-1 on other immature lymphoid progenitor
      cells, CZ-1+ and CZ-1- marrow cells were transplanted into lightly irradiated
      scid mice. Transfer of CZ-1+ cells resulted in rapid and sustained generation of
      thymocytes and splenic B cells, whereas CZ-1- cells caused delayed repopulation.
      This suggested that the slowly repopulating pluripotent stem cells lacked CZ-1.
      Therefore, expression of CZ-1 on Ly6+ Lin- c-kit+ cells, highly enriched for
      pluripotent stem cells, was examined. This population appeared to be
      homogeneously CZ-1dull. Thus, it appears that expression of CZ-1 is
      developmentally regulated, with differentiation associated with increased
      expression. Since CZ-1 is expressed on a protein tyrosine phosphatase, it is
      likely that this molecule regulates differentiation of NK and other lymphoid
      cells.

PMID- 7510415
TI  - Characterization of a 58- and a 78-kD monocytic membrane protein with affinity to
      the acetylcholine receptor in myasthenia gravis patients.
AB  - The autoimmune disease myasthenia gravis (MG), caused by the effect of specific
      antibodies, directed towards the nicotinic acetylcholine receptor, is triggered
      by autoantigen-specific T cells. In order to investigate cellular parts of the
      immune response in MG, the authors investigated the binding of the nicotinic
      acetylcholine receptor (AChR) to peripheral blood mononuclear cells (PBMC) from
      MG patients. AChR binding cells were identified by rosetting experiments using
      AChR-coated fluorescein beads. Applying this technique, a significant percentage
      of PBMC (21.2 +/- 7.65%) from MG patients formed rosettes with AChR-coated beads.
      Membrane preparations of nycodenz- or percoll-separated monocytes from MG
      patients or T-cell depleted monocytic subpopulations were applied to SDS-PAGE
      under reducing conditions. Ligand-blotting studies with biotinylated AChRs
      revealed two cell-membrane proteins with molecular weights of 58- and 78-kD. In
      parallel the same results were obtained by affinity chromatography of monocytic
      membrane proteins using AChR-sepharose. A possible interference of anti-AChR IgG
      was excluded. The 58- and the 78-kD proteins are detectable under reducing
      conditions by ligand blotting with AChR-biotin, while under non-reducing
      conditions only the 58-kD protein can be detected. Furthermore, in experiments
      using Endoglycosidase-H, the 58-kD protein appears to be non-glycosylated, while
      the 78-kD protein bears carbohydrates. These findings suggest that monocytes
      which bind the AChR via specific membrane proteins on their surface might act as
      antigen-presenting cells and may lead to an induction of the T-cell response, in
      the early phase of the disease.

PMID- 7510416
TI  - Human complement activation by polygeline and dextran 70.
AB  - The complement cascade is activated during cardiopulmonary bypass (CPB) and in
      trauma victims. In order to study whether plasma expanders may contribute to
      complement activation in these settings, fresh human serum was incubated with
      dextran 70 and polygeline. C3-activation products and the terminal complement
      complex (TCC) were quantified in enzyme immunoassays. At 37 degrees C, dextran
      caused immediate, dose-dependent C3 activation and TCC formation with decline
      later in the rate of TCC formation relative to serum-saline controls. High doses
      of polygeline caused slight activation after 15-30 min. The authors tested also
      the activation under conditions comparable to those found during clinical CPB.
      Activation induced by dextran and polygeline was increased by dilution of the
      serum. Furthermore, the plasma expanders counteracted the well-known inhibitory
      effects of heparin (4 IU/ml) and moderate hypothermia (30 degrees C) on
      complement activation. The authors conclude that dextran, and to a lesser extent
      polygeline, may contribute to complement activation during CPB and other clinical
      settings such as shock treatment.

PMID- 7510417
TI  - High-resolution molecular discrimination by RNA.
AB  - Species of RNA that bind with high affinity and specificity to the bronchodilator
      theophylline were identified by selection from an oligonucleotide library. One
      RNA molecule binds to theophylline with a dissociation constant Kd of 0.1 microM.
      This binding affinity is 10,000-fold greater than the RNA molecule's affinity for
      caffeine, which differs from theophylline only by a methyl group at nitrogen atom
      N-7. Analysis by nuclear magnetic resonance indicates that this RNA molecule
      undergoes a significant change in its conformation or dynamics upon theophylline
      binding. Binding studies of compounds chemically related to theophylline have
      revealed structural features required for the observed binding specificity. These
      results demonstrate the ability of RNA molecules to exhibit an extremely high
      degree of ligand recognition and discrimination.

PMID- 7510414
TI  - Formation of the terminal complement complex on agarose beads: further evidence
      that vitronectin (complement S-protein) inhibits C9 polymerization.
AB  - Vitronectin occupies the metastable binding site of C5b-7, which is unable to
      insert membranes as part of the complement lytic attack. Some evidence has been
      presented that vitronectin inhibits also membrane-associated pore formation by
      inhibiting C9 polymerization in the terminal complement complex (TCC). The
      authors wished to add to this background by studying the effect of vitronectin on
      formation of TCC on a carbohydrate surface like agarose beads, an alternative
      complement pathway activator. Bound TCC was detected by monoclonal and polyclonal
      antibodies to C9-neoepitopes. Soluble SC5b-7 and TCC (SC5b-9) did not bind to the
      agarose beads. Using serum or isolated complement factors for the alternative and
      terminal pathways, the authors found that vitronectin reduced the density of C9
      neoepitopes on the beads. As there was no convincing evidence for association of
      vitronectin with the factors C5b-8 of the agarose-bound TCC, it was concluded
      that vitronectin bound directly to C9 in TCC and inhibited C9 polymerization
      within the complex. The authors have shown that TCC can bind to a carbohydrate
      surface like agarose (an alternating polymer of galactose moieties) in the
      absence of lipid. These results suggest that vitronectin can limit the lytic
      effect of membrane-bound TCC by inhibiting C9 polymerization.

PMID- 7510418
TI  - Reacting to gasoline additives.

PMID- 7510420
TI  - Radiation-induced changes in long-term survivors of childhood cancer after
      treatment with radiation therapy.
AB  - This article has provided an account of the delayed effects after successful
      treatment for childhood cancer. Particular emphasis has been placed on sequelae
      induced by radiation therapy. Chemotherapy-related complications that may
      simulate or aggravate these sequelae also are recorded. The alterations induced
      by radiation therapy and chemotherapy are not limited to the organs and tissues
      described in this article. Subtle, and at times psychologically devastating,
      sequelae also may be encountered (eg, sterility due to radiation and
      chemotherapeutic effects on the gonads). However, an attempt has been made only
      to identify those complications that may be more readily detected by means of
      radiographic studies. It is recommended that ongoing surveillance of the long
      term successfully treated childhood cancer survivor be conducted in order to
      detect such complications. Early detection will assist in implementing
      appropriate treatment, minimizing delayed effects, and maximizing the quality of
      life. Periodic radiographic studies of previously radiated areas at regular
      intervals therefore appears appropriate.

PMID- 7510421
TI  - [From pedagogy to therapy: learning groups in the day hospital].

PMID- 7510419
TI  - Requirement for transcription factor IRF-1 in NO synthase induction in
      macrophages.
AB  - Production of nitric oxide (NO) by macrophages is important for the killing of
      intracellular infectious agents. Interferon (IFN)-gamma and lipopolysaccharide
      stimulate NO production by transcriptionally up-regulating the inducible NO
      synthase (iNOS). Macrophages from mice with a targeted disruption of the IFN
      regulatory factor-1 (IRF-1) gene (IRF-1-/- mice) produced little or no NO and
      synthesized barely detectable iNOS messenger RNA in response to stimulation. Two
      adjacent IRF-1 response elements were identified in the iNOS promoter. Infection
      with Mycobacterium bovis (BCG) was more severe in IRF-1-/- mice than in wild-type
      mice. Thus, IRF-1 is essential for iNOS activation in murine macrophages.

PMID- 7510423
TI  - Granulocyte-macrophage colony-stimulating factor and granulocyte colony
      stimulating factor: differential action on incisional wound healing.
AB  - BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF)
      specifically stimulates granulocyte, macrophage, and eosinophil colonies;
      granulocyte colony-stimulating factor (G-CSF) acts directly on neutrophil
      restricted progenitor cells in their proliferation. Those cells have been
      implicated in the process of wound healing. METHODS: Paired 6 cm incisions were
      made on rats; GM-CSF or G-CSF was given systemically (100 micrograms/kg/dose) or
      locally (30 micrograms/wound). The controls received vehicle alone. Impaired
      healing was induced by injection of methylprednisolone (30 mg/kg). White blood
      cells (WBC) were counted at day 2 after treatment. Tissue strips were evaluated
      for tensiometry and histologic features at days 7 and 14 after wounding. RESULTS:
      For local GM-CSF treated incisions, the breaking strength was 25% stronger than
      controls at day 7 (p = 0.004), 36% at day 14 (p < 0.0001), and 42% at day 7 (p =
      0.012) in impaired animals. Local G-CSF and systemic GM-CSF and G-CSF increased
      circulating WBC (p < 0.05), but they had no effects on healing. Histologic
      studies revealed an increase of wound cellulity at day 7 and day 14 in topical GM
      CSF treated wounds. CONCLUSIONS: These results suggest GM-CSF is an activator of
      tissue macrophages and that increasing circulating WBC did not affect wound
      healing.

PMID- 7510424
TI  - Effect of detergent on alveolar particle clearance due to large tidal
      ventilation.
AB  - BACKGROUND: It has recently been shown that large tidal volume ventilation
      accelerates the alveolar clearance of insoluble particles and this may be related
      to accelerated surfactant evacuation from the alveolus into the airway. The aim
      of this study was to investigate if the effect of large tidal volume ventilation
      is modified in an experimental model of surfactant dysfunction. METHODS:
      Fluorescent latex particles of 0.63 microns diameter were administered in aerosol
      form to 30 rabbits during anaesthesia with thiopentone and mechanical
      ventilation. Six animals were killed immediately after aerosol administration in
      order to show the initial deposition of particles. Twenty four animals were
      divided into two groups and ventilated for three hours with either large tidal
      volume (mean tidal volume 30 ml/kg) or conventional ventilation (mean tidal
      volume 12.5 ml/kg). Six rabbits in each of the two groups were administered
      either the synthetic detergent dioctyl sodium sulphosuccinate in aerosol form or
      aerosolised vehicle. After the period of experimental ventilation the lungs were
      removed and dried in the expanded state. Particles in the alveolar region were
      counted with fluorescent microscopy in sections of the lung. RESULTS: Compared
      with the baseline group (mean (SD) 24.8 (9.9)) the count of residual alveolar
      particles was lower after large tidal volume ventilation in the absence of
      detergent aerosol (13.2 (6.5)). Particle count after large tidal volume
      ventilation and detergent treatment (23.3 (6.4)) was similar to that in the
      baseline group and to that in the groups exposed to conventional ventilation.
      CONCLUSIONS: The increase in alveolar clearance of insoluble particles caused by
      large tidal volume ventilation is inhibited by detergent aerosol. This might be
      due to reduced stability of the surfactant film after detergent aerosol.

PMID- 7510422
TI  - Methylation analysis by genomic sequencing of 5' region of mouse Pgk-1 gene and a
      cautionary note concerning the method.
AB  - We have used genomic sequencing aided by ligation-mediated PCR (LMPCR) to assay
      for 5-methylcytosine in the CpG-rich promoter region of the mouse X-linked
      phosphoglycerate kinase gene (Pgk-1). Earlier studies showed that there was very
      heavy methylation of CpG dinucleotides in the CpG-rich promoter of the human PGK1
      gene on the inactive X chromosome (the Xi), but that these same sites were
      completely unmethylated on the active X chromosome (the Xa). For mouse Pgk-1,
      previous restriction enzyme analysis had shown apparently complete methylation of
      only one cytosine in the promoter region on the Xi, at HpaII site H7, which is
      located in the untranslated region, 28 nucleotides upstream of the translation
      start site. We analyzed this potentially critical region by combining the use of
      HpaII with LMPCR, and find that the CpG dinucleotides near H7 are either
      unmethylated or only partially methylated on the Xi. LMPCR analysis of male and
      female DNA over a 490-bp sequence including the promoter and enhancer extend the
      finding of relative hypomethylation on the mouse Xi to include all CpG
      dinucleotides in this region. These results are relevant to the role of DNA
      methylation in stabilizing the inactive state of chromatin. In addition, we find
      that caution must be exercised in using LMPCR for methylation analysis of some
      sequences. A DNA concentration-dependent band-suppression artifact can
      incorrectly suggest methylation of both CpG and nonCpG dinucleotides.

PMID- 7510425
TI  - Endotoxin-induced tissue factor in human monocytes is dependent upon protein
      kinase C activation.
AB  - Tissue factor (TF) is a transmembrane receptor which, in association with factors
      VII and VIIa, activates factor IX and X, thereby activating the coagulation
      protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes
      transcribe, synthesize and express TF on their surface. We investigated whether
      LPS-induced TF in human monocytes is mediated by protein kinase C (PKC)
      activation. The PKC agonists phorbol 12-myristate 13-acetate (PMA) and phorbol
      12, 13 dibutyrate (PdBu) were both potent inducers of TF in human monocytes,
      whereas 4 alpha-12, 13 didecanoate (4 alpha-Pdd) had no such effect. Both LPS-
      and PMA-induced TF activity were inhibited, in a concentration dependent manner,
      by three different PKC inhibitors: H7, staurosporine and calphostin C. TF antigen
      determination confirmed that LPS-induced cell-surface TF protein levels decreased
      in parallel to TF functional activity under staurosporine treatment. Moreover,
      Northern blot analysis of total RNA from LPS- or PMA-stimulated monocytes showed
      a concentration-dependent decrease in TF mRNA levels in response to H7 and
      staurosporine. The decay rate of LPS-induced TF mRNA evaluated after the arrest
      of transcription by actinomycin D was not affected by the addition of
      staurosporine, suggesting that its inhibitory effect occurred at a
      transcriptional level. We conclude that LPS-induced production of TF and its mRNA
      by human monocytes are dependent on PKC activation.

PMID- 7510426
TI  - Inhibitory effect of staphylokinase on platelet aggregation.
AB  - We investigated the effect of staphylokinase (SAK), which has specific
      thrombolytic properties, on human platelet aggregation. Platelet aggregation
      induced with collagen was observed following preincubation of platelets in
      platelet-rich plasma (PRP) or washed platelet suspension (WP) with SAK at 37
      degrees C for 30 min. SAK inhibited platelet aggregation in PRP only at the
      highest examined concentration (1 x 10(-4) g/ml). Although SAK did not inhibit
      platelet aggregation in WP which contained fibrinogen, it did when the platelets
      had been preincubated with SAK and plasminogen. The most effective concentration
      in WP was 1 x 10(-6) g/ml. The effect could be inhibited by adding aprotinin or
      alpha 2-antiplasmin. The highest generation of plasmin in the same preincubation
      fluid was detected at 1 x 10(-6) g/ml SAK. We concluded that SAK can inhibit
      platelet aggregation in WP by generating plasmin and/or fibrinogen degradation
      products, but is only partially effective in PRP because of the existence of
      alpha 2-antiplasmin.

PMID- 7510427
TI  - A natural rubber drainage tube with antithrombogenic lumen surface.
AB  - A drainage tube was made by radiation vulcanization of a high polymeric substance
      based on natural rubber elastomers. Pentosan polysulphate sodium bound to a
      carrier substance (synthetic type 4A or 13X zeolite) was incorporated in the
      drainage tube which was then tested for its anticoagulant properties during
      perfusion with Tris buffer solution, citrated plasma, and blood, resp. The amount
      of pentosan polysulphate sodium released from the tube walls during perfusion
      with human citrated plasma in an open circulatory system was sufficient to exert
      an anticoagulant effect on the streaming plasma. This effect was corroborated by
      prolonged thrombin times and by unclottability in case of recalcified plasma
      samples in thrombelastographic studies. The antithrombogenicity test according to
      Chandler in a closed circulatory system revealed thrombus formation times (TFT)
      of more than 24 h (control: TFT = 1-3 min in native blood).

PMID- 7510428
TI  - Subcellular localization of metallothionein IIA in human bladder tumor cells
      using a novel epitope-specific antiserum.
AB  - Human metallothioneins (hMTs) are a family of highly homologous proteins thought
      to be critical in cellular protection against toxins. The comparative function of
      individual isoforms is, however, obscure. Antibodies to individual MT isoforms
      might help clarify this issue but their generation has been challenging. We now
      describe a strategy that has successfully produced an epitope-specific antiserum
      to a major human isoform, hMT IIA. The immunogen, a conjugated tridecyl amino
      acid synthetic peptide unique to residues 8-20 in hMT IIA (AAGDSCTCAGSCK),
      yielded an antiserum (B2) that reacted specifically with hMT IIA in a
      concentration- and titer-dependent manner and showed no reactivity with human or
      rabbit liver MT I or horse MTs. This antiserum recognized rabbit liver MT II and,
      surprisingly, also reacted weakly with chicken MT. MT amino acid sequence
      comparisons and peptide blocking studies suggested aspartate-11 and threonine-14
      are important antigenic determinants for B2. Using confocal immunofluorescence
      microscopy and B2 antiserum, we observed nuclear localization of hMT IIA with
      human bladder T24 tumor cells in exponential growth but more cytoplasmic
      localization at confluence. These results suggest the subcellular location of hMT
      IIA is a function of cell density in T24 bladder carcinoma cells. The general
      approach of epitope-specific antibodies may be useful for the generation of
      antibodies to other MT isoforms and for studying the role of individual MT
      isoforms in biology and toxicology.

PMID- 7510429
TI  - Subchronic dietary exposure to Aroclor 1254 in rats: accumulation of PCBs in
      liver, blood, and adipose tissue and its relationship to induction of various
      hepatic drug-metabolizing enzymes.
AB  - Female F344/NCr rats were exposed continuously (7-84 days) or discontinuously (7
      days exposure/21 days control diet or 28 days exposure/56 days control diet) to
      various dietary concentrations (1-100 ppm) of Aroclor 1254. There were dose- and
      time-dependent increases in PCB levels in liver, blood, and adipose tissue.
      Following removal of the rats from diet containing Aroclor 1254, there was a
      relatively rapid decrease in PCB levels, particularly in rats exposed to higher
      concentrations of Aroclor 1254. In parallel with the alterations in PCB levels
      observed, the rats showed striking dose- and time-dependent increases in hepatic
      levels of CYP1A1 and CYP1A2, as determined by various methods [RNA analysis,
      immunochemical detection, or measurement of the O-dealkylation of
      methoxyresorufin (CYP1A2) or ethoxyresorufin (CYP1A1)]. In rats removed from the
      Aroclor 1254 diet, catalytic activity for CYP1A1 as well as RNA levels for both
      CYP1A1 and CYP1A2 rapidly diminished. In contrast to the high levels of induction
      of CYP1A1 and CYP1A2 observed, limited induction (< 5-fold) of epoxide hydrolase,
      quinone oxidoreductase, and aldehyde dehydrogenase was detected, even in rats
      exposed to the highest concentration of Aroclor (100 ppm) for up to 84 days.
      Furthermore, induction of these non-CYP hepatic drug-metabolizing genes exhibited
      distinctly different concentration-response curves. The ratios of hepatic CYP1A1
      activity to hepatic PCB burden were similar for rats exposed continuously to
      Aroclor in the diet for 7, 28, or 84 days, and for rats exposed discontinuously
      (7 days Aroclor/21 days control diet or 28 days Aroclor/56 days control diet).
      Thus, hepatic PCB levels alone appeared to be reasonably predictive of CYP1A1
      levels under a variety of modes of exposure. When the ratio of CYP1A1 activity to
      adipose or blood PCB concentration was determined, similar ratios were observed
      for rats exposed continuously for 7, 28, or 84 days. However, lower ratios were
      observed for rats discontinuously exposed to Aroclor in the diet. These results
      have important implications with respect to: (a) employing PCB levels in various
      tissues to predict biological effects, and (b) determining different
      concentration-response curves for the various biological effects induced by PCBs.

PMID- 7510430
TI  - Nitric oxide and the cerebral circulation.
AB  - BACKGROUND: Nitric oxide (NO) is a potent vasodilator that was initially
      described as the mediator of endothelium-dependent relaxation (endothelium
      derived relaxing factor, EDRF). It is now known that NO is produced by a variety
      of other cell types. SUMMARY OF REVIEW: Endothelium produces NO (EDRF) under
      basal conditions and in response to a variety of vasoactive stimuli in large
      cerebral arteries and the cerebral microcirculation. Endothelium-dependent
      relaxation is impaired in the presence of several pathophysiological conditions.
      This impairment may contribute to cerebral ischemia or stroke. Activation of
      glutamate receptors appears to be a major stimulus for production of NO by
      neurons. Neuronally derived NO may mediate local increases in cerebral blood flow
      during increases in cerebral metabolism. NO synthase-containing neurons also
      innervate large cerebral arteries and cerebral arterioles on the brain surface.
      Activation of parasympathetic fibers that innervate cerebral vessels produces NO
      dependent increases in cerebral blood flow. Increases in cerebral blood flow
      during hypercapnia also appear to be dependent on production of NO. Astrocytes
      may release some NO constitutively, but astrocytes and microglia can release
      relatively large quantities of NO after induction of NO synthase in response to
      endotoxin or some cytokines. Expression of inducible NO synthase, perhaps in
      response to local production of cytokines, may exert cytotoxic effects in brain
      during or after ischemia. CONCLUSIONS: Because endothelium, neurons, and glia can
      all produce NO in response to some stimuli, the influence of NO on the cerebral
      circulation appears to be very important. Under normal conditions, constitutively
      produced NO influences basal cerebral vascular tone and mediates vascular
      responses to a diverse group of stimuli. The inducible form of NO synthase
      produces much greater amounts of NO that may be an important mediator of
      cytotoxicity in brain.

PMID- 7510431
TI  - Adherence of ruminant mastitis Staphylococcus aureus strains to epithelial cells
      from ovine mammary gland primary cultures and from a rat intestinal cell line.
AB  - Staphylococcus aureus isolated from mastitis (14 bovine and 11 ovine strains)
      exhibited an ability to adhere to epithelial primary cultures from ovine mammary
      gland and to a rat epithelial cell line, RIE-1. Strain differences in the degree
      of adherence were observed in both cases. These differences were maintained when
      comparing different epithelial sources (rat vs. ovine). RIE-1 cells can thus be
      used as a model for studying staphylococcal adherence to epithelial cells.
      Changes in bacterial adherence were observed according to the bacterial growth
      phase. The magnitude of these changes differed among strains. Bacterial cell
      surface hydrophobicity was not related to the degree of adherence to mammalian
      epithelial cells.

PMID- 7510432
TI  - The kinetics of human immunodeficiency virus reverse transcription are slower in
      primary human macrophages than in a lymphoid cell line.
AB  - Reverse transcription is a critical event in the life of a retrovirus and a
      potential determinant of viral infectivity. The kinetics of "endogenous"
      reactions are relatively well defined but little is known about HIV reverse
      transcription during infection. In this report, we have estimated the rate and
      efficiency of HIV-1 reverse transcription in primary macrophages and H9 lymphoid
      cells using quantitative PCR to detect intermediate cDNA structures. DNA
      synthesis is completed 12-16 hr after infection of H9 cells, but requires more
      than 36 hr in M phi, owing to slower rates of extension and template switching.
      Reverse transcription was inefficient in both cell types and in H9 cells the
      kinetics were sufficiently well resolved to estimate that only one in three
      transcripts initiated were extended to full-length viral DNA. Slower DNA
      synthesis largely accounts for the longer replicative cycle of HIV in
      macrophages. The rate of reverse transcription, which may depend upon levels of
      deoxynucleotide triphosphate substrates, is a potential factor in modulating the
      permissiveness of macrophage populations in vivo.

PMID- 7510433
TI  - Complex interactions among several nucleotide positions determine phenotypes
      defective for long-distance transport in the satellite RNA of cucumber mosaic
      virus.
AB  - Ix-satRNA is a CMV-satRNA necrogenic on tomato that is defective for long
      distance systemic movement when coinoculated in tobacco with V-TAV. To analyze
      the determinants for this defective phenotype, full-length cDNA clones of Ix
      satRNA and of the closely related, nondefective I17N-satRNA were obtained.
      Infectious transcripts from these clones (Ix5-satRNA and I17N1-satRNA) had the
      same phenotypes as the original satRNAs and differed only in four positions:
      positions 20 (Ix5, C; I17N1, U), 102 (Ix5, C; I17N1, U), 224 (Ix5, deleted;
      I17N1, A), 327 (Ix5, G; I17N1, A). By site-directed mutagenesis at positions 224
      and 327 and by recombination using two common restriction sites, satRNAs in which
      the bases at these four positions were changed from the composition at Ix5-satRNA
      to the composition at I17N1-satRNA were obtained. A comparison of the phenotypes
      of the 13 single, double, and triple mutants (respective to Ix5-satRNA) showed
      that the defective phenotype of Ix5-satRNA is determined by the nature of the
      four positions analyzed; mutants at any of the positions 102, 224, and 327
      accumulated as efficiently as I17N1-satRNA in systemically infected tobacco
      leaves when coinoculated with V-TAV. The change C20-->U also restored systemic
      movement, albeit imperfectly, giving rise to a phenotype that moved systemically
      less efficiently than I17N1-satRNA. This phenotype determined by U20 is expressed
      irrespective of the base at position 102, indicating an epistatic interaction
      between determinants 20 and 102; this interaction does not occur with position
      224 or 327. That differences in the analyzed satRNAs are due to their being able,
      or not, to move systemically is shown by the fact that all of them (including Ix5
      satRNA) accumulated to the same high level in directly inoculated leaves. The
      similarity in the sequences of the analyzed satRNAs and the complexity of the
      interactions among the effects of base changes at four positions scattered over
      the satRNA molecule suggest that the observed movement phenotypes may depend on
      conformational changes in the satRNAs.

PMID- 7510434
TI  - Assembly and extracellular release of chimeric HIV-1 Pr55gag retrovirus-like
      particles.
AB  - The HIV-1 Pr55gag precursors were previously shown to assemble and bud from a
      variety of different cell types as noninfectious virus-like particles (VLPs)
      resembling immature HIV virions. The use of these VLPs as an immunogenic and
      autologous carrier component may allow the presentation of defined epitopes
      deduced from reading frames other than gag to the immune system, thereby avoiding
      the induction of adverse immune responses. In order to identify domains within
      Pr55gag that can be replaced by immunologically relevant epitopes without
      affecting its capacity to assemble into VLPs, we deleted three domains of a
      predicted high surface probability. Deletion of amino acids 211-241 within p24CA
      and amino acids 436-471 within the p6LI portion of Pr55gag had no effect on the
      assembly, ultrastructure, biophysical properties, and yields of mutant VLPs when
      expressed via recombinant vaccinia viruses in mammalian cells. Deletion of amino
      acids 99-154 overlapping the p17MA/p24CA cleavage site completely abolished the
      capacity of the gag polyprotein to form VLPs and led to a reduction of immature
      Pr55 VLPs released into the cell-culture supernatants when coexpressed with wild
      type Pr55gag. In contrast, assembly and budding of chimeric VLPs could be
      demonstrated after replacing amino acids 211-241 and 436-471 by immunologically
      relevant epitopes derived from reading frames other than Pr55gag (e.g., V3 loop;
      CD4-binding-domain; nef-CTL epitope) or after fusion of these sequences to the
      carboxy terminus of Pr55gag. The importance of these data for the development of
      novel HIV candidate vaccines is discussed.

PMID- 7510435
TI  - Anti-idiotypic antibodies to the third variable domain of gp120 induce an anti
      HIV-1 antibody response in mice.
AB  - We tested the potential of anti-idiotypic antibodies to function as molecular
      mimics of a neutralizing epitope of the human immunodeficiency virus (HIV). Three
      monoclonal antibodies to the third variable domain (V3) of gp120 from the HIV
      1LAI isolate were raised in a BALB/c mouse. They bound gp120LAI with high
      affinity (K congruent to 10(-11) M), immunoprecipitated viral gp120LAI,
      recognized HIVLAI-infected cells by immunofluorescence and neutralized HIVLAI
      infection in vitro. Mice and rabbits were immunized against each one of these
      antibodies, and one monoclonal and two polyclonal anti-idiotypic reagents were
      selected for further study. The three anti-idiotypes recognized binding site
      related idiotopes that were not present on other V3-specific mouse sera or
      monoclonal antibodies. Groups of mice and rabbits were immunized against these
      anti-idiotypes presented in a homopolymerized form, conjugated to a protein
      carrier, or in an uncoupled form. In the absence of antigen, mice that received
      polyclonal anti-idiotypes mounted an antibody response to gp120LAI, but not to V3
      deleted gp120LAI recombinant proteins. Unlike the three nominal mAbs, the induced
      antibodies also reacted with gp120 from the divergent HIV strain SF2. The
      isotypic distribution of the anti-idiotype-induced antibodies and their temporal
      evolution resemble the restricted pattern and the rapid rise of the antibody
      response obtained after administration of recombinant gp120LAI to mice. These
      data thus present evidence that anti-idiotypes raised against HIV-specific
      antibodies may substitute viral antigens for induction of a humoral immune
      response to HIV. They also suggest that the HIV epitope variability may be, in
      part, overcome with the use of anti-idiotypic reagents.

PMID- 7510437
TI  - Uncoating of tobacco mosaic virus RNA in protoplasts.
AB  - The disassembly of tobacco mosaic virus particles during the establishment of
      infections in tobacco protoplasts was investigated by reverse transcription and
      PCR analysis of the parts of the viral RNA that remained encapsidated at various
      times after inoculation. Within the first 3 min, uncoating had proceeded from the
      5' terminus of the viral RNA to a position at least 4635 nucleotides from the 5'
      terminus. Removal of coat protein subunits from the part of the virus particle
      near the origin of assembly sequence of the RNA occurred more slowly. The results
      also suggested that progeny virus particles began to be produced 35-40 min after
      inoculation.

PMID- 7510438
TI  - The rev gene of visna virus is required for productive infection.
AB  - To assess the role of the animal lentivirus rev regulatory gene product in the
      life cycle of visna virus, we introduced mutations into the functional fourth
      exon of the rev gene of visna virus. Cultured cells transfected with a full
      length clone of visna DNA produce infectious virus but visna DNA with mutations
      in rev does not. The documented requirement for a functional rev gene in
      productive infections establishes the essential role of this gene in the
      replication of an animal lentivirus.

PMID- 7510436
TI  - Characterization and mapping of a B-cell immunogenic domain in hepatitis C virus
      E2 glycoprotein using a yeast peptide library.
AB  - To identify conserved humoral antigenic determinants within the hepatitis C virus
      (HCV) envelope protein E2, we expressed a peptide library containing random short
      fragments of the HCV envelope in yeast. Clones were identified using a
      monospecific rabbit antibody to a region downstream of the E2 hypervariable
      region. The clones define the limits of two original antigenic domains: a major
      one (aa 493-576) and a minor one (aa 535-606). The major antigenic domain maps in
      a region that displays a high degree of homology within a (HCV) subtype (92-97.6%
      identity). Yeast-encoded determinants were characterized by Western blot
      analysis, N-glycosidase F digestion, and using a panel of synthetic peptides. The
      data suggest that the major antigenic domain contains at least two determinants,
      one of them mimicked by an 18-mer peptide (aa 514-531). ELISA and competitive
      inhibition assays demonstrated that: (1) the determinants appear subtype 1a
      specific, (2) seroprevalence of antibody to the determinants is rather low
      (20.6%), and (3) donors show a heterologous response to the different
      determinants. Antibody response to the E2 determinants was studied in HCV
      infected chimpanzees and post-transfusion-associated NANB hepatitis cases. The
      antibody response was found during chronic infection and may not be effective for
      virus clearance.

PMID- 7510439
TI  - Measles virus hemagglutinin induces an Ld-restricted CD8+ cytotoxic T lymphocyte
      response to two specific epitopes.
AB  - Balb/c mice (H-2d) immunized with a vaccinia virus recombinant expressing the
      measles virus hemagglutinin (MV HA) induced a strong CD8+ cytotoxic T lymphocyte
      (CTL) response which was Ld-restricted. With reference to the predictive motif
      for Ld-restricted epitopes, a number of nonameric peptides derived from the
      primary sequence of the MV HA were tested for their ability to be restricted to
      the CTLs by P815 cells. Two peptides corresponding to amino acids 343-351 and 544
      552 of the HA primary sequence sensitized target cells for lysis by the HA
      specific CTLs.

PMID- 7510440
TI  - Identification of major antigenic domains of duck hepatitis B virus pre-S protein
      by peptide scanning.
AB  - Neutralization epitopes of duck hepatitis B virus (DHBV) have been previously
      mapped within the N-terminal portion of the pre-S protein using monoclonal
      antibodies. However, the immune response of ducks to this region is not well
      characterized at the amino acid level. To this end, we have immunized adult Pekin
      ducks with either DHBV positive serum or bacterially expressed DHBpre-S
      polypeptide representing the N-terminal portion of the DHBV pre-S region. We have
      demonstrated that adult ducks inoculated with either antigen developed antibodies
      to the DHBV pre-S region starting 5 to 10 days postinjection. The sera of all
      ducks, irrespective of the immunogen used, exhibited a significant protective
      activity against DHBV, as assessed in vivo. To identify which pre-S domains bind
      antibodies from these duck sera, we have used the Pepscan methodology with
      overlapping octapeptides spanning the DHBV pre-S sequence from amino acids 1 to
      145. Using this approach, five major antigenic domains, 7KSMDVRRI14,
      22NQLAGRMIP30, 58TLQNQGAW65, 71RRVGLSNPT79, and 127GDDPLLGNQ135 were identified
      within the DHBV pre-S region.

PMID- 7510443
TI  - Anorexia as symbolic expression of a woman's rejection of her mother's life.
AB  - Studies have failed to find consistent pathologic characteristics of mothers of
      women with anorexia nervosa. Yet the anorexic woman's perception of her mother
      remains implicated in the illness (Brumberg, 1988). Literature based on anecdotal
      and clinical reports of anorexia nervosa has questioned anorexic women's views of
      their mothers and their mothers' lives. Comparison of symptomatic and
      asymptomatic college women found that women with anorexia nervosa described more
      negative impressions of their mothers' lives. Both symptomatic and asymptomatic
      women expressed positive feelings for their mothers, but symptomatic women tended
      to say their mother's lives were perhaps fulfilling for the mothers but not
      desirable for themselves or that their mothers' lives were very difficult and
      dissatisfying for the mothers and they would not want such lives for themselves.
      Perception of maternal role model may be related to anorexia nervosa.

PMID- 7510442
TI  - Humoral immune response to the E7 protein of bovine papillomavirus type 4 and
      identification of B-cell epitopes.
AB  - We have previously vaccinated cattle with E7, the major transforming protein of
      bovine papillomavirus-4, prior to homologous virus challenge. This retarded the
      development of papillomas and promoted their early regression compared to control
      animals. To understand the mechanism for this regression, we have studied the B
      and T cell response in vaccinated animals and compared it to that of non
      vaccinated, virus-infected animals. The B cell response is reported here. The
      development of E7 IgG antibodies was detected after vaccination and before viral
      challenge, indicating that vaccine E7 is effectively presented to the immune
      system. In vaccinated animals titres of E7 antibodies remained high 10 weeks
      after viral challenge, whereas E7 antibodies in control animals were not
      detectable until 13 weeks post-viral challenge. Further analysis with synthetic
      overlapping peptides spanning the entire E7 protein mapped major immunodominant
      epitopes in the N and C termini of the protein and a minor epitope in the middle
      of the protein.

PMID- 7510441
TI  - Exogenous nucleosides promote the completion of MoMLV DNA synthesis in G0
      arrested Balb c/3T3 fibroblasts.
AB  - We studied Moloney murine leukemia virus replication in newly infected Balb c/3T3
      cells brought to the G0 phase by serum depletion. Using the polymerase chain
      reaction method, we showed that Moloney murine leukemia virus can be efficiently
      internalized in nonproliferating fibroblasts, although reverse transcription of
      the viral RNA in these cells remains incomplete. It seems likely that a lower
      availability of deoxyribonucleotides in G0-arrested cells is responsible for this
      premature termination of the reverse transcription step. Accordingly, the
      addition of high concentrations of nucleosides to the culture medium of
      nondividing cells simultaneously with infection enables them to complete the
      reverse transcription process, without re-initiating the cell cycle. Inhibition
      of reverse transcription by hydroxyurea confirms the dependence of this
      retroviral step on the intracellular nucleotide pool rather than on the precise
      arrest point of the host cell cycle. Furthermore, the pyrimidine nucleotide pool,
      and more particularly the cytidine pool, appears to play a central regulatory
      role in this step.

PMID- 7510444
TI  - Comparative study of hepatitis C virus antibody between hemodialysis and
      continuous ambulatory peritoneal dialysis patients.
AB  - We have done cross sectional and prospective studies to determine the prevalence
      and the clinical significance of antibodies to the hepatitis C virus (Anti-HCV)
      in 54 hemodialysis (HD) patients and 227 continuous ambulatory peritoneal
      dialysis (CAPD) patients. Fifteen patients (27.8%) were anti-HCV (+) among the HD
      group, and twelve patients (5.3%) were anti-HCV (+) among the CAPD group. In the
      HD group, the positivity of anti-HCV correlated with the duration of HD, but
      there was no significant correlation with the history of transfusion, the amount
      of transfusion and abnormal alanine aminotransferase (ALT). At the follow-up
      study in 164 cases (HD 50 cases, CAPD 114 cases) after 6 months, one of 14 anti
      HCV (+) CAPD patients was converted to anti-HCV (-) and two of 35 anti-HCV (-) HD
      patients were converted to anti-HCV (+). In conclusion, the prevalence of anti
      HCV was significantly higher in HD patients compared to CAPD patients, and the
      positivity for anti-HCV in HD patients correlated with the duration of HD. A
      regular follow-up of anti-HCV and isolation of anti-HCV (+) HD patients with a
      separate machine may be needed to prevent the transmission of the hepatitis C
      virus during hemodialysis.

PMID- 7510445
TI  - Identification and classification of different isolates of Francisella
      tularensis.
AB  - The causative agent of tularemia, Francisella tularensis, occurs in two main
      biovars, the highly virulent F. t. biovar tularensis, found in North America; and
      the less virulent biovar palaearctica, found all over the northern hemisphere.
      Two other biovars have been proposed, F. t. biovar mediaasiatica and F. t. biovar
      palaearctica var. japonica. In Sweden tularemia is most frequently observed in
      man and varying hares (Lepus timidus), and occasionally in other species.
      Tularemia in hares is normally an acute fatal disease, although less fatal
      infections have been reported. The diagnosis of tularemia is routinely based on
      immunological reactions. We studied 10 different isolates of F. tularensis from
      varying hares, one isolate from an Ural owl (Strix uralensis), one vaccine
      strain, one strain of F. t. biovar japonica, and six isolates from a virulence
      study of F. tularensis, by biochemical tests and by hybridization experiments
      with probes complementary to 16S rRNA. All isolates, except the isolate F. t.
      biovar japonica, were characterized as F. t. biovar palaearctica by biochemical
      tests. In the 16S rRNA analysis all isolates were positive to the probe for
      Francisella tularensis and the probe for F. t. biovar palaearctica with the
      exception that F. t. biovar japonica reacted with the probe specific to F. t.
      biovar tularensis. To further confirm that the strains used belonged to F. t.
      biovar palaearctica virulence tests in rabbits were performed which disclosed
      this phenotype. The results presented in this work show that the isolated strains
      from the western part of Europe were F. t. biovar palaearctica, irrespective of
      animal origin or virulence.

PMID- 7510446
TI  - Peripheral blood stem cell transplantation.

PMID- 7510447
TI  - Clinical experiences and biochemical findings with tacrine (THA).
AB  - A clinical comparison of tacrine (THA) and placebo was performed in 15 Alzheimer
      patients using a double blind crossover technique over 4 plus 4 weeks with one
      drug-free week in between. Treatment results, as evaluated by clinical rating
      scales and neuropsychological tests, were mostly negative. Side effects were few,
      except for elevation liver enzymes which occurred in one third of the patients.
      CSF levels of the monoamine metabolites HVA and 5-HIAA increased on tacrine as
      evidence for activation of dopamine and serotonin pathways through cholinergic
      receptors. Pharmacokinetic investigations showed that the oral bioavailability of
      tacrine was low and greatly varying between subjects. Patients with high
      bioavailability of the drug tended to improve more, and also to have more liver
      enzyme elevations, than those with low bioavailability. A gel preparation for
      rectal administration was manufactured for comparison of plasma levels attained
      during one week's treatment with levels attained with oral capsules. Preliminary
      results indicate that the dose of tacrine can be reduced to 50 per cent when
      administered rectally, probably as by this route the rapid first-pass metabolism
      of the drug in the liver is diminished. A clinical trial of tacrine via the
      rectal route would be justified as this could decrease the number of patients
      with liver side effects and increase the number of patients improving on the
      treatment.

PMID- 7510449
TI  - Induction of nasal and nasopharyngeal tumours in Sprague-Dawley rats fed with
      Chinese salted fish.
AB  - Epidemiological studies have implied that Chinese salted fish is a human
      nasopharyngeal carcinogen. In the present study, 162 Sprague-Dawley rats were
      randomly assigned to one of four experimental groups. Rats in groups 1 (n = 41)
      and 3 (n = 40) were exposed to salted fish from birth through the breast feeding
      period by giving the maternal rats a diet containing 10% and 5% salted fish,
      respectively, later feeding the rats with pellets containing 10% and 5% of salted
      fish respectively. In group 2, the rats (n = 41) were given pellets containing
      10% of salted fish from 6 weeks of age. Rats in group 4 (n = 40), serving as
      controls, were only given ordinary pellets. Three rats had nasopharyngeal
      tumours, 2 from group 1 had a poorly differentiated carcinoma and a squamous cell
      carcinoma. One rat from group 2 had a squamous cell carcinoma. Four rats had
      nasal tumours, one fibrosarcoma and one adenocarcinoma were found in rats from
      group 1. One rhabdomyosarcoma was found in group 2, and one soft tissue sarcoma
      was found in a rat in group 3. No nasal or nasopharyngeal tumours appeared in the
      control group. The difference in the occurrence of malignant nasal and
      nasopharyngeal tumours among the four experimental groups was statistically
      significant (one tailed p for trend = 0.041). The frequency of tumours appearing
      in other organs such as the breast, kidney, lung, liver and brain was not
      significantly different between the salted fish treated groups and the control
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510448
TI  - Expression of ICAM-1 on isolated human nasal, auricular and costal chondrocytes.
AB  - Expression of intercellular adhesion molecule-1 (ICAM-1) on targets has been
      reported to be a relevant factor for leukocyte migration, adhesion and function.
      Because stimulated chondrocytes have been shown to express molecules of
      immunological import (like HLA class II antigens) and because rejected or
      resorbed cartilage grafts used in the field of ENT are often characterized by
      adjacent infiltrating leukocytes, the presence of ICAM-1 on human nasal,
      auricular and costal cartilage was investigated. For this study, cartilage tissue
      sections and chondrocytes in suspension as well as cultured chondrocytes were
      prepared. Specific monoclonal antibodies (mAb) were used for immunocyto- and
      immunohistochemical Alkaline-Phosphatase-anti-Alkaline-Phosphatase staining
      (APAAP staining) as well as for flow cytometry analysis. ICAM-1 on healthy
      cartilage tissue sections was not found. On the other hand, both chondrocytes
      freed from matrix and cultured chondrocytes showed strongly positive staining
      patterns for ICAM-1. This result was obtained for chondrocytes from nasal,
      auricular as well as costal cartilage. This observed expression of ICAM-1 on
      chondrocytes with defective extracellular matrix demonstrates that cartilage
      cells are able to synthesize ICAM-1 without any paracrine stimulus from non
      chondrocyte cells. It suggests that ICAM-1 plays a role in processes where tissue
      damage leads to the exposure of chondrocyte surfaces. Therefore, ICAM-1
      expression on chondrocytes may also be a factor in destructive cartilage graft
      resorption.

PMID- 7510450
TI  - [Initial chemotherapy followed by orchiectomy and retroperitoneal lymphadenectomy
      -a case of seminoma with a testicular tumor and enlarged regional lymph nodes].
AB  - A 43-year-old male visited our hospital with complaints of right scrotal swelling
      and lower abdominal mass. Computed tomographic (CT) scan showed the right
      testicular tumor and regional enlarged lymph nodes. However, there were no
      metastasis in lung, brain, liver, and bone. First, we performed chemotherapy of
      modified PVB regimen (cisplatinum, vinblastine, peplomycin) prior to the right
      orchiectomy, because a tumor lump was palpable from the right testis to the lower
      abdominal mass. After three courses of modified PVB chemotherapy, beta-HCG, HCG
      and LDH values became within normal limits and all tumors were necrotic on the CT
      scan. Then, we performed the right orchiectomy and retroperitoneal
      lymphadenectomy simultaneously. After operation, two courses of VIP chemotherapy
      (etoposide, ifosfamide, cisplatinum) were performed since viable cells in one of
      the obturator lymph nodes were pathologically noticed. The patient has been free
      of recurrence of the tumor for 15 months after the treatment. In the particular
      case, in which the primary testicular tumor was not extirpated en bloc, the
      initial chemotherapy followed by orchiectomy was found to be feasible.

PMID- 7510451
TI  - [Ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation
      for refractory testicular cancer].
AB  - This is a report of 45-year-old man with advanced nonseminomatous germ cell tumor
      (stage IIIB2: embryonal carcinoma, yolk sac tumor, seminoma), who had relapse
      after PVB (cisplatin, vinblastine, bleomycin) chemotherapy. Peripheral blood stem
      cells (PBSCs) were taken by two consecutive apheresis using a CS-3000 blood
      separator after high-dose chemotherapy of cytarabine and mitoxantrone. In total,
      6.4 x 10(5)/kg of granulocytic cells (CFU-GM) was collected. He was treated with
      ultra high-dose chemotherapy consisting of carboplatin (800 mg/m2), etoposide
      (1,000 mg/m2) and cyclophosphamide (100 mg/kg) from day 1, followed by peripheral
      blood stem cell autotransplantation (PBSCT) on day 9. We transfused 2.4 x
      10(5)/kg CFU-GM, which was enough number of stem cells for safe PBSCT. No serious
      side effects or complications were encountered. The patient achieved partial
      remission for more than two months. However, he died of respiratory dysfunction
      caused by metastatic lung cancer 5 months later. It was thought that ultra high
      dose chemotherapy with PBSCT might be a new therapy for refractory testicular
      cancer.

PMID- 7510452
TI  - Effect of calcium antagonists on RNA synthesis of NIH 3T3 cells.
AB  - Calcium antagonists have been shown to induce a decrease in peripheral vascular
      resistance as well as a decrease in synthesis of vascular-wall matrix proteins.
      It has been shown previously that calcium antagonists decrease RNA synthesis of
      cultured, vascular, smooth-muscle cells. Here, these findings are extended to the
      investigation of whether calcium antagonists produce their vascular effects
      through their action on vascular, smooth-muscle cells only or whether they
      regulate fibroblast cells as well. It is demonstrated that in a concentration
      dependent manner verapamil, diltiazem, and nifedipine each induced a decrease in
      RNA synthesis of quiescent and serum-stimulated NIH 3T3 cells, a fibroblast cell
      line shown to express voltage-dependent Ca2+ channels. Verapamil and nifedipine
      (10(-5)M) and diltiazem (10(-4)M) caused a marked decrease of basal and serum
      induced increase in [3H]uridine uptake of NIH 3T3 cells. This is the first report
      to demonstrate that calcium antagonists have a direct effect on a fibroblast cell
      line leading to a decrease of RNA synthesis. Such findings suggest that calcium
      antagonist vascular effects extend beyond vascular smooth muscle cells to
      connective tissues associated with extracellular-matrix protein production.

PMID- 7510454
TI  - Experimental Sertoli cell tumors in the mouse and their progression into a mixed
      germ cell-sex cord proliferation.
AB  - Males of transgenic families where the large T protein of polyoma virus is
      expressed in the seminiferous epithelium of the testis (Sertoli and germ cells)
      develop bilateral testicular tumors when they become old (15 to 18 months). The
      histological features of these tumors revealed a neoplastic proliferation of
      Sertoli cell origin. Occasional isolated germ cells arrested at premeiotic stages
      were seen in the tumor. They did not participate in tumoral proliferation and
      their malignant character could not at first be established. Tumor cells injected
      in athymic (nu/nu) mice generated secondary tumors. In this case, a proliferative
      component of non-Sertoli origin was clearly evident. Its ultrastructural
      characteristics and the expression of genes that are transcribed in vivo in male
      germ cells (c-kit, LDH-X, and Hox a-4) suggest the progression of an initial,
      apparently pure Sertoli cell tumor into a mixed proliferation.

PMID- 7510453
TI  - Chronic ocular ischemia associated with the Eisenmenger's syndrome.
AB  - We studied the ocular findings of two adult patients with the Eisenmenger's
      syndrome who had atrial septal defects that were diagnosed before the age of 10
      years but not operated on and pulmonary hypertension. Both eyes of these patients
      showed microaneurysms, multiple small blot hemorrhages, or capillary dilation in
      the temporal peripheral fundus. Multiple microaneurysms and retinal collaterals
      were confirmed by fluorescein angiography. One of the patients developed
      bilateral rubeosis iridis with slow progression. These retinal lesions and the
      rubeosis iridis are probably related to chronic ocular ischemia caused by chronic
      systemic hypoxia.

PMID- 7510455
TI  - Langerhans' cell histiocytosis: expression of leukocyte cellular adhesion
      molecules suggests abnormal homing and differentiation.
AB  - Langerhans' cell histiocytosis (LCH) is characterized by an accumulation of cells
      with a Langerhans' cell (LC) phenotype. Most patients present with solitary skin
      or bone lesions, but multi-organ lesions may appear. Twenty-two LCH-tissue
      sections from 13 children and adolescents, with lesions at different sites, were
      investigated for the expression of leukocyte cellular adhesion molecules.
      Surprisingly, the LCH cells showed expression for CD2 in 11 lesions. Staining of
      LCH cells for CD11a and CD11b was positive in six and three lesions,
      respectively. Staining for CD11c, CD44, CD54, and CD58 was found consistently
      positive in all lesions. The strong reactivity for CD54 (intercellular adhesion
      molecule-1) and CD58 (leukocyte function antigen-3) is in contrast with the
      epidermal LC. LCs in culture are known to up-regulate the expression of CD54 and
      CD58. These changes are thought to reflect the in vivo situation during migration
      of activated LCs from the skin to the draining lymph node. It can be concluded
      that the abnormal cells in LCH not only share characteristics with the epidermal
      LC, but have additional characteristics of the activated LC, a cell capable of
      migration. The presumed immunological dysregulation in LCH may affect the
      expression of cellular adhesion molecules, reflected by the inconsistent
      expression of CD11a and CD11b and the unexpected expression of CD2. These
      features may contribute to migration of LCs to aberrant sites in combination with
      abnormal persistence and proliferation.

PMID- 7510457
TI  - Role of selectins in local and remote tissue injury following ischemia and
      reperfusion.
AB  - Ischemia (4-hour) followed by reperfusion (4-hour) of rat hind limbs results in
      local injury as well as remote (lung) injury. It has recently been shown that
      injury in this model is neutrophil- and cytokine-dependent and requires the beta
      2 integrin adhesion molecules CD11a/CD18 and CD11b/CD18. The role of selectins in
      events leading to injury (as determined by leakage of albumin and by hemorrhage)
      was assessed either through the use of blocking antibodies to L-, E- or P
      selectins or by the use of oligosaccharides that are reactive with selectins.
      Lung injury was found to be L- and E-selectin-dependent. When the ischemia and
      reperfusion times were reduced, lung injury was also found to be P-selectin
      dependent. In the case of hind limb injury involving the crural muscle mass,
      injury was L-selectin-dependent but independent of requirements for P- and E
      selectin. Injury in both organs was blocked by the infusion of sialylated Lewis
      pentasaccharide, whereas sialyl-N-acetyllactosamine pentasaccharide failed to
      protect against injury. In general, when selectin-blocking approaches were
      protective, there were parallel reductions in tissue content of myeloperoxidase.
      These data underscore the role of selectins in ischemia-reperfusion injury and
      suggest that selectin requirements may vary with the vascular bed under study.

PMID- 7510456
TI  - In situ detection of activated cytotoxic cells in follicular lymphomas.
AB  - The presence of cytotoxic cells and their activation status were analyzed in
      tissue sections of 26 follicular lymphomas. To this end, expression of the
      perforin and granzyme B genes was studied by in situ hybridization experiments,
      and expression of the TIA-1 antigen was analyzed by immunohistochemistry. Cells
      expressing the granzyme B gene and the perforin gene were detected in all cases.
      Their density was, however, highly heterogeneous from case to case, ranging from
      160 to 7,040 positive cells/cm2 of tissue sections. TIA-1-positive cells were
      also evidenced in the 10 follicular lymphomas tested. Virtually all cytotoxic
      cells were located in interfollicular areas. Double labeling immunochemical
      experiments showed that most cytotoxic cells belonged to the CD8+ T lymphocyte
      population, although few CD4+ T lymphocytes and CD56+ natural killer cells also
      expressed the TIA-1 antigen. These findings show that development of a malignant
      B lymphocyte proliferation is associated with a host-derived immune response
      involving intratumoral cytotoxic T lymphocytes. Further studies comparing the
      density of such cells with the final outcome are required to determine whether
      the intensity of this immune response has a prognostic value.

PMID- 7510458
TI  - Basement membrane chondroitin sulfate proteoglycan alterations in a rat model of
      polycystic kidney disease.
AB  - Alterations in basement membrane components, notably proteoglycans, in a rat
      model of polycystic kidney disease have been investigated. Rats were fed phenol
      II (2-amino-4-hydroxyphenyl-5-phenyl thiazole) for 4 days and then changed to
      normal diet for a 7-day recovery period. Marked dilation of distal tubules and
      collecting ducts was observed by 4 days with phenol II treatment, but the
      morphology returned to normal after 7 days of subsequent normal diet. Staining of
      tissue sections with two mouse monoclonal antibodies to a recently described
      basement membrane chondroitin sulfate proteoglycan (BM-CSPG) core protein was
      markedly diminished in the basement membranes of dilated cystic tubules.
      Reduction in staining was evident as early as 2 days. During recovery, BM-CSPG
      increased in tubular basement membranes and returned to normal after 7 days.
      Staining with a polyclonal antibody to chondroitin sulfate chains confirmed these
      changes in cystic tubule basement membranes. During the recovery stage,
      interstitial chondroitin sulfate (representing a CSPG other than BM-CSPG) was
      greatly increased around these tubules, along with the glycoprotein fibronectin.
      Staining with antibody to a basement membrane heparan sulfate proteoglycan core
      protein related to perlecan did not diminish but rather stained affected tubules
      intensely, whereas laminin, on the other hand, was apparently diminished in the
      basement membranes of the cystic tubules. Type IV collagen staining did not
      change through disease onset or recovery. These results suggest that BM-CSPG,
      which was rapidly altered in distribution through the onset and recovery phases,
      may be a sensitive marker of the cystic state, and in addition, the expression of
      basement membrane proteoglycans may be specifically and separately regulated in
      this disease.

PMID- 7510459
TI  - The use of a visual aid to check anaesthetic machines. Is performance improved?
AB  - We asked 20 anaesthetists and seven operating department assistants to check
      three anaesthetic machines 'doctored' to contain errors of varying seriousness,
      and recorded their performances. Two weeks later we asked the same group to
      repeat the test. On the second occasion they followed a visual aid and filled in
      a questionnaire about the test. Participants showed a significant improvement in
      the rate of fault detection when using the aid (p < 0.05). The visual aid was
      most useful at increasing the detection rate of machine leaks. Of the
      participants, 60% considered that the visual aid was helpful and 74% thought that
      such an aid should be available in our theatre complex. Sixty-six percent of
      those questioned felt that a formal check list would be of use.

PMID- 7510460
TI  - Actin in stratified squamous keratinized epithelium.
AB  - Actin filament distribution patterns were revealed in a stratified squamous
      keratinized epithelium using phalloidin-fluorescent and immunogold labeling
      techniques applied on bovine ruminal pilar as a model tissue. In non-keratinized
      cell types, actin concentrates on the microfilament-rich cellular cortex as well
      as on cytoplasmic processes and protrusions. In cornified cells labeling is
      distributed diffusely over the amorphous cytoplasm. A constant feature in all
      cell types is plasmalemmal labeling. Desmosomes exhibit deposition on their
      plasmalemmal leaflets, the dense central stratum and plaques. Desmosomal as well
      as cytoplasmic keratin filament bundles also label for actin, the latter often in
      a cross-banded manner. These cellular distribution patterns of actin filaments
      are discussed with respect to the significance of the microfilaments in the
      process of cell shape determination, stratification, and cell adhesion.

PMID- 7510463
TI  - Carotenoids and vitamin A in prevention, adjuvant cancer therapy, mastalgia
      treatment, and AIDS-related complex.

PMID- 7510461
TI  - Immunologic studies of anaphylaxis to iron dextran in patients on renal dialysis.
AB  - Systemic reactions resembling anaphylaxis have occurred after intravenous (IV)
      iron-dextran administration, a treatment modality that has acquired increased
      acceptance following the use of erythropoietin for the anemia of patients with
      chronic renal diseases. Three such patients sustained anaphylactoid reactions
      immediately after receiving IV test doses of iron-dextran which were their only
      known exposures. In an effort to determine the mechanism of their reactions, we
      applied tests for (1) basophil degranulation by iron-dextran, basophil histamine
      release; (2) a type I anaphylactic reaction, specific IgE antibodies; and (3) an
      immune complex activation, specific IgG antibodies against iron-dextran. Six
      other patients with renal diseases served as controls, three of whom had
      tolerated IV iron-dextran, and three without known exposure. One patient only had
      any test abnormalities. Her initial positive basophil histamine release and
      specific IgG antibodies reversed and declined respectively at a 4-month follow-up
      study. She had developed anaphylaxis, and her studies had been performed at a
      time after anaphylaxis earlier than the other two. The mechanisms of iron-dextran
      anaphylaxis may be multiple and not be detectable several months after the
      incident. Prospective studies will probably be required for a predictive test to
      be developed.

PMID- 7510464
TI  - [The nucleolus organizer region (Ag NORS) in urothelial tumors. Apropos of 10
      cases].
AB  - The authors study nucleolar organisers (Ag NORS) in ten cases of urothelial
      tumours, graded as grade I in five cases, grade II in two cases, grade III in two
      cases and intermediate grade II-III in one case. Study of the NOR index showed a
      mean value of 3.89 for grade I, 4.66 for grade II, 5.88 for grade III and 4.90
      for the intermediate grade II-III. Different values were recorded in the same
      heterogeneous tumours containing tumour zones of different grades, providing an
      additional argument in favour of the heterogeneity of these urothelial tumours
      and accounting for the difficulties of their classification reported in the
      literature. Adequate sampling should allow a more objective and more
      representative study of all of the tumours examined.

PMID- 7510465
TI  - [A case of testicular cancer in which complete response was achieved with
      chemotherapy including cisplatin, etoposide and bleomycin, and salvage surgery].
AB  - A 27-year-old man was admitted with a complaint of induration of the left testis
      in August, 1992. On physical examination, he had a palpable supraclavicular mass.
      The clinical diagnosis was testicular cancer with metastases of lung field,
      cervical, mediastinal and retroperitoneal lymph node. The histological diagnosis
      made by inguinal orchiectomy was embryonal cell carcinoma with
      syncytiotrophoblastic cell. Chemotherapy with cisplatin, etoposide and bleomycin
      (BEP) was started on August 22, 1992. After 3 courses of chemotherapy, most of
      the lymph node metastases decreased in volume on CT scan with negative tumor
      markers. In an attempt to obtain surgical complete response, dissection including
      cervical, mediastinal and retroperitoneal node was performed in December, 1992.
      Pathological examination revealed no viable cells in all sections. He is alive
      with no evidence of disease on September 8, 1993.

PMID- 7510462
TI  - Antigen (DNP-As)-induced allergic rhinitis model in guinea pigs.
AB  - In guinea pigs, an IgE antibody was produced by intraperitoneal injection of
      antigen (DNP-As) containing Al(OH)3 and booster inhalation of the antigen into
      the nasal cavity. Experimental allergic rhinitis was induced by the perfusion of
      antigen solution into the nasal cavities of actively sensitized guinea pigs.
      Severity of allergic rhinitis was assessed by determining release of histamine
      and leakage of dye into the nasal cavity. The antigen-induced release of
      histamine was significantly increased at 0 to 15 minutes following antigen
      administration but then decreased with time. The antigen-induced leakage of dye
      was sustained for 60 minutes after administration of the antigen. These results
      suggest that the DNP-As-induced allergic rhinitis model in guinea pigs is
      instrumental in evaluating the effect of various factors on allergic rhinitis.

PMID- 7510466
TI  - Effects of interleukin-1 beta on insulin-like growth factor-I autocrine/paracrine
      axis in cultured rat articular chondrocytes.
AB  - OBJECTIVE: To clarify the interaction of tissue destruction and repair of
      articular cartilage during inflammation, the effects of interleukin-1 beta (IL-1
      beta) on the expression of insulin-like growth factor I (IGF-I), its receptor,
      and its binding proteins were examined. METHODS: Articular chondrocytes from five
      week rats were cultured in serum free medium treated with IL-1 beta (1-100 U/ml)
      for 24 hours. The concentration of IGF-1 in the conditioned medium was measured
      by RIA, and IGFBP were analysed by immunoligand blotting method. IGF-I receptors
      were also examined by [125I]IGF-I binding study. RESULTS: IL-1 beta induced the
      secretion of IGF-I and IGF-binding protein in chondrocytes; this was not
      inhibited by indomethacin (5 micrograms/ml). IL-1 beta also increased the number
      of IGF-I receptors but had no effect on receptor affinity. IL-1 beta inhibited
      chondrocyte proliferation, while exogenous IGF-I and growth hormone stimulated
      chondrocyte cell growth. IL-1 beta did not change IGF-I mRNA levels. CONCLUSION:
      IL-1 beta up-regulated the IGF-I autocrine/paracrine axis in cultured articular
      chondrocytes. These observations provide insight into the critical role played by
      IL-1 beta in tissue destruction and repair, and into the direct interaction
      between cytokines and growth factors associated with inflammatory arthropathy.

PMID- 7510468
TI  - [Sodium intake and angiotensin in hypertension induced by chronic NO synthase
      inhibition in the rat].
AB  - The influence of dietary sodium restriction and angiotensin II blockade on
      hypertension induced by a 25-day period of administration of the inhibitor of
      nitric oxide synthesis NG-nitro-L-arginine methyl ester (L-NAME: 10 mg/kg twice
      daily by gavage) was assessed in Wistar rats fed a normal or low sodium diet. In
      addition, the angiotension II receptor blocker, losartan (30 mg/kg once daily by
      gavage) was administered prior to and during L-NAME in rats fed the normal sodium
      diet. Results expressed as mean +/- ESM are presented in the following table:
      [table: see text] At the end of studies, conscious systolic arterial pressure
      increased similarly in L-NAME-treated groups maintained on NS or LS intake.
      Moreover, a 25% reduction in cardiac output due to a decrease in stroke volume
      was observed in both groups. A slight but significant cardiac hypertrophic
      response was observed in hypertensive rats irrespective of sodium intake.
      Losartan totally prevented the development of hypertension as well as the
      decrease in cardiac output and the cardiac hypertrophy associated with L-NAME
      treatment in rats on normal sodium intake. In conclusion, hypertension resulting
      from chronic blockade of nitric oxide synthesis was not affected by dietary
      sodium restriction. A crucial role for the renin-angiotensin system was
      demonstrated in this new model of hypertension.

PMID- 7510469
TI  - How it began.

PMID- 7510467
TI  - [Vasodilator effect of nitric oxide is a necessary counter-regulation in the
      spontaneously hypertensive rat].
AB  - The chronic inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L
      NAME, a L-arginine analogue) induces a dose-dependent decrease in aortic cGMP and
      an increase in blood pressure. We used this pharmacological approach to evaluate
      the release of NO in vivo in spontaneously hypertensive rats (SHR); 15 SHR and 10
      Wistar-Kyoto rats (WKY) were given 25 mg L-NAME/kg/d by gavage for 15 days; 10
      SHR and 10 WKY rats given water for the same period were used as control. During
      the trial, 10/15 SHR given L-NAME died. Systolic blood pressure (mmHg) increased
      from 132 +/- 6 to 170 +/- 4 in WKY given L-NAME and from 169 +/- 4 to 242 +/- 6
      in SHR given L-NAME. Aortic cGMP content (fmol/mg protein) was 2,204 +/- 382 and
      2,076 +/- 461 fmol/mg control WKY and SHR (NS), and was decreased to 324 +/- 44
      and 641 +/- 70 in WKY and SHR given L-NAME respectively (p < 0.0001 each). L-NAME
      increased plasma atrial natriuretic factor only in SHR. In summary, basal aortic
      cGMP content, reflecting the basal release of NO, was similar in WKY and SHR. The
      decrease in aortic cGMP content of SHR given L-NAME, due to the blockade of NO
      synthase, was accompanied by a large increase in systolic blood pressure and a
      tremendous mortality rate. Thus, basal release of NO is probably not impaired in
      SHR, but represents a major counterregulatory mechanism in this genetic model of
      arterial hypertension.

PMID- 7510470
TI  - A new approach to chronic viral disease therapy by cytokines.
AB  - Eradication of an infectious agent during the acute phase of infection is a
      complicated process which involves several specific and non-specific mechanisms
      of the immune system. In chronic diseases, one of these steps may be missing or
      impaired which results in a malfunctions of the whole system and prolonged
      presence in the host invading pathogen. Mentioned above mechanisms are governed
      by cytokine network. Released by activated cells--cytokines initiate cascade
      reactions leading to eradication of pathogen. For practical purposes a model was
      formulated which resembles an electronic computer. In this model cytokines
      represent signals or words which when combined together form more or less precise
      instruction how to repair damages done by invading pathogen. Cells receiving
      cytokine signals become activated and transform messages increasing sometimes
      intensity of signals or release new ones which may initiate additional reactions.
      To activate full reaction two independent signals are required. Full activation
      of the eradication mechanisms requires activation of different types of cells. To
      achieve this goal proper combination of signals generated by cytokines should be
      induced. Efficacy of cytokines therapy may depend upon several factors such as
      route of administration, composition of cytokines, dose and modality of delivery.
      In the biological computer model introduction of cytokines on the surface of
      epithelium of the oral cavity in minute quantities and in proper composition
      should give the best clinical therapeutic results.

PMID- 7510471
TI  - Inhibition of human immunodeficiency virus type 1 replication by human
      interferons alpha, beta and gamma.
AB  - The effect of various preparations of human interferon (HuIFN) upon human
      immunodeficiency virus (HIV-1) replication in cell lines and primary cultures of
      peripheral blood lymphocytes (PBL) was investigated. Natural interferon alpha
      (nHuIFN-alpha) exhibited a much higher inhibitory effect upon HIV-1 replication
      than did recombinant HuIFN-alpha (rHuIFN-alpha).

PMID- 7510472
TI  - Behaviour of chosen acute phase proteins in acute viral type B hepatitis as a
      predictive factor of further evolution of the infection.
AB  - The study was aimed at the assessment of the immune system function of a large
      group of patients with early phase of acute viral type B hepatitis, who were
      subsequently follow-up in order to select those developing chronic forms of the
      infection. It was assumed that re-assessment of their initial immunological
      status with regard to further evolution of the infection would show some factors
      predictive of chronic active hepatitis development. Chosen immunological
      parameters: circulating blood lymphocyte sets and subsets, immunoglobulin
      concentrations, presence of non-specific immune complexes and concentrations of
      randomly chosen acute phase proteins (ceruloplasmin, transferrin, haptoglobin,
      alpha-acid glycoprotein, C3 and C4 complement components) were evaluated in 104
      acute viral type B hepatitis patients, aged 18-50, on the days 8, 10, 15, 30, 40,
      60, 80 and 130 of the illness. After mean of 744 days, 56 patients reported to
      final follow-up examination, 15 of whom presented with symptoms of chronic
      sequelae of acute HBV infection (elimination phase of chronic aggressive
      hepatitis, chronic persistent hepatitis, or integration phase of HBV infection).
      Behaviour of cellular immunity parameters, immunoglobulin concentrations,
      presence of immune complexes or non-specific antibodies, however varied in
      individual patients, showed no correlation predictive of chronic sequelae of the
      infection. Significant differences between patients who subsequently developed
      chronic active or chronic persistent hepatitis were found, however, with regard
      to all the acute phase proteins tested, most prominent in case of C3 and C4
      complement components, haptoglobin, transferrin and ceruloplasmin.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7510473
TI  - Specific detection of positive and negative stranded hepatitis C viral RNA using
      chemical RNA modification.
AB  - Since hepatitis C virus (HCV), a major causative agent of posttransfusional non
      A, non-B hepatitis, is a positive stranded RNA virus, it is supposed to replicate
      via a negative RNA strand. Although strand specific reverse transcription
      polymerase chain reaction (RT-PCR) method was recently developed to detect each
      strand of HCV RNA, the specificity of the strategy has remained to be determined.
      In this study, using in vitro transcribed positive and negative stranded HCV RNAs
      mixed with hepatic cellular RNA from normal liver, we found that this strategy
      did not distinguish between the two RNA strands, but that chemical modification
      of RNA samples at the 3' end followed by strand specific RT-PCR made specific
      detection possible. Liver tissues, sera and peripheral blood mononuclear cells
      (PBMC) from ten patients with chronic HCV infection were analyzed with the novel
      strategy of RT-PCR combined with RNA modification. Positive and negative strands
      of HCV RNA were detected in liver tissues of ten (100%) and nine (90%) cases,
      respectively. Negative RNA strand was detected also in sera of five cases (50%),
      positive strand being detected in nine cases (90%). In PBMC, positive strand of
      HCV RNA was detected in eight cases (80%), whereas negative strand in only one
      case (10%), suggesting that HCV has much less cellular tropism to PBMC than to
      hepatocytes.

PMID- 7510475
TI  - The affinities of monoclonal antibodies against core antigen of hepatitis B
      virus.
AB  - Four monoclonal antibodies generated against the recombinant core antigen of
      hepatitis B virus are investigated for antigen binding. All exhibit a similar
      affinity to polystyrene-sorbed antigen but only one of them interacts with native
      form of HBcAg (an assembled particle) in solution. The presence of 0.1% sodium
      dodecylsulphate is required for the binding of other three antibodies. The
      phenomenon can be interpreted as inaccessibility of the corresponding epitopes
      unless the multimeric antigen structure is disrupted. The core antigen coated on
      polystyrene is considered as a similar exposed structure.

PMID- 7510474
TI  - The X-gene of human hepatitis B virus transactivates the c-jun and alpha
      fetoprotein genes.
AB  - The X-gene product of human hepatitis B virus is a transacting transcriptional
      factor which activates a variety of heterologous viral and host
      promoters/enhancers. We have found that the X-gene product can significantly
      transactivate the regulatory sequences located at the 5'-upstream of the c-jun
      oncogene when a reporter plasmid containing the sequences was co-transfected to
      HepG2 cells with an X-gene expression plasmid. The results of mutational analysis
      indicate that the X-gene activation requires the AP-1 sequence of the c-jun gene.
      Furthermore, we also found that the X-gene is capable of activating the 5'
      upstream sequence of the alpha-fetoprotein gene. There are at least two elements
      that respond to the X-gene transactivation. One is located in the sequences
      between -5,100 and -2,900, and the other is at the C/EBP site. Therefore, the X
      gene activates the c-jun and alpha-fetoprotein genes through different host
      factors, namely AP-1 and C/EBP, respectively. The results of c-jun activation by
      the X-gene strongly support the previous hypothesis that the X-gene may play a
      critical role in the development of hepatocellular carcinoma.

PMID- 7510476
TI  - [Immune response against protein epitopes modified with acetaldehyde and its
      clinical significance in alcoholic liver diseases].
AB  - Acetaldehyde, the first metabolite of ethanol, is capable to bind various
      proteins followed by the formation of acetaldehyde adducts. This condensate is
      supposed to act as a neoantigen. We have recently demonstrated the appearance of
      acetaldehyde adducts in liver of experimental animals after chronic ethanol
      treatment, and we produced an experimental hepatitis in guinea pig by
      immunization with acetaldehyde adducts and treatment with free access to ethanol.
      However the structure of acetaldehyde adducts and its characteristics are still
      vague. To elucidate the binding site of anti-adducts antibody against the epitope
      on adducts, we established a cell line of hybridoma producing monoclonal
      antibody. This monoclonal antibody recognized protein condensate modified with
      high concentration of acetaldehyde (1-10 mM) but not those modified with low
      concentration of it (20-200 microM), whereas the polyclonal antibody produced by
      conventional method recognized both of them. Using the affinity-purified adducts
      by monoclonal or polyclonal antibody-liganded column, we examined the antibody
      titers by ELISA. The elevation of antibody titer was more specific in chronic
      alcoholics, especially in patients with hepatic inflammatory change, when
      antibody was measured against the adducts purified by monoclonal antibody than
      against the adduct purified by polyclonal antibody. Namely, there exist different
      types of antibody according to the concentration of acetaldehyde to form the
      adducts. The concentration of acetaldehyde is thought to be much greater in the
      liver of alcoholics compared to the patient with non alcoholic liver disease.
      Actually we have immunohistochemically detected the adduct related to high
      concentration of acetaldehyde in the liver specimen of alcoholics. In conclusion,
      the appearance of adduct related to high concentration of acetaldehyde and the
      acquisition of immunity against it appear to be a characteristic feature in
      alcoholics with hepatic inflammation. Therefore, evaluation of circulating
      antibodies against protein epitope related to high concentration of acetaldehyde
      is helpful to know conditions of such types of liver disease seen in alcoholics.

PMID- 7510478
TI  - A conjugate of lactosaminated poly-L-lysine with adenine arabinoside
      monophosphate, administered to mice by intramuscular route, accomplishes a
      selective delivery of the drug to the liver.
AB  - A conjugate of the antiviral agent adenine arabinoside monophosphate (ara-AMP)
      with a low molecular mass lactosaminated poly-L-lysine, administered to mice by
      i.m. route, selectively delivers the drug to the liver. In mice the conjugate is
      devoid of acute toxicity even at high dose (1.3 mg/g) and injected i.m. for 20
      days does not induce antibodies. Moreover it is highly soluble in water; this
      means that a pharmacologically active dose may be administered in a small volume
      compatible with the i.m. route. Compared to the similar ara-AMP complex with
      lactosaminated albumin which must be injected intravenously, the present
      conjugate might assure a better compliance of patients with hepatitis B virus
      infection for a long lasting, liver targeted antiviral treatment.

PMID- 7510477
TI  - Identification of targeting proteinase for rat alpha 1-macroglobulin in vivo.
      Mast-cell tryptase is a major component of the alpha 1-macroglobulin-proteinase
      complex endocytosed into rat liver lysosomes.
AB  - The alpha 1-macroglobulin-proteinase complex endocytosed into rat liver lysosomes
      was purified by a series of column chromatographic steps on concanavalin A
      Sepharose, Sephacryl S-300, DEAE-cellulose and TSK gel DEAE-5PW columns. The
      complex contained no detectable alpha 2-macroglobulin. Studies on the substrate
      specificity indicated that the complex had tryptase-like activities towards
      various synthetic substrates, but no elastase, chymotrypsin, cathepsin-B and
      cathepsin-L activities. The proteinase activity was completely inhibited by di
      isopropyl fluorophosphate, leupeptin and antipain, indicating that the proteinase
      bound to alpha 1-macroglobulin is a serine proteinase. Two protein bands (62 and
      59 kDa) of the complex were labelled with [3H]diisopropyl fluorophosphate and
      both bands cross-reacted with anti-(mast-cell tryptase)antibody. These results
      suggest that mast-cell tryptase is a major targeting proteinase for alpha 1
      macroglobulin in vivo. The main alpha-macroglobulin-proteinase complex in the
      adjuvant-treated rats was also the alpha 1-macroglobulin-tryptase complex, even
      though the plasma level of alpha 2-macroglobulin was elevated.

PMID- 7510479
TI  - Leucovorin rescue of human cancer and bone marrow cells following edatrexate or
      methotrexate.
AB  - We have examined the cytotoxic activities of edatrexate (EDX) and methotrexate
      (MTX) and their reversal by leucovorin in nine human cancer cell lines and in
      human bone marrow CFU-GM cells. EDX was 3.7- to 123-fold more toxic than MTX
      against the cancer cell lines and 25-fold against the bone marrow cells. Lower
      EDX concentrates generally were needed to inhibit cancer cell growth relative to
      bone marrow cells, however, whereas bone marrow and cancer cell growth were more
      often susceptible to the same MTX concentrations. The new antifolate was
      metabolized to long-chain polyglutamates to a greater extent than MTX in seven
      cell lines. Leucovorin at 0.2 microM rescued two breast cancer and two non-small
      cell lung cancer cell lines to a lesser extent following EDX than MTX, but
      significant rescue was observed in two head and neck cancer cell lines that
      formed large amounts of polyglutamates. These cell lines also accumulated reduced
      folates to a greater extent than the other cell lines following leucovorin
      exposure. Leucovorin rescued bone marrow cells following MTX but only partially
      following the highest EDX concentrations. EDX may enjoy a better therapeutic
      index than MTX against some cancer cell lines relative to bone marrow precursor
      cells, especially after leucovorin rescue.

PMID- 7510480
TI  - Metabolism of FK506, a potent immunosuppressive agent, by cytochrome P450 3A
      enzymes in rat, dog and human liver microsomes.
AB  - The oxidative metabolism of FK506 by liver microsomes and purified cytochrome
      P450 (P450) enzymes from rats, dogs and humans was studied. The major metabolite
      formed by liver microsomes from all species was 13-demethylated FK506, named M-I.
      In adult rats, liver microsomal metabolic activity toward FK506 was higher in
      males than in females and was stimulated by treatment with P450 3A inducers such
      as dexamethasone and phenobarbital. In a reconstituted monooxygenase system
      containing various forms of purified P450 3A enzymes, rat P450 3A2, dog P450 DPB
      1 (a form of the P450 3A family) and human P450 3A4 catalyzed FK506 oxidation
      efficiently in the presence of cytochrome b5, a mixture of phospholipids
      (dilauroylphosphatidylcholine, dioleoylphosphatidylcholine and
      phosphatidylserine), and sodium cholate. Rat P450 2C6 and 2D1 and human P450 2CMP
      also metabolized FK506, with significant lower activity than the P450 3A enzymes,
      and other rat P450 1A, 2A, 2B, 2C and 2E families including C11 did not show
      catalytic activities for FK506. Anti-P450 3A2 and anti-P450 3A4 antibodies
      strongly inhibited FK506 oxidation catalyzed by rat and human liver microsomes,
      respectively. The formation rate of M-I correlated well with testosterone 2 beta-
      and 6 beta-hydroxylase activities in rat liver microsomes and with
      immunoquantified P450 3A4 content, nifedipine oxidase activity, and testosterone
      6 beta-hydroxylase activity in human liver microsomes. These in vitro findings
      indicate that the P450 3A enzymes in liver microsomes from various species of
      animals, including human, play a major role in the first step oxidation of FK506.

PMID- 7510481
TI  - The effects of orally administered calcium pentosan polysulfate on inflammation
      and cartilage degradation produced in rabbit joints by intraarticular injection
      of a hyaluronate-polylysine complex.
AB  - OBJECTIVE: To determine the antiinflammatory and cartilage-protecting activities
      of orally administered calcium pentosan polysulfate (CaPPS) in a rabbit model of
      inflammatory arthritis. METHODS: A single intraarticular injection of a preformed
      polycation complex (PC) of poly-D-lysine and hyaluronan was used to induce joint
      inflammation; saline was injected into the contralateral joint as a control.
      Animals were killed 1, 4, 7, or 10 days post-PC injection. CaPPS, at 5 mg/kg, 10
      mg/kg, or 75 mg/kg, was given every 48 hours commencing 7 days prior to PC
      injection. Serum interleukin-6 (IL-6), synovial fluid (SF) prostaglandin E2, cell
      numbers, and cartilage proteoglycan (PG) content, composition, and biosynthesis
      were determined for PC- and saline-injected joints. RESULTS: In PC-injected, non
      drug-treated animals, serum IL-6 activity, SF leukocyte numbers, and
      prostaglandin E2 levels were elevated, while cartilage PG content and
      biosynthesis were reduced. CaPPS at 10 mg/kg, but not at 5 mg/kg, decreased serum
      IL-6 levels but maintained cartilage PG concentration and biosynthesis. However,
      SF leukocyte counts and prostaglandin E2 levels (except on day 1) were not
      reduced. CONCLUSION: The ability of CaPPS to attenuate serum IL-6 levels and
      preserve cartilage PGs in inflamed rabbit joints suggests that this substance
      could be of value as an effective orally administered chondroprotective,
      antiarthritic drug.

PMID- 7510482
TI  - Granulocyte colony-stimulating factor induction of improved leukocytopenia with
      inflammatory flare in a Felty's syndrome patient.

PMID- 7510484
TI  - The origin, sequence, structure, and consequences of developing anti-DNA
      antibodies. A human perspective.

PMID- 7510483
TI  - Increased antiretroviral antibody reactivity in sera from a defined population of
      patients with systemic lupus erythematosus. Correlation with autoantibodies and
      clinical manifestations.
AB  - OBJECTIVE: The implied role of retroviruses in the pathogenesis of murine
      systemic lupus erythematosus (SLE) led us to study antiretroviral antibodies in a
      population-based SLE cohort. METHODS: Immunoassays using whole virus and
      synthetic peptides were performed on sera from 72 patients with SLE and 88
      control subjects. RESULTS: Reactions with whole baboon endogenous virus occurred
      more frequently in patients with SLE, and correlated with the presence of anti
      RNP and anti-Sm. Some retroviral env and gag peptides, several of which were
      similar to U1 small nuclear RNP, reacted more strongly in patients with SLE, and
      their presence was correlated with discoid rash, hematologic disorder, and other
      symptoms. CONCLUSION: These results provide circumstantial evidence for
      involvement of retroviruses in the pathogenesis of human SLE; further studies
      should be carried out using other techniques for measurement of retroviral
      expression.

PMID- 7510487
TI  - Immunocytochemical localization and serologic detection of transforming growth
      factor beta 1. Association with type I procollagen and inflammatory cell markers
      in diffuse and limited systemic sclerosis, morphea, and Raynaud's phenomenon.
AB  - OBJECTIVE: To determine the presence of transforming growth factor beta 1 (TGF
      beta 1) and inflammatory cell markers (HLA-DR and Factor XIIIa) and to compare
      these with the presence of type I procollagen, in clinically uninvolved and
      involved skin from patients with different subsets of systemic sclerosis (SSc),
      and to analyze circulating levels of TGF beta 1 in SSc patients. METHODS: TGF
      beta 1, HLA-DR, Factor XIIIa, and type I procollagen were detected in skin biopsy
      sections using a biotin-streptavidin-peroxidase system. Levels of circulating TGF
      beta 1 were measured using a capture enzyme-linked immunosorbent assay technique.
      RESULTS: Patients with active diffuse cutaneous SSc (dcSSc) showed minimal TGF
      beta 1 but significant type I procollagen staining in involved skin, while the
      clinically uninvolved skin of these patients showed moderate extracellular and
      intra-epidermal TGF beta 1 immunoreactivity. Patients with limited cutaneous SSc
      (lcSSc) showed elevated TGF beta 1 staining in both involved and uninvolved skin,
      as well as procollagen staining. Significant TGF beta 1 reactivity, HLA-DR and
      Factor XIIIa immunoreactivity, numerous inflammatory cells, and procollagen
      staining were seen in specimens from patients with morphea. Sequential biopsies
      suggested the presence of cytokine activity at the earliest stages of disease,
      which was not maintained with progression of sclerosis. Among the disease groups
      studied, elevated levels of circulating TGF beta 1 were seen only in patients
      with morphea. CONCLUSION: The pattern of TGF beta 1 staining in dermal sections
      from patients with dcSSc, lcSSc, and morphea suggests that this cytokine is
      important in the pathogenesis of scleroderma. Furthermore, the presence of TGF
      beta 1 prior to the onset of fibrosis indicates an early involvement of this
      growth factor, possibly in the inflammatory stage of the disease.

PMID- 7510485
TI  - Local proliferation of fibroblast-like synoviocytes contributes to synovial
      hyperplasia. Results of proliferating cell nuclear antigen/cyclin, c-myc, and
      nucleolar organizer region staining.
AB  - OBJECTIVE: To test the hypothesis that local proliferation contributes
      significantly to the hyperplasia of rheumatoid synovium. METHODS:
      Immunohistologic and chemical staining was used to identify 3 markers of cell
      proliferation: proliferating cell nuclear antigen, c-myc proto-oncogene, and
      nucleolar organizer regions. Synovium from 21 patients with rheumatoid arthritis,
      34 with degenerative joint disease, and 7 with joint trauma was examined.
      RESULTS: All 3 markers indicated substantial, active proliferation of synovial
      lining cells in synovium with hyperplasia. Proliferating cells showed type I
      procollagen immunoreactivity but were negative for CD68, a monocyte/macrophage
      marker. Proliferation was greater in rheumatoid arthritis than in the other
      conditions evaluated. CONCLUSION: In situ proliferation of fibroblast-like
      synoviocytes in the synovium lining contributes considerably to the increase in
      cell numbers in rheumatoid synovium.

PMID- 7510486
TI  - Human osteoarthritic chondrocytes possess an increased number of insulin-like
      growth factor 1 binding sites but are unresponsive to its stimulation. Possible
      role of IGF-1-binding proteins.
AB  - OBJECTIVE: To characterize the insulin-like growth factor 1 (IGF-1) receptor in
      human osteoarthritic (OA) and normal adult chondrocytes. The biologic response of
      chondrocytes to IGF-1 stimulation was examined, as was the presence and synthesis
      of IGF binding proteins (IGFBP) in these cells. METHODS: Binding studies,
      Northern blot, immunohistochemical analysis, and affinity cross-linking
      experiments were performed for characterization of the IGF receptor, and the
      latter method was also used for IGFBP determination. The biologic response was
      estimated via the incorporation of radiolabeled proline into a newly synthesized
      protein. RESULTS: Binding experiments revealed a single class of binding sites.
      The mean +/- SEM affinity (Kd) of normal chondrocytes was 1.4 +/- 0.4 nM, with
      26.8 +/- 5.5 x 10(3) binding sites/cell. OA chondrocytes had a lower affinity (Kd
      15.4 +/- 4.7 nM) and a higher density (1,178.3 +/- 299.5 x 10(3) binding
      sites/cell) compared with normal cells (P < 0.004 and P < 0.001, respectively).
      Immunohistochemical studies with a monoclonal antibody (MAb) against the type 1
      IGF receptor (alpha IR3) showed increased staining in OA cartilage compared with
      normal tissue. Biologic responses of chondrocytes after IGF-1 stimulation
      revealed that OA chondrocytes were unresponsive, whereas a 2.5-fold increase in
      new protein synthesis was observed in normal cells. Competition studies in normal
      chondrocytes revealed that both IGF-1 and IGF-2 displaced radiolabeled IGF-1 in a
      comparable manner; however, insulin at high concentration weakly competes.
      Moreover, MAb alpha IR3 effectively blocked specific binding in normal
      chondrocytes (77%), but not in OA chondrocytes (26%). Northern blot and covalent
      cross-linking analyses revealed the specific band characteristic of type 1
      receptor. With the latter technique, other bands corresponding to the IGFBPs were
      also detected. Comparison between normal and OA chondrocytes showed increased
      intensity of the IGFBP bands, particularly those corresponding to the IGFBP-3
      doublet. CONCLUSION: It is shown that type 1 IGF receptor is expressed in human
      articular cartilage and that the level of binding sites is significantly
      increased in OA chondrocytes. Interestingly, despite the higher level of binding
      sites in OA cells, no response to IGF-1 stimulation was found in these cells. Our
      data suggest that this increase in specific binding may involve not only the type
      1 IGF receptor but also IGFBP on the cell surface. The latter, by binding the IGF
      1, will diminish the bioavailability of IGF-1 and thus prevent its anabolic
      action.

PMID- 7510488
TI  - CD4+ T cell-mediated leukopenia of Felty's syndrome successfully treated with
      granulocyte-colony-stimulating factor and methotrexate.

PMID- 7510489
TI  - Whipple's disease and granulomatous synovitis: comment on the article by
      Gravallese et al.

PMID- 7510490
TI  - CD8+, CD3+, CD57+ lymphocytes in rheumatoid arthritis: comment on the article by
      Dupuy d'Angeac et al.

PMID- 7510492
TI  - Up-regulation of endothelial cell adhesion molecules characterizes disease
      activity in systemic lupus erythematosus. The Shwartzman phenomenon revisited.
AB  - OBJECTIVE: To test the hypothesis that during exacerbations of systemic lupus
      erythematosus (SLE), endothelial cells are activated to increase their expression
      of adhesion molecules. METHODS: Endothelial cell expression of E-selectin,
      vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1
      (ICAM-1) was quantitated immunohistochemically in 20 biopsy specimens from
      nonlesional, non-sun-exposed skin from 16 SLE patients. Disease activity was
      evaluated with the SLE Disease Activity Index (SLEDAI) and with measurements of
      complement components C3a desArg, C3, and C4. RESULTS: The mean expression of all
      3 adhesion molecules was significantly elevated in patients with SLE versus
      healthy controls, as well as in patients with active versus inactive SLE. The
      mean C3a desArg level was significantly higher in patients with active SLE
      compared with those with inactive SLE. The SLEDAI scores correlated directly with
      C3a desArg levels and inversely with C3 and with C4 levels. Evaluation of serial
      biopsy specimens demonstrated loss of endothelial cell adhesion molecules and
      reduction of C3a levels with clinical improvement. CONCLUSION: Our findings
      demonstrate up-regulation of the surface expression of 3 distinct adhesion
      molecules, E-selectin, VCAM-1, and ICAM-1, in patients with SLE. The abnormal
      expression of these endothelial cell adhesion molecules is most marked in
      patients with active disease characterized by significant elevations of the
      complement split product C3a desArg. We suggest that in certain SLE patients,
      excessive complement activation in association with primed endothelial cells
      induces leukocyte-endothelial cell adhesion and leuko-occlusive vasculopathy.

PMID- 7510491
TI  - Expression of L-selectin, CD43, and CD44 in synovial fluid neutrophils from
      patients with inflammatory joint diseases. Evidence for a soluble form of L
      selectin in synovial fluid.
AB  - OBJECTIVE: To study the expression of L-selectin, CD43, and CD44 on peripheral
      blood (PB) and synovial fluid (SF) neutrophils from patients with inflammatory
      joint diseases, and to investigate the presence of soluble L-selectin in both SF
      and plasma from patients with acute and chronic arthritis. METHODS: PB and SF
      neutrophils were isolated from 13 patients with rheumatoid arthritis (RA) and 17
      patients with various inflammatory joint diseases other than RA. Expression of L
      selectin, CD43, CD44, CD11a, and CD11b was determined in both unstimulated and in
      vitro-activated cells by immunofluorescence flow cytometry. Soluble L-selectin
      levels were estimated in SF and plasma by a semiquantitative radioimmunoassay.
      RESULTS: Neutrophils from SF showed diminished expression of L-selectin compared
      with PB neutrophils; CD43 expression and CD44 expression were decreased in SF
      neutrophils from most patients. In contrast, SF neutrophils exhibited
      significantly increased expression of CD11b, to an extent similar to that seen
      with in vitro-activated PB neutrophils. Soluble L-selectin was detected at
      similar levels in SF and PB. CONCLUSION: The phenotypic profile of SF neutrophils
      (low levels of L-selectin, CD43, and CD44, and high levels of CD11b) from most
      patients with RA or other inflammatory joint conditions resembles that observed
      in in vitro-activated neutrophils. Our results suggest that SF neutrophils are
      activated to a similar degree in inflammatory joint diseases with different
      pathogenic mechanisms.

PMID- 7510493
TI  - Digestion and fermentation of proteins in rats fed keratin, albumin, cooked
      casein and antibiotics.
AB  - Dietary cooked casein promotes colon cancer in rats. We speculated and tested the
      hypothesis that cooking reduces the digestibility of casein, and increases the
      yield of bacterial metabolites, which are potential promoters of cancer. We
      investigated dietary means to manipulate nitrogen transfer and fermentation in
      the caecum. The caecal digestion of casein (cooked or not), keratin (hydrolysed
      or not) and bovine serum albumin (oxidized or not) was measured in rats. Protein
      fermentation was estimated by assaying caecal ammonia and branched-chain fatty
      acids. Keratin and cooked casein were digested to a very low extent, and were
      poorly fermented. Rats given cooked casein had 2-3 times more ammonia in their
      caecum than animals given the other proteins. Antibiotics (bacitracin,
      chlortetracycline, neomycin and spiramycin, at either 20 and 80 micrograms/ml
      water) decreased caecal ammonia in rats eating cooked casein, with spiramycin
      being most efficient. These data support the hypothesis given above, and provide
      ways to manipulate caecal ammonia.

PMID- 7510497
TI  - Nucleic acid structure analysis: a users guide to a collection of new analysis
      programs.
AB  - Common nomenclature describing the geometry of nucleic acid structures was
      established at a 1988 EMBO Workshop on DNA Curvature and Bending (Diekmann, S.
      (1988) J. Mol. Biol. 208, 787-791; Diekmann, S. (1989) The EMBO Journal 8, 1-4;
      Sarma, R.H. (1988) J. Biomol. Structure & Dynamics 6, 391-395; Dickerson, R.E.
      (1989) J. Biomol. Structure & Dynamics 6, 627-634; Dickerson, R.E. et al. (1989)
      Nuc. Acids Res. 17, 1979-1803). We have subsequently developed and incorporated
      sophisticated mathematics in a computer program to calculate the parameters
      described by the guidelines. The program calculates all the local parameters
      relating complementary bases and neighboring base and base pairs in both
      Cartesian and helical coordinate frames. In addition, the main mathematical
      property requested by the EMBO guidelines--that the magnitude of the parameters
      be independent of strand or direction of measurement--is accomplished without the
      use of a midway coordinate frame for the rotational parameters. The mathematics
      preserve the physical intuition used in defining the parameters; in particular,
      the rotational parameters are true rotations based on a simple physical model
      (rotation at constant angular velocity for a unit amount of time), not Euler
      angles or angles between vectors and planes as is the case with other approaches.
      As a result, the mathematical equations are symmetric with the property that a 5
      degrees tilt is the same as a 5 degrees roll or a 5 degrees twist, except that
      the rotations take place about different axes. In other approaches, a 5 degrees
      tilt can mean a different amount of net rotation from a 5 degrees roll or a 5
      degrees twist. In addition, a great deal of flexibility is built into the program
      so that the user has control over the analysis, including the input format, the
      coordinate frame used for the base pairing relationship, the point about which
      the rotations are performed, and which geometric relationships are analyzed.
      While there is a great deal of flexibility, the program is easy to use.
      Interactive queries and user accessible files make the options in the program
      very convenient to tailor to individual needs. In addition, there is also a
      program that calculates bond lengths, valence angles, and torsion angles along
      the nucleic acid backbone, and within the sugar and base rings. Another program
      'learns' the identities of the bond lengths, valence angles, and torsion angles
      that the user would like to determine.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7510494
TI  - Monoclonal antibody BW494 defines a blood group Lewisa/type 1 chain-related
      antigen on carcinoma-associated mucins.
AB  - The murine monoclonal antibody (MAb) BW494 defines a carbohydrate epitope on a
      mucin-type glycoprotein which is expressed on the majority of well-differentiated
      adenocarcinomas of the pancreas. In this contribution we present evidence for the
      detailed structural requirements of the BW494 interaction with the glycan
      portions on (neo)glycoproteins or (neo)glycolipids as revealed by solid-phase
      binding assays and inhibition assays of BW494 binding to synthetic antigens or to
      the affinity-isolated cancer mucin CA494. The observed cross-reactivity of spacer
      linked Gal beta 1-3GalNAc beta (TF-beta) and Gal beta 1-3GlcNAc beta (type 1
      chain) is indicative of an epitope that comprises a terminal Gal beta 1-3HexNAc
      unit. The active conformation of this epitope is critically influenced by the
      chemical environment of the terminal disaccharide, i.e. by adjacent aglycon or
      spacer moieties or by substitution with further sugar residues at the reducing
      end. Although a strong enhancement of antibody binding is observed for the type 1
      chain derived Lea antigen, MAb BW494 is distinct in its reactivity from Lea
      specific antibodies.

PMID- 7510496
TI  - A unique or essentially unique single parametric characterisation of biopolymeric
      structures.
AB  - A generalised method of characterising the three dimensional structure of any
      biopolymer is proposed. The method makes use of rotation and superposition of
      identical rigid monomeric units that comprise the polymer. Out of the various
      parameters involved (refers the seven parametric representation of relating two
      identical rigid bodies in space), the angle of rotation and superposition termed
      as 'phi s' turns out to be essentially unique. An ideal biopolymer with n
      identical rigid units is characterised by (n-1) such unique angles. In applying
      the results to real biopolymers, the importance of recognising that monomeric
      units are no more rigid but only quasi-rigid is emphasised. However, by
      appropriate choice of 'rigid' fraction of the quasi-rigid monomers, one is led,
      as first approximation, to essentially unique characterisation of the biopolymer
      with (n-1) such unique angles. The phi s as a function of residue number acts
      essentially as a finger print of the given polymeric fold and the conformation of
      the chosen biopolymer. However, the full set of seven parameters are needed for
      model building. It is emphasised that the method is general in its application to
      any polymer and the application of the results to proteins and nucleic acids is
      illustrated.

PMID- 7510498
TI  - Effect of ageing on tissue levels of amino acids involved in the nitric oxide
      pathway in rat brain.
AB  - Nitric oxide (NO) and citrulline are produced from L-arginine by the action of NO
      synthase after activation of excitatory amino acid receptors. In addition to its
      role in neurodegeneration, there is convincing evidence that NO is also involved
      in long-term potentiation, a cellular analog of learning and memory in the
      mammalian nervous system. In the present study, concentrations of L-arginine,
      citrulline, aspartic acid and glutamic acid were determined in various brain
      regions of young and old rats. The aim was to examine whether changes in brain
      concentrations of these amino acids might be indicative of a possible decrease in
      NO production with ageing, in relation with the well-established decline of
      cognitive function. Brain aspartic acid, citrulline and L-arginine concentrations
      were found to be lower in old rats compared to young animals, although the
      decrease did not always reach statistical significance. In contrast, no change in
      glutamic acid levels was found. In all brain structures of young and old rats,
      concentrations of L-arginine were higher than the concentration for NO synthase
      to function at maximum velocity in the rat brain. Therefore, the decrease in
      citrulline concentrations found in some brain regions of old rats might be seen,
      at least partly, as a reflection of a lower production of NO with ageing,
      although further work is clearly needed to ascertain a decrease in rat brain NO
      synthase activity with age.

PMID- 7510499
TI  - Extrahypothalamic effects of melatonin administration on serotonin and
      norepinephrine synthesis in female Syrian hamsters.
AB  - The effects of daily late afternoon injections of melatonin for 10 weeks on the
      metabolism of serotonin (5-HT) and norepinephrine (NE) were examined in regional
      brain extracts of intact and ovariectomized (GX) Syrian hamsters. Accumulation of
      5-HT and NE after administration of the monoamine oxidase inhibitor pargyline was
      used as a measure of the rate of neurotransmitter synthesis-with concentrations
      determined by HPLC with electrochemical detection. Daytime 5-HT synthesis was
      significantly decreased in the amygdala of melatonin-treated hamsters that had
      been GX (to 50% of GX controls). No significant effect on 5-HT synthesis could be
      detected in the mediobasal hypothalamus (MBH), however, a significant increase
      was demonstrated in the pontine brain stem of both intact and GX hamsters treated
      with melatonin. Daytime NE synthesis was decreased to levels not significantly
      different from zero in the amygdala of GX hamsters treated with melatonin, while
      in the brain stem, melatonin reduced NE synthesis in both intact and GX animals.
      The present data demonstrate that these melatonin effects on 5-HT and NE
      metabolism are not limited to the MBH and are not secondary to melatonin-induced
      changes in circulating levels of the ovarian steroids.

PMID- 7510495
TI  - Reducing chemotherapy-induced nausea and vomiting. Current perspectives and
      future possibilities.
AB  - Nausea and vomiting are among the most distressing adverse effects of cancer
      chemotherapy. In the last 10 years considerable advances in the prevention of
      chemotherapy-induced emesis have been made. From an analysis of the results
      obtained in patients receiving moderately- to severely-emetogenic drugs the
      following guidelines in choosing the best antiemetic treatment can be given: 1.
      For the prevention of acute emesis induced by a high single dose of cisplatin (>
      or = 50 mg/m2) or by low doses (20 to 40 mg/m2) repeated for 4 to 5 days, the
      combination of ondansetron plus dexamethasone is the most efficacious and least
      toxic antiemetic therapy. 2. For the prevention of delayed emesis the combination
      of oral dexamethasone plus metoclopramide seems to offer the best protection,
      although over 40% of patients still experience delayed nausea and vomiting. 3.
      For the prevention of acute emesis induced by moderately emetogenic drugs,
      corticosteroids (dexamethasone or methylprednisolone) are efficacious and safe
      antiemetic agents. Although equally efficacious, the serotonin (5-HT)3 receptor
      antagonists, due to their higher acquisition costs, are indicated only in
      patients refractory to corticosteroids or in those who cannot use them.
      Unresolved problems in antiemetic research include: (i) identification of the
      best antiemetic treatment for those areas of cancer chemotherapy where adequate
      data are lacking, such as high dose regimens for bone marrow transplantation;
      (ii) optimisation of treatment for the most widely used chemotherapy regimens;
      and (iii) identification of the best rescue treatment for patients who fail to
      respond to antiemetic prophylaxis. Although many new 5-HT3 antagonists are
      currently being studied, the possible improvement in efficacy and tolerability
      brought about by these agents will probably only be marginal.

PMID- 7510500
TI  - Gnets, Wnets, and Rnets for antibody epitope mapping.

PMID- 7510501
TI  - 'Touching an elephant in the darkness', or 'how to get the whole picture of
      biotechnology'.

PMID- 7510503
TI  - [Pollution due to automobile traffic in the region of Presidi Cardarelli,
      Santobono e Presidio Multizonale di Prevenzione della USL 40 di Na di Napoli].
AB  - A control of air pollution has been performed in the Hospital Area of Naples
      during a period of two years, from 1988 to 1990. The concentration of inert
      suspended dust, lead and the respirable fraction of both components has been
      determined to obtain information about air pollutants produced by vehicular
      traffic which is very high in the observed zone.

PMID- 7510502
TI  - Ultrastructure of phosphotungstic acid (PTA) positive deposits in the hippocampus
      of senile demented patients.
AB  - To perform a quantitative investigation on synaptic ultrastructural features in
      the human hippocampus in normal old and senile demented patients we stained our
      tissue samples by means of the ethanol-phosphotungstic acid (E-PTA) preferential
      technique. In addition to the synaptic contact zones, we found that structures
      similar to neurofibrillary tangles (NFT) and senile plaques (SP) were remarkably
      positive to our staining procedure, while the background was faintly electron
      lucent. On the basis of the E-PTA staining properties and specificity, we support
      that the reactive sites of these positive structures are represented by basic
      amino acids. The recently demonstrated presence of 4 basic amino acids (1
      arginine, 3 histidine) in the cleaved fragment of the amyloid precursor protein
      (APP) suggest us to hypothesise that this APP portion may represent the common
      constitutive element of the many morphologically different alterations found in
      the brains of senile demented patients.

PMID- 7510504
TI  - Human osteoclast-like cells recognize laminin via an RGD independent mechanism.
AB  - Interactions between cells from human giant cell tumors of bone and the
      extracellular matrix protein laminin were studied. Cells were capable of
      recognizing this substratum via a RGD-independent mechanism. Recognition induces
      adhesion and spreading onto laminin. This protein triggered the release of
      cellular FN which in turn enhanced recruitment of the beta 1 chain-containing
      integrin receptor.

PMID- 7510505
TI  - In-vitro and in-vivo immunobiological properties of murine monoclonal anti
      Brucella antibodies.
AB  - Features and protective activity of anti-Brucella murine monoclonal antibodies
      (Mabs) versus B. melitensis 16M were studied. All Mabs tested were able to confer
      a good passive protection and showed correlative biological properties in
      immunological reactions.

PMID- 7510506
TI  - Growth of "new" coronary vascular structures by angiogenetic growth factors.
AB  - The efficacy of the human angiogenetic heparin-binding growth factor I (HBGF-I)
      to initiate site-directed growth of new blood vessels from the aorta into the
      myocardium was studied. First, manipulated Escherichia coli bacteria, which had
      received the human mRNA-transcript for HBGF I into their genetic material, were
      cultivated. The growth factor derived was purified using heparin-Sepharose
      affinity chromatography. The separation and characterization of biologically
      active alpha- and beta-chains was carried out using high pressure liquid
      chromatography (HPLC) of dialyzed and lyophilized samples from the heparin
      Sepharose column. One microgram HBGF I (alpha-ECGF) was bound to
      polytetrafluoroethylene (PTFE) sponges, precoated with collagen type I, and
      implanted between the aorta and the myocardium of the left ventricle in
      experimental rats. Twelve growth factor implants in the experimental group were
      compared to six controls receiving uncoated PTFE sponges for 9 weeks. Digitized
      computed angiography showed new blood vessels between the aorta and the
      myocardium in 11 of the 12 experimental animals, and retrograde coronary
      perfusion by these "new" vascular structures could be seen. Histology showed no
      specific structures in the control group (without HBGF I). In the experimental
      group (with HBGF I) individual vessels with highly differentiated endothelial and
      smooth muscle cell layers were evident. Our experiments proved the feasibility of
      induced, site-directed angiogenesis. It is possible to initiate in vivo growth of
      new "coronary" vascular structures between the aorta and the myocardium.

PMID- 7510507
TI  - Immunohistochemical analysis of neurons and their projections in the proximal
      colon of the guinea-pig.
AB  - The arrangement of the enteric nerve plexuses, and the distributions and
      projections of chemically specified neurons in the proximal colon of the guinea
      pig were studied. The neural plexuses were examined using immunoreactivity to
      neuron specific enolase, and individual subpopulations were studied using
      antibodies raised against vasoactive intestinal peptide (VIP), substance P (SP),
      enkephalin, neuropeptide Y (NPY), gastrin releasing peptide (GRP), galanin,
      somatostatin, calbindin and calretinin. Nitric oxide producing neurons were
      studied using NADPH diaphorase histochemistry. The myenteric and submucous
      plexuses were not uniform around the entire circumference; at the mesenteric
      aspect of the colon there was almost no longitudinal muscle and the circular
      muscle was unusually thick and cord-like. In this region there was no tertiary
      plexus of fibres, and the ganglia of the myenteric and submucous plexuses were
      elongated in the direction of the circular muscle. Neuronal pathways within the
      antimesenteric aspect of the colon were investigated using nerve lesioning
      procedures. VIP, GRP, galanin, calbindin and NADPH diaphorase containing neurons
      lay in anally projecting pathways within the myenteric plexus, while enkephalin
      and somatostatin appeared in orally projecting nerve pathways. Few NPY
      immunoreactive nerve cells were found in the myenteric plexus of the proximal
      colon. The longitudinal muscle was innervated with VIP, SP, enkephalin and NADPH
      diaphorase containing fibres. The circular muscle was innervated by axons
      containing all substances investigated except NPY. Galanin, NPY, somatostatin and
      VIP fibres, all particularly dense in the mucosa, largely arose from nerve cell
      bodies in the submucous plexus. The results of the present study indicate that
      chemically specified neuronal populations in the proximal colon of the guinea-pig
      are more similar to the distal colon than the ileum, but that neuro-chemical and
      anatomical differences exist between the proximal and distal colon.

PMID- 7510508
TI  - An immunohistochemical study of sensory and autonomic innervation of the dog
      tongue with special reference to substance P- and calcitonin gene-related peptide
      containing fibers in blood vessels and the intralingual ganglia.
AB  - The distribution, pathways and origins of peptide-containing nerve fibers in the
      anterior two thirds of the dog tongue were investigated using
      immunohistochemistry combined with retrograde axonal tracing and denervation
      experiments. Within the epithelium of the fungiform papillae, varicose nerve
      fibers immunoreactive to substance P (SP) and calcitonin gene-related peptide
      (CGRP) were present. These disappeared completely after severance of the lingual
      nerve (LN) alone. Dense CGRP-immunoreactive varicose fibers surrounded cell
      bodies in the intralingual ganglia (ILG), which consisted of neurons
      immunoreactive to vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY)
      and SP. These CGRP-immunoreactive fibers disappeared following severance of the
      chorda tympani (CT) alone. SP-, CGRP-, VIP-, NPY- and tyrosine hydroxylase (TH)
      immunoreactive nerve fibers were distributed around the walls of blood vessels,
      especially arteriovenous anastomoses (AVAs). None of these immunoreactive fibers
      completely disappeared after severance of the LN or CT alone, but SP- and CGRP
      immunoreactive fibers disappeared following severance of both the LN and CT. TH
      immunoreactive fibers disappeared after ganglionectomy of the superior cervical
      ganglion (SCG) or severance of the hypoglossal nerve (HGN). VIP- and NPY
      immunoreactive fibers invariably remained after various denervation experiments.
      In tracing experiments, CGRP-immunoreactive as well as SP and CGRP-immunoreactive
      cells in the trigeminal ganglion were labelled from the LN, and those in the
      geniculate ganglion and jugular ganglion were labelled from the CT. A large
      number of neurons in the SCG were labelled from the HGN, with some of these being
      SP and CGRP-immunoreactive. These results demonstrate that SP- and CGRP
      immunoreactive fibers from the trigeminal ganglion are distributed to the lingual
      epithelium; vascular walls receive SP- and CGRP-immunoreactive sensory fibers
      from the LN as well as CT, some SP and CGRP-immunoreactive fibers from the SCG in
      addition to catecholaminergic sympathetic fibers, and VIP- and NPY-immunoreactive
      parasympathetic fibers from the ILG. The ILG is also considered to be innervated
      by CGRP-immunoreactive sensory fibers from the CT.

PMID- 7510509
TI  - [Endoscopic prosthesis insertion in the palliative treatment of malignant
      esophageal stenosis. (Endoscopic esophageal prosthesis)].
AB  - We report our experience with endoscopic esophageal prosthesis in the treatment
      of 82 patients with advanced malignant oesophageal stenosis. The cause of the
      stenosis was an esophageal or esophagogastric cancer in 75 cases and a
      bronchogenic cancer in 7 patients. In 18 cases a tracheobronchial fistula was
      also present. A silicone tube (Atkinson) was used in 58 patients, a polyvinyl
      tube (Wilson-Cook) in 22 cases and a self-expanding tube in the remaining 2
      patients. There was no technical failure in the insertion of the prosthesis. A
      normal feeding was possible in 71 of the 82 patients (86%) within 48 after the
      intubation. Major complications occurred in 8 cases (9.7%), 4 patients with
      esophageal perforation and 4 cases with aspiration bronchopneumonia.
      Postoperative mortality rate was 7.3%, one patient with perforation, 3 cases with
      aspiration bronchopneumonia and 2 patients with sepsis. The prosthesis partially
      displaced in 9 cases, but could be endoscopically replaced in all of them. The
      displacement of the prosthesis was complete in 3 patients, one of which needed a
      surgical procedure to remove the tube. The prosthesis was bunged up by a solid
      meal bolus in 4 cases, but an endoscopic procedure was successful in removing the
      bolus. Therapy with laser was necessary in two cases with self-expanding
      prosthesis obstructed by tumoral growth. We conclude that, in malignant
      esophageal stenosis, the endoscopic implantation of esophageal endoprosthesis is
      an effective, cheap and relatively safe palliative therapeutic alternative with a
      low postoperative mortality rate.

PMID- 7510510
TI  - Effects of extradural anaesthesia on interleukin-6 and acute phase response to
      surgery.
AB  - Serum concentrations of the cytokine, interleukin-6 (IL-6), increase after
      surgical trauma. IL-6 mediates the synthesis of acute phase proteins and
      stimulates secretion of pituitary hormones. We have examined the time course of
      circulating IL-6, and cortisol and growth hormone responses in patients
      undergoing hysterectomy to determine if IL-6 contributes to the early pituitary
      hormone changes found during surgery. One group (n = 8) received a standardized
      general anaesthetic while the remaining patients (n = 8) received extradural
      analgesia to T4-S5 in addition to a similar general anaesthetic. In the general
      anaesthesia group, there was a significant increase in serum cortisol and growth
      hormone concentrations before any changes in IL-6 were detected. Furthermore, in
      the extradural group, in whom these hormonal responses were attenuated,
      circulating IL-6 concentrations did not differ significantly from the general
      anaesthesia group. There were no significant differences between the groups in
      the acute phase response, as measured by circulating concentrations of C-reactive
      protein and zinc, but the expected effects of extradural block on circulating
      metabolites and white cell count were demonstrated. We conclude that IL-6 is
      unlikely to contribute to the initial increases in secretion of pituitary
      hormones found during surgery, but a later effect of the cytokine on endocrine
      responses cannot be excluded.

PMID- 7510511
TI  - Renal tubular acidosis preceding systemic lupus erythematosus.
AB  - A 10-year-old girl with distal renal tubular acidosis (RTA) for 4 years
      (adequately treated for 3 years) developed clinical features suggesting systemic
      lupus erythematosus (SLE) with supportive laboratory evidence. She had heavy
      proteinuria and a decreased creatinine clearance (CCr). Renal biopsy showed
      diffuse proliferative and sclerosing glomerulonephritis with severe
      tubulointerstitial changes. Following treatment with corticosteroids and
      cyclophosphamide, she had a clinical remission, an increase in CCr and recovery
      from systemic acidosis. It is likely that distal RTA in this patient was a
      manifestation of SLE.

PMID- 7510513
TI  - B-cell antigen marker expression in nasopharyngeal carcinoma.
AB  - Immunohistochemical analysis was carried out to examine the characteristics of
      nasopharyngeal carcinoma (NPC) using 38 biopsy cases obtained from southern
      China. These cases were divided into 3 groups according to their predominant
      pattern associated with cell and tissue differentiation which is based on World
      Health Organization (WHO) classification as follows: 6 cases of squamous cell
      carcinoma (16%), 25 cases of differentiated non-keratinizing carcinoma (66%), 7
      cases of undifferentiated carcinoma (18%). All tumor tissues reacted with MB-1,
      but they did not react with L26 (CD20), 4KB5 (CD45R), MT-1, and leukocyte common
      antigen (LCA). Keratin and epithelial membrane antigen (EMA) as epithelial
      markers focally stained NPC tissues in all cases. Carcinoembryonic antigen (CEA)
      positive staining was detected in 7 (28%) of the 25 cases of differentiated non
      keratinizing carcinoma and in 3 (43%) of the 7 cases of undifferentiated
      carcinoma; thus, of 38 cases, 10 (26%) were CEA-positive. On the other hand,
      squamous cell carcinoma cases did not react with CEA. These NPC tissues did not
      react with S-100 protein, alpha-1-antichymotrypsin (ACT), lysozyme, vimentin, and
      desmin. Therefore, it is concluded that some cases of NPC are difficult to
      distinguish from malignant lymphoma. In certain cases, NPC may be distinguished
      from malignant lymphoma, using immunohistochemical methods for the detection of
      MB-1, keratin, EMA, and LCA. Specifically, this evidence suggests that MB-1 may
      be useful as a tumor marker of NPC. Moreover, the CEA reaction to NPC may be
      related to the cell differentiation.

PMID- 7510512
TI  - Sodium-phosphate transport in the kidney and intestine of the hypophosphatemic
      mouse.
AB  - X-linked hypophosphatemic vitamin D-resistant rickets is the most common
      inherited form of vitamin D-resistant rickets in man. The current studies were
      designed to characterize the defect in the sodium (Na+)-phosphate transporter in
      the (Hyp) mouse model. The slope of initial rate of phosphate uptake was
      significantly decreased in the kidney but not in intestinal brush border
      membranes of the (Hyp) mice compared with genetically matched controls. Phosphate
      uptake by the basolateral membranes of the intestine and kidney was similar in
      the (Hyp) and control mice. Kinetic analysis of phosphate uptake by renal brush
      border membranes showed a Vmax of 0.32 +/- 0.06 and 1.6 +/- 0.1 nmol/mg protein
      per 15 s (P < 0.01) and Km of 0.07 +/- 0.06 and 0.39 +/- 0.05 mM in (Hyp) and
      control mice respectively (P < 0.05). Vmax and Kmax of jejunal uptake of
      phosphate were similar in (Hyp) and control mice. To confirm these findings, we
      expressed the Na(+)-phosphate transporter in Xenopus laevis oocytes. Na(+)
      dependent phosphate uptake in the oocytes was expressed 6 days after renal and
      intestinal poly(A)+ RNA injection, however, uptake values were significantly
      lower in oocytes injected with renal poly(A)+ RNA from the (Hyp) mice compared
      with controls (P < 0.01). No differences were noted in phosphate uptake by
      oocytes injected with poly(A)+ RNA from the jejunum of the (Hyp) or control mice.
      These studies suggest that the defect in the (Hyp) mice is localized to the
      kidney and is secondary to diminished activity and/or function of the Na(+)
      phosphate transporter.

PMID- 7510514
TI  - [Primary squamous cell carcinomas of the endometrium. Clinico-pathologic data and
      histogenetic classification].
AB  - Primary squamous cell carcinomas of the endometrium are rare tumours. We have
      studied 7 primary and 2 secondary squamous cell carcinomas immunohistochemically
      with anti-all-cytokeratin (KL 1), anti-CEA and anti-vimentin. The non
      keratinizing carcinomas and the non-keratinizing component of the keratinizing
      carcinomas showed a strong expression of vimentin. Contrary to this, the
      keratinizing parts were strongly positive with anti-CEA. Additionally, some cases
      showed a direct transformation of the (dysplastic) glandular endometrial
      epithelium into neoplastic squamous cells. These findings suggest that the
      primary squamous cell carcinoma of the endometrium is the result of a
      bidirectional differentiation of pluripotent endometrial precursor cells. Like in
      other non-endometrioid adenocarcinomas, such metaplasias develop from pluripotent
      Mullerian epithelium. They show various differentiations, perhaps endocervical
      determination with keratinization and positive reaction against CEA or primitive
      endometrioid with squamous cell appearance, positive anti-vimentin reaction and
      non-keratinization.

PMID- 7510515
TI  - Littoral cell angioma of the spleen. A case report with ultrastructural and
      immunohistochemical observations.
AB  - We describe histological, immunohistochemical and ultrastructural findings in a
      case of littoral cell angioma of the spleen in a 44 year old man. Beside
      phagocytosis and heavy haemosiderin deposits in the cytoplasm, a very
      characteristic and hitherto undescribed feature of the littoral cells was focal
      accumulations of eosinophilic globules 0.5-2 microns in size, which often
      entirely filled the cytoplasm of the tumour cells. Ultrastructurally the globules
      were composed of abundant cytoplasmic deposits of lysosomes and residual bodies.
      The globules most probably originate from the phagocytized red blood cells,
      lymphocytes and plasma cells. Immunohistochemically the tumour cells reacted
      positively with antibodies against factor VIII-related antigen, KiM1P, KP1 and
      lysozyme and negatively with antibodies against cytokeratins AE1-AE3, EMA and S
      100 protein. Ultrastructurally the tumour cells often formed long cytoplasmic
      processes without external lamina and pinocytic vesicles. Scarce and poorly
      formed junctions between the tumour cells were seen. Very rarely cytoplasmic rod
      shaped microtubulated bodies, often difficult to distinguish from heavy
      accumulations of lysosomes were observed.

PMID- 7510516
TI  - Capsaicin-induced membrane currents in cultured sensory neurons of the rat.
AB  - Membrane currents induced by capsaicin (CAPS) in cultured sensory neurons from 1-
      to 2-day-old rats were studied. Responses to CAPS (10 microM) exceeding 1 nA at 
      50 mV were found in smaller, usually bipolar or tripolar neurons in which GABA
      (30 microM) induced small or no response. Large, unipolar neurons, which
      exhibited large responses to GABA, were completely insensitive to CAPS (10
      microM). In contrast to GABA, responses to CAPS exhibited a slow rise and slow
      decay and a marked tachyphylaxis after repeated CAPS applications at high
      concentrations which made it difficult to study the concentration-response
      relationship. In partially run-down neurons, which exhibited quasi stable
      responses, the slope of the ascending phase was concentration-dependent with an
      apparent association rate constant K1 9 x 10(4) [M-1s-1]. The time constant of
      the decay was 3.5 s, and was concentration-independent. However, in 5 neurones
      the EC50 measured from the first series of CAPS applications at increasing
      concentrations was 0.31 +/- 0.5 microM with a Hill coefficient 1.66 +/- 0.35. The
      responses to CAPS reversed at +10.4 +/- 2.5 mV suggesting that the current is
      carried nonselectively by monovalent cations and Ca2+. The channel conductance of
      CAPS-gated channels at -50 mV calculated from the mean membrane current and
      variance of the current noise in outside-out patches or measured directly was 28
      pS (n = 5). It is suggested that the CAPS-gated channels are either controlled by
      receptors with a very high affinity or that the channels are controlled by
      membrane-bound protein(s) which do not depend in their function on the supply of
      GTP or other intracellular metabolites.

PMID- 7510518
TI  - Helix-loop-helix motif in HIV-1 Rev.
AB  - Circular dichroism (CD) spectra of C-terminal deletion mutants of the HIV-1 Rev
      protein, Rev M9 delta 14 (missing aa 68-112) and Rev M11 delta 14 (lacking aa 92
      112), indicated that Rev contains 46-49 residues in alpha-helical conformation
      within the N-terminal 71 or 95 amino acids of the 116 residue protein.
      Complexation with a 40-nucleotide fragment of the Rev responsive element, RRE,
      (G39 to C78), containing the minimal element for Rev binding, induced an A to B
      form structural transition in the RRE fragment, whereas the percentage of alpha
      helical conformation in the protein stays constant on substrate binding. When
      complexed to the RNA, neither mutant protein showed structural changes upon
      raising the temperature to 40 degrees C, as determined by the lack of decrease of
      the signal intensity at 222 nm, indicative for alpha-helical conformation. In
      contrast, Rev M9 delta 14, which is shorter than Rev M11 delta 14 by 24 amino
      acids, in the absence of RNA, lost about 60% of the spectral minima at 222 nm at
      the same temperature. The Rev M11 delta 14 mutant, in the absence of RNA, showed
      a decrease of 20% in spectral intensity upon heating to 40 degrees C. Free and
      RNA-bound mutant proteins showed reversible transitions upon heating to 80
      degrees C and subsequent cooling down to 10 degrees C overnight. The Rev peptide
      Cys 75-93, spanning the Rev transactivation domain, showed secondary structure in
      40% and 60% hexafluoropropanol (HFP) solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510517
TI  - Lipocortin 2 (annexin 2) is a major substrate for constitutive tyrosine kinase
      activity in chondrocytes.
AB  - Treatment of cultured bovine articular chondrocytes with 100 microM
      orthovanadate, in the absence of serum, results in the production of a single
      major tyrosine phosphorylated protein with an apparent molecular mass of 36 kDa
      (p36). Chondrocytes were found to contain proteins reactive with anti-lipocortin
      1, 2, and 5 antibodies. p36 comigrated on SDS-polyacrylamide gels with lipocortin
      2, but not with other members of the lipocortin family. The distribution of p36
      between the particulate and soluble cell fractions was also similar to that of
      lipocortin 2. p36 that was purified on an anti-phosphotyrosine immunoaffinity
      column cross-reacted with anti-lipocortin 2 antibodies. Similarly, lipocortin 2
      purified on an anti-lipocortin 2 immunoaffinity column reacted with anti
      phosphotyrosine antibodies. Furthermore, cyanogen bromide cleavage fragments of
      purified lipocortin 2 and p36 were similar. These data demonstrate that the major
      constitutively tyrosine phosphorylated protein, in chondrocytes, is lipocortin 2.
      Tyrosine phosphorylated p36 required SDS buffers for extraction due to a loss of
      the tyrosine phosphate group under other solubilization conditions using Triton X
      100 or sodium cholate. This study provides a system for the study of the effects
      of tyrosine phosphorylation on lipocortin 2 function. What role lipocortin 2
      plays in chondrocyte biology remains to be determined.

PMID- 7510519
TI  - Interaction of substance P with the second and seventh transmembrane domains of
      the neurokinin-1 receptor.
AB  - The neurokinin-1 receptor is a member of the G-protein-coupled receptor family
      and has the highest affinity for the endogenous peptide transmitter substance P.
      Previous studies have indicated that several residues in the first and second
      extracellular segments, and at least part of the transmembrane domain, of the
      human neurokinin-1 receptor are involved in substance P binding to the receptor.
      To further map the peptide binding site, single-residue substitutions in the
      transmembrane domains were analyzed. Asn-85, Asn-89, Tyr-92, and Asn-96 in the
      second transmembrane domain and Tyr-287 in the seventh transmembrane domain are
      required for the high-affinity binding of peptides, with Asn-85 possibly
      interacting with the C-terminus of substance P. In addition, Glu-78 in the second
      transmembrane domain and Tyr-205 in the fifth transmembrane domain appear to be
      involved in the receptor activation process. Some of the key residues for peptide
      binding are likely to be near those residues that are required for the binding of
      competitive antagonists (such as His-197, His-265, and Tyr-287). These data
      suggest that a volume exclusion effect can explain the competitive antagonism of
      substance P binding by non-peptide antagonists. Furthermore, the key residues
      identified thus far are required for the high-affinity binding of all three
      neurokinin peptides, consistent with a hypothesis that the conformational
      compatibility between the receptor and the peptide agonist may be a major
      determinant of peptide recognition.

PMID- 7510521
TI  - Effects of herbimycin A and ST638 on Fc epsilon receptor-mediated histamine
      release and Ca2+ signals in rat basophilic leukemia (RBL-2H3) cells.
AB  - We examined the effect of the two protein tyrosine kinase inhibitors, alpha-cyano
      3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamide (ST638) and herbimycin A, on the
      activation processes of rat basophilic leukemia (RBL-2H3) cells by cross-linking
      of IgE receptors. RBL-2H3 cells sensitized with DNP-specific monoclonal IgE
      antibody were stimulated with multivalent antigen (DNP conjugate of bovine serum
      albumin). Analysis of phosphotyrosine-containing proteins in their lysates by SDS
      PAGE and immunoblotting revealed that these two inhibitors efficiently inhibited
      the tyrosine phosphorylation of several proteins (32, 42, 56, 66, 72, 92, 150
      kDa) including phospholipase C-gamma 1. The inhibitors also caused parallel
      inhibitions of the histamine release, the formation of inositol 1,4,5
      trisphosphate, and the increase in cytosolic calcium ion concentration at the
      late sustained phase. A digital imaging fluorescence microscopic analysis of
      antigen-dependent calcium signals in individual cells showed that these two
      tyrosine kinase inhibitors inhibited the calcium influx from the external medium
      more powerfully than the mobilization of calcium ion from internal stores. In
      contrast, the inhibitors did not affect the increase in the cytosolic calcium ion
      concentration or the histamine release induced by the calcium ionophore A23187.
      Taken together, our results suggest that tyrosine phosphorylation following
      antigen stimulation regulates phosphatidylinositol hydrolysis and the influx of
      extracellular calcium.

PMID- 7510522
TI  - Thioallyl compounds: potent inhibitors of cell proliferation.
AB  - S-Allylmercaptocysteine was shown to inhibit vascular smooth-muscle and umbilical
      endothelial cell proliferation. Inhibition was dose-dependent and affected smooth
      muscle cells more than endothelial cells. S-Allylmercaptocysteine was two orders
      of magnitude more potent than S-allylcysteine and cells grown in its presence
      showed distinct changes in their phosphorylation compared to untreated controls.
      Among the proteins whose phosphorylation was altered were GTP-activating protein,
      protein tyrosine phosphatase-1B and p34cdc2. We conclude that thioallyl
      compounds, natural constituents of garlic and known to inhibit malignant cells,
      can also reduce the proliferation of normal cells.

PMID- 7510523
TI  - Involvement of protein kinase A and C in the production of interleukin-1 alpha
      induced prostaglandin E2 from mouse osteoblast-like cell line, MC3T3-E1.
AB  - Human recombinant interleukin-1 alpha (IL-1) stimulated the mouse osteoblast-like
      cell line, MC3T3-E1, to produce prostaglandin E2 (PGE2). This was inhibited by 1
      (5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) in a dose-dependent manner. The
      protein kinase A (PKA)-specific inhibitor, KT5720, also inhibited the IL-1
      induced PGE2 production in MC3T3-E1 cells, as did staurosporine, a potent
      inhibitor of protein kinase C (PKC). The PKA activator, 8-bromoadenosine 3',5'
      cyclic monophosphate (8-Br-cAMP), weakly stimulated MC3T3-E1 cells to produce
      PGE2, as did the PKC activator, 12-O-tetradecanoylphorbol 13-acetate (TPA).
      However, 8-Br-cAMP and TPA acted synergistically to induce PGE2 production equal
      to that of IL-1. These observations suggest that activation of both PKA and PKC
      are involved in IL-1-induced PGE2 production in MC3T3-E1 cells.

PMID- 7510524
TI  - Inoperable thyroid carcinoma: palliation with percutaneous injection of ethanol.

PMID- 7510520
TI  - Supporting Youth in a Time of Social Change. An Invitational Conference on
      Adolescent Health and Development: A Focus on the Americas. March 1992.

PMID- 7510526
TI  - Power spectra and cooperativity of a calcium-regulated cation channel.
AB  - In this article we show that a channel complex of cooperatively interacting
      subunits can produce a power law spectrum with the slope of the spectrum
      depending on the strength of the cooperative interaction. The effects of
      cooperativity are explored via a computational model of a calcium-regulated
      cation channel for which new data is presented. The results, which concern
      "flickering" conductances, are correlated with prior work on critical
      fluctuations in the Ising model of ferromagnetism.

PMID- 7510527
TI  - Correction for missed events based on a realistic model of a detector.
AB  - Quantitative patch-clamp analysis based on dwell-time histograms has to deal with
      the problem of missed events. The correction of the evaluated time constants has
      to take into account the characteristics of the detector used for the
      reconstruction of the time series. In previous approaches a simple model of the
      detector has been used, which is based on the assumption that all events shorter
      than the temporal resolution tres were missed, irrespective of the preceding
      events. Rather than the standard assumption of a fixed dead time, we introduce a
      more realistic model of a detector by a continuous-time version of the Hinkley
      detector. The combined state of the channel and the detector obeys a Markov
      model, which is governed by a Fokker-Planck-Kolmogorov partial differential
      equation. The steady-state solution leads to the determination of the apparent
      time constants tau o and tau c depending on the true rate constants koc and kco
      and the temporal resolution tres of the detector. Simulations with different
      kinds of detectors, including the Bessel filter with half-amplitude threshold
      detection, are performed. They show that our new equation predicts the dependence
      of tau c and tau o on koc, kco, and tres better than the standard equation used
      until now.

PMID- 7510525
TI  - Orientations of the tryptophan 9 and 11 side chains of the gramicidin channel
      based on deuterium nuclear magnetic resonance spectroscopy.
AB  - Deuterium nuclear magnetic resonance spectroscopy was used to investigate the
      orientations of the indole rings of Trp9 and Trp11 in specific indole-d5-labeled
      samples of gramicidin A incorporated into dimyristoyl phosphatidylcholine
      bilayers in the beta 6.3 channel conformation. The magnitudes and signs of the
      deuterium quadrupolar splittings were fit to the rings and assigned to specific
      ring bonds, using a full rotation search of the chi 1 and chi 2 angles of each
      Trp and a least-squares method. Unique assignments were obtained. The data and
      assignments are in close agreement with four sets of (chi 1, chi 2) angles for
      each Trp in which the indole N-H is oriented toward the membrane's exterior
      surface. (Four additional sets of (chi 1, chi 2) angles with the N-H's pointing
      toward the membrane interior are inconsistent with previous observations.) One of
      the sets of (chi 1, chi 2) angles for each Trp is consistent with the
      corresponding Trp orientation found by Arsen'ev et al. (1986. Biol. Membr. 3:1077
      1104) for gramicidin in sodium dodecyl sulfate micelles. Together, the 1H and 2H
      nuclear magnetic resonance methods suggest that the Trp9 and Trp11 side chain
      orientations could be very similar in dimyristoyl phosphatidylcholine membranes
      and in sodium dodecyl sulfate micelles. The data for Trp11 could be fit using a
      static quadrupolar coupling constant of 180 kHz under the assumption that the
      ring is essentially immobile. By contrast, Trp9 could be fit only under the
      assumption that the quadrupolar splittings for ring 9 are reduced by
      approximately 14% due to motional averaging. Such a difference in motional
      averaging between rings 11 and 9 is also consistent with the 15N data of Hu et
      al. (1993. Biochemistry. 32:7035-7047).

PMID- 7510528
TI  - Long-range interactions, voltage sensitivity, and ion conduction in S4 segments
      of excitable channels.
AB  - Forces acting on the S4 segments of the channel, the voltage-sensing structures,
      are analyzed. The conformational change in the Na channel is modeled as a helix
      coil transition in the four S4 segments, coupled to the membrane voltage by
      electrical forces. In the model, repulsions between like charges make the S4
      segment unstable, but field-dependent forces hold it in an alpha-helix
      configuration at resting potential. At threshold depolarization, the S4 helices
      cooperatively expand into random coils, breaking the hydrogen bonds connecting
      adjacent loops of the alpha helices. Exposed electron pairs left on the carbonyl
      oxygens constitute sites at which cations can bind selectively. The first
      hydrogen bond to break is at the channel exterior, then the second breaks, and so
      on in a zipper-like motion along the entire segment. The Na+ ions hop from one
      site to the next until all H bonds are broken and all sites are filled with ions.
      This completes the pathway over which the permeant ions move through the channel,
      driven by the electrochemical potential difference across the membrane. This
      microscopic mechanism is consistent with the thermodynamic explanation of ion
      channel gating previously formulated as the ferroelectric-superionic transition
      hypothesis.

PMID- 7510531
TI  - Transduction of membrane tension by the ion channel alamethicin.
AB  - Mechanoelectrical transduction in biological cells is generally attributed to
      tension-sensitive ion channels, but their mechanisms and physiology remain
      controversial due to the elusiveness of the channel proteins and potential
      cytoskeletal interactions. Our discovery of membrane tension sensitivity in ion
      channels formed by the protein alamethicin reconstituted into pure lipid
      membranes has demonstrated two simple physical mechanisms of cytoskeleton
      independent transduction. Single channel analysis has shown that membrane tension
      energizes mechanical work for changes of conductance state equal to tension times
      the associated increase in membrane area. Results show a approximately 40 A2
      increase in pore area and transfer of an 80-A2 polypeptide into the membrane.
      Both mechanisms may be implicated in mechanical signal transduction by cells.

PMID- 7510530
TI  - A simple model for surface charge on ion channel proteins.
AB  - We present a simple two-parameter model for surface charge directly associated
      with ion channels. A spherically symmetric "charged shell" models a distribution
      of surface charge arrayed about the channel entrance, with a corresponding set of
      image charges behind the plane of the membrane. The transition between a regime
      of buffered conductance and a regime of rapidly falling conductance at very low
      ionic strength is found to depend on the magnitude of the surface charge as well
      as the separation between the charge and the channel entrance. This resolves an
      apparent discrepancy between the experimental findings of Naranjo and Latorre
      (1993. Biophys. J. 64:1038-1050) and previous theoretical computations. The
      charged-shell model is used in a comparative study of the toad skeletal muscle
      conductance data of Naranjo and Latorre, the rat skeletal muscle conductances of
      Ravindran et al. (1992. Biophys. J. 61:494-508), and a second set of rat muscle
      conductances presented in this paper.

PMID- 7510532
TI  - Closed state of gramicidin channel detected by X-ray in-plane scattering.
AB  - An analogue of gramicidin A (gA) was synthesized with the formyl group replaced
      by a BOC group. The analogue (BOC-gA) exhibited single channel conduction, but
      the channel is 5-order-of-magnitude destabilized relative to the gA channel.
      Hydrated mixtures of gramicidin and dilauroyl phosphatidylcholine in the molar
      ratio of 1:10 were prepared into uniformly aligned multiple bilayers, and X-ray
      scattering with the momentum transfer in the plane of the membrane was measured.
      Analysis with the help of computer simulations showed that 70% of BOC-gA are
      monomers. Thus for the first time it was shown that gramicidin monomers are
      stable inside the monolayers of a lipid membrane. Furthermore, the monomers have
      the same beta helical conformation as the dimeric channel. The result suggests
      the possibility that when a gramicidin channel is closed, it dissociates into two
      monomers floating in opposite monolayers.

PMID- 7510529
TI  - FMRFamide and membrane stretch as activators of the Aplysia S-channel.
AB  - The long-standing distinction between channels and transporters is becoming
      blurred, with one pump protein even able to convert reversibly to a channel in
      response to osmotic shock. In this light, it is plausible that stretch channels,
      membrane proteins whose physiological roles have been elusive, may be
      transporters exhibiting channel-like properties in response to mechanical stress.
      We recently described a case, however, where this seems an unlikely explanation.
      An Aplysia K channel whose physiological pedigree is well established (it is an
      excitability-modulating conductance mechanism) was found able to be activated by
      stretch. Here we establish more firmly the identity of this Aplysia conductance,
      the S-channel, as a stretch channel. We show that the permeation and fast kinetic
      properties of the stretch-activated channel and of the FMRFamide-activated S
      channel are indistinguishable. We have also made progress in extending the
      kinetic analysis of the stretch channel to situations of multiple channel
      activity. This analysis implements a novel renewal theory approach and is
      therefore explained in some detail.

PMID- 7510533
TI  - Membranoproliferative glomerulonephritis associated with hepatitis C virus
      infection.
AB  - The hepatitis C virus genome has been recently sequenced and cloned, allowing the
      identification of patients exposed to this virus, which is now felt to be the
      principal cause of "non-A, non-B" hepatitis. The hepatitis B virus has long been
      implicated in the pathogenesis of several glomerulopathies including
      membranoproliferative glomerulonephritis, mixed cryoglobulinemia, and membranous
      glomerulonephritis. Several authors have recently reported an association between
      hepatitis C virus infection and glomerular disease. The case of a patient with
      chronic hepatitis C virus infection who developed the nephrotic syndrome 3 months
      after liver transplantation is described. Serologic testing was significant for
      an elevated rheumatoid factor, circulating cryoglobulins, and a mildly depressed
      C4 level. Hepatitis C virus antibody and viral RNA (by polymerase chain reaction)
      were present in both the serum and cryoglobulin fraction. A renal biopsy
      demonstrated membranoproliferative glomerulonephritis. It is believed that
      persistent infection with the hepatitis C virus is responsible for an immune
      complex-mediated glomerulonephritis in this patient. Because hepatitis C has now
      been pathogenetically linked to several glomerulopathies, testing for this virus
      should be considered in the serologic work-up of the patient with
      glomerulonephritis.

PMID- 7510536
TI  - DNA strandness changes during in situ hybridization conditions.
AB  - DNA strandness changes occurring during in situ hybridization were monitored
      using monoclonal antibodies. Our results show that: 1) RNase induces formation of
      single stranded DNA, 2) after denaturation-renaturation, single stranded DNA is
      found principally in centromeric areas, and 3) double stranded DNA is still
      observed after each step.

PMID- 7510534
TI  - Localization and possible role of molecules associated with the cholinergic
      system during "non-nervous" developmental events.
AB  - Data on the non-nervous location of cholinergic molecules are reviewed to give a
      general indication of their possible functions. Cholinergic or immunologically
      related molecules were detected and localized mainly in three classes of
      differentiative events supported by intracellular ion concentration changes. I:
      during gamete maturation, activation and interaction; II: during the early
      development of invertebrate and vertebrate embryos. In this case cholinergic
      molecules are located mainly in moving cells and tissues engaged in relevant
      morphogenetic events, such as gastrulation and limb bud differentiation, and are
      often codistributed with special extracellular matrix molecules (fibronectin);
      III: during inductive communications between mesenchyme and other tissues. The
      cholinergic system thus seems to be a multifunctional cell communication system.
      It appeared early during evolution as a regulator of intercellular communications
      mediated by ion dynamics, before becoming involved in highly specialized
      communication structures, such as synapses and nerve endings.

PMID- 7510535
TI  - Temporal relationships of statin and terminin expression in ventral lobe of rat
      prostate following castration.
AB  - The purpose of this study was to determine the temporal relationships, in the rat
      prostate following castration, the expressions of terminin, a cytoplasmic marker
      for senescence, and, statin, a nuclear marker for cell quiescence and senescence.
      The presence of these two proteins was determined at 0, 1, 2, 4, 8, 24 and 48
      hours in the ventral lobe of the prostate following castration.
      Immunofluorescence techniques for double labelling were used and assessed with
      confocal microscopy. At 0 hour the mean % labelling index (LI) for terminin was
      0% and 98% for statin. One hour following castration a complete reversal of
      expression of these two markers occurred indicating that the terminin marker is
      expressed at the start of programmed cell death or apoptosis. The mean % LI for
      terminin at 1, 2, 4, 8, 24 and 48 hours following castration were 54, 82, 63, 39,
      44 and 41% respectively. The mean % labelling index of statin remained at zero
      during these time intervals. It is concluded that following castration, the
      prostatic ventral lobe exits from the quiescent phase to reenter cell cycle
      traverse. This is coupled by the loss of statin and the expression of the
      cytoplasmic marker terminin at the start of programmed cell death prior to the
      appearance of any histologic features of apoptosis.

PMID- 7510537
TI  - Differential immunohistochemical staining of cancerous cells with anti-single
      stranded DNA antiserum in ordinary pathological paraffin section after DNA
      denaturation by acid hydrolysis.
AB  - Based on the finding that the nuclear DNA of cancerous cells is much more
      unstable than that of non-cancerous cells, yielding a larger amount of single
      stranded DNA by acid hydrolysis, we developed a new method of cancer cell
      detection in ordinary pathological sections by immunohistochemical staining with
      anti-single-stranded DNA antiserum after acid hydrolysis. Methylated bovine serum
      albumin was conjugated with heat-denatured calf thymus DNA and used as the
      antigen of single-stranded DNA, and white male rabbits were immunized with the
      antigen to obtain the polyclonal antiserum. Ordinary paraffin-embedded sections
      were prepared from the formalin-fixed biopsy specimens taken from 482 malignant
      tumors and 73 benign tumors of human epithelial and non-epithelial origins.
      Additional 82 biopsy specimens of borderline malignancy were also examined. The
      sections were immunohistochemically stained with the antiserum after RNase
      digestion and DNA denaturation by hydrolysis with 2 N HCl at 30 degrees C. The
      acid hydrolysis for 20-30 min was optimum for the specimens fixed with 10%
      buffered formalin at room temperature for 16-24 hrs, and all cancerous cells were
      specifically stained positive, in sharp contrast to the negative stainability of
      all non-cancerous cells including inflammatory cells. This new method gives us
      decisive help in making diagnosis of malignancy in daily pathological
      examination. The possibility of malignancy of borderline lesion was discussed.

PMID- 7510538
TI  - Fluorescent staining of nucleolar organizer regions for three-dimensional display
      by confocal laser scanning microscope.
AB  - A new method of fluorescent staining of nucleolar organizer regions (F1NORs) is
      described. Aluminum ammonium sulfate was used instead of silver as the cationic
      metal ion for binding with NORs-associated proteins, and fluorescent morin was
      successively bound to aluminum by chelating with modification of the method
      developed by Malinin (1978). After bleaching the fluorescent staining of NORs by
      washing water, ordinary AgNORs staining was performed on the same section, and
      both images of F1NORs and AgNORs were found to coincide with each other. F1NORs
      staining of human malignant and benign tumors, and colorectal adenomas of
      borderline malignancy were examined by three-dimensional analysis of the
      fluorescence images under confocal laser scanning microscope (CLSM). A remarkable
      increase of F1NORs was found, not only in number but also in volume, with bizarre
      configuration in the process of tumor progression, and the F1NORs-CLSM technique
      may be helpful for daily pathological diagnosis of malignancy.

PMID- 7510539
TI  - Peanut lectin binding sites in human foetal and neonatal pancreas.
AB  - The histochemical binding sites of peanut agglutinin (PNA) to normal foetal and
      neonatal pancreas and to pancreatic tissue from two cases with persistent
      neonatal hyperinsulinaemic hypoglycaemia were studied. For the demonstration of
      masked PNA binding sites, neuraminidase digestion was utilized. In addition,
      pancreatic endocrine cells were identified by immunocytochemistry for insulin,
      glucagon and somatostatin. Likewise, double immunohistochemical staining for
      simultaneous visualization of PNA binding sites and insulin reactive cells was
      employed. In pancreatic exocrine tissue, PNA binding occurred in all cases
      without neuraminidase treatment. Insular endocrine cells expressed PNA binding
      both in normal neonatal cases and in those with hyperinsulinaemic hypoglycaemia,
      but only after neuraminidase treatment. In foetal pancreas, no PNA binding was
      found on endocrine cells even after neuraminidase treatment, and it was also
      absent from B-cells in areas of the normal neonatal pancreas that showed the
      characteristic picture of nesidioblastosis. The possible mechanisms involved in
      determining the different pattern of PNA reactivity in foetal and neonatal
      endocrine pancreas are considered.

PMID- 7510540
TI  - Can peanut agglutinin distinguish between pseudo and true invasion in colonic
      adenomas?
AB  - We verified the binding of peanut agglutinin (PNA) in 28 pedunculated adenomas
      (10 with pseudo and 18 with true invasion, respectively) of the large bowel. The
      distribution of glycoproteins was assessed in the normal mucosa of the stalk, in
      the surface dysplastic mucosa and in the mucosa of the pseudo-invasion or
      cancerization areas. The aims of the study were to verify: the PNA role in the
      differential diagnosis between pseudo and true invasion; the changes in PNA
      binding during transformation of mucosa from the normal to dysplastic and
      neoplastic status; the PNA ability as a predictive marker in the neoplastic
      transformation. The total percentage of PNA positivity in our samples was not
      significatively higher in carcinomatous than in pseudoinvasive areas (83.3% vs
      50%). But the analysis of semiquantitative expression of PNA binding showed that
      an analogous, or reduced expression of marker in the epithelium in the submucosa
      compared to the dysplastic surface was consistent with the diagnosis of
      pseudoinvasion, while its increase strengthened the diagnosis of true invasion.
      In addition, we found a progressive increase of expression of PNA from the normal
      to dysplastic and neoplastic mucosa; therefore our data confirmed the
      quantitative relationship of this marker with malignant transformation. Finally,
      when we compared the expression of the PNA binding in solely superficial
      adenomatous tissue of benign and malignant polyps, we found an equal percentage
      of positive cases (66.6% in the carcinomatous vs 70% in the benign adenomas).
      Therefore, PNA does not recognize the risk of actual malignant evolution in an
      adenoma but is indicative of carcinomatous transformation when it is strongly
      positive.

PMID- 7510541
TI  - Light microscopic histochemical detection of sugar residues of glycoconjugates in
      human nasal mucosa using HRP-lectins.
AB  - A battery of horseradish peroxidase-conjugated lectins (ConA, WGA, PNA, SBA, DBA,
      UEAI and LTA) was used to study the content and distribution of glycoconjugate
      sugar residues of the normal human nasal mucosa. Our findings indicate that
      differences exist between the types of sugar residues found in the secretory
      product of the mucous goblet-like cells and those found in the mucous glands
      secretion. The saccharide content of the epithelial basal cells, which has never
      been previously investigated, is reported. Differences in the content and
      distribution of glycoconjugate sugar residues were found between human nasal
      mucosa and that of the other human extrapulmonary tracts.

PMID- 7510542
TI  - Vimentin- and GFAP-immunoreactivity in developing and mature neural microvessels.
      Study in the chicken tectum and cerebellum.
AB  - The expression of the cytoskeletal filaments vimentin and GFAP has been analyzed
      by immunocytochemical techniques in endothelial cells, pericytes, and astrocyte
      perivascular endfeet of microvessels of chicken optic tectum and cerebellum
      during embryonic development and in adulthood. Endothelial cells and pericytes
      were characterized by strong vimentin-immunoreactivity in both tectum and
      cerebellum only in early developmental stages (11-15 incubation days, i.d.).
      Astrocyte processes closely associated with the vessel wall were vimentin stained
      in the 11 i.d. cerebellum and vimentin-and GFAP-reactive in 15 i.d. tectum. These
      perivascular endfeet became GFAP-immuno-stained in the tectum and cerebellum by
      the 21st i.d. The results indicate that intermediate filament expression in the
      cells of the brain microvasculature is developmentally regulated, and suggest
      that the vimentin to GFAP transition in perivascular astrocytes parallels the
      vessel wall maturation.

PMID- 7510543
TI  - Collagen-glutaraldehyde interaction as revealed by the D-banding of negatively
      stained fibrils and computer-drawn band patterns.
AB  - Band patterns exhibited under electron microscope by native collagen fibrils
      fixed with glutaraldehyde (2.5%-5% GA diluted in 0.1M phosphate buffer, pH 7.4)
      and negatively stained with phosphotungstic acid (1% PTA diluted in the same
      buffer) were digitized to form both bandings and microdensitometric traces.
      Collaterally, computer-drawn band patterns and traces were yielded on the basis
      of the "quarter stagger" model and primary structure of alpha 1(I) and alpha 2(I)
      tropocollagen chains and by selecting options related to specific collagen-GA
      interactions. Comparisons between actual and simulated patterns suggest that
      lysines and hydroxylysines should react with GA residues in a 1:3 ratio, while GA
      reactivity of histidyl and tyrosyl residues seem to be excluded. On the other
      hand, an improvement of simulations was achieved by also selecting
      hydroxyprolines (in addition to lysines and hydroxylysines), which seemed to
      react with GA in a 1:1 ratio. Considering the bifunctionality of GA, it is
      suggested that during fixation, heteropolymers form, composed of GA-hexamers
      bonded to couples of lysyl and/or hydroxylysyl residues. The hypothesis is
      advanced of an additional formation of GA-dimers, each bonded to two
      hydroxyprolines.

PMID- 7510545
TI  - A single-step staining procedure for the detection and sorting of unfixed
      apoptotic thymocytes.
AB  - In this study we describe a cytometric method to sort apoptotic cell fractions,
      suitable for biochemical and morphological analyses. Rat thymocytes were used as
      a model system, as apoptosis naturally occurs in the thymus, where the negative
      selection of the T cell repertoire takes place. Massive apoptosis was induced in
      vitro by the topoisomerase-II inhibitor, etoposide. After etoposide treatment, a
      large fraction of thymocytes showed the morphological and electrophoretic
      features of apoptotic cells. Unfixed thymocytes were stained for 30 min with
      propidium iodide (PI: 50 micrograms/ml containing RNase type A and detergent),
      and analyzed by flow cytometry. Apoptotic thymocytes typically showed sub-G1 DNA
      contents. Compared to non-apoptotic thymocytes, sub-G1 cells had lower values of
      low-angle (FSC) scatter and higher values of right-angle (SSC) scatter, so that,
      in dual parameter cytograms of FSC versus SSC, two distinct cell populations were
      apparent, and were separated by flow sorting. The purified cell fractions
      obtained by this procedure had a very well preserved ultrastructural morphology;
      both early and late apoptotic stages (until the onset of cytoplasm segmentation)
      were present in the sorted apoptotic fraction.

PMID- 7510544
TI  - Rapid selection of donor myoblast clones for muscular dystrophy therapy using
      cell surface expression of NCAM.
AB  - This study describes an easy 3 step-procedure to prepare rapidly and at low cost,
      pure myoblast cell cultures from a normal muscle biopsy. Following collagenase
      and trypsin treatment of the tissue (step 1), dissociated cells were cloned at a
      density of 10 cells/ml in MCDB 120 medium (0.2 ml/well). Clones that grew were
      then tested for NCAM cell surface expression by cytofluorometric analysis (CFA)
      using Coulter CD56-PE monoclonal antibodies (step 2). Only those clones with more
      than 98% strongly labelled positive cells were expanded (step 3) for further
      trials in cell transfer therapy for dystrophic patients. Visualization of the
      pattern of NCAM expression was performed by immunoperoxidase assay, while the
      potential ability to form myotubes was confirmed by the observation of their
      formation within a period of 1 to 2 weeks. The 65% of the CD56+ clones in CFA
      were the same clones that proved to be myogenic with positive immunoperoxidase
      assay and myotube formation. This method avoids the fastidious and costly
      approach of cell sorting (whenever available), avoids contamination hazards due
      to many manipulations of the clones. Moreover this approach leads to a pure
      myoblast population free of any contaminating fibroblast which could contribute
      to connective tissue implement already deleterious in dystrophic patients.

PMID- 7510546
TI  - Low-sulphated oligosaccharides derived from heparan sulphate inhibit normal
      angiogenesis.
AB  - Heparin, with or without the addition of an adrenocorticosteroid, can inhibit
      normal angiogenesis in the chick embryo chorioallantoic membrane. Low- or non
      sulphated heparin fragments also have anti-angiogenic effect. Attempts to define
      a saccharide structure responsible for the anti-angiogenic effect implicated a 
      [GlcA beta 1,4-GlcNAc alpha 1,4]n-sequence. This structure represents the product
      of the initial polymerization reaction in heparin/heparan sulphate biosynthesis.
      It persists in the non-sulphated regions of heparan sulphate and also occurs in
      the Escherichia coli K5 capsular polysaccharide. The K5 polysaccharide, fragments
      thereof down to octasaccharide size and analogous N-acetylated fragments of
      heparan sulphate, all showed anti-angiogenic activity. Hyaluronan, however, with
      the isomeric -[GlcA beta 1,3-GlcNAc beta 1,4]n-structure was inactive. The anti
      angiogenic activity of -[GlcA beta 1,4-GlcNAc alpha 1,4]n-containing saccharides
      was potentiated by the presence of L-iduronic acid and one or two O-sulphate
      groups in the non-reducing-terminal disaccharide unit. The anti-angiogenic effect
      of these non- or low-sulphated saccharides was unaffected by the addition of
      hydrocortisone. Endothelial cell surface-bound heparan sulphate proteoglycans may
      represent a pool of precursors of anti-angiogenic oligosaccharides which may be
      of primary importance in the regulation of angiogenesis.

PMID- 7510547
TI  - Monoclonal antibodies raised against membrane glycoproteins from mouse brain
      recognize N-linked oligomannosidic glycans.
AB  - Monoclonal L3 and L4 antibodies have been shown to recognize carbohydrate
      epitopes on several neural cell adhesion molecules; these epitopes can be
      released by treatment with endoglycosidase H. In the present study, we have
      identified the oligosaccharides released by endoglycosidase H from the cell
      adhesion molecules AMOG and L1 by fast-atom bombardment mass spectrometry as
      being solely of the oligomannosidic type. Using neoglycolipids of oligomannosidic
      glycans, we also report that both antibodies show the highest reactivity with the
      alpha-manno-pentaose Man alpha 1-3-[Man alpha 1-6(Man alpha 1-3)Man alpha 1-6]
      Man, but decreasing reactivity with the alpha-manno-hexaose, heptaose, octaose
      and nonaose glycans. Thus, to our knowledge, we describe here for the first time
      monoclonal antibodies recognizing N-glycosidically linked oligomannosidic
      glycans.

PMID- 7510549
TI  - Surgical treatment of tumors of the cervical spine and first two thoracic
      vertebrae.
AB  - From 1985 through 1990, 19 patients with tumorous conditions of the cervical
      spine and the first two thoracic vertebrae were treated with anterior, posterior,
      or combined anterior/posterior surgical techniques. Breast metastases were by far
      the most common condition (42%). Patients usually experienced severe pain, which
      resisted conservative treatment, sometimes associated with radiculopathies (42%)
      or neurological deficits (31%). To date, the treatment of spinal tumors is only
      palliative, and surgery must be considered for cases with unremitting neck pain,
      major vertebral destruction with loss, or impending loss of cervical spine
      stability and neurological deficits due to local tumor compression. Contrary to
      the commonly used posterior wiring stabilizations, we preferred stabilization
      techniques more closed to those used in traumatology. Our findings suggest
      anterior surgery alone with vertebrectomy and stabilization with plate and bone
      cement for tumors involving only one vertebra and localized between C3 and T1.
      Posterior approach and stabilization is advocated for atlantoaxial lesions. A
      combined anterior and posterior technique should be reserved for extended tumoral
      conditions where an anterior fixation does not offer enough stability or where
      more radical surgery is required. In the present series, immediate good spinal
      stabilization and neck pain relief was obtained in every case, allowing early
      mobilization. Improvement of the neurologic deficit was noted in 65% of our
      patients.

PMID- 7510548
TI  - Structure-function studies on selectin carbohydrate ligands. Modifications to
      fucose, sialic acid and sulphate as a sialic acid replacement.
AB  - The selectins are a family of carbohydrate-binding proteins that have been
      implicated in the initial interaction between leukocytes and the vascular
      endothelium. The three members of this family will bind to the sialyl-Lewisx
      epitope [Sia alpha 2-3 Gal beta 1-4 (Fuc alpha 1-3) GlcNAc] and related
      oligosaccharides. In this report, we examine the molecular details of that
      recognition using synthesized carbohydrates with specific modifications on the
      sialyl-Lewisx epitope. E- and L-Selectin require hydroxyl groups at the 2, 3 and
      4 positions of the fucose residue. P-Selectin, however, requires only the 3
      position hydroxyl group, while tolerating removal of the oxygen at positions 2 or
      4 of fucose residue. Modifications of the glycerol side chain or the N-acetyl
      group of the sialic acid have little effect on the binding of any of the
      selectins. All three selectins bind efficiently to an oligosaccharide with a
      sulphate replacement for the sialic acid [sulpho-Lewisx, or SO4-3Gal beta 1-4
      (Fuc alpha 1-3) Glc-ceramide]. For E-Selectin, binding to sulpho-Lewisx appears
      to be equivalent to binding to sialyl-Lewisx, while for L- and P-Selectin binding
      to the sulphated structure shows characteristics distinct from sialyl-Lewisx
      recognition. Taken together, these data indicate that, while all three selectins
      can recognize sialyl-Lewisx, E-, L- and P-Selectin each display distinct
      carbohydrate ligand preferences.

PMID- 7510550
TI  - Chlorpyrifos in the air and soil of houses eight years after its application for
      termite control.

PMID- 7510551
TI  - Contamination of potato tubers and carrots in Greece with lindane residues.

PMID- 7510552
TI  - Brain met-enkephalin immunostaining after subacute and subchronic exposure to
      benzene.

PMID- 7510553
TI  - Determination of nitrite by high-performance liquid chromatography system with
      electrochemical detector: measurement of nitric oxide synthase activity in rat
      cerebellum cytosol.
AB  - A simple and sensitive assay method for NO synthase activity is described. Using
      glassy carbon as electrode and 30% methanol solution with 10 mM NH4Cl as mobile
      phase, NO2- can be measured without disturbing ECD-detectable substance in NO
      synthase assay mixture. The NO2- production in the assay mixture of rat
      cerebellum: NO synthase increased with protein and in a time-dependent manner.
      The Km value for the substrate, L-arginine, was 1.25 microM. The enzyme activity
      was inhibited in a concentration-dependent manner by a NO synthase inhibitor,
      NNA. The Ki value for NNA was 0.166 +/- 0.060 microM. This ECD-HPLC method for
      determining NO synthase activity has advantages compared with the diazo-coupling
      method of the Greiss reagent and the isotopic method in which the conversion of
      the substrate, [14C]L-arginine, to the product, [14C]L-citrulline is measured; it
      is simple, sensitive and is convenient for studying the NO synthase activity with
      various compounds as the substrate.

PMID- 7510555
TI  - Unambiguous through-bond sugar-to-base correlations for purines in 13C,15N
      labeled nucleic acids: the HsCsNb,HsCs(N)bCb, and HbNbCb experiments.
AB  - A set of three 3D (1H,13C,15N) triple-resonance correlation experiments has been
      designed to provide H1'-H8 intraresidue sugar-to-base correlations in purines in
      an unambiguous and efficient manner. Together, the HsCsNb, HsCs(N)bCb, and HbNbCb
      experiments correlate the H1' sugar proton to the H8 proton of the attached base
      by means of the (H1', C1', N9, C8, H8) heteronuclear scalar coupling network. The
      assignment strategy presented here allows for unambiguous H1'-H8 intraresidue
      correlations, provided that no two purines have both the same H1' and C1'
      chemical shifts and the same C8 and N9 chemical shifts. These experiments have
      yielded H1'-H8 intraresidue sugar-to-base correlations for all five guanosines in
      the [13C,15N] isotopically labeled RNA duplex r(GGCGCUUGCGUC)2.

PMID- 7510554
TI  - Use of blue-sepharose for purification of immunotoxin containing type 1 ribosome
      inactivating protein, gelonin.
AB  - This paper describes a method suitable for purifying immunotoxin containing type
      1 ribosome-inactivating protein, gelonin. The separation of free (unreacted) 80G,
      a monoclonal antibody against alpha-fetoprotein (AFP), from semipurified 80G
      gelonin conjugate was unsuccessful by conventional CM-Sepharose ion-exchange
      chromatography because the isoelectric point of the conjugate did not increase
      enough to reach that of gelonin alone. In contrast, Blue Sepharose affinity
      chromatography could efficiently separate free 80G from the semipurified
      conjugate because the conjugate was bound to the column by its gelonin moiety
      while free 80G was not in buffer containing NaCl of a particular concentration
      range. However, a small amount of conjugate containing gelonin modified with N
      succinimidyl 3-(2-pyridyldithio)propionate, but not with 2-iminothiolane, could
      not bind to the column. The conjugate purified by the use of Blue Sepharose
      showed selective cytotoxicity against AFP-producing human hepatoma cells.

PMID- 7510556
TI  - A computer-based protocol for semiautomated assignments and 3D structure
      determination of proteins.
AB  - A strategy is presented for the semiautomated assignment and 3D structure
      determination of proteins from heteronuclear multidimensional Nuclear Magnetic
      Resonance (NMR) data. This approach involves the computer-based assignment of the
      NMR signals, identification of distance restraints from nuclear Overhauser
      effects, and generation of 3D structures by using the NMR-derived restraints. The
      protocol is described in detail and illustrated on a resonance assignment and
      structure determination of the FK506 binding protein (FKBP, 107 amino acids)
      complexed to the immunosuppressant, ascomycin. The 3D structures produced from
      this automated protocol attained backbone and heavy atom rmsd of 1.17 and 1.69 A,
      respectively. Although more highly resolved structures of the complex have been
      obtained by standard interpretation of NMR data (Meadows et al. (1993)
      Biochemistry, 32, 754-765), the structures generated with this automated protocol
      required minimal manual intervention during the spectral assignment and 3D
      structure calculations stages. Thus, the protocol may yield an approximate order
      of magnitude reduction in the time required for the generation of 3D structures
      of proteins from NMR data.

PMID- 7510557
TI  - Assessing glycosidic linkage flexibility: conformational analysis of the
      repeating trisaccharide unit of Aeromonas salmonicida.
AB  - A detailed conformational analysis was performed for the synthetic branched
      trisaccharide beta-D-ManNAc-(1-->4)-[alpha-D-Glc-(1-->3)]-L-Rha 1 which
      represents the repeating unit of the O-antigenic polysaccharide of Aeromonas
      salmonicida. The study was based on 26 experimental NOE curves from 1D transient
      NOE experiments, employing Gaussian-shaped inversion pulses at 600 MHz. Eight of
      the NOE curves were interglycosidic and thus useful for an analysis of glycosidic
      linkage orientations. Metropolis Monte Carlo (MMC) simulations and minimum-energy
      calculations with the program GEGOP were used to obtain theoretical NOE curves
      which were compared to the experimental ones. MMC simulations with different
      temperature parameters of 310, 600, 900 and 2000 K allowed identification of NOEs
      which are sensitive towards different conformation distributions--not only
      different conformations--at both glycosidic linkages in 1. A comparison of
      trisaccharide 1 with the constituent disaccharides beta-D-ManNAc-(1-->4)-L-Rha 2
      and alpha-D-Glc-(1-->3)-L-Rha 3 revealed effects of branching on glycosidic
      linkage flexibility. A quantitative evaluation was facilitated by the
      introduction of entropy-related flexibility parameters. Our study indicates a
      notable restriction of flexibility, especially at the (1-->3) linkage in 1.
      Although overall flexibility in 1 is reduced as compared to the constituent
      disaccharides 2 and 3, it cannot be neglected altogether. In summary, combined
      transient NOE experiments and MMC simulations provide a simple approach to
      analyse glycosidic linkage flexibility.

PMID- 7510558
TI  - Cloning and characterization of cDNA coding for a new allergen from the house
      dust mite, Dermatophagoides farinae.
AB  - A cDNA clone encoding a new allergen from the Dermatophagoides farinae cDNA
      lambda gt11 library was isolated and sequenced. There was no amino acid sequence
      homology with other known allergens. The gene product, beta-galactosidase fusion
      protein, of the truncated cDNA on blot reacted with IgE in 13 of 43 sera from
      patients allergic to mites. The affinity-purified fusion protein had a potent
      ability to release histamine from washed blood cells of the mite-allergic
      patients. Human specific IgE eluted from the fusion protein band on blots
      recognized a 39-kD component on blots of a mite body extract.

PMID- 7510560
TI  - Eosinophil peroxidase accounts for most if not all of the peroxidase activity
      associated with isolated rat peritoneal mast cells.
AB  - Endogenous peroxidase has been reported in rat peritoneal mast cells and
      granules. Mast cell granules have also been shown to avidly bind exogenous
      eosinophil peroxidase. To examine the possibility that contaminating eosinophil
      peroxidase contributes to the reported rat mast cell peroxidase activity, mast
      cells were increasingly purified over sequential Percoll gradients. Such repeated
      centrifugations did not affect the histamine content of the cells or the
      secretory activity of cells, but the small increases in mast cell purity
      significantly reduced the specific activity of peroxidase; the remaining
      peroxidase activity of the mast cell fraction was in a range that could easily be
      accounted for by a small extent of contamination with eosinophils. An upper limit
      of 0.3 ng peroxidase/10(6) mast cells was determined from these measurements, ten
      times less than the values previously reported. When isolated mast cells were
      deliberately contaminated with soluble eosinophil peroxidase followed by granule
      isolation, the granules showed increased peroxidase activity, confirming the
      ability of mast cell granules to bind exogenous peroxidase.

PMID- 7510559
TI  - Structure of IgE epitopes on a new 39-kD allergen molecule from the house dust
      mite, Dermatophagoides farinae.
AB  - Two IgE epitope sequences comprising Ser56-Pro-Val-Thr-Lys-Arg-Ala-Ser-Leu-Lys
      Ile-Asp-Ser-Lys-Lys70 and Asp104-Val-Glu-Leu-Ser-Leu-Arg-Ser-Ser-Asp-Ile-Ala115
      were identified by deletion analysis of the cDNA encoding a new 39-kD protein of
      mite allergen. A synthetic dodecapeptide corresponding to the latter epitope
      sequence functioned as a monovalent and mite-specific hapten. Replacement of each
      of the 12 amino acid residues with Gly, using site-directed mutagenesis,
      indicated that Arg110 may play a central role in IgE binding. However, the 8
      allergic sera tested exhibited a wide variation in their amino acid residues
      required for reactivity to IgE in allergic sera.

PMID- 7510561
TI  - Immunization of guinea pigs with Treponema pallidum recombinant antigens reveals
      the presence of novel epitopes.
AB  - The DNA technology employed in the construction and purification of recombinant
      antigens has the potential of creating epitopes with specificities other than
      those of native antigens. Such a phenomenon has been observed when guinea pigs
      were immunized with Treponema pallidum recombinant antigens, TmpA and TmpB,
      expressed in Escherichia coli K12. Adsorption of the immune sera with E. coli K12
      and T. pallidum revealed the presence of antibodies directed against epitopes not
      present or exposed in the native antigens of the organisms from which the DNA has
      been cloned.

PMID- 7510562
TI  - Home care of dying patients. Family physicians' experience with a palliative care
      support team.
AB  - Family physicians were asked about their recent experience with caring for dying
      patients at home and for their evaluation of a recently established Palliative
      Care Home Support Team. Ninety-four percent of the respondents had cared for at
      least one dying patient at home during the previous 2 years. About two thirds
      felt comfortable, competent, confident, supported, and in control. One quarter
      felt personally drained by the experience, but almost as many found it personally
      renewing. Of those who had referred patients to the team, two thirds gave the
      team high ratings for being supportive, helpful, quick to respond, and effective
      in communication.

PMID- 7510563
TI  - Chronic hepatitis in haemophilia.
AB  - Chronic hepatitis affects almost all haemophiliacs treated with non-virally
      inactivated clotting factor concentrates. The virus responsible is hepatitis C
      (HCV) and most patients have non-neutralising antibodies with circulating virus.
      Although the majority also have evidence of past infection with hepatitis B, less
      than 5% are chronic carriers of HBsAg. Chronic hepatitis C can be associated with
      severe and progressive liver disease but the development of complications is
      slow. Treatment with recombinant interferon alpha given subcutaneously normalises
      the liver function in 50% of patients, but 50% of responders relapse on stopping
      treatment. Liver transplantation is successful in patients with advanced liver
      disease and it offers the added advantage of phenotypic cure of the haemophilic
      state.

PMID- 7510564
TI  - The development and characterization of an eluted stain assay (ESTA) for the
      insulin-like growth factors.
AB  - An Eluted Stain Assay System (ESTA) has been adapted for the bioassay of the
      insulin-like growth factors, IGF-I and IGF-II. This ESTA is based on the Fischer
      Rat Thyroid cell line FRTL-5 which was grown as uniform, adherent microcultures
      on 96-well microtitre plates. The cells were stimulated with the growth factors
      for 48 h in hormone and serum free conditions. Responses were determined by the
      addition of the tetrazolium salt MTT which was reduced to a purple formazan
      product in a dose related manner. This was directly eluted from the cells and
      measured with a microtitre plate reader. The signal generated was solely
      dependent on metabolic activation of the cells, since no increase in cell numbers
      was detected during the bioassay. The advantages of using this method are its
      sensitivity, precision, specificity, rapidity and high sample throughout. This
      bioassay, which is based on a colorimetric method, is technically convenient
      compared with other systems including the earlier cytochemical bioassays and the
      radioisotopic methods. We have demonstrated that this MTT ESTA provides a useful
      method for the study of complex interactions between IGF-I and IGF-II and their
      related binding proteins and that IGF bioactivity in serum may also be
      investigated using this ESTA bioassay.

PMID- 7510565
TI  - Insulin-like growth factors (IGFs) stimulate and dexamethasone inhibits IGF
      binding protein (BP)-5 expression in a mouse pituitary cell line.
AB  - The mouse pituitary cell line AtT-20 was found to secrete two low MW IGFBPs into
      conditioned medium (CM). The major IGFBP migrated at approximately 29 kDa and a
      minor IGFBP of 24 kDa was also present on western ligand blots (WLB). Both IGFBPs
      were purified from CM by IGF-affinity chromatography followed by reverse phase
      FPLC. N-terminal analysis revealed that the first 10 amino acids of the 29 kDa
      and the 24 kDa IGFBPs were homologous to corresponding sequences of both human
      and rat IGFBP-5 and IGFBP-4, respectively. The 24 kDa IGFBP also crossreacted
      with a new antiserum specific for rodent IGFBP-4. The concentrations of both
      IGFBPs were increased by the addition of IGF-I, IGF-II, or insulin to the cell
      cultures, with IGFBP-5 demonstrating the greatest hormonal stimulation. The
      effects of IGF-I on IGFBP-5 expression were both time and dose dependent, with
      IGF-I being more potent than IGF-II, and IGF-II more potent than insulin. The
      relative potencies of these hormones in stimulating IGFBP-5 production were
      consistent with the peptides acting through the type-I IGF receptor. Similarly,
      the IGF-II analog [Leu 27]-IGF-II, which has very low affinity for the type-I
      receptor, only slightly stimulated an increase in IGFBP-5. Addition of
      dexamethasone to the cultures decreased both basal and IGF-stimulated IGFBP-5
      production. Northern blotting demonstrated that IGF-I increased the expression of
      the mRNA for IGFBP-5, whereas dexamethasone decreased it. Together, these data
      suggest that the IGFs can increase IGFBP-5 production at both the protein and
      mRNA level.

PMID- 7510566
TI  - Postextrasystolic ischemic T wave. A possible silent ischemia.
AB  - Postextrasystolic potentiation may produce in some situations a negative T wave.
      This situation is presented in two cases, and it is assumed that this phenomenon
      may be considered as silent myocardial ischemia.

PMID- 7510567
TI  - Effects of various esters of trans-4-guanidinomethylcyclohexanecarboxylic acid,
      trypsin inhibitors, on the growth of Bacillus subtilis.
AB  - Various aromatic esters of trans-4-guanidinomethylcyclohexanecarboxylic acid
      (GMCHA), trypsin inhibitors, strongly inhibited the growth of Bacillus subtilis
      558 and their effects were markedly affected by the species of substitution on
      the phenyl nucleus of the GMCHA phenyl esters. 4-tert-Butylphenyl ester of GMCHA
      (GMCHA-OPhtBu), a representative of various GMCHA esters, dose-dependently
      inhibited the growth of B. subtilis and DNA, RNA and protein syntheses in the
      cells. The growth inhibition was preceded by suppressive effect of GMCHA-OPhtBu
      on DNA synthesis. These results suggested the possible involvement of a trypsin
      like proteinase in DNA synthesis. A trypsin-like proteinase was partially
      purified from B. subtilis 558 by DEAE-cellulose column chromatography, ammonium
      sulfate fractionation and successive chromatographies on Sephadex G-200, phenyl
      Sepharose CL-4B, L-arginine-Sepharose 4B and Sephadex G-200 columns. The
      properties were compared with those of proteinase In, which momentarily appears
      just before the onset of DNA synthesis and seems to participate in the initiation
      of DNA replication, and which was purified from E. coli K-12 IAM 1264. The
      properties of the proteinase from B. subtilis 558 were similar to proteinase In,
      however, the molecular mass (110000) was different from that of the latter
      (66000). Various GMCHA esters strongly inhibited the proteinase activity and the
      order of the effects was closely correlated with that on the cell growth. The
      proteinase was tentatively called subtilis proteinase In.

PMID- 7510568
TI  - Interaction of eosin-5-maleimide with band 3 of human erythrocytes.
AB  - The interaction between EMI (eosin-5-maleimide) and band 3 of human erythrocytes
      was studied under various conditions. It was found that the effects of the ionic
      strength on the EMI-band 3 interaction strongly depended on pH. At pH 6.0, the
      ionic strength had remarkable effects on the EMI-bound band 3, whereas at pH 7.4,
      the EMI-band 3 interaction was independent of ionic strength. From the change in
      the circular dichroism spectra of the EMI-bound band 3, it was revealed that the
      conformation or the structure of the EMI-binding sites in the cytoplasmic domain
      of band 3 was strongly dependent on ionic strength. The thermodynamic parameters
      for the covalent-binding between EMI and band 3 were calculated on the basis of
      the difference spectra of the EMI and ghost system. The values of activation
      energy and activation entropy change at pH 6.0 were extraordinarily small
      compared with those values at pH 7.4. These findings represent the
      characteristics of the EMI-binding sites in the cytoplasmic domain of band 3. The
      interaction of EMI with an isolated fragment of the cytoplasmic domain, 43k
      fragment, was also examined. The circular dichroism spectra of the EMI-bound 43k
      fragments was significantly different from those of the EMI-bound band 3. This
      may indicate that the quaternary structure of the EMI-binding site in the
      cytoplasmic domain of band 3 is altered by an allosteric connection with the
      membrane-spanning domain of band 3. Further, from the pH titration of the 43k
      fragment, it was suggested that lysine residues are responsible for the ionic
      interaction between EMI and the 43k fragment.

PMID- 7510569
TI  - [Results of the surgical treatment of benign hypertrophy of the prostate].

PMID- 7510571
TI  - Neonatal sciatic nerve section results in a rearrangement of the central
      terminals of saphenous and axotomized sciatic nerve afferents in the dorsal horn
      of the spinal cord of the adult rat.
AB  - Previous studies have shown that following neonatal peripheral nerve injury,
      adjacent intact myelinated and unmyelinated primary afferents sprout into the
      central denervated terminal area. The present study investigates this in more
      detail and goes further, to study the fate of the central terminals of the
      surviving axotomized primary afferent neurons. Bulk labelling of the sciatic and
      saphenous nerves with horseradish peroxidase conjugated to choleragenoid (B-HRP),
      to label the A fibres, or wheatgerm agglutinin (WGA-HRP), to label C fibres were
      employed to investigate the central consequences of sciatic nerve section and
      ligation on the day of birth, in adult rats. Bulk labelling of the axotomized
      sciatic or intact saphenous nerve with either tracer and comparison with
      contralateral controls revealed alterations to the terminal field. The intact
      saphenous nerve terminal field expanded caudally from mid L4 to the L4-L5
      boundary when labelled with WGA-HRP and to the sacral cord when labelled with B
      HRP. Labelling the axotomized sciatic nerve with either tracer revealed little
      change in the overall somatotopic organization of central terminals, although
      labelling was less intense compared to control nerves and more variable with WGA
      HRP. Invasion of the substantia gelatinosa (SG) by axotomized A fibres was
      observed in segments L3-5, into the area occupied by axotomized C fibres. This
      area was also invaded by intact saphenous A fibres in the L4-5 segments. These
      results demonstrate that following neonatal nerve section: (i) axotomized primary
      afferents are able to retain a 'normal' somatotopic map in the rostrocaudal
      plane; (ii) both A and C fibres from adjacent intact nerves sprout into the
      denervated territory, but A fibres sprout further caudally; (iii) axotomized A
      fibres and invading intact A fibres both sprout dorsally into denervated SG. As a
      result, there is considerable overlap between nerve territories in denervated
      spinal cord, suggesting that competition for laminar termination sites exists
      between A and C fibres and also between axotomized and intact primary afferents.

PMID- 7510570
TI  - aFGF, bFGF and flg mRNAs show distinct patterns of induction in the hippocampus
      following kainate-induced seizures.
AB  - We report that kainic acid-induced seizures lead to marked increases in mRNAs
      encoding basic and acidic fibroblast growth factors (bFGF and aFGF, respectively)
      and flg, one of their receptors, in the rat hippocampus. Anticonvulsant
      pretreatment inhibits the up-regulation of these mRNAs. The observed increase in
      flg mRNA levels involves the pyramidal cells of all hippocampal subfields and the
      granular cells of the dentate gyrus. The increased expression of aFGF and bFGF
      mRNAs is limited to neuron populations that are resistant to seizure-induced
      injury, the granular cells of dentate gyrus and pyramidal cells of CA1 region,
      respectively. The results suggest that the increase in the FGFs and flg may play
      pivotal roles in neuron survival and in long-term changes occurring in the
      hippocampus following seizure activity.

PMID- 7510572
TI  - The pathophysiological changes in the bladder obstructed by benign prostatic
      hyperplasia.
AB  - None of the hypotheses to explain the genesis of obstructed detrusor instability
      covered in this report provide a satisfactory explanation, by themselves, for the
      condition. While symptoms associated with prostatic obstruction are a common
      cause of patient referral to a urologist, all therapeutic advances so far have
      been directed towards the relief of bladder outflow resistance. It is possible
      that pharmacotherapy, for example, with drugs which stabilize muscle cell
      membranes and autonomically active drugs such as alpha 1-antagonists, possibly
      combined with anticholinergics, will have a therapeutic role in the treatment of
      obstructive detrusor instability. Further studies of obstructed human bladder are
      necessary to investigate the importance of changes in receptor density, affinity
      and distribution, agonist release and degradation and subsequently the
      ultrastructural and physiological alterations following the relief of
      obstruction.

PMID- 7510573
TI  - The Urolume as a means of treating urinary outflow obstruction and its impact on
      waiting lists.
AB  - OBJECTIVE: To evaluate the effectiveness of the prostatic stenting device--the
      Urolume--both in terms of relief from urinary outflow obstruction and as a means
      of reducing waiting lists. PATIENTS AND METHODS: A group of 70 men from the long
      term waiting list were chosen for this study. The Urolume, a mesh tube of
      biomedical superalloy, was successfully introduced in 60 of these patients. The
      majority had the procedure performed as a day case, under a general anaesthetic.
      RESULTS: Seventy-two per cent of patients were symptomatically better when
      assessed at 6 weeks and their mean peak urinary flow rates had doubled. Early
      problems included haematuria, urge incontinence and dysuria. Stent displacement
      necessitating removal occurred in 10 patients. CONCLUSION: This technique offers
      the surgeon a quick and atraumatic method of relieving urinary outflow
      obstruction. There are, however, a number of problems associated with this
      technique which will probably be overcome by modification to the Urolume. As a
      result of our project, the waiting time for prostatic surgery was reduced from 3
      years to under 2 years.

PMID- 7510574
TI  - Occupancy of central neurotransmitter receptors by risperidone, clozapine and
      haloperidol, measured ex vivo by quantitative autoradiography.
AB  - Risperidone (Risperdal) is a novel antipsychotic drug, with beneficial effects on
      both positive and negative symptoms of schizophrenia, and with a low incidence of
      extrapyramidal side effects (EPS). These particular properties have been
      attributed to the predominant and very potent serotonin 5-HT2 receptor antagonism
      of the drug combined with less potent dopamine D2 antagonism. In order to provide
      data on the degree to which various central neurotransmitter receptors are
      occupied in vivo, we performed ex vivo receptor occupancy studies with
      risperidone in comparison with clozapine and haloperidol in rats and guinea pigs.
      Various types of receptors, to which the compounds were known to bind to in
      vitro, were investigated precisely using receptor autoradiography in sections of
      the same rat brain except for histamine H1 receptors that were measured in the
      guinea-pig cerebellum. Risperidone (2 h after s.c. treatment) occupied 5-HT2
      receptors at very low doses (ED50 = 0.067 mg/kg). Nearly full occupancy (> 80%)
      was achieved before H1, D2, alpha 1 and alpha 2 receptors became occupied (ED50 =
      0.45, 0.66, 0.75 and 3.7 mg/kg, respectively). Clozapine displayed occupancy of
      H1 and alpha 1 receptors at low doses (ED50 = 0.15 and 0.58 mg/kg, respectively)
      and of 5-HT2, 5-HT1C, D2, alpha 2, cholinergic muscarinic and 5-HT1A receptors at
      higher doses (ED50 = 1.3, 1.8, 9.0, 9.5, 11 and 15 mg/kg, respectively).
      Haloperidol occupied D2 and alpha 1 receptors at low doses (ED50 = 0.13 and 0.42
      mg/kg, respectively) and 5-HT2 receptors at a higher dose (ED50 = 2.6 mg/kg).
      Occupancy of receptor types occurred with similar ED50-values in various brain
      areas, e.g. D2 receptors in striatum and mesolimbic areas. The ED50-values for
      the ex vivo measured occupancy of 5-HT2 and D2 receptors were in good agreement
      with ED50-values for functional effects putatively mediated by these central
      receptors. The dose-dependent occupancy of D2 receptors proceeded more gradually
      with risperidone (slope in the caudate-putamen: 0.85) than with clozapine (slope:
      1.44) or haloperidol (slope: 1.51). It has previously been suggested that partial
      D2 receptor occupancy may suffice to control the positive symptoms of
      schizophrenia, whereas higher D2 receptor occupancy would induce extrapyramidal
      symptoms (EPS). The dose ratio for high (75%) vs. low (25%) D2 receptor occupancy
      in the caudate-putamen, was 37.3 for risperidone, 8.4 for clozapine, and 7.9 for
      haloperidol.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7510575
TI  - Spinothalamocortical projections to the secondary somatosensory cortex (SII) in
      squirrel monkey.
AB  - Anterograde labeling of the cervical spinothalamic tract was combined with
      retrograde labeling of thalamocortical cells projecting to the hand region of the
      second somatosensory cortex (hSII) to identify likely sites in the thalamus for
      processing and transmitting nociceptive information to hSII. Anterograde labeling
      of terminals was done with 2% WGA-HRP injections in the cervical enlargement;
      thalamocortical cells were retrogradely labeled with fluorescent tracers. In one
      experiment, the contralateral primary somatosensory cortex hand region (hSI) was
      injected to provide a direct comparison with hSII thalamic label. Both labeled
      cells and terminal-like structures were visualized in single thalamic sections
      and their numbers and positions quantitatively analyzed. The number of labeled
      cells within 100 microns from the STT terminals were counted as overlapping
      cells. Four thalamic nuclei, ventroposterior inferior (VPI), ventroposterior
      lateral (VPL), posterior nucleus (PO) and centrolateral nucleus (CL) combined to
      contain 86.5% of all hSII-projecting overlapping cells. Of all hSII-projecting
      thalamic overlapping cells, VPI contained the largest number (36.4% of the total)
      followed by the anterior portion of the posterior nuclear complex (POa; 20.4%),
      VPL (18.3%) and CL (11.4%). Results of the hSI injection show a different pattern
      of overlap in agreement with our earlier study. The relative distribution of
      overlapping cells was dependent on the antero-posterior position of the SII
      injections. The most anterior injections resulted in small numbers of labeled
      cells, with the majority of overlapping cells located in PO and CL. The more
      posterior injections resulted in overlapping cells mainly in VPI and
      VPL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510576
TI  - Biochemical evidence of angiotensin II-like peptides and proteins in the brain of
      the rhynchobdellid leech Theromyzon tessulatum.
AB  - The peptides contained in neurons localized in the brain of the leech Theromyzon
      tessulatum (Hirudinae, Rhynchobdellida) and showing an immunopositive reaction
      with an antibody directed against angiotensin II (AII), were purified by reversed
      phase HPLC. Three AII-like peptides (P1, P2 and P3) which exhibited the same
      retention times and chromatographic behaviors as synthetic AVII (fragment 6-8 of
      AII), AIV (fragment 3-8 of AII) and AII, respectively, were resolved in brain
      extracts. An identification of the proteins immunoreactive to an anti-AII was
      performed at the level of both brain extracts and in vitro brain-translated RNA
      products. The protein detected at the level of the brain extracts (of a molecular
      mass of approximately 18 kDa) is multipeptidic as it is also recognized by two
      other antisera, a polyclonal one directed against gamma-MSH and a monoclonal one
      (Tt159) raised against a leech brain epitope. It could be the pro-AII-like
      precursor. The protein detected at the level of in vitro brain-translated RNA
      products (of a molecular mass of approximately 19 kDa) could be the prepro-AII
      like precursor.

PMID- 7510577
TI  - Differential distributions of the NMDA receptor channel subunit mRNAs in the
      mouse retina.
AB  - In the retina, the epsilon 2 and zeta 1 subunit mRNAs of the NMDA receptor
      channel were expressed from embryonic stages and found in ganglion cell layer and
      whole layer of inner nuclear layer at postnatal day 21 (P21). The epsilon 1
      subunit mRNA appeared postnatally and was distributed in ganglion cell layer and
      an inner third of inner nuclear layer at P21. These findings suggest that
      molecular organization of the NMDA receptor channel may alter during the retinal
      development.

PMID- 7510578
TI  - Prolonged infusion of fluorinated pyrimidines in gastrointestinal malignancies: a
      review of recent clinical trials.

PMID- 7510579
TI  - Studies of O-specific polysaccharide chains of Pseudomonas solanacearum
      lipopolysaccharides consisting of structurally different repeating units.
AB  - The structures of the O-antigenic polysaccharide chains of lipopolysaccharides of
      a number of Pseudomonas solanacearum strains were elucidated mainly with the help
      of methylation analysis and 13C NMR spectroscopy, including a computer-assisted
      13C NMR-based analysis. Six structurally distinct but related polysaccharides
      were identified. They have a backbone which is built up of three L
      rhamnopyranosyl residues and one 2-acetamido-2-deoxy-D-glucopyranosyl residue,
      and is unsubstituted or substituted with a residue of L-xylopyranose or L
      rhamnopyranose as a monosaccharide side chain. The lipopolysaccharides of most of
      the strains contain polysaccharide chains consisting of at least two structurally
      different types of repeating units. Three of the polysaccharides are common to
      more than one strain.

PMID- 7510580
TI  - Two different spatiotemporal patterns for Ca2+ oscillations in pancreatic acinar
      cells: evidence of a role for protein kinase C in Ins(1,4,5)P3-mediated Ca2+
      signalling.
AB  - The oscillations in cytosolic Ca2+ evoked in pancreatic exocrine acinar cells by
      submaximal concentrations of the two phosphoinositidase-coupled agonists
      acetylcholine (ACh) and cholecystokinin octapeptide (CCK-8) have very different
      temporal patterns. In the present study we use digital video imaging of Fura-2
      fluorescence to map the spatial distribution of Ca2+ during the oscillating
      responses to these two agonists. The spatial patterns induced are very different
      for each of these agonists. ACh oscillations are sinusoidal and initiated at the
      secretory pole of these morphologically and functionally polarized cells. As they
      spread across the cell, pronounced gradients in Ca2+ develop that persist
      throughout the oscillating response. CCK-8 induces a series of discrete Ca2+
      transients of longer duration and lower frequency. These elevations in Ca2+ arise
      slowly, throughout the cells and without any detectable gradients in Ca2+. We
      consider that the different spatiotemporal patterns can be explained on the basis
      of a physiologically relevant interaction between Ins(1,4,5)P3 and protein kinase
      C in second messenger-mediated Ca2+ signalling.

PMID- 7510581
TI  - The human 4F2 antigen: evidence for cryptic and noncryptic epitopes and for a
      role of 4F2 in human T lymphocyte activation.
AB  - T lymphocyte activation can be triggered through multiple distinct, but
      functionally related, pathways. Murine monoclonal antibodies (mAbs) have been
      used to characterize the surface components of several of these pathways, as well
      as structures whose function is not yet known. One such cell surface structure is
      the heterodimeric 4F2 antigen, which is expressed on activated and proliferating
      cells. Two new mAbs that recognize the heavy chain of the 4F2 antigen have been
      produced in our laboratory. One antibody, UM7F8, is comitogenic with soluble anti
      CD2 and immobilized (but not soluble) anti-CD3 mAbs. The second antibody, termed
      UM2G12, appears to recognize a cryptic epitope on the 4F2 heavy chain and is not
      comitogenic for T cells. In view of the functional effects seen with UM7F8, and
      the highly regulated expression of the 4F2 antigen, it seems likely that 4F2 has
      a specific role in T cell development and activation.

PMID- 7510582
TI  - Interleukin-10 production by splenic CD4+ cells and cell subsets from young and
      old mice.
AB  - We have examined whether aging is accompanied by changes in the capacity of CD4+
      cells to produce IL-10, a potent immunoregulatory cytokine. Splenic CD4+ cells
      from young-adult and old C57BL/6NNia mice were stimulated in vitro with
      immobilized anti-CD3 epsilon mAb and were monitored for the release of IL-10 in
      short-term (3-day) cultures. In both age groups, detectable IL-10 accumulation in
      culture supernatants was stimulation dependent and reached a maximum level on Day
      3. However, the peak IL-10 level in the old group was approximately 10-fold
      higher than that in the young-adult group. This age-associated difference in IL
      10 production was also evident in the analysis of IL-10 mRNA levels in stimulated
      CD4+ cells. In contrast to these findings, the analysis of S-phase activity in
      the stimulated cell cultures revealed an age-related decline in this aspect of
      the cellular response. In studies on CD4+CD44lo and CD4+CD44hi subsets isolated
      from mice of various ages, we found that measurable IL-10 production segregated
      entirely with the CD44hi population, regardless of donor age. Taken together, our
      data suggest that the capacity for IL-10 synthesis by the splenic CD4+ cell pool
      is increased with age, and that the age-related shift toward a predominance of
      CD4+CD44hi cells in the peripheral tissues accounts for this quantitative change
      in IL-10 gene expression.

PMID- 7510583
TI  - T cell activation is not a prerequisite for peripheral tolerance induction to Mls
      1a.
AB  - T cell interaction with endogenous retroviral superantigens in vivo results in
      either deletion of the reactive T cells or their transition to a state of
      unresponsiveness. We show here that introducing cells expressing the endogenous
      superantigen Mls 1a into an Mls 1b environment results in the induction of an
      anergic state with little or no depletion of V beta 6/CD4+ T cell from the
      peripheral T cell repertoire. Removal of B cells from the priming innoculum
      abrogates the induction of tolerance, indicating that presentation of Mls 1a by B
      cells induced the tolerance observed. The tolerant T cells are unable to respond
      to either presentation of Mls 1a on spleen cells or cross-linking anti-T cell
      receptor antibody in vitro. Although large increases in the cell size and numbers
      of reactive T cells are observed 2-3 days after priming with Mls 1a-presenting
      cells, this activation is not a requirement for the induction of tolerance
      because irradiated Mls 1a-presenting cells retained the ability to induce
      tolerance without these changes in the reactive T cell population. Furthermore,
      providing host T cells with Mls 1a and a costimulatory signal, in the form of
      high levels of the B7 determinant on the donor cells, did not circumvent the
      induction of tolerance. Collectively, these results indicate that the transition
      to an anergic state following interaction with endogenous superantigen in vivo is
      not dependent upon the activation of the reactive T cells.

PMID- 7510584
TI  - Analysis of the functional potential of mouse CD4+ T cells using a high
      efficiency cloning system.
AB  - In order to examine the functional potential of individual mouse CD4+ T cells
      selected, as far as possible, in a random manner, a high-efficiency cloning
      system driven by Con A was utilized. Under optimal conditions, cloning
      efficiencies of CD4+ cells of about 50% were regularly attained. Although the
      relative proportion of different TH subsets varied depending on the cloning
      conditions, the high cloning efficiency, coupled with the analysis of over 100
      clones, allowed important conclusions to be drawn regarding the general
      construction of the mouse CD4+ T cell repertoire. (1) At least 50% of all mouse
      splenic CD4+ T cells have the potential to produce IL4, supporting the view that
      TH subsets arise by an instructional or regulatory mechanism, rather than by
      selection. (2) TH0 clones produce amounts of IL2 and IL4 similar to those
      produced by TH1 and TH2 clones, respectively, but secrete much lower quantities
      of IFN than TH1 clones. (3) A large proportion of TH2 clones secrete measurable
      amounts of IFN. (4) Lymphokine secretion patterns among CD4+ T cells are clearly
      not determined at random, since IL2 production is always accompanied by IFN
      production. (5) At least 50% of all mouse splenic CD4+ T cells have cytolytic
      capacity as shown by killing in a 20-hr assay, but only a proportion can also
      kill in 4-hr assays. Killing in 4-hr assays was strongly correlated with the
      ability to secrete IL2, regardless of whether IL4 was also secreted.

PMID- 7510585
TI  - Further characterization of CD82/IA4 antigen (type III surface protein): an
      activation/differentiation marker of mononuclear cells.
AB  - The mononuclear cell surface protein IA4 was originally identified in our lab
      using a mAb selected because of its strong reactivity with three lymphoblastoid
      variant cell lines which are HLA class I deficient, are LAK susceptible, and form
      a high number of conjugates with LAK effectors. We previously cloned the cDNA of
      the IA4 protein, coding for a 267-amino-acid type III integral membrane protein,
      with four transmembrane domains and three possible N-glycosylation sites. The IA4
      protein belongs to the tetra span transmembrane (TST) new family of surface
      molecules, which also includes CD9, CD37, CD53, CD63, and TAPA-1. IA4 antigen was
      recently recognized as belonging to a new cluster of differentiation CD82
      (International CD Workshop, Boston 1993). The IA4 antigen expression pattern at
      the surface of immune cells from normal donors was studied. On T lymphocytes, IA4
      was barely detectable on resting cells and increased 3.5- to 7-fold following PHA
      or PHA+PMA stimulation. This IA4 increased expression is correlated with the
      morphologic change in blast cells and with the expression of activation markers
      such as CD2 and MHC class II antigens, therefore suggesting that IA4 is an
      activation marker on T lymphocytes. The expression of IA4 was low on circulating
      resting monocytes collected by elutriation. However, these monocytes, cultured in
      medium alone or with GM-CSF, acquired the morphology of macrophage and
      simultaneously overexpressed MHC Class II, CD14, and IA4 antigens, suggesting
      that IA4 is a differentiation marker for macrophages, whatever the culture
      conditions, either adherent (plastic culture dishes) or nonadherent (Teflon
      culture bags). IA4 stable transfectants of the murine mastocytoma cell line P815
      were obtained and used to generate a new mAb. Competitive epitope binding studies
      have shown that IA4 antigen presents a dominant epitope recognized by most of the
      mAb prepared either in our lab or elsewhere. This dominant epitope is not shared
      by any of the other antigens of the TST family. Using this new mAb we were able
      to biochemically characterize the IA4 antigen as a 28-kDa protein, highly N
      glycosylated with different patterns on various cells.

PMID- 7510586
TI  - T-helper lymphocytes specific for myelin basic protein: activation-induced
      refractoriness of IL-2 production pathways augments an anti-CD4-mediated
      proliferative deficit.
AB  - Cloned and uncloned lines of encephalitogenic rat T cells produce IL-2 when
      activated with myelin basic protein (MBP) in the presence of irradiated
      splenocytes (SPL). Although these T cells use IL-2 as a primary mediator of
      autocrine growth, regulatory mechanisms controlling production of IL-2 have yet
      to be fully defined. This study shows that T cells reactivated within
      approximately 7 days of a prior activation were refractory to the reinduction of
      MBP-stimulated IL-2 production. In contrast, T cells rested for > 7 days regained
      the ability to produce optimal levels of IL-2 during activation with MBP.
      Cultures containing both activated and resting T cells responded to MBP by
      producing levels of IL-2 that were similar to those obtained from control
      cultures of resting T cells. The lack of IL-2 production during this refractory
      phase was associated with lowered responsiveness to MBP in proliferative assays
      as evidenced by right-shifted dose-response curves. However, this refractory
      phase did not affect the magnitude of responses elicited by optimal
      concentrations of MBP. The dissociation of proliferation from IL-2 production
      suggested parallel pathways of autocrine growth. Indeed, anti-MBP-proliferative
      responses were mediated by two distinct mechanisms distinguished by differential
      susceptibility to the anti-CD4 mAb W3/25. The W3/25-sensitive proliferation was
      desensitized in chronically activated T cells as well as in T cells activated
      once in the presence of the anti-CD4 mAb W3/25. Conversely, MBP responsiveness of
      W3/25-insensitive proliferation was unchanged by both chronic activation and by a
      prior activation in the presence of W3/25. In cultures of T cells recently
      activated by MBP in the presence of W3/25, the use of nonirradiated SPL rather
      than irradiated SPL reversed W3/25-mediated tolerance but did not restore MBP
      stimulated IL-2 production. In summary, this study reveals mechanisms whereby the
      engagement of TcR and CD4 negatively regulates subsequent responsiveness of IL-2
      production pathways and thereby impairs restimulation of IL-2-dependent
      proliferation by MBP-specific T-helper cells.

PMID- 7510587
TI  - Status epilepticus results in reversible neuronal injury in infant rat
      hippocampus: novel use of a marker.
AB  - Despite ready induction of severe limbic status epilepticus by systemic kainic
      acid (KA) in infant rats, excitotoxic neuronal injury has not been observed. The
      mechanisms of this resistance of the immature hippocampus to excitotoxicity are
      unknown. Acid fuchsin stain has been used as a marker of irreversibly injured
      neurons in the adult brain. We speculated that the dye might map reversibly
      injured neurons in the infant. Subsequent to KA-induced status epilepticus in 11
      day-old rats, acid fuchsin stain was evident in the hippocampal CA3, CA1, dentate
      gyrus and hilus by 24 h, peaked at 48 h and disappeared by 6 days, without
      evidence for neuronal loss. Acid fuchsin may be a useful tool for delineating the
      distribution of reversibly injured immature neurons in experimental seizure
      paradigms.

PMID- 7510588
TI  - Ontogeny of the distribution of tachykinins in rat cerebral cortex:
      immunocytochemistry and in situ hybridization histochemistry.
AB  - Tachykinins in the mammalian brain are derived from two genes: preprotachykinin
      A, encoding substance P and neurokinin A, and preprotachykinin B, encoding
      neurokinin B. Using immunocytochemistry and in situ hybridization histochemistry,
      we have investigated the ontogeny and distribution of substance P and neurokinin
      B in various cortical areas of rat cerebrum at different prenatal and postnatal
      ages. Preprotachykinin A mRNA-positive and -immunoreactive cells were first
      detected at birth and were abundant in layer VIb and the adjacent white matter in
      the cingulate and frontal cortices. By postnatal day 5, the numbers of substance
      P-expressing cells were diminished dramatically in those layers. However, their
      number gradually increased and spread out laterally to cover parietal and
      temporal cortices from P5 to P15 in layer V. At these stages, cells were also
      observed in layer II, although fewer in number. The number of substance P mRNA
      positive neurons and substance P-immunoreactive cells decreased gradually from
      P10 and P15 onward, respectively. On the other hand, expression of neurokinin B,
      as detected by in situ hybridization histochemistry or immunocytochemistry, was
      not evident until P10. Neurons expressing this tachykinin were concentrated in
      layer II, and to a lesser extent in layers V and VI. This pattern of distribution
      was retained through P45. The present data show a marked difference between these
      two tachykinins in onset and trends of development, suggesting functional
      independence of these two tachykinins in the cerebral cortex.

PMID- 7510589
TI  - Analysis of pyruvate dehydrogenase expression in embryonic mouse brain:
      localization and developmental regulation.
AB  - Brain malformations and neurological dysfunctions are often seen in pyruvate
      dehydrogenase (PDH) deficient patients. To understand these clinical
      presentations, we have analyzed the localization and developmental expression of
      PDH in the embryonic mouse nervous system. Immunostaining was performed to
      localize PDH E1 alpha protein. PDH activities were measured before and after
      activation. PDH E1 alpha mRNA levels were quantitated by reverse transcriptase
      polymerase chain reaction. Abundant PDH E1 alpha protein was localized in the
      central nervous system and other neural tissues in embryos at embryonic day (E)
      11 onwards. The PDH activity was very low in E9 brain and it increased
      continuously until the end of gestation. The proportion of active form of PDH
      increased significantly in E15 brain. Analysis of the PDH E1 alpha mRNA showed
      that only the X-linked form of the gene was transcribed. The overall mRNA level
      of E9 brain was approximately 93% of the adult value. It decreased gradually
      during embryogenesis. A large increase took place at the end of gestation. The
      mRNA level of PDH was approximately 100 times higher than that of the acetoacetyl
      CoA thiolase gene. These results suggest that PDH E1 alpha transcripts of E9
      brain are not translated at a high level. The appearance of PDH activity and its
      increase during E11 and E15 are mainly due to increased levels of translation and
      activation of PDH. Increased PDH activity at the end of gestation is attributed
      to an increase in transcription. Our data to a large extent explain pathological
      presentations in PDH E1 alpha deficient patients with congenital brain disorders.

PMID- 7510590
TI  - Evaluation of Ciba Corning ACS:180 automated immunoassay system.
AB  - We evaluated the technical performance of the Ciba Corning ACS:180 automated
      immunoassay system for the following analytes: thyroid-stimulating hormone, free
      thyroxine, luteinizing hormone, follicle-stimulating hormone, prolactin, human
      chorionic gonadotropin, carcino-embryonic antigen, and prostate-specific antigen.
      The characteristics evaluated were: precision, carryover, linearity, lower limit
      of detection, analytical interferences, and comparison with other methods.
      Satisfactory results were obtained in the within-run and between-run precision
      studies. Neither sample nor reagent carryover was found for any assay. The range
      of linearity was acceptable. For some of the assays evaluated, the lower limit of
      detection was better than that claimed by the manufacturer. Correlation between
      ACS:180 methods and compared methods was adequate. We conclude that the ACS:180
      offers good reliability, practicability, and performance capabilities.

PMID- 7510591
TI  - Demonstration and minimization of serum interference in flow cytometric two-site
      immunoassays.
AB  - The ability of serum factors to cross-link labeled mouse monoclonal antibody
      (mAb) of irrelevant specificity (mAb FN61, subclass IgG1) to different particle
      types coated with sheep IgG, bovine gamma-globulin, or mAb FN61 was measured
      simultaneously by flow cytometry. Significant interference with mAb FN61-coated
      particles was detected in 53 of 101 sera. Of the 30 sera showing the most
      pronounced interference, 23 were characterized by an even stronger cross-linking
      to particles coated with bovine gamma-globulin. These were designated type 1
      sera. Seven sera, designated type 2, displayed a dominant interference with the
      mAb FN61-coated particles. The interference reaction in the two serum types was
      characterized by different kinetics, dependence on particle concentration, and
      response to blocking agents. The interference was minimized by addition of 500
      micrograms of bovine gamma-globulin and 50 micrograms of mAb HH1 (IgG1) of
      irrelevant specificity per 10 microL of serum sample in a final assay volume of
      100 microL.

PMID- 7510592
TI  - Simple method for determining specific binding capacity of vitamin D-binding
      protein and its use to calculate the concentration of "free" 1,25
      dihydroxyvitamin D.
AB  - A quantitative method to measure the specific binding capacity for 25
      hydroxyvitamin D (25D-binding capacity) is described that resembles the
      qualitative "T3-uptake" assay. Patient's serum or standard (10 microL) is mixed
      with 0.5 mL of reagent containing 0.5 mumol/L 25-hydroxyvitamin D [25(OH)D3] plus
      3000 counts/min [3H]25(OH)D3. After 0.5 h at 37 degrees C, the samples are
      treated with dextran/charcoal on ice for 1 h and centrifuged. The radioactivity
      of the bound tracer in the supernate is counted. Calibration is linear to
      approximately 10 mumol/L. 25D-binding capacity in reference-group serum samples
      was 4.33 (0.58 SD) mumol/L. The relationship between the inverse of 25D-binding
      capacity and the free fraction of [3H]1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
      measured by ultrafiltration isodialysis was essentially linear (r = 0.934, P <
      0.0001). Given this relationship, the calculated free fraction of 1,25(OH)2D3
      equals 4.88 x 10(-3)/25D-binding capacity. The 25D-binding capacity was
      significantly lower in newborn babies and in adults with liver disease, and was
      increased during pregnancy (P < 0.01 for each). This method is applicable to
      situations where the biologically available concentration of 1,25(OH)2D is of
      interest.

PMID- 7510593
TI  - Microparticle-enhanced nephelometric immunoassay of anti-thyroid peroxidase
      autoantibodies in thyroid disorders.
AB  - Crude thyroid peroxidase extracted from human thyroid microsomes was covalently
      bound onto polyacrylic and polyfunctional copolymerized microparticles. We
      observed agglutination of the thyroid peroxidase-microparticle conjugate with 13
      monoclonal antibodies (mAbs) specific for epitopes on four different antigenic
      domains of human thyroid peroxidase (TPO; EC 1.11.1.7), after addition of anti
      mouse immunoglobulins. We quantified agglutination by measuring with a specially
      designed nephelometer the light scattered by the conjugates. This allowed us to
      develop a microparticle-enhanced nephelometric immunoassay for human anti-TPO
      autoantibodies (aAbs) with defined epitopic specificity, based on the ability of
      aAbs to inhibit mAb-induced agglutination. Applied to patients with autoimmune
      thyroid diseases, this assay confirmed the polyclonality of anti-TPO aAbs and
      their preferential reactivity toward epitopes located on the A and B antigenic
      domains of the TPO molecule. The same specificities seem to be present in
      patients with Hashimoto thyroiditis or Graves disease.

PMID- 7510594
TI  - Biological variation in urine samples used for analyte measurements.
AB  - To determine the influence of biological variation on the reliability of data
      from different types of urine specimens, we measured nine analytes in first
      morning, randomly collected, and 24-h samples of urine from 53 healthy
      individuals (14 men and 39 women). The urines were collected once a week for 10
      weeks. The data obtained were used as a basis for specimen collection and to gain
      insight into the influence of urine quantities in the diagnosis, screening, and
      monitoring of patients. We found that 24-h urine expressed in output rather than
      concentration units is the most reliable specimen for diagnosis and monitoring
      for most of the analytes studied. On the basis of the ratio between estimated
      within- and between-subject variation, the tests with greatest medical usefulness
      for diagnosis and screening of specific pathologies are those measuring protein
      and sodium. Moreover, the results indicate that urine creatinine may be a poor
      test for diagnosis, monitoring, and screening.

PMID- 7510595
TI  - Diurnal variation of urinary "hCG beta subunit core fragment" production
      evaluated in patients with gynecological neoplasms.

PMID- 7510597
TI  - Effect of a pure nonsteroidal antiestrogen, CDRI-85/287, on implantation-
      associated histological and biochemical changes in the rat uterus.
AB  - The effect of compound CDRI-85/287, a pure, nonsteroidal antiestrogen, on
      implantation-associated changes in rat uterus were studied. Results provide a
      clear correlation between the antideciduogenic action of 85/287 (0.05 mg/kg in
      days 1-5 post-coitum or 2.5 mg/kg on day 1 post-coitum) and the time of its
      administration in relation to the secretion of prenidatory luteal phase estrogen.
      The antiestrogenic nature of the compound is further highlighted by inhibition of
      estradiol-induced increase in vascular permeability. In the present study,
      differences in the pattern of biochemical maturation of the pregnant,
      pseudopregnant and 85/287-treated rat uterus have also been illustrated. As
      compared to the pregnant rat uterus, absence of (the blastocyst and)
      decidualizing tissue in the pseudopregnant rat uterus accounts for the low
      uterine weight, protein, RNA, phospholipids and alkaline phosphatase at the time
      of implantation. Post-coital treatment with 85/287 (2.5 mg/kg, oral) inhibited
      increase in these parameters at the time of implantation. Glycogen levels which
      were lowered in the pregnant rat uterus on days 5 and 6, remain unaltered in the
      pseudopregnant and 85/287-treated rat uteri, suggesting nonutilization of this
      energy substrate. These findings provide sufficient evidence that the
      antiimplantation activity of 85/287 is due to its antiestrogenic property.

PMID- 7510598
TI  - Survival of patients undergoing Nd:YAG laser therapy compared with Nd:YAG laser
      therapy and brachytherapy for malignant airway disease.
AB  - Brachytherapy in combination with Nd:YAG laser therapy may add to the duration of
      survival of the palliative period when compared with laser alone. A retrospective
      study of patients with inoperable squamous cell carcinoma (SCC) was undertaken to
      determine if there was a difference in survival between those patients treated
      with Nd:YAG laser alone and those treated with Nd:YAG laser and brachytherapy.
      Twenty-two patients were treated with brachytherapy for malignant airway disease
      at our institution of which 13 had SCC. All patients had previously received
      treatment with Nd:YAG laser for exophytic disease. Survival was compared with
      those patients treated with Nd:YAG laser alone for SCC involving the airway.
      There was no statistical difference between the two groups with regard to age.
      The duration of survival of patients with SCC of the airway from the first Nd:YAG
      laser treatment was determined. A significant difference between those patients
      treated with Nd:YAG laser alone and those patients treated with combined therapy
      was found (p < 0.001). Brachytherapy may potentiate the duration of survival in
      patients with SCC involving the airway compared to palliation with Nd:YAG laser
      alone.

PMID- 7510596
TI  - The characterization of cytokines in the interface tissue obtained from failed
      cementless total hip arthroplasty with and without femoral osteolysis.
AB  - The histologic, biochemical, and immunohistologic characteristics of the
      interface membranes surrounding the femoral component of failed cementless total
      hip arthroplasty (THA) in patients with (Group I) and without (Group II)
      radiographic evidence of focal endosteal erosion (osteolysis) were studied. Group
      I membranes had more macrophages and small particles of polyethylene debris in
      the membrane, but both groups had similar amounts of metal particles. A greater
      activity level of interleukin-1 (IL-1), tumor necrosis factor (TNF), and
      interleukin-6 (IL-6) was seen in the culture supernatant of the membranes from
      Group I than in that of Group II. Group I membranes also had more cells
      (macrophages, fibroblasts, and endothelial cells) that stained positively with
      anti-IL-6 antibody. These results suggest that IL-6, IL-1, and TNF play a role in
      the focal femoral osteolysis observed in patients with failed cementless hip
      prostheses.

PMID- 7510599
TI  - Prolonged survival after high-dose rate endobronchial radiation for malignant
      airway obstruction.
AB  - STUDY OBJECTIVE: To show that prolonged survival can be observed after high-dose
      rate (HDR) endobronchial brachytherapy as the sole treatment for some selected
      patients presenting with an endobronchial malignant obstruction. PATIENTS: Twenty
      nine patients (group 1) who presented with an endoluminal localized tumor without
      metastatic extension were treated by HDR endobronchial brachytherapy and are
      compared with 22 subjects who presented with extraluminal dissemination and were
      palliatively treated (group 2). TREATMENT PROTOCOL: Treatment consisted of
      sessions of two exposures, delivering 7 Grays at a 10-mm radius from the center
      of the applicator each, and repeated every 15 days, to a maximum of six
      exposures. Endoscopic response and survival are the main criteria of assessment.
      RESULTS: Follow-up bronchoscopies, performed 2 months after the end of the
      procedure, showed tumor regressions: macroscopic complete responses (CR) were
      observed in 21 of 25 patients evaluable in group 1, and 6 of 22 in group 2, with
      histologic CR in 18 and 2 patients, respectively. Median overall survival was not
      reached in group 1 after 23 months of follow-up; it was 5 months for group 2.
      CONCLUSIONS: These results confirm that HDR brachytherapy can be used as a
      monotherapy for carefully selected patients who have small tumors to all
      appearances limited to the bronchial lumen and bronchial wall without adjacent
      parenchymal extension or metastatic disease.

PMID- 7510600
TI  - Doxycycline pleurodesis for pneumothorax in patients with AIDS.
AB  - Since first described in 1984, nontraumatic pneumothoraces in patients with AIDS
      has become more common. When compared with spontaneous pneumothorax in the
      general population, pneumothoraces in patients with AIDS are often complicated by
      prolonged air leaks as well as higher recurrence rates. Chemical pleurodesis has
      an important role in the management of these complications. The most experience
      with chemical pleurodesis uses tetracycline hydrochloride as the sclerosing
      agent; however, this agent is no longer available. Doxycycline has been used in
      pleurodesis of malignant effusions, but its use in managing pneumothoraces is
      limited. We present five patients who have AIDS with a total of seven
      pneumothoraces. Each patient experienced a persistent air leak. Six of the
      pneumothoraces were managed successfully with doxycycline. Although the follow-up
      period was limited, there were no recurrences noted and the only side effect seen
      was chest pain in four which was easily controlled with narcotics. Doxycycline
      sclerotherapy can be used effectively for pleurodesis in the management of
      nontraumatic pneumothorax in the patient with AIDS.

PMID- 7510601
TI  - Single lung transplantation in patients with systemic disease.
AB  - OBJECTIVE: To report functional results and survival in patients undergoing
      single lung transplantation (SLT) for pulmonary involvement associated with
      systemic disease or prior malignancy, criteria traditionally considered
      contraindications to SLT. DESIGN: Case series. SETTING: The University of Texas
      Health Science Center at San Antonio. PATIENTS: Nine patients who have undergone
      SLT for end-stage lung disease: four patients with sarcoidosis; two patients with
      limited scleroderma; and three patients with prior malignancies (two with prior
      lymphoma and bleomycin-induced pulmonary fibrosis and one who received two bone
      marrow transplants for acute lymphocytic leukemia and subsequently developed
      chemotherapy-induced pulmonary fibrosis). MEASUREMENTS: Pulmonary function
      testing, exercise oximetry, quantitative ventilation-perfusion lung scanning.
      Actuarial survival. RESULTS: All patients had marked improvement in pulmonary
      function, exercise oximetry, and quantitative ventilation perfusion to the SLT.
      One patient with scleroderma died 90 days postoperatively from Pseudomonas
      pneumonia with a sepsis syndrome. One patient with sarcoidosis died 150 days
      postoperatively from disseminated aspergillosis. At autopsy, there was no
      evidence of recurrent fibrosis or sarcoidosis in the transplanted lungs in either
      of these two patients. The seven surviving patients have returned to work or
      school and are conducting all activities of daily living without pulmonary
      disability. The 1- and 2-year actuarial survival rates in these nine patients is
      68.6 percent as compared with the 1- and 2-year actuarial survival rates of 66.3
      percent and 55.8 percent in the remainder of our SLT group as a whole (n = 49).
      Despite pharmacologic immunosuppression, there is no evidence of recurrent
      malignancy in the 3 patients with prior malignancies. CONCLUSIONS: We conclude
      that carefully selected patients with end-stage lung involvement related to
      systemic disease or chemotherapy-induced fibrosis may benefit from SLT.

PMID- 7510602
TI  - Use of the flow-volume loop in the diagnosis of bronchial stenosis after single
      lung transplantation.
AB  - Bronchial complications, including stricture, stenosis, and/or anastomotic
      dehiscence, are a major cause of morbidity following single lung transplantation.
      This report describes a 19-year-old man with a diagnosis of end-stage pulmonary
      fibrosis secondary to prior chemotherapy for non-Hodgkins lymphoma who underwent
      single lung transplantation. The immunosuppressive regimen included cyclosporine,
      azathioprine, and methylprednisolone sodium succinate (Solu-Medrol) intravenously
      for six doses during the first 3 days postoperatively followed by oral
      prednisone. Sixteen weeks following transplantation, the patient complained of
      dyspnea. Spirometry revealed a decrease in FEF25-75 and the flow-volume curve
      demonstrated a bioconcave appearance. The flow-volume loop showed a relatively
      high initial flow phase occurring over the first 2 to 3 s followed by a low-flow
      phase. The expiratory phase also showed the same characteristics. Bronchoscopy
      revealed 75 percent stenosis of the bronchial lumen to the transplanted lung. A
      transbronchial biopsy specimen obtained at that time was consistent with acute
      rejection. The patient was treated with a methylprednisolone bolus. A repeated
      bronchoscopy showed the persistence of stenosis distal to the anastomosis. The
      patient underwent several bronchoplastic balloon dilatations without complete
      resolution of the stenosis and a stainless steel mesh stent was placed. Repeated
      spirometry showed marked improvement of the FEF25-75 and normalization of the
      flow-volume loop. We conclude that the flow-volume loop curve is a noninvasive
      procedure that may help monitor the patency of the bronchial anastomoses
      following single lung transplantation.

PMID- 7510603
TI  - Lipopolysaccharide-binding protein and CD14 in the lipopolysaccharide-dependent
      activation of cells.

PMID- 7510604
TI  - Endotoxin, endotoxin-binding protein, and soluble CD14 are present in
      bronchoalveolar lavage fluid of patients with adult respiratory distress
      syndrome.

PMID- 7510606
TI  - Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with
      inflammatory bowel disease (IBD). Relation to disease pattern and disease
      activity.
AB  - Anti-neutrophil cytoplasmic antibodies producing a perinuclear fluorescence
      pattern on ethanol-fixed granulocytes (p-ANCA) were found in 33 of 67 patients
      (49%) with ulcerative colitis (UC) but also in 14 of 35 patients (40%) with
      Crohn's disease (CD). In the latter condition p-ANCA were equally present in
      subgroups with colonic, ileocolonic, or ileal involvement only. Titers of p-ANCA
      were higher in patients with UC compared to CD patients, in particular when
      comparing patients with active disease. In contrast to findings in CD, patients
      with active UC had higher titers of p-ANCA than patients with inactive UC.
      Although p-ANCA were incidentally directed to lactoferrin, both in UC and CD, and
      to proteinase-3 and myeloperoxidase in UC only, the antigenic nature of p-ANCA
      could not be identified in most of the cases. We conclude that, within the
      spectrum of inflammatory bowel disease, the presence of p-ANCA is not specific
      for UC. When titers of p-ANCA are taken into account, the presence of high
      titered p-ANCA, however, suggests active UC.

PMID- 7510607
TI  - Somatostatin effectively prevents ethanol- and NSAID-induced gastric mucosal
      damage in rats.
AB  - The interrelationship between somatostatin and its synthetic analog, sandostatin,
      with neuropeptides and inflammatory mediators, as well as their protection of
      gastric mucosal damage, were tested in rats. Rats were treated intragastrically
      with 1.0 ml of 96% ethanol with or without intravenous or intraperitoneal
      coadministration of somatostatin (1.0 microM/kg). Mucosal damage was also induced
      by the administration of either indomethacin (30 mg/kg subcutaneously) with or
      without intravenous sandostatin (10 micrograms/rat), given 30 min prior to damage
      induction. Somatostatin levels in ethanol-damaged gastric mucosa were
      significantly lower than in control rats. Substance P and vasoactive intestinal
      peptide (VIP) levels were significantly higher in the damaged mucosa in rats
      treated with ethanol, as was the mucosal generation of leukotriene B4 (LTB4) and
      cysteinyl-containing leukotrienes. The coadministration of somatostatin with
      ethanol significantly reduced gastric mucosal injury induced by ethanol alone.
      The protection of the mucosa was accompanied by reduction of mucosal substance P
      and VIP levels, as well as the generation of leukotrienes, an effect that was
      reversed by intraperitoneal or intravenous coadministration of somatostatin
      antagonist, cyclo-(7-aminoheptanoyl-PH-E-D-Trp-Lys-THR), 1.0 microM/100 g, with
      somatostatin (1.0 microM/kg) and ethanol. When given by itself somatostatin
      significantly reduced mucosal leukotriene generation compared with their
      generation in saline-treated rats. Sandostatin completely abolished gastric
      mucosal damage induced by indomethacin administration. In rats treated with
      somatostatin and indomethacin, this effect was accompanied by reduction of
      mucosal leukotriene generation. Administration of sandostatin to pylorus-ligated
      rats significantly reduced gastric acid output.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510605
TI  - Antitumor, anti-inflammatory and analgesic property of embelin, a plant product.
AB  - Embelin, a plant-based benzoquinone derivative, has been found to exhibit
      significant antitumor activity in methylcholanthrene-induced fibrosarcoma in
      albino rats besides enhancing their survival time. The drug also has an
      appreciable action on pain and inflammation. The changes in DNA, RNA and protein
      levels in various organs in the tumor-bearing control and the drug-treated
      animals were also studied.

PMID- 7510608
TI  - [Autologous blood donation, acetylsalicylic acid and risk of bleeding after
      coronary bypass operation].

PMID- 7510610
TI  - Acarbose. An update of its pharmacology and therapeutic use in diabetes mellitus.
AB  - Acarbose delays digestion of complex carbohydrates and disaccharides to
      absorbable monosaccharides, by reversibly inhibiting alpha-glucosidases within
      the intestinal brush border, thereby attenuating postprandial blood glucose
      peaks. Clinical trials have demonstrated that acarbose generally improves
      glycaemic control in patients with non-insulin-dependent diabetes mellitus
      (NIDDM) managed with diet alone, or with other antidiabetic therapy, as evidenced
      by decreased postprandial plasma glucose and glycosylated haemoglobin levels. It
      does not appear to directly alter insulin resistance, but may lower postprandial
      plasma insulin levels. Fasting plasma glucose, triglyceride and/or cholesterol
      levels may also be decreased. Acarbose also improved metabolic control in
      patients with insulin-dependent diabetes mellitus (IDDM), frequently decreasing
      insulin requirements, although further studies are required in this indication.
      Improved metabolic control appears to delay or prevent long term vascular
      complications of diabetes, and indeed, acarbose appeared to inhibit development
      of such complications in preliminary animal studies, but this finding requires
      confirmation in clinical studies. While acarbose seldom causes systemic adverse
      effects, it is associated with a high incidence of gastrointestinal disturbances
      such as flatulence, abdominal distension, borborygmus and diarrhoea, caused by
      fermentation of unabsorbed carbohydrates. However, these symptoms tend to subside
      with continued treatment and adherence to an appropriate diet. Thus, acarbose
      appears to be a worthwhile adjunctive therapeutic option for patients with NIDDM
      inadequately managed by diet alone, or with pharmacological therapy, and possibly
      also for patients with IDDM. However, further long term efficacy and tolerability
      data are required, particularly in the latter indication.

PMID- 7510611
TI  - Cetirizine. A reappraisal of its pharmacological properties and therapeutic use
      in selected allergic disorders.
AB  - Cetirizine, the carboxylated metabolite of hydroxyzine, is a specific and long
      acting histamine H1-receptor antagonist. It has marked antiallergic properties
      and inhibits eosinophil chemotaxis during the allergic response. Clinical trial
      results indicate that cetirizine is an effective and well tolerated treatment for
      seasonal/perennial allergic rhinitis and chronic idiopathic urticaria in adults,
      and for seasonal/perennial allergic rhinitis in children. Cetirizine 10 mg/day
      appears to be as effective as conventional dosages of other established
      antihistamines such as astemizole, hydroxyzine, ketotifen, loratadine or
      terfenadine in relieving symptoms of these disorders, and is associated with a
      significantly lower incidence of sedation than hydroxyzine. However, when
      sedation was subjectively assessed, cetirizine appeared to be more sedating than
      placebo, loratadine or terfenadine in some clinical trials. This difference was
      not observed in several other double-blind studies. In contrast, when assessed
      objectively in pharmacodynamic comparisons, cetirizine was rarely more sedating
      than placebo or other second generation histamine H1-receptor antagonists.
      Cetirizine may also have a role in the treatment of certain forms of physical
      urticaria, atopic dermatitis and reactions to mosquito bites. In addition, it is
      being studied for the treatment of allergic asthma in adults and children. The
      pharmacokinetic profile and predominantly renal excretion of cetirizine suggest
      that this agent may have a reduced potential for adverse drug interactions
      involving hepatic enzyme systems compared with other histamine H1-receptor
      antagonists which are extensively metabolised. Thus, cetirizine, with its rapid
      onset and long duration of action, appears to provide a useful alternative to the
      antihistamine agents in clinical use.

PMID- 7510609
TI  - Place of newer antiepileptic drugs in the treatment of epilepsy.
AB  - There are several new antiepileptic drugs undergoing extensive clinical
      investigation. Five new drugs--vigabatrin, lamotrigine, gabapentin, felbamate and
      oxcarbazepine--appear to be the most widely tested and promising agents.
      Vigabatrin is most effective in drug-resistant partial epilepsy. Vigabatrin is
      also effective in infantile spasms, but seems to have negative effects on
      myoclonic epilepsies and absence seizures. Lamotrigine and felbamate seem to be
      effective in partial epilepsy and in Lennox-Gastaut syndrome. In addition,
      lamotrigine and felbamate seem to have efficacy in idiopathic generalised
      epilepsies. Oxcarbazepine appears to be equally as effective as carbamazepine,
      but less toxic. Gabapentin has few adverse effects and has efficacy in some
      patients with drug-resistant partial epilepsy. Some of the new antiepileptic
      drugs modify excitatory or inhibitory amino acid transmission, but some of them
      may employ new, still unknown mechanisms of action. Depending on the mechanism of
      action, the therapeutic effectiveness of the antiepileptic drugs may differ in
      specific epileptic syndromes. Future antiepileptic drugs may thus give us the
      possibility to design rational polypharmacy for individual patients by combining
      agents with different spectra of effectiveness. Considering the goal of good
      tolerability in the development of the new antiepileptic drugs, polypharmacy with
      these agents is not expected to increase adverse effects significantly.

PMID- 7510612
TI  - Anti-HIV vaccines. Current status and future developments.

PMID- 7510613
TI  - New uses for calcium channel blockers. Therapeutic implications.
AB  - Calcium antagonists block calcium entry into cells, resulting in relaxation of
      smooth muscle and limitation of the cytotoxic effects of ischaemia in various
      organ systems. They are most frequently used for clinical conditions requiring
      vasodilatation, i.e. hypertension and Raynaud's phenomenon, and this also
      suggests that the most common adverse effect of these drugs for noncardiovascular
      indications is an unwanted decline in blood pressure. Other uses include
      treatment of supraventricular arrhythmias and angina. There is some evidence that
      these drugs retard the development of atherosclerosis. Calcium channel blockers
      also improve renal reperfusion and may reduce renal insufficiency due to various
      nephrotoxins, and are particularly useful in renal transplantation for protection
      against cyclosporin toxicity and post-transplant acute tubular necrosis. These
      drugs are also useful in pregnancy-induced hypertension and unwanted uterine
      contraction. Affective disorders and malignancies may be other conditions which
      benefit from calcium antagonist therapy. Calcium antagonists, in particular
      nimodipine which is most selective for the cerebral vasculature, have been
      approved for treating vasospasm after subarachnoid haemorrhage. They are probably
      also effective for treatment of migraine. Calcium channel blockers may be
      effective for treating acute cerebral infarction, but results of clinical trials
      to date have been equivocal, largely because it has been difficult to recruit
      patients within the short interval after the onset of stroke when these drugs
      would be most effective, and because of the unwanted hypotensive effect of high
      doses.

PMID- 7510614
TI  - Safety profile of ranitidine. A review.
AB  - Ranitidine has been used for the treatment of millions of patients during the
      past 10 years. A small proportion of patients have developed a reaction to the
      drug shortly after the start of treatment, usually as a result of 'individual
      idiosyncrasy'. Reactions during continuous, long term treatment with ranitidine
      are uncommon, so that maintenance treatment of the chronic peptic diseases with
      ranitidine for more than 10 years has not been associated with significant
      iatrogenic disease.

PMID- 7510615
TI  - Potassium supplements and potassium-sparing diuretics. A review and guide to
      appropriate use.
AB  - Epidemiological and clinical studies suggest that low dietary potassium intake
      may have an important role in determining the development of diseases such as
      hypertension, and perhaps even stomach cancer, and that increased potassium
      intake may have beneficial effects in several other conditions. Dietary
      adjustment or active potassium supplementation has been suggested as a natural,
      less costly and safe method of increasing potassium levels, although active
      supplementation with tablets or solutions is not recommended in healthy people
      with normal serum potassium levels. However, increasing dietary potassium intake
      in the elderly and in patients with renal impairment must be considered with
      caution. Diuretics have a long established role in the management of hypertension
      and heart failure. There is no convincing evidence to suggest that the small
      reduction in plasma potassium levels associated with low dose thiazide and loop
      diuretic therapy needs to be routinely prevented by the use of potassium-sparing
      drugs. In non-digitalised patients little association has been found between mild
      diuretic-induced hypokalaemia and arrhythmias. Thus, the routine prophylactic use
      of potassium-sparing diuretics in combination with non-potassium-retaining
      diuretics for the treatment of hypertension and oedematous states is not
      justified. Based on current evidence, treating all patients whose serum potassium
      level decreases below 3 mmol/L is recommended, although for certain patients at
      particular risk of hypokalaemia, levels may need to be maintained above 3.5
      mmol/L. In overt hypokalaemia, several therapeutic options are available to the
      clinician. These include increased consumption of potassium-rich foods, the use
      of salt substitutes, medicinal potassium supplementation or distal tubular
      (potassium-sparing) diuretics.

PMID- 7510616
TI  - Over-the-counter histamine H2-receptor antagonists. How will they affect the
      treatment of acid-related diseases?

PMID- 7510618
TI  - Leukotrienes as a target in asthma therapy.
AB  - Asthma is a chronic inflammatory condition characterised by bronchial hyper
      responsiveness and reversible airways obstruction. Research has demonstrated that
      these effects are mediated by a wide range of compounds. In the last decade
      leukotrienes have been identified as products of arachidonic acid metabolism.
      Their effects mimic the pathological changes seen in asthma both in vitro and in
      vivo. Further research has demonstrated increased production of leukotrienes both
      during episodes of asthma and in patients with stable asthma. The demonstration
      that leukotrienes have proinflammatory biological properties relevant to the
      pathogenesis of asthma has stimulated the development of many potential
      therapeutic compounds to block these actions. Early studies in laboratory-induced
      asthma in human volunteers have shown the efficacy of some of these compounds.
      They have been shown to attenuate the bronchoconstriction caused by allergen
      challenge, exercise, aspirin and exposure to cold air. Most encouraging of all
      have been recent placebo-controlled studies in clinical asthma where significant
      improvements in terms of spirometry, symptoms and beta 2-agonist use have been
      demonstrated. Leukotriene receptor antagonists and synthesis inhibitors are the
      first mediator antagonists to have been shown to be effective in treating
      clinical asthma and as such represent one of the most interesting new classes of
      antiasthma drugs in development at present.

PMID- 7510617
TI  - Cisapride. An updated review of its pharmacology and therapeutic efficacy as a
      prokinetic agent in gastrointestinal motility disorders.
AB  - Cisapride is an orally administered prokinetic agent which facilitates or
      restores motility throughout the length of the gastrointestinal tract. It is a
      substituted piperidinyl benzamide, chemically related to metoclopramide, but
      unlike metoclopramide, cisapride is largely devoid of central depressant or
      antidopaminergic effects. In placebo-controlled trials, cisapride improved
      healing rates and symptoms in both adults and children with reflux oesophagitis.
      Maintenance therapy with cisapride at half the healing dose is effective in
      reducing the incidence of relapse. Symptoms are also alleviated in patients with
      functional dyspepsia, and gastric emptying and symptoms are improved in most
      patients with gastroparesis, an effect which is sustained during long term
      administration. However, the efficacy of cisapride in end-stage gastroparesis
      remains less clear. Cisapride increases stool frequency in patients with chronic
      constipation, and limited data suggest that the drug may also be beneficial in
      treating chronic intestinal pseudo-obstruction and irritable bowel syndrome.
      Cisapride demonstrated efficacy comparable with or superior to that of
      metoclopramide, and was at least as effective as cimetidine and ranitidine in
      patients with reflux disease. In patients with functional dyspepsia, cisapride
      has shown at least equal efficacy to domperidone, metoclopramide and ranitidine,
      and superior efficacy to cimetidine in the small comparative trials conducted to
      date. Adverse effects in patients receiving cisapride are generally transient and
      mild, with abdominal cramping, borborygmi, diarrhoea or loose stools most
      frequently reported. Central nervous system adverse effects are rare. Thus, with
      its favourable tolerability profile and demonstrated efficacy in a variety of
      gastrointestinal motility disorders, the position of cisapride as a valuable
      agent in the management of patients with gastrointestinal motility disorders is
      strengthening. However, larger well-controlled comparative trials of the drug
      with other agents are necessary before the relative position of cisapride in
      therapy can be categorically defined.

PMID- 7510622
TI  - Benign prostatic hyperplasia. Current pharmacological treatment.
AB  - During the past decades, pharmacological treatment of symptomatic benign
      prostatic hyperplasia (BPH) has become a fairly established modality. Approaches
      include blockade of alpha-adrenoreceptors and suppression of androgens. Patients
      eligible for drug treatment are those with mild to moderate symptoms of BPH and
      no strong indications for surgery. alpha-Receptor blockers generally improve
      urinary symptoms and peak urinary flow rates 2 to 4 weeks after introduction of
      therapy. Because of minor adverse effects, selective alpha 1-blockers are
      preferred over nonselective drugs. Prazosin, terazosin and alfuzosin are
      extensively studied and widely used in BPH treatment. Terazosin might be
      preferred to prazosin and alfuzosin because it can be administered once daily,
      but a disadvantage is higher cost. Doxazosin and tamsulosin (amsulosin; YM 617)
      are drugs currently under clinical investigation in the treatment of BPH.
      Antiandrogen therapy induces reduction in prostate volume and relief in symptoms
      of bladder outlet obstruction. However, the only drug which seems to be of major
      interest in BPH treatment is finasteride. Other drugs [gonadotrophin-releasing
      hormone (GnRH) agonists, progestogens and flutamide] are associated with frequent
      and sometimes severe adverse effects, such as impotence, flushing and loss of
      libido. Finasteride has fewer adverse effects and is well tolerated, but needs to
      be administered for at least 6 to 12 months to obtain maximum effect. Future
      approaches in medical treatment of BPH might be combination therapy of alpha 1
      blockers and finasteride.

PMID- 7510621
TI  - Torsade de pointes. Mechanisms and management.
AB  - Torsade de pointes is a polymorphic ventricular tachycardia showing a peculiar
      electrocardiographic pattern characterised by a continuous twisting in QRS axis
      around an imaginary baseline. An abnormally prolonged QT interval is actually
      associated with torsade de pointes and it is constantly observed in the sinus
      beats preceding the onset of the arrhythmic event. Prolongation of ventricular
      repolarisation associated with the development of torsade de pointes can be
      observed in many clinical conditions, commonly referred to as prolonged QT
      syndromes, which can be divided into two major groups: (a) idiopathic long QT
      syndrome (LQTS), which include the Jervell-Lange-Nielsen and the Romano-Ward
      syndromes; and (b) acquired prolonged QT syndromes, which are largely iatrogenic
      and may follow treatment with antiarrhythmic drugs, tricyclic antidepressants,
      phenothiazines or macrolide antibiotics, and may be associated with metabolic
      disturbances (hypokalaemia, hypocalcaemia and hypomagnesaemia). Clinical studies
      have provided criteria for the definition and guidelines for the management of
      torsade de pointes, while the electrophysiological mechanisms responsible for its
      onset are still unclear. Two pathogenetic hypotheses have been proposed to
      account for the electrophysiological mechanisms underlying the condition: (a) re
      entry due to a dispersion of refractory periods; and (b) triggered activity
      initiated by either early or delayed after-depolarisations. Both mechanisms are
      supported by clinical and experimental observations but a conclusive answer is
      not yet available.

PMID- 7510623
TI  - Treatment recommendations for osteosarcoma and adult soft tissue sarcomas.
AB  - During the past 20 years, dramatic improvements have been obtained in the
      treatment of localised osteosarcoma of the extremities, both in the rates of
      disease-free survival and in quality of life. Twenty years ago 80 to 90% of the
      patients died, in spite of mutilating surgery, but now about 75% survive and
      avoid the necessity of amputation. This is due to the introduction of very
      effective combined treatments, mostly also using preoperative chemotherapy. One
      of the major issues is that of intensive preoperative chemotherapy, which
      improves both limb salvage and survival. A multidisciplinary approach is
      necessary to obtain good results. When the role of adjuvant or neoadjuvant
      chemotherapy is not accurately defined for soft tissue sarcomas, particular
      emphasis is given to the staging of the diseases and to the important role of
      local treatment in the survival of these patients. A combination of radiation
      therapy and surgery is strongly recommended.

PMID- 7510626
TI  - Neural network analysis of the P300 event-related potential in multiple
      sclerosis.
AB  - Neural network analysis is sensitive to subtle changes in patterns of data. We
      hypothesized that a disease process which can cause impairment of cortical
      function such as multiple sclerosis (MS) would affect the P300 cognitive evoked
      potential (P300) in a manner detectable by a feedforward backpropagation neural
      network. Such a network was trained using a learning data set consisting of 101
      P300 wave forms (from 26 MS patients and 26 normal controls). The network was
      then used to classify a randomly selected test data set of 20 studies (2 studies
      each of 5 MS patients and 5 controls) to which it had not been previously
      exposed, with an average accuracy (MS = abnormal, control = normal) of 81% for a
      single midline electrode, increasing to 90% using 3 midline electrodes in a jury
      system. Neural network analysis can be of help in distinguishing normal (control)
      P300 from abnormal (MS) P300.

PMID- 7510625
TI  - A developmental study of visual ERP distributions during spatial and phonetic
      processing.
AB  - Ten adults (mean age 19.5 years; S.D. = 1.65) and 10 children (12.2 years; S.D. =
      1.28) participated in a choice reaction time study of event-related potential
      (ERP) correlates of pattern and phonological discriminations of letters. In the
      form condition, the subjects responded discriminately to letters that did (e.g.,
      b, p) and did not (e.g., f, h) have an enclosed area. Likewise, the subjects
      responded to letters that did and did not rhyme with "e" in the rhyme task. For
      both groups, the two late positivities (P600 and P3) were significantly later in
      the rhyme ERPs than the form as were the RTs associated with the tasks.
      Distribution and group differences were most notable for the positivity at 380
      msec. The P380 distribution did not vary between the conditions for the adults,
      but there was a more negative distribution in the rhyme condition compared to the
      form at fronto-central sites for the children. The topographic differences
      between the form and rhyme tasks at 380 msec were consistent with the involvement
      of auditory areas in the rhyme task. Generally, however, the children's and
      adults' wave forms were similar in terms of morphology, peak latency and
      distribution.

PMID- 7510627
TI  - Methodological considerations in measurement of the P300 component of the
      auditory oddball ERP in schizophrenia.
AB  - Twenty-three schizophrenic patients and 26 age-matched control subjects were
      studied using the P300 recorded during the auditory oddball task, with counting.
      Our aim was to assess the most suitable method of measurement and analysis of
      P300 amplitude and latency for use in clinical studies of schizophrenia. The
      effect of high-pass filtering, peak definition method and recording electrode
      site were all investigated. We have developed a technique, based on a least-mean
      squares approximation to data, which seems particularly well suited to dealing
      with multi-peak P300 complexes. We have also investigated the spectral
      composition of the P300 and have found some evidence to support a proposed 2
      frequency model of the P300 complex.

PMID- 7510624
TI  - Gallopamil. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic potential in ischaemic heart disease.
AB  - Gallopamil is a methoxy derivative of verapamil. As is typical of the
      phenylalkylamine class of calcium antagonists, it acts on the vascular system,
      and on the heart and its nodal structures. In the treatment of stable angina
      pectoris, gallopamil is at least as effective as nifedipine and diltiazem, though
      apparently better tolerated than nifedipine. Typical of calcium antagonists there
      is little or no tolerance to the antiischaemic effects of gallopamil. Preliminary
      studies indicate that gallopamil, like other calcium antagonists, has
      cardioprotective potential. However, further investigation is required to explore
      the clinical relevance of the improved myocardial regional perfusion and free
      fatty acid utilisation in reversibly ischaemic regions, and the potential of
      delayed ischaemia during angioplasty that is observed during gallopamil
      administration. Gallopamil is well tolerated, exhibiting a low propensity for
      causing cardiovascular and gastrointestinal adverse effects, thus making it a
      suitable alternative to other calcium antagonists for the treatment of patients
      with ischaemic heart disease.

PMID- 7510628
TI  - Positive shifts of event-related potentials: a state of cortical disfacilitation
      as reflected by the startle reflex probe.
AB  - Cortical positivity as measured by slow event-related potentials is assumed to
      represent a decreased excitability of cortical networks and suppression of their
      behavioral-cognitive output. The blink reflex probe is a commonly used defensive
      electromyographic response whose amplitude was shown to be modulated by emotional
      and attentional orientation. It was used here as an indicator of cortico
      subcortical excitation. In study 1, 33 healthy subjects took part in a continuous
      performance test (CPT). Event-related potentials were recorded from 15 standard
      scalp locations. Acoustic startling noise bursts were delivered during conditions
      that required either performance of prepared motor responses (Go), inhibition of
      prepared motor responses (NoGo), or had no motor significance (Irrelevant
      condition). During the NoGo condition, EEG surface potentials showed a widespread
      P300-like positivity with a central maximum. Startle responses were inhibited
      during the NoGo condition as compared to the Irrelevant condition. In study 2 (21
      subjects) the same format was used, except that the startle reflex was elicited
      visually. Startle reflexes again showed smaller magnitude during the NoGo
      condition, which evoked larger positivity at central sites in comparison to the
      Irrelevant condition. The relationship between positivity in the EEG and
      inhibited startle responses is in line with the hypothesis that positive EEG
      shifts reflect a state of cortical disfacilitation.

PMID- 7510620
TI  - Methotrexate in rheumatoid arthritis. An update.
AB  - Methotrexate has been approved for the treatment of refractory rheumatoid
      arthritis by several regulatory agencies, including the Food and Drug
      Administration. The tendency is now to prescribe it at earlier stages of the
      disease. Methotrexate is a well known antifolate. Its exact mechanism of action
      in rheumatoid arthritis remains uncertain. The polyglutamated derivatives of
      methotrexate are potent inhibitors of various enzymes, including dihydrofolate
      reductase and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase.
      Inhibitory effects on cytokines, particularly interleukin-1, and on arachidonic
      acid metabolism, as well as effects on proteolytic enzymes, have been reported.
      Some of them may be linked to the antifolate properties of methotrexate. Overall,
      the drug appears to act in rheumatoid arthritis as an anti-inflammatory agent
      with subtle immunomodulating properties. Direct inhibitory effects on rapidly
      proliferating cells in the synovium have also been suggested. Methotrexate is
      usually given orally. Marked interindividual variation in its bioavailability has
      been found. Food intake has no significant effect on the pharmacokinetics of oral
      methotrexate. Methotrexate undergoes significant metabolism. The functionally
      important metabolites are the polyglutamated derivatives of methotrexate, which
      are selectively retained in the cells. Less than 10% of a dose of methotrexate is
      oxidised to 7-hydroxy-methotrexate, irrespective of the route of administration.
      This metabolite is extensively (91 to 93%) bound to plasma proteins, in contrast
      to the parent drug (35 to 50% bound). Methotrexate is mainly excreted by the
      kidneys. It undergoes tubular secretion and may thereby compete with various
      organic acid compounds. Early placebo-controlled trials demonstrated that weekly
      low dosage methotrexate produced early symptomatic improvement in most rheumatoid
      arthritis patients. Two meta-analyses showed that methotrexate is among the most
      efficacious of slow-acting antirheumatic agents, together with parenteral gold
      (sodium aurothiomalate), penicillamine and sulfasalazine. Furthermore, in the
      short term context of clinical trials, methotrexate has one of the best
      efficacy/toxicity ratios. There is little evidence that methotrexate, or any
      available slow-acting antirheumatic agent, is a true disease-modifying drug.
      However, the probability that a patient will continue methotrexate therapy over
      time appears quite favourable compared with any other slow-acting antirheumatic
      drug. Combination therapy with slow-acting drugs has been advised for the
      management of rheumatoid arthritis, but the evidence currently available does not
      support general use of combination therapy including methotrexate. Almost all
      investigations indicated that toxic effects, rather than lack of response, were
      the major reason for discontinuing methotrexate therapy.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7510629
TI  - Intrasubject reliability and validity of somatosensory source localization using
      a large array biomagnetometer.
AB  - Neuromagnetic fields were evoked by tactile stimuli and detected with a multi
      channel biomagnetometer through 72 independent repetitive measurements on a
      single subject. Each measurement consisted of a somatosensory evoked response (N
      = 256 stimuli) using a single probe placement. These fields were then analyzed
      for source localization using an equivalent current dipole model and demonstrated
      highly reliable localizations. The 3 major neuromagnetic somatosensory response
      components peaking at 35, 65 and 110 msec all localized to the same area of
      cortex. The relative contributions of intrinsic brain activity, habituation,
      probe placement, and choice of fiduciary points for headframe determination were
      quantified. Intrinsic factors were found to constitute the major source of inter
      measurement error. Sources localized by magnetic source imaging (MSI) appeared
      valid relative to neuroanatomical estimation of the central fissure on MRI. Non
      invasive presurgical biomagnetic localization of somatosensory cortex produces
      reliable and valid functional localizations which can be of potential value in
      risk assessment and may provide a useful guide for invasive functional mapping.

PMID- 7510619
TI  - Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties
      and therapeutic efficacy.
AB  - Aciclovir (acyclovir) is a nucleoside analogue with antiviral activity in vitro
      against the herpes simplex viruses (HSV), varicella zoster virus (VZV), Epstein
      Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6). Topical,
      oral or intravenous aciclovir is well established in the treatment of ophthalmic,
      mucocutaneous and other HSV infections, with intravenous aciclovir the accepted
      treatment of choice in herpes simplex encephalitis. The efficacy of aciclovir is
      increased with early (preferably during the prodromal period) initiation of
      treatment but, despite significant clinical benefit, viral latency is not
      eradicated, and pretreatment frequencies of recurrence usually continue after
      episodic acute treatment is completed. Intravenous administration has also shown
      benefit in the treatment of severe complications of HSV infection in pregnancy,
      and neonatal HSV infections. Recurrence of HSV has been completely prevented or
      significantly reduced during suppressive therapy with oral aciclovir in
      immunocompetent patients. Use of oral aciclovir is effective but controversial in
      the treatment of otherwise healthy individuals with varicella (chickenpox), and
      in some countries it has been recommended for use only in cases which may be
      potentially severe. The development of rash and pain associated with herpes
      zoster (shingles) is attenuated with oral or intravenous aciclovir therapy,
      ocular involvement is prevented, and post-herpetic neuralgia appears to be
      decreased. Similarly, in a few patients with zoster ophthalmicus, oral aciclovir
      has reduced the frequency and severity of long term ocular complications and post
      herpetic neuralgia, and herpes zoster oticus is improved with intravenous
      aciclovir. Oral aciclovir has prevented recurrence of HSV genital or orofacial
      infections during suppressive therapy in > 70% of immunocompetent patients in
      most clinical trials. Suppression of latent HSV, VZV and CMV infections has been
      achieved in many immunocompromised patients receiving the oral or intravenous
      formulations. Aciclovir also appears to offer partial protection from invasive
      CMV disease in CMV-seropositive bone marrow transplant recipients. The few
      comparative trials published have shown aciclovir to be at least as effective as
      other investigated antivirals in the treatment of HSV infections in
      immunocompetent patients, and more effective than inosine pranobex in the
      prophylaxis of genital herpes. Similarly, in isolated clinical trials, oral
      aciclovir appears as effective as topical idoxuridine and oral brivudine in some
      parameters in immunocompetent patients with VZV infections, and the intravenous
      formulation appears at least as effective as oral brivudine and intravenous
      vidarabine in treating these infections in immunocompromised patients.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7510631
TI  - Reversible myoclonic encephalopathy revealing the AIDS-dementia complex.
AB  - A 40-year-old HIV-positive right handed homosexual man was admitted for
      progressive mental deterioration coexisting with permanent segmental middle
      amplitude arrhythmic, asynchronous and asymmetrical myoclonic jerks. EEG showed
      fronto-central bursts of rhythmic triphasic 1.5-2 Hz sharp waves similar to the
      characteristic periodic pattern of Jakob-Creutzfeldt disease. Biological
      procedures were negative, thus eliminating a metabolic encephalopathy. Dramatic
      neurological improvement occurred shortly after initiation of i.v. and then oral
      zidovudine which produced perfect EEG normalisation. This unusual electroclinical
      presentation of the AIDS-dementia complex underlines the fact that this affection
      may present a diagnostic challenge, particularly in individuals in whom HIV
      infection is unknown.

PMID- 7510630
TI  - Slow magnetic flux from human frontal cortex.
AB  - Slow magnetic fields concurrent with two successive contingent negative
      variations (CNVs) were elicited in 8 subjects during visual recognition tasks
      involving pattern versus place discrimination. All stimuli were presented as a
      rectangular array of lights with various patterns of 6 lights at the center and,
      simultaneously, with places indicated by missing lights at the periphery. One of
      two possible stimuli (warning) started each trial, indicating whether pattern or
      place recognition should be performed on the following two stimuli. The purposes
      of the experiment were to localize the sources of the slow magnetic fields
      equivalent to the CNVs and to address the issue of regional specialization of
      prefrontal cortical function. Results indicated that the equivalent current
      dipoles (ECDs) found as solutions for the measured slow fields were indeed
      localized in the prefrontal cortex of each hemisphere. Also, in the right
      hemisphere, the source location of the CNVs was dependent on task, which
      supported the hypothesis of specialization of prefrontal function. The place
      recognition task was associated with more anterior and inferior CNV sources than
      the pattern recognition task. Finally, it was observed that ECDs for the warning
      period CNVs were indistinguishable from those for the test period of the tasks.

PMID- 7510632
TI  - Lower brain-stem origin of the median nerve N18 potential.
AB  - A patient undergoing intraoperative median nerve somatosensory evoked potential
      (MSEP) and brain-stem auditory evoked response (BAER) monitoring showed changes
      during basilar artery aneurysm clipping. There was loss of the BAER wave V, with
      preservation of waves I and III. Simultaneously, there also was loss of the MSEP
      N20 potential, with preservation of the N18, N13 and Erb's point potentials. The
      patient died and autopsy showed an infarct involving the whole rostro-caudal
      extent of the pontine tegmentum. This combination of electrophysiologic and
      pathologic findings may help answer questions regarding the exact generators of
      different MSEP potentials. In particular, it implies that medullary structures
      can generate the N18 potential.

PMID- 7510633
TI  - Cortical reactivity in progressive myoclonus epilepsy.
AB  - We studied 4 patients with progressive myoclonus epilepsy (Unverricht-Lundborg
      disease; ULD). Somatosensory evoked fields (SEFs), auditory evoked fields (AEFs),
      and spontaneous activity over the somatomotor cortex were recorded with a 24
      channel SQUID gradiometer. All patients had "giant" 20-45 msec median nerve SEFs
      at the first somatomotor cortex, with 2-6 times larger amplitudes than the
      healthy control subjects. Later deflections were not similarly enhanced. The
      dependence of SEF amplitudes on interstimulus interval (0.2-4 sec) and on
      successive ulnar-median nerve stimulation (stimulus interval 40 msec) was
      comparable to that in controls. Cortical AEFs were attenuated and delayed. In 3
      patients, the spontaneous activity consisted of 6-8 Hz mu rhythm, which
      originated within 2 cm from the sources of SEFs and was abolished by clenching of
      the contralateral fist. Control subjects had major spectral peaks around 10 and
      20 Hz. The SEF amplitudes and the strength of the 6-10 Hz mu correlated strongly,
      suggesting that some components of evoked and spontaneous activity obtain
      contributions from overlapping neuronal populations. The results imply that ULD
      is associated with thalamo-cortical hyperreactivity in the sensorimotor but not
      in the auditory system.

PMID- 7510634
TI  - Activation of intestinal CFTR Cl- channel by heat-stable enterotoxin and guanylin
      via cAMP-dependent protein kinase.
AB  - Heat-stable enterotoxins (STa) produced by pathogenic bacteria induce profound
      salt and water secretion in the gut, leading to diarrhea. Recently, guanylin, an
      endogenous peptide with properties similar to STa, was identified. While STa and
      guanylin bind to the same receptor guanylyl cyclase and raise cell cGMP, the
      signaling mechanism distal to cGMP remains controversial. Here we show that STa,
      guanylin and cGMP each activate intestinal Cl- secretion, and that this is
      abolished by inhibitors of cAMP-dependent protein kinase (PKA), suggesting that
      PKA is a major mediator of this effect. These agents induce Cl- secretion only in
      cells expressing the wild-type CFTR, indicating that this molecule is the final
      common effector of the signaling pathway. The involvement of CFTR suggests a
      possible cystic fibrosis heterozygote advantage against STa-induced diarrhea.

PMID- 7510637
TI  - Clinical and morphological characteristics associated with sudden cardiac death
      in patients with Chagas' disease.
AB  - The medical records of 24 patients with Chagas disease who died suddenly, between
      1982 and 1988, were examined in an attempt to determine the clinical profile of
      sudden death in Chagas disease. Patient age ranged from 33 to 72 years (average:
      51). Seventeen (70%) were male: Five (20%) were asymptomatic. Dyspnoea at rest
      was observed in 16 (66%) and palpitations in eight (33%). On physical
      examination, arrhythmias were observed in 14 (58%), ankle swelling in 13 (54%)
      and liver enlargement in 12 (50%) patients. Twenty-three (95%) patients had an
      abnormal resting electrocardiogram: ventricular premature contractions were
      observed in 19 patients (79%) and a left anterior fascicular block in 14 (58%).
      The chest X-ray revealed cardiomegaly in 20 patients (82%), which was moderate in
      three (13%) and severe in 11 (45%). At autopsy, mean heart weight was 496 g.
      Dilatation of all cardiac chambers was detected in 22 (91%), and apical aneurysm
      in 19 (79%) patients. When compared with symptomatic patients, asymptomatic
      patients with Chagas disease had a higher frequency of normal physical
      examination (3/5 vs 1/19, P < 0.004), normal chest X-ray (3/5 vs 1/19, P < 0.01),
      and a lower heart weight (400 +/- 43 g vs 521.58 +/- 146.26 g, P < 0.03). The
      majority of patients with Chagas disease who die suddenly have severe underlying
      myocardial disease. In some of them, however, sudden cardiac death may occur in
      the presence of minimal, if any, heart involvement.

PMID- 7510636
TI  - RNA binding specificity of hnRNP A1: significance of hnRNP A1 high-affinity
      binding sites in pre-mRNA splicing.
AB  - Pre-mRNA is processed as a large complex of pre-mRNA, snRNPs and pre-mRNA binding
      proteins (hnRNP proteins). The significance of hnRNP proteins in mRNA biogenesis
      is likely to be reflected in their RNA binding properties. We have determined the
      RNA binding specificity of hnRNP A1 and of each of its two RNA binding domains
      (RBDs), by selection/amplification from pools of random sequence RNA. Unique RNA
      molecules were selected by hnRNP A1 and each individual RBD, suggesting that the
      RNA binding specificity of hnRNP A1 is the result of both RBDs acting as a single
      RNA binding composite. Interestingly, the consensus high-affinity hnRNP A1
      binding site, UAGGGA/U, resembles the consensus sequences of vertebrate 5' and 3'
      splice sites. The highest affinity 'winner' sequence for hnRNP A1 contained a
      duplication of this sequence separated by two nucleotides, and was bound by hnRNP
      A1 with an apparent dissociation constant of 1 x 10(-9) M. hnRNP A1 also bound
      other RNA sequences, including pre-mRNA splice sites and an intron-derived
      sequence, but with reduced affinities, demonstrating that hnRNP A1 binds
      different RNA sequences with a > 100-fold range of affinities. These experiments
      demonstrate that hnRNP A1 is a sequence-specific RNA binding protein. UV light
      induced protein-RNA crosslinking in nuclear extracts demonstrated that an
      oligoribonucleotide containing the A1 winner sequence can be used as a specific
      affinity reagent for hnRNP A1 and an unidentified 50 kDa protein. We also show
      that this oligoribonucleotide, as well as two others containing 5' and 3' pre
      mRNA splice sites, are potent inhibitors of in vitro pre-mRNA splicing.

PMID- 7510638
TI  - Endothelial-leukocyte adhesive interactions in inflammatory diseases.
AB  - There is evidence that vascular endothelium directs the accumulation of
      leukocytes in inflammation through various means, particularly by the expression
      of specific cell surface molecules which are adhesive for ligands on circulating
      leukocytes. Examples of such molecules are E-selectin and intercellular adhesion
      molecule 1 (ICAM-1). In an experimental model of various forms of inflammation, E
      selectin and ICAM-I were induced in association with adhesion and emigration of
      circulating polymorphonuclear and mononuclear leukocytes. Further work in humans
      showed endothelium to express E-selectin in inflammation. In addition, the
      presence of a leukocyte ligand for E-selectin, sialyl-Lewis X, has been seen on
      cells accumulating in inflammation. Furthermore, sialyl-Lewis X was also
      unexpectedly seen on endothelium. The role of sialyl-Lewis X on endothelium is as
      yet uncertain, although it may function as an adhesion receptor for leukocytes.
      Other endothelial adhesion receptors, such as vascular cell adhesion molecule 1
      (VCAM-1), are described. Atherosclerosis shows many features in common with
      inflammation. These are discussed, and the demonstrated and potential relevance
      of endothelial adhesive phenomena in routine inflammation to those in
      atherosclerosis are reviewed. For example, a VCAM-1 homologue has been described
      on the endothelium over evolving atherosclerotic lesions in rabbits.

PMID- 7510639
TI  - Src homology 2 domains of protein tyrosine phosphatase are associated in vitro
      with both the insulin receptor and insulin receptor substrate-1 via different
      phosphotyrosine motifs.
AB  - To clarify the role of protein tyrosine phosphatase containing Src homology 2
      (SH2) regions on insulin signaling, we investigated the interactions among the
      insulin receptor, a pair of SH2 domains of SH-PTP2 coupled to glutathione-S
      transferase (GST) and insulin receptor substrate-1 (IRS-1)-GST fusion protein
      (amino-portion, IRS-IN; carboxyl portion, IRS-1C). GST-SH2 protein of SH-PTP2
      bound to the wild type insulin receptor, but not to that with a carboxyl-terminal
      mutation (Y/F2). Furthermore, even though Y/F2 receptors were used, the SH2
      protein was also co-immunoprecipitated with IRS-IC, but not with IRS-IN. These
      results indicate that SH2 domains of SH-PTP2 can directly associate with the
      Y1322TXM motif on the carboxyl terminus of insulin receptors and also may bind to
      the carboxyl portion of IRS-1, possibly via the Y1172IDL motif in vitro.

PMID- 7510635
TI  - The N-terminal domain of the human TATA-binding protein plays a role in
      transcription from TATA-containing RNA polymerase II and III promoters.
AB  - In eukaryotes, the TATA box binding protein (TBP) is an integral component of the
      transcription initiation complexes of all three classes of nuclear RNA
      polymerases. In this study we have investigated the role of the N-terminal region
      of human TBP in transcription initiation from RNA polymerase (Pol) I, II and III
      promoters by using three monoclonal antibodies (mAbs). Each antibody recognizes a
      distinct epitope in the N-terminal domain of human TBP. We demonstrate that these
      antibodies differentially affect transcription from distinct classes of
      promoters. One antibody, mAb1C2, and a synthetic peptide comprising its epitope
      selectively inhibited in vitro transcription from TATA-containing, but not from
      TATA-less promoters, irrespective of whether they were transcribed by Pol II or
      Pol III. Transcription by Pol I, on the other hand, was not affected. Two other
      antibodies and their respective epitope peptides did not affect transcription
      from any of the promoters tested. Order of addition experiments indicate that
      mAb1C2 did not prevent binding of TBP to the TATA box or the formation of the TBP
      TFIIA-TFIIB complex but rather inhibited a subsequent step of preinitiation
      complex formation. These data suggest that a defined region within the N-terminal
      domain of human TBP may be involved in specific protein-protein interactions
      required for the assembly of functional preinitiation complexes on TATA
      containing, but not on TATA-less promoters.

PMID- 7510640
TI  - A phosphorothioate oligonucleotide blocks reverse transcription via an antisense
      mechanism.
AB  - We have studied the inhibition by a phosphorothioate oligodeoxynucleotide
      (17PScap) of cDNA synthesis performed by either avian or murine reverse
      transcriptase. Three different mechanisms of inhibition were identified: at low
      concentrations (< 100 nM), the cleavage of the RNA template by the retroviral
      RNase H at the level of the RNA/17PScap duplex accounted for most of the effect,
      whereas hybrid-arrested cDNA synthesis by an RNase H-independent mechanism
      marginally contributed to the inhibition. Both mechanisms were sequence-specific.
      Above 100 nM, the overall cDNA synthesis was reduced in a non-specific manner.

PMID- 7510641
TI  - Formation of a glycosylinositol-phosphate anchored high affinity Fc-receptor in
      COS cells.

PMID- 7510642
TI  - Stimulation of endocytosis by antibody cross-linking of the human high affinity
      receptor for IgG in COS cells is independent of the cytoplasmic and transmembrane
      domains.

PMID- 7510643
TI  - Mechanism of integrin alpha 4 beta 1-VCAM-1 interaction.

PMID- 7510644
TI  - Vasopressin stimulates phospholipase D, protein synthesis and RNA accretion in L6
      myoblasts.

PMID- 7510645
TI  - MAP kinase may play a role in the early phase of glucose transport in insulin
      treated 3T3-L1 fibroblasts.

PMID- 7510646
TI  - Acidic fibroblast growth factor or endothelin-1 stimulate the MAP kinase cascade
      in cardiac myocytes.

PMID- 7510647
TI  - Growth hormone-induced protein tyrosine phosphorylation in 3T3-F442A cells.

PMID- 7510648
TI  - Evolution of enhancer domains within the preprotachykinin promoter.

PMID- 7510649
TI  - Thapsigargin activates lymphocytes via a different pathway from ionomycin.

PMID- 7510650
TI  - Calphostin C inhibits endothelial cell proliferation and selectively modulates
      cell-surface marker expression.

PMID- 7510651
TI  - A nitric oxide synthase inhibitor reduces desensitisation of bradykinin-induced
      activation of phospholipase C in sensory neurones.

PMID- 7510653
TI  - Methylgenesis from betaine in cystathionine-beta-synthase deficiency.

PMID- 7510652
TI  - Tyrosine phosphorylation of proteins during "priming" of neutrophils.

PMID- 7510657
TI  - Chronic pancreatitis: management of pain.
AB  - Pain is the main symptom in chronic pancreatitis (CP). Since frequency, duration,
      severity and cause of pain in CP differ in patients, pain management becomes a
      challenge for physicians, which often requires a multidisciplinary approach. The
      first step is the exclusion of any anatomic abnormality (e.g. pseudocysts,
      compression of adjacent visceral structures) that could be the origin of pain.
      Medical measures such as abstinence from alcohol, use of analgesics, and
      suppression of exocrine pancreatic secretion may be useful, mainly in patients
      with early- to moderate-stage CP. Endoscopic interventions may alleviate pain in
      some selected cases. When nonoperative measures fail to alleviate pain and pain
      interferes significantly with the quality of life, surgery should be considered.
      Celiac plexus block and epidural anesthesia are procedures to be used only in
      selected cases.

PMID- 7510655
TI  - Sleep disorder and epilepsy in children with tuberous sclerosis: a questionnaire
      based study.
AB  - Sleep disorders were investigated in 40 children with tuberous sclerosis (TS) and
      compared with those found in non-disabled children and those reported in a mixed
      group with learning disabilities. Significantly higher levels of sleep
      disturbance were found in the TS group compared with both other groups. Within
      the TS group, current epilepsy and a high level of daytime behavioural
      disturbance were significantly associated with sleep disturbance, but pervasive
      developmental delay and high parental stress levels were not. Detailed study of
      the relationship between seizure activity and sleep disturbance in tuberous
      sclerosis is needed.

PMID- 7510656
TI  - 3-Methylglutaconic aciduria in the Iraqi-Jewish 'optic atrophy plus' (Costeff)
      syndrome.
AB  - Eleven new patients of Iraqi-Jewish origin with bilateral optic atrophy,
      neurological abnormalities ('optic atrophy plus' syndrome) and 3-methylglutaconic
      aciduria (type III) are described. Clinical abnormalities in decreasing order of
      frequency were bilateral optic atrophy, extrapyramidal signs, spasticity, ataxia,
      dysarthria and cognitive deficit. An association with age was found only for
      spasticity. Spasticity, extrapyramidal signs and optic atrophy frequently led to
      major disability, in contrast to ataxia, dysarthria and cognitive deficit. The
      combined excretion of 3-methylglutaconic and 3-methylglutaric acid ranged between
      9 and 187 mmol/mol creatinine. The primary enzymatic defect possibly may reside
      in the mitochondrial respiratory chain.

PMID- 7510654
TI  - IgG Fc receptors that resemble class I major histocompatibility complex antigens.
AB  - (1) The intestinal Fc receptors of neonatal rats and mice consists of beta 2m and
      an alpha-chain that is similar to those of MHC class I and CD1 antigens. (2)
      Mouse and rat FcRns are highly conserved. There are no amino acid substitutions
      in the 90 amino acid alpha 3 domain, and only one in the 40 amino acid
      cytoplasmic tail. (3) Despite its similarity to class I MHC antigens, the mouse
      FcRn alpha-chain is encoded outside the MHC, on chromosome 7.

PMID- 7510658
TI  - Localization of promoters in the fim gene cluster and the effect of H-NS on the
      transcription of fimB and fimE.
AB  - The expression of type 1 fimbriae in Escherichia coli undergoes phase variation
      in which individual bacteria switch between a fimbriated and non-fimbriated
      state. The transition from one state to the other is caused by inversion of a DNA
      segment containing the promoter for the fimA gene. The orientation of the
      invertible segment is controlled by two proteins, FimB and FimE, which mediate an
      on/off and off only orientation of the segment, respectively. In this study we
      have mapped the 5' termini of the fimB, fimE and fimA transcripts. Furthermore,
      we show that expression of fimB and fimE is strongly influenced by the H-NS
      nucleoid protein.

PMID- 7510660
TI  - Dose-response relationship in skin sensitization.
AB  - The dose-response relationship (challenge phase) of the skin sensitization
      response was investigated in previously sensitized Hartley guinea pigs. Larger
      numbers of animals were used per group at the lower doses so that statistically
      significant observations could be made. Model compounds known to be skin
      sensitizers were used: a strong sensitizer, dinitrochlorobenzene (DNCB), and a
      weaker sensitizer, p-phenylenediamine (PPDA). A gradation in response to changing
      DNCB doses was easily observed by using either the open epicutaneous test (OET)
      or the Buehler occlusive patch test. The Buehler test was used to study the dose
      response relationship of DNCB sensitization. The sensitivity of the OET and
      Buehler test was judged not adequate to measure the dose response for PPDA,
      because at high doses a high incidence of responders was not obtained. Therefore,
      the maximization test was used to evaluate PPDA. Similar, non-linear dose
      response curves were obtained with each compound. The higher doses produced a
      somewhat linear relationship, but at lower doses the curves flattened out and
      more slowly approached a zero response. Thus, for potent sensitizers,
      concentrations found in exposure situations might be in the linear portion of the
      dose-response curve. For weak responders, use concentrations might be in the
      shallow portion of the curve, where reactions would be underestimated if a linear
      dose-response curve were assumed.

PMID- 7510659
TI  - Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and
      hydroxytyrosol.
AB  - Antioxidants minimize oxidation of the lipid components in foods. There is an
      increasing interest in the use of natural and/or synthetic antioxidants in food
      preservation, but it is important to evaluate such compounds fully for both
      antioxidant and pro-oxidant properties. The properties of thymol, carvacrol, 6
      ginerol, hydroxytyrosol and zingerone were characterized in detail. Thymol,
      carvacrol, 6-gingerol and hydroxytyrosol decreased peroxidation of phospholipid
      liposomes in the presence of iron(III) and ascorbate, but zingerone had only a
      weak inhibitory effect on the system. The compounds were good scavengers of
      peroxyl radicals (CCl3O2; calculated rate constants > 10(6) M-1 sec-1) generated
      by pulse radiolysis. Thymol, carvacrol, 6-gingerol and zingerone were not able to
      accelerate DNA damage in the bleomycin-Fe(III) system. Hydroxytyrosol promoted
      deoxyribose damage in the deoxyribose assay and also promoted DNA damage in the
      bleomycin-Fe(III) system. This promotion was inhibited strongly in the
      deoxyribose assay by the addition of bovine serum albumin to the reaction
      mixtures. Our data suggest that thymol, carvacrol and 6-gingerol possess useful
      antioxidant properties and may become important in the search for 'natural'
      replacements for 'synthetic' antioxidant food additives.

PMID- 7510661
TI  - Successful prevention and treatment of autoimmune encephalomyelitis by short-term
      administration of anti-T-cell receptor alpha beta antibody.
AB  - To identify an effective immunotherapy for T-cell-mediated autoimmune diseases,
      prevention and treatment of experimental autoimmune encephalomyelitis (EAE)
      induced in Lewis rats was attempted by administering a monoclonal antibody (mAb),
      R73, which is specific for rat T-cell receptor (TcR) alpha beta. Short-term
      administration of R73 at relatively low doses before immunization with
      encephalitogenic antigen, myelin basic protein (MBP), prevented the development
      of EAE. However, treatment with anti-CD4 and anti-Ia mAb in the same protocol was
      ineffective. Flow cytometric analysis demonstrated that short-term administration
      of R73 resulted in transient down-regulation of the TcR molecules, whereas the
      number of CD2-expressing T cells was well preserved. Furthermore, the response to
      MBP of T cells isolated from rats that were pretreated with R73 and then
      immunized with MBP was strongly suppressed. On the other hand, the T-cell
      response of R73-pretreated rats to a third-party antigen which was immunized at a
      later period was not inhibited. These findings suggest that in vivo
      administration of a low dose of R73 protects rats from EAE by inducing anergy of
      MBP-reactive encephalitogenic T cells. Furthermore, R73 treatment which started
      on day 10 of the immunization (shortly before the day of onset of clinical signs)
      completely suppressed the induction of EAE and that which started on day 11 (the
      day of onset) hastened recovery. Since the phenotypes of the TcR V beta chain of
      encephalitogenic T cells are not so limited as previously believed, immunotherapy
      with mAb against the TcR alpha beta framework may be one of the best methods for
      treatment of T-cell-mediated autoimmune diseases.

PMID- 7510662
TI  - Similar CD40 ligand expression on EL-4 thymoma cell lines with widely different
      helper activity for B lymphocytes.
AB  - A mutagenized subclone of the murine EL-4 thymoma (clone B5) is approximately 30
      times more potent than parental EL-4 cells in stimulating proliferation and Ig
      secretion of murine or human B cells by direct cell contact in the presence of
      appropriate cytokines. In this study we found that CD40 ligand (CD40L) expression
      was constitutive and very similar on EL-4 B5 and parental EL-4 cells according to
      Northern blot and flow cytometry. Activation with phorbol 12-myristate 13-acetate
      (PMA) alone, PMA and ionomycin, interleukin-1 (IL-1) or human T-cell supernatant
      did not lead to significant CD40L up-regulation. A receptor-binding assay with
      soluble CD40 did not reveal different ligand affinities. However, murine and
      human soluble CD40-IgFc fusion proteins inhibited human B-cell stimulation by EL
      4 B5 cells in the presence of human T-cell supernatant. Inhibition was 96% when
      soluble CD40 was added on day 0 of culture and progressively decreased when the
      CD40 was added subsequently. Ig secretion by cytoplasmic Ig-positive cells was no
      longer inhibited. These findings imply that, although CD40 ligand is necessary
      for B-cell activation by EL-4B5 cells, additional molecule(s) must be responsible
      for the increased helper activity of the EL-4 B5 clone.

PMID- 7510664
TI  - Promotion of natural killer cell growth in vitro by bispecific (anti-CD3 x anti
      CD16) antibodies.
AB  - Bispecific heteroconjugated F(ab')2 fragments were prepared from pepsin-digested
      monoclonal OKT3 (anti-CD3) and 3G8 (anti-CD16) antibodies with 5,5'-dithiobis- (2
      nitrobenzoic acid). When these bispecific antibodies (BsA) were added to
      peripheral blood lymphocyte (PBL) cultures with 100 U/ml human recombinant
      interleukin-2 (rIL-2), preferable growth of natural killer cells occurred. After
      3 weeks the frequencies of CD56+ and CD56+3- cells in cultures with BsA were 74
      +/- 7% and 65 +/- 7%, respectively, compared with 48 +/- 6% and 29 +/- 7% in
      control cultures. The frequencies of CD3+ lymphocytes in the presence of BsA,
      cells from 1-day cultures were labelled with fluorescein isothiocyanate (FITC)
      conjugated anti-CD3, CD4 and CD8 monoclonal antibodies (mAb) and propidium iodide
      which stains dead cells. Flow cytometry revealed that more than 95% of the dead
      cells in cultures with BsA were CD3+. Thirty-seven per cent of CD3+, 43% of CD4+
      and 17% of CD8+ cells were dead on day 1, and after 3 days the CD4+/CD8+ ratio
      among viable lymphocytes was 1.6 in the control and 0.5 in BsA cultures. Taken
      together, these results show that bispecific (anti-CD3 x anti-CD16) F(ab')2
      fragments are strongly immunomodulatory by inducing the killing of T cells by
      CD16+ cells.

PMID- 7510665
TI  - In vivo immunosuppressive activity of gliotoxin, a metabolite produced by human
      pathogenic fungi.
AB  - Aspergillosis is a disease caused by the opportunistic pathogen Aspergillus
      fumigatus and other related fungi. It occurs mainly in immunosuppressed people
      and causes very high mortality rates. A fumigatus and other pathogenic fungi have
      been shown to produce a metabolite, gliotoxin, which has immunosuppressive
      properties in vitro, but little is known about its in vivo activity. Here we
      report that gliotoxin has increased toxicity in mice after irradiation. A single
      injection of gliotoxin delayed the recovery of immune cells after
      immunosuppression by sublethal irradiation by 2 weeks. Study of the morphology of
      cells of the thymus, spleen, and mesenteric lymph nodes by light microscopy and
      electron microscopy and agarose gel electrophoresis of DNA from these organs
      showed that the injection of gliotoxin induced apoptosis in cells of the immune
      system in vivo. Thus, gliotoxin does have immunosuppressive activity in vivo and
      could potentially play a significant role in the pathogenesis of aspergillosis
      and other fungal diseases.

PMID- 7510663
TI  - Molecular basis of cross-reactivity among allergen-specific human T cells: T-cell
      receptor V alpha gene usage and epitope structure.
AB  - Cross-reactivities between the major grass pollen allergens, at the level of T
      cell recognition was examined employing several Lolium perenne I (Lol p I)
      specific human T-cell clones. Nine of these Lol p I-specific T-cell clones
      exhibited cross-recognition of the recombinant Poa pratensis IX (Poa p IX)
      allergen, rKBG7.2, indicating that these two major antigens of a grass pollen
      share T-cell epitopes. Furthermore, proliferative responses of two other T-cell
      clones demonstrated that individual allergens of diverse grass pollens also
      possess common T-cell epitopes. Examination of the T-cell receptor (TcR) V alpha
      genes of these T-cell clones indicated that these cloned cells utilized distinct
      J alpha genes and that nine out of 10 clones possessed V alpha 13 gene.
      Furthermore, sequence comparisons of several allergenic molecules indicated that
      this cross-reactivity may be due to the presence of epitope(s) with structure(s)
      similar to the major T-cell epitope of Poa p IX allergens. Taken together, these
      results suggest for the first time that the major grass pollen allergens share
      cross-reacting T-cell epitope(s), and that this cross-reactivity is due to the
      structural homologies among allergens and restricted usage of TcR V alpha genes.

PMID- 7510666
TI  - Size heterogeneity among antigenically related Giardia lamblia variant-specific
      surface proteins is due to differences in tandem repeat copy number.
AB  - Giardia lamblia undergoes antigenic variation by modulating the expression of the
      different genes that comprise the trophozoite's variant-specific surface protein
      (VSP) repertoire. We studied an epitope that is conserved among VSPs expressed by
      cloned trophozoite lines derived from the independent G. lamblia isolates WB,
      G3M, Be-2, and CAT. The epitope recognized by monoclonal antibody 6E7 lies
      entirely within the region of tandemly repeated 65-amino-acid units that is
      characteristic of these size-variant VSPs. Northern (RNA) hybridization, cDNA
      cloning, and DNA sequence analysis indicate that size heterogeneity among these
      VSPs is due to differences in the number of repetitive units.

PMID- 7510667
TI  - A murine monoclonal antibody defines a unique epitope shared by Klebsiella
      lipopolysaccharides.
AB  - A hybridoma secreting a monoclonal antibody (MAb) directed against Klebsiella
      lipopolysaccharide (LPS) was derived from spleen cells of mice immunized a
      smooth, nonencapsulated Klebsiella strain (Friedlander 201; serogroup O1). The
      MAb, called V/9-5 (immunoglobulin G2a), cross-reacted with LPS preparations
      produced from reference strains for the Klebsiella O serogroups O1, O2ab, O2ac,
      O3, O4, O5, and O12. Furthermore, the MAb reacted with LPSs from serogroup
      reference strains O6/O8, O9, and O11, which are regarded as being identical to
      O1, O2, and O4, respectively. When testing the supernatant of clinically isolated
      Klebsiella strains by means of an inhibition enzyme-linked immunosorbent assay,
      we found that 86 (92.4%) of 93 Klebsiella pneumoniae subsp. pneumoniae isolates
      and 24 (96.0%) of 25 K. oxytoca isolates harbored the cross-reactive epitope. By
      contrast, two laboratory strains of K. pneumoniae subsp. rhinoscleromatis did not
      react with MAb V/9-5. The MAb proved to be specific for the genus Klebsiella,
      since it did not react with any of a total of 73 strains belonging to other gram
      negative bacterial genera. In conjunction with other LPS-specific MAbs, MAb V/9-5
      might become a useful reagent for rapid identification of klebsiellae in clinical
      specimens. Furthermore, the epitope recognized by MAb V/9-5 might serve as a
      target epitope for the production of human MAbs for immunotherapeutic purposes.

PMID- 7510668
TI  - Antigenic diversity in the circumsporozoite protein of Plasmodium falciparum
      abrogates cytotoxic-T-cell recognition.
AB  - Genetic analysis of field isolates of Plasmodium falciparum has shown selective
      accumulation of point mutations within the immunologically sensitive sites of the
      circumsporozoite (CS) protein, a vaccine candidate against malaria. This raised
      concern whether a vaccine containing the sequence of a selected strain of P.
      falciparum would be able to confer protection against other variant parasites.
      The answer to this question remained speculative, and in this study, we have
      formally tested the immunological impact of such natural variations within a
      known cytotoxic-T-cell (CTL) epitope, which is recognized by both human and
      murine CTLs. With a murine model, CTLs were generated against the 7G8 strain of
      P. falciparum. The ability of these CTLs to lyse histocompatible targets that
      were pulsed with synthetic peptides corresponding to polymorphic sequences of
      Brazilian, Papua New Guinean, and The Gambian isolates was determined. While
      these CTLs were able to recognize three of the four variant CS sequences found in
      Brazil and Papua New Guinea, they failed to recognize four of the five variant CS
      sequences found in The Gambia. Among the peptides that lost their reactivity to
      7G8-specific CTL, all except one had amino acid variation in more than one
      residue. On the other hand, only one of the four peptides that showed a positive
      reaction had amino acid substitutions in more than a single residue. Thus, our
      findings demonstrate that natural amino acid variations in the CS protein
      abrogate CTL recognition. Therefore, it is important to consider the implications
      of these results in designing CS protein-based vaccines.

PMID- 7510669
TI  - Differential interaction of Escherichia coli heat-labile toxin and cholera toxin
      with pig intestinal brush border glycoproteins depending on their ABH and related
      blood group antigenic determinants.
AB  - The ability of glycoproteins from pig intestinal brush border membranes (BBM) to
      bind cholera toxin (CT) or heat-labile toxins from strains of Escherichia coli
      isolated from human (LTh) or pig (LTp) intestines was studied. Glycoproteins
      capable of binding the toxins are also recognized by antibodies or lectins
      specific for ABO(H) blood group and related antigens. Pigs expressing A, H, or I
      antigenic determinants were used for comparison. The toxin-binding capacity of a
      glycoprotein depends on the toxin type and the blood group epitope borne by the
      glycoprotein. LTh and LTp preferably bound to several blood group A-active
      glycoproteins rather than H-active glycoproteins. By contrast, CT practically did
      not recognize either blood group A- or blood group H-active glycoproteins, while
      glycoproteins from pigs expressing I antigenic determinants were able to interact
      with LTh, LTp, and CT. LTh, LTp, or CT glycoprotein binding was selectively
      inhibited by specific lectins or monosaccharides. Affinity purification of the
      toxin binding brush border glycoproteins on the basis of their blood group
      reactivity suggests that such glycoproteins are hydrolytic enzymes. BBM from A+
      pigs contain about 27 times more LTh binding sites, in addition to those
      recognized by CT, than an equivalent membrane preparation from H+ pigs. The
      present findings may help clarify some previous unclear results on LTh binding to
      intestinal BBM glycoproteins obtained by use of animals not typed by their ABO(H)
      blood group phenotype.

PMID- 7510670
TI  - Expression of inducible nitric oxide synthase by stimulated macrophages
      correlates with their antihistoplasma activity.
AB  - The antihistoplasma activity of recombinant murine gamma interferon (rMuIFN
      gamma)-treated macrophages of the RAW 264.7 cell line depends on the generation
      of nitric oxide (NO.) from L-arginine. Macrophages of the P388D1 cell line
      treated with rMuIFN-gamma do not produce NO. or inhibit the intracellular growth
      of Histoplasma capsulatum. NO. is generated by the inducible enzyme nitric oxide
      synthase (iNOS) formed by stimulated macrophages. Northern (RNA) blot analysis of
      RAW 264.7 cells revealed the expression of iNOS mRNA after exposure to rMuIFN
      gamma. In contrast, rMuIFN-gamma-treated P388D1 cells did not produce detectable
      levels of iNOS. These data suggest that the failure of P388D1 cells to generate
      NO. and to restrict the intracellular growth of H. capsulatum is due to a lack of
      expression of iNOS following treatment with rMuIFN-gamma.

PMID- 7510671
TI  - Comparison of Vibrio cholerae O139 with V. cholerae O1 classical and El Tor
      biotypes.
AB  - Vibrio cholerae O139 is a recently identified non-O1 V. cholerae strain
      responsible for outbreaks of epidemic cholera in India, Bangladesh, and Thailand
      in the past 2 years. Other workers have demonstrated the presence of the cholera
      toxin genetic element in V. cholerae O139, unlike the situation for other non-O1
      V. cholerae strains. We sought to compare further this strain with strains of V.
      cholerae O1, classical and El Tor biotypes, by classic microbiologic methods,
      Southern blot analysis for restriction fragment length polymorphisms with probes
      for iron-regulated genes of V. cholerae O1, and comparisons of outer membrane
      protein profiles. Our results were similar for V. cholerae O139 and the El Tor
      biotype of V. cholerae O1, with the exception of the constitutive expression in
      V. cholerae O139 of OmpS, an outer membrane protein that was maltose inducible in
      comparison strains of V. cholerae O1.

PMID- 7510672
TI  - Influence of three different preparation techniques on the results of human sperm
      morphology analysis.
AB  - Using 158 unselected semen samples the present study has analysed how the results
      of sperm morphology assessment were influenced by different techniques for
      preparing the slides for microscopic assessment. All three techniques compared,
      the Papanicolaou stain (PAP), the Shorr stain (SHO) and the 'wet preparations'
      protocol (WET) are currently recommended by the World Health Organization for use
      in andrology laboratories. Mean percentages of morphologically normal spermatozoa
      were identical on PAP and SHO slides (31.1%), but were significantly lower in wet
      preparations (12.3%). Wide divergence of results obtained with the three
      different methods was also found with respect to the percentage of sperm with
      head, midpiece and tail defects and two 'indices of teratozoospermia'. For the
      majority of parameters assessed, linear regression analysis revealed a poor
      correlation between evaluations of PAP, SHO and WET slides (r values ranging from
      0.01 to 0.87). We conclude that only one standard method should be recommended
      for the preparation of morphology slides in order to ensure inter-laboratory
      comparability of results and to enhance the value of sperm morphology analysis
      for predicting fertility.

PMID- 7510673
TI  - A proposed mechanism for the action of strong static magnetic fields on
      biomembranes.
AB  - Experimental studies have demonstrated a temperature dependent effect by strong
      static magnetic fields on synaptic function. It is proposed that these findings
      may be explained by the diamagnetic properties of membrane phospholipids. The
      change in diamagnetic anisotropy coincidental with membrane thermotropic phase
      transition is responsible for the temperature dependence of this phenomenon and
      provides insight into the mechanism of action of these fields. At the prephase
      transition temperature highly diamagnetic anisotropic gel phase domains exist
      within a more fluid liquid-crystal phase. The partial magnetic reorientation of
      these domains results in membrane distortion and, thereby, functional impairment
      of contiguous ion specific channels. This mechanism adequately explains
      observations of the effects of static magnetic fields both on the central nervous
      system and at the neuromuscular junction. It is suggested that the same mechanism
      may be operative in other biosystems.

PMID- 7510674
TI  - An efficient Shine-Dalgarno sequence but not translation is necessary for lacZ
      mRNA stability in Escherichia coli.
AB  - The 5' ends of many bacterial transcripts are important in determining mRNA
      stability. A series of Shine-Dalgarno (SD) sequence changes showed that the
      complementarity of the SD sequence to the anti-SD sequence of 16S rRNA correlates
      with lacZ mRNA stability in Escherichia coli. Several initiation codon changes
      showed that an efficient initiation codon is not necessary to maintain lacZ mRNA
      stability. A stop codon in the 10th codon of lacZ increased mRNA stability.
      Therefore, ribosomal binding via the SD sequence but not translation of the
      coding region is necessary to maintain lacZ mRNA stability.

PMID- 7510676
TI  - Rapid changes in nuclear protein tyrosine phosphorylation after growth hormone
      treatment in vivo. Identification of phosphorylated mitogen-activated protein
      kinase and STAT91.
AB  - Growth hormone (GH) plays a central role in regulating growth and intermediary
      metabolism in vertebrates, although the mechanisms by which GH initiates these
      actions are largely unknown. The GH receptor, a member of the cytokine receptor
      superfamily, does not demonstrate homology with any known tyrosine kinases.
      However, addition of GH to cells in vitro has been shown to stimulate tyrosine
      phosphorylation of various intracellular proteins including mitogen-activated
      protein kinases (MAP kinases) and the newly described Janus kinase, JAK2.
      Subsequent steps in GH-mediated signal transduction have not been delineated. In
      the present study, we have examined early events in GH action in vivo.
      Hypophysectomized juvenile male rats were treated with GH for 15, 30, or 60 min.
      Rat liver whole cell and nuclear extracts were prepared and analyzed via SDS
      polyacrylamide gel electrophoresis and Western blotting techniques. GH rapidly
      stimulated the tyrosine phosphorylation of at least 8 nuclear proteins of 205,
      91, 83, 80, 65, 53, 44, and 42 kDa, and caused the dephosphorylation of a single
      approximately 149-kDa protein. Using specific antibodies, we have identified
      three of these nuclear phosphoproteins as 42- and 44-kDa MAP kinases, and as
      STAT91, a 91-kDa component of the interferon-stimulated gene factor-3 protein
      complex. One consequence of the activation of STAT91 in the nucleus is the
      appearance of GH-stimulated DNA binding activity, as assessed by gel-mobility
      shift assay using an oligonucleotide containing a c-sis-inducible element from
      the c-fos promoter. These results show that nuclear protein tyrosine
      phosphorylation is a prominent early event in GH action in vivo and demonstrate a
      link between GH-stimulated signal transduction and target gene expression.

PMID- 7510677
TI  - Tyrosine phosphorylation of protein phosphatase 2A in response to growth
      stimulation and v-src transformation of fibroblasts.
AB  - The catalytic subunit of protein phosphatase 2A (PP2A) is inactivated by in vitro
      phosphorylation of Tyr307 by receptor and nonreceptor protein tyrosine kinases
      (Chen, J., Martin, B. L., and Brautigan, D. L. (1992) Science 257, 1261-1264).
      Here we show the phosphorylation of PP2A in cells under different growth
      conditions. In lysates of nontransformed murine 10T1/2 fibroblasts, there were
      two forms of PP2A at 36 kDa detected after two-dimensional gel electrophoresis
      and immunoblotting with anti-PP2A peptide antibody. These two forms exactly
      comigrated with unphosphorylated purified PP2A and the PP2A 32P-labeled by in
      vitro phosphorylation with p60v-src kinase. The phosphorylated form of PP2A
      recovered from red blood cells or produced by in vitro phosphorylation was
      eliminated by incubation with tyrosine-specific phosphatase (PTP1B).
      Transformation of 10T1/2 cells by expression of p60v-src resulted in most of the
      PP2A in the cells being converted to a phosphorylated form that was reactive with
      anti-phosphotyrosine antibody. Serum starvation of cells reduced the amount of
      phosphorylated PP2A, whereas serum stimulation of quiescent cells caused an
      increase to the same relative amount of phosphorylated PP2A as in src-transformed
      cells. Addition of epidermal growth factor to quiescent NeoR cells (10T1/2
      fibroblasts overexpressing epidermal growth factor receptors) temporarily
      increased the level of phosphorylation of PP2A, with a peak at 5-15 min and a
      return to basal level within 60 min. The results show that PP2A is phosphorylated
      in intact cells, and the extent of this modification is increased by growth
      factors or cell transformation, providing evidence for a physiological mechanism
      of PP2A regulation.

PMID- 7510675
TI  - NusA changes the conformation of Escherichia coli RNA polymerase at the binding
      site for the 3' end of the nascent RNA.
AB  - A conformational change in Escherichia coli RNA polymerase induced by NusA was
      detected by utilizing photocrosslinking. A change in the binding site for the 3'
      end of the RNA occurred, and NusA increased interactions of the RNA with the beta
      subunit of the polymerase. NusA was not contacted by the 3' end of the RNA.

PMID- 7510678
TI  - Regulation of nitric-oxide synthase mRNA expression by interferon-gamma and
      picolinic acid.
AB  - Picolinic acid, a catabolite of L-tryptophan, is a potent co-stimulatory agent
      for the induction of tumoricidal activity and the production of L-arginine
      dependent reactive nitrogen intermediates (RNI) in murine macrophages. We studied
      whether picolinic acid could affect nitric-oxide synthase (NOS) expression at the
      gene level in the macrophage cell line ANA-1. NOS mRNA was neither constitutively
      expressed nor induced by treatment with picolinic acid alone. However, low levels
      of NOS mRNA were induced by interferon (IFN)-gamma alone. In contrast, a major
      increase of NOS mRNA expression was observed after treatment with IFN-gamma plus
      picolinic acid. The synergism was already detectable after 5-6 h and increased up
      to 20 h of treatment. The ability of picolinic acid to augment IFN-gamma
      dependent NOS mRNA expression was associated with a parallel increase in
      transcription, as demonstrated by nuclear run-on experiments. Protein synthesis
      was required for the induction of NOS mRNA because addition of cycloheximide
      dramatically reduced IFN-gamma plus picolonic acid-induced NOS mRNA expression.
      Finally, interleukin-4 significantly decreased IFN-gamma plus picolinic acid
      induced NOS mRNA expression and NOS transcription. These data provide evidence of
      a molecular event connecting arginine and tryptophan metabolic pathways in the
      generation of RNI, and they indicate that picolinic acid can induce
      transcriptional activation of gene expression.

PMID- 7510683
TI  - Preferential inhibition of platelet-derived growth factor-stimulated DNA
      synthesis and protein tyrosine phosphorylation by nordihydroguaiaretic acid.
AB  - Nordihydroguaiaretic acid (NDGA), a reportedly specific lipoxygenase inhibitor,
      was found to selectively inhibit platelet-derived growth factor (PDGF)-stimulated
      DNA synthesis in Swiss 3T3 cells. Maximal inhibition of PDGF-induced
      [3H]thymidine incorporation (96%) was observed using 4 microM NDGA (IC50 = 1.5
      microM). No effect of NDGA was observed upon DNA synthesis stimulated with either
      fetal bovine serum, bombesin, or epidermal growth factor (EGF) in the presence of
      insulin, or with the potent mitogen Pasteurella multocida toxin. The selective
      inhibition of PDGF-stimulated DNA synthesis by NDGA was also observed in diploid
      murine cells, rat, and human fibroblasts. Furthermore, 4 microM NDGA also
      inhibited PDGF-stimulated anchorage-independent colony growth of rat-1 cells by
      76%. Using Swiss 3T3 cells, we found that PDGF-stimulated arachidonic acid
      mobilization and prostaglandin E2 production was abolished by NDGA in a dose
      dependent manner. Inhibition of PDGF-stimulated arachidonic acid mobilization by
      NDGA could not, however, explain its potent inhibitory effect upon PDGF
      stimulated DNA synthesis. Our results showed that NDGA also selectively inhibited
      PDGF receptor tyrosine phosphorylation in a dose-dependent manner in intact
      cells. Protein tyrosine phosphorylation stimulated by EGF or bombesin was not
      altered by NDGA treatment. Crucially, NDGA inhibited in vitro the tyrosine kinase
      activity of anti-phosphotyrosine and anti-PDGF receptor immunoprecipitates
      prepared from cultures stimulated with PDGF. This inhibition of receptor tyrosine
      phosphorylation in a cell-free system confirmed that NDGA acts directly at the
      level of the PDGF receptor tyrosine kinase domain. These results suggest that the
      potent and selective inhibitory effect of NDGA on PDGF-stimulated DNA synthesis
      results from its inhibitory action on tyrosine phosphorylation.

PMID- 7510681
TI  - Protein kinase C transiently activated heteromeric N-methyl-D-aspartate receptor
      channels independent of the phosphorylatable C-terminal splice domain and of
      consensus phosphorylation sites.
AB  - We have expressed dual subunit combinations of isoforms of the N-methyl-D
      aspartate receptor, NR1A-NR2A and NR1C-NR2A, in Xenopus oocytes. We show that
      both forms of the receptor are stereospecifically activated by low concentrations
      (10 nM) of the phorbol ester 4-beta-phorbol 12-myristate 13-acetate, known to
      activate protein kinase C (PKC). The activation is transient, and, after reaching
      a maximum in about 10 min, it decreases rapidly in spite of the continuous
      presence of phorbol ester. The addition of 2 microM oleoylacetylglycerol had
      similar consequences. NR1C differs from NR1A by a deletion of 37 amino acids that
      include four consensus phosphorylation sites for PKC in the C-terminal region.
      The corresponding peptide has been shown to become phosphorylated upon activation
      of PKC in neurons (Tingley, W. G., Roche, K. W., Thompson, A. K., and Huganir, R.
      L. (1993) Nature 364, 70-73). However, the activity of NR1C-NR2A receptors was
      stimulated 7-fold, twice the potentiation observed for NR1A-NR2A. By site
      specific mutagenesis of NR1C and NR2A, we removed additional consensus PKC
      phosphorylation sites located between TM3 and TM4. Coexpression of these mutant
      subunits showed a similar response to phorbol esters as wild type receptors. Our
      results indicate that neither the predicted consensus phosphorylation sites
      between transmembrane sequences TM3 and TM4 nor the phosphorylatable C-terminal
      splice domain is essential for the modulation of N-methyl-D-aspartate receptors
      by PKC.

PMID- 7510680
TI  - Lipopolysaccharide (LPS) binding protein, truncated at Ile-197, binds LPS but
      does not transfer LPS to CD14.
AB  - Lipopolysaccharide (LPS) binding protein (LBP), a 58-60 kDa glycoprotein, binds
      to the lipid A region of LPS. The resulting LPS-LBP complex is recognized by both
      the membrane-bound (mCD14) and soluble forms of CD14 (sCD14), thereby enhancing
      the ability of LPS to activate myeloid, endothelial, and epithelial cells. To
      begin to characterize the structure-function relationships within LBP, we have
      created and expressed a truncated form of human LBP (herein called NH-LBP)
      comprising amino acid residues 1-197 of the parent molecule. Experiments were
      done to characterize the ability of NH-LBP to bind LPS and to promote LPS binding
      to CD14. We found that NH-LBP efficiently binds LPS but does not transfer the LPS
      to either mCD14 or sCD14. Additionally, NH-LBP inhibited LPS binding to LBP,
      inhibited the LBP-promoted binding of LPS to CD14, and inhibited the LBP
      dependent activation of rabbit peritoneal exudate macrophages. The apparent
      dissociation constant for LPS-NH-LBP complexes is less than 1 x 10(-8) M which
      compares well with the dissociation constant for LPS-LBP complexes of
      approximately 1 x 10(-9) M. We conclude from these studies that the LPS binding
      site of LBP resides in the amino-terminal half of LBP and that the CD14
      interaction site resides in the carboxyl-terminal half of LBP. These data suggest
      that appropriately modified fragments of LBP might provide novel reagents with
      high LPS binding affinity that could be useful in inhibiting LPS-dependent
      cellular activation in vivo.

PMID- 7510679
TI  - Endocytosis of urokinase-plasminogen activator inhibitor type 1 complexes bound
      to a chimeric transmembrane urokinase receptor.
AB  - The urokinase receptor (uPAR) is linked to plasma membranes through a
      glycosylphosphatidylinositol (GPI) anchor. It has been posited that the GPI
      anchor facilitates clearance of uPAR-bound complexes between two chain urokinase
      (tcuPA) and plasminogen activator inhibitor type 1 (PAI-1) by the alpha 2
      macroglobulin receptor (alpha 2MR) which permits re-expression of unoccupied uPA
      receptors on the cell surface. To test this hypothesis we compared
      internalization and degradation of 125I-labeled tcuPA-PAI-1 by COS cells
      expressing either transfected wild-type, GPI-linked uPAR (uPAR/GPI), or a
      chimeric receptor composed of the extracellular domains of uPAR linked to the
      transmembrane and cytosolic domains of the alpha chain (p55 subunit) of the
      interleukin-2 receptor (uPAR/IL-2R alpha). The kinetics of binding,
      internalization and degradation of tcuPA-PAI-1 by COS cells expressing each form
      of uPAR were virtually identical. However, internalization of complexes by
      uPAR/IL-2R alpha was more susceptible to inhibition by recombinant soluble 39-kDa
      alpha 2MR-associated protein (RAP) which competes for binding of tcuPA-PAI-1
      complexes to alpha 2MR (p < 0.001), and the internalization was accompanied by a
      greater reduction in the number of surface uPAR/IL-2R alpha, than uPAR/GPI (p <
      0.05). These studies indicate that the rate of internalization of tcuPA-PAI-1 is
      governed primarily by the extracellular domains of uPAR, whereas the GPI anchor
      may facilitate internalization of complexes and re-expression of uPAR when
      binding sites on alpha 2MR are limiting.

PMID- 7510682
TI  - Two forms of phospholipase C-beta 1 generated by alternative splicing.
AB  - Phospholipase C-beta 1 (PLC-beta 1) exists as two immunologically
      indistinguishable polypeptides of 150 and 140 kDa and is encoded in rat brain by
      two distinct transcripts of 5.4 and 7.2 kilobases (kb). cDNA corresponding to the
      entire 5.4-kb transcript as reported previously reveals an open reading frame
      that is capable of coding a 1216-amino acid polypeptide (Suh, P. G., Ryu, S. H.,
      Moon, K. H., Suh, H. W., and Rhee, S. G. (1988) Cell 54, 161-169). We have now
      isolated cDNAs corresponding to the entire 7.2-kb transcript from a rat brain
      cDNA library. The 7.2-kb transcript differs from the previously reported 5.4-kb
      transcript by possessing both an additional 118 nucleotides located near the end
      of the coding sequence and a 1738-nucleotide extension of the 3'-flanking region.
      The presence of the 118-nucleotide insert in the cumulative 7.2-kb sequence gives
      rise to an open reading frame that is capable of coding a 1173-amino acid
      polypeptide (PLC-beta 1b), the carboxyl-terminal sequence of which differs from
      that of the 1216-amino acid polypeptide (PLC-beta 1a) derived from the 5.4-kb
      transcript. Antibodies were raised against synthetic peptides corresponding to
      the carboxyl-terminal portions of PLC-beta 1a and PLC-beta 1b. Immunoblot
      analysis with these isozyme-specific antibodies revealed that both PLC-beta 1a
      and PLC-beta 1b are expressed in rat brain and C6Bu-1 glioma cells and that PLC
      beta 1a and PLC-beta 1b correspond to the previously identified 150- and 140-kDa
      PLC-beta 1 enzymes, respectively. Analysis of PLC-beta 1 genomic DNA indicates
      that PLC-beta 1a and PLC-beta 1b are derived from a single gene by alternative
      RNA splicing.

PMID- 7510684
TI  - Biochemical and biophysical identification of cystic fibrosis transmembrane
      conductance regulator chloride channels as components of endocytic clathrin
      coated vesicles.
AB  - Cystic fibrosis results from mutations in the gene encoding the CFTR Cl- channel.
      Although CFTR occurs as an integral component of the plasma membrane, recent
      studies implicate CFTR in endocytic recycling and suggest that the protein may
      also exist in intracellular vesicular compartments. To test this, we analyzed
      CFTR in clathrin-coated vesicles (CCV) purified from cells constitutively
      expressing CFTR at high levels. CFTR immunoreactivity was detected in CCV by
      immunoblot and was identified as CFTR based on labeling of immunoprecipitates
      with protein kinase A and by tryptic phosphopeptide mapping. Fusion of uncoated
      CCV with planar lipid bilayers resulted in the incorporation of kinase- and ATP
      activated Cl- channel activity (7.8 pS at 20 degrees C; 11.9 pS at 37 degrees C),
      with a linear current-voltage relation under symmetrical conditions. Thus,
      functional CFTR occurs in CCV. Moreover, CFTR interacts with the plasma membrane
      specific adaptor complex during endocytosis through clathrin-coated pits.
      Therefore, the abundance of CFTR in the plasma membrane may be regulated by
      exocytic insertion and endocytic recycling, and these processes may provide an
      augmentation to protein kinase A activation as a mechanism for regulating CFTR Cl
      channels in the plasma membrane.

PMID- 7510686
TI  - Identification of a combinatorial epitope expressed by the integrin alpha 4 beta
      1 heterodimer involved in the regulation of cell adhesion.
AB  - The alpha 4 integrin subunit can associate with either the beta 1- or beta 7
      integrin subunit to form two unique adhesion receptors alpha 4 beta 1 and alpha 4
      beta 7. We developed a monoclonal antibody (mAb 19H8) that immunoprecipitated
      alpha 4 beta 1, induced homotypic leukocyte aggregation, and blocked the binding
      of cells to a synthetic peptide corresponding to the CS-1 peptide region of
      fibronectin. Aggregation cross-blocking analysis suggested that mAb 19H8 belonged
      to the group of mAbs that react with the B2 epitope of the alpha 4 subunit (alpha
      4.B2 epitope); however, unlike the alpha 4.B2-specific mAb L25, mAb 19H8 did not
      immunoprecipitate alpha 4 beta 7. In addition, mAb 19H8 did not bind to beta 1
      positive cells unless transfected with alpha 4 cDNA. These results indicated that
      mAb 19H8 was not specific for an individual alpha 4, beta 1, or beta 7 subunit
      but reacted with an epitope formed from the association of alpha 4 with beta 1.
      Separating the alpha 4 from the beta 1 subunit, by removing divalent cations or
      by treatment with high pH, disrupted mAb 19H8 binding. In contrast, the alpha 4
      specific mAb L25 and the beta 1-specific mAb 18D3 could react with their
      respective subunits without subunit association. Therefore, mAb 19H8 defined a
      novel regulatory epitope expressed by the integrin alpha 4 beta 1.

PMID- 7510687
TI  - Lipopolysaccharide binding protein expression in primary human hepatocytes and
      HepG2 hepatoma cells.
AB  - Lipopolysaccharide (LPS)-binding protein (LBP) is a normal plasma protein and an
      acute phase reactant important for host responses to Gram-negative bacteria and
      LPS. LBP forms high affinity complexes with LPS which bind to CD14, a monocyte
      surface protein, to initiate the release of inflammatory mediators. We found that
      human primary hepatocytes synthesize LBP and that the synthesis is up-regulated
      by interleukin (IL)-6. To examine this phenomenon in more detail, we evaluated
      the capacity of IL-6, IL-1, and tumor necrosis factor to induce LBP synthesis in
      HepG2 cells in the presence or absence of dexamethasone. IL-6 induced LBP
      synthesis. Dexamethasone, IL-1, and tumor necrosis factor had a synergistic
      effect when combined with IL-6, but demonstrated minimal effect independently.
      LBP biosynthesis was evaluated by immunoprecipitation of 35S-labeled LBP from
      HepG2 supernatants, measurement of steady-state LBP mRNA levels, and analysis of
      LBP-dependent LPS binding to CD14 positive cells. An 35S-labeled, 60-kDa protein
      was immunoprecipitated with anti-LBP antibody from IL-6-stimulated HepG2 cell
      supernatants. Northern blot analysis of cellular RNA revealed an increase in LBP
      mRNA in IL-6-stimulated cells. CD14 expressing cells bound fluoresceinated LPS in
      the presence of supernatants from HepG2 cells treated with IL-6. These data
      provide the first information about specific cytokine and dexamethasone
      regulation of LBP expression in HepG2 cells. LBP behaves like a Type 1 acute
      phase protein.

PMID- 7510685
TI  - Dual mechanism for the control of inducible-type NO synthase gene expression in
      macrophages during activation by interferon-gamma and bacterial
      lipopolysaccharide. Transcriptional and post-transcriptional regulation.
AB  - Production of nitric oxide (NO) by macrophages is enhanced upon activation by
      bacterial endotoxins and cytokines mainly via an increase of the intracellular
      content of the inducible isoform of nitric oxide synthase (i-NOS). We have
      studied in detail the effect of several modulators of macrophage activity on
      steady state levels of i-NOS mRNA in the mouse macrophage-like cell line RAW
      264.7. Bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) were
      found to be effective inducers of i-NOS mRNA, in accordance with their known
      ability to stimulate both i-NOS activity and NO production in macrophages from
      different sources, while TNF-alpha, IL-1, or IL-6 was ineffective in this regard.
      Accumulation of i-NOS mRNA in response to either LPS or IFN-gamma stimulation was
      accompanied by increased i-NOS gene transcription, as detected both by using a
      nuclear "run-on" transcription assay and by transient transfection of the cloned
      gene promoter in RAW 264.7 cells. Co-stimulation of the cells with both inducers
      resulted in higher steady state levels of i-NOS mRNA in the absence, however, of
      a corresponding potentiation of the rate of gene transcription. This was due
      primarily to a considerable effect of LPS on i-NOS mRNA stability, with
      prolongation of its half-life from 1-1.5 h, in the presence of IFN-gamma alone,
      to 4-6 h in the presence of both LPS and IFN-gamma.

PMID- 7510688
TI  - Two alternatively spliced forms of the human insulin-like growth factor I
      receptor have distinct biological activities and internalization kinetics.
AB  - Two alternatively spliced human insulin-like growth factor I (IGF I) receptor
      mRNA transcripts have been described that differ by three nucleotides (CAG)
      starting at position 2829. This results in an amino acid coding sequence change
      from Thr-Gly to Arg in the extracellular portion of the receptor beta subunit. To
      investigate the functional significance of this sequence difference, we obtained
      full-length cDNAs for the CAG+ and CAG- receptor forms, transfected CHO cells,
      and isolated multiple clones expressing approximately equal numbers of receptors
      (0.57-0.73 x 10(6) receptors/cell). The two receptors bound IGF I with similar
      affinity (Kd approximately 1.7 nM), but the CAG- form exhibited an approximately
      2-fold increase in IGF I stimulation of receptor autophosphorylation, insulin
      receptor substrate-1 (IRS-1) tyrosine phosphorylation, thymidine incorporation,
      and IRS-1-associated phosphatidylinositol 3-kinase activity. In contrast to its
      higher signaling activity, the rate of receptor-mediated internalization of IGF I
      by the CAG-receptor was decreased by 50% in comparison with the CAG+ receptor. We
      conclude that proteins corresponding to the two alternatively spliced human IGF I
      receptor transcripts are biologically active, but have distinct signaling
      properties. These experiments further indicate a previously unrecognized role for
      the extramembranous portion of the beta subunit in receptor signaling and
      internalization.

PMID- 7510689
TI  - Thrombin and thrombin receptor agonist peptide induce early events of T cell
      activation and synergize with TCR cross-linking for CD69 expression and
      interleukin 2 production.
AB  - Thrombin stimulation of the T leukemic cell line Jurkat induced a transient
      increase in [Ca2+]i. Proteolytic activity of the enzyme was required for this
      effect since diisopropyl fluorophosphate-thrombin failed to increase [Ca2+]i.
      Furthermore, hirudin and anti-thrombin III inhibited the thrombin-induced [Ca2+]i
      rise in Jurkat T cells. A synthetic thrombin receptor agonist peptide (TRP) of 7
      residues (SFLLRNP) was found to be as effective as thrombin for [Ca2+]i
      mobilization, and both agonists induced Ca2+ release exclusively from internal
      stores. Thrombin stimulated tyrosine phosphorylation of several proteins of
      molecular mass 40, 42, 70, 120, and 130 kDa. There was a good correlation between
      thrombin-induced tyrosine phosphorylation of the latter three proteins and Ca2+
      mobilization. Thrombin and TRP also caused translocation of protein kinase C from
      the cytosol to the plasma membrane. As a likely consequence of these events,
      thrombin activated the nuclear factor NF-kB. Several cell lines of hematopoietic
      origin including the leukemic T cell line HPB.ALL and the erythroleukemic cell
      line K562 were responsive to thrombin, whereas others such as THP1, a
      myelomonocytic cell line, and BL2, a Burkitt lymphoma were refractory to thrombin
      or TRP stimulation. The magnitude of the thrombin response in the different cell
      types paralleled the expression of the thrombin receptor mRNA. We found that
      activation of Jurkat T cells by a combination of phytohemagglutinin and phorbol
      12-myristate 13-acetate led to a dramatic inhibition of thrombin receptor mRNA
      expression and to a concomitant loss of the thrombin response. Finally, we
      demonstrate that thrombin and TRP enhanced CD69 expression and interleukin 2
      production induced by T cell receptor cross-linking in both Jurkat T cells and
      peripheral blood lymphocytes. These findings highlight the role of thrombin as a
      potential regulator of T lymphocyte activation.

PMID- 7510690
TI  - Alternative modes of polymerization distinguish the subunits of equine infectious
      anemia virus reverse transcriptase.
AB  - A comparative study of recombinant 51- and 66-kDa subunits comprising equine
      infectious anemia virus reverse transcriptase (EIAV RT) is reported. Both
      polypeptides sedimented as stable homodimers (molecular mass, 102 and 132 kDa,
      respectively) when analyzed by rate sedimentation through glycerol gradients.
      Consistent with their dimer composition, each preparation displayed considerable
      levels of both RNA- and DNA-dependent DNA polymerase activity on different
      homopolymeric template/primer combinations. However, a detailed analysis of the
      polymerization products indicated qualitative differences. Whereas p66 EIAV RT
      proceeded essentially unimpaired along both RNA and DNA templates, p51-catalyzed
      DNA synthesis was interrupted close to or in the immediate vicinity of the
      primer. A series of "programmed" 2-step polymerization reactions suggests that
      p51 EIAV RT enters an abortive mode of polymerization. Duplication of this
      observation with p51 human immunodeficiency virus-1 RT, together with recent
      observations from murine RT, suggests that lack of a ribonuclease H domain and
      loss of contact with the nascent product from the polymerase active center have
      profound consequences on the mode of polymerization.

PMID- 7510691
TI  - The interleukin-8 AP-1 and kappa B-like sites are genetic end targets of FK506
      sensitive pathway accompanied by calcium mobilization.
AB  - FK506, an immunosuppressant, inhibits the production of several cytokines in T
      lymphocytes. We observed that FK506 suppressed the transcription of a chemotactic
      cytokine, interleukin-8 (IL-8) in a human T cell line, Jurkat cells, activated by
      phorbol 12-myristate 13-acetate (PMA) and calcium (Ca2+) ionophore (ionomycin).
      By deleted and mutated analysis of the IL-8 promoters, the AP-1 and kappa B-like
      sites were identified as the responsive elements for PMA and ionomycin. FK506
      suppressed the transcriptions through the AP-1 or kappa B-like sites induced by
      PMA plus Ca(2+)-mobilizing agents, but not those induced by Ca(2+)-independent
      stimuli. In gel retardation analysis, FK506 had little effect on the binding to
      the AP-1 site of PMA/ionomycin-induced nuclear factors, which were recognized
      with anti-JunD or c-Fos antibody. In contrast, FK506 or EGTA (Ca2+ chelator)
      similarly affected the formation of kappa B-like site binding complexes, which
      were not recognized by any antibodies against the human Rel family proteins (c
      Rel, p65, p50, and p49). Furthermore, we confirmed the previous report that FK506
      suppressed the PMA/ionomycin-induced activation through authentic kappa B site of
      immunoglobulin (Ig) gene, to which NF-kappa B binding was also decreased by
      FK506, indicating that both IL-8 kappa B-like site and Ig kappa B site are FK506
      sensitive in spite of the difference of binding factors. Our results indicate
      that not only the reported IL-2 NF-AT and NFIL-2A sites and Ig kappa B site, but
      also the IL-8 AP-1 and kappa B-like sites are terminals of FK506-sensitive
      pathway involving Ca2+ mobilization.

PMID- 7510692
TI  - A delayed-early gene activated by fibroblast growth factor-1 encodes a protein
      related to aldose reductase.
AB  - The addition of polypeptide mitogens to quiescent cell lines induces the
      expression of various gene products, some of which are likely to perform
      functions critical for cell cycle progression, DNA synthesis, and mitosis. We
      have used a differential display approach to identify fibroblast growth factor
      (FGF)-1-inducible genes in NIH-3T3 cells. One of these genes, termed FGF
      regulated (FR)-1, encodes a 316-amino acid protein with approximately 82% amino
      acid sequence identity to an abundant protein expressed in mouse vas deferens and
      approximately 70% identity to human aldose reductase. The function of the vas
      deferens protein is unknown; however, aldose reductase is an NADPH-dependent
      monomeric oxidoreductase implicated in the pathogenesis of diabetic
      complications. FGF-1 induction of FR-1 mRNA expression is first detectable at 4 h
      after mitogen addition and is dependent on de novo RNA and protein synthesis. FGF
      2 or phorbol ester treatment can also increase FR-1 mRNA levels; in contrast,
      whole blood serum or individual growth factors present in serum have only minimal
      effects on FR-1 mRNA expression. FR-1 mRNA is detectable in a number of mouse
      tissues but is most abundant in newborn liver and in adult intestine, ovary, and
      testis. These results raise the possibility that aldose reductase-related
      proteins may play a role in FGF-1- and FGF-2-stimulated mitogenesis.

PMID- 7510693
TI  - Elimination of a major inhibitor epitope in factor VIII.
AB  - The A2 and C2 domains of human blood coagulation factor VIII (fVIII) contain the
      epitopes targeted by most inhibitory allo- and autoantibodies. Human inhibitors
      usually display limited or no reaction with porcine fVIII. We constructed an
      active, recombinant hybrid human/porcine fVIII molecule by replacing the putative
      human fVIII A2 domain epitope with the homologous porcine sequence. The hybrid
      retained full activity in the presence of antibodies with specificity restricted
      to the human A2 epitope. In contrast, the hybrid was neutralized by an anti-C2
      antibody. These findings provide a basis for fine epitope mapping and for therapy
      of the inhibitor patient.

PMID- 7510694
TI  - The carboxyl-terminal domain of lipoprotein lipase binds to the low density
      lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) and
      mediates binding of normal very low density lipoproteins to LRP.
AB  - Lipoprotein lipase (LPL) binds with high affinity to the low density lipoprotein
      receptor-related protein/alpha 2-macroglobulin receptor (LRP) and promotes
      binding, uptake, and degradation of normal triglyceride-rich lipoproteins in a
      process mediated by LRP (Chappell, D. A., Fry, G. L., Naknitx, M.A., Muhonen, L.
      E., Pladet, M. W., Iverius, P-H., and Strickland, D. K. (1993) J. Biol. Chem.
      268, 14168-14175). To localize the portion of LPL that is responsible for
      interacting with LRP, fragments of LPL were expressed in bacteria. A fragment of
      human LPL containing the COOH-terminal domain (residues 313-448, designated LPLC)
      which lacks the catalytic site was able to bind to LRP. Purified LRP bound
      specifically to microtiter wells coated with LPL or LPLC with KD values of 2.8
      and 5 nM, respectively. The effects of several mutations of LPLC were tested.
      Mutation of Lys407 to Ala reduced the affinity of LPLC for LRP by approximately
      10-fold. Like native LPL, LPLC prevented the binding of activated alpha 2
      macroglobulin and the 39-kDa receptor-associated protein to LRP and inhibited the
      internalization and degradation of activated alpha 2-macroglobulin and receptor
      associated protein in cultured fibroblasts. LPLC also bound to 125I-labeled human
      normal triglyceride-rich lipoproteins and promoted their binding to purified LRP
      and to cultured cells. Mutation of Trp393 and Trp394 to Ala completely abolished
      the ability of LPLC to bind to lipoproteins, but had little effect on its
      interaction with LRP. These data indicate that the COOH-terminal domain of LPL
      may function both in binding lipoproteins and mediating their interaction with
      LRP.

PMID- 7510696
TI  - Protein kinase A regulation of cAMP phosphodiesterase expression in rat skeletal
      myoblasts.
AB  - We have been studying cAMP signaling in L6 myoblasts because of its potential
      role in regulating the differentiation of these cells into multinucleate
      myotubes. Previous studies have shown that treatment of L6 myoblasts with cAMP
      analogs causes an increase in cAMP phosphodiesterase activity. To assess the role
      of protein kinase A in this cAMP-mediated increase in cAMP phosphodiesterase
      activity, L6 myoblasts were transfected with a plasmid containing the cDNA for a
      mutant regulatory subunit of protein kinase A, which functions as a dominant
      negative inhibitor of this enzyme. The cDNA was under control of the
      metallothionein promoter in the construct. Induction of the mutant regulatory
      subunit with Zn2+ decreased cAMP-dependent protein kinase activity by 90%. Zn2+
      treatment was also able to completely block the cAMP-mediated increase in
      phosphodiesterase activity, showing that this effect is mediated by protein
      kinase A. The activity of the cAMP-induced phosphodiesterase was inhibited by low
      concentrations of RO 20-1724, showing that it was a member of the type IV low Km
      cAMP phosphodiesterase family of enzymes. We used the polymerase chain reaction
      and consensus primers designed to amplify phosphodiesterase sequences to show
      that L6 myoblasts also contain mRNA for a type IV low Km cAMP phosphodiesterase
      designated PDE3.1. The levels of this mRNA were increased greatly by treatment
      with dibutyryl cAMP or forskolin in L6 myoblasts and also in differentiated L6
      myotubes. Run-off transcription assays showed that this increase in PDE mRNA was
      regulated, at least in part, by an increase in the rate of transcription of the
      PDE3 gene. The induction of PDE3 message by cAMP was blocked when the L6
      transfectants were treated with Zn2+ to induce protein kinase A inhibition.
      Therefore, some of the cAMP-mediated increase in phosphodiesterase activity seen
      in L6 myoblasts is due to a protein kinase A-mediated increase in PDE3 mRNA. This
      pathway may serve as a feedback mechanism to modulate the inhibitory effects of
      cAMP on myogenesis.

PMID- 7510695
TI  - Pyridine nucleotide redox potential modulates cystic fibrosis transmembrane
      conductance regulator Cl- conductance.
AB  - Cl- conductance of the apical membrane of airway epithelial cells has properties
      of a passive diffusion mechanism but is decreased by inhibition of oxidative
      metabolism. Recent reports that cAMP-dependent Cl- conductance also requires ATP
      at the intracellular domains of the cystic fibrosis transmembrane conductance
      regulator (CFTR) suggests that ATP concentration could mediate metabolic
      regulation of Cl- conductance. However, metabolic inhibitors affect processes
      other than ATP free energy levels, including notably the metabolic pathways that
      set the redox potential of pyridine nucleotides within the cell. We have
      investigated the possibility that CFTR-mediated Cl- conductance is affected by
      the ratio of oxidized to reduced intracellular pyridine nucleotides. CFTR was
      expressed in airway and heterologous cells and studied under whole cell voltage
      clamp conditions, which permitted the intracellular NAD(P)+/NAD(P)H ratio to be
      varied independently of ATP concentration. In three cell types expressing CFTR,
      whole cell dialysis with reduced pyridine nucleotides inhibited activation of Cl-
      currents by forskolin and 8-(4-chlorophenylthio)-cAMP (CPT-cAMP), whereas
      dialysis with oxidized pyridines increased both basal and stimulated CFTR
      mediated Cl- conductance. In cell-attached membrane patches, the open probability
      of 5-6-picosiemens Cl- channels that had been activated by forskolin and CPT-cAMP
      was further and reversibly increased by permeant oxidants. Neither swelling
      induced whole cell K+ currents in CFTR-expressing cells nor swelling-induced
      whole cell Cl- currents in multidrug resistance protein-expressing cells were
      affected by NADPH. Pyridine nucleotide redox potential had little effect on
      phosphorylation of histone by protein kinase A. We conclude that CFTR Cl-
      conductance function can be modulated by pyridine nucleotide redox potential.
      This effect points to the existence of a mechanism or mechanisms by which
      cytosolic nucleotides other than ATP can affect plasma membrane Cl- conductance
      and may help explain how a passive ion conductance is linked to cellular energy
      metabolism.

PMID- 7510698
TI  - A cell-surface proteoglycan mediates human adenocarcinoma HT-29 cell adhesion to
      human angiogenin.
AB  - Human angiogenin is an excellent substrate for the adhesion of HT-29 human colon
      adenocarcinoma cells. These cells adhere more quickly to human angiogenin than to
      fibronectin, laminin, collagen I, and collagen IV. Anti-angiogenin antibodies and
      the angiogenesis inhibitors platelet factor-4 and placental ribonuclease
      inhibitor prevent adhesion of HT-29 cells to angiogenin. Calcium and magnesium
      ions are not required for adhesion and Arg-Gly-Asp-Ser has no effect, indicating
      that the interaction is integrin-independent. Instead, adhesion seems to involve
      a heparan/chondroitin sulfate proteoglycan. Treatment of the cells with
      heparinase or heparitinase decreases HT-29 cell adhesion onto angiogenin but not
      onto collagen I. Moreover, cell adhesion is decreased by the presence of heparin
      or chondroitin sulfates and by preincubation of the cells with inhibitors of
      proteoglycan synthesis or secretion. In addition, angiogenin binds tightly to
      heparin-Sepharose, requiring 0.78 M NaCl for elution. Angiogenin-affinity
      chromatography of a 35S-, 3H-labeled HT-29 cell fraction enriched in cell-surface
      proteoglycans yields a single, heparinase-sensitive component of apparent
      molecular mass > 200 kDa, as detected by autoradiography after SDS-polyacrylamide
      gel electrophoresis. These results suggest that angiogenin could be an effective
      substrate for tumor cell adhesion during metastasis and may provide a basis for
      the design of inhibitors of this process.

PMID- 7510697
TI  - A Trk nerve growth factor (NGF) receptor point mutation affecting interaction
      with phospholipase C-gamma 1 abolishes NGF-promoted peripherin induction but not
      neurite outgrowth.
AB  - We analyzed the function of Trk nerve growth factor (NGF) receptors containing a
      point mutation (Tyr-->Phe) in a major autophosphorylation site (Tyr-785). Tyr-785
      is required for phospholipase C-gamma 1 to interact with Trk and to become
      tyrosine-phosphorylated in response to NGF. The altered receptors were
      transfected into a mutant subline of PC12 rat pheochromocytoma cells (designated
      PC12nnr5) that, unlike wild-type PC12 cells, lack expression of endogenous Trk
      and responsiveness to NGF. PC12nnr5 cells permanently transfected with Trk Y785F
      exhibit NGF-dependent autophosphorylation and normal NGF binding and
      internalization. Moreover, Trk Y785F mediates NGF-stimulated neurite outgrowth as
      well as a variety of additional responses including induction of immediate-early
      and late genes. However, in contrast to cells expressing wild-type Trk, cells
      expressing Trk Y785F lack NGF-promoted elevation of peripherin intermediate
      filament mRNA and protein. These observations indicate that phospholipase C-gamma
      1 activation or other signaling pathways dependent on Tyr-785 autophosphorylation
      are selectively required for regulation of peripherin expression by NGF, but not
      for many other functional NGF responses. This supports the presence of multiple
      and separable signaling pathways in the NGF mechanism of action.

PMID- 7510699
TI  - Cytosolic Ca2+ transients are not required for platelet-derived growth factor to
      induce cell cycle progression of vascular smooth muscle cells in primary culture.
      Actions of tyrosine kinase.
AB  - We investigated interrelations among changes in cytosolic Ca2+ concentrations
      ([Ca2+]i), tyrosine phosphorylation, and the cell cycles of rat aorta smooth
      muscle cells in primary culture, as stimulated with platelet-derived growth
      factor (PDGF). Changes in [Ca2+]i were monitored using the microfluorometry of
      Fura-2. The phase of the cell cycle and the extent of tyrosine phosphorylation
      were examined by immunocytochemical analysis of monoclonal antibodies against
      cell cycle-specific nuclear antigens and against phosphotyrosine, respectively.
      Prior to the application of PDGF, the cell cycle was synchronized in the G0 phase
      by serum deprivation for 24 h. In the presence of extracellular Ca2+, PDGF
      induced an initial transient (first component) and a subsequent lower steady
      state (second component) elevation of [Ca2+]i. NiCl2 and the removal of
      extracellular Ca2+ inhibited the second, but not the first, component. The first
      component was inhibited by pretreatment with ryanodine. These results are
      compatible with the notion that the first and second components may be mediated
      mainly through the release of intracellular Ca2+ and the influx of extracellular
      Ca2+, respectively. After pretreatment with ryanodine and in the presence of
      NiCl2, PDGF also stimulated the entry of G0 cells into G1 phase, but there were
      no [Ca2+]i transients. Genistein, a tyrosine kinase blocker, inhibited tyrosine
      phosphorylation induced by PDGF and blocked the first, but not the second,
      component of [Ca2+]i elevation induced by PDGF. However, genistein did not
      inhibit the release of intracellular Ca2+ induced by angiotensin II or by
      caffeine. Genistein prevented G0 cells from entering the G1 phase, as induced by
      PDGF, but this was not the case when serum was reapplied to the growth medium.
      Similar results were obtained with another tyrosine kinase blocker, tyrphostin.
      These data suggest that in vascular smooth muscle cells: 1) an increase in
      [Ca2+]i is not required for competent (G0 to G1) cell proliferation induced by
      PDGF; and 2) tyrosine kinase plays an important role in the release of
      intracellular Ca2+ and in cell proliferation, as induced by PDGF.

PMID- 7510700
TI  - A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane
      bound tyrosine phosphoprotein is implicated in ras activation in T cells.
AB  - T lymphocytes contain both Grb2, an SH2 and SH3 domain containing adaptor
      protein, and Sos, a guanine nucleotide exchange factor for Ras.
      Immunoprecipitates of Sos from the lysates of T cells contain a 36-kDa protein
      which is phosphorylated on tyrosine residues in response to T cell receptor/CD3
      cross-linking. In vitro studies using different bacterially synthesized GST-Sos
      fusion proteins confirm the formation of complexes containing p36 and the proline
      rich COOH-terminal domain of Sos. The use of mutant GST-Grb2 proteins in which
      both SH3 domains have been mutationally inactivated shows that Grb2 binds to
      tyrosine phosphorylated p36 via its SH2 domain. In Jurkat cells phosphorylated
      p36 is localized exclusively in the particulate fraction. In addition, another
      SH2 domain-containing protein, p52Shc is tyrosine phosphorylated upon TCR.CD3
      cross-linking and associates with a 150-kDa phosphotyrosine containing protein.
      Taken together these data suggest that activation of Ras in T cells via the
      TCR.CD3 complex might be controlled, at least in part, by mechanisms similar to
      those found in fibroblasts, involving in this case formation of a complex of
      Grb2, Sos, and a membrane-bound tyrosine phosphoprotein of molecular mass 36-kDa.

PMID- 7510701
TI  - The carboxyl-terminal residues of Escherichia coli DNA topoisomerase III are
      involved in substrate binding.
AB  - The nucleic acid-binding domain of Escherichia coli DNA topoisomerase III (Topo
      III) has been identified using a selection procedure designed to isolate inactive
      Topo III polypeptides. Deletion of this binding domain, contained in the carboxyl
      terminus of Topo III, results in a drastic reduction in the ability of the enzyme
      to bind to single-stranded DNA and RNA substrates. Successive truncation of the
      enzyme within this region results in the gradual loss of nucleic acid binding
      activity and in a gradual change in the mechanism of Topo III-catalyzed
      relaxation of negatively supercoiled DNA. The reduction of nucleic acid binding
      activity of the truncated polypeptides does not result in a loss of cleavage site
      specificity for the enzyme, suggesting that other amino acids are involved in the
      positioning of the nucleic acid within the nicking/closing site of the
      topoisomerase.

PMID- 7510702
TI  - Ligand binding specificity of alternatively spliced CD44 isoforms. Recognition
      and binding of hyaluronan by CD44R1.
AB  - CD44 species of widely differing molecular mass have been identified on various
      normal and/or transformed cells. Recent studies have demonstrated that much of
      this heterogeneity is produced as a result of the alternative splicing of a
      series of 10 exons present within the CD44 gene generating a large number of CD44
      isoforms containing additional peptide sequences of varying length inserted into
      a single site within the extracellular domain of the molecule. At present, the
      effect of such insertions on the ligand binding specificity of CD44 remains
      unclear. CD44H, the major CD44 isoform expressed by most resting cell types, has
      been shown to function as a receptor for the glycosaminoglycan hyaluronan. In
      contrast, CD44E, the major isoform expressed by the colon carcinoma cell line
      HT29, which contains a 132-amino acid insert, is unable to recognize and bind
      this ligand. In the present study we demonstrate that CD44R1, an isoform isolated
      from the myelomonocytic cell line KG1a, that differs from CD44E by just 3 amino
      acid substitutions, is fully capable of mediating the attachment of transfected
      COS7 cells to hyaluronan-coated plastic. In order to confirm that such binding
      was directly mediated by the introduced CD44 species, chimeric proteins
      containing the entire extracellular domain of CD44H or CD44R1 fused in-frame to
      human bone/liver/kidney alkaline phosphatase were prepared and tested for their
      ability to bind hyaluronan-coated plastic. Both fusion proteins bound equally
      well to hyaluronan and in each case their attachment could be readily inhibited
      by monoclonal antibodies directed against the hyaluronan-binding domain of CD44.
      These data indicate that the 132-amino acid insert present within the
      extracellular domain of CD44R1 does not interfere with the hyaluronan binding
      function of the molecule. Since CD44E contains an identically sized insert but is
      unable to bind hyaluronan, it is likely that mutation of one or more of the 3
      amino acid residues that differ between CD44E and CD44R1 is responsible for the
      altered functional activity of this particular molecule.

PMID- 7510703
TI  - Electrotransjection of pp60v-src monoclonal antibody inhibits activation of
      phospholipase C in platelets. A new mechanism for platelet-activating factor
      responses.
AB  - Antibodies to pp60v-arc and phosphotyrosine were introduced into rabbit platelets
      using an electropermeabilization technique. The presence of these antibodies
      inside platelets was detected by flow cytometry. Platelet-activating factor (PAF)
      stimulated phospholipase C activity (inositol phosphate production) and
      aggregation were dramatically inhibited in platelets transjected with either of
      these antibodies. Incubation of these antibodies with intact cells (i.e.
      nonpermeabilized) or electrotransjection of several nonspecific antibodies/agents
      (e.g. goat anti-mouse IgG, mouse serum, human platelet glycoprotein Ib monoclonal
      antibody, and fetal calf serum) into platelets had no effect on the PAF
      responses. trpE (another isotype-matched control antibody of pp60v-src) and
      pp56lck polyclonal antibody (another src-related kinase not present in platelets)
      also had no effect on PAF-induced aggregation and inositol phosphate production
      in permeabilized platelets. This indicates that the effect of internalized pp60v
      src antibody is direct and specific in platelets. Stimulation of platelets by PAF
      increased the association and phosphorylation of both pp60c-src (60 kDa) and
      phospholipase C gamma 1 (145 kDa). This study provides the first evidence in
      platelets for a direct and specific involvement of pp60c-src in PAF-mediated
      phospholipase C activation and aggregation response.

PMID- 7510704
TI  - Dephosphorylation of the small heat shock protein Hsp27 in vivo by protein
      phosphatase 2A.
AB  - The phosphorylation of the Hsp27 complex is rapidly altered in MRC-5 cells when
      they are exposed to mitogens, cytokines, stress, or serine/threonine protein
      phosphatase inhibitors. Here we performed experiments to identify which cellular
      protein phosphatase (PP1, PP2A, or PP2B) is responsible for the in vivo
      phosphorylation/dephosphorylation of Hsp27. In their purified forms, PP2A
      dephosphorylates Hsp27 more effectively than PP2B, whereas PP1 is weakly active.
      Measurements of enzyme activity of lysates derived from inhibitor-treated cells
      indicated that Hsp27 phosphatase activity is equally sensitive to okadaic acid
      (PPI/PP2A inhibitor) and cyclosporin (PP2B inhibitor) and that both okadaic acid
      and cyclosporin treatment inhibited Hsp27 phosphatase activity additively.
      Together the in vitro data suggest that both PP2A and PP2B can dephosphorylate
      Hsp27. However, the phosphorylation of Hsp27 in vivo is only affected when cells
      are treated with PP1 and PP2A inhibitors (okadaic acid, calyculin A) or
      cantharidin (PP2A inhibitor), but not the PP2B inhibitor, cyclosporin A,
      suggesting PP2A to be the main enzyme dephosphorylating Hsp27 in the cells.
      Purification and immunoblotting of Hsp27 phosphatase from MRC-5 cells also
      suggest it to be PP2A and not PP1 or PP2B. The ability of PP2A to dephosphorylate
      Hsp27 is shown to be regulated by the phosphorylation state of PP2A itself.

PMID- 7510705
TI  - Basic fibroblast growth factor-induced low density lipoprotein receptor
      transcription and surface expression. Signal transduction pathways mediated by
      the bFGF receptor tyrosine kinase.
AB  - Basic fibroblast growth factor (bFGF) has been implicated in the regulation of
      cell proliferation and cholesterol metabolism. In studies reported herein, we
      show bFGF increases low density lipoprotein (LDL) binding, uptake, and
      degradation in arterial smooth muscle cells in a dose-dependent manner. This
      increase was paralleled by an increase in LDL receptor mRNA steady state levels.
      To determine if bFGF activated transcription of the LDL receptor gene, we
      transiently transfected smooth muscle cells with a gene construct consisting of
      the 5'-upstream promoter region of the DNA from the human LDL receptor gene
      ligated to a plasmid containing the luciferase gene. We found that bFGF and a
      protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate, significantly
      induced luciferase activity driven by the LDL receptor promoter, whereas 25
      hydroxycholesterol reduced the luciferase activity in bFGF-stimulated cells.
      These findings show that bFGF and PKC are inducing LDL receptor gene
      transcription. We also evaluated potential signal transduction pathways induced
      by bFGF to establish the mechanism(s) leading to the activation of the LDL
      receptor gene. Activation of the activity of FGF receptor tyrosine kinase in
      smooth muscle cells by ligand binding resulted in tyrosine phosphorylation of one
      of the FGF receptors and a 90-kDa-protein as well as increased tyrosine
      phosphorylation of phospholipase C-gamma. Parallel observations were made in that
      increased PKC and protein kinase A activities occurred with bFGF as compared with
      control cells. Inhibitors of receptor tyrosine kinase and other protein kinases
      significantly reduced transcription and surface expression of LDL receptor.
      Finally, several key enzymes that are central to the regulation of LDL
      cholesteryl ester metabolism were also studied in bFGF-stimulated cells. An
      increase in acyl-CoA:cholesterol acyltransferase activity and cholesterol
      esterification was observed with bFGF stimulation, but there was no effect on the
      lysosomal or cytoplasmic cholesteryl ester hydrolase activities. Our findings
      suggest potential signal transduction pathways activated by bFGF which play a
      role in regulating transcription and surface expression of the LDL receptor.

PMID- 7510706
TI  - Phosphorylation of the tumor suppressor protein p53 by mitogen-activated protein
      kinases.
AB  - The p53 tumor suppressor protein is tightly regulated in the cell and is
      phosphorylated at multiple sites by several different protein kinases. We have
      investigated the phosphorylation of p53 by mitogen-activated protein (MAP)
      kinase, a protein kinase that plays a central role in mediating many mitogenic
      and differentiation signals. Recombinant wild-type mouse p53 was phosphorylated
      in vitro by activated recombinant p42-MAP kinase but not by inactive MAP kinase
      or by the activating protein, MAP kinase kinase. Phosphorylation of p53 by MAP
      kinase occurred at two N-terminal sites, threonine residues 73 and 83. Tryptic
      phosphopeptides of recombinant p53 phosphorylated in vitro by MAP kinase
      comigrated on two-dimensional maps with p53 from SV3T3 cells labeled in vivo with
      [32P]orthophosphate, suggesting that MAP kinase targets a site in p53 that is
      phosphorylated in the cell. Following serum stimulation of quiescent C57MG cells,
      two p53 kinases, which were resolved by chromatography on Mono Q, were stimulated
      15-20-fold within 5 min. Each of these kinase activities co-eluted with myelin
      basic protein kinase activity and could be inactivated following treatment with
      protein phosphatase 2A, a serine/threonine phosphatase, or leukocyte antigen
      receptor, a protein tyrosine phosphatase, suggesting that these activities were
      members of the MAP kinase family. The two kinase activities from the lysates
      targeted the same phosphorylation sites on p53 as the purified recombinant MAP
      kinase. These protein kinase activities were also stimulated following exposure
      of the cells to ultraviolet radiation, but with slightly delayed kinetics.
      Phorbol ester treatment of SV3T3 cells led to increased phosphorylation of the
      peptide containing the residues targeted by MAP kinase. The data suggest that p53
      may be phosphorylated by MAP kinase physiologically and that this interaction may
      be involved in the cell's response to UV exposure, growth factor stimulation, or
      transformation by oncogenes.

PMID- 7510707
TI  - Expression of laminin chains during myogenic differentiation.
AB  - Expression of two Ae-related chains of the extracellular matrix glycoprotein
      laminin was induced as multipotent C3H10T1/2 mouse embryo fibroblasts
      differentiated into myoblasts and myofibers. C3H10T1/2 fibroblasts expressed the
      B1e (M(r) = 215,000) and B2e (M(r) = 205,000) laminin chains based on metabolic
      radiolabeling, immunoprecipitation, peptide mapping, and mRNA analysis. In
      contrast, myoblasts derived from C3H10T1/2 fibroblasts treated with DNA
      demethylating agents or transfected with the cDNA encoding MyoD expressed the Ae
      (M(r) = 400,000) and a novel Ae-related laminin chain (designated Ac3h, M(r) =
      350,000) in addition to the B1e and B2e chains. Expression of the Ae and Ac3h
      chains paralleled the capacity for myofiber formation in six additional C3H10T1/2
      myoblast clones with varied potentials for terminal differentiation and coincided
      with a switch in laminin isoforms from those of M(r) = 850,000 synthesized by
      C3H10T1/2 fibroblasts to those of M(r) = 900,000-950,000 synthesized by C3H10T1/2
      myoblasts and myofibers. Cultures of mouse C2C12, mouse BC3H1, rat L6, and
      primary mouse myoblasts also synthesized the Ae, Ac3h, B1e, and B2e laminin
      chains. The results demonstrate that expression of the Ae and Ac3h laminin chains
      is associated with expression of MyoD and the mammalian myogenic differentiation
      program.

PMID- 7510708
TI  - Lysophosphatidic acid stimulates tyrosine phosphorylation of focal adhesion
      kinase, paxillin, and p130. Signaling pathways and cross-talk with platelet
      derived growth factor.
AB  - Addition of 1-oleoyl-lysophosphatidic acid (LPA) induces tyrosine phosphorylation
      of multiple substrates in Swiss 3T3 cells including bands of M(r) 110,000-130,000
      and M(r) 70,000-80,000. An increase in tyrosine phosphorylation of the M(r)
      110,000-130,000 cluster of bands was detected as soon as 30 s after LPA
      stimulation reaching a maximum within 1 min. LPA stimulated tyrosine
      phosphorylation of all bands in a concentration-dependent fashion; a half-maximal
      effect occurred at 30 nM. Immunoprecipitation of lysates of LPA-treated cells
      with monoclonal antibodies that specifically recognize focal adhesion kinase
      (p125FAK), paxillin, and p130 revealed that these proteins are prominent
      substrates for LPA-stimulated tyrosine phosphorylation. Down-regulation of
      protein kinase C (PKC) by prolonged pretreatment with phorbol 12,13-dibutyrate,
      selective inhibition of PKC by GF109203X, or depletion of the intracellular Ca2+
      pool by thapsigargin had no effect on LPA-stimulated tyrosine phosphorylation.
      Thus, protein tyrosine phosphorylation by LPA is largely independent of either
      the PKC or Ca2+ pathways. In contrast, pretreatment of the cells with
      cytochalasin D, which selectively disrupts the network of the actin filaments,
      completely inhibited LPA-induced tyrosine phosphorylation. Furthermore, tyrosine
      phosphorylation of p125FAK induced by LPA was completely prevented when cells
      were stimulated in the presence of platelet-derived growth factor at a
      concentration (30 ng/ml) that causes disruption of actin stress fibers. This
      suggests that the integrity of the actin cytoskeleton is essential for LPA
      induced tyrosine phosphorylation and reveals a novel cross-talk between LPA and
      platelet-derived growth factor on p125FAK tyrosine phosphorylation.

PMID- 7510709
TI  - Identification of the phosphorylation site for cAMP-dependent protein kinase on
      Na+,K(+)-ATPase and effects of site-directed mutagenesis.
AB  - Phosphorylation of purified Na+,K(+)-ATPase by cAMP-dependent protein kinase
      (protein kinase A) decreases the activity of this enzyme. We have now shown,
      using several experimental approaches, that a highly conserved seryl residue on
      the catalytic (alpha) subunit of Na+,K(+)-ATPase, corresponding to Ser943 of the
      rat alpha 1 isoform, is the phosphorylation site for protein kinase A. cDNAs
      corresponding to wild-type Na+,K(+)-ATPase and Na+,K(+)-ATPase in which Ser943
      was mutated to Ala were transfected into COS cells. Treatment of the transfected
      cells with forskolin plus 3-isobutyl-1-methylxanthine resulted in a decrease in
      the activity of the wild-type enzyme but not in that of the mutated enzyme. The
      results suggest that, in intact cells, the activity of the Na+,K(+)-ATPase is
      regulated in part by signal transduction pathways that use protein kinase A
      dependent phosphorylation of the Na+,K(+)-ATPase alpha subunit.

PMID- 7510710
TI  - Growth-inhibitory effects of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin on
      human malignant cell lines in vitro.
AB  - Coumarin (1,2-benzopyrone) is a natural substance that has shown antitumor
      activity in vivo. The major human metabolite of coumarin, 7-hydroxycoumarin (7
      HC), is the active form of the drug. While the exact mechanism(s) of action of
      coumarin is unknown, it has been shown previously that this drug possesses
      immunomodulatory activity in vitro and in vivo. The present investigations
      examined the direct (non-immunological) antitumor effects of coumarin and 7-HC in
      vitro. Both coumarin and 7-HC were found to be growth-inhibitory (cytostatic) for
      the following human malignant cell lines: A549, ACHN, Caki-2, Dakiki, HS-Sultan,
      H727, HCT-15, HL-60, K562, LNCaP, PC-3, Du 145 COLO-232, MCF-7 and RP-1788. The
      growth inhibition was dependent on dose and time and was reversible upon removal
      of cells from medium containing the drug. Coumarin and 7-HC inhibited
      [3H]thymidine, [3H]uridine and [3H]leucine incorporation. In a similar fashion,
      coumarin and 7-HC inhibited the intracellular production of prostate-specific
      antigen by LNCaP cells. Coumarin and 7-HC stimulated apoptosis in HL-60 cells but
      not in other cell lines tested. It is concluded that coumarin and 7-HC have
      direct antitumor (cytostatic) activity as well as immunomodulatory activity.
      Further information is needed in order to determine which activities are
      responsible for antitumor activity in vivo.

PMID- 7510711
TI  - Expression of a beta 1-related integrin by oligodendroglia in primary culture:
      evidence for a functional role in myelination.
AB  - We have investigated the expression of integrins by rat oligodendroglia grown in
      primary culture and the functional role of these proteins in myelinogenesis.
      Immunochemical analysis, using antibodies to a number of alpha and beta integrin
      subunits, revealed that oligodendrocytes express only one detectable integrin
      receptor complex (alpha OL beta OL). This complex is immunoprecipitated by a
      polyclonal anti-human beta 1 integrin subunit antibody. In contrast, astrocytes,
      the other major glial cell type in brain, express multiple integrins including
      alpha 1 beta 1, alpha 3 beta 1, and alpha 5 beta 1 complexes that are
      immunologically and electrophoretically indistinguishable from integrins
      expressed by rat fibroblasts. The beta subunit of the oligodendrocyte integrin
      (beta OL) and rat fibroblast beta 1 have different electrophoretic mobilities in
      SDS-PAGE. However, the two beta subunits appear to be highly related based on
      immunological cross-reactivity and one-dimensional peptide mapping. After removal
      of N-linked carbohydrate chains, beta OL and beta 1 comigrated in SDS-PAGE and
      peptide maps of the two deglycosylated subunits were identical, suggesting
      differential glycosylation of beta 1 and beta OL accounts entirely for their size
      differences. The oligodendrocyte alpha subunit, alpha OL, was not
      immunoprecipitated by antibodies against well characterized alpha chains which
      are known to associate with beta 1 (alpha 3, alpha 4, and alpha 5). However, an
      antibody to alpha 8, a more recently identified integrin subunit, did precipitate
      two integrin subunits with electrophoretic mobilities in SDS-PAGE identical to
      alpha OL and beta OL. Functional studies indicated that disruption of
      oligodendrocyte adhesion to a glial-derived matrix by an RGD-containing synthetic
      peptide resulted in a substantial decrease in the level of mRNAs for several
      myelin components including myelin basic protein (MBP), proteolipid protein
      (PLP), and cyclic nucleotide phosphodiesterase (CNP). These results suggest that
      integrin-mediated adhesion of oligodendrocytes may trigger signal(s) that induce
      the expression of myelin genes and thus influence oligodendrocyte
      differentiation.

PMID- 7510713
TI  - Extracellular Ca2+ modulates leukocyte function-associated antigen-1 cell surface
      distribution on T lymphocytes and consequently affects cell adhesion.
AB  - Transition of leukocyte function-associated antigen-1 (LFA-1), from an inactive
      into an activate state depends on the presence of extracellular Mg2+ and/or Ca2+
      ions. Although Mg2+ is directly involved in ligand binding, the role of Ca2+ in
      LFA-1 mediated adhesion remained obscure. We now demonstrate that binding of
      Ca2+, but not Mg2+, directly correlates with clustering of LFA-1 molecules at the
      cell surface of T cells, thereby facilitating LFA-1-ligand interaction. Using a
      reporter antibody (NKI-L16) that recognizes a Ca(2+)-dependent epitope on LFA-1,
      we found that Ca2+ can be bound by LFA-1 with different strength. We noticed that
      weak binding of Ca2+ is associated with a dispersed LFA-1 surface distribution on
      T cells and with non-responsiveness of these cells to stimuli known to activate
      LFA-1. In contrast, stable binding of Ca2+ by LFA-1 correlates with a patch-like
      surface distribution and vivid ligand binding after activation of LFA-1. Mg(2+)
      dependent ligand binding does not affect binding of Ca2+ by LFA-1 as measured by
      NKI-L16 expression, suggesting that Mg2+ binds to a distinct site, and that both
      cations are important to mediate adhesion. Only Sr2+ ions can replace Ca2+ to
      express the L16 epitope, and to induce clustering of LFA-1 at the cell surface.
      We conclude that Ca2+ is involved in avidity regulation of LFA-1 by clustering of
      LFA-1 molecules at the cell surface, whereas Mg2+ is important in regulation of
      the affinity of LFA-1 for its ligands.

PMID- 7510712
TI  - Integrin cytoplasmic domains mediate inside-out signal transduction.
AB  - We analyzed the binding of fibronectin to integrin alpha 5 beta 1 in various
      cells; in some cells fibronectin bound with low affinity (e.g., K562 cells)
      whereas in others (e.g., CHO), it bound with high affinity (Kd approximately 100
      nM) in an energy-dependent manner. We constructed chimeras of the extracellular
      and transmembrane domains of alpha IIb beta 3 joined to the cytoplasmic domains
      of alpha 5 beta 1. The affinity state of these chimeras was assessed by binding
      of fibrinogen or the monoclonal antibody, PAC1. The cytoplasmic domains of alpha
      5 beta 1 conferred an energy-dependent high affinity state on alpha IIb beta 3 in
      CHO but not K562 cells. Three additional alpha cytoplasmic domains (alpha 2,
      alpha 6A, alpha 6B) conferred PAC1 binding in CHO cells, while three others
      (alpha M, alpha L, alpha v) did not. In the high affinity alpha chimeras,
      cotransfection with a truncated (beta 3 delta 724) or mutated (beta 3(S752-->P))
      beta 3 subunit abolished high affinity binding. Thus, both cytoplasmic domains
      are required for energy-dependent, cell type-specific affinity modulation. In
      addition, mutations that disrupted a highly conserved alpha subunit GFFKR motif,
      resulted in high affinity binding of ligands to alpha IIb beta 3. In contrast to
      the chimeras, the high affinity state of these mutants was independent of
      cellular metabolism, cell type, and the bulk of the beta subunit cytoplasmic
      domain. Thus, integrin cytoplasmic domains mediate inside-out signaling.
      Furthermore, the highly conserved GFFKR motif of the alpha subunit cytoplasmic
      domain maintains the default low affinity state.

PMID- 7510715
TI  - Epitopes on the beta subunit of human muscle acetylcholine receptor recognized by
      CD4+ cells of myasthenia gravis patients and healthy subjects.
AB  - We investigated the sequence regions of the human muscle acetylcholine receptor
      (AChR) beta subunit forming epitopes recognized by T helper cells in myasthenia
      gravis (MG), using overlapping synthetic peptides, 20 residues long, which
      screened the sequence of the AChR beta subunit. Since CD4+ lymphocytes from MG
      patients' blood did not respond to the peptides, we attempted propagation of beta
      subunit-specific T lines from six MG patients and seven healthy controls by
      cycles of stimulation of blood lymphocytes with the pooled peptides corresponding
      to the beta subunit sequence. CD4+ T lines were obtained from four patients and
      three controls. They secreted IL-2, not IL-4, suggesting that they comprised T
      helper type 1 cells. The T lines from MG patients could be propagated for several
      months. Three lines were tested with purified bovine muscle AChR and cross
      reacted well with this antigen. All T lines were tested with the individual
      synthetic peptides present in the pool corresponding to the beta subunit
      sequence. Several beta subunit peptide sequences were recognized. Each line had
      an individual pattern of peptides recognition, but three sequence regions
      (peptides beta 181-200, beta 271-290, and the overlapping peptides beta 316-335
      and beta 331-350) were recognized by most MG lines. The beta subunit-specific T
      lines from controls could be propagated for < 5 wk. Each line recognized several
      peptides, which frequently included the immunodominant regions listed above.

PMID- 7510714
TI  - Subcellular partitioning of MRP RNA assessed by ultrastructural and biochemical
      analysis.
AB  - A small RNA encoded within the nucleus is an essential subunit of a RNA
      processing endonuclease (RNase MRP) hypothesized to generate primers for
      mitochondrial DNA replication from the heavy strand origin of replication.
      Controversy has arisen, however, concerning the authenticity of an
      intramitochondrial pool of MRP RNA, and has called into question the existence of
      pathways for nucleo-mitochondrial transport of nucleic acids in animal cells. In
      an effort to resolve this controversy, we combined ultrastructural in situ
      hybridization and biochemical techniques to assess the subcellular partitioning
      of MRP RNA. Cryosections of mouse cardiomyocytes were hybridized with biotin
      labeled RNA probes complementary to different regions of MRP RNA and varying in
      length from 115 to 230 nucleotides, followed by immunogold labeling. In addition,
      we transfected mouse C2C12 myogenic cells with constructs bearing mutated forms
      of the mouse MRP RNA gene and compared the relative abundance of the resulting
      transcripts to that of control RNAs within whole cell and mitochondrial
      fractions. In the former analysis we observed preferential localization of MRP
      RNA to nucleoli and mitochondria in comparison to the nucleoplasm and cytoplasm.
      In the latter series of studies we observed that wild-type MRP RNA partitions to
      the mitochondrial fraction by comparison to other RNA transcripts that are
      localized to the extramitochondrial cytoplasmic space (28S rRNA) or to the
      nucleoplasm (U1 snRNA). Deletions within 5' or 3' regions of the MRP RNA gene
      produced transcripts that remain competent for mitochondrial targeting. In
      contrast, deletion of the midportion of the coding region (nt 118 to 175) of the
      MRP RNA gene resulted in transcripts that fail to partition to the mitochondrial
      fraction. We conclude that an authentic intramitochondrial pool of MRP RNA is
      present in these actively respiring cells, and that specific structural
      determinants within the MRP RNA molecule permit it to be partitioned to
      mitochondria.

PMID- 7510716
TI  - The apoptosis-1/Fas protein in human systemic lupus erythematosus.
AB  - Three independent mutations involving the apoptosis-1 (APO-1)/Fas receptor or its
      putative ligand have led to lupuslike diseases associated with lymphadenopathy in
      different strains of mice. To determine whether humans with SLE also have a
      defect in this apotosis pathway, we analyzed the expression of APO-1 on freshly
      isolated blood mononuclear cells and on lymphocytes activated in vitro using flow
      cytometry and the monoclonal antibody anti-APO-1. Significantly higher level of
      APO-1 expression were detected on freshly isolated peripheral B cells and both
      CD4+ and CD8+ T lymphocyte populations obtained from lupus patients when compared
      with normal controls (P < 0.001). Almost 90% of the cells that stained positive
      for APO-1 also expressed the CD29 antigen, suggesting that APO-1 was upregulated
      after lymphocyte activation in vivo. No defect in APO-1 regulation was detected
      after activation of SLE T (with anti-CD3) or B (with Staphylococcus aureus Cowan
      1) lymphocytes in the presence of IL-2 in vitro. Similarly, the anti-APO-1
      antibody induced apoptosis in 74 +/- 5% of activated SLE T cells in vitro
      compared with 79 +/- 6% of the normal controls (P > 0.05). These results reveal
      that, while APO-1/Fas may play an important role in the regulation of lymphocyte
      survival in SLE, no consistent defect in the expression or function of the
      receptor could be detected in these studies.

PMID- 7510718
TI  - Cloning, characterization, and chromosomal mapping of human aquaporin of
      collecting duct.
AB  - We recently cloned a cDNA of the collecting duct apical membrane water channel of
      rat kidney, which is important for the formation of concentrated urine (Fushima,
      K., S. Uchida, Y. Hara, Y. Hirata, F. Marumo, and S. Sasaki. 1993. Nature
      [Lond.]. 361:549-552). Since urine concentrating ability varies among mammalian
      species, we examined whether an homologous protein is present in human kidney. By
      screening a human kidney cDNA library, we isolated a cDNA clone, designated human
      aquaporin of collecting duct (hAQP-CD), that encodes a 271-amino acid protein
      with 91% identity to rat AQP-CD. mRNA expression of hAQP-CD was predominant in
      the kidney medulla compared with the cortex, immunohistochemical staining of hAQP
      CD was observed only in the collecting duct cells, and the staining was dominant
      in the apical domain. Functional expression study in Xenopus oocytes confirmed
      that hAQP-CD worked as a water channel. Western blot analysis of human kidney
      medulla indicated that the molecular mass of hAQP-CD is 29 kD, which is the same
      mass expected from the amino acid sequence. Chromosomal mapping of the hAQP-CD
      gene assigned its location to chromosome 12q13. These results could be important
      for future studies of the pathophysiology of human urinary concentration
      mechanisms in normal and abnormal states.

PMID- 7510717
TI  - Regulation of the costimulator B7, not class II major histocompatibility complex,
      restricts the ability of murine kidney tubule cells to stimulate CD4+ T cells.
AB  - The proximal segment of murine kidney tubule cells (KTC) constitutively expresses
      low levels of class II major histocompatibility complex (MHC) that are
      upregulated during local and systemic inflammation. It is not known if KTC also
      express the costimulator molecules necessary for them to productively participate
      in immune responses and stimulate T cells. To answer this question, we studied
      the ability of KTC to present antigens to four Th1 clones. KTC did not induce T
      cell proliferation to specific antigen, superantigen, or concanavalin A. However,
      T cell receptors did engage the peptide/MHC ligand presented by KTC, as indicated
      by T cell enlargement and upregulation of interleukin-2 receptor expression.
      Importantly, KTC failed to express the Th1 costimulator, B7, as detected by
      fluorescence cytometry and reverse transcription polymerase chain reaction. We
      directly demonstrated that lack of B7 expression accounted for at least part of
      the KTC presentation defect, in that a KTC line transfected with the cDNA for B7
      stimulated T cell proliferation to antigen. Our results suggest that epithelial
      cells expressing class II MHC have developed mechanisms to prevent costimulator
      expression and limit parenchymal tissue destruction. Failure of class II
      expressing epithelial cells to limit costimulator expression may be an important
      component of organ-specific autoimmunity.

PMID- 7510719
TI  - A spoonful of sugar to control inflammation?

PMID- 7510721
TI  - Cytokeratin expression and acetowhite change in cervical epithelium.
AB  - AIM: To investigate the distribution of cytokeratins 10, 13, 14 and 19 in biopsy
      specimens taken from acetowhite and non-acetowhite areas of the cervix. METHOD:
      Cervical biopsy specimens were taken from both acetowhite and non-acetowhite
      areas from 44 patients who presented with abnormal cervical cytology. The
      specimens were snap frozen in liquid nitrogen and multiple sections taken from
      each specimen. Staining was performed for cytokeratins 10, 13, 14, 19 and NADPH
      diaphorase enzyme. The areas of each section positive for the various markers
      were measured. RESULTS: Cytokeratin 10 positive cells were greatly increased in
      number in acetowhite biopsy specimens compared with non-acetowhite samples (45.1%
      v 2.8%; p < 0.0001). Cytokeratin 19 was also increased, but to a lesser extent
      (17.8% v 5.5%; p < 0.0001). In contrast, the almost universal expression of
      cytokeratin 13 was reduced in acetowhite biopsy specimens (86.2% v 96.9%; p <
      0.0001). Cytokeratin 14 was found diffusely in the basal region of the stratified
      squamous epithelium and was marginally more apparent in the acetowhite biopsy
      specimens (p = 0.04). CONCLUSION: It is suggested that the presence of
      cytokeratin 10 may be an essential requirement for the formation of acetowhite
      change in association with the cellular swelling caused by acetic acid.

PMID- 7510722
TI  - Gram negative septicaemia diagnosed on peripheral blood smear appearances.
AB  - Buffy coat smears from febrile patients may contain visible bacteria and
      therefore detect bacteraemia before conventional blood cultures become positive.
      However, it is unusual to see micro-organisms in an otherwise untreated
      peripheral blood smear. The case of a febrile neutropenic patient is reported. A
      Wright's stained peripheral blood smear contained bacterial elements, thus making
      earlier diagnosis of septicaemia and identification of the causative bacterium
      possible.

PMID- 7510723
TI  - Multiblock slides: a useful technique for teaching.
AB  - Data on the quality of a modified method for producing multiblocks from
      conventional blocks of paraffin wax embedded histological material are reported.
      Originally devised as a way of assessing antibodies for immunohistology, the
      technique is particularly suited to producing a set of reference and teaching
      material for use by trainee and senior pathologists.

PMID- 7510720
TI  - Inhibition of leukocyte rolling with polysaccharide fucoidin prevents pleocytosis
      in experimental meningitis in the rabbit.
AB  - Inflammatory recruitment of leukocytes into the cerebrospinal fluid (CSF) during
      bacterial meningitis has been shown to contribute significantly to the
      neurological damage commonly associated with this serious disease. In this study
      we tested whether or not inhibition of leukocyte rolling, a precondition for firm
      leukocyte adhesion to vascular endothelium in vivo, may reduce CSF leukocyte
      recruitment and associated inflammatory changes in rabbits with experimental
      meningitis. As documented by intravital microscopy of small venules in the rabbit
      mesentery and tenuissimus muscle, leukocyte rolling was rapidly and profoundly
      reduced by intravenous treatment with the polysaccharide fucoidin, a homopolymer
      of sulfated L-fucose known to block the function of the leukocytic "rolling
      receptor" L-selectin. Moreover, fucoidin treatment dramatically reduced the
      accumulation of both leukocytes and plasma protein in the CSF of rabbits
      challenged intrathecally with pneumococcal antigen. These main findings thus
      illustrate that inhibition of leukocyte rolling, an early and obligatory step in
      the process of leukocyte extravasation, may be an effective therapeutic approach
      to attenuate leukocyte-dependent central nervous system damage in bacterial
      meningitis.

PMID- 7510725
TI  - Chronic liver disease and active hepatitis C virus infection in patients with
      antibodies to this virus.
AB  - AIMS: To assess the association between active hepatitis C virus (HCV) infection
      and liver damage in randomly selected patients with antibodies to the virus.
      METHODS: Thirty three consecutive subjects with serologically confirmed
      positivity for antibodies to HCV were studied for the presence of liver and
      circulating viral sequences by using the reverse transcription polymerase chain
      reaction (RT-PCR) and specific primers for the 5'-untranslated region (5'-UTR) of
      the HCV genome. Parallel clinical, biochemical, and histological investigations
      were carried out in all cases. RESULTS: A comparative virological and
      histological investigation showed the presence of molecular signs of active viral
      replication and different degrees of liver damage in all cases. Baseline values
      of liver and plasma samples from all the patients showed (with one exception) the
      presence of detectable HCV RNA sequences, despite alanine amino transferase
      activities being within normal values or within 1.5 times the upper limit of
      normal in 13 of them. Examination of percutaneous liver biopsy specimens showed
      the presence of confirmed liver damage (ranging from chronic persistent hepatitis
      to cirrhosis) in all 33 patients. CONCLUSIONS: Circulating HCV RNA sequences (a
      direct sign of active HCV infection) are associated with liver damage, even in
      the absence of clinical or biochemical signs of overt liver disease. Parallel
      molecular, histological, and clinical follow up of these patients is needed to
      understand precisely the natural history of HCV infection and for correct
      clinical management.

PMID- 7510727
TI  - Blue paraffin wax blocks: a solution to the problem.

PMID- 7510726
TI  - Monitoring the acute phase response to vaso-occlusive crisis in sickle cell
      disease.
AB  - AIMS: To identify suitable acute phase proteins as objective markers of tissue
      ischaemia during painful vaso-occlusive crises in sickle cell disease. METHODS:
      The prodromal and established phases of 14 vaso-occlusive crises were studied
      longitudinally in 10 patients with sickle cell anaemia. Automated solid phase
      enzyme immunoassays were used to measure the fast responding acute phase proteins
      C-reactive protein and serum amyloid A protein. Slower responding glycoproteins
      (fibrinogen, orosomucoid, sialic acid and concanavalin-A binding) were measured
      in parallel. RESULTS: C-reactive protein and serum amyloid A protein increased
      early in crisis, sometimes within the early (prodromal) phase. Crises that
      resolved within 24 hours in hospital showed a minor and transient rise compared
      with crises that required treatment for four days or more. In eight crises
      treated by patients at home the acute phase response ranged from minor to a level
      consistent with extensive tissue ischaemia. CONCLUSIONS: Sensitive enzyme
      immunoassays for C-reactive protein and serum amyloid A protein are of potential
      value for monitoring the onset of tissue ischaemia in sickle cell crisis and for
      confirming subsequent resolution.

PMID- 7510724
TI  - Lymph node hyalinisation in rheumatoid arthritis and systemic sclerosis.
AB  - AIMS: To review the histological features of lymph nodes excised from seven
      patients with rheumatoid arthritis and one with systemic sclerosis. METHODS:
      Lymph nodes excised from seven patients with rheumatoid arthritis and one patient
      with systemic sclerosis over a 10 year period were examined using the stains
      haematoxylin and eosin, periodic acid Schiff (PAS), Masson-trichrome, and Congo
      red for amyloid. RESULTS: Of the seven nodes examined from the cases of
      rheumatoid arthritis, three showed definite reactive follicular hyperplasia with
      a prominence of plasma cells in the interfollicular areas, two showed subtotal
      replacement of the node by numerous sarcoid like granulomata, and one contained a
      large central area of necrosis with a surrounding palisade of histiocytes. In all
      six cases, focal areas of PAS positive eosinophilic hyaline material were
      present, which did not stain with Congo red. In some cases this hyaline material
      was focally calcified. In the seventh patient with rheumatoid arthritis the
      excised lymph node was almost totally replaced by similar PAS positive hyaline
      material which showed extensive areas of calcification. The lymph node removed
      from the patient with systemic sclerosis similarly showed almost total
      replacement by PAS positive hyaline material. CONCLUSION: In all cases the nodes
      contained PAS positive extracellular hyaline material to a greater or lesser
      degree. The lymph nodes from two of the patients with rheumatoid arthritis
      contained numerous sarcoid like granulomata, further indicating a possible
      association between sarcoidosis and rheumatoid arthritis. Pathologists and
      clinicians should include rheumatoid arthritis and systemic sclerosis in their
      differential diagnosis of lymph node hyalinisation of unknown aetiology.

PMID- 7510728
TI  - A comparison of 10% pentastarch and 5% albumin in patients undergoing open-heart
      surgery.
AB  - Colloids are useful in cardiac surgery to increase preload and improve cardiac
      output without the risks associated with blood transfusions. Pentastarch is a new
      low-molecular weight hydroxyethyl starch compound under investigation for this
      purpose. The authors compared, in a randomized fashion, 12 patients who received
      pentastarch and 17 patients who received albumin for volume expansion after open
      heart surgery. During the 24-hour study period there was no significant
      difference between the two groups with respect to systemic blood pressure, mean
      arterial pressure, cardiac index, right atrial pressure, and pulmonary capillary
      wedge pressure, with the exception of a higher mean arterial pressure and
      systolic blood pressure at 4 hours in the albumin group and higher heart rate at
      12 hours in the pentastarch group. In addition, postoperative prothrombin time,
      partial thromboplastin time, fibrinogen, platelets, and factor VIII levels were
      not significantly different between the two groups. There were no complications
      attributed to colloid administration. The hemodynamic parameters were further
      evaluated in a subset of 6 pentastarch and 9 albumin patients who received the
      first 500 mL of colloid in a similar time frame and under similar clinical
      conditions. The patients who received pentastarch showed a significantly greater
      increase in cardiac index than did the patients who received albumin. No
      significant change in other parameters were noted between the two groups. The
      authors conclude that pentastarch is as safe as albumin and may be a more
      effective volume expander than albumin when used in open-heart surgery patients.

PMID- 7510730
TI  - Motoneuron morphology in the dorsolateral nucleus of the rat spinal cord: normal
      development and androgenic regulation.
AB  - The rat lumbar spinal cord contains two sexually dimorphic motor nuclei, the
      spinal nucleus of the bulbocavernosus (SNB), and the dorsolateral nucleus (DLN).
      These motor nuclei innervate anatomically distinct perineal muscles that are
      involved in functionally distinct copulatory reflexes. The motoneurons in the SNB
      and DLN have different dendritic morphologies. The dendrites of motoneurons in
      the medially positioned SNB have a radial, overlapping arrangement, whereas the
      dendrites of the laterally positioned DLN have a bipolar and strictly unilateral
      organization. During development, SNB motoneuron dendrites grow exuberantly and
      then retract to their mature lengths. In this experiment we determined whether
      the adult difference in SNB and DLN motoneuron morphology was reflected in
      different patterns of dendritic growth during normal development. Furthermore,
      the development of both these nuclei is under androgenic control. In the absence
      of androgens, SNB dendrites fail to grow; testosterone replacement supports
      normal dendritic growth. Thus, we also examined the development of DLN dendrites
      for similar evidence of androgenic regulation. By using cholera toxin-horseradish
      peroxidase (BHRP) to label motoneurons retrogradely, we measured the morphology
      of DLN motoneurons in normal males, and in castrates treated with testosterone or
      oil/blank implants at postnatal day (P) 7, P28, P49, and P70. Our results
      demonstrate that in contrast to the biphasic pattern of dendritic development in
      the SNB, dendritic growth in the DLN was monotonic; the dendritic length of
      motoneurons increased more than 500% between P7 and P70. However, as in the SNB,
      development of DLN motoneuron morphology is androgen-dependent. In castrates
      treated with oil/blank implants, DLN somal and dendritic growth were greatly
      attenuated compared to those of normal or testosterone-treated males. Thus, while
      androgens are clearly necessary for the growth of motoneurons in both the SNB and
      DLN, their different developmental patterns suggest that other factors must be
      involved in regulating this growth.

PMID- 7510732
TI  - Corticofugal connections between the cerebral cortex and brainstem vestibular
      nuclei in the macaque monkey.
AB  - The distribution of cortical efferent connections to brainstem vestibular nuclei
      was quantitatively analysed by means of retrograde tracer substances injected
      into different electrophysiologically identified parts of the brainstem
      vestibular nuclear complex of five Java monkeys (Macaca fascicularis). Three
      polysensory vestibular areas were found to have a substantial projection to the
      vestibular nuclei: area 2v located at the tip of the intraparietal sulcus, the
      parietoinsular vestibular cortex (PIVC) covering the most occipital part of the
      granular insula (Ig) and the retroinsular area (Ri or reipt), and the
      dorsolateral part of the somatosensory area 3a ("area 3aV" neck/trunk region).
      From physiological recording experiments, these three cortical fields were known
      to contain many neurons responding to stimulation of semicircular canals as well
      as to optokinetic (area 2v, PIVC) and somatosensory stimuli (PIVC, area 3a).
      These three regions form the inner cortical vestibular circuit. Besides these
      polysensory vestibular cortical fields, three other circumscribed cortical
      regions of the macaque brain were also found to project directly to the brainstem
      vestibular nuclei: a circumscribed part of the postarcuate premotor cortex (area
      6pa), part of the agranular and the adjacent dysgranular cortex located around
      the cingulate sulcus (area 6c/23c), and a predominantly visual (optokinetic)
      association field located at the fundus of the lateral sulcus (area T3). These
      areas are known to have connections with the structures of the inner cortical
      vestibular circuit. Only a few efferent connections to the brainstem vestibular
      nuclei were found for the different parts of cytoarchitectonic area 7.
      Significant differences were found between the efferent innervation patterns of
      the axons originating in the six cortical areas mentioned and ending in the
      various compartments of the vestibular nuclear complex. Vestibular nuclei with a
      dominant output to the gaze motor system of the brainstem receive efferent
      connections preferably from the parietoinsular vestibular cortex. Vestibular
      structures with their primary output to skeletomotor centers, however, receive
      stronger efferent connections from areas 6pa and 3a. The ventrolateral nucleus,
      which sends efferent axons to both the oculomotor and skeletomotor systems of the
      brainstem and the spinal cord, also receives its main cortical efferents from the
      somatomotor area 6 and from area 3aV. Through these connections the cortical
      somatomotor system may directly influence vestibuloocular and vestibulocollic
      reflexes. It is speculated that the corticofugal connections to the vestibular
      brainstem nuclei are predominantly inhibitory, suppressing vestibular reflexes
      during cortically controlled goal-directed movements.

PMID- 7510729
TI  - Efferent projections of the sexually dimorphic area of the gerbil hypothalamus:
      anterograde identification and retrograde verification in males and females.
AB  - Outputs of the sexually dimorphic area (SDA) of the gerbil hypothalamus were
      identified by injecting Phaseolus vulgaris-leucoagglutinin into the medial or
      lateral SDA (mSDA, lSDA) in males and females. They were verified by injecting
      Fluoro-Gold or rhodamine-labeled beads into over half the areas that contained
      labeled fibers. Both anterograde and retrograde tracing showed that the mSDA and
      lSDA project to many of the same sites but often to differing degrees. The mSDA
      projects more heavily than the lSDA to many of their forebrain targets including
      the ventral part of the lateral septal nucleus, the bed nucleus of the stria
      terminalis, the medial tuberal area, and the anteroventral periventricular,
      arcuate, ventromedial and ventral premammillary nuclei of the hypothalamus. The
      lSDA projects more heavily than the mSDA to many of their mid- and hindbrain
      targets including the caudal, ventrolateral part of the periaqueductal gray, the
      retrorubral field, the pedunculopontine tegmental nucleus, and the locus
      coeruleus. In many other areas of the brain, the projections of the mSDA and lSDA
      are similar in size. These areas include the substantia innominata, the vascular
      organ of the lamina terminalis, the anterior amygdala, the posterior
      hypothalamus, the reuniens and paraventricular nuclei of the thalamus, and the
      pontine periaqueductal gray lateral to the fourth ventricle. The SDA pars
      compacta (SDApc), a small cell group embedded in the mSDA of males, projects to
      many fewer areas than the surrounding mSDA. It was strongly labeled when
      retrograde tracers were injected into the encapsulated part of the bed nucleus of
      the stria terminalis, the anteroventral periventricular nucleus, or the mSDA. It
      was also labeled from the vascular organ of the lamina terminalis, the caudal
      part of the lateral bed nucleus of the stria terminalis, the lSDA, the area
      lateral to the mSDA, the arcuate nucleus, the ventral premammillary nucleus, and
      the ventrolateral part of the ventromedial nucleus of the hypothalamus. Nothing
      resembling an SDApc was identified during retrograde tracing in females.

PMID- 7510734
TI  - Prevalence of antibodies to hepatitis C virus in a Dutch group of haemodialysis
      patients related to risk factors.
AB  - In January 1992, 122 chronic haemodialysis patients (> 9 months dialysis) from
      the University Hospital Utrecht and its outpatient dialysis facility were tested
      for the presence of anti-hepatitis C virus (HCV) antibodies. The objective was to
      identify risk factors for HCV infection in chronic haemodialysis patients in an
      attempt to explain the high prevalence of anti-HCV antibodies found among such
      haemodialysis patients. A second generation enzyme linked immuno-sorbent assay
      (EIA) was used as a screening test. Results were confirmed by a recombinant
      immunoblot assay and by the polymerase chain reaction (PCR). Four (3.3%) of 122
      patients reacted positively in the EIA screening test as well as in the
      immunoblot assay; three of these were positive using PCR. None of the patients
      with anti-HCV antibodies had received blood products other than blood from
      transfusions, none had markers for a hepatitis B virus (HBV) infection or
      admitted intravenous drug abuse. A total number of 2395 units of blood,
      unscreened for HCV, had been administered to our dialysis group, an average of
      19.6 (SD 44.7) units per patient. The seroprevalence of anti-HCV antibodies among
      blood donors in Utrecht was 0.03%. Patients with antibodies to HCV had been on
      dialysis longer than those dialysis patients without HCV antibodies (odds ratio
      1.8, 95% CI 0.99-3.29). We conclude that the risk for HCV infection for this
      dialysis group can only partially be attributed to unscreened blood transfusions.
      Haemodialysis itself may play a role in transmission of HCV.

PMID- 7510733
TI  - Health belief systems in perspective.
AB  - The author adopts a critical stance toward the assumptions, beliefs and
      behaviours underlying western biomedical tradition as it is enacted within the
      health care arena, in this paper. On the basis of a cross-cultural comparison of
      how health belief systems depict the nature of health, the nature of illness and
      the role of healers, this paper will analyse the degree to which traditions other
      than western biomedicine seem to influence much of our decision making and
      behaviour as practitioners and recipients of health care. Thus, locating our
      relationship to biomedical thought within the context of non-dominant belief
      systems provides an unusual angle from which to evaluate critically the way we
      think and behave. In concluding that western health beliefs are powerfully
      influenced by traditions far beyond biomedical ideology, the author raises
      implications for nursing's future directions as active participants in a global
      health movement.

PMID- 7510731
TI  - Substance P-, calcitonin gene-related peptide, growth-associated protein-43, and
      neurotrophin receptor-like immunoreactivity associated with unmyelinated axons in
      feline ventral roots and pia mater.
AB  - The spinal pia mater receives a rich innervation of small sensory axons via the
      ventral roots. Other sensory axons enter the ventral roots but end blindly or
      turn abruptly in hairpin loop-like formations and continue in a distal direction.
      In the present study, the content of substance P (SP)-, calcitonin gene-related
      peptide (CGRP)-, growth-associated protein (GAP-43)-, and low-affinity
      neurotrophin receptor protein (p75NGFr)-like immunoreactivity (-LI) associated
      with these different types of sensory axons was assessed with light and electron
      microscopic immunohistochemical techniques. In addition, the binding of
      antibodies against synthetic peptides representing unique sequences of residues
      in the products of the trk and trkB protooncogenes was analyzed. These genes
      encode membrane spanning proteins, which have been shown to constitute specific
      high affinity binding sites for several members of the nerve growth factor family
      of neurotrophic factors. The results of the present study imply that the ventral
      root afferents comprise several different types of sensory axons, which all
      contain SP-, CGRP-, GAP-43-, and p75NGFr-like immunoreactivities. In addition, at
      least some of the presumed sensory fiber bundles in ventral roots and the pia
      mater were immunoreactive for the trkB gene product. Moreover, leptomeningeal
      cells and nonneuronal cells of the ventral roots were shown to bind antibodies to
      both the trk and trkB gene products. The ventral root afferents seem to share
      their immunohistochemical pattern with pain-transducing axons at some other
      locations, such as the tooth pulp. The contents of SP- and CGRP-LI in sensory
      axons that reach the central nervous system (CNS) through the ventral root
      indicate that ventral root afferents may be involved in sensory mechanisms, such
      as the ventral root pain reaction, as well as in the control of the pial blood
      vessels. The demonstration of GAP-43 and neurotrophin receptor-immunoreactivities
      associated with unmyelinated fibers in ventral roots and the pia mater is
      discussed in relation to previous reports on postnatal plasticity in these axonal
      populations.

PMID- 7510736
TI  - Inhibition of nitric oxide synthesis increases blood pressure in healthy humans.
AB  - OBJECTIVE: To examine whether endogenous production of the endothelium-derived
      vasodilator nitric oxide influences blood pressure in healthy humans. METHODS:
      After preliminary pilot dose-ranging studies, 3 mg/kg NG-monomethyl-L-arginine (L
      NMMA), an inhibitor of nitric oxide synthase, and saline placebo were infused
      intravenously over 5 min to eight healthy subjects in a two-phase, randomized,
      single-blind crossover study. Blood pressure and cardiac and renal function were
      measured. RESULTS: Compared with placebo, L-NMMA increased mean arterial pressure
      by 10%, decreased heart rate by 19%, decreased cardiac index by 25% and increased
      calculated total peripheral resistance by 46%. Effects were maximal 10-15 min
      after starting L-NMMA infusion. Urinary sodium and fractional sodium excretions
      were increased by L-NMMA, but creatinine clearance was unchanged. CONCLUSIONS:
      Basal generation of nitric oxide influences total peripheral resistance and blood
      pressure in healthy humans. The natriuresis induced by L-NMMA may be related to
      the increase in blood pressure, or arise from inhibition of the intrarenal
      actions of nitric oxide. Any decrease in nitric oxide generation, as has been
      postulated to occur in essential hypertension, could have substantial effects on
      blood pressure and tissue blood flow.

PMID- 7510735
TI  - Calcium channels in vitamin B6 deficiency-induced hypertension.
AB  - OBJECTIVE: To compare the acute hypotensive effects of various calcium channel
      modulators in vitamin B6-deficient hypertensive (B6DHT) rats. METHODS: Adult male
      Sprague-Dawley rats were fed a vitamin B6-deficient diet for 7-10 weeks, during
      which systolic blood pressure (SBP) was measured in the B6DHT and control rats,
      using tail-cuff plethysmography. The effects of the calcium antagonists
      nifedipine, verapamil, diltiazem and (-)-202-791 on SBP were determined in
      conscious B6DHT rats. The effect of the calcium agonist BAY K 8644 on the SBP of
      rats fed various levels of pyridoxine was also determined. RESULTS: All of the
      calcium antagonists used were effective in lowering the SBP of the B6DHT rats
      with the rank order of potency: nifedipine > (-)-202-791 > (+/-)-verapamil >
      diltiazem. BAY K 8644 elevated the SBP of older rats fed a normal commercially
      available diet, but had no effect when the vitamin B6 content of their diet was
      increased or removed for a short period. CONCLUSION: Calcium channel function
      appears to be related to vitamin B6 status in the rat.

PMID- 7510737
TI  - Effect of dietary salt restriction on urinary serotonin and 5-hydroxyindoleacetic
      acid excretion in man.
AB  - OBJECTIVE: To determine the effect of dietary salt restriction on urinary
      excretion of serotonin and its principal metabolite 5-hydroxyindoleacetic acid (5
      HIAA) in man. DESIGN: We studied 16 healthy male volunteers (age range 20-28
      years) who ate a standard diet containing 20 mmol/day NaCl, to which either 220
      mmol/day NaCl or placebo was added as a supplement for 1 week each, according to
      a randomized, single-blind crossover design. METHODS: Urinary excretion of
      serotonin, 5-HIAA, noradrenaline and vanillylmandelic acid (VMA) were measured
      during the low- and high-salt periods using reverse-phase high-performance liquid
      chromatography. RESULTS: During the low-salt diet, 24-h urinary excretion of
      serotonin increased by 42%, accompanied by a 52% rise in the excretion of 5-HIAA.
      Salt restriction also increased noradrenaline excretion by 77% and VMA excretion
      by 40%. Regression analysis revealed a strong positive relationship between the
      excretion of serotonin and of noradrenaline (r = 0.84, P < 0.001) and between
      that of 5-HIAA and of VMA (r = 0.74, P < 0.001). CONCLUSIONS: Salt restriction
      stimulates the serotonergic system in man. Stimulation of this system, in
      conjunction with the sympathetic nervous system, may contribute to renal sodium
      conservation during dietary salt restriction in man.

PMID- 7510739
TI  - Mechanisms of T cell contact-dependent B cell activation.
AB  - It has been reported that activated Th cells express CD40 ligand, and the
      interaction of the CD40 ligand and CD40 on B cells results in B cell cycle entry.
      In this report, mechanisms of B cell activation induced by CD40-CD40 ligand
      interaction were studied by using an activated Th cell membrane as a source of
      CD40 ligand. The rise in cAMP concentration and tyrosine phosphorylation of a 69
      kDa protein were induced in B cells stimulated with the activated Th cell
      membrane, and both of them were suppressed by the inclusion of soluble CD40 in
      cultures. The membrane stimulation did not elicit either inositol phosphates
      metabolism nor elevation of intracellular Ca2+ concentration. Protein kinase C
      depletion did not affect the proliferation, rise in cAMP level, or the 69-kDa
      protein tyrosine phosphorylation. Addition of anti-CD45 to the culture resulted
      in suppression of the B cell proliferation as well as the 69-kDa protein tyrosine
      phosphorylation. Furthermore, a protein kinase A inhibitor, H-89, suppressed the
      B cell proliferation induced by the membrane. These results indicate that both
      protein tyrosine kinase and protein kinase A were involved in the signal
      transduction pathway for the B cell proliferation evoked by the CD40-CD40 ligand
      interaction in Th cell contact-dependent B cell proliferation.

PMID- 7510738
TI  - Monoclonal antibody 2D10 recognizes a novel T cell costimulatory molecule on
      activated murine B lymphocytes.
AB  - We have developed a panel of rat mAbs against dibutyryl cAMP-activated 5C2 cells.
      In this panel, one mAb, 1G10, recognized murine B7. Another mAb designated 2D10
      did not bind to murine B7 but could recognize a surface molecule expressed only
      on dibutyryl cAMP-activated 5C2 mouse B lymphoma cells or on LPS-stimulated
      splenic B cells. This new molecule is referred to as early T cell costimulatory
      molecule-1 (ETC-1). From both activated 5C2 cells and splenic B cells, mAb 2D10
      immunoprecipitated a 59- to 60-kDa protein, which was different from the 47- to
      55-kDa murine B7 protein precipitated from the same cell populations. FACS
      analysis showed that, in contrast to B7, the expression of ETC-1 on 5C2 cells was
      induced by lower concentrations of dibutyryl cAMP and displayed a faster
      kinetics. LPS-stimulated splenic B cells expressed relatively low levels of B7
      and much higher levels of ETC-1. Importantly, in an Ag presentation assay using
      activated 5C2 cells as APC, the secretion of IL-2 by C8A3 T hybrids was partially
      inhibited by mAb 2D10 alone and completely blocked by combination use of mAbs
      2D10 and 1G10 in a dose-dependent and synergistic fashion. In a one-way primary
      MLR, mAb 2D10 alone at 0.1 to 1 microgram/ml inhibited T cell proliferation by 19
      to 56%. However, an additive blocking effect (up to 76%) was observed when two
      mAbs were added in combination. Thus, our data have demonstrated that a novel T
      cell costimulatory molecule is present on activated murine B cells, which, in
      cooperation with B7, may play a critical role in optimal T cell activation.

PMID- 7510740
TI  - CD40 ligand acts as a costimulatory signal for neonatal thymic gamma delta T
      cells.
AB  - The stimulatory requirements for T cells bearing gamma delta T cell receptors are
      distinct from those of alpha beta T cells. We have analyzed the ability of the
      CD40 ligand (CD40L) to activate neonatal thymic gamma delta T cells. CD40L is
      expressed on activated T cells and has been shown to induce B cell proliferation
      and Ig secretion as well as monocyte activation. We now demonstrate that, in the
      presence of an anti-TCR-gamma delta Ab, CD40L is able to induce the proliferation
      of neonatal thymic gamma delta cells. The presence of CD40L also leads to
      enhanced expression of a variety of activation-associated Ag including CD25,
      CD69, CD44, and Ly6C. In addition to proliferation, CD40L induces lectin-mediated
      cytolytic activity in thymic gamma delta T cells as well as the production of IFN
      gamma and TNF-alpha. We were unable to detect IL-2 or IL-4 production in response
      to CD40L, and Ab-blocking studies indicate that the mechanism of activation
      appears to involve IL-1 but is independent of IL-2, IL-4, and IL-7. These results
      suggest that, in addition to its effects on B cells and monocytes, CD40L can
      costimulate the activation of thymic gamma delta T cells.

PMID- 7510742
TI  - Unusual topology of an HLA-B27 allospecific T cell epitope lacking peptide
      specificity.
AB  - Recognition of MHC + peptide complexes by TCRs is thought to involve a large
      surface formed by exposed residues from the bound peptide and from the alpha
      helices of the MHC protein. This interaction appears to be essentially
      symmetrical in the positioning of the TCR relative to the MHC molecule. In this
      study the topology of HLA-B27 recognition by an alloreactive TCR, 64.8P, has been
      analyzed with a panel of site-specific mutants that have changes at multiple
      positions along the peptide binding site of HLA-B27. Abrogation of transfectant
      target cell lysis by CTL 64.8P was obtained only with some mutations in the
      peptide side chain binding pockets A and B, whereas little or no effect was
      observed with mutations outside these pockets. CTL 64.8P efficiently lysed murine
      transfectant cells, including HLA-B27+ RMA-S cells. Recognition of this latter
      transfectant was more efficient upon increased HLA-B27 expression at 26 degrees
      C. The uneven distribution of mutations affecting HLA-B27 allorecognition by CTL
      64.8P strongly suggests an asymmetrical topology in the interaction of this TCR
      with HLA-B27, in which most of the binding energy is provided by contacts with
      HLA-B27 and/or peptide residues located close to pockets A and B, with little
      contribution from other areas of the MHC or peptide molecules. Its conservation
      in RMA-S cells further suggests that the epitope recognized by CTL 64.8P is
      either peptide-independent or requires any of a set of peptides having the same
      amino-terminal residues.

PMID- 7510743
TI  - Sensitivity of human leukemia cells in exponential or stationary growth phase to
      anti-CD5 immunotoxins. Role of intracellular processing events.
AB  - We have assayed the sensitivity of Jurkat cells in different growth phases to an
      anti-CD5-ricin A chain (ST.1-RTA) immunotoxins (IT). Jurkat cells proliferated
      exponentially until a stationary growth phase was reached. Proliferating and
      stationary cells displayed marked differences in sensitivity to ST.1-RTA
      treatment; the time required to kill one log of target cells (T10) was 70 h in
      proliferating and 12 h in stationary cells, respectively. Differences in
      sensitivity to IT treatment were greatly diminished by the addition of the IT
      enhancer monensin (T10 = 4.9 and 3.5 h in proliferating and stationary cells,
      respectively). Binding and internalization studies carried out with
      fluoresceinated ST.1 mAb revealed that the higher sensitivity of stationary cells
      to ST.1-RTA treatment was not due to an increased uptake or to faster
      internalization kinetics of IT molecules in this cell population; rather, our
      data indicated that a different intracellular routing of IT molecules took place
      in the two cell populations. Mathematical modeling of experimental data allowed
      us to calculate the efficiency of the intracellular transport of IT molecules
      toward a subcellular compartment facilitating toxin translocation to the cell
      cytosol. The IT intracellular processing in stationary cells was 5.5-fold more
      efficient than in proliferating cells. This value strictly correlated with the
      higher sensitivity of the stationary cell population to ST.1-RTA treatment.

PMID- 7510741
TI  - Molecular cloning of a lamprey homologue of the mammalian MHC class III gene,
      complement factor B.
AB  - To elucidate the origin and evolution of the complement system and the MHC, we
      isolated cDNA clones for the MHC class III complement factor B (Bf) gene from
      lamprey, one of the most primitive extant vertebrates. A part of the serine
      protease domain of the lamprey Bf was amplified by reverse transcriptase-PCR
      using the degenerated primers corresponding to the conserved amino acid stretches
      between the mouse Bf and C2 sequences. A full-length lamprey Bf cDNA clone was
      isolated from the lamprey liver cDNA library using a PCR-amplified DNA clone as a
      probe. The deduced amino acid sequence of 763 residues showed essentially the
      same domain structure as mammalian Bf or C2, consisting of three short consensus
      repeat domains, a von Willebrand domain, and a serine protease domain. Lamprey Bf
      showed 33 and 29% overall amino acid similarity to mouse Bf and mouse C2,
      respectively, whereas amino acid similarity between mouse Bf and mouse C2 was
      36%, suggesting that the gene duplication of Bf/C2 occurred in the main line of
      vertebrate evolution after the divergence of cyclostomes. This is the first
      report of the molecular cloning from cyclostomes of a component of the mammalian
      MHC that offers the possibility of genetic analysis of the presumably primitive
      MHC of cyclostomes.

PMID- 7510744
TI  - Cross-linking of ICAM-1 induces co-signaling of an oxidative burst from
      mononuclear leukocytes.
AB  - Cell adhesion molecules were first described as accessory molecules simply to
      bridge one cell to another. More recently, it has been realized that these
      molecules also transmit signals from outside of the cell to inside. We show that
      cross-linking of the ICAM-1 on the cell membrane with anti-ICAM-1 mAb and F(ab')2
      fragments of goat anti-MIgG in the presence of suboptimal levels of the bacterial
      peptide FMLP results in co-stimulation of an oxidative burst from CD14 expressing
      PBMCs. The amplitude of the oxidative response was less than the oxidative burst
      induced by CD18 cross-linking, whereas the response was more prolonged. On the
      other hand, cross-linking by anti-L-selectin mAb plus F(ab')2 fragments of goat
      anti-MIgG induced a minimal oxidative burst that was not significantly greater
      than the response generated by anti-L-selectin mAb alone. The addition of an
      excess of soluble ICAM-1 to compete for the anti-ICAM-1 mAb inhibits the
      oxidative burst in response to ICAM-1 cross-linking but not to CD18 cross
      linking. These results suggest that ICAM-1 is capable of delivering a
      transmembrane signal into CD14-positive PBMC.

PMID- 7510746
TI  - Immunity to TCR peptides in multiple sclerosis. I. Successful immunization of
      patients with synthetic V beta 5.2 and V beta 6.1 CDR2 peptides.
AB  - Immunization with disease-associated TCR V region peptides is an effective
      treatment for experimental autoimmune encephalomyelitis. Myelin basic protein
      specific T cells, which induce experimental autoimmune encephalomyelitis in many
      animal strains, may be important in the pathogenesis of multiple sclerosis.
      Myelin basic protein-specific T cell clones from some multiple sclerosis patients
      preferentially use TCR V genes from the V beta 5.2 and V beta 6.1 families. To
      assess the safety and immunogenicity of TCR V beta 5.2 and V beta 6.1 peptides,
      we injected 11 multiple sclerosis patients with varying doses of two synthetic
      peptides, TCR V beta 5.2(39-59) and V beta 6.1(39-59), encompassing the CDR2
      region of these V gene families. Low doses (100 to 300 micrograms) of peptide
      induced T cell immunity in 7 of 11 patients to one or both peptides. Delayed type
      hypersensitivity skin responses to the peptides were observed in three of seven
      responders, and TCR peptide-specific Ab occurred in two of seven T cell
      responders. Low doses of TCR peptides produced no side effects and did not cause
      broad spectrum immunosuppression. Synthetic TCR V region peptides can induce T
      cell immunity safely in humans and may prove useful in treating human autoimmune
      diseases.

PMID- 7510745
TI  - Characterization of rabbit complement component C8. Functional evidence for the
      species-selective recognition of C8 alpha by homologous restriction factor
      (CD59).
AB  - Protection of host cells from lysis by the C5b-9 cytolytic complex is provided by
      a membrane-associated protein (CD59) that interacts with homologous C8 and C9
      during C5b-9 assembly. This interaction restricts normal formation and function
      of the complex, thereby protecting cells from attack by homologous C. In this
      study, rabbit C8 was purified and characterized and used to investigate the role
      of the individual C8 subunits in homologous restriction and the basis for species
      selectivity by human CD59. Exchanging the disulfide-linked C8 alpha-gamma dimer
      in human C8 with one from rabbit was found to be sufficient to overcome
      restriction by human Es. Activity of the hybrid C8 and rabbit C8 toward these
      target cells was equivalent, thus establishing that restriction is not dependent
      on the species of C8 beta. Because C8 gamma was previously shown to have no role
      in restriction, these results suggest that within C8, structural determinant(s)
      recognized by CD59 reside solely on C8 alpha. Sequences determined from full
      length cDNA clones for rabbit C8 alpha, C8 beta, and C8 gamma support this
      conclusion. All three subunits are strikingly similar to human with regard to
      length, m.w., N- and C-terminal residues, conserved cysteines, and overall
      sequence. However, when sequences are compared under high stringency, a single
      segment of extended sequence dissimilarity is detected between the two species of
      C8 alpha. Within human C8 alpha, this 37-residue segment resides near the
      putative membrane-interacting region and may constitute a human CD59 recognition
      site.

PMID- 7510748
TI  - Effect of antibody valency on interaction with cell-surface expressed HIV-1 and
      viral neutralization.
AB  - F(ab) and F(ab')2 fragments of the human mAb, F105, were compared to intact IgG1
      for binding to the CD4 binding site of HIV-1/gp120 on the surface of infected
      cells and viral neutralization. F105 IgG1 and F(ab')2 bound to IIIB, MN, and RF
      infected cells and neutralized these strains in an identical fashion, whereas
      strain-specific differences were observed in F(ab) activity. Although F105 F(ab)
      bound with equivalent affinity to IIIB-infected cells, there was a 4- to 10-fold
      decrease in the neutralization of IIIB by monovalent F(ab) compared to the
      bivalent molecules. F105 F(ab) demonstrated both diminished binding and
      neutralization of the MN strain and failed to bind or neutralize the RF strain.
      When cooperativity of V3 loop antibody (V3ab) with F105 IgG and fragments was
      examined, the binding of F105 IgG and F(ab')2 to IIIB-, MN-, or RF-infected cells
      was modestly enhanced by V3ab; viral neutralization was substantially enhanced by
      the combination of V3ab and F105 IgG and F(ab')2. The combination of F105 F(ab)
      with V3ab also resulted in significant cooperative neutralization of IIIB and MN,
      but the lack of F105 F(ab) binding and neutralization of RF was unaltered by
      V3ab. These results suggest that bivalent interaction may be important in binding
      and neutralization of virus, and support the notion that this interaction may
      depend on conformational changes in oligomeric gp120 on intact virions and cell
      surface rather than on affinity or steric effects.

PMID- 7510747
TI  - Immunity to TCR peptides in multiple sclerosis. II. T cell recognition of V beta
      5.2 and V beta 6.1 CDR2 peptides.
AB  - The biased expression of V beta 5.2 and V beta 6.1 by T cells specific for myelin
      basic protein (BP) has led to our use of TCR peptides from these V gene sequences
      to induce anti-TCR immunity in patients with multiple sclerosis (MS). Injection
      of V beta 5.2-39-59 or V beta 6.1-39-59 peptides significantly increased the
      peptide specific T cell frequency in 7 of 11 MS patients, often with an
      accompanying delayed hypersensitivity reaction at the injection site. Here, we
      validate these cellular immune responses by characterizing TCR peptide specific T
      cells from an MS patient with biased V beta 5.2 expression in BP reactive T cells
      before treatment with TCR peptides, and from two MS patients in whom the
      frequencies of anti-TCR peptide specific T cells were significantly boosted after
      injection with low doses of TCR peptides. In both cases, T cell lines were
      established with relative ease, especially after boosting with the peptides. A V
      beta 5.2-39-59 reactive line responded selectively to the boosting peptide and
      was restricted by both MHC class I (HLA-B7) and MHC class II (HLA-DR2) molecules.
      Characterization of 22 clonal isolates revealed that the responding T cells were
      predominantly activated CD4+CD8lo, circulating memory cells restricted by either
      HLA-B7 or HLA-DR2, that utilized mainly V beta 4, V beta 6, V beta 12, and V beta
      14, but not V beta 5.2 in their TCR. T cell isolates specific for V beta 6.1-39
      59 possessed similar characteristics but contained specificities cross-reactive
      with an N-terminal sequence on V beta 5.2-39-59. Upon stimulation with peptide or
      Con A, the TCR peptide specific T cell lines had increased message production for
      IFN-gamma, GM-CSF, IL-4, IL-5, and to a lesser degree, IL-2. This lymphokine mRNA
      profile differed from a BP-specific T cell line that produced message for IFN
      gamma and GM-CSF but low or absent levels of IL-4 and IL-5. The extensive
      parallels between human T cells specific for V beta 5.2 and V beta 6.1 CDR2
      peptides and rat T cells specific for V beta 8.2 CDR2 peptide that are highly
      protective against experimental encephalomyelitis strengthen the rationale for
      the therapeutic use of TCR peptides in human autoimmunity.

PMID- 7510750
TI  - High resolution epitope mapping of an anti-DNA autoantibody using model DNA
      ligands.
AB  - Although Ab-DNA complexes are involved in the pathogenesis of SLE, the mechanism
      by which anti-DNA recognize their DNA targets remains elusive. We have designed
      and synthesized small test DNA ligands that model ssDNA and dsDNA determinants
      commonly recognized by anti-DNA autoantibodies. These ligands were used in DNA
      footprinting assays to conduct a high resolution epitope-mapping study of anti
      ssDNA BV04-01, which is typical of anti-ssDNA expressed in (NZB x NZW)F1 mice. We
      find that BV04-01 recognizes the ssDNA, but not dsDNA, epitopes presented on the
      test ligands, and makes specific base and backbone contacts with the DNA.
      Moreover, BV04-01 binding induces conformational changes in both the single
      stranded and duplex region of the ligands. The epitope-mapping data is used in
      conjunction with computational molecular modeling to construct a three
      dimensional model of a BV04-01-ligand complex. The salient aspects of this model
      are consistent with many features observed in the crystal structure of BV04-01
      liganded to d(pT)3. This work extends previous anti-DNA binding studies and
      attempts to provide a unified approach that draws upon the merits of many
      precedented experimental methods to assemble three-dimensional structures of anti
      DNA-DNA complexes. Analysis of these structures may ultimately help guide the
      development of molecules designed to inhibit anti-DNA binding in SLE.

PMID- 7510749
TI  - Purification and characterization of Yersinia enterocolitica envelope proteins
      which induce antibodies that react with human thyrotropin receptor.
AB  - Graves' disease is an autoimmune disease mediated by autoantibodies to the
      thyrotropin receptor (TSHR). Several studies have suggested that the development
      of Graves' disease may be linked to infection with the enteric pathogen Yersinia
      enterocolitica. Using the purified recombinant extracellular domain of human TSHR
      (ETSHR), we have recently shown that immunization of mice with Y. enterocolitica
      results in the production of antibodies capable of reacting with the ETSHR. In
      this study, we identify two low molecular weight (5.5 kDa and 8 kDa) envelope
      proteins of Yersinia containing epitopes that are crossreactive with the TSHR.
      Identification of these crossreactive envelope proteins was achieved by Western
      blotting using affinity-purified anti-Y. enterocolitica antibodies that
      specifically react with the TSHR and, conversely, for envelope proteins of
      Yersinia. Confirmation that these Yersinia proteins contained crossreactive
      epitopes with the ETSHR was obtained by immunizing mice with partially purified
      envelope proteins, which resulted in the production of Abs that recognized the
      ETSHR. Further, some of the cross-reactive envelope proteins were purified with
      SDS-PAGE and HPLC. The crossreactive envelope proteins were shown to be
      chromosomally encoded, exposed on the surface of bacteria, and produced by
      virulent as well as avirulent strains of Yersinia (Y. pestis, Y.
      pseudotuberculosis, Y. enterocolitica VW+, and Y. enterocolitica VW-). These
      results identify for the first time the Yersinia envelope proteins that are
      crossreactive with the ETSHR. Availability of these proteins will allow future
      studies to determine whether patients with Graves' disease have a unique immune
      response against these proteins when compared with healthy individuals.

PMID- 7510753
TI  - Analysis of the population of human T cell receptor gamma and delta chain
      variable region subfamilies by reverse dot blot hybridization.
AB  - We have developed a simple method to analyze the population of T cell receptor
      (TCR) gamma and delta chain variable (V) region subfamilies by the application of
      reverse dot blot hybridization, which was originally developed for the analysis
      of human HLA-DR polymorphism. The four oligonucleotides corresponding to each TCR
      gamma V region subfamily and the six oligonucleotides to each TCR-delta V region
      gene were synthesized, and tailed with dTTP. The cDNA was amplified by ligation
      mediated PCR in the presence of biotinylated deoxynucleotides. Hybridization
      between immobilized specific oligoprobes and biotinylated target DNA was
      nonradioactively detected by a reaction using alkaline phosphatase. The
      population of the V region subfamilies of TCR-gamma and -delta in PBL analyzed by
      reverse dot blot hybridization described here showed good correlations with the
      result of colony hybridization.

PMID- 7510752
TI  - Competitive RT-PCR ELISA: a rapid, sensitive and non-radioactive method to
      quantitate cytokine mRNA.
AB  - We have developed a non-radioactive method to quantitate precisely levels of gene
      expression. This method is based on RT-PCR (reverse transcriptase-polymerase
      chain reaction) with an RNA competitor, followed by the covalent capture of the
      amplified DNA onto the wells of microtiter plates, and the quantitation of the
      PCR product by oligonucleotide hybridization and ELISA (enzyme-linked
      immunosorbent assay). The assay can reproducibly detect 1 zeptomole mRNA. The
      assay was successfully used to quantitate mRNA levels of the T cell derived
      cytokines interleukin-2, interleukin-4 and interferon-gamma in resting and
      stimulated human lymphocytes. Because it is performed in a microtiter ELISA
      format, this rapid, sensitive and non-radioactive method should facilitate
      measurements of gene expression, particularly in large clinical studies.

PMID- 7510751
TI  - Rheumatoid synovium is enriched in mature antigen-presenting dendritic cells.
AB  - Monocytes and dendritic cells (DC) can be purified from fresh peripheral blood
      (PB) based on their expression of CD33, CD13, and CD14. Whereas DC can be
      identified as CD33+ CD14dim or CD13+CD14dim cells, monocytes can be identified as
      CD33+CD14bright or CD13+CD14bright cells. Rheumatoid synovial fluid (SF) and
      synovial tissue (ST) non-T cells were found to be enriched in CD33+CD14dim cells
      compared with PB. Whereas 4 to 14% of normal or rheumatoid PB non-T cells were
      CD33+ and CD14dim, in rheumatoid SF or ST these cells comprised 20 to 45% of non
      T mononuclear cells. Synovial CD33+CD14dim cells assumed a typical dendritic
      morphology on in vitro culture. Freshly isolated CD33+CD14dim PB DC precursors
      express low levels of HLA-DQ, CD40, and B7, which increase after in vitro
      incubation. In contrast, freshly isolated SF DC constitutively expressed these
      markers, and increased densities of HLA-DR and MHC class I molecules. Rheumatoid
      SF DC showed a specifically enhanced ability to stimulate autologous PB T cells
      compared with PB DC, or PB or SF monocytes. PB DC or monocytes preincubated in
      granulocyte-macrophage-CSF, TNF-alpha, or both cytokines exhibited enhanced
      expression of HLA-DR. Furthermore, DC preincubated in both granulocyte-macrophage
      CSF and TNF-alpha were better stimulators of the autologous MLR than DC
      preincubated in medium, or in either cytokine alone. The data indicate that DC
      are enriched in rheumatoid SF and ST, and display a more differentiated phenotype
      than PB DC. These results suggest that PB DC accumulate in the synovium where
      they undergo phenotypic and functional differentiation in situ, which may be
      mediated by local cytokines. DC may play an important role in the ongoing
      presentation of antigen to autoreactive T cells in RA synovium.

PMID- 7510754
TI  - Hapten-mediated identification of cell membrane antigens using an anti-FITC
      monoclonal antibody.
AB  - A monoclonal anti-FITC antibody (F4/1) was produced and demonstrated to be
      specific for both the free and protein-conjugated (either soluble or cell-bound)
      form of fluorescein, or carboxyfluorescein. When mouse thymocytes were labelled
      with a novel fluorescein derivative 5(6)-carboxyfluorescein succinimidyl ester
      (CFl-NSE), the incorporation of fluorescein was predominantly membrane-bound as
      demonstrated immunohistochemically. The coupling of CFl-NSE to cells displays a
      random distribution pattern as shown by immunoblotting of cell extracts prepared
      by detergent solubilization of CFl-NSE-labelled thymocytes. In addition, the Thy
      1.2 antigen immunoprecipitated from a CFl-NSE-labelled thymocyte lysate with a
      rat monoclonal antibody (Mab) could be detected using the anti-FITC Mab. The
      molecular weight of the immunoprecipitated material could be estimated
      immediately by reference to the FITC-labelled molecular weight markers
      electrophoresed simultaneously.

PMID- 7510755
TI  - A consensus primer to amplify both alpha and beta chains of the human T cell
      receptor.
AB  - The use of reverse transcriptase in conjunction with the polymerase chain
      reaction (RT-PCR) has proven invaluable in the analysis of the T cell receptor
      (TCR) repertoire of different populations of T cells. However, the presence of a
      variable region in the T cell receptor has hindered the design of primers for the
      5' end of the TCR cDNA. We describe the design and use of a degenerate consensus
      primer that allows amplification of both the alpha and beta chains of the human
      TCR. We have used this primer in the analysis of the TCR distribution of T cell
      clones, peripheral blood lymphocytes and lymphocytes residing in tissue. In
      addition, the primer has allowed the identification of an alternative splice site
      in the beta chain constant region which cannot translate into a functional
      constant region. We have found the primer to be easy to use, sensitive and
      specific.

PMID- 7510756
TI  - Detection of cell specific cluster determinant expression by reverse
      transcriptase polymerase chain reaction.
AB  - We describe a new, rapid, sensitive, and reproducible method for examining gene
      expression of several cell specific surface cluster determinants, CD2, CD3-gamma,
      CD4, CD8-beta, CD14, CD19, CD20, CD23, and CD25-alpha, and terminal
      deoxynucleotidyl transferase which heretofore have been commonly detected by flow
      cytometry. The method presented uses the reverse transcriptase polymerase chain
      reaction (RT-PCR) to analyze CD gene expression in stable human cell lines,
      peripheral blood lymphocytes, bone marrow, and lymph node cells. Polymerase chain
      reaction products were quantitated by incorporation of radiolabeled nucleotide
      during PCR and the amount of nucleotide incorporated into DNA was measured by ion
      exchange filter chromatography. The usefulness of this methodology is
      demonstrated in an analysis of peripheral blood samples from a patient who
      presented with B cell deficiency. Results of analyses of peripheral blood samples
      from this patient by flow cytometry and RT-PCR are similar except that the
      increased sensitivity of RT-PCR permitted the detection of CD19, CD20, and CD23
      in the blood samples of this patient who otherwise appeared to be lacking in all
      markers of B cell development.

PMID- 7510757
TI  - Assessment of the anti-c-kit monoclonal antibody YB5.B8 in affinity magnetic
      enrichment of human lung mast cells.
AB  - The monoclonal antibody, YB5.B8 binds to the second domain of the c-kit proto
      oncogene product on human mast cells, a receptor associated with tyrosine kinase
      activity. This molecule is involved with cell proliferation, maturation and
      viability as well as cell activation and its natural ligand is stem cell factor
      (SCF). We have used this antibody coupled to Dynabeads to perform positive
      affinity enrichment of human lung mast cells. This procedure results in
      enrichment of mast cells from 2.6 +/- 0.3% to 85.0 +/- 1.6% purity (n = 29) with
      yields of 41.9 +/- 3.7% (n = 29). As YB5.B8 interacts with the same receptor
      domain as does SCF, it is important to demonstrate that this procedure does not
      modify mast cell function. Incubation of mast cells with 1-5000 ng/ml YB5.B8 for
      30 min neither induced histamine release nor modulated histamine release induced
      by anti-IgE. Furthermore, incubation with YB5.B8 did not alter prolonged culture
      with SCF. Examination of cells enriched using YB5.B8 showed that they had a
      normal histamine content (3.8 +/- 0.3 pg/cell compared with 3.9 +/- 0.7 pg/cell
      unpurified, n = 20) and had unchanged behaviour in both histamine secretion and
      cell survival studies. These studies indicate that YB5.B8 does not influence mast
      cell function and thus its use in magnetic affinity purification procedures
      offers a simple and effective method for enriching human mast cell preparations.

PMID- 7510758
TI  - Radioimmunoassays for the C-terminus of prothymosin alpha and the N-terminus of
      parathymosin alpha for the measurement of the levels of alpha-thymosins in human
      cancer.
AB  - A radioimmunoassay specific for the C-terminus of human prothymosin alpha was
      developed using the synthetic peptide [Cys-Aca degrees]-human prothymosin alpha
      (90-109)-OH coupled to KLH as antigen and the analogue [Tyr-Aca degrees]-human
      prothymosin alpha (90-109)-OH labelled with 125I as tracer. The radioimmunoassay
      measured intact prothymosin alpha, in the range of 2-100 pmol and does not cross
      react with the partly homologous polypeptide parathymosin alpha. A major epitope
      was located in the segment 95-107. A radioimmunoassay specific for the N-terminus
      of human parathymosin alpha, also measuring intact parathymosin alpha in the
      range of 1-20 pmol and not cross-reacting with prothymosin alpha, was developed
      using the synthetic peptide [Cys-Aca degrees]-human parathymosin alpha (1-30)-OH
      as antigen coupled to KLH and the analogue [Tyr-Aca degrees]-human parathymosin
      alpha (1-10)-OH labelled with 125I as tracer. A major epitope was located in the
      segment 1-10. These radioimmunoassays, together with a previously established
      radioimmunoassay for the N-terminus of prothymosin alpha, permitted the
      identification of the molecular forms of the cross-reactive materials in both
      normal and neoplastic breast tissue extracts as intact prothymosin alpha and
      parathymosin alpha. It was also possible to reveal significantly higher levels of
      both alpha-thymosins in breast cancer tissue compared to the nearby healthy
      tissue--the mean of 14 samples was over 14-fold higher--suggesting a role of both
      prothymosin alpha and parathymosin alpha in cell proliferation. The reported
      radioimmunoassays are expected to facilitate the search for prognostic and/or
      diagnostic applications of these polypeptides in human cancer.

PMID- 7510760
TI  - Retinoblastoma protein monoclonal antibodies with novel characteristics.
AB  - We have developed a family of monoclonal antibodies directed against the
      retinoblastoma gene product (p110RB). One of these monoclonal antibodies, 3C8,
      binds p110RB near the C-terminal end of the protein (aa886-aa905). It was
      characterized by immunoblotting, ELISA, fluorescence-activated flow cytometry and
      immunohistostaining. It was shown to be useful for the detection of p110RB in
      formalin-fixed and paraffin-embedded tissue sections. Because 3C8 binds outside
      of regions shown to be involved in p110RB interactions with other cellular
      proteins, it may be an especially useful reagent for the reliable detection of
      p110RB in tumor cells, and for the isolation by affinity chromatography of p110RB
      complexes with other cellular proteins.

PMID- 7510759
TI  - Screening for autoantibodies to the nucleolar U3- and Th(7-2) ribonucleoproteins
      in patients' sera using antisense riboprobes.
AB  - In this study we report the detection of autoantibodies to the nucleolar U3- and
      Th(7-2) ribonucleoprotein (RNP) particles in sera from patients with connective
      tissue diseases. The method described employs radioactively labelled antisense U3
      and Th RNA which are hybridized to immunoprecipitated U3- or Th RNA from a HeLa
      cell extract. Of the 66 sera that were screened with this method seven sera (11%)
      precipitated only Th RNP, 16 sera (24%) precipitated only U3 RNP and 4 sera (6%)
      precipitated both U3- and Th RNP. Both anti-U3 RNP and anti-Th RNP activity
      appeared to be mostly associated with scleroderma or scleroderma-associated
      diseases. Using this method we also showed that some of the Th RNP particles in a
      cell extract are associated with the La autoantigen. We conclude that for the
      identification of immunoprecipitated RNAs this method is very sensitive and
      provides unambiguous data.

PMID- 7510761
TI  - Factors affecting the fine specificity and sensitivity of serum antiganglioside
      antibodies in ELISA.
AB  - The major problem associated with ELISA of serum antiganglioside antibodies is
      the high background values (absorbancy of sera added to wells without
      ganglioside), which interfere with the accurate assessment of the fine
      specificity and sensitivity of these antibodies. This investigation identifies
      factors elevating the background values and/or decreasing the fine specificity,
      and describes strategies to minimize their influence. Using sera of neuropathy
      and melanoma patients, we found that highest background values were observed with
      the polystyrene 'tissue culture' microtiter plates; of the various 'non-tissue
      culture' microtiter plates tested, the lowest background values (> 0.060) were
      observed with Costar-3590 (H), Immunolon-3, Immunolon-1, Falcon-3915 (in
      increasing order). Background artifact of polystyrene microtest plates was
      significantly reduced by gamma irradiation (at 40 kRad) and/or use of detergent
      Tween-20 (0.1%) in the washing step. Even after controlling the background
      values, the fine specificity, namely, the ability of the antibody to distinguish
      between the target epitope of an antigen and epitopes of related antigens (when
      moles of antigen/well is constant) varied with different microtiter plates. Using
      sera with high affinity and specificity for GM2, GD3 or GM3, we observed that
      Immunolon-1, Immunolon-3 and particularly Falcon-3915 were superior for assessing
      the abilities of the antibodies to distinguish closely related epitopes found on
      other gangliosides. The reactivity of antiganglioside antibodies was more
      consistent after detergent treatment. The reactivity of antibodies to GD3 is
      significantly enhanced after treatment with Tween-20, but that of antibodies
      reacting to GM1 and GM2 is reduced. Fine specificity of the antiglycolipid
      antibodies was resolved better by coating glycolipids in mol/well rather than by
      weight/well. Based on these results, a protocol for a sensitive and reproducible
      ELISA for serum antiganglioside antibodies is recommended. The protocol takes
      into consideration the suitability of polystyrene plates, coating based on the
      number of molecules, pertinency of the solvent for coating, use of human serum
      albumin for blocking, dilution and washing steps and use of 0.1% Tween-20 to
      further minimize the background absorbancy.

PMID- 7510762
TI  - Separation of complexes of major histocompatibility class II molecules and known
      antigenic peptide by metal chelate affinity chromatography.
AB  - A small fraction of affinity-purified MHC class II molecules are known to bind
      antigenic peptides in vitro. No simple method with acceptable recovery exists for
      separation of complexes of a known antigenic epitope and MHC class II from empty
      MHC class II and complexes of MHC class II and endogenously bound peptide. Here
      we describe an one step metal chelate affinity chromatography method to purify
      complexes of MHC class II and antigenic peptide of known composition. Complexes
      of human HLA-DR2 (DRB1*1501/DRB5*0101) and a peptide analog from human myelin
      basic protein MBP(84-102) containing a 6 histidine tag (6 x His) and a tyrosine
      residue at the N-terminus end [6 x His-MBP(83-102)Y83] were prepared and
      purified. The absence of residual free 6 x His-MBP peptide in the complex
      preparations were confirmed by gel filtration and TLC analyses. The purified
      complexes were applied onto Ni2+.nitrilotriacetic acid (Ni2+.NTA)-agarose
      affinity support and 6 x His-tagged peptide class II complexes were selectively
      eluted with imidazole-containing buffer. The quantitation of bound peptide in the
      eluted complexes showed 100% occupancy of HLA-DR2 (DRB1*1501/DRB5*0101) with [6 x
      His-MBP(83-102)Y83] peptide with a recovery of 50-75%. The presence of a single
      peptide entity in the eluted complexes was confirmed by reverse-phase narrowbore
      HPLC analysis of the acid-extracted supernatant and by amino acid sequencing
      analyses. As expected, no endogenous polypeptide was detected in the Ni2+.NTA
      eluted complexes when analyzed by two-dimensional IEF gel electrophoresis.
      Finally, we demonstrate that both MBP(84-102) and [6 x His-MBP(83-102)Y83]
      peptides were equally capable of stimulating restricted T cell line in the
      presence of autologous antigen presenting cells (APCs). These results demonstrate
      that metal chelate affinity chromatography can be used to prepare MHC class II
      peptide complexes containing single peptide. Such complexes of class II molecules
      containing known peptide have significant clinical relevance for antigen-specific
      therapy of various autoimmune diseases and may provide better understanding of
      the trimolecular interaction between MHC class II, antigenic peptide and T cell
      receptor (TCR).

PMID- 7510763
TI  - A simple method for isolating alpha 2 macroglobulin-cytokine complexes.
AB  - There is the need for a simple, effective procedure for separating alpha 2
      macroglobulin-cytokine complexes from free cytokine in order that the nature and
      possible immunological significance of cytokine-binding by alpha 2 macroglobulin
      (alpha 2-M) might be further investigated. This presentation describes a method
      which exploits the presence of zinc-binding sites on alpha 2-M which permit the
      isolation of complexes from other proteins by zinc-affinity chromatography.
      Furthermore the method may be used in either a column or batch format.

PMID- 7510764
TI  - MxA gene expression after live virus vaccination: a sensitive marker for
      endogenous type I interferon.
AB  - MxA gene expression is known to be regulated tightly and exclusively by type I
      interferons (IFNs). The kinetics of MxA gene expression was analyzed in
      peripheral blood mononuclear cells from 11 healthy volunteers vaccinated with the
      17-D strain of yellow fever virus. A reliable induction of MxA RNA and MxA
      protein was found in the absence of easily detectable serum IFN activity. Thus,
      steady-state MxA RNA levels were elevated 8- to 30-fold above prevaccination
      levels on day 5 after vaccination. The average increase of MxA protein was
      approximately 50-fold. In contrast, no induction of MxA RNA or MxA protein was
      detectable in 3 similarly vaccinated controls who were immune because of previous
      vaccinations. The IFN marker 2'-5'-oligoadenylate (2-5A) synthetase known to
      react to both type I and type II IFNs showed a similar response but did not
      differentiate equally well between nonimmune and immune vaccinees. beta 2
      microglobulin and neopterin reacted poorly, remaining at low levels within the
      normal range. These results demonstrate that MxA gene expression is a good marker
      for detecting minute quantities of biologically active type I IFN during viral
      infections.

PMID- 7510765
TI  - Hemorrhagic fever with renal syndrome: relationship between pathogenesis and
      cellular immunity.
AB  - After phenotype analysis of peripheral blood mononuclear cells (PBMC), soluble
      interleukin-2 receptor (sIL-2R) levels in plasma or sera from patients with
      hemorrhagic fever with renal syndrome (HFRS) were measured. The results showed
      the ratio of activated antigen (CD25, TLiSA1, CD71, and Ia)-positive lymphocytes
      of PBMC in the acute phase of HFRS was higher than that in convalescent phase.
      Moreover, there was much higher expression of heteromorphologic lymphocytes than
      of small lymphocytes. Decreases in T lymphocytes and CD4:CD8 ratios were seen
      with increases in B lymphocyte ratios and interferon-gamma (IFN-gamma) expression
      on PBMC surfaces in the acute phase of HFRS. IFN-gamma-positive lymphocytes
      included CD4, CD8, and CD56 subsets. sIL-2R levels were much higher in sera and
      plasma in the acute phase, especially the oliguric phase. These findings suggest
      that patients with HFRS are in a state of high-level cellular immune response,
      which may be involved in the development of inflammation and pathologic lesions.

PMID- 7510766
TI  - Antibody response to B cell epitopes of Chlamydia trachomatis 60-kDa heat-shock
      protein and corresponding mycobacterial and human peptides in infants with
      chlamydial pneumonitis.
AB  - To study antibody response to the hypersensitivity protein B of Chlamydia
      trachomatis, also known as the 60-kDa heat-shock protein (hsp60), epitope
      scanning was done over the entire protein. Human sera with antibodies to C.
      trachomatis identified 5 major antigenic regions (peptides 2, 5, 9, 17, and 21)
      and several minor regions (peptides 34-37, 39, 50, and 59-62). Clear-cut IgG
      antibody responses to chlamydial peptide 2 (YNEEARKKIQKGVKT) and a corresponding
      mycobacterial peptide (YDEEARRGLERGLNA) were found in 8 of 16 infants with
      chlamydial pneumonitis and in 1 of 18 controls. Peptide 50 (RLAKLSGGVAVIRVG)
      showed an 80% identity with its human counterpart (RLAKLSDGVAVLKVG), which was
      derived from human mitochondrial protein P1, but specific antipeptide antibody
      responses were found in 3 of 16 cases only. In summary, both IgG antibody
      response to C. trachomatis hsp60 and occasional autoantibody formation in infants
      with chlamydial pneumonitis were found.

PMID- 7510768
TI  - Effect of fasting on serum insulin-like growth factor-I (IGF-I) levels and IGF-I
      binding activity in cockerels.
AB  - White Leghorn male chicks of 40 days of age were fasted for 5 days and then
      refed. Blood samples were collected from these chicks before, during and after
      fasting and serum levels of GH and insulin-like growth factor-I (IGF-I) and serum
      IGF-I-binding activity were determined. The fasting-induced reduction in body
      weight was accompanied by a significant rise in circulating GH and fall in IGF-I,
      coupled with increased serum IGF-I-binding activity. When pooled serum was
      chromatographed under neutral conditions, IGF-I binding activity and IGF-I
      immunoreactivity were mainly associated with a large (M(r) = 150,000) and a small
      protein (M(r) = 30,000). Fasting induced a marked increase in the IGF-I-binding
      activity of the 30 kDa IGF-I-binding protein (IGFBP) and refeeding restored
      activity to the normal levels seen before fasting. Ligand blotting of serum
      binding proteins with 125I-labelled IGF-I, after first subjecting the samples to
      polyacrylamide gel electrophoresis and transfer to nitrocellulose, revealed that
      four IGFBPs (M(r) = 20,000, 30,000, 35,900 and 41,000) were present in chicken
      serum, and that the 125I-labelled IGF-I binding of the 30 kDa monomer was
      increased by fasting and restored to normal by refeeding in agreement with gel
      filtration profiles of IGF-I-binding activity. Western blot analysis suggested
      that the 30 kDa IGFBP is homologous to IGFBP-2 found in mammalian blood plasma.
      The results show that IGFBPs in chicken serum and their responses to fasting are
      similar to those in mammals.

PMID- 7510769
TI  - Effects of growth hormone and an antiserum to rat growth hormone on serum IGF-I
      and muscle protein synthesis and accretion in the rat.
AB  - Rats were injected twice daily for up to 10 days with GH or with a polyclonal
      antiserum to rat GH, commencing at 21-22 days of age. Administration of bovine or
      human GH (1mg/day) improved whole body growth rates by 22% and 29% respectively.
      Plantaris muscle mass was also increased, by 7 and 14% respectively. Anti-GH
      injected twice daily resulted in a 7% decrease in body weight at 4 days and a 10%
      reduction by 10 days. Similar decreases were observed in the total protein
      content of plantaris and soleus muscles. The decrease in the fractional rate of
      protein synthesis was proportionately greater than the decline in protein content
      in plantaris muscle whereas in the soleus no change in the rate of protein
      synthesis was observed, suggesting that the effect on this muscle was due to an
      increase in the rate of protein degradation. Serum total IGF-I was unchanged by
      treatment with either GH or anti-GH while the amount of hepatic IGF-I mRNA was
      also unaffected by anti-GH injection. These data are consistent with a direct
      effect of GH or an effect mediated by an autocrine/paracrine mechanism of action
      on muscle but do not support a role for serum total IGF-I as an endocrine
      mediator of GH action.

PMID- 7510767
TI  - Effect of polycations on permeability of glomerular epithelial cell monolayers to
      albumin.
AB  - Polycations can interact with the surface negative charges of the glomerular
      epithelial cells in the kidney and give rise to metabolic alterations. This study
      examined whether charge neutralization can affect intercellular junctions and
      increase macromolecular permeability across epithelial monolayers. We examined
      this question by studying the effect of polycations on the leakage of albumin
      across monolayers of glomerular epithelial cells. Cells were grown to confluency
      on filter-lined cups. They were treated apically with cationic bovine gamma
      globulin or protamine (100 micrograms/ml) for 2 hours at 37 degrees C. After
      washing the cells, the monolayers were tested for leakage of albumin by the
      addition of radioactive bovine serum albumin on the apical side and determining
      the time course of its appearance on the basal side. Polycation treatment caused
      significant leakage of albumin in the absence of any toxic effect on viability or
      lactate dehydrogenase release. The leakage was shown to be through the tight
      junctions of the monolayer. Permeability alterations were compared at 4 degrees C
      and 37 degrees C to determine whether impairment was due to the membrane ruffling
      effect of charge neutralization or due to intracellular metabolic changes.
      Despite equal bindings of polycations at 4 degrees C and 37 degrees C,
      significant leak occurred only at 37 degrees C, suggesting the role of active
      processes in the maintenance of permselectivity. This was consistent with the
      rapid interiorization of the polycation at 37 degrees C after membrane binding.
      Further substantiation of this point was obtained by studying the protective
      effect of removing bound polycation with heparin. Removal of polycation after
      initial binding failed to protect the monolayer from albumin leakage. The
      conclusion was that neutralization of glomerular epithelial cell surface charges
      results in subtle impairment of tight junction control of permeability to
      macromolecules across the monolayer. The impairment was due to active
      intracellular processes that ensue after polycation binding to cell surface
      charges and their subsequent internalization.

PMID- 7510771
TI  - Interaction of monoclonal antibodies with growth hormone-binding protein and its
      complex with growth hormone.
AB  - The properties of four independent lines of monoclonal antibodies (MAbs) specific
      to rat GH-binding protein (GHBP) were examined. Three MAbs, designated GHR-12,
      GHR-13 and GHR-16, were raised against the entire GHBP molecule. The fourth MAb,
      designated as GHBP4.3, was raised against the 17 amino acid residues at the C
      terminal end of rat GHBP. The interaction of these antibodies with GHBP and their
      effect on GH binding to GHBP were analysed by conventional competition binding
      assays and surface plasmon resonance, i.e. with a Biospecific Interaction
      Analysis (BIAcore) instrument. The binding affinity of these MAbs to GHBP ranged
      from 29 nmol/l to 30.9 pmol/l. The pair-wise antibody binding to GHBP on BIAcore
      suggested that GHR-13 and GHR-16 recognized different antigenic determinants
      while part of the GHR-12 epitope might be shared with the other antibodies. The
      antibodies inhibited the interaction of GH with GHBP in the competition binding
      assay. However, in sequential binding on the BIAcore instrument, they were able
      to bind GHBP after its interaction with GH, indicating that the inhibition
      observed in the competition binding assay resulted from steric hindrance rather
      than direct interference with the GH-binding site of GHBP. The present findings,
      therefore, suggest that these antibodies are useful for investigating GHBP and
      its interaction with GH.

PMID- 7510772
TI  - Molecular heterogeneity of the beta-core fragment of human chorionic
      gonadotrophin.
AB  - We have analysed the structure and composition of the beta-core fragment of human
      chorionic gonadotrophin (beta C-hCG) from fresh urine specimens obtained from
      pregnant women and compared our findings with those previously proposed by other
      groups using different protocols. SDS-PAGE separation of reduced beta C-hCG
      demonstrated two major bands with apparent molecular weights of M(r) 8900 and
      M(r) 7500. The molecular weight of the agalacto beta C-hCG was estimated to be
      M(r) 10,218 from the amino acid analysis after high-performance liquid
      chromatography (HPLC) separation. Moreover, HPLC separation of its reduced and S
      carboxymethylated peptides resulted in three peaks, but only two of them could be
      sequenced and demonstrated to be the previously reported beta 6-40 (M(r) 5000)
      and beta 55-92 (M(r) 5300) peptides of the beta hCG subunit. The results showed
      that 56-78% of beta C-hCG molecules of molecular weight M(r) 12,800 were able to
      bind Concanavalin A (Con A). While most were lacking all the peripheral
      monosaccharides and terminated in mannose, some retained other sugar residues on
      their antennae. Direct carbohydrate analysis showed the following molar content
      normalized to six mannose molecules: galactose 2.8, glucosamine 5.3,
      galactosamine 0.3, fucose 1.7 and sialic acid 3.0. Approximately 22-44% of the
      beta C-hCG molecules did not bind Con A (Con A non-reactive forms), of which 88%
      were totally deprived of sugar units and had an apparent molecular weight of
      approximately M(r) 10,000, and 12% were weakly reactive to Con A and reactive to
      anion exchange (negatively charged forms), being incompletely trimmed of their
      oligosaccharide chains. Comparison of our results with those of two other groups
      have indicated that the differences noted among preparations are due to either
      the source or the methods used to purify and characterize this fragment. In
      addition, our results showed significant microheterogeneity on the N-linked
      oligosaccharide moieties with some molecules apparently having no sugar
      molecules. These results have implications for the origins of beta C-hCG,
      suggesting secretion of some molecules without sugar chains and in other cases
      possible metabolism of hCG in the peripheral tissues.

PMID- 7510770
TI  - Regulation of metabolic water and protein compartments by insulin-like growth
      factor-I and testosterone in growth hormone-deficient lit/lit mice.
AB  - Insulin-like growth factor-I (IGF-I) and testosterone are major hormonal
      regulators of protein metabolism. We chose genetically GH-deficient little
      (lit/lit) mice to test whether these anabolic hormones act independently or in
      concert with each other to stimulate protein metabolism. Hormones were
      administered for 14 days at constant rates to 14-week-old lit/lit female mice,
      IGF-I was infused via mini-osmotic pumps at 30 micrograms/day and testosterone
      was administered using 30 mg pellets. Food consumption was measured during the
      experimental period, and at the end we measured: (a) serum IGF-I, IGF-I-binding
      proteins (IGFBPs) and blood urea nitrogen (BUN); (b) body and musculo-skeletal
      carcass weights; (c) musculo-skeletal carcass water, fat, protein and mineral;
      and (d) selected organ weights plus protein and DNA contents. We found that both
      of these growth-stimulatory hormones, IGF-I and testosterone, alone and in
      combination, had anabolic effects on different metabolic compartments in specific
      target organs. The most unexpected finding in this study was that the IGF-I
      induced increase in musculo-skeletal carcass weight arose solely from increased
      water, revealing the importance of this compartment as an early target of IGF-I
      action. Other effects caused specifically by IGF-I, but not testosterone,
      included increases in serum IGFBP-3, body weight and spleen weight. The specific
      effect of testosterone, but not IGF-I, was to increase serum IGFBP-2. Independent
      effects were induced by each hormone alone for kidney and spleen weight, kidney
      and spleen protein content and BUN.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510773
TI  - Block by ruthenium red of the ryanodine-activated calcium release channel of
      skeletal muscle.
AB  - The effects of ruthenium red and the related compounds tetraamine palladium
      (4APd) and tetraamine platinum (4APt) were studied on the ryanodine activated
      Ca2+ release channel reconstituted in planar bilayers with the immunoaffinity
      purified ryanodine receptor. Ruthenium red, applied at submicromolar
      concentrations to the myoplasmic side (cis), induced an all-or-none flickery
      block of the ryanodine activated channel. The blocking effect was strongly
      voltage dependent, as large positive potentials that favored the movement of
      ruthenium red into the channel conduction pore produced stronger block. The half
      dissociation constants (Kd) for ruthenium red block of the 500 pS channel were
      0.22, 0.38, and 0.62 microM, at +100, +80, and +60 mV, respectively. Multiple
      ruthenium red molecules seemed to be involved in the inhibition, because a Hill
      coefficient of close to 2 was obtained from the dose response curve. The half
      dissociation constant of ruthenium red block of the lower conductance state of
      the ryanodine activated channel (250 pS) was higher (Kd = 0.82 microM at +100
      mV), while the Hill coefficient remained approximately the same (nH = 2.7).
      Ruthenium red block of the channel was highly asymmetric, as trans ruthenium red
      produced a different blocking effect. The blocking and unblocking events (induced
      by cis ruthenium red) can be resolved at the single channel level at a cutoff
      frequency of 2 kHz. The closing rate of the channel in the presence of ruthenium
      red increased linearly with ruthenium red concentration, and the unblocking rate
      of the channel was independent of ruthenium red concentrations. This suggests
      that ruthenium red block of the channel occurred via a simple blocking mechanism.
      The on-rate of ruthenium red binding to the channel was 1.32 x 10(9) M-1 s-1, and
      the off-rate of ruthenium red binding was 0.75 x 10(3) s-1 at +60 mV, in the
      presence of 200 nM ryanodine. The two related compounds, 4APd and 4APt, blocked
      the channel in a similar way to that of ruthenium red. These compounds inhibited
      the open channel with lower affinities (Kd = 170 microM, 4APd; Kd = 656 microM,
      4APt), and had Hill coefficients of close to 1. The results suggest that
      ruthenium red block of the ryanodine receptor is due to binding to multiple sites
      located in the conduction pore of the channel.

PMID- 7510774
TI  - Structural features of myelin basic protein mRNAs influence their translational
      efficiencies.
AB  - The myelin basic protein (MBP) gene expresses several alternatively spliced
      products with the same 5' and 3' untranslated regions (UTRs). It has been
      reported that its expression may be regulated not only at the transcriptional
      level but also at the translational level during development. We engineered
      several MBP mRNA deletion mutants with 5' (-48, -37, -27, -22, and -10) and 3'
      UTRs of differing lengths and examined the translational efficiencies of these
      constructs in cell-free systems. The translational efficiencies of the constructs
      differed significantly over a range of almost 10-fold. A deletion of 11
      nucleotides from the 5' end of the natural (i.e., -48) MBP mRNA resulted in an
      approximate fourfold reduction in translational efficiency. Further truncation of
      the 5' UTR increased the translational efficiencies of the constructs as has been
      observed with many RNAs. These results suggest that there may be a positive
      control element between -48 and -37 nucleotides in the 5' UTR of MBP mRNA. The
      effects of modifying the lengths of the 5' UTR on the translational efficiency of
      mRNAs encoding the 21.5-kDa and 14-kDa MBPs were the same, suggesting that the
      effect observed was not unique to the 21.5-kDa MBP mRNA. Truncating the 3' UTR of
      four different alternatively spliced MBP mRNAs also altered their translational
      efficiencies. Thus, the 5' and 3' UTRs of MBP mRNAs appear to influence the
      translation of these mRNAs, and such factors may be involved in the translational
      regulation of MBP gene expression.

PMID- 7510775
TI  - Expression and effects of hyaluronan and of the hyaluronan-binding protein
      hyaluronectin in newborn rat brain glial cell cultures.
AB  - Hyaluronan (HA) is a polymerized nonsulfated extracellular matrix
      glycosaminoglycan that may be involved in brain development. We have tested the
      expression of HA and the HA-binding protein hyaluronectin (HN) in glial cell
      cultures from newborn rat brain. HA was secreted into the culture medium by type
      1 astrocytes in the first stages of the primary cultures. The secretion was high
      during cell proliferation, reached a maximum when they were confluent, and then
      decreased. HA was not secreted at a detectable level by total O-2A lineage cell
      enriched cultures. HA labeled small O-2A progenitor cells (GFA-, A2B5+, HA+),
      small O-2A progenitorlike (GFA-, A2B5-, HA+) cells, and type 2 astrocytes (GFA+,
      A2B5+, HA+), but not mature oligodendrocytes (Galc+, HA-). In contrast to HA,
      hyaluronectin labeled oligodendrocyte membranes (i.e., more mature cells) from
      day 8. A2B5+ GFA- cells were found to be either HA+ or HN+ at days 7-9,
      suggesting intermediary stages. The addition of HA to primary cultures and to O
      2A progenitor-enriched cultures decreased significantly the increase in the
      number of O-2A progenitors, of mature (Galc+) oligodendrocytes proportionally to
      the decrease of the O-2A progenitor number, and of BrdU+ cells, suggesting that
      HA acts (directly or indirectly) on O-2A cell proliferation. This effect, which
      was seen for concentrations as low as 0.1 micrograms/ml, was HA specific and was
      not observed with other glycosaminoglycans. When primary cultures were performed
      in the presence of hyaluronidase-digested or HA-depleted (by passage on a HN
      column) fetal calf serum, the total number of O-2A lineage cells was dramatically
      increased (100%, p < 10(-4)) in comparison with control cultures in standard
      fetal calf serum. Platelet-derived growth factor increased the total number of O
      2A lineage cells and of (Galc+) oligodendrocytes. This effect was opposed by HA
      dose dependently. The effect of HA was significantly inhibited by HN (30%, p <
      10(-4)). HN had, however, no effect when it was added to culture in the presence
      of hyaluronidase in fetal calf serum, suggesting its effect was only due to its
      binding to HA. During cell maturation, HA disappears as HN appears. This and the
      fact that HA and PDGF have opposite effects suggest an effect of these factors,
      or of their balance, on myelination.

PMID- 7510776
TI  - A novel inhibitory role for glucocorticoids in the secretion of angiotensinogen
      by C6 glioma cells.
AB  - Astrocytes have been identified as the primary source of brain angiotensinogen
      (Ao), but the regulation of the secretion of this protein from astrocytes is
      poorly defined. In this study, the rat C6 glioma cell line was used as an
      astrocyte model to investigate the regulation of Ao secretion. C6 cultures
      secreted Ao at a rate of 4.05 +/- 1.52 (mean +/- SD) ng of Ao/10(6) cells/24 h as
      determined by a direct radioimmunoassay. This rate was not significantly altered
      by the hormones thyroxine, estradiol, angiotensin II, growth hormone, and
      prostaglandins or by increased levels of intracellular cyclic AMP. Treatment with
      the synthetic glucocorticoid dexamethasone (DEX; 10(-6) M) reduced the rate of Ao
      secretion to 1.82 +/- 0.28 ng of Ao/10(6) cells/24 h. By comparison, the basal
      secretion rate for rat H4 hepatoma cells was 142.4 +/- 10.0 ng of Ao/10(6)
      cells/24 h, and this increased fourfold (572.4 +/- 173.1 ng/10(6) cells/24 h) in
      the presence of 10(-6) M DEX. Both these inhibitory (C6) and stimulatory (H4)
      actions of DEX were dose related. The inhibition observed in C6 cells was
      mimicked by RU28362, a pure glucocorticoid agonist, and reversed by the
      antagonist RU486, demonstrating that DEX was functioning as a true
      glucocorticoid. The action of DEX was also antagonized by the cyclic AMP analogue
      N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dBcAMP) (control, DEX, and
      DEX + dBcAMP, 3.58 +/- 0.73, 1.69 +/- 0.82, and 4.93 +/- 1.88 ng of Ao/10(6)
      cells/24 h, respectively, and by the beta-adrenergic agonist isoprenaline, which
      stimulates cyclic AMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510777
TI  - Staurosporine, K-252a, and K-252b stabilize calcium homeostasis and promote
      survival of CNS neurons in the absence of glucose.
AB  - Staurosporine, K-252a, and the 9-carboxylic related compound K-252b are low
      molecular-weight alkaloids from microbial origin that at high concentrations are
      kinase inhibitors and can antagonize the effects of neuronal growth factors.
      Paradoxically, we have found that very low concentrations of these agents (10 fM
      10 nM) prolong the survival of hippocampal, septal, and cortical neurons deprived
      of glucose. These agents did not prevent the depletion of ATP caused by glucose
      deprivation. The large elevation of intracellular calcium levels that normally
      mediates glucose deprivation-induced damage was attenuated by staurosporine, K
      252a, and K-252b. Western blot analysis using antiphosphotyrosine antibody showed
      that staurosporine and the K-252 compounds (10-100 pM) stimulated tyrosine
      phosphorylation of several different proteins. The tyrosine kinase inhibitor
      genistein significantly reduced the protective effect of staurosporine and the K
      252 compounds, indicating that tyrosine phosphorylation was required for
      neuroprotection by these compounds. Taken together, the data demonstrate that low
      concentrations of staurosporine and the K-252 compounds can stabilize calcium
      homeostasis, possibly by a mechanism involving activation of receptor tyrosine
      kinase transduction pathways.

PMID- 7510780
TI  - SR 140333, a novel, selective, and potent nonpeptide antagonist of the NK1
      tachykinin receptor: characterization on the U373MG cell line.
AB  - The effects of a novel nonpeptide NK1 tachykinin receptor antagonist, SR 140333,
      on the functional consequences of NK1 receptor activation in a human astrocytoma
      cell line, U373MG, were investigated. Radioligand binding conducted with 125I
      Bolton-Hunter substance P revealed a competitive inhibition by SR 140333 and its
      R enantiomer SR 140603 with Ki values of 0.74 and 7.40 nM, respectively. The NK1
      selective agonist, [Sar9,Met(O2)11]-substance P, stimulated the formation of
      inositol phosphates with an EC50 of 3.8 x 10(-9) M. SR 140333 blocked the
      stimulatory effect of this agonist (10(-7) M) with an IC50 of 1.6 x 10(-9) M,
      whereas the effect of another NK1 agonist, septide (EC50 = 1.5 x 10(-8) M) was
      antagonized with an IC50 of 2.1 x 10(-10) M. Enhancement of [3H]taurine release
      by [Sar9,Met(O2)11]-substance P (EC50 = 7.4 x 10(-9) M) was also inhibited by SR
      140333 with an IC50 of 1.8 x 10(-9) M. SR 140603 was 10-fold less potent than SR
      140333 in inhibiting inositol monophosphate formation and [3H]taurine release.
      The calcium mobilization induced by [Sar9,Met(O2)11]-substance P (10(-8) M) was
      totally prevented by 10(-8) M SR 140333. Patch-clamp experiments showed that SR
      140333 depressed the outward current evoked by 5 x 10(-8) M [Sar9, Met(O2)11]
      substance P with an IC50 of 1.3 x 10(-9) M. The expression of c-fos was
      stimulated by [Sar9,Met(O2)11]substance P with an EC50 of 2.5 x 10(-10) M, an
      effect that was also inhibited by SR 140333 with an IC50 of 1.1 x 10(-9)
      M.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510778
TI  - Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and interleukin-6 but
      not TNF-beta induce differentiation of neuroblastoma cells: the role of nitric
      oxide.
AB  - Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and
      interleukin-6 (IL-6), but not TNF-beta, can induce the in vitro differentiation
      of the neuroblastoma cell line N103 in a dose-dependent manner. Differentiation
      of N103 was accompanied by the arrest of cell growth and neurite formation. The
      induction of neuroblastoma cell differentiation by TNF-alpha and IFN-gamma can be
      specifically inhibited by a nitric oxide (NO) synthase inhibitor, L-NG
      monomethylarginine. In contrast, the differentiation of N103 cells by IL-6 was
      not affected by L-NG-monomethylarginine. These results indicate that TNF-alpha
      and IFN-gamma, but not IL-6, induce the differentiation of neuroblastoma cells
      via NO. This is confirmed by the finding that the culture supernatants of N103
      cells induced by TNF-alpha and IFN-gamma, but not that by IL-6, contained high
      levels of NO2-, the production of which was inhibited by L-NG-monomethylarginine.
      Furthermore, the differentiation of N103 cells can be induced directly in a dose
      dependent manner by the addition of nitroprusside, a generator of NO, into the
      culture medium. These data therefore indicate that NO may be an important
      mediator in the induction of neuronal cell differentiation by certain cytokines
      such as TNF-alpha and IFN-gamma and that neuronal cells, in addition to the
      macrophage-like brain cells, can be induced by immunological stimuli to produce
      large quantities of NO.

PMID- 7510781
TI  - Effects of ion channel blockers and phorbol ester treatments on [3H]dopamine
      release and neurotensin facilitation of [3H]dopamine release from rat
      mesencephalic cells in primary culture.
AB  - In this work, we tested the effect of ion channel blockers and of phorbol ester
      treatments on [3H]dopamine ([3H]DA) release and neurotensin (NT)-induced
      facilitation of [3H]DA release from cultures of rat fetal mesencephalic cells.
      The potassium channel blockers tetraethylammonium and 4-aminopyridine increased
      basal [3H]DA release and decreased K(+)-evoked [3H]DA release, whereas apamin was
      without effect. K(+)-evoked [3H]DA release was decreased by omega-conotoxin and
      nifedipine, totally suppressed by cadmium, and unaffected by amiloride. These
      results show the differential sensitivity of [3H]DA release to blockade of
      various ion channels and suggest the involvement of N-type, L-type, and non-L-non
      N-type, but not T-type, voltage-sensitive calcium channels in K(+)-evoked
      release. Phorbol 12-myristate 13-acetate increased both spontaneous and K(+)
      evoked [3H]DA release, suggesting a modulatory action of protein kinase C on DA
      release in this system. Unexpectedly, however, the effects of the phorbol ester
      were not counteracted by the protein kinase C inhibitors H7, staurosporine, or
      polymyxin B. NT-induced facilitation of K(+)-evoked [3H]DA release was
      insensitive to most of the ion channel blockers, except cadmium (64% decrease in
      NT effect), suggesting that the corresponding potassium and calcium channels were
      not involved in the effect of NT on [3H]DA release in this system. The NT effect
      was totally suppressed by phorbol ester treatments, indicating a possible
      desensitization of the corresponding transduction mechanisms after protein kinase
      C activation.

PMID- 7510782
TI  - Effect of probe size on the concentration of brain extracellular uric acid
      monitored with carbon paste electrodes.
AB  - We have investigated further the anomalously high concentration of brain
      extracellular uric acid detected with in vivo sampling probes reported recently.
      The contribution by uric acid and 5-hydroxyindoleacetic acid (5-HIAA) to peak 2
      recorded in rat striatum with chronically implanted carbon paste electrodes
      (CPEs) of different sizes was estimated by comparing peak current densities and
      the effect of the monoamine oxidase inhibitor pargyline. The concentration of
      uric acid in the extracellular fluid was some 50 times greater for 320-microns
      diameter CPEs than for 160-microns-diameter electrodes, where the urate level was
      estimated at approximately 1 microM. The concentration of 5-HIAA was similar for
      320-, 260-, and 160-microns-diameter CPEs. These data provide an explanation for
      the previously observed differences in 5-HIAA/urate ratios recorded with 320
      microns-diameter CPEs and smaller carbon fibre electrodes. The results also
      indicate that chronically implanted sampling probes of diameter > 160 microns
      perturb the surrounding tissue, which produces uric acid by a mechanism yet
      unknown, although preliminary histological data suggest that glial cells may be
      involved.

PMID- 7510779
TI  - Tyrosine phosphorylation and activation of mitogen-activated protein kinase in
      the rat brain following transient cerebral ischemia.
AB  - Activation of trophic factor receptors stimulates tyrosine phosphorylation on
      proteins and supports neuronal survival. We report that in the recovery phase
      following reversible cerebral ischemia, tyrosine phosphorylation increases in the
      membrane fraction of the resistant hippocampal CA3/dentate gyrus (DG) region,
      whereas in the sensitive CA1 region or striatum, tyrosine phosphorylation is less
      marked or decreases. In the cytosolic fractions, a 42-kDa protein, identified as
      mitogen-activated protein (MAP) kinase, is markedly phosphorylated and activated
      immediately following ischemia, in particular in CA3/DG, but not in striatum. In
      the CA1 region, phosphorylation of MAP kinase is less intense and decreases later
      during reperfusion, which could explain the delay of neuronal degeneration in
      this structure. The data suggest that in ischemia-resistant neurons the growth
      factor receptor-coupled signaling cascade is stimulated and, through its effects
      on DNA transcription and mRNA translation, supports neuronal survival.

PMID- 7510783
TI  - Galanin-like immunoreactivity is increased in the postmortem cerebral cortex from
      patients with Alzheimer's disease.
AB  - Galanin is a peptide that is associated with cholinergic neurons of the basal
      forebrain, and, thus, of interest for the neuropathology of Alzheimer's disease.
      In the present study, human galanin-like immunoreactivity was measured in
      postmortem human cerebral cortical tissues by using a homologous
      radioimmunoassay. In an initial study, six cerebral cortical regions were
      evaluated from nine elderly controls, 13 neuropathologically verified Alzheimer's
      disease patients, and 19 elderly schizophrenics. A significant 65% increase in
      galanin was found in frontal cortex Brodmann area 8 of Alzheimer's disease
      patients compared with controls. In contrast, cerebral cortical tissues from
      elderly schizophrenics were not different from those from elderly controls in any
      region. In a second study, 10 cerebral cortical regions were evaluated from 50
      neuropathologically verified Alzheimer's disease patients and nine elderly
      controls. Concentrations of galanin were increased significantly 26-61% in six of
      10 cerebral cortical regions examined (Brodmann areas F8, F44, T20, T21, T36, and
      P22). Purification of brain extracts by size-exclusion Sephadex G-50
      chromatography revealed that human galanin-like immunoreactivity eluted in two
      peaks of different molecular weights. These studies reveal increased
      concentrations of galanin in the cerebral cortex of Alzheimer's disease, similar
      to previous findings in basal forebrain tissue. Because galanin inhibits
      cholinergic neurotransmission, these findings may have important implications in
      the understanding of Alzheimer's disease neuropathology and associated cognitive
      deficits.

PMID- 7510784
TI  - Subcellular localization and characterization of neuronal nitric oxide synthase.
AB  - In contrast to the predominantly particulate, Ca2+/calmodulin-dependent nitric
      oxide (NO) synthase in endothelial cells, the corresponding neuronal isoenzyme is
      considered to be mainly soluble, presumably owing to the lack of a
      posttranslational myristoylation. However, preliminary findings from this and
      other laboratories suggest that a substantial portion of the neuronal NO synthase
      activity may in fact be membrane bound. We have therefore investigated the
      distribution of this enzyme among subcellular fractions of the rat and rabbit
      cerebellum in more detail. Up to 60% of the total NO synthase activity was found
      in the particulate fraction and, according to density gradient
      ultracentrifugation, associated mainly with the endoplasmic reticulum fraction.
      There was no apparent difference between the soluble and particulate enzymes with
      respect to their specific activity, Ca2+ and pH dependency, inhibitor
      sensitivity, or immunoreactivity, suggesting that both rat and rabbit cerebella
      contain a single Ca2+/calmodulin-dependent NO synthase. The inhibition by the
      cytochrome P450 inhibitor SKF-525A of the NO synthase activity in these
      subcellular fractions (IC50 = 90 microM) and the fact that mammalian cytochrome
      P450 enzymes are endoplasmic reticulum-bound proteins support the notion that the
      cerebellar NO synthase is a cytochrome P450-type hemoprotein. Moreover, the
      aforementioned findings suggest that posttranslational myristoylation may not be
      the only factor determining the intracellular localization of NO synthase.

PMID- 7510785
TI  - Protein kinase FA/glycogen synthase kinase-3 predominantly phosphorylates the in
      vivo site Thr97-Pro in brain myelin basic protein: evidence for Thr-Pro and Ser
      Arg-X-X-Ser as consensus sequence motifs.
AB  - In a previous study, protein kinase FA/glycogen synthase kinase-3 (FA/GSK-3) was
      identified as a myelin basic protein (MBP) kinase associated with intact brain
      myelin. In this report, the phosphorylation sites of MBP by kinase FA/GSK-3 were
      further determined by two-dimensional electrophoresis/TLC, phosphoamino acid
      analysis, tryptic peptide mapping, Edman degradation, and direct sequencing.
      Kinase FA/GSK-3 phosphorylates MBP on both threonine and serine residues. Three
      tryptic phosphopeptide peaks were resolved by C18 reverse-phase HPLC. Sequential
      manual Edman degradation together with direct sequence analysis revealed that
      T(p)PPPSQGK is the phosphorylation site sequence for the first major
      phosphopeptide peak. When mapping with the bovine brain MBP sequence, we finally
      demonstrate Thr97-Pro, one of the in vivo phosphorylation sites in MBP, as the
      major site phosphorylated by kinase FA/GSK-3, implicating a physiologically
      relevant role of FA/GSK-3 in the regulation of brain myelin function. By using
      the same approach, we also identified NIVT94(p)PR as the phosphorylation site
      sequence in the second major tryptic phosphopeptide derived from [32P]MBP
      phosphorylated by kinase FA/GSK-3, further indicating that kinase FA/GSK-3
      represents a Thr-Pro motif-directed MBP kinase involved in the phosphorylation of
      brain myelin.

PMID- 7510786
TI  - Hexaprenoid hydroquinones, novel inhibitors of the reverse transcriptase of human
      immunodeficiency virus type 1.
AB  - Activity against human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) in the organic extract of the Red Sea sponge Toxiclona toxius
      was traced by us to five novel natural compounds, namely toxiusol [1],
      shaagrockol B [3], shaagrockol C [4], toxicol A [6], all of which are sulfated
      hexaprenoid hydroquinones, and toxicol B [7], the p-hydroquinone derivative of
      compound 6. The hydrolysis of the two sulfated compounds 1 and 4 yielded the
      corresponding hydroquinones designated as compounds 2 and 5, and further
      oxidation of compound 7 afforded the corresponding p-quinone derivative, compound
      8. All compounds exhibited inhibitory activity of both DNA polymerizing functions
      of HIV-1 RT but failed to inhibit the RT-associated ribonuclease H activity.
      Toxiusol [1] was found to be the most potent inhibitor of the RNA-dependent DNA
      polymerase function (with 50% inhibition obtained at 1.5 microM and 95%
      inhibition at 4.6 microM), whereas the DNA-dependent DNA polymerase was
      significantly less sensitive to the inhibitor (with 50% inhibition achieved at
      6.6 microM and 95% inhibition only at 41.6 microM). The fact that compound 1
      discriminates between the two DNA polymerase activities of the RT offers new
      prospects for developing potent and highly specific anti-RT compounds, since the
      RNA-dependent DNA polymerase activity of RT is the only unique function that is
      not expressed at significant levels in uninfected mammalian cells.

PMID- 7510787
TI  - Relative frequency of autoantibodies to myelin basic protein and proteolipid
      protein in optic neuritis and multiple sclerosis cerebrospinal fluid.
AB  - Myelin basic protein (MBP) and proteolipid protein (PLP) were purified from non
      MS human brain and used in solid phase radioimmunoassays to detect their specific
      antibodies in cerebrospinal fluid (CSF) of optic neuritis and clinically definite
      multiple sclerosis (MS) patients. In 53 optic neuritis patients free anti-MBP was
      elevated in 47 and in 6 of these 47 patients bound anti-MBP was also increased.
      The remaining 6 patients with undetectable anti-MBP had increased levels of anti
      PLP in their CSF. None of these optic neuritis patients had autoantibodies to
      both antigens. Of 173 MS patients with acute relapses 169 had increased free anti
      MBP. Three of the 4 remaining patients with undetectable anti-MBP had increased
      anti-PLP in their CSF. Of 110 MS patients with chronic progressive disease, 107
      had increased CSF anti-MBP and 2 had elevated anti-PLP. Of 87 MS patients in
      remission, 15 had modestly elevated anti-MBP and none had detectable anti-PLP.
      Considering the total of 370 clinically definite MS patients with active and
      inactive disease, 77% had increased CSF anti-MBP and 1% had increased CSF anti
      PLP. These findings are suggesting 2 immunochemically distinct forms of MS: a
      common form with autoantibodies directed against MBP and a more rare form
      associated with anti-PLP.

PMID- 7510788
TI  - A standardized protocol for flow cytometric analysis of cells isolated from
      cerebrospinal fluid.
AB  - Flow cytometry (FC) is an useful tool for the analysis of subpopulations in
      complex cell suspensions. When applying this method to the cerebrospinal fluid
      (CSF), some characteristic properties of this cell type must be taken into
      consideration: there are only few cells which decay rapidly in their native
      medium and during centrifugation. One aim of the immunostaining procedure
      preceding flow cytometric analysis must be to minimize cell loss in order to get
      an undistorted picture of 'true' CSF cell populations. Consequently,
      morphological flow cytometric plots of high resolution are an indispensable
      precondition for reliable determination of subpopulations defined by monoclonal
      antibody (Mab) binding. We describe a standardized protocol for the flow
      cytometric examination of CSF cells which minimizes undesired cell loss. By the
      use of a 'quality control' the extent of cell loss could be monitored. Examples
      of morphological flow cytometric plots are given. The subsequent determination of
      Mab binding subpopulations is critical when fluorescence intensities of antigen
      positive and negative cells are non-disjunct. A statistical test was developed
      for these cases often seen when cell surface determinants are expressed at low
      levels only.

PMID- 7510789
TI  - A kinetic study of simultaneous suicide inactivation and irreversible inhibition
      of an enzyme. Application to 1-aminocyclopropane-1-carboxylate (ACC) synthase
      inactivation by its substrate S-adenosylmethionine.
AB  - This paper deals with the development of an experimental method for the kinetic
      study of the inactivation of an enzyme by a racemic mixture of an inhibitor,
      whose isomers operate as suicide substrate and irreversible inhibitor
      respectively. The ratio between the isomer concentration in the biological or
      commercial source must be determined, but no separation of them is required. The
      method involves a kinetic analysis and an experimental design that enables the
      affinity (1/Km), rate of catalysis (kcat), rate of inactivation (lambda max),
      efficiency of catalysis (kcat/Km) and efficiency of inactivation (lambda max/Km)
      to be determined. The method has been applied to the kinetic characterization of
      the inactivation of 1-aminocyclopropane-1-carboxylate (ACC) synthase from tomato
      fruits by its substrate, S-adenosylmethionine (AdoMet). The ratio between AdoMet
      isomers with respect to its sulfonium centre, namely (-)-AdoMet and (+)-AdoMet,
      present in the commercial sample used, has been determined by 1H nuclear magnetic
      resonance.

PMID- 7510791
TI  - Deoxyribonuclease inhibitors produced by streptomycetes.
AB  - Streptomyces sp. strain No. A-5838 produces three types of inhibitors of DNase
      II. Two of them, DNI-2 and DNI-3, were distinguished from the previously reported
      DNase II inhibitors, 5838-DNI and 5923-DNI, by their inhibitory profiles towards
      phosphodiesterases. DNI-2 has M(r) 654, and is considered to be a coproporphyrin.
      DNI-3 is an acidic substance with M(r) about 60,000 as estimated by gel
      filtration. The inhibitory activities of both inhibitors were shown to be
      temperature-dependent whereas only that of DNI-2 was pH-dependent.

PMID- 7510790
TI  - Further evidence for the importance of free carboxylate in epoxysuccinate
      inhibitors of thiol proteases.
AB  - Analogs of Ep-475 (2a), designed to explore the role played by the carboxylate in
      epoxysuccinate thiol protease inhibitors, have been synthesized and tested as
      inhibitors of papain and cathepsin B. Papain and cathepsin B are rapidly
      inactivated by carboxylates 2a and 6a, but are inactivated much more slowly by 2b
      2f, 6c, and 6f, in which the carboxylate is absent or replaced by an amide,
      ester, or ketone. This order of reactivity contrasts with the inherent reactivity
      of substituted epoxides toward a non-enzymatic thiolate, previously shown to
      decrease in the order: COCH3 > CO2CH3 > CONH2 > H > CO2H. The results suggest
      that electrostatic attraction between the carboxylate of the inhibitor and
      protonated His159 of papain facilitates docking of the inhibitor in the active
      site of the enzyme, a conclusion reached previously from X-ray crystallographic
      structures of epoxysuccinates bound to papain. The most reactive isoleucine
      analog, 6a, was significantly less reactive than leucine-containing Ep-475 (2a),
      while the less reactive isoleucine derivatives, 6c and 6f, were similar in
      reactivity to the corresponding leucine derivatives, 2c and 2f, respectively.

PMID- 7510792
TI  - Modulation of 3 alpha-hydroxysteroid dehydrogenase activity by the redox state of
      glutathione.
AB  - 3 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1.50), purified to homogeneity from
      rat liver, was strongly inactivated by incubation with a disulfide such as GSSG,
      L-cystine or L-cystamine, as well as an SH-reagent such as DTNB (5,5'-dithiobis(2
      nitrobenzoic acid)), NEM (N-ethylmaleimide) or iodoacetic acid. The inactivation
      advanced with incubation time. Coenzyme (NADP+) completely protected the enzyme
      from this inactivation by disulfides, but neither of the substrates (androsterone
      and benzenedihydrodiol) did. The activity of inactivated enzyme was restored by
      treatment with thiols such as DTT (dithiothreitol) or GSH. In the GSH/GSSG redox
      buffer, the enzyme existed in an equilibrium between active (reduced) and
      inactive (oxidized) forms.

PMID- 7510793
TI  - The anti-ulcer drug ranitidine hydrochloride and its synthetic intermediates are
      inactivators of monoamine oxidase-B.

PMID- 7510795
TI  - Binding of bovine basic pancreatic trypsin inhibitor (Kunitz) as well as bovine
      and porcine pancreatic secretory trypsin inhibitor (Kazal) to human cathepsin G:
      a kinetic and thermodynamic study.
AB  - The effect of pH and temperature on kinetic and thermodynamic parameters for the
      binding of the bovine basic pancreatic trypsin inhibitor (Kunitz inhibitor; BPTI)
      as well as bovine and porcine pancreatic secretory trypsin inhibitor (Kazal
      inhibitor; bovine and porcine PSTI, respectively) to human cathepsin G (EC
      3.4.21.20) has been investigated. The affinity of the macromolecular inhibitors
      examined for cathepsin G is characterized by an endothermic, entropy-driven,
      behaviour, and shows the following trend: BPTI > bovine PSTI > porcine PSTI. The
      affinity difference of BPTI as well as of bovine and porcine PSTI for cathepsin G
      is mostly accounted for by changes in the values of the apparent dissociation
      rate constant for the proteinase:inhibitor complex destabilization. On increasing
      the pH from 4.5 to 9.5 (at 25.0 degrees C), the affinity of BPTI, as well as
      bovine and porcine PSTI for cathepsin G increases thus reflecting the acidic-pK
      shift of the His-57 catalytic residue from approximately 6.9 in the free enzyme
      to approximately 5.0 in the serine proteinase:inhibitor complexes. The BPTI as
      well as the bovine and porcine PSTI binding properties of cathepsin G have been
      analyzed in parallel with those of related serine (pro)enzyme/macromolecular
      inhibitor systems. Considering the known molecular models, the observed binding
      behaviour of BPTI as well as that of bovine and porcine PSTI to cathepsin G has
      been related to the inferred stereochemistry of the serine proteinase/inhibitor
      contact region(s).

PMID- 7510794
TI  - Inhibition of beta-N-acetylglucosaminidase by glycon-related analogues of the
      substrate.
AB  - Inhibition studies on beta-N-acetylglucosaminidase (EC 3.2.1.30) of widely
      differing origins (animal, plant, fungus) were carried out with N
      acetylglucosaminono-1,5-lactone (1), N-acetylglucosaminono-1,5-lactam (2), 1,5
      imino-N-acetylglucosaminitol (3), and N-acetylglucosaminono-1,5-lactone oxime
      (4). The inhibition was competitive in all cases, and Ki values were generally in
      the range of 0.15-2 microM, except for the fungal enzyme (5-20 microM). To assess
      the kinetics of enzyme-inhibitor complex formation, continuous enzyme activity
      monitoring was done with 3,4-dinitrophenyl-beta-N-acetylglucosaminide as the
      substrate. A slow approach to the binding-equilibrium in the time scale of
      minutes could not be observed with any of the inhibitors tested (1-4). The
      results are evaluated as to the bearing of the enzyme source on best performance
      of the test compounds, the sub-type of inhibition mechanism is discussed, and
      suggestions are made for further analogue syntheses as well as potential
      applications of 1-4 (particularly the O-phenylcarbamoyl derivative of the latter)
      in biological and medical research.

PMID- 7510796
TI  - Affinity preparation of a protein inhibitor recognising a cell surface protease.
AB  - Epithelial cell surfaces possess a trypsin-like protease, referred to as
      guanidinobenzoatase (GB). The cytoplasm of these cells contains an extractable
      protein (I) which recognises the cell surface GB by forming an enzyme-inhibitor
      complex (GB-I). Rhodamine-agmatine (Rh-Agm) was designed as a red fluorescent
      probe, directed to the active centre of GB, which can be used to locate cells
      with GB, employing fluorescence microscopy. Rh-Agm has a high affinity for GB and
      will displace I from GB-I on the surfaces of cells in frozen sections. Rh-Agm has
      been used to displace I from immobilised GB-I complexes on the surface of
      cultured colonic carcinoma cells in an affinity procedure aimed at purifying the
      inhibitors of GB obtained from cultured carcinoma cells. These inhibitors have
      been tested on protected frozen sections of normal colon and carcinoma of the
      colon, the formation of GB-I complexes being followed by a second yellow
      fluorescent probe which competes for the active centre of GB. The study of the
      protein-protein interactions to form GB-I has been facilitated by employing two
      synthetic fluorescent inhibitors of GB with differing affinities for GB and
      different fluorescent properties. The use of sections of tissue in this study has
      enabled a sequence of reactions to be carried out on the same cell surface GB,
      such that reversible inhibition reactions can be quickly demonstrated and
      recorded by fluorescence microscopy.

PMID- 7510797
TI  - A severity index designed as an indicator of acuity in palliative care.
AB  - Patients who are facing terminal illness frequently experience changes in health
      care settings which are necessitated by acute events during palliative care. This
      pilot study evaluates the reliability, criterion validity, and appropriateness of
      the San Diego Severity Index (SDSI) in a population of advanced cancer patients
      in different care settings. The SDSI includes diagnostic, acuity, and
      psychosocial assessments. Cancer patients were evaluated in an outpatient
      oncology clinic (SCRF), a hospice home care (HC) program, and an acute care
      hospital/hospice centre (ACC). Scores were lowest for SCRF (9.51 +/- 3.7), HC was
      intermediate (24.04 +/- 8.8), while patients at the ACC scored the highest (29.33
      +/- 7.0). Patients admitted to the ACC were significantly more acute, as assessed
      by the SDSI, than those utilizing outpatient services. This instrument may be
      useful as an indicator of appropriate transitions between health care settings.

PMID- 7510799
TI  - When the dying demand death.

PMID- 7510798
TI  - Victoria BGY palliative care model--a new model for the 1990s.
AB  - If, as palliative care practitioners, we ensure that distressing symptoms such as
      pain, vomiting, dyspnea, confusion, and pre-death restlessness are fully
      controlled (note "fully"), then most people are deeply appreciative and continue
      to live until they die, confident that whatever happens, their worth, desires,
      and comfort are secure. Credibility (Latin, fides dignus) is remaining true and
      reliable to what was agreed. Patients registering with palliative care generally
      desire comfort, which can only occur when palliative care physicians and programs
      are capable and willing to apply all three types of palliation discussed here-
      the BGY model.

PMID- 7510800
TI  - Metoclopramide-induced extrapyramidal syndromes.

PMID- 7510803
TI  - Music therapy perspectives in palliative care education.
AB  - Major strides have been made in expanding the content of professional education
      in palliative care to include a focus on attitudes which nurture compassionate
      care as well as on knowledge and skills. However, accessing the emotional spheres
      -for instance the fear and helplessness of caregivers--remains a challenge. The
      inclusion of music therapy techniques as a teaching modality, with an emphasis on
      emotional experience and nonverbal expression, is suggested to address the latter
      and to enhance affective growth and learning.

PMID- 7510802
TI  - The role of the music therapist on the hospice/palliative care team.
AB  - Music therapists make significant contributions to the multidisciplinary hospice
      team in its efforts to provide holistic palliative care to terminally ill
      patients and family members and to promote quality of life. The role of a hospice
      music therapist is described, including providing direct patient music therapy
      service, training the hospice team in music therapy, developing and maintaining a
      music therapy resource centre, and offering bereavement services. A review of
      patient charts provides information about patient age, sex, diagnosis, and source
      and reasons for referral.

PMID- 7510804
TI  - Music and emotion in palliative care.
AB  - Music and emotion may share certain essential characteristics allowing the depth
      and breadth of music to resonate with that of emotional experience. It is perhaps
      this resonance which facilitates the experience, expression and working-through
      of feelings in music therapy work with the the terminally ill. The author
      explores five characteristics common to both music and emotion using clinical
      examples to illustrate how these might be at play in music therapy work in the
      palliative care setting.

PMID- 7510801
TI  - Palliative care in Mexico: coeliac plexus block for incidental visceral pain.

PMID- 7510805
TI  - The problematic nature of education in palliative care.
AB  - As the need for palliative care increases, palliative care is emerging as a field
      of medical care in its own right. At the same time there are many aspects of
      palliative care that are problematic, particularly in palliative care education.
      The aspects reviewed here include: (a) the lack of a long tradition and adequate
      conceptualization of palliative care; (b) the significance of psychological,
      emotional, and spiritual aspects; (c) the importance of but inadequate
      understanding of symptom control; (d) the fact that palliative care is not
      curative in the accepted sense; (e) its multiprofessional nature; (f) the range
      of different settings of palliative care; and (g) the fact that palliative
      caregivers have to perform their duties in situations where the emotional and
      psychological demands on them may be immense. A number of general issues relevant
      to palliative care education are also reviewed.

PMID- 7510806
TI  - Communicating with brain-impaired palliative care patients through music therapy.
AB  - Language is mainly a function of the left hemisphere of the brain; music is
      mainly a function of the right hemisphere. Using language and music together
      therapeutically with brain-impaired patients offers a greater chance of
      activating intact neurological pathways than using language alone. Music therapy
      also offers an alternate and creative way of communicating with these patients.

PMID- 7510807
TI  - Studies with monoclonal antibodies to the V3 region of HIV-1 gp120 reveal
      limitations to the utility of solid-phase peptide binding assays.
AB  - Using human monoclonal antibodies (HuMAbs) r(1)-447 (L-736,523) and 19b to the V3
      region of HIV-1 gp120, we have explored epitope presentation on V3-peptides and
      on the corresponding gp120 proteins. HuMAb r(1)-447 binds strongly to the MN and
      SF-2 peptides and gp120 proteins. In contrast, while this HuMAb binds equally
      avidly to both the HxB2 and the BRU/BH10 peptides, it binds but weakly to the
      HxB2 V3 loop on gp120 and fails to bind at all to BH10 gp120. Thus, the solid
      phase peptide binding assay can falsely predict reactivity of an MAb with a gp120
      protein. Conversely, HuMAb 19b fails to bind to a peptide from the V3 loop of HIV
      1 AD-6 in solid-phase assays, but binds to the same peptide in solution and also
      to AD-6 gp120. Thus, the solid-phase peptide binding assay can fail to predict
      reactivity of an MAb with a gp120 protein. Furthermore, serum antibodies from
      individual AD-6 do not react well with the AD-6 V3-peptide in a solid-phase
      assay, but react strongly with the corresponding MN V3-peptide. On the basis of
      peptide binding assays, we had assumed that the AD-6 virus was "MN-like" with a
      prototypic North American/European subtype B GPGR motif at the crown of the V3
      loop. However, direct sequencing demonstrates that the AD-6 V3 loop contains a
      variant GPGK motif. This highlights a limitation of V3-peptide-based assays for
      serotyping viruses.

PMID- 7510809
TI  - Federal agency releases guidelines for pain treatment.

PMID- 7510808
TI  - A cost analysis of approved antiretroviral strategies in persons with advanced
      human immunodeficiency virus disease and zidovudine intolerance.
AB  - Treatment with zidovudine has been standard therapy for patients with advanced
      HIV infection, but intolerance is common. Previously, management of intolerance
      has consisted of symptomatic therapy, dose interruption/discontinuation, and,
      when appropriate, transfusion. The availability of new antiretroviral agents such
      as didanosine as well as adjunctive recombinant hematopoietic growth factors
      makes additional strategies possible for the zidovudine-intolerant patient.
      Because all of these agents are costly, we evaluated the cost implications of
      these various strategies for the management of zidovudine-intolerant individuals
      within a population of persons with advanced HIV disease. We performed a decision
      analysis using iterative algorithmic models of 1 year of antiretroviral care
      under various strategies. The real costs providing antiretroviral therapy were
      estimated by deflating medical center charges by specific Medi-Cal (Medicaid)
      charge-to-payment ratios. Clinical data were extracted from the medical
      literature, product package inserts, investigator updates, and personal
      communications. Sensitivity analysis was used to test the effect of error in the
      estimation of parameters. The models predict that a strategy of dose interruption
      and transfusion for zidovudine intolerance will provide an average of 46 weeks of
      therapy per year to the average patient at a cost of $5,555/year of therapy
      provided (1991 U.S. dollars). The models predict that a strategy of adding
      hematopoietic growth factors to the regimen of appropriate patients would
      increase the average amount of therapy provided to the average patient by 3 weeks
      (6%) and the costs attributable to therapy by 77% to $9,805/year of therapy
      provided.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510810
TI  - Choroidal infiltrates as the initial manifestation of lymphoma in rheumatoid
      arthritis after treatment with low-dose methotrexate.
AB  - OBJECTIVE: To report the third known and documented occurrence of malignant
      disease as a complication of immunosuppression associated with low-dose
      methotrexate therapy for rheumatoid arthritis. MATERIAL AND METHODS: We present a
      case report of a 64-year-old woman with rheumatoid arthritis who had received low
      dose methotrexate therapy for 16 months in whom blurred vision occurred. An
      ophthalmologic examination was performed, and prednisone was administered.
      Subsequently, she complained of sore throat, weakness, and fever. An axillary
      lymph node biopsy and immunologic studies were done. RESULTS: Funduscopic
      examination revealed severe bilateral choroidal thickening. Findings on the
      biopsy disclosed a large cell, B-cell phenotype non-Hodgkin's lymphoma.
      Immunologic studies performed on frozen and paraffin-embedded tissue samples
      showed that the neoplastic cells were positive for CD20 and CD22 and without
      definite immunoglobulin light chain expression. CONCLUSION: Although the
      occurrence of lymphoma may be associated with autoimmune diseases, low-dose
      methotrexate therapy has also been implicated. Because of the increasing use of
      low-dose methotrexate therapy for classic and juvenile rheumatoid arthritis, an
      increased risk of lymphoproliferative disease is possible.

PMID- 7510812
TI  - Serum glycoprotein hormones and their free alpha-subunit in a healthy elderly
      population selected according to the SENIEUR protocol. Analyses with
      ultrasensitive time resolved fluoroimmunoassays.
AB  - The SENIEUR protocol was elaborated by a working party of European Community's
      Concerted Action Programme on Aging (EURAGE) to define strict admission criteria
      for 'healthy' elderly subjects and young controls for immunogerontological
      studies. This protocol, which is based on case history, laboratory values and
      drug consumption, intends to limit the influence of underlying disease and/or
      medication in order to allow analyses of the aging process per se. In a group of
      38 male and 37 female individuals we determined the impact of age and
      classification according to the SENIEUR protocol on luteinizing hormone (LH),
      follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG) and free
      glycoprotein hormone alpha-subunit serum values. Analyses were performed by a set
      of ultrasensitive time-resolved immunofluorometric assays (IFMA) using our own
      panel of monoclonal antibodies (MCA). HLH and hFSH, but also hCG and free alpha
      serum levels increased highly significantly with age in the female population (P
      < 0.001). In males hFSH, hLH hCG and the free alpha-subunit increased with age.
      However, only the rise of hFSH and of Free alpha was statistically significant (P
      < 0.01). The influence of the SENIEUR status on the respective hormone serum
      levels was determined using two factor analysis of variance, which revealed no
      statistically significant difference (P > 0.01) between SENIEUR and NON-SENIEUR
      individuals for all four analytes in both sexes. We conclude that the age related
      increase of hLH, hFSH, hCG and free alpha is an intrinsic age-dependent phenomen
      and is not modified by or due to underlying disease or medication as demonstrated
      by analyses of SENIEUR individuals. Since SENIEUR and NON-SENIEUR individuals had
      comparable hormone values, a randomly chosen, 'apparently healthy' population
      seems to be sufficient for physiological studies on serum GPH levels. Lastly,
      these age related hormonal changes in an extremely well defined healthy
      population underline the need for age adjusted 'normal' hormone values as
      elaborated in this communication.

PMID- 7510811
TI  - Age associated changes in mitogen induced proliferation and cytokine production
      by lymphocytes of the long-lived brown Norway rat.
AB  - The long-lived, inbred Brown Norway (BN) rat demonstrates an age associated
      decrease in lymphoproliferation in response to ConA; however, these declines only
      become apparent after the age of median survival, 31 months. Significant declines
      in IL-2 production after ConA stimulation also occur after median survival. In
      contrast, production of IFN after ConA stimulation increases with age in BN rats.
      This increase in IFN production begins about 12 months of age and plateaus at
      about median lifespan. The imbalance in IL-2 and IFN production may reflect a
      dysregulation that results in a decreased proliferative response of lymphocytes
      with increasing age.

PMID- 7510813
TI  - Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation.
AB  - Haemopoietic growth factors are accepted as accelerating haemopoietic recovery
      after bone-marrow grafting, yet no large randomised trials have been published
      that convincingly show benefit. Lenograstim (glycosylated recombinant human
      granulocyte colony-stimulating factor) was given to 315 patients after bone
      marrow transplantation in a prospective randomised placebo-controlled multicentre
      trial. 1 day after bone-marrow infusion, 163 patients received lenograstim 5
      micrograms/kg per day by 30-min infusion, and 152 patients received placebo daily
      for 28 days or until neutrophil recovery. 137 patients had lymphoma, 35 myeloma,
      85 acute lymphoblastic leukaemia, and 58 a solid tumour. Patients were stratified
      by age and by type of bone-marrow transplantation (BMT). Neutrophil recovery to
      above 10(9)/L for 3 consecutive days was seen earlier in lenograstim-treated
      patients (16 vs 27 days, p < 0.001). Time to neutrophil recovery above 0.5 x
      10(9)/L was reduced (14 vs 20 days, p < 0.001). The difference was significant
      both in autograft (20 vs 14 days, p < 0.001) and allograft (20 vs 14 days, p <
      0.01) patients, in children (20 vs 13 days, p < 0.001), and adults. Lenograstim
      treated patients had fewer days of infection, and of antibiotic administration,
      and also spent less time in hospital. However, clinical and microbiological
      sepsis was similar in both groups. There was no significant toxicity ascribed to
      lenograstim. Survival was the same at days 100 and 365. In patients undergoing
      autologous or allogeneic BMT for neoplastic disease, lenograstim significantly
      reduced duration of neutropenia and led to earlier hospital discharge.

PMID- 7510814
TI  - Histological grade of cancers detected via prostate-specific antigen screening.

PMID- 7510815
TI  - Prophylaxis and reversal of ifosfamide encephalopathy with methylene-blue.
AB  - The antineoplastic ifosfamide produces dose-dependent signs of neurotoxicity.
      After ifosfamide overdose in a patient, we found excessive urinary excretion of
      glutaric acid and sarcosine, which is compatible with glutaric aciduria type II,
      a defect in mitochondrial fatty acid oxidation that results from defective
      electron transfer to flavoproteins. We therefore used the electron-accepting drug
      methylene-blue as an antidote for ifosfamide encephalopathy. In one patient,
      ifosfamide neurotoxicity was rapidly reversed by methylene-blue 50 mg
      intravenously. In another patient with previous episodes of ifosfamide
      encephalopathy, methylene-blue was administered orally prophylactically. No
      symptoms of neurotoxicity were noted.

PMID- 7510818
TI  - [Audio-visual communication in the history of psychiatry].
AB  - The authors analyse the evolution of visual communication in the history of
      psychiatry. From the 18th century oil paintings to the first dagherrotic prints
      until the cinematography and the modern audiovisual systems they observed an
      increasing diffusion of the new communication techniques in psychiatry, and
      described the use of the different techniques in psychiatric practice. The
      article ends with a brief review of the current applications of the audiovisual
      in therapy, training, teaching, and research.

PMID- 7510816
TI  - Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis.
AB  - X-chromosome-inactivation assays can be used to assess clonality. We used such an
      assay at the human androgen-receptor gene locus in three female patients with
      histologically proven Langerhans cell histiocytosis. All patients were
      heterozygous for this locus. Cells bearing the Langerhans cell phenotype were
      purified from involved tissue after fluorescence-activated cell sorting with
      monoclonal antibodies against the CD1a complex. After HhaI digestion of DNA,
      these CD1a positive cells demonstrated a non-random X-chromosome-inactivation
      pattern, whereas CD1a negative cells in the same tissue showed a random pattern.
      Our data suggest that Langerhans cell histiocytosis represents a clonal
      proliferation of cells bearing the Langerhans cell phenotype.

PMID- 7510819
TI  - Fructose 3-phosphate and 5-phosphoribosyl-1-pyrophosphate formation in perfused
      human erythrocytes: 31P NMR studies.
AB  - 31P NMR was used to study the formation of fructose 3-phosphate (F3P) and 5
      phosphoribosyl-1-pyrophosphate (PRPP) in perfused human erythrocytes, in the
      presence of 10 different combinations and concentrations of glucose, inosine,
      pyruvate, fructose, and inorganic phosphate (Pi). (1) The cells were immobilized
      in alginate-coated agarose threads and perfused with a medium containing
      fructose, and the level of F3P increased continuously over more than 10 h. The
      net rate of F3P formation was independent of the concentration of 2,3
      bisphosphoglycerate (2,3-DPG) present in the cells. (2) PRPP was formed in high
      concentrations, relative to normal, in immobilized cells when they were perfused
      with a medium containing Pi at a low pH (6.6). (3) The 2,3-DPG level decreased
      simultaneously when the sample was perfused with a medium containing fructose,
      but without inosine or pyruvate. The measured intracellular pH and free Mg2+
      concentration were constant in these experiments. (4) The experiments confirmed
      the presence of fructose-3-phosphokinase (E.C. 2.7.1.-) and ribose-phosphate
      pyrophosphokinase (E.C. 2.7.6.1) activity in the human erythrocytes and that the
      biosynthetic pathways are active in immobilized cells at 37 degrees C. (5) The
      rates of accumulation of 2,3-DPG and phosphomonoesters (PME) appeared to be
      strongly correlated.

PMID- 7510817
TI  - Filgrastim combined with tretinoin in acute promyelocytic leukaemia.

PMID- 7510822
TI  - Sister-chromatid exchange (SCE) among individuals chronically exposed to arsenic
      in drinking water.
AB  - A study was carried out on human subjects of various ages and backgrounds who had
      been drinking water containing more than 0.13 mg/l (0.13 ppm) arsenic for a
      period of at least 20 years. The main aim was not only to correlate the frequency
      of sister-chromatid exchanges in the lymphocytes with the amount of arsenic in
      water and urine but also to correlate the frequency of SCE with sex and age. In
      addition, family background regarding skin alterations or other arsenic-related
      symptoms was explored, so that individual health conditions could be assessed.
      External factors such as exposure to other chemical or contaminating agents
      (pesticides, battery manufacturing plants, foundries) were also taken into
      consideration. The data on sister-chromatid exchanges (282 exposed and 155
      control individuals) showed that arsenic at concentrations used by our population
      (0.13 mg/l) induced a significantly elevated response. Other health effects of
      arsenic at these concentrations were found, e.g., hyperkeratosis, melanosis,
      actinic keratosis, basal cell carcinoma.

PMID- 7510821
TI  - Antigen-specific proliferative response of peritoneal exudate lymphocytes primed
      with antigen and bacterial lipopolysaccharide: the roles of Ia+ accessory cells
      and IL-2.
AB  - In vitro antigen-specific proliferation was investigated in a lymphocyte
      population that had been taken from the peritoneal exudate cells (PEC) of C3H/HeN
      mice (Iak) primed in vivo with both bacterial lipopolysaccharide (LPS) and horse
      red blood cells (HRBC) and had been purified by passage through a nylon fiber
      column (Nfc). The proliferative response of the Nfc-passed lymphocytes primed
      with HRBC and LPS [T(HRBC+LPS) cells] depended on the dose of antigen in the
      cultures, and the response was higher than that of cells prepared from mice
      primed with HRBC alone [T(HRBC) cells]. No response was seen in the cells
      prepared from the LPS-primed mice [T(LPS) cells] or normal mice [T(N) cells]. The
      response of the T(HRBC) cells was abolished by previous treatment of the cells
      with anti-Iak antibody and complement (C), whereas the response of the
      T(HRBC+LPS) cells was retained after the same treatment, indicating that the Ia-
      T(HRBC+LPS) cells can proliferate in response to antigen in spite of Ia+
      accessory cell-depletion. Supernatants from the cultures of Ia- T(HRBC+LPS) cells
      in the presence of HRBC showed abundant IL-2 activity, while those of Ia- T(HRBC)
      cells did not. The IL-2 should be produced by the L3T4 cell population in
      T(HRBC+LPS) cells in response to antigen, since the previous treatment of the
      cells with anti-L3T4 antibody and C abrogated the production.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7510820
TI  - Evaluation of a temporary arteriovenous shunt to establish neovascularization in
      a musculocutaneous flap: an experimental study.
AB  - On the dorsum of adult Sprague-Dawley rats, 3 x 7 cm pedicle flaps were raised
      and a temporary arteriovenous shunt (AVS) from anastomosis of the tail artery and
      vein was placed beneath. Fourteen, 21 and 28 days later, the pedicle flaps were
      converted to island flaps leaving only the AVS attachment. The degree of
      subsequent flap viability was directly related to the amount of time before flap
      conversion. At 14, 21 and 28 day intervals, there was 33.4%, 73.5% and 98% flap
      viability, respectively. Long-term AVS patency was found not to be required for
      flap survival. Normal hair growth, quantity and quality, occurred in only the 28
      day delay group. Microangiography and histologic examination revealed extensive
      neovascularization from both the AVS artery and vein extending into the muscle,
      subcutaneous tissue and skin layers of each island flap. In summary,
      neovascularization of a large random pattern musculocutaneous island flap is
      possible using a temporary arteriovenous shunt. Flap survival is directly related
      to the length of time between AVS placement and cutaneous pedicle division,
      although long-term AVS patency is not required for continued flap viability. Hair
      growth may directly reflect the degree of underlying neovascular maturation. This
      AVS neovascularization technique could be applied to create new donor sites for
      free tissue transfer.

PMID- 7510823
TI  - The toxic effects of cadmium on cell division and chromosomal morphology of
      Hordeum vulgare.
AB  - The effects of cadmium at different concentrations (0.5-20 ppm) on root growth,
      cell division and chromosomal morphology of Hordeum vulgare were studied. The
      rate of root growth and mitotic index decreased progressively with increasing
      cadmium concentration and treatment duration. Different concentrations of cadmium
      could cause mitotic irregularities comprising c-mitoses, anaphase bridges,
      breaks, stickiness, lagging and vagrant chromosomes and micronuclei. The
      intensity of the toxic effects is basically dependent on the cadmium
      concentration and duration of treatment.

PMID- 7510824
TI  - Micronucleus formation in fetal maternal rat erythroblasts after norfloxacin
      transplacental administration.
AB  - Single oral doses of norfloxacin (4, 2, 1, 0.5 mmole/kg) administered to pregnant
      rats significantly increase the frequency of micronucleated polychromatic
      erythrocytes both in fetal liver and in maternal bone marrow. Therefore
      norfloxacin in this work has been found to be a genotoxic agent.

PMID- 7510825
TI  - Rapid inactivation of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX),
      a potent mutagen in chlorinated drinking water, by sulfhydryl compounds.
AB  - The mutagenic activity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone
      (MX), which is formed during chlorination of drinking water, was effectively
      inhibited by sulfhydryl compounds such as cysteine, cysteamine, glutathione,
      dithiothreitol and 2-mercaptoethanol. Preincubation of 0.5 micrograms MX with 15
      micrograms cysteine (molar ratio 1:37) in a phosphate buffer (pH 6.0-8.0) at 37
      degrees C for 15 min prior to exposure of bacterial cells depleted the mutagenic
      activity of MX. Together with the result showing a change in the UV spectra, it
      is suggested that sulfhydryl compounds inactivate MX by direct chemical
      interaction before MX induces DNA damage. On the other hand, a variety of
      antioxidants other than the sulfhydryl compounds showed no inhibitory effects.
      Investigation using structural analogs of cysteine revealed that the thiol moiety
      was indispensable for antimutagenic activity and the amino moiety appeared to
      enhance the MX-inactivating reaction of the SH group.

PMID- 7510828
TI  - Budapest Registry of Self-poisoned Patients.
AB  - The majority of persons attempting suicide are young (peak in the 17-19 age
      group), female (68%), otherwise healthy, and use chemicals for this purpose (self
      poisoning); 98% of these persons survive. Thus, survivors of self-poisoning
      present a unique model for the study of somatic and germinal mutagenic effects of
      large doses of chemicals in human beings. This recognition prompted the
      establishment of the Budapest Registry of Self-poisoned Patients in 1990. The
      recorded 11,847 cases used 20,324 drugs in 1990-1992. Benzodiazepines were the
      most popular drugs for self-poisoning. International collaboration by the use of
      molecular epidemiological methods seems to be promising in the self-poisoning
      model.

PMID- 7510826
TI  - Replicate flasks are not necessary for in vitro chromosome-aberration assays in
      CHO cells.
AB  - Some recommended protocols for in vitro chromosome-aberration assays call for two
      flasks per dose group. Use of replicate flasks allows for possible variation in
      percent aberrant cells (ABR) between flasks. We studied the magnitude of
      variation between replicate flasks of Chinese hamster ovary (CHO) cells using
      data from 211 assays from three laboratories, in order to assess the effect on
      assay sensitivity. Based on all 403 pairs of replicate "control" flasks, there
      was almost no excess variability between flasks. The standard deviation (SD) was
      only 4% larger than the value expected purely from sampling cells (P > 0.05).
      Data from all 366 pairs of replicate "treated" flasks showed that between-flask
      variation increased with the average percent aberrant cells (P < 0.001). The SD
      for 60 pairs of flasks with 3.0-7.5% ABR cells was 32% larger than the expected
      value. However, computer simulations based on these data showed use of replicate
      flasks has little effect on assay false-positive or true-positive rates. All
      assays with replicate treated flasks and at least three dose groups including
      control were re-analyzed as "single-flask" experiments. A "single-flask"
      experiment was defined by taking both control flasks but only one treated flask
      per dose. For each assay, all possible single-flask experiments were re-analyzed
      and the percent with positive results recorded. For most assays, conclusions were
      the same regardless of which treated flasks were selected, in spite of the fact
      that these single-flask experiments had only half as many cells scored per active
      dose group. For a very few assays with marginal results, the conclusion could
      change depending on which set of flasks was chosen, but these were such
      borderline results that a repeat assay was required in any case. Repeating the
      assay is a better way to resolve marginal results than examining replicate
      flasks. From our re-examination of the experimental data and from the computer
      simulation, we conclude that, while flask-to-flask variability exists, it has no
      practical effect on the test outcome, so that use of replicate flasks is not
      necessary for this assay.

PMID- 7510830
TI  - Software for the analysis of mutations at the human hprt gene.
AB  - Mutations at the human hypoxanthine-guanine phosphoribosyl transferase gene
      (hprt) are currently of great interest because mutations at this locus are being
      used as a biomonitor of human mutagenic exposure. Not only can somatic hprt
      mutants arising in vivo in humans be recovered and sequenced, but there is also a
      considerable body of information about the in vitro mutational spectra of
      different carcinogens at this locus. Previously, we reported the creation of a
      computerized database containing DNA-sequence information on human hprt mutants
      (Cariello et al. (1992) Environ. Mol. Mutagen., 20, 81-83). In the present
      manuscript, software for the analysis of mutations in the hprt database is
      described. Numerous routines have been developed for the analysis of single-base
      substitutions, including programs to (i) determine if two mutational spectra are
      different, (ii) display the number of mutations and mutable sites in each exon,
      (iii) determine if mutations show a DNA-strand bias, (iv) determine the frequency
      of transitions and transversions, (v) display the number and kind of mutations
      observed at each base in the coding region, (vi) perform nearest-neighbor
      analysis and (vii) display mutable amino acids in the hprt protein. The software
      runs only on IBM-compatible machines with MS-DOS. The software and hprt database
      is freely available via the INTERNET using remote file-transfer protocol. These
      programs simplify the analysis of the rapidly increasing information about hprt
      mutation. The programs permit the facile comparison between in vitro and in vivo
      data, as well as the identification of mutational patterns that may be of
      importance to experimenters using hprt as a biomonitor and and of importance to
      researchers studying mechanisms of mutation.

PMID- 7510831
TI  - No significant increase in sister-chromatid exchanges in cultured blood
      lymphocytes from workers in a large oil refinery.
AB  - In order to assess the potential genotoxic effects of occupational exposure to
      petrochemicals, the incidence of sister-chromatid exchanges (SCE) in cultured
      lymphocytes was studied. Blood samples were taken from 233 individuals (184
      exposed and 49 worksite controls) in an oil refinery and from 47 community
      control persons. The data showed a non-significant elevation of SCE frequency in
      occupationally exposed workers when compared to non-exposed individuals. The mean
      SCE frequency per cell ranged from 7.55 +/- 0.55 in blood of lube oil blending
      and canning (LOBC) workers to 9.13 +/- 0.71 in catalytic cracking and water
      treatment (CCWT) workers. The control values were 6.2 +/- 0.67 and 7.21 +/- 0.45
      in the community and worksite individuals, respectively. Furthermore, the SCE
      frequencies were influenced neither by age nor by smoking.

PMID- 7510829
TI  - Induction of in vivo DNA adducts by 4 industrial by-products in the rat-lung-cell
      system.
AB  - Benz[a]anthracene (BA), dibenz[a,h]anthracene (DBA), dibenzo[a,i]pyrene (DBP),
      and dibenz[a,h]acridine (DBAC) are by-products found in many industrial wastes
      and emissions. Workers in the related occupational settings are potentially
      exposed to these substances through inhalation. In the present study, induction
      of DNA adducts in vivo by these chemicals was investigated using 32P-postlabeling
      analysis in the rat-lung-cell system. The potency of DNA-adduct inducing activity
      was also compared to that of two cytogenetic endpoints i.e., sister-chromatid
      exchange (SCE) and micronucleus formation. Via intratracheal instillation, male
      CD rats (6/group) were dosed 3 times with BA, DBA, DBP or DBAC in a 24-h
      interval. Lung cells were enzymatically separated and used to determine the
      frequency of DNA adducts, SCE and micronuclei. Results show that all 4 test
      compounds induced DNA adducts, SCEs, and micronuclei in the rat-lung cell in vivo
      and that the postlabeling DNA adduct assay detected genotoxic activity at lower
      dose levels than the two cytogenetic assays. These findings suggest that BA, DBA,
      DBP or DBAC are rat pulmonary genotoxicants and the DNA-adduct assay is more
      sensitive than SCE or micronucleus assays for detecting the pulmonary
      genotoxicity of these industrial PAHs in the in vivo rat-lung-cell system.

PMID- 7510832
TI  - Latin American Workshop on Genetic Toxicology. I. Drosophila melanogaster.

PMID- 7510827
TI  - Clastogenicity of red pepper (Capsicum frutescens L.) extracts.
AB  - Extracts from the fruits of Capsicum frutescens L. were tested for their
      clastogenicity using the mouse-bone-marrow micronucleus (mouse-MN) assay. Results
      of the mouse-MN, an in vivo method, indicated that the isolate CF-1 is
      clastogenic at the maximum tolerated dose of 1.22 mg/kg mouse. Statistical
      analysis using the Wilcoxon two-sample test showed that the null hypothesis, mu
      tetracycline = muCF-1, is acceptable at 0.05 and 0.01 degrees of significance.
      Hence, the clastogenicity of CF-1 is statistically similar to that of
      tetracycline, a known clastogen, at the 5% and 1% levels of significance.

PMID- 7510833
TI  - Deletion and duplication sequences induced in CHO cells by teniposide (VM-26), a
      topoisomerase II targeting drug, can be explained by the processing of DNA nicks
      produced by the drug-topoisomerase interaction.
AB  - Frameshift mutations induced by acridines in bacteriophage T4 have been shown to
      be due to the ability of these mutagens to cause DNA cleavage by the type II
      topoisomerase of T4 and the subsequent processing of the 3' ends at DNA nicks by
      DNA polymerase or its associated 3' exonuclease followed by ligation of the
      processed end to the original 5' end. An analysis of the ability of nick
      processing models is presented here to test the ability of nick processing to
      account for the DNA sequences of duplications and deletions induced in the aprt
      gene of CHO cells by teniposide (VM-26) [Han et al. (1993) J. Mol. Biol., 229,
      52]. Although teniposide is not an acridine, it induces topoisomerase II-mediated
      DNA cutting in aprt sequences in vitro and mutagenesis in vivo. Although the
      previous study noted a correlation between mutation sites and nearby DNA
      discontinuities induced by the enzyme in vitro, neither the nick-processing model
      responsible for T4 mutations, nor double-strand break models alone were able to
      account for most of the mutant sequences. Thus, no single model explained the
      correlation between teniposide-induced DNA cleavage and mutagenic specificity.
      This report describes an expanded analysis of the ways that nick-processing
      models might be related to mutagenesis and demonstrates that a modified nick
      processing model provides a biochemical rationale for the mutant specificities.
      The successful nick-processing model proposes that either 3' ends at nicks are
      elongated by DNA polymerase and/or that 5' ends of nicks are subject to nuclease
      activity; 3'-nuclease activity is not implicated. The mutagenesis model for nick
      processing of teniposide-induced nicks in CHO cells when compared to the
      mechanism of nick-processing in bacteriophage T4 at acridine-induced nicks
      provides a framework for considering whether the differences may be due to cell
      specific modes of DNA processing and/or due to the precise characteristics of
      topoisomerase-DNA intermediates created by teniposide or acridine that lead to
      mutagenesis.

PMID- 7510834
TI  - Mutagenic risk in psoriatic patients before and after 8-methoxypsoralen and long
      wave ultraviolet radiation.
AB  - Sister-chromatid exchange (SCE) analysis was carried out in different age groups
      prior to and after therapy with 8-Methoxypsoralen (8-MOP) followed by exposure of
      the patient to long-wave UV-A (PUVA) and compared to control. The SCE frequencies
      were increased significantly in PUVA-treated patients as compared to their pre
      treatment SCE levels and to controls. A significant increase in SCEs was found in
      smoking PUVA-treated patients as compared to non-smoking PUVA-treated patients.
      This study indicates a detectable chromosome-damaging effect of PUVA therapy on
      its human users.

PMID- 7510835
TI  - An in situ protocol for measuring the expression of chemically-induced mutations
      in mammalian cells.
AB  - The generation of expression curves and the evaluation of mutagenic responses of
      mammalian cells using standard mutagenesis assays can be inaccurate because
      mutant and wild-type cells are usually mixed during the expression phase. If some
      mutant progenitors or mutants grow more slowly than the wild-type cells during
      the expression period, there will be a decrease in the mutant to wild-type ratio
      with time and the mutant fraction will not accurately represent the number of
      mutational events that occurred. The mutant fraction may also inaccurately assess
      the number of mutations if these mutations are expressed over a number of
      generations during the time before selection. We previously showed that recovery
      of L5178Y mouse cell mutants is not complete when mutations are allowed to
      express in suspension because slowly growing mutants and/or mutant progenitors
      are diluted out during this time (Rudd et al., 1990). In order to more accurately
      quantitate the mutagenic response of the cells, we developed an in situ procedure
      which segregates and immobilizes cells during expression. Because of this
      immobilization, slowly growing mutant progenitors and mutants expressed at
      different times will have an equal probability of being scored as mutants. Thus,
      one mutation leads to one mutant colony and the measurement of the mutagenic
      response of the cells to the chemical accurately reflects the mutational events
      that occurred. We plated L5178Y tk+/- mouse cells in semisolid medium immediately
      after treatment. As the cells grew and formed microcolonies, the selective agent
      TFT was added as an overlay at specified times, permitting only TFTr cells to
      survive. In this procedure, each mutation was captured as an individual colony;
      consequently, the measured mutation fraction accurately reflected the mutational
      events that occurred at the selected locus. In addition, the induced mutant
      colonies arising in the agar are the result of independent mutational events. We
      previously described the in situ protocol for L5178Y cells and showed that the
      spontaneous mutation rate measured was 50-fold greater than when the cells
      expressed the phenotype in suspension (Rudd et al., 1990). From this we concluded
      that the slow growth phenotype was expressed before TFT resistance. In the
      present paper, we evaluate the effect of chemical treatment on the mutation
      fraction as a function of the time to TFT addition. Using the in situ protocol,
      we generated expression curves for three nucleotide analogs, 5-azacytidine, TFT
      and AraC. The numbers of TFTr colonies produced at various times after treatment
      indicated that chemically-treated cultures had higher mutation fractions than the
      solvent controls.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7510836
TI  - Isolation and prevalidation of an Escherichia coli tester strain for the use in
      mechanistic and metabolic studies of genotoxins.
AB  - We have isolated an Escherichia coli tester strain for the use in mechanistic and
      metabolic studies of genotoxins. We started with one of the more used and better
      characterized E. coli K-12 laboratory strains, AB1157. We isolated a
      lipopolysaccharide defective mutant of strain AB1886 which is an excision repair
      deficient derivative of AB1157 and introduced a newly constructed plasmid pKR11,
      encoding mucAB, resulting in strain MR2101/pKR11. A genotoxicity assay was
      designed, monitoring the reversion to arginine prototrophy and a preliminary
      validation was carried out against Ames tester strain TA100 with a set of
      diagnostic compounds. The results seem to indicate that strain MR2101/pKR11 is an
      adequate tester strain which can be a useful tool in mechanistic studies.
      Moreover, this strain can serve as mother strain to isolate improved and more
      specialized tester strains.

PMID- 7510837
TI  - Genotoxicity evaluation of pyrazinamide in mice.
AB  - Pyrazinamide, an antituberculosis drug, was investigated for genotoxicity in
      mice, an in vivo rodent system. Three doses (125, 250 and 500 mg/kg bw
      corresponding to 5, 10 and 20 times the therapeutic dose respectively) were
      tested. The mitotic index and the frequency of chromosomal aberrations were
      analysed at three sample times (3, 6 and 24 h) after a single intraperitoneal
      treatment. The frequency of sperm shape abnormalities was also examined. The
      mitotic index showed a decrease in drug-treated animals compared with that
      recorded in the control set. The cells with chromosomal aberrations ranged from
      4% to 8%. The maximum frequency of aberrations was found at the 3-h sample time.
      The frequency of sperm shape abnormalities showed a dose-related increase. These
      observations suggest pyrazinamide to be a weak genotoxicant at the doses tested.

PMID- 7510838
TI  - Mutagenic potential of acute exposure to organophosphorus and organochlorine
      compounds.
AB  - The cytogenetic and cytotoxic effects of the pesticides methyl parathion,
      Bayleton and Hinosan were evaluated in mammalian test systems. The frequency of
      chromosome aberrations and micronuclei in bone marrow cells and the arginase
      enzyme profile in the liver tend to show the genotoxicity of organophosphorus and
      organochlorine pesticides in a single-exposure response study. Methyl parathion
      was the most hazardous among the three, showing definite pathology in the livers
      of treated rats.

PMID- 7510842
TI  - DNA-directed aniline mustards with high selectivity for adenine or guanine bases:
      mutagenesis in a variety of Salmonella typhimurium strains differing in DNA
      repair capability.
AB  - Two closely-related aniline monomustards (1 and 2), linked to a DNA-targeting
      acridine chromophore by a linker chain of different length, show high selectivity
      for alkylation of polymer DNA. The shorter-chain derivative (2) alkylates mainly
      at guanine N7 sites, while the longer-chain analogue (1) reacts almost
      exclusively at adenine N1. The biological effects of these compounds have been
      studied in standard Ames Salmonella typhimurium strains in order to determine the
      mutagenic consequences of such well-defined DNA lesions, and the effect of DNA
      repair systems on them. Both compounds caused detectable mutations in strains
      TA1537, TA98 or TA100 and some related strains. Mutation rates were greatly
      enhanced in strains carrying either a uvrB deletion or the plasmid pKM101.
      Frameshift mutagenesis by both compounds was completely eliminated by recA
      deletion, in both the presence or absence of the plasmid. The adenine-selective
      compound (1) appeared more sensitive to the DNA-repair defects than the guanine
      selective derivative (2). Additionally, only the adenine-selective compound (1)
      caused statistically significant levels of detectable mutation in the repair
      proficient strains TA102, TA4001 or TA4006. The bacterial mutagenesis evidence
      suggests that a bulky, major groove-residing adenine lesion may be more readily
      recognised by DNA-repair systems, and more likely to lead to a wider range of
      mutagenic events, than a similar guanine lesion.

PMID- 7510841
TI  - The genetic activity of 6-N-hydroxylaminopurine in Aspergillus nidulans.
AB  - The activity of a base analog (6-N-hydroxylaminopurine, HAP) has been tested on
      Aspergillus nidulans. In germinating haploid conidia HAP is a strong mutagen,
      while it does not have any activity in resting conidia. Moreover, HAP does not
      increase the frequency of recombination in germinating conidia. The mutagenic
      activity of this base analog has also been tested in diploid conidia of A.
      nidulans; in fact, it has been shown (Pavlov et al., 1991) that the HAP-induced
      frequency of heteroallelic recessive mutations in diploid cells of the yeast S.
      cerevisiae is higher than expected. In A. nidulans, we did not observe any
      increase in the frequency of recessive homozygous fpaA/fpaA (p
      fluorophenylalanine-resistant) mutants over the expected one, which has been
      calculated on the basis of the observed mutation frequency in the haploid strain.

PMID- 7510839
TI  - Genotoxic activity of azidothymidine (AZT) in in vitro systems.
AB  - The genotoxic activity of azidothymidine (AZT) was evaluated in vitro, measuring
      cytogenetic parameters in two cell systems. In human lymphocytes AZT induced a
      statistically significant increase in chromosome breakage at 100 micrograms/ml
      and in micronucleated cells at the highest dose assayed (500 micrograms/ml).
      Sister-chromatid exchanges (SCE) showed a two-fold increase over control values
      at 50 micrograms/ml. Lymphocyte cycle kinetics showed an important delay at 500
      micrograms/ml. In Chinese hamster ovary (CHO) cells, AZT produced a significant
      increase in chromosome aberrations and SCE at 1000 and 500 micrograms/ml,
      respectively. At 2500 micrograms/ml the drug produced a delay in cell cycle
      progression. These results suggest that AZT is a DNA-damaging agent in both cell
      systems assayed. Moreover, human lymphocytes seem to be more sensitive to AZT
      than CHO cells.

PMID- 7510840
TI  - Genotoxicity assessment of the antifungal antibiotic aureofungin in Salmonella
      typhimurium and Swiss albino mice.
AB  - The widely used agricultural antifungal agent aureofungin (ARF) was subjected to
      genotoxicity assessment using the Ames Salmonella assay as well as the in vivo
      micronucleus test and dominant lethal test in Swiss mice. In the Ames Salmonella
      spot test, ARF slightly elevated the number of histidine revertants after
      metabolic activation over a wide dose range (1-1000 micrograms/plate) in TA102
      but not in TA97a, TA98 or TA100. In the preincubation plate incorporation assay
      with TA102, ARF increased the number of revertants in a dose-dependent manner
      only after metabolic activation. ARF failed to significantly elevate the
      frequency of micronucleated polychromatic erythrocytes (PE) in the bone marrow of
      Swiss mice. It elevated the frequency of dominant lethal mutations in the 7th and
      8th weeks at 30 mg/kg body weight, a concentration much higher than the actual
      concentration used in the field. We conclude that ARF is non-mutagenic in somatic
      cells in vivo at doses used in the present study, probably mutagenic in stem-cell
      spermatogonia and may be classified as an equivocal promutagen, possibly acting
      as a cross-linker.

PMID- 7510843
TI  - Genotoxicity of vanadium pentoxide in Chinese hamster V79 cells.
AB  - Workers in many mining and manufacturing industries are potentially exposed to
      vanadium. Inhalation of dust containing vanadium pentoxide (V2O5), a pentavalent
      compound of vanadium, has been reported to cause lung diseases. Information
      related to the genotoxicity and potential carcinogenicity of V2O5, however, is
      still limited. In this study, the effect of V2O5 on mitosis, sister-chromatid
      exchange (SCE), micronucleus formation (MN), and gene mutation in Chinese hamster
      V79 cells was determined. Cells were treated with varying concentrations of V2O5
      for 24 h. The results showed that no significant increases in the frequencies of
      SCE or gene mutation occurred in V2O5-treated cultures. However, dose-related
      increases were noted for micronucleated cells in cultures exposed to this
      compound, and the number of binucleated cells in the presence of cytochalasin B
      was found to decrease with increasing V2O5 concentrations. Since the
      micronucleated cells induced by V2O5 contained kinetochore-positive micronuclei,
      their induction appears to be due to damage to the spindle apparatus. These
      results indicate that V2O5 is cytotoxic and aneuploidogenic to V79 cells.

PMID- 7510844
TI  - Evaluation of carbendazim for gene mutations in the Salmonella/Ames plate
      incorporation assay: the role of aminophenazine impurities.
AB  - Benomyl (methyl [1-[(butylamino)carbonyl]-1H-benzimidazol-2- yl]carbamate) and
      its major metabolite carbendazim (methyl 2-benzimidazolecarbamate) are major
      agricultural systemic fungicides. These compounds inhibit fungal microtubular
      function and thereby cause nondisjunction of chromosomes at cell division.
      Several investigators have proposed that these compounds can also cause gene
      mutations (base-pair substitutions). In this laboratory, no mutagenic activity
      was observed with either benomyl (analytical grade) or Benlate (samples tested up
      to 500 and 1200 micrograms/plate, respectively, the limit of cytotoxicity) in the
      Salmonella/Ames plate-incorporation test in either base-pair substitution (TA100
      and TA1535) or frameshift-sensitive (TA98 and TA1537) strains with or without S9
      metabolic activation. However, some carbendazim preparations caused mutations in
      frameshift-sensitive strains at very high concentrations (> or = 5000
      micrograms/plate) with metabolic activation. The mutagenic activity was not due
      to the major carbendazim metabolite, methyl (5-hydroxy-1H-benzimidazol-2
      yl)carbamate (5-OH MBC), since 5-OH MBC was not mutagenic with (up to 20,000
      micrograms/plate) or without (up to 16,000 micrograms/plate) activation.
      Subsequently, two highly mutagenic contaminants, 2,3-diaminophenazine (DAP) and 2
      amino-3-hydroxyphenazine (AHP) were detected in mutagenic carbendazim samples. In
      those samples, DAP and AHP contaminant levels ranged as high as 46.5 and 11.6
      ppm, respectively. No evidence of mutagenicity could be detected in preparations
      in which the DAP content was < 1.8 ppm. The mutagenic activity of these two
      contaminants was further investigated in strain TA98. Without activation, DAP and
      AHP were positive at test concentrations as low as 5 and 10 micrograms/plate,
      respectively. In the presence of S9, mutations were detected at much lower
      concentrations (beginning at 0.025 and 0.05 microgram/plate, respectively). These
      results indicate that carbendazim samples containing DAP or AHP at levels as low
      as 5 or 10 ppm, respectively, would be positive in the Salmonella/Ames test with
      activation when tested at 5000 micrograms/plate. Purified carbendazim is not
      mutagenic.

PMID- 7510845
TI  - Absence of unscheduled DNA synthesis in rat hepatocytes treated with mutagenic
      and cytotoxic chlorinated humic substances.
AB  - Chlorinated hydrophilic macromolecular humic acids (CHMA) (0.07-3.0 mg per plate)
      were mutagenic in Salmonella typhimurium strain TA100. In contrast, the
      chlorinated derivatives did not induce unscheduled DNA synthesis (nuclear
      incorporation of [3H]thymidine) in cultured rat hepatocytes even after depletion
      of intracellular glutathione with buthionine sulphoximine (0.001 mM) and at
      concentrations of CHMA up to 3.0 mg per plate eliciting cytotoxicity. Glutathione
      depletion did however potentiate cytotoxicity and hepatocyte glutathione
      concentrations were lowered by CHMA treatment indicating reactivity of CHMA in
      the cell.

PMID- 7510847
TI  - The mutagenicity of nitrite in the Salmonella/microsome test system.
AB  - The bacterial strains of Salmonella typhimurium used for detection of base-pair
      substitutions (TA1530, TA1535, TA100 and TA102) and various types of frameshift
      mutations (YG1024, DJ400 and DJ460) were exposed to nitrites in the
      Salmonella/microsome test system. In agreement with published data, nitrites
      exhibited mutagenic activity in standard strains TA1530, TA1535 and TA100. The
      TA102 strain was insensitive as were the frameshift tester strains despite their
      genetically manipulated genome increasing their sensitivity.

PMID- 7510848
TI  - Single-base deletion induced by benzo[a]pyrene diol epoxide at the adenine
      phosphoribosyltransferase locus in human fibrosarcoma cell lines.
AB  - Benzo[a]pyrene diol epoxide (BPDE), a metabolic product of benzo[a]pyrene, is one
      of the most widely distributed environmental carcinogens. In this study, we
      demonstrate that BPDE produces a dose-dependent increase in the frequency of APRT
      gene reversion in the APRT-deficient cell line, HTD114, which contains single
      nucleotide insertions at different positions in each APRT allele. The highest
      reversion frequency observed after BPDE exposure was 3.3 +/- 0.9 x 10(-5), at
      least 10(3)-fold greater than the spontaneous frequency. Reversion of either
      mutant allele was observed to be a consequence of a frame-restoring loss of a
      single nucleotide. A similar frequency of BPDE-induced reversion at APRT also was
      observed in a cell line containing only one type of the mutant alleles of HTD114,
      thus eliminating the possibility that gene conversion plays a major role in APRT
      gene reversion in HTD114 cells. Therefore, the data demonstrate that BPDE can
      function as an effective frameshift mutagen in human cells.

PMID- 7510849
TI  - Inhibition of the bacterial mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine
      by ascorbic acid and ascorbyl palmitate.
AB  - The mechanism of antimutagenic activity of ascorbic acid (AA) and its derivatives
      was studied using the Salmonella typhimurium TA100 bacterial test system. All
      substances studied inhibited N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced
      mutagenesis. Ascorbyl palmitate (AP) markedly decreased the numbers of his+
      revertants, behaving as a membrane-active antimutagen. A comparative study of the
      antioxidative activity of the investigated substances in the methyl oleate (MO)
      system has demonstrated that AA and its derivatives have pro-oxidant properties
      within the limits of the concentrations studied. The results obtained do not
      agree with the common view of the mode of action of these antimutagens, including
      both inhibition of free radical processes and MNNG reductive inactivation.

PMID- 7510846
TI  - Propane 2-nitronate is the major genotoxic form of 2-nitropropane.
AB  - The mutagenicity of 2-nitropropane in Salmonella typhimurium (strain TA100) was
      proportional to the pH (range 6.1-9.1) of the medium used for pre-incubation of
      the agent and for incubation of the agent with the Salmonella. The mutagenicity
      correlated with an enhanced rate of tautomerase to propane 2-nitronate at
      relatively high pH as measured by high performance liquid chromatography. Both
      the mutagenicity in Salmonella typhimurium (strains TA100 and TA102) and the rate
      of tautomerisation to the nitronate was lower with 2-deutero-2-nitropropane than
      with non-deuterated 2-nitropropane. Furthermore, 2-deutero-2-nitropropane was
      less potent in the induction of unscheduled DNA synthesis in rat hepatocytes over
      a 4-h period. Propane 2-nitronate therefore appears to be pivotal in the
      causation of the genetic toxicity of 2-nitropropane. The presence of hepatocytes
      enhanced nitronate production from 2-nitropropane suggesting a contribution from
      hepatic enzymes in the tautomerisation reaction.

PMID- 7510850
TI  - The comparative clastogenic activity of mainstream tobacco smoke from cigarettes
      widely consumed in Armenia.
AB  - Whole-body exposure of male albino Swiss mice to the mainstream smoke produced by
      10 types of cigarettes widely consumed in Armenia resulted in a significant
      increase (2.4-5.6-fold) of the number of micronucleated bone marrow polychromatic
      erythrocytes. The smoke produced by cigarettes manufactured in Armenia, Russia
      and Bulgaria was more clastogenic than the smoke produced by cigarettes
      manufactured in the USA. A high direct correlation was observed between the
      number of micronucleated polychromatic erythrocytes and the content of tar and
      nicotine.

PMID- 7510851
TI  - Metal-induced genotoxic adaptation in barley (Hordeum vulgare L.) to maleic
      hydrazide and methyl mercuric chloride.
AB  - Presoaked seeds of barley, Hordeum vulgare L., were exposed for 2 h to maleic
      hydrazide (MH), 5 x 10(-2) M or methyl mercuric chloride (MMCl), 10(-4) M with or
      without a prior conditioning with MH, 5 x 10(-3) M; MMCl, 10(-5) M; cadmium
      sulfate (CdSO4), 10(-4) M or zinc sulfate (ZnSO4), 10(-1) M; the interexposure
      time was 2 h. Subsequently as the seeds germinated a number of endpoints were
      measured that included mitotic index, mitotic chromosome aberrations and
      micronuclei (MNC) in embryonic shoot cells fixed at 32, 36, 40, 44, 48 and 52 h
      of recovery, and seedling height on day 7. The results demonstrated that prior
      conditioning exposure to MH or metals induced genotoxic adaptation to the
      subsequent challenge exposure to MH and MMCl. Cadmium-induced genotoxic
      adaptation against either MH or MMCl challenge exposure was, however,
      significantly prevented when the presoaked seeds were pre-exposed to buthionine
      sulfoximine, 10(-3) M for 2 h, thereby providing evidence that the underlying
      mechanism of genotoxic adaptation possibly involved phytochelatins.

PMID- 7510852
TI  - Reducing the need for amniocentesis in women 35 years of age or older with serum
      markers for screening.
AB  - BACKGROUND: As maternal age advances, the risk of fetal Down's syndrome
      increases. Pregnant women 35 years of age or older are routinely offered
      amniocentesis because of this risk. Recently, maternal serum markers have been
      reported to be useful in screening for Down's syndrome, primarily in younger
      women. We therefore investigated whether offering amniocentesis only to selected
      women 35 years of age or older who were identified by screening measurements in
      serum might prove a useful alternative to the current practice. METHODS: We
      studied 5385 women with singleton pregnancies who were 35 years of age or older
      and were undergoing routine amniocentesis. Along with information about the
      pregnancy, we obtained a serum sample for measurement of alpha-fetoprotein,
      unconjugated estriol, and human chorionic gonadotropin. Individual estimates of
      the risk of Down's syndrome in the fetus were calculated for each pregnancy
      before the karyotype was known. RESULTS: If amniocentesis had been reserved for
      the women calculated to have a risk greater than 1 in 200 of having a fetus with
      Down's syndrome, 48 of the 54 cases of Down's syndrome (89 percent) would have
      been identified, 25 percent of the unaffected pregnancies would also have been
      identified as being at high risk for Down's syndrome (false positives). Seven of
      15 fetuses (47 percent) with other trisomies, 11 of 25 (44 percent) with sex
      aneuploidy, and 1 of 9 (11 percent) with miscellaneous chromosomal abnormalities
      would also have been detected. In practice, such screening would have made 75
      percent of the amniocentesis unnecessary, along with a proportion of the
      amniocentesis-associated fetal losses. If the cutoff for the risk of Down's
      syndrome were set higher than 1 in 200, both the rate of detection and the false
      positive rate would be lower. Conversely, these rates would be higher if the
      cutoff were set lower. CONCLUSIONS: Prenatal screening of serum to generate
      individual estimates of the risk of Down's syndrome in the fetus can provide a
      basis for decision making in the cases of women 35 years of age or older, as it
      does in younger pregnant women, and is an alternative to current testing
      practices.

PMID- 7510853
TI  - High resolution of human evolutionary trees with polymorphic microsatellites.
AB  - Genetic variation at hypervariable loci is being used extensively for linkage
      analysis and individual identification, and may be useful for inter-population
      studies. Here we show that polymorphic microsatellites (primarily CA repeats)
      allow trees of human individuals to be constructed that reflect their geographic
      origin with remarkable accuracy. This is achieved by the analysis of a large
      number of loci for each individual, in spite of the small variations in allele
      frequencies existing between populations. Reliable evolutionary relationships
      could also be established in comparisons among human populations but not among
      great ape species, probably because of constraints on allele length variation.
      Among human populations, diversity of microsatellites is highest in Africa, which
      is in contrast to other nuclear markers and supports the hypothesis of an African
      origin for humans.

PMID- 7510854
TI  - Role of L-type calcium channels on yohimbine-precipitated clonidine withdrawal in
      vivo and in vitro.
AB  - This study was designed to elucidate the possible participation of L-type calcium
      channels in the expression of clonidine-withdrawal precipitated by yohimbine in
      clonidine-dependent animals. Mice implanted for 5 days with osmotic minipumps
      containing the alpha 2-adrenoceptor agonist clonidine showed symptoms of a
      withdrawal syndrome (jerks, headshakes, defecations and weight loss) when
      yohimbine, an alpha 2-adrenoceptor antagonist, was injected. Similarly, isolated
      rat ilea incubated with clonidine in vitro showed a withdrawal contracture when
      yohimbine was added to the organ bath. The effects of L-type calcium channel
      blockers (verapamil and diltiazem) and the stimulant Bay K 8644 on these two
      different types of withdrawal responses were evaluated. A dose-dependent decrease
      in yohimbine-precipitated clonidine withdrawal in vivo was observed when
      verapamil (10-40 mg/kg, s.c. and 120 micrograms/mouse, i.c.v.) or diltiazem (5-20
      mg/kg, s.c. and 160 micrograms/mouse, i.c.v.) were administered to mice dependent
      on clonidine. No effect was found after Bay K 8644 (0.5-5 mg/kg, s.c. and 1-5
      micrograms/mouse) was injected under these conditions. In vitro, both verapamil
      (0.1-5 microM) and D-cis-diltiazem (1-50 microM) concentration-dependently
      reduced the height of the yohimbine-precipitated withdrawal contracture in rat
      ileum incubated with clonidine. Furthermore, the effect of diltiazem was
      stereospecific, as D-cis-diltiazem 10 microM markedly inhibited clonidine
      withdrawal, whereas the same concentration of L-cis-diltiazem had no effect. In
      contrast, the calcium channel stimulant Bay K 8644 (0.1-1 microM) increased the
      height of the ileum withdrawal contracture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510855
TI  - Capsaicin sensitive nerves in the jejunum of Nippostrongylus brasiliensis
      sensitized rats participate in a cardiovascular depressor reflex.
AB  - Superfusion of capsaicin onto the serosal surface of jejunum of Nippostrongylus
      brasiliensis-sensitized rats induces a short-lasting (1-3 min), dose-dependent (2
      to 20 micrograms) decrease in blood pressure which ranges from -5.3 +/- 1.4% to 
      22.6 +/- 2.2%. The hypotension evoked by capsaicin was more marked in sensitized
      rats than in unsensitized animals, which responded only to the highest dose (20
      mg) of capsaicin tested. The hypotensive effects of capsaicin were not affected
      by intravenous injections of mepyramine (10 mg/kg), a histamine receptor
      antagonist, or by the cyclooxygenase inhibitor indomethacin (10 mg/kg). However,
      an intravenous injection of a platelet-activating factor (PAF) antagonist, BN
      52021 (20 mg/kg), or an intraperitoneal injection of guanethidine (8 mg/kg) 18 h
      prior to experimentation, to functionally impair the sympathetic nerves,
      abolished the capsaicin-induced drop in blood pressure. Treatment of neonatal
      rats with capsaicin reduced by 75% the hypotensive effects of capsaicin, whereas
      the capsaicin antagonist, ruthenium red, reduced non-significantly the
      hypotensive action of capsaicin. It is concluded that the activation of jejunal
      sensory nerves in N. brasiliensis-sensitized rats by capsaicin induced a reflex
      hypotension that is dependent upon PAF release from mast cells and functional
      sympathetic nerves. In addition, the afferent function of the sensory nerves are
      not totally blocked by ruthenium red as capsaicin elicits the reflex hypotension
      in the presence of this blocker of sensory nerve efferent function.

PMID- 7510857
TI  - Mechanism of axonal transport. Identification of new molecular motors and
      regulations of transports.
AB  - New molecular motors associated with microtubules and actin have been uncovered
      very recently. Furthermore, studies of the mechanisms of bidirectional fast
      axonal transports have clarified new aspects of these processes, such as
      identification of a kinesin binding protein (kinectin) and regulation of kinesin
      dissociation from membranous organelles by phosphorylation. These will lead to a
      more precise understanding of the mechanisms of axonal transports. Concerning the
      mechanism of the slow transport of cytoskeletal proteins, new approaches have
      provided further evidence that the axonal cytoskeleton in mammalian systems is
      largely stationary while dynamic exchanges occur between polymer and a small pool
      of moving subunits.

PMID- 7510858
TI  - Oculomotor parasympathetic pathway to the accessory ciliary ganglion bypassing
      the main ciliary ganglion by way of the trigeminal nerve.
AB  - When an HRP or WGA-HRP solution was injected into the rostral midbrain including
      the oculomotor visceral nuclei, densely distributed HRP/WGA-HRP-positive granules
      were observed around the ganglion neurons in the accessory ciliary ganglion (ACG)
      and ectopic neurons in the communicating branch from the long ciliary nerve to
      the ACG. The same injections labeled fibers within the communicating branch as
      well as the fibers between the ACG and the main ciliary ganglion (CG). These
      findings indicate that some oculomotor parasympathetic preganglionic fibers reach
      the ACG bypassing the CG by way of the trigeminal nerve.

PMID- 7510859
TI  - Neurodevelopmental disorders and diseases.
AB  - Research on cerebral palsy--and related neurodevelopmental disorders--should
      ultimately aim at primary prevention, and, following examination of existing
      knowledge of causes and mechanisms of origin, a comprehensive and strategic
      approach to causes and mechanisms is needed.

PMID- 7510861
TI  - From nursing service to professional practice.
AB  - Tracing the evolution of a professional practice model of nursing care is the
      focus of this article. Many conditions over the past 10 years have required
      changes in the way nurses plan and deliver patient care. The way in which
      proactive strategies were developed and implemented in a large community hospital
      demonstrates how nurse administrators can build upon current systems.

PMID- 7510860
TI  - Nutrition and neurodevelopmental disorders.
AB  - Since the 1960s the structural requirements for the growth, development and
      function of the brain have become better understood due to the recognition of the
      prodigious energy needs for brain development and its structural requirements for
      lipids. The most vulnerable period of neural development is during embryonic and
      fetal growth. There is now both retrospective and prospective evidence that
      maternal nutrition prior to conception is most important to pregnancy outcome.
      Our studies on maternal nutrition in pregnancy again illustrate the relationship
      of maternal nutrition to birthweight and head circumference. In a study of 513
      pregnancies we found that nutrient intakes in mothers of low birthweight babies
      were well below those of mothers whose babies were in the 3.5-4.5 Kg range at
      which morbidity is at its lowest. Nutrient intakes tracked with birthweight,
      independent of smoking and alcohol up to, but not above 3,270 g. The closest
      correlations were obtained with the diet of the mother at or about the time of
      conception rather than later in the pregnancy. Our studies also reveal that
      premature and intrauterine growth retarded babies were born with deficits of the
      types of essential fatty acids (arachidonic AA, docosahexaenoic DHA acids) known
      to be required for brain development. Deficits of brain DHA have been found
      experimentally to impair visual and cognitive development and also to cause
      haemorrhage, not unlike peri-ventricular haemorrhage in low birthweight babies,
      the above evidence is suggestive of a route to test the prevention and treatment
      of these types of membrane related disorders.

PMID- 7510862
TI  - Endothelial cell changes in endotoxin-induced uveitis.
AB  - Modifications in endothelial cells density and variations in endothelial
      pleomorphism during experimental uveitis were studied in 20 albino rabbits after
      intravitreal injection of 2,000 ng Salmonella typhi endotoxin into 10 of them.
      The other 10 rabbits were injected with sterile saline serum. Morphologic changes
      in endothelial cells were also determined, using a method of endothelial vital
      staining. For the first time, a significant reduction in endothelial density and
      a significant increase in endothelial pleomorphism during endotoxin-induced
      uveitis is reported. The control group eyes showed an endothelial density of
      3,959 cells/mm2, while the uveitis eyes showed 3,667 cells/mm2 (p < 0.05,
      Student's t test). A reduction in the percentage of hexagonal endothelial cells
      was found, from 70.4% in the control group to 64.4% in the eyes with anterior
      uveitis (p < 0.001, Student's t test). An increase in the percentage of
      pentagonal endothelial cells was also found, from 14.5% in the control group to
      20.1% in the uveitis eyes (p < 0.001, Student's t test). These modifications are
      correlated with the morphologic appearance of the stained corneal surface, and
      functional implications are discussed.

PMID- 7510856
TI  - Dual action of angiotensin II on coronary resistance in the isolated perfused
      rabbit heart.
AB  - We studied the functional role of angiotensin II (AII) receptor subtypes and
      vasodilatory endothelial autacoid release in response to AII in isolated perfused
      rabbit hearts. AII infusion induced biphasic changes in coronary perfusion
      pressure (CPP): an initial increase was followed by a decrease until a plateau
      was reached. At higher concentrations of AII (> or = 10 nmol/l) this plateau
      phase was lower than the initial CPP level. AII infusion elicited inverse changes
      in peak left ventricular pressure (LVP): coronary constriction was associated
      with a transient decline, and during the plateau phase LVP was clearly increased.
      AII also moderately augmented prostacyclin (PGI2) release from the coronary
      vascular bed. The AII-induced changes in CPP, LVP, and PGI2 release were
      effectively inhibited by the AT1 receptor subtype antagonist ICI D8731 (30
      nmol/l), but not by the AT2 receptor antagonist CGP 42112 (30 nmol/l). The
      adenosine A1 receptor antagonist 8-phenyltheophylline (0.1 mumol/l) attenuated
      the decline in CPP following the constriction phase without affecting the changes
      in LVP during AII infusion. The cyclooxygenase inhibitor diclofenac (1 mmol/l)
      had no effect on the AII-induced changes in CPP, whereas the nitric oxide
      synthase inhibitor NG-nitro-L-arginine (30 mumol/l) markedly potentiated the
      vasoconstriction but was without effect on the plateau phase of the response. In
      contrast to AII, the thromboxane analogue U46619 elicited sustained increases in
      CPP which were associated with slight decreases in LVP.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7510864
TI  - p53 undergoes epitopic changes in vitro by sodium-vanadate.
AB  - p53 has at least two conformations that differ in their immunoreactivity. They
      consist of the functional tumor suppressor form, characteristic of the wild type
      p53 and the mutant form, generated by changes in the primary amino acid sequence
      of the protein. It has been previously shown that the wild type p53 protein also
      acquires the mutant conformation upon certain changes in growth conditions. Here
      we report that similar epitopic changes can be induced in crude cell lysate by
      addition of vanadate anions at 1 mM final concentration. A panel of anti p53
      antibodies was used to discriminate between the different immunoreactive forms of
      wild type p53 in SV80 fibroblasts. It was found that addition of sodium vanadate
      to the lysis buffer converted part of p53 molecules into a mutant conformation
      that is recognized by the PAb 240 monoclonal antibodies. The effect of vanadate
      on p53 conformation was prominent even if it was added to the cell lysates after
      15 min of pre-incubation at 37 degrees C. This further excluded its possible role
      as phosphatase inhibitor in the system and suggested a direct interaction with
      the p53 protein itself. Based on these data we recommend to avoid using sodium
      vanadate as a phosphatase inhibitor in experiments where in vivo conformational
      changes of wild type p53 are studied.

PMID- 7510863
TI  - Induction of transformation progression in type 5 adenovirus-transformed rat
      embryo cells by a cloned protein kinase C beta 1 gene and reversal of progression
      by 5-azacytidine.
AB  - Protein kinase C (PKC) is a key component in signal transduction in eucaryotic
      cells and when specific PKC isoforms are over-expressed in immortal mammalian
      cells they can induce transformation-associated properties. In the present study
      we demonstrate that a cloned PKC beta 1 gene can induce an enhanced expression of
      the transformed phenotype in type 5 adenovirus (Ad5)-transformed rat embryo (RE)
      cells (clone E11), a process termed transformation progression. E11 cells
      expressing the PKC beta 1 gene, clone B1/PKC, produce PKC beta 1 mRNA and display
      enhanced PKC enzymatic activity and binding of [3H]-phorbol-12,13-dibutyrate
      (PDBu) to cell surface phorbol ester receptors. B1/PKC cells grow with increased
      efficiency in agar in comparison with parental E11 cells and anchorage
      independence is further enhanced in both cell types by addition of the tumor
      promoting agent 12-0-tetradecanoyl-phorbol-13-acetate (TPA). A single-exposure of
      B1/PKC cells to 5-azacytidine (AZA), followed by growth in the absence of this
      demethylating agent, results in B1/PKC-AZA clones which display a stable
      reversion of the progression phenotype to that of the unprogressed parental E11
      clone. Loss of the progression phenotype corresponds with a reduction in PKC beta
      1-induced biochemical and cellular changes. In contrast, progression-suppression
      does not involve an alteration in expression of the Ad5 transforming genes, E1A
      and E1B, or the endogenous PKC epsilon gene. TPA cannot induce the progression
      phenotype in B1/PKC-AZA cells, but it can reversibly induce an increase in the
      transcriptional rate and steady-state mRNA levels of PKC beta 1 and c-jun and it
      increases AP-1 DNA-binding. These results indicate that the PKC beta 1 gene can
      serve as a transformation progression-inducing gene in rat embryo cells
      previously transformed by Ad5 and progression may be mediated by the inactivation
      by methylation of an AZA-sensitive 'progression suppressor gene(s)'. The
      suppression process in B1/PKC cells is independent of expression of the Ad5
      transforming genes but correlates directly with the reduced expression of the
      transfected PKC beta 1 gene in AZA-treated B1/PKC cells.

PMID- 7510866
TI  - Expression of cytokeratins 13 and 16 in middle ear cholesteatoma.
AB  - The accumulation of keratinizing epithelium in the middle ear cavity is a crucial
      factor in the pathogenesis of cholesteatoma. We hypothesize that keratinocytes
      from the skin of the ear canal migrate and hyperproliferate in response to
      inflammation in the middle ear cavity to cause accumulation of keratin debris. In
      the present study, we investigated the expression of specific cytokeratins (CKs)
      in the cholesteatoma matrix to determine whether cholesteatoma is a
      hyperproliferative disease. Cytokeratin expression was examined in cholesteatoma,
      meatal skin, and tympanic membrane with two monoclonal antibodies, one for both
      cytokeratins 13 and 16 (antibody K8.12), and another for cytokeratin 13 only
      (antibody KS-1A3). CK 13 (MW 51 KD) is a marker of differentiation and CK 16 (MW
      48 KD) is a marker of hyperproliferation of keratinocytes. The use of immunoblot
      probes showed that CKs 13 and 16 were present in cholesteatoma. Immunofluorescent
      staining showed the presence of CK 16 in the suprabasal layer of cholesteatoma,
      which was located near the external ear canal. CK 13 was localized in the
      suprabasal layer of meatal skin and tympanic membrane. CK 13 was localized in the
      basal layer of the cholesteatoma, distal to the external ear canal, but not in
      the meatal skin and tympanic membrane. Taken together, the present data suggest
      that cholesteatoma is a hyperproliferative disease and that cholesteatoma
      expresses CK 16 near the external ear canal and transforms to express CK 13
      during growth distally.

PMID- 7510865
TI  - Structure and expression of Spk-1, an src-related gene product found in the
      planarian Dugesia (G) tigrina.
AB  - A cDNA clone encoding a 497 amino acid protein 75% similar to most Src proteins
      has been isolated from the planarian Dugesia (Girardia) tigrina (Platyhelminthes;
      Turbellaria) by PCR followed by screening procedures. This gene product has been
      designated Spk-1 as it is the first Src-related kinase isolated in a planarian.
      The predicted amino acid sequence of Spk-1 suggest that it is anchored to the
      plasma membrane and that it interacts with other phosphotyrosine proteins. Spk-1
      is expressed in both intact and regenerating organisms as an mRNA transcript of
      about 1.9 kb. Planarians, which conserve most features of the common ancestor to
      protostomian and deuterostomian phyla, are the most primitive triploblastic
      organisms from which a protein tyrosine kinase gene product has been isolated.
      The presence of this gene product in such a primitive organism, and its presumed
      role, are discussed.

PMID- 7510867
TI  - Fetal neutrophils and eosinophils express normal levels of L-selectin.
AB  - L-selectin is a leukocyte adhesion molecule important in the initial stages of
      the interaction of neutrophils with endothelium during neutrophil emigration from
      the bloodstream. Neutrophils and eosinophils from newborn infants express
      significantly less L-selectin than do neutrophils and eosinophils from adults. It
      is not known whether L-selectin expression on fetal granulocytes is similarly
      decreased. We studied fetal blood specimens obtained for a variety of clinical
      indications by percutaneous umbilical cord sampling at 23 to 34 wk of gestation
      and measured L-selectin expression by flow cytometry. Eosinophils constituted a
      large proportion of the granulocytes in these fetal specimens (42 +/- 26%, n =
      8), with eosinophil counts ranging from 180 to 690/mm3 (mean +/- SD: 350 +/-
      220). There was no difference in L-selectin expression of unstimulated fetal and
      adult neutrophils (mean +/- SD specific fluorescence: 53.0 +/- 6.8 versus 56.6 +/
      4.3, n = 6), and no difference between unstimulated fetal and adult eosinophils
      (16.0 +/- 6.5 versus 18.7 +/- 3.2, n = 6). Thus, neutrophils and eosinophils from
      fetuses as early as 23 wk express L-selectin at adult levels. Furthermore, fetal
      neutrophils and eosinophils shed the receptor normally in response to stimulation
      in vitro. We conclude that the reduction of L-selectin expression on neonatal
      neutrophils and eosinophils is not due to an inherent developmental limitation,
      but instead must be caused by changes occurring in the neonatal period.
      Elucidation of the etiology of these changes may aid in the development of
      therapeutic measures to correct the L-selectin-related defects of neonatal
      neutrophil adherence.

PMID- 7510868
TI  - Pseudo infantile Refsum's disease: catalase-deficient peroxisomal particles with
      partial deficiency of plasmalogen synthesis and oxidation of fatty acids.
AB  - Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease
      are genetic disorders characterized by the virtual absence of catalase-positive
      peroxisomes and a general impairment of peroxisomal functions. Recent studies in
      these three disorders have provided morphologic evidence of peroxisomal "ghosts"
      of density 1.10 g/cm3 that contain membrane proteins but lack a majority of the
      matrix enzyme activities. We report here the biochemical studies in a female
      infant with clinical features of infantile Refsum's disease whose liver and
      fibroblasts contained cytosolic catalase but no catalase-positive peroxisomes.
      Oxidation of phytanic and pipecolic acids was severely impaired, whereas
      oxidation of very-long-chain fatty acids and dihydroxyacetone phosphate
      acyltransferase activity were only partially decreased. Immunoblot analysis
      showed that the three peroxisomal beta-oxidation enzymes (acyl-CoA oxidase, enoyl
      CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase) were
      detectable in liver tissues. The 3-ketoacyl-CoA thiolase was of the mature form
      (41 kD), in contrast with other peroxisomal disorders with multiple enzyme
      deficiencies. The majority of these peroxisomal enzyme activities were associated
      with two subcellular membrane vesicle fractions lacking catalase: one had the
      density of normal peroxisomes (1.17 g/cm3), the other, yet undescribed, a lower
      density (1.137 g/cm3). This suggests that peroxisomes (density = 1.17 g/cm3) and
      structures with lower density (density = 1.137 g/cm3) found in this patient's
      cultured skin fibroblasts, although lacking catalase, contained functional
      peroxisomal enzymes. This distinguishes this disorder from other disorders of
      peroxisome biogenesis.

PMID- 7510869
TI  - Pituitary adenylate cyclase activating polypeptide: a neuropeptide with potent
      inotropic and coronary vasodilatory effects in neonatal pig hearts.
AB  - Cardiac effects of the neuropeptide pituitary adenylate cyclase activating
      polypeptide (PACAP) have not previously been reported. We investigated the
      influence of PACAP, vasoactive intestinal polypeptide (68% homology with PACAP)
      and the beta-adrenergic receptor agonist isoproterenol on contractile function
      and coronary vascular tone in isolated piglet hearts (1 to 5 d of age). Paced
      (180 beats/min) isovolumically beating hearts underwent retrograde aortic
      perfusion at constant coronary flow (approximately 3 mL.min-1.g-1) with an
      erythrocyte-enriched (hematocrit 15 to 20%) solution (37 degrees C). Agonists
      were injected into the aortic root of hearts, and the positive (+) and negative (
      ) changes in maximum rate of change of systolic pressure with respect to time
      (dP/dtmax) and in coronary perfusion pressure (that reflected alterations in
      vascular tone) were measured. PACAP (n = 8, 0.1 and 0.5 nmol) increased (+)
      dP/dtmax from 944 +/- 59 to 1519 +/- 206 mm Hg/s and from 867 +/- 40 to 2010 +/-
      226 mm Hg/s (p < 0.05); increased (-) dP/dtmax from 1114 +/- 41 to 1439 +/- 95 mm
      Hg and from 999 +/- 37 to 1668 +/- 145 mm Hg/s (p < 0.05); and decreased
      perfusion pressure from 61.4 +/- 3.1 to 48.9 +/- 2.3 mm Hg and from 60.5 +/- 2.4
      to 43.9 +/- 2.3 mm Hg (p < 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510870
TI  - The effect of N omega-nitro-L-arginine methylester on hypoxic vasoconstriction in
      the neonatal pig lung.
AB  - This study was carried out to determine the influence and site of action of N
      omega-nitro-L-arginine methylester, an L-arginine analogue, on basal pulmonary
      vascular tone and hypoxic vasoconstriction in neonatal pig lungs. We studied
      isolated lungs from pigs, age 14.5 +/- 0.5 (SD) d and weight 3.6 +/- 0.7 kg,
      perfused with autologous blood at a constant flow rate. The arterial-venous
      occlusion method was used to determine sites of action upstream and downstream of
      the double occlusion pressure (Pd) during baseline, infusion of acetylcholine,
      and ventilation of the lung with a hypoxic gas mixture. The measurements were
      then repeated during the three conditions described above after adding N omega
      nitro-L-arginine methylester, a competitive inhibitor of nitric oxide synthase,
      to the blood. During control conditions, the vascular resistance was almost
      evenly divided upstream and downstream of Pd. Infusion of acetylcholine resulted
      in downstream dilation, and hypoxia resulted in an increase in both upstream and
      downstream resistance. After adding N omega-nitro-L-arginine methylester to the
      blood, there was an increase in both upstream and downstream resistances;
      acetylcholine infusion resulted in an increase in total vascular resistance,
      which was entirely due to upstream constriction; and the hypoxia response was
      much larger both upstream and downstream of Pd. These results suggest that nitric
      oxide synthase helped maintain a low level of basal pulmonary vascular tone both
      upstream and downstream of Pd in these neonatal pig lungs; that the vascular
      effect of acetylcholine was changed from downstream dilation to upstream
      constriction by N omega-nitro-L-arginine methylester; and that nitric oxide
      synthase activity modulated both the upstream and downstream vasomotor response
      to hypoxia.

PMID- 7510871
TI  - Effects of N-omega-nitro-L-arginine methyl ester on the cerebral circulation of
      newborn piglets quantified in vivo by near-infrared spectroscopy.
AB  - The effects of N-omega-nitro-L-arginine methyl ester (L-NAME) on basal cerebral
      vascular tone, the vasodilatory effects of acetylcholine (ACh), and the
      cerebrovascular response to alterations in arterial carbon dioxide tension (CBVR)
      were investigated using near-infrared spectroscopy. Seven newborn piglets were
      anesthetized and mechanically ventilated; mean arterial blood pressure (MAP) was
      monitored and near-infrared spectroscopy used to measure changes in total
      cerebral Hb concentration. At the beginning of the experiment, CBVR was measured
      and then 10, 20, 30, and 100 mg.kg-1 L-NAME were administered sequentially; ACh
      (1, 2, 3, and 5 micrograms) was given before and after each injection of L-NAME.
      At the end of this sequence, CBVR was measured again and finally sodium
      nitroprusside (1.5 mg.kg-1) was administered. Ten and 20 mg.kg-1 L-NAME caused a
      significant decrease in total cerebral Hb concentration of -0.59 (-3.21 to -0.02)
      and -1.46 (-6.50 to -0.15) mumol.L-1 (median and range), respectively (Wilcoxon p
      < 0.05), but subsequent injections did not. Ten, 20, and 100 mg.kg-1 L-NAME
      caused an increase in MAP (Wilcoxon p < 0.05). ACh caused an increase in total
      cerebral Hb concentration and a decrease in MAP that was impaired but not
      abolished by L-NAME (ANOVA p < 0.05). CBVR was not affected by L-NAME. Sodium
      nitroprusside caused a reduction in mean (SD) MAP of 4.7 (1.6) kPa, and a slower
      rise in [tHb] of 13.44 (2.03) mumol.L-1. Postmortem examination of three animals
      revealed NADPH-diaphorase staining in neurons, cerebral blood vessels, carotid
      artery, and jugular vein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510872
TI  - Developmental differences of cystic fibrosis transmembrane conductance regulator
      functional expression in isolated rat fetal distal airway epithelial cells.
AB  - Fluid secretion from the pulmonary epithelium may play a significant role in
      determining intrauterine lung development. We used suspensions of distal
      pulmonary epithelial cells isolated from rat fetuses to assess a shift in
      secretory mechanisms occurring in the lung of this species during late gestation.
      The impact of cAMP on distal airway epithelial cells isolated from d 18 to d 21
      rat fetuses was evaluated with measurements of cell volume and 36Cl efflux rates.
      At d 18, 8-Br-cAMP stimulated a volume reduction measured by electronic cell
      sizing that was prevented by the Cl- channel blocker anthracene-9-carboxylate (A
      9C) and reflected in an increased rate of A-9C sensitive 36Cl efflux. Because the
      cystic fibrosis transmembrane conductance regulator (CFTR) is thought to be a
      cAMP-regulated Cl- channel, we measured the effect of prior cell incubation with
      oligodeoxynucleotides antisense to the transcription site of the human CFTR gene
      on these events. We found that in antisense oligomer-treated cells, but not in
      sense oligomer-treated controls, volume and 36Cl efflux responses to 8-Br-cAMP
      were prevented in d 18 cells. In d 21 cells, 8-Br-cAMP did not stimulate volume
      reduction but the calcium ionophore A23187 did elicit cell volume reduction in
      cells suspended in an isotonic Ca(2+)-containing medium that was prevented by A
      9C. This response to the ionophore was not found in the d 18 cells, and
      incubation with the antisense CFTR oligomer had no effect on the ionophore
      induced responses in d 21 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510874
TI  - Preventing developmental delays: is developmental screening sufficient?

PMID- 7510873
TI  - In vitro and in vivo effects of granulocyte colony-stimulating factor on
      neutrophils in glycogen storage disease type 1B: granulocyte colony-stimulating
      factor therapy corrects the neutropenia and the defects in respiratory burst
      activity and Ca2+ mobilization.
AB  - Children with glycogen storage disease (GSD) type 1b are susceptible to recurrent
      bacterial infections and have chronic neutropenia accompanied by phagocytic cell
      dysfunction including decreased superoxide anion (O2-) generation, calcium (Ca2+)
      mobilization, and chemotactic activity. Granulocyte colony-stimulating factor (G
      CSF), a cytokine that corrects neutropenia in other diseases, in vitro enhances f
      Met-Leu-Phe-triggered neutrophil O2- generation. Short-term pretreatment (15 min)
      of GSD 1b neutrophils with G-CSF increased the rate of O2- production (p < 0.01);
      however, this rate was still significantly below the rate of O2- production in
      control neutrophils. Recombinant human G-CSF (5 micrograms/kg/d) was administered
      s.c. to a GSD 1b patient. Before treatment, absolute neutrophil counts were <
      500/mm3. Two d after G-CSF administration, the absolute neutrophil counts
      increased to 1333 and remained in the normal range during a 12-mo follow-up
      period. In vivo, G-CSF therapy increased f-Met-Leu-Phe-stimulated O2- production
      to 52% of control after 1 mo, and by mo 4, O2- production reached control levels.
      Our previous studies (J Clin Invest 56:196-202, 1990) demonstrated that decreased
      O2- production in neutrophils was associated with impaired Ca2+ mobilization. In
      vivo administration of G-CSF increased f-Met-Leu-Phe-triggered Ca2+ mobilization
      by neutrophils to 43% of control by mo 1 of G-CSF therapy and to 93% of control
      by mo 4, thus paralleling the improvements in O2- generation. In contrast, G-CSF
      therapy had no effect on the defective neutrophil chemotaxis. In summary, G-CSF
      therapy produced a rapid increase in circulating neutrophils and a gradual
      correction of O2- production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510876
TI  - Nitric oxide synthase is deficient in the aganglionic colon of patients with
      Hirschsprung's disease.
AB  - OBJECTIVES: The cause of Hirschsprung's disease is unknown but defects in
      nonadrenergic, non-cholinergic innervation could prevent relaxation of
      aganglionic colon in patients with this disease. Nonadrenergic, noncholinergic
      nerves induce relaxation by using nitric oxide synthase to produce the smooth
      muscle relaxant nitric oxide (NO). In this study we asked whether aganglionic
      colon in patients with Hirschsprung's disease is deficient in NO synthase
      containing nerves. METHODOLOGY: Using the tetrazolium blue dye method of
      demonstrating nicotinamide adenine dinucleotide phosphate-diaphorase enzymes, we
      examined eight colon specimens (four aganglionic and four ganglionic) from
      patients with Hirschsprung's disease for the presence of NO synthase. We further
      quantified NO synthase enzyme activity in these eight specimens by using the
      [3H]arginine-to-[3H]citrulline conversion assay. RESULTS: The nicotinamide
      adenine dinucleotide phosphate-diaphorase staining showed that aganglionic colon
      contained less NO synthase than ganglionic colon. This NO synthase deficiency was
      located primarily in the nerves of the circular muscle layer of the colon. In
      addition, there was a striking difference in the NO synthase enzyme activity
      between aganglionic and ganglionic colon as measured by the [3H]arginine-to
      [3H]citrulline conversion assay. Total NO synthase activity, as measured by this
      assay, was found to be less in aganglionic than in ganglionic colon. When the
      total activity was divided into its four known isoforms, aganglionic colon was
      noted to be striking deficient in the isoform derived primarily from nerves.
      CONCLUSION: We conclude that aganglionic colon is deficient in NO synthase
      containing nerves. This deficiency could prevent smooth muscle relaxation in the
      aganglionic colon of patients with Hirschsprung's disease.

PMID- 7510875
TI  - Outcome of very low birth weight infants: multiple gestation versus singletons.
AB  - OBJECTIVE: Multiple gestation infants are overrepresented in intensive care
      nurseries, and have been reported to have greater morbidity than singletons. A
      cohort of very low birth weight infants was examined to determine outcome of
      premature infants based on gestation type (multiple or single) and hypothesized
      that at this low birth weight, the outcome of the groups would be similar.
      METHOD: The sample was composed of all infants with birth weights < or = 1250 g
      born in a 10-year period (September 1977 through September 1987). Ninety-two
      percent (n = 364) of the infants discharged were seen at 1 year of age, and 73%
      (n = 249) were observed to school age. Morbidity was assessed by
      neurodevelopmental examinations and standard developmental tests. RESULTS: At 1
      year of age and at school age, there were no differences in neurologic or
      neurosensory outcome between multiple gestation and single gestation infants.
      Logistic regression analyses were performed on the school age data, using
      cognitive outcome as the dependent variable and gestation type, birth weight,
      gestational age, intracranial hemorrhage, chronic lung disease, and a social risk
      factor as predictor variables. Gestation type was not associated with cognitive
      outcome at school age. Social risk factors and chronic lung disease showed an
      association with cognitive outcome at school age. CONCLUSIONS: Multiple gestation
      was not related to increased morbidity in this very low birth weight group. The
      developmental outcome of all infants with birth weights < or = 1250 g in this
      study was related to medical and social risk factors. These findings were
      consistent for a large group of infants over a 10-year period.

PMID- 7510877
TI  - Inactivation of the murine cftr gene abolishes cAMP-mediated but not Ca(2+)
      mediated secretagogue-induced volume decrease in small-intestinal crypts.
AB  - The cellular volume of crypts isolated from 2- to 3-week-old mouse small
      intestine has been measured to assess the capacity of the epithelial cells to
      respond to secretagogues. Vasoactive intestinal polypeptide (VIP) or carbachol,
      respectively cAMP- and calcium-mediated secretagogues, produced a reduction crypt
      volume attributed to KCl loss through channels activated by the agonists.
      Consistent with the participation of separate chloride channels, 4,4'
      diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) blocked the carbachol- but
      not the VIP-induced volume decrease, whilst glibenclamide abolished the VIP
      effect without affecting the carbachol-induced volume decrease. Animals
      homozygous for a disrupted cftr gene, introduced by gene targeting, were also
      used as the source for crypt isolation. In these CFTR (-/-) crypts. VIP failed to
      elicit any reduction in cellular volume, while the response to carbachol was
      indistinguishable from that seen in crypts from age-matched control animals.
      These results are consistent with murine CFTR being a cAMP-activated chloride
      channel inhibited by glibenclamide and resistant to DIDS. A separate chloride
      conductance activated by calcium mobilization in small-intestinal crypts appears
      to be independent of CFTR.

PMID- 7510879
TI  - Calcium permeability of nicotinic acetylcholine receptor channels in bovine
      adrenal chromaffin cells.
AB  - The fractional contribution of Ca to current flow through neuronal-type nicotinic
      acetylcholine receptor channels was determined by quantitative fluorescence
      microfluorimetry using fura-2. The method, which has been applied already to
      several types of cells and channels is described in detail here. At -70 mV and 2
      mM external Ca concentration it was found that Ca contributes 2.5% to the net
      current. The fractional contribution was found to be voltage dependent,
      increasing at negative potentials e-fold for a 110 mV potential difference. Total
      non-specific cation current was found to have a bell-shaped dependence on
      external Ca concentration peaking at 2 mM.

PMID- 7510880
TI  - Reversible blockade of the calcium-activated nonselective cation channel in brown
      fat cells by the sulfhydryl reagents mercury and thimerosal.
AB  - We have used patch-clamp techniques to study the effect of the sulfhydryl group
      oxidizing agents mercury and thimerosal on calcium-activated nonselective cation
      channels from brown adipose tissue. 100 nmol/l mercury and 50 mumol/l thimerosal
      induced a complete block. Blockade could be reversed by reduction of the
      mercaptide by dithiotreitol (DTT). Mercury was found to be the most potent
      blocker (IC50-value 21 x 10(-9) mol/l), whereas thimerosal (IC50-value 1.5 x 10(
      6) mol/l) was as effective as 3',5-dichlorodiphenylamine-2-carboxylic acid
      (DCDPC). The DCDPC effect, however, could not be reversed by DTT, indicating
      different blocking mechanisms. It is concluded that SH-groups are involved in
      gating of the calcium-activated nonselective channel.

PMID- 7510878
TI  - Potentiation of acetylcholine responses in Xenopus embryonic muscle cells by
      dibutyryl cAMP.
AB  - Application of membrane-permeable analogues of adenosine 3',5'
      (cyclic)monophosphate (cAMP) or forskolin to embryonic muscle cells of 1-day-old
      Xenopus cultures altered the response of the myocyte to iontophoretically applied
      acetylcholine (ACh). The initial amplitude and the decay time of the ACh-induced
      currents were elevated, and the rate of ACh-induced channel desensitization was
      increased. Single-channel recordings showed that cAMP analogues increased the
      mean open time of the low-conductance ACh channels, without affecting the single
      channel conductance. Interestingly, this effect on ACh channels disappeared in
      myocytes of 3-day-old cultures, suggesting developmental changes in the
      susceptibility of the ACh channel to modulation. A possible involvement of cAMP
      in modulating the synaptic activity of early developing synapses was further
      indicated by prolonged decay times of spontaneous synaptic currents following
      treatment with dibutyryl-cAMP (Bt2cAMP). Factors released from the nerve
      terminals, if they activate the muscle adenylate cyclase system, could thus
      enhance the synaptic response during synaptogenesis.

PMID- 7510882
TI  - N alpha-carboxyacyl analogues of CCK with a substituted Gly: interaction with
      pancreatic and gallbladder CCK receptors.
AB  - It has been reported that certain N alpha-carboxyacyl analogues of CCK-8 and of
      CCK-7 with a substituted Gly in position 3 or 4 of the peptide possess higher
      potencies at stimulating pancreatic enzyme secretion than at stimulating
      gallbladder contraction, suggesting that these analogues are able to
      differentiate subtypes of CCKA receptors. However, no studies examined directly
      the interaction of these peptides with the CCK receptors in both tissues. In the
      present study, CCK-8 and various N alpha-carboxyacyl analogues of CCK-7 and of
      CCK-8 were prepared by solid phase synthesis using Fmoc chemistry and were
      purified by HPLC; molecular weight and sufficient sulfation were determined by
      mass spectrometry. [125I]Bolton-Hunter(BH)-CCK-8 binding to sections of the
      guinea pig pancreas and gallbladder was determined under identical conditions;
      amylase release from pancreatic acini and contraction of gallbladder muscle
      strips were measured in vitro. Each peptide stimulated amylase release (EC50):
      CCK-8 (0.09 nM) > Suc[Sar3]CCK-7 (0.23 nM) > des(SO3)CCK-8 (28 nM) > Suc[D
      Trp4]CCK-8 (32 nM) > Suc[D-Trp3]CCK-7 (53 nM) > Pht[D-Trp3]CCK-7 (180 nM) > Glt[D
      Trp3]CCK-7 (220 nM). The same relative potencies were found for stimulation of
      gallbladder contraction, and for the inhibition of [125I]BH-CCK-8 binding to
      pancreas and gallbladder sections. These data demonstrate that the CCKA receptors
      in the pancreas and on gallbladder smooth muscle possess similar affinities for
      the various N alpha-carboxyacyl analogues of CCK-7 and CCK-8 with a substituted
      Gly and provide further evidence that the CCKA receptors in gallbladder and
      pancreas cannot be distinguished pharmacologically.

PMID- 7510881
TI  - CGRP antagonists and capsaicin on celiac ganglia partly prevent postoperative
      gastric ileus.
AB  - The role of capsaicin-sensitive pathways and CGRP in postoperative gastric ileus
      was investigated. Abdominal surgery was performed under enflurane anesthesia, and
      5 min later, the 20-min rate of gastric emptying was measured by the phenol red
      method in conscious rats. Surgery inhibited gastric emptying by 76-83% compared
      with rats receiving anesthesia alone. Capsaicin on the celiac/mesenteric ganglia
      (10-21 days before) reduced gastric ileus by 33 +/- 8%, whereas perivagal
      capsaicin had no effect. The IV CGRP-induced inhibition of gastric emptying was
      completely reversed by the CGRP antagonist, CGRP(8-37) (30 micrograms, IV);
      CGRP(8-37) (15, 30, or 60 micrograms) or CGRP monoclonal antibody #4901 (2 mg
      protein) decreased the inhibition of gastric emptying by 11 +/- 7%, 51 +/- 13%,
      47 +/- 3%, and 45 +/- 17%, respectively. These results indicate that CGRP and
      splanchnic capsaicin-sensitive afferents are involved in mediating part of the
      gastric ileus observed immediately after abdominal surgery.

PMID- 7510884
TI  - Ribozyme-mediated attenuation of pancreatic beta-cell glucokinase expression in
      transgenic mice results in impaired glucose-induced insulin secretion.
AB  - Phosphorylation of glucose to glucose 6-phosphate by glucokinase (GK; EC 2.7.1.2)
      serves as a glucose-sensing mechanism for regulating insulin secretion in beta
      cells. Recent findings of heterozygous GK gene mutations in patients with
      maturity-onset diabetes of the young (MODY), a form of type II (non-insulin
      dependent) diabetes characterized by autosomal dominant inheritance, have raised
      the possibility that a decrease in beta-cell GK activity may impair the insulin
      secretory response of these cells to glucose. To generate an animal model for
      MODY we have expressed in transgenic mice a GK antisense RNA with a ribozyme
      element under control of the insulin promoter. Mice in two independent lineages
      had about 30% of the normal islet GK activity. Insulin release in response to
      glucose from in situ-perfused pancreas was impaired; however, the plasma glucose
      and insulin levels of the mice remained normal. These mice are likely to be
      predisposed to type II diabetes and may manifest increased susceptibility to
      genetic and environmental diabetogenic factors. They provide an animal model for
      studying the interaction of such factors with the reduced islet GK activity.

PMID- 7510883
TI  - Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation.
AB  - Cyclooxygenase (COX) converts arachidonic acid to prostaglandin H2, which is
      further metabolized to prostanoids. Two isoforms of COX exist: a constitutive
      (COX-1) and an inducible (COX-2) enzyme. Nitric oxide is derived from L-arginine
      by isoforms of nitric-oxide synthase (NOS; EC 1.14.13.39): constitutive (cNOS;
      calcium-dependent) and inducible (iNOS; calcium-independent). Here we have
      investigated inducible isoforms of COX and NOS in the acute, chronic, and
      resolving stages of a murine air pouch model of granulomatous inflammation. COX
      and NOS activities were measured in skin samples in the acute phase, up to 24 h.
      Activities in granulomatous tissue were measured at 3, 5, 7, 14, and 21 days for
      the chronic and resolving stages of inflammation. COX-1 and COX-2 proteins were
      assessed by Western blot. COX activity in the skin increased over the first 24 h
      and continued to rise up to day 14. COX-2 protein rose progressively, also
      peaking at day 14. COX-1 protein remained unaltered throughout. The iNOS activity
      increased over the first 24 h in the skin, with a further major increase in the
      granulomatous tissue between days 3 and 7, followed by a decrease at day 14 and a
      further increase at day 21. The rise in COX and NOS activities in the skin during
      the acute phase reinforces the proinflammatory role for prostanoids and suggests
      one also for nitric oxide. However, in the chronic and resolving stages, a
      dissociation of COX and NOS activity occurred. Thus, there may be differential
      regulation of these enzymes, perhaps due to the changing pattern of cytokines
      during the inflammatory response.

PMID- 7510885
TI  - Induction of anti-tumor cytotoxic T lymphocytes in normal humans using primary
      cultures and synthetic peptide epitopes.
AB  - Cytotoxic T lymphocytes (CTLs) recognize peptide antigens associated with cell
      surface major histocompatibility complex (MHC) molecules. The identification of
      tumor cell-derived peptides capable of eliciting anti-tumor CTL responses would
      enable the design of antigen-specific immunotherapies. Our strategy to identify
      such potentially therapeutic peptides relies on selecting high-affinity MHC
      binders from known tumor-associated antigens. These peptides are subsequently
      tested for their ability to induce CTLs capable of killing tumor cells. With this
      strategy, we have identified a nine-residue epitope, derived from the product of
      the tumor-associated gene MAGE-3, which has the capacity to induce in vitro CTLs
      that kill melanoma and other tumor cell lines. These results show the primary in
      vitro induction of tumor-specific human CTLs and illustrate the feasibility of ex
      vivo antigen-specific approaches to the immunological therapy of cancer.

PMID- 7510886
TI  - Ribosome binding of DNA analogs of tRNA requires base modifications and supports
      the "extended anticodon".
AB  - The efficiency of translation depends on correct tRNA-ribosome interactions. The
      ability of chemically synthesized yeast tRNA(Phe) anticodon domains to
      effectively inhibit the binding of native yeast tRNA(Phe) to poly(U)-programmed
      Escherichia coli 30S ribosomal subunits was dependent on a Mg(2+)-stabilized stem
      and an open anticodon loop, both facilitated by base modifications. Analysis of
      tRNA sequences has revealed that base modifications which negate canonical
      hydrogen bonding are found in 95% of those tRNA anticodon loop sequences with the
      potential to form two Watson-Crick base pairs across the loop. Therefore, we
      postulated that a stable anticodon stem and an open loop are prerequisites for
      ribosome binding. To test this hypothesis, DNA analogs of the yeast tRNA(Phe)
      anticodon domain were designed to have modification-induced, Mg(2+)-stabilized
      stems and open loops. The unmodified DNA analog neither bound to poly(U)
      programmed 30S ribosomal subunits nor inhibited the binding of native tRNA(Phe).
      However, specifically modified DNA analogs did bind to ribosomal subunits and
      effectively inhibited tRNA(Phe) from binding. Thus, modification-dependent Mg(2+)
      stabilized anticodon domain structures with open loops have evolved as the
      preferred anticodon conformations for ribosome binding.

PMID- 7510887
TI  - Existence of nitric oxide synthase in rat hippocampal pyramidal cells.
AB  - It has been proposed that nitric oxide (NO) serves as a key retrograde messenger
      during long-term potentiation at hippocampal synapses, linking induction of long
      term potentiation in postsynaptic CA1 pyramidal cells to expression of long-term
      potentiation in presynaptic nerve terminals. However, nitric oxide synthase
      (NOS), the proposed NO-generating enzyme, has not yet been detected in the
      appropriate postsynaptic cells. We here demonstrate specific NOS immunoreactivity
      in the CA1 region of hippocampal sections by using an antibody specific for NOS
      type I and relatively gentle methods of fixation. NOS immunoreactivity was found
      in dendrites and cell bodies of CA1 pyramidal neurons. Cultured hippocampal
      pyramidal cells also displayed specific immunostaining. Control experiments
      showed no staining with preimmune serum or immune serum that was blocked with
      purified NOS. These results demonstrate that CA1 pyramidal cells contain NOS, as
      required were NO involved in retrograde signaling during hippocampal synaptic
      plasticity.

PMID- 7510888
TI  - Correction of accelerated autoimmune disease by early replacement of the mutated
      lpr gene with the normal Fas apoptosis gene in the T cells of transgenic MRL
      lpr/lpr mice.
AB  - MRL-lpr/lpr mice develop a generalized autoimmune disease which includes
      increased autoantibody production, glomerulonephritis, and development of
      lymphadenopathy. The lpr genetic defect has been identified as a mutation in the
      Fas apoptosis gene that results in low expression of Fas mRNA. To determine the
      significance of the lpr mutation and T cells in the development of the autoimmune
      disease, we constructed transgenic MRL-lpr/lpr mice using a full-length murine
      Fas cDNA under the regulation of the T-cell-specific CD2 promoter and enhancer.
      Here we show that the early correction of the lpr gene defect in T cells
      eliminates glomerulonephritis and development of lymphadenopathy and decreases
      the levels of autoantibodies. In this model, early correction of the lpr defect
      in T cells is sufficient to eliminate the acceleration of autoimmune disease even
      in the presence of B cells and other cells that express the mutant lpr gene.

PMID- 7510889
TI  - Ca2+ influx through stretch-activated cation channels activates maxi K+ channels
      in porcine endocardial endothelium.
AB  - The endocardial endothelium is an important modulator of myocardial function. The
      present study demonstrates the existence of a stretch-activated Ca(2+)-permeable
      cation channel and of a Ca(2+)-activated K+ channel in the endocardial
      endothelium of the porcine right atrium. The stretch-activated channel is
      permeable for K+, Na+, Ca2+, and Ba2+, with mean conductances of approximately 32
      pS for the monovalent cations and approximately 13 pS for divalent cations. The
      Ca(2+)-activated K+ channel has a mean conductance of 192 pS in symmetrical KCl.
      solution. Channel activity is strongly dependent on membrane potential and the
      cytosolic Ca2+ concentration. Half-maximal activation occurs at a cytosolic Ca2+
      concentration of approximately 5 microM. The influx of Ca2+ through the stretch
      activated channel is sufficient to activate the Ca(2+)-activated K+ channel in
      cell-attached patches. Upon activation of the stretch-activated channel, the
      cytosolic Ca2+ concentration increases, at least locally, to values of
      approximately 0.5 microM, as deduced from the open probability of the Ca(2+)
      dependent K+ channel that was activated simultaneously. The stretch-activated
      channels are capable of inducing an intracellular Ca2+ signal and may have a role
      as mechanosensors in the atrial endothelium, possibly activated by atrial
      overload.

PMID- 7510891
TI  - Effects of stinging nettle root extracts and their steroidal components on the
      Na+,K(+)-ATPase of the benign prostatic hyperplasia.
AB  - The effects of organic-solvent extracts of Urtica dioica (Urticaceae) on the
      Na+,K(+)-ATPase of the tissue of benign prostatic hyperplasia (BPH) were
      investigated. The membrane Na+,K(+)-ATPase fraction was prepared from a patient
      with BPH by a differential centrifugation of the tissue homogenate. The enzyme
      activity was inhibited by 10(-4)-10(-5) M of ouabain. The hexane extract, the
      ether extract, the ethyl acetate extract, and the butanol extract of the roots
      caused 27.6-81.5% inhibition of the enzyme activity at 0.1 mg/ml. In addition, a
      column extraction of stinging nettle roots using benzene as an eluent afforded
      efficient enzyme inhibiting activity. Steroidal components in stinging nettle
      roots, such as stigmast-4-en-3-one, stigmasterol, and campesterol inhibited the
      enzyme activity by 23.0-67.0% at concentrations ranging from 10(-3)-10(-6) M.
      These results suggest that some hydrophobic constituents such as steroids in the
      stinging nettle roots inhibited the membrane Na+,K(+)-ATPase activity of the
      prostate, which may subsequently suppress prostate-cell metabolism and growth.

PMID- 7510890
TI  - Biochemical studies on capped RNA primers identify a class of oligonucleotide
      inhibitors of the influenza virus RNA polymerase.
AB  - A synthetic 67-nt RNA substrate, containing a 32P-labeled cap-1 structure
      (m7G32pppGm) was specifically cleaved by the influenza virus RNA polymerase (EC
      2.7.7.48) to yield a single capped 11-nt fragment capable of directly priming
      transcription. An analysis of systematic truncations of this RNA substrate
      demonstrated that an additional nucleotide beyond this cleavage site was required
      for cleavage. The minimal RNA chain length required for priming activity was
      found to be 9 nt, while in contrast an RNA chain length of at least 4 nt was
      required for efficient binding to the viral polymerase. On the basis of these
      chain length requirements we show that a pool of capped oligonucleotides too
      short to prime transcription, but long enough to bind with high affinity to the
      viral polymerase, are potent inhibitors of cap-dependent transcription in vitro.

PMID- 7510892
TI  - The roles of revascularization and resorption on endurance of craniofacial onlay
      bone grafts in the rabbit.
AB  - A total of 32 New Zealand white rabbits underwent subperiosteal implantation of
      fresh autogenous unicortical calvarial and iliac crest grafts on their snouts
      with microscrew rigid fixation. After 3 and 10 days, vascularity was assessed by
      latex casting, and osteoclastic activity was determined by histochemical staining
      for tartrate-resistant acid phosphatase. After 70 days, volumetric analysis and
      tartrate-resistant acid phosphatase staining were performed on six animals. The
      calvarial grafts demonstrated greater volume maintenance than the iliac bone (72
      percent versus 32 percent, p < 0.025). There were significantly greater
      osteoclastic activity and revascularization in the cancellous portion of
      calvarial and iliac crest bone grafts by the 10th day of onlay grafting. Minimal
      activities were present at the cortical bone. Because calvarial grafts contain
      more cortical bone, its superior volume maintenance can be understood by the
      architectural influence on revascularization and resorption.

PMID- 7510893
TI  - DNA double-strand breakage by bleomycin in Ehrlich ascites tumor cells as
      measured by nondenaturing filter elution.
AB  - DNA double-strand breakage by bleomycin (Bleo) in Ehrlich ascites tumor cells was
      examined by nondenaturing filter elution using 0.2% SDS at pH 9.6 as the eluant.
      The majority of damaged DNA from cells treated with 5 to 100 microM Bleo and for
      durations up to 6 h eluted in the first two or three 1.5-h fractions. This was
      significantly different from the multiphasic elution pattern of DNA from cells
      irradiated with 30 or 50 Gy 137Cs gamma rays, which showed a more gradual
      elution. Relative elution with respect to 50 Gy 137Cs gamma rays produced by 1-h
      treatments (about 0.35) showed no differences over the range of concentrations
      from 5 to 50 microM. Elution at pH 7.2 did not detectably reduce the fraction of
      DNA eluting from Bleo-treated cells, while reducing the elution of DNA from 50 Gy
      irradiated cells by 35%. An experiment examining specificity for double-strand
      breakage by Bleo in different stages of the cell cycle demonstrated no
      differences in relative elution between G1, S and G2/M phases. Overall, the
      results of 1-h treatments are consistent with net production of high levels of
      double-strand breaks restricted to a portion of cellular DNA. However, extended
      treatments (up to 4 h) produced a nearly proportional increase in relative
      elution.

PMID- 7510894
TI  - Comparative effects of gamma rays and electron beams on spores of Bacillus
      pumilus.
AB  - The effects of gamma rays and electron beams on the germination, outgrowth and
      the synthesis of protein and RNA of Bacillus pumilus spores were investigated to
      clarify the difference in the effects of the two types of radiations on bacterial
      spores. Gamma irradiation facilitated the germination to a slightly larger degree
      than electron irradiation. The outgrowth, growth and the synthesis of protein and
      RNA were inhibited by gamma irradiation to a greater extent than electron
      irradiation, when the spores were irradiated at the same dose. However, the
      effects of the two types of radiations were the same when the spores were
      irradiated with electron beams at a dose 30% higher than gamma rays. The results
      indicate that the effects of electron beams on bacterial spores and those of
      gamma rays are qualitatively the same but quantitatively different.

PMID- 7510896
TI  - Follow-up of benign hypoechoic peripheral zone lesions of the prostate gland: US
      characteristics and cancer prevalence.
AB  - PURPOSE: To evaluate the role of biopsy-proved benign peripheral zone hypoechoic
      lesions of the prostate gland, ultrasonographic (US) characteristics at follow
      up, prostate-specific antigen (PSA) levels, and digital rectal examination (DRE)
      in prediction of cancer risk. MATERIALS AND METHODS: Retrospective analysis was
      performed for 105 consecutive patients with 148 benign hypoechoic lesions
      discovered at transrectal US (TRUS) and diagnosed with US-guided needle biopsy.
      At least one repeat TRUS study was performed in each patient. RESULTS: Among the
      benign lesions, 72% changed at follow-up TRUS, either disappearing or becoming
      smaller, less hypoechoic, and more vague. Cancer developed in 13% of patients. In
      93% of patients in whom cancer developed, the appearance changed in the
      peripheral zone at follow-up TRUS. In this patient population, the positive
      predictive value for development of cancer was 16% with a changing TRUS
      appearance, 19% with an abnormal DRE result, and 27% with an elevated level of
      PSA; only the latter was statistically significant. CONCLUSION: The PSA value,
      alone or in combination with a changing TRUS appearance, is the best indicator
      for development of cancer.

PMID- 7510895
TI  - Bleomycin-induced fibrosis in pigs: evaluation with CT.
AB  - PURPOSE: To establish an animal model for use in evaluation of early morphologic
      changes of pulmonary fibrosis by means of precise correlation of findings at thin
      section computed tomography (CT) and pathologic findings. MATERIALS AND METHODS:
      Bleomycin (1.0-2.5 U per kilogram of body weight) was delivered selectively into
      the left lower lobe bronchus via balloon catheter in five Yorkshire pigs.
      Sequential CT examinations were performed at regular intervals. The animals were
      killed at follow-up of 5 days to 4 weeks. At autopsy, the lungs were removed,
      inflated, fixed and dried, and subsequently sliced into sections that
      corresponded to the CT sections. The fixed lungs were examined with thin-section
      CT, radiography, and histologic studies. RESULTS: There was good correlation
      between pathologic findings at CT and specimen radiography. Histologic study
      revealed signs of pneumonitis and developing fibrosis. CONCLUSIONS: This disease
      model is suitable for radiologic and pathologic evaluation of interstitial
      fibrosis. CT was sensitive in detection of bleomycin-induced abnormalities.

PMID- 7510898
TI  - Culture filtrate proteins of Dermatophilus congolensis.
AB  - In previous studies on the antigens of Dermatophilus congolensis very little
      attention has been given to the hyphae and to excreted-secreted products (ESP) of
      actively growing bacteria. In this study we have grown four isolates of D.
      congolensis in a serum free synthetic liquid culture medium based on RPMI 1640.
      Diafiltration and ultrafiltration were used to prepare ESP from infected culture
      fluid. These methods produced sufficient quantities of ESP that the polypeptide
      profiles of the four isolates could be examined by SDS-PAGE and Western
      immunoblotting. The four isolates produced a large number of polypeptides in
      culture, most of which were produced by all four isolates. However each isolate
      produced polypeptides that were unique to it. Western immunoblotting studies
      using pooled sera from chronically affected animals from Ghana showed that a
      number of polypeptides in ESP of a Ghanaian isolate were antigenic. When the same
      sera was tested against ESP from a Scottish isolate a number of polypeptides of
      the same molecular weight as those in the Ghanaian isolate and some at different
      molecular weights were recognized. This indicates that isolates of D. congolensis
      from different geographical areas produce ESP with shared antigenic determinants.

PMID- 7510899
TI  - Role of interferons in infectious diseases in the bovine species: effect on
      viruses and rickettsias.
AB  - Successful protection was obtained with interferon treatment in experimental
      viral infections in the bovine species in a number of cases. The efficacy of the
      treatment against vaccinia virus infection and against rotavirus infection have
      been demonstrated. On the contrary, bovine herpes virus 1 (BHV 1-causing
      rhinotracheitis and part of the shipping fever complex) infections were not
      inhibited by interferon (IFN). The authors have undertaken a study in cattle in
      Zimbabwe to assess the role of interferon in the resistance of the animals to
      Cowdria ruminantium. A good correlation between production of interferon by the
      animal following the infection, and the resistance of the animals against the
      rickettsia was demonstrated. This pointed out the possible "adjuvant" role of
      interferons and other cytokines.

PMID- 7510897
TI  - Budesonide inhibits plasma extravasation induced by capsaicin and by substance P
      in the rat nasal mucosa.
AB  - We studied the effect of the locally administered glucocorticoid budesonide on
      plasma extravasation induced by capsaicin and by substance P (SP) in the nasal
      mucosa of pathogen-free rats. Using Evans blue dye as a tracer, we measured
      plasma extravasation induced by capsaicin (150 micrograms kg-1 i.v.) or SP (0.5
      and 2.5 micrograms kg-1 i.v.) in the rat naso- and maxilloturbinates after
      pretreatment with budesonide (0.1-50 micrograms twice/day for 2 days in the right
      nostril; 50 micrograms only for SP) or its vehicle. We found that budesonide
      inhibits plasma extravasation induced by capsaicin in a dose-dependent fashion in
      the nasal cavity. After the highest dose (50 micrograms) of budesonide, the
      values of Evans blue in the nasal mucosa were not different from the values
      observed after capsaicin vehicle alone. Budesonide also reduced plasma
      extravasation induced by capsaicin in the trachea and the urinary bladder of the
      rats in a dose-dependent fashion. Budesonide (50 micrograms) delivered to the
      nose inhibited the plasma extravasation caused by 0.5 but not by 2.5 micrograms
      SP kg-1 in the nasal mucosa. We conclude that the postjunctional part of the
      neurogenic pathway is a target for glucocorticoid antiinflammatory action in the
      nasal mucosa, at least of the rat. Budesonide's effect on organs other than the
      nose can be explained by systemic absorption.

PMID- 7510901
TI  - [Perspectives in urology].

PMID- 7510902
TI  - [Feeding the terminal patient].

PMID- 7510903
TI  - Characterization of mouse monoclonal antibodies against common and repeated
      epitopes of different developmental stages of Schistosoma mansoni.
AB  - Eight IgM monoclonal antibodies (mAbs) obtained from a Schistosoma mansoni
      chronically infected mouse immunized twice with adult worms butanolic extract
      (BE) and soluble egg antigen (SEA) were characterized by immunochemical methods.
      An intense cross-reactivity between different developmental stages was observed
      by indirect immunofluorescence assay (IIFA) with five anti-SEA mAbs. These mAbs
      appeared to recognize glycosidic residues, as suggested by 1) the inhibition of
      their reactivity by periodate oxidation of SEA, 2) the multiple polypeptide
      recognition in radioimmunoprecipitation and immunoblot assays and 3) reactivity
      with KLH. Anti-SEA mAbs were able to mediate in vitro killing of schistosomula
      but they were not consistently able to mediate passive transfer immunity in vivo.
      Three of anti-SEA mAbs were suitable for the performance of a sandwich ELISA for
      antibody detection in S. mansoni infected patients, allowing an increase in the
      signal to noise ratio as compared to the direct ELISA SEA method. Three anti-BE
      mAbs showed a more stage restricted pattern of antigen recognition by IIFA. Only
      one out of three seemed to be directed against glycan residues, but the other
      mAbs showed a plural pattern of polypeptide recognition on BE immunoblot,
      suggesting that repeated epitopic motifs are also present in different proteins
      within the same parasite developmental stage.

PMID- 7510900
TI  - [Autotransplantation in acute leukemia using totipotent cells mobilized with
      filgrastim].

PMID- 7510904
TI  - Frogs and toads in deserts.

PMID- 7510905
TI  - Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule.
AB  - Fas is an apoptosis-signaling receptor molecule on the surface of a number of
      cell types. Molecular cloning and nucleotide sequence analysis revealed a human
      Fas messenger RNA variant capable of encoding a soluble Fas molecule lacking the
      transmembrane domain because of the deletion of an exon encoding this region. The
      expression of soluble Fas was confirmed by flow cytometry and immunocytochemical
      analysis. Supernatants from cells transfected with the variant messenger RNA
      blocked apoptosis induced by the antibody to Fas. Levels of soluble Fas were
      elevated in patients with systemic lupus erythematosus, and mice injected with
      soluble Fas displayed autoimmune features.

PMID- 7510906
TI  - Total pelvic exenteration with or without sacral resection in patients with
      recurrent colorectal cancer.
AB  - Pelvic recurrence from colorectal cancer produces significant morbidity.
      Radiation can help palliate the pain produced by this recurrence. Frequently
      patients with recurrent colorectal cancer will progress to a constant unrelenting
      pain and obstructive uropathy with sacral and bladder involvement. These patients
      can be candidates for an aggressive surgical resection with the hope of
      significant palliation and prolonged survival. From October 1988 to December
      1991, six patients had total pelvic exenteration at our institution. Of these six
      patients, two had en bloc sacral resection at levels S1-S2 and one at S2-S3. Two
      patients had residual disease at the time of primary surgery, and in the other
      four patients, recurrence occurred 7 to 48 months after primary resection. One
      patient died with disease at 7 months, and five patients are alive at 9, 25, 25,
      37, and 37 months since the pelvic resection; four have no evidence of disease.
      The present Karnofsky performance status is 80% or greater in all patients. There
      were no operative deaths. Of the five living patients, the survival from
      diagnosis of the primary lesion is 25 to 97 months. Total pelvic exenteration and
      abdomino-sacral exenteration can produce significant palliation and prolong
      survival in a selected group of patients with pelvic recurrence from colorectal
      cancer.

PMID- 7510907
TI  - Resection of primary hepatic malignant fibrous histiocytoma, fibrosarcoma, and
      leiomyosarcoma.
AB  - Four patients had resection for primary hepatic sarcoma: one with malignant
      fibrous histiocytoma (MFH), two with poorly differentiated fibrosarcoma, and one
      with leiomyosarcoma. Age ranged from 40 to 69 years. One patient had a cousin and
      a grandmother who had died of hepatic tumors. At presentation, all patients had
      pain; one had tumor rupture, and one had mental changes and hypoglycemia. None
      had hepatitis or cirrhosis. Results of laboratory evaluation were nonspecific,
      including normal carcinoembryonic antigen and alpha-fetoprotein levels. Computed
      tomography showed hypodense masses with enhancement. Angiography showed a
      hypervascular mass in three patients and an avascular mass in the patient with
      MFH. Despite large tumors (8 to 32 cm), portal and hepatic veins were not
      invaded. The pattern of vascularization and lack of venous invasion helps
      differentiate primary hepatic sarcomas from hepatocellular carcinoma, especially
      in noncirrhotic patients. All patients had extensive hepatic resections, with one
      operative death. Immunohistochemical stains of the tumors were positive for
      vimentin but negative for epithelial markers, differentiating these lesions from
      other hepatic tumors. The patient with MFH died with recurrence at 10 1/2 months.
      The patient with the ruptured fibrosarcoma had a second resection and
      chemotherapy, but died with recurrence at 3 years. The patient with the
      leiomyosarcoma had a second resection and was disease free at 4 years. Resection
      of primary hepatic sarcoma is warranted, with potential survival measured in
      years.

PMID- 7510908
TI  - [Researches on collagen diseases between 1992 to 1993].

PMID- 7510909
TI  - Aprotinin reduces clopidogrel-induced prolongation of the bleeding time in the
      rat.
AB  - High doses of aprotinin have been shown to reduce blood loss and blood
      transfusion requirements in patients undergoing open heart surgery and recent
      studies in animals have shown that aprotinin was able to reduce bleeding
      associated with rt-PA administration. Our study was designed to demonstrate an
      effect of aprotinin (Iniprol) on the prolongation of the bleeding time associated
      with the treatment with a potent analogue of ticlopidine: clopidogrel. Bleeding
      time was determined in rats by transection of the tip of the tail. 2 hours after
      a single oral administration, clopidogrel (5 mg/kg, p.o.), induced a 4-fold
      increase in the bleeding time. Aprotinin administered as a bolus iv injection
      followed by continuous infusion strongly reduced bleeding time prolongation
      associated with clopidogrel treatment. This effect was dose-related and reached a
      maximum (congruent to 50% inhibition--P < 0.001) at and above the total dose of
      40 U Ph Eur/kg (80,000 KIU/kg). After administration of a total dose of 60 U Ph
      Eur/kg (120,000 KIU/kg), aprotinin modified neither the antiaggregating effect of
      clopidogrel nor its antithrombotic activity, as determined in various
      experimental models. For this reason, aprotinin might constitute a useful
      antagonist of the haemorrhagic risk associated with interventional therapy under
      treatment with ticlopidine or clopidogrel.

PMID- 7510911
TI  - Three-year safety and efficacy data on the use of finasteride in the treatment of
      benign prostatic hyperplasia.
AB  - OBJECTIVE: To assess the long-term safety and efficacy of finasteride in the
      treatment of symptomatic benign prostatic hyperplasia in patients treated with
      finasteride 5 mg for thirty-six months. METHODS: Two large multicenter studies
      were used. Patients were randomly assigned to treatment with finasteride, 1 or 5
      mg, or placebo for twelve months. After completing twelve months of therapy,
      patients were invited to enter an open extension to the study in which all
      patients received finasteride 5 mg. Urinary symptoms, urinary flow rate, prostate
      volume, and serum concentrations of prostate-specific antigen and
      dihydrotestosterone were measured periodically during the study. RESULTS: After
      thirty-six months of treatment with finasteride 5 mg, prostate volume was reduced
      from baseline by approximately 27 percent, maximum urinary flow rate improved by
      approximately 2.3 mL/second, and symptom scores improved by 3.6 points. Forty-two
      percent of patients had a 30 percent or greater decrease in prostate volume, 40
      percent of patients showed an increase of 3 mL/second or more in maximum urinary
      flow rate, and 48 percent of patients experienced a 50 percent or greater
      improvement in symptom scores. Finasteride was well tolerated and there was no
      evidence of increased adverse experiences with increased duration of treatment.
      CONCLUSIONS: The excellent safety profile and sustained clinical efficacy, over
      thirty-six months, of daily treatment with finasteride 5 mg recommend finasteride
      as a low-risk medical option for the treatment of symptomatic benign prostatic
      hyperplasia.

PMID- 7510910
TI  - Distribution of chlordecone to liver plasma membranes and recovery from
      hepatobiliary dysfunction in rats.
AB  - Chlordecone (CD) impairs biliary excretion of organic anions (including
      phenolphthalein glucuronide (PG), imipramine polar metabolites, and taurocholate)
      without evidence of hepatocellular necrosis in rats. In this study we
      investigated the hypothesis that CD-induced hepatobiliary dysfunction is
      dependent on CD concentration in liver plasma membranes where it inhibits active
      transport in vitro. Rats were treated by gavage (0 or 60 mg CD/kg in corn oil) 24
      or 72 h prior to bile duct cannulation. Biliary excretion of PG, a marker of
      hepatic organic anion transport, and [14C]mannitol, a marker of passive
      transcellular permeability, was determined. Biliary excretion of PG decreased
      approximately 25% in rats 24 h after CD treatment, however rats recovered control
      PG excretion rates 72 h after CD treatment. Recovery of PG excretion occurred
      despite higher liver homogenate [14C]CD concentrations at 72 h than at 24 h after
      [14C]CD treatment. Biliary clearance of [14C]mannitol decreased both 24 h and 72
      h after treatment. Even though the amount of [14C]CD retained in the liver was
      greater at 72 h than at 24 h after treatment, the concentration of [14C]CD in
      isolated liver plasma membranes (LPM) was the same (3.5-3.9 nmol/mg protein) at
      both times. There was a significant reduction in 5'-nucleotidase activity of LPM
      at 24 h but not at 72 h after CD. This study demonstrated no correlation between
      recovery from CD-induced hepatobiliary dysfunction and whole liver accumulation.
      Altered subcellular [14C]CD distribution (reduced LPM-to-homogenate concentration
      ratio was coincident with recovery.

PMID- 7510913
TI  - Ultrasonic volume monitoring in patient with prostate cancer treated by external
      beam radiation therapy.
AB  - OBJECTIVE: To determine whether or not tumor volume estimates are useful in
      predicting and detecting disease progression following radiation therapy in
      patients being treated for adenocarcinoma of the prostate. METHODS: Compare
      preradiation therapy ultrasound determined volumetric analysis of the prostate
      gland, the hypoechoic tumor lesion, and prostate-specific antigen (PSA) values to
      sequential post-therapy determinations. RESULTS: The average percent volume
      reduction rates at three months postradiation therapy of the entire prostate
      gland and the hypoechoic tumor lesion were 18.1 and 60 percent, respectively. The
      serum PSA value at three months decreased by 69.3 percent. After the first three
      months, further reductions in all three parameters were minimal. The volume of
      the histologically confirmed cancer lesions in progressing patients decreased at
      a slower rate than that of nonprogressing patients during the initial six months
      of follow-up (p = 0.03). Among the 14 progressing patients, a new hypoechoic
      lesion (5 of which were biopsy-positive) developed in 7, and 7 had persistent
      lesions. An elevated PSA was observed in 10 of the progressors. CONCLUSIONS: The
      volume change of the hypoechoic lesion was sensitive in detecting disease
      progression and mirrored the change in PSA levels. The monitoring of hypoechoic
      lesion volume is useful both to predict and to detect disease progression
      following radiation therapy while volume change of the prostate gland was not
      sensitive for these purposes.

PMID- 7510912
TI  - Relationship between diurnal rhythm of serum testosterone and two prostatic
      markers (PSA and PAP) in untreated prostate cancer.
AB  - OBJECTIVE: To clarify the relation between diurnal rhythm of serum levels of
      testosterone and two prostatic markers, prostate-specific antigen (PSA) and
      prostatic acid phosphatase (PAP). METHODS: Blood was obtained every four hours
      during a thirty-two-hour period from fourteen men with untreated prostate cancer.
      RESULTS: Serum levels of PSA and PAP showed circadian rhythm in 4 and 5 patients,
      respectively. About half of the remaining patients, the highest or nearly highest
      peaks of serum levels of PSA or PAP were observed in the afternoon rather than
      the morning. In 3 patients, circadian rhythms were not observed in serum levels
      of PAP, but the fluctuation patterns were the same as those of testosterone and
      showed synchronous movement. In 7 patients, serum testosterone levels were
      followed by the same fluctuation pattern for either PSA or PAP after some time
      delay. Little change in serum levels of PSA was seen throughout the thirty-two
      hour period despite large fluctuations of testosterone and PAP levels in 5
      patients. CONCLUSIONS: Close relation between the fluctuation in serum levels of
      PSA and PAP, and that in serum levels of testosterone during diurnal periods
      could be considered. However, the relationship between serum testosterone levels
      and those of PSA and PAP was ambiguous because of both the difference in the time
      delay of PSA and PAP in relation to testosterone and the small fluctuation in PSA
      despite obvious fluctuations in testosterone and PAP in some cases.

PMID- 7510914
TI  - Undetectable prostate-specific antigen in aging men.
AB  - Undetectable prostate-specific antigen was found in three aging men despite the
      absence of any prostatic surgery or exogenous hormonal deprivation. Clinical and
      elementary hormonal workup revealed the presence of secondary hypogonadism. This
      finding confirms the hormonal dependency of this prostatic marker and may, in
      some cases, explain the discrepancy between prostatic volume and the value of
      serum prostate-specific antigen.

PMID- 7510915
TI  - Prostate-specific antigen decline after casodex withdrawal: evidence for an
      antiandrogen withdrawal syndrome.
AB  - OBJECTIVE: To evaluate the relationship between antiandrogen withdrawal and
      change in prostate-specific antigen (PSA) when the antiandrogen in question is
      other than flutamide. METHODS: Presented is a case of a patient in whom the
      antiandrogen casodex was discontinued after clinical progression despite combined
      androgen blockade. RESULTS: A transient decline in serum PSA was observed after
      casodex withdrawal. CONCLUSIONS: The relationship between antiandrogen withdrawal
      and a change in PSA may be a general phenomenon, not unique to flutamide.

PMID- 7510917
TI  - Chronotoxicological effect of methyl mercury in rat submandibular gland.
      Immunohistochemical changes of r-EGF, S-100 protein and keratin.
AB  - The effect of toxicity of methyl mercury was investigated in the submandibular
      gland (SMG) of adult male rats subjected to 12 h light dark cycle (6 a.m. to 6
      p.m. light/resting phase; 6 a.m. to 6 p.m. dark/active phase). Two groups of rats
      received a defined dose of methyl mercury hydroxide at seven different time
      points during the active (dark) and resting (light) phase over a 24 h period.
      After 10 d, the rats were killed at 9 a.m. and 9 p.m. in the resting and active
      phase, respectively. The immunohistochemical distribution pattern of epidermal
      growth factor (r-EGF), S-100 protein and K8.12 keratin were studied in granular
      convoluted tubules (GCT). Those rats which received injections during the active
      phase (6 p.m. to 6 a.m.), showed stronger reactivity for r-EGF; however, the
      reactivity for S-100 protein was unchanged. On the contrary, in both groups, GCT
      cells showed intense staining for K8.12 keratin. It is concluded that the
      detoxification mechanism of mercury appears to be dependent on the
      chronobiological oscillation pattern of the GCT and their substructures.

PMID- 7510916
TI  - Dose-response relationships for the induction of P450 2B by 1,4-bis[2-(3,5
      dichloropyridyloxy)]benzne (TCPOBOP) in rat and cultured rat hepatocytes.
AB  - 1. The dose-response relationships for hepatic CYP2B induction by 1,4-bis[2-(3,5
      dichloropyridyloxy)]benzene (TCPOBOP) were examined in the male F344/NCr rat.
      TCPOBOP, administered for 14 days at 0-1000 ppm in the diet, caused concentration
      dependent induction of hepatic CYP2B1 protein and RNA, and of CYP2B-mediated
      catalytic activities (benzyloxy- and pentoxyresorufin O-dealkylation, and
      testosterone 16 beta-hydroxylation). ED50 values for CYP2B induction were > or =
      300 ppm dietary TCPOBOP. The maximal inductions observed were 66-88% of those
      resulting from exposure of the rats to 500 ppm dietary phenobarbital. 2. The EC50
      values for hepatic CYP2B induction were 1.5-3.0 microM (based on serum TCPOBOP)
      and 15-20 mumol/kg liver. 3. The maximal inductions of isozymes of the CYP3A
      subfamily, of microsomal epoxide hydrolase, and of glutathione S-transferases
      Ya/Yc and Yb1/Yb2 in rats exposed to TCPOBOP were 58-74% of those resulting from
      exposure of the rats to 500 ppm dietary phenobarbital. 4. The ED50 value for
      induction of benzyloxyresorufin O-dealkylation in cultured rat hepatocytes by
      TCPOBOP was determined to be 0.93 microM. The maximal induction of this activity
      caused by TCPOBOP was 87% of the maximum increases caused by phenobarbital. 5.
      The results indicate that TCPOBOP is a highly effective phenobarbital-type
      inducer in the rat when administered in the diet for 2 weeks at 1000 ppm. When
      extent of induction is related to serum total xenobiotic level, TCPOBOP would
      appear to be at least as potent as, if not more potent than, phenobarbital in the
      rat.

PMID- 7510918
TI  - Cytochemistry of satellite nucleoli in human lymphocytes.
AB  - Satellite nucleoli of lymphocytes were studied to provide additional information
      on the cytochemistry of these nucleoli particularly with respect to the presence
      of rDNA and RNA polymerase I. According to the results of the in situ
      hybridization satellite nucleoli contain rDNA similarly as characteristic
      nucleoli. Immunostaining demonstrated that satellite nucleoli similarly as
      characteristic nucleoli possess RNA polymerase I in addition to proteins B23, C23
      and fibrillarin. RNA of satellite nucleoli was detected in satellite as well as
      in characteristic nucleoli with buffered toluidine or methylene blue. The
      cytochemical evidence and morphology of satellite nucleoli strongly supports the
      supposition that these nucleoli represent solitary small nucleoli containing
      nucleolus organizer regions which did not participate in the formation of
      characteristic nucleoli.

PMID- 7510919
TI  - Biochemical and histochemical studies of plasminogen activator of urokinase type
      (u-PA) activity. I. A simple rapid semiquantitative fluorescent method for its
      detection in the tear fluid.
AB  - A simple rapid fluorescent method for the detection of plasminogen activator
      activity of urokinase type (u-PA) in the tear fluid is described. Small filter
      paper punches were soaked in the substrate solution (Z-Gly-Gly-Arg
      trifluoromethylcoumarinyl-7-amide, 1 mg/1 ml) and aprotinin 100 micrograms/1 ml)
      dissolved in 0.1 M Tris-HCl buffer, pH 7.2 and dried. The dried punches were
      soaked with tears (by direct contact of the punch with the site where the
      activity should be assessed or by dropping of 3-5 microliters of tears collected
      by a glass micropipette). The punches were incubated in a thermostat (37 degrees
      C) together with punches containing a known u-PA activity (calibrated punches) in
      preheated (37 degrees C) Petri dishes. In 1 min intervals (during the first 15
      min) and in 5 min intervals thereafter the probes were exposed to UV light, and
      the time of the first appearance of a bright yellow fluorescence was recorded. In
      punches containing 5 IU u-PA activity fluorescence appeared after 2 min
      incubation; 2.5 IU were detected after 5 min, 1.25 IU after 15 min, 0.625 IU
      after 30 min, 0.313 IU after 60 min, 0.156 IU after 90 min, and 0.078 IU after
      120 min incubation. This simple method is recommended for use particularly in
      clinical laboratories. It enables e.g. to obtain a rather quick information about
      the urokinase activity in the tear fluid and to start the treatment with an
      appropriate inhibitor, if necessary.

PMID- 7510920
TI  - The complexity of dopamine receptors and psychopharmacotherapy in children.
AB  - The efficacy of dopaminergic antagonists, which are neuroleptics, has been shown
      in children in varied clinical situations. Five dopaminergic receptors (D1, D2,
      D3, D4, D5) have thus far been cloned: their existence has thus been confirmed,
      but their functional significance remains to be determined. This publication
      reviews their main characteristics. The multiplicity of cerebral dopamine
      receptors is consistent with the future development of new, more selective and
      discriminating psychotropic drugs. The diversity of interactions of dopaminergic
      receptors, among themselves and with receptors for other neurotransmitters,
      however, explains the difficulty in understanding the mechanism of action of
      neuroleptics and defining their more rational use in children.

PMID- 7510921
TI  - Influences of stimulation frequency and temperature on interval-force
      relationships in guinea-pig papillary muscles.
AB  - Relationships between contractile force and the preceding and pre-preceding
      stimulation intervals were studied in papillary muscles by interposing variable
      test intervals during steady-state pacing. The strength of test contractions
      increased exponentially to a maximum as the preceding (test) interval was
      lengthened. Contractility decreased as an exponential function of pre-preceding
      interval. At 37 degrees C, the half times for these processes were unaffected by
      increasing the steady-state frequency from 1 to 3 Hz. At 27 degrees C, the force
      increase with preceding interval was accelerated and the decay with pre-preceding
      interval was retarded as the stimulation frequency was increased from 0.33 to 2
      Hz. The time-courses of force increase and decay were similar to each other
      during stimulation at an optimum frequency characteristic for the temperature.
      Cooling from 37 to 27 degrees C prolonged the half times for force increase and
      decay by factors of 4.5 and 3 respectively. The slope of the linear relationship
      between the force of the contraction pre-preceded by the test interval and the
      immediately subsequent contraction (recirculation fraction) was also halved.
      These results suggest that high stimulation frequency and low temperature
      uncouples cellular processes underlying the interval dependence of cardiac
      contractility. The temperature sensitivities are consistent with these processes
      being enzymatic. The reduced recirculation fraction provides a mechanism for the
      lowered threshold frequency for sustained mechanical alternans at 27 degrees C.

PMID- 7510923
TI  - Differences in vimentin distribution in glial cells in culture revealed with an
      antibody against a phosphorylated epitope.
AB  - We have previously described that spatial and temporal changes in the
      organization of vimentin that are correlated with protein kinase C (PKC)-induced
      phosphorylation of vimentin can be detected with the mouse monoclonal antibody B3
      in cultures of amoeboid microglia [Ciesielski-Treska et al. (1991) J. Neurosci.
      Res. 29, 362-378]. The antibodies were generated to native form of vimentin
      containing filaments and antibody B3 reveals a restricted immunostaining of
      vimentin in glial cells from human, rat and mouse origin. In the present study we
      show the distribution of epitope B3 analyzed by immunofluorescence within defined
      populations of rat glial cells. Relatively high immunoreactivity was found in
      Type 1 astrocytes, Type 2 astrocytes and oligodendrocytes had low
      immunoreactivity. Although the results suggested that in Type 1 astrocytes the
      phosphorylated epitope is prominent, its phosphorylation was not found to be cell
      cycle-dependent, and appeared unrelated to the organizational changes of
      intermediate filaments associated with the morphological conversion of polygonal
      to stellate astrocytes. As expected, the immunofluorescence was increased by
      exposition of astrocyte cultures to an activator of PKC, confirming our previous
      conclusion that the immunoreactivity of the epitope B3 depends on PKC-mediated
      phosphorylation. In addition, the finding that the immunofluorescence of vimentin
      was more homogeneous in quiescent, serum-deprived astrocytes and also in
      astrocytes exposed to an inhibitor of protein synthesis, cycloheximide, may
      suggest that phosphorylation of the epitope B3 depends on a protein factor
      present in fetal calf serum. The immunofluorescence studies on cultures enriched
      in Type 2 astrocytes and in oligodendrocytes indicate that the epitope B3 is
      hypophosphorylated in glial cells of this lineage and becomes dephosphorylated
      after terminal differentiation of oligodendrocytes. These observations suggest
      that in Type 2 astrocytes and in oligodendrocytes the low level of
      phosphorylation of vimentin could be related to the down regulation in vimentin
      expression.

PMID- 7510924
TI  - Nuclear patterns of apoptotic and developing neurons of superior cervical
      ganglion of newborn rat.
AB  - Superior cervical ganglion (SCG) neurons of female rats aged 3, 5 and 7 days
      revealed conspicuous nuclear changes in neurons undergoing postnatal cell death.
      Several qualitative and quantitative data such as nuclear size and shape, the
      presence of atypical chromocenters and chromatin textural features discriminated
      well neurons candidate to degeneration and those advancing in the direction of
      adult maturation. At least on morphological grounds, postnatal death of SCG
      neurons appears to be of apoptotic type. The sequence of nuclear events observed
      enables the recognition of the early stages of involution which prelude neuron
      degeneration.

PMID- 7510922
TI  - Changes in slow axonal transport of tubulin induced by local application of
      colchicine to rabbit vagus nerve.
AB  - The biochemical and morphological responses of the rabbit vagus nerve to local
      application of colchicine and to nerve crush were investigated. Fourteen days
      after the cervical vagus nerve had been crushed or subjected to local application
      of colchicine for 2 h, nodose ganglia of anaesthetized rabbits were either
      injected with [35S]methionine or [3H]leucine for studies of slow and fast axonal
      transport, respectively, or prepared for light microscopical examination. The
      radio-labelled proteins of the faster of the two slow transport groups (SCb; 25
      30 mm day-1) were separated by one- or two-dimensional polyacrylamide gel
      electrophoresis and both radio-labelled tubulin and actin were quantified by
      densitometry from resulting fluorographs of gels. A relative increase in radio
      labelled tubulin was found in SCb in the crushed and colchicine-treated nerves;
      this increase persisted for up to 50 days after nerve crush. Morphological
      changes in nerve cell bodies induced by colchicine were similar, but smaller in
      magnitude than those in crushed nerves. It is concluded that a temporary arrest
      of axonal transport produced by colchicine can lead to a redistribution of
      tubulin transport comparable with that found in regenerating nerve.

PMID- 7510925
TI  - Recurrent pancreatitis after treatment with hydrochlorothiazide.

PMID- 7510926
TI  - The applicability of a keratin 7 monoclonal antibody in routinely Papanicolaou
      stained cytologic specimens for the differential diagnosis of carcinomas.
AB  - The monoclonal antibody OV-TL 12/30, which detects keratin 7, was tested for its
      usefulness in cytologic diagnosis by reincubating previously Papanicolaou-stained
      slides. For this purpose malignant effusions of 73 patients with histologically
      confirmed cancers of the colon, ovary, mesothelium, breast, lung, esophagus,
      pancreas, urinary bladder, stomach, kidney, and prostate were used. All malignant
      cells from ovarian adenocarcinomas were positive, whereas malignant cells from
      colonic adenocarcinomas and malignant mesotheliomas were negative.
      Adenocarcinomas of gastric, renal, pancreatic, esophageal, and mammary origin
      demonstrated variable staining. Transitional cell carcinomas were positive,
      whereas squamous and small cell lung carcinomas were negative. Because OV-TL
      12/30 does not react with normal and atypical mesothelial cells in these
      preparations, this reagent is a valuable tool in distinguishing benign
      mesothelial cells and adenocarcinoma cells. The authors' results demonstrate that
      this antibody is an excellent tool in the differential diagnosis of malignant
      cells in effusions and can be used in routinely stained cytologic specimens to
      determine primary tumor localization. In addition to its ability to distinguish
      between ovarian and colonic adenocarcinomas, its negativity in mesotheliomas may
      prove helpful in several diagnostic considerations.

PMID- 7510928
TI  - Application of new technology to the detection, identification, and antimicrobial
      susceptibility testing of mycobacteria.
AB  - Mycobacteria are reemerging as important causes of human disease. The increase in
      mycobacterial infections has prompted the development of more rapid and efficient
      ways of detecting and characterizing mycobacteria in the clinical microbiology
      laboratory. Methods currently in use or under development include more sensitive
      methods of direct detection, improved techniques for culture, identification, and
      susceptibility testing, and the use of nucleic acid probes for identification and
      epidemiologic typing. Broad application of rapid and sensitive methods for
      detection and characterization of mycobacteria are essential if we are to limit
      the spread of Mycobacterium tuberculosis (TB) and provide optimal care for
      patients infected with TB or other Mycobacterium species.

PMID- 7510927
TI  - Expression of CD24 (BA-1) predicts monocytic lineage in acute myeloid leukemia.
AB  - Fifty-seven cases of acute myeloid leukemia (AML), which had been subtyped by
      French-American-British morphologic and cytochemical criteria as myeloid (M1, M2)
      or monocytic (M4, M5), were retrieved from the files of the Division of
      Hematopathology, University of Iowa. Corresponding immunophenotyping data were
      reviewed with attention to the expression of CD14 (MY4) and CD24 (BA-1). Of 20
      cases expressing CD24, 19 were M4 or M5, whereas all 14 cases expressing CD14
      were of monocyte lineage. Therefore, CD14 was a highly specific (100%) but only
      moderately sensitive (58%) marker for distinguishing classes M1 or M2 from M4 or
      M5. By contrast and unexpectedly, CD24 was nearly as specific (97%), but more
      sensitive (79%) in marking M4 or M5 cells. This appears to be true even though
      CD24 is apparently not expressed on normal monocytes. When positive staining for
      either or both antibodies (CD24 or CD14) was considered indicative of a monocytic
      leukemia, the sensitivity of immunophenotyping in distinguishing M4/M5 from M1/M2
      AML rose to 92%, while maintaining 97% specificity. The authors discuss a recent
      observation that may help explain the unexpected expression of CD24 in monocytic
      AML. They conclude that the usefulness of CD24 in identifying monocytic AML may
      exceed that of CD14, and that the use of CD24 and CD14 in combination improves
      the ability of flow cytometry to distinguish myeloid from monocytic acute
      leukemias.

PMID- 7510930
TI  - Terazosin now indicated for benign prostatic hyperplasia.

PMID- 7510929
TI  - New technique for measuring tacrolimus concentrations in blood.

PMID- 7510931
TI  - Prenatal detection of epidermolysis bullosa letalis with pyloric atresia in a
      fetus by abnormal ultrasound and elevated alpha-fetoprotein.
AB  - We report on the prenatal diagnosis of epidermolysis bullosa letalis with pyloric
      atresia in a pregnancy not known to be at risk for this condition. Elevated
      maternal serum alpha-fetoprotein levels led to ultrasonography which demonstrated
      gastric dilatation, consistent with pyloric atresia, and echogenic particles in
      the amniotic fluid, the "snowflake sign," previously described in two pregnancies
      of fetuses with disorders of skin sloughing. Amniotic fluid alpha-fetoprotein was
      markedly elevated and the acetylcholinesterase was positive. The diagnosis of
      epidermolysis bullosa letalis with pyloric atresia was confirmed after delivery
      by electron microscopy of fetal skin which showed typical changes of hypoplastic
      absent hemidesmosomes and separation along the dermal-epidermal junction. None of
      these abnormal prenatal findings are consistently present in pregnancies with
      epidermolysis bullosa with pyloric atresia. Thus, although useful when abnormal,
      when the test results are normal, the need for confirmatory fetoscopy and fetal
      skin biopsy remains.

PMID- 7510932
TI  - Duchenne/Becker muscular dystrophy carrier detection using quantitative PCR and
      fluorescence-based strategies.
AB  - Dystrophin gene deletions account for up to 68% of all Duchenne (DMD) and Becker
      (BMD) muscular dystrophy mutations. In affected males, these deletions can be
      detected easily using multiplex PCR tests which monitor for exon presence. In
      addition, quantitative dosage screening can discriminate female carriers. We
      previously analyzed multiplex PCR products by gel electrophoresis and
      quantitation of fluorescently labeled primers with the Gene Scanner in order to
      test carrier status. These multiplex PCR protocols detect DMD gene deletions
      adequately, but require up to 18 pairs of fluorochrome-labeled primers. We
      previously described two alternative fluorescent labeling strategies, each with
      approximately 1,000-fold greater sensitivity than ethidium bromide staining,
      which can be used to quantify the products of multiplex PCR. The first method
      uses the DNA intercalating thiazole orange dye TOTO-1 to stain PCR products after
      20 cycles. In the second method, fluorescein-12,2'-dUTP is incorporated into
      products during PCR as a fluorescent tag for subsequent quantitative dosage
      studies. Both methods label all multiplexed exons including the 506 bp exon 48
      fragment that is difficult to detect and quantify by standard ethidium bromide
      staining. Using this approach, we determined DMD/BMD carrier status in 24
      unrelated families using a fluorescent fragment analyzer. Analysis of
      fluorochrome-labeled PCR products facilitates quantitative multiplex PCR for gene
      dosage analysis.

PMID- 7510934
TI  - Necrotizing epiglottitis in a patient with procainamide-induced neutropenia.

PMID- 7510935
TI  - Peptide map analysis of recombinant human granulocyte colony stimulating factor:
      elimination of methionine modification and nonspecific cleavages.
AB  - Procedures for HPLC peptide map analysis of recombinant human granulocyte colony
      stimulating factor include reduction and S-carboxymethylation of the denatured
      protein, as well as protease digestion with Staphylococcus aureus endoproteinase
      Glu-C followed by reverse-phase liquid chromatographic separations. Under
      nonoptimized experimental conditions analytical problems including methionine
      modification during carboxymethylation, as well as generation of large, insoluble
      fragments and nonspecific cleavages during proteolytic digestion, occurred. These
      problems have complicated the analysis of peptide digests and affected the
      performance of HPLC columns. This report describes the elimination of these
      problems by optimizing peptide mapping procedures. We found that mild reduction
      and alkylation conditions can prevent methionine modification, while protease
      digestion in the presence of urea at room temperature alleviates generation of
      peptides derived from incomplete digestion and nonspecific cleavage by
      endoproteinase Glu-C. Peptide maps generated using the optimized procedures
      contain fewer peptide peaks with higher recovery. Elimination of incomplete
      digestion, which generates fewer larger, insoluble peptides, substantially
      extends the life of reverse-phase columns. The optimized method reproducibly
      produced peptide maps suitable for routine analysis.

PMID- 7510936
TI  - Comparative spinal neuropathology of hydromorphone and morphine after 9- and 30
      day epidural administration in sheep.
AB  - Despite extensive clinical use of epidural morphine and to a lesser extent
      hydromorphone, the neurotoxicologic effects of large-dose epidural administration
      have not been reported. We compared the impact on behavior, blood and
      cerebrospinal fluid (CSF) chemistry and hematology, and neuropathology of both
      epidural morphine (M) and hydromorphone (H) versus preservative-free normal
      saline (S) given to control animals. Silicone lumbar epidural catheters were
      implanted in adult sheep and attached to either a subcutaneous port (acute 9-day
      study) or continuous flow type implantable drug pump (chronic 30-day study)
      through which the ewes were repeatedly exposed to either the epidural test drug
      or to similar volumes of saline. The 9-day groups received 5 mL of epidural
      injections twice daily with the dose incrementally increased as follows: M (n =
      6) 40 mg/d, 4 mg/mL; H (n = 6), 16 mg/d, 1.6 mg/mL; S (n = 3), preservative-free
      normal saline. The 30-day M and H groups were continuously infused epidurally
      with increasing concentrations eventually augmented with daily epidural boluses:
      M group (n = 3), 100 mg maximum daily dose, 25 mg/mL maximum concentration; H
      group (n = 3), 30 mg maximum daily dose, 10 mg/mL maximum concentration; S group
      (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7510933
TI  - Rett syndrome associated with tuberous sclerosis in a male and in a female:
      evidence for arrested motor and mental development.
AB  - Two sporadic cases of tuberous sclerosis presented with flexion spasms in a male
      and early intractable seizures evolving into a Lennox-Gastaut syndrome in a
      female. Early hypotonia and lack of substantial motor development are key
      features of the Rett syndrome, more easily overlooked than hand-wringing. Clumsy
      self-feeding and immature ambulation were the highest achievements in the second
      case now aged 36 years. Immaturity rather than degeneration, dementia, or assumed
      tissue destruction, is the capital feature of many disorders of early brain
      development leading to profound motor as well as mental retardation. Studying
      unusual clinical combinations is more likely to shed light on the underlying
      etiology than focusing on procrustean syndrome definitions.

PMID- 7510937
TI  - Rheologic effects of plasma substitutes used for preoperative hemodilution.
AB  - This study was designed to compare the influence of various plasma substitutes,
      administered for preoperative hemodilution, on blood rheology. We studied 40
      patients, ASA grade I, who underwent elective facial reconstructive surgery and
      received 4% albumin (n = 10), 3.5% dextran 40 (n = 10), gelatin (n = 10), or
      hydroxyethyl starch (HES) (n = 10). Ten patients, undergoing the same surgical
      procedure without hemodilution, were chosen as controls. After hemodilution,
      hematocrit was decreased approximately 30%. Fibrinogen decreased in all tested
      groups except in the gelatin group. Plasma viscosity decreased with albumin (1.13
      +/- 0.05 to 1.06 +/- 0.03 mPa.s; P < 0.01) and increased with HES (1.15 +/- 0.04
      to 1.22 +/- 0.05 mPa.s; P < 0.01). At a high shear rate, the blood viscosity
      decreased in all groups. In contrast, at a low shear rate and at 40% corrected
      hematocrit, the blood viscosity decreased in the albumin (15.9 +/- 1.9 to 13.1 +/
      2.1 mPa.s; P < 0.01) and the dextran 40 (16.9 +/- 2.9 to 12.8 +/- 2.5 mPa.s; P <
      0.01) groups and was unchanged in the gelatin and the HES groups. Erythrocyte
      aggregation (measured with primary aggregation time) was markedly decreased in
      the albumin (3.27 +/- 1.74 to 7.03 +/- 2.95 s; P < 0.01) and in the dextran 40
      (2.72 +/- 0.58 to 6.24 +/- 2.55 s; P < 0.001) groups, unchanged with HES, and
      increased with gelatin (2.41 +/- 0.90 to 1.55 +/- 0.33 s). These findings suggest
      that albumin and dextran 40 may be the plasma substitutes of choice for
      preoperative hemodilution when this technique aims to improve rheologic
      conditions.

PMID- 7510938
TI  - Tumor-associated angiogenesis in prostate cancer.
AB  - All solid tumors require the induction of new blood vessels to grow. To begin to
      study this phenomenon in prostate cancer, we investigated the intensity of tumor
      associated angiogenesis in prostate non malignant and malignant tissue.
      Angiogenesis was measured by quantitating microvessels in a total of 67 patients:
      23 non malignant biopsy specimens, and 34 malignant specimens from patients who
      had undergone prostatectomy. Angiogenic activity in prostatic cancer
      (prostatectomy) tissue (utilizing Factor VIII staining) was then correlated with
      pathological staging (Whitmore-Jewitt). Overall there appeared to be a trend of
      increasing microvessel count (MVC) from benign through the advancing stages of
      prostate cancer. Based on mean microvessel counts we were able to distinguish
      stage D from all other pathological stages (p = 0.004 between stages C and D).
      There was, however, no statistically significant difference between stage B and
      C. We conclude that tumor associated angiogenesis in prostate cancer may have
      both clinical and pathological significance in prostate cancer.

PMID- 7510939
TI  - Frequency and location of mitoses in prostatic intraepithelial neoplasia (PIN).
AB  - The aim of our study was to assess the frequency and location of mitoses in
      routine haematoxylin- and eosin-stained sections of prostatic intraepithelial
      neoplasia (PIN) and then to compare the patterns with those in benign prostatic
      hyperplasia (BPH) and prostatic invasive adenocarcinoma (PAC). The frequency of
      mitoses in the epithelial cell layers increased from BPH through PIN up to PAC.
      The proportions of mitoses in PIN lesions of low grade (PINlow) and high grade
      (PINhigh) were greater than in BPH (mean 0.001%; standard error, SE, 0.001%), the
      values decreasing from the basal layer towards the lumenal. In PINlow, the mean
      category values were 0.087% (SE 0.04%) in the basal, 0.046% (SE 0.033%) in the
      intermediate and 0.024% (SE 0.024%) in the lumenal position. In PINhigh, the mean
      category values were 0.194% (SE 0.178%) in the basal position, 0.075% (SE 0.06%)
      in the intermediate and 0.049% (SE 0.033%) in the lumenal position. The
      proportions of mitoses in adenocarcinoma with cribriform pattern decreased from
      the basal towards the lumenal layer, as for PIN: 0.154% (SE 0.096%) in the basal
      position, 0.072% (SE 0.044%) in the intermediate and 0.064% (SE 0.04%) in the
      lumenal position. In the solid/trabecular adenocarcinomas, the mean category
      value in the cell layer adjacent to the stroma was 0.22% (SE 0.111%), whereas in
      the other cell layers it was 0.074% (SE 0.045). In small and large acinar
      adenocarcinomas, the proportions of mitoses were 0.058% (SE 0.024%) and 0.068%
      (SE 0.019%), respectively. In conclusion, the evaluation of mitotic frequency and
      location in haematoxylin- and eosin-stained sections gives accurate information
      on how the mitotic activity in PIN compares with BPH and PAC.

PMID- 7510940
TI  - Development and prevention of metastasis.
AB  - Metastatic spread of malignancy is the primary cause of treatment failure and
      subsequent death in cancer patients. All cancers have the capability to
      metastasize, however, there are notable exceptions which rarely if ever
      metastasize. These include basal cell carcinoma, or cancers which are primarily
      locally invasive such as primary brain cancers. Is metastasis is an earlier
      process in cancer progression than originally hypothesized? Over 70% of patients
      have occult or overt metastatic disease at the time of presentation. Thus, the
      overwhelming proportion of patients have disease which is not surgically
      resectable for cure at the time of diagnosis. Metastasis is a continuous process
      commencing early in the growth of the primary tumor before it is clinically
      detectable by the most sensitive of means. In addition, metastases have the
      propensity to metastasize. The size and age variation in metastases, their
      dispersed anatomic locations, the local vascular and lymphatic environment, and
      their heterogeneous composition hinder complete surgical extirpation of disease
      and limit the effective concentration of anticancer drugs that can be delivered
      to metastatic colonies.

PMID- 7510941
TI  - Phylogenetic analysis and development of probes for differentiating
      methylotrophic bacteria.
AB  - Fifteen small-subunit rRNAs from methylotrophic bacteria have been sequenced.
      Comparisons of these sequences with 22 previously published sequences further
      defined the phylogenetic relationships among these bacteria and illustrated the
      agreement between phylogeny and physiological characteristics of the bacteria.
      Phylogenetic trees were constructed with 16S rRNA sequences from methylotrophic
      bacteria and representative organisms from subdivisions within the class
      Proteobacteria on the basis of sequence similarities by using a weighted least
      mean-square difference method. The methylotrophs have been separated into
      coherent clusters in which bacteria shared physiological characteristics. The
      clusters distinguished bacteria which used either the ribulose monophosphate or
      serine pathway for carbon assimilation. In addition, methanotrophs and
      methylotrophs which do not utilize methane were found to form distinct clusters
      within these groups. Five new deoxyoligonucleotide probes were designed,
      synthesized, labelled with digoxigenin-11-ddUTP, and tested for the ability to
      hybridize to RNA extracted from the bacteria represented in the unique clusters
      and for the ability to detect RNAs purified from soils enriched for methanotrophs
      by exposure to a methane-air atmosphere for one month. The 16S rRNA purified from
      soil hybridized to the probe which was complementary to sequences present in 16S
      rRNA from serine pathway methanotrophs and hybridized to a lesser extent with a
      probe complementary to sequences in 16S rRNAs of ribulose monophosphate pathway
      methanotrophs. The nonradioactive detection system used performed reliably at
      amounts of RNA from pure cultures as small as 10 ng.

PMID- 7510942
TI  - Detection of alcohol-tolerant hiochi bacteria by PCR.
AB  - We report a sensitive and rapid method for detection of hiochi bacteria by PCR.
      This method involves the electrophoresis of amplified DNA. Nucleotide sequences
      of the spacer region between 16S and 23S rRNA genes of 11 Lactobacillus strains
      were identified by analysis of PCR products. Five primers were designed by
      analysis of similarities among these sequences. A single cell of Lactobacillus
      casei subsp. casei could be detected when purified genomic DNA was used as the
      template. When various cell concentrations of L. casei subsp. casei were added to
      50 ml of pasteurized sake and the cells were recovered, the detection limit was
      about one cell. No discrete band was observed in electrophoresis after PCR when
      human, Escherichia coli, mycoplasma, Acholeplasma, yeast, or mold DNA was used as
      the template.

PMID- 7510943
TI  - Rapid detection and identification of Vibrio anguillarum by using a specific
      oligonucleotide probe complementary to 16S rRNA.
AB  - Partial 16S rDNA from Vibrio collection type strains and recent isolates of
      Vibrio-related strains were sequenced and compared with previously published
      sequences. A 24-base DNA oligonucleotide (VaV3) was designed and used as a
      specific probe for detection and identification of Vibrio anguillarum. Its
      specificity was tested against collection type strains and environmental isolates
      and no cross-reaction was found. The probe detected 8 of the 10 V. anguillarum
      serovars. It was applied to screen different Vibrio-related strains isolated from
      marine hatcheries and fish farms. The detection limit in DNA-DNA slot blot
      hybridization was 150 pg.

PMID- 7510944
TI  - 3,5,8-Trihydroxy-4-quinolone, a novel natural inhibitor of the reverse
      transcriptases of human immunodeficiency viruses type 1 and type 2.
AB  - The natural product of the Red Sea sponge Verongia sp., identified as 3,5,8
      trihydroxy-4-quinolone, was found to be a potent inhibitor of the RNA-directed
      DNA synthesis of the reverse transcriptases (RTs) of human immunodeficiency
      viruses type 1 and type 2 (HIV-1 and HIV-2, respectively). This inhibition was
      unaffected by the nature of the primer template used for DNA synthesis. The DNA
      dependent DNA polymerase activity was inhibited to a lesser extent, whereas the
      ribonuclease H (RNase H) function associated with both HIV RTs was only slightly
      inhibited. The inhibition by the trihydroxyquinolone is reversible and
      noncompetitive with respect to both substrates--dTTP and the template primer
      poly(rA)n.oligo(dT)12-18. The inhibitor binds HIV-1 RT with a high affinity (Ki =
      0.46 microM). This compound was shown also to inhibit the catalytic activities of
      the RT of murine leukemia virus, establishing the general inhibitory effect on
      retroviral RTs. Introductions of acetyl or methoxy moieties at positions with
      potential activity have generated three synthetic analogs of the natural
      compound. Only one analog, 5,8-dimethoxy-4-quinolone, exhibited an inhibition
      potency similar to that of the unmodified compound. Analysis of the three analogs
      has led us to the conclusion that the hydroxyl group at the ortho position to the
      carbonyl group in the pyridinone ring is a key structural element for the
      inhibitory activity. Thus, it could well be that the inhibitor interacts with the
      enzyme through a hydrogen bond of this hydroxyl group. We hope that the
      identification of the inhibitory site of the compound might be an important step
      toward the rational design of new potent anti-HIV RT drugs.

PMID- 7510945
TI  - Developmental setback in severe visual impairment.
AB  - Developmental setback in children initially thought to be of normal cognitive
      potential is a serious complication of severe visual impairment; the prevalence,
      diagnostic specificity, clinical presentation, and factors that contribute to its
      genesis require systematic investigation. The findings are reported of a
      retrospective case review over a 15 year period of children attending the
      developmental vision clinic at the Wolfson Centre of the Institute of Child
      Health. One hundred and two children met the inclusion criteria of a period of
      normal development confirmed at initial assessment when aged less than 16 months,
      absence of additional disabilities, and follow up to at least 2.5 years of age.
      Developmental setback in their second or third year occurred in 10 (31%) of 32
      children who were totally blind throughout (minimal perception of light or less),
      one (4%) of 25 who, though blind at first assessment, showed visual improvement,
      and none of 49 children with better vision throughout (awareness for near, large
      objects). This represents a significantly greater risk for totally blind children
      than for the other groups. The course and characteristics of the affected
      children varied, but all had visual diagnoses involving the nervous elements of
      the visual system, and 60% had major social adversity factors. The role of
      primary maldevelopment of the central nervous system, the degree of visual
      impairment, the developmental and emotional climate, and the stage of attentional
      and behavioural development in the causation of adverse developmental outcome are
      discussed.

PMID- 7510946
TI  - Analysis of cribriform morphology in prostatic neoplasia using antibody to high
      molecular-weight cytokeratins.
AB  - Histologic review of 48 radical prostatectomy specimens containing both prostatic
      adenocarcinoma (PC) and high-grade prostatic intraepithelial neoplasia (PIN)
      resulted in 23 cases containing neoplastic cribriform gland (CGs) at the
      periphery or within PC fields. The histologic characteristics of CG PIN mimic
      those of CG PC in that a discernible basal cell layer defines CG PIN, while CG PC
      lacks a basal layer. To detect the presence of basal cells in CGs, step sections
      were immunostained with monoclonal antibody 34 beta E12 to high-molecular-weight
      cytokeratins (HMCK) found in basal cells, but not in PC cells. Optimal staining
      of formalin-fixed sections required pepsin predigestion followed by 14-hour
      monoclonal antibody incubation at 4 degrees C. Of 436 CG foci identified, 239
      (55%) were outlined by a circumferential HMCK-positive layer (identifying PIN);
      182 (42%) totally lacked this layer (identifying PC), with appropriate internal
      controls; and 15 (3%) stained indeterminately. In an attempt to distinguish CG
      PIN from PC by routine histologic examination alone, CGs with open, round spaces
      were classified as classic (156 foci); nonclassic CGs (265 foci) featured
      irregular oblong to slitlike spaces. Cribriform gland PIN defined by HMCK
      outlining was more often nonclassic (193 CG foci) in histologic pattern, and CG
      PC was usually "classic" (110 CG foci) (chi 2 = 75; P < .001). We conclude that
      (1) more than half (55%) of the CGs in the PC tumors studied contain a basal cell
      layer fulfilling the definition of PIN; (2) focal and isolated HMCK positivity is
      found amid PC, and thus the overall pattern of staining together with
      morphological features is critical to correctly exclude carcinoma; (3) grading of
      PC on the basis of the presence of CGs may lead to erroneous results if PIN foci
      are misinterpreted as PC; and (4) since CG PIN is usually found in intimate
      anatomic association with PC, HMCK staining to detect basal cells in isolated CGs
      encountered in biopsy specimens may be a useful diagnostic discriminant.

PMID- 7510947
TI  - A single clonal origin of neoplastic B cells in a patient with CD5+B-intermediate
      lymphocytic lymphoma terminating in plasmacytoid differentiation.
AB  - To investigate the clonal origin of a case of CD5+B-intermediate lymphocytic
      lymphoma terminating in plasmacytoid differentiation, we analyzed the
      immunophenotype and immunoglobulin gene rearrangements in the first and second
      lymph nodes from which biopsy specimens were taken. Immunohistochemical study
      revealed that both neoplasms have the same immunoglobulin light chain type (kappa
      light chain). Immunoglobulin gene analysis using the Southern blot method
      revealed the identical immunoglobulin heavy chain and kappa-light chain gene
      rearrangements in both neoplasms. These findings suggest that both neoplasms are
      derived from a single clonal B cell. The present case may help a further
      understanding of CD5+B-lymphocyte differentiation pathway.

PMID- 7510948
TI  - The application of immunotargeting into cancer chemotherapy with carboplatin: in
      vitro and in vivo studies.
AB  - Anti-tumor effects of the following 2 cis-diammin (1, 1-cyclobutandicarboxylato)
      platin II (carboplatin, Bristol-Myers-Squibb) conjugates were evaluated through
      both in vitro and in vivo experiments: (1) carboplatin coupled with anti
      cytokeratin monoclonal antibody (MAb), TS1 via carboxymethyl dextran (carboplatin
      carboxymethyl dextran-TS1), and (2) carboplatin-carboxymethyl dextran-avidin
      targeted to biotinylated TS1. Using 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide
      and N-hydroxysuccinimide, carboplatin was conjugated to carboxymethyl dextran,
      TS1, or avidin, at high molar ratios. The staining positivity of carboplatin
      carboxymethyl dextran-TS1 in indirect immunofluorescence was almost identical to
      that of the original MAb. The average dose of carboplatin given in each treatment
      was about 60% of a clinical dose. Regarding cytotoxicity, the free drug showed
      the strongest effect and the best dose-dependency in cell lines: HeLa and ZR-75
      1. An in vivo study giving carboplatin-MAb conjugates or free drug to HeLa tumor
      bearing nude rats proved that the efficacy of carboplatin-carboxymethyl dextran
      TS1 in HeLa tumor was not greater than that of the free carboplatin.

PMID- 7510949
TI  - Receptors for gut regulatory peptides.
AB  - Receptors for regulatory peptides (hormones or neurotransmitters) play a pivotal
      role in the ability of cells to taste the rich neuroendocrine environment of the
      gut. Recognition of low concentration of peptides with a high specificity and
      translation of the peptide-receptor interaction into a biological response
      through different signalling pathways (adenylyl cyclase-cAMP or phospholipase C
      phosphatidylinositol) are crucial properties of receptors. While many new
      receptors have been identified and thereafter characterized functionally during
      the 1980s, molecular biology now emerges as the privileged way for the structural
      characterization and discovery of receptors. Different strategies of receptor
      cloning have been developed which may or may not require prior receptor
      purification. Among cloning strategies that do not require receptor purification,
      homology screening of cDNA libraries, expression of receptor cDNA or mRNA in
      Xenopus laevis oocytes or in COS cells, and the polymerase chain reaction method
      achieved great success, e.g. cloning of receptors for cholecystokinin, gastrin,
      glucagon-like peptide 1, gastrin-releasing peptide/bombesin, neuromedin K,
      neuropeptide Y, neurotensin, opioids, secretin, somatostatin, substance K,
      substance P and vasoactive intestinal peptide. All these receptors belong to the
      superfamily of G-protein-coupled receptors which consist of a single polypeptide
      chain (350-450 amino acids) with seven transmembrane segments, an N-terminal
      extracellular domain and a C-terminal cytoplasmic domain. In this chapter, we
      have detailed the properties of three receptors which play an important role in
      digestive tract physiology and illustrate various signal transduction pathways:
      pancreatic beta-cell galanin receptors which mediate inhibition of insulin
      release and intestinal epithelial receptors for vasoactive intestinal peptide and
      peptide YY, which mediate the stimulation and inhibition of water and electrolyte
      secretion, respectively.

PMID- 7510952
TI  - Efficient encapsulation of proteins within liposomes for slow release in vivo.
AB  - A highly efficient method for the liposome encapsulation of granulocyte colony
      stimulating factor (rhG-CSF) was developed. The method was found to be gentle and
      led to no protein aggregation, denaturation or loss of protein activity. The
      liposomes obtained were judged to be oligolamellar based on a comparison of the
      actual with the theoretical trapped volumes. Slow release of encapsulated
      material from the liposomes was demonstrated both in vitro (90% serum, 37 degrees
      C) and in vivo after subcutaneous injection.

PMID- 7510950
TI  - Nitric oxide synthases in mammals.

PMID- 7510951
TI  - Identification of a keratin-associated protein that localizes to a membrane
      compartment.
AB  - We describe the characterization of an acidic glycoprotein (molecular mass
      approximately 85 kDa) that associates with keratin intermediate filaments of
      'simple'-type epithelia. Using a number of anti-keratin monoclonal antibodies,
      the 85 kDa glycoprotein was identified by co-immunoprecipitation with keratin
      polypeptides 8 and 18 (K8/18) from the human colonic epithelial cell line HT29
      and several other epithelial cell lines. This Keratin-Associated Protein (termed
      KAP85) was readily detected after in vitro galactosylation of K8/18
      immunoprecipitates obtained from mitosis-arrested cells. Its solubilization and
      detection were dependent on the detergent used, and it was barely detected after
      in vitro galactosylation of asynchronously growing G0/G1-phase cells. Its poor in
      vitro galactosylation in G0/G1-phase cells is likely a reflection of the lack of
      available terminal N-acetylglucosamine residues, since it can be labelled to a
      similar extent in G0/G1- and G2/M-phase cells using NaIO4/NaB3H4. Glycosidase
      digestion showed that KAP85 contains high mannose and complex oligosaccharides.
      Fractionation of total cellular K8/18 into soluble and cytoskeletal insoluble
      pools showed that KAP85 associates exclusively with the cytoskeletal K8/18 pool.
      Subcellular fractionation showed that KAP85 co-localizes with a plasma-membrane
      enriched fraction that includes the transferrin receptor and KS-1 antigen. Our
      results demonstrate in vitro evidence of a membrane-associated glycoprotein
      (KAP85) which may serve as an attachment site for filamentous K8/18.

PMID- 7510954
TI  - Nitric oxide production depends on preceding tetrahydrobiopterin synthesis by
      endothelial cells: selective suppression of induced nitric oxide production by
      sepiapterin reductase inhibitors.
AB  - Using murine vascular endothelial cells expressing both constitutive and
      inducible nitric oxide synthases (cNOS and iNOS), we explored the feasibility of
      suppressing cytokine-induced nitric oxide (NO) production without affecting
      constitutive NO production by inhibition of the tetrahydrobiopterin (BH4)
      biosynthesis. We show in this study that in endothelial cells cytokine/endotoxin
      activated BH4 synthesis precedes the induction of NO generation. Using the
      sepiapterin reductase inhibitors phenprocoumon or dicumarol as BH4 synthesis
      inhibitors, we achieved a pronounced and selective suppression of induced NO
      production in cytokine-activated endothelial cells. Addition of exogenous BH4,
      but not sepiapterin, restored NO production in the presence of the inhibitors.
      Despite profound inhibition of the BH4 biosynthesis, constitutive NO synthesis
      was not affected, thereby demonstrating the selectivity and specificity of the
      inhibitors. Suppression of enhanced NO production by sepiapterin reductase
      inhibitors such as cumaroles could provide pharmacologic means for therapeutic
      interventions in NO-mediated pathophysiologic events.

PMID- 7510953
TI  - The role of a phosphatidylcholine-specific phospholipase C in the production of
      diacylglycerol for nitric oxide synthesis in macrophages activated by IFN-gamma
      and LPS.
AB  - Murine macrophages activated by interferon (IFN)-gamma and bacterial
      lipopolysaccharide (LPS) produce large amounts of nitric oxide (NO), which is a
      critical mediator for a variety of biological functions. The expression of this
      inducible NO synthase (iNOS) involves a protein kinase C (PKC)-dependent pathway,
      but the mechanism for the PKC activation in this system is unclear. Through
      analysis of diacylglycerol (DAG) synthesis and choline metabolism in activated
      macrophages, direct evidence is provided that NO synthesis involves the
      activation of an unusual phosphatidylcholine-specific phospholipase C (PC-PLC)
      and not a phosphatidylinositol-specific phospholipase C (PI-PLC) or phospholipase
      D (PLD).

PMID- 7510955
TI  - A novel strategy for the investigation of clonality in precancerous disease
      states and early stages of tumor progression.
AB  - A novel strategy for clonality determination from only 100 cells using the
      polymerase chain reaction in amplifying a 511 bp region located within the first
      intron of the human hypoxanthine phosphoribosyl transferase (HPRT) gene has been
      devised. The strategy rests on several observations: that this region in females
      contains two HpaII/MspI sites whose methylation remains both obligate with X
      chromosome inactivation and independent of tumor progression; and that this
      region contains single base allelic polymorphisms in 5-10% of females which can
      be detected by denaturing gradient gel electrophoresis (DGGE) on the PCR product.
      In polymorphic individuals, multiple bands (homo- and heteroduplexes) indicate
      multiclonality, single bands indicate monoclonality, and their comparative
      migrations indicate clonal identity/non-identity.

PMID- 7510956
TI  - Topoisomerase I-inhibition enhances vitamin D-responsive expression of the
      receptor for lipopolysaccharide binding protein CD 14.
AB  - Pretreatment (4h) of human HL 60 leukemia cells with the topoisomerase I
      inhibitor camptothecin (7-28 x 10(-9) Mol/l, single dose) enhanced vitamin D3
      responsive CD 14 expression (10(-11)-10(-8) Mol/l vitamin D3) up to twofold, as
      measured by fluorescence activated flow cytometry after 1-3 days. Camptothecin by
      itself caused marginal effects. Hybridization of total RNA with oligonucleotides
      (bases 1358-1333 of CD 14 sequence) showed increased steady state levels of the
      1.75 kb CD 14 mRNA after 24 h when normalized to beta-actin. The nuclear
      accumulation of [3H]-vitamin D3/receptor complexes (VDR) in a nuclear
      translocation assay was significantly enhanced (by 3 h) in the presence of
      camptothecin. We conclude that inhibition of topoisomerase I enhances vitamin D3
      stimulated CD 14 expression. Topoisomerase I might either be a negatively active
      transcription factor itself or maintenance of DNA-bending, local supercoiling and
      accessibility of responsive elements might lead to reduction of VDR turnover and
      produce a stimulatory effect on vitamin D3-responsive transcription.

PMID- 7510958
TI  - Internalization of the alpha 5 beta 1 integrin does not depend on "NPXY" signals.
AB  - The alpha 5 beta 1 integrin is a constitutively internalized fibronectin
      receptor. It contains in the cytoplasmic tail of its beta 1 subunit two NPXY
      sequences which have been proposed to mediate internalization. Indeed a NPXY
      motif constitutes the internalization signal for the Low Density Lipoprotein
      (LDL) and insulin receptors. To learn more about the putative role of the two
      NPXY sequences in internalization of the alpha 5 beta 1 receptor, we have made
      and expressed mutants of the human beta 1 subunit in Chinese Hamster Ovary (CHO)
      cells, in which the two tyrosines of the NPXY motifs were replaced by serine
      residues. A cytoplasmic variant beta 1B which does not contain any NPXY sequence
      was also analyzed. Our results indicate that the NPXY mutants and the cytoplasmic
      variant are still internalized. Thus in the alpha 5 beta 1 receptor, the highly
      conserved NPXY sequences do not function as internalization motifs.

PMID- 7510957
TI  - Lysyl oxidase cDNA of myofibroblast from mouse fibrotic liver.
AB  - In order to study the regulation of lysyl oxydase (LO) in fibrosis, mRNAs were
      extracted from an enriched population of myofibroblasts (MF) isolated from liver
      of schistosomiasis infected mouse. Four mRNAs (5.5kb, 4.5kb, 2.4kb and 2.0kb)
      hybridizing with a LO cDNA probe were transcribed in fibrotic liver, but only the
      two largest mRNAs were found in MF. A cDNA library was constructed, allowing the
      cloning of twenty four cDNAs. The largest clone of 4689bp should correspond to
      the 5.5kb mRNA. Its sequence was essentially similar to the NIH-3T3 fibroblasts
      LO-ras recision gene (rrg4) cDNA, with the same exon/intron structure, but with
      some differences at the sites of initiation of transcription which were shown to
      occur mainly at -392 and -358 nucleotides before the putative start of
      translation. These two main sites of initiation did not explain the origin of the
      4.5kb and 5.5kb mRNAs, and as no spliced variants were found among the 24 clones,
      some regulation should also involve the 3'end region.

PMID- 7510959
TI  - The role of individual Fc gamma receptors in aggregated IgG-stimulated protein
      tyrosine phosphorylation in the human neutrophil.
AB  - Having previously shown that heat-aggregated IgG stimulates a significant
      increase in tyrosine phosphorylation in the human neutrophil, we next sought to
      determine the role of individual Fc gamma receptors in this response. Specific
      cross-linking of Fc gamma RII reproduced the phosphorylation observed with heat
      aggregated IgG treatment and monoclonal antibodies recognizing the ligand binding
      domain of Fc gamma RII efficiently blocked the heat-aggregated IgG induced
      response. Thus engagement of Fc gamma RII alone appears sufficient to mimic the
      heat-aggregated IgG stimulation. Similar experiments carried out with antibodies
      specific for Fc gamma RIII suggested that Fc gamma RII and Fc gamma RIII may
      cooperate in the phosphorylation response. The activation of a tyrosine kinase by
      Fc gamma R engagement was demonstrated by the specific immunoprecipitation of
      several tyrosine phosphorylated proteins from lysates of neutrophils following
      treatment with aggregated IgG.

PMID- 7510961
TI  - Synergism between platelet activating factor and C-C chemokines for arachidonate
      release in human monocytes.
AB  - Monocyte Chemotactic Protein(MCP)-1 and other members of the C-C branch of the
      chemokine superfamily (RANTES, MIP1 alpha/LD78, and MCP-3) induced, at
      chemotactic concentrations, the release of [3H]arachidonic acid in prelabeled
      human monocytes. Arachidonate release was potentiated (2 to 4 fold) in the
      presence of platelet activating factor (PAF). PAF effect was blocked by a
      specific receptor antagonist, WEB 2187, and was not present when inactive
      analogs, PAF inactive enantiomer, or lysoPAF were used. Thus, the synergistic
      action of PAF with C-C chemokines, in terms of arachidonate release and
      chemotaxis, is specific for this alkylphospholipid and is receptor mediated.
      Reciprocal potentiation of PAF and C-C chemokines may be important at sites of
      inflammation.

PMID- 7510962
TI  - Porcine luteal cells express monocyte chemoattractant protein-1 (MCP-1): analysis
      by polymerase chain reaction and cDNA cloning.
AB  - RT PCR employing poly(A+)RNA from porcine luteal cells and a combination of
      primers designed from the known bovine MCP-1 cDNA identified the luteal cells as
      a source of MCP-1. This finding is corroborated by results from Northern analysis
      using total RNA from luteal cells. To characterize the complete porcine MCP-1
      cDNA, poly (A+)RNA was isolated from porcine corpus luteum, transcribed into cDNA
      and the latter cloned into the expression vector lambda Uni-ZapXR. A digoxigenin
      labeled DNA probe of 375 bp was obtained by PCR and employed to screen the
      library. From the positive clones pMCP5, pMCP7 and pMCP10, the clone pMCP5 was
      selected and both strands of the cDNA insert were sequenced. The cDNA insert was
      742 bp long, with an open reading frame (ORF) encoding a protein of 99 amino acid
      residues which by comparison with known amino acid sequences of MCPs yielded
      highest identities with MCP-1 sequences. We therefore assume that pMCP5 encodes
      the amino acid sequence for porcine MCP-1.

PMID- 7510960
TI  - Ca(2+)-dependent activation of phospholipases C and D from mouse peritoneal
      macrophages by a selective trigger of Ca2+ influx, gamma-hexachlorocyclohexane.
AB  - The gamma-isomer of hexachlorocyclohexane (gamma-HCCH), which displays structural
      homology with inositol, was found to induce an initial influx of Ca2+ in mouse
      peritoneal macrophages. This was responsible for Ca(2+)-induced Ca2+ release via
      inositol 1,4,5-trisphosphate produced by phospholipase C and resulted in a
      sustained increase of cytoplasmic free Ca2+ concentration ([Ca2+]i). Entry of
      Ca2+ evoked by gamma-HCCH also stimulated phospholipase D, as well as the
      generation of reactive oxygen species formed by NADPH oxidase. These data suggest
      that some isoform(s) of phospholipase C, and possibly phospholipase D, can be
      activated by strictly Ca(2+)-dependent mechanisms. They also describe a new
      experimental tool allowing to trigger a selective influx of Ca2+. gamma-HCCH
      could thus be used in further studies aimed to delineate the role of Ca2+ entry
      in the subsequent activation of other signalling pathways.

PMID- 7510963
TI  - Sequence analysis and expression of phospholipase A2 from Taiwan cobra.
AB  - Polymerase chain reaction (PCR) was employed to amplify cDNAs constructed from
      the poly(A)+RNA of venom glands in Taiwan cobras to facilitate the cloning and
      sequencing of phospholipase A2 (PLA2) gene. The PCR product was then subcloned
      into pUC18 vector and transformed in E. coli strain JM109. Plasmids purified from
      the positive clones were prepared for nucleotide sequencing by dideoxynucleotide
      chain-termination method. Sequencing several clones containing about 0.5 kb DNA
      inserts constructed a complete and unambiguous full-length reading frame of 468
      base pairs covering a precursor for phospholipase A2 with a deduced mature
      protein sequence of 119 amino acids and a 27 amino-acid segment of signal
      peptide. The sequenced major PLA2 with pI 4.991 shows a high degree of sequence
      homology to those PLA2 of the same or closely-related genus. The deduced protein
      sequence allows us to correct and resolve some discrepancy between the sequences
      determined by conventional protein sequencing (Toxicon, 19, 141(1981)) and X-ray
      crystallography (Science, 250, 1560(1990)). Expression of PLA2 in E. coli vector
      generated a polypeptide which can cross-react with the antiserum against the
      native and purified PLA2 from the same cobra venom albeit with a much lower
      activity.

PMID- 7510964
TI  - Activation of macrophages by Alzheimer beta amyloid peptide.
AB  - Microglia (brain resident macrophages) have been found to be closely associated
      with beta amyloid containing plaques in brain tissue affected by Alzheimer
      disease (AD). To investigate whether beta amyloid peptide (beta AP) may activate
      microglia, the effects of synthetic beta AP (amino acids 1-40) and a subfragment
      (amino acids 25-35) on rat peritoneal macrophages were assessed using four
      different assays for activation. These peptides were compared with substance P,
      which has previously been shown to activate macrophages. Both beta amyloid
      peptides activated macrophages, as assessed by increased respiratory burst
      associated oxygen consumption, by luminol-dependent chemiluminescence, and by
      aggregation. In addition, beta amyloid peptide (1-40) caused a significant
      increase in macrophage nitric oxide production, while subfragment (25-35) did
      not. Substance P caused significant activation as assessed by oxygen consumption
      and chemiluminescence, but not by aggregation or nitric oxide induction.

PMID- 7510965
TI  - In vitro inhibition, by loratadine and descarboxyethoxyloratadine, of histamine
      release from human basophils, and of histamine release and intracellular calcium
      fluxes in rat basophilic leukemia cells (RBL-2H3).
AB  - The effect of the H1-antihistamine drug loratadine and its active metabolite
      descarboxyethoxyloratadine upon histamine release was examined on anti
      immunoglobulin E (IgE) triggered human basophils and 2,4-dinitrophenyl (DNP)
      triggered rat basophilic leukemia (RBL-2H3) cells. In both experimental systems,
      dose-dependent inhibition of histamine release was observed at
      descarboxyethoxyloratadine and loratadine doses above 2 and 7 microM,
      respectively. In the RBL-2H3 experimental system, inhibition by loratadine
      increased when the concentration of extracellular Ca2+ was reduced from 1.8 to
      0.45 mM. We further investigated the effect of loratadine and
      descarboxyethoxyloratadine on the increase in cytosolic calcium concentration
      (Ca2+)i, an early step in biochemical events leading to exocytosis. The effect of
      these two drugs upon (Ca2+)i changes was measured using the fluorescent probe
      fura-2 loaded into RBL-2H3 cells passively sensitized with DNP-specific IgE. Both
      drugs inhibited, in a dose-dependent manner (2.5-25 microM), the (Ca2+)i rise
      induced by DNP-BSA challenge in sensitized RBL cells, a process observed in both
      the presence and absence of extracellular Ca2+. Loratadine also inhibited the
      Mn2+ influx into these cells, thus reflecting the Ca2+ influx. These results
      suggest that loratadine and descarboxyethoxyloratadine impair the increase in
      (Ca2+)i following cell activation by decreasing both the influx of extracellular
      Ca2+ and the release of Ca2+ from intracellular stores.

PMID- 7510966
TI  - Transcriptional regulation of differentiation, selective toxicity and ATGCAAAT
      binding of bisbenzimidazole derivatives in human melanoma cells.
AB  - To study the relationship between the structure of minor groove ligands and their
      affinity for specific DNA sequences that regulate gene transcription, three
      analogues of the A-T-specific DNA minor groove ligands Hoechst 33258 and Hoechst
      33342 were synthesized with 5, 8 or 12 carbons in an aliphatic chain attached to
      the phenolic oxygen of the molecule. There was a striking bimodal relationship
      between toxicity to HeLa cells and the lipophilicity of the five analogues,
      toxicity being low for the compounds with a free hydroxyl (Hoechst 33258) or a 12
      carbon substituent, yet high for the 5-carbon analogue. Selective killing of
      human melanoma cells compared with normal fibroblasts was observed for the
      Hoechst analogue with a 12-carbon chain attached. Hoechst 33258 itself was
      selectively toxic for the MM96E melanoma cell line compared with other cell
      lines, induced a highly dendritic morphology, increased tyrosinase activity and
      tyrosinase mRNA but decreased the level of gp75 (TRP-1) mRNA; message for a third
      pigment gene, Pmel-17, was unchanged. Tyrosinase activity was decreased in the
      resistant A2058 melanoma cell line and transcription was affected to a lesser
      extent than in MM96E. Expression of gp75 protein and two intermediate filament
      proteins was inhibited by Hoechst 33258 in MM96E cells. There was no major
      difference in the amount of 125I-Hoechst 33258 taken up by sensitive and
      resistant cells. Of the five derivatives studied, the parent drug Hoechst 33258
      and the 2-carbon analogue (Hoechst 33342) were found to have the most inhibitory
      effect on affinity of octamer binding proteins for the ATGCAAAT consensus
      sequence found in the promoter region of certain genes associated with
      proliferation and differentiation. In contrast to Distamycin A (also an A-T
      specific minor groove ligand), Hoechst 33258 displaced proteins already bound to
      the octamer motif. The G-C ligand chromomycin A3 exhibited a different spectrum
      of cell toxicity and tyrosinase stimulation compared with Hoechst 33258.
      Chromomycin A3 but not Hoechst 33258, strongly inhibited the zinc-dependent
      transcriptional activity of the sheep metallothionein-Ia promoter in reporter
      gene assays of transfected cells. Since the six metal-responsive elements of the
      promoter are GC-rich, this provides independent evidence for the sequence
      specificity of transcriptional inactivation by one of these drugs in melanoma
      cells. Overall, the results suggest that Hoechst 33258 acts by inhibiting the
      transcription of specific genes, cell lines evidently differing in the
      accessibility to drugs of certain A-T-rich sequences.

PMID- 7510967
TI  - [The epidemiological aspects of head trauma due to road accidents. The cases of a
      hospital emergency service].

PMID- 7510968
TI  - [Environmental disinfection in the hospital: monitoring criteria and a comparison
      between different intervention methods].

PMID- 7510971
TI  - Clinic-statistical essay on the physiological (locomotory) ageing founded on a
      new approach.

PMID- 7510970
TI  - [The prevention of AIDS in prisons: a cognitive study of the attitudes and
      beliefs of 30 seropositive ex-detainees].

PMID- 7510969
TI  - [The evolution of European Community policies in the areas of the environment,
      research and worker hygiene and safety after the Treaty of Maastricht].

PMID- 7510972
TI  - [Emergency services and the prevention of tetanus. A study performed at 2 main
      hospitals of Cagliari].

PMID- 7510973
TI  - An information system for the surveillance of zoonoses and risk factors in animal
      farming and related industries in the Mediterranean area. 1: A methodological
      proposal.

PMID- 7510974
TI  - [Typhoid fever due to multiresistant Salmonella typhi: an epidemiological study
      in Lombardy].

PMID- 7510976
TI  - [The chemical and physicochemical aspects of treating water with ultraviolet rays
      and hydrogen peroxide].

PMID- 7510975
TI  - [The treatment of swimming pool water in light of the new standard].

PMID- 7510977
TI  - [The treatment of swimming pool water with ultraviolet rays and hydrogen
      peroxide. Experiences in the laboratory and in the field].

PMID- 7510979
TI  - [Experience with anti-Haemophilus influenzae type B vaccination in children under
      2 years of age].

PMID- 7510978
TI  - Adverse reactions to vaccine: Italian cases in the quinquennium 1986-1990.

PMID- 7510981
TI  - Rapid isolation of nuclei from carrot suspension culture cells using a
      BioNebulizer.
AB  - The BioNebulizer is an instrument that breaks cells and large molecules using the
      shearing forces created by laminar flow of high-pressure gas in the
      microcapillary channels generated by the instrument. Within 4 min, 90% of the
      carrot suspension culture cells that passed through the nebulizer were broken.
      Cytosol and organelles were released from the broken cells leaving cell wall
      ghosts. Nuclei were further purified by means of a discontinuous Percoll
      gradient. This method yielded an average of 2 x 10(5) nuclei from 2 g of
      suspension culture cells (approximately 2 x 10(6) cells). The isolated nuclei
      actively incorporated [8,5'-3H]-GTP into RNA.

PMID- 7510980
TI  - Epidemiological study on alcohol consumption trends and on the effects of alcohol
      consumption on the human body. Note 2: Levels of lead in red wine from a northern
      Italian region.

PMID- 7510982
TI  - An improved rapid method of isolating RNA from cultured cells by SDS-acid
      phenol/chloroform extraction.

PMID- 7510983
TI  - Regional expression of CFTR in developing human respiratory tissues.
AB  - Morbidity and mortality in cystic fibrosis (CF) patients is strongly related to
      their respiratory disease. We have analyzed, by means of in situ hybridization,
      the localization and levels of CFTR mRNA in fetal, newborn, and infant
      respiratory tissues. Measurable levels of CFTR transcript are present in the
      fetal primordial epithelium of the pseudoglandular stage lung. During the
      following stages of lung development, CFTR expression decreases in cells of the
      future alveolar spaces and is gradually limited to the epithelium of the small
      airways. After birth, expression decreases in the small airways and is not
      detected in alveolar epithelia. In trachea and large bronchi, a differential
      pattern of expression is also observed. No CFTR expression is found in fetal
      submucosal glands during fetal development, but appears gradually in the newborn
      period. Since CFTR codes for a secretory Cl- channel, these data probably reflect
      the changes that occur in the lung transition from a fluid-secreting to an
      absorbing organ. The pattern of expression seems paradoxical in view of the
      clinical-pathological manifestations of CF. Although CFTR is expressed in the
      normal fetus and lung development is influenced by the amount of fetal lung
      liquid, newborns affected with CF have normal lungs. In addition, the earliest
      pathologic change described in CF lungs in hyperplasia of the submucosal glands,
      yet expression in these structures is seen only after birth. An improved
      understanding of the factors that alter the expected relationship between CFTR
      expression and pathologic lesions in the fetal lung may provide important
      insights into the pathogenesis and potential treatment of lung disease in CF
      patients.

PMID- 7510984
TI  - Identification of IgE-bearing cells in the late-phase response to antigen in the
      lung as basophils.
AB  - We have carried out studies to ascertain whether the histamine-containing, IgE
      bearing cells found in the bronchoalveolar lavage (BAL) fluid obtained during the
      late-phase response following subsegmental antigen challenge of human airways are
      predominantly basophils or mast cells. Four lines of evidence suggest that most
      are basophils: (1) The cells fulfill morphologic criteria for light microscopy.
      (2) Cell surface markers determined by immunofluorescence and flow cytometry
      revealed that the IgE-bearing cells express the leukocyte antigens Fc gamma RII
      and the beta 2 integrins, LFA-1 and Mac-1, but do not express the mast cell
      associated c-kit receptor for stem cell factor. (3) The late-phase histamine
      containing cells in late-phase BAL fluids have the functional characteristics of
      basophils in their secretory responses to anti-IgE, the f-met peptide, and
      phorbol ester TPA. (4) The cells have a functional histamine type 2 receptor, a
      characteristic of basophils, not mast cells. We conclude that basophils
      infiltrate the lower airways hours after antigen exposure. These cells may be
      responsible for the mediator release observed at that time.

PMID- 7510985
TI  - Disparate role of the beta 2-integrin CD18 in the local accumulation of
      neutrophils in pulmonary and cutaneous inflammation in the rabbit.
AB  - The leukocyte adhesion glycoprotein complex CD11/CD18 has been shown to be
      important in mediating neutrophil accumulation at sites of inflammation in many
      experimental models. The exception is the lung, where neutrophil accumulation
      into the airspaces can be CD18-dependent and -independent, according to the
      stimulus used to induce pulmonary inflammation. By using the anti-CD18 mAb 60.3,
      this study examined the role of CD18 on neutrophil accumulation in the lungs of
      rabbits induced by a local intrabronchial instillation of C5a or interleukin-1
      alpha (IL-1 alpha) into the upper lung lobes. For comparison, cutaneous
      inflammation was induced in the same animals by intradermal injection of the same
      mediators. Pretreating rabbits with 60.3 abolished accumulation of 111In-labeled
      neutrophils in skin induced by both C5a and IL-1 alpha. In contrast, in the same
      animals, C5a-induced accumulation of neutrophils in the lung was not
      significantly affected by 60.3, while neutrophil accumulation in response to IL-1
      alpha showed a significant, but not absolute, dependency on CD18. External gamma
      scintigraphy of 111In-labeled neutrophils demonstrated that the kinetics of cell
      retention in the lung was similar for both C5a and IL-1 alpha. In summary,
      accumulation of neutrophils to sites of inflammation in cutaneous inflammation
      shows an absolute dependency on CD18, while migration of these cells to sites of
      inflammation in the lung can be largely independent of this adhesion molecule.
      These data indicate that the mechanisms responsible for accumulation of
      neutrophils in cutaneous and pulmonary inflammation are different.

PMID- 7510986
TI  - Scleroderma bronchoalveolar lavage fluid contains thrombin, a mediator of human
      lung fibroblast proliferation via induction of platelet-derived growth factor
      alpha-receptor.
AB  - In addition to its procoagulant properties, the serine protease thrombin
      increases endothelial permeability, stimulates granulocyte adherence, and serves
      as a fibroblast mitogen. We demonstrate that thrombin is mitogenic for human lung
      fibroblasts in vitro. The mitogenic effect of thrombin is associated with an
      increase in the expression of the ligand PDGF-AA and up-regulation of PDGF alpha
      receptor. Since scleroderma (systemic sclerosis; SSc) is characterized by
      widespread microvascular injury and is frequently complicated by pulmonary
      fibrosis, we sought to determine the level of thrombin activity in
      bronchoalveolar lavage (BAL) fluid from SSc patients and normal controls. We
      report a significantly higher level of thrombin activity in BAL fluid from SSc
      patients compared with normal controls (P < 0.001). Taken together, the high
      levels of thrombin in BAL fluid and its demonstrated mitogenicity for lung
      fibroblasts suggest an important role for thrombin in the pathogenesis of SSc and
      perhaps other fibrotic lung diseases.

PMID- 7510987
TI  - Heterogeneity of sulfated microdomains within basement membranes of pulmonary
      airway epithelium.
AB  - The purpose of this study was to determine whether the cytochemically defined
      distribution of sulfated macromolecules is significantly different in
      microdomains of basement membranes (BMs) associated with different levels of
      pulmonary airways. The high iron diamine-thiocarbohydrazide-silver proteinate
      (HID-TCH-SP) technique, which is highly specific for sulfate esters of
      glycosaminoglycans and some glycoproteins, was used as a probe to compare the BM
      of trachea, bronchi, and three different sizes of bronchioles. When HID-reactive
      sites were counted and statistically compared, significant differences were found
      between the three known anatomically distinct layers of the BM--lamina lucida
      (LL), lamina densa (LD), and lamina reticularis (LR)--relative to the airway
      level. The highest concentration of HID reactivity in trachea, bronchi, and large
      bronchiole was found in LR and the lowest in LD. By comparison, HID-reactive
      sites were found to be more concentrated in the LL in medium and small
      bronchioles. HID reactivity was consistently low in LD as compared with LL and LR
      in all five locations. The overall degree of HID reactivity in BMs was clearly
      highest in large bronchioles and lowest in medium and small bronchioles. This
      cytochemically detectable heterogeneity in the distribution of HID reactivity in
      BM microdomains may represent specific compositional differences in pulmonary BMs
      which are important determinants of epithelial cell function and might be
      expected to impact key biologic processes in normal and pathologic states.

PMID- 7510988
TI  - [Cancer of the distal pancreas: comments on its diagnosis and therapy].
AB  - The authors report 14 cases of neoplasms involving the pancreatic body and tail.
      Duration and characteristics of symptoms at outbreak, diagnostic work-up,
      resection rates, morbidity and operative mortality are statistically analysed and
      compared with those found in the same period in patients with cancer of the
      pancreatic head. A number of important differences between these two locations
      are detected and analytically discussed.

PMID- 7510989
TI  - Cytokine gene expression in human multiple myeloma.
AB  - In the present study the gene expression of cytokines promoting in vitro myeloma
      cell growth was investigated by Northern blot analysis using total RNA of 36
      tumour samples of patients with multiple myeloma (MM) or plasma cell leukaemia
      and poly(A)+ RNA of 10 human myeloma cell lines (HMCL). These cytokines included
      interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granulocyte-macrophage (GM)
      colony-stimulating factor (CSF) and granulocyte (G)-CSF. IL-1 beta, IL-6 and G
      CSF genes were coexpressed in most patients, although at variable levels. IL-1
      alpha transcripts were detected in 32% of patients in whom coexpression of IL-1
      beta gene was found. IL-3 gene was not expressed in patients' cells and GM-CSF
      mRNA was detected in only 1/32 patients. No detectable transcripts for the above
      cytokines were present in HMCL, whereas IL-6 gene was expressed in 2/10 HMCL. We
      also looked for the presence of transcripts for IL-2, leukaemia inhibitory factor
      (LIF) and transforming growth factor (TGF)beta in cells of tumour samples from
      the same patients and in HMCL. IL-2 gene was not expressed in MM patients and
      HMCL. Weak expression of LIF gene was detected in three patients (9%), and
      transforming growth factor beta (TGF beta) mRNA was observed in 12/12 tumour
      samples analysed and all HMCL. These results suggest that, among cytokines shown
      to control myeloma-cell growth in vitro, IL-1, IL-6 and G-CSF could play a role
      in the development of myeloma disease in vivo.

PMID- 7510990
TI  - Aprotinin reduces cardiopulmonary bypass-induced blood loss and inhibits
      fibrinolysis without influencing platelets.
AB  - Cardiopulmonary bypass (CPB) induces a bleeding defect which leads to enhanced
      blood loss. A double-blind study was carried out comparing aprotinin with placebo
      in patients undergoing re-operation for heart valve replacement. The results
      confirm that aprotinin is effective at reducing such loss. In the placebo treated
      group, significant increases were observed, during CPB, in the plasma
      concentrations of fibrinolytic activity, tissue plasminogen activator antigen, D
      dimer, and beta-thromboglobulin. Platelet counts fell within 5-10 min of the
      patients going onto CPB, but this could be accounted for by the dilutional effect
      of the extracorporeal circuit. Inhibition of responsiveness of platelets, as
      judged by aggregometry, was significant only at the end of bypass when collagen
      was the agonist and after protamine reversal when ristocetin was the agonist. CPB
      did not enhance the release, into the circulation, of glycocalicin (a proteolytic
      fragment of glycoprotein Ib). In the aprotinin-treated group, the formation of
      fibrin degradation products as measured by D-dimer was inhibited. However,
      aprotinin did not influence the change in platelet count, suppress beta
      thromboglobulin release from platelets, prevent the inhibition of platelet
      function or influence the concentration of plasma glycocalicin during the study
      period. These observations confirm that CPB leads to a fibrinolytic state and
      less responsive platelets. This study also indicates that aprotinin-induced
      reduction in blood loss is associated with inhibition of plasmin-mediated fibrin
      digestion and that the mechanism by which aprotinin reduces blood loss is not via
      protection of platelets during CPB.

PMID- 7510991
TI  - Evaluation of leukaemic contamination in peripheral blood stem cell harvests by
      reverse transcriptase polymerase chain reaction.
AB  - A major issue in autologous blood stem cell transplantation (ABSCT) for leukaemia
      is whether peripheral blood stem cell (PBSC) harvests are less contaminated with
      leukaemic cells than bone marrow mononuclear cells (BMMNC). We compared leukaemic
      contamination in PBSC harvests and BMMNC, obtained simultaneously, by using
      reverse transcriptase polymerase chain reaction (RT-PCR) of leukaemia-specific
      chimaeric messenger RNA (mRNA), in three patients with Philadelphia chromosome
      (Ph)-positive acute lymphoblastic leukaemia (ALL), one with Ph-positive acute
      myelogenous leukaemia (AML), and two with acute promyelocytic leukaemia (APL).
      Our two-step PCR method employed 'nested primers' in the second step and can
      detect one leukaemic blast diluted into 10(6) HL-60 cells. In three of four
      patients with Ph-positive ALL and AML we detected leukaemic contamination in both
      PBSC harvests and BMMNC. In the remaining patient with ALL, both PBSC harvests
      and BMMNC were PCR-negative. Both PBSC harvests and BMMNC from one patient with
      APL were PCR-positive. In contrast, PBSC harvests from another patient with APL,
      whose BMMNC could not be obtained because of bone marrow necrosis, were PCR
      positive after the first course of consolidation chemotherapy, but became PCR
      negative after the second course. The present study does not support the
      hypothesis that PBSC harvests are less contaminated by leukaemic cells than
      BMMNC, but suggests that PBSC harvests are contaminated when BMMNC are
      contaminated.

PMID- 7510993
TI  - Sustained trilineage response in a patient with ALG-resistant severe aplastic
      anaemia after treatment with G-CSF, erythropoietin and cyclosporin A: association
      of recovery with marked elevation of serum alkaline phosphatase.
AB  - Aplastic anaemia is characterized by multilineage bone marrow failure resulting
      in pancytopenia. We have successfully treated a young woman with severe aplastic
      anaemia (SAA) who was resistant to antilymphocyte globulin (ALG) and
      corticosteroids, with a combination therapy consisting of erythropoietin,
      cyclosporin A and granulocyte-colony stimulating factor (G-CSF). The patient
      received erythropoietin and CSA for a period of 10 months without success before
      G-CSF treatment was started. After 6 weeks of G-CSF therapy she responded with a
      sustained trilineage recovery. This suggests that immunosuppression together with
      haemopoietic growth factors may be an effective treatment in patients with SAA
      who are ALG resistant and cannot be treated by BMT.

PMID- 7510992
TI  - Effect of different human immunodeficiency virus type-1 (HIV-1) isolates on long
      term bone marrow haemopoiesis.
AB  - Haemopoietic cytopenias are a frequent occurrence in human immunodeficiency virus
      type-1 (HIV-1) induced disease. In order to examine the possible direct
      inhibition of marrow haemopoiesis by HIV-1, we have investigated the effect of
      HIV-1 infection on myelopoiesis in long-term bone marrow cultures. In vitro
      exposure of normal marrow cultures to three different lymphocytotropic HIV-1
      isolates resulted in productive infection, as demonstrated by a progressive
      increase of gag p24 antigen. In these experiments, ICR-3 isolate, but not LAV' or
      NL4-3 isolates, accelerated the loss of non-adherent cells. A differential
      ability of these HIV-1 isolates to suppress myelopoiesis was confirmed in long
      term cultures in which virus was added continuously. In these cultures, ICR-3,
      and to a lesser extent also NL4-3, but not LAV', induced a progressive decrease
      in the number of total non-adherent cells as well as non-adherent colony forming
      units-granulocyte/macrophage (CFU-GM). Furthermore, exposure of normal purified
      CD34+ cells to ICR-3 induced defects in their ability to form haemopoietic
      colonies; this inhibitory effect was significantly relieved by pretreatment of
      ICR-3 with an anti-gp120 antibody. Similar exposure of CD34+ cells to LAV' and
      NL4-3 induced no such defects. These data indicate that some HIV-1 isolates can
      impair bone marrow haemopoiesis in a dose-dependent fashion, acting, at least in
      part, at the level of haemopoietic stem/progenitor cells.

PMID- 7510994
TI  - Interaction of hepatitis B and hepatitis C infection in haemophilia.
AB  - The management of haemophilia has been greatly complicated by the clinical
      sequelae of viral infection acquired through contaminated blood products. Many
      haemophiliacs have been infected by several viruses and the interaction between
      these viruses may be complex. In a cohort of 42 anti-HCV positive haemophiliacs,
      five were also found to be positive for HBsAg. All five were HCV reverse
      transcriptase/PCR negative compared to the 4/37 (11%) anti-HCV positive
      haemophiliacs who were HBsAg negative (P = 0.0001). We have identified a striking
      interaction between hepatitis C (HCV) and hepatitis B (HBV) in haemophiliacs co
      infected by these agents, suggestive of the phenomenon of viral interference.

PMID- 7510995
TI  - Asynchronous expression of c-kit and CD34 on leukemic blasts.

PMID- 7510996
TI  - CD34 expression in de novo acute myeloid leukaemia.

PMID- 7510998
TI  - CD1 gene expression in human skin.
AB  - In human epidermis, expression of CD1a is confined to Langerhans cells (LC),
      whereas CD1c expression has been observed in dendritic cells of the dermis, as
      well as the epidermis. In transfected fibroblasts, expression of CD1c at the cell
      surface appears to exclude expression of either CD1b or CD1a, despite continued
      transcription of the latter genes. In order to determine whether this mechanism
      might be operative in human skin, we have compared the expression of CD1a and
      CD1c on the surface of dermal and epidermal dendritic cells to their expression
      at the level of mRNA using a combination of dual-label immunofluorescence
      microscopy, northern blot hybridization, and reverse transcriptase-polymerase
      chain reaction (RT-PCR). By both immunofluorescence and Northern blotting, CD1c
      expression was observed in both dermal and epidermal cells, whereas expression of
      CD1a was confined largely to the epidermis. Moreover, as shown by immunomagnetic
      bead selection and RT-PCR, CD1a and CD1c were both expressed on epidermal LC, but
      were absent from other epidermal cell types. These results argue against cell
      surface exclusion as a mechanism for selective expression of CD1c in human
      dermis.

PMID- 7510997
TI  - Effects of immunosuppressants FK506 and rapamycin on the heterooligomeric form of
      the progesterone receptor.
AB  - The non-DNA binding form of the rabbit uterus cytosol progesterone receptor (PR)
      contains, in addition to the hormone binding unit and heat shock protein M(r)
      90kDa (hsp90), a Heat shock protein Binding Immunophilin (p59/HBI) which
      interacts with hsp90. P59/HBI binds the immunosuppressants FK506 and Rapamycin
      (RAP) and belongs to the FK506 binding protein family. A recombinant p59/HBI
      glutathione-S-transferase fusion protein, purified by Sephadex LH-20 filtration
      of tritiated drug-p59/HBI complexes, binds FK506 and RAP with apparent Kd values
      of 75 +/- 40 and 40 +/- 15 nM, respectively. Immunopurification from cytosol of
      [3H]steroid-labeled tungstate-stabilized PR with anti-PR immunoadsorbent yielded
      "9S"-PR species in which hsp90, hsp70 and p59/HBI were present. In the absence of
      tungstate ions, only the 4-6S PR was eluted, and Western blot analysis
      demonstrated the absence of hsps and p59/HBI. In contrast 30 to 50% of the
      original 9S-PR species containing hsps and p59/HBI, was eluted in the absence of
      tungstate ions but after exposure of cytosol to 5 microM FK506 or RAP. Other
      experiments showed that cytosol fractions incubated for 2 h at 25 degrees C with
      0.05 to 10 microM FK506 or RAP, then with [3H]steroids (the agonist [3H]Org 2058
      or the anti-progestin [3H]RU486), contains greater amounts of 9S-PR species than
      that detected in non-immunosuppressant exposed control cytosol. Scatchard
      analysis showed an up to 2-fold decrease of the Kd value for both hormones
      following exposure to drugs, without modification of the number of steroid
      binding sites. Purification of cytosol PR on immobilized FK506 yields a 9S form
      still containing hsp90, hsp70 and p59/HBI associated to PR units. Altogether,
      these results suggest that binding of immunosuppressants to p59/HBI does not
      promote hsps dissociation from the receptor and, as a consequence, that
      inhibition of peptidyl-prolyl isomerase activity of p59/HBI by immunosuppressants
      binding does not transform (activate) PR in vitro. However, given the assumption
      that hsp90 binds to receptor and that p59/HBI binds hsp90 but not directly to
      receptor, immunosuppressants affect hormone binding by an unknown mechanism
      involving receptor associated proteins. In addition, we show that the chick
      oviduct cytosol 9S-PR, not displaced with the EC1 antibody specific for several
      mammalian p59/HBI, also binds to FK506 columns and can be eluted by exchange with
      either FK506 or RAP, suggesting that there is an avian HBI homolog.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7510999
TI  - Piroxicam has at least two epitopes for contact photoallergy.
AB  - We have demonstrated previously in guinea pigs that the induction of photocontact
      sensitivity to piroxicam (PXM) also induces a state of cross-reactive contact
      hypersensitivity to two compounds having structurally related elements,
      thimerosal (TMS) and thiosalicylate (TOS). The present study was conducted to
      determine whether oral administration of TOS would desensitize guinea pigs
      previously photosensitized with PXM. At the same time, the spectrum of
      reactivities against these compounds and against tenoxicam (TXM) which resembles
      only piroxicam was assessed by appropriate sensitizing and eliciting protocols.
      As expected, animals photosensitized to PXM developed reactivities against all
      four compounds, PXM and TXM (photosensitivity) and TMS and TOS (contact
      sensitivity). By contrast, photosensitization with TXM induced cross-reactivity
      only against PXM. Moreover, the induction of contact sensitivity against TMS or
      TOS induced photosensitive cross-reactivity to PXM, but not to TXM. Finally, the
      oral administration of TOS produced a transient desensitization only for TMS and
      TOS. These results suggest that photosensitization with PXM induces two distinct
      reactivities. The first reactivity cross-reacts with TMS and TOS and is
      suppressible with orally administered TOS. The second cross-reacts only with TXM
      and is not suppressible with oral TOS. We conclude that PXM acquires at least two
      distinct immunogenic epitopes when exposed to UVA irradiation.

PMID- 7511001
TI  - Nucleotide inhibitors and activators of retinal guanylyl cyclase.
AB  - The restoration of the dark state in retinal rod cells following illumination is
      due in part to resynthesis of cGMP. Retinal guanylyl cyclase specifically
      catalyzes the cyclization of GTP into cGMP in vivo. The reaction has been shown
      to involve the inversion of the configuration on the phosphate atom as
      demonstrated by conversion of the (SP) isomer of GTP alpha S to (RP)-cGMPS by
      guanylyl cyclase [Senter, P. D., Eckstein, F., Mulsch, A., & Bohme, E. (1983) J.
      Biol. Chem. 258, 6741-6745]. Since (RP-cGMPS is not a substrate for retinal
      phosphodiesterase, we were able to measure cyclase activity with greater
      reliability using this novel assay as opposed to other published procedures. This
      assay has allowed us to reinvestigate the effects of adenylyl nucleotides on
      cyclase activity and to search for selective inhibitors of the rod-specific
      enzyme. We have measured the cyclase activity using homogenates of rod outer
      segments and a reconstituted system composed of guanylyl cyclase in washed rod
      outer segment membranes and the purified guanylyl cyclase activating protein. Our
      results indicate that 100-200 microM ATP (and other adenylyl nucleotides)
      stimulates guanylyl cyclase activity approximately 2-fold and that the observed
      stimulation of enzyme activity is independent of the free calcium concentration.
      In contrast to other particulate guanylyl cyclases, which are synergistically
      stimulated by a peptide ligand and ATP, guanylyl cyclase activating protein does
      not potentiate the effect of ATP, suggesting that retinal guanylyl cyclase may be
      regulated differently. ATP changes the Vmax of retinal guanylyl cyclase without
      changing the Km for (SP)-GTP alpha S.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511002
TI  - Structure and tissue-specific expression of the aldo-keto reductase superfamily.
AB  - We previously identified multiple proteins structurally related to 3 alpha
      hydroxysteroid dehydrogenase in rat liver, lung, kidney, and testis ((1991) Arch.
      Biochem. Biophys. 291, 258-262). We further used these monoclonal antibodies to
      screen several lambda gt11 cDNA libraries derived from male rat liver, lung, and
      kidney. Five additional unique cDNA clones were isolated and sequenced; the
      proteins encoded by these cDNAs were found to exhibit 37-62% amino acid sequence
      homology to rat liver 3 alpha-hydroxysteroid dehydrogenase. Because these encoded
      proteins belong to the aldo-keto reductase superfamily, we named these proteins
      RAKa to RAKf. RAK represents rat aldo-keto reductase, and RAKa is the previously
      described rat liver 3 alpha-HSD. Northern blot analysis and reverse transcription
      polymerase chain reactions were performed to examine their expression in various
      tissues. Only RAKe, which resembles human aldehyde reductase, was ubiquitously
      expressed in liver, kidney, lung, and other tissues, while the remaining mRNAs
      were found to have a more tissue- and sex-specific distribution. Genomic blot
      analysis showed complex, yet distinctive, restriction band patterns when
      different cDNAs were used as probes, suggesting that these cDNA clones are
      products of different genes and more related gene(s) may exist.

PMID- 7511000
TI  - Neither cyclosporin A nor FK506 affects adenylate cyclase responses of fetal rat
      keratinizing epidermal cells (FRSK cells) at concentrations that inhibit
      thymidine incorporation.
AB  - It has been reported that various anti-psoriatic agents augment the beta
      adrenergic adenylate cyclase response that is defective in the psoriatic
      hyperproliferative epidermis. Recent evidence indicates that cyclosporin A (CsA)
      and FK506 show beneficial effects on psoriasis. Using fetal rat keratinizing
      epidermal cells (FRSK cells) we investigated the effects of these compounds on
      the adenylate cyclase system. These immunosuppressants had no effect on the
      adenylate cyclase responses of FRSK cells up to 1-10 microM concentration,
      although they significantly inhibited thymidine incorporation at concentrations
      more than 0.1 microM. There was no significant difference in the inhibitory
      effect on thymidine incorporation between CsA and FK506, despite that FK506 is a
      much more potent immunosuppressant than CsA.

PMID- 7511004
TI  - Retinal antigen specific lymphocytes, TCR-gamma delta T cells and CD5+ B cells
      cultured from the vitreous in acute sympathetic ophthalmitis.
AB  - CD5+ B lymphocytes and TCR gamma-delta T lymphocytes, phenotypes implicated in
      the pathogenesis of autoimmune disease, were isolated from the vitreous in a case
      of acute sympathetic ophthalmitis. These cells were obtained using a method which
      allows the selective maintainance in vitro of in vivo activated T lymphocytes.
      Dual colour flow cytometry showed that after 3 days culture in IL-2 containing
      medium 61% of cells were CD5/CD19 + ve and 41% CD3/TCR gamma delta + ve. Of the
      total CD3 + ve population, 15% were gamma/delta negative. These cells formed a
      population which also responded in a proliferation assay to retinal antigens.
      Histologically the eye showed a marked mononuclear cell infiltration of the
      retina, ciliary body and choroid. Granulomatous lesions within the choroid
      contained lymphocytes, plasma cells and multinucleate giant cells.
      Immunocytochemistry showed lymphocyte populations to be predominantly CD2 + ve
      CD3 + ve T lymphocytes of the CD4 sub-set. Distribution of monocytes/macrophages
      throughout the lesions and restriction of B-lymphocytes to granulomata were all
      consistent with a DTH type reaction. Despite immunosuppressive therapy, the
      expression of activation antigens HLA-DR and ICAM-1 on infiltrating and resident
      ocular tissue cells was high, although IL-2 receptor (CD25) expression was
      virtually absent. Flow cytometric analysis of peripheral blood cells prior to
      treatment with Cyclosporin-A showed systemic activation of lymphocytes, with high
      levels of HLA-DR and CD25 expression and a raised CD4/CD8 ratio.

PMID- 7511003
TI  - [Tenoxicam-induced agranulocytosis, with good response to colony stimulating
      factor (G-CSF)].

PMID- 7511005
TI  - Autoimmunity-prone B-1 (CD5 B) cells, natural antibodies and self recognition.
AB  - The delineation of distinct subsets committed to the production of antibodies
      with different antigen-binding activities supports the view of a
      compartmentalization and specialization of function in the B cell repertoire and
      is consistent with the hypothesis of a developmentally layered immune system; as
      originally proposed by Herzenberg and Herzenberg. On the basis of the data by
      Solvason and Kearney in the human fetus and our data in the adult, and in
      agreement with the findings of Herzenberg et al. and Hardy et al. in the mouse,
      we propose that the human B cell repertoire includes at least three distinct B
      cell subsets: B-1a cells, which develop from progenitors in the fetal splanchnic
      district, namely the omentum, and are maintained in adult life by virtue of their
      self-replenishing nature; B-1b cells, progenitors of which can be found in the
      splanchnic district and, perhaps, adult bone marrow; and, finally, B-2 cells,
      which arise in the fetal liver and are continuously replenished in adult life by
      progenitors in the bone marrow (Figure 5). The different B cells types are
      distinguished by their differential expression of surface CD5 and, perhaps, CD11b
      and CD14, their differential expression of CD5 mRNA, and the different classes
      and specificities of the Ig they produce (Figure 5). B-1 lymphocytes play a major
      role in autoimmunity and constitute the physiological equivalent of the
      neoplastic forms in various lymphoproliferative disorders, such as CLL and SLL,
      which are often associated with the production of monoclonal antibodies to self
      antigens. Human B-1a (CD5+ B) and B-1b (CD5- CD45RAlo B) cells are responsible
      for the production of natural (polyreactive and monoreactive) antibodies in the
      fetus, neonate, and adult, and can give rise to the autoantibody-producing cells
      characteristic of several autoimmune disease states. Our recent findings suggest
      that while in healthy subjects the majority of natural polyreactive antibodies is
      encoded in V genes in germline configuration, some polyreactive antibodies are
      encoded in somatically mutated V genes, in a fashion consistent with an antigen
      driven process of selection of such mutations. The nature of the antigen(s)
      involved in these selection processes remains to be determined. Under possibly
      different circumstances, the application of an antigen-driven process of clonal
      selection to B-1a and/or B-1b cells, previously committed to natural antibody
      production, can result in the generation of monoreactive high affinity and
      possibly pathogenic autoantibodies (Figures 5A and 5B).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7511006
TI  - Differences between human B cell subpopulations.

PMID- 7511007
TI  - Characterization of two human anti-DNA antibodies bearing the pathogenic idiotype
      8.12.
AB  - Antibodies against double stranded DNA (dsDNA) are characteristic of systemic
      lupus erythematosus (SLE) and have been implicated in disease pathogenesis. Up to
      one third of an SLE patient's anti-dsDNA antibodies can express the lambda L
      chain idiotype 8.12. Serum titers of this idiotype are elevated in 50% of SLE
      patients, and idiotypic antibodies are present in glomerular immune deposits
      associated with lupus nephritis. Two EBV transformed B cell lines, KS3 from a
      patient with SLE and SD6 from an individual without autoimmune disease, secrete
      8.12+ IgG antibodies that bind dsDNA. The 8.12+ lambda L chains of these anti-DNA
      antibodies are encoded by members of the V lambda II gene family; the KS3 heavy
      chain is encoded by a VH4-DM1-DQ52-JH6b-C gamma 1 gene rearrangement and the SD6
      heavy chain is encoded by a VH3-D21/9-JH6b-C gamma 1 rearrangement. Both of these
      monoclonal antibodies are somatically mutated: the KS3 antibody displays
      mutations in complementarity determining regions (CDRs) and the SD6 antibody in
      framework regions (FRs). The significance of these different patterns of mutation
      in two potentially pathogenic anti-DNA antibodies is discussed.

PMID- 7511008
TI  - The vomiting reflex and the role of 5-HT3 receptors.

PMID- 7511009
TI  - Spatio-temporal distribution of acidic and basic FGF indicates a role for FGF in
      rat lens morphogenesis.
AB  - As part of an investigation into the role of FGF in lens development, we have
      studied the distribution of both aFGF and bFGF during eye morphogenesis from
      embryonic days 10 to 18 (E10-E18) in the rat. For aFGF, reactivity was found only
      in ectoderm at E10, prior to contact between the optic vesicle and presumptive
      lens ectoderm. During lens placode formation (E11) there was a transient, diffuse
      reactivity for aFGF in anterior optic vesicle cells directly apposed to the
      labelled ectoderm of the lens placode. At E12 the diffuse reactivity of the lens
      placode had changed to a discrete localisation along the basolateral surfaces of
      differentiating cells in the lens pit. Similar reactivity was associated with
      neuroblasts along the inner margin of the optic cup. At the early lens vesicle
      stage (E13) the baso-lateral aFGF-like reactivity associated with elongating lens
      cells was more intense and extensive. From the late lens vesicle stage (E14) to
      E18, reactivity in the lens was increasingly restricted to the equatorial regions
      which incorporate the germinative and transitional zones. From E16 to E18, aFGF
      like reactivity in the retina was predominantly localised in the peripheral
      regions corresponding to the developing ciliary body and iris and in the central
      retina associated with ganglion cell axons. For bFGF, weak reactivity was
      detectable as early as E13 in the developing lens capsule and increased in
      intensity during lens development with the posterior capsule reacting more
      intensely than the anterior capsule. Retinal bFGF-like reactivity was first
      detected at E14, associated with differentiating ganglion cells in the central
      retina. From E16 to E18 the retinal ganglion cells showed increasing reactivity
      and the pattern of reactivity followed the centro-peripheral pattern of retinal
      development. Thus reactivity for aFGF is first detected in presumptive lens
      ectoderm and subsequently in optic vesicle cells which are closely associated
      with lens ectoderm. This raises the possibility that aFGF may be involved in
      inductive interactions between presumptive lens ectoderm and optic vesicle.
      Furthermore the localisation patterns established for both aFGF and bFGF during
      lens and retina morphogenesis suggest an important role for FGF in regulating
      their morphogenesis and growth.

PMID- 7511010
TI  - Changes in populations of HLA-DR+CD3+ cells and CD57-CD16+ cells in alopecia
      areata after corticosteroid therapy.
AB  - We investigated the populations of activated T (HLA-DR+CD3+) cells and natural
      killer (CD57-CD16+) cells in the peripheral blood of patients with various types
      of alopecia areata (AA) and noted any changes that occurred in the said
      populations after administration of local and systemic corticosteroid therapy. In
      type 2 (severe multiple AA and alopecia totalis) and type 3 (alopecia
      universalis), the mean percentages of HLA-DR+CD3+ cells and CD57-CD16+ cells were
      significantly higher when compared with those of the normal controls. The
      percentages of both subsets in type 1 (mild AA) and the normal controls were
      consistent. Twenty-four patients in types 2 and 3 had received corticosteroid
      treatment, and all patients experienced new hair growth. With the changes in
      disease activity, the populations of HLA-DR+CD3+ cells in these patients after
      corticosteroid therapy significantly decreased when compared with those recorded
      prior to treatment. Subsequent to treatment, the mean percentages of CD57-CD16+
      cells decreased to levels that were not significant relative to that of the
      normal controls. These findings indicate that HLA-DR+CD3+ and CD57-CD16+ cells in
      the peripheral blood of patients with AA may be correlated with the disease
      activity of AA.

PMID- 7511011
TI  - Organization of rodent auditory cortex: anterograde transport of PHA-L from MGv
      to temporal neocortex.
AB  - In the present study we analyzed the organization of the thalamocortical
      projections of the specific auditory relay nucleus of the thalamus, the ventral
      division of the medial geniculate body (MGv), using the anterograde axonal tracer
      Phaseolus vulgaris leucoagglutinin. All injections of MGv produced dense labeling
      of axonal fibers in temporal cortex. In all cases, labeled axons were
      predominantly concentrated in cortical layers III and IV and, to a lesser extent,
      at the junction of layers V and VI. Injections confined to the medial regions of
      MGv, and specifically to the ovoid nucleus of MGv (OV, pars ovoidea), resulted in
      anterograde labeling of TE1, with minor labeling of the ventral quarter of TE1,
      designated subarea TE1v. Injections placed in lateral regions of MGv and
      occupying the lateral ventral subnucleus (LV), or injections in the mediolateral
      center of MGv and occupying parts of LV and OV, also resulted in labeling of area
      TE1 and minor labeling of TE1v. However, these injections also produced labeling
      in areas TE2 and TE3. Thus, area TE1 (excluding subarea TE1v) receives heavy
      projections from all aspects of MGv and appears to be the core target of MGv.
      While regions of MGv also project to surrounding cortical belt areas, these
      projections tend to be lighter and to vary depending on the region of MGv
      examined. These results, together with other connectional findings, and
      cytoarchitectonic and physiological studies, suggest that TE1 (possibly excluding
      subarea TE1v) is the primary auditory cortex in the rat.

PMID- 7511012
TI  - Information cascade from primary auditory cortex to the amygdala: corticocortical
      and corticoamygdaloid projections of temporal cortex in the rat.
AB  - Corticocortical and corticoamygdaloid connections of temporal cortext and
      perirhinal cortex (PRh) were examined in the rat with the anterograde tracer
      Phaseolus vulgaris leucoagglutinin (PHA-L). Iontophoretic injections of PHA-L
      into area TE1 resulted in columnar axonal terminations in surrounding and
      contralateral regions of temporal neocortex and in the striatum, but not in the
      amygdala. Within temporal neocortex, labeled fibers were present locally in
      adjacent regions of TE1, as well as in TE2d, TE1v, TE3v, and TE2c. Injection of
      cortical areas TE1v, TE3v, and TE2c, which received projections from TE1, or
      injections of perirhinal periallocortex, which received projections from TE1v,
      TE2v, and TE3v, resulted in projections to the amygdala. The pattern of
      corticocortical and corticoamygdaloid projections differed among the divisions of
      auditory cortex. TE1 exhibited extensive ipsilateral and contralateral
      projections to temporal cortical regions and no projections to the amygdala. In
      contrast, areas of temporal neocortex ventral and posterior to TE1, including
      TE1v, TE3v, TE2c, and PRh, had more limited ipsi- and contralateral
      corticocortical projections but had an increased connectivity with the
      subcortical forebrain, especially the lateral nucleus of the amygdala (AL). There
      was a topographic organization to the AL afferents. The dorsal subdivision of AL
      received projections from TE1v, TE3v, TE2c, and PRh, while the ventrolateral
      division received projections from TE3v, TE2c, and PRh. The ventromedial division
      received projections only from PRh, which, unlike other temporal cortical areas,
      also projected to the basolateral and basomedial nuclei of the amygdala. These
      findings define the complete sequence of connections linking primary auditory
      cortex with the amygdala in the rat. In addition, the findings indicate that the
      ventral portion of TE1, designated TE1v, has connections that distinguish it from
      dorsal TE1, namely, dense projections to AL and a diminished number of
      corticocortical projections ipsilaterally and contralaterally. Finally, the
      results suggest a topographic organization to the cortical terminations within
      the amygdala.

PMID- 7511013
TI  - Transcriptional specificities of adriamycin.
AB  - The transcriptional effect of adriamycin using E. coli RNA polymerase on several
      single- and double-stranded DNAs of known base content and sequence is studied in
      vitro. The results show that adriamycin inhibits strongly and with little
      difference toward both poly[d(A-T)] and poly[d(G-C)] templates, and that it
      inhibits both single- and double-stranded DNA directed RNA synthesis, albeit the
      inhibition is clearly preferential to the double-stranded alternating copolymers
      over the double- and single-stranded homopolymers. Since adriamycin inhibition of
      RNA synthesis can be totally abolished when assayed in excess amount of DNA, the
      possibility that adriamycin may also directly inhibit the enzyme RNA polymerase
      per se is ruled out.

PMID- 7511015
TI  - Caprine arthritis-encephalitis virus: isolation and identification in Rio Grande
      do Sul, Brazil.
AB  - We describe the first report of caprine arthritis-encephalitis virus (CAEV)
      isolation in Brazil. In December 1989 a four-year old anglonubian arthritic doe
      was submitted to euthanasia and its synovial membranes were cultured by
      explantation. This doe was positive for antibodies to the caprine arthritis
      encephalitis virus (CAEV). The reverse transcriptase activity detected in culture
      supernatants, the characteristic cytopathic effect of lentivirus in these
      cultures, the detection of viral antigens in concentrated supernatants by the
      agar gel immunodiffusion test, and the results of the fluorescent antibody test
      and of Northern blot analyses are consistent with the isolation of the CAEV.

PMID- 7511014
TI  - Molecular cloning and physiological analysis of an invertase isoenzyme in
      Helianthus tissues.
AB  - A soluble acid invertase activity isolated from Helianthus tuberosus (Jerusalem
      artichoke) shoots and analyzed by immunochromatography using polyclonal yeast
      antibodies, represents around 5% of the total invertase activity. This invertase
      isoenzyme was also isolated from dormant tuber parenchyma. In these partially
      dormant tissues, the specific activity of this isoenzyme is low suggesting a
      partial inactivation of the invertase molecules. Polyacrylamide gel
      electrophoresis of immunopurified fractions yields similar levels of the 58 kDa
      polypeptide both in shoots and dormant tubers, but with much lower activity of
      the enzyme in the tubers. A cDNA library was constructed in pUEX 1 from poly (A)+
      RNA extracted from Jerusalem artichoke tubers. This library was screened for
      invertase using (i) a Bacillus subtilis invertase DNA probe and (ii) anti-yeast
      invertase antibodies. A recombinant clone of approximately 1.8 kb size was
      selected by these two methods. Using Northern blots, a temporal sequence in the
      expression of invertase gene was observed during the breaking of dormancy with
      the main level after 8 weeks of cold treatment at 4 degrees C. A 2.5 kb
      transcript was detected, translation of which would yield a 97 kDa polypeptide
      representing the precursor of Jerusalem artichoke invertase.

PMID- 7511016
TI  - G-CSF primed peripheral blood progenitor cells in autologous bone marrow
      transplantation: parameters affecting bone marrow engraftment.
AB  - G-CSF and GM-CSF enhance the rate of neutrophil engraftment in autologous bone
      marrow transplantation (ABMT) without significantly affecting platelet
      engraftment. Peripheral blood progenitor cells (PBPC) may enhance rates of
      engraftment of both neutrophils and platelets. We treated 49 patients undergoing
      ABMT with a course of G-CSF to obtain PBPC and infused these cells post
      transplant with G-CSF in an attempt to determine factors which might correlate
      with enhanced BM engraftment. Forty-nine patients with Hodgkin's disease, non
      Hodgkin's lymphoma or breast cancer undergoing unpurged ABMT were studied. G-CSF
      priming consisted of an outpatient 8 day course of 5 micrograms/kg/day followed
      by three leukaphereses (on day 5, 7 and 8) to collect PBPC. Patients then
      received a chemotherapeutic BMT preparative regimen followed by an infusion of
      PBPC, autologous BM and the reinstitution of G-CSF (16 micrograms/kg/day). BM
      engraftment was rapid. The median time to achieve 0.5 x 10(9)/l neutrophils was
      10 days compared with a historical BMT control patient population receiving the
      same preparative regimens of 19 days (p = 0.001). Time to achieve a platelet
      count of 20 x 10(9)/l was 16 days compared with a historical control of 22 days
      (p = 0.001). Neutrophil engraftment occurred in all patients by day +14. Marrow
      engraftment correlated with the total number of CD34+ cells infused as well as
      the total number of mononuclear cells infused but not the total number of
      CD34+/CD33- cells infused. The amount of total blood volume pheresed
      significantly correlated with yield of total mononuclear cells. Prior exposure to
      radiation therapy negatively correlated with progenitor cell yield.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7511018
TI  - Comparison of FM1-43 staining patterns and electrophysiological measures of
      transmitter release at the frog neuromuscular junction.
AB  - Frog motor nerve terminals were stained with the activity-dependent dye FM1-43,
      which appears to stain recycled synaptic vesicles. Superficial end plates which
      could be visualized in their entirety were imaged and end plate potentials (EPPs)
      evoked by low frequency nerve stimulation were recorded from the muscle fibers
      which were innervated by the imaged terminals. Curare was present to block muscle
      contractions. The amplitude of the EPPs correlated reasonably well with the
      number of fluorescent spots counted in the terminals (r = 0.68). Each fluorescent
      spot probably represents a cluster of synaptic vesicles localized at an active
      zone. Several other morphological and electrophysiological values were measured
      and calculated. The results are consistent with the ideas that FM1-43 stains
      recycled synaptic vesicles, and that the number of vesicle clusters in a terminal
      is a good predictor of synaptic efficacy.

PMID- 7511017
TI  - Autografting with peripheral blood stem cells mobilized by sequential interleukin
      3/granulocyte-macrophage colony-stimulating factor following high-dose
      chemotherapy in non-Hodgkin's lymphoma.
AB  - This report summarizes our results of sequential treatment with IL-3 and GM-CSF
      following high-dose chemotherapy with respect to the yield and composition of
      peripheral blood stem cells (PBSC). Eight patients with high-grade non-Hodgkin's
      lymphoma were included in the study. Starting 24 h after high-dose cytosine
      arabinoside (Ara C)/mitoxantrone, IL-3 was given for 6 days, followed by GM-CSF.
      The increase of circulating hematopoietic progenitor cells during leukocyte
      recovery varied substantially from patient to patient. Up to a 22-fold
      interindividual difference was observed for the peak levels of CD34+ cells. A
      special focus of our study was the antigenic profile of the CD34+ PBSC. On
      analysis of the antigenic profile of the CD34+ cells, the proportion of CD34+/HLA
      DR- and CD34+/CD38- cells representing non-committed hematopoietic stem cells was
      consistently < 5%. The vast majority of CD34+ cells was found to coexpress CD33
      (86.3 +/- 2.1%, mean +/- SEM), reflecting myeloid lineage commitment. CD71
      antigen was present on 47.4 +/- 3.0% CD34+ cells with two populations
      (CD71dim/bright), while the percentage of early B lymphoid (CD34+/CD19+)
      progenitor cells was extremely low (0.38 +/- 0.13%). We therefore conclude that
      the cytokines currently available such as G-CSF, GM-CSF or IL-3 facilitate an
      ontogenetic phenomenon supporting the redistribution of hematopoietic progenitor
      cells after cytotoxic treatment. Six patients were autografted with the IL-3/GM
      CSF-exposed blood stem cells following high-dose conditioning therapy. It is
      worth noting that no additional BM or hematopoietic growth factors were given
      post-transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511019
TI  - Ethnic and geographic perspectives in SLE.

PMID- 7511020
TI  - Profiles of cytokines (TNF alpha and IL-6) and acute phase proteins (CRP and
      alpha 1AG) related to the disease course in patients with systemic lupus
      erythematosus.
AB  - Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) play a main role
      in inducing acute phase protein production by hepatocytes. This study describes
      the serum levels of TNF alpha and IL-6 in relation to serum levels of C-reactive
      protein (CRP) and alpha 1-acid glycoprotein (alpha 1AG) in three systemic lupus
      erythematosus (SLE) patients. Disease courses of these patients were divided in a
      total of 19 clinical periods, according to the clinical symptoms and interleukin
      profiles. Significantly elevated TNF alpha levels were found in all but three of
      the defined periods, without being associated with disease activity. In only four
      of the defined periods elevated TNF alpha were observed combined with elevated IL
      6 and CRP levels. Two of these periods coincided with minor symptoms of SLE, one
      with an exacerbation and the other one with a systemic infection while SLE
      activity was low. All other periods showed varying combinations of elevated TNF
      alpha and/or IL-6 levels being followed or not by elevated CRP levels.
      Significantly raised alpha 1AG levels were measured in all clinical periods. In
      most of the observed periods a dissociation was found between TNF alpha and IL-6
      and also between the different cytokine (TNF alpha and IL-6) levels and acute
      phase protein (CRP and alpha 1AG) levels. These data could not be explained by
      differences in disease course or influences of medication. We conclude that more
      factors other than TNF alpha and IL-6 must play a role in the regulatory pathway
      of the acute phase response in SLE.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511021
TI  - Epidermolytic palmoplantar keratoderma cosegregates with a keratin 9 mutation in
      a pedigree with breast and ovarian cancer.
AB  - Epidermolytic palmoplantar keratosis (EPPK) cosegregates with breast and ovarian
      cancers in a large French pedigree, raising the possibility that a single genetic
      mutation might cause these conditions and offering a potential lead to the
      identification of a hereditary breast/ovarian cancer gene. We have performed
      linkage analysis and show that the EPPK locus lies on the long arm of chromosome
      17 near the type I keratin gene cluster and the proposed breast cancer gene
      (BRCA1). The type I keratin 9 gene has been partially sequenced in four affected
      individuals. A single base mutation within the rod domain of the protein
      cosegregates with EPPK in all affected individuals tested. Although inheritance
      of this mutation is likely responsible for EPPK, it is unlikely to be the cause
      of the breast and ovarian cancer.

PMID- 7511022
TI  - Epidermal disease: faulty keratin filaments take their toll.

PMID- 7511024
TI  - [Antiovulatory action of chlormadinone acetate].
AB  - Antiovulatory action of chlormadinone acetate (5 mg twice daily from day 7 to day
      25) has been assessed in 6 healthy volunteers by daily determination of plasma
      FSH, LH, estradiol and progesterone. Hormonal profiles during the second treated
      cycle show that preovulatory gonadotropin surge is blunted and that no
      significant progesterone secretion occurs. Estradiol production is variable up to
      the middle of the cycle, and then homogeneously low normal. Menstrual cyclicity
      is respected and ovarian function is restored during the first cycle after
      treatment disruption.

PMID- 7511025
TI  - Legionnaires' disease associated with hospitals.

PMID- 7511023
TI  - Safety and efficacy of repetitive adenovirus-mediated transfer of CFTR cDNA to
      airway epithelia of primates and cotton rats.
AB  - Gene therapy for cystic fibrosis (CF) will require the safe transfer of CFTR cDNA
      to airway epithelia in vivo. We showed previously that a recombinant adenovirus,
      Ad2/CFTR-1, expresses CFTR in vitro. As adenovirus rarely integrates, treatment
      will require repeated vector administration. We applied Ad2/CFTR-1 to
      intrapulmonary airway epithelia of cotton rats and nasal epithelia of Rhesus
      monkeys. In both species we detected CFTR mRNA and protein after repeated
      administration and in monkeys, protein was detected six weeks after repeat
      administration. The vector did not replicate and was rapidly cleared. Despite an
      antibody response, there was no evidence of a local or systemic inflammatory
      response after repeat administration. These data indicate that repetitive
      administration of Ad2/CFTR-1 is both safe and efficacious.

PMID- 7511026
TI  - New code of practice for the control of legionellas in health care premises.

PMID- 7511028
TI  - [Possibilities and limitations of ambulatory cancer therapy].

PMID- 7511029
TI  - The cellular action of antiarrhythmic drugs.

PMID- 7511030
TI  - Antioxidants and atherosclerosis: a molecular perspective.
AB  - Current models of atherogenesis link abnormalities in the oxidative state of the
      vascular wall with interactions with the immune system, leading to a cycle of
      localized inflammatory and growth responses that result in the characteristics of
      the mature atherosclerotic lesion. The oxidative modification of LDL may be an
      important manifestation and mediator of this process, although the degree to
      which this contributes to atherogenesis has not been directly assessed. Another
      important mechanism may involve the linkage of the oxidative state of the
      vascular endothelial cell, through specific transcriptional regulatory factors,
      to control the expression of a gene involved in this disease process. This
      further expands the idea of oxidative stress as an important regulatory signal in
      the pathogenesis of atherosclerosis and provides important paradigms for the
      development of novel therapeutic treatment regimens, drug design, and diagnostic
      assessments of disease state.

PMID- 7511031
TI  - 31P chemical shift as a probe of structural motifs in RNA.

PMID- 7511027
TI  - Correlative retention time peak identification method for glycated haemoglobin in
      high-performance liquid chromatography.
AB  - A convenient peak identification method in stepwise elution was investigated and
      correlation among the retention times of peaks in ion-exchange chromatography of
      glycated haemoglobin was assessed. By using a correlation method, accuracy of
      peak identification among columns with degradation and product deviations can be
      maintained. The correlative retention time identification procedure is treated
      theoretically.

PMID- 7511032
TI  - Assignment strategies and analysis of cross-peak patterns and intensities in the
      three-dimensional homonuclear TOCSY-NOESY of RNA.
AB  - The application of 3D TOCSY-NOESY to the analysis of RNA is presented, using a
      TOCSY-NOESY spectrum of the RNA duplex r(5'GGGCUGAAGCCU'). It is shown that for
      RNA molecules, 3D spectra can be obtained with a digital resolution comparable to
      that obtained for 2D NMR with full spectral information. The improvement in
      assignment over 2D methods is shown and discussed on the basis of an assignment
      strategy presented earlier. A simple and straightforward method for determining
      sugar puckers and gamma backbone torsion angles is presented, which is derived
      from an analysis of cross-peak intensities originating from the TOCSY coherence
      transfer among sugar protons and H5'/5" protons. The stereospecific assignment of
      the H5'/5" resonances in 3D TOCSY-NOESY spectra is also discussed.

PMID- 7511033
TI  - Effects of intrahippocampal colchicine administration on the levels and
      localization of microtubule-associated proteins, tau and MAP2.
AB  - Colchicine, a microtubule disrupting agent, has been used to model several
      aspects of Alzheimer's disease-related neuropathology. The formation of
      neurofibrillary tangles, one of the pathological hallmarks of Alzheimer's
      disease, involves the loss of tau (a low mol. wt. microtubule-associated protein)
      from axons and accumulation of abnormally phosphorylated tau in somatodendritic
      compartments. Other cytoskeletal proteins, such as microtubule-associated protein
      2 (MAP2), disappear as tau accumulates. The present study was directed at
      evaluating the effects of colchicine on tau and MAP2, to determine if changes in
      their levels or distribution might be similar to those which precede the
      formation of neurofibrillary tangles in Alzheimer's disease. Six hours following
      intrahippocampal colchicine injection (3.5 micrograms injected into two rostro
      caudal locations) tau-1 immunostaining was enhanced in CA1 s. radiatum and
      decreased in the outer molecular layer of the dentate gyrus. In addition, a shift
      in the relative abundance of tau isoforms was observed in Western blots. Both the
      immunocytochemical and immunoblot results are consistent with a dephosphorylation
      of tau. Loss of MAP2 was evident 3 days postinjection which coincided with a loss
      of Cresyl violet staining in granule cell, CA3, subicular and entorhinal neurons.
      Accumulation of tau or MAP2 in neuronal perikarya was not observed at any
      postinjection time points. Thus, intrahippocampal colchicine administration does
      not model the shift in tau localization, excessive tau phosphorylation, or other
      cytoskeletal alterations that are suggested to precede or accompany the formation
      of neurofibrillary pathology in Alzheimer's disease.

PMID- 7511034
TI  - Distribution of dopaminergic fibers in the central division of the extended
      amygdala of the rat.
AB  - The distribution of dopaminergic fibers in the principal components of the
      central extended amygdala (central amygdaloid nucleus (Ce), substantia
      innominata, and bed nucleus of the stria terminalis (BNST)), was studied using
      immunocytochemistry against tyrosine hydroxylase, dopamine beta-hydroxylase and
      dopamine. Dopamine fibers were found most densely distributed in the dorsolateral
      subdivision of the BNST and the lateral part of the Ce. Smaller numbers of
      dopaminergic fibers were found in the rest of the central extended amygdala. In
      contrast, dopamine beta-hydroxylase fibers were virtually absent from the
      dorsolateral bed nucleus of the stria terminalis and lateral part of the central
      amygdaloid nucleus, but were distributed in a moderate density in the medial part
      of Ce, dorsal substantia innominata and posterolateral BNST. Our results show
      that dopamine fibers are most concentration over those regions of the central
      extended amygdala with large numbers of GABAergic neurons whose projections
      remain within the central extended amygdala, while noradrenergic fibers are most
      heavily concentrated over those regions containing a large proportion of
      brainstem projection neurons. That dopamine fibers are concentrated over regions
      with GABAergic medium spiny neurons suggests that those regions might be
      organized as a striatal parallel.

PMID- 7511035
TI  - Neuro-glial neurotrophic interaction in the S-100 beta retarded mutant mouse
      (Polydactyly Nagoya). I. Immunocytochemical and neurochemical studies.
AB  - The homozygote of a mouse strain with genetic polydactyly (Polydactyly Nagoya;
      Pdn) shows several brain abnormalities, and significant decrease of S-100 beta in
      the brain. In order to clarify the effects of the retarded production of S-100
      beta on the development of monoaminergic neuronal systems and supporting glial
      cells, immunocytochemical studies of tyrosine hydroxylase (TH), serotonin (5-HT),
      S-100 beta and glial fibrillary acidic protein (GFAP). In addition, high
      performance liquid-chromatography (HPLC) measurements of serotonin and 5
      hydroxyindoleacetic acid (5-HIAA) of homozygote (Pdn/Pdn) mouse were examined,
      and the results were compared with those of other genotypes; heterozygote (Pdn/+)
      and wild type (+/+) mice. In all types of mice, S-100 beta positive cells and
      serotonergic fibers were widely distributed throughout the brains and
      serotonergic cell bodies were located in the brainstem. However, the hippocampus
      and caudo-dorsal cortex of Pdn/Pdn mouse were markedly reduced in S-100 beta
      positive cells and in serotonergic fibers. Furthermore, abnormal distribution of
      GFAP positive cells and fibers were observed in the neocortex and hippocampus of
      Pdn/Pdn brain. No differences were seen in the distribution of TH neurons or
      fibers distribution. In the HPLC study, the content of 5-HT and 5-HIAA of the
      hippocampus and cortex of Pdn/Pdn mouse was lower than those of Pdn/+ and +/+
      mice. The present results suggest that the developmental defect of serotonergic
      fibers in the Pdn mutant mouse is correlate to the deficiency of S-100 beta in
      the astrocyte of this mutant.

PMID- 7511036
TI  - Differential localization of 3H-[Pro9]SP binding sites in the guinea pig and rat
      brain.
AB  - Due to the existence of differences in the pharmacological properties of
      tachykinin NK-1 receptors in the rat and the guinea pig, the autoradiographic
      distribution of NK-1 binding sites was compared in the brain of the two species
      using the selective NK-1 ligand 3H-[Pro9]SP. If a good similarity in the
      distribution of NK-1 binding sites could be seen in basal ganglia, a relative
      absence of correlation was observed between the estimated optical densities in
      other brain structures of the two species. For instance, the interpeduncular
      nucleus, the lateral habenular nucleus and the deep layers of the cerebral cortex
      were labeled in the guinea pig but not in the rat while the reverse was observed
      for the columns of the vermis lobules 9-10, the dorsal raphe nucleus, the medial
      habenular nucleus, the superficial cortical layers and the dorsal hippocampus.
      Furthermore, the high similarity found in the localization of 125I-BHSP (a non
      selective ligand) and 3H-[Pro9]SP binding sites, does not suggest the existence
      of NK-1 binding site subtypes in the guinea pig brain.

PMID- 7511037
TI  - Antinociceptive effect of brain-derived neurotrophic factor and neurotrophin-3.
AB  - Infusions of brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3),
      but not nerve-growth factor, into the rat midbrain significantly elevated the
      tail-flick response latency. Analgesia was observed as soon as 24 h after the
      onset of infusion, reached maximum levels by day 5 and remained constant for at
      least an additional 6 days, suggesting no development of tolerance. BDNF infusion
      also increased latency in the hot-plate test. Naloxone administration reversed
      the BDNF-induced increase in the tail-flick latency. The antinociceptive effect
      of BDNF infusion was accompanied by an augmentation in serotonergic activity
      within the brain and spinal cord. These data demonstrate both an effect of BDNF
      and NT-3 on serotonergic neurons and an analgesic property of these neurotrophins
      which appears to involve both serotonin and opioid mechanisms.

PMID- 7511038
TI  - The origin and composition of peroxidase-positive granules in cysteamine-treated
      astrocytes in culture.
AB  - Gomori astrocytes, which are prominent in periventricular regions of the brain,
      contain inclusions that stain with Gomori dyes, and exhibit an orange-red
      autofluorescence and a non-enzymatic peroxidase activity. Recently, such
      astrocytes have been induced in dispersed glial cultures by exposure to
      cysteamine. Using these cells, we have shown that the peroxidase-positive
      inclusions (Gomori bodies) are multicompartmental, that iron co-localizes with
      the peroxidase activity, and that the iron is often segregated in one of the
      compartments of the body. The goal of the present study was to determine the
      origin and process of formation of these bodies. The results indicate that
      cysteamine induces aberrations in mitochondrial structure associated with the
      acquisition of iron and the associated peroxidase activity. Mitochondria thus
      transformed appear to initiate an autophagic process in which they, and adjacent
      structures, are sequestered. The presence of acid phosphatase activity in a
      number of mature Gomori bodies attests to the participation of lysosomal elements
      in this process. These results indicate, therefore, that the Gomori body is a
      complex autophagosome in which the iron-containing compartments, putatively
      responsible for the peroxidase activity, represent undegraded transformed
      mitochondria.

PMID- 7511039
TI  - Near-diploidy: a new prognostic factor for clinically localized prostate cancer
      treated with external beam radiation therapy.
AB  - BACKGROUND: DNA ploidy is a significant prognostic factor in patients with
      prostate cancer. Using DNA/nuclear protein flow cytometry, a subpopulation of
      tumors with near-diploid DNA is identifiable. The prognostic significance of near
      diploidy was examined. METHODS: Paraffin-embedded formalin fixed prostate tumor
      tissue from patients treated at M. D. Anderson Cancer Center with external beam
      radiation therapy was processed for DNA/nuclear protein flow cytometry. All
      patients had pretreatment and follow-up serum prostate specific antigen (PSA)
      levels. Seventy-six specimens were suitable for flow cytometric analysis. Tumors
      were classified as either diploid (n = 30), near-diploid (n = 24), or nondiploid
      (n = 22, tetraploid and aneuploid). Median follow-up time was 36 months. RESULTS:
      Diploid tumors were associated with a significantly better actuarial outcome at 4
      years, compared with near-diploid tumors, using either biochemical relapse
      (rising PSA) or a composite end point of a rising PSA or clinical relapse (16%
      versus 52% relapse, P < 0.05, log-rank). Moreover, patients who had nondiploid
      tumors had the worst prognosis (77% relapse, composite end point). No significant
      difference was observed between diploid and near-diploid neoplasms regarding
      actuarial local control, freedom from metastasis, freedom from clinical relapse,
      or overall survival time. A Cox proportional hazards model, using the composite
      end point of a rising PSA or relapse, was performed with ploidy categorized as
      diploid, near-diploid, and nondiploid; pretreatment PSA, DNA ploidy, and tumor
      grade were found to be independent prognostic factors. When ploidy was
      categorized as diploid or near-diploid (nondiploid tumors excluded), pretreatment
      serum PSA and DNA ploidy were independent predictors of outcome. Ploidy remained
      an independent prognostic factor even when nondiploid tumors were excluded.
      CONCLUSIONS: These data show that patients who have near-diploid tumors have an
      intermediate prognosis between the more favorable diploid tumors and the less
      favorable nondiploid tumors.

PMID- 7511040
TI  - The T classification of clinically localized prostate cancer. An appraisal based
      on disease outcome after radiation therapy.
AB  - BACKGROUND: This study was performed to evaluate the use of the 1992
      International Union Against Cancer (UICC)/American Joint Committee on Cancer
      (AJCC) T categories for localized prostate cancer treated with radiation therapy
      and to compare the prognostic power of this system with the Whitmore-Jewett
      scheme. METHODS: The outcome for 427 men with Stages A2-C or T1a-T4b prostate
      cancers, followed for a mean of 32 months after treatment, was evaluated for
      relapse or rising prostate-specific antigen (PSA) levels, disease relapse,
      metastatic failure, and local recurrence relative to the two staging systems.
      Univariate and multivariate analysis was used to compare the two staging systems.
      The T categories were based on digital rectal examination. RESULTS: At 5 years,
      the actuarial incidence of relapse or rising PSA level was as follows: Stage A2,
      29%; Stage B, 41%; Stage C, 62%. The corresponding results according to T
      category were as follows: T1a, 0%; T1b, 37%; T1c, 23%; T2a, 39%; T2b, 38%; T2c,
      42%; T3a, 53%; T3c, 68%; T4b, greater than 75%. Too few patients were in the T3b
      and T4a categories. The following five-category grouping was significantly
      superior prognostically to the Whitmore-Jewett system: T1a, T1c, T1b/T2, T3, T4.
      The actuarial incidences of relapse or rising PSA at 5 years were as follows:
      T1a, 0%; T1c, 23%; T1b/T2, 41%; T3, 61%; and T4, 75%. No differences were evident
      within the T2 or T3 categories. CONCLUSIONS: The current UICC/AJCC system appears
      to be a valid method for categorizing a primary prostate carcinoma. This system
      defines a greater number of meaningful tumor categories and is prognostically
      superior to the traditional Whitmore-Jewett scheme.

PMID- 7511041
TI  - Hepatoid adenocarcinoma in the urinary bladder. Unusual localization of a newly
      recognized tumor type.
AB  - A tumor mass resected from the anterior bladder wall of a 68-year-old woman
      displayed unusual histologic features: sheets of hepatoid cells merging focally
      with a secondary glandular pattern of adenocarcinoma. Intracytoplasmic hyaline
      globules and bile production within the solid areas supported the impression of
      hepatocytic differentiation. Immunoreactivity for alpha-fetoprotein (AFP) and
      alpha-1-antitrypsin and a striking canalicular immunostaining pattern for
      carcinoembryonic antigen and epithelial membrane antigen all indicate
      hepatocellular differentiation within this bladder tumor. This represents a case
      of a hepatoid adenocarcinoma located in the urinary bladder. The use of the term
      "hepatoid" in the literature is reviewed and the reported cases are grouped into
      two distinct categories of tumors: (1) germ cell tumors with focal hepatoid areas
      and (2) true hepatoid adenocarcinomas that meet histologic and
      immunohistochemical criteria for hepatocellular differentiation. AFP-producing
      tumors without any other feature of hepatocellular differentiation should not be
      considered as hepatoid tumors. This classification of hepatoid tumors is likely
      to be important in elucidating the histogenesis and clinicopathologic features of
      these unusual neoplasms.

PMID- 7511042
TI  - Double-cycle high-dose chemotherapy with peripheral blood stem cells and
      hematopoietic growth factor support in patients with advanced solid tumor. A
      pilot study by the Hong Kong Biotherapy Group.
AB  - BACKGROUND: High-dose chemotherapy with autologous bone marrow transplantation
      has been useful in some patients with advanced breast, lymphoma, or germ cell
      tumors. Double-cycle high-dose chemotherapy may be able to deliver an even higher
      total dose within a given time period. It is important to determine whether
      peripheral blood stem cells and hematopoietic growth factors can diminish the
      hematopoietic toxicity of such a treatment. METHODS: From November 1989 to May
      1991, 14 patients were enrolled in two cycles of high-dose chemotherapy
      consisting of cyclophosphamide, 4.5 g/m2; cisplatin, 150 mg/m2; and etoposide,
      900 mg/m2 in each cycle. The first five patients received peripheral blood stem
      cells harvested from 8-10 leukaphereses during steady state. The next nine
      patients, besides receiving peripheral blood stem cells mobilized by growth
      factors, also received either granulocyte-macrophage colony-stimulating factor
      (GM-CSF) at 250 micrograms/m2/day by two subcutaneous (s.c.) injections given 12
      hours apart from day 6 until neutrophil recovery or granulocyte colony
      stimulating factor (G-CSF) at 200 micrograms/m2 as daily s.c. injections.
      RESULTS: For the first five patients, there was a median of 14 days from the
      first day of absolute marrow suppression to neutrophil count exceeding
      500/microliters and a median of 15 days for a platelet count exceeding
      20,000/microliters. For the next nine patients, with the use of either G-CSF or
      GM-CSF, there was a median of 8 days for a neutrophil count exceeding
      500/microliters and and a median of 11 days for a platelet count exceeding
      20,000/microliters. CONCLUSION: With the use of peripheral stem cells and growth
      factors, high-dose chemotherapy could be given safely every 30 days with
      acceptable toxicity. A high complete response rate was seen in patients with
      nasopharyngeal carcinoma and in patients with small cell and non-small cell lung
      cancer who either had not received previous chemotherapy or who had responded to
      previous chemotherapy.

PMID- 7511043
TI  - MDR1 gene-specific monoclonal antibody C494 cross-reacts with pyruvate
      carboxylase.
AB  - Overexpression of P-glycoprotein, the plasma membrane protein product of the MDR1
      gene, is a major determinant in the development of resistance to a large number
      of cancer chemotherapeutic agents. A battery of antibodies, including the MDR1
      gene-specific monoclonal antibody (mAb) C494, is used to evaluate human tissues
      in clinical multidrug resistance surveillance and modulation trials. In rat liver
      fractions, we report that mAb C494 strongly cross-reacted with a nonmembranous
      M(r) approximately 130,000 protein, comigrating with core-glycosylated human MDR1
      on 7% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. By
      immunoblotting and microsequence analysis, this protein was identified as
      pyruvate carboxylase (PC), an abundant mitochondrial enzyme. A search of the
      National Center for Biotechnology Information data base, using the epitope
      specific sequence of mAb C494, revealed that PC (mouse) contains four of the five
      most reactive amino acids (TLEG), located near the COOH-terminal end of PC at
      positions 1167-1170. mAb C494 specifically reacted with PC purified from bovine
      liver; immunoreactivity was completely abolished by preincubating mAb C494 in the
      presence of excess synthetic C494 epitope-specific peptide. Furthermore, in
      cryosections of human skeletal muscle, a tissue known not to express P
      glycoprotein, peptide-displaceable immunohistochemical staining with mAb C494
      showed a distinct mitochondrial pattern specific to type 1 fibers. Variable
      immunostaining results were obtained with formaldehyde-fixed, paraffin-embedded
      muscle and isolated liver mitochondrial preparations. In summary, mAb C494 cross
      reacted strongly with rat, bovine, and human PC. Caution is warranted in
      interpretation of immunoblots and immunohistochemical sections with this putative
      MDR1 gene-specific mAb.

PMID- 7511044
TI  - Inhibition of human melanoma growth and metastasis in vivo by anti-CD44
      monoclonal antibody.
AB  - CD44 is a M(r) 90,000 surface glycoprotein believed to be involved in cell
      adhesion and migration. We investigated the role of CD44 in tumor growth and
      metastasis using human melanoma cell lines SMMU-1 and SMMU-2. Both SMMU-1 and
      SMMU-2 form tumors in the s.c. tissues when injected s.c. in SCID mice but only
      SMMU-2 metastasizes. Approximately one-half of SCID mice receiving injections of
      SMMU-2 s.c. develop metastatic tumors. SMMU-2 but not SMMU-1 expresses high
      levels of the hematopoietic form of CD44 and binds fluorescence-conjugated
      hyaluronic acid in vitro. GKW.A2 is a monoclonal antibody specific for human CD44
      that can completely inhibit the binding of hyaluronic acid to SMMU-2 tumor cells
      in vitro. Moreover, in vivo injection of GKW.A3 inhibited the growth and
      metastatic potential of SMMU-2 tumor cells. Administration of GKW.A3 i.v. 1 week
      after s.c. tumor injection did not inhibit local tumor development but inhibited
      the formation of metastatic tumors and prolonged animal survival. Therefore,
      interactions between CD44 on tumor cells and its ligands in vivo may be necessary
      for tumor growth and metastasis.

PMID- 7511045
TI  - Increased androgen receptor activity and altered c-myc expression in prostate
      cancer cells after long-term androgen deprivation.
AB  - Proliferation of LNCaP 104-S cells, a clonal subline of the human prostate cancer
      cell line, was very slow in androgen-depleted medium but increased 10-13-fold in
      the presence of 0.1 nM of a synthetic androgen, R1881. This induction of
      proliferation was diminished at higher concentrations of R1881, indicating the
      biphasic nature of the androgen effect. After 20-30 passages in androgen-depleted
      medium, these cells progressed to 104-I cells, which exhibited much lower
      proliferative sensitivity to 0.1 nM R1881. After another 20-30 passages, LNCaP
      104-I cells gave rise to 104-R cells, which proliferated rapidly without
      additional androgen. Proliferation of 104-R cells was induced 2-fold by 0.01 nM
      R1881 but was repressed by 0.1 nM R1881 and above. Thus, androgen induction and
      repression of proliferation could be seen at lower concentrations of androgen as
      the cells progressed. During the transition of 104-S cells to 104-R cells, the
      androgen receptor mRNA level increased 2.5-fold whereas the androgen receptor
      protein level increased 15-fold in the absence of androgen. Androgen receptor
      transcriptional activity, measured by androgen induction of prostate-specific
      antigen mRNA and chloramphenicol acetyltransferase activity in transfected cells,
      increased up to 20-fold during the progression. LNCaP cells, therefore, appear to
      be able to adapt to reduced androgen availability by increasing their sensitivity
      to androgen, raising questions concerning the therapeutic strategies used against
      prostate cancer. Androgen induction of c-myc expression in 104-R cells occurred
      at a 10-fold lower concentration (0.01 nM) than in 104-S cells (0.1 nM). In all
      stages, cell proliferation and c-myc expression were repressed by androgen at a
      high concentration (20 nM), but the repression of cell proliferation was blocked
      by retroviral overexpression of c-myc.

PMID- 7511046
TI  - Endogenous 12(S)-HETE production by tumor cells and its role in metastasis.
AB  - 12(S)-Hydroxyeicosatetraenoic acid [12(S)-HETE] is the 12-lipoxygenase metabolite
      of arachidonic acid. Previously, we have demonstrated that exogenous 12(S)-HETE
      can activate protein kinase C, increase cell surface expression of integrins,
      enhance adhesion, induce endothelial cell retraction, and increase experimental
      metastasis of tumor cells. Because of these prominent effects of exogenous 12(S)
      HETE on tumor cell metastatic potential, it is important to determine whether
      there is endogenous 12(S)-HETE production by tumor cells. In the present study,
      mRNAs from human, rat, and mouse platelets as well as human colon carcinoma
      (Clone A), rat Walker carcinoma (W256), and mouse melanoma (B16a) and lung
      carcinoma (3LL) were reverse transcribed and amplified by polymerase chain
      reaction with platelet 12-lipoxygenase specific primers. Identity of the
      polymerase chain reaction fragments was confirmed by sequencing. 12-Lipoxygenase
      protein was detected by Western blotting. Tumor cell-derived 12-HETE was
      determined by reverse phase-high performance liquid chromatography analysis. In
      addition, the effect of endogenous 12(S)-HETE on tumor cells was studied by using
      a platelet-type 12-lipoxygenase selective inhibitor (N-benzyl-N-hydroxy-5
      phenylpentanamide). Our results suggest that some tumor cells express platelet
      type 12-lipoxygenase mRNA, protein and metabolize arachidonic acid to 12(S)-HETE
      and that endogenous 12(S)-HETE, like the exogenous 12(S)-HETE, may play an
      important role in tumor cell adhesion to matrix in vitro and lung colonization in
      vivo.

PMID- 7511047
TI  - Anti-Fas on nonhematopoietic tumors: levels of Fas/APO-1 and bcl-2 are not
      predictive of biological responsiveness.
AB  - Fas/APO-1 is a cell surface protein known to trigger apoptosis in a variety of
      cell types upon specific antibody binding. Although extensively studied on normal
      and malignant hematopoietic cells, little is known about Fas/APO-1 on
      nonhematopoietic cells. In the study presented here, we have examined Fas/APO-1
      expression and function on 11 human tumors of nonhematopoietic origin. By flow
      cytometric analysis, Fas/APO-1 was expressed on 10 of the 11 tumors at levels
      comparable to those previously reported for lymphoid cells sensitive to the
      cytolytic effects of anti-Fas. Despite abundant cell surface expression, only 4
      of the 10 Fas-positive tumors were sensitive to the cell-killing effects of anti
      Fas. Moreover, anti-Fas enhanced the growth of 2 of 10 Fas-positive tumors.
      Additional studies using cycloheximide demonstrated that de novo protein
      synthesis was required for anti-Fas-triggered growth stimulation and, at least in
      one case, was responsible for the resistance to antibody-induced apoptosis. The
      biological effects initiated by anti-Fas engagement, however, were not correlated
      with endogenous bcl-2 expression. This report documents that: (a) Fas/APO-1 is
      widely expressed on cultured nonhematopoietic tumors; (b) the inherent
      susceptibility to anti-Fas-induced apoptosis is not correlated with expression of
      the Fas/APO-1 protein; (c) Fas/APO-1 engagement can result in growth enhancement;
      and (d) protective/growth-promoting proteins other than bcl-2 may contribute to
      the diverse spectrum of biological effects induced by anti-Fas engagement of the
      Fas/APO-1 protein.

PMID- 7511048
TI  - Induction of apoptotic DNA fragmentation and cell death in HL-60 human
      promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C.
AB  - The present studies were undertaken to characterize further the potential role of
      protein kinase C (PKC) in the regulation of apoptosis in HL-60 promyelocytic
      leukemia cells. The capacity of acute exposure to specific and nonspecific
      pharmacological inhibitors of PKC to promote apoptotic DNA fragmentation was
      examined both quantitatively and qualitatively and correlated with effects on
      cellular differentiation and proliferation. Incubation of HL-60 cells for 6 h
      with chelerythrine and calphostin C (highly specific inhibitors that act at the
      regulatory domain) or H7 and gossypol (nonspecific inhibitors that act at the PKC
      catalytic domain) produced concentration-dependent increases in DNA
      fragmentation. Induction of DNA fragmentation by chelerythrine, calphostin C, and
      gossypol was biphasic, resulting in a sharp decline in effect at concentrations
      above 5 microM, 0.1 microM, and 100 microM, respectively, whereas maximal and
      more stable effects were observed in response to H7 (100 microM). A 6-h exposure
      to staurosporine, a nonspecific but potent PKC inhibitor, failed to induce DNA
      fragmentation at concentrations generally used to achieve maximal inhibition of
      enzyme activity (e.g., 50 nM) but promoted fragmentation at considerably higher
      concentrations (e.g., > or = 200 nM). In contrast, 6-h exposures to the
      nonspecific protein kinase inhibitor hypericin (0.1 to 100 microM) or to the
      nonspecific inhibitor of protein kinase A, HA1004 (50 microM), were without
      effect on DNA fragmentation. DNA obtained from cells exposed to chelerythrine (5
      microM), calphostin C (100 nM), H7 (50 microM), gossypol (50 microM), and
      staurosporine (200 nM)--but not hypericin (25 microM)--exhibited clear evidence
      of internucleosomal DNA cleavage on agarose gel electrophoresis; moreover, these
      cells exhibited the classical morphological features of apoptosis (cell
      shrinkage, nuclear condensation, and the formation of apoptotic bodies). All of
      the PKC inhibitors that induced apoptosis, and one of the inhibitors that did not
      (hypericin), substantially inhibited HL-60 cell clonogenicity at the
      concentrations evaluated. None of the agents tested induced cellular maturation
      as assessed by nonspecific esterase and nitro-blue tetrazolium positivity. DNA
      fragments obtained from cells exposed to specific and nonspecific PKC inhibitors
      possessed predominantly 5'-phosphate termini, consistent with the action of a
      Ca(2+)-/Mg(2+)-dependent endonuclease. Finally, Northern blot analysis revealed
      that exposure to calphostin C at a concentration that induced apoptosis (100 nM)
      failed to alter expression of bcl-2, an oncogene known to block apoptosis in both
      lymphoid and myeloid leukemia cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7511049
TI  - Covalent coupling of methotrexate to dextran enhances the penetration of
      cytotoxicity into a tissue-like matrix.
AB  - For antitumor agents introduced directly into the intracranial space, the extent
      of penetration into tissue, and hence the effectiveness of therapy, depends on
      the rate of drug elimination from the tissue. To test the hypothesis that slowly
      eliminated agents would penetrate further through tissues, methotrexate (MTX)
      dextran conjugates were produced by covalently linking MTX to dextran through a
      short-lived ester bond (MTX-ester-dextran; t1/2 approximately 3 days in buffered
      saline) and a longer-lived amide bond (MTX-amide-dextran; t1/2 > 20 days in
      buffered saline). The ability of these agents to kill cells and to penetrate
      through tissue was evaluated using: (a) human brain tumor (H80) cells in a
      standard format; (b) H80 cells in a novel three-dimensional format that mimics
      many characteristics of intracranial tumors; and (c) 9L gliosarcoma in the rat
      brain. Penetration into three-dimensional tissue-like matrices was performed by
      suspending H80 cells in agarose gels within a hollow fiber that was permeable to
      MTX but not dextran and injecting MTX or MTX-dextran conjugates into one end of
      the fiber. The cytotoxicity of MTX-ester-dextran and MTX-amide-dextran against
      H80 was equivalent to unmodified MTX (50% inhibitory concentration, approximately
      0.01 microgram/ml). When released from a biodegradable polyanhydride polymer
      matrix, MTX and MTX-dextran conjugates retained their ability to inhibit
      dihydrofolate reductase activity. When MTX or MTX-dextran was diffused into the
      three-dimensional tumor cell matrix for 10 days, cytotoxic activity penetrated >
      2 cm for MTX-amide-dextran and approximately 1 cm for MTX or MTX-ester-dextran;
      this enhanced penetration correlated with the stability of the MTX-dextran
      linkage. Intracranial polymeric delivery of MTX or MTX-amide-dextran to rats with
      intracranial 9L gliosarcoma produced modest but significant increases in
      survival; conjugation of MTX to dextran appeared to shift the dose-response curve
      to a lower dosage.

PMID- 7511050
TI  - Retinoic acid-induced expression of CD38 antigen in myeloid cells is mediated
      through retinoic acid receptor-alpha.
AB  - CD38 is a leukocyte differentiation antigen that has been thought to be a
      phenotypic marker of different subpopulations of T- and B-lymphocytes. In myeloid
      cells, CD38 is expressed during early stages of differentiation. Virtually no
      information is available on regulation and functions of CD38. Recently we
      reported that all-trans-retinoic acid (ATRA) is a potent and highly specific
      inducer of CD38 expression in human promyelocytic leukemia cells. Here we report
      that ATRA-induced expression of CD38 antigen in myeloid cells is mediated through
      retinoic acid-alpha receptor (RAR alpha). ATRA failed to induce CD38 expression
      in a mutant subclone of the HL-60 myeloid leukemia cell line (designated HL-60R)
      that is relatively resistant to ATRA-induced granulocytic differentiation.
      Retroviral vector-mediated transduction of RA receptor (RAR alpha) into this HL
      60R subclone completely restored the sensitivity of these cells to ATRA in terms
      of their ability to express CD38. In contrast, CD38 expression was not inducible
      by ATRA in HL-60R cells, transfected with a functional RAR beta, RAR gamma, or
      RXR alpha receptor. Induction of CD38 in acute promyelocytic and acute
      myeloblastic leukemia cells was independent of ATRA-induced cytodifferentiation.
      Following culture with ATRA, increased CD38 protein levels were also observed in
      normal CD34+ bone marrow cells, but not on normal circulating granulocytes. From
      these results, we conclude that CD38 is ATRA inducible in myeloid leukemia cells
      and normal CD34+ bone marrow cells. This effect is independent of differentiation
      and is mediated by RAR alpha in HL-60 cells, suggesting a similar role for RAR
      alpha in CD38 expression in other hematopoietic cells.

PMID- 7511051
TI  - Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent
      5-aza-2'-deoxycytidine.
AB  - MAGE-1 is a gene that encodes an antigen on a melanoma cell line that is
      recognized by cytolytic T-cells. We have used a reverse transcription-polymerase
      chain reaction assay to analyze expression of the MAGE-1 gene by cell lines from
      different types of tumors, melanomas from different stages of disease
      progression, normal diploid cell lines, and melanocyte and nevus tissue from
      which malignant melanomas are derived. MAGE-1 is expressed by melanoma tissue
      from all stages of disease, but not melanocytes, nevus tissue, or any normal
      diploid cell line tested. A fraction of tumor lines derived from various
      epithelial and neuroectodermal malignancies expressed MAGE-1 but not peripheral
      blood cells from patients with melanoma. 5-Aza-2'-deoxycytidine (DAC), a
      demethylating agent, was capable of inducing MAGE-1 expression by a MAGE-1
      negative melanoma cell line 888-mel as well as by a number of other melanoma cell
      lines. At an optimum concentration of 1 microM DAC, MAGE-1 expression was
      detectable by 24 h, plateaued by 72 h, but remained high for two weeks after
      removal of DAC from treated 888-mel cells, consistent with induction by
      demethylation. With the exception of tumor-infiltrating leukocytes, no normal
      diploid cell line could be induced with DAC to upregulate MAGE-1 expression. DAC
      treated 888-mel cells were lysed by a MAGE-1-specific major histocompatibility
      complex restricted cytolytic T-cell clone, whereas control untreated cells were
      not, suggesting that production of the antigen encoded by the MAGE-1 gene was
      induced by DAC and that it was presented in association with major
      histocompatibility complex class I molecules at the cell surface for T-cell
      recognition.

PMID- 7511053
TI  - Expression of the prostate-specific membrane antigen.
AB  - We have recently cloned a 2.65-kilobase complementary DNA (cDNA) encoding the
      prostate-specific membrane antigen (PSM) recognized by the 7E11-C5.3 anti
      prostate monoclonal antibody. Immunohistochemical analysis of the LNCaP, DU-145,
      and PC-3 prostate cancer cell lines for PSM expression using the 7E11-C5.3
      antibody reveals intense staining in the LNCaP cells with no detectable
      expression in both the DU-145 and PC-3 cells. Coupled in vitro
      transcription/translation of the 2.65-kilobase full-length PSM cDNA yields an
      M(r) 84,000 protein corresponding to the predicted polypeptide molecular weight
      of PSM. Posttranslational modification of this protein with pancreatic canine
      microsomes yields the expected M(r) 100,000 PSM antigen. Following transfection
      of PC-3 cells with the full-length PSM cDNA in a eukaryotic expression vector, we
      detect expression of the PSM glycoprotein by Western analysis using the 7E11-C5.3
      monoclonal antibody. Ribonuclease protection analysis demonstrates that the
      expression of PSM mRNA is almost entirely prostate specific in human tissues. PSM
      expression appears to be highest in hormone-deprived states and is hormonally
      modulated by steroids, with 5-alpha-dihydrotestosterone down-regulating PSM
      expression in the human prostate cancer cell line LNCaP by 8-10-fold,
      testosterone down-regulating PSM by 3-4-fold, and corticosteroids showing no
      significant effect. Normal and malignant prostatic tissues consistently show high
      PSM expression, whereas we have noted heterogeneous, and at times absent,
      expression of PSM in benign prostatic hyperplasia. LNCaP tumors implanted and
      grown both orthotopically and s.c. in nude mice abundantly express PSM, providing
      an excellent in vivo model system to study the regulation and modulation of PSM
      expression.

PMID- 7511054
TI  - New monoclonal antibodies against the putative immunosuppressive site of
      retroviral p15E.
AB  - Both retroviral infections as well as human tumors may cause immunosuppression.
      One of the factors involved in immunosuppression in patients with squamous cell
      carcinoma of the head and neck (SCC-HN) is a protein related to the retroviral
      protein p15E. A conserved, 17-amino acid sequence represents the
      immunosuppressive epitope of retroviral p15E. In order to study the relationship
      between SCC-HN associated immunosuppression and retroviral p15E, we produced
      three new monoclonal antibodies (MAbs; ER-IS1, ER-IS2, and ER-IS5) directed
      against the immunosuppressive synthetic CKS-17 peptide. These MAbs react with the
      immunosuppressive peptide (in enzyme-linked immunosorbent assay), with human
      tumor cell lines (in FACScan analysis), with retroviral p15E (on Western blot),
      and with cryostat sections of SCC-HN tumor tissue. In addition, the MAbs
      neutralize the immunosuppressive low molecular weight factors present in sera of
      patients with SCC-HN. These results show that retroviral p15E and the
      immunosuppressive factors associated with SCC-HN share a conserved
      immunosuppressive epitope and that MAbs against this epitope can be used for
      detection and neutralization of the tumor-associated immunosuppressive
      protein(s).

PMID- 7511052
TI  - Mutation analysis of the THRA1 gene in breast cancer: deletion/fusion of the gene
      to a novel sequence on 17q in the BT474 cell line.
AB  - We have previously described a common region of deletion and allele loss on
      chromosome 17q in sporadic breast cancers that is likely to contain a tumor
      suppressor gene. The region, mapped to 17q12-q21, was bordered by D17S250 and
      D17S579 on the centromeric and telomeric sides, respectively. This deletion
      region overlaps the BRCA1 locus, which predisposes to familial breast and ovarian
      cancer. The most frequent loss of heterozygosity was observed at the thyroid
      hormone receptor alpha (THRA1) locus. Southern analysis revealed a rearrangement
      of THRA1 in the BT474 breast cancer cell line. This rearrangement represented a
      deletion of exons 8-10 of one THRA1 allele that was also coamplified with ERBB2.
      Northern blots showed two mutant transcripts in BT474 cells. Analysis of the
      mutant transcripts revealed fusion of the THRA1 exon 7 by splicing to a novel
      sequence designated BTR for "BT474 transcribed rearrangement." BTR was found to
      be highly conserved and mapped to 17q. The deletion in BT474 cells spans the
      entire BRCA1 region. To search for additional mutations in the THRA1 gene, all
      nine protein-encoding exons of THRA1 were examined for point mutations via single
      strand conformation analysis in a series of primary breast tumors, breast cancer
      cell lines, and lymphoblastoid cell lines derived from the youngest affected
      members of several German breast cancer families. No point mutations were
      detected, including the unrearranged THRA1 allele in BT474. We have thus excluded
      THRA1 as a commonly mutated sporadic breast cancer tumor suppressor gene and as
      the BRCA1 gene.

PMID- 7511056
TI  - [The effect of amino acids, sugars and fats on activation of pancreatic enzymes].
AB  - BACKGROUND: Investigations of pancreatic enzymes have again become a topic.
      Attention concentrates rather on exogenous activators. The objective of the
      present work was to assess to what extent some amino acids, sugars and fats
      affect the activity of pancreatic enzymes "in vitro". METHODS AND RESULTS: The
      author compared the degree of hydrolysis of enzyme-substrate with the degree of
      hydrolysis enzyme-substrate-activator. Twenty-four amino acids, 25 sugars and 7
      fats were analyzed. Of the 24 tested amino acids only six activate amylase:
      cysteine 39.9 x, histidine 21 x, lysine 3.8 x, methionine 3.3 x, tryptophan 2.9 x
      and tyrosine 1.5 x. As compared with control groups, the differences are
      significant, p < 0.01 with the exception of tyrosine (p > 0.05). All amino acids
      activate lipase: serine 3.4 x, aspartic acid 3.1 x, asparagine 3.0 x,
      hydroxyproline 2.7 x alanine 1.1 x (p > 0.05). Of the investigated sugars none
      activated amylase, 14 do not activate picase. Fructose activates lipase 1.9 x,
      inosine 1.8 x, laevulose 1.7 x, maltose 1.6 x, sucrose 1.3 x, xylitol 1.2 x,
      sorbitol 1.1 x, glucosamine 2.6 x and galactosamine 2.0 x. Pure fats do not
      activate pancreatic enzymes. Butter causes a rise of trypsin activity by 1.3 x,
      lard of lipase activity 2 x and trypsin 6.2 x. CONCLUSIONS: In in vitro
      experiments evidence was provided that cysteine, histidine lysine and methionine
      tryptophan and tyrosine activate amylase, all 24 tested amino acids activate
      lipase as well as trypsin to a varying extent. The investigated sugars do not
      activate amylase at all; lipase is activated by 10 sugars and trypsin by four
      sugars. Pure fats do not activate any pancreatic enzymes.

PMID- 7511055
TI  - Growth suppression and toxicity induced by caffeic acid phenethyl ester (CAPE) in
      type 5 adenovirus-transformed rat embryo cells correlate directly with
      transformation progression.
AB  - The active component of the honeybee hive product propolis, caffeic acid
      phenethyl ester (CAPE), induces a selective growth suppressive and toxic effect
      toward cloned rat embryo fibroblast cells transformed by adenovirus type 5 (Ad5)
      or the Ad5 E1A transforming gene versus untransformed cloned rat embryo
      fibroblast cells (Z-z. Su et al., Mol. Carcinog., 4: 231-242, 1991). The present
      study was conducted to determine whether CAPE-induced growth suppression/toxicity
      was a direct result of expression of the Ad5 E1A and E1B transforming genes or a
      consequence of the action of these genes resulting in the transformed state. For
      this investigation we used somatic cell hybrids and 5-azacytidine-treated Ad5
      transformed rat embryo cells that display different stages of expression of the
      transformed phenotype. This series of cell lines has permitted us to determine
      whether expression of the transformed state and the stage of transformation
      progression regulates CAPE sensitivity. Evidence is presented indicating that
      sensitivity to CAPE is directly determined by the state of expression of the
      transformed progression phenotype, as opposed to simply the expression of the Ad5
      E1A and E1B transforming genes. These results provide further evidence that CAPE
      may represent a unique compound that can specifically target progressed
      transformed cells for growth suppression and toxicity. An understanding of the
      mechanism underlying this selective effect of CAPE could result in the
      identification of important biochemical pathways mediating cellular
      transformation and progression of the transformed state.

PMID- 7511057
TI  - Retinohypothalamic projections and immunocytochemical analysis of the
      suprachiasmatic region of the desert iguana Dipsosaurus dorsalis.
AB  - Two separate and distinct retinal projections to the hypothalamus in the iguanid
      lizard Dipsosaurus dorsalis were described using horseradish peroxidase and
      cobalt-filling techniques. Both of the projections were unilateral and completely
      crossed; one terminated in the supraoptic nucleus and the other in the
      suprachiasmatic nucleus. Immunocytochemical analysis showed that the supraoptic
      nucleus contained cell bodies and fibers that cross-react with antibodies raised
      against arginine vasopressin, while the suprachiasmatic nucleus contained
      arginine vasopressin-like immunoreactive fibers emanating from cells in the
      nearby paraventricular nucleus. The suprachiasmatic nucleus contained a dense
      plexus of fibers that cross-reacted with neuropeptide-Y antibody. Antiserum
      against vasoactive intestinal polypeptide showed no reactivity in any part of the
      forebrain, while antiserum against serotonin showed sparse and uniform reactivity
      throughout the forebrain, including the suprachiasmatic nucleus. These results,
      together with other data, indicate that the suprachiasmatic nucleus of D.
      dorsalis is homologous to the suprachiasmatic nuclei of rodents, structures known
      to contain circadian pacemakers. We suggest that the suprachiasmatic nucleus may
      play a similar role in the circadian system of D. dorsalis.

PMID- 7511058
TI  - Transformation and immortalization of Leydig cells from the Sprague-Dawley rat by
      an early genetic region of simian virus 40 DNA.
AB  - Two transformed cell lines of rat Leydig cells were established by transfection
      of primary cells with the transforming region of simian virus (SV40) DNA. Normal
      adult Leydig cells are non-proliferating cells and cease to grow after the first
      trypsinization for cell culturing. The cell lines, NWL2 and NWL15, continued to
      proliferate and subsequently needed subculturing every 2 weeks (split ratio 1:2).
      No crisis was observed after 35 passages for 18 months. Nile red staining showed
      the presence of lipid droplets in both normal and transformed cells, although the
      transformed cells had 2-3-fold higher amounts than the normal cells. The
      integration of T-antigen DNA has taken place in at least 2 and 1 sites in NWL2
      and NWL15, respectively. Both cell lines expressed T-antigen mRNA. The cell lines
      expressed luteinizing hormone receptor (LH-R) (a Leydig cell-specific gene),
      insulin-like growth factor-I, insulin-like growth factor-I receptor (IGF-I-R) and
      insulin-like growth factor binding protein-2 (IGFBP-2) genes. The amounts of
      transcripts of LH-R were lower in the transformed cells as compared to the normal
      cells. The IGF-I-R mRNA levels were comparable to those of the normal Leydig
      cells. NWL2 and NWL15 cells also expressed IGF-I mRNA although to a lesser extent
      than the normal Leydig cells. IGFBP-2 mRNA levels were much higher in both the
      transformed cell lines than in the normal Leydig cells. The transformed cells
      were evaluated for the expression of P450scc, which catalyzes the conversion of
      cholesterol to pregnenolone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511060
TI  - [Seroepidemiological study on hepatitis C virus infection among blood donors from
      various regions in China].
AB  - A total of 2,273 blood donors from various regions in China were tested for serum
      anti-HCV antibodies in a seroepidemiological study. The prevalence of anti-HCV in
      Volunteer blood donors was 0-1.10%, which was lower than that in professional
      blood donors from Liaoning and Anhui Provinces (1.49% and 3.14%, respectively),
      whereas the positivity rate of anti-HCV was as high as 30.13% in the professional
      blood donors from Hebei Province and 31.86% in those from Inner Mongolia
      Autonomous Region. The prevalence of anti-HCV was significantly higher in the
      blood donors with history of hepatitis and abnormal ALT levels than those without
      hepatitis and with normal ALT. Plasma donation was the main cause of HCV
      infection. However, the prevalence of anti-HCV showed no significant sex and age
      differences even though the anti-HCV activity profile showed geographic
      difference.

PMID- 7511059
TI  - Localization of nitric oxide synthase in canine ileocolonic and pyloric
      sphincters.
AB  - The distribution of neurons containing NAD-PH-diaphorase (NADPH-d) activity and
      nitric oxide synthase-like immunoreactivity (NOS-LI) in the canine pyloric and
      ileocolonic sphincters was studied. Cells within the myenteric and submucosal
      ganglia were positive for NADPH-d. These cells generally had the morphology of
      Dogiel type-I enteric neurons, however, there was some diversity in the
      morphology of NADPH-d-positive neurons in the myenteric plexus of the pylorus.
      Intramuscular ganglia were observed in both sphincters, and NADPH-d was found in
      a sub-population of neurons within these ganglia. Dual staining with an antiserum
      raised against nitric oxide synthase (NOS) demonstrated that almost all cells
      with NOS-LI were also NADPH-d positive. Varicose fibers within ganglia and within
      the circular and longitudinal muscle layers also possed NOS-LI and NADPH-d
      activity. Dual staining with anti-VIP antibodies showed that some of the NADPH-d
      positive cells in the myenteric and submucosal ganglia also contained VIP-LI, but
      all VIP-LI-positive cells did not express NADPH-d activity. These data are
      consistent with recent physiological studies suggesting that nitric oxide serves
      as an inhibitory neurotransmitter in the pyloric and ileocolonic sphincters. The
      data also suggest that VIP is expressed in a sub-population of NADPH-d-positive
      neurons and may therefore act as a co-transmitter in enteric inhibitory
      neurotransmission to these specialized muscular regions.

PMID- 7511061
TI  - Dual mode of signal transduction by externally added acidic fibroblast growth
      factor.
AB  - Acidic fibroblast growth factor (aFGF), fused to diphtheria toxin and
      translocated into cells, stimulated DNA synthesis in toxin-resistant cells
      lacking functional aFGF receptors while having a high number of diphtheria toxin
      receptors. In NIH 3T3 cells that lack diphtheria toxin receptors, but have
      receptors for aFGF, both aFGF and the fusion protein induced tyrosine
      phosphorylation, but only aFGF as such entered the nuclei and stimulated DNA
      synthesis. The results indicate that signaling occurs partly through cell surface
      receptors and partly by transport of the growth factor into the cell.

PMID- 7511062
TI  - The amino-terminal portion of CFTR forms a regulated Cl- channel.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel
      consists of two motifs (each containing a membrane-spanning domain [MSD] and a
      nucleotide-binding domain [NBD]) linked by an R domain. We tested the hypothesis
      that one MSD-NBD motif could form a Cl- channel. The amino-terminal portion of
      CFTR (D836X, which contains MSD1, NBD1, and the R domain) formed Cl- channels
      with conductive properties identical to those of CFTR. However, channel
      regulation differed. Although phosphorylation increased activity, channels opened
      without phosphorylation. MgATP stimulated D836X more potently than CFTR and may
      interact at more than one site. These data and migration of D836X on sucrose
      density gradients suggest that D836X may function as a multimer. Thus, the amino
      terminal portion of CFTR contains all of the structures required to build a
      regulated Cl- channel.

PMID- 7511064
TI  - [Does vascularization and the graft diameter affect the rejection reaction in
      corneal transplantation?].
AB  - The rejection (RR) is one of the most serious complications of perforating
      keratoplasty (PK). The authors evaluated in a retrospective investigation 316 PK
      made between 1986 and 1990 at the Second Ophthalmological Clinic in Prague. The
      authors investigated the number, onset, type of RR and its relation to the
      character of vascularization and size of the graft. The total number of RR was 66
      (20.9%) with a mean onset period of 6.67 months. A significantly higher incidence
      (p < 0.01) of RR was found in the group of vascularized corneas (28.0%), as
      compared with corneas without vascularization (14.71%). The difference between
      groups with a superficial and deep vascularization was not significant. The
      authors did not find a significant difference in the incidence of RR in PK with a
      7 mm diameter of the explant or smaller, as compared with explants larger than 7
      mm.

PMID- 7511063
TI  - Generalized lymphoproliferative disease in mice, caused by a point mutation in
      the Fas ligand.
AB  - Mice homozygous for lpr (lymphoproliferation) or gld (generalized
      lymphoproliferative disease) develop lymphadenopathy and suffer from autoimmune
      disease. The lpr mice have a mutation in a cell-surface protein, Fas, that
      mediates apoptosis. Fas ligand (FasL) is a tumor necrosis factor (TNF)-related
      type II membrane protein and binds to Fas. Here, mouse Fasl gene was isolated and
      localized to the gld region of mouse chromosome 1. Activated splenocytes from gld
      mice express Fasl mRNA. However, FasL in gld mice carries a point mutation in the
      C-terminal region, which is highly conserved among members of the TNF family. The
      recombinant gld FasL expressed in COS cells could not induce apoptosis in cells
      expressing Fas. These results indicate that lpr and gld are mutations in Fas and
      Fasl, respectively, and suggest important roles of the Fas system in development
      of T cells as well as cytotoxic T lymphocyte-mediated cytotoxicity.

PMID- 7511065
TI  - Variable effects of tamoxifen on human hematopoietic progenitor cell growth and
      sensitivity to doxorubicin.
AB  - To determine the influence of tamoxifen on the drug sensitivity of normal human
      hematopoietic progenitor cells, T-cell- and adherent-cell depleted human bone
      marrow mononuclear cells (T-, Ad-) were exposed in vitro to 5 microM tamoxifen
      for 24 h. The effects of tamoxifen were highly variable, as exposure to tamoxifen
      produced an increase (97% +/- 12.3%) in the growth of day-12 committed myeloid
      progenitors (CFU-GM) in only four of ten experiments utilizing bone marrow from
      different donors. When T-, Ad- myeloid progenitor cells treated with tamoxifen
      were subsequently exposed to doxorubicin, 7 of 14 experimental samples studied
      demonstrated a net increase in the number of surviving clonogenic cells as
      compared with cells exposed to doxorubicin alone. Tamoxifen also stimulated the
      growth of a more purified (CD34(+)-selected) progenitor cell population in four
      of four experiments (by 62.5% +/- 4.9%) but did not increase the survival of
      these cells upon exposure to doxorubicin; in fact, in five of ten experimental
      samples, tamoxifen enhanced cell sensitivity to doxorubicin. Taken together,
      these observations indicate that tamoxifen produces variable stimulation of
      committed myeloid progenitor cell growth in vitro. Furthermore, while under some
      circumstances, tamoxifen appears to have the capacity to enhance CFU-GM survival
      in the presence of doxorubicin, this drug combination may also result in enhanced
      toxicity to normal bone marrow progenitors.

PMID- 7511066
TI  - Lithium pharmacokinetics during cisplatin-based chemotherapy: a case report.
AB  - A 33-year-old patient, treated for several years with lithium carbonate for a
      manic depressive disorder, received four courses of combination chemotherapy
      (bleomycin, etoposide, cisplatin) after the diagnosis of disseminated testicular
      cancer. Lithium therapy was continued throughout all the courses. Serum and urine
      lithium concentrations were determined during and between all chemotherapy
      courses. During the first course a transient 64% decrease in serum lithium
      concentrations was found. This effect became less pronounced during the
      consecutive courses. The changes in serum lithium concentrations were without
      perceptible clinical significance. However, careful monitoring of serum lithium
      concentrations is mandatory in patients treated with cisplatin-based
      chemotherapy, as this is accompanied by profound disturbances of lithium
      pharmacokinetics.

PMID- 7511067
TI  - Occurrence of hepatocellular carcinoma in chronic viral hepatitis.

PMID- 7511068
TI  - Evaluation of the therapeutic effect of TAE on primary liver cancer.
AB  - The therapeutic effect of transcatheter arterial chemoembolization (TAE)
      performed on 31 patients with primary liver cancer was evaluated using the
      following procedures: (1) the alpha-fetoprotein (AFP) reduction rates and
      prognoses were analyzed according to the tumor reduction rates (TR), and (2) the
      AFP reduction rates and prognoses were also analyzed according to the tumor
      necrosis rates (TN) estimated by regarding every region with Lipiodol retention
      as being necrotic. The following results were obtained. The AFP level was 400
      ng/ml or higher in 15 patients (48%). Their AFP reduction rates were as favorably
      high as 65.4%-99.8% (mean, 88.1%), and the AFP level was normalized in 3
      patients. The cumulative survival rates after the initial treatment were
      relatively high, i.e., 78.4% in the 1st year, 58.1% in the 2nd year, and 38.7% in
      the 3rd year. These results suggested the effectiveness of the TAE treatment
      undertaken in this study. Regarding the TR, the tumor was reduced in size by 50%
      or more in only 5 patients (16%), and most patients had a TR of less than 25%. On
      the other hand, the majority, 25 patients (81%), had a TN ranging between 50% and
      less than 100%, including 7 who had a TN ranging between 50% and less than 90%
      and 18 who had a TN ranging between 90% and less than 100%. There was no
      significant correlation between the AFP reduction rate and the TN or TR.
      Regarding evaluation of the cumulative survival rates by TR and TN, the 1-year
      survival rate was lower in patients having a TR of less than 25% than in those
      having a TR of 25% or more. Patients having a TN of less than 50% showed a poor
      outcome as compared with those having a TN of 50% or more. Although the TR was
      found to be less than 50% in a majority of the patients when the therapeutic
      effect of TAE on the liver cancer was evaluated according to the TR, many of
      these patients showed a good outcome. Thus, the conventional efficacy evaluation,
      in which a tumor reduction of 50% or more is considered to be effective, should
      be reconsidered. On the other hand, the TN was found to be 50% or more in most of
      the patients, suggesting the necessity of a more detailed classification of TN.
      In relation to the survival rate, patients having a TN of less than 50% showed a
      poor outcome.

PMID- 7511069
TI  - Segmental transarterial chemoembolization with Lipiodol mixed with anticancer
      drugs for nonresectable hepatocellular carcinoma: follow-up CT and therapeutic
      results.
AB  - We developed segmental Lp-TAE, which is transcatheter hepatic sub-subsegmental,
      subsegmental, or segmental chemoembolization using Lipiodol introduced into the
      tumor-bearing hepatic sub-subsegment, subsegment, or segment as the target area.
      A total of 98 patients with nonresectable hepatocellular carcinoma (HCC)
      undergoing segmental Lp-TAE (Seg-Lp-TAE) were studied, and the relationship
      between the CT pattern observed after Seg-Lp-TAE (Seg-Lp-CT) and the therapeutic
      results obtained in those patients was evaluated. Seg-Lp-CT was classified into
      four types (type I, homogeneous; type II, defective; type III, inhomogeneous; and
      type IV, only slight accumulation, if any) according to the Lipiodol accumulation
      pattern observed after Seg-Lp-TAE. The cumulative nonrecurrence rates of type I
      were higher than those of types II-IV. The cumulative survival rates of type Ia,
      in which Lp accumulation is also seen around the main tumor, were the highest
      (93.8% at 1 year, 85.9% at 2 years, 85.9% at 3 years, and 57.3% at 4 years). The
      cumulative survival rates achieved with Seg-Lp-TAE were 89.2% at 1 year, 69.4% at
      2 years, 58.9% at 3 years, 44.0% at 4 years, and 30.2% at 5 years, which were
      higher than those achieved with conventional Lp-TAE. Seg-Lp-TAE is very useful in
      the treatment of HCC limited to one sub-subsegment, subsegment, or segment, and
      it is important to choose sub-subsegmental, subsegmental, or segmental Lp-TAE on
      the basis of the size and site of the tumor as well as the type and the number of
      feeding arteries.

PMID- 7511071
TI  - Expression and insulin-like growth factor-dependent proteolysis of insulin-like
      growth factor-binding protein-4 are regulated by cell confluence in vascular
      smooth muscle cells.
AB  - Insulin-like growth factor (IGF)-I is markedly induced after balloon injury in
      the rat aorta, where it may serve to mediate vascular repair. Because the
      bioavailability of IGF-I is modulated by IGF-binding proteins (IGFBPs), we
      examined the regulation of IGFBPs by IGFs in primary cultures of rat aortic
      smooth muscle cells (SMCs). Serum-deprived SMC-conditioned medium contains IGFBPs
      of 38 to 45 kD (only in confluent cultures), 30 kD (possibly IGFBP-2), 28 kD, and
      24 kD (IGFBP-4), the latter being the most abundant. IGF-I and IGF-II but not
      insulin evoked a marked decrease of IGFBP-4 as early as 4 hours after treatment.
      IGFBP-4 mRNA abundance, however, was entirely unaffected by IGF-I for up to 48
      hours. IGF-I analogues with high affinity for the IGF-I receptor and weak
      affinity for IGFBP paradoxically evoked a small increase in IGFBP-4, probably
      through a general increase in protein synthesis. IGF-I only minimally decreased
      IGFBP-4 content in medium of sparse cultures, whereas it completely abolished
      IGFBP-4 content in conditioned medium of superconfluent SMCs. IGF-I also evoked a
      concentration-dependent increase in the abundance of IGFBP-3 in confluent, but
      not sparse, SMCs without affecting IGFBP-3 mRNA. Addition of IGF-I to cell-free
      medium conditioned by confluent, but not by sparsely cultured, SMCs led to rapid
      degradation of IGFBP-4. Interestingly, IGFBP-4 mRNA was markedly induced in
      confluent relative to sparsely grown SMCs in an IGF-I independent fashion. Thus,
      both biosynthesis and IGF-dependent proteolysis of IGFBP-4 are increased in
      confluent SMCs. Proteolysis was maximal at 37 degrees C and was abrogated by EDTA
      and by benzamidine. Phenylmethylsulfonyl fluoride and the plasmin inhibitor
      bdellin had minor inhibitory activity, whereas aprotinin, angiotensin-converting
      enzyme inhibitors, and N-ethylmaleimide were without effect. The protease does
      not affect the structure of IGF-I as determined by reverse-phase high-performance
      liquid chromatography and size-exclusion chromatography of 125I-IGF-I incubated
      for up to 24 hours with SMC-conditioned medium containing IGFBP-4. In summary,
      SMCs elaborate a cation-dependent protease in a confluence-dependent fashion,
      which degrades bound IGFBP-4 and likely releases free structurally intact IGF-I,
      presumably to interact with the cell surface receptor and/or other IGFBPs.

PMID- 7511072
TI  - Vascular free radical release. Ex vivo and in vivo evidence for a flow-dependent
      endothelial mechanism.
AB  - Mechanisms underlying production of vascular free radicals are unclear. We
      hypothesized that changes in blood flow might serve as a physiological stimulus
      for endothelial free radical release. Intact isolated aortas from 45 rabbits were
      perfused with the spin trap alpha-phenyl-N-tert-butylnitrone (PBN, 20 mmol/L) and
      formed radical adducts detected by electron paramagnetic resonance spectroscopy
      (EPR). Sequential perfusion at 2, 7.5, and 12 mL/min changed cumulative vascular
      PBN radical adduct yields, respectively, from 3.2 +/- 0.9 to 4.1 +/- 0.7 (P <
      .05) and 7.0 +/- 1.5 (P < .005) pmol/mg with endothelium and from 3.6 +/- 1.6 to
      3.8 +/- 1.4 and 2.2 +/- 0.8 pmol/mg without endothelium (P = NS). In
      endothelialized aortas, superoxide dismutase (SOD) completely blocked flow
      induced free radical production, whereas inactivated SOD, indomethacin, and the
      nitric oxide synthetase antagonist nitro-L-arginine methyl ester (L-NAME) had no
      effect; relaxations to acetylcholine remained unchanged with higher flows. To
      assess the role of flow on in vivo radical production, femoral arterial plasma
      levels of the ascorbyl radical, a stable ascorbate oxidation product, were
      measured by direct EPR in 56 other rabbits. Ascorbyl levels were assessed at
      baseline (30.2 +/- 0.7 nmol/L) and at peak-induced iliac flow changes. Flow
      increases from 25% to 100% due to saline injections through an extracorporeal
      aortic loop induced significant dose-dependent increases in ascorbyl levels (n =
      5). In addition, after papaverine bolus injections, flow increased by 114 +/- 8%
      versus baseline, and ascorbyl levels increased by 5.4 +/- 0.7 nmol/L (n = 31, P <
      .001); similar results occurred with adenosine, isoproterenol, or hyperemia after
      30-second occlusions (P < .05, n = 4 or 5 in each group). Active SOD completely
      blocked papaverine-induced ascorbyl radical increase, despite preserved flow
      response (delta ascorbyl = 0.02 +/- 1.6 nmol/L, P = NS); inactivated SOD,
      catalase, indomethacin, and L-NAME had no effect. Blood flow decreases of 65% to
      100% due to phenylephrine or 60-second balloon occlusions were accompanied by an
      average decrease of 4.4 nmol/L (P < .05) in ascorbyl levels. No change in
      ascorbyl signal was observed when rabbit blood alone was submitted to in vitro
      flow increases through a tubing circuit. Thus, increases in blood flow trigger
      vascular free radical generation; such a response seems to involve endothelium
      derived superoxide radicals unrelated to cyclooxygenase or nitric oxide
      synthetase activities. This mechanism may contribute to explain vascular free
      radical generation in physiological or pathological circumstances.

PMID- 7511070
TI  - Prospective and randomized clinical trial for the treatment of hepatocellular
      carcinoma--a comparison between L-TAE with farmorubicin and L-TAE with
      adriamycin: preliminary results (second cooperative study). Cooperative Study
      Group for Liver Cancer Treatment of Japan.
AB  - A randomized controlled clinical trial was conducted to compare the use of
      farmorubicin (FARM) and adriamycin (ADR) in Lipiodol transcatheter arterial
      chemoembolization (L-TAE) as a treatment of hepatocellular carcinoma. In all, 192
      hospitals participated, and 415 patients were enrolled in the study during the
      period from October 1989 through December 1990, and their data were collected.
      The patients were randomly allocated to group A (FARM) or group B (ADR) by a
      central telephone registration. Several clinical characteristics were slightly
      worse in group A than in group B, but there was no statistically significant
      difference. The actual doses of FARM and ADR were 72 mg/body and 48 mg/body,
      respectively. Additional treatments, including repeated TAE or surgery, were
      given to 248 patients. The 1- and 2-year survival rates were 69% and 44% for
      group A and 74% and 57% for group B, respectively. The difference was marginally
      significant (P value in the log-rank test, 0.038). When each group of patients
      was classified into two subgroups, i.e., high-risk and low-risk categories, based
      on the severity index calculated by the Cox regression model from significant
      prognostic factors, the ADR subgroup was significantly superior to the FARM
      subgroup in the low-risk category, but there was no significant difference
      between the subgroups in the high-risk category. The change in the serum alpha
      fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the
      extent of tumor reduction did not show any significant difference between the
      groups. At the above-mentioned doses, ADR seemed to have efficacy almost the same
      as or slightly superior to that of FARM in L-TAE for the treatment of
      hepatocellular carcinoma.

PMID- 7511073
TI  - Hyperthyroidism secondary to a pituitary adenoma secreting TSH, FSH, alpha
      subunit and GH.
AB  - A 51-year-old man had been treated for hyperthyroidism with antithyroid drugs for
      8 years. He was then found to have a large pituitary adenoma with biochemical
      evidence of overproduction of TSH, FSH and alpha-subunit. Subsequent
      immunocytochemical and tissue culture studies confirmed secretion of these
      hormones. In addition, the tumour stained for GH and was capable of GH production
      in vitro. This combination of hormones produced by a pituitary adenoma has not
      been previously reported.

PMID- 7511074
TI  - Correlation of serum cytokine and acute phase reactant levels with alterations in
      weight and serum albumin in patients receiving immunotherapy with recombinant IL
      2.
AB  - Recombinant IL-2 (rIL-2) has been used alone or in combination with other
      chemotherapeutic agents to enhance host defences against cancer. Prolonged
      administration of high doses, required for clinical efficacy, may precipitate
      serious dose-limiting toxicity. rIL-2-induced 'vascular leak syndrome' leads to
      hypotension, renal insufficiency, respiratory disturbances and other organ
      dysfunctions. Serial measurements of serum cytokines and the acute phase protein
      C-reactive protein (CRP) were performed on nine patients who received high-dose
      i.v. continuous therapy with rIL-2. The influence of these immunological
      parameters upon alterations in patients' weight and serum albumin, as indicators
      of toxicity, was assessed. All patients experienced weight increases during the
      cycle (3-11% of total body weight). The serum levels of tumour necrosis factor
      (TNF-alpha) and CRP were highly predictive of alterations in patients' weight
      (both P < 0.001), while no correlation was found with IL-6 and weight change.
      Serum albumin fell linearly throughout the infusion cycle, but this showed no
      correlation with variations in serum levels of IL-6, TNF-alpha, or CRP. The
      complement components C3 and C4 were significantly reduced at the end of the
      infusion, suggesting a possible role for this cascade system in mediating these
      clinical changes. The strong association between serum TNF-alpha and weight
      change, not previously documented, further supports the hypothesis that TNF-alpha
      is a key mediator in the pathogenesis of the 'vascular leak syndrome'.

PMID- 7511075
TI  - Epitope mapping with synthetic peptides of 52-kD SSA/Ro protein reveals
      heterogeneous antibody profiles in human autoimmune sera.
AB  - The reactivity of autoantibodies present in the sera of 489 patients with
      Sjogren's syndrome (SS), systemic lupus erythematosus (SLE) and other autoimmune
      diseases was investigated by ELISA using recombinant 52-kD SSA/Ro protein (rRo52)
      and 39 overlapping synthetic peptides representing the entire sequence of Ro52.
      We report that IgG antibodies reacting with rRo52 were present in the sera of a
      large number of patients with SS (67% of patients with primary SS and 46% of
      patients with SS associated with SLE), whereas they were less frequent (10-25%)
      in SLE, rheumatoid arthritis (RA), juvenile chronic arthritis (JCA) and mixed
      connective tissue disease (MCTD), and absent in scleroderma. Among the 39
      peptides tested, five were recognized by sera from 30-65% of patients with SS,
      namely peptides representing residues 2-11, 107-122, 107-126, 277-292 and 365
      382. Patients with JCA had raised levels of IgG antibodies reacting with peptides
      2-11 and 365-382, and 51% of patients with MCTD had raised levels of IgG
      antibodies reacting with peptide 365-382. None of the five peptides was
      recognized by more than 20% of sera from patients with SLE and RA. Interestingly,
      and of importance in the field of diagnostic tests based on peptides, the
      reactivity of antibodies to the Ro52 synthetic peptides varied greatly according
      to the origin of sera. Inhibition experiments using either patients' sera or
      antibodies induced in rabbits against Ro52 peptides showed that the four domains
      2-11, 107-122, 277-292 and 365-382 are accessible on the surface of the Ro52
      protein. These regions may thus be involved in the induction of specific
      antibodies in autoimmune patients.

PMID- 7511076
TI  - Adhesion of peripheral blood lymphocytes of children with arthritis to human
      umbilical vein endothelial cells.
AB  - To determine whether adhesion of peripheral blood lymphocytes (PBL) of patients
      with juvenile rheumatoid arthritis (JRA) may be enhanced, adhesion of PBL of
      children with JRA, children with seronegative spondyloarthropathies (SSA), age
      appropriate and adult controls, to human umbilical vein endothelial cells (HUVEC)
      was assessed in vitro. B and CD4 T lymphocytes in initial, adherent, and non
      adherent cell fraction were identified by flow cytometry. B lymphocytes of all
      the younger subjects combined had a higher adherence to activated HUVEC compared
      with B lymphocytes of the adult donors. Except for greater adherence of HLA-DR+
      CD4 T cells, lymphocytes of children with JRA showed no enhanced adhesion to
      either unactivated or activated HUVEC. The percentage of B cells adherent to
      activated HUVEC in each of the subject groups was 1.5-3.6-fold higher than
      adherent CD4 T lymphocytes. Surface analyses indicated higher percentages of
      CD49d (alpha 4)+ and CD29 (beta 1)+ CD4 T lymphocytes in adherent cells, but less
      of a differential in CD49 (alpha 4)+ and no difference in CD29 (beta 1)+ B
      lymphocytes. There were fewer Leu-8 (L-selectin)+ B and Leu-8+ CD4 T cells among
      adherent cells. The data suggest a greater adhesive capacity of B lymphocytes
      compared with CD4 T lymphocytes which is unrelated to disease, and the
      possibility that B lymphocytes may utilize adhesion molecules distinct from those
      of CD4 T lymphocytes. Only a small subset of T cells of patients with JRA may
      have an enhanced capacity for adhesion to endothelium.

PMID- 7511078
TI  - Recombinant gp120 induces IL-10 in resting peripheral blood mononuclear cells;
      correlation with the induction of other cytokines.
AB  - Immunological abnormalities present in HIV-1-infected individuals often reflect
      an imbalance of cytokine production. The HIV-1 gp120 has the ability to induce a
      number of cytokines, and to enhance immunoglobulin release by normal peripheral
      blood mononuclear cells (PBMC) in vitro, in the absence of IL-2 production and of
      lymphoproliferation. This study provides evidence that gp120 is a potent IL-10
      inducer in normal PBMC cultures. The pattern of other cytokines induced by gp120
      includes interferon-alpha (IFN-alpha) and IFN-gamma, tumour necrosis factor-alpha
      (TNF-alpha), IL-6, IL-1 alpha and -beta, and not IL-2 and IL-4. These findings
      further define the pattern of cytokine release induced by gp120 on human resting
      PBMC. Furthermore, the present findings roughly parallel those observed both in
      the sera of patients and in the mononuclear cells from HIV+ individuals early
      after infection, suggesting that gp120 could be a good candidate as one of the
      agents responsible for cytokine dysregulation observed in HIV-1-infected
      individuals.

PMID- 7511077
TI  - HIV-1 induces tumour necrosis factor and IL-1 gene expression in primary human
      macrophages independent of productive infection.
AB  - Cytokines such as tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta may play
      a role in immunopathogenesis of AIDS. We studied early effects (0.5-48 h) of
      monocytotropic (ADA) or lymphotropic (IIIB) strains of HIV-1 on TNF-alpha and IL
      1 beta mRNA expression in primary human macrophages by a semi-quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Three-day-old
      monocyte-derived macrophages were exposed either to tissue culture supernatants
      containing virus (at multiplicity of infection (m.o.i.) of 0.05) or to control
      supernatants free of virions and gp120. ADA strain, but not IIIB, replicated in
      primary tissue culture-differentiated macrophages (TCDM). Soluble CD4 (sCD4) was
      used to inhibit binding of both strains to macrophages. We found that TNF-alpha
      and IL-1 beta gene expression was induced by both strains 0.5-3 h after addition
      of virus, and that enhanced expression of both cytokines was inhibited by sCD4.
      We conclude that CD4-dependent binding to the cell surface is sufficient to
      enhance TNF-alpha and IL-1 beta mRNA, whereas productive viral replication in
      primary human macrophages is not required. Therefore, similar pathways regulate
      gene expression of TNF-alpha and IL-1 beta by macrophages during initial
      infection by HIV-1 in vitro.

PMID- 7511079
TI  - CD8 lymphocytosis in primary cytomegalovirus (CMV) infection of allograft
      recipients: expansion of an uncommon CD8+ CD57- subset and its progressive
      replacement by CD8+ CD57+ T cells.
AB  - Allograft recipients undergoing cytomegalovirus infection present increased
      proportions of circulating CD8+ lymphocytes. A longitudinal study of 11 kidney
      and five liver allograft recipients with primary CMV infection but no other
      etiological factor of graft dysfunction revealed selective imbalances of
      peripheral blood CD8+ T cell subsets. Initially, CMV viraemia is associated with
      elevated CD8+bright T cell numbers and T cell activation. Activation markers fall
      to normal when viral cultures become negative (before the end of the first
      month). During the second to sixth month, most (12/16) patients keep up high CD8+
      T cell counts (1050-2900 CD8+ cells/mm3), comprising an uncommon CD8+ T cell
      subset, as 45-73% of CD8+bright lymphocytes were CD3+ and TCR alpha beta+, but
      were not stained by anti-CD28, CD11b, CD16, CD56, and CD57 antibody.
      Unexpectedly, CD8+CD57+ T cells, a hallmark of CMV infection, do not appear until
      the second to sixth month of primary CMV infection, and their numbers increase
      progressively thereafter. They become the predominant CD8+ T cell subset after 6
      months of infection and their persistence for several (up to 4) years is strongly
      correlated (r = 0.87) with expansion of CD8+ cells. By analysis with MoAbs, there
      was no bias towards the use of particular TCR-V beta gene families at any time of
      primary CMV infection. Persistence of CD8 lymphocytosis is thus directly related
      to the rate of expansion of an uncommon CD8+CD57- subset and its progressive
      replacement by CD8+CD57+ T cells that are chronically elicited by CMV.

PMID- 7511080
TI  - Natural autoantibodies, IgG antibodies to tetanus toxoid and CD5+ B cells in
      patients with Mediterranean visceral leishmaniasis. The Leishmania Study Group.
AB  - Natural autoantibodies (NaAb) and IgG antibodies to tetanus toxoid (TT) were
      analysed in the sera of 38 children with active visceral leishmaniasis (VL)
      previously vaccinated with TT and in 30 healthy controls matched for sex and age.
      Patients exhibited high levels of NaAb to a panel of self antigens (tubulin,
      myosin, myoglobin, actin) contrasting to a low level of IgG to TT. Analysis of
      the circulating B cells in 26 untreated patients showed a low percentage of CD5+
      per total B cells (3-66%, mean 36.6%) compared with 14 normal controls (17.8
      66.6%, mean 52.7%) (P < 0.001). Evaluation of these parameters after antimonial
      therapy showed a significant decrease of the level of the NaAb (P < 0.0005), and
      a spontaneous increase of the level of the IgG to TT without any vaccine boosting
      (P < 0.01). In contrast, there was a significant increase in CD5+ B cells (P <
      0.0005). This result suggests that CD5+ B cells may be sequestrated in
      parasitized lymphoid organs and may be released after remission. These findings
      show that the polyclonal B cell activation that occurs during active VL involves
      mainly B cells bearing NaAb and are in favour of a functional dichotomy of B
      cells.

PMID- 7511082
TI  - Subpopulations of T and B cells in perinatally HIV-infected and noninfected age
      matched children compared with those in adults.
AB  - Peripheral blood mononuclear cells were quantified for the subsets of CD4, CD8,
      and CD19 lymphocytes by using CD45RA (2H4), CD29(4B4), CD57, CD5, CD10, Leu8, HLA
      DR, and TCR gamma delta-1 monoclonal antibodies and dual color
      immunofluorescence. A comparative analysis of lymphocyte subpopulations was made
      among 52 HIV-infected and 50 age-matched control children and 30 HIV-seropositive
      and 27 negative control adults. A significant decrease in the CD4+CD45RA+ "naive"
      cells was much more marked in HIV-infected children than in HIV-infected adults.
      A significant percentage increase in the CD4+CD29+ "memory" cells was observed in
      HIV-infected children but not in infected adults; however, the absolute numbers
      were usually decreased in all age groups. The mean percentage and absolute
      numbers of CD4+CD7+ and CD4+Leu8+ cells were decreased in HIV-infected children,
      although usually not significantly. The CD3+TCR gamma delta-1+ did not show any
      change in the infected children tested. The mean percentage and absolute number
      of the CD8+HLA-DR+ cells increased significantly in HIV-infected persons of all
      ages. The CD8+CD57+ cells were increased in percentage and absolute number in HIV
      infected children ages 1-4 and 4-8 years. In the adults, no change was noted in
      either the percentage or absolute number of CD19+CD5+ B cells, a finding similar
      to that noted in HIV-infected children above 1 year of age. Although adults
      showed a significant decrease in both percentage and numbers of CD5- B cells, an
      increase was noted in the 7- to 12-month-old HIV-infected children. The
      CD19+CD10+ cells showed a slight but significant decrease in the youngest age
      group and a significant increase in the older age groups of HIV-infected
      children. These findings indicate that several lymphocyte subpopulations are
      altered differentially during HIV infection in children of varying ages and in
      adults.

PMID- 7511081
TI  - T cell activation in pediatric AIDS pathogenesis: three-color immunophenotyping.
AB  - Immune activation is an important component of HIV disease in adults that may
      reflect a protective host response and/or be a component of immunopathogenesis.
      The goals of this study were to gain understanding of T cell activation in
      pediatric HIV disease, to assess the usefulness of T cell activation markers as
      surrogates for disease progression and/or early identification of infection in
      infants at risk, and to determine any advantages of three- compared to two-color
      flow cytometric immunophenotyping for the above assessments. We examined the
      expression of cell-surface activation antigens on the CD4 and CD8 T cells of 26
      HIV-infected and 40 HIV-seronegative age-matched control children. Compared with
      controls, HIV-infected children showed a slight but not significant decrease in
      the proportion of CD4 cells that coexpressed CD45RA and L-selectin (mean of 83 vs
      75% for < 2 years of age, 76 vs 62% for 2-3 years, 64 vs 56% for > or = 4 years).
      CD4 cells coexpressing CD38 and HLA-DR were significantly increased in HIV+
      children (mean of 2 vs 6% for < 2 years of age, 3 vs 11% for 2-3 years, 2 vs 8%
      for > or = 4 years). There was a striking and significant increase in the
      proportion of CD8 cells coexpressing CD38 and HLA-DR (mean of 5 vs. 25% for < 2
      years, 10 vs 41% for 2-3 years, 6 vs 31% for > or = 4 years); this double
      positive population of CD8 cells included cells that were approximately 1 log
      brighter for the expression of CD38 than for that of CD38 single-positive cells.
      There was a significant reduction in CD45RA+ CD8 cells (means of 92 vs 71% for <
      2 years of age, 88 vs 50% for 2-3 years, 80 vs 57% for > or = 4 years) and an
      increase in CD57+ CD8 cells (mean of 4 vs 8% for < 2 years of age, 8 vs 22% for 2
      3 years, 19 vs 31% for > or = 4 years) in HIV+ children. The inclusion of CD3 as
      an anchor marker for CD8 cell subsets to limit the analysis to CD3+ CD8 cells did
      not substantially alter the data nor enhance the differences between infected and
      control children compared with the analysis of all CD8 cells.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7511083
TI  - Identification of myelin basic proteins in circulating immune complexes
      associated with lepromatous leprosy.
AB  - Circulating immune complexes (CIC) were first measured in lepromatous patients
      (LL) by the 125I-C1q binding assay and the polyethylene glycol (PEG)
      precipitation test. High levels were found by both methods (95 and 90% of
      positives, respectively). LL-CIC were investigated for the presence of neural
      antigens. CIC were precipitated in 3.5% PEG, filtered through protein A-Sepharose
      affinity chromatography, eluted with glycine-HCl, pH 2.8, and washed with PBS;
      fractions after CIC dissociation were studied by SDS-PAGE and Western blotting.
      The LL-CIC PEG precipitates and the glycine-HCl eluates were positive in 76 and
      71% respectively against anti-myelin basic proteins (MBP) monoclonal antibody,
      showing a single band at 15-25 kDa similar to the one obtained incubating MBP
      with anti-MBP. No reaction was detected with CIC-PBS fractions; strips were
      incubated with other anti-neural antibodies such as anti-glial fibrillary acidic
      proteins, anti-S-100, and anti-neurofilaments, without any reactivity. Our
      results demonstrate that LL-CIC contain MBP as an antigen; its significance could
      be related to the pathogenesis of leprosy since the liberation of MBP after
      Mycobacterium leprae nerve damage may elicit anti-MBP autoantibodies to myelin
      breakdown, which reacts with peripheral nerve MBP inducing CIC formation. This
      mechanism may be important in demyelination and destruction of nerve in leprosy.

PMID- 7511084
TI  - Autoantigenic properties of native and denatured glutamic acid decarboxylase:
      evidence for a conformational epitope.
AB  - The frequency of antibodies to GAD (anti-GAD) in insulin-dependent diabetes
      mellitus (IDDM) varies greatly according to the type of assay employed. We
      therefore examined the immunoassay characteristics of diabetic sera using GAD
      purified from porcine brain and shown to contain both isoforms. Sera from 38
      patients with IDDM, including 1 patient with both stiff-man syndrome (SMS) and
      IDDM, were studied for anti-GAD by radioimmunoprecipitation (RIP), Western
      blotting, and dot-blotting. The sera were selected according to reactivity in the
      RIP assay. There was a good correlation between potency of the RIP reaction at
      the screening dilution of 1:2 and the endpoint dilution in the assay which ranged
      from 1:2 to 1:30,000 for IDDM sera, and 1:300,000 for the SMS serum. Of the 38
      sera positive for anti-GAD by RIP, only 6 had antibodies detectable by Western
      blotting, and all gave an RIP titer of at least 1:250. The low frequency of
      antibodies by Western blotting was explicable by denaturation of the antigen.
      Thus, using a dot-blotting assay in which reactivity to untreated "native" GAD
      was compared with reactivity to GAD after denaturation by reduction with 2
      mercaptoethanol and boiling, 20 of the 38 IDDM sera reacted unequivocally with
      the native GAD compared with only 2 that reacted with denatured GAD after
      reduction and boiling. The sera were tested for their capacity to inhibit the
      catalytic activity of GAD, but only the high-titer serum from the patient with
      SMS did so. Our study further validates the RIP assay for anti-GAD and
      establishes that anti-GAD exists in IDDM over a wide range of titers that
      correlate with other assay characteristics, and also indicates that the
      conformational autoantibody epitope on GAD is susceptible to alteration under
      denaturing conditions.

PMID- 7511087
TI  - Hydroxyapatite orbital implants. Scanning with technetium-99m MDP.
AB  - Porous hydroxyapatite spheres are an ideal prosthetic device for orbital
      implantation because they are incorporated into soft tissues. Once vascularized,
      an eye prosthesis can be coupled to the sphere by a peg placed within a central
      motility hole. This hole should not be drilled while the sphere is avascular
      because of the risk of infection. Radionuclide scanning with Tc-99m methylene
      diphosphonate has been used to assess implant vascular ingrowth because
      radiophosphonate deposition within the sphere parallels vascularization. Using
      this technique, the authors examined the hydroxyapatite implants of 15 patients 6
      months following insertion. Results showed that complete vascularization is best
      defined by planar imaging rather than SPECT. While the relative intensity of
      implant activity may be an important feature, uniformity of activity is probably
      more significant.

PMID- 7511086
TI  - A role for histones and ubiquitin in lupus nephritis?
AB  - Glomerulonephritis frequently develops in Systemic lupus erythematosus (SLE) but
      the pathogenesis is still poorly understood. Experimental evidence now suggests
      that histones can participate in immune complex formation in lupus nephritis. In
      a retrospective study, using samples from Northern and Southern Europe, Japan and
      South America, we searched for glomerular deposits of histones, both in native
      and ubiquitinated forms, in renal biopsy specimens from 48 patients with SLE and
      70 cases of glomerulonephritis from patients without SLE. Positive glomerular
      immunofluorescent staining was revealed with rabbit antibodies to synthetic
      peptide 1-21 of histone H3, 22-45 of ubiquitin and to the branched region of
      ubiquitinated histone H2A (U-H2A) in 65% (31/48), 29% (14/48) and 54% (26/48) of
      the cases of SLE respectively. In total positive staining with at least one of
      the antibodies was seen in 36/48 (75%) cases. The staining was granular in nature
      and was present in capillary and mesangial areas. Only 3% (2/70) of non-SLE renal
      biopsies revealed positive staining with the above antibodies. None of the biopsy
      specimens from SLE patients were positive for ss- or ds-DNA, when tested with
      intercalating dyes. Serum samples were available from 15/48 SLE cases and were
      analysed with peptides and parent proteins by ELISA; epitopes in the N-terminal
      regions of core histones and in the C-terminus of histone H1 were often
      recognised by IgG antibodies in SLE sera, as was ubiquitin and the branched
      octapeptide of U-H2A. These results support the notion that the nuclear
      autoantigens histone and ubiquitin may be involved in the induction of
      glomerulonephritis in human SLE.

PMID- 7511085
TI  - Peripheral T cell response to A-gliadin in celiac disease: differential
      processing and presentation capacities of Epstein-Barr-transformed B cells and
      fibroblasts.
AB  - Celiac disease (CD) is a small intestinal disorder characterized by the
      malabsorption of most nutrients. Disease pathogenesis appears to be associated
      with immune-mediated pathology. Susceptibility is associated with genes coding
      for DQw2 class II molecules. In the present report we investigated T cell
      responses to A-gliadin (AGL), a major alpha-gliadin component known to activate
      disease. Gliadin-specific lines were generated from a CD patient and a normal
      donor. Three major points were revealed by the analysis of these T cells: (1) On
      the basis of mapping experiments using Epstein-Barr virus (EBV) lines and DR
      transfected fibroblasts and DR-, DP-, and DQ-specific monoclonal antibodies
      (mAb), all responses appeared to be DR-restricted. Thus, in contrast to the
      strong association of disease susceptibility with DQ molecules, no DQ-restricted,
      gliadin-specific response was detectable. (2) Fine specificity analysis, using a
      panel of synthetic peptides spanning the entire alpha-gliadin component molecule,
      revealed that the clones derived from the normal donor were DR53-restricted and
      AGL 21-40-specific, while clones derived from the CD patient were DR7-restricted
      and peptide 1-20-specific. (3) Both whole AGL and AGL 1-20 were presented to the
      patient-derived clones with much higher efficiency by DDR-transfected fibroblasts
      than by EBV lines. These data suggested that fibroblasts processed this
      determinant efficiently, while EBV lines were unable to do so. Indeed, analysis
      of a panel of truncated AGL 1-20 analogs revealed that peptide AGL 1-8, which
      contained the minimal T cell epitope, was presented with equal efficiency by
      fixed or irradiated EBV and irradiated DR7-transfected fibroblasts.

PMID- 7511089
TI  - Placing blood on the target: a challenge for visually impaired persons.
AB  - An individualized, blood glucose self-monitoring procedure for those who are
      visually impaired must be developed, taught, practiced, observed, and reviewed.
      Effective teaching requires understanding functional vision loss, observing
      safety precautions, organizing the work area, obtaining an adequate blood sample,
      ensuring accurate placement of blood on the strip, and cleaning up. Thoroughness
      and repetition enable the visually impaired person to perform the procedure
      safely and confidently.

PMID- 7511088
TI  - Active chloride transport in the pigmented rabbit conjunctiva.
AB  - The present study demonstrates, for the first time, that the excised pigmented
      rabbit conjunctiva is a tight barrier capable of active Cl- transport. The
      transepithelial potential difference was 17.7 +/- 0.8 mV (tear-side negative),
      the short-circuit current was 14.5 +/- 0.7 microA/cm2, and the transconjunctival
      resistance was 1.3 +/- 0.1 k omega.cm2 for n = 45 tissues. Various inhibitors
      including ouabain (a Na+/K(+)-ATPase inhibitor), amiloride (a Na+ transport
      blocker), N-phenylanthranilic acid (a chloride transport inhibitor), bumetanide
      (an inhibitor of Na(+)-(K+)-Cl- cotransport process), and BaCl2 (a K+ channel
      blocker) were used on the mucosal and serosal sides of the tissue mounted in
      Ussing chambers to determine the involvement of the respective ion transport
      processes in the observed short-circuit current across the conjunctiva. The
      results suggest that a Cl- conductive pathway is present on the mucosal side of
      the conjunctiva, whereas Na+/K(+)-ATPase, Na(+)-(K+)-Cl- cotransport process, and
      K+ conductive pathways are present on its serosal side. Amiloride-sensitive Na(+)
      conductive pathways do not appear to be present on either side of the pigmented
      rabbit conjunctiva.

PMID- 7511090
TI  - Understanding young children's health beliefs and diabetes regimen adherence.
AB  - Previous studies of chronic illness management in children have focused mainly on
      parents' health beliefs. However, children's health beliefs also can be an
      important factor in predicting adherence. Indeed, children 6 to 10 years old
      spend most waking hours away from home, are under less parental supervision, and
      are becoming more responsible for their own care. The purpose of this study was
      to develop a pictorial, multi-item instrument to measure dimensions of the Health
      Belief Model (HBM) and self-efficacy (SE), designed specifically for children
      with diabetes, thus making it possible to examine both the parent's and child's
      health beliefs; to explore the relationship between their beliefs; and to examine
      the extent to which these beliefs are predictors of adherence and metabolic
      control.

PMID- 7511092
TI  - A region in the human glycoprotein hormone alpha-subunit important in holoprotein
      formation and receptor binding.
AB  - Using site-directed mutagenesis of the human glycoprotein hormone alpha-subunit,
      we have shown that single replacements of Ala36 and Pro38 with Glu and Asp,
      respectively, result in mutant subunits that do not bind significantly to hCG
      beta. In contrast, the replacement of Lys44 with Ala did not interfere with hCG
      beta binding, but the resulting holoprotein failed to exhibit high affinity
      binding to the LH/CG receptor. These results in conjunction with other data
      suggest that the region of human alpha between positions 33-45 contains several
      amino acid residues that participate in subunit binding and others that function
      in receptor binding.

PMID- 7511091
TI  - Differential tissue regulation of insulin-like growth factor-I content and
      binding proteins after endotoxin.
AB  - The purpose of the present study was to investigate the regulation of plasma and
      tissue levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-1, 
      2, and -3 (IGFBP-1, -2, and -3) in rats injected with Escherichia coli
      lipopolysaccharide (LPS), a component of the outer cell wall of gram-negative
      bacteria. When injected iv into conscious overnight fasted rats, plasma IGF-I
      levels were initially decreased within 1 h, maximally depressed at 4 h, and still
      only 35-45% of control values at 24 h. GH levels were reduced as early as 30 min
      after LPS, averaged 80-90% of control values between 1-4 h, but had returned to
      basal levels by 24 h. The magnitude and duration of these changes were similar
      regardless of whether 100 or 10 micrograms/100 g BW (LD20 and LD0, respectively)
      LPS were injected. Plasma levels of IGFBP-1 and a 28K mol wt BP (BP-28K) were
      elevated 2- to 3-fold 4 h after LPS treatment, whereas IGFBP-3 and -2 levels were
      unchanged. The elevation in plasma IGFBP-1 and IGFBP-28K was observed as early as
      1 h and was sustained for up to 24 h after LPS treatment. IGF-I levels were
      decreased 30-50% in liver, pituitary, and skeletal muscle, unchanged in brain,
      and elevated 5-fold in kidney in response to LPS. Of the tissues sampled, IGFBP-3
      and -2 were selectively elevated in liver after LPS treatment. IGFBP-1 was
      increased in liver, muscle, and kidney in response to LPS. The level of the
      28,000 mol wt BP was increased in liver (83%) and not changed in muscle or brain.
      These data indicate that LPS produces both rapid and sustained alterations in
      circulating levels of GH, IGF-I, and IGFBPs. Furthermore, there were marked
      tissue-specific changes in levels of IGF-I and IGFBPs. LPS-induced changes in
      plasma and tissue IGFBP-3 were not regulated by changes in GH, and changes in
      insulin could not explain the alterations in IGFBP-1 and -2. These results
      suggest that after the injection of LPS, changes in IGF-I and IGFBP levels are
      regulated by a mechanism(s) different from those previously described.

PMID- 7511093
TI  - Involvement of nitric oxide in the regulation of gonadotropin-releasing hormone
      release from the GT1-1 neuronal cell line.
AB  - A role for nitric oxide (NO) in the regulation of hypothalamic neurohormone
      secretion has been suggested. The aim of the present study was to establish a
      direct involvement of this novel intracellular regulatory molecule in the control
      of GnRH release. For this purpose, the GT1-1 GnRH-secreting continuous cell line
      was treated with various agents that can modify the endogenous NO synthase
      activity or, alternatively, with substances that can liberate NO, mimicking an
      increased concentration of this molecule in the cell. Treatment of GT1-1 cells
      with increasing concentrations of L-arginine, the direct precursor of NO,
      produced a marked reduction of norepinephrine-stimulated GnRH release despite a
      lack of effect on basal secretion. Similarly, the NO donors SIN-1 and acidified
      NaNO2 potently reduced basal as well as KCl-stimulated GnRH secretion.
      Conversely, sodium nitroprusside caused a significant inhibition of KCl
      stimulated, but not basal, GnRH secretion. Addition of these agents to GT1-1
      cells resulted in a marked increase in intracellular cGMP accumulation. Addition
      of the NO synthase inhibitors N-nitro-L-arginine and N-nitro-L-arginine methyl
      ester stimulated basal GnRH secretion without modifying norepinephrine- or KCl
      stimulated release. In addition, treatment of GT1-1 cells with both L-arginine
      analogs produced a significant inhibition of the basal cGMP concentration.
      Together, these data suggest an inhibitory role for NO in the control of GnRH
      secretion from GT1-1 cells.

PMID- 7511094
TI  - Insulin receptor substrate-1 (IRS-1) expression in rat brain.
AB  - IRS-1 is phosphorylated on tyrosine residues after insulin stimulation and
      participates in the early events of signal transduction in peripheral insulin
      sensitive tissues. This study determined whether neuronal populations in the rat
      olfactory bulb and hippocampus (brain regions which have very high concentrations
      of insulin receptors) also express IRS-1 and contain phosphotyrosine, using in
      situ hybridization, receptor binding, and immunocytochemistry. IRS-1 mRNA was
      colocalized with insulin receptor mRNA in neuron cell bodies of hippocampus and
      olfactory bulb. Similarly, IRS-1 immunoreactivity in hippocampus and olfactory
      bulb was concentrated in layers that contain synapses of these neurons and have
      both high insulin binding and phosphotyrosine levels. Thus, IRS-1 and insulin
      receptors are coexpressed in discrete populations of neurons, suggesting a signal
      transduction mechanism by which insulin may influence metabolism and gene
      expression in the brain.

PMID- 7511095
TI  - Insulin-like growth factor binding proteins are transcribed by preimplantation
      mouse embryos.
AB  - Preimplantation embryos have been reported to synthesize insulin-like growth
      factors (IGF) and their receptors, and reproductive tract fluid has been found to
      contain insulin and IGF I. In this communication, we report that all stages of
      preimplantation mouse embryos transcribe IGF binding proteins (IGF-BP) 2, 3 and
      4, and that blastocysts also transcribe IGF-BP6. IGF-BP5 was not detected at any
      preimplantation stage. Reproductive tract cells in proximity to preimplantation
      mouse embryos transcribe all of IGF-BP2 through 6. Thus studies of the mechanisms
      of IGF action on preimplantation mouse development must consider the IGF-BP.

PMID- 7511096
TI  - Direct detection of insulin-like growth factor II (IGF-II) by chemiluminescence
      without interference by IGF binding proteins.
AB  - A dot blot method for the detection of picogram quantities of human and rat
      insulin-like growth factor II (IGF-II) in serum-free conditioned media is
      described. The crossreactivity of human recombinant IGF-I in the assay was < 10%.
      None of the IGF binding proteins (IGFBP 1-6) diminished the IGF-II signal. In
      contrast, significant interference by the IGFBPs was observed when the same
      concentrations of IGFBPs and 125I-IGF-II were used in a radioimmunoassay which
      utilized the same antibody. Why IGF-II is detected in the dot blot assay without
      IGFBP interference is not understood. We speculate that the conformation of the
      IGF-II/binding protein complex may be altered by binding to the nitrocellulose,
      exposing the IGF-II epitope that is recognized by the antibody. IGF-II was
      detected in 1 microliter of serum-free conditioned media from BRL 3A cells (which
      secrete IGF-II) while no signal was generated by 50 microliters of BRL 3A2
      conditioned media (which do not secrete IGF-II). In summary, this method is ideal
      for screening cells in serum free-culture for production of IGF-II without the
      need for separation of IGF-II from cell derived IGFBPs.

PMID- 7511097
TI  - Proteolysis of insulin-like growth factor binding protein-5 by pregnancy serum
      and amniotic fluid.
AB  - Incubation of iodinated recombinant human insulin-like growth factor binding
      protein (rhIGFBP)-5 with pregnancy serum or amniotic fluid resulted in the
      formation of 22- and 15 kDa fragments. Non-pregnancy serum did not contain IGFBP
      5 proteolytic activity. Size fractionation revealed the proteolytic activity both
      in serum and amniotic fluid in a > 100 kDa fraction which co-eluted in gel
      filtration with proteins of approx. 200 kDa. The IGFBP-5 protease activity was
      inhibited by EDTA, phenanthroline and PMSF. The formation of proteolytic
      fragments was also observed using 125I labeled rhIGFBP-3 and -4 but not with
      rhIGFBP-1 or -6 as substrate. The data demonstrate that pregnancy serum and
      amniotic fluid contain a very similar cation-dependent serine protease which
      degrades IGFBP-3, -4 and -5.

PMID- 7511098
TI  - Precise quantitation of chloramphenicol acetyl transferase reporter mRNA by
      competitive polymerase chain reaction.
AB  - A strategy, based on competitive polymerase chain reaction (PCR) after reverse
      transcription, was developed to quantitate mRNA of the E. coli chloramphenicol
      acetyl transferase (CAT) gene. Precise quantitation of this rare mRNA is achieved
      by co-amplification of a constant amount of the complementary DNA (cDNA) with
      successive dilutions of a competitive DNA template of known concentration and
      with the use of the same primers. The unique EcoRI site located in the CAT coding
      sequence has been abolished in the competitive DNA. The two oligonucleotide
      primers used are both located in the CAT coding sequence at equal distance from
      the EcoRI site. After amplification, the PCR products from the cDNA to be
      quantified and from the competitor DNA are discriminated by EcoRI digestion,
      followed by separation of the resulting fragments by agarose gel electrophoresis.
      DNA amplified from the target cDNA is the only DNA digested by EcoRI into two
      fragments of identical size co-migrating in an agarose gel. After ethidium
      bromide staining, comparison of the intensity of fluorescence of the resulting
      bands in a competition series permits us to estimate precisely the amount of CAT
      cDNA and therefore of the mRNA to be quantified.

PMID- 7511099
TI  - Characterization of E-PHA-reactive alpha-fetoprotein isoforms by two-dimensional
      lectin affinity electrophoresis.
AB  - Erythroagglutinating phytohemagglutinin (E-PHA)-dependent isoforms of human alpha
      fetoprotein (AFP) from cord blood were analyzed for their carbohydrate structures
      by two-dimensional electrophoresis with E-PHA combined with extended agarose gel
      electrophoresis or with affinity electrophoresis with concanavalin A or
      Allomyrina dichtoma lectin. By means of neuraminidase and/or beta-galactosidase
      treatment, AFP-P2 was identified as alpha 2-->6 disialo-AFP, AFP-P3 as having
      biantennary structures with alpha 2-->6 monosialylated galactose of the Mannose
      (Man) alpha 1-->6 arm, AFP-P4 as having alpha 2-->6 monosialylated galactose of
      the Man alpha 1-->3 arm, and AFP-P5 as disialo-AFP with alpha 2-->3 sialylated
      galactose of the Man alpha 1-->6 antenna with the alpha 2-->6 sialylated
      galactose of the other antenna. Desialylated AFP with the terminal galactose of
      the Man alpha 1-->6 antenna with or without the galactose of the other arm also
      had a migration of AFP-P4, and other hydrolytic intermediates without the
      terminal galactose of the Man alpha 1-->6 arm with and without the galactose of
      the other antenna had mobilities of AFP-P3s and AFP-P3, respectively. Thus, the
      present system of two-dimensional lectin affinity electrophoreses would provide a
      model for the determination of the sugar chain structure of glycoproteins.

PMID- 7511101
TI  - Distinct functions of capsid protein in assembly and movement of tobacco etch
      potyvirus in plants.
AB  - Tobacco etch potyvirus engineered to express the reporter protein beta
      glucuronidase (TEV-GUS) was used for direct observation and quantitation of virus
      translocation in plants. Four TEV-GUS mutants were generated containing capsid
      proteins (CPs) with single amino acid substitutions (R154D and D198R), a double
      substitution (DR), or a deletion of part of the N-terminal domain (delta N). Each
      modified virus replicated as well as the parental virus in protoplasts, but was
      defective in cell-to-cell movement through inoculated leaves. The R154D, D198R
      and DR mutants were restricted essentially to single, initially infected cells.
      The delta N variant exhibited slow cell-to-cell movement in inoculated leaves,
      but was unable to move systemically due to a lack of entry into or replication in
      vascular-associated cells. Both cell-to-cell and systemic movement defects of
      each mutant were rescued in transgenic plants expressing wild-type TEV CP. Cell
      to-cell movement, but not systemic movement, of the DR mutant was rescued
      partially in transgenic plants expressing TEV CP lacking the C-terminal domain,
      and in plants expressing CP from the heterologous potyvirus, potato virus Y.
      Despite comparable levels of accumulation of parental virus and each mutant in
      symptomatic tissue of TEV CP-expressing transgenic plants, virions were detected
      only in parental virus- and delta N mutant-infected plants, as revealed using
      three independent assays. These data suggest that the potyvirus CP possesses
      distinct, separable activities required for virion assembly, cell-to-cell
      movement and long-distance transport.

PMID- 7511100
TI  - Generation of interleukin-6 receptor antagonists by molecular-modeling guided
      mutagenesis of residues important for gp130 activation.
AB  - Interleukin-6 (IL-6) drives the sequential assembly of a receptor complex formed
      by the IL-6 receptor (IL-6R alpha) and the signal transducing subunit, gp130. A
      model of human IL-6 (hIL-6) was constructed by homology using the structure of
      bovine granulocyte colony stimulating factor. The modeled cytokine was predicted
      to interact sequentially with the cytokine binding domains of IL-6R alpha and
      gp130 bridging them in a way similar to that of the interaction between growth
      hormone and its homodimeric receptor. Several residues on helices A and C which
      were predicted as contact points between IL-6 and gp130 and therefore essential
      for IL-6 signal transduction, were subjected to site-directed mutagenesis
      individually or in combined form. Interestingly, while single amino acid changes
      never produced major alterations in IL-6 bioactivity, a subset of double mutants
      of Y31 and G35 showed a considerable reduction of biological activity and were
      selectively impaired from associating with gp130 in binding assays in vitro,
      while they maintained wild-type affinity towards hIL-6-R alpha. More importantly,
      we demonstrated the antagonistic effect of mutant Y31D/G35F versus wild-type IL
      6.

PMID- 7511102
TI  - The effect of inosiplex in subacute sclerosing panencephalitis: a clinical and
      laboratory study.
AB  - The immunomodulatory action of inosiplex, a drug frequently used in subacute
      sclerosing panencephalitis (SSPE), varies according to its dose and the subjects'
      immune status. In order to assess its effect in children and adolescents with
      SSPE, inosiplex (25-50 mg/kg/day) was given to 9 patients aged 7-17 years. Their
      clinical and immunologic status was evaluated before and after 2 months'
      treatment. Lymphocyte mitogenic response decreased in 6 cases. These patients
      were clinically stable or improving during this period. Changes in cytotoxicity
      (increased in 5/6 patients) and suppressor cell function (increased in 4/8 and
      decreased in 4/8) were not significant nor associated with any particular
      clinical course. Our results suggest that inosiplex at this dose is more likely
      to suppress lymphocyte proliferation in SSPE and this is not due to advancing
      disease. Longer follow-up of clinical and laboratory findings seems to be
      indicated in therapeutic trials in SSPE.

PMID- 7511103
TI  - Is endotoxin-induced hypotension related to nitric oxide formation?
AB  - Nitric oxide (NO), an endothelium-derived relaxing factor (EDRF), is released by
      different types of cells under the influence of endotoxin and various cytokines:
      a causative role of endothelium-derived NO in the endotoxin-induced hypotension
      has thus been suggested. To test the hypothesis that NO may be involved in the
      acute hypotension following endotoxin challenge, we administered a competitive
      inhibitor of NO synthase, L-N-monomethylarginine (L-NMMA) to anesthetized dogs in
      the presence and absence of endotoxin. Dogs were randomly allocated to three
      groups. Group 1 (n = 3) was given Escherichia coli endotoxin (3 mg/kg, i.v.),
      group 2 (n = 3) was given L-NMMA (5 mg/kg, i.v. bolus) 15 min after endotoxin and
      group 3 (n = 3) was given L-NMMA only. One additional dog was given L-arginine
      (100 mg/kg, i.v. bolus) after L-NMMA and endotoxin to reverse the inhibition of
      NO synthase. In each animal, saline was infused intravenously throughout the
      experiment to restore and maintain pulmonary artery occluded pressure at baseline
      level. After L-NMMA, the increases in mean arterial pressure were similar in
      group 2 (from 55 +/- 18 to 75 +/- 15 mm Hg, p < 0.01) and in group 3 (from 107 +/
      27 to 128 +/- 24 mm Hg, p < 0.01). Systemic vascular resistance increased from
      2,994 +/- 72 to 3,658 +/- 673 dyn.s.cm-5 (p < 0.01) in group 3. Group 1 had lower
      plasma lactate levels than group 2 (3.5 +/- 2.3 +/- vs. 2.0 +/- 1.6 mEq/l, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511104
TI  - Stage A1 prostate cancer: follow-up with digital rectal exploration, prostate
      markers, fine-needle aspiration, ultrasonographically guided needle biopsy and
      biopsies of the residual prostate with resectoscope.
AB  - From January 1985 to December 1990, we performed 921 TURP and 23 retropubic
      adenomectomies. In 70 patients (7.4%) histological examination revealed an
      incidental carcinoma of the prostate (stage A), 51 of which (72.8%) were A1 and
      19 (27.2%) stage A2. In our classification A1 covers cases with < 3 G1 focal
      lesions [Boxer, 1977]. Thirteen of the A2 cases underwent radical prostatectomy:
      1 pT1G1-2, 9 pT2G1-2, 3 pT3G2 (TNM 1978); the remaining 6 were given palliative
      treatment. The 51 stage A1 patients were recalled for follow-up evaluation, only
      20 came for checking. They were reassessed by means of DRE, markers, prostate
      cytologic aspiration, echo-guided transperineal needle biopsy and resection of
      the prostatic cavity. Our experience seems to suggest that, if we define A1 as <
      3 G1 chips or less, this stage is to be considered an incidental illness that
      seems not to require further treatment, but only a policy of surveillance with
      yearly markers, DRE and echo-guided needle biopsy.

PMID- 7511105
TI  - Intraurethral catheter in high-risk patients with urinary retention: 3 years of
      experience.
AB  - A new intraurethral catheter (IUC) developed by Nissenkorn has been inserted in
      43 patients in the last 3 years. We reserved this device for very selected
      patients in urinary retention due to prostatic obstruction with operative
      contraindications or limited life expectancy. The device is simple, very easy to
      insert under direct cystoscopic control. Thirty-six patients (84%) were able to
      void without incontinence or significant post-voiding residual. We noticed 4
      early and 5 late migrations of the prosthesis into the bladder. Symptomatic
      urinary infection occurred in 5 patients and bacteriuria occurred in 6 patients.
      The IUC remained in place up to 9 months without encrustations. It is well
      tolerated, easy to insert and remove and inexpensive. We believe that this IUC is
      a valid alternative to a long-term indwelling catheter for patients in poor
      general conditions unfit for surgery.

PMID- 7511106
TI  - Limitation of shock-wave-induced renal tubular dysfunction by nifedipine.
AB  - In a prospective randomized study, the effects of the calcium entry blocker
      nifedipine on shock-wave-induced tubular impairment were studied. 24 patients
      with renal pelvic or calyceal stones undergoing anesthesia-free extra-corporeal
      shock wave lithotripsy (ESWL) without ancillary measures were randomly assigned
      to the nifedipine group (n = 12) or the control group (n = 12). Four doses of
      nifedipine (10 mg t.i.d.) were given orally, starting the night before ESWL.
      Controls received no medication. To assess renal tubular function, the urinary
      excretion of alpha 1-microglobulin (A1M), N-acetyl-beta-glucosaminidase (NAG) and
      Tamm-Horsfall protein (THP) were measured before, immediately, 12 and 24 h after
      ESWL. After lithotripsy, there was a rise in urinary A1M and NAG which was
      significantly higher in the control than in the nifedipine group. THP, a
      glycoprotein synthesized by distal tubular cells, fell significantly less in the
      nifedipine group compared to the controls. Our results indicate that nifedipine
      exhibits a protective effect on shock-wave-induced tubular damage similar to
      verapamil. The underlying mechanisms are not clarified yet, direct actions on
      tubular cells and interference with renal hemodynamics have to be discussed.

PMID- 7511108
TI  - Antagonism of substance P and related peptides by RP 67580 and CP-96,345, at
      tachykinin NK1 receptor sites, in the rat urinary bladder.
AB  - Tonic contraction of rat urinary bladder was elicited in vitro and in vivo by
      substance P, two selective NK1 receptor agonists, septide ([pGlu6,Pro9]substance
      P-(6-11)) and [Sar9,Met(O2)11]substance P, and an NK2 agonist,
      [Lys5,MeLeu9,Nle10]neurokinin A-(4-10), but not by senktide
      (succinyl[Asp6,MePhe8]substance P-(6-11)), an NK3 agonist. Substance P only
      stimulated the NK1 receptors of smooth muscle. The non-peptide selective NK1
      receptor antagonists, RP 67580 and CP-96,345, both inhibited substance P-induced
      contraction (pKB values 6.7 and 5.7; ED50 = 1.4 and 5.0 mg/kg i.v., respectively)
      and septide-induced contraction (pKB values 7.5 and 6.5; ED50 = 0.076 and 0.250
      mg/kg i.v., respectively). Both antagonists, at lower doses, also inhibited
      substance P- and septide-induced plasma extravasation. That both antagonists
      blocked the effects of septide much more than the effects of substance P suggests
      the existence of an NK1 receptor subtype or isoform. Selective NK1 receptor
      antagonists, by blocking both spasm and plasma extravasation in the urinary
      bladder, would be useful for treating substance P-related motor disorders and
      cystitis.

PMID- 7511107
TI  - Inhibitory effect of norathyriol, a xanthone from Tripterospermum lanceolatum, on
      cutaneous plasma extravasation.
AB  - Norathyriol, a xanthone aglycon isolated from Tripterospermum lanceolatum, was
      demonstrated to reduce the plasma leakage elicited by the passive cutaneous
      anaphylactic reaction in normal as well as in adrenalectomized mice. Capsaicin
      pretreatment greatly suppressed the local edema caused by antidromic stimulation
      of the saphenous nerve. The plasma exudation of neurogenic inflammation was also
      reduced in mice treated with norathyriol, diphenhydramine and methysergide, but
      not with indomethacin. Norathyriol, cyproheptadine and diphenhydramine combined
      with methysergide suppressed the ear edema caused by injection of compound 48/80,
      bradykinin and substance P into the ear. However, indomethacin did not affect
      this phlogist-induced edema response. Histamine- and serotonin-induced plasma
      exudation in ear edema was also reduced by norathyriol. In isolated rat
      peritoneal mast cell preparations, norathyriol produced a dose-dependent
      inhibition of histamine and beta-glucuronidase release from mast cells challenged
      by compound 48/80, bradykinin and substance P. In compound 48/80-pretreated mice,
      norathyriol at higher concentrations suppressed the bradykinin- and substance P
      induced ear edema to a significantly greater extent than diphenhydramine combined
      with methysergide did. These data indicate that the inhibitory effect of
      norathyriol on local edema is not due to the release of steroid hormones from the
      adrenal gland, but is probably partly due to suppression of mast cell
      degranulation and hence reduce the release of chemical mediators which increase
      vascular permeability, and partly, at least in higher doses, due to protection of
      the vasculature from challenge by various mediators.

PMID- 7511109
TI  - Cyclothiazide potentiates agonist responses at human AMPA/kainate receptors
      expressed in oocytes.
AB  - Cloned human AMPA/kainate subunits were functionally expressed in Xenopus
      oocytes. Cyclothiazide potentiated kainate-evoked currents by 682 +/- 122% (mean
      +/- S.E.M., n = 5), 1396 +/- 55% (n = 4), and 690 +/- 40% (n = 14) in oocytes
      expressing GluR1, GluR2, and GluR1 + GluR2 receptors, respectively. AMPA (alpha
      amino-3-hydroxy-5-methyl-4-isoxazole proprionate)-induced currents were also
      potentiated by cyclothiazide. GYKI 52466 (1-(4-amino-phenyl)-4-methyl-7,8
      methylendioxyl-5H-2,3-benzod++ + iazepine hydrochloride) attenuated cyclothiazide
      potentiation in all cases. Thus, modulatory sites for cyclothiazide and GYKI
      52466 exist on individual human AMPA/kainate receptor subunits. Additionally,
      kainate appears to act as a desensitizing partial agonist at human GluR1 and
      GluR2 receptor subunits.

PMID- 7511110
TI  - Physiological oxygen tension is relevant to MHC-1 expression, spontaneous
      transformation, and interferon response of in vitro aging murine fibroblasts.
AB  - Working from the hypothesis that modest deviations from physiological oxygen
      tension will influence cell characteristics important for infections/immunity and
      tumor development, cells were studied at three oxygen tensions during in vitro
      aging. Primary mouse embryo fibroblasts were established and subsequently
      passaged at 3, 6, and 18 kPa oxygen tension (6 representing normal tissue tension
      and 18 being the conventionally tension at in vitro cultures). The growth rate
      was slightly higher at 6 than 3 and 18 kPa. All cultures eventually stopped
      growing and subsequently transformed to nonmalignant cells with unlimited growth
      capacity. Cells kept at 3 kPa reached the highest number of cell doublings before
      crisis. Stimulation with PolyI:C resulted in detectable interferon response only
      at the high oxygen tension, and after transformation none of the cultures
      responded with interferon production. Expression of the major histocompatibility
      complex H-2K was elevated above and below physiological oxygen tension,
      indicating regulatory processes optimizing MHC expression at about physiological
      oxygen tension.

PMID- 7511111
TI  - Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase.
AB  - Recently, we reported that curcumin (diferuloylmethane) inhibits the growth of
      several different kinds of tumor cells. In order to investigate the mechanism of
      this inhibition, we examined the effects of curcumin on different protein
      kinases: highly purified protein kinase A (PkA), protein kinase C (PkC),
      protamine kinase (cPK), phosphorylase kinase (PhK), autophosphorylation-activated
      protein kinase (AK) and pp60c-src tyrosine kinase. While all kinases tested were
      inhibited by curcumin, only PhK was completely inhibited at relatively lower
      concentrations. At around 0.1 mM curcumin, PhK, pp60c-src, PkC, PkA, AK, and cPK
      were inhibited by 98%, 40%, 15%, 10%, 1%, and 0.5%, respectively. Lineweaver-Burk
      plot analysis indicated that curcumin is a non-competitive inhibitor of PhK with
      a Ki of 0.075 mM. Overall, our results indicate that curcumin is a potent and
      selective inhibitor of phosphorylase kinase, a key regulatory enzyme involved in
      the metabolism of glycogen. This has important implications for the anti
      proliferative effects of curcumin.

PMID- 7511112
TI  - Human immunodeficiency virus uses tRNA(Lys,3) as primer for reverse transcription
      in HeLa-CD4+ cells.
AB  - Significant amounts of different tRNA molecules are present in retroviral
      particles, but one specific tRNA species functions as primer in reverse
      transcription. It is generally believed that the HIV-1 virus uses the tRNA(Lys,3)
      molecule as primer. This is based on sequence complementarity between the 3' end
      of tRNA(Lys,3) and the primer-binding site (PBS) on HIV-1 genomic RNA. Recent
      biochemical analyses indicated that tRNA(LYs,3) is indeed incorporated into viral
      particles. Interestingly, tRNA(Lys,3) could not be detected in virions produced
      by HeLa-CD4+ cells [(1992) Biochem. Biophys. Res. Commun. 185, 1105-1115]. In
      order to test whether alternative tRNA molecules can function as primer in HIV
      replication, we performed a series of experiments based on the observation that
      tRNA primer sequences are inherited by the viral progeny. We cultured HIV-1 for
      prolonged periods of time in HeLa-CD4+ cells, but did not detect sequence changes
      in the PBS region. Furthermore, we found PBS-mutants to be replication
      incompetent, again suggesting that HIV-1 solely uses tRNA(Lys,3) as primer. Most
      importantly, we obtained revertants of one such PBS-mutant, which had restored a
      wild-type PBS sequence. This tRNA(Lys,3)-mediated repair demonstrates a general
      requirement for this primer in HIV-1 reverse transcription.

PMID- 7511113
TI  - The crystal structure of human CskSH3: structural diversity near the RT-Src and n
      Src loop.
AB  - SH3 domains are modules occurring in diverse proteins, ranging from cytoskeletal
      proteins to signaling proteins, such as tyrosine kinases. The crystal structure
      of the SH3 domain of Csk (c-Src specific tyrosine kinase) has been refined at a
      resolution of 2.5 A, with an R-factor of 22.4%. The structure is very similar to
      the FynSH3 crystal structure. When comparing CskSH3 and FynSH3 it is seen that
      the structural and charge differences of the RT-Src loop and the n-Src loop, near
      the conserved Trp47, correlate with different binding properties of these SH3
      domains. The structure comparison suggests that those glycines and acid residues
      which are very well conserved in the SH3 sequences are important for the
      stability of the SH3 fold.

PMID- 7511114
TI  - Exogenous NG-hydroxyl-L-arginine causes nitrite production in vascular smooth
      muscle cells in the absence of nitric oxide synthase activity.
AB  - Nitric oxide (NO) production from exogenous NG-hydroxy-L-arginine (OH-L-Arg) was
      investigated in rat aortic smooth muscle cells in culture by measuring nitrite
      accumulation in the culture medium. As well, the interaction between OH-L-Arg and
      L-arginine uptake via the y+ cationic amino acid transporter was studied. In
      cells without NO-synthase activity, OH-L-Arg (1-1000 microM) induced a dose
      dependent nitrite production with a half-maximal effective concentration (EC50)
      of 18.0 +/- 1.5 microM (n = 4-7). This nitrite accumulation was not inhibited by
      the NO-synthase inhibitor NG-nitro-L-arginine methyl ester, L-NAME (300 microM).
      In contrast, it was abolished by miconazole (100 microM), an inhibitor of
      cytochrome P450. Incubation of vascular smooth muscle cells with LPS (10
      micrograms/ml) induced an L-NAME inhibited nitrite accumulation, but did not
      enhance the OH-L-Arg induced nitrite production. OH-L-Arg and other cationic
      amino acids, L-lysine and L-ornithine, competitively inhibited [3H]-L-arginine
      uptake in rat aortic smooth muscle cells, with inhibition constants of 195 +/- 23
      microM (n = 12), 260 +/- 40 microM (n = 5) and 330 +/- 10 microM (n = 5),
      respectively. These results show that OH-L-Arg is recognized by the cationic L
      amino acid carrier present in vascular smooth muscle cells can be oxidized to NO
      and nitrite in these cells in the absence of NO-synthase, probably by cytochrome
      P450 or by a reaction involving a cytochrome P450 by-product.

PMID- 7511115
TI  - A simple method for demonstration of eosinophils in frozen sections.
AB  - Tissue eosinophils can be easily and specifically demonstrated in frozen sections
      after substrateless incubation with 3,3'-diaminobenzidine (DAB) at neutral pH.
      Under such conditions, other cells possessing endogenous peroxidatic activity
      (neutrophils, macrophages) do not stain, whereas staining of mitochondria-rich
      cells due to cytochrome oxidase activity can be avoided by a short prefixation of
      sections in glutaraldehyde-containing fixatives. The method can be useful in
      cases when a rapid screening of tissue eosinophils is required.

PMID- 7511116
TI  - Effect of lindane on phosphatidylinositol synthesis by cerebral cortex after
      acute and subchronic treatment.
AB  - 1. The incorporation of myo-[2-3H]inositol into phosphatidylinositols was
      unmodified in brain cortex miniprisms from convulsant rats. 2. However, the
      incorporation had increased by 300-400% in non convulsant rats which had received
      the same amount of lindane at a lower concentration. 3. This result suggests that
      phosphatidylinositols are implicated in the convulsion syndrome. 4. Experiments
      with lindane added in vitro were performed with both subchronically lindane
      intoxicated and untreated rats. 5. The results show an interesting lack of
      parallelism. 6. This might indicate the development of some resistance to the
      effects of lindane, possibly as the result of complex compensatory changes in
      inositol lipid biosynthesis.

PMID- 7511117
TI  - Purification and some properties of apurinic/apyrimidinic DNA endonucleases in
      rat liver.
AB  - 1. Three kinds of apurinic/apyrimidinic (AP) DNA endonucleases, APcI, APcII,
      APcIII were purified from rat liver chromatin. 2. Molecular weights of APcI,
      APcII and APcIII were 30,000, 42,000 and 13,000 Da, which have isoelectric points
      of 7.2, 6.3 and 6.2, respectively. 3. Mg2+ was essential for the activities of
      these 3 enzymes, and sulfhydryl compounds (beta-mercaptoethanol) had a
      stimulatory effect on the enzyme activities while N-ethylmaleimide and HgCl2
      inhibited the enzyme activity. 4. Km values of APcI, APcII and APcIII for AP site
      of DNA were 0.53, 0.27 and 0.36 microM, respectively, and AMP was the most potent
      inhibitor to these three enzymes among nucleotides tested.

PMID- 7511118
TI  - RNA synthesis in isolated mitochondria from brain cortex, cerebellum and stem:
      evidence of different transcriptional rates.
AB  - 1. A system for studying RNA synthesis in isolated sheep brain mitochondria was
      set up to investigate the transcriptional activity of different brain regions
      (cortex, cerebellum and brain stem). In this system, mitochondrial DNA is
      transcribed and RNA processed in a way that faithfully reproduces the in vivo
      process. 2. The comparison of the electrophoretic patterns of the mitochondrial
      DNA transcription products showed that although they were qualitatively similar,
      there were large differences in the rate of mitochondrial DNA transcription of
      the three regions studied, cerebellum and brain stem showing transcriptional
      rates which were 34 and 18% respectively of that of cerebral cortex.

PMID- 7511119
TI  - The isolation and partial characterization of alpha 2-macroglobulin from the
      serum of the ostrich (Struthio camelus.
AB  - 1. alpha 2-Macroglobulin (alpha 2M) activity is present in the serum of the
      ostrich, Struthio camelus. The chromogenic synthetic peptide substrates BAPNA and
      ATNA were hydrolysed by trypsin and chymotrypsin, respectively, in the presence
      of ostrich serum and the alpha 2 M in ostrich serum protected trypsin from being
      inhibited by soybean trypsin inhibitor. Ostrich alpha 2M proved to be a potent
      inhibitor of bovine pancreatic trypsin and chymotrypsin. 2. alpha 2M was purified
      to apparent homogeneity by PEG precipitation, DEAE-Toyopearl 650M, Bio-Gel A-5m
      and Zn(2+)-affinity chromatography. 3. Ostrich alpha 2M migrated as a single band
      (M(r) 779,000 during non-denaturing gradient gel electrophoresis and showed
      increased mobility after reaction with trypsin. Denaturation dissociated ostrich
      alpha 2M into half-molecules. Denaturation with reduction further dissociated the
      protein into quarter-subunits. 4. Isoelectric focusing revealed a pI of 5.3. 5.
      The amino acid composition of ostrich alpha 2M is typical of an alpha 2M,
      comparing favourably with those of other animal species. The carbohydrate
      composition of the purified protein, in percentage dry weight of the molecule,
      was galactose: mannose (1:1), 4.55; N-acetylglucosamine 2.35; N-acetylneuraminic
      acid, 0.58; and fucose, 0.77. 6. alpha 2M was assessed immunologically by
      Ouchterlony double-diffusion and Western blot analysis with polyvalent antisera
      directed against ostrich alpha 2M. 7. Ostrich alpha 2M seems to show many
      physical, chemical and kinetic properties similar to those of other known alpha
      2M(s), but is expected to differ from other alpha Ms when considering the primary
      structure of the bait region, the area differing among alpha Ms from different
      species and determining its specificity.

PMID- 7511121
TI  - Hypomelanosis of Ito (incontinentia pigmenti achromians).

PMID- 7511120
TI  - The septum pellucidum and spatial ability of children with optic nerve
      hypoplasia.
AB  - Animal studies suggest that spatial skills are dependent on an intact septum
      pellucidum. This theory was tested by comparing patients who were visually
      impaired due to bilateral optic nerve hypoplasia: 13 with a septum pellucidum
      were compared with six children without a septum pellucidum. There was no
      difference in spatial ability. The finding of an absent septum pellucidum may
      only indicate the timing of a congenital brain insult, and it cannot be used to
      predict specific clinical, neuroendocrinological, cognitive or spatial
      abnormalities.

PMID- 7511122
TI  - Structure of the O9 antigen from Burkholderia (Pseudomonas) cepacia.
AB  - The O9 antigen of Burkholderia (Pseudomonas) cepacia has the following
      disaccharide repeating-unit: -->4)-alpha-D-Glcp-(1-->3)-alpha-L-Rhap-(1--> The
      same unit is present in the O antigens of Serratia marcescens strain S1254 and
      serogroup O4 (predominantly acetylated at O-2 of rhamnose in the latter case).

PMID- 7511124
TI  - Vitamin E deficiency impairs the modifications of mitochondrial membrane
      potential and mass in rat splenocytes stimulated to proliferate.
AB  - This study was designed to evaluate the time-dependent changes of mitochondrial
      membrane potential and mass during Con-A-induced proliferation of splenic
      lymphocytes from rat fed a normal or a vitamin E deficient diet. Rhodamine 123
      and Nonyl Acridine Orange were used as specific probes to monitor the membrane
      potential and mass of mitochondria, respectively, by means of flow cytometry. The
      results demonstrate that the increase of Rh-123 and NAO uptake observed in cells
      from normally fed rats was prevented by vitamin E deficiency, at any time
      considered. After 72 h from Con A stimulation, 62% of cells from controls, as
      against 16% of cells from vitamin E deficient rats, showed hyperpolarized
      mitochondria. At the same time, in this last group, 60% of cells had depolarized
      organelles. The same pattern was observed considering the changes of
      mitochondrial mass, measured using NAO as a probe. These data support that
      mitogenic stimulation induced an increase of the respiratory activity of
      mitochondria with subsequent production of superoxide radicals. This resulted in
      depolarization and loss of mass of the organelles if the intracellular level of
      vitamin E is not adequate.

PMID- 7511123
TI  - Insertional mutation on mouse chromosome 18 with vestibular and craniofacial
      abnormalities.
AB  - A dominant mutation was generated in transgenic mice as a consequence of
      insertional mutation. Heterozygous mice from transgenic line 9257 (Tg9257) are
      hyperactive with bidirectional circling behavior and have a distinctive facial
      appearance due to hypoplasia of the nasal bone. Morphological analysis of the
      inner ear revealed asymmetric abnormalities of the horizontal canal and
      flattening or invagination of the crista ampullaris, which can account for the
      circling behavior. The sensory epithelium appeared to be normal. The transgene
      insertion site was localized by in situ hybridization to the B1 band of mouse
      chromosome 18. Genetic mapping in an interspecific backcross demonstrated the
      gene order centromere--Tg9257--8.8 +/- 3.4--Grl-1, Egr-1, Fgf-1, Apc--14.7 +/-
      4.3--Pdgfr. The phenotype and the mapping data suggest that the transgene may be
      inserted at the Twirler locus. Homozygosity for the transgene results in prenatal
      lethality, but compound heterozygotes carrying the Tw allele and the transgene
      are viable. The function of the closely linked ataxia locus is not disrupted by
      the transgene insertion. This insertional mutant will provide molecular access to
      genes located in the Twirler region of mouse chromosome 18.

PMID- 7511125
TI  - [Clozapine-induced agranulocytosis].

PMID- 7511127
TI  - Role of Na,K-ATPase in regulating acidification of early rat liver endocytic
      vesicles.
AB  - Endocytic vesicles are acidified by an electrogenic proton pump and a parallel
      chloride conductance; however, acidification might be decreased if electrogenic
      transporters, such as Na,K-ATPase, that increase vesicle interior-positive
      membrane potential were also present. We examined this issue in early rat liver
      endosomes using ion substitution and inhibitors to alter Na,K-ATPase activity.
      These early endosomes, labeled for 2 min with the fluorescent fluid-phase marker
      fluorescein isothiocyanate-dextran, consistently acidified faster than endosomes
      similarly labeled for a 10-min period. In chloride-free media initial rates of
      acidification of early endosomes were faster in K+ media than in Na+ medium,
      although addition of K+ to Na+ or Na+ to K+ media to allow Na,K-ATPase to
      function did not decrease the rate of acidification. In chloride-containing
      media, rates were the same regardless of cation composition. The Na,K-ATPase
      inhibitor vanadate was prepared from orthovanadate by several methods, all of
      which inhibited liver ATPase activity. Two hundred mumol/L vanadate, prepared Cl(
      )-free, tended to decrease rates of acidification in all media tested and these
      effects achieved statistical significance in Cl(-)-free media containing 150
      mmol/L K+ or mixtures of Na+ and K+ and in 145 mmol/L KCl/5 mmol/L NaCl medium.
      Vanadate stocks pH-adjusted with hydrogen chloride increased rates of
      acidification in sodium gluconate buffers, probably as a result of the effects of
      the included Cl-. Five mmol/L ouabain (loaded into vesicles by endocytosis) and
      the membrane-permeable analog strophanthidin (2 mmol/L) both markedly inhibited
      endosome acidification, regardless of buffer ion composition. Collectively, these
      results suggest that Na,K-ATPase does not regulate acidification of rat liver
      early endocytic vesicles, that vanadate may modestly inhibit endosome
      acidification and that ouabain at high concentrations may inhibit acidification
      from the vesicle interior face.

PMID- 7511126
TI  - Hair analysis by infrared microscopy for drugs of abuse.
AB  - Hair analysis overcomes many of the drug testing problems associated with
      urinalysis. However, hair analysis has its own unique problem in that passive
      contamination of the exterior surface of the hair can taint the analysis with
      false positive. Infrared microscopy can examine the interior of the hair and
      differentiate passive contamination from drugs absorbed into the hair from
      ingestion. By microtoming the hair either cross-sectionally or laterally,
      infrared spectra can be obtained of the cortex and medulla of a single hair with
      a nominal spatial resolution of 10 microns. Three dimensional infrared imaging is
      possible with Fourier transform infrared (FT-IR) microscopy and yields a plot
      that can be understood by the layman.

PMID- 7511128
TI  - Risk of hepatitis C virus infection in hemodialysis patients.

PMID- 7511129
TI  - Characterization and enrichment of fetal rat hepatoblasts by immunoadsorption
      ("panning") and fluorescence-activated cell sorting.
AB  - We developed methods for enriching fetal hepatoblasts by combining panning and
      multiparametric fluorescence-activated cell sorting. In unpurified, dissociated
      fetal liver cell suspensions of embryonic age day 15, 3.2% +/- 1.3% and 2.5% +/-
      0.7% cells expressed albumin and alpha-fetoprotein, respectively. The remainder
      exhibited a hemopoietic, endothelial or stromal cell phenotype. Cells were panned
      first with an antibody to red blood cells to remove erythroid cells and then with
      monoclonal antibodies OX-43/OX-44 to remove hemopoietic and endothelial cells.
      This procedure eliminated 84% of fetal hepatic cells, with enrichment of the
      remainder for albumin or alpha-fetoprotein expression (up to sixfold increase).
      Flow cytometric analysis of unlabeled cells revealed two populations, which
      differed in granularity and autofluorescence. After panning, fluorescence
      activated cell sorting for agranular cells yielded OX-43/44-positive cells that
      were essentially all hemopoietic precursor cells or OX-43/44-negative cells that
      were mostly hemopoietic precursor cells, along with 3.0% +/- 0.7% alpha
      fetoprotein-positive cells. In contrast, sorting for granular, OX-43/44-negative
      cells enriched for predominantly alpha-fetoprotein-positive, parenchymal
      precursor cells (75.1% +/- 4.7%). Multiparametric flow cytometric analysis of the
      expression of an oval cell antigen, OC.3, which is a bile duct and putative liver
      stem cell marker, showed that most OC.3-positive cells coexpressed OX-43/OX-44
      and morphologically were hemopoietic precursor cells. However, approximately 30%
      of the OX-43/44-negative, granular cells expressed OC.3. Although the
      physiological significance of OC.3-positive hepatoblasts remains to be
      determined, the ability to isolate distinct liver cell populations by means of
      fluorescence-activated cell sorting should facilitate further studies.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7511130
TI  - Plasmin and thrombin inhibitors in essentially untreated patients with coronary
      artery spasm.
AB  - We examined activities or levels of plasmin and thrombin inhibitors in
      essentially untreated patients with angiographically documented coronary artery
      spasm. The patients received the ergonovine malate provocation test and were
      classified into two groups: (a) those with significant coronary artery spasm that
      produced reduction of the internal luminal diameter of 50% or greater with chest
      pain and change of electrocardiography (n = 18), and (b) those without coronary
      artery spasm (n = 17). There was no significant differences in alpha 1
      antitrypsin and alpha 2-macroglobulin levels, and C1-inactivator activity between
      the control and patients with coronary artery spasm. On the other hand, the lower
      antithrombin III and alpha 2-plasmin inhibitor activities were noted in patients
      with coronary artery spasm than the control. Thrombin/antithrombin III complex
      and alpha 2-plasmin inhibitor/plasmin complex levels were significantly higher in
      coronary artery spasm patients. These results suggest that the coagulation and
      fibrinolytic systems may maintain their equilibrium in untreated patients with
      coronary artery spasm.

PMID- 7511131
TI  - Efficient Fmoc/solid-phase peptide synthesis of O-phosphotyrosyl-containing
      peptides and their use as phosphatase substrates.
AB  - A general synthetic method for the efficient preparation of Tyr(P)-containing
      peptides is described by the use of Fmoc-Tyr(PO3tBu2)-OH in Fmoc/solid-phase
      synthesis followed by simultaneous cleavage of the peptide from the resin and
      peptide deprotection by acidolytic treatment. The applicability of this approach
      is demonstrated by the synthesis of H-Ser-Ser-Ser-Tyr(P)-Tyr(P)-OH.TFA and the
      synthesis of the phosphorylated forms of the two physiological peptides,
      angiotensin II and neurotensin 8-13. In addition, the three phosphorylated
      peptides were used as substrates in the study of the local specificity
      determinants of T-cell protein tyrosine phosphatase. In a competition assay using
      32P-radiolabeled [Tyr(P)]4-angiotensin II, both unlabeled synthetic [Tyr(P)]4
      angiotensin II and Ser-Ser-Ser-Tyr(P)-Tyr(P) reduced the release of 32P and
      indicated that they efficiently competed as substrates for the phosphatase.
      Conversely, [Tyr(P)]4-neurotensin 8-13 was ineffective as a competitive substrate
      and indicated that this particular Tyr(P)-containing peptide sequence was not
      recognized by the enzyme. The marked difference in the recognition of Asp-Arg-Val
      Tyr(P)-Ile-His-Pro-Phe and Arg-Arg-Pro-Tyr(P)-Ile-Leu is consistent with the
      presence of an acidic residue in the -3 position relative to the Tyr(P) residue.

PMID- 7511132
TI  - Calcium channel modulators modify K opioid-induced inhibition of C-fiber-evoked
      spinal reflexes in rat.
AB  - The role of L-type Ca2+ channels on the kappa opioid-induced depression of spinal
      afferent transmission was assessed in spinalized rats, through recording of the C
      fiber-evoked spinal flexor reflex. Six successive i.t. doses of the K agonist U
      50,488H produced a dose-dependent decrease of the C-reflex duration (ID50: 25.7
      nmol), the log dose-response relationship being shifted to left by pretreatment
      with 5 mg/kg i.v. of the calcium channel blocker verapamil, or to right by
      pretreatment with .25 mg/kg i.v. of the calcium channel agonist Bay K8644.
      Verapamil and Bay K8644, administered i.v. after U-50,488H i.t., respectively
      potentiated or antagonized the depressor effect of the K ligand on the reflex.
      The results point to a role for Ca2+ availability as a factor involved in
      depression of afferent nociceptive transmission by K opioids at the spinal cord.

PMID- 7511135
TI  - Biased representation of immunoglobulin heavy chain variable region subgroups in
      chronic lymphocytic leukemia.
AB  - The distribution of three immunoglobulin heavy chain variable region gene
      subgroups (VH1, 3 and 5) was investigated, using the polymerase chain reaction
      technique, in 53 patients with chronic lymphocytic leukemia. Thirty-seven
      patients displayed rearrangements of one of the above three gene segments. Over
      representation of the VH5 subgroup was observed relative to its small size.

PMID- 7511133
TI  - Inoculation of BCL1 lymphoma cells into CSJL/J F1 mice inhibits acute
      experimental autoimmune encephalomyelitis.
AB  - T cell vaccination, which protects rodents against experimental autoimmune
      encephalomyelitis (EAE), has been shown to induce anti-idiotypic response in the
      T cell compartment. CD5 B cells (B1 cells) are the main source of natural
      autoantibodies, and are often characterized by high idiotypic connectivity. In
      this study we examined the possibility that idiotypic connectivity in the B cell
      compartment may also play a role in the regulation of EAE. We inoculated CSJLF1
      mice (H-2d,s) with a CD5 B cell line, the BCL1 lymphoma cells (H-2d), and
      subsequently induced EAE. The injection of as few as 1,000 BCL1 lymphoma cells
      significantly blocked the development of EAE. Injection of CD5-negative myeloma
      cells (SP2) had no effect on the pathogenesis of the disease. Unlike control
      animals, lymphocytes from BCL1 lymphoma-injected mice significantly proliferate
      in response to interleukin-5, a growth factor to CD5 B cells. The proliferative
      response of lymphocytes from BCL1 inoculated mice to mitogenic stimulation was
      rather unchanged, indicating that no general immunosuppression has been induced
      by inoculating BCLJ lymphoma. These experiments suggest that CD5 B cells may be
      involved in the regulation of EAE.

PMID- 7511136
TI  - Platinum drug delivery and radiation for locally advanced prostate cancer.
AB  - Combined therapies of cisplatin and radiation have resulted in clinical reports
      of apparent efficacious control of locoregional cancer and enhanced survival.
      Mechanisms of interaction between platinum and radiation that may explain these
      clinical observations all have in common the prediction that higher
      concentrations of platinum in all tumor cells close in time to irradiation should
      lead to greater potentiation of radiation-induced killing of those cells.
      Cisplatin is thus viewed as providing some radiation-equivalent, or a radiation
      dose-effect factor, for sterilization of tumors. One disease site that has not
      been well investigated for response to cisplatin plus radiation therapy, but that
      could benefit from it, is locally advanced prostate cancer. A body of literature
      now supports the view that local control of stage C (T3, N0, M0) prostate cancer
      is correlated with disease-free survival. This correlation makes prostate cancer
      a candidate for potentially achieving improved cure rates following local tumor
      sterilization by combining cisplatin with radiation therapy. The need and
      approaches to optimize delivery of cisplatin within tumor tissue is explored.
      Increasing cisplatin concentration to all the cells of a tumor, i.e.,
      homogeneously delivering systemic high-dose cisplatin, should benefit the
      efficacious response otherwise expected for cisplatin combined with radiation.
      Strategies to increase the homogeneity of cisplatin delivery to a tumor are
      considered to be those that increase perfusion to that tumor. Vasoactive agents
      used in anticancer protocols are especially considered for their potential value
      in serving to increase tumor perfusion. These protocol-inclusive agents include
      certain cytokines and L-arginine antagonists, and should be better managed and
      accepted in practice compared to other vasoactive agents that need to be
      developed as specific additives to protocol designs.

PMID- 7511134
TI  - Overnight secretion pattern of growth hormone, sex hormone binding globulin,
      insulin-like growth factor-1 and its binding protein in obese and non-obese women
      with polycystic ovarian disease.
AB  - The pathophysiological mechanism underlying polycystic ovarian disease (PCOD) is
      different in obese and lean women. In obese patients the basic disorder is
      insulin resistance and hyperinsulinemia. In non-obese women the dominant
      derangement is a relative excess of luteinizing hormone (LH) and growth hormone
      (GH) production. The levels of GH, LH, sex hormone binding globulin (SHBG) and
      insulin-like growth factor binding protein-1 (IGFBP-1) were significantly lower
      and insulin levels considerably higher in obese PCOD women as compared to their
      non-obese counterparts. There was, however, no difference in the mean IGF-1
      levels found in these two groups. The present study was designed to investigate
      whether, in addition to the mean levels, the overnight pattern of GH, IGF-1,
      IGFBP-1 and SHBG differed in obese women with polycystic ovaries as compared to
      that observed in the non-obese PCOD patients. Eight women with PCOD diagnosed by
      clinical, sonographic and hormonal means were studied. Four had basal body mass
      index exceeding 27. Blood samples were collected every 20 min over a period of 8
      h, starting at 23:00 h. Twenty-four samples were collected from each patient and
      examined in one batch for GH, IGF-1, IGFBP-1, SHBG and insulin. The secretion
      patterns of the above substances during the late night (23:00-03:00 h) and early
      morning (03:00-07:00 h) hours were examined and compared in obese and non-obese
      PCOD women. Neither GH nor IGF-1 showed a distinct overnight secretion pattern.
      The overnight secretion patterns of IGFBP-1 and SHBG were similar in obese and
      non-obese women--the former showing a constant rising during the night and the
      latter exhibiting a converse trend. The integrated insulin levels were much
      higher during the late night as compared to early morning hours in all patients.
      It is proposed that the specific secretion pattern of IGFBP-1 is not directly
      dependent on body fat mass but is regulated by insulin in both obese and non
      obese patients.

PMID- 7511138
TI  - Cocaine babies: does prenatal exposure to cocaine affect development?

PMID- 7511137
TI  - Temporal response of rabbits to beta-adrenergic agonist feeding: tissue weight,
      calpains and calpastatin activities, and nucleic acid and protein concentrations.
AB  - Forty-eight crossbred rabbits were used in three replications of a 2 x 4
      factorial arrangement to investigate the short-term responses of tissue
      accretion, calpains and calpastatin activity, and nucleic acid and protein
      concentrations to beta-adrenergic agonist (BAA) feeding. Rabbits were fed a 17%
      CP diet with or without 7 ppm of L644,969 and slaughtered after 1, 4, 8, or 16 d
      of treatment. Empty body dressing percentage and biceps femoris weight (as a
      percentage of empty body weight [EBW]) were significantly higher in the treated
      rabbits than in the controls after 16 d of treatment. Heart and liver weights (as
      a percentage of EBW) were higher (P < .05) after 1 d and liver weight (as a
      percentage of EBW) was lower (P < .05) after 16 d in treated vs controls. Except
      for an elevation of skeletal muscle m-calpain after 16 d, BAA-supplementation did
      not affect the calpain-calpastatin system. Muscle RNA concentrations and RNA:DNA
      ratios were higher (P < .05) in treated rabbits after 1 d and remained higher
      thereafter. Protein:RNA ratios were lower (P < .01) in treated than in control
      rabbits after 4 d and remained lower throughout the trial. Muscle DNA content was
      lower after 4 d and higher after 16 d; RNA content was higher after 4, 8, and 16
      d; and protein content was higher after 16 d in treated vs control rabbits. Liver
      nucleic acid and protein concentrations were not affected by BAA
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511139
TI  - Three-year outcome of children exposed prenatally to drugs.
AB  - OBJECTIVE: To evaluate the 3-year behavioral and developmental outcome of
      children prenatally exposed to maternal substances of abuse. METHOD: Ninety-three
      children exposed prenatally to cocaine and other drugs taken by the mother during
      pregnancy (Group 1), 24 polydrug/noncocaine exposed children (Group 2), and 25
      nonexposed children (Group 3) were evaluated at 3 years of age as part of a
      longitudinal prospective study of the impact of intrauterine substance exposure
      on long-term outcome. The Stanford-Binet Intelligence Scale: Fourth Edition(SBIS)
      was administered by examiners blinded to the exposure background of the children,
      and a pediatrician performed a complete medical evaluation on all the children.
      The children's primary caregiver completed the Achenbach Child Behavior
      Checklist. Stepwise multiple regression procedures were used to determine the
      factors that best predicted 3-year growth, intelligence, and behavior. RESULTS:
      Groups 1 and 2 differed from Group 3 on head circumference. Group 1 scored lower
      than Group 3 on SBIS Verbal Reasoning. Group 2 scored Slower than Group 3 on SBIS
      Abstract/Visual Reasoning. Cocaine exposure predicted poor verbal reasoning.
      Marijuana exposure predicted poor abstract/visual reasoning. Examiner rating
      predicted intellectual outcome and caregiver ratings. Caregivers rated exposed
      children as more aggressive than nonexposed. CONCLUSION: Contrary to information
      in the popular media, not all substance-exposed children suffer the same poor
      prognosis. In fact, generalizations about the fate of drug-exposed children must
      await additional research into the outcome of the broader population of drug
      exposed children, examining the roles of maternal and environmental factors
      across a variety of geographic locations and socioeconomic levels.

PMID- 7511140
TI  - Recurrence after resection of alpha-fetoprotein-positive hepatocellular
      carcinoma.
AB  - The long-term prognosis of surgery for hepatocellular carcinoma (HCC) is not yet
      satisfactory, the main reason being the high recurrence rate. The authors report
      the results of a long-term follow-up of 308 patients with HCC who became alpha
      fetoprotein-(AFP)-negative after resection between 1975 and 1991. By March 1992,
      there was recurrence in 134 patients (43.5%). The 1-, 3-, 5- and 10-year
      recurrence rates were 9.2%, 38.8%, 54.9% and 85.0%, respectively. The 5-year
      survival rate was 49.7% for patients who had undergone a second hepatic resection
      (n = 48). Analysis of factors influencing postoperative recurrence indicated that
      patients subjected to mass survey, with a lower gamma-glutamyltransferase level,
      at an early stage of TNM classification, with a tumour of less than 5 cm, without
      tumour embolus, and with postoperative immunotherapy had a lower incidence of
      recurrence. It is concluded that the earlier the disease is diagnosed, the less
      the recurrence rate; adjuvant immunotherapy may reduce postoperative recurrence,
      and the early detection and resection of a recurrent tumour are important to
      prolonging survival further after curative resection of HCC.

PMID- 7511142
TI  - The nucleus-limited Hsr-omega-n transcript is a polyadenylated RNA with a
      regulated intranuclear turnover.
AB  - The Drosophila Hsr-omega puff, one of the largest heat shock puffs, reveals a
      very unusual gene, identified by heat shock but constitutively active in nearly
      all cell types. Surprisingly, Hsr-omega yields two transcription end-products
      with very different roles. The larger, omega-n, is a nuclear RNA with
      characteristics suggesting a new class of nuclear RNAs. Although it neither
      leaves the nucleus nor undergoes processing, omega-n RNA is polyadenylated,
      showing that polyadenylation is not limited to cytoplasmic RNA, but possibly has
      a function in the nucleus. The amount of omega-n within the nucleus is
      specifically regulated by both transcription and turnover. Heat shock and several
      other agents cause rapid increases in omega-n. A rapid return to constitutive
      levels follows withdrawal of the agents. Degradation of omega-n is inhibited by
      actinomycin D, suggesting a novel intranuclear mechanism for RNA turnover. Within
      the nucleus, some omega-n RNA is concentrated at the transcription site; however,
      most is evenly distributed over the nucleus, showing no evidence of a
      concentration gradient which might be produced by simple diffusion from the site
      of transcription. Previous studies suggested that omega-n has a novel regulatory
      role in the nucleus. The actinomycin D-sensitive degradation system makes
      possible rapid changes in the amount of omega-n, allowing the putative regulatory
      activities to reflect cellular conditions at a given time. Omega-n differs from
      the best studied nuclear RNAs, snRNAs, in many ways. Omega-n demonstrates the
      existence of intranuclear mechanisms for RNA turnover and localization that may
      be used by a new class of nuclear RNAs.

PMID- 7511141
TI  - Anti-tumor antibody BR96 blocks cell migration and binds to a lysosomal membrane
      glycoprotein on cell surface microspikes and ruffled membranes.
AB  - BR 96 is an internalizing antibody that binds to Lewis Y (Le(y)), a carbohydrate
      determinant expressed at high levels on many human carcinomas (Hellstrom, I., H.
      J. Garrigues, U. Garrigues, and K. E. Hellstrom. 1990. Cancer Res. 50:2183-2190).
      Breast carcinoma cell lines grown to confluence bind less BR96 than subconfluent
      cultures (Garrigues, J., U. Garrigues, I. Hellstrom, and K. E. Hellstrom. 1993.
      Am. J. Path. 142:607-622). However, when the confluent cells are induced to
      migrate by scratch wounding, they again bind BR96 suggesting that antigens
      bearing the Le(y) determinant may promote cell migration. In the present study,
      BR96 was found to be highly enriched on microspikes and ruffled membranes, cell
      surface structures involved in cell migration. In addition, BR96 was a potent
      inhibitor of cell migration in vitro. When stationary BR96 treated cells were
      exposed to fresh culture media, membrane ruffles and microspikes developed at the
      cell margin and migration resumed. Immunogold microscopy showed that BR96
      antigens were enriched on these membrane protrusions. BR96 cell surface
      immunoprecipitation analysis of 3H-glucosamine labeled breast carcinoma cells
      identified antigens with approximate molecular weights of 135 kd (upper antigen)
      and 85 kd (lower antigen). A short amino terminal sequence (8 residues) of the
      upper antigen matched that of human lysosomal membrane glycoprotein 1 (LAMP-1).
      In addition, the upper antigen was detected on immunoblots probed with anti-LAMP
      1, and within the intracellular compartment BR96 was found predominantly in
      endosomes and lysosomes. A soluble LAMP-1/immunoglobulin fusion protein (LAMP
      1/Ig) was transiently expressed in both BR96 binding and nonbinding cell lines.
      Immunoblot analysis of LAMP-1/Ig's from the various cell lines showed that (a)
      acquisition of the BR96 epitope is probably controlled at the level of
      polylactosamine modification (e.g., fucosylation) rather than LAMP-1 gene
      expression; (b) alternate forms of LAMP-1/Ig comigrate with the lower BR96
      antigen raising the possibility that it may be a degradation product of the upper
      antigen; and (c) LAMP-1/Ig expressed in 3396 breast carcinoma cells has
      approximately 30-fold more BR96 epitopes than LAMP-1/Ig from non-tumorigenic
      mammary epithelial cells. Together these data indicate that a major BR96 antigen,
      LAMP-1, is present on unique cell surface domains involved in cell locomotion as
      well as membranes of the endocytic compartment. Altered glycosylation of LAMP-1
      expressed in transformed cells may contribute to their ability to disseminate.

PMID- 7511145
TI  - Heterogeneity in collagen biosynthesis by sprouting retinal endothelial cells.
AB  - Bovine retinal microvascular endothelial cells can display two distinct and
      reversible morphologies in culture: 'cobblestone' and 'sprouting'. The
      cobblestone morphology resembles the resting cells lining the lumen of mature
      vessels while the sprouting morphology resembles the angiogenic cells involved in
      the formation of new vessels. Retinal cells displayed some heterogeneity in the
      shape of the cells making up the cobblestone monolayer. In contrast, all cell
      lines displayed an identical sprouting morphology. We have investigated the
      synthesis of matrix macromolecules by retinal endothelial cells displaying either
      the cobblestone or the sprouting morphology. Type IV was the only collagen
      synthesised by eight different lines of early-passage (between one and six)
      cobblestone endothelial cells. Collagen types I and III were not detected in
      these cultures. In contrast, heterogeneity was observed in the types of collagen
      synthesized by four lines of early-passage cells displaying the sprouting
      morphology. That is, two lines synthesised collagen types, II, III and IV,
      whereas two other lines continued to synthesise only type IV collagen. Both
      cobblestone and sprouting cells synthesised fibronectin and thrombospondin,
      although the relative amounts of these macromolecules varied with culture
      conditions. The pattern of collagen synthesis by cobblestone cells was also
      affected by in vitro "ageing": 4/5 lines examined above passage eight synthesised
      collagen types I, III and IV. Our results indicate that there is heterogeneity in
      the sprouting phenotype displayed by retinal endothelial cells, and that this
      phenotype is not necessarily associated with the synthesis of type I collagen. We
      suggest that differences in the spectrum of matrix macromolecules synthesised by
      sprouting endothelial cells may play a role in the control of angiogenesis.

PMID- 7511146
TI  - Protection of transforming growth factor-beta 1 activity by heparin and fucoidan.
AB  - The transforming growth factor-beta (TGF-beta) family of proteins exert diverse
      and potent effects on proliferation, differentiation, and extracellular matrix
      synthesis. However, relatively little is known about the stability or processing
      of endogenous TGF-beta activity in vitro or in vivo. Our previous work indicated
      that 1) TGF-beta 1 has strong heparin-binding properties that were not previously
      recognized because of neutralization by iodination, and 2) heparin, and certain
      other polyanions, could block the binding of TGF-beta 1 to alpha 2-macroglobulin
      (alpha 2-M). The present studies investigated the influence of heparin-like
      molecules on the stability of the TGF-beta 1 signal in the pericellular
      environment. The results indicate that heparin and fucoidan, a naturally
      occurring sulfated L-fucose polymer, suppress the formation of an initial non
      covalent interaction between 125I-TGF-beta 1 and activated alpha 2-M.
      Electrophoresis of 125I-TGF-beta 1 showed that fucoidan protects TGF-beta 1 from
      proteolytic degradation by plasmin and trypsin. While plasmin caused little, if
      any, activation of latent TGF-beta derived from vascular smooth muscle cells
      (SMC), plasmin degraded acid-activated TGF-beta, and purified TGF-beta 1, and
      this degradation was inhibited by fucoidan. In vitro, heparin and fucoidan
      tripled the half-life of 125I-TGF-beta 1 and doubled the amount of cell
      associated 125I-TGF-beta 1. Consistent with this protective effect, heparin- and
      fucoidan-treated SMC demonstrated elevated levels of active, but not latent, TGF
      beta activity.

PMID- 7511147
TI  - A collaborative program for international education.
AB  - A collaborative educational program for Japanese nurses was developed, which
      merged the resources of the practice and education settings at the Massachusetts
      General Hospital (MGH) and the MGH Institute of Health Professions. Two
      concurrent programs were developed--Adult Health and Maternal-Child Health. These
      concurrent programs focused on content reflecting key areas in the realm of
      nursing practice and education in both Japan and the United States. Complementary
      clinical tours were an integral part of the program. This dyad of lecture and
      clinical experiences provided a forum to focus on issues relevant to nursing
      worldwide.

PMID- 7511144
TI  - Binding and activation of plasminogen on the surface of osteosarcoma cells.
AB  - Plasmin (Pm) is a broad action serine protease implicated in numerous
      physiological functions. In bone, Pm may play a role in growth, resorption,
      metastasis, and the activation of growth factors. The various components of the
      Pm system are known to bind and function on the cell surface of various cell
      types, but no pertinent data are available describing membrane-bound Pm or its
      zymogen, plasminogen (Pg), in either normal or neoplastic bone cells. We report
      here that Pg binds to the surface of the human osteosarcoma cell line MG-63 and
      is activated to Pm by endogenous urokinase plasminogen activator (uPA). These
      conclusions are based on experiments utilizing radiolabeled compounds and a cell
      surface proteolytic assay measuring amidolytic activity of Pm. 125I-Pg binding to
      cells was time dependent, saturable, reversible, and specific. Binding was
      characterized by a relatively low affinity (Kd approximately 0.9 microM) and a
      high capacity (approximately 7.5 x 10(6) sites/cell). The binding of 125I-Pg was
      associated with lysine binding sites of the plasminogen molecule. Activation of
      125I-Pg to 125I-Pm occurred on the cell surface and was dependent upon cell bound
      uPA, as determined by inhibitory antibodies. Binding of Pg to MG-63 monolayers
      represented approximately 80% bound specifically to the cell surface and the
      remainder to the surrounding extra-cellular matrix. Either co-incubation with uPA
      or pre-incubation with Pm resulted in increased 125I-Pg binding to osteosarcoma
      cells. Cell surface Pm proteolytic activity was confirmed by an amidolytic
      chromogenic assay. Both Pm and Pg bound to cells with Pg being activated by
      endogenous uPA. Plasmin activated on the cell surface was partially protected
      from inhibition by alpha 2-antiPm (requiring Pm lysine binding site interaction)
      but inhibited by aprotinin, (interacting directly with the Pm catalytic site).
      Resistance of cell bound Pm to alpha 2-antiPm inhibition suggests that cell
      surface proteolysis can occur in the presence of a soluble Pm inhibitor known to
      exist in the extracellular space. Based on these results, we speculate that the
      various bone physiological processes implicating Pm may occur at or near the bone
      cell surface.

PMID- 7511143
TI  - Residues within a conserved amino acid motif of domains 1 and 4 of VCAM-1 are
      required for binding to VLA-4.
AB  - Vascular cell adhesion molecule 1 (VCAM-1), a member of the Ig superfamily
      originally identified on activated endothelium, binds to the integrin very late
      antigen-4 (VLA-4), also known as alpha 4 beta 1 or CD49d/CD29, to support cell
      cell adhesion. Studies based on cell adhesion to two alternatively spliced forms
      of VCAM-1 or to chimeric molecules generated from them and intercellular adhesion
      molecule-1 (ICAM-1) have demonstrated two VLA-4 binding sites on the predominate
      form of VCAM-1. Here, we studied VLA-4-dependent adhesion of the lymphoid tumor
      cell line Ramos to cells expressing wild type and mutant forms of VCAM-1. Results
      based on domain deletion mutants demonstrated the existence and independence of
      two VLA-4-binding sites located in the first and fourth domains of VCAM-1.
      Results based on amino acid substitution mutants demonstrated that residues
      within a linear sequence of six amino acids found in both domain 1 and 4 were
      required for VLA-4 binding to either domain. Five of these amino acids represent
      a conserved motif also found in ICAM domains. We propose that integrin binding to
      these Ig-like domains depends on residues within this conserved motif.
      Specificity of integrin binding to Ig-like domains may be regulated by a set of
      nonconserved residues distinct from the conserved motif.

PMID- 7511148
TI  - Epidemic: overheaditis.
AB  - This article examines, in a humorous vein, the current use and misuse of
      overheads and overhead transparencies during speeches, lectures, and
      presentations. Graphic examples detailing ineffective applications and techniques
      are provided. A detailed plan to improve speakers' utilization and procedures is
      included.

PMID- 7511149
TI  - Serum TPS versus TPA in Egyptian bladder cancer patients.
AB  - This study included 328 cases (106 with bladder cancer, 152 with non-malignant
      urinary tract diseases and 70 healthy controls). Serum TPA was determined using
      the Prolifigen TPA IRMA kit supplied by AB Sangtec Medical, Bromma, Sweden and
      serum TPS was determined using the TPS IRMA kit supplied by Beki Diagnostics AB,
      Bromma, Sweden. The results of this study revealed that serum TPA had better
      sensitivity than serum TPS while no marked difference was found in the false
      positivity rates in the non-malignant urinary tract diseases. A correlation
      coefficient of 0.83 was found between serum TPA and TPS. No relation was found
      between either TPA or TPS and histopathological stage, grade or association of
      the tumor with bilharziasis. As regards the histopathological type of the tumor,
      serum TPS was slightly higher in squamous cell than transitional cell carcinoma
      but TPA showed no difference. In the follow-up of bladder cancer patients after
      surgery both TPA and TPS showed an excellent concordance with the clinical state
      of the patients. In conclusion, TPS does not seem to be an optimal test in
      Egyptian patients with bladder cancer but serial determinations of one of the two
      markers can be used in the follow-up of these patients after surgery.

PMID- 7511150
TI  - [Effects of "low dose" aprotinin in open heart surgery and its plasma
      concentration].
AB  - To determine the effects of "low dose" aprotinin in open heart surgery, we
      administrated it in 109 cases of CABG or prosthetic valve replacement. Patients
      in Group A (Aprotinin) received continuous infusion of aprotinin at the rate of
      6*10(5) KIU/hr from the induction of anesthesia to the start of ECC (extra
      corporeal circulation), and from the end of ECC to the end of blood stanching.
      They also received additional 5*10(5) KIU aprotinin in ECC prime volumes. 50
      patients in Group C (Control) received neither aprotinin nor placebo. Bleeding
      after ECC (Group A: 315.7 +/- 203.1 ml, Group C: 484.3 +/- 598.5 ml p < 0.01),
      the first 6 hours drainage (Group A: 273.0 +/- 210.0 ml, Group C: 404.7 +/- 243.2
      ml p < 0.01), the first 24 hours drainage (Group A: 510.2 +/- 248.0 ml, Group C:
      721 +/- 317.7 ml p < 0.01) was significantly reduced in Group A. Amounts of
      homologous blood transfusion were significantly reduced in group A. (Group A: 4.7
      +/- 5.3 units, Group C: 8.5 +/- 6.4 units p < 0.01). Among the patients with
      autologous blood transfusion, the rate of the patients without homologous
      transfusion was significantly higher in Group A (group A: 40/66 cases, Group C:
      8/33 cases p < 0.01). The ECC time and the operation time was significantly
      shorter in Group A. There were 69 patients (Group A: 40, Group C: 29) whose ECC
      time was longer than 120 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511152
TI  - Free alpha subunit of human chorionic gonadotrophin: molecular basis of
      immunologically and biologically active domains.
AB  - Immunochemical studies were undertaken to identify surface-orientated epitopes of
      the free alpha subunit of human chorionic gonadotrophin (hCG-alpha) at the amino
      acid sequence level. We investigated the molecular organization of these
      epitopes, resolved the immunological topography in terms of spatial arrangement
      of antigenic domains and related structures to functions such as subunit
      association or receptor binding. Overlapping synthetic peptides covering the
      entire amino acid sequence of hCG-alpha, an enzymatically digested hCG-alpha
      subunit, and a reduced and alkylated hCG-alpha preparation were assayed in a
      solid-phase one-site enzyme-linked immunoassay, and in a solution-phase
      competitive radioimmunoassay (RIA). The antigenic topography was mapped by
      monoclonal antibodies (MCAs) in two-site binding assays (sandwich RIA). On the
      surface of hCG-alpha, seven different epitopes (alpha 1-alpha 7), arranged in
      four spatially distinct domains, could be distinguished: A, alpha 1,2,4; B, alpha
      3,5; C, alpha 6; D, alpha 7. The peptides spanning hCG-alpha(13-18), hCG-alpha(17
      22) and hCG-alpha(33-42) appeared to contribute to the formation of epitopes
      alpha 2, alpha 4 and alpha 6 respectively. Since epitope alpha 6 is present only
      on the free non-assembled subunit of different species, we concluded that the
      region hCG-alpha(33-42), which is evolutionarily highly conserved, represents a
      subunit assembly site. All but one epitope (alpha 7) are destroyed by reducing
      and alkylating hCG-alpha. In contrast, chymotryptic digestion of hCG-alpha,
      leading to release of the heptapeptide hCG-alpha(41-47), did not affect epitope
      expression, indicating that this sequence is not involved in the formation of
      antigenic determinants. Addressing the biological properties of hCG-alpha
      epitopes by radioreceptor assay revealed that the three hCG-alpha peptides
      corresponding to epitopes alpha 2, alpha 4 and alpha 6 did not displace
      radiolabelled hCG from its receptor, whereas any of the MCAs directed against
      determinants (alpha 1-alpha 5), shared by hCG and hCG-alpha, totally inhibited
      binding. Consistent with this, the antibodies neutralized the biological activity
      of hCG in terms of testosterone production in a mouse Leydig cell in vitro
      bioassay. We therefore concluded that hormone antibody-binding sites differ from
      those of hormone receptor binding, revealing no essential congruence of
      immunologically and biologically active domains.

PMID- 7511153
TI  - Stimulation of mammogenesis and lactogenesis by recombinant bovine placental
      lactogen in steroid-primed dairy heifers.
AB  - A model of induced lactation was modified to examine the effects of bovine
      prolactin (bPRL) and bovine placental lactogen (bPL) on mammary growth and
      differentiation. Thirty-two peripubertal, non-pregnant Holstein heifers were
      given daily s.c. injections of oestradiol (0.05 mg/kg) and progesterone (0.25
      mg/kg) for 7 days to initiate mammary growth. Treatment with bromocriptine (40
      mg/3 days) reduced serum PRL concentrations to approximately 25% of pretreatment
      levels, for the duration of the study. On the day following the last steroid
      injection, groups of eight heifers were given twice daily s.c. injections of
      either saline (negative control), recombinant bPRL (rbPRL; 80 mg/day) or
      recombinant bPL (rbPL; 80 and 160 mg/day) for 7 days. At the end of this period
      (day 15), growth and differentiation of the mammary glands were assessed.
      Treatment with rbPL increased total mammary DNA above control value by 50 and 60%
      for the 80 and 160 mg/day doses respectively. However, total DNA was not
      different for the control and rbPRL-treated groups. The blood serum concentration
      of alpha-lactalbumin was measured daily throughout the study and used as an index
      of mammary differentiation. Both rbPRL and rbPL stimulated mammary
      differentiation (i.e. induction of milk synthesis), although rbPRL appeared to be
      more potent than rbPL. These results indicate that rbPL is lactogenic in vivo and
      strongly suggest that bPL is a mammary mitogen.

PMID- 7511155
TI  - The role of neuropeptides in the regulation of adrenal zona glomerulosa function:
      effects of substance P, neuropeptide Y, neurotensin, Met-enkephalin, Leu
      enkephalin and corticotrophin-releasing hormone on aldosterone secretion in the
      intact perfused rat adrenal.
AB  - A range of neuropeptides has been identified in the adrenal glands of many
      mammalian species. In many cases these peptides have been located in nerves
      supplying the adrenal cortical cells, or within clusters of chromaffin cells
      within the zona glomerulosa. The function of these neuropeptides has yet to be
      determined, but from their location within the gland it is clearly possible that
      they may have a role in the regulation of aldosterone secretion. The effects of
      Met-enkephalin, Leu-enkephalin, neuropeptide Y, substance P, corticotrophin
      releasing hormone (CRH) and neurotensin on aldosterone secretion were
      investigated using the intact perfused rat adrenal gland in situ. All the
      peptides tested, except CRH, caused a significant increase in aldosterone
      secretion over the dose range of 1 pmol to 10nmol, with a maximum response of
      about a twofold increase in secretion. Met-enkephalin, however, at a dose of 10
      nmol caused a 350% increase in aldosterone secretion, a response comparable with
      that seen in response to angiotensin II in this preparation. These results
      suggest that, while substance P, neuropeptide Y, neurotensin and Leu-enkephalin
      all have the capacity to cause modest increases in the rate of steroid secretion
      by the zona glomerulosa, these neuropeptides probably do not have a major role in
      the acute regulation of aldosterone secretion, at least under basal conditions.
      Met-enkephalin, on the other hand, was a more potent stimulus to aldosterone
      secretion, and thus may have a role in the control of aldosterone secretion.

PMID- 7511154
TI  - Over-expression of oxytocin in the testes of a transgenic mouse model.
AB  - The bovine oxytocin gene has been expressed in the testes of two independent
      transgenic mouse lines. Hybridization and RNase protection analysis showed that
      the oxytocin transgene was transcribed from the normal functional promoter in the
      Sertoli cells of the seminiferous tubules in a developmentally regulated manner.
      Immunohistochemistry indicated that both oxytocin and neurophysin epitopes were
      expressed together in the Sertoli cells at stages I-V and X-XII of the cycle of
      the seminiferous epithelium. Furthermore, analysis with high-performance liquid
      chromatography showed that there was a tenfold increase in the amount of amidated
      oxytocin present in testicular extracts from the transgenic mice. However, there
      appeared to be no detectable effect of this overproduction of hormone on
      testicular morphology or fertility parameters. A significant decrease by 50% was
      detected only in the levels of intratesticular testosterone and
      dihydrotestosterone. The results point to a local paracrine role for oxytocin in
      the modulation of Leydig cell function.

PMID- 7511156
TI  - Appropriate indications for prostatectomy in the UK--results of a consensus
      panel.
AB  - STUDY OBJECTIVE: The use of formal consensus development to determine appropriate
      indications for prostatectomy and to identify factors underlying clinical
      decisions about appropriateness is described. DESIGN: A nominal group technique
      was used. SETTINGS: The study took place in an academic research institution.
      PARTICIPANTS: The panel consisted of six urologists and three general
      practitioners. MEASUREMENTS AND MAIN RESULTS: The panel identified agreed
      indications for prostatectomy, expressed in terms of different combinations of
      type of retention, type and severity of symptoms, and level of comorbidity.
      Agreement was reached for 67% of the indications considered. For acute on chronic
      retention, surgery is indicated, regardless of symptom severity, if life
      expectancy is greater than one year. For acute or chronic retention, surgery is
      generally indicated if symptoms are severe, or if symptoms are moderate and life
      expectancy is greater than five years. For patients with neither acute nor
      chronic retention, surgery is indicated if symptoms are severe, or if these are
      moderate and life expectancy is greater than five years. For chronic or acute
      retention surgery is inappropriate if symptoms are mild and life expectancy is
      less than one year, or if there is no retention and only mild symptoms. An
      "appropriateness score" was developed. This confirmed that in general the ratings
      were internally consistent, that the panel attached little weight to mild
      symptoms, that a combination of irritative and obstructive symptoms was no more
      indicative of surgery than obstructive symptoms alone, and that the type of
      symptom was less important than the other factors considered. CONCLUSIONS: The
      results provide a basis for population based surveys of the need for
      prostatectomy.

PMID- 7511151
TI  - Expression of growth hormone-binding protein with a hydrophilic carboxyl terminus
      by the mouse placenta: studies in vivo and in vitro.
AB  - GH-binding protein (GHBP) or GH receptor is present in numerous extrahepatic
      tissues in the rodent. From mid- to late gestation in the mouse, the maternal
      serum concentration of GHBP increases 30- to 50-fold. We have investigated
      whether the placenta might synthesize GHBP and potentially contribute to this
      increase. RNA was isolated from placentas and subjected to Northern analysis
      using a cDNA probe to the shared region of GHBP and GH receptor-encoding mRNAs.
      From day 8 to day 18 of gestation, the GHBP-encoding mRNA (1.4 kb) increased 45
      fold in quantity. The GH receptor-encoding mRNA (4.2 kb) increased sixfold by day
      14 and then remained steady until day 18. These changes which were not co
      ordinated parallel reported changes in the steady-state concentrations of 1.4 and
      4.2 kb mRNAs in maternal liver, suggesting shared regulatory factors. Extracts of
      freshly isolated trophoblasts were assayed for GHBP with a radioimmunoassay
      specific for GHBP with a hydrophilic carboxyl terminus. The cytosolic content of
      immunoreactive GHBP increased fourfold from mid- to late gestation. Trophoblasts
      were isolated from placentas and cultured for 2 days on collagen gels in defined
      medium. Cultured cells were at least 90% viable and secreted mouse placental
      lactogen-II (mPL-II). Immunocytochemistry was carried out simultaneously on cells
      cultured from day 7 to day 17 of gestation using a monoclonal antibody (MAb 4.3),
      which recognizes the hydrophilic C-terminus of GHBP. Cell-localized GHBP was
      present in trophoblasts cultured for 2 days, but GHBP was not detectable by
      radioimmunoassay or by immunoprecipitation in concentrated culture media from
      cultures treated with 100 ng mouse GH/ml or 100 ng mPL-II/ml or from untreated
      cultures. RNA was isolated from cells cultured in an identical manner to those
      analysed by immunocytochemistry. Three GH receptor/GHBP mRNA species of 8, 4.2
      and 1.4 kb were observed. The quantity of 4.2 and 1.4 kb mRNAs did not change
      significantly in cultures from day 7 to day 15 of gestation but, in cultures from
      day 17 of gestation, the amount of 1.4 kb mRNA dropped significantly, while that
      of the 4.2 kb mRNA remained unchanged. GHBP- and GH receptor-encoding mRNAs are
      not co-ordinately regulated in vivo or in vitro. Although mPL-II was secreted
      into the medium by cultured trophoblasts, secretion of GHBP could not be
      detected. The culture medium may not contain the specific factors required for
      secretion of placental GHBP, or placental GHBP may not be destined for
      secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7511157
TI  - Neuronal survival is associated with 72-kDa heat shock protein expression after
      transient middle cerebral artery occlusion in the rat.
AB  - Induction of the 72-kDa heat shock protein expression is thought to protect
      neurons against the subsequent effects of ischemia. However, it is not clear
      whether the induction of 72-kDa heat shock protein expression by an ischemic
      event improves neuronal survival. To address this question, we outlined the
      temporal profile of neuronal induction and expression of the 72-kDa heat shock
      protein in a model of transient focal ischemia in the rat. Fifty two adult Wistar
      rats were subjected to middle cerebral artery occlusion of 2 h duration. At 0.5,
      3, 6, 9, 12, 24, 48, 96 and 168 h after reopening the artery, coronal brain
      sections were analyzed using both immunohistochemical methods and hematoxylin and
      eosin staining to determine the topographic and cellular distribution of the 72
      kDa heat shock protein, as well as the extent of neuronal damage.
      Immunoreactivity to the 72-kDa heat shock protein was not detected in neurons
      that were destined to become necrotic, and were located in the ischemic core of
      the brain lesions. However, 72-kDa heat shock protein expression was evident in
      morphologically intact neurons located in the peripheral zone. The earliest
      neuronal expression of 72-kDa heat shock protein was detected in animals in which
      the 2 h occlusion of the middle cerebral artery was followed by 6 h
      recirculation; the intensity of the 72-kDa heat shock protein immunoreactivity
      peaked at 48 h, and progressively disappeared 7 days after the ischemic
      reperfusion event.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511158
TI  - Amyloidoma of the gasserian ganglion as a cause of symptomatic neuralgia of the
      trigeminal nerve: report of three cases.
AB  - Three cases of symptomatic neuralgia of the trigeminal nerve due to an amyloidoma
      in the gasserian ganglion are described. The correct diagnosis was not made prior
      to histological examination of the surgical biopsy specimens. Medical history and
      clinical observation led to the diagnosis of a malignant process of the nasal
      cavities in the first patient; of an inflammatory dental focus in the second
      patient; and of multiple sclerosis in the third patient. CT findings were normal
      in cases 1 and 2; in case 3, a schwannoma was suspected from the CT appearances.
      In case 1, MRI had not been performed; in cases 2 and 3, MRI revealed a tumour
      mass which was also considered to be a schwannoma. Histologically, the tumours
      consisted of masses of amyloid deposits which had largely replaced the pre
      existing ganglionic cells and satellite cells. Electron microscopy confirmed the
      fibrillar structure of the deposits. Immunohistochemistry and immunocytochemistry
      revealed the amyloid to belong to the AL-lambda subtype.

PMID- 7511160
TI  - Influence of heparin on the chemotactic activity of human thrombin.
AB  - Chemoattractant properties of human thrombin have been studied, by
      polymorphonuclear leucocyte migration under agarose gel, in the presence of
      various sulphated macromolecules such as standard heparins, low molecular weight
      heparins, CY216, K2165, PK10169 and pentosane polysulphate. These compounds did
      not attract polymorphonuclear leucocytes within the range of concentrations used,
      whilst thrombin alone is a cytotaxin for these cells. Addition of heparins to
      thrombin led to an increase in the chemoattractant activity of this enzyme for at
      least one of the doses studied. Augmentation of the chemoattractant activity of
      thrombin by heparins was shown at concentrations equivalent to those found in
      vivo after administration of therapeutic doses of heparin. Pentosane
      polysulphate, at the studied concentrations, did not lead to a significant rise
      in the chemoattractant activity of thrombin.

PMID- 7511161
TI  - Effect of fepradinol on rat hind paw oedema induced by several inflammatory
      agents.
AB  - Fepradinol is an effective non-steroidal anti-inflammatory agent. The effect on
      rat paw oedema induced by various phlogistic agents was investigated. The
      inhibitory effect of fepradinol (25 mg kg-1, p.o.) on dextran-induced oedema was
      nearly equal to that of cyproheptadine (10 mg kg-1, p.o.). On oedema induced by
      platelet-activating factor only fepradinol (25 mg kg-1, p.o.) and phenidone (100
      mg kg-1, p.o.) clearly inhibited the inflammatory process. Both the above induced
      oedemas are thought to be unrelated to prostaglandins in the rat system and
      therefore, the anti-inflammatory activity against them is not shared by selective
      cyclo-oxygenase inhibitors. Fepradinol (25 mg kg-1, p.o.) displayed an inhibitory
      effect on the early and late stage of kaolin- and nystatin-induced oedemas in
      contrast with indomethacin (10 mg kg-1, p.o.) and piroxicam (10 mg kg-1, p.o.)
      which only inhibited the late stage. The results obtained in this study confirm
      that fepradinol is a potent anti-inflammatory agent and indicate that its
      mechanism of action is different from that of other anti-inflammatory compounds.

PMID- 7511163
TI  - 5 beta-Methyl-14 beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone and its
      corresponding N-cyclopropylmethyl analog, N-cyclopropylmethylnor-5 beta-methyl-14
      beta-(p-nitrocinnamoylamino)- 7,8-dihydromorphinone: mu-selective irreversible
      opioid antagonists.
AB  - 5 beta-Methyl-14 beta-(p-nitrocinnamoylamino)-7,8-dihydromorphinone (MET-CAMO)
      and its corresponding N-cyclopropylmethyl analog, N-cyclopropylmethylnor-5 beta
      methyl-14 beta-(p-nitrocinnamoylamino)- 7,8-dihydromorphinone (N-CPM-MET-CAMO)
      were tested in opioid receptor binding assays and in the mouse tail-flick test in
      order to characterize the affinity, selectivity and antinociceptive properties of
      these two compounds. Incubating bovine striatal membranes with either MET-CAMO or
      N-CPM-MET-CAMO produced a wash-resistant, concentration- and time-dependent
      inhibition of the binding of the mu-selective ligand, [3H]-[D
      Ala2,MePhe4,Gly(ol)5]enkephalin, but with no change in delta or kappa binding.
      Preincubating membranes with N-CPM-MET-CAMO decreased the maximum binding value
      for [3H]-[D-Ala2,MePhe4,Gly(ol)5]enkephalin binding without changing the Kd
      value. In the mouse tail-flick assay, MET-CAMO and N-CPM-MET-CAMO did not produce
      any antinociception up to a dose of 100 nmol after i.c.v. administration.
      However, pretreatment of mice with either compound produced a time- and dose
      dependent antagonism of morphine-induced antinociception. Analgesia mediated by
      delta or kappa opioids was not altered by either MET-CAMO or N-CPM-MET-CAMO at a
      dose of up to 100 nmol. The mu antagonistic effect of 1 nmol of MET-CAMO and N
      CPM-MET-CAMO appeared at 8 hr and lasted up to 72 hr, with a maximal effect at 16
      to 24 hr after i.c.v. administration. Pretreatment of mice with 1 nmol of MET
      CAMO or N-CPM-MET-CAMO, given by i.c.v. administration at -24 hr, produced a
      rightward and downward shift of dose-response line of i.c.v. morphine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7511162
TI  - Behavioral activation of neurokinin-1 agonists in relation to enzymatic
      degradation in the spinal cord.
AB  - Intrathecal (i.t.) injection of substance P (SP) induced reciprocal hindlimb
      scratching directed mainly toward the abdominal regions in mice. This behavior
      pattern appeared within the first minute after i.t. injection of SP. Similar
      behavioral effects were produced by i.t. injection of neurokinin (NK)-1 agonists,
      physalaemin (Phy) and [Sar9,Met(O2)11] SP (Sar-SP). The duration of scratching
      varied among NK-1 agonists; of the NK-1 agonists used, Phy had the most long
      lasting duration of scratching in contrast to SP that had a short duration. The
      rank order of scratching duration was Phy > Sar-SP > SP. SP was rapidly degraded
      by the solubilized enzyme extracted from the mouse spinal cord as determined by
      HPLC. Decay of the scratching response to these NK-1 agonists was parallel with
      the rate of their degradation by the solubilized enzyme. These results suggest
      that a relatively long-lasting scratching behavior induced by Phy is mainly
      attributed to the stability against peptidases in the spinal cord.

PMID- 7511164
TI  - Functional subtyping of neurokinin receptors on canine proximal colonic mucosa.
AB  - Functional subtyping of the receptors responsible for the neural and nonneural
      effects of substance P (SP) on the canine proximal colon were studied. Selective
      agonists and antagonists were used with two different in vitro preparations. The
      mucosa contained the muscularis mucosa and attendant submucosal plexuses, whereas
      the epithelium was devoid of both. We obtained the following results:
      [Sar9,Met(O2)11]SP (Sar9SP), a neurokinin-1 receptor agonist, stimulated both
      preparations; senktide, a neurokinin-3 agonist, evoked a response only on the
      mucosal preparation; [beta-Ala8]NKA4-10, a neurokinin-2 agonist, was ineffective
      on both preparations; tetrodotoxin completely inhibited the mucosal responses to
      senktide, but the inhibitory effects on Sar9SP were only partial; CP-96,345, a
      neurokinin-1-selective antagonist, inhibited both epithelial and mucosal
      responses to Sar9SP and R487 [Trp7,beta-Ala8]NKA4-10, a neurokinin-3 antagonist,
      inhibited mucosal responses to senktide. Thus, the neural effects involved both
      neurokinin-1 and neurokinin-3 receptors, whereas the nonneural effects were
      mediated by neurokinin-1 receptors alone. Neurokinin-2 receptors were
      functionally absent.

PMID- 7511159
TI  - Chemotherapy as first treatment for primary malignant non-Hodgkin's lymphoma of
      the central nervous system preliminary data.
AB  - Non-Hodgkin's lymphoma of the central nervous system (NHL-CNS) is thought to
      account for about 1% of primary brain tumours. Radiation therapy has mainly been
      applied to treat cerebral lymphoma, but the low cure rate and the lack of
      enduring response have stimulated the search for alternatives. With the aim of
      postponing radiotherapy as long as possible, we tested the efficacy of a M-BACOD
      schedule administered immediately after histological diagnosis in 14 patients.
      After two M-BACOD courses 10 (71%) patients displayed an objective response (i.e.
      were apparently tumour-free when examined by CT). In 6 (60%) M-BACOD-responsive
      patients, radiotherapy was delayed for 5 months (without recurrences after a
      follow-up ranging from 9 to 18 months). Moreover, in 3 M-BACOD-responsive
      patients, no recurrence took place (even without radiotherapy) after a follow-up
      of 6-12 months. We conclude that radiation can be postponed after chemotherapy or
      delayed until tumor recurrence.

PMID- 7511165
TI  - ATP closes a potassium and opens a cationic conductance through different
      receptors in neurons of guinea pig submucous plexus.
AB  - Intracellular recordings were made to study the actions of ATP and related
      nucleotides on neurons from the guinea pig submucous plexus. Local application of
      ATP, by pressure, induced a depolarization in most AH-type neurons, which had a
      latency of several milliseconds, lasted for about 5 sec, appeared to reverse at
      about +4 mV and occurred concomitantly with a reduction in input resistance.
      Pressure application of ATP also depolarized the S-type neurons. In most of these
      cells the depolarization had two phases: the first component resembled the
      depolarization observed in AH cells and the second component was much slower in
      onset and was longer lasting (30-90 sec). The slower component was associated
      with an increase in input resistance, reversed polarity near the potassium
      equilibrium potential and was observed in isolation in 30% of S neurons.
      Superfusion of ATP or other analogs (0.03-10 microns) induced a slow
      depolarization in most of S neurons with the following rank order of potency: 2
      methylthio-ATP > ATP > adenosine-5'-o-3-thiotriphosphate = ADP; alpha, beta
      methylene ATP and beta, gamma-methylene ATP were inactive (10-100 microM). When
      whole-cell recordings were used, fast superfusion with ATP or other analogs (3
      1000 microM) evoked, at negative membrane potentials, a rapidly desensitizing
      inward current. This current reversed polarity at about 0 mV and was much reduced
      in low extracellular sodium concentration. The rank order of potency of the used
      agonists was: ATP = adenosine-5'-o-3-thiotriphosphate = 2-methylthio-ATP > >
      alpha,beta-methylene ATP = beta,gamma-methylene ATP; adenosine, AMP or ADP (1 mM)
      were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511166
TI  - Distinct modes of inhibition by ruthenium red and ryanodine of calcium-induced
      calcium release in avian atrium.
AB  - We studied the properties of calcium-induced calcium release (CICR) and its
      regulation by inhibitors (caffeine, ryanodine, ruthenium red and procaine) in a
      multicellular atrial preparation that lacks T-tubules. CICR was elicited by
      application of brief (2-3 sec) calcium pulses (pCa 6.0-6.5). The transient
      contractions induced by these brief pulses were used to monitor the release of
      calcium from the sarcoplasmic reticulum in saponin-permeabilized chick atrial
      fibers. Prolonged (3-10 sec) calcium pulses produced contractions with a phasic
      CICR-mediated component followed by a tonic component due to direct activation of
      the myofilaments by calcium. Ryanodine (1 microM) suppressed the phasic but not
      the tonic contraction. CICR-mediated contractions are suppressed not only by
      ryanodine (IC50 = 23 nM), but also by ruthenium red (270 nM), procaine (8.1 mM)
      and millimolar caffeine. Ryanodine inhibits contractions mediated by CICR in a
      use-dependent manner, due to a strong requirement to act on the activated state
      of the calcium release channels. However, the blocking action of ryanodine does
      not require the presence of elevated myoplasmic calcium. A transient contraction
      occurs upon removal of procaine, which we attribute to unblocking of calcium
      release channels. Our previous studies of Ins(1,4,5)P3- and caffeine-induced
      calcium release together with the present work with CICR allow us to propose a
      model of SR calcium release mechanisms in avian atrial muscle in which corbular
      sarcoplasmic reticulum may participate.

PMID- 7511168
TI  - Two regions of an avian hepadnavirus RNA pregenome are required in cis for
      encapsidation.
AB  - We have constructed a series of deletion mutants spanning the genome of duck
      hepatitis B virus in order to determine which regions of the viral genome are
      required in cis for packaging of the pregenome into capsid particles. Deletion of
      sequences within either of two nonadjacent regions prevented replication of the
      mutant viral genomes expressed in a permissive avian hepatoma cell line in the
      presence of functionally active viral core and P proteins. Extraction of RNA from
      cells transfected with these replication-defective mutants showed that the
      mutants retained the capacity to be transcribed into a pregenomic-size viral RNA,
      but that these RNA species were not packaged into viral capsids. The two regions
      defined by these deletions are located 36 to 126 (region I) and 1046 to 1214
      (region II) nucleotides downstream of the 5' end of the pregenome and contain
      sequences which are required in cis for encapsidation of the duck hepatitis B
      virus pregenome.

PMID- 7511167
TI  - Role of Pr160gag-pol in mediating the selective incorporation of tRNA(Lys) into
      human immunodeficiency virus type 1 particles.
AB  - COS-7 cells transfected with human immunodeficiency virus type 1 (HIV-1) proviral
      DNA produce virus in which three tRNA species are most abundant in the viral tRNA
      population. These tRNAs have been identified through RNA sequencing techniques as
      tRNA(3Lys) the primer tRNA in HIV-1, and members of the tRNA(1,2Lys) isoacceptor
      family. These RNAs represent 60% of the low-molecular-weight RNA isolated from
      virus particles, while they represent only 6% of the low-molecular-weight RNA
      isolated from the COS cell cytoplasm. Thus, tRNA(Lys) is selectively incorporated
      into HIV-1 particles. We have measured the ratio of tRNA(3Lys) molecules to
      copies of genomic RNA in viral RNA samples and have calculated that HIV-1
      contains approximately eight molecules of tRNA(3Lys) per two copies of genomic
      RNA. We have also obtained evidence that the Pr160gag-pol precursor is involved
      in primer tRNA(3Lys) incorporation into virus. First, selective tRNA(Lys)
      incorporation and wild-type amounts of tRNA(3Lys) were maintained in a protease
      negative virus unable to process Pr55gag and Pr160gag-pol precursors, indicating
      that precursor processing was not required for primer tRNA incorporation. Second,
      viral particles containing only unprocessed Pr55gag protein did not selectively
      incorporate tRNA(Lys), while virions containing both unprocessed Pr55gag and
      Pr160gag-pol proteins demonstrated select tRNA(3Lys) packaging. Third, studies
      with a proviral mutant containing a deletion of most of the reverse transcriptase
      sequences and approximately one-third of the integrase sequence in the Pr160gag
      pol precursor resulted in the loss of selective tRNA incorporation and an
      eightfold decrease in the amount of tRNA(3Lys) per two copies of genomic RNA. We
      have also confirmed herein finding of a previous study which indicated that the
      primer binding site is not required for the selective incorporation of tRNA(Lys).

PMID- 7511170
TI  - Retrovirus recombination depends on the length of sequence identity and is not
      error prone.
AB  - Retroviruses, as a result of the presence of two identical genomic RNA molecules
      in their virions, recombine at a high rate. When nonhomologous RNA is present in
      the dimer RNA molecules, nonhomologous recombination can occur, although the rate
      is very low, only 0.1% of the rate of essentially homologous recombination (J.
      Zhang and H. M. Temin, Science 259:234-238, 1993). We found, as is found in
      naturally occurring highly oncogenic retroviruses (J. Zhang and H. M. Temin, J.
      Virol. 67:1747-1751, 1993), that the crossovers usually occur at a short region
      of sequence identity. We modified the previously studied vectors to study the
      effect of different lengths of short regions of sequence identity in the midst of
      otherwise nonidentical sequences. We found that the efficiency of recombination
      depends on the length of this sequence identity. However, the highest rate in
      such molecules remained lower than for recombination between essentially
      homologous molecules, even when there was extensive sequence identity. Junction
      sequences of the recombinants indicated that retrovirus recombination is not an
      error-prone process as was reported for human immunodeficiency virus reverse
      transcriptase by using a cell-free system (J. A. Peliska and S. J. Benkovic,
      Science 258:1112-1118, 1992).

PMID- 7511172
TI  - Duck hepatitis B virus infection of Muscovy duck hepatocytes and nature of virus
      resistance in vivo.
AB  - To test the hypothesis that in vivo resistance to hepadnavirus infection was due
      to resistance of host hepatocytes, we isolated hepatocytes from Muscovy ducklings
      and chickens, birds that have been shown to be resistant to duck hepatitis B
      virus (DHBV) infection, and attempted to infect them in vitro with virus from
      congenitally infected Pekin ducks. Chicken hepatocytes were resistant to
      infection, but we were able to infect approximately 1% of Muscovy duck
      hepatocytes in culture. Infection requires prolonged incubation with virus at 37
      degrees C. Virus spread occurs in the Muscovy cultures, resulting in 5 to 10%
      DHBV-infected hepatocytes by 3 weeks after infection. The relatively low rate of
      accumulation of DHBV DNA in infected Muscovy hepatocyte cultures is most likely
      due to inefficient spread of virus infection; in the absence of virus spread, the
      rates of DHBV replication in Pekin and Muscovy hepatocyte cultures are similar. 5
      Azacytidine treatment can induce susceptibility to DHBV infection in resistant
      primary Pekin hepatocytes but appears to have no similar effect in Muscovy
      cultures. The relatively inefficient infection of Muscovy duck hepatocytes that
      we have described may account for the absence of a detectable viremia in Muscovy
      ducklings experimentally infected with DHBV.

PMID- 7511171
TI  - Characterization of domains of herpes simplex virus type 1 glycoprotein E
      involved in Fc binding activity for immunoglobulin G aggregates.
AB  - Herpes simplex virus type 1 glycoproteins gE and gI form receptors for the Fc
      domain of immunoglobulin G (IgG) which are expressed on the surface of infected
      cells and on the virion envelope and which protect the virus from immune attack.
      Glycoprotein gE-1 is a low-affinity Fc receptor (FcR) that binds IgG aggregates,
      while gE-1 and gI-1 form a complex which serves as a higher-affinity FcR capable
      of binding IgG monomers. In this study, we describe two approaches used to map an
      Fc binding domain on gE-1 for IgG aggregates. First, we constructed nine plasmids
      encoding gE-1/gD-1 fusions proteins, each containing a large gE-1 peptide
      inserted into the ectodomain of gD-1. Fusion proteins were tested for FcR
      activity with IgG-sensitized erythrocytes in a rosetting assay. Three of the
      fusion proteins containing overlapping gE-1 peptides demonstrated FcR activity;
      the smallest peptide that retained Fc binding activity includes gE-1 amino acids
      183 to 402. These results indicate that an Fc binding domain is located between
      gE-1 amino acids 183 and 402. To more precisely map the Fc binding domain, we
      tested a panel of 21 gE-1 linker insertion mutants. Ten mutants with insertions
      between gE-1 amino acids 235 and 380 failed to bind IgG-sensitized erythrocytes,
      while each of the remaining mutants demonstrated wild-type Fc binding activity.
      Taken together, these results indicate that the region of gE-1 between amino
      acids 235 and 380 forms an FcR domain. A computer-assisted analysis of the amino
      acid sequence of gE-1 demonstrates an immunoglobulin-like domain contained within
      this region (residues 322 to 359) which shares homology with mammalian FcRs.

PMID- 7511169
TI  - Binding of the protease-sensitive form of PrP (prion protein) to sulfated
      glycosaminoglycan and congo red [corrected].
AB  - Congo red and certain sulfated glycans are potent inhibitors of protease
      resistant PrP accumulation in scrapie-infected cells. One hypothesis is that
      these inhibitors act by blocking the association between protease-resistant PrP
      and sulfated glycosaminoglycans or proteoglycans (e.g., heparan sulfate
      proteoglycan) that is observed in amyloid plaques of scrapie-infected brain
      tissue. Accordingly, we have investigated whether the apparent precursor of
      protease-resistant PrP, protease-sensitive PrP, binds to Congo red and heparin, a
      highly sulfated glycosaminoglycan with an inhibitory potency like that of heparan
      sulfate. Protease-sensitive PrP released from the surface of mouse neuroblastoma
      cells bound to heparin-agarose and Congo red-glass beads. Sucrose density
      gradient fractionation provided evidence that at least some of the PrP capable of
      binding heparin-agarose was monomeric. Free Congo red blocked PrP binding to
      heparin and vice versa, suggesting that these ligands share a common binding
      site. The relative efficacies of pentosan polysulfate, Congo red, heparin, and
      chondroitin sulfate in blocking PrP binding to heparin-agarose corresponded with
      their previously demonstrated potencies in inhibiting protease-resistant PrP
      accumulation. These results are consistent with the idea that sulfated glycans
      and Congo red inhibit protease-resistant PrP accumulation by interfering with the
      interaction of PrP with an endogenous glycosaminoglycan or proteoglycan.

PMID- 7511173
TI  - Identification of functional regions of herpes simplex virus glycoprotein gD by
      using linker-insertion mutagenesis.
AB  - Glycoprotein gD is a component of the herpes simplex virus (HSV) envelope
      essential for virus entry into susceptible cells. Previous studies using deletion
      and point mutations identified a functional domain of HSV-1 gD (gD-1) from
      residues 231 to 244. However, many of the deletion mutations had global effects
      on gD-1 structure, thus precluding assessment of the functional role of large
      portions of the protein. In this study, we constructed a large panel of linker
      insertion mutants in the genes for gD-1 and HSV-2 gD (gD-2). The object was to
      create mutations which would have only localized effects on protein structure but
      might have profound effects on gD function. The mutant proteins were expressed in
      transiently transfected L cells. Monoclonal antibodies (MAbs) were used as probes
      of gD structure. We also examined protein aggregation and appearance of the
      mutant glycoproteins on the transfected cell surface. A complementation assay
      measured the ability of the mutant proteins to rescue the infectivity of the gD
      null virus, FgD beta, in trans. Most of the mutants were recognized by one or
      more MAbs to discontinuous epitopes, were transported to the transfected cell
      surface, and rescued FgD beta virus infectivity. However, some mutants which
      retained structure were unable to complement FgD beta. These mutants were
      clustered in four regions of gD. Region III (amino acids 222 to 246) overlaps the
      region previously defined by gD-1 deletion mutants. The others, from 27 through
      43 (region I), from 125 through 161 (region II), and from 277 to 310 (region IV),
      are newly described. Region IV, immediately upstream of the transmembrane anchor
      sequence, was previously postulated to be part of a putative stalk structure.
      However, residues 277 to 300 are directly involved in gD function. The linker
      insertion mutants were useful for mapping MAb AP7, a previously ungrouped
      neutralizing MAb, and provided further information concerning other discontinuous
      epitopes. The mapping data suggest that regions I through IV are physically near
      each other in the folded structure of gD and may form a single functional domain.

PMID- 7511175
TI  - Cytokine-mediated induction of human immunodeficiency virus (HIV) expression and
      cell death in chronically infected U1 cells: do tumor necrosis factor alpha and
      gamma interferon selectively kill HIV-infected cells?
AB  - Infection with several DNA or RNA viruses induces a state of increased
      sensitivity to cell lysis mediated by tumor necrosis factor (TNF), particularly
      in the presence of gamma interferon (IFN-gamma). Infection of human cells with
      the human immunodeficiency virus (HIV) may induce a similar phenomenon. However,
      TNF and IFN-gamma are known upregulators of HIV replication, raising the question
      of the potential role of these cytokines in the selective elimination of cells
      infected with this virus. The present study demonstrates that chronically
      infected U1 cells were killed with much greater efficiency by costimulation with
      TNF-alpha and IFN-gamma than their uninfected parental cell line U937. However,
      synergistic induction of viral expression also occurred in U1 cells as a
      consequence of treatment with the two cytokines. Cell death in U1 cells was not
      caused by the massive production of virions, in that costimulation with
      glucocorticoid hormones and TNF-alpha or IFN-gamma resulted in high levels of
      virion production without cytopathicity. To investigate the nature of the
      selective cytotoxic effect observed in U1 cells costimulated with TNF-alpha plus
      IFN-gamma, a panel of uninfected cell clones was generated by limiting dilution
      of U937 cells and tested for response to TNF-alpha and/or IFN-gamma. In contrast
      to the uncloned bulk parental U937 cell line, most uninfected cell clones showed
      a very high susceptibility to being killed by TNF-alpha and IFN-gamma. Similar
      findings were obtained when both infected U1 cells and several uninfected U937
      cell clones were costimulated with an anti-Fas monoclonal antibody in the
      presence of IFN-gamma, although, unlike cells stimulated with TNF-alpha, cells
      treated with anti-Fas antibody did not express virus. Therefore, the increased
      susceptibility to cytokine-mediated lysis observed in cell lines infected with
      HIV is likely due to the selection of preexisting cell clones rather than viral
      infection.

PMID- 7511174
TI  - Adenovirus inhibition of cell translation facilitates release of virus particles
      and enhances degradation of the cytokeratin network.
AB  - Infection of animal cells by a number of viruses generally results in an array of
      metabolic defects, including inhibition of host DNA, RNA, and protein synthesis,
      and morphological alterations known as cytopathic effects. For adenovirus
      infection there is a profound loss of cell structural integrity and a marked
      inhibition of host protein synthesis, the latter generally assumed necessary to
      enhance virus production. We examined the purpose of viral inhibition of cell
      translation and found that it was related in part to cytopathic wasting of
      infected cells. We show that viral shutoff of host translation promotes
      destruction of the intermediate filament network, particularly cytokeratins which
      are proteolysed at keratins K7 and K18 by the adenovirus late-acting L3 23-kDa
      proteinase. We found that if adenovirus is prevented from inhibiting cell
      translation, the intermediate filament network remains relatively intact, keratin
      proteins are still synthesized, and cells possess an almost normal morphological
      appearance and lyse poorly, reducing the release of nascent virus particles by
      several hundredfold. Remarkably, in tissue culture cells the accumulation of late
      viral structural proteins is only marginally reduced if host translation shutoff
      does not occur. Thus, a surprising major function for adenovirus inhibition of
      cellular protein synthesis is to enhance impairment of cellular structural
      integrity, facilitating cell lysis and release of progeny adenovirus particles.

PMID- 7511177
TI  - Human immunodeficiency virus type 1 RNA expression by four chronically infected
      cell lines indicates multiple mechanisms of latency.
AB  - Recent information has suggested that posttranscriptional mechanisms, whereby
      human immunodeficiency virus type 1 (HIV-1) RNA exists as multiply spliced
      transcripts without promoting an accumulation of the larger messages, are
      responsible for maintaining a stable state of nonproductive viral expression or
      viral latency. To test the universality of these observations, we compared the
      patterns of viral RNA splicing and the frequencies of cells actually harboring
      HIV-1 RNA in four chronically HIV-1-infected cell lines (U1 [promonocytic], ACH-2
      [T lymphocytic], OM-10.1 [promyelocytic], and J1.1 [T lymphocytic]). In uninduced
      U1 and ACH-2 cultures, a high frequency of cells (approximately one in six)
      contained HIV-1 RNA but mainly as multiply spliced transcripts, again supporting
      a posttranscriptional mechanism maintaining viral latency. In sharp contrast,
      only 1 in 50 cells in uninduced OM-10.1 and J1.1 cultures contained HIV-1 RNA,
      indicating a primary transcriptional mechanism controlling viral expression in
      these cells. Furthermore, those OM-10.1 and J1.1 cells that did contain viral RNA
      were in a state of productive HIV-1 expression marked by the presence of both
      spliced and unspliced transcripts. Even though the total absence of viral RNA in
      the majority of OM-10.1 and J1.1 cells indicated a state of absolute latency,
      treatment with tumor necrosis factor alpha induced transcription of HIV-1 RNA in
      nearly 100% of the cells in all four of the chronically infected cultures. Tumor
      necrosis factor alpha induction of U1, ACH-2, and OM-10.1 cultures resulted in an
      initial accumulation of multiply spliced HIV-1 RNA followed by a transition to
      the larger unspliced viral RNA transcripts. This RNA splice transition was less
      apparent in the J1.1 cell line. These results demonstrate that host cell-specific
      transcriptional and posttranscriptional mechanisms are important factors in the
      control of HIV-1 latency.

PMID- 7511176
TI  - Studies of the conformation-dependent neutralizing epitopes of simian
      immunodeficiency virus envelope protein.
AB  - It has been shown previously that the major neutralizing epitopes in simian
      immunodeficiency virus (SIV) are discontinuous and conformation dependent and
      that the V3 loop, in contrast to that of human immunodeficiency virus (HIV) type
      1, does not by itself elicit neutralizing antibodies (K. Javaherian et al., Proc.
      Natl. Acad. Sci. USA 89:1418-1422, 1992). We now present data showing that on the
      basis of fractionation of infected macaque sera, protease digestion of the
      envelope, and binding properties of two neutralizing monoclonal antibodies to SIV
      and SIV-HIV chimeric envelope proteins, changes in V3 can disrupt the
      conformation-dependent neutralization region. The chimeric protein did not
      produce significant neutralizing antibodies against either SIV or HIV. We also
      report that neutralizing antibodies elicited by recombinant SIV envelope proteins
      of mac251 and B670 isolates cross-neutralize. Finally, we show that
      deglycosylation of the SIV envelope results in a molecule which binds neither
      soluble CD4 nor the neutralizing monoclonal antibodies being investigated here
      and does not elicit sera with a significant neutralizing titer.

PMID- 7511178
TI  - An epitope in the V1 domain of the simian immunodeficiency virus (SIV) gp120
      protein is recognized by CD8+ cytotoxic T lymphocytes from an SIV-infected rhesus
      macaque.
AB  - Cytotoxic T-lymphocyte (CTL) responses against the external envelope glycoprotein
      (gp120) of the simian immunodeficiency virus (SIV) were studied in a rhesus
      macaque infected with SIVmac/239. CD8+ T cells enriched from concanavalin A
      stimulated peripheral blood mononuclear cells lysed autologous target cells
      infected with recombinant vaccinia virus vectors expressing the SIVmac/239 or
      SIVsm/H4 envelope protein, which share approximately 80% identity in amino acid
      sequence. A CD8+ CTL line derived by limiting dilution culture of the
      concanavalin A-stimulated lymphocytes was also specific for the envelope proteins
      of both SIV isolates. Mapping studies revealed that this cell line recognized an
      epitope between amino acids 113 and 121 (CNKSETDRW) in the V1 domain of gp120.
      Amino acid substitutions are observed at positions 116 and 120 among viruses of
      the SIVsm/mac/human immunodeficiency virus type 2 group, and thus synthetic
      peptides representing these variants were tested for the ability to sensitize
      target cells for lysis by the CTL line. Autologous target cells sensitized with a
      synthetic peptide representing the SIVmac/239 sequence were efficiently killed.
      In contrast, recognition of target cells was reduced or abolished when peptides
      representing the amino acid substitutions at position 116 or 120 of other SIVmac,
      SIVsm, SIVmne, or SIVstm strains were tested. Further studies of CTL responses
      against this epitope could provide insights into mechanisms of variability within
      the gp120 V1 domain and its importance in evasion of immunity in infected or
      vaccinated monkeys.

PMID- 7511180
TI  - [Granulocyte colony-stimulating factor combination therapy of acute myeloid
      leukemia complicated with severe infection].
AB  - We report the usefulness of granulocyte-colony stimulating factor (G-CSF) for the
      treatment of severe infection with neutropenia after chemotherapy for acute
      myeloid leukemia (AML, M3). A 5-year-old boy was admitted because of the first
      relapse of AML. After 2 courses of chemotherapy, he suffered from right
      mandibular phlegmon due to Pseudomonas aeruginosa. Since various types of
      antimicrobial therapy were not effective and neutropenia was still present, we
      started to give him G-CSF (400 micrograms/m2/day, sc). After 5 days, there was
      increase in the neutrophil count and remarkable clinical improvements. There was
      no evidence of AML relapse after the G-CSF the rapy. He was given another course
      of chemotherapy and then underwent allogeneic bone marrow transplantation from
      his HLA non-identical, MLC non-reactive sister. This successful case indicates
      that we should use G-CSF for the management of neutropenic AML patients
      complicated with severe infection.

PMID- 7511179
TI  - [Complete remission during administration of rhG-CSF in acute myeloblastic
      leukemia with pneumonia].
AB  - A 54-year-old man was admitted with pneumonia and pancytopenia (WBC
      400/microliters, RBC 297 x 10(4)/microliters, Hb 10.1g/dl, Plt 5.6 x
      10(4)/microliter). Bone marrow aspiration revealed a proliferation of leukemic
      cells (61.6%) and led the diagnosis of AML (M2). Although no antileukemic agent
      had been administered previously, the combination therapy of antimicrobials and
      rhG-CSF for the infection not only improved pneumonia, but also induced a
      complete remission of AML. The short-term remission was followed by the first
      relapse of AML, in spite of the continuous administration of rhG-CSF. The
      abnormal karyotype (47, XY, +8) shown in the chromosomal analysis of the bone
      marrow cells at admission remained on the first remission. The second complete
      remission was induced by combination chemotherapy (BHAC-DMP), and the chromosomal
      analysis at this time showed a normal karyotype. These findings suggested that
      the first remission of AML in this case was caused mainly by the maturation
      induction effect of rhG-CSF on the leukemic cells, however, the possibility of
      the spontaneous remission in this case also remained.

PMID- 7511181
TI  - [Increased blood cell destruction during vigorous regeneration of bone marrow
      after CAMBO-VIP chemotherapy for non-Hodgkin's lymphoma].
AB  - Alternating non-cross-resistant chemotherapy has been induced for the treatment
      of non-Hodgkin's lymphoma (NHL) with the aim of cure, even in advanced cases. We
      formulated a new high dose regimen, CAMBO-VIP, which was a weekly treatment. They
      were administered during alternate weeks for a total period of 12 weeks. We
      obtained high response rate and prolonged disease-free survival with this
      regimen. We noticed the elevation of serum LDH level in some patients at or
      shortly after the completion of CAMBO-VIP treatment. LDH elevation was not
      associated with liver function abnormality in terms of elevation of GOT or total
      bilirubin. All of these patients were in complete or partial response with no
      evidence of tumor progression. An LDH isozyme study which was done at the time of
      LDH elevation showed elevation of both LDH1 and LDH2. Interestingly serum
      haptoglobin was undetectable in all 6 patients measured at the time of LDH
      elevation. Reticulocytosis and leukoerythroblastosis in peripheral blood were
      also observed in all of these patients. These abnormalities including LDH
      elevation returned to normal within a rather short period, usually within 1 to 3
      weeks. From these observations, it is most likely that these abnormalities were
      due to excessive blood cell destruction, which was observed in association with
      rapid recovery from myelosuppression.

PMID- 7511182
TI  - [Hematologic abnormalities in a patient with chronic myelogenous leukemia with
      advanced myelofibrosis were improved by G-CSF].
AB  - A 56-year-old woman was admitted with pyrexia, cough, and dyspnea on August 21,
      1991. Physical examination revealed anemia in the palpebral conjunctivas and
      moist rales at the right lower lung field. Neither the Liver nor spleen was
      enlarged. Examination of the peripheral blood showed a hemoglobin level of 8.1
      g/dl, a platelet count of 14.8 x 10(4)/microliters, and a white blood cell count
      of 2,800/microliters, with 7% blasts and 8% megakaryocytes. Tear drop-like
      erythrocytes, agranular neutrophils, and erythroblasts were also seen in the
      peripheral blood. Examination of the bone marrow showed 15% peroxidase positive
      blasts, and many micromegakaryocytes. Cytogenetic studies for bone marrow cells
      revealed the existence of the Philadelphia (Ph1) chromosome. Bone marrow biopsy
      showed normal cellularity with increase of megakaryocytes and advanced
      myelofibrosis. Breakpoint cluster region (bcr) rearrangement analysis using the
      peripheral blood mononuclear cells revealed M-bcr rearrangement. According to the
      Hannover classification for myeloproliferative disease, she was diagnosed as
      having CML with advanced myelofibrosis followed by CML with megakaryocytic
      increase. Since she had neutrocytopenia and severe infectious disease, she
      received a subcutaneous injection of 125 micrograms of G-CSF. Not only increase
      of the white blood cell count, but also disappearance of blasts, improvement of
      anemia, increase of the platelet count, and improvement of myelofibrosis were
      observed.

PMID- 7511183
TI  - [Early detection of pancreatic cancer by serum markers].
AB  - Serum markers such as pancreatic enzymes and tumor markers are useful for the
      diagnosis of pancreatic cancer. Among 40 cases of pancreatic cancer, elevated
      values were observed for immunoreactive elastase (IRE) in 70% and for CA19-9 in
      73%. Elevated serum IRE was observed more frequently in head cancer and
      resectable cancer, whereas elevation in CA19-9 occurred more often in body-tail
      cancer and unresectable cancer. Elevation of serum IRE and CA19-9 are useful for
      diagnosis of pancreatic cancer but it is not specific for pancreatic cancer.
      Therefore, we studied the clinical usefulness of a combination assay of various
      serum markers such as CA19-9, lipase, serum iron, amylase, albumin globulin
      ratio, tissue polypeptide antigen, immunoreactive trypsin, and CA125 using the
      logistic regression analysis. This assay showed higher sensitivity and high
      specificity for pancreatic cancer than CA19-9. This combination assay may be very
      useful for the diagnosis of pancreatic cancer.

PMID- 7511184
TI  - [Changes in C100-3, and N14 antibodies in patients with chronic hepatitis C
      treated with interferon].
AB  - In interferon therapy for chronic hepatitis type C, we assayed C100-3 and N14
      antibodies, and also determined IgM-C100-3 and IgM-N14 antibodies as well as HCV
      RNA. N14 antibody was assayed by an end point titer method. In patients
      responding to interferon therapy, C100-3 and N14 antibody titers were decreased
      and became negative. In patients irresponsive to interferon therapy, C100-3
      antibody titers were hardly changed, while N14 antibody titers were markedly
      increased. IgM-C100-3 and IgM-N14 antibody levels were significantly higher in
      the patients non-responding to interferon therapy than in those responding to
      interferon therapy. The daily assays of C100-3 and N14 antibody titers are
      considered useful in judging the effectiveness of interferon against chronic
      hepatitis type C.

PMID- 7511185
TI  - [Comparison of first and second generation anti-HCV antibody tests--with special
      reference to their discrepancy].
AB  - Among anti-HCV antibody tests, we compared one first generation kit(Ortho Co.)
      and two second generation kits(Eiken Kagaku-sya, Abbott Co.). Discrepancies
      between results from the tests of the three kits were examined by conducting
      confirmatory tests including polymerase chain reaction and reviewing clinical
      data. Among 240 subjects including patients with chronic liver disease, 67.9%
      were negative to all the three kits, 19.2% were positive to all, and 12.9% showed
      discrepancies between results from the three kits. The discrepancy is caused not
      only by non-specific reactions previously known in first generation kits but also
      by the kinds of epitope and their combinations in second generation kits.

PMID- 7511186
TI  - [Narcotic analgesics. Part IV. Agonists-antagonists and total antagonists of
      opiate receptors. Perspectives for clinical use of narcotic analgesics].

PMID- 7511187
TI  - In situ hybridization analysis of rat lung alpha 1(I) and alpha 2(I) collagen
      gene expression in pulmonary fibrosis induced by endotracheal bleomycin
      injection.
AB  - BACKGROUND: Endotracheal bleomycin administration in rats and other animal
      species causes rapid development of pulmonary fibrosis, characterized by a
      transiently increased number of contractile, filament-laden parenchymal cells and
      increased lung collagen synthesis and deposition. However, the identity and
      source of the cells that actively synthesize collagen and other extracellular
      matrix and their relationship to the altered lung structure and function remain
      uncertain. EXPERIMENTAL DESIGN: In this study, the cells expressing alpha 1(I)
      and alpha 2(I) procollagen genes were identified and their localization analyzed
      in control and bleomycin-treated rat lungs at different time points, by in situ
      and Northern hybridization analyses. RESULTS: In control lungs, only a few
      scattered fibroblasts with weak expression of the alpha 1(I) procollagen gene
      were localized exclusively in the adventitia of the primary and tertiary bronchi,
      as well as major blood vessels. At day 3 after bleomycin treatment, scattered
      interstitial cells with significantly increased alpha 1(I) and alpha 2(I)
      procollagen gene expression were observed in the adventitia of bronchioles,
      terminal bronchioles, and adjacent small blood vessels. At days 7 and 14, there
      was a dramatic increase in the number of interstitial cells expressing large
      amounts of alpha 1(I) procollagen messenger RNA in these areas and extending to
      the lung parenchyma. This was followed on days 21 and 28 by significant decreases
      in procollagen gene expression and the number of cells with increased collagen
      gene expression. Most of the cells with enhanced collagen gene expression were
      arrayed in a disorganized fashion and were localized mainly around bronchioles,
      terminal bronchioles, and adjacent small blood vessels as well as in the
      irregularly distributed fibrotic foci, some submesothelial areas, and injured
      parenchyma. Northern blot analysis was consistent with the above in situ
      hybridization observation of the kinetics of collagen gene expression.
      CONCLUSIONS: The results indicate that in this rat fibrosis model, increased
      numbers of the interstitial cells with high expression of type I procollagen
      genes are derived primarily from the fibroblasts in the adventitia of
      bronchioles, terminal bronchioles, and adjacent blood vessels, as well as the
      submesothelial region. This then can result in further expansion to adjacent
      parenchyma and alveolar areas.

PMID- 7511189
TI  - Regrowth resistance in leukemia and lymphoma: the need for a new system to
      classify treatment failure and for new approaches to treatment.
AB  - Treatment failure in drug sensitive malignancies is a complex phenomenon
      resulting from both drug resistance and from the rapid regrowth of malignant
      cells ('regrowth resistance'). Attempts to overcome regrowth resistance during
      the treatment of the aggressive lymphomas by increasing the frequency of
      cytotoxic therapy appears to have failed. An alternative approach of significant
      potential would be to administer biologically active agents to directly slow the
      regrowth of neoplastic cells between courses of full dose cytotoxic therapy. To
      facilitate this approach a new system for classifying treatment failure in the
      leukemias and lymphomas is needed so that the extent of regrowth resistance and
      the effects of treatment on regrowth resistance can be directly assessed.
      Accordingly, a new classification system is proposed.

PMID- 7511188
TI  - Localization of thrombospondin and its cysteine-serine-valine-threonine-cysteine
      glycine-specific receptor in human breast carcinoma.
AB  - BACKGROUND: Thrombospondin (TSP), a cell-matrix adhesion protein, and cysteine
      serine-valine-threonine-cysteine-glycine (CSVTCG), a major TSP cell adhesive
      domain, have recently been shown to play a role in tumor cell metastasis. In this
      study we immunohistochemically localized TSP and its newly discovered CSVTCG
      specific receptor in normal, benign, and neoplastic breast tissues. EXPERIMENTAL
      DESIGN: Paraffin sections of normal, benign, and neoplastic breast tissue were
      examined immunohistochemically for the presence of TSP and its CSVTCG-specific
      receptor using the avidin-biotin complex immunoperoxidase staining procedure.
      RESULTS: Positive staining using polyclonal antibodies for TSP and its tumor cell
      adhesion receptor, isolated from a human adenocarcinoma of the lung, was observed
      in all primary breast ductal carcinomas examined (N = 11). In contrast, all
      benign lesions and normal breast tissue stained negative for TSP and its receptor
      with the exception of two fibrocystic breast samples with hyperplasia. One of the
      samples showed strong TSP staining of ductal apocrine cells, whereas the other
      showed apical receptor staining of hyperplastic ductal cells. The negatively
      staining normal and benign tissues consisted of 1 normal breast, 1 gynecomastia,
      5 fibroadenomas, and 6 fibrocystic samples. Positive staining for TSP in ductal
      carcinoma was only localized in the dense stromal collagen adjacent to tumor,
      whereas the TSP receptor localized to the tumor cells. Consistent with these
      immunohistochemical staining results was the observation that protein extracts of
      breast carcinoma cells contained receptor with no detectable TSP as revealed by
      Western blotting. Capillary endothelium was focally positive for receptor in
      regions proximal to ductal epithelium in 8 of 11 neoplastic tissues and in 6 of
      14 benign samples. CONCLUSIONS: Our results indicate that increasing expression
      of stromal TSP and the CSVTCG-specific TSP receptor in ductal epithelium
      correlates with neoplastic transformation. In addition, our results indicate that
      both malignant and benign breast tissue can stimulate surrounding capillaries to
      express the TSP receptor, whereas only carcinoma has the capacity to stimulate
      surrounding nonendothelial stromal cells, such as myofibroblasts, to secrete a
      TSP-rich matrix that may contribute to the desmoplastic stromal reaction
      characteristic of ductal carcinoma tumor. The TSP-rich matrix may then promote
      tumor cell attachment, migration, and angiogenesis, factors important in tumor
      growth. The receptor-rich capillary endothelium may promote the cell adhesive
      interactions important in tumor intravasation. Taken together the results of this
      study provide a rational basis for a role of TSP in tumor angiogenesis and
      metastasis.

PMID- 7511190
TI  - Use of cell surface antigen phenotype in guiding therapeutic decisions in chronic
      myelomonocytic leukemia.
AB  - The myelodysplastic syndromes are a heterogeneous group of hematopoietic stem
      cell diseases in which both diagnosis and prognosis are determined by cellular
      morphologic criteria. In some patients, prognosis is poor due to proliferation of
      immature cells, i.e. development of acute leukemia. An important clinical
      decision for patients with myelodysplastic syndromes is whether to treat with
      supportive care or to use cytoreductive drugs to control the proliferative
      component of these illnesses. Two cases of chronic myelomonocytic leukemia are
      presented where cell surface antigen phenotype analysis showed characteristics
      suggestive of proliferative disease and the patients were treated and obtained
      remission with cytoablative therapy. Cell surface marker analysis may be useful
      in guiding therapeutic decisions in myelodysplasia.

PMID- 7511191
TI  - Natural killer cytotoxicity and lymphocyte subpopulations in patients with acute
      leukemia.
AB  - We have studied lymphocyte subpopulations and the NK cytotoxicity of the PBMC
      from acute leukemia patients in complete remission after chemotherapy or ABMT and
      from normal donors. We have found a positive linear correlation between the
      percentage of subpopulations with CD3-CD16+, CD3-CD56+ and CD3-CD8+ phenotypes
      and the percentage of NK cytotoxicity. The slopes of the regression lines in the
      two groups of patients were lower than in normal donors, indicating a decreased
      ability of these cells to operate. The percentages of these subpopulations
      represent parameters for estimating the percentage of NK cytotoxicity both in
      normal donors and in patients with acute leukemia.

PMID- 7511192
TI  - Rapid interferon-gamma-stimulated tyrosine phosphorylation of cytosolic and
      membranal proteins in HL-60 promyelocytic cells.
AB  - The involvement of tyrosine phosphorylation in the early stages of interferon
      gamma (IFN gamma)-induced monocytic differentiation of HL-60 cells was studied.
      Immunoblotting analysis demonstrated that IFN gamma induced rapid changes in the
      tyrosine phosphorylation of several endogenous cytosolic and membranal proteins.
      The most prominent of these polypeptides was a 84 kDa protein. In membranes, the
      IFN gamma-induced phosphorylation of this protein was detectable in 5 min,
      remained elevated for 3 h and declined thereafter, while a gradual decrease in
      the phosphotyrosine content was observed in cytosols. In parallel, a 40% increase
      in the phosphotyrosine phosphatase activity was detected in the later stages of
      IFN gamma treatment. Rapid changes in tyrosine phosphorylation were detected also
      in a 64 kDa protein. In contrast, 2-day exposure to IFN gamma was needed to
      potentiate significantly the tyrosine phosphorylation of a 36 kDa membranal
      polypeptide. These data support the involvement of tyrosine phosphorylation in
      the early stages of IFN gamma-induced monocytic differentiation of HL-60 cells.

PMID- 7511194
TI  - Significance of NS3 and NS5 antigens in screening for HCV antibody.

PMID- 7511195
TI  - Significance of NS3 and NS5 antigens in screening for HCV antibody.

PMID- 7511196
TI  - Significance of NS3 and NS5 antigens in screening for HCV antibody.

PMID- 7511193
TI  - Effect of herbimycin A, an inhibitor of tyrosine kinase, on protein tyrosine
      kinase activity and phosphotyrosyl proteins of Ph1-positive leukemia cells.
AB  - Herbimycin A, a benzoquinonoid anasamycin antibiotic, preferentially inhibited
      the in vitro growth of Ph1-positive leukemia cell lines. On the other hand,
      genistein, which was developed as an inhibitor of receptor-type tyrosine kinase,
      and other protein kinase inhibitors showed no selective inhibition of Ph1
      positive leukemia cell growth. Herbimycin A also displayed an abrogative effect
      on the transformation of murine hematopoietic cells by transfection with a
      bcr/abl oncoprotein-expressing retroviral vector. The antitumor action of
      herbimycin A on Ph1-positive leukemia cells is related to an inhibition of
      activity of bcr/abl protein tyrosine kinase and a subsequent reduction of the
      constitutive phosphotyrosyl proteins, however, the antibiotic has no effect on
      the expression of bcr/abl mRNA and oncoprotein. Therefore, herbimycin A may
      provide an important insight into the oncogenic action of bcr/abl oncoprotein and
      the future development of oncoprotein-targeted therapeutic agents.

PMID- 7511197
TI  - Peripheral neurotoxicity with tacrolimus.

PMID- 7511198
TI  - Estradiol-17 beta regulates the induction of VCAM-1 mRNA expression by
      interleukin-1 beta in human umbilical vein endothelial cells.
AB  - We examined the effect of estradiol-17 beta on the expression of vascular cell
      adhesion molecule-1 (VCAM-1), an adhesion molecule, in human umbilical vascular
      endothelial cells. After preincubation with estradiol-17 beta for 24 hours, cells
      were treated for 4 h with 0.5 micrograms/ml recombinant human interleukin-1 beta.
      The RNase protection assay was performed using an [alpha-32P]-labeled 121 base
      pair VCAM-1 cRNA probe. Preincubation with estradiol-17 beta (250 or 500 pg/ml)
      suppressed the induction of VCAM-1 mRNA expression by interleukin-1 beta. VCAM-1
      staining with a monoclonal antibody decreased when cells were incubated with
      estradiol-17 beta at 250 and 500 pg/ml, while staining was detectable when cells
      were treated with interleukin-1 beta at 0.5 micrograms/ml. In conclusion,
      estradiol-17 beta regulates the induction of VCAM-1 gene expression by
      interleukin-1 beta in human umbilical vein endothelial cells.

PMID- 7511199
TI  - Effects of long-lasting voluntary running on the cerebral levels of dopamine,
      serotonin and their metabolites in the spontaneously hypertensive rat.
AB  - The brain regional dopamine (DA) and serotonin (5-HT) levels and turnover were
      studied in the spontaneously hypertensive rat (SHR), following voluntary, long
      lasting (7 weeks) wheel-running exercise. Groups of rats were sacrificed 1-2 h,
      23-24 h or 47-48 h after termination of the last running session, and the
      cerebral tissue levels of 5-HT, 5-HIAA, DA and DOPAC were determined and compared
      to corresponding levels obtained in sedentary controls. In the exercised animals,
      there was a selective decrease in the limbic forebrain levels of DOPAC in the
      immediate post-exercise period (1-2 h), while the DA turnover (DOPAC/DA ratio)
      was not altered. In addition, the 5-HT and 5-HIAA levels in the serotoninergic
      nerve terminal limbic forebrain and the 5-HT turnover (5-HIAA/5-HT ratio) in the
      cell body-containing brain stem areas were decreased in the immediate post
      exercise period. No significant changes in the DA, DOPAC, 5-HT or 5-HIAA levels,
      nor in the DA and 5-HT turnover, were obtained in the remainder of the brain
      regions analyzed, regardless of time after termination of running. Taken
      together, the present study indicates that voluntary exercise in the SHR gives
      rise to differentiated regional effects on brain DA and 5-HT levels and turnover,
      thus supporting the view that changes in central monoaminergic activity are
      involved in the functional effects of long-term exercise. Interestingly, the
      psychomotor-associated limbic forebrain areas appeared particularly susceptible.

PMID- 7511201
TI  - Spinal co-administration of peptide substance P antagonist increases
      antinociceptive effect of the opioid peptide biphalin.
AB  - Intrathecal injection of 0.25 micrograms of undecapeptide substance P antagonist
      (SPA) produced transient antinociception with a peak effect at 5 min. Increasing
      the SPA dose resulted in neurotoxicity. Intrathecal injection of the opioid
      peptide biphalin (BIP) produced antinociception for over 3 hrs without
      neurotoxicity. Co-administration of SPA (at subtoxic doses) increased BIP's
      antinociceptive effect. Naltrexone reversed analgesia due to BIP alone as well as
      after BIP+SPA.

PMID- 7511202
TI  - The impact of obesity, fat distribution, and energy restriction on insulin-like
      growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone.
AB  - The aim of this study was to characterize the association between serum insulin
      like growth factor-1 (IGF-1) and obesity, as well as fat distribution, before and
      during moderate energy restriction (1,200 kcal/d). In 51 females and nine males
      having a body mass index (BMI) between 27 and 39 kg/m2, relationships between
      serum IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, growth hormone (GH), blood
      glucose, and anthropometric measurements of body fat were examined. The patients
      were studied before treatment and again after 8 and 16 weeks of dieting. Visceral
      adipose tissue (AT) was estimated by anthropometric computed tomography (CT)
      calibrated equations. In females, IGF-1 was inversely associated with the
      abdominal sagittal diameter (SagD) and with the visceral AT (r = -.41, P = .006).
      No significant correlations were found between IGF-1 and BMI or other indices of
      adiposity. Weight loss caused a temporary increase in IGF-1 concentrations (P =
      .03) and continued decrements in blood glucose levels (P = .0004 at 16 weeks). A
      statistically significant inverse correlation between IGF-1 and blood glucose
      levels was present before (r = -.30, P = .02) and after 8 (r = -.37, P = .007)
      and 16 (r = .02, P = .02) weeks of dietary treatment. Both serum IGF-1 and
      insulin levels were positively correlated with serum IGFBP-3 levels (r = .34, P =
      .009 and r = .34, P = .008, respectively). We conclude that IGF-1 levels in obese
      females reflect the intraabdominal fat mass rather than obesity per se. IGF-1 and
      blood glucose levels are inversely correlated in obesity before and during energy
      restriction.

PMID- 7511200
TI  - Characterization of quinone reductase, glutathione and glutathione S-transferase
      in human myeloid cell lines: induction by 1,2-dithiole-3-thione and effects on
      hydroquinone-induced cytotoxicity.
AB  - In this study, we have characterized quinone reductase (QR), glutathione (GSH),
      glutathione S-transferase (GST) and their induction by a chemoprotector, 1,2
      dithiole-3-thione (D3T), in the human myeloid cell lines ML-1 and HL-60. In
      addition, we also examined the toxicity of hydroquinone (HQ), a benzene
      metabolite, to these two cell lines. Both of the cell lines contain a basal level
      of cellular GSH, which is similar in the two cell lines. Although ML-1 cells
      contain much higher QR specific activity than HL-60 cells, which are relatively
      QR deficient, the GST specific activity of ML-1 cells is 1.8 times less than that
      of HL-60 cells. Immunoblot experiments showed that the GST in these two cell
      lines is GST pi. In addition, HL-60 cells exhibit 4.5 times more myeloperoxidase
      specific activity than ML-1 cells. Inclusion of D3T in the cultures could induce
      significant increases in cellular GSH content and QR activity, but not GST
      activity in either cell line. Treatment with HQ caused both inhibition of cell
      proliferation and loss of cell viability in these two myeloid cell lines. HQ
      treatment also resulted in a significant depletion of cellular GSH, which
      preceded the loss of cell viability. Pretreatment of both cell lines with
      buthionine sulfoximine, an inhibitor of GSH biosynthesis, markedly increased HQ
      induced toxicity. In contrast, the presence of dicumarol, a QR inhibitor, failed
      to potentiate HQ-induced toxicity in ML-1 cells. On the other hand, pretreatment
      of these two myeloid cell lines with D3T significantly protected against HQ
      induced inhibition of cell proliferation and cell death. Therefore, the above
      results suggest that GSH but not QR is an important factor involved in the
      toxicodynamics of HQ in these myeloid cells.

PMID- 7511203
TI  - Thin-layer chromatography of glycosphingolipids.

PMID- 7511204
TI  - The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded
      RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat
      family of proteins.
AB  - PKR is a serine/threonine protein kinase induced by interferon treatment and
      activated by double-stranded RNAs. As a result of activation, PKR becomes
      autophosphorylated and catalyzes phosphorylation of the alpha subunit of protein
      synthesis eukaryotic initiation factor 2 (eIF-2). While studying the regulation
      of PKR in virus-infected cells, we found that a cellular 58-kDa protein (P58) was
      recruited by influenza virus to downregulate PKR and thus avoid the kinase's
      deleterious effects on viral protein synthesis and replication. We now report on
      the cloning, sequencing, expression, and structural analysis of the P58 PKR
      inhibitor, a 504-amino-acid hydrophilic protein. P58, expressed as a histidine
      fusion protein in Escherichia coli, blocked both the autophosphorylation of PKR
      and phosphorylation of the alpha subunit of eIF-2. Western blot (immunoblot)
      analysis showed that P58 is present not only in bovine cells but also in human,
      monkey, and mouse cells, suggesting the protein is highly conserved. Computer
      analysis revealed that P58 contains regions of homology to the DnaJ family of
      proteins and a much lesser degree of similarity to the PKR natural substrate, eIF
      2 alpha. Finally, P58 contains nine tandemly arranged 34-amino-acid repeats,
      demonstrating that the PKR inhibitor is a member of the tetratricopeptide repeat
      family of proteins, the only member identified thus far with a known biochemical
      function.

PMID- 7511205
TI  - Activation of the Ras/mitogen-activated protein kinase signaling pathway alone is
      not sufficient to induce glucose uptake in 3T3-L1 adipocytes.
AB  - The signal transduction pathway by which insulin stimulates glucose transport is
      largely unknown, but a role for tyrosine and serine/threonine kinases has been
      proposed. Since mitogen-activated protein (MAP) kinase is activated by insulin
      through phosphorylation on both tyrosine and threonine residues, we investigated
      whether MAP kinase and its upstream regulator, p21ras, are involved in insulin
      mediated glucose transport. We did this by examining the time- and dose-dependent
      stimulation of glucose uptake in relation to the activation of Ras-GTP formation
      and MAP kinase by thrombin, epidermal growth factor (EGF), and insulin in 3T3-L1
      adipocytes. Ras-GTP formation was stimulated transiently by all three agonists,
      with a peak at 5 to 10 min. Thrombin induced a second peak at approximately 30
      min. The activation of p21ras was paralleled by both the phosphorylation and the
      activation of MAP kinase: transient for insulin and EGF and biphasic for
      thrombin. However, despite the strong activation of Ras-GTP formation and MAP
      kinase by EGF and thrombin, glucose uptake was not stimulated by these agonists,
      in contrast to the eightfold stimulation of 2-deoxy-D-[14C]glucose uptake by
      insulin. In addition, insulin-mediated glucose transport was not potentiated by
      thrombin or EGF. Although these results cannot exclude the possibility that
      p21ras and/or MAP kinase is needed in conjunction with other signaling molecules
      that are activated by insulin and not by thrombin or EGF, they show that the
      Ras/MAP kinase signaling pathway alone is not sufficient to induce insulin
      mediated glucose transport.

PMID- 7511206
TI  - Expression of the plasmodial pfmdr1 gene in mammalian cells is associated with
      increased susceptibility to chloroquine.
AB  - Chloroquine (CQ)-resistant (CQR) Plasmodium falciparum malaria parasites show a
      strong decrease in CQ accumulation in comparison with chloroquine-sensitive
      parasites. Controversy exists over the role of the plasmodial pfmdr1 gene in the
      CQR phenotype. pfmdr1 is a member of the superfamily of ATP-binding cassette
      transporters. Other members of this family are the mammalian multidrug resistance
      genes and the CFTR gene. We have expressed the pfmdr1-encoded protein, Pgh1, in
      CHO cells and Xenopus oocytes. CHO cells expressing the Pgh1 protein demonstrated
      an increased, verapamil-insensitive susceptibility to CQ. Conversely, no increase
      in drug susceptibility to primaquine, quinine, adriamycin, or colchicine was
      observed in Pgh1-expressing cells. CQ uptake experiments revealed an increased,
      ATP-dependent accumulation of CQ in Pgh1-expressing cells over the level in
      nonexpressing control cells. The increased CQ accumulation in Pgh1-expressing
      cells coincided with an enhanced in vivo inhibition of lysosomal alpha
      galactosidase by CQ. CHO cells expressing Pgh1 carrying two of the CQR-associated
      Pgh1 amino acid changes (S1034C and N1042D) did not display an increased CQ
      sensitivity. Immunofluorescence experiments revealed an intracellular
      localization of both mutant and wild-type forms of Pgh1. We conclude from our
      results that wild-type Pgh1 protein can mediate an increased intracellular
      accumulation of CQ and that this function is impaired in CQR-associated mutant
      forms of the protein. We speculate that the Pgh1 protein plays an important role
      in CQ import in CQ-sensitive malaria parasites.

PMID- 7511207
TI  - Loss of p53 protein during radiation transformation of primary human mammary
      epithelial cells.
AB  - The causative factors leading to breast cancer are largely unknown. Increased
      incidence of breast cancer following diagnostic or therapeutic radiation suggests
      that radiation may contribute to mammary oncogenesis. This report describes the
      in vitro neoplastic transformation of a normal human mammary epithelial cell
      strain, 76N, by fractionated gamma-irradiation at a clinically used dose (30 Gy).
      The transformed cells (76R-30) were immortal, had reduced growth factor
      requirements, and produced tumors in nude mice. Remarkably, the 76R-30 cells
      completely lacked the p53 tumor suppressor protein. Loss of p53 was due to
      deletion of the gene on one allele and a 26-bp deletion within the third intron
      on the second allele which resulted in abnormal splicing out of either the third
      or fourth exon from the mRNA. PCR with a mutation-specific primer showed that
      intron 3 mutation was present in irradiated cells before selection for immortal
      phenotype. 76R-30 cells did not exhibit G1 arrest in response to radiation,
      indicating a loss of p53-mediated function. Expression of the wild-type p53 gene
      in 76R-30 cells led to their growth inhibition. Thus, loss of p53 protein appears
      to have contributed to neoplastic transformation of these cells. This unique
      model should facilitate analyses of molecular mechanisms of radiation-induced
      breast cancer and allow identification of p53-regulated cellular genes in breast
      cells.

PMID- 7511208
TI  - Molecular genetic analyses of a 376-kilodalton Golgi complex membrane protein
      (giantin)
AB  - Molecular genetic analyses of a 376-kDa Golgi complex (GC) membrane protein
      (giantin) are described. The immunoglobulin G fraction of a human serum
      containing antibodies against GC antigens as revealed by indirect
      immunofluorescence microscopy with Hep-2 cells was used to screen a HeLa cDNA
      expression library, yielding four overlapping cross-hybridizing clones.
      Additional cDNA clones were retrieved from a lambda gt11 human thyroid cDNA
      library or generated by reverse transcriptase-mediated PCR from HeLa cell mRNA.
      Alignment of the clones resulted in a consensus cDNA of 10,300 bp encoding a
      protein of 376 kDa. The corresponding mRNA with a size of about 10 kb was
      detected by Northern (RNA) blotting of HeLa, Hep-G2, and Jurkat cell RNA.
      Sequence analyses of the protein revealed an extraordinarily high content of
      heptad repeats with the probability of forming coiled coils similar to the
      proteins of the myosin family. Five overlapping recombinant proteins covering the
      entire sequence were synthesized and used for antibody production in rabbits and
      for affinity purification of human and rabbit antibodies. Indirect
      immunofluorescence experiments also done with brefeldin A-treated Hep-2 and Pt K1
      cells revealed an identical GC staining of both the affinity-purified human and
      rabbit antibodies. Double labeling experiments with antibodies against the GC
      marker mannosidase II as well as immunoelectron microscopic studies confirmed the
      localization of the protein within the GC. A corresponding endogenous large
      molecular-mass protein of about 390 kDa was found in [35S]methionine-labeled Hep
      2 cell lysates as well as in GC-enriched subcellular fractions from rat liver.
      The protein as well as the recently described proteins golgin-95 and golgin-160
      (M. J. Fritzler, J. C. Hamel, R. L. Ochs, and E. K. L. Chan, J. Exp. Med. 178:49
      62, 1993) may belong to a new group of Golgi proteins with a high content of
      heptad repeats which may exert functions in scaffold formation or vesicle
      transport. As far as can be concluded from immunological and personally
      communicated partial cDNA sequence data, the protein seems to be identical with a
      400-kDa Golgi protein (giantin) recently described (A. D. Linstedt and H. P.
      Hauri, Mol. Biol. Cell 4:679-693, 1993). Therefore, we agreed to adopt the name
      giantin.

PMID- 7511211
TI  - Sequence analysis and fine specificity of two human monoclonal antibodies to
      histone H1.
AB  - Two human IgM lambda monoclonal antibodies (MAb) derived from the splenic
      lymphocytes of patients with idiopathic thrombocytopenia (Ben) and systemic lupus
      erythematosus (Wri) were studied. BEN-27 and WRI-170 hybridoma supernatants were
      screened for binding to ssDNA, dsDNA, poly (ADP-ribose), cardiolipin, histone
      subclasses and Klebsiella K30 cell wall antigen. Of this panel of antigens, BEN
      27 and WRI-170 antibodies reacted only with histone H1. Their fine specificity
      was defined by direct and inhibition ELISA with synthetic peptides of the major
      human H1b variant. Antibody WRI-170 was shown to bind to both the N- and C
      terminal peptides encompassing residues 1-16 and 204-218 of H1b whereas BEN-27
      reacted only with peptide 204-218. To analyse the genetic origin of these
      autoantibodies, we determined the nucleotide sequence of the heavy (H) and light
      (L) chain variable regions of these two hybridomas. BEN-27 and WRI-170 MAbs were
      found to use VH1-DN1-JH4/V lambda 3-J lambda 2 and VH3-DIR2-D21/9-JH1/V lambda 2
      J lambda 2 gene segment combinations respectively. Between 70 and 95% homology
      was demonstrated when the mRNA sequences for BEN-27 and WRI-170 were compared
      with published VH and V lambda germline sequences. This finding suggests that BEN
      27 heavy and light chains and WRI-170 light chain use unidentified VH and V
      lambda germline gene segments whereas WRI-170 heavy chain derives from a VH gene
      segment recently identified. It is noteworthy that the CDRs of the two MAbs
      contain several negatively charged amino acids which are assumed to be of
      critical importance in antigen binding. Moreover, striking similarities are
      observed between BEN-27 heavy chain CDR2 and a previously described murine anti
      H1 Ab heavy chain CDR2.

PMID- 7511212
TI  - Analysis of antibody-antigen and antibody-anti-(idiotypic antibody) cross
      reactivity using synthetic peptide probes.
AB  - The extent, nature and structural basis of immunological cross-reactivity of an
      anti-synthetic peptide monoclonal antibody (MAb) with the parent antigen
      (influenza virus haemagglutinin) from which the peptide was derived, and with a
      paratope-directed anti-idiotypic (anti-Id) antibody was investigated. Use of
      synthetic homologs and analogs of the peptide indicated that the anti-peptide MAb
      utilizes a common binding site to complex with peptide, haemagglutinin (HA) and
      anti-Id antibody, and the affinity constants for the binding of the anti-peptide
      MAb to peptide and to the anti-Id MAb were found to differ only by three fold.
      Determination of the amino acid sequence of the heavy chain variable domain (VH)
      of the anti-Id MAb did not reveal any obvious sequence homology with the peptide.
      Consideration of the spatial arrangement of residues, however, disclosed a region
      within the framework of the anti-Id VH with similarity to the epitope recognized
      by the anti-peptide MAb. This region, formed from antiparallel chains, contains
      amino acid residues arranged in a conformation similar to that assumed by amino
      acid residues comprising the epitope within the intact HA.

PMID- 7511209
TI  - The human beta 2 integrin CD18 promoter consists of two inverted Ets cis
      elements.
AB  - To define the minimal promoter responsible for expression of CD18 in myeloid and
      lymphoid cells, we generated 5' and 3' deletion constructs of a segment extending
      785 bp upstream and 19 bp downstream of a major transcription start site and
      determined their effects on driving expression of the luciferase reporter gene in
      transfected hematopoietic cell lines. A region extending from nucleotides (nt) 
      302 to +19 was sufficient for cell-restricted and phorbol ester-inducible
      expression. DNase I footprinting of this region revealed two adjacent protected
      segments extending from nt -81 to -68 (box A) and -55 to -41 (box B). When a
      construct of 47 nt in length containing box A and box B and lacking other 3' or
      5' elements was cloned into a promoterless vector, it conferred tissue-specific
      and phorbol ester-inducible expression. Gel retardation revealed that the protein
      components of two major protein-DNA complexes that form on both box A and box B
      and are required for transcriptional activation are members of the Ets
      oncoprotein family; one is related to the GA-binding protein (GABP), and the
      other is related to PU.1/Spi-1. The minimal CD18 promoter, lacking TATA, CAAT,
      and initiator elements and consisting primarily of Ets repeats, may exemplify an
      emerging class of promoters with which the concerted binding of Ets factors is
      necessary and sufficient to mediate transcriptional activation through direct
      recruitment of the basal transcription machinery.

PMID- 7511210
TI  - Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP,
      SHC, Syk, and Vav.
AB  - Src homology 2 (SH2) domains provide specificity to intracellular signaling by
      binding to specific phosphotyrosine (phospho-Tyr)-containing sequences. We
      recently developed a technique using a degenerate phosphopeptide library to
      predict the specificity of individual SH2 domains (src family members, Abl, Nck,
      Sem5, phospholipase C-gamma, p85 subunit of phosphatidylinositol-3-kinase, and
      SHPTP2 (Z. Songyang, S. E. Shoelson, M. Chaudhuri, G. Gish, T. Pawson, W. G.
      Haser, F. King, T. Roberts, S. Ratnofsky, R. J. Lechleider, B. G. Neel, R. B.
      Birge, J. E. Fajardo, M. M. Chou, H. Hanafusa, B. Schaffhausen, and L. C.
      Cantley, Cell 72:767-778, 1993). We report here the optimal recognition motifs
      for SH2 domains from GRB-2, Drk, Csk, Vav, fps/fes, SHC, Syk (carboxy-terminal
      SH2), 3BP2, and HCP (amino-terminal SH2 domain, also called PTP1C and SHPTP1). As
      predicted, SH2 domains from proteins that fall into group I on the basis of a Phe
      or Tyr at the beta D5 position (GRB-2, 3BP2, Csk, fps/fes, Syk C-terminal SH2)
      select phosphopeptides with the general motif phospho-Tyr-hydrophilic (residue)
      hydrophilic (residue)-hydrophobic (residue). The SH2 domains of SHC and HCP
      (group III proteins with Ile, Leu, of Cys at the beta D5 position) selected the
      general motif phospho-Tyr-hydrophobic-Xxx-hydrophobic, also as predicted. Vav,
      which has a Thr at the beta D5 position, selected phospho-Tyr-Met-Glu-Pro as the
      optimal motif. Each SH2 domain selected a unique optimal motif distinct from
      motifs previously determined for other SH2 domains. These motifs are used to
      predict potential sites in signaling proteins for interaction with specific SH2
      domain-containing proteins. The Syk SH2 domain is predicted to bind to Tyr
      hydrophilic-hydrophilic-Leu/Ile motifs like those repeated at 10-residue
      intervals in T- and B-cell receptor-associated proteins. SHC is predicted to bind
      to a subgroup og these same motifs. A structural basis for the association of Csk
      with Src family members is also suggested from these studies.

PMID- 7511213
TI  - The syndrome of painful legs and moving toes.
AB  - The clinical presentation, symptoms, and signs in 20 new patients with the
      painful legs and moving toes syndrome are presented. Painful legs and moving toes
      may develop in the setting of spinal cord and cauda equina trauma, lumbar root
      lesions, injuries to bony or soft tissues of the feet, and peripheral neuropathy.
      In 4 of the 20 cases in the present study, no definite cause was found. Pain
      preceded the onset of toe movements in 18 cases, but in 2 the reverse sequence
      occurred. The pain had many of the characteristics of causalgia, but none of the
      patients exhibited the full picture of reflex sympathetic dystrophy, and
      peripheral trauma was the trigger in only 5 cases. Several patients reported that
      the occurrence of toe movements was closely related to the pain, although
      abolition of pain with lumbar sympathetic blocks was not necessarily associated
      with disappearance of the movements. Several features suggest a central origin
      for the movements. Symptoms may begin on one side and become bilateral; movements
      may be momentarily suppressed by voluntary action or exacerbated by changing
      posture; and electromyography reveals complex patterns of rhythmic activity with
      normal recruitment of motor units involving several myotomes. Three other
      patients with similar moving toes but no pain are also described. The occurrence
      of similar movements in the absence of pain raises the possibility that these
      cases represent examples at one end of a spectrum of disorders, with pain alone
      (causalgia) at the other end and the syndrome of painful legs and moving toes in
      between.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511215
TI  - A single amino acid determines the specificity of a monoclonal antibody which
      inhibits Plasmodium chabaudi AS in vivo.
AB  - The in vivo inhibitory action of NIMP23, a monoclonal antibody raised against the
      rodent parasite Plasmodium chabaudi chabaudi AS, has previously been shown to be
      strain-specific, capable of delaying significantly the onset of P. c. chabaudi AS
      but not a P. c. chabaudi CB challenge parasitaemia. The epitope to which this mAb
      binds has been mapped to the second of two epidermal growth factor-like domains
      located at the C-terminus of the merozoite surface protein 1 (MSP-1) of P. c.
      chabaudi AS. The C-terminus region of the MSP-1 of P. c. chabaudi is a region of
      heterogeneity with AS and CB strain parasites showing only 78% identity at the
      amino acid level. The critical amino acid substitution which accounts for the
      strain specificity of the NIMP23 monoclonal antibody has now been identified.
      Polymerase chain reaction directed mutagenesis experiments demonstrate that a
      single proline to asparagine substitution at position 1722 in the primary amino
      acid sequence is sufficient to convert NIMP23-negative P. c. chabaudi CB
      expression constructs into NIMP23-positive clones whilst the converse
      substitution of an asparagine for a proline residue converts P. c. chabaudi AS
      expression constructs into NIMP23-negative clones.

PMID- 7511216
TI  - Roche loses round in interferon patent battle.

PMID- 7511214
TI  - Nucleotide sequence analysis and epitope mapping of the merozoite surface protein
      1 from Plasmodium chabaudi chabaudi AS.
AB  - The complete nucleotide sequence of the gene encoding the merozoite surface
      protein 1 (MSP-1) from the rodent malaria parasite Plasmodium chabaudi chabaudi
      AS has been determined by direct sequencing of overlapping PCR derived fragments.
      Comparison of the P. c. chabaudi AS nucleotide sequence with the previously
      published P. c. chabaudi IP-PC1 sequence indicates that although the MSP-1 gene
      of these two P. c. chabaudi strains is highly conserved, with sequence identity
      often approaching 100%, interspersed throughout the molecule are 5 regions of
      divergence. This is at variance with published data which suggested that the P.
      c. chabaudi AS and P. c. chabaudi IP-PC1 MSP-1 sequences are largely identical.
      Epitope mapping studies with a panel of anti-P. c. chabaudi AS MSP-1 monoclonal
      antibodies demonstrate that whilst most of these mAbs recognise epitopes at the N
      terminus of the MSP-1 molecule, two mAbs, including one capable of inhibiting
      challenge infections in mice in an in vivo passive transfer assay, recognise
      epitopes which map to the C-terminus.

PMID- 7511217
TI  - Direct modulation by Ca(2+)-calmodulin of cyclic nucleotide-activated channel of
      rat olfactory receptor neurons.
AB  - Olfactory receptor neurons depolarize in response to odorant stimulation of their
      sensory cilia. One transduction mechanism involves a G-protein-mediated increase
      in adenylate cyclase activity, raising the internal cyclic AMP concentration to
      open a cyclic nucleotide-activated cation channel on the plasma membrane. An
      influx of Ca2+ through this channel, which is permeable to both monovalent and
      divalent cations, triggers olfactory adaptation. Previous work has indicated that
      at least part of this Ca(2+)-mediated adaptation resides in the channel itself,
      but the mechanism remains unclear and controversial. Here we use the cloned
      channel from rat expressed in a cell line and the native channel from rat
      olfactory receptor cells to show that Ca2+ reduces the apparent affinity of the
      channel for cAMP by up to 20-fold in the presence of calmodulin, an abundant
      protein in olfactory cilia. This decrease in apparent affinity appears to involve
      a direct interaction between Ca(2+)-calmodulin and the channel, and it can reduce
      the activation of the channel by cAMP by up to a few hundred-fold, suggesting
      that it may be a key component of the Ca(2+)-triggered olfactory adaptation.

PMID- 7511218
TI  - Overnight storage of the porcine isolated splenic artery enhances endothelium
      dependent contractions to NG-nitro-L-arginine methyl ester without impairing
      endothelium-dependent dilator function.
AB  - This study examined the influence of overnight storage on endothelium-independent
      contractions to 5-hydroxytryptamine (5-HT), endothelium-dependent contractions to
      NG-nitro-L-arginine methyl ester (L-NAME), and endothelium-dependent relaxations
      to substance P (SP) and L-arginine, using the porcine isolated splenic artery. In
      endothelium-intact (E+) segments from fresh porcine isolated splenic arteries or
      segments from the same vessels stored overnight at 4 degrees C, either in Krebs
      Henseleit saline or in Krebs-Henseleit saline containing 1 mM L-arginine, 5-HT
      caused concentration-related contractions that were similar under all three
      conditions. Overnight storage enhanced contractions of the splenic artery to L
      NAME, an effect not observed if the vessels were co-stored with 1 mM L-arginine.
      L-NAME failed to contract endothelium-denuded (E-) segments from fresh tissues or
      tissues stored overnight, indicating that its constrictor effects were
      endothelium-dependent. SP caused concentration-related, endothelium-dependent
      relaxations of the splenic artery that were inhibited by 100 microM L-NAME,
      indicating that the relaxations could be attributed to the stimulated release of
      NO from endothelial cells. Established contractions to 100 microM L-NAME in E+
      segments from fresh tissues, or segments from the same tissues stored overnight
      at 4 degrees C, either in Krebs-Henseleit saline or in Krebs-Henseleit saline
      containing 1 mM L-arginine, were all reversed by 1 mM L-arginine to similar
      extents, indicating that overnight storage did not affect endothelium-dependent
      dilator responses to L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511220
TI  - Horizontal transmission of hepatitis C virus to the spouses of patients on renal
      replacement therapy.

PMID- 7511219
TI  - Von Willebrand factor in the rat kidney: its localization and the effects of its
      in vivo interaction with specific antibodies.
AB  - Antiendothelial cell antibodies and increased von Willebrand factor (vWF) levels
      are observed in many renal diseases. We studied renal morphology after
      administration of rabbit anti-human factor VIII-von Willebrand factor (FVIII
      vWFc) gamma-globulin (IgG) in rats. Isolated perfusion of normal rat kidney with
      the antibodies disclosed rabbit IgG along glomerular endothelium and in mesangial
      areas. Systemic administration resulted in an identical antibody distribution. C3
      deposits and few electron dense deposits were transiently noted. After 1 week the
      mesangial deposition of rabbit IgG had increased significantly, most likely
      reflecting increased release of vWF by the endothelium. Thereafter, the deposits
      gradually relocated into mesangial stalk and into the glomerular vascular pole,
      and they had vanished after 6 weeks. Except for a mild influx of leukocytes, no
      renal injury occurred. In conclusion, although FVIII-vWFc antibodies cause
      mesangial immune deposits, antibodies against other endothelial antigens are
      apparently needed to inflict renal damage.

PMID- 7511221
TI  - [Anders Jahre Prize for young researchers 1993. Syndecan--a regulator of growth
      factor activities between cells and cell matrix interface].
AB  - Syndecans are a four member family of cell surface proteoglycans, which via their
      heparan sulfate chains can bind both extracellular matrix molecules and heparin
      binding growth factors. In signal transduction they cooperate with tyrosine
      kinase receptors and thus can participate in the regulation of cell growth and
      behaviour. Besides the fact that their developmental expression follows
      morphogenetic rather than histological boundaries, also changes in their
      expression take place during development of diseases. Among these, the loss of
      syndecan expression during malignant transformation suggests that syndecans could
      play a role in restricting tumor growth and metastasis.

PMID- 7511222
TI  - On the use of phasing experiments to measure helical repeat and bulge loop
      associated twist in RNA.
AB  - In a phasing experiment, two bends are introduced into a long duplex RNA or DNA
      and the number of base pairs between them varied. When electrophoresed in a gel,
      the set of molecules may show a periodic variation in mobility that contains
      information about the twist associated with the bends and the intervening helix.
      We show how a set of three phasing experiments can be used to extract this
      information, and apply it to an RNA helix bend at the bulge sequence A2. The
      bulge introduces a negative (left-handed) twist of approximately 30 degrees; at
      low temperatures, it is mostly confined to the 5' side of the bulge. The apparent
      helical repeat of random sequence RNA measured in these experiments was 10.2 +/-
      0.1 base pairs, an unexpectedly low value. It is likely that moderate curvative
      of the RNA helix axis (30-40 degrees over 80 bp) has affected the measurement.

PMID- 7511223
TI  - Pacemaker syndrome.

PMID- 7511225
TI  - Bradycardia dependent QT prolongation and ventricular fibrillation following
      catheter ablation of the atrioventricular junction with radiofrequency energy.
AB  - Recurrent ventricular fibrillation was observed in a 67-year-old woman following
      catheter ablation of the AV junction using radiofrequency energy. This serious
      complication has been reported following direct current energy ablation of the AV
      junction, but not after using radiofrequency energy. This life-threatening
      arrhythmia seemed pause and bradycardia dependent. It was followed by QTc
      prolongation of the QRS escape rhythm 1 day after the procedure. Ventricular
      arrhythmias were suppressed by rapid ventricular pacing.

PMID- 7511224
TI  - Upper rate lockout: an unexpected feature of rate adaptive atrioventricular
      delay.
AB  - We present a case in which use of rate adaptive AV delay resulted in unexpected
      pacemaker 2:1 AV block when the patient's atrial rate exceeded the pacemaker
      maximum tracking rate but was below the predicted multiblock rate. "Lockout" of
      normal upper rate behavior was accompanied with the requirement of a slower
      atrial rate for reassociation than loss of atrial tracking, a form of upper rate
      hysteresis. The mechanism of upper rate lockout is discussed, along with
      potential ways to avoid the problem. The use of software based pacemakers with an
      extended range of programmable options allows the most flexibility in optimizing
      pacemaker performance in an individual patient.

PMID- 7511227
TI  - Influence of internal current and pacing current on pacemaker longevity.
AB  - The effects of lower pulse amplitude on battery current and pacemaker longevity
      were studied comparing the new, small-sized VVI pacemaker, Minix 8341, with the
      former model, Pasys 8329. Battery current was telemetrically measured at 0.8,
      1.6, 2.5, and 5.0 V pulse amplitude and 0.05, 0.25, 0.5, and 1.0 msec pulse
      duration. Internal current was assumed to be equal to the battery current at 0.8
      V and 0.05 msec. Pacing current was calculated subtracting internal current from
      battery current. The Minix pacemaker had a significantly lower battery current
      because of a lower internal current (Minix: 4.1 +/- 0.1 microA; Pasys: 16.1 +/-
      0.1 microA); pacing current of both units was similar. At 0.5 msec pulse
      duration, the programming from 5.0-2.5 V pulse amplitude resulted in a greater
      relative reduction of battery current in the newer pacemaker (51% vs 25%).
      Projected longevity of each pacemaker was 7.9 years at 5.0 V and 0.5 msec. The
      programming from 5.0-2.5 V extended the projected longevity by 2.3 years (Pasys)
      and by 7.1 years (Minix). The longevity was negligibly longer after programming
      to 1.6 V. CONCLUSION: extension of pacemaker longevity can be achieved with the
      programming to 2.5 V or less if the connected pacemakers need a low internal
      current for their circuitry.

PMID- 7511226
TI  - NASPE Young Investigator Awardee-1993. Computer model of the atrioventricular
      node predicts reentrant arrhythmias.
AB  - INTRODUCTION: Following atrial premature beats, the AV node may exhibit sustained
      reentrant tachyarrhythmias, isolated echo beats, or discontinuities in the
      recovery curve (the plot of conduction time versus atrial cycle length). A
      computer model was used to examine the hypothesis that spatial variation of AV
      nodal passive electrical resistance may account for these phenomena. METHODS AND
      RESULTS: A computer model of a rectangular lattice of electrotonically linked
      elements whose ionic kinetics simulated nodal ionic flux was developed. The model
      showed that there exists a resistance value that minimizes the effective
      refractory period, because high resistance prevents depolarization of distal
      elements, while low resistance allows leakage of depolarizing current by
      electrotonic transmission, preventing activation of proximal elements. High
      resistances stabilized reentry by slowing conduction. Simulations incorporating
      equal resistance values between elements predicted increased AV nodal conduction
      times with increasing prematurity of atrial impulses. A model with a gradual
      change in resistance between fibers produced discontinuities and tachycardia, but
      not both simultaneously. Uniform anisotropy produced preferential transverse
      block, leading to echo beats and "fast-slow" tachycardia, but not recovery curve
      discontinuities. Nonuniform anisotropy could produce reentry, but tachycardia
      often occurred without discontinuities. Dividing the lattice into two
      electrotonically linked parallel pathways with different resistance values ("dual
      pathway model") predicted recovery curve discontinuities, echo beats, and
      tachycardia. At critical atrial cycle lengths, only the (high resistance) slow
      pathway conducted antegradely, while the fast pathway conducted retrogradely, to
      generate the typical "slow-fast" tachycardia. Responses of the dual pathway model
      to ablation were consistent with clinical data, including the previous
      observation of a decrease in fast pathway effective refractory period after slow
      pathway ablation. CONCLUSION: Differences in passive electrical resistance of
      electronically linked dual pathways within the AV node may account for functional
      longitudinal dissociation, reentrant arrhythmias, and responses to catheter
      ablation therapy.

PMID- 7511228
TI  - Performance of implantable cardiac rhythm management devices.

PMID- 7511229
TI  - Pacing system analyzers: different systems--different results.
AB  - When a pacemaker is implanted, several electrophysiological parameters are
      measured using pacing system analyzers (PSA). Different PSAs may use different
      filter settings and measuring techniques when compared to the implanted
      pacemaker. In order to determine if there were significant differences in
      measurements obtained with different PSAs, we obtained measurements in a group of
      99 patients with three different PSAs and a manual method. The results show that
      with each of the three different PSAs tested, different amplitudes of
      intracardiac electrograms are obtained and that they are usually higher than
      those obtained by manual measurement of recorded electrograms. Despite
      significant differences, however, all methods correlate well with each other.
      Following common practice of pacemaker programming, the use of a PSA for the
      implantation of a pacemaker that uses different sensing technique does not lead
      to clinical complications.

PMID- 7511230
TI  - Catheter induced mechanical stunning of accessory pathway conduction: useful
      guide to successful transcatheter ablation of accessory pathways.
AB  - Established electrophysiological criteria indicating anatomical proximity to an
      accessory pathway include early ventricular or atrial activation during antegrade
      or retrograde accessory pathway conduction, recording of accessory pathway
      potentials, and pace map concordance. This article describes two cases of RF
      catheter ablation of accessory pathways, during which positioning of the mapping
      catheter at specific sites on the endocardial aspect of the atrioventricular
      annulus led to prolongation of accessory pathway refractoriness and/or slowing of
      conduction. RF energy application at these sites successfully abolished accessory
      pathway conduction. When observed on an "internal" basis during catheter mapping,
      catheter induced stunning of accessory pathway conduction provides evidence of
      satisfactory electrode-tissue contact in addition to anatomical proximity, and
      may give additional predictive value to successful transcatheter accessory
      pathway ablation.

PMID- 7511231
TI  - Conductive property of the zone of slow conduction of reentrant ventricular
      tachycardia and its relation to pacing induced terminability.
AB  - In order to assess the functional characteristics of the zone of slow conduction
      of reentrant VT, rapid pacing was performed to entrain VT. The orthodromic
      conduction time was measured as the interval between the stimulus and the
      orthodromically captured electrogram recorded distal to the zone of slow
      conduction, but not precisely at the exit point, and its response to rapid pacing
      was evaluated. In 32 of 33 consecutive patients, rapid pacing was performed to
      entrain VT. Of these, rapid pacing was repeated in 28 patients at 3-10 cycle
      lengths in steps of 10 msec before VT was terminated, or rapid pacing produced an
      acceleration of the rate. A pacing induced prolongation of the orthodromic
      conduction time (slowed conduction) was observed in 16 (57.1%) patients and in
      another 12 (42.9%) patients, the conduction time was constant. The pacing induced
      termination was observed in 93.8% of VT with slowed conduction and in 50% of VT
      with constant conduction, and the difference was significant (P < 0.05). There
      was no difference in the cycle length of VT or the shortest paced cycle length
      between VT with and without slowed conduction. The zone of slow conduction in
      human VT showed different conductive properties and VT with slowed conduction was
      associated with an easier and safer terminability with rapid pacing. The fact
      might be useful in selecting patients for antitachycardia pacing.

PMID- 7511232
TI  - Long-term performance of endocardial pacing leads.
AB  - To assess the performance of endocardial pacemaker leads and to identify factors
      associated with structural lead failure, medical records of 2,611 endocardial
      pacing leads (in 1,518 patients) implanted between 1980 and 1991, having at least
      1 month of follow-up, were reviewed. Leads without structural failure had normal
      function at the last follow-up date, or were discontinued for reasons other than
      structural failure (patient death, infection, dislodgment, lead-pacemaker
      incompatibility, operative complication, or abandonment by telemetry not related
      to failure). Leads with suspected structural failures were invasively or
      noninvasively disconnected because of clinical malfunction (loss of capture or
      sensing, oversensing, elevated thresholds, or skeletal muscular stimulation).
      Leads with verified structural failures met the criteria for suspected lead
      failure and also had a visible defect seen in the operating room or on chest
      roentgenograms, a change in the impedance interpreted by the physician as lead
      disruption, or a manufacturer's return product report that confirmed structural
      failure. Variables analyzed included patients' age and gender, paced chamber,
      venous access, insulation materials, fixation mechanism, coaxial design,
      polarity, and different lead models. The cumulative lead survival at 5 and 10
      years were 97.4% and 92.9%, respectively, for suspected failures; and 98.7% and
      97.3%, respectively, for verified failures. Leads in older patients (> or = 65
      years old), and leads in atrial position had fewer verified failures (P = 0.014
      and P = 0.007, respectively). Unipolar leads also tended to perform better
      according to the verified definition (P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511233
TI  - Report of the NASPE Policy Conference training requirements for permanent
      pacemaker selection, implantation, and follow-up. North American Society of
      Pacing and Electrophysiology.
AB  - NASPE proposes and supports the concept of a two-tracked training system in
      cardiac pacing. Track I training will properly train physicians for the
      prescription of pacemakers and the monitoring of pacemaker patients, and track II
      training will properly prepare physicians for the implantation of pacemakers.
      Regardless of specialty (cardiologist or surgeon) or training venue (cardiac
      pacing fellowship, cardiac electrophysiology and pacing fellowship, sabbatical or
      mentor sponsored training), it is recommended that these minimum standards be
      required for hospital credentialing. NASPE also supports the voluntary
      institution by training program directors of core pacing training in
      cardiovascular disease and cardiac electrophysiology fellowships. This core
      training does not in itself constitute proper track I or II training for
      physicians interested in adequately prescribing, monitoring, or implanting
      cardiac pacemakers.

PMID- 7511234
TI  - Radiofrequency catheter atrioventricular node ablation in patients with permanent
      cardiac pacing systems.
AB  - Following successful RF ablation of the atrioventricular node (AVN), temporary
      pacing is necessary prior to insertion of a permanent pacemaker. The risks and
      inconvenience of temporary pacing could be avoided if a permanent pacemaker is
      already in place. This study reports the feasibility of RF ablation of the AVN in
      27 patients (age 55 +/- 17 years, 15 males) with hypertrophic cardiomyopathy and
      pacemakers. Indications for AVN ablation were drug refractory atrial fibrillation
      in 24 patients, and rapid AVN conduction preventing septal pre-excitation by DDD
      pacemaker, inserted for relief of left ventricular outflow obstruction, in three
      cases. Sixteen patients had DDD devices and 11 patients had VVI devices. During
      RF ablation, each pacemaker was programmed to VVI at 50 beats/min. The ablation
      catheter was manipulated with fluoroscopic control to avoid close contact with or
      disturbance of the pacing leads. In 16 patients, RF ablation was performed
      immediately following pacemaker implantation but in the remaining patients, the
      AVN was ablated 6-32 months after pacemaker implantation. The power applied was
      25-50 watts for a duration of 15-60 seconds. AV block was achieved in all cases
      but required 34 +/- 36 applications for 16.5 +/- 17.8 min/case. RF ablation
      consistently caused reversion to magnet rate in one patient and temporarily
      inhibited appropriate pacemaker discharge in another. However, no other pacemaker
      or lead malfunction was detected so that temporary pacing was not required in any
      case. At 6 +/- 3 months follow-up, all pacemakers were functioning normally
      without alteration in pacing parameters from baseline.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7511236
TI  - Utility programs for disaster recovery.

PMID- 7511235
TI  - Atrial natriuretic factor: implications for cardiac pacing and electrophysiology.

PMID- 7511237
TI  - Health care reform--the future is now.

PMID- 7511238
TI  - Loss of late potentials after radiofrequency catheter ablation of recurrent
      ventricular tachycardia in a patient with right bundle branch block.
AB  - The case of a patient with a history of myocardial infarction and recurrent
      ventricular tachycardia undergoing attempted radiofrequency catheter ablation
      with loss of late potentials is described. Prior to energy delivery fractionated,
      late activation could be found using the signal-averaged ECG despite the presence
      of a right bundle branch block. After successful catheter ablation, the clinical
      ventricular tachycardia was no longer inducible and the signal-averaged ECG,
      recorded the next day, showed marked changes indicating loss of late potentials.
      Our report emphasizes the possibility of late potential recordings despite the
      presence of bundle branch block.

PMID- 7511239
TI  - Interaction of zidovudine (azidothymidine) with isoprinosine and probenecid in
      Macaca fascicularis.

PMID- 7511240
TI  - Acidic fibroblast growth factor: evaluation of topical formulations in a diabetic
      mouse wound healing model.
AB  - The efficacy of topical formulations of acidic fibroblast growth factor (aFGF) in
      healing of full-thickness wounds has been studied in a diabetic db+/db+ mouse
      model. The effect of several formulation variables, dose, and application
      frequency was examined. It was found that wound healing in diabetic animals
      treated with aFGF or placebo was slower than in their nondiabetic littermates.
      The availability of aFGF from the viscous vehicle employed in this study (1%
      hydroxyethyl cellulose) was demonstrated in vitro using diffusion cells. The
      viscous formulation of aFGF was equally effective in wound healing as a
      nonviscous formulation in phosphate-buffered saline. A formulation containing
      heparin (necessary for full biological and conformational stability of aFGF) at a
      mass ratio of 3:1 to aFGF was more efficacious than formulations with lower
      heparin: aFGF ratios. Wounds treated with three doses of 3.0 micrograms/cm2 aFGF
      healed faster than those treated with a single dose of 3.0 micrograms/cm2 aFGF.
      Three applications of 3.0 or 0.6 microgram/cm2 a FGF were equally effective in
      accelerating wound healing.

PMID- 7511242
TI  - Serum alpha-fetoprotein and neural tube defects in the first trimester of
      pregnancy. MRC Vitamin Study Research Group.
AB  - As part of the Medical Research Council randomized trial of vitamin
      supplementation in the prevention of neural tube defects (NTDs), maternal serum
      alpha-fetoprotein (AFP) was available for 19 NTD pregnancies. Each of these was
      matched with four unaffected controls, by maternal age, participating centre, and
      duration of sample storage. The samples came from women whose gestational age
      ranged from 6 to 14 completed weeks. The median AFP level in the affected
      pregnancies was 1.2 multiples of the median value in unaffected pregnancies of
      the same gestational age (95 per cent confidence interval (CI) 0.83-1.59). This
      confirmed the view that serum AFP measurement is of no practical value in the
      detection of NTDs in the first trimester of pregnancy. The study also showed that
      folic acid supplementation, used as a method of preventing NTDs, had no effect on
      the concentrations of maternal serum AFP up to 14 weeks of pregnancy.

PMID- 7511241
TI  - Diffusion rates and transport pathways of fluorescein isothiocyanate (FITC)
      labeled model compounds through buccal epithelium.
AB  - The aim of this study was to characterize transport of FITC-labeled dextrans of
      different molecular weights as model compounds for peptides and proteins through
      buccal mucosa. The penetration of these dextrans through porcine buccal mucosa (a
      nonkeratinized epithelium, comparable to human buccal mucosa) was investigated by
      measuring transbuccal fluxes and by analyzing the distribution of the fluorescent
      probe in the epithelium, using confocal laser scanning microscopy for visualizing
      permeation pathways. The results revealed that passage of porcine buccal
      epithelium by hydrophilic compounds such as the FITC-dextrans is restricted to
      permeants with a molecular weight lower than 20 kDa. The permeabilities of buccal
      mucosa for the 4- and 10-kDa FITC-dextran (of the order of 10(-8) cm/sec) were
      not significantly different from each other or from the much smaller compound
      FITC. The confocal images of the distribution pattern of FITC-dextrans showed
      that the paracellular route is the major pathway through buccal epithelium.

PMID- 7511243
TI  - [Cancer of the ovary. New therapeutic approaches].

PMID- 7511244
TI  - Epitope analysis of human insulin and intact proinsulin.
AB  - Residues belonging to epitopes on human insulin that were recognized by a panel
      of three monoclonal antibodies were located using mutated insulins and insulins
      from a number of different animal species. Epitopes on human proinsulin
      recognized by two monoclonal antibodies were also identified using partially
      processed proinsulin species. Epitopes were located on the C-A and B-C junctions
      of proinsulin and on the N-termini of the A- and B-chains and the central region
      of the B-chain of human insulin. Antibodies that bound proinsulin were found to
      induce conformational changes in the prohormone. The presence of a well-defined
      interaction between the C-peptide portion and the N-terminus of the A-chain of
      the insulin moiety of intact proinsulin has also been demonstrated. The relevance
      of these studies to the development of two-site assays for the measurement of
      partially processed proinsulin species in human sera is also discussed.

PMID- 7511245
TI  - The BC loop in poliovirus coat protein VP1: an ideal acceptor site for major
      insertions.
AB  - In poliovirus the BC loop of the VP1 coat protein is hypervariable and can
      accommodate numerous foreign sequences introduced by genetic engineering. This
      paper examines the characteristics of the VP1 BC loop of the picornaviruses to
      see why this loop is so variable and particularly favourable for the insertion of
      foreign sequences leading to the formation of chimeric particles. The
      characteristics which make this loop distinctive can be used to find equally
      permissive loops in other proteins.

PMID- 7511246
TI  - Arachidonic acid stimulates interleukin-6 release from rat peritoneal macrophages
      in vitro: evidence for a prostacyclin-dependent mechanism.
AB  - Interleukin-6 (IL-6) is a cytokine involved in the differentiation of B-cells to
      antibody secreting plasma cells, the activation of T-cells, and the stimulation
      of hepatocyte production of acute phase proteins. Because of the pro-inflammatory
      effects of this cytokine, we investigated the ability of the fatty acid
      arachidonic acid (AA) to regulate the release of IL-6 from rat resident
      peritoneal macrophages (M phi) in vitro. AA (0.5-16 microM) stimulated IL-6
      release during a 4 h incubation period in a biphasic manner, with 4 microM AA
      generating a peak of IL-6 release (3-5-fold). AA (0.5-16 microM) also induced an
      increasing release of the AA metabolite thromboxane B2 (TXB2). The AA-induced
      release of IL-6 occurred within 1-2 h of incubation, whereas TXB2 concentrations
      were elevated within 5 min of AA treatment. The TX synthetase inhibitor CGS 12970
      (4.0 microM and 40.0 microM) effectively blocked the generation of TXB2, but
      increased prostacyclin (PGI2) generation and potentiated the release of IL-6. In
      addition, PGI2, as well as the PGI2 agonists iloprost and cicaprost, stimulated
      IL-6 release from M phi by greater than 5-fold over vehicle-treated basal levels.
      These data suggest that PGI2 (but not TXA2) is involved in AA-induced IL-6
      release from peritoneal M phi.

PMID- 7511247
TI  - Relation of dissociative phenomena to levels of cerebrospinal fluid monoamine
      metabolites and beta-endorphin in patients with eating disorders: a pilot study.
AB  - Dissociation is made manifest by a failure to integrate thoughts, feelings,
      memories, and actions into a unified sense of consciousness. Although
      dissociation is presumed to be a special state of consciousness manifested by
      state-dependent memory and physiology, the psychobiology of dissociation is
      poorly understood. In this study, we examined cerebrospinal fluid levels of the
      major monoamine metabolites and beta-endorphin in patients with eating disorders
      (11 with anorexia nervosa, 16 with bulimia nervosa), while they were acutely ill.
      Dissociative capacity was measured using the Dissociative Experiences Scale
      (DES). We provide evidence that neurochemical changes in dopaminergic,
      serotonergic, and opioid systems may be associated with the clinical expression
      of dissociation in patients with eating disorders during the acute phase of their
      illness. These preliminary results are compatible with previous studies of
      neurochemical disturbances in the eating disorders and suggest that future work
      in dissociation should specifically include examination of these neurobiologic
      systems.

PMID- 7511248
TI  - Relationships between interleukin-6 activity, acute phase proteins, and function
      of the hypothalamic-pituitary-adrenal axis in severe depression.
AB  - Recent studies from this laboratory have provided some evidence that major
      depression, in particular melancholia, may be accompanied by an immune response.
      The present study was designed to investigate whether severe depression is
      characterized by increased interleukin-6 (Il-6) activity and whether Il-6
      production is related to altered levels of acute phase reactants and to abnormal
      function of the hypothalamic-pituitary-adrenal (HPA) axis. Measurements were made
      in 8 healthy control subjects and 24 depressed inpatients of Il-6 production in
      culture supernatants of mitogen-stimulated peripheral leukocytes and plasma
      levels of haptoglobin (Hp), transferrin (Tf), and postdexamethasone cortisol. Il
      6 activity was significantly higher in melancholic subjects than in healthy
      control subjects and in patients with minor depression or nonmelancholic major
      depression. Il-6 production was significantly correlated with Hp (positively) and
      Tf (negatively) plasma levels. There were significant and positive correlations
      between Il-6 activity and postdexamethasone cortisol values. The findings may
      suggest that increased Il-6 activity in severe depression is related to
      hypotransferrinemia, hyperhaptoglobinemia, and hyperactivity of the HPA axis.

PMID- 7511249
TI  - Atrial natriuretic factor enhances induced salivary secretion in the rat.
AB  - As atrial natriuretic factor (ANF) is intimately involved in water and
      electrolyte homeostasis, dose-response studies were performed in the parotid as
      well as submaxillary glands of the rat with increasing doses of the atrial
      peptide to investigate its possible role as a sialogogic agent. Dose-response
      studies were also performed in both salivary glands with different
      pharmacological agonists known to cause salivation in the rat (methacholine,
      noradrenaline, isoproterenol, methoxamine and substance P) in the absence and in
      the presence of ANF. The atrial factor did not induce salivation 'per se' at
      least in the investigated doses. However, it enhanced the salivary response to
      methacholine, methoxamine and substance P but it did not modify the salivation
      induced either by noradrenaline or isoproterenol. The present results showed that
      ANF enhanced the salivation induced by pharmacological agents which stimulate
      phosphatidylinositol hydrolysis. These effects of ANF may be probably related to
      the activation of the non-guanylate cyclase coupled receptor which has been
      associated with phosphatidylinositol turnover. Nevertheless, although the atrial
      factor induces vasorelaxation, its enhancement of blood flow may not be the major
      event underlying the present results. The present work suggests a potential
      physiological role of ANF on the modulation of salivary secretion and provides
      further evidence on the rol of ANF in the regulation of body fluid homeostasis.

PMID- 7511250
TI  - Tumor angiogenesis: review of current applications in tumor prognostication.
AB  - The first requirement of a new prognostic indicator is that it should possess a
      clear biological significance. Indeed, much evidence shows that tumor growth and
      metastasis depend on neovascularization. Tumor angiogenesis (TA) refers to the
      growth of new vessels toward and within the tumor; unless tumor
      neovascularization occurs, cell proliferation reaches a steady state, and the
      tumor grows no larger than about 2 mm greatest diameter. Moreover, for tumor
      cells to metastasize, they must gain access to the vasculature from the primary
      tumor, survive the circulation, localize in the target organ, and induce
      angiogenesis in that target organ. TA is necessary both at the beginning and at
      the end of the metastatic cascade of events. Recently, my colleagues and I showed
      that a statistically significant correlation exists between incidence of
      metastases and microvessel density (MVD) of primary invasive breast carcinomas.
      Now, subsequent studies have shown that the association of prognosis with MVD
      exists not only in breast carcinoma but also in non-small-cell lung carcinoma,
      prostate carcinoma, and head-and-neck carcinoma. This article reviews the
      concepts and mechanisms of TA, the evidence supporting its role in growth and
      metastasis of solid tumors, and how measuring MVD within invasive tumors
      correlates with factor VIII-related antigen, blood vessel.

PMID- 7511251
TI  - The effect of different preparations of nasal decongestants on ciliary beat
      frequency in vitro.
AB  - Ciliated cells from the nasal mucosa of normal persons were collected in culture
      medium and exposed to either oxymetazoline without preservatives, oxymetazoline
      with preservatives, xylometazoline with preservatives, or sham (culture medium).
      There was a significant decrease in ciliary beat frequency only by the two drugs
      with preservatives after 20 min. After substitution of the test media with
      culture medium ciliary action did not recover in any group.

PMID- 7511252
TI  - Antigen-specific human T-cell colony formation in a liquid culture system.
AB  - We have developed a limiting dilution microculture T-cell cloning technique to
      generate antigen-specific T-cell clones. Cultures contained peripheral blood T
      cells, irradiated autologous mononuclear cells (feeders), human AB serum and
      recombinant IL-2. Colonies were enumerated at 14 days. Under these conditions the
      cloning efficiency expressed as the frequency of proliferating cells in response
      to PHA, ranged from 1/1.07 to 1/3.35. In response to tetanus toxoid, the
      frequency of proliferating cells ranged from 1/415 to 1/5655. Average colony size
      ranged from 0.7 x 10(5) to 6.2 x 10(5) cells with a mean T-cell recovery of 2.5 x
      10(5) cells per microculture. Restimulation of 14-day tetanus toxoid T-cell
      colonies revealed marked proliferation to PHA and tetanus toxoid but only
      background responses to PPD. These studies document the development of a rapid,
      antigen-specific liquid culture T-cell cloning system which is likely to detect T
      cell clones that are representative of the original T-cell population. The clones
      are of sufficient size to be useful in studies of antigen cross-reactivity.

PMID- 7511254
TI  - Macromolecular selectivity of chick chorioallantoic membrane microvessels during
      normal angiogenesis and endothelial differentiation.
AB  - Progressive angiogenesis and endothelial differentiation in the chick
      chorioallantoic membrane (CAM) serve to accommodate oxygen demands of the growing
      embryo. The present study evaluated CAM microvascular endothelial permselectivity
      during the most rapid phase of angiogenesis (day 10) and after initiation of
      endothelial cytodifferentiation (day 14). Chick embryos were incubated using
      established shell-less culture techniques for intravital and ultrastructural
      observations. Systemic microinjections of FITC-dextrans (40, 70 and 150 KDa)
      provided an index of endothelial permselectivity after 2.5 min and 10 min
      perfusions. Ultrastructural examinations of the same dextran probes served to
      detect small, intermittent foci within the perivascular interstitium. Although
      minor variations of dextran particle distributions around specific segments of
      the microcirculation were observed ultrastructurally, perivascular accumulation
      was not sufficient to elicit a detectable fluorescent signal. Thus, substantial
      accumulation of the graded-dextran series in the perivascular interstitium was
      not detected. Morphometric analyses of the precapillary, capillary, and
      postcapillary microvascular segments served to demonstrate a continuous
      endothelium which displayed cytoplasmic attenuation at day 14. Plasmalemmal
      vesicles were few and uniform within the microvascular units at day 10. A three
      fold increase in vesicle densities characterized the precapillary endothelia at
      day 14. Average widths of the endothelial junctional clefts were homogeneous
      within the segmental microvascular endothelia at both days 10 and 14. Junctional
      cleft lengths were also homogeneous, except the significantly longer capillary
      endothelial clefts observed at day 10. These results are consistent with the
      concept that, despite certain differences in segmental vesicle densities and
      junctional cleft lengths, neovascularization of the CAM is achieved without
      excessive macromolecular efflux across the microvascular endothelia.

PMID- 7511253
TI  - Crystal structure of the principal neutralization site of HIV-1.
AB  - The crystal structure of a complex between a 24-amino acid peptide from the third
      variable (V3) loop of human immunodeficiency virus-type 1 (HIV-1) gp 120 and the
      Fab fragment of a broadly neutralizing antibody (59.1) was determined to 3
      angstrom resolution. The tip of the V3 loop containing the Gly-Pro-Gly-Arg-Ala
      Phe sequence adopts a double-turn conformation, which may be the basis of its
      conservation in many HIV-1 isolates. A complete map of the HIV-1 principal
      neutralizing determinant was constructed by stitching together structures of V3
      loop peptides bound to 59.1 and to an isolate-specific (MN) neutralizing antibody
      (50.1). Structural conservation of the overlapping epitopes suggests that this
      biologically relevant conformation could be of use in the design of synthetic
      vaccines and drugs to inhibit HIV-1 entry and virus-related cellular fusion.

PMID- 7511255
TI  - The effect of administration of FK506 on delayed regeneration in flushed
      partially hepatectomized livers.
AB  - It has been shown previously that liver regeneration after partial hepatectomy in
      rats is delayed if the liver is subjected to either concurrent ischaemia,
      flushing with cold solution, or grafting. We have shown recently that treatment
      with CsA preoperatively overcomes the suppressive effect of flushing and returns
      the regenerative response to a normal time scale. The present study was designed
      to investigate whether administration of FK506 would also return the observed
      delayed regenerative response to normal. Long-Evans rats weighing 250-350 g were
      subjected to standard 68% partial hepatectomy. Group 1 had no further treatment;
      in group 2, the liver remnant was flushed with 10 ml cold (4 degrees C) Ringers
      lactate solution, and in group 3, FK506 (1 mg/kg/day) was administered by
      intramuscular injection for 3 days before the partial hepatectomy and flushing as
      in group 2; a final dose was given after completion of the procedures. Animals
      were killed in sets of 6 per group at 4, 24, 48, 72, and 96 hr after surgery and
      blood samples were taken for measurement of plasma aspartate amino-transferase.
      Liver biopsies were analyzed for measurement of thymidine kinase and ornithine
      decarboxylase activity and for counting of mitotic figures. While the highest
      recorded thymidine kinase activity occurred in group 1 at 24 hr, this was delayed
      to 48 hr in both group 2 and 3 and counts remained high up to 96 hr in group 3.
      Mitotic indices were only significantly elevated (compared with group 1 at 96
      hr), while ornithine decarboxylase activity did not correlate with these changes
      being significantly lower than in groups 2 and 3 at 4 hr and in group 3 also at
      24 hr. Plasma aspartate aminotransferase was also significantly higher in group
      3. It is concluded that the administration of FK506 preoperatively to rats
      subjected to partial hepatectomy and flushing did not restore the delayed
      regenerative response to normal but enhanced the response (as measured by
      thymidine kinase but not by mitotic indices) which commenced at 48 hr and was
      still present at 96 hr.

PMID- 7511256
TI  - Treatment of mice with anti-CD3 mAb induces endothelial vascular cell adhesion
      molecule-1 expression.
AB  - In vivo treatment of mice with anti-CD3 mAb causes polyclonal T cell activation
      and cytokine release. Since several cytokines are known to alter expression of
      MHC molecules and adhesion molecules on endothelia, we hypothesized that anti-CD3
      mAb treatment should result in activation of vascular endothelia. In previous
      studies, we established that vascular endothelial cells in murine heterotopic
      cardiac grafts can develop at least 2 stable inflammatory phenotypes: cardiac
      allograft endothelia characteristically develop reactivity with MECA-32 mAb
      (undefined endothelial epitope) and M/K-2 mAb (murine vascular cell adhesion
      molecule-1 [VCAM-1]), whereas cardiac isografts develop reactivity with MECA-32,
      but not M/K-2 mAb. We now report that a single treatment of cardiac isograft
      recipients with the anti-CD3 mAb 145-2C11 caused expression of VCAM-1 on all
      cardiac isograft endothelia, including the microvascular endothelia. In contrast,
      expression of endothelial VCAM-1 in the native heart of the isograft recipient
      was limited to patchy areas of larger arteries. This patchy, arterial pattern of
      VCAM-1 expression was observed in lung, liver, kidney, and thymus of all mice
      treated with 145-2C11, whether or not they were implanted with a cardiac
      isograft, and was dissociated from expression of MECA-32 mAb reactivity. Hence,
      treatment of mice with anti-CD3 mAb causes systemic endothelial activation (VCAM
      1 expression), and endothelial cells of recently implanted cardiac isografts
      appear to be hypersensitive to induction of VCAM-1 by anti-CD3 mAb treatment.
      Further studies showed that (1) treatment with 145-2C11 F(ab)'2 fragments did not
      induce endothelial activation, (2) intravenous pretreatment with pentoxifylline
      eliminated all endothelial effects of 145-2C11 treatment, (3) induction of
      endothelial activation by 145-2C11 mAb always paralleled the expression of
      adverse physiologic symptoms, and (4) mice exhibit strain-specific differences in
      endothelial responses to 145-2C11 treatment. We propose that anti-CD3 mAb
      treatment causes simultaneous activation of circulating T cells and systemic
      vascular endothelial cells which may facilitate systemic lymphocyte-endothelial
      interactions, and may explain the rapid disappearance of T cells from the
      circulation that is associated with anti-CD3 treatment in mouse and man.

PMID- 7511257
TI  - Immunocytochemical study of pancreatic islet revascularization in islet isograft.
      Effect of hyperglycemia of the recipient and of in vitro culture of islets.
AB  - We studied the revascularization process of isogeneic islets grafted into the
      kidney subcapsular space of streptozotocin-induced diabetic and nondiabetic rats
      by a double-labeling, indirect immunofluorescence technique using a rabbit
      antiserum to human factor VIII-related antigen (which identifies endothelial
      cells) and a guinea pig anti-insulin antiserum (which labels pancreatic beta
      cells). Freshly isolated islets contained a network of capillary endothelial
      cells, whereas 1-week-cultured islets at 37 degrees C have completely lost their
      intra-islet endothelial cells. Overnight cultured islets contained only
      occasional endothelial cells. When these islets were grafted under the kidney
      capsule of nondiabetic rats, they rapidly acquired a new endothelial cell lining
      as demonstrated by the positivity of staining for factor VIII-related antigen at
      day 5 after implantation. On the other hand, 1-week-cultured islets failed to
      become fully revascularized until day 7 after transplantation. Streptozotocin
      induced diabetic rats grafted with 1000 islets normalized their blood glucose
      values (< 11 mM/L) 2-4 weeks after implantation, whereas transplantation of 2500
      3000 islets resulted in normoglycemia after 4.7 +/- 2 days (mean +/- SD).
      Nevertheless, hyperglycemia of the recipient did not adversely affect the process
      of revascularization of islet isografts which initiated at day 3 and was almost
      completed by day 5 after implantation.

PMID- 7511260
TI  - Is there a change in the treatment of benign prostatic hyperplasia?

PMID- 7511259
TI  - Influence of anti-hepatitis C virus antibody on kidney transplant survival in a
      single Japanese center.

PMID- 7511258
TI  - Anti-CD2 monoclonal antibodies synergize with FK506 but not with cyclosporine or
      rapamycin to induce tolerance.
AB  - CsA, FK506, and rapamycin prolong allograft survival; however, each has
      significant associated side effects at therapeutic doses. Anti-CD2 mAbs also
      prolong survival but without toxicity. We tested whether alpha CD2 mAbs in
      combination with subtherapeutic immunosuppression could prolong allograft
      survival in a synergistic fashion. C57BL/6 (H-2b) mouse hearts were transplanted
      to CBA (H-2k) mice in a heterotopic, non-vascularized cardiac allograft model.
      Recipients received immunosuppressants intraperitoneally for 14 days and/or alpha
      CD2 mAb intravenously for 2 days starting at the time of grafting. Survival was
      determined by electrocardiogram monitoring. Anti-CD2 alone prolonged survival to
      22.4 +/- 1.0 days versus 13.4 +/- 0.5 days for untreated controls (P < 0.05),
      while low dose FK506 minimally prolonged survival to 16.7 +/- 0.7 days (P <
      0.057). However, FK506 plus alpha CD2 resulted in synergistic prolongation of
      graft survival to 28.0 +/- 2.1 days. Several doses of CsA and rapamycin in
      combination with alpha CD2 did not prolong survival over alpha CD2 administered
      alone. A 60-day course of low dose FK506 plus alpha CD2 resulted in indefinite
      graft survival (> 165 days). These animals were tolerant since they accepted a
      second donor-specific graft. CTL and MLR activity in long-term recipients were
      normal to both donor-specific and third party alloantigen. The combination of
      alpha CD2 with low dose FK506 is synergistic in prolonging cardiac allograft
      survival, while combinations with CsA and rapamycin are not. Continuous
      administration of low dose FK506 plus alpha CD2 results in a state of tolerance.
      This suggests that FK506 acts at a different locus in allograft immunity compared
      with the other immunosuppressants and this may be related to the alternative CD2
      T cell activation pathway.

PMID- 7511261
TI  - [Mechanisms of the antitumor effects interferons].
AB  - Interferons alpha, beta and gamma form an interferon system, which is part of the
      non-specific immune defense of the organism. They participate in the defense
      against virus infections and have a marked immunoregulating effect. By
      interfering with the transmission of genetic information in the cells they exert
      an antiproliferative action on sound as well as tumour cells (they inhibit
      oncogenes). Alpha interferon exerts the most marked antiproliferative action. All
      mentioned mechanisms participate in the anti-tumourous action of interferons. The
      most widely used interferon in oncological treatment is interferon alpha.

PMID- 7511263
TI  - [Current Views on Prostate and Urinary Tract Pathology. Proceedings of the 24th
      fall meeting. 8-10 October 1993].

PMID- 7511265
TI  - [Immunohistochemical and morphometric studies on neuroendocrine differentiation
      of prostate carcinomas].
AB  - 102 unselected and untreated prostate carcinomas were immunohistochemically
      analysed with regard to neuroendocrine (ne) differentiation using a monoclonal
      antibody against Chromogranin A. Density of ne-tumor cells/mm2 tumor area and
      arrangement of ne-tumor cells (single cells; small groups and large groups) were
      determined. We found ne-tumor cells in 90% of all carcinomas (n = 92). 70% had a
      low density of ne-tumor cells (< or = 1 cell/mm2). 67% of carcinomas with ne
      differentiation showed only single ne-tumor cells, there were small groups in 19%
      and large groups in 14%. There was an association between higher densities of ne
      tumor cells and arrangement in groups. In high malignancy carcinomas we found a
      higher density of ne-tumor cells and more often an arrangement in groups than in
      low grade tumors. Our results support reports in literature that ne
      differentiation is of prognostic significance.

PMID- 7511264
TI  - [In vivo and ex vivo expression of nucleolar proliferation-associated antigens
      (p120, B23) in the prostate].
AB  - Expression of two nucleolar antigens, p120 and B23, was studied in a prostatic
      carcinoma cell line (LNCaP) and in frozen and paraffin embedded tissue sections
      of 40 benign and malignant prostatic lesions. The percentage of p120 negative
      G0/G1 phase cells rose significantly during transition from exponential to
      plateau growth phase in vitro (from 9% to 32%). In contrast, B23 was equally
      expressed throughout different cell cycle and growth phases. Thus, nucleoli of
      almost all stromal and epithelial cells were stained by B23 in tissue sections.
      P120, however, selectively stained nucleoli of proliferating prostatic
      epithelium. Whereas 88% (13/15) of benign hyperplasia were p120 negative this was
      the case in only 24% (6/25) of carcinomas. Using microwave procedure both MoAbs
      reacted in paraffin sections, but the percentage of p120 negative cases doubled.
      A routine application to formalin fixed and paraffin embedded tissue cannot be
      recommended thus far.

PMID- 7511262
TI  - [Current aspects on morphology and functions of the prostate].
AB  - The human prostate has a dual function in that it produces a number of secretory
      compounds conditioning the urethral surface for sperm passage and acting on
      spermatozoa as well as on vesicular coagulation proteins (semen liquefaction). In
      addition to differentially distributed and regulated steroid hormone receptors in
      epithelium and stroma, the prostate contains a large number of growth factors and
      their receptors. An incompletely understood paracrine regulation of growth and
      differentiation exists between epithelial cells, such as secretory, basal and
      neuroendocrine cells, as well as the underlying stroma (smooth muscle cells,
      fibrocytes). The presently available (malignant and non-malignant) prostatic cell
      lines have a number of disadvantages that render them of limited value in
      prostate cancer research.

PMID- 7511266
TI  - [Morphological classification and comparison of the different types of stromal
      nodules in benign prostatic hyperplasia].
AB  - The expression of immunohistochemical markers for cytoskeletal differentiation
      and that of neuroendocrine- and immunological cells showed in general the same
      tendency in the 4 types of prostatic stromal nodules: missing or low expression
      in immature-mesenchymal-, distinct augmentation in fibroblastic-, a maximum in
      fibro-muscular- and a slight decline in smooth-muscular nodules. These results
      are in agreement with developmental sequences, revealed by immunohistochemical
      investigations of fetal prostates, and seem to confirm the hypothesis that the
      four types of stromal nodules represent successive degrees of maturation,
      recapitulating ontogenetic processes.

PMID- 7511267
TI  - [p53 in urogenital tumors:analysis of expression and mutation].
AB  - DNA and paraffin material of more than 100 tumors of prostate, bladder and female
      genital organs were analyzed for p53 aberrations and compared with normal tissues
      by immunohistochemistry, PCR of p53 exons 5-8 and TGGE. While normal tissues,
      precancerous and borderline lesions, and well differentiated carcinomas usually
      showed wild type p53 and negative immunostaining, high grade and/or high stage
      carcinomas often revealed mutant p53 (rate of mutation in exon 8 >> 7 >> 6 >> 5)
      and/or p53 accumulation. Accumulation of p53 protein in the absence of detectable
      mutant p53 was recognized more often in prostate cancer than in any other tumor
      examined. Although p53 aberration probably represents a late molecular event in
      cancerogenesis, its detection may be of clinical interest as genetic footprint in
      recurrent and metastatic disease.

PMID- 7511268
TI  - [Androgen receptor gene mutations and p53 gene analysis in advanced prostate
      cancer].
AB  - One of the most interesting but still unsolved issues in prostate cancer is the
      role of androgens, the androgen receptor (AR) and the p53 tumor suppressor gene
      in the development and/or progression of prostatic neoplasia. DNA obtained from
      prostate tissues of 7 normal donors, 5 BPH and 10 adenocarcinomas at different
      stages was amplified by the polymerase-chain-reaction (PCR). The products were
      analysed by single strand conformation polymorphism (SSCP), and by direct
      sequencing of those that displayed altered electrophoretic behavior. The
      molecular analysis of exons 1 to 8 of the AR gene revealed point mutations in
      codons 340 (exon 1) and 798 (exon 6) in 2/10 prostate carcinomas. No mutations
      were found in the p53 gene. Our findings suggest that mutations of the AR gene
      are relatively frequent in prostate cancer and may have therapeutical
      significance.

PMID- 7511269
TI  - [Androgen regulation of secreted growth factors in prostate carcinoma cell and
      tumor lines].
AB  - Previous studies have shown that part of steroid hormone action on hormone
      dependent carcinoma cells is mediated through secreted autocrine and paracrine
      growth factors. Coculture experiments using the androgen receptor positive human
      prostate carcinoma cell line LNCaP as feeder cells and the androgen receptor
      negative prostate cell line DU 145 as indicator cells, such as experiments with
      conditioned medium suggest that androgens might regulate proliferation of
      prostate carcinoma through a similar mechanism. LNCaP and DU 145 cells express
      high affinity EGF-receptors and show an increased growth rate under treatment
      with EGF, TGF alpha and FGF. The growth stimulating potential of LNCaP
      conditioned medium can be enhanced by androgens. The polyanionic compounds
      suramin and dextran sulfates which have been shown to inactivate a variety of
      growth factors e.g. EGF/TGF alpha inhibit growth of LNCaP cells and DU 145 cells
      in a dose dependent and reversible fashion. Growth stimulation of LNCaP cells by
      EGF/TGF alpha can be completely reversed by simultaneous addition of polyanions
      but they inhibit androgen stimulation only partially. These data suggest the
      existence of at least two different mechanisms of growth regulation by androgens
      which can be distinguished by their different sensitivity of prostatic carcinoma
      cells to growth factor inhibitory agents. In order to investigate the therapeutic
      potential of these substances in complex, heterogeneous cell systems of solid
      tumors we treated 8 representative human prostate cancer lines in the nude mouse
      model. Systemic applications of polyanions revealed significant growth inhibition
      in hormone dependent as well as hormone independent xenografts. In androgen
      responsive lines growth inhibition was intensified by additional androgen
      withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511270
TI  - [Differential regulation of androgen receptor promoter in hormone-sensitive and 
      insensitive prostate carcinoma cells].
AB  - The sensitivity of prostate epithelial cells to androgens is mediated by the
      androgen receptor (AR). Analyses of cell lines in vitro and prostate carcinomas
      in vivo provide evidence that loss of AR expression parallels the loss of
      sensitivity to androgens. The aim of our work is to analyze the genetic control
      elements of the AR gene and answer the question of why these elements fail to
      function in hormone-insensitive prostate cancer cells. Therefore, we have cloned
      and fully sequenced a 5700 base pair sequence 5'-upstream of the AR gene. This
      DNA fragment contains promoter and enhancer elements that are active in androgen
      sensitive but inactive in androgen-insensitive prostate cancer cell lines.

PMID- 7511271
TI  - [Significance of numerical chromosome aberrations in prostate cancer].
AB  - Thirty-one routinely processed radical prostatectomy specimens were examined for
      the presence of numerical chromosomal aberrations by in situ hybridization with
      centromeric nucleic acid probes specific for chromosomes 7, 10, 17, X, and Y. In
      eight of the prostatectomy specimens, chromosome numbers consistent with a normal
      male karyotype were found. Three cases, in addition to diploid chromosome
      numbers, showed a focal doubling of hybridization signals, consistent with
      tetraploidy. The other 20 cases displayed more or less marked numerical
      chromosomal aberrations. In this group, the appearance of numerical chromosomal
      aberrations often showed considerable local heterogeneity and was significantly
      correlated with tumor stage, Gleason grades, and tumor volume. We conclude that
      in prostatic cancer the presence of numerical chromosomal aberrations is
      associated with advanced disease. Especially in low differentiated tumors local
      heterogeneity in chromosome numbers can be very marked.

PMID- 7511272
TI  - [Cytogenetic investigations in primary prostate carcinomas].
AB  - Primary cultures of 48 cases of prostate carcinoma were established. The
      expression of cytokeratin and prostate specific antigen were determined in the
      cultures routinely. G-banding analysis revealed some clonal numerical and
      structural aberrations: Trisomy 7 occurred in 4 cases, in one case in combination
      with a t(Y;22). Loss of the Y chromosome was found in 3 cases, in one case in
      combination with gain of chromosome #5. The most frequent clonal structural
      aberration var9(qh) occurred in 6 cases. A deletion of 6q(23) was found in two
      cases. None of these aberrations were found in normal tissue of the same
      patients. Numerical changes were demonstrated by fluorescence in situ
      hybridization (FISH) on native tissue, confirming the conventional cytogenetic
      findings.

PMID- 7511273
TI  - [Incidence and morphology of coexisting carcinomas of the urinary bladder and
      prostate].
AB  - The objective of the present study was to determine the incidence of coexisting
      carcinomas of the urinary bladder and prostate using biopsy material obtained by
      transurethral resection and to identify the histologic tumor types including
      grading and staging. The incidence of double carcinomas was found to be 4.2%
      referring to all bladder carcinomas studied (n = 1228) and 17.7%, respectively,
      considering only those cases for which biopsies were available from both organs
      (n = 294). The overwhelming majority (81%) of the bladder carcinomas represented
      well and moderately differentiated papillary transitional cell carcinomas (grades
      1 and 2) showing a low staging. Accordingly, most of the prostatic carcinomas
      (78.6) were well and moderately differentiated uniform glandular and pluriform
      glandular-cribriform types of a low staging.

PMID- 7511275
TI  - In vitro studies on the pathogenesis of bladder cancer.
AB  - Three methods for the culture of human urothelial cells in vitro are described:
      (1) the propagation of primary cultures and cell lines derived from normal
      urothelial cells, (2) the immortalization of normal urothelial cell lines with a
      temperature-sensitive SV40 large T antigen and (3) continuous cell lines derived
      from bladder cancers. Such cultures provide model systems for studying the
      factors that control the growth and differentiation of both normal and neoplastic
      urothelial cells, and for defining the morphological, biochemical and genetic
      changes associated with the development and progression of bladder cancer.

PMID- 7511274
TI  - [Etiology, pathogenesis and epidemiology or urothelial tumors].
AB  - A hospital-based case-control study of 531 male and 144 female matched pairs was
      conducted to analyse the role of nonoccupational and occupational risk factors in
      the etiology of tumors of the lower urinary tract. Smoking of cigarettes was
      associated with an increased risk and showed a significant dose- and time
      response for both sexes. Heavy pipe smoking also significantly increased the
      risk. Controlling for smoking, a significantly twofold or more increase in risk
      was found for heavy consumption of coffee in both sexes and for heavy intake of
      beer in males. Increasing levels of total fluid intake were associated with
      increasing, smoking-adjusted risks in men. Significant associations were found
      for chronic infection of the lower urinary tract, familial history of bladder
      cancer, and frequent consumption of high fat meals among men and for frequent
      consumption of canned food in both sexes. With regard to occupational history,
      significantly elevated risks were found for ever-employment in the printing,
      plastics and synthetics, rubber, mining and dyestuffs industries, for exposure to
      spray paints, zinc, chromium/chromate, oils, petroleum and metal dust/fume, and
      for occupation as mining worker and truck driver among men. Multivariate logistic
      regression analysis showed-with the exception of fluid intake-significant
      contribution of the above-mentioned risks factors to the risk of bladder cancer.

PMID- 7511276
TI  - [Prognostic relevance of cytometric methods for tumors of the urinary tract and
      prostate].
AB  - Cytometry means quantification of various cellular parameter using different
      instruments like computer based image analysers, flow cytometers or laser-scan
      microscopes. Using the more time consuming computer based image analysis,
      different parameters of possible prognostic validity for tumors of the urothelium
      or prostate may be quantified, like cellular structures, DNA-ploidy, chromosomal
      aberrations (interphase cytogenetics) AgNORs and a variety of functional antigens
      like proliferation markers, hormone receptors or oncogene products. The advantage
      of this method is that measurements can be performed on selected, morphologically
      classified cells. Using flow cytometers a representative number of tumor cells
      can be measured in a short time. With laser-scan microscopes oncogene
      amplification and chromosomal aberrations may be measured using fluorescence DNA
      in situ-hybridization. Of all cytometric parameters obtainable at present, only
      DNA ploidy is of clinical relevance in transitional cell carcinomas as it can
      predict the probability of tumor recurrence, -progression and of survival time
      with high accuracy. Similarly, at this time, only DNA measurements are of
      clinical relevance in prostatic cancer, as they can predict tumor progression,
      death from cancer, survival probability and sensitivity to hormonal treatment. No
      other grading parameter is of comparable prognostic significance in prostate
      cancer.

PMID- 7511277
TI  - [Tumor-like and preneoplastic lesions as well as low risk and high risk
      urothelial tumors].
AB  - In its first part the review deals with all known hyperplastic, metaplastic as
      well as dysplastic urothelial changes and discusses their possible preneoplastic
      nature. The various changes are classified as indirect, facultative and
      obligatory premalignant lesions. In its second part, the review considers the
      tumor-like growths. In particular, it focuses on the pseudotumorous effects of
      various urocystitis types, postoperative spindle cell pseudosarcoma, glandular
      and nephrogenic metaplasias, malakoplakia and some tissue heterotopias and
      malformations. In its last part, the review critically compares the
      classification principle of the urothelial neoplasias into low-risk and high-risk
      tumors with other tumor classifications (superficial carcinoma/low-grade and high
      grade tumors). The significance of recent study results for assessing the risk of
      urothelial carcinomas is discussed.

PMID- 7511278
TI  - [Non-urothelial tumors of the urinary tract].
AB  - Only about 2% of the urinary tract are not of urothelial origin. Our knowledge of
      their morphology and biology is mainly based on single case reports, and
      therefore apart from a few exceptions very poor. Generally, the most often
      affected site is the urinary bladder (79.2%), followed by the urethra (12.7%),
      pelvis (4.9%) and ureter (3.2%). The urinary bladder also is the only organ in
      which all different histological types of these tumors were described. According
      to their histogenesis non-urothelial tumors (NUT) can be classified by the
      following main groups: soft tissue tumors, mixed epithelial and non epithelial
      tumors (carcinosarcomas), neuroendocrine carcinomas, carcinoids, malignant
      lymphomas, malignant melanomas and extragonadal germ cell tumors. Moreover some
      very interesting tumor-like lesions, like malakoplakia and inflammatory
      pseudosarcoma, mainly occur in this region. About 75% of all NUT of the urinary
      tract belong to the soft tissue tumors. Rhabdomyosarcomas in children and
      leiomyomas and -myosarcomas in adults are the more frequent histological types.
      Leiomyosarcomas can easily be confused with other tumor types or even with
      inflammatory pseudotumors. The use of immunohistochemistry to achieve a correct
      diagnosis is mandatory but not always successful. A relatively frequent tumor
      occurring in the bladder of young adults is the paraganglioma (pheochromocytoma),
      which usually produces typical symptoms of catecholamine excess. Carcinosarcomas
      of the urinary bladder contain both epithelial and mesenchymal components. They
      have to be distinguished from collision tumors (coexistent but separate carcinoma
      and sarcoma), spindle cell transitional carcinomas as well as from carcinomas
      with osseous or cartilaginous metaplasia. Carcinoids and neuroendocrine
      carcinomas developed from the neuroendocrine cells scattered all over the
      transitional epithelium of the bladder. Neuroendocrine carcinomas of the bladder
      are also called "oat cell carcinomas" since they show the same histological
      features and immunoreactivity as the oat cell carcinomas of the lung. They share
      also the same poor prognosis. The affection of the urinary tract in generalized
      malignant lymphomas and leukemias occur in more than 30% of cases. Lymphomas,
      primarily localised in the urinary bladder are, however, extremely rare. The most
      frequent ones are low grade non Hodgkin lymphomas, although 3 cases of Hodgkin
      disease and a few cases of primary extramedullary plasmacytoma of the bladder
      have been reported, too.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7511280
TI  - [Therapeutic strategies in patients with bladder tumors according to
      histopathological findings].
AB  - The therapeutic strategy in patients with bladder carcinoma depends on general
      conditions, i.e. age of the patient, history, i.e. primary tumor versus recurrent
      tumor and on the histopathological finding according to the transurethral
      resection. Exophytic tumor, tumor burden as well as deep muscle layer have to be
      investigated combined with urinary cytology. Independent prognostic factors are
      depth of infiltration, differentiation grade, concomitant carcinoma in situ
      (TIS), lymph node metastases or distant metastases. Carcinoma in situ is
      characterized by an intraepithelial growth, poorly differentiated tumor cells and
      an completely disturbed growth pattern (Fig. 1). Those histopathological findings
      are of great importance for further therapy. Patients with poorly differentiated
      superficial bladder carcinoma or patients with carcinoma in situ are treated by
      adjuvant chemo- or immunotherapy. Radical cystectomy is indicated in all cases of
      recurrent T1 G3 carcinoma or persistent carcinoma in situ. The histopathological
      investigation of regional lymph nodes is of great prognostic value and influences
      the therapeutic strategy. Patients with positive lymph nodes (N2-N3) should not
      be considered for radical cystectomy because these patients will have no survival
      benefit. Histopathological examination of distant metastases are without
      prognostic or therapeutic value because these patients are normally treated by
      systemic chemotherapy.

PMID- 7511279
TI  - [Androgen and estrogen metabolism in human benign prostatic hyperplasia (BPH)].
AB  - Among all androgen metabolizing enzymes within the human prostate 5 alpha
      reductase is the most powerful one. In the epithelium its activity decreases with
      age, while in the stroma it remains constant over the whole age range. Thus, in
      older prostates with benign hyperplasia the activity of 5 alpha-reductase is
      almost the same in both compartments. The same holds true for the DHT content,
      being highest in the epithelium of prostates from young men. With age it
      decreases to levels similar to those in the stroma. In contrast to DHT, estrogens
      are increasingly accumulated in the stroma with advancing age, while in the
      epithelium the estrogen level remains constant over the whole age range. The age
      dependent decrease of the DHT level in the epithelium and the increase of the
      estrogen level in the stroma lead to a significant increase of the
      estrogen/androgen ratio. This could be of pathobiological importance for BPH
      development.

PMID- 7511281
TI  - [Multiparameter analysis using flow cytometry as additional tool for bladder
      cancer diagnosis].
AB  - In order to find additional ways to classify bladder cancer, multiparameter
      analysis with antibodies against urothelial associated-glycoproteins (UAGAb:
      Uro1, -5, -9, -10; Signet) and cytokeratins (CKAb: KL1, Immunotech) were used in
      parallel with DNA staining. Single cell suspensions of 21 bladder cancer
      specimens (4pTaG1, 9pTaG2, 1pT1G2, 2 > pT2G2, 5 > pT2G3) were stained.
      Preliminary data showed that the proportion of UAGAb positive cells have to be
      related to the pan-urothelial marker Uro5, since percentage of urothelial cells
      was variable (30-97%). Phenotypic differences found in different stages of tumor
      will be described. Selection of tumor cells by UAG did result in higher precision
      to determine tumor S-phase fraction, and helped select tetraploid tumors. The
      methodology is best applicable to pTa and pT1-tumors and prospective analysis of
      these tumors has started.

PMID- 7511282
TI  - [Urinary bladder nuclear cytology: results of karyometric investigations].
AB  - To assess the value of nuclear morphometry in the cytological diagnosis of
      urinary bladder carcinoma, washouts of the urinary bladder from 168 patients with
      histological established bladder cancer were studied. Morphometrical measurements
      were done on the nuclei of the exfoliated cells. This retrospective study showed
      that the nuclear parameter obtained by automated image analysis may be helpful in
      the differential diagnosis between neoplastic and non-neoplastic urinary bladder
      disease and correlate fairly with the classic histologic grading of malignancy in
      transitional cell carcinoma of the urinary bladder.

PMID- 7511283
TI  - [Effect of various cytologic preparation techniques on form, texture and
      densitometric nuclear parameters of normal and dysplastic bladder urothelial
      cells].
AB  - An important prerequisite for densitometric and morphometric measurements on
      cytological specimens is the standardized cell preparation. Optimal results can
      only be achieved when the analyses are carried out on a regular monolayer of cell
      nuclei. Comparing the conventional cytological smear with a new centrifugation
      technique we demonstrate statistically significant differences of the two methods
      in texture, size and parameters describing the DNA content of normal and
      dysplastic urothelial cells.

PMID- 7511284
TI  - [Value of cytometric parameters the planning of therapy of urothelial carcinoma].
AB  - The prognostic value of cytometric DNA parameters and their possible influence on
      the planning of treatment were investigated in 44 patients with transitional
      carcinoma of the urinary bladder (17 G1 tumours, 15 G2 tumours, 12 G3 tumours) as
      compared with normal urothelium of 7 patients. The nuclear DNA content was
      measured by scanning cytophotometry in Feulgen stained cytological smears. A
      statistically significant correlation was found to exist between the combination
      of the DNA parameters stem line quotient, 5c exceeding rate and DNA malignancy
      grade and the appearance of recurrences. A discrimination of a low grade and a
      high grade tumour group was based on this result within the G1 and the G2
      transitional carcinomas as well. All patients with a carcinoma classified as low
      grade were recurrence-free within an observation period of more than 10 years.
      Further studies should clarify if this group can be treated without a topic
      chemotherapy after transurethral electroresection in contrast to the high grade
      group in which a topic chemotherapy is necessary.

PMID- 7511286
TI  - [Ki-67 fraction, p53 alteration and numerical chromosome aberrations (chromosomes
      7 and 17) in formalin fixed bladder tumors].
AB  - p53 gene function and tumor cell proliferation are thought to be important
      parameters for tumor progression in bladder cancer. In this study
      immunohistochemistry and fluorescence in situ hybridization were used to
      determine the relationship between p53 alterations, tumor proliferation (Ki-67
      Labeling Index), and numerical chromosomal aberrations in formalin fixed bladder
      tumors. p53 expression was associated with Ki-67 LI (p = 0.0014), polysomy 17 (p
      = 0.001) and polysomy 7 (p = 0.0241). This is further evidence for a significant
      role of the p53 gene in proliferation control and preservation of genomic
      stability.

PMID- 7511288
TI  - [Monoclonal antibodies (MIB 1, PC 10, 486p and p53) as prognostic factors for
      recurrent urothelial carcinoma of the urinary bladder].
AB  - Using an immunohistochemical method expression of PCNA, Ki-67, 486p and p53
      antigen was investigated in paraffin sections of 119 patients with primary
      transitional cell carcinoma of the bladder. The purpose of this study was to
      detect recurring G1 and G2 bladder tumours compared with non-recurrent tumours. A
      relative large fraction of labelled cells for PCNA and Ki-67 was found in
      recurring G1 and G2 carcinomas. Moreover, recurrent transitional cell carcinomas
      showed a more positive staining pattern for 486p and p53, in contrast to non
      recurrent carcinomas. Immunohistochemistry of these four antigens seems to yield
      additional information about the possibility of recurrence in G1 and G2 bladder
      carcinomas, thus allowing early, i.e. more aggressive, therapy.

PMID- 7511287
TI  - [Morphometric, cytochemical and immunohistochemical studies on the proliferative
      activity of urinary bladder carcinomas].
AB  - 58 carcinomas of the urinary bladder as well as 11 carcinomata in situ and 10
      biopsies of normal mucosa were investigated for their proliferative activity by
      means of nuclear area morphometry, silver staining of nucleolar organizing
      regions (NOR) and immunohistochemical staining of the proliferating cell nuclear
      antigen (PCNA) and the Ki67 antigen. In comparison to normal bladder mucosa, the
      values were increased significantly (p < 0.05) in all carcinomata in situ and
      carcinomas. Within the carcinomas, there was an increase from G1- to G3
      carcinomas. For all four parameters, the values of the carcinomata in situ and
      the G2-carcinomas were similar. All parameters correlated with each other and
      allowed a significant differentiation between G1- and G2-carcinomas (p < 0.05),
      whereas they allowed only a less optimal differentiation between G2- and G3
      carcinomas. Of all markers of proliferation, the Ki67 antigen was the most useful
      criterium to differentiate between invasive and noninvasive carcinomas. A Ki67
      index of 30% seems to be a borderline between these two groups. This could be of
      prognostic relevance especially for the heterogeneous G2-carcinomas.

PMID- 7511285
TI  - [Significance of AgNOR analysis of urothelial carcinomas].
AB  - Biopsies of normal and atypical/dysplastic epithelium of the urinary bladder as
      well as transitional cell carcinomas grades I to III were stained with a silver
      nitrate solution, and the silver-stained nucleolar organizer regions were
      evaluated. The AgNOR-analysis shows highly significant differences in the G II
      subgroups, similar to the results of nucleolar subgrading. Because of the
      significantly differing 5-year survival rates, it can be justified to divide
      transitional cell carcinomas into two groups: a low-risk group with favorable
      prognosis (G Ia to G IIa), and a high-risk group with poor prognosis (G IIb to G
      IIIa,b).

PMID- 7511289
TI  - [Proliferative activity and p53 expression in transitional cell carcinoma of the
      urinary bladder].
AB  - Mutations of the p53 gene are important mechanisms in malignant transformation
      and are associated with dysregulation of normal cell growth. In the present study
      the expression of mutated p53-protein and proliferating cell nuclear antigen
      (PCNA) was investigated in a series of 31 human transitional cell carcinomas
      (TCC) by immunohistochemistry (IHC). The number of PCNA-positive cells and the
      pattern of expression was distinct in normal urothelium being confined to the
      basal cell layer. In dysplastic urothelium and in Carcinoma in situ (CIS) PCNA
      immunoreactive nuclei were irregularly distributed throughout all layers. In
      tumor cell complexes the pattern of PCNA-immunoreactivity was different in
      papillary and primary infiltrating TCCs. Densitometric quantification of the
      intensity of the PCNA-reactivity using image analysis revealed an increase from
      normal to dysplastic urothelium and from dysplastic urothelium to invasive
      tumors. 21/31 (68%) of the tumors and tumor-associated CIS showed overexpression
      of p53 varying in percentage, pattern and reaction intensity. The percentage of
      PCNA-positive cells was higher in tumors overexpressing p53. Double IHC showed
      colocalization of both molecules in a significant proportion of tumor cells
      suggesting a link of p53 overexpression and the abnormal proliferative activity.
      The present results show that p53 over-expression is found in a significant
      percentage of TCCs and indicate a close association with a defective growth
      regulation resulting in increased PCNA-levels and enhanced cellular
      proliferation.

PMID- 7511290
TI  - [Demonstration of gene amplification in urinary bladder cancer by fluorescent in
      situ hybridization (FISH)].
AB  - Fluorescence in situ hybridization (FISH) allows visualization of chromosomes and
      genes in interphase nuclei. Dual labeling FISH with probes for a gene of interest
      and the corresponding centromere can be used to determine chromosomal deletion
      and gene amplification. In case of a deletion less gene signals than centromere
      signals are found. In case of amplification gene signal number is distinctly
      increased as compared to centromere signals. To study gene amplification in fresh
      and formalin fixed bladder cancer we used gene specific probes for erbB-2, EGF-r,
      and 11q13 (bcl-1, PRAD1) together with their corresponding centromere probes
      p17H8, p7alphaTET and plC11A. Amplification was seen in 10/140 tumors for erbB-2,
      in 5/107 tumors for EGF-r, and in 15/137 tumors for 11q13. Different patterns of
      amplification suggested that FISH allows distinction of intrachromosomal
      (amplified genes in clusters) and extrachromosomal amplification (diffuse
      distribution of signals).

PMID- 7511291
TI  - [Molecular biological mechanisms in prostatic neoplasms].
AB  - An overview is given on three topics of prostate carcinoma: 1. New data on
      genetic factors in the pathogenesis, 2. molecular activation mechanisms in
      metastasis and 3. endocrine dedifferentiation during the course of the disease
      causing androgen independent state. Recent epidemiological analyses have clearly
      shown, that a specific part of prostate cancer is inherited. By DNA-interphase
      analyses specific allelic losses have been demonstrated. Metastatic progression
      is both associated with oncogene ras activation and chromosomal deletions.
      Endocrinological dedifferentiation cannot be simply explained by an overgrowth by
      androgen-receptor negative tumor cells, but by a more complex deregulation with
      strong influences by stromal-epithelial interactions. Downregulation of the
      promoter region of the androgen receptor may play a crucial role in the
      development of "endocrine deafness".

PMID- 7511292
TI  - [p53 mutation in phenacetin-induced urothelial carcinomas].
AB  - We investigated 16 urothelial carcinomas from 13 patients with evidence of
      phenacetin abuse for p53 mutations by single-strand conformation polymorphism
      (SSCP) analysis and direct DNA sequencing. p53 mutations were detected in 8 of 14
      primary tumors (57%). Missense mutations were located in exon 5 (3 mutations),
      exon 6 (1), exon 7 (2) and exon 8 (1). An insertion of a single cytosine in exon
      5 was detected in a bladder tumor and its lung metastasis. In one patient,
      urothelial carcinomas in the renal pelvis and in the ureter exhibited two
      different mutations, strongly suggesting that these tumors developed
      independently. In contrast, the tumors in the renal pelvis and bladder of another
      patient contained the same mutation, indicating intracavitary metastatic spread.
      Our data support the view that phenacetin causes urothelial carcinomas through
      chronic tissue damage rather than promutagenic DNA lesions.

PMID- 7511293
TI  - [Distribution pattern of urothelial associated glycoproteins in human bladder
      cancer cell lines in in vitro culture].
AB  - The distribution of four antibodies against urothelial-associated glycoproteins
      (UAGAb: Uro1, -5, -9, -10, SIGNET) was studied by dual parameter flow-cytometry
      (UAGAb and DNA staining) in normal non-urothelial cancer cell lines (2), normal
      urothelial cell lines (2) and bladder cell lines (5). When cell lines were
      compared as plateau monolayers, high proportions of Uro1 and Uro10 were found in
      all cell lines, in contrast to Uro5 and Uro9, both showing specificity for
      urothelial cells. Though being described as a pan-urothelial marker, Uro5 is not
      found in all cell lines. In two cell lines (RT4 and J82) three different growth
      states (exponential and plateau monolayer and multicellular spheroids were
      compared, and dependence on spatial configuration could be shown for Uro9. Cell
      cycle relation of expression was found for Uro1 and Uro10.

PMID- 7511295
TI  - [Spectrum of morphologic findings in cystectomy specimens].
AB  - A report of 64 cystectomy specimens is presented with emphasis on the macroscopic
      tumor pattern of the urinary bladder carcinoma. From gross observations bladder
      cancer gives a wide spectrum: unifocal or multiple papillary, mostly superficial
      carcinomas, nodular tumors more or less deeply invading the bladder muscle, flat
      carcinomas, widespread diffuse carcinomas with infiltration of the whole bladder
      wall, flat ulcers with or without tumor rest after TUR, and tumors almost filling
      the whole bladder and destroying the bladder wall; miscellaneous tumours were
      also observed. In 3 cases bladder cancer arose from the lumen of one or more
      diverticula. This study describes the features presented at the time that
      patients underwent radical cystectomy in early as well as in advanced stages.

PMID- 7511294
TI  - [Uroplakin III, a specific membrane protein of urothelial umbrella cells, as a
      histological markers for metastatic transitional cell carcinomas].
AB  - We have investigated, by immunohistochemical staining of various paraffin
      embedded carcinoma sections, the tissue-specific expression of uroplakin III--a
      recently characterized constituent glycoprotein (47 kD) of the asymmetrical unit
      membrane which forms plaques on apical surface of urothelial umbrella cells. The
      apical membrane pattern of normal urothelial umbrella cells was in part
      maintained in papillary transitional cell carcinomas (TCCs). In addition, in both
      papillary and invasive TCCs, variously sized lumina exhibited positive membrane
      staining of uroplakin III. In some cases, basal cell membrane staining was seen.
      Positive reactions (which sometimes were very focal) were noted in 16/18
      papillary non-invasive TCCs (89%), 21/37 invasive TCCs (57%) and 12/15 TCC
      metastases (80%). Non-TCC carcinomas of different origin (n = 63) were
      consistently negative. These results show that uroplakin III may serve as a
      useful marker for TCCs, revealing specific urothelial differentiation features to
      be expressed in such tumors even after metastasis. This marker, while of only
      intermediate sensitivity, is highly specific, thus opening interesting
      histodiagnostic possibilities in the case of unclear carcinoma metastases.

PMID- 7511296
TI  - [AP-2: a nuclear effector of malignant transformation by ras oncogene].
AB  - We have applied a series of cell clones established from the human
      teratocarcinoma cell line PA-1 to study the effect of malignant transformation by
      ras-oncogenes on the regulation of cell growth and differentiation. A particular
      aim of this study was to identify nuclear gene-regulatory factors that are
      affected by ras-transformation. We show that a key nuclear target of ras is the
      transcription factor AP-2. AP-2 function is inhibited through the ras-controlled
      signal transduction cascade by at least two different mechanisms, i.e. inhibition
      of an AP-2 coregulatory factor and by expression of an alternatively spliced
      inhibitory AP-2 protein.

PMID- 7511298
TI  - [Pathogenesis of autoimmunity in thymoma].
AB  - The analysis of thymic epithelial tumors (TET) with and without myasthenia gravis
      (MG) has identified both a residual organotypic differentiation of TETs and the
      aberrant expression of acetylcholine receptor (AChR)-epitopes in TET epithelial
      cells to be associated with MG. These findings have suggested an abnormal
      selection of helper T cells as a mechanism of paraneoplastic MG. Here we show by
      electronmicroscopy that epithelial cells of TETs and normal thymus exhibit the
      morphological features (autophagic vacuoles) thought to be necessary to process
      endogenous proteins for presentation by MHC class II molecules to immature T
      cells.

PMID- 7511300
TI  - [Pattern of expression of integrins in alveolar epithelia of fetal and adult
      lungs and interstitial lung diseases].
AB  - We studied the expression of integrin alpha and beta chains on alveolar epithelia
      in normal and fibrotic lung tissue by immunohistochemistry. Alveolar epithelia
      and their precursor cells in fetal lung tissue consistently expressed alpha 1,
      alpha 2, alpha v and beta 1 chains. Neoexpression of alpha 4, alpha 6 and beta 4
      chains was detected on alveolar epithelia of fibrotic lung tissue. Adhesion
      blocking assays with isolated type II pneumocytes were performed to investigate
      the substrate specificity of the alpha chains. alpha 1, alpha 2 and alpha 3
      demonstrated a specificity for collagen, alpha 4, alpha 5 and alpha 6 for
      fibronectin, alpha 3 and alpha 6 for laminin and finally alpha 5 and alpha v for
      vitronectin.

PMID- 7511297
TI  - [Occurrence of CD44 and its isoforms under orthological and pathological
      conditions].
AB  - Variant isoforms of CD44 have been strongly implicated in malignant
      transformation and cancer metastasis. To ascertain the pattern of expression of
      these isoforms in human normal, fetal and tumor tissues (breast carcinomas, renal
      cell carcinomas, malignant melanomas, colon carcinomas, non-Hodgkin-lymphomas,
      neuroblastomas and brain tumors), we generated monoclonal antibodies against CD44
      variant regions. Monoclonal antibodies were produced against variant regions
      encoded by exons 4v, 6v and 9v. CD44 variant isoforms are expressed on normal
      epithelial cells in a different pattern. Regions of epithelia that expressed the
      highest levels of the variant isoforms were those with a high rate of cell
      division. CD44 variant isoforms were not expressed by all investigated tumors
      (not by malignant melanomas, brain tumors and neuroblastomas). It is interesting
      that the expression of CD44 isoforms in non-Hodgkins lymphomas and colon
      carcinomas shows possibly a correlation with malignancy.

PMID- 7511299
TI  - [Anti-human collagenase type IV expression in preneoplastic lesions and early
      squamous cell lung carcinoma].
AB  - Proteolytic enzymes like collagenase type IV are relevant to the destruction of
      matrix-components within the scope of invasive tumor growth. Preneoplastic
      lesions of the bronchial mucosa and early squamous cell carcinomas were
      investigated immunohistochemically using anti-human-collagenase type IV
      monoclonal antibodies due to the question of enzymatic proteolysis of basement
      membrane structures. With increasing malignant epithelial transformation an
      increase of collagenase type IV expression was observed in single atypical cells
      of severe dysplasia, carcinoma in situ and early cancer of the bronchus.
      Collagenase type IV expression can be evaluated as enhanced proteolytic potency
      for degradation of matrix structures of the basement membrane as one factor for
      early infiltration in preneoplastic lesions up to early squamous cell carcinomas
      of the lung.

PMID- 7511301
TI  - [Pulmonary and pleural reaction patterns to artificial mineral fibers -
      rockwool].
AB  - Epidemiological and animal studies about the fibrogenic and carcinogenic
      properties of natural mineral fibers required the development of man made
      vitreous fibers as substitutes for asbestos containing material. The question
      about the possible fibrogenic and carcinogenic properties of man-made vitreous
      fibers is not yet answered. By means of different experimental animal studies we
      tried to investigate the man made vitreous fibers-related pulmonary and pleural
      diseases. The experimental administration of rockwool induce lesions in the lung
      of the rats. The lung showed an extensive granulomatous inflammation. In the
      observation time of 10 months we did not find any malignant tumor of the lung and
      the pleura.

PMID- 7511304
TI  - [List of members].

PMID- 7511303
TI  - [Pathology of prostatic carcinoma: new approaches to its development and
      biological significance].
AB  - The common prostatic carcinoma consists of two different types with respect to
      development, spread, histopathology, morphogenesis and prognosis. These are the
      carcinoma of the dorso-peripheral zone and the tumor which is located in the
      antero-central zone. The first one corresponds to the clinically manifest
      prostatic carcinoma, the latter is identical to the prostatic carcinoma
      incidentally found by the pathologist examining unsuspicious prostatic tissue
      from transurethral resection or simple prostatectomy. The antero-central tumor
      growths to the ventral area and infiltrates the apex and bladder neck frequently.
      It is biologically not as important as the tumor of the dorso-peripheral zone
      showing a lower grade of malignancy in the majority of cases. In 2 of 3 cases,
      however, there are one or more coexisting carcinomas in other, frequently dorso
      peripheral zones. Therefore the risk of the individual patient can not precisely
      be estimated. The carcinoma of the dorso-peripheral zone does predominate by
      frequency and biological potency. The incidence of positive lymph nodes strongly
      increases when seminal vesicle invasion is found. The disturbance of the
      epithelial-stromal interaction is the starting point of carcinogenesis. In the
      first step, PIN results of an intraductal proliferation of atypical epithelial
      cells, whereas atypical hyperplasia develops from an overwhelming proliferation
      of tubular glands with progressive decrease of basal cells. Based on the
      topographical and histological relationships the role of PIN as a precursor
      lesion of the dorso-peripheral prostatic carcinoma is considered, whereas
      atypical hyperplasia is thought to represent the preneoplastic state of the
      incidental and antero-central prostatic carcinoma, respectively.

PMID- 7511302
TI  - [New aspects in histogenesis of hyperplasia and cancers of the prostate].
AB  - The prostatic epithelium has generally been described as consisting of three
      separate cell types--secretory, luminal, basal and endocrine-paracrine (EP) cells
      -that differ by their morphological features, functions and hormonal regulation.
      Compared with the gastrointestinal tract and other self-renewing tissue, little
      is known about differentiating and proliferative processes in the normal and
      hyperplastic human prostate. In the present report, we propose a stem cell model
      for the organization of the prostatic epithelium that may explain normal and
      abnormal growth in the human prostate. This model is based on recent data
      indicating that 1. the three basic cell types encountered in the prostatic
      epithelium are linked in precursor-progeny relationship as documented by the
      existence of intermediate phenotypes, 2. the basal cell layer represents the
      proliferative compartment in normal and hyperplastic conditions, 3. EP-cell types
      do not proliferate and lack the nuclear androgen receptor (AR), 4. basal cells
      may be potentially androgen-responsive as documented by the presence of AR, 5.
      formation of basement membrane (BM) deposits is crucial in the development of the
      invasive phenotype. In this model, a small stem cell population located in the
      basal cell layer gives rise to all epithelial cell lineages encountered in the
      normal, hyperplastic and neoplastic prostate. The differentiating process from
      basal cells to secretory luminal cells via intermediate phenotypes is induced by
      circulating androgens, and largely depends on the presence of responsive target
      cells in the basal cell layer. Accordingly, the abnormal growth of the secretory
      epithelium in benign prostatic hyperplasia may be related to an increase in the
      total number of androgen-responsive basal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511305
TI  - [Pathological findings of the prostate and their consequences: a critical view].

PMID- 7511306
TI  - [Three-dimensional spatial texture of adenocarcinoma of the prostate by a
      combination of stereology and digital image analysis].
AB  - Second-order stereology combines stereology with stochastic geometry and digital
      image analysis to obtain an insight into the spatial architecture (texture) of
      tissues. In twenty radical prostatectomy specimens from patients with invasive
      adenocarcinomas of the prostate gland, the pair correlation function of the
      epithelial tissue component was estimated both for the carcinomatous and the
      tumour-free domains. After interactive segmentation of the gray level images, the
      method works fully automatically. The mean pair correlation function of
      carcinomatous tissue shows less clustering of epithelium at short distances and
      less rhythmicity of epithelium at long distances as compared to tumour-free
      tissue. This loss of glandular integrity is higher in cribriform than in tubular
      carcinomas. The results suggest that second-order stereology is a powerful tool
      for the objective evaluation of glandular differentiation.

PMID- 7511307
TI  - [Atypical hyperplasia of the prostate: coincidence with invasive carcinoma. A
      study of 69 prostatectomy preparations].
AB  - In a series of 69 prostatectomy specimens, including 62 invasive carcinomas, we
      studied the prevalence of atypical hyperplasia of small acinar, large acinar and
      cribriform type, diagnosed according to the criteria of J. Kovi, 1989. The study
      was performed on serial whole sections of 5 mm thick slices. As a result, the
      association of atypical large acinar hyperplasia with small acinar or cribriform
      atypical hyperplasia was significantly increased in cases with coincidental
      carcinoma. Furthermore, atypical cribriform hyperplasia was almost exclusively
      found in cases with cribriform or solid type of invasive carcinoma.

PMID- 7511308
TI  - [Prognostic significance of prostatic carcinoma grading according to Helpap].
AB  - The prognostic significance of the subgrading system introduced by Helpap was
      retrospectively examined in 342 prostatic carcinomas, revealing a distinct
      decrease on survival rate with increasing grade of malignancy: during the first
      three years following diagnosis 21 per cent of the patients with carcinomas
      graded as Ib died, while all patients with grade Ia carcinomas were still alive.
      Thus, according to our results, a clinical observation, but no further surgical
      treatment is recommended in grade Ia cases. At the time of diagnosis, 54.3 per
      cent of our cases were at the stages T3 or T4. 15.4 per cent of the carcinomas
      were incidental. The majority (52 per cent) of these cases had to be graded as Ia
      or Ib, but only 14.8 per cent of the non-incidental tumors did belong to these
      prognostically most favourable groups. In summary, the prostate carcinoma grading
      system introduced by Helpap is characterized by prognostic significance and good
      reproducibility, and thus should be part of the routine diagnosis of prostate
      carcinoma.

PMID- 7511311
TI  - [Determination of proliferation activity of prostate cancers by means of nuclear
      proliferation-associated formalin resistant Ki-S5 antigens].
AB  - In order to evaluate the growth fraction in normal, hyperplastic and neoplastic
      prostatic tissue, we examined paraffin sections of 55 cases of prostatic cancer
      containing areas of benign (BPH) and atypical hyperplasia (AH). Cellular
      proliferation was assessed by nuclear staining with the monoclonal antibody Ki-S5
      directed against a formalin-resistant epitope of the Ki67 antigen. The
      proliferation rate was minimal in normal glands and BPH (mean 0.35%), rather low
      in AH and grade I carcinoma (0.5 to 15% compared to grade II carcinoma (1 to 40%)
      and peaking to near 80% labeled cells in grade III carcinoma. In the majority of
      the tumors, foci of increased cell growth could be detected by this method. Ki-S5
      labeling indices correlated significantly with the histopathologic grading
      established by Dhom. Correlation with the clinical outcome will be the subject of
      subsequent retrospective studies.

PMID- 7511310
TI  - [AGNOR analyses of prostate carcinomas of high and malignancy].
AB  - Biopsies of normoglandular prostate, of hyperplastic-atypical/preneoplastic
      prostate and of prostatic carcinomas of different grades of malignancy were
      stained according to the method described by Crocker and Ploton in order to
      demonstrate the silver stained nucleolar organizer regions (AgNORs). The AgNOR
      values per unit area of nucleus were compared to the nucleolar status. Increased
      grade of malignancy corresponds to an increase in the number of AgNORs per unit
      area of nucleus. Significant differences in the AgNOR values exist particularly
      in the subgroups of grade II of malignancy, as well as between grades G Ia
      through G IIa vs. G IIb through G III. Differentiating prostatic carcinoma into
      low and high states of malignancy is important not only for prognosis, but also
      for the therapy, since, when tumor-biological aspects are considered, a radical
      prostatectomy is no longer indicated in patients with highly malignant
      carcinomas.

PMID- 7511312
TI  - Z-RNA. The synthesis of 2'-O-[13C]methyl- and 5-methyl-analogs of ribo-CGCGCG.
AB  - Chemical synthesis of 2'-O-[13C]methyl-rCGCGCG and 5-methyl-rCGCGCG using support
      aided phosphoramidite method is presented. 2'-O-Methyl guanosine derivative was
      separated from its 3'-O-methyl counterpart using transient 5',3'-O-silylation
      with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (Markiewicz reagent). The
      hexamers were obtained in a purity suitable for NMR studies.

PMID- 7511309
TI  - [Prostate cancers and potential precancerous conditions: DNA cytometric
      investigations and interphase cytogenetics].
AB  - The topic of this investigation was to compare precancerous lesions of the
      prostate (prostatic intraepithelial neoplasia -PIN- and atypical hyperplasia -AH
      ) and invasive carcinomas concerning DNA ploidy (image cytometry/ICM) and
      morphologically feasible chromosomal aberrations (interphase cytogenetics/NISH).
      The aim was to find clues to formal pathogenesis of prostatic cancer. Prostatic
      tissue of 76 patients (76 areas with carcinoma, 71 with PIN, and 12 with AH) was
      examined by means of ICM. In 44 cases of coincidental PIN and carcinoma, the
      gradings of PIN and carcinoma correlated. C-values, 2,5c-exceeding-rate, and
      aneuploidy rate turned out to increase in PIN and carcinoma with increasing
      grading (P < 0.01). In some of these cases NISH was carried out in serial
      sections by applying centromer-(X,Y,1,7,8,10,17,18) and telomer-(1p) specific DNA
      probes. The result of this approach was an increase in the number of chromosomal
      aberrations and chromosomes involved correlating with the grading. Our conclusion
      is that PIN 1 could be regarded as the precancerous lesion mainly to higher
      differentiated carcinomas, whereas PIN 2 and 3 should be considered a
      preneoplastic condition mainly of moderately and low differentiated carcinomas.

PMID- 7511313
TI  - [Circulatory hyperkinesis of cirrhosis: etiopathogenesis, clinical and
      therapeutic implications].
AB  - A mysterious complication of cirrhosis is the progressive development of a
      hyperdynamic circulatory state characterized by high cardiac output and low
      peripheral and splanchnic arterial resistance. This particular hemodynamic state
      plays a major role in the progress of portal hypertension and sodium renal
      retention observed in cirrhosis. In this review, we try to better define the
      clinical impact and the etiopathogenic mechanism of the hyperdynamic state of
      cirrhosis.

PMID- 7511314
TI  - Oculomotor nerve palsy associated with vincristine treatment.

PMID- 7511315
TI  - Neurofilament reorganisation and neurofilament antigen redistribution in spinal
      motoneurones following retrograde axonal transport of diphtheria toxin.
AB  - Single unilateral injections of diphtheria toxin (DTX) into the external anal
      sphincter muscle or internal intercostal nerve of cat induced characteristic
      ultrastructural lesions in corresponding ipsilateral spinal motoneurones 6-8 days
      later. The chief neuronal lesion was a progressive disruption of Nissl body
      composition and organisation, which between days 8-19 post injection was
      accompanied by a progressive accumulation of neurofilaments in motoneuronal
      perikarya and dendrites. Some axons in the ipsilateral ventral horn became
      hypertrophied due to neurofilamentous accumulation. Related immunocytochemical
      investigations 6-35 days after injection of DTX revealed abnormal
      immunoreactivity intoxicated motoneurones for 200-kDa and 160-kDa phosphorylated
      neurofilament proteins, but not in contralateral motoneurones. By day 35 abnormal
      neurofilament immunostaining also occurred in ipsilateral and some contralateral
      interneurones but not contralateral motoneurones. Abnormalities of Nissl body
      endoplasmic reticulum, neurofilament organisation, and neurofilament protein
      immunostaining were identical after either intraneural and intramuscular
      injections of DTX, indicating abnormalities were attributable to toxicity and not
      injection-related axonal damage. Since DTX acts specifically in the soma to
      inhibit protein synthesis, neurofilament abnormalities are secondary to
      cytotoxicity and probably result from deficits in transference of existing
      partially phosphorylated neurofilaments to the axonal transport system, or axonal
      transport per se.

PMID- 7511317
TI  - Tomaculous neuropathy in chromosome 1 Charcot-Marie-Tooth syndrome.
AB  - We performed morphological and immunohistochemical studies on sural nerve
      biopsies from two members of a Charcot-Marie-Tooth type 1B family, in which a
      mutation of the P0 gene on chromosome 1 had been found. Biopsies showed a
      tomaculous neuropathy with loss of myelinated fibers and frequent small onion
      bulbs. Immunofluorescence with antibodies to P0 showed this protein to be present
      in tomaculous and non-tomaculous areas of the myelin sheath. The severity of the
      myelin abnormalities suggests that in this family Charcot-Marie-Tooth disease may
      result from a generalized disturbance of Schwann cells as a result of an abnormal
      P0 protein.

PMID- 7511318
TI  - Psychopathology and family functioning in mothers with epilepsy.
AB  - In a prospective comparative study of children born to mothers with epilepsy and
      to healthy controls, maternal psychopathology, family functioning and the effects
      of maternal psychopathology and family functioning on child mental status were
      investigated. The instruments used were the Present State Examination (PSE), the
      Past History Schedule (PHS), a psychiatric interview for preschool children and a
      structured interview about family functioning. Interviewers were blind to the
      clinical status of the mother. The group of mothers with epilepsy differed from
      the control group only regarding a higher prevalence of minor psychopathology and
      in 1 of 4 areas of family functioning. There was no difference between mothers
      with epilepsy and the control group regarding major psychopathology, and almost
      no differences regarding family functioning. The effect of maternal
      psychopathology on child mental status was mediated by disturbed family
      functioning only in the epilepsy group.

PMID- 7511316
TI  - Ki-67 immunoreactivity in human central nervous system tumors: a study with MIB 1
      monoclonal antibody on archival material.
AB  - Paraffin-embedded surgical specimens from 136 primary human central nervous
      system (CNS) tumors, including 50 meningiomas, 24 astrocytomas, 26 anaplastic
      astrocytomas, 9 glioblastomas, 8 oligodendrogliomas, 4 ependymomas, 1 anaplastic
      ependymoma, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were
      immunostained, following microwave processing, using a streptavidin/peroxidase
      method and the MIB 1 monoclonal antibody (mAb) against the Ki-67 antigen. The
      following mean Ki-67 labeling index (LI) values +/- SD were found: meningiomas,
      2.47 +/- 1.83; astrocytomas, 2.03 +/- 2.03; anaplastic astrocytomas, 12.80 +/-
      6.29; glioblastomas, 14.57 +/- 6.77; oligodendrogliomas, 5.06 +/- 4.78;
      ependymomas, 2.63 +/- 2.58; anaplastic ependymoma, 6.89; subependymomas, 1.79 +/-
      1.54; medulloblastomas, 18.77 +/- 9.65; and paragangliomas, 2.19 +/- 2.51. Our
      findings indicate that while malignant CNS tumors always exhibited high Ki-67 LI
      values, and benign CNS tumors generally displayed lower values, increased
      immunoreactivity for Ki-67 epitopes (Ki-67 LI higher than 4) was noted in a
      number of meningiomas, astrocytomas, ependymomas, oligodendrogliomas and
      paragangliomas, contrasting with their benign histological features. Further
      investigations of the Ki-67 immunoreactivity in CNS tumors and systematic
      correlation with the postoperative follow-up of patients are necessary to
      determine the value of Ki-67 LI in predicting the biological behavior of CNS
      neoplasms.

PMID- 7511320
TI  - A ribozyme model: site-specific cleavage of an RNA substrate by Mn2+.

PMID- 7511319
TI  - Injection of bovine parathyroid poly(A)+ RNA into Xenopus oocytes confers
      sensitivity to high extracellular calcium.
AB  - Parathyroid cells detect increments in the extracellular [Ca2+], which lead to
      substantial increases in intracellular free Ca2+ ([Ca2+]i) and, ultimately, to
      suppression of parathyroid hormone (PTH) secretion. To determine whether mRNA
      from parathyroid tissue could confer sensitivity to high extracellular Ca2+, we
      isolated and injected total bovine parathyroid poly(A)+ RNA into Xenopus laevis
      oocytes. To assess translational activity of the RNA, PTH released into the media
      was measured. Intact PTH was detected in the medium for < or = 48 h, and
      injection of increasing amounts of RNA (approximately 0.5-50 ng/oocyte) led to
      the release of greater quantities of PTH. We screened for the expression of a
      putative Ca2+ sensor molecule by measuring 45Ca efflux from preloaded oocytes, in
      response to raising extracellular [Ca2+] from 0.7 to 5.7 mM. This increment in
      [Ca2+] stimulated 45Ca efflux by 249 +/- 52 cpm over 20 min from eggs injected
      with parathyroid poly(A)+ RNA (n = 22). This response was significantly greater
      than 45Ca efflux from any group of controls exposed to the same change in
      extracellular Ca2+ (p < 0.02), including oocytes injected with either water, cRNA
      for the platelet-derived growth factor (PDGF) BB receptor, or T cell poly(A)+
      RNA. Size-fractionation of poly(A)+ RNA over sucrose gradients demonstrated that
      mRNA, which induced responsiveness to high extracellular Ca2+, was present in
      fractions with transcripts of approximately 5-9 kB. Injection of these fractions
      also conferred sensitivity to the presence of Ba2+ or Sr2+ (both at 5 mM) in the
      media.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511321
TI  - Artificial ribonucleases.
AB  - Many inorganic and organic compounds promote the reactions catalyzed by RNase A.
      Both the transesterification step, where a 2',3'-cyclic phosphate is formed with
      concomitant cleavage of RNA, and the hydrolysis step, where the 2',3'-cyclic
      phosphate is converted to a phosphate monoester, may be mimicked with compounds
      that are readily synthesized in the laboratory. Electrophilic activation of the
      phosphate ester and charge neutralization are generally important means by which
      artificial RNases promote phosphate diester displacement reactions. Several
      artificial RNases operate by a bifunctional general acid/general base mechanism,
      as does RNase A. Provision of an intramolecular nucleophile appears to be an
      important pathway for metal complex promoted phosphate diester hydrolysis. In
      contrast to the successful design of compounds that promote the reactions
      catalyzed by RNase A, there are no artificial nucleases to date that will cleave
      the 3' P-O bond of RNA or hydrolyze an oligonucleotide of DNA. Artificial RNases
      based on both metal complexes and organic compounds have been described. Metal
      complexes may be particularly effective catalysts for both transesterification
      and hydrolysis reactions of phosphate diesters. Under physiological conditions
      (37 degrees C and neutral pH), several metal complexes catalyze the
      transesterification of RNA. Future work should involve the development of metal
      complexes which are inert to metal ion release but which maintain open
      coordination sites for catalytic activity. The design of compounds containing
      multiple amine or imidazole groups that may demonstrate bifunctional catalysis is
      a promising route to new artificial RNases. Further design of these compounds and
      careful placement of catalytic groups may yield new RNase mimics that operate
      under physiological conditions. The attachment of artificial RNases to
      recognition agents such as oligodeoxynucleotides to create new sequence-specific
      endoribonucleases is an exciting field of endeavor. Applications for such
      sequence-specific endoribonucleases include in vitro manipulations of RNA and the
      destruction of gene transcripts in vivo. Further work will require the
      development of new synthetic methodologies for attachment of catalytic cleaving
      groups to oligodeoxynucleotides.

PMID- 7511323
TI  - Current status of PSA in the management of prostate cancer.

PMID- 7511325
TI  - Intra-arterial chemotherapy for palliation of fungating breast cancer. A case
      report and review of the literature.
AB  - The infusion of chemotherapy into arteries that feed locally advanced tumors has
      theoretical appeal, since the tumor mass may be exposed to high drug
      concentrations with administration of reduced or conventional doses of
      chemotherapy. Experience in applying this technique to patients with breast
      cancer in the United States is limited. Locally advanced, fungating breast
      cancers pose particularly difficult management problems for which intra-arterial
      drug delivery may be appropriate in carefully, selected cases. Disseminated
      cancer, physical deformity, foul odor, bleeding, and infection, as well as
      associated psychosocial factors, contribute to the complexity of caring for these
      patients. We report the case of a patient with a massive fungating breast cancer
      who was effectively palliated with intra-arterial administration of mitomycin,
      fluorouracil, cisplatin, and mitozantrone. The rapidity of our patient's response
      using this approach supports the observations of other investigators. We offer a
      review of the literature reporting the application of this technique for patients
      with locally advanced breast cancer. Further study of intra-arterial chemotherapy
      in carefully selected patients with locally advanced and fungating breast cancers
      is warranted.

PMID- 7511322
TI  - Medical management of prostatic diseases.
AB  - A variety of new pharmacologic agents has allowed expanded therapeutic options
      for men with benign prostatic hypertrophy as well as men with prostate cancer.
      Appropriate implementation of these agents requires an understanding of their
      mechanisms of action, as well as awareness of the underlying pathological
      processes. Medical therapy of BPH is less invasive than standard surgical
      intervention, but it carries the risks of missing clinically significant prostate
      cancers. In addition, medical treatment of BPH is less effective than
      prostatectomy; however, since symptomatic relief is usually the end point of
      treatment for BPH, medical therapy is successful for many men without the risks
      of surgery. The GnRH agonists (and GnRH antagonists to be developed) allow
      medical hormonal therapy to be implemented for men with symptomatic prostate
      cancer without the psychological effects of castration. Oral antiandrogens allow
      for a prompt blockade of androgen action on prostate cancer during GnRH agonist
      use, and they may improve longevity for some men with prostate cancer. The
      widespread use of these agents should be tempered by their relatively high costs
      with long-term use.

PMID- 7511324
TI  - Dextran-coated superparamagnetic iron oxide, an MR contrast agent for assessing
      lymph nodes in the head and neck.
AB  - PURPOSE: To investigate dextran-coated superparamagnetic iron oxide particles
      (BMS 180549) as an MR contrast agent for assessing lymph nodes. METHODS: Five
      different doses ranging from 0.3 to 1.7 mg Fe/kg were evaluated in five healthy
      human male subjects as part of a phase 1 clinical study. T1-, T2-, and proton
      density-weighted spin-echo images as well as multiplanar gradient-echo and
      spoiled gradient-echo images were acquired before and 1 hour, 4 hours, and 24
      hours after contrast administration. Image analysis was performed with visually
      selected regions of interest. Signal intensities were measured for neck lymph
      nodes and the adjacent muscle. Enhancement effects were evaluated as a function
      of dose, imaging time after contrast administration, and MR pulse sequence.
      RESULTS: The iron oxide particles were phagocytized by macrophages within the
      normal functioning lymph nodes, resulting in a dramatic decrease in signal
      intensity because of magnetic susceptibility effects. T2*-weighted gradient echo
      and T2-weighted spin echo showed significant decrease in the signal intensity of
      normal lymph nodes at 24 hours after contrast injection at a dose of 1.7 mg
      Fe/kg. No significant changes in lymph node signal intensity on T1-weighted spin
      echo images were noted at any dose or imaging time point. CONCLUSIONS: This
      preliminary clinical evaluation demonstrates intravenous delivery of an iron
      based contrast agent, resulting in negative enhancement of normal lymph nodes.

PMID- 7511326
TI  - Radiation tolerance of the transplanted liver. A histopathologic study in three
      cases.
AB  - Three patients with multifocal recurrence of hepatocellular carcinoma following
      liver transplantation received palliative irradiation. Hyperfractionated
      irradiation (150 cGy/fraction b.i.d.) was delivered in two cases to the entire
      liver using parallel opposed oblique portals to a total dose of 30 Gy.
      Conventional irradiation (180 cGy/fraction) totaling 45 Gy was administered to
      the liver hilus with concomitant infusional 5-fluorouracil chemotherapy in the
      third case. Clinicopathologic correlations were performed. At autopsy all
      patients had massive tumor burden within the liver. Veno-occlusive changes were
      observed in two patients 1 and 2 months following completion of conventional and
      hyperfractionated irradiation, respectively. Liver transplantation in these two
      patients had been performed 18 and 16 months prior to palliative hepatic
      irradiation. In the third patient, no veno-occlusive changes were pathologically
      observed at autopsy 1 month after completing hyperfractionated radiation, which
      was delivered 6 months following liver transplantation. No significant
      differences in prior immunosuppressive therapy were identified among patients.
      Veno-occlusive changes are not spared by hyperfractionated radiation.
      Transplanted livers exhibit responses to radiation similar to those normally
      observed.

PMID- 7511327
TI  - Carboplatin plus ftorafur as a palliative treatment in locally advanced cancer of
      the oral cavity and lip.
AB  - Forty consecutive patients with local advanced cancer of the oral cavity and lip,
      heavily pretreated, were palliated with two courses of carboplatin, 400 mg/m2
      intravenously once a month plus ftorafur, 500 mg/m2 daily per os for 30 days.
      Previous treatment consisted of surgery (17 patients), radiation therapy (23
      patients), and chemotherapy with cisplatin plus bleomycin (15 patients). The main
      sites of primary tumor were the tongue (12 patients), hard palate (6 patients),
      retromolar area (6 patients), tonsils (6 patients), perioral skin and lip (5
      patients), and floor of the mouth (5 patients). Complete response was observed in
      3 patients, and partial response in 7. Symptomatic improvement was observed in
      56% of the cases. Median duration of response was 9 months. Median survival was 7
      months. The main toxic effects were nausea (39 cases), vomiting (35 cases), and
      thrombocytopenia (4 cases). We conclude that carboplatin plus ftorafur has a role
      as palliative chemotherapy in cancer of the oral cavity and lip in heavily
      pretreated patients when local therapies are not suitable.

PMID- 7511328
TI  - Metastatic adamantinoma of bone to lung. A case report of the natural history and
      the use of chemotherapy and radiation therapy.
AB  - A patient with metastatic adamantinoma from the tibia is described, in whom the
      biologic behavior of the tumor and the clinical course that evolved was typical.
      Tumor regression was observed on two separate occasions to a combination
      chemotherapeutic regimen of etoposide plus cisplatin or carboplatin.

PMID- 7511329
TI  - Varying populations of CD59-negative, partly positive, and normally positive
      blood cells in different cell lineages in peripheral blood of paroxysmal
      nocturnal hemoglobinuria patients.
AB  - CD59-antigen expression on the surface membranes of erythrocytes, granulocytes,
      monocytes, lymphocytes, and platelets was determined by flow cytometry in 34
      healthy controls and 17 patients with paroxysmal nocturnal hemoglobinuria (PNH).
      In all PNH patients, CD59-negative erythrocytes accounted for > 10% of the total
      erythrocyte population. Two erythrocyte populations (CD59-negative and normally
      positive or CD59-negative and partly positive), three populations (CD59-negative,
      partly positive, and normally positive), and one population (CD59-negative) were
      demonstrated in ten, six, and one patients, respectively. However, CD59-negative
      granulocytes did not account for > 10% of the total granulocytes in two patients,
      and one of them had only a CD59 normally positive granulocyte population. A
      particular granulocyte population extended over both CD59-negative and partly
      positive areas was shown in two patients. Two populations (CD59-negative and
      normally positive) and one population (CD59-negative) were demonstrated in
      monocytes and lymphocytes. CD59-negative lymphocytes accounted for > 50% of the
      total lymphocytes in only two patients. Three patients had a CD59 normally
      positive lymphocyte population. Percentages of CD59-positive platelet population
      in normal controls were widely various. Therefore, it was usually difficult to
      discriminate between PNH-affected and normal platelets. Thus, the flow cytometric
      profiles of CD59-antigen expression varied not only between PNH patients but
      between cell lineages. The present results and our prior study indicate that CD59
      flow cytometry using erythrocytes and granulocytes is most suitable for
      diagnosing PNH.

PMID- 7511330
TI  - Transgenic mouse model of pharmacologic induction of fetal hemoglobin: studies
      using a new ribonucleotide reductase inhibitor, Didox.
AB  - Evaluation of pharmacologic agents that stimulate fetal hemoglobin production has
      been done mainly in baboons and macaques. We investigated whether results in
      transgenic mice can predict the stimulation of fetal hemoglobin in primates, by
      testing gamma globin induction in response to a new ribonucleotide reductase
      inhibitor, Didox. A transgenic mouse line carrying the human A gamma gene linked
      to a locus control region cassette was used. Treatment of transgenic mice with
      Didox resulted in induction of gamma gene expression as documented by an increase
      in F reticulocytes and F cells and an elevation of gamma/gamma + beta
      biosynthetic ratio. Similarly, administration of Didox to a baboon in the
      nonanemic and chronically anemic state resulted in induction of gamma gene
      expression as shown by increases in F reticulocytes, F cells, and Hb F. These
      results suggest that the muLCR-A gamma transgenic mice can be used to screen new
      pharmacologic compounds for gamma globin inducibility.

PMID- 7511331
TI  - CD21 antigen in T-lineage neoplastic lymphoid cells: characteristic expression at
      thymic stage.
AB  - The expression of CD21 antigen, a receptor for the C3d fragment of complement and
      Epstein-Barr virus (EBV), was investigated in a total of 85 cases of neoplastic
      lymphoid cells including 39 cases of T-lineage acute lymphoblastic leukemia
      (ALL)/lymphoblastic lymphoma (LBL), although CD21 antigen is usually regarded as
      a pan-B antigen. The CD21 antigen was expressed by one of the eight cases of
      neoplastic lymphoid cells expressing the CD7 antigen as a sole pan-T antigen, by
      three of the 20 cases of pro- or early thymic stage (CD7+ CD5+ CD2-, CD7+ CD5-
      CD2+, or CD7+ CD5+ CD2+, and ten of 11 cases of thymic stage (CD3+/- CD4+ CD8+),
      but not by one case of late thymic stage (CD3+ CD4+ CD8-) T-ALL/LBL cells. The
      CD21 antigen was not expressed by any of the 11 cases of adult T-cell leukemia
      (ATL) or two cases of chronic T-lineage leukemia. At most 4% of the normal
      thymocytes obtained from seven infants or children expressed the CD21 antigen.
      While only a very limited population of normal thymocytes expresses CD21 antigen,
      T-ALL/LBL cells at the thymic stage characteristically express CD21 antigen in
      contrast to pro- or early thymic ALL/LBL or peripheral-stage neoplastic T cells.
      The estimation of the expression of CD21 antigen is useful for delineating stages
      of differentiation in T-ALL/LBL. Furthermore, these observation are notable,
      considering the possibility that the reported EBV-carrying T-cell lymphomas
      result from the penetration of EBV into EBV-negative neoplastic T cells.

PMID- 7511332
TI  - Expression of the thrombospondin receptor (CD36) on the cell surface in
      megakaryoblastic and promegakaryocytic leukemias: increment of the receptor by
      megakaryocyte differentiation in vitro.
AB  - In this report we describe four cases of acute megakaryocytic leukemia
      demonstrated by the presence of megakaryocyte-platelet-related cell-surface
      antigens. These were detected utilizing flow cytometry and monoclonal antibodies
      in addition to both platelet peroxidase activity, which was shown by
      ultrastractural cytochemistry, and emergence of differentiation antigens, while
      culturing these leukemic cells. The blasts of one patient possessed both platelet
      GpIb and GpIIb/IIIa cell-surface antigens detected by AN51(CD42b), J15, P2, and
      HPL2(CD41), respectively, whereas the remaining three patients almost completely
      lacked GpIb cell-surface antigen. Hence the former were diagnosed as
      immature(pro)megakaryocytic leukemia and the latter as acute megakaryoblastic
      leukemia from the viewpoint of immunophenotypic analysis. While we cultured these
      leukemic cells in conditioned medium prepared from phytohemagglutinin-stimulated
      leukocytes and interleukin 3, expression of CD36(OKM5) antigen (thrombospondin
      receptor) increased gradually according to the differentiation and maturation of
      these cells. Finally, all leukemic cells differentiated to mature megakaryocytes.
      The function of CD36 on these cells remains to be elucidated.

PMID- 7511334
TI  - Palliative fetal surgery for diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia is associated with a poor prognosis in spite of
      advances in antenatal detection and newborn care. Open fetal surgery has been
      suggested as a strategy for salvaging selected fetuses at high risk for pulmonary
      hypoplasia as a result of this lesion. We report a strategy for palliative fetal
      surgery with definitive repair postponed to the newborn period.

PMID- 7511333
TI  - Fibroblast growth factor regulates insulin-like growth factor-binding protein
      production by vascular smooth muscle cells.
AB  - Insulin-like growth factor I is an important mitogen for vascular smooth muscle
      cells, and its effects are regulated by several binding proteins. Western ligand
      blotting of conditioned medium from rat aortic smooth muscle cells detected a 24
      kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent
      with insulin-like growth factor binding protein-4 by size. Low amounts of a
      glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31
      kDa non-glycosylated protein also were present. Basic fibroblast growth factor
      markedly increased secretion of the 24 kDa binding protein and its 28 kDa
      glycosylated variant. This effect was dose- and time-dependent and was inhibited
      by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth
      factor I to cell monolayers revealed no surface-associated binding proteins,
      either basally or after agonist treatment. Induction of binding protein
      production by fibroblast growth factor at sites of vascular injury may be
      important in vascular proliferative responses in vivo.

PMID- 7511335
TI  - Maternal serum screening for Down syndrome before 15 weeks.

PMID- 7511336
TI  - Heterologous expression of delta F508 CFTR results in decreased sialylation of
      membrane glycoconjugates.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is commonly
      mutated in cystic fibrosis to the delta F508 CFTR. CFTR has been shown to
      function as a adenosine 3',5'-cyclic monophosphate-dependent Cl- channel at the
      cell surface, and there is evidence to suggest that CFTR may also have a role in
      transmembrane Cl- conductance in intracellular membrane compartments. Studies
      using cells from cystic fibrosis patients or heterologous expression systems have
      demonstrated that defective Cl- conductance at the cell surface and defective
      acidification of the Golgi compartment are associated with the presence of mutant
      forms of CFTR. It is possible that mutation of CFTR could also result in altered
      Golgi function, consistent with reports of changes in the glycosylation of cell
      surface and secreted glycoproteins in cystic fibrosis. Glycosylation of cell
      surface glycoproteins, particularly levels of sialylation, may also be related to
      the increased binding of Pseudomonas to cystic fibrosis cells. The current study
      was undertaken to compare the sialylation of cell surface glycoconjugates in
      heterologous cells overexpressing normal CFTR or delta F508 CFTR. The presence of
      sialylated residues on cells was assessed by the surface binding of the specific
      lectins, wheat germ agglutinin and elderberry bark lectin. A fluorescent cholera
      toxin B subunit probe was used to measure surface binding to sialylated
      gangliosides in transfected cells. Our studies show that cells lacking CFTR and
      cells expressing normal CFTR have unaltered levels of sialylation. In contrast,
      cells expressing the delta F508 CFTR have significantly decreased amounts of
      sialylated glycoproteins and gangliosides on the cell surface.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7511337
TI  - Enhanced Na(+)-H+ exchanger activity and NHE-1 mRNA levels in human lymphocytes
      during metabolic acidosis.
AB  - It has recently been demonstrated that uremic metabolic acidosis and experimental
      metabolic acidosis caused by ingestion of ammonium chloride coincide with
      increased Na(+)-H+ exchanger (NHE-1) activity in human blood cells. In the
      present study, we investigated whether an increased level of NHE-1 specific mRNA
      in human lymphocytes during the course of an experimental metabolic acidosis
      could explain the enhanced transport activity during metabolic acidosis. Six
      healthy individuals were studied before and after 5 days of taking 15 g of
      ammonium chloride daily. Plasma pH and bicarbonate decreased significantly, from
      7.42 +/- 0.027 to 7.28 +/- 0.05 and from 26.7 +/- 2.0 to 15.6 +/- 2.9 mM,
      respectively. Basal cytosolic pH (pHi) and Na(+)-H+ exchange activity were
      measured in lymphocytes loaded with the fluorescent pHi indicator 2',7'
      bis(carboxyethyl)-5(6)-carboxyfluorescein. Basal pHi remained unchanged during
      metabolic acidosis (7.03 +/- 0.07 vs. 7.03 +/- 0.06). Ethylisopropylamiloride
      sensitive pHi recovery increased from 0.046 +/- 0.007 to 0.076 +/- 0.012 dpHi/min
      (P < 0.0001). The transcript level of NHE-1 mRNA was measured by reverse
      transcription polymerase chain reaction in comparison with a constitutively
      expressed reference gene (glyceraldehyde-3-phosphate dehydrogenase). NHE-1 mRNA
      in human lymphocytes increased 1.5-fold in metabolic acidosis. These data suggest
      that the increased Na(+)-H+ exchange activity in metabolic acidosis may be caused
      by de novo synthesis of antiport protein.

PMID- 7511338
TI  - Voltage-dependent gap junctional conductance in hepatopancreatic cells of
      Procambarus clarkii.
AB  - Properties of gap junction channels present between specific cell types
      constituting the hepatopancreas of the crayfish (Procambarus clarkii) were
      investigated using the dual whole cell voltage clamp technique. Four different
      cell types (E, Fe, R and B) were identified on the basis of their morphology
      using light and electron microscopy. Although junctional conductance (Gj) could
      not be measured in B-B cell pairs, junctional currents were resolved in both
      homologous and heterologous combinations of the other cell types. E-E, Fe-Fe, and
      E-Fe cell pairs exhibited strong dependence on inside-out voltage (Vi-o), such
      that Gj increased with hyperpolarization to a maximal plateau reached at
      approximately -40 mV and was abolished with depolarization > 10 mV. The Gj-Vi-o
      relationship can be described by a squared Boltzmann relation with A = 0.101 and
      V0 = 0.135 mV. In this system, sensitivity of the junctions to transjunctional
      voltage was slight, if present at all. Gating mechanisms were complex, as
      evidence by the presence of multiple unitary channel conductance states. Single
      channel recordings showed that large unitary conductances (> 200 pS) were
      generally found between E-E, Fe-Fe, and E-Fe cell pairs, whereas smaller channel
      sizes (< 90 pS) were detected between R-R cell pairs.

PMID- 7511339
TI  - Increase in insulin-like growth factor I in hypertrophying smooth muscle.
AB  - The present study focuses on the role of the insulin-like growth factor (IGF)
      system in the development of smooth muscle hypertrophy. Hypertrophy was initiated
      by partial ligation of portal vein or urethra in female Sprague-Dawley rats
      weighing approximately 220 g. Levels of mRNA were analyzed by solution
      hybridization. Seven days after ligation, the wet weight of the portal vein was
      increased about threefold and the concentration of IGF-I mRNA was increased
      fourfold. The bladder wet weight was increased twofold 3 days after ligation and
      fourfold 10 days after ligation. IGF-I mRNA in the bladder was elevated 3-fold
      after 3 days and 2.5-fold after 10 days, whereas IGF binding protein 2 mRNA was
      increased approximately 2-fold after 3 days and 5-fold after 10 days. IGF-I
      receptor mRNA in the hypertrophying bladder remained unchanged. Increased levels
      of IGF-I were demonstrated with immunohistochemistry in both hypertrophying
      portal vein and urinary bladder. The results show a specific increase in IGF-I
      mRNA as well as an increased IGF-I immunoreactivity during hypertrophy of smooth
      muscle, which suggests that the local IGF-system may play a role in smooth muscle
      hypertrophy.

PMID- 7511341
TI  - Antiproliferative effect of prostaglandin E2 in cultured guinea pig tracheal
      smooth muscle cells.
AB  - The respiratory epithelium plays an important role in modulating airway smooth
      muscle responsiveness to contractile agonists, and damage of the epithelium may
      be involved in the pathogenesis of bronchial hyperresponsiveness. This study was
      undertaken to determine whether prostaglandin E2 (PGE2), a relaxant agent
      synthesized and released by airway epithelial cells, could exert long-term
      effects on airway smooth muscle by regulating cell proliferation. Incubation of
      growth-arrested tracheal smooth muscle cells with serum for 24 h stimulated DNA
      synthesis in a concentration-dependent manner, as determined by [3H]thymidine
      incorporation. PGE2 and forskolin, a direct activator of adenylate cyclase,
      inhibited serum-induced cell proliferation, and the effects were dose dependent.
      PGE2 and forskolin also stimulated adenosine 3',5'-cyclic monophosphate
      accumulation. An inhibitor of cyclooxygenase, indomethacin, enhanced DNA
      synthesis induced by serum. These results indicate that exogenous PGE2 exerts an
      antiproliferative effect on smooth muscle cells in culture by activation of
      adenylate cyclase and suggest a role for the epithelium in modulating airway
      smooth muscle growth.

PMID- 7511340
TI  - Multiple inhibitory effects of genistein on stimulus-secretion coupling in rat
      pancreatic acini.
AB  - Genistein, a tyrosine kinase inhibitor, inhibited cholecystokinin (CCK)-induced
      maximal amylase release from rat pancreatic acini by 18, 31, and 46% at
      concentrations of 100, 300, and 750 microM, respectively, after 30 min
      preincubation. Genistein similarly decreased amylase release stimulated by
      bombesin but not that stimulated by secretin or vasoactive intestinal peptide.
      The steps of stimulus-secretion coupling affected by genistein were further
      evaluated. We found genistein dose dependently suppressed CCK-as well as NaF
      induced polyphosphoinositide hydrolysis with a 50% inhibitory concentration of
      380 and 400 microM, respectively, but only slightly suppressed the increase of
      intracellular Ca2+ concentration in response to either low or high concentrations
      of CCK. Genistein at 300 microM also decreased incorporation of [3H]inositol into
      phosphatidylinositol 4,5-bisphosphate. Most strikingly, 300 microM genistein
      inhibited Ca(2+)-stimulated amylase release by 85% in streptolysin O
      permeabilized acini and thapsigargin-stimulated amylase release by 69% in intact
      acini. Daidzein, the inactive analogue of genistein, had no effect on any of the
      above parameters. Genistein, up to 750 microM, did not affect amylase release in
      response to phorbol ester. To relate these inhibitory effects of genistein to its
      inhibition of tyrosine phosphorylation, Western blotting was performed with an
      anti-phosphotyrosine monoclonal antibody. Genistein at 100 microM partly and at
      300 microM completely inhibited CCK-induced tyrosine phosphorylation. In
      conclusion, genistein inhibits amylase release at multiple stages of stimulus
      secretion coupling. These effects most likely involve both tyrosine kinase
      dependent and -independent mechanisms.

PMID- 7511343
TI  - Intracellular processing of immune complexes formed on the surface of glomerular
      epithelial cells.
AB  - Immune complexes formed on the surface of glomerular epithelial cells (GEC)
      resolve slowly and therefore result in inflammation of the glomerular capillary
      wall, as in the case of human membranous glomerulonephritis. The metabolic defect
      in the processing of these complexes has not been identified. Immune complexes of
      cationic bovine gamma-globulin (BGG) and anti-BGG were formed on cultured GEC,
      and their intracellular processing was followed by tracing the fate of
      radioiodinated and colloidal gold-labeled anti-BGG in the endosomal, lysosomal,
      and extracellular compartments. It was determined that the complexes were rapidly
      internalized in endosomes (50% saturation achieved in 10 min). The rate of
      expulsion of complexes was much slower (50% of internalized complex exteriorized
      in approximately 90 min). Of the internalized anti-BGG, < 5% were proteolytically
      degraded, suggesting an inefficient lysosomal processing. This aspect was studied
      further by separating anti-BGG colloidal gold-loaded vesicles by low-speed
      centrifugation and quantitating the lysosomal enzymes acid phosphatase and beta
      galactosidase. At equilibrium approximately 10% of total cellular enzymes was
      associated with the vesicles. It was concluded that immune complexes are rapidly
      internalized by the GEC. However, lysosomal processing of the complexes is slow
      and inefficient. The majority of accumulated endosomes route back to the plasma
      membrane and discharge their contents in the medium in the form of free antibody.

PMID- 7511342
TI  - Glutathione protects signal transduction in type II cells under oxidant stress.
AB  - Brief exposure of type II cells to 100 microM t-butyl hydroperoxide (tBOOH)
      inhibits agonist-induced surfactant secretion and second messenger generation
      presumably through the oxidation of membrane lipids. Since glutathione (GSH)
      reduces lipid peroxides and protects type II cells from oxidant injury as
      determined by crude indicators, then GSH should also protect signal transduction.
      In the current study, tBOOH inhibited ATP-induced adenosine 3',5'-cyclic
      monophosphate and inositol trisphosphate generation and surfactant secretion.
      Stimulation of surfactant secretion by forskolin or phorbol acetate was also
      inhibited by tBOOH. Pretreatment with GSH (1 mM) blocked the tBOOH inhibition.
      This protection occurred in the presence of gamma-glutamyl transferase and gamma
      glutamylcysteine synthetase inhibitors and suggested GSH was transported as an
      intact molecule. GSH protection was blocked by gamma-L-glutamyl-L-glutamate, an
      agent that blocks GSH transport. Protection of surfactant secretion and signal
      transduction was also provided by the constitutive amino acids but not if GSH
      synthesis was blocked. In the cultured type II cell model, GSH transport and
      synthesis protected signal transduction and, subsequently, surfactant secretion
      against oxidant injury.

PMID- 7511344
TI  - Effect of U-73,122, an inhibitor of phospholipase C, on actions of parathyroid
      hormone in opossum kidney cells.
AB  - The relative roles of the adenylate cyclase-protein kinase A system (AC-PKA), the
      phospholipase C-protein kinase C system (PLC-PKC), and increases in cytosolic
      calcium in mediating the final actions of parathyroid hormone (PTH) remain ill
      defined. Although an important role for the PLC-PKC system in the regulation of
      phosphate transport in response to PTH has been suggested, previous studies from
      our laboratory and others, in OK cells, have emphasized the major role of AC-PKA.
      The present studies were designed to dissociate the second messengers for PTH by
      using an inhibitor of PLC (U-73,122). Studies were performed in confluent
      cultures of OK cells with and without preincubation with U-73,122 (1 microM).
      This inhibitor did not alter adenosine 3',5'-cyclic monophosphate (cAMP)
      production or the activation of PKA in response to PTH. Preincubation with U
      73,122, however, totally abolished PTH-stimulated increases in diglyceride mass,
      consistent with inhibition of PLC. Activation of particulate PKC was then
      examined in response to PTH in the absence and presence of U-73,122. Although PTH
      resulted in an increase in particulate PKC activity in control cultures, this
      effect was abolished in the presence of U-73,122 and actually decreased
      significantly. Therefore, having documented marked attenuation of PLC-PKC, we
      next examined the effects of PTH on phosphate transport. Basal phosphate uptake
      was not altered by 1 microM U-73,122. Dose-response curves of the inhibition of
      phosphate transport in response to PTH were identical in the presence or absence
      of U-73,122. Thus inhibition of PLC and PKC activities did not alter the effects
      of PTH on phosphate transport.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511345
TI  - Prostacyclin is required for t-PA release after venous occlusion.
AB  - The role of vascular cyclooxygenase pathway on tissue-type plasminogen activator
      (t-PA) release after venous occlusion was studied in anesthetized rats. After the
      inferior vena cava was clamped for 30 min, fibrinolytic activity increased from
      143.7 +/- 14.5 to 209.5 +/- 10.3 mm2 (mean +/- SE, P < 0.002). This increase was
      prevented by aspirin at high (100 mg/kg i.v.) but not at low doses (1 mg/kg
      i.v.). Dazoxiben (10 mg/kg i.v.), an inhibitor of thromboxane synthase, was
      ineffective on the fibrinolytic response. Both the basal levels of 6
      ketoprostaglandin F1 alpha and its increase after venous occlusion were
      suppressed by 100 mg/kg aspirin administration (from 0.64 +/- 0.2 to 0.05 +/-
      0.002 ng/ml before occlusion, P < 0.001; and from 1.08 +/- 0.2 to 0.06 +/- 0.002
      ng/kg after occlusion, P < 0.001), whereas they were both unaffected by aspirin
      at low doses (from 0.53 +/- 0.06 before to 1.20 +/- 0.08 ng/ml after stasis).
      Moreover, iloprost, a stable analogue of prostacyclin, reversed the aspirin
      inhibitory effects on fibrinolytic activity by restoring t-PA vascular release
      after venous stasis. Our results provide experimental evidence that an intact
      cyclooxygenase pathway in vascular wall is required for the fibrinolytic activity
      increase after venous occlusion in rats.

PMID- 7511348
TI  - Heterogeneous populations of K+ channels mediate EDRF release to flow but not
      agonists in rabbit aorta.
AB  - We have investigated the role of Ca(2+)- and ATP-sensitive K+ channels (KCa and
      KATP, respectively) in flow- and agonist-stimulated release of endothelium
      derived relaxing factor (EDRF). Segments of rabbit abdominal aorta, perfused at
      constant flow with buffer containing indomethacin, were used as a source of EDRF
      in cascade bioassay, and responses to endothelium-dependent agonists were studied
      isometrically in rings of the same tissue in the absence of flow. Apamin,
      charybdotoxin (ChTX), and tetraethylammonium (TEA) were used to block a variety
      of low, medium, and high conductance KCa channels, and glibenclamide was used to
      block KATP channels. The effects of flow pulsatility were studied at pulse
      frequencies ranging from 0.15 to 9.75 Hz, and time-averaged shear stress was
      manipulated by adding dextran (80,000 mol wt) to the perfusate to increase its
      viscosity. Frequency-related EDRF release was maximal at approximately 5 Hz and
      attenuated by apamin, TEA, and ChTX, but not by glibenclamide. EDRF release
      stimulated by increased viscosity was attenuated by TEA, ChTX, and glibenclamide,
      but not by apamin. In marked contrast, EDRF release stimulated by acetylcholine
      and ATP was unaffected by blockade of either KCa or KATP channels. We conclude
      that a spectrum of KCa channel subtypes mediates endothelial transduction of the
      oscillatory component of pulsatile flow and that KATP channels may be
      additionally involved in the transduction of time-averaged shear stress. In
      contrast, agonist-stimulated endothelium-dependent relaxation is independent of
      K+ channel activation in rabbit aorta.

PMID- 7511347
TI  - Hypoxia, alpha 2-adrenergic, and nitric oxide-dependent interactions on canine
      cerebral blood flow.
AB  - We tested the hypothesis that NO synthase inhibition with N omega-nitro-L
      arginine methyl ester (L-NAME) and alpha 2-adrenoreceptor stimulation with
      dexmedetomidine (Dex) decreases the cerebral blood flow (CBF) response to
      hypoxia. In isoflurane-anesthetized dogs, CBF was measured during two episodes of
      hypoxic hypoxia. In a control group (n = 6), CBF increased similarly from 83 +/-
      4 to 210 +/- 30 ml.min-1 x 100 g-1 and from 88 +/- 7 to 205 +/- 27 (+/- SE)
      ml.min-1 x 100 g-1 during two hypoxic episodes. In a second group (n = 6),
      hypoxia increased CBF from 88 +/- 15 to 204 +/- 38 ml.min-1 x 100 g-1. Dex (10
      micrograms/kg i.v.) reduced normoxic CBF to 54 +/- 8 ml.min-1 x 100 g-1, and
      subsequent hypoxia increased CBF to 97 +/- 14 ml.min-1 x 100 g-1. In a third
      group pretreated with L-NAME (40 mg/kg i.v.) 1 h before anesthesia (n = 6),
      normoxic CBF was less than in the control group (52 +/- 2 vs. 83 +/- 4 ml.min-1 x
      100 g-1). Hypoxia increased CBF to 177 +/- 13 ml.min-1 x 100 g-1. Dex after L
      NAME further decreased normoxic CBF to 37 +/- 3 ml.min-1 x 100 g-1, and
      subsequent hypoxia increased CBF to 106 +/- 18 ml.min-1 x 100 g-1. Dex, L-NAME,
      and Dex + L-NAME each reduced cerebral O2 transport (CBF x arterial O2 content)
      during normoxia, but the increase in CBF during hypoxia was sufficient to prevent
      further decreases in O2 transport. Thus the response to hypoxia remained
      proportional to normoxic levels of CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511346
TI  - Mechanisms of myogenic enhancement by norepinephrine.
AB  - Mechanisms contributing to the ability of norepinephrine (NE) to enhance
      arteriolar myogenic responsiveness were studied in the rat cremaster muscle.
      Anesthetized rats were enclosed in an airtight box that could be pressurized to
      increase intravascular pressure in the cremaster, which was exteriorized into a
      tissue bath. Vessel diameter, intravascular pressure, and red cell velocity were
      measured in the first-order (1A) arteriole during box pressure increases of 10,
      20, and 30 mmHg. Control arterioles [diameter = 113 +/- 3 (SE) microns] did not
      exhibit myogenic constriction in response to step increases in intravascular
      pressure (e.g., + 30 mmHg, diameter = 122 +/- 5 microns), whereas after 25%
      constriction with NE (diameter = 85 +/- 2 microns) arterioles exhibited
      significant myogenic constriction (e.g., +30 mmHg, diameter = 70 +/- 4 microns).
      The NE effect on myogenic reactivity was augmented by Ca2+ channel agonists and
      inhibited by antagonists, suggesting a role for voltage-operated Ca2+ channels.
      In contrast to NE, exposure to KCl (30 mM) did not enhance myogenic
      responsiveness, suggesting that factors in addition to voltage-operated channels
      were involved in the NE effect. The protein kinase C (PKC) activator indolactam
      (1 microM) was found to increase vascular tone in the 1A arterioles (diameter =
      109 +/- 6 to 89 +/- 7 microns) and to induce significant myogenic responsiveness
      similar to that produced by NE (e.g., +30 mmHg, diameter = 65 +/- 9 microns).
      Staurosporine (0.1 microM) and calphostin C (1 microM), inhibitors of PKC,
      significantly attenuated the NE-induced myogenic response.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7511349
TI  - Light/dye microvascular injury selectively eliminates hypercapnia-induced pial
      arteriolar dilation in newborn pigs.
AB  - Cerebral vasodilation in response to hypercapnia involves prostanoids in newborn
      pigs. This study examines the hypothesis that endothelial injury in vivo inhibits
      cerebral vasodilation and prostacyclin synthesis in response to hypercapnia, thus
      suggesting prostacyclin is a primary endothelium-derived vasodilating factor in
      newborn pig cerebral circulation. Anesthetized piglets with closed cranial
      windows were studied before and after injury caused by light/dye or before and
      after dye-only sham control. Light/dye injury was produced by injecting sodium
      fluorescein intravenously and passing filtered light from a mercury arc lamp
      through the cranial window. Ultrastructural changes to endothelium of pial
      vessels were produced that were characterized by surface pits, vacuolar
      cytoplasmic inclusions, and mitochondrial injury. After the light/dye injury,
      dilation to hypercapnia was absent while dilations to iloprost, isoproterenol,
      and sodium nitroprusside and constrictions to norepinephrine and acetylcholine
      were retained. Before light/dye treatment, hypercapnia increased cortical
      periarachnoid 6-keto prostaglandin F1 alpha concentration approximately
      threefold. However, after treatment, 6-keto-prostaglandin F1 alpha was not
      increased significantly in response to hypercapnia. These findings are consistent
      with the hypothesis that endothelial prostacyclin synthesis induced by
      hypercapnia participates in dilation of adjacent smooth muscle.

PMID- 7511350
TI  - Effect of inhibition of nitric oxide synthesis on vasopressin secretion in
      conscious rabbits.
AB  - NO synthase is present in magnocellular neurons of supraoptic and paraventricular
      nuclei as well as in the posterior pituitary gland and may participate in control
      of vasopressin secretion. To test this possibility, experiments were performed in
      conscious, chronically prepared rabbits to determine the effect of NO synthesis
      inhibition with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) on basal
      vasopressin secretion and vasopressin responses to increased plasma osmolality
      (hypertonic saline infusion; P osm) and decreased blood pressure (nitroprusside
      infusion). L-NAME infusion (0.5 mg.kg-1 x min-1 i.v.) increased mean arterial
      pressure [MAP; 82.6 +/- 3.4 to 93.0 +/- 3.0 mmHg (P < 0.02)], decreased heart
      rate [HR; 242 +/- 12 to 209 +/- 9 beats/min (P < 0.02)], decreased plasma renin
      activity [PRA; 3.1 +/- 0.6 to 2.0 +/- 0.6 ng.ml-.2 h-1 (P < 0.001)], and
      increased plasma vasopressin concentration [P AVP; 2.2 +/- 0.3 to 4.5 +/- 1.0
      pg/ml (P < 0.05)]. P(osm) did not change. Hypertonic saline infusion did not
      change MAP or HR but decreased PRA [4.3 +/- 0.8 to 0.9 +/- 0.2 ng.ml-1 x 2 h-1 (P
      < 0.01)], increased P(osm) [284 +/- 1 to 305 +/- 2 mosmol/kg H2O (P < 0.001)],
      and increased PAVP [2.8 +/- 0.3 to 12.7 +/- 2.7 pg/ml (P < 0.01)].(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7511351
TI  - Whole body and splanchnic leucine, phenylalanine, and glucose kinetics during
      endotoxemia in humans.
AB  - To examine the whole body and splanchnic tissue substrate handling during
      endotoxemia, an intravenous bolus of endotoxin was given to six healthy
      volunteers during primed, continuous infusions of [1-13C]leucine, [ring
      2H5]phenylalanine, and [6,6-2H2]glucose. Whole body protein breakdown, based on
      whole body Leu and Phe appearance rates (Ra), increased in response to endotoxin
      given at time 0 (RaLeu 77 +/- 2 mol.kg-1 x h-1, t = 0 h; 88 +/- 6, t = 4 h; P <
      0.05) (RaPhe 39 +/- 2 mol.kg-1 x h-1, t = 0; 46 +/- 3, t = 4 h; P < 0.05).
      Splanchnic amino acid balance (Bal) increased (BalLeu 7 +/- 4 mol.kg-1 x h-1, t =
      0; 21 +/- 5, t = 2 h; P < 0.05) (BalPhe 3 +/- 2 mol.kg-1 x h-1, t = 0; 16 +/- 4,
      t = 2 h; P < 0.05) and can be accounted for by increased splanchnic uptake (Rd)
      of Phe and Leu (RdLeu 21 +/- 3 mol.kg-1 x h -1, t = 0; 37 +/- 7, t = 120 min; P <
      0.05) (RdPhe 10 +/- 3 mol.kg-1 x h-1, t = 0; 24 +/- 5, t = 120 min; P < 0.05).
      Splanchnic conversion of Leu to ketoisocaproate increased with endotoxin
      administration (0.7 +/- 0.6 mol.kg-1 x h-1, t = 0; 8 +/- 3, t = 360 min; P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511352
TI  - Nitric oxide-dependent and -independent components of cerebrovasodilation
      elicited by hypercapnia.
AB  - We studied the effect of nitro-L-arginine methyl ester (L-NAME), a nitric oxide
      synthase (NOS) inhibitor, on the increases in cerebral blood flow (CBF) elicited
      by stepwise elevations in arterial partial pressure of CO2 (PaCO2) from
      normocapnia up to 204 mmHg. Rats were anesthetized with halothane and ventilated.
      CBF was monitored over the parietal cortex using a laser-Doppler flowmeter.
      Increasing levels of hypercapnia elicited graded elevations in CBF that reached a
      plateau at PaCO2 = 82 +/- 1 mmHg (CBF +215 +/- 25%; n = 8; P < 0.05, analysis of
      variance). L-NAME (40 mg/kg i.v.; n = 8), but not nitro-D-arginine methyl ester
      (n = 8), reduced resting CBF (-42 +/- 4%) and attenuated the increase in CBF
      elicited by hypercapnia. The attenuation occurred only at PaCO2 40-80 mmHg and
      was maximal (-75 +/- 8%; P < 0.05) at 54 +/- 2 mmHg. At PaCO2 > or = 100 mmHg, L
      NAME (40-80 mg/kg) did not attenuate the response (P > 0.05). Reduction of
      resting CBF (-50 +/- 4%; n = 6) by administration of chloralose (20-40 mg/kg
      i.v.) did not attenuate the CBF response to hypercapnia (P > 0.05). We also found
      that the attenuation by L-NAME of resting CBF (n = 5) and of the
      cerebrovasodilation elicited by hypercapnia (n = 6) has a relatively slow time
      course, the effects reaching a maximum 45-60 min after intravenous administration
      of the drug. We conclude that L-NAME does not attenuate the CBF response to CO2
      uniformly at all levels of hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511353
TI  - Localized malignant mesothelioma. A clinicopathologic and flow cytometric study.
AB  - Six examples of malignant mesothelioma appearing as a localized pleural mass are
      described. There were four women and two men, ranging in age from 42 to 76 years.
      A history of asbestos exposure was obtained from three patients. The tumors
      ranged in size from 2.8 to 10 cm. Two were pedunculated and four were sessile
      with broad-based pleural attachments. Histologically, three tumors were purely
      epithelioid and three were biphasic. Immunohistochemical stains in all six cases
      were positive for cytokeratin and negative for carcinoembryonic antigen. Five
      were also positive for epithelial membrane antigen. Five were negative for Leu
      M1, while one showed focal staining in a peripheral membrane pattern. Electron
      microscopy in two purely epithelioid tumors showed long, thin microvilli, well
      developed desmosomes, and numerous tonofilaments. Flow cytometry showed an
      aneuploid DNA content in four tumors and a diploid content in one. Flow cytometry
      in five cases identified a DNA aneuploid cell population in four tumors and a
      diploid population in one. Three patients showed signs of local recurrences 4, 7,
      and 18 months after excision and died of their disease 12, 10, and 24 months
      after diagnosis, respectively. Three patients are well with no evidence of
      disease 8, 24, and 96 months after diagnosis. These findings indicate that
      malignant mesotheliomas of the pleura may rarely appear as a localized mass. The
      biologic behavior of such tumors is difficult to predict, but some patients
      survive disease-free for a long time after surgical excision.

PMID- 7511354
TI  - Small-cell carcinoma of the endometrium. A clinicopathological study of sixteen
      cases.
AB  - Sixteen cases of small-cell carcinoma of the endometrium were encountered in
      patients who ranged in age from 30 to 78 (mean, 57.4) years. Of the 12 patients
      whose presenting features are known, eight had abnormal vaginal bleeding, three
      had pain related to metastatic tumor, and one patient had both symptoms. On
      pelvic examination, adnexal masses were palpable in three patients, and vaginal
      involvement was evident in two; one patient had a large palpable periumbilical
      mass. Thirteen patients underwent total abdominal hysterectomy and bilateral
      salpingo-oophorectomy. Extrauterine spread was documented intraoperatively in
      eight cases, including widespread intraabdominal and ovarian metastases in four
      cases, vaginal involvement in the two cases noted previously, paraaortic lymph
      node involvement in one case, and tubal involvement in one case. Three tumors
      were International Federation of Gynecology and Obstetrics (FIGO) stage I, four
      were stage II, two were stage III, and six were stage IV; in one case, there was
      insufficient information to allow staging. On gross examination, the tumors were
      usually described as bulky, ill-defined, and invasive of the myometrium; four
      were polypoid. Microscopic examination revealed sheets, cords, and nests of small
      or intermediate-sized cells with scanty cytoplasm, hyperchromatic nuclei, and a
      high mitotic rate. Single-cell and zonal necrosis and vascular invasion were
      typically present. Synchronous grade 1 or grade 2 endometrial endometrioid
      adenocarcinoma was present in eight cases, and complex atypical endometrial
      hyperplasia, in two others. In three cases, the adenocarcinoma merged almost
      imperceptibly with the small-cell component. None of the tumors contained
      argyrophil or argentaffin cells, although nine of 11 tumors were immunoreactive
      for neuron-specific enolase (one of these was also Leu-7 positive), and another
      was chromogranin positive. Of the 11 cases with follow-up information, seven
      patients died of disease (at least four with distant metastases) with a median
      survival of 12 months, and another patient was alive with distant metastases at
      18 months. The remaining patients were clinically free of disease at
      postoperative intervals of < or = 1 year (two cases) and 4.5 years (one case).
      This study confirms that small-cell carcinomas of the endometrium are a
      histologically distinctive subtype of endometrial carcinoma, which, like their
      counterparts in the uterine cervix, are aggressive tumors with a propensity for
      systemic spread and a poor prognosis.

PMID- 7511355
TI  - Detection of Epstein-Barr viral RNA in sinonasal undifferentiated carcinoma from
      Western and Asian patients.
AB  - Undifferentiated carcinoma of the nasopharynx has a well-known association with
      Epstein-Barr virus (EBV), but only an inconsistent relationship has been
      identified in undifferentiated carcinomas occurring at other sites. We
      investigated 22 formalin-fixed, paraffin-embedded cases of sinonasal
      undifferentiated carcinomas (SNUCs) occurring in Western and Asian patients. A
      highly sensitive in situ hybridization method was performed using an antisense
      oligonucleotide probe to the EBER1 gene of EBV. We identified EBV RNA in seven of
      11 SNUCs from Asian patients, but in none of the Western SNUC patients (0/11).
      The EBER1 signal was present in all or virtually all of the tumor cell nuclei in
      the seven EBV-RNA-positive Asian SNUCs. The latent membrane protein-1 (LMP1) of
      EBV was not identified in any of the five positive cases tested. Our results
      suggest that genetic predisposition or environmental/geographical cofactors play
      an important role in determining the strength of the association of SNUC with
      EBV.

PMID- 7511356
TI  - Epithelial-myoepithelial tumor of the bronchus.
AB  - A primary bronchial tumor with a histological pattern similar to that of
      epithelial-myoepithelial tumor of the salivary gland is reported in a 55-year-old
      woman. The tumor was well delimited, although not encapsulated, and showed a
      polypoid growth. The tumor was composed of two types of neoplastic cells:
      epithelial cells displaying tubules and myoepithelial cells that either formed
      compact masses or surrounded the tubular formations. Immunohistochemical study
      confirmed positive immunoreaction to both high- and low-molecular-weight
      cytokeratins in the epithelial cells and positive immunoreaction to vimentin, S
      100 protein, and myosin in the myoepithelial cells.

PMID- 7511357
TI  - Humans anesthetized with sevoflurane or isoflurane have similar arrhythmic
      response to epinephrine.
AB  - BACKGROUND: Anesthetics can alter the dose of exogenously administered
      epinephrine that causes cardiac arrhythmias. The purpose of this study was to
      test the hypothesis that in humans anesthetized with sevoflurane, the arrhythmic
      response to epinephrine is not different from the response in humans anesthetized
      with isoflurane. METHODS: We determined the arrhythmogenicity of submucosally
      administered epinephrine in 40 ASA physical status 1 or 2 patients who were to
      undergo transsphenoidal surgery. Patients were assigned randomly to be given 1.0
      1.3 minimum alveolar concentration sevoflurane or isoflurane. A surgeon, blinded
      to the anesthetic and the concentration of epinephrine, injected into the nasal
      submucosa epinephrine 10, 13.3, or 20 micrograms/ml in saline of volume
      sufficient for surgical need. We defined a "positive" response as three or more
      premature ventricular contractions within 5 min after initiation of injection.
      Responses between anesthetic groups within each dose range of epinephrine were
      compared by chi-squared analysis. RESULTS: No patient given either anesthetic
      developed premature ventricular contractions with doses of epinephrine less than
      5 micrograms/kg. At larger doses of epinephrine (5-9.9 and 10-14.9
      micrograms/kg), the frequency of arrhythmias did not differ between patients
      given sevoflurane and patients given isoflurane. Patients anesthetized with 1.2
      minimum alveolar concentration sevoflurane had blood pressure similar to and
      heart rate less than those of patients anesthetized with similar concentrations
      of isoflurane. Blood pressure and heart rate were increased similarly in both
      groups after laryngoscopy and tracheal intubation and after epinephrine
      injection. CONCLUSIONS: Sevoflurane and isoflurane do not differ in their
      sensitization of the human myocardium to the arrhythmogenic effect of exogenously
      administered epinephrine.

PMID- 7511358
TI  - Secretagogue-induced [14C]aminopyrine uptake in isolated equine parietal cells.
AB  - Equine oxyntic mucosal cells were obtained by sequential exposure to pronase and
      collagenase. Acid production by parietal cells was assessed by uptake of
      [14C]aminopyrine (AP), a weak base that accumulates in intracellular acidic
      spaces. Incubation for various times revealed a maximal AP uptake at 10 minutes
      for histamine and carbachol. Similar secretagogue responses were observed for
      parietal cells from the mucosal cell preparation or after enrichment by
      elutriation. Histamine and isobutyl-methylxanthine (IBMX) stimulated AP uptake
      with a dose-dependent response and maximal effective concentration of 100 microM.
      Carbachol, 1 to 100 microM, and pentagastrin (PG), 1 to 1,000 nM, were
      ineffective stimulants of AP uptake. The AP uptake values for 100 microM IBMX, 1
      microM carbachol, or 100 nM PG were 77 +/- 6%, 50 +/- 3.2%, and 40 +/- 4.5%,
      respectively, of that observed with maximal stimulation by 100 microM histamine
      (mean +/- SEM, n = 4 to 14). Uptake of AP by nonstimulated control cells was 36
      +/- 3.6% of maximal histamine stimulation. The AP accumulations during control
      conditions and after stimulation with 100 microM histamine and IBMX, 1 microM
      carbachol, or 100 nM PG were 1.18 +/- 0.39, 2.81 +/- 0.85, 1.93 +/- 0.48, 1.44 +/
      0.36, and 1.23 +/- 0.33 pmol of AP/10(5) parietal cells, respectively.
      Individual histamine dose-response curves were shifted to the right by increasing
      ranitidine and cimetidine concentrations (0.1 to 50 microM). These results
      indicate that isolated equine parietal cells are maximally stimulated by
      histamine and minimally stimulated by carbachol and PG.

PMID- 7511359
TI  - Substance P immunohistochemical study of the sensory innervation of normal
      subchondral bone in the equine metacarpophalangeal joint.
AB  - Serial sections of bone and soft tissue from the metacarpophalangeal joints of 2
      mature and 2 immature horses were evaluated for substance P immunoreactive
      sensory nerve fibers. Formalin-fixed specimens were sectioned, either
      nondemineralized or demineralized with formic acid or EDTA. Rabbit antiserum to
      substance P (SP) was used in the streptavidin-biotin-peroxidase complex method
      for immunolocalization of SP antigen, and staining with 3,3'-diaminobenzidine was
      used for permanent identification of SP fibers. Abundant sensory nerve fibers
      were identified in the joint capsule, synovial membrane subintimal layers,
      collateral ligaments, suspensory ligament and distal sesamoidean ligament
      attachments to the sesamoid bones, and the periarticular periosteal layers.
      Sparse SP-immunoreactive nerve fibers were found in subchondral bone plates of
      the metacarpus, proximal first phalanx, and dorsal articular surface of the
      sesamoid bones. Most SP fibers were associated with blood vessels in the small
      cancellous spaces and haversian canals of the subchondral bone. The deeper marrow
      spaces contained increased numbers of SP sensory fibers; a few appeared in small
      groups and as several SP-immunoreactive fibers in a larger nerve. Cortical bone
      contained only a few SP fibers in the haversian canals. Substance P fibers were
      not identified in the osteocytic lacunae, canaliculi, or the bony lamellae of the
      haversian systems of the subchondral bone plate, and its extension to the
      metaphyseal and diaphyseal cortical bone. Equine metacarpophalangeal joint soft
      tissues have an abundant sensory nerve supply, similar to that of other
      species.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511360
TI  - Enzymatic assay for measurement of zidovudine triphosphate in peripheral blood
      mononuclear cells.
AB  - In this report, we describe a new method to measure intracellular zidovudine
      triphosphate (ZDV-TP) levels in peripheral blood mononuclear cells (PBMCs) from
      patients treated with ZDV by utilizing inhibition of human immunodeficiency virus
      type 1 reverse transcriptase activity by ZDV-TP. Intracellular levels of ZDV-TP
      were determined with our enzymatic assay in PBMCs isolated from the blood of
      healthy individuals incubated with different concentrations of labeled ZDV and
      were validated by high-performance liquid chromatography separation and liquid
      scintillation counting of the radioactive ZDV-TP. These methods gave virtually
      identical results over a range of ZDV-TP concentrations from 150 to 900 fmol. ZDV
      TP recoveries were over 90%, and the limit of quantitation of ZDV-TP by this
      method was 20 to 50 fmol. To demonstrate the utility of the method, plasma ZDV
      and intracellular ZDV-TP concentrations were measured at serial time points over
      6 h in 12 human immunodeficiency virus-infected volunteers following a single 100
      or 500-mg oral dose of ZDV. Systemic oral clearance rates were similar to those
      in previous studies with adults but were highly variable (range, 0.86 to 2.75
      liters/h/kg of body weight). The area under the plasma concentration versus time
      curve increased significantly (P < 0.0005) with the dose from a median value of
      1.2 mg.h/liter at the lower dose to 4.2 mg.h/liter at the higher dose. Median
      intracellular ZDV-TP levels ranged from 5 to 57 and 42 to 92 fmol/10(6) cells in
      volunteers administered 100 and 500 mg of ZDV, respectively. Intracellular ZDV-TP
      levels rose to a plateau value by 2 h and remained consistent to 6 h. Although
      the higher dose and higher areas under the curve yielded consistently higher
      intracellular ZDV-TP levels, systemic pharmacokinetics explains only a modest
      proportion of the variability in cellular pharmacokinetic. The ZDV-TP bioassay
      should prove useful in further studies of ZDV metabolism in patient-derived PBMCs
      at the doses of ZDV currently administered.

PMID- 7511361
TI  - Effects of antifungal therapy on inflammation, sterilization, and histology in
      experimental Candida albicans meningitis.
AB  - To assess the effects of antifungal therapy on the course of Candida albicans
      central nervous system infection and inflammation, we inoculated intracisternally
      10(5) CFU of C. albicans into rabbits. Fluconazole (10 mg/kg of body weight) or
      amphotericin B (1 mg/kg) was infused intravenously daily for 14 days. Treatment
      was initiated 24 h or 5 days after infection. Cerebrospinal fluid (CSF) was
      repeatedly obtained to culture the organisms, assess the level of inflammation,
      and measure drug concentrations. Brain tissue was obtained at the end of therapy
      for culture, drug concentration determinations, and histopathology. The median
      number of days of treatment required to sterilize CSF cultures was 4 days for
      fluconazole therapy and 1 day for amphotericin B therapy (P = 0.037). There was a
      significant reduction in tumor necrosis factor alpha and leukocyte concentrations
      in the CSF of animals treated early versus those in untreated control animals (P
      < 0.05 and P < 0.001, respectively; analysis of variance). Compared with treated
      animals, a higher proportion of cultured CSF samples from untreated animals were
      positive for Candida (P < 0.001). A cultured brain sample from 1 of the 12
      animals treated early with amphotericin B was positive for C. albicans (P < 0.01
      versus controls); cultures of brain samples from 3 of 12 animals treated early
      with fluconazole were positive, whereas cultures of brain samples from 10 of 12
      controls were positive (P < 0.05). The mean density of C. albicans was lower in
      the single culture-positive amphotericin B recipient (1 x 10(1) CFU/g of brain
      tissue) than in those treated with fluconazole (1 x 10(3) CFU/g) and in controls
      (8 x 10(4) CFU/g). In animals treated late, the density of C. albicans in the
      brain in relation to the number of days of therapy was significantly lower in
      amphotericin B recipients than in those treated with fluconazole (P < 0.01) and
      untreated controls (P < 0.01; analysis of covariance). By histopathology, a
      larger proportion of untreated animals compared with those treated early
      demonstrated features of severe infection such as perivasculitis, ventriculitis,
      and evidence of fungal organisms. Compared with amphotericin B-treated rabbits,
      those given fluconazole had a trend toward more severe pathologic lesions.
      Reduced susceptibility to both fluconazole and amphotericin B was observed in the
      C. albicans organisms isolated from the brain of one fluconazole-treated animal.
      These data suggest that amphotericin B is the preferred treatment for C. albicans
      infections of the central nervous system.

PMID- 7511362
TI  - Enhancement of natural killer activity and interferon induction by different
      acyclic nucleoside phosphonates.
AB  - Acyclic nucleoside phosphonate (ANP) analogues are a class of compounds with
      potent activity against herpesviruses and/or retroviruses. Our preliminary
      experiments have shown that 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a
      prototype of the ANP family, enhances some parameters of natural immunity. In
      this paper we have evaluated the effect of different schedules of administration
      of PMEA and other ANP analogues of clinical interest upon natural killer (NK)
      activity and interferon (IFN) production in a mouse model. The results show that
      PMEA significantly enhances NK activity and interferon production. Other ANP
      analogues tested in our system, i.e., 9-(2-phosphonylmethoxyethyl)-2,6
      diaminopurine (PMEDAP), and 9-(3-fluoro-2-phosphonylmethoxypropyl)adenine
      (FPMPA), similarly induced enhancement of natural immunity. The immunomodulating
      effect of PMEA was even more pronounced with a single administration compared to
      repeated administrations of the drug. Dose-dependent enhancement of NK activity
      and IFN production could also be demonstrated during chronic administration of
      PMEA (more resembling to what will be the schedule of administration of this drug
      in patients). Overall, the data here presented suggest that the enhancement of
      some natural immune functions induced by ANP analogues may add to the direct
      antiviral activity of these drugs against retroviruses and herpesviruses, and
      thus may be able to increase the host resistance against viral infections.

PMID- 7511364
TI  - Ultrastructural and immunohistochemical characterization of basal cells in three
      dimensional culture models of the skin.
AB  - Keratinocytes were cultured on fibroblast-free dermal substitutes made of type I
      collagen film (collagen dermal substitute) and an extracellular matrix gel film
      (matrix dermal substitute), each of which was laid on a lyophilized type I
      collagen sponge. The morphology of the basal keratinocytes in these three
      dimensional culture models of the skin was studied ultrastructurally and
      immunohistochemically to assess their differentiation to basal cells. The basal
      keratinocytes in the artificial epidermis cultured on the collagen dermal
      substitute showed poorly organized tonofibril networks and desmosomes. Neither
      the tonofibril-hemidesmosome complex nor the lamina densa were detected along the
      interface, where many cytoplasmic projections of basal keratinocytes were noted.
      There were no detectable antigens of type IV or VII collagen, LDA-1, or laminin
      in the interface. Bullous pemphigoid (BP) and 1-2B7B antigens and integrins were
      expressed along the cytoplasmic membrane and the projections of the basal
      keratinocytes. A high molecular weight keratin (keratin 1, 68 kDa, 34 beta B4)
      was detected only in part of the uppermost layers of this artificial epidermis.
      In contrast, basal keratinocytes in the artificial epidermis on the matrix dermal
      substitute developed tonofibril networks radiating to desmosomes and
      hemidesmosomes, under which a primitive lamina densa was present. Basement
      membrane zone antigens, such as type IV and VII collagens, LDA-1 and laminin were
      noted along the interface as were 1-2B7B and BP antigens and integrins. Laminin
      and type VII collagen were also detected along or in the membrane of the
      endoplasmic reticulum of basal keratinocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511365
TI  - [Ultrasound-guided transrectal biopsy of the prostate].

PMID- 7511363
TI  - Hyaluronan and CD44 in psoriatic skin. Intense staining for hyaluronan on dermal
      capillary loops and reduced expression of CD44 and hyaluronan in keratinocyte
      leukocyte interfaces.
AB  - The distributions of hyaluronan (HA) and its presumptive receptor, CD44, were
      studied in skin samples from 13 psoriasis vulgaris patients, using an HA-specific
      probe (HABC), and monoclonal antibodies, respectively. The general distribution
      of HA and CD44 in psoriatic lesional epidermis resembled that in normal
      epidermis. However, areas of epidermis invaded by leukocytes showed a local
      depletion of HA and CD44, particularly at the contact areas of keratinocytes to
      lymphocytes and neutrophils. Removal by cellular uptake or extracellular
      degradation of CD44 and HA may be required for tight adherence between a
      keratinocyte and a leukocyte. On the dermal side, the tips of the prolonged
      dermal papillae in psoriatic lesions were intensively stained with HABC. The
      dilated capillaries and the space below the tip basal lamina, in particular, were
      heavily covered with HA. Occasionally, a similar intense staining was seen around
      an enlarged capillary in uninvolved psoriatic skin. CD44-positive leukocytes were
      found around the affected capillaries. The accumulation of HA in the dermal
      papillae may support the growth of psoriatic lesions, since HA stimulates the
      growth of capillaries as well as attracting inflammatory cells.

PMID- 7511366
TI  - [Determination of prognostic factors in incidental prostatic carcinoma].
AB  - Over a ten year period, 5,954 patients with benign prostatic hyperplasia (BPH)
      were hospitalized in our Institution. Of these, 1,000 cases were randomly chosen
      for the present study. Surgery was performed in 930 patients: transurethral
      resection (TUR) in 665 (72%) and open prostatectomy in 265 (28%). The
      pathological analyses revealed prostatic adenocarcinoma in 36 patients (4%).
      Seven patients were excluded: 5 due to a short follow-up (less than one year),
      one who had died from pulmonary embolism immediately postoperatively and one who
      had developed metastatic disease a few months after the operation. The age of the
      29 evaluable patients ranged from 53 to 91 years (mean 72.7 years) and the
      overall mean follow-up was 43 months. Eighteen patients staged A1 were treated
      conservatively and followed from 12 to 127 months (mean 53.5 months). Two
      patients (11%) showed progression, one locally at 42 months (5.5%) and one
      developed bone metastasis at 15 months (5.5%) and died at 27 months (Mortality:
      5.5%). Of the eleven patients with stage A2 prostatic cancer, 7 were managed
      conservatively (watchful waiting), 1 underwent radical prostatectomy and 3
      received early hormone therapy for undifferentiated lesions. Five patients
      progressed (45%), including the three patients treated with early hormone
      therapy, 3 local (27%) and 2 systemic (18%). Two of the 11 patients died from
      cancer (18%) and 2 from unrelated causes. The Gleason grading system and tumor
      volume (focal or diffuse) were compared as prognostic factors using the Kaplan
      Meyer and log-rank test.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511367
TI  - [The usefulness of micturition flow acceleration in the diagnosis of bladder
      instability].
AB  - The acceleration of flow rate (ml/sg2) is a urodynamic parameter derived from
      free flow uroflowmetry. The present study was conducted to determine the role of
      this new parameter as an alternative to the standard filling cystometry in the
      diagnosis of detrusor instability in nocturnal enuresis, prostatism and female
      urinary incontinence. We have observed that it is not a useful parameter due to
      the large overlapping of the patients with unstable and normal bladder. For this
      reason it is not possible to establish significant predictive values.

PMID- 7511370
TI  - Morphological and molecular characterization of Frankia sp. isolates from nodules
      of Alnus nepalensis Don.
AB  - Nodules collected from Alnus nepalensis growing in mixed forest stands at three
      different sites around Shillong, were crushed in various culture media to obtain
      isolates of Frankia. The isolates were found to have typical Frankia morphology
      as revealed by the scanning electron microscope. Seedlings inoculated with
      isolates or crushed nodules formed nitrogen fixing nodules. Frankia specific DNA
      probes amplified the DNA of the tested isolate AnpUS4. Partial nucleotide
      sequence of the 16S rRNA gene indicated that AnpUS4 was phylogenetically distinct
      from all other Frankia strains characterized so far.

PMID- 7511368
TI  - The regulation of ribosomal RNA synthesis and bacterial cell growth.

PMID- 7511369
TI  - Incorporation of specific wall proteins during yeast and mycelial protoplast
      regeneration in Candida albicans.
AB  - The kinectics of incorporation of two precursor mannoproteins into the
      regenerating cell wall of Candida albicans protoplasts have been followed at 28
      degrees C and 37 degrees C using two monoclonal antibodies specific for protein
      epitopes (MAb 1B12 and 4C12) as probes. Both molecules were secreted from the
      beginning of the regeneration process, and their incorporation was retarded
      significantly. Analysis of the secreted materials by Western immunoblotting with
      MAb 1B12 allowed the identification of two closely migrating bands at apparent Mr
      higher than 170 kDa and significant amounts of a highly polydisperse material of
      even greater molecular mass. Some of these mannoproteinaceous species carried
      both N- and O-glycosidically linked mannose residues, as deduced from their drop
      in apparent Mr when synthesized in the presence of tunicamycin and by their
      reactivity with Concanavalin A. Following secretion, the molecules reacting with
      MAb 1B12 were incorporated into the regenerating walls by covalent binding. Then,
      when the antigen molecules were solubilized from partially regenerated walls,
      their mobility differed when regeneration took place at 28 degrees C
      (blastoconidia) or 37 degrees C (mycelial cells).

PMID- 7511371
TI  - Isolation and characterisation of porin from the outer membrane of Synechococcus
      PCC 6301.
AB  - Pore-forming protein (porin) was isolated from N,N-dimethyl-dodecylaminoxid
      (LDAO)-extracted outer membranes of Synechococcus PCC 6301 and purified by ion
      exchange chromatography on DEAE-Sephacel column. The apparent molecular mass on
      SDS-PAGE was determined to be about 52,000. The native porin was reconstituted
      into black lipid bilayer membranes and showed a single-channel conductance of 5.5
      nS in 1 M KCl. The porin was found to be N-terminally blocked. The C-terminal
      amino acid sequence was identified as Phe-Thr-Phe. Amino acid analysis suggested
      that the porin protein consists of about 420 amino acid residues, yielding a
      polarity of 43.6% and a molecular mass of 45,000 in contrast to the mobility on
      SDS-PAGE.

PMID- 7511372
TI  - In situ localization of tenascin mRNA in developing mouse teeth.
AB  - Tenascin is a large extracellular-matrix glycoprotein found in developing
      connective tissue. A cDNA probe to mouse tenascin, mTN2, was used to determine
      the cellular origins of this molecule in the murine tooth germ by in situ
      hybridization. At embryonic day 19, a hybridization signal significantly greater
      than background was detected with mTN2 in the subodontoblastic layer of the
      dental mesenchyme and in the inner enamel epithelium of the enamel organ. At
      postnatal day 1, a signal was detected over pre-odontoblasts and the strata
      intermedium and externum. No tenascin mRNA was detected in odontoblasts or the
      stellate reticulum at either age, and hybridization in ameloblasts was not
      significantly greater than background at postnatal day 1. Thus, much of the
      tenascin found throughout developing teeth appears to be synthesized by pre
      odontoblasts and the inner enamel epithelium, the two populations of cells
      destined to generate mineralized matrix.

PMID- 7511373
TI  - Adult congenital heart disease: principles and management guidelines: Part II.
AB  - The treatment of congenital heart disease may be palliative because many residua
      and sequelae persist into adulthood. Except for trivial lesions and anomalies
      such as PDA or secundum ASD where surgical cure is possible, continued
      supervision is mandatory. These patients deserve expert medical assessment from
      adult cardiologists and from other specialists when appropriate. The prevalence
      of postoperative adult congenital heart disease is increasing: by the year 2000
      it is estimated that over 2000 in each million of the adult population will have
      congenital heart disease, one third of these having undergone cardiac surgery. It
      is important that some adult cardiologists in each major centre develop skills in
      adult congenital heart disease for this new patient population.

PMID- 7511376
TI  - Convergence and divergence in the evolution of transport proteins.
AB  - Different families of transport proteins catalyze transmembrane solute
      translocation, employing different mechanisms and energy sources. Several of
      these functionally dissimilar proteins nevertheless exhibit similar structural
      units, consisting of six tightly packed alpha-helices which may comprise all or
      part of a transmembrane channel. It is now recognized that some of these families
      arose independently of each other by convergence, while others arose from common
      precursors by divergence. The former families apparently arose at different times
      in evolutionary history, in different groups of organisms, employing different
      routes.

PMID- 7511374
TI  - Cloning and partial sequence analysis of a Mycoplasma synoviae DNA fragment
      encoding epitopes shared with the major adhesin P1 protein of Mycoplasma
      pneumoniae.
AB  - Polyclonal antibodies specific for the adhesin P1 protein of Mycoplasma
      pneumoniae were used to screen an expression library of M. synoviae genomic DNA
      constructed in the expression vector lambda gt11. Following several cycles of
      immunoscreening using the anti-P1 antiserum, a lambda gt11 recombinant clone
      containing 3.9 kilobase pairs (kbp) of M. synoviae DNA was identified and
      isolated from the expression library. Expression of the recombinant clone
      (designated MS-1) in Escherichia coli Y1089 followed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of the crude E. coli lysates revealed the
      presence of two novel proteins. Two antibodies that recognize the adhesin
      polypeptide--chicken anti-M. synoviae antibodies and anti-P1 antiserum--reacted
      with both proteins on immunoblots. Partial sequence analysis of the M. synoviae
      DNA in clone MS-1 and computer comparison of the predicted amino-acid sequences
      with existing protein sequence files revealed homology with the adhesin P1
      protein of M. pneumoniae.

PMID- 7511377
TI  - Paxillin: a cytoskeletal target for tyrosine kinases.
AB  - Paxillin is a recently identified member of the complex of cytoskeletal proteins
      that is found concentrated in cultured cells and in vivo at the cytoplasmic face
      of regions of cell attachment to the extracellular matrix. These sites, in view
      of their close proximity to the extracellular matrix, are well positioned to act
      as signal-transducing centers to 'report on' changes in the cells, immediate
      environment. Recent findings indicate that such signals are in part mediated
      through the activation of tyrosine kinases concentrated at the sites of adhesion.
      Changes in the phosphotyrosine content of paxillin accompanying this elevation in
      kinase activity suggest that paxillin may be an important intermediary in these
      pathways.

PMID- 7511378
TI  - Antiallergic profile of the novel H1-antihistaminic compound levocabastine.
AB  - Levocabastine hydrochloride (R50 547, CAS79516-68-0) caused no inhibitory effect
      on the histamine release from rat peritoneal mast cells induced by compound
      48/80, A23187 and concanavalin A. However, the drug inhibited histamine release
      from passively sensitized mast cells and passive peritoneal anaphylaxis in rats,
      though higher concentrations or doses were required. Moreover, levocabastine
      provided a relatively potent inhibitory effect on histamine release from lung
      pieces of actively sensitized guinea pigs exposed to antigen, and simultaneously
      the drug prevented a decrease in the cyclic AMP (cAMP) content. Levocabastine
      potently inhibited histamine-induced cutaneous reactions in rats and the drug
      also prevented histamine-induced contraction of isolated guinea pig ileum.
      Levocabastine did not induce any significant changes in platelet aggregation or
      in the contraction of guinea pig ileum induced by platelet activating factor
      (PAF). However, the drug inhibited eosinophil migration induced by PAF. The
      chemotaxis of neutrophils induced by N-formyl-methionyl-leucylphenylalanine
      (fMLP) was also inhibited by levocabastine in a dose-dependent fashion.
      Levocabastine has no influence on the order parameter tested with liposomes,
      suggesting that the drug provides no significant effect on the membrane fluidity
      of lipid bilayer. These results seem to indicate that the antiallergic effect of
      levocabastine is mainly dependent on its potent antihistaminic activity.

PMID- 7511379
TI  - Analysis of the characteristics of microheterogeneity of various serum
      glycoproteins in chronic alcoholics.
AB  - It has been reported that microheterogeneity of serum glycoproteins including
      transferrin is found in alcoholic liver disease. In the present study,
      microheterogeneity of serum glycoproteins in alcoholic liver disease patients was
      analysed using the Western blotting technique after isoelectric focusing.
      Microheterogeneity was found for serum alpha 1-antitrypsin, alpha 2
      macroglobulin, caeruloplasmin, alpha 1-acid glycoprotein and hemopexin as well as
      transferrin. Microheterogeneity disappeared following treatment with sialidase in
      some but not all glycoproteins. In hemopexin, microheterogeneity was recognized
      only after treatment with sialidase. These results suggest that mechanisms of
      microheterogeneity of serum glycoproteins in alcoholic liver disease may vary.
      One mechanism may be the interference of glycosylation of glycoproteins in the
      Golgi apparatus, and another may be the decrease of asialo-protein receptors in
      hepatocytes.

PMID- 7511375
TI  - Localization of sequences for the basal and insulin-like growth factor-I
      inducible activity of the fatty acid synthase promoter in 3T3-L1 fibroblasts.
AB  - Fatty acid synthase (FAS) plays a central role in fatty acid synthesis and its
      expression is under nutritional and hormonal control. We have investigated
      insulin-like growth factor-I (IGF-I) regulation of FAS by transfecting into 3T3
      L1 fibroblasts chimeric genes comprising the 5'-flanking region of the FAS gene
      linked to a luciferase (LUC) reporter gene. First, the basal promoter activity of
      the 5' serial deletions from nucleotides -318 to -19 of the FAS gene were
      compared. Deletions of the promoter sequences from -136 to -19 resulted in a step
      wise decrease in the promoter activity, with the -67 LUC and -19 LUC plasmids
      retaining 40% and 16% of the luciferase activity of -136 LUC. Regulatory
      sequences important for the FAS basal promoter activity in 3T3-L1 fibroblasts
      are, therefore, located within the -136 to -19 region. Treatment with 10 mM IGF-I
      also increased luciferase activity 1.8 +/- 0.2-, 1.8 +/- 0.3- and 2.5 +/- 0.1
      fold in 3T3-L1 fibroblasts transiently transfected with -136 LUC, -110 LUC and 
      67 LUC plasmids, respectively. Deletion of sequences from -67 to -19 resulted in
      the loss of responsiveness to IGF-I. Physiological doses of insulin (10 nM),
      however, did not increase luciferase activity in 3T3-L1 fibroblasts transfected
      with any of the above plasmids. Only upon treatment with pharmacological doses of
      insulin (1 microM), probably through IGF-I receptor, did luciferase activity
      increase 4.3 +/- 0.4-, 3.2 +/- 0.4- and 3.5 +/- 0.5-fold when transfected with 
      136 LUC, -110 LUC and -67 LUC plasmids, respectively; there was no increase with 
      19 LUC. The half-maximal effect of IGF-I on FAS promoter activity was observed at
      3 nM and a maximal effect was reached at 10 nM. These results indicate that the
      increased promoter activities observed are probably mediated through the IGF-I
      receptor. Furthermore, sequences responsible for IGF-I regulation of the FAS gene
      are located within the proximal promoter between nucleotides -67 and -19 of the
      FAS gene.

PMID- 7511380
TI  - Serum vitronectin receptor in alcoholic liver disease: correlation with
      fibronectin receptor and morphological features.
AB  - In order to clarify the significance of serum level of vitronectin receptor (VNR)
      in alcoholic liver disease (ALD), we have investigated the relationship with
      fibronectin receptor (FNR) and histological liver features in 21 ALD patients.
      Serum level of VNR and FNR was measured by enzyme immunoassay. Liver disease
      activity was scored based on levels of fibrosis and focal intralobular necrosis
      and degeneration. The serum level of VNR (micrograms/ml) was significantly higher
      in the patients with hepatic fibrosis (9.87 +/- 2.51) and liver cirrhosis (10.80
      +/- 1.52) than in normal subjects (5.51 +/- 0.52, P < 0.01) and fatty liver
      subjects (6.58 +/- 0.58, P < 0.05). A positive correlation was found between
      serum levels of VNR and fibronectin receptor (FNR) (P < 0.05). A positive
      correlation was observed between the serum level of FNR and the degree of hepatic
      fibrosis or focal intralobular necrosis and degeneration, while no correlation
      was found between the serum level of VNR and the degree of histological features.
      A positive correlation was also noted between the serum level of FNR and N
      terminal type III procollagen aminopeptide (PIIIP) (P < 0.001), while no
      correlation was observed between the serum level of VNR and PIIIP. We conclude
      that the serum level of VNR is increased in patients with advanced alcoholic
      liver disease. However, the mechanism by which serum levels of beta subunit of
      VNR and FNR are increased may be different.

PMID- 7511381
TI  - Chronic hepatitis C in alcoholic patients: studies with various HCV assay
      procedures.
AB  - Chronic hepatitis (CH) is one of the features of alcoholic liver disease (ALD).
      The role of hepatitis C virus (HCV) infection was investigated in 50 alcoholic
      patients with CH, employing various types of HCV antibody. All patients had a
      drinking history of more than 80 g/day of ethanol and the diagnosis of CH was
      made by liver histology within 2 weeks of abstinence. We assayed serum HCV using
      C100-3 antibody (Ortho EIA and RIA), the second generation (HCV-2nd) (DAINABOT
      EIA and PHA), and we also examined HCV-RNA by PCR. The positive rate of C100-3
      antibody was 56% by EIA and 66% by RIA. The HCV-2nd was much higher; 80% and 82%
      by EIA and PHA, respectively. The HCV-RNA was positive in 82% of patients. The
      positive rate for either of the HCV markers was 92% (46/50). In patients positive
      for C100-3, serum aminotransferase levels were still elevated even after
      abstinence and most of them showed chronic active hepatitis by liver histology.
      Follow-up liver biopsies showed histological progression even after abstinence.
      On the other hand, in some patients positive only for HCV-2nd and/or HCV-RNA,
      serum aminotransferase levels were normalized and histological improvement was
      observed soon after abstinence. These results suggest that histological
      determined CH in alcoholics is attributed mainly to the infection of HCV, HCV
      plays an important role in the histological deterioration after abstinence, and
      that the presence of C100-3 antibody reflects the activity of liver disease
      caused by HCV.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511382
TI  - Heterogeneity of hepatic acetaldehyde adducts in guinea-pigs after chronic
      ethanol administration: an immunohistochemical analysis with monoclonal and
      polyclonal antibodies against acetaldehyde-modified protein epitopes.
AB  - The formation of acetaldehyde (AcH) adducts was immunohistochemically
      demonstrated in the livers of experimental animals after chronic ethanol
      consumption. Recently, we established a hybridoma producing monoclonal antibody
      against the adduct. Although the polyclonal antibody obtained from a rabbit
      immunized with adducts had affinities for AcH adducts produced with 20 microM, 1
      mM and 10 mM of AcH, the monoclonal antibody could recognize only those produced
      with 1 and 10 mM of AcH, suggesting that there is a difference of antigenicity
      between the adducts formed with a high concentration of AcH and those modified
      with a low concentration of AcH. AcH adducts in the liver of guinea-pigs fed
      ethanol for 90 days were detected by immunohistochemical staining with the
      polyclonal and monoclonal antibodies. The staining of liver specimens with
      polyclonal antibody was observed around both the portal and perivenular areas,
      whereas the reactions to monoclonal antibody were localized only in the
      perivenular area. These data suggest that AcH adducts are able to be formed
      around both portal and perivenular areas in the liver and that the perivenular
      area might be exposed to a higher concentration of AcH than the portal area after
      ethanol intake.

PMID- 7511383
TI  - [The role of pro-inflammatory cytokines in recruiting inflammatory cells in the
      nose].
AB  - Cytokines and cell adhesion receptors play a pivotal role in the recruitment of
      cells from the peripheral blood into inflamed tissue. Allergic rhinitis has
      previously been described as an inflammatory reaction characterised by the
      migration of granulocytes into the nasal mucosa. Using this model, we
      investigated the release of proinflammatory cytokines (interleukin IL-1 beta, IL
      6, IL-8 and tumour necrosis factor-alpha TNF-alpha) and the expression of cell
      adhesion molecules (ELAM-1, ICAM-1 and LFA-1) in two studies involving biopsies
      as well as lavage and brush techniques. IL-1 beta and TNF-alpha can be found
      rapidly after allergen exposure and seem to initiate the cellular infiltration.
      The release of the chemokine IL-8 correlates with the continuously increasing
      number of granulocytes on the mucosal surface. Allergic rhinitis subjects showed
      significantly increased secretion levels of the proinflammatory cytokines IL-1
      beta and IL-6 and of the chemokine IL-8. These findings correspond to a higher
      expression of the adhesion receptors ELAM-1, ICAM-1 and LFA-1 in allergic mucosa.
      We conclude that proinflammatory cytokines regulate the cell infiltration by the
      induction of adhesion receptor expression.

PMID- 7511384
TI  - A model for health education.
AB  - A model for health education has been devised in Egypt on the basis of studies
      made in two villages. Its purpose is to contribute to the solution of
      environmental health problems by using locally available resources. Present
      indications are that the model will be applicable not only to the different
      sectors of the population, e.g., women and children, but also to many other
      villages throughout the country.

PMID- 7511385
TI  - Picture codes as discussion starters in AIDS education.

PMID- 7511386
TI  - Cysteine 17 of recombinant human granulocyte-colony stimulating factor is
      partially solvent-exposed.
AB  - Oh-eda et al. have shown instability of granulocyte-colony stimulating factor (G
      CSF) upon storage above pH 7.0 [J. Biol. Chem. (1990) 265, 11,432-11,435]. To
      clarify the mechanism of this instability, the accessibility of a free cysteinyl
      residue at position 17 for disulfide exchange reaction was examined using a
      sulfhydryl reagent. The results show that the cysteine is partially solvent
      exposed in both glycosylated and nonglycosylated forms, suggesting that the
      exposure of the cysteine plays a critical role in the instability of the protein.
      This is supported by the facts that at low pH where the cysteine is protonated,
      both proteins have much greater stability and that a Cys17-->Ser analog is
      extremely stable at neutral pH and 37 degrees C. It was observed that the rate of
      sulfhydryl titration is slower for the glycosylated form than for the
      nonglycosylated form, suggesting that the cysteine residue is less solvent
      exposed for the former protein or that the pKa is somewhat more basic. In either
      case, the carbohydrate appears to affect the reactivity of the sulfhydryl group
      through steric hindrance or alteration in local conformation. Both the
      glycosylated and nonglycosylated proteins showed essentially identical
      conformation as determined by circular dichroism, fluorescence, and infrared
      spectroscopy. Unfolding of these two proteins, induced either by guanidine
      hydrochloride or by pH, showed an identical course, indicating comparable
      conformational stability. Contribution of conformational changes to the observed
      instability at higher pH is unlikely, since little difference in fluorescence
      spectrum occurs between pH 6.0 and 8.0.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511388
TI  - Control of germinal vesicle breakdown in bovine x murine hybrid oocytes.
AB  - Bovine oocytes cultured in control medium or in medium containing dibutyrylcyclic
      adenosine monophosphate (dbcAMP) or an inhibitor of cyclic nucleotide
      phosphodiesterase (3-isobutyl-1-methylxanthine, IBMX) undergo germinal vesicle
      breakdown (GVBD). On the other hand, mouse oocytes remain arrested at the
      germinal vesicle (GV) stage when dbcAMP or IBMX is present. When 1 bovine GV
      stage oocyte is fused to 1 GV stage mouse oocyte, dissolution of both species GV
      occurred in dbcAMP-supplemented medium. Only when 4 to 5 GV stage mouse oocytes
      are fused to 1 GV stage bovine oocyte, and these giant cells are cultured in
      dbcAMP-medium, is maturation arrested with only GVs present in the cytoplasm. The
      inhibitory effect is more evident in IBMX-supplemented medium. Here nearly 50% of
      the fused cells exhibit GVs, both mouse and bovine, when 1 cattle GV oocyte is
      fused to 1 mouse GV oocyte and the fused cells are cultured for 24 h. Moreover,
      nearly all GVs are well preserved after fusion of 1 bovine oocyte to 2 or more
      mouse oocytes. When these hybrid cells after 24 h culture in IBMX are then washed
      and cultured in control medium for a further 24 h, GVBD occurred in all cells. We
      are of the opinion that this novel approach (ie mixing of sensitive and non
      sensitive cytoplasm) may in the future better explain the mechanisms involved in
      the regulation of mammalian oocyte maturation.

PMID- 7511387
TI  - Total synthesis, purification, and characterization of human [Phe(p-CH2SO 3Na)52,
      Nle32,53,56, Nal55]-CCK20-58, [Tyr52, Nle32,53,56, Nal55]-CCK-58, and [Phe(p
      CH2SO3Na)52, Nle32,53,56, Nal55]-CCK-58.
AB  - The synthesis of [Phe(p-CH2SO3Na)52, Nle32,53,56 Nal55]-CCK20-58, [Tyr52,
      Nle32,53,56, Nal55]-CCK-58 and of [Phe(p-CH2SO3Na)52, Nle32,53,56, Nal55]-CCK-58
      using the (9-fluorenylmethyloxy)-carbonyl (Fmoc) strategy on a 2,4-DMBHA resin is
      described. The crude peptide preparations were extremely complex when analyzed by
      RP-HPLC, capillary zone electrophoresis (CZE), and ion-exchange chromatography
      (IE-FPLC). We found that the most effective strategy for purification included
      cation-exchange chromatography followed by a RP-HPLC desalting step. The highly
      purified peptides (purity greater than 90%) were characterized by RP-HPLC, size
      exclusion HPLC (SEC), IE-FPLC, CZE, mass spectrometry, amino acid analysis, and
      Edman sequence analysis (for [Tyr52, Nle32,53,56, Nal55]-CCK-58). The results
      demonstrate the applicability of the 2,4-DMBHA resin for Fmoc solid-phase
      synthesis of long peptides amides (58 residues in length in this case) as well as
      the efficacy of an FPLC/RP-HPLC approach for the purification of very long,
      heterogeneous crude peptides, allowing a true assessment of the biological
      properties of these analogs to be carried out. [Phe(p-CH2SO3Na)52, Nle32,53,56,
      Nal55]-CCK20-58 was less than 1% as potent as CCK-8 while [Tyr52, Nle32,53,56,
      Nal55]-CCK-58 and [Phe(p-CH2SO3Na)52, Nle32,53,56, Nal55]-CCK-58 were inactive at
      the doses tested (< 0.01%).

PMID- 7511390
TI  - Onset of RNA synthesis and poly (A) content of early rabbit embryos. Comparison
      with sheep.
AB  - RNA synthesis in 2-32 cell embryos, as assessed by alpha-amanitin-sensitive 3H
      uridine incorporation, was first detectable in 4-cell stage rabbit and 8-cell
      stage sheep embryos. In the rabbit, uridine incorporation was detectable at the 2
      cell stage but was unaltered by alpha-amanitin, indicating synthesis of non
      polymerase II-dependent RNA species. Initiation of mRNA synthesis as determined
      by in situ hybridization with 3H-poly (U) probe was first detectable in late 2
      cell stage rabbit and 4-cell stage sheep embryos. In the rabbit embryos, nuclear
      labelling increased from the late 2-cell stage to the 16-cell stage, following a
      pattern similar to that of 3H-uridine incorporation. In contrast, the intensity
      of cytoplasmic labelling decreased from the 1- to the 8-cell stage and then
      increased up to the 32-cell stage. In sheep embryos, nuclear labelling by the
      poly (U) probe increased from the 4- to the 16-cell stage. It is concluded that
      initiation of transcription of the embryonic genome (mRNA) can be detected via
      the current methods used at the 4-cell stage in the rabbit and the 8-cell stage
      in the sheep.

PMID- 7511389
TI  - Cytochemical and immunocytochemical ultrastructural study of nucleoproteins
      during nucleologenesis in 8-cell bovine embryos.
AB  - The aim of this study was to characterize embryonic nucleologenesis by
      determining the appearance and localization of acid argyrophilic, basic lysine
      rich and histone proteins in 8-cell bovine embryos. Two silver staining
      techniques, ethanolic phosphotungstic acid (PTA) and immunocytochemical methods
      using specific antibodies, were applied at the ultrastructural level. The silver
      stained proteins were detected at the onset of nucleologenesis on the periphery
      of the dense nucleolus precursor bodies (NPBs). The amounts of these proteins
      increased during the transformation of the NPBs into the fibrillogranular
      nucleolus. At this stage the well-developed dense fibrillar components encircling
      fibrillar centres showed intense staining. PTA-positive (basic lysine-rich)
      proteins were present within most nucleolar structures during nucleologenesis as
      well as in the chromatin. Histones H2B, H3 and H4 were concentrated throughout
      the chromatin including the nucleolus-associated chromatin. At the onset of
      nucleologenesis, histones were absent in the NPBs. The first weak histone
      labelling was detected in the multivacuolated NPBs, both in the fibrous mass as
      well as inside the vacuoles. Nucleolar histones appeared with the massive
      penetration of DNA into the NPBs. We suggest that nucleologenesis may serve as a
      criterion of normal early embryonic development and that the proteins involved in
      the process of nucleologenesis and transcription could be used as chemical
      markers of nucleolar function.

PMID- 7511391
TI  - Escherichia coli-induced inhibition of endothelium-dependent relaxation and gene
      expression and release of nitric oxide is attenuated by chronic alcohol
      ingestion.
AB  - We examined the effect of chronic administration of ETOH on Escherichia coli
      mediated suppression of relaxation and nitric oxide (NO) production by the rat
      thoracic aorta (RTA) and gene expression for constitutive NO synthase (cNOS) by
      the adrenal gland. Chronic alcoholic rats ("alcoholic") were fed a diet
      containing ETOH as 36% of the caloric intake for 8-10 weeks. Nonalcoholic control
      rats ("control") were fed an isocaloric equivalent diet containing 36% dextrin.
      Alcoholic rats were given an injection of approximately approximately 10(10) live
      E. coli through a dorsal SC catheter 24 and 19 h before experimentation
      ("alcoholic-septic"), and control rats were treated in an identical manner
      ("septic"). The next day the rats were anesthetized with ketamine-xylazine (0.1
      ml/100 g rat) and rings of RTA were mounted in muscle chambers for isometric
      recording of force development. Rings of RTA were precontracted with an EC50
      concentration of phenylephrine, and relaxation to acetylcholine (ACh), A23187,
      and nitroglycerin were obtained. A23187- and ACh-induced relaxation was
      attenuated in RTA obtained from septic rats, whereas the relaxation to
      nitroglycerin was slightly enhanced. Chronic administration of ETOH attenuated
      the effects of E. coli on endothelium-dependent relaxation in alcoholic-septic
      rats. NO was measured with ozone chemiluminescence. Basal and stimulated NO
      production was attenuated in RTA obtained from septic rats and unaffected in RTA
      obtained from alcoholic or alcoholic-septic rats. cNOS was unmeasurable in
      adrenals from septic rats. ETOH increased mRNA for cNOS, an effect amplified in
      alcoholic-septic rats. Thus, E. coli inhibits endothelium-dependent relaxation
      and NO production, and ETOH attenuates these effects of E. coli on the
      endothelium-NO system, possibly by upregulating gene expression for cNOS.

PMID- 7511393
TI  - Standardized precision radiotherapy in choroidal metastases.
AB  - Metastases in the choroid of the eye are frequent in patients with disseminated
      malignancy. We here report the results using the precision radiotherapy technique
      described by Schipper et al. to treat 14 of 17 consecutive patients (21 eyes)
      with symptoms from such metastases. A beam defining collimator was used and a
      lateral field was given with the treated eye individually fixed. Varying
      fractionations and doses were used. The biologically effective dose for early
      effects (BED3) was 47 to 90 Gy and for late effects (BED10) 28 to 59 Gy. In 14
      eyes (82%) the metastases regressed completely. The visual acuity was stabilized
      or improved in all patients and none needed local surgery. Three patients
      developed signs of radiation retinopathy, but only in one case the visual
      function was compromised. With this standardized technique no individualized dose
      planning was needed, the risk of radiation cataract was minimized and a dry eye
      avoided.

PMID- 7511392
TI  - Cholinoceptive cells in rat cerebral cortex: somatodendritic immunoreactivity for
      muscarinic receptor and cytoskeletal proteins.
AB  - Adult rat telecephalon was surveyed for cells demonstrating immunopositivity for
      muscarinic receptor (M35 antibody), microtubule-associated proteins,
      neurofilaments, and brain-spectrin. Neurons immunostained for muscarinic receptor
      were found in frontal, parietal, temporal, and occipital isocortex where they
      accounted for approximately 15-16% of all neurons. This labeling involved a large
      proportion of layer V pyramidal cells, some layer III pyramidal cells and a small
      proportion of non-pyramidal cells in layers II-VI. In the hippocampus, pyramidal
      cells, non-pyramidal cells and granular cells were immunoreactive, as were many
      pyramidal cells in subicular and entorhinal cortices. In every cortical region
      examined, cells demonstrating muscarinic receptor were morphologically identical
      to cells stained lightly to moderately for acetylcholinesterase following
      pretreatment with diisopropylfluorophosphate, and they were found in similar
      numbers and in a similar laminar distribution. These characteristics further
      corresponded to those of cells whose somatodendritic compartments were intensely
      immunostained by antibodies to microtubule-associated proteins (MAP): MAP-1, MAP
      2, MAP-5; neurofilament proteins (NF): NF-68kD, NF-160kD, NF-200kD; and brain
      spectrin. Double immunostaining using a fluorescence method followed by an avidin
      biotin staining procedure revealed that cortical cells which possessed
      immunoreactivity for muscarinic receptor demonstrated an 80-85% overlap with
      cells that were immunoreactive for MAP-2 (and tau) or NF-200kD. Following
      unilateral ibotenic acid lesions of the nucleus basalis, MAP-2 immunostaining was
      reduced in the ipsilateral isocortex. This significant reduction was most evident
      in the parietal cortex, exactly where maximal loss of acetylcholinesterase
      containing fibers occurred. The same lesion produced no significant difference in
      immunodensity of muscarinic receptor, MAP-1, MAP-5 NF-68kD, NF-160kD and NF
      200kD. Thus, cortical cholinoceptive cells are enriched with cytoskeletal
      components and cholinergic afferents modulate cortical MAP-2.

PMID- 7511395
TI  - High antigenic cross-reactivity of the V3 consensus sequences of HIV-1 gp120.
AB  - The principal neutralization determinant (PND) of the human immunodeficiency
      virus type 1 (HIV-1) is located within the variable V3 region of the external
      envelope protein gp120. Although it is recognized that V3 sequences induce
      antibody response with restricted neutralization activity in vitro, we observed
      that the V3 consensus sequences representing North American/European and African
      isolates were highly cross-reactive, binding 94 and 77%, respectively, of sera
      collected from HIV-1 individuals originating from various parts of the world.
      Even HIV-1-positive sera from some East African residents, infected by strains
      whose V3 loop sequences are undoubtedly distinct from the North American/European
      consensus V3 loop sequence, reacted better to the V3 North American/European
      consensus peptide than to African-specific V3 sequences. Results indicate that
      the V3 consensus sequences represent the best candidates for optimal cross
      reactivity with a wide variety of strains. Furthermore, using immunoassays for
      antibodies to prototype-specific V3 sequences, it is shown that HIV-1 strains
      related to the MN group are prevalent in West Africa, indicating either a West
      African origin of the MN-related viruses or more probably an introduction of this
      group of viruses through European/North American contacts.

PMID- 7511394
TI  - Antigenic variation in gp120s from molecular clones of HIV-1 LAI.
AB  - To address the relationship between primary sequence variation in HIV-1 gp120 and
      its antigenic structure in a simple system, we have measured the binding of human
      and murine monoclonal antibodies (MAbs) to gp120 from four molecular clones of
      HIV-1 LAI: HxB2, HxB3, Hx10, and NL4-3. Despite the close relationship between
      these clones, and their relatively conserved gp120 sequences, there is
      considerable variation in their antigenic structure, judged by MAb reactivities
      to the V2, V3, and C4 domains and to discontinuous epitopes. Because of our prior
      studies of the determinants of MAb binding to HxB2 gp120, we can make reasonable
      estimates of how sequence variation among the LAI clone gp120s affects their
      binding of some MAbs; for other MAbs our current knowledge of gp120 structure is
      too limited to allow such estimates. These results indicate that small variations
      in primary gp120 amino acid sequence can profoundly affect recognition of this
      glycoprotein by all five groups of defined anti-gp120 neutralizing antibodies.

PMID- 7511396
TI  - Efficient antigen presentation to cytotoxic T lymphocytes by cells transduced
      with a retroviral vector expressing the HIV-1 Nef protein.
AB  - In the classic model of antigen processing and presentation, viral antigens must
      be synthesized within the cytoplasm of infected cells to be processed and
      presented to CD8+, MHC class I-restricted cytotoxic T lymphocytes (CTLs). We have
      examined the utility of a retroviral vector (pNeoNef) expressing the human
      immunodeficiency virus type (HIV-1)Lai Nef protein for the development of target
      cells to study HIV-specific CTLs. Autologous Epstein-Barr-transformed B cell
      lines (EBV-B cells) transduced with pNeoNef were efficiently lysed by CTL lines
      from donors capable of lysing EBV-B cells infected with a recombinant vaccinia
      virus (rVV) expressing Nef. Also, the transduced cells were efficient stimulator
      cells for the generation of Nef-specific CTL lines. The CTL lines thus generated
      recognized the same epitopes as CTL lines from the same donor generated by
      nonspecific stimulation. The use of similar cell lines transduced with retroviral
      vectors expressing HIV proteins may be useful in the study of CTLs in HIV
      infected donors and in the study of the ability of candidate vaccines, including
      rVV, to induce HIV-specific CTLs. As antigen-presenting cells, the cell lines may
      be useful in the generation of antigen-specific CTL lines.

PMID- 7511397
TI  - Haematopoietic growth factors in clinical medicine.

PMID- 7511398
TI  - Use of granulocyte growth factors in solid tumours.

PMID- 7511399
TI  - Single-dose and fractionated palliative radiotherapy for bone metastases.

PMID- 7511400
TI  - Palliation of malignant intestinal obstruction using octreotide.
AB  - Vomiting due to malignant intestinal obstruction is an unpleasant terminal event
      in many cancer patients, which responds poorly to conventional therapies.
      Somatostatin and its long-acting analogues reduce intestinal secretion. For this
      reason, octreotide was used in a phase I/II study of patients with intractable
      vomiting secondary to intestinal obstruction due to malignant disease. Vomiting
      was controlled or the volume of nasogastric aspirate was markedly reduced in 18
      of 24 (75%) patients receiving a subcutaneous infusion of octreotide (median
      initial dose 300, range 100-600 micrograms/day) for a median of 9.4 (range 1-38)
      days. A further 2 patients had partial relief of their symptoms. Octreotide is an
      effective treatment of nausea and vomiting due to malignant bowel obstruction.

PMID- 7511401
TI  - Second-line treatment with ifosfamide and carboplatin in patients with ovarian
      carcinoma relapsing after treatment with carboplatin.
AB  - 20 patients with ovarian carcinoma whose disease had relapsed (1-42 months,
      median 4 months) after showing either response or stable disease to carboplatin,
      were treated with ifosfamide (5 g/m2 intravenously over 24 h, day 1) and
      carboplatin (200 mg/m2 intravenously day 2) as second-line treatment. The mean
      number of treatment cycles was 3.5 (range 1-6). The major toxicities were
      thrombocytopenia (WHO grade 3/4, 25%), neutropenia (WHO grade 3/4, 40%) and
      encephalopathy (WHO grade 3/4, 15%). Overall response rate was 15% [complete
      response, 0; partial response, 3 (15%); no change, 5 (25%) and progressive
      disease, 12 (60%)]. The median survival from the date of second-line treatment
      was 7 months. This combination offers no advantage over either agent used alone.

PMID- 7511402
TI  - Postoperative chemotherapy increases the disease-free survival rate in primary
      gastric lymphomas stage IE and IIE.
AB  - We describe 53 patients with primary gastric non-Hodgkin's lymphoma (38 stage
      IE,15 stage IIE) treated with surgery as a primary procedure. According to the
      Working Formulation, 13 cases had low, 21 had intermediate and 19 had high grade
      malignancy. 34 patients considered at high risk received postoperative
      polychemotherapy. The overall 10-year disease-related survival is 91%. Median
      follow-up is 52 months. 7 patients relapsed (13%). The 10-year disease-free
      survival rate of the 19 patients initially treated with surgery is 60%, as
      compared with 92% in the patients who also received chemotherapy (P = 0.004).
      However, overall survival did not differ between the two groups, since two-thirds
      of the patients who relapsed after surgery alone were rescued with chemotherapy.
      Stage, age, sex and histology did not correlate with survival. In our experience,
      surgery was an adequate first step procedure; the addition of chemotherapy
      significantly reduced relapses and increased the disease-free survival rate in
      patients with unfavourable prognostic factors.

PMID- 7511403
TI  - Simple cytokeratins in the serum of patients with lung cancer: relationship to
      cell death.
AB  - An important role in differentiation and proliferation has been demonstrated for
      the 20 cytokeratin (CK) polypeptides. The serum of 24 patients with biopsy-proven
      non-small cell lung cancer (NSCLC) and a similar number of controls was examined
      for evidence of CK8 and CK18. Using enzyme-linked immunosorbent assay (ELISA),
      all the control sera were negative, but 9 of the 24 patients were positive (mean
      2.62 ng/ml; range 1.4-5.8; P = 0.0036). Western blotting confirmed the results of
      the ELISA in all cases, and indicated full size CK polypeptides. Advanced stage
      disease patients were more likely to be seropositive (P = 0.00024). Biopsy
      specimens showed CK8 expression in all 24 cases by immunochemistry and CK18 in 22
      cases. This is the first study to demonstrate that a subgroup of NSCLC patients
      have intact CK8 and CK18 peptides in their serum, and their detection may
      correlate with advanced disease.

PMID- 7511404
TI  - Cholera. Update, end of 1993.

PMID- 7511405
TI  - Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene:
      earliest events at ectopic injection sites.
AB  - Human Platt neuroblastoma cells were transfected with the marker gene, bacterial
      lacZ, to track cells at the earliest stages after ectopic injection at two
      different sites in athymic nude mice. Three clones (LZPt-1,-2 and -3) of
      differing morphologies were analysed. All clones yielded large primary tumours
      subcutaneously or intradermally with similar latency. While LZPt-2 and -3 clones
      generated well-staining primary tumours, LZPt-1 cells yielded many non-staining
      tumours, indicating greater instability of lacZ expression for this clone in situ
      (stability of lacZ expression in culture was similar for all three clones). After
      s.c. or intradermal injections, tumour cells were tracked for 1 h to > 3 weeks
      (palpable) to evaluate the topology and population expansion characteristics at
      the earliest times. From 1 h to 2 days, tumour cells were concentrated in central
      masses with 'crinkly hair' distributions emanating from the periphery. Between 3
      and 7 days, these 'crinkly hair' patterns were cleared from the tissue, leaving
      dense ovoid patterns of tumour cells. These concentrations of cells expanded
      collectively, not by division of one or a few cells, but by division of many
      cells. For clone LZPt-1, cells stained well with X-gal for 2-3 days; by 7 days,
      most cells were non-staining. Evidence suggests that lacZ expression is turned
      off in these tumour cells, rather than a lacZ- cell type clonally dominating the
      population. For all three clones, tumour cells remained rounded and did not
      spread in any tissue environment at all time points, indicating very different
      matrix adhesion mechanisms operating in situ compared with their distinctive
      spreading patterns in culture. Angioneogenesis near primary tumours became
      evident by 2-3 days, leading to extensive vascularisation by 1-2 weeks. Overall,
      these studies indicate common tumour progression characteristics for three
      different clones of human neuroblastoma, insight into lacZ instability mechanisms
      operating in one of these clones and the earliest events in primary tumour
      formation for this tumour at two different ectopic sites.

PMID- 7511407
TI  - Mast-cell histamine is angiogenic through receptors for histamine1 and
      histamine2.
AB  - The activation of mast-cells in situ induces angiogenesis in normally
      vascularized, adult mammalian tissue. Since the secreting mast-cell
      characteristically releases histamine, we studied the possible role of histamine
      in the outcome of mast-cell mediated angiogenesis using the rat mesenteric window
      assay. One H1-receptor antagonist, brompheniramine maleate (BPA), and one H2
      receptor antagonist, metiamide, were separately administered systemically (s.c.)
      at non-toxic doses during the period of angiogenesis induction. Angiogenesis was
      effected by i.p. injections of the mast-cell secretagogue compound 48/80 for 5
      consecutive days. The animals were killed 14 days after the start of the i.p. and
      s.c. treatment, close to the middle of the expanding angiogenic phase of the
      angiogenic reaction studied. Angiogenesis was quantified in terms of (a) the
      number of vessel profiles per unit tissue length (No/UL), which reflects mainly
      the degree of branching and/or tortuosity, (b) the relative vascularized area
      (VA), which is a measure of spatial extension, and (c) the vascular density (VD),
      a measure of vessel density per unit area of vascularized tissue. Whereas BPA
      significantly suppressed No/UL, metiamide significantly reduced No/UL and VD in
      statistical terms suggesting that endogenous mast-cell histamine is angiogenic
      through both H1- and H2-receptors. This appears to be the first paper to report
      that the occupancy of H2-receptors is angiogenic.

PMID- 7511406
TI  - Comparative expression of fibroblast growth factor mRNAs in benign and malignant
      breast disease.
AB  - The messenger RNAs for the angiogenic acidic and basic fibroblast growth factors
      are expressed at a significantly higher level in samples of human benign
      neoplastic and hyperplastic tissue than in samples from breast cancers. However,
      approximately one in four malignant breast cancer samples contain basic
      fibroblast growth factor mRNA at the same level as in the benign lesions when
      basic fibroblast growth factor mRNA levels are corrected with respect to levels
      of expression of glyceraldehyde-3-phosphate dehydrogenase mRNA. A similar
      proportion of human malignant breast cancer cell lines express a high level of
      basic fibroblast growth factor mRNA. The results suggest that some malignant
      breast cancers and their constitutive carcinoma cells express abundant levels of
      basic fibroblast growth factor mRNA. The resultant production of basic fibroblast
      growth factor by breast cancer cells within some tumours may contribute to their
      development.

PMID- 7511408
TI  - The purification of 11 beta-hydroxysteroid dehydrogenase from mouse liver
      microsomes.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) is a microsomal enzyme complex
      responsible for the interconversion of active 11-hydroxy glucocorticoids to
      inactive 11-oxo metabolites. It has long been controversially discussed whether
      11-dehydrogenation and 11-oxoreduction are catalysed by a single bidirectional
      enzyme or if the 11 beta-HSD system comprises 2 kinetically distinct microsomal
      enzyme activities, 11-dehydrogenase and 11-oxoreductase. However, 11-oxoreduction
      of homogeneously purified 11 beta-HSD could not be demonstrated under in vitro
      conditions until today. We have purified 11 beta-HSD from mouse liver microsomes
      to homogeneity by a purification method which affords a gentle membrane protein
      solubilization as well as providing a favourable detergent surrounding during the
      various chromatographic steps. Following 11-dehydrogenation of corticosterone and
      11-oxoreduction of dehydrocorticosterone simultaneously throughout the entire
      purification procedure we could demonstrate that 11 beta-HSD retains both
      oxidative and reductive activities in almost the same ratio, which is also true
      for the homogeneously purified enzyme. Deducing from the coincidentally
      increasing specific activities of 11-dehydrogenation and 11-oxoreduction the
      conclusion can be drawn that both activities reside within the same protein.
      Furthermore, in addition to NADP(H) also NAD(H) can serve as cosubstrate, which
      is mainly true for the oxidative direction. In conclusion, our results provide
      evidence that the oxidative and reductive behaviour of 11 beta-HSD can be
      explained by the concept of a unique, reversible oxidoreductase thus disproving
      the two enzyme theory.

PMID- 7511410
TI  - Fidelity of in vitro DNA strand transfer reactions catalyzed by HIV-1 reverse
      transcriptase.
AB  - The fidelity of DNA strand transfer reactions catalyzed by human immunodeficiency
      virus type 1 reverse transcriptase has been studied in vitro. A model system
      involving two sequential DNA strand transfers was developed to simulate the
      process of forced copy-choice recombination. A propensity for nucleotide
      misincorporation at the junction of the strand transfer, as determined by DNA
      sequencing of the reaction products, was found consistent with a model involving
      the addition of nontemplate-directed nucleotides prior to the transfer of nascent
      DNA onto the accepting RNA template [Peliska, J. A., & Benkovic, S. J. (1992)
      Science 258, 1112]. The kinetic and mechanistic factors that may dictate which
      nucleotide bases are incorporated at recombination sites during strand transfer
      and the possible consequences of recombination-induced mutagenesis in vivo are
      discussed.

PMID- 7511409
TI  - Calcium and protein kinase C regulation of the glucocorticoid receptor in mouse
      corticotrope tumor cells.
AB  - The effect of increasing intracellular free calcium and activating protein kinase
      C on glucocorticoid receptor (GR) expression was investigated in AtT-20 cells, a
      mouse corticotrope tumor cell line. Treatment of AtT-20 cells with the calcium
      ionophore A23187 induced a rapid time- and dose-dependent decrease in
      [3H]dexamethasone ([3H]DEX) binding when measured in intact cells. Binding fell
      to 16% of control following 3 h of treatment with 10 microM A23187. In contrast,
      A23187 did not acutely effect steady state levels of GR mRNA, although levels
      fell to 76 +/- 1% of control after 8-15 h of treatment. Scatchard analysis of
      A23187 treated cultures demonstrated a decrease in GR binding capacity but no
      change in affinity for [3H]DEX. Acute inhibition of protein synthesis with
      cycloheximide had no effect on [3H]DEX binding, suggesting that the calcium
      dependent decrease was not simply due to inhibition of GR protein synthesis. In
      contrast to the A23187 induced decrease in [3H]DEX binding in intact cells, when
      binding was measured in cytosol extract from A23187 treated cultures there was no
      decrease. These data suggest that the A23187 induced decrease in GR binding in
      whole cells is not due to a decrease in GR protein but reversible conversion of
      the receptor to a non-binding form. Inducing calcium influx only through L-type
      voltage-dependent calcium channels with BAY K8644 also decreased [3H]DEX binding
      at AtT-20 cells, though the effect was less than that induced by A23187. Although
      activation of protein kinase C with phorbol ester transiently increases
      intracellular free calcium in AtT-20 cells, when cells were treated for 0.5 to 22
      h with phorbol 12-myristate 13-acetate, there was no acute fall in [3H]DEX
      binding, and only a small decrease following 16 h of treatment. These data
      demonstrate that sustained increases in intracellular calcium in corticotropes
      can induce a rapid and marked decrease in GR binding. The mechanism is post
      translational and involves the reversible conversion of the receptor to a non
      binding form. In addition, the cellular milieu is clearly important in conferring
      non-binding status on GR since once the cell is disrupted GR binding is restored.

PMID- 7511411
TI  - Nuclear DNA helicase II unwinds both DNA and RNA.
AB  - Nuclear DNA helicase II (NDH II) has been purified to near-homogeneity by
      exploiting its high affinity to poly[(rI).(rC)]-agarose. The purified enzyme was
      obtained as two catalytically active forms of 130- and 100-kDa molecular mass,
      respectively. After treatment with cyanogen bromide, the separated polypeptides
      displayed very similar digestion patterns. Thus, the 100-kDa form most likely is
      a proteolytic product of the 130-kDa polypeptide. For DNA unwinding, NDH II could
      use any of the four rNTPs or dNTPs with Km values between 20 and 100 microM. DNA
      unwinding was stimulated up to 20-fold by substrates that contained single
      stranded 3'-tails. NDH II-catalyzed DNA unwinding was strongly inhibited by RNA,
      but was little affected by DNA. The strongest RNA inhibitor, poly[(rI).(rC)], was
      also the strongest effector of the NTPase activity of NDH II. The binding
      constant for poly[(rI).(rC)] binding was about 2 x 10(7) M-1; the minimal binding
      site size was determined as 16 nucleotides. In agreement with its high affinity
      to RNA, NDH II unwound double-stranded RNA. RNA unwinding required the presence
      of a nucleoside triphosphate and a divalent cation (Mg2+). Thus, like the
      prototypic replicative helicase large T antigen of simian virus 40, NDH II may
      function in both DNA and RNA unwinding.

PMID- 7511412
TI  - Rapid refolding of native epitopes on the surface of cytochrome c.
AB  - Refolding of surface epitopes on horse cytochrome c has been measured by
      monoclonal antibody binding. Two antibodies were used to probe re-formation of
      native-like surface structure: one antibody (2B5) binds to native cytochrome c
      near a type II turn (residue 44) while the other (5F8) binds to a different
      epitope on the opposite face of the protein near the amino terminus of an alpha
      helical segment (residue 60). The results show that within the first
      approximately 100 ms of refolding all of the unfolded protein collapses to native
      like folding intermediates that contain both antibody binding sites. All three
      absorbance/fluorescence-detected kinetic phases in the folding of cytochrome c
      (k1 approximately 5 s-1, k2 approximately 0.4 s-1, k3 approximately 0.03 s-1) are
      slower than the rates of re-formation of the antibody binding sites (k(obs) >
      10.0 s-1), suggesting that the formation of antibody binding sites precedes the
      refolding reactions observed in kinetically resolved optically-detected refolding
      phases. Kinetically unresolved folding processes account for 79% and 19% of the
      total fluorescence change and absorbance change, respectively, observed in
      equilibrium unfolding. Thus, kinetically unresolved folding reactions appear to
      be responsible for re-formation of the MAb binding sites within partially folded
      intermediate species. These species are non-native (incompletely folded) in that
      their optical properties are in between those of the unfolded and the fully
      folded protein. As a test of whether antibody binding to folding intermediate(s)
      perturbs further folding, the rate of the absorbance-detected slow refolding
      phase has been measured for folding intermediate(s) of cytochrome c complexed
      with antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511413
TI  - Structure of micelle-associated alamethicin from 1H NMR. Evidence for
      conformational heterogeneity in a voltage-gated peptide.
AB  - Alamethicin is a 20 amino acid peptide that produces a voltage-dependent
      conductance in membranes. To understand the mechanism by which this peptide
      becomes voltage-gated, the structure of alamethicin bound to micelles was
      examined using high-resolution 1H nuclear magnetic resonance (NMR). Two
      dimensional correlation and nuclear Overhauser effect spectroscopy (NOESY) were
      carried out on alamethicin incorporated into perdeuterated sodium dodecyl sulfate
      (SDS) micelles, and the 1H NMR spectrum of the peptide in micelles was assigned.
      The intensities of the HN-HN(i,i+1), H alpha-HN(i,i+1), H alpha-NH(i,i+3), H
      alpha-H beta (i,i+3), and H alpha-NH(i,i+4) cross peaks in the NOESY spectrum
      suggest that the N-terminal half of the peptide is predominantly alpha-helical,
      while the C-terminal half has a less regular or more flexible structure. The
      exposure of micelle bound alamethicin to the aqueous solution was determined by
      examining the effect of aqueous paramagnetic reagents on the line widths of the
      peptide protons. These measurements suggest that alamethicin is buried in the
      micelle. A set of restraints consisting of 175 distances (derived from NOESY
      spectra), five dihedral angles, and two hydrogen bond distances were used in a
      simulated annealing procedure that yielded structures for micelle associated
      alamethicin. The structures that were generated with simulated annealing were
      largely helical from residues 4-9 and 12-16. A limited number of structural forms
      were obtained. The main difference among forms involved the backbone
      conformations of MeA10, Gly11, and Leu12 and resulted in structures that were
      straight or had different amounts of bend. The structural forms could be easily
      interconverted by rotation of the psi and phi angles of residues 10-12. The
      rotational freedom at or near MeA10 may be a result of Pro14, which would be the
      normal hydrogen-bonding position for the peptide carbonyl of MeA10. These results
      suggest that conformation rearrangements at or near MeA10 may play a role in the
      voltage-gating of alamethicin.

PMID- 7511415
TI  - Functional principles of solute transport systems: concepts and perspectives.

PMID- 7511414
TI  - Phosphorylation by cAMP-dependent protein kinase causes a conformational change
      in the R domain of the cystic fibrosis transmembrane conductance regulator.
AB  - Individuals with cystic fibrosis have a defect in the CFTR protein, a chloride
      channel regulated by cAMP-dependent protein kinase (PKA). The majority of the
      phosphorylation sites of PKA are located in the R domain of CFTR. It has been
      postulated that this domain may act as a gate for the chloride channel. Of the
      many possible mechanisms whereby the R domain could gate the channel, including
      interdomain interactions, charge distribution, or conformational change, we
      investigated the possibility that phosphorylation leads to conformational changes
      in the R domain. To test this hypothesis, a protocol for purification of human R
      domain peptide synthesized in a bacterial expression system was developed.
      Purified R domain was phosphorylated by PKA, and CD spectra were obtained. As a
      result of phosphorylation by PKA, a significant spectral change, indicative of a
      reduction in the alpha-helical content, was found. CD spectra of the R domain of
      a shark homologue of CFTR indicated similar changes in conformation as a result
      of phosphorylation by PKA. In contrast, phosphorylation of the human R domain by
      PKC, which has only a small influence on CFTR channel activity, failed to elicit
      CD spectral changes, indicating no conformational change comparable to those
      induced by PKA phosphorylation. These observations provide the first structural
      characterization of the R domain and suggest that the gating of the CFTR chloride
      channel by PKA may involve a conformational change in the R domain.

PMID- 7511416
TI  - The effects of drugs on the incorporation of a conformationally-sensitive,
      hydrophobic probe into the ion channel of the nicotinic acetylcholine receptor.
AB  - The pattern of incorporation of the hydrophobic photolabel 3-(trifluoromethyl)-3
      (m-[125I]iodophenyl)diazirine([125I]TID) into the nicotinic acetylcholine
      receptor (AChR) is a sensitive measure of AChR conformation (resting state or
      desensitized). We determined the ability of tetracaine, dibucaine, procaine,
      lidocaine, chlorpromazine or phencyclidine to inhibit [125I]TID photolabeling of
      the AChR as a function of drug concentration, both as a measure of the ability of
      these drugs to desensitize the AChR, and to characterize the [125I]TID binding
      site. To localize the site(s) of drug action, experiments were performed in the
      absence and presence of saturating concentrations of alpha-bungarotoxin (BgTx),
      to block drug binding to the agonist binding site. On the basis of the
      concentration dependence of their effects, which was not altered by the presence
      of BgTx, tetracaine and dibucaine appeared to block [125I]TID incorporation
      competitively, suggesting that the high-affinity [125I]TID binding site is the
      non-competitive blocker binding site presumed to exist in the interior of the
      AChR ion channel. Procaine, chlorpromazine, lidocaine and phencyclidine blocked
      [125I]TID incorporation at lower concentrations in the absence of BgTx than in
      its presence, suggesting that these drugs block incorporation by inducing
      desensitization when bound to their high-affinity non-competitive blocker binding
      sites and that BgTx countered the drug effect by allosterically stabilizing the
      resting state.

PMID- 7511417
TI  - Immunohistochemical localization of insulin-like growth factor (IGF-I), IGF-I
      receptor, and IGF binding proteins 1-4 in human fallopian tube at various
      reproductive stages.
AB  - Despite the existence of numerous data regarding the insulin-like growth factor
      (IGF) system in reproductive tissues, especially uterine and ovarian, very little
      information is available concerning their presence in oviductal/fallopian tube
      tissue. To elucidate this, the present study was undertaken to determine the
      presence and cellular distribution of IGF-I, IGF-I receptor (IGF-IR), and IGF
      binding proteins (IGFBP) 1-4 in human fallopian tubes during various reproductive
      stages, by means of immunohistochemical analysis with specific antibodies to IGF
      I, IGF-IR and IGFBPs 1-4. The primary site of immunoreactivity for these proteins
      in fallopian tube tissue was in the epithelial lining of the tubes, with
      substantially lower intensity in the smooth muscle layer, fibroblasts of the
      serosal tissue, and arteriolar endothelial and smooth muscle cells. The
      immunostaining was associated with both ciliated and nonciliated tubal epithelial
      cells without substantial differences in their intensity. There were also no
      differences in immunoreactivity of IGF-I, IGF-IR, and IGFBPs 1-4 present in
      ampullary vs. isthmus region of the tubes. Specimens obtained 5-12 years post
      tubal ligation stained similarly to sections from unligated tubes taken during
      the same phase of the cycle. The intensity of immunostaining for the IGFBPs was
      greatest for IGFBP-1, followed by IGFBP-4, then IGFBP-2 and IGFBP-3, with 2 and 3
      having similar intensities. The immunostaining intensity of IGF-I, IGF-IR, and
      IGFBPs in fallopian epithelial cells was cycle-dependent and considerably higher
      in late proliferative and early-mid secretory compared to late secretory phases,
      with little immunostaining in the early proliferative phase of the menstrual
      cycle and postmenopausal period. In summary, the immunohistochemical study
      reported here demonstrates the presence of IGF-I, IGF-IR, and IGFBPs 1-4 in the
      human fallopian tube during various reproductive stages. These data suggest an
      autocrine/paracrine role for the IGF-I system in fallopian tube function, and
      their cyclic dependency further implies ovarian steroidal regulation.

PMID- 7511419
TI  - Poly(A)+ ribonucleic acids are enriched in spermatocyte nuclei but not in
      chromatoid bodies in the rat testis.
AB  - To determine whether male germ cells contain specific storage sites for poly(A)+
      RNAs, in situ hybridizations were performed with sections of rat testis and a
      [3H]polyuridylic acid probe. The highest levels of poly(A)+ RNA were found in
      spermatocytes and round spermatids, while lower levels of poly(A)+ RNA were
      detected in spermatogonia, elongated spermatids, Sertoli cells, myoid cells,
      fibroblasts, macrophages, and Leydig cells. No poly(A)+ RNA was detected in
      residual bodies of elongated spermatids. At stages IX-XI of the seminiferous
      cycle, the nuclei and cytoplasm of pachytene spermatocytes contained
      approximately equal amounts of poly(A)+ RNA, suggesting nuclear RNA storage
      and/or a reduced processing rate of mRNA precursors at this stage of germ cell
      differentiation. To examine the distribution of poly(A)+ RNAs in subcellular
      components of testicular cells, electron microscope radioautography was used. In
      germ cells and Sertoli cells, poly(A)+ RNA was often seen free in the cytoplasm
      or associated with the endoplasmic reticulum and was only occasionally found
      associated with mitochondria, lysosomes, lipid inclusions, and axonemes. As
      previously reported for the mRNAs of transition protein 1 and protamine 1
      [Morales et al., J Cell Sci 1991; 100:119-131], no compartmentalization of
      poly(A)+ RNAs was detected in the cytoplasm of round and elongated spermatids. No
      poly(A)+ RNA was detected in association with the radial body and in most
      sections, the chromatoid body did not contain any significant amounts of poly(A)+
      RNA.

PMID- 7511418
TI  - Effect of somatotropin and/or equine chorionic gonadotropin on serum and
      follicular insulin-like growth factor I and insulin-like growth factor binding
      proteins in cattle.
AB  - We investigated the effect of administration of somatotropin (ST) and/or eCG on
      insulin-like growth factor I (IGF-I) and IGF-binding proteins (IGFBP) in serum
      and follicular fluid (FFL) of cattle actively immunized against growth hormone
      releasing factor (GRF). Cyclic beef cattle, previously immunized against GRF-(1
      29)-Gly-Gly-Cys-NH2 conjugated to human serum albumin (synthesized and provided
      by Hoffmann-LaRoche, Inc., Nutley, NJ; GRFi, n = 31) or to human serum albumin
      alone (HSAi, n = 26), received (i.m.): 1) 25 mg recombinantly derived methionyl
      somatotropin (rbST, n = 14; sometribove provided by Monsanto Co., St. Louis, MO);
      2) 1100 IU eCG (n = 10); 3) rbST and eCG (rbST-eCG, n = 15); or 4) vehicle (VEH,
      n = 17) at 0 and 24 h after receiving prostaglandin F2 alpha (PGF2 alpha). Serum
      samples were collected at 0 and 40 h after PGF2 alpha, and the ovary bearing the
      largest follicle (DOM) was removed 44.0 +/- 0.5 h after PGF2 alpha; FFL was
      harvested from DOM and the subordinate follicle (SUB). Before treatment (0 h),
      GRFi cows had lower serum ST (0.6 +/- 0.2 vs. 2.2 +/- 0.2 ng/ml; p < 0.01) and
      IGF-I (26 +/- 4 vs. 72 +/- 4 ng/ml; p < 0.01), but greater IGFBP-2 (594 +/- 48
      vs. 384 +/- 52 ng/ml; p < 0.01) than HSAi cows. Serum and FFL concentrations of
      IGF-I or IGFBP-2 were not different between rbST- and rbST-eCG-treated cows or
      between VEH- and eCG-treated cows at Hour 40 after the initial treatment
      injection; therefore, data were combined and designated as rbST and VEH,
      respectively. Serum IGF-I was increased to a greater extent (percentage increase
      above 0 h) by rbST treatment in GRFi (362 +/- 24) than in HSAi (176 +/- 16) cows
      (immunization by treatment, p < 0.01). Across GRFi and HSAi, rbST lowered serum
      IGFBP-2 (342 +/- 31 vs. 541 +/- 27 ng/ml, rbST vs. VEH; p < 0.01). Diameters of
      DOM or SUB were not affected by immunization or treatment. Concentrations of IGF
      I and IGFBP-3 (determined by ligand blot analysis) in FFL from both DOM and SUB
      were lower (p < 0.05) in GRFi than in HSAi cows. In contrast, IGFBP-2 in FFL was
      elevated in SUB, but not DOM, in GRFi compared to HSAi cows.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7511420
TI  - Influence of fetectomy on serum pregnancy-associated plasma protein-A
      concentrations in the baboon.
AB  - In baboons as in humans, the placenta is a source of various peptides, including
      pregnancy-associated plasma protein-A (PAPP-A). However, our present
      understanding of the regulation of PAPP-A production is incomplete. We have
      demonstrated that after fetectomy, the baboon placenta retains steroidogenic
      capacity and is maintained in utero until delivered spontaneously close to term.
      We have suggested, therefore, that fetectomy provides a valuable in vivo approach
      to elucidating the role(s) of the fetus, and of the hormones (e.g., estrogen and
      progesterone) dependent upon the presence of the fetus, in the regulation of
      placental steroidogenesis during primate pregnancy. Therefore in the present
      study we utilized the fetectomy model to evaluate the respective roles of the
      fetus, estrogen, and progesterone on placental PAPP-A. Estradiol, progesterone,
      and PAPP-A concentrations were determined by RIA in maternal blood collected
      under ketamine anesthesia on Days 78-100 (n = 5), Days 102-144 (n = 4), and Days
      146-164 (n = 3) of gestation (term = Day 184) in control baboons (Papio anubis)
      and on Days 110-164 in baboons fetectomized on Day 100 (n = 9). Studies were also
      conducted in five animals in which placental estrogen was increased by maternal
      treatment on Days 70-100 with androstenedione and in three animals treated on
      Days 140-164 with the antiestrogen, ethamoxytriphetol (MER-25; 25 mg/day/kg
      BW).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511421
TI  - CCK-containing paraneurons in human adenomatous prostate.
AB  - The presence of CCK-containing neuroendocrine cells in human adenomatous
      prostates, and the colocalization of CCK together with serotonin in the same
      cell, have been demonstrated by means of an immunohistochemical technique and by
      a double labeling immunofluorescent staining. CCK-containing neuroendocrine cells
      had a focal distribution in the prostates and sometimes showed dendrite-like
      cytoplasmic processes. The major part of CCK (96.55%) colocalized with serotonin.
      CCK probably stimulates muscle contraction and endocrine/exocrine secretions in
      the urogenital tract.

PMID- 7511423
TI  - Effects of adenosine on chronotropic responses of rat atria to alpha and beta
      adrenergic stimulation.
AB  - The chronotropic response of rat atria to beta adrenergic stimulation required
      higher concentrations of agonist in the presence of adenosine. This anti beta
      adrenergic effect could attenuate the tachycardia induced by the increased
      sympathetic tone during cardiac ischemia. The sensitivity to alpha adrenergic
      stimulation did not change in the presence of adenosine.

PMID- 7511422
TI  - Characteristics of thiamin transport in the isolated perfused guinea pig heart.
AB  - The cellular uptake of (14C)-thiamin hydrochloride was studied in the isolated
      perfused guinea pig heart, using the rapid single circulation, paired-tracer
      technique, in which D-(3H)-mannitol serves as an extracellular marker. Cellular
      uptake of this vitamin was estimated by directly comparing venous dilution
      profiles of (14C) and (3H) radioactivities in the absence and presence of
      unlabelled thiamin hydrochloride and pyrithiamin hydrobromide. The maximal
      cellular uptake (Umax) of thiamin was very low (5.31 +/- 1.79%), while in the
      presence of 10 mM unlabelled thiamin and 1 mM pyrithiamin, Umax was significantly
      greater (9.71 +/- 1.57% and 12.30 +/- 0.82%, respectively). Our data suggest that
      there is a saturable mechanism of sarcolemmal thiamin transport out of myocardial
      cell, while this transport into the cell is unsaturable.

PMID- 7511424
TI  - Inhibitory role of cholinergic agonists on testosterone secretion by purified rat
      Leydig cells.
AB  - The effects of cholinometics on basal or hCG-induced testosterone (T) release by
      Percoll-purified Leydig cells of the rat were studied. Acetylcholine and
      carbachol as well as nicotine decreased basal and hCG-induced T secretion. The
      ganglionic nicotine antagonist hexamethonium promoted a partial reversal of the
      inhibitory effect of nicotine on basal or hCG-stimulated T secretion. Atropine
      also reduced the inhibitory effect of carbachol on basal or stimulated androgen
      release. These data indicate that, in short-term incubations, testosterone
      released by purified Leydig cells is inhibited by nicotinic and muscarinic
      cholinergic agonists, thus supporting the hypothesis that parasympathetic
      autonomic system may be involved in the negative regulation of testicular
      androgen secretion.

PMID- 7511425
TI  - Comparative effects of bradykinin and atrial natriuretic factor on neuronal and
      non-neuronal noradrenaline uptake in the central nervous system of the rat.
AB  - Binding sites of atrial natriuretic factor (ANF) and bradykinin (BDK) have been
      described in discrete areas of central nervous system of the rat. The interaction
      between ANF and BDK on noradrenaline (NA) uptake were studied in hypothalamus
      (Hyp) and medulla oblongata (MO). One hundred nM ANF in both regions and 100pM
      BDK in Hyp and 1nM BRD in MO increased total NA uptake. Subthreshold
      concentrations of ANF (1nM) reversed the effect of not modify the increase
      produced by 100nM ANF in both central regions. Effective concentrations of ANF
      and BDK did not induce additive effect in total 3H-NA uptake neither in Hyp nor
      in MO. Threshold concentrations of ANF and BDK increased only neuronal NA uptake
      in Hyp as well as MO. These results suggest an ANF-BDK interaction at the
      neuronal NA control mechanisms involved in the regulation of blood pressure,
      electrolytes and water balances, and neuroendocrine processes.

PMID- 7511426
TI  - [Cardiovascular function in man during experimental dives at 26 ATA (helium
      nitrogen-oxygen mixture)].
AB  - During two human experimental dives at 26 ATA (helium-nitrogen-oxygen gaz
      mixture; PIO2 = 400 mbar), the cardiac frequency (Fc) and radial arterial pulse
      were continuously recorded, at rest and during periods of maximal expiratory
      (Valsalva) or inspiratory (Muller) manoeuvres, used to increase or decrease the
      intrathoracic pressure, respectively. Cardiovascular variables were measured at 1
      and 26 ATA in resting individuals and during the maximal respiratory manoeuvres.
      Discontinuous measurement of arterial blood pressure using a sphygomanometer
      allowed to calculate the mean arterial pressure. The value of mean arterial
      pressure was maintained against the membrane of a radial pulse sensor. This
      procedure, proposed by Posey et al. (1969), gives a continuous approximation and
      recording of arterial blood pressure and its components. The present results did
      not show significant variation in the values of Fc nor systolic or diastolic
      blood pressures measured at rest or during Muller manoeuvres performed at 1ATA at
      the maximal depth. On the other hand, Valsalva manoeuvres performed at depth
      induced significant variations in circulatory variables compared to the
      normobaric response. The most important effect was an enlargement of differential
      pressure due to a marked decrease in the diastolic blood pressure. These
      observations are discussed in terms of enlarged sensitivity of the baroreflex
      arch under hyperbaric condition.

PMID- 7511427
TI  - An experimental model of hypoxia on isolated rat heart in recirculating system:
      study of fatty acid metabolism with an iodinated fatty acid.
AB  - An experimental model of hypoxia was developed on isolated rat heart to study the
      effects of hypoxia on cardiac performance and metabolism. Fatty acid (FA)
      metabolism was explored by external detection with a labelled FA,
      iodohexadecenoic acid (IHA). Hearts, after 30 min preperfusion in an open system,
      were transferred in a recirculating system for 40 min and perfused with oleate,
      glucose, lactate, pyruvate and IHA, either in normoxia (pO2 = 660 mmHg) or in
      hypoxia (pO2 = 220 mmHg). After 40 min hypoxic recirculation, oxygen uptake and
      dynamic parameters, except the heart rate, decreased respectively by 56% and 44%,
      and remained constant throughout the perfusion. Glucose utilization increased 2
      fold, endogenous glycogen fell by 50% and lactate + pyruvate production increased
      3 fold, showing a stimulation of glycolysis. Oleate uptake decreased by 28%,
      while triglycerides content remained higher. The ATP/ADP ratio decreased by 24%.
      Conversely to oleate, IHA uptake was not significantly modified, but its
      intracellular fate showed a higher radioactivity in all lipid fractions: polar
      lipids, diglycerides, free FAs and triglycerides. beta oxidation of IHA,
      evidenced by iodide production, decreased by 39%. The external detection of
      cardiac radioactivity allowed us to obtain time-activity curves that were
      analyzed with a 4-compartment mathematical model. The data evidenced an
      esterification ratio significantly higher in hypoxia. The metabolism of IHA as
      estimated by the intracellular analysis or, in a non-invasive way, by external
      detection, was similar to the metabolism of oleate. Thus, lipid metabolism, in
      hypoxia, can be explored by external detection with IHA.

PMID- 7511428
TI  - Blood coagulation factors changes during liver regeneration in rats.
AB  - Effects of partial hepatectomy on blood coagulation factors were investigated in
      rats. Analysis were performed 24, 48 and 72 hours after surgery. Howell's time
      was significantly higher after 24 and 48 h compared to the control value.
      Prothrombin time was significantly prolonged after 24 h. Partial thromboplastin
      time did not differ significantly in any time. FII values were significantly
      reduced after 24 and 48 h, but FV values only after 24 h. FVII showed significant
      decrease after 24 h, but significant increase at 48 h. FVIII and ATIII average
      values were significantly lower after 24, 48 and 72 h. Plasma fibrinogen
      increased. Significant differences were observed 48 and 72 h after surgery.
      Differences in normalization time of these coagulation factors are most probably
      the consequence of their synthesis in various cell types, regenerated at
      different periods after partial hepatectomy.

PMID- 7511429
TI  - The effects of clonidine, guanfacine and phenylephrine on the excitatory and
      inhibitory responses of the rat anococcygeus muscle.
AB  - The effects of clonidine, guanfacine and phenylephrine on twitch responses and
      the basal tone of the rat anococcygeus muscle were investigated. Clonidine (10(
      9)-3 x 10(-8) M) and guanfacine (10(-9)-10(-7) M) inhibited the twitch responses
      with the same potency, whereas phenylephrine (10(-9)-10(-7) M) was found
      ineffective. The inhibitory effect of clonidine and guanfacine was antagonized by
      yohimbine. Higher concentrations of clonidine and guanfacine increased the muscle
      tone and elicited inhibitory responses during field stimulation. Phenylephrine at
      concentrations greater than 10(-7) M also increased the muscle tone but induced
      biphasic responses. Clonidine (10(-7)-3 x 10(-5) M), guanfacine (3 x 10(-7)-3 x
      10(-5) M) and phenylephrine (3 x 10(-7)-10(-5) M) caused concentration-dependent
      increases in the basal tone. The order of potency of these agonists in increasing
      the basal tone was clonidine > guanfacine > phenylephrine. Both yohimbine (10(-8)
      10(-5) M) and prazosin (10(-9)-10(-7) M) antagonized these tonic contractions.
      Prazosin was found to be 39-, 122- and 83-fold more potent than yohimbine in
      antagonizing clonidine, guanfacine and phenylephrine-induced tonic contractions,
      respectively. Clonidine and guanfacine inhibited twitch responses through
      stimulation of presynaptic alpha-2 adrenoceptors. Postsynaptic alpha-1
      adrenoceptors seem responsible for the contractile effects of clonidine,
      guanfacine and phenylephrine in the rat anococcygeus muscle.

PMID- 7511430
TI  - [In vivo effects of 24R,25-dihydroxyvitamin D3 on kidney alkaline phosphatase and
      gamma-glutamyltransferase of hypophysectomized rats].
AB  - The effects of 24R, 25-dihydroxyvitamin D3 (24, 25 (OH)2 D3) on alkaline
      phosphatase (ALP), gamma-glutamyltransferase (GGT) and acid phosphatase (ACP)
      activities were investigated on renal cortex of hypophysectomized (Hx) rats. ALP
      activity was increased by +27, +56 and +60% as compared to controls respectively
      3, 6 and 12 h after intraperitoneal administration of the secosteroid (10
      pmoles/100 g body weight). Stimulations of GGT activity began only after 6 h
      (+30%) and 12 h (+ 46%). ACP activity was not modified. In vivo, the two
      enzymatic inductions in kidneys of Hx rats were higher and longer than those
      obtained in vitro.

PMID- 7511431
TI  - Rat gastrocnemius high and low frequency fatigue without metabolic impairment by
      31P NMR.
AB  - Metabolic status and intracellular pH were investigated using 31-P nuclear
      magnetic resonance spectroscopy during mechanical fatigue induced in rat
      gastrocnemius muscle in vivo by continuous stimulation either at low or high
      frequency. During high frequency stimulations, force decreased to low level (10%
      of initial in 3-6 min) while phosphocreatine declined abruptly to 28-30% of its
      initial level and pH fell to 6.36 in 45 seconds. Force then continued to fall but
      PCr and pH rose again to reach 80-85% of the initial phosphocreatine value and
      6.96 (pH) at the end of the stimulation period. The major feature of these
      results at high frequency was that the muscle could not generate force despite
      high energy stores and normal pH. During low frequency stimulation, force
      decreased in 9 min, to 10% of initial level. Phosphocreatine decreased abruptly
      to become undetectable while pH declined to 6.08 in 90 seconds. But later,
      phosphocreatine rose again to 35% and pH recovered to 6.84 while force continued
      to fall. Our results showed that intracellular pH and energy stores are not
      involved in the development and maintenance of mechanical fatigue.

PMID- 7511435
TI  - [Possibility of functional exploration of mastication from acoustic signals].
AB  - The chewing abnormalities are frequently evoked during odontological and medical
      examinations. Unfortunately, few means of investigation are available to
      appreciate the functional disorders. The aim of this paper was to assess
      masticatory parameters from observation and audiosignals of mastication with a
      simple analysis of records. In a first time, sixty five students (mean age = 20)
      applied the sugar test for the salivary capacity (dissolution time = 2 to 3
      minutes). Then the chewing movements were analysed with three types (I, II, III)
      of salt or sweet cookies. The total duration of activity was 29.8 and 28.2
      seconds respectively for the tests I and II, only 18.2 seconds for the test III.
      The number of cycles were 32.5, 28.1 and 19.2 mastications for respectively I, II
      and III tests. The later type (III) had a softer consistency than the formers.
      The duration Dc of masticatory cycles was constant for the same type of aliment.
      The values were between 0.70 for the test II and 0.90 second for the I and II
      ones. Signal analysis showed an important and rapid decrease of amplitude AS with
      an exponential-like pattern. The time constant appeared in relation with the
      softness. Thus, our method allows to characterize the pattern of mastication and
      could be used for appreciation of degrees in salivary and/or cranio-mandibular
      functional abnormalities.

PMID- 7511434
TI  - Gentamicin nephrotoxicity in rats is not modified by verapamil.
AB  - To assess whether calcium could be involved in the gentamicin-induced
      nephrotoxicity, we have studied the effect of the calcium channel blocker
      verapamil on renal function in rats intoxicated by gentamicin. Male Wistar rats
      were divided in three groups. In group I (n = 7) they were injected with
      gentamicin 100 mg/kg body wt/day s.c. for 5 days. In group II (n = 6), they
      received gentamicin and verapamil s.c. 2 mg/rat/day. In group III rats served as
      control. Plasma creatinine and creatinine clearance were daily measured. Rats
      treated with gentamicin showed a progressive increase in plasma creatinine and a
      drop in creatinine clearance. No differences between rats treated with gentamicin
      and those with gentamicin plus verapamil were observed. The urinary flow
      decreased after treatment with gentamicin, this decrease being more marked in
      rats treated with verapamil. No differences in daily urinary sodium and potassium
      excretion were found between intoxicated rats treated or not with verapamil. The
      present results show that, in rats, verapamil has no protective effect against
      the nephrotoxicity of gentamicin.

PMID- 7511432
TI  - [Comparison of hydroelectrolytic exchange characterized by calculation of
      saturable fluxes at three levels of the rat intestine].
AB  - Using the everted sac technique, which responded, as expected, to VIP by an
      increase of the secretion and to glucose by an increase of the absorption, we
      compared the water and electrolyte movements in the jejunum, ileum and colon in
      rats. Identical iso-osmolar test-solutions containing increasing NaCl
      concentrations, placed on the serosal and mucosal sides, allowed us to quantify
      fluxes in the absence of initial gradient. The measured net Na and Cl fluxes were
      dissociated into their two components, a passive flux from serosa to mucosa and a
      saturable flux from mucosa to serosa. The parameters of the saturable transport,
      calculated for each of the intestinal parts, showed the highest J max for the
      ileum (58.5 microEq.g-1.h-1 for Na and 52.8 microEq.g-1.h-1 for Cl) and the
      lowest Km for the colon that had the highest affinity for sodium and chloride (Km
      11.1 mM for Na and 7.8 mM for Cl). These data confirm the functional difference
      between the three intestinal parts, with an active absorption of Na and active
      secretion of Cl in the jejunum, an apparent coupled Na and Cl absorption in the
      ileum and an active absorption with high affinity for both Na and Cl in the
      colon.

PMID- 7511437
TI  - Cardioprotective effect of L-carnitine in rats submitted to permanent left
      coronary artery ligation.
AB  - Several studies have suggested that L-carnitine may limit the cellular
      alterations induced by myocardial hypoxia or ischemia. In the present study, rats
      were subjected to chronic treatment with L-carnitine (0, 25, 50 or 200 mg/kg/day
      i.p.) for 9 days prior to being submitted to permanent regional myocardial
      ischemia by left coronary artery ligation in situ. Following 48 hours of coronary
      occlusion, infarct size was measured using planimetry of transverse sections of
      the hearts, which had been stained with nitro-blue tetrazolium. Various
      functional and metabolic parameters have also been measured in isolated perfused
      hearts. Treatment with L-carnitine at 200 mg/kg/day i.p. for 9 days led to a
      significant reduction in infarct size and a better preservation of residual
      cardiac function. However, none of the metabolic parameters measured were
      modified. In conclusion, we suggest that the preservation of cardiac contractile
      function observed with L-carnitine pretreatment is secondary to carnitine-induced
      infarct size limitation.

PMID- 7511433
TI  - Ca(2+)-ATPase and Mg(2+)-ATPase activities distinct from alkaline phosphatase in
      rat jejunal brush-border membranes.
AB  - In rat jejunal brush-border membranes (BBM), ATP hydrolysis activity was
      specifically stimulated by CaCl2 and by MgCl2, allowing to identify Ca(2+)-ATPase
      and Mg(2+)-ATPase activities with a broad pH optimum near 8.0. Nonspecific ATPase
      activity (in the absence of cations) had a pH optimum above 9.5 as alkaline
      phosphatase. The effects of Ca2+ and Mg2+ concentrations on ATPase activity
      evidenced two apparent KA for each cation. At high concentrations, a similar
      affinity for both cations was recorded (KA: 0.35 mM). At low concentrations, the
      affinity for Mg2+ was greater than for Ca2+ (KA: 0.02 mM and 0.07 mM
      respectively). In an attempt to differentially solubilize alkaline phosphatase
      and ATPase activities, eleven different detergents were assayed. They more or
      less successfully released Ca(2+)-ATPase and Mg(2+)-ATPase activities from BBM
      but the more membranes were solubilized by a detergent, the more activities were
      lost, suggesting a close dependence on integration in BBM. As to alkaline
      phosphatase and nonspecific ATPase, they almost co-solubilized with Ca(2+)-ATPase
      and Mg(2+)-ATPase but their total activity was little affected. After treatment
      of BBM with phosphatidylinositol-specific phospholipase C (E.C. 3.1.4.10), 58% of
      alkaline phosphatase activity and 45% of nonspecific ATPase activity were
      released in the supernatant while Ca(2+)-ATPase and Mg(2+)-ATPase activities
      remained totally incorporated in BBM pellets. These last results definitively
      demonstrate that Ca(2+)-ATPase and Mg(2+)-ATPase activities are not
      manifestations of alkaline phosphatase, as earlier suggested, but rather result
      from the existence of one or several intrinsic membrane enzymes.

PMID- 7511438
TI  - Renal excretion of plasma soluble melanins by healthy human adults.
AB  - The soluble melanins of blood plasma form in vivo and in vitro from dopa,
      catecholamines, catechol, hydroquinone, homogentisic acid, 3-hydroxykynurenine, 3
      hydroxyanthranilic acid, p-aminophenol, p-phenylenediamine and other structurally
      related end(ex)ogenous compounds by oxidative polymerization. The mean quantity
      of natural melanins in normal plasma is 1.61 +/- 0.10 (standard deviation) mg/ml,
      (n = 20) and in uraemic plasma 2.72 +/- 0.38 mg/ml, (n = 16). The plasma melanins
      (approximately 3%), are associated with proteins (approximately 85%),
      mucoproteins (approximately 0.25%), lipids (approximately 0.4%), as soluble
      lipofuscins, and probably are associated with proteins without lipids as soluble
      melanoproteins. Fluorescence, UV-VIS and IR spectroscopies and the melanin
      isolation method show the presence of soluble melanins in the urine of healthy
      people. Soluble melanins can also be formed in vitro in the urine by oxidative
      polymerization of the precursors. In most of the urine samples we studied,
      melanins were present in larger amounts than the urinary proteins, indicating
      that the kidneys can selectively excrete the melanin components of the
      lipofuscins, and that the solubility of melanins does not depend upon combination
      with proteins. The quantities of purified melanins precipitated with 6 N HCl at
      110 degrees C during 72 h from urine samples collected during 24 h periods ranged
      from 0.1460 g to 3.7627 g (mean 1.1303 +/- 1.1739 g, n = 8) and the plasma
      clearance rates ranged from 0.06 ml/min to 1.56 ml/min (mean 0.48 +/- 0.48
      ml/min, n = 8). From the individual 24 h urine samples we obtained from 9 to 216
      mg/dl of precipitated melanins while the individual plasma samples contained from
      145 to 175 mg/dl.

PMID- 7511436
TI  - Changes in blood ammonia induced by a maximum effort in trained and untrained
      subjects.
AB  - Twelve healthy male volunteers, either trained or untrained, performed a maximal
      exercise on a cycloergometer. Venous blood samples were taken for analysis during
      the effort and the following recovery. Blood concentrations of lactate and
      ammonia, and plasmatic concentrations of alanine, glutamate and glutamine were
      measured. At the beginning on the effort, ammonia decreased by 32% (P < 0.01) in
      comparison with its mean level at rest; at 77% and 78% of maximum load there was
      a steeper ascent of blood ammonia and lactate vs load curve. There was a high
      correlation (P < 0.001) between ammonia and lactate during exercise. At the end
      of the effort, these two variables had significantly increased in comparison with
      their values at rest (P < 0.01 for ammonia and P < 0.001 for lactate), but they
      did not correlate with VO2max. The negative correlation existing between ammonia
      and VO2max at the beginning of the recovery period may imply that muscle NH3
      release is inversely proportional to the subject's sports training level, this
      relation being less evident when blood lactate vs VO2max correlation was
      considered. Increase in blood glutamate level was greater in trained subjects (P
      < 0.05). This finding suggests that ammonia elimination is favoured by physical
      training. In conclusion, ammonia measurements during exercise provide a valuable
      information about muscle cell oxidative capacity.

PMID- 7511439
TI  - Morphogenetic and growth related changes in lipids of Drosophila ananassae
      (Doleschall).
AB  - The lipid component of Drosophila ananassae have been identified qualitatively.
      Neutral and phospholipid fractions are specific for pupal, larval or adult
      extracts. Some of these lipid components are identical with those obtained from
      the temperate D. melanogaster and other species. This demonstrates biochemical
      convergence between geographically isolated species groups.

PMID- 7511440
TI  - Transcriptional regulation and chromatin structure of the human CD34 gene
      promoter region.
AB  - The human CD34 surface antigen is selectively expressed on stem/progenitor cells
      within the hematopoietic system. Because CD34 expression is tightly linked to the
      immature status of hematopoietic cells, with expression being rapidly lost as
      hematopoietic cells mature and differentiate, an examination of its regulation
      may provide important insights into the molecular control of blood cell
      development. A comparison of the CD34 nuclear transcription rate in CD34+ and
      CD34- cells indicated that the CD34 gene is transcriptionally regulated in
      hematopoietic cell lines. In a previous report, we had identified two major
      clusters of CD34 transcription initiation sites by 5' RACE (rapid amplification
      of cDNA ends) analysis. In transient transfection experiments, we now demonstrate
      the ability of sequences encompassing each of these clusters to function as
      promoters of transcription in CD34+ cells. These promoters functioned at
      equivalent levels in CD34+ and CD34- cells, and the addition of 5' flanking
      sequences, extending as far as 3.7 kb upstream, to the core promoters did not
      differentially modify the level of expression in CD34+ versus the CD34- cell
      lines. An examination of DNase I hypersensitivity sites within an 18-kb segment
      of DNA, extending 9 kb either side of the proximal promoter, showed six sites
      that were primarily associated with CD34- expressing cells. Taken together, these
      data indicate that the CD34 promoter sequences alone do not confer tissue-or
      stage-specific expression. Appropriate transcriptional regulation of the CD34
      gene must be controlled by chromatin structure, as identified by DNase I
      hypersensitivity, and/or by other tissue- and stage-specific elements present
      outside of the promoter region.

PMID- 7511441
TI  - Inverse expression of bcl-2 protein and Fas antigen in lymphoblasts in peripheral
      lymph nodes and activated peripheral blood T and B lymphocytes.
AB  - To examine the regulatory mechanism of apoptosis in lymphoid cells, expression of
      both bcl-2 protein and Fas antigen was investigated in reactive lymph nodes, in
      resting lymphocytes from peripheral blood (PBLs), and in PBLs stimulated with
      pokeweed mitogen, interleukin-4 (IL-4) + anti-IgM antibody, IL-2 + anti-CD3
      antibody, phytohemagglutinin + phorbol myristate acetate using
      immunohistochemistry and flow cytometry. Germinal center cells expressed a large
      amount of Fas antigen, which is associated with the induction of apoptosis in
      lymphoid cell lines, in contrast to the lack of bcl-2 protein as an apoptosis
      inhibitor. On the other hand, mantle zone lymphocytes expressed a high level of
      bcl-2 protein and less Fas antigen. This inverse expression of bcl-2 protein and
      Fas antigen was also shown in activated T and B lymphocytes from peripheral
      blood. These lymphoblasts fell into apoptosis dose-dependently in the presence of
      anti-Fas monoclonal antibody, but resting lymphocytes that expressed both bcl-2
      protein and Fas antigen did not undergo apoptosis. These findings suggest that
      bcl-2 expression prevents the apoptosis of lymphoid cells induced by the Fas
      antigen-dependent mechanism and that apoptosis of lymphocytes is exquisitely
      controlled, at least in part, by regulation of the bcl-2 and Fas genes.

PMID- 7511442
TI  - Retinoic acid and granulocyte colony-stimulating factor synergistically induce
      leukocyte alkaline phosphatase in acute promyelocytic leukemia cells.
AB  - In this report we show a strong synergistic interaction between granulocyte
      colony-stimulating factor (G-CSF) and all-trans retinoic acid (ATRA) on the
      expression of leukocyte alkaline phosphatase (LAP) in freshly isolated acute
      promyelocytic leukemia (APL) blasts as well as in NB40 and HL-60 cell lines. The
      strong synergism observed in these cell types was not evident in two acute
      leukemia cell lines (K562 and GF-D8), in normal granulocytes, and in monocytes.
      In freshly isolated leukocytes derived from chronic myelogenous leukemia (CML),
      in the stable phase of the disease, a weaker interaction between ATRA and G-CSF
      was documented. The cross-talk between the cytokine and the retinoid was studied
      in detail in NB4, an immortalized APL leukemia cell line, retaining the 15-17
      chromosomal translocation involving the retinoic acid receptor type alpha. The
      treatment of NB4 cells with G-CSF alone or ATRA alone leads to no increase and to
      minor induction in LAP activity, respectively. If the cells are treated with the
      two compounds simultaneously, a dramatic elevation of LAP is observed after 4
      days. The synergism between G-CSF and ATRA is evident at concentrations of the
      retinoid between 10(-7) and 10(-5) mol/L and at concentrations of the cytokine
      between 1 and 10 ng/mL. The simultaneous presence of the two compounds is
      necessary to obtain maximal increase of LAP activity and the effect is cell
      density-dependent. Synergism is specific for G-CSF, and it is not observed with
      other cytokines and functional inducers of the granulocyte. The augmentation of
      LAP activity is the consequence of an increased transcriptional rate of the
      liver/bone/kidney-type (L/B/K-type) alkaline phosphatase gene, as determined by
      Northern blotting and nuclear run-on analysis using specific cDNA probes. Only
      one of the two possible alternatively spliced forms of L/B/K-type alkaline
      phosphatase transcript is detected in NB4 cells after stimulation with G-CSF and
      ATRA. This mRNA form, which is the one observed in normal polymorphonuclear
      leukocytes, contains the most upstream leader exon. In NB4 cells, ATRA induces G
      CSF, alpha, and beta retinoic acid receptor transcripts, whereas G-CSF has minor
      effects on the expression of these mRNAs.

PMID- 7511443
TI  - Effect of priming polymorphonuclear leukocytes with cytokines (granulocyte
      macrophage colony-stimulating factor [GM-CSF] and G-CSF) on the host resistance
      to Streptococcus pneumoniae in chinchillas infected with influenza A virus.
AB  - Patients infected with influenza A virus (IAV) are at increased risk for
      bacterial superinfections, and this occurs in association with depressed
      polymorphonuclear leukocyte (PMNL) function. Recently, we reported that in vitro
      exposure of human PMNL to granulocyte-macrophage colony-stimulating factor (GM
      CSF) reverses IAV-induced cell dysfunction. The present study used an established
      animal model of IAV infection to examine whether G-CSF and/or GM-CSF can overcome
      IAV-induced PMNL dysfunction and thereby prevent secondary infections.
      Preliminary studies determined a dosing schedule of these cytokines that caused
      significant priming of chinchilla PMNL. In subsequent studies, animals were
      inoculated intranasally with IAV (day 1) followed 3 days later by Streptococcus
      pneumoniae, and administered daily intraperitoneal injections with a cytokine or
      placebo on days 3 through 9. Animals had blood obtained on multiple occasions for
      PMNL studies, and were followed-up for evidence of pneumococcal disease. Both
      cytokines caused significant priming of the PMNL chemiluminescence response and
      this was associated with reversal of the IAV-induced PMNL dysfunction. However,
      neither cytokine decreased the incidence of pneumococcal disease.

PMID- 7511444
TI  - Hepatitis C virus infection is a risk factor for liver failure from veno
      occlusive disease after bone marrow transplantation.
AB  - The contribution of hepatitis C virus (HCV) infection to liver disease after bone
      marrow transplantation (BMT) was retrospectively evaluated in 61 patients treated
      with BMT. HCV genome, as well as antibodies to HCV, was analyzed in sera
      collected before and serially after BMT. Six patients had been infected with HCV
      before BMT and three patients acquired the infection during or shortly after BMT.
      All patients infected before BMT died within 10 weeks after transplantation. Five
      of these six patients (83%) died of veno-occlusive disease (VOD), compared with
      nine of 52 patients (17%) not infected with HCV (P < .005). Risk factors for VOD
      other than HCV were not more prevalent in these patients compared with uninfected
      patients. Parallel to the development of VOD, replication of HCV increased, as
      demonstrated by rising concentrations of viral RNA in serum. HCV infection
      acquired during or after BMT caused only mild acute hepatitis C, which progressed
      to chronic hepatitis C in one patient surviving 10 years after BMT. These data
      suggest that patients with liver disease caused by HCV infection are at high risk
      of developing lethal VOD after BMT.

PMID- 7511445
TI  - Mutagenic activity and chemical analysis of airborne particulates collected in
      Pisa (Italy).

PMID- 7511446
TI  - [Lipids and acute lung failure].

PMID- 7511447
TI  - [Risks of infusion of colloidal solutions].

PMID- 7511448
TI  - Modulation of pulmonary vascular resistance and edema formation by short-term
      infusion of a 10% fish oil emulsion.
AB  - BACKGROUND: The aim of this study was to investigate whether the pulmonary
      response to inflammatory stimulation, resulting in increased vascular resistance
      and permeability, could be attenuated by short-term infusion of triglycerides
      containing omega-3 fatty acids. With the concept of altering the composition of
      membrane phospholipids in such a manner that stimulation resulted in the release
      of less vasoconstrictive and permeability-enhancing metabolites of
      eicosapentaenoic acid instead of those of arachidonic acid (AA), the parenteral
      application of a lipid emulsion prepared from fish oil (Omegavenos) was tested in
      comparison with a soy oil preparation (Lipovenos). METHODS: Isolated lungs from
      anesthetized rabbits were ventilated and recirculatingly perfused (200 ml/min)
      with 200 ml cell-free buffer solution to which either 2 ml saline (controls, n =
      6), 2 ml Lipovenos 10% (n = 6) or 2 ml Omegavenos 10% (n = 6) were added. To
      study the possible metabolic alterations in states of an enhanced AA turnover,
      lungs of each group were stimulated with smaller doses of A23187 (10(-8) M)
      during the 180-min lipid perfusion period, followed by a 10 times higher calcium
      ionophore A23187 (10(-7) M) challenge after washing out the lipids by exchange of
      perfusion fluid. Pulmonary artery pressure (PAP) and the lung weight gain
      indicating edema formation were monitored, and eicosanoids were analyzed in
      samples of the perfusate. RESULTS: Upon A23187 injection lung weight gain and PAP
      increase were significantly reduced (50%) in Omegavenos-perfused lungs in
      comparison with controls and Lipovenos treatment. The vascular reactions were
      accompanied by a shifting from LTC4 to LTC5 during and after Omegavenos
      perfusion. CONCLUSION: The data demonstrate that omega-3 fatty acids seem to be
      incorporated into the phospholipid pool of the pulmonary tissue, even after short
      term infusion (3 h) resulting in an attenuated pressure reaction and edema
      formation due to an altered spectrum of metabolites in the case of inflammatory
      stimulation.

PMID- 7511449
TI  - [Severe dextran-induced anaphylactic/anaphylactoid reaction despite preventive
      hapten administration].
AB  - Dextran-60 is widely used as a colloid volume substitute and for
      thromboprophylaxis. In order to avoid the most dangerous complication associated
      with dextran, the dextran-induced anaphylactic/anaphylactoid reaction (DIAR),
      hapten dextran is infused before starting the first application of dextran. We
      report of a 60-year-old man with multiple trauma, who received a dextran infusion
      for thromboprophylaxis because of high risk for thrombosis due to a severe
      thrombocytosis developing in the late postoperative period. Despite prophylaxis
      with monovalent hapten dextran, an anaphylactic reaction occurred. Although a
      serum sample drawn prior to the reaction is lacking, the causal relationship to
      dextran can be classified as likely, due to the close time relationship to the
      dextran-60 infusion. In addition, there were high titers of dextran-reactive
      antibodies in the blood drawn immediately after the reaction occurred. It is
      concluded that even after correct application of monovalent hapten dextran,
      dextran infusions carry the risk of severe anaphylactic reactions. They should
      therefore only be administered if clinical observation of the patient and the
      possibility of resuscitation are guaranteed.

PMID- 7511450
TI  - Fixation and central visual field after perifoveal krypton laser treatment of
      subfoveal neovascularizations.
AB  - In contrast to focal laser treatment of large subfoveal neovascular membranes,
      perifoveal laser treatment sparing the central avascular zone can partially
      retain central macular function in some cases. The anatomical and functional
      outcome of this technique was analysed in 26 patients with large subfoveal
      neovascular membranes (0.6 to 3.0 disc diameter) secondary to age-related macular
      degeneration (24 cases) or presumed ocular histoplasmosis syndrome (two cases).
      Patients were followed for six to 39 months. Out of 26 patients 21 had a stable
      dry scar at the last follow-up examination. Central fixation was retained
      postoperatively in nine out of 13 patients with central fixation prior to laser
      treatment. Visual acuity was maintained or improved in 19 out of 26 treated eyes.
      Statpack analysis (Humphrey Field Analyser) of the long-term results of patients
      with central fixation indicated an increase in the depth of their relative
      central scotoma not only immediately after laser treatment but also in the first
      and second postoperative years. This increasing depth of central scotoma
      subsequently led to a shift of central fixation to a paracentral area in four out
      of nine patients six to nine months after treatment. Indocyanine-green
      angiography showed remaining subfoveal choroidal vasculature corresponding to the
      area of central fixation, as found in fundus microperimetry by scanning laser
      ophthalmoscope. Perifoveal laser treatment seems to be effective in maintaining
      some initial macular function for a limited time in selected patients suffering
      from subfoveal neovascular membranes.

PMID- 7511451
TI  - Treatment of extended lid lacerations with dextranomer beads.
AB  - The Author demonstrates the use of dextranomer beads (Debrisan) in an extended
      upper and lower lid laceration. He found the dextranomer beads helpful in the
      treatment of lid lacerations. The mechanism of action of dextranomer beads is
      described as well. He is not aware of any publications about the use of
      dextranomer beads in ophthalmology.

PMID- 7511452
TI  - Aqueous humour lactic acid and proteins in eyes with iris neovascularization.
AB  - The content of lactic acid and proteins in the aqueous humour of eyes with
      neovascularization of the iris (NVI) of various etiology was determined. The
      results were analysed for any possible correlation with the angiogenesis observed
      in such eyes. Aqueous humour from patients with immature senile cataracts served
      as the control. The total protein concentration in cases of NVI (mean +/- SD,
      345.7 +/- 161.0 mg/dl; n = 15) was significantly raised (P < 0.001) as compared
      with the control values (mean +/- SD, 30.91 +/- 14.95 mg/dl; n = 12). On the
      other hand, the concentration of lactic acid in cases of NVI (mean +/- SD, 45.97
      +/- 15.5 mg/dl; n = 13) was significantly lower (P < 0.01) as compared with the
      controls (mean +/- SD, 65.86 +/- 10.9 mg/dl; n = 8). These findings show that
      angiogenesis is not associated with a raised level of lactic acid in the aqueous
      humour, whereas the elevated protein values are suggestive of a breakdown of the
      blood-aqueous barrier.

PMID- 7511453
TI  - Improving the sensitivity of the sequence profile method.
AB  - The sequence profile method (Gribskov M, McLachlan AD, Eisenberg D, 1987, Proc
      Natl Acad Sci USA 84:4355-4358) is a powerful tool to detect distant
      relationships between amino acid sequences. A profile is a table of position
      specific scores and gap penalties, providing a generalized description of a
      protein motif, which can be used for sequence alignments and database searches
      instead of an individual sequence. A sequence profile is derived from a multiple
      sequence alignment. We have found 2 ways to improve the sensitivity of sequence
      profiles: (1) Sequence weights: Usage of individual weights for each sequence
      avoids bias toward closely related sequences. These weights are automatically
      assigned based on the distance of the sequences using a published procedure
      (Sibbald PR, Argos P, 1990, J Mol Biol 216:813-818). (2) Amino acid substitution
      table: In addition to the alignment, the construction of a profile also needs an
      amino acid substitution table. We have found that in some cases a new table, the
      BLOSUM45 table (Henikoff S, Henikoff JG, 1992, Proc Natl Acad Sci USA 89:10915
      10919), is more sensitive than the original Dayhoff table or the modified Dayhoff
      table used in the current implementation. Profiles derived by the improved method
      are more sensitive and selective in a number of cases where previous methods have
      failed to completely separate true members from false positives.

PMID- 7511455
TI  - Protein-tyrosine kinases: potential targets for anticancer drug development.
AB  - Protein-tyrosine kinases (PTKs) were originally discovered over a decade ago as
      the dominant transforming components of certain tumor viruses. Since then these
      enzymes have become recognized as important intracellular mediators of a variety
      of mitogenic signaling pathways, including those associated with several growth
      factor receptors. The strong correlation of aberrant or over-expressed PTKs with
      a number of proliferative diseases has raised the possibility that PTK inhibitors
      may afford new approaches toward anticancer therapeutics. To address this
      possibility, potent and specific PTK inhibitors are needed both as
      pharmacological probes to study PTK-dependent signaling and as potential
      antiproliferative agents in their own right. De novo design of PTK inhibitors is
      hampered by a lack of three dimensional information regarding PTKs or the
      interaction of inhibitors with the enzymes. Motifs for the design of new
      inhibitors are therefore frequently derived by modification of structural them
      identified in natural-product screens. Exemplary of this process is the
      Laboratory of Medicinal Chemistry's program to develop PTK inhibitors based on
      pharmacophores present in three natural-product PTK inhibitors: lavendustin A,
      erbstatin and piceatannol. As summarized in this report, such efforts have led to
      new inhibitors with increased potency and interkinase selectivity. Whether PTK
      inhibitors will ultimately prove to be useful as antiproliferative therapeutics
      remains an open question whose answer will be heavily reliant on a cooperative
      partnership among natural-product and medicinal chemists, pharmacologists and
      clinicians.

PMID- 7511454
TI  - A two-domain structure for the two subunits of NAD(P)H:quinone acceptor
      oxidoreductase.
AB  - NAD(P)H:quinone acceptor oxidoreductase (EC 1.6.99.2) (DT-diaphorase) is a FAD
      containing reductase that catalyzes a unique 2-electron reduction of quinones. It
      consists of 2 identical subunits. In this study, it was found that the carboxyl
      terminal portion of the 2 subunits can be cleaved by various proteases, whereas
      the amino-terminal portion cannot. It was also found that proteolytic digestion
      of the enzyme can be blocked by the prosthetic group FAD, substrates NAD(P)H and
      menadione, and inhibitors dicoumarol and phenindione. Interestingly, chrysin and
      Cibacron blue, 2 additional inhibitors, cannot protect the enzyme from
      proteolytic digestion. The results obtained from this study indicate that the
      subunit of the quinone reductase has a 2-domain structure, i.e., an amino
      terminal compact domain and a carboxyl-terminal flexible domain. A structural
      model of the quinone reductase is generated based on results obtained from amino
      terminal and carboxyl-terminal protein sequence analyses and electrospray mass
      spectral analyses of hydrolytic products of the enzyme generated by trypsin,
      chymotrypsin, and Staphylococcus aureus protease. Furthermore, based on the data,
      it is suggested that the binding of substrates involves an interaction between 2
      structural domains.

PMID- 7511456
TI  - Efficient isolation of human CD34 positive hemopoietic progenitor cells by immune
      panninga.
AB  - In this study we have assessed the use of soybean agglutinin (SBA) and CD34
      microcellector devices for the selection of CD34 positive hemopoietic progenitor
      cells. Burst forming unit-erythroid (BFU-E), colony forming unit
      granulocyte/macrophage (CFU-GM) and the recently developed multipotential human
      colony forming unit-type A (CFU-A) clonogenic assays were used to measure
      progenitor numbers in the starting mononuclear cell (MNC), the SBA negative, the
      nonadherent CD34 negative and the adherent CD34 positive fractions during
      panning. CFU-A progenitors were present at a relatively high incidence in the MNC
      fraction (220 per 10(5) MNC) and were enriched 15-fold in the adherent CD34
      positive fraction. This progenitor incidence and enrichment were similar to those
      of CFU-GM and BFU-E. The mean recovery for CD34 positive cells was 2.3 x 10(6)
      cells per marrow aspirate. Analyses by flow cytometry demonstrated that 1-5% of
      input MNC were CD34 positive, that the purity of the CD34 fraction was
      approximately 80% and that the calculated recovery for CD34 positive cells was
      61%. Recoveries for CFU-GM, BFU-E and CFU-A were between 18 and 40%. CFU-A
      progenitors were found exclusively in the adherent CD34 positive fraction,
      whereas a significant proportion of both CFU-GM and BFU-E were present in the
      nonadherent CD34 negative fraction. We propose that the Applied Immune Sciences
      (AIS) flasks preferentially bind the cells which express CD34 most strongly and
      that this is reflected in the finding of primitive CFU-A only in the CD34
      positive fraction, with lineage-restricted progenitors found in both CD34
      positive and negative fractions. This hypothesis is strengthened by data on long
      term bone marrow cultures in which the CD34 positive fraction is better able to
      maintain output of CFU-GM compared with the CD34 negative fraction. In
      conclusion, relatively pure populations of CD34 positive cells may be rapidly and
      efficiently isolated from bone marrow samples with good recovery. The isolated
      cells show enhanced colony forming capacity in standard clonogenic assays and in
      the multipotential CFU-A assay.

PMID- 7511457
TI  - CD34 selection for purging in multiple myeloma and analysis of CD34+ B cell
      precursors.
AB  - Selection of CD34+ hematopoietic progenitor cells from autografts may be
      performed in multiple myeloma (MM) to minimize contamination with tumor cells.
      This approach is based on the assumption that the malignant cells do not express
      the CD34 antigen. Therefore, we first compared the CD34+/CD10+ and CD34+/CD19+
      subpopulations from bone marrow (BM) and peripheral blood (PB) of fourteen MM
      patients and five normal controls. No difference between the respective early B
      cell subsets of both groups could be observed. Using tricolor flow cytometry, the
      CD19 expression on CD34+/CD10+ cells in BM was found to increase continuously
      from CD19- to CD19dim. In contrast, circulating CD34+/CD10+ cells did not
      coexpress the CD19 antigen. This population may contain myeloid progenitor cells
      or bipotential progenitor cells of the myeloid and lymphoid lineage as suggested
      by data obtained with fetal liver cells. Further functional studies are required.
      Enrichment of CD34+ cells with immunomagnetic beads was performed from BM of
      three MM patients and four normal donors. The CD34+ cells were selected with the
      HPCA-1 antibody and detached from the beads with chymopapain. Compared with the
      starting cell preparation, a 3.97 +/- 0.48 log (mean +/- SE) reduction of plasma
      cells could be achieved after CD34 selection. On morphological examination, 84%
      +/- 4% of the cells in the CD34+ fraction (MM) were immature blasts. The plating
      efficiency for hematopoietic colony forming cells was 9.7% +/- 2.8% in the CD34
      selected fraction of the MM group, reflecting a 51-fold increase as compared with
      the starting population.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511458
TI  - Haemophilus influenzae: the efficiency of reporting invasive disease in England
      and Wales.
AB  - This study compares the efficiency of a special regional survey with routine
      laboratory reporting to measure the incidence of invasive disease caused by
      Haemophilus influenzae before routine immunisation against type b strains was
      introduced. Incomplete reporting does not prevent the monitoring of trends, but
      it becomes important if the level of underreporting changes with time. This study
      illustrates the importance of assessing the quality of surveillance data before
      using them to inform policy or evaluate intervention. Underreporting to the
      regional survey was found to be 17% and underreporting to the Public Health
      Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC) was
      24%. In response to this study a system has been set up to send reference
      laboratories a weekly list of reports to CDSC. Manual cross checking helps to
      complete the ascertainment of cases. All isolates of H. influenzae from cases of
      invasive disease should be sent to the reference laboratories for serotyping as
      well as being reported to CDSC.

PMID- 7511459
TI  - Use of vaccines and antibiotic prophylaxis in contacts and cases of Haemophilus
      influenzae type b (Hib) disease.

PMID- 7511460
TI  - Hib immunisation catch up programme in North East Thames.

PMID- 7511461
TI  - 'COVER' (cover of vaccination evaluated rapidly): 28.

PMID- 7511462
TI  - Cryptosporidiosis associated with a swimming pool complex.
AB  - Twelve children and one adult in Gloucestershire fell ill with cryptosporidiosis
      in March 1992. Ten cases lived in or near a particular Cotswold town. Eight of
      these had visited a swimming pool within 24 hours of a suspected faecal accident,
      and two may have been secondary cases. Of the three cases who lived elsewhere,
      one was probably unrelated to the outbreak, one had visited the pool, and one was
      a contact of a boy who may have been the source of the outbreak.

PMID- 7511463
TI  - Effect of the 1993 European AIDS case definition in the United Kingdom.

PMID- 7511465
TI  - A study of men who have sex with men and who were recently infected with HIV.

PMID- 7511464
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7511466
TI  - Epidemic methicillin resistant Staphylococcus aureus in 1993.

PMID- 7511467
TI  - Effects of in utero drug exposure on children's development. Review and
      recommendations.
AB  - Effects of in utero drug exposure on pregnancy outcome, infant development, and
      preschool functioning are reviewed. Six possible mechanisms underlying possible
      negative outcomes seen in children exposed to drugs in utero are considered.
      Recommendations and opportunities for future research focus on process-oriented
      assessments, methodological and procedural issues, research design, and
      interventions.

PMID- 7511468
TI  - Alveolar CD8+CD57+ lymphocytes in human immunodeficiency virus infection produce
      an inhibitor of cytotoxic functions.
AB  - We investigated the CD8+CD57+ alveolar cell functions and their immunoregulatory
      role in lungs from HIV-seropositive patients with the clinical presentation of
      lymphocytic alveolitis at different stages of human immunodeficiency virus (HIV)
      disease. We previously reported, at Stage IV of HIV infection, an expansion of
      CD8+CD57+ alveolar lymphocytes mirroring the decline of local anti-HIV cytotoxic
      T-lymphocyte (CTL) responses, and demonstrated that sorted CD8+CD57+ alveolar
      lymphocytes inhibited the effector phase of these HIV-specific CTL. In the
      present study, we show that the expansion of CD8+CD57+ alveolar T cells can also
      be detected at stages II and III of HIV disease, although at a lower degree than
      observed at Stage IV of HIV infection. When sorted, these CD8+CD57+ alveolar
      lymphocytes block effector killer cells such as allospecific CTL, natural killer
      (NK), and lymphokine-activated killer (LAK) cells. The mechanism of action of
      these inhibitory T-lymphocytes has been further studied and we demonstrated that:
      (1) cell-to-cell contact between inhibitor and killer is not required, (2)
      nonstimulated alveolar CD8+CD57+lymphocytes but not CD57- lymphocytes
      spontaneously release a solube inhibitor of cytolytic functions (ICF). This
      inhibitory activity of alveolar CD8+CD57+ cells is mediated by a glycosylated
      protein which is distinct from tumor necrosis factor-alpha (TNF alpha), TNF beta,
      transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, interferon alpha (IFN
      alpha), interferon gamma (IFN gamma), and prostaglandins. The release of such an
      inhibitor of killer cell functions by CD8+CD57+ lymphocytes in the lungs, which
      are an important interface between the sterile body and the antigen-laden
      environment, may play a role in the local control of cell immunity.

PMID- 7511471
TI  - Unmasking MASCC. Multinational Association of Supportive Care in Cancer.

PMID- 7511469
TI  - DNA puff C4 of Bradysia hygida (Diptera: Sciaridae) contains genes unequally
      amplified and differentially expressed during development.
AB  - We report here the isolation and characterization of a 2.3 kb genomic EcoRI
      fragment that co-localizes in the DNA puff C4 of Bradysia hygida with a 4 kb
      EcoRI fragment previously characterized as containing part of a gene amplified
      and expressed in the salivary gland at the time when puff C4 expands.
      Verification of the relative amount of DNA complementary to these two genomic
      fragments shows that they are unequally amplified in the salivary gland. The
      fragment containing part of the gene expressed when puff C4 expands amplifies
      about eight times more than the 2.3 kb fragment. This 2.3 kb fragment also
      carries sequences complementary to RNA species present in the gland in a period
      when puff C4 has already receded. Based on these data we discuss the nature of
      the DNA puff and the possible way in which amplification is occurring at these
      sites.

PMID- 7511472
TI  - Endoscopic laser therapy in the tracheobronchial system.
AB  - Their physical properties make lasers ideal instruments for endoscopic surgical
      procedures in the narrow tracheobronchial system. By the thermal effects of the
      Nd-YAG laser, pathological benign and, especially, malignant lesions can be
      destroyed under direct vision. Working without contact with the tissue, sparing
      the risk of bleeding and further mechanical obstruction the laser has replaced
      mechanical and electrical devices and cryoprobes in interventional bronchoscopy
      to a large extent. Thus many patients with benign lesions can be spared the risk
      of major thoracic surgery of the large airways. To patients suffering from
      tumours of the central airways the chance of long-term palliation can be given by
      resolution of life-threatening complications. Furthermore, by photodynamic laser
      therapy after application of haematoporphyrin derivatives some patients may even
      be cured.

PMID- 7511473
TI  - Vapreotide, a new somatostatin analogue in the palliative management of
      obstructive ileus in advanced cancer.
AB  - Obstructive ileus is not common, but is a very distressing syndrome in a
      palliative care unit. The case of a 86-year-old woman with obstructive ileus due
      to advanced pancreatic cancer is presented. Successful management was made
      possible by a new somatostatin analogue (Vapreotide), administered i.m. at weekly
      intervals. Vapreotide was found to reduce nausea and vomiting considerably, by
      inhibiting the release and action of gastrointestinal hormones and the secretory
      and motor functions of stomach and intestines. The role of somatostatin analogues
      in the management of obstructive ileus in advanced cancer is discussed.

PMID- 7511470
TI  - Fractionation of human H1 subtypes and characterization of a subtype-specific
      antibody exhibiting non-uniform nuclear staining.
AB  - Four histone H1 subtypes and H1(0) were fractionated from human placental nuclei
      and purified to homogeneity by a combination of Bio-Rex 70 chromatography and
      reverse-phase high-performance liquid chromatography (RP-HPLC). Polyclonal
      antibodies were generated in rabbits against one of these subtypes designated H1
      3. Antibodies reacted only against this subtype in enzyme-linked immunosorbent
      assays and Western assays; subtype specificity was documented further by Western
      blotting of cell and nuclear extracts. They crossreacted with monkey H1, but not
      with H1 from other vertebrates tested. The epitope(s) recognized were mapped by
      immunoblotting against peptides prepared by cleavage with N-bromosuccinimide
      (NBS) and alpha-chymotrypsin; it includes the variant amino-terminal tail of the
      protein as well as a portion of the globular domain. The antibody stains mitotic
      chromosomes weakly but uniformly and, unlike antibodies that recognize total H1
      which show uniform nuclear staining after indirect immunofluorescence
      localization, anti-H1-3 exhibits preferential labelling of the nuclear periphery.
      This non-uniform staining suggests compartmentalization of this subtype which may
      have functional significance with respect to differential chromatin condensation.

PMID- 7511474
TI  - Cancer pain and supportive care.

PMID- 7511475
TI  - Undertreatment of cancer pain: barriers and remedies.
AB  - Over 70% of patients with cancer have moderate to severe pain during their
      illness and many fear pain more than death itself. There is consensus among
      experts that most patients can be well-palliated using knowledge, medications,
      and techniques that are readily accessible. Despite this, only a small proportion
      of patients with cancer pain receive adequate analgesia. Some of the barriers
      that interfere with the delivery of appropriate analgesia are patient-related,
      while others involve health-care providers. Patients frequently do not
      communicate the intensity of their pain to care-givers and are often hesitant to
      take opiates. Health-care providers receive scant teaching on cancer pain, have
      little awareness of pain intensity in their patients, and may be overly concerned
      about opiate toxicities. They lack appropriate role models in academic
      institutions and may be concerned about the potential for investigation by law
      enforcement agencies. These obstacles can be largely overcome by (a) emphasizing
      the importance of pain control in cancer patients, (b) considering the etiology
      of pain in each patient, (c) weighing the full range of available therapeutic
      options, (d) ensuring that "user-friendly" opiate-equivalence information is
      available, (e) using pain assessment tools routinely and recording pain intensity
      scores in the medical record, and by (f) not being easily dissuaded from
      providing adequate doses of opiates for pain relief. The rationale for and
      current efforts in each of these areas are discussed in this review.

PMID- 7511476
TI  - Bacterium-host cell interactions in Monterey.

PMID- 7511477
TI  - Yersinia enterocolitica lipopolysaccharide: genetics and virulence.
AB  - The O side chain (O antigen) of the lipopolysaccharide of Yersinia enterocolitica
      serotype O:3 has been shown to be a virulence factor. The genes directing the
      biosynthesis of the O antigen have been cloned, sequenced and characterized. Like
      the expression of most of the virulence factors of Y. enterocolitica, O-antigen
      expression is temperature regulated.

PMID- 7511478
TI  - SITEVIDEO: a computer system for functional site analysis and recognition.
      Investigation of the human splice sites.
AB  - We developed the computer system SITEVIDEO for analysis and recognition of the
      functional sites in DNA and RNA molecules. It reveals contextual features
      essential for site function and thus enable the user to design efficient methods
      for recognition of the functional sites. We mainly considered only quantitative
      characteristics reflecting the uneven distribution of oligonucleotides in the
      sequences of functional sites of interest. The approach suggested makes use of
      available information about the hierarchical organization of the functional
      sites, and ensures highly precise prediction of the sites. The present analysis
      is concerned with the human donor and acceptor splice sites. A method for
      recognizing these sites in the sequences with an accuracy of approximately 90%
      was developed.

PMID- 7511479
TI  - DCSE, an interactive tool for sequence alignment and secondary structure
      research.
AB  - DCSE provides a user-friendly package for the creation and editing of sequence
      alignments. The program runs on different platforms, including microcomputers and
      workstations. Apart from available hardware, the program is not limited in the
      size of the alignment it can handle. It deviates more from classical text editors
      than other available sequence editors because it uses a different approach
      towards editing. It shifts characters or entire blocks of aligned characters,
      rather than inserting or deleting gaps in the sequences. Alignment of a new
      sequence to an existing alignment is partly automated. Although DCSE can be used
      on protein sequence alignments, it is especially targeted at the examination of
      RNA. The secondary structure for every sequence can be incorporated easily in the
      alignment. DCSE also has extensive built-in support for finding and checking
      secondary structure elements. A sophisticated system of markers allows notation
      of special positions in an alignment. This system can be used to store
      information such as the position of hidden breaks, introns and tertiary structure
      interactions.

PMID- 7511480
TI  - [Advances in urologic surgery].

PMID- 7511481
TI  - Forskolin and isoproterenol effect discrete responses on epidermal growth factor
      induced DNA synthesis in aortic smooth muscle cells.
AB  - Defining the mechanisms regulating the proliferation of vascular smooth muscle is
      necessary to better understand the pathogenesis of atherosclerosis and
      hypertension. In the present investigation, we examined the effects of incubation
      with forskolin or isoproterenol on the proliferation of cultured rat aortic
      smooth muscle cells. Forskolin, a direct activator of adenylate cyclase, and
      isoproterenol, a beta-adrenergic agonist, increased intracellular cyclic AMP
      levels in a concentration-dependent manner, subsequent to a 5-min exposure.
      Isobutylmethylxanthine at 100 microM attenuated epidermal growth factor
      stimulated DNA synthesis by 35% without affecting intracellular cyclic AMP
      levels. Forskolin dose-dependently augmented this inhibition. In contrast, a 24-h
      exposure of cells to isoproterenol resulted in a biphasic effect on growth factor
      stimulated thymidine incorporation. Both forskolin and isoproterenol attenuated
      thymidine incorporation to the same degree up to 12 h poststimulation, the onset
      of S phase. By 16 h poststimulation, [3H]thymidine incorporation in smooth muscle
      cells treated with isoproterenol was significantly enhanced by 50%, whereas
      forskolin treatment continued to attenuate DNA synthesis by 40%. Somewhat
      surprisingly, this disparity in effect on DNA synthesis was evident in spite of
      heterologous desensitization to rechallenge by either forskolin or isoproterenol
      subsequent to a 24-h incubation with either drug. These results suggest that the
      isoproterenol enhancement of epidermal growth factor stimulated DNA synthesis in
      rat aortic smooth muscle cells may be cyclic AMP independent.

PMID- 7511482
TI  - Luminal nutrients alter tight-junction permeability in the rat jejunum: an in
      vivo perfusion model.
AB  - The regulation of tight-junction permeability between enterocytes has been
      studied using in vitro perfused loops, Ussing chambers, and cultured cell
      monolayers. In this communication we demonstrate the ability of an in vivo
      perfusion model to monitor tight-junction permeability and respond appropriately
      to physiological luminal stimuli. By using the highly charged anionic
      ferrocyanide molecule, water flux could be accurately assessed in the rat, and
      the luminal clearance of high molecular weight dextrans could be used to probe
      the opening and closing of the paracellular pathway. By utilizing two different
      molecular weight dextrans markers simultaneously, each conjugated with a
      different fluorophore, we were able to calculate luminal clearances of these
      compounds by fluorometric techniques in the presence of luminal nutrients that
      have previously been demonstrated to open intercellular tight junctions. In the
      absence of luminal nutrients or the presence of a non-nutrient sugar such as
      mannitol, clearance of these compounds was negligible. However, with the addition
      of either D-glucose or L-alanine, clearance of both high molecular weight markers
      increased dramatically. Thus, opening of tight junctions between enterocytes
      appears to be a physiological event that occurs in vivo under conditions likely
      to be found in the lumen. Polyethylene glycol 400 (PEG-400) clearance did not
      correlate well with the clearance of either dextran marker, suggesting that this
      probe utilizes a different permeation pathway and may not be appropriate to
      quantify the nutrient-regulatable pathway observed with the former probes.

PMID- 7511484
TI  - Transglycosylation reaction of maltotriose-forming amylase from Streptomyces
      griseus.
AB  - A maltotriose-forming amylase from Streptomyces griseus produced predominantly p
      nitrophenyl alpha-maltotetraoside through a transglycosylation reaction from
      maltotetraose as a donor and p-nitrophenyl alpha-D-glucopyranoside as an acceptor
      in an organic co-solvent. With p-nitrophenyl beta-D-glucopyranoside acceptor, the
      enzyme catalyzed the formation of an alpha-(1-->3)-linked tetrasaccharide (p
      nitrophenyl 3(1)-O-alpha-maltotriosyl-beta-D-glucopyranoside) in a yield of 16%,
      based on the acceptor added with its isomer p-nitrophenyl beta-maltotetraoside.
      This was also the case for the formation of o-chloro-p-nitrophenyl 3(1)-O-alpha
      maltotriosyl-beta-D-glucopyranoside with o-chloro-p-nitrophenyl beta-D
      glucopyranoside acceptor. The results shows that the anomeric configuration of
      the aryl group in the glucosyl acceptors had an effect on the position of
      transglycosylation.

PMID- 7511483
TI  - Pasteurella haemolytica leukotoxin induces histamine release from bovine
      pulmonary mast cells.
AB  - Pasteurella haemolytica A1 leukotoxic culture supernatant was evaluated for its
      ability to induce histamine release from bovine pulmonary mast cells isolated by
      enzymatic dispersion of lung tissue. Histamine was measured by a radioimmunoassay
      technique. Leukotoxic culture supernatant of P. haemolytica significantly
      released histamine in a time and concentration-related manner. This effect was
      lost when culture supernatant was heat-inactivated or preincubated with
      leukotoxin neutralizing rabbit serum. Preincubation of the mast cells with
      propranolol or p-bromophenacyl bromide reduced the histamine-releasing effect of
      leukotoxin, while verapamil enhanced release. Experimental infection of calves
      with P. haemolytica A1 reduced the total histamine content of pulmonary mast
      cells recovered at postmortem. Histamine release induced by P. haemolytica
      leukotoxin is likely an important factor in the pathogenesis of bovine pneumonic
      pasteurellosis.

PMID- 7511485
TI  - [Prevalence of HBV and HCV infections in plasma donors with recently increased
      ALT level].
AB  - HCV and HBV markers in sera were examined in a group of donors (71 cases) who had
      a history of elevated ALT, and were compared with another group of blood donors
      (217 cases) who had no such a history. The results showed that the positive rates
      in both two groups of donors were 14.08% and 6.45% for anti-HCV, 3/8 and 2/13 for
      anti-HCV-IgM in anti-HCV positive cases, 2.82% and 0.46% for HBsAg, 32.39% and
      25.35% for anti-HBs, 45.07% and 33.18% for anti-HBc, respectively (P < 0.05
      0.01). It showed a good correlation between the positive rates of HCV and HBV
      markers and the times of ALT elevation.

PMID- 7511486
TI  - [Investigations on hepatitis C virus infection among heterosexuals with multiple
      partners and patients with sexually transmitted diseases].
AB  - The seroprevalence of antibody against hepatitis C virus (HCV) was assessed by an
      enzyme-linked immunosorbent assay (ELISA) in 110 heterosexually transmitted
      diseases (STDs), 98 heterosexuals with multiple partners, and 107 blood donors.
      The serum samples were also tested for hepatitis B virus surface antigen (HBsAg)
      and antibody against hepatitis B core antigen (anti-HBc). Of the patients with
      STDs 12.7% (13/110) were anti-HCV antibody positive; of heterosexuals with
      multiple sexual partners, 4.1% (4/98) positive; of blood donors, 1.87% (2/107)
      positive. Among the 18 cases of HCV infection, 3 were positive for HBsAg and 10
      were positive for anti-HBc antibody. There was no relationship among HCV
      infection, sex and age in observed objects. From the present data, we can
      conclude that HCV infection should not be ignored in heterosexuals with multiple
      partners and patients with STDs, and the risk factor for HCV infection appeared
      to be associated with a history of STDs and with HBV infection.

PMID- 7511487
TI  - Dextran vs. hydroxyethylstarch in inhibition of postischemic leukocyte adherence
      in striated muscle.
AB  - Microvascular injury associated with ischemia/reperfusion (I/R) is characterized
      by both "no reflow" and "reflow paradox." Prophylactic isovolemic hemodilution
      with dextran 60 to a hematocrit of 30% has been shown to prevent I/R-induced
      capillary no reflow in striated muscle. The objective of the present study was to
      analyze whether hemodilution prior to ischemia has the potential to reduce
      postischemic leukocyte-endothelium interaction, which is known to be one of the
      major components of I/R-induced reflow paradox. Syrian golden hamsters (n = 21)
      were fitted with a dorsal skinfold chamber, which contains striated muscle and
      subcutaneous tissue and allows for repetitive analyses of the microcirculation by
      means of intravital fluorescence microscopy. Four hr of pressure-induced ischemia
      and 30 min of subsequent reperfusion (controls, n = 7) resulted in a significant
      (P < 0.05) increase of microvascular leukocyte accumulation (40,630 +/- 12,731 mm
      3) and adherence to the endothelial lining of postcapillary venules (74.2% +/-
      11.5%) when compared to preischemic baseline (7,502 +/- 1,700 mm-3 and 3.4% +/-
      1.0%, respectively). Recovery was not complete after an observation period of 24
      hr reperfusion [13,735 +/- 2,666 mm-3 (P < 0.05) and 18.5% +/- 6.0% (P < 0.05)].
      Prophylactic isovolemic hemodilution with 6% dextran 60 (Dx60) to a hematocrit of
      30% (Dx60, n = 7) significantly attenuated postischemic leukocyte accumulation
      (23,402 +/- 13,837 mm-3; P < 0.05 vs. controls) and adherence (22.6% +/- 6.4%; P
      < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511488
TI  - Excretion of 3,6-epoxydicarboxylic acids in peroxisomal disorders.
AB  - The urinary excretions of several organic acids were quantitatively studied by
      gas chromatography/mass spectrometry in subjects with disorders of peroxisome
      biogenesis (n = 8) and controls (n = 26). The excretion of 3,6
      epoxtetradecanedioic acid was significantly elevated in all subjects with
      disorders of peroxisome biogenesis (1.8-20.8; controls, not detected-0.5,
      mumol/mmol of creatinine). 3,6-Epoxydodecanedioic acid excretion was usually
      elevated (1.4-19.8; controls, not detected-4.2) and 3,6-epoxyoctanedioic acid
      excretion was not elevated not detected-8.8; controls, 0.6-9.5 mumol/mmol of
      creatinine). It is suggested that measurement of 3,6-epoxydicarboxylic acids may
      be useful for the diagnosis of these disorders.

PMID- 7511489
TI  - The relationship between serum levels of lipoprotein(a) and proteins associated
      with the acute phase response.
AB  - The association of serum lipoprotein(a) (Lp(a)) with inflammation was
      investigated in a primarily rheumatologic study group (n = 570; 202 males and 368
      females) by studying the relationship between serum levels of Lp(a) and a panel
      of acute phase proteins (C-reactive protein (CRP), alpha 1-antitrypsin (AAT),
      alpha 1-acid glycoprotein (AGP), haptoglobin (HPT), complement components 3 and 4
      (C3, C4), prealbumin (PAL), albumin (ALB) and transferrin (TRF)). Lp(a) data were
      adjusted for age and sex, but not clinical condition as no significant
      differences in Lp(a) levels were observed, using analysis of variance, among the
      15 diagnostic categories in the study group. Univariate analyses revealed
      significant positive associations between Lp(a) levels and levels of C4, AGP, C3
      and HPT. Multivariate analysis revealed that C4 and AGP (in descending order of
      significance) were significant independent predictors of Lp(a) concentration,
      together accounting for 2.9% of the variability in Lp(a) concentration in the
      present study group. The data indicate that confounding effects of an acute phase
      response should be considered in epidemiologic studies, if a high prevalence of
      inflammation is suspected.

PMID- 7511490
TI  - Additional tests of interest to the dermatologist.
AB  - The carcinoid syndrome and its clinical manifestations have been discussed. The
      standard laboratory test for making that diagnosis is urinary 5-HIAA levels but
      newer, more sensitive tests may also be available.

PMID- 7511491
TI  - Laboratory tests for ichthyosis.
AB  - To summarize briefly, the suggested laboratory tests to diagnose the ichthyoses
      are listed below. Ichthyosis vulgaris: Skin biopsy if necessary. RXLI: Steroid
      sulfatase activity or levels of cholesterol sulfate. CIE/LI: Usually no
      laboratory test indicated. Epidermolytic hyperkeratosis: Skin biopsy; consider
      keratin gene studies. CHILD syndrome: Usually no laboratory tests needed;
      radiographic studies. Chondrodysplasia punctata: Usually no laboratory studies
      needed; radiographic studies. IBIDS: Hair shaft examination, including
      polarization. KID syndrome: Skin biopsy if necessary. Netherton's syndrome: Hair
      shaft examination. Neutral lipid storage disease: Check blood smear for vacuoles;
      skin biopsy (frozen). Refsum's disease: Plasma phytanic acid levels. Sjogren
      Larsson syndrome: Assay of FAO activity.

PMID- 7511492
TI  - Effect of local inhibition of nitric oxide synthesis on forearm blood flow and
      dorsal hand vein size in patients with alcoholic cirrhosis.
AB  - 1. Nitric oxide (NO) is a potent endogenous vasodilator and plays a role in the
      control of resting vascular tone. Patients with cirrhosis have a hyperdynamic
      circulation with reduced blood pressure and decreased peripheral resistance, and
      it is possible that increased production of NO due to induction of NO synthase
      may be involved in maintaining this vasodilatation. We have examined this
      possibility by studying the effects of local infusions of NG-monomethyl-L
      arginine (an inhibitor of NO synthase) in the forearm arteriolar bed and the
      superficial dorsal hand veins of patients with alcoholic cirrhosis. 2. Drugs were
      either infused locally into the brachial artery and forearm blood flow was
      measured by venous occlusion plethysmography, or into a vein on the back of the
      hand and vein diameter was measured using a linear displacement technique. 3.
      Basal forearm blood flow was increased and vascular resistance was decreased in
      the patients with alcoholic cirrhosis compared with healthy control subjects.
      Noradrenaline and NG-monomethyl-L-arginine caused dose-dependent falls in forearm
      blood flow in both healthy control subjects and patients with cirrhosis. There
      was no significant difference in the responses to either noradrenaline or NG
      monomethyl-L-arginine between the two groups. 4. In the superficial hand veins
      there was no change in vein size in response to NG-monomethyl-L-arginine infused
      alone, and venoconstriction to local infusion of noradrenaline was unaffected by
      co-infusion with NG-monomethyl-L-arginine. 5. Our results confirm that patients
      with alcoholic cirrhosis are vasodilated compared with healthy control
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511493
TI  - Comparative in vitro study of contraceptive agents with anti-HIV activity:
      gramicidin, nonoxynol-9, and gossypol.
AB  - Gramicidin, a polypeptide antibiotic derived from Bacillus brevis, was compared
      in vitro with the established contraceptive virucidal agents nonoxynol-9 and
      gossypol for activity against human immunodeficiency virus (HIV) infection. The
      effective antiviral 10 ng/ml concentration of gramicidin required for complete
      HIV inactivation was a thousand-fold lower than the dose observed for nonoxynol-9
      or gossypol. Gramicidin, routinely used as a contraceptive agent in the former
      Soviet Union, should be considered for in vivo trials as a spermicide with potent
      antiviral activity.

PMID- 7511494
TI  - Comparison of the hemodynamic and oxygen transport responses to modified fluid
      gelatin and hetastarch in critically ill patients: a prospective, randomized
      trial.
AB  - OBJECTIVE: To compare the hemodynamic and oxygen transport responses to a rapid
      (< 10-min) infusion of 500 mL of modified fluid gelatin (group A) or hydroxyethyl
      starch (group B) in patients suffering from acute hypovolemia. DESIGN:
      Prospective, randomized, noncrossover study. SETTING: University hospital,
      general intensive care unit. PATIENTS: Twenty-eight patients with hypovolemia
      mechanically ventilated for concurrent acute respiratory failure. INTERVENTIONS:
      Patients were mechanically ventilated. Pulmonary and femoral artery catheters
      were used for hemodynamic monitoring. MEASUREMENTS AND MAIN RESULTS: Hemodynamic
      and oxygen transport variables were determined at baseline, 15 mins, and 30 mins
      after the infusion of each fluid. In both groups pulmonary artery occlusion
      pressure, stroke volume, and cardiac index significantly increased. In neither
      group did heart rate decrease. Oxygen delivery increased significantly in group A
      patients but not in group B patients. This result was due to greater hemodilution
      in group B patients. CONCLUSIONS: There are no significant differences in the
      hemodynamic responses to hydroxyethyl starch or modified fluid gelatin. The
      hemodynamic and oxygen transport effects of artificial colloid solutions may not
      be entirely predictable and should be monitored in critically ill patients.

PMID- 7511495
TI  - Effect of hydroxyethyl starch on the activity of blood coagulation and
      fibrinolysis in healthy volunteers: comparison with albumin.
AB  - OBJECTIVE: The aim of this study was to investigate whether hydroxyethyl starch
      of medium molecular weight (200 daltons), compared with albumin, has specific
      effects on blood coagulation and fibrinolysis. DESIGN: A prospective, randomized,
      double-blind, crossover trial. SETTING: Laboratory at a university hospital.
      PATIENTS: Ten healthy male volunteers, 23 to 39 yrs old, with no history of
      hypersensitivity, who had normal physical examinations, and were free of a
      bleeding disorder. All patients did not ingest any medications for > or = 2 wks
      before or during the study period. INTERVENTION: Each volunteer received either
      500 mL of hydroxyethyl starch (6% wt/vol, average molecular weight 200
      kilodaltons, molar substitution 0.5 [ratio hydroxyethyl groups/glucose units] in
      0.9% sodium chloride; average molecular weight of 200 kilodaltons) or a control
      of 500 mL of human albumin (5% albumin solution). After a washout period of 4
      wks, subjects crossed over to the alternate treatment. MEASUREMENTS AND MAIN
      RESULTS: Blood samples were taken immediately before infusion and 20, 45, 75,
      105, 165, 285, 405, and 1485 mins after the infusion started. Hematocrit, the
      blood coagulation parameters fibrinogen, activated partial thromboplastin time,
      factor VIII:C, thrombin-antithrombin III complexes, and the fibrinolytic
      parameters fibrin-split product D-Dimer, tissue type plasminogen activator,
      urokinase plasminogen activator, plasminogen activator inhibitor, and plasmin
      antiplasmin complexes were measured. Except for factor VIII:C levels, which were
      significantly lower in the hydroxyethyl starch group, no other significant
      differences in the plasma levels of the parameters mentioned were detected
      between hydroxyethyl starch and albumin infusions. In one volunteer, who had a
      low initial factor VIII:C level of 51%, a decrease to 28% at 165 mins during
      hydroxyethyl starch infusion was found (corresponding albumin value at 165 mins
      was 41%). CONCLUSIONS: a) Medium molecular weight hydroxyethyl starch has a
      specific lowering effect on factor VIII:C concentrations; this phenomenon may be
      hazardous to patients who need full hemostatic competence and who receive medium
      molecular weight hydroxyethyl starch (e.g., as a plasma expander). b) Medium
      molecular weight hydroxyethyl starch does not specifically influence the activity
      of the fibrinolytic system.

PMID- 7511497
TI  - Growth factor gene expression in lung fibroblasts.
AB  - A lung fibroblast cell line was isolated from lung biopsy of a patient with lung
      fibrosis. Gene expression of ten growth factors in the fibroblasts were
      investigated by a reverse transcription-DNA polymerase chain reaction. The
      results indicated that the fibroblasts expressed acidic fibroblast growth factor
      (aFGF) mRNA transcript. Further experiments revealed that recombinant aFGF could
      be internalized by the fibroblasts and stimulated the proliferation of the cells.
      These data suggest that aFGF may activate lung fibroblasts in a way of autocrine
      and, therefore, may be involved in the development of lung fibrosis.

PMID- 7511496
TI  - Increased circulating adhesion molecule concentrations in patients with the
      systemic inflammatory response syndrome: a prospective cohort study.
AB  - OBJECTIVE: To investigate the relationship between the soluble derivatives of
      endothelial adhesion molecules liberated by activated vascular endothelium and
      the development of the systemic inflammatory response syndrome and organ
      dysfunction in septic patients. DESIGN: Prospective cohort study with controls.
      SETTING: University hospital intensive care unit. PATIENTS: Healthy volunteers
      (controls, n = 85), patients with the systemic inflammatory response syndrome (n
      = 21), patients with systemic inflammatory response syndrome and organ
      dysfunction (n = 14), and miscellaneous, severely ill patients (n = 5).
      INTERVENTIONS: Plasma samples were collected from consecutive patients who
      satisfied the criteria for inclusion in the groups listed above. MEASUREMENTS AND
      MAIN RESULTS: The plasma was assayed by enzyme-linked immunosorbent assay (ELISA)
      for each of the three soluble adhesion molecules: sE-selectin, vascular cell
      adhesion molecule-1, and intercellular adhesion molecule-1. There were low basal
      amounts of these adhesion molecules in the healthy volunteers, while plasma
      concentrations of all three adhesion molecules were increased in the sepsis
      groups. The median soluble E-selectin concentration was higher in those patients
      with organ dysfunction compared with the concentrations in patients with
      uncomplicated sepsis (p < .01 at first and p < .001 when comparing peak values
      attained). No patient survived when the amount of soluble E-selectin was > 30
      units/mL. CONCLUSIONS: Concentrations of circulating vascular endothelial
      adhesion molecules, especially soluble E-selectin, are increased in patients with
      systemic inflammatory response syndrome and these concentrations are more
      increased in patients with organ dysfunction. High plasma concentrations of
      soluble E-selectin were closely associated with multiple-organ dysfunction and
      death. Measurement of adhesion molecules, especially soluble E-selectin, might be
      used to advantage in the management of patients with sepsis.

PMID- 7511498
TI  - Positive temporal sharp waves on EEG recordings of healthy neonates: a benign
      pattern of dysmaturity in pre-term infants at post-conceptional term ages.
AB  - One complete sleep cycle was selected in each of ninety-four 3 h EEG recordings
      on 52 healthy neonates from 29 to 43 weeks CA (28 pre-term (PT)/24 full-term
      (FT)); 51 who are neurodevelopmentally normal up to at least 18 months of age.
      Each recording was reviewed to identify positive temporal sharp waves (PTS). This
      wave form was compared to another commonly occurring wave form, temporal theta of
      prematurity (PT theta). 588 PTS and 626 PT theta observations were tabulated in
      terms of frequency, amplitude, morphology, left:right predominance, and sleep
      state at 6 post-conceptional age ranges up to term. Mean PTS for FT, PT and pre
      term at post-conceptional term age (PTT) infants, respectively, were 1.5 +/-
      0.85, 2.8 +/- 2.5, 2.0 +/- 1.6 per sleep cycle. PTS amplitudes (microV) were 59.7
      +/- 23.5, 38.2 +/- 17.8, and 51.8 +/- 29.3. The peak incidence of PTS occurs at
      older post-conceptional ages than PT theta (r = 0.21, P = 0.0001). PTT infants
      had more PTS (chi 2 = 32.5, P = 0.001) than FT infants. Similar numbers and
      descriptions of PT theta were noted between neonatal groups at post-conceptional
      term ages. While pathological PTS waves have been described in FT neonates and
      infants (Chung and Clancy: Electroenceph. clin. Neurophysiol., 1991, 79: 256
      263), benign PTS waves are also present on recordings of healthy pre-term and
      full-term neonates. PTS are electrographically similar to PT theta, but are more
      abundant at older post-conceptional ages in pre-term infants than full-term
      infants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511499
TI  - Physiological significance of sharp wave transients on EEG recordings of healthy
      pre-term and full-term neonates.
AB  - One EEG sleep cycle was selected from each of ninety-four 3 h studies on 52
      healthy neonates from 29 to 43 weeks post-conceptional ages (CA) (28 pre-term
      (PT)/24 full-term infants (FT); 51 are normal up to at least 18 months of age).
      Each record was reviewed to identify sharp wave transients (SWTs). No spike
      discharges were noted. 364 SWTs were tabulated in terms of amplitude, morphology,
      left:right predominance, anatomical site and EEG sleep state. Mean number of SWTs
      per hour for full-term, pre-term, and pre-term at post-conceptional term age
      (PTT) infants were 11.7 (+/- 12), 10.0 (+/- 7), and 13 (+/- 10). Mean amplitudes
      (microV) were 98.8 (+/- 23.2), 84.9 (+/- 38.3), and 99.4 (+/- 28.8) for FT, PT,
      and PTT infants respectively. FP1, FP2, T4 and C3 accounted for 94%, 83% and 84%
      of SWT sites for FT, PT and PTT groups, respectively. Biphasic waves were noted
      more frequently, and triphasic waves almost exclusively in PT infants (chi 2 =
      130.8, P = 0.001). Spearman correlations were significant for amplitude of SWTs
      with CA (and r = 0.45, P = 0.0001). Significant differences (ANOVA) were found,
      for instance, between SWT frequency with the site and sleep state (R2 = 0.63, P =
      0.0001) between SWT amplitude with sleep state and morphology (R2 = 0.59, P =
      0.0001). Brain maturation alters the location and morphology of SWTs in healthy
      neonates. Descriptions of SWTs on EEG recordings of healthy neonates will improve
      the assessment of encephalopathic recordings of infants studied for clinical
      reasons.

PMID- 7511500
TI  - Intraindividual analysis of antiepileptic drug effects on EEG background rhythms.
AB  - Antiepileptic drug (AED) therapy with either phenytoin or carbamazepine has been
      associated with generalized slowing of EEG background rhythms. These effects have
      been seen in groups of patients undergoing AED manipulation, although the
      background slowing has been highly variable from patient to patient. Background
      slowing may represent an objective physiologic measure of drug impact on cerebral
      function and could be useful in monitoring for AED neurotoxicity in individual
      patients. This would require an intraindividual analysis of AED effects on EEG
      background rhythms. The present study was designed to develop a methodology for
      intraindividual analysis of EEG background changes and to apply this methodology
      to patients beginning or ending chronic AED therapy. EEG recordings were obtained
      under controlled conditions in 31 healthy subjects and were repeated after an
      interval of 12-16 weeks. EEG background rhythms from each record were analyzed
      using the fast Fourier transform, and test-retest differences for several
      quantitative measures were calculated from each subject's paired recordings. EEG
      recordings were also obtained in 6 patients beginning or ending chronic AED
      therapy. Test-retest differences for each patient's quantitative EEG measures
      were statistically compared with the distributions of test-retest measures
      obtained from the healthy controls. AED therapy was associated with an increase
      in absolute delta and/or theta power and a slowing of the dominant posterior
      rhythm; however, these EEG background changes varied widely in degree from
      patient to patient. Intraindividual analysis revealed that 5 patients had
      statistically significant slowing relative to the control group on at least 1 of
      the 9 target quantitative EEG measures, as well as a composite measure.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7511501
TI  - Bispectral analysis of the electroencephalogram during induction of anesthesia
      may predict hemodynamic responses to laryngoscopy and intubation.
AB  - The use of electroencephalography as a measure of adequacy of anesthesia has
      achieved limited success. Our purpose was to determine whether the non-linear
      properties of the electroencephalogram (EEG) as defined by the bispectral index
      was a better predictor of autonomic responses to endotracheal intubation during
      opioid-based anesthesia than the linear statistical properties of the EEG
      formulated by power spectral analysis. Thirty-nine adults scheduled for elective
      non-cranial surgery had a continuous EEG recorded during induction of anesthesia
      and endotracheal intubation. Anesthesia consisted of thiopental and nitrous oxide
      in oxygen, followed by 1 of 5 randomized opioid dose regimens. The EEG was
      continuously recorded and blood pressure was measured every minute. All
      electroencephalographic parameters were derived for the 3 min before and after
      intubation and were compared to the blood pressure and heart rate responses.
      Responders were defined by 2 analyses: patients who had a 20% or greater increase
      (1) in blood pressure or (2) in heart rate to laryngoscopy. Responders and non
      responders were compared using Student's unpaired t test, and differences due to
      dose regimens were examined with logistic regression. Based on the criterion for
      blood pressure change, there were 27 responders and 12 non-responders. Heart rate
      changes did not differentiate between the two groups. There was a significant
      difference between response groups as measured by the bispectral index which
      distinguished responders from non-responders independently of the amount of drug
      given. None of the variables of power spectral analysis accurately distinguished
      responder from non-responder.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511502
TI  - Prestimulation-induced modulation of the P300 component of event related
      potentials accompanying startle in children.
AB  - Positive EEG deflections with the latency and scalp distribution of the P300
      accompany startle in response to loud auditory stimuli in a non-task context. The
      purpose of this investigation is to determine if inhibitory and facilitatory
      prestimulation would have effects on the P300 similar to those on the startle
      blink. Prestimulation conditions were chosen to induce startle amplitude
      facilitation (4000 msec sustained tone), startle amplitude inhibition (120 msec
      prestimulation interval), and startle onset latency facilitation (60 msec
      prestimulation interval). Ninety-three boys (including normals and those with
      ADHD and/or enuresis) from a startle modulation study had EEG recordings of
      sufficient quality to provide data for the current study. Repeated measures
      analyses of variance demonstrated startle amplitude and P300 amplitude
      facilitation following the 4000 msec tone, startle amplitude and P300 amplitude
      inhibition following the 120 msec prestimulation interval, and startle onset
      latency and P300 peak latency facilitation (shorter latencies) following the 60
      msec prestimulation interval. Hence, the vertex-recorded P300 elicited by
      startling stimuli was modulated by non-startling prestimulation in a manner that
      paralleled that of modulation of the brain-stem generated startle blink. Startle
      inhibition by prestimulation is mediated by an inhibitory pathway in the
      mesopontine lateral tegmentum. This brain-stem circuitry has a similar effect on
      the P300 even though the latter may be generated in more rostral structures.
      Alternatively, this automatically elicited P300 may represent a limbic or
      cortical reflection of the sensory processing taking place in the brain-stem.
      Either interpretation suggests a "bottom-up" as contrasted with a "top-down" mode
      of sensory processing. This P300 obeys the rules of startle modulation by brain
      stem mechanisms rather than indexing cortical evaluation of stimuli for task
      relevance, stimulus probability, and prior uncertainty.

PMID- 7511503
TI  - The relationship between P300 amplitude and regional gray matter volumes depends
      upon the attentional system engaged.
AB  - Event-related potentials (ERPs) and brain magnetic resonance images (MRIs) were
      acquired from 28 normal men, age 21-60 years. ERPs were recorded during 3
      paradigms designed to elicit automatic or effortful attention, and a combination
      of both. MRI-derived measures of brain gray matter, white matter and cerebral
      spinal fluid (CSF) volumes were computed from frontal, parietal and temporal
      lobes. P300 amplitude correlated significantly with gray matter volumes but not
      with white matter or CSF volumes. Furthermore, the relationships between P300
      amplitude and gray matter volumes reflected functional rather than direct
      topographical relationships: P300 recorded at Pz during automatically elicited
      attention correlated significantly with frontal but not parietal lobe gray matter
      volumes, P300 recorded during effortful attention correlated significantly with
      parietal but not frontal lobe gray matter volumes, and P300 recorded when both
      types of attention were invoked correlated significantly with both frontal and
      parietal gray matter volumes. Startle blinks, also elicited during automatic
      attention-engaging paradigms, were significantly correlated with frontal but not
      parietal lobe gray matter volumes. There was no evidence for a direct spatial
      relationship between P300 amplitude and the gray matter volumes underlying the
      recording electrode.

PMID- 7511504
TI  - A multiple source approach to the correction of eye artifacts.
AB  - Previously published methods correct eye artifacts by subtracting proportions of
      the EOG from EEG electrodes. The implicit assumption made by these methods is
      that the EOG signals are a good measure of eye activity and contain no EEG. In
      this paper a new multiple source eye correction (MSEC) method of eye artifact
      treatment based on multiple source analysis is presented, which incorporates a
      model of brain activity. An accurate, head model-independent estimate of the
      spatial distribution of eye activity can be obtained empirically from calibration
      data containing systematic eye movements and blinks. Using the resulting spatial
      vectors together with the brain model, eye activity in EEG and event-related
      response data can be estimated in the presence of overlapping brain activity and
      corrected. A consequence of the MSEC approach is that data at EOG electrodes can
      be included in analyses of brain activity. In addition, by suitable selection of
      the spatial vectors, the eye activity can be split into signals which identify
      vertical and horizontal movements and eyeblinks. Using auditory ERP data sets
      with and without large eye artifacts, the MSEC method is compared with a
      "traditional" method in which brain activity is not modelled, particularly with
      respect to the spatial distribution of the corrected EEG. Traditional eye
      correction methods are shown to alter the spatial distribution of the EEG,
      resulting, for example, in changes in location and orientation of modelled
      equivalent sources. Such distortion is much reduced in the MSEC method, thus
      enhancing the precision of topographical EEG analyses.

PMID- 7511505
TI  - EEG coherence in Alzheimer disease.
AB  - A novel approach is introduced to examine EEG coherence in different frequency
      bands of 17 locations from the 10-20 system. Fifty patients with clinically
      diagnosed Alzheimer's disease were compared with 42 age-approximated non-demented
      controls. We determined the average coherence between individual electrodes and
      all neighbouring electrodes. Coherence was decreased in the sample of demented
      patients and this effect was most pronounced in the frontal and central
      derivations of the theta, alpha and beta frequency bands. The results can be
      interpreted as the effects of neuronal loss and neocortical disconnection.

PMID- 7511506
TI  - A simultaneous electrocardiogram is important when electroencephalography is used
      in the evaluation of loss of consciousness.
AB  - This study examined the use of electroencephalograms (EEGs) in 2 groups of
      patients with loss of consciousness (LOC), and the importance of a simultaneous
      electrocardiogram (ECG). Each group consisted of 75 patients referred for EEG.
      Group 1 patients (LOC without an established cause) had no clear history of
      convulsive disorder, while group 2 patients (LOC secondary to epilepsy) did. In
      all patients, it was ascertained if any previous cardiac investigations had been
      performed. All patients had an EEG performed with a simultaneous ECG. In addition
      to reporting the EEG, the neurologist reviewed the ECG rhythm and QRS morphology
      from the strip recording in an attempt to use this as a cardiac screening test. A
      cardiologist with the availability of all strip recordings and a subsequent 12
      lead ECG reviewed his findings. The ECG was classified as significantly abnormal
      (potentially capable of causing syncope) in 17% of group 1 patients and 5% of
      group 2. The neurologist, using the simultaneous ECG strip recording only,
      correctly identified 14 of the 17 significantly abnormal ECGs (84%) and 127 of
      the 133 normal cases. In most cases, this was the only ECG evaluation as the EEG
      was performed without any prior cardiac investigation in 53% of group 1 patients
      and 92% of group 2. In conclusion, the EEG was often used as an initial
      investigation in these patients with LOC. A simultaneous ECG strip enabled the
      neurologist to detect most patients with significantly abnormal ECGs or rhythm.
      This will allow appropriate early cardiac review of these patients.

PMID- 7511507
TI  - Differences in the pattern visual evoked potential between pregnant and non
      pregnant women.
AB  - It has been proposed that latencies of some components of the pattern-reversal
      visual evoked potential (PRVEP) are shorter in women than in men because of
      differences in levels of circulating sex steroids. Pregnancy is a time when serum
      levels of oestrogen and progestogen are considerably greater than in the non
      pregnant state. Whole and half field PRVEP latencies and amplitudes have been
      compared in 16 pregnant and 38 healthy non-pregnant women. The mean P100
      latencies for all responses were shorter in the pregnant women, with
      statistically significant differences for the left eye whole field latency (P <
      0.05) and the left eye right and left half field latencies (P < 0.005 and P <
      0.05, respectively) and the right eye right half field latency (P < 0.05). The
      latencies in women in the pregnant group showed a negative correlation with
      gestation, which reached statistical significance for the REWF (r = -0.55, P <
      0.05). These observed differences in PRVEP latencies in pregnant and non-pregnant
      women and the association between latency and gestation are likely to be due to
      differences in circulating sex steroids, and this effect may be the principal
      reason for latency differences between the sexes.

PMID- 7511508
TI  - A comparison of different methods for estimating single-trial P300 latencies.
AB  - Inferences from comparative analyses of reaction time and P300 latency are
      stronger when the various aspects of the distribution across trials are treated
      in the same way for both variables. To this end, a number of studies have
      resorted to estimation of P300 latency at the single-trial level. This report
      presents a comparative evaluation of two common methods for such single-trial
      analysis, i.e., peak-picking and template-matching. Both methods were applied to
      a representative set of real data, comprising different task conditions and two
      age groups. Relevant scoring parameters were varied: low-pass filter settings
      (down to 0.94 Hz) for peak-picking, template duration (250-970 msec) and use of
      covariance vs. correlation for template-matching, and use of a noise-range
      criterion for both methods. It is concluded that peak-picking with a 3.4 Hz
      filter, and template-matching using covariance and template duration between 600
      and 800 msec, are best in terms of sensitivity and reliability, with peak-picking
      surpassing template-matching. Also, the marked increase in the number of rejected
      trials when the noise-range criterion was applied resulted in unwanted modulation
      of behavioral effects of task conditions and age groups.

PMID- 7511509
TI  - Heritable features of the auditory oddball event-related potential: peaks,
      latencies, morphology and topography.
AB  - Baseline auditory ERP data from a larger study of the genetic determinants of the
      response to alcohol were collected from 59 monozygotic (MZ) twin pairs and from
      39 same-sex dizygotic (DZ) twin pairs who drank socially. Three methods for
      measuring genetic influence on the ERPs were applied. First, based on maximum
      likelihood estimates, the heritability of conventional peak amplitude and latency
      of N1 and P3 components was computed for each of 16 lead locations using tests of
      the significance of heritability based on intraclass correlations. P3 amplitude
      provided the strongest results, distributed symmetrically over caudal leads, and
      implied gene dominance as the mode of genetic transmission for the P3 component.
      A substantial genetic influence on N1 latency suggested a mixture of additive and
      dominance effects in the left fronto-temporal regions. N1 amplitude measures
      trended towards significant heritability, but none was observed for P3 latency.
      The second method used the maximum of the cross-correlation function to compare
      wave form shape in a lead-by-lead analysis of data from cotwins. Genetic
      influence was apparent in both target and non-target ERP responses, with a fronto
      central topography of significant results. The third method reduced all spatial
      and temporal ERP differences from a pair of twins to a single scalar number for
      each response. Distributions of this global measure revealed significant genetic
      influence on both non-target and target ERPs. A post hoc analysis of the effect
      of gender on the heritability of N1 or P3 peaks and latencies revealed no
      statistically significant observations in this sample of young adult twins.

PMID- 7511511
TI  - Mismatch negativity to changes in a continuous tone with regularly varying
      frequencies.
AB  - By using the mismatch negativity (MMN) component of the event-related potential,
      it was demonstrated that changes within a repetitively presented tone pattern can
      be automatically (i.e., involuntarily and attention-independently) detected by
      the human brain. Patterns consisting of 5 tones, immediately succeeding one
      another and differing in frequency, were delivered to subjects reading a self
      selected book. There was a frequent, "standard" (P = 0.90) and an infrequent,
      "deviant" (P = 0.10) pattern presented in random order. The deviant pattern
      elicited the MMN even when the auditory stimulation was continuous, that is, no
      empty between-pattern interval indicated the beginning of a tone pattern. It may
      be concluded that the MMN mechanism is not necessarily timed by an "external"
      reference but is able to use "internal" units extracted from the repetitive
      structure inherent in the incessant flow of acoustic signals. The MMN paradigm
      seems to provide a tool to illuminate the organization of acoustic signals into
      auditory units.

PMID- 7511510
TI  - Effects of aging on event-related brain potentials (ERPs) in a visual detection
      task.
AB  - Event-related brain potentials (ERPs) were recorded from 74 subjects (45 men)
      between 18 and 82 years of age in a simple visual detection task. On each trial
      the subject reported the location of a triangular flash of light presented
      briefly 20 degrees laterally to the left or right visual field or to both fields
      simultaneously. ERPs to targets exhibited a similar morphology including P1, N1,
      P2, N2, and P3 components across all age groups. The principal effects of
      advancing age were (1) a marked reduction in amplitude of the posterior P1
      component (75-150 latency) together with an amplitude increase of an anterior
      positivity at the same latency; (2) an increase in amplitude of the P3 component
      that was most prominent over frontal scalp areas; and (3) a linear increase in P3
      peak latency. These results extend the findings of age-related changes in P3 peak
      latency and distribution to a non-oddball task in the visual modality and raise
      the possibility that short-latency ERPs may index changes in visual attention in
      the elderly.

PMID- 7511513
TI  - Equivalent dipole parameter estimation using simulated annealing.
AB  - Equivalent-electrical dipole source modeling of evoked potential signals requires
      complicated non-linear multivariate optimization. Newton and non-linear simplex
      optimization methods often converge to a local minimum, and their results are
      affected by the procedure's starting parameter estimates. This paper describes
      simulated annealing, a more robust and resistant global optimization method. As
      an illustrative example, both the simplex and simulated annealing algorithms were
      used for parameter estimation in modeling wave V of the brain-stem auditory
      evoked potential (BAEP) using a single decaying sinusoid dipole source. Data for
      a single subject from 3000 responses to stimuli on each of 2 days were recorded,
      with modeling performed on 1000 response subaverages. Each estimation problem was
      run with 5 different sets of starting parameters. Simulated annealing always
      converged to the global minimum regardless of the starting parameter estimates
      while simplex often converged to markedly different solutions for different
      starting parameter estimates. No association was apparent between the simplex's
      converging to a local minimum and the closeness of the starting estimates to the
      true parameter values. Implementation of simulated annealing is discussed in
      terms of cooling schedules and other procedure parameters.

PMID- 7511512
TI  - Effects of choice complexity on different subcomponents of the late positive
      complex of the event-related potential.
AB  - The effects of choice complexity on different subcomponents of the late positive
      complex were investigated. In a previous choice reaction study, two subcomponents
      of this complex were identified, called P-SR and P-CR, which seem to be related
      to stimulus evaluation and response selection, respectively. The present study
      attempts to show the dependence of the P-CR (and the independence of the P-SR) on
      response selection by manipulating response selection complexity. This was done
      by having the subjects perform either 2-way or 4-way choice reactions to single
      letter stimuli. To enhance the discriminability of P-SR and P-CR, visual and
      auditory stimuli were used, since the P-SR is modality-dependent. Moreover, the
      stimulus modalities were mixed ("divided attention paradigm"), which was expected
      to lead to a dissociation of P-SR and P-CR, especially after auditory stimuli.
      The choice reaction times were about 100 msec longer for difficult than for easy
      choices. The main ERP result was a 65 msec increase of the P-CR latency for the
      difficult as compared to the easy choice, while the P-SR latency remained
      constant. The P-CR latency difference precisely matched the onset difference of
      the lateralized readiness potential. The P-SR showed a modality-dependent latency
      and topography, while the P-CR did not. The present data confirm the close
      relation of one subcomponent of the late positive complex, the P-CR, to the
      cognitive response-selection process.

PMID- 7511514
TI  - Color VEPs in Parkinson's disease.
AB  - Evoked potential studies have confirmed visual pathway impairment in Parkinson's
      disease. Dopamine is also known to be involved in retinal color vision
      mechanisms. In this study, pattern evoked potentials were recorded in 20
      parkinsonian patients in "on" and "off" conditions to compare the sensitivity of
      black-and-white and color pattern stimuli. Evoked responses to colored patterns
      proved more sensitive to L-DOPA therapy. This finding supports the proposed
      dopamine modulation of the retinal color system and suggests that color pattern
      evoked potential studies might be used in monitoring dopamine therapy in
      parkinsonian patients.

PMID- 7511515
TI  - Pattern reversal evoked potentials: gender differences and age-related changes in
      amplitude and latency.
AB  - This report is intended to complement the current body of literature by
      describing pattern reversal evoked potential (PREP) component amplitudes and
      latencies in a larger sample than has been previously studied and providing
      comparisons of males and females across the lifespan. Binocular PREPs were
      measured from 406 normal subjects, 6-80 years of age. In general, latencies were
      found to decrease during maturation, stabilize across early adulthood, then begin
      to increase sometime after the late 20s. There were minimal gender differences in
      latencies during development but males tended to have longer latencies than
      females during adulthood. Across the lifespan, amplitudes were larger for
      females. Results of regression analyses using the entire data set were compared
      to results of separate regression analyses for developmental years (6-20) and
      adulthood (21-80). Separate analyses appear to provide more useful descriptions
      of PREP latency and amplitude changes across the lifespan. It is clear that
      predicted normal values can vary depending on age range and relative proportion
      of males and females comprising a reference sample. Appropriate clinical values
      should be based on age- and sex-matched normal subjects and should be specific
      with regard to technical and methodological variables.

PMID- 7511517
TI  - Repetitive magnetic nerve stimulation: technical considerations and clinical use
      in the assessment of neuromuscular transmission.
AB  - We assessed to what extent repetitive magnetic stimulation can replace the
      electrical method. Fifteen healthy subjects and 3 patients with myasthenia gravis
      were investigated using stimulation of the median, ulnar, axillary and accessory
      nerves. Single, as well as 3/sec repetitive magnetic and electrical stimuli were
      applied. When comparing the results of magnetic vs. electrical stimulation,
      amplitudes, areas and shapes of compound muscle action potentials were not
      significantly different. Although single magnetic stimuli were much less
      uncomfortable than the electrical stimuli, differences in comfort were much
      smaller in the repetitive protocol, because muscular contractions under the
      magnetic stimulation coil caused unpleasant movements of, for example, the neck.
      Additional problems arose from technical limitations of the prototype magnetic
      stimulator used: stimulation intensity was significantly limited, resulting in an
      inability to elicit supramaximal responses in 11 of the 154 investigations.
      Overheating of the stimulator coil forced us to give the coil extra time to cool
      down. These problems might be solved in the future by more focused stimulus
      geometry and introduction of cooling devices. It is concluded that magnetic
      stimulation can elicit responses which are equivalent to the electrical method in
      repetitive nerve stimulation. At present due to some shortcomings it cannot
      replace electrical stimulation in routine repetitive nerve stimulation.

PMID- 7511516
TI  - Repetitive discharge due to self-ephaptic excitation of a motor unit.
AB  - Repetitive discharges (RDs) of a motor unit action potential were evoked by nerve
      stimulation in chronically denervated muscles of 3 patients. One RD also occurred
      at rest and during voluntary contraction. The 3 RDs had a regular firing
      frequency of respectively 16, 27 and 28.5 c/sec. Double stimulation evoked an RD
      consisting of doublets. An ectopic discharge arising during the RD had the same
      effect. These observations make likely that such RDs result from a 1-way ephaptic
      reverberating excitation occurring within a single MU. The synchronized potential
      of muscle fibres grouped by reinnervation may re-excite an axonal branch of the
      same MU, thus initiating a reverberating loop.

PMID- 7511518
TI  - The polarity of the induced electric field influences magnetic coil inhibition of
      human visual cortex: implications for the site of excitation.
AB  - Human perception of 3 briefly flashed letters in a horizontal array that subtends
      a visual angle of 3 degrees or less is reduced by a magnetic coil (MC) pulse
      given, e.g., 90 msec later. Either a round or a double square MC is effective
      when the lower windings or central junction region, respectively, are tangential
      to the skull overlying calcarine cortex and symmetrical across the midline. The
      modeled, induced electric field has peak amplitude at the midline, but the peak
      spatial derivatives lie many centimeters laterally. Thus, the foveal
      representation near the midline is closer to the peak electric field than to its
      peak spatial derivatives, i.e., excitation of calcarine cortex differs from
      excitation of a straight nerve. With an MC pulse that induces an electric field
      which is substantially monophasic in amplitude, the lateral-most letter (usually
      the right-hand letter) in the trigram is preferentially suppressed when the
      electric field in the contralateral occipital lobe is directed towards the
      midline. Inferences from using peripheral nerve models imply that medially
      located bends in geniculo-calcarine or corticofugal fibers are the relevant sites
      of excitation in visual suppression; end excitation of fiber arborizations or
      apical dendrites is considered less likely. This conclusion is supported by the
      fact that the induced electric field polarity in paracentral lobule for optimally
      eliciting foot movements is opposite to that for visual suppression, the major
      bends occurring at different portions of the fiber trajectories in the two
      systems.

PMID- 7511519
TI  - Cerebro-cerebellar interactions in man: neurophysiological studies in patients
      with focal cerebellar lesions.
AB  - Recently Ugawa and co-workers reported that motor cortex excitability after
      magnetic stimulation in man can be reduced by coupling an electrical transcranial
      stimulus over the base of the skull. They hypothesised that the motor cortex
      inhibition observed was determined by activation of cerebellar structures.
      Nevertheless, the paradigm employed did not allow to exclude interference from
      extracerebellar structures due to spread of the electrical stimulus. In order to
      ascertain the role of the cerebellum in determining the modulation of the motor
      cortex excitability we examined, in 10 normal subjects and in 2 patients with
      unilateral cerebellar lesions, the effects of electrical stimuli over the base of
      the skull on the motor responses evoked by cortical magnetic stimulation. In both
      patients no inhibition of motor responses was present in the muscles ipsilateral
      to the lesion, whereas an inhibition, similar to that observed in controls, was
      evident on the opposite side. The present findings suggest the cerebellar origin
      of the motor effects seen after electrical stimulation of the base of the skull
      and further clarify the physiological cerebro-cerebellar interactions in man.

PMID- 7511521
TI  - Non-invasive differentiation of motor cortical representation of hand muscles by
      mapping of optimal current directions.
AB  - Non-invasive mapping of human motor cortex by stimulating different scalp
      positions with a magnetic coil held at a constant orientation allows
      differentiation of proximal and distal arm muscles. This study describes a
      technique for more precise mapping of closely represented muscles using different
      orientations of a coil that delivers nearly monopolar current pulses. EMG was
      recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI),
      abductor digiti minimi (ADM), and flexor carpi radialis (FCR) of 9 normal
      volunteers. Stimuli were delivered from a Dantec stimulator through an 8-shaped
      coil. The center of the coil was kept flat on the scalp on a given position, and
      the coil rotated at different angles. The amplitudes of the motor evoked
      potentials were used for calculation of optimal current directions in the brain
      for activation of each muscle in each position. The optimal current direction for
      FCR activation pointed antero-medially. ADM, FDI and APB mapped progressively
      more antero-laterally. The relationship between current directions was constant
      across subjects and did not change in different scalp positions. This technique
      improves the spatial resolution of non-invasive cortical mapping and may express
      the differences in orientations of interneuronal nets in the precentral gyrus.

PMID- 7511520
TI  - Evaluation of the motor and sensory components of the pudendal nerve.
AB  - Extensive neurophysiological investigations consisting of different techniques to
      evaluate the efferents and afferents of the pudendal nerve were carried out in 27
      healthy subjects. These investigations included motor evoked potential recordings
      from the external anal sphincter in response to magnetic stimulation of the
      cortex and lumbosacral roots, measurement of sacral reflex latency to magnetic
      and electrical stimulation, and cortical sensory evoked potential recording after
      stimulation of the dorso-genital nerve and anal canal. Motor latencies after
      transcranial magnetic stimulation to the anal sphincter were 25.1 +/- 2.9 msec at
      rest and 20.9 +/- 2.0 msec with voluntary sphincter contraction (facilitation).
      Motor latency after lumbosacral root stimulation was 3.7 +/- 1.0 msec. Mean
      sacral reflex latency after magnetic stimulation was 43.8 +/- 11.2 msec and was
      significantly longer than after electrical stimulation (37.0 +/- 7.2 msec; P <
      0.05). P1 latency of the sensory evoked potentials after dorso-genital nerve
      stimulation was 40 +/- 3 msec and was significantly shorter than after anal
      stimulation 46 +/- 3 msec (P < 0.01). Evoked potential recording allows us to
      study both upper and lower motor neuron components to the anal sphincter. The
      present study paves the way for the combined application of these tests in the
      evaluation of disorders of the pelvic floor.

PMID- 7511522
TI  - Task-dependent modulation of short- and long-latency electromyographic responses
      in upper limb muscles.
AB  - Records were made of electromyographic (EMG) responses of both upper limb muscles
      and the corresponding elbow joint movements following sinusoidal (0.3 Hz)
      isometric displacement of the elbow joint itself. Two motor conditions were
      tested. Firstly, the subjects had to control elbow position and secondly control
      joint torque. Randomly timed, flexing or extending ramp impulses were induced at
      different displacement velocities and amplitudes. Following long duration
      displacements (> 100 msec) the recorded EMG responses could clearly be separated
      into 3 different components (M1-M3). The M1 component was of constant duration
      but M3 corresponded to the duration of the ramp displacement. It is proposed that
      the M1 component is "coded" by the acceleration signal and the M3 component by
      the velocity signal. Only the shape of the M2 component was dependent upon the
      actual motor condition. With the subjects controlling the elbow joint angle the
      M2 components in the arm flexor and extensor EMG responses exhibited a peak whose
      rate of rise was dependent on displacement velocity. However, when elbow torque
      was controlled by the subjects the M2 component exhibited a plateau whose
      amplitude was dependent on displacement velocity. The amplitude of the M2
      component was significantly larger during position-control than during torque
      control. We propose that the difference in the behaviour of the EMG responses may
      be achieved by the appropriate central regulation of gamma-motoneurone activity
      or, alternatively, by selective modulation of different receptor inputs between
      the two tasks.

PMID- 7511523
TI  - Conduction pathways and generators of magnetic evoked spinal cord potentials: a
      study in monkeys.
AB  - Evoked spinal cord potentials (ESCPs) following transcranial magnetic stimulation
      were recorded from the spinal cord in monkeys anesthetized with ketamine.
      Isopotential maps of the earlier negative deflection of the magnetic ESCP (N1
      wave) revealed a distribution of negative field potentials, the maximum of which
      were located within the medial dorsolateral funiculus, which corresponds to the
      dorsolateral corticospinal tracts. The N1 wave of the magnetic ESCP had the same
      latency as the D-wave of the electrical ESCP elicited by either direct cortical
      or transcranial electrical stimulation. We assumed that the N1 wave was generated
      by direct excitation of pyramidal axons. Isopotential maps of the waves that
      followed the N1 peak (waves N2, N3, N4, and N5) of the magnetic ESCP showed a
      negative field potential distribution, the maximum of which was at the
      ventromedial funiculus as well as within the medial dorsolateral funiculus. Later
      waves of magnetic ESCP were suggested to reflect not only the dorsal
      corticospinal tracts but also the ventromedial spinal cord function.

PMID- 7511525
TI  - Influence of visual and somatosensory input on leg EMG responses in dynamic
      posturography in normals.
AB  - The contribution of visual and somatosensory input to stabilization after sudden
      postural disturbances was investigated. Fast transient platform movements (50
      degrees/sec, 4 degrees), rotating toe-up around the ankle-joint, evoke EMG
      responses in the triceps surae (TS) and anterior tibial (TA) muscles. The short
      and medium latency responses (SL, ML) in the TS destabilize, the long latency
      responses (LL) in the TA stabilize the upright posture. The influence of vision
      was tested in normals comparing the conditions eyes open with eyes closed. The
      influence of additional somatosensory input was tested with the operator's index
      finger touching the back of the subject with eyes closed. Absent visual input
      (eyes closed) resulted in a decrease in latency of the stabilizing LL response
      and an increase in the integrated EMG (iEMG). With eyes closed the latency of the
      LL response decreased by 4 msec on average (mean eyes open: 111.6 msec (S.D. =
      17.3), eyes closed: 107.6 msec (S.D. = 17.5); P < 0.001 (Wilcoxon test)), the
      iEMG increased by 10% (mean eyes open: 13.9 microV.sec (S.D. = 7.6), eyes closed:
      15.5 microV.sec (S.D. = 8.6); P < 0.001). Additional somatosensory input as an
      external reference for body orientation in space resulted in an increase in
      latency and decrease in iEMG: the latency increased by 7 msec on average (mean
      eyes closed: 107.6 msec (S.D. = 17.5), index finger and eyes closed: 114.7 msec
      (S.D. = 19.9); P < 0.001), the iEMG decreased by 20% (mean eyes closed 15.5
      microV.sec (S.D. = 8.6), index finger and eyes closed: 12.3 microV.sec (S.D. =
      7.5); P < 0.001). There was no significant change in latency of SL and ML. We
      conclude that postural EMG responses in leg muscles after fast transient platform
      movements change according to different functional demands, modulated via visual
      and somatosensory input.

PMID- 7511524
TI  - In vitro evaluation of a 4-leaf coil design for magnetic stimulation of
      peripheral nerve.
AB  - The performance of a 4-leaf magnetic coil was evaluated during magnetic
      stimulation of a peripheral nerve in vitro. The site of stimulation was below the
      coil center, and a 90 degrees rotation of the coil was equivalent to a change in
      current polarity. A hyperpolarizing magnetic stimulus failed to slow or block a
      propagating action potential.

PMID- 7511526
TI  - Standardization of facilitation of compound muscle action potentials using a
      modified myometer during magnetic stimulation in healthy volunteers.
AB  - In 20 normal subjects motor evoked potentials (MEPs) from first dorsal
      interosseous (FDI) were obtained following transcranial magnetic stimulation
      during relaxation and voluntary contraction of 2-20% of maximum. A new method to
      standardize facilitation of MEP using surface EMG and a modified myometer was
      used. The MEP amplitudes increased significantly at contraction levels of 2%, 10%
      and 15% of maximum. The latencies decreased significantly at contraction levels
      of 2%, 5% and 15%. Coefficients of variation of the amplitude decreased from 6.4%
      during relaxation to approximately 2% during facilitation. In contrast,
      coefficients of variation of take-off latencies (T-lat) increased significantly
      from 1.7% during relaxation to approximately 3% during facilitation. The
      variability of amplitudes and latencies was mainly due to inter-individual
      variation. The observations in the present study indicate that the actual
      contraction level should be precisely defined during transcranial magnetic
      stimulation.

PMID- 7511528
TI  - Application of dynamic capillary isoelectric focusing to the analysis of human
      hemoglobin variants.
AB  - Capillary isoelectric focusing (CIEF) with electro-osmotic zone displacement of
      normal and pathological hemoglobins (Hb) is reported. CIEF is performed in
      untreated, open-tubular, fused-silica capillaries of 75 microns internal diameter
      using methylcellulose for dynamic column conditioning. After direct injection of
      hemolysates mixed with carrier ampholytes, high resolution separation of Hb
      variants, including Hb A1c, A, F, D, S, E and A2, is obtained, this permitting
      unambiguous characterization of Hb patterns of normal adults, newborns, patients
      with diabetes, different hemoglobinopathies and thalassemia syndromes.
      Qualitatively, the CIEF data compare well with those obtained by gel isoelectric
      focusing and high-performance liquid chromatography. CIEF is demonstrated to be a
      simple, rapid and fully instrumental approach to Hb analysis. Run times of less
      than 20 min make CIEF an attractive method for routine Hb investigations and
      screening programs.

PMID- 7511527
TI  - Cytogenetic studies in lymphocytes of patients with rectal cancer.
AB  - Spontaneous and clastogen-induced chromosomal instability in a high-risk group
      (i.e, 33 patients with rectal carcinomas) was investigated using peripheral blood
      lymphocytes as target cells. In addition to the analysis of spontaneous and
      clastogen-induced chromosome aberrations, this study also included classical
      karyotype analysis and scoring of sister chromatid exchanges (SCE) in some of the
      patients. Diepoxybutane (DEB), 4-nitroquinoline-1-oxide (NQO), and bleomycin were
      used as standard clastogens. Lymphocytes of healthy control individuals were
      studied in parallel with each cancer patient. While only slight but significant
      differences could be detected of the average spontaneous, DEB- and bleomycin (G2)
      induced chromosome breakage between patient and control lymphocytes, individual
      patients and two of the control individuals showed a more distinct increase in
      the frequency of the studied end points. These increases were documented by a
      variegated mosaicism of karyotypic changes and by an increased breakage rate
      induced by the clastogens. Neither the bleomycin-exposure in the G1 phase nor SCE
      was capable of detecting differences between the patients and controls. Of
      particular interest in the sense of high-risk individuals were seven patients and
      two control persons whose lymphocytes exhibited increased chromosomal sensitivity
      under more than one of the studied experimental conditions.

PMID- 7511529
TI  - Polymerase chain reaction-directed DNA sequencing of bleomycin-induced
      "nondeletion"-type, 6-thioguanine-resistant mutants in Chinese hamster ovary cell
      derivative AS52: effects of an inhibitor and a mimic of superoxide dismutase.
AB  - Bleomycin-induced, 6-thioguanine-resistant, "non deletion" mutants pretreated
      with or without either TRIEN (triethylenetetramine), a superoxide dismutase (SOD)
      inhibitor, or TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a SOD
      mimic, were analyzed by polymerase chain reaction (PCR)-directed DNA sequencing
      in a Chinese hamster ovary (CHO) cell derivative, AS52. Among the 23 bleomycin
      induced mutants, six have 3-bp 5'-TGA-3' deletions in the region of 366-371, five
      have single-base deletions, seven have base substitutions, three have insertions,
      and two have possible translocations. Among the 16 bleomycin-induced mutants
      pretreated with TRIEN, six have the 5'-TGA-3' deletion (366-371), two have single
      base deletions, one has a 13-bp deletion, four have single-base substitutions,
      one has a double-base substitution, and two have insertions. Among the 17
      bleomycin-induced mutants pretreated with TEMPOL, six have the same TGA
      deletions, two have single-base deletions, two have single-base insertions, four
      have single-base substitutions, one mutant has a 12-bp deletion, one has a 13-bp
      deletion, and one mutant shows no detectable change in its coding region in the
      DNA sequence. A possible shift from a ROS-mediated mutational spectrum to a
      spontaneous mutational spectrum by TRIEN further indicates that reactive oxygen
      species play an important role in bleomycin mutagenesis in mammalian cells.

PMID- 7511531
TI  - Control of cellular iron homeostasis by iron-responsive elements in vivo.
AB  - It has recently been proposed that cellular iron homeostasis in mammalian cells
      is regulated at the post-transcriptional level by the reciprocal control of
      transferrin receptor and ferritin mRNA expression via an iron-regulatory factor.
      This iron-regulatory factor has been shown to be a cytoplasmic aconitase which
      can bind to iron-responsive elements in the corresponding mRNAs with greater or
      lesser affinity as a function of the iron status of the cell. In the present
      study, we show that in vivo the affinity of iron-regulatory factor for iron
      responsive elements in liver reflects the long-term iron status of the tissue in
      animal models for iron overloading and iron deficiency, when combined with
      altered transferrin saturation and serum iron levels. In contrast hepatic iron
      overload achieved without altering such haematopoeitic indices, had a less
      pronounced effect. In both spleen and heart, the affinities of iron-regulatory
      factor changed in parallel with both altered iron status and haematological
      markers. In brain and duodenum, there were no consistent changes in iron
      regulatory-factor activity with iron loading or depletion. Iron-regulatory-factor
      activity in kidney responded in an as yet unexplained manner.

PMID- 7511532
TI  - Cross-reactivity between the mannan of Candida species, Klebsiella K24
      polysaccharide and Salmonella C1 and E O-antigens is mediated by a terminal non
      reducing beta-mannosyl residue.
AB  - Rat monoclonal antibody MASC1-MR9 (MR9) binds to a mannan of Candida species and
      the O-antigenic polysaccharides of Salmonella bacteria of serogroups C1 (CO) and
      E (EO). Mannan and glycoconjugates comprising BSA and O-antigen polysaccharides,
      decasaccharide-BSA (CO-BSA) or trisaccharide-BSA (EO-BSA), inhibited each other's
      reactivity with MR9. The saccharides beta-D-Manp-(1-->6)-alpha-D-Manp-1-OMe, beta
      D-Manp(1-->3)-alpha-D-Manp-1-OMe, beta-D-Manp(1-->2)-alpha-D-Manp-1-OMe
      (corresponds to the terminal non-reducing end of Salmonella serogroup C1 O
      antigen) and beta-D-Manp(1-->4)-alpha-L-Rhap(1-->3)-alpha-D-Galp-1-O-p-++
      +trifluoroacetamido aniline (corresponds to the backbone of Salmonella serogroup
      E O-antigen) inhibited the binding of MR9 to these antigens whereas alpha-D
      Manp(1-->3)-alpha-D-Manp-1-OMe and alpha-D-Manp(1-->4)-alpha-L- Rhap-1-O-p
      nitrophenyl did not. Saccharides (3-10 residues) of mammalian origin with
      terminal and internal Manp alpha-1-->2, Manp alpha-1-->3 and Manp alpha-1-->6
      residues also failed to inhibit at any concentration. None of the saccharides
      with internal beta-mannosyl residue was able to inhibit the MR9 antibody.
      Monosaccharides D-mannose, beta-D-Manp-1-OMe and 1,5 anhydro-D-mannitol inhibited
      the MR9 monoclonal antibody whereas alpha-D-Manp-1-OMe, beta-D-Glcp-1-OMe, and
      beta-D-Galp-1-OMe did not. In addition a Klebsiella K24 capsular polysaccharide
      containing a beta-D-Manp(1-->4)-alpha-D- GlcA (GlcA, glucuronic acid) as a
      structural element possessed an inhibitory activity. MR9 therefore recognizes an
      epitope within beta-mannose monosaccharide residues at the terminal non-reducing
      ends of carbohydrate chains in mannan, and polysaccharides in Salmonella
      serogroups CO and EO and Klebsiella K24.

PMID- 7511530
TI  - Characterization of a 100-kDa heat-stable microtubule-associated protein from
      higher plants.
AB  - In higher-plant cells, the different cell-cycle-dependent microtubule arrays are
      involved in a wide range of activities including chromosome segregation, cell
      plate formation and cellulose microfibril distribution and orientation. A wealth
      of data, obtained using animal cells, has indicated that the differential
      stability and function of microtubules during cell-cycle and/or differentiation
      could be primarily regulated by selective microtubule-associated proteins (MAP).
      Compared to animal MAP, our knowledge of plant MAP is so far very limited. In
      this study, we have identified a maize heat-stable protein with apparent
      molecular mass 100 kDa (P-100) which binds to taxol-stabilized neurotubules and
      copolymerizes in vitro with purified neural tubulin. Moreover, P-100 cross-reacts
      with affinity-purified tau antibodies like a maize 83-kDa putative MAP described
      previously [Vantard, M., Schellenbaum, P., Fellous, A. & Lambert, A. M. (1991)
      Biochemistry 30, 9334-9340]. Polyclonal antibodies directed against P-100 were
      obtained and indicated that this protein is found in diverse higher-plant
      cultured cells suggesting the ubiquitous nature of this protein. P-100 can be
      phosphorylated in vitro by protein kinases present in a maize cytosol extract.
      Together, our data suggest that P-100 could be a higher plant MAP.

PMID- 7511533
TI  - House dust mite allergy: from T-cell epitopes to immunotherapy.
AB  - CD4+ T-lymphocytes induce and regulate allergic inflammatory responses to common
      environmental aeroallergens derived from Dermatophagoides spp. (house dust mite,
      HDM), which cause clinical symptoms in approximately 10% of the population.
      Definition of the molecular structure of HDM proteins combined with the ability
      to isolate monoclonal populations of human CD4+ T-cells representative of the
      'interleukin-4 (IL-4) dominant' functional phenotype, which support
      immunoglobulin E (IgE) synthesis, has allowed T-cell recognition of HDM to be
      examined in detail. The results of these investigations demonstrated extensive
      heterogeneity in both the antigen and HLA class II restriction specificity of the
      HDM reactive T-cell repertoire. Furthermore, long-lived clones of T-cells with
      oligoclonality in T-cell antigen receptor (TcR) usage, driven by chronic
      stimulation with HDM, have been identified in human peripheral blood. The
      presentation of specific peptides and superantigens under conditions that induce
      T-cell non-responsiveness has provided an in vitro model for analysing the
      mechanisms of CD4+ T-cell targeted immunotherapy. It appears that the mechanisms
      underlying T-cell anergy are accompanied by a transient downregulation of TcR and
      CD28 and mediated by a shift in the cytokine profile from that of the 'IL-4
      dominant' to the 'interferon-gamma (IFN-gamma) dominant' functional phenotype of
      CD4+ T-cells. In parallel, using a murine model, it has been demonstrated that
      administration of an immunodominant peptide via the mucosal surfaces of the
      respiratory and alimentary tracts may tolerize an established response to intact
      HDM proteins. The potential application of these models in the development of
      novel approaches to immunotherapy is discussed.

PMID- 7511534
TI  - Reversible translocation of glycoprotein Ib in plasmin-treated platelets:
      consequences for platelet function.
AB  - Understanding the effect of fibrinolysis on platelet function is of clinical
      importance. Plasmin is recognized to affect platelet adhesive function by
      reducing the interaction of platelet glycoprotein (GP) Ib with von Willebrand
      factor (vWF) bound to the subendothelium. This platelet function is commonly
      explored in vitro by the ristocetin-induced agglutination test. Our previous
      study demonstrated a plasmin-induced redistribution of GP Ib molecules from the
      platelet surface to the linings of the surface-connected canalicular system
      (SCCS), a critical mechanism for understanding plasmin-induced GP Ib dysfunction.
      Here, we demonstrate that neutralization of plasmin by its inhibitors, aprotinin
      or tripeptide Val-Phe-Lys-CH2Cl, permits a time dependent recovery (within 30
      min) of ristocetin-induced agglutination in the platelets which were stimulated
      by plasmin at < 1 CU ml-1. This functional recovery was accompanied with a
      restoration of a normal amount of GP Ib on the platelet surface, as measured by
      the binding of both monoclonal anti-GP Ib antibody SZ 2 and 125I-labelled vWF to
      the platelets. Cytochalasin D did not inhibit this recovery, suggesting that this
      process may be due to passive actin depolymerization. These findings were further
      confirmed by immunoelectron microscopic study. Utilizing the platelets pre
      labelled with anti-GP Ib antibody prior to plasmin stimulation, it was
      demonstrated that the observed recovery is due to a reverse translocation from
      the SCCS to the plasma membrane of the same GP Ib molecules which were present
      initially at the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511535
TI  - Effects of recombinant tumour necrosis factor (rTNF-alpha) in cancer.
      Observations on the acute phase protein reaction and immunoglobulin synthesis
      after high dose recombinant TNF-alpha administration in isolated limb perfusions
      in cancer patients.
AB  - To obtain insight in the effect of TNF on the synthesis of acute phase proteins
      like CRP, alpha 1-antitrypsine, alpha 1-acidglycoprotein, C3 and C4 and the
      immunoglobulins (IgG-M-A), nine cancer patients who were treated with an isolated
      limb perfusion (ILP) with high dose recombinant TNF-alpha (rTNF-alpha) were
      investigated during a 7-day period after the end of the perfusion. Resorption of
      rTNF-alpha from out of these limbs into the circulation after the ILP induced
      within 30 min to 6 h in all patients elevated serum levels of IL-6. At the same
      time C-reactive protein became detectable in serum. The highest serum levels were
      obtained at 48 h after ILP. The serum levels of the other acute phase proteins
      (alpha 1-acidglycoprotein, alpha 1-antirypsine, C3, C4), rose more slowly and the
      highest serum levels were found at the third day. All investigated proteins
      declined after they had reached their peak levels. Levels of alpha 1
      acidglycoprotein and alpha 1-anti-trypsin alpha 1-acid declined slower than both
      complement component. In regard to the immunoglobulin levels a nearly continuous
      increase in the serum level of specifically IgM was observed. This study clearly
      shows the interrelationship between TNF-alpha and IL-6 in regard to the synthesis
      of the different acute phase proteins; and moreover also a striking effect on IgM
      synthesis.

PMID- 7511536
TI  - Spontaneous bacterial peritonitis is associated with high levels of interleukin-6
      and its secondary mediators in ascitic fluid.
AB  - We investigated 37 patients with ascites and liver cirrhosis in order to examine
      whether on the basis of correlation of cytokines and acute phase proteins of the
      ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made.
      Significantly enhanced levels of interleukin-6, as well as acute phase reactants
      alpha-1-antitrypsin and C-reactive protein were found in the ascitic fluid of
      patients with spontaneous bacterial peritonitis. The levels of tumour necrosis
      factor alpha (TNF-alpha), neopterin, interleukin 2-receptor and granulocyte
      macrophage colony stimulating factor were higher in patients with spontaneous
      bacterial peritonitis, but without statistical significance, whereas no
      differences were found between the interferon gamma, interleukin-2 and
      interleukin-1 levels. In addition, interleukin-6, TNF-alpha and neopterin levels
      were found to correlate significantly with the outcome of the disease. These
      findings show that acute phase reaction occurs in the ascitic compartment in
      correlation with the development of spontaneous bacterial peritonitis.

PMID- 7511537
TI  - Hepatitis C virus-related autoimmunity in patients with porphyria cutanea tarda.
AB  - Hepatitis C virus (HCV) infection is frequently found in autoimmune hepatitis and
      mixed cryoglobulinaemia. In these conditions HCV could be responsible for immuno
      mediated organ alterations. The aim of this study was to evaluate the presence of
      immunological alterations in PCT patients, in which HCV infection has been
      frequently found. Twenty-three PCT patients were evaluated for clinical and
      serological alterations, including: chronic hepatitis, other systemic symptoms,
      serum cryoglobulins and rheumatoid factor (RF), haemolytic complement, serum
      immunoglobulins, anti-nuclear (ANA), anti-smooth muscle (ASMA), anti-liver-kidney
      microsomal (anti-LKM1), anti-soluble-liver-antigen (SLA), anti-mitochondrial
      (AMA), anti-GOR antibodies, anti-HCV and HCV RNA. Abnormal serum ALT were present
      in the majority of cases (20/23, 87%), while liver biopsy revealed a chronic
      persistent hepatitis or chronic active hepatitis in 15/20 (75%) PCT patients. In
      a high percentage of subjects (91%) the presence of anti-HCV was detected by
      ELISA and RIBA II (Chiron, Emeryville CA, USA). In 17/22 (77%) cases the ongoing
      HCV replication in the serum was demonstrated by the detection of HCV genomes
      (polymerase chain reaction). The prevalence of both anti-HCV and HCV RNA in PCT
      was significantly higher if compared to 22 systemic immunological diseases (P <
      0.001) and 47 healthy subjects (P < 0.001). A possible HCV-induced autoimmunity
      in PCT was suggested by the presence of the following immunological parameter
      alterations: anti-GOR in 13/23 (57%), ANA in 4/23 (17%), ASMA in 18/23 (78%),
      anti-LKM1 in 1/23 (4%), RF in 23/23 (100%), mixed cryoglobulins in 4/23 (17%),
      complement consumption in 10/23 (43%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511538
TI  - Nitric oxide synthase localization in cultured cerebrovascular endothelium during
      mitosis.
AB  - Nitric oxide synthase (NOS) is present in cultured endothelial cells of
      cerebrovascular origin in a unique membrane-bound subcellular distribution. The
      enzyme can be detected by its ability to reduce nitro blue tetrazolium to an
      insoluble dense blue formazan precipitate. In resting cells, enzyme is located
      adjacent to the nuclear membrane in a single focus with very faint staining in
      the cytoplasm. During the various stages of cell division, however, NOS becomes
      redistributed in a pattern which appears similar to that of the Golgi complex.
      Enzyme is found concentrated near the spindle during early prophase and
      metaphase. During anaphase and telophase, NOS appears to also spread into the
      cytoplasm for redistribution into the daughter cells.

PMID- 7511539
TI  - Comparison of cellular and nuclear flow cytometric techniques for discriminating
      apoptotic subpopulations.
AB  - We compared cellular flow cytometric methods employing carboxyfluorescein (CF),
      Hoechst 33342, and Hoechst 33258 with a nuclear method in their ability to
      discriminate apoptotic subpopulations in rat thymocyte cultures exposed to
      dexamethasone or tributyltin. In the nuclear technique, apoptotic cells appeared
      as a single population containing reduced DNA content, while in the cellular
      techniques, apoptotic cells appeared as two or more subpopulations exhibiting
      increased fluorescence. Of these subpopulations, early apoptotic cells [which
      excluded propidium iodide (PI), indicating maintenance of membrane integrity]
      exhibited higher fluorescence but the same level of axial light loss (i.e.,
      size/refractive index) as viable cells; late apoptotic and dead cells (which
      incorporated PI) exhibited decreased axial light loss. However, while the Hoechst
      dyes allowed discrimination of late apoptotic from dead cells, CF did not. In
      comparing sensitivity to staining conditions, Hoechst 33258 fluorescence was the
      most stable over time, Hoechst 33342 the least, and CF fluorescence not only
      varied with time, but with tri-n-butyltin methoxide concentration. Comparison of
      single-parameter analyses revealed that axial light loss was sensitive only to
      late apoptotic changes; nuclear fluorescence was a better indicator of apoptotic
      subpopulations, but still underestimated the total percentage of affected cells,
      and Hoechst 33342 distinguished early apoptotic cells as those with elevated
      fluorescence. Early apoptotic cells stained with Hoechst 33258 also exhibited
      increased fluorescence, but could not be distinguished from late apoptotic and
      dead cells without a second parameter. These findings indicate that of the
      methods investigated, the method of choice for detecting apoptosis depends on the
      goal of analysis: Hoechst 33258 was best for discriminating apoptotic
      subpopulations, and CF was best for assessing alterations of membrane fluidity.
      For single-parameter analyses, Hoechst 33258 was best for determining the total
      percentage of affected cells, while Hoechst 33342 could be used to determine the
      percentage in early apoptosis.

PMID- 7511540
TI  - Diagnostic value of direct examination of the protected specimen brush in
      ventilator-associated pneumonia.
AB  - Interpretation of the protected specimen brush (PSB) technique is based on
      quantitative bacterial cultures (QC), which unfortunately requires at least 24 h.
      We prospectively compared the diagnostic value of direct examination (DE) and QC
      of PSB specimens in 75 patients with suspected pneumonia. We also determined the
      optimal technique for DE. QC was performed using the serial dilution technique.
      From the original suspension, two cytospin slides were obtained and stained by
      the May-Grunwald Giemsa (MGG) and the Gram method for DE. If the prescreening on
      the MGG-stained slide was positive, the morphology and the Gram staining of the
      organisms were assessed on the Gram-stained slide. Using the 10(3) colony forming
      units (cfu.ml-1) threshold for defining PSB as positive or negative, DE had a
      sensitivity of 85% and a specificity of 94%. In a parallel in vitro study, 18
      pairs of PSB specimens were collected from respiratory secretions inoculated with
      S. aureus. From each pair, one brush was processed as described above and the
      other was smeared on a glass slide prior to performance of QC. Using direct smear
      instead of cytocentrifuged preparation, slightly but significantly affected QC.
      Direct examination of cytospin slides is highly predictive of quantitative
      bacterial culture results, and provides rapid information regarding the Gram
      stain morphology of the causative organisms. It may therefore guide initial
      therapy.

PMID- 7511541
TI  - The primary structure of two chlorosome proteins from Chloroflexus aurantiacus.
AB  - The complete nucleotide sequence of two chlorosome proteins with apparent
      molecular weights of M(r) 18,000 and M(r) 11,000 from Chloroflexus aurantiacus
      have been determined. The two polypeptides were 145 and 97 amino acids long and
      possessed true molecular masses of 15,545 and 10,820 Da, respectively. Protein
      chemical sequencing was done in parallel to confirm the primary structure deduced
      from nucleotide sequencing. By Northern blot analysis of RNA isolated from
      phototrophically grown cells a transcript of 0.95 kb was detected which is the
      expected length for a mRNA encoding both genes.

PMID- 7511542
TI  - Synthesis and characterization of sapecin and sapecin B.
AB  - Two insect defencins, sapecin and sapecin B, were chemically synthesized to
      confirm their structure and antibacterial activity and also to examine the
      possibility that these peptides bind to the same site on the large conductance
      calcium-activated potassium channel as charybdotoxin. Both synthetic peptides
      showed the same antibacterial activity as native sapecins, indicating that the
      synthetic peptides folded correctly in the chemical synthesis. Synthetic sapecins
      did not show an inhibitory effect on [125I]charybdotoxin binding to rat brain
      synaptic membranes, suggesting that sapecin B recognizes a different binding site
      from that of charybdotoxin despite the similar structural motif.

PMID- 7511543
TI  - Growth factors and HIV-infection in children.
AB  - Three children with acquired immunodeficiency syndrome (AIDS) and chronic anaemia
      and leucopenia were treated with 5 micrograms/kg recombinant granulocyte colony
      stimulating factor subcutaneously three times a week and 50 IU/kg erythropoietin
      subcutaneously twice a week. The therapy was not interrupted during the follow-up
      period. All children showed an increase of leukocyte count and haemoglobin
      levels. No transfusion was necessary and the number of admissions into hospital
      fell. These results suggest that combined therapy with granulocyte colony
      stimulating factor and erythropoietin may improve leukopenia and anaemia, which
      is not zidovudine-related, in children who have AIDS.

PMID- 7511544
TI  - Insulin-like growth factor binding proteins in the human adrenal gland.
AB  - Insulin-like growth factors (IGFs) are thought to be important regulators of
      adrenocortical growth and steroidogenesis. IGFs are usually complexed with a
      family of specific IGF-binding proteins (IGFBPs) in serum, other body fluids, and
      in conditioned media of a variety of cell types. IGFBPs may either inhibit or
      potentiate the effects of IGFs. In the present study we have investigated the
      gene expression of the IGFBPs and IGF receptors in human fetal (HFA) and adult
      (HAA) adrenals. Northern blotting and/or reverse transcription polymerase chain
      reaction (RT-PCR) methods were used. IGFBP secretion into the cell culture medium
      was studied in primary cell cultures by Western ligand blotting and by
      radioimmunoassays. IGFBP-1 mRNA expression was low in adrenals: Northern blots
      were negative, but RT-PCR revealed IGFBP-1 mRNA in HFA. IGFBP-2 mRNA was equally
      expressed in both HFA and HAA with no differences in signal intensities by
      Northern blotting. IGFBP-3 mRNA was detected in HFA but not in HAA by Northern
      blotting. IGFBP-4 mRNA was expressed equally in both HFA and HAA. IGFBP-5 and -6
      mRNA expression was more abundant in HAA than in HFA. IGF-I and type I and type
      II IGF receptor mRNAs were equally expressed in both HFA and HAA. 12-O
      tetradecanoyl phorbol-13-acetate (TPA), a protein kinase regulator, upregulated
      IGFBP-1 in HFA cultures as determined by RIA, but ACTH was without effect. IGFBP
      2 was not regulated by TPA or ACTH neither at protein nor at mRNA level. IGFBP-3
      was downregulated by TPA both at protein and mRNA levels, but it was not affected
      by ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511545
TI  - Region-specific anti-thyroid hormone receptor (TR) antibodies detect changes in
      TR structure due to ligand-binding and dimerization.
AB  - There are multiple factors that potentially can induce structural changes in DNA
      bound thyroid hormone receptors (TRs) including protein-protein interactions,
      ligand-binding to TRs, and the thyroid hormone response element (TRE) sequence.
      We used a battery of anti-TR antibodies that recognize the amino-terminal, hinge,
      or carboxy-terminal regions of TRs to study changes in the epitope regions of in
      vitro translated TRs in electrophoretic mobility shift assays. We found that the
      carboxy-terminal and hinge region antibodies recognized TR homodimers but not
      TR/T3-receptor auxiliary protein or TR/retinoid X receptor heterodimers. The
      amino-terminal antibodies detected conformational changes due to ligand binding.
      In contrast, each antibody recognized TR complexes bound to TREs containing half
      sites arranged in three different orientations. These results suggest that
      dimerization with nuclear proteins and ligand-binding, rather than the
      orientation of TRE half-sites, cause changes in several TR subregions.

PMID- 7511546
TI  - Functional effects of transgenic expression of cholera toxin in pancreatic beta
      cells.
AB  - Investigation of intracellular pathways of stimulus-secretion signaling in vivo
      is possible by transgenic expression of agents known to influence specific
      biochemical interactions in the cells. The objective of the present study was to
      establish an experimental model for analyzing signal transduction mechanisms in
      pancreatic beta-cells in vivo, by expressing the cholera toxin A1 subunit under
      control of the insulin promoter, intending a constant activation of the Gs
      protein, and thereby constant generation of cAMP. Surprisingly, the transgenic
      mice demonstrated mild hyperglycemia and hypoinsulinemia in vivo, and diminished
      glucose-induced insulin release from the in vitro perfused pancreas, whereas the
      pancreatic insulin content was normal. These observations suggest a deficiency in
      either the insulin release mechanisms or glucose recognition. Although the
      translated cholera toxin A1 subunit was biologically active, there was no
      increase in the islet content of cAMP. We conclude that the observed phenotype in
      the cholera toxin transgenic mice may be caused by a deleterious effect of the
      transgene itself on beta-cell function, or that counter regulatory mechanisms may
      compensate for the transgene-induced changes in intracellular enzymatic pathways.

PMID- 7511547
TI  - Terminal differentiation of mouse preadipocyte cells: adipogenic and
      antimitogenic role of triiodothyronine.
AB  - The role of triiodothyronine (T3) in the differentiation process of Ob1771 mouse
      preadipocyte cells has been studied under serum-free and hormone supplemented
      culture conditions which were previously shown to lead to terminal
      differentiation. In the absence of T3, a dramatic decrease in the adipogenic
      activity of the culture medium (EC50 = 0.1 nM) could be observed, as indicated 12
      days after confluence by the low levels of late markers of differentiation such
      as adipsin, lipid-binding protein aP2 and glycerol-3-phosphate dehydrogenase as
      well as the sharp reduction of the number of triacyglycerol-containing cells.
      This decrease in adipogenic activity was accompanied by a parallel increase of
      the mitogenic potency of the culture medium. Therefore, T3 appears to be a
      hormone capable of modulating both proliferation and differentiation of
      preadipocytes. T3 ceased to be necessary provided the culture medium was
      supplemented with high concentrations of inducers of differentiation, such as 8
      bromo-cAMP or carbaprostacyclin.

PMID- 7511548
TI  - Lineage-specific and differentiation-dependent expression of K12 keratin in
      rabbit corneal/limbal epithelial cells: cDNA cloning and northern blot analysis.
AB  - Corneal epithelial cells synthesize an acidic (55 kDa) K12 and a basic (64 kDa)
      K3 keratin as their major differentiation products during an advanced stage of
      differentiation. In this paper, we describe the cDNA cloning of rabbit K12
      keratin. We used a 36 base pairs (bp) oligonucleotide corresponding to a
      consensus sequence of many known acidic keratins as a probe to screen a cDNA
      library of normal rabbit corneal epithelium. Several partial cDNA clones were
      isolated. Hybrid-selection showed that the 3'keratin chain-specific portion of
      the cDNA hybridizes with K12 mRNA. A rabbit antiserum raised against the C
      terminus of the cDNA-deduced amino acid sequence recognizes, in immunoblotting,
      the K12 keratin. In situ hybridization showed that K12 mRNA is present in all
      cell layers of central corneal epithelium, but in only the suprabasal cells of
      limbal epithelium indicating a parallel expression pattern between K12 and K3.
      Cultured rabbit corneal epithelial cells initially synthesize K14/K5 keratins,
      but later when the cells become heavily stratified they synthesize large
      quantities of K12 and K3 mRNAs, as detected by Northern blotting. Cultured
      esophageal epithelial cells do not make K12 mRNA confirming the tissue
      specificity of K12 expression. Although it has been suggested that conjunctival
      epithelial cells can trans-differentiate into a bona fide corneal epithelium, we
      showed here that cultured conjunctival cells do not synthesize significant
      amounts of K12/K3 mRNAs. These results strongly suggest that conjunctival
      epithelial cells, whose differentiation can be modulated significantly by the
      extracellular matrix, form a lineage intrinsically distinct from the
      corneal/limbal epithelial lineage.

PMID- 7511549
TI  - Molecular characterization of the body site-specific human epidermal cytokeratin
      9: cDNA cloning, amino acid sequence, and tissue specificity of gene expression.

PMID- 7511550
TI  - Molecular analysis of anti-DNA antibodies.
AB  - There are two major reasons for interest in antibodies to DNA: autoantibodies to
      DNA are characteristic of the autoimmune disease systemic lupus erythematosus and
      contribute to its pathology; and both autoantibodies and experimentally induced
      antibodies to nucleic acids serve as useful biochemical reagents. Physical
      biochemistry and molecular biology are applied increasingly to questions of the
      structure and origin of antibodies to DNA and how antibodies recognize specific
      structures in DNA. Cloning of cDNA for Ig V regions of anti-DNA antibodies
      reveals that some cells making IgG disease-related autoantibodies are derived
      from precursor cells that produce natural autoantibodies unrelated to disease. In
      addition, some immunization-induced antibodies to DNA use gene segments similar
      to those found in autoantibodies. Cloning and expression of recombinant V regions
      allow detailed analysis of antibody structures required for DNA binding. Domain
      swapping and mutagenesis with vectors for bacterial expression of single chain Fv
      molecules revealed the importance of CDR3 sites of both H and L chain V regions
      for specific antigen binding by antibody to Z-DNA. In certain autoantibodies, the
      H chain plays a dominant role in determining DNA binding. Molecular analysis
      opens doors to studies of normal immune tolerance and its loss in autoimmune
      disease as well as to development of antibodies with modified specificity.

PMID- 7511551
TI  - Distinguishing between acute and symptomatic chronic hepatitis B virus infection.
AB  - BACKGROUND/AIMS: Differentiating between an acute hepatitis B (AH-B) infection
      and an acute exacerbation of a chronic hepatitis B (CH-B) infection can present a
      problem for the clinician. The only current serological method of distinguishing
      between acute and symptomatic chronic hepatitis B virus (HBV) infection is the
      immunoglobulin M antibody to hepatitis B core antigen (anti-HBc) assay, which can
      be problematic. Therefore, in an attempt to better distinguish between acute and
      chronic HBV infection, sera from 26 patients with AH-B and 53 patients with CH-B
      were compared in a variety of experimental immunoassays. METHODS: Experimental
      assays have been designed to detect free antibody to hepatitis B e antigen (anti
      HBe), hepatitis B e antigen (HBeAg)/anti-HBe immune complexes (ICs), and
      hepatitis B surface antigens (HBsAg)/antibody to hepatitis B surface antigen
      (anti-HBs) in the presence of excess antigen. An additional assay was developed
      to detect a novel anti-HBc specificity, designated antibody to woodchuck
      hepatitis virus (anti-HBcW), which cross-reacts with the core antigen of the
      woodchuck hepatitis virus. RESULTS: Sera from patients with CH-B showed
      significantly higher levels of free anti-HBe, HBeAg/anti-HBe ICs, and HBsAg/anti
      HBs ICs compared with AH-B patient sera. Furthermore, patients with CH-B
      consistently produced high titer anti-HBcW, whereas patients with AH-B produced
      little or no anti-HBcW antibody. CONCLUSIONS: The serology of AH-B infection and
      symptomatic CH-B infection can be distinguished using a variety of experimental
      immunoassays in addition to the immunoglobulin M anti-HBc assay.

PMID- 7511553
TI  - Local secretion of corticotropin-releasing hormone by enterochromaffin cells in
      human colon.
AB  - BACKGROUND/AIMS: Corticotropin-releasing hormone (CRH) is a regulator of the
      hypothalamic-pituitary-adrenal axis and a coordinator of the gastrointestinal
      response to stress. In addition to its central effects, CRH has peripheral
      effects on the immune system. CRH is present in several human tissues, such as
      the brain, spinal cord, adrenal medulla, lung, liver, peripheral blood
      leukocytes, as well as the gastrointestinal tract. The current study examined the
      local production of CRH in the normal human colon. METHODS: Normal human colonic
      tissues obtained by endoscopic biopsy were immunostained with anti-CRH and anti-5
      hydroxytryptamine antibody and analyzed for CRH messenger (m)RNA by a reverse
      transcribed polymerase chain reaction method and by in situ hybridization.
      RESULTS: Immunoreactive CRH and CRH mRNA were detected in the colonic mucosal
      cells in the neighborhood of the base of the crypts. The mucosal cells that
      expressed CRH mRNA also immunostained with anti-5-hydroxytryptamine antibody.
      CONCLUSIONS: Normal human colonic mucosal enterochromaffin cells produce CRH. CRH
      in the colonic mucosa may play a role in the modulation of the intestinal immune
      system and/or other gastrointestinal functions basally during stressful
      conditions.

PMID- 7511552
TI  - A new, effective, and safe therapeutic option using proton irradiation for
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Conventional radiation is almost useless for hepatocellular
      carcinoma (HCC) because of the severe adverse effects of the irradiation to the
      accompanying liver cirrhosis. In contrast, the proton beam has Bragg peak, which
      limits distribution of the beam. The aim of this study was to prove the
      usefulness of proton irradiation for HCC. METHODS: The proton irradiation was
      performed in 32 nodular lesions in 24 patients with HCC who had unresectable
      tumors or serious complications; the proton irradiation was performed either as
      monotherapy (15 lesions) or as combination therapy to insufficient Lipiodol
      targeted chemotherapy (Kodama Co. Ltd., Tokyo, Japan) (17 lesions). The energy
      was 250 MeV, and 50-87 Gy (76.5 +/- 9.5, mean +/- SD) in total was irradiated for
      a time period of 17-69 days. RESULTS: After 1 year, size reduction was seen in 12
      out of 13 lesions (92%) in the monotherapy group and 9 out of 9 lesions (100%) in
      the combination therapy group; after 2 years, size reduction was seen 4 out of 5
      lesions (80%) in the monotherapy group and 5 out of 5 lesions (100%) in the
      combination therapy group. Local tumor control has being assured for 2 years of
      the observation, which is continuing for another 2 years. None of the patients
      have experienced any serious adverse effects. CONCLUSIONS: These results show
      that proton irradiation is a new, safe, and effective therapeutic option in cases
      of HCC, even in patients with unresectable tumors or those with serious
      complications.

PMID- 7511554
TI  - Rectal epithelial expression of protein kinase A phosphorylation of cystic
      fibrosis transmembrane conductance regulator.
AB  - BACKGROUND/AIMS: Human rectal epithelium in cystic fibrosis (CF) shows impaired
      ion transport in response to theophylline or bethanechol, although it possesses
      regulatory subunits of adenosine cyclic 3',5'-monophosphate (cAMP)-dependent
      protein kinase (protein kinase A). Protein kinase A-specific phosphorylation of
      CF transmembrane conductance regulator (CFTR) in rectal tissues of control and CF
      volunteers was examined in this study. METHODS: CFTR was evaluated using a
      polyclonal antiserum (pre-NBF) raised against a peptide corresponding to residues
      415-427 of CFTR. Microsomal membranes from normal and CF rectal mucosa and from T
      84 cells were incubated with [gamma 32P]-adenosine triphosphate +/- protein
      kinase A and subjected to immunoblotting with pre-NBF and autoradiography.
      RESULTS: Pre-NBF recognized a single band of 180 kilodaltons. Protein kinase A
      altered phosphorylation of this 180-kilodalton band 1.4-, 2.2- and 0.9-fold in T
      84, normal, and CF rectal membranes, respectively. Catalytic activities of
      protein kinase A, Ca2+ calmodulin protein kinase, or protein kinase C in control
      and CF tissues were similar. CONCLUSIONS: cAMP and Ca(2+)-signaling pathways are
      normal up to the kinases in CF rectal mucosa. Our results suggest differences in
      CFTR phosphorylation in normal and CF rectal mucosal membranes.

PMID- 7511555
TI  - [Detection of antibodies to hepatitis C virus in blood donors].
AB  - The study was aimed at assessment of prevalence of antibodies to hepatitis C
      virus (anti-HCV) among donors. Blood sera were tested for anti-HCV, alanine
      aminotransferase (ALT), and bilirubin in two groups of donors. Group 1 were men
      belonging to organized collective bodies, mean age 20 years, permanent residents
      of Russia and CIS countries (n = 6157), group 2 were donors of both sexes, mean
      age 37, 70% men and 30% women, residents of Moscow (n = 1810). Incidence of anti
      HCV in group 1 was 1.4%, in group 2 2.5%. ALT levels were elevated vs. the norm
      by 2.2% in group 2 but in only 4 of these subjects anti-HCV were detected.
      Bilirubin level was increased in 0.28% of group 1 subjects and in 2.8% of group 2
      ones, none of these examinees having anti-HCV. The share of anti-HCV carriers
      increases with age. Screening for ALT and bilirubin cannot be a substitute for
      donor blood testing for anti-HCV.

PMID- 7511556
TI  - [Transcatheter embolization of the internal iliac arteries as an alternative to
      their surgical ligation].
AB  - Embolization of internal iliac arteries was performed in a patient with
      haemorrhage from advanced uterine cervix cancer. Apart from surgical ligation of
      arteries, embolization is sometimes the only form of palliative treatment which
      in many cases improves the general condition of patients and allows continuation
      anticancer management. As it diminishes the fear of recurrent haemorrhages
      embolization significantly improves also the psychological state of patients.

PMID- 7511557
TI  - Modulation of cytokine expression by cAMP analogs in myc-immortalized microglial
      cell lines.
AB  - Expression of cytokines can be modulated by cAMP in macrophages or in primary
      microglial cultures. Similar to what is observed in normal conditions, treatment
      of immortal microglial cell lines with dibutyryl-cAMP blocked the accumulation of
      TNF alpha transcripts induced by lipopolysaccharide, whereas activation of
      Interleukin-1 alpha (IL-1 alpha) remained unaffected. Immortalized cell lines can
      therefore be regarded as a valid model to test the immune responsiveness of
      microglial cells in the presence of neuro-endocrine agents modulating cAMP
      levels.

PMID- 7511558
TI  - [Pharmacological study of ebastine, a novel histamine H1-receptor antagonist].
AB  - The anti-allergic activity of ebastine, a novel antihistamine, was assessed in
      comparison with several antihistamines. 1) Orally administered ebastine dose
      dependently inhibited 7-day homologous passive cutaneous anaphylaxis (PCA),
      experimental allergic rhinitis and experimental asthma in guinea pigs or rats
      (ED50-values were 2.17, 0.29 and 0.35 mg/kg, respectively); and its anti-allergic
      activity was more potent than those of terfenadine and mequitazine. Moreover, its
      PCA-inhibitory activity was still observed 24 hr after the administration. 2)
      Orally administered ebastine also inhibited histamine-induced skin reaction in
      rats (ED50: 1.10 mg/kg). 3) In isolated guinea pig trachea, ebastine had no
      effect on histamine-induced contraction, but carebastine, a main metabolite of
      ebastine, inhibited this contraction (IC50: 0.12 microM). 4) Carebastine (30-100
      microM) suppressed the histamine release from rat peritoneal mast cells and human
      basophils. 5) Ebastine at a high oral dose showed slight inhibition of the
      specific binding of 3H-mepyramine to the histamine H1-receptor in rat brain. This
      binding-inhibitory activity of ebastine was little more potent than that of
      terfenadine, but much less potent than those of mequitazine and ketotifen. These
      results indicated that ebastine has potent and long acting anti-allergic activity
      with few side effects based on the antihistaminic activity in the central nervous
      system. Furthermore, it was suggested that these effects of ebastine are due to
      the action of a main metabolite, carebastine.

PMID- 7511559
TI  - The distribution of adhesion molecules in chronic periaortitis.
AB  - Chronic periaortitis is a local complication of human atherosclerosis. It is
      defined as the triad of advanced atherosclerosis, medical thinning and aortic
      adventitial chronic inflammation. It is present to a variable degree in
      association with atherosclerotic abdominal aortic aneurysms. These aortic
      adventitial infiltrates differ from those described solely within the atheroma
      itself, in that they consist predominantly of B lymphocytes. Many of the
      lymphocytes are activated and proliferating, and germinal centres are common. In
      this study, an immunohistochemical analysis was carried out on fresh surgical
      aortic aneurysm tissue in order to investigate the presence and distribution of
      activation-inducible adhesion molecules, and to correlate this with the degree of
      inflammation. A consistent finding was the presence of E-selectin on endothelial
      cells in up to 50% of the vessels throughout the aortic wall and at the base of
      the atheroma, independent of the severity of inflammation. ICAM-1 expression was
      abundant on many cell types and increased with the severity of chronic
      inflammation, being strongest in the germinal centres. VCAM-1 expression was
      predominant on follicular dendritic cells and also increased with severity of
      inflammation. VCAM-1 expression was also detected on vessels within lymphoid
      follicles. The pattern of expression of the adhesion molecules suggests a role in
      the initiation and progression of chronic inflammation associated with advanced
      atherosclerosis.

PMID- 7511560
TI  - The extracellular matrix in pigmented skin lesions: an immunohistochemical study.
AB  - In recent years the interaction between tumour cells and the surrounding
      extracellular matrix in the process of tumour development, invasion and
      metastasis has been a focus of interest. We studied frozen sections of nine
      naevocellular naevi (junctional, compound and intradermal), 40 dysplastic naevi,
      six pagetoid in situ melanomas and 12 superficial spreading melanomas in order to
      determine the expression of: the basement membrane proteins collagen type IV and
      laminin, the interstitial collagen types I, III and VI, and fibronectin and
      tenascin. An indirect immunoperoxidase technique was used. In the various stages
      of melanocytic tumour progression we observed: 1 loss of type IV collagen and
      laminin within dermal melanocytic cell nests; 2 de novo expression of basement
      membrane type IV collagen and increased expression of the interstitial collagen
      types I, III and VI, as well as tenascin and fibronectin in the dermal stroma
      surrounding dysplastic naevus cells and melanoma cells; 3 presence of
      extracellular matrix components in close association with intra-epidermally
      located invading atypical melanocytes. These data demonstrate the complex
      alterations of the composition of the extracellular matrix from bland naevi
      through lesions with progressive atypia to invasive melanoma. The changes
      described result in a molecular environment which melanocytes with an altered
      adhesion molecule profile are able to invade.

PMID- 7511561
TI  - Solid cell nests of the thyroid in medullary thyroid carcinoma.
AB  - Solid cell nests of the thyroid gland were studied in 44 patients with medullary
      thyroid carcinoma. In 10 (22.7%) patients, solid cell nests were revealed in the
      vicinity of tumour foci (five cases) or in the contralateral thyroid lobe and
      isthmus (four cases); in one case the location was indeterminate. In all seven
      cases in which immunohistochemical studies were carried out, solid cell nests
      showed negative staining for thyroglobulin, calcitonin and chromogranin A,
      findings which were distinct from those in medullary thyroid carcinoma. It is
      therefore suggested that solid cell nests of the thyroid are not precursors of
      this tumour.

PMID- 7511562
TI  - Potential role for non-HLA-restricted cytotoxic cells in the immune surveillance
      of acute leukemia.
AB  - The observation of more frequent leukemias in immune deficiencies of the non-HLA
      restricted cytotoxic cell system and the participation of this system in the anti
      leukemic effect of allogeneic bone marrow transplantation in acute leukemia
      indicate that these cells might play a role in the immune surveillance against
      leukemia. In order to find more direct evidence of this role we studied the
      susceptibility of leukemic cells to lysis by non-HLA-restricted cytotoxic cells,
      the functional value of these cells in leukemic patients in complete remission
      (CR), and expression by leukemic cells of adhesion molecules CD54 and CD58, which
      play a role in the adherence between cytotoxic cells and their targets. Our
      results are concordant to confirm a potential role of non-HLA-restricted
      cytotoxic cells in the immune surveillance of acute leukemia based on increased
      relapse rate in acute myeloid leukemia patients with no inducible lymphokine
      activated killer (LAK) cell activity during CR, short survival of acute
      lymphoblastic leukemia patients whose blast cells are resistant to lysis by LAK
      cells, and poor overall prognosis of leukemias which do not express CD58.

PMID- 7511563
TI  - Suppression of natural killer cell activity by granulocytes in patients with
      aplastic anemia: role of granulocyte colony-stimulating factor.
AB  - Patients with aplastic anemia were tested for natural killer (NK) activity, and
      the roles of granulocytes and granulocyte colony-stimulating factor (G-CSF) in
      the regulation of cytotoxicity were evaluated. Blood lymphocytes showed low or no
      NK activity against K562 targets. The depression of NK activity was more
      frequently recorded for patients who were not in remission and those who received
      G-CSF administration. Granulocytes of aplastic anemia patients with impaired NK
      activity suppressed the lytic activity of NK cells. By contrast, granulocytes
      from normal controls and aplastic anemia patients with normal NK activity had no
      suppressive activity. There was a good correlation between NK activity of
      lymphocytes and suppressive activity of granulocytes. Blocking of direct contact
      of suppressor and effector cells by cell chambers abolished suppression of
      cytotoxicity. NK suppression by granulocytes was resistant to treatment with
      catalase or superoxide dismutase. In vitro stimulation with G-CSF of granulocytes
      that naturally had no suppressive activity resulted in development of suppressive
      function, whereas granulocytes with natural suppressive activity were not further
      stimulated in vitro by G-CSF to express augmented activity. These results suggest
      that the presence of suppressor granulocytes in the blood could be one cause of
      the impaired NK activity in patients with aplastic anemia.

PMID- 7511564
TI  - Induction of hypersensitivity to endotoxin in C3H/HeJ mice by immunization with L
      form Salmonella typhimurium.
AB  - When endotoxin low-responder C3H/HeJ mice were immunized with L-form Salmonella
      typhimurium, the mice were more susceptible to a lethal challenge with S.
      typhimurium 1 week after immunization (1-week mice) than were the unimmunized
      controls. One-week immune mice produced overwhelming amounts of tumor necrosis
      factor-alpha (TNF-alpha) in the blood after infection, while 4-week immune mice
      produced lesser amounts of this cytokine with a 75% survival rate at 60 days
      postinfection. Pretreatment with anti-TNF-alpha antibody prevented 1-week immune
      mice from succumbing to acute illness. Endotoxin-stimulated peritoneal
      macrophages from 1-week immune mice produced higher amounts of TNF-alpha in vitro
      than did those from 4-week immune mice and they expressed larger amounts of TNF
      alpha mRNA on Northern blot. The capacity of macrophages to produce TNF-alpha in
      vitro was correlated with the degree of colonization by the L form in the cells.
      These results suggest that the colonization by L-form S. typhimurium in
      macrophages alters the susceptibility to S. typhimurium of C3H/HeJ mice and that
      TNF-alpha might play a major role in this alteration of host resistance.

PMID- 7511565
TI  - T lymphocytes from human chimeras do recognize antigen in the context of
      allogeneic determinants of the major histocompatibility complex.
AB  - Human stem cells from the fetal liver can be transplanted to immunodeficient
      patients and reconstitute their immunity by giving rise to immunocompetent T
      lymphocytes of donor origin. Despite full HLA mismatch between donor and host,
      the helper T cells and the cytotoxic T cells which develop in these chimeric
      patients are totally functional. They recognize the antigenic peptides presented
      in the context of the foreign HLA molecules of the recipient, indicating that
      donor stem cells have been positively selected in the host environment, probably
      the thymic epithelial cells. By contrast, negative selection appears to be
      imposed upon T cells by donor hemopoietic cells, probably macrophages or
      dendritic cells, migrating from the transplant to the host thymus. Clonal
      deletion is then responsible for tolerance to donor HLA antigens, while clonal
      anergy explains tolerance to host HLA antigens.

PMID- 7511566
TI  - Characterisation of putative monoclonal anti-G3m(u) and anti-G3m(g) reagents and
      their antigenic determinants.
AB  - Monoclonal antibodies (MAbs) against IgG3 allotypic markers were evaluated in
      haemagglutination inhibition and IgG3 capture ELISA. MAbs PNF69C and 200D1
      exhibited G3m(u) and G3m(g) specificity respectively. In HAI target epitopes
      detected by MAbs were remarkably stable to physiochemical degradation. Western
      blotting revealed that MAb 200D1, bound to intact IgG3 heavy chain disease
      protein and not its pFc' fragment; a result consistent with the CH2 domain
      location of the G3m(g) allotope. The G3m(u) allotope is also located within this
      domain. Surprisingly anti-G3m(u) MAb PNF69C bound to the pFc' of IgG3-related
      protein, HW, and to the pFc' of IgG1-related protein, PR, in Western blot.

PMID- 7511567
TI  - A speculative view of immune recognition.
AB  - The speculation that immunologically reactive haptens must be those attached to
      carriers' immunodominant epitopes suggests a clearer mechanism by which the
      mysterious hapten-carrier phenomena are generated. This review focuses on the
      molecular biological nature of immune recognition of hapten-protein antigens both
      by the T-cell and the B-cell. T and B lymphocytes specifically recognize one
      determinant of the same antigen molecule in two different ways and in different
      circumstances. The B-cell recognizes an antigen by the preliminary antigen
      receptors on the cell's surface, at the time it is still intact, interiorizes it
      and presents the processed antigenic peptide after an antigen processing
      procedure. In contrast, the T-cell recognizes a hidden antigenic determinant,
      together with portions of the MHC on the presenting cell. The immune memory is
      mainly directed to the hidden internal determinant of an antigen. Some aspects of
      the clonal selection theory of antibody formation are also discussed at the
      modern molecular level.

PMID- 7511569
TI  - Smooth muscle cell responsiveness to nitrovasodilators in hypertensive and
      normotensive rats.
AB  - Endothelium-derived relaxing factor and exogenous nitrovasodilators are thought
      to produce smooth muscle relaxation by activation of soluble guanylate cyclase.
      To investigate whether diminished cyclic GMP (cGMP) accumulation underlies the
      differences in vascular reactivity to nitrovasodilators between Wistar-Kyoto
      (WKY) rats and spontaneously hypertensive rats (SHR), we determined cGMP
      formation in aortic smooth muscle cells from the two strains. Both cultured cells
      and aortic rings from 12- to 14-week-old SHR accumulated greater amounts of cGMP
      on stimulation with exogenous nitrovasodilators (ie, sodium nitroprusside) than
      those from WKY rats, whereas there was no difference observed in cells from
      prehypertensive animals (5- to 6-week old) between the two strains.
      Responsiveness of smooth muscle cells to endothelium-derived relaxing factor was
      investigated in cocultures of bovine aortic endothelial cells (BAE) and smooth
      muscle cells from SHR and WKY rats. cGMP accumulation elicited by endothelium
      derived relaxing factor released either basally or in response to bradykinin and
      the calcium ionophore A23187 was greater in smooth muscle from 12- to 14-week-old
      SHR than from age-matched WKY rats (80 +/- 17 versus 11 +/- 2 for basal; 152 +/-
      12 versus 80 +/- 26 for A23187; 163 +/- 21 versus 40 +/- 12 pmol/mg protein per
      15 minutes for bradykinin) in SHR/BAE and WKY/BAE cocultures, respectively.
      Northern blot analysis of steady-state messenger RNA levels for the beta 1
      subunit of soluble guanylate cyclase revealed higher levels of the message in
      SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511568
TI  - Parathyroid hormone/adenylate cyclase coupling in vascular smooth muscle cells.
AB  - Parathyroid hormone (PTH) has been implicated in hypertension, but PTH infusion
      results in vasodilation. PTH activates adenylate cyclase in vascular smooth
      muscle, but little is known about the factors that regulate PTH
      receptor/adenylate cyclase coupling in vascular cells. To characterize hormone
      receptor signaling, we measured cyclic AMP levels in rat arterial smooth muscle
      cells in culture exposed to PTH (bovine 1-34). PTH yielded time- and
      concentration-dependent increases in cyclic AMP levels. Compared with
      isoproterenol, PTH was more potent, with a threshold at 2 x 10(-9) versus 5 x 10(
      8) mol/L and half maximal responses at 10(-8) versus 2.4 x 10(-7) mol/L. PTH
      induced increases in cyclic AMP were independent of extracellular calcium,
      cyclooxygenase metabolites, phospholipase C, and protein kinase C because PTH
      induced increases in cyclic AMP were not prevented by variations in extracellular
      calcium, indomethacin, angiotensin II, vasopressin, and protein kinase C
      activators or inhibitors. PTH/adenylate cyclase coupling was G protein-dependent
      because increases in cyclic AMP were prevented by preincubation with cholera
      toxin but not with pertussis toxin. Prolonged exposure to PTH resulted in time-
      and concentration-dependent homologous desensitization of cyclic AMP responses.
      Desensitization occurred proximal to G protein/adenylate cyclase because after
      prolonged PTH, responses to forskolin and cholera toxin remained intact.
      Desensitization was independent of protein kinase A and receptor sequestration
      because cyclic AMP responses remained after prolonged exposure to forskolin and
      pretreatment with phenylarsine oxide, colchicine, and cytochalasin D. We conclude
      that in vascular smooth muscle cells, PTH is coupled to adenylate cyclase through
      a cholera toxin-sensitive G protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511571
TI  - [Non-pharmacologic procedures in pain therapy].

PMID- 7511570
TI  - Selectin-P-mediated adherence of platelets to neutrophils is regulated by
      prostanoids and nitric oxide.
AB  - The expression of Selectin-P was measured in terms of formation of "rosettes" by
      human gel-filtrated thrombin (30-50 mU)-stimulated platelets on the surface of
      isolated homologous neutrophilic leucocytes (PMNs) according to Jungi (1986). The
      monoclonal anti-Selectin-P antibody completely prevented the formation of
      "rosettes", proving the specificity of Selectin-P-mediated adhesion. The Selectin
      P-mediated adhesion of platelets to PMNs was inhibited by both iloprost (ILO)
      (IC50 = 5.0 nM) and sodium nitroprusside (NaNP) (IC50 = 0.93 microM); thus ILO is
      ca. 180 times more potent an inhibitor of "rosette" formation than NaNP. The NOS
      inhibitors L-NO2Arg (10-30 microM) and L-MetArg (3-30 microM) each suppressed the
      adhesion, while at lower and higher concentrations these NOS-inhibitors did not
      influence rosette formation. L-Arginine (up to 1 mM) was not able to influence
      significantly the Selectin-P-mediated adhesion of platelets to PMNs. The COX
      inhibitor aspirin (10-30 microM) promoted the adhesion. We conclude that the
      Selectin-P-mediated adhesion of platelets to PMNs is inhibited by both ILO and
      NaNP, whereas endogenous prostanoids and nitric oxide seem to exert an antagonist
      effect on the adhesion of platelets to PMNs.

PMID- 7511573
TI  - [Therapy of chronic viral hepatitis with interferon].

PMID- 7511574
TI  - Different clinicopathologic findings in two histologic types of carcinoma of
      papilla of Vater.
AB  - The aim of this study was to investigate the differences between the
      clinicopathological findings in two histologic types of carcinoma of the papilla
      of Vater. We histologically classified carcinoma of the papilla into two types:
      1) an intestinal type that resembles tubular adenocarcinoma of the stomach or
      colon, and 2) a pancreaticobiliary type that is characterized by papillary
      projections with scant fibrous cores. We examined 53 cases of resected carcinoma
      of the papilla. The intestinal-type carcinomas were similar to the intestinal
      mucosa in that they had lysozyme-containing, Paneth or argyrophil cells, as
      demonstrated by the immunohistochemically positive stainings for the anti
      lysozyme antibody. Although both the sizes of the two types of carcinomas and the
      age distributions of cases with the two types of carcinoma were almost the same,
      the prognosis of the cases with the intestinal type was much better than that of
      the cases with the pancreaticobiliary type. Histological lymph node metastasis
      was found significantly more often in the pancreaticobiliary type. This result
      was supported by the fact that small carcinomas of the intestinal type showed
      little or no invasion into the surrounding interstitium, as opposed to the
      pancreaticobiliary type, which had a strong infiltrative tendency. The
      pathogenesis of carcinoma of the papilla of Vater should be further evaluated,
      taking into consideration the existence of these two histologic types.

PMID- 7511572
TI  - [Pain therapy of arthrosis].

PMID- 7511576
TI  - Physiological aspects of disinfection resistance in Pseudomonas cepacia.
AB  - A Pseudomonas cepacia population was isolated which had reduced susceptibility to
      iodine and maintained resistance when subcultured several times in phosphate
      buffer. This population was also resistant to iodine after growth in a minimal
      medium containing glycerol but not glucose. Addition of cAMP to glucose-grown
      cells caused increased resistance to iodine. Iodine-resistant cultures also
      demonstrated reduced susceptibility to chlorination but not to heat or metals
      (Cu/Ag). The results indicate that halogen resistance can be expressed in varying
      degrees, dependent on the carbon source, and cAMP may promote this expression.
      Thus, a catabolite repression-like mechanism may cause resistant cultures grown
      in some media to become more sensitive to halogens.

PMID- 7511577
TI  - Effect of sub-MIC antibiotics on the cell surface and extracellular virulence
      determinants of Pseudomonas cepacia.
AB  - The effects of sub-MICs of ciprofloxacin and tobramycin on the cell surface
      characteristics and extracellular virulence factors of Pseudomonas cepacia were
      evaluated. Cells were grown in batch culture under iron-deficient and iron
      replete conditions. At sub-MIC levels that did not affect bacterial growth cell
      surface hydrophobicity decreased under both iron-replete and iron-depleted
      conditions with ciprofloxacin, but increased with tobramycin under iron
      sufficient conditions. Exopolysaccharide synthesis, lipase production and
      siderophore production were all significantly increased by the presence of
      ciprofloxacin under both growth conditions. Outer membrane protein and
      lipopolysaccharide profiles were not affected by exposure to the two antibiotics.

PMID- 7511578
TI  - The molecular basis of anti-retroviral therapy.

PMID- 7511575
TI  - Cyclosporin A enhances susceptibility of multi-drug resistant human cancer cells
      to anti-P-glycoprotein antibody-dependent cytotoxicity of monocytes, but not of
      lymphocytes.
AB  - Cyclosporin A (CsA) was previously found to bind to P-glycoprotein expressed on
      multidrug-resistant (MDR) cancer cells. In the present study, the effect of CsA
      on anti-P-glycoprotein monoclonal antibody (mAb)-dependent cell-mediated
      cytotoxicity (ADCC) against human MDR cells was examined. The ADCC reaction was
      assessed by 4-h 51Cr-release assay. Highly purified lymphocytes (> 99%) and
      monocytes (> 99%) obtained from blood mononuclear cells (MNC) of healthy donors
      were used as effector cells. CsA decreased the cytotoxic activity of MNC against
      MDR cells, but enhanced their ADCC activity in the presence of anti-P
      glycoprotein mAb MRK16. Lymphocyte-mediated ADCC and natural killer activity
      against MDR cells were also suppressed by addition of CsA. CsA induced a
      significant dose-dependent increase in monocyte-mediated ADCC activity.
      Interestingly, pretreatment of MDR cancer cells, but not of monocytes, with CsA
      significantly enhanced ADCC activity mediated by monocytes, but not by
      lymphocytes. A CsA analog (PSC833) and FK-506, but not verapamil also increased
      the sensitivity of MDR cells to ADCC by monocytes. CsA did not affect the binding
      of monocytes to MDR cells in the presence of MRK16 mAb. These results indicate
      that CsA may directly enhance the susceptibility of MDR cancer cells to the
      monocyte-mediated ADCC reaction.

PMID- 7511579
TI  - Mode of action of the cyclic depsipeptide antibiotic LL-AO341 beta 1 and partial
      characterization of a Staphylococcus aureus mutant resistant to the antibiotic.
AB  - The antibacterial activity of the cyclic antibiotic LL-AO341 beta 1 was examined.
      The antibiotic was a narrow spectrum agent, effective principally against Gram
      positive organisms. The intrinsic insusceptibility of Escherichia coli was due to
      exclusion of the drug by the outer membrane. The antibiotic was bactericidal
      against Staphylococcus aureus, and cell death was associated with lysis of the
      bacteria. The antibiotic did not specifically inhibit the synthesis of DNA, RNA,
      protein, lipid or peptidoglycan since these synthetic activities continued for
      several minutes after exposure to lethal concentrations of the antibiotic and
      then all abruptly ceased between about 8 and 15 minutes post antibiotic exposure.
      These results are consistent with the cytoplasmic membrane being the primary
      target for LL-AO341 beta 1. Mutants of S. aureus 8325-4 selected on 10- or 20
      times the MIC of LL-AO341 beta 1 occurred spontaneously with a frequency of about
      3 x 10(-6). A mutant expressing a 160-fold increase in the MIC of LL-AO341 beta 1
      was obtained by exposing cultures to progressively increasing concentrations of
      the antibiotic. This mutant displayed no cross-resistance to other agents apart
      from telomycin (a structural analogue of LL-AO341 beta 1), apparently did not
      modify or degrade LL-AO341 beta 1 and had only a slightly longer doubling time
      than the parent strain.

PMID- 7511580
TI  - Epitope mapping of Escherichia coli cell division protein FtsZ with monoclonal
      antibodies.
AB  - A fusion between lacZ and ftsZ of Escherichia coli was constructed to obtain a
      beta-galactosidase-FtsZ fusion protein. This fusion protein was used to raise
      antibodies against cell division protein FtsZ. Six monoclonal antibodies were
      obtained, and they reacted with FtsZ from cytoplasm and membrane fractions. The
      epitopes in FtsZ were localized by studying the reactions of the monoclonal
      antibodies with fusion proteins truncated at the carboxy terminus and with
      fragments that were obtained by CNBr cleavage of purified FtsZ. Five different
      epitopes were defined. Epitopes I and III reacted with the same monoclonal
      antibody, without showing apparent amino acid homology. Epitope II was defined by
      monoclonal antibodies that cross-reacted with an unknown cytoplasmic 50-kDa
      protein not related to FtsZ. Epitopes IV and V were recognized by different
      monoclonal antibodies. All monoclonal antibodies reacted strongly under native
      conditions, so it is likely that the five epitopes are situated on the surface of
      native FtsZ. By using these data and computer analysis, a provisional model of
      FtsZ is proposed. The FtsZ protein is considered to be globular, with a
      hydrophobic pocket containing GTP-binding elements. Epitopes I and II are
      situated on each side of the hydrophobic pocket. Because the carboxy terminus
      contains epitope V, the carboxy terminus of FtsZ is likely oriented toward the
      protein's surface.

PMID- 7511581
TI  - Lipopolysaccharide epitope expression of Rhizobium bacteroids as revealed by in
      situ immunolabelling of pea root nodule sections.
AB  - To investigate the in situ expression of lipopolysaccharide (LPS) epitopes on
      nodule bacteria of Rhizobium leguminosarum, monoclonal antibodies recognizing LPS
      macromolecules were used for immunocytochemical staining of pea nodule tissue.
      Many LPS epitopes were constitutively expressed, and the corresponding antibodies
      reacted in nodule sections with bacteria at all stages of tissue infection and
      cell invasion. Some antibodies, however, recognized epitopes that were only
      expressed in particular regions of the nodule. Two general patterns of regulated
      LPS epitope expression could be distinguished on longitudinal sections of
      nodules. A radial pattern probably reflected the local physiological conditions
      experienced by endosymbiotic bacteria as a result of oxygen diffusion into the
      nodule tissue. The other pattern of expression, which followed a linear axis of
      symmetry along a longitudinal section of the pea nodule, was apparently
      associated with the differentiation of nodule bacteria and the development of the
      nitrogen-fixing capacity in bacteroids. Basically similar patterns of LPS epitope
      expression were observed for pea nodules harboring either of two immunologically
      distinct strains of R. leguminosarum bv. viciae, although these epitopes were
      recognized by different sets of strain-specific monoclonal antibodies.
      Furthermore, LPS epitope expression of rhizobia in pea nodules was compared with
      that of equivalent strains in nodules of French bean (Phaseolus vulgaris). From
      these observations, it is suggested that structural modifications of Rhizobium
      LPS may play an important role in the adaptation of endosymbiotic rhizobia to the
      surrounding microenvironment.

PMID- 7511582
TI  - Alp suppression of Lon: dependence on the slpA gene.
AB  - We have previously found that plasmids carrying the Escherichia coli alp gene
      (now to be called alpA) suppress two phenotypes of a delta lon protease mutant,
      overproduction of capsular polysaccharide and sensitivity to UV light.
      Suppression of these lon phenotypes is most likely explained by the increased
      degradation of the Lon substrates responsible for these phenotypes. We have
      called this suppressing protease activity Alp protease. The Alp protease activity
      is detected in cells after introduction of plasmids carrying the alpA gene, which
      encodes an open reading frame of 70 amino acids. Insertions which abolish Alp
      activity interrupt this open reading frame. We have used Tn10 and lambda placMu
      mutagenesis to identify a chromosomal locus, slpA, that is required for alpA+
      suppression of delta lon. This locus maps at 57 min, close to the chromosomal
      location of alpA. The expression of beta-galactosidase from a lac transcriptional
      fusion to slpA is increased six- to eightfold when the alpA+ gene is present on a
      multicopy plasmid. Therefore, AlpA acts as a transcriptional regulator of the
      slpA gene(s); activation of slpA transcription is necessary to suppress the
      phenotypes of a delta lon mutation. In an accompanying paper (J. E. Kirby, J. E.
      Trempy, and S. Gottesman, J. Bacteriol. 176:2068-2081, 1994), we show that
      neither AlpA nor SlpA is a component of the protease itself but that they are
      part of a regulatory cascade which leads to expression of the Alp protease.

PMID- 7511583
TI  - Excision of a P4-like cryptic prophage leads to Alp protease expression in
      Escherichia coli.
AB  - The Escherichia coli K-12 alpA gene product, when overproduced from a multicopy
      plasmid, leads to suppression of the capsule overproduction and UV sensitivity
      phenotypes of cells mutant for the Lon ATP-dependent protease. This suppression
      has previously been shown to correlate with increased in vivo activity of a
      previously unknown energy-dependent proteolytic activity capable of degrading Lon
      substrates, the Alp protease. We show in an accompanying paper that alpA, which
      has homology to a short open reading frame in bacteriophage P4, acts as a
      positive transcriptional regulator of slpA, a gene linked to alpA and necessary
      for suppression of lon mutants (J. E. Trempy, J. E. Kirby, and S. Gottesman, J.
      Bacteriol. 176:2061-2067). The sequence of slpA suggests that it encodes an
      integrase gene closely related to P4 int and that both alpA and slpA are part of
      a cryptic P4-like prophage. AlpA expression increases SlpA synthesis. Increased
      SlpA leads, in turn, to the excision and loss of the cryptic prophage. Excision
      is dependent on integration host factor as well as on SlpA. Prophage excision is
      necessary but not sufficient for full expression of the Alp protease. A second
      function (named AHA) allows full protease expression; this function can be
      provided by the kanamycin resistance element from Tn903 when the element is
      present on a multicopy plasmid. Excision and loss of the cryptic prophage
      apparently allow expression of the Alp protease by inactivating a small stable
      RNA (10Sa RNA) encoded by the ssrA gene. The precursor of this RNA has its 3' end
      within the cryptic prophage; the mature 3' end lies within the prophage attL
      site. Inactivation of ssrA by insertional mutagenesis is sufficient to allow
      expression of the suppressing Alp protease, even in the presence of the cryptic
      prophage. Therefore, 10Sa RNA acts as a negative regulator of protease synthesis
      or activity, and prophage excision must inactivate this inhibitory function of
      the RNA.

PMID- 7511585
TI  - Argininosuccinate synthetase mRNA and activity are induced by immunostimulants in
      vascular smooth muscle. Role in the regeneration or arginine for nitric oxide
      synthesis.
AB  - Nitric oxide synthase produces NO, citrulline, water, and NADP at the expense of
      arginine, NADPH, and dioxygen. While citrulline has been considered to be an
      inert by-product of the high output inducible isoform of NO synthase (iNOS), we
      show here that immunostimulants induce a metabolic pathway in vascular smooth
      muscle cells, which enables them to regenerate arginine from citrulline.
      Regeneration of arginine from citrulline is accomplished by two urea cycle
      enzymes: arginino-succinate synthetase (AS) and argininosuccinate lyase (AL).
      Whereas AL is constitutive to vascular smooth muscle cells, AS mRNA and enzyme
      activity is markedly induced in cells by treatment with bacterial
      lipopolysaccharide (LPS). The induction of AS mRNA and activity by LPS follows a
      time course which mirrors that for iNOS but lags 1-2 h behind. As shown for iNOS,
      interferon-gamma does not itself induce AS but is synergistic with LPS. AS
      induction is suppressed by glucocorticoids, actinomycin D, and, to a lesser
      extent, cycloheximide. On the other hand, AS induction is unaffected by an excess
      of citrulline or the inhibitor of iNOS, N omega-methyl-L-arginine. Our results
      show the urea cycle enzymes AS and AL confer cells with the capacity to produce
      NO without a need for exogenous arginine. In conjunction with NOS, citric acid
      cycle enzymes that covert fumarate to oxaloacetate (fumarase and malate
      dehydrogenase) and oxaloacetate to aspartate (aspartate transaminase), AS and AL
      form a novel arginine-citrulline cycle that enables high output NO production by
      cells.

PMID- 7511586
TI  - The point mutation Arg615-->Cys in the Ca2+ release channel of skeletal
      sarcoplasmic reticulum is responsible for hypersensitivity to caffeine and
      halothane in malignant hyperthermia.
AB  - Malignant hyperthermia (MH) is an autosomal dominant myopathy. Molecular genetic
      studies have shown that the alteration of Arg615 to Cys in the Ca2+ release
      channel of skeletal muscle sarcoplasmic reticulum (ryanodine receptor) is
      cosegregated with porcine MH (Fujii, J., Otsu, K., Zorzato, F., de Leon, S.,
      Khanna, V. K., Weiler, J. E., O'Brien, P. J., and MacLennan, D. H. (1991) Science
      253, 448-451; Otsu, K., Khanna, V. K., Archibald, A., and MacLennan, D. H. (1991)
      Genomics 11, 744-750). Here, using the fluorescence calcium indicator indo-1, we
      determined the concentration of ionized cytosolic calcium in myoblastic cells
      transfected with either the wild-type or mutated ryanodine receptor cDNA. The
      cells expressing the mutant ryanodine receptor showed higher sensitivity to
      caffeine, which induces Ca2+ release from the sarcoplasmic reticulum through the
      ryanodine receptor. Exposure to clinical doses of halothane resulted in a rapid
      increase of [Ca2+]i in cells expressing the mutated ryanodine receptor, whereas
      no [Ca2+] changes were observed in cells expressing the wild-type ryanodine
      receptor. These results provide definite evidence that a single amino acid
      mutation, Arg615-->Cys, in the ryanodine receptor is causative of MH.

PMID- 7511584
TI  - Tinkering with transporters: periplasmic binding protein-dependent maltose
      transport in E. coli.
AB  - Periplasmic binding protein-dependent transport systems represent a common
      mechanism for nutrient and ion uptake in bacteria. As a group, these systems are
      related to one another and to other transporters of both prokaryotes and
      eukaryotes, based on sequence similarity within an ATP-binding subunit and
      overall structural organization. These transporters probably all use energy
      derived from ATP to pump substrates across membranes. Although there is
      considerable information about the sequences and identity of the transporters,
      there is little information about how they work. That is, where do ligands bind?
      Where do the subunits or domains interact with one another? How is the energy of
      nucleotide binding and/or hydrolysis converted to conformational changes? In
      order to address these questions we have taken a genetic approach that involves
      studying mutant forms of a transporter. Rather than study mutations that result
      in complete loss of function, the study of mutations which perturb or alter the
      normal function of the transporter in a defined manner has provided a limited
      insight into how the answers to these questions may be obtained.

PMID- 7511587
TI  - Factor for inversion stimulation-dependent growth rate regulation of individual
      tRNA species in Escherichia coli.
AB  - We have studied the involvement of the factor for inversion stimulation (FIS) in
      the growth rate-dependent expression of the arginine, leucine, and methionine
      acceptor tRNA species. The concentration of individual tRNA species relative to
      16 S rRNA was determined by blot hybridization using RNA preparations from
      bacteria with the fis gene deleted and from isogenic wild type bacteria. The RNA
      preparations were obtained from bacteria growing under steady state conditions in
      different media. The levels of tRNA(1Leu), tRNA(2Arg), tRNA(4Arg), and tRNA(5Arg
      decreased in the fis bacteria, relative to the wild type. The difference in
      levels increased with increasing growth rate. Surprisingly, tRNA(3Leu),
      tRNA(rMet), and tRNA(eMet) showed the opposite response, with an increase of the
      tRNA/16 S ratio in the fis bacteria. The tRNA(2Leu, tRNA(4Leu), tRNA(5Leu), and
      tRNA(3 Arg) had unaffected tRNA/16 S ratios in fis cells. We conclude that FIS,
      directly or indirectly, is involved in growth rate regulation of some tRNA
      species and that it affects the composition of the cellular tRNA pool.

PMID- 7511589
TI  - A tyrosine phosphorylation requirement for cytotoxic T lymphocyte degranulation.
AB  - Phorbol myristate acetate (PMA) plus ionomycin induces the tyrosine
      phosphorylation of several cytotoxic T lymphocyte (CTL) substrates, including one
      with an apparent molecular weight of 100,000 (pp100) in cloned murine CTL. cis
      Unsaturated fatty acids and low concentrations of phenylarsine oxide specifically
      inhibit the tyrosine phosphorylation of pp100. Genistein also inhibits tyrosine
      phosphorylation of pp100, but not with the same specificity as cis-fatty acids or
      low concentrations of phenylarsine oxide. Degranulation triggered by PMA plus
      ionomycin is inhibited by cis-fatty acids, low concentrations of phenylarsine
      oxide, and genistein, under the same conditions that these agents inhibit
      tyrosine phosphorylation of pp100. Depleting CTL of protein kinase C (PKC)
      activity by prolonged exposure to PMA eliminates the increase in tyrosine
      phosphorylation when challenged by PMA plus ionomycin, but not when these PKC
      depleted CTL are activated by cognate target cells, immobilized anti-T cell
      receptor (TCR) antibodies, or concanavalin A. Tyrosine phosphorylation of pp100
      triggered by TCR engagement in PKC-depleted cells is inhibited by cis-fatty acids
      and phenylarsine oxide, indicating that the inhibitory mechanism of the tyrosine
      phosphorylation of pp100 is independent of PKC. Furthermore, because all three
      tyrosine phosphorylation inhibitors are unlikely to inhibit PKC, these results
      suggest that, in addition to PKC activation and a rise in intracellular Ca2+, CTL
      degranulation requires the tyrosine phosphorylation of a CTL substrate(s), in
      addition to phospholipase C, and the present results are consistent with pp100 as
      that substrate. Taken together with previous studies, these results suggest that
      tyrosine phosphorylation of pp100 may play a central role in CTL function.

PMID- 7511588
TI  - Involvement of cytoplasmic calcium and protein kinases in the regulation of
      atrial natriuretic factor secretion by contraction rate and endothelin.
AB  - To characterize the effects of the cellular events associated with contraction on
      atrial natriuretic factor (ANF) secretion, primary neonatal rat atrial myocytes
      were electrically paced to contract while being monitored for ANF release,
      cytoplasmic calcium, phosphoinositide hydrolysis, and protein kinase C
      activation. Similar measurements were also carried out in the presence of
      endothelin-1 (ET) for comparison of contraction-related and hormone-stimulated
      ANF secretion. Pacing (6-8 Hz) immediately increased ANF secretion by 3-5-fold
      and the time-averaged cytoplasmic calcium concentration (as monitored with indo-1
      fluorescence) varied with pace frequency in a similar manner, suggesting that
      cytoplasmic calcium may play a key role in pace-induced ANF secretion.
      Furthermore, nifedipine and ryanodine, which inhibited the contractile calcium
      transients, inhibited pace-induced ANF release, whereas Bay K 8644 increased both
      the calcium transients and ANF secretion. Pace-induced ANF release was also
      completely inhibited by KN-62, a specific inhibitor of Ca2+/calmodulin-dependent
      protein kinase II (CaMK) but was not inhibited by chelerythrine, a protein kinase
      C-selective inhibitor. Pace-induced ANF release averaged 40% of that elicited by
      ET which is known to require both PKC and CaMK for maximal effects on ANF
      secretion. The effects of pacing and ET on ANF secretion were approximately
      additive. In contrast to pacing, ET strongly stimulated phosphoinositide
      hydrolysis, activated PKC, and did not increase cytoplasmic calcium. Thus,
      regulation of ANF secretion by contraction rate depends primarily on the
      contractile calcium transients and CaMK and is independent of PKC.

PMID- 7511590
TI  - Role of gamma 87 Gln in the inhibition of hemoglobin S polymerization by
      hemoglobin F.
AB  - Previous studies suggested that gamma 87 Gln in hemoglobin (Hb) F is an important
      site for promoting inhibition of Hb S (alpha 2 beta 2(6 Glu-->Val) polymerization
      by Hb F. We engineered and isolated the double mutant (Hb alpha 2 beta 2(6 Glu-
      >Val,87 Thr-->Gln) using a yeast expression system and characterized
      polymerization properties of this modified tetramer in an effort to clarify the
      role of Gln at position 87 in inhibiting Hb S polymerization. Electrophoretic
      mobility and absorption spectra of this double mutant were the same as that of Hb
      S, while oxygen affinity was higher, and effects of organic phosphates on oxygen
      affinity were reduced. The deoxy form of the double mutant showed a
      characteristic delay time prior to polymerization in vitro. The critical
      concentration for polymerization of the double mutant was about 1.5 times higher
      than Hb S, and delay and polymerization times were much longer than Hb S at the
      same hemoglobin concentrations. The logarithmic plot of delay time versus
      hemoglobin concentration for the double mutant showed a straight line that was
      intermediate between lines for AS and FS mixtures. These results and those of
      kinetics of polymerization of Hb S/double mutant mixtures indicate that
      substitution of Gln for Thr at beta 87 in Hb S prolongs delay time and inhibits
      polymerization, although the double mutant forms polymers like Hb S.

PMID- 7511591
TI  - Characterization of the substance P receptor-mediated calcium influx in cDNA
      transfected Chinese hamster ovary cells. A possible role of inositol 1,4,5
      trisphosphate in calcium influx.
AB  - In Chinese hamster ovary cells expressing the substance P (SP) receptor clone
      (CHO-SPR cells), we examined SP-stimulated [Ca2+]i changes by microscopic
      fluorescence analysis and electrophysiological recordings. In fura-2-loaded
      cells, SP (1 microM) induced a prolonged elevation of [Ca2+]i, which comprised a
      rapid and transient Ca2+ mobilization and a prolonged phase of Ca2+ entry, but
      thrombin (1 unit/ml) induced only transient elevation of [Ca2+]i. The formation
      of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) was stimulated to 230% above the
      control by SP but 10% by thrombin 10 s after stimulation. In whole cell clamp
      recordings, SP induced a long lasting inward current, whereas thrombin did not
      evoke an inward current. Gq alpha antibody applied intracellularly blocked the SP
      induced current, but GS alpha antibody did not block it. Furthermore,
      decavanadate and heparin, inhibitors of Ins(1,4,5)P3 binding to its receptor,
      suppressed the SP-induced current. In cell-attached patch, bath-applied SP
      activated channel currents carried by Ba2+, Ca2+, or Na+. In inside-out patches,
      Ins(1,4,5)P3, but neither inositol 1,3,4-trisphosphate nor inositol 1,3,4,5
      tetrakisphosphate, activated channel currents carried by Ba2+, Ca2+, or Na+. The
      channel activity induced by Ins(1,4,5)P3 was abolished by heparin. These results
      demonstrate that SP induces Ca2+ entry through activation of cation channels and
      suggest that Ins(1,4,5)P3 may regulate both SP-induced Ca2+ mobilization and Ca2+
      entry in CHO-SPR cells.

PMID- 7511592
TI  - Identification of putative ligand binding sites within I domain of integrin alpha
      2 beta 1 (VLA-2, CD49b/CD29)
AB  - Integrin alpha 2 beta 1 is a cell surface adhesion receptor for collagen and
      echovirus 1. Here we localized the epitopes for anti-alpha 2 monoclonal
      antibodies using interspecies (human/bovine) alpha 2 chimeras with different
      lengths of human alpha 2 sequence on the amino-terminal side and site-directed
      mutagenesis. The antibodies that block the collagen and/or echovirus 1 binding to
      human alpha 2 beta 1 (6F1, RMAC11, 12F1, and AA10) recognizes a small region
      (residues 173-259) within the I domain. Asp-160 and Arg-242 are critical for
      binding of the two other function-inhibiting antibodies, P1H5 and 5E8,
      respectively. Notably, mutations of Asp-151 and Asp-254 block the binding of
      alpha 2 beta 1 to collagen. These data suggest that the I domain (residues 140
      359) is critically involved in the ligand/receptor interactions, and collagen and
      echovirus 1 binding sites are adjacent or overlapping within the I domain. The
      sequence of the residues 173-259 of alpha 2 overlap with the peptide sequences
      (M11 and M20) that derive from von Willebrand factor A1 and A3 domains
      (homologous to the alpha 2 I domain) and block von Willebrand factor/collagen
      interaction, suggesting that the epitope region of alpha 2 (residues 173-259) may
      really be involved in ligand recognition.

PMID- 7511594
TI  - Independent effects of platelet-derived growth factor isoforms on mitogen
      activated protein kinase activation and mitogenesis in human dermal fibroblasts.
AB  - Mitogen-activated protein kinase (MAPK) is activated in many cell types in
      response to growth factors during the G0-G1 transition in the cell cycle. We
      investigated the effects of platelet-derived growth factor (PDGF) AA and PDGF BB
      on activation of MAPK in human dermal fibroblasts, and asked whether its
      activation correlates with proliferative responses of human fibroblasts to PDGF
      AA and PDGF BB. Treatment with either PDGF isoform for 20 min resulted in equal
      phosphorylation of MAPK as visualized by gel shifts in Western blotting with anti
      MAPK polyclonal antibody. This finding was confirmed by measurements of MAPK
      activity in response to increasing doses (2-20 ng/ml) of PDGF AA and PDGF BB in
      in vitro assays with myelin basic protein as a substrate. PDGF AA was slightly
      less potent than PDGF BB, but both growth factors induced similar maximal
      activations. Kinetics of activation were also similar for both isoforms, with
      maximal induction of MAPK at 10-20 min after growth factor addition followed by a
      gradual decline to control levels at 1 h. Activation of MAPK by both PDGF
      isoforms was also confirmed by measuring myelin basis protein phosphorylation in
      MAPK immunoprecipitates. Thus both PDGF AA and PDGF BB are potent activators of
      MAPK in human dermal fibroblasts. In contrast, PDGF BB elicited a strong
      mitogenic response, while PDGF AA had no significant effect on DNA synthesis in
      human dermal fibroblasts. These data indicate that acute activation of MAPK is
      not sufficient to stimulate cells to progress through cell cycle. PDGF AA may
      have other biologic functions or may play a co-stimulatory role in proliferation
      of human dermal fibroblasts.

PMID- 7511593
TI  - Interleukin-4 stimulates cGMP production by IFN-gamma-activated human monocytes.
      Involvement of the nitric oxide synthase pathway.
AB  - Resting human blood monocytes from some donors were found to produce a small
      amount of 3'-5' guanine cyclic monophosphate (cGMP) in response to interleukin 4
      (IL-4). A much higher response was observed when monocytes were preincubated with
      interferon (IFN-gamma), which alone was ineffective. Preincubation of monocytes
      with IL-4 led, in contrast, to their subsequent incapacity to generate cGMP in
      response to IL-4. The accumulation of cGMP induced by IL-4 in IFN-gamma
      preincubated monocytes was dose-dependent and peaked about 15 min after its
      addition. It was inhibited in the presence of NG-mono-methyl-L-arginine (L-NMMA),
      an inhibitor of the nitric oxide synthase pathway. This suppressive effect of L
      NMMA was reverted by an excess of L- but not of D-arginine. Accumulation of cGMP
      was significantly reduced by addition of soluble guanylyl cyclase inhibitors,
      such as LY83583 [correction of LY83853] and methylene blue, but was not impaired
      in the presence of EGTA, suggesting that the pathway involved is calcium
      independent. In addition, IL-4 induced an increased secretion of nitrite by
      monocytes, that was potentiated by IFN-gamma and inhibited by L-NMMA. Taken
      together, these results suggest that the sequential exposure of monocytes to IFN
      gamma and IL-4 elicits the release of NO from L-arginine, which in turn is
      capable to stimulate soluble guanylyl cyclase.

PMID- 7511596
TI  - Histamine enhances interleukin (IL)-1-induced IL-6 gene expression and protein
      synthesis via H2 receptors in peripheral blood mononuclear cells.
AB  - The regulation of interleukin (IL)-6 synthesis by cAMP-increasing agents remains
      an unresolved issue. Since an increase in cAMP levels via activation of histamine
      H2 receptors does not induce IL-1 beta synthesis but enhances self-induction of
      IL-1 (Vannier, E., and Dinarello, C. A. (1993) J. Clin. Invest. 92, 281-287), we
      investigated whether histamine regulates IL-6 synthesis. Human peripheral blood
      mononuclear cells were stimulated with IL-1 alpha in the absence or presence of
      histamine (1 nM to 100 microM). IL-6 was measured using a specific
      radioimmunoassay. Histamine alone did not induce protein synthesis or mRNA
      accumulation for IL-6. Histamine (1-100 microM) enhanced IL-1 alpha-induced
      synthesis of IL-6 (p < 0.001). Cimetidine and ranitidine, H2 receptor antagonists
      structurally unrelated to each other, completely reversed the histamine-mediated
      increase in IL-1 alpha-induced IL-6 synthesis. However, diphenhydramine, an H1
      receptor antagonist, did not reverse this effect. Prostaglandin E2, an activator
      of adenylate cyclase, also enhanced IL-1 alpha-induced synthesis of IL-6.
      Histamine increased and sustained steady-state levels of IL-6 mRNA in IL-1 alpha
      stimulated cells, but reduced IL-6 mRNA half-life (3.5 h versus 1.8 h). Our
      results indicate that cAMP-increasing agents, such as histamine or prostaglandin
      E2, fail to induce IL-6 synthesis but rather enhance IL-1-induced IL-6 synthesis.

PMID- 7511595
TI  - The DNA-dependent ATPase activity associated with the class II basic
      transcription factor BTF2/TFIIH.
AB  - BTF2/TFIIH from human, delta from rat, and factor b from yeast are multisubunit
      basal transcription factors that have been shown to be closely associated with a
      protein kinase capable of phosphorylating the carboxyl-terminal domain of the
      large subunit of RNA polymerase II (Lu, H., Zawel, L., Fischer, L., Egly, J. M.,
      and Reinberg, D. (1992) Nature 358, 641-645; Serizawa, H., Conaway, R. C., and
      Conaway, J. W. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 7476-7480; Feaver, W. J.,
      Gileadi, O., and Kornberg, R. D. (1991) Cell 67, 1223-1230). We report here that
      a DNA-dependent ATPase and the previously characterized helicase (Schaeffer, L.,
      Roy, R., Humbert, S., Moncollin, V., Vermeulen, W., Hoeijmakers, J., Chambon, P.,
      and Egly, J. M. (1993) Science 260, 58-63) are both associated with BTF2 and
      reside with the p89 polypeptide subunit. The DNA requirement, the effect of
      Sarkosyl and staurosporine inhibitors, as well as nucleotide competition
      experiments, clearly distinguished ATPase/helicase from the carboxyl-terminal
      domain kinase. Using recombinant wild type or mutated p89/ERCC3 polypeptides and
      different forms of DNA template, we show the connection between ATPase and the
      helicase.

PMID- 7511598
TI  - Accessibility of the c-Src SH2-domain for binding is increased during mitosis.
AB  - The Src homology 2 (SH2) region is a noncatalytic domain of Src-family tyrosine
      kinases and other proteins which participants in inter- and intramolecular
      interactions of tyrosine-phosphorylated proteins. A synthetic peptide modeled on
      the c-Src carboxyl terminus, which contains phosphotyrosine at position 527,
      binds recombinant SH2 and the SH2-domain of c-Src which lacks phosphotyrosine
      527. Unphosphorylated peptide does not bind detectably. Thus, the phosphorylated
      peptide is a specific probe for investigating SH2 accessibility. Since Src and
      other tyrosine kinases may participate in regulating events in mitosis, we used
      the SH2-binding probe to test the prediction that decreased tyrosine 527
      phosphorylation would lead to increased accessibility of the c-Src SH2-domain
      during mitosis. Probe binding to overexpressed chicken c-Src was enhanced at
      least 6-fold during mitosis, indicating that the c-Src SH2-domain is more
      accessible in this part of the cell cycle. This suggests that there may be
      mitosis-specific interactions of the c-Src SH2-domain with cellular proteins in
      vivo.

PMID- 7511597
TI  - cDNA cloning of a mouse prostacyclin receptor. Multiple signaling pathways and
      expression in thymic medulla.
AB  - A functional cDNA for a mouse prostacyclin receptor was isolated from a mouse
      cDNA library by reverse transcription polymerase chain reaction and hybridization
      screening. The cDNA encodes a polypeptide of 417 amino acid residues with
      putative seven transmembrane domains and an calculated molecular weight of
      44,722. The amino acid sequence is 30-40% identical in the transmembrane domains
      to those of the mouse prostaglandin (PG) E receptor subtypes and thromboxane A2
      receptor. [3H]Iloprost, a specific prostacyclin receptor radioligand,
      specifically bound to the membrane of Chinese hamster ovary cells permanently
      expressing the cDNA with Kd of 4.6 nM. This binding was displaced with unlabeled
      prostanoids in the order of cicaprost > iloprost, both prostacyclin agonists >
      PGE1 > carbacyclin >> PGD2 approximately STA2, a thromboxane A2 agonist
      approximately PGE2 > PGF2 alpha. Iloprost in a concentration-dependent fashion
      increased cAMP level and generated inositol phosphates in these cells, indicating
      that the receptor couples to multiple signal transduction pathways. Northern blot
      analysis revealed that the mRNA is expressed most abundantly in thymus, followed
      by spleen, heart, and lung. In situ hybridization of thymus showed that it is
      expressed exclusively in medulla and not in cortex.

PMID- 7511599
TI  - Localization of an apolipoprotein A-I epitope critical for lipoprotein-mediated
      cholesterol efflux from monocytic cells.
AB  - The inverse correlation between plasma high density lipoprotein (HDL) levels and
      the risk for cardiovascular disease has been attributed in part to the role of
      HDL in facilitating the transport of cholesterol to the liver for catabolism. One
      component of this reverse cholesterol transport is removal of excess cholesterol
      from peripheral cells. An immunochemical approach was employed to evaluate the
      role of human apolipoprotein (apo) A-I in cellular cholesterol efflux and to test
      the hypothesis that discrete structural domains of the molecule mediate this
      function. Two apoA-I-specific monoclonal antibodies (AI-11 and AI-14) inhibited
      in vitro cellular cholesterol efflux from THP-1 monocytic cells to HDL or apoA-I
      proteoliposomes by approximately 50%. Six other antibodies had no effect although
      three of these bound significant proportions of the apoA-I proteoliposomes.
      Antibody AI-11 binds apoA-I amino acid residues 96-111 (Banka, C. L., Bonnet, D.
      J., Black, A. S., Smith, R. S., and Curtiss, L. K. (1991) J. Biol. Chem. 266,
      23886-23892). The AI-14 epitope was localized to residues 74-105. Therefore, the
      two antibodies that inhibited HDL promotion of cellular cholesterol efflux bound
      overlapping but distinct regions of the apoA-I molecule.

PMID- 7511600
TI  - Functional independence of monomeric CHIP28 water channels revealed by expression
      of wild-type mutant heterodimers.
AB  - CHIP28 is a major water transporting protein in erythrocytes and kidney which
      forms tetramers in membranes (Verbavatz, J. M., Brown, D., Sabolic, I., Valenti,
      G., Ausiello, D. A., Van Hoek, A. N., Ma, T., and Verkman, A. S. (1993) J. Cell
      Biol. 123, 605-618). To determine whether CHIP28 monomers function independently,
      chimeric cDNA dimers were constructed which contained wild-type CHIP28 in series
      with either wild-type CHIP28, a non-water transporting CHIP28 mutant (C189W), or
      a functional but mercurial-insensitive CHIP28 mutant (C189S). Transcribed cRNAs
      were injected in Xenopus oocytes and plasma membrane expression was assayed by
      quantitative immunofluorescence. Water channel function was measured by
      osmotically induced swelling. CHIP28 homo- and heterodimers were targeted to the
      oocyte plasma membrane and functioned as water channels. Relative osmotic water
      permeability (Pf) values (normalized for plasma membrane expression of monomeric
      subunits) were: 1.0 (CHIP28 monomer), 0.0 (C189W), 1.07 (C189S), 1.10 (CHIP28
      CHIP28 dimer) and 0.52 (CHIP28-C189W). The increase in oocyte Pf was linearly
      related to plasma membrane expression of wild-type CHIP28 and C189S subunits.
      HgCl2 (0.3 mM) inhibited channel-mediated Pf in oocytes expressing wild-type
      CHIP28 monomers and dimers by 85-90%, but did not inhibit Pf in oocytes
      expressing C189S. HgCl2 inhibited Pf in oocytes expressing CHIP28-C189S dimers by
      44 +/- 7%, consistent with one mercurial-sensitive and one insensitive subunit in
      the heterodimer. These results indicate that despite their assembly in tetramers,
      monomeric CHIP28 subunits function independently as water channels.

PMID- 7511601
TI  - On the relationship between the mitochondrial inner membrane anion channel and
      the adenine nucleotide translocase.
AB  - The mitochondrial inner membrane anion channel (IMAC) is a transport pathway
      which is believed to be involved in mitochondrial volume homeostasis. The
      protein, however, has not been identified. In this paper, we examine the
      relationship between IMAC and the adenine nucleotide translocator. Many
      inhibitors of the adenine nucleotide translocase are shown to block IMAC,
      including Cibacron blue 3GA, bromcresol green, alizarin red S, agaric acid,
      palmitoyl-CoA, and the fluorescein derivatives erythrosin B, erythrosin
      isothiocyanate, rose bengal, and eosin Y. The following evidence suggests that
      Cibacron blue, agaric acid, and palmitoyl-CoA inhibit by binding to a common
      site. 1) They all only partially block the transport of small anions such as Cl-,
      NO3-, and HCO3-, but completely block the transport of larger anions such as
      malonate. 2) They decrease the IC50 values of each other in a manner consistent
      with competitive binding. 3) N-Ethylmaleimide decreases their IC50 values by a
      similar extent. 4) Inhibition by all shows no dependence on matrix pH and only a
      small dependence on medium pH. It is suggested that these agents may selectively
      bind to an open state of IMAC and inhibit by decreasing its conductance. The
      physiological nucleotides CoA, NAD+, NADH, NADP+, NADH, and ATP do not inhibit;
      in fact, IMAC is shown to transport ATP. Despite these similarities between IMAC
      and the adenine nucleotide translocase, IMAC appears to be a separate entity,
      since some of the IC50 values differ by up to 8-fold, and carboxyatracyloside,
      the most selective inhibitor of the adenine nucleotide translocase, has no effect
      on IMAC. In addition, IMAC is also able to transport AMP, while the adenine
      nucleotide translocase does not.

PMID- 7511602
TI  - Structural coincidence of alpha PDGFR epitopes binding to platelet-derived growth
      factor-AA and a potent neutralizing monoclonal antibody.
AB  - We have generated two groups of deletion mutants of the alpha PDGFR and one group
      of chimeras between alpha PDGFR and beta PDGFR to further investigate the
      structural requirements of the alpha PDGFR for binding to platelet-derived growth
      factor (PDGF)-AA and to a monoclonal antibody against alpha PDGFR (designated as
      mAb-alpha R1). The mAb-alpha R1 has recently been reported to block high affinity
      binding of PDGF-AA to alpha PDGFR. The first group of mutants were carboxyl
      terminal deletion mutants encoding the first two immunoglobulin (Ig)-like domains
      (alpha R1-216), the first four Ig-like domains (alpha R1-415), or all five Ig
      like domains (alpha R1-530) of the alpha PDGFR. Since these mutants lacked
      transmembrane domains, their expression in NIH/3T3 cells resulted in secretion of
      the truncated alpha PDGFRs. Using conditioned medium from NIH/3T3 transfectants,
      we showed that mAb-alpha R1 was able to immunoprecipitate each of these secreted
      form of alpha PDGFRs, suggesting that the epitope recognized by mAb-alpha R1 is
      located within Ig-like domains 1 and 2 of the alpha PDGFR. Furthermore, PDGF-AA
      exhibited detectable binding to alpha R1-415 or alpha R1-530 but failed to
      interact with alpha R1-216, suggesting that the first two Ig-like domains of the
      alpha PDGFR are not sufficient for PDGF-AA binding. The second group of alpha
      PDGFR mutants were internal deletion mutants lacking Ig-like loop 1 (alpha R
      delta 49-100), Ig-like loop 2 (alpha R delta 150-189), Ig-like loop 3 (alpha R
      delta 235-290), or part of Ig-like loops 4 and 5 (alpha R delta 375-450). The
      internal deletion mutants were transfected into 32D cells which lack both alpha
      PDGFR and beta PDGFR. PDGF-AA bound with high affinity to 32D cells expressing
      alpha R delta 375-450 but not to 32D cells expressing the other three internal
      deletion mutants, suggesting that the region required for PDGF-AA binding should
      be within the first three Ig-like domains of the alpha PDGFR. In addition, mAb
      alpha R1 bound to 32D cells expressing alpha R delta 235-290 but failed to bind
      32D cells transfected with alpha R delta 49-100 or alpha R delta 150
      189.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7511603
TI  - rse, a novel receptor-type tyrosine kinase with homology to Axl/Ufo, is expressed
      at high levels in the brain.
AB  - We have isolated cDNA clones that encode the human and murine forms of a novel
      receptor-type tyrosine kinase termed Rse. Sequence analysis indicates that human
      Rse contains 890 amino acids, with an extracellular region composed of two
      immunoglobulin-like domains followed by two fibronectin type III domains. Murine
      Rse contains 880 amino acids and shares 90% amino acid identity with its human
      counterpart. Rse is structurally similar to the receptor-type tyrosine kinase
      Axl/Ufo, and the two proteins have 35 and 63% sequence identity in their
      extracellular and intracellular domains, respectively. To study the synthesis and
      activation of this putative receptor-type tyrosine kinase, we constructed a
      version of Rse (termed gD-Rse, where gD represents glycoprotein D) that contains
      an NH2-terminal epitope tag. NIH3T3 cells were engineered to express gD-Rse,
      which could be detected at the cell surface by fluorescence-activated cell
      sorting. Moreover, gD-Rse was rapidly phosphorylated on tyrosine residues upon
      incubation of the cells with an antibody directed against the epitope tag,
      suggesting that rse encodes an active tyrosine kinase. In the human tissues we
      examined, the highest level of expression of rse mRNA was observed in the brain;
      rse mRNA was also detected in the premegakaryocytopoietic cell lines CMK11-5 and
      Dami. The gene for rse was localized to human chromosome 15.

PMID- 7511604
TI  - Regulation of keratinocyte growth factor gene expression by interleukin 1.
AB  - Keratinocyte growth factor (KGF) is a stromally derived member of the fibroblast
      growth factor family (FGF7) with potent mitogenic activity on a variety of
      epithelial cells. To identify molecules that regulate the expression of this
      paracrine mediator of epithelial proliferation, we investigated the effects of
      various cytokines and growth factors on KGF production by fibroblasts. The
      proinflammatory cytokine interleukin 1 (IL1) strongly induced the expression of
      KGF RNA in fibroblasts from multiple sources. Platelet-derived growth factor BB,
      IL6, and transforming growth factor alpha caused a moderate elevation, while
      tumor necrosis factor alpha and basic FGF did not alter the level of KGF RNA
      expression. The induction by IL1 of KGF transcript levels was time and dose
      dependent and specifically blocked by anti-IL1 antibodies. Nuclear run on
      experiments indicated that IL1 stimulated KGF gene transcription. Western blot
      analysis and keratinocyte proliferation assays demonstrated a corresponding
      increase in mitogenically active KGF protein in conditioned medium obtained from
      IL1-treated fibroblasts. The stimulation of KGF expression by IL1 and other
      cytokines such as IL6, transforming growth factor alpha, and platelet-derived
      growth factor may provide a mechanism for KGF induction during inflammation that
      would support its proposed role as mediator of reepithelialization and wound
      healing.

PMID- 7511605
TI  - The cytoplasmic domain of myelin glycoprotein P0 interacts with negatively
      charged phospholipid bilayers.
AB  - The intracellular COOH-terminal domain of the glycoprotein, P0, has been proposed
      to be involved in the formation of the major dense line of peripheral myelin. We
      have addressed this hypothesis by generating and subsequently isolating a peptide
      fragment that contains 65 of the 69 residues of the cytoplasmic region of rat P0.
      This peptide, termed P0(intra), bound to artificial phospholipid vesicles and
      caused their rapid aggregation. The peptide-induced aggregation of membrane
      bilayers appeared to result from ionic interactions, since P0(intra) vesicle
      association was decreased by 1) reducing the phosphatidylserine content of the
      membranes, 2) increasing the NaCl concentration of the surrounding buffer, or 3)
      elevating the divalent cation concentration within the buffers. Cationic disc gel
      electrophoresis of P0(intra) revealed at least four charge isoforms of the
      peptide. Treatment of sciatic nerve slices with phorbol ester prior to isolation
      of P0(intra) increased the amount of the more negatively charged species,
      suggesting that at least some of the charge heterogeneity of the peptide can be
      attributed to differing phosphorylation states. The ability of P0(intra) to bind
      to phospholipid bilayers implies that the cytoplasmic domain of P0 may be
      responsible for the formation and maintenance of the myelin major dense line.

PMID- 7511607
TI  - Effects of nucleotide sequence on the specificity of rne-dependent and RNase E
      mediated cleavages of RNA I encoded by the pBR322 plasmid.
AB  - RNase E, an endoribonuclease encoded by the Escherichia coli ams/rne/hmp1 locus,
      cleaves RNA I, an antisense regulator of the replication of ColE1 type plasmids,
      in a single-stranded region near its 5' end. The rne-3071 mutation prolongs the
      RNA 1 half-life in cells cultured at an elevated temperature and imparts
      temperature sensitivity on RNase E isolated from the mutant strain. Here we
      report the effects of specific sequence changes introduced by site-directed
      mutagenesis on the location of ribonucleolytic cleavage near the 5' end of pBR322
      RNA I in rne-3071 and congenic rne+ E. coli and on cleavage of RNA I by RNase E
      in vitro. Primer extension analyses showed that the occurrence and position of
      cleavages in vivo and in vitro are altered highly specifically by sequence
      changes but that the site of cleavage bears no simple relationship to a
      particular nucleotide order. Our results do not support either the notion that
      cleavage by RNase E is determined by a consensus sequence or the contrary view
      that RNase E is a virtually nonspecific single-stranded endonuclease with a
      preference for cutting 5' to an AU dinucleotide.

PMID- 7511606
TI  - A+U content rather than a particular nucleotide order determines the specificity
      of RNase E cleavage.
AB  - Ribonuclease E has a central role in Escherichia coli mRNA decay and is dependent
      on a functional product of the rne (also called ams or hmp1) gene. We
      investigated the requirements for RNase E cleavage by introducing random
      mutations into the decanucleotide region at the 5' end of pACYC184 RNA I and
      studying the effects of these mutations on the position of rne-dependent cleavage
      in vivo and RNase E-mediated cutting in vitro. We find that the precise point of
      RNase E cleavage can be altered specifically and reproducibly by sequence changes
      in the region cleaved and, therefore, is not determined by a distance measured in
      nucleotides from any other sequence or region of secondary structure in RNA I.
      Although cleavage by RNase E occurs within sequences rich in A and/or U
      nucleotides and is affected by the extent of continuity of A and U nucleotides in
      the regions cleaved, there is no simple relationship between the order of
      nucleotides and the phosphodiester bond cleaved. Thus, our results are not
      consistent with either the notion that RNase E cleavages are determined by a
      simple consensus sequence or the contrary view that RNase E has few primary
      structural constraints other than a preference for cleaving 5' to an AU
      dinucleotide.

PMID- 7511608
TI  - Retention and degradation of proteins containing an uncleaved
      glycosylphosphatidylinositol signal.
AB  - Glycosylphosphatidylinositol (GPI) membrane anchor attachment is directed by a
      COOH-terminal signal that is proteolytically removed and replaced with a
      preformed GPI anchor in a coupled reaction. Failure to complete proteolytic
      cleavage and anchor addition results in the retention of an uncleaved precursor
      in a post-endoplasmic reticulum (ER) compartment. In this report, we address
      three issues: (i) the exact position of the transport block, (ii) the subsequent
      fate of the retained molecules, i.e. where are they degraded, and (iii) the
      mechanism whereby these proteins are selected for retention. Using decay
      accelerating factor (DAF), we provide evidence that failure to cleave the GPI
      signal totally prevents O-glycosylation, suggesting that the uncleaved
      polypeptides are not transported into the cis-Golgi complex. This implies that
      transport is blocked at the boundary between the ER-Golgi intermediate
      compartment and the Golgi stacks. The degradation of an intracellularly retained
      human growth hormone (hGH)-DAF fusion protein containing a nonfunctional GPI
      signal shows some features of ER degradation, i.e. the degradation is insensitive
      to leupeptin, chloroquine, and ammonium chloride, and is inhibited at 16 degrees
      C or after ATP depletion. However, morphological evidence points to a pathway
      resembling autophagy. To reconcile these observations, we suggest either that
      hGHDAF is degraded by two distinct pathways (ER degradation and autophagy) or
      that ER degradation takes place in an ER-associated vesicular compartment in a
      process resembling autophagy. Using as probes a soluble hGH receptor and an
      antibody recognizing only native hGH, we show that a significant fraction of the
      retained protein is correctly folded, ruling out general misfolding as the basis
      for retention. We also show that hGHDAF fusion proteins are present in high
      molecular weight, disulfide-linked aggregates in COS cells. We suggest a model
      for retention in which the uncleaved GPI signal drives the formation of large
      micelle-like aggregates that cannot be secreted.

PMID- 7511609
TI  - Identification of a novel integrin binding site in fibronectin. Differential
      utilization by beta 3 integrins.
AB  - Fibronectin (Fn) binding to the integrins alpha IIb beta 3 and alpha v beta 3
      involves the Arg-Gly-Asp sequence. The identification of other regions of Fn that
      interact with alpha IIb beta 3 suggests a potential mechanism for differential
      ligand recognition by integrins. We report here the identification of an 11
      residue peptide sequence from the 9th type III repeat of Fn (3Fn9), which
      inhibits ligand binding to alpha IIb beta 3 by interacting directly with this
      receptor. Mutational analysis demonstrated that this same region was involved in
      the formation of epitopes for two anti-Fn mAbs that inhibit Fn binding to alpha
      IIb beta 3, thus emphasizing the role of this site in the macromolecule.
      Molecular modeling of the 3Fn9-10 modules suggested that Fn residues Asp1373
      Thr1383 are at least 25 A distant from the Arg-Gly-Asp site and therefore does
      not directly interact with it. The 3Fn9 site was differentially recognized by the
      beta 3 integrin family. The Asp1373-Thr1383 peptide failed to inhibit ligand
      binding to alpha v beta 3, a recombinant Fn Ala1235-Ser1436 fragment was not
      recognized by alpha v beta 3, and addition of the 3Fn9 module to the amino
      terminus of the 3Fn10 did not affect the potency of inhibition of Fn binding to
      alpha v beta 3. Thus, a novel integrin recognition site in the 3Fn9 module of Fn
      that is differentially recognized by the beta 3 integrins has been localized
      within the residues Asp1373-Thr1383.

PMID- 7511611
TI  - Characterization of the chromosomal gene and promoter for human insulin-like
      growth factor binding protein-5.
AB  - To better understand the regulation of insulin-like growth factor binding protein
      5 (IGFBP-5) expression, we cloned the IGFBP-5 gene from human genomic libraries
      and identified a region in the 5' flanking sequence which functions as a
      promoter. The human IGFBP-5 gene is divided into four exons which, primarily due
      to a first intron of approximately 25 kilobases, span approximately 33 kilobases
      of DNA. Southern analysis identified a single copy of the IGFBP-5 gene in the
      haploid human genome, and several independent mapping strategies found this gene
      tightly linked with, and in opposite transcriptional orientation to, the IGFBP-2
      gene at chromosomal region 2q33-34. Primer extension studies identified the IGFBP
      5 mRNA cap site 772 base pairs (bp) 5' to the first nucleotide of the translation
      start codon. Analysis of the 5'-flanking sequence identified a potential TATA
      element beginning 33 bp 5' to the mRNA cap site. When a DNA fragment containing
      this cap site and 461 bp of upstream sequence was placed 5' to the
      chloramphenicol acetyltransferase reporter gene and transfected into MDA-MB-468
      human breast cancer cells, it directed chloramphenicol acetyltransferase
      expression in an orientation-specific manner, suggesting that this region
      contains elements essential for IGFBP-5 promoter activity.

PMID- 7511612
TI  - On the role of the bithiazole moiety in sequence-selective DNA cleavage by
      Fe.bleomycin.
AB  - A recent study of Fe(II).bleomycin-mediated DNA strand scission suggested that
      the metal binding domain of the drug is also the primary determinant of the
      observed sequence selectivity of strand scission (Carter, B. J., Murty, V. S.,
      Reddy, K. S., Wang, S.-N., and Hecht, S. M. (1990) J. Biol. Chem. 265, 4193
      4196). Although it is well established that the bithiazole moiety+C-terminal
      substituent of bleomycin are required for DNA binding, the role of the bithiazole
      in sequence-selective DNA recognition remains unclear. To determine whether the
      bithiazole moiety exhibits an intrinsic DNA binding selectivity, three synthetic
      EDTA-conjugated bithiazole derivatives were used to mediate DNA cleavage in the
      presence of Fe2+ and dithiothreitol. Incubation of these Fe(II).EDTA-bithiazoles
      in the presence of a 5'-32P end-labeled DNA duplex resulted in strand scission at
      every position to essentially the same extent. The relative cleavage efficiencies
      among the bithiazoles were a strong function of their ionic state. These findings
      imply that the bithiazoles can bind to many sites on the DNA; they support a
      model of bleomycin-DNA interaction in which the bithiazole moiety+C-terminal
      substituent are required only for DNA binding, whereas the metal binding domain
      is responsible for metal ion coordination and oxygen activation as well as being
      the primary determinant of sequence-selective DNA cleavage.

PMID- 7511613
TI  - RNA/protein interactions in the 5'-untranslated leader of HSP70 mRNA in
      Drosophila lysates. Lack of evidence for specific protein binding.
AB  - We have investigated the hypothesis that preferential translation of the heat
      stress mRNAs requires the binding of a trans-acting protein factor. 32P-Labeled
      RNA probes covering the 5'-untranslated region (5'-UTR) of HSP70 mRNA were
      synthesized, and gel retardation and UV cross-linking assays performed to
      identify trans-acting sequence-specific RNA-binding factors. The results indicate
      that no HSP70 5'-UTR RNA-specific binding proteins exist. Reducing the
      "stringency" in the gel retardation binding analyses revealed several non
      sequence-specific RNA-binding complexes. The proteins bind RNA more strongly than
      DNA, show minor preferences for specific sequences, but none binds more strongly
      to the HSP70 5'-UTR than to other non-heat stress RNAs. Ultraviolet cross-linking
      analysis identifies two principal HSP70 5'-UTR binding proteins, of approximately
      50 and 70 kDa. The p50 binding activity is increased severalfold for all mRNAs in
      heat-stressed lysates, and its binding produces the primary gel-retarded complex.
      Further detailed analyses were performed to probe for any possible heat
      influenced changes. RNA/protein interactions are not affected by capping. Neither
      the kinetics nor the salt sensitivity of protein binding is affected by heat.
      Binding analyses using partial or complete HSP70 5'-UTR give qualitatively
      similar conclusions. Binding analyses were also carried out with several "normal"
      5'-UTRs to investigate whether a heat-induced repressor might be activated by
      heating. No normal mRNA-specific heat-induced binding changes are detected. We
      conclude that heat-induced alterations in RNA-binding proteins do not mediate
      preferential translation of heat stress mRNAs or repression of normal mRNAs.

PMID- 7511614
TI  - Epidermal differentiation and keratin gene expression.
AB  - The epidermis of the skin is a stratified squamous epithelium, which plays an
      important protective role. It manifests this role by building an extensive
      cytoskeletal architecture, the unique feature of which is the presence of keratin
      filaments. There are two major pairs of keratins in the epidermis: one pair is
      expressed in dividing cells and the other expressed in terminally differentiating
      cells. As such, keratins provide useful biochemical markers to explore the
      molecular mechanisms underlying the balance between growth and differentiation in
      the epidermis. Here, I review what is currently known about epidermal growth and
      differentiation, and how an understanding of keratin gene expression has been
      useful in elucidating regulatory pathways in the skin.

PMID- 7511610
TI  - Identification and cellular localization of unique interferon mRNA from human
      placenta.
AB  - Although constitutive expression of trophoblast or pregnancy-associated
      interferon (IFN) has long been recognized, their cDNA sequences have been
      determined for only ruminant ungulates. Here we show a human trophoblast IFN
      (htIFN) cDNA whose nucleotide sequence is very similar (85% identity) to that of
      ovine and bovine trophoblast IFNs, IFN tau s. Like ruminant IFN tau s, htIFN
      cDNAs contain an open reading frame of 195 codons including a signal sequence of
      23 amino acids, resulting in a mature polypeptide of 172 amino acids. The deduced
      amino acid sequence of htIFN shares 73, 62, and 56% identities with ovine IFN
      tau, human IFN alpha II, and human IFN alpha I, respectively. However, the
      expression of htIFN is not limited to a specific period of pregnancy because
      transcripts of htIFN genes are detected in human lymphocytes, cells obtained by
      amniocentesis (amniocytes), first trimester, and term placentas. Human
      trophoblast IFN mRNA is localized mainly in extravillous trophoblasts cells of
      placental villi, particularly in the migrating cytotrophoblasts cells, which
      eventually replace maternal endothelial cells in spiral arteries of the decidua.
      Both sense and antisense mRNAs for human IFN alpha II are localized in the outer
      layer of villous structures. Coexistence of these mRNAs at the placental villi
      throughout pregnancy suggests that, in addition to a role in placental cell
      growth and differentiation, IFNs may play a role protecting the fetus in viral
      environments.

PMID- 7511616
TI  - Dysfunction of CFTR bearing the delta F508 mutation.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is mutated in
      patients with cystic fibrosis (CF). The most common CF-associated mutation is
      deletion of phenylalanine at residue 508, CFTR delta F508. When expressed in
      heterologous cells, CFTR bearing the delta F508 mutation fails to progress
      through the normal biosynthetic pathway and fails to traffic to the plasma
      membrane. As a result, CFTR delta F508 is mislocalized and is not present in the
      apical membrane of primary cultures of airway epithelia. Consequently, the apical
      membrane of CF airway epithelia is Cl- -impermeable, a defect that probably
      contributes to the pathogenesis of the disease.

PMID- 7511615
TI  - Defective acidification of the biosynthetic pathway in cystic fibrosis.
AB  - Cystic fibrosis is associated with defective epithelial sodium chloride and fluid
      secretion in epithelia. In addition, there is widespread reductions in
      sialylation of secreted proteins and increases in the sulfation and fucosylation
      of mucus glycoproteins. The major morbidity in the disease is due to the
      colonization of respiratory epithelia by Pseudomonas. The cystic fibrosis gene
      (CFTR) is a cyclic AMP activated Cl channel, which when mutated is retained in
      the endoplasmic reticulum. We postulate that this Cl channel is responsible for
      effective acidification of the Golgi. In CF cells, we demonstrate the Golgi pH is
      higher than in normal cells and suggest that the abnormalities in glycoprotein
      biosynthesis is due to changes in the kinetics of sialyl transferase, a pH
      sensitive enzyme. Defects in sialylation also result in decreased sialylation of
      glycolipids and asialogangliosides are potential Pseudomonas receptors.

PMID- 7511617
TI  - Phenotypic conversions in renal development.
AB  - The transporting epithelia of the kidney are derived from an embryonic rudiment
      containing two distinct cell populations: ureteric bud epithelia and mesenchymal
      cells of the metanephric blastema. The ureteric bud is a caudal outgrowth of the
      Wolffian Duct and gives rise to the renal collecting system by branching
      morphogenesis. The metanephric blastema gives rise to diverse cells of the
      nephron after receiving an inductive stimulus. It has been proposed that
      mesenchymal progenitors of the metanephric blastema derive directly from
      intermediate mesoderm, although this hypothesis has never been tested directly.
      Utilizing direct lineage analysis techniques we demonstrate, in an organ culture
      system, that mesenchymal nephron progenitors are immediate descendants of
      ureteric bud epithelia. Ureteric bud epithelia can give rise to mesenchymal
      nephron progenitors that populate the metanephric blastema by undergoing an
      epithelial-to-mesenchymal transition followed by delamination. If this process
      occurs in vivo, renal morphogenesis can be characterized by two phenotypic
      conversions: an epithelial-to-mesenchymal transition leading to the generation of
      mesenchymal-nephron progenitors, followed by a mesenchymal-to-epithelial
      transition leading to the generation of diverse nephron epithelial cell types. We
      have immortalized an embryonic renal mesenchymal cell line and demonstrate that
      the clonal cell line, RSTEM-1, undergoes phenotypic conversions in vitro,
      providing a suitable model to study the regulation of the epithelial phenotype.

PMID- 7511618
TI  - The cytoskeleton in development of epithelial cell polarity.
AB  - The polarization of intestinal epithelial cells and the stereotypic arrangement
      of their actin-based cytoskeleton have made these epithelia an excellent system
      to explore the organization and formation of a cortical actin-based cytoskeleton.
      Through a combined morphological and biochemical analysis, the molecular
      arrangement of many of the components of the brush border has been elucidated.
      Study of brush border assembly in the Crypts of Lieberkuhn suggests that
      cytoskeletal mRNA and protein expression, as well as morphological development,
      occur rapidly following cell differentiation. Protein kinases appear to be
      important regulators of intestinal cell growth, for differentiating cells in the
      crypts possess 15-fold higher levels of tyrosine phosphorylated proteins than
      differentiated cells of the villus. One of these kinases, pp60c-src, has a 4- to
      7-fold higher activity in crypts and increased association with the cytoskeleton
      than it has in villus cells. The development and maintenance of polarization in
      epithelial cells require the targeting and transport of specific proteins to the
      apical and basolateral plasma membrane. It has been proposed that a dynein-like,
      microtubule-based motor is involved in the transport of apically directed
      materials from the trans-Golgi to the apical plasma membrane. However,
      microtubules do not reach the plasma membrane, but terminate below the actin-rich
      network of filaments comprising the terminal web. We propose that vesicles
      translocate from the Golgi to the apical cytoplasm along microtubules using
      dynein, and then move through the terminal web to reach the apical plasma
      membrane using the actin-based motor myosin-I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511619
TI  - Biogenesis of synaptic vesicles.
AB  - The basic endosomal recycling pathway can be modified to generate transcytotic
      vesicles, storage vesicles and synaptic vesicles. Sorting into synaptic vesicles
      requires specialized sorting information not present in the transcytotic and
      storage vesicle proteins. Using mutagenesis we have distinguished the signals for
      rapid endocytosis and SV targeting in synaptobrevin. Finally, we have evidence
      that synaptic vesicles can be generated from an endosomal compartment in vitro.

PMID- 7511620
TI  - Diagnosis and management of antiphospholipid syndrome.

PMID- 7511621
TI  - Antibodies reactive with an intracellular epitope of a recombinant 64 kDa thyroid
      and eye muscle protein in patients with thyroid autoimmunity and ophthalmopathy.
AB  - We have developed an enzyme-linked immunosorbent assay (ELISA) for the
      measurement of antibodies reactive with a 98 amino acid fragment, called D1, of a
      recombinant thyroid and eye muscle membrane protein corresponding to a MW of 64
      kDa (called 1D) in the serum of patients with thyroid autoimmunity with and
      without ophthalmopathy. Antibodies against the D1 fragment expressed as a fusion
      protein with beta galactosidase, were detected in 29% of patients with thyroid
      associated ophthalmopathy (TAO) of < 1 yr duration, in 33% of those with disease
      of > 3 yr duration, in 40% of patients with Graves' hyperthyroidism (GH) without
      evident eye disease, in 31% of patients with lid lag and retraction but no other
      signs of progressive ophthalmopathy, in 25% of patients with euthyroid Graves'
      disease and in 43% of patients with untreated Hashimoto's thyroiditis (HT), but
      in none of 14 patients with other (non-immunological) thyroid disorders. Although
      tests were positive in 6 out of the 15 patients with ophthalmopathy and no overt
      thyroid autoimmunity overall there was no close association of the antibodies
      with clinical features of the eye disease or its course. In those sera in which
      Western blotting for antibodies reactive with a 64 kDa eye muscle membrane
      protein and ELISA were both carried out there was no close correlation between
      the two tests.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511622
TI  - Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and
      beta subunits, in relation to maternal thyroid stimulation during normal
      pregnancy.
AB  - The main objective of the present study was to present additional evidence of the
      potentially important thyrotropic role of hCG to regulate the maternal thyroid
      gland during normal pregnancy. Sequential determinations (first and last
      trimesters) of intact hCG, free alpha and beta-hCG subunits concentrations (using
      monoclonal IRMAs), and assessment of parameters of thyroid function and thyroid
      volume were carried out in 62 pregnant women who exhibited during the first
      trimester of gestation low TSH levels (< or = 0.20 mU/L), and compared to 276
      pregnant women with normal TSH levels. The prevalence of having low serum TSH
      represented 18% of all pregnancies, with almost one half of cases who transiently
      had undetectable TSH levels. Lowering of TSH was associated with high hCG levels,
      and occurred primarily during the first trimester. About 10% of women with low
      TSH presented transient gestational thyrotoxicosis, frequently associated with
      vomiting. In comparison to control subjects, women with a suppressed serum TSH
      had significantly and markedly higher intact hCG and free beta-hCG subunit
      concentrations. The results suggest that TSH reduction may result from a relative
      oversecretion of both intact hCG and free beta-hCG subunits, compatible with
      three hypotheses: a) transient overexpression of the beta-hCG gene, leading to
      enhanced production of hCG heterodimer; b) increased glycosylation of circulating
      hCG, with in turn a prolonged half life; c) larger syncytiotrophoblast mass with
      increased hCG production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511623
TI  - Costimulation of T lymphocytes with integrin ligands intercellular adhesion
      molecule-1 or vascular cell adhesion molecule-1 induces functional expression of
      CTLA-4, a second receptor for B7.
AB  - Costimulation by the CD28 ligand B7/BB1 plays an important role during T cell
      proliferation primarily by augmenting synthesis of IL-2 and other cytokines.
      Resting CD4+ T cells express CD28 but not CTLA-4 on their surface. Costimulation
      of T cells with ICAM-1 or VCAM-1 induced CTLA-4 expression and up-regulated CD28
      expression. CD28 and CTLA-4 were independently distributed on the surface of
      activated T lymphoblasts. When co-immobilized with anti-TCR mAb both anti-CD28
      and anti-CTLA-4 mAb augmented T cell proliferation. Although anti-CD28-mediated
      augmentation of T cell proliferation was stronger than that seen with anti-CTLA-4
      mAb, together these two mAb caused supraadditive augmentation of T cell
      proliferation. The augmentation of the effects of anti-CD28 mAb by anti-CTLA-4
      mAb was greater at low occupancy of CD28 by anti-CD28 mAb. Costimulation of CD28+
      CTLA-4+ T cells with anti-CTLA-4 caused three- to fivefold increase in IL-2
      production, whereas similar treatment with anti-CD28 caused > 40-fold increase.
      The costimulatory effect of B7 on primed T cells was partially inhibited by Fab
      anti-CD28 mAb. Anti-CTLA-4 mAb alone did not inhibit B7-induced response but
      caused modest increase in the inhibitory effect of anti-CD28 Fab. On integrin
      mediated costimulation, Ag-specific CD4+ T cell lines also up-regulated their
      CTLA-4 expression, and proliferation of these cells was augmented by anti-CTLA-4
      mAb. Unlike that of CD28, ligation of CTLA-4 alone failed to mobilize
      intracellular [Ca2+]. However, coligation of CTLA-4 and TCR induced stronger
      [Ca2+] response in Ag-specific T cell lines than that seen with TCR alone. These
      results suggest that integrin-costimulated T cells express CTLA-4 and can be
      costimulated via CTLA-4. Optimal development of various immune functions may
      involve combined costimulation via both CD28 and CTLA-4.

PMID- 7511624
TI  - IL-12 influences intrathymic T cell development.
AB  - IL-12 has been implicated in the maturation and activation of peripheral T
      lymphocytes and NK cells. In the present study we have investigated the potential
      role of IL-12 in intrathymic T cell development. Treatment of mouse fetal thymic
      organ culture with IL-12 caused a significant reduction in size and cell number
      compared with the untreated controls. Flow cytometric analysis of the thymocytes
      recovered from these lobes showed differential effects on individual thymocyte
      subsets, most but not all of which were significantly decreased. In contrast,
      however, we observed an increase in both the percentage and cell number of alpha
      beta TCR+CD4-CD8+ thymocytes. This effect could be neutralized with an anti-IL-12
      antibody, demonstrating the specificity of the influence of IL-12 in the fetal
      thymic organ culture system. IL-12 caused proliferation of isolated thymocyte
      subsets, particularly CD3+CD4-CD8+ cells in the presence of IL-2 and IL-4.
      Additionally, IL-12 induced significant proliferation of early CD3-CD4-CD8-
      triple negative CD44+CD25+ pro-T cells in combination with stem cell factor. We
      show that both the p35 and p40 chains of IL-12 are produced in the fetal and
      adult mouse thymus and that thymic stromal cells are a potential source of this
      cytokine.

PMID- 7511625
TI  - Mechanism of lymphocyte function-associated molecule 3-Ig fusion proteins
      inhibition of T cell responses. Structure/function analysis in vitro and in human
      CD2 transgenic mice.
AB  - Soluble ligands specific for cell surface molecules involved in APC-T cell
      interactions can signal cells and modulate immune responses. Recently, we
      reported that LFA3TIP, a fusion protein comprised of the first LFA-3
      extracellular domain fused to the hinge, CH2, and CH3 regions of a human IgG1
      inhibits proliferation of human T cells in vitro. We report herein the cell-based
      mechanism(s) of LFA3TIP in inhibition by studying the effects of structurally
      altered LFA3-Ig fusion proteins on proliferation of human PBL in vitro and on
      responses of mice transgenic for human CD2. We show that LFA3TIP inhibition
      requires expression of both the LFA-3 and CH2 domains of the fusion protein that
      bind CD2 and Fc gamma RI or Fc gamma RIII, respectively. LFA3TIP forms an
      intracellular Fc gamma R/CD2 bridge and directs cytolysis of CD2+ cells by
      freshly drawn human PBL in vitro as well as the non-C-mediated depletion of
      peripheral T cells of human CD2 transgenic mice. The cell-based mechanism(s) of
      LFA3TIP inhibition are discussed.

PMID- 7511626
TI  - CD9-regulated adhesion. Anti-CD9 monoclonal antibody induce pre-B cell adhesion
      to bone marrow fibroblasts through de novo recognition of fibronectin.
AB  - The modulation of adhesive interaction between lymphocyte progenitors and bone
      marrow stroma may critically determine the maturation and migration of B cell
      progenitors. mAb against CD9 and beta 1 integrins are reported to induce the
      homotypic adhesion of pre-B cells. We present evidence that the anti-CD9 mAb
      50H.19 and ALB6 but not the proaggregatory anti-VLA-4 mAb 44H6 also enhance the
      Fc-independent heterotypic adhesion of the human pre-B cell lines NALM-6 and HOON
      to bone-marrow stromal fibroblasts (BM-FB) but not to bone marrow stroma. CD9
      enhanced binding of NALM-6 cells to BM-FB was inhibited 58% by the anti-VLA-4 mAb
      HP2/1, 36% by the anti-VLA-5 mAb BIIG2, and 99% by their combination. The mAb
      effectively inhibited adhesion when prebound to NALM-6 cells but not when
      prebound to BM-FB. The anti-VCAM-1 mAb E1/6 inhibited CD9-enhanced adhesion by
      only 14% suggesting the involvement of other ligands. Adhesion was inhibited by
      mAbs against the COOH-terminus and central cell binding domains of fibronectin,
      as well as by the corresponding CS1 and RGD peptides. Adhesion was not affected
      by H-7 and sphingosine, inhibitors of protein kinase C. These results suggest
      that perturbation of CD9 on pre-B cells promotes recognition of stromal cell
      fibronectin by VLA-4 and VLA-5 and implicates CD9 as a novel regulator of inside
      out signaling relevant to B lymphopoiesis.

PMID- 7511627
TI  - Antibody repertoire in the response to a protein antigen. Interrelated idiotypic
      families in the response to Ia.7.
AB  - Mouse alloantibodies to Ia.7 display a cross-reactive idiotype (CRI) recognized
      by xenogeneic anti-idiotypes. The CRI is expressed on serum Abs in all responding
      individuals and on all anti-Ia.7 mAbs, from mice of appropriate genetic types. In
      addition, both xenogeneic and allogeneic anti-idiotypes in this system have a
      striking ability to induce Ia.7-specific responses in mice never exposed to the
      Ag. Because of these unusual features, we have investigated the biologic and
      structural basis of the idiotypic sharing in this system. Ia.7-specific Ab
      populations induced by eight different Ab2 mAbs were analyzed for expression of
      each of the set of idiotopes. Two obvious explanations for the unusual properties
      of the system do not appear to be correct. 1) The induction of Ag-specific
      immunity was not caused by internal imagery; and 2) the Ab2s do not simply
      recognize the same idiotope, because they induce populations that were found to
      be distinct in idiotope expression. The biologic properties of the system are
      instead caused by a pattern of expression of idiotope sets on distinct but
      related Ab families, and a remarkable linkage of a series of different idiotopes
      to Ia.7-specific activity. Mouse anti-idiotypic responses failed to recognize the
      widely shared CRI site, even when sequential immunizations were performed. To
      examine the structural basis of Id sharing, light chains of three CRI+ mAbs were
      sequenced. They were found to be extremely homologous to each other and to the
      germ-line V kappa 21E gene, and they used either J1 or J2. A model containing
      families of distinct but related V regions is proposed for the anti-Ia.7
      repertoire.

PMID- 7511628
TI  - Monoclonal, antigen-specific, T cell contrasuppressor factor expresses
      determinants of TCR alpha-chain (not necessarily TCR beta-chain), having a
      molecular mass of about 40 kDa.
AB  - Contrasuppression is a regulatory T cell activity that acts on helper and contact
      sensitivity effector T cells to protect them from the action of suppressor T
      cells. In this study, we examined a monoclonal Ag-specific T cell-secreted
      contrasuppressor factor (TcsF) with Ag specificity for the hapten TNP
      (trinitrophenyl). This factor positively influences the adoptive cell transfer of
      contact sensitivity in the presence of active suppression. Results presented in
      this report demonstrate a relationship between TcsF and the alpha,beta-T cell
      receptor (TCR). We found that TcsF bound to mAb anti-TCR-alpha (H28) and to mAb
      anti-TCR-beta (H57) immunoaffinity columns, but not to a mAb anti-TCR-gamma,delta
      (UC7) column. The bound contrasuppressor activity could be recovered from these
      affinity columns by base elution. Reduction of TcsF with DTT followed by
      alkylation with methylmethanethiosulfonate (MMTS), demonstrated that the active
      subunit of TcsF bound to and eluted from anti-TCR-alpha, but not to anti-TCR-beta
      columns. The active TcsF that bound to anti-TCR-alpha but not to the anti-TCR
      beta column was shown subsequently to have the ability to bind to specific Ag
      columns TNP-BSA and TNP-BGG Sepharose 4B. The TcsF could be successfully
      recovered later from Ag columns; thus suggesting that the Ag-binding domain for
      mAb, and the biologic activity, resides on the TCR-alpha chain of TcsF.
      Separation of TcsF on SDS-PAGE under reducing conditions, followed by elution and
      renaturation of proteins from the gel slices, showed that a 35 to 40 kDa protein
      had the T cell contrasuppressive activity. Western blot analysis of nonreduced
      TNP-binding TcsF revealed TCR-alpha,beta determinants on an 80-kDa native
      molecule similar to TCR-alpha,beta from a helper T cell clone. In summary, Ag
      specific, Ag-binding T cell-derived contrasuppressor factor has serologic
      determinants of TCR-alpha and TCR-beta chains, but the TCR-alpha chain and not
      the TCR-beta chain is required for biologic function. This TCR-alpha determinant
      containing factor is absorbed by specific Ag (TNP) columns. SDS-PAGE analysis
      under reducing conditions suggested a molecular weight of about 35 to 40 kDa for
      the TNP-specific TcsF. The mechanism of action of the TCR-alpha-containing
      contrasuppressor factor in the regulation contact sensitivity is discussed.

PMID- 7511629
TI  - Hypercross-linking surface IgM or IgD receptors on mature B cells induces
      apoptosis that is reversed by costimulation with IL-4 and anti-CD40.
AB  - Cross-linking of sIgM or sIgD receptors on mature B cells with appropriate anti
      Ig Abs normally induces B cell activation and DNA synthesis. We show here that
      hypercross-linking of either class of sIg receptor on these cells by
      biotinylated, normally mitogenic anti-mu or anti-delta mAb by avidin rapidly
      induces unresponsiveness to heterologous anti-Ig, accompanied by DNA
      fragmentation characteristic of apoptosis. Apoptotic nuclei can be detected
      within 4 h after stimulation, but cells that survive for 12 to 16 h are
      abortively activated, as evidenced by increased levels of MHC class II Ags.
      Because the induction of B cell tolerance is known to be modulated by T cell
      derived influences, we investigated the effects of two stimuli--IL-4 and ligation
      of CD40--that are known to affect B cell survival in this system. IL-4 partially
      reversed the induction of apoptosis, as did a mAb to CD40, and both reagents
      together caused almost complete reversal. We therefore conclude that in the
      absence of T cell help the extent of sIg receptor cross-linking on mature B cells
      determines whether the cells enter cycle or become deleted. We believe that this
      system represents a polyclonal model of clonal deletion of mature B cells induced
      by highly cross-linking Ags, such as type 2 T-independent polysaccharide Ags.

PMID- 7511630
TI  - c-kit expression by B cell precursors in mouse bone marrow. Stimulation of B cell
      genesis by in vivo treatment with anti-c-kit antibody.
AB  - To examine the in vivo role of c-kit receptor in B lymphopoiesis we have
      evaluated precursor B cell populations expressing c-kit in mouse bone marrow and
      the effects on B cell genesis of administering a neutralizing anti-c-kit mAb,
      ACK2. Double immunofluorescence labeling and mitotic arrest were used to examine
      bone marrow cells from BALB/c mice. Almost one-half of TdT+ cells and one-quarter
      of B220+ cells coexpressed c-kit, mainly at low intensities, and were actively
      proliferating in vivo. c-kit+ cells that lacked B lineage markers expressed c-kit
      in high intensities and entered mitosis at an exceptionally rapid rate. In ACK2
      treated mice, erythroid and granulocytic cells were almost completely absent from
      the bone marrow, whereas, in contrast, B lymphopoiesis was stimulated. Pre-B
      cells expressing cytoplasmic mu-chains; as well as TdT+B220+ cells before mu
      expression, were increased two- to fourfold in number and production rate. IgM
      bearing B lymphocytes were increased in bone marrow and spleen. The results
      demonstrate that many early precursor B cells in mouse bone marrow constitutively
      express c-kit receptor. The failure of ACK2 treatment to block B lymphopoiesis,
      however, suggests that c-kit receptor function is not essential for precursor B
      cell development in vivo, but can be replaced by alternative signaling systems.
      The stimulation of B cell genesis by ACK2 treatment may reflect a conferred
      advantage in the competition for microenvironmental factors which underlies the
      balance between B lymphopoiesis and other hemopoietic lineages in vivo.

PMID- 7511631
TI  - Unique selection determinant in polyclonal V delta 2-J delta 1 junctional regions
      of human peripheral gamma delta T lymphocytes.
AB  - Human peripheral gamma delta T lymphocytes are characterized by the preferential
      expression of a TCR consisting of a V delta 2-J delta 1-C delta chain and a V
      gamma 9-J gamma 1.2-C gamma 1 chain, which are virtually absent on thymocytes.
      Here we report the identification of a unique selection determinant that is
      located in the polyclonal V delta 2-J delta 1 junctional regions of peripheral
      gamma delta T lymphocytes. The selection determinant was discovered by the
      presence of an invariant T nucleotide at the relative second position of the V
      delta 2-J delta 1 junctional regions of peripheral polyclonal gamma delta T
      lymphocytes. Comparison of published sequences from peripheral gamma delta T
      lymphocytes confirmed the presence of this invariant T nucleotide (90%) in
      healthy individuals and in patients with various diseases. Translation of the
      relative first codon of the V delta 2-J delta 1 junctional regions revealed
      strikingly high frequencies of the homologous hydrophobic amino acids leucine
      (46%), valine (35%), and isoleucine (5%) at this position. The invariant T
      nucleotide was absent in polyclonal thymocytes and out-of-frame V delta 2-J delta
      1 junctional regions, which proves that selection occurred at the protein level
      and not at the genomic level. No selection determinant could be identified in V
      gamma 9-J gamma 1.2 junctional regions, but the frequently occurring invariable,
      so-called canonical junctional region provided evidence for biased recombination
      processes. Although the obtained data do not allow discrimination between thymic
      selection and/or peripheral Ag-driven expansion, the identification of a strong
      selection determinant consisting of only one amino acid at a fixed position in V
      delta 2-J delta 1 junctional regions of virtually all peripheral polyclonal V
      delta 2/V gamma 9 T lymphocytes provides a new perception of TCR specificity and
      selection processes at the TCR protein level.

PMID- 7511633
TI  - Functional analysis of two tetanus toxin universal T cell epitopes in their
      interaction with DR1101 and DR1104 alleles.
AB  - In this study we have investigated the interaction between two DR11 alleles
      (DB*1101 and DB*1104) and two previously described tetanus toxin (tt) universal T
      cell epitopes P2(tt830-843) and P30(tt947-967) by means of a functional cytotoxic
      competition assay. Both truncation analysis and single alanine substitution
      analysis were performed. In addition, the capacity of truncated and single
      alanine substituted peptides to be recognized by human T cell clones from donors
      bearing the DR1101 or DR1104 alleles was assessed. In the case of truncated
      peptides the same binding and recognition pattern was observed with both alleles.
      Longer peptides were better competitors and more potent stimulators, a result
      that should be taken into account when these peptides are used as immunogens.
      None of the single alanine substitutions could abrogate or strongly diminish the
      inhibitory capacity of the analogues tested indicating the lack of strong "anchor
      residues" present in P2 and P30 and implicated in DR binding. In addition,
      although the original peptide sequences were presented to specific T cell clones
      with comparable efficiency, some of the alanine single substituted peptides were
      better recognized in association with one of the alleles by clones derived from
      individuals bearing the homologous allele. The only exception was the tt951-967
      analogue ttW955A, which was preferentially recognized in association with the
      DR1104 allele regardless of the clone tested. This suggests that, although it
      binds to both alleles with comparable efficiency, the MHC-peptide complex so
      formed is conformationally distinguishable by specific T cell clones.

PMID- 7511632
TI  - Immunologic and molecular characterization of Amb p V allergens from Ambrosia
      psilostachya (western Ragweed) pollen.
AB  - We have purified and characterized the Amb p V allergen (A1 variant) from western
      ragweed (Ambrosia psilostachya) pollen. This allergen was found to be highly
      cross-reactive with the Amb a VA1 allergen from short ragweed (A. artemisiifolia)
      pollen in a competitive double-Ab radioimmunoassay (DARIA) and the two allergens
      showed concordant allergenic potency in histamine-release experiments. We cloned
      and sequenced several Amb p V genes from western ragweed pollen and flowers by
      direct PCR of genomic DNA. The amino acid sequences deduced from the nucleotide
      sequences indicated the presence of multiple forms of Amb p V that could be
      broadly classified into two groups: Amb p VA and Amb p VB variants. The sequences
      of the Amb p VA variants are highly homologous to Amb a V (about 90% identity)
      and very similar to the protein sequence that we obtained. The Amb p VB variants
      share approximately 65% amino acid homology with Amb a V and have five to seven
      cysteine residues as compared with the eight found in Amb a V and Amb t V. Two
      cysteine residues that form disulfide bonds in other Amb Vs (positions 19 and 43
      in Amb a V) are replaced by serine and alanine in the Amb p VB1 and Amb p VB2
      variants. We have generated model structures of Amb p VA1, VA2, VA3, and VB1
      variants from the nuclear magnetic resonance-derived structure of Amb a VA1 by
      homology modeling. Comparison of antigenic epitopes predicted for the structures
      of Amb p V variants and Amb a VA1 explains the observed cross-reactivity of the
      two ragweed proteins and suggests the epitopes likely to be involved in Ab
      recognition.

PMID- 7511634
TI  - In vitro and in vivo effects of lymphokine-activated killer cells upon
      preattachment ovine conceptuses.
AB  - An investigation assessed the cytolytic effect of autologous ovine lymphokine
      activated killer (LAK) cells upon preattachment ovine conceptuses. For an in
      vitro experiment, conceptuses were recovered from six ewes on each of days 14,
      16, and 19 (estrus = day 0). Dissociated conceptus cells (5 x 10(4), considered
      target cells) were incubated with autologous LAK cells at varying E:T ratios (5:1
      200:1) and cytotoxicity was assessed by 51Cr release. In vivo, control (saline),
      cultured PBL (1 x 10(7)) and LAK cells (1- and 4- x 10(7)) were infused into the
      lumen of the uterine horn ipsilateral to the corpus luteum of mated ewes on day
      14. Conceptuses were recovered on day 19 and placed within one of three
      morphologic categories (intact, large fragments, or highly fragmented). The
      numbers of mononucleated and binucleated giant cells and remaining trophoblastic
      cells were then quantitated within sections of conceptus tissue. Mitotic activity
      was also recorded. At E:T ratios of 100:1 and 200:1, respectively, percent 51Cr
      release for LAK cell cultures was greater (p < 0.05) for day-16 and 19- than day
      14 conceptus cells. The frequencies of highly fragmented conceptuses recovered
      from saline + cultured PBL and LAK cell-infused ewes were 0/10 and 8/13,
      respectively. Within tissue sections, the numbers of morphologically normal
      mononucleated giant and mitotic cells were less (p < 0.05) for LAK cell (4 x
      10(7)) than for saline-infused ewes. Data from additional in vitro and in vivo
      experiments revealed that supernatants from LAK cell (4 x 10(7)) cultures failed
      (p > 0.05) to affect % 51Cr release from K-562 target cells, conceptus
      morphology, and numbers of conceptus cells. In conclusion, autologous LAK cells
      exerted in vitro and in vivo lytic damage upon preattachment ovine conceptuses. A
      temporal pattern was observed for the in vitro lytic responses.

PMID- 7511635
TI  - Monocytes express a non-neurokinin substance P receptor that is functionally
      coupled to MAP kinase.
AB  - The data presented in this paper demonstrate a new substance P (SP) binding site
      that is expressed on human monocytes. The apparent dissociation constant (Kd) for
      binding of 125I-labeled Bolton Hunter-SP (125I-BH-SP) to the receptor on monocyte
      membranes is 2.24 +/- 0.9 x 10(-7) M and the maximum binding capacity (Bmax) is
      4.7 +/- 0.5 pmol/mg membrane protein. It could be excluded that this receptor is
      one of the known neurokinin (NK) type of receptors on the basis of binding
      characteristics for NK1, NK2, and NK3 agonists. Moreover, we demonstrate that the
      binding site is neither the bombesin receptor nor the serpin enzyme complex
      receptor nor the FMLP receptor. The order of potency for inhibition of 125I-BH-SP
      binding to the receptor on monocyte membranes is NK1 antagonist [D-Pro2,D
      Trp7,9]SP > SP > NK3 agonist [MePhe7]SP > bombesin. Cross-linking studies with
      disuccinimidylsuberate, followed by SDS-PAGE analysis, revealed that 125I-BH-SP
      is specifically bound to a membrane protein with an apparent molecular mass of 47
      kDa. At a functional level, SP induces the activation of MAP kinase in human
      monocytes. The ED50 for activation of MAP kinase positively correlated (r =
      0.999, p < 0.0005) with the apparent affinity of the ligands applied in the 125I
      BH-SP displacement studies. From these results, we conclude that this SP binding
      site on monocytes is a non-NK receptor protein that is functionally linked to the
      activation of MAP kinase.

PMID- 7511636
TI  - Leukocyte recruitment into human skin transplanted onto severe combined
      immunodeficient mice induced by TNF-alpha is dependent on E-selectin.
AB  - In order to study the in vivo role of E-selectin in human inflammation, we have
      developed a model in which human skin is transplanted onto severe combined
      immunodeficient (SCID) mice. The grafted skin closely resembles normal skin and
      retains its human vasculature. After intradermal injection of rTNF-alpha, human E
      selectin was rapidly up-regulated on dermal microvessels, with significant
      expression (determined immunohistochemically) at 1 h postinjection and maximum
      expression at 2 h postinjection. To study the functional role of E-selectin, a
      murine Ab against human E-selectin (mAb HEL 3/2) was developed that inhibited the
      in vitro adhesion of both human U937 cells and murine 32D cells to TNF-alpha
      stimulated human endothelial cells. After intradermal injection of TNF-alpha,
      large numbers of murine leukocytes migrated into the grafts within 2 h.
      Intravenous injection of the antihuman E-selectin mAb 3/2 completely inhibited
      murine white blood cell (WBC) transmigration into the skin grafts, but an isotype
      matched control Ab that also bound to human endothelium had no effect. Antihuman
      E-selectin mAb 3/2 was also able to inhibit the migration of i.v. 51Cr-labeled
      human neutrophils. These findings demonstrate that E-selectin is important in
      early white blood cell adhesion events and is required for TNF-alpha-induced
      white blood cell transmigration in the human/SCID mouse chimeric model.

PMID- 7511637
TI  - Selective expansion of cytotoxic T lymphocytes with a CD4+CD56+ surface phenotype
      and a T helper type 1 profile of cytokine secretion in the liver of patients
      chronically infected with Hepatitis B virus.
AB  - Highly purified CD4+ T cells isolated from liver biopsies of patients with
      hepatitis B virus-induced CAH had a strong cytotoxic activity and were comprised
      of a substantial number of cells (25%-40%) expressing CD56 surface marker. These
      cells were absent in CD4+ T cells from the peripheral blood of CAH patients or
      normal controls and these suspensions did not have cytotoxic activity. CD4+CD56+
      T cells were further characterized by studies at the clonal level. A total of 71
      hepatitis B envelope antigen-specific CD4+ T cell clones was investigated (23
      from liver biopsies, 48 from peripheral blood of patients or normal vaccinated
      individuals). A total of 16 out of 23 (69.5%) of the clones from liver biopsies,
      but only 4.1% (2 out of 48) of those from PBLs, expressed CD56. A clone was
      defined as CD56+ when 40% or more of the cells expressed the marker. Production
      of TNF-alpha, IL-4, IL-5, IL-2, and IFN-gamma was investigated in 15 CD4+CD56+
      and in 18 CD4+CD56- T cell clones, which shared the same HLA restriction element
      (DR2w15) and the same fine specificity (peptide 193-207 of the S region). All of
      the clones from the two groups released TNF-alpha and IL-2. However, all of the
      CD4+CD56+ T cell clones produced IFN-gamma but not IL-4 and IL-5 (Th1-like cell
      clones). Fourteen of the CD4+CD56- clones released IFN-gamma, IL-4, and IL-5 (Th0
      like cell clones); three produced IL-4 and IL-5 but not IFN-gamma (Th2-like cell
      clones); and only one had a Th1 cytokine secretion profile. Cell fractionating
      studies within single CD4+CD56+ T cell clones showed that cells expressing high
      density CD56 had a stronger cytotoxic activity and produced higher levels of IFN
      gamma than cells with low density CD56, thus further supporting a correlation
      between CD56 expression and cell functions. The results indicate that: 1) in CAH
      patients, cytotoxic CD4+ T cells with a Th1 cytokine secretion profile are
      compartmentalized in the liver, 2) these cells may be identified by the
      expression of CD56, 3) the expansion of these cells may be facilitated by
      antigenic stimulation within the inflammatory environment of the liver, and 4)
      CD4+CD56+ cells may play a pathogenetic role in hepatitis B virus infection.

PMID- 7511638
TI  - Characterization of the T cell determinants in the induction of autoimmune
      arthritis by bovine alpha 1(II)-CB11 in H-2q mice.
AB  - Collagen-induced arthritis (CIA) is an experimental autoimmune disease elicited
      in genetically susceptible strains of mice by immunization with heterologous type
      II collagen. This experimental disease is mediated by the immune response of both
      T and B cells, and susceptibility is restricted by the class II molecules of the
      MHC. To study the T cell determinants of bovine type II collagen (CII) that
      mediate the autoimmune response in H-2q mice, we have identified a cyanogen
      bromide fragment of bovine CII, CII(124-402), that induces arthritis in DBA/1
      mice. Using an overlapping set of peptides to map the T cell response to CII(124
      402), we have determined that the I-Aq-restricted T cell response to this
      collagen fragment is mediated by a single immunodominant antigenic determinant.
      Consequently, this determinant plays a central role in promoting the production
      of the collagen-specific Abs and the induction of CIA in H-2q mice.
      Characterization of this immunodominant determinant revealed that the core
      residues required for T cell stimulation consists of only eight amino acids and
      is located at amino acids 260 through 267 of bovine CII. The systematic analysis
      of the contribution of each of these amino acids, in conjunction with sequences
      of other peptides known to bind to I-Aq, have allowed us to propose a peptide
      binding motif for the collagen arthritis susceptibility allele, I-Aq.

PMID- 7511639
TI  - New monoclonal antibody (23D12) recognizing three different V gamma elements of
      the human gamma delta T cell receptor. 23D12+ cells comprise a major
      subpopulation of gamma delta T cells in postnatal thymus.
AB  - The gamma delta TCR is expressed on 1 to 5% of CD3+ human peripheral blood T
      lymphocytes. The majority of peripheral blood gamma delta T cells expresses V
      gamma 9 paired with V delta 2; this subset strongly responds to certain microbial
      ligands. Other gamma delta T cell subsets with unknown Ag specificity expressing
      different V gamma elements are present in peripheral blood and lymphoid tissue.
      We describe a new anti-human V gamma mAb termed 23D12 with unusual specificity.
      As revealed by analysis of a large number of T cell clones and transfectants
      expressing molecularly well-defined gamma delta TCR, mAb 23D12 recognized
      several, but not all, members of the human V gamma 1 family, specifically V gamma
      2, V gamma 3, and V gamma 4 but not V gamma 5 or V gamma 8. In combination with
      available mAb against V gamma 4, mAb 23D12 was used to identify V gamma 2- or V
      gamma 3-bearing cells. On average, 23D12+ cells accounted for 18% of peripheral
      blood gamma delta T cells and 56% of postnatal gamma delta thymocytes. In
      combination with anti-V gamma 9 mAb, mAb 23D12 23D12 identified gamma delta cells
      expressing V elements other than V gamma 2, V gamma 3, V gamma 4, or V gamma 9.
      Such cells are detectable in peripheral blood and postnatal thymus. Using mAb
      23D12, we also confirmed the appearance of two distinct TCR gamma-chains on the
      surface of some gamma delta T cells.

PMID- 7511641
TI  - Cell calcium signaling via GM1 cell surface gangliosides in the human Jurkat T
      cell line.
AB  - The cell surface ganglioside GM1 is the specific receptor for the B subunit of
      cholera toxin. We show here that in the human Jurkat T cell line an increase in
      intracellular free Ca2+ concentration can be elicited by using B subunits to
      ligate GM1 molecules. This Ca2+ signaling effect is clearly mediated through GM1
      because it can be observed after direct insertion of exogenous GM1 in a Jurkat
      cell variant deficient in GM1 expression. The observed Ca2+ response clearly
      involves both the release of Ca2+ from intracellular stores and a Ca2+ influx
      from extracellular spaces. It is sustained in the presence of 1 mM extracellular
      Ca2+, whereas it becomes transient in Ca(2+)-free medium. We show that the GM1
      mediated stimulation partially empties the CD3-dependent and inositol 1,4,5
      trisphosphate-sensitive intracellular Ca2+ pool suggesting a dependence of the
      Ca2+ response from activation of phospholipase C (PLC) metabolism. Accordingly,
      tyrosine phosphorylation of PLC gamma-1 can be evidenced but only in Jurkat cells
      highly expressing GM1. GM1 stimulation results in an IL-2 production comparable
      to that obtained after CD3 activation. Finally, the GM1-linked cell Ca2+
      activation pathway is also observed in a Jurkat cell clone lacking Ag-specific
      receptor expression suggesting that the presence of functional CD3/TCR molecules
      is not essential for GM1-induced cell Ca2+ response. Altogether, these data show
      that cell surface gangliosides GM1 may act as a signaling molecule in Jurkat T
      cells possibly by a new pathway, a finding of importance when considering a
      possible function for ubiquitous membrane carbohydrate structures in T cell
      recognition systems.

PMID- 7511642
TI  - Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo.
AB  - Lymphocyte recirculation through different organs is thought to be regulated by
      adhesion molecules ("homing receptors") recognizing tissue-specific vascular
      addressins on endothelium. Here we show that the alpha 4/beta 7-integrin has a
      key role in the migration of mouse lymphocytes to mucosal sites. Homing to
      Peyer's patches but not to peripheral lymph nodes is inhibited by Fab fragments
      of mAb PS/2 against the alpha 4-integrin chain, by mAb DATK32 recognizing a
      combinatorial epitope on the alpha 4/beta 7-integrin, and by mAb FIB30 against
      the beta 7-chain. The Abs significantly reduce homing of lymphocytes to the
      intestine, as well. The migration of immunoblasts to gut and gut-associated
      lymphoid tissue also involves the alpha 4/beta 7-integrin heterodimer. Another
      anti-alpha 4 Ab, R1-2, which blocks lymphocyte binding to Peyer's patches in the
      Stamper-Woodruff frozen section assay and lymphocyte adhesion to VCAM-1 and
      fibronectin, has only minor effects on lymphocyte traffic in vivo. Anti-VCAM-1 Ab
      as well as the fibronectin peptide CS-1 are without influence on the migration to
      Peyer's patches or intestine, in contrast to Ab against the mucosal addressin
      MAdCAM-1. Thus, homing to gut-associated sites is regulated by the alpha 4/beta 7
      integrin heterodimer interacting with the vascular addressin, MAdCAM-1, and not
      with fibronectin or VCAM-1 as counterstructures. Inhibition of homing to Peyer's
      patches and intestine by the anti-integrin Abs studied was only partial. L
      selectin also participates in the homing of small lymphocytes to mucosal sites,
      especially Peyer's patches, but does not contribute substantially to the
      localization of blasts into the intestinal wall. The results support a major, but
      not exclusive role of the alpha 4/beta 7-integrin in lymphocyte traffic to
      mucosal sites.

PMID- 7511643
TI  - Tyrosine kinase and CD45 tyrosine phosphatase activity mediate p21ras activation
      in B cells stimulated through the antigen receptor.
AB  - Cross-linking of the Ag receptor (AgR) induces intracellular signaling events in
      B cells, such as p21ras activation, that lead to their proliferation and
      differentiation. This event is accompanied by the tyrosine phosphorylation of the
      p21ras-associated GTPase-activating protein p120 ras.GAP, raising the possibility
      that AgR-stimulated p21ras activity is regulated by protein tyrosine kinases
      (PTKs) and protein tyrosine phosphatases (PTPases) in B cells. To test this
      possibility, we examined the effects of PTK and PTPase inhibitors on protein
      tyrosine phosphorylation and p21ras activation induced by AgR cross-linking in
      TNP-specific TA3 7.9 murine B lymphoma cells. Although AgR-induced protein
      tyrosine phosphorylation was inhibited by the PTK inhibitors genistein and
      herbimycin A, it was enhanced by exposure to the PTPase inhibitor phenylarsine
      oxide (PAO). Cross-linking of the AgR by Ag or F(ab')2 anti-IgM induced a rapid
      (within 5 min) two- to threefold increase in p21ras activation in 7.9 B cells.
      Interestingly, a second peak of p21ras activation was evident at approximately 40
      min after stimulation. Genistein and herbimycin A and PAO each blocked AgR
      stimulated p21ras activation. Similarly, Ag-induced p21ras activation was
      inhibited by pretreatment of 7.9 B cells with an anti-CD45 mAb (detects the 220
      kDa B cell isoform of CD45). Moreover, p21ras activation was induced by Ag and
      F(ab')2 anti-IgM in CD45+ but not CD45- J558L microns 3 B cells. These data
      indicate that p21ras activation induced by AgR cross-linking in B cells is
      regulated by both PTK and CD45 PTPase activities.

PMID- 7511640
TI  - B7 expression on thymic medullary epithelium correlates with epithelium-mediated
      deletion of V beta 5+ thymocytes.
AB  - Recent evidence suggests that I-E+ thymic epithelium, especially medullary
      epithelium, can induce partial deletion of superantigen-reactive T cells
      expressing TcR V beta 5, V beta 11, and V beta 17. To seek further information on
      this issue, we constructed bone marrow chimeras in which MHC class II I-E is
      expressed on thymic epithelial cells at various levels and locations; the
      chimeras were reconstituted with stem cells from TcR V beta 5 transgenic mice.
      Intrathymic deletion of V beta 5 T cells was restricted to relatively mature T
      cells (expressing high TcR levels), and the degree of deletion correlated with
      the density of I-E expression in the thymic medulla rather than in the thymic
      cortex; selective I-E expression in medullary epithelium caused prominent
      deletion. Interestingly, immunostaining of normal and chimeric mice revealed that
      expression of B7 (the ligand for CD28) is largely restricted to a subset of
      medullary epithelial cells; these cells are I-E+ and co-express a specific
      carbohydrate bound by the lectin UEA-1. B7 expression was lower in thymuses of
      class II-deficient mice (A beta b-/-) and T-cell-deficient mice (SCID),
      suggesting that B7 expression is up-regulated during CD4+ thymocyte selection. In
      support of this idea, B7 expression in the thymus was restored to a normal level
      in bone marrow reconstituted SCID mice. Because B7 expression correlates with a
      costimulatory signal for T cells, selective expression of B7 and related antigens
      on I-E+ medullary epithelium may explain why these cells play a more prominent
      role in V beta deletion than cortical epithelium.

PMID- 7511644
TI  - CD28-mediated costimulation is necessary for optimal proliferation of murine NK
      cells.
AB  - CD28, a cell surface molecule expressed on all murine T cells, plays a critical
      role in T cell activation. We show here that NK-1.1+ cells, a subpopulation of
      SCID splenocytes, and IL-2-activated NK cells express CD28, although at lower
      levels than alpha beta T cells. Optimal proliferation of highly purified asialo
      GM1+ NK cells from the SCID spleen was observed in response to stimulation with
      IL-2 and PMA, together with anti-CD28 or L-B7+ cells. Thus, in addition to IL-2,
      murine NK cells require CD28-mediated costimulatory signals for optimal
      proliferation. IL-2-activated NK cells produced enhanced levels of IFN-gamma and
      TNF in response to stimulation with anti-CD28 and PMA. On the other hand, we were
      unable to demonstrate that CD28 signaling had any effect on NK-mediated
      cytotoxicity. We conclude that the CD28 costimulatory pathway is functional in NK
      cells and plays an important role in their proliferation and cytokine production.

PMID- 7511645
TI  - Assessment of CD4 expression by early T precursor cells and by dendritic cells in
      the human thymus.
AB  - The adult mouse thymus contains a minute population of early lymphoid precursor
      cells that express moderate levels of CD4. We searched for a corresponding
      population of early T precursors in the infant human thymus, by first depleting
      the majority of more mature thymocytes, then using immunofluorescence and flow
      cytometry to analyze cells bearing a range of early T lineage markers. No
      discrete population of early T precursors expressing CD4 was observed, in
      contrast to the murine thymus. Most putative very early human thymocytes were CD4
      8-3-1-2lo44+34+7hi class I MHChi class II MHC-. However, a distinct population of
      human thymic dendritic cells expressing high levels of CD4 was isolated. These
      were CD4hi8-3-1-2-44+34-7- class I MHChi class II MHChi, and lacked markers of B
      cells, NK cells, or myeloid cells. They were large cells that exhibited dendritic
      morphology after brief periods of culture, and they were efficient stimulators of
      allogeneic T cells. The biologic implications of CD4 expression by thymic
      dendritic cells are discussed.

PMID- 7511646
TI  - Function of adhesion molecules lymphocyte function-associated antigen-3 and
      intercellular adhesion molecule-1 on human epidermal Langerhans cells in antigen
      specific T cell activation.
AB  - In addition to the interaction between the TCR and the MHC/Ag complex on the APC,
      optimal T cell activation also requires interaction between adhesion molecules on
      the APC and their ligands on T cells. We determined the presence of adhesion
      molecules on human epidermal Langerhans cells (LC) and their role in Ag-specific
      T cell activation. Freshly isolated LC did not display ICAM-1 (CD54), ICAM-2, LFA
      1 (CD11a), and LFA-3 (CD58), as detected by double-color FACS analysis, using HLA
      DR expression for LC identification. Upon culture, LC clearly expressed ICAM-1
      and LFA-3, both already detectable after 1 day, reaching a plateau at day 2. ICAM
      2 and LFA-1 were undetectable on cultured LC and attempts to induce this
      expression by different culture conditions remained unsuccessful. mAb against
      ICAM-1, LFA-1, LFA-3, and CD2, continuously present during culture, inhibited the
      T cell proliferative response to Candida albicans presented by cultured LC.
      Pretreatment of LC and/or T cells with mAb indicated that anti-ICAM-1 and anti
      LFA-3 inhibited at the LC level, whereas anti-LFA-1 and anti-CD2 inhibited at the
      T cell level. The mAb-induced inhibition was dose-dependent, but a total blockade
      of the response was never achieved. Time-course observations revealed that ICAM-1
      and LFA-3 on LC only functioned during the initiation phase of T cell activation.
      Our study demonstrates that both ICAM-1 and LFA-3 on LC considerably contribute
      to the generation of a T cell response. The high expression of these accessory
      molecules enable LC, at least in part, to perform their powerful Ag-presenting
      function.

PMID- 7511647
TI  - Expression of a hybrid complement regulatory protein, membrane cofactor protein
      decay accelerating factor on Chinese hamster ovary. Comparison of its regulatory
      effect with those of decay accelerating factor and membrane cofactor protein.
AB  - C activation on the cell surface is supposedly regulated by membrane cofactor
      protein (MCP) and decay accelerating factor (DAF). These are complementary in
      function: MCP acts as a cofactor in factor I-mediated C3b and C4b inactivation,
      thus preventing the assembly of C3 convertases, whereas DAF accelerates
      spontaneous decay of the assembled C3 convertase. In this report, a hybrid MCP
      DAF was expressed on Chinese hamster ovary cells by transfecting cDNA, and its
      regulatory activity was compared with those of MCP and DAF transfectants and with
      a transfectant expressing both MCP and DAF (MCP + DAF). The C3 deposition on
      sensitized CHO cells through activation of the classical pathway was blocked to a
      different degree with these transfectants, the order being MCP + DAF > DAF >
      hybrid MCP-DAF > MCP. Likewise, the C3 deposition via the alternative pathway was
      blocked efficiently in the order hybrid > MCP + DAF > MCP. The C-mediated
      cytolysis of CHO cells virtually reflected the degree of C3 fragment deposition.
      The MCP-DAF transfectant acquired additive protective activity against
      alternative pathway-mediated C3 deposition and cytolysis but was less potent in
      circumventing classical pathway attack than cells that expressed DAF alone or DAF
      + MCP. Hybrid MCP-DAF may be useful for alleviating C-mediated cell damage,
      especially via the alternative pathway.

PMID- 7511648
TI  - Limited junctional diversity in kappa light chains. Junctional sequences from
      CD43+B220+ early B cell progenitors resemble those from peripheral B cells.
AB  - Among all adult T and B cell Ag receptor chains, only Ig light chains lack N
      regions. It is thought that this is due to the fact that light chain genes
      rearrange after heavy chain genes, and that terminal deoxynucleotidyl
      transferase, the enzyme that adds N regions, is not longer expressed at that
      stage. However, this concept has been challenged recently by the demonstration
      that 3 to 10% of B cell precursors (CD43+B220+) appear to rearrange their light
      chains at approximately the same time as they undergo VH-->DJ rearrangements. To
      examine N region addition in B cell precursors undergoing early kappa-chain
      rearrangement, we PCR amplified rearranged V kappa 21 genes from the CD43+B220+
      bone marrow cells and compared them to sequences obtained from whole bone marrow
      and spleen. Unexpectedly, all three populations showed approximately 10% N region
      containing junctions, most consisting of only one N nucleotide. Thus, even the B
      cell precursors that rearrange light chains at this early stage of development
      lack much N region diversity. Twelve percent of the sequences unambiguously
      contained P regions, which were from 1 to 5 nucleotides in length. All but 2 of
      the 41 productive rearrangements had the commonly observed CDR3 length of nine
      amino acids. Many (71%) of the sequences were out of frame. CDR3 length was very
      restricted in nonproductive rearrangements too, and deletion of nucleotides from
      V kappa and J kappa gene segments was limited. Thus, even at the level of
      nonproductive rearrangements, junctional diversity is minimal for kappa-chains.

PMID- 7511650
TI  - Inhibition of endothelial cell adhesion molecule expression with antisense
      oligonucleotides.
AB  - In response to inflammatory stimuli, expression of a group of proteins that bind
      circulating leukocytes (endothelial-leukocyte adhesion molecules) are induced on
      the luminal surface of vascular endothelium. A series of phosphorothioate
      oligonucleotides 18 to 21 bases in length were designed and synthesized to
      hybridize selectively to the mRNA, which encodes three such endothelial-leukocyte
      adhesion molecules; human intercellular adhesion molecule-1 (ICAM-1), vascular
      cell adhesion molecule-1 (VCAM-1), and E-selectin. Antisense oligonucleotides
      were identified that selectively inhibited ICAM-1, VCAM-1, and E-selectin
      expression in HUVEC. Oligonucleotides that hybridized to the 3'-untranslated
      region of either ICAM-1, VCAM-1, or E-selectin mRNAs promoted a selective
      reduction in the respective mRNA levels. In contrast, oligonucleotides that
      hybridized to 5'-untranslated sequences did not significantly reduce target mRNA
      levels, although they did promote a reduction in protein expression. With the use
      of flow cytometry to measure cell surface expression, ICAM-1 and E-selectin were
      selectively inhibited by their respective antisense oligonucleotide. At low
      concentrations of oligonucleotides, only VCAM-1 antisense oligonucleotides
      inhibited VCAM-1 expression. However, at an oligonucleotide concentration of 50
      nM or greater, phosphorothioate oligonucleotides not predicted to hybridize to
      VCAM-1 mRNA also reduced VCAM-1 expression. The sequence-independent inhibition
      of VCAM-1 expression by phosphorothioate oligonucleotides could be the result of
      a perturbation in the transcriptional regulation of the VCAM-1 gene. ICAM-1, VCAM
      1, and E-selectin antisense oligonucleotides reduced adhesion of HL-60 cells to
      TNF-activated HUVEC. These data demonstrate that phosphorothioate
      oligonucleotides are capable of selectively inhibiting the expression of ICAM-1,
      VCAM-1, and E-selectin in HUVEC.

PMID- 7511649
TI  - Members of the novel WC1 gene family are differentially expressed on subsets of
      bovine CD4-CD8- gamma delta T lymphocytes.
AB  - CD4-CD8- gamma delta T cells of ruminants uniquely express a 220-kDa surface Ag
      recognized by several mAbs clustered as WC1. We recently reported the isolation
      of a cDNA clone encoding a WC1 Ag. Southern blotting suggested that the bovine
      genome contains multiple sequences highly related to the isolated WC1 cDNA. Here,
      we demonstrate that some of the clustered WC1 mAbs stain predominantly
      nonoverlapping subsets of bovine CD4-CD8- gamma delta T cells. By the isolation
      of two additional cDNA clones encoding molecules highly related to the original
      WC1 Ag, we provide a molecular basis for this phenomenon. Cells transfected with
      cDNAs encoding individual WC1 Ags are differentially recognized by various WC1
      mAbs. Thus, expression of members of the WC1 gene family divides bovine CD4-CD8-
      gamma delta T cells into phenotypical subsets. Field inversion gel
      electrophoresis revealed that all WC1 genes map to a single, large (> 1 Mbp) Notl
      fragment. Although the function of WC1 remains unknown, it likely involves
      interaction with ligands that originate from a similarly complex genetic system.

PMID- 7511651
TI  - Histamine induces leukocyte rolling in post-capillary venules. A P-selectin
      mediated event.
AB  - The objective of this study was to systematically assess the molecular mechanisms
      and kinetics of histamine-induced leukocyte rolling in rat mesenteric venules
      using intravital microscopy. A complicating factor in these studies is surgical
      preparation-induced leukocyte rolling (spontaneous rolling), which leads to a
      lack of effect of histamine on this parameter. Therefore, we identified the
      source of the surgery-induced leukocyte rolling (partial mast cell degranulation)
      and established that pretreatment of animals with sodium cromoglycate (connective
      tissue mast cell stabilizer) inhibited spontaneous leukocyte rolling. Superfusion
      of the mast cell-stabilized rat mesentery with histamine caused a profound
      increase in leukocyte rolling which persisted for the entire hour of
      experimentation. Diphenhydramine (H1-receptor antagonist) but not cimetidine (H2
      receptor antagonist) prevented the rise in histamine-induced leukocyte rolling.
      An anti-P-selectin Ab but not an anti-CD18 Ab reversed the histamine-induced
      leukocyte rolling in a dose-dependent fashion. In this model of low base line
      rolling, exposure of the mesentery to the chemotactic agent platelet-activating
      factor did not induce leukocyte rolling or adhesion. However, co-administration
      of histamine with platelet-activating factor did indeed promote leukocyte
      adhesion suggesting that the presence of at least one effector of P-selectin is a
      minimal requirement for chemotactically-stimulated leukocytes to adhere to
      postcapillary venules. This study demonstrates for the first time that histamine
      induces leukocyte rolling via a P-selectin-dependent mechanism in vivo. This is a
      prolonged, H1 receptor-mediated event that may contribute significantly to the
      early phase of inflammation.

PMID- 7511652
TI  - Characterization of the E-selectin ligand on NK cells.
AB  - In this study we demonstrate that human CD56+CD16+/CD3- NK cells adhere to the E
      selectin expressed by stimulated HUVEC in a sialidase- and Ca(2+)-dependent
      manner, and express a silylated Lex adhesion structure. We have characterized
      this sLe(x) epitope on NK cell in detail and show here that the sLe(x) on NK
      cells was not recognized by the CSLEX1 Ab, but was readily identified by two anti
      di-sLe(x) Abs, KM-93 and FH-6. Furthermore, cleaving sialic acid with a sialidase
      treatment revealed a pool of Le(x) epitopes on the NK cells surface, providing
      further proof that NK cells express sLe(x) epitopes. Extensive protease
      treatments did not cleave the sLe(x) epitope from NK cells, which suggests that
      it could be linked to a lipid backbone. This di-sLe(x) was able to mediate
      adhesion to E-selectin, suggesting that it represents an essential part or is
      closely related to a selectin ligand on NK cells. We were also able to show that
      NK cells possess several alpha 2,3 sialyltransferases and alpha 1,3 or alpha
      1,3/4 fucosyltransferases. These enzymes are crucial in the synthesis of sLe(x)
      epitopes on cell surfaces. Taken together, we provide evidence that NK cells have
      a di-sLe(x) oligosaccharide capable of adhesion to E-selectin, and NK cells have
      the machinery (i.e., relevant transferases) to generate these sialylated Lewis
      oligosaccharides.

PMID- 7511653
TI  - Two proteolytic pathways for down-regulation of the barrier molecule CD43 of
      human neutrophils.
AB  - CD43, an anionic rod-like mucin molecule on white blood cells, is thought to
      provide a barrier that prevents interactions of other surface molecules and acts
      as negative regulator of cell function. As a correlate, CD43 is expected to be
      altered or down-regulated when blood cells are functionally activated. This study
      examines CD43 of blood neutrophils before and after treatment with known
      activating agents. Flow cytometry indicated that PMA and A23187, and to a much
      lesser extent, FMLP and IL-8, decrease neutrophil expression of CD43. Two
      separate mechanisms were identified for CD43 down-regulation. Both are
      proteolytic processes. PMA-induced down-regulation is a rapid process involving
      proteolysis at a minimum of two sites, one within the N-terminal distal region
      recognized by mAbs and the other at a membrane-proximal site. The PMA-induced
      protease, cd43' ase, is characterized by insensitivity to DFP, TLCK, leupeptin,
      pepstatin, and 1,10 phenanthroline (< 5 mM). PMA-induced CD43 down-regulation is
      extensive but never complete, terminating at approximately 10 min after down
      regulating 65 to 85% of molecules, and thereby converting neutrophils from dense
      to sparse CD43 expression. The second CD43 down-regulation mechanism, although
      likely a regulated event in vivo, occurred slowly in this study in neutrophils
      incubated without additives; the process is not affected by PMA, involves the
      action of a DFP-sensitive protease, releases N-terminal mAb-reactive fragments of
      52 kDa or 40 kDa and can be mimicked by exogenous neutrophil elastase. The
      complexity and apparent tight regulation described here for the two down
      regulatory mechanisms are consistent with an important role for CD43 in
      preventing or dampening cell surface interactions of blood neutrophils.

PMID- 7511654
TI  - An amino-terminal fragment of human lipopolysaccharide-binding protein retains
      lipid A binding but not CD14-stimulatory activity.
AB  - LPS-binding protein (LBP) mediates the pro-inflammatory effects of bacterial LPS
      by enhancing LPS-induced cytokine production by monocytic cells. LBP binds
      specifically to LPS to generate a complex that interacts with the CD14 receptor
      on the surface of responsive cells. To identify the biologically active regions
      of the protein responsible for mediating these activities, we cloned and
      expressed human rLBP (456 amino acids) as well as a truncated form encoding amino
      acids 1-197 (rLBP25). Both forms of LBP bound to LPS with the same affinity, and
      similarly inhibited LPS activity in the Limulus amebocyte lysate assay. These
      results demonstrate that the LPS-binding domain of LBP resides entirely within
      the N-terminal 197 amino acids of the protein. rLBP and rLBP25 were compared for
      their ability to mediate CD14-dependent LPS effects on cells. rLBP was effective
      in mediating uptake of LPS and stimulation of TNF production by human monocytic
      THP-1 cells, whereas rLBP25 had no significant activity in these assays.
      Similarly, rLBP was able to mediate LPS-induced TNF production by human PBMC
      whereas rLBP25 was essentially inactive. These results suggest that the
      structural features of LBP required for mediating LPS effects via CD14 are
      probably located in the C-terminal region of the protein. Thus, the LPS-binding
      activity of LBP can be separated from the CD14-stimulatory activity, suggesting
      these activities are mediated by structural elements residing in different
      regions of the protein.

PMID- 7511655
TI  - Autoantibody responses to the "native" 52-kDa SS-A/Ro protein in neonatal lupus
      syndromes, systemic lupus erythematosus, and Sjogren's syndrome.
AB  - Abs to the 52-kDa SS-A/Ro protein are found in high prevalence in patients with
      Sjogren's syndrome (SS) and mothers whose children have the neonatal lupus
      syndrome (NLS). This study further defines the specificity of this response. By
      ELISA, 97% of 59 mothers of offspring with NLS had Abs to the 52-kDa recombinant
      protein compared with 80% in 132 non-NLS sera with anti-SS-A/Ro Abs (p < 0.004).
      Antigenic regions on the 52-kDa protein were evaluated by immunoprecipitation of
      [35S]-radiolabeled in vitro translation products. Ninety-five percent of 99 sera
      that contained anti-52-kDa Abs by ELISA reacted with a large fragment spanning
      amino acids (aa) 1-291. Two antigenic regions were identified, aa169-291
      containing the leucine zipper that was recognized by 83% of the anti-52-kDa sera
      tested and aa1-78 containing the zinc finger domains that was recognized by only
      half the sera. No sera immunoprecipitated this N-terminal fragment exclusively.
      Recognition of one or both regions was not unique to any clinical subset of
      patients; however, a greater number of sera from patients with SS contained both
      specificities, whereas asymptomatic mothers whose children had NLS comprised the
      only clinical group in which the majority recognized the central region of the
      molecule. Reactivity with both epitopes was demonstrated significantly more often
      in sera with high titers of Abs to the 60-kDa rSS-A/Ro protein by ELISA in
      association with the anti-52-kDa response compared with anti-52-kDa responses
      associated with low titers of anti-60-kDa Abs (p < 0.04). Eighty-one percent of
      16 sera that recognized the N-terminal epitope were from patients with the
      combination of HLA-DRB1*0301, DQA1*0501, and DQB1*0201 alleles, compared with 30%
      of 10 that recognized only the central epitope (p < 0.02). In summary, this study
      demonstrates that there are at least two antigenic determinants on the 52-kDa SS
      A/Ro protein, one "immunodominant" and the other recognized by a more
      "restricted" subset of anti-52-kDa SS-A/Ro Abs.

PMID- 7511656
TI  - T cell determinant structure of myelin basic protein in B10.PL, SJL/J, and their
      F1S.
AB  - Recent experiments have shown that during the course of chronic experimental
      allergic encephalomyelitis, there is a shift in the determinant hierarchy away
      from the dominant to other subdominant and cryptic self determinants. It was
      therefore of interest to define the pattern of dominance for mouse myelin basic
      protein in the three commonly used experimental allergic encephalomyelitis model
      strains of mice, i.e., B10.PL, SJL/J, and (SJL x B10.PL)F1. Our studies indicate
      that many cryptic determinants are demonstrable, which only activate T cells on
      injection as individual peptides and not with the native protein. The core amino
      acid residues of the various determinants are defined and range in size between 5
      and 10 amino acids. Interestingly, there is a bias toward H-2u-restricted
      response vis-a-vis the H-2s-restricted response in the (SJL x B10.PL)F1 strain.
      The TCR V beta 8.2 gene segment was not predominantly used for responses to other
      determinants, although some B10.PL and (SJL x B10.PL)F1 cell lines expressed V
      beta 8.2 more than others. This study represents the most comprehensive analysis
      so far of the pattern of dominant and cryptic proliferative T cell determinants
      and their core sequences for mouse myelin basic protein.

PMID- 7511657
TI  - Specific down-regulation of proliferative T cell alloresponsiveness by
      interference with CD2/LFA-3 and LFA-1/ICAM-1 in vitro.
AB  - T cell activation requires Ag contact with the TCR in the presence of
      costimulatory signals provided by APCs. When Ag is presented without
      costimulation, T cells are functionally inactivated. Here we demonstrate that
      interference with distinct adhesion molecules during Ag contact using mAbs leads
      to Ag-specific functional inactivation of alloreactive T cells. We found that the
      presence of a mixture of mAbs specific for CD2, LFA-3, LFA-1 alpha- and beta
      chain, and ICAM-1 during primary MLC leads to down-regulation of secondary
      proliferative responses to Ag from the donor used for priming. Cells from
      pretreated cultures proliferated well, however, when stimulated with Ag from
      third party donors, mitogens, or mitogenic CD3 mAb. Because specific reactivity
      could be restored by addition of IL-2 to restimulation cultures, altered
      secondary responsiveness appeared to be caused by anergy and not by elimination
      of specific clones. Furthermore, specific down-regulation of alloresponsiveness
      was prevented by addition of IL-2 to primary cultures in the presence of mAb.
      Interference by mAb with either CD2/LFA-3, LFA-1/ICAM-1, CD2/LFA-1, or LFA-3/ICAM
      1 had a substantial, though less pronounced effect on secondary responsiveness.
      After pretreatment with the Ab mixture, CTL generation was substantially but
      incompletely down-regulated against the original and third party donors. Because
      a decrease in the reactivity of unstimulated responders by culture was also
      observed, these findings might be explained by the loss of cytotoxic precursors
      after culturing under nonstimulating conditions. In conclusion, our data
      demonstrate that T cells enter a state of anergy when T cell activation is
      modulated by simultaneous interference with distinct adhesion molecules during Ag
      contact, which thus might reflect at least partly overlapping functions of
      particular receptor-ligand pairs in T cell costimulation.

PMID- 7511658
TI  - Aged T cells are hyporesponsive to costimulation mediated by CD28.
AB  - The ability of T cells to proliferate in response to a number of stimuli is
      impaired in healthy, aged individuals. T cells from young (2 to 4 mo) and aged
      (20 to 26 mo) mice were stimulated with immobilized anti-CD3 epsilon-chain mAb
      and soluble anti-CD28 mAb. T cells from young and aged mice proliferated
      comparably in response to anti-CD3 epsilon mAb alone. However, aged T cells were
      significantly less responsive to costimulation by anti-CD28 mAb. This decreased
      response of aged T cells was seen at all dosages tested of anti-CD3 epsilon and
      anti-CD28 mAbs and in the presence and absence of APC. Similar results were
      observed when costimulation was provided by B7-transfected L cell fibroblasts. T
      cells from young and aged mice had comparable expression of CD28 by flow
      cytometry, both before and after stimulation. The defect in response to CD28 was
      seen both in CD4+ and CD8+ T cells and in CD44lo (naive) and CD44hi (memory) T
      cells. The impaired response to costimulation mediated by CD28 on T cells from
      aged mice may be an important factor in reduced T cell responses associated with
      aging.

PMID- 7511659
TI  - Adhesion through the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and the VLA-4 (CD49d)-VCAM
      1 (CD106) pathways prevents apoptosis of germinal center B cells.
AB  - In the germinal center (GC), B cells are either selected to become memory cells
      or are eliminated through the process of programmed cell death. FDC which are
      intimately associated with the GC B cells are thought to be important in this
      selection process. Previously, we have shown that the LFA-1 (CD11a/CD18)-ICAM-1
      (CD54) and VLA-4 (CD49d)-VCAM-1 (CD106) adhesion pathways are involved in FDC-B
      cell interaction. In the present study, we have explored whether these adhesive
      interactions contribute to the process of B cell selection by studying the
      effects on apoptosis of GC B cells. Using FDC and B cells derived from human
      tonsils, we found that only B cells adherent to FDC remain viable: disruption of
      FDC-B-cell clusters with mAb against LFA-1 alpha (CD11a), VLA-4 (CD49d), ICAM-1
      (CD54), or VCAM-1 (CD106) results in apoptosis of the B cells. Furthermore, we
      found that GC B cells, upon adhesion to plastic-coated purified ICAM-1 (CD54) or
      VCAM-1 (CD106), show diminished apoptosis. Importantly, we observed that, at low
      concentration, ICAM-1 (CD54) and VCAM-1 (CD106) act synergistically with anti
      IgM, in inhibiting apoptosis. Together, our data strongly suggest that adhesion
      of B cells via the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) pathway and VLA-4 (CD49d)
      VCAM-1 (CD106) pathway contributes to B cell selection.

PMID- 7511660
TI  - A positively selecting thymic epithelial cell line lacks costimulatory activity.
AB  - The participation of costimulatory molecule interactions in positive selection of
      T lymphocytes was addressed by assessing the ability of a positively selecting
      thymic epithelial cell (TEC) line, 427.1, to stimulate allospecific CTL
      responses. Stimulation of H-2s spleen cells with the H-2b expressing 427.1 line
      does not result in the generation of cells capable of lysing H-2b target cell
      lines. The level of expression of MHC class I molecules by 427.1 is lower than
      that found in other stimulatory TEC lines. However, this finding does not account
      for the nonstimulatory phenotype. Up-regulation of MHC class I did not result in
      stimulation, and fusion of 427.1 cells with stimulatory TEC resulted in a line
      with low MHC class I molecule expression and stimulatory phenotype. The TEC line
      427.1 does not express the costimulatory molecule B7/BB1, and transfection of the
      B7/BB1-encoding DNA results in expression of the molecule and conversion into a
      stimulatory phenotype, demonstrating directly that the non-stimulatory phenotype
      is a result of lack of costimulation. However, B7/BB1 expression does not improve
      the ability of 427.1 TECs to induce positive selection. Intrathymic injection of
      the B7/BB1 transfected, compared with mock transfected 427.1 cells, rescued fewer
      CD8+ mature thymocytes in beta 2-microglobulin negative mice. Therefore, unlike
      the peripheral T cell responses to Ag, positive selection of T cells in the
      thymus may not depend on the costimulation provided by the presenting cell.

PMID- 7511662
TI  - Use of global amino acid replacements to define the requirements for MHC binding
      and T cell recognition of moth cytochrome c (93-103).
AB  - Substitution with all naturally occurring L-amino acids at each of 11 residues of
      the IEk-restricted month cytochrome c (93-103) epitope has allowed us to analyze
      the requirements for MHC binding and T cell recognition to a level of definition
      not previously possible. Substitutions at only three positions systematically
      affect MHC binding and three others appear to be the major TCR contacts.
      Interestingly, changing residues involved in MHC binding can ablate T cell
      recognition without altering MHC association. Additionally, residue identity at
      two positions that do not appear critical for MHC binding, nor to be involved in
      specific T cell contact, nonetheless dramatically affect T cell responses. This
      suggests that peptides differing only slightly in sequence can have significantly
      altered conformations within the class II MHC binding groove. We have also
      developed a simple scoring program that uses the binding data to quantitate how
      well a given peptide fits the MCC motif. All strongly immunogenic IEk-restricted
      epitopes score highly (> or = 0.70, where 1.0 is perfect concordance), and only
      3% of all potential nonameric peptides in the two main protein sequence databases
      have scores greater than 0.70. This indicates that the global amino acid
      replacement approach using a single peptide is an efficient means of deriving
      binding motifs for a given class II MHC molecule, and should aid in the
      identification of novel T cell epitopes.

PMID- 7511661
TI  - Role of HLA-A motifs in identification of potential CTL epitopes in human
      papillomavirus type 16 E6 and E7 proteins.
AB  - We have measured the binding affinity for five HLA-A alleles: HLA-A1 (A*0101),
      A2.1 (A*0201), A3 (A*0301), A11 (A*1101), and A24 (A*2401); of a set of all
      possible nonamer peptides (n = 240) of human papillomavirus type 16 E6 and E7
      proteins. High affinity binding peptides were identified for each of the alleles,
      thus allowing us to select several candidates for CTL-based vaccines. Moreover,
      this unbiased set of peptides allowed an evaluation of the predictive value of
      HLA motifs derived either from the analysis of sequencing of pools of naturally
      processed peptides or from the binding analysis of polyalanine nonameric peptides
      that differed in the amino acids (aa) present at the anchor positions. Whereas
      pool sequencing-derived motifs were present in only 27% of high affinity binders,
      the more expanded motif, based on analysis of different aa substitutions at the
      anchor positions, was present in 73% of high affinity binders. Furthermore, it
      was found that the presence of anchor residues in a peptide was in itself not
      sufficient to determine binding to MHC class I molecules, because the majority of
      motif-containing peptides failed to bind to the relevant MHC. Finally, specific
      HLA motifs were used to predict peptide binders of 8, 10, and 11 aa in length.
      Several high affinity binding peptides were identified for each of the various
      peptide lengths, indicating a significant size heterogeneity in peptides capable
      of high affinity binding to HLA-A molecules.

PMID- 7511663
TI  - Ligand-induced adhesion to activated endothelium and to vascular cell adhesion
      molecule-1 in lymphocytes transfected with the N-formyl peptide receptor.
AB  - Binding of FMLP to the neutrophil N-formyl peptide receptor (FPR) transmits
      signals through pertussis toxin-sensitive G proteins triggering Ca2+ flux,
      superoxide production, granule exocytosis, and neutrophil aggregation and
      adhesion involving the beta 2 (CD18) integrins. Expression of the FPR in mouse
      fibroblasts or human kidney cells has been shown to confer an N-formyl peptide
      inducible Ca2+ flux in transfectants. Here we demonstrate that the transfected
      receptor can also support ligand-induced alterations in cellular adhesion. We
      established stable transfectants of mouse L1-2 pre-B cells with cDNA for human
      FPR (L1-2 FPR cells). The transfectants bind N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys
      fluorescein with 1.4 x 10(5) sites per cell and a dissociation constant of 3.3
      nM. Stimulation with FMLP induces a transient Ca2+ flux. FMLP also triggers
      adhesion of L1-2 FPR cells to TNF-alpha- or LPS-activated bEnd3 cells (mouse
      brain-derived endothelial cells) and to purified mouse VCAM-1. Binding is
      inhibited by Abs to VCAM-1 and to the alpha-chain of its lymphocyte receptor (the
      alpha 4 beta 1 integrin, VLA-4). Stimulation with FMLP does not induce a change
      in cell surface expression of alpha 4. Induced adhesion to VCAM-1 is rapid,
      detectable at the earliest times measurable (30 to 60 s after FMLP addition), and
      is inhibited by pertussis toxin. We conclude that FPR can mediate integrin
      activation not only in neutrophils but also in lymphocytes, and can trigger rapid
      adhesion via lymphocyte alpha 4 beta 1. The adhesion of lymphocytes is critical
      to their migration and targeting; our results suggest the possibility of
      manipulating adhesive responses through expression of chemoattractant receptors
      in lymphoid cells engineered for cellular therapy, allowing targeted adhesion and
      potentially migration in response to locally administered ligands.

PMID- 7511664
TI  - Induction of IL-3 and granulocyte-macrophage colony-stimulating factor by
      substance P in bone marrow cells is partially mediated through the release of IL
      1 and IL-6.
AB  - Experimental data strongly suggest that the nervous and immune systems are
      interrelated. One example of this interrelation is anatomical and is represented
      by innervation of the lymphoid organs by substance P (SP) immunoreactive fibers,
      among others. Neurotransmitters/neuropeptides can exert functional receptor
      mediated immunologic responses. SP binding to its receptor induces cytokine
      production in macrophages and T cells and stimulates IgG secretion from B cells.
      SP has also been associated with inflammation and other immune-mediated diseases
      such as arthritis. We have previously reported an in vitro stimulatory effect of
      SP on hematopoiesis that was mediated mostly by the induction of two relevant
      hematopoietic growth factors, IL-3 and granulocyte-macrophage-CSF (GM-CSF). In
      this study, we have shown that SP, through the carboxyl terminus, induces the
      production of IL-3 and GM-CSF in bone marrow mononuclear cells. This production
      requires de novo synthesis and is blocked by two different SP-R antagonists,
      spantide and CP-96,345-1. The induction of IL-3 and GM-CSF is partially mediated
      by IL-1 and IL-6, which are also produced by bone marrow mononuclear cells.
      Furthermore, the production of IL-3 and GM-CSF correlated with an accumulation of
      their respective steady state mRNAs. T cells found within the bone marrow are
      responsible for most of the induced IL-3. Because SP mediates the release of IL
      1, IL-3, IL-6, and GM-CSF, all important hematopoietic regulators, by bone marrow
      cells, this study further suggests the possibility of a regulatory role of the
      nervous system in hematopoiesis mediated by neuropeptides such as SP.

PMID- 7511666
TI  - Complement-inhibiting activities of human CD59 and analogues from rat, sheep, and
      pig are not homologously restricted.
AB  - Human erythrocyte CD59 and analogues isolated from erythrocytes of rat, sheep,
      and pig were examined for their ability to protect erythrocytes from various
      species against lysis by C from homologous and heterologous sources. In all
      cases, incorporation of human CD59 or analogues from rat, sheep, and pig
      efficiently protected guinea pig erythrocytes against lysis by C homologous with
      the CD59. However, each of the CD59 analogues also conferred on guinea pig
      erythrocytes protection against C from most heterologous species. These results
      demonstrate that none of the CD59 analogues tested were species specific in their
      C-inhibiting activity. Erythrocytes from species other than guinea pig could not
      be protected by incorporation of any of the available CD59 analogues despite
      similar incorporation in all erythrocytes tested. We suggest that the presence of
      endogenous inhibitors on these other erythrocytes masks the activity of
      incorporated CD59. Evidence that is supportive of this hypothesis was provided by
      demonstrating that blocking the endogenous CD59 with mAbs rendered erythrocytes
      susceptible to inhibition by high dosages of incorporated CD59.

PMID- 7511665
TI  - Induction, characterization, and functional coupling of the high affinity
      chemokine receptor for RANTES and macrophage inflammatory protein-1 alpha upon
      differentiation of an eosinophilic HL-60 cell line.
AB  - Eosinophilic differentiation of a pro-eosinophilic HL-60 cell line resulted in
      the induction of a high affinity RANTES/macrophage inflammatory protein-1 alpha
      receptor. The induced receptor is biochemically indistinguishable in RANTES
      equilibrium-binding studies from the monocytic receptor expressed on THP-1 cell
      membranes. Continued expression of the receptor requires the continuous presence
      of the inducing stimulus, and receptor site number declines without a loss of
      binding affinity with a t1/2 of 11.5 h on withdrawal of the inducing stimulus.
      The induced receptor is capable of three physiologic measures of receptor
      coupling, namely, ligand-induced Ca2+ fluxes, priming of the respiratory burst,
      and chemotaxis. Dose-dependent Ca2+ fluxes were elicited upon increasing
      concentrations of RANTES and MIP-1 alpha whereas no response was measured upon
      addition of MIP-1 beta or MCP-1. In addition, desensitization studies
      demonstrated that previous exposure to either RANTES or MIP-1 alpha almost
      completely inhibits a Ca2+ flux upon subsequent exposure to either ligand.
      Priming of the respiratory burst to PMA in differentiated cells by human rRANTES
      was more effective than priming by IL-5 or granulocyte-macrophage-CSF, whereas
      undifferentiated cells failed to secrete superoxide anion. In addition,
      differentiated cells underwent chemotaxis in response to RANTES. This provides
      the first evidence for the induction of a C-C chemokine receptor upon
      eosinophilic differentiation of a leukocyte cell line, and is in keeping with the
      demonstrated ability of human RANTES to induce the rapid formation of
      eosinophilic inflammatory sites.

PMID- 7511667
TI  - Inactivation of nitric oxide synthase after prolonged incubation of mouse
      macrophages with IFN-gamma and bacterial lipopolysaccharide.
AB  - Large amounts of nitric oxide (NO) are produced by the inducible isoform of NO
      synthase (iNOS) in many cell types once the iNOS gene is transcriptionally
      activated. In primary mouse peritoneal macrophages elicited by thioglycolate
      broth, expression of iNOS follows treatment with IFN-gamma and is synergistically
      increased by the addition of bacterial LPS. Expression of iNOS is suppressible at
      transcriptional and translational levels by certain cytokines and microbial
      products. The present study describes a novel form of inactivation of iNOS that
      is post-translational and nondegradative. Mouse peritoneal macrophages cultured
      in the presence of IFN-gamma alone or IFN-gamma plus LPS rapidly depleted the
      medium of L-arginine, a substrate for iNOS, and stopped producing NO. Repletion
      of L-arginine permitted cells treated with IFN-gamma alone to resume NO
      production for at least 5 days, leading to the release of more NO than
      macrophages were previously believed capable of generating. L-Arginine repletion
      also boosted NO production by macrophages cultured for up to 2 to 3 days in the
      presence of IFN-gamma plus LPS, but thereafter, iNOS was inactive in these cells
      whether or not L-arginine was repleted. Activity of iNOS could be restored by
      adding both L-arginine and fresh IFN-gamma with or without LPS, likely reflecting
      the synthesis of new enzyme. However, the inactivation of iNOS seen late in
      culture with a single application of IFN-gamma plus LPS could be attributed
      neither to loss of iNOS protein nor to its autoinactivation by NO. Thus, LPS, a
      co-inducer of iNOS, causes macrophages to inactivate iNOS about 3 days after the
      onset of its induction. The mechanism, which remains to be identified, is novel
      for iNOS, in that it decreases neither its amount nor its apparent molecular
      mass.

PMID- 7511668
TI  - Autoreactive epitope profiles of the proliferating cell nuclear antigen define
      two classes of autoantibodies.
AB  - The proliferating cell nuclear antigen (PCNA) is a conserved protein required for
      cellular DNA replication. PCNA was first recognized using serum from the
      autoimmune disease SLE. To analyze the regions on PCNA that confer autoantibody
      binding, we modified the cDNA encoding full-length PCNA to generate a series of
      amino terminal, carboxyl terminal and internally deleted constructs, which were
      transcribed and then translated in vitro using the wheat germ cell-free
      translation system. An immunoprecipitation assay was used to study the ability of
      these mutated forms of PCNA to bind anti-PCNA Abs from patients with SLE. Eight
      of the ten sera studied required a protein of nearly full length for binding:
      antigenicity was abrogated by removal of 39 amino acids from the amino terminus,
      by various internal deletions, or by the removal of 15 (but not 11) amino acids
      from the carboxyl terminus. The remaining two sera exhibited an Ab-binding
      specificity to the carboxyl-terminally truncated proteins similar to that of the
      majority of anti-PCNA sera, but their specificity was different in the amino
      terminus: these sera were able to recognize PCNA lacking over 40% of sequence in
      the amino terminus, but they did not bind proteins with short internal deletions
      in that region. Thus, these epitopes appear to be conformational and distinguish
      two classes of autoimmune sera.

PMID- 7511669
TI  - Maturational changes in CD4+ cell subsets and lymphokine production in BXSB mice.
AB  - CD4+ cells are thought to play a significant role in the development of lupus
      like disease in a variety of autoimmune disease-prone mouse strains. In one such
      strain, BXSB/MpJScR, male mice develop severe lupus-like symptoms early in life
      but females do not. In this study, splenic CD4+ cells from male and female BXSB
      mice were evaluated for age-related changes in: 1) membrane expression of CD4+
      cell subset markers (1, 2, and 4 mo) and activation Ags (4 mo) and 2) the
      capacity to proliferate and produce cytokines (4 mo) in response to polyclonal
      stimuli. CD4+ cells from females of all age groups and from younger males were
      predominantly CD44lo, CD45RBhi, MEL-14hi, and 3G11hi (phenotypes associated with
      naive T cells). In contrast, 4-mo-old males were predominantly CD44hi, CD45RBlo,
      MEL-14lo, and 3G11lo (phenotypes associated with activated/memory T cells).
      Furthermore, an increased constitutive expression of the activation Ags RL388, IL
      2R, and TfR was observed in CD4+ cells of 4-mo-old male BXSB mice in comparison
      with age-matched females. In 3-day cultures, purified CD4+ cells from 4-mo-old
      males proliferated significantly less than cells from age-matched females in
      response to plate-bound anti-CD3 epsilon (2C11i). The reduced proliferation was
      restored in large part by PMA and ionomycin. CD4+ cells from older males
      generally produced increased amounts of IFN-gamma and IL-4 and significantly less
      IL-2 than age-matched females in response to either stimulus (IL-2 mRNA was also
      decreased in response to 2C11i). Taken together, these studies suggest that
      profound phenotypic and functional changes occur with age in the CD4+ cells of
      male BXSB mice that are indicative of an activated state.

PMID- 7511670
TI  - Vascular endothelial growth factor. A cytokine modulating endothelial function in
      rheumatoid arthritis.
AB  - Angiogenesis is important in the proliferation of inflammatory synovial tissue.
      Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that is
      also angiogenic in vivo. We examined the potential role of VEGF in mediating
      chemotaxis and proliferation of endothelial cells in rheumatoid arthritis (RA)
      using samples of synovial tissue and synovial fluid from 55 arthritic patients.
      Synovial fluid VEGF by ELISA was higher in RA synovial fluids (386 +/- 122 ng/ml)
      (SE) compared with osteoarthritis (OA) synovial fluids (< 0.8 ng/ml) (p < 0.05)
      or synovial fluids from patients with other arthritides (6.6 +/- 2 ng/ml). In
      addition to its known mitogenic properties, we found that human rVEGF was
      chemotactic for HUVECs at concentrations above 0.02 nM. Incubation of RA synovial
      fluids with neutralizing anti-VEGF resulted in 23 to 66% (mean 53 +/- 4%)
      inhibition of HUVEC chemotaxis. Conditioned medium from four of five RA synovial
      tissue explants was mitogenic for bovine adrenal capillary endothelial cells.
      Anti-VEGF neutralized from 19 to 42% (mean 28 +/- 4%) of this mitogenic activity.
      To determine the cellular source of VEGF in synovial tissue, we employed
      immunohistochemistry. VEGF+ cells were rarely (< 1%+) found in normal synovial
      tissues. In contrast, RA and OA synovial tissues exhibited VEGF+ lining cells (8%
      and 13%, respectively). A few synovial tissue macrophages were VEGF+ in both RA
      and OA (5% and 2%, respectively). These results elucidate a newly described
      function for VEGF as a potent chemotaxin for endothelial cells as well as a role
      for VEGF in RA-associated endothelial migration and proliferation.

PMID- 7511671
TI  - Human acetylcholine receptor presentation in myasthenia gravis. DR restriction of
      autoimmune T epitopes and binding of synthetic receptor sequences to DR
      molecules.
AB  - Autoimmune Th cells in myasthenia gravis recognize several sequence regions of
      the human muscle acetylcholine receptor (AChR). Most AChR Th epitopes are
      presented by HLA class II DR molecules (DR). Four sequence regions of the AChR
      alpha-subunit form Th epitopes recognized by most myasthenic patients,
      irrespective of their DR haplotype. In this study we first identified in five
      myasthenic patients the DR molecule(s) likely to be involved in presentation of T
      immunodominant AChR sequences. We then investigated the binding to the affinity
      purified DR molecules thus identified (DR2/w51, DR4/w53, and DR7/w53) and to the
      DR1 molecule, of a panel of overlapping synthetic peptides screening the human
      alpha-subunit sequence, previously used to identify AChR Th epitopes in
      myasthenic patients. The AChR peptides that stimulated anti-AChR autoimmune Th
      cells all bound the relevant DR molecules. Some AChR peptides never recognized by
      Th cells of myasthenic patients also bound well to one or more DR molecules. The
      relative ability to bind to DR molecules of different sequence regions of the
      AChR, i.e., an autoantigen, agrees well with the results of previous studies on
      the DR binding of synthetic sequences of exogenous antigens. Some peptide
      sequences uniquely bound one DR molecule, others bound several DR molecules, and
      others did not bind any of the DR molecules tested.

PMID- 7511672
TI  - 60-kDa Ro protein autoepitopes identified using recombinant polypeptides.
AB  - The human Ro ribonucleoprotein is a clinically important yet poorly understood
      autoantigen. The contribution of Ro autoantibodies to pathogenesis of autoimmune
      disease remains unclear, as do the stimuli that initiate and maintain the
      response. Recent evidence suggests that patient anti-Ro responses target
      individual proteins, including a 60- and a 52-kDa species, within the complex in
      a disease-specific manner. However, Ro antisera retain considerable heterogeneity
      in their recognition of both continuous and discontinuous epitopes on the protein
      components. Previous characterization of Ro autoepitopes has primarily involved
      solid phase assays, which are of limited value in identifying discontinuous
      epitopes. To address the heterogeneity of Ro and the issue of discontinuous
      autoepitopes, we have generated 10 overlapping recombinant polypeptides of the
      human 60-kDa Ro protein and compared their reactivities using a soluble
      immunoprecipitation assay. Seven different epitopes, both continuous and
      discontinuous, were distinguished and seven distinct patterns of reactivity were
      discerned among the sera from 12 patients. These patterns of reactivity showed no
      relationship to clinical diagnosis but did correlate with the titer of Abs
      against recombinant 60-kDa Ro and with the concomitant presence of Abs directed
      against recombinant 52-kDa Ro protein. Sera that immunoprecipitated only the full
      length 60-kDa protein had low or undetectable anti-60 kDa titers by ELISA and
      immunoblot using recombinant Ag, demonstrating a predominant recognition of
      discontinuous epitopes. These data indicate that autoantibody responses to the 60
      kDa Ro Ag can preferentially target discontinuous epitopes and that the ability
      to recognize continuous epitopes is accompanied by the appearance of 52-kDa Ro
      autoantibodies.

PMID- 7511673
TI  - Inhibition of experimental autoimmune encephalomyelitis by MHC class II binding
      competitor peptides depends on the relative MHC binding affinity of the disease
      inducing peptide.
AB  - Blocking of the Ag presentation function of MHC molecules by competitor peptides
      has been proposed as a potential immunotherapy for MHC-associated autoimmune
      diseases. Despite the fact that successful inhibition of experimental autoimmune
      encephalomyelitis (EAE) by coimmunization with competitor peptides had been
      achieved, it remained questionable whether the in vivo activity of such peptides
      was solely the result of MHC blockade. In the peptide MBP72-85-induced EAE model
      in Lewis rats, we designed a single amino acid-substituted analogue of MBP72-85
      with a superior MHC binding capacity, and with the capacity to activate
      encephalitogenic MBP72-85-specific T cells. Subsequently, two well-defined
      competitor peptides, one EAE related and one non-EAE related, were studied for
      their respective efficacies to inhibit the in vitro proliferation of an
      encephalitogenic T cell clone induced by the original MBP72-85 or the superior
      MHC binding analogue peptide. It appeared that the response to MBP72-85 was
      inhibited very efficiently by both competitor peptides, whereas the response to
      the superior MHC binding analogue peptide was not. Co-immunization of either the
      related or non-related competitor peptide together with MBP72-85 inhibited EAE
      induction in a concentration-dependent manner. In such protected rats, polyclonal
      T cell responses against MBP72-85 were dramatically decreased. However, EAE
      induced by the stronger MHC binding MBP72-85 analogue could not be inhibited by
      either of the competitor peptides. Moreover, in these rats, T cell priming for
      both MBP72-85 and the MBP72-85 analogue was not inhibited. These results show
      that competition for MHC binding in vivo could lead to inhibition of EAE
      induction.

PMID- 7511675
TI  - Structure and function of decay accelerating factor CD55.
AB  - Studies of decay-accelerating factor (DAF) function and structure are reviewed.
      DAF was first recognized as a species restricting factor operating at the level
      of C3/C5 activation. Cloning of the gene indicates that DAF has four short
      consensus repeats of the type characteristic of the regulators of complement
      activation gene cluster family. The third short consensus repeat is responsible
      for DAF's complement regulatory activity and signaling. DAF, like other
      glycophosphatidylinositol (GPI) anchored proteins, is associated with tyrosine
      kinases, and these kinases are probably the signaling devices. The details of how
      DAF's GPI anchor in the outer leaflet of plasma membrane connects with the
      tyrosine kinases on the inner leaflet are not known. Although DAF does not have
      an essential role in controlling hemolysis of erythrocytes, it does have
      important role in regulating the deposition of C3 on nucleated cells. The
      therapeutic potential of DAF is discussed.

PMID- 7511674
TI  - Interaction of hyperthermia and chemotherapy agents; cell lethality and oncogenic
      potential.
AB  - Hyperthermia was combined with bleomycin, melphalan and cis-platinum in order to
      examine cell lethality and oncogenic transformation in C3H10T1/2 cells from the
      adjuvant use of heat with chemotherapy agents. When cells were exposed
      concurrently to 42.5 degrees C and each of the three chemotherapy agents, heat
      enhanced both the cytotoxic and oncogenic potential of the drugs. Hyperthermia
      enhanced ratios were largest for bleomycin-treated cells. Examination of
      transformation incidences expressed as a function of surviving fraction, i.e. the
      cytotoxicity of treatment and therefore drug-heat efficacy, showed that for a
      given level of cell killing the combination of heat and cis-platinum resulted in
      fewer transformants per surviving cell than for cis-platinum alone. Hyperthermia
      appears to reduce the oncogenic potential of low concentrations of melphalan but
      has no effect on bleomycin-induced oncogenic transformation.

PMID- 7511676
TI  - Hydroxyethyl starch deferoxamine, a novel iron chelator, delays diabetes in BB
      rats.
AB  - Hydroxyl radicals (.OH) may contribute to beta cell death. Because iron catalyzes
      .OH production, we examined whether administration of a novel, long-acting iron
      chelator, hydroxyethyl starch-deferoxamine (HES-DFO) could prevent diabetes in
      spontaneously diabetic biobreeding (BB) rats. In our colony, a peripheral
      lymphocyte count (PBLC) < 4200 mm3 has an 88% positive predictive value for onset
      of diabetes mellitus (DM). Rats with PBLC < 4200 mm3 were randomized at 6 weeks
      of age to receive 50 mg/kg of HES-DFO (a high molecular weight hydroxyethyl
      starch-conjugated derivative of deferoxamine) or equimolar hydroxyethyl starch
      (HES) alone given intraperitoneally three times weekly until DM or 120 days of
      age. Administration of HES significantly decreased the incidence of IDDM to 57%
      as compared with the incidence of 87% in the lymphopenic unmanipulated BB rats in
      the colony (p < 0.01). Administration of HES-DFO further significantly decreased
      the incidence of IDDM to 31% as compared with the lymphopenic unmanipulated rats
      (p < 0.01). When analyzed by sex, 3 of 17 (18%) HES-DFO-treated males developed
      DM, versus 10 of 17 (58%) of HES-treated males (p < 0.05, chi square); 8 of 19
      (42%) of HES-DFO-treated females developed DM, versus 11 of 20 (55%) HES-treated
      females (p = NS). There were no differences between the groups in (1) mean time
      of onset of DM, (2) serum iron levels at study entry and completion, (3) weekly
      hematocrits, (4) total lymphocyte counts; and (5) weekly weight gains.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7511677
TI  - Priming of human monocyte superoxide production and arachidonic acid metabolism
      by adherence to collagen- and basement membrane-coated surfaces.
AB  - Monocytes (m phi s) come into intimate contact with basement membranes and
      extracellular matrix proteins as they extravasate from the blood to the
      interstitium or to sites of tissue injury. We examined the in vitro effects of m
      phi adherence to an endothelial cell-derived basement membrane or to purified
      extracellular matrix proteins on phorbol myristate acetate (PMA)-stimulated
      superoxide production and prostanoid secretion. Elutriation-purified human
      peripheral blood m phi s were adhered to tissue culture wells that were precoated
      with the following purified proteins: bovine serum albumin (BSA), collagen type I
      (COL I), collagen type IV (COL IV), fibronectin (FN), or laminin (LM). To model
      the provisional matrix at sites of tissue injury, m phi s were also adhered to
      wells coated with either denatured collagen type I or gelatin (GEL) or coated
      with basement membrane (BM) derived from endothelial cell monolayers. The m phi s
      were adhered to the protein-coated surfaces for 1 h at 37 degrees C in serum-free
      medium and washed to remove nonadherent cells, and the number of adherent m phi s
      was measured. Monolayers of m phi s were also incubated for an additional 18 h,
      at which time both adherence and cell spreading were measured. PMA-stimulated
      superoxide production by adherent m phi s was determined after 1 and 18 h of
      adherence to the protein-coated surfaces. PMA-stimulated release of two
      prostanoids, prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) was measured after
      18 h of m phi adherence to the surfaces. Following 18 h of adherence, PMA
      stimulated superoxide anion secretion and secretion of PGE2 and TxB2 were
      augmented of primed by m phi s adherent to COL I, GEL, or BM. In contrast, no
      such priming effects were observed by m phi s adherent to COL IV, FN, or LM. The
      results suggest that adherence to basement membranes, collagen type I-containing
      surfaces in the interstitium, or denatured collagen at sites of tissue injury
      primes m phi respiratory burst and arachidonate metabolism to inflammatory
      agonists. Induction of priming events by substrate-specific adherence may be an
      important factor regulating host defense functions of m phi s in the
      extracellular matrix.

PMID- 7511678
TI  - Serum components enhance bacterial lipopolysaccharide-induced tissue factor
      expression and tumor necrosis factor-alpha secretion by bovine alveolar
      macrophages in vitro.
AB  - We have compared the effect of bacterial lipopolysaccharide (LPS) in combination
      with normal adult bovine serum (NBS), fetal bovine serum (FBS), or a bovine serum
      fraction on tissue factor expression and tumor necrosis factor alpha (TNF-alpha)
      secretion by bovine alveolar macrophages. At a concentration of 1 ng/ml,
      bacterial LPS alone failed to induce measurable tissue factor expression by the
      macrophages, but the presence of FBS, NBS, or a fraction of normal pooled bovine
      serum isolated by ion-exchange chromatography (fraction 2) markedly potentiated
      the effect of LPS. A protein concentration of 64 micrograms/ml NBS, 192
      micrograms/ml FBS, and only 640 ng/ml fraction 2 was required to induce maximal
      tissue factor expression on the macrophages in combination with 1 ng/ml LPS.
      Comparison of quantities of added serum protein required to induce maximal
      potentiating effects indicated that fraction 2 was 100 times more potent than
      whole NBS and 300 times more potent than whole FBS. We similarly found that TNF
      alpha secretion by macrophages exposed to LPS was responsive to serum and was
      highly responsive to fraction 2. LPS alone (1 ng/ml) induced a relatively low
      level of TNF-alpha secretion by the macrophages, and the presence of FBS, NBS, or
      fraction 2 potentiated the effect of LPS. A concentration of 64.0 micrograms/ml
      NBS, 320.0 micrograms/ml FBS, and 3.2 micrograms/ml fraction 2 serum protein
      induced near-maximal TNF-alpha secretion by the macrophages. Comparison of the
      concentration of serum protein required to induce these potentiating effects
      indicated that fraction 2 was approximately 20 times more potent than whole NBS
      and 100 times more potent than whole FBS. The stimulatory effect of LPS plus
      fraction 2 serum proteins was dependent on the CD14 receptor, as monoclonal
      antibodies directed against CD14 (My4, 60bd; 10 micrograms/ml) inhibited tissue
      factor expression and TNF-alpha secretion by the macrophages.

PMID- 7511680
TI  - Induction of nitric oxide release by MRC OX-44 (anti-CD53) through a protein
      kinase C-dependent pathway in rat macrophages.
AB  - Many membrane proteins are implicated in the control of cell function by
      triggering specific signaling pathways. There is a new family of membrane
      proteins, defined by its structural motifs, which includes several lymphoid
      antigens, but lacks a function. To study its biological role, we determined which
      signaling pathways are affected by the CD53 antigen, a prototypic member of this
      family, in rat macrophages. Activation of CD53 by cross-linking results in an
      increase in inositol phosphates and diacylglycerol and in Ca2+ mobilization,
      which are insensitive to pertussis or cholera toxins. There is a translocation of
      protein kinase C to the membrane accompanied by nitric oxide (NO) release in
      macrophages. This effect is the result of the expression of the inducible nitric
      oxide synthase (iNOS), which is dependent on protein kinase C and protein
      synthesis. These results have linked a new receptor with a specific pathway of NO
      induction and thus have opened up a novel aspect of NO regulation in cell
      biology.

PMID- 7511682
TI  - An alloresponse in humans is dominated by cytotoxic T lymphocytes (CTL) cross
      reactive with a single Epstein-Barr virus CTL epitope: implications for graft
      versus-host disease.
AB  - The phenomenon of T cell allorecognition is difficult to accommodate within the
      framework of a T cell repertoire positively selected in the thymus, unless
      allorecognition results from the cross-reactions of self-major histocompatibility
      complex restricted T cells. Herein, we demonstrate the dual specificity of
      cytotoxic T lymphocyte (CTL) clones for the immunodominant Epstein-Barr virus
      (EBV) epitope FLRGRAYGL, presented on HLA-B8, and the alloantigen HLA-B*4402. CTL
      which recognized peptide FLRGRAYGL in association with HLA-B8 could be
      reactivated in vitro from healthy individuals who had been exposed previously to
      EBV, using stimulator cells expressing the cross-reacting alloantigen HLA-B*4402.
      Limiting dilution analysis of the alloresponse to HLA-B*4402 in eight healthy
      individuals revealed that HLA-B8+, EBV-sero+ donors had higher CTL precursor
      frequencies for alloantigen HLA-B*4402 than EBV-sero- control donors. It is
      surprising that the majority (65-100%) of anti-HLA-B*4402 CTL, generated in
      limiting dilution mixed lymphocyte reactions between responder cells from HLA
      B8+, EBV-sero+ individuals and HLA-B*4402+ stimulators, also recognized the EBV
      CTL epitope FLRGRAYGL/HLA-B8. In contrast to previous studies showing extensive
      diversity in the T cell repertoire against individual alloantigens, these data
      demonstrate that the response to an alloantigen can be dominated by CTL cross
      reactive with a single viral epitope, thus illustrating a possible mechanism for
      the frequent clinical association between herpesvirus exposure and graft-versus
      host disease after bone marrow transplants.

PMID- 7511679
TI  - The B cell-specific transcription factor BSAP regulates B cell proliferation.
AB  - The B cell-specific activator protein (BSAP) is a DNA-binding transcription
      factor expressed in pro-B, pre-B, and mature B cells, but not in plasma cells. In
      this study, we explored the role of BSAP in B cell function by assessing how the
      content of this protein varies in cells driven by proliferative stimuli and,
      conversely, how artificial manipulation of BSAP activity affects cell
      proliferation. We found that BSAP activity of nuclear extracts increased when B
      cells were activated by mitogen (lipopolysaccharide [LPS]), antigen receptor
      mediated signaling (surface immunoglobulin D [IgD] cross-linking) or T cell
      dependent stimulation (CD40 cross-linking). We could suppress BSAP activity by
      exposure of B cells to phosphorothioate oligonucleotides antisense to the BSAP
      translation initiation start site, whereas control oligonucleotides were
      virtually inactive. Antisense-induced BSAP suppression was associated with a
      striking reduction in LPS-induced proliferation of splenic B cells and in the
      spontaneous proliferation of B lymphoma cells (CH12.LX), but the antisense
      oligonucleotide had virtually no effect on proliferation of two cell lines
      lacking BSAP: the T lymphoma line EL-4 and the plasma cell line MOPC-315.
      Overexpression of BSAP in splenic B cells or de novo expression in MOPC-315
      plasma cells induced by transfection of a BSAP expression plasmid stimulated cell
      proliferation. Taken together, these results suggest that BSAP activity is a rate
      limiting regulator of B cell proliferation. We also found that treatment with the
      antisense BSAP oligonucleotide downregulated Ig class switching induced by
      interleukin 4 plus LPS. This effect may be secondary to reduced proliferation or
      could be mediated through BSAP binding sites in the IgH locus.

PMID- 7511681
TI  - Role of vascular cell adhesion molecule 1/very late activation antigen 4 and
      intercellular adhesion molecule 1/lymphocyte function-associated antigen 1
      interactions in antigen-induced eosinophil and T cell recruitment into the
      tissue.
AB  - To determine the role of vascular cell adhesion molecule 1 (VCAM-1)/very late
      activation antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM
      1)/lymphocyte function-associated antigen 1 (LFA-1) interactions in causing
      antigen-induced eosinophil and T cell recruitment into the tissue, we studied the
      effect of the in vivo blocking of VCAM-1, ICAM-1, VLA-4, and LFA-1 by
      pretreatment with monoclonal antibodies (mAb) to these four adhesion molecules on
      the eosinophil and T cell infiltration of the trachea induced by antigen
      inhalation in mice. The in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1
      and LFA-1, prevented antigen-induced eosinophil infiltration into the mouse
      trachea. On the contrary, the in vivo blocking of VCAM-1 and VLA-4, but not of
      ICAM-1 and LFA-1, increased blood eosinophil counts after antigen challenge, but
      did not affect blood eosinophil counts without antigen challenge in sensitized
      mice. Furthermore, the expression of VCAM-1 but not ICAM-1 was strongly induced
      on the endothelium of the trachea after antigen challenge. In addition,
      pretreatment with anti-IL-4 mAb decreased the antigen-induced VCAM-1 expression
      only by 27% and had no significant effect on antigen-induced eosinophil
      infiltration into the trachea. The in vivo blocking of VCAM-1 and VLA-4 inhibited
      antigen-induced CD4+ and CD8+ T cell infiltration into the trachea more potently
      than that of ICAM-1 and LFA-1. In contrast, regardless of antigen challenge, the
      in vivo blocking of LFA-1, but not of ICAM-1, increased blood lymphocyte counts
      more than that of VCAM-1 and VLA-4. These results indicate that VCAM-1/VLA-4
      interaction plays a predominant role in controlling antigen-induced eosinophil
      and T cell recruitment into the tissue and that the induction of VCAM-1
      expression on the endothelium at the site of allergic inflammation regulates this
      eosinophil and T cell recruitment.

PMID- 7511683
TI  - T cell costimulation by B7/BB1 induces CD8 T cell-dependent tumor rejection: an
      important role of B7/BB1 in the induction, recruitment, and effector function of
      antitumor T cells.
AB  - A successful antitumor T cell immune response involves induction, recruitment,
      and effector function of T cells. While B7/BB1 is known as a major costimulatory
      molecule in the induction of T cell responses, its role in T cell recruitment and
      effector function is still unclear. In this study, we show that introducing a
      major costimulatory molecule B7/BB1 into a major histocompatibility complex class
      II-negative tumor cell line, J558, results in a drastic reduction of its
      tumorigenicity. The tumor rejection depends on CD8 T cells but not CD4 T cells.
      However, unlike the previous reports on melanoma cell lines, B7/BB1-transfected
      J558 cells fail to induce cross-protection against parental J558 cells. The
      B7/BB1-transfected (J558-B7), but not untransfected J558 cells (J558-Neo) induce
      a CD8 T cell-dominant inflammatory response, and the T cells isolated from the
      tumor infiltrating lymphocytes (TIL) are polyclonal in terms of their T cell
      receptor V beta usage. Most surprisingly, the freshly prepared TIL have a potent,
      CD8 T cell-mediated cytotoxicity on tumor cells without any in vitro stimulation.
      The cytotoxic T lymphocyte (CTL) activity can be blocked by anti-CD8 monoclonal
      antibody (mAb). Interestingly, the CTL lyse J558-B7 about 10- to 80-fold more
      efficiently than untransfected J558-Neo cells. This preferential lysis cannot be
      attributed to recognition of B7/BB1-derived antigen by the T cells. This finding,
      together with the lack of the cross-protection between the J558-B7 and J558-Neo,
      suggests that B7/BB1 can also function at the effector phase of CTL responses.
      This notion is confirmed by our findings that the lysis of J558-B7 can be blocked
      by anti-B7 mAbs. Taken together, our results indicate that not only can the
      B7/BB1 molecule function as a costimulatory molecule at the initiation of immune
      response, it can also play a major role in T cell recruitment and effector
      function. This conclusion has significant implications for immunotherapy of
      tumors.

PMID- 7511684
TI  - T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in
      Epstein-Barr virus isolates from highly A11-positive populations by selective
      mutation of anchor residues.
AB  - Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus of humans that elicits
      strong HLA class I-restricted cytotoxic T lymphocyte (CTL) responses. An
      influence of such responses on virus evolution was first suggested by our finding
      that EBV isolates from the highly HLA A11-positive Papua New Guinea (PNG)
      population carried a lys-thr mutation at residue 424 of the nuclear antigen EBV
      encoded nuclear antigen (EBNA4) that destroyed the immunodominant target epitope
      for A11-restricted CTL recognition. Here we turn to a much larger population,
      Southern Chinese, where the A11 allele is again present in over 50% of the
      individuals. Each of 23 EBV isolates analyzed from this population were also
      mutated in the EBNA4 416-424 epitope, the mutations selectively involving one of
      the two anchor residues in positions 2 (417 val-leu) or 9 (424 lys-asp, -arg or 
      thr) that are critical for A11-peptide interaction. The majority of the Chinese
      isolates and all 10 PNG isolates also carried mutations affecting positions 1 and
      2 of the next most immunodominant A11-restricted epitope, EBNA4 residues 399-408.
      These changes clearly affected antigenicity since A11-positive lymphoblastoid
      cell lines (LCLs) carrying these mutant EBV strains were not recognized by A11
      restricted CTLs raised against the prototype B95.8 virus. Furthermore, Chinese
      donors naturally infected with these mutant viruses did not mount detectable A11
      restricted CTL responses on in vitro stimulation with autologous LCL cells
      carrying either the B95.8 or their endogenous EBV strain. In two different highly
      A11-positive populations, therefore, immune pressure appears to have selected for
      resident EBV strains lacking immunodominant A11-restricted CTL epitopes.

PMID- 7511685
TI  - Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two
      mechanisms with divergent biological consequences.
AB  - We show that the adhesion of T lymphoid cells to immobilized fibronectin can be
      increased by two distinct mechanisms. The first is by increasing the affinity of
      the fibronectin receptor/ligand interaction using the anti-beta 1 integrin
      monoclonal antibody 8A2. The second is by treating the cells with phorbol 12
      myristate 13-acetate (PMA), which alters events that occur after receptor
      occupancy (e.g., cell spreading) without affecting receptor affinity. The effects
      of these two mechanisms on adhesion in the presence of physiological
      concentrations of soluble fibronectin suggest that they have different biological
      consequences. Under these conditions, the net effect of increasing the affinity
      of the fibronectin receptors is to decrease cell adhesion, whereas the increase
      in adhesion induced by PMA is unaffected. This suggests that the high affinity
      receptors are not primarily available for cell adhesion under these
      circumstances, and that they have an alternative function. We further show that
      high affinity binding of soluble fibronectin can be induced by either
      differentiation of the monocytic cell line THP-1 or by cross-linking the T cell
      receptor complexes on the T lymphoid cell line HUT-78. The differentiated
      monocytic cells express two populations of fibronectin receptors: a minority in a
      high affinity state, and the majority in a low affinity state. Thus they will
      both continue to adhere in the presence of physiological concentrations of
      soluble fibronectin and bind significant amounts of soluble fibronectin at the
      cell surface.

PMID- 7511686
TI  - Autoantigens targeted in systemic lupus erythematosus are clustered in two
      populations of surface structures on apoptotic keratinocytes.
AB  - Systemic lupus erythematosus is a multisystem autoimmune disease in which the
      autoantibody response targets a variety of autoantigens of diverse subcellular
      location. We show here that these autoantigens are clustered in two distinct
      populations of blebs at the surface of apoptotic cells. The population of smaller
      blebs contains fragmented endoplasmic reticulum (ER) and ribosomes, as well as
      the ribonucleoprotein, Ro. The larger blebs (apoptotic bodies) contain
      nucleosomal DNA, Ro, La, and the small nuclear ribonucleoproteins. These
      autoantigen clusters have in common their proximity to the ER and nuclear
      membranes, sites of increased generation of reactive oxygen species in apoptotic
      cells. Oxidative modification at these sites may be a mechanism that unites this
      diverse group of molecules together as autoantigens.

PMID- 7511689
TI  - Inositol-trisphosphate-dependent calcium currents precede cation currents in
      insect olfactory receptor neurons in vitro.
AB  - Specialized olfactory receptor neurons in insects respond to species-specific sex
      pheromones with transient rises in inositol trisphosphate and by opening
      pheromone-dependent cation channels. These channels resemble cation channels
      which are directly or indirectly Ca(2+)-dependent. But there appear to be no
      internal Ca2+ stores in the outer dendrite where the olfactory transduction
      cascade is thought to start. Hence, it remains to be determined whether an influx
      of external Ca2+ precedes pheromone-dependent cation currents. Patch clamp
      measurements in cultured olfactory receptor neurons from Manduca sexta reveal
      that a transient inward current precedes pheromone-dependent cation currents. A
      transient inositol trisphosphate-dependent Ca2+ current, also preceding cation
      currents with the characteristics of pheromone-dependent cation currents, shares
      properties with the transient pheromone-dependent current. These results match
      the biochemical measurements with the electrophysiological data obtained in
      insect olfactory receptor neurons.

PMID- 7511687
TI  - Changes in sodium and calcium channel activity following axotomy of B-cells in
      bullfrog sympathetic ganglion.
AB  - 1. Currents mediated by Ca2+ channels using Ba2+ as a charge carrier (IBa), Na+
      currents (INa) and voltage- and Ca(2+)-dependent K+ currents (IC) were recorded
      from bullfrog paravertebral sympathetic ganglion B-cells using whole-cell patch
      clamp recording techniques. Currents recorded from control cells were compared
      with those from axotomized cells 13-15 days after transection of the
      postganglionic nerve. 2. Axotomy reduced peak IBa at -10 mV (holding potential = 
      80 mV) from 3.3 +/- 0.3 nA (n = 42) to 1.7 +/- 0.1 nA (n = 39, P < 0.001). Tail
      IBa at -40 mV following a step to +70 mV from a holding potential of -80 mV was
      also reduced in axotomized neurones (9.7 +/- 0.6 nA for forty-two control
      neurones and 5.2 +/- 0.3 nA for thirty-nine axotomized neurones; P < 0.001).
      Minimal changes were observed in the kinetics of activation and deactivation. 3.
      Pharmacological experiments using 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-
      trifluoromethylphenyl)-pyridine-5-carboxylic acid methyl ester (BayK 8644),
      nifedipine and omega-conotoxin showed that axotomy predominantly affected the N
      type Ca2+ channels which carry the majority of ICa in these neurones. L-type Ca2+
      current was little affected and T-type Ca2+ currents were not observed in control
      or axotomized cells. 4. Development of inactivation of 0 mV and recovery from
      inactivation of IBa at -80 mV exhibited three distinct components in both control
      and axotomized neurones: 'fast', 'intermediate' and 'slow'. The relative
      proportions of both the 'fast' and 'intermediate' components of inactivation at 0
      mV were almost doubled after axotomy (fast component was 15% in control and 29%
      in axotomized neurones; intermediate component was 17% in control and 26% in
      axotomized neurones). 'Fast' and 'intermediate' inactivation tended to develop
      more rapidly and recover more slowly after axotomy. The rate of onset of 'slow'
      inactivation was unaffected by axotomy but the steady-state level at -40 mV was
      increased. Most of the change in IBa properties may be secondary to enhanced
      inactivation associated with axotomy. 5. Axotomy reduced IC (measured at the end
      of a 3 ms step from -40 to +20 mV) from 34.5 +/- 4.9 (n = 26) to 19.2 +/- 1.5 nA
      (n = 49, P < 0.005). This reduction may be secondary to the reduction in calcium
      channels available for activation from -40 mV following axotomy. 6. The TTX
      sensitive and TTX-insensitive components of peak Na+ conductance (GNa) were both
      increased after axotomy. Total GNa was increased from 184.9 +/- 8.4 to 315.2 +/-
      16.4 nS (n = 37 for both P < 0.001). Most of the kinetic and steady-state
      properties of INa were unchanged after axotomy.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7511690
TI  - Nature and possible functions of interferons secreted by the preimplantation pig
      blastocyst.
AB  - In several ungulate species, the preimplantation trophoblast, among various
      secretions, produces large amounts of antiviral activity that was identified as
      interferon (IFN). IFNs (types I and II) are pleiotropic cytokines, which in
      addition to a potent antiviral activity, exert multiple effects on cell growth
      and differentiation, in particular on the cells of the immune system. In
      ruminants, trophoblastic IFN, or trophoblast protein-1 (TP-1), was found to
      consist of a multigenic family related to type I IFN-omega. These IFNs exert
      hormone-like effects through receptors present on the endometrium, leading to the
      prolongation of luteal life-span and hence to sustained progesterone secretion.
      In pigs, a species in which the maternal recognition of pregnancy is controlled
      by conceptus-derived oestrogens, two IFNs have been found in the preimplantation
      trophoblast. The major species is IFN-gamma (type II), that so far had been found
      only in activated T lymphocytes and natural killer (NK) cells. Transcription of
      the IFN-gamma gene in the pig trophoblast differs from that in mature
      lymphocytes, since two mRNAs are present. The other component with antiviral
      activity is a novel type I IFN, distant in sequence from IFN-alpha, beta, omega,
      and containing seven cysteines in its deduced mature protein. These two unrelated
      IFNs are temporally co-induced, with maximal secretion at day 16 of pregnancy.
      Specific receptors for both IFNs have been found on endometrial epithelial cells,
      but not on the preimplantation trophoblast, suggesting a paracrine effect on the
      uterus. Different hypotheses as to their role(s) in the establishment or
      maintenance of implantation are discussed. Whereas an indirect anti-infectious
      (antiviral) protection of the conceptus by IFNs cannot be ruled out, arguments
      are presented that do not favour a role in the immune tolerance of the conceptus.

PMID- 7511688
TI  - Highly co-operative Ca2+ activation of intermediate-conductance K+ channels in
      granulocytes from a human cell line.
AB  - 1. To study Ca(2+)-activated K+ currents in dimethyl sulphoxide (DMSO)
      differentiated HL-60 cells (HL-60 granulocytes), we have combined the patch clamp
      technique with microfluorimetric measurements of the cytosolic free Ca2+
      concentration ([Ca2+]i). 2. Elevations of [Ca2+]i induced by the receptor agonist
      N-formyl-L-methionyl-L-phenylalanine (f-MLP), by cellular spreading or by the
      Ca2+ ionophore ionomycin, activated whole-cell currents. The kinetics of the
      current elevations closely paralleled the kinetics of the elevations in [Ca2+]i.
      Cellular spreading induced oscillations in [Ca2+]i and parallel oscillatory
      changes in the amplitude of the recorded currents. 3. The reversal potential of
      the Ca(2+)-activated current was a function of the extracellular K+ concentration
      (56.1 mV per log [K+]), demonstrating that the underlying conductance was
      selective for K+. 4. The current was blocked by charybdotoxin, but insensitive to
      apamin. 5. The whole-cell current was inwardly rectifying. No time-dependent
      activation or inactivation of the current could be observed within the range of
      voltages tested (-100 to +100 mV). 6. The dependence of the current amplitude on
      the measured [Ca2+]i revealed a half-maximal activation at approximately 350 nM
      [Ca2+]i, and a highly co-operative activation by [Ca2+]i with an apparent Hill
      coefficient of approximately 8. Neither the half-maximal activation by [Ca2+]i
      nor the apparent Hill coefficient depended on the voltage, and they were
      identical for Ca2+ elevations caused by the ionophore and the receptor agonist.
      7. Analysis of Ca(2+)-activated single-channel events in cell-attached recordings
      revealed an inwardly rectifying K+ channel with a slope conductance of 35 pS.
      Fluctuation analysis of the Ca(2+)-activated whole-cell current suggested an
      underlying single-channel conductance of a similar size (28 pS). 8. In summary,
      we describe a charybdotoxin-sensitive, intermediate-conductance Ca(2+)-activated
      K+ channel in HL-60 granulocytes. The characteristics of the Ca2+ activation of
      this current (i.e. sensitivity to submicromolar [Ca2+]i, high co-operativity and
      voltage independence) are similar to the Ca2+ activation of the apamin-sensitive
      small-conductance K+ channel. Our results also suggest that [Ca2+]i elevations
      are the predominant, if not the only, activators of this channel during
      physiological stimulation of HL-60 granulocytes.

PMID- 7511691
TI  - Nuclear control of early embryonic development in domestic pigs.
AB  - In mammals, growing oocytes have characteristically high levels of RNA synthesis.
      After the initiation of meiosis, that is germinal vesicle breakdown, this RNA
      synthesis ceases. Although there is limited evidence for RNA synthesis by the
      zygote, significant amounts of RNA synthesis do not occur until a species
      specific cell stage. In pigs, significant amounts of mRNA synthesis cannot be
      detected before the four-cell stage. There appear to be three qualitatively
      different periods of transcription during the four-cell stage. The first occurs
      during a short (< 2 h) G1 phase. The second, occurs after completion of DNA
      synthesis (S phase) about 16 h after cleavage to the four-cell stage, and the
      third occurs about 24 h after cleavage to the four-cell stage. Correlated with
      these changes in RNA synthesis are changes in nucleolar morphology, amino acid
      transport characteristics, protein production, mitochondrial morphology, and
      metabolism of the embryo. The mechanisms that regulate initiation of RNA
      synthesis in early mammalian embryos appear to repress transcription. A state of
      transcription permissiveness then follows that sets into motion the
      differentiation programme.

PMID- 7511692
TI  - Synthesis, characterization, and biological activity of a new potent class of
      anti-HIV agents, the peroxoniobium-substituted heteropolytungstates.
AB  - The mono- and trisubstituted peroxyniobium polyoxotungstates of formulas
      [(CH3)3NH]7[Si-(NbO2)3W9O37], Cs7[Si(NbO2)3W9O37], alpha-K5[Si(NbO2)W11O39] and
      alpha-[(CH3)3NH]5[Si(NbO2)-W11O39], have been prepared, purified, and
      characterized spectroscopically by 29Si NMR, 183W NMR, and IR. The presence of
      peroxo groups was verified by the yellow color of the product and quantified by
      iodometric titration. The potency of both the complexes and the precursor
      complexes was evaluated in human peripheral blood mononuclear cells (PBMC)
      acutely infected with human immunodeficiency virus type 1 (HIV-1). Hexaniobate
      (K7H[Nb6O19]) was the least effective with a median effective concentration
      (EC50) of > 100 microM, while Cs7[Si(NbO2)3W9O37] was one of the most effective
      compounds with an EC50 of 1.0 microM. None of the compounds were toxic to
      uninfected PBMC with the exception of alpha-K8[SiW11O39], which had a median
      inhibitory concentration (IC50) of 79 microM. The potency and selectivity of the
      complexes against HIV-1 reverse transcriptase was also evaluated and shown to be
      quite high (IC50 values from 0.03 to 0.06 microM). The trimethylammonium salts of
      the complexes were tested for their ability to inhibit the interaction between
      gp120 and CD4 using a cell-free system. The complex [(CH3)3NH]7[Si(NbO2)3W9O37]
      inhibited this interaction by 70% at 25 microM.

PMID- 7511693
TI  - Microvessel density and distribution in ductal carcinoma in situ of the breast.
AB  - BACKGROUND: Prior studies have suggested that microvessel density is an important
      prognostic factor in invasive breast cancer. However, the extent and distribution
      of microvessels in association with ductal carcinoma in situ (DCIS) have not been
      well defined. PURPOSE: Our goal was to determine the density and distribution of
      stromal microvessels in DCIS and to investigate the relationships among
      microvessel density, histopathologic features, HER2/neu oncogene expression, and
      tumor proliferation rate. METHODS: Of 61 consecutive cases of DCIS identified
      from hospital pathology reports, 55 cases were evaluated. Breast biopsy specimens
      had been preserved in paraffin blocks for each DCIS case. Histologic sections of
      formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin and
      immunostained for factor VIII-related antigen, the HER2/neu oncoprotein, and the
      proliferative-associated antigen detected by the Ki-S1 antibody. Factor VIII
      stained sections from each case were independently examined by two pathologists
      and overall tumor-associated stromal microvessel density was scored
      semiquantitatively on a 1+ to 3+ scale by each observer. Quantitative microvessel
      counts of DCIS-associated stromal microvessel density were performed. The
      presence or absence of a cuff of microvessels in immediate apposition to the
      basement membrane of involved spaces was also evaluated. RESULTS: A variable
      number of microvessels were found to be present in a diffuse pattern surrounding
      spaces involved with DCIS. Semiquantitative microvessel scores were 2+ in the
      majority of cases (53%); 22% of cases were 1+, and 25% were 3+. Quantitative
      microvessel counts ranged from 17 to 80 vessels per 100x field (0.45 mm2), with a
      mean +/- SD of 42.9 +/- 16.6. Comedo-type lesions were significantly (P = .004)
      more often associated with 3+ microvessel density than non-comedo-type lesions by
      semiquantitative assessment. As determined by both semiquantitative and
      quantitative analysis, respectively, the presence of prominent microvessel
      density was significantly associated with marked stromal desmoplasia (P = .05 and
      P = .04), HER2/neu expression (P = .03 and P = .0002), and high Ki-S1
      proliferation index (P = .05 and P = .01). Vascular cuffing around involved
      spaces was identified in 21 of the 55 cases (38%) and was not significantly
      associated with histologic features, HER2/neu expression, or Ki-S1 proliferation
      index. CONCLUSIONS: DCIS of the breast is characterized by two patterns of
      stromal microvessels. The first pattern is a diffuse increase in stromal
      microvessels surrounding involved spaces. This pattern is particularly prominent
      in comedo-type lesions with marked stromal desmoplasia. The second pattern is
      microvessel cuffing of involved spaces that is present in only a minority of
      cases and appears unrelated to histologic features evaluated, including DCIS
      subtype.

PMID- 7511694
TI  - Angiogenesis and risk of breast cancer in women with fibrocystic disease.

PMID- 7511695
TI  - Transferrin in the central nervous system of the shiverer mouse myelin mutant.
AB  - Transferrin, the iron mobilization protein, and its mRNA are normally present in
      oligodendrocytes. Previous reports using myelin mutants have shown both a
      decrease in transferrin protein and mRNA when the oligodendrocyte population is
      compromised. In this study the shiverer mouse mutant in which the oligodendrocyte
      population is numerically normal, but has both quantitatively diminished and
      qualitatively abnormal myelin was used. This animal model was chosen to address
      the question whether expression of the transferrin message and/or protein
      correlated more closely to the number of oligodendrocytes (normal) or the amount
      of myelin (abnormally low). A 1/2 to 2/3 decrease in transferrin protein occurred
      in all brain regions examined except for the spinal cord in the shiverer group
      compared to both heterozygous littermates and wild type controls. Levels of
      transferrin transcripts in the brain are not affected by the shiverer mutation.
      These results taken with previous reports from this laboratory indicate that the
      presence of oligodendrocytes is a requirement for normal expression of
      transferrin mRNA in brain but is not sufficient for normal values of the protein.
      The level of Tf protein correlates more closely with the amount of myelin present
      than it does with the numbers of oligodendrocytes present. These data are
      consistent with previous reports from our laboratory that transferrin
      accumulation by oligodendrocytes is associated with myelin production by these
      cells. These data further suggest transferrin mRNA may be constitutively
      expressed by oligodendrocytes and that the protein expression is regulated at the
      level of translation.

PMID- 7511697
TI  - Orthograde transport and release of insulin-like growth factor I from the
      inferior olive to the cerebellum.
AB  - Insulin-like growth factor I (IGF-I) and its receptor are expressed in
      functionally related areas of the rat brain such as the inferior olive and the
      cerebellar cortex. A marked decrease of IGF-I levels in cerebellum is found when
      inferior olive neurons are lesioned. In addition, Purkinje cells in the
      cerebellar cortex depend on this growth factor to survive and differentiate in
      vitro. Thus, we consider it possible that IGF-I forms part of a putative trophic
      circuitry encompassing the inferior olive and the cerebellar cortex and possibly
      other functionally connected areas. To test this hypothesis we have studied
      whether IGF-I may be taken up, transported, and released from the inferior olive
      to the cerebellum. We have found that 125I-IGF-I is taken up by inferior olive
      neurons in a receptor-mediated process and orthogradely transported to the
      cerebellum. Thus, radioactivity found in the cerebellar lobe contralateral to the
      injection site in the inferior olive was immunoprecipitated by an anti-IGF-I
      antibody, co-eluted with 125I-IGF-I in an HPLC column, and co-migrated with 125I
      IGF-I in an SDS-urea polyacrylamide gel electrophoresis. Time-course studies
      indicated that orthograde axonal transport is relatively rapid since 30 min after
      the injection, radiolabeled IGF-I was already detected in the contralateral
      cerebellum. Furthermore, transport of IGF-I from the inferior olive is specific
      since when 125I-neurotensin was injected in the inferior olive or when 125I-IGF-I
      was injected in the pontine nucleus, no radioactivity was found in the
      contralateral cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511696
TI  - Characterization of the cis-acting elements of the mouse myelin P2 promoter.
AB  - Myelin P2 is a basic protein of an apparent molecular weight of 14,800.
      Expression of P2 has been found largely in the cytosol of Schwann cells in the
      peripheral nervous system. Although the function of P2 is unknown, its striking
      homology to a family of fatty acid binding proteins has led to the idea that P2
      may function as a fatty acid transport molecule. To investigate the DNA elements
      that control the expression of P2, sequences 5' to the coding region were cloned
      upstream of the cat reporter gene. A series of 3' and 5' promoter mutants was
      constructed and their activity determined following transfection into secondary
      Schwann cells and the MT4H1 Schwann cell line. Using this strategy, we have
      identified a 217 bp silencer region and a 142 bp positive regulatory region. In
      addition, we have localized the 5' flanking sequences in the promoter that are
      responsive to cAMP induction and to the transcription factor CCAAT/enhancer
      binding protein (C/EBP).

PMID- 7511698
TI  - K252a potentiates epidermal growth factor-induced differentiation of PC12 cells.
AB  - Epidermal growth factor (EGF) induced short neurites in two different strains of
      PC12 cells. The length of the EGF-induced neurites was markedly increased in the
      presence of the protein kinase inhibitor K252a, which is known to inhibit
      differentiation induced by nerve growth factor (NGF). EGF-induced differentiation
      of PC12 required RNA synthesis and activity of the ras proto-oncogene product.
      EGF increased the levels of three neurofilament proteins and the mRNA level of
      two late response genes (SCG10 and 63) known to be induced by NGF. Together, EGF
      and K252a caused a greater increase in these mRNAs than did either agent alone.
      K252a did not alter the extent of EGF-induced autophosphorylation of the EGF
      receptor, but it did decrease the extent of receptor phosphorylation in the
      absence of added EGF. Thus, the ability of the EGF receptor to trigger neuronal
      differentiation may depend on the state of its phosphorylation at serine and/or
      threonine residues. Two other strains of PC12 did not extend neurites when
      exposed to EGF, even when K252a was also present. Thus, the differentiating
      effect of EGF on PC12 is PC12 strain-specific.

PMID- 7511699
TI  - NADPH-diaphorase histochemistry in the postnatal mouse cerebellum suggests
      specific developmental functions for nitric oxide.
AB  - NADPH-diaphorase histochemistry has been applied for the localization of nitric
      oxide synthase during the postnatal development of the mouse cerebellum. Staining
      for NADPH-diaphorase during the first week after birth was confined to some but
      not all laminae of the immature cerebellum: NADPH-diaphorase activity was located
      in the molecular/Purkinje cell layer and in inner parts of the internal granular
      layer. The external granular layer and the developing white matter were
      essentially unstained. Expression was earliest and very strong in parallel fibers
      and in the internal granule layer of the ventral part of the pyramis and the
      dorsal part of the uvula. Staining in the Purkinje cell layer was observed
      throughout the cerebellum. The presence of formazan deposits within Purkinje
      cells was verified by colocalization with calbindin D-28k immunoreactivity. The
      distribution of NADPH-diaphorase activity changed into the adult pattern between
      8 and 12 days of age: Within the molecular layer, basket cells and their
      processes became strongly stained. Reaction product within Purkinje cells
      gradually disappeared. Likewise, strongly stained parallel fibers were no longer
      detectable. These results suggest that nitric oxide is involved in different
      processes in cerebellar development.

PMID- 7511700
TI  - Expression of the receptor tyrosine kinase c-kit in oligodendrocyte progenitor
      cells.
AB  - The growth and differentiation of neural precursor cells in the central nervous
      system (CNS) are regulated by their response to polypeptide growth factors which
      interact with specific transmembrane receptor tyrosine kinases (RTKs). We
      demonstrate that rat oligodendrocyte-type 2 astrocyte (O-2A) glial progenitor
      cells, precursors of the myelin-forming cells in the CNS, express the
      transmembrane RTK c-kit, the gene product of the murine dominant white spotting
      (W) locus and receptor for stem cell factor. Expression of c-kit transcripts and
      immunoreactive protein is lost when O-2A progenitors differentiate into post
      mitotic oligodendrocytes. Analysis of developing rat brain revealed an increase
      in the expression of c-kit transcripts between postnatal days 10 and 12, a window
      of time preceding the emergence of oligodendrocytes and the onset of myelination
      in vivo. Expression of c-kit in vitro and in vivo suggests a role for this
      receptor and its ligand during oligodendrocyte development.

PMID- 7511701
TI  - Myelination in cerebellar slice cultures: development of a system amenable to
      biochemical analysis.
AB  - Myelin deposition and maintenance are critical to proper function of the
      mammalian nervous system. Previous investigations of myelination in the central
      nervous system (CNS) were hampered by the lack of an in vitro system that can
      faithfully reproduce in vivo events yet is amenable to biochemical investigation.
      We have developed a procedure, based on organotypic cultures, which permits
      efficient preparation of large numbers of cerebellar slice cultures that can be
      easily manipulated. Cultures have been examined to document myelination
      biochemically (by incorporation of [35S]sulfate into sulfolipids),
      immunohistochemically (by labeling the myelin components myelin basic protein and
      galactocerebroside), and morphologically (by both light and electron microscopy).
      We tested the effects of biologically active peptides and antibodies on
      myelination in the thin slices. The results indicate that the cultures provide an
      in vitro system that can be used to examine specific cellular events that occur
      during CNS myelination.

PMID- 7511702
TI  - Trophic effects of basic fibroblast growth factor (bFGF) on differentiated
      oligodendroglia: a mechanism for regeneration of the oligodendroglial lineage.
AB  - We have investigated the effect of basic fibroblast growth factor (bFGF) on the
      proliferation and phenotype of differentiated oligodendroglia. Using primary cell
      cultures enriched in oligodendrocytes but containing few O2A-oligodendrocyte
      progenitor cells, we demonstrate that bFGF treatment greatly increases the
      proportion of O2A cells while decreasing the proportion of galactocerebroside
      +(GalC+), myelin basic protein +(MBP+) oligodendrocytes, and the steady state
      levels of MPB mRNA. Complement mediated cell lysis experiments using the A2B5
      antibody to deplete existing O2A cells or the R-Mab antibody to deplete existing
      oligodendroglia show that bFGF elicits a rapid increase in the number of O2A
      cells in cultures previously depleted of O2A cells, but does not cause an early
      increase in O2A cells in cultures from which oligodendroglia had been removed,
      indicating that the oligodendrocytes are the source of the newly recruited O2A
      cells. This bFGF-mediated transition from oligodendrocyte to O2A cells occurs
      with a time course similar to the bFGF-induced increase of the proliferation rate
      of the GalC+ oligodendrocytes. Studies with purified, passaged cells of the
      oligodendroglial lineage show that bFGF augments oligodendroglial
      dedifferentiation and proliferation in chronologically adult oligodendrocytes and
      in the virtual absence of other cell types. We have thus demonstrated that mature
      oligodendrocytes are induced by bFGF to dedifferentiate and proliferate,
      suggesting a mechanism for regeneration of the oligodendroglial lineage following
      demyelinating disease.

PMID- 7511704
TI  - Immunolocalization of proteolipid protein peptide 103-116 in myelin.
AB  - Determination of the topographic orientation of proteolipid protein (PLP) within
      myelin is part of an overall understanding of the functions of PLP and the roles
      of its multiple domains in diseases that primarily affect central nervous system
      (CNS) myelin. As part of an analysis of PLP orientation, two mouse monoclonal
      antibodies (mAb) and a rabbit antiserum against a synthetic peptide corresponding
      to PLP residues 103-116 (YKTTICGKGLSATV) were tested for their reactivity on
      compact CNS myelin. By ELISA, the antibodies react with intact PLP and PLP
      residues 103-116, but not with other PLP peptides. Ultrathin cryosections of
      adult rat optic nerve were immunostained and antibody binding was localized using
      appropriate second antibodies coupled to 1 nm gold particles that were visualized
      by silver enhancement. Localization of the particles on the major or intermediate
      dense lines was determined by three independent observers. Using the PLP peptide
      mAb and the polyclonal antibody, we demonstrated that > or = 71% of the particles
      were localized on the major dense line. At least 66% of particles directed
      against myelin basic protein, which is known to occur on the major dense line,
      were also found in that location. These semiquantitative morphologic observations
      suggest that PLP residues 103-116 occur on the cytoplasmic face of the myelin
      membrane.

PMID- 7511703
TI  - Humoral immune recognition of proteolipid protein (PLP)-specific encephalitogenic
      epitopes in the SJL/J mouse.
AB  - SJL/J mice were immunized with human PLP as well as encephalitogenic PLP peptides
      139-151 and 178-191 and the resulting antibody responses examined for
      immunochemical specificity employing a panel of 17 synthetic PLP peptide ligands.
      All animals had demonstrable circulating titers of antibodies early in the
      humoral immune response to their respective encephalitogens, however, there was
      no clear qualitative correlation between antibody responses and the induction of
      EAE. In the majority of PLP immunized animals, determinant-specific antibody
      populations, including those against encephalitogenic centers, were not
      detectable in the presence of an anti-PLP antibody response. Antiencephalitogenic
      peptide antibodies were present in both 139-151 and 178-191 immunized animals
      regardless of clinical/histologic status. Neither group produced cross-reactive
      anti-PLP antibodies as detected by ELISA. In animals immunized with peptide 139
      151, only anti-139-151 antibody specificities were noted. In contrast, all
      animals immunized with peptide 178-191 had an antibody population cross-reactive
      with three other PLP peptides: 97-110, 209-217, and 215-228. As humoral immune
      responses can be demonstrated against PLP-specific encephalitogenic epitopes, the
      significance of these B cell responses should be considered in the context of
      their potential role in the development, modulation, and/or potentiation of EAE.

PMID- 7511705
TI  - The long-term down-regulation of dihydropyridine receptors by Bay K 8644 in PC12
      cells.
AB  - Treatment of PC12 cells with Bay K 8644 for 12 hr or more leads to an almost 80%
      decrease in the subsequent ability of Bay K 8644 to stimulate the uptake of
      radioactive calcium into the cells. This effect is a property of the S(-)isomer
      of Bay K 8644; pre-treatment with the R(+)isomer, now known to be a calcium
      channel blocker, has the opposite effect. This treatment is specific in that it
      does not interfere with the stimulation of calcium uptake by potassium, ATP, or
      nerve growth factor. Such treatment is accompanied by a 90% decrease in the
      ability of Bay K 8644 to stimulate the release of norepinephrine. The
      characteristics of the binding of [3H]isradipine to control and to treated cells
      indicates that the decrease in the effect of dihydropyridines is accompanied by a
      marked decrease in the number of dihydropyridine binding sites with no apparent
      change in the affinity of the remaining sites. The continued ability of
      depolarizing levels of potassium to stimulate calcium uptake and the induction of
      the protooncogene c-fos in Bay K 8644-treated cells indicates that the L-type
      calcium channels are still intact, but are simply unresponsive to dihydropyridine
      agonists.

PMID- 7511706
TI  - Posttranslational modification of glycine-extended substance P by an alpha
      amidating enzyme in cultured sensory neurons of dorsal root ganglia.
AB  - The terminal step in the biosynthesis of substance P is the conversion of its
      glycine-extended precursor to the mature, amidated peptide by the alpha-amidating
      enzyme. This posttranslational modification was demonstrated in cultured,
      dissociated sensory neurons of dorsal root ganglia from neonatal rats. An assay
      was developed to quantitate both substance P and its precursor peptide in these
      cells. More than 90% of these two peptides was present as mature peptide in
      uncultured cells. In contrast, after 8 days in culture, about 85% of the peptides
      was the precursor, which increased 200-fold, whereas the level of substance P
      itself tripled during this culturing period. Since alpha-amidating enzyme
      requires ascorbate for activity, this reducing agent was added to the culture
      medium. Ascorbate induced a dose-dependent rise in the percentage of amidated
      peptide, with an apparent Km of 20 microM. After 5 days of culturing in the
      presence of 500 microM ascorbate, substance P increased 8-fold, constituting 70%
      of the total. The alpha-amidating enzyme also needs copper for activity. Even
      with 500 microM ascorbate in the culture medium, the copper chelator
      diethyldithiocarbamate dose-dependently reduced substance P synthesis by the
      sensory neurons, with a concomitant increase in its precursor peptide. These
      results suggest the presence of alpha-amidating enzyme in sensory neurons of
      dorsal root ganglia. It is likely that conversion of other glycine-extended
      precursors to their mature peptides in cell cultures would also require ascorbate
      and copper.

PMID- 7511707
TI  - Differential changes in intestinal permeability following burn injury.
AB  - Increased gut permeability (GP) following burn injury has been implicated in the
      predisposition to sepsis and multiple systems organ failure (MSOF). Since
      previous studies have identified only "global" alterations in GP, we examined the
      jejunum, ileum, and colon individually for GP using probes of two different
      sizes: fluorescein isothiocyanate-dextran-3 (FDEX, molecular weight 4387 d) and
      horseradish peroxidase (HRP, molecular weight 40,000 d). Animals were examined
      for GP at 1, 2, or 4 days following burn. The GP was significantly increased in
      all segments combined following burn injury to both the small probe (FDEX, p <
      0.001) and the larger probe (HRP, p < 0.06) versus controls. The GP was
      significantly greater for FDEX versus HRP (p < 0.001). Jejunal permeability to
      FDEX and HRP increased most at 24 hours. Ileal and colonic GP to FDEX increased
      early also, but were higher at days 2 and 4. These results suggest that,
      following burn injury, there is differential GP that is size and site dependent,
      and that increased GP may last well beyond 24 hours postburn despite feeding.

PMID- 7511708
TI  - A review of the efficacy and safety of 7.5% NaCl/6% dextran 70 in experimental
      animals and in humans.
AB  - Recent years have seen a renewed interest in the use of hypertonic-hyperoncotic
      solutions as plasma volume expanders for the treatment of hemorrhagic
      hypotension. In particular, a number of studies in experimental animals have
      addressed the efficacy and safety of small-volume infusions of 7.5% NaCl/6%
      dextran 70 (HSD). Employing models of fixed volume or fixed pressure hemorrhage,
      HSD has improved survival and reversed many of the hemodynamic, hormonal, and
      metabolic abnormalities associated with hemorrhagic shock. In the few human field
      trials completed to date, HSD has been shown to be potentially beneficial in
      hypotensive trauma patients who require surgery or have concomitant head injury.
      Extensive toxicologic evaluations and lack of reports of adverse effects in the
      human trials indicate that, at the proposed therapeutic dose of 4 mL/kg, HSD
      should present little risk.

PMID- 7511709
TI  - [A case of CD56-positive peripheral T-cell lymphoma presenting with giant tumor
      of the gastrointestinal tract during the course].

PMID- 7511710
TI  - Serotonergic measures in blood and brain and their correlations in rats treated
      with tranylcypromine, a monoamine oxidase inhibitor.
AB  - Tranylcypromine, a monoamine oxidase inhibitor, was administered to male Wistar
      rats in order to investigate its effects on blood and brain serotonin related
      substances after 1, 4, and 24 h following injection and possible relations
      between serotonergic measures in central nervous system and periphery. The dose
      of the drug tested was responsible for an increase in blood serotonin with a
      simultaneous fall in its metabolite 5-hydroxyindoleacetic acid (5-HIAA) compared
      to either pretreatment or control values. These changes were the most marked
      after 4 and 24 h following tranylcypromine injection. Almost all brain areas
      studied (cerebellum, medulla, hypothalamus, striatum, midbrain, hippocampus, and
      cortex) were to be affected by monoamine oxidase inhibitor treatment. They
      exhibited a rise in serotonin content starting from 1 h after drug administration
      and lasted in many parts of the brain up to 24 h, which was accompanied by a
      parallel fall in 5-HIAA level. All these changes were significant when compared
      to baseline and control values. Alterations in blood serotonin correlated
      positively with changes in brain serotonin and negatively with brain 5-HIAA,
      while the opposite pattern of correlations was found regarding blood 5-HIAA and
      the content of serotonin and 5-HIAA in various brain areas studied. This pattern
      of correlations speaks in favor of an existence of mutual relations between blood
      and brain serotonin related substances. Our results suggest that blood serotonin
      and 5-HIAA may serve as an index of monoamine oxidase inhibitor action on the
      central serotonergic system.

PMID- 7511711
TI  - Effects of endothelins on fluid and NaCl absorption across the jejunum
      anesthetized dogs.
AB  - The aim of this study was to investigate the effects of endothelins on fluid the
      NaCl absorption across the jejunum, the jejunal fluid and NaCl absorption and
      mesenteric hemodynamics in jejunal loops in anesthetized dogs during infusion of
      saline, endothelin-1 or endothelin-3 into the superior mesenteric artery.
      Infusion of endothelin-3 decreased the net fluid, Na+, and Cl- absorption;
      however, saline and endothelin-1 had no effect. To investigate the role of nitric
      oxide and soluble guanylate cyclase activation in the mechanisms underlying
      endothelin-3-induced decrease in fluid and electrolyte absorption, measurements
      were obtained in the presence of the nitric oxide synthesis inhibitor, nitro-L
      arginine methyl ester (L-NAME) or the soluble guanylate cyclase inhibitor,
      methylene blue. The endothelin-3-induced decrease in absorption was not
      influenced by the pretreatment with inhibitors. These results suggest that the
      endothelin-3 response was not mediated by nitric oxide or soluble guanylate
      cyclase.

PMID- 7511713
TI  - [The effect of absorbent materials with drugs on wound healing].
AB  - Absorptive hydrophilic materials (MAH) containing dioxydin and terrilytin as drug
      components were studied in experiments on guinea pigs infected with K-11 strain
      of E. coli. The results showed that the wounds in animals who did not receive
      treatment were cleaned by the 14th day, while the wounds in animals treated by
      applications of MAH with dioxydin and terrilytin became clean on the 3rd day, i.
      e. 5 times quicker. Absorptive hydrophilic materials containing dioxydin and
      teriilytin were easily handled, easily applied and removed, they did not injure
      the granulation tissue, and intensified growth of peripheral epithelialization.
      Thus, experimental study showed absorptive hydrophilic materials containing
      dioxydin and terrilytin to be highly effective in the treatment of purulent
      wounds, which allows them to be recommended for clinical use.

PMID- 7511712
TI  - [The polymer sorbent regenkur in the treatment of suppurative wounds].
AB  - Clinico-laboratory tests of the new Soviet polymer sorbent Regenkur obtained on
      the basis of rarely cross-linked cellulose ester were conducted on 60 patients
      with acute purulent diseases of the soft tissues in the surgical clinic, Sechenov
      Medical Academy. In treatment with sorbent applications the number of
      microorganisms reduced by several factors on the 3rd-5th day; on the average, the
      term of wound cleansing was 4.6 days, granulations appeared on day 4.3 and
      peripheral epithelialization on day 6.5. The duration of hospital stay decreased
      by one third. Advantages of the new sorbent over those of the well-known foreign
      analogue Debrizan were revealed.

PMID- 7511714
TI  - Differential fibrotic stromal responses of host tissue to low- and high
      metastatic cloned Lewis lung carcinoma cells.
AB  - BACKGROUND: The relationship between host stromal responses and tumor invasion
      and metastasis is poorly understood. To gain new insights into this relationship,
      we compared the stromal response in tumor tissues formed by low- and high
      metastatic murine lung carcinoma cell lines. EXPERIMENTAL DESIGN: Mouse Lewis
      lung-carcinoma-derived cloned cell lines with different metastatic potentials
      (P29, LM12-3, and LM60-D6 cells with low-, medium-, and high-metastatic
      potentials, respectively) were subcutaneously injected, and the resultant tumor
      tissue was analyzed immunohistochemically for the localization of type I
      collagen, fibronectin, and tenascin, and biochemically for the levels of
      glycosaminoglycans. The activities of conditioned media of cultured tumor cells
      to stimulate DNA synthesis in BALB/c 3T3 cells in vitro were also examined.
      RESULTS: In the subcutaneous low-metastatic P29 tumor, fibrillar extracellular
      matrices and fibroblast-like cells surrounding tumor cells were stained strongly
      for type I collagen, fibronectin, and tenascin, but only weakly stained in the
      more highly metastatic LM12-3 and LM60-D6 tumors. Implantation of these cell
      lines into cerebrum, which does not normally contain interstitial stroma, gave
      same results. Morphometric analysis of the subcutaneous tumor tissues revealed
      significantly more fibroblast-like cells and mast cells in the P29 tumor than in
      the more highly metastatic tumors. Quantitative analysis of glycosaminoglycans
      present in tumor tissues showed that the hyaluronic acid content of the P29 tumor
      was more than 5 times that in the more highly metastatic tumors. Furthermore,
      serum-free conditioned medium prepared from the culture of P29 cells exhibited
      about 10 times higher mitogenic activity toward BALB/c 3T3 cells than the
      conditioned medium from the more highly metastatic cells. CONCLUSIONS: We found
      an inverse relationship between the host stromal response and spontaneous lung
      metastasis. The stromal response in the P29 tumor may be induced directly by
      tumor cells and/or indirectly via mast cell activation. This metastasis model
      should be useful in understanding the role of stromal response in tumor
      metastasis.

PMID- 7511715
TI  - Rickettsia conorii infection of C3H/HeN mice. A model of endothelial-target
      rickettsiosis.
AB  - BACKGROUND: Rickettsial diseases result from disseminated intraendothelial cell
      infection. The clinically critical conditions, meningoencephalitis and
      interstitial pneumonia, are associated with multifocal rickettsial vascular
      injury. EXPERIMENTAL DESIGN: C3H/HeN mice inoculated intravenously with either
      2.25 x 10(3) or 2.25 x 10(5) Rickettsia conorii (Malish 7 strain) were observed
      for illness with sacrifice of animals for evaluation of pathologic lesions and
      host responses by light and electron microscopy, rickettsial content and location
      by plaque assay, immunohistology, and electron microscopy, and immune response by
      cytokine analyses and serology. RESULTS: Mice inoculated with a high dose of
      rickettsiae established disseminated endothelial infection on day 1, became ill
      with progressive increase in rickettsiae on day 4, and died with vascular injury
      based meningoencephalitis and interstitial pneumonia on day 5 or 6. Mice
      inoculated with the low rickettsial dose became ill on day 5 and recovered by day
      10. Clearance of rickettsiae was associated with lymphohistiocytic
      perivasculitis. Rickettsial infection of Kupffer cells and hepatocytes led to the
      formation of transient hepatic granulomas. Infection-associated loss of the
      ability of spleen cells to secrete interleukin-2 on stimulation with concanavalin
      A suggested transient immunosuppression. CONCLUSIONS: This experimental infection
      provides the best available model for rickettsial disease with endothelial
      infection and injury, immune rickettsial clearance, regeneration of endothelium,
      and repair of the vascular lesions.

PMID- 7511716
TI  - Effect of protein synthesis inhibition by cycloheximide on lymphocyte
      circulation.
AB  - BACKGROUND: Lymphocyte recirculation is directed by glycoprotein adhesion
      molecules on lymphocytes and endothelial cells of lymphoid tissues. Lymphocyte
      circulation in different lymphoid tissues is dependent on the type of
      glycoprotein adhesion molecules present. In the present study, the effects of
      inhibiting new protein synthesis on the ability of lymphocytes to circulate and
      home to different lymphoid tissues was investigated. EXPERIMENTAL DESIGN: New
      Zealand White rabbits and Lewis white rats were treated with cycloheximide or
      buffer. Total circulating lymphocyte counts and lymphocyte subsets were measured.
      Rabbits were given autologous, 111indium-labeled lymphocytes to determine if
      there were changes in the organ distribution of lymphocytes after cycloheximide
      treatment. RESULTS: After cycloheximide treatment, the number of circulating
      lymphocytes but not neutrophils increased significantly by 2 hours in both
      rabbits and rats. T cells, B cells, and L-selectin-positive lymphocytes showed
      similar increases. Measurements of the distribution of the radiolabeled,
      autologous lymphocytes in cycloheximide-treated animals showed significantly
      greater numbers circulating in the peripheral blood and decreased numbers in
      Peyer's patches, mesenteric lymph nodes, and spleens compared with controls. In
      contrast, the number of radiolabeled lymphocytes in the lung was not decreased
      after cycloheximide administration. CONCLUSIONS: These results indicate that
      protein synthesis inhibition causes lymphocytosis due to decreased lymphocyte
      homing to mesenteric nodes, Peyer's patches, and spleen, but not lung. This
      effect was not specific for distinct lymphocyte subsets, including T cells, B
      cells, or lymphocytes expressing L-selectin. These data show that molecules
      modulating lymphocyte homing in some organs have rapid turnover rates and suggest
      that changes in homing during the inflammatory process can be rapidly regulated
      by changes in protein translation.

PMID- 7511717
TI  - In vivo measurement of corneal angiogenesis with video data acquisition and
      computerized image analysis.
AB  - BACKGROUND: Measurement of corneal angiogenesis is useful for quantitating the
      effects of angiogenic stimuli and for evaluating the efficacy of potential
      inhibitors of neovascularization. Because accurate methods to record the entire
      pattern of corneal neovascularization over time in individual living animals do
      not exist, we have developed a noninvasive method to achieve this goal.
      EXPERIMENTAL DESIGN: The technique couples video data acquisition methods with
      computerized analysis of the video images. A stereotactic holding and positioning
      device allows alignment of the cornea such that it is viewed in a known and
      repeatable way. Contrast between blood vessels and corneal stroma in the images
      is enhanced by illuminating the cornea with monochromatic light centered on the
      peak absorption of hemoglobin. For each observation, multiple overlapping images
      of the peripheral cornea are recorded on videotape and subsequently digitized
      with a computer image analysis system. Overlapping regions are found by either
      statistical cross-correlation or common object identification methods. A montage
      of nonoverlapping adjacent images is made. Background electronic signals are
      reduced and contrast is enhanced in each montage with the aid of image
      processing. Finally, vessel area is calculated by pixel counting after
      establishing the density range for vessel identification. To demonstrate the
      utility of the method, we measured over the course of 18 days, the total area of
      neovascularization in rabbit corneas cauterized with silver/potassium nitrate,
      and treated topically with either normal saline (control) or 1% prednisolone
      acetate (100 microliters four times daily for 10 days). The corneal angiogenic
      response was measured at the time of cautery and at selected intervals
      thereafter. RESULTS: The amount of angiogenesis in each control cornea increased
      progressively during the entire observation period. In contrast, the prednisolone
      treated corneas manifested less neovascularization than controls during the
      treatment interval. After treatment ended, the amount of corneal angiogenesis
      increased slightly in this experimental group. This method provided multiple data
      points from each animal. CONCLUSIONS: To date, accurate measurement of corneal
      neovascularization has been a time-consuming process yielding few data points for
      each animal studied. The new method described, accurately measures even small
      changes in the area of corneal neovascularization, and allows for multiple
      observations of the same animal. The technique as currently developed, however,
      is not applicable to corneas that are markedly opaque or associated with
      intracorneal hemorrhage.

PMID- 7511719
TI  - Cytokines in acute myocardial infarction: selective increase in circulating tumor
      necrosis factor, its soluble receptor, and interleukin-1 receptor antagonist.
AB  - Cytokines play a pathogenetic role in a variety of infective and inflammatory
      diseases. In the present study, we had two objectives: (a) to define the kinetics
      of tumor necrosis factor (TNF) in plasma after acute myocardial infarction (AMI)
      in patients treated with early thrombolysis, and (b) to measure other cytokines,
      interleukin-1 (IL-1) and TNF receptor antagonists, in plasma. TNF-alpha, but not
      IL-1 beta or IL-8, was present in plasma of 6 of 7 patients with severe AMI
      (Killip class 3 or 4). No TNF (< 50 pg/ml) was detected in a group of 11 patients
      with uncomplicated myocardial infarction (Killip class 1) or in control patients
      without AMI. Soluble TNF receptor type I and IL-1 receptor antagonist (IL-1Ra)
      were also significantly increased in the group with severe AMI compared with
      those with uncomplicated AMI. Circulating TNF is increased only in AMI
      complicated by heart failure at hospital admission. This finding may have
      diagnostic and therapeutic relevance.

PMID- 7511720
TI  - Replacement of L-Lys by D-Lys(NH2) in peptide Ala-Arg-Pro-Ala-Lys (peptide 6A)
      increases its coronary blood flow-promoting properties.
AB  - Peptide 6A, a degradation of B beta chain of fibrinogen, is known to increase
      coronary and femoral blood flow. In this study, we examined the effects of
      peptide 32, an analogue of peptide 6A on coronary blood flow in anesthetized
      dogs. Intracoronary administration of equimolar amounts of peptide 32 and peptide
      6A showed a greater (p < 0.05) increase in blood flow with peptide 32.
      Intravenous administration of peptide 32 also resulted in greater and longer
      lasting increase in coronary blood flow. The greater blood flow enhancing effect
      of peptide 32 than that of peptide 6A may relate to absence of its degradation by
      angiotensin converting enzyme.

PMID- 7511718
TI  - Beneficial effects of taurolidine in experimental pancreatitis.
AB  - Taurolidine has potent antiendotoxin and antimicrobial effects in vitro. This
      study assessed the effect of taurolidine in a well-described model of acute
      pancreatitis. Ninety-five male Wistar rats (250 g) were studied. Pancreatitis was
      induced by intraductal injection of 50 microliters of a 4% sodium taurocholate
      solution at a pressure of 25 cm water. Animals were randomly allocated to 1 of 10
      groups: 4 groups were used to characterize the model and there were 6 treatment
      groups. Taurolidine (100 mg/kg) or saline was administered intravenously at Time
      1, 4 hr, or 4 and 24 hr following induction of pancreatitis. Serum amylase,
      endotoxin levels, and blood cultures were assessed at 4 and 24 hr. Survival was
      documented at 1 week. Serum amylase levels were elevated in animals in whom acute
      pancreatitis was induced; however, there was no difference in serum amylase
      between animals treated with taurolidine and those treated with saline. Positive
      blood cultures were more numerous in saline-treated groups. Treatment with
      taurolidine was associated with significantly (P < 0.01) lower endotoxin levels
      (14 +/- 8 pg/ml) compared with saline-treated animals (350 +/- 87 pg/ml).
      Taurolidine administration significantly improved survival compared with
      controls, when given at 4, 24, and 4/24 hr postinduction of pancreatitis (P <
      0.05). Taurolidine was beneficial in this model of acute pancreatitis.

PMID- 7511721
TI  - Barium decreases defibrillation energy requirements.
AB  - Certain antiarrhythmic drugs that inhibit myocardial repolarizing currents
      decrease defibrillation energy, but the effect of blocking particular currents on
      defibrillation is not well understood. We therefore investigated the effect of
      barium, a relatively selective blocker of inwardly rectifying potassium current
      (Ik1) on voltage and energy requirements for defibrillation in an open-chest dog
      model. Defibrillation energy and voltage requirements were assessed by delivering
      monophasic shocks through epicardial electrode patches at varying voltages to
      construct a dose-dependent curve of energy and voltage versus success in
      defibrillation. The energy and voltage for 50% success in defibrillation (E50 and
      V50, respectively) were determined by logistic regression. Monophasic action
      potential duration at 90% repolarization (MAPD90) was measured with a contact
      electrode, and ventricular refractory period (VERP) was measured. After baseline
      measurements were obtained of E50, V50, MAPD90, and VERP, saline (control) (n =
      6) or barium (1.1 mg/kg/min for 5 min followed by 0.25 mg/kg/min) (n = 11) was
      administered. Defibrillation voltage and energy requirements and
      electrophysiologic measures were repeated after 30 and 120 min of barium or
      saline infusion. In control animals, there was no significant change with time in
      V50 (2.0 +/- 12.4 and -0.2 +/- 16.0% at 30 and 120 min, respectively), VERP (+3
      +/- 5 and -2 +/- 3% at 30 and 120 min, respectively) or MAPD90 (+1 +/- 4 and -2
      +/- 6, at 30 and 120 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511722
TI  - Diethylamine/nitric oxide (NO) adduct, an NO donor, produces potent pulmonary and
      systemic vasodilation in intact newborn lambs.
AB  - Nitric oxide (NO), a labile humoral factor produced by vascular endothelial
      cells, is a potent vasodilator and an important mediator of pulmonary vascular
      tone. Nucleophile/NO adducts are a new class of compounds that spontaneously and
      predictively release NO. We investigated the hemodynamic effects of intravenous
      (i.v.) infusions of a recently developed NO-donor drug, the diethylamine-nitric
      oxide adduct (DEA/NO), in 17 intact newborn lambs. At rest, DEA/NO (1-2
      microgram.kg-1.min-1) produced dose-dependent decreases in mean pulmonary (from
      10.6 +/- 8.6 to 21.2 +/- 7.9%, p < 0.05) and systemic arterial pressure (from
      13.2 +/- 11.7 to 31.0 +/- 15.4%, p < 0.05). Similarly, during pulmonary
      hypertension induced by infusion of U46619, DEA/NO (0.5-2.0 micrograms.kg-1.min
      1) produced dose-dependent decreases in mean pulmonary (from 7.3 +/- 5.6 to 24.1
      +/- 13.3%, p < 0.05) and systemic arterial pressure (from 2.2 +/- 3.8 to 20.3 +/-
      12.9%, p < 0.05). Cardiac output (CO), heart rate (HR), systemic arterial blood
      gases, and pH were unchanged; atrial pressures decreased at higher doses.
      Equimolar infusions of S-nitroso-N-acetyl-penicillamine, nitroglycerin (NTG), and
      sodium nitroprusside (SNP) produced similar decreases in pulmonary and systemic
      arterial pressure. The nucleophile/NO adducts are potent vasodilators; their
      predictable and quantitative release of NO make them potentially useful research
      tools. In addition, because these compounds may decrease the incidence of
      tolerance and the risk from toxic metabolites associated with use of other
      nitrovasodilators, they may be clinically useful.

PMID- 7511723
TI  - Antiarrhythmic agent, MS-551, protects against pinacidil + hypoxia-induced
      ventricular fibrillation in Langendorff-perfused rabbit isolated heart.
AB  - We studied the electrophysiologic and antifibrillatory effects of the class III
      agent MS-551 in a rabbit isolated heart model in which ventricular fibrillation
      (VF) occurs reproducibly under conditions of hypoxia/reoxygenation in the
      presence of the ATP-dependent potassium channel opener, pinacidil. Ten minutes
      after MS-551 or vehicle administration, addition of pinacidil (1.25 microM) to
      the buffer was followed by a 12-min hypoxic period and 40-min reoxygenation. At a
      low concentration of MS-551 (1.0 microM), VF occurred in 5 of 6 hearts, the same
      incidence as in the control group (5 of 6). In contrast 0 of 6 hearts treated
      with 15 microM MS-551 developed VF (p < 0.05 vs. vehicle). Ventricular effective
      refractory period (VERP) was determined in a separate group of isolated hearts (n
      = 13). Pinacidil alone, during normoxic perfusion, decreased VERP 48 +/- 11% (p <
      0.05) 15 min after exposure. Five minutes of hypoxia alone also decreased VERP
      (57 +/- 8%, p < 0.05). Under normoxic conditions, MS-551 increased ERP 31 +/- 10%
      (p < 0.05 vs. baseline). VERP prolongation by MS-551 was reduced in the presence
      of pinacidil but remained 22 +/- 6% (p < 0.05) above baseline. The results
      suggest that VERP shortening owing to pinacidil-mediated ATP-dependent K+ channel
      opening is associated with development of VF in isolated heart. MS-551 attenuates
      the pinacidil-mediated decrease in VERP and prevents pinacidil+hypoxia
      reoxygenation-induced VF. Because pinacidil and hypoxia open myocardial KATP
      channels, putatively decreasing VERP, MS-551 may exert its antifibrillatory
      effect through partial blockade of KATP channels.

PMID- 7511724
TI  - Isolated, perfused rabbit ear artery: a model for studying segmental
      vasoconstriction and dilatation.
AB  - Severe increases in blood pressure (BP) are associated with a segmental pattern
      of constriction and dilatation in small arteries and arterioles, but the
      pathogenesis is poorly understood. We showed that the isolated, perfused rabbit
      ear artery typically develops segmental constriction and dilatation when
      intraluminal pressure is > 160-180 mm Hg during field stimulation of perivascular
      nerves (> 6 Hz) or extra- or intraluminal infusions of norepinephrine (NE > 10(
      7) M) or phenylephrine (PE) (> 5 x 10(-7) M). Light, transmission, and scanning
      electron microscopy showed that the dilated vessel segments initially show
      endothelial injury with no smooth muscle lesions. After repeated or prolonged
      exposure to high intraluminal pressure, dilated segments manifest extensive and
      severe endothelial and smooth muscle damage. Dilated regions also became
      abnormally permeable to tracer particles (ferritin). Constricted segments did not
      show evidence of endothelial or smooth muscle injury or hyperpermeability. These
      changes, i.e., segmental vasoconstriction/dilatation, hyperpermeability, and
      vessel wall damage localized to dilated segments, are comparable to those that
      occur in small arteries and arterioles during severe hypertension. We discuss the
      potential usefulness of the isolated ear artery as a model for studying the
      pathogenesis and morphology of segmental vasoconstriction/dilatation.

PMID- 7511725
TI  - Dose-dependent cardiotoxic effect of amiodarone in cardioplegic solutions
      correlates with loss of dihydropyridine binding sites: in vitro evidence for a
      potentially lethal interaction with procaine.
AB  - Increasing evidence suggests that amiodarone treatment may represent a potential
      risk in patients exposed to cardiac surgery. Conversely, amiodarone has been
      suggested to be beneficial as an additive to cardioplegic solutions, but its use
      has not been tried in vivo. We evaluated hemodynamic, ECG, and possible
      toxicologic effects of amiodarone when added to the cardioplegic solution. Pigs
      weighing (70 +/- 2 kg, n = 24) were exposed to cardiopulmonary bypass (CPB) and
      hypothermic cardiac arrest for 1 h with Bretschneider's (BS) or St. Thomas'
      Hospital (St. Th.) cardioplegic solution. Amiodarone or the solvent was added to
      the solutions. Only pigs receiving the lowest dose of amiodarone (0.028 mg/g
      tissue) could be weaned from bypass. Higher doses resulted in graded myocardial
      contractures without recovery of electrical activity. Electron microscopy showed
      severely disintegrated myocytes and swollen mitochondria in amiodarone-exposed
      hearts. No changes in equilibrium binding characteristics were observed for beta
      adrenoceptors, whereas maximum binding capacity (MBC) and receptor affinity for
      voltage-operated Ca2+ channels were dose-dependently decreased (mean 73%, p <
      0.0005; 105%; p < 0.05). Ca2+ paradoxlike findings similar to those in pigs were
      inducible in isolated, in vitro perfused rat heart exposed to normothermic or
      hypothermic chemical arrest with BS and amiodarone. This model was therefore used
      to evaluate whether the observed myocardial damage was associated with excessive
      tissue Ca2+ accumulation. Addition of amiodarone to BS was associated with a
      significant increase in 45Ca2+ content in the heart, irrespective of temperature.
      Only 2 of 13 hearts recovered some degree of mechanical activity during
      reperfusion. When procaine (an antiarrhythmic drug with membrane-stabilizing
      properties, an effect that is potentiated by amiodarone) was removed from BS,
      45Ca2+ accumulation did not differ from that in controls and mechanical activity
      recovered fully in 7 of 8 hearts. In conclusion, amiodarone added to Ca(2+)-free
      as well as Ca(2+)-containing cardioplegic solutions led to dose-dependent
      myocardial damage at reperfusion, irrespective of temperature. In parallel with
      clinical features was a reduction in maximum binding capacity and a decrease in
      affinity for the Ca2+ channel antagonist. Removal of procaine from BS prevented
      excessive Ca2+ accumulation and mechanical deterioration in isolated heart. We
      hypothesize that amiodarone administered under the conditions described may
      change the configuration of the Ca2+ channel, rendering it more permeable to
      Ca2+. Pharmacologic interaction between amiodarone and procaine apparently is at
      least partly responsible for the increased Ca2+ uptake and the stone-heart
      phenomenon during reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7511726
TI  - Reduction of infarct size during myocardial ischemia and reperfusion by lazaroid
      U-74500A, a nonglucocorticoid 21-aminosteroid.
AB  - Lazaroid U-74500A, a 21-aminosteroid that inhibits iron-dependent lipid
      peroxidation, was previously shown to have protective effects on neuronal
      viability in animal models of ischemic neurologic injury. To test the hypothesis
      that lazaroid enhances myocardial salvage after ischemia/reperfusion, lazaroid
      pretreated rats (2 mg/kg intravenously) (n = 26) and control rats pretreated with
      vehicle (n = 22) were subjected to 45-min left coronary (LCA) occlusion followed
      by 120 min of reflow. Lazaroid-pretreated rats and controls had similar ischemic
      risk areas (AR), as determined by phthalocyanine blue dye staining (47.2 +/- 2.3
      vs. 48.2 +/- 3.0%, p = NS, mean +/- SEM). Infarct size, measured by
      triphenyltetrazolium staining, was markedly reduced in lazaroid-treated rats as
      compared with controls (6.0 +/- 1.5 vs. 22.2 +/- 3.9%, p = 0.001, infarct
      size/ischemic RA x 100). There were no differences in systolic blood pressure
      (SBP), heart rate (HR), rate-pressure product (RPP), or maximum rate of left
      ventricular systolic pressure development (LVdP/dt) between groups during
      ischemia or reperfusion. Lazaroid pretreatment enhances myocardial salvage after
      45-min LCA occlusion and 2-h reflow in this animal model. This beneficial effect
      is independent of the hemodynamic determinants of myocardial oxygen demand.

PMID- 7511727
TI  - Acute increase in cardiac performance after triiodothyronine: blunted response in
      amiodarone-treated pigs.
AB  - Chronic hyperthyroidism is associated with increased myocardial contractility.
      The direct cardiac effect occurs through triiodothyronine (T3)-mediated synthesis
      of specific proteins. More recent studies have suggested that T3 may increase
      cardiac performance acutely, independent of protein neosynthesis. We wished to
      evaluate whether acutely administered T3 exerts an acute, dose-dependent
      hemodynamic response and adverse effects in normal and amiodarone-treated pigs.
      Closed-chest, fully anesthetized animals were used. For the dose-response study,
      4 control pigs received increasing doses (4, 20, 200, and 2,000 micrograms) T3 at
      15-min intervals, and the hemodynamic response and ECG features were monitored
      continuously. Another 4 control pigs received a single bolus of either of the
      four doses and were monitored for 60 min. Eight pigs that had received amiodarone
      (800 mg/day) for 10 days and 8 pigs that served as untreated controls were used
      in the hemodynamic study. Hemodynamic parameters were evaluated before and after
      a single bolus injection of 20 micrograms T3. Observation lasted no longer than
      45 min to assure that synthesis of new proteins would not contribute to changes
      in cardiac ability. T3 gave rise to a dose-dependent increase in cardiac
      performance within a certain dose range. Arrhythmias were also dose dependent and
      were not observed for the two lower doses. By 15 min after administration of 20
      micrograms T3, cardiac contractility had increased significantly and continued to
      increase throughout the observation period. After 45 min, peak left ventricular
      pressure (LVP) was increased by a mean of 27% (p < 0.001) and 19% (p = 0.013) in
      controls and amiodarone-treated pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511728
TI  - Converting enzyme inhibition improves congestion and survival in hypertensive
      rats with high-output heart failure.
AB  - The effects of angiotensin-converting enzyme (ACE) inhibitors in high-output
      heart failure have not yet been well established. We evaluated the effects of
      lisinopril (3 mg/kg/day) on hemodynamics, neurohormones, and survival in 10-week
      old spontaneously hypertensive rats (SHR) with aortocaval fistula. Sham-operated
      treated and untreated SHR served as controls. Cardiac output (CO) was determined
      by thermodilution method, and renal blood flow (RBF) was assessed by laser
      Doppler flowmetry. In sham-operated SHR, 2-week treatment with lisinopril
      decreased blood pressure (BP), left ventricular (LV) weight, and total peripheral
      resistance (TPR) (p < 0.01 each) and increased RBF and plasma renin activity
      (PRA) (both p < 0.05); CO and LV end-diastolic pressure (LVEDP) were unchanged.
      Fistula creation induced biventricular hypertrophy and high-output heart failure
      [increased LVEDP, CO, pulse pressure, and plasma norepinephrine (NE) and
      decreased RBF] with congestive signs (ascites, tachypnea). Lisinopril decreased
      LVEDP (p < 0.01), increased RBF, prolonged survival (both p < 0.05), and
      prevented ascites (0 vs. 46%) and increased PRA (p < 0.05) and attenuated the
      increase in plasma NE. Heart weight, BP, and CO were not affected by lisinopril.
      Thus, lisinopril ameliorated congestion and improved survival in SHR with fistula
      without compromising cardiorenal hemodynamics. Venous and renal dilatation and
      attenuation of vasoconstrictive systems may have contributed to the beneficial
      effects.

PMID- 7511729
TI  - Regression of left ventricular hypertrophy by converting enzyme inhibition in 12
      15-month-old spontaneously hypertensive rats: effects on coronary resistance and
      ventricular compliance in normoxia and anoxia.
AB  - The effects of trandolapril, a converting enzyme inhibitor (CEI), on left
      ventricular (LV) diastolic stiffness and coronary vascular resistance (CVR), were
      studied with an isolated heart preparation in 15-month-old spontaneously
      hypertensive rats (SHR). The hypertensive animals were treated for 3 months with
      trandolapril (0.3 mg/kg/day) (SHRT), and compared with untreated age-matched
      Wistar-Kyoto rats (WKY) and SHR. Trandolapril treatment resulted in 15%
      diminution in blood pressure (BP). In contrast, it completely normalized left
      ventricular (LV) weight. Untreated SHR, as compared with WKY, had a dilated LV
      and increased diastolic tissue stiffness. Trandolapril had no effect on either
      chamber or tissue stiffness. Five-minute anoxia resulted in the same dramatic
      increase in chamber stiffness in every experimental group. During anoxia, as
      during normoxia, tissue stiffness was still greater in SHR than in WKY. A major
      effect of CEI was to normalize the tissue stiffness of SHR under anoxia. Coronary
      vascular resistance (CVR) was increased in SHR as compared with WKY. Trandolapril
      improves CVR and significantly shifts the coronary pressure flow curve to the
      dilatory side. Both collagen concentration (approximately 2 mg/g) and the content
      in slow V3 myosin isoform, used as biologic markers of cardiac senescence, were
      the same in the three experimental groups, but higher than in young hearts.
      Trandolapril had no effect on these parameters. In semisenescent SHR, despite
      having rather slight effect on arterial pressure, trandolapril completely
      normalized LV weight. In addition, collagen content and its physiologic
      counterpart, tissue stiffness, were unaffected by 3-month treatment with
      trandolapril. Nevertheless, the anoxia-induced increase in LV tissue stiffness
      was improved by trandolapril in parallel with reduction in LV hypertrophy (LVH).

PMID- 7511730
TI  - Effect of clentiazem (TA-3090) with posttreatment on neurologic and histologic
      disorders of stroke-prone spontaneously hypertensive rats with history of stroke.
AB  - After stroke-prone spontaneously hypertensive rats (SHRSP) received a salt-loaded
      diet to accelerate onset of stroke, the therapeutic effect of clentiazem, a
      benzothiazepine Ca antagonist, on neurologic and histologic disorders was
      examined. Treatment with clentiazem (3, 15, and 30 mg/kg) orally twice daily
      (b.i.d.) for 28 days after the occurrence of stroke reduced neurologic symptoms
      and histologic changes of brain and kidney in a dose-dependent manner. Acute
      treatment with clentiazem (15 mg/kg, b.i.d.) administered immediately after
      stroke for 1 week not only almost completely abolished neurologic symptoms during
      treatment, but partially improved them even after treatment. Subacute treatment
      with clentiazem starting 10 days after stroke and continuing for 18 days also
      suppressed the neurologic signs. Both acute and subacute treatment improved
      cerebral histology. These results suggest that clentiazem treatment in the acute
      and subacute phases of stroke is beneficial.

PMID- 7511731
TI  - Antiplatelet effects of a novel antianginal agent, nicorandil.
AB  - Nicorandil (nicotinamidoethyl nitrate) is a novel vasodilator. Its vasodilator
      properties are related both to the nicotinamide and nitrate moieties. Classic
      nitrates such as nitroglycerin (NTG) and isosorbide dinitrate demonstrate in
      vitro inhibition of ADP-induced platelet aggregation. Such effects have been
      shown to occur in a dose-related manner, are potentiated by reduced thiols and by
      increasing preincubation time, and are associated with increases in intracellular
      cyclic GMP. We explored the effect of nicorandil on ADP-induced human platelet
      aggregation and the role of reduced thiol N-acetylcysteine (NAC) in modulating
      this response. Nicorandil significantly inhibited aggregation to ADP dose
      dependently (IC50 3.0 mM). These effects were associated with inhibition of
      fibrinogen binding to the platelet surface (IC50 2 mM). Addition of nicorandil
      after maximal ADP-induced aggregation was achieved resulted in disaggregation.
      Addition of a source of reduced thiol (NAC) potentiated the antiaggregatory
      effects of nicorandil threefold (p < 0.05). Platelet inhibition by nicorandil was
      also augmented by increase in duration of preincubation, with maximal effects
      observed at 180 min. Preincubation of platelets with 10 mM nicorandil resulted in
      attenuated inhibition of platelet aggregation on gel filtration and subsequent
      exposure to additional nicorandil, indicative of tolerance induction. Methylene
      blue (MB), an inhibitor of guanylate cyclase, significantly reversed nicorandil
      induced inhibition of platelet aggregation. Moreover, in accordance with this
      mechanism, nicorandil increased intracellular platelet cyclic GMP levels.
      Although the antiplatelet effect of nicotinamide was partially reversed by the K+
      channel inhibitor iberotoxin, preincubation with iberotoxin had no impact on
      inhibition of platelet aggregation by nicorandil.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7511732
TI  - Cardiodepressant actions of combined diltiazem and propranolol in dogs.
AB  - The cardiovascular actions of combined intravenous (i.v.) diltiazem and
      propranolol were studied in barbiturate-anesthetized dogs. When given alone,
      diltiazem increased cardiac output (CO) and P-R interval duration (P-R) while
      decreasing mean arterial pressure (MAP), heart rate (HR), and systemic vascular
      resistance (SVR). Propranolol alone decreased CO and HR while increasing SVR.
      With the same i.v. doses, combined infusion of diltiazem and propranolol rapidly
      resulted in depression of CO to levels similar to those achieved with propranolol
      beta-adrenoceptor blockade alone. The combination decreased MAP to levels
      achieved with diltiazem-induced calcium channel blockade. P-R increased beyond
      the durations produced by either drug given alone. Pharmacokinetic interactions
      were not apparent, although slight increases in propranolol plasma concentrations
      were observed during combined drug infusions. These studies support clinical
      observations that the cardiovascular effects resulting from a combination of
      diltiazem and propranolol may be attributed to the characteristic cardiovascular
      actions of each individual drug.

PMID- 7511733
TI  - Voltage dependence of cardiac delayed rectifier block by methanesulfonamide class
      III antiarrhythmic agents.
AB  - Voltage-clamp experiments were performed on isolated guinea pig ventricular
      myocytes to examine the voltage dependence of delayed rectifier block by
      methanesulfonamide channel blockers. Voltage-dependent channel block, in which
      block decreases as membrane potential is made more positive, could contribute to
      the phenomenon of reverse use dependence, in which the magnitude of the drug
      induced prolongation in action potential duration (APD) is inversely proportional
      to stimulation rate. To determine whether such a voltage dependence exists,
      concentration-response curves were generated for dofetilide, E-4031, sematilide,
      and D,L-sotalol at test potentials ranging from 0 to 60 mV. All agents blocked
      current in a manner consistent with selective blockade of the rapidly activating
      component of delayed rectifier current, IKr. The rank order of potency was E-4031
      approximately dofetilide > sematilide > sotalol. Block of tail currents by this
      class of compounds was more potent after test potentials to +60 mV than after
      those < or = 0-10 mV. These data are inconsistent with voltage-dependent channel
      block being a contributing factor to reverse use-dependence and suggest that
      other mechanisms must be responsible for this phenomenon.

PMID- 7511734
TI  - Rilmenidine-induced hypotension in conscious rabbits involves imidazoline
      preferring receptors.
AB  - The relative contributions of imidazoline-preferring receptors (IPR) and alpha 2
      adrenoceptors to hypotensive and bradycardic effects of intracisternal (i.c.)
      rilmenidine were investigated in conscious rabbits. We compared the antagonist
      potencies of two alpha 2-adrenoceptor antagonists, 2-methoxy-idazoxan (0.001-10
      micrograms/kg i.c.), which has very low affinity for IPR, and idazoxan (0.003-30
      micrograms/kg i.c.), which has high affinity for blocking IPR. We also compared
      the i.c. effects of the antagonists on responses to alpha-methyldopa (alpha-MD),
      a drug with centrally acting alpha 2-adrenoceptor agonist metabolites that have
      no affinity for IPR. Rilmenidine (22 micrograms/kg i.c.) and alpha-MD (400
      micrograms/kg i.c.) produced similar decreases in mean arterial pressure (MAP)
      (delta MAP = -23 +/- 2 and -24 +/- 2%, respectively) and in heart rate (HR)
      (delta HR = -11 +/- 1 and -9 +/- 2%, respectively, n = 30). The hypotension and
      bradycardia produced by alpha-MD and rilmenidine were completely reversed by 2
      methoxy-idazoxan, but 2-methoxy-idazoxan was 16 and 9 times more potent at
      restoring MAP and HR, respectively, after alpha-MD than after rilmenidine. In
      contrast, idazoxan was more potent in reversing the hypotension elicited by i.c.
      injections of rilmenidine than that elicited by alpha-MD. Idazoxan, however, had
      no effect on rilmenidine-induced bradycardia, but did dose-dependently reverse
      the decrease in HR produced by alpha-MD. In separate experiments, we observed
      that the doses of each antagonist drug in themselves did not modify MAP nor HR
      significantly, but a 10-fold higher dose of idazoxan (300 micrograms/kg) caused
      immediate although brief hypertension and tachycardia.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7511735
TI  - Are oxygen radicals implicated in the calcium paradox of the rat heart?
AB  - No reduction in creatine kinase (CK) release during standard Ca2+ paradox in the
      Langendorff-perfused rat heart was afforded by anoxic perfusion, nor by addition
      of the radical scavengers superoxide dismutase (150,000 U/L), catalase (150,000
      U/L), mannitol (15 or 50 mM), dimethylthiourea (DMTU, 10 mM), the antioxidant
      vitamin E (0.25 or 0.75 mM), or the iron chelator desferrioxamine (0.8 mM). Even
      under mild Ca(2+)-paradox conditions, achieved by (a) reducing the duration of
      the Ca(2+)-free period, (b) increasing [Ca2+]0 during the "Ca(2+)-free" period,
      or (c) reperfusing with 0.1 mM Ca2+, no protection was achieved by mannitol,
      DMTU, or desferrioxamine. Perfusion with N2 did not cause a reduction in CK
      release caused by caffeine or dinitrophenol or Ca2+ paradox. We conclude that no
      evidence supports the hypothesis that oxygen radicals are implicated in release
      of CK in Ca2+ paradox.

PMID- 7511736
TI  - Relation between acute myocardial uptake and hemodynamic and electrocardiographic
      effects of metoprolol in humans.
AB  - We studied myocardial disposition of metoprolol after a 4-mg intravenous (i.v.)
      bolus in 12 patients undergoing cardiac catheterization for investigation of
      chest pain, using a paired transcoronary sampling technique with simultaneous
      determination of coronary sinus blood flow (CSF). Myocardial metoprolol content
      (MMC) was then correlated with concomitant effects on hemodynamic and ECG
      parameters. Peak myocardial metoprolol content (1.89 +/- 0.40% of injected dose)
      was attained rapidly (2.67 +/- 0.38 min), but time to peak content was
      significantly delayed in the presence of extensive coronary artery disease.
      Residual MMC 17.5 min after injection was 49.1 +/- 8.7% of maximal MMC. Extent of
      coronary artery disease or variability in left ventricular (LV) systolic function
      did not influence peak MMC. Metoprolol induced slowing of spontaneous heart rate
      (HR, p < 0.05), reduction in LV +dP/dt (p < 0.0005), and prolongation of PR
      intervals (p < 0.05) with maximal changes 5-10 min after injection. Thus, time of
      peak hemodynamic effects of metoprolol was consistently delayed relative to time
      of peak MMC. We conclude that after i.v. injection, myocardial metoprolol
      accumulation in humans is rapid, with marked hysteresis between peak MMC and
      subsequent hemodynamic effects.

PMID- 7511737
TI  - Negative inotropic effect of propranolol is attenuated in underperfused feline
      heart with an acute ischemic region.
AB  - beta-Adrenergic blockade alleviates myocardial ischemia, probably largely through
      heart rate (HR) reduction. We hypothesized that the negative inotropic effect of
      beta-blockade, which is believed to be potentially dangerous, is attenuated in
      underperfused hearts with an acute coronary artery occlusion. We studied the
      effect of intravenous propranolol (1 mg/kg i.v.) in feline hearts with acute
      circumflex coronary artery (LCX) occlusion by cross-oriented segments in normally
      perfused and mildly underperfused left ventricular (LV) anterior wall. A control
      group (n = 10) was compared with a stenosis group (n = 9) in which the mean
      coronary perfusion pressure was reduced (91 +/- 4 g vs. 136 +/- 5 mm Hg, p <
      0.01). End-systolic pressure-length (ESP-ESL) relations during dynamic afterload
      increase and preload reduction were calculated to evaluate regional inotropy. HR
      and LV peak systolic blood pressure (LVSP) decreased in both groups after beta
      blockade (p < 0.05). Subendocardial and mid-myocardial blood flow measured by
      radiolabeled microspheres decreased in the control group (p < 0.05) but was
      unchanged in the stenosis group. Systolic shortening of circumferential segments
      also decreased in the control group (p < 0.05) but was unchanged in the stenosis
      group. ESP-ESL relations of circumferential segments shifted markedly rightward
      in the control group, whereas a modest rightward shift was noted in the stenosis
      group. This study in feline heart with acute LCX occlusion showed an attenuated
      negative inotropic effect of beta-blockade in underperfused LV anterior wall.

PMID- 7511739
TI  - Effects of a new Na+/H+ antiporter inhibitor on postischemic reperfusion in pig
      heart.
AB  - We investigated the effects of a new compound (3-methylsulfonyl-4
      piperidinobenzoyl) guanidine hydrochloride (HOE 694) known to inhibit the Na+/H+
      exchanger in a porcine model of ischemia/reperfusion. Ischemia was induced by
      coronary occlusion (twice for 10 min, with a 30-min reperfusion interval)
      followed by a 4-h reperfusion period. Treated animals (n = 8) received HOE 694 as
      a bolus (7 mg/kg) 20 min before ischemia and subsequently as a continuous
      infusion (0.07 mg/kg) throughout the experiment. Control pigs (n = 11) received
      vehicle. Regional wall function (percentage of segment shortening, % SS) of the
      treated animals was significantly improved as compared with that of controls
      after the 4-h reperfusion period (74.1 +/- 2.5 vs. 50.9 +/- 5.4, p < 0.005).
      Ventricular fibrillation (VF) could be prevented completely in treated pigs but
      occurred in 9 of 11 control animals (p < 0.001). Ultrastructural changes after
      ischemia and reperfusion were moderate and slightly abnormal in controls but much
      milder and completely recovered in the treated group, respectively. The tissue
      content of high-energy phosphates did not show a significant difference between
      groups. Inhibition of the sarcolemmal Na+/H+ antiporter with HOC 694 is
      antiarrhythmic and diminishes myocardial ischemic cell injury by preventing Na+
      overload.

PMID- 7511738
TI  - Protective effects of L-659,989, a platelet-activating factor receptor
      antagonist, in myocardial ischemia and reperfusion in rats.
AB  - The cardioprotective effects of L-659,989, a specific platelet-activating factor
      (PAF) receptor antagonist, were investigated in an ischemia/reperfusion model in
      rats. Pentobarbital-anesthetized rats were subjected to left main coronary artery
      occlusion (1 h) followed by reperfusion (1 h) (MI/R); Sham-operated rats were
      used as controls (Sham MI/R). Rats receiving vehicle showed reduced survival rate
      (60%), marked myocardial injury (necrotic area/total area = 54.5 +/- 6%; necrotic
      area/area at risk 76.6 +/- 6.7%), high serum creatine phosphokinase (CPK)
      activity (150 +/- 10 U/ml), and increased myocardial myeloperoxidase (MPO)
      activity in the area at risk (AR, 6.2 +/- 0.5 U x 10(-3)/g protein) and in the
      necrotic area (6.6 +/- 0.7 U x 10(-3)/g protein). PAF plasma levels increased
      significantly during reperfusion and peaked at 15 min of reperfusion.
      Administration of L-659,989 enhanced survival rate (80%), reduced myocardial
      damage (necrotic area/total area 25.6 +/- 3.5%; necrotic area/AR 34.6 +/- 5.4%),
      attenuated the increase in serum CPK (50 +/- 6 U/ml) and decreased MPO activity
      both in the AR (2.8 +/- 0.3 U x 10(-3)/g tissue) and in the necrotic area (2.3 +/
      0.5 U x 10(-3)/g tissue). Our results suggest that PAF-inducing adhesion and
      activation of polymorphonuclear leukocytes (PMN) plays a significant role in the
      injury associated with ischemia/reperfusion.

PMID- 7511740
TI  - Effects of angiotensin-converting enzyme inhibitors on glucose and lipid
      metabolism in essential hypertension.
AB  - Data of 52 patients, 29 women and 23 men aged 32-68 years (mean age 47 years)
      with essential hypertension, participating in three open therapeutic trials with
      either enalapril, lisinopril, or perindopril were evaluated to assess the effects
      of angiotensin-converting enzyme (ACE) inhibition on glucose and lipid
      metabolism. The 75-g oral glucose tolerance test (oGTT) was performed, and plasma
      glucose and insulin levels, as well as total cholesterol, high-density
      lipoprotein (HDL)-cholesterol, and triglycerides levels were determined before
      and after the 8- to 12-week treatment. Minor differences in the blood pressure
      (BP)-lowering effect and metabolic response were obtained with the ACE inhibitors
      studied; only lisinopril improved glucose tolerance significantly; blood lipids
      were not changed by any drug. The entire patient population showed only a slight
      reduction in 1-h postload glucose after treatment. More obvious improvement in
      glucose tolerance was evident in hypertensive patients who were glucose
      intolerant and/or insulin resistant (GI/IR, 53.8% of all), however. This subgroup
      also showed a slight but not significant increase in HDL-cholesterol and a
      decrease in triglycerides levels. Only a slight change or no change in plasma
      glucose, insulin, and lipid values was noted in hypertensive patients with normal
      glucose tolerance (NGT) and insulin sensitivity. These favorable effects were
      expressed only after ACE inhibitor monotherapy, but not when hydrochlorothiazide
      was added. The results indicate that a lack of stratification of hypertensive
      patients with regard to glucose tolerance or insulin sensitivity could be a
      confounding factor in evaluation of metabolic effects of ACE inhibitors.

PMID- 7511741
TI  - Hemodynamic effects of a new calcium antagonist, SR 33557, in patients with
      coronary artery disease and normal left ventricular function.
AB  - SR 33557 is a new calcium antagonist which in vitro demonstrated selectivity for
      smooth muscle over cardiac muscle. To assess the hemodynamic effects of SR 33557
      in humans, SR 33557 was administered intravenously (i.v.) in 9 patients with
      normal systolic left ventricular function [LV ejection fraction (EF) = 63.7 +/-
      8%] undergoing right and left catheterization. Baseline measurements were
      recorded before and during right atrial pacing (100 beats/min), after which 5 mg
      SR 33557 was infused in 10 min and hemodynamic parameters were continuously
      recorded until 30 min after discontinuation of the infusion. Effects of SR 33557
      were evident from discontinuation of the infusion, maximal between the tenth and
      twentieth min after discontinuation of the infusion. Without atrial pacing, the
      main effect of SR 33557 infusion was to decrease heart rate (HR) from 77.7 +/-
      10.7 to 61.9 +/- 9.3 beats/min (p < 0.001). Cardiac index (CI) did not change;
      stroke volume index (SVI) increased from 44.2 +/- 13 to 50.4 +/- 15 ml.m-2, (p <
      0.05). Mean arterial pressure (MAP) decreased from 104.7 +/- 29.6 to 94.3 +/-
      22.9 mm Hg (p < 0.05) with no change in filling pressures or systemic vascular
      resistance (SVR). Consequently, rate-pressure product (RPP) decreased from 8,211
      +/- 3,092 to 5,906 +/- 2,025 mm Hg.beat-1 (p < 0.01). Peak positive LVdP/dt
      decreased from 1,711 +/- 257 to 1,533 +/- 194 (p < 0.01). During the pacing
      phase, none of the hemodynamic parameters differed from baseline; especially peak
      positive LVdP/dt remained unchanged. SR 33557 has negative chronotropic action
      but shows no direct negative inotropic effect in patients with normal systolic LV
      function.

PMID- 7511743
TI  - Cardiovascular effects of basic fibroblast growth factor in rats.
AB  - We determined the effects of human basic fibroblast growth factor (bFGF) on blood
      pressure (BP) and heart rate (HR) in pentobarbital-anesthetized rats and examined
      the possible involvement of nitric oxide (NO) and prostanoids in these effects.
      Intravenous (i.v.) injections of bFGF (1, 7.5, and 15 micrograms/kg) induced dose
      dependent short-lasting decreases in BP followed by a striking increase in BP and
      HR variability. The BP and HR increases in variability were closely related (r =
      0.95; n = 20; p < 0.001). Pretreatment with a single intravenous (i.v.) dose of N
      omega-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg) almost suppressed (-90%)
      the cardiovascular effects of bFGF, an effect that was restored by a single dose
      of L-arginine (100 mg/kg i.v.). Similar suppression was observed with use of
      indomethacin (10 mg/kg i.v.). Indomethacin given 50-60 min after bFGF abolished
      the increased variability of BP and HR. We conclude that the BP decrease and the
      increase in BP and HR variability induced by bFGF involve release of both NO and
      vasoactive prostanoids.

PMID- 7511742
TI  - Effect of dietary polyunsaturated fatty acids on contraction and relaxation of
      rat femoral resistance arteries.
AB  - We investigated the effects of dietary polyunsaturated fatty acids (PUFA) derived
      from fish oil (n-3 PUFA) and plant seed oil (n-6 PUFA), in amounts relevant to
      human consumption, on the alpha 1-adrenoceptor-mediated contractile responses of
      isolated rat resistance arteries. Rats were fed semisynthetic diets, deriving 40%
      of total calories from fat. The control diet, which had sufficient linoleic acid
      to prevent essential fatty acid deficiency, had a polyunsaturated/saturated fatty
      acid (P/S) ratio of 0.3. The n-3 PUFA were given as a daily oral supplement of
      fish oil. For the n-6 PUFA diet, the proportion of linoleic acid in the diet was
      increased to obtain P/S ratio of 2.0. Diets were administered for 8 weeks. At the
      end of the feeding period, second-order branches of the femoral artery (< 300
      micros diameter) were mounted in pairs in an isometric myograph, and responses to
      norepinephrine (NE) 3 nM-10 microM with addition of yohimbine 1 microM and
      timolol 1 microM were examined. Subsequently, the vessels were preconstricted
      with NE to 60% of their maximal response and relaxation to acetylcholine 1 nM-0.1
      mM was observed. Dietary n-3 PUFA supplements led to attenuation of the
      contractile responses of isolated resistance arteries (p < 0.01, repeated
      measures analysis of variance, ANOVA-RM) versus control. The n-6 PUFA diet did
      not exert this effect although there was a downward trend. Diet did not affect
      EC50 values for NE. Neither n-3 nor n-6 PUFA diet influenced relaxation
      responses. The fatty acid composition of myocardial phospholipid fractions was
      significantly altered by both diets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511744
TI  - Effects of an angiotensin II receptor antagonist, CV-11974, on angiotensin II
      induced increases in cytosolic free calcium concentration, hyperplasia, and
      hypertrophy of cultured vascular smooth muscle cells.
AB  - The effects of CV-11974, a potent nonpeptide antagonist of the angiotensin II
      (AII) type-1 receptor (AT1), on cytosolic free calcium concentration ([Ca2+]i),
      hyperplasia, and hypertrophy of cultured vascular smooth muscle cells (VSMC) from
      rat aorta were studied. [Ca2+]i was measured by fura 2, and hyperplasia and
      hypertrophy were determined by incorporation of [3H]thymidine and [3H]leucine,
      respectively. CV-11974 had no effect on [Ca2+]i itself, but suppressed 10(-7) M
      AII-induced increase in [Ca2+]i dose dependently at concentrations from 10(-10) M
      and completely at 10(-7) M. CV-11974 suppressed both Ca2+ release from
      intracellular Ca2+ stores and Ca2+ influx from the extracellular space. However,
      CV-11974 had no effect on the increases in [Ca2+]i induced by prostaglandin F2
      alpha (PGF2 alpha), a potent vasoconstrictor, or ionomycin, a Ca2+ ionophore.
      These results indicate that the suppressive effects of CV-11974 act on the
      binding of AII and its specific receptors. AII 10(-7) M increased the synthesis
      of DNA and protein to 1.5 and 1.7 times the control values, respectively. CV
      11974 had no effect on synthesis of DNA or protein, but suppressed the AII
      stimulated synthesis of DNA and protein dose dependently at concentrations > or =
      10(-8) and 10(-10) M, respectively and completely at 10(-6) M. These results
      indicate that AII increases [Ca2+]i and synthesis of DNA and protein in VSMC
      through activation of AT1. CV-11974 showed no partial agonistic effects on AII.
      Thus, CV-11974 may act not only as an antihypertensive agent, but also as an
      inhibitor of vascular injury stimulated by AII.

PMID- 7511745
TI  - Pharmacologic profiles of YM934, a novel potassium channel opener.
AB  - Pharmacologic profiles of YM934, a newly synthesized 1,4-benzoxazin derivative K
      channel opener were evaluated in in vitro and in vivo experiments. In isolated
      rat portal vein, YM934 and a benzopyran derivative K channel opener lemakalim
      inhibited the frequency of spontaneous rhythmic contractions concentration
      dependently, with IC50 values of 14 and 38 nM, respectively. These inhibitory
      effects were competitively antagonized by glibenclamide (an ATP-sensitive K
      channel blocker; 10(-7)-3 x 10(-6) M). In isolated rabbit aorta, YM934 (10(-8)
      10(-6) M) and lemakalim (10(-8)-10(-6) M) relaxed the contractions induced by 20
      mM KCl concentration dependently but were ineffective against the contractions
      induced by 50 mM KCl. YM934 (10(-8)-3 x 10(-6) M) and lemakalim (3 x 10(-8)-10(
      5) M), but not the calcium antagonist nifedipine, relaxed the contractions
      induced by norepinephrine (NE 10(-6) M) or prostaglandin F2 alpha (PGF2 alpha 3 x
      10(-6) M) in the aorta. In pentobarbital-anesthetized dogs, YM934 (1-10
      micrograms/kg intravenously, i.v.) dose-dependently increased coronary artery
      blood flow (CBF), and decreased total peripheral resistance (TPR) and mean blood
      pressure (MBP). YM934 selectively increased CBF, but had little effect on
      vertebral, carotid, mesenteric, renal and femoral artery BF. These vasodilatory
      effects of YM934 were antagonized by glibenclamide. YM934 is a potent K channel
      opener and possesses potent vasodilatory effects, with particularly pronounced
      effects on the coronary artery. These effects of YM934 may, like lemakalim, be
      mediated by opening of ATP-sensitive K channels.

PMID- 7511746
TI  - Forskolin binding sites and G-protein immunoreactivity in rat hearts during
      aging.
AB  - Although the number of beta-adrenoceptors is unchanged with age in rat heart,
      both beta-adrenoceptor and postreceptor activation of adenylyl cyclase decreases
      with age. Pharmacologic data suggest that it is the amount of adenylyl cyclase
      enzyme units that limit activation of adenylyl cyclase with senescence, but
      direct quantitation of either G protein or adenylyl cyclase in rat heart with age
      is lacking. To quantitate the amount of adenylyl cyclase and G proteins with age
      directly, we assessed forskolin-stimulated adenylyl cyclase activity, the number
      of [3H] forskolin binding sites, and stimulatory G protein (Gs alpha) and
      inhibitory G protein (Gi alpha) immunoreactivity in the ventricles from 6- and 24
      month-old F-344 rats. The amount of Gs alpha and Gi alpha was unchanged with age
      in both crude membranes and partially purified membranes from ventricles. In
      contrast, there was a 32% decrease in the ability of forskolin to stimulate
      adenylyl cyclase maximally and a 41% decrease in the number of forskolin binding
      sites with age. Sensitivity for forskolin activation was unchanged with age, but
      there was a slight increase in affinity for [3H]forskolin binding. The decrease
      in the amount of adenylyl cyclase with age correlates with the diminished
      capacity to activate adenylyl cyclase with age and may account for the reduced
      beta-adrenergic signal transduction observed in senescent rat heart.

PMID- 7511747
TI  - Prevention of rethrombosis after coronary thrombolysis in a chronic canine model.
      I. Adjunctive therapy with monoclonal antibody 7E3 F(ab')2 fragment.
AB  - We examined the efficacy of the monoclonal antibody (MoAb) 7E3 F(ab')2 fragment,
      an inhibitor of the platelet glycoprotein (GP)IIb/IIIa receptor, to prevent
      coronary artery rethrombosis after successful thrombolysis with rt-PA. The
      circumflex coronary artery of anesthetized dogs was instrumented with a flow
      probe, an electrode, and a stenosis. After recovery from the surgical procedure,
      the animals were reanesthetized on post-operative day 9, and vessel wall injury
      was induced with current applied to the intimal surface of the circumflex
      coronary artery. The resulting occlusive thrombus was aged for 30 min, and
      recombinant tissue plasminogen activator (rt-PA) was administered. The animals
      were allocated to receive either placebo or a single dose of 7E3 [0.8 mg/kg
      intravenous (i.v.) bolus] as the sole adjunctive agent. Ex vivo platelet function
      and coronary artery blood flow velocity were recorded on each of 5 consecutive
      days. Reocclusion and mortality were reduced significantly in animals treated
      with 7E3 as compared with the placebo-treated group. Significant inhibition of ex
      vivo platelet aggregation persisted for 48 h after a single injection of 7E3. The
      MoAb 7E3 F(ab')2 fragment is effective as the sole adjunctive agent with rt-PA
      for prevention of rethrombosis. The present study is unique in that it examined
      the efficacy of GPIIb/IIIa inhibition in an experimental model for an extended
      time, demonstrating the duration of antiplatelet therapy required to prevent
      rethrombosis after thrombolysis.

PMID- 7511748
TI  - Prevention of rethrombosis after coronary thrombolysis in a chronic canine model.
      II. Adjunctive therapy with r-hirudin.
AB  - We examined the effectiveness of the direct-acting thrombin inhibitor,
      recombinant hirudin (r-hirudin), for prevention of coronary rethrombosis after
      thrombolysis with recombinant tissue plasminogen activator (rt-PA) in a canine
      model of coronary artery thrombosis. The reocclusion rate of 15-30% associated
      with thrombolytic therapy emphasizes the need for adjunctive therapy to prevent
      rethrombosis. We studied r-hirudin for its potential to prevent reocclusion in a
      model of coronary artery thrombosis/thrombolysis. The circumflex coronary
      arteries of anesthetized dogs were instrumented with a flow probe, an
      intraluminal electrode, and a ligature stenosis. The dogs were reanesthetized on
      the ninth postoperative day, and intimal injury was induced with an anodal
      current. After occlusive thrombus formation, tissue plasminogen activator (rt-PA)
      was administered. The animals were allocated to receive either placebo, r-hirudin
      [5 mg/kg intravenously (i.v.) bolus, 2 mg/kg/h i.v., for 3.5 h] or r-hirudin (5
      mg/kg i.v., bolus, 1 mg/kg/h i.v., for 12 h). Neither aspirin nor heparin was
      used. Ex vivo platelet function and coronary artery blood flow velocity were
      recorded on each of 5 consecutive days. Infarct size and residual thrombus weight
      were determined at the end of the protocol. r-Hirudin infusion (3.5 and 12 h)
      provided little benefit over rt-PA alone. Ex vivo platelet aggregation was not
      affected by r-hirudin. Little improvement in the incidence of reocclusion and
      mortality in a model of coronary artery thrombosis/thrombolysis resulted from
      adjunctive treatment with r-hirudin.

PMID- 7511749
TI  - Effects of endothelin-1 at pathophysiologic concentrations on coronary perfusion
      and mechanical function of normal and postischemic myocardium.
AB  - We assess hemodynamic, vascular, and hormonal effects of endothelin-1 (ET-1) at
      pathophysiologic levels on normal and ischemic myocardium. Thirty conscious
      chronically instrumented dogs were studied before, during, and after a 10-min
      coronary artery occlusion (CAO) performed either during ET-1 infusion (2.5
      ng/kg.min, n = 15) or during placebo infusion (n = 15). ET-1 infusion produced an
      increase in plasma ET-1 (from 1.3 +/- 0.1 to 11.5 +/- 1.1 pM, p < 0.0001) during
      CAO (pathophysiologic value). Left anterior descending artery (LAD) blood flow
      (measured by Doppler flow probe) decreased similarly during CAO with ET-1 or
      placebo (p = 0.0001, NS, ET-1 vs. placebo). Both endocardial and epicardial blood
      flows in ischemic regions also decreased (p = 0.0001) during CAO but were
      threefold greater with ET-1 than with placebo (endocardium 42 +/- 7 vs. 14 +/- 2
      ml/min/100 g, p = 0.003). No significant difference in myocardial blood flows
      between groups was observed in control regions. CAO produced increases (p <
      0.005) in heart rate (HR), mean aortic pressure (AOP), and ventricular pressures
      but no change in atrial pressures. The changes in these parameters were
      comparable in the ET-1 and placebo groups. Despite the greater residual flow
      during CAO, however, ET-1 decreased the function of the ischemic zone during
      reperfusion as assessed by systolic shortening (p < 0.05). Atrial natriuretic
      factor (ANF), unchanged during CAO with placebo, increased from 38.3 +/- 6.1 to
      53.3 +/- 10 pM with ET-1 (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511750
TI  - Action of KC-399, a newly synthesized potassium channel opener, on mechanical
      activity and 86Rb efflux in rat aorta.
AB  - To clarify the characteristics of KC-399, a newly synthesized potassium channel
      opener, we investigated the effects of KC-399 and lemakalim on the contractions
      induced by norepinephrine (NE 1 microM) and K+ (30 and 90 mM) and on 86Rb efflux
      in rat thoracic aorta. KC-399 (0.01-10 nM) and lemakalim (0.001-10 microM)
      induced relaxation in aortic rings precontracted with 30 mM K+ or NE, but not
      with 90 mM K+. The vasorelaxant effect of KC-399 was almost 500 times more potent
      than that of lemakalim. The vasorelaxation with KC-399 developed more slowly and
      was more resistant to washout than that induced by lemakalim. Glibenclamide (0.1
      1 microM), a blocker of ATP-sensitive K-channels, produced concentration
      dependent inhibition of the relaxant action of KC-399 in aorta treated with 30 mM
      K+. KC-399 (3-100 nM) and lemakalim (0.3-10 microM) stimulated 86Rb efflux in rat
      aorta; the potency of KC-399 was approximately 100 times greater than that of
      lemakalim. The effects of KC-399 on 86Rb efflux persisted after an 18-min washout
      period, but those of lemakalim did not. The stimulatory effects of KC-399 (10 and
      30 nM) and lemakalim (1 and 3 microM) on 86Rb efflux were also significantly
      reduced by glibenclamide (1 microM). These results suggest that KC-399 is a
      potent and long-lasting vasodilator in vitro and that opening of the ATP
      sensitive K+ channel may be involved in its mechanism of action.

PMID- 7511751
TI  - Effects of lisinopril on stress-induced peak blood pressure and sodium excretion:
      a double-blind controlled study.
AB  - A stress test was performed before (S1) and after a 1-month treatment period (S2)
      in patients with essential hypertension, randomly allocated to receive either an
      angiotensin-converting enzyme inhibitor (ACEI), lisinopril (n = 10), or placebo
      (n = 10). The two groups were similar with regard to systolic and diastolic blood
      pressure (SBP, DBP), body weight, renal function, and 24-h sodium excretion. At
      S1, stress induced a significant increase in SBP of 18 +/- 9 mm Hg and in DBP of
      10 +/- 6 mm Hg and a significant reduction in sodium excretion from 258 +/- 105
      to 204 +/- 72 mumol/min. Stress-induced sympathetic stimulation was assessed by a
      significant increase in urinary norepinephrine (NE) excretion from 21 +/- 10 to
      26 +/- 10 micrograms/g creatinine. One-month treatment by placebo did not change
      stress-induced BP reactivity, sodium retention, or urinary NE excretion. In the
      lisinopril group, rest and stress BP were significantly reduced by the treatment.
      Stress-induced sodium retention was higher after 1-month placebo treatment (72 +/
      78 vs 48 +/- 67 mumol/min), whereas this retention was significantly reduced by
      lisinopril (13 +/- 27 vs 69 +/- 60 mumol/min).

PMID- 7511752
TI  - Evidence for an alpha 1-adrenoceptor subtype mediating adrenergic
      vasoconstriction in Wistar normotensive and stroke-prone spontaneously
      hypertensive rat kidney.
AB  - We wished to characterise the alpha 1-adrenoceptor subtypes mediating renal
      vasoconstrictor responses in pentobarbital anaesthetised normotensive rats and
      stroke-prone spontaneously hypertensive rats (SPSHR). Renal nerve stimulation,
      close renal arterial administration of phenylephrine (PE, a mixed alpha 1a- and
      alpha 1b-adrenoceptor agonist) and methoxamine (a putative alpha 1a-adrenoceptor
      agonist) resulted in frequency and dose-dependent renal vasoconstrictor
      responses. Both dihydropyridine calcium channel antagonist amlodipine (200
      micrograms kg-1 plus 50 micrograms kg-1 h-1 and twice this dose) and the alpha 1a
      adrenoceptor antagonist 5-methylurapidil (5 micrograms kg-1 plus 1.25 micrograms
      kg-1 h-1 and twice this dose) suppressed renal nerve-, PE-, and methoxamine
      induced vasoconstrictions by between 21 and 59% (p < 0.05-0.001) in normotensive
      rats and SPSHR. The alpha 1b-adrenoceptor alkylating agonist chloroethylclonidine
      (5 micrograms kg-1 plus 1.25 micrograms kg-1 h-1 and twice this dose) attenuated
      renal nerve-mediated vasoconstrictions by 20% (p < 0.01), but not those induced
      by PE and methoxamine. This pattern of agonist and blocking drug interaction
      suggests that the renal postjunctional alpha 1-adrenoceptors require
      extracellular calcium and are sensitive to 5-methylurapidil, characteristics of
      the alpha 1a-adrenoceptor subtype. Moreover, a similar situation exists at the
      renal resistance vessels of SPSHR.

PMID- 7511753
TI  - Effects of acetylsalicylic acid on peripheral hemodynamics in patients with
      chronic heart failure treated with angiotensin-converting enzyme inhibitors.
AB  - Cyclooxygenase inhibitors may affect the hemodynamic status of patients with
      heart failure adversely and may also block the vasodilatory effects of
      angiotensin-converting enzyme (ACE) inhibitors in such patients. Relatively low
      doses of the cyclooxygenase inhibitor acetylsalicylic acid (ASA) are now used
      routinely in ischemic heart disease, the most important cause of heart failure.
      Therefore, we investigated the hemodynamic interaction between ASA and captopril
      in heart failure. In a randomized, cross-over study, 13 patients with congestive
      heart failure (CHF) who were already receiving maintenance treatment with an ACE
      inhibitor received a single dose of 25 mg captopril combined with 236 mg ASA or
      placebo. Peripheral blood flow was studied noninvasively by venous occlusion
      plethysmography of the calves. Liver blood flow was estimated from indocyanine
      green (ICG) clearance. Administration of captopril alone significantly decreased
      blood pressure (BP), and ICG clearance. Calf blood flow remained unchanged.
      However, after arterial occlusion, hyperemic calf blood flow persisted for
      longer. Captopril alone did not significantly change the plasma levels of the
      vasodilating prostaglandins PGI2 and PGE2 or the vasoconstricting thromboxane A2
      (TXA2). In contrast, captopril combined with ASA reduced the plasma levels of
      these vasoactive substances, with significant decreases in PGE2 and TXA2 as
      compared with captopril alone, yet the hemodynamic alterations after captopril
      plus ASA were similar to those observed after captopril alone. A single
      antithrombotic dose of ASA (236 mg) in 13 patients with CHF [New York Heart
      Association (NYHA) class II-IV] undergoing chronic treatment with ACE inhibitors
      had no discernible effect on hemodynamic status.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511754
TI  - Influence of dopamine and angiotensin II blockade on the acute response to
      unilateral nephrectomy in rats.
AB  - Unilateral nephrectomy (UNX) is followed by a prompt functional adaptation (as
      well as initiation of compensatory growth) in the contralateral kidney. We
      assessed the possibility that dopamine (DA) receptor antagonism and angiotensin
      converting enzyme inhibition may influence the acute natriuretic response to UNX
      of the remaining kidney in euvolemic anesthetized Sprague-Dawley rats with or
      without pretreatment by haloperidol or enalapril. Twenty to 80 min after UNX,
      urinary excretion of sodium and potassium approximately doubled and fractional
      excretion of lithium (an index of proximal tubular handling of sodium) increased
      by about one third in untreated rats, whereas glomerular filtration rate, renal
      plasma flow and mean arterial pressure (MAP) did not change significantly.
      Haloperidol infusion blunted the post-UNX increase in fractional excretion of
      lithium without affecting the natriuretic/kaliuretic response of the remaining
      kidney. Enalapril pretreatment resulted in lower MAP and marked renal
      vasodilation at baseline but no significant alteration in the response to UNX.
      These results indicate that the magnitude of post-UNX natriuresis is not affected
      by suppression of angiotensin II (AII) generation or blockade of DA receptors.
      The lithium clearance data suggest that the immediate natriuretic response to UNX
      can be ascribed to both a proximal and a distal tubular phenomenon.

PMID- 7511755
TI  - Action of MgSO4 differs from moricizine and verapamil on ouabain-induced
      ventricular tachycardia in normomagnesemic conscious dogs.
AB  - We performed a comparative study to determine whether acute administration of
      MgSO4, moricizine, and verapamil to conscious dogs with normal plasma magnesium
      levels (0.75 +/- 0.06 mM) terminates ouabain-induced ventricular tachycardia
      (VT). This arrhythmia is dependent on triggered activity (TA) resulting from
      delayed afterdepolarizations (DADs). In animals with surgically induced complete
      atrioventricular (AV) block, monomorphic VT was induced by programmed ventricular
      stimulation during continuous intravenous (i.v.) infusion of ouabain. At the
      moment of drug administration, VT persisted for at least 20 min, while the rate
      was stable for at least 5 min. A single dose of MgSO4 (100 mg/kg i.v.) abolished
      only VTs with cycle lengths > or = 320 ms (335 +/- 10 ms); VTs with faster cycle
      lengths (300 +/- 20 ms) were merely slowed, although the increase in plasma
      magnesium levels was considerable and comparable in both groups (3.9 +/- 1.6 and
      4.8 +/- 1.9 mM). In contrast, moricizine (2 mg/kg i.v.) and verapamil (0.5-1.0
      mg/kg i.v.) terminated both fast and slow VTs. The cycle length of VT ranged from
      280 to 320 ms (mean 300 +/- 15 ms) for moricizine and 260-330 ms (mean 300 +/- 25
      ms) for verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511757
TI  - Disparate inotropic and lusitropic responses to pimobendan in conscious dogs with
      tachycardia-induced heart failure.
AB  - Left ventricular (LV) inotropic and lusitropic responses to a calcium sensitizer,
      pimobendan, were compared between normal and failing hearts. Heart failure was
      induced by rapid ventricular pacing in 6 dogs instrumented with a micromanometer
      and a conductance catheter. The effects of pimobendan were evaluated in the
      conscious state before and after development of heart failure. Pimobendan dose
      dependently increased the slope of the end-systolic pressure-volume (P-V)
      relation (Ees) in both normal and failing hearts, whereas its magnitude was
      markedly attenuated in failing hearts. Heart rate (HR) was increased by
      pimobendan in normal heart but did not change in failing heart. LV relaxation,
      assessed by peak -dP/dt and the time constant of isovolumic pressure decay (Td),
      was substantially improved to the same extent in failing and normal hearts.
      Consequently, Ees and Td exhibited a hyperbolic relation over a wide range of
      contractility states. In normal heart, pimobendan caused a leftward shift of the
      diastolic P-V relation while maintaining a similar curve. In failing heart,
      however, this relation shifted directly downward with a concomitant increase in
      end-diastolic volume, indicating a reduction in the constraints on LV distention
      and a resultant increase in preload reserve. Thus, pimobendan accelerated LV
      isovolumic relaxation and improved distensibility in conscious dogs with
      tachycardia-induced heart failure despite the marked attenuation of inotropic
      responses.

PMID- 7511758
TI  - Renal morphology and function in dogs after treatment with the angiotensin
      converting enzyme inhibitor quinapril.
AB  - Angiotensin-converting enzyme (ACE) inhibitors have proven to be effective
      therapeutic agents for treatment of hypertension and congestive heart failure
      (CHF). Because of the role the renin-angiotensin system (RAS) plays in
      maintaining renal homeostasis, the effect these compounds have on renal function
      has been of interest. We assessed the effect of toxicologically significant doses
      of the new ACE inhibitor, quinapril, on renal function and morphology in dogs.
      Groups of 3 male beagle dogs were administered quinapril orally at daily doses of
      0, 25, 125, or 250 mg/kg for 13 weeks. After treatment, animals were anesthetized
      and assessed for clinical pathologic and renal functional disturbances under
      normal conditions and after volume expansion and diuresis. Renal histopathology
      was conducted on perfusion-fixed kidney. No adverse effects on sensitive measures
      of renal function were detected; changes observed were consistent with the
      pharmacologic consequences of ACE inhibition. Decreased serum Na+ and Cl- (< 10%)
      and hematocrit at 125 and 250 mg/kg, twofold increases in serum creatinine and
      blood urea nitrogen (BUN) at 250 mg/kg, and decreased arterial blood pressure
      (BP) (20%) were observed at all doses. Under baseline conditions, urine flow
      increased 81-123% in quinapril-treated animals as compared with controls and
      urine specific gravities decreased 16% relative to controls at 125 and 250 mg/kg.
      Microscopically, juxtaglomerular hypertrophy was observed at all doses. At 250
      mg/kg, minimal, widely scattered cortical tubular alterations were observed;
      glomerular lesions were not. No significant adverse effects of quinapril on renal
      morphology or function were observed at doses approximately 250 times the
      therapeutic dose.

PMID- 7511756
TI  - Effects of 5-(N,N-hexamethylene)amiloride on action potentials, intracellular Na,
      and pH of guinea pig ventricular muscle in vitro.
AB  - We examined the effects of 5-(N,N-hexamethylene)amiloride (one of the Na(+)-H+
      exchange blockers, HMA) and amiloride (AM) on action potentials (APs),
      intracellular Na+ activity, and pH using conventional and double-barreled ion
      selective microelectrodes in guinea pig papillary muscle in vitro. Papillary
      muscle preparations were superfused with HEPES-buffered solution, and
      intracellular Na+ (aiNa+) and H+ (intracellular pH, pHi) activities were measured
      in quiescent preparations without stimulation. HMA at a concentration of 1 microM
      began to induce prolongation of action potential duration (APD) and at
      concentrations > 10 microM induced a decrease in action potential amplitude
      (APA), depolarization of resting membrane potential (RMP), prolongation of APD
      and depression of the maximum upstroke velocity (Vmax). HMA exerted dose-, time-,
      and rate-dependent reduction in Vmax. AM began to prolong APD at a concentration
      of 10 microM and at 1 mM induced depolarization of RMP, decreased Vmax and
      induced significant prolongation of APD. HMA (100 microM) induced a decrease in
      aiNa+ by 2-3 mM, but exerted no effects on pHi in normal Tyrode's solution. Under
      conditions of intracellular acidosis induced by exposure to K(+)-free solution,
      HMA produced a further decrease in pHi. Our results provide direct evidence that
      HMA has a depressant action on cardiac Na+ channels and prolongs AP at
      concentrations that presumably affect Na(+)-H+ exchange in cardiac muscle.

PMID- 7511759
TI  - Mechanisms of the natriuretic effects of neutral endopeptidase inhibition in Dahl
      salt-sensitive and salt-resistant rats.
AB  - To explore the mechanisms of the renal effects of neutral endopeptidase (NEP)
      inhibition, the effects of an NEP inhibitor, candoxatril (UK 79,300; UK), in Dahl
      salt-sensitive (SS) and salt-resistant (SR) rats were examined. UK dose
      dependently decreased blood pressure (BP) in SS rats (20 mg/kg: 174 +/- 5 vs. 155
      +/- 8 mm Hg, p < 0.01) but not in SR rats. Urinary sodium excretion (UNaV) of
      both rat strains receiving high-salt diets was increased to a greater extent than
      that of rats receiving low-salt diets. Basal plasma atrial natriuretic peptide
      (ANP) level in hypertensive SS rats was higher than in SR rats (192 +/- 18 vs.
      118 +/- 24 pg/ml, p < 0.05). UK increased ANP levels in the plasma and urine two-
      and 11-fold, respectively. UK-induced increases in UNaV, urinary cyclic GMP, and
      plasma ANP concentrations were significantly augmented by coadministration of a
      clearance receptor agonist, C-ANF(4-23) or brain natriuretic peptide (BNP). Thus,
      the effects of NEP inhibition appear to be potentiated by the reduced receptor
      mediated metabolism of ANP. This may explain the greater response to the NEP
      inhibitor in Dahl rats with hypertension or high-salt feeding.

PMID- 7511760
TI  - Role of angiotensin in pressure overload-induced hypertrophy in rats: effects of
      angiotensin-converting enzyme inhibitors, an AT1 receptor antagonist, and
      surgical reversal.
AB  - The renin-angiotensin system (RAS) has been proposed to play a major role in
      causing the heart to hypertrophy during pressure overload. We examined whether
      blockade of this system by the angiotensin-converting enzyme (ACE) inhibitors
      enalapril (0.5 to 20 mg/kg p.o.) or ramipril (1.0 mg/kg p.o.) or the angiotensin
      receptor (AT1) antagonist losartan (3.0 mg/kg p.o.) could prevent pressure
      overload-induced hypertrophy. Pressure overload was produced by abdominal aortic
      constriction in rats. Cardiac hypertrophy was assessed by an increase in the
      ratio of left ventricular (LV) weight to body weight and total protein content of
      the left ventricle. Treatment with enalapril or ramipril, initiated 3 weeks after
      aortic banding and continued for 3 more weeks, failed to prevent the progression
      or cause regression of cardiac hypertrophy. Treatment for 6 weeks with ramipril
      initiated immediately after aortic banding also failed to prevent cardiac
      hypertrophy. Losartan treatment initiated 3 weeks after aortic banding and
      continued for 3 more weeks resulted in a slight but significant reduction in the
      extent of cardiac hypertrophy (45.6% hypertrophy in controls and 35.6%
      hypertrophy in losartan-treated animals, p < 0.05, n = 11 and 10, respectively).
      Surgical removal of bands 3 weeks after placement reduced cardiac hypertrophy to
      a greater extent than that observed in losartan-treated animals. These results
      suggest that angiotensin may not play a major role in causing pressure overload
      induced hypertrophy or in maintaining such hypertrophy.

PMID- 7511761
TI  - Cardiovascular profile of RWJ 29009, a new potassium channel activator, in
      anesthetized and conscious dogs.
AB  - RWJ-29009, (6S)-trans(-)-1-(6,7-dihydro-6-hydroxy-5,5-dimethyl-2-nitro-5 H
      thieno[3,2-b]pyran-7-yl)-2-piperidinone, is a structurally novel and extremely
      potent potassium channel activator that may be useful for treatment of
      hypertension and ischemic heart disease. We assessed the cardiovascular profile
      of RWJ 29009 in anesthetized and conscious dogs. RWJ 29009 (0.1-2 micrograms/kg
      intravenously, i.v.) dose-relatedly increased coronary blood flow (CBF) and
      decreased arterial pressure in anesthetized dogs. Total peripheral resistance and
      coronary vascular resistance were concurrently reduced without significant
      changes in heart rate (HR) or cardiac output (CO). Left ventricular (LV) dP/dtmax
      and myocardial contractile force were decreased only at the highest dose of 10
      micrograms/kg. Cromakalim (3-100 micrograms/kg), although much less potent, had a
      qualitatively similar profile. Glyburide pretreatment (5 mg/kg i.v.) shifted the
      dose response of RWJ 29009 for increasing CBF and decreasing arterial pressure to
      the right. The dose responses of cromakalim were similarly shifted to the right,
      whereas the effects of nifedipine on CBF and arterial pressure were not affected
      by glyburide. RWJ 29009 (0.3 and 1 microgram/kg) had no effect on myocardial O2
      consumption (MVO2) except for a transient increase immediately after
      administration of 1 microgram/kg. MVO2 returned to control 15 min after dosing,
      although CBF remained significantly increased. In conscious dogs, RWJ 29009 (0.3
      10 micrograms/kg, i.v. and orally, p.o.) produced dose-related increases in CBF
      and decreases in arterial pressure similar to those produced in anesthetized
      dogs, except that HR was increased concurrently. The i.v. and p.o. potency of RWJ
      29009 were comparable, indicating high oral bioavailability. Thus, RWJ 29009 is
      an extremely potent coronary and peripheral vasodilator with a cardiovascular
      profile similar to that of other potassium channel activators. Like those of
      other potassium channel activators, its mechanism of action appears to involve
      activation of ATP-regulated potassium channels.

PMID- 7511763
TI  - Hydralazine dilates large epicardial coronary arteries in conscious dogs through
      an endothelium-independent mechanism.
AB  - In chronically instrumented conscious dogs, hydralazine (30-300 micrograms/kg)
      and nitroglycerin (NTG 0.03-10 micrograms/kg) dose-dependently dilated large
      epicardial coronary arteries. Simultaneously, hydralazine also dose-dependently
      dilated small coronary arteries, whereas a similar effect was observed only after
      NTG > 0.3 microgram/kg. When large coronary arteries were deendothelialized by a
      balloon angioplasty catheter, dilation of large coronary arteries in response to
      acetylcholine (ACh 0.3 microgram/kg) and to reactive hyperemia was reduced by 87
      and 95%, respectively. In contrast, vasodilation of large coronary arteries
      induced by hydralazine and NTG was only minimally and similarly affected (-19%
      for both drugs). These findings demonstrate that in vivo hydralazine-induced
      dilation of large coronary arteries is endothelium independent.

PMID- 7511762
TI  - Effects of enalaprilat on circadian profiles in blood pressure and heart rate of
      spontaneously and transgenic hypertensive rats.
AB  - We investigated the dose-dependent cardiovascular effects of enalaprilat at
      different dosing times in two animal models of hypertension. Blood pressure (BP)
      and heart rate (HR) were measured telemetrically in 5 spontaneously hypertensive
      rats (SHR) and in 5 transgenic hypertensive rats (TGR) after intraperitoneal
      (i.p.) injection of enalaprilat either at 700 h or at 1900 h. In SHR, dosing of
      enalaprilat at the beginning of the resting period, i.e., at 700 h, significantly
      reduced BP but did not influence HR. After dosing at 1900 h, BP was unchanged,
      whereas HR increased, which might have resulted from reflexly increased
      sympathetic tone. In TGR, enalaprilat at either dosing time decreased BP dose
      dependently and to a higher extent than in SHR, but the effects were more
      pronounced after morning than after evening dosing. These findings demonstrate
      that in two animal models of hypertension the antihypertensive effects of
      enalaprilat depended on the time of drug dosing.

PMID- 7511764
TI  - Endogenous nitric oxide modulates vasopressor responses, but not depressor
      responses, to spinal sympathetic nerve stimulation in pithed rats.
AB  - The effects of N omega-nitro-L-arginine methylester (L-NAME), an inhibitor of
      nitric oxide (NO) synthase (1,5, and 10 mg/kg) on vasopressor and depressor
      responses to segmental sympathetic nerve stimulation were studied in the pithed
      rat preparation. Vasopressor responses were evoked by stimulation of the spinal
      sympathetic outflow at T6-T8 (30 V, 0.05 ms at 5 Hz with 10 pulses). This pressor
      response was biphasic: An initial transient response (to nerve stimulation) was
      followed by a later prolonged response (to adrenal catecholamine release). L-NAME
      1, 5, and 10 mg/kg increased mean arterial blood pressure (MAP); this effect was
      maximal at 1 mg/kg L-NAME, but had no effect on heart rate (HR). L-NAME 1, 5, and
      10 mg/kg potentiated both phases of the pressor response; the effect was maximal
      at 10 mg/kg. Vasodepressor responses were evoked by stimulation of the spinal
      sympathetic outflow at S2-L6 (30 V, 0.05 ms at 5 Hz with 10 pulses). L-NAME 1, 5,
      and 10 mg/kg did not inhibit these depressor responses. We conclude that
      inhibition of the synthesis of endogenous NO causes a hypertension in pithed rats
      that is associated with increased vasoconstriction in response to sympathetic
      nerve stimulation and adrenal catecholamine release. Systemic vascular depressor
      responses to segmental sympathetic nerve stimulation are not affected, however;
      therefore, NO cannot be the major mediator of these responses.

PMID- 7511765
TI  - Changes in the endothelial cyclooxygenase pathway in resistance arteries of
      spontaneously hypertensive rats.
AB  - Vasodilator responses to adenosine and acetylcholine (ACh) were studied in ring
      preparations of mesenteric resistance arteries of Wistar-Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR). Adenosine (10(-7)-3 x 10(-4) M) caused
      relaxations in rings with endothelium. The relaxation was more pronounced in WKY
      than in SHR. Removal of the endothelium in WKY, but not in SHR, reduced the
      relaxation. In rings without endothelium, the relaxation was identical in the two
      strains. In WKY, the cyclooxygenase inhibitor meclofenamic acid attenuated the
      relaxation to adenosine in rings with endothelium but not in rings without
      endothelium. With meclofenamic acid, the relaxation was identical in WKY arteries
      with and without endothelium. ACh (10(-9)-10(-4) M) evoked endothelium-dependent
      relaxations in WKY. In contrast, in SHR the muscarinic agonist evoked
      contractions at higher concentrations (10(-6)-10(-4) M), whereas lower
      concentrations of ACh caused relaxations similar to those observed in WKY. The
      contraction in SHR was completely inhibited by meclofenamic acid, and with
      meclofenamic acid the relaxation to ACh was identical in WKY and SHR. Thus,
      adenosine evokes endothelium-dependent (through release of cyclooxygenase
      product) and endothelium-independent relaxations and ACh evokes endothelium
      dependent relaxations in rat mesenteric resistance arteries. In SHR, the
      endothelium-dependent responses to the agonists are altered owing to the changes
      in the endothelial cyclooxygenase pathway.

PMID- 7511766
TI  - Nitric oxide may participate in V2 vasopressin-receptor-mediated renal
      vasodilation.
AB  - Using pentobarbital-anesthetized euvolemic dogs, we investigated whether
      vasopressin V2-receptor stimulation induced renal vasodilation and whether nitric
      oxide (NO) had a role in the process. Intrarenal infusion of arginine-vasopressin
      (AVP) resulted in renal vasoconstriction with pressor response. After
      preadministration of a V1-receptor antagonist, however, intrarenal infusion of
      AVP caused an increase in renal blood flow (RBF) without pressor action,
      indicating renal vasodilation. This renal vasodilation was not observed when we
      infused AVP after-simultaneous pretreatment with V1- and V2-receptor antagonists.
      Even in the absence of the V2-receptor antagonist, this renal vasodilation was
      attenuated by intrarenal infusion of L-NG-nitroarginine (L-NNA). Concomitant
      infusion of L-arginine prevented the inhibitory effect of L-NNA on renal
      vasodilation induced by intrarenal infusion of AVP in the presence of the V1
      antagonist. These data indicate that the renal vasodilation caused by intrarenal
      infusion of AVP in the presence of a V1-antagonist was mediated by V2-receptor
      stimulation, and the inhibitory effect of L-NNA on V2-receptor-mediated renal
      vasodilation was attributed to its inhibitory effect on NO synthesis, suggesting
      that NO may participate in V2-receptor-mediated renal vasodilation.

PMID- 7511767
TI  - Induction of enhanced release of endothelium-derived relaxing factor after
      prolonged exposure to alpha-adrenergic agonists: role in desensitization of
      smooth muscle contraction.
AB  - Desensitization of alpha 1-adrenergic receptor-mediated contraction occurs in rat
      aorta after in vitro exposure to alpha-adrenergic agonists; we previously showed
      that a component of the desensitization is endothelial cell dependent. Our
      primary purpose was to examine possible alterations in either the release or
      action of endothelium-derived relaxing factor (EDRF) in desensitized blood
      vessels. Rings of rat aorta were desensitized in vitro by exposure to
      phenylephrine (PE) for 6 h with impaired subsequent ability of PE to induce
      smooth muscle contraction. PE also induced heterologous desensitization of
      serotonin-induced contraction, which was blocked by the alpha 1-adrenergic
      selective antagonist prazosin. Using a "sandwich" bioassay technique, we noted
      enhanced release of EDRF from the aortic rings that had been previously exposed
      to PE as compared with controls. The capacity of PE to activate accumulation of
      inositol monophosphate was impaired in the desensitized blood vessels, both with
      and without endothelium. Our results suggest that prolonged exposure to alpha
      adrenergic agonists leads to several adaptations in vascular smooth muscle (VSM),
      including enhanced release of EDRF. Although impaired action of EDRF has been
      suggested to play a role in diseases such as diabetes and atherosclerosis, our
      results indicate that release and action of EDRF may be enhanced with prolonged
      exposure to alpha-agonists.

PMID- 7511768
TI  - Endothelin ETA-receptors couple to inositol phosphate formation and inhibition of
      adenylate cyclase in human right atrium.
AB  - To study signal transduction pathways of endothelin (ET) in human heart, we
      assessed, in isolated human right atria, the effects of ET-1 and ET-3 on inositol
      phosphate (IP) formation and on the adenylate cyclase/cyclic AMP system. In right
      atrial slices, ET-1 (10(-10)-10(-6)M) concentration-dependently increased [3H]IP
      accumulation and decreased 10-microM isoprenaline-induced or 1-microM forskolin
      induced increases in cyclic AMP content. ET-3 was approximately 100 times less
      potent. The cyclic AMP-decreasing effect of ET-1 (10(-11)-10(-6)M) could also be
      demonstrated directly in adenylate cyclase assays in right atrial membranes;
      again, ET-3 was approximately 100 times less potent. We conclude that in human
      right atrium, ETA receptors couple to two different signal-transduction pathways:
      IP formation and inhibition of adenylate cyclase.

PMID- 7511769
TI  - [Multivisceral resection of advanced colorectal cancer].
AB  - From 1 September to 1 January 1990, a total of 1232 patients underwent surgery
      for colorectal cancer. Resection was performed on 1112 (90.3%) patients. It was
      curative in 917 cases and palliative in 195. Multivisceral resection was
      necessary 82 times because of tumour infiltration of adjacent organs (curative:
      69 cases; palliative: 13 cases). The complication rate (26.7% vs 27.5%) and
      mortality rate (3.4% vs 2.9%) were similar to those for curative resections
      without multivisceral extension. The 5-year survival rate was also similar in the
      two groups (58% vs 55%). These results show that curative multivisceral
      resections can lead to the same long-term results as conventional curative
      resections. These data are encouraging, and tumour infiltration of neighbouring
      organs should not be taken to demonstrate inoperability.

PMID- 7511770
TI  - [Does saving the pylorus in pancreatoduodenectomy for periampullary cancer have a
      value?].

PMID- 7511771
TI  - The relative contributions of transcription and translation to plasmid DNA
      supercoiling in Salmonella typhimurium.
AB  - Mutations affecting DNA topoisomerase I (topA) in Salmonella typhimurium were
      isolated and graded on the basis of their ability to reverse the effects of gyrB
      mutations on his operon expression. Different topA and gyrB alleles (in otherwise
      isogenic strains) were used to gather insights into the transcription-dependent
      variability of plasmid DNA-linking deficit in growing bacteria. This study showed
      that modulation of DNA supercoiling by transcription results from the action of
      two components: one is highly dependent on the coupling of translation to RNA
      chain elongation; and the other is unrelated to protein synthesis and entirely
      dependent on promoter determinants. The former greatly predominates in DNA
      topoisomerase I mutants (topA and topA gyrB) while the latter is the sole
      contributor to plasmid DNA-linking deficit in wild-type cells. Altogether, these
      data suggest that whereas translation acts by enhancing the formation of twin
      supercoiled domains during elongation, the promoter-dependent effects bear no
      relation to the twin-supercoiled-domain model and are better explained by a
      mechanism which responds to the binding/unwinding of template DNA by RNA
      polymerase.

PMID- 7511772
TI  - Growth phase and low pH affect the thermal regulation of the Yersinia
      enterocolitica inv gene.
AB  - The inv gene encodes the protein invasin, which is the primary invasion factor
      for Yersinia enterocolitica in vitro and in vivo. Previous studies of Yersinia
      species have shown that inv expression and entry into mammalian cells are
      temperature regulated. Invasin production is reduced at the host temperature of
      37 degrees C as compared to production at ambient temperature; consequently, this
      study was initiated to determine whether other host environmental signals might
      induce inv expression at 37 degrees C. An inv::phoA translational fusion was
      recombined on to the Y. enterocolitica chromosome by allelic exchange to monitor
      inv expression. Molecular characterization of expression of the wild-type inv
      gene and the inv::phoA fusion showed that invasin is not produced until early
      stationary phase in bacteria grown at 23 degrees C. Y. enterocolitica grown at 37
      degrees C and pH 5.5 showed levels of inv expression comparable to those observed
      in bacteria grown at 23 degrees C. An increase in Na+ ions caused a slight
      increase in expression at 37 degrees C. However, expression at 37 degrees C was
      unaffected by anaerobiosis, growth medium, calcium levels, or iron levels.
      Additionally, Y. enterocolitica expressed invasin in Peyer's patches two days
      after being introduced intragastrically into BALB/c mice. These results suggest
      that invasin expression in Y. enterocolitica may remain elevated early during
      interaction with the intestinal epithelium, a site at which invasin was shown to
      be necessary.

PMID- 7511773
TI  - Immunogenicity and evolutionary variability of epitopes within IgA1 protease from
      serogroup A Neisseria meningitidis.
AB  - Five murine epitopes were defined and mapped within IgA1 protease produced by
      Neisseria meningitidis. Epitopes 1 and 2 were present in IgA1 protease from all
      strains, and from Neisseria gonorrhoeae. Epitopes 3 through to 5 varied between
      subgroups of serogroup A meningococci, but have remained constant over decades
      within the subgroups, except for epitope 4, which changed between 1983 and 1987
      during the spread of subgroup III meningococci from Asia to Africa. Binding of
      monoclonal antibodies to epitopes 1, 4 and 5 neutralized enzymatic function.
      Human sera containing antibodies to IgA1 protease as a result of natural
      infection inhibited binding of monoclonal antibodies to epitope 4 but not to the
      other epitopes.

PMID- 7511775
TI  - The citrulline biosynthetic operon, argC-F, and a ribose transport operon, rbs,
      from Bacillus subtilis are negatively regulated by Spo0A.
AB  - A method is described here that can be used to identify operons whose expression
      is controlled by any particular regulator protein. This method was used to
      identify operons whose expression is negatively regulated by Spo0A in Bacillus
      subtilis. Twenty-eight strains were identified, each of which contains an operon
      lacZ transcriptional fusion, negatively regulated, either directly or indirectly,
      by Spo0A. In one of these strains (CSA8), the lacZ gene is fused to the argC-F
      operon positioned at 100 degrees on the B. subtilis chromosome. The regulated
      expression of this operon by Spo0A-P is mediated indirectly through the
      transition state regulator AbrB and is manifest only during growth on solid
      medium. In a second strain (CSA15), the lacZ gene is fused to an operon encoding
      a transport system which displays features characteristic of the ABC group of
      transporters, and which has a very high level of identity to the ribose transport
      system from Escherichia coli. Expression of the ribose transport operon is
      directed by a single SigA-type promoter. Transcription from this promoter is
      repressed by the phosphorylated form of Spo0A during the late
      exponential/transition phase of the growth cycle and this control is not mediated
      through the transition-state regulator, AbrB.

PMID- 7511774
TI  - The mutL repair gene of Escherichia coli K-12 forms a superoperon with a gene
      encoding a new cell-wall amidase.
AB  - We report a molecular genetic analysis of the region immediately upstream from
      the Escherichia coli mutL DNA repair gene at 94.8 min. An open reading frame
      ending 9 bp upstream from the start of mutL corresponds to a 48 kDa polypeptide
      detected previously in minicells. The predicted amino acid sequence of this 48
      kDa polypeptide shows homology to the major N-acetylmuramoyl-L-alanine amidase
      autolysin of Bacillus subtilis, a known amidase of Bacillus licheniformis, and
      the product of a Salmonella typhimurium gene that maps near 50 min. Insertions in
      this upstream gene, which we named amiB, or in mutL did not affect cell shape or
      viability; however, overexpression of the AmiB polypeptide caused cell lysis,
      hypersensitivity to osmotic shock and treatment with water, and temporary
      autolysis by low levels of antibiotics, which are all consistent with AmiB acting
      as a cell-wall hydrolase. Analysis of chromosomal transcription demonstrated that
      amiB forms a complex operon with mutL and two additional upstream genes. mutL
      transcripts also originated from an internal promoter, designated PmutL, located
      in amiB 312 bp upstream from the translational start of mutL. Together, these
      results suggest that E. coli contains a second amidase possibly involved in cell
      wall hydrolysis, septation, or recycling, and that transcription of this amidase
      is directly linked to a gene central for DNA repair.

PMID- 7511776
TI  - TRH: mediator of prolactin in the prostate?
AB  - Thanks to our preoccupation with androgen ablative therapy, no significant
      progress has been made in combating prostate cancer (PCa) in 50 years. Also,
      there have been only limited advances in medical treatment of benign prostatic
      hyperplasia (BPH). The intent of this essay is to explore the mode of
      participation of prolactin (Prl) in prostatic physiology in the hope that such
      knowledge will reveal new avenues through which both BPH and PCa can be opposed
      even prevented. An especially novel aspect of this study is the recognition of
      the presence and androgen- and prolactin-dependent concentration of the
      tripeptide, thyrotropin-releasing hormone (TRH) in prostatic tissue. It is
      hypothesized that, whereas TRH is the hypothalamic stimulus of hypophyseal Prl
      secretion, it may, in the prostate, serve as the mediator of Prl's independent
      and androgen-dependent controls of the gland's growth and function. Through an
      overview of these relationships, methods are suggested both for their study and
      for their adaptation to early detection and prevention of imminent pathogenesis.

PMID- 7511778
TI  - Human metallothionein isoform gene expression in cisplatin-sensitive and
      resistant cells.
AB  - Overexpression of metallothioneins (MTs) has been observed in some cis
      diamminedichloroplatinum (CDDP)-resistant cells. We have developed
      oligonucleotide probes for each of the six non-neuronal human MT (hMT) isoforms
      and used them to assay hMT isoform expression in three pairs of CDDP-resistant
      and -sensitive human carcinoma cell lines, i.e., SCC25/CP versus SCC25 cells,
      H69/CP versus H69 cells, and SW2/CP versus SW2 cells. We found a 9-fold increase
      in basal hMT-IIa mRNA levels and a 5-fold increase in hMT-le mRNA levels in
      SCC25/CP cells, compared with SCC25 cells. Nuclear run-on studies also revealed a
      3-fold increase in hMT-IIa transcription rate. Basal hMT-IIa steady state mRNA
      levels were 2-3.6-fold greater in H69/CP and SW2/CP cells, compared with their
      parental cells. No significant basal expression of hMT-Ia, -Ib, -If, or Ig was
      detected in any cells, suggesting that overexpression of these isoforms was not
      commonly associated with the CDDP-resistant phenotype. Levels of constitutively
      expressed hMT isoforms, as well as hMT-If, could be elevated by treatment of all
      cells with 100 microM zinc. The universal overexpression of hMT-IIa suggests a
      role of this particular isoform in CDDP resistance. Using our isoform-specific
      hMT-IIa probe and the demethylating agent 5'-azacytidine (AZC), we found that AZC
      pretreatment increased basal hMT-IIa mRNA levels in SCC25 but not SCC25/CP cells,
      suggesting that DNA hypomethylation was responsible for higher basal hMT-IIa mRNA
      levels in SCC25/CP cells. AZC had little or no effect on hMT-If or -Ig
      expression. Limited restriction analysis by methylation-sensitive enzymes,
      however, revealed no obvious differences in the methylation status of the hMT-IIa
      promoter in either SCC25 or SCC25/CP cells.

PMID- 7511777
TI  - Risperidone for chronic schizophrenia.

PMID- 7511779
TI  - Coordinate induction of glutathione S-transferase alpha, mu, and pi expression in
      murine liver after a single administration of oltipraz.
AB  - The antischistosomal agent oltipraz displays a unique ability to inhibit
      chemically induced carcinogenesis in a variety of animal models. Its apparent
      lack of carcinogen specificity and low toxicity make it an attractive candidate
      for further development as a chemopreventive agent. The mechanism by which
      oltipraz affords cellular protection is thought to involve the modulation of
      phase II detoxication enzymes. The present study examines the regulation of each
      class of glutathione S-transferase (EC 2.5.1.18) in mice after a single oral
      administration of oltipraz. Glutathione S-transferase activity in the liver
      increased in a dose-dependent manner after drug exposure. Oltipraz administration
      (1 g/kg, by gavage) elevated glutathione S-transferase activity to a maximum (4.5
      fold) on day 4 after treatment. Western blot analyses demonstrated the induction
      of all three classes of glutathione S-transferase (alpha, mu, and pi) by
      oltipraz. Our murine studies suggest that the chemopreventive activity of
      oltipraz may be due in part to its ability to elevate glutathione S-transferase
      mu activity. Consistent with this possibility, associations between the
      glutathione S-transferase-mu-null phenotype and increased risk for lung, larynx,
      and bladder cancer have been recently demonstrated in humans. Coordinate
      elevations in enzymatic activity were preceded by significant elevations in
      glutathione S-transferase alpha, mu, and pi RNA on day 2 after treatment.
      Although nuclear run-on assays confirmed the transcriptional induction of all
      three classes, the maintenance of elevations in enzymatic activity after RNA
      levels returned to base-line suggests that additional mechanisms are required to
      regulate glutathione S-transferase expression. Preclinical findings are presented
      that characterize the response of each class of glutathione S-transferase to
      oltipraz exposure and support the use of these enzymes as intermediate markers of
      the chemopreventive activity of oltipraz.

PMID- 7511780
TI  - Two distinct ATP signaling mechanisms in differentiated neuroblastoma x glioma
      hybrid NG108-15 cells.
AB  - The ATP signaling mechanism in neuroblastoma x glioma hybrid NG108-15 cells
      differentiated by exposure to dibutyryl-cAMP was characterized. In cells loaded
      with fura-2, ATP rapidly raised the cytosolic Ca2+ concentration ([Ca2+]i); the
      magnitude of the rise was inversely proportional to the extracellular Na+
      concentration. Large increases in cytosolic Na+ concentration, measured with the
      fluorescent Na+ indicator sodium-binding benzofuran isophthalate, were dose
      dependently elicited by ATP. ATP also evoked the entry of ethidium bromide into
      cells, and this process was inhibited by Mg2+. Inositol-1,4,5-trisphosphate (IP3)
      generation induced by ATP was totally blocked by removal of extracellular Ca2+,
      but residual IP3 generation still remained in nondifferentiated cells. In
      addition, ATP produced a concentration-, time-, and Mg(2+)-dependent biphasic
      uptake of 45Ca2+. A range of nucleotides and ATP analogues, including CTP, UTP,
      and GTP, induced only 9-29% of the ATP response. However, adenosine 5'
      thiotriphosphate evoked 79% of ATP-induced 45Ca2+ uptake. 45Ca2+ uptake elicited
      by ATP could be potently blocked by purinoceptor antagonists, but other tested
      reagents less effectively blocked the action of ATP. When bradykinin was used as
      an agonist, the [Ca2+]i rise was transient and was insensitive to the
      extracellular Na+ concentration. Na+ influx, entry of ethidium bromide, and
      45Ca2+ uptake were unaffected by bradykinin. Furthermore, bradykinin-evoked IP3
      generation was insensitive to extracellular Ca2+. Neither ATP nor bradykinin had
      any effect on cAMP levels within cells. These data suggest that ATP induces a
      [Ca2+]i rise in differentiated NG108-15 cells via two distinct Ca2+ influx
      mechanisms, i.e., a receptor-operated cation channel and pores formed by ATP4-.
      These mechanisms are distinct from those elicited by bradykinin.

PMID- 7511781
TI  - N-methyl-D-aspartate receptors: different subunit requirements for binding of
      glutamate antagonists, glycine antagonists, and channel-blocking agents.
AB  - Expression of the NR-1 subunit in Xenopus oocytes produces channels that respond
      to glutamate and are blocked by competitive and noncompetitive antagonists of the
      N-methyl-D-aspartate (NMDA) receptor. Ionic conductances through these channels
      are increased by coexpression with NR-2 receptor subunits. We have characterized
      the pharmacological properties of NMDA receptors assembled from combinations of
      subunits expressed in transfected cells, to determine the minimum subunit
      requirements for binding of competitive glutamate antagonists, glycine
      antagonists, and channel-blocking agents, as detected by ligand-binding
      experiments. Expression of NR-1a alone produced glycine antagonist binding,
      whereas the combination of NR-1a and NR-2A was needed to produce binding sites
      for glutamate antagonists and channel-blocking agents. These results suggest that
      functional NMDA receptors assemble from these subunits. However, differences in
      the pharmacological effects of NMDA and polyamines show that not all
      characteristics of native NMDA receptors are reproduced by this combination of
      subunits.

PMID- 7511782
TI  - [Derivatives of ddUTP, modified at the 5-position of uridine, as substrate
      terminators of reverse transcriptase. Hydrolysis of oligonucleotides, terminated
      by these analogs, by phosphodiesterase I].
AB  - Synthesis of 2',3'-dideoxyuridine 5'-triphosphate analogues with fluorescent and
      biotin residues at C5 of uracil base was carried out. The substrate properties of
      these analogues were studied with AMV, M-MLV, and HIV reverse transcriptase. All
      5-derivatives studied were shown to be incorporated into the 3'-terminus of
      oligonucleotide. The stability of oligodeoxyribonucleotides terminated with ddUTP
      analogues modified at the 5-position of the pyrimidine residue to the exonuclease
      action of phosphodiesterase I and Klenow enzyme was more than 1000 times higher
      than that of nonterminated oligonucleotides.

PMID- 7511783
TI  - [Modified nucleoside-5'-triphosphates with an additional conjugated through the
      2'-3'-fused ring as DNA polymerase substrates].
AB  - 5'-Triphosphates of 1-(2',3'-epithio-2',3'-dideoxy-beta-D-lyxofuranosyl) thymine,
      1-(2',3'-epithio-2',3'-dideoxy-beta-D-ribofuranosyl) thymine and 2',3'
      lyxoanhydrothymidine have been shown to be terminator substrates of human
      immunodeficiency virus and avian myeloblastosis virus reverse transcriptases as
      well as DNA polymerase I from E. coli. At the same time they do not terminate DNA
      synthesis catalysed by DNA polymerase epsilon from human placenta. The KM values
      of ltTTP, rtTTP and laTTP incorporation into DNA chain agree closely with each
      other, being 1.5-2.5 times higher than KM for dTTP. Furthermore, Vmax values for
      modified substrates are only 2-3 times less than Vmax for dTTP. The evidence
      favours the hypothesis of a great affinity of modified nucleosides with flattened
      ribose ring of glycone for DNA polymerases active sites.

PMID- 7511784
TI  - [Resistance to azidothymidine in human immunodeficiency virus (HIV) infection].
AB  - The phenomenon of resistance to azidothymidine during the infection of human
      immunodeficiency virus (HIV) is reviewed. Different aspects of AZT resistance,
      including biological and virological characteristics of resistant HIV isolates,
      genetical mechanisms of resistance, cross-resistance to other nucleoside analogs
      and non-nucleoside inhibitors, are analyzed. The role of target cells in AZT
      resistance is also discussed.

PMID- 7511785
TI  - Regulation of the 5'-flanking region of the mouse androgen receptor gene by cAMP
      and androgen.
AB  - Both androgens and cAMP-mediated hormones are known to regulate expression of the
      androgen receptor (AR) gene. In order to determine whether these effects occur at
      the transcriptional level, transfection studies were conducted with a 1.5
      kilobase fragment of the 5'-flanking region of the mouse AR gene coupled to a
      chloramphenicol acetyltransferase (CAT) reporter gene. We demonstrated that the
      cAMP pathway regulates expression of the mouse AR (mAR) 5'-CAT construct in mouse
      pituitary (alpha T3-1), rat pituitary (GC), and quail fibroblast (QT6) cell
      lines. Deletional analysis indicated that several areas of this clone, including
      a region containing a putative cAMP response element (CRE), are involved in
      mediating cAMP regulation of the AR gene. Oligonucleotides containing a putative
      CRE, linked to the thymidine kinase promoter of pBLCAT2, conferred increased
      forskolin induction of CAT activity. Furthermore, overexpression of a CRE binding
      protein up-regulated expression of the mAR 5'-CAT constructs. Bandshift data
      demonstrated that the putative CRE forms specific, competable complexes with
      nuclear proteins from alpha T3-1 and QT6 cells. Additional experiments indicated
      that AR can modulate both basal and forskolin-induced CAT activity in an androgen
      dependent fashion. These data provide evidence that the 5'-flanking region of the
      mAR gene contains sequences which mediate the effects of both cAMP and androgens.

PMID- 7511787
TI  - Coordinate control of the alpha- and beta-subunit genes of human chorionic
      gonadotropin by trophoblast-specific element-binding protein.
AB  - The alpha- and beta-subunit genes of hCG are coordinately regulated in the
      trophectoderm of the early embryo and placenta. Placenta-specific expression of
      the alpha-subunit gene is determined by a composite enhancer made of three
      clustered components: cAMP-responsive elements, a GATA site, and the trophoblast
      specific element (TSE). We have investigated the basis of placenta-specific
      expression of the major hCG beta-subunit gene, hCG beta 5. Enhancement of
      expression localizes to the region from -305 to -279, whereas full cAMP
      regulation requires the region from -305 to -249. Four DNAse-I footprints are
      present, three of which can be competed by the TSE element from the alpha-subunit
      gene. Methylation interference establishes that binding to the element located in
      the key region for expression, from -301 to -275, requires contacts with a
      CCNNNGGG core sequence that matches the alpha-subunit gene TSE. Sequence-specific
      DNA affinity chromatography using the alpha-subunit gene TSE allows purification
      of TSE-binding protein. This purified protein binds specifically to the key
      element, -301 to -275, and to at least two additional TSE elements clustered in
      the regulatory region of the hCG beta 5 gene. We conclude that both the alpha-
      and beta-subunit genes of hCG require the placenta-specific factor TSE-binding
      protein for expression, providing a mechanism for their coordinate regulation in
      placental cells.

PMID- 7511786
TI  - Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding protein 1 gene
      transcription by hormones and provision of amino acids in rat hepatocytes.
AB  - Synthesis of insulin-like growth factor-I (IGF-I) and IGF binding protein-1
      (IGFBP-1) is altered in diabetes and malnutrition, but underlying processes are
      poorly understood. To study molecular mechanisms, we examined regulation of IGF-I
      and IGFBP-1 gene transcription in primary cultures of rat hepatocytes.
      Transcription of the IGF-I and IGFBP-1 genes was measured as incorporation of
      [alpha-32P]UTP into preinitiated message in isolated nuclei. IGFBP-1 gene
      transcription was not sensitive to reduction in amino acid concentration from 5x
      to 0.5x rat arterial plasma levels. However, IGF-I gene transcription fell 60-70%
      in response to reduced provision of amino acids. Culture with 10(-9) M insulin
      lowered IGFBP-1 gene transcription 50% below control levels (10-11 M) but did not
      affect IGF-I gene transcription; 10(-6) M insulin raised IGF-I gene transcription
      2-fold. After an acute reduction in insulin concentration, IGFBP-1 transcription
      began to rise within 30 min, but IGF-I gene transcription was unchanged over 120
      min. Similarly, 3-6 h were required for stimulation of IGF-I gene transcription
      by insulin, but a 40% decrease in IGFBP-1 gene transcription could be detected
      within 15 min after adding 10(-6) M insulin, and suppression of IGFBP-1
      transcription by insulin was unaffected by the presence of cycloheximide. Effects
      of insulin on IGFBP-1 gene transcription were not mimicked or antagonized by
      phorbol ester.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511788
TI  - Direct monitoring as well as sensitive diagnosis of Pneumocystis carinii
      pneumonia by the polymerase chain reaction on sputum samples.
AB  - In order to evaluate the usefulness of the polymerase chain reaction (PCR) for
      diagnosis and monitoring of Pneumocystis carinii pneumonia (PCP) in specimens
      obtained from non-invasive techniques, expectorated or induced sputa were
      collected from 30 patients who were tentatively diagnosed as having PCP and
      administered intravenous trimethoprim-sulfamethoxazole. Using appropriate
      criteria, 13 of these cases were diagnosed as having PCP, 12 cases were diagnosed
      of other pulmonary diseases, and five cases were omitted from the study according
      to the exclusion criteria. PCR was performed using primers based on the P.
      carinii 5S rRNA sequence. Pneumocystis carinii was detected in nine of the 13
      defined cases (sensitivity of 69%) and in none of 12 non-PCP cases (specificity
      of 100%). In contrast, P. carinii was detected in only one case by microscopic
      examination using Diff-Quik stain. Therefore, the sensitivity of PCR was
      significantly higher than that observed with the stain (P < 0.05, chi 2 = 6.125).
      Sputum samples were also obtained from eight cases during the treatment. The
      eradication of P. carinii from the sputum as judged by PCR varied from three to
      38 days (median 6.5 days) after the start of the treatment. Pneumocystis carinii
      shedding in sputum correlated with the time between initial clinical symptoms and
      initiation of the treatment (P < 0.05, r = 0.810), but not with the tension of
      PaO2 at the time of diagnosis. This preliminary study demonstrates that PCR
      allows early diagnosis of PCR and that close monitoring with non-invasive
      specimens can be performed by PCR.

PMID- 7511789
TI  - Molecular identification of cardioviruses by enzymatic amplification.
AB  - Cardiovirus specific sequences located in the 5' NTR are used to amplify viral
      RNA by PCR. General primers were selected for the amplification of cardioviruses,
      including encephalomyocarditis virus (EMCV), mengovirus and Theiler's murine
      encephalomyelitis virus (TMEV. Additionally, ECHO virus type 22, an atypical
      enterovirus, could also be detected with the general cardiovirus primers. An
      internal encephalomyocarditis virus specific probe and a general cardiovirus
      probe are used to discriminate EMCV from other cardioviruses. The sensitivity of
      the PCR was determined at 10 pfu after hybridization with an internal
      oligonucleotide probe. Specificity was tested with a broad range of
      picornaviruses and other nonrelated RNA and DNA viruses. The applicability of the
      assay was demonstrated by the detection of TMEV RNA in tissue samples from
      experimentally-infected mice.

PMID- 7511790
TI  - Development and evaluation of the polymerase chain reaction method for diagnosis
      of Mycoplasma gallisepticum infection in chickens.
AB  - A polymerase chain reaction (PCR) method specific for Mycoplasma gallisepticum
      (MG) was evaluated. The PCR method was found to detect as few as two colour
      changing units (CCU) of MG and did not give false positive reactions with other
      avian mycoplasmas. In chickens inoculated with either MG or Mycoplasma synoviae
      (MS), the PCR method was found to closely correlate with MG culture reisolation
      methods in chicken intranasally inoculated with MG. All chickens inoculated with
      MS tested negative using the MG PCR method.

PMID- 7511791
TI  - Ethylene thiourea (ETU). A review of the genetic toxicity studies.
AB  - Ethylene thiourea (ETU) is a common contaminant, metabolite and degradation
      product of the fungicide class of ethylene bisdithiocarbamates (EBDCs); as such,
      they present possible exposure and toxicological concerns to exposed individuals.
      ETU has been assayed in many different tests to assess genotoxicity activity.
      While a great number of negative results are found in the data base, there is
      evidence that demonstrates ETU is capable of inducing genotoxic endpoints. These
      include responses for gene mutations (e.g. Salmonella), structural chromosomal
      alterations (e.g. aberrations in cultured mammalian cells as well as a dominant
      lethal assay) and other genotoxic effects (e.g. bacterial rec assay and several
      yeast assays). It is important to consider the magnitude of the positive
      responses as well as the concentrations/doses used when assessing the
      genotoxicity of ETU. While ETU induces a variety of genotoxic endpoints, it does
      not appear to be a potent genotoxic agent. For example, it is a weak bacterial
      mutagen in the Salmonella assay without activation in strain TA1535 at
      concentrations generally above 1000 micrograms/plate. Weak genotoxic activity of
      this sort is usually observed in most of the assays with positive results. Since
      ETU does not appear very potent and is not extremely toxic to test cells and
      organisms, it is not surprising to find that ETU does not produce consistent
      effects in many of the assays reviewed. Consequently, in many instances, mixed
      results for the same assay type are reported by different investigators, but as
      reviewed herein, these results may be dependent upon the test conditions in each
      individual laboratory. A primary shortcoming with many of the reported negative
      results is that the concentrations or doses used are not high enough for an
      adequate test for ETU activity. There are also problems with many of the negative
      assays generally in protocol or reporting, particularly with the in vivo studies
      (e.g. inappropriate sample number and/or sampling times; inadequate top dose
      employed). Overall, while ETU does not appear to be a potent genotoxic agent, it
      is capable of producing genotoxic effects (e.g. gene mutations, structural
      chromosomal aberrations). This provides a basis for weak genotoxic activity by
      ETU. Furthermore, based on a suggestive dominant lethal positive result, there
      may be a concern for heritable effects. Due to the many problems with the conduct
      and assessment of the in vivo assays, it is worth repeating in vivo cytogenetic
      assays and a dominant lethal assay (with acceptable test procedures and data
      generation) to determine if these results would continue to support a heritable
      mutagenicity concern.

PMID- 7511792
TI  - An assessment of the genetic toxicity of atrazine: relevance to human health and
      environmental effects.
AB  - The genetic toxicity of atrazine, a member of the s-triazine herbicides, was
      reviewed with the objective of classifying the chemical. Atrazine has been
      subjected to a broad range of genetic tests with predominantly negative results.
      Some publications, specifically those measuring dominant lethality in mice and
      bone marrow clastogenicity in rodents, reported conflicting results across two or
      more independent tests. Two approaches were employed to evaluate and interpret
      the results. The first approach attempts to classify each type of genetic
      endpoint as positive or negative and resolve test conflicts by critical
      assessment of the study and detailed data. This is the more traditional "expert
      judgement" approach to hazard assessment. The second approach employs a computer
      assisted weight-of-evidence method of data analysis. This approach does not
      require resolution of conflicts but uses all data sets to arrive at a
      classification of hazard. The first approach was able to resolve some conflicts
      but not all. Use of the "expert judgement" results in an equivocal conclusion and
      classification. Use of the weight-of-evidence method resulted in a conclusion
      that atrazine does not pose a mutagenic hazard. The weight-of-evidence scheme is
      proposed to be a more practical and relevant approach for assessing complex data
      sets.

PMID- 7511793
TI  - Potential genotoxic, mutagenic and antimutagenic effects of coffee: a review.
AB  - Coffee and caffeine are mutagenic to bacteria and fungi, and in high
      concentrations they are also mutagenic to mammalian cells in culture. However,
      the mutagenic effects of coffee disappear when bacteria or mammalian cells are
      cultured in the presence of liver extracts which contain detoxifying enzymes. In
      vivo, coffee and caffeine are devoid of mutagenic effects. Coffee and caffeine
      are able to interact with many other mutagens and their effects are synergistic
      with X-rays, ultraviolet light and some chemical agents. Caffeine seems to
      potentiate rather than to induce chromosomal aberrations and also to transform
      sublethal damage of mutagenic agents into lethal damage. Conversely, coffee and
      caffeine are also able to inhibit the mutagenic effects of numerous chemicals.
      These antimutagenic effects depend on the time of administration of coffee as
      compared to the acting time of the mutagenic agent. In that case, caffeine seems
      to be able to restore the normal cycle of mitosis and phosphorylation in
      irradiated cells. Finally, the potential genotoxic and mutagenic effects of the
      most important constituents of coffee are reviewed. Mutagenicity of caffeine is
      mainly attributed to chemically reactive components such as aliphatic
      dicarbonyls. The latter compounds, formed during the roasting process, are
      mutagenic to bacteria but less to mammalian cells. Hydrogen peroxide is not very
      active but seems to considerably enhance mutagenic properties of methylglyoxal.
      Phenolic compounds are not mutagenic but rather anticarcinogenic. Benzopyrene and
      mutagens formed during pyrolysis are not mutagenic whereas roasting of coffee
      beans at high temperature generates mutagenic heterocyclic amines. In conclusion,
      the mutagenic potential of coffee and caffeine has been demonstrated in lower
      organisms, but usually at doses several orders of magnitude greater than the
      estimated lethal dose for caffeine in humans. Therefore, the chances of coffee
      and caffeine consumption in moderate to normal amounts to induce mutagenic
      effects in humans are almost nonexistent.

PMID- 7511794
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Cyclosporine A: review of genotoxicity and potential for adverse
      human reproductive and developmental effects. Report of a Working Group on the
      genotoxicity of cyclosporine A, August 18, 1993.
AB  - Cyclosporine is an important therapeutic agent for transplant recipients and for
      a growing number of autoimmune diseases. Experimental animal and human data has
      indicated that cyclosporine is unlikely to be genotoxic. In contrast,
      azathioprine, an agent often given with cyclosporine, is considered to be
      genotoxic making the assessment of the independent effects of cyclosporine
      difficult. Cyclosporine does appear to be related to the development of tumors,
      primarily lymphomas, in animals and humans, but the basis of its potential
      carcinogenicity is not completely understood. In terms of reproductive and
      developmental toxicity, cyclosporine produces some adverse effects in both
      experimental animals and humans. In animals, the effects are seen at high doses
      sufficient to cause maternal toxicity. In humans, outcomes such as growth
      retardation have been noted, but the confounding effects of renal toxicity and
      resultant pregnancy complications cloud the interpretation. An increase in
      congenital anomalies and genetic disease have not been found reported in human
      studies that are limited in sample size. Given that the present data indicate the
      lack of genotoxicity, a mutation epidemiology study of cyclosporine is not
      recommended. As indicated above, such a study is probably impractical for many
      genetic endpoints of interest. However, well-conducted, large multicenter studies
      of transplant patients and their offspring would allow for routine monitoring of
      an increased risk for some reproductive and developmental (possibly non-genetic)
      endpoints that are of public health importance.

PMID- 7511795
TI  - Experimental databases on inhibition of the bacterial mutagenicity of 4
      nitroquinoline 1-oxide and cigarette smoke.
AB  - Two antimutagenicity databases were prepared by applying a co-treatment procedure
      to the Salmonella reversion assay. Ninety compounds belonging to various chemical
      classes were quantitatively tested for antimutagenicity towards the direct-acting
      mutagen 4-nitroquinoline 1-oxide (4NQO) in strain TA100 of S. typhimurium and 63
      of them were additionally tested for antimutagenicity towards unfractionated
      mainstream cigarette smoke (CS) in strain TA98, in the presence of S9 mix. Twelve
      compounds (13.3%) inhibited 4NQO mutagenicity by at least 50%, with a MID50 (dose
      inhibiting 50% of mutagenicity) varying over a 1226-fold range. Twenty-six
      compounds (41.3%) inhibited CS mutagenicity, with a MID50 varying over a 520-fold
      range. Three compounds only, i.e., bilirubin, curcumin and myricetin, were
      capable of inhibiting the mutagenicities of both 4NQO and CS. However, myricetin
      and the other flavonoid rutin were at the same time mutagenic by inducing
      frameshift mutations following metabolic activation. There was a rather rigorous
      selectivity of antimutagenicity data depending on the chemical class of
      inhibitors and it was possible to discriminate protective effects within several
      pairs or series of structurally related compounds. For instance, all eight thiols
      and aminothiols inhibited 4NQO mutagenicity, which contrasted with the inactivity
      of the remaining 17 sulfur compounds tested, all of them lacking a free
      sulfhydryl group. The mutagenicity of CS was consistently inhibited by the
      majority of phenols (eight out of 10 tested) and by all two isothiocyanates, two
      dithiocarbamates, three indole derivatives, three tetrapyrrole compounds and
      three flavonoids tested. Although the results obtained cannot be extrapolated to
      other mutagens or test systems, they may provide a useful source of information
      for research in the area of antimutagenesis and for the development of
      chemopreventive agents.

PMID- 7511796
TI  - Clinical light damage by indirect ophthalmoscopy.

PMID- 7511797
TI  - Angiogenic activity of enzymes.

PMID- 7511798
TI  - The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and
      suppresses tumour growth.
AB  - The formation of new blood vessels (angiogenesis) is critical for the growth of
      tumours and is a dominant feature in various angiogenic diseases such as diabetic
      retinopathy, arthritis, haemangiomas and psoriasis. Recognition of the potential
      therapeutic benefits of controlling pathological angiogenesis has led to a search
      for angiogenesis inhibitors. Here we report that 2-methoxyoestradiol, an
      endogenous oestrogen metabolite of previously unknown function, is a potent
      inhibitor of endothelial cell proliferation and migration as well as angiogenesis
      in vitro. Moreover, when administered orally in mice, it strongly inhibits the
      neovascularization of solid tumors and suppresses their growth. Unlike the
      angiostatic steroids of corticoid structure, it does not require the co
      administration of heparin or sulphated cyclodextrins for activity. Thus, 2
      methoxyoestradiol is the first steroid to have high antiangiogenic activity by
      itself. Our results suggest that this compound may have therapeutic potential in
      cancer and other angiogenic diseases.

PMID- 7511799
TI  - A large-conductance mechanosensitive channel in E. coli encoded by mscL alone.
AB  - All cellular organisms respond to vibration, touch, gravity or changes in
      osmolarity, although the molecules on which such mechanosensations depend are
      unknown. Candidates include certain channels that gate in response to membrane
      stretch. Patch-clamp experiments with Escherichia coli envelope have revealed a
      mechanosensitive channel with very large conductance (MscL) and one with a
      smaller conductance (MscS) which may be important in osmoregulation. Here we have
      solubilized and fractionated the envelope, reconstituted the MscL activity in
      vitro, and traced it to a small protein, whose gene, mscL, we then cloned.
      Insertional disruption of mscL removes the channel activity, whereas re
      expression of mscL borne on an expression plasmid restores it. MscL-channel
      activities were observed in material from a cell-free expression system with mscL
      as the only template. The mscL nucleotide sequence predicts a unique protein of
      only 136 amino acids, with a highly hydrophobic core and very different from
      porins or other known proteins.

PMID- 7511800
TI  - Histamine-evoked Ca2+ oscillations in HeLa cells are sensitive to methylxanthines
      but insensitive to ryanodine.
AB  - The relative contribution of inositol-trisphosphate(InsP3)-sensitive and InsP3
      insensitive Ca2+ stores to the agonist-evoked oscillatory release of Ca2+ in HeLa
      cells was investigated using fura-2 cytosolic Ca2+ measurements and whole-cell
      recordings of Ca(2+)-activated K+ currents [K(Ca2+)]. The experimental approach
      chosen consisted in studying the effects on Ca2+ oscillations of a variety of
      pharmacological agents such as ryanodine, ruthenium red, caffeine and
      theophylline, which are known to affect the Ca2+ channels responsible for Ca(2+)
      induced Ca2+ release (CICR) in excitable cells. The results obtained essentially
      indicate (a) that neither ryanodine nor ruthenium red affects the generation of
      periodic K(Ca2+) current pulses in whole-cell experiments, and (b) that histamine
      induced Ca2+ oscillations are inhibited by caffeine and theophylline in a dose
      dependent manner. However, these methylxanthines were unable, at concentrations
      ranging from 0.1 mM to 10 mM, either to mobilize Ca2+ from internal stores or to
      block the initial Ca2+ rise evoked by histamine. In addition, both
      methylxanthines showed at high concentrations (10-20 mM) a moderate inhibitory
      action on the production of InsP3 induced by histamine. This effect was not
      essential to the action of caffeine on the oscillatory release of Ca2+, since an
      inhibition by caffeine of InsP3-induced Ca2+ oscillations was still observed in
      whole-cell experiments where the InsP3 concentration was kept constant. The
      results also show (c) that the application of either caffeine or theophylline
      during histamine stimulation leads systematically to an increased Ca2+
      sequestration in InsP3-sensitive Ca2+ pools, the effect observed with
      theophylline being stronger than that resulting from the application of caffeine,
      and finally (d) that the action of caffeine and theophylline is not related to an
      increase in cAMP concentration since neither forskolin (10-50 microM) nor 8-Br
      cAMP (1 mM) caused an inhibition of the InsP3-induced Ca2+ oscillations. It is
      concluded on the basis of these results that the agonist-evoked Ca2+ oscillations
      in HeLa cells do not involve directly or indirectly a ryanodine-sensitive Ca(2+)
      release channel with CICR properties, but rather arise from a control by Ca2+ of
      the InsP3 Ca(2+)-release process.

PMID- 7511801
TI  - High selectivity of the i(f) channel to Na+ and K+ in rabbit isolated sinoatrial
      node cells.
AB  - The ionic selectivity of the hyperpolarization-activated inward current (i(f))
      channel to monovalent cations was investigated in single isolated sinoatrial node
      cells of the rabbit using the whole-cell patch-clamp technique. With a 140 mM K+
      pipette, replacement of 90% external Na+ by Li+ caused a -24.5 mV shift of the
      fully activated current/voltage I/V curve without a significant decrease of the
      slope conductance. With a 140 mM Cs+ pipette, the i(f) current decreased almost
      proportionally to the decrease in external [Na+]o as Li+ was substituted. These
      responses are practically the same as those observed with N-methyl glucamine
      (NMG+) substitution, suggesting that the relative permeability of Li+ compared
      with Na+ for the i(f) channel is as low as that of NMG+. When Cs+ or Rb+ was
      substituted for internal K+, the fully activated I/V relationship for i(f) showed
      strong inward rectification with a positive reversal potential, indicating low
      permeability of the i(f) channel for Cs+ and Rb+. These results show that the
      i(f) channel is highly selective for Na+ and K+ and will not pass the similar
      ions Li+ and Rb+. Such a high degree of selectivity is unique and may imply that
      the structure of the i(f) channel differs greatly from that of other Na+ and K+
      conducting channels.

PMID- 7511802
TI  - Regulation of DU145 human prostate cancer cell proliferation by insulin-like
      growth factors and its interaction with the epidermal growth factor autocrine
      loop.
AB  - The DU145 human prostate cancer cell line was shown to possess type I insulin
      like growth factor receptors (IGFR). The addition of either IGF-I or IGF-II, but
      not insulin, to serum-free culture medium increases the rate of thymidine
      incorporation by the cells, a response which is suppressed by specific blockade
      of the previously described epidermal growth factor (EGF) autocrine growth
      regulatory loop. The DU145 cells secrete into conditional medium a specific IGF
      binding protein (IGFBP) precipitated by an antibody to IGFBP-1, and whose
      secretion is also suppressed by interruption of the EGF autocrine loop. This
      IGFBP may modulate the bioactivity of IGFs arising from endocrine or paracrine
      sources in vivo. After removal of IGFBPs from the conditioned medium, no
      secretion of either IGF-I or IGF-II by this prostate cancer cell line is detected
      by radioimmunoassay and radioreceptor assay, respectively.

PMID- 7511803
TI  - Effects of 4-MAPC, a 5 alpha-reductase inhibitor, and cyproterone acetate on
      regrowth of the rat ventral prostate.
AB  - Inhibitors of 5 alpha-reductase activity cause less involution of the rat ventral
      prostate (VP) than does castration. Studies were conducted in adult Sprague
      Dawley rats to evaluate the effects of a potent 5 alpha-reductase inhibitor, 4
      MAPC, and the antiandrogen, cyproterone acetate (CA), on DNA synthesis and
      apoptosis. In experiment 1, VP weight fell 33%, 53%, and 83%, and DNA per ventral
      prostate was reduced 24%, 46%, and 71%, by 4-MAPC, CA, and castration,
      respectively. In experiment 2, adult rats were castrated, and the VP involuted
      for 7 days prior to 3 daily injections of testosterone propionate (TP; 1 mg/kg/d)
      +/- 10 mg/kg/d of 4-MAPC or CA. 3H-thymidine incorporation into VP DNA was
      increased in castrated animals treated with TP, and 4-MAPC and CA reduced uptake.
      In experiment 3, animals were treated for 14 days with the same protocol as that
      used in experiment 2. VP weight was increased in all animals treated with TP when
      compared with castration, and was reduced by both 4-MAPC and CA. DNA in rats
      treated with TP was similar to that in intact animals. DNA was not reduced by 4
      MAPC, but was reduced by CA. The mRNA for TRPM-2, a marker of apoptosis, was
      increased only in untreated castrated rats. It appears that CA has a greater
      inhibitory effect than 4-MAPC on DNA synthesis. A major reason why castration
      reduces DNA more than either 4-MAPC or CA is that neither of these agents was
      able to increase programmed cell death to the degree seen with castration.

PMID- 7511804
TI  - Rooster comb and wattle tissues contain an anti-keratan sulfate monoclonal
      antibody epitope.
AB  - Glycosaminoglycan fractions isolated from either comb or wattle tissue were
      examined using ELISA for their antigenicities to AH12, a monoclonal antibody
      recognizing keratan sulfate. The results showed a positive antibody binding to a
      sulfated glycosaminoglycan fraction from either tissue. The treatment of the same
      fraction with keratan sulfate degrading enzyme, keratanase, or endo-beta
      galactosidase resulted in a decrease in its antigenicity. These findings
      indicated the presence of AH12 epitope (keratan sulfate disaccharide) in both
      tissues.

PMID- 7511805
TI  - Improved tyrosinase activity stains in polyacrylamide electrophoresis gels.
AB  - Mammalian tyrosinase exists in a variety of subcellular locations and maturation
      states that result from a complex post-translational processing with possible
      regulatory implications. So far, SDS-PAGE has proven to be the method of choice
      for the resolution of tyrosinase isoforms. However, the relatively poor
      sensitivity of the currently available specific activity stain based on
      incubation of the gels with L-dopa until the formation of melanin has severely
      limited the use of electrophoresis in regulation studies. Two alternative
      staining procedures are presented and discussed. The first one involves the
      fluorographic detection of radioactive melanin after incubation of the gels in
      the presence of L-[3-14C]-dopa. A similar method has already been used by others
      (Tsukamoto et al., 1992, Pigment Cell Res. [Suppl.] 2:84-89), but its performance
      has not yet been compared to the one of the dopa procedure. The sensitivity of
      this method can be varied by adjusting the isotopic dilution of the tracer and/or
      the time of exposure of the gel, but it is at least ten times higher than the one
      of the colorimetric stain. Moreover, the intensity of the bands is proportional
      to the initial tyrosinase activity over a wide range. Using this procedure, the
      activity present in the different subcellular fractions of melanocytes in culture
      can be easily detected. The second procedure involves the formation of a colored
      adduct between dopaquinone and MBTH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511806
TI  - Tyrosinase gene expression in human tissues.
AB  - The occasional occurrence of primary extra-cutaneous malignant melanomas (MM) has
      led to the hypothesis that melanocytes derived from the neural crest may be
      arrested in their migration and may undergo an in situ malignant transformation.
      However, aggregates of nevus cells have only rarely been identified by
      histological examination in a few organs other than skin and eye. Tyrosinase is a
      melanin biosynthetic enzyme that is considered one of the most specific markers
      of melanocytic differentiation. We have attempted to detect cells committed to
      the melanocytic lineage, in human tissues, by means of tyrosinase gene
      expression. Total RNA was extracted from normal and neoplastic tissues and
      analyzed using a highly sensitive reverse transcription PCR assay with primers
      specific for the tyrosinase gene. Peripheral blood mononuclear cells (PBMC) from
      healthy subjects were used as negative controls. Tyrosinase transcripts were
      identified in a wide range of normal organs such as skin, lymph nodes, antrum,
      colon, kidney, lung, testis, ovary, breast, and peripheral nerve. Tyrosinase RNA
      was also detected in neoplastic samples including benign cutaneous nevi, lymph
      nodes involved by MM, breast carcinoma, liposarcoma, malignant lymphoma, and
      schwannoma. PBMC from patients with metastatic MM were also positive, while no
      positivity was detected in blood specimens from patients with other cancers.
      Therefore, it appears likely that cells expressing the tyrosinase gene are
      present in a wide range of human tissues. Although these cells still have to be
      accurately identified, one could propose that they might correspond to either
      fully differentiated melanocytes, melanocytic precursors, or Schwann cells
      bearing potentialities of melanocytic differentiation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7511807
TI  - Modulation of normal human melanocyte dendricity by growth-promoting agents.
AB  - Dendrite formation and extension, which comprise a characteristic morphology of
      human normal melanocytes in the skin, represent one of the functional activities
      of melanocytes, the ability to transfer melanosomes into neighboring
      keratinocytes. However, the morphology of the melanocyte in vitro is usually
      quite different from that observed in vivo. it is probably due to the
      hyperproliferative condition of the melanocytes in culture. No studies have ever
      compared the effects of a single factor on both dendricity and proliferation at
      the same time. Therefore, we have compared the effects of six growth-promoting
      agents commonly used for melanocyte cultures on dendrite formation and
      proliferation. The addition of agents that increase the intracellular levels of
      cyclic adenosine monophosphate (cAMP)--dibutyryl cyclic adenosine monophosphate
      (db cAMP; 1 mM) or isobutylmethyl xanthine (IBMX; 0.1 mM)--had a strong effect on
      dendrite formation and a negative effect on proliferation. This was especially
      true with db cAMP. In the presence of 2% or 5% of heat-inactivated fetal bovine
      serum (FBS), dendrite formation was significantly increased as was proliferation.
      The number of dendrites was decreased in the culture with 12-o
      tetradecanoylphorbol-13-acetate (TPA), but cell growth was slightly increased.
      With human recombinant basic fibroblast growth factor (bFGF) (0.5, 1.0 ng/ml) in
      the presence of bovine pituitary extract (BPE) (60 micrograms/ml), cell growth
      was increased. With 2 ng/ml of bFGF, however, a strong inhibitory effect on
      proliferation was observed. However, dendrite formation was constant at all
      concentrations of bFGF tested (0.5, 1.0 or 2.0 ng/ml) with BPE (30 or 60
      micrograms/ml). In this study, we have demonstrated that dendrite formation was
      suppressed by the reagents that stimulate melanocyte proliferation, and vice
      versa, with the only exception being heat-inactivated FBS. Both dendrite
      formation and proliferation were induced by the heat-inactivated FBS. This
      approach is crucial to the development of an adequate culture system for
      proliferation and/or dendrite formation of normal human melanocytes. It is
      necessary to keep these aspects in mind as we further investigate the biology of
      melanocytes, especially the cell-to-cell interactions between melanocytes and
      keratinocytes, involved in melanogenesis and melanin pigmentation in vivo. This
      study also provides practical and important information for a future
      reconstitutive skin system composed of melanocytes, keratinocytes, and
      fibroblasts in a single culture medium.

PMID- 7511808
TI  - Dual appearances of pigment cells from in vitro cultured embryonic cells of
      Japanese flounder: an implication for a differentiation-associated clock.
AB  - The cells dissociated from developing embryos of Japanese flounder (Paralichthys
      olivaceus) are cultured in vitro to examine the developmental fate of their
      pigment cells in relation to establishment of bilaterally asymmetric integumental
      coloration in vivo. When neurula embryos are dissociated using trypsin-EDTA in
      Dulbecco's modified Ca(2+)-, Mg(2+)-free phosphate buffered saline and then
      cultured in vitro using L-15-based fetal calf serum-supplemented growth medium at
      20 degrees C, numerous pigment cells appear twice in the same culture with an
      interval of approximately 1 month even under similar culture conditions. The
      first group of pigment cells, which is relatively larger in cell size (about 70
      microns wide) and lower in cell density, emerges within 12 hr after plating,
      whereas the second, which is far smaller in cell size (about 30 microns) and
      overwhelmingly higher in cell density than the first, does so about 1 month after
      plating. The timing of their appearances in vitro is in good accordance,
      respectively, with that observed for the larvae under normal development in vivo;
      the first group appears at the period corresponding to hatching, whereas the
      second at the period corresponding to the completion of metamorphosis. Light
      microscopic examinations disclose that each group of pigment cells is composed of
      black melanophores and reflecting leucophores, and that the population density of
      melanophores and leucophores in the first group at the climax of appearance is
      approximated as 1:4. Typical xanthophores that are distributed in the skin of the
      larvae of this species are scarcely observed in culture in vitro.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7511809
TI  - Oat beta-glucan-amylodextrins: preliminary preparations and biological
      properties.
AB  - Amylodextrins with soluble beta-glucan contents from 1 to 10% were prepared from
      oats and the hypocholesterolemic properties of the latter were evaluated. The
      products are called OATRIM and can lower blood cholesterol by replacing animal
      fats rich in cholesterol in food products and, possibly, by the action of beta
      glucan in the body after consumption. In the chick model, decreased total blood
      cholesterol also resulted in increases of HDL cholesterol and decreases of LDL
      cholesterol. Processing conditions were found that gave the maximum amount of
      beta-glucan and desirable fat-replacement qualities with the least amount of
      color and flavor.

PMID- 7511810
TI  - Rigid-body docking with mutant constraints of influenza hemagglutinin with
      antibody HC19.
AB  - An automatic docking algorithm has been applied to the modeling of the complex
      between hemagglutinin from influenza virus and the Fab fragment of a monoclonal
      antibody raised against this antigen. We have introduced here the use of
      biochemical information provided by mutants of hemagglutinin. The docking
      procedure finds a small number of candidate solutions where three sites of escape
      mutations are buried and form hydrogen bonds in the interface. The localization
      of the epitope is improved by additional biochemical data about mutants that do
      not affect antibody binding. Five candidate solutions with low energy, reasonably
      well-packed interfaces, and six to ten hydrogen bonds are compatible with mutant
      information. One of the five stands out as generally better than the others from
      these points of views.

PMID- 7511811
TI  - Truncated desmin in PtK2 cells induces desmin-vimentin-cytokeratin
      coprecipitation, involution of intermediate filament networks, and nuclear
      fragmentation: a model for many degenerative diseases.
AB  - The earliest expression of truncated desmin in transfected PtK2 cells results in
      the formation of dispersed microprecipitates containing not only the truncated
      desmin, but also endogenous vimentin and cytokeratin proteins. Desmin
      microprecipitates without vimentin or vimentin microprecipitates without desmin
      are not observed. The microprecipitates involving cytokeratin invariably are also
      positive for desmin and vimentin. Over time, the precipitates enlarge into 1- to
      2-microns spheroids and then fuse into amorphous chimeric juxtanuclear masses
      that can occupy > 30% of the cell volume. Concurrently, first the vimentin and
      then the cytokeratin networks are resorbed. The chimeric precipitates are not
      recognized or marked for degradation by the lysosomal system. Ultimately the cell
      nucleus fragments and the cell dies. Similar protein complexes appear in many
      human and animal pathologies, suggesting that a similar protein-precipitation
      sequence initiated by the introduction of a mutationally or environmentally
      altered protein molecule is at work.

PMID- 7511812
TI  - Reaction of germinal centers in the T-cell-independent response to the bacterial
      polysaccharide alpha(1-->6)dextran.
AB  - Primary immunization of BALB/c mice with alpha(1-->6)dextran (DEX), a native
      bacterial polysaccharide, induces an unexpected pattern of splenic B-cell
      responses. After a peak of antibody-secreting B-cell response at day 4,
      deposition of dextran-anti-dextran immune complexes, as revealed by staining with
      both dextran and antibodies to dextran, occurs and persists in splenic follicles
      until at least the fourth week after immunization. Antigen-specific B cells
      appear and proliferate in such follicles, leading by day 11 to development of DEX
      specific germinal centers as characterized by the presence of distinct regions of
      DEX+ peanut agglutinin-positive (PNA+) cells. At this time, fluorescence
      activated cell sorter analysis also reveals the appearance of a distinct
      population of DEX+ PNA+ splenic B cells. In contrast, DEX+ PNA- cells,
      characterized by intense cytoplasmic staining, are present outside of splenic
      follicles, peak at day 4 to day 5, and persist until at least day 28. The
      frequency of these cells correlates with DEX-specific antibody-secreting cells,
      as detected by the ELISA-spot assay. Thus, in addition to the expected plasma
      cellular response, the typical T-cell-independent type II antigen, DEX,
      surprisingly also elicits the formation of antigen-specific germinal centers.
      These observations raise fundamental questions about the roles of germinal
      centers in T-cell-independent immune responses.

PMID- 7511813
TI  - Phosphacan, a chondroitin sulfate proteoglycan of brain that interacts with
      neurons and neural cell-adhesion molecules, is an extracellular variant of a
      receptor-type protein tyrosine phosphatase.
AB  - We have identified cDNA clones encoding a chondroitin sulfate proteoglycan of rat
      brain (previously designated 3F8 and now named phosphacan) that binds to neurons
      and neural cell-adhesion molecules. A sequence of 1616 amino acids deduced from a
      4.8-kb open reading frame contains the N-terminal amino acid sequence of the 3F8
      core glycoprotein as well as four internal CNBr, tryptic, and endoproteinase Lys
      C peptide sequences from the proteoglycan. The deduced amino acid sequence,
      beginning with a 24-amino acid signal peptide, reveals an N-terminal domain of
      255 amino acids homologous to carbonic anhydrases. The entire amino acid sequence
      deduced from our cDNA clones corresponds to the extracellular portion of a human
      receptor-type protein tyrosine phosphatase (RPTP zeta/beta) with which it has 76%
      identity, and the proteoglycan may represent an mRNA splicing variant of the
      larger transmembrane protein. RNA analysis demonstrated that a probe to the N
      terminal carbonic anhydrase domain of the proteoglycan hybridizes with rat brain
      mRNA of 9.5, 8.4, and 6.4 kb, whereas probes to the phosphatase domains hybridize
      with only the 9.5-kb message and with the 6.4-kb message (which corresponds to a
      previously identified variant of the transmembrane protein in which half of the
      extracellular domain is deleted). The 30 N-terminal amino acids of the 3H1
      chondroitin/keratan sulfate proteoglycan of brain are identical to those of the
      3F8 proteoglycan, and six internal tryptic peptide sequences also matched those
      found in sequenced peptides of the 3F8 proteoglycan and/or amino acid sequences
      deduced from the cDNA clones. We therefore conclude that the 3H1
      chondroitin/keratan sulfate proteoglycan and the 3F8 chondroitin sulfate
      proteoglycan represent glycosylation and possible extracellular splicing variants
      of a receptor-type protein tyrosine phosphatase. These proteoglycans may modulate
      cell interactions and other developmental processes in nervous tissue through
      heterophilic binding to cell-surface and extracellular matrix molecules, and by
      competition with ligands of the transmembrane phosphatase.

PMID- 7511814
TI  - Further perspective on the catalytic core and secondary structure of ribonuclease
      P RNA.
AB  - Phylogenetic comparative analyses of RNase P RNA-encoding gene sequences from
      Chlorobium limicola, Chlorobium tepidum, Bacteroides thetaiotaomicron, and
      Flavobacterium yabuuchiae refine the secondary structure model of the general
      (eu)bacterial RNase P RNA and show that a highly conserved feature of that RNA is
      not essential. Two helices, comprised of 2 base pairs each, are added to the
      secondary structure model and form part of a cruciform in the RNA. Novel sequence
      variations in the B. thetaiotaomicron and F. yabuuchiae RNA indicate the
      likelihood that all secondary structure resulting from canonical base-pairing has
      been detected: there are no remaining unpaired, contiguous, canonical
      complementarities in the structure model common to all bacterial RNase P RNAs. A
      nomenclature for the elements of the completed secondary structure model is
      proposed. The Chlorobium RNase P RNAs lack a stem-loop structure that is
      otherwise universally present and highly conserved in structure in other
      (eu)bacterial RNase P RNAs. The Chlorobium RNAs are nevertheless catalytic, with
      kinetic properties similar to those of RNase P RNAs of Escherichia coli and other
      Bacteria. Removal of this stem-loop structure from the E. coli RNA affects
      neither its affinity for nor its catalytic rate for cleavage of a precursor
      transfer RNA substrate. These results show that this structural element does not
      play a direct role in substrate binding or catalysis.

PMID- 7511816
TI  - Rice tungro bacilliform virus encodes reverse transcriptase, DNA polymerase, and
      ribonuclease H activities.
AB  - Rice tungro bacilliform virus (RTBV) is a newly described badnavirus and proposed
      member of the plant pararetrovirus group. RTBV open reading frame 3 is predicted
      to encode a capsid protein, protease (PR), and reverse transcriptase (RT) and has
      the capacity to encode other proteins of as yet unknown function. To study the
      possible enzymatic activities encoded by open reading frame 3, a DNA fragment
      containing the putative PR and RT domains was used to construct the recombinant
      baculovirus PR/RT-BBac. Trichoplusia ni insect cells infected with PR/RT-BBac
      were used in pulse-labeling experiments and demonstrated synthesis of an 87-kDa
      polyprotein that corresponds in molecular mass to that predicted from the PR/RT
      DNA coding sequence. The 87-kDa polyprotein was processed with concomitant
      accumulation of 62-kDa (p62) and 55-kDa (p55) proteins. Amino-terminal sequencing
      of p62 and p55 determined that they mapped to the PR/RT domain and shared common
      amino termini. p62 and p55 were purified and exhibited both RT and DNA polymerase
      activities using synthetic primer/template substrates. Only p55 had detectable
      ribonuclease H activity, an activity intrinsic to all reverse transcriptases
      studied to date. Characterization of the RTBV RT provides a biochemical basis for
      classifying RTBV as a pararetrovirus and will lead to further studies of these
      proteins and their role in virus replication.

PMID- 7511815
TI  - Ctk: a protein-tyrosine kinase related to Csk that defines an enzyme family.
AB  - We used the polymerase chain reaction with degenerate oligonucleotide primers to
      search for Csk-related kinases. A cDNA coding for a Csk-like protein-tyrosine
      kinase was cloned from mouse brain and was designated ctk, for csk-type protein
      tyrosine kinase. The 1.9-kb ctk mRNA was found to be expressed predominantly in
      brain and capable of encoding a 52-kDa protein-tyrosine kinase. The amino acid
      sequence of Ctk was found to possess 53% identity with mouse Csk, shared all the
      predicted structural features of Csk, and was capable of phosphorylating the
      carboxyl-terminal conserved tyrosine of Src family members. Our results thereby
      indicate that ctk represents a gene that defines a family of structurally and
      functionally related Csk-like protein-tyrosine kinases.

PMID- 7511817
TI  - Mutation detection by mismatch binding protein, MutS, in amplified DNA:
      application to the cystic fibrosis gene.
AB  - An experimental strategy for detecting heterozygosity in genomic DNA has been
      developed based on preferential binding of Escherichia coli MutS protein to DNA
      molecules containing mismatched bases. The binding was detected by a gel mobility
      shift assay. This approach was tested by using as a model the most commonly
      occurring mutations within the cystic fibrosis (CFTR) gene. Genomic DNA samples
      were amplified with 5'-end-labeled primers that bracket the site of the delta
      F508 3-bp deletion in exon 10 of the CFTR gene. The renatured PCR products from
      homozygotes produced homoduplexes; the PCR products from heterozygotes produced
      heteroduplexes and homoduplexes (1:1). MutS protein bound more strongly to
      heteroduplexes that correspond to heterozygous carriers of delta F508 and contain
      a CTT or a GAA loop in one of the strands than to homoduplexes corresponding to
      homozygotes. The ability of MutS protein to detect heteroduplexes in PCR
      amplified DNA extended to fragments approximately 500 bp long. The method was
      also able to detect carriers of the point mutations in exon 11 of the CFTR gene
      by a preferential binding of MutS to single-base mismatches in PCR-amplified DNA.

PMID- 7511818
TI  - Blocking of retroviral infection at a step prior to reverse transcription in
      cells transformed to constitutively express interferon beta.
AB  - We are developing methods for somatic-cell gene therapy directed against
      infection with human immunodeficiency virus, by enhancing antiviral resistance of
      target cells through the constitutive production of autocrine interferon (IFN).
      Using the human IFN-beta coding sequence under the constitutive low-expression
      control of a 0.6-kb murine H-2Kb promoter-fragment, we have constructed a
      retroviral vector, HMB-KbHuIFN beta, and have transformed cells of the T98G human
      neuroblastoma line, the U-937 human promonocytic line, and the CEM human
      lymphocytic line. These human IFN-beta-transformed cell populations have acquired
      a low, constitutive production of human IFN, while replicating at a rate similar
      to that of untransformed cells and of cells transformed with the control vector
      carrying a human IFN-beta sequence encoding an inactive, mutated protein. In the
      three different cell populations tested, transformation with the HMB-KbHuIFN beta
      vector resulted in a 1.3-2.3 log10 reduction in the number of cells infected with
      a defective amphotropic MFG-LaZ retrovirus. A kinetic study of the fate of the
      MFG-LacZ retrovirus in the culture medium and intracellularly immediately after
      exposure of the cells to virus revealed a significant reduction of the appearance
      of intracellular virus in human IFN-beta-transformed cells. A similar effect was
      obtained by treating untransformed T98G, U-937, and CEM cells with exogenous
      human IFN-beta. The blocking effect of autocrine or exogenous human IFN-beta on
      viral entry was not limited to virus specific for the amphotropic receptor but
      was also obtained in murine IFN-beta-treated NIH 3T3 mouse fibroblasts infected
      with an ecotropic MFG-LacZ retrovirus. Infection of human IFN-beta-transformed
      CEM cells with human immunodeficiency virus type 1 gave comparable results.
      Immediately following exposure of the cells to human immunodeficiency virus, a
      kinetic study of the fate of the virus failed to reveal the appearance of
      intracellular virus and showed that the majority of the input virus remained in
      the extracellular medium. We conclude that low autocrine IFN-beta synthesis, or
      exposure of cells to exogenous IFN-beta, prevents virus from getting inside the
      cells, regardless of the virus receptor involved.

PMID- 7511819
TI  - Antigen-binding glycosylation inhibiting factor from a human T-cell hybridoma
      specific for bee venom phospholipase A2.
AB  - We obtained human T-cell hybridomas that are specific for bee venom phospholipase
      A2 (PLA2) and constitutively secrete glycosylation inhibiting factor (GIF). Upon
      crosslinking of CD3, the hybridoma produced GIF having affinity for PLA2. When
      affinity-purified PLA2-binding GIF was used as an immunogen, monoclonal
      antibodies specific for the antigen-binding GIF were obtained. Monoclonal
      antibody 110BH3 bound the antigen-binding GIF but failed to bind the 13-kDa
      nonspecific GIF, as determined by both bioassay and ELISA. In contrast, 388F1, a
      monoclonal antibody against nonspecific GIF, gave ELISA signals with both the
      nonspecific GIF and the antigen-binding GIF. Gel filtration of affinity-purified
      antigen-binding GIF revealed the presence of a 72- to 80-kDa protein which gave
      ELISA signals with both 110BH3 and 388F1 and contained GIF bioactivity. Upon
      reduction and alkylation, the antigen-binding GIF dissociated into a 62- to 64
      kDa protein which gave positive ELISA with antibody 110BH3 but no signal with
      antibody 388F1, and a 15-kDa protein, which gave ELISA signal with the 388F1 but
      not with 110BH3. Immunoblotting of a PLA2-binding GIF preparation revealed that
      under reducing conditions, the antigen-binding GIF dissociated a 13-kDa peptide
      which reacted with polyclonal antibodies against recombinant GIF. The results
      indicate that the 13-kDa nonspecific GIF is a subunit of antigen-binding GIF. The
      PLA2-binding GIF has affinity for an epitope, representing amino acid residues 19
      28 in PLA2 which appears to be an external structure in the antigen.

PMID- 7511822
TI  - Protection from lethal irradiation by the combination of stem cell factor and
      tempol.
AB  - Cytokines that stimulate growth and differentiation of hematopoietic precursor
      cells have been used as protectors in vivo against ionizing radiation. Recently,
      we have shown that the nitroxide tempol is also an effective radiation protector
      in vivo. The purpose of the present study was to determine if the combination of
      tempol with stem cell factor (SCF, c-kit ligand) would provide enhanced radiation
      protection in C57 mice compared with the protection afforded by either agent
      alone. Mice were exposed to whole-body irradiation and assessed for survival at
      30 days after irradiation. No control mice survived doses of more than 9 Gy.
      Treatment of mice before and after radiation with SCF alone (100 micrograms/kg at
      -20 h, -4 h and +4 h) protected mice from radiation at doses of as high as 10 Gy
      (76% survival). Tempol (350 mg/kg) given 10 min prior to radiation was a
      radioprotector at 9 Gy (55% survival). The combination of SCF and tempol
      increased the survival of mice exposed to radiation doses up to 11 Gy (32%
      survival for the combination vs 4% for SCF alone and 0% for tempol alone; P <
      0.001 for the combination vs either agent alone). Lower doses of SCF alone (1
      microgram/kg) or tempol alone (275 mg/kg) did not protect mice from radiation.
      However, the combination of these reduced doses of SCF and tempol protected mice
      from lethal irradiation at 10 Gy. Stem cell factor and tempol given either singly
      or together were well tolerated by the animals. These data show that SCF and
      tempol are radiation protectors and that their radioprotective effects are more
      than additive when the agents are given together.

PMID- 7511821
TI  - Does PGE2 act as a mediator for endothelin release?
AB  - To investigate the effect of iloprost (ZK 36374) and thromboxane synthetase
      inhibitor UK 38485 on endothelin release by the intestinal vascular endothelium
      after ischemia/reperfusion (IR) injury, five experimental groups were formed. The
      groups consisted of sham, control, iloprost treated (ILO), UK 38485 treated
      (TSI), and iloprost + UK 38485 treated (ILO + TSI) groups. The last three groups
      received the corresponding agents and then the superior mesenteric artery was
      clamped for 30 min followed by 90 min reperfusion. Endothelin levels in the
      portal blood and malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene
      C4 (LTC4) levels in the intestinal tissue were determined. The MDA levels
      increased significantly in the control group and this increase was reversed in
      ILO, TSI, and ILO + TSI groups, the two drugs together showing a synergistic
      effect in preventing lipid peroxidation. The changes in the LTC4 levels were not
      significant among the groups. The increased endothelin levels in the control
      group were reversed in ILO and TSI groups but these two agents did not have a
      synergistic effect. Increased PGE2 levels were reversed with iloprost but neither
      UK 38485 nor the combination of the two agents was effective in decreasing PGE2
      levels. It is concluded that endothelin release after mesenteric IR injury is
      relatively unrelated to lipid peroxidation and the lipoxygenase pathway. The
      cylooxygenase pathway has a direct effect on endothelin release and PGE2 may act
      as a mediator.

PMID- 7511820
TI  - T-cell receptor usage by melanoma-specific clonal and highly oligoclonal tumor
      infiltrating lymphocyte lines.
AB  - Tumor-infiltrating lymphocytes (TIL) obtained from human melanomas can
      specifically lyse autologous tumor in vitro and mediate tumor regression in vivo.
      To develop more effective therapeutic reagents and to further understand the T
      cell response to tumors, the diversity of T-cell receptors (TCRs) involved in
      melanoma antigen recognition has been studied. The TCR variable (V) genes,
      joining (J) segments, and N diversity regions used by five clonal lines and one
      highly oligoclonal, melanoma-specific, CD8+ TIL line were examined utilizing PCR
      amplification with V gene subfamily-specific primers and anchor PCR. The TIL
      lysed multiple allogeneic melanomas expressing matched surface major
      histocompatibility complex class I molecules. TCR analysis confirmed the clonal
      nature of the TIL lines; however, the TCR repertoire was diverse. Even among the
      three HLA-A2 restricted TIL (TIL 1200, TIL F2-2, and TIL-5), no common V gene
      usage was found. Comparison of the third complementarity-determining regions of
      the TCRs from the HLA-A2 restricted TIL revealed no homology. Results presented
      here identify T-cell clonotypes that recognize epitopes on highly prevalent,
      shared melanoma tumor-associated antigens presented in the context of HLA-B55,
      HLA-A1, and HLA-A2. These T cells and the antigens they recognize represent
      important components for the design of new immunotherapies for patients with
      advanced melanoma.

PMID- 7511823
TI  - Coordinate regulation of proteins associated with radiation resistance in
      cultured insect cells.
AB  - Cultured TN-368 lepidopteran insect cells exhibit a pronounced resistance to the
      lethal effects of a variety of physical agents, including X rays and 254 nm UV
      light, as well as a large number of chemicals. The resistance to ionizing
      radiation has previously been associated with an inducible process which is not
      expressed in unirradiated cells or cells receiving less than some minimal amount
      of radiation necessary for activating the process. The studies in this paper were
      initiated in an attempt to identify and characterize the inducible proteins
      associated with the marked radiation resistance of the TN-368 cells. Cells were
      exposed to doses of 0, 25, 64 or 350 Gy of 137Cs gamma rays and incubated either
      for 3 h in medium containing [35S]methionine or for 2 h without labeling. Labeled
      cells were separated into nuclear and cytoplasmic fractions and proteins were
      analyzed on two-dimensional polyacrylamide gels. Unlabeled cells were used to
      isolate total RNA which was translated in vitro in a rabbit reticulocyte lysate
      system with 35S label. These translation products were also analyzed by two
      dimensional electrophoresis. Gamma irradiation of the TN-368 cells resulted in
      the de novo synthesis of several proteins as well as the complete inhibition of
      others. The number of such proteins identified was 19. These proteins ranged in
      size from 18-73 kDa, with a pI distribution of 4.7 to 6.1. In addition to the
      unique proteins, a large number of other proteins were also either up- or down
      regulated. These observations were made in both nuclear and cytoplasmic fractions
      as well as in the translation products of RNA produced after irradiation. These
      studies indicate that RNA and protein synthesis in lepidopteran cells are
      coordinately regulated in response to ionizing radiation and may participate in
      the pronounced radioresistance of the TN-368 cells.

PMID- 7511824
TI  - Novel mechanisms of fibroblast growth factor 1 function.

PMID- 7511825
TI  - Insulin-like growth factor I: molecular biology and relevance to tissue-specific
      expression and action.

PMID- 7511826
TI  - Biochemistry of the Src protein-tyrosine kinase: regulation by SH2 and SH3
      domains.
AB  - pp60c-Srs (c-Src) is the prototype for a family of cytoplasmic protein-tyrosine
      kinases involved in the control of signal transduction. In addition to the
      enzymatic kinase domain, c-Src has several noncatalytic domains which regulate
      Src tyrosine kinase activity in both a positive and a negative fashion.
      Phosphorylation of c-Src at Tyr527 in the noncatalytic C-terminal tail is a key
      mechanism for repression of c-Src tyrosine kinase activity. This inhibitory
      phosphorylation is apparently catalyzed by another cytoplasmic tyrosine kinase
      (Csk). Recent evidence suggests that the c-Src SH2 domain participates in this
      phosphorylation-dependent repression of kinase activity through an intramolecular
      association with the phosphotyrosine-containing C-terminus. The SH3 domain of c
      Src also negatively regulates c-Src tyrosin kinase activity, although the
      mechanism is as yet unknown. However, in the background of constitutively active
      transforming Src variants, such as a c-Src mutant with an amino acid substitution
      eliminating Tyr527 (527F c-Src) or the retroviral oncogene v-src product pp60v
      src (v-Src), both the SH2 and SH3 domains contribute positively to the enzymatic
      and biological activities of the Src tyrosine kinase through interactions with
      Src substrates and/or cellular regulators.

PMID- 7511828
TI  - 5 alpha-reductase inhibitors for the treatment of benign prostatic hyperplasia.

PMID- 7511827
TI  - The nitric oxide-cyclic GMP signal transduction system for intracellular and
      intercellular communication.
AB  - From our work and that of others, it is now quite apparent that the NO-cGMP
      system can function as an intracellular or intercellular signal transduction
      system (Murad et al., 1988, 1990; Murad, 1989a,b; Ishii et al., 1989, 1991). If a
      specific cell possesses both NO synthase and an isoform of guanylyl cyclase that
      is activatable with NO, then cGMP levels in that cell can be regulated by agents
      that alter NO synthase activity and NO formation (Fig. 1). NO, or a complex of NO
      which is liberated from the producing or donor cell, can also activate guanylyl
      cyclase in a neighboring or perhaps a distant cell to increase cGMP synthesis. In
      the latter scenario, NO or its carrier complex behaves as a paracrine substance,
      autacoid, or hormone. Interestingly, the liberated extracellular NO can also feed
      back and increase cGMP synthesis in the cell of origin. This is best demonstrated
      by the inhibitory effects of hemoglobin on agonist-induced cGMP accumulation in
      homogeneous cell culture systems where the hormone or agonist effects on cGMP are
      mediated by NO. Presumably, hemoglobin would not be permeable and could only trap
      or scavenge extracellular NO to account for its ability to decrease hormonally
      induced cGMP increases in homogeneous cell populations. There is no direct
      evidence that NO can act as an endocrine substance to increase cGMP synthesis in
      a distant target cell population. However, complexes or carrier states of NO that
      would liberate NO at a distant site could most certainly be viewed as
      endocrinological agents (hormones or autocoids). We suspect that appropriately
      designed experiments in the future will also support this role for NO as an
      endocrinological agent that can also function at a distance similar to classical
      hormones. Indeed, we believe that NO should be added to the list of agents that
      can function as a neurotransmitter, paracrine substance, and autacoid or hormone.
      It can also be viewed as an intracellular, as well as intercellular, messenger.
      To date, no substance has played such a diverse role in intracellular and
      intercellular signal transduction. Thus, NO appears to be a unique and simple
      molecule with diverse functions in signal transduction.

PMID- 7511829
TI  - Benign and malignant prostatic neoplasms: human studies.
AB  - Because the present ability to treat and cure patients with prostate cancer is
      limited to those patients with pathologically organ-confined disease, it has
      become increasingly important to diagnose this disease at an early stage, when
      cure is most likely. Recent advances in imaging may allow the urologist and the
      pathologist to make the diagnosis of prostate cancer much earlier in the natural
      course of the disease. It therefore becomes imperative to have methods available
      to predict which patients have a high probability of progressing so that
      treatment can be assigned logically and appropriately. Our current methods of
      prognosis determination (stage and grade) do not allow accurate assessment of
      tumor behavior in the majority of individual patients with prostate cancer.
      Therefore, more accurate quantification of nuclear and cellular changes that take
      place as a tumor progresses to take on the aggressive (metastatic) phenotype are
      urgently needed. Experimental techniques have proven useful in answering these
      questions and now seem ready for large-scale testing in clinical studies.

PMID- 7511830
TI  - [Synovial angiogenesis].
AB  - Synovial angiogenesis i.e. the formation of new capillaries from pre-existent
      capillaries, is a prominent feature of articular inflammation. Since its
      regulation is tightly controlled, angiogenesis should disappear after recovery
      from acute episode. However, it may persist in chronic synovial inflammation such
      as rheumatoid arthritis (RA). Thus RA should be considered as an "angiogenic
      disease". This is the result of biochemical events which have contributed to the
      breakdown of the extracellular matrix and to the release of angiogenic factors in
      the local micro-environment. The growth of the pannus is dependent on the local
      angiogenesis which contributes to the destruction of joint cartilage. The
      development of inhibitors of synovial angiogenesis could offer a new therapeutic
      hope in RA.

PMID- 7511831
TI  - [NO-synthase and the kidney].

PMID- 7511832
TI  - Thiol-proteindisulfide-oxidoreductase (proteindisulfide isomerase): a new plasma
      membrane constituent of mature human B lymphocytes.
AB  - The thiol-proteindisulfide-oxidoreductase (TPO, EC 1.8.4.2., proteindisulfide
      isomerase, EC 5.3.4.1.) is known as an cytoplasmatic enzyme, and is thought to be
      involved in the post-translational folding of disulfide containing proteins.
      Using monoclonal and polyclonal antibodies the authors were able to prove that
      this enzyme or an unknown homologous protein is localized also to the plasma
      membrane of B lymphocytes. In peripheral blood from healthy donors 11% of the
      mononuclear cells (PBMNC) expressed this surface antigen whereas in PBMNC of
      patients with B-cell chronic lymphocytic leukaemia 76% of the MNC were positive.
      This value correlates well with the known B-cell markers CD19 and CD20. However,
      this antigen is different from all known clustered B-cell markers.
      Immunoprecipitation analysis of PHA-stimulated PBMNC and of cells from patients
      suffering from chronic lymphocytic leukaemia revealed a membrane protein with the
      same molecular weight (61 kDa) as the TPO. These data suggest that this enzyme is
      present not only in the cytoplasm but also on the surface of B cells and that it
      is possibly involved in the regulation of the SH-SS status of the cell membrane
      proteins of B lymphocytes.

PMID- 7511833
TI  - Down-regulation of L-selectin surface expression by various leukocyte isolation
      procedures.
AB  - L-selectin, a cell surface glycoprotein expressed on lymphocytes, granulocytes,
      and monocytes, has been implicated in lymphocyte homing and extravasation of
      phagocytic leukocytes into areas of inflammation. Considerable differences of L
      selectin expression among various individuals has been reported, with clinical
      correlations to perinatal events, maturation, and circadian rhythm. In this
      study, L-selectin expression of various white blood cells was found to be
      differentially sensitive to ficoll-hypaque or percoll density gradient
      centrifugation. After density gradient centrifugation, a significant loss of
      median monocyte L-selectin expression was observed when compared to time and
      temperature-matched controls or results obtained by whole blood incubation with
      anti-L-selectin monoclonal antibodies followed by simultaneous leukocyte fixation
      and red cell lysis. Mock treatment itself was associated with a variable L
      selectin loss of monocytes but not lymphocytes or granulocytes. Ficoll-hypaque or
      percoll density gradient centrifugation resulted in significant L-selectin down
      regulation of lymphocytes while granulocytes separated from lymphocytes and
      monocytes by ficoll-hypaque or percoll retained full L-selectin surface
      reactivity. L-selectin downregulation was seen also after colloid sedimentation
      with hydroxy-ethyl starch. It is concluded that unseparated blood should be used
      for measuring L-selectin expression.

PMID- 7511834
TI  - A cationic protein from a urate-calcium oxalate stone: isolation and purification
      of a shared protein.
AB  - A protein extracted from a urate-calcium oxalate stone by electrodialysis is also
      excreted in the urine which served as the source material for its purification by
      FPLC after separation on an ACA44 column. It has an amino acid composition
      appropriate for a cationic protein. One peptide obtained by cyanogen bromide
      cleavage has significant (approximately 60%) homology with CD59 protein
      (protectin). Both proteins have wide distribution, the unknown having been found
      in bile, cholesterol gallstones, and the wall of the aorta. However, the two
      proteins appear to be immunologically different.

PMID- 7511835
TI  - Morphological and histochemical changes in intercellular junctional complexes in
      epithelial cells of mouse small intestine upon X-irradiation: changes of
      ruthenium red permeability and calcium content.
AB  - Changes of calcium-content and permeability of tight junction following X
      irradiation were investigated in mouse intestinal epithelial cells by electron
      microscopy. In the control animals the lower parts of tight junctional area as
      well as the other junctional elements and the intercellular space are labeled by
      pyroantimonate precipitates, which contain calcium as revealed by electron
      spectroscopy and electron energy loss spectrometry. X-irradiation, parallel with
      morphological changes, lead to rapid decrease of pyroantimonate precipitable
      calcium content and increase of the permeability of tight junctions indicated by
      the penetration of ruthenium red into the intercellular space. These changes were
      readily reversible following 0,5 Gy doses of irradiation however, they persisted
      up to 24 hours following 5 Gy irradiation. We conclude that irradiation at the
      applied doses can transiently destabilize the tight junctions in the epithelial
      layer of the small intestine, presumably through a calcium dependent mechanism.

PMID- 7511836
TI  - National protein and nucleic acid databases.

PMID- 7511837
TI  - [The clinical efficacy of verapamil in ventricular extrasystolic arrhythmia and
      parasystole].
AB  - An arrhythmogenic mechanism has been investigated pharmacologically by acute drug
      tests (ADT) and alternate block of slow calcium channels and fast sodium channels
      of the cellular membranes. ADT with verapamil reduced extrasystoles by 60% in 44%
      of patients demonstrating the predominance of calcium-dependent arrhythmogenesis.
      An antiarrhythmic efficacy of fast sodium channels blockers was ascertained in
      33% of the patients. ADT with rhythmilen and verapamil produced a satisfactory
      antiarrhythmic effect in 18% of the examinees. These patients seem to have
      parallel activation of both fast sodium and slow calcium channels. They received
      courses of both drugs. It is stated that a pharmacological analysis of
      extrasystolic arrhythmia allows inference on pathogenesis of myocytic electrolyte
      disturbances which serves the basis for adequate corrective therapy.

PMID- 7511838
TI  - [Apolipoprotein(a)--a marker of the atherosclerotic process].

PMID- 7511839
TI  - [Nonsurgical methods of treating prostatic adenoma].

PMID- 7511840
TI  - [Insect venom allergy].
AB  - Systemic allergic reactions to hymenoptera stings are most often mediated by
      venom-specific IgE antibodies. The most frequent symptoms are urticaria,
      angioedema, asthma and anaphylactic shock. Rarely, cerebral or myocardial
      ischemia with permanent damage may result from severe anaphylactic shock. Each
      year several individuals die in Switzerland from allergic reactions following
      hymenoptera stings. The most valuable diagnostic tests are skin tests and
      estimation of venom-specific serum-IgE antibodies. The most important drugs for
      emergency treatment are adrenaline and antihistamines. During anaphylactic shock,
      volume substitution may be essential. All patients with a history of severe
      systemic reactions should receive venom immunotherapy which induces complete
      protection in a high percentage of the patients.

PMID- 7511841
TI  - [The value of immunotherapy in treatment of IgE-induced allergic diseases].
AB  - Until today, immunotherapy is the only causal treatment of IgE-mediated allergic
      disease. Its efficacy has been demonstrated in controlled studies for rhinitis
      and bronchial asthma due to various pollens, house-dust mite and animal dander as
      well as for systemic allergic reactions following hymenoptera stings. This
      treatment is especially successful in younger patients with seasonal allergy of
      rather short duration and with sensitization only to few allergens. In order to
      avoid allergic side effects of this treatment, measures of precautions must be
      strictly observed. A close cooperation between patient, family practitioner and
      allergist is important for the success of this treatment.

PMID- 7511842
TI  - What determines the specification of cortical areas?

PMID- 7511843
TI  - Normal aging: regionally specific changes in hippocampal synaptic transmission.
AB  - Results of electrophysiological investigations of aging in the rodent hippocampus
      contradict the popular conception of the aging process as one of general
      deterioration. Such studies have revealed a selective pattern of both
      degenerative change and functional sparing in different physiological parameters
      of the same cells. In synaptic transmission, changes have been observed that
      might even be considered compensatory. The selectivity of the aging process is
      further demonstrated by the fact that it exhibits clear regional specificity,
      even among the different subfields of the hippocampus. The future challenges will
      be to understand both how these specific patterns of age-related neurobiological
      change arise, and how they lead to the cognitive changes that arise during normal
      aging.

PMID- 7511844
TI  - Stiff microtubules and neuronal morphology.
AB  - Neuronal processes contain high concentrations of two related microtubule
      associated proteins, MAP2 and tau. When MAP2 is expressed in non-neuronal cells
      the microtubules appear to be stiffer than those in control cells that do not
      express MAP2. A stiffening effect of MAP2 is further suggested by recent
      experiments with microtubules reassembled in vitro and by the fact that, under
      appropriate circumstances, MAP2-expressing cells can be induced to form processes
      that are long and cylindrical. Both MAP2 and tau contain homologous microtubule
      binding domains, consisting of three or four repeats of an 18 amino acid
      sequence, which we believe are responsible for the stiffening effect. Our
      hypothesis is that each repeat binds to a neighbouring tubulin subunit in the
      wall of the microtubule, tethering them together and reducing their freedom of
      movement relative to one another. Based on these considerations, we suggest that
      MAP2 and tau may contribute to the support of neuronal processes by making the
      microtubules they contain longer, more stable and stiffer than those in non
      neuronal cells.

PMID- 7511845
TI  - Neostriatal dopamine receptors.

PMID- 7511846
TI  - Messenger plasticity in primary sensory neurons following axotomy and its
      functional implications.
AB  - Following peripheral axotomy, long-lasting changes in the expression of
      neuropeptides and their receptors in primary sensory neurons are observed. These
      changes involve the downregulation of the excitatory peptides substance P and
      calcitonin gene-related peptide and the upregulation of the inhibitory peptides
      neuropeptide tyrosine and galanin, resulting in a reduction of transmission in
      the dorsal horn. The changes observed are thought to represent adaptive responses
      to limit the consequences of peripheral nerve damage to the organism as a whole
      and to promote survival and recovery of the individual neuron.

PMID- 7511847
TI  - Neostriatal dopamine receptors.

PMID- 7511848
TI  - The molecular genetics and evolution of primate colour vision.
AB  - Until recently, the genetic basis of colour vision could only be inferred from
      measuring the colour vision of family groups. However, in the past few years the
      sites of the genes for visual pigments have been located and sequenced. The genes
      that specify the opsins for the rod and short-wavelength cone pigments are
      located on the third and seventh chromosomes, respectively. In Old World primates
      the genes for the middle- and long-wavelength pigments are located on the q arm
      of the X chromosome in a head-to-tail array. The close sequence similarity of the
      two genes on the X chromosome leads to a high frequency of unequal inter- and
      intragenic recombination leading to gene deletion or the creation of hybrid
      genes. In New World primates there is only a single locus on the X chromosome for
      a middle- to long-wavelength cone pigment. However, three alleles can occur at
      this locus and each codes for a slightly different cone pigment. As a result
      there are three types of male dichromat and three types of female dichromat and
      trichromat in each species. Colour vision in New World primates might be an
      intermediate stage between the uniform dichromacy of non-primate mammals and the
      uniform trichromacy of Old World primates. Alternatively, colour vision in New
      World primates might be an adaptation to allow a wide variety of colour-vision
      types within a single family group.

PMID- 7511849
TI  - Signal integration in the nervous system: adenylate cyclases as molecular
      coincidence detectors.
AB  - Integrating multiple incoming messages simultaneously and discriminating
      'meaningful' signals from spontaneous neural activity represent central problems
      to the nervous system. One mechanism by which signal integration and signal-to
      noise resolution are achieved is the formation of temporal coincidence circuits
      by interacting transduction pathways. Signal integration via temporal coincidence
      detection is exemplified most readily by the way in which neural adenylate
      cyclases are regulated. This review will discuss the role of adenylate cyclases
      as coincidence detectors in the nervous system with special focus on adenylate
      cyclase type III, an isoenzyme that is found in large quantities in olfactory
      receptor neurons. The notion that olfactory transduction might also utilize an
      adenylate-cyclase-mediated temporal coincidence circuit strengthens the idea that
      signal integration via temporal-coincidence pathways is a universal feature of
      all neural adenylate cyclases.

PMID- 7511850
TI  - Spinules: a case for synaptic plasticity.

PMID- 7511851
TI  - Spinules: a case for synaptic plasticity.

PMID- 7511852
TI  - Long-term regulation of short-term transmitter release properties: retrograde
      signaling and synaptic development.
AB  - The dynamics of presynaptic transmitter release are often matched to the
      physiological properties and functions of the postsynaptic cell. In organisms
      ranging from cats to crickets, evidence suggests that retrograde signaling is
      essential for matching these presynaptic release properties to individual
      postsynaptic partners. Retrograde interactions appear to control the development
      of presynaptic, short-term facilitation and homosynaptic depression through
      local, retrograde signaling at the synapse.

PMID- 7511853
TI  - [Primary localization of malignant lymphoma in the urinary bladder?].
AB  - We report on the case of a malignant non-Hodgkin lymphoma with primary location
      in the urinary bladder of an 83-year-old woman. Diagnosis was established by
      transurethral resection of the tumor and histological examination. No clinical
      signs (e.g. alterations of peripheral blood count) or tumor generalization were
      observed. To date only 86 cases of primary localization of lymphoma in the
      urinary bladder have been described, whereas secondary involvement occurs in 5.4
      13% of cases.

PMID- 7511854
TI  - Early fall of antibodies against the motif 583-599 of gp41 in the sera of
      individuals with HIV-1 infection.

PMID- 7511855
TI  - [In vitro modification of plasma viscosity and erythrocyte aggregation by four
      plasma substitutes].
AB  - We tested the haemorheological effects of the addition of 3.5% oxypolygelatine,
      10% dextran 40, 6% dextran 75 or 5% albumin, respectively, to fresh donor blood
      of 25 healthy young persons. We examined the aggregation and the viscosity of
      substituent plasma mixtures in such various, but constant volume relations as may
      be present during intravenous infusion. Albumin reduced viscosity and
      aggregation, but especially dextran 75 increased both parameters significantly.

PMID- 7511856
TI  - [Metabolism and function of nitric oxide in the liver].
AB  - Nitric oxide (NO) is rapidly gaining importance as an ubiquitous biological
      mediator. Very different physiologic and pathophysiologic reactions are regulated
      by the endogenous biosynthesis or the release of NO from drugs. Besides its
      functions as an endothelium derived relaxing factor and inhibitory
      neurotransmitter, NO plays a key role in inflammation and immunity. The liver
      appears to have a central position in this complex scenario as both parenchymal
      and non-parenchymal cells synthesize NO under immune stimulation. Many aspects of
      the metabolism and the mode of action of NO, which are still unclear, remain to
      be further investigated and confirmed in the human system. Recent cloning of an
      inducible human NO synthase reveals new perspectives. The following article
      reviews the present scientific knowledge of the metabolism and function of
      hepatic NO.

PMID- 7511857
TI  - Lipase/amylase ratio: not helpful in the early etiological differentiation of
      acute pancreatitis.
AB  - The value of the lipase/amylase ratio for early etiological differentiation of
      acute pancreatitis was tested in 103 consecutive patients with acute pancreatitis
      from an ongoing prospective study. On admission, amylase, but not lipase, was
      significantly lower in alcoholics than in nonalcoholics in general and especially
      in patients with biliary pancreatitis. Alcoholics as a group had significantly
      higher lipase/amylase ratios than non-alcoholics and patients with acute biliary
      pancreatitis. But although the mean values of the ratio were significant,
      sensitivity, specificity, positive and negative predictive values of
      lipase/amylase ratio were insufficient to separate alcoholics from nonalcoholics,
      patients with alcohol-induced pancreatitis from those with biliary etiology, and
      patients with biliary pancreatitis from those with pancreatitis of other
      etiologies in the individual case. Finally, there was no correlation between the
      ratio and the amount of pancreatic changes as judged from computed tomography. We
      concluded that the ratio does not allow for early routine clinical
      differentiation between etiologies of pancreatitis and evaluation of the severity
      of the disease.

PMID- 7511859
TI  - [Physical therapy in cancer patients].
AB  - Malignant diseases and the resulting disorders may lead to the prescription of
      physical therapy. In addition, cancer patients may suffer from orthopaedic
      diseases which are treated by physical therapy, e.g. low back pain. In this
      review, cancer epidemiology, the prevailing forms of physical therapies, their
      applications in cancer patients, and possible cautions are being discussed.

PMID- 7511858
TI  - [Effect of frequent ventricular extrasystole on brain circulation in patients
      with coronary heart disease].
AB  - Animal experiments using the microsphere method indicate a 8% reduction of mean
      cerebral blood flow during parasystolic rhythm induced by ventricular pacing in
      comparison to a control group with sinus rhythm. The parasystolic rhythm causes
      changes of systemic arterial blood pressure, which are comparable to the
      hemodynamic effects of frequent premature ventricular contractions. Because a
      reduction of cerebral blood flow induced by frequent premature ventricular beats
      can be assumed by the results of the laboratory investigations, cerebral blood
      flow was determined in a clinical study in 19 coronary artery disease patients
      and in 11 healthy, age-adjusted volunteers using the 133Xenon-inhalation method,
      in order to investigate the effect of ventricular ectopics on cerebral perfusion.
      Simultaneously Holter monitoring was performed during cerebral blood flow
      measurements. Cerebral blood flow was estimated by the initial slope index, which
      is calculated from the early decay of the clearance curve, and by the mean
      cerebral blood flow index, which is calculated by the stochastic method. Grey
      matter blood flow is estimated by the two-compartment analysis. Cerebral blood
      flow in coronary artery disease patients is reduced versus controls. The initial
      slope indices were 45.2 +/- 5.1 s-1 and 57.4 +/- 7.2(-1), respectively (p <
      0.01). In patients with frequent ventricular ectopic activity (739/h) an
      additional reduction of cerebral blood flow was observed. The initial slope index
      was 42.6 +/- 6.3 s-1 (p < 0.01). The reduction of cerebral blood flow in coronary
      artery disease patients is partially due to the coincidence of coronary and
      cerebral artery disease. Frequent ventricular premature contractions might cause
      an additional reduction.

PMID- 7511860
TI  - [Complications in lymphedema].
AB  - Lymphodemas need treatment not only for the complaints they cause but also for
      their possible complications. Either complaints and complications can be
      eliminated or at least decreased by consistent physical therapy of edemas
      according to Asdonk.

PMID- 7511861
TI  - Epitopes recognized by HIV-SF2 nef-specific CD4+ T-cell clones generated from HIV
      1-uninfected donors.
AB  - Human T-cell clones with specificity to the HIV-1 nef protein were generated by
      the in vitro stimulation of peripheral blood mononuclear cells (PBMCs) from HIV-1
      seronegative donors with purified nef from the HIV-SF2 isolate produced in
      genetically engineered yeast. Here the characterization is described of a total
      of seven discrete clones derived from five different donors. Each clone was CD3+
      CD4+ CD8- as determined by FACS analysis. The epitopes recognized by these clones
      were identified using synthetic overlapping peptides spanning the entire length
      of nef. Six discrete helper T-cell epitopes located in five distinct regions of
      nef were identified by this approach. Three of these epitopes are more than 80%
      conserved among all HIV-1 nef proteins for which sequence data are available. The
      remaining epitopes are in regions of nef that vary among isolates. Many of the
      epitopes recognized by our clones overlap T-cell epitopes identified by others
      examining T-cell responses to nef in HIV-1-infected patients and immunized
      animals. Using partially class II-matched EBV-transformed B-cell lines, we were
      able to identify five different HLA class II alleles which encode restricting
      elements for the in vitro nef-specific proliferative response of these clones
      (DR1, DRw15(2), DRw6, DQw7, DP5).

PMID- 7511863
TI  - [Microcirculation of gastric mucosa in pathogenesis of stomach ulcer].
AB  - During the last decade, evidence increased that microcirculatory disorders play a
      pivotal role in the development of mucosal injury, and, hence, formation of
      gastric ulcer. Mucosal microcirculation is altered at least by two distinct
      mechanisms: Stimulation of acid secretion leads to a rise of blood flow in the
      acid-secreting areas, and, concomitantly, due to a steal-phenomenon to a decrease
      of mucosal capillary perfusion of the antrum, which results in temporary
      ischemia. In addition, surface noxae-induced release of potent mediators, such as
      histamine, leukotrienes, thromboxane, platelet-activating factor and reactive
      oxygen metabolites cause vasoconstriction, capillary stasis and increase of
      microvascular permeability (loss of endothelial integrity), which aggravate
      mucosal injury. Therefore, therapeutic strategies should consider leukotriene
      synthesis inhibitors, histamine-, thromboxane- and platelet-activating factor
      receptor antagonists, oxygen radical scavengers, as well as counteracting
      mediators and hormones, such as prostaglandins and somatostatin, inasmuch as
      these compounds have been shown to additionally prevent mucosal microvascular
      injury, in particular capillary perfusion failure and loss of endothelial
      integrity, during gastric ulcer formation.

PMID- 7511862
TI  - Immunogenicity of foot-and-mouth disease virus grown in BHK-21 suspension cells.
      Correlation with cell ploidy alterations and abnormal expression of the alpha 5
      beta 1 integrin.
AB  - BHK-21 suspension cells were characterized with regard to genetic and phenotypic
      features which might adversely affect the immunogenic properties of foot-and
      mouth disease virus (FMDV) grown therein. A positive correlation was found
      between number of passages in suspension culture and both prevalence of polyploid
      cells and reduced cell growth on surfaces. Suspension cells also revealed
      differences in the expression of RGD-specific integrins and, in particular, of
      alpha 5 beta 1, which was shown to work as an FMDV receptor structure. These
      features, along with the notable instability of a few non-structural FMDV A5
      proteins in infected cells, outline a new scenario, in which the reduced
      immunogenicity of FMDV might be accounted for by defined negative influences of
      the cell environment on viral replication.

PMID- 7511864
TI  - Cytokeratin expression in alopecia areata hair follicles.
AB  - Alopecia areata is a human hair disease of unknown etiology. Immunological
      mechanisms, alterations in the extracellular matrix and follicular growth
      abnormalities have been suggested as a possible cause. Here we compare the
      expression of cytokeratins in normal hair follicles to that of alopecia areata
      using immunohistology with monoclonal antibodies. A number of cytokeratins were
      specifically expressed in defined anatomical parts of the follicle; however, no
      gross qualitative or quantitative differences were found between normal and
      diseased scalp. Interestingly, the expression of cytokeratin 16, which is
      modulated by conditions that affect the rate of keratinocyte proliferation, was
      found to be unchanged in the outer root sheet of alopecia areata follicles. This
      is in contrast with earlier observations of a decrease in the expression of the
      proliferation-associated, Ki-67 nuclear antigen.

PMID- 7511865
TI  - E-selectin and interleukin-2 receptor alpha-chain expression in alopecia
      universalis.
AB  - A study of the histopathological abnormalities in a case of alopecia universalis
      was accompanied by immunohistochemical analysis of the expression of
      intercellular adhesion molecule-1 (ICAM-1) and E-selectin (formerly known as
      endothelial leukocyte adhesion molecule-1) within the skin. ICAM-1 expression on
      follicular epithelium co-localized with intraepithelial mononuclear cells (MNC)
      positive for the interleukin-2 receptor alpha-chain (IL-2R) or HLA-DR. Aberrant
      expression of E-selectin was observed on dermal endothelium. Although restricted
      to one case, these new observations concerning the expression of E-selectin and
      IL-2R in alopecia universalis are consistent with the view that extravascular
      trafficking of MNC into follicular epithelium may play a key role in the
      pathogenesis of alopecia universalis and that use of agents that interfere with
      this process may be an effective therapeutic strategy.

PMID- 7511867
TI  - Factor XIIIa expression in juvenile xanthogranuloma.
AB  - Dermal dendrocytes constitute the largest population among cells of
      dermatofibromas. In other histiocytic tumours, the exact nature of histiocytic
      cells is not known. We have searched for the presence of dermal dendrocytes in
      juvenile xanthogranulomas. The immunohistochemical study was performed on 9
      juvenile xanthogranulomas. We used monoclonal or polyclonal antibodies: anti
      XIIIa, HAM56, anti-S100, anti-NSE, anti-HLA-DR, anti-CD68 and anti-lysozyme.
      Phagocytic mononuclear cells (histiocytes, giant cells, Touton cells) did not
      express Langerhans' cell markers (S100, NSE ou HLA-DR). They weakly expressed
      markers of macrophages (CD68, lysozyme). There was a very strong binding by HAM56
      and anti-XIIIa. This expression was more evident on xanthomatous and newly
      appeared tumours than on fibrous tumours. The largest population of juvenile
      xanthogranuloma cells appeared to be constituted by dermal dendrocytes. These
      cells are perhaps the key-cells of a continuum of benign tumours, from juvenile
      xanthogranuloma to dermatofibroma, with different stages corresponding to
      different proportions of dendrocytes, lymphocytes and fibroblasts.

PMID- 7511866
TI  - Filaggrin immunoreactive composite keratohyalin granules specific to acrosyringia
      and related tumours.
AB  - The luminal cell layer of acrosyringia contains heterogeneous globular
      keratohyalin granules, some of which contain basophilic and eosinophilic
      components. Using immunoelectron microscopy we found that the majority of the
      granules, which are basophilic, are strongly reactive to an anti-filaggrin
      antibody, while the minority, which are eosinophilic, are not. Similar
      heterogeneous keratohyalin granules were observed in syringomas and in an eccrine
      syringofibroadenoma. Since such granules are not normally observed in other human
      cutaneous epithelia, it is suggested that these composite keratohyalin granules
      with partial filaggrin immunoreactivity might serve as a useful marker for
      acrosyringial differentiation in both normal and pathological material.

PMID- 7511868
TI  - Evaluation of barrier creams: an in vitro technique on human skin.
AB  - A method was developed to measure in vitro on human skin the effectiveness of
      barrier creams against three dyes (eosin, methyl-violet and oil red O) with
      different n-octanol/water partition coefficients (0.19, 29.8 and 165,
      respectively). Some galenic properties (water washability, water content and
      viscosity) of the products were also evaluated to try to understand the
      mechanisms of such a protection. The barrier creams were assayed by measurements
      of the dyes in the epidermis of protected skin samples after an application time
      of 30 min. Whereas some products showed some degree of protection, as claimed on
      the packaging, we demonstrated in several cases disagreement with the
      manufacturer's information. Surprisingly, petrolatum was found to provide the
      best protection of all tested products in our in vitro model. There was no
      correlation between the galenic parameters of the assayed products and the level
      of protections, indicating that neither the water content nor the consistence of
      the formulations influenced the protection effectiveness. In conclusion,
      regarding the possible skin effects of some irritants, our results stress that
      barrier creams should be used with caution, knowing the protection limits of some
      of the formulations marketed.

PMID- 7511870
TI  - Mechanisms of vancomycin-induced histamine release from rat peritoneal mast
      cells.
AB  - The mechanisms of vancomycin (VCM)-induced histamine release were studied with
      rat peritoneal mast cells. VCM (> 1 x 10(-3) M) released histamine from the
      isolated mast cells in a dose-dependent and noncytotoxic manner. In the absence
      of extracellular Ca2+, the histamine release was reduced markedly. When the
      intracellular Ca2+ was depleted, it was further decreased. The Fura-2-loaded
      single mast cells showed a biphasic increase in the intracellular Ca2+
      concentration ([Ca2+]i) by VCM: the first transient and the second sustained
      components. In the absence of extracellular Ca2+, the transient component was
      unchanged, while the sustained component was eliminated completely. The IP3
      content in the mast cells increased within 10 s after the application of VCM.
      These results suggest that VCM release histamine from rat peritoneal mast cells
      via an IP3 production and increase in [Ca2+]i.

PMID- 7511869
TI  - Some characteristics of the ATP-induced histamine release from and
      permeabilization of rat mast cells.
AB  - Extracellular adenosine 5'-triphosphate (ATP) induced a characteristic, dose
      dependent release of histamine and prostaglandin D2 (PGD2) from rat peritoneal
      mast cells. The process was relatively slow, non-cytotoxic, maximal at
      physiological pH and dependent on external calcium. Strontium and barium ions
      were able to substitute for calcium, although higher concentrations were required
      for maximal release. Cells stimulated in the absence of calcium progressively
      lost the ability to respond to subsequent reintroduction of the cation. The
      secretion of histamine induced by ATP was largely unaffected by the anti
      asthmatic drugs disodium cromoglycate and nedocromil sodium but was inhibited by
      structurally related flavonoids and by cAMP-active drugs. Importantly, the non
      hydrolysable guanosine 5'-triphosphate (GTP) analogue, GTP-gamma-S, elicited a
      dose-dependent release of histamine when introduced into mast cells permeabilized
      with ATP in the absence of external calcium. ATP thus appears to be a useful cell
      permeabilizing tool with which to study the biochemical processes involved in
      mast cell activation.

PMID- 7511874
TI  - Prenatal cocaine exposure and childhood psychopathology: a developmental
      analysis.
AB  - A rising number of children exposed to cocaine in utero are substantially
      vulnerable to mortality and morbidity expressed in a variety of physical,
      cognitive, emotional, motor, and social problems. Research on developmental
      outcomes in such children is reviewed and the interaction of prenatal and
      postnatal environmental factors, with a focus on the parent-child-environment
      transactional system, is discussed. Related societal and treatment issues are
      highlighted.

PMID- 7511873
TI  - Light microscopic diagnosis of microsporidiosis in patients with AIDS.
AB  - OBJECTIVE: In the past, the diagnosis of chronic intestinal microsporidiosis, an
      important cause of diarrhea in patients with AIDS, relied upon transmission
      electron microscopy (TEM). In this study, the sensitivity and specificity of the
      light microscopic (LM) diagnosis of microsporidiosis was determined. METHODS:
      Thirty-four consecutive jejunal biopsies from AIDS patients were evaluated at St.
      Luke's-Roosevelt and George Washington University Hospital Centers by several
      light microscopic stains, including hematoxylin and eosin, Gram stain, Giemsa
      stain, chromotrope 2R modified-trichrome stain, and Giemsa stain of mucosal touch
      preparations (TP). The results were compared to TEM, as the gold standard, and to
      estimates of parasite burden from plastic section light microscopy and TP.
      RESULTS: Microsporidiosis was diagnosed by TEM in 15 cases. The diagnosis also
      was reached by light microscopy in most cases. The sensitivities and negative
      predictive values of the different techniques ranged from 57% to 88%, while the
      specificities and positive predictive values ranged from 94% to 100%. All stains
      gave concordant results in 23 of 34 cases. The parasite burden was lower by TEM
      (p < 0.05) and TP in cases with discordant (false-negative) results than in those
      with concordant results, suggesting that a false-negative diagnosis is related to
      a low parasite burden. CONCLUSION: It should be possible to render the diagnosis
      of intestinal microsporidiosis by LM in most cases. TEM may be needed for the
      minority of cases with low parasite burden.

PMID- 7511872
TI  - Usefulness of Holter monitoring in predicting efficacy of amiodarone therapy for
      sustained ventricular tachycardia associated with coronary artery disease.
AB  - The ability of Holter monitoring to predict clinical events during amiodarone
      therapy was evaluated in 83 patients with coronary artery disease and inducible
      monomorphic ventricular tachycardia. Sixty-four patients (77%) had significant
      ventricular ectopy activity (> or = 10 ventricular premature complexes
      [VPCs]/hour) at baseline, and 19 (23%) did not; patients were similar in age (63
      and 65 years, respectively; p = 0.24) and ejection fraction (31 and 32%,
      respectively; p = 0.75). Over a mean of 23 +/- 17 months, there was no difference
      in arrhythmia recurrence (33 and 26%; p = 0.89) or sudden death (16 and 20%; p =
      0.94) in patients with and without significant ectopy, respectively. In patients
      with significant ectopy, amiodarone decreased VPC frequency from baseline to 2
      weeks, but not from 2 to 6 weeks. Forty-two patients had > 85% reduction in
      ectopy at 2 weeks; 20 patients did not. However, this reduction of simple VPCs
      did not predict a decrease in arrhythmic recurrence (29 vs 40%; p = 0.59) nor
      sudden death (25 vs 11%; p = 0.56) in patients with and without VPC suppression,
      respectively. Forty-five patients had Holter monitoring at 6 weeks. Twenty-one
      patients (47%) had > 95% suppression of ectopy, and 24 did not. Neither the
      recurrence (38 vs 38%; p = 0.54) nor sudden death (33 vs 13%; p = 0.45) rate was
      predicted by the degree of VPC suppression. Amiodarone is a powerful suppressant
      of VPCs, but Holter suppression of this ectopic activity is not predictive of
      clinical outcome.

PMID- 7511871
TI  - Release of histamine from isolated rat hearts during reperfusion is not dependent
      on length of ischemic insult, or contents of histamine in cardiac tissue.
AB  - Release of histamine (H) by ischemia-reperfusion injury was investigated in
      isolated rat hearts (Langendorff model). The effect of 10, 15, 20, 25, 30, 40 and
      60 min ischemia (n = 10 each) on H in the coronary effluent and in cardiac tissue
      was studied after 4 min reperfusion. Release of creatine kinase and lactate
      dehydrogenase in the coronary effluent increased with time of ischemia. Tissue H
      increased from 95 +/- 10 ng/g rat heart (mean +/- SEM) before ischemia to max 148
      +/- 10 ng/g after 20 min ischemia (p < 0.002), and increased also after 15 (p <
      0.01), 25 (p < 0.01), and 30 min (p < 0.045). H in the coronary effluent
      increased after 15 (from 16 +/- 3 to 26 +/- 2 pmol/min, p < 0.044), 30 (26 +/- 6
      pmol/min, p < 0.027), and 60 min ischemia (47 +/- 6 pmol/min, p < 0.0044).
      Release of H during ischemia-reperfusion is neither dependent on the severity of
      the ischemic insult, nor on the level of tissue H.

PMID- 7511875
TI  - Prevalence of depression in the terminally ill: effects of diagnostic criteria
      and symptom threshold judgments.
AB  - OBJECTIVE: Two issues that may influence the diagnosis of depression in the
      medically ill are 1) the severity with which symptoms must be expressed before
      they are considered clinically significant and 2) how to deal with somatic
      symptoms that may be caused by medical illness. This study used different
      approaches to case identification to examine prevalence rates for major and minor
      depression in a group of terminally ill cancer patients. METHODS: Semistructured
      diagnostic interviews were conducted with 130 patients receiving palliative care.
      Diagnoses according to the Research Diagnostic Criteria (RDC) were compared with
      diagnoses according to Endicott's revised criteria (which involve replacing
      somatic symptoms with non-somatic alternatives) when either a low-severity or a
      high-severity threshold for classifying RDC criterion A symptoms was used.
      RESULTS: A low-threshold (less stringent) diagnostic approach greatly increased
      the overall prevalence of major and minor depressive episodes with both the RDC
      and the Endicott criteria. With high thresholds, the RDC and the Endicott
      criteria were equivalent, whereas with low thresholds the Endicott substitutions
      identified fewer cases of major (but not minor) depression. CONCLUSIONS: Small
      differences between investigators in the applications of symptom-severity
      thresholds can result in large differences in prevalence rates for depression.
      However, the inclusions of somatic symptoms in the diagnostic criteria inflates
      the rates of diagnosis only when these symptoms are used in conjunction with a
      low-threshold approach.

PMID- 7511876
TI  - Differences in CSF concentrations of thyrotropin-releasing hormone in depressed
      patients and normal subjects: negative findings.
AB  - Since there have been reports of elevated CSF concentrations of thyrotropin
      releasing hormone (TRH) in depression, the authors compared the TRH levels of 17
      depressed patients and 19 normal subjects. All subjects underwent lumbar
      punctures after fasting overnight, and CSF concentrations of TRH were determined
      by radioimmunoassay. CSF concentrations of norepinephrine and monoamine
      metabolites were also measured. There was no significant difference between the
      two groups on any measure, and in the depressed patients there was no significant
      relation between CSF concentrations of TRH and thyrotropin-stimulating hormone
      responses to TRH infusion.

PMID- 7511878
TI  - Detection of a shared colon epithelial epitope on Barrett epithelium by a novel
      monoclonal antibody.
AB  - OBJECTIVE: To determine if there is a reactive epitope common to colonic
      epithelium and Barrett epithelium, a premalignant metaplastic columnar-lined
      esophagus, usually arising as a complication of chronic reflux esophagitis.
      DESIGN: A monoclonal antibody, 7E12H12 (IgM isotype), developed against a colonic
      epithelial protein was used in a sensitive immunoperoxidase assay using formalin
      fixed, paraffin-embedded tissue. One hundred sixteen tissue specimens from the
      esophagus, stomach, duodenum, and jejunum were examined. Twenty-two biopsy
      specimens were taken from 22 patients with benign Barrett epithelium, and 12
      specimens were obtained from 12 patients with adenocarcinoma of the esophagus
      arising in Barrett epithelium. The remaining 85 tissue specimens were obtained
      from various parts of the upper gastrointestinal tract of patients with or
      without disease states. RESULTS: 21 of 22 (95%) Barrett epithelium specimens and
      all 12 adenocarcinomas arising from Barrett epithelium reacted with the 7E12H12
      monoclonal antibody. Other tissues from esophagus, gastroesophageal junction,
      stomach, duodenum, or jejunum did not react. Squamous cell carcinoma of the
      esophagus also did not react. CONCLUSIONS: Barrett epithelium shares phenotypic
      expression of colonic epithelium. The 7E12H12 monoclonal antibody may provide
      insight into the origin and cellular lineage of Barrett epithelium.

PMID- 7511877
TI  - Detection of rotavirus in cerebrospinal fluid and blood of patients with
      convulsions and gastroenteritis by means of the reverse transcription polymerase
      chain reaction.
AB  - Rotavirus RNA was detected in the blood and cerebrospinal fluid from eight
      Japanese children with convulsions and gastroenteritis in the acute stage by
      means of the reverse transcription polymerase chain reaction. This may suggest
      that rotavirus invades the central nervous system through blood vessels.

PMID- 7511879
TI  - The correlations of surrogate markers with anti-hepatitis C virus and other
      disease markers.
AB  - Testing of donors' sera for the level of alanine aminotransferase (ALT) and the
      presence of hepatitis B core antibody (anti-HBc) has been required since 1986 as
      "surrogate" tests for non-A, non-B post transfusion hepatitis (NANB-PTH). With
      the availability of a test for the antibody to hepatitis C virus (HCV), the need
      for these two tests and their impact on one hospital are reviewed. Precisely 12.3
      percent of the donors were excluded for reactivity to surrogate disease markers
      but no reactivity to "true" markers. The positive predictive values of these
      surrogate tests were low and comparable (varying from 7.4 percent to 30 percent).
      In view of the high rate of donor exclusion and the low rate of correlation with
      "true" disease markers, the need for these tests needs to be reassessed.

PMID- 7511880
TI  - Aprotinin aerosol treatment of influenza and paramyxovirus bronchopneumonia of
      mice.
AB  - The therapeutic efficacy of aerosolized aprotinin, a natural proteinase
      inhibitor, against influenza and paramyxovirus bronchopneumonia of mice is shown.
      Small-particle aerosol of aprotinin solution was generated by a Collison type
      nebulizer and infected mice were exposed to aerosol atmosphere by four 30-40 min
      incubations per day for 6 days. This regimen provided an inhalation aprotinin
      dosage of approx. 6 micrograms/mouse/day. With such treatment more than 50% of
      mice infected with lethal doses of either influenza virus or paramyxovirus were
      protected from death. A suppression of the development of fatal hemorrhagic
      bronchopneumonia and a normalization of the body weight gain were observed in
      infected mice treated with aerosolized aprotinin. These data suggest that low
      doses of aerosolized proteinase inhibitors could be successfully applied against
      respiratory influenza-like virus diseases.

PMID- 7511881
TI  - Interferon treatment enhances the expression of underphosphorylated (biologically
      active) retinoblastoma protein in human papilloma virus-infected cells through
      the inhibitory TGF beta 1/IFN beta cytokine pathway.
AB  - Interferons (IFN) regulate transcription of certain genes playing a role in cell
      proliferation. Targets of IFN action may include tumor suppressor genes such as
      the retinoblastoma (RB) gene and cytokines such as transforming growth factor
      beta 1 (TGF beta 1) and IFN beta which are inhibitors of epithelial cell
      proliferation. Using reverse transcription followed by PCR amplification, an
      increase of those growth inhibitory gene mRNA levels (TGF beta 1, IFN beta and
      RB) were found after interferon treatment in condylomas harboring non-oncogenic
      human papilloma virus (HPV 6/11) types, in an oncogenic HPV 16-containing cell
      line, and in a HPV negative, epidermoid carcinoma cell line. In addition,
      immunodetection by Western blot demonstrated a higher proportion of
      underphosphorylated (active form) retinoblastoma gene protein (pRB) after IFN
      treatment due to the decrease in the phosphorylating cdc2 kinase levels. Changes
      in the phosphorylation pattern of pRB together with the increased expression of
      those inhibitory genes represent a growth inhibited state in those cells as
      demonstrated by diminished c-myc expression. Since the extent of c-myc inhibition
      was significantly lower in the case of oncogenic HPV infection, a role of viral
      oncoproteins in abrogation of the antiproliferative effect of IFN therapy could
      be considered. These results demonstrate a new mechanism via which IFNs exert
      their antiproliferative effect on HPV-infected cells by affecting the expression
      and phosphorylation of the RB tumor suppressor gene, through the inhibitory TGF
      beta 1/IFN beta cytokine pathway.

PMID- 7511882
TI  - Effect of methylprednisolone on angiogenesis in syngeneic rat tracheal grafts.
AB  - Airway anastomotic complications remain a cause of morbidity after clinical lung
      transplantation. The use of corticosteroid therapy to control pulmonary rejection
      has raised concern over delayed airway healing. We therefore investigated the
      hypothesis that the effects of methylprednisolone (MP) impair the
      revascularization and epithelial regeneration of heterotopic syngeneic tracheal
      isografts. Lewis rat tracheal segments were wrapped in omentum and implanted in
      the abdomen of recipient rats. All recipients received cyclosporin A (CsA) (5
      mg.kg-1.day-1) and were randomly allocated into three groups of 12 rats each
      according to the daily MP dose: group II, no MP; group III, 1 mg.kg-1.day-1; and
      group IV, 2 mg.kg-1.day-1. In each group, 6 animals were sacrificed after 7 and
      14 days. Normal, untreated rats served as controls (group I). Epithelial
      regeneration was assessed histologically by a blinded subjective scoring system
      and by measurement of epithelial thickness. Tracheal revascularization was
      quantitated in terms of the number of blood vessels per square millimeter of
      tracheal wall and the vessel area was quantitated in terms of the percentage of
      the tracheal wall area. In animals treated with MP and CsA, the trachea exhibited
      significantly better regeneration after 14 days than it did in animals treated
      only with CsA. Epithelial regeneration was improved between 7 and 14 days in the
      groups treated with MP (group III, p = 0.01; group IV, p = 0.04). The epithelial
      thickness for all three study groups was significantly greater than that in the
      control group and returned toward normal after 14 days.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7511883
TI  - Tolerance of epicardial coronary endothelium and smooth muscle to hyperkalemia.
AB  - Results of previous studies have suggested that high K+ concentrations in
      cardioplegic solutions may be detrimental to coronary endothelium in perfused
      hearts, as determined from changes in the coronary flow rate, but the direct
      functional changes in endothelium secondary to hyperkalemia have not been fully
      studied. To determine the effect of the K+ concentration in a physiologic
      solution (Krebs') and in St. Thomas' cardioplegic solution, and the effect of
      exposure time on endothelium and smooth muscle, porcine coronary artery rings
      were set up in organ baths under a physiologic pressure. The effect of exposure
      to Krebs' solution containing 5.9 or 50 mmol/L K+ or to St. Thomas' solution
      containing 16 or 50 mmol/L K+, for either 2 hours (group I) or 4 hours (group
      II), was examined. The solutions were continuously aerated with 95% oxygen and 5%
      carbon dioxide to exclude the effects of ischemia and hypoxia. The rings were
      then washed and contracted with K+ (25 mmol/L). The ability to release
      endothelium-derived relaxing factor (EDRF) in response to an EDRF stimulus
      (substance P) was used as an index of endothelial function. Smooth muscle
      function was evaluated in terms of the K(+)-induced contraction force and the
      relaxation induced with glyceryl trinitrate, in addition to the maximal substance
      P-induced relaxation. The maximal relaxation induced by substance P did not
      decrease by incubation with 50 mmol/L K+ in any group (p > 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7511884
TI  - Changes in vascular permeability with ischemic time, temperature, and inspired
      oxygen fraction in isolated rabbit lungs.
AB  - The capillary filtration coefficient (Kf) is one of the most accurate measures of
      change in pulmonary vascular permeability and has been used in various models of
      acute lung injury. To evaluate the isolated effects of ischemia on Kf, we have
      developed an ex vivo rabbit lung model in which the influences of reperfusion are
      eliminated. The current study was designed to validate this model by determining
      the effect of cold flushing with low-potassium-dextran solution containing 1%
      glucose (LPDG), ischemic time, temperature, and inspired oxygen fraction on Kf.
      On completion of the ischemic period, the ventilated lungs, with the heart still
      attached, were suspended from a strain-gauge force transducer. After the lungs
      were flushed with 50 mL hetastarch solution (6% hetastarch solution with
      physiologic saline solution), the left atrial drainage cannula was occluded and
      the pulmonary artery pressure was incrementally increased by elevation of the
      reservoir. The Kf was calculated as the slope of the line relating the weight
      gain rate and pulmonary capillary pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511885
TI  - 1986: Pharmacological, hematological, and physiological effects of a new
      thromboxane synthetase inhibitor (CGS-13080) during cardiopulmonary bypass in
      dogs. Updated in 1994.

PMID- 7511886
TI  - Changing physician PSA ordering patterns through education.

PMID- 7511887
TI  - [Allergic characteristics of bronchial asthma in the elderly].
AB  - Allergic characteristics were investigated in asthma patients older than 60 years
      of age. Among these asthmatic patients: 1. About 37% showed negative immediate
      skin response to all antigen extracts tested. 2. The frequency of positive
      immediate skin response to house dust, house dust mite, Japanese cedar and
      Alternaria decreased with aging. 3. There was no difference in the frequency of
      positive immediate skin response to Candida antigen among patients in different
      age groups. Candida was the antigen that most frequently produced positive
      immediate skin response among the patients over 50 years old. 4. There was no
      difference between skin-positive elderly asthmatics and young asthmatics in the
      frequency of positive IgE antibody titer, bronchial response, conjunctival
      response and histamine release from peripheral leukocytes by specific antigens.
      These findings show that atopic asthmatics are less frequently found in elderly
      asthmatic patients than in young patients. Nevertheless, there is no difference
      in the characteristics of atopy, except in the response to Candida antigen.

PMID- 7511889
TI  - Endoscopic photography: a valuable and cost-effective adjunct to patient care.

PMID- 7511888
TI  - [Chemical iodination of hormonogenic tyrosine residues of human thyroglobulin is
      critical for the production of anti-thyroglobulin autoantibody and for the
      induction of experimental autoimmune thyroiditis in mice].
AB  - There is evidence from animal models that the iodine content of thyroglobulin
      (Tg) may influence its antigenicity in thyroid autoimmunity. To elucidate the
      effect of iodination of hormonogenic sites of human Tg (hTg) on its
      autoantigenicity, a synthetic peptide (TB: hTg 2546-2571), containing two
      hormonogenic tyrosine residues of hTg, and a chemically-iodinated peptide (TB-I)
      were prepared. We immunized C3H/He (H-2k) mice, a high responder strain to Tg,
      and BALB/c (H-2d), a low responder strain, with TB or TB-I plus
      lipopolysaccharide. Lymph node cells from the two strains immunized with TB or TB
      I proliferated in response to both TB and TB-I. Anti-Tg autoantibodies were
      detected in both strains when immunized with TB-I, while immunization with TB
      failed to produce anti-Tg antibodies. Furthermore, one of the C3H/He mice
      immunized with TB-I developed diffuse thyroiditis, but BALB/c mice did not. These
      findings indicate that the iodination of the hormonogenic tyrosine residues of
      hTg, in other words, the synthesis of mono- and di-iodotyrosine (MIT and DIT)
      residues, is necessary for the production of anti-Tg autoantibodies in high and
      low responder mice and for the induction of autoimmune thyroiditis in high
      responder mice.

PMID- 7511890
TI  - Corticotropin-releasing factor stimulates Ca2+ influx in cultured rat astrocytes.
AB  - Corticotropin-releasing factor (CRF) increased intracellular Ca2+ concentration
      in single astrocytes. The effect in increasing intracellular Ca2+ was not
      observed in Ca2(+)-free solution. Furthermore, CRF at concentrations more than 10
      nM stimulated 45Ca2+ uptake in cultured rat astrocytes. The action was blocked by
      alpha-helical CRF(9-41) in a competitive manner, but not by nifedipine and 3,4
      dichlorobenzamil. On the other hand, CRF did not stimulate cAMP formation, cGMP
      formation and phosphoinositide hydrolysis in astrocytes. These results indicate
      that CRF increases Ca2+ influx via an activation of CRF receptors in a cAMP
      independent mechanism in cultured astrocytes.

PMID- 7511892
TI  - Expression of fibroblast growth factor gene family and its receptor gene family
      in the human upper gastrointestinal tract.
AB  - All of 13 human esophageal cancer cell lines contained mRNAs for both basic
      fibroblast growth factor (bFGF) and its receptor, FGFR1/N-sam protein, while they
      did not have mRNAs for keratinocyte growth factor (KGF) despite the presence of
      mRNAs for the KGF receptor gene, K-sam. The results indicate that in human
      esophageal cancer, bFGF plays roles in an autocrine manner, while KGF acts as a
      paracrine mediator. In contrast, only one of seven human gastric cancer cell
      lines contained bFGF mRNAs, while three out of the seven had mRNAs for FGFR1/N
      sam protein. The KGF gene was not expressed in any of the gastric cancer cell
      lines, while K-sam mRNAs were detected in six out of the seven. The results
      demonstrate that in most human gastric cancers, bFGF does not act as an autocrine
      mediator, while KGF acts as a paracrine factor. The mRNAs for the other four
      members of the fibroblast growth factor (FGF) family, including acidic FGF, int-2
      protein, hst-1 protein, FGF5 protein and FGF6/hst-2 protein could not be detected
      in the esophageal and gastric cancer cell lines.

PMID- 7511891
TI  - Preparation of a subtractive cDNA library enriched in cDNAs which expressed at a
      high level in cultured senescent human fibroblasts.
AB  - Subtracted cDNA library was prepared by subtracting [cDNA from young growing SV40
      transformed human fibroblasts] from [cDNA from growing SV40-transformed
      fibroblasts in extended lifespan]. Isolated cDNA clones which expressed at high
      level in life-extended transformed cells also expressed at high level in normal
      senescent fibroblasts but did at low level in growing and growth-arrested young
      cells. Neither fibronectin nor procollagen cDNA was isolated. This cDNA library
      is useful for isolation of senescent-specific cDNA species which express at high
      level in normal senescent cells but at low level in growing and growth-arrested
      young cells, avoiding growth-arrest-specific cDNAs.

PMID- 7511894
TI  - The role of reactive oxygen species in the degradation of lindane and DDT.
AB  - We have studied the photodegradation reactions of lindane and DDT under sunlight
      (72 hr) or a solar simulator (2 hr) either directly or in presence of selected
      photodynamic sensitizers. Direct photolysis did not cause noticeable degradation
      of the pesticides (below 1% in both the cases). However, addition of benzophenone
      or rose bengal to the irradiation solution of lindane resulted in 88% and 47%
      degradation, respectively, under sunlight. Similar experiments carried out with
      DDT resulted in 89%, 50% and 32% degradation with benzophenone, rose bengal and
      methylene blue, respectively. All the photosensitizers used for the study have
      been shown to induce photooxidation reactions by generation of reactive oxygen
      species. These studies suggest that by employing certain naturally occurring
      photosensitizers with reactive oxygen generation potential under sunlight, an
      effective method for safe removal of pesticides and other environmentally
      persistent agents from the surface of earth can be developed.

PMID- 7511893
TI  - A hippocampal protein associated with paraneoplastic neurologic syndrome and
      small cell lung carcinoma.
AB  - A hippocampal 38 kd autoantigen recognized by an autoantibody from the serum of a
      patient with paraneoplastic limbic encephalitis (PLE) and small cell lung
      carcinoma (SCLC) was isolated by screening a human hippocampal cDNA library. The
      1,991-nucleotide ple21 clone was obtained and the deduced 350-residue protein
      encoded by the ple21 cDNA clone was found to be highly homologous to the neuron
      specific RNA recognition motifs (RRMs)-containing proteins. The homologies were
      confined to the RRMs and the RRM connecting region. The presence of RRM in the
      antigenic protein may be important in the pathogenesis of SCLC-associated
      paraneoplastic neurologic syndrome.

PMID- 7511895
TI  - [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P induces apoptosis in lung cancer
      cell lines in vitro.
AB  - The broad spectrum antagonist [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P has
      been shown previously to inhibit the growth of small cell lung cancer cells both
      in vitro and in vivo. To elucidate further the pathways involved in the growth
      inhibitory actions of [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P we have
      examined the effect of this agent on cell viability and the induction of
      apoptosis in small cell and non-small cell lung cancer cells. Treatment of lung
      tumor cells with [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P caused a
      concentration-dependent loss of cell viability which was accompanied by the onset
      of apoptosis, as defined by cytological criteria and DNA fragmentation. This
      effect occurred in both small cell and non-small cell lung cancer cells and was
      not dependent on de novo protein synthesis. Such findings indicate that the
      antiproliferative action of [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P
      involves a signal transduction pathway for apoptosis.

PMID- 7511896
TI  - The Bacillus subtilis SRP54 homologue, Ffh, has an intrinsic GTPase activity and
      forms a ribonucleoprotein complex with small cytoplasmic RNA in vivo.
AB  - B. subtilis Ffh is a homologue of SRP54, which is one component of the mammalian
      signal recognition particle. B. subtilis Ffh was expressed in E. coli as a
      derivative with a hexa histidine tag at the COOH terminus and purified to near
      homogeneity. The purified Ffh had intrinsic GTPase activity as predicted from its
      amino acid sequence. Using antiserum against Ffh, we also demonstrated that B.
      subtilis Ffh forms a complex with scRNA which is a B subtilis homologue of the
      RNA component of SRP in vivo, and that half of the resulting complex is found in
      the peripheral fraction of the cytoplasmic membrane where the initiation of
      protein translocation occurs. These findings provide evidence of a
      ribonucleoprotein complex in B. subtilis, reminiscent of SRP.

PMID- 7511897
TI  - Evidence for multiple inducible cytochrome P450 isozymes in SENCAR mouse skin by
      pyridine.
AB  - Pyridine, an amphipathic solvent, is widely used in industry and is also a
      constituent of tobacco and its smoke. Since, in addition to inhalation and
      ingestion, pyridine is also readily absorbed through skin, we assessed the effect
      of skin application of pyridine on monooxygenase activities and cytochrome P450
      (CYP) isozymes and CYP mRNA levels in the skin of SENCAR mice. Compared to
      controls, a single topical application of pyridine (30 or 50 mg/100 g body
      weight) resulted in induction of cutaneous 7-ethoxyresorufin O-deethylase, 7
      pentoxyresorufin O-depentylase, and erythromycin N-demethylase activities.
      Pyridine treatment also resulted in an increase in reactivity with monoclonal
      antibodies directed against CYP 1A1, 2B1 and 3A. In Northern blot analysis,
      treatment of pyridine also showed a significant increase in mRNA for Cyp1a-1 in
      the skin. These data indicate that murine skin contains multiple inducible CYP
      isozymes, and that pyridine results in the induction of at least three families
      of CYP in murine skin.

PMID- 7511898
TI  - Oxidative stress induces NF kappa B DNA binding and inducible NOS mRNA in human
      epithelial cells.
AB  - Free radicals generated by a partial reduction of O2 pose a serious threat to
      tissues and vital organs and cells. The major site of interaction between the
      lung and inhaled oxidants is the epithelium. We have examined the effect of
      pyrogallol, an O2- generator, on the ability of human epithelial cells to produce
      active DNA binding proteins and inducible nitric oxide synthase (iNOS) mRNA in
      cultured A549 epithelial cells. NF kappa B binding in the nuclei of these cells
      was determined by electrophoretic mobility shift assays. iNOS mRNA was measured
      using reverse transcription of PCR. There was a time- and concentration-dependent
      induction of NF kappa B binding, followed by a time and dose dependent increase
      in iNOS mRNA levels. These results suggest that in airways the initial response
      to oxidative stress may be to induce NF kappa B-responsive genes, such as iNOS,
      which may play an important role in defending the airway against oxidative
      stress.

PMID- 7511899
TI  - Regulation of folate-binding protein gene expression by DNA methylation in
      methotrexate-resistant KB cells.
AB  - Folate-binding protein (FBP) is responsible for the cellular transport of folate
      and methotrexate (MTX) in human KB (nasopharyngeal epidermoid carcinoma) cells.
      The levels of membrane-associated FBP and FBP mRNA are decreased 70-80% in an MTX
      resistant KB subline (KB1BT) (Hsueh C-T and Dolnick BJ, Oncol Res 4: 497-505,
      1992). Southern blot analysis did not reveal any differences in FBP gene
      organization or copy number between KB1BT and KB cells. However, there was a 70%
      decrease in the FBP gene transcription rate and no change in FBP mRNA stability
      in KB1BT cells. Assessing genomic DNA methylation by MspI and HpaII restriction
      analysis suggested that the FBP gene in KB1BT cells was more methylated than in
      KB cells. These alterations in the expression, transcription rate and DNA
      methylation state of the FBP gene did not change when KB1BT cells were grown in
      the absence of MTX for 8 months (MTX-free KB1BT). When MTX-free KB1BT cells were
      exposed to 2.5 microM 5-aza-2'-deoxycytidine for 72 hr, the FBP gene became
      hypomethylated and the levels of membrane-associated FBP and FBP mRNA increased
      by 2- to 3-fold. These data indicate that decreased FBP gene expression in KB1BT
      cells results from increased DNA methylation.

PMID- 7511900
TI  - Desensitization of adenylate cyclase responses following exposure to IP
      prostanoid receptor agonists. Homologous and heterologous desensitization exhibit
      the same time course.
AB  - Pretreatment of NG108-15 cells with 0.03-25 microM prostaglandin E1 (PGE1)
      produced decreases in the maximal stimulation of adenylate cyclase activity
      produced by iloprost, N-ethylcarboxamidoadenosine and sodium fluoride. The rate
      of desensitization to all three agents was dependent on the concentration of PGE1
      used, but at each concentration of PGE1 the rate of loss of responsiveness to
      each agent was the same, suggesting that the decreases in responsiveness may be
      mediated by a single process. Functional desensitization was accompanied by a
      decrease in the specific binding of [3H]iloprost, consistent with a 75-80%
      decrease in IP receptor number, with no change in the coupling of the remaining
      IP receptors to G protein. At each concentration of PGE1 used, the times taken
      for half maximal decreases in receptor number and functional responsiveness were
      similar, suggesting that IP receptor down-regulation is a relatively early event
      in desensitization. IP receptor down-regulation could be inhibited partially by
      100 microM chloroquine, suggesting that lysosomal breakdown of receptors may be
      occurring.

PMID- 7511901
TI  - Pharmacological action of zotepine and other antipsychotics on central 5
      hydroxytryptamine receptor subtypes.
AB  - The effect of the atypical neuroleptic zotepine (CAS 26615-21-4), in comparison
      with clozapine, risperidone and haloperidol, on the responsiveness of different 5
      hydroxytryptamine (5-HT1) receptor subtypes to their agonists was examined in
      rats and mice. The above antipsychotics were investigated in the following
      behavioural tests: 8-OH-DPAT (8-hydroxy-dipropylaminotetralin)-induced
      behavioural syndrome in rats, mCPP (mchlorophenylpiperazine)-induced hypothermia
      in mice and mCPP-induced hypoactivity measured in the open field in rats.
      Zotepine, clozapine and haloperidol did not affect the behavioural syndrome
      induced by 8-OH-DPAT (the selective agonist of 5-HT1A, receptor), only
      risperidone (used in higher doses) attenuated the effect of 8-OH-DPAT. The mCPP
      induced hypothermia in mice (a 5-HT1B effect) was affected by neither zotepine
      nor clozapine, risperidone and haloperidol, all of them used in low doses which
      did not influence per se the body temperature of mice. All the tested
      antipsychotics given at high doses induced hypothermia in control mice; at the
      same time, zotepine, clozapine and risperidone attenuated the hypothermic effect
      of mCPP. mCPP decreases the exploratory activity of rats, this effect being
      considered to be mediated by 5-HT1C receptors. The tested antipsychotics, used in
      low doses, influenced neither the exploratory activity nor the hypoactivity
      induced by mCPP. When used at higher doses, they induced hypoactivity in control
      rats; the hypoactivity after joint administration of zotepine, risperidone or
      haloperidol and mCPP was significantly greater than after mCPP alone, whereas
      clozapine slightly attenuated the effect of mCPP.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7511902
TI  - Effect of minoxidil on the mobility and differentiation of cultivated human
      keratinocytes.
AB  - The mode of topical action of minoxidil (U-10,858, CAS 38304-91-5) ist not
      entirely clear. The influence of minoxidil on the ultimate differentiation of
      keratinocytes was investigated. Human keratinocytes (HaCaT-cells) were incubated
      with minoxidil containing culture medium (10-250 micrograms/ml). Minoxidil
      inhibited in a concentration dependent manner cell mobility whereas the adhesion
      area and the cell circumference were increased. The minoxidil treated cultures
      had a higher desmosome density compared to parallel control cultures and they
      expressed the suprabasal keratins 1 and 10 (indicating progress in
      differentiation) earlier and to a larger extent than the controls. Keratins were
      revealed immunohistochemically and by two-dimensional polyacrylamide gel
      electrophoresis. The results suggest that minoxidil supports the differentiation
      of human keratinocytes.

PMID- 7511903
TI  - Acute effects of deflazacort and its metabolite 21-desacetyl-deflazacort on
      allergic reactions.
AB  - The acute effects of deflazacort (MDL 458, CAS 14484-47-0) and its metabolite, 21
      desacetyl-deflazacort, on allergic reactions in animal models were investigated
      and compared with those of prednisolone. Deflazacort, 21-desacetyl-deflazacort
      and prednisolone all inhibited 48-h homologous passive cutaneous anaphylaxis in
      rats, but had no significant effects on active systemic anaphylaxis in mice, on
      the Schultz-Dale reaction in the isolated guinea-pig trachea or on compound 48/80
      induced histamine release in rat peritoneal mast cells. All three agents
      inhibited reversed cutaneous anaphylaxis in rats and the Arthus reaction in mice.
      The inhibitory effects of deflazacort on the passive cutaneous anaphylaxis, the
      reversed cutaneous anaphylaxis and the Arthus reaction were similar to those of
      21-desacetyl-deflazacort and were stronger than those of prednisolone. Delayed
      type hypersensitivity in mice was also inhibited by deflazacort and 21-desacetyl
      deflazacort, but prednisolone, at the doses used in the present study, had little
      effect on this immune response. These findings indicate that while deflazacort
      and 21-desacetyl-deflazacort have stronger anti-allergic effects than
      prednisolone, they seem to have little acute effect on mast cell degranulation or
      on chemical mediators at the receptor site.

PMID- 7511904
TI  - Functional changes of dextran-modified alkaline proteinase from alkalophilic
      Bacillus sp.
AB  - A serine alkaline proteinase (EC 3.4.21.62) from Bacillus sp. (ALPase I) was
      modified with the 2,4-dialdehyde derivative of clinical dextran (dialdehyde
      dextran). The modified preparation was purified using an ion-exchange column and
      gel filtration. The modified enzyme contained 75% carbohydrate by weight. The
      isoelectric point (pI) of ALPase I was converted from 8.2 to approximately 5.0 by
      this modification. The specific activity of the dextran-modified ALPase I was 56%
      of that of the native enzyme when milk casein was used as a substrate. It also
      had some superior characteristics: the thermostability of the modified enzyme at
      pH 10.0 was about 10-15 degrees C higher than that of control. In organic
      solvents such as n-hexane, benzene, and toluene, the hydrolysis reaction of the
      modified ALPase I for the fluorogenic substrate, succinyl-L-alanyl-L-alanyl-L
      prolyl-L-phenylalanyl-4-methylcoumaryl-7-am ide (Suc-Ala-Ala-Pro-Phe-MCA), was
      several times higher than that of the native. This modification greatly improved
      the stability of ALPase I against nonionic and anionic surfactants. After
      exposure to lauryl benzene sulfonate and sodium lauryl sulfonate the modified
      enzyme retained over 95 and 90% of its activity, respectively, but the native
      enzyme lost its activity. We conclude that modification of serine proteinases
      with dialdehyde-dextran might be a useful method for improving enzyme character
      for enzyme technology.

PMID- 7511906
TI  - [Limits and insufficiencies of the treatments of recent double-break articular
      fractures of the lower fourth of the radius].
AB  - The authors present a series of 39 intra-articular fractures of the distal part
      of the radius classified as Frykman VII and VIII. Clinical results showed 77% of
      good and very good results. Radiographs showed 71% of reduced articular surfaces
      but only 37% of radiuses were considered to be anatomical. The authors emphasize
      the high rate of secondary displacement due to the epiphyseal comminution, and
      the importance of pre-operative radiographs obtained under traction, allowing
      good analysis of the fracture and evaluation of the comminution.

PMID- 7511907
TI  - [Camptodactyly: classification and therapeutic results. Apropos of a series of 50
      cases].
AB  - Fifty patients with camptodactyly of one or several fingers were seen in the
      Strasbourg SOS Main unit between 1980 and 1988. Classification of these lesions
      was based on the mobile or fixed nature of the deformity in flexion of the
      interphalangeal joint. This classification is useful for the therapeutic
      management. Treatment by dynamic splint for a mean duration of 20 months gives
      good results in fixed or mobile camptodactylies of small children, provided that
      this treatment is commenced as soon possible. This splint treatment also obtains
      favorable results in patients reaching the end of the growth period, whether
      their camptodactyly is mobile or even, in some cases, fixed. In every case,
      treatment by dynamic splint constitutes a therapeutic test (safety of the
      apparatus, patient's cooperation) and only forms of camptodactyly resistant to
      conservative treatments benefit from Malek's type of surgical correction. It must
      be remembered that a certain number of cases of camptodactyly have a potential
      for severity with time, progressing towards irreducible forms which can only be
      corrected by surgical treatment. Camptodactyly in adults must be analysed
      meticulously and only major deformities causing functional discomfort or major
      aesthetic prejudice should be operated.

PMID- 7511905
TI  - Upregulation of lineage specific receptors and ligands in multipotential
      progenitor cells is part of an endogenous program of differentiation.
AB  - Multipotent hematopoietic progenitor cell lines (FDCP-Mix) infected with a
      retroviral vector expressing the GM-CSF gene show functional downregulation of
      the GM-CSF receptor when maintained in IL-3 and activation of the receptor
      resulting in synchronous differentiation into mature granulocytes and macrophages
      on withdrawal of IL-3. This system has now been used to investigate whether or
      not receptors for some of the other growth factors are also influenced as a
      consequence of differentiation. We show here the lineage specific receptors for M
      CSF, G-CSF and erythropoietin are all upregulated, regardless of whether or not
      differentiation is induced by GM-CSF or by other conditions. Concomitant
      induction of the mRNA coding for the ligands M-CSF and G-CSF, but not for
      erythropoietin, suggests that M-CSF and possibly G-CSF facilitate macrophage or
      granulocyte differentiation by an autocrine stimulation of the lineage specific
      receptors. FDCP-Mix mutants that are blocked in their ability to differentiate on
      exposure to GM-CSF, but that still require GM-CSF for proliferation, do not
      express increased levels of M-CSF receptor nor M-CSF. Based on these data, we
      suggest that expression of these lineage specific receptors is part of the
      intrinsic endogenous program of myeloid differentiation.

PMID- 7511908
TI  - [The De La Caffiniere trapezo-metacarpal prosthesis in rhizarthrosis of the
      thumb. Apropos of 20 cases surgically treated between 1978 and 1990].
AB  - The authors have studied twenty total prosthesis of de la Caffiniere. These
      prostheses have been inserted between 1980 and 1990 at the "centre de
      Traumatologie et d'Orthopedie de Strasbourg", following a trapezo-metacarpal
      arthritis. According to a post-operative average of five years, the results are
      good in 70% cases. A study of the mobility and of the strength of the hand, as
      well as one of the radiography, allows to make bring out two complications: the
      first, rarely studied for this prosthesis, is a rigidity of the trapezo
      metacarpal articulation due to post-operative ossifications. Consequently the
      post-operative ossifications. Consequently the post-operative benefit decreases
      proportionally to the importance of the rigidity; the second, already pointed out
      in few articles, is the presence of radio lucent lines which is asymptomatic in
      20% of cases. The causes founded are different from the one already published.
      Anyway, in spite of those risks, it is globally useful in the majority of cases.
      Therefore the authors remain loyal to this intervention in the presence of an
      isolated trapezio metacarpal arthritis to the patients with are not subjected to
      handicrafts.

PMID- 7511910
TI  - [Double tunnel syndrome of the upper limb in tophaceous gout. Apropos of a case].
AB  - Association of two tunnel syndromes secondary to tophaceous gout is uncommon.
      This article presents a case of ulnar and carpal tunnel compression. It concerns
      a 71 year old man with gout and treated for that condition. He presented with
      paraesthesiae in the fingers and loss of muscular strength in right hand.
      Physical examination discovered two masses, one in the epitrochlear groove, the
      other in the olecranon bursa; a severe ulnar palsy and a carpal tunnel syndrome.
      Neurolysis of both ulnar and median nerves was performed. After 2 years follow
      up, paraesthesiae disappeared but atrophy of ulnar intrinsic muscles remained
      unchanged. The literature is reviewed. Carpal tunnel syndrome is well known in
      gout (28 reported cases), and is secondary to gouty tenosynovitis. Ulnar tunnel
      syndrome has been described once by Akizuki in 1984. The combination of the two
      conditions has not been previously been reported. In our case, median nerve
      compression was secondary to gouty synovitis but also to a bulky tophus from the
      floor of the carpal tunnel.

PMID- 7511913
TI  - [Palmar dislocation of the metacarpophalangeal joint of the thumb. Apropos of a
      case initially treated by bilateral ligament suture with tendon reinforcement
      surgery].
AB  - We report a case of complete palmar dislocation of the metacarpophalangeal joint
      of the thumb with simultaneous rupture of the radial and ulnar collateral
      ligaments. This highly unstable condition needs a reliable augmentation
      ligamentoplasty which was achieved with a free palmaris longus tendon graft. This
      type of transosseous plasty reinforces the collateral ligaments at their
      anatomical sites. The 7 month end-results is promising: the metacarpophalangeal
      joint remains perfectly stable and painless in spite of a slight residual
      stiffness which causes no discomfort to the patient.

PMID- 7511912
TI  - Free muscle transfer in Volkmann's ischaemic contracture.
AB  - The results of treatment of 28 cases of Volkmann's ischaemic contracture by free
      muscle transfer are presented. Attention is drawn to the existence of an infarct
      in the median nerve in addition to the infarct in the muscle and that loss of
      nerve function is as important as the motor loss in determining functional
      outcome. Comparison of those cases treated early (within 6 months of injury) by
      free vascularised muscle transfer with those operated late showed better sensory
      recovery in the early treated group while the amount of motion obtained was not
      significantly different. Our present indications, timing, and technique of free
      muscle transfer in Volkmann's ischaemic contracture are discussed.

PMID- 7511909
TI  - [Long-term outcome of a silastic semilunar bone prosthesis].
AB  - Eight silastic implants of the lunate bone were inserted between 1980 and 1984 on
      8 patients. Seven patients were seen, at a ten year follow-up visit and were
      satisfied with the results. However, STT osteoarthritis secondary to the carpal
      collapse had to be stabilized by a triscaph arthrodesis. The clinical course
      showed a clear improvement of force and mobility in a first phase, followed by
      progressive deterioration ending in a return to preoperative values. Multiple
      intracarpal cysts were found radiologically in all wrists as well as in the
      distal radius in two cases and in the metacarpal bones in 3 cases. The height of
      the prosthesis was decreased by about 36%. Carpal collapse and ulnar translation
      showed a statistically significant progression. According to these findings,
      silastic prostheses should no longer be recommended.

PMID- 7511914
TI  - [Late flexor synovitis induced by the use of a fabric lace].
AB  - A thirty year old woman underwent trigger finger release of her left middle
      finger after two injections failed to give relief. Several months later, she
      developed an area of nodular tenosynovitis localized to the operative site. Her
      finger had recovered full function, her general health was good, and routine lab
      work was normal. Because of the persistent mass, flexor tenosynovectomy was
      performed. Histologic examination revealed synovial hyperplasia associated with a
      filamentous birefringent foreign material. The bluish color of the foreign
      material indicated that it came from a fabric retraction loop used during the
      original operation. She made an uneventful recovery, and three years later her
      hand remained normal. As a result of this unusual complication, we recommended
      the use of retraction loops made of plastic rather than fabric. Whenever a micro
      foreign body remains in the flexor tendon shealth, there is risk of aseptic
      tenosynovitis.

PMID- 7511915
TI  - [Simplified anesthesia for the surgical treatment of severe sprains of the
      metacarpophalangeal joint of the thumb].
AB  - A series a 40 patients with severe sprain of the medial collateral ligament of
      the metacarpophalangeal joint of the thumb is reported. Anesthesia was performed
      by infiltration of the superficial branch of the radial nerve and the palmar
      collateral nerves of the thumb via of the flexor tendon sheath, with 0.5%
      bupivacaine without adrenaline, 3-4 ml each. This technique, easy and reliable
      (complete success) with a prolonged analgesia, is useful in the operating room
      and for stress examination or dynamic X rays.

PMID- 7511911
TI  - [Plexiform fibrohistiocytic tumor of the hand. Late form].
AB  - Plexiform fibrohistiocytic tumours are very rare, apparently benign neoplasms of
      the superficial soft tissue: only two series and one case report have been
      described in the literature. Macroscopically located within the dermis or
      superficial subcutis, they seem to predominate in the upper limbs of children and
      young adults. Moreover their recurrence rate is relatively high. We report the
      case of a 56 year old male patient presenting such a plexiform fibrohistiocytic
      tumour of the hand, which was surgically excised after a progressive clinical
      evolution of approximately 5 years and in which no recurrence has been observed
      with a follow-up of more than 24 months.

PMID- 7511916
TI  - [The sensory potential of the ring finger. The value of electromyographic
      diagnosis of carpal tunnel syndrome].
AB  - Accurate diagnosis of carpal tunnel syndrome relies on electromyography. The
      usual criteria (sensory conduction velocity and motor latency) fail to identify
      10% of cases of carpal tunnel syndrome. The sensory innervation of the ring
      finger (digit IV) is shared by the median and ulnar nerves. This anatomic feature
      is the basis of a novel electromyographic test: measurement of the sensory
      potential of digit IV by an orthodromic method with stimulation of the finger via
      a ring electrode and recording at the wrist. Analysis of the sensory potential of
      digit IV in 200 subjects with no median nerve compression afforded an invariably
      synchronised trace with no error of interpretation since it required no
      additional measurements. A study of 179 cases in 124 patients suspected of carpal
      tunnel syndrome showed pathological traces that could be graded into five levels
      of severity. Comparison with sensory conduction velocity and distal motor latency
      confirmed its validity and especially its usefulness in mild forms. The
      sensitivity of the test is excellent since false negatives are theoretically due
      to anomalies in the sensory innervation of digit IV, the reported occurrence of
      which varies widely (about 15%). The were no false positives. Its
      reproducibility, painlessness and sensitivity have led us to make this test
      compulsory in all patients suspected of CTS in our practice.

PMID- 7511917
TI  - The influence of color, age, and sex on the content of zinc, copper, nickel,
      manganese, and lead in human hair.
AB  - The hair of 132 healthy subjects between 6 and 40 yr old living in the Veneto
      region in Italy was analyzed by means of HPLC method in order to determine the
      presence of zinc, copper, nickel, manganese, and lead. The collected samples were
      subdivided on the basis of age (6-11 and 19-40 yr), and sex and color (black,
      red, brown, and blond). From the data some evident differences were emphasized.
      In female hair the content of metals was higher than in male hair independently
      of color. Blond hair gave the lowest concentration values of the elements studied
      independently of sex. The maximum amount of the metals was found generally in
      black hair, followed by red and brown hair. Age seems to have a different
      influence, with the copper element decreasing appreciably in brown and blond
      female hair as the age of the subjects increased.

PMID- 7511918
TI  - Impact of lead pollution on the status of other trace metals in blood and
      alterations in hepatic functions.
AB  - Lead pollution and its impact on the status of four other trace elements--Fe, Zn,
      Br, and Rb--have been studied in the whole blood samples of different population
      groups employing energy dispersive X-ray fluorescence technique. These population
      groups included normal, automobile workers and lead battery manufacturers. The
      maximum increase in the concentration of trace elements in the blood samples of
      automobile workers and battery manufacturers was observed for Pb, when compared
      with normal Pb-B levels. The effect of lead pollution had significantly reduced
      Zn levels in automobile workers. Fe-B levels in automobile workers had been found
      to be reduced significantly as compared to control, whereas in battery workers
      the reduction was not significant. The concentration of Br was greatly enhanced
      in the blood samples of automobile workers, whereas Rb-B levels were
      significantly higher in both the automobile and battery workers. Oral
      administration of lead acetate (100 mg/kg body wt) to experimental rats
      significantly decreased the activities of hepatic transaminases after 3 and 4 mo
      of treatment, whereas the activity of hepatic alkaline phosphatase decreased
      significantly after 4 mo of treatment. It is concluded from this study that
      higher Pb-B levels greatly influence the levels of other trace elements in human
      blood samples and also the activities of hepatic transaminases as well as
      alkaline phosphatase in experimental rats.

PMID- 7511919
TI  - Serum copper and zinc levels and copper/zinc ratio in patients with breast
      cancer.
AB  - Serum copper, zinc levels, and the Cu/Zn ratio were evaluated in 31 patients with
      breast cancer and 35 healthy controls. Copper and zinc were determined by atomic
      absorbtion spectrophotometry. The mean serum copper level and the mean Cu/Zn
      ratio in patients with breast cancer were significantly higher than the control
      group (p < 0.001 and p < 0.001). In addition, the mean serum zinc level in
      patients with breast cancer was significantly lower than the control group (p <
      0.001). Neither serum copper and zinc levels nor the Cu/Zn ratio were of value in
      discriminating of the disease activity and severity. Interestingly, the Cu/Zn
      ratio in premenopausal patients was higher than postmenopausal patients (p <
      0.05) and this was not related to age. The further combined biological and
      epidemiological studies are necessary to investigate the roles of copper and zinc
      in breast cancer.

PMID- 7511920
TI  - Concentrations of cadmium, lead, selenium, and zinc in human blood and seminal
      plasma.
AB  - The concentrations of cadmium, lead, selenium, and zinc in blood and seminal
      plasma were determined in 76 Singapore males. Except for zinc, the concentrations
      were generally higher in blood than in seminal plasma (cadmium, 1.31 micrograms/L
      vs 0.61 micrograms/L; lead, 82.6 micrograms/L vs 12.4 micrograms/L, and selenium,
      163.6 micrograms/L vs 71.5 micrograms/L). The mean concentration of zinc in
      seminal plasma was more than 30 times higher than in blood (202 mg/L vs 6.2
      mg/L). Significant positive correlations were found between the concentrations in
      blood and seminal plasma for the two essential trace elements: selenium (r =
      0.45, p < 0.001) and zinc (r = 0.25, p < 0.05). However, no relationships were
      found between the concentrations in blood and seminal plasma for two toxic metals
      (cadmium and lead). Significant inverse correlations were observed between Cd and
      Zn (r = -0.40, p < 0.01), and Pb and Se (r = -0.32, p < 0.05) in blood, whereas
      significant positive correlations were noted between Cd and Se (r = 0.45, p <
      0.01), Cd and Zn (r = 0.35, p < 0.05), and Se and Zn (r = 0.57, p < 0.001) in
      seminal plasma. The physiological significance of these relationships are also
      discussed in this paper.

PMID- 7511921
TI  - Studies on lipid oxidation in fish phospholipid liposomes.
AB  - Fish phospholipid liposomes were prepared and used as an artificial membrane
      system to study factors influencing lipid oxidation. The extent of lipid
      oxidation was indexed by measuring the amount of thiobarbituric acid reactive
      substances (TBARS) produced. Fe2+, Fe3+, and Cu2+ were potent prooxidants in
      catalysing lipid oxidation. These metal ions induced lipid oxidation in a dose
      dependent manner. However, Zn2+, Ni2+, and Mn2+ did not significantly (p > 0.05)
      affect lipid oxidation at all the concentrations (1, 10, or 100 microM) studied.
      Morin, luteolin (flavonoids), butein (chalcone), tannic acid, ellagic acid
      (polyphenols), butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT)
      (synthetic antioxidants) were potent antioxidants (producing < 50% TBARS compared
      to control) of Fe(2+)-catalyzed lipid oxidation. Morin, luteolin, and butein
      possess two hydroxyl substituents, a C4 ketone structure and a 2-3 double bond,
      all of which contributed to their antioxidative potential. Fe2+ caused some
      losses of polyunsaturated fatty acids (PUFA), whereas tannic acid protected the
      oxidation of several of the PUFA including C 16:1 (Palmitoleic acid), C 18:3
      (Linolenic acid), C 20:4 (Arachidonic acid), C 20:5 (Eicosapentaenoic acid), and
      C 22:6 (Docosahexaenoic acid).

PMID- 7511922
TI  - Plasma trace elements concentrations in trained subjects after exposure to
      hypokinesia and daily hyperhydration.
AB  - The objective of this investigation was to evaluate the effect of a daily intake
      of fluid and salt supplementation (FSS) on blood plasma trace elements
      concentrations in physically healthy volunteers after exposure to 364 d of
      hypokinesia (decreased number of steps per day). The studies were performed after
      exposure to 364 d of Hypokinesia (HK) on 30 long-distance runners of volunteers
      who had a VO2 max 67 mL/kg/min and were ranging in the age of 19-24 yrs. Prior to
      their exposure to HK all volunteers were on an average of 10,000 steps/d. For the
      simulation of the hypokinetic effect the volunteers were kept under an average of
      3000 steps/d. All volunteers were divided into three equal groups. The first
      group of volunteers subjected to HK and received daily FSS (water 26 mL/kg body
      wt and sodium chloride 0.16 g/kg body wt.), the second groups of volunteers
      submitted only to HK, and the third group of volunteers underwent a normal
      ambulatory life and served as control. The content of manganese, calcium,
      magnesium, iron, lead, copper, tin, nickel, zinc and cobalamine were determined
      in blood plasma of volunteers. By the end of the hypokinetic period the blood
      plasma concentration of microelements increased significantly in the hypokinetic
      subjects (second group), whereas in the hyperhydrated subjects (first group)
      decreased. It was concluded that prolonged restriction of motor activity induced
      significant increases in blood trace elements concentrations whereas daily
      hyperhydration had a normalizing effect on their concentration in blood plasma.
      This indicates that daily hyperhydration may be used to normalize blood plasma
      concentrations of micro-elements in physically healthy volunteers subjected to
      prolonged restriction of motor activity.

PMID- 7511923
TI  - Effects of albumin and adenosine phosphates on iron transfer from ferric lactate.
AB  - Ferric lactate is known to modify Ca2+ uptake by the cells. To enlighten the role
      of protein and ATP in this phenomenon, iron transfer from ferric lactate to
      albumin and adenosine polyphosphates was determined by electrophoresis. The order
      of iron affinity was ATP > ADP > AMP for the polyphosphates, and albumin does not
      compete for iron binding with the polyphosphates. The iron transfer to ATP was
      also observed in vivo by adsorption chromatography of the adenosine
      polyphosphates fraction from blood plasma of mice injected with ferric lactate
      plus ATP. In vitro iron and calcium uptake by Ehrlich ascites tumor cells showed
      that albumin and ATP decreased iron uptake, whereas calcium incorporation is
      diminished by albumin but augmented by ATP. This difference might be explained by
      albumin binding of ferric lactate that is inhibited from reaching cell
      structures, whereas ATP, known to be an inhibitor of iron polymerization,
      facilitates it.

PMID- 7511924
TI  - Effects of nutritional lithium supplementation on mood. A placebo-controlled
      study with former drug users.
AB  - A total of 24 subjects, 16 males and 8 females, average age 29.4 +/- 6.5 y, were
      randomly divided into two groups. Group A received 400 micrograms/d of lithium
      orally, in tablets composed of a naturally lithium-rich brewer's yeast, for 4 wk.
      Group B was given normal, lithium-free brewer's yeast as a placebo. All the
      subjects of the study were former drug users (mostly heroin and crystal
      methamphetamine). Some of the subjects were violent offenders or had a history of
      domestic violence. The subjects completed weekly self-administered mood test
      questionnaires, which contained 29 items covering parameters measuring mental and
      physical activity, ability to think and work, mood, and emotionality. In the
      lithium group, the total mood test scores increased steadily and significantly
      during the period of supplementation. The 29 items were furthermore placed into
      three subcategories reflecting happiness, friendliness, and energy, as well as
      their negative counterparts. In Group A, the scores increased consistently for
      all subcategories until wk 4 and remained essentially the same in wk 5. In Group
      B, the combined mood test scores showed no consistent changes during the same
      period. The only positive change in some members of Group B occurred during wk 1
      and was attributed to a placebo effect. In Group B, the placebo effect was
      noticeable for the subcategories of energy and friendliness; the happiness scores
      declined during the entire period of observation. Based on these results and the
      analysis of voluntary written comments of study participants, it is concluded
      that lithium at the dosages chosen had a mood-improving and -stabilizing effect.

PMID- 7511925
TI  - Heme oxygenase induction. A possible factor in aluminum-associated anemia.
AB  - The effect of repeated parenteral administration of aluminum (Al) was
      investigated to determine if a relationship exists between the severity of anemia
      and increase in hepatic heme oxygenase activity. Female Swiss Webster mice were
      dosed for 11 d with 50 mg Al/kg, as Al lactate, and sodium lactate was given to
      control mice. On d 12, hematocrit, hemoglobin, blood smears, hepatic heme
      oxygenase activity, and cytochrome P450 levels were assessed. Significant
      decreases in hematocrit (39.1 +/- 0.7 vs 43.1 +/- 0.3% in controls) and
      hemoglobin (13.1 +/- 0.4 vs 14.2 +/- 0.2 g/dL in controls) were produced by Al
      administration. Blood smears from Al-treated mice consistently showed smaller,
      more irregular red cells. Cytochrome P450 content was significantly decreased
      (0.443 +/- 0.043 vs 0.665 +/- 0.055 nmol/mg) whereas hepatic heme oxygenase
      activity was significantly increased (2.75 +/- 0.34 vs 1.66 +/- 0.20 nmol/mg/h)
      in Al-treated animals. The production of mild anemia by parenteral aluminum
      correlated significantly with the increase in heme oxygenase activity, which,
      although only 66% greater than in control, preceded a significant loss of
      cytochrome P450. The increased heme oxygenase activity, with subsequent increased
      destruction of heme and/or heme proteins is discussed as a possible mechanism for
      the microcytic, hypochromic anemia associated with Al overload.

PMID- 7511926
TI  - Quantitative and 3-dimensional analysis of Langerhans cells in basal cell
      carcinoma. A comparative study using light microscopy and confocal laser scanning
      microscopy.
AB  - We have analysed Langerhans cells (LCs) in basal cell carcinoma (BCC) and in
      healthy skin in 15 patients, using three different techniques: light microscopic
      examination of horizontal sheets, and of 6-micron-thick vertical skin sections,
      and confocal laser scanning microscopy (CLSM) of 25-micron-thick vertical
      sections. The use of CLSM enables both a quantitative and a three-dimensional (3
      D) analysis of the cells in the same tissue volume. A statistically significant
      reduction in the relative volume of epidermal CD1a reactivity confined to tumour
      areas was found with CLSM. This difference was confirmed when the number of LCs
      in horizontal sheets were counted. In contrast, no significant reduction in
      epidermal CD1a+ cells was found in thin vertical sections. This is probably due
      to the smaller tissue sample examined, and to variations in the number of CD1a+
      cells, with less cells directly overlying the tumour nests. The ratio of CD1a
      expressing cells in the epidermis/dermis was significantly reduced in BCCs,
      compared with healthy looking skin. Few LCs were observed in tumour nests, but
      they were numerous in the surrounding stroma of the dermis. Three-dimensional
      reconstructions of CD1a+ cells in BCC revealed striking morphological changes;
      they had a reduced number of dendrites, and these were often short and had few
      branches. The results demonstrate that CLSM is a suitable technique for
      quantitative and morphological analysis of CD1a-expressing cells in the skin. We
      suggest that the alterations in LC numbers, distribution and morphology in BCC
      most probably are secondary to changes in the local environment.

PMID- 7511927
TI  - Disruption of the determinant hierarchy on a self-MHC peptide: concomitant
      tolerance induction to the dominant determinant and priming to the cryptic self
      determinant.
AB  - The presentation of self-peptides in a self-restricted manner plays a critical
      role in the complex positive and negative selective process of T cell recognition
      of self-determinants. The population of determinants comprises (i) a dominant set
      which is efficiently presented and induces clonal elimination or inactivation of
      the corresponding autoreactive T cells, and (ii) a cryptic set which is not
      processed efficiently enough to reach the threshold of presentation to make an
      impact on the T cell repertoire during thymic selection. Here we have studied a
      self-MHC peptide, Ld 61-85, which as shown in earlier work was able to induce
      vigorous T cell proliferation in syngeneic animals. Despite the fact that this
      peptide as a whole is 'cryptic', the fine specificity of the class II restricted
      response was complex, in that there were three distinct and overlapping T cell
      determinants: the dominant determinant, Ld 65-80, flanked by two cryptic
      determinants, Ld 61-75 and Ld 73-85, all of which compete for stimulating in vivo
      autoreactive T cell proliferative responses. The hierarchy of these determinants
      bears an interesting relationship to tolerance. Ld 61-85 or Ld 61-80 priming
      induces proliferation only to Ld 65-80; likewise, tolerance induction to Ld 61-80
      prevents elicitation of a subsequent response to Ld 61-80 or Ld 65-80 in the
      local lymph nodes. However, in the Ld 61-80 tolerant mice, in vivo challenge with
      Ld 61-80 induces a strong T cell proliferative response directed towards cryptic
      Ld 61-75.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511928
TI  - CD44 isoform expression mediated by alternative splicing: tissue-specific
      regulation in mice.
AB  - CD44 is a widely distributed cell surface glycoprotein which shows heterogeneity
      in molecular expression as a result of post-translational modification as well as
      alternative splicing of CD44 mRNA. Functional studies have indicated that CD44
      plays a role as an adhesion molecule and that different CD44-expressing cells
      differ in their capacities for CD44-dependent ligand binding. These observations
      have raised the possibility that structural modifications of CD44, including
      those resulting from alternatively spliced mRNA isoforms, are involved in the
      functional heterogeneity of CD44. To assess the expression of CD44 isoforms in
      the mouse, we examined CD44 cDNA by reverse transcription polymerase chain
      reaction (RT-PCR). Southern blotting of PCR products with a CD44 cDNA probe or
      with internal oligonucleotides revealed the expression in mouse tumor cell lines
      and normal tissues of multiple CD44 mRNA products which are larger than that
      observed in the absence of variable exon expression. Interestingly, different
      mouse tissues, including lymphoid cells, showed unique patterns of alternative
      CD44 mRNA in Southern blotting analysis. The use of exon-specific primers allowed
      detection of multiple alternatively spliced mRNA species involving expression of
      at least seven variable exons. Cloning and sequencing of these PCR products
      revealed sequence identity with recently identified genomic CD44 sequences and
      confirmed that the PCR products correspond to mature mRNA expressing
      alternatively spliced CD44 exons. Taken together, these findings demonstrate that
      the mouse expresses multiple variably spliced CD44 isoforms and that expression
      is regulated in a tissue- and cell-type specific manner.

PMID- 7511929
TI  - The onset of Fas expression parallels the acquisition of CD8 and CD4 in fetal and
      adult alpha beta thymocytes.
AB  - Fas is an apoptosis-related cell surface molecule whose defective transcription
      results in the lpr defect and autoimmunity. Recent analysis of Fas mRNA and
      protein expression in normal mice showed high expression in the thymus, on
      activated T cells, and on 5-10% of peripheral T cells. To investigate the role of
      Fas in the thymus, we analyzed its expression in fetal and adult thymocyte
      subsets. Fas was not expressed on fetal nor adult CD8-CD4- (double-negative, DN)
      T cell precursors. The earliest precursors that expressed low levels of FAS were
      the immediate precursors of DP thymocytes that bear the CD44-CD25-CD8loCD4loTCRlo
      phenotype. Other DN cells that expressed Fas appeared to be either non-T cells or
      mature alpha beta + DN thymocytes. The onset of Fas expression followed the onset
      of expression of CD8 and CD4 and Fas expression reached its peak in CD8+CD4+
      double-positive (DP) thymocytes. Both single-positive (SP) subsets were largely
      Fas+ (CD8 SP < CD4 SP) but expressed lower levels of Fas than DP cells. However,
      a majority (> 60%) of the most mature HSA(lo) SP cells (2-5% of all SP
      thymocytes) were Fas- and the remainder of the HSA(lo) SP cells was Fas(lo). We
      observed two main differences between Fas expression on fetal versus adult
      thymocytes. First, up to 90% of fetal gamma delta + DN cells expressed high
      levels of Fas, in contrast to the very low expression (< 7% Fas+ cells) among
      adult gamma delta + thymocytes. Second, whereas virtually all adult DP cells were
      Fas+, up to 75% of fetal day 16 DP cells were Fas-.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7511930
TI  - Bovine gamma delta T cells express high levels of functional peripheral lymph
      node homing receptor (L-selectin).
AB  - Lymphocyte migration from the blood into specific tissues is directed by their
      expression of adhesion molecules referred to as homing receptors. The homing
      receptor L-selectin, for example, directs the migration of lymphocytes into
      peripheral lymph nodes (PLN). Since bovine gamma delta T cells, a major
      lymphocyte subset in peripheral blood (25-50%), represent only a minor subset in
      PLN, we examined whether these cells lack expression or function of L-selectin.
      We found that bovine gamma delta T cells expressed L-selectin at levels higher (2
      to 5-fold) than alpha beta T cells and B cells. Furthermore, gamma delta T cells
      accumulated along the vascular wall of venules that support lymphocyte
      extravasation into PLN (MECA-79+ venules) in vivo and bound mouse PLN high
      endothelial cell venules in an ex vivo binding assay. In contrast to this primary
      adhesive event, we directly demonstrate that gamma delta T cells in vivo do not
      appreciably extravasate from the blood into the parenchyma of lymph nodes. Since
      the lack of functional L-selectin expression could not account for the inability
      of gamma delta T cells to enter PLN, we tested for other differences between
      gamma delta T cells and PLN homing lymphocytes related to the processes following
      primary adhesion; for instance, the down-regulation of L-selectin expression
      following short-term activation and the expression of accessory adhesion
      molecules necessary for transendothelial migration. We found that gamma delta and
      alpha beta T cells demonstrate differential down-regulation of L-selectin after
      PMA activation. Kinetic analysis revealed that, at all time points after PMA
      treatment, L-selectin expression remained significantly higher on gamma delta T
      cells and was down-regulated at a slower rate compared with alpha beta T cells.
      However, the expression levels of CD44 and CD18 on gamma delta and alpha beta T
      cells were found to be equivalent. This study is the first to demonstrate for
      lymphocytes that the expression of L-selectin alone does not predict a PLN homing
      capacity. Our results suggest that the gamma delta T cells' reduced ability to
      enter PLN may be due to inefficient down-regulation of L-selectin compared with
      non-gamma delta lymphocytes, thus potentially disrupting the dynamics of the
      extravasation event.

PMID- 7511931
TI  - Suppression of allograft responses by combining alloantigen-specific i.v. pre
      sensitization with suboptimal doses of rapamycin.
AB  - C57BL/6 (B6) mice were injected i.v. with class I H-2-disparate B10.QBR spleen
      cells (10(7)/mouse). This regimen, termed donor alloantigen-specific i.v. pre
      sensitization (DSP), induced almost complete reduction of the anti-B10.QBR mixed
      lymphocyte reaction (MLR) that has been regarded to represent a cytotoxic T
      lymphocyte (CTL)-independent graft rejection pathway. Because the DSP regimen
      failed to affect the generation of CTL responses, it did not prolong graft
      survival. Repeated (four or 11 times) administration in vivo (during 5 or 18
      days) of rapamycin at suboptimal doses (0.5-2.0 mg/kg/day) failed to eliminate
      the capacities to exhibit MLR as well as to generate CTL responses. The
      suppression of CTL responses was achieved only through the combination of these
      two treatments. It was also shown that prolongation of skin graft survival was
      not induced by either of a single DSP or rapamycin treatment alone, but by the
      combination of these. Potent suppression of CTL responses was also induced when a
      single DSP was combined with repeated injection of a suboptimal dose (0.75
      mg/kg/day) of another immunosuppressive drug, FK506, instead of rapamycin.
      However, there was a substantial difference in cellular mechanisms underlying the
      suppression of CTL responses by the above two different combinations. Under
      conditions in which lymphoid cells from mice receiving the treatments with DSP
      plus FK506 failed to generate CTL responses, the addition of recombinant IL-2
      (rIL-2) to cultures restored the CTL generation, suggesting that CTL precursors
      themselves are not attenuated by the combined treatment.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7511932
TI  - Cytokeratin-containing cells in proliferative diabetic retinopathy membranes.
AB  - Immunohistochemical techniques were used to investigate the relation between
      retinal pigment epithelial cells (RPE), traction retinal detachment (TRD)
      membranes, and combined traction rhegmatogenous retinal detachment (CTR)
      membranes in proliferative diabetic retinopathy. Seven CTR and five TRD membranes
      were obtained during closed microsurgery. Six of the seven CTR membranes and one
      of the five TRD membranes contained RPE. Eleven of the 12 diabetic membranes
      incorporated glial cells. The findings emphasise that the intravitreal membranes
      of proliferative diabetic retinopathy contain a diversity of cell types and
      indicate that RPE tend to contribute to CTR, rather than TRD, membranes. The
      histopathological appearance of CTR membranes is that of a hybrid between TRD and
      proliferative vitreo-retinopathy membranes.

PMID- 7511933
TI  - ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis.
      Demonstration of oxidation-specific epitopes in lesions and high titers of
      autoantibodies to malondialdehyde-lysine in serum.
AB  - Apolipoprotein (apo) E-deficient transgenic mice develop marked hyperlipidemia
      and progressive atherosclerotic lesions. To explore whether oxidative
      modification of lipoproteins is involved in atherogenesis in this murine model,
      we performed extensive immunocytochemical studies. Atherosclerotic lesions
      ranging from early fatty streaks to very advanced plaques were examined from the
      aortic valve region and the thoracic and abdominal aorta. Using guinea pig
      antisera against malondialdehyde (MDA)-lysine and 4-hydroxynonenal-lysine, two
      epitopes generated during the oxidative modification of low-density lipoprotein
      (LDL), we demonstrated the presence of these "oxidation-specific epitopes" in
      atherosclerotic lesions. In early lesions, oxidation-specific epitopes were found
      predominantly in macrophage-rich areas, whereas diffuse extracellular staining
      predominated in necrotic areas of advanced lesions. We have previously shown that
      autoantibodies against MDA-lysine are present in the circulation of humans and
      rabbits and that the immunoglobulin fraction extracted from their lesions
      contains autoantibodies against several "oxidation-specific" epitopes. Sera from
      apoE-deficient mice also contained circulating autoantibodies to MDA-lysine, and
      both early and advanced lesions were rich in murine immunoglobulins. Titers of
      serum autoantibodies were significantly higher in apoE-deficient mice than in
      C57BL/6 mice. Autoantibodies in murine plasma recognized MDA-lysine epitopes in
      atherosclerotic lesions of rabbits, and the immunostaining was competitively
      inhibited by excess human MDA-LDL. Similar findings were obtained by competitive
      radioimmunoassay. Finally, a morphometric technique was developed and tested in
      these mice that allows a quantitative assessment of aortic atherosclerosis. These
      findings suggest that in apoE-deficient mice, lipoprotein oxidation is involved
      in atherogenesis and that these transgenic mice constitute an appropriate model
      with which to study the antiatherogenic effect of antioxidant intervention.

PMID- 7511934
TI  - CD 34 immunotyping of blasts in myelodysplasia.
AB  - We studied the expression of the hematopoietic progenitor cell antigen CD 34 in
      six patients with refractory anemia with excess of blasts (RAEB), five patients
      with RAEB in transformation (RAEB-T), and seven patients with chronic
      myelomonocytic leukemia (CMML). Immunocytochemical labeling of bone marrow cells
      was performed by an indirect immunoperoxidase method with preservation of
      morphological details. The cells were stained with May-Grunwald-Giemsa,
      photographed, destained, and immunolabeled by the immunoperoxidase technique. We
      found 1.5 +/- 0.5% blasts and 0.8 +/- 0.4% CD 34+ blasts in normal bone marrow.
      The CD 34 positivity of blasts was 53 +/- 9%. The patients with RAEB showed 1.7
      +/- 1.4% CD 34+ blasts. The CD 34 positivity of blasts (11.8 +/- 5.6%) was lower
      than in normal bone marrow. The patients with RAEB-T had a higher percentage of
      CD 34+ blasts (7.3 +/- 3.4) and a higher CD 34 positivity of blasts (28.2 +/-
      14.6%) than patients with RAEB. The CMML patients showed a percentage of CD 34+
      blasts and a CD 34 positivity of blasts in the range of RAEB. We found an
      increase of promonocytes (PMC) in 5/7 patients. In some patients the PMC were CD
      34 positive. Our results indicate that the increase of blasts in REAB is related
      to CD 34-negative blasts. With progression to RAEB-T the percentage of CD 34
      positive blasts increased. Some of the CMML patients also showed a population of
      CD 34-positive PMC. A clone of undifferentiated CD 34-positive cells is
      characteristic for patients with these types of myelodysplasia.

PMID- 7511935
TI  - Differences of E-cadherin expression levels and patterns in human lung cancer.
AB  - Fifty-two lung carcinomas obtained at surgical resection were examined by
      immunofluorescence for their expression levels and patterns of the calcium
      dependent intercellular adhesion molecule E-cadherin. In well-differentiated
      squamous cell and adenocarcinomas expression of E-cadherin was confined to the
      lateral cell border, similar to the expression level and pattern of normal lung
      tissue. The E-cadherin level was reduced and the expression pattern was spotty or
      diffuse in moderately and poorly differentiated squamous cell carcinomas and in
      small cell carcinomas of the lung. Also, most metastases resected had a reduced
      level and an altered pattern of E-cadherin expression. In contrast, no such
      correlation was found in adenocarcinomas of the lung. This indicates that
      different cellular mechanisms are responsible in the progression of squamous cell
      carcinomas versus adenocarcinomas of the lung.

PMID- 7511936
TI  - In patients with BCR-ABL-positive ALL in CR peripheral blood contains less
      residual disease than bone marrow: implications for autologous BMT.
AB  - Residual leukemic cells are detectable at frequencies as low as 1 in 10(6) normal
      cells in patients with Philadelphia chromosome/BCR-ABL-positive leukemias in
      complete remission (CR) using reverse-transcriptase polymerase chain reaction (RT
      PCR) with specific nested primers. The level of minimal residual disease (MRD) in
      the bone marrow (BM) and the peripheral blood (PB) may favor one of the two as
      the source for an autologous graft. In order to quantify MRD with RT-PCR we
      analyzed patients ficolled cells after limiting logarithmic dilutions in normal
      ficolled buffy-coat cells. In six patients with BCR-ABL-pos ALL who were in CR by
      conventional criteria (5 in CR1 and 1 in CR2), we studied a total of nine paired
      BM and PB samples prior to scheduled ABMT. A positive RT-PCR signals was
      detectable in all samples up to dilutions ranging from 1:10(1) to 1:10(3) in PB,
      and at higher titers ranging from 1:10(3) to 1:10(5) in the BM. The BM titers
      exceeded the corresponding PB titers in all nine sample pairs by at least 1 log.
      The mean difference was 1.55 log (geometric mean, n = 9) and is statistically
      significant (p < 0.03). We conclude that residual leukemia in BCR-ABL-positive
      ALL preferentially locates in the BM compartment, and we assume that PB may yield
      autologous grafts with significantly less leukemic contamination.

PMID- 7511938
TI  - Permeabilization, staining and culture of living Drosophila embryos.
AB  - The organic solvent octane has been used routinely to permeabilize the
      hydrophobic vitelline membrane surrounding the Drosophila embryo, thereby
      allowing the movement of small molecules into the egg. We present evidence that
      hexane is a more effective permeabilizing agent than octane and compare the
      effects of these solvents on uniformity of permeabilization and embryonic
      viability. The ability of each solvent to make the embryo accessible to a range
      of biological stains was compared. The effect of octane versus hexane
      permeabilization on subsequent embryonic viability was measured at seven
      different stages during early embryogenesis. We found that although hexane is a
      superior solvent for permeabilizing the vitelline membrane, it decreases the
      viability of embryos exposed between 0 and 3 hr of age. Older embryos treated
      with either hexane or octane are usually viable. We also showed that molecules
      with a molecular mass of 984 Daltons or more did not diffuse into the embryo
      following treatment with either hexane or octane. Results presented here
      challenge a phase-partition model that has been proposed previously to explain
      the molecular basis of permeabilization of the Drosophila egg. An alternative
      model is described as well as an optimized protocol for permeabilizing and
      staining Drosophila embryos at any stage during early embryogenesis while
      maintaining viability for subsequent culture.

PMID- 7511937
TI  - Standardization of staining in glycosaminoglycan histochemistry: alcian blue, its
      analogues, and diamine methods.
AB  - Glycosaminoglycans are identified in tissue sections by various histochemical
      techniques including staining with alcian blue and its analogues, such as
      cuprolinic blue and cupromeronic blue, or with high and low iron diamine methods.
      The variation in staining results in particularly confusing in the case of alcian
      blue, where not only are several different brands of alcian blue available but
      also several different staining protocols are used. If the results obtained by
      these techniques are compared, they often do not match. We have developed a dot
      blot technique for quality control of glycosaminoglycan histochemistry to
      standardize the staining protocols. This staining technique enables histochemists
      to test particular batches of alcian blue or its analogues for selective
      glycosaminoglycan staining, thus improving control of histochemical results. The
      results obtained using the dot blot assay indicate that it is necessary to test
      each batch of dye individually to obtain valid results in glycosaminoglycan
      histochemistry.

PMID- 7511940
TI  - Improving biological dyes and stains: quality testing versus standardization.
AB  - This paper discusses the impact of both standardization and quality testing of
      dyes and stains in biology and medicine. After the brief review of why
      standardized dyes and strains are not presently available commercially, two types
      of testing and ways of improving dye quality are described. National or
      international organizations could be established to define standardization of
      dyes and stains. Standardization would be specifically defined as a list of
      physico-chemical parameters such as elaborated in this paper. Commercial batches
      of comparable quality may be labeled by the supplier as "standard dye," a
      procedure currently performed by the European Council for Clinical and Laboratory
      Standardization (ECCLS). Also recommended to improve dye quality is commercial
      dye testing by independent laboratories with subsequent certification for use.
      This sort of quality control is currently carried out in the United States by the
      Biological Stain Commission (BSC). The advantages and disadvantages of both
      techniques and the use of image analysis for the definition of standards are
      discussed. A combination of both the BSC testing protocols and the ECCLS
      standards should be established for extended quality control of biological dyes
      and stains.

PMID- 7511941
TI  - Role of granulocyte colony-stimulating factor in the immune response to acute
      bacterial infection in the nonneutropenic host: an overview.
AB  - Granulocyte colony-stimulating factor (G-CSF) regulates the production and
      potentiates the function of neutrophils. Studies of animals and patients have
      shown that levels of G-CSF increase in response to certain types of acute
      bacterial infection; for example, levels of this factor increase in the lungs and
      in serum during pneumonia. Investigations of several nonneutropenic animal models
      of severe bacterial infection have indicated that exogenous recombinant G-CSF-
      either alone or in combination with antibiotics--can significantly enhance host
      defenses and improve rates of survival. Trials of recombinant G-CSF for the
      prevention or treatment of serious infection in clinical settings have recently
      been initiated.

PMID- 7511939
TI  - Restoring and immunohistological examination of Feulgen stained avian embryonic
      tissues using iron hematoxylin and endothelial cell specific antibody.
AB  - The immunohistological method described here permits re-examination of previously
      Feulgen stained quail-chick chimera tissues for vascular development using the
      monoclonal antibody QH1 which specifically recognizes quail hemangioblastic
      cells. Weigert's iron hematoxylin has been used to restore faded or bleached
      Feulgen stained chimeric avian tissues. Species-specific differences in nuclear
      morphology are as evident with iron hematoxylin staining as they are with Feulgen
      staining.

PMID- 7511942
TI  - The nitric oxide synthase family of proteins.
AB  - Nitric oxide (NO) is an important bio-regulatory molecule in the nervous, immune
      and cardiovascular systems. NO is synthesized from one of the guanidino nitrogens
      of L-arginine by the enzyme nitric oxide synthase (NOS). To date, several
      isoforms of NOS have been purified and cloned. These proteins represent a novel
      family of mammalian enzymes that contain both heme and cytochrome P450 reductase
      domains. The three prototypical forms of NOS: neuronal, cytokine-inducible and
      endothelial NOS, are derived from separate genes and are regulated by diverse
      signaling pathways. The purposes of this review are to highlight recent advances
      in the enzymology and molecular biology of this important family of proteins and
      to examine how this information pertains to the regulation of NO production.

PMID- 7511943
TI  - Downregulation of endothelial cell thrombospondin 1 enhances in vitro
      angiogenesis.
AB  - Vascular endothelial cells are an established source of thrombospondin 1 (TSP1),
      a multifunctional extracellular matrix molecule. TSP1 appears to play an
      important role in modulating endothelial cell functions such as proliferation,
      migration, and capillary morphogenesis. In addition, TSP1 has recently been
      reported to potently inhibit angiogenesis both in vitro and in vivo. To better
      understand the mechanism underlying the antiangiogenic property of TSP1,
      endogenous TSP1 production was disrupted in bovine aortic endothelial cells
      (BAEC) by stable transfection with a vector expressing a TSP1 antisense RNA.
      Stable transfectants in which the antisense vector caused a decrease in TSP1
      production were assayed for their ability to form capillary-like cords on gelled
      basement membrane matrix and for their responsiveness to the
      angiogenic/chemotactic mediator basic fibroblast growth factor. BAEC in which
      TSP1 production was disrupted exhibited a ten-fold increase over control BAEC in
      chemotactic activity to basic fibroblast growth factor and a twofold increase
      over control cells in the number of capillary-like cords that formed on gelled
      basement membrane matrix. Thus, the down-regulation of endogenous TSP1 appears to
      facilitate endothelial cell chemotaxis and capillary morphogenesis. These studies
      suggest that the modulation of TSP1 production is an important component of the
      angiogenic response, and support the idea that soluble TSP1 inhibits angiogenesis
      by interfering with endothelial cell chemotaxis and capillary formation.

PMID- 7511944
TI  - Cross-linking of alpha 2-antiplasmin to fibrin is a key factor in regulating
      blood clot lysis: species differences.
AB  - The basal lysis rates of ex-vivo prepared blood clots from rats, mice, hamsters,
      dogs, and humans and levels of alpha 2-antiplasmin (alpha 2-AP) cross-linked to
      fibrin have been studied in the presence and absence of factor XIII (FXIII)
      inhibitors using a blood clot lysis assay and an alpha 2-AP binding assay. Clots
      prepared from rat or human blood lysed spontaneously within 3-5 h. Clots from
      hamster blood lysed completely within 30 min but clots prepared from murine or
      canine blood lysed only after addition of 1.0 IU human t-PA. To study the effect
      of activated FXIII (FXIIIa) inhibition on blood clot lysis the FXIII inhibitors
      L722151 and mono-dansylcadaverine (dansyl) were used. In the presence of the
      FXIII inhibitors human, murine, and canine blood clots showed increased lysis
      rates. The lysis rate of rat blood clots was not affected. Effects on hamster
      blood clots could not be detected because of the high basal lysis rate. In clots
      prepared from human, murine, or canine plasma about 20% of the plasma alpha 2-AP
      concentration was cross-linked to fibrin. FXIII inhibitors inhibited cross
      linking by more than 80%. No significant cross-linking of alpha 2-AP could be
      detected in rat and hamster plasma clots. When 0.1 volume of human plasma was
      added to 0.9 volume of rat plasma the level of alpha 2-AP cross-linking was equal
      to that in human plasma indicating that rat alpha 2-AP can be cross-linked to
      human fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511945
TI  - Time course of clotting and fibrinolytic markers in acute upper gastrointestinal
      bleeding: relation to diagnosis and blood transfusion treatment.
AB  - One hundred consecutive patients with acute upper gastrointestinal bleeding were
      investigated. Blood coagulation and fibrinolytic activity were monitored by
      levels of plasma thrombin-antithrombin III (TAT) complex and plasmin-alpha 2
      antiplasmin (PAP) complex in samples obtained from patients at admission with
      haematemesis and/or melana and in samples obtained from patients the first day
      after admission. Blood was transfused according to a restrictive policy. Median
      plasma TAT complex was significantly elevated both at admission and on the first
      day after admission compared with a reference group. Plasma PAP complex levels
      were normal at admission but decreased on the first day after admission. This
      decrease was independent of blood transfusion. The results indicate
      hypercoagulability at admission among patients with upper gastrointestinal
      haemorrhage reinforced by the development of a hypofibrinolytic state during the
      first day after admission. Restricted blood transfusion was not associated with
      any detectable change in blood coagulation or fibrinolysis in these patients.

PMID- 7511946
TI  - Different responses of human marrow and circulating erythroid progenitors to stem
      cell factor, interleukin-3 and granulocyte/macrophage colony-stimulating factor.
AB  - The effects of recombinant human stem cell factor (SCF/c-kit ligand), interleukin
      3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) on
      erythroid colony formation by non-phagocytic mononuclear cells (MNC) and CD34+
      cells derived from normal human bone marrow (BM), peripheral blood (PB) and
      umbilical cord blood (CB) were studied using a methylcellulose culture containing
      recombinant human erythropoietin (Epo). BM-MNC generated the largest number of
      total erythroid colonies consisting of erythroid bursts and erythroid mixed
      colonies (E-Mix) in the presence of SCF, whereas PB-MNC produced the largest
      number with IL-3. No additive effect between SCF and IL-3 was observed in the
      erythroid colony formation by BM- or PB-MNC. These observations were reproducible
      in cultures with several independent samples and purified CD34+ cells, suggesting
      that in normal human adults the erythroid progenitors supported by SCF alone
      mainly reside in the BM but those supported by IL-3 alone are mainly circulating.
      IL-3 was the most potent promoter of the total erythroid colony formation by CB
      MNC, but it had no cooperation with SCF. In contrast, SCF supported large numbers
      of E-Mix and showed significant cooperative activity with IL-3 in E-Mix
      formation. These findings were also confirmed using independent specimens and
      CD34+ cells. Outstanding E-Mix formation by the CB cells indicated that newborn
      infants contain significantly more immature circulating erythroid progenitors
      than adults. These observations will stimulate interest in the role of the c-kit
      SCF system as an adhesion molecule in the ontogenetic development of hemopoiesis.

PMID- 7511947
TI  - Granulocyte colony-stimulating factor enhances the expression of CD62 on
      platelets in vivo.
AB  - The expression of CD41, CD42 and CD62 on platelets was determined in ten patients
      with and without G-CSF treatment. CD41 and CD42 is expressed in nearly 100% of
      the platelets without change after G-CSF treatment. The expression of CD62 on the
      platelets' surface is significantly enhanced by G-CSF indicating a depletion of
      the alpha-granules. No platelet aggregation was observed. The enhanced secretion
      of thrombocyte-specific proteins does not induce aggregation but may promote ADP
      induced aggregation. Furthermore, the surface-bound and soluble CD62 binds
      specifically to macrophages and endothelial cells and is involved in the
      regulation of inflammatory processes. Thus indirect mechanisms may supplement
      direct effects of G-CSF after chemotherapy.

PMID- 7511948
TI  - Ascending aorta to right pulmonary artery interposition shunt in critically ill
      infants.
AB  - In spite of a trend toward earlier complete repair, some neonates and infants
      with complex cyanotic heart disease continue to require interim palliation with
      systemic-to-pulmonary artery shunts. A variety of shunt procedures have been
      proposed, each with inherent advantages and disadvantages. We have found a
      prosthetic interposition shunt between the ascending aorta and right pulmonary
      artery (AA-RPA) to be effective in very young infants with small vessels. Over a
      15-year period, 51 patients, mean weight 3.33 kg and mean age 59 days, underwent
      this procedure with a 13% perioperative mortality and a 78% 2-year overall shunt
      patency rate. We conclude that the AA-RPA interposition shunt is a safe,
      effective procedure in these infants.

PMID- 7511949
TI  - Isbufylline, a xanthine derivative, inhibits bronchoconstrictor responses
      produced by stimulation of capsaicin-sensitive sensory nerves in guinea-pig: 'In
      vitro' and 'in vivo' evidence.
AB  - Isbufylline (1,3-dimethyl-7-isobutylxanthine) is a new xanthine derivative
      claimed to possess remarkable antibronchospastic properties coupled to reduced
      pro-convulsive side-effects. In guinea-pig bronchial preparations, isbufylline
      showed a differential and more pronounced, as compared to theophylline, relaxant
      activity on tonic bronchial contractions evoked by exogenous administration of
      equieffective concentrations of capsaicin (0.3 microM), neurokinin A (0.1 microM)
      and carbachol (0.3 microM) (in the presence of indomethacin 5 microM and
      thiorphan 10 microM). Isubfylline gave an IC50 of 21 (19-25, 95% confidence
      limits) microM on capsaicin-evoked contractile effects, and 36 (30-43) microM on
      carbachol-produced contractile effects, whilst it was almost ineffective in
      inhibiting neurokinin A-induced bronchospasm (IC50 not evaluable, > 100 microM).
      'In vitro' studies were also performed using electrical field stimulation (EFS)
      to produce non-adrenergic non-cholinergic (NANC)- or cholinergic nerves-mediated
      contractions in guinea-pig isolated bronchi or trachea. Isbufylline (10-90
      microM) produced a concentration-dependent inhibition of the NANC response (EFS:
      20 Hz, supramaximal voltage, 0.5 ms pulse, width for 10 s) of bronchi (IC50 = 47
      microM) without affecting the cholinergic contractile response in tracheal smooth
      muscle (EFS: 0.5 up to 32 Hz, supramaximal voltage, 0.5 ms pulse, for 15 s every
      min). The activity of isbufylline was also confirmed in anaesthetized guinea-pig
      showing a greater antibronchospastic activity towards capsaicin (8 nmol/kg i.v.)
      or vagal non-cholinergic (10 V, 1 ms, 20 Hz for 20 s) stimulation as compared to
      the inhibition exerted against acetylcholine (50 nmol/kg i.v.) or neurokinin A (1
      nmol/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511951
TI  - [Neoplasm of the inferior gastric pole].

PMID- 7511950
TI  - Biodistributions of radioactive bipositive metal ions in tumor-bearing animals.
AB  - Distributions of the nuclides 65ZnCl2, 85SrCl2, 58CoCl2 and 103PdCl2 in tumor
      bearing animals were determined, and, in addition, the distributions of these
      nuclides in tumor tissues were observed. Their subcellular distribution in tumor
      and liver was also examined. Generally speaking, retention values of these
      bipositive metal ions in tumor were smaller than those of tri-, quadri- and
      pentavalent metal ions. In the case of 85SrCl2, a large amount of this nuclide
      was taken up by the bone and remained there for a long time. In the case of
      103PdCl2, 103Pd was avidly taken up by the kidney and liver. Very little of the
      103Pd taken up into the kidney and liver was excreted. 65Zn and 103Pd were
      concentrated in the viable tumor tissue and were not seen in necrotic tumor
      tissue. In the case of 58Co, lysosome played an important role in liver
      accumulation and played a minor role in tumor accumulation. The distribution of
      58Co in tumor and liver was fairly similar to that of 67Ga, 111In, 169Yb, 46Sc,
      51Cr, 95Zr, 181Hf, 95Nb and 182Ta which were reported previously. Lysosome did
      not play an important role in the accumulation of 65Zn, 85Sr and 103Pd into tumor
      and liver.

PMID- 7511952
TI  - [Gallbladder cancer: the clinical and therapeutic considerations].

PMID- 7511953
TI  - Amplification of the c-myc gene in human hepatocellular carcinoma: biologic
      significance.
AB  - To elucidate the prevalence and biologic significance of the c-myc gene in human
      hepatocellular carcinoma (HCC), DNA samples were taken from the paired tumorous
      and nontumorous tissues of 77 cases of resected primary HCC and were analyzed by
      Southern blot hybridization. We demonstrated modest, but significant c-myc
      amplification (group A) in 28 (36.4%) of the cases: 1.6- to 2.0-fold in 18, 2.1-
      to 3.0-fold in four, and > 3.0-fold in six. Compared to HCC without c-myc
      amplification (group B), group A HCC occurred more often in patients < 50 years
      old (54.5% vs 29.1%, p < 0.02) with serum alpha-fetoprotein (AFP) levels > 320
      ng/mL (61.1% vs 14.6%, p < 0.00002). Group A HCC occurred more frequently in
      patients with hepatitis B virus infection than in those with hepatitis C virus
      infection (p < 0.03). Group A HCC was more likely to be poorly differentiated
      (44.8% vs 10.5%, p < 0.004) and associated with intrahepatic portal vein spread
      (57.1% vs 28.6%, p < 0.02). The c-myc amplification did not correlate with sex or
      tumor size. For small HCC, group A had a worse one-year survival rate than group
      B (72.2% vs 90.9%, p < 0.04). These findings suggest that c-myc amplification is
      not an uncommon event in human hepatocarcinogenesis, occurs more frequently in
      young patients who have an elevated serum AFP level or HBV infection, and is
      related to the biologic behavior of HCC.

PMID- 7511954
TI  - Characterization of a human keratinocyte cell line immortalized by human
      papillomavirus 16 DNA.
AB  - A human keratinocyte cell line was established by transfecting neonatal foreskin
      keratinocytes of a Chinese with human papillomavirus (HPV) 16 DNA. As evidenced
      by the prolonged life span, the clone formation from a single cell, the piling up
      after prolonged culturing without passage and the chromosomal aneuploidy, this
      cell line possesses the biological characteristics of immortalization. The reason
      for obligatory growth requirements on epidermal growth factor (EGF) is not clear.
      The partial growth requirement on hydrocortisone for this immortalized cell line
      suggests that the glucocorticoid responding element of HPV 16 may play a role in
      cell immortalization. The constant over-expression of keratin 19 in this and
      other HPV 16 immortalized squamous epithelia indicates that it may serve as a
      useful marker for the potential malignant transformation of squamous epithelial
      cells. This immortalized cell line provides a model for investigating the factors
      and cofactors involved in carcinogenesis and differentiation of human epithelial
      cells.

PMID- 7511955
TI  - Access to specialist palliative care. May be expanding to quickly.

PMID- 7511956
TI  - Access to specialist palliative care. Purchasers come between complementary
      specialties.

PMID- 7511957
TI  - New techniques in assisted contraception. Parents and their children happy with
      assisted conception.

PMID- 7511958
TI  - A microplate assay for sialidase activity using plant lectin binding to N
      acetyllactosamine.
AB  - This paper presents a sensitive assay for sialidase activity based on the
      specific binding of lecting to N-acetyllactosamine. The substrate used for
      sialidase assay is fetuin (30-100 ng/50 microliters) with sialylated
      oligosaccharides, which was then coated on a 96-well microtiterplate. After
      removing sialic acids from the terminal positions of the glycoconjugate glycans
      by sialidase, it was subjected to biotin-labeled lectin (Ricinus communis
      agglutinin 120), which binds specifically to N-acetyllactosamine. This was
      followed by the addition of a peroxidase conjugated avidin-biotin complex. The
      amount of bound peroxidase was determined by a colorimetric assay. The
      sensitivity was enhanced 1000- to 10,000-fold compared to the colorimetric assay
      using a synthetic substrate such as 2-O-(p-nitrophenyl)-N-acetyl-alpha-D
      neuraminic acid (PNPN). In the established method, only very small amounts of
      substrate and sialidase were required; therefore, it can be applied to the
      quantitative assay of some sialidases from Vibrio cholerae, streptococcus, the
      influenza virus and rat liver.

PMID- 7511959
TI  - Potentiation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
      selective glutamate receptor function by a nootropic drug, idebenone.
AB  - Effect of idebenone on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid (AMPA)-selective glutamate receptor was evaluated using Xenopus oocytes
      injected with RNAs encoding mouse alpha 1 and alpha 2 AMPA receptors.
      Concanavalin A augmented current responses of the RNA-injected oocytes to
      glutamate, kainate, and AMPA and these responses were further potentiated by 100
      microM idebenone. The minimum concentration of idebenone that gave a significant
      potentiation was 10 microM for glutamate. These results suggest that idebenone
      acts on AMPA-selective glutamate receptor channels composed of alpha 1 and alpha
      2 subunits.

PMID- 7511960
TI  - Prostacyclin (PGI) receptor binding and cyclic AMP synthesis activities of PGI1
      analogues, SM-10906 and its methyl ester, SM-10902, in mastocytoma P-815 cells.
AB  - The prostacyclin I1 (PGI1) analogue, SM-10906 and its methyl ester, SM-10902,
      have been compared with the PGI2 analogue, iloprost, with respect to binding to
      the PGI2 receptor, stimulation of adenylate cyclase activity and inhibition of
      thrombin-induced Ca2+ mobilization in mastocytoma P-815 cells. SM-10906 displaced
      [3H]iloprost binding to the membrane fraction, the IC50 value being 100 nM, but
      showed very low affinity for the prostaglandin E (PGE) receptor. SM-10906 dose
      dependently stimulated GTP-dependent adenylate cyclase activity in the membrane
      fraction, the EC50 value being 35 nM. Furthermore, SM-10906 prevented a thrombin
      induced increase in the intracellular Ca2+ concentration, the IC50 value being
      300 nM. These IC50 and EC50 values are much lower than those of SM-10902. These
      results demonstrate that SM-10906, a stable PGI1 derivative, is an agonist for
      the [3H]iloprost-binding (PGI2) receptor, and that it prevents thrombin-induced
      Ca2+ mobilization through stimulation of the adenylate cyclase system in
      mastocytoma cells. On the other hand, a methyl ester derivative of PGI1, SM
      10902, was inactive in the binding assay, but it seems to be a partial agonist
      for adenylate cyclase activity [corrected].

PMID- 7511962
TI  - Anti-allergy actions of alkylphenyl alpha-D-mannopyranosides.
AB  - The inhibitory effects of alkylphenyl alpha-D-mannopyranosides on histamine
      release from rat peritoneal mast cells induced by an antigen-antibody reaction
      were examined. Among the compounds tested, 2,4,6-trimethylphenyl alpha-D
      mannopyranoside exhibited the strongest inhibitory effect. Furthermore, the 2,4,6
      trimethylphenyl alpha-D-mannopyranoside suppressed the Schultz-Dale reaction and
      48 h homologous passive cutaneous anaphylaxis (PCA), suggesting that this
      compound may be a useful lead compound in the development of novel anti-allergy
      drugs.

PMID- 7511961
TI  - Influences of alkylphenyl alpha-D-mannopyranosides on histamine release from rat
      peritoneal mast cells induced by concanavalin A.
AB  - The influence of mannose, glucose, galactose and their corresponding methyl and
      phenyl glycopyranosides, as well as a series of alkylphenyl alpha-D
      mannopyranosides, on histamine release from rat peritoneal mast cells induced by
      concanavalin A was examined. Among the compounds tested, the inhibitory effects
      of compounds bearing a 2,6-dimethyl substituent were stronger than the others.
      The results suggest that the binding ability of phenyl alpha-D-mannopyranoside
      may be markedly enhanced by the introduction of a 2,6-dimethyl substituent into
      the benzene nuclei of aglycones.

PMID- 7511963
TI  - Legionnaires' disease associated with hospitals.

PMID- 7511964
TI  - New code of practice for the control of legionellas in health care premises.

PMID- 7511965
TI  - [The cause-effect relationships between different indices of radiation lesions of
      the thymocytes].
AB  - The dependence of the kinetics of different thymocyte injuries of the
      experimental conditions was investigated. It was shown that the rate of cell
      death detecting by cell staining decreases with the increase of the dye molecular
      size. Different organic substances decrease the staining rate of the dead cells
      with trypan blue but increase the rate of DNA fragmentation. They change the
      kinetics of cell injuries development only after but not during irradiation.
      Development of pycnoses forestalls the DNA fragmentation. Basing on these
      findings the conclusion was made that the time-course of different thymocyte
      injuries development cannot be used for a statement what type of injuries--of
      plasmic membrane or cell nucleus--is initial.

PMID- 7511966
TI  - Effects of biliary endoprostheses on the extrahepatic bile ducts in relation to
      subsequent operation of the biliary tract.
AB  - Despite the widespread use of transpapillary biliary endoprostheses, little is
      known about their effect on the extrahepatic bile ducts. In an experimental study
      in dogs, we induced inflammatory changes in the bile ducts by stent insertion and
      studied the reversibility of these changes after stent removal. In addition, the
      consequences of a period of preoperative stenting for subsequent operation of the
      biliary tract and the eventual detrimental effects of stenting on the histologic
      factors of the liver were studied. Twenty-six mongrel dogs were randomly divided
      into four groups: group 1, stenting during four weeks; group 2, after four weeks
      stenting, construction of a hepaticojejunostomy; group 3, four days of common
      bile duct (CBD) ligation, four weeks stenting and hepaticojejunostomy, and group
      4, four days of CBD ligation and hepaticojejunostomy. All dogs were sacrificed
      two months after the last procedure. Hepatic biopsies were obtained during each
      procedure and bile duct biopsies during hepaticojejunostomy and upon sacrifice.
      Four weeks of stenting of a normal or obstructed CBD resulted in fibrosed bile
      ducts, showing severe chronic inflammation with papillary hyperplasia of the
      epithelium. All bile cultures grew fecal bacteria. Two months after stent
      removal, inflammation was still present, albeit less severe. Stenting and
      subsequent surgical treatment resulted in a higher incidence of postoperative
      complications (54 percent) compared with the control group (14 percent), although
      this did not reach statistical significance. Hepatic histologic factors were not
      markedly changed after transpapillary endoprosthesis placement, but after
      hepaticojejunostomy cholangiolitis was observed. Whenever transpapillary biliary
      endoprostheses are used, the local effects on the extrahepatic bile ducts and the
      subsequent bacterial contamination of the bile should be considered.

PMID- 7511967
TI  - Comparison of resectable and unresectable periampullary carcinomas.
AB  - Two hundred and fifty-eight patients with pathologically proved periampullary
      carcinomas who underwent surgical treatment between the years 1965 and 1992 were
      evaluated. Comparison was carried out between the resectable and unresectable
      groups. Carcinoma of the pancreatic head occurred in less than one-half (47
      percent) of the patients, and only 23 percent were resectable. In contrast,
      carcinoma of the ampulla of Vater had a similar rate of occurrence, but a much
      higher resectable rate (86 percent). Thus, carcinoma of the pancreatic head was
      the minor group (19 percent) in the resectable patients we studied. The main
      clinical presentations and durations of symptoms before diagnosis did not differ
      in the resectable and unresectable groups, so it was impossible to predict the
      resectability by symptoms. Incidences of diabetes mellitus and diarrhea increased
      twofold in the unresectable group. Preoperative biopsy was difficult to perform
      for those with carcinoma of the pancreatic head. Comparing pancreatoduodenectomy
      and palliative operation, pancreatoduodenectomy resulted in a higher complication
      rate (43 versus 13 percent), a higher surgical mortality rate (17 versus 9
      percent) and a longer hospitalization period (31 versus 20 days), but there was
      no statistical difference in the median survival time between the resectable and
      unresectable carcinomas of the pancreatic head (seven and one-half versus five
      months). Most of the patients (81 percent in the resectable group and 70 percent
      in the unresectable group) we studied died of cachexia with tumor recurrence.
      Although the advantage of pancreatoduodenectomy for resectable carcinoma of the
      pancreatic head was questioned, we still recommend this procedure for all
      periampullary carcinomas to avoid depriving the occasional patients with
      pancreatic carcinomas of long term survival and forfeiting the chance of cure for
      some misdiagnosed patients with other more favorable periampullary carcinomas.

PMID- 7511968
TI  - Ion channels: structure and function.
AB  - Ion channels are ubiquitous membrane proteins in mammalian cells. Their critical
      physiological roles include control of the electrical potential across the
      membrane, facilitation of neuromuscular and neuronal transmission, signal
      transduction, and regulation of secretion and contractility. The alliance of
      techniques in biochemistry, electrophysiology, pharmacology, and molecular
      biology has provided insights into the three-dimensional structure of channel
      proteins and has allowed specific aspects of functional correlates to be better
      understood. Promises for the future include molecular genetic approaches to the
      treatment of disorders such as long QT syndrome and more rational design of drugs
      targeted to ion channels, including antiarrhythmic agents.

PMID- 7511970
TI  - Transurethral grooving of the prostate in the treatment of patients with benign
      prostatic hyperplasia. An alternative to transurethral incision.
AB  - Various alternatives exist for the treatment of bladder outlet obstruction due to
      benign prostatic hyperplasia (BPH). Incision of the bladder neck and prostate has
      proved its efficacy in many studies, especially in small prostates. The major
      drawback of the procedure is inability to obtain tissue specimens to exclude
      malignancy. We introduced a method to overcome this drawback by incising grooves
      at 5 and 7 o'clock with standard resection loops which created not only the
      incisions but also provided enough tissue for pathological examination. Twenty
      five patients with BPH underwent transurethral grooving. Pre- and post-operative
      urodynamic studies revealed significant improvement in both maximum and average
      flow rates. The re-operation rate in the entire group was 12%. Transitional cell
      carcinoma of the prostatic urethra was detected in 1 patient, which proved its
      superiority to standard incision procedures.

PMID- 7511969
TI  - Quantitative analysis of adrenergic alpha-1 and alpha-2 receptors in human
      prostatic urethral tissue.
AB  - We measured the adrenergic alpha-1 and alpha-2 receptors in 3 types of prostatic
      tissue (prostatic urethral mucosa, prostatic adenoma and prostatic capsule) in a
      group of patients with benign prostatic hypertrophy (BPH) and in another group
      without BPH, using radioligand binding techniques. In all tissues examined, more
      alpha-1 and alpha-2 receptors were found in the hypertrophy group than in the
      other group. The increase in density of these receptors in the hypertrophy group
      was most marked in the prostatic adenoma. The density of alpha-1 and alpha-2
      receptors was almost the same in the adenoma in both groups. The prostatic
      capsule and urethra in both groups contained more alpha-1 than alpha-2 receptors.
      Both receptors were found more in the adenoma than in the other 2 tissues in both
      groups. These results suggest that alpha-1 and alpha-2 receptors both play an
      important part in the symptoms of benign prostatic hypertrophy.

PMID- 7511971
TI  - Prostate specific antigen in screening for recurrence following radical
      prostatectomy for localised prostatic cancer.
AB  - Eighty-five patients treated by radical prostatectomy for clinically localised
      prostatic cancer were followed up for 1 to 4 years with measurement of prostate
      specific antigen (PSA). Six patients with recurrences had elevated levels (cut
      off level was 1.0 ng/ml). PSA is therefore considered an excellent tool for
      monitoring treatment failures. Levels exceeding 1.0 ng/ml preceded evidence of
      tumour recurrence by a mean interval of 11 months. PSA offers the possibility of
      detecting residual prostatic cancer after surgery. It is not known, however,
      whether these patients would have benefited from adjuvant endocrine or early
      radiotherapy.

PMID- 7511973
TI  - Children with alcohol misusing parents.
AB  - Children of alcohol abusing parents (COAs) now receive more attention in their
      own right but data from methodologically sound studies is still thin. Genetic
      vulnerability increases risk of comorbidity for other psychiatric disorders and
      cognitive deficits as well as substance abuse. Neuropsychological effects of
      maternal alcohol consumption in pregnancy are more common than previously thought
      and paternal alcohol abuse may contribute to fetal damage. Family functioning is
      severely affected and COAs are at risk for child abuse though the strength of the
      association needs clarifying. Family drinking patterns are associated with
      teenage alcohol abuse and early induction increases the risk of addiction. COAs
      have raised morbidity rates for emotional and behavioural disturbance with impact
      on the developing child and separate prognostic significance for future adult
      morbidity other than alcoholism. Ethical considerations arise about the welfare
      of children cared for by alcohol abusing parents.

PMID- 7511972
TI  - Evaluation of Ki-67 monoclonal antibody as prognostic indicator for prostatic
      carcinoma.
AB  - Prostate tissue containing either primary adenocarcinoma (45 patients) or benign
      hyperplasia (15 patients) was immunostained with the monoclonal antibody Ki-67,
      which recognises a human nuclear antigen expressed by human cycling cells. The
      percentage of cells staining positive was considered a measure of proliferation.
      This derived Ki-67 index was higher for carcinomas than for hyperplastic glands.
      Within the group of carcinomas, Ki-67 indices in patients with metastatic disease
      were significantly higher than in those without and there was a trend towards
      increasing Ki-67 indices with increasing Gleason grade. When patients with
      prostate cancer were prospectively followed up, the Ki-67 index did not predict
      either disease progression or hormone responsiveness. Ki-67 immunostaining may
      define a group of patients with prostate cancer of poor prognosis.

PMID- 7511975
TI  - Channel shutdown: a response of hippocampal neurons to adverse environments.
AB  - Stretch-activated ion channels have been discovered in the membrane of many types
      of cells, but their presence in neurons is uncertain. We used freshly dissociated
      rat hippocampal neurons to study the effect of hypotonic swelling but,
      surprisingly, the isolated neurons did not swell. Voltage-dependent whole-cell
      membrane currents mediated by K+, Na+ and Ca2+ were rapidly and reversibly
      suppressed during sudden exposure to strongly hypo-osmotic, hyper-osmotic or
      glucose deficient solutions. The amplitudes of the sustained components of K+ and
      Ca2+ currents were more depressed than transient currents, but the rate of decay
      of transient K+ current greatly accelerated. The voltage dependence of activation
      and of steady state inactivation of residual K+ and Ca2+ currents were not
      shifted. The current holding membrane potential at -70 mV and therefore the
      conductance at that voltage were unchanged or somewhat decreased. Capacitive
      (charging) membrane current was not affected. Changes in tail current suggested
      moderate loss of cytosolic K+ in some but not in all cells. We conclude that
      channel shutdown is a uniform response of neuron somata and proximal dendrites to
      various adverse environments. Hypothetically we propose that swelling was
      prevented in anisosmotic conditions because membrane water permeability
      decreased.

PMID- 7511974
TI  - Human astrocytes are only partially competent antigen presenting cells. Possible
      implications for lesion development in multiple sclerosis.
AB  - Highly purified astrocyte cultures from human embryonic brain were examined for
      their capacity to present antigen to human leukocyte antigen (HLA) class II
      compatible, cytolytic CD4+ T lymphocytes. Most astrocytes constitutively
      expressed HLA class I products and LFA-3 (CD58). Constitutive expression of HLA
      class II, LFA-1 alpha (CD11a) and ICAM-1 (CD54) was lower and varied among
      different cultures, while LFA-2 (CD2) was absent. IFN-gamma alone or in
      combination with TNF-alpha strongly enhanced expression of HLA class I, HLA-DR, 
      DP, -DQ, LFA-1 alpha and ICAM-1, but did not affect expression of LFA-2 (CD2) and
      LFA-3 (CD58). TNF-alpha alone induced only HLA class I and ICAM-1, but not HLA
      class II or LFA-1 alpha. Cytokine treated, but not untreated astrocytes were able
      to present protein (auto-)antigens to specific T lymphocyte lines. Astrocytes
      expressing appropriate major histocompatibility complex class II products were
      lysed by CD4+ T cells specific for myelin basic protein or tetanus toxoid. The
      lytic response was antigen dose dependent and HLA-DR restricted. It could be
      blocked by antibodies against HLA-DR determinants and against the adhesion
      molecules LFA-1 alpha and ICAM-1. In remarkable contrast to their susceptibility
      to T cell lysis, antigen presenting astrocytes were not only completely unable to
      induce T cell proliferation but even inhibited proliferation. The results
      indicate that, although human astrocytes have the potential to present protein
      antigens to CD4+ T cells, they do not induce the co-stimulatory factors required
      to trigger the complete T cell activation programme.

PMID- 7511976
TI  - Effects of ageing on tachykinin function in the basal ganglia.
AB  - The effects of ageing on tachykinin-induced behaviours and tachykinin receptors
      were investigated in the rat. Infusion of the NK-3 tachykinin agonist senktide
      (0.25, 0.5 and 1 nmol) into the substantia nigra induced locomotion in young (4-6
      months) animals but this response was attenuated in middle-aged (12 months) and
      old (27 months) animals. In contrast, senktide-induced wet dog shakes were not
      significantly affected by age. In the ventral tegmental area, senktide induced
      locomotion and wet dog shakes with bell-shaped dose-response curves which were
      unaffected by age. Senktide suppressed grooming but the effect reached
      significance in the older animals only. Quantitative receptor autoradiography
      revealed no effect of age on NK-1 tachykinin receptor density in the striatum
      while NK-3 receptor density declined in the ventrolateral striatum and to a
      nonsignificant degree in the substantia nigra but not in other striatal
      subregions or the ventral tegmental area. We conclude that ageing of the nervous
      system is not associated with widespread changes in tachykinin binding but
      differences in behavioural response to tachykinin agonists may reflect changes in
      other transmitter systems which respond to tachykinin input.

PMID- 7511977
TI  - Morphological diversities of CD44 positive astrocytes in the cerebral cortex of
      normal subjects and patients with Alzheimer's disease.
AB  - The localization of CD44 was investigated immunohistochemically in postmortem
      human brain tissue of control subjects and patients with Alzheimer's disease.
      CD44 is a multifunctional cell surface glycoprotein that serves as a receptor for
      hyaluronic acid, collagen types I and VI, and mucosal vascular addressin. In gray
      matter, it was found to be associated with some astrocytes of both protoplasmic
      and fibrous morphology. These positively stained astrocytes were most frequently
      observed in association with blood vessels, and had morphologies that were highly
      comparable to those described with the Golgi technique. Double immunostaining for
      CD44 and glial fibrillary acidic protein (GFAP) revealed that a significant
      number of these astrocytes were positive for both antigens. However, GFAP
      staining was mostly confined to the cell somata and proximal processes, while
      CD44 staining extended to a rich and extensive array of processes. Occasional
      CD44 positive cells of spherical morphology with a few thin varicose processes
      were observed. Their processes formed thick terminations on blood vessels,
      suggesting that these cells are a special class of astrocyte. In Alzheimer's
      disease brain, the number of CD44 positive astrocytes increased dramatically.
      These data suggest that astrocytes have very extensive branching patterns, which
      are reflected by CD44 staining patterns. CD44 may be an important adhesion
      molecule for these astrocytic processes.

PMID- 7511978
TI  - The peripheral and central projections of the Edinger-Westphal nucleus in the
      rat. A light and electron microscopic tracing study.
AB  - The peripheral and central efferent projections of the rostral part of the
      Edinger-Westphal nucleus in the rat were investigated at the light and electron
      microscopic level by means of iontophoretic injections of the anterograde tracer
      Phaseolus vulgaris-leucoagglutinin and retrograde tracer injections of Fast blue
      and Nuclear yellow into the facial nucleus and into the principal olive. Two
      pathways leaving the rostral part of the Edinger-Westphal nucleus were studied, a
      peripheral and a central descending pathway. Fluorescent experiments demonstrated
      that the central pathway fibers originated from distinct individual Edinger
      Westphal neurons. These neurons were mainly distributed throughout the rostral
      part of the Edinger-Westphal nucleus and had fusiform cell bodies. The neurons
      rarely form collateral projections. The central descending pathway left the
      Edinger-Westphal nucleus medially and terminated bilaterally in the principal
      olive, in the subnuclei A, B and C of the inferior olive and ipsilaterally in the
      medial accessory olive. The central pathway also terminated contralaterally in
      the lateral parabrachial nucleus, the facial nucleus, the trigeminal brainstem
      nuclear complex, the lateral reticular nucleus and the rostroventral reticular
      nucleus. The projection to the facial nucleus provides evidence for the existence
      of a polysynaptic loop forming the central part of the corneal blink reflex.
      Projections from the Edinger-Westphal nucleus to the cerebellar cortex or the
      deep nuclei, as described in cat and primate, could not be confirmed. The
      peripheral pathway left the Edinger-Westphal nucleus ventrally and terminated on
      dendrites of ciliary ganglion cells, along smooth muscle cells of ciliary
      ganglion associated arterioles and in the proximity of ciliary ganglion
      associated venules. The central and peripheral terminals that originate in the
      Edinger-Westphal nucleus all had similar ultrastructural features: clear, round
      vesicles and electron dense mitochondria. The terminals originating from the
      central descending pathway were often found to be arranged in glomerular-like
      structures. The central and peripheral terminals made asymmetric synaptic
      membrane specializations (Gray type one), except terminals innervating the
      ciliary ganglion associated vessels, which showed no synaptic contacts.

PMID- 7511979
TI  - The subdivisions of the intermediolateral nucleus in the sacral spinal cord of
      the cat.
AB  - The subdivisions of the sacral intermediolateral nucleus (IML) of the cat have
      been studied by using a double-labeling technique of retrograde Fluoro-gold (FG)
      and wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) tracing.
      The parasympathetic preganglionic neurons (PGNs) that were labeled by the FG
      injected into the pelvic nerve formed a 'V'-shaped column known as the sacral
      parasympathetic nucleus (SPN) in the sacral IML. The neurons that were labeled by
      the WGA-HRP applied to the lateral parabrachial nucleus (PBL) formed an elongated
      spindle-shaped column extending throughout the IML of the sacral segments. We
      designated it by the name of sacral visceral sensory nucleus (SVSN). These
      findings indicate that the sacral IML of the cat contain two distinct
      subdivisions, SPN and SVSN.

PMID- 7511980
TI  - Deficits in working memory following inhibition of hippocampal nitric oxide
      synthesis in the rat.
AB  - In order to elucidate the roles of hippocampal nitric oxide (NO) synthesis in
      working and reference memory performance of rats, the effects of intrahippocampal
      injections of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L
      NAME), on this behavior were examined with a three-panel runway task. In the
      working memory task, L-NAME, injected bilaterally at 10 and 32 micrograms/side
      into the dorsal hippocampus, significantly increased the number of errors
      (attempts to pass through two incorrect panels of the three panel-gates at four
      choice points). This effect of intrahippocampal L-NAME (32 micrograms/side) on
      working memory was attenuated by concurrent injection of 100 micrograms/side L
      arginine, the precursor of NO. Intrahippocampal injection of the inactive isomer
      D-NAME at doses up to 32 micrograms/side had no effect on the number of working
      memory errors. In the reference memory task, neither L-NAME nor D-NAME affected
      the number of errors when injected into the hippocampus at doses up to 32
      micrograms/side. These results suggest that processes mediated by NO synthesis in
      the hippocampus are involved in working memory, but not in reference memory.

PMID- 7511981
TI  - Innervation of normal human sural and optic nerves by noradrenaline- and peptide
      containing nervi vasorum and nervorum: effect of diabetes and alcoholism.
AB  - Histochemical, immunohistochemical and neurochemical techniques were used to
      examine the innervation of epineurial nerve sheaths and fascicular nerve bundles
      of human sural and optic nerves from controls and patients with peripheral
      neuropathy due to diabetes or alcoholism. The normal distribution of autonomic
      nerves in both nerve trunk sheaths consisted of a dense innervation by
      noradrenaline (NA)-containing nerves of the vasa nervorum, together with some
      fibres in the nervi nervorum. Intrafascicular NA-containing nerves were only
      present in the sural nerve. Vasoactive intestinal polypeptide (VIP)- and
      neuropeptide Y (NPY)-containing nerves also innervated the vasa nervorum and
      nervi nervorum of the nerve sheaths, although their density was considerably
      less. Substance P (SP)-containing nerves were sparse and primarily
      intrafascicular. Neurochemical assays for NA, VIP, NPY and SP in fascicular and
      epineurial preparations from the sural and optic nerves confirmed the light
      microscopical observations. Post mortem delay significantly affected the NA
      levels in the sural nerve but not in the optic nerve while the NA
      fascicular/epineurial ratio for the sural nerve was independent of this factor.
      Age, sex and the presence of alcohol at time of death had no effect on
      transmitter levels in normal sural nerves. In the optic nerve fascicles NA levels
      were higher in females than in males. In patients with peripheral neuropathy
      there was a significant reduction in the SP fascicular/epineurial ratio in both
      the optic nerve, which was histologically normal, and in the sural nerve, where
      there was evidence of neuropathy. The NA fascicular/epineurial ratio was also
      significantly reduced in the sural nerve from patients with peripheral neuropathy
      with a possible greater effect in diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511982
TI  - Effects of tachykinins on phosphoinositide metabolism in the hypothalamus: is the
      NK1 receptor involved?
AB  - Substance P (SP) has been shown to stimulate the hydrolysis of inositol
      phospholipids in peripheral tissues and in the brain. In mammalian peripheral
      tissues, three tachykinin receptor subclasses, neurokinin 1 (NK1), neurokinin 2
      (NK2) and neurokinin 3 (NK3), have been identified. The purpose of our study was
      to pharmacologically characterize the SP receptors in the hypothalamus using
      phosphoinositide breakdown as a functional response. SP, previously described as
      a NK1 agonist, and Neurokinin A (NKA), previously described as a NK2 agonist,
      stimulated phosphoinositide breakdown in the hypothalamus in a dose-dependent
      fashion, with SP being more potent than NKA. The NK2-selective antagonist L
      659,877, at a dose of 10(-6) M, abolished the effect of SP (10(-8) M) without
      affecting basal phosphoinositide breakdown. However, this NK2-selective
      antagonist did not inhibit the NKA-induced stimulation in phosphoinositide
      metabolism. The NK1-selective antagonist L-668,169 stimulated phosphoinositide
      metabolism at a concentration of 10(-6) M, but not at 10(-8) M. This NK1-receptor
      antagonist did not significantly inhibit the effect of SP on phosphoinositide
      metabolism. Spantide II, another NK1-selective antagonist, also stimulated
      phosphoinositide metabolism at a dose of 10(-6) M. Like L-668,169, spantide II
      failed to inhibit the SP-induced stimulation of phosphoinositide metabolism, and
      even potentiated the response to SP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7511983
TI  - Effect of Calphostin C (PKC inhibitor) on daunorubicin resistance in P388/ADR and
      HL60/AR cells: reversal of drug resistance possibly via P-glycoprotein.
AB  - Calphostin C is a potent and specific inhibitor of protein kinase C (PKC). In
      this investigation we examined the effect of Calphostin C (without prior exposure
      to light) on daunorubicin (DNR) accumulation and sensitivity to DNR in multidrug
      resistant (MDR) murine leukemia P388/ADR and human myeloid leukemia HL60/AR
      cells. P388/ADR cells overexpress P-glycoprotein, whereas HL60/AR cells lack any
      expression of P-glycoprotein (both at mRNA and protein levels). Calphostin C, in
      a concentration-dependent manner, increased the accumulation of DNR in P388/ADR
      cells and partially reversed (threefold) the DNR resistance in P388/ADR cells but
      had no effect on either of the parameters in HL60/AR cells. Calphostin C-induced
      increased accumulation of DNR in P388/ADR cells was due to increased uptake and
      decreased efflux of DNR. Furthermore, Calphostin C increased the uptake and
      decreased the efflux of rhodamine 123 (a substrate for P-gp) in P388/ADR cells
      but had no such effect in P388 cells. In addition, Calphostin C without exposure
      to light did not inhibit PKC activity in any of the cell lines studied. Taken
      together, these data suggest that Calphostin C may reverse drug resistance via P
      glycoprotein independently of its effect on PKC activity. Therefore, any data
      regarding the effect of Calphostin C on the reversal of MDR should be interpreted
      in the light of these findings.

PMID- 7511984
TI  - Sequence analysis of the proximal promoter region of the human alpha-fetoprotein
      gene in hepatocellular carcinoma.
AB  - We have examined whether or not mutations exist in the proximal promoter region
      of the human alpha-fetoprotein (AFP) gene in the hepatocellular carcinoma (HCC)
      tissue. Genomic DNA was extracted from four patients: one HCC tissue, one HCC and
      its corresponding non-cancerous (cirrhosis) tissues, one liver cirrhosis (LC)
      tissue without HCC and one matching HCC tissue and peripheral blood leukocytes.
      Serum concentrations of AFP in the patients ranged from less than 5 to 10,138
      ng/ml. Nucleotide sequence was determined by direct sequencing using a single
      stranded DNA template that was produced first through the polymerase chain
      reaction (PCR) amplification and then asymmetric PCR. In one HCC tissue taken
      from the patient with a high concentration of serum AFP, nucleotides different
      from published ones were detected at -120 and -113. These changes, however,
      probably reflect a DNA polymorphism, because peripheral blood leukocytes of the
      same patient had the same changes. Including this patient, no mutations in the
      region from -160 to -10 were detected in the HCC specimens we have examined.
      These results suggest that the extremely proximal promoter region of the AFP gene
      where glucocorticoid-responsive element and HNF-1 binding sites exist is not
      responsible for the re-expression of AFP in HCC.

PMID- 7511985
TI  - Analysis by the reductive-cleavage method of a polysaccharide containing 2
      acetamido-2,6-dideoxy-D- and -L-galactopyranosyl residues.
AB  - Modifications of the reductive-cleavage method for the analysis of 2-acetamido
      sugars were tested using a polysaccharide containing alpha-linked 2-acetamido-2,6
      dideoxy-L-galactopyranosyl (Fuc pNAc) residues, beta-linked D-Fuc pNAc residues
      and 2-linked D-glucopyranosyl residues. Reductive cleavage of the fully
      methylated O-antigenic polysaccharide of Pseudomonas aeruginosa ATCC 33358 in the
      presence of triethylsilane and trimethylsilyl trifluoromethanesulfonate, followed
      by quenching with methanol and subsequent acetylation, unexpectedly resulted in
      nearly complete cleavage of all glycosidic linkages to yield 2-O-acetyl-1,5
      anhydro-3,4,6-tri-O-methyl-D-glucitol (1a) and methyl 3-O-acetyl-2,6-dideoxy-4-O
      methyl-2-(N-methylacetamido)-beta-D- and -L- galactopyranosides (3a and 4a) as
      the major products. When the reductive-cleavage reaction was quenched with (S)-2
      butanol, the major FucNAc derivatives were the diastereomeric (S)-2-butyl
      glycosides 15a and 17a, confirming the presence of enantiomeric FucNAc residues
      in the repeating unit of the polysaccharide. However, compounds 15a and 17a were
      not detected in equimolar proportions, presumably as a consequence of
      diastereoselectivity in the reaction of the chiral alcohol with the respective
      intermediate oxazolinium ions. Reductive cleavage of the fully methylated
      polysaccharide in the presence of a mixture of trimethylsilyl methanesulfonate
      and boron trifluoride etherate, followed by quenching with methanol, resulted in
      incomplete cleavage, giving rise to three disaccharide derivatives whose
      sequences overlap that of the trisaccharide repeating unit in the polysaccharide.
      The lack of selectivity for cleavage at beta-D-FucNAc residues suggests that the
      alpha-L-FucNAc residues underwent anomerization prior to transglycosidation.

PMID- 7511986
TI  - Synthesis of methyl O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-D-galactopyranosides
      specifically deoxygenated at position 3, 4, or 6 of the galactose residue.
AB  - The title disaccharides were synthesized by condensation of 2,3,4-tri-O-benzoyl
      alpha-L-rhamnopyranosyl bromide with suitably protected, deoxygenated derivatives
      of methyl alpha-D-galactopyranoside. Deoxygenation was achieved via activation of
      a protected methyl alpha-D-gluco- or galacto-pyranoside with N,N'
      thiocarbonyldiimidazole followed by treatment with tributyltin hydride and
      azobisisobutyronitrile. At position 3, the deoxygenation was more successful when
      performed with the tri-O-benzoylated precursor, rather than the tri-O-benzylated
      one. The corresponding nucleophile was obtained by benzylidenation of the methyl
      3-deoxy-alpha-D-xylo-hexopyranoside. The preparation of the glycosyl acceptor
      deoxygenated at position 4 could be pursued starting from derivatives having
      either the D-galacto or the D-gluco configuration. The pathway involving the
      former was found superior.

PMID- 7511987
TI  - The structure of a core oligosaccharide component from Hafnia alvei strain 32 and
      1192 lipopolysaccharides.

PMID- 7511988
TI  - QT prolongation and possibility of ventricular arrhythmias after intracoronary
      papaverine.
AB  - The incidence of ventricular arrhythmias following the intracoronary injection of
      papaverine was assessed. A 3F coronary Doppler catheter was placed in the
      proximal left anterior descending artery and 6-12 mg of papaverine was injected
      into the left coronary artery in 42 patients. After intracoronary papaverine, the
      corrected QT interval on the electrocardiogram was prolonged from 0.43 +/- 0.03
      to 0.49 +/- 0.07 s (p < 0.001). Occasional premature beats were observed in 2
      patients (4.5%) with dilated cardiomyopathy. In 1 patient (2.3%) with 99%
      stenosis of the left anterior descending artery, polymorphous ventricular
      tachycardia with marked QT prolongation occurred. This patient also had
      hypokalemia (2.5 mEq/l) due to primary aldosteronism. In conclusion, careful use
      of intracoronary papaverine is necessary because of the risk of occasional
      serious ventricular arrhythmias.

PMID- 7511989
TI  - Multiple effects of SK&F 96365 on ionic currents and intracellular calcium in
      human endothelial cells.
AB  - 1. Multiple effects of the imidazole compound SK&F 96365 have been evaluated on
      endothelial cells from human umbilical vein using a combined patch clamp and
      Ca(2+)-microfluorimetric technique (Fura-2). 2. At concentrations of 100 mumol/l
      or higher of SK&F 96365, the block of the receptor-mediated Ca2+ entry overlaps
      with the activation of another Ca(2+)-entry mechanism, which is associated with a
      non selective cationic current. 3. This rise in [Ca2+]i depends on the
      extracellular Ca(2+)-concentration, and the entry pathway is in contrast with the
      receptor-mediated Ca(2+)-entry pathway permeable to Ni2+, as shown by quenching
      of the Fura-2 fluorescence signal. 4. The concentration of SK&F 96365 for half
      maximal increase in [Ca2+]i was 141 +/- 19 mumol/l (n = 16). 5. SK&F 96365
      activated a current that reversed at +11.8 +/- 2.1 mV (n = 21) when measured
      using nystatin-perforated patches with either Cs+ or K+ in the pipette and 140
      Na+, 1.5 Ca2+ in the bath (chloride equilibrium potential ECl = -36 mV). 6. SK&F
      96365 (200 mumol/l) blocked an inwardly rectifying K+ current in endothelial
      cells independently of [Ca2+]i. This block caused depolarization of the
      endothelial cells from -55.3 +/- 2.57 mV (n = 33) to -10 +/- 5.5 mV (n = 6). This
      block was concentration-dependent, half maximal block occurred at a concentration
      of about 40 mumol/l SK&F 96365. 7. In cells which showed an outwardly rectifying
      current, this outward component was also completely blocked by 200 mumol/l SK&F
      96365. 8. It is concluded that SK&F 96365 reversibly activates a non-selective
      cation channel at concentrations higher than 100 mumol/l, but also blocks K+
      currents in endothelial cells independently of [Ca2+]i. These multiple effects
      overlap with the proposed block of receptor-mediated Ca2+ entry. The block of
      K(+)-channels may in unclamped cells reduce the driving force for Ca2+, and
      thereby interfere with the Ca(2+)-influx.

PMID- 7511990
TI  - The calcium release channel of sarcoplasmic reticulum is modulated by FK-506
      binding protein: effect of FKBP-12 on single channel activity of the skeletal
      muscle ryanodine receptor.
AB  - The calcium release channel/ryanodine receptor of rabbit skeletal muscle
      sarcoplasmic reticulum is tightly associated with the immunophilin FK-506 binding
      protein (FKBP-12). The immunosuppressant drug FK-506 effectively dissociates FKBP
      12 from the calcium release channel of terminal cisternae (TC) vesicles.
      Furthermore, calcium flux measurements of TC indicate that FKBP-12 stabilizes the
      closed conformation of the calcium release channel of TC [Timerman AP, Ogunbunmi
      E, Freund EA, Wiederrecht G, Marks AM, Fleischer S. (1993) J. Biol. Chem., 268,
      22992-22999]. In this report, the effect of FKBP on single channel recordings of
      the calcium release channel/ryanodine receptor of TC is measured directly. Single
      channel recordings of the ryanodine receptor were obtained by fusion of TC
      vesicles into planar bilayers. The channel devoid of FKBP, retains key diagnostic
      features. That is, activation by Ca2+ and ryanodine, inhibition by Mg2+ (mM) and
      ruthenium red (microM), and its unitary conductance remain the same. Recordings
      of the calcium release channel obtained from the FKBP-deficient TC vesicles, as
      compared with control TC, have greater open probability and longer mean open
      times in a free calcium concentration range of 70 nM to 1.2 microM. The
      sensitivity of the channel to caffeine is also enhanced by the removal of FKBP.
      The enhanced channel activation of FKBP-deficient TC is reversed by rebinding
      recombinant FKBP-12 in a cyclical fashion. We conclude that FKBP modifies the
      channel behavior of the calcium release channel of skeletal muscle sarcoplasmic
      reticulum.

PMID- 7511991
TI  - Effect of 5-azacytidine on expression of the human DNA repair enzyme O6
      methylguanine-DNA methyltransferase.
AB  - The role of methylation of CpG dinucleotides in the regulation of O6
      methylguanine-DNA methyltransferase (MGMT) gene expression has been investigated.
      A previous observation, that cell lines deficient in MGMT (Mer-) are methylated
      in a SmaI site in the MGMT gene promoter whereas MGMT-expressing cells (Mer+) are
      unmethylated in the same site, has been extended to a total of 30 cell lines,
      tumors and normal tissues. To examine further the association between methylation
      in the MGMT promoter and the Mer- phenotype we have treated Mer+ and Mer- cell
      lines with 5-azacytidine to inhibit DNA methylation. Reduced methylation in the
      SmaI site coincided with induction of MGMT expression for one of three Mer- cell
      lines. MGMT increased several-fold further upon continued culture of the induced
      cells in the absence of 5-azacytidine, coincident with an abrupt increase in
      methylation in the body of the MGMT gene even though the SmaI site remained
      demethylated. These results, and those of other previous studies, suggest that
      methylation of sequences within the MGMT gene promoter and methylation within the
      body of the gene have opposite effects.

PMID- 7511992
TI  - DNA adducts among personnel servicing and loading diesel vehicles.
AB  - The levels of aromatic DNA adducts were compared by the 32P-postlabeling assay
      between the lymphocytes isolated from bus maintenance and truck terminal workers,
      using hospital mechanics as a control group. The adduct levels were elevated in
      all the bus and truck terminal workers. Within the bus maintenance personnel,
      garage workers had the highest levels of adducts. Within the terminal workers
      those driving diesel forklifts had the highest adduct levels. The results suggest
      that diesel exhaust contributes to the level of adducts.

PMID- 7511993
TI  - Differential expression of the cell adhesion molecules ICAM-1, VCAM-1, and E
      selectin in normal and posttransplantation myocardium. Cell adhesion molecule
      expression in human cardiac allografts.
AB  - BACKGROUND: Cell adhesion molecules (CAMs) have been implicated in cardiac
      allograft rejection. However, previous studies have used qualitative analysis of
      immunohistochemical data and did not exclude patients with infection or
      malignancy. METHODS AND RESULTS: We analyzed 40 endomyocardial biopsy specimens
      from 25 cardiac transplant patients and 8 specimens from patients undergoing
      cardiac surgery. Patients with evidence of infection or malignancy were excluded.
      Specimens were stained with monoclonal antibodies against ICAM-1, E-selectin,
      VCAM-1, and PECAM-1 (which labels all vessels). ICAM-1 expression was assessed by
      counting ICAM-1-positive vessels and dividing by the total number of vessels
      (measured by PECAM staining). Specimens were scored as positive or negative for
      VCAM-1 and E-selectin. We also determined whether serum-soluble ICAM-1 levels
      (sICAM) correlated with rejection by evaluating 145 serum specimens from 48
      cardiac transplant patients and 8 specimens from patients undergoing diagnostic
      cardiac catheterization. ICAM-1 was present on 50% to 60% of vessels in normal
      and nonrejecting specimens. Specimens with histologically significant rejection
      (focal moderate, moderate, or severe) had an increased percentage of ICAM-1
      positive vessels: focal moderate, 77%; moderate/severe, 92% (P < .01). E-selectin
      expression did not differ between groups. VCAM-1 frequently was not present on
      rejecting specimens. No correlation was noted between sICAM levels and the
      presence or absence of rejection. CONCLUSIONS: (1) ICAM-1 expression is strongly
      correlated with histologically significant cardiac allograft rejection. (2) The
      use of PECAM-1 staining as a vascular marker permits quantitative analysis of
      ICAM-1 expression. (3) VCAM-1 and E-selectin are not consistently increased
      during cardiac allograft rejection. (4) sICAM levels do not accurately reflect
      endomyocardial biopsy results.

PMID- 7511994
TI  - High [Ca2+]o-induced electrical heterogeneity and extrasystolic activity in
      isolated canine ventricular epicardium. Phase 2 reentry.
AB  - BACKGROUND: Elevated intracellular calcium activity is thought to play an
      important role in arrhythmia induction, particularly during ischemia and
      reperfusion. Delayed after-depolarization-induced triggered activity and
      intracellular communication problems are thought to be responsible. METHODS AND
      RESULTS: Increased extracellular calcium levels and rapid pacing are
      interventions known to elevate intracellular calcium activity. The present study,
      conducted using standard microelectrode techniques, was designed to compare the
      effects of increased [Ca2+]o (1.8 to 5.4 mmol/L) in isolated canine ventricular
      epicardial and endocardial tissues and to test the hypothesis that elevated
      intracellular calcium activity contributes to arrhythmogenesis in working
      ventricular myocardial tissues by promoting electrical heterogeneity. High
      [Ca2+]o caused a slight abbreviation of action potential duration (APD90) in
      endocardium but more dramatic rate-dependent and dynamic changes in epicardium.
      Under steady-state conditions, epicardium displayed a marked abbreviation of
      APD90 at fast rates but no significant changes at slow rates. A significant
      augmentation of phase 1 was evident at the faster stimulation rates. Vmax and
      conduction velocity were only slightly reduced. The marked abbreviation of the
      epicardial response at the factor rates was due to loss of the action potential
      dome. Recovery of the dome after deceleration was not synchronous throughout the
      preparation. As a consequence, a sudden slowing of rate caused marked dispersion
      of repolarization among neighboring epicardial sites, giving rise to ectopic
      activity via a phase 2 reentry mechanism. These effects of high [Ca2+]o were
      mimicked by exposure of the preparations to low [Na+]o. Electrical homogeneity
      was restored and arrhythmias were abolished after addition of the Ito blocker 4
      aminopyridine 1 mmol/L. 4-Aminopyridine also eliminated the differential response
      of epicardium and endocardium to high [Ca2+]o. CONCLUSIONS: Our data demonstrate
      the induction of marked electrical heterogeneity and reentrant activity by high
      [Ca2+]o and rapid stimulation, conditions known to elevate [Ca2+]i. The results
      suggest that increased intracellular calcium activity, as occurs during ischemia
      and reperfusion, may contribute to the development of electrical inhomogeneity in
      the ventricle and thus to the genesis of ventricular arrhythmias through a
      mechanism other than triggered activity, namely, phase 2 reentry. Our data point
      to an increase in net outward current as the underlying mechanism for the calcium
      induced changes. Our results also suggest that the presence of a prominent
      transient outward current (Ito) in epicardium sensitizes that tissue to the
      effects of high calcium. Finally, the results suggest that Ito blockers can
      reverse high calcium-induced electrical heterogeneity and thus can exert
      antiarrhythmic actions.

PMID- 7511995
TI  - Transient expression of beta-NADPH diaphorase in developing rat dorsal root
      ganglia neurons.
AB  - We report here that during early fetal rat development, most, if not all, dorsal
      root ganglion (DRG) cells were stained by the beta-NADPH diaphorase histochemical
      reaction, indicating that they expressed nitric oxide synthase. During late fetal
      development, most DRG cells lost their diaphorase activity, but a small subset
      (located in all DRGs, but primarily in mid-thoracic DRGs) remained diaphorase
      positive in adult animals. The transient expression of this enzyme suggests that
      nitric oxide may play a role during development that differs from its function in
      mature cells.

PMID- 7511996
TI  - Different forms of insulin-like growth factor-binding protein-3 detected in serum
      and seminal plasma by immunofluorometric assay with monoclonal antibodies.
AB  - Monoclonal antibodies against recombinant insulin-like growth factor-binding
      protein-3 (IGFBP-3) were produced to study the various forms of IGFBP-3 and to
      develop a specific immunofluorometric assay. We tested seven antibodies that
      showed no cross-reactions with the other five human IGFBPs. By immunoblotting,
      the main bands in normal serum were seen at > 90, 45, 41, 29, and 25 kDa. In
      pregnancy serum, the 29-kDa was stronger, and the double band at 41-45 kDa was
      weaker or totally absent. We characterized two immunofluorometric assays. IGF-I
      had no effect on either assay. Added IGF-II lowered the amount of recombinant
      IGFBP-3 measured by the 5C11/7F8 assay, but not by the 1B6/5C11 assay. In normal
      serum and follicular fluid, IGFBP-3 measurements were lower by the 5C11/7F8
      assay, but in most pregnancy sera and amniotic fluids the assays gave similar
      results. The 5C11/7F8 assay also detected IGFBP-3 in seminal plasma, whereas the
      1B6/5C11 assay did not. We conclude that the results of IGFBP-3 measurement
      depend on the antibodies used, and that different antibodies are suitable for the
      IGFBP-3 measurement in different body fluids.

PMID- 7511997
TI  - Two-site enzyme immunoassay of cholesteryl ester transfer protein with monoclonal
      and oligoclonal antibodies.
AB  - We developed a sandwich-type enzyme immunoassay to measure cholesteryl ester
      transfer protein (CETP) mass in human plasma. A specific monoclonal antibody (TP
      4) that recognizes an epitope located in the C-terminal domain was used for
      antigen capture and an anti-CETP peptide antibody directed against the 290-306
      residue was used for detection. Bound antibodies were revealed with an antibody
      peroxidase conjugate specific for rabbit IgG. The presence of 10 mL/L Triton X
      100 in the incubation buffer increased antigen exposure of CETP in plasma. The
      curves for CETP in standard plasma and partially purified CETP were parallel.
      This technique is rapid (results within 6 h), accurate, precise (mean intra- and
      interassay CVs 3.6% and 8.4%, respectively), and simple to perform. Assay
      sensitivity is at microgram concentrations, with a working range of 20-200
      micrograms/L. In 40 normolipidemic healthy subjects, the mean CETP concentration
      in plasma was 1.1 +/- 0.4 mg/L. A strong correlation between CETP concentration
      and CETP activity (r = 0.91, n = 42) was observed. In plasma, the bulk of CETP
      was found in high-density lipoprotein fractions. Therefore, this assay may be a
      useful tool for investigations of CETP and its significance in relevant diseases.

PMID- 7511999
TI  - The 1993 San Diego Conference: Beyond DNA Probes. November 18-20, 1993.
      Proceedings and abstracts.

PMID- 7511998
TI  - Measuring c-erbB-2 oncogene amplification in fresh and paraffin-embedded tumors
      by competitive polymerase chain reaction.
AB  - We present an original application of competitive polymerase chain reaction (PCR)
      for measuring oncogene amplification in DNA from human tumors by simultaneous PCR
      amplification of genomic DNA with fixed amounts of an internal standard
      (competitor DNA). Competitors share the same sequence as the target genes but
      contain an additional 15- to 20-base-pair insert, which allows resolution of the
      amplified products after polyacrylamide gel electrophoresis and ethidium bromide
      staining. The gene copy number is derived from the ratio between the intensities
      of the bands corresponding to the amplified products. Using this procedure, we
      measured c-erbB-2 amplification in breast and bladder carcinomas in both fresh
      tumor tissues and paraffin-embedded tissue samples and assessed the precision,
      sensitivity, and accuracy of the assay. Competitive PCR is a simple, reliable,
      and accurate method for the evaluation of c-erbB-2 amplification and is
      potentially suitable for use in the clinical laboratory.

PMID- 7512000
TI  - Expression and nature of the alkaline phosphatase gene in cultured osteosarcoma
      cells.
AB  - The molecular mechanism for the differences in specific activity of alkaline
      phosphatase in six human osteosarcoma cell lines was investigated. Five of the
      lines expressed only the tissue-non-specific or liver/bone/kidney isoenzyme of
      alkaline phosphatase. The sixth line had the lowest levels of alkaline
      phosphatase and this was determined to be a mixture of liver/bone/kidney
      isoenzyme and at least one other form. The mRNA of liver/bone/kidney alkaline
      phosphatase was identified by Northern analysis in the three cell lines that
      expressed the largest amount of alkaline phosphatase catalytic activity. This
      mRNA was indistinguishable in size from that seen in control mRNA from normal
      kidney (2.5 kb). Southern analysis demonstrated that EcoRI or HindIII restriction
      fragment patterns and the intensity of the bands, of the liver/bone/kidney
      alkaline phosphatase gene in the osteosarcoma cell lines were identical to that
      of the control DNA from normal peripheral blood leukocytes. Thus, the gene coding
      for liver/bone/kidney alkaline phosphatase appears to be intact in all of these
      osteosarcoma cells and it is unlikely that rearrangement, deletion or
      amplification of the gene is responsible for its activation or inactivation. Slot
      blot analysis revealed varying amounts of the transcripts of the
      liver/bone/kidney isoenzyme in each of the cell lines. The best fit line of a
      plot of the log of the level of mRNA of alkaline phosphatase vs. the log of the
      specific activity of liver/bone/kidney alkaline phosphatase was constructed. This
      gave a Pearson correlation coefficient of 0.92 (P < 0.008), demonstrating a
      significant relationship between the two variables. It is likely that the
      regulation of alkaline phosphatase activity is at the transcriptional process
      rather than the translational or post-translational processes and that the
      specific activity of the enzyme may be controlled by the amount of steady-state
      mRNA of the liver/bone/kidney isoenzyme.

PMID- 7512001
TI  - High performance liquid chromatographic profiling of tryptophan and related
      indoles in body fluids and tissues of carcinoid patients.
AB  - A high performance liquid chromatographic method with quaternary gradient elution
      and fluorometric detection was developed for profiling of tryptophan (TRP), 5
      hydroxytryptophan, serotonin (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) in
      urine, platelet-rich plasma and (tumour) tissue of patients with carcinoid
      tumours. Prior to injection, urine samples were diluted and filtered. Platelet
      rich plasma and tissue homogenates were prepurified by C18 solid phase
      extraction. Detection limits were approx. 2 pmol. Results of urinary 5-HT and 5
      HIAA compared favourably with those of single component analyses. No consistent
      diurnal variations were found for TRP, 5-HT and 5-HIAA in 12-h urine samples from
      15 healthy adults. Abstinence of 5-HT-rich foods reduced urinary levels of 5-HT
      and 5-HIAA. C18 extraction of indoles from protein-containing matrices was
      studied in platelet-rich plasma. Although time-consuming and complicated for
      daily routine use, the present approach offers particular advantages over single
      component analyses in the study of TRP metabolism in patients with carcinoid
      tumours.

PMID- 7512002
TI  - Enzyme immunoassay of serum type IV collagen in anti-HCV positive chronic liver
      diseases.

PMID- 7512003
TI  - A new simple and rapid dual assay for AFP and free beta hCG in screening for Down
      syndrome.
AB  - We have evaluated a simple and rapid 2-step dual-label assay (DELFIA) for
      alphafetoprotein (AFP) and free beta subunit of human gonadotropin (hCG beta) in
      second-trimester screening for Down syndrome. Based on stored serum samples from
      1059 normal control pregnancies and 72 cases of Down syndrome, we have found the
      mean Multiple of Median (MoM) for AFP and free hCG beta to be 0.70 and 2.31,
      respectively. This is slightly but not significantly better than the values for
      the separate assay for AFP (0.76 MoM) and for intact hCG (2.11 MoM). However, the
      dual assay is much simpler than the separate assays and therefore prospective
      comparison trials should be carried out.

PMID- 7512004
TI  - Elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and sE
      selectin levels in bronchial asthma.
AB  - Adhesion molecules such as ICAM-1 and E-selectin have been shown to play
      important roles in the production of allergic inflammation. In the present study,
      we measured serum soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-selectin)
      levels by ELISA in 42 patients with bronchial asthma (22 atopic and 20 non
      atopic) during asthma attacks and in stable conditions in order to assess the
      state of ICAM-1 and E-selectin in allergic inflammation. Both serum sICAM-1
      levels and serum sE-selectin levels in sera obtained during bronchial asthma
      attacks were higher than those in sera obtained in stable conditions. These
      findings were observed regardless of atopic status. To examine the regulatory
      mechanism in the elevation of serum sICAM-1 and sE-selectin levels, serum tumour
      necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels
      in sera obtained during bronchial asthma attacks were higher than those in sera
      obtained in stable conditions. There was a correlation between the nature of
      change in serum TNF-alpha levels and the nature of change in serum sICAM-1 levels
      or serum sE-selectin levels, though serum TNF-alpha levels did not correlate with
      serum sICAM-1 levels or serum sE-selectin levels. These results suggest that
      higher levels of sICAM-1 and sE-selectin during asthma attacks may reflect the up
      regulation of ICAM-1 and E-selectin expression in allergic inflammation, and that
      the soluble form of these adhesion molecules may be useful markers for the
      presence of allergic inflammation. TNF-alpha is shown to enhance the expression
      and release of ICAM-1 and E-selectin in vitro, however; the regulatory mechanism
      in the elevation of serum sICAM-1 and sE-selectin levels remains to be clarified.

PMID- 7512005
TI  - Elevated levels of soluble CD14 in serum of patients with systemic lupus
      erythematosus.
AB  - A soluble form of CD14 (sCD14) was assessed with an ELISA assay in the serum of
      the following three clinical groups: 35 patients with an inactive phase of
      systemic lupus erythematosus (SLE), 17 patients with SLE relapses, and 65 normal
      healthy volunteers. Increased levels of sCD14 were observed in all patients
      suffering from SLE compared with normal controls. In addition, patients with
      active SLE revealed higher serum concentrations of sCD14 (median 6.9 mg/l) than
      patients under remission (4.1 mg/l; P < 0.0001). Serum values of sCD14 correlated
      neither with the number of peripheral blood monocytes bearing the CD14 membrane
      antigen, nor with serum concentrations of IL-1 beta. Serum sCD14 was compared
      with other clinical parameters used to monitor the clinical course of patients
      with SLE, among them complement C3, anti-dsDNA antibodies and soluble IL-2
      receptor (sIL-2R). A good correlation emerged between sCD14 and C3 as well as sIL
      2R concentrations, but sCD14 and anti-dsDNA titres disclosed no significant
      correlation in both groups of patients with SLE. Serial studies in patients with
      severe SLE showed that serum sCD14 closely parallels the clinical course as
      defined by an activity score. Our data suggest that serum sCD14 represents a
      promising parameter to monitor disease activity in patients with SLE.

PMID- 7512006
TI  - Characterization of EN4 monoclonal antibody: a reagent with CD31 specificity.
AB  - EN4 MoAb was originally described as a MoAb that reacts specifically with human
      endothelial cells, and the reagent was not assigned to any of the presently known
      CD. Here, we provide evidence indicating that EN4 reacts with the CD31 antigen.
      Thus, EN4 stains strongly murine fibroblasts transfected with the human CD31
      gene. Furthermore, SDS-PAGE analysis of immunoprecipitates of cell lysates from
      surface-iodinated Jurkart T cells demonstrated that EN4 and reference CD31 MoAb
      recognized the same antigen, of 130 kD mol. wt. Finally, both EN4 and CD31 gave
      the same pattern of reactivity when tested on tonsillar or peripheral blood
      lymphoid cells by FACS analysis or by immunohistochemistry on sections of a
      variety of human tissues. EN4, however, proved consistently more efficient than
      the reference anti-CD31 MoAb as judged by both the intensity of fluorescence or
      of tissue staining. This property has thus allowed a better characterization of
      the tissue and cellular distribution of CD31.

PMID- 7512007
TI  - Human anti-fibronectin antibodies in systemic lupus erythematosus: occurrence and
      antigenic specificity.
AB  - Sera from patients with connective tissue diseases exhibit autoantibodies to a
      spectrum of extracellular matrix proteins. Antibodies binding to solid phase
      bovine fibronectin (Fn) were investigated by ELISA in patients with systemic
      lupus erythematosus (SLE). Sera showing binding of 2 s.d. above the mean of the
      normal human control were considered positive and 43/150 SLE sera (28.7%)
      demonstrated such binding. These antibodies were mainly IgG and IgA as determined
      by isotype-specific ELISA. Specificity studies on selected positive sera revealed
      that binding was inhibited by preincubation with soluble Fn, but not with
      thyroglobulin or type 1 collagen. The binding was demonstrated not to be related
      to interactions with rheumatoid factor, complement components or immune
      complexes. Additional studies to determine which Fn fragment is bound by
      naturally occurring anti-Fn antibodies demonstrated that the binding was
      predominantly to the 30-kD collagen binding domain (CBD) of Fn molecule.
      Inhibition studies using 120-kD, 40-kD and 30-kD Fn fragments confirmed that this
      binding site was the 30-kD CBD.

PMID- 7512008
TI  - Experimental arthritis induced by continuous infusion of IL-8 into rabbit knee
      joints.
AB  - To determine the roles of IL-8 in inflammatory synovitis, examination was made of
      the results of continuously injecting human recombinant IL-8 into the knee joints
      of New Zealand while rabbits. Recombinant human IL-8 was infused continuously
      into the joint cavity at 75 ng/h for 14 days by a polypropylene catheter
      connected to a mini-osmotic pump implanted in each rabbit. Infiltration of
      inflammatory cells into joint cavity and histopathological changes in synovial
      tissue were examined at 7 and 14 days following the start of infusion. The
      continuous infusion of IL-8 for 14 days led to severe arthritis characterized by
      apparent erythema and joint pain, the accumulation of leucocytes, infiltration of
      mononuclear cells in synovial tissue, and marked hypervascularization in the
      synovial lining layer. IL-8 may be a factor which can contribute to the
      inflammatory process of chronic arthritis by mediating leucocyte recruitment and
      hypervascularization in inflamed joints.

PMID- 7512009
TI  - Impaired granulocyte oxidative burst and decreased expression of leucocyte
      adhesion molecule-1 (LAM-1) in patients with Wegener's granulomatosis.
AB  - Neutrophils are the target of autoantibodies in Wegener's granulomatosis (WG). In
      this study, granulocyte function and surface marker expression were investigated
      in patients with WG. The oxidative burst in response to phorbol myristate acetate
      (PMA) was tested with granulocytes of 25 patients with histologically proven WG.
      A significantly diminished percentage of oxygen radical-producing cells was found
      in patients with active disease. Surface antigen expression of CD11b and LAM-1
      was analysed on granulocytes of 20 patients with WG. Whereas the expression of
      CD11b was normal, surface expression of LAM-1 was decreased in nine cases with
      WG. The decrease of LAM-1 correlated with disease activity. Phagocytosis of
      Escherichia coli was tested in 10 patients with WG, and normal values were found
      in all cases. We conclude that down-regulation of LAM-1 may be a marker of
      disease activity in WG. The altered response to PMA may indicate functional
      changes in granulocyte reactivity due to autoantibody-induced damage of the
      granulocyte membrane.

PMID- 7512011
TI  - Characterization of monoclonal antibodies recognizing bovine bone osteoglycin.
AB  - Six monoclonal antibodies (mAb) are described that bound to the bovine bone
      glycoprotein, osteoglycin. The protein osteoglycin was originally called
      Osteoinductive Factor (OIF). The antibodies were characterized with respect to
      their reaction patterns in Western blots, indirect immunoprecipitation, and
      binding epitope. The antibodies bound to one of two sequential determinants,
      either residues 62-76 or 95-105, in the C-terminal region of mature osteoglycin.
      One mAb, 2C11, was found to be useful for affinity purification of osteoglycin.
      Another mAb, 3B2, was able to immunohistochemically stain osteoblasts,
      osteocytes, chondrocytes, occasional osteoclasts and nail bed epithelial cells in
      rat neonatal forelimb. The mAbs will provide an essential tool for the further
      characterization of this unique glycoprotein.

PMID- 7512012
TI  - Keratan sulfate inhibits its release in rabbit chondrocyte.
AB  - Keratan sulfate (KS) is one of the major glycosaminoglycans in cartilage matrix
      proteoglycan. We find that exogenously added KS totally blocks keratanase
      sensitive glycosaminoglycan release measured by radiolabeled ligand. We also find
      that KS release is potentially inhibited by its own presence as measured by
      ELISA. When KS is digested with keratanase before its addition to the medium, its
      inhibitory effect on KS secretion is partially blocked. Exogenously added KS
      promotes the accumulation of the KS epitope in the cell layer. These data suggest
      that KS negatively regulates its own secretion.

PMID- 7512010
TI  - B7/BB1 provides an important costimulatory signal for CD3-mediated T lymphocyte
      proliferation in patients with systemic lupus erythematosus (SLE).
AB  - Successful T cell activation via the T cell receptor (TCR)/CD3 complex requires
      at least one contact-dependent second signal delivered by costimulatory
      molecules, including the B7/BB1 molecule, that are present on antigen-presenting
      cells (APC). SLE is characterized by multiple complex lymphocyte abnormalities of
      undefined molecular origin. It is currently unclear whether an intrinsic defect
      of T cell or an underlying APC dysfunction is responsible for defective in vitro
      proliferation of T cells from patients with SLE. We planned the present
      experiments to ask whether the TCR/CD3-mediated and B7/BB1-costimulated T cell
      proliferation is normal in these patients. We used enriched T cell populations
      that were stimulated with an anti-CD3 MoAb in the presence of controlled
      quantities of functional B7/BB1 antigen. Freshly isolated T cells from 17 SLE
      patients (10 and seven patients with either active or inactive disease,
      respectively) and 11 normal individuals were cocultured with irradiated B7/BB1
      transfected P815 cells or parental P815 cells in the presence of OKT3 MoAb at
      optimal and suboptimal concentrations for 2.5-7 days. Normal or SLE T cells
      responded similarly to stimulation via anti-CD3, in the absence of B7/BB1
      antigen. A several-fold increase in T cell proliferation in the presence of
      B7/BB1 antigen was observed. Proliferation was inhibited in the presence of anti
      B7/BB1 MoAb, but not with control MoAbs. Interestingly, dose-response curves and
      time kinetics of B7/BB1 costimulation were similar in T cells from patients with
      either active or inactive SLE at the time of study, and normal individuals. In
      addition, no differences in the IL-2 receptor release by T cells cultured under
      these conditions were observed between SLE patients and normal individuals. These
      results demonstrate that CD28 signalling is not intrinsically impaired in
      patients with SLE; further studies to investigate whether abnormal B7/BB1
      expression is involved in the autoimmune process are needed.

PMID- 7512013
TI  - Identification of hyaluronan binding proteins using a biotinylated hyaluronan
      probe.
AB  - A method for detecting hyaluronan (HA)-binding proteins in transblot assays using
      biotinylated HA (BHA) is described. Some of the binding characteristics of a
      novel HA receptor termed RHAMM (Receptor for HA-Mediated Motility) are
      characterized using this assay. The method is also used to detect other HA
      binding proteins in tissue homogenates. This method is semiquantitative, rapid,
      reproducible, sensitive and therefore of potential use in identifying the levels
      of HA-binding proteins in different cells and tissues.

PMID- 7512014
TI  - Inaccessibility of the Euplotes telomere binding protein.
AB  - The telomere binding protein (TP) from the macronucleus of the ciliate Euplotes
      eurystomus was purified by removal of tenaciously bound DNA with hydroxylapatite,
      and the purified TP partially sequenced. Rabbit antiserum was generated against a
      synthetic peptide of 14 amino acids at the amino-terminus of the TP. This
      antiserum was employed to examine the accessibility of TP antigenic determinants
      in nuclei and chromatin. Immunofluorescent staining of isolated macronuclei
      revealed only weak reactivity with specific antiserum. Reactivity within
      replication bands was demonstrated, and could be augmented by preparation of
      nuclear scaffolds. Employing a dot immunoblot analysis, the amino-terminal
      antigenic determinants of TP were revealed after extraction of histone H1 (and
      some nonhistones). A different aspect of TP inaccessibility was demonstrated by
      immunoblot analysis of trypsin-treated macronuclei and chromatin; TP was
      considerably less susceptible to digestion by trypsin than were histones H1 and
      H3. The relative inaccessibility of TP was not a consequence of chromatin higher
      order structure, since soluble macronuclear chromatin in low salt exhibited the
      same burying of antigenic determinants by dot blot analysis, and the same
      decreased susceptibility to trypsin, as did isolated nuclei. Electron microscopy
      of soluble macronuclear chromatin spread in low salt revealed that most telomeres
      appear unfolded, without stable higher-order structure. The mechanisms for the
      relative inaccessibility of TP are not yet known, but probably arise as a
      consequence of the strong interactions of TP with the telomere nucleotide
      sequence and additional interactions of TP with various chromatin proteins,
      perhaps including histone H1.

PMID- 7512016
TI  - Nitric oxide mediates inhibitory nerve effects in human esophagus and lower
      esophageal sphincter.
AB  - The effect of inhibition of nitric oxide synthase on nonadrenergic,
      noncholinergic nerve-mediated responses in circular smooth muscle of the human
      esophageal body and lower esophageal sphincter (LES) was examined in vitro.
      Tissues were obtained from 10 patients (eight esophageal resection for cancer,
      two transplant donors). Muscle strips from the LES developed significant
      spontaneous tension (11.6 +/- 2.1 mN/mm2, N = 6) and relaxed in response to
      electrical stimulation. The nitric oxide synthase inhibitor, N omega-nitro-L
      arginine (NNA), at 10(-5) M, inhibited the relaxation, but had no significant
      effect on the spontaneous tension (13.0 +/- 2.6 mN/mm2, P = 0.07). Esophageal
      body strips developed little spontaneous tension, demonstrated an "off"
      contraction following the cessation of the electrical stimulus, and when
      contracted with 10(-5) M carbachol, relaxed during electrical stimulation. NNA
      (10(-5) M) inhibited the off contraction and the relaxation seen after carbachol
      and unmasked a prominent intrastimulus contraction. This intrastimulus
      contraction was enhanced by eserine and inhibited by atropine and tetrodotoxin.
      NNA showed similar potency in the esophageal body and LES and its effects were
      reversed by L-arginine, but not D-arginine. The results indicate that nitric
      oxide is an important mediator for nonadrenergic, noncholinergic nerve effects in
      the human esophagus and lower esophageal sphincter.

PMID- 7512015
TI  - Effects of FK506, an immunosuppressive agent, on genesis of water-immersion
      stress-induced gastric lesions in rats.
AB  - We examined the effects of FK506, an immunosuppressive agent, on the genesis of
      water immersion stress-induced gastric lesions in rats. Using high-performance
      liquid chromatography, four kinds of prostaglandins, ie, 6-keto-prostaglandin F1
      alpha, prostaglandin F2 alpha, prostaglandin E2, and prostaglandin D2, were
      detected, and no leukotrienes were detected in gastric mucosa in rats without
      stress. After 6 hr of stress, gastric lesions developed with decreases in all
      prostaglandin contents, and the emergence of peptide leukotrienes was observed.
      Intramuscular administration of FK506 (0.1, 0.25, 0.5, 1.0, and 2.0 mg/kg)
      reduced lesion index dose-dependently. Administration of FK506 at doses over 0.25
      mg/kg decreased all prostaglandin contents, but did not affect the increase in
      leukotriene contents. Pretreatment with famotidine or omeprazole reduced lesion
      index, and the protective effects were equivalent to those of 1.0 mg/kg of FK506,
      although FK506 did not affect gastric secretion during water-immersion stress.
      Water-immersion stress did not change the activities of xanthine oxidase in
      either stomach or serum. Polyoxyethylene-modified superoxide dismutase did not
      prevent gastric lesions. Water-immersion stress significantly increased
      myeloperoxidase activity in gastric mucosa, and FK506 reduced the increase in
      myeloperoxidase activity induced by stress. From our results, other factors
      besides gastric acid secretion and tissue eicosanoid contents, such as
      chemoattractant factor, might also be involved in the genesis of water-immersion
      stress-induced gastric lesions in rats.

PMID- 7512017
TI  - Preventive effect of immunosuppressive agents against indomethacin-induced small
      intestinal ulcers in rats.
AB  - The mechanism of nonsteroidal antiinflammatory drug-induced intestinal ulcers is
      not clearly understood. To evaluate whether immunosuppressants have a preventive
      effect against indomethacin-induced gastrointestinal damage, we investigated the
      effects of prednisolone, cyclosporin, and the newly developed immunosuppressant
      FK-506 in intracolonically indomethacin-treated rats: 24 mg/kg of indomethacin,
      administered intracolonically for two days, caused gastric ulcers and two types
      of small intestinal ulcers (longitudinal ulcers and scattered small ulcers).
      Pretreatment with intraperitoneal immunosuppressants reduced the size of gastric
      ulcers. Both cyclosporin (10 mg/kg) and FK-506 (1 mg/kg, 2 mg/kg) treatments
      significantly reduced the incidence and the length of the longitudinal ulcers of
      the small intestine when compared to the vehicle-treated controls, whereas
      prednisolone (20 mg/kg) did not show any preventive effect. Furthermore, the
      number of small scattered ulcers of the small intestine was significantly reduced
      by the high dose of FK-506 (2 mg/kg), but not by cyclosporin or prednisolone.
      These findings indicate that immunosuppressants have protective and
      antiinflammatory effects in indomethacin-induced gastroenteropathy, suggesting
      that cytokines may be important mediators in the pathogenesis of enteropathy
      induced by nonsteroidal antiinflammatory drugs.

PMID- 7512018
TI  - Regulation of hepatocyte albumin and alpha 1-acid glycoprotein secretion by
      monokines, dexamethasone, and nitric oxide synthase pathway: significance of
      activated liver nonparenchymal cells.
AB  - To clarify the mechanism involved in regulating the secretion of albumin and
      alpha 1-acid glycoprotein by rat hepatocytes, we studied hepatocyte culture and
      cocultures of hepatocyte and liver nonparenchymal cells. The secretion of alpha 1
      acid glycoprotein by hepatocytes was stimulated and that of albumin was inhibited
      by combinations of dexamethasone and monokines, especially by dexamethasone and
      interleukin-6. The secretion of these proteins was equally inhibited during
      stimulation by lipopolysaccharide in cocultures. The inhibitory effect of
      sinusoidal endothelial cells was smaller than that of Kupffer cells. This
      inhibition was partially abolished by blocking the nitric oxide synthase pathway
      in cocultured cells and was completely abolished by dexamethasone. In conclusion,
      the secretion of albumin and alpha 1-acid glycoprotein by hepatocytes was
      regulated by monokines, dexamethasone, and the inducible nitric oxide synthase
      pathway in hepatocytes and liver nonparenchymal cells in vitro.

PMID- 7512019
TI  - The metabolism and excretion of risperidone after oral administration in rats and
      dogs.
AB  - The metabolism and excretion of risperidone (RIS; 3-[2-[4-(6-fluoro-1,2
      benzisoxazole-3-yl)-1-piperidinyl]ethyl]-6,7,8,9- tetrahydro-2-methyl-4H
      pyrido[1,2-a]pyrimidin-4-one), a novel antipsychotic drug, were studied after
      single po administration of radiolabeled RIS to rats and dogs. In rats, the
      excretion of the radioactivity was very rapid. The predominant excretion in rat
      feces (78-82% of the dose) was related to an extensive biliary excretion of
      metabolites (72-79% of the dose), only a small part of which underwent
      enterohepatic circulation. In dogs, about 92% of the dose had been excreted after
      one week, and the fractions recovered in the urine and feces were comparable.
      Only a few percent of a po dose was excreted as unchanged RIS in rats as well as
      in dogs. Major metabolic pathways of RIS in rats and dogs were the same as those
      in humans. The main pathway was the hydroxylation at the alicyclic part of the
      6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one moiety. The resulting
      9-hydroxy-risperidone (9-OH-RIS) was the main metabolite in the excreta of dogs.
      In rats, the metabolism was more extensive, resulting in dihydroxy-RIS and
      hydroxy-keto-RIS, which were eliminated mainly via the bile. However, in male and
      in female rats, just as in dogs and humans, the active metabolite 9-OH-RIS was by
      far the main plasma metabolite. Other major metabolic pathways were the oxidative
      dealkylation at the piperidine nitrogen and the scission of the isoxazole in the
      benzisoxazole ring system. The latter pathway appeared to be effected primarily
      by the intestinal microflora.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512021
TI  - [Biochemical analyses in dogs of the beagle breed. 1. The content of DNA, RNA and
      protein in 13 tissues in ages from one day to 18 months].
AB  - In dogs of the race "beagle" in the age of one day, of 28 days as well as in that
      of 6 and 18 months the content of DNA, RNA and protein in 13 tissues was
      analysed. The wet weight:DNA-, the protein:DNA- and the RNA:DNA-ratios were
      calculated. The growth of the various tissues by hyperplasia and hypertrophy is
      described.

PMID- 7512020
TI  - FK 506 metabolism in male and female rat liver microsomes.
AB  - The main metabolite of the immunosuppressant FK 506 in hepatic microsomes from
      male and female Sprague-Dawley rats was identified by mass spectrometry as an O
      desmethyl derivative. The rate of formation of the metabolite exhibited
      saturation kinetics in the range of 0.6-40 microM with Vmax and KM equal to 0.66
      +/- 0.47 nmol/min/mg protein and 24 +/- 18 microM, respectively, for microsomes
      from male rats, and 0.28 +/- 0.15 nmol/min/mg protein and 24 +/- 16 microM,
      respectively, for microsomes from female rats. CYP3A enzymes are thought to be
      responsible for metabolizing FK 506 in male rats. Because untreated female rats
      show no classical CYP3A activity, our work suggests that other CYP enzymes
      metabolize FK 506 in untreated female rats. O-Desmethyl FK 506 did not cross
      react in the standard clinical ELISA assay for FK 506. This suggests that
      demethylation had occurred at the C13-methoxy group.

PMID- 7512022
TI  - Early transcription in Caenorhabditis elegans embryos.
AB  - We have analysed early transcription in devitellinized, cultured embryos of the
      nematode Caenorhabditis elegans by two methods: measurement of [32P]UTP uptake
      into TCA-precipitable material and autoradiographic detection of [3H]UTP
      labelling both in the presence and absence of alpha-amanitin. RNA synthesis was
      first detected at the 8- to 12-cell stage, and alpha-amanitin sensitivity also
      appeared at this time, during the cleavages establishing the major founder cell
      lineages. The requirements for maternally supplied versus embryonically produced
      gene products in early embryogenesis were examined in the same culture system by
      observing the effects of alpha-amanitin on cell division and the early
      stereotyped lineage patterns. In the presence of high levels of alpha-amanitin
      added at varying times from two cells onward, cell division continued until
      approximately the 100-cell stage and then stopped during a single round of cell
      division. The characteristic unequal early cleavages, orientation of cleavage
      planes and lineage-specific timing of early divisions were unaffected by alpha
      amanitin in embryos up to 87 cells. These results indicate that embryonic
      transcription starts well before gastrulation in C. elegans embryos, but that
      although embryonic transcripts may have important early functions, maternal
      products can support at least the mechanics of the first 6 to 7 cell cycles.

PMID- 7512024
TI  - Blockade of cardiac outwardly rectifying K+ channels by TEA and class III
      antiarrhythmics--evidence against a single drug-sensitive channel site.
AB  - Elementary K+ currents through cardiac outwardly rectifying K+ channels were
      recorded in inside-out patches excised from cultured neonatal rat cardiocytes at
      19 degrees C and at 9 degrees C. By studying the inhibitory effects of
      tetraethylammonium (TEA), quinidine and verapamil, the properties of this novel
      type of K+ channel were further characterized. Internal TEA (50 mmol/l) evoked a
      reversible decline of i unit to 62.7 +/- 2.7% of control (at -7 mV), without
      significant changes of open state kinetics, indicating a blockade of the open K+
      pore with kinetics too fast to be resolvable at 1 kHz. This TEA blockade was e
      fold voltage-dependent, with a decrease of the apparent KD(TEA) from 102 mmol/l
      at -37 mV to 65 mmol/l at +33 mV and, furthermore, became accentuated on lowering
      the internal K+ concentration. Thus, TEA competes with the permeant K+ for a site
      located in some distance from the cytoplasmic margin, within the K+ pore.
      Quinidine (100 mumol/l), like verapamil (40 mumol/l) reversibly depressed i unit
      to about 80% of the control value (at -7 mV), but drug-induced fast flicker
      blockade proved voltage-insensitive between -27 mV and +23 mV. These drugs gain
      access to a portion of the pore distinct from the TEA binding site whose
      occupancy by drugs likewise blocks K+ permeation. Both drugs showed a greater
      potency to depress Po which, with quinidine, decreased reversibly to 38.6 +/-
      11.1% (at -7 mV) and, with verapamil to 24.9 +/- 9.1% (at -7 mV), mainly by an
      increase of the prolonged closed state (C2). This alteration of the gating
      process also includes a sometimes dramatic shortening of the open state. Most
      probably, cardiac K+(outw.-rect.) channels possess a second drug-sensitive site
      whose occupancy by quinidine or verapamil may directly or allosterically
      stabilize their non-conducting configuration.

PMID- 7512023
TI  - Muscarinic inhibition of high-voltage-activated calcium channels in excised
      membranes of rat hippocampal neurons.
AB  - The effect of muscarine on voltage-gated calcium channels was investigated in
      outside-out patches from rat hippocampal neurons in culture. By clamping the
      excised patches at -60 mV holding potential, single and multiple Ca channel
      currents were recorded, and these displayed features similar to the high-voltage
      activated Ca current, with unitary conductance of 6.4 pS in 50 mM external Ca2+.
      These channels turned out to be insensitive both to Bay K 8644 and to omega
      conotoxin. In excised patches muscarine caused a marked reduction in the
      probability of opening of this class of Ca channels without significant changes
      in the unitary current amplitude. Interestingly, the degree of current inhibition
      was reduced by depolarization, thus suggesting a voltage-dependent inhibitory
      action of the agonist. We conclude that in hippocampal neurons one of the
      possible ways of HVA Ca channel modulation by muscarine occurs through activation
      of a substratum localized within the plasma membrane of the cell, independent of
      the involvement of diffusible intracellular messengers.

PMID- 7512025
TI  - The conformation of linear gramicidin is sequence dependent. A monolayer and
      infrared study.
AB  - A comparative monolayer and infrared study of analogues of gramicidin A
      containing either tyrosines or naphthylalanines instead of tryptophans indicates
      that the nature of the aromatic residues influences the favoured conformation of
      the peptides. Polar residues favour the single stranded IIDL helix while non
      polar residues favour the double stranded helix. For partly tryptophan to
      naphthylalanine substituted analogues the positions of the substitutions
      orientate the favored conformation. The nature of these substitutions may also
      modify the peptide-lipid interactions.

PMID- 7512026
TI  - Effects of clonidine and IBMX on sulfobromophthalein disposition in rats.
AB  - Clonidine, an alpha 2-adrenoceptor agonist, inhibited the biliary excretion,
      reduced the plasma clearance and increased the hepatic retention of
      sulfobromophthalein (BSP) in a dose related fashion in rats. The maximal effects
      of clonidine on BSP disposition occurred about 4 h after pretreatment. The
      effects of clonidine on biliary excretion and hepatic retention of BSP were
      retained following laparotomy (with or without bile duct cannulation); however,
      the effect of clonidine on plasma disappearance profile was not retained
      following abdominal surgery. Isobutylmethylxanthine (IBMX) affected BSP
      disposition in a similar fashion as clonidine, in rats without bile duct
      cannulation only; no effect of IBMX could be observed in bile duct cannulation
      rats. Yohimbine, an alpha 2-adrenoceptor antagonist, reversed the effects of
      clonidine, but not of IBMX, on BSP disposition. It thus seems that clonidine and
      IBMX exert their effects on BSP disposition by different mechanisms and probably
      at different sites.

PMID- 7512027
TI  - Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on
      human monocytes.
AB  - There is evidence that interleukin -10(IL-10) interferes with the costimulatory
      properties of antigen-presenting cells and, thereby, inhibits their ability to
      induce T cell activation. To determine whether this effect might involve
      modulation of the expression of accessory molecules, we analyzed by flow
      cytometry the influence of human IL-10 on the basal expression of intercellular
      adhesion molecule 1 (ICAM-1) as well as on the interferon gamma (IFN-gamma)
      induced up-regulation of ICAM-1 and B7 at the surface of human monocytes. IL-10
      inhibited both the basal expression and the IFN-gamma-induced ICAM-1 up
      regulation. IL-10 also reduced B7 up-regulation on IFN-gamma-stimulated
      monocytes. The inhibitory effect of IL-10 both on ICAM-1 and B7 expression was
      shown to be dose dependent. We conclude that the ability of IL-10 to decrease
      both ICAM-1 and B7 expression on monocytes might contribute to its
      immunosuppressive properties.

PMID- 7512028
TI  - B cells regulate expression of CD40 ligand on activated T cells by lowering the
      mRNA level and through the release of soluble CD40.
AB  - The expression of CD40 ligand (CD40L) on activated T cells (CD4+ T cell clone
      MT9) is diminished when the T cells are cultured in the presence of B cells. This
      effect, observed both with normal tonsil B cells and with the B cell line JY, was
      detected after 6 h and sustained at least until 18 h of co-culture. Analysis of
      mRNA showed that CD40L mRNA levels were not modified after 6 h, but were
      significantly down-regulated after 18 h of co-culture with B cells. Although
      CD40L expression could not be detected by a CD40-Fc chimera, the molecule was
      still expressed at the membrane as shown with a polyclonal antiserum against
      CD40L (anti-TRAP). In addition, T cells activated in the presence of B cells were
      stained by a polyclonal antiserum against CD40, without the appearance of CD40
      mRNA. These results indicated that a soluble form of CD40 (sCD40) bound to the
      expressed CD40L on T cells. The existence of sCD40 was confirmed by detection of
      sCD40 in B cell supernatants using a specific enzyme-linked immunosorbent assay.
      Collectively, these data show that B cells can regulate the expression of CD40L
      on activated T cells at least by two different mechanisms.

PMID- 7512029
TI  - Preferential pairing of T and B cells for production of antibodies without
      covalent association of T and B epitopes.
AB  - T cell from H-2b mice recognize at least 12 sequence regions on the Torpedo
      acetylcholine receptor (TAChR) alpha, gamma and delta subunits. Immunization of
      C57BL/6 mice with individual synthetic TAChR sequences known to contain CD4+
      epitopes resulted in most cases (10 out of 12 peptides) in anti-peptide antibody
      (Ab) production, indicating that short TAChR sequences contain both CD4+ and B
      epitopes. Immunization of C57BL/6 mice with a mixture of a CD4+ epitope peptide,
      from the TAChR or from an unrelated protein, plus another TAChR sequence forming
      a "pure" B epitope (T alpha 63-80), induced in most cases anti-peptide Ab and
      CD4+ cell sensitization only against the peptide containing the CD4+ epitope.
      However, when the T epitope peptide T alpha 360-378 was co-injected with the B
      epitope, Ab were also produced against the B epitope peptide. Injection of the
      individual peptides T alpha 360-378 and T alpha 63-80 at different and distant
      sites along the back of mice elicited sensitization of CD4+ cells and Ab
      production only against peptide T alpha 360-378. Therefore, when optimal
      cooperation between T and B cells occurs, spatial proximity but not covalent
      association of the B and the CD4+ epitope is necessary for production of Ab
      against the B epitope.

PMID- 7512031
TI  - CD5 is associated with the human B cell antigen receptor complex.
AB  - On human B cells the antigen receptor complex is composed of the membrane form of
      the immunoglobulin molecule and the non-covalently associated Ig alpha/beta
      heterodimer. A small subpopulation of normal B cells and chronic lymphocytic
      leukemia B cells express (analogous to T cells) the transmembrane molecule CD5, a
      counterstructure of B cell-specific CD72. Numbers of CD5+ B cells are increased
      in several physiological and pathological conditions. Moreover, CD5+ B cells are
      being held responsible for the production of autoreactive antibodies and seem to
      have signaling characteristics distinct from conventional B cells. On T cells,
      CD5 associates with the T cell receptor CD3 complex and ligation of CD5 leads to
      the generation of co-stimulatory signals, that act on T cell activation. We here
      demonstrate that CD5 is associated with the B cell receptor (BCR) complex and
      serves as substrate for BCR-induced tyrosine kinase activity. Hence, CD5+ B cells
      have a unique potential to modulate BCR signals.

PMID- 7512032
TI  - Preferential expression of interleukin-12 or interleukin-4 by murine bone marrow
      mast cells derived in mast cell growth factor or interleukin-3.
AB  - In this report we demonstrate that murine bone marrow cells cultured in either
      interleukin (IL)-3 or mast cell growth factor (MGF, also known as c-kit ligand
      and stem cell factor) differentially express cytokine genes. Bone marrow cells
      cultured in IL-3 differentiate and proliferate, taking on a mucosal mast cell
      like phenotype. These cells express the IL-4 gene. Bone marrow cells cultured in
      MGF take on a connective tissue mast cell-like phenotype and possess transcripts
      for both of the subunits of the IL-12 cytokine. Bone marrow cells cultured in
      both IL-3 and MGF express the IL-4 gene at lower levels than that seen for the IL
      3 culture alone, but do not possess IL-12 gene transcripts. The level of IL-12
      subunit transcripts derived from the MGF-derived bone marrow cells was compared
      to that found in splenocytes and activated macrophages, the only cells in which
      IL-12 production has been previously documented. Both of the IL-12 subunit
      transcripts were found, compared to a beta-actin control, to be present within
      MGF-derived cells in the same if not higher quantities than the splenocyte or
      macrophage cultures. Mucosal mast cells have been previously implicated in the
      development of the T helper type 2 (TH2) T cell phenotype via their expression of
      IL-4. The finding that the MGF-derived connective tissue-like mast cells possess
      IL-12 transcripts suggests that the development of the TH1 T cell pathway may be
      positively influenced by this type of mast cell.

PMID- 7512030
TI  - Expression and function of the costimulatory molecule B7 on murine Langerhans
      cells: evidence for an alternative CTLA-4 ligand.
AB  - We have previously shown, through transfection experiments, that the murine B7
      (mB7) molecule, a ligand for the CD28 and CTLA-4 receptors, is a sufficient
      costimulatory signal for the antigen-specific and major histocompatibility
      complex (MHC)-restricted activation of murine CD4+ T lymphocytes. In addition to
      mB7, another ligand with affinity for CTLA-4 has been described on spleen cells.
      Here we report our studies on the expression and function of these molecules on
      murine Langerhans cells (LC). Both anti-mB7 monoclonal antibody (mAb) 16-10A1 and
      human CTLA4Ig (hCTLA4Ig), a chimeric fusion protein consisting of the
      extracellular domain of human CLTA-4 and the constant domain of human IgG1,
      detected antigen(s) on cultured but not freshly isolated LC. Preincubation of
      cultured LC with anti-mB7 mAb did not significantly affect binding of hCTLA4Ig to
      these cells. This result demonstrate the existence of at least one other ligand
      for the CLTA-4 receptor on cultured LC. Functional studies revealed that the
      costimulatory activity of LC was inhibited better by hCTLA4Ig than by the anti
      mB7 mAb. This differential effect was seen in the case of both alloreactive and
      antigen-specific, syngeneic T cell responses. These findings suggest that the non
      mB7-ligand for CTLA-4 is functional and participates in the induction of immune
      responses by LC. Importantly, even synergistic combinations of anti-mB7 mAb and
      hCTLA4Ig did not inhibit completely the activity of LC. These findings therefore
      raise the possibility that LC express other costimulatory ligands besides mB7 and
      related family members.

PMID- 7512033
TI  - Activation of CD4+ T cells by delivery of the B7 costimulatory signal on
      bystander antigen-presenting cells (trans-costimulation).
AB  - Increasing evidence in both murine and human systems suggests that the
      interaction of the T cell surface antigens CD28/CTLA4 with their ligand B7 on the
      antigen-presenting cells (APC) is the critical costimulatory pathway involved in
      the induction of maximal T cell activation and the prevention of induction of
      anergy. It has also been demonstrated that efficient induction of clonal
      expansion of normal CD4+ T cells requires the delivery of the T cell receptor
      (TCR) ligand and costimulation by the same APC. We demonstrate here that normal
      murine CD4+ T cells can be efficiently activated by soluble anti-CD3 cross-linked
      by fixed macrophages and by a costimulatory signal delivered by a bystander APC,
      B7-transfected L cells. The major factor which determined the ability of an APC
      to provide costimulation in "trans" was the level of cell surface B7 expression.
      The requirement for B7 costimulation appears to be at initial stage of TCR
      engagement since optimal T cell activation was only observed when TCR triggering
      and B7 costimulatory activity were delivered at same time by different APC.
      Induction of maximal proliferation of both naive CD45RBhi and memory CD45RBlo
      CD4+ T cells was B7 dependent and both populations of cells responded equally
      well to the B7 costimulation delivered in "trans". Furthermore, trans
      costimulation provided by B7 transfected L cells efficiently prevented the
      induction of anergy in normal murine CD4+ T cells induced by anti-CD3 cross
      linked by fixed-resting macrophages. Addition of exogenous interleukin-2 (IL-2)
      and IL-7 to the primary culture in the absence of B7-transfected L cells or
      addition of IL-2 to the culture containing the B7 transfectant and CTLA4Ig
      completely prevented the induction of hyporesponsiveness. These findings raise
      the possibility that in certain pathological states, CD4+ T cells in vivo may be
      activated by costimulation delivered by bystander APC.

PMID- 7512034
TI  - Fas-based lymphocyte-mediated cytotoxicity against syngeneic activated
      lymphocytes: a regulatory pathway?
AB  - To investigate the possibility that Fas-based immune regulation and Fas-based T
      cell-mediated cytotoxicity (F-CMC) are causally related, we explored the latter
      in activated lymphocyte populations. These were shown to contain effector cells
      exerting cytotoxicity via an F-CMC mechanism which could be differentially
      triggered by PMA and ionomycin. F-CMC operated in trans, requiring an lpr (Fas)
      product on target cells and a gld product on effector cells. Activated lymphocyte
      populations were also shown to contain F-CMC target cells. Activated lymphocyte
      populations thus contained both effector and target F-CMC cells, which could lyse
      each other. Fas-based cytotoxicity can thus lead to the lysis of syngeneic
      activated lymphocytes, consistent with the possibility of its participation in
      the down-regulation of immune responses, and more generally offering a model of
      socially controlled, direct membrane-mediated cell death.

PMID- 7512035
TI  - gld/gld mice are unable to express a functional ligand for Fas.
AB  - Mice homozygous for either the lpr or gld genes develop phenotypically identical
      autoimmune disorders. The gene responsible for the pathology in lpr/lpr mice
      encodes the Fas antigen, a protein associated with the induction of programmed
      cell death. To determine if the defect associated with gld represents a mutation
      in the ligand for Fas, we have assessed the ability of lymphoid cells from
      homozygous gld/gld mice to lyse target cells in a Fas-dependent manner. Using an
      antagonistic antibody to Fas, we demonstrate that activated T cells from normal
      and lpr mice are capable of inducing Fas-mediated lysis of tumor target cells. In
      contrast, activated T cells from gld/gld mice fail to induce lysis of tumor
      targets, although cells from gld mice are able to lyse specific allogeneic
      targets following mixed lymphocyte culture. In addition, activated T cells from
      gld/gld homozygous animals are not capable of binding to a Fas.Fc fusion protein
      at high levels, whereas activated T cells from normal and lpr/lpr animals bind
      Fas.Fc efficiently. These data indicate that mice homozygous for gld are unable
      to express a functional ligand for Fas.

PMID- 7512036
TI  - T cell receptor antagonist peptides are highly effective inhibitors of
      experimental allergic encephalomyelitis.
AB  - The feasibility of using T cell receptor (TcR) antagonist peptides to inhibit
      autoimmune disease has been examined. First, the fine antigenic structure of the
      I-As-restricted encephalitogenic determinant proteolipid protein (PLP) 139-151
      has been analyzed. It was found that residues 145 and 148 were I-As anchor
      residues, and residue 144 appeared to be especially critical in T cell
      activation. Residues 142, 143, 146, and 147 were found to be crucial for
      activation of some, but not all, of the T cells studied. Next, good I-As-binding
      nonantigenic analogs were tested for TcR antagonism. Accordingly, several single
      substitution analogs were identified which could act as TcR antagonists.
      Moreover, when two such analogs were combined, the resulting TcR antagonist pool
      inhibited most of the PLP 139-151-specific T cell clones in vitro. When the
      efficacy of this TcR antagonist pool in inhibiting EAE induction in vivo was
      examined, it was found that the analog pool was a remarkably potent inhibitor of
      disease induction. The TcR antagonist pool was approximately 10-fold more potent
      than our best major histocompatibility complex blocker and was still capable of
      significant inhibition when injected in equimolar amounts with the
      encephalitogenic PLP 139-151 determinant.

PMID- 7512037
TI  - Plastic-immobilized anti-mu or anti-delta antibodies induce apoptosis in mature
      murine B lymphocytes.
AB  - It is widely accepted that extensive cross-linking of surface immunoglobulin
      (sIg) receptors on mature B cells promotes their activation and progression
      through the cell cycle. A commonly employed method to maximize receptor cross
      linking via anti-receptor antibodies is to immobilize them on tissue culture
      plastic. We show here that immobilizing monoclonal anti-mu or anti-delta
      antibodies, which are mitogenic in solution, on plastic abrogates their capacity
      to induce DNA synthesis in mature murine B cells, even in the presence of
      interleukin-4 (IL-4). The cells do become abortively activated, as evidenced by
      up-regulation of major histocompatibility complex class II antigen levels, but
      subsequently virtually all of them die, manifesting DNA fragmentation
      characteristic of apoptosis. The induction of apoptosis is abrogated by the
      inclusion of either IL-4 or anti-CD40 antibodies in the cultures, with the two
      stimuli acting in concert. We believe that the system represents a polyclonal
      model of clonal deletion tolerance in mature B cells, such as may be induced
      under physiological conditions by antigens with repeating epitopes.

PMID- 7512038
TI  - Cyclopiazonic acid stimulates Ca2+ influx through non-specific cation channels in
      endothelial cells.
AB  - A non-specific cation channel in cultured human umbilical vein endothelial cells
      was obtained by cell-attached patch-clamp study. This channel showed a
      conductance of 28 pS when both pipette and bath contained 140 mM potassium
      chloride. when pipette solution was changed into 140 sodium chloride with 5 mM
      calcium chloride, the conductance was 26 pS. when 120 mM calcium chloride was
      used as the only cation in the pipette, a conductance of 6 pS was obtained. Bath
      application of cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum
      Ca2+ pump in smooth muscle and other tissues, dose dependently activates this non
      specific cation channel. It is assumed that cyclopiazonic acid by blockade of the
      refilling of Ca2+ stores depletes the rapidly exchanging intracellular Ca2+
      stores and this action stimulates Ca2+ influx through the non-specific cation
      channels in human umbilical vein endothelial cells.

PMID- 7512040
TI  - Relaxant mechanisms of cyclic AMP-increasing agents in porcine coronary artery.
AB  - We investigated the relaxant mechanisms of the cyclic AMP (cAMP)-increasing
      agents, isoproterenol, T-0509, forskolin and 3-isobutyl-1-methylxanthine (IBMX),
      on porcine coronary arteries contracted with U46619 (300 nM), a thromboxane A2
      analogue, or 30 mM KCl, by measuring force simultaneously with intracellular Ca2+
      concentration ([Ca2+]i) or cAMP and cyclic GMP (cGMP) levels. In U46619
      contracted arteries, these agents decreased [Ca2+]i and force of contraction to
      almost the same extent in a concentration-dependent manner, whereas in KCl
      contracted arteries these agents, except IBMX at higher concentrations, produced
      a relaxation with little change in [Ca2+]i. These agents all elevated tissue cAMP
      levels, and in addition, IBMX at higher concentrations increased cGMP levels. In
      Ca(2+)-free medium, these agents produced a concentration-dependent inhibition of
      Ca2+ release from intracellular Ca2+ stores induced by U46619 but not by 25 mM
      caffeine. Isoproterenol at a high concentration (3 microM) transiently decreased
      [Ca2+]i but steadily relaxed KCl-contracted arteries. This decrease in [Ca2+]i,
      but not the relaxation was inhibited by ryanodine and caffeine treatments. These
      results suggest that the relaxant mechanism of these agents on KCl-contracted
      arteries is mainly due to phosphorylation of myosin light chain kinase via cAMP
      dependent protein kinase, resulting in a reduction of the Ca2+ sensitivity of
      contractile elements. Their relaxant mechanism in U46619-contracted arteries
      seems due to the inhibition of signal transduction of the agonist, resulting in a
      decrease in [Ca2+]i and inhibition of the Ca2+ sensitization.

PMID- 7512039
TI  - Role of nitric oxide in the peristalsis in the isolated guinea-pig ileum.
AB  - The role of nitric oxide in peristalsis was studied by using NG-nitro-L-arginine,
      an inhibitor of the biosynthesis of nitric oxide, in the isolated guinea-pig
      ileum. Constant peristalsis was cyclically induced by distending the ileal wall
      with intraluminal solution infused at a constant rate. NG-Nitro-L-arginine (10(
      6) to 10(-4) M) dose dependently increased the frequency of peristalsis. This
      effect of NG-nitro-L-arginine was almost hindered by pretreating the ileum with
      10(-3) M L-arginine, but not D-arginine. Nitroprusside (5 X 10(-7) M) reversed
      the frequency increase. In the presence of NG-nitro-L-arginine, peristaltic
      propulsion occurred at a smaller distension of the ileal wall and the ileum
      constricted to a smaller diameter at the completion of propulsion. The rate of
      shortening of longitudinal muscle during distension was raised by NG-nitro-L
      arginine, although the peak magnitudes were not changed. Consistent with these
      effects of NG-nitro-L-arginine on peristalsis, NG-nitro-L-arginine at 10(-5) M
      increased the contractions of circular muscle in response to electrical field
      stimulation, but not those of longitudinal muscle. These results suggest that
      endogenous nitric oxide modulates peristalsis by limiting the contractile
      activity of the circular muscle of the guinea-pig ileum.

PMID- 7512041
TI  - Suppression of angiogenesis by the antitumor agent titanocene dichloride.
AB  - Titanocene dichloride, which is an active antitumor agent against solid but not
      blood-borne tumors, suppresses angiogenesis and inhibits biosynthesis of
      collagenous proteins in the in vivo system of the chorioallantoic membrane of the
      chick embryo. The agent does not affect total protein biosynthesis in the same
      system. At non-toxic dose regimens titanocene dichloride retards the growth of
      Walker 256 carcinosarcoma transplants in rats and reduces the number of seeded
      implants in the mesenteric bed. At concentrations which suppress angiogenesis and
      inhibit biosynthesis of collagenous proteins, the agent does not affect the
      viability of Walker 256 carcinosarcoma cells, or the attachment and proliferation
      of human A549 lung adenocarcinoma or human umbilical vein endothelial cells in
      culture. It appears that the antitumor activity of titanocene dichloride may be
      attributed, at least in part, to its ability to suppress angiogenesis.

PMID- 7512042
TI  - Induction of nitric oxide synthase in human mammary arteries in vitro.
AB  - This study investigated whether human mammary arteries express an inducible
      nitric oxide (NO) synthase and, if so, what its effects are on vascular tone. In
      human mammary artery pre-contracted with phenylephrine there was a gradual time
      dependent loss of tone over an 8 h period. L-Arginine and lipopolysaccharide
      enhanced the rate but not the magnitude of this loss in tone, whereas NG-nitro-L
      arginine, NG-monomethyl-L-arginine, dexamethasone, and polymyxin B inhibited
      these effects. These findings indicate that incubation of human mammary artery
      with lipopolysaccharide resulted in the expression of an inducible NO synthase.
      The induction of this enzyme in human vessels may be important in the
      pathogenesis of septic shock.

PMID- 7512043
TI  - Effects of dicentrine, a novel alpha 1-adrenoceptor antagonist, on human
      hyperplastic prostates.
AB  - The effects of dicentrine, an alpha 1-adrenoceptor antagonist, on human
      hyperplastic prostates were investigated by radioligand binding and in vitro
      isometric tension experiments. In human hyperplastic prostates, alpha 1
      adrenoceptors were characterized by a binding assay using [3H]prazosin as a
      radioligand. Specific [3H]prazosin binding was saturable and of high affinity (Kd
      = 0.2 +/- 0.02 nM) with a maximal number of binding sites (Bmax = 55.2 +/- 3.2
      fmol/mg protein). alpha-Adrenoceptor antagonists competed with [3H]prazosin for
      binding in the order: dicentrine > phentolamine > rauwolscine. Norepinephrine
      (0.3-100 microM) or phenylephrine (1-300 microM) produced gradual contractions of
      human hyperplastic prostates. The concentration-response curve of norepinephrine
      or phenylephrine was shifted in parallel to the right by dicentrine, consistent
      with a competitive blockade. The pA2 values of dicentrine against norepinephrine
      and phenylephrine were 8.04 +/- 0.09 and 8.33 +/- 0.11, respectively. These
      experiments were conducted to confirm that there was no interaction between alpha
      1- and alpha 2-adrenoceptors in the tissue. Rauwolscine (1 microM) caused 1.7
      fold, while dicentrine (0.1 microM) caused 15.8-fold shift of norepinephrine
      induced contraction of human hyperplastic prostates. Combination of rauwolscine
      with dicentrine caused 17.8-fold shift of norepinephrine-induced prostatic tissue
      contraction. The contractile response to transmural field stimulation was
      abolished by pretreatment with tetrodotoxin, and suppressed concentration
      dependently by dicentrine or prazosin, whereas rauwolscine had little effect. It
      is concluded that dicentrine inhibits human hyperplastic prostate contractions in
      response to exogenous and endogenous adrenergic stimulation. Dicentrine may thus
      hold potential to relieve bladder outlet obstruction caused by benign prostatic
      hyperplasia via alpha 1-adrenoceptor blockade.

PMID- 7512044
TI  - Ribotyping as an epidemiologic tool for Escherichia coli.
AB  - Restriction fragment length polymorphism of ribosomal RNA genes was analysed
      among 133 Escherichia coli strains predominantly from blood and urine, including
      21 isolates from faeces of healthy persons. The strains had also been
      characterized for their O:K:H serotypes, for the presence of P, S and type 1C
      fimbriae, non-P, non-S mannose-resistant haemagglutinins and haemolysin
      production. Hind III-digested genomic DNA was subjected to Southern blot analysis
      with either plasmid pKK3535 containing E. coli rRNA operon or purified rRNA as a
      probe. Among the 133 strains 20 ribotypes were obtained. The distribution of
      strains into different ribotypes generally correlated with their O:K:H serotype.
      Ribotype variation within serotypes was mainly seen among strains with the K5
      capsule. The origin of the strains or the presence of virulence-associated
      factors did not correlate with the ribotype. In conclusion, ribotyping appears to
      be a valuable method in epidemiologic studies especially when the serotyping
      methods are not available.

PMID- 7512046
TI  - Amelioration of azidothymidine-induced erythroid toxicity by hemin and stem cell
      factor in immune-suppressed mice.
AB  - Recombinant cytokines such as stem cell factor (SCF) are currently being tested
      for the ability to ameliorate 3'azido-3'deoxythymidine (AZT)-induced anemia in
      AIDS patients. Recently, we showed that SCF greatly increased burst-forming units
      erythroid (BFU-E) but failed to increase hematocrits of AZT-treated immune
      deficient (MAIDS) mice. We reasoned that hemin, previously shown to both enhance
      BFU-E proliferation and accelerate erythroid maturation, might bring about
      differentiation of this large SCF-induced pool of BFU-E and further protect BFU-E
      from AZT's toxic effect. We therefore studied, in vitro, the effect of
      combinations of hemin and SCF on growth of BFU-E from MAIDS mice. Hemin, at
      concentrations of 10 to 100 microM, ameliorated the growth-inhibitory effect of
      AZT. 50 microM hemin increased the ED50 of AZT from 1 x 10(-7) M to 1.7 x 10(-6)
      M. SCF also ameliorated AZT-induced toxicity, but to a lesser extent. SCF and
      hemin increased the number of BFU-E colonies observed in the presence of AZT in
      an additive fashion. The resistance of BFU-E to AZT's cytotoxic effect was
      greater in cultures receiving hemin and SCF together than in cultures receiving
      SCF or hemin alone. Zinc and tin protoporphyrins (Zn and Sn PP) increased the
      numbers of BFU-E observed. However, neither zinc nor tin protoporphyrins
      increased the ED50 of AZT. Combinations of SCF and hemin may prove useful in
      ameliorating AZT toxicity in both immune-suppressed mice and human
      immunodeficiency virus (HIV)-infected patients.

PMID- 7512047
TI  - Effects of recombinant human Steel factor (c-kit ligand) on early cord blood
      hematopoietic precursors.
AB  - The purpose of this study was to define the effects of recombinant human Steel
      factor (rhSF) (c-kit ligand) on early and late cord blood hematopoietic
      progenitors. In the presence of recombinant human erythropoietin (rhEpo), rhSF
      supported the development of granulocyte/macrophage, erythroid, and mixed
      colonies from CD34-positive cord blood cells. With increasing concentrations of
      rhSF, an increase in the number of mixed colonies was observed. This increase was
      paralleled by a decrease in the number of erythroid colonies, such that the total
      number of the two colony types was always constant. Similar results were observed
      when CD34+ cells were cultured in the presence of a combination of rhEpo, rhSF,
      and rhIL-3. These results indicate that the presence of rhSF enhanced the
      detectability of the nonerythroid components of mixed colonies. The effect of
      rhSF on early progenitors (pre-colony-forming units [pre-CFU]) was studied in a
      two-step assay. In this assay, cells positive for CD34 and resistant to treatment
      with 4-hydroperoxycyclophosphamide (CD34+/4-HCres) were cultured in suspension
      for 7 days with rhSF, rhIL-3, or rhSF plus rhIL-3 and then plated in clonogenic
      assays. Before suspension culture, CD34+/4-HCres cells had a low clonogenic
      potential (0.37%). After being cultured in suspension, however, these cells gave
      rise to a large number of colonies of all types when replated. Cells cultured in
      suspension with the combination of rhSF and rhIL-3 increased significantly in
      number and gave rise to more colonies, when compared to cells cultured with
      either factor alone (synergistic effect). In identical experiments, such as
      effect had not been observed with combinations of rhIL-3 and either rhIL-1 or
      rhIL-6. Thus, rhSF supports the expansion and differentiation of early
      progenitors in human cord blood.

PMID- 7512045
TI  - The effect of angiostatic steroids and beta-cyclodextrin tetradecasulfate on
      corneal neovascularization in the rat.
AB  - Folkman and coworkers have described angiostatic steroids that markedly inhibit
      neovascularization of the rabbit cornea when given topically with beta
      cyclodextrin tetradecasulfate (beta-CD), yet have minimal or no glucocorticoid or
      mineralocorticoid activity. Our objective was to extend these observations to
      another species, the rat. We induced neovascularization by cauterizing rat
      corneas with silver nitrate/potassium nitrate; drugs were applied topically four
      times per day for 4 days in most experiments. Submicron sized emulsions of lipid
      soluble dexamethasone and the angiostatic steroids 17 alpha-hydroxyprogesterone
      (1 or 10 mg ml-1) and cortexolone (1 or 10 mg ml-1) were prepared by lecithin
      encapsulation of drug microcrystals. The vehicle for water-soluble hydrocortisone
      21-phosphate (HCP) +/- beta-CD (Molecusol; Pharmatec, Inc) was 10% Tween 20 in
      Tris-buffered 0.9% saline. Angiogenesis was significantly inhibited only by 1 mg
      ml-1 dexamethasone (-63.2% when compared with controls), 0.5 mg ml-1 HCP + 1 mg
      ml-1 beta-CD (-33.4%), and 1 mg ml-1 HCP (-40.2%). HCP (0.5 mg ml-1) or beta-CD
      (1 or 2 mg ml-1) alone had no significant effect on neovascularization; the
      inhibition by 1.0 mg ml-1 HCP was not potentiated by 2 mg ml-1 beta-CD. We also
      tested HCP and tetrahydro-S (TH-S) using 1.5% hydroxypropyl methylcellulose
      vehicle and beta-CD from Takeda Chemical Industries, Ltd., to simulate the
      procedure of Folkman and coworkers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512048
TI  - Flow-cytometric analysis of in vivo induction of differentiation of WEHI-3B
      myelomonocytic leukemia cells by recombinant granulocyte colony-stimulating
      factor.
AB  - An animal leukemia model was developed to investigate in vivo induction of
      differentiation of myeloid leukemia cells. An aneuploid cell line (C15) was
      isolated from mouse myelomonocytic leukemia WEHI-3B D+ cells. The C15 cells
      contained twice as much DNA as the parental cells but retained the morphology of
      myelomonocytic cells and the ability to differentiate into macrophage-like cells
      in response to all-trans retinoic acid (ATRA) in vitro. When the C15 cells were
      inoculated into the peritoneal cavity of syngeneic Balb/c mice (10(6)
      cells/mouse), the mice died of leukemia within 19 days. The DNA content and
      differentiation antigen (Mac-1) of the cells in the peritoneal cavity were
      determined by dual-parameter flow cytometry. On day 12 after inoculation, the C15
      cells were distinguishable from normal host cells in the peritoneal cavity by
      their different DNA content. The administration of recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) (10 micrograms/day) to mice bearing C15 cells
      induced the leukemia cells to express Mac-1 antigen and to change morphologically
      into mature granulocytic cells. Because the C15 cells were not responsive to G
      CSF in suspension culture in vitro, this result suggests that the cytokine's
      actions on the cells in vivo and in vitro are different. This experimental model
      for analyzing in vivo differentiation of leukemia cells will be useful for
      studying the therapeutic effects of potential differentiation-inducing agents.

PMID- 7512049
TI  - A comparison of magnification functions in area 19 and the lateral suprasylvian
      visual area in the cat.
AB  - A retinotopic map can be described by a magnification function that relates
      magnification factor to visual field eccentricity. Magnification factor for
      primary visual cortex (V1) in both the cat and the macaque monkey is directly
      proportional to retinal ganglion cell density. However, among those extrastriate
      areas for which a magnification function has been described, this is often not
      the case. Deviations from the pattern established in V1 are of considerable
      interest because they may provide insight into an extrastriate area's role in
      visual processing. The present study explored the magnification function for the
      lateral suprasylvian area (LS) in the cat. Because of its complex retinotopic
      organization, magnification was calculated indirectly using the known
      magnification function for area 19. Small tracer injections were made in area 17,
      and the extent of anterograde label in LS and in area 19 was measured. Using the
      ratio of cortical area labeled in LS to that in area 19, and the known
      magnification factor for area 19 at the corresponding retinotopic location, we
      were able to calculate magnification factor for LS. We found that the
      magnification function for LS differed substantially from that for area 19:
      central visual field was expanded, and peripheral field compressed in LS compared
      with area 19. Additionally, we found that the lower vertical meridian's
      representation was compressed relative to that of the horizontal meridian. We
      also examined receptive field size in areas 17, 19, and LS and found that, for
      all three areas, receptive field size was inversely proportional to magnification
      factor.

PMID- 7512050
TI  - Cortical networks for visual reaching.
AB  - The cortical anatomical substrates by which visual information may influence the
      frontal areas controlling reaching movements to visual targets were studied in
      monkeys. A reaching task was employed to characterize the arm-related regions of
      the frontal lobe. Injections of retrograde tracers into these physiologically
      defined cortical fields revealed a gradient of parallel corticocortical pathways
      originating in the superior parietal lobule and impinging upon different frontal
      regions. These results support the hypothesis that the superior parietal lobule
      can supply the frontal motor and premotor areas not only with the proprioceptive
      information but also with the visual input required for the control of reaching.

PMID- 7512051
TI  - Prevalence of antibodies to hepatitis C virus among family members of patients
      with chronic hepatitis C.
AB  - In this study, 108 family members of 40 chronically HCV-infected patients (19
      post-transfusion and 21 sporadic), and 45 families of 16 anti-HCV-negative index
      cases (control group) were tested for anti-HCV antibodies. Anti-HCV antibodies
      were found in 16 (14.8%) families of anti-HCV-positive index cases (15% males and
      14.6% females; p = NS), with no difference between families of index cases with
      post-transfusion and those with sporadic HCV infection. Out of the 16 anti-HCV
      positive family members, 12 (75%) had clinical and/or serological evidence of
      chronic liver damage. None of the control group subjects were anti-HCV-positive
      (p < 0.01). The rate of anti-HCV positivity was 34.4% among spouses, 14.3% among
      siblings, 16.7% among cohabitants and 2.3% among children; anti-HCV antibodies
      were not detected among parents. We found a positive correlation between the
      prevalence of anti-HCV antibodies among families and the severity of the HCV
      related chronic liver damage of the index cases (p < 0.00005). In addition, to
      confirm that HCV infection and HCV-related chronic hepatitis may be transmitted
      intrafamiliarly, our findings also indicate that horizontal, especially sexual
      contact, is a more important route of HCV infection than vertical/perinatal
      transmission. Finally, the risk of acquiring HCV infection among families appears
      to be the highest when index cases are suffering from severe HCV-related chronic
      hepatitis.

PMID- 7512052
TI  - Low prevalence of anti-HCV antibodies in hospital workers.

PMID- 7512054
TI  - High continuing pregnancy rates after in vitro fertilization-embryo transfer
      using medium supplemented with a plasma protein fraction containing alpha- and
      beta-globulins.
AB  - OBJECTIVE: To evaluate both the laboratory and clinical outcomes after IVF-ET
      using culture media supplemented with a plasma protein fraction (PPF, Plasmatein;
      Alpha Therapeutics, Los Angeles, CA) containing albumin and significant amounts
      of alpha- and beta-globulins. DESIGN: One-year clinical trial of a PPF with high
      globulin content as a medium supplement during IVF, embryo growth, and ET.
      SETTING: Fertility Center of San Antonio, a private, office-based center for
      assisted reproduction. PATIENTS: Ninety-eight couples, with women ranging in age
      from 26 to 46 years, undergoing 103 ovum retrievals for IVF-ET as treatment for
      infertility because of tubal factor, endometriosis, anovulation, uterine or
      cervical factor, male factor, and unexplained causes. MAIN OUTCOME MEASURES:
      Fertilization rate, zygote cleavage rate, clinical pregnancy rate (PR),
      continuing PRs, and implantation rates. RESULTS: Supplementation with PPF in
      insemination, growth and transfer medium resulted in a clinical PR of 41.5% per
      transfer with continuing PRs of 35.2% per retrieval, 37.2% per patient, and 38.7%
      per transfer. CONCLUSIONS: A PPF containing significant amounts of alpha- and
      beta-globulins can serve as an effective protein supplement to IVF medium, with
      outcomes manifested as high continuing PRs. These data indicate a potential role
      for glycoprotein components of serum in supporting healthy embryo growth in
      vitro, although the mechanism may relate more to the general physicochemical
      properties of this fraction than to the actions of a specific component.

PMID- 7512056
TI  - Leukemia inhibitory factor and nerve growth factor are retrogradely transported
      and processed by cultured rat sympathetic neurons.
AB  - How neurons convert the presence of factors at their axon terminals into signals
      that affect mechanisms in their cell bodies is unknown, but retrograde axonal
      transport of the factors themselves may be involved. Nerve growth factor (NGF)
      and leukemia inhibitory factor (LIF) have previously been shown to produce
      changes in cell bodies of sympathetic neurons when applied to their peripheral
      neurites, and it is well established that NGF is retrogradely transported along
      sympathetic axons. In this study we show that 125I-LIF applied to terminal
      neurites of rat sympathetic neurons in compartmented cultures is retrogradely
      transported, but at a much lower level compared to the retrograde transport of
      125I-NGF. Transport of 125I-LIF was competed by cotreatment with unlabeled LIF
      and was blocked by cotreatment with dinitrophenol. The rate of 125I-LIF transport
      was independent of NGF concentration. However, both 125I-LIF and 125I-NGF
      transport was reduced by pretreating neurons with LIF. SDS-PAGE analysis showed
      that retrogradely transported radiolabel which accumulated in cell body
      containing extracts following transport of both 125I-LIF and 125I-NGF consisted
      of intact as well as partially processed species. Radiolabel also accumulated in
      the medium bathing the cell bodies and migrated near the dye front on SDS-PAGE,
      implying that both factors were extensively degraded and released by the neurons.
      These results are consistent with the suggestion that the retrograde transport of
      LIF, as thought for NGF, may be important for retrograde signaling mechanisms.

PMID- 7512055
TI  - Novel human endometrial cell line promotes blastocyst development.
AB  - OBJECTIVE: To test and contrast the embryotrophic potential of an established
      human endometrial cell line to that of two other epithelial cell types: human
      oviduct and African monkey kidney (Vero) cells. DESIGN: Mouse IVF was performed.
      Subsequent development of embryos cocultured with our endometrial cell line was
      contrasted to that seen with oviductal and Vero cell coculture systems. Percent
      blastocyst transformation, expansion, and hatching were compared. SETTING:
      University-based research laboratory associated with clinical IVF program.
      RESULTS: All three epithelial cell monolayers tested significantly improved the
      rate of blastocyst transformation of in vitro fertilized murine oocytes. The
      overall percent blastocysts obtained was highest with endometrial cells (69%),
      followed by oviductal cells (52%), Vero cells (45%), and the medium-alone
      controls (29%). Only 13% of oviduct cocultured embryos were able to reach the
      hatched blastocyst stage compared with a 30% hatching rate with endometrial cells
      and a 21% hatching rate with Vero cells. Only 3% of control embryos hatched in
      vitro. CONCLUSION: We have described a novel continuous endometrial cell line
      with excellent embryotrophic potential. This cell line is technically easy to use
      and is of human origin. As a coculture system it appears to be superior to both
      oviductal and Vero cells in correcting for defects in culture environment during
      in vitro development up to the blastocyst stage.

PMID- 7512053
TI  - Analysis of 369 abortions conducted by mifepristone (RU486) associated with
      sulprostone in a French family planning center.
AB  - OBJECTIVE: To investigate the use of oral mifepristone (RU486; Roussel-Uclaf,
      Paris, France) associated with IM injection of sulprostone (Schering, Lys-Lez
      Lannoy, France) for the induction of legal abortion (7 weeks of amenorrhea in
      France). DESIGN: An uncontrolled observational study. SETTING: A public family
      planning center in Paris. PATIENTS: Three hundred sixty-nine (369) pregnant women
      with up to 7 weeks amenorrhea undergoing legal abortion. INTERVENTIONS: Six
      hundred milligrams (600 mg) of oral mifepristone followed 48 hours later by an IM
      injection of 250 micrograms of sulprostone. MAIN OUTCOME MEASURES: Frequency of
      complete abortion and the need for subsequent surgical evacuation,
      hospitalization, and blood transfusion. Measurement of the beta-hCG concentration
      before and 14 days after the oral administration of mifepristone. RESULTS: There
      was complete abortion in 93.2% of the cases. Of the 25 failures, 8 were continued
      pregnancies, 6 terminated pregnancy but without expulsion of the conceptus, and
      11 were placenta retentions. Eight women required short hospitalization, but none
      needed blood transfusion. Among the 25 failures, 23 had a beta-hCG concentration
      > 500 IU/mL [sensitivity 92%, specificity 83%]. CONCLUSION: The sequential use of
      oral mifepristone and IM injection of sulprostone is effective in inducing
      abortion up to 7 weeks of amenorrhea. Nevertheless the risk of maternal morbidity
      associated with sulprostone and also the risk of fetal malformations in cases of
      continued pregnancy indicate that this method should only be used in specialist
      centers.

PMID- 7512057
TI  - Sperm-surface chymotrypsin-like protease activity required for fertilization in
      ascidians.
AB  - During fertilization, species-specific gamete binding must be followed by sperm
      penetration of egg vestments before gamete fusion can occur. Sperm proteases,
      called lysins, aid this process. Sperm from Ascidia ceratodes, Ascidia callosa,
      and Ascidia paratropa were found to have a surface-mounted chymotrypsin-like
      protease when studied by enzymology, biotinylated, immunolabeling, and
      histochemistry. Chymotrypsin substrates and inhibitors blocked fertilization in a
      concentration-dependent manner in A. ceratodes and decreased the number of sperm
      heads which penetrated the egg's vitelline coat, but had no effect on sperm
      binding to follicle cells. Sperm bound to agarose beads coated with the
      chymotrypsin inhibitor alpha 2-macroglobulin. Chymotrypsin-like enzyme activity,
      assayed fluorimetrically using N-succinyl-leucinyl-leucinyl-valinyl-tyrosinyl-7 
      amido-4-methyl-coumarin as the substrate, was associated with head fractions
      prepared by differential centrifugation. Biotinylation of live sperm followed by
      detergent extraction showed that chymotrypsin-like activity could be removed from
      the detergent extract using avidin-agarose beads. Indirect immunofluorescence of
      unreacted and reacted sperm heavily labeled membrane domains overlying the
      mitochondrion and at the base of the head with occasional labeling of the sperm
      tip. Histochemical studies, which used N-succinyl-alanyl-alanyl-prolyl
      phenylalanyl-beta-naphthylamide as the substrate, colocalized enzyme activity in
      head regions of unreacted and near the mitochondrion of reacted sperm. Thus, we
      conclude that in ascidian sperm a chymotrypsin-like protease is exposed on the
      external surface of the plasma membrane of the head, is required for
      fertilization, and plays a role in sperm penetration but not binding.

PMID- 7512058
TI  - Interstitial collagenase is required for angiogenesis in vitro.
AB  - Human umbilical vein endothelial cells (HUVECs) invade collagen gels and
      establish vascular-like structures within the gel following stimulation with
      phorbol esters. This process was quantitated by measuring release of
      radioactivity from gels composed of [3H]collagen. Collagen was steadily degraded
      over the period of several weeks by phorbol ester-treated cells while little
      collagenolysis by cells not receiving phorbol ester was noted. Examination of
      matrix metalloproteinases (MMPs) secreted by HUVECs revealed a prominent
      induction of interstitial collagenase. Production of the mature forms of
      gelatinase A was also stimulated, as was the secretion of gelatinase B.
      Stromelysin was not detected. Two inhibitors of MMPs, the naturally occurring
      tissue inhibitor of metalloproteinases (TIMP; 10 micrograms/ml) and the
      synthetic, peptide inhibitor BB-94 (1 microM) were both effective at blocking
      HUVEC-mediated collagen degradation. Morphological examination of control, PMA
      treated HUVECs, as well as PMA-treated HUVECs receiving TIMP or BB-94, revealed
      that MMP inhibition resulted in a block to invasion and tubule formation within
      the collagen gels. Similar results for MMP expression and inhibition of tubule
      formation in vitro were obtained with human dermal microvascular endothelial
      cells. Examination of collagen proteolytic fragments revealed that both BB-94 and
      TIMP blocked cleavage of the alpha 1 and alpha 2 chains of type I collagen and
      the appearance of tropocollagen fragments A and B, demonstrating that the
      inhibitors were acting directly upon interstitial collagenase. Our results
      demonstrate that interstitial collagenase is required for angiogenesis in vitro.

PMID- 7512059
TI  - Effect of nutrients, hormones and serum on survival of rat islet beta cells in
      culture.
AB  - This study quantifies the survival of purified single rat beta cells under
      different culture conditions. Less than 10% of the cells survive 9 days of
      culture in Ham's F10 medium without supplements. Addition of fetal calf serum
      (5%) increases cell survival to 54% in the absence and to 78% in the presence of
      isobutylmethylxanthine (50 mumol/I). The effect of serum is explained, at least
      partly, by the presence of albumin and of low molecular weight constituents. In
      serum-free Ham's F10 with 50 mumol/l isobutylmethylxanthine, 75% of cells survive
      after the addition of bovine serum albumin (1%) and of ultroser (0.2%), a
      commercial serum substitute. Survival of at least 75% of cells is also maintained
      in Ham's F10 with isobutylmethylxanthine plus albumin, and supplemented by
      metabolizable nutrients or by the peptides glucagon (10(-8) mol/l) or growth
      hormone (1 micrograms/ml) plus insulin like growth factor-I (50 ng/ml). D-Glucose
      increases beta-cell survival in a dose-dependent manner up to 10 mmol/l; a
      beneficial effect is also observed with other metabolizable compounds (leucine
      and glutamine) but not with non-metabolizable monosaccharides. Glucose-induced
      survival of islet beta cells can be attributed to its dose-dependent recruitment
      of cells into metabolic activities; however, a 9-day exposure to excessively high
      nutrient concentrations (> 20 mmol/l glucose) is deleterious to the cells. These
      results define culture media, with or without serum, wherein at least 75% of
      single rat islet beta cells can survive for a minimum of 9 days. This will allow
      for studies on beta-cell toxic conditions and potentially protective
      agents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512061
TI  - Evaluation of a new cytotoxicity assay for Clostridium perfringens type D epsilon
      toxin.
AB  - A new cytotoxicity assay for determining the activity of epsilon toxin produced
      by Clostridium perfringens type D has been developed. Viability of cultured cells
      was determined by the ability of only live cells to convert 5-(3
      carboxymethoxyphenyl)-2-(4,5-dimethylthiazolyl)-3-(4- sulfophenyl)tetrazolium to
      the coloured product formazan in the presence of phenazine methosulfate. Of the
      12 cell lines tested, only the MDCK cell line was susceptible to epsilon toxin.
      Specificity was confirmed by the ability of only specific monoclonal antibodies
      to inhibit cytotoxicity. Good correlation was obtained with the mouse lethality
      assay (r = 0.991) and over a wide range of viability (15-75%) as determined by
      ethidium bromide/acridine orange staining (r = 0.995).

PMID- 7512060
TI  - Expression of glycogen synthase and phosphofructokinase in muscle from type 1
      (insulin-dependent) diabetic patients before and after intensive insulin
      treatment.
AB  - The aim of the present study was to determine whether short-term appropriate
      insulinization of Type 1 (insulin-dependent) diabetic patients in long-term poor
      glycaemic control (HbA1C > 9.5%) was associated with an adaptive regulation of
      the activity and gene expression of key proteins in muscle glycogen storage and
      glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine
      diabetic patients biopsies of quadriceps muscle were taken before and 24-h after
      intensified insulin therapy and compared to findings in eight control subjects.
      Subcutaneous injections of rapid acting insulin were given at 3-h intervals to
      improve glycaemic control in diabetic patients (fasting plasma glucose decreased
      from 20.8 +/- 0.8 to 8.7 +/- 0.8 mmol/l whereas fasting serum insulin increased
      from 59 +/- 8 to 173 +/- 3 pmol/l). Before intensified insulin therapy, analysis
      of muscle biopsies from diabetic patients showed a normal total glycogen synthase
      activity but a 48% decrease (p = 0.006) in glycogen synthase fractional velocity
      (0.1 mmol/l glucose 6-phosphate) (FV0.1) and a 45% increase (p = 0.01) in the
      half-maximal activation constant of glycogen synthase (A0.5). The activity of
      phosphofructokinase and the specific mRNA and immunoreactive protein levels of
      both glycogen synthase and phosphofructokinase were similar in the two groups.
      The 2.8-fold increase in serum insulin levels and the halving of the plasma
      glucose level for at least 15 h were associated with a normalization of glycogen
      synthase fractional activity (FV0.1) and of the half-maximal activation constant
      (A0.5) whereas the enzyme activity of phosphofructokinase and the mRNA and
      protein levels of both glycogen synthase and phosphofructokinase remained
      normal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512062
TI  - Palliation of malignant dysphagia by ethanol induced tumour necrosis.
AB  - Thirty two patients (74 (43-93) years; median, (range)) with dysphagia because of
      inoperable, unresectable or recurrent oesophagogastric carcinoma were treated by
      ethanol induced tumour necrosis (ETN). Endoscopic injection of absolute alcohol
      was performed using a variceal injector needle, with 0.5-1 ml aliquots injected
      retrogradely from distal to proximal tumour margin. Dilatation to 12 mm was used
      only if the endoscope would not traverse the stricture. In patients with total
      occlusion, injection into the proximal tumour was followed by a repeat endoscopy
      3-7 days later. Dysphagia was graded from 0 = no dysphagia to 4 = total
      dysphagia. The significance of changes in the dysphagia grade after ETN were
      assessed using the Wilcoxon rank sum test. Results (median (range)) were as
      follows: stricture length = 5.0 cm (1-15). Dysphagia grade before treatment was 3
      (2-4) improving after first treatment to 1 (0-3), p < 0.003. Best dysphagia grade
      achieved was 1 (0-3) and interval between treatments was 28.5 days (4-170). The
      volume of ethanol injected = 10 ml (1.5-29) and survival after first treatment
      was 93 days (6-660). The number of treatment sessions required to achieve best
      grade = 1 (1-3). There were no treatment complications. ETN significantly
      improves dysphagia. Results of palliation are similar to those of laser therapy,
      but can be achieved quickly and safely on a day case basis in most patients and
      at a small proportion of the cost.

PMID- 7512064
TI  - Ki67 and AgNORs staining in squamous cell carcinoma of the cervix: a comparison.
AB  - Ki67 immunostaining was performed on 48 cases of squamous cell carcinoma of the
      cervix and AgNOR silver staining on 29 cases. There was no correlation between
      the clinical stage of the tumor and the two methods of staining but both methods
      correlated with histological grade. There was no correlation between the two
      methods of staining in 17 case where they were done on adjacent blocks of tumor
      tissue. High Ki67 score but not high AgNOR count was significantly associated
      with early recurrence.

PMID- 7512063
TI  - Origin and development of exocrine pancreatic insufficiency in experimental renal
      failure.
AB  - Chronic renal failure affects the physiological function of many organ systems.
      One of them is the exocrine pancreas. Although varying degrees of pancreatic
      insufficiency are the dominating clinical characteristic of uraemic pancreatic
      disease, it remains unclear whether this disease should be regarded as a
      manifestation of chronic pancreatitis, arising from recurring attacks of acute
      pancreatitis, or represents a distinct entity. The exocrine pancreas was studied
      in a model of experimental renal failure. The pancreas was removed from each rat
      at selected time points over eight weeks after subtotal nephrectomy and from a
      standard rat model of pancreatitis for comparison. The data show that the in
      vitro secretory response is considerably changed in renal failure (increased
      during early acute and decreased during chronic renal failure). While the
      pancreatic content of digestive enzymes progressively declines, DNA and protein
      synthesis increase over time. Acinar cell deletion is increased and accompanied
      by an increased rate of mitosis. This increased cellular turnover is not
      associated with tissue oedema, pancreatic fibrosis, inflammatory changes,
      autophagocytosis or subcellular redistribution of lysosomal hydrolases, all of
      which are characteristic for pancreatitis. The ultrastructural changes of uraemic
      pancreatic disease bear no resemblance to the changes seen in pancreatitis. It is
      concluded that the morphological and biochemical changes in early uraemic
      pancreatic disease are quite distinct, correspond with toxic damage of the
      pancreas, and are dominated by functional impairment and an increased cellular
      turnover.

PMID- 7512066
TI  - [Clodronate in treatment of tumor osteopathy. Evaluation in tumor patients with
      bone metastases or hypercalcemia].
AB  - METHOD: In an observational study involving 398 tumor patients with bone
      metastases or related hypercalcemia, the effect of treatment with clodronate over
      a period of 12 months was investigated. Bone pain, analgesic requirements,
      quality of life and laboratory parameters were recorded at monthly intervals.
      RESULTS: Some 71.4% of all patients indicated an improvement in quality of life.
      Bone pain, experienced by 91.4% of the patients at the start of treatment,
      regressed (from 2.0 +/- 1.2 to 1.3 +/- 1.0). After the 12-month treatment period,
      36% of the patients did without analgesics completely (prior to treatment the
      corresponding figure was 24%). The most common side effects attributed to
      clodronate were gastrointestinal disorders (10%). CONCLUSION: Clodronate would
      appear to be a useful supportive drug in the management of tumor-related bone
      disease.

PMID- 7512067
TI  - [Expression of DNA fragment encoding for immunodominant epitopes of 150kd
      phosphoprotein of human cytomegalovirus in Escherichia coli].
AB  - HVYP fragment, which contains the DNA encoding region for immunodominant epitopes
      of 150 kd phosphoprotein (pp150) of human cytomegalovirus, was isolated from
      recombinant plasmid pHCY1 and the inserted into the PstI site of E. coli
      expression vector pUC8. The resulted recombinant plasmid pUHVYP1 with correct
      orientation and in-frame was transformed into E. coli JM107. Induced by isopropyl
      beta-D-thiogalactoside (IPTG), the transformants produced HVYP fusion protein
      with molecular weight of about 44-45 kd, as determined by 12% SDS-PAGE. These
      results from Western blot and ELISA showed that the expressed protein could be
      recognized by the specific anti-HCMV IgG and IgM antibodies of patients' serum.
      MAC-ELISA further proved that the fusion protein was a potential antigen for
      diagnostic reagents.

PMID- 7512065
TI  - Immunochemical properties of Vibrio cholerae LPS.
AB  - Immunochemical analysis of LPS isolated from Vibrio cholerae O1 and non O1 showed
      that this macromolecular complex shares common antigenic epitopes in the sugar
      moiety. The epitopes can be detected after mild alkaline hydrolysis of LPS in
      vitro. Membrane-associating activity of both O1 and non O1 LPS did not indicate
      any differences of the species.

PMID- 7512069
TI  - [Mutagenicity study of eight diesel emission samples].
AB  - Mutagenicity of eight diesel emission samples were examined by the
      Microsuspension test. The results showed that four samples were positive, and the
      others were negative. We also compared the method with the standard Ames test.
      The data showed that the microsuspension test is sensitive and economical. The
      microsuspension test method is useful for determining mutagenicity of
      environmental mutagens.

PMID- 7512068
TI  - [The influence of prostate-specific antigen p30 on human fertility].
AB  - The influence of prostate-specific antigen p30 on human fertility was studied
      with purified p30, domestic anti-p30 monoclonal and polyclonal antibodies. The
      results showed that the anti-p30 antibody presented in human serum had no
      negative effect upon human fertility and the anti-p30 antibody produced by
      heteroimmunization did not interfere with the process of human fertility in
      vitro. All these imply that it is unsuitable to recommend p30 as a contraceptive
      vaccine antigen.

PMID- 7512070
TI  - Simultaneous visualization of Helicobacter pylori and gastric morphology: a new
      stain.
AB  - Although the histopathologic patterns associated with Helicobacter pylori
      infection have been described, details of the interaction between bacteria,
      epithelial cells, and inflammatory cells remain elusive. One of the limiting
      factors has been the lack of a staining technique that allows the simultaneous
      visualization of H pylori and tissue morphology. By combining three commonly
      available stains (Steiner, hematoxylin-eosin, and alcian blue at pH 2.5) into a
      single procedure we have developed a stain that permits the optimal detection of
      H pylori in tissue sections while simultaneously allowing the histopathologic
      evaluation of all salient characteristics of the gastric mucosa. This procedure
      is inexpensive, as easy to perform as any silver stain, and provides consistent
      results. This stain is as sensitive as the Warthin-Starry stain for the detection
      of H pylori and significantly more sensitive than hematoxylin-eosin alone (> 99%
      v 85% when compared with the hematoxylin-eosin stain in a series of 332 positive
      biopsy specimens; > 99% v 61% in 49 biopsy specimens with rare bacteria). This
      stain is particularly useful for the visualization of small numbers of bacteria,
      such as in the evaluation of posttreatment gastric biopsy specimens, in specimens
      with abundant mucus or debris, and in specimens from the corpus, where H pylori
      usually does not elicit strong inflammatory responses and, therefore,
      pathologists' index of suspicion tends to be low.

PMID- 7512071
TI  - Immunocytochemical characterization of cell lines from human malignant
      mesothelioma: characterization of human mesothelioma cell lines by
      immunocytochemistry with a panel of monoclonal antibodies.
AB  - A panel of nine monoclonal antibodies was used to characterize human mesothelioma
      cell lines that we established from human malignant mesothelioma. The antigens
      detected were cytokeratin, vimentin, epithelial membrane antigen,
      carcinoembryonic antigen, Leu-M1 (CD15), desmin, factor VIII-related antigen (von
      Willebrand factor antigen), OV632, and ME1, a specific monoclonal antibody
      directed against human malignant mesothelioma. The technique used was the
      alkaline phosphatase anti-alkaline phosphatase method. All 30 cell lines, either
      epithelial, sarcomatous, or mixed, showed strong reactivity with cytokeratin and
      vimentin antibodies. None of the cell lines demonstrated any reactivity with
      carcinoembryonic antigen, Leu-M1, or factor VIII antibodies; moreover, all of 22
      cell lines studied were positive for ME1 antibody and 10 of 12 cell lines studied
      were positive for OV632. Some interesting features were noted: only two of the 30
      cell lines presented a weak positive staining with epithelial membrane antigen,
      and nine of 19 cell lines tested demonstrated a cytoplasmic staining pattern with
      desmin antibody. These results show that established human mesothelioma cell
      lines still possess the immunocytochemical characteristics that are basically
      consistent with the immunohistochemical features described in tumor tissues of
      malignant mesothelioma. These characteristics can be used to identify the
      mesothelioma cells grown from human malignant mesothelioma. Hence, the
      mesothelioma cell lines will provide a useful tool for the investigation of the
      cell biology of the tumor and the mechanisms of mesothelial cell transformation,
      as well as the in vitro evaluation of the effects of some drugs in order to
      develop new therapies for malignant mesothelioma.

PMID- 7512073
TI  - Diagnosis of pulmonary microvascular metastases by cytologic evaluation of
      pulmonary artery catheter-derived blood specimens.
AB  - Pulmonary microvascular tumor embolization is a recognized cause of respiratory
      distress in cancer patients that is rarely diagnosed antemortem. Previous studies
      with relatively few patients have reported high diagnostic yield using wedged
      pulmonary artery catheter-derived blood samples to evaluate dyspneic cancer
      patients for possible microembolization. From 1991 to 1993, 21 cancer patients
      with respiratory distress of relatively acute onset and varying severity who
      required pulmonary artery catheterization for hemodynamic monitoring were
      evaluated using this technique. Pulmonary microvascular cytology (PMC) was
      interpreted as positive for malignant cells in nine of 21 patients presenting
      with a range of tumor types, including carcinomas of the breast, colon, and
      pancreas as well as non-Hodgkin's lymphoma. In 11 patients the PMC was
      interpreted as negative. One case was considered nondiagnostic. Megakaryocytes,
      noted in most PMC specimens as well as in several samples of simultaneously drawn
      peripheral blood, may mimic epithelial tumor cells. Immunocytochemical stains for
      factor VIII and cytokeratins were used to resolve occasional diagnostic dilemmas.
      Clinical and/or pathologic follow-up information was available for all patients.
      Diagnostic accuracy was highest for epithelial malignancies. Two false-negative
      results occurred in patients with metastatic choriocarcinoma and breast
      carcinoma. Circulating malignant cells in the peripheral blood of a patient with
      non-Hodgkin's lymphoma led to one false-positive diagnosis. Benign lymphoid
      elements in PMC generally have a reactive and variable appearance that should not
      be misinterpreted as lymphoma. We conclude that PMC is a useful tool in the
      evaluation of dyspneic cancer patients requiring pulmonary artery catheterization
      for hemodynamic monitoring and its use potentially avoids additional diagnostic
      procedures.

PMID- 7512074
TI  - Strategies for improving the immunohistochemical staining of various intranuclear
      prognostic markers in formalin-paraffin sections: androgen receptor, estrogen
      receptor, progesterone receptor, p53 protein, proliferating cell nuclear antigen,
      and Ki-67 antigen revealed by antigen retrieval techniques.
AB  - Different variations of the antigen retrieval technique using different retrieval
      solutions have been evaluated for their effectiveness in restoring the
      antigenicity of six intranuclear antigens, each of which is a potentially
      valuable prognostic indicator in formalin-fixed, paraffin-embedded tissue
      sections. The results of immunohistochemical staining for estrogen receptor,
      progesterone receptor, androgen receptor, p53 protein, proliferating cell nuclear
      antigen, and Ki-67 antigen were compared following the different antigen
      retrieval approaches. The strongest immunostaining signal with the clearest
      background was obtained by microwave heating of dewaxed paraffin sections for 10
      minutes in 0.05 mol/L glycine HCl (pH 3.5) or in citrate buffer solution (pH 6).
      Urea solution, distilled water, and lead thiocyanate solution yielded
      improvements with some antigens, but less consistently and less impressively than
      glycine HCl buffer or citrate buffer. Following antigen retrieval nuclear
      staining was sharply defined and could be achieved consistently in a variety of
      tissues after formalin fixation for as long as 7 days. The duration of fixation,
      however, was an important variable; generally, the longer the fixation time the
      more vigorous the retrieval procedure required. This study demonstrates the
      ability to stain a variety of intranuclear antigens, which are not readily
      demonstrable otherwise, in formalin-paraffin sections with a high degree of
      consistency and reproducibility. The availability of methods that are effective
      in paraffin sections may facilitate studies of the possible value of these
      markers as prognostic indicators for predicting the response of major tumors to
      different forms of therapy. This study also provided insight into the basic
      principles of the antigen retrieval method, which may be helpful in attempts to
      develop a more uniformly standardized technique applicable to many different
      antigen systems.

PMID- 7512072
TI  - Pagetoid spread of intratubular germ cell neoplasia into rete testis: a
      morphologic and histochemical study of 100 orchiectomy specimens with invasive
      germ cell tumors.
AB  - Intratubular germ cell neoplasia (ITGCN) is now considered to be the preinvasive
      phase of testicular germ cell tumors with the exceptions of spermatocytic
      seminoma, pure yolk sac tumor, and mature teratoma. Pagetoid spread of ITGGN into
      rete testis is a common yet unpublished finding in these cases. We reviewed 100
      cases of testicular germ cell tumors from the Surgical Pathology service of
      Parkland Memorial Hospital (Dallas, TX) to evaluate the frequency of this pattern
      of spread. Additional sections were obtained from selected cases and were stained
      with anti-placental alkaline phosphatase, anti-low molecular weight keratin
      (clone AE1), and various lectins to highlight the process. Pagetoid spread of
      ITGCN into rete testis was identified in 24 of 60 cases (40%) in which histologic
      sections contained both ITGCN and rete testis. The incidence of pagetoid ITGCN
      involvement of the rete testis was lower in pure seminoma (seven of 25 cases
      [28%]) than in testes containing nonseminomatous germ cell tumors (17 of 35 cases
      [49%]). AE1 stained the epithelial cells of the rete testis but not the cells of
      the ITGCN, whereas placental alkaline phosphatase stained the neoplastic cells
      but not the epithelial cells of the rete testis. These stains were useful in
      delineating two cases in which the pagetoid involvement was so extensive that
      they were misdiagnosed as invasive seminomas. Pagetoid spread of ITGCN is a
      relatively common finding in testicular germ cell tumors and rarely can be
      mistaken for invasive seminoma. Immunohistochemistry can be helpful in
      distinguishing florid pagetoid spread from invasive seminoma.

PMID- 7512075
TI  - The tree of nursing.

PMID- 7512076
TI  - My most humorous moment in nursing.

PMID- 7512077
TI  - Micro-encapsulation of MDCK-ras-e cells prevents loss of E-cadherin invasion
      suppressor function in vivo.
AB  - The invasion-suppressor molecule E-cadherin mediates Ca(2+)-dependent cell
      aggregation and prevents invasion. E-cadherin-positive Madin-Darby canine kidney
      (MDCK) cells that were non-invasive in vitro formed, upon i.p. injection, tumors
      that were invasive. Differentiated tubular tumor areas showed an intense immuno
      signal for E-cadherin at intercellular contacts, whereas undifferentiated
      structures did not. Cell lines derived from such tumors turned out to be invasive
      in vitro and showed decreased Ca(2+)-dependent cell aggregation but no change in
      E-cadherin immunopositivity. This combination of phenotypes indicated a loss of
      the E-cadherin invasion-suppressor function. Micro-encapsulation of i.p.-injected
      cells prevented the loss of the E-cadherin invasion-suppressor function. We
      concluded that this loss in vivo was dependent upon immediate contacts between
      tumor cells and host cells or upon host factors that could not cross the capsule
      membrane.

PMID- 7512078
TI  - Synergistic effect of retinoids and interferon alpha on tumor-induced
      angiogenesis: anti-angiogenic effect on HPV-harboring tumor-cell lines.
AB  - Various retinoids and interferons exert anti-tumor effects both in experimental
      studies and in clinical trials. Recent reports indicate that they have a
      synergistic antineoplastic activity. Our study aimed to determine whether these
      synergistic anti-tumor effects are related to inhibition of tumor-cell-induced
      angiogenesis. A further aim was to compare the anti-angiogenic activity of
      various retinoids including 9-cis retinoic acid, a ligand for nuclear retinoic
      acid receptor RXR, given alone and in combination with interferon alpha-2a (IFN
      alpha-2a). An in vivo experimental model of cutaneous angiogenesis in the mouse
      was used. Angiogenesis was induced by intradermal injection of HPV16- or HPV18
      DNA-harboring tumor-cell lines. All-trans retinoic acid (all-trans RA), 13-cis
      retinoic acid (13-cis RA) and 9-cis retinoic acid (9-cis RA) as well as IFN alpha
      2a applied to mice intraperitoneally for 5 consecutive days before induction of
      angiogenesis resulted in significant inhibition of angiogenesis. Combination of
      retinoids with IFN alpha-2a led to a synergistic inhibition of angiogenesis, as
      compared to the effects of the drugs given alone. Similar results were obtained
      when tumor cells were preincubated in vitro with the compounds, before injection
      into untreated mice. Our findings on synergistic anti-angiogenic effects of
      retinoids and IFN alpha-2a could explain, at least partially, the anti-tumor
      efficacy of combined therapy with these agents, and provide support for the role
      of angiogenesis in tumor growth.

PMID- 7512079
TI  - Comparison of retinoic acid and phorbol myristate acetate as inducers of
      monocytic differentiation.
AB  - Several human myeloid leukemia cell lines growing in vitro can be induced to
      differentiate to more mature monocyte/macrophage-like cells by treatment with
      protein kinase C-activating phorbol esters, such as PMA. In addition to PMA,
      cells of the THP-1 myeloid leukemia cell line acquire macrophage-like
      characteristics after treatment with all-trans retinoic acid (RA). To analyze the
      signal transduction mechanisms induced by RA, we first compared the effects of
      PMA and RA on the expression of genes which are known to be regulated during
      monocytic differentiation. Both RA and PMA effectively down-regulated c-myc
      expression, while c-myb expression decreased only after PMA treatment. Expression
      of the beta 2-integrin genes, CD11a and CD11b, was clearly increased after both
      of these treatments. Their effects on the src-family tyrosine kinase genes were
      different: hck expression was similarly induced by these agents but lyn
      expression was stronger and more rapid after RA treatment. RA also enhanced lyn
      mRNA production rapidly in HL-60, indicating that the activation of lyn gene
      expression is common in monocytic and granulocytic maturation of myeloid leukemia
      cells. To examine whether the AP-1 enhancer activity is involved in RA-induced
      monocytic differentiation, THP-1 cells were transiently transfected with a
      chloramphenicol acetyl transferase (CAT)-reporter gene containing 5 copies of the
      AP-1 binding sites. In contrast to PMA, RA did not induce any CAT activity in
      these cells, thus suggesting that the RA-induced changes in the expression of
      those genes described above were not dependent on the AP-1 enhancer activity.

PMID- 7512080
TI  - Recombinant human granulocyte colony-stimulating factor augments cytotoxicity of
      OK-432-induced polymorphonuclear leukocytes.
AB  - Polymorphonuclear leukocytes (PMNs) recovered from the peritoneal cavity of mice
      treated with the streptococcal preparation OK-432, exhibited strong cytotoxicity
      after the in vitro addition of Nocardia rubra cell wall skeleton (N-CWS). In this
      study, we investigated whether recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) could augment the cytotoxicity of OK-432-induced PMNs after the
      addition of N-CWS in vitro. PMNs recovered from the peritoneal cavity of 8- to 10
      week-old, male C3H/He mice induced by intraperitoneal (i.p.) injection of 50
      KE/kg (1 KE = 0.1 mg) of OK-432 were used in a 51Cr release assay against MM46
      mammary carcinoma cells. While addition of rhG-CSF in vitro did not augment the
      cytotoxicity of OK-432-induced PMNs, marked augmentation of the cytotoxicity of
      OK-432-induced PMNs was observed following a single subcutaneous (s.c.) or i.p.
      injection of 125 micrograms/kg of rhG-CSF. The effect of in vivo administered rhG
      CSF was dependent on the timing of the injection with respect to OK-432
      administration and differed from s.c. or i.p. injections. Interestingly, the
      cytotoxicity of OK-432-induced PMNs was rather weak following consecutive s.c. or
      i.p. administration of rhG-CSF for 7-14 days. H2O2 is likely involved in
      mediating the cytotoxicity of OK-432-induced PMNs since activity was
      significantly reduced by the in vitro addition of low concentration of catalase.
      Generation of H2O2 by the PMNs correlated with cytotoxicity. These results
      suggest that in vivo administration of rhG-CSF augments the cytotoxicity of OK
      432-induced PMNs in a time dependent fashion and that H2O2 plays an important
      role in mediating their cytotoxicity.

PMID- 7512081
TI  - Antigenicity of three synthetic peptides from the C-terminus of HIV-1 gp 120
      correlates with the fragmentation pattern obtained in FAB mass spectrometry.
AB  - The proteolytic cleavage site of HIV-1 envelope glycoprotein precursor gp160 is
      sensitive to mutations. In this study we observed that the antigenicity of
      synthetic peptides from the C-terminus of gp120 is dependent on the length of the
      peptide, suggesting a conformational restriction. The physical properties of the
      peptides evaluated by FAB mass spectrometry correlated with the serological data,
      but differed from predictions based on the linear sequence. From our results we
      conclude that the C-terminus of HIV-1 gp120 is conformationally restricted.
      Furthermore FAB mass spectrometry seems to possess the ability to provide
      information concerning the conformation of synthetic peptides.

PMID- 7512082
TI  - [Hyalinosis cutis et mucosae and Ehlers-Danlos syndrome. A rare combination of
      syndromes].
AB  - We report on a 7-year-old boy suffering from two rare genetic diseases, namely
      hyalinosis cutis et mucosae and Ehlers-Danlos syndrome. The diagnosis was finally
      established after 7 years, by means of light and electron microscopy and
      immunohistology. Therefore, this report deals with the typical clinical and
      morphological features of both genetic disorders.

PMID- 7512083
TI  - The cryomicrotomy of rat dental tissues: a technique for histological and
      immunohistochemical analysis.
AB  - We have applied a method developed for the cryomicrotomy of non-decalcified bone
      to the histological preparation of the tooth and related dental tissues.
      Cryosections of rat mandible have been cut on a heavy-duty freezing microtome.
      Both cellular and extracellular structure was well preserved and the sections of
      tooth and bone appeared to be suitable for optical and scanning electron
      microscopy and for immunohistochemical analysis. However, there was an overall
      strong non-specific binding of immunohistochemical reagents to enamel which was
      not evident in the other mineralized tissues of the mandible. This may relate to
      important differences in the nature of this tissue.

PMID- 7512084
TI  - Immunohistochemistry of the intercellular matrix components and the epithelio
      mesenchymal junction of the human tooth germ.
AB  - The immunohistochemical localization of heparan sulphate, collagen type I, III
      and IV, laminin, tenascin, plasma- and cellular fibronectin was studied in tooth
      germs from human fetuses. The lamina basalis ameloblastica or membrana
      preformativa, which separates the pre-ameloblasts from the pre-dentin and dentin,
      contained heparan sulphate, collagen type IV, laminin and fibronectin. Enamel
      reacted with antifibronectin, but the reaction varied depending on the type of
      fibronectin and the source of antibody. In early pre-dentin, collagen type I,
      laminin, tenascin and fibronectin were present. In late pre-dentin and dentin
      collagen type I was found in intertubular dentin and in the zone between enamel
      and dentin. The close relationship between collagen type I in dentin and
      fibronectin in immature enamel is interesting, as it may contribute to the
      stabilization of the amelodentinal interface. In dental pulp, collagen type IV
      and laminin were found in the endothelial basement membranes. Collagen type I and
      III, tenascin and fibronectin were localized to the mesenchymal intercellular
      matrix. The results of this study have supported the assumption that the lamina
      basalis ameloblastica is a basement membrane, and have lead to the suggestion
      that ameloblasts are producers of fibronectin or a fibronectin-like substance.

PMID- 7512085
TI  - A comparative study on tissue processing procedures for the immunohistochemical
      investigation of oral mucosal Langerhans cells.
AB  - An immunoperoxidase technique was used to compare wax-embedded tissue with frozen
      tissue for quantitative immunohistochemistry of oral mucosal Langerhans cells.
      Initial experiments using anti-CD1a, -HLADR and -S100 antisera showed that
      phenotype, fixative, antibody dilution and trypsinisation of the tissue section
      significantly affected Langerhans cell counts. Only the anti-HLADR antibody
      detected Langerhans cells in both frozen and wax-embedded sections. Some 38% of
      S100-positive dendritic cells were situated in the stratum basale, and 41-84% of
      these contained melanin as determined by double-labelling. Sections from 39
      volunteers were then reacted with the anti-CD1a and -HLADR antibodies. The
      morphology of Langerhans cells was more dendritic in frozen sections, and the
      mean HLADR-positive Langerhans cells count in frozen sections was significantly
      higher than that in wax-embedded sections from the same individual. The intra
      individual ratio of counts between frozen and wax-embedded sections was variable;
      hence, the apparent loss of HLADR antigenicity as a result of tissue processing
      was unpredictable. Counts of CD1a-positive Langerhans cells were consistently
      higher. We conclude that the use of anti-CD1a antibody on frozen tissue is the
      optimum method for quantitative studies of oral mucosal Langerhans cells, and
      that such studies performed on wax-embedded tissue may be unreliable.

PMID- 7512086
TI  - Calcium and calmodulin inhibit phosphorylation of a novel auditory nerve protein.
AB  - The growing use of cochlear prosthetic devices and demonstrations of direct
      ototoxic insult to spiral ganglion neurons make it imperative to gain an
      understanding of intracellular biochemical regulation in primary sensory neurons.
      Calcium and calmodulin regulate many aspects of neuronal cellular physiology
      through stimulation of protein kinase activity. We have previously demonstrated
      the presence of calmodulin-dependent protein kinase substrates in the guinea pig
      modiolus and, additionally, the presence of two proteins (12 kDa and 81 kDa,
      designated as p12 and p81) whose phosphorylation is blocked by calcium and
      calmodulin (Coling and Schacht, 1991). Here, we investigate three models for this
      unusual regulatory mechanism. The effects of calcium, calmodulin and
      trifluoperazine on dephosphorylation of both proteins suggests that calmodulin
      inhibits protein kinase activity. P81 was identified by immunoprecipitation as
      the myristoylated alanine-rich C kinase substrate (MARCKS), a ubiquitous actin
      binding protein. Two observations indicate that MARCKS may be regulated
      differently in acoustic nerve than in cerebral cortex. 32P incorporation was
      significantly higher in acoustic nerve than in brain. The calmodulin-dependent
      block of MARCKS phosphorylation was observed only in acoustic nerve. p12 shares
      several characteristics with myelin basic protein (MBP). We used a double label
      assay with 32P autoradiography and immunoblotting to show that p12 is in fact
      distinct from MBP. We suggest that either p12 or p12 kinase may be either
      specific to the peripheral auditory system or novel marker proteins for that
      tissue.

PMID- 7512087
TI  - Clinical relevance of breast cancer biology.
AB  - Biological properties of breast cancer are reviewed in relation to their ability
      to provide information about etiology, prognosis, or response to therapy. The
      authors suggest guidelines for the rigorous and systematic evaluation of biologic
      factors in relation to the prognosis and treatment of breast cancer.

PMID- 7512090
TI  - Simultaneous analysis of homovanillic acid, 5-hydroxyindoleacetic acid, 3-methoxy
      4-hydroxyphenylethylene glycol and vanilmandelic acid in plasma from alcoholics
      by high-performance liquid chromatography with electrochemical detection.
      Critical comparison of solid-phase and liquid-liquid extraction methods.
AB  - A method is described for the simultaneous determination of vanilmandelic acid, 3
      methoxy-4-hydroxyphenylethylene glycol, 5-hydroxyindoleacetic acid, and
      homovanillic acid in a human plasma sample using reversed-phase high-performance
      liquid chromatography with column switching and amperometric detection. Two
      methods of sample preparation were tested. Liquid-liquid extraction yields better
      recoveries, is more selective and precise than solid-phase extraction and allows
      a shorter time of chromatographic analysis. Estimated plasma values of the
      metabolites from healthy controls are in good agreement with previously reported
      levels. Studies of alcoholics at the beginning of the delirium tremens provided
      different plasma levels of the metabolites, dependent on the different duration-
      and hence the severity--of the delirium.

PMID- 7512088
TI  - Angiogenesis and breast cancer.
AB  - Antiangiogenesis is an appealing therapeutic modality for the treatment of a
      number of clinically important diseases, including human malignancies and
      specifically breast cancer. For years, such an approach has remained little more
      than good theory. However, recent studies have suggested that specific
      antiangiogenic agents might be effective and safe, and preliminary clinical
      trials are now being planned to test these drugs. Although early studies will be
      designed to test the safety of these agents, it seems most likely that they will
      have their greatest efficacy early in the course of the disease, for example, in
      the adjuvant setting. Moreover, they will almost certainly be most active when
      used in combination, both with other antiangiogenic agents and with other
      modalities such as classic chemotherapy or endocrine therapies or both. Given the
      potential for monitoring tissue neovascularization and circulating angiogenic
      factors, one might also speculate that therapies might be chosen based on
      specific, individual characteristics, not unlike the current use of tumor steroid
      hormone receptor content to determine the appropriate use of endocrine therapy.
      In fact, individual responses to antiangiogenic molecules may be important. For
      example, one group of investigators investigated antiangiogenic activity of a
      large, polyglycosylated lipid, maltose tetrapalmitate (MTP). They found that the
      genetic ability of inbred mice to respond to MTP is specifically related to the
      antiangiogenic and antitumor effects of MTP. Mice genetically unable to respond
      to MTP were not protected from tumor-graft growth by MTP, whereas responders
      survived for long periods of time. Although the clinical field of antiangiogenic
      therapy remains in its infancy, physicians in the future may be as concerned
      about the "angiogenic profile" of individual patients as they are today about
      clinical staging and ER status.

PMID- 7512091
TI  - Distribution of tenascin in normal cycling human ovary.
AB  - Tenascin is an extracellular matrix glycoprotein, which has been reported to be
      involved in parenchymal-mesenchymal interactions during morphogenesis, wound
      healing, and carcinogenesis. Tenascin immunolocalization was performed in 51
      specimens of morphologically normal human ovaries by using a specific monoclonal
      antibody against purified human fibroblast tenascin. In preovulatory follicles,
      no significant immunoreactivity was detected. In functioning corpora lutea,
      immunoreactivity was present as a fine border around the periphery. In
      association with the involution of the corpora lutea, marked diffuse tenascin
      immunostaining in the intercellular space was observed. These data raise the
      question of whether tenascin may be involved in luteolysis and may play an
      important role in the ovarian cycle by regulating the involution of corpora
      lutea.

PMID- 7512089
TI  - Effect of longitudinal muscle-myenteric plexus removal and indomethacin on the
      response to tachykinin NK-2 and NK-3 receptor agonists in the circular muscle of
      the guinea-pig ileum.
AB  - 1. The effect of removal of the longitudinal muscle-myenteric plexus (LM-MP)
      and/or indomethacin (10 microM) on the response to the tachykinin NK-2 receptor
      selective agonist, [beta Ala8]NKA(4-10), or to the NK-3 receptor selective
      agonist, senktide, was investigated by measuring mechanical activity (isotonic
      recording) of circular muscle (ring preparation) of the guinea-pig ileum. 2.
      Indomethacin (10 microM) increased the percentage of ileal rings displaying
      spontaneous activity, either intact or LM-MP-free. The response to senktide (10
      nM and 1 microM) was lower in LM-MP-free than in intact ileal rings, either in
      the absence or presence of indomethacin. The response to a low concentration (10
      nM) of [beta Ala8] NKA (4-10) was enhanced in LM-MP-free rings and by
      indomethacin. 3. In intact ileal rings, the response to senktide was unaffected
      by atropine (3 microM) alone or by the tachykinin NK-2 receptor antagonist MEN
      10,376 (10 microM) alone while it was reduced by the combined administration of
      the two antagonists. The response to senktide was greatly reduced by tetrodotoxin
      (TTX, 1 microM). Senktide-induced contractions (10 nM) were also reduced by the
      blocker of N-type voltage-sensitive calcium channels, omega-contoxin (CTX, 0.1
      microM). 4. In about 30% of preparations tested, an inhibitory response (decrease
      in spontaneous activity) to 10 nM senktide, was disclosed in CTX-treated intact
      ileal rings. This inhibitory effect was TTX-sensitive. 5. In LM-MP-free ileal
      rings, the response to senktide was abolished or reduced by atropine and MEN
      10,376, alone or in combination, and was also reduced or abolished by TTX and
      CTX. 6. The response to [beta Ala8]NKA (4-10) was inhibited by MEN 10,376, in
      both intact and LM-MP-free ileal rings while it was unaffected by atropine, TTX
      or CTX. 7. These results indicate that indomethacin pretreatment induces a
      regular background activity for studying the motor response to tachykinins in the
      circular muscle of the ileum, probably by blocking the formation of relaxant
      prostanoids. A further increase in sensitivity to direct smooth muscle
      stimulation (NK-2 receptor agonist) can be obtained by removal of the LM-MP. The
      response to NK-3 receptor stimulation is diminished but not abolished by removal
      of the LM-MP, suggesting that NK-3 receptors are located on neuronal bodies of
      myenteric neurons, but possibly also at other sites (possibly, nerve
      terminals).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7512092
TI  - Expression of perforin, granzyme A and TIA-1 by human uterine CD56+ NK cells
      implies they are activated and capable of effector functions.
AB  - At the time the human placenta is established, the uterine mucosal lining
      (decidua) is infiltrated by abundant CD3- CD56bright natural killer (NK) cells.
      NK cells circulating in blood are known to contain perforin and granzyme A in
      their cytoplasmic granules. TIA-1, an RNA-binding protein capable of inducing DNA
      fragmentation, has also been found in the granules of cytolytic cells. In this
      paper, we demonstrate the presence of perforin, granzyme A and TIA-1 in the
      granules of uterine NK cells. Sixteen sections of non-pregnant endometrium
      throughout the menstrual cycle and six sections of early decidua, together with
      cytospins of four preparations of isolated decidual leukocytes were stained by
      both immunohistology and immuno-electron microscopy to localize perforin,
      granzyme A and TIA-1 to the cytoplasmic granules of CD56+ cells. The presence in
      vivo of these cytolytic molecules in a normal physiological situation implies
      that these uterine NK cells may have effector functions in the control of normal
      placentation.

PMID- 7512093
TI  - PCR primers and probes for the 16S rRNA gene of most species of pathogenic
      bacteria, including bacteria found in cerebrospinal fluid.
AB  - A set of broad-range PCR primers for the 16S rRNA gene in bacteria were tested,
      along with three series of oligonucleotide probes to detect the PCR product. The
      first series of probes is broad in range and consists of a universal bacterial
      probe, a gram-positive probe, a Bacteroides-Flavobacterium probe, and two probes
      for other gram-negative species. The second series was designed to detect PCR
      products from seven major bacterial species or groups frequently causing
      meningitis: Neisseria meningitidis, Haemophilus influenzae, Streptococcus
      pneumoniae, S. agalactiae, Escherichia coli and other enteric bacteria, Listeria
      monocytogenes, and Staphylococcus aureus. The third series was designed for the
      detection of DNA from species or genera commonly considered potential
      contaminants of clinical samples, including cerebrospinal fluid (CSF): Bacillus,
      Corynebacterium, Propionibacterium, and coagulase-negative Staphylococcus spp.
      The primers amplified DNA from all 124 different species of bacteria tested.
      Southern hybridization testing of the broad-range probes with washes containing 3
      M tetramethylammonium chloride indicated that this set of probes correctly
      identified all but two of the 102 bacterial species tested, the exceptions being
      Deinococcus radiopugnans and Gardnerella vaginalis. The gram-negative and gram
      positive probes hybridized to isolates of two newly characterized bacteria,
      Alloiococcus otitis and Rochalimaea henselii, as predicted by Gram stain
      characteristics. The CSF pathogen and contaminant probe sequences were compared
      with available sequence information and with sequencing data for 32 different
      species. Testing of the CSF pathogen and contaminant probes against DNA from over
      60 different strains indicated that, with the exception of the coagulase-negative
      Staphylococcus probes, these probes provided the correct identification of
      bacterial species known to be found in CSF.

PMID- 7512095
TI  - Use of restriction fragment polymorphism analysis of rRNA genes to assign species
      to unknown clinical isolates of oral viridans streptococci.
AB  - This study evaluated restriction fragment length polymorphisms of rRNA genes
      (ribotyping) for genotypic identification of 53 oral isolates classified as
      "Streptococcus sanguis" by colony morphology. Isolates were from 8-h buccal
      plaque on lower first permanent molars of 20 subjects. DNA was digested with
      AatII and hybridized with digoxygenin-labeled cDNA of Escherichia coli 16S and
      23S rRNA. Strains were ribotyped again with AlwNI or PvuII on the basis of the
      presence or absence of a 2,290-bp AatII band. Band patterns were compared with
      reference ribotypes for Streptococcus gordonii, Streptococcus sanguis,
      Streptococcus crista, Streptococcus oralis, Streptococcus mitis, and
      Streptococcus parasanguis strains. Forty-eight isolates could be assigned to a
      species (22 S. sanguis, 14 S. oralis, 12 S. gordonii). Multiple species were seen
      in 14 subjects; multiple strains of the same species occurred in 11 subjects. Our
      findings suggest that ribotyping can be used for genotypic identification of S.
      sanguis, S. oralis, and S. gordonii isolates.

PMID- 7512096
TI  - An integrated target sequence and signal amplification assay, reverse
      transcriptase-PCR-enzyme-linked immunosorbent assay, to detect and characterize
      flaviviruses.
AB  - We previously described a reverse transcriptase-PCR using flavivirus genus
      conserved and virus species-specific amplimers (D. W. Trent and G. J. Chang, p.
      355-371, in Y. Becker and C. Darai; ed., Frontiers of Virology, vol. 1, 1992).
      Target amplification was improved by redesigning the amplimers, and a sensitive
      enzyme-linked immunosorbent assay (ELISA) technique has been developed to detect
      amplified digoxigenin (DIG)-modified DNA. A single biotin motif and multiple DIG
      motifs were incorporated into each amplicon, which permitted amplicon capture by
      a biotin-streptavidin interaction and detection with DIG-specific antiserum in a
      colorimetric ELISA. We evaluated the utility of this assay for detecting St.
      Louis encephalitis (SLE) viral RNA in infected mosquitoes and dengue viral RNA in
      human serum specimens. The reverse transcriptase-PCR-ELISA was as sensitive as
      isolation of SLE virus by cell culture in detecting SLE viral RNA in infected
      mosquitoes. The test was 89% specific and 95 to 100% sensitive for identification
      of dengue viral RNA in serum specimens compared with isolation of virus by Aedes
      albopictus C6/36 cell culture and identification by the indirect
      immunofluorescence assay.

PMID- 7512094
TI  - Construction of polyepitope fusion antigens of human cytomegalovirus ppUL32:
      reactivity with human antibodies.
AB  - We have previously shown that single linear epitopes of the major human
      cytomegalovirus (HCMV) antigens, expressed as fusion proteins or synthesized as
      oligopeptides, can be valuable diagnostic material in the serology of HCMV
      infection (M. P. Landini, M. X. Guan, G. Jahn, W. Lindenmaier, M. Mach, A.
      Ripalti, A. Necker, T. Lazzarotto, and B. Plachter, J. Clin. Microbiol. 28:1375
      1379, 1990; M. P. Landini, T. Lazzarotto, A. Ripalti, M. X. Guan, and M. La
      Placa, J. Clin. Microbiol. 27:2324-2327, 1989; A. Ripalti, M. P. Landini, E. S.
      Mocarski, and M. La Placa, J. Gen. Virol. 70:1247-1251, 1989). In this work we
      addressed the question of whether the expression of more than one linear epitope
      on a single fusion protein could increase the reactivity of genetically
      engineered antigenic material with human antibody. To answer this question we
      fused sequences expressing two different epitopes contained in the basic
      phosphoprotein of 150 kDa encoded by UL32 (M. S. Chee, A. T. Bankier, S. Beck, R.
      Bohni, C. M. Brown, T. Cerny, T. Hornsel, C. A. Hutchinson, T. Kouzarides, J. A.
      Martignetti, and B. G. Barrell, Curr. Top. Microbiol. Immunol. 154:125-169, 1990;
      G. Jahn, T. Kouzarides, M. Mach, B.-C. Scholl, B. Plachter, B. Traupe, E.
      Preddie, S. C. Satchwell, B. Fleckenstein, and B. G. Barrell, J. Virol. 61:1358
      1367, 1987), ppUL32, which was repeatedly shown to be the strongest immunogen
      present in the viral particle. We also made fusions with sequences expressing a
      single epitope repeated once, twice, or three times. The different fusion
      proteins were tested with HCMV-positive human sera. We found that fusion proteins
      expressing different epitopes together were recognized by a larger number of
      serum specimens and with more intense reactions in Western blot (immunoblot)
      experiments. We also found evidence that expression on the same polypeptide of
      the two distinct epitopes produced a stronger antigen than the mere addition of
      two fusion proteins which each carried one copy of one of these epitopes.
      Furthermore, we found that while the same epitope expressed two or three times on
      the same fusion protein was not better recognized by immunoglobulin G than the
      single epitope, immunoglobulin M reactivities to the double and triple epitopes
      were enhanced.

PMID- 7512098
TI  - Cross-reactivity of genetic probe for detection of Mycobacterium tuberculosis
      with newly described species Mycobacterium celatum.
AB  - An acridinium ester-labeled DNA probe (AccuProbe; Gen-Probe Inc., San Diego,
      Calif.) for the identification of the Mycobacterium tuberculosis complex gave
      discrepant results with the newly described species M. celatum. Examination of 20
      strains of M. celatum showed that 8 were positive with the probe; the remaining
      12 were negative.

PMID- 7512099
TI  - Identification of antigenic differences of recombinant and pituitary bovine
      growth hormone using monoclonal antibodies.
AB  - For characterization and determination of recombinant bovine GH (rbGH) eight
      monoclonal antibodies (MAb) were produced against rbGH from Monsanto. The various
      MAb showed different affinities to rbGH, pituitary bovine GH (pbGH), and
      pituitary ovine GH (poGH). With epitope analysis several MAb were shown to
      recognize different epitopes of rbGH. The MAb MUC-rbGH-3A11 and MUC-rbGH-1E5 were
      used to develop a Sandwich ELISA. By checking the specificity of the assay no
      cross reactivity was found with pituitary porcine GH, pituitary human GH, bovine
      or ovine prolactin and little cross reactivity with poGH could be found. The
      Sandwich ELISA detected various rbGH (Monsanto, Elanco, Cyanamid) with different
      N-terminal amino acids and discriminated between rbGH and pituitary bovine GH by
      an affinity factor of 2.0. The detection level was 2 ng rbGH per ml PBS buffer.
      The recovery was about 86% in bovine serum. It might therefore be possible to
      detect rbGH-treated cows using a Sandwich ELISA, but this would need a field
      study.

PMID- 7512097
TI  - Identification of a highly cross-reactive outer surface protein B epitope among
      diverse geographic isolates of Borrelia spp. causing Lyme disease.
AB  - The outer surface lipoprotein B (OspB) of Borrelia burgdorferi is a major
      component of the borrelial protein profile and has been shown to be highly
      immunogenic in experimentally immunized and infected mammals. However, the ospB
      loci of different strains show considerable heterology at the nucleic acid
      sequence level, and the progeny of a clonal strain of B. burgdorferi exhibited
      OspB polymorphisms with respect to apparent molecular weights and reactivities
      with monoclonal antibodies. These data suggest that OspB is not a good candidate
      for vaccination or diagnostic purposes. The present study describes a monoclonal
      antibody, designated 84C, directed against a very highly conserved domain of the
      OspB lipoprotein. Western immunoblot analysis with 84C demonstrated reactivity in
      84.2% of human, tick, and other vertebrate isolate strains examined from widely
      diverse geographic regions, including strains of B. burgdorferi sensu stricto and
      two closely related species, B. garinii and B. afzelii. The 84C-binding region
      was delimited to a highly conserved 11-amino-acid region in the carboxyl terminus
      of OspB as demonstrated by (i) DNA sequence analysis of wild-type and 84C
      resistant mutant ospB alleles and (ii) deletion mutagenesis of a recombinant ospB
      gene in Escherichia coli. Finally, the 84C epitope was demonstrated to be exposed
      on the borrelial surface in situ as (i) the monoclonal antibody 84C was able to
      agglutinate borrelias in culture and (ii) 84C-resistant escape variants were
      isolated. These data suggest that the potential value of OspB as a vaccine
      candidate or diagnostic tool be examined more closely, in the context of the 84C
      reactive domain.

PMID- 7512100
TI  - The effect of chronic alprazolam on sleep and bioamine metabolites in depression.
AB  - Alprazolam administered for 43 days in doses of 6 to 10 mg/day had an
      antidepressant effect in four of nine depressed patients. Decreases in slow wave
      sleep, increases in rapid eye movement (REM) latency, and decreases in REM
      minutes and percent and REM sleep eye movements were found in the group as a
      whole. The drug had a general hypnotic effect with a trend toward increased total
      sleep time. Nonsignificant changes in the concentrations of 3-methyl-4
      hydroxyphenylglycol and homovanillic acid in the cerebrospinal fluid (CSF) were
      qualitatively similar to those found after treatment with tricyclic
      antidepressant drugs; however, only the larger decreases in CSF 5
      hydroxyindoleacetic acid achieved statistical significance. Baseline sleep and
      CSF metabolites and changes in these measures on drug did not predict the
      therapeutic effects of alprazolam.

PMID- 7512101
TI  - The effect of terfenadine on unilateral nasal challenge with allergen.
AB  - To investigate the role of H1 receptor-mediated effects in allergic rhinitis, we
      challenged 12 allergic volunteers with allergen 2 hours after administration of
      either placebo or 60 mg of terfenadine. Filter paper discs were used for the
      unilateral administration of allergen and the collection of nasal secretions.
      Secretion weights, levels of histamine in recovered nasal secretions, and nasal
      airway resistance (NAR) were measured for each nostril separately, and the number
      of sneezes was counted. After placebo treatment, allergen challenge led to
      significant increases in ipsilateral and contralateral secretion weights,
      ipsilateral histamine levels, ipsilateral NAR, and sneezing. Contralateral
      histamine levels were not elevated. H1 antagonism with terfenadine markedly
      reduced the number of sneezes and partially decreased ipsilateral and
      contralateral secretion weights, without affecting the increase in NAR.
      Terfenadine premedication also lowered the amount of histamine in ipsilateral
      secretions after allergen challenge. Performing identical nasal challenges with a
      10-fold lower dose of antigen produced similar results. Previous studies showed
      that terfenadine had no effect on methacholine provocation and completely
      abolished ipsilateral and contralateral secretion weights after histamine
      challenge. We conclude that sneezing after allergen challenge is caused almost
      exclusively by a reflex initiated through H1 receptors and that H1 antagonism has
      no influence on allergen-induced increases in NAR. Unilateral allergen challenge
      leads to bilateral increases in secretion weights, which are only partially
      inhibited by terfenadine, suggesting the involvement of mediators other than
      histamine in the nasonasal reflex. As reported earlier, terfenadine also
      decreases allergen-induced histamine release after challenge with the highest
      dose of antigen.

PMID- 7512102
TI  - Molecular characterization of dog albumin as a cross-reactive allergen.
AB  - Indoor allergens comprise a group of allergenic proteins that are commonly
      derived from house dust mite and cat and dog dander. In addition to the two major
      dog allergens (molecular weights: 19 and 23 kd), dog albumin represents an
      important allergen for up to 35% of patients who are allergic to dogs. In IgE
      immunoblot inhibition studies and histamine release tests it has been
      demonstrated that patients who react to dog albumin exhibit IgE reactivity with
      purified albumins from cat, mouse, chicken, and rat. The proportion of dog
      specific IgE directed against dog albumin was determined for patients allergic to
      dog albumin, and it ranges from 70% to 90%. By IgE immunoscreening of a lambda
      gt11 expression library from a dog salivary gland, we identified a number of
      reactive complementary DNA clones. All patients with IgE reactivity against
      natural dog albumin displayed IgE reactivity to the beta-galactosidase fusion
      protein encoded by clone 54c, which was therefore assumed to contain major IgE
      epitopes of dog albumin. The deduced amino acid sequence of clone 54c was
      compared with the Swiss-Prot library, and significant sequence homologies were
      found with albumins from different species (human: 82.6%, pig: 81.8%, cattle:
      77.3%, sheep: 78.8%, mouse: 75.8%, and rat: 76.2%). Several other IgE-positive
      clones hybridized with oligonucleotides that were prepared according to this
      sequence. Partial complementary DNA coding for dog albumin fragments may be
      considered a useful tool for further characterization of major IgE epitopes of
      dog albumin.

PMID- 7512104
TI  - Enhancement of IgE production by anti-CD40 antibody in atopic dermatitis.
AB  - It has been recently recognized that the obligate requirement for T cells in the
      development of IgE responses can be substituted for by anti-CD40 antibody. In
      this study of patients with atopic dermatitis and high IgE levels, we have
      analyzed the role of the CD40 molecule in IgE production. Costimulation of
      peripheral blood mononuclear cells (PBMCs) from normal donors with interleukin-4
      (IL-4) and anti-CD40 monoclonal antibody resulted in a selective increase in IgE
      production; either reagent alone, however, was ineffective. In contrast, addition
      of anti-CD40 monoclonal antibody alone to PBMCs or B cells from patients with
      atopic dermatitis markedly increased IgE production, even in the absence of
      exogenous IL-4. With the use of an ELISA spot assay, this increase in IgE
      production was attributed to an expansion of IgE-secreting B cells. In anti-IgM
      stimulated lymphocyte cultures from patients with atopic dermatitis the
      costimulation with anti-CD40 induced strong lymphocyte proliferation. Similar
      results were observed with anti-IgM plus IL-4. The augmentation induced by anti
      CD40 was inhibited by addition of anti-IL4 to anti-CD40-treated atopic dermatitis
      cells. In normal subjects the effects of anti-CD40 alone on IgE production could
      be observed after pretreatment of normal PBMCs with IL-4 for 3 days. The effects
      of anti-CD40 in atopic dermatitis may be explained in part by differences in CD40
      expression. In freshly isolated PBMCs from patients with atopic dermatitis, the
      mean fluorescence intensity of CD40 expression on B cells was increased when
      compared with PBMCs from nonatopic donors, ans stimulation of normal or atopic
      dermatitis PBMCs with IL-4 increased the intensity of CD40 staining of cells.

PMID- 7512105
TI  - Measurement of gluten using a monoclonal antibody to a sequenced peptide of alpha
      gliadin from the coeliac-activating domain I.
AB  - A monoclonal antibody, raised against a sequenced 54 amino-acid peptide from the
      coeliac-activating N-terminal region of alpha-gliadin, was used in an assay for
      the measurement of gluten in foods. A double-sandwich ELISA using a polyclonal
      capture antibody produced standard curves for unfractionated gliadin and its
      alpha, beta, gamma and omega subfractions, and for rye, barley and oat prolamins.
      The sensitivity of the assay for unfractionated gliadin and rye prolamins was 15
      ng/ml, for barley and oat prolamins 125 and 250 ng/ml, respectively. Prolamins
      from coeliac non-toxic rice, maize, millet and sorghum did not cross-react in the
      assay.

PMID- 7512103
TI  - An immunogenetic analysis of T-cell reactive regions on the major allergen from
      the house dust mite, Der p I, with recombinant truncated fragments.
AB  - Proliferation assays were used to localize the T-cell reactive sites on the major
      allergen from the house dust mite Dermatophagoides pteronyssinus, Der p I. Seven
      overlapping recombinant fragments of the Der p I molecule, synthesized with the
      pGEX expression vector system, were used to stimulate peripheral blood
      lymphocytes from 35 HDM-sensitive individuals. The fusion fragments were from 39
      to 114 amino acids in length and spanned the entire Der p I molecule. Significant
      proliferative responses to one or more of the fragments were evident in 18 of the
      allergic individuals, and each of the fragments led to T-cell stimulation in at
      least one of the subjects. Although T-cell reactive regions were located
      throughout the molecule, in 12 of the 18 responsive individuals, major
      immunogenic sites were contained within the 56 amino acids of the N-terminus, and
      in 11 of these individuals T-cell reactive regions were only present between
      amino acid positions 1 and 94. In two individuals reactive sites could be mapped
      in the C-terminal half of the molecule, and in five subjects, epitopes were
      present in both N- and C-terminal regions. HLA class I and class II DR and DQ
      specificities were determined serologically in 16 of the 18 individuals, and no
      strong pattern of association between HLA type and the T-cell immunogenic region
      could be detected.

PMID- 7512106
TI  - Cerebral white-matter changes suggesting leukodystrophy in ataxia telangiectasia.
AB  - Ataxia telangiectasia is an autosomal recessive disorder characterized by
      progressive cerebellar ataxia, recurrent sinopulmonary infections, oculocutaneous
      telangiectasia, selective immunoglobulin deficiency, and defective cellular
      immunity. We report a 4-year-old girl with ataxia telangiectasia whose initial
      magnetic resonance imaging (MRI) scan at 17 months of age showed
      leukoencephalopathy compatible with a leukodystrophy, a neuroimaging feature of
      ataxia telangiectasia that has not been described. Ataxia telangiectasia was not
      suspected until the child developed more typical clinical features. Diffuse white
      matter high signal intensity on T2-weighted MRI scans may occur in the early
      stages of ataxia telangiectasia. This disease should be considered in the
      differential diagnosis of any child with a history and MRI findings suggestive of
      one of the leukodystrophies. The nonneurologic manifestations of ataxia
      telangiectasia may be of help diagnostically in this clinical setting.

PMID- 7512107
TI  - Isolated glycerol kinase deficiency in a neonate.
AB  - Glycerol kinase deficiency occurs either as a relatively benign isolated enzyme
      deficiency, or as part of a syndrome resulting from a microdeletion in the p21
      region of the X chromosome associated with congenital adrenal hypoplasia and/or
      Duchenne muscular dystrophy. Developmental delay is a consistent feature of the
      microdeletion syndrome but not of the isolated enzyme defect. We report a case of
      isolated glycerol kinase deficiency in a neonate presenting with hypotonia,
      apnea, mild developmental delay, and glyceroluria, without evidence of adrenal
      insufficiency or myopathy. A mild communicating hydrocephalus was noted on
      magnetic resonance imaging brain scan. It is important, therefore, to exclude
      glyceroluria in infants being investigated for apnea and hypotonia.

PMID- 7512108
TI  - Epilepsy, language, and behavior: clinical models in childhood.
AB  - The complex relationship between epilepsy, language, and behavior is not well
      understood. Neurologic disorders such as Landau-Kleffner syndrome, electrical
      status epilepticus during slow-wave sleep, infantile spasms, Lennox-Gastaut
      syndrome, tuberous sclerosis, autism, and developmental language disorders are
      useful clinical models in the investigation of this complex relationship. These
      disorders are reviewed in terms of their contribution to our present knowledge of
      the relationship between epilepsy, language, and behavior. Present management
      issues and directions for future research are discussed.

PMID- 7512109
TI  - Transient expression of tenascin in experimentally induced cholestatic fibrosis
      in rat liver: an immunohistochemical study.
AB  - This study describes the sequential changes in tenascin expression in hepatic
      fibrosis induced by bile duct ligation (BDL) in the rat. Two days after BDL,
      tenascin was strongly expressed in the matrix surrounding interlobular bile ducts
      and also between proliferating ductules. From day 7 onwards, its distribution was
      restricted to the connective tissue-parenchymal interfaces where ductular
      proliferation was still active. A markedly increased number of desmin- and alpha
      smooth muscle actin (alpha-smA)-positive cells, considered myofibroblasts, was
      noted around interlobular bile ducts and between proliferating ductules during
      periductal fibrogenesis. Type IV collagen and laminin were strongly expressed on
      the basement membranes of proliferating ductules, and contributed to the
      development of newly formed fibrous septa. The transient expression of tenascin
      around interlobular bile ducts in the early phase of BDL may be related to the
      onset of periductal fibrosis or to the mitogenic response of the biliary
      epithelium. The expression of tenascin between 'proliferating' ductules in
      contrast to its absence from 'mature' fibrous areas suggests a transient role in
      early matrix organization. Furthermore, alpha-smA-positive cells may modulate the
      synthesis of extracellular matrix components.

PMID- 7512111
TI  - Monitoring the natural course and response to therapy of chronic hepatitis B with
      an automated semi-quantitative assay for IgM anti-HBc.
AB  - The clinical significance of a semi-quantitative microparticle enzyme immunoassay
      (IMx Core-M, Abbott) was evaluated for detection of IgM-class antibodies against
      the hepatitis B core antigen (IgM anti-HBc) in 136 hepatitis B surface antigen
      (HBsAg) positive individuals (96 chronic HBV carriers, 20 patients with chronic
      HBV-HDV infections and 20 patients with acute hepatitis B) and 50 HBV-negative
      controls. Baseline and follow-up sera (4-11 samples) were analysed from 79
      carriers with chronic hepatitis B, 44 of whom were treated with interferon. IMx
      indexes above 3,000 were found in 95% of the acute hepatitis B patients and above
      0.300 in 91.5% of patients with ongoing chronic hepatitis B. IMx indexes between
      0.200 and 0.300 were observed in (a) patients with recent HBeAg to anti-HBe
      seronconversion (6-12 months) and normal serum ALT levels, (b) patients immuno
      tolerant to HBV infection and without liver disease despite high levels of
      viremia, and (c) patients with anti-HBe-positive chronic hepatitis B during 7-13
      month intervals of asymptomatic carriage between episodes of disease
      reactivation. IMx indexes below 0.200 were detected in all HBV-negative
      individuals and healthy HBV carriers, in 14 (70%) of 20 chronic hepatitis D
      patients and in all but 1 of 22 interferon-treated patients with histological
      remission of liver disease, 5-12 months after clearance of viremia and
      normalization of serum ALT levels. In contrast, IMx indexes remained above 0.200
      in all patients with hepatitis B reactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512110
TI  - Histologically advanced chronic hepatitis C treated with recombinant alpha
      interferon: a randomized placebo-controlled double-blind cross-over study.
AB  - Chronic hepatitis C is common in Saudi Arabia and most often presents in an
      advanced stage. To assess the response of patients to interferon, a randomized
      placebo-controlled double-blind study was undertaken. All but 1 patient had
      cirrhosis or fibrosis before interferon. After a 24-week observation period
      patients received alpha 2a interferon, 3 mega units sc tiw or placebo for 24
      weeks, then the opposite treatment for another 24 weeks followed by 24 weeks of
      observation. Liver biopsies were performed before and after each of the treatment
      phases. Twenty-two out of 24 patients completed the study. The mean alanine
      aminotransferase (ALT) levels fell from 150.7 +/- 118.7 units/l to 91.0 +/- 42.6
      units/l after 6 months interferon treatment (P = 0.03) but only 3 patients (14%)
      had complete normalization of mean ALT levels and 4 (18%) had > 50% reduction.
      The mean hepatitis activity index fell from 12.2 +/- 2.6 immediately before to
      11.6 +/- 2.5 just after interferon (P = 0.4). After interferon there was an
      insignificant raise in 6-month mean ALT. Hepatitis C virus-RNA was positive in
      all 17 patients tested and remained so after treatment. Side-effects were mild
      and well tolerated. Alpha interferon 3 mega units tiw for 24 weeks is not an
      effective treatment of histologically advanced chronic hepatitis C.

PMID- 7512113
TI  - Wavelength-specific upregulation of keratin mRNA expression in response to
      ultraviolet radiation.
AB  - Keratin intermediate filaments are heteropolymers of coexpressed type I and type
      II protein chains, whose expression is tightly linked to the differentiation
      status of the keratinocyte. Epidermal basal keratinocytes coexpress keratins K5
      and K14, whereas suprabasal keratinocytes downregulate K5 and K14 and begin to
      coexpress keratins K1 and K10. Using both isotopic and non-isotopic in situ
      hybridization, we have investigated the changes in expression of the messenger
      RNA species encoding the K5/K14 and K1/K10 keratin pairs in response to
      ultraviolet radiation. Here we report that following irradiation, the mRNA
      species encoding both keratin pairs is upregulated in a wavelength-specific
      manner, and that the link between the pattern of keratin mRNA expression and the
      differentiation status of the keratinocyte is disrupted. Forty-eight hours
      following ultraviolet B exposure, the amount of detectable mRNA encoding all four
      keratins studied had increased. Following UVA irradiation, the K1 and K10 signal
      increased to a much lesser extent than following ultraviolet B, whereas no change
      in the amount of mRNA encoding the K5/K14 pair was observed. Only two samples
      were examined following ultraviolet C exposure, but in both, increased K5/K14
      signal, but not suprabasal K1/K10 signal, was observed. We suggest that the
      observations reported here may reflect important qualitative changes involved in
      photoadaptation of the epidermis, and provide further molecular markers of the
      different biological effects of ultraviolet radiation of different wavelengths.

PMID- 7512112
TI  - Elevated plasma levels of a carbohydrate antigen, sialyl Lewis X, in liver
      diseases.
AB  - A carbohydrate antigen, sialyl Lewis X (SLEX), is an inflammation-associated
      liver cell antigen, which is increasingly expressed as histological diagnosis
      progresses. A solid phase radioimmunoassay was developed to determine the plasma
      levels of this substance which were found to be elevated in about 70% of patients
      with liver disease, with no significant differences among disease groups.
      Although the plasma levels of SLEX were not directly correlated with the degree
      of hepatic SLEX expression, the abnormal values were only found in cases with
      hepatic SLEX expression. Cirrhotic patients with and without hepatocellular
      carcinoma had comparable values. Plasma levels of SLEX decreased significantly in
      chronic hepatitis patients successfully treated with IFN, but not in those
      without a favourable clinical response. Plasma SLEX was carried by some
      macromolecules with chromatographic and buoyant properties of mucin-type
      glycoproteins, and others of non-mucin type. These observations suggested that
      (i) the plasma levels of SLEX increase significantly but non-specifically in
      liver diseases, (ii) liver cells in the inflammatory lesion are probably the
      origin of the SLEX-active glycoproteins in the peripheral circulation, (iii) both
      the increased hepatic synthesis and impaired secretion of the SLEX-positive
      glycoproteins might be related to the tissue expression and plasma levels of
      SLEX, and (iv) plasma SLEX might be a useful marker to evaluate the activity of
      inflammatory liver disease in individual patients and to monitor their treatment.

PMID- 7512114
TI  - A factor in human plasma permits persistent expression of E-selectin by human
      endothelial cells.
AB  - E-selectin is an inducible endothelial cell adhesion protein that is a critical
      element in the binding of leukocytes to activated endothelial cells. It is
      induced by a variety of pro-inflammatory soluble substances including interleukin
      1 (IL-1), tumor necrosis factor (TNF), or bacterial lipopolysaccharide (LPS). In
      vitro studies of a large vessel endothelial cells demonstrate that stimulation
      with TNF or IL-1 leads to a rapid, but transient, induction of E-selectin
      expression that disappears within 24 hours. However, in vivo studies have shown
      that microvascular endothelial cells persistently express E-selectin in chronic
      inflammatory states, particularly in the skin where it serves as a homing
      receptor for memory T cells. Stimulation of dermal-derived microvascular
      endothelial cells (HDMECs) with single doses of IL-1 alpha, TNF alpha, or LPS
      resulted in transient but slightly more persistent expression of E-selectin than
      seen after stimulation of large vessel derived umbilical vein endothelial cells
      (HUVECs). However, stimulation of either HDMECs or HUVECs with repetitive doses
      of IL-1 alpha, TNF alpha, or LPS in the presence of human serum or plasma
      resulted in persistent E-selectin expression in vitro. The persistent E-selectin
      cell surface expression was associated with persistent E-selectin mRNA expression
      and correlated with E-selectin-mediated HL-60 binding to endothelial cell
      monolayers. The effect of human plasma or serum was dose dependent, and
      fractionation of human plasma by gel filtration demonstrated that the E-selectin
      persistence activity resolved into high and low molecular peaks. These data
      demonstrate that human endothelial cells are capable of persistent E-selectin
      expression in vitro and that factors in human serum or plasma are critical in
      preventing cytokine refractoriness and loss of E-selectin expression. This study
      provides a basis to resolve the apparent discrepancies between previous in vivo
      and in vitro dynamics of E-selectin expression.

PMID- 7512115
TI  - Does the gender difference in interferon production seen in picornavirus-infected
      spleen cell cultures from ICR Swiss mice have any in vivo significance?
AB  - Splenocyte cultures from female ICR Swiss mice produced greater interferon (IFN)
      levels, particularly IFN-gamma, than did cultures from males by 12 h post
      infection (pi) with the D variant of encephalomyocarditis virus (EMCV-D). This
      early IFN-gamma is produced by natural killer (NK)-like cells and is dependent on
      plastic adherent cells and IFN-alpha/beta. In this study, we evaluated the
      significance of this observation on the innate resistance of ICR Swiss females to
      EMCV-D-mediated disease. Treatment of females with rabbit anti-mouse IFN
      alpha/beta serum rendered them susceptible to the diabetogenicity of EMCV-D.
      Although sera from both sexes of ICR Swiss mice exhibited peak IFN levels day 3
      pi, IFN-gamma was present in the sera of males at only 1 day pi and in the sera
      of females at days 1-3 pi. Females cleared virus from the circulation by day 2
      pi, 1 day earlier than did males. Flow cytometric evaluations of lymphoid cell
      phenotypes in spleens and pancreata of infected mice revealed that percentages of
      L3T4+ cells were significantly decreased only in spleens from males at day 1 pi
      and were diminished along with Ly2+ cells in pancreata of males at 7 days pi,
      suggesting that T-cell responses were impaired in virus-infected males.

PMID- 7512116
TI  - Lack of expression of intercellular adhesion molecule ICAM-1 in lepromatous
      leprosy patients.
AB  - It is conceivable that an abnormal expression of cell-adhesion molecules can
      contribute to the poor inflammatory response seen in some inflammatory skin
      diseases. Adhesins are cell-surface molecules that are expressed by many cell
      types. The main function of adhesins appears to be the promotion of cellular
      interactions, such as those occurring between immune cells. The epidermis of
      patients with inflammatory skin diseases exhibits an increased expression of ICAM
      1, and it has been postulated that such increased expression can be important in
      the genesis of cutaneous inflammation. The expression of cell-adhesion molecules
      (LFA-1, LFA-2, LFA-3 and ICAM-1) in skin lesions of leprosy patients was studied,
      as well as the in vitro expression of these molecules induced with gamma
      interferon (IFN-gamma). A lack of expression of ICAM-1 in the epidermis of
      lepromatous patients was noted; in addition, no expression of ICAM-1 was seen in
      the nearly normal skin from these patients incubated with IFN-gamma. A similar
      expression of the four molecules studies was noted in the dermis of both the
      lepromatous and tuberculoid types of leprosy. The epidermis of the lepromatous
      leprosy patients appears to have a defective expression of ICAM-1.

PMID- 7512117
TI  - Localization of a functional site on herpes simplex virus type 1 glycoprotein C
      involved in binding to cell surface heparan sulphate.
AB  - The amino acid residues critical for interaction between herpes simplex virus
      type 1 (HSV-1) glycoprotein C (gC-1) and cell surface heparan sulphate (HS) were
      localized to two separate regions within antigenic site II of this glycoprotein.
      These amino acids were Arg-143, Arg-145, Arg-147 and Thr-150 in one region and
      Gly-247 in the other. This conclusion is based on the following observations. (i)
      Monoclonal antibodies defining gC-1 antigenic site II, and not those reactive
      with antigenic site I, inhibited HSV-1-induced haemagglutination and virus
      binding to susceptible cells. (ii) A number of HSV-1 mar mutants, altered at
      these critical residues, were impaired in attachment to cells. (iii) Synthetic
      peptides, corresponding to these two regions inhibited virus attachment to cells
      and infectivity. In addition these peptides were found to agglutinate red blood
      cells. This agglutination was inhibited by soluble HS, and was prevented by the
      pretreatment of red blood cells with heparitinase suggesting that cell surface HS
      was a site of peptide binding. The same was observed with the polycationic
      substances neomycin and poly-L-lysine. In conclusion, we propose that the regions
      of gC-1 represented by the HS-binding peptides may form a functional site of a
      polycationic nature, active in attachment to the polyanionic glycosaminoglycan
      chain of cell surface HS.

PMID- 7512118
TI  - Precipitation of the Epstein-Barr virus protein EBNA 2 by an EBNA 3c-specific
      monoclonal antibody.
AB  - Two monoclonal antibodies, E3cD8 and E3cA10, were generated to the EBNA 3c
      nuclear protein from the B95.8 isolate of Epstein-Barr virus (EBV). Both
      antibodies efficiently precipitate EBNA 3c from B95.8-transformed lymphoblastoid
      cell lines, and E3cA10 also detects EBNA 3c on Western blots. Whereas E3cD8
      reacts with all 11 Type-1 isolates of EBV tested, and E3cA10 reacts with 14 of 17
      Type-1 isolates, neither antibody detects the EBNA 3c protein encoded by Type-2
      isolates. E3cD8 recognizes a peptide sequence (PA/PPQAPYQGY) in a repeat region
      of the B95.8 EBNA 3c coding sequence which is not present in the prototype Type-2
      AG876 sequence. The E3cA10 antibody epitope has been mapped to the minimal five
      amino acid B95.8 peptide, WAPSV, which has an alanine to valine substitution in
      the AG876 virus isolate. This substitution was also found in three Type-1 EBV
      isolates that expressed EBNA 3c proteins not detected by E3cA10. In
      immunoprecipitation studies E3cA10 additionally coprecipitated the EBNA 2 protein
      from Type-1 isolates of EBV. The possibility of a direct interaction between EBNA
      2 and EBNA 3c was ruled out by the demonstration that the antibody precipitated
      EBNA 2 from the Raji cell line which carries a virus with a deleted EBNA 3c gene.
      Since the WAPSV epitope identified in EBNA 3c is not present in EBNA 2, and no
      EBNA 2 linear peptide reactivity was detected in ELISA, it seems likely that
      E3cA10 recognizes a conformational epitope on EBNA 2. However, from the present
      data we cannot exclude the possibility that the antibody reacts with a cellular
      protein that physically associates with EBNA 2.

PMID- 7512120
TI  - Molecular cloning and characterization of a murine AIDS virus-related endogenous
      transcript expressed in C57BL/6 mice.
AB  - The murine AIDS (MAIDS) virus has a unique sequence in the gag p12 region, which
      could be responsible for MAIDS development. RNA preparations from the spleens of
      normal uninfected C57BL/6 mice contain a transcript hybridizing with this
      sequence. Levels of the transcript in the kidney of C57BL/6 mice were higher than
      in the spleen, liver or thymus. Although BALB/c, NFS, DBA/2 and SL murine strains
      also contained genomic sequences hybridizing with the MAIDS virus-specific probe,
      no transcript hybridizing with the probe was detected in these strains of mice.
      The cDNAs carrying the transcript expressed in C57BL/6 mice were molecularly
      cloned. The complete nucleotide sequence of the clone indicates that the
      transcript is one of the endogenous murine leukaemia virus-related sequences
      containing large deletions from the R and U5 regions of the 5' long terminal
      repeat (LTR) to gag p15, from the C-terminal region of pol p40 (integrase) to the
      N-terminal region of env p15E, and many short deletions in the 3' LTR U3 region.
      The nucleotide sequence in the gag p12 region of the transcript was closely
      similar to that of the MAIDS virus, but the amino acid sequence was less similar
      because of frameshifting, even when translated. As the MAIDS virus was isolated
      from C57BL/6 mice with radiation-induced leukaemia, this transcript may be the
      progenitor of the MAIDS virus. To determine whether the gag p12 region of the
      transcript contains a functional sequence, a recombinant virus was generated by
      replacing the gag p12 region of a replication-competent BM5eco virus with that of
      the endogenous transcript. The recombinant virus was replication-competent, and
      the p12 region of the transcript retained the functional sequence present in the
      BM5eco virus.

PMID- 7512119
TI  - Phagocytosis of Mycobacterium tuberculosis modulates human immunodeficiency virus
      replication in human monocytic cells.
AB  - Macrophage activation resulting from phagocytosis has the potential to modulate
      human immunodeficiency virus (HIV) replication. We have determined the effects of
      phagocytosis of particulate stimuli on transcription and release of HIV. Using
      THP-1 and Mono Mac 6 human monocytic cell lines transfected with HIV long
      terminal repeat sequence chloramphenicol acetyltransferase (LTR CAT) constructs
      we have demonstrated that phagocytosis of Mycobacterium tuberculosis enhanced HIV
      1 and -2 LTR CAT expression. However phagocytosis of zymosan or inert latex beads
      had little or no effect on CAT expression. Enhancement of HIV LTR CAT expression
      was dependent upon intact NF-kappa B binding sites and was independent of tumour
      necrosis factor alpha secretion. M. tuberculosis strains of different degrees of
      virulence induced similar levels of enhanced CAT expression. In contrast,
      phagocytosis of M. tuberculosis by HIV-1-infected THP-1 cells reduced supernatant
      reverse transcriptase (RT) activity without suppression of p24 antigen release.
      Phagocytosis of zymosan granules or latex particles did not alter released RT
      activity. However, phagocytosis of either M. tuberculosis, zymosan granules or
      latex particles by HIV-1-infected human peripheral blood monocyte-derived
      macrophages reduced supernatant RT activity. These data indicate that
      phagocytosis of M. tuberculosis may enhance HIV transcription in monocytic cells
      although it may reduce release of intact HIV.

PMID- 7512122
TI  - Determination of the 5' end of the lactate dehydrogenase-elevating virus genome
      by two independent approaches.
AB  - We have determined the 5' end of the lactate dehydrogenase-elevating virus (LDV)
      genome (strain LDV-P) using two independent approaches. In one approach,
      methylmercuric hydroxide-denatured genomic RNA was reverse-transcribed using as
      primer an oligonucleotide complementary to the 5' end of open reading frame (ORF)
      1a. The first-strand cDNA was ligated with T4 RNA ligase to an oligonucleotide of
      which the 3' end was blocked. The ligated product was amplified by PCR, cloned
      and sequenced. In the second approach, untreated or decapped genomic RNA was
      ligated between the 3' and 5' ends, reverse-transcribed across the ligation
      junction and the product was amplified by PCR, cloned and sequenced. Both
      approaches yielded the same results, indicating that the 5' leader of LDV-P is
      156 nucleotides long, inclusive of the 5' UAUAACC 3' sequence involved in the
      linkage of the 5' leader to the bodies of the seven subgenomic mRNAs of LDV. The
      5' leader of LDV is about 50 nucleotides shorter than those of the related
      viruses, equine arteritis virus and Lelystad virus, but at least twice as long as
      the leaders of the coronaviruses. The finding that untreated LDV RNA was ligated
      5' to 3' end as efficiently as RNA treated with decapping enzyme suggests that
      genomic LDV RNA may not possess a 5' cap but terminates with 5' phosphoryl-A.

PMID- 7512123
TI  - Common distribution of antigenic determinants and complementation activity on
      matrix proteins of two vesicular stomatitis virus serotypes.
AB  - To compare the antigenic and functional domains of the matrix (M) proteins of
      vesicular stomatitis virus (VSV) serotypes Indiana (VSV-Ind) and New Jersey (VSV
      NJ), deletion mutants and chimeras were cloned in pBSM13 and expressed as in
      frame lacZ fusion proteins in Escherichia coli. Non-cross-reactive monoclonal
      antibodies directed to the two antigenically distinct M proteins were tested by
      Western blot analysis to map three epitopes of VSV-Ind M protein and four
      epitopes of VSV-NJ M protein. Epitope 1 of the VSV-Ind M protein and epitope II
      of the VSV-NJ M protein both mapped to the highly basic N-terminal 34 amino acids
      of each homotypic M protein. Epitopes 2 and 3 of the VSV-Ind M protein and
      epitopes III and IV of the VSV-NJ M protein mapped to a region spanning amino
      acids 35 to 74. Epitope I of the VSV-NJ M protein mapped to a region between
      amino acid 75 and the C terminus. The similarity in location of the serotypically
      unique antigenic determinants of the two M proteins suggested that they may have
      a common functional domain. This hypothesis was substantiated by the finding that
      the two M proteins and various chimeras expressed in CV-1 cells by a recombinant
      vaccinia virus system were able to rescue M gene temperature-sensitive mutants of
      both VSV serotypes.

PMID- 7512121
TI  - Monoclonal antibodies to immunodominant and neutralizing domains of the envelope
      surface protein of feline immunodeficiency virus.
AB  - Hybridomas secreting monoclonal antibodies (MAbs) specific for the surface
      protein (SU) of feline immunodeficiency virus were generated. Four MAbs were
      obtained which could be assigned to two groups based on their neutralization and
      competition behaviour. Using SU protein fragments expressed in Escherichia coli
      the antigenic site recognized by one of the MAbs (2H11) could be mapped to the c
      terminus. The neutralizing MAb 1E1 did not bind to any of the SU protein
      fragments and was directed to a conformational epitope. Binding of the MAb 1E1 to
      native SU protein could be blocked with a rabbit serum raised against the SU3
      fragment (amino acids 361 to 445). These data indicate that at least part of the
      epitope is located on this SU3 domain. In competition experiments most sera of
      naturally infected cats were able to inhibit binding of the MAbs. This shows the
      conserved and immunodominant nature of the epitopes involved.

PMID- 7512124
TI  - Randomized study of growth factors post-peripheral-blood stem-cell transplant:
      neutrophil recovery is improved with modest clinical benefit.
AB  - PURPOSE: To evaluate the clinical value of growth factors (GFs) with peripheral
      blood stem cells (PBSC) collected following mobilization with GFs, we randomized
      patients to receive or not to receive GFs following transplant. PATIENTS AND
      METHODS: Thirty-seven patients were apheresed after receiving the combination of
      granulocyte colony-stimulating factor (G-CSF) with granulocyte-macrophage colony
      stimulating factor (GM-CSF) at doses of 10 micrograms/kg/d and 5 micrograms/kg/d,
      respectively, for 6 days before apheresis and during a median of 4 days of
      collections. One day after the infusion of autologous marrow and PBSC, patients
      were randomly assigned to receive no GFs or a combination of G-CSF (7.5
      micrograms/kg/d) and GM-CSF (2.5 micrograms/kg/d), both as a 2-hour intravenous
      (i.v.) infusion twice per day until the neutrophil count was greater than
      1,500/microL. RESULTS: The median days to recovery to an absolute neutrophil
      count (ANC) of 100/microL (9 v 11.5, P = .0005), 500/microL (10 v 16, P = .0004),
      or 1,000/microL (12 v 21, P = .0008) was shortened with the use of GFs, post-PBSC
      infusion. In addition, the duration of hospitalization was shorter (19 v 21 days,
      P = .0112) in the arm receiving GFs post-PBSC infusion. There was no significant
      difference between the two study arms in the duration of fever, documented septic
      episodes, or RBC or platelet transfusion requirements. CONCLUSION: Despite faster
      neutrophil recovery and shortened duration of hospitalization with GFs
      administered after PBSC transplantation, the measured clinical variables of
      febrile days, septic episodes, and transfusion requirements were similar between
      the study arms. The use of GFs post-PBSC transfusion is associated with a modest
      clinical benefit.

PMID- 7512125
TI  - Use of granulocyte colony-stimulating factor before, during, and after
      fludarabine plus cytarabine induction therapy of newly diagnosed acute
      myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine
      plus cytarabine without granulocyte colony-stimulating factor.
AB  - PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF)
      administered before, during, and after fludarabine plus cytarabine (ara-C; FA)
      chemotherapy affected complete response (CR) rate, infection rate, blood count
      recovery, or survival in patients with newly diagnosed acute myelogenous leukemia
      (AML) or myelodysplastic syndromes (MDS). PATIENTS AND METHODS: A total of 112
      patients with newly diagnosed AML (n = 69) or MDS (n = 43) received G-CSF 400
      micrograms/m2/d 1 day before (presenting WBC count < 50,000/microL) and/or during
      (all patients) fludarabine 30 mg/m2/d and ara-C 2 g/m2/d for 5 days (FLAG). G-CSF
      continued until a CR was achieved. Results were compared with those in 85 newly
      diagnosed patients (54 AML, 31 MDS) previously treated with FA without G-CSF.
      RESULTS: Patients in both groups were relatively old (median age of all patients,
      63 years), and were likely to have prognostically unfavorable cytogenetic
      abnormalities (36% had abnormalities of chromosomes 5 and 7 [-5/-7]). G-CSF
      accelerated recovery to > or = 1,000 neutrophils (P < .0001; median, 34 days for
      FA, 21 days for FLAG), but logistic regression provided no evidence that the CR
      rate was higher with FLAG than with FA (P = .50), with unadjusted CR rates of 63%
      and 53%, respectively. This may reflect relatively high rates of death before
      neutrophil recovery in both groups. Rates of infection were similar in both
      groups. The follow-up duration in remission is short, and much of these data
      remain censored. To date, survival is similar with FA and FLAG. CONCLUSION: On
      average, G-CSF before, during, and after FA had no effect on CR or infection
      rates in this population, in which elderly patients and poor prognostic factors
      were prevalent. The use of FA and laminar airflow rooms rather than more usual
      therapy needs to be considered when analyzing the results.

PMID- 7512126
TI  - Phase II study of ketoconazole combined with weekly doxorubicin in patients with
      androgen-independent prostate cancer.
AB  - PURPOSE: A phase II clinical trial was performed to assess the antitumor activity
      and toxicity of ketoconazole in combination with doxorubicin (Adriamycin; Adria
      Laboratories, Columbus, OH) in patients with androgen-independent prostate cancer
      (AI PCa). PATIENTS AND METHODS: Thirty-nine consecutive patients whose disease
      progressed following castration were treated with oral ketoconazole (1,200 mg)
      daily and Adriamycin (20 mg/m2 in a 24-hour infusion) once weekly. Antitumor
      activity was assessed by the level of prostatic-specific antigen (PSA) decline.
      RESULTS: PSA levels decreased > or = 50% from baseline in 21 (55%; 95% confidence
      interval, 38% to 71%) of 38 assessable patients. We observed partial responses
      (PRs) in seven (58%) of 12 patients with measurable soft tissue disease (in the
      lung, lymph nodes, and liver). Two patients with history of atherosclerotic heart
      disease had a sudden cardiac death. Serious toxic reactions included grade III to
      V stomatitis and grade III to IV acral erythema in 11 patients (29%), and grade
      III to IV anal and urethral mucositis in five patients (13%). Grade III to IV
      neutropenia occurred in 11 patients (29%). Seventeen patients (45%) required
      hospitalization for complications. Fifteen patients (39%) developed hypokalemia,
      and 24 patients (63%) developed clinical adrenal insufficiency. CONCLUSION: The
      combination of ketoconazole and Adriamycin has a 55% PSA response rate in
      patients with AI PCa and is worthy of additional study. This treatment results in
      frequent adrenal insufficiency. Therefore, future studies should incorporate
      routine corticosteroid replacement. The cardiac complications caused by this
      combination should be studied further before it is widely used.

PMID- 7512127
TI  - Use of palliative end points to evaluate the effects of mitoxantrone and low-dose
      prednisone in patients with hormonally resistant prostate cancer.
AB  - PURPOSE: This phase II study was designed to assess the effects of mitoxantrone
      with prednisone in patients with metastatic prostate cancer who had progressed on
      hormonal therapy. The methods of assessment included quality-of-life analyses,
      pain indices, analgesic scores, and the National Prostatic Cancer Project (NPCP)
      criteria. PATIENTS AND METHODS: Patients received mitoxantrone 12 mg/m2
      intravenously every 3 weeks plus prednisone 10 mg orally daily. All had a
      castrate serum testosterone and Eastern Cooperation Oncology Group (ECOG)
      performance status < or = 3, and had not received prior chemotherapy. Every 3
      weeks, analgesic intake was scored, and a present pain intensity (PPI) record and
      visual analog scale (VAS) describing pain were collected. Every 6 weeks, the
      European Organization for Research and Treatment of Cancer (EORTC) core quality
      of-life questionnaire plus a prostate-specific module were completed. A
      palliative response was defined as a decrease in analgesic score by > or = 50% or
      a decrease in PPI by > or = two integers without any increase in the other.
      RESULTS: Twenty-seven patients were entered onto the study. Nine of 25 (36%)
      assessable patients achieved a palliative response maintained for > or = two
      cycles (range, two to eight or more). Improvements in mean PPI and VAS pain
      scores after each cycle of therapy (P < .05) were seen. Quality-of-life analysis
      showed improvements in social and emotional functioning, and in pain and
      anorexia. Using NPCP criteria, one patient achieved a partial response (PR) and
      12 had stable disease; one of seven patients with measurable disease had a PR. No
      serious nonhematologic toxicity was experienced, and there were no episodes of
      febrile neutropenia. CONCLUSION: Mitoxantrone with low-dose prednisone is a well
      tolerated treatment regimen that has some beneficial effects on disease-related
      symptoms and quality of life for patients with advanced prostate cancer.

PMID- 7512128
TI  - Trial of sequential trimetrexate, fluorouracil, and high-dose leucovorin in
      previously treated patients with gastrointestinal carcinoma.
AB  - PURPOSE: Trimetrexate (TMTX) is a dihydrofolate reductase inhibitor, which, like
      methotrexate (MTX), has been shown to potentiate fluorouracil (FU) cytotoxicity
      by increasing phosphoribosylpyrophosphate (PRPP) levels. We investigated the
      safety and efficacy of a sequential TMTX/FU/leucovorin (LV) combination. PATIENTS
      AND METHODS: Forty-one patients with advanced gastrointestinal carcinoma (mostly
      colorectal) received variable doses of TMTX followed 24 hours later by FU/LV (500
      mg/m2 of each drug). Almost all patients had received previous chemotherapy. The
      initial 19 patients were treated on a 3-week-on/1-week-off schedule without any
      significant toxicity; the remaining patients were treated for 6 consecutive weeks
      followed by a 2-week rest period. TMTX was escalated in 30-mg/m2 increments from
      20 to 110 mg/m2 in separate patient cohorts. When the 110-mg/m2 dose of TMTX was
      reached, the FU dose was escalated from 500 mg/m2 to 600 mg/m2. RESULTS: The
      partial response (PR) rate in assessable patients with colorectal cancer (all
      previously treated) was 20% (seven of 35; 95% confidence interval, 7% to 33%),
      and with other gastrointestinal cancers was one of four patients. Median survival
      has not been reached with a median follow-up of 13.5 months. The maximum
      tolerated dose (MTD) was 110 mg/m2 for TMTX, 500 mg/m2 for FU, and 500 mg/m2 for
      LV on a 6-weeks-on/2-weeks-off cycle. The principal toxicities were grade 3 or 4
      diarrhea, which occurred in 17% of patients, and hypersensitivity reactions,
      which occurred in 26% of patients. CONCLUSION: TMTX can be administered at
      maximal doses in combination with FU and LV without increasing toxicity. The PR
      rate of 20% in advanced colorectal carcinoma patients previously treated with
      chemotherapy is encouraging and merits further study.

PMID- 7512129
TI  - Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and
      bleomycin: a trial of the Gynecologic Oncology Group.
AB  - PURPOSE: This study was performed to determine the effectiveness of postoperative
      adjuvant chemotherapy in patients with surgically resected ovarian germ cell
      tumors. PATIENTS AND METHODS: After tumor removal and thorough surgical staging,
      patients were enrolled on this study and treated with three courses of cisplatin,
      etoposide, and bleomycin (BEP). Reassessment laparotomy was required of
      consenting, appropriate patients initially, but became an optional procedure in
      1989. RESULTS: Of 93 patients assessable on this trial, 89 are continuously free
      of germ cell cancer. At second-look laparotomy, two other patients were found to
      have small foci of immature teratoma; both remain clinically free of recurrence.
      One received subsequent alternate chemotherapy and one did not. Thus, 91 of 93
      patients are currently free of germ cell cancer. Follow-up duration ranges from
      4.0 to 90.3 months, with 67 patients monitored for longer than 2 years. Acute
      toxicity was moderate. One patient developed acute myelomonocytic leukemia 22
      months after diagnosis. Another patient was noted to have a malignant lymphoma 69
      months after protocol treatment. CONCLUSION: Three courses of BEP will nearly
      always prevent recurrence in well-staged patients with completely resected
      ovarian germ cell tumors and should be given to all such patients. The
      development of acute leukemia as a complication of treatment is disturbing and
      mandates careful long-term follow-up, but is unusual and does not alter the risk
      to-benefit ratio of treatment.

PMID- 7512130
TI  - Specific detection of carcinoembryonic antigen-expressing tumor cells in bone
      marrow aspirates by polymerase chain reaction.
AB  - PURPOSE: To establish a sensitive assay for the specific detection of
      carcinoembryonic antigen (CEA)-expressing tumor cells in the bone marrow of
      patients with colorectal cancer and other CEA-positive carcinomas. PATIENTS AND
      METHODS: A CEA-specific nested reverse transcriptase (RT) polymerase chain
      reaction (PCR) assay was developed and optimized using limiting dilutions of a
      CEA-positive cancer cell line mixed with normal bone marrow cell specimens. The
      optimized test was then used to examine bone marrow samples obtained from 15
      patients with abdominal carcinomas (colorectal, n = 10; pancreatic, n = 3;
      gastric, n = 2) and six patients with breast cancer. Specificity was assessed by
      examination of 56 negative controls (malignant hematologic disease, n = 28;
      nonmalignant disease conditions, n = 5; healthy bone marrow donors, n = 8; normal
      peripheral-blood samples, n = 15). For 11 patients with abdominal carcinomas,
      immunostaining evaluations were performed using an anti-CEA and an
      anticytokeratin antibody, and the results compared with the nested PCR assay.
      RESULTS: In the sensitivity calibration system, single CEA-expressing tumor cells
      were detected in 2 to 5 x 10(7) normal bone marrow cells. All 56 control samples
      failed to amplify. This demonstrates that mRNAs coding for highly homologous CEA
      related antigens expressed by various lineages of blood cells do not interfere.
      Bone marrow samples from 10 of 15 patients with abdominal cancers and four of six
      breast cancer patients scored positive, indicating micrometastatic bone disease.
      Four of 11 samples from the gastrointestinal cancer patients were found to be
      positive by the PCR method, but were negative with the immunocytology method.
      CONCLUSION: Since approximately 30% of the colorectal carcinoma patients that
      score negative in immunocytology staining of bone marrow samples have been
      reported to relapse, earlier diagnosis of the presence of malignant cells is
      needed. Our result that samples scoring positive in the described CEA-specific
      PCR test remained negative by two immunostaining methods suggests a higher
      sensitivity. We conclude that PCR amplification of CEA mRNA may lead to an
      earlier diagnosis of micrometastatic bone disease in patients with CEA-expressing
      carcinomas.

PMID- 7512131
TI  - Randomized comparison of MACOP-B with CHOP in patients with intermediate-grade
      non-Hodgkin's lymphoma. The Australian and New Zealand Lymphoma Group.
AB  - PURPOSE: To compare complete response rates, time to failure, survival, and
      toxicity for patients with intermediate-grade non-Hodgkin's lymphoma (NHL)
      treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)
      versus those treated with a regimen consisting of methotrexate, doxorubicin,
      cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP-B), in a
      multicenter, randomized controlled trial performed by 22 centers of the
      Australian and New Zealand Lymphoma Group (ANZLG). PATIENTS AND METHODS: Between
      October 1986 and June 1991, 304 patients were randomized, of whom 236 were
      eligible for analysis. Eligibility criteria included diffuse small cleaved-cell,
      diffuse mixed small- and large-cell, follicular large-cell, diffuse large-cell,
      and large-cell immunoblastic, stages I bulky or II to IV. RESULTS: There was no
      significant difference in complete response rates (51% for MACOP-B v 59% for
      CHOP), failure-free survival, or overall survival in the two treatment arms. The
      rate of death of MACOP-B patients relative to CHOP patients was estimated to be
      0.91 (P = .64) when stratified by prognostic group. There were no significant
      differences between the two regimens in any of the prognostic subgroups. Toxicity
      was significantly more severe with MACOP-B, particularly cutaneous toxicity,
      stomatitis, and gastrointestinal ulceration. The average relative dose-intensity
      (RDI) of MACOP-B was 0.91 and of CHOP was 0.90, indicating good dose delivery in
      this multicenter group setting. CONCLUSION: CHOP chemotherapy produced results
      equivalent to those of MACOP-B in patients with intermediate-grade NHL and with
      significantly fewer toxic complications. Despite relatively poor results in some
      patient subgroups, CHOP remains the standard chemotherapy for this disease,
      against which all new regimens should be compared.

PMID- 7512132
TI  - ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central
      Lymphoma Group.
AB  - PURPOSE: The United Kingdom Central Lymphoma Group (CLG) has modified
      mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin,
      bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) by substituting
      mechlorethamine with chlorambucil and dacarbazine with etoposide in the treatment
      of patients with advanced Hodgkin's disease (HD). Prednisolone is included in the
      bleomycin-containing combination, and the vinca alkaloids have been switched to
      balance the myelotoxicity of the two component regimens. PATIENTS AND METHODS:
      The resulting ChlVPP/PABlOE regimen is as follows: on days 1 to 14, chlorambucil
      6 mg/m2 orally, procarbazine 100 mg/m2 orally, and prednisolone 30 mg/m2 orally;
      on days 1 and 8, vinblastine 6 mg/m2 intravenously (i.v.); on day 29, doxorubicin
      40 mg/m2 i.v.; on days 29 and 36, vincristine 1.4 mg/m2 (maximum, 2 mg) i.v., and
      bleomycin 10 mg/m2 i.v.; on days 30, 31, and 32, etoposide 200 mg/m2/d orally; on
      days 29 to 43, inclusive, prednisolone, 30 mg/m2 orally. The second full cycle
      restarts on day 50. Treatment continues to maximum response plus two full cycles,
      but with a minimum of three full cycles. Radiotherapy is administered, after
      chemotherapy, to sites of previously bulky disease. Since 1983, 216 patients with
      previously untreated, advanced Hodgkin's disease (HD) have entered this study.
      RESULTS: The complete remission (CR) rate after chemotherapy was 73% (95%
      confidence interval [CI], 67% to 79%), and after additional radiotherapy was 85%
      (95% CI, 80% to 90%). The failure-free survival (FFS) rate at 5 years was 68%
      (95% CI, 61% to 74%), and the overall actuarial survival at 5 years was 78% (95%
      CI, 72% to 84%). The CR rate in patients in the poorer prognostic categories was
      high: 81% in patients with albumin levels less than 37 g/L, 79% in patients older
      than 40 years of age, 84% in stages IIIB plus i.v. disease, and 79% in patients
      presenting with B symptoms. As expected, nausea and vomiting were not major
      problems, although infection, often in the context of myelosuppression,
      complicated almost half the cases, and 29% of patients required admission at some
      stage for treatment of infection. CONCLUSION: In this multicenter study,
      ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but
      with less nausea and vomiting. Treatment duration was shorter than in the
      original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B
      (CALGB) trial. It will now be compared with PABlOE alone.

PMID- 7512133
TI  - Prospering through professionalism.
AB  - An ADA study commissioned in 1989 and published in 1991 revealed public attitudes
      toward dental professionals. This paper suggests asking dental professionals
      about some of their attitudes toward dentistry. Personal prosperity or
      fulfillment, as well as professional prosperity, is possible in the dental
      profession and can be achieved by pursuing a variety of strategies.

PMID- 7512134
TI  - A business approach to dental practice.
AB  - While the approach to dental practice has changed through the decades, the
      characteristics of a successful practice remain constant. This article presents
      some of those characteristics, as well as means of achieving them.

PMID- 7512137
TI  - [Is "symptomatic benign hypertrophy" of the prostate linked to prostatic
      hypertrophy?].

PMID- 7512136
TI  - Antifungal agents and modern antifungal therapy in dentistry.

PMID- 7512139
TI  - [Mesenteric lymph node cavitations in Whipple's disease. Apropos of a case].
AB  - We report a computed tomographic and echographic description of lymphadenopathy
      during a Whipple's disease. The computed tomography find low density of involved
      lymph nodes because of the high fatty charge, ultrasound revealed diffusely
      echogenic aspect. This cavitation was highly suggestive of Whipple's disease.
      Moreover, the computed tomography allows the follow-up of the disease.

PMID- 7512138
TI  - [TULIP: transurethral ultrasound-guided laser-induced prostatectomy. One-year
      clinical results].
AB  - The TULIP (transurethral ultrasound-guided laser-induced prostatectomy) system
      combines a real-time ultrasound transducer and a Nd:YAG laser delivery system
      with a 1.064 microns wavelength within a 22 F urethral probe. The goal is to
      produce a coagulation necrosis of the prostatic parenchyma, with a subsequent
      elimination of tissue in the urine. 29 patients have been included in this study,
      and 13 have a minimal one year follow-up. No complication occurred. 2 patients
      underwent a transurethral resection of the prostate secondary to the TULIP
      treatment. All patients complained of irritative urinary symptoms (frequency,
      burning on urination...) in the days or weeks following the treatment, and
      suprapubic catheterization tube had to be left in place for a mean duration of
      13.8 days. Inclusion/exclusion criteria and evaluation modalities have been the
      same as in the American national study published elsewhere. At one year, our
      success rate for at least one criteria has been 84.6%, but only 2 (15%) out of 13
      patients have been successful both in symptom score and flow rate.

PMID- 7512135
TI  - Pain and anxiety control in dentistry.
AB  - The management of pain and anxiety form the backbone of contemporary dental
      practice. The past decades have seen the introduction of a significant number of
      promising new techniques, drugs and equipment designed to aid the dental
      professional in the quest for a more pain-free and fear-free dental practice.
      This paper presents a brief look at these drugs and techniques.

PMID- 7512140
TI  - Resolution, absolute stereochemistry, and pharmacology of the S-(+)- and R-(-)
      isomers of the apparent partial AMPA receptor agonist (R,S)-2-amino-3-(3-hydroxy
      5-phenylisoxazol-4-yl)propionic acid [(R,S)-APPA].
AB  - (R,S)-2-Amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid ((R,S)-APPA) is
      the only partial agonist at the (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4
      yl)propionic acid (AMPA) subtype of excitatory amino acid receptors so far
      described. In light of the pharmacological interest in partial agonists, we have
      now accomplished the resolution of (R,S)-APPA. (S)-(+)-APPA (5) and (R)-(-)-APPA
      (6) were obtained in high enantiomeric purity using (R)-(+)- and (S)-(-)-1
      phenylethylamine, respectively, as resolving agents. The absolute stereochemistry
      of 6 was established by X-ray analysis of 6.HCl.0.25H2O. Compounds 5 and 6 were
      tested electropharmacologically using the rat cortical wedge preparation and in
      receptor-binding assays using [3H]-AMPA, [3H]kainic acid, and the N-methyl-D
      aspartic acid (NMDA) receptor ligands [3H]CPP, [3H]MK-801, and [3H]glycine.
      Whereas 6 did not significantly affect the binding of any of these ligands (IC50
      > 100 microM), compound 5 revealed affinity for only the [3H]AMPA-binding site
      (IC50 = 6 microM). In electropharmacological tests, 5 showed full AMPA receptor
      agonism (EC50 = 230 microM). This effect of 5 was insensitive to the NMDA
      antagonist CPP but was inhibited competitively by the non-NMDA antagonist NBQX
      (pKi = 6.30). Compound 6, on the other hand, turned out to be a non-NMDA receptor
      antagonist, inhibiting competitively depolarizations induced by AMPA (pKi =
      3.54), kainic acid (pKi = 3.07), and 5 (pKi = 3.57).

PMID- 7512141
TI  - Synthesis of L-thiocitrulline, L-homothiocitrulline, and S-methyl-L
      thiocitrulline: a new class of potent nitric oxide synthase inhibitors.
AB  - Nitric oxide synthase catalyzes the NADPH- and O2-dependent conversion of L
      arginine to L-citrulline and nitric oxide. L-Thiocitrulline, L
      homothiocitrulline, and S-methyl-L-thiocitrulline, novel citrulline analogs, have
      been synthesized and are shown to be potent inhibitors of both the constitutive
      brain and the inducible smooth muscle isoforms of nitric oxide synthase. Although
      many N omega-monosubstituted arginine derivatives inhibit nitric oxide synthase,
      inhibitory citrulline derivatives have not previously been reported. S-Methyl-L
      thiocitrulline is significantly more potent than N omega-methyl-L-arginine, the
      prototypic nitric oxide synthase inhibitor.

PMID- 7512142
TI  - Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines. 1. A novel
      class of non-nucleoside HIV-1 reverse transcriptase inhibitors.
AB  - A variety of analogues of 1-[4-methoxy-3,5-dimethylbenzyl]-4-[3-(ethylamino)-2
      pyridyl]piperazine hydrochloride (U-80493E) were synthesized and evaluated for
      their inhibition of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT). Replacement of the substituted aryl moiety with various
      substituted indoles provided bis(heteroaryl)piperazines (BHAPs) that were 10-100
      fold more potent than U-80493E. The pyridyl portion of the lead molecule was
      found to be very sensitive to modifications. Extensive preclinical evaluations of
      several of these compounds led to the selection of 1-[(5-methoxyindol-2
      yl)carbonyl]-4-[3-(ethylamino)-2- pyridyl]piperazine methanesulfonate (U-87201E,
      atevirdine mesylate) for clinical evaluation.

PMID- 7512143
TI  - Acute lindane intoxication: a study on lindane tissue concentration and oxidative
      stress-related parameters in liver and erythrocytes.
AB  - Treatment of rats with daily doses of 20 mg of lindane/kg for 3 consecutive days
      led to the accumulation of the insecticide in several tissues, including
      erythrocytes and liver. Lindane did not alter the hematocrit and hemoglobin
      concentration but reduced methemoglobin levels by 17%. Red blood cells from
      controls and lindane-treated rats, exposed to t-butyl hydroperoxide, exhibited
      comparable rates of oxygen uptake and visible chemiluminescence, whereas the
      induction period that precedes oxygen uptake was significantly enhanced in the
      latter group. Lindane treatment did not modify the activity of erythrocyte
      glutathione peroxidase, glucose-6-phosphate dehydrogenase, catalase, and
      methemoglobin reductase, being the total content of glutathione and superoxide
      dismutase activity significantly increased. The liver from lindane-treated rats
      showed an enhanced microsomal pro-oxidant activity, evidenced by higher
      cytochrome P450 content and NADPH-cytochrome c reductase and NADPH oxidase
      activities. The higher enzyme activities led to an increased superoxide anion
      generation (adrenochrome formation) and lipid peroxidation (measured either by
      the production of thiobarbituric acid reactants and spontaneous visible
      chemiluminescence). Concomitantly, liver glutathione content and the activity of
      glutathione peroxidase-glutathione reductase couple were augmented by lindane
      treatment, without any change in superoxide dismutase activity, together with a
      reduction in that of catalase. Results suggest that lindane does not alter the
      prooxidant/antioxidant status of the erythrocyte in conditions of a significant
      cellular accumulation of the insecticide, which might exert direct action on
      enzymatic systems leading to enhanced superoxide dismutase activity and
      glutathione content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512146
TI  - Cutis laxa: a feature of Costello syndrome.

PMID- 7512145
TI  - Severe pulmonary and digestive disease in a cystic fibrosis child homozygous for
      G542X.

PMID- 7512144
TI  - Sotos syndrome: a study of the diagnostic criteria and natural history.
AB  - Seventy-nine patients with a provisional diagnosis of Sotos syndrome were
      clinically assessed, and their photographs between the ages of 1 and 6 years
      evaluated. These photographs, together with photographs of first degree
      relatives, also at ages 1 to 6 years, were reviewed by four clinical geneticists.
      Forty-one probands (but no first degree relatives) were identified in whom the
      facial gestalt was thought to be characteristic of Sotos syndrome. Comparison of
      anthropometric measurements, bone age, and developmental delay in these 41
      probands showed marked differences between them and the remaining 38 probands,
      and allowed the formulation of guidelines for the diagnosis of Sotos syndrome.
      Length was identified as the most significantly increased prenatal parameter. In
      childhood occipitofrontal head circumference (OFC), height, and weight were all
      increased. OFC remained above the 97th centile in all but one case throughout
      childhood and adulthood, whereas height and weight had a tendency to return
      towards the mean. This 'normalisation' was more pronounced in females and was
      probably related to their early puberty. Early developmental delay and an
      advanced bone age, seen in 100% and 84% respectively of study cases, may be
      invariable in Sotos syndrome, but selection bias and limited data prevented
      confirmation of this supposition. The authors suggest that facial gestalt, growth
      pattern, bone age, and developmental delay are the major diagnostic criteria.
      Using these criteria, no affected first degree relatives were identified. There
      were few long term medical complications in the probands, but behavioural
      difficulties caused considerable parental concern.

PMID- 7512147
TI  - Transport proteins and acute phase reactant proteins in children with sickle cell
      anemia.
AB  - Transport proteins, acute-phase reactant proteins (APRP), hematology, and
      anthropometry were studied in 34 sickle cell disease (SCD) children (20 boys, 14
      girls) and 27 controls without growth deficits (13 boys, 14 girls) [corrected].
      The age range was 1/2 to 16 1/2 years. Weight deficits (< 80%) by Waterlow's
      classification were observed in 41% of SCD boys and 25% of SCD girls, and height
      deficits (< 90%) were observed in 25% SCD boys and 25% girls. Mean white blood
      cell counts were significantly higher (P < .001) and hematocrit and hemoglobin
      (Hb) lower (P < .005) in SCD children than in controls. Although both groups had
      similar mean levels of albumin, transferrin, and APRP, SCD children had
      significantly lower mean levels of retinol-binding protein (RBP) (P < .001) and
      retinol-prealbumin (P < .001). Retinol-binding protein levels were abnormal in 18
      (53%) SCD children and in only 23% controls (chi 2 = 14.06; P < 0.005);
      transferrin levels were abnormal in 20% of SCD children and in none of the
      controls. Children with SC and SF Hb phenotype had normal mean levels of RBP,
      whereas those with S beta thal and SS phenotype had levels below normal. Growth
      retarded children by weight and height had reduced mean levels of RBP and
      prealbumin compared with growth-normal SCD children. The implication of primary
      protein-energy malnutrition on growth retardation in SCD children is under study.

PMID- 7512148
TI  - T cell receptor V beta gene usage in the recognition of myelin basic protein by
      cerebrospinal fluid- and blood-derived T cells from patients with multiple
      sclerosis.
AB  - Because of its proximity to the central nervous system, the cerebrospinal fluid
      (CSF) represents an important source of T cells that potentially could mediate
      putative autoimmune diseases such as multiple sclerosis (MS). To overcome the low
      CSF cellularity, we evaluated culture conditions that could expand CSF T cells,
      with a focus on the expression of T-cell receptor V beta genes utilized by T
      cells specific for the potentially encephalitogenic autoantigen myelin basic
      protein (BP). Expansion of "activated" CSF cells with IL-2/IL-4 plus accessory
      cells optimally retained BP-responsive T cells that over-expressed V beta 1, V
      beta 2, V beta 5, or V beta 18, compared to expansion using supernatants from PHA
      stimulated blood cells, or anti-CD3 antibody that led to different V gene bias
      and rare reactivity to BP. Sequential evaluation of paired CSF and blood samples
      from a relapsing remitting MS patient indicated that BP-reactive T cells were
      present in CSF during the period of clinical activity, and the pattern of BP
      recognition in CSF was partially reflected in blood, even after CSF reactivity
      had dissipated during remission. Over-expressed V beta genes were not always
      constant, however, since in three sequential evaluations of a chronic progressive
      MS patient, V beta genes over-expressed in the first BP-reactive CSF switched to
      a different V beta gene bias that was present in the second and third CSF
      samples. Blood samples reflected each pattern of CSF V beta gene bias, but
      retained the initial bias for at least 4 months after its disappearance from CSF.
      These data indicate that selective expansion of IL-2/IL-4-responsive CSF cells
      favors growth of the BP-reactive subpopulation, and, in a limited number of
      patients studied, reflected clinical disease activity. In comparison, blood T
      cells provided a partial but longer lasting reflection of the CSF BP reactivity
      and V beta gene bias.

PMID- 7512149
TI  - Glucocorticoid-induced upregulation of proteolipid protein and myelin-associated
      glycoprotein genes in C6 cells.
AB  - The effect of dexamethasone on the expression of proteolipid protein (PLP) and
      myelin-associated glycoprotein (MAG) genes was investigated in rat C6 glioma
      cells. The steady state level of the respective mRNAs was quantitated by Northern
      blot analysis. The treatment of cells with dexamethasone transiently upregulated
      the expression of both genes with peak mRNA levels of approximately 10-fold over
      control levels occurring at day 3 for the PLP gene and at day 5 for the MAG gene.
      The effect was directly related to the drug concentration in the range from 10(
      9) to 10(-5) M. Combined exposure of the cells to dexamethasone and retinoic acid
      featured an additive effect on PLP gene expression, whereas MAG gene expression
      was depressed below detectability level. The dissimilarity in the response of the
      genes to dexamethasone and retinoic acid supports the contention that the genes
      are controlled by different mechanisms. Furthermore, the results indicate that
      the effects of dexamethasone and retinoic acid on the myelin genes are mediated
      by different regulatory pathways.

PMID- 7512150
TI  - Establishment and application of SPA-co-operated ELISA for detection of anti-HCV
      IgM.
AB  - A staphylococcus aureus protein A co-operated ELISA (SPA-ELISA) for the detection
      of anti-HCV-IgM has been established using HCV antigenic polypeptide, SPA-bearing
      germs and horseradish peroxidase labelled anti-human IgM. The specificity of SPA
      ELISA has been confirmed by some substitution tests, blocking tests and
      destroying test with 2-mercaptoethanol. The results showed that the rate of anti
      HCV-IgG in a group of patients with acute hepatitis and there were significant
      difference in anti-HCV-IgM was higher than that of anti-HCV-IgM detected rates
      between patients with acute hepatitis and those with chronic hepatitis (32.26%, P
      < 0.01). On the other hand, the positive rates of anti-HCV-IgM were 53.66% and
      63.41% in transfusion associated hepatitis, 38.10% and 42.86% in sporadic
      hepatitis, 6.11% and 16.33% in people who have had active social activities,
      40.00% and 10.00% in a group of blood donors respectively. Furthermore, taking
      into account the characteristics of HCV polypeptide used, its easiness of
      manipulation, and elimination of the interference of anti-HCV-IgG in sera, the
      new SPA-ELISA is believed to be of practical value in clinical and
      epidemiological studies of hepatitis C.

PMID- 7512151
TI  - Hepatitis C virus infection in different groups of children in Wuhan area.
AB  - To investigate the incidence of child's HCV infection in our area, 637 children
      with different background, including 65 posttransfusion cases, 419 hepatitis
      patients (250 cases of acute hepatitis A, 156 cases of chronic hepatitis B and 13
      cases of non-A, non-B hepatitis), 50 infantile hepatitis syndrome (IHS) infants
      and 103 healthy day-cared children were tested for serum anti-HCV antibody (EIA)
      and HCV RNA (nested PCR). It was found that posttransfusion children had
      significantly higher anti-HCV positive rate (30.8%) and HCV infection incidence
      (43.1%) than hepatitis patients (4.3% and 5.3%), IHS infants (6.0% and 8.0%) and
      day-cared children (2.9% and 2.9%). 25 of 33 cases with posttransfusion hepatitis
      (PTH) developed hepatitis C, which was the leading cause of PTH (75.8%) and NANB
      PTH (25/30, 83.3%). The incidence of HCV infection in NANBH patients was 23.1%
      (3/13) which was apparently higher than that in day-cared children (P < 0.02) and
      lower than that in PTH patients (P < 0.001), but not statistically different from
      that in AHA and CHB patients (P > 0.05). Mother-infant paired study in IHS group
      showed that 4 pairs of mother-infant had HCV infection, one boy aged 8 months and
      his mother were anti-HCV positive, and another 3 pairs possessed HCV RNA in sera.
      3 of 103 healthy day-cared children were found to have inapparent HCV infection,
      who were anti-HCV and HCV RNA positive.

PMID- 7512153
TI  - Circulating anti-Tax cytotoxic T lymphocytes from human T-cell leukemia virus
      type I-infected people, with and without tropical spastic paraparesis, recognize
      multiple epitopes simultaneously.
AB  - CD8+ T cells were freshly isolated from a human T-cell leukemia virus type I
      (HTLV-I)-infected patient with tropical spastic paraparesis. These cells, which
      were specific for HTLV-I Tax, simultaneously recognized a minimum of five, and
      possibly as many as seven, distinct peptide epitopes within the protein. A
      further Tax epitope was recognized after a short period of culture without
      exogenous peptide stimulation. All but one of these epitopes were clustered in
      the N-terminal third of Tax, and one of the epitopes was clearly immunodominant
      on two separate occasions of testing. Recognition of the immunodominant epitope
      was restricted by human leukocyte antigen (HLA) B15, and recognition of all the
      others was by HLA A2. Similar patterns of cytotoxic T lymphocyte recognition of
      the HLA A2-restricted Tax peptides in two healthy HTLV-I-seropositive
      individuals, each of whom carried the HLA A2 allele, were observed.

PMID- 7512152
TI  - Antigenic specificities of human CD4+ T-cell clones recovered from recurrent
      genital herpes simplex virus type 2 lesions.
AB  - Lesions resulting from recurrent genital herpes simplex virus (HSV) infection are
      characterized by infiltration of CD4+ lymphocytes. We have investigated the
      antigenic specificity of 47 HSV-specific CD4+ T-cell clones recovered from the
      HSV-2 buttock and thigh lesions of five patients. Clones with proliferative
      responses to recombinant truncated glycoprotein B (gB) or gD of HSV-2 or purified
      natural gC of HSV-2 comprised a minority of the total number of HSV-specific
      clones isolated from lesions. The gC2- and gD2-specific CD4+ clones had cytotoxic
      activity. The approximate locations of the HSV-2 genes encoding HSV-2 type
      specific CD4+ antigens have been determined by using HSV-1 x HSV-2 intertypic
      recombinant virus and include the approximate map regions 0.30 to 0.46, 0.59 to
      0.67, 0.67 to 0.73, and 0.82 to 1.0 units. The antigenic specificity of an HLA
      DQ2-restricted, HSV-2 type-specific T-cell clone was mapped to amino acids 425 to
      444 of VP16 of HSV-2 by sequential use of an intertypic recombinant virus
      containing VP16 of HSV-2 in an HSV-1 background, recombinant VP16 fusion
      proteins, and synthetic peptides. Each of the remaining four patients also
      yielded at least one type-specific T-cell clone reactive with an HSV-2 epitope
      mapping to approximately 0.67 to 0.73 map units. The antigenic specificities of
      lesion-derived CD4+ T-cell clones are quite diverse and include at least 10
      epitopes. Human T-cell clones reactive with gC and VP16 are reported here for the
      first time.

PMID- 7512154
TI  - Isoprenylation masks a conformational epitope and enhances trans-dominant
      inhibitory function of the large hepatitis delta antigen.
AB  - Hepatitis delta antigen (HDAg) consists of two species, large (LHDAg) and small
      (SHDAg), which are identical in sequence except that the large form contains 19
      extra amino acids at the C terminus. The large form is prenylated on the Cxxx
      motif. The small form can trans activate HDV RNA replication, while the large
      form inhibits it. To determine the molecular basis for their differential
      functions, we examined the effects of prenylation on the conformation and
      function of HDAg. We show that the presence of prenylates masks a conformational
      epitope which is present in SHDAg but hidden in wild-type LHDAg; this epitope
      becomes exposed in all of the nonprenylated mutant LHDAgs. Prenylation also plays
      a major role in conferring the trans-dominant negative inhibitory activity of
      LHDAg, since the loss of prenylation in LHDAg reduced its inhibitory activity.
      The primary amino acids of the C-terminal sequence also contributed to the
      maintenance of the HDAg protein conformation; a prenylated LHDAg mutant with a
      five-amino-acid deletion had an exposed C-terminal epitope. By examining LHDAg
      mutants which have deletions of various extents of C-terminal sequence, with or
      without the prenylation motif, we have further shown that all of the prenylated
      mutants have much higher levels of trans-dominant suppressor activities than do
      the corresponding nonprenylated mutants. Surprisingly, a few nonprenylated LHDAg
      mutants were able to trans activate HDV RNA replication, while all of the
      prenylated ones lost this function. These results suggest that isoprenylates
      cause the masking of a conformational epitope of HDAg and that conformational
      differences between the large and small HDAgs account for the differences in
      their trans-activating and trans-dominant inhibitory biological activities.

PMID- 7512156
TI  - Characterization of human antibody responses to four corners hantavirus
      infections among patients with hantavirus pulmonary syndrome.
AB  - Hantavirus pulmonary syndrome (HPS) is a human disease caused by a newly
      identified hantavirus, which we will refer to as Four Corners virus (FCV). FCV is
      related most closely to Puumala virus (PUU) and to Prospect Hill virus (PHV).
      Twenty-five acute HPS serum samples were tested for immunoglobulin G (IgG) and
      IgM antibody reactivities to FCV-encoded recombinant proteins in Western blot
      (immunoblot) assays. All HPS serum samples contained both IgG and IgM antibodies
      to the FCV nucleocapsid (N) protein. FCV N antibodies cross-reacted with PUU N
      and PHV N proteins. A dominant FCV N epitope was mapped to the segment between
      amino acids 17 and 59 (QLVTARQKLKDAERAVELDPDDVNKSTLQSRRAAVSALETKLG). All HPS
      serum samples contained IgG antibodies to the FCV glycoprotein-1 (G1) protein,
      and 21 of 25 serum samples contained FCV G1 IgM antibodies. The FCV G1 antibodies
      did not cross-react with PUU G1 and PHV G1 proteins. The FCV G1 type-specific
      antibody reactivity mapped to a segment between amino acids 59 and 89
      (LKIESSCNFDLHVPATTTQKYNQVDWTKKSS). One hundred twenty-eight control serum samples
      were tested for IgG reactivities to the FCV N and G1 proteins. Nine (7.0%)
      contained FCV N reactivities, 3 (2.3%) contained FCV G1 reactivities, and one
      (0.8%) contained both FCV N and FCV G1 reactivities. The epitopes recognized by
      antibodies present in control serum samples were different from the epitopes
      recognized by HPS antibodies, suggesting that the control antibody reactivities
      were unrelated to FCV infections. These reagents constitute a type-specific assay
      for FCV antibodies.

PMID- 7512155
TI  - Hepadnavirus P protein utilizes a tyrosine residue in the TP domain to prime
      reverse transcription.
AB  - Hepadnavirus DNA minus strands are covalently linked at their 5' terminus to the
      viral P gene product, which has been taken to indicate that the hepadnaviral
      polymerase polypeptide itself also functions as a protein primer for initiating
      reverse transcription of the RNA pregenome. The present study confirms this
      indication by identifying the nucleotide-linked amino acid in the P protein
      sequence of the duck hepatitis B virus (DHBV). In a first set of experiments,
      mutational analysis of three phylogenetically conserved tyrosine residues in the
      DNA terminal (TP) domain indicated that of these, only tyrosine 96 was essential
      for both viral DNA synthesis in transfected cells and priming of DNA synthesis in
      a cell-free system. This assignment was confirmed by direct biochemical analysis:
      tryptic peptides from the DHBV P protein, 32P labelled at the priming amino acid
      by the initiating dGTP and additionally labelled internally by [35S]methionine,
      were isolated and analyzed in parallel to reference peptides synthesized
      chemically and 33P labelled by a tyrosine kinase. Mobility in high-performance
      liquid chromatography, as well as the release in stepwise amino acid sequencing
      of phospholabel and of [35S]methionine, identified the priming amino acid
      unequivocally as the tyrosine in the sequence 91KLSGLYQMK99, which is located in
      the center of the TP domain. Conserved sequence motifs surrounding Tyr-96 allow
      the prediction of the priming tyrosine in other hepadnaviruses. Weak sequence
      similarity to picornavirus genome-linked polypeptides (VPgs) and similar gene
      organization suggest a common origin for the mechanisms that use protein priming
      to initiate synthesis of viral DNA genomes or RNA genomes from an RNA template.

PMID- 7512158
TI  - Two subpopulations of human triple-negative thymic cells are susceptible to
      infection by human immunodeficiency virus type 1 in vitro.
AB  - Some infants infected with human immunodeficiency virus type 1 (HIV-1) rapidly
      develop a fatal disease characterized by a severe lymphopenia. To explain the
      immune dysfunction, we proposed a mechanism by which a nongeneration of CD4+ T
      cells is caused by HIV-1 infection of thymic cells. To examine this hypothesis,
      we infected primary triple-negative (TN; phenotypically CD3- CD4- CD8-), CD1a-
      TN, or CD1a+ TN thymic cell subsets. Our data indicate that by flow cytometry,
      TN, CD1a- TN, and CD1a+ TN cells remain CD4 negative throughout the culture
      period. We demonstrated that TN and CD1a+ TN thymic cell subsets are susceptible
      to HIV-1 as is the entire thymic cell population, whereas CD1a- TN cells are not.
      A limited number of infected TN cells are expressing HIV-1 but the level of
      transcription is very high in permissive cells, as detected by in situ
      hybridization. We then performed blocking experiments on TN cells to examine the
      mechanism of HIV-1 entry into these cells. CD4 (OKT4a) monoclonal antibody blocks
      their infection. Finally, infection experiments on two subpopulations of TN cells
      (CD2+ CD7+ and CD2- CD7-) indicate that infected TN cells may correspond to both
      immature thymocytes and thymic dendritic cells. These data are of particular
      interest since infection of thymic stromal cells might result in an impairment of
      T-cell differentiation, which may explain a nongeneration of functional CD4+ T
      cell population in the thymus. This phenomenon may play a role in AIDS
      pathogenesis, in particular in infants born from seropositive mothers.

PMID- 7512157
TI  - Native oligomeric human immunodeficiency virus type 1 envelope glycoprotein
      elicits diverse monoclonal antibody reactivities.
AB  - We synthesized and purified a recombinant human immunodeficiency virus type 1
      (HIV-1) envelope (Env) glycoprotein, lacking the gp120/gp41 cleavage site as well
      as the transmembrane domain, that is secreted principally as a stable oligomer.
      Mice were immunized with separated monomeric and oligomeric HIV-1 Env
      glycoproteins to analyze the repertoire of antibody responses to the tertiary and
      quaternary structure of the protein. Hybridomas were generated and assayed for
      reactivity by immunoprecipitation of nondenatured Env protein. A total of 138
      monoclonal antibodies (MAbs) were generated and cloned, 123 of which were derived
      from seven animals immunized with oligomeric Env. Within this group, a
      significant response was obtained against the gp41 ectodomain; 49 MAbs recognized
      epitopes in gp41, 82% of which were conformational. The influence of conformation
      on gp120 antigenicity was less pronounced, with 40% of the anti-gp120 MAbs
      binding to conformational epitopes, many of which blocked CD4 binding.
      Surprisingly, less than 7% of the MAbs derived from mice immunized with
      oligomeric Env recognized the V3 loop. In addition, MAbs to linear epitopes in
      the C-terminal domain of gp120 were not obtained, suggesting that this region of
      the protein may be partially masked in the oligomeric molecule. A total of 15
      MAbs were obtained from two mice immunized with monomeric Env. Nearly half of
      these recognized the V3 loop, suggesting that this region may be a less
      predominant epitope in the context of oligomeric Env than in monomeric protein.
      Thus, immunization with oligomeric Env generates a large proportion of antibodies
      to conformational epitopes in both gp120 and gp41, many of which may be absent
      from monomeric Env.

PMID- 7512159
TI  - The tat/rev intron of human immunodeficiency virus type 1 is inefficiently
      spliced because of suboptimal signals in the 3' splice site.
AB  - Proportional expression of retroviral genes requires that splicing of the viral
      primary transcript be an inefficient process. Much of our current knowledge about
      retroviral suboptimal splicing comes from studies with Rous sarcoma virus. In
      this report, we describe the use of chimeric introns composed of human beta
      globin and human immunodeficiency virus type 1 (HIV-1) splice sites to establish
      the basis for inefficient splicing of the intron which comprises most of the HIV
      1 env coding sequences (referred to as the tat/rev intron). S1 RNA analysis of
      transfected COS-7 cells revealed that the 3' splice site (3' ss) of this region
      was significantly less efficient than the 3' ss of the first intron of beta
      globin. Deletion of sequences flanking the tat/rev intron 3' ss demonstrated that
      the requirements for its inefficiency reside within the region that is expected
      to comprise the essential signals for splicing (i.e., the branchpoint region, the
      polypyrimidine tract, and the AG dinucleotide). Introduction of an exact copy of
      the efficient beta-globin branchpoint sequence within a highly conserved region
      rendered the tat/rev intron 3' ss highly efficient. Improvement of the
      polypyrimidine tract also increased the splicing efficiency, but to a degree
      slightly less than that obtained with the branchpoint mutation. Subsequent
      examination of the tat/rev intron 5' splice site in a heterologous context
      revealed that it is efficiently utilized. These results indicate that both a poor
      branchpoint region and a poor polypyrimidine tract are responsible for the low
      splicing efficiency of the HIV-1 tat/rev intron. It is of fundamental interest to
      establish the basis for inefficient splicing of the HIV-1 tat/rev intron since it
      may provide the key to understanding why nuclear export of mRNAs encoding HIV-1
      structural proteins is Rev dependent.

PMID- 7512160
TI  - A domain of murine retrovirus surface protein gp70 mediates cell fusion, as shown
      in a novel SC-1 cell fusion system.
AB  - Virus-induced cell fusion of the fusion-from-without type was observed in SC-1
      cells infected with Moloney murine leukemia virus when grown in NIH 3T3 cells.
      Replication-competent virus mutants with altered surface protein gp70 were
      examined. Fusion mutations were found in the proline-rich region of gp70. They
      acted on a step after binding and before or during endocytosis. The fusion
      mutants had an altered gp70 isomer pattern, presumably caused by different
      glycosylation. Other mutants with deleted glycans were analyzed, and some which
      also showed defective fusion were found. The interrelationship of the proline
      rich region, glycosylation, and fusion is discussed.

PMID- 7512161
TI  - Uncoupled expression of Moloney murine leukemia virus envelope polypeptides SU
      and TM: a functional analysis of the role of TM domains in viral entry.
AB  - Moloney murine leukemia virus ecotropic envelope expression plasmids were used to
      demonstrate that the synthesis of the retroviral envelope SU and TM polypeptides
      can be uncoupled with retention of biologic activity. By substituting a glycosyl
      phosphatidylinositol (GPI) membrane anchor for part or all of the retroviral
      envelope transmembrane protein and creating several deletion variants of the TM
      subunit, we have begun to dissect the role of the TM protein in envelope
      function. We show that a GPI-anchored envelope can be incorporated into virions
      and binds receptor. We found that the envelope cytoplasmic tail, while not
      required, influences the efficiency of retroviral transduction at some step after
      membrane fusion (possibly by interacting with core). The membrane-spanning domain
      of TM is involved in membrane fusion, and this function is distinct from its role
      as a membrane anchor. As few as eight amino acids of the putative membrane
      spanning domain are sufficient to achieve membrane anchoring of envelope but not
      to mediate membrane fusion. In addition, though not required, the membrane
      spanning domain may have some direct role in the incorporation of envelope into
      virions. Finally, the extracellular domain of TM, besides containing the putative
      fusion domain and interacting with SU, may influence the synthesis or stability
      and the glycosylation of envelope, possibly by affecting oligomerization of the
      complex and proper intracellular transit.

PMID- 7512162
TI  - Analysis of antibody responses to predominant linear epitopes of Theiler's murine
      encephalomyelitis virus.
AB  - Using synthetic peptides, we have defined the major linear antibody epitopes of
      Theiler's murine encephalomyelitis virus (TMEV), i.e., A1A (VP1(12-25)), A1Ba
      (VP1(146-160)), A1Cb (VP1(262-276)), A2A (VP2(2-16)), A2B (VP2(165-179)), and A3A
      (VP3(24-37)). A time course study with either pooled or individual sera indicates
      that susceptible SJL mice intracerebrally infected with TMEV strongly and
      selectively recognize the A1Cb epitope of VP1, compared with resistant BALB/c or
      C57BL/6 mice, which broadly recognize most of the epitopes on the different
      capsid proteins. However, antibodies from SJL mice subcutaneously immunized with
      TMEV recognize primarily A1Ba, A1Cb, and A2A epitopes. A similar predominant
      recognition of the A1Cb epitope was found with antibodies from the cerebrospinal
      fluid of intracerebrally virus-infected SJL mice. Interestingly, a substantial
      level of antibodies against the A1Cb epitope in virus-infected SJL mice is of the
      immunoglobulin G2a subclass, in contrast to an undetectable level of this
      immunoglobulin G subclass in virus-immunized SJL mice. The level of in vitro
      viral neutralization by antibodies did not correlate with the clinical signs.
      Antibodies to A1Cb, A2A, and A2B were able to neutralize viral plaque formation
      in vitro, while antibodies to A3A, A1A, and A1Ba were not.

PMID- 7512164
TI  - A single amino acid change determines persistence of a chimeric Theiler's virus.
AB  - The DA strain of Theiler's virus persists in the central nervous system of mice
      and causes chronic inflammation and demyelination. On the other hand, the GDVII
      strain causes an acute encephalitis and does not persist in surviving animals.
      Series of recombinants between infectious cDNA clones of the genomes of DA and
      GDVII viruses have been constructed. The analysis of the phenotypes of the
      recombinant viruses has shown that determinants of persistence and demyelination
      are present in the capsid proteins of DA virus. Chimeric viruses constructed by
      the different research groups gave consistent results, with one exception.
      Chimeras GD1B-2A/DAFL3 and GD1B-2C/DAFL3, which contain part of capsid protein
      VP2, capsid proteins VP3 and VP1, and different portions of P2 of GDVII in a DA
      background, were able to persist and cause demyelination. Chimera R4, whose
      genetic map is identical to that of GD1B-2A/DAFL3, was not. After exchanging the
      viral chimeras between laboratories and verifying each other's observations, new
      chimeras were generated in order to explain this difference. Here we report that
      the discrepancy can be attributed to a single amino acid difference in the
      sequence of the capsid protein VP2 of the two parental DA strains. DAFL3
      (University of Chicago) and the chimeras derived from it, GD1B-2A/DAFL3 and GD1B
      2C/DAFL3, contain a Lys at position 141, while TMDA (Institut Pasteur) and R4,
      the chimera derived from it, contain an Asn in that position. This amino acid is
      located at the tip of the EF loop, on the rim of the depression spanning the
      twofold axis of the capsid. These results show that a single amino acid change
      can confer the ability to persist and demyelinate to a chimeric Theiler's virus,
      and they pinpoint a region of the viral capsid that is important for this
      phenotype.

PMID- 7512166
TI  - From the Agency for Health Care Policy and Research.

PMID- 7512165
TI  - Mutagenic study of codons 74 and 215 of the human immunodeficiency virus type 1
      reverse transcriptase, which are significant in nucleoside analog resistance.
AB  - Mutation in the human immunodeficiency virus type 1 reverse transcriptase (RT) at
      codon 215 has been shown to play a significant role in resistance to zidovudine
      (AZT). Substitution of threonine with tyrosine or phenylalanine alone confers
      decreased susceptibility to the inhibitor. In this study we constructed a panel
      of 10 viruses with different amino acids at this codon, including 7 novel
      mutants, and assessed their susceptibilities to AZT. The majority of the new
      mutants were AZT sensitive, whereas the Thr-215-->Trp mutant was partially
      resistant (threefold less susceptible). A combination of the Thr-215-->Trp with
      the other AZT resistance mutations Lys-70-->Arg and Met-41-->Leu gave additive
      resistance. The Thr-215-->Phe virus was less AZT resistant than the Thr-215-->Tyr
      mutant, both on its own and when each was combined with the Met-41-->Leu mutant.
      These observations confirm the general hypothesis that increased bulk of the
      amino acid side chains at this position confers decreased AZT sensitivity. A
      leucine-to-valine substitution at codon 74 has previously been found to confer
      dideoxynucleoside resistance. We constructed mutants with five novel amino acid
      substitutions (Ala, Gly, Glu, Met, and Asp) at codon 74. Of these, only one (that
      with the Met substitution) retained enough RT activity to yield viable virus. It
      thus appears that there are severe structure-function constraints on the amino
      acid side chains at this position in the enzyme. The activities of the Leu-74-
      >Ala and Leu-74-->Met RT enzymes expressed in Escherichia coli appeared to have
      reduced susceptibility to ddGTP compared with the wild-type enzyme. The mutants
      described in this work may prove useful for correlation with structural studies
      of the human immunodeficiency virus type 1 RT.

PMID- 7512167
TI  - [Genetic engineering in clinical pathology].
AB  - CD36 is a glycoprotein that is expressed on platelets, monocytes, and endothelial
      cells. To analyze the mechanism of CD36 deficiency on the platelet membrane, we
      have examined the expression of mRNA by RT-PCR and the Sau96I site on PCR
      products. In cases 3, 5, and 6, we have detected the normal size, but few
      products by agarose gel electrophoresis and in all cases, several restriction
      enzyme patterns with Sau96I digestion have been observed. These findings suggest
      that transcriptional control may affect the expression of the CD36 molecule on
      the platelet membrane and a different mechanism may be present for the
      transcription of the CD36 mRNA in megakaryocytes from monocytes.

PMID- 7512163
TI  - An epitope in hepatitis C virus core region recognized by cytotoxic T cells in
      mice and humans.
AB  - Several cytotoxic T-lymphocyte (CTL) epitopes have been defined in hepatitis C
      virus (HCV) proteins. CTL may play an important role in the control of infection
      by HCV. Here, we identify a highly conserved antigenic site in the HCV core
      recognized by both murine and human CTL. Spleen cells from mice immunized with a
      recombinant vaccinia virus expressing the HCV core gene were restimulated in
      vitro with 11 peptides from the core protein. CTL from H-2d mice responded to a
      single 16-residue synthetic peptide (HCV 129-144). This conserved epitope was
      presented by a murine class I major histocompatibility molecule (H-2Dd) to
      conventional CD4- CD8+ CTL mapped by using transfectants expressing Dd, Ld, or
      Kd, but was not seen by CTL restricted by H-2b. The murine epitope was mapped to
      the decapeptide LMGYIPLVGA. The same 16-residue peptide was recognized by CTL
      from two HCV-seropositive patients but not by CTL from any seronegative donors.
      CTL from two HLA-A2-positive patients with acute and chronic hepatitides C
      recognized a 9-residue fragment (DLMGYIPLV) of the peptide presented by HLA-A2
      and containing an HLA-A2-binding motif, extending only 1 residue beyond the
      murine epitope. Therefore, this conserved peptide, seen with murine CTL and human
      CTL with a very prevalent HLA class I molecule, may be a valuable component of an
      HCV vaccine against a broad range of HCV isolates. This study demonstrates that
      the screening for CTL epitopes in mice prior to human study may be useful.

PMID- 7512169
TI  - Hepatitis C contributes to liver disease in children and adolescents with
      hemophilia.
AB  - Non-A non-B (NANB) hepatitis plays a major role in liver disease in hemophiliacs.
      HCV is known to be the predominant cause for blood-borne NANB hepatitis. A cross
      sectional study for anti-HCV and anti-HIV-1 antibodies in sera, presence of HBsAg
      in sera and liver function tests was conducted in 116 male patients with
      hemophilia (mean age: 14.6 years) in order to study the impact of hepatitis C as
      well as the significance of concurrent hepatitis B and HIV infection on the liver
      disease in hemophilic children and adolescents. 56.9% of the patients tested
      seropositive for anti-HCV; the mean age of the anti-HCV positive group was higher
      than that of the anti-HCV seronegative group (15.9 versus 11.9 years).
      Seropositivity to anti-HCV was more often associated with abnormal liver function
      than it was found in the seronegative group (37.9% versus 17%). Eight of nine
      patients positive for anti-HCV and HBsAg showed abnormal liver function tests.
      68.9% of the anti-HIV-1 positive patients were also anti-HCV positive compared to
      44.8% of the anti-HIV-1 negative patients. The liver function tests revealed an
      abnormal result in 47% of the anti-HIV-1 positive patients compared to 20.7% in
      the anti-HIV-1 negative group. In conclusion, a high seroprevalence for anti-HCV
      is detected in young patients with hemophilia which is associated with liver
      disease in a considerable number of patients when assessed by liver function
      tests. The coinfection of HCV and HBV seems to increase the risk of liver as also
      does concurrent HIV-1 infection, which is assumed to contribute to liver disease
      in a yet unexplained way.

PMID- 7512168
TI  - [A case report of coronary artery bypass grafting surgery with aprotinin in a
      patient undergoing chronic haemodialysis].
AB  - A 61-year-old patient who was receiving haemodialysis because of chronic renal
      failure developed unstable angina pectoris with three vessel disease. We
      performed successful coronary artery bypass grafting, using aprotinin to reduce
      blood loss. Blood loss during the operation was 750 ml, and during a 6 hour
      period after the operation it was 150 ml. This amount seemed to be small. No
      adverse clinical effects attributable to aprotinin were seen, and urine volume
      and plasma creatinine were not different before and after the operation. In
      summary, aprotinin is useful adjunct to open heart surgery in chronic
      haemodialysis patients.

PMID- 7512170
TI  - RCA-I lectin histochemistry after trypsinisation enables the identification of
      microglial cells in thin paraffin sections of the mouse brain.
AB  - A biotinylated lectin from Ricinus communis (RCA-I) and avidin-biotin-horseradish
      peroxidase complex (ABC) were used to identify microglial cells in 3-microns
      thick sections of formalin-fixed paraffin-embedded brains of adult mice required
      for quantitative cell kinetic studies. In 3-microns-thick sections of the mouse
      brain the staining intensity of RCA-I-positive cells compared to background
      staining was too low for evaluation, quite in contrast to rat brain. However,
      perikarya and cytoplasmic processes of microglial cells were clearly stained in
      10- and 20-microns-thick sections. The low contrast characteristic of thin mouse
      brain sections could be enhanced by pre-incubating the sections with trypsin
      before application of the lectin. We assume that different densities of RCA-I
      binding sites among microglial cells of rats and mice, respectively, are
      responsible for the different staining intensities observed. Our protocol of
      lectin staining did not influence subsequent autoradiography for studies of cell
      proliferation after [3H]thymidine application.

PMID- 7512171
TI  - Fluctuation analysis of patch-clamp or whole-cell recordings containing many
      single channels.
AB  - A novel analytical method for characterizing single-channel currents from
      recordings containing many identical, independent channels is described. The
      method is based on the assumption that the opening and closing of each single
      channel contributing to the summed current can be represented as a first-order,
      discrete-time, binary Markov chain and that the variance of the quiescent channel
      noise is known. Utilizing the first 3 moments of the record, and its power
      spectrum, all relevant single-channel parameters can be estimated. This includes
      the number of channels, the open current amplitude of a single channel, the mean
      open and closed durations and the probability of a channel being in the open
      state. In addition, the magnitude of the shot noise resulting from the flux of
      ions across the membrane can be estimated. Using fictitious multi-channel
      recordings generated by summing 2-990 independent binary Markov chains together
      with additive white noise, we have tested the reliability of the method in
      estimating the statistics of single channels. Finally, we discuss how the
      technique may be extended to cope with data which has been low-pass filtered, and
      also suggest further experiments which the technique now makes possible.

PMID- 7512172
TI  - Indomethacin potentiates the induction of HL60 differentiation to neutrophils, by
      retinoic acid and granulocyte colony-stimulating factor, and to monocytes, by
      vitamin D3.
AB  - We have confirmed previous observations that HL60 cells treated with a
      combination of 10 nM retinoic acid (RA), and 30 ng/ml granulocyte colony
      stimulating factor (G-CSF) differentiate efficiently towards neutrophils, as
      characterized by their growth arrest and acquisition of phagocytic ability. Such
      low concentrations of RA alone provoked only a small proportion of HL60 cells to
      differentiate, and G-CSF alone provoked no differentiation. In the presence of 30
      microM indomethacin (an inhibitor of the enzyme cyclooxygenase that catalyses the
      first step of prostanoid synthesis), the onset of differentiation provoked by RA
      plus G-CSF was more rapid, but the final proportion of mature cells was
      unchanged. Indomethacin also potentiated the growth arrest and differentiation of
      cells in response to 10 nM RA alone. Although the potentiating effect of
      indomethacin on RA-induced differentiation occurred at several indomethacin and
      RA concentrations, it was only apparent when the RA concentration used was alone
      sufficient to induce a small proportion of cells to differentiate. Indomethacin
      shifted the G-CSF dose-response curve of cells treated with 10 nM RA to lower G
      CSF concentrations. 1 alpha,25-dihydroxy vitamin D3 (VitD3) induces HL60 cells to
      differentiate to monocytes and indomethacin also potentiated the differentiation
      of HL60 cells in response to low doses of VitD3 5,8,11-eicosatriynoic acid, an
      inhibitor of 5-lipoxygenase and 12-lipoxygenase, neither potentiated neutrophil
      differentiation of HL60 cells, nor prevented indomethacin potentiation of the
      differentiation of RA-primed cells. Treatment of cells with dexamethasone, a
      steroid whose effects include inhibition of arachidonate mobilization by
      phospholipase A2, potentiated RA-primed neutrophil differentiation in a manner
      similar to indomethacin. These observations suggest that an arachidonate
      metabolite formed downstream of cyclooxygenase suppresses differentiation of HL60
      cells both to neutrophils and monocytes, probably by inhibiting some event
      essential to commitment to differentiation.

PMID- 7512173
TI  - Transforming growth factor alpha expression in normal human blood eosinophils:
      differential regulation by granulocyte-macrophage colony-stimulating factor and
      interleukin-3.
AB  - We have previously demonstrated a constitutive expression of transforming growth
      factor alpha (TGF-alpha) in normal human blood eosinophils, both at the mRNA and
      protein level. This may indicate a novel function of the eosinophil, the
      regulation of which has not been clarified. Therefore human white blood cells
      (WBC) were treated with potential regulators of eosinophil function. Northern
      blot analysis demonstrated that human recombinant granulocyte-macrophage colony
      stimulating factor (GM-CSF) or interleukin-3 (IL-3) caused a time and dose
      dependent 2- to 3-fold increase of TGF-alpha mRNA levels, in relation to
      incubation in the absence of cytokine; maximal response was attained within 4 h
      of incubation. In contrast, IL-5 failed to influence the expression of the TGF
      alpha gene. In situ analysis of GM-CSF- or IL-3-stimulated cells showed that
      eosinophils remained the sole cell type expressing TGF-alpha mRNA. However,
      whereas GM-CSF significantly induced, within 1 h, release of immunoreactive TGF
      alpha protein, IL-3 was insufficient in this respect. In conclusion, our findings
      indicate that expression of TGF-alpha gene and protein in normal blood
      eosinophils is differently regulated by GM-CSF and IL-3.

PMID- 7512174
TI  - Expression of the c-kit proto-oncogene in myeloproliferative disorders and
      myelodysplastic syndromes.
AB  - The c-kit proto-oncogene is the receptor gene for the stem cell growth factor.
      Little is known about the distribution and role of this gene product in malignant
      hematopoiesis. We analysed here the expression of c-kit in myeloproliferative
      disorders (MPDs), including chronic myelogenous leukemia (CML), essential
      thrombocythemia (ET), polycythemia vera (PV), and idiopathic myelofibrosis (IMF)
      and in the myelodysplastic syndromes (MDS). The c-kit expression of peripheral
      blood mononuclear cells was measured both at the messenger RNA level using
      Northern analysis, the RNA dot blot technique with densitometric quantification,
      the sensitive reverse transcription polymerase chain reaction, and at the protein
      level using immunofluorescence with monoclonal antibodies. There was a
      statistically significant increase in c-kit messenger levels in CML, ET, PV, IMF,
      and MDS as compared with controls (healthy volunteers). The percentage of c-kit
      protein expressing cells was also higher than in the controls in these disorders.
      There was a significant correlation of the c-kit protein expression with the CD34
      antigen of the cells. Expression correlated with the phase of the disease, being
      highest in the blast crisis of CML and in the RAEB/RAEBt phases of MDS. The data
      suggest that increased amounts of circulating stem/progenitor cells with c-kit
      receptor are found in MPDs and MDS. It is possible that elevated c-kit expression
      could maintain the affected clone in MPDs and MDS.

PMID- 7512176
TI  - Epitope tagging of DAB389IL-2: new insights into C-domain delivery to the cytosol
      of target cells.
AB  - The fusion toxin DAB389IL-2 is composed of the catalytic (C) and transmembrane
      (T) domains of native diphtheria toxin to which human interleukin-2 (IL-2) has
      been genetically fused (1,2). Following binding to the IL-2 receptor, the fusion
      toxin is internalized by receptor mediated endocytosis, and upon acidification of
      the endocytic vesicle, the T domain spontaneously inserts into the membrane, and
      facilitates the delivery of the C domain to the cytosol (3,4). In order to
      further study the process by which the C domain is delivered to the target cell
      cytosol, we genetically fused an eleven amino acid epitope derived from the
      vesicular stomatitis virus (VSV) G protein to the N-terminal end of DAB389IL-2.
      The epitope labelled fusion toxin, VSV-G-DAB389IL-2, was found to retain IL-2
      receptor specific binding and cytotoxic activity. Target cells were incubated for
      various times in the presence of VSV-G-DAB389, fixed and then treated with anti
      VSV G and FITC conjugated secondary antibody. Laser scanning confocal microscopy
      was used to determine the location of the fluorescent signal. The VSV-G epitope
      tagged fusion toxin was found only to be associated with small vesicles that were
      situated adjacent to the plasma membrane. These results suggest that the C domain
      of the fusion toxin is associated with an early intracellular compartment and is
      rapidly delivered to the cytosol. Since channel formation by the T domain is
      necessary for the delivery of the C domain, it follows that T domain insertion
      into the membrane also occurs early in the intoxication pathway.

PMID- 7512175
TI  - Mutations in the ras proto-oncogenes in patients with myelodysplastic syndromes.
AB  - Activation of the N- and K-ras proto-oncogenes is the most common molecular
      abnormality in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
      In retrospective studies, approximately 3-36% of MDS patients were reported to
      harbor a mutated ras proto-oncogene, with some series suggesting the presence of
      ras-mutations are associated with progressive disease and a poor prognosis. Since
      hematopoietic growth factors such as granulocyte colony-stimulating factor (G
      CSF) are currently used for therapy in MDS but may stimulate the proliferation of
      leukemic cells, we assessed the frequency and significance of ras mutations in 27
      MDS patients, 15 of whom underwent G-CSF therapy. Patients were analyzed for the
      presence of mutations in codons 12, 13, and 61 of the N- and K-ras proto
      oncogenes. Only three patients (11%, two refractory anemia with excess of blasts
      (RAEB), one RAEB in transformation (RAEB-T)) harbored activated ras oncogenes
      with the mutations localized in N-ras codons 12 and 61. Patients were followed
      for periods of up to 4 years or until death supervened. Patients exhibiting ras
      mutations were no more likely to develop AML compared to ras-negative patients
      (1/3 vs. 10/24) or to have decreased survival (p = 0.64). These data indicate
      that, in this group of MDS patients, ras mutations do not appear to correlate
      with a poor prognosis, and do not adversely interact with exogenously
      administered G-CSF.

PMID- 7512177
TI  - Reverse transcriptase is an important factor for the primer tRNA selection in HIV
      1.
AB  - During assembly, HIV-1 selectively packages tRNA(Lys3), the primer tRNA for
      reverse transcriptase (RT). Because of tRNA(Lys3)'s ability to interact with RT,
      RT may be the viral protein which binds to primer tRNA and carries it into the
      virus. We have tested this hypothesis by measuring the amount of tRNA(Lys3)
      incorporated into wild type and RT(-) virus, and have also measured the tRNA
      tightly associated with the RNA genome, a characteristic of primer tRNA. We find
      that in RT(-) HIV-1, primer tRNA(Lys3) is reduced approximately 10 fold compared
      to wild type virus (which contains 8 molecules tRNA(Lys3)/virus), and the tRNA
      found tightly associated with the RNA genome is also greatly reduced in these
      mutant virus.

PMID- 7512179
TI  - Mature reverse transcriptase (p66/p51) is responsible for low levels of viral DNA
      found in human immunodeficiency virus type 1 (HIV-1).
AB  - Reverse transcription of the HIV RNA genome is thought to occur in the host cell
      cytoplasm after viral adsorption. However, viral DNA has been isolated in cell
      free virus particles. We have quantitated by polymerase chain reaction (PCR)
      amplification the amount of viral DNA in virions as compared to RNA. Virus
      produced by proviral DNA transfections of cos-7 cells or by chronically-infected
      H9 cells; neither of which express the cell surface CD4 receptor, contained at
      least 1000 times more viral RNA than DNA. In contrast, only 60 times more RNA
      than DNA was present in virus particles produced by transfection of Jurkat cells,
      which were CD4-positive and thus potentially susceptible to superinfection.
      Protease-defective virus, carrying only the precursor of reverse transcriptase
      (RT) p160gag-pol, contained virtually no detectable DNA. These results indicate
      that only mature RT (p66/p51) and not its precursor (p160gag-pol) is responsible
      for the presence of viral DNA in HIV.

PMID- 7512178
TI  - Identification of novel mutations that confer drug resistance in the human
      immunodeficiency virus polymerase gene.
AB  - We generated variants of the human immunodeficiency virus type 1 (HIV-1) that are
      resistant to 2',3'-dideoxycytidine (ddC) and 2',3'-didehydro-3'-deoxythymidine
      (d4T) by in vitro selection in MT-4 cells. Portions of flanking protease and
      integrase sequences as well as the complete reverse transcriptase (RT) open
      reading frame of these viruses were cloned and sequenced, using polymerase chain
      reaction (PCR)-based methods. Mutations were observed at amino acid position 65
      (Lys-->Arg; AAA-->AGA) when ddC was employed in the selection procedure and at
      site 50 (Ile-->Thr; ATT-->ACT) when d4T was used. We confirmed the ability of
      these mutations to confer diminished sensitivity for these compounds by site
      directed mutagenesis, in which these mutations were inserted into the pol gene of
      infectious recombinant HXB2-D DNA. Viruses that contained the site 65 mutation
      possessed approximately 5-10 fold resistance against ddC when compared with wild
      type HXB2-D. The site 50 mutation conferred approximately 30-fold resistance to
      d4T in these same assays. Similar results were obtained using primary cord blood
      lymphocytes in drug resistance assays, indicating that these mutations could
      confer drug resistance in more than one cell type and that the respective
      mutations could be expressed in cells of primary origin. No cross-resistance
      against 3'-azido-3'-deoxythymidine (AZT) was noted for either the site 65 or 50
      mutations.

PMID- 7512180
TI  - Activating mutations of the c-kit proto-oncogene in a human mast cell leukemia
      cell line.
AB  - The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play
      a crucial role in mast cell growth and differentiation. In a human mast cell
      leukemia cell line (HMC-1), KitR was found to be constitutively phosphorylated on
      tyrosine, activated and associated with phosphatidylinositol 3-kinase (P13K) in
      the absence of autocrine production of SCF. Sequencing of c-kit cDNA revealed
      that c-kit genes of HMC-1 cells were composed of a normal, wild-type allele and a
      mutant allele with two point mutations in codon 560 and codon 816, resulting in
      intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp,
      respectively. Murine c-kit mutants encoding Gly-559 and/or Val-814, corresponding
      to human Gly-560 and/or Val-816, were constructed by site-directed mutagenesis
      and expressed in cells of a human embryonic kidney cell line (293T). In the
      transfected cells, KitR (Gly-559 + Val-814) and KitR (Val-814) were strikingly
      phosphorylated on tyrosine and activated in the absence of SCF, whereas tyrosine
      phosphorylation and activation of KitR (Gly-559) or wild-type KitR was modest or
      little, respectively. These results suggest that constitutive activation of KitR
      in HMC-1 results from the activating mutations of c-kit gene, and raise the
      possibility that the activating mutations, particularly at codon 814 of murine c
      kit or at codon 816 of human c-kit, may participate in oncogenesis of mast cells.

PMID- 7512181
TI  - The bovine leukemia virus (BLV) envelope glycoprotein gp51 as a general model for
      the design of a subunit vaccine against retroviral infection: mapping of
      functional sites through immunological and structural data.
AB  - Further advances in retroviral vaccine development require a better understanding
      of the antigenic structure of the envelope complex which is directly involved in
      infectivity events such as receptor recognition and membrane fusion. To design an
      optimal vaccine against BLV infection, we chose an approach based on the use of
      synthetic peptides covering 78% of the gp51 sequence in order to select only
      those segments that could induce a protective response via cellular and humoral
      immunity. On the other hand, we built a model of the BLV env glycoprotein 3D
      organization, based upon the very sensitive hydrophobic cluster analysis (HCA).
      The major information highlighted from this model is that the two loops, against
      which the most efficient neutralizing antipeptides antibodies are directed
      against, are in close proximity at the top of the "head" and could represent a
      potential site for receptor binding. These two peptides are of particular
      interest since they induce also a helper T-cell response. We further propose that
      the BLV envelope glycoprotein oligomerizes as a trimer.

PMID- 7512183
TI  - Effect of ageing on monoamine turnover in the prefrontal cortex of rats.
AB  - Turnover of dopamine (DA), serotonin (5-hydroxytryptamine) (5-HT), noradrenaline
      (NA) and their metabolites has been measured in control and aged rats. In
      addition, tyrosine hydroxylase (TH) activity has been studied. After pargyline
      treatment, the turnover rates of DA, NA, 3,4-dihydroxyphenylacetic acid (DOPAC),
      3-methoxytyramine (3-MT), 5-HT and 5-hydroxy-3-indolacetic acid (5-HIAA) and TH
      activity increased in aged rats with respect to controls. At the same time the DA
      and 3-MT turnover increase are consistent with the hypothesis that enhanced
      release of DA may participate in some degenerative processes in ageing. After
      probenecid treatment, the turnover of homovanillic acid (HVA) was lower in aged
      rats than in controls. However, DOPAC turnover was higher in the aged rats. The
      DOPAC increase seems to indicate a reinforcement of this pathway in aged rats.

PMID- 7512182
TI  - Characterization of monoclonal antibodies directed against the gp46 of human T
      cell leukemia virus type I.
AB  - Essential HTLV-I biological functions depend on the structural motives of the
      surface glycoprotein (gp46). Monoclonal antibodies (mAbs) have been generated in
      order to identify functional regions of gp46. We obtained three monoclonal
      antibodies (3F3F10, 4F5F6 and 7G5D8) by immunizing Balb/c mice with beta
      propiolactone inactivated HTLV-I producing cells and partially purified gp46. The
      mAbs are of the IgG 1 subclass. They have been characterized by western blot
      analysis, reactivity with HTLV-I and HTLV-II producing cells and ELISA binding
      assays using synthetic peptides. The immunoblot analysis performed with sheets
      prepared with the virus released by HUT 102 and 2060 cells (an HTLV-I virus
      producing cell line established in our laboratory) indicate that the three mAbs
      recognize a 46 kDa product as did the anti -gp46 mAb 0.5 alpha (18). Reactivity
      of the three mAbs with various cell lines was examined by indirect
      immunofluorescence assay. The mAb 7G5D8 stained strongly the membrane of all HTLV
      I producing cells (MT2, C91/PL, HUT102 and cells of seven lines established in
      our laboratory and by A. Gessain); uninfected lymphoid cells (HSB-2, MOLT 4, CEM
      and PHA activated lymphocytes from normal donors) were negative. Interestingly
      cells of a HTLV-II producing line (344 MO) were positive. The mAbs 3F3F10 and
      4F5F6 reacted with the same cells as did 7G5D8 but the fluorescence intensity was
      much lower than that observed with this later. A long synthetic peptide
      corresponding to the immunodominant region of the gp46 defined by the amino acids
      175-199 and 10-mer peptides overlapping this region were used in an approach to
      identify the recognized epitope(s). The long 175-199 peptide was recognized by
      the three mAbs. 3F3F10 and 4F5F6 recognized none of the 10-mer peptides whereas
      7G5D8 bound to 186-195 and 182-191 peptides. In addition 7G5D8 did not inhibit
      either syncytia formation or virus infection. In view of the data concerning the
      previously described mAbs 0.5 alpha, LAT 27 (5) and KE36-11 (6), our results
      suggest that the epitope recognized by 7G5D8 is different from those recognized
      by the former ones. As the 183-191 sequence corresponds to a region in which HTLV
      I and HTLV-II harbour six common amino acids and two similar ones, this is
      consistent with the observation that 7G5D8 stained the HTLV-II producing cells
      344 MO as well as all HTLV-I producing ones. Altogether our data support the
      hypothesis whereby this epitope recognized by 7G5D8 is contained within a
      sequence defined by amino acids 183-191.

PMID- 7512184
TI  - Characterization of an SH2 containing protein tyrosine phosphatase in rat parotid
      gland acinar cells.
AB  - Rat parotid glands were shown to possess protein phosphatase activity capable of
      catalyzing the dephosphorylation of several model phosphatase substrates,
      including p-nitrophenyl phosphate, tyrosine phosphorylated myelin basic protein
      and serine phosphorylated casein. A portion of this activity closely resembled
      dephosphorylation patterns of known protein tyrosine phosphatases. The reaction
      showed sensitivity to sodium orthovanadate, proceeded efficiently in the presence
      of metal chelators and favored acidic pH for optimum activity. Cell lysates from
      EGF- or isoproterenol-stimulated parotid glands, when immuno-precipitated with
      anti-Syp antibody, showed the induction of protein tyrosine phosphatase activity
      significantly higher than the unstimulated controls. The protein of M(r) = 65kDa
      also had elevated levels of tyrosine phosphorylation following isolation from
      cells treated to undergo proliferation. Thus parotid gland acinar cells possess
      protein tyrosine phosphatase activity of the PTPase 1D class associated with
      inducible cell growth, in addition to other phosphatases.

PMID- 7512185
TI  - 3-isobutyl-1-methylxanthine decreases renal cortical interstitial levels of
      adenosine and inosine.
AB  - The purpose of this study was to test the hypothesis that endogenous cyclic AMP,
      via metabolism by phosphodiesterase, contributes to interstitial levels of
      adenosine in the renal cortex in vivo. This hypothesis was tested by determining
      the effects of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, on
      renal cortical interstitial levels of adenosine and inosine. Changes in renal
      cortical interstitial adenosine and inosine levels were assessed in rats by
      implanting microdialysis probes into the renal cortex and measuring adenosine and
      inosine levels in the dialysate exiting the kidney using high performance liquid
      chromatography. When added to the dialysate entering the kidney at concentrations
      of 0.5, 1 and 2.5 mM, 3-isobutyl-1-methylxanthine significantly and dose
      dependently decreased interstitial levels of both adenosine and inosine. The
      percentage changes from baseline of interstitial levels of adenosine and inosine
      were: -39 +/- 6% and -19 +/- 6%, respectively, with 0.5 mM 3-isobutyl-1
      methylxanthine; -45 +/- 7% and -24 +/- 8%, respectively, with 1 mM 3-isobutyl-1
      methylxanthine; and -56 +/- 12% and -38 +/- 8%, respectively, with 2.5 mM 3
      isobutyl-1-methylxanthine. These data suggest that in the renal cortex, cyclic
      AMP metabolism via phosphodiesterase is an important source of renal interstitial
      adenosine.

PMID- 7512186
TI  - A plasmid-encoded rfbO:54 gene cluster is required for biosynthesis of the O:54
      antigen in Salmonella enterica serovar Borreze.
AB  - Previous studies demonstrated that the presence of a 7-8 kb plasmid is correlated
      with expression of the lipopolysaccharide (LPS) O:54 antigen in several
      Salmonella enterica serovars. In this study, a 6.7 kb plasmid from a field
      isolate of S. enterica serovar Borreze was shown to encode enzymes responsible
      for the synthesis of the O:54 polysaccharide. Curing the plasmid results in
      simultaneous loss of smooth O-polysaccharide-substituted LPS molecules and O:54
      serotype. SDS-PAGE analysis of other O:54 isolates indicated that the O:54 O
      polysaccharide can be co-expressed with an additional O-polysaccharide, likely
      encoded by chromosomal genes. The structure of the O:54 polysaccharide was
      determined by a combination of chemical and nuclear magnetic resonance (NMR)
      methods and was found to be an unusual homopolymer of N-acetylmannosamine (D
      ManNAc) residues. The polysaccharide contained a disaccharide repeating unit with
      the structure:-->4)-beta-D-ManpNAc-(1-->3)-beta-D-ManpNAc-(1--> This structure
      does not resemble other O-polysaccharides in S. enterica. To examine the role
      played by plasmid functions in synthesis of the O:54 polysaccharide, the 6.7 kb
      plasmid was cloned to produce a hybrid plasmid (pWQ800) in pGEM-7Zf(+). In
      Escherichia coli K-12 delta rfb, pWQ800 directed the synthesis of authentic O:54
      polysaccharide. Polymerized O:54 polysaccharide was also produced in S. enterica
      serovar Typhimurium rfb and rfc mutants. From these data, we conclude that pWQ800
      carries the rfbO:54 gene cluster and synthesis of the O:54 polysaccharides does
      not require host chromosomal rfb functions. However, synthesis of the O:54
      polysaccharide requires the function of the rfe and rffE genes which are part of
      the gene cluster encoding enzymes involved in biosynthesis of enterobacterial
      common antigen. The rffE gene product synthesizes the O:54 precursor, uridine
      diphospho-N-acetylmannosamine. This is the first description of a plasmid-encoded
      rfb gene cluster in Salmonella.

PMID- 7512187
TI  - Evidence for a regulatory function of the histone-like Escherichia coli protein H
      NS in ribosomal RNA synthesis.
AB  - We have isolated a small Escherichia coli protein which stably interacts with
      ribosomal RNA P1 promoter DNA. We present evidence showing that the protein is
      identical to the histone-like E. coli protein, H-NS (H1). Binding of H-NS to the
      P1 promoter region is dependent on the DNA curvature. Mapping the H-NS-DNA
      contact sites by nuclease protection and high-resolution footprinting techniques
      reveal three H-NS-binding domains, and contacts of the protein in the major
      groove of the bent DNA. The binding region extends from position -18 to -89,
      relative to the P1 transcription start site, and shows an overlap with the known
      binding sites for Fis, another E. coli protein, which acts as transcriptional
      activator of P1. The binding of H-NS does not displace Fis; instead, heterologous
      complexes are formed. Apparently, H-NS and Fis bind to separated curved DNA
      segments, with the planes of the curves pointing into different directions. In
      vitro transcriptional analyses demonstrate that H-NS represses rRNA P1 promoter
      directed transcription. Repression is most pronounced in the presence of Fis.
      Thus, H-NS seems specifically to antagonize Fis-dependent activation. No
      comparable inactivation is observed for the second rRNA promoter P2.

PMID- 7512188
TI  - A harder thing than triumph: roles of fathers of children with disabilities.
AB  - Researchers have recently begun to address the role of fathers of children with
      disabilities, which often casts the father as peripheral to the child's
      development. However, my review of the relevant literature indicates that these
      fathers express more interest in the needs of their children than customarily
      thought. Many fathers apparently want more involvement than they currently have
      but are constrained by "gate-keeping" roles of mothers and the structure of their
      children's programs. Further, research and popular literature show that although
      fathers have recognized roles to play, it is difficult for them to receive credit
      for their efforts, which may be due to the lack of routines to foster father/male
      involvement in programs for children with disabilities.

PMID- 7512189
TI  - The 16S rRNA sequence and genome sizing of tributyltin resistant marine
      bacterium, strain M-1.
AB  - The 16S rRNA of the tributyltin resistant marine bacterium, strain M-1, was
      partly sequenced to confirm the taxonomic status. The results indicated that this
      bacterium should be classified under the genus Alteromonas, instead of a previous
      report in which this strain was identified as a Vibrio. The genome size of this
      strain was also measured by pulsed field gel electrophoresis (PFGE) using a
      contoureclamped homogeneous electric field. The strain was found to contain a
      genome size of 2,240 kilo base pairs, whereas Alteromonas nigrifaciens and
      Shewanella putrefaciens had 2,040 and 2,383 kilo base pairs, respectively. This
      is the first report of the genome sizing of the genus Alteromonas by PFGE.

PMID- 7512192
TI  - The role of inhaled steroids in the treatment of bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia has been well described in premature infants requiring
      mechanical ventilation. Systemic steroids are one of many treatment modalities
      used in the management of these infants, but these agents have been associated
      with a number of adverse effects. Aerosolized therapy has been proposed as an
      alternative in order to minimize the systemic complications that occur with the
      parenteral route. The initial reports of inhaled steroids, although limited, have
      shown promising results with minimal side effects. This article addresses the
      mechanism of action, the role in therapy, and potential complications associated
      with the use of inhaled steroids in the treatment of bronchopulmonary dysplasia.

PMID- 7512190
TI  - Radiation therapy for alveolar soft-part sarcoma.
AB  - A clinical experience with radiotherapy in 18 patients with alveolar soft-part
      sarcoma is presented. Adjuvant radiotherapy was associated with prolonged local
      control in six of six patients without metastatic disease at diagnosis; later one
      patient relapsed systematically. Meaningful palliation was achieved in all
      patients with extra-skeletal (and possibly skeletal) metastatic disease.
      Radiation therapy may be beneficial for patients with alveolar soft-part sarcoma
      by enhancing local control achieved with limited surgery, by retarding
      progression of metastatic deposits, and by providing meaningful palliation.

PMID- 7512191
TI  - Pediatric Hodgkin's disease in Costa Rica: twelve years' experience of primary
      treatment by chemotherapy alone, without staging laparotomy.
AB  - This is a prospective and nonrandomized study in which 86 children with
      previously untreated Hodgkin's disease (HD) were clinically staged (CS) and
      treated with chemotherapy (CT) alone. Fifty-two (CS IA-38, IIA-7, IIB-3, IIIA-4)
      received six courses of cyclophosphamide, vinblastine, procarbazine, and
      prednisone (CVPP). Ten (CS IA with peripheral nodes) received only three courses
      of CVPP with a reinforcement of C on day 8. Twenty-four (CS IIIB-18, IVA-2, IVB
      4) received six courses of CVPP alternating with six courses of epirubicin,
      bleomycin, and vincristine (EBO). Surgical staging was not performed in any
      patient. Two patients (CS IIIB) had partial remission and died from progressive
      disease. Seventy out of 86 children have not relapsed and are in complete
      remission with a median follow-up of 65 months (range 13-156 months); 14 children
      relapsed seven to 37 months from diagnosis (median 16 months); one of them (IV B)
      died of disease. Thirteen are in second and third remission (median 55 months).
      Actuarial five year survival rates and relapse-free survival rates are 100% and
      90% for CS I to IIIA and 81% and 60% for CS IIIB and IV, respectively. As a
      result of this study, we can conclude that in developing countries most of the
      children with HD staged by noninvasive diagnostic techniques can be cured with CT
      alone as primary treatment and thus will not suffer from the late effects of
      radiotherapy (RT) and the morbidity of laparotomy and splenectomy. RT alone or
      with other CT combinations should be considered for children who develop relapse
      of HD.

PMID- 7512193
TI  - Tad1-1, an active LINE-like element of Neurospora crassa.
AB  - Tad is a LINE-like retrotransposon of Neurospora crassa. The element was
      originally detected and cloned using the am gene as a transposon trap in hybrid
      strains derived from a cross of Adiopodoume (a wild collected strain) and a
      laboratory strain devoid of Tad elements. We report the cloning and sequencing of
      an active Tad element, Tad1-1, which is capable of independent transposition.
      Transposition was demonstrated by screening for transfer of the element from a
      donor nucleus that contained the Tad1-1 element as the only active Tad, into a
      naive nucleus within a forced heterokaryon. We also report here the sequence
      analysis of Tad1-1, and its comparison with the sequence of another active
      element, Tad3-2. These elements are approximately 7 kb in length. They contain
      two long open reading frames (ORFs) encoded on the strand of the same polarity as
      the full-length transcript. ORF1 encodes a putative protein of 486 amino acids.
      Homology to the first ORF of other LINE elements is confined to three cysteine
      rich motifs, located near the carboxy-terminus, that are thought to be involved
      in binding nucleic acids. The second ORF is 1156 amino acids in length and shows
      homology to the reverse transcriptase domains of various retroviruses and
      retrotransposons. Tad1-1 and Tad3-2 differ in only ten positions over their whole
      length.

PMID- 7512194
TI  - Essential role of tyrosine residues 1131, 1135, and 1136 of the insulin-like
      growth factor-I (IGF-I) receptor in IGF-I action.
AB  - The insulin and insulin-like growth factor-I (IGF-I) receptors are related
      heterotetramers consisting of two extracellular ligand-binding alpha-subunits and
      two transmembrane beta-subunits whose cytoplasmic domains exhibit tyrosine kinase
      activity. Previous studies have shown that ATP binding by the cytoplasmic
      tyrosine kinase domains of these receptors is necessary to initiate the signal
      transduction pathway triggered by ligands or by ligand-mimetic antibodies,
      suggesting that receptor autophosphorylation is a necessary proximal step in this
      pathway. In the case of the insulin receptor, it has additionally been
      demonstrated that a cluster of three tyrosines in the kinase domain itself are
      the first to be phosphorylated, and that autophosphorylation of these particular
      residues is necessary for receptor activity. Using stably transfected NIH-3T3
      cell lines, we now show that mutation of the analogous residues in the IGF-I
      receptor abolishes all short, intermediate, and long-term responses to IGF-I.
      These data suggest that the initial mechanisms of activation of the insulin and
      IGF-I receptors are very similar. Additionally, we have identified two
      parameters, induction of c-fos gene expression and ornithine decarboxylase enzyme
      activity, which are extremely sensitive to IGF-I stimulation and which will be
      particularly useful in evaluating the biological activity of other mutated
      versions of the IGF-I receptor.

PMID- 7512195
TI  - Activation of protein kinase C alpha inhibits insulin-stimulated tyrosine
      phosphorylation of insulin receptor substrate-1.
AB  - Chinese hamster ovary (CHO) cells were transfected with a cDNA encoding protein
      kinase C alpha (PKC) and a cell line (CHO-PKC alpha) expressing approximately 7
      fold greater amounts of PKC as the parental cells were isolated. Activation of
      PKC by 12-O-tetradecanoylphorbol-13-acetate in the CHO-PKC alpha cells inhibited
      by approximately 75% the: 1) insulin-stimulated increase in antiphosphotyrosine
      precipitable phosphatidylinositol 3-kinase activity in these cells; 2) insulin
      stimulated increase in PI 3-kinase activity associated with insulin receptor
      substrate-1; and 3) tyrosine phosphorylation of the endogenous substrate, insulin
      receptor substrate-1. In contrast, 12-O-tetradecanoylphorbol-13-acetate treatment
      did not inhibit any of these responses in the parental CHO cells. These results
      indicate that excessive PKC activity can interfere in a very early step in
      insulin receptor signaling and are consistent with the hypothesis that excessive
      PKC activity may contribute to some states of insulin resistance.

PMID- 7512196
TI  - Insulin-like growth factor-binding protein-2: the effect of human chorionic
      gonadotropin on its gene regulation and protein secretion and its biological
      effects in rat Leydig cells.
AB  - Human CG (hCG) and insulin-like growth factor-I (IGF-I) have synergistic effects
      on Leydig cell function. Leydig cells express high affinity IGF-I receptors. The
      number of IGF-I receptors and IGF-I receptor mRNA levels can be up-regulated by
      hCG. The most abundant mRNA species of the IGF binding proteins (IGFBPs) in rat
      Leydig cells is IGFBP-2. In the present study, we investigated the effect of hCG
      on IGFBP-2 transcription, mRNA accumulation, and protein production/secretion.
      Biological effects of IGFBP-2 on Leydig cells were also examined. Rat Leydig
      cells were purified from testes using centrifugal elutriation followed by Percoll
      gradient centrifugation. Cells were cultured for 24 h and then treated with or
      without hCG (10 ng/ml) for 6 h. The expression of IGFBP-2 mRNA was decreased by
      hCG in a dose-dependent manner, and at a concentration of 10 ng/ml the expression
      of IGFBP-2 mRNA was reduced by 50%. As early as 2 h after the addition of hCG,
      there was a significant decrease in IGFBP-2 mRNA accumulation. To evaluate the
      mechanism(s) responsible for decreased IGFBP-2 gene expression by hCG, the effect
      of hCG on the rate of transcription and stability of the mRNA was determined.
      Human CG (10 ng/ml) reduced the IGFBP-2 transcription rate by 32%/h in comparison
      with the control, while the half-life (t1/2) of mRNA remained unaltered (hCG
      treated cells, 0.58 h; control cells, 0.51 h). IGFBP-2 with a molecular size of
      33 kilodaltons was detected as a major band in the Western ligand blot.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7512199
TI  - Benzyl acetate: from mutagenic carcinogen to non-mutagenic non-carcinogenic in 7
      years?

PMID- 7512197
TI  - Acrolein genotoxicity in Drosophila melanogaster. II. Influence of mus201 and
      mus308 mutations.
AB  - The influence of mus201 and mus308 mutants on acrolein mutagenicity was analyzed
      with the Drosophila melanogaster sex-linked recessive lethal test (SLRL), using
      the maternal approach, to further study the mechanisms of action of this
      chemical. The hypermutability indices obtained were 2.59 for mus201 and 0.52 for
      mus308 conditions. Statistical analysis indicates that whereas part of the
      acrolein-induced lesions are repaired by excision mechanism, as expected for a
      cyclic agent, there is no demonstrable influence of the mus308 locus on the
      mutagenicity of this chemical.

PMID- 7512198
TI  - Transgenic systems for in vivo mutational analysis (Provost et al., Mutation
      Res., 288 (1993) 133-149)

PMID- 7512200
TI  - The role of programmed cell death in the toxicity of the mutagens, ethyl
      methanesulfonate and N-ethyl-N'-nitrosourea, in AHH-1 human lymphoblastoid cells.
AB  - In order to determine the pathway for cell death in alkylating agent-exposed
      human lymphoblastoid cells, AHH-1 cells were exposed to either ethyl
      methanesulfonate (EMS) or ethyl nitrosourea (ENU) and the effect on relative cell
      growth and plating efficiency quantified. Flow cytometric (FCM) assays were
      utilized to quantify cell viability and to determine if cell death occurred
      through necrosis or apoptosis. As expected, exposure to the simple ethylating
      agents resulted in concentration-dependent decreases in plating efficiencies at
      each time interval after exposure (Days 0, 2, 3 and 7). EMS exposure did not
      significantly affect the relative cell growth, in contrast to ENU exposure, which
      inhibited cell growth. The FCM viability assay, based on light scatter
      characteristics, revealed that exposure to either alkylating agent resulted in a
      significant reduction in the percentage of viable cells. The results of the FCM
      dye-exclusion assays revealed that while necrosis occurred in EMS- and ENU
      exposed cells, the primary manner of cell death was apoptosis. AHH-1 cells were
      stained with propidium iodide and fluorescein diacetate, the population of cells
      sorted electronically and the cell type (necrotic, apoptotic or viable) confirmed
      morphologically. Our results clearly indicate that exposure to EMS or ENU results
      in the movement of AHH-1 cells into the pathway for apoptosis and cell death.

PMID- 7512201
TI  - tert.-butyl hydroperoxide-mediated DNA base damage in cultured mammalian cells.
AB  - tert.-Butyl hydroperoxide has been utilized to study the effect of oxidative
      stress on living cells; however, its effect on DNA bases in cells has not been
      characterized. In the present work, we have investigated DNA base damage in
      mammalian cells exposed to this organic hydroperoxide. SP2/0 derived murine
      hybridoma cells were treated with 4 concentrations of tert.-butyl hydroperoxide
      for varying periods of time. Chromatin was isolated from treated and control
      cells and subsequently analyzed by gas chromatography-mass spectrometry with
      selected-ion monitoring for DNA base damage. Quantification of damaged DNA bases
      was achieved by isotope-dilution mass spectrometry. The amounts of 8 products
      were significantly higher than control levels in cells treated with tert.-butyl
      hydroperoxide at a concentration range of 0.01-0.1 mM. At concentrations from 1.0
      to 10 mM, product formation was inhibited and the amounts of products were
      similar to those in control cells. The bimodal nature of the dose-response may be
      qualitatively analogous to previous reports of bimodal killing of E. coli
      bacteria by hydrogen peroxide. The nature of the identified DNA base lesions
      suggests the involvement of the hydroxyl radical in their formation. tert.-Butyl
      hydroperoxide is known to produce the tert.-butoxyl radical in reactions with
      metal ions. However, it is unlikely that the tert.-butoxyl radical produces these
      DNA lesions. It is suggested that DNA base damage arises from tert.-butyl
      hydroperoxide-mediated oxidative stress in cells, resulting in formation of
      hydroxyl radicals in close proximity to DNA. The inhibition of product formation
      at high concentrations of tert.-butyl hydroperoxide may be explained by the
      scavenging of tert.-butoxyl radical by tert.-butyl hydroperoxide resulting in
      inhibition of oxidative stress. The plausibility of the scavenging mechanism was
      evaluated with a mathematical simulation of the dose-response for DNA damage in
      solutions containing hydrogen peroxide. The simulation model predicted a bimodal
      dose-response which agreed qualitatively with the results in this study and with
      other in vivo and in vitro studies reported in the literature.

PMID- 7512202
TI  - Fluctuation test for two-stage mutations: application to gene amplification.
AB  - The determination of mutation rates is an important experimental procedure for
      characterizing mutation processes. The accepted method of determining mutation
      rates, the fluctuation test, was introduced by Luria and Delbruck in 1943. Since
      then it has been applied to various microorganisms and cells. The Luria-Delbruck
      test is based on a restrictive hypothesis of mutations being due to single
      irreversible events. However, some inherited changes in phenotype, like gene
      amplification, may be due to two or more genetic changes, some of which may be
      reversible. The Luria-Delbruck model of mutation was compared to other models
      which included reversibility and more than one mutation stage. The Luria-Delbruck
      model has been confirmed to be consistent with the original bacteriophage
      resistance data. However, for gene amplification this model gives incompatible
      estimates of mutation rates by the P0 and r methods. Relaxing the hypotheses of
      the single-stage models did not improve the fit. In contrast, a two-stage
      reversible model provided a fit. Analysis of gene amplification data by the two
      stage reversible model provides new information, including estimates of rates for
      each of the two forward stages and of the reverse step.

PMID- 7512203
TI  - Spontaneous chromosomal aberrations in cell cultures from patients with
      neurofibromatosis 1.
AB  - Neurofibroma-derived cell cultures, skin fibroblast strains from NF1 patients,
      melanocyte cultures from cafe-au-lait spots and melanocytes from skin overlying
      neurofibroma were investigated with regard to the frequencies of spontaneous
      chromosomal aberrations. A 3.4-fold increased rate of stable and unstable
      chromosome aberrations in 34 neurofibroma cultures of 18 NF1 patients was noticed
      in comparison to 17 skin biopsy-derived cultures of healthy probands. Fibroblast
      strains from the unaffected skin of nine NF1 patients revealed a 2.6-fold higher
      rate of chromosome breakage compared with the control cultures. Likewise, an
      increase of spontaneous chromosomal instability by a factor of 13.5 was found in
      cultured melanocytes from cafe-au-lait spots and by a factor of 11.9 in the skin
      melanocyte cultures of six NF1 patients in comparison to foreskin-derived
      melanocyte strains of five unaffected persons. Analyses of the distribution of
      chromatid and chromosome breaks along the chromosomes revealed a significant
      clustering of these events in the centromeric regions specifically in the four
      kinds of NF1-derived cultures.

PMID- 7512204
TI  - (E)4-[4-N,N-dimethylaminophenyl]but-3-en-2-one (DMAP) treatment inhibits the
      radiation-induced micronucleus formation in bone marrow of BALB/c mice.
AB  - The frequency of micronucleated polychromatic (MPCE) and normochromatic
      erythrocytes (MNCE) and polychromatic/normochromatic erythrocyte ratio (P/N
      ratio) was studied in the bone marrow of BALB/c mice administered with 20 mg/kg
      body weight of (E)4-[4-N,N-dimethylaminophenyl]but-3-en-2-one (DMAP), a
      phenylbutenone derivative, 30 min before exposure to different doses of 60Co
      gamma-radiation. A dose-dependent increase in the frequency of MPCE and MNCE was
      observed in double-distilled water (DDW) or oil + irradiated and DMAP +
      irradiated groups. The frequency of MPCE and MNCE was significantly less in the
      DMAP + irradiated group when compared to the DDW or oil + irradiated groups at
      all the irradiation doses studied. The P/N ratio declined with increasing
      radiation dose in DDW or oil + irradiated and DMAP + irradiated groups. The
      inhibitory effect of irradiation on the P/N ratio was less in the DMAP +
      irradiated group as compared to the DDW or oil + irradiated groups, as evidenced
      by the higher P/N ratio in the former than the latter. The P/N ratio was
      significantly higher in the DMAP + irradiated group from 1 Gy irradiation
      onwards. The dose-response relationship was linear-quadratic for MPCE, MNCE and
      P/N ratio for all the groups studied.

PMID- 7512206
TI  - Cadmium chloride induces dose-dependent increases in the frequency of micronuclei
      in mouse bone marrow.
AB  - The frequency of micronucleated polychromatic erythrocytes (MPCE) and
      normochromatic erythrocytes (MNCE) was studied in Swiss albino mice treated with
      0, 0.025, 0.05, 0.1, 0.25, 0.5, 1 and 2 mg/kg body weight of cadmium chloride. It
      was observed that cadmium chloride induced a dose-dependent increase in the
      frequency of MPCE and MNCE. However, this increase was significant only after
      treatment with 0.05 mg/kg of CdCl2 (MPCE). The polychromatic and normochromatic
      erythrocyte ratio (PCE/NCE ratio) declined with the increase in CdCl2 dose and
      this depletion was dose-dependent. A significant decline was observed only after
      0.25 mg/kg CdCl2. The dose-response relationship for all three parameters was
      linear-quadratic.

PMID- 7512205
TI  - SCE frequency of herpes simplex virus type I infected cells.
AB  - The effects of herpes simplex virus type I (HSV-I) on SCE frequencies in human
      lymphocytes in vitro were investigated. SCE frequencies in controls (mean +/- 1SD
      5.2 +/- 1.6) and in cells exposed to the virus for 3 and 6 h (mean +/- 1SD 5.3 +/
      1.6 and 5.8 +/- 1.6 respectively) were about the same. However, cells infected
      for 9 to 24 h showed a significant increase of SCE frequencies (p < 0.05).

PMID- 7512207
TI  - Possible occurrence of new mutagens with the DNA breaking activity in coffee.
AB  - Brewed and instant coffee emitted strong chemiluminescence due to singlet oxygen
      and excited carbonyls, which may be originated by the Maillard reaction of sugars
      and amino acids but not by the reaction of polyphenolics. Instant coffee cleaved
      DNA giving single-strand breaks only after it was purified by high performance
      liquid chromatography (HPLC) or by gel filtration. Retention times of
      component(s) with strong DNA breaking activity in HPLC were different from those
      of chemiluminescence emitters, although they were coeluted on a gel filtration.
      The major DNA breaking component(s) must be different from chemiluminescence
      emitters. Active oxygen radicals participated little in DNA breaking because
      active oxygen radical scavengers had only a marginal effect on DNA breaking of
      the active gel fraction. DNA breaking by the active gel fraction was inhibited by
      high concentrations of inorganic salts probably because the salts stabilized the
      DNA double strands. The active gel fraction was mutagenic to Salmonella
      typhimurium TA98 without metabolic activation. The number of His+ revertant
      colonies/g of instant coffee powder was estimated to be 4000.

PMID- 7512208
TI  - Comparison of the sites of reaction of three polycyclic aromatic hydrocarbons in
      the supF gene.
AB  - The distribution of hydrocarbon-DNA adducts through the supF gene in plasmid
      pS189 was examined using the polymerase arrest assay. For three hydrocarbon
      dihydrodiol epoxides, derived from 5-methylchrysene, 7-methylbenz[a]anthracene,
      and benzo[a]pyrene, that exhibit a preference for reaction with guanine residues
      in DNA, polymerase arrest spectra were similar but not identical. For each agent,
      guanines in different sequence contexts exhibited varying reactivities and each
      specific guanine did not necessarily respond to each agent in the same fashion.
      Thus, sequence context together with the individual dihydrodiol epoxide's
      chemical and physical properties all play a role in determining sites and extents
      of reaction within a specific gene. The polymerase arrest data were not
      predictive of the known sites of mutation hotspots for these dihydrodiol epoxides
      in the supF gene indicating that further action upon the adducted DNA by repair
      systems is probably necessary to determine which specific chemical adducts will
      ultimately give rise to mutation.

PMID- 7512209
TI  - Mutagenesis by 9-aminoacridine in Salmonella typhimurium: inhibition by glucose
      and other PTS class A carbon sources.
AB  - Reversion of the hisC3076 frameshift marker of Salmonella typhimurium has been
      measured following treatment of cells in growth and non-growth media with 9
      aminoacridine (9AA). By varying the carbon source present in a defined medium, it
      has been shown that mutagenesis is reduced close to the spontaneous level in the
      presence of glucose whilst significant reductions are also observed with
      glucosamine, mannose, mannitol, fructose or glucose 6-phosphate. Intermediate
      mutant yields are observed when lactic acid or glycerol are present, whereas any
      one of a further group of carbon sources (gluconate, arabinose, ribose, succinate
      or casein hydrolysate) permit relatively large numbers of mutants to be
      recovered. Interestingly, when any one of these "high yield" carbon sources is
      supplemented with glucose the strong inhibitory effect characteristic of glucose
      is again observed. On the basis of these results, it can be concluded that
      inhibition of 9AA-induced reversion by a carbon source is not an exclusive
      property of glucose, although when more than one carbon source is present the
      inhibitory effect of glucose predominates. Possible explanations for these
      findings include the active exclusion of 9AA from cells as a direct consequence
      of glucose transport across the cell membrane. To address this possibility, cells
      were pre-grown in verapamil, a calcium channel antagonist which is known to
      increase the mutagenicity of various 9-anilinoacridine derivatives in S.
      typhimurium. We found that glucose inhibition of 9AA-induced mutagenesis was not
      relaxed to any significant extent following treatment with verapamil. In a
      further experiment, two glucose analogues (2'-deoxyglucose and methyl-D
      glucoside) known to be actively transported into the cell but not metabolised
      past the first phosphorylation step were used. These analogues inhibit the
      transport into the cell of several types of molecules, but since they do not
      significantly depress 9AA mutagenesis it seems unlikely that blockage of 9AA
      transport across the cell membrane can be invoked to explain the inhibitory
      effect of glucose on 9AA mutagenesis. An alternative explanation based on glucose
      mediated repression of an error-prone, mutation-generating, DNA-repair process is
      presented.

PMID- 7512211
TI  - Lack of chromosomal aberration and micronucleus induction in human lymphocytes
      exposed to pulsed magnetic fields.
AB  - We exposed human peripheral blood lymphocyte cultures to 50 Hz pulsed magnetic
      fields (PMFs) in order to evaluate a possible genotoxic effect of such non
      ionizing radiation. The genotoxic effect was evaluated in terms of both
      micronucleus (MN) induction and classical chromosomal aberrations (CA); the
      mitotic index (MI) was also calculated. Khalil and Qassem (1991) found
      chromosomal and chromatid breaks and mitotic delay in human lymphocytes exposed
      for 24, 48 and 72 h to a field with characteristics similar to those used in our
      laboratory. These data are in contrast with our results previously reported in
      terms of MN induction using the cytokinesis block method (Scarfi et al., 1991).
      In this study lymphocytes from five healthy human donors were examined with the
      above mentioned tests. No genotoxic effects and increased MI were found in
      exposed samples compared to the control ones, in agreement with our previous
      results.

PMID- 7512210
TI  - The lacI transgenic mouse mutagenicity assay: quantitative evaluation in
      comparison to tests for carcinogenicity and cytogenetic damage in vivo.
AB  - The detection limit of the lacI transgenic mouse mutagenicity assay lies, in
      practice, at approximately a 50-100% increase in mutant frequency in treated
      animals over controls. The sensitivity of this assay in detecting genotoxins can
      be markedly improved by subchronic rather than acute application of the test
      compound. The lacI transgenic mouse mutagenicity assay was compared
      quantitatively to rodent carcinogenicity tests and to presently used in vivo
      mutagenicity assays. With the genotoxic carcinogens tested thus far, a rough
      correlation between mutagenic potency and carcinogenic potency was observed: on
      average, to obtain a doubling in lacI mutant frequency the mice had to be treated
      with a total dose equal to 50 times the TD50 daily dose level. This total dose
      could be administered either at a high dose rate within a few days or,
      preferably, at a low dose rate over several weeks. This analysis also indicated
      that a lacI experiment using a 250-day exposure period would give a detection
      limit approximately equal to that of a long-term carcinogenicity study. In
      comparison to the micronucleus test or the chromosome aberration assay, acute
      studies with the presently available lacI system offered no increase in
      sensitivity. However, subchronic lacI studies (3-4-month exposure) resulted in an
      increase in sensitivity over the established tests by 1-2 orders of magnitude
      (shown with 2-acetylaminofluorene, N-nitrosomethylamine, N-nitrosomethylurea and
      urethane). It is concluded that a positive result in the lacI test can be highly
      predictive of carcinogenicity but that a negative result does not provide a large
      margin of safety.

PMID- 7512213
TI  - Shuttle-vector mutagenesis by aflatoxin B1 in human cells: effects of sequence
      context on the supF mutational spectrum.
AB  - Rat-liver microsomes were used to activate aflatoxin B1 for in vitro modification
      of the pS189 shuttle vector and the related signature vector pSP189, both of
      which carry the Escherichia coli supF gene as a mutational target. Plasmid
      degradation was minimized by carrying out the in vitro incubations in the absence
      of Mg2+ ions. Modified plasmids were transfected into human Ad293 cells, then
      recovered and electroporated into E. coli MBM7070 for mutant identification.
      Point mutation frequencies for in vitro modified plasmids were dramatically
      increased over the spontaneous background level. Mutant plasmids were
      characterized by DNA-sequence analysis. The vast majority of aflatoxin B1-induced
      mutations were base substitutions, mostly G:C to T:A transversions. The spectrum
      of aflatoxin B1-induced mutations in the pS189 supF gene was very similar to that
      observed previously for the pS189 supF gene with aflatoxin B1 activated by
      cytochrome P450 1A2 (CYP1A2) synthesized from a cDNA expression vector within
      transfected Ad293 cells. However, the spectrum for pSP189, which carries the same
      supF gene as pS189, but with different surrounding sequences, exhibited some
      notable differences from that of pS189; this suggests that sequence context
      effects on mutagenic specificity can operate over distances of tens of base
      pairs.

PMID- 7512212
TI  - Dose-response relationships of micronuclei in human lymphocytes induced by
      fission neutrons and by low LET radiations.
AB  - The induction of micronuclei in cytokinesis-blocked human lymphocytes of
      different donors has been measured after G0 irradiation in vitro with a mixed
      fission neutron-gamma-ray beam, 220 kV X-rays and 60Co gamma-rays. The dose
      response relationships for the micronucleus yields were linear-quadratic for both
      types of low LET radiations. The linear model applied for neutron-induced
      micronuclei over the dose range 0-0.66 Gy. At higher doses a saturation effect
      became apparent. For neutron-induced micronucleus yields a limiting RBE value of
      12.2 was derived from the ratio of the alpha coefficients of neutrons and 60Co
      gamma-rays.

PMID- 7512214
TI  - Mechanisms of the DNA breaking activity of mutagenic 5-diazouracil.
AB  - 5-Diazouracil in monohydrated form showed mutagenicity and cytotoxicity on
      Salmonella typhimurium TA98 and TA100 strains without metabolic activation, and
      induced mouse micronucleated peripheral reticulocytes. Incubation of a plasmid
      supercoiled DNA with the compound caused DNA single-strand breaking: the
      supercoiled form was transformed into an open circular relaxed form and then into
      a linear form. The breaking was similarly caused in the absence of molecular
      oxygen. The breaking was not inhibited by superoxide dismutase and catalase, but
      inhibited by ethanol, butyl hydroxyanisole and 5,5-dimethyl-1-pyrroline N-oxide
      (DMPO), suggesting the involvement of radical species other than oxygen-derived
      radical species. Sequencing analysis of the singly 5'-end-labeled DNA fragment
      showed that the phosphodiester breaking was not site-specific. When Escherichia
      coli cells were incubated with the compound, the intracellular double-strand DNA
      was fragmented. The fragmentation was inhibited by ethanol, DMPO, N-tert.-butyl
      alpha-phenylnitrone (PBN) and thiol compounds. Generation of the carbon-centered
      radical was confirmed by the electron spin resonance spin-trapping technique
      using DMPO and PBN. The mutagenicity and the DNA breaking activity of 5
      diazouracil can be ascribed to the carbon-centered radical.

PMID- 7512216
TI  - Sister-chromatid exchanges and their distribution in human lymphocytes in
      relation to age, sex and smoking.
AB  - The effects of age, sex and smoking on sister-chromatid exchange (SCE) frequency
      and distribution in human lymphocytes were assessed by means of multiple linear
      regression. Differences in SCE scores were associated with all above variables:
      SCE increased with age and cigarette smoking intensity, and higher SCE
      frequencies were observed in females. Changes in SCE distribution were associated
      with age and smoking: the ratio of sample variance to sample mean (heterogeneity
      index) increased with age and smoking intensity. Cell proliferation kinetics, as
      measured by replication index, inversely correlated with age. Monte Carlo methods
      were used to show that in the occupational study, analysis of 20-50 persons per
      group and 25 cells per person may be recommended.

PMID- 7512215
TI  - Induction of somatic mutations in Tradescantia clone 4430 by three
      phenylenediamine isomers and the antimutagenic mechanisms of
      diethyldithiocarbamate and ammonium meta-vanadate.
AB  - Three isomers of the promutagen phenylenediamine at mM concentrations were plant
      activated and induced mutation in stamen hairs of Tradescantia clone 4430. The
      rank order of the mutagenicity of the isomers was: o-phenylenediamine > m
      phenylenediamine > p-phenylenediamine with corresponding mutagenic potencies of
      5.60, 1.43, and 0.46 mutant stamen hair cells/mumole, respectively.
      Diethyldithiocarbamate (DEDTC) and ammonium meta-vanadate (vanadate) repressed
      the mutagenic activity of o-phenylenediamine (o-PDA) in intact plants. Based on
      inhibition kinetics and reaction rates, the mechanism of DEDTC antimutagenicity
      was attributed to the inhibition of peroxidases that are required in the plant
      activation of o-PDA to mutagenic product(s). Spectrophotometric measurements of
      equimolar concentrations of o-PDA and vanadate demonstrated that the
      antimutagenic property of vanadate was mainly due to its reactivity with o-PDA.

PMID- 7512217
TI  - Quantitative structure-activity relationship (QSAR) studies in genetic
      toxicology: mathematical models and the "biological activity" term of the
      relationship.
AB  - At first sight, the QSAR issue might appear to be a mere pattern recognition
      problem; however, a purely "surface" approach to QSAR as a pattern recognition
      problem, not involving the profound plausibility of the solutions, has often been
      demonstrated to be devoid of scientific value and of predictive strength. The
      requirement for such a lateral validation should imply the recognition of the
      basic differences between the two terms of the QSAR issue: biology and chemistry.
      In particular, the difficulty to derive strong quantitative theories for the
      biological aspect of QSAR procedures should be taken into serious consideration.
      Within this conceptual framework, this paper examines the different families of
      mathematical models (classical regression, multivariate methods, neural networks)
      used in the QSAR research.

PMID- 7512218
TI  - A test for uniparental disomy in Saccharomyces cerevisiae.
AB  - Uniparental disomy is a condition in a diploid organisms where one parental
      chromosome is absent and its homolog from the other parent duplicated. It can be
      a cause of genetic somatic disease in mammals because of imprinting. Imprinting
      creates a sex-specific pattern of epigenetic gene inactivation at least in
      mammals and, consequently, a complete set of both maternal and paternal
      chromosomes is required for normal development. Moreover, it has been shown for
      several types of tumors that recessive tumor alleles originally present in a
      heterozygous condition in normal somatic tissue have become homozygous in the
      tumor cells. Homozygosity is frequently caused by uniparental disomy. A similar
      situation is found in Saccharomyces cerevisiae where the spontaneous or induced
      expression of linked recessive alleles flanking a common centromere is
      preponderantly due to isodisomy where one of the homologs is lost and the
      retained homolog duplicated. In contrast to the situation in Aspergillus
      nidulans, isodisomy does not appear to be caused by two sequential and
      independent events of malsegregation resulting first in an unstable trisomic
      condition from which a normal disomic condition is restored through segregational
      loss of one supernumerary chromosome. Rather, an as yet unknown mechanism seems
      to directly generate isodisomy and thus Saccharomyces cerevisiae could provide a
      short-term test for the detection of this type of genetic change.

PMID- 7512220
TI  - Mouse dominant lethal and sperm abnormality studies with combined exposure to X
      rays and mitomycin C.
AB  - The induction of dominant lethal effects and sperm abnormalities in Pzh:Swiss
      male mice after treatments with X-rays and mitomycin C (MMC) was investigated.
      Combinations of high (1.00 Gy + 5.25 mg/kg bw MMC) and low (0.25 Gy + 1.75 mg/kg
      bw MMC) doses of both agents were used. Exposure to high doses of X-rays + MMC
      induced an increased rate of dominant lethal mutations in spermatogonia and late
      spermatocytes. Combined treatment with low doses of X-rays and MMC was not
      mutagenic in any stage of spermatogenesis. MMC increased the frequency of
      abnormal spermatozoa after exposure alone and in combination with X-rays.
      Treatment with two high doses (1.00 Gy + 5.25 mg/kg bw MMC) induced 58.4%
      abnormal spermatozoa. After combined exposure to low doses of both agents 35.7%
      spermatozoa with malformations were observed.

PMID- 7512219
TI  - Chromosome aberrations in nuclear power plant workers: the influence of dose
      accumulation and lymphocyte life-time.
AB  - Chromosome analyses were performed in blood lymphocytes of 22 nuclear power plant
      workers with a mean accumulated radiation dose of 390 mSv (270-530 mSv). Nineteen
      workers had received 300 mSv 4-16 years prior to sampling. The frequency of
      dicentrics and ring chromosomes (1.75 x 10(-3)) was significantly elevated as
      compared to a control group (0.58 x 10(-3)). Based on the initial slope of an in
      vitro 60Co gamma-ray curve, a biological dose estimate of only 110 mSv was
      derived. This can be interpreted in terms of an "equivalent-acute" dose at the
      time of blood sampling which can be derived by weighting annual doses during
      working periods of 12-30 years for a mean life-time m of lymphocytes. The annual
      doses were additionally weighted for a uniform distribution during a whole year.
      Using m = 10 years, a mean "equivalent-acute" dose of 90 mSv (64-157 mSv) is
      obtained, which compares more closely to the biologically estimated dose than 20
      mSv (7-71 mSv) based on m = 4.3 years.

PMID- 7512221
TI  - Human cell clones, RSa and UVr-1, differing in their capability for UV-induced
      virus reactivation and phenotypic mutation.
AB  - UVr-1 is a human cell clone established as a variant with increased resistance to
      cell killing by ultraviolet light (UV, principally 254 nm wavelength) from a UV
      sensitive cell clone, RSa. Both cells have been characterized to have much the
      same capacity of UV-induced DNA repair synthesis in whole cells, and the parent
      RSa cells were recently found to be hypermutable. In the present study UVr-1
      cells were characterized in comparison RSa cells with respect to UV-induced virus
      reactivation and phenotypic mutation. Survival levels of UV-irradiated vaccinia
      virus and herpes simplex virus type 1 (HSV-1) were much the same in
      logarithmically proliferating UVr-1 and RSa cells. Correlated with these host
      cell reactivation levels, the same extent of UV-induced DNA repair replication
      synthesis was observed in isolated nuclei of the two cell clones. Enhancement of
      survival levels of UV-irradiated HSV-1 was detected when proliferating RSa cells
      were irradiated with UV prior to the virus infection. In contrast, this enhanced
      virus reactivation (EVR) was not detected in similarly irradiated and infected
      UVr-1 cells. As for phenotypic mutation frequencies assessed by the cloning
      efficiency of cells with increased resistance to ouabain cell killing (OuaR),
      OuaR mutants were not obtained from UVr-1 cells either with or without UV
      irradiation. When the proliferation of cells was synchronized, both EVR and OuaR
      mutations were detected in RSa cells irradiated with UV at any cell cycle phase,
      being greatest in the later half of the G1 phase. However, there was no
      detectable EVR or mutation in any phase of synchronous UVr-1 cells. The
      hypomutability of UVr-1 cells and hypermutability of RSa cells in a G1 cell cycle
      phase was also found even if 4-nitroquinoline 1-oxide was used as a mutagen or
      mutant cells with increased resistance to 6-thioguanine cell killing were
      estimated.

PMID- 7512222
TI  - Structure of the regulatory domains of the Src-family tyrosine kinase Lck.
AB  - The kinase p56lck (Lck) is a T-lymphocyte-specific member of the Src family of
      non-receptor tyrosine kinases. Members of the Src family each contain unique
      amino-terminal regions, followed by Src-homology domains SH3 and SH2, and a
      tyrosine kinase domain. SH3 and SH2 domains mediate critical protein interactions
      in many signal-transducing pathways. They are small, independently folded modules
      of about 60 and 100 residues, respectively, and they are often but not always
      found together in the same molecule. Like all nine Src-family kinases (reviewed
      in ref. 3), Lck is regulated by phosphorylation of a tyrosine in the short C
      terminal tail of its catalytic domain. There is evidence that binding of the
      phosphorylated tail to the SH2 domain inhibits catalytic activity of the kinase
      domain and that the SH3 and SH2 domains may act together to effect this
      regulation. Here we report the crystal structures for a fragment of Lck bearing
      its SH3 and SH2 domains, alone and in complex with a phosphotyrosyl peptide
      containing the sequence of the Lck C-terminal regulatory tail. The latter complex
      represents the regulatory apparatus of Lck. The SH3-SH2 fragment forms similar
      dimers in both crystals, and the tail peptide binds at the intermolecular SH3/SH2
      contact. The two structures show how an SH3 domain might recognize a specific
      target and suggest how dimerization could play a role in regulating Src-family
      kinases.

PMID- 7512225
TI  - Theoretical and experimental assessment of the kinetic properties of N-isopropyl
      p-[123I]iodoamphetamine in the human brain.
AB  - The effect of the loss of radioactivity from the human brain on the measurement
      of regional cerebral blood flow (rCBF) using N-isopropyl-p-[123I]iodoamphetamine
      (IMP) was evaluated by measuring rCBF in 10 normal male volunteers from 0.5 to 30
      minutes after intravenous administration. rCBF was calculated by the operational
      equation, which assumes no product loss. Brain tissue and arterial blood
      concentration data were plotted according to a multiple-time/graphic evaluation
      technique. Data were fitted to the kinetic three-compartment model to estimate
      four kinetic rate constants to evaluate activity loss from the brain. These
      studies showed that loss of activity from the brain is negligible during the
      first 5 minutes, but after 7.5 minutes the loss becomes significantly higher with
      time. The present study corroborates the necessity for using single photon
      emission computed tomographic images measured within 5 minutes of IMP injection
      to quantify rCBF.

PMID- 7512223
TI  - [Nitric oxide: a new light on many clinical syndromes].

PMID- 7512224
TI  - Evaluation of masked neurological disorders in the chronic stage after middle
      cerebral artery occlusion in rats--methamphetamine-induced rotation and regional
      glucose metabolism in basal ganglia.
AB  - Neurofunctional changes in rats in the chronic stage of focal cerebral ischemia
      induced by left middle cerebral artery (MCA) occlusion were examined.
      Neurological disorders and behavioral changes were observed with or without
      methamphetamine administration. Metabolic changes in the basal ganglia following
      methamphetamine intraperitoneal injection were evaluated by [14C]deoxyglucose
      autoradiography 30 days after occlusion. Neurological examination revealed
      persistent spontaneous rotation to the lesioned side in two of 18 rats, and
      forelimb flexion to the lesioned side in nine of 18 rats during a 28-day
      observation period after occlusion. Intraperitoneal administration of
      methamphetamine (4 mg/kg) induced full 360 degrees rotation toward the lesion
      side in 14 of 17 rats. The number of rotations was inversely correlated with the
      size of the intact striatum on the lesion side, especially in rats with cerebral
      infarct located only in the striatum. Rats with extensive cortical lesion in
      addition to striatal lesion did not demonstrate this relationship. Deoxyglucose
      autoradiography in methamphetamine-untreated rats showed symmetrical local
      cerebral glucose utilization in the basal ganglia except for the subthalamic
      nucleus, striatum and sensorimotor cortex. Autoradiography in methamphetamine
      treated and MCA-occluded rats showed a remarkable increase in glucose utilization
      in the anterior striatum, entopeduncular nucleus, substantia nigra pars
      reticulata, and sensorimotor cortex contralateral to the occlusion side, but not
      on the lesioned side. Rotational movements observed in methamphetamine-treated
      rats are related to lack of stimulation of the basal ganglia system on the
      ischemic side.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512226
TI  - Clinical application of angioscopy during carotid endarterectomy for patients
      with internal carotid artery stenosis.
AB  - The accuracy of angioscopy in detecting atherosclerotic changes, such as plaque,
      ulcer, and mural thrombus, in the extracranial cerebral arteries was evaluated
      during carotid endarterectomy by comparison with angiographic and operative
      findings. Ten patients with internal carotid artery stenosis underwent
      intraoperative angioscopy during surgery. After clamping the carotid bifurcation,
      intra-arterial atherosclerotic lesions were observed with an angioscope (0.8 or
      1.4 mm outer diameter) inserted through a small incision in the common carotid
      artery. Angioscopic findings correlated well with both angiographic and operative
      findings in six patients, and provided additional information in two patients,
      such as organized thrombi within the ulcer and mural thrombi. Angioscopic
      findings were quite different to those from angiograms in two patients. In one,
      an ulcer on angiograms was false positive, and in the other, false negative.
      These findings were confirmed intraoperatively. Our results suggest that
      preoperative carotid angioscopy is of great value in detecting ulcers more
      accurately than angiography, and in selecting candidates for carotid
      endarterectomy, although further development of equipment is needed.

PMID- 7512227
TI  - Efficacy of superficial temporal to middle cerebral artery anastomosis against
      hemodynamic stroke.
AB  - The effect of superficial temporal artery-middle cerebral artery anastomosis on
      regional cerebral blood flow (rCBF) was measured on 31 patients with ischemic
      cerebrovascular diseases. rCBF was measured on the precentral and superior
      temporal gyri during surgery using the thermal diffusion technique. The mean rCBF
      was significantly lower than controls before anastomosis, but increased
      significantly after. Severer clinical symptoms were associated with lower rCBF.
      The rCBF increased significantly in patients with transient ischemic attack,
      reversible ischemic neurological deficit, and minor and major completed stroke.
      All 31 patients demonstrated dysautoregulation, both before and after
      anastomosis. However, the rCBF had increased above the ischemic threshold during
      hypotension, achieving a reserve capacity to prevent hemodynamic stroke.

PMID- 7512228
TI  - Neuropsychological outcome and social recovery of head-injured patients.
AB  - The Wechsler Adult Intelligence Scale and Yatabe-Guilford personality test were
      administered to 123 patients hospitalized for head injury who had made a
      relatively good recovery. Intelligence quotient (IQ) was correlated with clinical
      condition based on the Glasgow Coma Scale and duration of coma. More severely
      injured patients tended to show a greater decline in IQ. The type of lesion, as
      described by computed tomography, was also an important factor in predicting the
      outcome of intellectual function. The mean IQ of patients with diffuse injury,
      such as diffuse axonal injury and diffuse brain swelling, and intracerebral
      hematoma, was significantly lower than that of the control subjects, especially
      performance IQ (PIQ). Several patients demonstrated improved IQ level during the
      initial year. In particular, PIQ improved more than verbal IQ. The difference
      between the IQ of patients achieving social recovery and not was significant (p <
      0.001). Causes of difficulty in returning to previous work were decreased IQ and
      personality change, such as lack of cooperativeness. Neuropsychological
      evaluation is important in predicting social recovery and selecting necessary
      neuropsychological rehabilitation.

PMID- 7512230
TI  - Asymptomatic syringomyelia associated with cerebellopontine angle meningioma-
      case report.
AB  - A 66-year-old female with a 3-year history of left trigeminal neuralgia presented
      with an unusual left cerebellopontine angle meningioma associated with
      asymptomatic syringomyelia at the C2 to C4 levels diagnosed by magnetic resonance
      (MR) imaging. Two months after total tumor removal, the syringomyelia had
      diminished without shunting. MR images are useful as a basis for early diagnosis
      of syringomyelia.

PMID- 7512229
TI  - Treatment of severe localized cerebral vasospasm following recurrent hemorrhage
      from middle cerebral artery aneurysm--case report.
AB  - A 52-year-old female presented with localized but severe cerebral vasospasm
      induced by recurrent aneurysmal subarachnoid hemorrhage. The middle cerebral
      artery (MCA) aneurysm was clipped and the subarachnoid hematoma evacuated 1 day
      after recurrent hemorrhage. The cerebral vasospasm, localized in a region near
      the MCA aneurysm, was reduced by papaverine and nicardipine vasodilating agents
      delivered via an Ommaya cerebrospinal fluid reservoir placed at craniotomy.

PMID- 7512231
TI  - Pineocytoma with intratumoral hemorrhage following ventriculoperitoneal shunt-
      case report.
AB  - A 58-year-old female with pineocytoma developed intratumoral hemorrhage after
      ventriculoperitoneal shunting for hydrocephalus. Neurological examination
      revealed Parinaud's sign and papilledema. Computed tomography and magnetic
      resonance (MR) imaging revealed a pineal neoplasm and obstructive hydrocephalus.
      Serum and cerebrospinal fluid levels of human chorionic gonadotropin, alpha
      fetoprotein, carcinoembryonic antigen, and placental alkaline phosphatase were
      negative or within normal limits. MR images after the ventriculoperitoneal
      shunting disclosed intratumoral hemorrhage and markedly smaller ventricles. The
      tumor was totally removed via the occipital transtentorial approach and was
      diagnosed histologically as a pineocytoma with astrocytic differentiation. The
      tumor probably shifted away from the surrounding structures following the marked
      reduction in ventricular size after ventriculoperitoneal shunting, resulting in
      changed venous circulation in the tumor and the formation of intratumoral
      hematoma.

PMID- 7512232
TI  - Cranial metastasis of hepatocellular carcinoma in a female--case report.
AB  - A 78-year-old female presented with swelling and severe pain in the left forehead
      secondary to a simple head injury received 1 month previously. On admission,
      neurological examination was normal. Plain skull x-ray films and computed
      tomography showed an osteolytic and well-defined mass in the left frontal bone.
      Bone scintigraphy showed high-uptake areas in the right lower ribs and fifth
      lumbar vertebra. Blood tests showed slight liver dysfunction and a high alpha
      fetoprotein level. Abdominal computed tomography showed a huge mass within the
      liver. Left common carotid angiography disclosed the enlargement of several
      feeding arteries arising from the external carotid artery with tumor staining.
      The bone tumor was removed for histological diagnosis and to reduce the localized
      pain. The histological diagnosis was a cranial metastasis from hepatocellular
      carcinoma. She died of ruptured varicose veins of the esophagus approximately 8
      months after surgery. Surgery for cranial metastasis from hepatic cancer is only
      indicated when localized pain or hemorrhage threaten the quality of life.

PMID- 7512233
TI  - Dandy-Walker syndrome forming a giant occipital meningocele--case report.
AB  - A boy was born with Dandy-Walker syndrome associated with a giant occipital
      meningocele, cleft lip, and cleft palate. The meningocele was actually a
      component of the giant posterior fossa cyst which communicated with the fourth
      ventricle. A cyst-peritoneal shunt achieved a considerable decrease in the size
      of the meningocele, but decubital ulcers developed due to restricted head
      movement caused by the occipital lesion. Cranioplasty removed a wide area of the
      inferior occipital bone, and the boundary between the superior occipital and
      parietal bones was thinned to allow free bending of the bone flap. The
      meningocele was removed totally in the third operation, but infection of the
      wound and pneumonia developed, causing death. The coexistence of Dandy-Walker
      syndrome and occipital meningocele, together with midline facial anomalies, may
      suggest a later pathogenesis of Dandy-Walker syndrome than previously believed.

PMID- 7512235
TI  - Pharmacological modulation of endogenous dopamine and DOPAC outflow from nucleus
      accumbens.
AB  - The release of endogenous DA and DOPAC from nucleus accumbens slices were studied
      measuring net outflow of DA and DOPAC in the superfusate of static chambers, to
      analyze the correlation between DA and DOPAC outflows and identify which DA
      stores may serve as possible sources for DOPAC formation. Under resting
      conditions, or following stimulation with low (< 15 mM) KCl concentration, DOPAC
      outflow was greater than DA. When DA release was stimulated by higher (> 25 mM)
      KCl concentrations, DA outflow increased, proportionally more than DOPAC. In the
      virtual absence of Ca2+ in the Krebs solution DA outflow, induced by 25 mM KCl,
      was reduced to about 10%, while DOPAC outflow was only reduced to 45%. When the
      synthesis of DA was inhibited with alpha-MPT, DA and DOPAC outflow were unchanged
      during the first stimulation period. During a second stimulation period, however,
      their outflow were significantly reduced. Nomifensine, a DA uptake inhibitor,
      increased the basal DA outflow by about 100%, but only blocked DOPAC basal
      outflow by about 25%. The 25 mM KCl stimulated DA outflow was not affected by
      Nomifensine, while the stimulated DOPAC outflow was reduced by about 50%. These
      results demonstrate that there is a weak correlation between the outflows of DA
      and DOPAC, suggesting a complex relationship between the mobilization of the
      different DA pools and DOPAC outflow. The formation of DOPAC from some of these
      pools, appear to be dependent on the stimulation levels and on the
      pharmacological manipulation of the tissue.

PMID- 7512234
TI  - Metabotropic glutamate receptor modulation of cAMP accumulation in the neonatal
      rat hippocampus.
AB  - The pharmacology and cellular mechanism by which metabotropic glutamate receptor
      (mGluR) activation modulates cAMP formation was studied in cross-chopped
      hippocampal slices from neonatal (7 day old) rats. The selective mGluR agonist
      1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), and other non
      selective mGluR agonists produced concentration-related stimulation of basal cAMP
      formation in this tissue. The relative agonist potency order was 1S,3R-ACPD =
      quisqualate > ibotenate >> 1R,3S-ACPD. 1S,3R-ACPD stimulated cAMP accumulation
      was antagonized in a stereoselective manner by L-2-amino-3-phosphonopropionate (L
      AP3), but not by higher chain homologues such as L-2-amino-4-phosphonobutyrate (L
      AP4) and 2-amino-5-phosphonopentanoate (AP5). 1S,3R-ACPD-enhanced cAMP formation
      was greatly inhibited by incubation with adenosine deaminase. In the adult rat
      hippocampus, 1S,3R-ACPD did not appreciably increase basal cAMP, but inhibited
      forskolin-stimulated cAMP formation, and this effect was observed with or without
      adenosine deaminase. In the presence of the adenosine receptor antagonist and
      cAMP phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX), 1S,3R-ACPD
      did not enhance cAMP formation in the neonatal hippocampus, but inhibited
      forskolin-stimulated cAMP (like in the adult tissue). These results demonstrate
      that mGluRs that increase cAMP in the neonatal hippocampus have a unique
      pharmacology when compared to mGluRs that decrease cAMP accumulation and increase
      phosphoinositide hydrolysis. 1S,3R-ACPD stimulation of cAMP in the neonatal rat
      hippocampal slice involves potentiation of responses to endogenous adenosine.
      Negatively coupled cAMP linked mGluRs are also present in the neonatal tissue,
      but are masked by the predominance of the positively coupled mGluR cAMP response.

PMID- 7512236
TI  - The actions of phenylglycine derived metabotropic glutamate receptor antagonists
      on multiple (1S,3R)-ACPD responses in the rat nucleus of the tractus solitarius.
AB  - The effects of the metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] and a series of
      phenylglycine-derived putative mGluR antagonists were examined on
      electrophysiological responses mediated by glutamate and GABA receptors in the
      nucleus of the tractus solitarius (NTS) in transverse brainstem slices of the
      rat. Monosynaptic excitatory currents (EPSC's) evoked by electrical stimulation
      in the region of the tractus solitarius (TS) were reduced in the presence of
      (1S,3R)-ACPD in > 90% of neurons recorded in the dorsomedial subdivision of the
      NTS adjacent to the area postrema (AP). Monosynaptic evoked inhibitory currents
      (IPSC's) were similarly inhibited by (1S,3R)-ACPD. The inward current evoked by
      pressure application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid
      (IAMPA) was potentiated in the presence of (1S,3R)-ACPD, whereas the outward
      current evoked by the gamma-amino-butyric acid-A (GABA-A) receptor agonist
      muscimol (IMUSC) was inhibited. (1S,3R)-APCD also produced a postsynaptic inward
      current (IK(ACPD)) associated with a decrease in membrane conductance in
      approximately 50% of cells. The novel mGluR antagonists (S)-4-carboxy-3-hydroxy
      phenylglycine (4C3H-PG), (R,S)-4-carboxy-phenylglycine (4C-PG) and (R,S)-alpha
      methyl-4-carboxy-phenylglycine (alpha M4C-PG) reversibly antagonized the effects
      of (1S,3R)-ACPD on EPSC's IPSC's, IAMPA and IMUSC. The first two compounds also
      displayed weak agonist activity. However, none of the antagonists significantly
      inhibited IK(ACPD) at concentrations which blocked (1S,3R)-ACPD effects on
      synaptic transmission. These results suggest that pharmacologically distinct
      mGluR's may be present in the NTS.

PMID- 7512238
TI  - Comparative analysis of ionic currents in the somatic membrane of embryonic and
      newborn rat sensory neurons.
AB  - Inward currents in the somatic membrane of dissociated rat dorsal root ganglion
      neurons have been studied in two groups of animals (17 days of embryonic
      development and the first day after birth) by suction pipette (whole-cell
      configuration) and voltage-clamp techniques. Altogether 157 neurons were
      examined. Four components in the inward currents have been identified: fast
      tetrodotoxin-sensitive (INaf) and slow tetrodotoxin insensitive (INas) sodium,
      low-(ICal) and high-threshold (ICah) calcium currents. The percentage of neurons
      demonstrating four types of inward currents INaf, INas, ICal, ICah increased from
      21% in embryo to 61% in newborn. The percentage of neurons with INaf, INas and
      ICah increased from 4% in embryonic to 14% in the first day after birth. The
      percentage of cells with INaf, ICal and ICah (without tetrodotoxin-insensitive
      INas) decreased from 56 to 11% in embryo and newborn rats, respectively. A
      statistically significant linear correlation was found between the densities of
      INaf and ICah currents for both ages. A correlation also occurred between the
      densities of INas and ICah. A reciprocal relation between the densities of both
      types of calcium currents and the size of cell soma was found in the neurons with
      all four types of inward currents from newborn animals. A comparison of these
      data with previous study of inward currents during postnatal development
      indicates that the most dramatic changes in their distributions and mean
      densities takes place some time after the birth of the animals.

PMID- 7512237
TI  - Reduced sciatic nerve substance P and calcitonin gene-related peptide in rats
      with short-term diabetes or central hypoxaemia co-exist with normal messenger RNA
      levels in the lumbar dorsal root ganglia.
AB  - Endoneurial hypoxia of ischaemic origin is believed to cause the reduction in
      sciatic nerve substance P levels in experimentally diabetic rats. The first part
      of this study was designed to determine whether the changes seen extended to
      another neuropeptide, calcitonin gene-related peptide, and to reveal any
      correlation between substance P and calcitonin gene-related peptide levels in the
      sciatic nerve of both diabetic and centrally hypoxaemic rats. Comparison of
      streptozotocin diabetic rats (four-week duration) with their control group showed
      clear reductions in both substance P-like immunoreactivity (control = 225 +/- 20
      pg/mg protein, diabetic = 139 +/- 19; P < 0.01) and calcitonin gene-related
      peptide-like immunoreactivity (control = 9.08 +/- 0.65 ng/mg protein, diabetic =
      4.43 +/- 0.44; P < 0.001). A similar pattern was seen with the comparison of five
      week centrally hypoxaemic rats (housed in 10% O2) with their controls for both
      substance P-like immunoreactivity (control = 222 +/- 10 pg/mg protein, hypoxic =
      148 +/- 13; P < 0.001) and calcitonin gene-related peptide-like immunoreactivity
      (control = 6.58 +/- 0.42 ng/mg protein, hypoxic = 3.01 +/- 0.45; P < 0.001).
      Calcitonin gene-related peptide levels correlated closely with substance P levels
      in both the diabetes and central hypoxaemia studies (r2 = 0.69 and 0.62,
      respectively). The second part of this study measured the messenger RNA levels of
      the substance P precursor, preprotachykinin-A, and calcitonin gene-related
      peptide messenger RNA in the L4 and L5 dorsal root ganglia of control, diabetic
      and centrally hypoxaemic rats. There was no change in preprotachykinin-A or
      calcitonin gene-related peptide messenger RNA levels between any of the groups,
      suggesting that the sciatic nerve decreases in substance P and calcitonin gene
      related peptide described above are post-transcriptional in origin.

PMID- 7512239
TI  - Changes in the serotonergic system during the sleep-wake cycle: simultaneous
      polygraphic and voltammetric recordings in hypothalamus using a telemetry system.
AB  - Changes in the serotonergic system in the posterior hypothalamus of freely moving
      rats were related to sleep and wakefulness using in vivo voltammetry (with carbon
      fiber microelectrodes) and polygraphic recordings. By using an optoelectronic
      telemetry system for the voltammetric signals, electrical cross-talk between the
      two settings was avoided and simultaneous neurochemical and electro-physiological
      recordings could be made so that a detailed time course of events could be
      obtained. Extracellular levels of the serotonin metabolite, 5-hydroxy
      indoleacetic acid, measured every 2 min, increased with wakefulness and decreased
      with sleep: levels were significantly lower during desynchronized sleep than slow
      wave sleep. In vivo voltammetry associated with the optoelectronic telemetry
      system appears to be a useful tool for studying the relationship between
      neurochemical changes and electrophysiological events.

PMID- 7512240
TI  - Mapping of perineuronal nets in the rat brain stained by colloidal iron hydroxide
      histochemistry and lectin cytochemistry.
AB  - Net-like structures, visualized with the Golgi technique and several
      histochemical and immunocytochemical methods, have been described to ensheath
      somata, parts of dendrites and axon initial segments of various types of neurons.
      The origin and function of these perineuronal nets have been controversially
      discussed. Recently, it was confirmed that they are glia-associated. In the
      present study such perineuronal nets were demonstrated by using colloidal iron
      hydroxide staining for detection of polyanionic components and the plant lectins
      Vicia villosa agglutinin and Wisteria floribunda agglutinin with affinity for N
      acetylgalactosamine. This paper shows their distribution patterns and the
      occurrence of regional specialization of these nets which might provide a basis
      to suggest functional implications of these structures. Perineuronal nets were
      found in more than 100 brain regions, such as neocortex, hippocampus, piriform
      cortex, basal forebrain complex, dorsal lateral septal nucleus, lateral
      hypothalamic area, reticular thalamic nucleus, zona incerta, deep parts of
      superior and inferior colliculus, red nucleus, substantia nigra, some tegmental
      nuclei, cerebellar nuclei, dorsal raphe and cuneiform nuclei, central gray,
      trochlear nucleus, pontine and medullar reticular nuclei, superior olivary
      nucleus and vestibular nuclei. Neurons enwrapped by perineuronal nets not only
      differ in morphology but also in transmitter content. In neocortical and
      hippocampal regions there occurs a much higher number of perineuronal nets
      ensheathing non-pyramidal cells than in paleocortical structures. Most
      subcortical regions containing perineuronal nets were found to be integrated in
      motor functions. The findings are discussed with respect to known
      electrophysiological data of cell types described in our investigation as net
      associated. There are some indications that such cells may represent fast firing
      types.

PMID- 7512242
TI  - Brief-lifetime, fast-inactivating ion channels account for the alpha-bungarotoxin
      sensitive nicotinic response in hippocampal neurons.
AB  - Single-channel currents underlying the various types of nicotinic receptor-gated
      whole-cell currents (previously termed IA, IB, II and III) were identified in rat
      hippocampal neurons. In response to applied acetylcholine (ACh), most of the
      neurons showed a fast-decaying whole-cell current (type IA) that can be blocked
      by alpha-bungarotoxin (alpha-BGT). In these neurons, a novel nicotinic receptor
      channel was found, having a conductance of 73 pS and an open time of 0.12 ms at 
      80 mV. This channel showed a fast concentration-dependent inactivation that had a
      time constant of 0.5 ms at 1 mM ACh. A high Ca2+ permeability and the involvement
      of alpha 7 receptor subunits in the channel structure were suggested.

PMID- 7512241
TI  - Deafferentation induces early and delayed differential changes in the pattern of
      expression of the various guanine nucleotide binding protein mRNAs in rat
      striatum.
AB  - A polymerase chain reaction-derived method was used to identify and quantitate
      the relative abundance of the different mRNAs encoding various isoforms of the
      guanine nucleotide regulatory protein Gs, Gi, and Go alpha subunits in the
      striata of rats unilaterally injected with 6-hydroxydopamine in the substantia
      nigra. Thirty days after the lesion, the mRNA levels of the G(o) and of the Gi 1
      alpha subunits were increased by about 2-3 times, those of the Gi 3 decreased by
      about 60% and those of Gi 2 and Gs unmodified. The pattern of expression of the
      G(o) alpha subunits mRNA changed in a time-dependent fashion, being significant
      20 days after the lesion. The decrease in Gi 3 alpha subunit mRNA levels was
      maximum 10 days after the lesion and tended to be reduced in magnitude with time
      while the changes in Gi 1 alpha subunit mRNA showed a byphasic behaviour being
      reduced at 10 days and increased at 30 days after the lesion. These data suggest
      that the expression of the various G protein alpha subunits in the striatum are
      continuously regulated by factors originating from afferent neurons and
      surrounding cells.

PMID- 7512244
TI  - Anxiolytic-like action of centrally administered galanin.
AB  - The neuropeptide galanin is present in limbic brain areas important for
      emotionality. We examined whether central galanin may be involved in mechanisms
      of anxiety. Rats were tested in a pharmacologically validated animal model of
      anxiety, the Vogel punished drinking test. A 100% increase of punished responding
      was seen after 3 nmol galanin i.c.v. After 15 nmol, signs of sedation were seen,
      and no increase of punished responding could be observed. Drinking motivation,
      shock thresholds and exploratory locomotor activity were not affected by 3 nmol
      galanin. These results support a specific anxiolytic-like action of galanin,
      similar to that of the functionally related peptide, neuropeptide Y.

PMID- 7512243
TI  - Neurotrophic effects of substance P on hippocampal neurons in vitro.
AB  - The potential neurotrophic effect of substance P-like immunoreactivity present in
      culture media was assessed in rat embryonic day 18 hippocampal cultures. The
      neurokinin-1 (substance P) receptor antagonist CP-96345 induced neurotoxicity
      that was dose dependent and attenuated by addition of substance P or the
      neurokinin-1 agonist [Sar9,Met(O2)11]-SP. These studies suggest that under some
      conditions neurokinin-1 receptor stimulation promotes neuronal survival.

PMID- 7512245
TI  - The major pelvic ganglion is the main source of nitric oxide synthase-containing
      nerve fibers in penile erectile tissue of the rat.
AB  - The possible implication of nitric oxide synthase (NOS) in penile erection was
      examined by utilizing NADPH histochemistry in the rat. NADPH histochemistry
      indicated that the major pelvic ganglion (MPG), a well-known origin of nerve
      fibers supplying the external genitalia, contained many NOS-positive neurons. On
      the other hand, NOS-positive nerve fibers in penile erectile tissue observed in
      the walls of both arteries and veins, as well as in intrinsic smooth muscles. The
      retrograde tracing study with Fluoro-Gold (FG) in combination with NADPH
      histochemistry revealed that almost all MPG neurons which were retrogradely
      labeled with FG injected into the penile crura were NOS-positive. Thus, the MPG
      was considered to be the main source of NOS-positive nerve fibers in penile
      erectile tissue.

PMID- 7512248
TI  - Redistribution of K+ channels into dendrites is unlikely to account for
      developmental down regulation of A-currents in rat dentate gyrus granule cells.
AB  - The electrical reactions of many central neurons depend on two voltage-activated
      K+ currents: the fast transient A-current IA and the delayed rectifier current
      IK. In rat dentate gyrus granule cells, the A-current density decreases during
      ontogenesis, possibly due to a redistribution of K+ channels from somata into
      dendrites. We tested this possibility in mechanically isolated granule cells with
      preserved dendrites of different length. Potassium currents were recorded with
      the whole-cell patch-clamp technique using prepulse protocols with and without a
      delay interval to isolate IA. A correlation between the length of the dendrites
      and the amount of A-current expressed in a given cell could not be demonstrated.
      Our findings therefore confirm an ontogenetic down regulation of A-currents.

PMID- 7512246
TI  - The injury response of pulpal NPY-IR sympathetic fibers differs from that of
      sensory afferent fibers.
AB  - Light microscopic immunocytochemistry demonstrated that neuropeptide Y (NPY)
      containing sympathetic fibers in rat molars did not change morphology or staining
      characteristics after pulp exposure injury. This result, in combination with
      recent findings concerning NGF synthesis in injured pulp and NGF-receptor
      localization on pulpal sensory fibers, suggests that small diameter sensory
      fibers in pulp may be under NGF control, but NPY containing sympathetic efferent
      fibers are not. Thus, sympathetic fibers in tooth pulp have a different response
      to NGF compared to those in many other tissues.

PMID- 7512247
TI  - Sensorimotor cortex projections to the ventrolateral and the dorsomedial medulla
      oblongata in the rat.
AB  - After small pressure injections of Fluorogold (FG), and Dextran
      tetramethylrodamine (DR) into the dorsal motor nucleus of the vagus/nucleus of
      the solitary tract (DMV/NTS) and the rostral ventrolateral medulla (RVLM),
      respectively, retrograde FG-labelled cells were found mainly in the sensorimotor
      cortex; retrograde DR-labelled cells were located in the same cortical areas and
      in the prefrontal cortex. Double-labelled cells were also found in the
      sensorimotor cortical areas. These results provide evidence of direct projections
      from the sensorimotor cortex to the DMV/NTS and RVLM and suggest that somatic
      cortical areas directly control cardiovascular output during sensory and somatic
      processes.

PMID- 7512249
TI  - Interferon-gamma and interleukin-1 beta induce nitric oxide formation from
      primary mouse astrocytes.
AB  - An inducible form of nitric oxide synthase (iNOS) capable of producing large
      quantities of nitric oxide (NO) exists in some cell types. We demonstrate by
      immunoprecipitation and nitrite formation that interleukin-1 beta (IL1 beta) plus
      interferon-gamma (INF gamma) induce the expression of nitric oxide synthase in
      primary cultures of murine cortical astrocytes. This induction is time and dose
      dependent, and inhibited by the NOS inhibitor NG-nitro-L-arginine and the protein
      synthesis inhibitor cycloheximide.

PMID- 7512250
TI  - Substance P innervation of equine synovial membranes: joint differences and
      neural and nonneural receptor localizations.
AB  - Substance P (SP) immunocytochemistry and receptor autoradiography were used to
      define the innervation of the equine synovial membrane of joints equivalent to
      the wrist and knuckle of man. SP-immunoreactive fibers were mainly concentrated
      around blood vessels in the subsynovial layer, although not exclusively, while in
      the more distal joint, SP fibers were more frequently seen in the synovial
      surface layer. Iodinated SP receptor autoradiography studies revealed silver
      grain concentrations in the advential layer of blood vessels associated with the
      vasa vasorum, on the vascular endothelium and in the synovial surface. These
      findings suggest that SP has various sites of action within the synovial
      membrane, each of which may contribute both a sensory function and a different
      component of the inflammatory process to the joint.

PMID- 7512251
TI  - Developmental change in the modulation of acetylcholine receptor channel by
      protein kinase C activation in Xenopus embryonic muscle cells.
AB  - Protein phosphorylation is important in synaptic transmission and plasticity. We
      report here that phorbol 12-myristate 13-acetate (TPA), a protein kinase C (PKC)
      activator, enhances the postsynaptic response at developing neuromuscular
      junctions by increasing the open time of embryonic acetylcholine (ACh) channels
      at earlier stages of cultured myocytes. Compared with day-1 cultures, the effects
      of TPA declined or disappeared on day-3 cultures. Adenosine 5'-triphosphate (ATP)
      which is co-stored and co-released with ACh at motor nerve terminals and is
      reported to enhance spontaneous synaptic currents by the activation of PKC, also
      shows similar developmental changes in the modulation of embryonic ACh channels
      in Xenopus embryonic myocytes.

PMID- 7512252
TI  - Poster presentations: a tool for evaluating nursing students.
AB  - Developing effective means to evaluate students taking undergraduate nursing
      research and stimulating interest in a course that is typically viewed by nursing
      majors as "irrelevant" is challenging and problematic. Traditional examinations
      and proposal assignments do not inspire undergraduate nursing students to
      appreciate research. The author outlines the steps taken to design and use poster
      presentations to evaluate students' progress and offers recommendations for
      adapting this innovative evaluation tool to clinical content [corrected].

PMID- 7512253
TI  - Maps: understanding theory through the use of analogy.
AB  - When introducing the concepts associated with theory, nurse educators may
      encounter some anxiety on the part of students. Most people, however, have a
      lifetime of familiarity with the practical use of, and ideas about, maps. The
      author reviews what is commonly known about maps to promote a more practical
      grasp of the concepts of scientific theory.

PMID- 7512255
TI  - Lid imbrication syndrome. Diagnosis with rose bengal staining.
AB  - BACKGROUND: Lid imbrication syndrome is an abnormality of lid apposition in which
      the upper lid overlies the lower lid. Patients often complain of irritation,
      tearing, and foreign body sensation. The condition may be difficult to diagnose.
      METHOD: Twenty-one patients with suspected lid imbrication syndrome were compared
      with 21 age-matched controls. All patients were given 0.5% topical rose bengal.
      RESULTS: The diagnosis of lid imbrication syndrome was confirmed by the presence
      of rose bengal staining of the tarsal conjunctiva of the upper lid margin. The
      amount of rose bengal staining correlated with the severity of lid imbrication.
      Eighteen of 21 patients had received a diagnosis previously of dry eye syndrome.
      Four patients had persistent epithelial defects. CONCLUSIONS: Rose bengal
      staining of the superior lid margin tarsal conjunctiva offers an extremely
      reliable aid for diagnosing lid imbrication syndrome. The condition commonly
      presents as a dry eye or persistent epithelial defect. Treatment ranges from
      viscous tear substitutes to horizontal lid shortening of the upper lid.

PMID- 7512254
TI  - Mooren-type hepatitis C virus-associated corneal ulceration.
AB  - BACKGROUND: Two patients with bilateral Mooren-type ulcers had underlying chronic
      hepatitis C virus (HCV) infection. Both patients also had chronic, pruritic
      dermatitis, which in one patient was diagnosed as hidradenitis suppurativa.
      METHODS: Serum from the first patient and serum, conjunctiva, and liver from the
      second patient were analyzed for HCV genomic RNA using the reverse transcriptase
      polymerase chain reaction. Serum anti-HCV antibodies were monitored with a
      commercially available second-generation test. Liver and conjunctival biopsies
      were evaluated histopathologically. RESULTS: Liver biopsy showed severe hepatitis
      in the first patient, but normal liver tissue in the second. Hepatitis C virus
      genomic RNA was detected in the serum of both patients. In the first patient, the
      virus was detected 4 months after completion of interferon alfa-2b treatment for
      chronic active hepatitis. In the second patient, HCV genomic RNA was detected in
      serum, but not in conjunctiva or liver tissue. Hepatitis C virus could not be
      detected in the serum of the second patient after 2 weeks of interferon alfa-2b
      treatment. Both patients had serum anti-HCV antibodies. In case 1, there was a
      marked improvement in the corneal disease during and after 6 months of interferon
      alfa-2b treatment for chronic active hepatitis that paralleled a return of serum
      liver enzyme levels to the normal range. In the second patient, the corneal
      disease improved after 6 weeks of interferon alfa-2b treatment, but abruptly
      worsened when the patient discontinued therapy. The corneal disease improved
      again after interferon alfa-2b was reinstituted. CONCLUSIONS: Chronic HCV virus
      infection is associated with Mooren-type peripheral ulcerative keratitis. All
      patients with Mooren-type ulcers should be tested for evidence of HCV infection
      in consultation with a liver specialist. Even when improvement is obtained with
      interferon alfa-2b treatment, however, continued follow-up is important because
      relapse is common and repeat treatment may be effective.

PMID- 7512256
TI  - Overlays for classroom and optometric use.
AB  - Perceptual distortion of printed text can sometimes be reduced by placing upon
      the page a sheet of coloured plastic (overlay). The colour that best reduces the
      distortion differs from one individual to another and may need to be selected
      with precision. A set of overlays has been developed that samples the CIE UCS
      diagram systematically. The overlays are robust and have a matte finish. They can
      be combined in an intuitive way to provide a wide range of chromaticities.

PMID- 7512257
TI  - Recent approaches to the chemotaxonomy of the Actinobacillus-Haemophilus
      Pasteurella group (family Pasteurellaceae).
AB  - Many members of the Actinobacillus-Haemophilus-Pasteurella group (family
      Pasteurellaceae) have been misclassified. This article reviews the chemotaxonomic
      characters that recently have been provided to improve the taxonomy of
      Pasteurellaceae. These include fatty acids of whole cells, of lipopolysaccharides
      and of single colonies, together with sugar contents of whole cells, of whole
      defatted cells, of lipopolysaccharides and of single colonies. This article also
      reviews taxonomy aided by distribution of proteins in whole cells and outer
      membranes, distribution of enzymes in outer membrane vesicles and in whole cells,
      bacteriolysis induced by ethylenediaminetetraacetic acid and hen eggwhite
      lysozyme and the distribution of respiratory quinones. Furthermore, an overview
      of characters obtained through studies on genetic transformation, restriction
      enzyme analysis, restriction fragment length polymorphism, DNA-DNA hybridization,
      DNA-rRNA hybridization, and 16S rRNA sequencing is given.

PMID- 7512258
TI  - Recombinant human G-CSF (Lenograstim) for infectious complications in glycogen
      storage disease type Ib. Report of 7 cases.
AB  - Seven patients with glycogen storage disease type Ib suffering from severe and/or
      recurrent bacterial infections were treated with glycosylated recombinant G-CSF
      (Lenograstim). Mean follow up was 20.8 months (range 9-30 months). In all cases a
      median dose of 5 micrograms/kg/day resulted in rapid clinical improvement,
      associated in 6/7 with an increase in absolute polymorphonuclear (PMN) count. In
      the remaining subject, a striking amelioration of infectious status contrasted
      with a persistently low PMN count. Liver transplantation in one patient resolved
      metabolic complications but did not improve PMN count or the infectious status,
      while neutropenia was corrected by G-CSF. Prevention of recurrent infections was
      achieved in all cases with intermittent therapy. Short term treatment was well
      tolerated, thrombocytopenia in two patients (WHO grade 0 and grade 3) recovering
      after decrease of G-CSF dosage.

PMID- 7512260
TI  - The hnRNP F protein: unique primary structure, nucleic acid-binding properties,
      and subcellular localization.
AB  - More than 20 different heterogeneous nuclear ribonucleoproteins (hnRNPs) are
      associated with pre-mRNAs in the nucleus of mammalian cells and these proteins
      appear to influence pre-mRNA processing and other aspects of mRNA metabolism and
      transport. The arrangement of hnRNP proteins on pre-mRNAs is likely to be unique
      for each RNA and may be determined by the different RNA-binding preferences of
      each of these proteins. hnRNP F (M(r) = 53 kD, pI = 6.1) and hnRNP H (M(r) = 56
      kD, pI = 6.7-7.1) are abundant components of immunopurified hnRNP complexes and
      they have distinct nucleic acid binding properties. Unlike other hnRNP proteins
      which display a varying range of affinities for different
      ribonucleotidehomopolymers and ssDNA, hnRNP F and hnRNP H bind only to poly(rG)
      in vitro. hnRNP F and hnRNP H were purified from HeLa cells by poly(rG) affinity
      chromatography and oligonucleotides derived from peptide sequences were used to
      isolate a cDNA encoding hnRNP F. The predicted amino acid sequence of hnRNP F
      revealed a novel protein with three repeated domains related to the RNP consensus
      sequence RNA-binding domain. Monoclonal antibodies produced against bacterially
      expressed hnRNP F were specific for both hnRNP F and hnRNP H and recognized
      related proteins in divergent organisms, including in the yeast Saccharomyces
      cerevisiae. hnRNP F and hnRNP H are thus highly related immunologically and they
      share identical peptides. Interestingly, immunofluorescence microscopy revealed
      that hnRNP F and hnRNP H are concentrated in discrete regions of the nucleoplasm,
      in contrast to the general nucleoplasmic distribution of previously characterized
      hnRNP proteins. The unique RNA-binding properties, amino acid sequence and
      distinct intranuclear localization of hnRNP F and hnRNP H make them novel hnRNP
      proteins that are likely to be important for the processing of RNAs containing
      guanosine-rich sequences.

PMID- 7512259
TI  - A group III twintron encoding a maturase-like gene excises through lariat
      intermediates.
AB  - The 1605 bp intron 4 of the Euglena gracilis chloroplast psbC gene was
      characterized as a group III twintron composed of an internal 1503 nt group III
      intron with an open reading frame of 1374 nt (ycf13, 458 amino acids), and an
      external group III intron of 102 nt. Twintron excision proceeds by a sequential
      splicing pathway. The splicing of the internal and external group III introns
      occurs via lariat intermediates. Branch sites were mapped by primer extension RNA
      sequencing. The unpaired adenosines in domains VI of the internal and external
      introns are covalently linked to the 5' nucleotide of the intron via 2'-5'
      phosphodiester bonds. This bond is susceptible to hydrolysis by the debranching
      activity of the HeLa nuclear S100 fraction. The internal intron and presumptive
      ycf13 mRNA accumulates primarily as a linear RNA, although a lariat precursor can
      also be detected. The ycf13 gene encodes a maturase-like protein that may be
      involved in group III intron metabolism.

PMID- 7512261
TI  - Transactivation and repression of the alpha-fetoprotein gene promoter by retinoid
      X receptor and chicken ovalbumin upstream promoter transcription factor.
AB  - Retinoic acid (RA) is widely involved in the control of cell proliferation and
      differentiation, as well as embryo pattern formation. Transcription of the
      oncodevelopmental protein, alpha-fetoprotein (AFP), is stimulated by retinoic
      acid (RA) in neoplastic cells. To study RA regulation of AFP gene expression, the
      5'-flanking region of AFP gene was cloned and analyzed. In the present study,
      transfection of deletion mutants and sequence analysis revealed a retinoid X
      receptor response element (AFP-RXRE) located at position -139 to -127 of the AFP
      promoter. Synthetic AFP-RXRE was ligated into a reporter construct with the
      heterologous promoter and chloramphenicol acetyltransferase (CAT). AFP-RXRE
      conferred a marked RA responsiveness in the cotransfection with retinoid X
      receptor (RXR), but not with retinoic acid receptors (RARs). Consistent with
      these data, only RXR bound to AFP-RXRE with high affinity in the mobility shift
      assays. Chicken ovalbumin upstream promoter transcription factor (COUP-TF), an
      orphan member of the steroid/thyroid hormone superfamily, also demonstrated
      specific binding activity to AFP-RXRE in vitro. In cotransfection assays, COUP-TF
      dramatically repressed the transactivation of RXR on AFP-RXRE. The mechanism of
      repression by COUP-TF may involve the mutual occupancy of the AFP-RXRE binding
      site between RXR and COUP-TF.

PMID- 7512264
TI  - Identification of the cephalosporin human serum albumin binding sites.
AB  - We have demonstrated that the cephalosporins which possess heterozyclic
      pentagonal group substituents bind to the bilirubin binding site on albumin,
      while the cephalosporins which possess hexagonal hydrocarbon cycle substituents
      bind to the benzodizepine binding sites (site II) on albumin. No binding of
      cephalosporins to the so-called site I and fatty acids binding site on human
      albumin was demonstrated.

PMID- 7512263
TI  - Release of 5'-terminal deoxyribose-phosphate residues from incised abasic sites
      in DNA by the Escherichia coli RecJ protein.
AB  - Excision of deoxyribose-phosphate residues from enzymatically incised abasic
      sites in double-stranded DNA is required prior to gap-filling and ligation during
      DNA base excision-repair, and a candidate deoxyribophosphodiesterase (dRpase)
      activity has been identified in E. coli. This activity is shown here to be a
      function of the E. coli RecJ protein, previously described as a 5'-->3' single
      strand specific DNA exonuclease involved in a recombination pathway and in
      mismatch repair. Highly purified preparations of dRpase contained 5'-->3'
      exonuclease activity for single-stranded DNA, and homogeneous RecJ protein
      purified from an overproducer strain had both 5'-->3' exonuclease and dRpase
      activity. Moreover, E. coli recJ strains were deficient in dRpase activity. The
      hydrolytic dRpase function of the RecJ protein requires Mg2+; in contrast, the
      activity of E. coli Fpg protein, that promotes the liberation of 5'-->3'Rp
      residues from DNA by beta-elimination, is suppressed by Mg2+. Several other E.
      coli nucleases, including exonucleases I, III, V, and VII, endonucleases I, III
      and IV and the 5'-->3' exonuclease function of DNA polymerase I, are unable to
      act as a dRpase. Nevertheless, E. coli fpg recJ double mutants retain capacity to
      repair abasic sites in DNA, indicating the presence of a back-up excision
      function.

PMID- 7512266
TI  - [Detection of the intermediate trophoblast as evidence of intrauterine
      pregnancy].
AB  - With spontaneous abortion the conceptus is often expelled and lost right at the
      beginning, and uterine curettings then contain only endometrial fragments and
      clotted blood. Even complete embedding of all available material for histologic
      examination will not reveal any chorionic villi, and ectopic pregnancy can thus
      not be excluded. In such cases, the intermediate trophoblast can sometimes still
      be demonstrated within the endometrial tissue. This highly invasive trophoblast
      is difficult to identify using conventional staining, but cytokeratin antibodies
      are reliable markers of this cell type. Using immunohistochemistry, these fetal
      components could be demonstrated in 27 of 95 specimens (28.5%), proving the
      intrauterine nature of the aborted pregnancy. In some cases the fetal derivation
      of intermediate trophoblast was demonstrated by using in situ hybridisation to
      mark repetitive sequences on the Y-chromosome in the interphase nucleus.

PMID- 7512262
TI  - Alu transcripts: cytoplasmic localisation and regulation by DNA methylation.
AB  - Full length Alu transcripts in HeLa cells are detected by primer extension using
      reverse transcriptase and are also analyzed as cloned cDNA sequences. The 5' end
      of these transcripts corresponds to the transcriptional start site for RNA
      polymerase III indicating that these RNAs are transcribed from their internal
      polymerase III promoters. The Alu transcripts found in cytoplasmic poly A+ RNAs
      appear to be organized into RNPs as assayed by sucrose gradient sedimentation.
      Present at about one hundred to one thousand copies per cell, the Alu transcripts
      are rare as compared to 7SL RNA. In agreement with previous reports that
      methylation inhibits Pol III-directed transcription of Alu in vitro, treatment of
      HeLa cells with 5-azacytidine results in Alu DNA hypomethylation and an increase
      in the abundance of the Alu transcript. Sequence analysis shows that many
      different Alu repeats including members of all subfamilies are transcribed by Pol
      III in vivo. cDNA sequences of the Pol III-directed transcripts exactly match the
      A box of the Pol III promoter element whereas in other Alu transcripts this
      element is not faithfully conserved.

PMID- 7512265
TI  - Changes in expression of the albumin, fibronectin and type I procollagen genes in
      CCl4-induced liver fibrosis: effect of pyridoxol L,2-pyrrolidon-5 carboxylate.
AB  - The protective activity of pyridoxol L,2-pyrrolidon-5 carboxylate (metadoxine)
      was investigated in a rat model of carbon tetrachloride (CCL4)-induced hepatic
      fibrosis. After 6 weeks of CCl4 treatment, the animals developed fibrosis and
      inflammation of the liver while those treated with CCl4 + metadoxine had less
      severe lesions (P < 0.05). Since in liver fibroplasia there are quantitative
      changes of the extracellular matrix components and almost invariably a decrease
      in albumin synthesis, we have also investigated by Northern blot analysis the
      expression of the cellular fibronectin, pro-alpha 2(I)collagen and albumin genes.
      There were striking increases in fibronectin and pro-alpha 2(I)collagen mRNA
      contents in the livers of CCL4-treated animals and these enhancements were less
      evident in the metadoxine-treated rats. In contrast, albumin mRNA levels, almost
      identical in control and metadoxine-treated rats, were lower in the CCl4-treated
      animals. These data suggest that metadoxine might slow the development of CCl4
      mediated liver fibrosis.

PMID- 7512267
TI  - The relationship of uterine and umbilical Doppler resistance to fetal and
      placental protein synthesis in the second trimester.
AB  - The relation of uteroplacental and umbilical Doppler resistance index (RI) to
      peripheral levels of alphafetoprotein (AFP), human chorionic gonadotrophin (hCG),
      human placental lactogen (HPL), Schwangerswaft protein (SP1), pregnancy
      associated placental protein A (PAPP-A) and insulin-like growth factor binding
      protein 1 (IGP-BP1) at 16-24 weeks was established in a cross-sectional study of
      183 unselected singleton pregnancies. There was an association between high
      values of uteroplacental RI and high hCG levels, and high umbilical RI values
      with high hCG and HPL levels. Thus, in the mid-trimester, the levels of some
      placental proteins seem to be related to placental resistance.

PMID- 7512268
TI  - Model properties underlying non-identifiability in single channel inference.
AB  - Models of ion channel kinetics subserve inferential methods applied to patch
      clamp data. For Markov models the density function of a sojourn time in a class
      of states is a mixture of exponentials. Determination of kinetic parameters from
      density functions may be complicated by non-uniqueness of solutions. This non
      identifiability is investigated analytically for a class of two states, assuming
      detailed balance; relations between model properties, observable density
      parameters, and non-uniqueness are presented. The results are further developed
      in terms of similarity transform methods. Additional information provided by
      joint distributions is discussed. An example is given where identifiability of a
      model can be demonstrated explicitly. Attention is drawn to instances where the
      number of components in a density function may be misleading when used to infer
      the number of underlying states.

PMID- 7512269
TI  - The effect of polyols on the stability of duplex DNA.
AB  - It has been observed that double stranded DNA in solution is thermally
      destabilized by the presence of several organic molecules, among which are
      alcohols and polyols. This finding, and the fact that sugar moieties are
      components of some nuclear proteins and DNA binding drugs, may suggest a role for
      oligosaccharides in DNA recognition and/or interaction. In order to investigate
      this possibility, the effect of several sugars and other polyols on the thermal
      stability and on the conformation of DNA has been studied by high sensitivity
      differential scanning calorimetry and circular dichroism. While addition of small
      size polyols does not influence appreciably the melting enthalpy, it always
      results in a decrease in the DNA melting temperature. The magnitude of the
      destabilizing effect depends on the concentration of additives, reaching 13.5
      degrees C in 50% (5.4M) glycerol. It also depends on the nature of the additives,
      e.g., sorbitol is more efficient than inositol, while dextran has no effect on
      the DNA melting temperature. According to circular dichroism results, DNA
      undergoes a significant structural change in the presence of small sugars or
      polyols: a continuous loss in 'B' character is observed as the glycerol
      concentration is gradually increased. This conformation change appears to be
      related to the decrease in thermostability.

PMID- 7512270
TI  - Freud's bestiary: how does psychoanalysis treat animals?

PMID- 7512271
TI  - Clinical evaluation of serum alpha-fetoprotein (AFP) and protein induced by
      vitamin K absence or antagonist-II (PIVKA-II) levels in patients with
      hepatocellular carcinoma following interventional radiology.
AB  - Fourteen patients with unrespectable HCC were treated with various interventional
      radiology (IVR) procedures. The initial therapeutic response was determined using
      computed tomography (CT) findings, and determinations of serum alpha-fetoprotein
      (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II)
      levels. When CT studies of the initial response to IVR were compared with changes
      in the serum AFP and PIVKA-II levels, the AFP level was found to correlate more
      closely than the PIVKA-II levels. The PIVKA-II level correlated more closely than
      the AFP level in cases with poor response to IVR. Both of these tumor markers
      should be measured in combination with the diagnostic imagings for follow-up
      studies of IVR.

PMID- 7512272
TI  - Gene expression of potential morphogens during hair follicle and tooth formation:
      a review.
AB  - Early work on the morphogenesis of hairs and teeth was largely descriptive
      histology and established the times and order of visible initiation of anlagen
      and their patterns of development. However, in the last 30 years, many growth
      factors have been discovered; more recently, their expression during
      morphogenesis has been determined and immunohistochemistry has enabled the
      visualization of structural elements of organs. This review is concerned
      primarily with aspects of these recent phases of research with respect to the
      formation of hairs and, to a lesser degree, teeth. The expression of several
      growth factors including bone morphogenetic proteins 2 and 4, the glycoprotein
      tenascin, the proteoglycan syndecan, and the expression of the mammalian
      homologue of Notch, cadherins and epimorphin is examined here during the early
      stages of organogenesis, primarily to review the type of research that should be
      extended to the organogenesis of wool fibres in Merino sheep. Signal
      transduction, the third and increasingly complex phase of research that is now
      rapidly developing, follows the establishment of ligand-receptor complexes during
      morphogenesis and is included here in a preliminary way.

PMID- 7512273
TI  - Drug-induced lupus.
AB  - Recent years have seen promising developments in both our appreciation of the
      spectrum of autoimmune phenomena associated with DIL as well as our understanding
      of the pathogenesis of this disease. From our present knowledge, it seems likely
      that the cause of DIL is multifactorial, and that the disease manifestations
      depend on both the drugs involved as well as predisposing host factors. The
      present availability of an animal model of DIL promises to further our
      understanding of the role of drugs and other environmental factors in this
      disorder. It is hoped that further studies will provide additional understanding
      of the pathogenesis of these lupus-like diseases and possibly bring us one step
      closer to providing more rational and effective treatments for patients with
      idiopathic lupus.

PMID- 7512274
TI  - [Acute phase reactants. Their clinical usefulness].

PMID- 7512275
TI  - Chemotherapy and granulocyte colony-stimulating factor in ovarian cancer.

PMID- 7512276
TI  - Dose-intensive chemotherapy in extensive-stage small cell lung cancer.

PMID- 7512277
TI  - The role of granulocyte colony-stimulating factor and granulocyte-macrophage
      colony-stimulating factor in chemotherapy for lung cancer.

PMID- 7512278
TI  - The application of hematopoietic growth factors in advanced transitional cell
      carcinoma of the urinary tract.

PMID- 7512279
TI  - The role of granulocyte colony-stimulating factor with dose-intensive
      chemotherapy.

PMID- 7512280
TI  - Effect of recombinant human granulocyte colony-stimulating factor in patients
      receiving methotrexate/vinblastine/doxorubicin/cisplatin therapy for the
      treatment of transitional cell carcinoma of the urinary tract.

PMID- 7512281
TI  - The medication minute: Finasteride.

PMID- 7512282
TI  - Screening for prostate cancer.

PMID- 7512283
TI  - Hidradenitis in a patient with AIDS: palliation with superficial radiation.

PMID- 7512284
TI  - Charcot arthropathy of the spine with resulting paraparesis developing during
      pregnancy in a patient with congenital insensitivity to pain. A case report.
AB  - This is a report of a 17-year-old female with congenital insensitivity to pain
      who was noted to develop significant truncal asymmetry during pregnancy. A dense
      paraparesis developed 10 days after delivery. Charcot arthropathy of the spine
      had resulted in severe destructive changes of both L3 and L4 with significant
      canal compromise. The patient made a complete neurologic recovery after anterior
      decompression and stabilization of the spine.

PMID- 7512285
TI  - Efficacy of short term versus long term tube thoracostomy drainage before
      tetracycline pleurodesis in the treatment of malignant pleural effusions.
AB  - BACKGROUND: A study was undertaken to compare the efficacy of short term tube
      thoracostomy drainage with standard tube thoracostomy drainage before
      instillation of tetracycline for sclerotherapy of malignant pleural effusions.
      METHODS: The study consisted of a randomised clinical trial in a sequential
      sample of 25 patients with malignant pleural effusions documented
      cytopathologically. Fifteen patients were randomly assigned to group 1 (standard
      protocol) and 10 to group 2 (short term protocol). Patients in group 1 had tube
      thoracostomy suction drainage until radiological evidence of lung re-expansion
      was obtained and the amount of fluid drained was < 150 ml/day, before
      tetracycline (1.5 g) was instilled. The chest tube was removed when the amount of
      fluid drained after instillation was < 150 ml/day. Patients in group 2 also had
      suction drainage, but the tetracycline (1.5 g) was instilled when the chest
      radiograph showed the lung to be re-expanded and the effusion drained, which was
      usually within 24 hours. The chest tube was removed the next day. RESULTS: The
      response to tetracycline sclerotherapy in the two groups was the same (80%) but
      the duration of chest tube drainage was significantly shorter for patients in
      group 2 (median two days) than for those in group 1 (median seven days).
      CONCLUSIONS: The duration of chest tube drainage before sclerotherapy for
      malignant pleural effusions need not be influenced by the amount of fluid drained
      daily but by radiographic evidence of fluid evacuation and lung re-expansion.
      Shorter duration of drainage will reduce the length of hospital stay without
      sacrificing the efficacy of pleurodesis.

PMID- 7512286
TI  - Insertion of a self-expandable endotracheal metal stent using topical anaesthesia
      and a fibreoptic bronchoscope: a comfortable way to offer palliation.
AB  - A self-expandable stent was used to obtain prolonged relief of stridor resulting
      from tracheal obstruction by extrinsic tumour compression despite prior external
      irradiation. The stent was inserted in an easy and comfortable procedure with
      fibreoptic bronchoscopy under local anaesthesia.

PMID- 7512287
TI  - Cutaneous reactions to thiacetazone in Zambia--implications for tuberculosis
      treatment strategies.
AB  - Tuberculosis in patients infected with human immunodeficiency virus (HIV) is a
      growing threat to public health in Africa. Thiacetazone, one of the continent's
      most widely used antituberculous agents, may lead to severe cutaneous reactions
      in the HIV infected individual. We describe the impact of this reaction on the
      tuberculosis (TB) control programme of a district hospital in Zambia in 1990, and
      examine the cost implications of changing the standard treatment regime. We
      carried out a retrospective survey of records of all patients beginning TB
      treatment in 1990, together with HIV test results and the cost of all treatments
      given. From this we derived estimates of costs of different regimes which are and
      could be used in TB control in Zambia. Severe reactions occurred in 18.7% of all
      HIV seropositive patients receiving thiacetazone, fatally so in 1.2% (odds ratio
      16.6). The greatest part of the cost of the current regime is that attributable
      to the inpatient stay; we estimated that 29.4% of patients would be unable to
      receive drugs as out-patients but, even allowing for this, rifampicin-based
      regimes given to outpatients where possible would not cost more than the current
      strategy. We conclude that ethical and economic considerations support a change
      to rifampicin-based regimes in areas of Africa where HIV seroprevalence is high.

PMID- 7512288
TI  - CD59 (protectin) molecule, resistance to complement, and virulence of Entamoeba
      histolytica.

PMID- 7512290
TI  - A PEG-ELISA for the detection of Leishmania donovani antigen in circulating
      immune complexes.
AB  - Leishmanial antigen in circulating immune complexes (CIC) from sera of cotton
      rats experimentally infected with Leishmania donovani and visceral leishmaniasis
      patients (VLP) was detected using a polyethylene glycol (PEG) enzyme-linked
      immunosorbent assay (PEG-ELISA). The immune complexes were precipitated in the
      cold with 12% PEG (average M(r) 6000) and then dissociated with glycine-HCl
      buffer. The dissociated antigen bound to the plate was then detected by
      peroxidase-labelled rabbit antibody raised to either amastigotes or to CIC. Serum
      samples from either controls or patients infected with heterologous organisms
      were used to define the sensitivity and specificity of the test. Leishmanial
      antigen was detected in the CIC from all experimentally infected animals (100%
      sensitivity) and in 22 of 25 of the CIC from VLP (88% sensitivity), using either
      conjugate. Immunoblotting of PEG-precipitated CIC from infected animals with both
      rabbit antisera revealed multiple antigen components. Antigens of 40, 42 and 45
      kDa appeared to be specifically recognized by both antibodies; the components of
      40 and 42 kDa were common to amastigote extracts and CIC from infected animals.

PMID- 7512289
TI  - Fluorescence microscopy using a light microscope fitted with an interference
      filter for the diagnosis of malaria.

PMID- 7512291
TI  - Small intestinal transplantation in humans with or without the colon.
AB  - Under FK506-based immunosuppression, 16 cadaveric small bowel transplantations
      were performed in 15 recipients with (n = 5) or without (n = 11) the large bowel.
      Twelve (80%) patients are alive after 1.5 to 19 months, 11 bearing their grafts,
      of which 4 include colon. The actuarial one-year patient and graft survivals are
      87.5% and 65.9%, respectively. Five grafts were lost to acute (n = 4) or chronic
      (n = 1) rejection, and 3 of these patients subsequently died after 376, 440, and
      776 days total survival. Six recipients developed severe CMV infection that was
      strongly associated with seronegative status preoperatively and receipt of grafts
      from CMV positive donors; 3 died, and the other 3 required prolonged
      hospitalization. Currently, 9 patients are free from TPN 1-18 months
      postoperatively, 2 require partial TPN, and one has returned to TPN after graft
      removal. The results show the feasibility of small bowel transplantation but
      emphasize the difficulty of managing these recipients not only early but long
      after their operation.

PMID- 7512293
TI  - FK506 "rescue" for resistant rejection of renal allografts under primary
      cyclosporine immunosuppression.
AB  - Seventy-seven patients with ongoing acute rejection on initial CsA therapy were
      converted to FK506 to attempt graft salvage. Fifty-nine patients had undergone
      primary transplantation and 18 had been retransplanted; there were 52 cadaveric
      and 25 living-donor transplants. The indications for conversion to FK506 were
      ongoing, biopsy-confirmed rejection in all patients, including vascular rejection
      in 20. The median interval to rescue was 2 months (range 2 weeks to 36 months)
      after transplantation. Sixty-one of the 77 patients (79%) had already received
      one or more courses of an antilymphocyte preparation (OKT3: n = 33; ALG or ATG: n
      = 1; OKT3+ALG/ATG: n = 27). Of the 77 patients, 57 (74%) have been successfully
      rescued and still have functioning grafts with a mean follow-up of 14 months,
      with a mean serum creatinine of 2.35 +/- 0.97 mg/dl. Eighteen patients were
      already dialysis-dependent at the time of conversion to FK506; of these, 9 (50%)
      were successfully salvaged and have a mean serum creatinine of 2.3 mg/dl. Of the
      61 patients previously treated with antilymphocyte preparations, 48 (79%) were
      rescued. In those salvaged, prednisone doses have been lowered from 22.2 +/- 7.2
      mg/day preconversion to 7.5 +/- 5.6 mg/day postconversion, and 12 patients are on
      FK506 monotherapy. In nondiabetics, mean serum glucose was 101.4 +/- 20.5 mg/dl
      preconversion and 93.2 +/- 22 postconversion (P = 0.07), uric acid 7.3 +/- 2.3
      and 7.1 +/- 1.5 mg/dl (P = 0.53), and triglycerides 199.2 +/- 101.6 and 167.2 +/-
      106.4 mg/dl (P = 0.06). Cholesterol levels were significantly lower following FK
      conversion (207.7 +/- 46.5 mg/dl pre. vs. 188.3 +/- 39.7 post., P = 0.007). FK506
      is capable of salvaging renal allografts with ongoing acute rejection on CsA
      therapy, even when antilymphocyte preparations have been ineffective.

PMID- 7512292
TI  - A prospective randomized trial of FK506 versus cyclosporine after human pulmonary
      transplantation.
AB  - We have conducted a unique prospective randomized study to compare the effect of
      FK506 and cyclosporine (CsA) as the principal immunosuppressive agents after
      pulmonary transplantation. Between October 1991 and March 1993, 74 lung
      transplants (35 single lung transplants [SLT], 39 bilateral lung transplant
      [BLT]) were performed on 74 recipients who were randomly assigned to receive
      either FK or CsA. Thirty-eight recipients (19 SLT, 19 BLT) received FK and 36
      recipients (16 SLT, 20 BLT) received CsA. Recipients receiving FK or CsA were
      similar in age, gender, preoperative New York Heart Association functional class,
      and underlying disease. Acute rejection (ACR) was assessed by clinical,
      radiographic, and histologic criteria. ACR was treated with methylprednisolone, 1
      g i.v./day, for three days or rabbit antithymocyte globulin if steroid-resistant.
      During the first 30 days after transplant, one patient in the FK group died of
      cerebral edema, while two recipients treated with CsA died of bacterial pneumonia
      (1) and cardiac arrest (1) (P = NS). Although one-year survival was similar
      between the groups, the number of recipients free from ACR in the FK group was
      significantly higher as compared with the CsA group (P < 0.05). Bacterial and
      viral pneumonias were the major causes of late graft failure in both groups. The
      mean number of episodes of ACR/100 patient days was significantly fewer in the FK
      group (1.2) as compared with the CsA group (2.0) (P < 0.05). While only one
      recipient (1/36 = 3%) in the group treated with CsA remained free from ACR within
      120 days of transplantation, 13% (5/38) of the group treated with FK remained
      free from ACR during this interval (P < 0.05). The prevalence of bacterial
      infection in the CsA group was 1.5 episodes/100 patient days and 0.6 episodes/100
      patient days in the FK group. The prevalence of cytomegaloviral and fungal
      infection was similar in both groups. Although the presence of bacterial, fungal,
      and viral infections was similar in the two groups, ACR occurred less frequently
      in the FK-treated group as compared with the CsA-treated group in the early
      postoperative period (< 90 days). Early graft survival at 30 days was similar in
      the two groups, but intermediate graft survival at 6 months was better in the FK
      group as compared with the CsA group.

PMID- 7512295
TI  - Alpha 1-antichymotrypsin production in PSA-producing cells is common in prostate
      cancer but rare in benign prostatic hyperplasia.
AB  - OBJECTIVE: To investigate the distribution and production of alpha 1
      antichymotrypsin (ACT) and prostate-specific antigen (PSA) in benign hyperplastic
      and malignant prostatic tissue, respectively. METHODS: Using monoclonal anti-ACT
      and anti-PSA IgGs for immunocytochemistry and alkaline phosphatase conjugated 30
      mer oligodeoxynucleotide probes for nonradioactive in situ hybridization, tissue
      specimens were studied from 15 patients with benign prostatic hyperplasia after
      transurethral resection of the prostate (TURP) and from 9 patients with bladder
      cancer who underwent cystoprostatectomy. Cancer specimens were from 23 TURP
      patients and from ultrasound guided core biopsies in 14 patients. Prostate tumors
      were graded according to the Gleason system. RESULTS: We found no or only
      occasional small foci of immunostaining for ACT, and no ACT transcripts in the
      PSA-producing epithelium in areas with benign nodular hyperplasia. By contrast, a
      high proportion of cells expressed both ACT and PSA in prostate cancers with low
      Gleason score, as detected by immunocytochemistry and in situ hybridization.
      Poorly differentiated tumor cells manifested greater variation in immunostaining
      for both ACT and PSA. As compared to tumors of low Gleason score, high-score
      tumors less frequently manifested immunostaining for ACT than for PSA, and less
      frequently generated hybridization signals for both PSA and ACT transcripts.
      CONCLUSIONS: A significantly higher proportion of serum PSA has been reported to
      be complexed to ACT in patients with prostate cancer than in patients with benign
      prostatic hyperplasia. The presently reported lack of ACT production in PSA
      containing BPH nodules may contribute to this by making conditions less optimal
      for complex formation between PSA and ACT. As opposed to this, production of both
      ACT and PSA in prostate cancers may enhance the complex formation between PSA and
      ACT.

PMID- 7512294
TI  - The correlation between donor characteristics and the success of human islet
      isolation.
AB  - Clinical islet allotransplantation is dependent on the ability to achieve a high
      yield and purity of islets isolated from human cadaver pancreas donors. The aim
      of this study was to determine the factors influencing the pancreas prior to
      islet isolation that may alter yield and purity. The results of 50 consecutive
      islet isolations from cadaver donor human pancreati at the University of Chicago
      Medical Center from December 1991 to April 1993 were analyzed. All pancreati were
      first offered for whole pancreas transplantation before being considered for
      islet isolation. Human pancreatic islet isolation was accomplished by a modified
      automated method. Some islet isolations resulted in a high islet yield but low
      islet purity. Other resulted in well-purified islets, but a low yield.
      Arbitrarily, successful islet isolation is defined as that yielding over 250,000
      islet equivalents (EQN) with a purity of at least 80%. The success rate of human
      pancreatic islet isolation was 70%. The mean final islet yield obtained from
      these 50 pancreati was 300,000 +/- 131,000 islet EQN. The mean purity of the
      final preparation was 73% +/- 25%. By univariate analysis, five factors were
      found to affect significantly the yield, purity, or overall success rate of islet
      isolation: organ cold ischemic time, donor age, donor plasma glucose levels,
      donor body weight, and cause of donor death. Even when islet isolation was
      successful, the function of islets from hyperglycemic and older donors appear to
      be impaired both in vitro and in vivo. These results suggest that islet yield and
      purity are affected by multiple donor-related factors. Even when adequate yield
      and purity are obtained, islet function is also dependent on donor variables.

PMID- 7512296
TI  - Use of terazosin in prostatodynia and validation of a symptom score
      questionnaire.
AB  - OBJECTIVE: The purpose of this trial was to study the use of terazosin in
      nonbacterial prostatitis/prostatodynia, and to evaluate a new symptom score sheet
      for this disease. METHODS: Twenty-five patients who presented with lower urinary
      tract symptoms suggestive of prostatitis were evaluated for evidence of bacterial
      infection by Meares-Stamey criteria and found to be negative. They were then
      treated with the alpha-blocking drug terazosin in doses from 1 to 10 mg. A
      symptom score index for prostatitis was developed, tested in these patients, and
      validated against patients with benign prostatic hyperplasia. Normal control
      patients, who presented for vasectomy, were studied as well. RESULTS: Nineteen
      patients (76%) responded to one month's therapy, with 11 (58%) remaining
      asymptomatic three months later. The symptom score index, as measured by
      Cronbach's alpha measure of index reliability, was excellent at 0.78 and logistic
      regression analysis demonstrated each prostatitis question to have independent
      validity (P < 0.001) but not to the extent of the combined score. CONCLUSIONS:
      Terazosin appears effective in treating patients with nonbacterial
      prostatitis/prostatodynia. This new symptom score is one way to evaluate and
      track patients with this disease. A randomized, placebo-controlled clinical trial
      has been initiated to study this.

PMID- 7512297
TI  - Extensive neodymium-YAG photoirradiation of the prostate in men with obstructive
      prostatism.
AB  - OBJECTIVE: To determine if high-dosage, extensive photoirradiation of the
      prostate could be used safely in men with large prostate glands and obstruction,
      coupled with acceptable clinical results. METHODS: Treatment of 25 men
      consecutively with eight quadrant photoirradiation of the prostate. Treatment of
      the next 25 men with high-dosage energy up to 109,000 joules. Simultaneous
      transrectal needle biopsy of the prostate performed on all 50 men after
      treatment. Patients evaluated with four- to sixteen-month follow-up. RESULTS:
      Success rate of 86 percent on all patients with mean American Urological
      Association (AUA) symptom score decreasing by nineteen points and mean peak
      uroflow rate increasing by 7.9 cc. Needle biopsy after high-dosage laser therapy
      shows no laser effect on the peripheral zone. CONCLUSIONS: High-dosage laser
      energy can be used safely, and allows us to treat large prostates with excellent
      clinical results and minimal complications.

PMID- 7512299
TI  - Optimization of transurethral hyperthermia: number of treatments.
AB  - OBJECTIVE: The optimal number of transurethral microwave hyperthermia (TUHT)
      treatments in patients with moderate to severe symptoms of benign prostatic
      hyperplasia (BPH) is not known. This study was designed to compare TUHT efficacy
      with the use of three versus six treatments. METHODS: In a Phase II prospective
      trial during a three-month period, 28 poor surgical risk patients with moderate
      to severe prostatism were randomized to receive three or six TUHT sessions. TUHT
      treatments were given on an outpatient basis without sedation or anesthesia for
      sixty minutes at 915 MHz with the temperature controlled on the urethral surface
      at 45 degrees C. RESULTS: Subjective improvement was obtained in 7 (50%) patients
      receiving three TUHT treatments and in 12 (86%) patients receiving six
      treatments. A greater degree of improvement in total symptom score (P = 0.01) and
      obstructive (P = 0.01) and irritative (P = 0.04) symptoms was also recorded in
      the 14 patients receiving six treatments compared to those treated with three
      TUHT sessions (P = 0.01). A posttreatment improvement in objective study
      parameters was recorded for both treatment groups. The 14 patients treated with
      six TUHT sessions, however, showed a better improvement in peak flow rates (51%
      vs. 8.4%, P = 0.003) and postvoiding residual volume compared to the 14 patients
      treated with three TUHT sessions (P = 0.10). Treatments were very well tolerated
      and no clinically significant toxicity was recorded. Of the 9 study patients who
      failed to respond to treatment, 1 patient was successfully retreated with TURP
      while 8 patients required an indwelling catheter. CONCLUSIONS: In TUHT in poor
      surgical risk patients with BPH with the temperature controlled at 45 degrees C,
      six treatments were superior to three treatments, based on a higher incidence of
      subjective and objective improvement.

PMID- 7512298
TI  - Predicted and actual change in serum PSA following prostatectomy for BPH.
AB  - OBJECTIVE: To determine the relationship between prostatic adenoma volume and
      serum prostate-specific antigen (PSA) levels in patients with benign prostatic
      hyperplasia (BPH), and to compare the predicted change in serum PSA following
      prostatectomy with the actual change observed. METHODS: Transrectal ultrasound
      (TRUS) estimation of prostatic adenoma (transition zone) and total gland volumes
      were calculated in 96 patients prior to prostatectomy. BPH was confirmed
      histologically following transurethral prostatectomy (in 86) and open
      prostatectomy (in 10). Serum PSA was measured preoperatively in all patients and
      post-operatively in 87 patients. RESULTS: Correlation coefficients of 0.607 and
      0.614 were observed between PSA and adenoma and total gland volumes,
      respectively. The geometric mean ratio of PSA to adenoma volume was 0.120
      micrograms/L/cc with 95% CI (0.104, 0.139) and to total gland volume was 0.068
      micrograms/L/cc with 95% CI (0.058, 0.078). TRUS-determined adenoma and total
      gland volumes correlated well (r = 0.915), as did TRUS-determined adenoma volume
      and resected weight (r = 0.878). The mean ratio of change in PSA to resected
      weight was -0.096 micrograms/L/g with 95% CI (-0.128, -0.064). Neither total
      gland volume nor operation type affected the relationship between change in serum
      PSA and resected weight. CONCLUSIONS: The adenoma should be the main determinant
      of serum PSA levels in patients with BPH. TRUS adenoma volume measurement is
      therefore the most appropriate preoperative measure when one is interpreting
      elevated levels of serum PSA in men thought clinically to have BPH.

PMID- 7512300
TI  - Effects of cystoscopy on PSA levels.

PMID- 7512301
TI  - [Economic public health aspects of benign prostatic hyperplasia in Austria].
AB  - Benign prostatic hyperplasia (BPH) is one of the most frequent diseases in
      advanced aged men. The introduction of a new coding system (ICD-VESKA) in 1989
      made it possible to analyze the number of hospitalized cases and to calculate the
      costs of inpatient care. In 1990 10,710 BPH cases were treated within Austrian
      hospitals. Controlling for multiple entries 9,742 individual patients (269.4 per
      100,000) were treated 138,761 days. Case fatality was 0.5% (46 deaths). The
      number of inpatients comprises only the top 1,3% of morbidity, the total number
      is estimated with 770,000 patients. Based on the official nursing fees total
      costs in public affiliated hospitals were AS 250 millions. Including private
      hospitals total costs increase to AS 306 millions. The inpatient care of BPH
      represents only a small proportion of the total health and economic burden, which
      obviously mainly occurs in the outpatient system. Therefore BPH is one of the
      diseases of which social and economic importance is usually underestimated due to
      a lack of information.

PMID- 7512302
TI  - Formation of the 3' end of yeast mitochondrial mRNAs occurs by site-specific
      cleavage two bases downstream of a conserved dodecamer sequence.
AB  - Mitochondrial mRNAs in yeast arise by processing of polygenic primary transcripts
      at a conserved dodecamer sequence (5'-AAUAAPyAUUCUU-3'). Previous results
      indicated that processing at dodecamer sites interrupted the sequence implying
      that it functioned primarily as a signal for 3' end formation of mRNAs. We have
      determined the precise cleavage site for RNAs processed at the dodecamer
      sequences associated with the oli1 gene and the omega intron of the 21S rRNA
      gene. In both cases cleavage occurred two bases downstream of the site.
      Hydrolysis left the PO4 group attached to the 3' terminus of the cleavage
      products. These results demonstrate for the first time that mature mitochondrial
      mRNAs terminate with an intact dodecamer sequence. In light of the recent
      identification of a protein complex within mitochondria that binds to RNAs
      terminating with an intact dodecamer sequence, these results support the idea
      that the dodecamer sequence functions not only within pre-mRNAs as a processing
      site, but within mature mRNAs as well, possibly for the stabilization and/or
      translation.

PMID- 7512303
TI  - Innervation of the patella. An immunohistochemical study in mice.
AB  - In the mouse, arthritis was induced by a single sub-patellar intraarticular
      injection of bacterial collagenase. This procedure induces also patellar
      malalignment. A rich innervation of thin varicose calcitonin gene-related peptide
      (CGRP) and substance P (SP) immunoreactive fibers was found in the joint capsule,
      in the periosteum of the patella, in the synovial tissues at the lateral border
      of the patella, in the femoral groove, and in the subchondral bone of the patella
      and femur. Moreover, fibers were found in plica tissues between the quadriceps
      and patellar tendon, and the femoral groove. After the collagenase treatment, the
      general innervation pattern was comparable to that of the controls, but CGRP and
      SP innervation was no longer detectable with the antibodies in the plica tissues,
      and was to a lesser extent detectable in the fat pad of the patella, in the
      lateral borders of the patella and in the proliferated synovial tissues. Signs of
      degenerated axonal profiles were observed in these locations with a polyclonal
      antibody to the growth-associated protein GAP-43/B-50. At all the other
      peripheral locations, such as the muscles, the GAP-43/B-50 distribution was
      normal.

PMID- 7512304
TI  - Regulation of insulin-like growth factor binding protein 4 by a specific insulin
      like growth factor binding protein 4 proteinase in normal human osteoblast-like
      cells: implications in bone cell physiology.
AB  - Insulin-like growth factor binding protein 4 (IGFBP-4) is secreted by normal
      human osteoblast-like cells (hOB) and is a potent inhibitor of insulin-like
      growth factor (IGF) action in vitro. In previous studies, IGF treatment of hOB in
      culture led to markedly reduced medium levels of IGFBP-4 as detected by western
      ligand blotting. In the present study, incubation of hOB-conditioned medium (hOB
      CM) with IGF under cell-free conditions resulted in a similar loss of IGFBP-4.
      Both IGF-I and IGF-II were capable of inducing a decrease in IGFBP-4; however,
      IGF-II was more effective. When the six characterized IGFBP were added to hOB-CM,
      only IGFBP-4 disappeared in response to IGF-II addition. This IGF-regulated loss
      of IGFBP-4 was inhibited by metalloproteinase inhibitors and appeared to be due
      to a proteinase that cleaved IGFBP-4 in 18 and 14 kD fragments identified by
      western immunoblotting. Conditioned media from eight of eight different donor hOB
      lines tested exhibited IGFBP-4 proteinase activity. To assess the biologic
      consequences of IGF-II-induced IGFBP-4 proteolysis, we treated hOB with IGF-II
      for 5 h, which decreased medium IGF-BP-4 by 70%, and then measured IGF-I and
      insulin stimulation of [3H]thymidine incorporation. IGF-II itself was not
      mitogenic and had no effect on insulin-stimulated [3H]thymidine incorporation.
      However, pretreatment of cultured hOB with IGF-II enhanced IGF-I-stimulated
      [3H]thymidine incorporation threefold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512305
TI  - pp60 c-src expression and activity in MG-63 osteoblastic cells modulated by PTH
      but not required for PTH-mediated adenylate cyclase response.
AB  - A role for pp60c-src) tyrosine kinase in bone resorption was recently
      demonstrated in vivo. However, it is not known whether expression of this
      ubiquitous tyrosine kinase is essential in osteoblasts or osteoclasts. In this
      work, we have examined the expression of c-src in osteoblast-like cells. We found
      that c-src was expressed in the MG-63 osteoblastic osteosarcoma cell line as
      assessed by immunocytochemistry. When MG-63 cells were treated for 30 minutes
      with parathyroid hormone (PTH), the levels of tyrosine phosphorylation of c-src
      were increased in comparison with the untreated control. On the other hand, no
      changes in total c-src protein were observed after PTH treatment. The increase in
      c-src tyrosine phosphorylation due to PTH treatment was paralleled by an increase
      in c-src tyrosine kinase activity. Calcitonin had no effect on c-src
      phosphorylation, c-src protein level, or tyrosine kinase activity. To determine
      if c-src tyrosine kinase was required for normal bone cell function and PTH
      responsiveness, osteoblastic cells were isolated from the calvaria of a src
      deficient mouse. The cyclic AMP response to PTH in this cell was identical to
      that seen in freshly isolated calvarial cells from normal mice. These results
      suggest that the activity of c-src in MG-63 cells is regulated by PTH as a result
      of tyrosine phosphorylation. Expression of src is not required for PTH
      responsiveness in osteoblastic cells as assessed by adenylate cyclase activation.
      The mode of signal transduction from the PTH receptor to nonreceptor c-src
      tyrosine kinase is not known at present.

PMID- 7512306
TI  - CD44 expression in human bone: a novel marker of osteocytic differentiation.
AB  - CD44 is a transmembrane glycoprotein with cell-cell and cell-matrix adhesion
      functions that is expressed by a wide variety of cell types and has a number of
      known biologic functions. Because of its ability to bind matrix macromolecules,
      such as fibronectin, collagen, and hyaluronate, we investigated the possibility
      that it is expressed by the cells of bone, the matrix receptors of which are
      largely unknown. Immunohistochemical study of a variety of sources of human bone
      was carried out using a panel of six well-characterized anti-CD44 monoclonal
      antibodies. Osteocytes strongly expressed CD44, whereas osteoblasts and lining
      cells were negative. Osteoclasts and periosteal cells also expressed CD44,
      although not as strongly as osteocytes. These patterns of staining were observed
      with all six antibodies. These results demonstrate that acquisition of CD44
      immunoreactivity is a sensitive marker of osteocytic differentiation and raise
      the possibility that CD44 acts as a cell matrix receptor in bone.

PMID- 7512307
TI  - Novel idea in BPH guideline: the patient as decision maker.

PMID- 7512308
TI  - Benign prostatic hyperplasia: diagnosis and treatment. Benign Prostatic
      Hyperplasia Guideline Panel. Agency for Health Care Policy and Research.

PMID- 7512310
TI  - Calmodulin immunoreactivity in the chicken pineal gland: comparison with
      calbindin-D28k, calretinin, and S100.
AB  - Calmodulin distribution in the chicken pineal organ was investigated by
      immunohistochemistry. Calmodulin immunoreactivity was detected in ependymocytes
      in the follicular zone and in interstitial cells in the parafollicular zone. No
      calmodulin immunoreactivity was detected in pinealocytes. Lack of calmodulin
      immunoreactivity in pinealocytes raises questions about its proposed function in
      melatonin synthesis as suggested by pharmacological studies using calmodulin
      antagonists. The calmodulin distribution was comparable to that of S100, a glial
      cell marker. Two other markers, calbindin-D28k and calretinin, which in
      neuroanatomical studies give excellent cytoarchitectonic staining, in the chick
      pineal permitted the detection of two subclasses of pinealocytes. One was darkly
      stained by calbindin-D28k and rare. The other was very abundant and calretinin
      positive. In the parafollicular zone, calbindin-D28k and/or calretinin antibodies
      allowed us to visualize cells presenting a neuron-like morphology. Calretinin
      immunoreactivity was detected in nearly all pinealocytes in which hydroxy-indol-O
      methyl transferase was also located. Comparison between the lack of calmodulin
      and the presence of calretinin, belonging to the same calcium-binding protein
      family, in chick pinealocytes raises the hypothesis about a possible role of
      calretinin in melatonin synthesis.

PMID- 7512309
TI  - Differential contribution of nitric oxide to regulation of vascular tone in
      coronary conductance and resistance arteries: intravascular ultrasound studies.
AB  - We examined the role of nitric oxide in the maintenance of coronary vascular tone
      in 15 dogs. A 0.014 inch Doppler wire was introduced into the midsegment of the
      circumflex coronary artery and a 4.3F, 30 MHz two-dimensional ultrasound imaging
      catheter was introduced over the Doppler wire. Acetylcholine caused a dose
      dependent vasodilation in both epicardial and resistance coronary arteries.
      However, N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric
      oxide synthetase caused a dose-dependent vasoconstriction mainly in the
      epicardial coronary arteries, partially reversed by L-arginine. The vasodilator
      response to acetylcholine was inhibited by L-NAME only in the epicardial
      circulation. Thus using combined intracoronary two-dimensional and Doppler
      ultrasound, we have demonstrated both basal and acetylcholine-induced release of
      nitric oxide in epicardial coronary arteries. The failure of L-NAME to decrease
      basal and acetylcholine-induced increases in flow velocity suggests that
      endothelium-dependent relaxation in coronary resistance vessels may not be
      mediated by nitric oxide alone.

PMID- 7512311
TI  - Development of an enzyme-linked immunosorbent assay for measurement of fire ant
      venom-specific IgE.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for in vitro
      measurement of IgE specific for Solenopsis invicta venom. Enhanced binding
      microtiter plates were coated with S. invicta venom protein and incubated with
      sera from fire ant allergic patients and control subjects. Bound IgE was tagged
      with peroxidase-conjugated monoclonal anti-IgE and quantitated with the
      substrate/indicator system H2O2/tetramethylbenzidine. Absorbance (620 nm)
      represented venom-specific IgE values. The ELISA correlated well with the
      imported fire ant venom RAST (r = .87, P < .0001). Using skin test reactivity as
      the standard measure of venom-specific IgE, the venom ELISA appeared to be a
      sensitive in vitro assay comparable to venom RAST. ELISA is less expensive than
      RAST and does not require licensing or handling of radioisotopes.

PMID- 7512312
TI  - A Head Start for the 21st century.
AB  - Social and economic conditions since the creation of Head Start in 1965 have
      worsened. The stresses of economic restructuring in America and the pervasiveness
      of violence have severely eroded the capacity of many families to provide safe
      and caring homes in strong communities. The necessary adaptation of Head Start to
      these new conditions involves the essential linkage of early childhood and family
      support approaches with community economic development. This strategy must
      include a reappraisal of mental health paradigms that will enable children,
      youth, and families to be healthy and productive members of their neighborhoods
      and country. Although public support for Head Start remains strong, considerable
      rethinking about a Head Start for the 21st century is now occurring; results will
      affect the quality of life for the entire society.

PMID- 7512313
TI  - Head Start. Only the best for America's children.
AB  - In March 1993 Senator Kassebaum introduced the Head Start Quality Improvement Act
      aimed at building on the success of Head Start by connecting a dramatically
      increased budget with measures designed to upgrade the quality of the program.
      The legislation provides the DHHS with the mandate, the resources, and the
      necessary legislative tools, using a five-part approach to (a) establish general
      performance measures for all grantees; (b) strengthen program accountability
      mechanisms, training, and technical assistance support systems; (c) provide more
      effective policy enforcement and instill more competition in the program; (d)
      expand the current Head Start Transition Project to assist children and their
      families in making a successful move from Head Start to elementary school; and
      (e) assist families entering or reentering the work force.

PMID- 7512314
TI  - Strengthening mental health services in Head Start. A challenge for the 1990s.
AB  - Steps must be taken to strengthen mental health services by building on Head
      Start's philosophy and by translating innovations in mental health services for
      older children and adolescents into improved services for young children and
      their families. Recommendations for strengthening Head Start's mental health
      program include creating a unified vision that reaffirms a holistic, family
      focused, and comprehensive services approach; ensuring that mental health
      services are responsive to the diversity in families served; increasing
      coordination of mental health services and linkages with new initiatives;
      increasing resources and providing assistance in gaining access to new sources of
      funding; supporting innovation; and integrating the new paradigm for children's
      mental health services into more traditional approaches to intervention within
      Head Start.

PMID- 7512315
TI  - Is the activity of the fusion pore scaffold regulated by a coincidence detector?

PMID- 7512316
TI  - Can exocytosis induced by alpha-latrotoxin be explained solely by its channel
      forming activity?

PMID- 7512317
TI  - In vitro stability of endogenous parathyroid hormone-related protein in blood and
      plasma.
AB  - We describe a systematic comparison of the effects of anticoagulants, protease
      inhibitors and conditions of sample handling on the in vitro stability of
      endogenous parathyroid hormone-related protein (PTHrP) in blood from patients
      with hypercalcaemia of malignancy (HM). When blood was separated within 15 min of
      collection, PTHrP1-86 levels measured by two-site immunoradiometric assay in
      serum and heparinized plasma were significantly lower than in
      ethylenediaminetetraacetic acid (EDTA) plasma (P < 0.02). PTHrP was unstable in
      blood kept at 20 degrees C for 4 h and inclusion of protease inhibitors reduced,
      but failed to abolish, this instability. In blood collected in the presence of
      EDTA, inclusion of leupeptin either alone or in combination with pepstatin and
      aprotinin increased the mean half-time of disappearance from 3.9 to 10.1 and 11.2
      h, respectively (P < 0.05). In contrast, when blood containing EDTA was separated
      within 15 min, PTHrP was stable in plasma at 20 degrees C for at least 4 h. As a
      result of the instability of PTHrP1-86 immunoreactivity in whole blood at ambient
      temperatures we advise that for our immunoradiometric assay (IRMA) blood
      collected in EDTA should be separated within 15 min, and the plasma frozen until
      assay.

PMID- 7512318
TI  - Serum insulin-like growth factor binding protein-1 in pregnant women: decreased
      concentrations following an oral glucose load.
AB  - Serum concentrations of insulin-like growth factor binding protein-1 (IGFBP-1)
      were measured in men and in non-pregnant and pregnant women. Peak serum IGFBP-1
      levels occurred mid-gestation followed by a slight decline towards term. Women
      with gestational diabetes had higher serum IGFBP-1 concentrations than apparently
      healthy women at comparable gestation. Following administration of an oral
      glucose load, serum IGFBP-1 concentrations were decreased within 2 h in men and
      in pregnant women while IGF-I levels remained constant. These results suggested
      that IGFBP-1 regulates IGF-I activity in pregnancy in a similar manner to that in
      the non-pregnant state.

PMID- 7512320
TI  - FK506-induced neurotoxicity in liver transplantation.
AB  - We report FK506-induced neurotoxicity in 14 of 44 consecutive patients following
      orthoptic liver transplantation. In 10 of these 14 patients, postural hand
      tremors were found in the first weeks following surgery, transient apraxia of
      speech in 3, and generalized tonic-clonic seizures were noted in 2 patients.
      Other manifestations included nightmares, agitation, and acute delirium.
      Reduction of the FK506 dose resulted in resolution of symptoms, but in 1 patient
      mild speech difficulties and in 3 patients a fine tremor remained. Blood and
      plasma levels of FK506 were similar in patients with and without neurotoxicity.
      FK506 neurotoxicity in patients with liver transplantation commonly results in
      transient neurological manifestations. The incidence of neurotoxicity in FK506 is
      dramatically reduced in maintenance doses of 0.075 mg/kg twice a day.

PMID- 7512319
TI  - Elevated expression of messenger RNA for peripheral myelin protein 22 in biopsied
      peripheral nerves of patients with Charcot-Marie-Tooth disease type 1A.
AB  - The human peripheral myelin protein 22 (PMP-22) gene has been mapped to
      chromosome 17p11.2 in the duplicated region associated with Charcot-Marie-Tooth
      disease type 1A. Southern blot analysis using PMP-22 as a probe indicated that
      the PMP-22 gene was duplicated in 5 patients from unrelated Japanese families
      with Charcot-Marie-Tooth disease type 1. In order to investigate whether or not
      an extra copy of PMP-22 has an effect on its gene expression, we analyzed
      relative expression of messenger RNA for PMP-22 and protein 0 (P0) against beta
      actin by Northern blotting in biopsied nerves of the patients with type 1A
      disease, and compared the results with those of patients having other
      demyelinating neuropathies and the autopsied nerves of patients without
      neuropathies. The relative expression of PMP-22 messenger RNA in 5 patients with
      Charcot-Marie-Tooth disease type 1A was significantly higher than that in 5
      patients with other demyelinating neuropathies (p < 0.05). There was no
      statistically significant difference in P0 expression between them. This study
      provided direct evidence for elevated expression of PMP-22 in peripheral nerves
      of patients with Charcot-Marie-Tooth disease type 1A as the result of a gene
      dosage effect. However, the relation between elevated expression of PMP-22 and
      the mechanism causing demyelination remains undetermined.

PMID- 7512321
TI  - [Apoptosis in immunology].
AB  - Apoptosis is the physiological cell death, and recent studies have revealed that
      apoptosis plays an important role in the various fields of immunology.
      Especially, in the formation of T or B cell repertoires, the cells reactive to
      self antigens are eliminated by the induction of apoptosis, whereas the cells
      competent to react against foreign antigens are saved for survival by the
      suppression of apoptosis. Furthermore, apoptosis is employed as the destruction
      mechanism of target cells in killer T cells or NK cells. The disturbance of
      apoptosis-mechanism, therefore, will be strongly relevant for the etiology of
      autoimmune diseases and carcinogenesis.

PMID- 7512322
TI  - Randomised trial of early tapping in neonatal posthaemorrhagic ventricular
      dilatation: results at 30 months. Ventriculomegaly Trial Group.
AB  - One hundred and fifty seven infants with progressive ventricular dilatation after
      intraventricular haemorrhage were randomised to either early repeated
      cerebrospinal fluid tapping or conservative management. Thirty two (20%) infants
      died and 13 (8%) were lost to follow up. One hundred and twelve children (90% of
      survivors) were examined at 30 months by a single experienced examiner. Overall,
      54 (48%) scored less than 70 on the Griffiths developmental scales, 101 (90%) had
      neuromotor impairment, and 85 (76%) had marked disability; 63 (56%) had multiple
      impairments. Vision was severely affected in 10 (9%) and 30 (27%) had a field
      defect. Six per cent (seven children) had sensorineural hearing loss and 16 (14%)
      were taking regular anticonvulsant drugs. Although early cerebrospinal fluid
      tapping reduced the rate of ventricular and head expansion, there was no
      statistically significant difference (at the 5% level) between the treatment
      groups in the prevalence of neuromotor impairments, non-neuromotor impairments,
      nor multiple impairments at 30 months. These findings were consistent regardless
      of the presence or absence of a parenchymal cerebral lesion at entry to the
      trial. In the light of these findings and the 7% risk of cerebrospinal fluid
      infection associated with repeated tapping, this form of early intervention
      cannot be recommended.

PMID- 7512323
TI  - Reappraisal of in situ immunophenotypic analysis of psoriasis skin: interaction
      of activated HLA-DR+ immunocompetent cells and endothelial cells is a major
      feature of psoriatic lesions.
AB  - Psoriasis is an inflammatory skin disease of unknown aetiology. Many observations
      indicate that T cells play an important role in the pathogenesis of the disease.
      Upregulation of MHC class-II molecules on immunocompetent cells, endothelial
      cells and keratinocytes on lesional psoriatic skin has been regarded as a
      hallmark of the disease. However, there is some controversy in the literature
      regarding the cell types expressing class-II molecules and there is limited
      information about the presence of immune cells other than T cells and antigen
      presenting cells in the cellular infiltrates of psoriatic skin. We therefore
      reinvestigated the subject using immunocytochemical single and multiple staining
      techniques. In agreement with earlier reports, our studies showed that the
      cellular infiltrates in lesional skin consist largely of HLA-DR+/IL-2R+ T cells,
      HLA-DR+/CD1a+ Langerhans cells, and HLA-DR+/CD68+ macrophages. We found increased
      HLA-DR expression mostly on immuno-competent cells and endothelial cells, but no
      prominent HLA-DR expression on keratinocytes in lesional psoriatic skin.
      Upregulation of HLA-DR on endothelial cells and in mononuclear infiltrates was
      also evident in the non-lesional skin of psoriatic patients as compared with
      normal controls. B cells and natural killer cells were also found in the cellular
      infiltrates in lesional psoriatic skin. In spite of the presence of a large
      amount of activated T cells in the epidermis, we found that HLA-DR expression on
      keratinocytes was not a major feature of psoriatic skin.

PMID- 7512324
TI  - HLA nomenclature: a user-friendly system?

PMID- 7512325
TI  - G-CSF in gold-induced aplastic anaemia.

PMID- 7512327
TI  - [Combined viral-mycoplasma placentitis].
AB  - 265 placentas were studied by means of light and fluorescent microscopy. 82
      placentas showed combined infections induced by 2-5 agents (various viruses and
      mycoplasmas). Bacterial and fungal placentitis were excluded Manifestations
      depended on the infectious agents, their number and variants of their
      combination. Enhancement of vascular damage was observed in placentitis with
      participation of myxoviruses and herpes simplex virus. Enhancement of
      lymphoplasmacytic infiltration and sclerosis was typical for combined placentitis
      as well as alteration of antibody formation and interferon production. This
      reflects the gravity of the infection and its spread to the extra-placental
      membranes.

PMID- 7512326
TI  - Shifting proportions of gastric adenocarcinomas.
AB  - OBJECTIVES: To substantiate reports of increasing proportions of gastric
      adenocarcinoma of diffuse histologic type and in the proximal portion of the
      stomach, to better understand the prognostic features that govern survival, and
      to determine whether alterations of operative strategy might improve the surgical
      results. DESIGN: Retrospective analysis of 289 consecutive patients with gastric
      adenocarcinoma operated on by general surgeons over a 26-year period. Records
      were reviewed for location, histologic type, resection, operative mortality,
      lymph node status, and outcome. SETTING: The Section of Surgical Oncology, the
      New England Deaconess Hospital, Boston, Mass. MAIN OUTCOME MEASURES: Survival
      rate, length of life of the patients who died, and operative mortality. RESULTS:
      A marked and significant shift of gastric adenocarcinoma to a proximal location
      (54% between 1985 and 1990) occurred over 26 years (P = .0075) with a significant
      stage improvement at presentation (P = .0235). Percentages of cancers that were
      of the diffuse, poorly differentiated histologic type increased to 48%. More
      curative operations were performed in the last period (61%), and this upward
      trend from 37% was significant. Proximal gastric cancers had a poorer prognosis
      with more operative deaths, more lymph node metastases, and worse survival rates
      than distal cancers. Poor survival rates occurred even when comparing patients
      with negative lymph nodes or favorable histologic features with patients with
      similar distal cancers. CONCLUSIONS: Despite significant increases in the
      proportion of proximal cancers, survival rates have improved only slightly. Nodal
      status plays a less prognostic role than does location or histologic type but
      does provide prognostic information for individual locations. Survival rates for
      diffuse histologic cancer were consistently worse than those for intestinal
      histologic cancer, which emphasizes the underlying disease biology controlling
      outcome. Radical lymphadenectomy for gastric adenocarcinoma would not improve
      surgical outcome in the United States.

PMID- 7512328
TI  - [Early hemodynamic effects of the rapid infusion of sodium chloride Dextran-70
      hypertonic solution as treatment for hemorrhagic shock in dogs].
AB  - PURPOSE: To study the early hemodynamic effects of the rapid infusion of 7.5g/dl
      NaCl/ 6g/dl dextran-70 solution in dogs submitted to hemorrhagic shock. METHODS:
      Mongrel dogs were anesthetized with pentobarbital and a electromagnetic flowmeter
      probe was placed around the ascending aorta or the portal vein. By external
      bleeding the arterial pressure was lowered to 40mmHg and held for 30min. The
      animals received a 4ml/kg infusion of the hypertonic solution in 90s. Arterial
      blood pressure and flow were registered continuously during 3min and the derived
      hemodynamic variables were calculated at regular time intervals. RESULTS: The
      total plasma protein concentration decreased and the cardiac output showed a
      continuous elevation during the infusion. The arterial blood pressure showed two
      oscillations and then decreased during a short period of time. This moment was
      coincident with the initial increase of the portal flow and preceded the
      elevation of the systemic vascular resistance and the arterial pressure.
      CONCLUSION: The rapid infusion of hypertonic NaCl/dextran solution to dogs in
      hemorrhagic shock determines immediate and intense hemodynamic effects. During
      the infusion period there is volemic expansion and the cardiac output increases
      rapidly. The arterial pressure shows oscillations and decreases as a consequence
      of visceral arterial dilation before starting its final elevation that occurs as
      the vascular resistance increases.

PMID- 7512329
TI  - Race, macular degeneration, and diabetic maculopathy.

PMID- 7512330
TI  - Should we recommend vitreous surgery for patients with choroidal
      neovascularization?

PMID- 7512331
TI  - A new standard of care for laser photocoagulation of subfoveal choroidal
      neovascularization secondary to age-related macular degeneration. Data revisited.

PMID- 7512332
TI  - A pilot study of indocyanine green videoangiography-guided laser photocoagulation
      of occult choroidal neovascularization in age-related macular degeneration.
AB  - PURPOSE: To evaluate the use of digital indocyanine green videoangiography in
      patients with clinical and fluorescein angiographic evidence of "occult"
      choroidal neovascularization in age-related macular degeneration and to
      investigate indocyanine green videoangiography-guided laser photocoagulation as a
      therapeutic approach. METHODS: Three hundred forty-seven consecutive patients
      with exudative age-related macular degeneration and symptoms and clinical
      manifestations of occult choroidal neovascularization were studied with
      indocyanine green videoangiography. Patients were selected for laser treatment,
      using conventional guidelines, when indocyanine green videoangiography
      demonstrated a well-delineated area of hyperfluorescence, presumed to be a focal
      area of choroidal neovascularization. RESULTS: Seventy-nine (23%) of 347 eyes
      were found to have a localized and definable lesion that was potentially amenable
      to laser photocoagulation therapy; 44 (56%) of these 79 treated eyes had complete
      resolution of their exudative manifestations. Visual acuity improvement was noted
      in 10 (13%) of 79 eyes, and stabilization of vision achieved in 42 eyes (53%).
      CONCLUSION: Laser photocoagulation treatment guided by indocyanine green
      videoangiography was shown to produce promising anatomical and visual improvement
      in a small number of patients with occult choroidal neovascularization secondary
      to age-related macular degeneration. This pilot study warrants further research
      to investigate the efficacy and safety of this form of treatment.

PMID- 7512333
TI  - A pilot study of digital indocyanine green videoangiography for recurrent occult
      choroidal neovascularization in age-related macular degeneration.
AB  - PURPOSE: Digital indocyanine green videoangiography (ICG-V) was used to study
      recurrent choroidal neovascularization (CNV) in patients with the clinical and
      fluorescein angiographic findings indicative of ill-defined, or recurrent occult,
      CNV (RO-CNV). The use of ICG-V-guided laser caphotocoagulation as an alternative
      form of treatment was also investigated when a well-delineated area of CNV was
      imaged with this technique. METHODS: A consecutive series of 66 patients were
      studied who presented with exudative age-related macular degeneration and
      symptoms and clinical manifestations of recurrent CNV in which fluorescein
      angiography did not reveal classic, or well-defined, neovascularization. Patients
      were selected for laser treatment based on conventional guidelines if ICG-V
      imaged a well-delineated area of recurrent CNV. RESULTS: Indocyanine green
      videoangiography showed late staining that was consistent with recurrent CNV in
      64 (97%) of these 66 patients with RO-CNV. Twenty-nine (44%) of the 66 were
      eligible for laser treatment, and 18 (62%) of these 29 patients experienced
      successful anatomic and visual results, which were defined as resolution of the
      exudative manifestations and improvement or stabilization (+/- 1 line on a
      Snellen chart) of vision. CONCLUSIONS: This pilot study suggests that ICG-V is of
      value in imaging patients with RO-CNV after laser photocoagulation for CNV
      secondary to age-related macular degeneration. Laser treatment of RO-CNV with ICG
      V guidance may be successful both anatomically and functionally in a promising
      number of these otherwise untreatable cases. Further studies are necessary to
      validate these preliminary findings.

PMID- 7512334
TI  - Visual outcome after laser photocoagulation for subfoveal choroidal
      neovascularization secondary to age-related macular degeneration. The influence
      of initial lesion size and initial visual acuity. Macular Photocoagulation Study
      Group.
AB  - OBJECTIVE: To provide detailed information specific to the initial visual acuity
      and initial lesion size on the outcome of patients with subfoveal choroidal
      neovascularization (CNV) secondary to age-related macular degeneration. DESIGN
      AND PATIENTS: The 189 eyes assigned to laser photocoagulation and the 184 eyes
      assigned to observation in the Subfoveal New CNV Study were divided into nine
      subgroups based on initial visual acuity and initial lesion size. MAIN OUTCOME
      MEASURES: The pattern of visual acuity loss for both treated and untreated eyes
      through 4 years of follow-up was compared among the subgroups. Reading speed and
      contrast thresholds also were examined. RESULTS: Four patterns (A, B, C, D) of
      visual acuity loss in treated eyes relative to untreated eyes were identified.
      Eyes in group A (small lesion and moderate or poor initial visual acuity or
      medium lesion and poor visual acuity) had the best visual outcome with treatment;
      treated eyes were better throughout follow-up. Eyes in group B (small lesion and
      good initial visual acuity or medium lesion and moderate or good visual acuity)
      had substantial treatment benefit by 12 months, but were worse immediately after
      treatment. Eyes in group C (large lesion and poor initial visual acuity) had a
      small treatment benefit throughout follow-up. Eyes in group D (large lesion and
      moderate or good visual acuity) had the worst visual outcome with treatment;
      treated eyes were substantially worse for the first 18 months and were not
      appreciably better through 4 years of follow-up. CONCLUSIONS: Recommendations for
      treatment of subfoveal CNV should take account of the initial visual acuity and
      lesion size. Eyes in group D are poor candidates for laser treatment.

PMID- 7512335
TI  - Persistent and recurrent neovascularization after laser photocoagulation for
      subfoveal choroidal neovascularization of age-related macular degeneration.
      Macular Photocoagulation Study Group.
AB  - OBJECTIVE: To determine the incidence and visual impact of and risk factors for
      persistent and recurrent neovascularization after laser photocoagulation of
      subfoveal choroidal neovascularization (CNV) in patients with age-related macular
      degeneration. DESIGN, PATIENTS, AND METHODS: The records of 189 eyes in the
      Subfoveal New CNV Study and 100 eyes in the Subfoveal Recurrent CNV Study
      assigned to laser photocoagulation were examined. Persistent CNV (detected within
      6 weeks of treatment) and recurrent CNV (detected after 6 weeks) were defined
      angiographically by fluorescein leakage from the periphery of the treatment scar.
      Incidence was estimated using survival analysis methods. RESULTS: In both
      studies, persistent CNV was observed in approximately 13% of the eyes, and
      recurrent CNV was estimated to have developed by 3 years in an additional 35% of
      the eyes. In the New CNV Study, by 3 years, 36% of the eyes with persistent CNV
      had lost 6 or more lines of visual acuity as had 19% of the eyes with recurrent
      CNV and 27% of the eyes without persistence or recurrence. The presence of
      neovascular maculopathy in the fellow eye was associated with an increased risk
      for persistence or recurrence in the study eye. In the New CNV Study, partial
      coverage of the lesion with heavy laser treatment and/or runoff was associated
      with increased risk for persistence; less extensive natural scarring of the
      lesion at study entry was associated with increased risk for recurrence.
      CONCLUSIONS: Close to half of the eyes treated for subfoveal CNV have persistent
      or recurrent CNV within 3 years. There is a strong association between
      neovascular maculopathy in the fellow eye and the inability of laser
      photocoagulation to permanently obliterate signs of CNV from the study eye.
      Within these two studies, there was little additional damage to visual function
      resulting from persistent or recurrent neovascularization. There appears to be no
      reason to deviate from the protocol goal of covering the entire neovascular
      complex when treating eyes with subfoveal CNV.

PMID- 7512336
TI  - Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year
      results from randomized clinical trials. Macular Photocoagulation Study Group.
AB  - OBJECTIVE: To summarize findings from three randomized clinical trials of krypton
      laser treatment of juxtafoveal neovascular lesions regarding changes in visual
      acuity during 5 years of follow-up, rates of persistent and recurrent choroidal
      neovascularization, and status of macular lesions 5 years after enrollment.
      DESIGN, PATIENTS, AND PRIMARY OUTCOME MEASURES: Follow-up of patients enrolled in
      three randomized trials of choroidal neovascularization secondary to age-related
      macular degeneration (AMD), ocular histoplasmosis, or idiopathic causes ended in
      March 1991. All patients were eligible to complete at least 3 years of follow-up
      examinations. Data on visual acuity, reading vision, and anatomic outcomes during
      5 years of follow-up were available for 276 (92%) of 300 patients with AMD, 236
      (92%) of 256 patients with ocular histoplasmosis, and 38 (97%) of 39 patients
      with idiopathic choroidal neovascularization enrolled 5 or more years earlier who
      were still living. RESULTS: Among eyes with AMD, the estimated relative risk (RR)
      of a loss of 6 or more lines of visual acuity from baseline to any examination
      from 6 months through 5 years after enrollment for untreated eyes in comparison
      with treated eyes was 1.20 (P = .04). Normotensive patients with AMD realized the
      greatest benefit from laser treatment (RR, 1.82) and hypertensive patients
      experienced little or no benefit (RR, 0.93). Untreated eyes with ocular
      histoplasmosis were at much greater risk of a 6-line decrease in visual acuity
      from the 1-year through the 5-year examination than were treated eyes (unadjusted
      RR, 2.60; RR, 4.26 after adjustment for visual acuity and hypertension at
      baseline; P < .001 for both). The treatment effect for eyes with idiopathic
      choroidal neovascularization was between the effects for eyes with AMD and eyes
      with ocular histoplasmosis. CONCLUSIONS: The early beneficial effects of laser
      treatment on visual acuity persisted for at least 5 years in eyes with all three
      underlying conditions. Laser treatment of similar eyes with choroidal
      neovascularization in a juxtafoveal location is recommended for patients with
      these conditions, with the caveat that hypertensive patients with AMD may fare no
      better with laser treatment than without treatment.

PMID- 7512337
TI  - Hydration changes in cadaver eyes prepared for practice and experimental surgery.
AB  - OBJECTIVES: To identify reliable and efficient methods of thinning postmortem
      corneas for surgical experiments and to develop methods of maintaining stable
      corneal thickness. METHODS: Three methods of corneal thinning were evaluated by
      group: group A, increased intraocular pressure; group B, exchange of anterior
      chamber fluid with dextran solution and immersion in dextran solution; and group
      C, immersion in dextran solution without aqueous replacement. The stability of
      the thinned central cornea was then evaluated by exposing 30 corneas thinned by
      methods used in groups B and C to air, Balanced Salt Solution drops (Alcon, Fort
      Worth, Tex), or dextran solution drops. RESULTS: By 1 hour, the thinning method
      used in group A resulted in only three of 11 eyes achieving normal central
      corneal thickness. The method used in group B resulted in normal central
      thickness in 14 of 14 corneas and in group C, in nine of 15 corneas, at 1 hour.
      Once thinned by methods used in group B or C, air exposure further thinned the 30
      additional corneas by 22% to 26%, Balanced Salt Solution drops thickened the
      corneas by 16% to 22%, and dextran solution drops stabilized the corneas with
      only 5% to 13% additional thinning. CONCLUSIONS: Hyperosmolar solutions were more
      efficient than pressure gradients in thinning the cadaver central cornea.
      Hydration shifts of the de-epithelialized cornea were dramatic with use of
      Balanced Salt Solution drops or drying and were minimized with use of
      hyperosmolar topical solutions.

PMID- 7512338
TI  - Localization and solubilization of hyaluronan and of the hyaluronan-binding
      protein hyaluronectin in human normal and arteriosclerotic arterial walls.
AB  - Hyaluronectin (HN), a hyaluronan (hyaluronic acid, HA)-binding glycoprotein
      isolated from human brain, was studied in normal and atherosclerotic human
      arteries. It can be detected and assayed in tissue samples by
      immunohistochemistry. In addition, its high and specific affinity for HA makes it
      possible to develop specific histological localization of HA using HN as a probe.
      We tested the presence of HN and HA in human carotid artery samples from adults
      and newborns. In atheroma-free arterial samples HN was found in the intima,
      between smooth muscle cells and in the adventitial extracellular matrix. In
      atherosclerotic lesions, HN was strongly expressed in the diffuse thickened
      intima and surrounding extracellular microcrystalline calcium deposits, and very
      little in the lipid core. HA was found in the same locations. The similar
      localizations of HN and HA shown by immunohistology and demonstration of HN-HA
      complexes by high pressure liquid chromatography (HPLC) suggest that they are
      associated in vivo.

PMID- 7512339
TI  - Economy of acid-base balance and oxygenation with progressive fetal anemia.

PMID- 7512340
TI  - Oxygenation of the human fetus as a function of hemoglobulin concentration.
AB  - We studied the relationships between fetal hemoglobin concentration, acid base
      status, and lactate concentration in umbilical venous and fetal heart blood in
      157 fetuses affected by blood group incompatibility who had been exposed for 214
      fetal blood sampling procedures (cordocentesis in 153 and intracardiac puncture
      in 61 cases). All blood samplings were obtained before fetal blood transfusions
      were administered. The results indicate that the human fetus can maintain a
      normal acid-base status until a 50% reduction of the hemoglobin concentration. A
      further reduction of hemoglobulin is associated with an accumulation of lactate
      both in umbilical venous and fetal heart blood. The partial oxygen tension and
      the oxygen saturation in umbilical venous blood remained virtually unchanged with
      decreasing hemoglobin concentration (r = -0.11, P = 0.21; r = 0.09, P = 0.31,
      respectively), whereas these parameters decreased significantly (r = 0.33, P =
      0.02; r = 34, P = 0.02) in blood obtained from the fetal heart. The partial
      carbon dioxide tension of umbilical vein blood decreases significantly with a
      reduced hemoglobin concentration (r = 0.25 P = 0.008). We speculate that these
      alterations in acid-base status in umbilical vein and fetal heart blood reflect a
      circulatory transition from a high to a low cardiac output as the hemoglobin
      concentration decreases.

PMID- 7512341
TI  - Heterogeneity in cellular and antibody responses against thyrotropin receptor in
      patients with Graves' disease detected using synthetic peptides.
AB  - Graves' disease (GD) is characterized by the presence of autoantibodies to the
      thyrotropin receptor (TSHr). These antibodies bind to the TSHr and stimulate
      thyroid cells, thus causing hyperthyroidism. To understand the regulation of TSHr
      specific immune responses in Graves' disease, it is important to evaluate the T
      cell response in patients with GD against TSHr. In this study we used 11
      different peptides that were derived from two regions (i.e. amino acid, AA 12-46
      and 316-397) unique to the TSHr when compared to other glycoprotein hormone
      receptors, and which also have the highest predicted immunogenicity. We evaluated
      both lymphocyte proliferation as a measure of T-cell response and antibody
      binding to each of these peptides in nine patients with GD and eight healthy
      subjects. Patients with GD showed considerable lymphocyte proliferative and
      antibody responses against several of these peptides. There was considerable
      heterogeneity in immune responses amongst the patients. Moreover, our data
      suggested that several peptides contained both T cell and antibody reactive
      epitopes and might represent some of the highly immunogenic regions of the TSHr.

PMID- 7512342
TI  - The acute phase response.
AB  - Adult mammals respond to tissue damage by implementing the acute phase response,
      which comprises a series of specific physiological reactions. This review
      outlines the principal cellular and molecular mechanisms that control initiation
      of the tissue response at the site of injury, the recruitment of the systemic
      defense mechanisms, the acute phase response of the liver and the resolution of
      the acute phase response.

PMID- 7512343
TI  - Immunotherapy of autoimmune disease with synthetic peptides.

PMID- 7512344
TI  - [Importance of the protein profile in internal medicine].
AB  - Until recent years, main biologic markers of inflammation used in current
      practice were limited to erythrocyte sedimentation rate, fibrinogen, and serum
      protein electrophoresis. A better understanding of inflammatory mechanisms and
      improvement of laboratories technologies helped in better understanding of the
      role and potential usefulness of inflammatory reaction proteins. Arrival of
      proteic profile and, more recently, the development of automation, still improved
      analysis of variations of different inflammatory reaction proteins. These
      proteins are then analyzed as an element of a "functional biological system",
      with known and so expected kinetics and ranges. The analyze of proteic profile
      combines the analyze of proteins variations, with elected but not exclusive
      associations, as Immunoglobulins and Complement, Orosomucoid and Haptoglobin, or
      Albumin and Transferrin. In Internal Medicine, proteic profile may help in
      solving daily problems. These problems may be so schematized: when the
      fundamental pathology is not yet known in an unraveling check-up, facing clinical
      symptoms, with a normal or fewly disrupted usual biologic panel, proteic profile
      may help to choose investigations necessary for the diagnosis; in the follow-up
      of patients treated for known inflammatory pathology facing new symptoms, part
      has to be done between complication of the disease and/or of the treatment, new
      pathology associated or unefficiency of the treatment. We report herein part of
      our experience of proteic profile in an Internal Medicine department, from some
      particularly demonstrative case reports: congenital or acquired abnormality of
      iron metabolism, with normal usual iron panel (iron deficiency, hemochromatosis);
      severe evolutive inflammatory or infectious disease with normal erythrocyte
      sedimentation rate (temporal arteritis, infectious endocarditis).

PMID- 7512346
TI  - [In vitro sensitivity of accessory hematopoietic cells from neutropenic subjects
      to the activity of human gamma-globulin].
AB  - We studied eight patients all showing neutropenia: drug-induced isolated
      neutropenic failure (2 cases), immune cell-mediated neutropenia (2 case), severe
      bone marrow hypoplasia (2 cases), dysmyelopoietic syndrome (1 case), cyclic
      neutropenia (1 case). Aim of the study was to assay the effect on CSA production
      of the pretreatment of autologous peripheral blood mononucleated cells (APBMN)
      with immunoglobulins (Ig). The CFU-GM growth were tested in different
      experimental conditions: with standard source of CSA, with autologous source,
      with autologous source modified by means of the preincubation of the autologous
      cells with Ig. The bone marrow CFU-GM culture was performed by Pike and
      Robinson's double layer agar technique. The experimental data were pointed out
      with topographic lecture of the dishes repeated at two times so as to obtain
      besides the aggregates global growth their dynamic classes too. We observed that
      the APBMN cells pretreatment with Ig modulates CSA production: represses it in
      cases showing high production and increases it in those showing low production.
      The effect of Ig modulation appears clearer on the GM-progenitor proliferating
      late (AC-C) than on those proliferating early (AC-A). This effect turned out to
      be particularly evident in a case with immune cell-mediated neutropenia and in
      both cases with drug-neutropenia. We retain that the monomers Ig could block Fc
      receptors and modulate their expression on macrophagic cells, conditioning in
      this way the CSA production. The parenteral administration of intact Ig (in vivo
      treatment of the APBMN cells) appears therefore helpful both in cases with CSA
      defect and in cases with excess of CSA production.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7512345
TI  - [EEG and autonomic effects of centrally administered galanin in the rabbit].
AB  - The effects of centrally administered galanin (10 and 20 mcg) on the EEG, somatic
      behaviour and some autonomic parameters have been studied in unanesthetized
      rabbits. In this species the peptide induced a dose related increase in
      electrocortical power spectrum density and behavioural sedation. Autonomic
      changes, consisting in moderate hyperthermia and bradypnea, were seen only after
      the highest dose of the peptide. These data support a central action of the
      peptide and suggest a role for galanin as sedative neuropeptide.

PMID- 7512347
TI  - [Co-involvement of catecholaminergic and gabaergic transmission in the electro
      cortical response to central galanin administration in the rabbit].
AB  - The involvement of catecholaminergic and gabaergic transmission in the
      electrocortical pattern induced by centrally administered galanin was
      investigated in the rabbit. The inhibition of catecholamine synthesis by both DDC
      and alphaMPT potentiated the EEG effect of the peptide. Baclofen and muscimol
      significantly enhanced the EEG response to GAL. However the interaction between
      the peptide and gabaergic transmission seemed mainly to involve the type A
      receptor system.

PMID- 7512348
TI  - Coupling of CFTR Cl- channel gating to an ATP hydrolysis cycle.
AB  - For cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels to
      open, they must be phosphorylated by protein kinase A and then exposed to a
      hydrolyzable nucleoside triphosphate, such as ATP. To test whether channel
      opening is linked to ATP hydrolysis, we applied VO4 and BeF3 to CFTR channels in
      inside-out patches excised from cardiac myocytes. These inorganic phosphate
      analogs interrupt ATP hydrolysis cycles by binding tightly in place of the
      released hydrolysis product, inorganic phosphate. The analogs acted only on CFTR
      channels opened by ATP and locked them open, increasing their mean open time by 2
      3 orders of magnitude. These findings establish that opening and closing of CFTR
      channels are coupled to an ATP hydrolysis cycle.

PMID- 7512349
TI  - Developmental and regional expression in the rat brain and functional properties
      of four NMDA receptors.
AB  - An in situ study of mRNAs encoding NMDA receptor subunits in the developing rat
      CNS revealed that, at all stages, the NR1 gene is expressed in virtually all
      neurons, whereas the four NR2 transcripts display distinct expression patterns.
      NR2B and NR2D mRNAs occur prenatally, whereas NR2A and NR2C mRNAs are first
      detected near birth. All transcripts except NR2D peak around P20. NR2D mRNA,
      present mainly in midbrain structures, peaks around P7 and thereafter decreases
      to adult levels. Postnatally, NR2B and NR2C transcript levels change in opposite
      directions in the cerebellar internal granule cell layer. In the adult
      hippocampus, NR2A and NR2B mRNAs are prominent in CA1 and CA3 pyramidal cells,
      but NR2C and NR2D mRNAs occur in different subsets of interneurons. Recombinant
      binary NR1-NR2 channels show comparable Ca2+ permeabilities, but marked
      differences in voltage-dependent Mg2+ block and in offset decay time constants.
      Thus, the distinct expression profiles and functional properties of NR2 subunits
      provide a basis for NMDA channel heterogeneity in the brain.

PMID- 7512350
TI  - Premature arrest of myelin formation in transgenic mice with increased
      proteolipid protein gene dosage.
AB  - Proteolipid protein (PLP) is an integral membrane protein of CNS myelin.
      Mutations of the X chromosome-linked PLP gene cause glial cell death and myelin
      deficiency in jimpy mice and other neurological mutants. As part of an attempt to
      rescue these mutants by transgenic complementation, we generated normal mouse
      lines expressing autosomal copies of the entire wild-type PLP gene. Surprisingly,
      increase of the PLP gene dosage in nonmutant mice with only 2-fold
      transcriptional overexpression results in a novel phenotype characterized by
      severe hypomyelination and astrocytosis, seizures, and premature death. This
      demonstrates that precise control of the PLP gene is a critical determinant of
      terminal oligodendrocyte differentiation. Dysmyelination of PLP transgenic mice
      provides experimental evidence that Pelizaeus-Merzbacher disease, previously
      associated with a partial duplication of the human X chromosome, can be caused by
      doubling of the PLP gene dosage.

PMID- 7512351
TI  - SV40 large T antigen with c-Jun down-regulates myelin P0 gene expression: a
      mechanism for papovaviral T antigen-mediated demyelination.
AB  - Expression of myelin proteins has been shown to be altered in transgenic mice
      that express papovaviral large tumor (T) antigens. This paper analyzes the effect
      on P0 gene expression in secondary Schwann cells transfected with the SV40 T
      antigen gene and in Schwann cells immortalized by T antigen. In secondary Schwann
      cells, both T antigen and c-Jun are required for significant inhibition of the P0
      promoter; expression of only one of the proteins is insufficient for repression
      of the P0 gene. T antigen, c-Jun (p39), and c-Jun-related protein (p47) form an
      immunoprecipitable complex in SV40 immortalized Schwann cell lines, and T antigen
      and c-Jun bind independently and as a complex to the P0 promoter. Our data
      suggest that the probable molecular mechanism underlying the hypomyelination
      observed in transgenic animals expressing T antigen may be due to the repression
      of the P0 gene by T antigen and c-Jun.

PMID- 7512352
TI  - Calcium-induced calcium release in cerebellar Purkinje cells.
AB  - Depolarization-induced intracellular Ca2+ rises were measured in fura-2-loaded,
      voltage-clamped Purkinje cells. The peak Ca2+ rise increased more than linearly
      with voltage step duration, suggesting the presence of Ca(2+)-induced Ca2+
      release. In cells from young animals, in which Ca2+ currents could be
      satisfactorily recorded, a supralinear relation was also found between peak Ca2+
      rise and Ca2+ current integral. Responses to long pulses were inhibited in cells
      dialyzed with 20 microM ruthenium red and potentiated in cells bathed in the
      presence of 20 microM ryanodine. Upon repetitive depolarization, increasing Ca2+
      rises were elicited by successive voltage pulses, probably because of a
      potentiating effect of residual Ca2+. Altogether, the results indicate an
      important contribution of Ca(2+)-induced Ca2+ release to Ca2+ signals of Purkinje
      cells.

PMID- 7512354
TI  - [Vital preservation of cartilaginous transplants using tissue culture
      procedures].

PMID- 7512355
TI  - Lindane haematotoxicity confirmed by in vitro tests on human and rat progenitors.
AB  - Blood dyscrasias such as aplastic anaemia and leukopenia are described following
      the use of lindane for agricultural purposes or against ectoparasites in animal
      and human health. In order to determine the involvement of lindane in these
      effects, an in vitro model of haematotoxicity evaluation has been used. Culture
      of haematopoietic progenitors, Colony Forming Unit-Granulocyte and Macrophage
      (CFU-GM), have been performed in the presence of lindane with increasing
      concentrations. Results showed that lindane was cytotoxic for human progenitors.
      They were one thousand times more sensitive to the lindane than rat CFU-GM. This
      cytotoxicity was observed with lindane concentrations similar to those measured
      in human blood in cases of acute intoxication and in fat tissues of exposed
      populations.

PMID- 7512353
TI  - TAG-1 can mediate homophilic binding, but neurite outgrowth on TAG-1 requires an
      L1-like molecule and beta 1 integrins.
AB  - Subsets of axons in the embryonic nervous system transiently express the
      glycoprotein TAG-1, a member of the subfamily of immunoglobulin (Ig)-like
      proteins that contain both C2 class Ig and fibronectin type III domains. TAG-1 is
      attached to the cell surface by a glycosylphosphatidylinositol linkage and is
      secreted by neurons. In vitro studies have shown that substrate-bound TAG-1
      promotes neurite outgrowth. We have examined the nature of axonal receptors that
      mediate the neurite-outgrowth promoting properties of TAG-1. Although TAG-1 can
      mediate homophilic binding, neurite outgrowth on a substrate of TAG-1 does not
      depend on the presence of TAG-1 on the axonal surface. Instead, neurite outgrowth
      on TAG-1 is inhibited by polyclonal antibodies directed against L1 and,
      independently, by polyclonal and monoclonal antibodies against beta 1-containing
      integrins. These results provide evidence that TAG-1 can interact with cell
      surfaces in both a homophilic and heterophilic manner and suggest that neurite
      extension on TAG-1 requires the function of both integrins and an L1-like
      molecule.

PMID- 7512356
TI  - A study of dose escalation of teniposide (VM-26) plus cisplatin (CDDP) with
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients
      with advanced small cell lung cancer.
AB  - A dose escalation study of teniposide (VM-26) plus cisplatin (CDDP) was carried
      out using recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 46
      previously untreated patients with advanced small cell lung cancer (SCLC). The
      dose of CDDP was 80 mg/m2/day intravenously (i.v.) (day 1) and VM-26 was
      escalated from 60 mg/m2/day to 80, 100 and 120 mg/m2/day i.v. x 5 days for four
      cycles. The dose of rhG-CSF was 90 micrograms/m2/day subcutaneously for 13 days.
      The feasibility of the regimen at the starting dose level of VM-26 with or
      without rhG-CSF was initially examined in 10 patients chosen through random
      allocation. WHO grade 4 neutropenia was observed in 17% (three out of 18 courses)
      of patients in the rhG-CSF group and in 63% (12 out of 19 courses) of the control
      group (P < 0.01). The number of patients with febrile episodes (> 38 degrees C)
      over the four courses of chemotherapy was 1 in the rhG-CSF group and 4 in the
      control group. According to these results, all 36 patients received rhG-CSF in
      the dose escalation stage. The incidence of WHO grade 4 neutropenia at the dose
      levels of 60, 80, 100 and 120 mg/m2/day of VM-26 was 66, 57, 76 and 85%,
      respectively (P > 0.1). The incidence of grade 4 thrombocytopenia was 19, 31, 18
      and 46%, respectively (P > 0.1). The overall response rate was 100% in patients
      with limited stage SCLC and 83% in patients with extensive stage SCLC. The actual
      administered VM-26 dose per week at the dose level of 100 mg/m2/day was 1.6-fold
      higher than the planned starting dose (60 mg/m2/day) per week. At the dose level
      of 120 mg/m2/day, 50% of patients developed WHO grade 4 leucopenia, which lasted
      longer than 1 week and 67% of the patients had WHO grade 3 or 4 diarrhoea. At
      this same dose, all patients had at least one febrile episode (> 38 degrees C),
      and 1 patient died of cerebral bleeding with severe thrombocytopenia. The median
      survival time of all patients was 451 days (411 days, extensive disease; 497
      days, limited disease). VM-26 plus CDDP with rhG-CSF was active in previously
      untreated patients with SCLC. The recommended dose of VM-26 in combination with
      CDDP for a phase II study is 100 mg/m2/day for 5 days with rhG-CSF support.

PMID- 7512357
TI  - Does improved control of tumour growth require an anti-cancer therapy targeting
      both neoplastic and intratumoral endothelial cells?

PMID- 7512359
TI  - Education in cancer palliative care. Report from a consensus meeting supported by
      the EC "Europe Against Cancer" programme.

PMID- 7512358
TI  - Clinical utilisation of human haematopoietic progenitors elicited in peripheral
      blood by recombinant human granulocyte colony-stimulating factor (rHuG-CSF).

PMID- 7512360
TI  - Evaluation of the role of second messenger systems in tumor necrosis factor
      stimulated resorption of fetal rat limb bones.
AB  - Tumor necrosis factor (TNF) actions in target tissues are mediated by various
      signalling pathways. The effect of TNF to stimulate resorption in fetal rat limb
      bones is not inhibited by indomethacin. The current studies were designed to
      assess the role of cyclic AMP (cAMP) and calcium as second messengers in this
      prostaglandin-independent action of TNF on bone resorption. TNF alone failed to
      increase cyclic AMP in fetal rat limb bones after either brief (15 min) or long
      term (72 h) treatment. TNF-stimulated resorption in fetal rat limb bones was
      enhanced by the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX). In
      short term incubations, the combination of TNF + IBMX did not elicit increases in
      cAMP in the limb bones. In 72 h cultures, addition of IBMX revealed a dose
      dependent effect of TNF to increase cAMP. TNF produced a significant increase in
      inositol phosphate turnover in limb bones, with a greater response at 5 min than
      at 1 or 20 min. The calcium channel blocker nitrendipine inhibited TNF-stimulated
      resorption in the fetal rat limb bones. TNF-stimulated resorption was attenuated
      by pretreatment with pertussis toxin (PTx). PTx did not inhibit the effect of TNF
      to increase inositol phosphate turnover. TNF did not increase cAMP, intracellular
      calcium, or inositol phosphates in the UMR-106 cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7512361
TI  - Telling young children with leukemia their diagnosis: the flower garden as
      analogy.
AB  - A new approach to communicating the diagnosis of leukemia to the young child was
      carried out in the Pediatric Hematology Department in Monza over a 2-year period
      (1989 to 1991). Fifty patients ages 6 to 15 years were entered into the program.
      A physician communicated the diagnosis of leukemia directly to the child without
      the presence of the parents. A set of 25 slides was prepared. A garden with
      flowers and weeds was used as an analogy for leukemia. All 50 of the children
      expressed gratitude for understanding their disease and the families for being
      able to talk with their children about the disease without panic and stress.

PMID- 7512362
TI  - Growth and survival in small hepatocellular carcinoma.

PMID- 7512363
TI  - Cytogenetic deletion maps of hematologic neoplasms: circumstantial evidence for
      tumor suppressor loci.
AB  - Research in oncogenetics has led to the identification of two major classes of
      tumor-associated genes, oncogenes and tumor suppressor genes. In a wide variety
      of solid tumor types, mutations of both groups of genes have been implicated in
      the tumorigenic process. In hematologic neoplasms, on the other hand, most
      attention has focused on illegitimate activation of oncogenes, e.g., deregulation
      leading to disturbed transcriptional activity and structural rearrangements
      resulting in hybrid genes. Whether loss or mutational inactivation of tumor
      suppressor genes also plays an essential role in the genesis of tumors of the
      hematopoietic system has received less attention. Because such inactivation can
      be the result of karyotypically detectable loss of chromosomal material,
      cytogenetic studies may prove helpful in pinpointing genomic sites that harbor
      tumor suppressor genes. The present study is based on a total of 12,473
      cytogenetically abnormal hematologic neoplasms reported in the literature to
      date. Among these, we selected the 6,422 cases with sole clonal chromosomal
      abnormalities in order to include only aberrations of importance in the genesis,
      rather than in the progression, of these neoplasms. All tumors with monosomies or
      structural abnormalities resulting in loss of chromosomal material were compiled,
      and for every such structural aberration, i.e., deletion, unbalanced
      translocation, isochromosome, and ring chromosome, the chromosome bands lost were
      ascertained. This cytogenetic deletion mapping revealed that the most commonly
      lost chromosomes were Y and 7 in acute myeloid leukemia (AML), myelodysplastic
      syndromes (MDS), and chronic myeloproliferative disorders (MPD); X, Y, 7, 20, and
      21 in acute lymphocytic leukemia (ALL); X, Y, and 17 in chronic
      lymphoproliferative disorders (LPD); and X and Y in non-Hodgkin's lymphoma (NHL).
      Chromosome segments/bands lost due to unbalanced structural abnormalities in at
      least 5% of the cases were 5q13-33, 7q22-36, 9q13-31, 11q23-25, 12p12-13, 17p11
      13, and 20q11-13 in AML; 5q13-35 and 20q11-13 in MDS; 5q22-23, 7q22, 13q12-22,
      17p11-13, and 20q11-13 in MPD; 6q15-27, 9p11-24, 12p12-13, and 19p13 in ALL; 6q16
      27, 11q21-25, 13q13-14, and 14q32 in LPD; and 6q21-27, 11q13-25, and 14q24-32 in
      NHL. Based on these findings, three conclusions can be drawn. First, there is no
      good correspondence between total and partial monosomies, the only exception
      being -7 and 7q-, both of which are common in myeloid neoplasms. This indicates
      different pathogenetic effects of total and partial losses.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7512364
TI  - Power of the MAC (morphology-antibody-chromosomes) method in distinguishing
      reactive and clonal cells: report of a patient with acute lymphatic leukemia,
      eosinophilia, and t(5;14).
AB  - We present a patient with acute lymphatic leukemia, eosinophilia, and a 5;14
      translocation, a rare but well-documented condition. In order to clarify whether
      granulocytes were involved in the disease, we applied the MAC (Morphology
      Antibody-Chromosomes) technique to samples of the bone marrow and, during a
      central nervous system relapse, to those of the cerebrospinal fluid. The
      karyotype of the blast cells was 47,XY, + X,t(5;14)(q31;q32),i(7)(q10).
      Interphase cytogenetic study by in situ hybridization with an X-specific alphoid
      probe revealed the abnormality in CD10, CD19, and TdT (terminal deoxynucleotidyl
      transferase) positive lymphoid cells, whereas CD13 positive, Sudan black B
      positive, eosinophilic, and basophilic granulocytes as well as monocytes and
      small lymphocytes did not have the abnormality. Our results show that the
      eosinophilic and basophilic granulocytes in this subtype of acute leukemia do not
      belong to the malignant clone but are reactive. This study also confirmed the
      usefulness of the MAC technique in distinguishing neoplastic and reactive cells
      in malignancy.

PMID- 7512365
TI  - Molecular mapping of the chromosome 11 breakpoint of t(11;17)(q13;q21) in a
      t(11;14)(q13;q32)-positive B non-Hodgkin's lymphoma.
AB  - The FAU gene is the cellular homologue of the viral FOX sequences in the genome
      of the Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV); the viral FOX
      sequences have been shown to increase the transforming capacity of FBR-MuSV in
      vitro. The human FAU gene has recently been isolated, characterized, and mapped
      to chromosome band 11q13. Here, we report results of fluorescence in situ
      hybridization (FISH) analysis which indicate that the FAU gene maps proximally to
      the putative oncogene BCL1 at 11q13. Furthermore, we identified a
      t(11;17)(q13;q21) translocation in tumor cells of a t(11;14)(q13;q32)-positive B
      cell non-Hodgkin's lymphoma patient by FISH analysis using a FAU containing
      cosmid clone as molecular probe and by double-colour chromosome painting analysis
      using chromosome 11- and chromosome 17-specific painting probes. The position of
      the chromosome 11 breakpoint of the t(11;17) translocation was pinpointed to a
      human DNA region around the FAU gene of about 40 kbp.

PMID- 7512366
TI  - Molecular cytogenetic analysis of i(12p)-negative human male germ cell tumors.
AB  - The i(12p) chromosome has been shown to characterize more than 80% of male germ
      cell tumors (GCTs) and is an important diagnostic marker. Although recent
      cytogenetic analyses of GCTs have defined nonrandom chromosome abnormalities in
      these tumors, no attempt has so far been made to compare i(12p)-positive and 
      negative tumors in terms of their cytogenetic, histologic, and clinical features.
      During a 5-year period, we have ascertained 202 GCTs, of which 117 had clonally
      abnormal karyotypes. Among the latter, 91 had one or more copies of i(12p),
      whereas 26 lacked an i(12p). We report here the karyotypic analysis of these 26
      i(12p)-negative GCTs. In this group, nonrandom sites of chromosomal
      rearrangements included 12p13 (9/26) and 1p11-q11 (5/26). Comparison of the
      cytogenetic features of i(12p)-negative tumors with i(12p)-positive tumors
      revealed the only significant difference to be rearrangements affecting 12p13 in
      the former (35%) as compared to their absence in the latter (3%). Hybridization
      of metaphase preparations of 9 i(12p)-negative tumors with a chromosome 12
      painting probe and with a microdissected 12p painting probe revealed extra copies
      of chromosome 12 segments incorporated into marker chromosomes whose composition
      could not otherwise be resolved by banding analysis; all were shown to be derived
      from 12p. These data demonstrate that both i(12p)-negative and -positive groups
      are characterized by an increased copy number of 12p, which is consistent with a
      lack of significant clinical or biological difference between them. An increased
      12p copy number thus is a specific aberration of significance to the development
      of germ cell tumors.

PMID- 7512367
TI  - Translocation of BCR to chromosome 9: a new cytogenetic variant detected by FISH
      in two Ph-negative, BCR-positive patients with chronic myeloid leukemia.
AB  - Leukemic cells from two patients with Philadelphia-negative chronic myeloid
      leukemia (CML) were investigated: 1) Cytogenetics showed a normal 46,XY karyotype
      in both cases, 2) molecular studies revealed rearrangement of the M-BCR region
      and formation of BCR-ABL fusion mRNA with b2a2 (patient 1) or b3a2 (patient 2)
      configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated
      relocation of the 5' BCR sequences from one chromosome 22 to one chromosome 9.
      The ABL probe hybridized to both chromosomes 9 at band q34, while two other
      probes which map centromeric and telomeric of BCR on 22q11 hybridized solely with
      chromosome 22. For the first time, a BCR-ABL rearrangement is shown to take place
      on 9q34 instead of in the usual location on 22q11. A rearrangement in the latter
      site is found in all Ph-positive CML and in almost all investigated CML with
      variant Ph or Ph-negative, BCR-positive cases. The few aberrant chromosomal
      localizations of BCR-ABL recombinant genes found previously were apparently the
      result of complex and successive changes. Furthermore in patient 2, both
      chromosomes 9 showed positive FISH signals with both ABL and BCR probes.
      Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic
      recombination had occurred on the long arm of chromosome 9 and that the
      rearranged chromosome 9 was of paternal origin. The leukemic cells of this
      patient showed a duplication of the BCR-ABL gene, analogous to duplication of the
      Ph chromosome in classic CML. In addition they had lost the maternal alleles of
      the 9q34 chromosomal region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512368
TI  - Analysis of deletions of the long arm of chromosome 11 in hematologic
      malignancies with fluorescence in situ hybridization.
AB  - We studied samples containing deletions of the long arm of chromosome 11 (11q)
      from patients with hematologic malignancies by using cytogenetic and fluorescence
      in situ hybridization (FISH) techniques. Cytogenetic analysis of 28 patients and
      of a cell line showed that all deletions included band 11q23. FISH analysis
      demonstrated that the proximal part of 11q23, including NCAM, was deleted in 13
      of 15 patients and the cell line. Recurring chromosomal losses in human tumors
      have been regarded as evidence that the affected regions contain tumor-suppressor
      genes. These results suggest that the putative tumor-suppressor gene is proximal
      to the MLL gene which is also located in 11q23.

PMID- 7512369
TI  - Identification of a novel protein with GDP dissociation inhibitor activity for
      the ras-like proteins CDC42Hs and rac I.
AB  - We have recently cloned the human cDNA for a gene, denoted D4, that encodes a
      protein 67% identical to the bovine rhoGDI protein, a GDP dissociation inhibitor
      (GDI) for the ras-related rho-subtype proteins. We now present data on the
      cloning and structural analysis of the murine D4 cDNA and confirm its
      preferential expression in hematopoietic tissues. The predicted murine and human
      D4 proteins are almost 90% identical, indicating that D4 and rhoGDI are different
      genes and that they are probably members of a related family of genes. Functional
      studies with the human D4 protein demonstrate that D4 has GDI activity against
      the CDC42Hs and rac I proteins, but binds to these proteins with a significantly
      weaker affinity than does the rho-subtype GDI. These data suggest that D4, which
      will in subsequent communications be denoted as GDI.D4, might be a GDI for other
      known or as yet unidentified ras-like GTP-binding proteins. Alternatively, D4
      could have other biochemical functions. During murine embryogenesis, D4
      transcripts are detected in yolk-sac cells, where the earliest hematopoietic
      precursors are found. When these precursors undergo proliferation and
      differentiation in vitro, a dramatic increase in D4 expression is seen. D4
      probably has a significant function during the growth and development of
      hematopoietic precursors.

PMID- 7512370
TI  - Chromosome abnormalities in non-small cell lung cancer pleural effusions:
      cytogenetic indicators of disease subgroups.
AB  - A cytogenetic study of pleural effusions (PE) containing metastatic or invasive
      tumor cells from 11 patients with non-small cell lung cancer (NSCLC) (3 squamous
      cell carcinomas [SQC] and 8 adenocarcinomas [ADC] including 1 giant cell variant)
      was performed to identify non-random chromosome abnormalities. Numerical
      abnormalities seen in > or = 30% of cases included gain of chromosomes 7 and 20,
      and loss of chromosomes 4, 9, 10, 13, 15, 16, 18, 19, 21, and 22. The most
      frequent structural abnormality involved rearrangement in 1p with breakpoints
      clustering at 1p10-p13. Other recurrent breakpoint regions, seen in > or = 30% of
      cases, occurred in chromosome region 3p10-p21, 3q11-q25, 6p11-p25, 6q13-q23, 7q11
      q36, 9q32-q34, 11p11-p13, 11q13-q24, 13p/14p and/or 15p, 17p and 19p, with, in
      particular, apparent loss of 6q21-q27, 3p21-p26, 7q21-q22, 9p22-p24 (shortest
      regions of common overlap) and 17p. There was also recurrent gain of 1q23-q44,
      8q13-q24, and 11q13-q23. These abnormalities were not restricted to a particular
      histological subtype, with the exception of +8 and a breakpoint in 9q32-q34,
      which were seen only in ADC. The 9q32-q34 breakpoint observed in 4 ADC PE
      (including 1 giant cell variant) represents a new observation in NSCLC. These
      findings, when compared to those reported for primary NSCLC indicate cytogenetic
      differences between the two which may be associated with pleural invasion of
      NSCLC.

PMID- 7512371
TI  - Unusual deletions in the immunoglobulin heavy chain locus in follicular B-cell
      lymphoma with t(14;18)(q32.3;q21.3).

PMID- 7512372
TI  - Palmitoylation of CD44 interferes with CD3-mediated signaling in human T
      lymphocytes.
AB  - We studied the interactions between CD44 and four different monoclonal anti-CD44
      antibodies. All four monoclonal anti-CD44 antibodies studied (P3H9, Bu52, IM.7,
      and GKW.A3) act in synergy with human anti-CD2 antibodies in stimulating normal
      human peripheral blood lymphocytes to proliferate. GKW.A3 and IM.7 but not P3H9
      or Bu52 inhibited the proliferation of normal human peripheral blood lymphocytes
      stimulated by anti-CD3. Interestingly, only GKW.A3 and IM.7 stimulated the
      incorporation of [3H]palmitic acid and palmitoylation of CD44 molecules by normal
      human peripheral blood lymphocytes. The two monoclonal anti-CD44 antibodies (P3H9
      and Bu52) that failed to inhibit anti-CD3 induced proliferation also failed to
      induce the incorporation of [3H]palmitic acid. More importantly, the inhibitory
      effects of GKW.A3 were reversed in the presence of cerulenin, an inhibitor of
      protein palmitoylation. Therefore, palmitoylation of CD44 may interfere with anti
      CD3 mediated signaling pathways. These data support the hypothesis that
      palmitoylation of cell surface receptors may play an active role in receptor and
      receptor interactions and signal transduction in normal human T lymphocytes.

PMID- 7512373
TI  - Distinct binding specificities of integrins alpha 4 beta 7 (LPAM-1), alpha 4 beta
      1 (VLA-4), and alpha IEL beta 7.
AB  - Integrin receptors are important for regulating lymphocyte recirculation and
      recruitment to sites of inflammation. Transfectants of the B cell lymphoma 38C13
      were generated that differ exclusively in the expression of integrin beta 1 or
      beta 7 subunits allowing for a functional comparison of lymphocyte Peyer's patch
      HEV adhesion molecule 1 (LPAM-1) (alpha 4 beta 7) and very late antigen 4 (VLA-4)
      (alpha 4 beta 1) in an identical cellular environment. Whereas 38-beta 7
      transfectants bound to purified and cellular mucosal addressin cell adhesion
      molecule (MAdCAM-1), unstimulated 38-beta 1 cells failed to bind MAdCAM-1.
      Treatment of 38-beta 1 cells with Mn2+ but not with PMA induced low level binding
      to MAdCAM-1. MAdCAM-1 adhesion of 38-beta 7 cells was constitutive and not
      enhanced by Mn2+ treatment. Similarly, MAdCAM-1-dependent adhesion to mucosal
      high endothelial venules was shown for 38-beta 7 but not for 38-beta 1 cells. The
      results therefore establish the LPAM-1-MAdCAM-1 interaction as the functionally
      dominant adhesion pathway for regulating lymphocyte homing to mucosal sites.
      Nonetheless, the activated VLA-4 on some lymphocytes may be involved in MAdCAM-1
      recognition or promote binding to MAdCAM-1 in other tissues. By contrast, 38-beta
      7 and 38-beta 1 transfectants did not differ in their binding capacity for
      vascular cell adhesion molecule 1 (VCAM-1) or fibronectin and LPAM-1 did not
      display any preference for interacting with either MAdCAM-1 or VCAM-1. LPAM-1 may
      therefore contribute significantly to cellular functions previously attributed to
      VLA-4. Interestingly, functional analysis of the intraepithelial lymphocyte
      integrin alpha IEL beta 7 which is structurally related to LPAM-1 did not reveal
      detectable binding activity for MAdCAM-1, VCAM-1, or fibronectin.

PMID- 7512374
TI  - Induction of tolerance to self MHC class I molecules expressed under the control
      of milk protein or beta-globin gene promoters.
AB  - We have studied tolerance induction in transgenic CBA mice expressing H-2Kb genes
      under the influence of guinea-pig alpha-lactalbumin (KAL) or human beta-globin
      gene promoter (K beta). KAL radio-resistant cells, but not bone marrow derived
      cells, induce tolerance to H-2Kb in chimeric mice. In contrast, bone marrow
      derived and radio-resistant cells of K beta mice induce tolerance. Although
      appropriate, tissue-specific, expression of H-2Kb molecules occurs in KAL and K
      beta mice, H-2Kb is expressed at low levels in thymus of transgenic mice. In
      addition, dendritic cells and macrophages express H-2Kb molecules when K beta,
      but not when KAL bone marrow is cultured in vitro. The mode of tolerance
      induction was examined in double transgenic mice by mating KAL or K beta mice to
      mice expressing TCR transgenes (Tg-TCR) derived from a H-2Kb specific, CD8
      independent cytotoxic T cell clone. In both cases, a large number of Tg-TCR+
      CD8+CD4+ thymocytes develop but mature CD8+CD4- thymocytes fail to appear
      suggesting that thymocytes are eliminated late in development. Some CD8-CD4- and
      CD8-CD4+ Tg-TCR+ T cells develop in double transgenic mice and respond to
      activation through their TCR-CD3 complex in vitro, although no responses to
      stimulation with H-2Kb expressing cells were detected. Thus, tolerance induction
      in KAL and K beta mice proceeds via a deletional mechanism that is inefficient
      due either to low numbers of H-2Kb expressing thymic cells or to the low levels
      of H-2Kb expressed by thymic cells, or to a combination of these factors.

PMID- 7512375
TI  - Limitations of predictive motifs revealed by cytotoxic T lymphocyte epitope
      mapping of the human papilloma virus E7 protein.
AB  - Human papilloma virus (HPV) type 16 is found in the majority of cervical cancer
      patients and the transforming protein E7 is consistently expressed in cancer
      cells, making it a potential target for immune attack. In this study we have
      investigated whether E7 gains access to the MHC class I processing pathway and
      provides cytotoxic T lymphocyte (CTL) stimulating peptide epitopes. CTL were
      induced in H-2b mice by immunization with recombinant vaccinia virus expressing
      E7 (Vac-E7). To map CTL recognition, natural peptides were purified from cells
      expressing either intact or truncated E7 protein. Following peptide separation by
      HPLC one major CTL epitope was detected and truncated constructs localized this
      epitope to the C-terminal region. Mapping with synthetic peptides indicated that
      residues 49-57 (RAHYNIVTF) were recognised by anti-E7 CTL. Synthetic 49-57
      peptide was used to induce CTL, which recognized the same HPLC purified natural
      peptide fractions as anti-E7 CTL. Binding motifs for H-2b class I molecules did
      not predict residues 49-57 to be a CTL epitope, but instead the sequence 21-28
      (DLYCYEQL) which contains a Kb anchor motif. Synthetic 21-28 peptide was found to
      bind to Kb class I molecules and readily induced CTL, indicating that the T cell
      repertoire of H-2b mice can recognize this epitope. However, these CTL did not
      recognize peptides isolated from E7 expressing cells, showing that natural
      processing did not produce detectable levels of the 21-28 epitope. Together, the
      data demonstrate that an unexpected E7 peptide can function as a major CTL
      epitope.

PMID- 7512376
TI  - Substitution of class II alpha chain polymorphic residues defines location of A
      alpha k serologic epitopes and alters association between alpha beta and Ii
      polypeptides.
AB  - Structure-function studies of the MHC class II alpha chain have been performed by
      constructing a panel of A alpha k cDNA genes with one or more d allele
      substitutions at each polymorphic residue of the alpha 1 domain. The altered
      genes (A alpha k*) were transfected into a B lymphoma cell line (BKO), which is
      deficient in A alpha mRNA but retains constitutive wild-type A beta k mRNA
      expression. Cytofluorometric analysis of cell surface A alpha k* Ak beta
      molecules was used to map the polymorphic alpha chain residues comprising four
      serologic epitopes. A alpha k-reactive mAbs 1E9, 2A2, and 3F12 recognize an
      epitope that includes the polymorphic residue 44 of the A alpha k polypeptide,
      and the A alpha k-reactive antibody, K24-199, recognizes a conformationally
      determined epitope influenced by residues from all three polymorphic regions. In
      addition, we confirmed previous studies demonstrating that la.19 and la.2 mAbs
      bind to epitopes adjacent to residue 75 in A alpha k. A cell surface negative
      expression variant also was identified in the panel of mutant cell lines and
      biochemically characterized. Substitution of six d allele polymorphic residues at
      positions 11, 14, 28, 69, 70, and 75 in the A alpha k polypeptide (T.EG A alpha
      k* A beta k*) results in an A alpha k* polypeptide that associates with the A
      alpha k polypeptide but does not associate with the li polypeptide. This defect
      in li-A alpha k A beta k interaction is associated with a conformational change
      in the alpha 1 beta 1 domain that was identified by altered reactivity of the
      T.EG complex with conformationally dependent anti-alpha and anti-beta
      mAbs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512378
TI  - [Hemorrhagic glaucoma].
AB  - The hemorrhagic glaucoma defines a clinical syndrome which recognizes as a
      frequent symptoms the hemorrhagic element, and from the morphopathological point
      of view the presence of some neoformation vessels at the level of the iris and
      camerular angle. 22 clinical observations of hemorrhagic glaucoma which appeared
      during one year are analyzed. It is shown that the new vessels appear as a
      reaction of the tissues hypoxemia and especially to alon of the oxygen pressure
      that determines the increase of the vessels. Also in the hemorrhagic glaucoma
      appears a deficiency of the venous reaction which determines a deficiency of the
      venous flow. The new vessels appear because of the hypoxemia and acid lactic
      accumulation only as the presence of a vital iridian tissue, because the new
      vessels do not appear in necrotic tissues.

PMID- 7512377
TI  - Attachment of human bone cells to tissue culture polystyrene and to unmodified
      polystyrene: the effect of surface chemistry upon initial cell attachment.
AB  - Cell culture studies have often been used in the determination of the suitability
      of biomaterials as surfaces for the attachment and growth of cells. For such
      studies of surfaces for potential use in bone implants, cells derived from bone
      may be maintained in culture on tissue culture polystyrene (TCPS). We have
      determined the contribution that serum fibronectin (FN) or vitronectin (VN) make
      to the attachment and spreading of cells cultured from explanted human bone (bone
      derived cells) during the first 90 min following seeding on culture surfaces. The
      attachment of bone-derived cells to TCPS was simulated two-fold by the addition
      of 10% (v/v) fetal bovine serum (FBS) to the seeding culture medium. The roles of
      FN and VN were determined by selective removal of the FN or VN from the FBS prior
      to addition to the culture medium. FBS from which the VN had been removed did not
      have this stimulatory activity. In contrast, the attachment of bone-derived cells
      onto TCPS from medium containing FN-depleted serum (which contained VN) was the
      same as when intact FBS was used. There was incomplete attachment of bone-derived
      cells (27% of cells) when seeded in medium containing FBS depleted of both VN and
      FN. Our results show that for human bone-derived cells, the attachment onto TCPS
      of cells planted in medium containing FBS during the first 90 min of culture is
      principally as a result of adsorption onto the surface of serum VN. As unmodified
      polystyrene (PS) has also been used previously as a model biomaterial surface, PS
      was compared to TCPS for attachment of the bone-derived cells. Attachment of bone
      derived cells to TCPS was twice that onto PS, both when the medium was serum-free
      and when it contained FBS. Bone-derived cells attached to TCPS or PS onto which
      purified VN or FN had been precoated, with VN adsorbed onto PS being as effective
      as was VN adsorbed onto TCPS. With FN, there was an effect of the polystyrene
      surface chemistry which was evident in that suboptimal concentrations of FN had a
      slightly higher potency when adsorbed onto TCPS than did the same concentrations
      of FN coated onto PS. When preadsorbed onto TCPS, the potency of FN for
      attachment of bone-derived cells was at least equal to that of VN.

PMID- 7512380
TI  - Acylation of myelin basic protein peptide 1-21 with alkyl carboxylates 2-10
      carbons long affects secondary structure and posttranslational modification.
AB  - A peptide consisting of the first 21 residues of human myelin basic protein (MBP)
      was synthesized. The N-terminal alanine of portions was blocked in separate
      experiments with alkyl carboxylates varying in size from 2 to 10 carbon atoms.
      The effects of these different alkyl carboxylates at the N-terminus on the
      secondary structure was studied by circular dichroism (250-190 nm). In water, the
      spectra of the unblocked peptide suggested unordered structure with large
      negative ellipticities at 198 nm. Addition of an acetyl group altered the
      magnitude of [theta]198 from -21856 +/- 2319 to -11095 +/- 1000 deg cm2 dmol-1,
      suggesting a significant increase in ordered structure. When peptides with longer
      alkyl carboxylates, acylated at the N-termini, were studied, the magnitude of
      theta 198 approached that of the unblocked peptide but greater negative
      ellipticities were observed for the C8 and C10 alkyl carboxylates. The theta 222
      values were generally low (-1803 +/- 463) but increased with increasing length of
      the alkyl carboxylate to about -3200 deg cm2 dmol-1, suggesting that little alpha
      helical structure was present. The spectra were also taken in lipid-mimetic
      solvents, including 2-propanol, methanol, and lysophosphatidylglycerol (lysoPG).
      In general the theta 198 and theta 222 values were suggestive of increased
      structure in these environments compared to water. In 90% 2-propanol the theta
      198 of the unblocked peptide did not change when an acetyl group was added to the
      N-terminus (9088 compared to 8477 deg cm2 dmol-1). Addition of longer alkyl
      carboxylates correlated with larger, negative ellipticities.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7512381
TI  - Gramicidin A/short-chain phospholipid dispersions: chain length dependence of
      gramicidin conformation and lipid organization.
AB  - Gramicidin-lipid interactions were investigated using diacylphosphatidylcholines
      that contained two identical acyl chains of varying length, between 6 and 14
      carbons. The gramicidin A (gA) conformation was monitored by circular dichroism
      (CD) spectroscopy and high-performance size-exclusion chromatography, and the
      lipid organization was investigated using 31P and 1H NMR spectroscopy and
      negative-stain electron microscopy. Diacylphosphatidylcholine (PC) lipids with
      chain lengths between 4 and 8 carbons have been previously shown to have a
      micellar organization in aqueous solution [Lin, T.-L., et al. (1986) J. Am. Chem.
      Soc. 108, 3499-3507]. CD spectra of aqueous gA/lipid dispersions, at a ratio of
      1:28, demonstrated that the channel conformation of gA can be readily obtained
      when the acyl chain length is > or = 10, but not when the chain length is < or =
      7. Size-exclusion chromatography revealed that the fraction of gA that could
      easily be dissociated into monomers in the dispersions increased with increasing
      acyl chain length, in agreement with the CD results. For a chain length of 8, the
      results were intermediate. The formation of the channel structure was found to
      depend on the "solvent-history", the temperature, the gA and lipid
      concentrations, the gA:lipid ratio, and consequently on the method of sample
      preparation. 1H and 31P NMR results suggest that codispersed gA increases the
      size of dioctanoyl-PC aggregates, but not of dihexanoyl-PC micelles. Negative
      stain electron microscopy directly supports these findings. Dihexanoyl-PC (28 mM)
      was able to solubilize 1 mM gA in H2O, but the gA was not in the "channel"
      conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512382
TI  - Conformational change in antithrombin induced by heparin probed with a monoclonal
      antibody against the 1C/4B region.
AB  - A murine monoclonal antibody (MAb) raised against a covalent antithrombin-heparin
      complex was used to probe the conformational change resulting when the serpin
      antithrombin binds to heparin. This MAb completely inhibited the progressive
      activity of antithrombin against thrombin. However, although the MAb remained
      bound to antithrombin in the presence of heparin, it did not significantly
      inhibit heparin cofactor activity against thrombin, and increasing concentrations
      of the antithrombin-binding pentasaccharide progressively unblocked the
      inhibitory action of the MAb. The MAb bound to antithrombin without affecting
      either heparin-binding affinity or heparin-induced fluorescence enhancement, and
      it did not convert antithrombin from inhibitor to substrate. The MAb failed to
      interact with reduced and S-carboxymethylated antithrombin, indicating the
      conformational nature of its epitope. Antithrombin variants with N-terminal
      substitutions (Arg47-->Cys or His, Leu99-->Phe, Arg129-->Gln) modifying heparin
      binding, and C-terminal substitutions affecting the reactive site (Arg393-->Cys)
      or resulting in substrate-variant antithrombin (Ala384-->Pro), were all
      recognized normally, as were normal reactive site cleaved antithrombin and the
      thrombin-antithrombin complex. However, interaction of the MAb with antithrombin
      was reduced by several substitution mutations (Phe402-->Cys, Phe402-->Ser, Phe402
      ->Leu, Ala404-->Thr, Pro407-->Thr) in the 402-407 sequence which codes for amino
      acid residues of strand 1C and the polypeptide leading to strand 4B. Pro429-->Leu
      also blocks recognition [Olds et al. (1992) Blood 79, 1206-1212], and this
      residue is believed to be spatially approximated to strand 1C.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7512379
TI  - 15N NMR relaxation studies of the FK506 binding protein: dynamic effects of
      ligand binding and implications for calcineurin recognition.
AB  - Backbone dynamics of the ligand- (FK506-) bound protein FKBP-12 (107 amino acids)
      have been examined using 15N relaxation data derived from inverse-detected two
      dimensional 1H-15N NMR spectra. A model free formalism [Lipari & Szabo (1982) J.
      Am. Chem. Soc. 104, 4546-4559] was used to derive the generalized order parameter
      (S2), the effective correlation time for internal motions (tau e), and the
      chemical-exchange line width (R(ex)) based on the measured 15N relaxation rate
      constants (R1, R2) and 1H-15N heteronuclear NOEs. The final optimized overall
      correlation time (tau m) was 9.0 ns. The average order parameter (S2) describing
      the amplitude of motions on the picosecond time scale was found to be 0.88 +/-
      0.04, indicating that internal flexibility is restricted along the entire
      polypeptide chain. In contrast to results obtained for uncomplexed FKBP, the 80's
      loop (residues 82-87) surrounding the ligand binding site was found to be rigidly
      fixed, indicating that internal motions at this site are damped significantly due
      to stabilizing noncovalent interactions with the FK506 molecule. Structural
      implications of these differences in picosecond mobility as well as possible
      implications for calcineurin recognition are discussed.

PMID- 7512383
TI  - Two mode ion channels induced by interaction of acidic amphipathic alpha-helical
      peptides with lipid bilayers.
AB  - In order to investigate the ion permeability and selectivity of ion channel
      formed by amphipathic alpha-helical peptides, we designed to synthesize an acidic
      peptide Ac(Leu-Ala-Glu-Leu)3NHCH3 (Glu-4(3)) and its channel property was
      compared with a basic peptides Arg-4(3) in which Glu in Glu-4(3) was replaced by
      Arg. Two modes of the conductance change were observed by the interaction of Glu
      4(3) with planar lipid bilayers; a steady increase of the conductance with the
      elapse of time (mode 1) and a spike-like increase of the current (mode 2)
      appearing with a lag time and overlapping the model current increase. The
      application of negative membrane potential induced the mode 1 current and the
      lowering pH decreased it, suggesting that the mode 1 current is caused by slow
      insertion of Glu-4(3) into the lipid bilayer and then by forming certain unknown
      bundles like semichannels. Mode 2 was found to be consisted of channel type
      opened-close current with several different conductances and relatively short
      opening lifetimes. There was no ion selectivity in the mode 1 current, whereas
      the mode 2 current was cation selective. The peptide Arg-4(3) has formed a cation
      selective ion channel but not shown such two mode current changes. The membrane
      potential formation experiment in liposomes using DiSC3(5) also showed the cation
      selectivity for Arg-4(3) and non-ion selectivity for Glu-4(3). The difference
      between Arg-4(3) and Glu-4(3) was also observed in conformational analysis by CD
      and in dye-release experiment from liposome. Such difference was discussed in
      terms of electrostatic interaction between peptides and lipid head groups.

PMID- 7512384
TI  - Lipid modulation of nicotinic acetylcholine receptor function: the role of
      membrane lipid composition and fluidity.
AB  - The effects of membrane lipid composition and fluidity on AChR ion channel
      function were studied after reconstituting the receptor with sphingomyelin,
      phosphatidylcholines with different degrees of unsaturation, or different neutral
      lipids. AChR ion flux activity was shown to be retained in some membranes of both
      high and low fluidity, as measured by the steady-state anisotropy of the membrane
      probes diphenylhexatriene and trimethylammonium diphenylhexatriene. The results
      suggest that lipid composition is more important than bulk membrane fluidity in
      determining AChR ion channel function.

PMID- 7512386
TI  - Role of PI 3-kinase in mitogenesis.

PMID- 7512385
TI  - Monoclonal antibodies against human thrombomodulin whose epitope is located in
      epidermal growth factor-like domains.
AB  - Thrombomodulin (TM) on endothelial cells is a glycoprotein that functions as a
      cofactor for thrombin-catalyzed activation of protein C. The structural
      requirement for thrombin binding and cofactor activity were investigated using
      monoclonal antibodies (moAbs) against TM and site-directed mutagenesis of
      recombinant human soluble TM (rsTM). Results showed that moAb 2A2 inhibited
      thrombin binding to rsTM and also abolished its functions as a cofactor in
      thrombin-catalyzed activation of protein C and as an anticoagulant by modifying
      thrombin-induced fibrinogen clotting and platelet aggregation, moAb 1F2 did not
      affect its activity as an anticoagulant, but inhibited its cofactor activity, and
      moAb 10A3 did not inhibit either activity. Epitope analysis was carried out by
      site directed mutagenesis of rsTM expressed in CHO cells. Some proteins with
      mutations within the second disulfide loop of the fourth EGF-like domain showed
      reduced affinity for moAb 1F2, but retained cofactor activity. These results
      suggest that the epitope of moAb 1F2 includes the second disulfide loop of the
      fourth EGF-like domain, which is close to a region required for cofactor
      activity. Mutant proteins of the third disulfide loop of the fifth EGF-like
      domain showed loss of interaction with moAb 2A2. Thus the epitope of moAb 2A2 may
      include the third disulfide loop of the fifth EGF-like domain. Furthermore,
      replacement of Asn-439 by Gln decreased the cofactor activity and anticoagulant
      activity, and resulted in low affinity for either moAb 1F2 or 2A2, suggesting
      that Asn-439, which is located in the second disulfide loop of the sixth EGF-like
      domain, is critical for determining the functional conformation of the EGF-like
      domains 4-6.

PMID- 7512387
TI  - The role of cyclic-3',5'-adenosine monophosphate in prostaglandin-mediated
      inhibition of basic calcium phosphate crystal-induced mitogenesis and collagenase
      induction in cultured human fibroblasts.
AB  - Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe
      destructive arthropathies characterised by synovial proliferation and non
      inflammatory degradation of intra-articular collagenous structures. BCP crystals
      stimulate fibroblast and chondrocyte mitogenesis, metalloprotease secretion and
      prostaglandin production. As a tissue protective effect of prostaglandins has
      been suggested, we recently studied the effect of PGE1 on BCP crystal-induced
      mitogenesis and collagenase mRNA accumulation in human fibroblasts (HF). We
      demonstrated a dose-dependent inhibition of BCP crystal-induced mitogenesis and
      collagenase mRNA accumulation. The mechanism of PGE1 inhibition of BCP crystal
      induced mitogenesis and collagenase mRNA accumulation was therefore explored.
      PGE1 (100 ng/ml) increased HF intracellular cAMP 40-fold over control. BCP alone
      caused no such change but inhibited the PGE1-induced increase in intracellular
      cAMP by at least 60%. The PGE1-induced increase in intracellular cAMP was also
      blocked by the adenyl cyclase inhibitor, 2',5'-dideoxyadenosine (ddA) (10 microM)
      and ddA reversed the PGE1-mediated inhibition of BCP crystal-induced mitogenesis.
      Dibutyryl cAMP also inhibited BCP crystal-induced mitogenesis in a concentration
      dependent manner. Agents which increase intracellular cAMP levels such as the
      adenyl cyclase activator forskolin and the phosphodiesterase, inhibitor 3
      isobutyl-1-methylxanthine (IBMX) mimicked the effect of PGE1 on HF collagenase
      mRNA levels. PGE1 inhibits the biologic effects of BCP crystals through the cAMP
      signal transduction pathway and such inhibition may have significant therapeutic
      implications.

PMID- 7512388
TI  - [Hepatitis C in hemophiliac patients in Maracaibo, Venezuela].
AB  - Infection with the hepatitis C virus is one of the risks of transfusion therapy.
      Considering that in Venezuela, there are not enough data that permit one to
      establish the frequency of hepatitis C in transfused patients, the purpose of
      this work was to investigate the presence of anti hepatitis C virus (HCV)
      antibodies in 56 hemophilic patients from Zulia State, Venezuela. Thirty six
      (64%) had received fresh frozen plasma and/or cryoprecipitate. Another fourteen
      (25%) also received lyophilized F VIII or prothrombin complex; six patients (10%)
      were never transfused. The positive samples (EIA 2nd. generation) were
      reconfirmed by RIBA-2. Twenty two of the patients were positive for HCV. The
      presence of anti-HCV antibodies was mainly detected in patients that received
      more than 10.000 U of the deficient factor. Four of the patients with HCV were
      also positive for the Human Immunodeficiency Virus (HIV). The results suggest
      that although the transfusion of blood derivatives carries the risk of HCV
      transmission, our patients show a low prevalence of this disease, probably due to
      the infrequent use of clotting factors lyophilizates.

PMID- 7512389
TI  - Intrafamilial transmission of hepatitis C virus.
AB  - The intrafamilial transmission pattern of hepatitis C virus (HCV) was examined in
      118 family members of 61 index patients with type C chronic liver disease using
      anti-HCV antibodies and HCV RNA assay. The study subjects consisted of eight
      parents, 49 spouses, 50 children, eight siblings and three other relatives. The
      positivity rates of anti-C100, anti-JCC, second-generation anti-HCV and HCV RNA
      were 6.8, 12.7, 12.7 and 11.0%, respectively. Positivity in one or more anti-HCV
      antibody assay was detected in 3/24 (12.5%) father-child pairs, 3/17 (17.6%)
      mother-child pairs, 2/8 (25%) sibling pairs, 6/38 (15.8%) husband-wife pairs and
      2/13 (15.4%) wife-husband pairs. In spouses, positivity for anti-HCV antibody or
      HCV RNA was observed after 40 years of age. None of 11 spouses married < 15 years
      was positive for any anti-HCV assay or HCV RNA. In spouses whose age was > 50
      years and duration of marriage was > 25 years, anti-HCV or HCV RNA was frequently
      detected (32.0%). However, when seven pairs involving four spouses, one mother
      daughter pair and two sibling pairs were subtyped, the same HCV subtypes were
      found in only four pairs (type II in three pairs and type III in one pair).
      Further, the agreement rate between anti-HCV and HCV RNA was > 90%. These results
      suggest that intrafamilial transmission of HCV, revealed by the subtyping method,
      is considered lower than the percentage of positivity for anti-HCV antibodies or
      HCV RNA in family members of patients with type C chronic liver disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7512390
TI  - Organization and transcription of the class I phycoerythrin genes of the marine
      cyanobacterium Synechococcus sp. WH7803.
AB  - The nucleotide sequences of the class I phycoerythrin (PE) alpha- and beta
      subunit genes (cpeA and cpeB) from the marine cyanobacterium Synechococcus sp.
      WH7803 are reported. The cpeB gene is located upstream of cpeA with a separation
      of 56 nucleotides and the two genes are co-transcribed as a transcript of 1.3 kb,
      with the transcription startpoint being localized to 110-111 bp upstream of cpeB.
      The sequence of the promoter region bears no similarity to promoters reported for
      other cyanobacterial PE genes. Pentanucleotide repeats found upstream of some PE
      operons, particularly in the case of cyanobacterial strains capable of chromatic
      adaption, are not found in Synechococcus sp. WH7803; instead the sequence 5'
      CGGTT-3' is repeated three times in the promoter region.

PMID- 7512391
TI  - The Geelong study.
AB  - The Geelong study is a prospective study of common abnormalities of pregnancy and
      birth and subsequent development. It outlines the prevalence and
      interrelationships of breath-holding attacks, febrile convulsions and non-febrile
      convulsions in the first 11 years of life. The interrelationship between febrile
      and non-febrile convulsions, behaviour and learning at 5 and 11 years is
      described. The predictive value of assessment at 5 years for later performance
      and behaviour at 11 years is also discussed.

PMID- 7512394
TI  - Study on the IL-5 expression in allergic nasal mucosa.
AB  - An immunohistological study was performed on allergic and nonallergic nasal
      mucosa to examine interleukin-5 (IL-5) expression. Many cells in the superficial
      portion of lamina propria expressed IL-5 in allergic nasal mucosa, whereas few
      cells expressed IL-5 in nonallergic mucosa. Furthermore, it was suggested by
      immunohistological double staining that CD45RO-positive cells, EG2-positive cells
      and metachromasia-positive cells expressed IL-5 in allergic nasal mucosa.

PMID- 7512392
TI  - Treatment of severe pertussis by administration of specific gamma globulin with
      high titers anti-toxin antibody.
AB  - Our patient presented with severe respiratory distress and marked pleocytosis.
      She was mechanically ventilated and received gamma globulin with high titers of
      anti-pertussis toxin and anti-filamentous hemagglutinin. Her clinical signs
      improved and a notable decrease in white blood cell count was observed. Ten
      months after treatment, the patient showed normal physical and mental development
      and anti-pertussis toxin and anti-filamentous hemagglutinin titers were
      significantly increased. Recently, the effectiveness of gamma globulin therapy
      has been emphasized again. Our experience supports the use of iv gamma globulin
      infusion. Also, gamma globulin did not influence the patient's own immunologic
      response to pertussis. Gamma globulin therapy with high anti-pertussis toxin
      titers could be considered for treatment of severe pertussis.

PMID- 7512393
TI  - Regulation of interleukin-5 production by peripheral blood mononuclear cells from
      atopic patients with FK506, cyclosporin A and glucocorticoid.
AB  - Upon stimulation with phorbol ester and ionomycin, peripheral blood mononuclear
      cells (PBMC) of atopic patients with moderate eosinophilia produced significantly
      higher amounts of IL-5 compared to that of normal subjects. This finding renders
      further support to the notion that T cell-eosinophilic inflammation plays a
      central role in allergic disorders. IL-5 induction in vitro was completely
      inhibited by immunosuppressant FK506, cyclosporin A and dexamethasone. FK506
      applied in vivo effectively suppressed clinical symptoms of atopic dermatitis and
      IL-5 production of PBMC. FK506 and cyclosporin A may become a better therapeutic
      modality against allergic diseases.

PMID- 7512395
TI  - Cytokine production in patients with mite-sensitive bronchial asthma.
AB  - We examined the eosinophil viability-enhancing activity (EVEA) of peripheral
      blood mononuclear cells (PBMNCs) obtained from mite-sensitive bronchial asthma
      (BA) and normal control subjects. Mite concentrations of 1 and 10 micrograms/ml
      significantly increased EVEA in BA patients as compared with normal controls (p <
      0.05 and p < 0.05, respectively). The level of IFN-gamma in PBMNC culture
      supernatants was higher in BA patients than in normal controls. Dexamethasone,
      cyclosporin A and FK506 significantly inhibited EVEA in BA patients (p < 0.05 to
      p < 0.001).

PMID- 7512396
TI  - Identification of the cytokine RANTES released from platelets as an eosinophil
      chemotactic factor.
AB  - Selective infiltration of eosinophils suggests the presence of the factors that
      attract eosinophils preferentially. Selective chemotactic polypeptides for human
      eosinophils were purified from thrombin-stimulated platelet supernatants and this
      chemotaxin was identified as the chemokine RANTES. The isolation of natural
      RANTES and its activity for eosinophil migration is summarized here. RANTES
      induced eosinophil migration at nanomolar range, in both chemotactic and
      chemokinetic manners. Specific desensitization experiments indicated that RANTES
      binds to receptors different from those for C5a and PAF, well-known potent
      eosinophil chemotaxins.

PMID- 7512397
TI  - RANTES augments radical oxygen products from eosinophils.
AB  - RANTES, which is released from thrombin-stimulated platelets, is a member of the
      8-kD cytokine family that has been shown to possess chemotactic activity for
      eosinophils. Thus, in this study, we examined the effect of RANTES on radical
      oxygen products from eosinophils. RANTES treatment resulted in the enhancement of
      peak value and integrated value of productivity of eosinophil-mediated radical
      oxygen products determined by luminol-dependent chemiluminescence of EoL-3 cells
      stimulated with A23187. In addition, the radical oxygen products of EoL-1 or
      eosinophils showed similar results. Thus, we could conclude that platelets might
      play an important role in the pathogenesis of allergic inflammation through the
      involvement in the selective eosinophil infiltration and eosinophil activation by
      releasing RANTES.

PMID- 7512398
TI  - The haemopoietic progenitor cell antigen.

PMID- 7512399
TI  - Occurrence of antibodies against chlamydial lipopolysaccharide in human sera as
      measured by ELISA using an artificial glycoconjugate antigen.
AB  - An artificial glycoconjugate containing, as a ligand, the deacylated carbohydrate
      backbone of a recombinant Chlamydia-specific lipopolysaccharide was used as a
      solid-phase antigen in ELISA to measure antibodies against chlamydial LPS. The
      specificity and reproducibility of the assay was shown by using a panel of
      prototype monoclonal antibodies representing the spectrum of antibodies also
      occurring in patient sera. These mAbs recognized Chlamydia-specific epitopes
      [alpha 2-->8-linked disaccharide of 3-deoxy-D-manno-octulosonic acid (Kdo) or the
      trisaccharide alpha Kdo-(2-->8)-alpha Kdo-(2-->4)-alpha Kdo] or those shared
      between chlamydial and Re-type LPS (alpha Kdo, alpha 2-->4-linked Kdo
      disaccharide). The assay was used to measure IgG, IgA and IgM antibodies against
      chlamydial LPS in patients with genital or respiratory tract infections. In
      comparison to the results obtained with sera from blood donors, it became evident
      that both types of infection result in significant changes in the profile of LPS
      antibodies.

PMID- 7512400
TI  - Epitope mapping human heat shock protein 90 with sera from infected patients.
AB  - Epitope mapping with sera from a range of infected patients showed that
      antibodies are commonly produced which cross-react with a number of epitopes on
      human heat shock protein 90 (HSP 90). Such autoreactive antibodies were
      particularly frequent in patients suffering from systemic candidiasis (9
      patients), invasive aspergillosis (6 patients), ABPA (2 patients), a patient with
      aspergilloma and one with malaria. The patient with malaria recognized similar
      epitopes to those with invasive aspergillosis and candidiasis including the
      highly conserved epitope LKVIRKVIRK and an epitope NNLGTI which was otherwise
      only recognised by patients with candidiasis. Crossreacting antibodies to
      relatively few epitopes occurred in patients with Enterococcus faecalis and
      Corynebacterium jeikeium endocarditis. This was contrasted with the results from
      6 patients with systemic lupus erythematosus (SLE) who were positive on
      immunoblot against fungal HSP 90. These did not react with the above epitopes but
      reacted with other areas within human HSP 90.

PMID- 7512401
TI  - Effect of terazosin on urine storage and voiding in the aging male with
      prostatism.
AB  - Patients in a private practice, evaluated for prostatism due to benign prostatic
      hypertrophy were offered the options of medical treatment with the alpha blocker
      terazosin, surgical treatment, or continued observation. Nineteen men accepted
      terazosin treatment and are the subjects of the present series. They were treated
      over a mean period of 8 months, the longest treatment lasting over 22 months.
      Dosage was started at 1 mg/d and increased as tolerated to 2, 5, and 10 mg/d over
      the test period. Extensive testing including invasive urodynamics, multiple
      voiding diaries, and symptoms scores at each dosage level was carried out. We
      found that flow rates increased moderately from baseline in a dose dependent
      fashion. At the 10 mg/d dosage some patients achieved flow rates in the low
      normal range. Patients on treatment documented a decrease in the number of
      voidings per day, a decrease in nocturia, an increase in bladder capacity and the
      volume of each voiding. On the other hand, patients frequently did not appreciate
      changes in their voiding patterns, as reflected in their responses to the symptom
      questionnaires. We could not demonstrate significant changes in bladder pressures
      on cystometry either during filling or voiding. Our data suggested that terazosin
      may well have a direct effect on the fundus of the aging bladder to increase
      capacity, and, through the well-known relationship between voided volume and flow
      rate, increase urinary flow rate.

PMID- 7512402
TI  - Subjective and objective evaluation of patients with prostatism and infravesical
      obstruction treated with both intraprostatic spiral and transurethral
      prostatectomy.
AB  - In order to evaluate the effect of intraprostatic spiral and subsequent
      transurethral prostatectomy (TURP) on obstructive benign prostatic hyperplasia, 9
      men were evaluated with symptom scores and urodynamic studies at inclusion after
      4 months of spiral treatment and 4 months after TURP. Six patients in a control
      group were evaluated at inclusion after an observation period of 4 months and 4
      months after TURP. After treatment with spiral the symptom score decreased in 7
      patients, increased in 1, and was unchanged in 1. After the observation period in
      the control group the symptom score decreased in 4 patients, increased in 1, and
      was unchanged in 1. After TURP the symptom score decreased even further in all
      patients, but one. After spiral treatment the urethral resistance decreased in 8
      of 9 patients, but according to Abrams and Griffith's [(1979): Br J Urol 51:129
      134] definition, only 2 were unobstructed. Five patients in the control group
      were unchanged obstructed after the observation period, while one was
      unobstructed. After TURP, the patients in both groups were all unobstructed.
      Intraprostatic spirals decrease the severity of symptoms and reduce the urethral
      resistance, but TURP in the same patient was much more effective.

PMID- 7512404
TI  - Two clusters of haemolytic uraemic syndrome in France.

PMID- 7512403
TI  - Laboratory acquired infection with Escherichia coli O 157.

PMID- 7512405
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7512406
TI  - Androgen manipulation and vasopressin binding in the rat brain and peripheral
      organs.
AB  - It is now widely recognized that there is a sexual dimorphism in the development
      of arginine vasopressin (AVP) immunoreactivity in certain parts of the brain, and
      that changes in brain AVP immunoreactivity change with manipulation of androgen
      status. The aim of this experiment was to determine specifically any AVP receptor
      changes in response to manipulation of androgen levels using a selective V1
      antagonist radioligand. Following castration, plasma testosterone levels fell and
      AVP immunoreactivity was reduced in the lateral septum and bed nucleus of the
      stria terminalis. With testosterone supplementation in castrated animals, the
      immunoreactivity in these regions was restored to a higher degree than in sham
      operated animals. Central and peripheral V1 AVP receptor binding (as determined
      using the selective AVP V1 antagonist radioligand [125I](d(CH2)5,sarcosine7)AVP
      was not changed in any of the brain regions studied or in liver or kidney
      membranes from the three groups. This study demonstrates that there is no change
      in brain AVP receptor binding despite changes in regional AVP immunoreactivity in
      the brain, and excludes any confounding interaction with changes in oxytocin
      receptors.

PMID- 7512407
TI  - The medical history of President Ronald Reagan.

PMID- 7512408
TI  - Autoantibodies in myositis.
AB  - Several autoantibodies are found specifically in myositis. Mostly this is
      myositis in the context of a connective tissue disease with associated features
      such as Raynaud's phenomenon, arthralgias, pulmonary fibrosis or scleroderma. The
      patterns of disease amount to overlap syndromes or subsets in which one can often
      predict the presence of a particular type of autoantibody. There are HLA
      associations, particularly with DQ alleles, related more closely to the antibody
      than to myositis overall. There is also a suggestion of seasonal and geographical
      variation within the United States distinguishing the advent of particular
      autoantibodies with the myositis. The myositis antigens are mainly
      ribonucleoprotein particles (RNA-protein complexes) functioning in RNA
      processing, protein translation and protein translocation into the endoplasmic
      reticulum. Within the cell the antigens are not accessible to antibody, with the
      possible exception that antibody to U(1)RNP may enter cells. If antibodies are to
      have a role in pathogenesis it is more likely to be through binding to cell
      membranes (there to activate complement or mediate T lymphocyte activity) or
      through immune complex mechanisms. The myositis antigen Ku has been detected on
      cell membranes, but generally in myositis there is scant deposition of
      immunoglobulin or complement in muscle except within small blood vessels. If
      autoantibodies really have little part to play in the pathogenesis of myositis
      their existence must relate to the earlier events of aetiology, like fingerprints
      on fragments of a terrorist's bomb.

PMID- 7512410
TI  - Paracelsus, scientific research and supportive care--500 years after!
AB  - The 500th anniversary of the birth of the famous Swiss physician and philosopher,
      Theophrastus Bombastus von Hohenheim--called Paracelsus, in the fall of 1993
      provides an excellent opportunity to review some of his thoughts and teachings
      and to reflect upon their timeless meaning for present-day medical research and
      patient care, especially in the sometimes controversial field of supportive care
      in oncology. Most probably Paracelsus' call for the abandonment of the encrusted
      dogmatic Galenism and his fight for a new spirit of experimental investigation by
      sound empirical studies was well ahead of his time in the early Renaissance.
      However, his concept of diseases as specific entities, relating to specific
      anatomical sites and possessing distinct and reproducible natural courses, was
      nearly prophetic, while still leaving room enough for individual variations. His
      views are somehow illustrative of modern psychosomatic medicine and comprehensive
      "holistic" supportive and palliative care, realized only after a very long
      "doctor's delay" at the close of the twentieth century.

PMID- 7512409
TI  - Canadian contributions to cancer control.
AB  - Cancer control comprises prevention, screening, treatment, rehabilitation and
      palliative care. Preventive approaches need to be congruent with those adopted
      for other chronic diseases, with a major impact to be expected from smoking
      control and dietary modification. Canadian studies have contributed substantially
      to knowledge in both areas. Increasing interest is now being paid to other
      environmental causes of cancer, and to gene-environment interactions. Canadian
      studies have shown that screening for cancer of the cervix is effective, but
      improved organization of services is required to make it realize its full
      potential. The National Breast Screening Study has reminded us that a
      prerequisite for effective screening is effective therapy for the detected
      abnormalities, yet as therapy improves, so the contribution of screening may
      fall. Treatment has improved dramatically in recent decades for childhood cancer,
      where it is the mainstay of control. For adults, Canadian studies have
      contributed to improved therapy for some solid and hematogenous tumors, but
      important breakthroughs from molecular biology are still awaited. Finally,
      Canadians have been at the forefront of palliative care, as well as recognizing
      the need for improvement in the organization of cancer control.

PMID- 7512411
TI  - Hypofractionation radiotherapy for a locally recurrent rectal carcinoma as a
      treatment for an elderly patient.
AB  - A very old patient, who had been suffering from rectal carcinoma for many years
      without achieving a complete response to electrocoagulations, was given
      palliative radiotherapy by hypofractionation with a total dose of 30 Gy in 3
      weeks, 1 fraction a week. A complete response was achieved. No special therapy
      related morbidity was noted. After the radiotherapy, an acceptable quality of
      life was maintained for 12 months without a local recurrence. It is concluded
      that radiotherapy may be a simple and efficient method of palliation without
      distressing morbidity compared with electrocoagulation.

PMID- 7512412
TI  - New directions in palliative care education.
AB  - In the past, palliative care education in the United Kingdom has tended to be
      patchy and ad hoc, rather that systematic and comprehensive. Recently the picture
      has begun to change, and this paper identifies and discusses three areas where
      developments are occurring. Firstly, educational provision has become more
      comprehensive and systematic, so that the needs of staff in all care settings and
      at all levels of practice and experience are now being addressed. Secondly,
      palliative nursing curricula that draw on research into the problems of nurses
      working with dying patients and the dimensions of the supportive role are now
      being developed. Thirdly, a number of initiatives are underway to assure the
      quality of palliative care education. Two of those initiatives concern the
      preparation, support and evaluation of educational roles and the development of
      educational research programmes.

PMID- 7512413
TI  - Ethical and professional issues in pain technology: a challenge to supportive
      care.
AB  - Pain management, a primary focus of oncology care, is undergoing a technological
      boom. This paper provides an overview of the ethical and professional issues
      facing health care providers in the use of pain technology. Ethical issues
      including the concepts of autonomy, beneficence, nonmaleficence, and justice are
      discussed in relation to pain management. The paper concludes with
      recommendations for clinical practice.

PMID- 7512414
TI  - Palliative care in high-tech medicine: defining the point of no return.

PMID- 7512415
TI  - Towards an optimal teaching programme for supportive care.
AB  - The changes occurring in medical education have led to important principles being
      identified that are relevant to teaching in supportive care. Many of these
      principles are already an integral part of the Newcastle, NSW, Medical Faculty
      undergraduate course and are being applied to the teaching of oncology and
      supportive care. The same principles can be applied to curriculum development and
      implementation in other settings. A curriculum is proposed that builds on a
      general background of oncology knowledge. Factual knowledge is limited to the
      precarious clinical problems requiring optimal supportive care, the priority
      oncology syndromes, palliative care and principles of psychosocial and
      behavioural science interventions. The curriculum also includes critical
      reasoning, special skills including counselling, communication, self-directed
      learning, team management, health-service resources and structure, and relevant
      management skills. To implement the curriculum, consideration must be given to
      teaching methods (teaching in context and in small groups, problem-based learning
      and problem solving). The needs of students, quality of the teachers, when and
      where the teaching and learning will occur and methods of assessment should also
      be considered to ensure the curriculum can be used optimally.

PMID- 7512417
TI  - Controversies in supportive care: destructive or beneficial diversity?

PMID- 7512416
TI  - Acute tumor lysis syndrome in poor-risk germ cell tumors: does it exist?
AB  - Acute tumor lysis syndrome (ATLS) is a well-known adverse event described after
      effective chemotherapy for extensive, highly proliferative, and chemosensitive
      tumors. While its occurrence with hematological malignancies is frequently
      described, there have been scattered case reports documenting ATLS in solid
      tumors. However, such events have not been reported in poor-risk germ cell
      tumors. We reviewed retrospectively 46 cases of such tumors treated in our
      department between 1988 and 1993 by aggressive cisplatin-based chemotherapy. All
      patients received systematically 6 l/24 h hydration according to the cisplatin-
      protocol administration. Blood chemistry data for potassium, phosphorus, calcium,
      alkaline reserve, uric acid, creatinine and lactate dehydrogenase were obtained
      before treatment and during the 7 days of the induction chemotherapy. No
      metabolic abnormalities suggestive of ATLS were observed. Nevertheless, 2
      patients with bulky disease of the chest experienced early death from respiratory
      distress complicated by multiorgan failure. ATLS seems to be an unlikely event in
      poor-risk germ cell tumors and therefore special prophylactic therapy may be
      unnecessary.

PMID- 7512418
TI  - Controversies in terminal cancer care.
AB  - In the long term, about 75% of all cancer patients will need palliative care, but
      the curricula in courses of study leading to qualifications in the caring
      professions take no account of this, being concerned exclusively with curative
      strategies. Precise definition of palliative care as a medical discipline is
      needed, followed by an insistence on proper funding and instruction. In addition,
      palliation should be integrated into the early stages of patient contact, e.g.,
      prevention, diagnosis, treatment planning, and not only implemented when attempts
      at curative therapy have failed. Public and political awareness must be promoted;
      in particular it should be recognized that the care givers themselves need
      support. There is a growing need for well-run hospices with purpose-trained
      staff. While "mercy killing" might be considered out of charity and humanity, the
      death of a terminally ill patient should be neither hastened nor postponed.

PMID- 7512419
TI  - Virus strategies for evasion of the host response to infection.
AB  - The attack on viruses and virus-infected cells by the mammalian immune system has
      provided considerable selective pressure for viruses that have evolved vigorous
      countermeasures to pre-empt, neutralize or evade this host attack. These
      countermeasures are astonishingly diverse, and their study imparts fundamental
      information about immunology and the mechanisms enabling viruses to survive and
      cause disease.

PMID- 7512420
TI  - Gates of Janus: cystic fibrosis and diarrhea.
AB  - Heat-stable enterotoxin, produced by Escherichia coli, binds to particulate
      guanylate cyclase to increase cyclic GMP in intestinal cells. This in turn
      stimulates the cyclic-GMP- or cyclic-AMP-dependent protein kinase, activating the
      same chloride channel that is defective in cystic fibrosis. It is possible that
      the relatively high prevalence of cystic fibrosis in humans results from its
      protective effect against diarrhea.

PMID- 7512421
TI  - Inhibitor regulation of tissue kallikrein activity in the synovial fluid of
      patients with rheumatoid arthritis.
AB  - Tissue kallikrein (TK) and alpha 1-antitrypsin (AT)/TK complexes can be detected
      in SF from patients with RA if components of the fluids which interfere with the
      detection of TK are removed. alpha 2-Macroglobulin (alpha 2-M) in SF was
      demonstrated to contain trapped proteases which were still active in amidase
      assays. Removal of alpha 2-M from RA SF reduced their amidase activity. However,
      at least some of the remaining activity was due to TK because it was soya bean
      trypsin inhibitor resistant and trasylol sensitive and was partly removed by
      affinity chromatography on anti-TK sepharose. Removal of RF from the fluids
      reduced the values obtained for TK levels by ELISA. Addition of SF to human
      urinary kallikrein (HUK) considerably reduced the levels of TK detected
      suggesting the presence of a TK ELISA inhibitor in the fluids. Removal of
      components of > 300 kDa from SF markedly reduced the TK ELISA inhibitory activity
      and increased the values for both the TK and alpha 1-AT/TK levels in fluids as
      measured by ELISA. It is considered this novel inhibitor does not bind to the
      active site of TK but rather binds to the site reactive with anti-TK antibodies.

PMID- 7512422
TI  - Polyarthritis associated with hepatitis C virus infection.
AB  - Two cases of polyarthritis associated with hepatitis C infection are reported. In
      Patient 1, stiffness and polyarthritis occurred during the acute stage of
      hepatitis. The arthritic symptoms lasted for 4 months. A transient polyarthritis
      recurred 4 yr later. The persistent presence of anti-hepatitis C viral antibodies
      was noted. Hepatitis C viral RNA (HCV RNA) was identified in the serum using the
      polymerase chain reaction proving that the patient was a carrier. In Patient 2,
      polyarthritis occurred associated with chronic hepatitis C liver disease.
      Synovial biopsy showed infiltration of mononuclear cells. HCV RNA was
      demonstrated in both serum and SF. These cases suggest an aetiologic association
      between arthritis and hepatitis C antigenaemia.

PMID- 7512423
TI  - Hepatitis C virus and mixed cryoglobulinaemia.

PMID- 7512424
TI  - Interleukin-1 production by activated macrophages surrounding loosened
      orthopaedic implants: a potential role in osteolysis.
AB  - IL-1 producing cells at the bone-implant interface obtained during revision of
      loosened total joint replacements were demonstrated by immunohistochemistry on
      tissue sections. Other markers for the characterization of macrophages, B cells,
      T cell subpopulations, IL-2 receptor and HLA-DR antigens were also used. The 10
      cases examined showed excessive metallosis within the cytoplasm of the
      macrophages and extracellular matrix. IL-1 beta containing cells were found in
      seven cases, four of which showed positive staining on more than 80% of the
      macrophages. A relatively similar proportion of T cells was seen in all the
      cases. T helper (CD4 positive) cells were always present in excess of T
      suppressor (CD8 positive) subtype. T cells showed no expression of detectable
      membrane IL-2 receptor. No B cells were found in these cases. Macrophages showed
      very strong immunostaining for HLA-DR. These findings indicate the possible
      induction of IL-1 production by activated macrophages in the interface in
      response to the presence of metallic wear debris. In view of the well known
      effect of IL-1 as a potent mediator of bone lysis, the results suggest a major
      role of the metal debris-containing macrophages in the process of osteolysis and
      subsequent implant loosening.

PMID- 7512425
TI  - Regrowth of dorsal root axons into a radiation-induced glial-deficient
      environment in the spinal cord.
AB  - Exposure of the lumbosacral spinal cord of early postnatal rats to X-rays reduces
      the glial populations within the irradiated region. The present study examines
      the ability of axons of a dorsal root subjected to a crush-freeze lesion to grow
      back into this glial-deficient spinal cord environment, in contrast to the non
      irradiated rat. Ultrastructural examination of the dorsal root entry zone (DREZ)
      60 days after root injury revealed a well-formed astrocytic scar in this zone and
      adjacent regions of spinal cord in non-irradiated rats. In contrast, scar
      formation did not occur in irradiated root-lesioned animals in which the
      astrocytic response was quite limited. Axons were present in the DREZ and
      underlying spinal cord in irradiated root-lesioned rats at this time but were
      absent from these regions in the non-irradiated lesioned controls. These
      ultrastructural findings are highly suggestive that axons are capable of regrowth
      into the irradiated spinal cord. Axonal regrowth was assessed further by tracing
      techniques after application of a combination of peroxidase-labeled wheat germ
      agglutinin and horseradish peroxidase to the cut end of the root distal to the
      previously injured site. Labeled axons were readily identified within the spinal
      gray matter in irradiated lesioned but not in the non-irradiated lesioned rats.
      These data, together with the ultrastructural observations, are supportive of
      regrowth of the dorsal root axons into the spinal cord. The radiation-induced
      changes in the glial populations are discussed with regard to conversion of a
      normally non-permissive environment into one conducive for axonal regrowth.

PMID- 7512426
TI  - Galanin-(1-15), but not galanin-(1-29), modulates 5-HT1A receptors in the dorsal
      hippocampus of the rat brain: possible existence of galanin receptor subtypes.
AB  - The aim of the present study was to evaluate whether galanin-(1-29) and galanin
      (1-15) can modulate the 5-hydroxytryptamine1A (5-HT1A) receptors using [3H]8-OH-2
      (di-n-propylamino)-tetralin ([3H]8-OH-DPAT) as a radioligand. Membrane
      preparations of the dorsal hippocampus, an area having the recently described
      [125I]galanin-(1-15) fragment binding sites, but having very few porcine
      [125I]galanin-(1-29) binding sites, were used. Galanin-(1-15) produced a
      concentration-dependent increase in the Kd value of [3H]8-OH-DPAT with a maximum
      effect of approximately 65% at 3 nM of galanin-(1-15), whereas galanin-(1-29) had
      no effect. This increase of the Kd value of [3H]8-OH-DPAT could be completely
      counteracted by the putative galanin antagonist M35 (1 nM). The Bmax values of
      [3H]8-OH-DPAT were not affected in any experiment. In conclusion, the present
      results give further evidence for the existence of a galanin receptor subtype
      mainly recognizing N-terminal galanin fragments, also having the ability to
      reduce the affinity of 5-HT1A receptors.

PMID- 7512427
TI  - Intrahippocampal administration of the NO synthase inhibitor L-NAME prevents
      working memory deficits in rats exposed to transient cerebral ischemia.
AB  - A 5-min period of cerebral ischemia increased the number of errors in a working
      memory task with three-panel runway paradigm, while it had no effect on reference
      memory errors. The nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine
      methyl ester (L-NAME), infused into the bilateral dorsal hippocampus at 100
      micrograms/side immediately after blood flow reperfusion, significantly reduced
      the increase in working memory errors expected to occur 24 h after 5 min of
      ischemia. Intrahippocampal administration of the inactive isomer D-NAME at 100
      micrograms/side immediately after reperfusion had no effect on the increase in
      working memory errors in the ischemic rats. These findings suggest that the
      mechanism mediated by hippocampal NO synthesis during the early reperfusion phase
      contributes to the postischemic impairment of working memory.

PMID- 7512428
TI  - Immunohistochemical localization of glutamate and glutaminase in guinea pig
      trigeminal premotoneurons.
AB  - Previous electrophysiological experiments in guinea pigs from our laboratory
      [11,36,37] have suggested that synaptic transmission between last-order
      interneurons (premotoneurons) and trigeminal motoneurons during reflex activation
      or cortically induced rhythmical jaw movements is mediated by excitatory amino
      acids (EAAs). In the present study, we performed a series of double-labeling
      experiments in guinea pigs to determine the location of neurons which contain
      glutamate or glutaminase and project to the trigeminal motor nucleus (Mo5). This
      was accomplished by combining immunohistochemical staining and standard
      retrograde tract-tracing techniques. Injections of a retrograde tracer, colloidal
      gold bound to inactivated WGA-HRP (gWGA-HRP), into the trigeminal motor nucleus
      labeled a column of neurons originating adjacent to Mo5, including the
      supratrigeminal nucleus, intertrigeminal nucleus and the mesencephalic nucleus of
      V. The column extended caudally into the parvocellular reticular formation and
      adjacent trigeminal sensory nucleus oralis and oralis gamma subdivision. In all
      of these regions, immunoreactivity to glutamate or glutaminase was observed co
      localized with gWGA-HRP.

PMID- 7512429
TI  - Nerve growth factor administration protects against experimental diabetic sensory
      neuropathy.
AB  - Small fiber sensory neuropathy is one of the most common complications of
      diabetes mellitus. Currently there is no adequate therapy to prevent this often
      debilitating problem. Nerve growth factor (NGF) is a protein that promotes the
      survival and integrity of a large percentage of sensory neurons including the
      small fiber pain transmitting neurons which are often prominently affected in
      diabetic neuropathy. We report here that exogenously administered NGF is capable
      of preventing the behavioral and biochemical manifestations of diabetic sensory
      neuropathy in a streptozocin induced rat model. NGF administration prevented the
      elevation of tailflick threshold (a measure of the rat's response to a thermal
      noxious stimulus) which occurred in streptozocin-induced diabetic rats. Further,
      it prevented the induced reduction in levels of the neuropeptides substance P and
      calcitonin gene related peptide measured from cervical dorsal root ganglia.
      Finally, NGF did not ameliorate the prolonged latency of the compound action
      potentials measured from the caudal nerve of the tail. In view of these results,
      a clinical trial of NGF in diabetic neuropathy has now commenced.

PMID- 7512430
TI  - The paragigantocellular nucleus of the ventral medulla: a secondary source of
      cholinergic innervation of rat brainstem nuclei.
AB  - Many parts of the brainstem are known to be innervated by the cholinergic neurons
      of the pontomesencephalic tegmentum, but other possible sources of this
      innervation have rarely been considered. We sought to examine whether other cells
      in the brainstem were responsible for this cholinergic input using axonal tract
      tracing and choline acetyltransferase (ChAT) immunocytochemistry. The results
      confirm previous studies on the projections of the neurons of the
      pontomesencephalic tegmentum but also show that a group of ChAT-positive cells in
      the paragigantocellular nucleus in the ventral medulla are a source of
      widespread, albeit less substantial cholinergic projections to several areas of
      the brainstem.

PMID- 7512431
TI  - On the regional distribution of heparan sulfate proteoglycan immunoreactivity in
      the rat brain.
AB  - By means of two monoclonal antibodies specific for heparan sulfate (HS)-related
      epitopes, one (10E4) against native HS chains and one (3G10) against desaturated
      uronates, a highly regional and differential distribution of these two epitopes
      have been observed in the adult rat brain. The 10E4 epitope immunoreactivity (IR)
      is mainly found in the substantia nigra, the red nucleus and the subgranular zone
      of the dentate gyrus, while the 3G10 epitope IR is mainly found in the CA2 area
      of the hippocampal formation and the pyramdial cells in the layer V of the
      frontoparietal cortex. The codistribution of both types of IRs with basic
      fibroblast growth factor (bFGF, FGF-2) in neurons and astroglia supports the
      notion that heparan sulfate proteoglycans (HSPG) in the extracellular matrix may
      serve as a site for storage of bFGF and assist in the bFGF-induced activation of
      the high-affinity FGF receptors linked to astroglia and neurons in these discrete
      areas.

PMID- 7512432
TI  - Stimulation of N-methyl-D-aspartate receptors in the rat nucleus reticularis
      thalami suppresses somatosensory evoked potentials.
AB  - The role of excitatory amino acid receptors in the rat nucleus reticularis
      thalami (NRT) for the modulation of cortical somatosensory evoked potentials
      (SEPs) was examined. The effects of microapplication of N-methyl-D-aspartate
      (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), an
      agonist at the non-NMDA receptors, into the NRT on the amplitude and latency of
      cortical SEPs were measured. SEPs were recorded from the somatosensory cortex of
      anaesthetized rats, in response to single shock stimulation of the contralateral
      forepaw. Injection of NMDA into the NRT resulted in a decrease in amplitude and
      increase in latency of SEPs. These effects were dose-dependent over the range
      from 0.05 to 0.5 nmol. Co-administration of (-)-2-amino-7-phosphono-heptanoate, a
      specific NMDA antagonist, with NMDA into the NRT prevented these changes. The
      depressant action of NMDA on cortical SEPs was site-specific for the NRT.
      Application of AMPA into the NRT did not affect cortical SEPs. The present
      results are in line with the assumption that an excitatory amino acid serves as
      transmitter to stimulate NRT neurons which in turn leads to suppression of
      cortical SEPs. NMDA receptors within the NRT appear to be involved in this
      depressant action.

PMID- 7512433
TI  - Effects of acute injection of methylprednisolone in man on immunological and non
      immunological histamine release from leucocytes and its potentiation by
      interleukin-3.
AB  - We investigated the effects of intravenous injection of methylprednisolone (MPR)
      compared with placebo (saline) on ex vivo leucocytic histamine release in eight
      healthy volunteers. All subjects received in a randomized and a single-blind
      manner the placebo and MPR, 20 mg and 125 mg, each injection given in 2 week
      intervals. On each occasion blood samples were taken just before and 24 h after
      the intravenous injection to determine circulating leucocyte counts and
      leucocytic histamine release induced by anti-IgE (1/2000) and FMP (Formyl
      Methionyl-Phenylalanine) (10(-5) M) and its modulation by IL-3 (2 ng/ml). MPR 20
      mg and 125 mg significantly increased circulating leucocyte counts (P < 0.05 and
      P < 0.001 respectively) but decreased leucocytic histamine content (P < 0.05 and
      P < 0.001 respectively) by 24 h. Placebo had no effect. As for circulating
      basophils, after 24 h they were decreased by 125 mg MPR (P < 0.05) but increased
      by 20 mg (P < 0.05). Anti-IgE-induced HR was significantly inhibited by 125 mg
      MPR (P < 0.05) but not by 20 mg MPR or by the placebo. In contrast, neither MPR
      (20 mg and 125 mg) nor placebo significantly reduced FMP-induced HR. The strong
      potentiation by IL-3 of HR evoked by anti-IgE and FMP at baseline (P < 0.001)
      persisted 24 h after injection of MPR or placebo (P < 0.001 except P < 0.05 for
      anti-IgE-induced HR after 125 mg MPR).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512434
TI  - Ionic regulation of human basophil releasability. II. Non-releasing basophils are
      converted into releasing basophils in a low-Na+ medium.
AB  - The effects of different extracellular Na+ and Ca2+ concentrations on histamine
      release from human basophils were investigated. Isosmotic replacement of
      extracellular Na+ either with choline+, a non-permeant Na+ analogue, or glucose
      significantly increased spontaneous and anti-IgE-induced histamine release.
      Basophils from 12 of 49 normal subjects, which were found not to release
      histamine upon challenge with an optimal dose of anti-IgE in a 135 mM NaCl
      buffer, were converted into releasing basophils when stimulation with anti-IgE
      was performed in a low-Na+ medium. The increase in Na+ concentration in the
      extracellular medium was accompanied by a reduction in the magnitude of basophil
      response to anti-IgE, which was significantly more pronounced in non-releasers
      than in releasers (per cent inhibition by 70 mM NaCl 75.5 +/- 3.2 vs 43.5 +/-
      9.0, P < 0.01). At higher Na+ concentrations a progressive and almost complete
      abrogation of histamine release was observed in non-releasers, but not in
      releasers (maximal per cent inhibition at 140 mM NaCl 97.3 +/- 1.3 vs 50.4 +/-
      8.6). The Na+/H+ exchanger monensin had a dose-dependent inhibitory effect on
      anti-IgE-induced histamine release, and the concentration inhibiting 50% of
      histamine release was 1.5 x 10(-7) M. When basophils were challenged in the
      presence of different Na+ and Ca2+ concentrations, it was shown that the two
      cations have antagonistic effects, which is to say that they down-regulate and
      upregulate histamine release, respectively. Moreover, the requirement of
      extracellular Ca2+ was lowered in a low-Na+ medium.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7512435
TI  - Clear cell eccrine carcinomas of the skin. A clinicopathologic study of nine
      patients.
AB  - BACKGROUND: Sweat gland carcinomas with clear cell features are extremely rare
      neoplasms, with few well documented cases reported in the literature. METHODS:
      Data on nine patients with malignant eccrine adnexal neoplasms characterized by a
      prominent clear cell neoplastic component were studied. Immunohistochemical
      stains with a panel of antibodies against epithelial, stromal, and neural
      antigens were performed on five tumors and electron microscopic examination of
      one. RESULTS: The tumors showed a spectrum of histologic features and growth
      patterns that ranged from well differentiated, low grade malignant neoplasms to
      poorly differentiated, highly aggressive, recurrent, and metastasizing tumors.
      All tumors contained a varied proportion of cells with abundant clear cytoplasm,
      similar to those seen in a group of benign eccrine adnexal neoplasms that have
      been variously designated as clear cell hidradenoma, nodular hidradenoma, clear
      cell myoepithelioma, and eccrine acrospiroma. Immunohistochemical stains on five
      tumors and ultrastructural examination in one were consistent with eccrine
      differentiation. Clinical follow-up of eight patients showed local recurrence in
      six, followed by metastases in three, despite local excision, radiation, and
      chemotherapy. Criteria for differentiating these tumors from their benign
      counterparts and from other types of malignant adnexal neoplasms and metastatic
      lesions are presented. CONCLUSIONS: The findings indicate that clear cell eccrine
      carcinomas comprise a heterogeneous group of lesions that may range from locally
      recurring, low grade well differentiated tumors to highly aggressive, high grade
      tumors with a definite potential for uncontrollable local recurrence and
      metastasis. Wide surgical excision is recommended as the primary treatment for
      such neoplasms.

PMID- 7512436
TI  - High-dose doxorubicin, etoposide, and cyclophosphamide with stem cell reinfusion
      in patients with metastatic or high-risk primary breast cancer. City of Hope Bone
      Marrow Oncology Team.
AB  - BACKGROUND: Chemotherapy with a doxorubicin-containing regimen results in high
      overall response rates in the treatment of metastatic adenocarcinoma of the
      breast; the combination of doxorubicin, etoposide, and cyclophosphamide has
      produced a response rate of 84% in untreated patients with stage IV disease.
      Recent data suggest that selected groups of patients with metastatic disease
      treated with high-dose chemotherapy and stem cell support may enjoy unmaintained,
      long-term remission. This study was designed to establish the feasibility of
      administering the combination of high-dose infusional doxorubicin, etoposide, and
      cyclophosphamide followed by autologous stem cell rescue in patients with
      responsive metastatic, or high-risk primary breast cancer. METHODS: Criteria for
      patient enrollment included the presence of high-risk primary breast cancer
      (stage II with > or = 10 involved axillary nodes or stages III A or B) or stage
      IV disease in complete or partial response; Karnofsky performance status of 80%
      or more; no prior radiation therapy to the left side of the chest; exposure to a
      150-mg/m2 or smaller cumulative dose of doxorubicin, and a ventricular ejection
      fraction of 55% or more. Chemotherapy consisted of escalating doses of
      doxorubicin given by a 96-hour continuous intravenous infusion, followed by 60
      mg/kg of etoposide and 100 mg/kg cyclophosphamide, both given intravenously. On
      Day 0, autologous bone marrow with or without peripheral stem cells, or
      granulocyte colony-stimulating factor primed peripheral stem cells alone were
      reinfused. RESULTS: Thirty-five patients were treated in this study. There were
      no treatment-related deaths. No patient had a decrease in cardiac ejection
      fraction below 50% as a consequence of high-dose chemotherapy. Two patients
      suffered grade 3 mucositis at the highest level of doxorubicin (200 mg/m2). Of 21
      patients treated for primary high-risk breast cancer, 19 are recurrence free,
      with a median follow-up of more than 8 months (> or = 4-36 months). Five of
      fourteen patients with stage IV disease remain progression free at greater than
      or equal to 5, 7, 9, 15, and 42 months. For patients with stage IV breast cancer,
      the median progression-free survival after high-dose chemotherapy was 9 months;
      the median overall survival had been reached at 22 months. CONCLUSIONS: The phase
      II dose of doxorubicin in this combination therapy has been established at 165
      mg/m2, with dose-limiting toxicity defined as mucositis. Further trials to define
      the role of this safe and effective high-intensity regimen in the treatment of
      breast cancer are indicated.

PMID- 7512437
TI  - Evaluation of survival after second-line intraperitoneal cisplatin-based
      chemotherapy for advanced ovarian cancer.
AB  - BACKGROUND: The authors sought to evaluate survival of patients with ovarian
      cancer treated with second-line intraperitoneal cisplatin-based chemotherapy.
      METHODS: From August 1985 to September 1991, 63 patients with recurrent or
      persistent ovarian cancer after first-line cisplatin-based chemotherapy were on a
      protocol and treated with cisplatin, cytarabine, with or without bleomycin.
      Eligibility included Stage III/IV invasive adenocarcinoma of the ovary,
      documentation of the size of residual disease at reoperation, and prior treatment
      with first-line intravenous cisplatin-based chemotherapy. RESULTS: The median
      survival from intraperitoneal chemotherapy was 29 months. For patients who
      responded to first-line chemotherapy and second-line intraperitoneal
      chemotherapy, the 5-year survival was 60%, but for patients with response to
      first-line chemotherapy but no response to intraperitoneal chemotherapy the 5
      year survival was only 17%, and no patient survived 5 years who did not have a
      response to first- or second-line therapy (P < 0.0001). There was significant
      improvement in the 2-year survival from initiation of intraperitoneal
      chemotherapy for patients with < or = 5 mm residual tumor in greatest dimension
      (74%), compared with patients with residual tumor larger than 5 mm and smaller
      than or equal to 2 cm (38%), and patients with residual tumor larger than 2 cm
      (0%) (P < 0.0001). CONCLUSION: Survival was increased for patients who (1) had a
      response to first-line intravenous chemotherapy and second-line intraperitoneal
      chemotherapy and (2) who had residual tumor 5 mm or smaller at the initiation of
      intraperitoneal therapy. The conclusion that the prolonged survival is secondary
      to cisplatin-based chemotherapy administered intraperitoneally must be made with
      caution because survival may have been secondary to the small residual disease at
      initiation of second-line chemotherapy or the systemic effect of cisplatin.

PMID- 7512438
TI  - Early salvage therapy for germ cell cancer using high dose chemotherapy with
      autologous bone marrow support.
AB  - BACKGROUND: Patients with relapsed germ cell cancer (GCT) have a poor prognosis
      when treated solely with conventional chemotherapy; high dose chemotherapy with
      autologous bone marrow rescue (ABMR) has shown curative potential in patients
      with relapsed and refractory GCT. This protocol was designed to incorporate high
      dose therapy with initial salvage therapy. METHODS: Twenty-three patients in the
      first relapse of GCT received two cycles of conventional dose cisplatin-based
      therapy (either vinblastine, ifosfamide and cisplatin [VeIP] or cisplatin,
      vinblastine, and bleomycin) followed by carboplatin (1500-2100 mg/m2) and
      etoposide (1200-2250 mg/m2) given in divided doses with ABMR. RESULTS: Eighteen
      of 23 patients completed protocol therapy including high dose therapy. Five of 23
      did not undergo high dose therapy due to: insurance refusal (1); patient refusal
      (1); active infection (1); central nervous system metastasis (1); death on
      induction therapy (1). Response to two courses of conventional dose induction
      therapy (N = 23) was complete response (CR), 8; partial response (PR), 12; stable
      disease (SD), 2; and toxic death, 1. Two of five individuals who did not continue
      with high dose therapy are alive and progression free after conventional salvage
      therapy and surgery with at least 24 months of follow-up. Outcome after high dose
      therapy (N = 18) was CR, 9, PR, 6, SD, 1, and PD, 2. Two patients who were in PR
      after receiving two cycles of conventional dose therapy were converted to CR
      using high dose therapy. There was only one treatment-related death in this
      cohort, a septic death during VeIP induction therapy. There were no transplant
      related deaths. Of those patients completing high dose therapy, 7 of 18 (39%)
      survived, progression free with a median follow-up of 26 months, 2 of 18 are
      alive with active disease, and 9 of 18 died of recurrent disease. CONCLUSIONS:
      Conventional dose induction therapy followed by consolidation with high dose
      therapy and ABMR is well tolerated and provides prolonged disease-free survival
      in some patients with chemosensitive relapsed germ cell cancer.

PMID- 7512439
TI  - Desmoplastic small round cell tumors of the abdomen.
AB  - BACKGROUND: Desmoplastic small round cell tumors (DSRCT) have been only recently
      identified. METHODS: The authors report DSRCT in two pediatric patients (an 8
      year-old boy and 12-year-old boy). In both patients, the initial diagnosis was
      rhabdomyosarcoma. The resistance to standard chemotherapy and radiation therapy
      prompted the authors to review the initial biopsy specimens and perform
      complementary immunophenotypic characterization. RESULTS: These analyses revealed
      that the tumor cells were strongly positive for keratin epithelial marker
      antigen, desmin, vimentin, neurospecific enolase, and S100 protein, corresponding
      to pleomorphic differentiation, characteristic of DSRCT: CONCLUSIONS: The authors
      suggest that extensive immunohistologic characterization be performed in all
      cases of small round cell tumors of the abdomen so that the diagnosis of DSRCT is
      not overlooked. These rare tumors are refractory to chemotherapy, and initial
      aggressive surgery is warranted.

PMID- 7512441
TI  - Primary lymphoma of the ampulla of Vater.
AB  - A 57-year-old woman was investigated for obstructive jaundice with endoscopic
      retrograde cholangiopancreaticography that showed a tumor at the ampulla of
      Vater. A Whipple's procedure was performed. A protuberant tumor was present at
      the ampulla of Vater in the background of multiple mucosal polyps in the
      duodenum. Light microscopy revealed a diffuse non-Hodgkin's lymphoma with
      centrocytelike cells forming lymphoepithelial lesions and infiltrating the
      sphincter of Oddi. The duodenal polyps were hyperplastic lymphoid follicles with
      reactive germinal centers. Immunohistochemical staining characterized the tumor
      as a B-cell neoplasm with IgA heavy-chain and lambda light-chain restrictions.
      Complete remission of the disease occurred after surgery. The clinical,
      histologic, and immunohistochemical features of this lymphoma are suggestive of
      histogenetic derivation from mucosal-associated tissue.

PMID- 7512440
TI  - The frequency of a concomitant early esophageal cancer in male patients with oral
      and oropharyngeal cancer. Screening results using Lugol dye endoscopy.
AB  - BACKGROUND: Male patients with oral and oropharyngeal cancer are known to have
      high risk of concomitant esophageal cancer developing. Thus, mass screening
      programs are pursued to detect such esophageal cancer early, and in a mass
      screening trial of patients with early oral and oropharyngeal cancer, the
      efficacy of Lugol dye endoscopy for detecting concomitant esophageal cancers has
      been evaluated. METHODS: Lugol dye was used in an endoscopic screening of 101
      patients with oral cancer and 26 with oropharyngeal cancer; all of the patients
      were men. RESULTS: Among these 127 patients, eight (6.3%) clinical asymptomatic
      concomitant esophageal cancers were detected, and four of these eight cancers
      were found in the patients with oropharyngeal cancer. Five of these eight
      superficial lesions could not be detected by ordinary endoscopy or barium study.
      CONCLUSION: Our results show that Lugol dye endoscopy is indispensable for
      monitoring male patients with oral or oropharyngeal cancer to detect an early
      concomitant esophageal cancer. In addition, a higher frequency of concomitant
      esophageal cancer was seen in the patients with oropharyngeal cancer than in the
      patients with oral cancer.

PMID- 7512442
TI  - Recurrent granulocytic sarcoma. An unusual variation of acute myelogenous
      leukemia associated with 8;21 chromosomal translocation and blast expression of
      the neural cell adhesion molecule.
AB  - This study reports on a patient with acute myelogenous leukemia (AML) in
      remission who had a series of 11 granulocytic sarcomas (chloromas or
      myeloblastomas) appearing periodically over a 29-month interval in a variety of
      anatomic sites without evidence of bone marrow recurrence. This isolated
      extramedullary recurrence of AML is distinctly unusual with only 24 cases
      described previously. This patient had the greatest number and longest reported
      interval of recurrent granulocytic sarcomas (GS) before bone marrow relapse.
      Furthermore, he represents the first case of a patient with GS presenting with
      both an 8;21 chromosomal translocation and neural cell adhesion molecule (CD56)
      expression. The authors hypothesize that these two abnormalities identified
      previously as predisposing factors to GS may, in fact, be synergistic for this
      phenomenon. His case and the review of the literature demonstrate some of the
      important clinical and management features of a patient who develops GS while in
      complete marrow remission from previous AML. Although highly sensitive to
      radiation therapy, the onset of granulocytic sarcomas is almost always followed
      by bone marrow relapse and should be treated with aggressive reinduction
      chemotherapy and local irradiation. Such therapy is associated with the longest
      interval of disease-free survival.

PMID- 7512443
TI  - The distribution of cellular adhesion molecules in pigmented skin lesions.
AB  - BACKGROUND: The process of multistep tumor development has been studied
      thoroughly in the development of malignant melanomas. The authors investigated
      the expression of cellular adhesion molecules in nevomelanocytic lesions to
      explore a postulated role of adhesion molecules in cell-cell and cell-matrix
      interactions during tumor development. METHODS: Sections of 20 nevocellular nevi,
      35 dysplastic nevi, 6 melanomas in situ, and 20 malignant melanomas were
      investigated with respect to their expression of intercellular adhesion molecule
      1 (ICAM-1), inducible cell adhesion molecule-110 (INCAM-110)/vascular cell
      adhesion molecule-1 (VCAM-1), E-selectin, lymphocyte function-associated antigen
      1 (LFA-1), and the integrins for very late antigen-(VLA) alpha-(alpha) 2 and VLA
      alpha 6; for these studies, monoclonal antibodies were used and indirect
      immunoperoxidase and immunofluorescence staining methods were performed. RESULTS:
      In the transformation from benign to malignant neoplasms, the expression of ICAM
      1 was upregulated strongly. The expression of VLA-alpha 2 on tumor cells
      increased whereas that of VLA-alpha 6 decreased; these alterations corresponded
      to changes previously observed in their ligands within the extracellular matrix.
      These results were statistically significant. In addition, ICAM-1, INCAM-110/VCAM
      1, and E-selectin were detected in activated endothelial cells, probably as a
      result of cytokine activation. The ligand for ICAM-1, LFA-1, was confined to
      mononuclear cells. CONCLUSIONS: The increase in ICAM-1 and VLA-alpha 2 expression
      and the decrease of VLA-alpha 6 expression may, in combination with specific
      matrix alterations, lead to a change in cell-cell and cell-matrix interaction,
      thereby contributing to the invasive property of melanocytic tumor cells. The
      neoexpression of INCAM-110/VCAM-1 and E-selectin in pigmented skin lesions may
      play a role in both infiltrative growth and the generation of a host reaction
      toward these tumors.

PMID- 7512444
TI  - The structure of the O-specific polysaccharide of Salmonella arizonae O62.
AB  - The O-specific polysaccharide was liberated by mild acid hydrolysis of the
      lipopolysaccharide (LPS) isolated from S. arizonae O62 by phenol-water
      extraction. The branched hexasaccharide repeating-unit of the O-specific chain of
      the O62 LPS contained L-rhamnose, 2-acetamido-2-deoxy-D-glucose, and 2-acetamido
      2-deoxy-D-galacturonic acid in molar ratios of 4:1:1. On the basis of methylation
      analysis, 1H and 13C NMR spectroscopy, including 2D shift-correlated (COSY) and
      1D NOE spectroscopy, the following structure for the repeating unit of the O
      specific polysaccharide was established: [formula: see text]

PMID- 7512445
TI  - Structure of the capsular polysaccharide and the O-side-chain of the
      lipopolysaccharide from Acetobacter methanolicus MB 70, and of oligosaccharides
      resulting from their degradation by the bacteriophage Acm6.
AB  - Acetobacter methanolicus MB 70 was shown to be related to the type strain of this
      species MB 58/4 (IMET 10945) having the same galactan-->2)-beta-D-Gal f-(1-->3)
      beta-D-Gal p-(1-->as the capsular polysaccharide (CPS) and the O-side-chain of
      the lipopolysaccharide (LPS). Additionally, a glucan built up of the disaccharide
      repeating unit-->6)-alpha-D-Glc p-(1-->2)-alpha-D-Glc p-(1-->was identified in
      strain MB 70. In the CPS, the polymers were present in the ratio approximately
      1:1, whereas the glucan preponderated in the LPS. Bacteriophage Acm6 specific to
      A. methanolicus MB 70 hydrolysed selectively the glucan component of both CPS and
      LPS. Structural elucidation of the resulting oligosaccharides led to the
      identification of the phage-associated depolymerase as an endo-alpha-(1-->6)-D
      glucopyranoside hydrolase.

PMID- 7512446
TI  - Structure of the capsular polysaccharide and the O-side-chain of the
      lipopolysaccharide from Acetobacter methanolicus MB 135 (IMET 11402).

PMID- 7512447
TI  - Cariogenic potential of foods. II. Relationship of food composition, plaque
      microbial counts, and salivary parameters to caries in the rat model.
AB  - A series of rat caries experiments was carried out to test the relative
      cariogenic potential and to identify the major carcinogenic elements of 22
      popular snack foods. Parameters that were measured included rat caries, number of
      cariogenic bacteria in plaque, salivary parameters including flow rate, buffering
      capacity, total protein, lysozyme and amylase content, and composition of test
      foods including protein, fat, phosphorus, calcium, fluoride, galactose, glucose,
      total reducing sugar, sucrose, and starch. Many interesting relationships were
      observed between food components, numbers of plaque bacteria, salivary
      components, and specific types of carious lesions. Protein, fat, and phosphorus
      in foods were all associated with inhibition of both sulcal and buccolingual
      (smooth-surface) caries. Food fluoride was associated with inhibition of
      buccolingual caries, whereas calcium was related to inhibition of sulcal caries.
      Glucose, reducing sugar, and sucrose in foods were all related to promotion of
      both sulcal and smooth-surface caries. The numbers of Streptococcus sobrinus in
      plaque were associated with promotion of smooth-surface caries only, whereas
      lactobacilli, non-mutans bacteria, and total viable flora were related to
      promotion of both smooth-surface and sulcal caries. The salivary flow rate was
      associated with inhibition of both buccolingual and sulcal caries. Salivary
      buffering capacity (at pH 7) and salivary lysozyme delivery were associated with
      inhibition of number and severity of sulcal caries, while the salivary amylase
      content was related to the promotion of the number of sulcal lesions.

PMID- 7512448
TI  - [Investigation on anti-HCV antibody in Shashi District].
AB  - In Shashi District, 2084 blood donors and 890 patients with liver diseases have
      been tested for anti-HCV antibody by using the second generation reagent. As a
      result, the blood donors showed a positive rate of 0.29% and the patients with
      liver diseases 1.35%. This indicated that HCV virus infection was present in
      Shashi District, and the infection is relatively low. Positive result was not
      found among 432 patients with hepatitis A and 8 patients with acute hepatitis B,
      while 11 out of 443 patients with chronic hepatitis B showed positive result with
      a positive rate of 2.48%. One of five patients with active cirrhosis of liver was
      positive for anti-HCV antibody. It indicates that the mixed or cross HCV
      infection might lead to chronicity of the HCV infection and active cirrhosis.

PMID- 7512449
TI  - [The study on clinical characteristics of the development of primary hepatocyte
      carcinoma induced by hepatitis B].
AB  - This article reports the clinical characteristics of 38 cases of patients with
      hepatitis B (HB) which developed into primary hepatocyte carcinoma (PHC), during
      a period of observation for 2-28 years (average 11.4 years). These patients were
      admitted repeatedly for 2 to 12 times (average 3.4 times). The clinical
      characteristics of the development of the symptoms in these patients were as
      follows: 1. Liver function fluctuated again and again. Ninety percent of these
      patients with HB developed liver cirrhosis (LC). Subsequently they developed into
      PHC. 2. HBV markers were positive over a long period of observation. During the
      phases of LC and PHC the rates of positive anti-HBe were 23.5% and 54.5%,
      respectively (P < 0.05). Comparing with anti-HBe, the rate of positive HBeAg was
      lower. 3. During the phase of HB, 21.0% of these patients had elevated alpha FP
      (mean titer 80.0 ng/ml). During the phase of PHC, 65.8% of the patients had
      abnormal alpha FP (mean titer 635.9 ng/ml) (P < 0.01). Sustained high level of
      gamma-GT and the ratio of gamma-GT/ALT higher than 1.5 were dangerous signals (P
      < 0.05). The level of ALP in these patients with HB was below 170 u/L. But 50% of
      them had high level of ALP when they developed into PHC. During the phase of LC
      these patients were detected regularly with ultrasonic waves.

PMID- 7512450
TI  - The nuclear tyrosine kinase c-Abl negatively regulates cell growth.
AB  - c-Abl is a tyrosine kinase localized primarily in the nucleus. Previous assays
      for abl function rely on cellular transformation by abl mutants, which are
      cytoplasmic. Using a conditional overexpression strategy, we have developed a
      functional assay for c-abl. Overexpression of c-abl inhibits growth by causing
      cell cycle arrest. Growth suppression requires tyrosine kinase activity, nuclear
      localization, and an intact SH2 domain. Overexpression of dominant negative c-abl
      disrupts cell cycle control and enhances transformation by tyrosine kinases, G
      proteins, and transcription factor oncogenes. These findings suggest that c-abl
      acts as a negative regulator of cell growth. This growth suppressive activity is
      functionally similar to that of tumor suppressor genes such as p53 and Rb.

PMID- 7512452
TI  - Blockade of cardiac inflammation in Mg2+ deficiency by substance P receptor
      inhibition.
AB  - In previous work we reported the elevation of circulating inflammatory cytokines
      in rodents maintained on a Mg(2+)-deficient diet. Within the first week of Mg2+
      deficiency, significant elevation of the neuropeptides substance P (SP) and
      calcitonin gene-related peptide (CGRP) occurs. The present study was designed to
      assess the effects of SP receptor blockade by CP-96,945 and its inactive
      enantiomer CP-96,344 on tissue cytokine levels and in vivo oxidative indexes. CP
      96,345 had no significant effect on circulating levels of SP or CGRP; however, at
      the tissue level, a significant decrease (P < .01) in myocardial accumulation of
      SP occurred; the inactive enantiomer was only slightly effective. In addition, CP
      96,345 significantly reduced (by 53%) the accumulation of tumor necrosis factor
      alpha (TNF-alpha) (but not interleukin-1 and interleukin-6) within the lesions;
      the effect of the enantiomer was insignificant. We conclude that treatment with
      CP-96,345 inhibits SP and TNF-alpha tissue levels in cardiac lesions, indicating
      a linkage between this neuropeptide and TNF-alpha. Both SP and TNF-alpha can
      trigger free radical production; plasma thiobarbituric acid-reactive materials
      were elevated 2.5-fold and red blood cell reduced glutathione was reduced 55%
      during Mg2+ deficiency. In the presence of CP-96,345, both indexes of in vivo
      oxidation were significantly attenuated; the enantiomer was ineffective. These
      latter observations point to a neuropeptide/TNF-alpha/free radical-triggered
      mechanism that may be the major pathway of systemic oxidative injury inducing the
      cardiomyopathic lesions seen during Mg2+ deficiency.

PMID- 7512453
TI  - Basement membrane of blood vessels during distraction osteogenesis.
AB  - A canine model of distraction osteogenesis has recently been developed that
      permitted the evaluation of bone formation and its vascularization during bifocal
      callotasis. In this model, the authors examined the composition of the blood
      vessels during distraction osteogenesis of the mandible for laminin and for Type
      IV collagen, both constituents of the vascular basement membrane. At the fibrous
      distraction site, at the juncture of the free cortical surface and the
      regenerated bone, and at the abutting cortical surfaces at the distal margin of
      the defect, laminin and Type IV collagen were present in all vessels.

PMID- 7512451
TI  - Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related
      transcription factor involved in the gp130-mediated signaling pathway.
AB  - Acute-phase response factor (APRF) is a transcription factor that binds to the
      interleukin-6 (IL-6)-responsive elements identified in the promoters of various
      acute-phase protein genes. We report here the purification and cloning of APRF.
      APRF exhibits a 52.5% overall homology at the amino acid level with p91, a
      component of the interferon (IFN)-stimulated gene factor 3 complexes. The cloned
      APRF protein is tyrosine phosphorylated and translocated into the nucleus in
      response to IL-6, but not in response to IFN-gamma. Tyrosine phosphorylation was
      also observed in response to other cytokines, such as leukemia inhibitory factor,
      oncostatin M, and ciliary neurotrophic factor, whose receptors share the IL-6
      receptor signal transducer gp130. In contrast, we observed that p91 is not
      tyrosine phosphorylated in response to IL-6. These results suggest that this
      novel p91-related protein may play a major role in the gp130-mediated signaling
      pathway and that selective activation of p91-related factors may explain the
      diversity of cellular responses to different cytokines.

PMID- 7512454
TI  - [Histological and radiobiological study on adult cases with ataxia
      telangiectasia].
AB  - Ataxia telangiectasia (AT) is a hereditary disease that involves both the immune
      and nervous system; its pathogenesis is believed to be due to disturbances in DNA
      repair system. Because children are usually affected, reports concerning adult
      patients are rare. In the present study, we performed comprehensive clinical,
      histological, and radiobiological examinations on two adult female siblings,
      currently 23 and 19 years old. The initial symptom was an ataxic gait, which
      began in the elder sister at the age of 20 and the younger sister at the age of
      18. Both had mild telangiectasia in the bulbar conjunctiva and auricula. The
      neurological manifestations of both were gaze nystagmus, cerebellar ataxia,
      hyporeflexia, and vibratory sensation disturbance. Only the elder sister showed
      stocking type sensory disturbance. The MRI of both patients revealed cerebellar
      atrophy, especially in vermis. After either X-ray irradiation or bleomycin
      treatment, fibroblast survival curve showed a marked, dose-dependent declined in
      both patients compared with normal controls. Similar patterns were observed in
      both patients. After bleomycin treatment, no differences in the survival ratio of
      cultured fibroblasts could be found between these adult patients and those
      observed in younger children with classic AT. Biopsied sural nerves showed a
      decrease in the number of large myelinated fibers, with a few myelinated axons
      having relatively thin myelin. There were severe atrophic changes, with
      regenerative myelinated fibers in the elder sister. In conclusion, both adult
      patients with delayed onset AT displayed similar bleomycin hypersensitivity in
      fibroblasts as would be expected in children with AT. Radiobiological
      examinations and sural nerve biopsy suggest that both disturbed cellular
      regeneration and atrophic process may play a role in the neural involvement in
      this disease.

PMID- 7512455
TI  - Modulation of the effect of atrial natriuretic peptide in human and bovine
      bronchi by phosphoramidon.
AB  - 1. We have previously shown that atrial natriuretic peptide causes
      bronchodilatation and reduces bronchial reactivity when administered
      intravenously or by inhalation to asthmatic patients. We wished to determine the
      direct effect of exogenously applied atrial natriuretic peptide on isolated
      airway and the role of proteases important in atrial natriuretic peptide
      degradation in other organ systems. 2. The ability of atrial natriuretic peptide
      (alpha-human atrial natriuretic peptide 28-amino acid) to relax precontracted
      tissues and to protect against methacholine-induced contraction was studied in
      human and bovine tissue. The role of neutral endopeptidase-24.11 and other
      proteases in regulating the effect of atrial natriuretic peptide on bronchial
      smooth muscle was also examined by studying the influence of phosphoramidon, a
      protease inhibitor, whose actions include the inhibition of neutral endopeptidase
      24.11, and the protease inhibitors leupeptin, aprotinin and soybean trypsin
      inhibitor on the airway response to atrial natriuretic peptide. 3. In human and
      bovine tissue atrial natriuretic peptide (10(-6) mol/l) caused a slight
      relaxation of methacholine-contracted tissue [mean (SEM) percentage inhibition of
      contraction of 13.2 (3.02)% and 9.41 (2.63)% respectively] and evoked a
      significant rightward shift of the cumulative concentration-response curve to
      methacholine [pD2 5.15 (0.23) and 4.85 (0.1) compared with control values of 6.14
      (0.1) and 5.85 (0.16), respectively]. 4. Phosphoramidon potentiated atrial
      natriuretic peptide-induced relaxation of methacholine-induced tone and the
      ability of atrial natriuretic peptide to protect against methacholine-induced
      contraction. The combination of leupeptine, aprotinin and soybean trypsin
      inhibitor did not significantly alter the bronchial response to atrial
      natriuretic peptide in either human or bovine tissues.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7512456
TI  - Mercurochrome allergy: concurrence of 2 hypersensitivity mechanisms in the same
      patient.

PMID- 7512457
TI  - [A clinical study on the effect of non-adrenergic non-cholinergic nerves in
      asthma].
AB  - Non-adrenergic non-cholinergic (NANC) nerves are the third nervous system in the
      lung. There are increasing evidences that the main transmitters of NANC
      inhibitory (NANC-i) nerves and NANC excitatory (NANC-e) nerves are vasoactive
      intestinal peptide (VIP) and substance P (SP) respectively. We measured the
      levels of plasma VIP. SP and bronchial responsiveness in the patients with
      asthma. Chronic bronchitis and healthy subjects. The results showed that VIP
      level is decreased and negatively correlated with airway resistance, whereas SP
      level is increased and positively correlated with bronchial hyperresponsiveness
      (BHR) in asthma. It is suggested that overexcitation of NANC-e nerves and
      deficiency of NANC-i nerves are closely related with asthma attack and BHR.

PMID- 7512458
TI  - [Limitation on the detection of serum antibody to hepatitis C virus].

PMID- 7512459
TI  - Morphological appearances of human lens epithelial cells in culture.
AB  - A system for culturing human lens epithelial cells in the laboratory was
      developed. The morphological appearances of the cells was studied using phase
      contrast, scanning and transmission electron microscopy. Cell marker studies
      using monoclonal antibodies to cytokeratin, vimentin and epithelial membrane
      antigen were also performed. There was a marked increase in cell size as a
      function of time in culture. After 3 to 4 weeks cells showed early signs of
      ageing. By 6 to 8 weeks the majority of the cells had become very irregular in
      shape and demonstrated irregularities of the plasma membrane and intra
      cytoplasmic vacuole formation. The cells stained strongly for vimentin and
      epithelial membrane antigen. Staining with cytokeratin was somewhat weaker. This
      culture technique provides us with a suitable model for studying the growth
      behavior of these cells.

PMID- 7512461
TI  - New Challenges in the Treatment of Hypertension, The Global Approach. Proceedings
      of the 2nd International Mediterranean Symposium on Hypertension. Lisbon,
      Portugal, 25-28 March 1993.

PMID- 7512460
TI  - [Granulocyte colony-stimulating factor (G-CSF) in the early stage of thyrostatic
      induced agranulocytosis].
AB  - After coronary angiography a 66-year-old man developed manifest hyperthyroidism
      (fT3 8.7 pg/ml, fT4 3.7 ng/dl) marked by tremor, restlessness and sweating. The
      hyperthyroidism was controlled by high dosages of thiamazole (240 mg daily) and
      lithium (24-36 mmol daily). But the white cell count dropped from
      8,000/microliters to 4,900/microliters on the eighth day. Although the thiamazole
      dose was reduced to 40 mg daily, the granulocytopenia became more severe and, on
      the 24th day of treatment, agranulocytosis occurred (neutrophilic granulocyte
      count 200/microliters), although the thiamazole had been discontinued. The
      patient was then isolated and treated prophylactically with ofloxacin.
      Simultaneously he received 5 micrograms/kg granulocyte-colony stimulating factor
      (G-CSF) subcutaneously daily for 7 days. On the sixth day of this treatment the
      granulocyte count was 520/microliters, next day 3,800/microliters, and after a
      further 2 days it overshot to 31,000/microliters, then gradually returning to
      normal values. -It is recommended that the use of G-CSF should be considered also
      for thyrostatic-induced agranulocytosis, because it may shorten this dangerous
      phase.

PMID- 7512462
TI  - Effects of calcium antagonists on adrenaline-induced hypokalaemia.
AB  - Long term treatment with nifedipine and nitrendipine, but not verapamil and
      diltiazem, may reduce plasma potassium levels in hypertensive patients. To test
      the hypothesis that this effect is related to adrenaline-mediated influx of
      potassium from the extracellular space, the effect of adrenaline infusions (12.5,
      25 and 50 ng/kg/min) on plasma potassium levels was assessed in normotensive
      subjects after administration of placebo for 4 days, and after administration of
      nitrendipine, verapamil or diltiazem for 4 days. The adrenaline-induced decrease
      in plasma potassium levels was enhanced in subjects receiving nitrendipine, but
      was unaffected in those subjects receiving verapamil or diltiazem. The effects of
      adrenaline on blood glucose levels, heart rate and blood pressure were
      uninfluenced in subjects receiving nitrendipine or verapamil, and were blunted in
      subjects receiving diltiazem. These results suggest that enhancement of the
      adrenaline-induced intracellular transfer of potassium from the extracellular
      space is relatively specific to dihydropyridine calcium antagonists.

PMID- 7512463
TI  - The kidney and arterial hypertension.
AB  - It has been known for some time that a relationship exists between the kidney and
      blood pressure. The renal origin of arterial hypertension has been demonstrated
      in different animal models resembling human hypertension, with data from humans
      seeming to confirm this hypothesis. On the other hand, the renal vasculature also
      suffers the consequences of arterial hypertension, and renal insufficiency can
      develop as a result of elevated blood pressure levels. Antihypertensive therapy
      can prevent the development of renal damage secondary to hypertension. For
      example, calcium antagonists possess specific renal effects that not only
      facilitate their antihypertensive capacity but also protect the kidney from the
      development of renal failure.

PMID- 7512464
TI  - Long term effects of sustained release verapamil on the renal and systemic
      haemodynamic parameters in hypertensive patients with mild to severe chronic
      renal failure.
AB  - Calcium antagonists such as verapamil are among the antihypertensive agents
      categorised as first line treatments for essential hypertension. They have also
      shown efficacy in secondary forms of hypertension, including hypertension
      associated with chronic renal failure, irrespective of the degree of renal
      impairment. Systemic and renal haemodynamic parameters, and renal function were
      analysed in 15 hypertensive patients with mild to severe chronic renal failure
      after a 2-week placebo period and after 4 weeks of administration of verapamil
      sustained release (SR) 240 mg/day. After 4 weeks of treatment with verapamil SR,
      blood pressure was normalised in all patients. Arterial pressure decreased as a
      result of the decrease in systemic vascular resistance, while cardiac output and
      heart rate remained unchanged. Verapamil therapy did not significantly affect
      left cardiac function curves. The normalisation of arterial pressure did not
      result in changes in the glomerular filtration rate; however, renal vascular
      resistance decreased significantly, although the filtration fraction remained
      unchanged. Renal blood flow increased significantly and there was a significant
      increase in uricosuria and a subsequent decrease in plasma uric acid levels. In
      conclusion, verapamil SR is an effective and well tolerated treatment for
      hypertension associated with chronic renal failure.

PMID- 7512465
TI  - Calcium antagonists and ACE inhibitors. Effect on endothelium and vascular smooth
      muscle.
AB  - The effects of cardiovascular drugs on endothelium and vascular smooth muscle
      function are important for the prevention of cardiovascular disease. Changes in
      endothelial function are an early event in most forms of cardiovascular disease
      and, later in the disease process, vascular smooth muscle cells are functionally
      altered and begin to migrate to and proliferate in the intima. Calcium
      antagonists and angiotensin converting enzyme (ACE) inhibitors are widely used in
      patients with cardiovascular disease and are thought to have vascular protective
      effects. ACE, an enzyme located in the endothelial cell membrane, activates
      angiotensin I and angiotensin II, and deactivates bradykinin. Bradykinin
      activates endothelial bradykinin (B2) receptors, which results in the formation
      of nitric oxide and prostacyclin. Hence, ACE inhibitors not only prevent the
      formation of angiotensin II, but also increase the local levels of bradykinin and
      in turn nitric oxide and prostacyclin. These compounds are vasodilators and
      potent inhibitors of platelet function, and therefore may mediate important
      protective effects of ACE inhibitors. Furthermore, nitric oxide may have
      antiproliferative effects in vascular smooth muscle cells. Calcium antagonists do
      not appear to affect the release of endothelium-derived relaxing factors or any
      other endothelial product. However, they facilitate endothelium-dependent
      relaxation and reduce the contracting effects of endothelin-1 at the level of
      smooth muscle. Indeed, in some blood vessels, e.g. the large coronary arteries
      and the human forearm circulation, verapamil and nifedipine antagonise endothelin
      induced contractions. In addition, calcium antagonists inhibit the effects of
      platelet-derived growth factor and may have antiproliferative effects in vascular
      smooth muscle cells. In conditions involving progressive dysfunction of the
      endothelium, vascular deposition of platelets increases the local levels of
      platelet-derived growth factor, and the antiproliferative effects of calcium
      antagonists may thus be particularly important.

PMID- 7512466
TI  - Stress response and antihypertensive treatment.
AB  - Results from many studies suggest that the central nervous system may play an
      important role in enhancing and maintaining sympathetic, metabolic and
      haemodynamic effects in patients with hypertension. Likewise, emotional and
      mental stresses may provoke phasic and sustained adrenergic responses in
      normotensive and untreated hypertensive patients. Because the various
      antihypertensive medications have different mechanisms of action, and elicit
      different neurovegetative responses, it is useful to distinguish between the
      effects of different treatments on sympathetic activity. To identify the effect
      of stress on sympathetic reactivity, we evaluated the extracardiovascular and
      haemodynamic responses to various stressor agents using noninvasive techniques.
      This psychophysiological approach allowed us to standardise stress, to identify
      individual cardioneurovegetative responses both before and during treatment, and
      to establish the effects of various treatments on the cardioneurovegetative
      response. The extracardiovascular psychophysiological response of patients with a
      family history of hypertension and of normotensive patients who later became
      hypertensive was characterised by an inability to recover after mental challenge.
      Therefore, prolonged sympathetic activity resulting from mental stimulation may
      contribute to the development of hypertension. Antihypertensive medications
      affected sympathetic reactivity differently. For example, nifedipine worsened
      sympathetic reactivity, while verapamil was able to correct abnormal
      neuroadrenergic responses. Furthermore, verapamil was successfully combined with
      enalapril in patients whose hypertension was resistant to monotherapy with the
      angiotensin converting enzyme (ACE) inhibitor. Therefore, the functional and
      structural consequences of sympathetic stimulation resulting from daily
      activation and pharmacological blood pressure adjustments are important in
      hypertensive patients, because they may have abnormal sympathetic reactivity to
      various stimuli.

PMID- 7512467
TI  - Individualised selection of antihypertensive therapy.
AB  - Theoretically, it should be possible to match the requirements of individual
      patients with the pharmacological and clinical properties of the large number of
      antihypertensive drugs now available. The concept of automatic sequential stepped
      care therapy is now largely outdated, but therapy of clinically important
      hypertension must be initiated with one agent. Diuretics remain a first-line
      option in the elderly and in Black patients, as do calcium antagonists. Outcome
      trials are available only for the elderly, and in these the benefits of initial
      diuretic therapy are well documented. Nonetheless, diuretics may often need to be
      co-prescribed with a beta-blocker or an adrenergic modifier such as methyldopa.
      beta-Blockers are preferred in patients with ischaemic heart disease or enhanced
      adrenergic drive, while alpha-blockers are preferred in patients with blood lipid
      abnormalities or prostatic problems. Calcium antagonists or angiotensin
      converting enzyme (ACE) inhibitors are being increasingly used as initial therapy
      when quality of life is important and metabolic neutrality is required. Calcium
      antagonists are more likely to be effective first-line therapy than ACE
      inhibitors in patients with a high salt intake, in patients with Raynaud's
      disease, when angina pectoris is present, and in Black patients. ACE inhibitors
      are preferred for combination with diuretic agents, and in the presence of
      congestive heart failure or low salt intake. Experimentally, both calcium
      antagonists and ACE inhibitors can prevent ischaemic ventricular fibrillation and
      atheroma. Combination therapy between these 2 drug classes is gaining increasing
      acceptance because of these theoretical advantages.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7512469
TI  - Lipid profile during antihypertensive treatment. The SLIP Study Group. Study on
      Lipids with Isoptin Press.
AB  - Some antihypertensive drugs adversely affect the plasma lipid profile, and this
      has to be taken into account when choosing treatment for hypertension because it
      may offset the beneficial blood pressure-lowering effect of these agents. In this
      study, the long term effects of verapamil sustained release (SR) 240mg daily and
      enalapril 20mg daily on plasma lipid levels were investigated in 931 patients
      with mild to moderate hypertension. Patients whose blood pressure was not
      effectively lowered after at least 1 month of monotherapy had either enalapril
      20mg once daily added to their verapamil treatment or hydrochlorothiazide 12.5mg
      once daily added to their enalapril treatment. Blood pressure and lipid profile
      were assessed before and after 6 months of treatment. Of 864 evaluable patients,
      563 patients (65.1%) were successfully treated with monotherapy and 220 patients
      (25.5%) required combination therapy. A total of 81 patients withdrew from the
      trial. Systolic and diastolic blood pressure were significantly reduced by
      treatment with either verapamil or enalapril, and heart rate was reduced
      slightly, but significantly, by both treatments. Total cholesterol, triglycerides
      and low density lipoprotein were significantly reduced by both treatments. High
      density lipoprotein levels were significantly increased in verapamil recipients,
      but not in enalapril recipients. Adverse effects occurred in 37 (3.9%) patients
      receiving verapamil SR and 25 (2.7%) patients receiving enalapril. In conclusion,
      long term treatment with the antihypertensive agents verapamil and enalapril,
      alone or in combination regimens, significantly improved the plasma lipid
      profile. Verapamil SR had the most beneficial effect on plasma lipid levels.

PMID- 7512468
TI  - The inter-relationship between insulin resistance and hypertension.
AB  - Insulin resistance and compensatory hyperinsulinaemia commonly occur in patients
      with untreated essential hypertension. The coexistence of insulin resistance and
      hypertension can be viewed as a cause-effect relationship (insulin resistance as
      a cause of hypertension or vice versa) or as a noncausal association. Insulin can
      increase blood pressure via several mechanisms: increased renal sodium
      reabsorption, activation of the sympathetic nervous system, alteration of
      transmembrane ion transport, and hypertrophy of resistance vessels. Conversely,
      hypertension can cause insulin resistance by altering the delivery of insulin and
      glucose to skeletal muscle cells, resulting in impaired glucose uptake. For
      example, hypertension can impair vasodilation of skeletal muscle as a result of
      vascular structural changes and rarefaction, and increased response to
      vasoconstrictor stimuli. Also, the prevalence of muscle type 2b fibres (fast
      twitch fibres) may contribute to the development of insulin resistance. The
      common pathogenetic mechanism for both insulin resistance and hypertension could
      be activation of the sympathetic nervous system. This results in
      vasoconstriction, and may contribute to the genesis of vascular structural
      changes and increase the number of fast twitch fibres. Finally, hypertension and
      insulin resistance can be viewed as a noncausal association, according to the
      following hypotheses: 1) they may represent 2 independent consequences of the
      same metabolic disorder (intracellular free calcium accumulation), or 2) insulin
      resistance is a genetic marker and/or a pathogenetic mechanism of multiple
      metabolic abnormalities frequently associated with hypertension.

PMID- 7512470
TI  - Epidemiology of high blood pressure and obesity.
AB  - The relationship between bodyweight and arterial pressure was first discovered
      early this century. More recently, epidemiological studies have confirmed the
      correlation between bodyweight and blood pressure in both adults and children.
      Serum cholesterol levels, blood glucose levels, uric acid levels and blood
      pressure increase with increasing bodyweight. In the presence of androgens, upper
      body obesity, caused by excessive intake of calories, increases cardiovascular
      risk factors, probably as a result of hyperinsulinaemia. The activity of Na+/K(+)
      ATPase in the cells of obese subjects is reduced in a way that may be genetically
      determined, or may be mediated by changes in plasma insulin levels or a natural
      inhibitor of Na+/K(+)-ATPase. In vitro studies have shown that the potency of a
      non-ouabain inhibitor of Na+/K(+)-ATPase is enhanced by the presence of insulin.
      This may result in vascular smooth muscle having increased reactivity to pressor
      agents. A knowledge of cellular membrane transport may lead to a better
      understanding of the epidemiology of obesity-related hypertension.

PMID- 7512471
TI  - Diagnosis of insulin resistance.
AB  - Soon after the discovery of insulin, the importance of insulin sensitivity
      assessment was recognised. Recently, the role of insulin resistance in
      cardiovascular morbidity and mortality has been widely accepted and many methods
      for in vivo assessment of insulin resistance have been developed. They may be
      classified as 'closed-loop' techniques (in which insulin and glucose
      concentrations are allowed to interact freely), 'open-loop' techniques (in which
      insulin and/or glucose levels are fixed) and 'model methods' (which use a
      mathematical model to analyse the interactions between insulin secretion patterns
      and glucose disposal). Although there is no ideal method available to date, open
      loop techniques avoid many of the difficulties involved in the interpretation of
      closed-loop or model methods, and are preferred by most investigators. The
      glucose clamp technique is recognised as the 'gold standard' for assessment of
      insulin sensitivity; however, the insulin suppression test is adequate in most
      circumstances and is much simpler to perform.

PMID- 7512472
TI  - Trandolapril. How does it differ from other angiotensin converting enzyme
      inhibitors?
AB  - Among the physicochemical, pharmacokinetic and pharmacodynamic properties that
      differentiate trandolapril from other angiotensin converting enzyme (ACE)
      inhibitors, the most clinically relevant ones are those that contribute to the
      long duration of action of the drug. The long elimination half-life of
      trandolapril and its strong lipophilicity, high ACE inhibitor potency and high
      affinity for the ACE cause the drug to have a long biological half-life. The long
      duration of action of trandolapril may be demonstrated experimentally; near total
      ACE inhibition is observed 24 hours after single dose administration and there is
      significant ACE inhibition 72 hours following drug withdrawal after long term
      therapy. We have analysed the duration of blood pressure lowering during long
      term therapy with commercially available ACE inhibitors in published studies
      using ambulatory blood pressure monitoring. On the basis of results from 19
      studies undertaken in patients with mild to moderate hypertension, it was
      possible to reconstruct the curve of the magnitude of blood pressure changes
      against time. Mean trough: peak ratio calculations showed that once-daily
      administration produced ratios higher than 50% with enalapril (40 to 80%),
      lisinopril (40 to 70%) and trandolapril (50 to 100%). Other ACE inhibitors had
      trough: peak ratios lower than 50%. Despite many methodological limitations, this
      literature analysis demonstrates that trandolapril has a blood pressure-lowering
      effect for the full 24-hour period. Studies in which a dose is occasionally
      omitted show that the blood pressure-lowering effect of trandolapril may last
      beyond 24 hours.

PMID- 7512473
TI  - Hypertension and insulin resistance. Glycaemia and insulinaemia in overweight
      hypertensive patients.
AB  - The relationship between insulin resistance and hyperinsulinaemia on one hand and
      hypertension on the other hand has become apparent during the last few years.
      Insulin resistance, which may be genetically determined, is, according to our
      present understanding, the 'key player' in the metabolic syndrome. However, the
      pathophysiology of the combination of factors has not yet been fully elucidated.
      Early therapeutic intervention for insulin resistance, hyperinsulinaemia and
      hypertension may prevent the clinical manifestation of non-insulin-dependent
      (type 2) diabetes. Preliminary results of an ongoing study investigating the
      effects of trandolapril or the diuretic combination of hydrochlorothiazide and
      triamterene on serum glucose and insulin levels are presented.

PMID- 7512474
TI  - Nephroprotective effect of ACE inhibitors.
AB  - In most cases of renal disease, progression of renal failure occurs via
      nonspecific mechanisms that can be dissociated from the primary cause of renal
      damage. Progression of disease is accompanied by glomerulosclerosis and
      tubulointerstitial fibrosis. Loss of autoregulation and afferent renal
      vasodilation renders the glomerular microcirculation particularly susceptible to
      systemic hypertension. Glomerular growth is an ancillary factor permitting the
      development of glomerulosclerosis. Experimental and clinical studies indicate
      that angiotensin converting enzyme (ACE) inhibitors may prevent progressive renal
      deterioration. Furthermore, it appears that this effect can be dissociated, at
      least in part, from the haemodynamic effects of ACE inhibitors. Some evidence
      indicates that the renal-protective effects of ACE inhibitors results from their
      effects on glomerular growth and glomerular permselectivity. The role of reduced
      generation of angiotensin II or accumulation of kinins in the renal effects of
      ACE inhibitors is under investigation. Prospective clinical trials have
      demonstrated that ACE inhibitors reduce proteinuria and interfere with
      progression of renal disease to a greater degree than can be explained by their
      blood pressure lowering effects alone.

PMID- 7512476
TI  - New aspects of antihypertensive treatment. Metabolism, the kidney and the heart.
AB  - This paper briefly reviews recent evidence concerning the relationship between
      hypertension and alterations in glucose and lipid metabolism and renal and
      cardiac damage. It is now clear that high blood pressure is frequently associated
      with insulin resistance and dyslipidaemia. This suggests a possible pathogenetic
      link between hypertension and deranged metabolism. It also suggests, however,
      that the hypertensive patient is likely to have other cardiovascular risk factors
      in addition to hypertension. It is also clear that lowering blood pressure may
      not only reduce the overall cardiovascular risk but may be specifically nephro-
      and cardioprotective. However, it is difficult to assess the effect of
      antihypertensive treatment in these areas, because there are no simple and
      sensitive measures of the progression of renal disease, and antihypertensive
      therapy does not provide consistent protection against coronary heart disease.
      Furthermore, the degree of protection obtained is less than would be expected on
      the basis of epidemiological evidence. Further trials are needed to fully resolve
      these issues.

PMID- 7512475
TI  - The pathogenesis of hypertension in obese subjects.
AB  - Obese subjects are at an increased risk of becoming hypertensive and vice versa.
      Essential hypertension and obesity are commonly accompanied by insulin resistance
      (defined as impaired insulin-mediated glucose disposal) and hyperinsulinaemia. In
      the offspring of patients with essential hypertension, insulin resistance and
      hyperinsulinaemia, as well as related increases in serum low density lipoproteins
      and triglycerides, often occur prior to the development of essential
      hypertension, overweight or central redistribution of body fat. Moreover, once
      obesity, and in particular central obesity, is present, insulin resistance is
      more marked in hypertensive than in normotensive obese subjects.
      Hyperinsulinaemia and/or insulin resistance in turn promote body fat deposition
      and impaired glucose tolerance. This cycle helps to explain why a familial
      predisposition to essential hypertension poses an increased risk of developing
      not only hypertension but also dyslipidaemia, obesity and non-insulin-dependent
      (type 2) diabetes. It is still unclear whether insulin resistance and/or
      hyperinsulinaemia also promote hypertension per se. Regardless of insulin's exact
      pathogenic role, obesity and/or a high dietary intake of carbohydrates, salt,
      etc. can induce several potential pressor mechanisms: 1) higher plasma
      noradrenaline (norepinephrine) and adrenaline (epinephrine) levels, suggesting a
      higher sympathetic tone in obese than in nonobese subjects, and in hypertensive
      obese than in normotensive obese subjects; 2) similarly, a tendency to
      hyperaldosteronism, with largely normal plasma renin activity, in obese
      hypertensive patients; 3) enhanced sensitivity of blood pressure to salt; 4)
      increased total blood volume (although it is normal relative to body surface
      area), leading to increased cardiac output and eventually eccentric left
      ventricular hypertrophy; and 5) increased cytosolic free Ca++ levels and reduced
      intracellular Mg++ levels in the blood cells of obese hypertensive patients and
      patients with non-insulin-dependent diabetes, although this finding cannot
      necessarily be extrapolated to cationic levels in vascular muscle cells. Total
      peripheral vascular resistance is usually low in normotensive obese subjects and
      rises with the development of hypertension; compared with lean patients with
      essential hypertension, obese hypertensive patients tend to have a slightly lower
      level of total peripheral vasoconstriction and a slightly higher cardiac output.
      Considering the intimate association between essential hypertension and obesity,
      as well as the prevalence and prognostic relevance of this combination, the
      spectrum of accompanying metabolic and cardiovascular abnormalities deserves
      careful consideration in the evaluation of therapeutic care for such patients.

PMID- 7512478
TI  - The pathophysiology of hypertension. Differences between young and elderly
      patients.
AB  - While structural and functional signs of a genetic predisposition to hypertension
      may sometimes be detected in the juvenile cardiovascular system, the borderline
      phase characteristic of young hypertensive patients is often dominated by a
      'hyperkinetic' circulatory state. The modest pressure elevation is then mainly
      due to an increase in cardiac output and accentuated responses to neurohormonal
      stimuli. During the development of established hypertension, cardiac output
      gradually returns to normal and the high pressure state is largely a result of
      chronically elevated systemic resistance with cardiovascular 'structural upward
      resetting'. Signs of increased neurohormonal influences usually become less
      prominent. In general, the chronic high pressure state tends to accelerate
      ordinary cardiovascular aging, and therefore the advanced stages of primary
      hypertension are characterised by considerable interstitial infiltration with
      consequent wall stiffening and reduced aortic 'Windkessel' function. This further
      enhances the end-systolic afterload for the left ventricle, while at the same
      time myocardial strength and coronary reserve tend to decline. Age-related
      reductions in barostat function, reflex efficiency, and renal excretory capacity
      are also accentuated, and endothelial function suffers. Thus, the cardiovascular
      system in elderly hypertensive patients is generally characterised by pronounced
      and apparently poorly reversible structural changes. Nevertheless, recent studies
      indicate that even late phases of hypertension in elderly patients may respond
      favourably to treatment. This may predominantly reflect the high risk of serious
      cardiovascular damage in the elderly, but also that therapeutic intervention is
      able to reverse the structural changes observed in the advanced stages of
      hypertension.

PMID- 7512477
TI  - Treatment of hypertension in the elderly.
AB  - Since 1967, results from well controlled long term studies have provided
      convincing evidence of the benefit of antihypertensive therapy in middle-aged
      patients. However, many physicians have hesitated to apply these findings to
      patients over 60 years of age. Recently, the results of several prospective
      randomised long term trials investigating the treatment of hypertension in
      elderly patients have been published. An analysis of the results of 5 major
      trials shows that antihypertensive treatment reduces overall mortality by 20%,
      cardiovascular mortality by 33%, the incidence of fatal and nonfatal
      cerebrovascular events by 40%, and complications as a result of coronary heart
      disease (i.e. fatal and nonfatal myocardial infarction and sudden cardiac death)
      by 15%. On the basis of trials undertaken in elderly patients with either high
      systolic and diastolic blood pressure or isolated systolic hypertension,
      antihypertensive therapy was more beneficial, in absolute terms, in elderly
      patients than in middle-aged patients with mild hypertension. Treatment was
      withdrawn as a result of adverse effects in about 2% of middle-aged and elderly
      hypertensive patients per year. Therefore, it is clear that elderly hypertensive
      patients should be treated.

PMID- 7512480
TI  - General considerations when treating hypertension.
AB  - Numerous intervention studies have clearly demonstrated the value of
      antihypertensive treatment. By lowering diastolic blood pressure 5 to 6mm Hg in
      middle-aged hypertensive patients, a 42% reduction in stroke morbidity and a 14%
      reduction in coronary heart disease morbidity can be obtained. Recently published
      large intervention trials have shown that antihypertensive treatment provides
      even greater benefits in elderly hypertensive patients. Not only are
      cardiovascular morbidity and mortality reduced, but, in the 'old elderly', total
      mortality is reduced when blood pressure is lowered. It is conceivable that even
      better outcomes will be achieved with newer antihypertensive therapies, such as
      calcium antagonists and angiotensin converting enzyme inhibitors, and this
      possibility is being investigated in large prospective intervention trials.

PMID- 7512482
TI  - Cardiovascular benefits of antihypertensive therapy postacute myocardial
      infarction. Therapeutic considerations.
AB  - Patients who survive a myocardial infarction are at high risk of future recurrent
      infarction, sudden death and other vascular events. While it is possible to
      predict many risks, it is not possible to predict reinfarction. Since
      reinfarction carries a poor prognosis we should attempt to reduce this risk in
      all patients who survive an acute myocardial infarction. This paper reviews the
      wide range of lifestyle modifications and pharmacological interventions aimed at
      improving the long term prognosis of patients who have suffered an acute
      myocardial infarction.

PMID- 7512479
TI  - Influence of antihypertensive drugs on exercise capacity.
AB  - Both single dose and short term diuretic treatment adversely affect maximal
      exercise capacity and the duration of prolonged submaximal exercise. However,
      insufficient data are available to establish the effect of long term diuretic
      treatment on exercise capacity. beta-Blockade reduces maximal aerobic power by
      approximately 7%. In addition, the capacity for prolonged submaximal exercise
      appears to be markedly impaired in normotensive and hypertensive patients,
      particularly when nonselective beta-blockers are prescribed. Fewer data are
      available for other drugs, but, whatever the mechanism of vasodilation, drugs
      that reduce systemic vascular resistance do not seem to have any effect on
      exercise capacity.

PMID- 7512481
TI  - Pharmacological aspects of calcium antagonism. Short term and long term benefits.
AB  - Calcium antagonists are widely used in the management of a variety of
      cardiovascular disorders, including angina pectoris, myocardial infarction,
      atherosclerosis and hypertension. At the cellular level these drugs act primarily
      by limiting calcium ion (Ca++) entry through voltage-sensitive, Ca(++)-selective
      channels. This effect contributes to the antiatherogenic properties of calcium
      antagonists and is primarily responsible for their ability to reduce systolic and
      diastolic blood pressure, and to protect the myocardium. The cardioprotective
      effect of calcium antagonists is a complex phenomenon that needs to be considered
      in terms of the immediate consequences of Ca(++)-channel blockade and subsequent
      reduction in cytosolic Ca++, together with the long term benefits. These long
      term benefits include protection of the vasculature, an attenuation of
      hypertension-induced hypertrophy and improved left ventricular diastolic
      function. However, irrespective of whether it is the short or long term effects
      of calcium antagonists that are being considered, it is their ability to lower
      cytosolic Ca++ that is primarily responsible for their cardio- and vascular
      protective effects.

PMID- 7512483
TI  - Postinfarct treatment with verapamil. Effect of verapamil in patients with
      hypertension.
AB  - In the Danish Verapamil Infarction Trial II (DAVIT II), treatment with verapamil
      360 mg/day improved reinfarction-free survival compared with administration of
      placebo. Verapamil appears to effectively prevent reinfarction and sudden death,
      i.e. sudden events (hazard ratio 0.78 compared with placebo, 95% confidence
      limits 0.62 to 0.99). In a retrospective analysis of data from DAVIT II,
      verapamil treatment in patients with systemic hypertension prevented reinfarction
      significantly better than placebo (15 of 149 verapamil recipients compared with
      27 of 152 placebo recipients reinfarcted, p = 0.04). Similarly, first
      cardiovascular events, i.e. first reinfarction, first stroke or death, were
      prevented more effectively by verapamil treatment than by administration of
      placebo (29 verapamil recipients vs 42 placebo recipients had first
      cardiovascular events, p = 0.07).

PMID- 7512484
TI  - Hypertension and diastolic function.
AB  - Abnormalities in left ventricular (LV) diastolic function in the presence of
      normal LV systolic performance is one of the earliest cardiac manifestations of
      systemic hypertension. Alterations in diastolic filling indices have been
      observed more clearly in patients with LV hypertrophy, although it is evident
      that these filling abnormalities may be significantly influenced by age,
      bodyweight, blood pressure, left atrial size, LV systolic function, interstitial
      fibrosis, impaired coronary blood flow, and sympathetic stimulation. Several
      studies indicate that abnormal diastolic function may be responsible, at least in
      part, for an impaired LV systolic response to isotonic or isometric exercise,
      even when systolic performance is normal at rest. Short and long term
      administration of some antihypertensive drugs, such as angiotensin converting
      enzyme (ACE) inhibitors and calcium antagonists, particularly of the
      phenylalkylamine type, may significantly improve diastolic function. We observed
      that abnormal diastolic filling was significantly improved when LV mass was
      reduced by long term antihypertensive therapy. Even when treatment was withdrawn
      and blood pressure had increased again, LV mass remained reduced. These results
      suggest that regression of LV mass might improve LV diastolic function per se.
      Further studies are needed to assess the effect of improvement of LV diastolic
      function on the long term prognosis of patients with hypertension.

PMID- 7512485
TI  - Mechanical function and histological structure of the arterial wall. The response
      to antihypertensive treatment.
AB  - Alterations in the structure and function of large arteries could be a major
      factor in the mortality and morbidity of hypertensive patients. This paper
      summarises the effects of various pharmacological treatments on the mechanical
      (functional) properties of large arterial walls and on the structure and
      composition of these vessels. Firstly, during arterial hypertension, increases in
      arterial stiffness, associated with medial hypertrophy and/or hyperplasia and
      alterations in extracellular matrix, are always observed. Sodium intake and aging
      may influence the arterial wall properties, causing an increase in stiffness,
      independently of their effect on blood pressure. In parallel, administration of
      low doses of diuretics to hypertensive rats did not cause significant
      haemodynamic changes, but did cause an increase in arterial distensibility.
      Nitrates and derivatives have specific effects on the smooth muscle from large
      arteries in hypertensive patients. Significant increases in the diameter of large
      arteries and in arterial wall stiffness have been reported in clinical studies,
      but these effects have a short time constant. In humans and animals, angiotensin
      converting enzyme (ACE) inhibitors and calcium antagonists cause relaxation of
      arterial smooth muscle and, therefore, improve the functional component of the
      reduced distensibility observed in hypertension. Long term treatment with ACE
      inhibitors and calcium antagonists induces a significant reduction in medial
      hypertrophy. However, it is difficult to distinguish between the direct effects
      resulting from pressure reduction and a specific drug effect.

PMID- 7512486
TI  - Effect of verapamil on atherosclerosis.
AB  - Whether antihypertensive agents exert an antiatherosclerotic effect by blood
      pressure reduction or independently of their antihypertensive effect is
      clinically relevant. Animal studies have generally shown that the calcium
      antagonist verapamil has a preventive rather than a therapeutic
      antiatherosclerotic effect, which is independent of its antihypertensive effect.
      However, doses used in animal studies were much higher than those administered to
      humans and, in animals, the time of administration of verapamil coincided with
      the application of atherogenic stimulus. Human studies have given controversial
      results. Verapamil appears to effectively reduce the restenosis rate after
      coronary angioplasty. However, in patients with coronary stenosis who were
      undergoing bypass surgery, results were conflicting: a retrospective study
      provided positive results, while a prospective study gave negative results. An
      ongoing study investigating the effect of verapamil on the carotid arteries of
      hypertensive patients could help clarify the relationship between blood pressure
      reduction and the progression, regression or development of carotid lesions.

PMID- 7512487
TI  - Lowering blood pressure. How far, how fast?
AB  - There is a general consensus that high blood pressure (BP) must be lowered
      gradually. A reduction in BP beyond the limits of the autoregulatory curve may
      compromise perfusion of vital organs, resulting in organ ischaemia. However, a
      reduction in high BP offers protection against cerebral events, and some
      protection against coronary heart disease. The limited protection against
      coronary heart disease provided by BP reduction may be partially explained by the
      so-called 'J-shaped curve': a reduction in diastolic blood pressure below 85 mmHg
      may lead to a paradoxical increase in coronary events, although this effect is by
      no means well established. In addition, the incidence of several events
      associated with cardiovascular disease peaks during morning hours, at a time when
      some antihypertensive drugs are least effective. This may also explain the
      limited coronary protection achieved after administration of antihypertensive
      drugs.

PMID- 7512488
TI  - Arterial compliance and blood pressure.
AB  - As a result of the dual function of arteries, the conduit and cushioning
      functions, arterial pressure has 2 components: the steady component,
      characterised by mean blood pressure, and the pulsatile component, characterised
      by pulse pressure. Arterial compliance mostly depends on arterial intrinsic
      elastic properties, and is a determinant of the propagation speed of the pulse
      pressure wave. Decreased arterial compliance is responsible for both an increase
      in the incident pressure wave and the higher effect of reflected pressure waves.
      This increases systolic pressure and ventricular afterload, and generates left
      ventricular hypertrophy. Arterial structural changes that accompany the aging
      process result in a loss of distensibility and compliance. In essential as well
      as in secondary hypertension, arterial compliance is reduced, and age-related
      structural changes of the arterial wall are accelerated. Whether the change in
      arterial compliance is a passive consequence of the increase in blood pressure or
      is related to changes in the arterial wall structure remains unclear. Calcium
      antagonists improve the distensibility and compliance of large and small
      arteries, contributing significantly to the improvement in the management of
      essential and secondary hypertension.

PMID- 7512489
TI  - Effects of angiotensin converting enzyme inhibitors on left ventricular
      hypertrophy.
AB  - It is well known that, in patients with essential hypertension, left ventricular
      hypertrophy (LVH) is an independent risk factor for cardiovascular disease.
      However, it has been demonstrated that normalisation of arterial pressure, by
      therapy with antihypertensive drugs, is associated with regression of LVH,
      although the extent and time-course of this phenomenon depend on the
      antihypertensive drug used. In particular, angiotensin converting enzyme (ACE)
      inhibitors seem capable of inducing a faster and more complete reversal of LVH in
      patients with essential hypertension than other antihypertensive drugs. The
      mechanisms underlying this property of ACE inhibitors remain unclear, although 2
      features of ACE inhibitors may be particularly relevant. The first is their
      ability to improve large artery compliance, this being a major determinant of
      LVH. Arterial compliance is reduced in essential hypertension, resulting in
      increased left ventricular end-systolic stress, which then contributes to the
      development of LVH. The second possible mechanism by which ACE inhibitors reverse
      LVH to a greater degree than other antihypertensive drugs may relate to their
      ability to interfere with the cardiopulmonary receptor control of the
      circulation. Thus, ACE inhibitors may counteract the neural and hormonal
      abnormalities that contribute to the maintenance of LVH in hypertensive patients.

PMID- 7512491
TI  - Structural conservation and functional diversity--profile of a political peptide.

PMID- 7512490
TI  - White coat hypertension and related phenomena. A clinical approach.
AB  - In this paper, several clinical problems associated with the diagnosis of
      hypertension are discussed. Blood pressure variability and reactivity are factors
      underlying the difficulties in the diagnosis of hypertension. These phenomena are
      interrelated and mixed. White coat hypertension (WCH), referring to the
      phenomenon of a high diastolic pressure at the doctor's office and a normal
      diurnal diastolic pressure when it is measured by ambulatory monitoring, is the
      most important clinical problem of diagnosis. Blood pressure variability is
      described, since it is essential to understand changes in pressure throughout the
      day, and its phasic and tonic components. Blood pressure differences between
      activity and rest, usually seen as daytime/night-time differences, allow for
      blood pressure control in most patients with moderate hypertension. Prevalence of
      WCH depends on the cut-off point used by the investigators for normal diurnal
      blood pressure; thus, between 53% and 12% of patients may have WCH. In our
      studies, a prevalence of 35% has been found. The alert reaction, labile and
      borderline hypertension and WCH result from a mix of both variability and
      reactivity, and patients with these conditions are at a higher cardiovascular
      risk than normotensive controls. Ambulatory blood pressure monitoring, which
      enables true hypertensives to be distinguished from false hypertensives, is the
      most useful technique available to date for the diagnosis of hypertension.

PMID- 7512494
TI  - Galanin gene expression is increased in the anterior pituitary gland of the human
      growth hormone-releasing hormone transgenic mouse.
AB  - The peptide galanin is synthesized within and secreted from specific cells of the
      anterior pituitary gland. Previous studies showed that GH-releasing hormone
      (GHRH) stimulates galanin release from pituitary cells in vitro. In the present
      study we used human (h) GHRH transgenic mice to examine the effects of high
      circulating levels of GHRH on pituitary galanin gene expression in vivo.
      Moreover, the hGHRH transgenic mice develop pituitary tumors and, thus, may be
      used as a model of estrogen-independent pituitary adenoma formation. We examined
      male hGHRH transgenic mice and nontransgenic siblings at 2, 4, 6, 8, and 10
      months of age. Transgenic mice were identified using the polymerase chain
      reaction. Body weights and plasma mGH levels were higher in transgenic mice at
      all ages. Total protein contents in the anterior pituitary glands of transgenic
      mice were significantly greater at each age. Galanin peptide contents in the
      anterior pituitary gland of hGHRH mice were normalized for differences in total
      protein content and were significantly elevated at all ages examined. At 10
      months of age, anterior pituitary galanin peptide concentrations were increased 7
      fold. Hypothalamic concentrations of galanin peptide were also increased in hGHRH
      transgenic mice, but were not greater than those in nontransgenic siblings until
      4 months of age. In contrast, no significant differences in galanin peptide
      concentrations of the neurointermediate lobes were evident. Galanin mRNA
      concentrations in the anterior pituitary of 6-month-old transgenic mice were
      increased 4-fold. In conclusion, 1) galanin peptide concentrations in the
      anterior pituitary gland and hypothalamus are increased in hGHRH transgenic mice
      compared to those in nontransgenic siblings, whereas galanin peptide
      concentrations in the neurointermediate lobe are not different; 2) pituitary
      galanin mRNA concentrations are increased 4-fold in 6-month-old transgenic mice;
      and 3) the development of pituitary hyperplasia is correlated to the increase in
      galanin mRNA and peptide concentrations.

PMID- 7512493
TI  - Galanin in the bed nucleus of the stria terminalis and medial amygdala of the
      rat: lack of sexual dimorphism despite regulation of gene expression across
      puberty.
AB  - Neurons in the bed nucleus of the stria terminalis (BNST) and the medial amygdala
      (AMe) coexpress vasopressin and galanin (GAL) in the adult male rat. Here, we
      have asked whether GAL gene expression, like vasopressin gene expression in these
      same neurons, exhibits sexual dimorphism and whether GAL pathways in the BNST and
      AMe are activated with puberty in female rats as we have previously observed in
      male rats. In Exp 1, in situ hybridization histochemistry and quantitative
      autoradiography were used to compare GAL gene expression in the BNST and AMe of
      prepubertal (24-day-old) and adult (90-day-old) male and female rats. In the
      BNST, both the number of GAL mRNA-expressing neurons (F = 41.98; P < or = 0.0001;
      males, P < or = 0.007; females, P < or = 0.001) and the intensity of labeling (F
      = 40.35; P < or = 0.0001; males, P < or = 0.004; females, P < or = 0.002) were
      significantly increased in adult compared to prepubertal animals of both sexes.
      In the AMe of both males (P < or = 0.001) and females (P < or = 0.001), the
      intensity of labeling was significantly enhanced across puberty (F = 66.29; P <
      or = 0.0001); however, the number of GAL mRNA-expressing neurons in this region
      did not change. We found no evidence for sexual dimorphism of GAL gene expression
      in either brain region. In Exp 2, we replicated our observations of a lack of
      sexual dimorphism of GAL gene expression in the BNST of adult male and female
      rats. These findings are consistent with the hypothesis that GAL neurons in the
      BNST and AMe are steroid sensitive in both sexes. However, our failure to detect
      any differences in either the number of GAL mRNA-expressing neurons or the level
      of expression between male and female rats at either age indicates that these
      pathways do not exhibit sexual dimorphism.

PMID- 7512492
TI  - Activation-dependent regulation of galanin gene expression in gonadotropin
      releasing hormone neurons in the female rat.
AB  - In rats, galanin is colocalized in GnRH neurons, and galanin mRNA in GnRH neurons
      is increased coincidentally with the preovulatory gonadotropin surge. Whether the
      induction of galanin mRNA in GnRH neurons at proestrus reflects the action of sex
      steroids is unknown. We tested this hypothesis by challenging ovariectomized rats
      (n = 7) with estrogen and progesterone (E/P) to induce a LH surge and measuring
      galanin mRNA in GnRH neurons to determine whether there was an associated
      induction of galanin message in these cells. We used single and double label in
      situ hybridization and image analysis to compare among groups the levels of both
      galanin mRNA and GnRH mRNA in GnRH neurons. We found that steroid-primed animals
      showed an approximately 400% induction of galanin mRNA signal in GnRH neurons
      over that in vehicle-treated animals. Second, we hypothesized that steroid
      dependent events which induce the expression of galanin mRNA in GnRH neurons
      depend on transsynaptic input to GnRH neurons. We tested this hypothesis by
      examining the effect of a pharmacological blockade of the steroid-induced
      activation of GnRH neurons on levels of galanin mRNA in these cells. We killed
      groups of ovariectomized adult female rats at the peak of a E/P-primed LH surge
      (n = 7) and after steroid priming followed by blockade of the LH surge with
      either the general anesthetic pentobarbital (n = 7) or the specific alpha
      adrenergic receptor blocker phenoxybenzamine (n = 7). When we examined signal
      levels representing galanin mRNA content in GnRH neurons, we observed a 4-fold
      increase in signal for galanin mRNA in the GnRH neurons of steroid-primed (E/P
      surge) animals compared with that in oil-treated controls (P < 0.0004). This
      increase in galanin mRNA was prevented when the LH surge was blocked by treatment
      with either pentobarbital or phenoxybenzamine (P < 0.03 and P < 0.0001 vs. E/P
      surge controls, respectively). Cellular levels of GnRH mRNA were not different
      among control, E/P, and E/P plus pentobarbital groups (P > 0.2). These
      observations suggest that an increase in galanin mRNA levels in GnRH neurons is
      tightly coupled to the occurrence of a LH surge. By inference, induction of
      galanin mRNA in GnRH neurons reflects their activation, possibly via afferent
      neurons that transduce the steroid signal to GnRH neurons.

PMID- 7512495
TI  - Transforming growth factor-beta: a down-regulator of the parathyroid hormone
      related protein receptor in renal epithelial cells.
AB  - We have recently provided evidence for the ability of transforming growth factor
      beta 1 (TGF beta) to modulate PTH-related protein (PTHrP)-mediated responses in
      opossum kidney (OK) cells through reducing the number of PTHrP receptor-binding
      sites. In the present studies, we investigated the possible mechanisms by which
      TGF beta might regulate PTHrP receptor density in OK cells, an area that has
      remained largely unexplored. The steady state level of PTHrP receptor mRNA was
      time dependently reduced by TGF beta treatment, with the nadir (approximately 3
      fold decrease) between 6-10 h, preceding the maximal inhibition on PTHrP receptor
      binding at 18 h. We then assessed whether the 41% reduction in binding consequent
      to 18-h TGF beta exposure was reversible. PTHrP-binding activity recovered
      considerably after 24 h (23% decrease compared with controls) and almost
      completely by 48 h. However, the addition of monensin or cycloheximide, but not
      actinomycin (at a dose effective in preventing TGF beta action in this system)
      during the 24-h recovery period prevented restoration of PTHrP binding. Upon
      removal of TGF beta, the PTHrP receptor message showed a trend toward recovery in
      the ensuing 24 h. Therefore, TGF beta provides an example of heterologous
      desensitization of the PTHrP receptor in OK epithelial cells by decreasing the
      expression of the receptor message. The desensitization was reversible, and the
      first 24-h recovery phase was dependent on synthesis and processing of new
      receptor proteins.

PMID- 7512496
TI  - Coculture of primary rat hepatocytes and nonparenchymal cells permits expression
      of insulin-like growth factor binding protein-3 in vitro.
AB  - In biological fluids, the insulin-like growth factors (IGFs) are associated with
      binding proteins (IGFBPs), which modify IGF distribution and action. Circulating
      IGFs are bound predominantly to IGFBP-3, of apparent hepatic origin, but
      regulation of IGFBP-3 has been difficult to dissect because of the lack of
      systems suitable for examining hepatic production of IGFBP-3 in vitro. In the
      present studies, IGFBP-3 expression was identified primarily in hepatic
      nonparenchymal cells, particularly Kupffer and sinusoidal endothelial cells.
      Coculture with hepatocytes enhanced the stability of nonparenchymal cells to
      express IGFBP-3 in vitro. IGFBP-3 in conditioned medium had apparent mol wt of
      150-300 kilodaltons, suggesting formation of a ternary complex with IGFs and the
      acid-labile subunit. Expression and secretion of IGFBP-3 were hormonally
      responsive and strongly correlated (r = 0.79; P < 0.001), with 2- to 3-fold
      stimulation by added insulin or IGF-I (both P < 0.05), but not by added GH alone.
      Our findings suggest that GH may act indirectly to promote IGFBP-3 generation in
      vivo via increasing both the secretion of insulin and the hepatic production of
      IGF-I; in patients with diabetes mellitus, reduced circulating levels of IGFBP-3
      despite high levels of GH may result from both insulin deficiency and inadequate
      hepatic production of IGF-I. Coculture of hepatic nonparenchymal and parenchymal
      cells should be useful for further analysis of the mechanism of IGFBP-3
      regulation.

PMID- 7512497
TI  - Parallel regulation of parentally imprinted H19 and insulin-like growth factor-II
      genes in cultured human fetal adrenal cells.
AB  - Adjacent, parentally imprinted, insulin-like growth factor-II (IGF-II) and H19
      genes are highly expressed during embryogenesis and are important for fetal
      growth. Human fetal adrenals express abundantly both IGF-II and H19 genes. To
      clarify the significance and regulation of the H19 gene, we studied its
      expression in fetal adrenals. In situ hybridization experiments showed H19 RNA
      expression throughout the fetal adrenal cortex, with slightly higher expression
      in the outer definitive (adult) than in the inner fetal zone. In primary cultures
      of fetal adrenal cells, ACTH and other activators of the protein kinase-A signal
      transduction pathway increased both H19 and IGF-II RNA accumulation 1.7- to 10
      fold. Staurosporine, a protein kinase-C inhibitor, increased H19 and IGF-II RNA
      to the same extent as did ACTH. The protein kinase-C activator 12-O-tetradecanoyl
      phorbol-13-acetate and cytokines, tumor necrosis factor-alpha and interferon
      gamma, inhibited H19 and IGF-II RNA accumulation. Transforming growth factor-beta
      1 caused a decrease in levels of H19 and IGF-II RNA, whereas the IGFs caused a
      slight increase. Our data show parallel multifactorial regulation of H19 and IGF
      II RNAs in human fetal adrenal cells. This suggests common regulatory mechanisms
      for these adjacent genes.

PMID- 7512498
TI  - Effects of cytokines on insulin-like growth factor-binding protein secretion by
      muscle cells in vitro.
AB  - The insulin-like growth factors (IGF-I and IGF-II) stimulate muscle cell
      proliferation and/or differentiation (depending upon the culture conditions).
      They also increase IGF-binding protein (IGFBP) levels in muscle cell conditioned
      media and in some instances there is a direct correlation between the apparent
      rate of IGFBP secretion and muscle cell proliferation. We have investigated the
      effect of other cytokines on muscle cell IGFBP conditioned media levels using rat
      skeletal (L6), mouse myocytes (BC3H-I) and porcine vascular smooth (pVSM) muscle
      cells in vitro to determine if this relationship is maintained. IGFBP levels in
      conditioned media (CM) were measured by an [125I]IGF-I binding capacity assay and
      by western blot analysis. Immunoblots indicated that BC3H-1 and L6 cells secrete
      IGFBP-5 (31-32,000 M(r)), L6 cells secrete IGFBP-4, and pVSM cells secrete IGFBP
      2 (34,000 M(r)). Both L6 and BC3H-1 cells responded to transforming growth factor
      beta 1 (TGF-beta 1), in a dose-dependent manner, with suppressed conditioned
      media levels of IGFBP-4 and IGFBP-5 but TGF-beta 1 did not affect IGFBP-2 levels
      in pVSM cell media. TGF-beta 1 (5 ng/ml) suppressed IGFBP levels (CM [125I]IGF-I
      binding capacity) in L6 and BC3H-1 cell media by 48% and 61%, respectively. IGFBP
      5 levels, in BC3H-1 cell media, were decreased by treatment with either basic
      fibroblast growth factor (bFGF) or epidermal growth factor (EGF). Neither
      treatment affected IGFBP-2 levels. In contrast in L6 myoblasts, bFGF increased
      media levels of IGFBP-4 and IGFBP-5; L6 cells were not responsive to EGF. Insulin
      increased IGFBP-4 and IGFBP-5 levels in L6 and BC3H-1 cell media. This
      stimulatory effect was markedly suppressed by either TGF-beta 1 (L6 and BC3H-1
      cells) or bFGF (BC3H-1 cells). L6 and BC3H-1 cell CM IGFBP levels were also
      suppressed 34% and 84% by 5 U/ml thrombin, respectively. The inhibitory activity
      of thrombin was specific, i.e. reversible by hirudin and was not due to direct
      IGFBP proteolysis. Since suramin and staurosporine increased media levels of the
      IGFBP, this suggests that constitutive secretion of TGF-beta 1, bFGF, or EGF
      might provide a tonic suppressive mechanism for controlling IGFBP secretion.
      Thus, our results support the conclusion that the secretion of IGFBP-4 and IGFBP
      5, but not IGFBP-2, by muscle cells was suppressed by several cytokines.
      Depressed IGFBP secretion may play a key role in determining muscle cell
      responsiveness to either the mitogenic or differentiation stimulating activity of
      the IGFs.

PMID- 7512499
TI  - Administration of growth hormone (GH), but not insulin-like growth factor-I (IGF
      I), by continuous infusion can induce the formation of the 150-kilodalton IGF
      binding protein-3 complex in GH-deficient rats.
AB  - In the adult circulation, 70-90% of the serum insulin-like growth factors (IGFs)
      are carried by IGF-binding protein-3 (IGFBP-3), which exists as part of a 150
      kilodalton (kDa) ternary complex including IGF and an acid-labile subunit (ALS).
      We have examined the hormonal regulation and molecular distribution of IGFBP-3 in
      the circulation of a uniquely GH-deficient (GHD) rat model. For 7 days, GHD rats
      were given GH by either twice daily injections (1 mg/kg) or continuous infusion
      (2.4 mg/kg.day) or IGF-I by continuous infusion (1.4 mg/kg.day). Each day, weight
      and feed and water intake were monitored, and on day 7, liver, kidney, spleen,
      heart, and lung were weighted, and sera were collected. Serum IGF-I was analyzed
      by immunoassay, and the molecular distribution of the IGFBPs was determined by
      neutral size-exclusion chromatography combined with Western ligand blot and
      Western immunoblot. The GHD rats were 40-60% lighter than their normal
      littermates, and all organs examined were proportionately smaller. Serum IGF-I
      and IGFBP-3 levels were less than 10% of those in normal rats. Incubation of
      serum from GHD rats with [125I]IGF-II showed that radiolabel was incorporated
      only into a 44-kDa IGFBP region that contained the smaller IGFBPs. IGFBP-3 eluted
      around 60 kDa. No 150-kDa IGFBP region was detected. The administration of GH or
      IGF-I to GHD rats resulted in significant increases in weight gained, although
      food and water intake remained unaltered. Weight gain was observed in all three
      treatments groups. Both GH treatment regimens significantly increased liver,
      spleen, and lung weight, whereas IGF-I therapy increased spleen, kidney, and
      heart. Administration of GH twice daily did not increase serum IGF-I or IGFBP-3
      concentrations, and the molecular distribution of IGFBP-3 remained unchanged. In
      contrast, continuous infusion of GH resulted in 5-fold increases in serum IGF-I
      and increases in IGFBP-3 levels. Size-exclusion chromatography combined with
      Western ligand blot analysis revealed that radioligand was incorporated into 150-
      and 60-kDa regions, and that IGFBP-3 was detectable in both regions. Thus, GH
      infusion was able to induce formation of the 150-kDa ternary complex by
      increasing circulating levels of IGF-I, IGFBP-3, and presumably ALS.
      Administration of IGF-I also increased serum IGF-I and IGFBP-3 levels, although
      the increase in IGFBP-3 was only in the 60-kDa region of the chromatograph,
      suggesting that IGF-I can induce neither ALS nor formation of the 150-kDa
      complex.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7512500
TI  - Characterization of two classes of ribonucleoprotein complexes possibly involved
      in RNA editing from Leishmania tarentolae mitochondria.
AB  - The molecular mechanism of RNA editing in trypanosomatid mitochondria is an
      unsolved problem. We show that two classes of ribonucleoprotein complexes exist
      in a mitochondrial extract from Leishmania tarentolae and appear to be involved
      in RNA editing. The 'G' class of RNP complexes consists of 170-300 A particles
      which contain guide RNAs and proteins, show little terminal uridylyl transferase
      (TUTase) activity and exhibit an in vitro RNA editing-like activity. The 'T'
      class consists of approximately six RNP complexes, the endogenous RNA of which
      can be self-labeled with [alpha-32P]UTP. The most abundant T complex, T-IV, is
      visualized by electron microscopy as 80-140 A particles. This complex exhibits
      TUTase activity in the native gel and contains guide RNAs. Both G and T complexes
      are possibly involved with RNA editing in vivo. These results are a starting
      point for the analysis of the biochemistry of RNA editing.

PMID- 7512501
TI  - Release of GPI-anchored membrane proteins by a cell-associated GPI-specific
      phospholipase D.
AB  - Although many glycosylphosphatidylinositol (GPI)-anchored proteins have been
      observed as soluble forms, the mechanisms by which they are released from the
      cell surface have not been demonstrated. We show here that a cell-associated GPI
      specific phospholipase D (GPI-PLD) releases the GPI-anchored, complement
      regulatory protein decay-accelerating factor (DAF) from HeLa cells, as well as
      the basic fibroblast growth factor-binding heparan sulfate proteoglycan from bone
      marrow stromal cells. DAF found in the HeLa cell culture supernatants contained
      both [3H]ethanolamine and [3H]inositol, but not [3H]palmitic acid, whereas the
      soluble heparan sulfate proteoglycan present in bone marrow stromal cell culture
      supernatants contained [3H]ethanolamine. 125I-labeled GPI-DAF incorporated into
      the plasma membranes of these two cell types was released in a soluble form
      lacking the fatty acid GPI-anchor component. GPI-PLD activity was detected in
      lysates of both HeLa and bone marrow stromal cells. Treatment of HeLa cells with
      1,10-phenanthroline, an inhibitor of GPI-PLD, reduced the release of
      [3H]ethanolamine-DAF by 70%. The hydrolysis of these GPI-anchored molecules is
      likely to be mediated by an endogenous GPI-PLD because [3H]ethanolamine DAF is
      constitutively released from HeLa cells maintained in serum-free medium.
      Furthermore, using PCR, a GPI-PLD mRNA has been identified in cDNA libraries
      prepared from both cell types. These studies are the first demonstration of the
      physiologically relevant release of GPI-anchored proteins from cells by a GPI
      PLD.

PMID- 7512502
TI  - The endothelin ETA receptor antagonist, BQ-123, normalizes the response of SHR
      aorta to Ca2+ channel activator.
AB  - Hypertension is associated with a hypersensitive response to the Ca2+ channel
      activator, Bay K 8644. We investigated the effect of the endothelin ETA receptor
      antagonist, BQ-123, on the contractions induced by Bay K 8644 in aorta from
      spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. BQ-123
      (1 microM) decreased the sensitivity to Bay K 8644 of aorta of SHR down to that
      of WKY. This observation is consistent with a role for endothelin in
      hypertension.

PMID- 7512504
TI  - Effects of K+ channel openers on the vascular actions of human gamma globulin.
AB  - The aim of this study was to determine if the stimulatory action of human gamma
      globulin on the spontaneous activity of the rat mesenteric portal vein is due to
      decreased K+ conductance. Glibenclamide potentiated the action of human gamma
      globulin on the portal vein by 45% and on its own had a concentration- and time
      dependent biphasic (increase followed by a decrease) effect on the spontaneous
      activity of the portal vein. Diazoxide and pinacidil both inhibited the action of
      human gamma-globulin on the rat mesenteric portal vein. Levcromakalim (BRL 38227)
      potentiated the stimulatory action of human gamma-globulin on the integrated
      force of the spontaneous contractions of the rat mesenteric portal vein by 40%
      and 49% at concentrations of 0.5 and 5 microM, respectively. These studies
      suggest that human gamma-globulin can act by directly modulating a K+ channel.

PMID- 7512503
TI  - Characterization of the muscarine receptor subtype on sympathetic nerve endings
      in the rat caudal artery.
AB  - The prejunctional muscarine receptor on sympathetic nerves in the rat caudal
      artery was characterized using several selective antagonists. The inhibitory
      response of carbachol on vasoconstriction elicited by sympathetic nerve
      stimulation was antagonized by benzhexol (trihexyphenidyl; pKB 7.1), heptane-1,7
      bis(dimethyl-3'-phthalimidopropyl ammonium bromide) (C7/3-phth; pKB 6.5) and
      hexahydrosiladifenidol (HHSiD; apparent pKB 6.0). These pKB values suggest that
      the receptor most closely resembles the muscarine M2 receptor subtype rather than
      the muscarine M1, M3 or M4 receptor subtypes.

PMID- 7512505
TI  - Dual effects of nicardipine: evidence from intracellular Ca2+ transients and
      twitch contractions observed in single myocytes obtained from rat heart.
AB  - Mechanisms responsible for dual actions of nicardipine were examined using
      myocytes isolated from ventricular muscle of rat heart. About 60% of isolated rat
      myocytes showed positive force-frequency relationships. These cells had lower
      intracellular Ca2+ concentrations at rest. In the remaining cells that had higher
      resting Ca(2+)-concentrations, an increase in frequency of stimulation from 1 Hz
      to 2 Hz produced either no change or reduction in the amplitude of Ca2+
      transients and twitch contractions. In 13 of 34 myocytes that showed positive
      force-frequency relationships, nicardipine enhanced the Ca2+ transient and
      produced sustained positive inotropic effects. In 11 of 20 cells that showed
      negative force-frequency relationships, nicardipine produced negative inotropic
      effects. Inhibition was partly reversed by an increase in extracellular CaCl2
      concentration from 1.2 to 3.6 mM. In the remaining cells, nicardipine failed to
      either increase or decrease the amplitude of Ca2+ transient or twitch
      contraction. Bay K-8644 produced positive inotropic effects in most cells. These
      results indicate that nicardipine either enhances or inhibits Ca2+ transients and
      twitch contractions depending on the Ca2+ loading state of myocytes. The present
      results are consistent with the hypothesis that nicardipine stabilizes the state
      of Ca2+ channels, either in the inactivated state in cells that are well loaded
      with Ca2+, or in the activated state when the degree of Ca2+ loading is
      relatively low.

PMID- 7512508
TI  - E-selectin in the pathogenesis of experimental myocardial ischemia-reperfusion
      injury.
AB  - The role of E-selectin in the pathogenesis of an experimental model of myocardial
      ischemia-reperfusion injury was investigated. Pentobarbital anesthetized rats
      underwent left main coronary artery ligation (1 h) followed by reperfusion (1 h;
      MI/R). Sham operated rats were used as controls (sham MI/R). Myocardial ischemia
      reperfusion injury reduced survival rate (50%), caused severe myocardial damage
      (necrotic area/area-at-risk 69.8 +/- 5%; necrotic area/total area = 56 +/- 7.6%),
      increased serum creatine phosphokinase activity (sham MI/R = 33 +/- 3 U/ml; MI/R
      = 215 +/- 13 U/ml), and elevated myeloperoxidase activity (investigated as an
      index of leukocyte adhesion and accumulation; sham MI/R = 0.11 +/- 0.02 U x 10(
      3)/g tissue) in the area-at-risk (7.5 +/- 1.7 U x 10(-3)/g tissue) and in the
      necrotic area (7.8 +/- 2.2 U x 10(-3)/g tissue). Furthermore, MI/R rats had an
      increased pressure rate index, studied as a quantitative means for assessing
      myocardial oxygen demand. Administration of a hyperimmune serum containing
      antibodies against E-selectin significantly improved survival rate (80%), reduced
      myocardial injury (necrotic area/area-at-risk = 26.4 +/- 7%, P < 0.005; necrotic
      area/total area 19.1 +/- 2.8%, P < 0.005), lowered serum creatine phospokinase
      activity (85 +/- 5 U/ml, P < 0.001) and decreased myeloperoxidase activity in the
      area at risk (3.7 +/- 1.3 U x 10(-3)/g tissue, P < 0.001) and in the necrotic
      area (3.0 +/- 0.7 U x 10(-3)/g tissue). Finally, the administration of anti E
      selectin antibodies improved the PRI in MI/R rats. The present data suggest that
      E-selectin in vivo plays a key role in the pathogenesis of myocardial
      ischemia/reperfusion injury.

PMID- 7512507
TI  - Ethanol inhibition of L-type Ca2+ channels in PC12 cells: role of permeant ions.
AB  - The effects of acute ethanol exposure on voltage-activated Ca2+ channels in
      undifferentiated pheochromocytoma (PC12) cells were investigated using whole-cell
      patch clamp techniques. Concentrations of ethanol (5, 25 and 50 mM), at or below
      blood alcohol levels which constitute legal intoxication significantly reduced
      Ca2+ currents evoked from a holding potential of -30 mV. Ethanol-induced
      inhibition of current was voltage-dependent in some cases, but this was not
      consistently observed. Inhibition of currents was reversible and was not due to
      an osmotic effect. The non-inactivating nature of the current, the inhibition of
      the current by nifedipine, and the lack of inhibition by omega-conotoxin,
      indicated that the current was carried through high-voltage activated, L-type
      Ca2+ channels. Since intracellular Ca2+ levels were highly buffered by exchanged
      with the contents of the patch pipet, ethanol-induced inhibition of currents in
      PC12 cells is not likely to involve either a change in driving force due to a
      change in intracellular Ca2+ levels or potentiation of Ca(2+)-dependent Ca2+
      channel inactivation by the influx of Ca2+. The degree of inhibition by 25 mM
      ethanol was the same when either Ca2+, Ba2+ or Na+ was used as the current
      carrying ion. This equivalency suggest that the channel's ion selectivity filter
      is not a site of action for ethanol.

PMID- 7512506
TI  - Dexamethasone potentiates NMDA receptor-mediated neuronal injury in the postnatal
      rat.
AB  - The present study investigated the effect of a synthetic glucocorticoid,
      dexamethasone, on excitatory amino acid receptor-mediated neurotoxicity in the 7
      day-old rat. Pretreatment with dexamethasone (0.7 mg/kg i.p.) 1 h prior to
      unilateral intrastriatal injection of excitotoxin enhanced damage resulting from
      N-methyl-D-aspartate (NMDA), but not alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA), or kainate receptor activation. The glucocorticoid
      induced enhancement of NMDA toxicity was dose dependent. The time of
      dexamethasone administration appeared critical since only treatment 1 h prior to,
      but not 24 h prior to, simultaneously with, or 1 h after NMDA injection, affected
      toxicity. The administration of the adrenal mineralocorticoid aldosterone, or the
      phospholipase A2 inhibitor mepacrine, did not affect excitotoxicity. Quantitative
      receptor autoradiography was performed to assess the effect of dexamethasone on
      NMDA-sensitive [3H]glutamate receptor binding. Neither pretreatment in vivo nor
      the addition of dexamethasone in vitro affected NMDA-sensitive binding in the
      striatum. Possible explanations for these observations are discussed.

PMID- 7512509
TI  - Decreased opsin mRNA and immunoreactivity in progressive rod-cone degeneration
      (prcd): cytochemical studies of early disease and degeneration.
AB  - Opsin mRNA level and immunoreactivity were examined by in situ hybridization and
      immunocytochemistry in normal and progressive rod cone degeneration (prcd)
      affected dogs. In situ hybridization used 35S- and/or 3H-labeled bovine opsin
      cRNA probes; immunocytochemistry used six monoclonal mouse anti-bovine opsin
      antibodies (MAb1) that are specific to different regions of the N-terminal, loop
      v-vi and the C-terminal domains. Optimal labeling and histological resolution at
      the single cell level were achieved with semi-thin sections of DGD wax-embedded
      tissues; it was possible to correlate the cytochemical observations with the
      disease staging in topographically defined regions that exhibited different
      disease severity. In early disease (stages 0-1), opsin mRNA levels and
      immunoreactivity were normal. During the transition from disease to degeneration
      (stage 2), however, opsin mRNA was reduced sharply; it then rapidly became
      undetectable in late stages of degeneration (stages 3, 4). Reduction of
      immunoreactivity was seen with all the MAbs in stages 2 and 3, but the degree of
      reduction varied remarkably in different regions of the protein molecule;
      immunoreactivity was reduced more in the cytoplasmic regions, particularly in the
      phosphorylation sites and the far end of the C-terminal domain. In contrast, the
      epitopes of the N-terminal domain that are located in the intradiscal compartment
      were better preserved. It is noteworthy that, in stages 2 and 3, many rod cells
      still survived despite the decrease in the mRNA level and immunoreactivity. The
      results indicate that early disease in prcd-affected rods is not initiated by a
      reduction of opsin mRNA or the protein quantity. However, opsin expression
      disappears in early degeneration and before cell death. The differences in
      immunoreactivity with disease may result either from alterations in the protein
      structure or configuration, or from selective loss of epitopes located in the
      cytoplasmic domains of the molecule.

PMID- 7512512
TI  - Axonal transport of proteoglycans in regenerating goldfish optic nerve.
AB  - Labeling of goldfish optic nerve and tectum proteoglycans (PGs) was quantified
      following intraocular injection of 35SO4 and [3H]proline or [3H]glucosamine. Both
      intact animals and animals which had survived for periods of 10 to 119 days after
      an optic nerve crush lesion were examined. Regenerating retinal ganglion cell
      (RGC) axons reached the rostral pole of the tectum by 10 days postcrush and by 21
      days had densely innervated the optic synaptic laminae. If the contralateral
      tectum had been removed, the regenerating RGC axons innervated the remaining
      ipsilateral tectum with a delay of approximately 14 days. There was a biphasic
      increase in the synthesis and transport of PGs during optic fiber regeneration
      which was not affected by the removal of the tectum. More highly sulfated PGs
      were preferentially off-loaded from the orthograde transport pool proximally in
      the optic nerve, both in the unoperated animals and during regeneration. These
      PGs also had longer and/or more glycosaminoglycan (GAG) chains than those off
      loaded distally, in the tectum. During early regeneration, the synthesis and
      transport of chondroitin sulfate PGs (CSPGs) increased more than those of heparan
      sulfate PGs, and during the period of optic fiber invasion of the synaptic
      laminae, the PGs retained in the nerve had a higher content of CSPGs than those
      transported into the tectum. Removal of the contralateral tectum at the time of
      nerve crush resulted in a decrease in the size and/or numbers of GAGs and overall
      sulfation of PGs in the nerve by 21 days postoperatively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7512511
TI  - M2-type muscarinic receptors mediate prejunctional inhibition of norepinephrine
      release in the human iris-ciliary body.
AB  - Human muscarinic receptors comprise a family of five separate gene products,
      three of which (designated as M1, M2 and M3 subtypes) can be distinguished
      pharmacologically. Previous work indicates that sympathetic nerve terminals in
      the anterior uvea contain prejunctional muscarinic receptors that, upon
      activation by agonists, inhibit the neural release of norepinephrine. The aim of
      this study was to characterize the prejunctional effects of muscarinic agents on
      the electrically-evoked secretion of 3H-norepinephrine in isolated, superfused
      human iris-ciliary body tissue segments. Stimulation-evoked 3H-norepinephrine
      release was inhibited > 80% by carbachol and muscarine, but was unaffected by the
      M1-selective agonist McN A-343. Pilocarpine behaved as a partial agonist in this
      system, producing less than 40% of the maximum inhibition. The rank order of
      potency of selective antagonists at prejunctional muscarinic receptors was
      methoctramine (M2) > AF-DX 116 (M2) > pirenzepine (M1) > or = para-fluoro
      hexahydro-sila-definidol (M3). These data suggest that prejunctional muscarinic
      receptors in the human iris-ciliary body correspond to the M2 subtype. No
      evidence for age-related differences in prejunctional muscarinic receptor
      activity was seen in tissues obtained from 13 human donors, aged 10-83 years.
      Prejunctional muscarinic receptors may play a role in mediating the inhibitory
      effects of parasympathetic nerve stimulation or cholinomimetic drugs on ocular
      sympathetic neurotransmission in vivo.

PMID- 7512510
TI  - Subretinal neovascularization in the rat induced by IRBP synthetic peptides.
AB  - The present study was undertaken to develop a new animal model of subretinal
      neovascularization that does not involve traumatic manipulation of the eye. Using
      this model, the mechanism of subretinal neovascularization and its penetration
      through Bruch's membrane, and the various factors that contribute to this process
      were then examined. Male Lewis rats were immunized with interphotoreceptor
      retinoid binding protein (IRBP) peptide R-4, and the eyes histologically examined
      at various times up to 45 days after immunization. On day 12 after immunization,
      inflammatory cells were identified primarily in the anterior segment of the eye,
      with scattered cells in the retina and choroid. The inflammation was most
      prominent on day 14, by which time many eyes showed serous retinal detachment. By
      day 18 the inflammation had declined in intensity, but branches of the retinal
      vessels were seen extending into the choroid. Examination on day 30 revealed even
      fewer inflammatory cells but an accumulation of retinal pigment epithelial cells
      and mononuclear cells was present in the subretinal space. Examination on day 45
      revealed no appreciable inflammation, but typical new vessels were found in the
      eyes from five of the 13 rats (38%) examined at that point. Mild inflammation of
      the retinochoroidal tissue can induce subretinal new vessels in rats, and this
      model will be useful for further study of subretinal new vessel formation.

PMID- 7512513
TI  - Unilateral destruction of dopamine pathways increases ipsilateral striatal
      serotonin turnover in rats.
AB  - In order to evaluate the influence of dopaminergic transmission on regional brain
      utilization of serotonin (5HT), the effects of the destruction of the ascending
      dopamine (DA) pathways on regional brain 5HT metabolism in the rat were examined.
      Complete unilateral lesions of the nigrostriatal DA pathways (> 90% DA loss) were
      made by infusing the neurotoxin 6-hydroxy-dopamine into either the left medial
      forebrain bundle (MFB) or the left substantia nigra (SN). At 6 weeks after the
      lesions, levels of 5HT and its major metabolite, 5-hydroxyindoleacetic acid
      (5HIAA), were determined bilaterally in the striatum, frontal cortex, and
      hypothalamus. In the striatum of the lesioned hemisphere, the 5HT level decreased
      by more than 50%, while the ratio of 5HIAA:5HT (an index of 5HT turnover)
      increased by more than 90%. In the same rats, cortical and hypothalamic 5HT,
      5HIAA, and 5HT turnover were not changed as a result of the MFB or SN lesions.
      These results suggest that the loss of DA innervation in the striatum triggers an
      increase in 5HT turnover and a net depletion of 5HT in the striatum. To verify
      that the loss of DA was responsible for the observed striatal 5HT changes, we
      examined the effect of intracerebral implantation of DA-containing pellets into
      one group of MFB-lesioned rats. The lesioned rats with placebo pellets did not
      differ from lesioned rats without pellets, whereas the implantation of DA pellets
      reversed the lesion-induced changes in the 5HT levels and 5HIAA:5HT
      ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512514
TI  - The use of intravenous gammaglobulin, heparin and aspirin in the maintenance of
      pregnancy of freeze thawed embryo in a patient with lupus-type anticoagulant.
AB  - A case of lupus anticoagulant and repeated fetal loss with a successful delivery
      of a healthy baby after transfer of thawed frozen embryos and intravenous
      immunoglobulin administration is described. The repeated fetal loss was due to
      vascular disturbances caused by lupus anticoagulants. Early implantation was not
      affected. Anticoagulants and/or steroids did not help in further establishing
      pregnancy. Intravenous immunoglobulin combined with heparin and aspirin led to
      term pregnancy and the birth of a healthy child.

PMID- 7512515
TI  - Children who develop epilepsy in the first year of life: a prospective study.
AB  - A long-term prospective study was carried out of 133 children diagnosed as having
      epilepsy in the first year of life, of whom two-thirds had West syndrome and one
      third had other forms of epilepsy. They were followed for a minimum of three
      years (half for over seven years), during which time 15 children died. Of the 118
      surviving, 54 had an IQ of > 70, but 53 were severely mentally impaired, of whom
      two-thirds had West syndrome. Only 56 per cent currently have no seizures, and no
      significant differences were found in this respect between children with West
      syndrome and those with other forms of epilepsy. Regression in mental development
      occurred significantly more frequently among children with active epilepsy. These
      results lead to the conclusion that the degree and type of central nervous system
      damage existing at the onset of epilepsy is decisive for the outcome of the
      child, but the cessation of epileptic seizures also improves the child's
      developmental possibilities.

PMID- 7512516
TI  - Fetal valproate syndrome: clinical and neuro-developmental features in two
      sibling pairs.
AB  - The clinical and neurodevelopmental features are presented of four children--two
      sibling pairs--who were exposed in utero to valproic acid. One of each pair of
      children presented for diagnosis and assessment of developmental delay; the other
      sibling was examined at a later date. Three of the children were globally
      developmentally delayed with marked speech disability, and had dysmorphic
      features consistent with fetal valproate syndrome. One also had features of
      infantile autism. The fourth child had some of the dysmorphic features connected
      with fetal valproate syndrome, but had normal intellect, with his verbal ability
      being significantly below his non-verbal ability. He currently attends a school
      for learning-disabled children.

PMID- 7512517
TI  - Regulation of IgE synthesis.
AB  - The role of IgE in allergic disease is by now well recognized. The study of the
      cellular basis of IgE regulation has been actively pursued to gain insights into
      the pathogenesis of a disease that affects a considerable proportion of the
      population. More recently, the molecular events underlying IgE synthesis have
      become the focus of intense interest, in an attempt to characterize the signals
      involved in isotype-specific regulation of immunoglobulin synthesis. Recent
      evidence from different laboratories indicates that induction of IgE synthesis
      requires two signals: one is IgE isotype-specific, and is delivered by IL-4, the
      other is a B cell activating signal that can be delivered through a variety of
      pathways. We will herein review what is currently known about the mechanisms
      underlying the synthesis of IgE in humans, as they are revealed through cellular
      and molecular biology studies.

PMID- 7512518
TI  - Leukocyte adhesion molecules in rejected corneal allografts.
AB  - Leukocyte adhesion molecules are believed to play a key role in the selective
      recruitment of different leukocyte populations to inflammatory sites. In this
      study, we investigated the presence and distribution of intercellular adhesion
      molecule-1 (ICAM-1), E-selectin (endothelial leukocyte adhesion molecule-1) and
      vascular cell adhesion molecule-1 (VCAM-1) in 12 rejected corneal allografts and
      compared the presence of these adhesion molecules with the composition of the
      associated inflammatory infiltrates. ICAM-1 was focally expressed on corneal
      epithelial cells and its expression was increased on keratocytes, corneal and
      vascular endothelial cells particularly at the site of dense infiltration with
      mononuclear leukocytes. E-selectin was present on endothelial cells of vessels in
      the stroma of rejected corneal allografts which were characterized by dense
      infiltration with T cells and macrophages. VCAM-1 was predominantly expressed on
      inflammatory cells of the macrophage/monocyte lineage, but only sporadically on
      vascular endothelial cells in the stroma of vascularized rejected corneal
      allografts. Our results suggest that ICAM-1, E-selectin and VCAM-1 may all be
      involved in the pathogenesis of corneal allograft rejection, particularly in the
      generation of the inflammatory infiltrates.

PMID- 7512519
TI  - Dissociation in serum CA125 concentrations measured by different monoclonal
      antibodies.
AB  - The new immunoradiometric assay for CA125 (CA125II assay) uses the monoclonal
      antibody M11 as an immunoadsorbent. The epitope recognized by M11 is different
      from the OC125 epitope. Monoclonal antibodies 130-22 and 145-9 recognize an
      epitope designated as CA130 on the molecule expressing the OC125 epitope.
      Similarity of M11 epitope to the epitope of anti-CA130 antibodies and
      dissociation of antigen levels measured by the original CA125 assay and new
      CA125II assay were examined. Anti-CA130 antibodies partially competed with M11
      for the M11 epitope. Among more than 20,000 serum samples we found 12 patients in
      whom the serum CA125 concentration measured by the CA125II assay was different
      from that measured by the original assay. In 11 out of 12 patients the CA125
      concentration was moderately or extremely high by the original assay but very low
      by the CA125II assay. Eight of the 11 patients had benign disease, one had no
      apparent disease and two had cancer. The antigen level determined by CA130 assay
      was very low in all the 11 patients. In one patient the CA125II assay showed a
      higher antigen level than the original assay or CA130 assay. The heterogeneity of
      the epitope expression could cause the dissociation of CA125 levels measured by
      the different monoclonal antibodies.

PMID- 7512520
TI  - Plasmin modulators, aprotinin and anti-catalytic plasmin antibody, efficiently
      inhibit destruction of bovine vascular endothelial cells by choriocarcinoma
      cells.
AB  - The interaction of human gestational choriocarcinoma cell line, SMT-cc1, with
      bovine vascular endothelial cells, CPAE, was examined in an in vitro coculture
      model. SMT-cc1 cells have urokinase-type plasminogen activator (uPA) on their
      cell surface, and more than half of the cell-associated uPA is enzymatically
      inactive single-chain uPA (pro-uPA). uPA is bound to a specific surface receptor
      that is not completely saturated. Also, the plasmin activity is detected on their
      cell surface. We measured the ability of added SMT-cc1 cells to cause
      morphological changes in CPAE cells, leading to destruction of CPAE cells. SMT
      cc1 cells that adhered to CPAE cell monolayers were capable of causing CPAE cell
      destruction, followed by detachment, within 6 hr after coculture. Nonspecific
      serine proteinase inhibitor, aprotinin, and anti-catalytic antibody against
      plasmin(ogen) effectively inhibited the destruction/detachment in a dose
      dependent manner. SMT-cc1 cell-mediated CPAE cell destruction was suppressed for
      6 hr in the presence of aprotinin, at a concentration of 20 micrograms/ml, or
      anti-plasmin antibody, at a concentration of > or = 10 micrograms/ml, suggesting
      that the destruction is closely related to the proteolytic enzyme, plasmin. We
      suggest that the destruction of endothelial cells by some tumor cells is
      associated with tumor cell-associated proteolytic activity, and the uPA-plasmin
      cascade plays an important role as a critical step during blood-borne metastasis.

PMID- 7512523
TI  - Primary malignant lymphoma of the uterine cervix shows favorable response to
      neoadjuvant chemotherapy.
AB  - Primary malignant lymphoma localized in the uterine cervix is a rare condition
      for which radiation therapy, surgery, or chemotherapy either alone or in
      combination have been the mainstay of treatment. The effectiveness of neoadjuvant
      chemotherapy for this condition, however, has not been evaluated. We experienced
      one case of primary malignant lymphoma of the uterine cervix, stage IIa according
      to FIGO, and IEA according to the Ann Arbor staging system for extranodal
      lymphomas, which was treated with neoadjuvant chemotherapy and surgery. The
      patient first underwent neoadjuvant chemotherapy consisting of cyclophosphamide,
      vinblastine, epirubicin, bleomycin, procarbazin, and oncovin (COP-BLAM) to reduce
      the size of the tumor. This was followed by an extended total hysterectomy, left
      salpingo-oophorectomy, and bilateral pelvic lymph node dissection. Neoadjuvant
      chemotherapy given before surgery resulted in a remarkable reduction in the tumor
      size which made the subsequent surgery technically easy. In addition, it is
      possible that intraoperative micrometastasis of the tumor cells could be better
      prevented. The patient received additional chemotherapy with COP-BLAM schedules
      postoperatively. No evidence of recurrent lymphoma has been observed in 2 years
      after the treatment. Neoadjuvant chemotherapy may be an effective treatment
      modality for primary malignant lymphoma of the uterine cervix.

PMID- 7512522
TI  - Oncolytic activity of NK cells against SW-756 squamous cervical carcinoma cell
      line: role of interferons alpha and gamma and CD54 adhesion molecule in
      oncolysis.
AB  - We investigated the sensitivity of a cervical tumor cell line SW-756 to lysis by
      peripheral blood mononuclear cells (MNC), natural killer (NK) cells, and major
      histocompatibility complex (MHC)-nonrestricted (MHC-NR) T cells from cervical
      cancer patients and normal donors. We found that SW-756 was resistant to lysis
      mediated by naive (unstimulated) MNC and MHC-NR T cells, but sensitive to lysis
      by naive NK cells. However, the cytotoxic function of MNC could be activated with
      interleukin-2 (IL-2) and interferon (IFN) alpha or gamma. Although IFNs were
      effective in enhancement of effector cell cytotoxicity and inhibited
      proliferation of cervical tumor cells, they also exerted an adverse effect on
      cytotoxicity; specifically, pretreatment of SW-756 cells with IFNs significantly
      decreased their susceptibility to lysis by effector cells. Analysis of surface
      phenotype of SW-756 cells after treatment with IFNs showed up-regulation of
      expression of HLA class I determinants, the phenomenon that may be responsible
      for decreased sensitivity of this tumor to MHC-NR NK cells. The studies on the
      involvement of CD54 adhesion molecule in cytotoxic functions indicated that
      expression of this molecule on effector cells (but not on target cells) was
      important for cytotoxicity against SW-756 tumor cells. The therapeutic
      implication of these studies for patients with cervical cancer is discussed.

PMID- 7512521
TI  - In vitro growth effects of colony-stimulating factors in ovarian cancer.
AB  - Human recombinant colony-stimulating factors may be used to treat or prevent
      neutropenia caused by marrow toxic chemotherapeutic agents administered to
      patients with cancer. Despite their common clinical use, little is known about
      the potential adverse effects that these cytokines may have on the growth of
      malignant cells. Indeed, several in vitro reports have indicated that colony
      stimulating factors may act as stimulating growth factors in some human
      malignancies. To evaluate these effects in ovarian cancer, we investigated the
      possible growth effects of granulocyte colony-stimulating factor (G
      CSF/Filgrastim) and granulocyte-macrophage colony-stimulating factors (GM
      CSF/Sargramostim) on four established ovarian cancer cell lines, as well as five
      primary ovarian cancer cultures over a wide range of pharmacologic doses. Cell
      viability was measured by an ATP bioluminescence assay and expressed as a
      percentage of untreated control cultures. G-CSF showed no growth-stimulating
      effects in any of the four established cell lines tested. In the OVCAR-3 cell
      line, a decrease in growth (> 10%) was seen at 10, 100, and 1000 ng/ml after 5
      days of continuous treatment. In the same cell line, GM-CSF caused an increase (>
      10%) in growth at the same doses. However, these changes did not demonstrate
      statistical significance in a dose-dependent fashion. In the five primary
      cultures treated with G-CSF, only one demonstrated statistically significant
      increases in growth in a dose-dependent manner. GM-CSF treatment had no
      significant growth alterations in these same five primary cultures. These results
      would suggest that colony-stimulating factors may act as growth factors in some
      but not all ovarian cancer cells. Further investigations into the receptor status
      of ovarian cancer cells for these cytokines are underway to clarify this issue.

PMID- 7512524
TI  - Induction of Lyt-2+ cytotoxic T lymphocytes following primary and secondary
      Salmonella infection.
AB  - Investigations of the cytotoxic activity of T cells induced following one or two
      intraperitoneal doses of live Salmonella revealed that cytotoxicity was
      restricted to the Lyt-2+ T-cell subset and was enhanced following secondary
      infection with Salmonella. Initial studies using the lectin-dependent cellular
      cytotoxicity (LDCC) assay detected Lyt-2+ cytotoxic T cells in peritoneal cell
      suspensions of S. enteritidis 11RX (11RX)-infected mice, with the peak of
      activity occurring 5 days after infection. This did not correlate with the
      proliferative activity of these cells, which peaked 10-12 days after infection.
      Secondary challenge with 11RX or S. typhimurium C5 (C5) induced a rapid increase
      in the cytotoxic activity of Lyt-2+ peritoneal T cells and was detected even 21
      days later. The antigen specificity of some of these cells was confirmed in
      cytotoxicity assays using P815 tumour cells infected with 11RX organisms as
      targets. No cytotoxic activity was detected in the spleen cell suspensions of
      infected (and normal) mice unless the cells were first activated by in vitro
      culture with concanavalin A (Con A). Both types of activated spleen cells showed
      LDCC but Salmonella-specific cytotoxic Lyt-2+ T cells were detected only in
      spleen cell (SC) cultures prepared from mice challenged with a second dose of
      Salmonella.

PMID- 7512526
TI  - Synergistic stimulation of human B lymphocytes by anti-CD40 monoclonal antibodies
      and synthetic lipopeptide analogues from Escherichia coli lipoprotein.
AB  - Human tonsillar B lymphocytes were stimulated with synthetic lipopeptide
      analogues of Escherichia coli lipoprotein alone or together with anti-CD40 and/or
      interleukin-4 (IL-4). While lipopeptides alone or lipopeptides plus IL-4 did not
      include proliferation of B lymphocytes, synergistic stimulation was observed when
      anti-CD40 antibodies were added. Proliferation was even more pronounced in the
      presence of Fc receptor type II (FcRII)-transfected L cells. Compared to the
      stimulus anti-CD40 plus IL-4 plus FcRII-transfected fibroblasts exerted, the
      addition of lipopeptides induced a more rapid maximal response which peaked on
      day 4. Antibody production could also be enhanced by lipopeptides. Our data
      provide evidence that lipopeptides, which act as mitogens toward murine B
      lymphocytes, also stimulate human B lymphocytes, provided that co-signals are
      added.

PMID- 7512525
TI  - Detection of Salmonella-specific L3T4+ and Lyt-2+ T cells which can proliferate
      in vitro and mediate delayed-type hypersensitivity reactivity.
AB  - This study was based on an initial observation that, although culture of T cells
      from Salmonella-infected mice with concanavalin A induced both L3T4+ T cells and
      Lyt-2+ T cells to proliferate, there was a relative increase in the
      responsiveness of the Lyt-2+ T cells in suspensions harvested from mice with
      secondary infection. Accordingly, primed T cells, obtained from the peritoneal
      cavities and spleens of mice that had received one or two intraperitoneal doses
      of Salmonella were examined for the presence of antigen-specific, class I major
      histocompatibility complex (MHC)-restricted Lyt-2+ T cells. After primary
      infection with avirulent Salmonella enteritidis 11RX (11RX) only L3T4+ T cells
      could be induced to proliferate in response to formalin-killed 11RX organisms,
      and a second dose of live 11RX did not change the phenotype of the responding T
      cell population. In contrast, secondary challenge with S. typhimurium C5 (C5)
      generated cell populations where both L3T4+ and Lyt-2+ T cells proliferated when
      cultured with formalin-killed 11RX. Transfer of delayed-type hypersensitivity
      (DTH) using mixtures of primed T cells and either killed or live Salmonella
      organisms demonstrated that DTH was mediated by L3T4+ T cells, and secondary
      infection with either the 11RX or C5 strain did not change this result. However,
      antigen-specific Lyt-2+ T cells which mediated DTH reactivity were detected using
      a Salmonella-infected cell line which expressed MHC-coded class I but not class
      II products. These Lyt-2+ T cells were present in the spleen and peritoneal
      cavity after secondary infection and in the peritoneal cavity late after a
      primary infection with 11RX.

PMID- 7512528
TI  - Expression of the IL-1 receptor discriminates Th2 from Th1 cloned CD4+ T cells
      specific for Plasmodium chabaudi.
AB  - The expression of selected interleukin receptors by cloned CD4+ T cells specific
      for the murine malaria parasite Plasmodium chabaudi chabaudi (P. chabaudi)
      representative of the T-helper (Th) 1 and Th2 subsets was examined. Both sets of
      clones expressed receptors for those interleukins for which they had a growth
      factor requirement in vitro. Each Th1 clone expressed receptors for, and was
      responsive to, interleukin (IL)-2 and IL-4, while each Th2 clone expressed
      receptors for, and was responsive to, IL-2, IL-4 and IL-1. IL-1 receptor (IL-1R)
      expression by the Th1 clones was either negligible or could not be detected. The
      disparity in expression of IL-1R by the Th1 and Th2 clones was more clear-cut
      than has been previously reported and IL-1R provided a definitive phenotypic
      marker for clones of the Th2 subset. Should IL-1R expression prove to be a
      feature of other Th2 cells cultured long-term in vitro, this will be invaluable
      for investigations involving the phenotyping, depletion or selection of CD4+ T
      cells of either Th1 or Th2 subset.

PMID- 7512529
TI  - Stimulation of human IgE production by a subset of anti-CD21 monoclonal
      antibodies: requirement of a co-signal to modulate epsilon transcripts.
AB  - CD21, the receptor for Epstein-Barr virus (EBV) and the complement receptor-2
      (CR2), was recently found to interact specifically with CD23, a low-affinity
      receptor for IgE, and to regulate IgE production. Therefore, the effect of
      different anti-CD21 monoclonal antibodies (mAb) on IgE synthesis by blood
      mononuclear cells was investigated. One anti-CD21 mAb, BU-33, was able to
      increase significantly (more than threefold) interleukin-4 (IL-4)-induced IgE
      synthesis, whereas HB-5, OKB-7 and B2 anti-CD21 mAb had no effect. BU-33 had no
      effect on IgG and IgA production and produced only a moderate increase in IgM
      production. Recombinant, 29,000 MW, soluble CD23 (sCD23) expressed in COS cells
      exhibited the same IgE-enhancing activity. BU-33 was the best inhibitor of CD23
      liposome binding to the CD21-positive cell line RPMI-8226 when compared to the
      other anti-CD21 mAb tested. BU-33 identified a different epitope on CD21. The
      effect of BU-33 on IgE production by purified tonsillar B cells and highly
      purified germinal centre B cells, was dependent on the presence of T cells or
      anti-CD40 mAb stimulation. Molecular analysis revealed that BU-33 alone failed to
      induce germline epsilon mRNA but increased the IL-4-induced germline epsilon
      transcription levels. Moreover, BU-33 had a synergistic effect on anti-CD40 mAb
      or T-cell-induced productive epsilon transcript expression. These results
      therefore indicate that the CD23-CD21 interaction needs a co-signal for B-cell
      differentiation towards IgE production.

PMID- 7512527
TI  - Differential induction of nitric oxide synthase in various organs of the mouse
      during endotoxaemia: role of TNF-alpha and IL-1-beta.
AB  - BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS)
      developed lethal septic shock. This was accompanied by significantly elevated
      concentrations of nitrite and nitrate in the plasma and expression of high levels
      of nitric oxide (NO) synthase activity in the lungs, heart, spleen and peritoneal
      macrophages. Mice pretreated with anti-tumour necrosis factor-alpha (TNF-alpha)
      monoclonal antibody or anti-interleukin-1 beta (IL-1 beta) polyclonal antibody
      were protected, in a dose-dependent manner, from endotoxin-induced mortality.
      This effect was accompanied by a significant reduction in plasma levels of
      nitrite and nitrate. Antibody treatment also reduced the level of NO synthase
      activity in peritoneal macrophages, spleen and heart but had no effect on enzyme
      expression in the lung. These results demonstrate that TNF-alpha and IL-1 beta
      play an important role in the induction of NO following administration of LPS and
      in the development of endotoxin-induced shock. In addition, NO synthase activity
      is differentially expressed in various organs and this may not always require TNF
      alpha and IL-1 beta.

PMID- 7512530
TI  - Langerhans' cell expression of the selectin ligand, sialyl Lewis x.
AB  - Cellular adhesion molecules play a central role in leucocyte migration through
      peripheral blood and tissues. A crucial stage in these events in selectin
      mediated adhesion involving E-selectin expressed on activated endothelium
      interacting with a range of carbohydrate ligands expressed by specific
      subpopulations of leucocytes. As such mechanisms may be relevant to bone marrow
      derived dendritic epidermal Langerhans' cell (LC) migration, expression of these
      carbohydrate ligands was assessed immunocytochemically in whole skin biopsies and
      in epidermal cell suspensions obtained from adult humans. Double-labelling
      experiments revealed that sialyl Lewis x, recognized by the monoclonal antibody
      CSLEX1, was expressed on epidermal LC (n = 9). Furthermore, expression was
      enhanced at 24 hr following epicutaneous application of antigen and in the
      inflammatory disorder psoriasis (n = 10). E-selectin was concomitantly strongly
      expressed on dermal endothelium in psoriasis and allergic contact dermatitis.
      Intradermal injection of the T-cell-derived cytokine interferon-gamma (IFN-gamma)
      led to increased LC expression of sialyl Lewis x. In epidermal cell suspensions,
      in contrast to keratinocytes, CD1a+ cells expressed sialyl Lewis x, intensity of
      which was enhanced after 4 days in culture. CSLEX1 staining could be abolished
      and CD15 (non-sialated Lewis x) expression induced by saponification and
      treatment with neuraminidase. Expression of other selectin ligands was also
      examined. While the cutaneous lymphocyte antigen defined by the monoclonal
      antibody HECA-452 reacted with a small minority of LC, sialyl Lewis a and
      sulphatide were not expressed under any experimental conditions. These studies
      indicate that E-selectin-sialyl Lewis x interactions are potentially important in
      LC migration, both into and out of skin.

PMID- 7512532
TI  - Characterization of a novel leucocyte surface membrane antigen recognized by the
      monoclonal antibody WM65.
AB  - WM65 is a murine mAb which recognizes a novel surface membrane antigen present on
      leukaemic and normal leucocytes. The present study further investigates the
      nature of this antigen, especially those features which relate to the possible
      therapeutic applications of the WM65 antibody. There are 1-3 x 10(4) molecules of
      this antigen present on normal leucocytes, and the same or greater numbers of
      antigen molecules are present on a variety of leukaemic cells. In vitro data
      showed that the WM65 antibody is internalized following interaction with its
      antigen on normal leucocytes. The affinity of this antibody was calculated using
      an ELISA method which required neither labelling of the antibody nor purification
      of the antigen and the affinity constant was found to be 3 x 10(7) +/- 2 x 10(7)
      (mol/L)-1. Further data are presented which suggest that this antigen is a
      differentiation antigen and an integral membrane protein. Despite the relatively
      low affinity of the WM65 antibody, a number of characteristics of the antigen
      suggest the antibody may possibly have therapeutic applications. These
      characteristics include its cellular distribution, the number of antigen
      molecules expressed on the cell surface and its ability to internalize in vitro.

PMID- 7512533
TI  - Production and characterization of mouse thymic epithelial cell clones.
AB  - Four thymic epithelial cell lines (TEC) were derived from neonatal CBA and non
      obese diabetic (NOD) mouse thymus. From these cell lines a series of clones were
      produced by limit dilution and these have remained in stable culture for more
      than 1 year. Morphological characterization indicates that most cells are
      stellate with numerous short or long processes and ultrastructural studies show
      both active and quiescent cells with junctional complexes and bundles of
      tonofibrils. Immunohistochemical and flow cytometric analyses show that the cells
      express cytokeratin and appear to label for markers characteristic of cortical
      epithelial cells. Most clones express Thy-1, Pgp-1, ICAM-1, HSA and B220 antigen,
      but are negative for LFA-1, CD2, Mel 14, Fc receptor, Mac-1, CD4 and CD8. All
      clones express low to moderate levels of class I MHC but are either negative or
      extremely low for class II MHC antigen. Most clones secrete IL-6 and granulocyte
      macrophage-CSF (GM-CSF) in vitro, but generally do not produce IL-2, IL-3, IL-4
      or IFN-gamma.

PMID- 7512531
TI  - Isolation and characterization of a cartilage-specific membrane antigen (CH65):
      comparison with cytokeratins and heat-shock proteins.
AB  - We report the isolation and characterization of a 65,000 MW chondrocyte
      autoantigen (CH65) which may be involved in rheumatoid arthritis. This
      chondrocyte-specific antigen reacted with sera from patients with rheumatoid
      arthritis (RA). CH65 did not cross-react with a polyclonal antibody raised
      against microbial heat-shock protein (hsp) 65, anti-human hsp 65 monoclonal
      antibodies (mAb) (LK1 and LK2), anti-microbial hsp 65 mAb (IA10, IIC8 and WTB
      78H1) and anti-cytokeratin 8, 18, 19 mAb (NCL5D3MAb). CH65 could be purified from
      chicken chondrocyte membranes by ammonium sulphate precipitation and a novel
      electro-gel-filtration method. The amino acid analysis yielded an unusually high
      degree of glycine, serine and asparagine residues. The internal amino acid
      sequence obtained by tryptic digestion revealed homologies with the cytokeratin
      family. Despite these homologies, CH65 lacked immunological cross-reactivity with
      commercial anti-cytokeratin antibodies. Mice mAb generated against the purified
      CH65 (C6) were used to identify the protein as a tissue-specific constitutive
      protein membrane from chondrocytes. Sera from patients with RA cross-reacted with
      purified CH65. The stress or heat-shock protein (hsp 65), implicated in the
      development of experimental and clinical arthritis, showed no immunological cross
      reactivity with CH65 in Western blots. These findings suggest that CH65 may
      represent an interesting cartilage-specific new antigen in RA. The availability
      of this antigen in purified form and specific mAb may offer useful tools in
      arthritis research.

PMID- 7512534
TI  - Cyclic regulation of B220 antigen expression in immature B cell lines.
AB  - Three independent immature B cell lines transformed with temperature-sensitive
      mutants of Abelson murine leukaemia virus (A-MuLV) persistently expressed B220
      antigen detected by both of the anti-B220 antibodies RA3-6B2 and 14.8 during
      culture at the permissive temperature (35 degrees C). RA3-6B2 recognizes the B220
      eptiope and that 14.8 is a CD45RA antibody. However, when the culture temperature
      was shifted up to the non-permissive temperature (39 degrees C) and the culture
      was continued for 2-3 weeks, a population of the cells (RA3-6B2-14.8+ cells) that
      lost RA3-6B2 antigen appeared in all three cell lines. From these populations,
      RA3-6B2-14.8+ subclones were independently isolated by limiting dilution and the
      phenotype was stable during culture at the permissive temperature. When the
      culture temperature of the RA3-6B2-14.8+ subclones was shifted up to the non
      permissive temperature and the culture was continued for 2-3 weeks, RA3-6B2
      antigen was re-expressed in a subpopulation of the RA3-6B2-14.8+ cells. These
      results demonstrated cyclic regulation of B220 antigen expression during
      proliferation and/or differentiation of immature B cell lines.

PMID- 7512535
TI  - The migration of Langerhans' cells into and out of lymph nodes draining normal,
      carcinogen and antigen-treated sheep skin.
AB  - Epidermal Langerhans' cell (LC) migration to the regional lymph node and beyond
      into central lymph was examined in sheep following topical application of the
      complete chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) or the contact
      sensitizing antigen 2,4,6-trinitrochlorobenzene (TNCB). This was facilitated by
      cannulating previously constructed pseudoafferent lymphatic vessels draining the
      skin treated with these agents or alternatively, the efferent lymphatic vessel of
      the regional lymph node. Application of DMBA resulted in a biphasic increase in
      LC migration. There was an initial increase in LC migration at 25 h with the
      maximum response (3.6 x 10(7) LC/h) occurring approximately 5 days after DMBA
      treatment. In contrast, the contact sensitizing antigen TNCB caused enhanced LC
      migration within minutes of the application of antigen (3.3 x 10(6) LC/h) and
      peak migration at 8-12 h. Examination of efferent lymph cells from the regional
      lymph node after DMBA treatment showed uncharacteristically large numbers of LC
      traversing the lymph node. These LC migration patterns suggest different
      mechanisms may trigger the migration of LC from skin after the application of
      DMBA to those associated with the normal processes of antigen presentation.

PMID- 7512536
TI  - Arachidonic acid metabolism in benign and malignant prostatic tissue in vitro:
      effects of fatty acids and cyclooxygenase inhibitors.
AB  - Concentrations of fatty acids (FA) in prostatic tissue of patients with either
      benign or malignant prostatic disease have previously been shown to be
      significantly different. In particular, there was a significant reduction in
      arachidonic acid (AA, C20:4n-6) and docosapentaenoic acid (DPA, C22:5n-6)
      concentrations in malignant prostatic tissue (PCa) phospholipids (PL). It was
      suggested that the decreased AA concentration in PCa may be due to its increased
      metabolism via the cyclooxygenase (CO) and/or lipoxygenase (LO) pathways to
      produce eicosanoids such as prostaglandins (PGs) and/or leukotrienes (LTs) rather
      than an impairment in desaturase activity in situ. The eicosanoid production in
      benign prostatic tissue (BPH) and PCa was determined using [3H]AA. The only
      eicosanoid produced in significant amounts by either tissue was PGE2 and PCa
      converted radiolabelled AA to PGE2 at an almost 10-fold higher rate than BPH.
      PGE2 production from [3H]AA by PCa was investigated in the presence of oleic acid
      (OA, C18:1n-9), eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA,
      C22:6n-3), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosatetraynoic acid
      (ETYA) and ketoprofen (KPN) respectively. OA was found to be the most effective
      inhibitor of PGE2 production by PCa compared with DHA, EPA, ETYA and KPN, while
      DGLA was the least effective. Diacylglycerol (DAG) formation from labelled AA by
      PCa was about 4-fold greater than in BPH. Such high levels of DAG may be a means
      of promoting tumorigenesis through activation of protein kinase C as found with
      phorbol esters which can be regarded as DAG analogues.

PMID- 7512537
TI  - Characterization of monoclonal antibody PAM4 reactive with a pancreatic cancer
      mucin.
AB  - A monoclonal antibody (MAb), PAM4, having reactivity with pancreatic carcinoma
      has been developed. PAM4 is an IgG1 immunoglobulin produced by immunization of
      mice with mucin purified from the xenografted RIP1 human pancreatic carcinoma. An
      immunohistochemical study of normal adult tissues showed the PAM4 reactive
      epitope to be restricted to the gastrointestinal tract and absent from normal
      pancreas. In neoplastic tissue, PAM4 was reactive with 85% of the pancreatic
      carcinomas, approximately half of the colon cancers and none of the breast,
      ovarian, prostate, renal and liver cancers. PAM4 was, in general, non-reactive
      with pancreatitis specimens whereas CA19.9 and DUPAN2 were strongly reactive with
      each one. Treatment of the mucin antigen by heating, reduction of disulfide
      bonds, or protease digestion abolished immunoreactivity with PAM4. Treatment of
      the mucin by neuraminidase or periodate oxidation reduced immunoreactivity but
      did not completely abolish it. Our data are consistent with the proposal that the
      PAM4 epitope is a conformationally dependent peptide epitope and that certain
      carbohydrate structures are necessary in order to maintain the correct peptide
      conformation. The high specificity and intense reactivity of PAM4 with pancreatic
      carcinoma tissue suggests that the antibody may prove useful for in vitro
      diagnostic assays as well as in vivo targeting of diagnostic and therapeutic
      agents.

PMID- 7512538
TI  - Synthetic peptides and purified antigens as vaccines.
AB  - Molecular biology and, in particular, knowledge of the immune response at the
      molecular level provide the research community with the opportunity to design
      vaccines that will elicit the appropriate responses for many diseases. The
      critical issue is to identify the immune response that correlates with
      protection. It is remarkable how well the empirical approach has worked; it is
      essential, therefore, not to ignore the lessons to be learned from these
      successes. It is particularly essential that each disease and the immune response
      that affords protection be studied individually so that the appropriate responses
      can be induced.

PMID- 7512539
TI  - A phase I trial of fazarabine in refractory pediatric solid tumors. A Pediatric
      Oncology Group study.
AB  - Fazarabine is a synthetic analog of cytosine arabinoside and 5-azacytidine that
      incorporates structural features of both compounds. Xenograft studies showed good
      activity against a variety of transplanted tumors. Initial studies in adults
      employed both a continuous infusion schedule and a daily bolus x 5 schedule.
      Myelotoxicity, especially neutropenia, was dose-limiting, with excessive
      myelotoxicity seen on the daily bolus x 5 at 72 mg/M2/day. Since short infusions
      may be administered in Ringer's lactate rather than either dimethylsulfoxide or
      dimethylacetamide required for continuous infusion, this study examined a daily x
      5 schedule in children with refractory solid tumors. The initial dosage was 30
      mg/M2/day, 80% of the maximum tolerated dosage in adults, with subsequent 30%
      dosage escalations. A total of 18 patients were enrolled, with a wide spectrum of
      pediatric solid tumors. Myelosuppression was the only significant toxicity, and
      was excessive at 78 mg/M2/day. Therefore, on this bolus regimen, 65 mg/M2/day for
      5 days was the maximum tolerated dosage. One patient with medulloblastoma had
      stable disease for 65 days. No other responses were seen.

PMID- 7512540
TI  - Magnetometric evaluation of the effects of gallium arsenide on the clearance and
      relaxation of iron particles.
AB  - Intratracheal instillation of GaAs suspension has been histopathologically shown
      to induce a diffuse pulmonary response. In the present study, magnetometry was
      used to evaluate the effects of intratracheally instilled GaAs on the behavior of
      externally magnetized iron particles instilled in rabbit lung. Magnetometric
      evaluation of the effects of GaAs in rabbits dosed with 30 mg or 300 mg/animal
      showed significant decreased relaxation of iron particles at 1, 3, 7, 14, 21 and
      28 days following instillation compared with the controls. Relaxation indicates a
      rapid decrease of remanent magnetic field following magnetization of the lungs
      due to random rotation of phagocytized iron particles in macrophages. Clearance
      of the iron particles was measured by serial determinations of the remanent
      magnetic field at the end of magnetization estimated from relaxation curves.
      Clearance was significantly impaired in rabbits exposed to both doses of GaAs at
      14, 21 and 28 days after instillation. Dose-effect relationships were observed in
      both cases. Histological examination of lungs instilled with these doses
      indicated active phagocytosis of GaAs and iron particles by alveolar macrophages.

PMID- 7512542
TI  - Coexpression of different cytokeratins, vimentin and desmin in the rete testis
      and epididymis in the dog.
AB  - The expression patterns of low and high molecular weight cytokeratins (LCK and
      HCK) vimentin and desmin were investigated by immunocytochemistry in the rete
      testis and epididymis in the dog. The epithelium of the rete testis displayed
      coexpression of LCK, vimentin and desmin. The epithelium of the efferent ductules
      was composed of ciliated and nonciliated cells; the ciliated cells expressed LCK
      strongly. The epithelium of the epididymal duct was composed of principal, apical
      and basal cells. Principal cells in the duct of the head of the epididymis
      displayed LCK and vimentin, with a predominance of LCK in the apical cytoplasmic
      regions and vimentin in the basal portions of the cells. Expression of vimentin
      in the principal cells decreased towards the body of the epididymis and
      disappeared in the tail region, where LCK remained unchanged. Apical cells of the
      epididymal duct expressed LCK. Basal cells in the duct of the head and body of
      the epididymis showed LCK and those of the duct of the body of the epididymis
      also HCK expression.

PMID- 7512543
TI  - New applications for the zinc iodide-osmium tetroxide technique.
AB  - The zinc iodide-osmium tetroxide (ZIO) fixation/staining method was applied for
      neurocytological studies and also to examine several other tissue samples
      including epidermal Langerhans cells, blood and bone marrow cells and lymphoid
      tissue. Although precise specificity cannot be attributed to the staining
      reaction, interesting staining patterns for different cell types were observed by
      using one of the ZIO staining solutions. The significance of ZIO positivity is
      briefly discussed.

PMID- 7512544
TI  - Labelling of neurons in the rat superior cervical ganglion after injection of
      wheat-germ agglutinin-horseradish peroxidase into the contralateral ganglion:
      evidence of transneuronal labelling.
AB  - Recent studies have shown that injection of the tracer wheat-germ agglutinin
      horseradish peroxidase (WGA-HRP) into the superior cervical ganglion (SCG) of one
      side results in labelling of neurons in the contralateral SCG and the stellate
      ganglion. This study was designed to verify whether or not bilateral projections
      from the superior cervical ganglion to the midline structures, particularly to
      the pineal gland, play a role in the transport of WGA-HRP to the contralateral
      SCG. One group of rats received WGA-HRP injection into the right SCG (group I).
      Four groups of rats underwent the following operations prior to the injection of
      WGA-HRP into the right superior cervical ganglion: transection of the external
      carotid nerve (group II), transection of the internal carotid nerve (group III),
      transection of the external carotid nerve combined with pinealectomy (group IV),
      transection of both the internal and the external carotid nerves (group V). The
      mean number of labelled neurons in the left SCG of each group were found as
      follows: group I, 1516 +/- 221 (mean +/- S.D.); group II, 861 +/- 122; group III,
      543 +/- 99; group IV, 562 +/- 144; group V, 220 +/- 52. The results of this study
      suggest that the contralateral labelling depends on the transneuronal transport
      of WGA-HRP through the terminal fields of innervation of the midline structures
      that receive bilateral projections from both SCGs.

PMID- 7512541
TI  - Development of the chick thymus microenvironment: a study by lectin
      histochemistry.
AB  - The microenvironment of the chick thymus has been examined during development
      using lectin histochemistry. We have assayed WGA, Con A, RCA-I and TPA on thymic
      sections from 13, 15, 17 and 19 d chick embryos and 0, 5, 10 and 15 d chicks. All
      lectins were immunoperoxidase and colloidal gold-conjugated for transmission
      electron microscope observations. WGA labelled both the cortical and medullary
      thymic stroma at all the stages analysed. An intense reaction to WGA was observed
      in the subcortical region from stage 18 embryos to 5 d chicks. On the other hand,
      WGA did not stain medullary areas of the chick thymus. Con A lectin detected
      several cell clusters of stromal cells and thymocytes in cortical regions. These
      clusters could represent a lymphostromal complex with which Con A receptors are
      associated, probably in relation to cell adhesion. The residues detected by RCA
      were distributed both in stromal cells and thymocytes of the developing chick
      thymus. There was an increase of the reaction to RCA between the 19 d embryos and
      the 5 d chicks. This increase might be interpreted in terms of the secretion of
      thymic humoral factors at these stages. The thymic stromal cells stained with
      immunoperoxidase conjugated-TPA showed a reticular pattern in the medulla. There
      is a possibility that the fucosyl residues may be expressed in the Ia antigen as
      has previously been suggested in other species.

PMID- 7512545
TI  - Skeletal muscle growth and protein turnover in neonatal boars and barrows.
AB  - The objective of this study was to determine the effect of castration, within 24
      h after birth, on skeletal muscle growth and protein metabolism in neonatal pigs
      at 1, 2, and 4 wk of age. Four additional pigs were slaughtered at birth to
      obtain initial body composition. All other pigs were infused with [14C]tyrosine
      for 6 h before slaughter to determine in vivo fractional protein synthesis rates
      (FSR). At slaughter, muscle bundles were removed from the semitendinosus and
      incubated with [3H]tyrosine to determine in vitro protein synthesis rates.
      Nucleic acids and protein were determined on the semitendinosus muscle.
      Testosterone concentrations, determined at weekly intervals, peaked in boars at 3
      wk of age. Castration at birth did not affect combined weights of the
      semitendinosus, longissimus, triceps brachii, and brachialis muscles. Likewise,
      neither in vitro protein synthesis rates nor in vivo FSR were affected by
      castration. However, a developmental decline in in vivo FSR and in vitro protein
      synthesis rates occurred from 1 to 4 wk. Neither concentrations nor total
      quantity of protein, RNA, or DNA in the semitendinosus muscle differed between
      neonatal boars and barrows at any age. Concentrations of DNA and RNA at 4 wk were
      two- and threefold lower, respectively, than at birth. Protein:DNA and
      protein:RNA ratios increased three- and sixfold, respectively, from birth to 4
      wk. Testosterone concentrations had little effect on skeletal muscle growth and
      protein turnover rates during this neonatal period.

PMID- 7512547
TI  - Susceptibility of Pseudomonas pseudomallei to some newer beta-lactam antibiotics
      and antibiotic combinations using time-kill studies.

PMID- 7512546
TI  - Diet effects and ontogeny of alterations of circulating insulin-like growth
      factor binding proteins in newborn dairy calves.
AB  - Insulin-like growth factors (IGF) are important growth regulators in many
      species, and their effects are influenced by their association with IGF-binding
      proteins (IGFBP). The objectives of this study were to characterize the ontogeny
      of the blood plasma IGFBP in calves and to determine the effect of dietary IGF-I
      neonatal plasma IGFBP. Plasma from newborn and 7-d-old male calves fed milk
      replacer, milk replacer + recombinant human IGF-I (rhIGF-I), or colostrum for 2 d
      followed by milk replacer was analyzed for IGFBP by ligand blot analysis. In
      addition, plasma samples from 1-, 12-, 24-, and 45-wk-old male calves were
      analyzed for IGFBP and IGF-I. Newborn and 7-d-old calf plasma contained IGFBP
      with M(r) of 26, 34, and 42 to 48 kDa. These profiles were not affected by the
      dietary treatments; however, a slight increase in the 34-kDa IGFBP and a slight
      decrease in the 26- and 42- to 48-kDa IGFBP were detected from birth to 7 d of
      age. The 34-kDa was confirmed to be bovine IGFBP-2 by immunoblot and the 42- to
      48-kDa is likely IGFBP-3. The 29-, 31-, and 42- to 48-kDa IGFBP increased between
      1 and 45 wk of age. Similarly, plasma IGF-I concentrations were increased from
      49.7 to 449.7 ng/mL in plasma from calves from 1 to 45 wk of age. In contrast,
      the 34-kDa IGFBP increased from 1 to 12 wk but then gradually decreased from 12
      to 45 wk, whereas the 26-kDa IGFBP did not change.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7512548
TI  - Client education: or how to make the client a partner.

PMID- 7512549
TI  - The changing world of images.

PMID- 7512550
TI  - Phenotypic suppression of DNA gyrase deficiencies by a deletion lowering the gene
      dosage of a major tRNA in Salmonella typhimurium.
AB  - One of the pleiotropic phenotypes of mutations affecting DNA gyrase activity in
      Salmonella typhimurium is the constitutive deattenuation of the histidine operon.
      In the present work, we isolated and characterized a suppressor mutation which
      restores his attenuation in the presence of a defective gyrase. Such a
      suppressor, initially named sgdA1 (for suppressor gyrase deficiency), was found
      to correct additional phenotypes associated with defective gyrase function. These
      include the aberrant nucleoid partitioning of a gyrB mutant and the conditional
      lethality of a gyrA mutation. Furthermore, the sgdA1 mutation was found to confer
      low-level resistance to nalidixic acid. The last phenotype permitted isolation of
      a number of additional sgdA mutants. Genetic analysis established the recessive
      character of these alleles as well as the position of the sgdA locus at 57 U on
      the Salmonella genetic map. All of the sgdA mutants result from the same
      molecular event: a deletion removing three of the four tandemly repeated copies
      of argV, the gene which specifies tRNA(2Arg), the major arginine isoacceptor
      tRNA. These findings, combined with the observation of some Sgd-like phenotypes
      in a tRNA modification mutant (hisT mutant), lead us to propose that protein
      synthesis contributes, directly or indirectly, to the pathology of gyrase
      alterations in growing bacteria. We discuss plausible mechanisms which may be
      responsible for these effects.

PMID- 7512551
TI  - Tn10-mediated inversions fuse uridine phosphorylase (udp) and rRNA genes of
      Escherichia coli.
AB  - Two strains carrying metE::Tn10 insertions (upstream of the udp gene) were used
      to isolate mutants of Escherichia coli overexpressing udp. These strains differ
      in their gene order; one contains an inversion between the rrnD and rrnE rRNA
      operons. Selection was based on the ability of overexpressed Udp to complement
      thymine auxotrophy. Chromosomal rearrangements that connect the udp gene and
      promoters of different rrn operons were obtained by this selection. Seven of 14
      independent mutants selected in one of the initial strains contained similar
      inversions of the metE-rrnD segment of the chromosome (about 12% of its length).
      Another mutant contained traces of a more complicated event, inversion between
      rrnB and rrnG operons, which was followed by reinversion of the segment between
      metE and the hybrid rrnG/B operon. Similar inversions (udp-rrn) in a strain
      already carrying an rrnE-rrnD inversion flip the chromosomal segment between metE
      and rrnD/E in the opposite direction. In this case, inversions are also
      accompanied by duplications of the chromosomal region between the rrnA and hybrid
      udp-rrnD/E operons. PCR amplification with a set of oligonucleotides from the
      rrn, Tn5, and met genes was used for more detailed mapping. Amplified fragments
      of the rearranged chromosomes connecting rrnD sequences and insertion elements
      were sequenced, and inversion endpoints were established.

PMID- 7512552
TI  - Hypervariable region IV of Salmonella gene fliCd encodes a dominant surface
      epitope and a stabilizing factor for functional flagella.
AB  - To identify the major antigenic determinant of native Salmonella flagella of
      antigenic type d, we constructed a series of mutated fliCd genes with deletions
      and amino acid alterations in hypervariable region IV and in region of putative
      epitopes as suggested by epitope mapping with synthetic octameric peptides (T.M.
      Joys and F. Schodel, Infect. Immun. 59:3330-3332, 1991). The expressed product of
      most of the mutant genes, with deletions of up to 92 amino acids in region IV,
      assembled into functional flagella and conferred motility on flagellin-deficient
      hosts. Serological analysis of these flagella with different anti-d antibodies
      revealed that the peptide sequence centered at amino acids 229 to 230 of
      flagellin was a dominant B-cell epitope at the surface of d flagella, because
      replacement of these two amino acids alone or together with their flanking
      sequence by a tripeptide specified by a linker sequence eliminated most
      reactivity with antisera against wild-type d flagella as tested by enzyme-linked
      immunosorbent assay or by Western immunoblot. Functional analysis of the mutated
      flagellin genes with or without an insert suggested that amino acids 180 to 214
      in the 5' part of hypervariable region IV (residues 181 to 307 of the total of
      505) is important to the function of flagella. The hybrid proteins formed by
      insertion of peptide sequence pre-S1 12-47 of hepatitis B virus surface antigen
      into the deleted flagellins assembled into functional flagella, and antibody to
      the pre-S1 sequence was detected after immunization of mice with the hybrid
      protein. This suggests that such mutant flagellins containing heterologous
      epitopes have potential as vaccines.

PMID- 7512553
TI  - Induction of surfactin production in Bacillus subtilis by gsp, a gene located
      upstream of the gramicidin S operon in Bacillus brevis.
AB  - The deduced amino acid sequence of the gsp gene, located upstream of the 5' end
      of the gramicidin S operon (grs operon) in Bacillus brevis, showed a high degree
      of similarity to the sfp gene product, which is located downstream of the srfA
      operon in B. subtilis. The gsp gene complemented in trans a defect in the sfp
      gene (sfpO) and promoted production of the lipopeptide antibiotic surfactin. The
      functional homology of Gsp and Sfp and the sequence similarity of these two
      proteins to EntD suggest that the three proteins represent a new class of
      proteins involved in peptide secretion, in support of a hypothesis published
      previously (T. H. Grossman, M. Tuckman, S. Ellestad, and M. S. Osburne, J.
      Bacteriol. 175:6203-6211, 1993).

PMID- 7512555
TI  - The substituted benzimidazolone NS004 is an opener of the cystic fibrosis
      chloride channel.
AB  - Cystic fibrosis is a major inherited disorder involving abnormalities of fluid
      and electrolyte transport in a number of different organs. Epithelial cells of
      cystic fibrosis patients have a decreased capacity to secrete chloride in
      response to cAMP-mobilizing agents because of the mutation of a single gene. The
      gene product, the cystic fibrosis transmembrane conductance regulator or CFTR, is
      a chloride channel. The most frequent mutation is a deletion of phenylalanine in
      position 508 (delta F508-CFTR) that reduces both the expression of the CFTR
      protein at the cell surface, and the activity of the Cl- channel. This work
      presents the properties of NS004, a substituted benzimidazolone, which is the
      first activator of normal and mutant CFTR-associated chloride channels to be
      described. NS004 activated CFTR and delta F508-CFTR Cl- channels expressed in
      Xenopus oocytes, and increased 125I efflux (via the Cl- channel) from Vero cells
      expressing CFTR and delta F508-CFTR. Application of NS004 to the external side of
      outside-out patches excised from these CFTR- and delta F508-CFTR-expressing cells
      induced a marked and reversible increase in channel activity.

PMID- 7512554
TI  - Processing and surface presentation of the Mycoplasma hyorhinis variant
      lipoprotein VlpC.
AB  - The variant surface lipoprotein VlpC of Mycoplasma hyorhinis was shown to be
      processed by cleavage of a characteristic prokaryotic prolipoprotein signal
      peptide. In addition, a vlpC::phoA fusion protein expressed and translocated in
      Escherichia coli was recognized by surface-binding monoclonal antibodies, which
      identified the characteristic region II of Vlps, containing divergent external
      sequences proximal to the membrane, as an exposed portion of these surface
      proteins subject to immune recognition and selection.

PMID- 7512556
TI  - Defective asialoglycoprotein receptor endocytosis mediated by tyrosine kinase
      inhibitors. Requirement for a tyrosine in the receptor internalization signal.
AB  - Regulated endocytosis by growth factor receptors requires intact receptor
      associated tyrosine kinase activity. To determine whether a similar requirement
      exists for the asialoglycoprotein (ASGP) receptor which lacks intrinsic tyrosine
      kinase activity and participates in constitutive endocytosis, we examined the
      effect of three tyrosine kinase inhibitors, tyrphostin, genistein, and
      staurosporine, on receptor-mediated endocytosis in the human hepatoma line HepG2.
      These compounds inhibited early receptor internalization from the plasma membrane
      to internal protease-resistant sites in a concentration-dependent manner. This
      effect correlated with their inhibition of tyrosine phosphorylation of the ASGP
      receptor in vitro. Receptor trafficking subsequent to receptor internalization
      was unaffected. Endocytosis of another constitutively internalized protein, the
      transferrin receptor, was also inhibited by these compounds. In contrast,
      pinocytosis of the fluid-phase marker Lucifer yellow was not inhibited. The
      tyrosine kinase inhibitors also decreased the endocytic rate of transfected ASGP
      receptor H1 subunit in SK-Hep-1 cells. Therefore an intact ASGP receptor
      heterooligomeric complex is not required for this effect. Mutation of the single
      cytoplasmic tyrosine at position 5 of the H1 subunit to phenylalanine produced an
      ASGP receptor which was endocytosed regardless of treatment with the tyrosine
      kinase inhibitors. We conclude that tyrosine kinase activity modulates the rate
      of receptor endocytosis at a point early in the internalization process.

PMID- 7512557
TI  - Structure, genomic organization, and expression of the human interleukin-8
      receptor B gene.
AB  - Two distinct receptors for the chemoattractant interleukin-8 (designated IL-8RA
      and -B) have been cloned recently. The receptors are expressed almost exclusively
      on neutrophils and myelomonocytic cell lines. In an attempt to understand the
      tissue-specific expression and to identify transcriptional regulatory elements we
      have cloned, sequenced, and characterized the human IL-8RB gene. The gene
      consists of 3 exons, interrupted by two introns of 3 and 5.4 kilobases (kb). A
      1065-base pair open reading frame is encoded entirely in the third exon. A 1.4-kb
      3'-untranslated region contains clustered AU-rich elements, similar to those
      described for genes regulated by altering mRNA stability. The start site of
      transcription was mapped by a modified rapid amplification of cDNA ends technique
      and revealed an unexpectedly long 5'-untranslated region of 423 base pairs. A
      TATA box equivalent was found in the 5'-flanking region 20 nucleotides upstream
      of the start of the first exon. The promoter was separated from the ATG
      initiation codon by 8.75 kb. Comparison of the IL-8RB promoter with the promoter
      region of the receptor for another chemoattractant ligand, the bacterial peptide
      f-Met-Leu-Phe, revealed 3 novel but conserved motifs occupying similar positions.
      The immediate 5'-flanking region was GC-rich with 3 SP-1-like and 2 AP-2 sites
      identified in close proximity to the transcription start site. This essential
      promoter region was found to be responsible for constitutive expression,
      inducible by granulocyte colony-stimulating factor and controlled by silencer
      elements located further upstream between positions -779 and -118.

PMID- 7512558
TI  - The complete primary structure for a novel laminin chain, the laminin B1k chain.
AB  - We have isolated overlapping cDNA clones encoding the entire kalinin B1 chain.
      The predicted sequences are consistent with the models proposed for the structure
      of this chain as a truncated homologue of the B1 chain of laminin. The percent
      sequence homology with other laminin B1 chains is relatively low, suggesting that
      this chain is functionally different. The sequence of the VI domain of this chain
      is consistent with the possibility that it serves to bind specifically the
      kalinin A chain and subsequently covalently binds to it. In keeping with the
      accepted nomenclature for the laminin chains we name this novel polypeptide the
      laminin B1k chain.

PMID- 7512560
TI  - External ATP and its analogs activate the cystic fibrosis transmembrane
      conductance regulator by a cyclic AMP-independent mechanism.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl- channel
      activated by protein kinase A and regulated by ATP in a complex manner. We have
      applied patch-clamp techniques to C127i mouse mammary carcinoma cells transfected
      with human CFTR to assess the role of external ATP in the modulation of CFTR
      function. Extracellular ATP was sufficient to activate non-rectifying, Cl(-)
      selective whole-cell currents in CFTR-transfected, but not mock-transfected
      cells. The ATP-mediated activation of CFTR was independent of protein kinase A
      since channel activation by ATP was preserved in cells that were (a) depleted of
      intracellular ATP, (b) incubated with the cAMP antagonist Rp-cAMPS, or (c)
      exposed to the protein kinase A inhibitor, 5-24 amide. In each of these
      conditions, 8-Br-cAMP was no longer capable of activating CFTR. The possibility
      that the extracellular ATP activation of Cl- currents in CFTR-expressing C127i
      cells was mediated by a P2-type purinergic receptor was supported by studies in
      which the effect of external ATP on the Cl- currents was mimicked by the ATP
      analogs, ATP gamma S and beta,gamma-methylene ATP, but not the uridine
      nucleotide, UTP. Single-channel analysis of ATP-activated Cl -currents under both
      cell-attached and excised, inside-out patch-clamp configurations indicated that
      this channel is only present in CFTR-transfected cells and indistinguishable from
      CFTR. External ATP also activated ATP currents in CFTR-transfected cells, a novel
      function of CFTR. These findings are consistent with the presence of a purinergic
      receptor signal transduction mechanism in C127i cells whose activation by
      external ATP is linked to the activation of CFTR in a cAMP-independent manner.
      The data provide additional support for the use of ATP and its analogs as
      alternative therapies in cystic fibrosis.

PMID- 7512562
TI  - Photoidentification of mannosyltransferases of dolichol cycle in the mammary
      gland. Purification and characterization of GDP-Man:Man beta 1-->4GlcNAc beta 1-
      >4GlcNAc-P-P-dolichol mannosyltransferase.
AB  - Glc3Man9GlcNAc2-P-P-Dol serves as the major precursor for the biosynthesis of
      asparagine-linked glycoproteins in eukaryotes. The first 5 of the 9 mannosyl
      residues during the assembly of the oligosaccharide moiety within the dolichol
      cycle in the endoplasmic reticulum are incorporated directly by the action of GDP
      Man-requiring mannosyltransferases while the remaining last 4 mannosyl residues
      are transferred by Man-P-Dol-requiring enzymes. In an earlier study (Shailubhai,
      K., Illeperuma, C., Tayal, M., and Vijay, I. K. (1990) J. Biol. Chem. 265, 14105
      14108), we identified the enzyme UDP-Glc:Dol-P glucosyltransferase by
      photolabeling rat mammary microsomes with 5-N3-[beta-32P]UDP-Glc. Applying a
      similar strategy, GDP-hexanolamine-125I-azidosalicylic acid, an analog of GDP
      Man, was found to photolabel two polypeptides of 37 and 69 kDa among the
      microsomal proteins of the rat mammary gland. A differential ammonium sulfate
      saturation (60-80%) of the detergent-solubilized microsomal proteins enriched the
      69-kDa polypeptide. Photolabeling of this polypeptide was specifically inhibited
      by guanine-containing nucleotides and nucleotide-sugars and was associated with a
      GDP-Man-requiring mannosyltransferase. The mannosyltransferase was purified
      nearly 16,000-fold and shown to contain the 69-kDa polypeptide. The purified
      enzyme catalyzes the transfer of [14C]Man from GDP-[14C]Man to Man beta 1-
      >4GlcNAc beta 1-->4GlcNAc-P-P-Dol in alpha 1,3-linkage to give [14C]Man alpha 1-
      >3Man beta 1-->4GlcNAc beta 1-->4GlcNAc-P-P-Dol as the product. Antibodies raised
      against the 69-kDa polypeptide removed the enzymatic activity from the detergent
      extract of the rat mammary microsomes and reacted specifically with a polypeptide
      band of the same size on immunoblots. The purified enzyme showed a pH optima of
      7.4-7.8, Km approximately 4 microM for GDP-Man, approximately 2-fold activation
      by phosphatidylcholine, and a strong inhibition by sulfhydryl-selective reagents,
      N-ethylmaleimide and p-chloromercuribenzoate. The availability of the highly
      purified enzyme and a monospecific antibody should allow its molecular cloning
      for investigating the regulation of the machinery for protein N-glycosylation
      upon hormonally modulated growth and differentiation of the mammary gland during
      its ontogeny.

PMID- 7512561
TI  - The interferon-induced 67-kDa guanylate-binding protein (hGBP1) is a GTPase that
      converts GTP to GMP.
AB  - hGBP1 is an interferon-induced 67-kDa protein of human cells that readily binds
      to agarose-immobilized GTP, GDP, and GMP but not to other nucleotides. We cloned
      hGBP1 cDNA into a histidine-tagging vector, produced recombinant hGBP1 with 6
      extra histidine residues at its N terminus in Escherichia coli, and purified this
      protein to near homogeneity from bacterial lysates. Purified hGBP1 hydrolyzed
      radiolabeled GTP but failed to hydrolyze ATP, UTP, or CTP at significant rates.
      Unexpectedly, the principal product of the GTP hydrolysis reaction was GMP rather
      than GDP. Although significant amounts of GDP were produced when the reaction was
      performed at 15 degrees C, GDP could not serve as substrate or as inhibitor of
      hGBP1. hGBP1 lacked guanylate cyclase and guanylyltransferase activity.
      Degradation of GTP to GMP most likely occurred via two consecutive cleavages of
      single phosphate groups, because pyrophosphate was not a reaction product, and
      because hGBP1 failed to hydrolyze GTP gamma S. In vitro modification assays with
      radiolabeled mevalonic acid and farnesyl pyrophosphate showed that the CaaX motif
      at the C terminus of hGBP1 functions as an isoprenylation signal. Thus, hGBP1 is
      a GTPase with novel biochemical properties that may be membrane-associated in
      eukaryotic cells.

PMID- 7512559
TI  - Alpha v integrins mediate the rise in intracellular calcium in endothelial cells
      on fibronectin even though they play a minor role in adhesion.
AB  - We have investigated which integrins mediate the elevation of intracellular
      calcium ([Ca2+]i) triggered by spreading of endothelial cells on fibronectin
      (FN). Specific anti-integrin monoclonal antibodies immobilized on glass surfaces
      were used as agonists to trigger cell spreading. These experiments demonstrated
      that an antibody to alpha v could induce the rise in [Ca2+]i, whereas two
      antibodies to alpha 5 beta 1 were inactive, despite their ability to induce cell
      spreading and elevation of intracellular pH. Antibodies in solution were then
      used as agonists to block association of specific integrins with FN. These
      experiments also showed that alpha v integrin(s) but not alpha 5 beta 1 mediated
      the rise in [Ca2+]i in cells spreading on FN. Adhesion assays in the presence of
      function-blocking anti-integrin antibodies and affinity chromatography on FN
      columns of surface-labeled cell extracts were carried out to characterize the
      integrins that bind to FN. Both methods showed that alpha v integrin(s) and alpha
      5 beta 1 participate in FN binding; however, the contribution from alpha v
      integrin(s) was much less than that of alpha 5 beta 1. These results demonstrate
      that two receptors for FN on the same cells can trigger distinct intracellular
      signaling pathways and, furthermore, that an integrin whose contribution to
      adhesion is barely detectable can have a major effect on cellular responses. The
      results also suggest that the specificity for activation of the calcium signaling
      pathway resides primarily in the integrin alpha subunit.

PMID- 7512563
TI  - Substitution of glutamine for arginine 1131. A newly identified mutation in the
      catalytic loop of the tyrosine kinase domain of the human insulin receptor.
AB  - We studied a patient with severe insulin resistance and a remarkable decrease in
      the in vivo autophosphorylation of the insulin receptor. Using a polymerase chain
      reaction-single strand conformation polymorphism method and direct sequencing, we
      identified a heterozygous mutation substituting Gln for Arg1131 in the putative
      "catalytic loop" of the tyrosine kinase domain of the insulin receptor gene. The
      Gln1131 mutant receptor was expressed by transfection in Chinese hamster ovary
      cells and compared with cells expressing the wild-type insulin receptor. Both
      mutant and wild-type receptors were expressed on the cell surface and displayed
      similar insulin-binding affinity. The Gln1131 mutation impaired the activity of
      the receptor tyrosine kinase and inhibited the ability of insulin to
      phosphorylate the endogenous substrate insulin receptor substrate-I. In addition,
      the Gln1131 mutant receptor exhibited diminished tyrosine-phosphorylated
      phosphatidylinositol 3-kinase and myelin basic protein kinase activities compared
      with the wild-type cells. It also demonstrated a defective mediation of the
      insulin signal stimulating 2-deoxy-D-glucose transport and thymidine
      incorporation, resistance to endocytosis, and insulin-induced down-regulation.
      Unlike a previously described mutation in the putative catalytic loop of the
      receptor that substituted Glu for Ala1135, the Gln1131 mutation retained
      proteolytic cleavage of the proreceptor into separate subunits. Our results
      demonstrate that a naturally occurring mutation (R1131Q) in the putative
      catalytic loop of the insulin receptor results in severe impairment of the
      tyrosine kinase function in our patient. In addition, our results indicate that
      Arg1131 is important for receptor-mediated insulin action in vivo and suggest
      that the amino acids constituting the catalytic loop of protein kinases may
      possess different modes in order to retain kinase function.

PMID- 7512564
TI  - Cross-linking of Fc gamma receptor to surface immunoglobulin on B cells provides
      an inhibitory signal that closes the plasma membrane calcium channel.
AB  - Stimulation of B lymphocytes by the cross-linking of surface Ig (sIg) with an
      F(ab')2 antibody fragment leads to the rapid activation of several tyrosine
      kinases. This gives rise to the activation of phospholipase C gamma (PLC gamma)
      and the generation of inositol phosphates. These, in turn, lead to a prolonged
      elevation of intracellular Ca2+ ([Ca2+]i) consisting of a rapid release of Ca2+
      from intracellular stores and a sustained influx of extracellular Ca2+. In
      contrast, co-cross-linking sIg to Fc gamma receptor (Fc gamma RII) with intact
      anti-sIg induces a much more transient increase in [Ca2+]i. Stimulation of the
      murine B cell lymphoma, A20, with F(ab')2 anti-sIgG leads to the production of
      high levels of IL-2, while co-cross-linking of sIgG with Fc gamma RII blocks this
      response. In studies reported here, we show that co-cross-linking of Fc gamma RII
      with sIg prevents the influx of extracellular Ca2+ without significantly
      affecting the tyrosine phosphorylation of substrates including PLC gamma 1, PLC
      gamma 2, and Syk or the mobilization of Ca2+ from intracellular stores. In cells
      that had been previously activated with F(ab')2 anti-IgG, co-cross-linking of sIg
      to Fc gamma RII rapidly abrogated the influx of extracellular Ca2+ by closing the
      plasma membrane Ca2+ channel. Additionally, even 2-3 h after stimulation of the
      cells with F(ab')2 fragment, addition of intact anti-IgG to the cells, or removal
      of extracellular Ca2+, markedly inhibited (> 90%) IL-2 production. These results
      indicate that co-cross-linking sIg with Fc gamma RII both prevented the opening
      of and actively closed the Ca2+ channel, and, through this mechanism, Fc gamma
      RII was able to control production of IL-2. Overall, since influx of
      extracellular Ca2+ has been found to be necessary for the proliferation and
      differentiation of B cells, Fc gamma RII may play a critical role in controlling
      these responses by regulating the opening of the Ca2+ channel.

PMID- 7512566
TI  - Regulation of immunoreactive insulin-like growth factor binding protein-6 in
      normal and transformed human fibroblasts.
AB  - Insulin-like growth factor-binding proteins (IGFBPs) have been shown to both
      potentiate and inhibit IGF bioactivity in vitro; thus, changes to the type or
      amount of IGFBPs present in the cellular environment will ultimately affect
      insulin-like growth factor action. In this study, we have investigated the
      production of immunoreactive IGFBP-6 by normal human fibroblasts (NHF) and an SV
      40-transformed human fibroblast line (AG2804). When analyzed by SDS
      polyacrylamide gel electrophoresis and immunoblotting, IGFBP-6 appeared as a
      doublet of 32-34-kDa in conditioned medium of both cell lines, with the lower
      molecular mass band predominating in the NHF cell line. Measured by a specific
      radioimmunoassay, serum-free NHF, and AG2804 cultures secreted IGFBP-6 at 1.44 +/
      0.09 and 1.23 +/- 0.08 ng/10(4) cells (mean +/- S.E.), respectively. Despite a
      relatively weak IGFBP-6 signal by ligand blot compared with IGFBP-3, the two
      proteins were secreted in similar molar concentrations by NHF. Retinoic acid
      increased IGFBP-6 by 3-fold in NHF and AG2804-conditioned media, maximal at
      approximately 100 nM retinoic acid. In contrast, IGFBP-6 production was inhibited
      by transforming growth factor-beta 1 and agents that increase intracellular cAMP
      concentrations, including dibutyryl cAMP, forskolin, isobutylmethylxanthine, and
      cholera toxin. This study indicates that IGFBP-6 has a pattern of regulation
      unique among the IGFBPs, supporting the concept of specific roles for each
      binding protein in regulating cell growth and metabolism.

PMID- 7512565
TI  - Sp1 is a critical factor for the monocytic specific expression of human CD14.
AB  - CD14 is a membrane glycoprotein expressed specifically on monocytes and
      macrophages, and its expression is markedly increased during the process of
      monocyte differentiation. In order to study CD14 gene regulation, the human CD14
      gene was cloned from a partial EcoRI digested chromosome 5 library. A 5.5
      kilobase genomic clone contained the full-length CD14 coding sequence and 4.2
      kilobases of 5'-upstream sequence. One major and one minor transcription start
      site were identified 101 and 130 base pairs (bp) upstream, respectively, from the
      protein translation start ATG. A DNA fragment containing 128 bp of upstream
      sequence had strong, monocyte-specific promoter activity in the CD14 positive
      monocytic cell line Mono Mac 6 as compared to the nonmonocytic cell lines HeLa
      and REX. Four regions in this DNA fragment interact with nuclear proteins
      isolated from monocytic cells. The Sp1 transcription factor bound to three
      different regions in the CD14 promoter. Mutation of the major Sp1 binding site (
      110 bp) decreased tissue-specific promoter activity, and these results, together
      with transactivation experiments, demonstrate that Sp1 plays a critical role in
      the tissue-specific expression of CD14 in monocytic cells. CD14 Sp1 site
      oligonucleotides bound preferentially to a 105-kDa Sp1 species, which is present
      in higher relative levels in monocytic than non-monocytic cells, suggesting that
      modification of Sp1, such as phosphorylation, may explain how the Sp1 site
      mediates monocytic specific promoter activity.

PMID- 7512567
TI  - Characterization of a 60-kilodalton substrate of the insulin receptor kinase.
AB  - A 60-kDa tyrosine-phosphorylated protein has been observed after insulin
      treatment of cells in immunoprecipitations of the GTPase-activating protein of
      Ras (called GAP) as well as the phosphatidylinositol 3-kinase. In the present
      studies, these two 60-kDa proteins have been shown to differ by limited
      proteolytic digestions as well as by immunoprecipitation with a monoclonal
      antibody. This monoclonal antibody was also utilized to show that the 60-kDa GAP
      associated protein was rapidly phosphorylated in intact cells after insulin
      stimulation and to associate with GAP only after insulin treatment of the cells.
      In addition, the 60-kDa protein was found to be phosphorylated in vitro by the
      insulin receptor. Finally, the 60-kDa protein immunoprecipitated by this antibody
      was found not to react with a polyclonal antibody directed against a 62-kDa
      tyrosine-phosphorylated GAP-associated protein previously observed in src
      transformed cells. These studies indicate that insulin stimulates the tyrosine
      phosphorylation of at least two distinct 60-kDa proteins, one that becomes
      associated with GAP and appears to be a direct substrate of the insulin receptor
      kinase and another that associates with the phosphatidylinositol 3-kinase.

PMID- 7512568
TI  - A role for the C2 domain of factor VIII in binding to von Willebrand factor.
AB  - We examined the possibility that the C2 domain, amino acid residues 2173-2332, of
      factor VIII (fVIII) contains a binding site for von Willebrand factor (vWf) to
      clarify previous data showing that some monoclonal and human inhibitor antibodies
      with epitopes in C2 prevent fVIII-vWf binding. We constructed a fusion protein,
      glutathione S-transferase-C2, which binds to immobilized vWf in a dose-dependent
      saturable fashion, suggesting that the fVIII C2 domain contains a binding site
      for vWf. This site was further localized by testing the effect of a synthetic
      peptide on fVIII-vWf binding. Peptide 2303-2332, consisting of a previously
      identified phosphatidyl-serine binding site, prevented fVIII binding to vWf,
      suggesting that the sites for fVIII binding to vWf or phosphatidylserine have
      some overlap. The effect of anti-C2 domain antibodies further supported these
      observations. The inhibition of fVIII binding to vWf by monoclonal antibody NMC
      VIII/5 IgG or F(ab)'2 (epitope within residues 2170-2327) and by inhibitor
      antibody MU IgG or Fab' (epitope within residues 2248-2312) was demonstrated by a
      fluid-phase binding assay and enzyme-linked immunosorbent assay. Two monoclonal
      antibodies with epitopes within amino acid residues 2170-2218 or 2248-2285, which
      do not overlap the phosphatidylserine binding site, did not have any inhibitory
      effect. Our data suggest that the previously described antagonistic binding of
      vWf and phospholipid to fVIII is due to the involvement of some C2 domain amino
      acids in both processes.

PMID- 7512569
TI  - Fibroblast growth factor receptor (FGFR) 3. Alternative splicing in
      immunoglobulin-like domain III creates a receptor highly specific for acidic
      FGF/FGF-1.
AB  - Fibroblast growth factors (FGF) regulate the growth and differentiation of cells
      through complex combinatorial signaling pathways. There are nine ligands that
      interact with a family of four tyrosine kinase FGF receptors (FGFR). Diversity in
      FGF signaling is determined in part by the affinity of specific ligand-receptor
      pairs. Alternative splicing in the FGFR ligand binding domain generates
      additional receptor isoforms with novel ligand affinities. For example, splicing
      events in the ligand binding domain of FGFR2 dramatically increases its affinity
      for keratinocyte growth factor (KGF/FGF-7). We have identified an alternatively
      spliced form of the FGFR3 mRNA, corresponding to known splice variants of FGFRs 1
      and 2. We demonstrate both by binding studies on genetically engineered soluble
      receptors and by the mitogenic response of growth factor-dependent cell lines
      that this splice variant of FGFR3 (FGFR3 IIIb), by binding only acidic FGF
      (aFGF/FGF-1), has the most restricted ligand binding properties of any FGFR thus
      far described. Furthermore, by constructing a chimeric receptor that contains the
      homologous exon from FGFR2, we demonstrate that this single domain from FGFR2 is
      sufficient to confer upon FGFR3 the ability to bind KGF/FGF-7. The uniquely
      limited repertoire of ligands that interact with this receptor suggests that a
      novel ligand for FGFR3 IIIb exists.

PMID- 7512570
TI  - Angiotensin II inhibits cytokine-stimulated inducible nitric oxide synthase
      expression in vascular smooth muscle cells.
AB  - In cultured vascular smooth muscle cells (VSMC), inflammatory cytokines such as
      interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha stimulated nitric
      oxide (NO) production via the expression of an inducible type of NO synthase
      (iNOS). A potent vasoconstrictor, angiotensin II (Ang II), which causes a rapid
      phospholipase C-mediated phosphoinositide hydrolysis via the Ang II type 1 (AT1)
      receptor in VSMC, by itself did not stimulate the production of nitrite, a stable
      metabolite of NO, but dose dependently inhibited the IL-1 beta-induced nitrite
      production. This inhibitory effect of Ang II was blocked by an AT1 receptor
      antagonist, CV-11974, but not by an Ang II type 2 receptor antagonist, PD 123319.
      The presence of Ang II during the early induction phase of iNOS was required for
      this inhibition. Consistently, Ang II suppressed IL-1 beta-induced increases in
      iNOS mRNA and protein levels. Ang II also inhibited increases in nitrite
      production and iNOS mRNA and protein levels caused by tumor necrosis factor
      alpha. A protein kinase C-activating phorbol ester, phorbol 12-myristate 13
      acetate, and a membrane-permeable diacylglycerol, 1,2-dioctanoyl-glycerol,
      similarly inhibited the IL-1 beta-induced nitrite production and iNOS mRNA and
      protein expression, although repetitive additions were needed in the case of
      diacylglycerol. These results indicate that Ang II negatively modulates cytokine
      induced NO production by blocking iNOS expression via the AT1 receptor in VSMC
      and suggest that protein kinase C could be involved in this process.

PMID- 7512571
TI  - Ciliary neurotrophic factor/leukemia inhibitory factor/interleukin 6/oncostatin M
      family of cytokines induces tyrosine phosphorylation of a common set of proteins
      overlapping those induced by other cytokines and growth factors.
AB  - Ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin
      M (OSM), and interleukin-6 (IL6) compose a family of distantly related cytokines
      that initiate signaling by inducing either homodimerization of the "beta" signal
      transducing receptor component gp130 (in the case of IL6) or heterodimerization
      between gp130 and the gp130-related LIFR beta (in the case of CNTF, LIF, and
      OSM); dimerization of beta receptor components in turn activates members of the
      Jak/Tyk family of receptor-associated tyrosine kinases. Here we report that CNTF,
      LIF, OSM, and IL6 induce most of the same protein tyrosine phosphorylations,
      regardless of the cell type assayed or whether they initiate signaling by
      inducing homo- or heterodimerization of beta components. Although several of the
      protein tyrosine phosphorylations induced by the CNTF/LIF/OSM/IL6 family of
      factors may correspond to novel tyrosine kinase targets, we have been able to
      demonstrate the involvement of known signaling molecules, such as phospholipase C
      gamma, phosphoinositol 3-kinase, phosphotyrosine phosphatase (PTP1D), pp120, SHC,
      GRB2, STAT91, Raf-1, and the mitogen-activated protein kinases ERK1 and ERK2,
      revealing substantial convergence not only between the pathways activated by this
      cytokine family and other cytokines, but with pathways previously known to be
      activated only by factors that utilize receptor tyrosine kinases. Our data
      suggest the beta receptor components can form complexes with some of the
      signaling proteins identified and may play some role in their recruitment.

PMID- 7512572
TI  - Recombinant thyroid peroxidase autoantibodies can be used for epitopic
      "fingerprinting" of thyroid peroxidase autoantibodies in the sera of individual
      patients.
AB  - Four human monoclonal antibodies (SP1.4, WR1.7, TR1.8, and TR1.9) map the
      immunodominant region on thyroid peroxidase (TPO) recognized by autoantibodies in
      patients' sera. We used a pool of these monoclonal antibodies, expressed in
      bacteria as antigen-binding fragments [F(ab)], to compete for TPO autoantibody
      binding to radiolabeled TPO. The F(ab) inhibited TPO binding by 32 patients' sera
      by 82 +/- 14% (mean +/- SD), with a range from 51-100%. When each F(ab) was
      tested individually for its ability to compete for autoantibody binding to TPO,
      F(ab) TR1.8 was the most potent among the 32 sera. However, there was a wide
      spectrum of TPO binding inhibition when each serum was considered individually,
      thereby allowing an epitopic "fingerprint" to be drawn for the TPO autoantibodies
      in a patient's serum. There was a close association between the proportions of
      TPO autoantibodies to the TR1.8 and TR1.9 epitopes as well as between those to
      the SP1.4 and WR1.7 epitopes. These associations correspond to the previously
      described A and B epitopic domains in the TPO immunodominant region. No TPO
      epitope was observed to be associated with clinically apparent ophthalmopathy of
      Graves' disease, nor was there an association between TPO epitopes and patient
      age or sex. In summary, the present study on a large sample of sera with TPO
      autoantibodies indicates that by using TPO-specific F(ab) selected to cover all
      regions of the TPO immunodominant region, it is possible to obtain a TPO epitopic
      fingerprint for each serum. These data open the way to future studies directed at
      testing the hypothesis of disease-associated TPO epitope(s).

PMID- 7512574
TI  - Encephalitogenicity of myelin basic protein exon-2 peptide in mice.
AB  - Immunization with a synthetic peptide with an amino acid sequence corresponding
      to mouse myelin basic protein exon-2 induced mild experimental allergic
      encephalitis (EAE) in B10.RIII mice, very mild disease in SJL/J mice and no
      disease in (SJL x PL)F1 hybrid mice. In contrast, adoptive transfer of an exon-2
      peptide-specific T cell line from SJL mice induced severe relapsing EAE in
      syngeneic recipients. The T cell line was specific for exon-2 peptide and did not
      cross-react appreciably with an MBP preparation consisting of the 18.5 and 14-kDa
      isoforms. mRNA for exon-2 containing isoforms could be demonstrated in the spinal
      cord of SJL/J and B10.RIII mice by amplification using exon-2 and exon-4
      oligonucleotide primers. On a relative basis, the level of exon-2 cDNA was lower
      than that of exon-1 cDNA in the same spinal cord preparations from both strains
      of mice.

PMID- 7512573
TI  - Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins
      differently in patients with noninsulin-dependent diabetes mellitus versus
      healthy nonobese and obese subjects.
AB  - In the present study we have 1) assessed how differences in insulin and GH status
      between obese patients with noninsulin-dependent diabetes mellitus (NIDDM) and
      healthy obese (OB) and nonobese (NOB) subjects are associated with different
      responses of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs)
      to fasting, and 2) determined whether the IGF-I response to fasting in healthy
      subjects is secondary to changes in IGFBP-3. In patients with NIDDM, there was a
      lack of response of serum IGF-I concentrations to 4 days of fasting, contrasted
      with the significant decrease in IGF-I concentrations in NOB subjects (37%; P <
      0.001) and the delayed and attenuated decrease in OB subjects (23%; P < 0.01).
      Insulin and the insulin-regulated IGFBP-1 were also unchanged during fasting in
      NIDDM, whereas insulin was decreased and IGFBP-1 was increased in both NOB and OB
      subjects. Insulin-resistant NIDDM patients, with high basal glucose and insulin,
      normal IGFBP-1, and low GH, had decreased prefasting serum IGF-I concentrations,
      similar to the values in fasted body mass index- and age-matched OB subjects.
      IGFBP-3, the major determinant of the IGF-I turnover rate in serum, was unchanged
      by fasting, as determined by RIA and Western ligand blot analysis. In accordance,
      no induction of IGFBP-3 proteolytic activity by fasting could be demonstrated.
      Serum IGF-II concentrations were also unchanged by fasting. Basal immunoreactive
      IGFBP-3 levels did not differ among the groups, whereas IGFBP-3 by Western ligand
      blot analysis was decreased in NIDDM in accordance with the finding of increased
      IGFBP-3 proteolysis in NIDDM. In conclusion, 1) differences in GH status and
      modulation of GH induction of IGF-I by insulin resistance could contribute to low
      basal IGF-I levels and lack of a IGF-I response to fasting in patients with
      NIDDM; and 2) the turnover rate of IGF-I in serum, which is largely determined by
      IGFBP-3, is not likely to be altered by short term fasting, suggesting that the
      decrease in serum IGF-I concentrations is a result of decreased IGF-I production.

PMID- 7512575
TI  - Interleukin-6 secretion from human astrocytoma cells induced by substance P.
AB  - Functional NK-1 (substance P) receptors have been demonstrated previously on
      astrocytes from primary newborn rat brain cultures and human astrocytoma cells
      lines by specific [125I]-Bolton Hunter substance P (SP) binding and by SP-induced
      phosphoinositol turnover. In addition, these cells have been shown to release
      cytokines upon stimulation with interleukin-1 (IL-1) and lipopolysaccharide
      (LPS). Since SP has also been shown to induce cytokine release from rat glial
      cells, this neuropeptide may contribute to the pathophysiology of neuronal
      inflammation in humans by stimulating cytokine production in the brain. We,
      therefore, explored whether SP could induce U-373 MG human astrocytoma cells, via
      specific NK-1 receptor activation, to secrete interleukin-6 (IL-6), a cytokine
      implicated as a key mediator of immune and inflammatory responses. SP stimulated
      IL-6 production in a concentration-dependent manner with an MC50 (concentration
      inducing 50% of the maximum response) of 45 nM. IL-6 was detected in the cell
      culture supernatant fluids 2 h post stimulation and secretion peaked at 12 h. SP
      induced IL-6 secretion was not mediated by IL-1 since neutralizing anti-IL-1
      (alpha and beta) antibody treatment had no effect on the SP response. The
      selective NK-1 receptor agonist, [Sar9, Met(O2)11]-SP, was comparably effective
      to SP in stimulating IL-6 secretion; however, selective NK-2 and NK-3 receptor
      agonists were 250-500-fold less effective. In addition, the non-peptide NK-1
      receptor antagonist, (+/-)CP-96,345, inhibited SP (Ki = 4 nM), but not IL-1
      induced IL-6 release. These selectivity and specificity studies confirmed the
      presence of functional NK-1 type receptors linked to IL-6 release. The results of
      this study support a role for SP as a modulator of immune and/or inflammatory
      processes in the human CNS.

PMID- 7512576
TI  - Differential recognition of sequences within the encephalitogenic region of
      myelin basic protein capable of eliciting cell-mediated immune responses in
      experimental autoimmune encephalomyelitis.

PMID- 7512577
TI  - Somatically mutated member of the human V lambda VIII gene family encodes anti
      myelin-associated glycoprotein (MAG) activity.
AB  - A highly conserved small family of human V lambda genes was identified by DNA
      homology to a V lambda gene isolated from a patient with demyelinating peripheral
      neuropathy, and which encodes an autoantibody with anti-MAG activity. Comparison
      of the genes indicates that the patient V lambda gene was derived from one of the
      germline genes. Together with published analyses of other anti-MAG IgM
      antibodies, which also appear to be mutated in comparison to known germline V
      genes, these results suggest that development of these pathogenic antibodies may
      reflect an antigen-driven, T cell-dependent process.

PMID- 7512578
TI  - Delayed-type hypersensitivity response in experimental autoimmune neuritis
      treated with peptide-coupled spleen cells.
AB  - Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune
      inflammatory disease of the peripheral nervous system that is characterized by
      demyelination and mononuclear cell infiltration. It is induced in Lewis rats by
      administration of myelin P2 protein or a synthetic peptide (SP-26) corresponding
      to amino acid residues 53-78 of bovine P2 protein. Recently, we showed that SP
      26, when coupled to syngeneic spleen cells and administered intravenously,
      provided an effective means of inducing tolerance by inhibiting the clinical
      signs, decreased proliferative response of lymphoid cells to SP-26 and
      histological changes of EAN. However, our current data indicate that, despite
      tolerance induction in these Lewis rats, the antigen-specific delayed-type
      hypersensitivity (DTH) response to SP-26 remained intact. Furthermore, interferon
      (IFN)-gamma production by spleen cells of tolerized rats were unchanged as
      compared to EAN rats. The in vitro proliferation of T lymphocytes from tolerized
      rats stimulated by SP-26 was reduced as compared to EAN controls but was enhanced
      upon addition of exogenous interleukin-2. Thus, reduction in EAN clinical signs
      does not necessarily indicate a decrease in DTH response and IFN-gamma production
      in EAN Lewis rats. The implication of this finding in regard to immunoregulatory
      mechanism of DTH response is discussed.

PMID- 7512579
TI  - Experimental allergic encephalomyelitis induced by the peptide encoded by exon 2
      of the MBP gene, a peptide implicated in remyelination.
AB  - The discovery of T lymphocytes reactive to the peptide encoded by exon 2 of the
      myelin basic protein (MBP) gene in multiple sclerosis (MS) patients has drawn
      attention to MBP isoforms harboring that peptide as candidate autoantigens.
      Previously, immunological studies in MS had almost exclusively used the more
      abundant 18.5 kDa isoform of MBP, which does not contain the exon 2 peptide.
      Investigations of experimental allergic encephalomyelitis (EAE) have also
      focussed on the 18.5 kDa MBP isoform and its peptides. Since EAE is an animal
      model widely used to study MS, we examined the encephalitogenic potential of exon
      2 peptide in the SJL/J mouse. Evidence for increased expression of exon 2
      containing isoforms during remyelination in mouse CNS suggested that exon 2
      sensitized T cells, with encephalitogenic capacity, might be important in the
      perpetuation of relapsing EAE (rEAE). Our experiments have demonstrated that exon
      2 peptide is inherently immunogenic in SJL mice and that EAE could be induced by
      the adoptive transfer of exon 2-sensitized lymphocytes. Furthermore, the disease
      could be accentuated by the transfer of short-term exon 2-reactive lines or by a
      combination of adoptive transfer and antigenic challenge with exon 2 peptide. The
      immunodominant epitope(s) appeared to localize to the segment bordered by amino
      acids 59-85.

PMID- 7512581
TI  - Substance P stabilizes interleukin-2 mRNA in activated Jurkat cells.
AB  - We investigated here the mechanism leading to the enhancement of interleukin (IL)
      2 mRNA that we described in a previous work when Jurkat cells were co-stimulated
      with PHA+PMA and 10(-12) M of the Substance P (SP) neuropeptide. We show that the
      SP-augmented IL-2 mRNA signal is totally abrogated by an early addition of
      cyclosporin A, actinomycin D or cycloheximide. SP does not affect the IL-2 gene
      transcription, as evidenced by nuclear run on assays. In contrast, a
      posttranscriptional alteration of the IL-2 mRNA is shown, by demonstrating that
      the degradation rate of IL-2 mRNA following the addition of actinomycin D, at 4
      h, was delayed in the (PHA+PMA)-activated cell cultures containing 10(-12) M of
      SP. Thus, the SP-induced augmentation of secreted IL-2 in activated T cells we
      demonstrated previously must result from an SP increase of the IL-2 mRNA
      stability.

PMID- 7512580
TI  - Transforming growth factor-beta 1 inhibits tumor necrosis factor
      alpha/lymphotoxin production and adoptive transfer of disease by effector cells
      of autoimmune encephalomyelitis.
AB  - We previously reported that the CD4+ suppressor cells (Ts) that regulate recovery
      of Lewis rats from experimental autoimmune encephalomyelitis (EAE) produce
      transforming growth factor-beta (TGF-beta). We also reported that TGF-beta
      downregulates interferon-gamma (IFN-gamma), but not interleukin-2 (IL-2)
      production, by the CD4+ effector T cells (Te) that mediate EAE. We now report
      that TGF-beta also inhibits the production of tumor necrosis factor/lymphotoxin
      (TNF/LT) by EAE effector cells. When activated in vitro with myelin basic protein
      (MBP), Te produced TNF/LT, as measured using a WEHI 164 cytotoxicity assay. The
      specificity of cytokine action was demonstrated using neutralizing antibodies to
      TNF/LT. When added to the Te+MBP cultures, TGF-beta inhibited TNF/LT production
      in a dose-dependent fashion. Moreover, neutralizing anti-TGF-beta antibodies
      augmented TNF/LT production in the Te+MBP cultures. We also confirm that TGF-beta
      inhibits adoptive transfer of EAE. In contrast, murine IL-10 only partially
      inhibited TNF/LT and IFN-gamma production by Te. We conclude that TGF-beta
      production by Ts plays a major role in recovery from EAE in the Lewis rat by
      inhibiting TNF/LT and IFN-gamma production by the effector cells that mediate
      EAE.

PMID- 7512582
TI  - Perturbation of epidermal barrier function correlates with initiation of cytokine
      cascade in human skin.
AB  - BACKGROUND: An important function of skin is to serve as a barrier and thus
      provide protection from the external environment. The epidermal keratinocyte
      establishes this barrier by producing an intact stratum corneum. In the past,
      keratinocytes were appreciated only for this rather inert, passive structural
      responsibility and not for their potential dynamic contribution to inflammatory
      or immune-mediated reactions. OBJECTIVE: Our purpose was to examine the cascade
      of molecular and cellular events that occur when the barrier function of human
      skin is abrogated by repeated tape stripping, which physically removes the
      stratum corneum without inducing any cytopathic effects on the underlying
      epidermal keratinocytes. METHODS: Eight healthy human volunteers underwent
      repeated tape stripping and sequential punch biopsy specimens of skin obtained
      between 1 and 24 hours after tape stripping were analyzed for protein antigens by
      immunostaining of cryostat-cut sections. The presence or absence of various
      messenger RNAs (mRNAs) were detected by polymerase chain reaction. RESULTS: After
      repeated tape stripping, keratinocytes became activated within hours. The
      responses included up-regulation of keratin-16 expression and keratinocyte
      proliferation accompanied by production of a specific profile of cytokine and
      adhesion molecule mRNAs and proteins in both epidermal and dermal compartments.
      Polymerase chain reaction amplification of RNA species isolated from the
      epidermal portion of skin revealed increases 6 hours after tape stripping in mRNA
      coding for tumor necrosis factor-alpha, IL-8, IL-10, interferon gamma,
      intercellular adhesion molecule-1, transforming growth factor-alpha, and
      transforming growth factor-beta. There was no increase in tumor necrosis factor
      alpha, IL-8, IL-10, or transforming growth factor-alpha mRNAs in the dermal
      samples. Immunostaining revealed that keratinocyte intercellular adhesion
      molecule-1 was increased 6 hours after stripping and was accompanied by
      endothelial cell expression of E-selectin (endothelial cell adhesion molecule-1)
      and vascular cell adhesion molecule-1. These molecular events, which occurred
      after 6 hours in tape-stripped skin, preceded any movement of inflammatory cells
      from the circulation into dermis or epidermis and hence reflect changes that
      occur in cells indigenous to normal human skin. None of these changes occurred in
      persons who underwent limited tape strippings without barrier perturbation.
      CONCLUSION: The results highlight the rapid and distinctive responses of
      epidermal keratinocytes and demonstrate that these cells can actively participate
      in a far greater number of homeostatic responses other than the production of the
      epidermal barrier.

PMID- 7512583
TI  - Response of psoriasis to a new topical retinoid, AGN 190168.
AB  - BACKGROUND: Oral retinoids have been widely used in psoriasis, but topical forms
      have been ineffective or irritating. OBJECTIVE: Our purpose was to determine the
      clinical and molecular effects of a new topical retinoid, AGN 190168, on
      psoriasis. METHODS: Seven patients with psoriasis were treated for 2 weeks with
      topical retinoid and 2 weeks with vehicle. Two control subjects with psoriasis
      were treated for 2 weeks with vehicle alone. Biopsy specimens from normal skin as
      well as from untreated and treated psoriatic lesions were compared by
      immunohistochemical analysis. Differentiation and inflammatory markers were
      studied. RESULTS: Clinical improvement was seen in all seven patients after 2
      weeks of treatment. Improvement was still present, but not significant, after 2
      additional weeks of vehicle application. Histologic examination showed a return
      to a more normal morphology in four of seven biopsy specimens, which correlated
      with filaggrin expression. There was a diminution in the precocious expression of
      keratinocyte transglutaminase, keratin 16, and involucrin, as well as a decrease
      in epidermal growth factor receptor and in the number of cells expressing
      intercellular adhesion molecule type 1 and HLA-DR. CONCLUSION: Clinical and
      histologic improvements were seen in psoriasis in association with the topical
      application of AGN 190168 at 2 weeks, including decreased inflammation and
      restoration of normal epidermal differentiation. Small patient numbers and the
      possibility that the changes were related to clinical improvement alone and not
      the topical agent preclude definitive conclusions.

PMID- 7512584
TI  - NADPH-diaphorase activity of nitric oxide synthase in the olfactory bulb: co
      factor specificity and characterization regarding the interrelation to NO
      formation.
AB  - The neuronal form of the enzyme nitric oxide synthase (nNOS) synthesizes the
      messenger molecule nitric oxide (NO). In addition to NO formation, nNOS exhibits
      a so-called NADPH-diaphorase (NADPH-d) activity. This study focused on the
      characterization of NADPH-d activity with regard to NO formation in the rat
      olfactory bulb. In this area of the brain pronounced staining is localized in
      discrete populations of neuronal somata and in olfactory glomeruli. Diaphorase
      staining combined with demonstration of nNOS by polyclonal antibodies revealed
      that NADPH-d activity of neuron somata is associated with nNOS immunoreactivity.
      It is concluded that neuron somata exhibit NADPH-d activity of nNOS. NADPH-d
      activity of nNOS did not utilize beta-NADH or alpha-NADPH. Moreover, NADPH-d
      activity was inhibited in the presence of alpha-NADPH. Dichlorophenolindophenol
      (DPIP), an artificial electron acceptor and an inhibitor of NO formation, totally
      suppressed NADPH-d staining of neurons, supporting the concept that the NADPH-d
      of neuron somata is due to nNOS. Cytochrome C, miconazole, EGTA, and
      trifluoperazine, which have been reported to inhibit cytochrome P450 reductase
      activity of NOS, did not affect NADPH-d staining. Hence, NADPH-d activity of NOS
      does not involve cytochrome P450 reductase activity as required for NO formation.
      Contrary to NADPH-d activity of neuron somata, staining of olfactory glomeruli
      was not co-localized with nNOS immunoreactivity. Glomerular staining was also
      observed in the presence of beta-NADH and alpha-NADPH. Further, it was unchanged
      in the presence of the NO formation inhibitor DPIP. Hence, the glomerular
      staining in the presence of NADPH is not due to the NADPH-d activity of NOS. We
      conclude that staining of neuronal structures in the presence of NADPH does not
      necessarily represent NADPH-d activity of NOS.

PMID- 7512586
TI  - Immunostaining of DNA in electron microscopy: an amplification and staining
      procedure for thin sections as alternative to gold labeling.
AB  - We describe a new electron microscopic on-section staining technique with high
      specificity and sensitivity for DNA-containing structures. Lowicryl HM20 sections
      of specimens obtained by cryofixation and freeze-substitution are incubated in a
      first step with a primary IgM antibody specific for double-stranded DNA. The
      layer of bound antibodies at the section surface is amplified in a successive
      step by a secondary IgG antibody. Finally, electron scattering of the antibody
      layer produced is enhanced by staining with a mixture of uranyl acetate and
      potassium permanganate. The applicability of the method is exemplified by the
      detection of shape and distribution of various types of bacterial and eukaryotic
      chromatin.

PMID- 7512585
TI  - Generation of a murine monoclonal antibody to normal mammary epithelium using
      mice rendered immune-tolerant to malignant mammary epithelium.
AB  - A monoclonal antibody (MAb) that distinguishes normal from malignant mammary
      epithelia in tissue or cell lines was generated using a procedure that involved
      immune-tolerization before immunization. Immune-tolerance to two transformed
      mammary epithelial cell lines (MCF.7 and MDA.MB.231 cell lines combined) was
      induced in neonatal mice within 24 hr of birth. Successful induction of immune
      tolerance was determined by an indirect immunohistological method, testing sera
      from mice against the tolerogen (i.e., the MCF.7 and MDA.MB.231 cell lines). Mice
      lacking antibodies in their sera against the immune-tolerogen were subsequently
      immunized with an extract of normal breast epithelium. One mouse was selected for
      hybridoma production based on evidence of serum antibody that showed reactivity
      with normal mammary epithelial cells (MEC) but not with invasive breast carcinoma
      cells, as determined by an indirect immunohistological method. Spleen cells from
      the selected mouse were fused with a mouse myeloma cell line to generate MAb.
      After extensive screening, one MAb was further studied on the basis of reactivity
      with normal MEC in tissue and absence of staining of malignant MEC in tissue or
      tumorigenic MEC lines. This test of specificity of reactivity revealed that the
      antigen detected by the specific antibody was expressed on the apical plasma
      membrane of normal glandular epithelia that included breast, cervix, colon, lung,
      pancreas, and stomach, but not on their malignant counterparts in tissue
      sections. The antigen recognized by the MAb was termed luminal epithelial antigen
      with an apparent MW of 92 KD (LEA.92). This study illustrates the practical
      usefulness of the immune-tolerization/immunization approach in the generation of
      antibodies with particular specificity requirements, as in the identification of
      an antigen that is differentially expressed in two tissues (e.g., normal and
      malignant) which otherwise have a multiplicity of antigens in common.

PMID- 7512587
TI  - Expression of Forssman antigen in human large intestine.
AB  - Forssman antigen is a commonly occurring heterophile antigen but is thought not
      to be present in most humans. Recent biochemical studies, however, have shown the
      presence of Forssman antigen in several forms of human cancer, including gastric,
      colon, and lung cancers. Immunohistochemical staining with both monoclonal and
      polyclonal antibodies has failed to demonstrate this antigen in human tissues. In
      this study we conclusively demonstrated the presence of Forssman antigen in
      cytoplasm of colon goblet cells, especially those in the so-called transitional
      mucosa adjacent to carcinoma. Specimens from 69 of 70 patients with colon cancer
      contained the antigen in goblet cells in transitional mucosae. The antigen was
      successfully demonstrated only after removal of sialic acid by alkaline
      hydrolysis-neuraminidase digestion. Localization of the antigen was quite
      different from that of Tn and human blood group A, B, and H antigens. This
      antigen was thought to be associated exclusively with globo-series glycolipids,
      and its existence in glycoproteins has not been conclusively demonstrated.
      However, the results presented here, based on proteolytic digestion and lipid
      extraction studies, strongly suggest that the antigen is also contained in
      glycoproteins.

PMID- 7512588
TI  - Giemsa as a fluorescent stain for mineralized bone.
AB  - We present evidence for a previously unrecognized differential staining effect of
      Giemsa solution in fluorescence microscopy. The effect consists of selective
      fluorescent staining of mineralized bone (and elastic fibers) in tissue sections
      and, like the classical Romanowsky effect, is based on the differential binding
      of Eosin Y to tissue structures in the presence of Azur II and Methylene Blue.
      This effect opens the way to new applications of the Giemsa solution in
      fluorescence microscopy and in confocal fluorescence microscopy.

PMID- 7512589
TI  - How many specific B cells are needed to protect against a virus?
AB  - The size of the Ab repertoire has been estimated to comprise theoretically
      somewhere between > 10(10) and approximately 10(4) specificities, dependent on
      the criteria used. In an attempt to estimate the anti-viral protective Ab
      repertoire of the mouse the B cell and Ab-forming cell (AFC) frequencies and
      protective neutralizing Ab levels during the course of an infection with
      vesicular stomatitis virus (VSV) were analyzed. Determination of AFC frequencies,
      limiting dilution assays, and adoptive transfer experiments to SCID mice revealed
      that during the acute phase (day 8) of the immune response, more than 50% of all
      IgG2a-producing AFCs were specific for VSV, most of them recognizing the
      neutralizing determinant. In a later phase (days 21 or 50), 10 to 20 times fewer
      VSV-specific AFCs were present, corresponding to a frequency of approximately
      1:10(4) spleen cells. Finally, in a protection assay in SCID mice, adoptively
      transferred protective Ab concentrations were found to be approximately 1 to 10
      micrograms Ab/ml mouse serum. Because during the memory phase of the anti-VSV
      response usually 10(4) AFC/mouse are engaged to maintain a high level of memory
      IgG against the neutralizing determinant on VSV and if one assumes a total number
      of about 10(6) AFCs/mouse, these data suggest a rather limited neutralizing anti
      viral protective memory-AFC repertoire of 10(2) to 10(4) different specificities.

PMID- 7512590
TI  - Regulatory effects of prostaglandin E2 on the growth and differentiation of human
      B lymphocytes activated through their CD40 antigen.
AB  - We have studied the effects of prostaglandin E2 (PGE2) on the growth and
      differentiation of human tonsillar B lymphocytes cultured in the CD40 system with
      or without IL-4 or IL-10. PGE2 (10(-9) to 10(-6) M) enhanced proliferation of B
      cells activated through their CD40 Ag, but not their Ig secretion. PGE2 further
      potentiated both IL-4- and IL-10-induced B cell growth as determined by [3H]TdR
      uptake and cellular enumeration. The IL-10-induced IgM, IgG, and IgA secretion
      was enhanced twofold to fourfold after addition of PGE2, whereas IL-4-induced IgG
      and IgE secretion was inhibited. The IgE production was particularly sensitive as
      an approximately 90% inhibition was obtained for 10(-7) M PGE2. In addition, PGE2
      inhibited IgE production by naive surface IgD+ B cells cultured in the CD40
      system, suggesting that PGE2 may interact with mechanisms involved in IgE
      switching. PGE2 displayed similar effects on cytokine-induced proliferation and
      Ig secretion of B cells activated by anti-CD40 Abs used in a soluble form.
      Finally, the PGE2 effects were mimicked by agents increasing cAMP, indicating
      that the PGE2 activities are likely to depend on the activation of the cAMP
      pathway. Altogether, the present data indicate that PGE2 stimulates human CD40
      activated B cell growth, but differently modulates cytokine-induced
      differentiation. Thus, in microenvironments supporting the development of an
      immune response, the secretion of PGE2 by competent cells such as macrophages may
      participate in the regulation of the humoral response.

PMID- 7512592
TI  - Immunological mimicry between N-acetyl-beta-D-glucosamine and cytokeratin
      peptides. Evidence for a microbially driven anti-keratin antibody response.
AB  - We discovered recently that a subset of mouse anti-streptococcal mAbs cross
      reacted with N-acetyl-beta-D-glucosamine (GlcNAc) and certain cytoskeletal
      proteins, and recognized both carbohydrate and peptide antigenic determinants. To
      further study the nature and biologic significance of immunologic mimicry between
      carbohydrate and peptide Ags, eight human hybridomas secreting anti-GlcNAc mAbs
      were produced by in vitro stimulation of PBL with streptococcal peptidoglycan
      polysaccharide complexes and pokeweed mitogen. All human anti-GlcNAc mAbs
      described in this study were shown to express marked cross-reactivity with
      keratin from human skin in the ELISA and Western immunoblot. Mapping of the mAbs
      with overlapping synthetic decapeptides of the entire amino acid sequence of
      human cytokeratin 14 revealed that human anti-GlcNAc mAbs recognized specific
      cytokeratin decapeptides. Four human anti-GlcNAc mAbs recognized a single
      cytokeratin decapeptide whereas two mAbs reacted with several individual peptide
      epitopes in different fragments of cytokeratin 14. In addition, two mAbs, 1.C8
      and 9.B12, reacted with multiple cytokeratin decapeptides, predominantly in the
      head domain of the molecule, and their reactivity correlated with positive
      binding of the mAbs to cytokeratin 14 in the Western immunoblot and with positive
      staining of human epidermis in the indirect immunofluorescent assay. Finally, we
      demonstrated that Abs to keratin and synthetic keratin decapeptides were induced
      in BALB/c mice immunized with GlcNAc-BSA but not with BSA, suggesting that the
      anti-keratin Ab response in vivo may be driven by nonkeratin Ags containing
      terminal O-linked GlcNAc.

PMID- 7512591
TI  - B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10.
AB  - We analyzed the effects of rIL-10 on IL-5 production by human resting T cells
      isolated from peripheral blood. Resting T cells of healthy individuals required
      activation for 48 h with either anti-CD3 mAb cross-linked on B7/CD32-transfected
      mouse fibroblasts or PMA in conjunction with anti-CD28 mAb for optimal IL-5
      secretion. In each condition, IL-5 secretion measured by ELISA was inhibited in a
      dose-dependent manner by rIL-10, whereas IFN-gamma production was not suppressed.
      The inhibitory effect of rIL-10 on IL-5 synthesis induced by PMA and anti-CD28
      mAb was also observed at the mRNA level. In contrast with its action on T cells
      costimulated by B7/CD28 signaling, rIL-10 did not block IL-5 secretion in
      response to PMA and A23187 calcium ionophore. The inhibition of IL-5 production
      by rIL-10 was not due to IL-2 deprivation because it was not modified by the
      addition of exogenous rIL-2. Moreover, cyclosporin A, which inhibited IL-2 more
      efficiently than rIL-10 in response to anti-CD3 mAb and B7/CD32 transfected
      fibroblasts, did not reduce and even enhanced IL-5 production. Finally, we
      analyzed the influence of endogenously produced IL-10 on IL-5 secretion by T
      cells stimulated by PMA and anti-CD28 mAb. Addition of a neutralizing anti-IL-10
      mAb increased IL-5 release in this system, indicating that endogenous IL-10
      controls IL-5 production. We conclude that both rIL-10 and endogenous IL-10
      inhibit IL-5 production by T cells costimulated by B7/CD28 signaling.

PMID- 7512593
TI  - Antigen presentation is enhanced by targeting antigen to the Fc epsilon RII by
      antigen-anti-Fc epsilon RII conjugates.
AB  - Targeting Ag to the Fc epsilon RII by Ag-specific IgE has been shown to be an
      efficient means of enhancing Ag presentation by B cells to Ag-specific T cells.
      To take advantage of the Fc epsilon RII as a targeting molecule and to
      investigate whether IgE was required for mediation of the enhanced stimulation,
      Ag was covalently coupled to anti-Fc epsilon RII by using heterobifunctional
      crosslinking reagents. These Ag-Ab conjugates were used with T cell lines
      specific for the Ags, OVA (BB6.5) or rabbit gamma-globulin (CDC35 and D1.6), and
      splenic B cells to examine both B cell and T cell proliferation in vitro.
      Significant presentation of Ag-anti-Fc epsilon RII conjugates was apparent at
      doses of Ag 1,000- to 10,000-fold lower than seen with unconjugated Ag alone. Ag
      presentation with the use of anti-Fc epsilon RII-Ag conjugates was as good as or
      better than conjugates with Ab to the adhesion molecule Pgp-1 or control Ab in T
      cell proliferation and better than those conjugates in B cell proliferation
      assays (10- to 100-fold). Anti-Fc epsilon RII-Ag conjugates were clearly more
      effectively presented than Ag-anti-Fc gamma RII conjugates (> 100-fold). Mouse Fc
      epsilon RII is presently known to be expressed on B cells and follicular
      dendritic cells and these in vitro results suggest that the conjugates would be
      useful tools for investigating the role of IgE-mediated B cell Ag presentation in
      vivo. BALB/c mice immunized with OVA-anti-Fc epsilon RII conjugates made a quite
      significant OVA-specific IgG1 response and a detectable IgE response. No
      detectable Ab was produced in response to OVA alone and a minimal response was
      seen when an isotype-matched control conjugate was used. Thus, the results
      indicate that Fc epsilon RII targeting is operative both in vivo and in vitro.

PMID- 7512594
TI  - Efficient induction of immunoglobulin production in neonatal naive B cells by
      memory CD4+ T cell subset expressing homing receptor L-selectin.
AB  - The humoral response in newborns is mainly restricted to IgM production, which
      may be attributable to the naive nature of both B and T cells at birth. In light
      of the current evidence that memory (CD45RO+) CD4+ T cells help B cell
      differentiation, the present study was undertaken to examine whether a specified
      population within memory CD4+ T cells could induce the maturation of neonatal
      naive B cells. In the conventional PWM-stimulated cultures, the generation of IgG
      and IgA-producing cells in addition to IgM production by neonatal B cells was
      significantly enhanced by co-cultures with memory, but not naive, CD4+ T cells.
      Memory CD4+ T cells were further divided into two populations based on expression
      of homing receptor L-selectin. These memory CD4+ T cell subpopulations appeared
      to behave in different fashions concerning help for Ig production by naive
      (sIgD+) and mature (sIgD-) B cells. L-selectin-negative memory CD4+ T cells
      exhibited helper function for Ig secretion by mature B cells. Intriguingly, Ig
      production by neonatal B cells as well as adult naive B cells, although less than
      that by mature B cells, was efficiently promoted by L-selectin-positive memory
      CD4+ T cells rather than L-selectin-negative ones. The results suggest that the
      capability of neonatal naive B cells to secrete IgG and IgA can be elicited by
      appropriate T-cell signals, especially from the L-selectin-positive population
      within memory CD4+ T cells, seemingly indicating its possible role for isotype
      switching in B cells.

PMID- 7512595
TI  - Simultaneous regulation of CD2 adhesion and signaling functions by a novel CD2
      monoclonal antibody.
AB  - Accessory molecules on T cells can support adhesion and transduce agonistic
      signals that facilitate Ag receptor-induced T cell activation. The T cell
      differentiation Ag CD2 may exert both functions, as has been amply demonstrated
      in studies with CD2 mAbs. In addition, experiments in which either purified
      ligand (CD58) or transfected CD2 and CD58 molecules were used have confirmed this
      notion. However, controversy exists as to whether CD2 alters its affinity for
      CD58 in the course of T cell stimulation, and whether this putative affinity
      change affects CD2-mediated activation signals. We now describe a CD2 mAb (HIK27)
      that recognizes an epitope constitutively expressed on resting T cells and
      induces increased adhesiveness of CD2 toward CD58. Addition of HIK27 to a
      stimulatory but nonmitogenic pair of CD2 mAbs induces a strong proliferative
      response. Finally, HIK27 was found to be co-mitogenic with CD58 expressed on
      sheep erythrocytes, B cell lines, and CD58-transfected L cells. The simultaneous
      modulation of CD2 adhesion and signaling on HIK27 binding suggests that both
      functions of the molecule may be enhanced in the course of T cell stimulation.

PMID- 7512596
TI  - Membrane-proximal Ig-like domain of Fc gamma RIII (CD16) contains residues
      critical for ligand binding.
AB  - Ag-Ab complexes are cleared from the circulation through a complex system of
      receptors for the Fc portion of Ig (FcRs). Fc gamma RIII (CD16) is a low affinity
      FcR for IgG that is composed of two highly homologous Ig-like extracellular
      domains. Using secondary structure predictions, we located a strongly hydrophilic
      region in the second Ig-like domain of Fc gamma RIII that is predicted to lie
      between beta-strands C and C'. Substitutions of seven out of eight amino acids in
      this region abolished binding to IgG. Substitution of a conformationally adjacent
      amino acid in a bend just before beta-strand F and an amino acid in the B-C loop
      also affected ligand binding. However, amino acid substitutions in two different
      predicted loops in the second Ig-like domain as well as substitutions to three
      predicted loops in the first Ig-like domain had no effect on function. A chimeric
      Fc gamma RIII molecule lacking the second Ig-like domain was unable to bind IgG
      further, suggesting the presence of the binding site in the second domain.
      Neutralizing mAbs that inhibit Fc gamma RIII interaction with IgG were mapped to
      the E-F loop in the membrane proximal domain of Fc gamma RIII, providing further
      evidence of the importance of this region of the molecule in ligand interaction.

PMID- 7512597
TI  - HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same
      face of CD4.
AB  - Although the HIV gp120 binding site of CD4 is well characterized, its interaction
      site with HLA class II molecules is still controversial. Sixty-seven mutations
      within the four extracellular domains of CD4 were examined for their effects on
      cell surface expression and conformational changes and for adhesion of HLA class
      II-expressing B lymphocytes and HIV gp120 binding to CD4-transfected COS cells.
      Mutations within the gp120 binding site affected both assays similarly,
      indicating that the two sites fully overlap. A few additional substitutions of
      residues mapping on the same face of domains 1 and 2 induced decreased rosette
      formation. Molecular modeling studies indicated that this is likely to be the
      consequence of conformational changes induced by the mutations. Thus, CD4 appears
      to interact with HLA class II molecules mainly through the HIV gp120 binding site
      and possibly through a second minor interaction site mapping on the same face of
      the molecule.

PMID- 7512598
TI  - Definition of a DQ3.1-specific binding motif.
AB  - A quantitative peptide binding assay using purified DQA1*0301/DQB1*0301 (DQ3.1)
      molecules was developed and validated by examining the correlation between the
      data obtained in the binding assay with those obtained in inhibition of Ag
      presentation assays. By the combined use of large libraries of synthetic peptides
      and of substitution and truncation analogues, a putative DQ3.1 motif was defined.
      Its most prominent feature is the requirement for two small and/or hydrophobic
      residues spaced at positions i + 2 and i + 4. This motif is quite different from
      the motif recognized by DR molecules, but similar to the motif previously defined
      for certain IA alleles (the putative mouse homologue of DQ). These data suggest
      that various class II isotypes have evolved to present different peptide
      structures to each other, thus maximizing the repertoire of different epitopes
      available to T cell scrutiny.

PMID- 7512599
TI  - Vitronectin, fibronectin, and gp120 antibody enhance macrophage release of TNF
      alpha in response to Pneumocystis carinii.
AB  - Alveolar macrophages (AMS) initiate inflammation during Pneumocystis carinii
      pneumonia by releasing cytokines including TNF-alpha. Recent studies suggest that
      macrophage responses to P. carinii are enhanced by serum opsonization, but the
      mechanisms of enhancement are not well defined. To determine whether macrophage
      release of TNF-alpha in response to P. carinii was augmented by immune
      opsonization, alveolar macrophages obtained from rabbits were cultured with P.
      carinii that had been opsonized with either nonimmune rabbit serum, immune serum
      generated against P. carinii, or an affinity-purified polyclonal Ab recognizing
      the major P. carinii surface Ag gp120. Each experiment also included organisms
      maintained in media alone (nonopsonized P. carinii). Opsonization of P. carinii
      with immune serum or gp120 Ab significantly enhanced macrophage TNF-alpha
      release. Interestingly, however, opsonization with nonimmune serum also increased
      TNF-alpha response to the organism. Because P. carinii is known to interact with
      the adhesive glycoproteins, vitronectin (VN) and fibronectin (FN), we
      hypothesized that they might also augment TNF-alpha release. Opsonization of P.
      carinii with VN or FN resulted in significant potentiation of macrophage TNF
      alpha liberation. We further determined that VN and FN were present in increased
      quantities in the lower respiratory tract of patients with P. carinii pneumonia
      compared with normal volunteers. Additionally, VN and FN were demonstrated on the
      surface of freshly isolated P. carinii organisms by immunoblot analysis. Our
      study suggests that immune and nonimmune opsonins contribute to host defenses
      during P. carinii pneumonia by enhancing regional TNF-alpha release in response
      to the organism.

PMID- 7512600
TI  - The leukocyte integrin p150,95 (CD11c/CD18) as a receptor for iC3b. Activation by
      a heterologous beta subunit and localization of a ligand recognition site to the
      I domain.
AB  - p150,95 is a member of the leukocyte integrin family of adhesion proteins.
      Compared with LFA-1 and Mac-1, p150,95 is less well functionally characterized.
      Although p150,95 has complement receptor activity for iC3b and has been
      designated complement receptor type 4, transfected cells expressing p150,95 do
      not bind iC3b-sensitized cells. We report that cells cotransfected with a human
      p150,95 alpha subunit and a chicken, but not human, beta subunit bind IgM-iC3b
      coated erythrocytes, suggesting that interactions between the alpha and beta
      subunits can regulate p150,95 adhesiveness. Furthermore, purified human p150,95
      binds to cell-bound iC3b-coated erythrocytes. Because binding to iC3b by cellular
      and purified p150,95 is specifically abolished by mAbs that localize to the I
      domain of p150,95, we suggest that the I domain of the p150,95 alpha subunit is
      an important ligand recognition site for iC3b.

PMID- 7512601
TI  - Induction of vascular addressins and adhesion molecules in the pancreas of IFN
      gamma transgenic mice.
AB  - "Vascular addressins" play an important role in lymphocyte homing to chronic
      inflammatory areas. However, it is not yet known which cytokines induce vascular
      addressins and other adhesion molecules in vivo. Because IFN-gamma induces
      adhesion molecules in vitro, we tested the ability of IFN-gamma to induce
      vascular addressins and other adhesion molecules in vivo employing a transgenic
      mice model that expresses IFN-gamma in pancreatic beta-cells and develops
      insulitis (Ins-IFN-gamma mice). Two vascular addressins were induced in the
      transgenic pancreata. The first was MadCAM-1, a mucosal vascular addressin
      recognized by MECA-367 and required for lymphocyte homing to Peyer's patches. The
      second was a peripheral lymph node vascular addressin recognized by MECA-79 and
      required for homing to peripheral nodes. ICAM-1 was expressed on ductal
      epithelial cells, endothelial cells, and the majority of infiltrating lymphocytes
      as well as its ligand LFA-1. Lymphocyte-deficient transgenic mice were also
      induced to express vascular addressins and ICAM-1, suggesting that probably IFN
      gamma itself stimulated the expression of those molecules, not cytokines secreted
      from infiltrating lymphocytes. LPAM and L-selectin, potential counter-receptors
      for vascular addressins, were expressed on infiltrating lymphocytes. These
      results underscore the importance of IFN-gamma as an inducer of vascular
      addressins in vivo.

PMID- 7512602
TI  - Acquired C1 inhibitor deficiency as a result of an autoantibody to the reactive
      center region of C1 inhibitor.
AB  - An autoantibody that we hypothesize to react with the reactive center of the
      plasma serine proteinase inhibitor, C1 inhibitor (C1INH), has been found in a
      patient with acquired C1INH deficiency. The Ab blocks the ability of C1INH to
      inhibit the hydrolysis of N-carbobenzyloxy-L-lysine thiobenzylester by purified
      C1s. A cryoprecipitate from the patient's plasma as well as the Ig fraction were
      able to block C1INH inhibition of C1s. The immunoaffinity purified Ab to C1INH
      from the patient's plasma Ig fraction neutralizes the inhibitory activity of
      C1INH in a dose-dependent manner and blocks the ability of normal C1INH to form a
      complex with C1s. The neutralizing activity of the purified Ab is reversed by a
      synthetic peptide that corresponds to the amino acid sequence in the P1 to P15
      positions of the reactive center of C1INH but not by a 34-amino-acid trypsin
      peptide or 37-amino-acid elastase peptide derived from the C-terminus of C1INH.
      Western blot analysis indicated that the Ab is an oligoclonal Ig with kappa light
      chains.

PMID- 7512603
TI  - Recognition of T cell epitopes and lymphokine secretion by rye grass allergen
      Lolium perenne I-specific human T cell clones.
AB  - T cell lines (TCL) and CD4+ T cell clones (TCC) with specificity for the rye
      grass allergen Lolium perenne (Lol p) I were isolated from the blood of nine
      donors, six having active atopic disease, two being in remission, and one having
      IgE anti-Lol pI Abs but not atopic disease. The T cell epitopes of Lol pI were
      determined by TCLs and TCCs reactivity with 23 overlapping, 20 amino acid-long
      peptides spanning the entire length of the 230 amino acid-long allergen. In
      addition, the Th subsets (Th1, Th2, Th0, Thp) were determined by measuring IL-2,
      IFN-gamma, and IL-4 in the supernatants of TCC activated with Lol pI and
      irradiated APC. TCC from individuals from which a large panel of clones were
      obtained from 10(5) PBMC initial cultures recognized multiple peptides (5-9) and
      23 overlapping peptides a total of 16 were recognized by at least one TCC from
      one of the patients. These 16 peptides were derived from all areas of the Lol pI
      molecule, indicating the ability of human Th cells to recognize many peptide
      epitopes on Lol pI. Although no clear cut immunodominant peptides were detected,
      T cell clones of 50% of the patients reacted with peptide 191-210. There was no
      correlation between peptide epitope reactivity and lymphokine secretion pattern
      of the TCC. Of 12 TCC obtained from six patients with active atopic disease, four
      (33%) were of Th1, five (42%) of Th2, one (8%) of Thp, and two (17%) of Th0 type.
      Of 14 TCCs isolated from three atopic donors in remission, five (36%) were of
      Th1, three (21%) of Th2, four (29%) of Thp, and two (14%) of Th0 type. The data
      demonstrate that T cells from rye grass pollen allergic patients can recognize
      multiple peptide epitopes on Lol pI scattered over the entire molecule. No
      correlation existed between epitope reactivity and lymphokine secretion pattern
      of the TCC.

PMID- 7512604
TI  - Target organ-specific up-regulation of the MRC OX-40 marker and selective
      production of Th1 lymphokine mRNA by encephalitogenic T helper cells isolated
      from the spinal cord of rats with experimental autoimmune encephalomyelitis.
AB  - Lewis x Buffalo F1 rat lymphocytes express both forms of the allelic marker RT7.1
      (Lewis) and RT7.2 (Buffalo). We generated myelin basic protein (MBP)-specific
      encephalitogenic F1 T helper cell lines and adoptively transferred them into
      naive irradiated Lewis recipients, which enabled us to detect and isolate donor T
      cells (with RT7.2) within the recipients. The spinal cord and cerebrospinal fluid
      (CSF) were highly enriched for the donor T cells compared with the blood and
      spleen. The donor cell number peaked on the first day of disease in the spinal
      cord and CSF and decreased as the disease progressed. A high percentage of the
      donor T cells isolated from the spinal cord were positive for the T helper cell
      activation marker OX-40, whereas a (lower) percentage of CSF donor cells
      expressed OX-40. Donor cells isolated from blood or spleen were negative for OX
      40 expression. In contrast, the IL-2 receptor (CD25) was positive on all the
      transferred T cells in all tissue sites examined. Cell-sorting experiments showed
      that the MBP-specific donor cells were enriched for IFN-gamma, IL-2, TNF-alpha,
      and IL-3 mRNA when compared with the host-recruited spinal cord cells, whereas
      similar amounts of IL-10 mRNA were produced by both populations. Lymphokine mRNA
      production was also enriched in donor T cells isolated from the spinal cord
      compared with donor T cells isolated from the spleen. The spinal cord donor cells
      produced higher levels of IL-2, IFN-gamma, and IL-3 mRNA, whereas similar amounts
      of IL-10 and TNF-alpha mRNA were produced from donor cells isolated from the
      spleen and the spinal cord. Our data suggest that the amount/percentage,
      activation state, and enhanced lymphokine production at the site of inflammation
      are all important factors in determining the autoimmune potential of Ag-specific
      effector T helper cells.

PMID- 7512607
TI  - Solid-phase antigen density and avidity of antibodies detected in anti-group B
      streptococcal type III IgG enzyme immunoassays.
AB  - Two enzyme immunoassays which measure anti-group B streptococcal type III
      capsular carbohydrate IgG antibodies were compared. One utilised poly-L-lysine
      conjugated coating antigen while the other used tyraminated coating antigen. Both
      carbohydrate antigens appeared to be antigenically identical but the poly-L
      lysine based assay gave significantly lower values for some sera. Sera were
      identified which had low and high avidity anti-group B streptococcal type III IgG
      antibodies by the thiocyanate elution method. These antibodies gave results on a
      dilution range of coating concentrations consistent with their relative avidity.
      Comparison of dilution ranges of the two conjugates used for coating suggests
      that the poly-L-lysine conjugate coats with a ten-fold lower efficiency than the
      tyramine conjugate and therefore detects only higher avidity antibodies. Four
      fractions containing different relative avidities of affinity-purified IgG were
      produced from a single serum. These fractions behaved in the same manner as sera
      containing antibodies of different avidities. The results of this study suggest
      that the method of polysaccharide conjugation in enzyme immunoassays may affect
      the antigen concentration on the solid phase and thence the detection of
      antibodies of various avidities.

PMID- 7512605
TI  - Spectroscopic evidence that monoclonal antibodies recognize the dominant
      conformation of medium-sized synthetic peptides.
AB  - Spectroscopic methods have amply documented that small- and medium-sized peptides
      tend to assume unordered conformations in water. The conformational tendencies,
      however, manifest in halogenated alcohols, and the preferred secondary structures
      are apparent from the circular dichroism (CD) spectra. Here we report the results
      of immobilizing peptide and protein antigens from various mixtures of
      trifluoroethanol and water during enzyme-linked immunosorbent assays. The
      increased recognition by the appropriate monoclonal antibodies (mAbs) is
      correlated with the increase of the alpha helical, beta turn, or beta pleated
      sheet content of the peptides presented in the different solvent mixtures.
      Remarkably, the antibody binding can be detected at considerably lower antigen
      levels if the antigen is immobilized from trifluoroethanol. The antigens we used
      corresponded to fragments of normal human neurofilaments and tau protein found in
      the paired helical filaments of Alzheimer's disease, and the nucleoprotein of
      rabies virus. The conformation of myoglobin is as stable in water as in
      trifluoroethanol, and therefore acted as a negative control. Indeed, the
      recognition of myoglobin did not increase upon increasing the trifluoroethanol
      concentration in the solvent used to apply the antigen to the plate. The
      possibility of imperfect binding to the plastic carrier or nonspecific binding to
      irrelevant antibodies is excluded by using control experiments. We offer the
      first direct evidence that the mAbs recognize the secondary structure of
      epitopes, and that it is possible to correlate the binding conformation of the
      epitopes with CD measurements made in trifluoroethanol-water mixtures.

PMID- 7512606
TI  - In vitro primary responses of human T cells to soluble protein antigens.
AB  - The optimum culture conditions to support in vitro proliferative responses to
      conventional soluble protein antigens by human CD4+ T cells from healthy non
      immunised donors have been determined. These responses were blocked by anti-HLA
      DR monoclonal antibodies (mAbs) and were strictly dependent on the presence of
      antigen-presenting cells (APCs). Primary responses showed a reproducible pattern
      of proliferation kinetics which distinguished them from secondary in vitro T
      cells reactions. T cells specific for the sensitising antigen were recovered from
      primary cultures.

PMID- 7512609
TI  - Distinct functional activities in canine septic shock of monoclonal antibodies
      specific for the O polysaccharide and core regions of Escherichia coli
      lipopolysaccharide.
AB  - Monoclonal antibodies (MAbs) specific for O polysaccharide or core
      oligosaccharide/lipid A of Escherichia coli O111:B4 lipopolysaccharide (LPS) were
      compared in canine septic shock. Animals received O-specific, core-specific, or
      control murine IgG2a MAbs (or saline) before intraperitoneal implantation of an
      E. coli O111:B4-infected clot. Animals were further randomized to ceftriaxone or
      saline. O-specific MAb significantly reduced bacteremia and endotoxemia but not
      serum tumor necrosis factor. Core-specific MAb significantly increased mean
      arterial pressure from day 4 to 28 (P = .02). In dogs not receiving ceftriaxone,
      survival was enhanced by O-specific MAb (4/5) compared with core-specific MAb
      (0/5) and control (1/8) (P = .03). Survival rates were similar (P = .22) but
      survival was prolonged in antibiotic-treated animals also receiving O-specific
      MAb (P = .02 vs. core-specific MAb and controls) or core-specific MAb (P = .08
      vs. controls). These data support the complex role of LPS in sepsis and the
      discrete functional effects of MAbs specific for different elements of LPS.

PMID- 7512610
TI  - Presence of hepatitis B surface antigen (HBsAg)-specific cytotoxic T cells in
      asymptomatic HBsAg carriers.
AB  - To investigate whether there is any evidence of an immune stimulation against
      hepatitis B virus surface antigen (HBsAg) in asymptomatic HBsAg carriers,
      proliferative and cytotoxic responses to HBsAg were measured in their peripheral
      blood lymphocytes. Although the majority of asymptomatic carriers had no
      proliferative response to HBsAg, 3 (25%) of 12 carriers showed significant T cell
      proliferation against HBsAg. In addition, using HBsAg-expressing autologous
      lymphoblastoid cell line (LCL) as target cells, HBsAg-specific cytotoxic activity
      was found in 2 of 3 asymptomatic HBsAg carriers who had a proliferative response
      against HBsAg. Furthermore, 6 cytotoxic T lymphocyte (CTL) clones were isolated
      from 1 asymptomatic carrier. The epitope recognized by 2 CTL clones was mapped to
      the major HBsAg residues 158-172. These CTL clones were able to produce
      interferon-gamma, tumor necrosis factor-alpha, or granulocyte-macrophage colony
      stimulating factor. These findings demonstrate the presence of HBsAg-specific,
      major histocompatibility complex class I-restricted CTL in asymptomatic HBsAg
      carriers.

PMID- 7512608
TI  - Production and characterization of monoclonal antibodies specific for the murine
      T cell receptor zeta chain.
AB  - The T cell receptor (TCR) comprises an antigen-specific alpha beta heterodimer
      non-covalently associated with the CD3 gamma delta epsilon and TCR zeta subunits.
      Both the CD3 and TCR zeta subunits are proposed to be responsible for the
      intracellular signal-transduction events. We report here the production of eight
      monoclonal antibodies (mAbs) that bind in an ELISA assay to a 113 amino acid
      synthetic peptide corresponding to the cytoplasmic domain of TCR zeta. Western
      blot analysis of anti-CD8 precipitates of lysates of transfectants expressing
      chimeric CD8/zeta constructs encoding increasing COOH-terminal truncations of TCR
      zeta indicates that four of these mAbs recognized the region of TCR zeta chain
      comprising the last 29 COOH-terminal residues. Thus, this region of TCR theta may
      encode an immunodominant epitope. Furthermore, one of these mAbs, G3, is capable
      of precipitating both non-phosphorylated and tyrosine phosphorylated TCR zeta.
      The G3 mAb should be useful for elucidating the structural and signalling
      characteristics of the TCR zeta chain.

PMID- 7512611
TI  - Soluble vascular cell adhesion molecule 1 is elevated in patients with Plasmodium
      falciparum malaria.

PMID- 7512612
TI  - Hepatitis C virus infection detected by antibody tests and the polymerase chain
      reaction as a cause of liver dysfunction in renal transplant recipients.
AB  - Hepatitis C infection (HCV) is more prevalent in patients who have received
      kidney transplants than in the general population but the morbidity and mortality
      associated with infection in this group is unclear. Sera taken from 36 renal
      transplant recipients with chronic liver dysfunction and from 42 with normal
      liver function were tested for HCV infection by second generation ELISA (Abbott
      Laboratories) and second generation recombinant immunoblot assay (Chiron
      Corporation) (RIBA-2). Evidence of HCV replication was sought by reverse
      transcription polymerase chain reaction (RT PCR) using primers from the 5'
      nontranslated region (5'NTR). Infection was detected in 20/36 (54%) and in 2/42
      (4.8%) controls (P < 0.01). Twelve liver dysfunction patients were positive by
      all three tests, six were positive by ELISA and RT PCR but had indeterminate RIBA
      2, one was positive by ELISA and RIBA but negative by RT PCR, and one was
      positive only by RT PCR. Of two infected control patients, one was positive by
      all three tests and one who was later found to have been in the early stage of
      infection was positive only by RT PCR. Follow-up of infected patients showed
      persistence of viraemia in 14/15 (93%). Evidence of infection with different
      types of HCV was shown by the lack of amplification by RT PCR by primers with
      mismatching bases with HCV types 2 and 3. It is concluded that in our renal
      transplant patients, chronic HCV infection is usually associated with liver
      dysfunction and persistent infection is common.

PMID- 7512613
TI  - Rapid culture-amplified immunofluorescent test for the detection of human
      rhinoviruses in clinical samples: evidence of a common epitope in culture.
AB  - Ohio HeLa cells in multichamber slides were inoculated with nasal samples from
      patients presenting with common cold symptoms and incubated at 33 degrees C with
      gentle shaking for 48 hours. The cultures were fixed with cold acetone, and viral
      antigens were detected by immunofluorescence using an antirhinovirus type 2 (HRV
      2) polyclonal serum. Of 158 samples, 58 (36.7%) and 57 (36%) were positive for
      HRV by virus isolation (confirmed by acid lability test) and by culture-amplified
      immunofluorescent (CAIF) test, respectively. The correlation between the two
      tests was highly significant (P = 0.0001). Nasal washings or nasal/throat swabs
      were equally suitable for detecting virus by isolation but not by CAIF. On the
      other hand, nasal washings were better than nasal/throat swabs for detecting HRV
      by CAIF. In an ELISA system, the polyclonal anti-HRV-2 serum recognized a
      rhinovirus antigen expressed in situ within 48 hr postinfection by all the 11 HRV
      serotypes investigated. However, 60 hr postinfection, the anti-HRV-2 serum
      recognized only homologous and closely related HRV antigens. These results
      suggest that a rhinovirus "common" antigen may be expressed some 48 hr after
      infection of Ohio HeLa cells with rhinoviruses. The CAIF test provides a
      sensitive, rapid and reliable procedure to detect wild-type rhinovirus infection
      as well as a clear alternative to detection by isolation.

PMID- 7512615
TI  - Long-term foscarnet therapy not associated with the development of foscarnet
      resistant human immunodeficiency virus type 1 in an acquired immunodeficiency
      syndrome patient.
AB  - Sequential human-immunodeficiency virus type 1 (HIV-1) isolates from an acquired
      immunodeficiency syndrome (AIDS) patient on long-term foscarnet and zidovudine
      therapy were examined for the emergence of foscarnet resistance. One isolate
      obtained before therapy, and three post-foscarnet therapy HIV isolates had
      similar foscarnet sensitivity profiles, despite the emergence of foscarnet
      resistant herpes simplex virus type 2 (HSV-2) during the period of therapy.
      Virion reverse transcriptases from these isolates were also equally inhibited by
      foscarnet. In contrast, sequential HIV isolates taken pre- and postzidovudine
      therapy showed a gradual increase in IC50 to this drug. In this patient, long
      term foscarnet and zidovudine therapy selected foscarnet-resistant HSV and
      zidovudine-resistant HIV; in contrast, HIV remained susceptible to foscarnet.
      Concurrent administration of other anti-HIV drugs (zidovudine and interferon
      alpha) may have hindered the development of foscarnet resistant HIV-1 in vivo.

PMID- 7512614
TI  - Natural killer cell responses in renal transplant patients with cytomegalovirus
      infection.
AB  - Natural killer (NK) cell function in relation to immunophenotypical signs of NK
      activation was studied prospectively in 15 renal transplant patients with
      cytomegalovirus (CMV) infection. NK activity (expressed as the percentage of K562
      lysis) before onset of CMV infection reached a median of 6% (range 2-18%),
      comparable to values observed in noninfected controls [7% (range 7-21%), P < .1].
      During CMV infection, NK activity rose to a maximum of 25% (6-60%) (P < .001 vs.
      controls). Maximal values exceeded the upper level of controls in nine of 15
      patients. NK activity was correlated to the number of CD56+HLADR+ cells in the
      peripheral blood (r = .57, P < .001). These data suggest that NK cells play a
      role in the recovery from CMV infection in a substantial number of patients and
      that immunophenotypical analysis of NK activation provides a surrogate marker of
      NK cell function.

PMID- 7512616
TI  - Action of brefeldin A on amphibian neurons: passage of newly synthesized proteins
      through the Golgi complex is not required for continued fast organelle transport
      in axons.
AB  - The relation between the availability of newly synthesized protein and lipid and
      the axonal transport of optically detectable organelles was examined in
      peripheral nerve preparations of amphibia (Rana catesbeiana and Xenopus laevis)
      in which intracellular traffic from the endoplasmic reticulum to the Golgi
      complex was inhibited with brefeldin A (BFA). Accumulation of fast-transported
      radio-labeled protein or phospholipid proximal to a sciatic nerve ligature was
      monitored in vitro in preparations of dorsal root ganglia and sciatic nerve.
      Organelle transport was examined by computer-enhanced video microscopy of single
      myelinated axons. BFA reduced the amount of radiolabeled protein and lipid
      entering the fast-transport system of the axon without affecting either the
      synthesis or the transport rate of these molecules. The time course of the effect
      of BFA on axonal transport is consistent with an action at an early step in the
      intrasomal pathway, and with its action being related to the observed rapid (< 1
      h) disassembly of the Golgi complex. At a concentration of BFA that reduced fast
      transported protein by > 95%, no effect was observed on the flux or velocity of
      anterograde or retrograde organelle transport in axons for at least 20 h.
      Bidirectional axonal transport of organelles was similarly unaffected following
      suppression of protein synthesis by > 99%. The findings suggest that the
      anterograde flux of transport organelles is not critically dependent on a supply
      of newly synthesized membrane precursors. The possibilities are considered that
      anterograde organelles normally arise from membrane components supplied from a
      post-Golgi storage pool, as well as from recycled retrograde organelles.

PMID- 7512617
TI  - Protein kinase C activation attenuates N-methyl-D-aspartate-induced increases in
      intracellular calcium in cerebellar granule cells.
AB  - Activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor
      increases levels of intracellular calcium and can lead to stimulation of protein
      kinase C activity. Several reports have demonstrated that stimulation of protein
      kinase C can, in turn, increase electrophysiological responses to NMDA in certain
      cells or in oocytes expressing certain NMDA receptor subunits. In the present
      study, the effects of protein kinase C activation on NMDA receptor-mediated
      increases in intracellular Ca2+ level were investigated in primary cultures of
      rat cerebellar granule cells using fura-2 fluorescence spectroscopy. Pretreatment
      of the cells with the protein kinase C activator phorbol 12-myristate 13-acetate
      (PMA), but not the inactive analogue 4 alpha-phorbol 12-myristate 13-acetate,
      inhibited NMDA-induced increases in intracellular Ca2+ levels. Coincubation of
      cells with PMA and the kinase inhibitor staurosporine or calphostin C blocked the
      PMA effect. The potency of NMDA was reduced twofold, and the potency of the NMDA
      receptor co-agonist, glycine, to enhance the response to NMDA was decreased
      fourfold by pretreatment of cells with PMA. The effect on glycine was mimicked by
      pretreatment with okadaic acid, a protein phosphatase inhibitor. PMA treatment
      did not significantly alter Mg2+ inhibition of the NMDA response but decreased
      the potency of the competitive antagonist CGS-19755. These data suggest that, in
      cerebellar granule cells, the function of the NMDA receptor may be subject to
      feed-back inhibition by protein kinase C stimulation. Under physiological
      conditions, this inhibition may result from a decreased effectiveness of the
      endogenous co-agonists, glutamate and glycine.

PMID- 7512618
TI  - Evidence that prostaglandin E2 can block calcium-activated 86Rb efflux from rat
      brain synaptosomes via a protein kinase C-dependent mechanism.
AB  - The effects of prostaglandin E2 (PGE2) on 86Rb efflux from rat brain synaptosomes
      were studied to explore its role in nerve ending potassium (K+) channel
      modulation. A selective dose-dependent inhibition of the calcium-activated
      charybdotoxin-sensitive component of efflux was found upon application of PGE2.
      No significant effect was seen on basal and voltage-dependent components over the
      concentration range of 10(-8) to 10(-5) M. The protein kinase C (PKC) inhibitors
      H-7 (10 microM) and staurosporine (100 nM), as well as prolonged preincubation
      (90 min) with 4 beta-phorbol 12,13-dibutyrate, which has been reported to down
      regulate PKC, abolished the PGE2-induced inhibition, whereas HA1004 (10 microM)
      and Rp-3',5'-cyclic phosphorothioate (100 nM), which are relatively more
      selective for protein kinase A than PKC, did not. 4 beta-Phorbol 12,13-dibutyrate
      (100 nM), an activator of PKC, produced a similar inhibition of the Ca(2+)
      dependent component of 86Rb efflux but also had no effect on the basal and
      voltage-dependent components. These data suggest that PGE2 can inhibit rat brain
      nerve ending calcium-activated 86Rb efflux, and this inhibition may involve PKC
      activation.

PMID- 7512619
TI  - Expression of polyubiquitin and heat-shock protein 70 genes increases in the
      later stages of disease progression in scrapie-infected mouse brain.
AB  - We have shown by northern analyses that the expression of the mouse polyubiquitin
      C gene is increased severalfold in the brains of mice infected with both the ME7
      and 87V strains of scrapie. Expression of the polyubiquitin gene does not change
      significantly, compared with controls, until the later stages of disease
      progression when there is a 2.5-fold increase in ME7-infected brains and a 1.8
      fold increase in 87V-infected brains. The patterns of changes of expression of
      the polyubiquitin genes in brains infected with the two strains of scrapie
      resemble those of accumulation of ubiquitin-conjugate-positive structures in the
      brain that are detected immunohistochemically. A similar increase in the
      expression of a heat-shock protein 70 gene also occurs.

PMID- 7512620
TI  - Fate of jimpy-type oligodendrocytes in jimpy heterozygote.
AB  - In the jimpy mutant mouse, as well as in many other animals with mutations in the
      myelin proteolipid protein (PLP) gene, oligodendrocytes degenerate before their
      maturation. To analyze whether this degeneration is caused by the loss of
      function of PLP gene products related to oligodendrocyte maturation/survival
      acting extrinsically, expression of the PLP gene was investigated in the jimpy
      heterozygote, in which one-half of the cells are jimpy type and the other half
      are wild type due to random X-chromosome inactivation. We first showed that jimpy
      PLP gene expression is normally regulated at the early stages of development in
      brains of jimpy hemizygotes and heterozygotes, at least to day 2 after birth.
      However, the great increase in the level of PLP gene transcripts observed in wild
      type mouse brain is suppressed in jimpy mouse brain. This increase was also
      suppressed in the jimpy heterozygote, and by 2 months after birth, very few jimpy
      type PLP gene transcripts were detected in heterozygotes. These results indicate
      that jimpy-type oligodendrocytes cannot survive or are still in the immature
      stage in the brain of jimpy heterozygotes. Thus, degeneration of jimpy
      oligodendrocytes is not caused merely by the lack of trophic factors.

PMID- 7512621
TI  - Tyrosine and serine phosphorylation of dystrophin and the 58-kDa protein in the
      postsynaptic membrane of Torpedo electric organ.
AB  - Dystrophin associates with a 58-kDa and an 87-kDa protein in the postsynaptic
      membrane of the Torpedo electric organ. We have previously shown that the 87-kDa
      protein is a major phosphotyrosine-containing protein in these membranes.
      Immunoprecipitation of the 87-kDa protein from phosphorylated postsynaptic
      membranes results in coimmunoprecipitation of additional phosphorproteins. These
      phosphorproteins are identified as dystrophin and the 58-kDa protein. Monoclonal
      antibodies to dystrophin and the 58-kDa protein immunoprecipitate phosphorylated
      forms of these proteins from postsynaptic membranes phosphorylated in vitro.
      Phosphoamino acid analysis reveals that dystrophin and the 58-kDa protein are
      phosphorylated on serine and tyrosine residues. In addition, both dystrophin and
      the 58-kDa protein are shown to be phosphorylated on tyrosine residues in vivo.
      These results suggest that the synaptic function of dystrophin and its associated
      proteins, the 58-kDa and 87-kDa proteins, may be modulated by tyrosine and serine
      protein phosphorylation.

PMID- 7512622
TI  - Assessing the extent of RNA editing in the TMII regions of GluR5 and GluR6
      kainate receptors during rat brain development.
AB  - Kainate (KA) is a potent neuroexcitatory agent that induces seizure and brain
      damage syndromes with increasing efficiency during maturation. It has been
      suggested that the selective neuronal damage induced by KA may result not only
      from its depolarizing actions, but also from intracellular accumulation of Ca2+.
      The effects of KA are mediated by specific high-affinity receptors, enriched in
      the hippocampus. Members of this class of receptors, GluR5 and GluR6, have been
      characterized by cDNA cloning. Ca2+ permeability of the GluR6 receptor is
      determined by editing in the corresponding RNA. We report here a rapid PCR-based
      approach to assess in all experimental conditions the levels of GluR5 and GluR6
      editing in the transmembrane TMII region. We show that editing in both GluR5 and
      GluR6 RNA is developmentally regulated and that different regions of the adult
      rat hippocampus demonstrate distinct levels of GluR6 editing.

PMID- 7512623
TI  - Ohioensins and pallidisetins: novel cytotoxic agents from the moss Polytrichum
      pallidisetum.
AB  - Bioassay-directed fractionation of an EtOH extract of the moss Polytrichum
      pallidisetum (Polytrichaceae) led to the isolation of three novel
      benzonaphthoxanthenones, 1-O-methylohioensin B [6], 1-O-methyldihydroohioensin B
      [7] and 1,14-di-O-methyldihydroohioensin B [8], and two novel cinnamoyl
      bibenzyls, pallidisetin A [9] and pallidisetin B [10]. Their structures and
      relative stereochemistry were established by spectral analyses and chemical
      correlation. Compounds 6-10 exhibited cytotoxic activity against the human tumor
      cell lines RPMI-7951 melanoma and U-251 glioblastoma multiforme. These two types
      of compounds could hypothetically be derived from cinnamic acid and bibenzyls
      through different biogenetic pathways.

PMID- 7512624
TI  - Brain glucose utilisation in acquired childhood aphasia associated with a sylvian
      arachnoid cyst: recovery after shunting as demonstrated by PET.
AB  - Regional brain glucose utilisation was investigated with PET and
      fluorodeoxyglucose (FDG) in a case of epileptic aphasia (Landau-Kleffner
      syndrome) associated with a left sylvian arachnoid cyst. CT and MRI had failed to
      disclose any mass effect of the cyst on surrounding brain structures. Sequential
      metabolic measurements showed a comparable pronounced hypometabolism in cortical
      regions around the cyst, involving speech areas, and suggested mild but chronic
      compression of the developing brain. After placement of a cyst-peritoneal shunt
      system, significant metabolic improvement occurred in all cortical regions,
      especially the inferior frontal gyrus and the perisylvian area, with predominant
      residual deficit in the left superior temporal gyrus. These findings were
      correlated with a pronounced increase in word fluency and slower progress in
      verbal auditory comprehension. This report suggests that PET is able to evaluate
      the functional disturbances associated with expanding arachnoid cysts, and to
      follow the neurological improvement after drainage.

PMID- 7512626
TI  - Modulatory influence of putative inhibitors of nitric oxide synthesis on visual
      processing in the cat lateral geniculate nucleus.
AB  - 1. Using an in vivo preparation we have examined the actions of two inhibitors of
      nitric oxide synthase (NOS), NG-nitro-L-arginine (L-NOArg) and NG-methyl-L
      arginine (L-MeArg), in the feline dorsal lateral geniculate nucleus (dLGN). We
      compared the responses obtained to iontophoretic application of these substances
      during visual stimulation with those elicited by visual stimulation alone. The
      effects of concurrent ejection of L-arginine (L-Arg), the normal physiological
      substrate of NOS, and D-arginine, the inactive isomer, were tested on these
      responses. 2. Extracellular application of L-NOArg and L-MeArg produced clear and
      repeatable effects, consisting of substantial reduction in discharge rate without
      affecting response selectivity, on 94% of tested cells. These effects were
      prevented by simultaneous application of L-Arg, which when ejected alone produced
      no change on visual evoked responses. 3. The data suggest that nitric oxide (NO)
      is necessary for the transmission of the visual input under normal visual
      stimulation and show a direct involvement of NO in visual information processing
      at the level of dLGN, suggesting that its contribution to brain mechanisms is
      more profound than previously thought.

PMID- 7512625
TI  - Characteristics and postnatal development of a hyperpolarization-activated inward
      current in rat hypoglossal motoneurons in vitro.
AB  - 1. Single-electrode voltage clamp recordings in a rat brain stem slice
      preparation were used to determine the characteristics and postnatal development
      of a hyperpolarization-activated inward current (Ih) in hypoglossal motoneurons
      (HMs). 2. In young adult HMs (> P21), a noninactivating, time- and voltage
      dependent inward current was evident during hyperpolarizing voltage steps to
      membrane potentials negative to approximately -65 mV from depolarized holding
      potentials [Vh = -56.2 +/- 1.0 (SE) mV]. The averaged reversal potential (Erev)
      of the inward current, estimated using an extrapolation procedure, was -38.8 +/-
      2.9 mV (n = 5), suggesting that a mixed cationic current underlies inward
      rectification in HMs. 3. The voltage dependence of Ih activation was determined
      from tail current relaxations that followed a family of voltage steps to
      different membrane potentials. Normalized tail current amplitudes were well
      fitted with a single Boltzman function with a half-activation at -79.8 +/- 0.7 mV
      and slope factor = 5.3 +/- 0.3 (n = 8). 4. Time constants of Ih activation and
      deactivation were voltage-dependent. Activation proceeded more quickly with
      larger hyperpolarizing voltage steps; time constants averaged 389, 181, and 134
      ms at -69, -82, and -95 mV, respectively (n = 6). Ih deactivated during
      depolarizing voltage steps from hyperpolarized holding potentials. Deactivation
      was faster with larger depolarizing steps; time constants averaged 321, 215, and
      107 ms at -80, -71, and -62 mV, respectively (n = 4). 5. Ih was sensitive to
      extracellular cesium but relatively insensitive to extracellular barium. The
      current amplitude near half-activation (approximately -84 mV) was almost
      completely blocked (to 11% of control) by Cs+ (3 mM, n = 3) but was reduced to
      only 85 and 60% in 0.5 (n = 2) and 2 mM Ba2+ (n = 3), respectively. 6. There was
      a marked increase in the amplitude of Ih during postnatal development of HMs.
      Measured near half-activation, Ih was approximately 10-fold larger in adult (> or
      = P21; n = 20) than in neonatal HMs (< or = P8; n = 7). Input conductance (GN)
      was only threefold higher in the same sample of HMs. There were no apparent
      differences in the voltage dependence or Erev of Ih between neonatal and older
      HMs. These results suggest that the increased amplitude of Ih results from an
      increase in Ih current density.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7512628
TI  - Simulator for neural networks and action potentials: description and application.
AB  - 1. We describe a simulator for neural networks and action potentials (SNNAP) that
      can simulate up to 30 neurons, each with up to 30 voltage-dependent conductances,
      30 electrical synapses, and 30 multicomponent chemical synapses. Voltage
      dependent conductances are described by Hodgkin-Huxley type equations, and the
      contributions of time-dependent synaptic conductances are described by second
      order differential equations. The program also incorporates equations for
      simulating different types of neural modulation and synaptic plasticity. 2.
      Parameters, initial conditions, and output options for SNNAP are passed to the
      program through a number of modular ASCII files. These modules can be modified by
      commonly available text editors that use a conventional (i.e., character based)
      interface or by an editor incorporated into SNNAP that uses a graphical
      interface. The modular design facilitates the incorporation of existing modules
      into new simulations. Thus libraries can be developed of files describing
      distinctive cell types and files describing distinctive neural networks. 3.
      Several different types of neurons with distinct biophysical properties and
      firing properties were simulated by incorporating different combinations of
      voltage-dependent Na+, Ca2+, and K+ channels as well as Ca(2+)-activated and
      Ca(2+)-inactivated channels. Simulated cells included those that respond to
      depolarization with tonic firing, adaptive firing, or plateau potentials as well
      as endogenous pacemaker and bursting cells. 4. Several types of simple neural
      networks were simulated that included feed-forward excitatory and inhibitory
      chemical synaptic connections, a network of electrically coupled cells, and a
      network with feedback chemical synaptic connections that simulated rhythmic
      neural activity. In addition, with the use of the equations describing electrical
      coupling, current flow in a branched neuron with 18 compartments was simulated.
      5. Enhancement of excitability and enhancement of transmitter release, produced
      by modulatory transmitters, were simulated by second-messenger-induced modulation
      of K+ currents. A depletion model for synaptic depression was also simulated. 6.
      We also attempted to simulate the features of a more complicated central pattern
      generator, inspired by the properties of neurons in the buccal ganglia of
      Aplysia. Dynamic changes in the activity of this central pattern generator were
      produced by a second-messenger-induced modulation of a slow inward current in one
      of the neurons.

PMID- 7512627
TI  - Variation in IH, IIR, and ILEAK between acutely isolated adult rat dorsal root
      ganglion neurons of different size.
AB  - 1. The distribution of IH, IIR, and ILEAK was studied in different diameter rat
      dorsal root ganglion (DRG) neuron cell bodies (neurons). DRG neurons were studied
      in three diameter ranges: small (19-27 microns), medium (33-37 microns), and
      large (44-54 microns). IH was defined as a slowly activating inward current
      evoked by hyperpolarizing voltage steps from a holding potential (HP) of -60 mV,
      and blocked by 1 mM Cs2+ but not 1 mM Ba2+. Inward rectifier current (IIR) was
      defined as a rapidly activating current evoked by hyperpolarizations from HP -60
      mV, which rectified inwardly around the reversal potential for potassium (EK),
      and was completely blocked by 100 microM Ba2+. ILEAK was defined as an outward
      resting current at HP -60 mV, which did not rectify and was blocked by 100 microM
      Ba2+ but not by 2 mM Cs+. 2. IH was observed in 23 of 23 large, 11 of 12 medium,
      and in 9 of 20 small diameter DRG neurons tested. Peak IH normalized to membrane
      surface area was significantly greater in large than in medium or small diameter
      DRG neurons expressing IH. All neurons exhibiting IH under voltage clamp
      conditions had short duration action potentials and exhibited time-dependent
      rectification under current clamp conditions, properties similar to A-type DRG
      neurons. The 11 small diameter neurons not expressing IH had long duration action
      potentials and did not exhibit time-dependent rectification, properties similar
      to C-type DRG neurons. 3. IIR was detected in 18 of 22 medium diameter neurons
      tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512629
TI  - An active membrane model of the cerebellar Purkinje cell. I. Simulation of
      current clamps in slice.
AB  - 1. A detailed compartmental model of a cerebellar Purkinje cell with active
      dendritic membrane was constructed. The model was based on anatomic
      reconstructions of single Purkinje cells and included 10 different types of
      voltage-dependent channels described by Hodgkin-Huxley equations, derived from
      Purkinje cell-specific voltage-clamp data where available. These channels
      included a fast and persistent Na+ channel, three voltage-dependent K+ channels,
      T-type and P-type Ca2+ channels, and two types of Ca(2+)-activated K+ channels.
      2. The ionic channels were distributed differentially over three zones of the
      model, with Na+ channels in the soma, fast K+ channels in the soma and main
      dendrite, and Ca2+ channels and Ca(2+)-activated K+ channels in the entire
      dendrite. Channel densities in the model were varied until it could reproduce
      Purkinje cell responses to current injections in the soma or dendrite, as
      observed in slice recordings. 3. As in real Purkinje cells, the model generated
      two types of spiking behavior. In response to small current injections the model
      fired exclusively fast somatic spikes. These somatic spikes were caused by Na+
      channels and repolarized by the delayed rectifier. When higher-amplitude current
      injections were given, sodium spiking increased in frequency until the model
      generated large dendritic Ca2+ spikes. Analysis of membrane currents underlying
      this behavior showed that these Ca2+ spikes were caused by the P-type Ca2+
      channel and repolarized by the BK-type Ca(2+)-activated K+ channel. As in
      pharmacological blocking experiments, removal of Na+ channels abolished the fast
      spikes and removal of Ca2+ channels removed Ca2+ spiking. 4. In addition to
      spiking behavior, the model also produced slow plateau potentials in both the
      dendrite and soma. These longer-duration potentials occurred in response to both
      short and prolonged current steps. Analysis of the model demonstrated that the
      plateau potentials in the soma were caused by the window current component of the
      fast Na+ current, which was much larger than the current through the persistent
      Na+ channels. Plateau potentials in the dendrite were carried by the same P-type
      Ca2+ channel that was also responsible for Ca2+ spike generation. The P channel
      could participate in both model functions because of the low-threshold K2-type
      Ca(2+)-activated K+ channel, which dynamically changed the threshold for
      dendritic spike generation through a negative feedback loop with the activation
      kinetics of the P-type Ca2+ channel. 5. These model responses were robust to
      changes in the densities of all of the ionic channels.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7512630
TI  - Multiple high-threshold calcium currents in acutely isolated rat amygdaloid
      pyramidal cells.
AB  - 1. High-threshold Ca2+ currents were studied in large pyramidal cells acutely
      dissociated from the rat amygdaloid complex. L-, N-, and P-type currents were
      present in about equal proportions in these cells and accounted for most of the
      whole-cell current.

PMID- 7512631
TI  - Subplate pioneers and the formation of descending connections from cerebral
      cortex.
AB  - The adult cerebral cortex extends axons to a variety of subcortical targets,
      including the thalamus and superior colliculus. These descending projections are
      pioneered during development by the axons of a transient population of subplate
      neurons (McConnell et al., 1989). We show here that the descending axons of
      cortical plate neurons appear to be delayed significantly in their outgrowth,
      compared with those of subplate neurons. To assess the possible role of subplate
      neurons in the formation of these pathways, subplate neurons were ablated during
      the embryonic period. In all cases, an axon pathway formed from visual cortex
      through the internal capsule and into the thalamus. In half of all cases,
      however, cortical axons failed to invade their normal subcortical targets. In the
      other half, targets were innervated normally. Subplate neurons are therefore
      likely to provide important cues that aid the process by which cortical axons
      grow toward, select, and invade their subcortical targets.

PMID- 7512632
TI  - Effects of excitotoxic lesions of the septum and vertical limb nucleus of the
      diagonal band of Broca on conditional visual discrimination: relationship between
      performance and choline acetyltransferase activity in the cingulate cortex.
AB  - Four experiments examined the role of the cholinergic projections from the septum
      and vertical limb nucleus of the diagonal band of Broca (VDB) in acquisition and
      performance of a conditional visual discrimination. In experiments 1-3,
      excitotoxic lesions were made of the septum and VDB in rats using quisqualic
      acid, which resulted in significant reductions in ChAT activity in the
      hippocampus and cingulate cortex, but with no effects on cortical monoamines. In
      experiment 1, there were significant impairments in acquisition of the
      conditional discrimination, which did not result from motivational impairments.
      Experiment 2 repeated these results with lesion parameters, which produced
      variable effects on hippocampal and cingulate ChAT activity. Those rats with
      reductions in predominantly cingulate ChAT were most impaired in acquisition, but
      those with predominantly hippocampal reductions were relatively unimpaired.
      Experiment 3 showed that quisquate-induced lesions of the VDB, but not of the
      more caudal VDB and horizontal limb nucleus of the diagonal band, produced
      deficits, and a model incorporating the results of experiments 1-3 showed a
      highly significant correlation between errors of commission and cingulate
      cortical ChAT activity (r = -0.82, p < 0.001). Experiment 4 used the excitotoxin
      AMPA to lesion the VDB in rats pretrained on a modified form of the conditional
      discrimination task. In one subgroup of rats this excitotoxin produced profound
      and regionally selective reductions in ChAT activity. This subgroup was also
      impaired in relearning the discrimination to criterion. Again, there was a
      significant inverse relationship between the number of errors of commission made
      in relearning the discrimination and cingulate ChAT activity (r = -0.94, p <
      0.001). These experiments suggest that excitotoxic lesions of the septum/VDB
      produce deficits in conditional discrimination learning and performance, and that
      the integrity of the projection to the cingulate cortex is more crucial than that
      to the hippocampus in this effect. Moreover, there is a close relationship
      between discrimination performance and cholinergic function in the cingulate
      cortex. In conjunction with other results, these data suggest that different
      aspects of cognition and memory are modulated by cholinergic activity in
      different cortical regions.

PMID- 7512633
TI  - A single transmitter regulates gene expression through two separate mechanisms:
      cholinergic regulation of phenylethanolamine N-methyltransferase mRNA via
      nicotinic and muscarinic pathways.
AB  - ACh regulates the gene encoding phenylethanolamine N-methyltransferase (PNMT) in
      bovine adrenal chromaffin cells. In addition to stimulating catecholamine release
      from these cells, cholinergic agents elevate transcription of the PNMT gene.
      Carbachol, which activates both nicotinic and muscarinic receptors, produces 12
      19-fold increases in PNMT mRNA and a 22-fold increase in epinephrine release.
      Selective nicotinic and muscarinic antagonists (hexamethonium and atropine) each
      partially reduce carbachol-stimulated increases in PNMT mRNA while a combination
      of both eliminates > 90% of the carbachol response, thus indicating that
      separable nicotinic and muscarinic components contribute to the cholinergic
      increase in PNMT mRNA. Muscarine alone produces a dose-dependent increase (mean
      sixfold) in steady state PNMT mRNA levels and stimulates the rate of
      transcription fivefold. Only atropine and the m3-m4-selective muscarinic
      antagonist 4-diphenylacetoxy-4-methyl-piperidine (4-DAMP) reduce the response to
      muscarine, strongly suggesting that the m4 receptor is crucial for PNMT mRNA
      activation. In these chromaffin cells, muscarine inhibits adenylate cyclase,
      antagonist bind with affinities characteristic of m4 receptors, and cDNA
      hybridization detects only m4 mRNAs (Fernando et al., 1991). Nicotine also
      induces a dose-dependent increase (mean of 8.5-fold) in PNMT mRNA levels. The
      importance of voltage-gated Ca2+ channels in the nicotine effect is demonstrated
      by the stimulatory effects of calcium ionophores on PNMT mRNA levels (two-to
      fivefold increase) and the ability of the L- and N-type channel blockers
      nifedipine and omega-conotoxin to decrease the nicotine response (by 60% and 40%,
      respectively). Nuclear "run-on" assays further reveal that nicotine enhances
      transcription of the PNMT gene (approximately fourfold). Thus, this study
      provides the first demonstration that both nicotinic and muscarinic stimulation
      modify genomic responses of bovine adrenergic chromaffin cells and identifies
      possible mechanisms.

PMID- 7512634
TI  - Both open and closed NMDA receptor channels desensitize.
AB  - Desensitization of NMDA receptors was studied at the single-channel level using
      outside-out patches taken from rat hippocampus CA neurons maintained short term
      in culture. The amount of desensitization that accumulated as a function of time
      during the application of NMDA (2.5 microM) was measured by the response to the
      rapid application of NMDA at a high concentration (100 microM). Records were
      sorted into two classes: those in which no openings were detected during the
      application of 2.5 microM NMDA, and those in which some channel openings
      occurred. Analysis of these data reveals that some desensitization accumulated
      when no channels opened, but that more desensitization developed when channels
      opened. The observations indicate that channels can pass from the closed state to
      the desensitized state, but that desensitization occurs more rapidly from the
      open state.

PMID- 7512635
TI  - Increased levels of hemoglobin-derived and other peptides in Alzheimer's disease
      cerebellum.
AB  - Several studies point to the importance of peptides and proteolysis in
      Alzheimer's disease (AD). Because of its ability to study small proteins and
      peptides, reverse-phase HPLC was employed to study these species in AD.
      Cerebellum was chosen for these initial studies because it does not show
      significant neuronal loss but does show some pathology in AD. Examination of over
      600 peptide peaks per case revealed 15 that were elevated in AD. Nine were
      fragments of hemoglobin, and the remainder included two species of calmodulin,
      two of myelin basic protein, and one each of 67 kDa neurofilament protein and PEP
      19. The cleavage sites on hemoglobin were after hydrophobic residues and
      immunolocalization was seen preferentially around blood vessel walls and granule
      cells. The elevation of the non-serum-derived peptides was characteristic of
      general metabolic changes that occurred in AD cerebellum, and the presence of
      elevated hemoglobin polypeptides indicated either possible disruption of the
      blood-brain barrier or selective evasion of it by peptidaceous products. Further
      studies are required to establish whether hemoglobin fragments have a role in
      neurodegenerative processes such as AD.

PMID- 7512636
TI  - Endogenous ganglioside GM1 modulates L-type calcium channel activity in N18
      neuroblastoma cells.
AB  - Digital imaging fluorescence microscopy was used to investigate the effect of the
      B subunit of cholera toxin on calcium homeostasis in neuroblastoma N18 cells. The
      B subunit, which binds specifically to ganglioside GM1 in the outer leaflet of
      the cell membrane, was found to induce a sustained increase of intracellular
      calcium concentration ([Ca2+]i). The increase in [Ca2+]i was not observed in the
      absence of extracellular calcium, or in the presence of the calcium chelator
      EGTA, and was blocked by nickel. The B subunit was also found to induce an influx
      of manganese ions, as indicated by a quench of the intracellular fura-2
      fluorescence. These data suggest that the B subunit induces an increase in
      calcium influx in N18 cells. Potassium-induced depolarization also stimulated
      manganese influx; however, after the onset of depolarization-induced influx, the
      B subunit had no further effect. This occlusion suggests involvement of voltage
      dependent calcium channels. Treatment with BayK8644, a dihydropyridine agonist
      selective for L-type calcium channels, induced manganese influx that was not
      altered by the B subunit and apparently blocked the effect of the B subunit
      itself. Furthermore, the dihydropyridine L-type channel antagonists niguldipine
      or nicardipine completely inhibited B subunit-induced manganese influx. Thus, the
      B subunit-induced manganese influx is likely due to activation of an L-type
      voltage-dependent calcium channel. Spontaneous influx of manganese ions was also
      inhibited by nicardipine or niguldipine and by exogenous gangliosides.
      Ganglioside GM1 was more potent than GM3, but globoside had no significant
      effect. The modulation of L-type calcium channels by endogenous ganglioside GM1
      has important implications for its role in neural development, differentiation,
      and regeneration and also for its potential function in the electrical
      excitability of neurons.

PMID- 7512638
TI  - Nitric oxide-dependent and -independent mechanisms of vasodilation in pregnancy.

PMID- 7512637
TI  - AMPA-induced excitotoxic lesions of the basal forebrain: a significant role for
      the cortical cholinergic system in attentional function.
AB  - The aim of the present study was to clarify the role of the basal forebrain (BF)
      cortical cholinergic system in visual attentional function by investigating the
      effect of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
      induced lesions of the basal forebrain on performance of a five-choice serial
      reaction time task. AMPA lesions in the present study produced a profound effect
      on performance of the task, as measured by choice accuracy and correct response
      latency. This deficit was significantly greater than that observed in earlier
      studies following ibotenate- or quisqualate-induced lesions of the BF. However,
      detailed histological and biochemical analysis revealed three rather different BF
      lesions depending upon the batch of AMPA supplied. In one group of animals (BF/1)
      the deficits in task performance were substantially greater and longer lasting
      compared to another group of lesioned animals (BF/2), which showed behavioral
      recovery several months following the lesion. The former sustained severe
      pallidal damage in addition to marked reductions in cortical ChAT activity.
      Support for the attentional nature of these deficits was obtained by the ability
      to improve task performance in BF/1 lesioned animals by increasing the duration
      of the visual stimulus and thus reducing the attentional load placed on these
      animals. In contrast, performance deficits could be reinstated in those animals
      showing behavioral recovery (BF/2) by reducing the duration of the visual
      stimulus and thus increasing attentional load. In the second experiment more
      discrete lesions of the magnocellular cholinergic neurons were made, resulting in
      extensive reduction of cortical ChAT activity with considerably less neuronal
      loss from the dorsal pallidum compared to the BF/1 lesion group. Once again,
      deficits on the task were substantially greater than observed previously
      following either quisqualate- or ibotenate-induced BF lesions. Furthermore, the
      cholinergic specificity of these deficits was supported by the attenuation of
      behavioral impairments following administration of the anti-cholinesterase
      physostigmine. Taken together with our earlier work, which has failed to
      demonstrate mnemonic deficits following lesions to the magnocellular neurons of
      the nucleus basalis of Meynert, these results suggest that the most consistent
      deficit produced following lesions of the BF-cortical cholinergic system is
      attentional dysfunction Analogous deficits in visual attention are also seen in
      patients with Alzheimer's disease, which can also be improved by anti
      cholinesterase treatment.

PMID- 7512639
TI  - Altered histochemical staining with reduced nicotinamide adenine dinucleotide
      phosphate diaphorase in Mongolian gerbil brain after cerebral ischemia.

PMID- 7512640
TI  - Reversal of left ventricular hypertrophy with different classes of drugs causes
      differing ventricular biochemical changes.

PMID- 7512641
TI  - Bradykinin prevents left ventricular hypertrophy in rats.

PMID- 7512643
TI  - Beta 1 and beta 4 integrin expression in methacarn and formalin-fixed material
      from in situ ductal carcinoma of the breast.
AB  - The integrins are alpha beta heterodimeric transmembrane proteins mediating cell
      substratum as well as cell-cell interactions. Previous distribution studies on
      integrin expression have been limited by the requirement of cryostat sectioned
      tissues, and consequent poor resolution. We have examined 40 examples of ductal
      carcinoma in situ (DCIS) for the expression of both beta 1 and beta 4 integrin
      chains. These showed strong polarized membrane staining of residual myoepithelial
      cells (correlating with expression of smooth muscle specific actin) and of the
      basement membrane region with beta 1 and beta 4 antibodies respectively. In 12
      out of 40 cases, the DCIS was negative for the beta 1 chain and a variable
      pattern of reactivity was seen in the remaining cases. The beta 4 chain was
      detected focally and weakly in the tumour cells of 7/40 DCIS and strongly in one;
      all of these cases were also positive for the beta 1 chain. Of the 22 cases where
      co-existent invasion was present, the infiltrating component showed either a
      similar degree or a diminution of the extent of immunostaining when compared with
      the in situ component; only one showed enhanced staining (beta 1 only). This
      study demonstrates that two of the main beta chains, beta 1 and beta 4, can be
      effectively demonstrated on methacarn and cold (4 degrees C) formalin-fixed
      tissues by avidin-biotin indirect immunoperoxidase staining and that the results
      are similar to those achieved using frozen tissue.

PMID- 7512644
TI  - Induction of nitric oxide synthase in the neo-vasculature of experimental tumours
      in mice.
AB  - Maintenance of blood flow is an important factor in sustaining tumour growth.
      Functional studies have previously demonstrated a reduction in tumour blood flow
      with selective inhibitors of nitric oxide (NO) synthesis, L-NAME (NG-nitro-L
      arginine-methylester) and L-NMMA (NG-monomethyl-L-arginine), when administered
      locally to tumours derived from murine colon 26 adenocarcinoma and B16 melanoma
      cells. The type of NO synthase which might be responsible for this locally
      derived NO and the site of synthesis was not described. Here we have investigated
      the distribution of immunoreactivity and the biochemical characteristics of the
      enzymes synthesizing NO in the same murine model. Adenocarcinoma (colon 26) or
      melanoma (B16) cells were introduced into a sponge matrix implanted
      subcutaneously in mice. After 7, 12, and 14 days, the implants were removed and
      frozen sections were immunostained with rabbit antisera to constitutive and
      inducible isoforms of NO synthase. Immunoreactivity with antisera to inducible NO
      synthase was detected in the vasculature of neoplastic implants, with and without
      the sponge, at 12 and 14 days. The enzyme was not evident in 7-day-old tumours,
      in non-neoplastic implants, in areas of tissue outside the tumour, or in
      adenocarcinoma or melanoma cells. Enzyme activity was measurable in homogenates
      of neoplastic implants removed at day 7 and was found to be Ca2+/calmodulin
      independent. Immunoreactivity with antisera to inducible NO synthase was seen
      principally in the endothelium of newly-formed capillaries, identified by
      immunostaining for von Willebrand factor in serial sections. Immunoreactivity
      with antiserum to constitutive NO synthase was not evident in either neoplastic
      or non-neoplastic implants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512642
TI  - Deranged CD44 gene activity in malignancy.

PMID- 7512646
TI  - Immunolocalization of fibronectin and vitronectin receptors in human gingival
      fibroblasts spreading on titanium surfaces.
AB  - The adhesion and spreading of human gingival fibroblasts on glass and differently
      processed titanium surfaces was studied by immunolocalization of vinculin and the
      alpha and beta subunits of the fibronectin (alpha 5 beta 1) and (alpha v beta 3)
      receptors. Vinculin-containing focal contacts were present both at 4 and 24 h of
      spreading in cells grown on glass or electropolished or etched titanium surfaces
      but not in cells spreading on sandblasted titanium surfaces. Immunostaining for
      the alpha 5 and beta 1 subunits of the fibronectin receptor showed only a diffuse
      membrane fluorescence after 4 h of cell spreading irrespective of the growth
      surface. The alpha v and beta 3 subunits of the vitronectin receptor were at this
      stage detected in focal contacts in cells spreading on glass or electropolished
      or etched titanium surfaces. In cells spreading on sandblasted titanium surfaces,
      however, the vitronectin receptor had only a diffuse distribution. In cells that
      had been allowed to spread for 24 h on glass or electropolished or etched
      titanium surfaces the alpha 5 and beta 1 integrin subunits were either diffusely
      distributed or showed a localization typical of extracellular matrix contacts.
      The alpha v and beta 3 integrin subunits were, as earlier, localized to typical
      focal contacts in cells grown on glass or electropolished or etched titanium
      surfaces. Cells attached to sandblasted titanium surfaces still expressed all the
      integrin subunits only diffusely. The results show that the surface texture of
      the substratum can affect the expression of integrin subunits in human gingival
      fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512647
TI  - Immunohistochemical analysis of tissues regenerated from within periodontal
      defects treated with expanded polytetrafluoroethylene membranes.
AB  - Immunocytochemical analysis was carried out on samples of 5-, 6-, and 9-week old
      regenerated soft tissue taken from healing periodontal defects treated by guided
      tissue regeneration using expanded polytetrafluorethylene (ePTFE) membranes. A
      panel of monoclonal and polyconal antibodies to cytokeratins, vimentin, and
      collagen was used to label cells and collagen types I, III, and IV. Epithelium
      was identified in 7 of the 9 samples examined, in addition to mesenchymal cells
      staining positively for vimentin and co-distribution of collagen types I, III,
      and IV in all samples. Clinical observations indicated that exposure of the ePTFE
      membranes during healing was a frequent occurrence, and the presence and quantity
      of epithelium found within the healing defect beneath the membrane may be related
      to the extent to which this occurs.

PMID- 7512645
TI  - Isolation of naturally processed peptides from a Toxoplasma gondii-infected human
      B lymphoma cell line that are recognized by cytotoxic T lymphocytes.
AB  - Naturally processed peptides derived from Toxoplasma gondii (T. gondii) were acid
      extracted from T. gondii-infected cells and detected by cytotoxic T lymphocytes
      (CTL) derived from peripheral blood lymphocytes of a patient with chronic
      toxoplasmosis. The CTL lines were obtained by weekly in vitro stimulation with a
      T. gondii-infected human B cell lymphoma line, ARH, which shares HLA-A2 and -Cw4
      determinants with the patient. The lytic activity of these CTL lines against T.
      gondii-infected ARH and ARH pulsed with fraction 29 of a reversed-phase high
      performance liquid chromatography (HPLC) extract from T. gondii-infected ARH was
      inhibited by an anti-HLA-A, B, C monoclonal antibody (mAb) and an anti-HLA-A2
      mAb. Anti-HLA-DR mAb failed to block the lytic activity. Thus, the presentation
      of peptides by T. gondii-infected cells for CTL is mediated by HLA-A2 molecules.
      Interestingly, antigen presentation of ARH pulsed with naturally processed HPLC
      fraction 29 peptides was not inhibited by treatment with brefeldin A. The amino
      acid sequence of the HLA-A2-bound peptide in fraction 29 was in part consistent
      with the predictive algorithm of HLA-A2-binding peptide motifs.

PMID- 7512648
TI  - Synthesis and inverse emulsion polymerization of aminated acrylamidodextran.
AB  - A chemically modified form of dextran was prepared, having a polymerizable moiety
      (acrylamide) and a reactive functional group (primary amine). Dextran was
      activated with 4-nitrophenyl-chloroformate (24 mol per polysaccharide, 9.8 mol
      per 100 glucose residues); 9.8% glucose residues were converted to aliphatic
      carbonates and 5.2% were converted to cyclic carbonates. The activated dextran
      was coupled with trityldiaminoethane (8 mol per 100 glucose residues),
      reactivated with 4-nitrophenylchloroformate, then coupled with
      acryloamidodiaminohexane (6.8 mol per 100 glucose residues). The trityl group was
      removed by hydrolysis with trifluoroacetic acid to yield the required aminated
      acryloamidodextran. The modified dextran was shown to be polymerizable by inverse
      emulsion polymerization. Submicron particles were successfully prepared,
      containing functional amine groups suitable for preparing drug conjugates or for
      modifying the surface properties of this biomaterial.

PMID- 7512649
TI  - Potent antinociceptive activity of a hydroalcoholic extract of Phyllanthus
      corcovadensis.
AB  - This study analyses the analgesic effect of a hydroalcoholic extract (HE) from
      Phyllanthus corcovadensis in several models of pain in mice. HE (3-60 mg kg-1,
      i.p.) or (100-500 mg kg-1, p.o.) caused a graded and potent analgesic effect
      against the abdominal constriction response caused by acetic acid and
      acetylcholine with an ID50 of about 3 and 100 mg kg-1, respectively. In the tail
      flick model HE (up to 500 mg kg-1, p.o.) was without effect, while morphine (1-10
      mg kg-1, s.c.) caused a graded increase in pain latency (ID50, 3 mg kg-1). HE (1
      300 mg kg-1) given both intraperitoneally and orally caused a potent and graded
      inhibition of the second phase of formalin-induced persistent pain in mice with
      an ID50 of 1 and 80 mg kg-1, respectively. In contrast, morphine (1-5 mg kg-1,
      s.c.) inhibited both phases of formalin-induced pain with an ID50 of 2.5 mg kg-1.
      Indomethacin (1-10 mg kg-1, i.p.) only inhibited the second phase of formalin
      induced pain with an ID50 of about 3 mg kg-1. The analgesic effect of
      indomethacin, but not that caused by morphine and HE was accompanied by a graded
      inhibition of formalin-induced mouse paw oedema. In addition, HE up to 1 g kg-1
      failed to prevent carrageenan- and dextran-induced rat hindpaw oedema. It is
      concluded that HE exhibits a potent antinociceptive profile, either when given
      intraperitoneally or orally.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512650
TI  - Guidelines for developing a research poster for presentation.

PMID- 7512651
TI  - How long is your waiting list? Experience of a urological waiting list
      initiative.
AB  - Experience with a urological waiting list initiative is presented, wherein a list
      of 231 non-urgent cases was cleared over a 5 month period by a single operator.
      Some patients had waited 10 years for surgery. Following a postal request, the
      waiting list was validated; 31.2% of patients wished to be removed. The remaining
      68.8% desired surgery and consisted of 51 requiring minor surgical procedures and
      108 who needed more major surgery mostly for the relief of bladder outflow
      obstruction. Minor cases received dates for surgery; however, only 68.2% of this
      group attended despite being given more than one date for admission. Major cases
      were reviewed in a pre-admission clinic. General and urological condition was
      assessed, improved where necessary and surgery booked or delayed accordingly. A
      small number of patients did not attend or only attended to be reassured that
      surgery was not needed. Following clinical review, 18.5% of this group did not
      require operation. The long urological waiting list is a unique situation where
      patients listed may no longer require surgery. Reviewing these patients not only
      reduces numbers but also markedly increases percentage attendance for surgery.

PMID- 7512652
TI  - Thermodynamics of RNA folding in a conserved ribosomal RNA domain.
AB  - A small, 58 nt domain of the large subunit ribosomal RNA (Escherichia coli
      sequence 1051 to 1108) is a highly conserved junction of three helices whose
      secondary structure has been established by phylogenetic comparisons. To detect
      any contributions of additional tertiary interactions, the thermal denaturation
      of the rRNA domain was followed by either UV hyperchromicity or calorimetry in
      buffers containing a wide range of Mg2+ concentrations. Several smaller fragments
      corresponding to two different hairpin stem-loop structures within the domain
      were also synthesized and melted for comparison with the larger molecule. A model
      of the secondary structure unfolding was devised, based on measured enthalpies
      and melting temperatures of the component hairpins and tabulated parameters of
      base-pair stacking and loop closure. The model closely simulates the observed
      melting data when three additional factors are included: two parameters to
      account for coaxial stackings within a junction of helices, and a set of
      undefined "tertiary" interactions that unfolds before the secondary structure and
      is preferentially stabilized by Mg2+. A critical feature of this model is a
      conserved pair, U1082/A1086, that is within the junction loop and hypothesized to
      stack with an adjacent helix. The model correctly predicts the effects of
      disrupting this pair in a U1086 sequence variant. Although the set of "tertiary"
      interactions contributes a significant fraction of the RNA unfolding enthalpy
      (delta H approximately 25 kcal/mol, out of 180 kcal/mol total), its overall
      stability is marginal at 37 degrees C.

PMID- 7512653
TI  - Salt effects on ligand-DNA binding. Minor groove binding antibiotics.
AB  - Salt dependent electrostatic effects play a central role in intermolecular
      interactions involving nucleic acids. In this paper, the finite-difference
      solution to the nonlinear Poisson-Boltzmann (NLPB) equation is used to evaluate
      the salt dependent contribution to the electrostatic binding free energy of the
      minor groove binding antibiotics DAPI, Hoechst 33258 and netropsin to DNA using
      detailed molecular structures of the complexes. For each of these systems, a
      treatment based on the NLPB equation accurately describes the variation of the
      experimentally observed binding constant with bulk salt concentration. A
      solvation formalism is developed in which salt effects are described in terms of
      three free energy contributions: the electrostatic ion-molecule interaction free
      energy, delta delta G degrees im; the electrostatic ion-ion interaction free
      energy, delta delta G degrees ii; and the entropic ion organization free energy,
      delta delta G degrees org. The electrostatic terms, delta delta G degrees im and
      delta delta G degrees ii, have both enthalpic and entropic components, while the
      term delta delta G degrees org is purely a cratic entropy. Each of these terms
      depends significantly on salt dependent changes in the counterion and coion
      concentrations around the DNA. In each of the systems studied, univalent ions
      substantially destabilize charged ligand-DNA complexes at physiological salt
      concentrations. This effect involves a salt dependent redistribution of
      counterions near the DNA. The free energy associated with the redistribution of
      counterions upon binding is dominated by the unfavorable change in the
      electrostatic ion-molecule interactions, delta delta G degrees im, rather than
      the change in the cratic entropy of ion organization, delta delta G degrees org.
      In addition, the observed slope of the salt dependence of the free energy is
      determined by electrostatic ion-molecule and ion-ion interactions as well as the
      cratic entropy of ion release. These findings are in contrast to models in which
      the cratic entropy of counterion release drives binding.

PMID- 7512654
TI  - Protection by Cyclosporin A of ischemia/reperfusion-induced damage in isolated
      rat hearts.
AB  - Reperfusion following a period of ischemia can salvage the myocardium only if the
      ischemic episode has not exceeded a certain time limit; beyond this point damage
      becomes irreversible. A key feature of the transition from reversible to
      irreversible injury is mitochondrial dysfunction which may involve the opening of
      a non-specific pore in the mitochondrial inner membrane. Pore opening can be
      induced in vitro by exposure of isolated mitochondria to high [Ca2+] and Pi. Such
      pore formation is sensitized by adenine nucleotide depletion and oxidative stress
      and can be blocked by the immunosuppressant cyclosporin A. Here we show that in
      isolated perfused rat hearts subjected to 30 min ischemia and 15 min reperfusion,
      0.2 microM cyclosporin A restored the ATP/ADP ratio and AMP content (decreased
      and increased respectively during ischemia) to pre-ischemic values. In separate
      experiments functional recovery was assessed by monitoring the restoration of
      left ventricular developed pressure (LVP) during reperfusion after 30, 40 or 45
      min ischemia. LVP was substantially improved in the presence of 0.2 microM
      cyclosporin A but did not return to pre-ischemic levels. The cyclosporin
      analogues G and H were less effective than cyclosporin A in protecting the heart
      during reperfusion. This is consistent with their reduced ability to protect
      isolated mitochondria from damage caused by Ca2+ overload. Surprisingly,
      reperfusion of hearts with 1 microM cyclosporin A reversed the protective effect
      seen at 0.2 microM.

PMID- 7512655
TI  - A positive intracavernous injection test implies normal veno-occlusive but not
      necessarily normal arterial function: a hemodynamic study.
AB  - During impotence evaluations a positive intracavernous injection test has been
      presumed to signify normal erectile hemodynamics. This premise was tested by
      obtaining hemodynamic data in 80 patients 17 to 65 years old with positive
      injection tests: patients achieved maximal circumference responses and
      equilibrium intracavernous pressures of 80 mmHg or more (range 80 to 136)
      sustained for 30 minutes or longer. Corporeal veno-occlusive testing revealed
      that flow-to-maintain (0.5 to 3 ml. per minute) and pressure decay (0 to 47 mmHg)
      values as well as pharmaco-cavernosography findings (absent or minimal contrast
      medium in venous structures in 92% of the cases) were all consistent with low
      outflow erection states. Arterial testing revealed right and/or left cavernous
      systolic arterial blood pressures always at 80 mmHg or more, consistent with a
      prerequisite cavernous artery pressure value for a positive injection test.
      Systemic-cavernous systolic arterial blood pressure gradients were 0 to 24 mmHg,
      25 to 34 mmHg and 35 mmHg or more in 47 (59%), 18 (22%) and 15 (19%) patients,
      respectively. Large systemic-cavernous pressure gradients suggested the presence
      of arterial occlusive disease. In 8 patients with positive injection tests and
      gradients of 35 mmHg or more pharmaco-arteriography revealed hemodynamically
      significant arterial occlusions. In conclusion, hemodynamic data in selected
      patients with positive injection tests revealed low outflow erection states,
      threshold cavernous artery pressures and disparities in systemic-cavernous
      systolic pressure gradients that suggested arterial disease in 19% of the cases.
      The erectile response in a positive test is equal to or greater than a threshold
      response, not always the maximum response as determined by the systemic blood
      pressure. A positive intracavernous injection test did not necessarily signify
      normal erectile hemodynamics.

PMID- 7512656
TI  - Surgical treatment of invasive squamous cell carcinoma of the penis:
      retrospective analysis of 350 cases.
AB  - Between 1960 and 1987, 414 patients with invasive squamous cell carcinoma of the
      penis were referred to the Brazilian National Cancer Institute. Inguinal
      metastases were demonstrated by lymphadenectomy in 39% of the 23 patients with
      stage N0, 49% of 92 with stages N1 and N2, and 100% of 18 with stage N3 disease.
      We analyzed the followup of 350 patients who underwent surgical treatment. In 224
      patients (64%) amputation or some form of penile surgery was done initially,
      while 102 (29%) underwent amputation and lymphadenectomy, and 24 (7%) underwent
      palliative surgery for advanced squamous cell carcinoma. The statistics revealed
      a better 5-year survival rate for the patients who underwent lymphadenectomy
      concomitantly with penile surgery compared to those who underwent delayed
      lymphadenectomy (p < 0.001). Patients in whom systematic lymphadenectomy was
      negative had a better prognosis than those with positive systematic
      lymphadenectomy results (p < 0.001). The latter patients had a better prognosis
      compared with those in whom delayed lymphadenectomy was positive (p = 0.0103).
      Patients with well and moderately differentiated carcinoma had a higher survival
      rate at 5 years than did those with poorly differentiated carcinoma (p < 0.001
      and p = 0.003, respectively). All deaths from metastatic disease occurred within
      24 months among the patients who underwent systematic lymphadenectomy and within
      5 years after simple penile surgery. In the short term, surgical debulking
      combined with reconstruction techniques allowed for improved quality of life in
      patients with advanced local-regional disease.

PMID- 7512657
TI  - Results of an epidemiological survey using a modified American Urological
      Association symptom index for benign prostatic hyperplasia in France.
AB  - The prevalence of urinary symptoms associated with benign prostatic hyperplasia
      was studied in a community-based, nationwide, representative sample of 2,011
      French men 50 to 80 years old. Symptoms were assessed by the American Urological
      Association symptom index. After exclusion of patients with prostate cancer, 6.9%
      of the subjects reported having undergone prostate surgery. Among the surgery
      free subjects, nocturia and repeat voiding within 2 hours were the most prevalent
      symptoms. Based on the American Urological Association symptom index, 18.8% of
      the men were considered free of urinary symptoms, and 67%, 13% and 1.2%,
      respectively, ranked between 1 and 7, 8 and 19, and 20 or more. The proportion of
      men scoring greater than 7 approximately doubled with each decade of age. Our
      estimation indicated that in 1992 approximately 1.14 million French men had
      moderate to severe urinary symptoms that were likely to be associated with benign
      prostatic hyperplasia. Previous studies had yielded higher prevalence estimates,
      probably due to differences in sampling design and diagnostic criteria.

PMID- 7512658
TI  - High intensity focused ultrasound for the treatment of benign prostatic
      hyperplasia: early United States clinical experience.
AB  - High intensity focused ultrasound via a transrectal approach was used to treat 15
      patients with symptomatic benign prostatic hyperplasia. The first 10 of these 15
      patients underwent continuous temperature monitoring of the periprostatic region
      throughout the treatment. Patients undergoing transperineal thermocouple
      placement for the purpose of thermometry were treated while under general or
      spinal anesthesia, whereas 4 of the 5 remaining patients were successfully
      treated using intravenous sedation alone. Of the 10 patients 9 did not
      demonstrate a significant temperature elevation. One patient with a small
      prostatic anteroposterior diameter had a transient elevation of 17C. No patient
      experienced a complication related to periprostatic heating. Followup was
      available at 90 days in all patients. At 90 days the symptom scores decreased
      from a pretreatment value (American Urological Association questions 1 to 7) of
      31.2 (range 22 to 38) to 15.8 (range 8 to 31). Peak flow rate increased by a mean
      of 4.7 ml per second from 9.3 ml per second before treatment to 14.0 ml per
      second at 90 days. The most frequent complication was that of transient urinary
      retention in 11 of 15 patients (73.3%) and hematospermia in 7 (46.7%). No adverse
      reactions persisted at 90 days. This study represents an initial attempt using
      high intensity focused ultrasound to treat symptomatic benign prostatic
      hyperplasia. Overall, the safety and effectiveness of high intensity focused
      ultrasound demonstrated in this pilot study are encouraging.

PMID- 7512660
TI  - Prostate specific antigen cannot distinguish stage T1a (A1) prostate cancer from
      benign prostatic hyperplasia.
AB  - To determine if serum prostate specific antigen (PSA) has decreased the
      prevalence of stages T1a (A1) and T1b (A2) prostate cancer, and to compare the
      PSA values for patients with stages T1a and T1b prostate cancer and men with
      symptomatic benign prostatic hyperplasia, 966 patients undergoing transurethral
      resection of the prostate were evaluated retrospectively. Included in the study
      population were 499 consecutive patients who underwent transurethral resection of
      the prostate for obstructive urinary symptoms in 1986 (no PSA group), and 467
      consecutive patients who underwent resection in 1989 and 1990 who were evaluated
      with serum PSA preoperatively (PSA group). The mean age for the no PSA group was
      71 years compared to 70 years for the PSA group (p = 0.36). The overall
      prevalence of stages T1a and T1b prostate cancer in the no PSA group was 8.6%
      compared to 10.3% in the PSA group (p = 0.37). The prevalence of stages T1a and
      T1b prostate cancer in the no PSA group was 3.6% and 5.0%, respectively, compared
      to 7.3% and 3.0%, respectively, for the PSA group (p = 0.01). In the PSA group
      the median PSA value for patients with stages T1a and T1b prostate cancer was 3.8
      ng/ml compared to 3.4 ng/ml for the patients without cancer (p = 0.59). The
      median PSA level for the stage T1a cancer patients was 2.4 ng/ml, which was not
      statistically different from that in patients without cancer (p = 0.31), and the
      median PSA level for the stage T1b cancer patients was 5.9 ng/ml, which was
      statistically different than that in patients without cancer (p = 0.01). These
      findings suggest that the routine use of serum PSA does not decrease the
      prevalence of stage T1a prostate cancer and that PSA may decrease the prevalence
      of stage T1b tumors but a larger study would be necessary to document this
      finding.

PMID- 7512659
TI  - Comparison of digital rectal examination and serum prostate specific antigen in
      the early detection of prostate cancer: results of a multicenter clinical trial
      of 6,630 men.
AB  - To compare the efficacy of digital rectal examination and serum prostate specific
      antigen (PSA) in the early detection of prostate cancer, we conducted a
      prospective clinical trial at 6 university centers of 6,630 male volunteers 50
      years old or older who underwent PSA determination (Hybritech Tandem-E or Tandem
      R assays) and digital rectal examination. Quadrant biopsies were performed if the
      PSA level was greater than 4 micrograms/l or digital rectal examination was
      suspicious, even if transrectal ultrasonography revealed no areas suspicious for
      cancer. The results showed that 15% of the men had a PSA level of greater than 4
      micrograms/l, 15% had a suspicious digital rectal examination and 26% had
      suspicious findings on either or both tests. Of 1,167 biopsies performed cancer
      was detected in 264. PSA detected significantly more tumors (82%, 216 of 264
      cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer
      detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for
      the 2 methods combined. Positive predictive value was 32% for PSA and 21% for
      digital rectal examination. Of 160 patients who underwent radical prostatectomy
      and pathological staging 114 (71%) had organ confined cancer: PSA detected 85
      (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2
      methods in combination increased detection of organ confined disease by 78% (50
      of 64 cases) over digital rectal examination alone. If the performance of a
      biopsy would have required suspicious transrectal ultrasonography findings,
      nearly 40% of the tumors would have been missed. We conclude that the use of PSA
      in conjunction with digital rectal examination enhances early prostate cancer
      detection. Prostatic biopsy should be considered if either the PSA level is
      greater than 4 micrograms/l or digital rectal examination is suspicious for
      cancer, even in the absence of abnormal transrectal ultrasonography findings.

PMID- 7512661
TI  - Clinical experience of the detection of prostate cancer in patients with benign
      prostate hyperplasia treated with finasteride. The Finasteride Study Group.
AB  - The clinical experience relating to the detection of prostate cancer in patients
      participating in 2 large multicenter clinical trials of finasteride in the
      treatment of benign prostatic hyperplasia is reviewed. A total of 1,645 patients
      40 to 83 years old with benign prostatic hyperplasia was randomized to receive 1
      or 5 mg finasteride or placebo once a day for 12 months in a double-blind fashion
      followed by an open extension study in which all patients were treated with 5 mg
      finasteride daily. At entry, all patients were to have a maximum urinary flow
      rate of 15 ml per second or less with a voided volume of 150 ml or more, an
      enlarged prostate and symptoms of urinary obstruction. Patients with a prostate
      specific antigen level of 40 ng/ml or more, or any finding suggestive of prostate
      cancer were excluded. During the study period 32 cases of prostate cancer were
      diagnosed: 12 were detected during the 12 months of the controlled study and were
      evenly distributed among the treatment groups (4 on placebo, and 3 on 1 mg and 5
      on 5 mg finasteride) and 20 cases were detected in the extension study. From
      these results we conclude that finasteride-treated patients should be evaluated
      periodically by digital rectal examination, careful monitoring of prostate
      specific antigen levels and appropriate investigation of any suspicious findings.

PMID- 7512662
TI  - Eliminating the need for bilateral pelvic lymphadenectomy in select patients with
      prostate cancer.
AB  - To determine if the preoperative variables of serum prostate specific antigen
      (PSA), primary Gleason grade from the biopsy specimen and local clinical stage as
      determined from digital rectal examination can accurately predict the pelvic
      lymph node status in patients with clinically localized prostate cancer, we
      reviewed the medical records of 1,632 patients who underwent bilateral pelvic
      lymphadenectomy at our institution between January 1988 and December 1991. Using
      logistic regression analysis, serum PSA was found to be the best predictor of
      pelvic lymph node metastases (p < 0.0001). The predictive power of serum PSA
      could be enhanced considerably by taking into account the Gleason grade (p <
      0.001) and local clinical stage (p < 0.001). A statistical model using all 3
      variables was developed that allows the practicing urologist to estimate on an
      individual basis the probability of pelvic lymph node involvement. Using a
      conservative cutoff point of less than 3% as an acceptable false-negative rate,
      61% of the patients with clinical stages T1a to T2b (A1 to B1) disease and 29% of
      those with clinical stages T1a to T2c (A1 to B2) prostate cancer may be spared an
      open or laparoscopic staging bilateral pelvic lymphadenectomy. As a result,
      patient morbidity can be decreased and a significant economic savings to the
      health care system can be realized. This observation has particular importance
      for prostate cancer patients being managed with radical perineal prostatectomy or
      definitive radiation therapy.

PMID- 7512664
TI  - The development of detrusor instability in prostatic obstruction in relation to
      sequential changes in voiding dynamics.
AB  - We studied 34 patients with benign prostatic hypertrophy who had infravesical
      obstruction with a high opening pressure and a stable bladder. No treatment was
      given except for intermittent short courses of plant extracts. There were no
      factors other than prostatic obstruction that could affect the mechanics of
      micturition. The patients were reassessed after a mean of 21 months (range 7 to
      62). Voiding dynamics were unchanged in 12 patients who had a stable obstructed
      bladder, while 22 had an unstable obstructed bladder with a significantly greater
      opening pressure. Peak flow pressure was also increased but much less so that at
      the onset of voiding. The driving pressure and bladder volume were decreased.
      Despite this fact, urine flow rates were unchanged and maximum external voiding
      power was enhanced. The significance of such findings is discussed.

PMID- 7512663
TI  - Early androgen ablation for stage D1 (N1 to N3, M0) prostate cancer: prognostic
      variables and outcome.
AB  - To elucidate the outcome for patients with stage D1 (N1 to N3, M0) prostate
      cancer we reviewed 179 patients with lymphadenectomy proved pelvic nodal
      metastases who underwent immediate androgen ablation as the only initial
      treatment. With a median followup of 43 months, the 5 and 8-year actuarial rates
      of freedom from disease progression were 55% and 25%, respectively, and the
      median interval to disease progression was 67 months. The 5 and 8-year survival
      rates were 85% and 57%, respectively. Median survival after disease progression
      was 36 months. Local and distant disease progression was equally important. At 5
      and 8 years the incidence of local progression was 32% and 51%, respectively,
      while metastatic rates at the same intervals wer 22% and 44%, respectively.
      Multivariate regression revealed that tumor grade and transurethral resection in
      preoperative stage C disease correlated with disease progression. Pretreatment
      prostate specific antigen (PSA) levels were not predictive of outcome. The fact
      that transurethral resection predicted for local as well as distant failure
      suggests that the procedure selects for rather than aggravates adverse disease.
      Posttreatment PSA levels were a sensitive index of response to treatment and of
      subsequent outcome. All patients who failed to achieve undetectable PSA levels
      had relapse by 8 years, whereas those whose levels became undetectable
      experienced only a 5% incidence of disease progression. These data show that
      androgen ablation alone is not curative for node positive disease but is
      associated with significant disease control and good short-term (5-year)
      survival. The primary tumor is an important source of androgen insensitive cells
      and comprehensive treatment strategies for this stage of disease require
      attention to the primary tumor as well as microscopic metastases.

PMID- 7512665
TI  - Re: A prospective, placebo-controlled study of the antiandrogen Casodex as
      treatment for patients with benign prostatic hyperplasia.

PMID- 7512666
TI  - Re: The inability of prostate specific antigen index to enhance the predictive
      value of prostate specific antigen in the diagnosis of prostatic carcinoma.

PMID- 7512669
TI  - [Mutational analysis of platelet fibrinogen receptor ligand binding domain].
AB  - Platelet glycoprotein (GP) IIb-IIIa (alpha IIb beta 3) binds fibrinogen with high
      affinity. To identify structure responsible for the alpha IIb beta 3 specific
      fibrinogen binding, chimeric receptors between alpha IIb and alpha v were
      constructed, expressed on heterologous cells, and their function was analyzed.
      Chimeric receptors with mutations in calcium binding sequences showed similar
      ligand specificity as wild type receptor. However, those with replacements in
      amino-terminal regions revealed substitutions of the epitopes for specific
      receptor-blocking antibodies, indicating importance of this amino-terminal region
      for alpha IIb beta 3 specific ligand recognition.

PMID- 7512667
TI  - Interleukin 6 receptor mRNA in prostate carcinomas and benign prostate
      hyperplasia.
AB  - We investigated the presence of interleukin 6 (IL6) receptors in human prostate
      carcinomas and benign prostatic hyperplasias. Interleukin 6 receptor expression
      was measured at the mRNA level by slot blot analysis using a probe that
      recognizes mRNA encoding the 80-kDa subunit of the IL6 receptor. Significant
      expression was found in 29 of 37 (78%) samples of benign prostate hyperplasia
      (BPH) and in 17 of 17 prostate carcinomas. Quantitative analysis of the
      expression level revealed that 11 of the 29 positive hyperplasia tissues (38%)
      and 4 carcinoma samples (23.5%) expressed equal or higher levels of IL6 receptor
      mRNA than the human hepatoma cell line PLC/PRF5, which contains about 2300 IL6
      receptors per cell. We also measured IL6 receptor mRNA levels in three human
      prostate carcinoma cell lines LNCaP, DU145 and PC3, which are known to contain
      IL6 receptors because they are sensitive to the cytotoxic action of an IL6-toxin
      fusion protein. We were not able to detect IL6 receptor expression with the slot
      blot procedure, but we were able to detect IL6 receptor mRNA using a very
      sensitive PCR assay. Our data provide evidence that IL6 may play a role in the
      growth of benign and malignant prostate tumors and suggest that the IL6 receptor
      could be a target for the delivery of therapeutic agents in prostate cancer.

PMID- 7512668
TI  - [Structure and function of L-selectin].
AB  - L-selectin, one of the selectin (LECAM) members, is thought to be the lymphocyte
      homing receptor that mediates binding of lymphocytes to high endothelial venules
      of peripheral lymph nodes. Although L-selectin is probably the most well
      characterized lymphocyte adhesion molecule, there are still a number of
      unresolved issues, one of which is exact operating mechanism in the lymphocyte-HE
      cell interaction. This molecule is expressed not only by lymphocytes but also by
      all other types of leukocytes which in fact never recirculate in the body. We
      have cloned cDNA encoding rat L-selectin and produced a soluble fusion protein of
      rat L-selectin and human IgG, and used it to identify ligand structures
      recognized by L-selectin, and also to produce blocking as well as non-blocking
      monoclonal antibodies to rat L-selectin. By using these tools, we investigated
      the biological significance of interaction between L-selectin and its ligand.
      Summary of these results are presented herein.

PMID- 7512671
TI  - [Problems in the diagnosis of acute pancreatitis].

PMID- 7512672
TI  - Renal cell carcinoma producing alpha-fetoprotein (AFP) with a unique lectins
      affinity profile.
AB  - Renal cell carcinoma (RCC) producing alpha-fetoprotein (AFP) is a rare entity and
      merely 7 cases have been reported so far. The present case, a 71-year-old woman,
      showed a high serum AFP level of 204 ng/ml. The RCC of the autopsied right kidney
      consisted mainly of spindle-shaped or bizarre sarcomatous tumor cells. AFP was
      immunolocalized only in the concomitant clear cell component. Concanavalin A (Con
      A)-nonadsorption rate of serum AFP was 42%, which was an intermediate value
      between those of yolk sac tumors and metastatic liver carcinomas. Lens culinalis
      agglutinin (LCA)-affinity study of the patient's AFP showed an unknown peak X,
      which was eluted between the known peaks 2 and 3. These results suggest a certain
      structural alteration in carbohydrate moieties of the AFP derived from this RCC.
      A review of the clinicopathologic features of 8 patients with AFP-producing RCC
      was made to understand the pathophysiology of AFP-producing neoplasms.

PMID- 7512673
TI  - Influence of portal branch ligation on the outcome of repeat dearterializations
      of an experimental liver tumor in the rat.
AB  - It has been suggested that the portal vein should be occluded during intermittent
      hepatic dearterialization in order to induce a more complete ischemia of the
      tumor. In this experiment the influence of portal branch ligation in combination
      with repeat dearterializations on a liver tumor was investigated. Twenty-seven
      rats were randomly allocated to sham treatment (n = 6); portal branch ligation
      (PBL) (n = 7); 120 min of repeat dearterialization (n = 7); and portal branch
      ligation (PBL) in combination with 50 min of repeat dearterialization (n = 7)
      (once a day during 5 days). The results showed that portal branch ligation alone
      did not alter the tumor growth compared with sham treatment (P > 0.05), nor did
      portal branch ligation in combination with repeat dearterializations for 50 min
      (P > 0.05). However, tumor growth delay was achieved following 120 min of repeat
      dearterializations without occlusion of the portal branch (P < 0.01 versus all
      the other groups). There was a significant weight loss of the lobe undergoing
      PBL, whether dearterialization was added or not (P < 0.001). The liver
      nucleotide/DNA and RNA/DNA ratio significantly decreased as well. Histological
      examination showed that > 50% of tumor cells became necrotic after repeat
      dearterializations for 2 hr indicating a significant damage to tumor tissue. In
      contrast, PBL in combination with repeat dearterializations for 50 min induced
      extensive liver necrosis without having any influence on tumor growth.

PMID- 7512670
TI  - Immunohistochemical localization of acidic and basic fibroblast growth factors in
      human benign and malignant thyroid lesions.
AB  - The localization of acidic fibroblast growth factor (aFGF) and basic fibroblast
      growth factor (bFGF) was investigated immunohistochemically in human benign and
      malignant thyroid lesions. Immunostaining for aFGF and bFGF displayed diffuse or
      granular deposits of the reaction products in the cytoplasm of neoplastic cells,
      especially in the marginal region of follicular adenoma, follicular carcinoma and
      papillary carcinoma. All lesions except for diffuse hyperplasia, which was
      completely negative in immunostaining for all antibodies, showed an increased
      immunostaining for bFGF (Ab-1) over that of aFGF and bFGF (Ab-2). Basement
      membranes of follicular and papillary structure and the fibroblasts located in
      the stromal tissues were free from immunostaining for all antibodies. The ratio
      of positive immunostaining for all antibodies was highest in papillary carcinoma,
      with an incidence of more than 80.0%, followed, in descending order, by widely
      invasive follicular carcinoma, minimally invasive follicular carcinoma,
      follicular adenoma and normal thyroid, in which some follicular cells exhibited
      weak reaction products. aFGF with a molecular weight of 18 kDa was identified in
      papillary carcinoma of the thyroid. From these data, we concluded that aFGF is
      synthesized in the neoplastic follicular cells of the thyroid, and aFGF and bFGF
      may have important roles in the neoplastic proliferation of follicular cells.

PMID- 7512675
TI  - Alpha-fetoprotein-producing rectal cancer: calculated tumor marker doubling time.
AB  - alpha-fetoprotein (AFP) production by rectal cancer is very rare. In the English
      literature there are only a few reported cases in which serum AFP level was >
      1,000 ng/ml. A 43-year-old Japanese man with rectal cancer and liver metastases
      had a high serum AFP level (941 ng/ml) when first evaluated. Three weeks later,
      the serum AFP level was extremely elevated (7,060 ng/ml). He underwent
      abdominoperineal excision of the rectum and biopsy of liver metastases. The
      placement of an intrahepatic-arterial infusion catheter into the proper hepatic
      artery via the right gastroepiploic artery was also performed.
      Immunohistochemically, AFP-positive cells were identified in both the rectal and
      liver tumors. Nine days postoperatively, the serum AFP level was 2,000 ng/ml. In
      spite of intensive chemoimmunotherapy, serum AFP level was increased and 14 weeks
      after surgery was extremely elevated (267,300 ng/ml). The patient succumbed to
      cancer 3 months after surgery. To our knowledge, this is the first case of an AFP
      producing rectal cancer in which AFP doubling time could be calculated as 12.8
      days.

PMID- 7512674
TI  - Endometrioid adenocarcinoma of the prostate: a clinicopathologic and
      immunohistochemical study.
AB  - On retrospective review of the tumor registry files between 1979 and 1992 at the
      North Iowa Medical Center, six cases of endometrioid adenocarcinoma of the
      prostate were identified among 1582 cases of prostatic carcinoma. Along with long
      term clinicopathologic follow-up, immunohistochemical studies of the prostatic
      tumor tissues were performed. All six cases of endometrioid carcinoma, together
      with control cases of benign prostatic hypertrophy (BPH) and ordinary
      adenocarcinoma of the prostate had unequivocal diffuse positive staining for PSA
      and similar reactivity to ER-D5 and PS2. Thus, endometrioid carcinoma is most
      likely derived from the prostate or prostatic urethral duct rather than the
      utricle. However, due to its unusual initial clinical manifestations, biological
      behavior, and distinctive histomorphology, the term "endometrioid adenocarcinoma
      of the prostate" is worth preserving.

PMID- 7512676
TI  - The quaternary structures of untransformed steroid hormone receptors: an open
      issue.
AB  - Oligomeric forms of steroid hormone receptors have been observed since the
      original detection of these proteins in cytosols from target tissues, and the
      capacity of receptors to arrange in supramolecular entities was found to be
      related to their functional untransformed states of low affinity for nuclear
      acceptor sites. In this paper we discuss the models of quaternary structures of
      untransformed receptors and steroid-receptor complexes proposed in the last two
      decades, including homo-oligomers as well as hetero-oligomers containing non
      steroid binding proteins and/or RNA. The multiplicity of forms detected in cell
      free systems, their stabilization by unphysiological experimental conditions, and
      their sensitivity to the ionic species employed to prepare and analyze steroid
      receptors, are critically evaluated, and it is concluded that the extrapolation
      of models to account for quaternary structure of receptors in intact cells is
      unwarranted. We have also discussed the experimental strategies which have been
      developed to circumvent the possible artefactual changes in the arrangements of
      oligomeric receptors following cell rupture, in order to probe the existence of
      these forms in vivo, and to characterize their composition and structure. The
      data obtained by these studies support the concept that oligomeric untransformed
      steroid receptors exist in intact cells, where they can be present in multiple
      supramolecular arrangements whose quaternary structures remain to be established.

PMID- 7512677
TI  - Anatomic subtype and survival after reconstructive operation for hypoplastic left
      heart syndrome.
AB  - We conducted a retrospective study of 78 patients who underwent palliative
      reconstructive operation for hypoplastic left heart syndrome representing an
      entire consecutive experience between 1983 and 1991 to identify predictors of
      mortality that might enable more appropriate triage of patients to either
      reconstruction or transplantation. Twenty-nine patients had aortic atresia,
      mitral atresia; 18 had aortic stenosis, mitral stenosis; 20 had aortic atresia
      and mitral stenosis; and 11 had miscellaneous forms of hypoplastic left heart
      syndrome. There were 29 hospital deaths (37%). A worst preoperative pH (p = 0.01)
      and immediate preoperative pH (p = 0.03) less than the median were predictors of
      hospital mortality. The anatomic subgroup aortic atresia, mitral stenosis (p =
      0.06) had a possible increased hospital mortality. One patient was lost to follow
      up. The Kaplan-Meier survival estimate among hospital survivors was 34% at 3
      years and 25% at 5 years. The anatomic subgroup aortic atresia, mitral atresia (p
      = 0.02) had a worse late outcome (11% 3-year survival) whereas the subgroup
      aortic stenosis, mitral stenosis (p = 0.04; 76% 3-year survival) had a better
      late outcome. There were no other significant predictors of late survival other
      than immediate prerepair pH (p = 0.05). Interpretation of this experience is
      complicated by the large number of different surgical techniques used for both
      first-stage neonatal reconstruction and the Fontan procedure plus introduction of
      the bidirectional Glenn shunt as an intermediate step midway through the
      experience. Nevertheless in this time frame and with the variety of techniques
      used, this experience demonstrates that patients with aortic atresia, mitral
      atresia, particularly those who have been very acidotic in the neonatal period,
      are least likely to do well with the reconstructive approach to hypoplastic left
      heart syndrome and are the most appropriate subgroup to be directed to
      transplantation. Patients with aortic stenosis, mitral stenosis have an excellent
      late outcome with the reconstructive approach.

PMID- 7512678
TI  - Risk factors for graft failure associated with pulmonary hypertension after
      pediatric heart transplantation.
AB  - Postoperative pulmonary hypertension can be a major cause of early death after
      heart transplantation in children. To identify predictive risk factors of
      pulmonary hypertension after heart transplantation, we performed a retrospective
      analysis of our 194 infant and pediatric recipients who underwent heart
      transplantation between 1987 and 1992. Because the response of pulmonary
      vasculature may change during growth, the patients were divided into two groups:
      age less than 1 year in group I (n = 152) and 1 year or older in group C (n =
      43). The following risk factors were evaluated: cardiomyopathy, congenital heart
      disease and hypoplastic left heart syndrome, pretransplant pulmonary
      hypertension, history of operation, oversized donor (donor/recipient weight ratio
      greater than 2), donor's history of cardiopulmonary resuscitation, and prolonged
      graft ischemic time (graft ischemic time 360 minutes or longer). Though there was
      no significant difference between group I and group C in overall early mortality
      including early graft loss (19 of 152 versus 5 of 42), the mortality rate from
      pulmonary hypertension in group I was significantly lower than that in group C (2
      of 152 versus 4 of 42; p < 0.05). The mortality rate from pulmonary hypertension
      in patients with congenital heart disease in group I was significantly lower than
      that in group C (0 of 44 versus 4 of 24; p < 0.05). In group I, there was no
      significant difference in the early mortality rate or the mortality rate from
      pulmonary hypertension from any factors studied. The mortality rate from
      pulmonary hypertension in association with prolonged graft ischemic time in group
      C was significantly higher than when no prolonged graft ischemic time was present
      in group C and with either prolonged graft ischemic time or no prolonged graft
      ischemic time in group I (4 of 16 versus 0 of 26, 0 of 37, and 2 of 115). In
      conclusion, older patients had a higher mortality rate from pulmonary
      hypertension after heart transplantation, especially in patients with congenital
      heart disease who received a graft preserved more than 6 hours. This study
      demonstrates another benefit of early heart transplantation in infancy, that is,
      prevention of death from pulmonary hypertension.

PMID- 7512679
TI  - Incidence and clinical importance of perioperative histamine release: randomised
      study of volume loading and antihistamines after induction of anaesthesia. Trial
      Group Mainz/Marburg.
AB  - Although histamine release is recognised as a common event during anaesthesia and
      surgery, few clinicians judge the resultant cardiorespiratory disturbances
      serious enough to warrant prophylaxis with antihistamines. We have assessed the
      incidence and importance of histamine release in a randomised 2 x 2 factorial
      study. 240 patients representing a routine throughput of major general surgery
      were studied during a standardised induction of anaesthesia and preoperative
      loading of the circulation with either Ringer solution or Haemaccel-35, with or
      without antihistamine prophylaxis with dimetindene (H1) plus cimetidine (H2).
      Cardiorespiratory disturbances were graded as detectable, clinically relevant, or
      life-threatening from observers' records of the anaesthesia and the actions taken
      by the anaesthetists. Disturbances that were accompanied by significant rises in
      plasma histamine were further designated histamine-related, and those that were
      not were designated histamine-unrelated. Anaesthetists, observers, and
      designators were blinded to whether or not the patients had received
      antihistamines and to which solution was used for circulatory volume loading.
      Clinically relevant or life-threatening histamine-related disturbances occurred
      in 8% of the patients who after induction of anaesthesia received Ringer without
      antihistamines, in 26% of those who received Haemaccel without antihistamines,
      and in 2% or less of those who received antihistamines (p < or = 0.0001). There
      were 4 life-threatening histamine-related disturbances, all in patients who
      received Haemaccel without antihistamines (p < 0.01). Histamine-unrelated
      disturbances occurred in 16% overall, with no obvious effect of Haemaccel or
      antihistamines. The histamine-related disturbances under anaesthesia were
      remarkable for their severity (even with small rises in histamine
      concentrations), for the prevalence of bradycardia, and for the absence of skin
      signs. Their likelihood and severity were increased in patients with tumours. The
      results of the trial make a case for routine prophylaxis with antihistamines as
      part of anaesthetic management.

PMID- 7512680
TI  - Ethics of a prostate cancer screening trial.

PMID- 7512682
TI  - Lindane exposure and aplastic anaemia.

PMID- 7512681
TI  - Diagnosis of growth-hormone deficiency in adults.
AB  - There is no consensus as to the most appropriate method of diagnosing growth
      hormone (GH) deficiency in adults. We have evaluated the relative diagnostic
      merits of measuring peak GH response to insulin-induced hypoglycaemia (insulin
      tolerance test), mean 24 h GH concentration derived from 20 min sampling, serum
      insulin-like growth factor I (IGF-I) concentrations, and serum IGF binding
      protein 3 (IGFBP-3) concentrations. These tests were undertaken in 23 patients
      considered GH deficient from extensive organic pituitary disease, and in 35 sex
      matched normal subjects of similar age and body-mass index. Hypopituitary
      subjects had significantly lower stimulated peak GH, mean 24 h GH, IGF-I, and
      IGFBP-3 concentrations than normal subjects. The ranges of stimulated peak GH
      responses were clearly separated between the hypopituitary (< 0.2-3.1 ng/mL) and
      normal (5.3-42.5 ng/mL) groups, but mean 24 h GH, IGF-I, and IGFBP-3
      concentrations overlapped. Mean 24 h GH concentrations were below assay
      sensitivity in 80% of hypopituitary subjects and 16% of normal subjects. 70% and
      72%, respectively, of the IGF-I and IGFBP-3 values in hypopituitary subjects were
      within the range for normal subjects. We conclude that GH deficiency in adults is
      most reliably identified by stimulatory testing, and that IGF-I and IGFBP-3 are
      poor diagnostic tests of adult GH deficiency.

PMID- 7512683
TI  - Characterization of the protein moiety of U7 small nuclear RNP particles.
AB  - U7 snRNP particles contain a set of seven proteins with molecular weights in the
      range of 13.5 to 50 kD. One protein with a molecular weight of 18 kD carried the
      antigenic determinant responsible for the interaction of U7 snRNPs with
      autoantibodies from patients with connective tissue diseases. It is suggested
      that U7 RNA is associated with proteins representing a ribonucleoprotein particle
      analogous to U1, U2, U4, U5 and U6 snRNPs.

PMID- 7512684
TI  - Increases in chromosome aberrations and in abnormal sperm morphology in rubber
      factory workers.
AB  - Subjects working at a rubber plant in a chemicals warehouse or in calandering and
      bambury units were analyzed for both sperm parameters and structural chromosome
      aberrations in peripheral blood lymphocytes. Sperm analysis was performed in a
      group of 24 workers for comparison with fertile (n = 24) and infertile (n = 24)
      control groups. The statistical analyses of semen volume, vitality and sperm
      count did not show significant differences between exposed and fertile groups but
      significant differences were found from the infertile group. A significantly
      lower proportion of normal sperm head shapes was found in exposed subjects when
      compared to the fertile group (40.1 vs. 57.8). Seven exposed workers were re
      analyzed 1 year later and their sperm parameters did not change. The cytogenetic
      analysis showed a significant increase (3.90%) in the percentage of cells with
      aberrations in bambury workers (n = 11). However, no differences were found
      between calandering workers (n = 8) and control subjects (n = 10). Workplace air
      samples taken on the day of tissue sampling did not show any increase above the
      Cuban maximal allowed concentration for benzo[a]pyrene or toluene.

PMID- 7512685
TI  - Defective splicing induced by 4NQO in the hamster hprt gene.
AB  - The molecular analysis of mutations affecting mRNA processing may contribute to a
      better understanding of the splicing mechanism through the identification of
      genomic sequences necessary for the recognition of splice sites. In this paper we
      report the sequence analysis of 14 splice mutants induced by 4-nitroquinoline 1
      oxide (4NQO) at the hamster hypoxanthine-guanine-phosphoribosyltransferase (hprt)
      locus. We show that mutations at the 3' acceptor splice site or at the first or
      fifth base of the 5' donor splice site are responsible for exon skipping. In
      addition, mutations in exon sequences also determine the skipping of one or more
      exons. Our data indicate that point mutations in intron regions at either side of
      an internal exon may induce the skipping of the same exon, supporting a model
      where the exon is the unit of early spliceosome assembly. Furthermore, they
      suggest that the splicing of hprt mRNA precursors may proceed through a
      clustering of exons 2, 3 and 4 which are then spliced in a concerted way.

PMID- 7512686
TI  - Antimutagenicity in Euglena gracilis.
AB  - The genotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and
      furadantine (Fu) was significantly decreased by standard antimutagens (ascorbic
      acid, alpha-tocopherol, chlorophyllin and sodium selenite) in the unicellular
      flagellate Euglena gracilis. The effects of these compounds were verified also by
      a bacterial test in which three strains of Salmonella typhimurium, TA97, TA100,
      and TA102, were used. The above compounds were antimutagenic in strains of
      bacteria used, except for chlorophyllin which had no effect on strain TA102.

PMID- 7512687
TI  - Nucleotide sequence between recA and alaSp in E. coli K12 and the sequence change
      in four recA mutations.
AB  - The sequence of 366 nucleotides between the C-terminal trailer region of recA and
      the N-terminal leader region of alaS is presented. This sequence reveals an open
      reading frame of 166 codons we have named oraA. An NdeI restriction nuclease
      cleavage site also revealed by the sequence was used to clone, map and sequence
      three recA mutations: recA11, recA12 and recA52. A mutation in recA (recA946),
      was discovered in strains originally reported to contain recH166. The relation
      between recA946 and recH166 is unclear.

PMID- 7512688
TI  - Repair in ribosomal RNA genes is deficient in xeroderma pigmentosum group C and
      in Cockayne's syndrome cells.
AB  - Previous studies have demonstrated transcription-coupled DNA repair in mammalian
      genes transcribed by RNA polymerase II but not in ribosomal RNA genes (rDNA),
      which are transcribed by RNA polymerase I. The removal of UV-induced cyclobutane
      pyrimidine dimers (CPD) from rDNA in repair-proficient human cells has been shown
      to be slow but detectable and apparently not coupled to transcription. We studied
      the induction and removal of CPD from rDNA in cultured cells from two repair
      deficient human disorders. Primary xeroderma pigmentosum complementation group C
      (XP-C) cells, whether proliferating or nondividing, removed no CPD from either
      rDNA strand in 24 h post-UV, a result which supports earlier conclusions that XP
      C cells lack the general, transcription-independent pathway of nucleotide
      excision repair. We also observed lower than normal repair of rDNA in Cockayne's
      syndrome (CS) cells from complementation groups A and B. In agreement with
      previous findings, the repair of both strands of the RNA polymerase II
      transcribed dihydrofolate reductase gene was also deficient relative to that of
      normal cells. This strongly suggests that the defect in CS cells is not limited
      to a deficiency in a transcription-repair coupling factor. Rather, the defect may
      interfere with the ability of repair proteins to gain access to all expressed
      genes.

PMID- 7512689
TI  - The induction of Robertsonian translocations by X-rays and mitomycin C in mouse
      cells.
AB  - The induction of Robertsonian translocations in murine C3H 10T1/2 embryo
      fibroblasts after exposure to X-rays and mitomycin C has been investigated. Cells
      were irradiated in log-phase and harvested at different times for chromosome
      analysis. The stage of the cell cycle of individual cells at the time of
      irradiation could be determined by differential replication staining. A dose
      dependent delay in the progression through S- and G2-phase has been observed. X
      rays produced an increase in the frequency of Robertsonian translocations when
      cells were exposed in G1- or S-phase, but not in G2. The dose-response curve for
      the induction of Robertsonian translocations both in G1 and S peaked at 2 Gy and
      slightly declined at higher doses. For G2 cells, an increase compared to the
      control level was observed only after 1 Gy. Mitomycin C induced chromosomal
      aberrations and Robertsonian translocations in 10T1/2 cells, but no significant
      interaction between ionizing radiation and the alkylating agent was observed for
      these two endpoints. However, the combined exposure caused satellite associations
      of chromosomes. Both the number of satellite associations/metaphase (five times
      the frequency observed after mitomycin C alone) and the number of
      chromosomes/satellite (up to 10 chromosomes were observed in satellite
      associations) were greatly enhanced compared to X-rays and mitomycin C alone.

PMID- 7512690
TI  - Induction of chromosome aberrations by pyrimethamine in cultured Chinese hamster
      (CHL) cells.
AB  - Induction of chromosome aberrations was investigated in cultured Chinese hamster
      cells treated with pyrimethamine. Pyrimethamine without metabolic activation
      strongly induced structural chromosome aberrations in a dose-dependent manner.
      Aberrant metaphase cells occurred at a frequency of 80%, when cells were treated
      at 1.6 microgram/ml for 48 h.

PMID- 7512691
TI  - Sensorimotor neuropathy resembling CIDP in patients receiving FK506.
AB  - FK506 is an important immunosuppressant that has shown great promise in the
      treatment of autoimmune diseases. Approximately 5% of patients receiving FK506
      develop major central nervous system toxicity, but the peripheral nerves are
      usually spared. During 1990-1991, some 1000 patients received liver transplants
      under FK506 immunosuppression. Of these, 3 patients developed severe multifocal
      demyelinating sensorimotor polyneuropathy 2-10 weeks after initiation of FK506
      therapy. Improvement followed plasmapheresis or intravenous immunoglobulin
      (IVIG), suggesting an immune-mediated cause. Although autoimmune neuropathy has
      been previously reported in immune-deficient states such as Hodgkin's disease and
      AIDS, it is not an expected complication of immunosuppressive therapy. However,
      others have shown that this phenomenon can be produced in rats with cyclosporine
      A (CsA), whose effects on T-cell subsets are similar to those seen with FK506.
      These T-cell subset changes may have precipitated this dysimmune neuropathy in
      our patients.

PMID- 7512692
TI  - Nitric oxide directly activates calcium-dependent potassium channels in vascular
      smooth muscle.
AB  - Nitric oxide is the major endothelium-derived relaxing factor (EDRF), and it is
      thought to relax smooth muscle cells by stimulation of guanylate cyclase,
      accumulation of its product cyclic GMP, and cGMP-dependent modification of
      several intracellular processes, including activation of potassium channels
      through cGMP-dependent protein kinase. Here we present evidence that both
      exogenous nitric oxide and native EDRF can directly activate single Ca(2+)
      dependent K+ channels (K+Ca) in cell-free membrane patches without requiring
      cGMP. Under conditions when guanylate cyclase was inhibited by methylene blue,
      considerable relaxation of rabbit aorta to nitric oxide persisted which was
      blocked by charybdotoxin, a specific inhibitor of K+Ca channels. These studies
      demonstrate a novel direct action of nitric oxide on K+Ca channels.

PMID- 7512694
TI  - An RNA-binding protein associated with Src through its SH2 and SH3 domains in
      mitosis.
AB  - The tyrosine kinase activity of c-Src is stimulated during mitosis by
      dephosphorylation of its regulatory tyrosine residue. This is associated with
      increased accessibility of its Src homology-2 (SH2) domain for binding a
      phosphotyrosine-containing peptide. But physiological targets of activated c-Src
      in mitosis have not yet been identified. Here we report that a 68K protein (p68)
      becomes tyrosine-phosphorylated and physically associates with Src during mitosis
      in mouse fibroblasts. p68 independently binds the Src SH2 and SH3 domains in
      vitro and both domains are required for p68 phosphorylation and binding in vivo.
      p68 is closely related to the p62 protein that is associated with the Ras GTPase
      activating protein (GAP) and selectively binds, directly or indirectly,
      polyribonucleotides. Because the Src SH3 domain also binds heterogeneous nuclear
      ribonucleoprotein K, these results raise the intriguing possibility that c-Src
      may regulate the processing, trafficking or translation of RNA in a cell-cycle
      dependent manner.

PMID- 7512693
TI  - Cloning and functional expression of a cyclic-nucleotide-gated channel from
      mammalian sperm.
AB  - Cyclic nucleotide-gated (CNG) channels serve as downstream targets of signalling
      pathways in vertebrate photoreceptor cells and olfactory sensory neurons (see
      ref. 1 for review). Ca2+ ions that enter through CNG channels intimately control
      these signalling pathways by regulating synthesis or hydrolysis of cyclic
      nucleotides, and by decreasing ligand sensitivity of CNG channels. Several lines
      of evidence suggest that cyclic nucleotides and Ca2+ play important roles in
      chemotaxis of invertebrate sperm and fertilization (see ref. 9 for review),
      whereas their mechanisms of action in vertebrate sperm are largely unknown. Here
      we report the cloning and functional expression of a novel CNG channel from
      bovine testis. The channel polypeptide was functionally localized in sperm, but
      is also specifically expressed in cone photoreceptor cells. These channels might
      be involved in chemotaxis of sperm by controlling Ca2+ entry through a cyclic
      nucleotide signalling pathway.

PMID- 7512697
TI  - Synthesis and biological activity of NK1 tachykinin antagonists not containing D
      residues.
AB  - A series of analogues of the previously reported NK1 tachykinin antagonist [Orn6,
      Glu(OBzl)11]-SP6-11-OBzl has been synthesized and tested in order to investigate
      the effects on antagonistic activity of modifications at the C-terminal residue.
      The biological activity in the guinea-pig ileum assay (NK1 receptor) indicates
      that the two aromatic rings introduced in the C-terminal part of the peptide are
      both essential for the expression of antagonistic activity.

PMID- 7512695
TI  - A target for Src in mitosis.
AB  - The activity of the c-Src protein is increased during cell-cycle stage G1 in
      fibroblasts stimulated with certain growth factors, and at the G2/M transition,
      but little is known about Src substrates in these circumstances. In contrast,
      cells transformed with activated Src contain many tyrosine-phosphorylated
      proteins. We compared the phosphotyrosine content of growing and mitotically
      arrested Src-transformed cells. We report here that although phosphorylation of
      most proteins was unchanged during mitosis, phosphorylation of one of about 68K
      was greatly enhanced. The p68 was physically associated with activated c-Src, and
      it bound to the SH3 domain of c-Src in vitro. Tyrosine-phosphorylated p68 was
      also present in mitotic extracts of normal cells, suggesting that its
      phosphorylation was not just a consequence of transformation. Purification and
      microsequencing of p68 showed that it was related to the previously described GAP
      associated protein p62 (ref. 6).

PMID- 7512698
TI  - Brain cholecystokinin octopeptide (CCK-8) concentrations: effect of tryptophan
      and other serotonergic agents.
AB  - The effects of 1-week drug treatment on the brain contents of neuropeptides were
      investigated. The cholecystokinin (CCK) concentrations in the hypothalamus were
      significantly decreased by tryptophan treatment but not by imipramine and
      cyproheptadine, which changed the serotonergic function. Proglumide, the CCK
      antagonist, induced in the hypothalamic and hippocampal-striatal areas an
      increase in CCK concentration, which was not reversed in the presence of
      tryptophan. Dynorphin and substance P(SP) concentrations were also modified by
      proglumide treatment.

PMID- 7512696
TI  - Evidence for tachykinin NK-2 receptors in guinea-pig airways from binding and
      functional studies, using [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10).
AB  - The potent contractile responses of guinea-pig airways to neurokinin A (NKA) and
      neuropeptide gamma (NP gamma) are thought to be mediated by NK-2 receptors.
      However, NK-2 binding sites are not detectable using the radioligand [125I]
      iodohistidyl-NKA. Here, a novel, highly selective iodinated radioligand, [125I]
      [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10), and a number of related peptides have
      been used to characterize NK-2 receptors on guinea-pig airways, using binding and
      functional studies. Specific binding of [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4
      10), was saturable and to a single high affinity site, with KD 1.29 +/- 0.36 nM
      (n = 4). The rank order of potency for tachykinins and analogues as competitors
      for the binding was: [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) > or = NP gamma > or
      = [Lys5,MeLeu9,Nle10]-NKA(4-10) > NKA > or = SR 48968 >> MDL 29913 > or =
      substance P (SP) = [127I]-Bolton-Hunter NKA (BHNKA) > or = MEN 10207 > neurokinin
      B (NKB). Septide, [DPro9,Pro10,Trp11]-SP, the NK-1 selective ligands
      [Sar9,Met(O2)11]-SP, [Pro9]-SP and CP 96345, the NK-3 selective senktide, and
      calcitonin gene-related peptide (CGRP) were weak or ineffective. On guinea-pig
      isolated bronchi, the potency order of contractile agonists was:
      [Lys5,MeLeu9,Nle10]-NKA(4-10) > NKA > or = NP gamma > or = [Lys5,Tyr7,MeLeu9,
      Nle10]-NKA(4-10) > or = septide = BHNKA > or = [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4
      10) > or = [Sar9,Met(O2)11]-SP > or = NKB = [Pro9]-SP > or = SP >>
      senktide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512699
TI  - The effect of neuropeptides on the release of neurotransmitter amino acids from
      rat striatum.
AB  - Neuropeptide Y (NPY), peptide YY (PYY), and galanin are found throughout the
      central nervous system with appreciable levels occurring in the striatum. In this
      study we have investigated the effects of these peptides on the potassium
      stimulated release of endogenous neurotransmitter amino acids from slices of rat
      striatum. The release of glutamate was significantly reduced by nanomolar
      concentrations of each peptide, whilst the release of aspartate, gamma
      aminobutyric acid (GABA) and glycine was not affected. The reduction in release
      due to galanin (200 nM) was inhibited by glibenclamide (5 microM). These results
      support the view that NPY, PYY and galanin modulate neurotransmitter release
      possibly by a presynaptic action. The results with glibenclamide suggest that the
      action of galanin is mediated through an ATP-sensitive potassium channel.

PMID- 7512700
TI  - Expression of PAC 1, an epitope associated with two synapse-enriched
      glycoproteins and a neuronal cytoskeleton-associated polypeptide in developing
      forebrain neurons.
AB  - The monoclonal antibody PAC 1 (postsynaptic density and cytoskeleton enriched)
      recognizes an epitope present on two postsynaptic density-enriched glycoproteins
      of 130,000 (postsynaptic density-enriched glycoprotein 130) and 117,000 mol. wt
      (postsynaptic density-enriched glycoprotein 117), and a cytoskeleton-enriched
      polypeptide of 155,000 mol. wt (cp155). The PAC 1 antibody has been used to study
      the development of the PAC 1 antigens in the developing rat forebrain in vivo and
      in tissue culture. cp155 is detected by embryonic day 14 and its level continues
      to rise until the sixth postnatal week. Postsynaptic density-enriched
      glycoproteins 130 and 117 are also expressed in embryonic brain although the
      level of postsynaptic density-enriched glycoprotein 130 initially increases more
      rapidly than that of postsynaptic density-enriched glycoprotein 117. Peak values
      are observed at postnatal days 4 (postsynaptic density-enriched glycoprotein 117)
      and 9 (postsynaptic density-enriched glycoprotein 130). The level of post
      synaptic density-enriched glycoprotein 117 subsequently decreases to some 50% of
      the peak value by postnatal day 42. Immunocytochemical studies show that PAC 1
      immunoreactivity in developing cerebral cortex, detectable by postnatal day 0, is
      primarily associated with the perikarya and dendrites of pyramidal cells. The
      immunoreactivity develops as patches of PAC 1-positive neurons, uniform staining
      of the cortex only being fully established after postnatal day 9. Double
      immunofluorescence labelling studies of forebrain cultures prepared from
      embryonic day 18 animals shows that many, but not all, growth-associated protein
      43-positive neurons exhibit PAC 1 immunoreactivity. Some non-neuronal cells also
      stain with the PAC 1 monoclonal antibody. The growth cones of cultured neurons
      exhibit PAC 1 immunoreactivity and the PAC 1 antigens are detected on
      immunodeveloped western blots of isolated growth cones. The PAC 1 epitope is
      intracellular, but immunoreactivity does not co-localize with F-actin as detected
      by rhod-amine-phalloidin or with tubulin immunoreactivity. Postsynaptic density
      enriched glycoprotein 130 is readily detected on PAC 1 immunodeveloped western
      blots of forebrain cultures maintained for up to 14 days in vitro. Postsynaptic
      density-enriched glycoprotein 117 is only poorly expressed by these cultures. The
      PAC 1 glycoproteins are present in forebrain synaptic membranes and postsynaptic
      densities at an early stage of development. The synaptic membrane level of
      postsynaptic density-enriched glycoprotein 130 and postsynaptic density-enriched
      glycoprotein 117 increases markedly between postnatal days 3 and 8. The level of
      both glycoproteins detected in postsynaptic densities remain virtually constant
      from postnatal days 9-90. These results are consistent with functional roles for
      these molecules in neuronal and synapse development.

PMID- 7512701
TI  - L-type Ca2+ channel is involved in the regulation of spontaneous transmitter
      release at developing neuromuscular synapses.
AB  - Involvement of an L-type Ca2+ channel in the regulation of spontaneous
      transmitter release was studied in Xenopus nerve-muscle cultures. The frequency
      of spontaneous synaptic currents, which reflects impulse-independent
      acetylcholine release from the nerve terminals, showed a marked increase in high
      K+ medium or after treatment with a phorbol ester, 12-O-tetradecanoyl-phorbol 13
      acetate, a drug that activates protein kinase C and depolarizes the presynaptic
      neuron. The potentiation effect of high K+ and 12-O-tetradecanoyl-phorbol 13
      acetate requires Ca2+ influx through the L-type Ca2+ channel in the plasma
      membrane, since it was significantly reduced by the presence of nifedipine,
      verapamil or diltiazem and enhanced by Bay K 8644, an L-type Ca2+ channel
      agonist. It was shown recently that adenosine 5'-triphosphate markedly
      potentiates the spontaneous acetylcholine release at these synapses through the
      binding of P2-purinoceptors and the activation of protein kinase C. We found in
      the present study that potentiation effects of adenosine 5'-triphosphate are
      inhibited by L-type Ca2+ channel blockers, suggesting that the L-type Ca2+
      channel is responsible for the positive regulation of spontaneous acetylcholine
      secretion by adenosine 5'-triphosphate at the developing neuromuscular synapses.
      Our data suggest that modulation of the L-type Ca2+ channel in embryonic motor
      nerve terminals is important for the regulation of spontaneous transmitter
      release.

PMID- 7512702
TI  - Subpopulations of neonatal rat sensory neurons express functional
      neurotransmitter receptors which elevate intracellular calcium.
AB  - We have attempted to identify which subpopulations of rat sensory neurons possess
      functional neurotransmitter receptors which elevate the free concentration of
      intracellular calcium. Subpopulations of sensory neurons were identified using
      three accepted criteria: (i) the distribution and proportion of neurons with
      differing somatic diameters; (ii) the expression of substance P-like
      immunoreactivity; and (iii) the responsiveness of each neuron to capsaicin. The
      total neuronal population was primarily grouped into three classes according to
      somatic diameter and defined as small- (< 17 microns), intermediate- (17-25
      microns) and large- (> 25 microns) sized neurons. It was not possible to
      distinguish between small and intermediate-sized neurons since a similar
      percentage of each class expressed substance P-like immunoreactivity or
      sensitivity to capsaicin. Large-sized neurons did not possess these
      characteristics and, therefore, represented a distinct neuronal population. In
      single, intact neurons of differing diameter, the ability of a variety of
      receptor agonists to elevate the free concentration of intracellular calcium was
      determined using the calcium-sensitive indicator, Fura-2. Local application of
      capsaicin, adenosine, bradykinin, ATP and substance P elevated the resting level
      of the free concentration of intracellular calcium in small and intermediate
      sized neurons. The large-sized neurons were unresponsive to these receptor
      agonists with the exception of ATP. The response to ATP was relatively transient
      in nature and did not differ between neurons of differing somatic
      diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512703
TI  - Effects of target depletion on adult mammalian central neurons: morphological
      correlates.
AB  - The morphological sequelae induced by target removal were studied on adult cat
      abducens internuclear neurons at both the somata and terminal axon arborization
      levels. The neuronal target--the medial rectus motoneurons of the oculomotor
      nucleus--was selectively destroyed by the injection of toxic ricin into the
      medial rectus muscle. Retrograde labeling with horseradish peroxidase
      demonstrated the survival of the entire population of abducens internuclear
      neurons up to one year after target removal. However, soma size was reduced by
      about 20% three months postlesion and maintained for one year. At the
      ultrastructural level, a considerable deafferentation of abducens internuclear
      neurons was observed at short intervals (i.e. 10 days after lesion). Large
      regions of the plasmalemma appeared devoid of presynaptic boutons but were
      covered instead by glial processes. The detachment of synaptic endings was
      selective on abducens internuclear neurons since nearby motoneurons always showed
      a normal synaptic coverage. By one month, abducens internuclear neurons recovered
      a normal density of receiving axosomatic synapses. Anterogradely biocytin-labeled
      axon terminals of abducens internuclear neurons remained in place after the
      lesion of medial rectus motoneurons, although with a progressive decrease in
      density. Ultrastructural examination of the oculomotor nucleus 10 days after the
      lesion revealed numerous empty spaces left by the dead motoneurons. Targetless
      boutons were observed surrounded by large extracellular gaps, still apposed to
      remnants of the postsynaptic membrane or, finally, ensheathed by glial processes.
      At longer intervals (> one month), the ultrastructure of the oculomotor nucleus
      was re-established and labeled boutons were observed contacting either
      unidentified dendrites within the neuropil or the soma and proximal dendrites of
      the oculomotor internuclear neurons, that project to the abducens nucleus.
      Labeled boutons were never found contacting with the oculomotor internuclear
      neurons either in control tissue or at short periods after ricin injection. These
      results indicate that the availability of undamaged neurons close to the lost
      target motoneurons might support the long-term survival of abducens internuclear
      neurons. Specifically, the oculomotor internuclear neurons, which likely suffer a
      partial deafferentation after medial rectus motoneuron loss, constitute a
      potential new target for the abducens internuclear neurons. The reinnervation of
      a new target might explain the recovery of synaptic and firing properties of
      abducens internuclear neurons after medial rectus motoneuron lesion, which
      occurred with a similar time course, as described in the accompanying paper [de
      la Cruz R. R. et al. (1994) Neuroscience 58, 81-97.].

PMID- 7512705
TI  - Expression of E-selectin in the human kidney.

PMID- 7512704
TI  - Effects of target depletion on adult mammalian central neurons: functional
      correlates.
AB  - The physiological signals and patterns of synaptic connectivity that CNS neurons
      display after the loss of their target cells were evaluated in adult cats for one
      year. Abducens internuclear neurons were chosen as the experimental model because
      of their highly specific projection onto the medial rectus motoneurons of the
      oculomotor nucleus. Selective death of medial rectus motoneurons was induced by
      the injection into the medial rectus muscle of ricin, a potent cytotoxic lectin
      that leaves the presynaptic axons intact. The electrical activity of
      antidromically identified abducens internuclear neurons was recorded in chronic
      alert animals, during both spontaneous and vestibularly induced eye movements,
      before and after target removal. During the three weeks that followed ricin
      injection, abducens internuclear neurons exhibited several firing-related
      abnormal properties. There was an overall reduction in firing rate with a
      corresponding increase in the eye position threshold for recruitment. In
      addition, neuronal sensitivities to eye position and velocity were significantly
      decreased with respect to control data. Bursting activity was also altered since
      low-frequency delayed burst accompanied the saccades in the on-direction and,
      occasionally, internuclear neurons exhibited low-frequency discharges associated
      with off-directed saccades. Intracellular recordings carried out seven and 15
      days after ricin injection demonstrated no significant changes in their
      electrical properties, although a marked depression of synaptic transmission was
      evident. The amplitude of both excitatory and inhibitory postsynaptic potentials
      of vestibular origin was reduced by 60-85% with respect to controls. However,
      postsynaptic potentials recorded one month after ricin injection showed normal
      amplitude values which persisted unaltered one year after target loss. Recovery
      of synaptic transmission occurred at the same time as the re-establishment of
      normal eye-related signals in the discharge pattern of abducens internuclear
      neurons recorded in alert cats from days 25-30 post lesion. The functional
      restoration of firing properties was maintained in the long term (one year).
      Conversely, abducens motoneurons showed normal firing and synaptic patterns at
      all time intervals analysed. These results demonstrate that, after an initial
      period of altered physiological properties, abducens internuclear neurons survive
      the loss of their target motoneurons and regain a normal discharge pattern and
      afferent synaptic connections.

PMID- 7512706
TI  - Triploid partial molar pregnancy detected through maternal serum alpha
      fetoprotein and HCG screening.
AB  - BACKGROUND: Screening for Down syndrome using maternal serum alpha-fetoprotein
      (MSAFP) and hCG, with or without unconjugated estriol (E3), has become standard
      practice in much of the United States. When both MSAFP and hCG are elevated, the
      possibility of a partial molar pregnancy with fetal neural tube or abdominal-wall
      defect should be added to the differential diagnosis, as illustrated by this
      case. CASE: A 22-year-old woman had elevated MSAFP and hCG levels on routine
      screening at 16 weeks' gestation. Ultrasound examination suggested a neural tube
      defect and a thickened placenta. Amniocentesis was performed. She very rapidly
      developed preeclampsia. Fluorescence in situ hybridization showed three distinct
      spots for the three probes tested. A triploid karyotype was confirmed with
      standard cytogenetic analysis. The fetus had an open neural tube defect, and
      placental pathology was consistent with a partial hydatidiform mole. CONCLUSIONS:
      A possible partial molar pregnancy with abdominal-wall or open neural tube defect
      should be added to the differential diagnosis for interpreting Down syndrome
      screens when both MSAFP and hCG are elevated. A presumptive diagnosis of
      triploidy using fluorescence in situ hybridization was important in the
      management of this pregnancy.

PMID- 7512707
TI  - [Effect of pyospermia on fertility. Studies by selective leukocyte staining,
      elastase determination and routine sperm parameters].
AB  - The effect of cellular immune response on male fertility was investigated. 92
      patients--attending the out patient practice of our Andrological department and
      15 patients undergoing vasectomy for sterilisation purpose--were included in this
      study. For measuring the cellular immune response granulocyte concentration and
      PMN-elastase level were investigated in ejaculate, former according to WHO
      manual, and PMN-elastase concentration by ELISA technic. Elastase is a very
      sensitive non organ specific marker of inflammation. Pathological granulocyte
      concentration was present in 10.8%, slightly elevated level in 4.3% of cases,
      totally in 15.1%. Pathological elastase level was found in 17.4%, slightly
      elevated in 16.3%, totally in 33.7% of cases. High level of correlation was
      present between the two parameters of inflammation r = 0.695. The incidence of
      the two parameters in fertile and subfertile patients groups was not significant.
      Conventional spermaparameters (cell concentration/ml, motility %, intensive
      motility %, morphology %) were significantly different in the leucospermic and
      non leucospermic patient groups, except cell concentration. (P = 0.06, P = 0.04,
      P = 0.03, P = 0.001). The incidence of high elastase level was very similar P =
      0.07, P = 0.005, P = 0.03, P = 0.005. As conclusion of our investigation we
      conclude that cellular response could have a negative influence on male fertility
      as "side-effect" of the cytotoxic influences of immune defense.

PMID- 7512708
TI  - Neonatal guanethidine sympathectomy suppresses autotomy and prevents changes in
      spinal and supraspinal monoamine levels induced by peripheral deafferentation in
      rats.
AB  - In the rat, sciatic and saphenous nerve section resulted in self-mutilation of
      the ipsilateral limb. Fifteen and 60 days after surgery, monoamine levels were
      altered not only in the spinal cord but also in supraspinal structures. Thus, in
      the ipsi- and contralateral sides of the spinal lumbar region, an increase in the
      levels of 5-hydroxyindoleacetic acid (5-HIAA) was observed 15 days after surgery
      and in the levels of serotonin (5-HT) and noradrenaline 60 days later. Changes in
      the content of 5-HT and its metabolite were also evident, at these time points,
      in periaqueductal gray matter and trigeminal nucleus. Chemical sympathectomy
      carried out by administering guanethidine to neonatal rats reduced the degree of
      autotomy and suppressed the changes in monoaminergic systems following peripheral
      neurectomy. This study supports the hypothesis that the local noradrenaline
      outflow from sympathetic fibers in the neuroma is one of the causal factors in
      autotomy and it indicates that autotomy is under the control of descending
      monoaminergic pathways originating in brain-stem nuclei.

PMID- 7512709
TI  - The NMDA receptor antagonists, LY274614 and MK-801, and the nitric oxide synthase
      inhibitor, NG-nitro-L-arginine, attenuate analgesic tolerance to the mu-opioid
      morphine but not to kappa opioids.
AB  - Once daily s.c. administration of 5 mg/kg morphine, a mu-opioid agonist, or
      U50488H (U50), a kappa 1-opioid agonist, for 5 days in male CD-1 mice results in
      a 2-3-fold shift to the right of the respective analgesic (tail flick) dose
      response curves, indicating the development of tolerance. Concurrent s.c.
      administration of the competitive NMDA receptor antagonist, LY274614 (LY), at 24
      mg/kg/24 h infusion (osmotic pump) or 6 mg/kg i.p. once daily attenuates the
      development of morphine tolerance, when the response to saline plus morphine is
      compared on day 5 with LY plus morphine. Using this paradigm, once daily
      administration of either the non-competitive NMDA antagonist, MK-801, at 0.3
      mg/kg i.p. or the nitric oxide synthase inhibitor, NG-nitro-L-arginine (NorArg),
      at 1 mg/kg i.p. twice daily attenuated the development of morphine tolerance.
      None of these drugs modify the tail-flick response or alter the ED50 for
      morphine. In contrast, co-administration of LY, MK-801 or NorArg, as above,
      failed to attenuate the development of tolerance to U50 or to the kappa 3-opioid
      agonist, naloxone benzoylhydrazone (NalBzoH). These results suggest that mu
      opioid tolerance but not kappa 1- or kappa 3-opioid tolerance involves the
      mediation of NMDA receptors and the nitric oxide system.

PMID- 7512711
TI  - Developmental surveillance by pediatric nurses.
AB  - When children at risk for developmental variation are identified at a young age,
      their chances of success in school and in the future can be greatly enhanced
      through early intervention programs. Pediatric nurses in community and acute care
      settings are in key positions to identify children "at risk" and to make
      appropriate referrals. Nurses are encouraged to engage in "developmental
      surveillance," that is, a continuous awareness of all activities relating to the
      detection of developmental problems and the promotion of development during
      primary child care. A parental interview of six questions can assist the nurse in
      developmental surveillance and the identification of developmental variations.
      Once a child is identified as "at risk" the nurse should initiate referrals for
      more thorough evaluation, diagnosis, and, if warranted, intervention.

PMID- 7512712
TI  - The nurse whose specialty is developmental disabilities.
AB  - Specialization in pediatric nursing continues to expand as nurses meet the needs
      of children with special health care needs. The nurse whose specialty is
      developmental disabilities works with a unique population to assist them in both
      obtaining their maximal level of functioning and health, and obtaining the
      resources necessary to lead a quality life. This article describes the roles of
      this nurse.

PMID- 7512713
TI  - Making sense of leeches.

PMID- 7512710
TI  - Immunolocalization and characterization of the low molecular weight antigen (4-5
      kDa) of Toxoplasma gondii that elicits an early IgM response upon primary
      infection.
AB  - A striking feature of toxoplasmic seroconversion is the prominent and early IgM
      response to a low molecular weight antigen of 4-5 kDa. Two different monoclonal
      antibodies directed against the 4-5 kDa antigen have been generated and used to
      characterize this molecule. Using these monoclonal antibodies, we could
      demonstrate the surface localization of the low M(r) antigen by
      immunofluorescence and immuno-electron microscopy assays. By immunoblotting, we
      observed that one of the monoclonal antibodies was unable to recognize the 4-5
      kDa antigen in tachyzoites propagated in cell culture, indicating an epitope
      variability between Toxoplasma gondii tachyzoites grown in vivo and in vitro. We
      discuss the implications of this latter finding in the design of diagnostic
      reagents.

PMID- 7512714
TI  - Transfer of lindane and pentachlorobenzene from mother to newborn rabbits.
AB  - After administration of gamma-hexachlorocyclohexane (lindane) (30 mg/kg) to
      sixteen pregnant rabbits, the transfer and distribution of this insecticide and
      its metabolite pentachlorobenzene, in foetuses and newborns at the 5th, 10th and
      20th days after birth, were investigated. Over one lactation the mothers excreted
      via the milk about 30% of the lindane present in tissues at the 28th day of
      pregnancy. The total amount of lindane transferred via milk to 5 day-old newborns
      was higher than that transferred across the placenta during pregnancy. Lindane
      concentrations in newborns decreased in spite of the efficient transfer to off
      spring by lactating mothers. This cannot be explained by growth alone and
      indicates that newborns are able to actively metabolize the insecticide. The
      pentachlorobenzene metabolite produced after lindane administration to the
      mothers crossed the placental barrier with difficulty during pregnancy, but was
      readily transferred to off-spring via milk. Pentachlorobenzene levels in neonates
      increased during lactation by transfer and also as a consequence of endogenous
      production. At the 20th day of lactation the pentachlorobenzene concentration in
      maternal and foetal tissues was higher than that of lindane.

PMID- 7512716
TI  - Lymphoepithelioma-like carcinoma of the breast.
AB  - Lymphoepithelioma describes an undifferentiated carcinoma of the nasopharyngeal
      region characterized by a pronounced reactive lymphocytic infiltrate, often
      obscuring the neoplastic epithelial component. In recent years, histologically
      similar lesions have been reported in a number of other sites. We report such a
      lesion in the breast of a 65-yr-old woman; this site of involvement has not
      previously been described. The unusual histologic appearance raised other
      diagnostic possibilities and was a dilemma on frozen section. Immunostains for
      epithelial markers were particularly useful in delineating the scant epithelial
      neoplastic elements among the abundant lymphocytic component. In situ
      hybridization for Epstein Barr viral DNA was negative.

PMID- 7512715
TI  - Chlormethiazole and dizocilpine block the behavioural, but not the neurotoxic
      effects of 5,7-dihydroxytryptamine in mice.
AB  - Intracerebroventricular administration to mice of 5,7-dihydroxytryptamine at a
      dose of 300 micrograms resulted in convulsive behaviour and death (latency 7.6 +/
      1.7 min.). Pretreatment with dizocilpine or chlormethiazole resulted in a dose
      dependent inhibition of the convulsive behaviour. A dose of dizocilpine of 0.12
      mumol/kg or chlormethiazole at a dose of 150 mumol/kg prevented seizures for 30
      min. Injection of 5,7-dihydroxytryptamine (75 micrograms,
      intracerebroventricularly) produced an approximate 50% neurotoxic loss of
      cerebral 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindole acetic
      acid (5-HIAA) 8 days later. This loss was not prevented by administration of
      either dizocilpine (4.5 mumol/kg intraperitoneally) or chlormethiazole (300
      mumol/kg intraperitoneally) given 5 min. before and 55 min. after the 5,7
      dihydroxytryptamine injection. It is proposed that chlormethiazole and
      dizocilpine may protect against 5,7-dihydroxytryptamine-induced seizures because
      of their anticonvulsant activity, but that they do not prevent the neurotoxic
      effects of the compound. The data also suggest that the neurotoxic effects of
      substituted amphetamines such as 3,4-methylene dioxymethamphetamine (MDMA or
      Ecstasy) do not result from the formation of a 5,7-dihydroxytryptamine like
      compound.

PMID- 7512717
TI  - Correspondence re: Tatusuo Tomita, Timothy Dalton, Simon Kwok, Saing Lee, Mark
      Noble, and Masahiro Chiga. Profile of prostatic-specific antigen in prostatic
      carcinomas. Mod Pathol 6:259, 1993.

PMID- 7512718
TI  - Endothelial cell markers CD31, CD34, and BNH9 antibody to H- and Y-antigens-
      evaluation of their specificity and sensitivity in the diagnosis of vascular
      tumors and comparison with von Willebrand factor.
AB  - Sixty vascular tumors including 23 angiosarcomas, 300 nonvascular tumors, and
      selected normal tissues were immunohistochemically evaluated with antibodies to
      CD31, CD34, and von Willebrand factor (vWF), and monoclonal antibody BNH9, to
      test the sensitivity and specificity of these markers in the identification of
      endothelial cells and vascular tumors. Formaldehyde-fixed paraffin-embedded
      tissues and avidin biotin complex immunostaining were used. All markers labeled
      normal vascular and lymphatic endothelial cells approximately equally with the
      exception of CD34 which showed inconsistent expression within the lymphatics. In
      addition, antibody to CD31 reacted with platelets and megakaryocytes, CD34 with
      fibroblasts and aortic smooth muscle cells, and BNH9 with many epithelial cells
      including squamous and gastrointestinal epithelia. Antibody to vWF often showed
      significant stromal background staining which made the staining occasionally
      uninterpretable. Benign vascular tumors showed rather uniform staining with all
      antibodies. However, angiosarcomas were heterogeneous; CD31 was positive in
      21/27, CD34 in 25/27 cases, BNH9 in 22/25, and vWF in 18/27 cases. Epithelioid
      hemangioendotheliomas showed consistent labeling for vWF, but were inconsistently
      labeled with antibodies to the other markers. Kaposi's sarcoma was positive for
      both CD31 and CD34. In addition, antibody to CD34 labeled the tumor cells in
      hemangiopericytoma, cerebellar hemangioblastoma, meningioma, most epithelioid
      sarcomas, dermatofibrosarcomas, and in a few other sarcomas. CD31, in turn, was
      not found in sarcomas other than angiosarcomas, but labeled weakly occasional
      carcinomas and mesotheliomas. Many adenocarcinomas and the glandular component of
      synovial sarcoma were BNH9 positive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512719
TI  - Colocalization of nitric oxide synthase and somatostatin immunoreactivity in rat
      dentate hilar neurons.
AB  - Distribution of nitric oxide synthase (NOS), somatostatin (SSN), and parvalbumin
      (PV) was studied in the rat hippocampus by immunohistochemical methods. The aim
      was to explore the interrelationship between SSN-immunoreactive (SSN-IR) neurons
      in the dentate hilus, which have been shown to be vulnerable to a number of
      pathophysiological insults, and the presence or absence of NOS and/or PV in the
      same subset of dentate hilar neurons. Small NOS-IR neurons were scattered in the
      pyramidal, oriens, and radiatum layers of the CA1-CA3 areas and in the subiculum,
      where larger NOS-IR neurons were occasionally noted. In the area dentata, NOS-IR
      neurons, which were composed of small and large polymorphic cells, appeared as a
      single file at the hilar border with the granule cell layer and clustered in the
      hilus in fairly high density. Double-labeling techniques showed that most NOS-IR
      neurons in the hilus were SSN-IR, whereas coexistence of NOS and PV
      immunoreactivity or SSN and PV immunoreactivity was low in dentate hilar neurons.
      In other areas of the hippocampus, colocalization of NOS and SSN in the same
      neurons was much less frequent. Thus, SSN-IR neurons in the dentate hilus
      constitute a population of neurons that contain the enzyme NOS as well. The
      presence of NOS coupled to the lack or low level of PV in this group of neurons
      may provide a neurochemical basis for their high susceptibility to certain
      pathophysiological insults.

PMID- 7512720
TI  - Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor
      receptor and both become tyrosine-phosphorylated after receptor activation.
AB  - Granulocyte-colony-stimulating factor (G-CSF) stimulates the proliferation and
      differentiation of cells of the neutrophil lineage by interaction with a specific
      receptor. Early signal transduction events following G-CSF receptor activation
      were studied. We detected tyrosine phosphorylation of both the G-CSF receptor and
      the protein tyrosine kinase JAK1 following G-CSF binding to the human G-CSF
      receptor. In vitro, the kinase activity of JAK1 was increased by G-CSF
      stimulation. Coimmunoprecipitation of JAK1 with the G-CSF receptor suggested a
      physical association which existed prior to G-CSF stimulation.

PMID- 7512722
TI  - G-->A hypermutation of the human immunodeficiency virus type 1 genome: evidence
      for dCTP pool imbalance during reverse transcription.
AB  - The quasispecies model for RNA viruses predicts the existence of a replication
      error threshold beyond which there is a melting or total loss of sequence
      information. Retroviral G-->A hypermutation is probably an example. Here it is
      shown that G-->A transitions may occur in both GpG and GpA dinucleotide contexts.
      Transitions in GpG preferentially occur via base mispairing at the ends of runs
      of G residues, whereas G-->A transitions within GpA may result from temporary
      dislocation of the primer and template strands by a single base. The two
      circumstances may be related by the local dCTP substrate concentration. An in
      vitro elongation assay shows that primer/template dislocation is more frequent
      for the human immunodeficiency virus type 1 reverse transcriptase than for murine
      or avian retroviral enzymes. Taken together these data suggest that G-->A
      hypermutation is an example of induced mutation whereby the viral reverse
      transcriptase is forced into making errors by imbalances in the intracellular
      dCTP concentration.

PMID- 7512721
TI  - Dynamics of signal transduction after aggregation of cell-surface receptors:
      studies on the type I receptor for IgE.
AB  - Many ligands stimulate cellular responses by aggregating the cell-surface
      receptors to which they are bound. We investigated several mechanistic questions
      related to aggregation of receptors by using the high-affinity receptor for IgE
      (Fc epsilon RI) on mast cells as a model system. We briefly exposed cells to
      covalently cross-linked oligomers of IgE and then added excess monomeric IgE to
      prevent further aggregation. Early events were examined by monitoring the
      phosphorylation of protein tyrosines; later events were examined by monitoring
      secretion. We found that aggregated receptors continue to signal both late and
      early events in the absence of formation of new aggregates. Additional
      experiments suggested that the clustered receptors undergo a dynamic process of
      phosphorylation and dephosphorylation. Our findings suggest that for these and
      related receptors that function by aggregation, the persistence of signal
      transduction is directly related to the intrinsic affinity of the ligand for the
      individual receptor.

PMID- 7512723
TI  - Synthesis of circular RNA in bacteria and yeast using RNA cyclase ribozymes
      derived from a group I intron of phage T4.
AB  - Studies on the function of circular RNA and RNA topology in vivo have been
      limited by the difficulty in expressing circular RNA of desired sequence. To
      overcome this, the group I intron from the phage T4 td gene was split in a
      peripheral loop (L6a) and rearranged so that the 3' half intron and 3' splice
      site are upstream and a 5' splice site and 5' half intron are downstream of a
      single exon. The group I splicing reactions excise the internal exon RNA as a
      circle (RNA cyclase ribozyme activity). We show that foreign sequences can be
      placed in the exon and made circular in vitro. Expression of such constructs (RNA
      cyclase ribozymes) in Escherichia coli and yeast results in the accumulation of
      circular RNA in these organisms. In yeast, RNA cyclase ribozymes can be expressed
      from a regulated promoter like an mRNA, containing 5' leader and 3' trailer
      regions, and a nuclear pre-mRNA intron. RNA cyclase ribozymes have broad
      application to questions of RNA structure and function including end requirements
      for RNA transport or function, RNA topology, efficacy of antisense or ribozyme
      gene control elements, and the biosynthesis of extremely long polypeptides.

PMID- 7512724
TI  - Mice expressing both B7-1 and viral glycoprotein on pancreatic beta cells along
      with glycoprotein-specific transgenic T cells develop diabetes due to a breakdown
      of T-lymphocyte unresponsiveness.
AB  - T lymphocytes have been implicated in the onset of many autoimmune diseases;
      however, the mechanisms underlying T-cell activation toward self antigens are
      poorly understood. To study whether T-lymphocyte costimulation can overcome the
      immunologic unresponsiveness observed in an in vivo model, we have created
      transgenic mice expressing the costimulatory mouse molecule B7-1, a ligand for
      the CD28 receptor, on pancreatic beta cells. We now report that triple-transgenic
      mice expressing both B7-1 and a viral glycoprotein on their beta cells, along
      with T cells expressing the viral-glycoprotein-specific transgenic T-cell
      receptor, all develop insulitis (lymphocytic infiltration of the pancreatic
      islets) and diabetes. In striking contrast, the T cells in double-transgenic mice
      expressing the same viral glycoprotein (but no B7) on their pancreatic beta cells
      and the transgenic T-cell receptor on their T cells, reported earlier, remain
      indifferent to the glycoprotein-expressing beta cells. In fact, all three
      transgenes are required to initiate immune-mediated destruction of the beta
      cells. Mice expressing any of the transgenes alone, or any two in combination,
      maintain normal islet architecture and never spontaneously develop insulitis or
      diabetes. Our results show that aberrant B7 expression on peripheral tissues may
      play an important role in the activation of self-reactive T cells and further
      suggest that abnormal expression of costimulatory receptors may be involved in
      various T-cell-mediated autoimmune diseases.

PMID- 7512725
TI  - Cytoplasmic phospholipase A2 translocates to membrane fraction in human
      neutrophils activated by stimuli that phosphorylate mitogen-activated protein
      kinase.
AB  - The addition of the chemotactic peptide formylmethionylleucylphenylalanine (fMet
      Leu-Phe) to human neutrophils pretreated with the cytokine granulocyte/macrophage
      colony-stimulating factor (GM-CSF) results in a 10-fold enhanced activity of
      phospholipase A2, measured as the release of arachidonic acid. It is found that
      GM-CSF increases the tyrosine phosphorylation, enhances the activity of a mitogen
      activated protein kinase, and greatly potentiates the fMet-Leu-Phe-induced
      tyrosine phosphorylation and enhanced activity of this kinase. Stimuli that
      increase the tyrosine phosphorylation, enhance the activity of the mitogen
      activated protein kinase, and cause a rise in the intracellular concentration of
      free calcium increase the amount of phospholipase A2 associated with the plasma
      membrane. This increase corresponds to a decrease in the amount found in the
      cytosol. Whereas GM-CSF alone produces only a small increase in the amount of
      phospholipase A2 associated with the membrane, it potentiates greatly the fMet
      Leu-Phe-induced increase. The total amount (whole cell) of phospholipase A2, as
      measured by immunoblotting using anti-phospholipase A2 antibody, does not change
      upon stimulation of human neutrophils with GM-CSF, fMet-Leu-Phe, or both. In
      addition, the band that corresponds to phospholipase A2 is shifted upward in
      membrane isolated from neutrophils stimulated with fMet-Leu-Phe, suggesting that
      the enzyme has been altered, possibly phosphorylated, though not on tyrosine
      residues. A working hypothesis is presented. Briefly, stimulation of human
      neutrophils with GM-CSF, in the absence of an additional stimulus, increases the
      tyrosine phosphorylation and activation of a mitogen-activated protein kinase,
      which in turn phosphorylates and activates cytoplasmic phospholipase A2. In the
      presence of an increased intracellular concentration of free calcium the
      phospholipase A2 is translocated to the plasma membrane where its substrate is
      located. GM-CSF also potentiates greatly the fMet-Leu-Phe-induced tyrosine
      phosphorylation and activation of a mitogen-activated protein kinase and, since
      fMet-Leu-Phe causes an intracellular calcium rise, the amount of the
      phospholipase A2 that is associated with the membrane fraction.

PMID- 7512726
TI  - Functional domains of the receptor-associated protein (RAP).
AB  - The receptor-associated protein (RAP) specifically associates with gp330 and the
      low density lipoprotein (LDL) receptor-related protein (LRP), the two newest
      members of the LDL receptor gene family. Results obtained by ligand blotting,
      affinity chromatography, and density-gradient sedimentation demonstrate that RAP
      binds to both receptors with high affinity and that the binding is Ca2+
      dependent. RAP also binds heparin and is identical to a mouse heparin binding
      protein (HBP-44) identified in a teratocarcinoma cell line (F9). While
      biochemical studies have shown that RAP is present on the cell surface and is an
      effective inhibitor of ligand binding to gp330 and LRP, immunocytochemical
      findings indicate that RAP is most abundant in the endoplasmic reticulum lumen
      and may function in receptor folding and/or trafficking. To facilitate the
      characterization of RAP's function(s) we have mapped its gp330 and heparin
      binding sites by performing direct binding studies on fusion proteins
      representing overlapping domains of RAP. gp330 was found to bind to two separate
      sites on RAP--i.e., between amino acids 85-148 and 178-248. Binding studies with
      radiolabeled heparin indicate that the heparin binding site is between amino
      acids 261 and 323, which is consistent with our previously proposed site
      (residues 287-306) based on the amphipathic nature of the C terminus of RAP.
      These data demonstrate that the gp330 and heparin binding sites and the Heymann
      nephritis pathogenic epitope (amino acids 1-86) demonstrated earlier are
      represented by distinct domains of the RAP polypeptide.

PMID- 7512729
TI  - The Arabidopsis thaliana apurinic endonuclease Arp reduces human transcription
      factors Fos and Jun.
AB  - An Arabidopsis thaliana cDNA encoding an analogue, referred to as Arp for
      apurinic endonuclease-redox protein, of the human redox factor REF has been
      cloned. Arp stimulates in vitro DNA-binding activity of the human transcription
      factor Jun and Fos by the reduction of a cysteine residue located in the DNA
      binding domain. Based on amino acid sequence homology, this redox activity is
      probably confined to the small internal domain of the Arp protein. In analogy to
      REF, we show that the Arabidopsis Arp protein also functions as an
      apurinic/apyrimidinic class II endonuclease. This base-free endonuclease activity
      resides in the carboxyl-terminal domain, and this part of the protein has
      significant sequence similarity to bacterial (Escherichia coli exonuclease III
      and Streptococcus pneumoniae exonuclease A) and animal (Drosophila Rrp1 and human
      REF/HAP) apurinic/apyrimidinic endonucleases. The amino-terminal domain of the
      Arp protein is highly charged and apparently increases the affinity of the
      protein for DNA. Therefore, the Arabidopsis Arp protein is multifunctional and
      may be involved both in DNA repair and in the regulation of transcription.

PMID- 7512727
TI  - Immunosuppressant FK506 promotes neurite outgrowth in cultures of PC12 cells and
      sensory ganglia.
AB  - The immunosuppressant drug FK506 acts by binding to receptor proteins, FK506
      binding proteins (FKBPs), which in turn can bind to and regulate a Ca(2+)
      dependent phosphatase, calcineurin, and a Ca2+ release channel, the ryanodine
      receptor. Based on our findings in regeneration models that levels of FKBPs
      during neural regeneration parallel those of growth-associated protein GAP43, a
      calcineurin substrate that regulates neurite extension, we examined effects of
      FK506 in PC12 rat pheochromocytoma cells and in rat sensory ganglia. FK506
      enhances neurite outgrowth in both systems by increasing sensitivity to nerve
      growth factor. Blockade of FK506 actions in sensory ganglia by rapamycin, an
      FK506 antagonist, establishes that these effects involve FKBPs. Rapamycin itself
      stimulates neurite outgrowth in PC12 cells. These drug effects are detected at
      subnanomolar concentrations, suggesting therapeutic application in diseases
      involving neural degeneration.

PMID- 7512728
TI  - Activation-dependent phosphorylation of the T-lymphocyte surface receptor CD28
      and associated proteins.
AB  - CD28 is a costimulatory receptor that can provide the second signal necessary for
      T-cell activation and function in response to stimulation through the T-cell
      antigen receptor/CD3 complex. We found that a distinct array of proteins was
      phosphorylated on tyrosine following stimulation with anti-CD28 monoclonal
      antibody, as detected by immune-complex kinase assays. Anti-CD28 stimulation of
      in vitro kinase activity was detergent-dependent, occurring in immune complexes
      prepared with Brij 96 but not Nonidet P-40. Pretreatment of cells with low
      concentrations of phorbol ester increased the activation-independent
      phosphorylation of proteins in CD28 immune complexes. Reimmunoprecipitation
      studies indicated that the cytoplasmic protein-tyrosine kinases Lck and Fyn were
      associated with CD28. CD28 itself was phosphorylated both in vitro and in vivo in
      an activation-dependent manner, as detected by nonreducing/reducing SDS/PAGE
      analyses. The activation-stimulated phosphorylation of CD28 may play a key role
      in signaling through this receptor.

PMID- 7512730
TI  - Cell-adhesion-disrupting action of interleukin 6 in human ductal breast carcinoma
      cells.
AB  - Recombinant baculovirus-derived interleukin 6 (IL-6) disrupts the attachment of
      human ductal breast carcinoma subline ZR-75-1-Tx cells to neighbors and the
      substratum in culture without inhibiting the proliferation of the cells. The
      nonadherent cells lack pseudopodia and do not translocate directionally. These
      findings stand in contrast to the earlier observations in the Ro subline of ZR-75
      1 cells in which IL-6 induces cell-cell separation without detachment of the
      cells from the substratum, with the cells displaying pseudopodia, increased
      motility, and decreased proliferation. The IL-6-induced ZR-75-1-Tx cell
      detachment and rounding are reversible by incubation of the treated cells in IL-6
      free medium for several days. The distinctive changes induced by IL-6 in ZR-75-1
      Ro cells are similarly reversible. Either acidic fibroblast growth factor or
      phorbol 12-myristate 13-acetate can replace serum as a cofactor in IL-6-induced
      ZR-75-1-Tx cell detachment. Our findings indicate that genetic changes can occur
      in breast carcinoma cells that through cytokine action markedly affect cell
      structure, adhesiveness, and motility.

PMID- 7512731
TI  - Neutralization of divergent human immunodeficiency virus type 1 variants and
      primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody.
AB  - The antiviral characteristics of monoclonal antibody IAM-41-2F5 (2F5) were
      determined in cell culture. The antibody had been previously shown to bind a
      specific sequence, ELDKWA, within the external domain of the gp41 envelope
      glycoprotein human immunodeficiency virus type 1 (HIV-1). Selection by 2F5 of
      recombinant phage from an epitope library confirmed the identification of the
      antibody's binding determinant. The antibody was found to be capable of
      neutralizing a broad range of lymphoid cell culture-adapted HIV-1 variants as
      well as HIV-1 primary isolates. Sequence analysis of the latter showed that
      neutralization was related to the presence of the antibody binding site. From
      kinetic measurements using an epitope-containing peptide or gp41, the half-time
      of dissociation for 2F5 was determined to be 122 min for the peptide and 156 min
      for gp41. The region of gp41 expressing this sequence exhibits greater
      conservation among HIV-1 isolates than do the variable domains of gp120.

PMID- 7512733
TI  - Reading the molecular clock from the decay of internal symmetry of a gene.
AB  - The closely related serum albumin, alpha-fetoprotein, and vitamin D-binding
      proteins are derived from a common ancestor, which itself was the result of a
      triplication of an ancestral gene. We have aligned the sequences of these
      proteins against themselves to assess the degree to which the ancestral 3-fold
      symmetry has been retained; in a dot plot, relics of the molecular symmetry
      appear as a series of alignments parallel to the main diagonal. The decay of
      internal symmetry reflects the rate of change of a gene in a single line of
      evolutionary descent. We examined 11 serum albumins, 2 ceruloplasmins, 3 alpha
      fetoproteins, and 3 vitamin D-binding proteins. We have found that ceruloplasmin
      evolves at the same rate in human and rat, whereas albumin, alpha-fetoprotein,
      and vitamin D-binding protein evolve at different rates. The human genes had the
      highest alignment scores, indicating the most preserved ancestral features. We
      conclude that the molecular clock may run at different rates for the same gene in
      different species.

PMID- 7512732
TI  - The human splicing factor ASF/SF2 can specifically recognize pre-mRNA 5' splice
      sites.
AB  - ASF/SF2 is a human protein previously shown to function in in vitro pre-mRNA
      splicing as an essential factor necessary for all splices and also as an
      alternative splicing factor, capable of switching selection of 5' splice sites.
      To begin to study the protein's mechanism of action, we have investigated the RNA
      binding properties of purified recombinant ASF/SF2. Using UV crosslinking and gel
      shift assays, we demonstrate that the RNA binding region of ASF/SF2 can interact
      with RNA in a sequence-specific manner, recognizing the 5' splice site in each of
      two different pre-mRNAs. Point mutations in the 5' splice site consensus can
      reduce binding by as much as a factor of 100, with the largest effects observed
      in competition assays. These findings support a model in which ASF/SF2 aids in
      the recognition of pre-mRNA 5' splice sites.

PMID- 7512735
TI  - Antigenic relationships between chloroplast and cytosolic fructose-1,6
      bisphosphatases.
AB  - Cytosolic fructose-1,6-biphosphatases (FBPase, EC 3.1.3.11) from pea (Pisum
      sativum L. cv Lincoln) and spinach (Spinacia oleracea L. cv Winter Giant) did not
      cross-react by double immunodiffusion and western blotting with either of the
      antisera raised against the chloroplast enzyme of both species; similarly, pea
      and spinach chloroplast FBPases did not react with the spinach cytosolic FBPase
      antiserum. On the other hand, spinach and pea chloroplast FBPases showed strong
      cross-reactions against the antisera to chloroplast FBPases, in the same way that
      the pea and spinach cytosolic enzymes displayed good cross-reactions against the
      antiserum to spinach cytosolic FBPase. Crude extracts from spinach and pea
      leaves, as well as the corresponding purified chloroplast enzymes, showed by
      western blotting only one band (44 and 43 kD, respectively) in reaction with
      either of the antisera against the chloroplast enzymes. A unique fraction of
      molecular mass 38 kD appeared when either of the crude extracts or the purified
      spinach cytosolic FBPase were analyzed against the spinach cytosolic FBPase
      antiserum. These molecular sizes are in accordance with those reported for the
      subunits of the photosynthetic and gluconeogenic FBPases. Chloroplast and
      cytosolic FBPases underwent increasing inactivation when increasing
      concentrations of chloroplast or cytosolic anti-FBPase immunoglobulin G (IgG),
      respectively, were added to the reaction mixture. However, inactivations were not
      observed when the photosynthetic enzyme was incubated with the IgG to cytosolic
      FBPase, or vice versa. Quantitative results obtained by enzyme-linked
      immunosorbent assays (ELISA) showed 77% common antigenic determinants between the
      two chloroplast enzymes when tested against the spinach photosynthetic FBPase
      antiserum, which shifted to 64% when assayed against the pea antiserum. In
      contrast, common antigenic determinats between the spinach cytosolic FBPase and
      the two chloroplast enzymes were less than 10% when the ELISA test was carried
      out with either of the photosynthetic FBPase antisera, and only 5% when the assay
      was performed with the antiserum to the spinach cytosolic FBPase. These results
      were supported by sequencing data: the deduced amino acid sequence of a
      chloroplast FBPase clone isolated from a pea cDNA library indicated a 39,253
      molecular weight protein, with a homology of 85% with the spinach chloroplast
      FBPase but only 48.5% with the cytosolic enzyme from spinach.

PMID- 7512734
TI  - C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the
      Src homology 3 domains of CRK and GRB2/ASH proteins.
AB  - CRK protein, together with GRB2/ASH and Nck proteins, belongs to the adaptor-type
      Src homology (SH)2-containing molecules, which transduce signals from tyrosine
      kinases. Here another guanine nucleotide-releasing protein (GNRP), C3G, has been
      identified as a CRK SH3-binding protein. The nucleotide sequence of a 4.1-kb C3G
      cDNA contains a 3.2-kb open reading frame encoding a 121-kDa protein, and
      antibodies against C3G have been shown to detect a protein of 130-140 kDa. The
      carboxyl terminus of C3G has a peptide sequence homologous to GNRPs for Ras, and
      the expression of this carboxyl terminus region suppresses the loss of CDC25
      function in the yeast Saccharomyces cerevisiae. The C3G protein expressed in
      Escherichia coli binds to CRK and GRB2/ASH proteins. Mutational analysis of C3G
      assigns the SH3 binding region to a 50-amino acid region containing a proline
      rich sequence. The mRNAs of both the C3G and CRK proteins are expressed
      ubiquitously in human adult and fetal tissues. The results of these studies
      suggest that the complex of CRK and C3G, or GRB2/ASH and C3G, may transduce the
      signals from tyrosine kinases to Ras in a number of different tissues.

PMID- 7512736
TI  - Generation of monoclonal antibodies against plant cell-wall polysaccharides. I.
      Characterization of a monoclonal antibody to a terminal alpha-(1-->2)-linked
      fucosyl-containing epitope.
AB  - Monoclonal antibodies (McAbs) generated against rhamnogalacturonan I (RG-I)
      purified from suspension-cultured sycamore maple (Acer pseudoplatanus) cells fall
      into three recognition groups. Four McAbs (group I) recognize an epitope that
      appears to be immunodominant and is present on RG-I from maize and sycamore
      maple, pectin and polygalacturonic acid from citrus, gum tragacanth, and membrane
      glycoproteins from suspension-cultured cells of maize, tobacco, parsley, bean,
      and sycamore maple. A second set of McAbs (group II) recognizes an epitope
      present in sycamore maple RG-I but does not bind to any of the other
      polysaccharides or glycoproteins recognized by group I. Lastly, one McAb, CCRC-M1
      (group III), binds to RG-I and more strongly to xyloglucan (XG) from sycamore
      maple but not to maize RG-I, citrus polygalacturonic acid, or to the plant
      membrane glycoproteins recognized by group I. The epitope to which CCRC-M1 binds
      has been examined in detail. Ligand competition assays using a series of
      oligosaccharides derived from or related to sycamore maple XG demonstrated that a
      terminal alpha-(1-->2)-linked fucosyl residue constitutes an essential part of
      the epitope recognized by CCRC-M1. Oligosaccharides containing this structural
      motif compete with intact sycamore maple XG for binding to the antibody, whereas
      structurally related oligosaccharides, which do not contain terminal fucosyl
      residues or in which the terminal fucosyl residue is linked alpha-(1-->3) to the
      adjacent glycosyl residue, do not compete for the antibody binding site. The
      ligand binding assays also indicate that CCRC-M1 binds to a conformationally
      dependent structure of the polysaccharide. Other results of this study establish
      that some of the carbohydrate epitopes of the plant extracellular matrix are
      shared among different macromolecules.

PMID- 7512739
TI  - Ontogeny of neuropeptides in the rat urinary bladder.
AB  - Urinary bladders of male rats at ages ranging from 1 day to 18 months were
      analysed for their neuropeptide content. NPY was detected at birth, VIP and CGRP
      at 1 week, and SP at 2 weeks. There was then a sharp increase in both the total
      amounts and concentrations of VIP, CGRP and SP until the rats had reached the age
      of 3-4 weeks. The total amount of NPY increased in two surges, between 2-3 weeks
      and between 4-5 weeks. The concentration of NPY showed a biphasic course, a
      decrease during the first two weeks and then an increase. In adults the total
      amounts of substance P and CGRP were higher than in younger animals, whereas that
      of VIP was lower. Following peaks at 3-8 weeks, the concentrations of VIP and
      substance P decreased with age, whereas that of CGRP remained unchanged. NPY was
      not followed beyond 8 weeks. The present findings offer a framework for future
      studies aimed at elucidating the functional role of neuropeptides in the
      regulation of micturition.

PMID- 7512737
TI  - Two classes of proteins and mRNAs in Lilium longiflorum L. indentified by human
      vitronectin probes.
AB  - Vitronectin (VN) is a substrate adhesion molecule, an extracellular matrix
      glycoprotein that facilitates cell adhesion and cell movement in animals. We have
      reported the cross-reactivity of a 55-kD protein in plants with rabbit anti-human
      VN antibodies and the presence of VN-like sequences in plant genomes using a
      human VN cDNA probe. We have extended these studies by using human VN riboprobes
      to detect VN-like mRNAs in lily (Lilium longiflorum L.) and soybean. In both
      species, two mRNAs were detected. We have also identified a new cross-reactive
      protein (41 kD) using a different preparation of human VN antiserum. In lily
      roots five 41-kD isoforms were observed, whereas only three of these isoforms
      accumulated in leaves. Monospecific antibodies prepared against the plant
      proteins cross-reacted with the human VN protein and vice versa. We have purified
      the 41-kD protein using two-dimensional gel electrophoresis, and amino acid
      composition analysis indicates that it is similar in composition to human VN.

PMID- 7512740
TI  - Angiotensin II neurotransmitter actions in paraventricular nucleus are
      potentiated by a nitric oxide synthase inhibitor.
AB  - There is increasing evidence that nitric oxide (NO) plays a role within the
      central nervous system as a novel messenger. Neuronal culture work suggests NO to
      be involved specifically in mediating actions of angiotensin II (ANG). The
      present study examined the potential role of NO within the paraventricular
      nucleus (PVN), a structure involved in mediating the cardiovascular changes
      initiated by activation of the subfornical organ (SFO). The pressor response to
      stimulation of SFO, which can be divided into a short (SD) and long duration (LD)
      component was enhanced following administration of an NO synthase inhibitor (L
      NAME) (SD control: 101 +/- 4 vs. post L-NAME: 145 +/- 10 mmHg.s (P < 0.05); LD
      control: 387 +/- 167 vs. post L-NAME: 1737 +/- 617 mmHg.s (P < 0.05)). This
      effect was specific to activation of SFO efferents as the blood pressure
      responses to either, stimulation of PVN, or systemic administration of
      vasopressin were not potentiated by administration of L-NAME. These findings
      suggest that NO may be acting within PVN to inhibit further release of ANG,
      thereby attenuating the cardiovascular response to stimulation of SFO.

PMID- 7512738
TI  - Canine galanin: sequence, expression and pancreatic effects.
AB  - To determine if dog galanin is a potent inhibitor of dog insulin secretion we
      determined its primary structure from its cloned cDNA, evaluated its expression
      in celiac ganglia and determined its effect on islet hormone secretion. The
      predicted amino acid sequence differs from the other known species of galanin by
      three to six amino acids in the C-terminal half of the molecule. In situ
      hybridization revealed the presence of dog progalanin mRNA in every neuronal cell
      body in the dog celiac ganglion. The predicted dog galanin peptide was
      synthesized and infused i.v. at 0.25, 2.5, 25 or 250 pmol/kg/min. It potently
      inhibited insulin secretion, less potently inhibited pancreatic somatostatin
      release and stimulated glucagon secretion, similar to the effects of porcine
      galanin in the dog. In summary, dog galanin is expressed in the neuronal cell
      bodies that innervate the pancreas and the sequence of the dog galanin preserves
      the potent insulin inhibitory part of the galanin molecule. These data support
      the hypothesis that galanin is a sympathetic neurotransmitter in dog pancreas.

PMID- 7512742
TI  - Ligands for L-selectin: where and how many?

PMID- 7512741
TI  - Methionine enkephalin metabolism by murine macrophage ectopeptidase(s).
AB  - Ectopeptidases which hydrolyze opioid and other neuropeptides have been
      identified in brain, kidney and intestine. In this study, identification of the
      enzymes metabolizing the opioid peptide methionine enkephalin (YGGFM) in murine
      macrophages was undertaken. Incubation of methionine enkephalin with intact
      murine peritoneal macrophages results in five products identified as Y, F, FM,
      GFM and GGFM by amino acid analysis and peptide microsequencing after
      fractionation by HPLC. The spectrum of metabolites results from at least two
      distinct aminopeptidase activities. The enzyme hydrolyzing YGGFM to GGFM is
      identified as the membrane-anchored aminopeptidase N (ApN; EC 3.4.11.2) based on
      its substrate specificity and inhibitor profile. A distinct bestatin and
      amastatin sensitive aminopeptidase catalyzes hydrolysis of GGFM to GFM. The
      macrophage ApN protein has a larger mass and is antigenically distinct from
      murine kidney ApN, which is suggested to result from glycosylation differences
      rather than expression of a distinct protein. The ApN catalytic activity and mRNA
      levels are increased in thioglycollate-elicited as compared to resident
      peritoneal macrophages. RT-PCR analysis identified a 0.7 kb fragment of the ApN
      coding sequence which was identical in mouse kidney and thioglycollate-elicited
      peritoneal macrophages and which has 89% identity with the corresponding rat
      kidney ApN cDNA sequence.

PMID- 7512744
TI  - The alpha 4 beta 1/VCAM-1 adhesion pathway in physiology and disease.

PMID- 7512743
TI  - Glycoprotein ligands of the two endothelial selectins.

PMID- 7512745
TI  - CD44 splice variants; expression on lymphocytes and in neoplasia.

PMID- 7512746
TI  - Aims and ethics of palliative care--the views of a selected group of Polish
      nursing students.
AB  - The purpose of this study was to describe the opinions of a group of Polish
      nursing students in 4-year university programmes on the aims of palliative care.
      A questionnaire was used to collect relevant data. Findings show that the
      students (n = 72) view palliative care as an area of nursing practice requiring a
      complex range of professional and non-professional skills, attitudes and
      predispositions. Findings also indicate the critical opinion of the students
      about the content of academic courses offered by Polish nursing schools and
      departments with respect to palliative care.

PMID- 7512748
TI  - A new patient weighted symptom score system (DAN-PSS-1). Clinical assessment of
      indications and outcomes of transurethral prostatectomy for uncomplicated benign
      prostatic hyperplasia.
AB  - A patient weighted symptom score system, the Danish Prostatic Symptom Score (DAN
      PSS-1), including a disease specific self administered quality of life
      questionnaire, is presented. The model was evaluated pre- and postoperatively in
      29 patients apparently suffering from uncomplicated benign prostatic hyperplasia.
      The score system is based on the severity of 12 symptoms related to bladder
      storage and voiding function, and three questions related to sexual function
      (symptom score). For each of these parameters the patient must also evaluate its
      influence on his daily life (bother score). In the 29 patients with uncomplicated
      benign prostatic hyperplasia (BPH) bother scores exceeded symptom scores for the
      irritative symptoms but not for the obstructive symptoms, and surprisingly the
      symptom score was less improved than the bother score 6 months after
      transurethral resection of the prostate (TUR-P). Furthermore the postvoiding
      dribble was worsened after the operation. We find that this model, DAN-PSS-1,
      assists in creating a solid base for the indication for and the evaluation of
      treatment of uncomplicated BPH.

PMID- 7512747
TI  - The value of a new symptom score (DAN-PSS) in diagnosing uro-dynamic infravesical
      obstruction in BPH.
AB  - INTRODUCTION: A new type of questionnaire for BPH, the DAN-PSS symptom score
      system, was used in an attempt to predict infravesical obstruction determined by
      pressure-flow study. PATIENTS AND METHODS: In 50 consecutive patients a reliable
      questionnaire and a pressure-flow was obtained. RESULTS: Almost none of the
      unobstructed patients had a total obstructed index (TOI) of more than 6, whereas
      this was the case in half of the obstructed patients. This difference was
      statistically significant. DISCUSSION: This study indicates, that if the total
      obstructed index (TOI) is more than 6, the patient most likely have an
      infravesical obstruction. With this limit the DAN-PSS-score system can predict
      infravesical obstruction with a sensitivity of 42% and a specificity of 89%.
      CONCLUSION: With the new concept of combining quantity with quality in a symptom
      score system, a strong correlation between symptoms and objective findings has
      been found.

PMID- 7512749
TI  - [Ion channel mechanism of non-linear integrative function of single neuron in
      brain].

PMID- 7512750
TI  - [Roles of histamine in platelet functions].

PMID- 7512751
TI  - Requirement of vascular integrin alpha v beta 3 for angiogenesis.
AB  - Angiogenesis depends on the adhesive interactions of vascular cells. The adhesion
      receptor integrin alpha v beta 3 was identified as a marker of angiogenic
      vascular tissue. Integrin alpha v beta 3 was expressed on blood vessels in human
      wound granulation tissue but not in normal skin, and it showed a fourfold
      increase in expression during angiogenesis on the chick chorioallantoic membrane.
      In the latter assay, a monoclonal antibody to alpha v beta 3 blocked angiogenesis
      induced by basic fibroblast growth factor, tumor necrosis factor-alpha, and human
      melanoma fragments but had no effect on preexisting vessels. These findings
      suggest that alpha v beta 3 may be a useful therapeutic target for diseases
      characterized by neovascularization.

PMID- 7512752
TI  - The 1990-1991 outbreak of melioidosis in the Northern Territory of Australia:
      epidemiology and environmental studies.
AB  - From November 1990 to June 1991 33 acute cases of melioidosis occurred in the
      Northern Territory, Australia; 25 cases were reported in the capital city,
      Darwin. We carried out an epidemiological investigation to exclude a common
      source outbreak, describe the risk factors for disease, and develop and institute
      appropriate control measures. We compared population based attack rates among
      various risk groups using logistic regression, and the demographic, medical and
      behavioral risk factors for melioidosis by a matched case-control study.
      Environmental Health Officers collected soil, surface water and cooling tower
      water specimens for Pseudomonas pseudomallei culture. The crude attack rate of
      melioidosis during the outbreak was 52 per 100,000. Age, gender, race, diabetes
      and alcohol abuse were independent risk factors for disease. The relative risk of
      disease in diabetic patients was 12.9 (95% CI 5.1-32.7; p < 0.001) and 6.7 in
      alcoholic patients (95% CI 2.9-15.2; p < 0.001). We found no significant
      difference between cases and controls in matched pair analysis for any of several
      exposure factors studied. We isolated Pseudomonas pseudomallei from 4% of soil
      samples and 9% of surface water samples. Our study confirms the importance of
      host factors in the development of melioidosis, and attempts to quantify the risk
      of disease during the Darwin epidemic. Pseudomonas pseudomallei is widespread in
      the soil of urban Darwin.

PMID- 7512753
TI  - Monoclonal antibodies against Schistosoma mekongi surface tegumental antigens.
AB  - Monoclonal antibodies were produced from naturally infected BALB/c mice. Thirteen
      hybridomas which were found to produce monoclonal antibodies against surface
      tegumental antigens of Schistosoma mekongi by ELISA assay were used in this
      study. The antigen specificities of hybridomas reactive with surface tegumental
      antigens were characterized and localized by immunoblotting analysis and Avidin
      Biotin method. Of the 13 hybridomas, only three produced monoclonal antibodies to
      the single epitopes in the surface tegumental antigens. These epitopes (125 kDa,
      97 kDa and 38 kDa) have been found to be the major antigenic components of the
      surface tegument of S. mekongi. The 38 kDa antigen was found to associate with
      the surface tegumental layers, the muscular layers lying just beneath the
      tegument, as well as in the gut surface. The 97 and 125 kDa antigens were
      detectable only in the surface tegumental area. The biochemical identity of these
      proteins or glycoproteins is unknown. However, these antigens have also been
      described in S. japonicum and S. mansoni.

PMID- 7512754
TI  - Immunohistochemical localization of Gnathostoma spinigerum larval antigens by
      monoclonal antibodies: I. Light microscopy.
AB  - Immunohistochemical localization of antigens in advanced third-stage larvae of
      Gnathostoma spinigerum (GsAL3) was studied by indirect enzyme immunostaining
      using 7 G. spinigerum specific monoclonal antibodies, FS-3D11, SS-5H5, SK-6C4, SK
      4E1, SK-7G6, SD-8D4 and SA-9B5. All these MAb belong to the IgG1 subclass and
      only FS-3D11 and SS-5H5 recognize carbohydrate determinants. Each MAb exhibited a
      different reaction pattern and staining intensity in sectioned GsAL3. FS-3D11
      bound primarily to the intestinal brush border whereas SS-5H5 reacted with
      various tissues of the parasite including intestinal epithelium and brush border,
      lateral cords, muscle, pseudocoel, and cuticle. SK-6C4 predominantly stained
      muscle, however, SK-4E1 and SK-7G6 exhibited a lack of labeling. SD-8D4 bound to
      the cuticle and the lateral cords whereas SA-9B5 reacted primarily with the
      pseudocoel. These results suggest that antigens sharing common epitopes are
      present in various structures of the larvae with the intestine being the most
      antigenic site. The present data also suggest that certain GsAL3 antigens
      recognized by the MAb obtained in this study are sensitive to formalin fixation
      and/or paraffin embedding since for 2 out of the 7 MAb staining was negative.

PMID- 7512755
TI  - [The interferon system and natural cytotoxicity functions in patients with acute
      viral hepatitis A and B].

PMID- 7512756
TI  - The incidence of vertical transmission of hepatitis C virus.
AB  - This study was undertaken to clarify the incidence of the vertical transmission
      of hepatitis C virus (HCV). During the third trimester, 2015 pregnant women were
      examined as to anti-HCV antibodies. Anti-HCV antibody seropositive women were
      examined for HCV-RNA in peripheral blood at labor and in breast milk. Their
      offspring were also examined for HCV-RNA in umbilical cord blood and peripheral
      blood one week after birth and during subsequent outpatient visits. The following
      results were obtained: (1) Twelve of the 2015 pregnant women (0.6%) were
      seropositive for anti-HCV antibodies; (2) Seven of the twelve women (58%)
      seropositive for anti-HCV antibodies were also seropositive for HCV-RNA; (3)
      Three newborns of the seven HCV-RNA seropositive women (43%) were found to have
      HCV-RNA in the cord blood; (4) In the three newborns HCV-RNA had disappeared from
      the peripheral blood within one month after birth; (5) Two of the seven HCV-RNA
      seropositive women (29%) had HCV-RNA positive breast milk; (6) The possibility of
      infection via breast milk was shown in one infant at ten months after birth.
      Based on these results, it is indicated that HCV vertical transmission is
      possible in more than half of the HCV-RNA seropositive mothers. However, because
      of the disappearance of HCV from the infants' peripheral blood, further following
      study is needed.

PMID- 7512758
TI  - Defensins: a family of antimicrobial and cytotoxic peptides.
AB  - Defensins are antimicrobial and cytotoxic peptides that contain 29-35 amino acid
      residues, including 6 invariant cysteines that form 3 intramolecular disulfide
      bonds. They constitute more than 5% of the total cellular protein of human and
      rabbit neutrophils (PMN), and are also produced by rabbit lung macrophages and by
      murine and human small intestinal Paneth cells. Defensins exerted antimicrobial
      effects in vitro against many Gram-positive and Gram-negative bacteria, fungi,
      mycobacteria and some enveloped viruses, and were cytotoxic to a wide range of
      normal and malignant targets, including cells resistant to TNF-alpha and NK
      cytolytic factor. Human and rabbit defensins formed voltage-sensitive channels in
      a variety of planar lipid bilayers when a negative voltage of approximately 70-90
      mV was applied to the contralateral side. These channels showed modest anion
      selectivity and their formation was strongly influenced by defensin
      concentration. Although most other channel-forming peptides have prominent alpha
      helical domains, the structure of defensin molecules is primarily composed of
      antiparallel beta-sheets. Studies with various prokaryotic and eukaryotic cells
      provided convincing evidence that defensins killed these targets by forming
      voltage-regulated channels in the susceptible cell's membrane. The broad spectrum
      of defensin-susceptible targets and the abundance of defensins in specialized
      host defense cells of the blood, lungs and intestinal tract suggest that
      defensins could play a significant role in innate immunity to infection and
      neoplasia.

PMID- 7512757
TI  - The stimulatory effects and binding characteristics of PACAP27 in rat dispersed
      pancreatic acini.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a recently isolated
      active peptide of the VIP (vasoactive intestinal peptide) family. Two bioactive
      forms, PACAP38 and PACAP27, a shorter N-terminal amidated peptide of PACAP38,
      have been identified. In this study, we explored the action of PACAP27 in rat
      dispersed pancreatic acini and the characteristics of its binding sites. PACAP27
      stimulated amylase secretion and intracellular cAMP production in a dose
      dependent manner. Adding 0.5 mM IBMX increased the potency of PACAP27 on the
      amylase secretion, but did not change the efficacy. The biological action of
      PACAP27 was mediated via intracellular cAMP as is also the case with PACAP38 or
      VIP. The time course study, however, revealed that PACAP stimulated the initial
      amylase secretion greater than VIP, suggesting an involvement of mechanisms other
      than intracellular cAMP. Binding studies using 125I-PACAP27 and 125I-VIP
      indicated that the binding sites for PACAP27 interacted with PACAP27 and VIP with
      a similar affinity. These observations suggested the presence of type II PACAP
      binding sites in the normal acini of the rat pancreas which may be functionally
      coupled with acinar enzyme secretion.

PMID- 7512759
TI  - Anion pores from magainins and related defensive peptides.
AB  - The conformations and properties of magainins, powerful antimicrobial peptides
      isolated from Xenopus laevis skin, are reviewed. Although some emphasis will be
      placed upon membrane interactions both in living cells and liposomes, we will
      especially focus on pore-forming properties as studied with conductance
      measurements on doped planar lipid bilayers. The relevance to channel modelling
      and engineering will be stressed and finally the relations, analogies and
      differences, of magainins with other insect and mammalian defensive peptides,
      such as cecropins and defensins, will be presented.

PMID- 7512760
TI  - The cytolytic toxin aerolysin: from the soluble form to the transmembrane
      channel.
AB  - Aerolysin is a cytolytic toxin which forms channels in the plasma membranes of
      eucaryotic cells. The protein is secreted by Aeromonas hydrophila as an inactive
      protoxin. Its stability and water solubility are conferred by its ability to
      dimerize. Maturation of the protein occurs through proteolytic removal of a C
      terminal peptide outside the secreting cell. Although the aerolysin which is so
      produced is still a dimer, it then has the ability to oligomerize. The oligomer
      is the active form of the toxin, capable of forming the transmembrane channels
      that disrupt cells. We review here the present knowledge about the structure of
      aerolysin in relation to the various steps in channel formation.

PMID- 7512761
TI  - Mechanism of action of equinatoxin II, a cytolysin from the sea anemone Actinia
      equina L. belonging to the family of actinoporins.
AB  - Actinia equina equinatoxin II (EqT-II) is a representative of a family of pore
      forming, basic, polypeptide toxins from sea anemones, now called actinoporins.
      This family comprises at least 27 members, which are all hemolytic at rather low
      concentrations. Red blood cell (RBC) hemolysis by EqT-II is the result of a
      colloid-osmotic shock caused by the opening of toxin-induced pores. Using osmotic
      protectants of different size the functional radius of the lesion was estimated
      to be approximately 1.1 nm. These pores are most probably constituted by
      oligomeric aggregates of cytolysin molecules, whose presence on the membrane of
      lysed RBC was directly demonstrated by polyacrylamide gel electrophoresis (PAGE)
      after covalent cross-linking. EqT-II is active also against a variety of
      mammalian cells including leukocytes, platelets and cardiomiocytes. An increased
      permeability of the plasma membrane after Eq-II attack is compatible with the
      notion that the toxin forms pores also on these cells. Eq-II permeabilises even
      purely lipidic model membranes, suggesting a protein receptor is not necessary.
      Using calcein-loaded unilamellar vesicles (UVs) comprised of phosphatydylcholine
      (PC) mixed with other lipids we observed that the rate and extent of
      permeabilization greatly increases when sphingomyelin (SM) or the ganglioside GM1
      were introduced, particularly in the case of large UVs (which are more sensitive
      to the toxin than small UVs). PAGE indicated that the increased effect of Eq-II
      on SM containing vesicles is due to an increased level of toxin binding to such
      vesicles. The formation of cation-selective channels by EqT-II was directly
      demonstrated using planar lipid membranes where the toxin induced discrete
      increases of the film conductivity. The conductance of the channel was consistent
      with the estimated size of the lesion formed in RBC. Several factors can affect
      toxin activity: serum, low pH, low ionic strength and multivalent cations are
      potent inhibitors. pH Dependence is bell shaped, optimum activity being between
      pH 8 and 9. Similarly the action of Ca2+ is also bivalent: up to a concentration
      of approximately 2 mM it stimulates hemolysis, but above this concentration it
      inhibits (with 50% inhibition occurring at approximately 10 mM). When the known
      amino acid sequences of actinoporins are examined a common trait emerges; the
      presence of a well conserved, amphiphilic, putative alpha-helix at the N
      terminus, which might be involved in the insertion of EqT-II in lipid membranes.

PMID- 7512762
TI  - The channel formed in planar lipid bilayers by the protective antigen component
      of anthrax toxin.
AB  - Anthrax toxin consists of three proteins: edema factor (EF, 89 kDa), lethal
      factor (LF, 90 kDa), and protective antigen (PA, 83 kDa). The former two gain
      access to the cytosol, where they exert their respective toxic effects on a cell,
      only in binary combination with PA. The proposed pathways of EF and LF transport
      consists of (i) PA attaching to a membrane receptor; (ii) its proteolytic
      cleavage into two fragments, of which the larger, 63 kDa piece (PA63) remains
      attached to the receptor; (iii) either EF or LF binding to PA63; (iv) the complex
      undergoing endocytosis, and EF or LF being translocated into the cytosol from an
      acidic vesicle compartment. In planar phospholipid bilayers, PA63 (but not whole
      PA) forms cation-selection channels; the channel-forming activity of PA63
      dramatically increases when the pH of the solution to which it was added is
      lowered. Tetraalkylammonium ions block the PA63 channel by binding to a site
      within the channel lumen. Analysis of this blocking phenomenon reveals that these
      ions can pass through the channel from one side of the membrane to the other and
      that the diameter of the channel is about 12 A. The N-terminal 30 kDa end of EF,
      which contains the region of EF that binds to PA63, interacts with the PA63
      channel in a voltage-dependent manner. The nature of the voltage-gating suggests
      that this binding fragment of EF can enter and block the channel and even pass
      through it, but further evidence will be required to establish this.

PMID- 7512763
TI  - The pore-forming peptide of Entamoeba histolytica, the protozoan parasite causing
      human amoebiasis.
AB  - Amoebapore, the pore-forming peptide of E. histolytica has been isolated and its
      structure elucidated on the cDNA and protein level. The peptide is composed of 77
      amino acid residues including six cysteine residues and has a molecular mass of
      8244 Da. The primary translation product contains a signal sequence of 21 mostly
      hydrophobic amino acid residues. The active peptide has been located in the
      cytoplasmic granules of the amoebae. Circular dichroism spectroscopy revealed an
      all alpha-helical conformation and computer-aided secondary structure prediction
      yielded a structure of four helices. The helical conformation and three
      intramolecular disulfide bonds impart a highly compact and rigid structure upon
      the molecule. The activity of amoebapore, measured by a liposome depolarization
      assay, is resistant to heating at 100 degrees C in the absence of reducing
      agents. Synthetic peptides corresponding to the helices 1 and 3 exhibited pore
      forming activity. Two minor, biologically active isoforms of amoebapore have
      amino acid sequence identity of 57% and 47%, respectively. Whereas amoebapore is
      a constituent of pathogenic E. histolytica isolates, nonpathogenic E. histolytica
      produce a structurally very similar peptide, the specific activity of which is
      approximately one third that of amoebapore. The biological significance of
      amoebapore for the pathogenicity of E. histolytica and specifically for its
      cytolytic activity remains to be determined.

PMID- 7512765
TI  - Microglia emerge from the fog.

PMID- 7512764
TI  - Nitric oxide synthase inhibition reduces caudate injury following transient focal
      ischemia in cats.
AB  - BACKGROUND AND PURPOSE: We tested the hypothesis that inhibiting nitric oxide
      production either before or during transient focal ischemia affects early
      postischemic brain injury. METHODS: Halothane-anesthetized cats underwent 1 hour
      of left middle cerebral artery occlusion plus 3 hours of reperfusion.
      Pretreatment groups received either intravenous N omega-nitro-L-arginine methyl
      ester (L-NAME; 10 mg/kg, n = 10) or an equal volume of diluent (10 mL saline, n =
      10) over 30 minutes before ischemia. Posttreatment groups received intravenous L
      NAME (10 mg/kg) over 30 minutes from 45 minutes of ischemia to 15 minutes of
      reperfusion (n = 10) or intravenous L-NAME (10 mg/kg) plus L-arginine (200 mg/kg)
      over the same period followed by continuous L-arginine infusion (200 mg/kg per
      hour) for the remainder of reperfusion (n = 10). RESULTS: Microsphere-determined
      blood flow to ipsilateral caudate nucleus and inferior temporal cortex decreased
      to the same extent during ischemia and recovered to the same extent during
      reperfusion in the four groups. Triphenyltetrazolium-determined injury volume of
      ipsilateral caudate nucleus in cats treated with L-NAME before or during ischemia
      (42 +/- 7% and 42 +/- 3% of caudate nucleus, respectively; mean +/- SE) was less
      (P < .05) compared with that in cats pretreated with saline (72 +/- 5%) or cats
      treated with L-NAME plus L-arginine (68 +/- 5%). Ipsilateral cerebral hemispheric
      injury volume was similar among the four groups (23 +/- 5%, 13 +/- 3%, 18 +/- 5%,
      and 29 +/- 5% of hemisphere in groups treated with L-NAME before ischemia and
      during ischemia, the saline-treated group, and the group treated with L-NAME plus
      L-arginine, respectively). CONCLUSIONS: Inhibition of nitric oxide synthase
      decreases caudate injury volume from transient focal cerebral ischemia in cats.
      The beneficial effect is reversed by L-arginine and is not caused by favorable
      redistribution of blood flow during ischemia and reperfusion. Because L-NAME was
      efficacious when administered at reperfusion, nitric oxide generated during
      reperfusion appears to contribute to caudate injury.

PMID- 7512766
TI  - D2 receptor genes--the cause or consequence of substance abuse?

PMID- 7512767
TI  - On neuronal ill health.

PMID- 7512768
TI  - The specificity of the 'nonspecific' midline and intralaminar thalamic nuclei.
AB  - The midline and intralaminar thalamic nuclei have long been considered to be a
      'nonspecific' nuclear complex that relays the activity of the brain-stem
      reticular formation to widespread cerebral-cortical areas. Over the past decade,
      it has become clear that individual midline and intralaminar nuclei each receive
      specific sets of afferents and project to specific parts of the cerebral cortex
      and striatum. Moreover, the targets of the thalamocortical and thalamostriatal
      projections of a given nucleus are interconnected through corticostriatal
      projections. Therefore, the midline and intralaminar nuclei might have a dual
      role in corticosubcortical interactions in the forebrain. Through distinct sets
      of inputs to individual midline or intralaminar thalamic nuclei, these nuclei are
      in a position to interact selectively with particular, functionally segregated
      basal-ganglia-thalamocortical circuits. By way of nonselective inputs, in
      particular from cholinergic brain-stem nuclei, the midline and intralaminar
      nuclei might act in concert to modify the level of activity of the entire basal
      ganglia-thalamocortical system.

PMID- 7512769
TI  - Bimodal gating of the Na+ channel.
AB  - Inactivation of voltage-gated ion channels, whether they are selective for Na+,
      K+ or Ca2+, probably never involves their total closure, and some flow of ion
      current persists if large enough test pulses are applied. Incomplete inactivation
      was first reported for the Na+ channels of the squid giant axon, but has since
      been observed in other types of peripheral nerve and, more recently, in muscle
      fibres and the neurons of mammalian brain. The phenomenon is therefore widespread
      and has important implications for the functioning of voltage-gated channels in a
      variety of situations. It is best described in terms of a gating mechanism that
      switches the channel from an initial mode in which it has a high probability of
      opening to one in which the probability is greatly lowered, but not reduced to
      zero.

PMID- 7512770
TI  - Chemosensory transduction in eukaryotic microorganisms: trends for neuroscience?
AB  - It might appear curious to read about yeast, slime molds and protozoa in a
      journal dedicated to neuroscience. However, despite their distinct lack of
      synapses, eukaryotic microorganisms hold a wealth of information relevant to the
      signal-transduction pathways that underly activity in neuronal receptor cells,
      particularly those subserving the chemical senses. Microorganisms are sensitive
      to chemical stimuli from their environment and thus have similarities to receptor
      neurons of the olfactory system and the taste bud. Here, we introduce receptors,
      second messengers and effectors responsible for chemosensory signal transduction
      in yeast mating, sea-urchin spermatozoan chemotaxis, slime-mold aggregation and
      development, and ciliate chemoresponses.

PMID- 7512771
TI  - Targeting learning.
AB  - Novel transgenic approaches provide an exciting opportunity to assess the impact
      of the loss of specific genes in the biochemistry and electrophysiology of
      neurons involved in a learned behavior. Recent studies describing mice harboring
      mutations in five kinase genes expressed in the hippocampus found that two of
      these kinases, the alpha-Ca(2+)-calmodulin-dependent kinase II and the Fyn
      tyrosine kinase are necessary for the establishment of long-term potentiation. In
      addition to providing a new tool for the dissection of the molecular mechanisms
      of synaptic plasticity, these mutants will be important in determining how
      changes in synaptic strength affect not only learning and memory, but also a host
      of other processes thought to be associated with plasticity.

PMID- 7512772
TI  - Attentional networks.
AB  - Recent brain-imaging and neurophysiological data indicate that attention is
      neither a property of a single brain area, nor of the entire brain. While
      attentional effects seem mediated by a relative amplification of blood flow and
      electrical activity in the cortical areas processing the attended computation,
      the details of how this is done through enhancement of attended or suppression of
      unattended items, or both, appear to depend on the task and brain-area studied.
      The origins of these amplification effects are to be found in specialized
      cortical areas of the frontal and parietal lobes that have been described as the
      anterior and posterior attention systems. These results represent substantial
      progress in the effort to determine how brain activity is regulated through
      attention. While many philosophical and practical issues remain in developing an
      understanding of attentional regulation, the new tools available should provide
      the basis for progress.

PMID- 7512773
TI  - Corticotropin-releasing factor and neuropeptide Y: role in emotional integration.
AB  - The amygdala complex integrates stressful stimuli and is critical in transducing
      their aversive value into autonomic, endocrine and behavioural responses.
      Stimulation within the amygdala complex produces signs of fear without a relevant
      external object, while lesions in this region abolish normal fear responses. In a
      manner characteristic of phylogenetically old limbic brain areas, the complex
      neurochemical anatomy of the amygdala involves a large number of phylogenetically
      old peptide mediators. The distribution and connectivity of these peptide systems
      have been extensively studied, but less is known about their functional role.
      Recent evidence suggests that two neuropeptides, corticotropin-releasing factor
      (CRF) and neuropeptide Y (NPY) exert a reciprocal regulation of responsiveness to
      stressful stimuli, possibly via an interaction of these two systems in the
      amygdala.

PMID- 7512774
TI  - [Treatment problems in patients with prostatic adenoma].
AB  - The authors review treatment results for 947 patients with prostatic adenoma. The
      physicians used transvesical methods. Whatever its modification, transvesical
      adenomectomy performed endourethrally fails to bring good responses. The
      proportion of the complications remains great: urethral stricture 5.9%, cervical
      bladder stenosis 3.03%, enuresis 2.6%. In view of this, a method of transvesical
      adenomectomy performed extraurethrally is proposed. The technique implies
      application of special circular scalpel enabling the surgeon to dissect
      adenomatous nodules from prostatic urethra without its injury. The procedure
      produced good results in 32 patients with prostatic adenoma.

PMID- 7512775
TI  - [A method for hemostasis in transvesical adenomectomy].
AB  - The hemostatic techniques proposed by the authors in transvesical adenomectomy
      implies U-form replaceable catgut ligatures placed with circular capture of the
      cervix vesicae and prostate capsule followed by their urethral stretching out.
      The technique is applicable in different adenoma sizes, prostate and cervix
      vesicae sclerosis. The procedure was used in 112 cases. Blood loss measured in 54
      patients averaged 160 ml which is less than under other techniques of
      adenomectomy. Postoperative hemorrhage was observed in 1 patient (0.9%).
      Lethality was 1.8%. Long-term postoperative infectious complications occurred in
      4.5%, organic ones (bladder cervical stricture) in 1.8% of the examinees. The
      technique is recommended for introduction into clinical practice as simple to
      perform, warranting reliable hemostasis and reduced intraoperative bleeding.

PMID- 7512776
TI  - Steady state feedback in mammalian phototransduction illustrated by a nomogram.
AB  - Published data characterizing the four reactions responsible for the Ca(2+)
      mediated negative feedback in mammalian rod phototransduction were used to
      generate graphs which are combined in a circular fashion so that the y-axis of
      one serves as the x-axis of the next. The nomogram thus created makes it possible
      to determine by inspection the steady state situation in darkness, and the quasi
      steady state situations that pertain shortly after exposure to light of different
      intensities. The results predicted by the nomogram suggest that Ca(2+)-mediated
      negative feedback is responsible for the Weber-Fechner relationship between
      stimulus and response.

PMID- 7512777
TI  - [Status of nucleic acid and total protein synthesis in hematopoietic organs in
      mice with alloxan diabetes].
AB  - Rates of 3H-thymidine, 3H-uridine and 14C-glycine incorporation in nucleic acids
      and total proteins were studied in cells of bone marrow, spleen, thymus and
      ileocecal lymph nodes tissues of BALB/c mice with subacute alloxan diabetes
      (content of blood sugar was higher than 14 mmol/l). Synthesis of DNA, RNA and
      protein was not considerably inhibited in the thymus tissue of the impaired
      animals which may correlate with pronounced dysfunction of cytotoxic T
      lymphocytes typical for the disease.

PMID- 7512779
TI  - Management of benign prostatic hyperplasia.
AB  - The Council on Scientific Affairs of the California Medical Association presents
      the following inventory of items of progress in urology. Each item, in the
      judgment of a panel of knowledgeable physicians, has recently become reasonably
      firmly established, both as to scientific fact and important clinical
      significance. The items are presented in simple epitome, and an authoritative
      reference, both to the item itself and to the subject as a whole, is generally
      given for those who may be unfamiliar with a particular item. The purpose is to
      assist busy practitioners, students, researchers, and scholars to stay abreast of
      these items of progress in urology that have recently achieved a substantial
      degree of authoritative acceptance, whether in their own field of special
      interest or another. The items of progress listed below were selected by the
      Advisory Panel to the Section on Urology of the California Medical Association,
      and the summaries were prepared under its direction.

PMID- 7512780
TI  - Prostate-specific antigen in screening for prostate cancer.

PMID- 7512778
TI  - Evidence for hepatitis C viral infection in patients with primary hepatocellular
      carcinoma.
AB  - In testing for antibodies to the hepatitis C virus (anti-HCV) in 112 patients
      with primary hepatocellular carcinoma, 10 of 33 white patients (30%) and 15 of 79
      Asian patients (19%) had a positive response to the antibody. The antibody
      profile to individual hepatitis C viral antigens and the presence of circulating
      hepatitis C viral RNA were determined in the 25 patients. The anti-HCV antibodies
      most frequently detected were toward the antigens from the core (C22) and NS3
      regions. Serum hepatitis C viral RNA was present in 17 of the 25 patients (68%),
      and these patients tended to have serum levels of alanine and aspartate
      aminotransferases higher than those patients without viremia (136 +/- 22 U per
      liter versus 64 +/- 11 U per liter and 161 +/- 26 U per liter versus 79 +/- 14 U
      per liter, respectively, both P < .05). Of the 15 Asian patients with
      hepatocellular carcinoma and anti-HCV, 4 (27%) had coexisting hepatitis B surface
      antigen (HBsAg) and 13 (87%) had antibodies to either hepatitis B core or surface
      antigen. Of the 10 white patients with anti-HCV, however, only 1 (10%) had
      hepatitis B virus antibodies (P < .01). Among 4 Asian patients with coexisting
      anti-HCV and HBsAg, 1 was found to have serum hepatitis B viral DNA and the other
      3 had hepatitis C viral RNA. A history of blood transfusion was obtained from 12
      of the 25 patients with anti-HCV (48%); 20 (80%) had coexisting cirrhosis. Our
      findings support the hypothesis that hepatitis C virus is an important etiologic
      agent in the development of primary hepatocellular carcinoma in both white and
      Asian patients in the United States.

PMID- 7512781
TI  - [Dopamine antibodies in parkinsonism patients and their possible role in the
      pathogenesis of the parkinsonian syndrome].
AB  - Dopamine antibodies (DAb) were found in the blood serum of parkinsonian patients,
      middle-aged and elderly, but not young. There was a correlation between the DAb
      incidence and dominant symptom in the middle-aged and elderly patients and
      between DAb and anginal parkinsonism in the elderly patients. DAb-binding serum
      gamma-globulins of parkinsonian patients injected into rat caudate nuclei induced
      the pathogenetic mechanism of Parkinson's syndrome (the generator of
      pathologically enhanced excitation-GPEE) in this brain part and evoked main
      parkinsonian symptoms (oligokinesia, rigidity and tremor). This effect was more
      expressed in the elderly rats compared with the young animals. The DAb role in
      the Parkinson's syndrome pathogenesis and in L-DOPA therapeutic tolerance
      formation is discussed.

PMID- 7512783
TI  - Urticaria from erythromycin.
AB  - We report an adverse cutaneous reaction (urticaria) due to erythromycin. A
      positive skin prick and leukocyte histamine release tests, as well as a positive
      single-blind, placebo controlled oral challenge to erythromycin, strongly suggest
      an IgE mediated hypersensitivity mechanism.

PMID- 7512782
TI  - Rupture of pregnant rudimentary uterine horn with fetal salvage.
AB  - Pregnancy in a rudimentary uterine horn is rare and is usually associated with
      fetal death and serious maternal morbidity or mortality. A case is presented of
      such a pregnancy associated with a high maternal serum alpha feto-protein
      presenting as an acute emergency at 29 weeks' gestation resulting in fetal
      salvage.

PMID- 7512784
TI  - Antiarrhythmic drugs: how to evaluate them?
AB  - For two decades, the evaluation of antiarrhythmic drugs has essentially been
      based on the count of premature beats during Holter monitoring and the
      inducibility of tachyarrhythmias during electrophysiologic studies. These
      approaches are convenient to provide firmly established short-term evaluations of
      the effects of type I agents in relatively benign arrhythmias occurring in
      patients with good cardiac function. However, the situation is much more
      uncertain for long-term outcome in serious tachyarrhythmias occurring in severely
      diseased patients with an altered myocardium. In addition, indications for type I
      agents are not really adapted to beta-blockers and type III drugs, the effects of
      which are much more difficult to assess and depend at least in part on the target
      arrhythmia. There is an interest in evaluating drug efficacy in terms of
      responders and nonresponders and in understanding the reasons for a response
      rather than reliance on pure quantitative data, the meaning of which may be less
      relevant in the final analysis. We must also recognize the need to reconcile the
      multiple obstacles encountered when severely diseased patients must be managed
      efficaciously and safely in the long term with new drugs, the effects of which
      need objective assessment.

PMID- 7512785
TI  - CD34 immunostaining of bone marrow biopsy specimens is a reliable way to classify
      the phases of chronic myeloid leukemia.
AB  - Flow cytometry studies have shown that high expression of CD34 antigen in
      patients with chronic myeloid leukemia (CML) is indicative of accelerated or
      blastic phases. It has also been suggested that similar information can be
      obtained by CD34 immunostaining of bone marrow biopsy specimens. To test this
      hypothesis, the authors studied 59 conventionally fixed, paraffin-embedded bone
      marrow trephine biopsy specimens, representing the three phases of the disease
      (stable, accelerated, and blast crisis). Immunohistochemical staining for CD34
      was performed using QBEnd10, a monoclonal antibody reactive in routine paraffin
      embedded tissue. The differences in CD34 positivity among chronic, accelerated,
      and blastic phases of CML were highly significant (P = .0001). This study
      demonstrated that CD34 immunohistochemical staining of bone marrow biopsy
      specimens represents a reliable method for classifying patients with CML and may
      provide essential diagnostic and prognostic information when a marrow aspirate is
      unavailable.

PMID- 7512786
TI  - Detection of Mycobacterium avium-intracellulare complex in bone marrow specimens
      of patients with acquired immunodeficiency syndrome.
AB  - Thirty-seven bone marrow core biopsy specimens from 21 human immunodeficiency
      virus-infected patients with Mycobacterium avium-intracellulare complex
      bacteremia were stained using rabbit polyclonal antibodies against Mycobacterium
      bovis strain Bacillus-Calmette-Guerin (BCG) and Mycobacterium duvalii, as well as
      Kenyon and Fite stains, to compare sensitivities of these techniques and evaluate
      possible response to therapy. The patients in this study had participated in a
      phase I/II trial of liposome-encapsulated gentamicin therapy. Two biopsy
      specimens had inadequate tissue for evaluation. Thirty-two specimens demonstrated
      bacilli with anti-M duvalii, 33 with anti-BCG, 20 with Kenyon, and 23 with Fite.
      Two were negative with all stains. Fifteen biopsy specimens had epithelioid
      granulomas, 12 had histiocytic granulomas, and 1 had a granuloma of indeterminate
      type. The remaining seven biopsy specimens had no granulomas. Four of these seven
      demonstrated bacilli with anti-M duvalii, 5 with anti-BCG, 1 with Kenyon, and 2
      with Fite. The number of M avium-intracellulare organisms per milliliter of blood
      decreased in 14 of 21 patients after liposome-encapsulated gentamicin therapy.
      However, none of the 11 patients whose pre- and post-therapy bone marrow core
      biopsy specimens were both evaluable demonstrated a reduction in the number of M
      avium-intracellulare organisms. The authors concluded that anti-M duvalii and
      anti-BCG are more sensitive than acid-fast stains for identifying M avium
      intracellulare infection in bone marrow core biopsy specimens of patients who
      have acquired immunodeficiency syndrome (AIDS) with M avium-intracellulare
      bacteremia. Bone marrow core biopsy specimens may provide a perspective on M
      avium-intracellulare infection in AIDS patients that differs from the one
      provided by blood cultures.

PMID- 7512787
TI  - Invasive squamous cell carcinoma and cervical intraepithelial neoplasia III of
      uterine cervix. Morphologic differences other than stromal invasion.
AB  - The authors compared 69 cases of surgically proven invasive squamous cell
      carcinoma (ISCC) of uterine cervix with 48 cone biopsy specimens that showed
      cervical intraepithelial neoplasia (CIN) grade III. Histologic features that were
      preferentially associated with ISCC included the following: giant bizarre cells
      (66.7% in ISCC, 6.26% in CIN III, P < .01); large keratinized cells (87% in ISCC,
      0% in CIN III, P < .01); keratin pearls (40.6% in ISCC, 0% in CIN III, P < .01);
      necrosis (79.7% in ISCC, 8.3% in CIN III, P < .01); and neovascularization (56.5%
      in ISCC, 0% in CIN III). In 51 (74%) cases of ISCC, a CIN III component was
      present, of which 18 (35.3%) showed large keratinized cells or keratin pearls in
      the in situ components. None of the CIN III cases showed more than one of the
      above features. In the ISCC group, the above features occurred with similar
      frequency in microinvasive and frankly invasive tumors. The authors' results
      agree with previous Papanicolaou-smear cytologic studies, which found that ISCC
      can be distinguished accurately from CIN III by the morphology of the neoplasm.
      The authors concluded that cervical biopsy specimens that show two or more of the
      above features are highly suggestive of ISCC, even when stromal tissue is absent
      or insufficient for the assessment of invasion. Furthermore, in cervical biopsy
      specimens showing CIN III, the presence of large keratinized cells or keratin
      pearls may signify the presence of invasive lesions elsewhere in the cervical
      mucosa.

PMID- 7512788
TI  - Identification of a small supernumerary ring chromosome 8 by fluorescent in situ
      hybridization in a child with developmental delay and minor anomalies.
AB  - We report a 15-month-old female with developmental delay, hypotonia, and minor
      anomalies whose karyotype is 47,XX,+r. Due to its small size, the origin of the
      ring chromosome was indeterminate by standard G-banded karyotyping. Fluorescent
      in situ hybridization was performed, which indicated that the ring chromosome was
      derived from the pericentric region of chromosome 8.

PMID- 7512789
TI  - Hypoplasia of the cerebellar vermis and corpus callosum in thrombocytopenia with
      absent radius syndrome on MRI studies.
AB  - Thrombocytopenia with absent radius (TAR) syndrome is infrequently (7%)
      associated with mental retardation. In those cases, the mental deficiency is
      presumed to be a consequence of intracranial hemorrhage due to the
      thrombocytopenia. We report on 2 infants with TAR syndrome. One had developmental
      delay with evidence of cerebral dysgenesis by magnetic resonance imaging (MRI).
      Such findings have not been noted in the literature, but may not have been
      investigated in most cases. The other infant with TAR syndrome, who has had
      normal psychomotor development, has a normal brain on MRI scan. Detailed
      neuroimaging studies, preferably MRI, should be considered in the evaluation of
      patients with TAR syndrome, especially when there are documented signs of
      developmental delay, with or without a history of intracranial hemorrhage.

PMID- 7512790
TI  - Amyloid beta precursor protein and ubiquitin epitopes in human and experimental
      dystrophic axons. Ultrastructural localization.
AB  - Dystrophic axons (DA) represent a major pathological feature of several
      neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and
      Alzheimer disease. We have previously presented evidence that amyloid beta
      precursor protein (BPP) and ubiquitin (Ub) are present in DA of different origin.
      We have now characterized the immunoreactivity of DA experimentally induced in
      rat by the administration of parabromophenylacetylurea (BPAU) and examined the
      subcellular localization of Ub and BPP in BPAU-induced DA and in DA present in
      subjects affected by INAD. BPAU-induced DA strongly immunoreacted with antisera
      to Ub and to COOH- and NH2-terminal regions of BPP. Immunoblots of DA-enriched
      brain regions were consistent with an increase in the amount of Ub and BPP in DA.
      Moreover, BPAU-induced DA immunoreacted with antibodies to PGP 9.5, a neuronal
      specific Ub COOH-terminal hydrolase, and to the inducible heat shock protein 70.
      Antigenic characterization also indicated that the tubulovesicular membranes
      within DA derived largely from the smooth endoplasmic reticulum rather than from
      the Golgi system or the synaptic vesicles. Subcellular immunolocalization of Ub
      and BPP in both INAD- and BPAU-induced DA revealed that Ub and BPP colocalize in
      granulovesicular material in both conditions. In INAD DA intense Ub
      immunoreactivity was also detected in nonmembranous electron dense structures
      that were present only in these DA, probably because of the chronic course of
      INAD. Although BPP immunostaining may be related to accumulation of BPP
      containing membranes in DA, Ub immunostaining is likely to result from activation
      of the Ub system by the neuron in the attempt to remove excessive and possibly
      abnormal proteins. A similar pathogenesis can be postulated for DA of Alzheimer
      disease.

PMID- 7512791
TI  - Androgen receptor status in localized and locally progressive hormone refractory
      human prostate cancer.
AB  - Heterogeneity in human androgen receptor (hAR) expression in prostate cancer is
      considered to be implicated in tumor progression. hAR expression was therefore
      studied immunohistochemically in localized and locally progressive, hormone
      refractory (HR) prostate cancer. Because altered functional activity of the hAR
      may be due to changes in the structural integrity of the hAR gene, exons 2 to 8
      of the hAR gene were assessed for mutations by single-strand conformation
      polymorphism (SSCP) analysis and exon 1 was analyzed for the size of the CAG
      repeat. The hormone binding capacity, a prerequisite for ligand-regulated
      receptor function, was determined by a ligand binding assay. Coexpression of the
      hAR and prostate-specific antigen (PSA) was studied by a sequential double
      immunoenzymatic staining to verify whether PSA expression is a parameter of hAR
      function. Almost all human prostatic carcinomas revealed heterogeneous hAR
      expression, regardless of tumor differentiation and progression. Putative
      predominance of hAR-negative tumor areas in HR prostate cancer was not observed.
      No hAR gene mutations or major changes in the CAG repeat were found in the 18 HR
      carcinomas or in the 9 control samples. Moreover, all selected hAR-expressing
      cancers were able to bind the synthetic androgen methyltrienolone (R1881).
      Immunoenzymatic double staining revealed even PSA expression in hAR-negative
      tumor areas. PSA immunohistochemistry in human prostatic carcinomas therefore is
      of no use in determining hAR functional activity. Thus, most prostatic
      carcinomas, even when progressed to a state of hormone insensitivity, contain a
      structurally intact hAR gene, heterogeneously expressed with retained androgen
      binding capacity.

PMID- 7512792
TI  - Loss of co-localization of alpha 6 beta 4 integrin and collagen VII in bladder
      cancer.
AB  - In normal epithelial cells, the alpha 6 beta 4 integrin co-localizes with the
      hemidesmosomal anchoring complex on the basolateral surface of basal cells. We
      studied the co-expression of alpha 6 beta 4 integrin with collagen VII, a
      component of the hemidesmosomal anchoring complex, in normal bladder tissues and
      in bladder cancers. In normal bladder, the alpha 6 beta 4 integrin co-localized
      with collagen VII at the junction of the basolateral surface of the basal
      urothelial cells and the lamina propria. In five of six noninvasive bladder
      cancers, the localization of collagen VII remained unchanged, found at the
      junction of the basal cells and the papillary connective tissue. However, in
      these tumors the alpha 6 beta 4 expression was not polarized and was expressed on
      suprabasal as well as basal cells. In invasive bladder cancers, the majority (25
      of 30) showed either loss of alpha 6 beta 4 and/or collagen VII expression or
      showed a lack of co-localization of alpha 6 beta 4 and collagen VII. Our results
      show derangement of the co-localization of these two components of the
      hemidesmosomal anchoring complex is a consistent event in bladder cancer.
      Furthermore, the degree of derangement increases in invasive cancers. Loss of co
      expression and co-localization of alpha 6 beta 4 and collagen VII may predispose
      cancer cells to local invasion and may facilitate metastasis as well.

PMID- 7512794
TI  - Nitric oxide synthase inhibition attenuates hypoglycemic cerebral hyperemia in
      piglets.
AB  - We tested the hypothesis that nitric oxide (NO) mediates hypoglycemia-induced
      cerebral vasodilation in piglets. Piglets (1-2 wk old) were made hypoglycemic
      with insulin (200 U/kg i.v.) with and without an NO synthase inhibitor, N omega
      nitro-L-arginine methyl ester (L-NAME, 40 mg/kg i.v.). Electroencephalogram
      (EEG), cerebral O2 consumption (CMRO2), and cerebral blood flow (CBF) were
      measured before L-NAME and insulin and for 180 min after insulin. Hypoglycemia
      led to isoelectric EEG earlier after L-NAME (87 +/- 8 min) than without L-NAME
      pretreatment (132 +/- 13 min). CBF increased in all brain regions during
      hypoglycemia at the onset of isoelectric EEG and was associated with increased
      CMRO2.L-NAME prevented the increase in CMRO2 and attenuated vasodilation in
      forebrain (154 +/- 37 vs. 400 +/- 60%), cerebellum (251 +/- 52 vs. 386 +/- 52%),
      and cortical gray matter (183 +/- 47 vs. 524 +/- 93%) but had no effect on CBF
      responses in brain stem, thalamus, caudate, or hippocampus. We conclude that NO
      or a NO-containing compound mediates cerebral vasodilation induced by profound
      insulin-hypoglycemia in piglets and that this vasodilation plays an important
      role in the adaptation of immature brain to hypoglycemia.

PMID- 7512793
TI  - Aberrant production of interleukin-8 and thrombospondin-1 by psoriatic
      keratinocytes mediates angiogenesis.
AB  - Psoriasis is a common inherited skin disease that is characterized by
      hyperproliferation of epidermal keratinocytes and excessive dermal angiogenesis.
      A growing body of evidence supports a key pathogenetic role for activated
      keratinocytes in the angiogenic response that accompanies psoriasis. We
      investigated the role of psoriatic epidermis in the aberrant expression of
      angiogenesis by examining the ability of pure populations of multipassaged
      keratinocytes obtained from the skin of normal individuals and psoriatic patients
      to induce angiogenesis in vivo in the rat corneal bioassay and endothelial cell
      chemotaxis in vitro. Media conditioned by keratinocytes from psoriatic patients,
      including both symptomless skin and psoriatic plaques, induced vigorous
      angiogenic responses in over 90% of corneas tested and potently stimulated
      directional migration of capillary endothelial cells in vitro. In contrast,
      conditioned medium from normal keratinocyte cultures was weakly positive in less
      than 10% of corneas assayed and failed to stimulate endothelial cell chemotaxis.
      Furthermore, keratinocytes from psoriatic skin exhibited a 10- to 20-fold
      increase in interleukin-8 production and a seven-fold reduction in thrombospondin
      1 production. The angiogenic activity present in keratinocyte-conditioned media
      from psoriatic patients was suppressed by adding either highly purified
      thrombospondin-1 (125 ng) or following the addition of either normal keratinocyte
      conditioned media or neutralizing interleukin-8 antibody. We conclude that
      psoriatic keratinocytes are phenotypically different from normal keratinocytes
      with respect to their angiogenic capacity and that this aberrant phenotype is
      attributable to a defect in the overproduction of interleukin-8 and a deficiency
      in the production of the angiogenesis inhibitor thrombospondin-1.

PMID- 7512795
TI  - Calcitonin gene-related peptide promotes cerebrovascular dilation during cortical
      spreading depression in rabbits.
AB  - We examined the role of calcitonin gene-related peptide (CGRP) in cortical
      spreading depression (CSD)-induced dilation of rabbit pial arterioles. In urethan
      anesthetized rabbits instrumented with a closed cranial window, CSD induction
      with KCl dilated pial arterioles from 86 +/- 10 to 132 +/- 13 (mean +/- SE, n =
      6) microns (a 54 +/- 9% increase). Topical administration of 12.8 microM CGRP-(8
      37), a competitive inhibitor of the CGRP receptor, reduced CSD-induced pial
      dilation from 54 +/- 9% baseline to 33 +/- 9% (P < 0.05). Removal of the receptor
      antagonist from the brain surface restored CSD-induced dilation to 59 +/- 11% (P
      < 0.05, compared with the response with the antagonist present). In other
      animals, we showed that this dose of the CGRP antagonist attenuated arteriolar
      dilation to topically applied 10(-7) M CGRP (n = 5), but it did not alter
      arteriolar dilation to arterial hypercapnia. We also evaluated the dilator
      potency of substance P (SP) compared with CGRP. Dilation with 10(-7) M SP was
      only 22 +/- 11%, whereas arterioles dilated to 57 +/- 7% above baseline diameter
      with 10(-7) M CGRP. We conclude that CGRP contributes to the transient arteriolar
      dilation that is characteristic of CSD.

PMID- 7512796
TI  - Vasodilation induced by substance P in guinea pig carotid arteries.
AB  - In the guinea pig carotid artery with an intact endothelium, substance P (SP, 10(
      10)-10(-7) M) relaxed the norepinephrine- (NE) contracted smooth muscles
      transiently, in a concentration-dependent manner. Acetylcholine (ACh, 10(-6) M)
      produced a sustained relaxation. SP and ACh also relaxed muscles contracted with
      high-K (29.6 mM) solution, with a similar form but with a reduced amplitude
      compared with findings in NE-contracted muscles. In the presence of nitroarginine
      (10(-5) M) and NE, the ACh-induced relaxation was transient, with a reduced
      amplitude, whereas the SP-induced relaxation was not significantly changed. In
      muscles contracted with high-K solution containing nitroarginine, neither SP nor
      ACh produced relaxation. SP (> 10(-11) M) transiently hyperpolarized the
      membrane, but only when this peptide was applied from the intimal side of the
      intact vessel, and the peak amplitude reached approximately 20 mV from the
      resting potential at 10(-8) M. ACh transiently hyperpolarized the membrane (the
      peak amplitude being approximately 10 mV), in both the adventitial and intimal
      applications. In high-K solution, neither SP nor ACh produced hyperpolarization.
      The amplitude of hyperpolarizations produced by SP did not significantly change
      in the presence of nitroarginine, oxyhemoglobin, or indomethacin. Thus, SP
      induced relaxation seems to be produced mainly by endothelium-derived
      hyperpolarizing factor-induced hyperpolarization.

PMID- 7512797
TI  - Muscarinic receptor characterization in differentiating avian exocrine cells.
AB  - The type of muscarinic acetylcholine receptor in exocrine cells of the avian
      nasal gland in the undifferentiated quiescent (naive) stage and in the partly
      differentiated salt-secreting (stressed) stage was characterized by ligand
      binding experiments and by probing receptor messenger RNA with oligonucleotide
      probes specific for the mammalian receptor subtypes. Competition-binding studies
      using l-quinuclidinyl [phenyl-4-3H]benzilate and a series of other ligands
      indicated the presence of only one type of receptor in both cell types.
      Pharmacological characterization of its ligand-binding properties revealed
      similarities with the mammalian M3 type. However, 4-[[[(3
      chlorophenyl)amino]carbonyl]oxy]-N,N,N-trimethyl-2-butyn-1 - aminium chloride,
      generally a partial agonist in cells expressing mammalian M1 receptors, released
      calcium from intracellular stores in naive and stressed cells. To resolve this,
      we attempted to characterize the salt gland receptor by molecular means. Northern
      analysis of salt gland mRNA revealed weak signals only with oligonucleotide
      probes corresponding to the mammalian m1 receptor type. However, at higher
      stringencies these signals faded, indicating that the salt gland receptor may
      resemble the mammalian m1 subtype but has probably a considerable degree of
      sequence divergence. Such divergence may also explain the observed differences in
      pharmacological behavior between the avian and the mammalian glandular receptors.

PMID- 7512798
TI  - Desmoplastic malignant melanoma. An immunocytochemical study of 25 cases.
AB  - Using a panel of seven cell markers, we studied the value of immunocytochemical
      labelling in the histological diagnosis of desmoplastic malignant melanoma.
      Sections from routine formalin-fixed tissue of 45 surgical specimens were
      obtained from 25 cases of malignant melanoma that showed well-marked desmoplastic
      or neurotropic features. Routinely stained sections (Haematoxylin- and -eosin and
      melanin stains) were compared with the following panel of seven antibodies: S
      100, neuron-specific enolase (NSE), vimentin, factor XIIIa (FXIIIa), desmin and
      the newer, supposedly more specific antimelanoma antibodies HMB45 and NKIC3. S
      100 and NSE were the most sensitive antibodies for desmoplastic malignant
      melanoma with strong labelling of spindle cells in most cases. In contrast,
      results for NKIC3 were more variable; results were negative in nearly half the
      tumours, but strong labelling was seen in six cases (27%). Positive labelling for
      HMB45 was noted in five tumours (22%); it was mostly confined to small groups of
      cells in the superficial part of the lesions. Tumour spindle cells were negative
      for FXIIIa in all cases; there was no increase in the number of positive dermal
      dendritic cells compared to conventional and spindle cell melanoma. All tumours
      were desmin-negative, but most were vimentin-positive. Our findings indicate that
      immunocytochemistry is of less value in the diagnosis of desmoplastic malignant
      melanoma that it is with other types of malignant melanoma. However, positive or
      negative labelling for S-100 protein and NSE is useful for suggesting or
      excluding a diagnosis of desmoplastic malignant melanoma; neither marker is
      specific and, in particular, positive labelling is also found in most
      neurofibromas and benign cellular naevi.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512799
TI  - A controlled hematoxylin-eosin for actinic elastosis-lysis. Its versatility and
      use for vascular damage (actinic arteriopathy) in the skin and orbit.
AB  - To demonstrate elastic tissue and its reactions in the skin and other organs, the
      hematoxylin-eosin staining method had been modified in two ways: (a) the
      hematoxylin solution is used once only to obtain its full potential, and (b)
      aqueous eosin is given greater selectivity by controlling its pH with a buffer.
      This stain highlights the broad supporting role of elastic tissue, particularly
      in pressure-containing blood vessels. It also helps to define the hyperplasia,
      degeneration, and elastolysis that arise from its peculiar sensitivity to actinic
      radiation.

PMID- 7512803
TI  - Comparative analysis of neovascularization in primary cutaneous melanoma and
      Spitz nevus.
AB  - Spitz nevus is a well-known histologic simulator of malignant melanoma.
      Vascularity of human neoplasms has been associated with prognosis as well as
      propensity for metastasis. Were vascularity significantly different between
      melanoma and Spitz nevus, it could serve as a feature to distinguish between
      these two neoplasms. We evaluated the vascularity of a series of primary
      cutaneous melanomas ranging from thin superficial spreading to nodular lesions as
      well as superficial compound and nodular deep Spitz nevi by using light
      microscopic evaluation of factor-VIII-stained sections. Vascularity was density
      graded and microvessels were counted per x200 and x400 field. Vascular density
      and microvessel counts were significantly different between melanomas of 2+ and
      3+ vascularity compared with all types of Spitz nevi. Although nodular malignant
      melanomata tended to have a greater degree of vascularity than thin melanomas,
      there was a significant population of both of these subtypes having few or many
      vessels. We conclude that the number of microvessels per x200 and x400 field in
      areas of greatest vascularity is significantly less in Spitz nevus than in
      malignant melanoma. There is a subset of melanoma, however, in which the number
      of microvessels may be low. Nodular melanomata tended to have a greater number of
      vessels than did thin superficial spreading lesions. Evaluation of microvessel
      count may be of assistance when coupled with clinical and histologic findings in
      distinguishing between melanoma and Spitz nevus in selected cases.

PMID- 7512804
TI  - Separation of complex oligosaccharide mixtures by capillary electrophoresis in
      the open-tubular format.
AB  - The fluorescent derivatives of complex oligosaccharide mixtures from different
      origins are separated in open capillaries. The number of negatively charged
      sulfonate groups in the tag molecule strongly affects separation efficiency and
      selectivity. Coating of the capillary surface with linear polyacrylamide has been
      essential to ensure fast and stable migration velocities. Efficiencies in excess
      of 1 million plates/m have been achieved, facilitating resolution of branched
      oligosaccharides. The effects of field strength and buffer composition on the
      apparent electrophoretic mobility of dextran and dextrin oligomers are discussed,
      with relation to borate complexation. Preliminary examples of applications to
      monitoring the action of hydrolytic and synthesizing enzymes are also described.

PMID- 7512802
TI  - Cutaneous ciliated cyst of the scalp. A case report with immunohistochemical
      evidence for estrogen and progesterone receptors.
AB  - The cutaneous ciliated cyst (CCC) is an unusual lesion found in young women that
      typically occurs on the lower extremities. This report describes a case of CCC
      arising in the scalp, a previously undescribed anatomic location for this lesion.
      In addition, positive nuclear staining for estrogen and progesterone receptors is
      demonstrated by immunohistochemical methods. Possible pathogenetic mechanisms are
      discussed.

PMID- 7512800
TI  - Neuroendocrine carcinoma of the skin (Merkel cell carcinoma). An immunoelectron
      microscopic case study.
AB  - An unusual tumor with a controversial name as well as histogenesis, the
      neuroendocrine carcinoma of the skin (also known as "Merkel cell carcinoma,"
      "trabecular carcinoma of the skin") has previously been extensively studied by
      immunohistochemical methods at the light-microscopic level. Ultrastructural
      descriptions of this tumor have also been extensive, although immunocytochemical
      study of this neoplasm at the electron-microscopic level has been limited. In
      this report, we have used postembedding protein A-gold immunocytochemistry on
      thin sections from tumor embedded in Lowicryl K4M to investigate the expression
      and ultrastructural localization of a panel of commercially available,
      diagnostically useful antibodies. Antibodies associated with epithelial
      derivation included anti-keratin monoclonal antibody AE1/AE3, polyclonal anti
      keratin, and monoclonal anti-cytokeratin cocktail (MAK-6), as well as a
      monoclonal antibody against epithelial membrane antigen (EMA). Antibodies
      associated with neuroendocrine derivation included monoclonal anti-chromogranin A
      and monoclonal anti-synaptophysin. Although staining with a polyclonal antibody
      directed against neuron-specific enolase (NSE) was equivocal, there was no
      labeling with a monoclonal anti-neurofilament antibody. The finding of positive
      keratin labeling of filaments arranged in paranuclear aggregates correlates well
      with the previously described immunohistochemical staining pattern at the light
      microscopic level. Moreover, the presence of cytoplasmic synaptophysin and
      chromogranin positivity over dense-core granules exemplifies the neuroendocrine
      differentiation present in this fascinating tumor of the skin.

PMID- 7512801
TI  - Three subtypes of poroid neoplasia in a single lesion: eccrine poroma,
      hidroacanthoma simplex, and dermal duct tumor. Histologic, histochemical, and
      ultrastructural findings.
AB  - A single poroid neoplasm composed of three histologically distinct lesions
      (hidroacanthomas simplex, eccrine poroma, and dermal duct tumor) is reported.
      Comparative histologic, histochemical, and electron-microscopic studies revealed
      that each tumor subtype contained varying proportions of poroid cells, clear
      cells, and cuticular cells. The major component of all three neoplasms was poroid
      cells, which, under the electron microscope, were characterized by a few, small,
      poorly developed desmosomes, and were histochemically characterized by a positive
      succinic dehydrogenase reaction. The dermal duct tumor was cultured, and showed
      similar histochemical findings to the in vivo poroid cells. These results suggest
      that poroid cells play the most important role in the histogenesis of these three
      neoplasms.

PMID- 7512805
TI  - Are hypotension and rash after atracurium really caused by histamine release?
AB  - A prospective, randomized, double-blind study was performed in 40 patients (ASA
      class I-III) treated with atracurium to ascertain whether histamine release
      caused hemodynamic or cutaneous changes. The treated group of 20 patients was
      premedicated with the H1 antagonist dimetindene (0.2 mg/kg) and the H2 antagonist
      ranitidine (1.25 mg/kg); the control group of 20 patients received saline. Six
      minutes after the induction of anesthesia with thiopental/fentanyl, patients
      received atracurium 0.5 mg/kg over 5 s. Plasma histamine levels were measured
      fluorometrically 5 min after administration of thiopental/fentanyl and 2 and 5
      min after atracurium. Arterial blood pressure and heart rate were recorded every
      2 min. Histamine levels (0.24 ng/mL) did not change significantly after
      thiopental/fentanyl. In the control group, 2 min after injection of atracurium,
      plasma histamine levels were 0.76 +/- 0.76 ng/mL, and in the antihistamine
      treated group, 0.39 +/- 0.24 ng/mL (P < 0.05 control versus treated), suggesting
      that pretreatment with antihistamines may attenuate atracurium-induced histamine
      release. Systolic and diastolic blood pressure decreased significantly in both
      groups after thiopental (P < 0.05), but did not decrease further after the
      administration of atracurium. There were cutaneous manifestations in 7 of 20
      patients in the control group and in none of the 20 patients treated with H1 and
      H2 antagonists (P < 0.0005). We conclude that atracurium caused modest histamine
      release in our patients but that the decrease in arterial blood pressure may have
      been due, in part, to thiopental. Cutaneous manifestations of histamine release
      did not correlate with hemodynamic events or with plasma histamine levels, but
      were prevented with antihistamine pretreatment.

PMID- 7512806
TI  - A MspI polymorphism at the porcine gamma-glutamyl transpeptidase (GGT) locus.

PMID- 7512807
TI  - Development of an rRNA-targeted oligonucleotide probe specific for the genus
      Acinetobacter and its application for in situ monitoring in activated sludge.
AB  - Enhanced biological phosphate removal in an anaerobic-aerobic activated sludge
      system has generally been ascribed to members of the genus Acinetobacter. A genus
      specific 16S rRNA-targeted oligonucleotide probe was developed to investigate the
      role of Acinetobacter spp. in situ. Nonisotopic dot blot hybridization to 66
      reference strains, including the seven described Acinetobacter spp., demonstrated
      the expected probe specificity. Fluorescent derivatives were used for in situ
      monitoring of Acinetobacter spp. in the anaerobic and aerobic compartments of a
      sewage treatment plant with enhanced biological phosphate removal. Microbial
      community structures were further analyzed with oligonucleotide probes specific
      for the alpha, beta, or gamma subclasses of the class Proteobacteria, for the
      Cytophaga-Flavobacterium cluster, for gram-positive bacteria with a high G + C
      DNA content, and for all bacteria. Total cell counts were determined by 4',6
      diamidino-2-phenylindole staining. In both the anaerobic and the aerobic basins,
      the activated sludge samples were dominated by members of the class
      Proteobacteria belonging to the beta subclass and by gram-positive bacteria with
      a high G + C DNA content. Acinetobacter spp. constituted less than 10% of all
      bacteria. For both basins, the microbial community structures determined with
      molecular techniques were compared with the compositions of the heterotrophic
      saprophytic microbiota determined with agar plating techniques. Isolates on
      nutrient-rich medium were classified by whole-cell hybridization with rRNA
      targeted probes and fatty acid analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512808
TI  - Estimation of diversity and community structure through restriction fragment
      length polymorphism distribution analysis of bacterial 16S rRNA genes from a
      microbial mat at an active, hydrothermal vent system, Loihi Seamount, Hawaii.
AB  - PCR was used to amplify (eu)bacterial small-subunit (16S) rRNA genes from total
      community genomic DNA. The source of total-community genomic DNA used for this
      culture-independent analysis was the microbial mats from a deep-sea, hydrothermal
      vent system, Pele's Vents, located at Loihi Seamount, Hawaii. Oligonucleotides
      complementary to conserved regions in the 16S rRNA-encoding DNA (rDNA) of
      bacteria were used to direct the synthesis of PCR products, which were then
      subcloned by blunt-end ligation into phagemid vector pBluescript II. Restriction
      fragment length polymorphism patterns, created by using tandem tetrameric
      restriction endonucleases, revealed the presence of 12 groups of 16S rRNA genes
      representing discrete operational taxonomic units (OTUs). The rank order
      abundance of these putative OTUs was measured, and the two most abundant OTUs
      accounted for 72.9% of all of the 16S rDNA clones. Among the remaining 27.1% of
      the 16S rDNA clones, none of the 10 OTUs was represented by more than three
      individual clones. The cumulative OTU distribution for 48 bacterial 16S rDNA
      clones demonstrated that the majority of taxa represented in the clone library
      were detected, a result which we assume to be an estimate of the diversity of
      bacteria in the native hydrothermal vent habitat. 16S rDNA fingerprinting of
      individual clones belonging to particular OTUs by using an oligonucleotide probe
      that binds to a universally conserved region of the 16S rDNA fragments was
      conducted to confirm OTU specificity and 16S rDNA identity.

PMID- 7512809
TI  - Synergistic effects of bombesin and cholecystokinin on cholesterol esterase
      biosynthesis and secretion by AR42J cells.
AB  - This study used the rat pancreatoma AR42J cells as model to study hormonal
      regulation of cholesterol esterase biosynthesis. Our previous studies (Y. Huang
      and D. Y. Hui, 1991, J. Biol. Chem. 266, 6720-6725) have demonstrated that the
      AR42J cells responded to cholecystokinin (CCK) and secretin challenge by
      increasing cholesterol esterase biosynthesis. The current investigation showed
      that another gastric peptide hormone, bombesin, was also effective in stimulation
      of cholesterol esterase biosynthesis. Cholesterol esterase biosynthesis in AR42J
      cells increased 2- to 3-fold in the presence of 5 to 10 nM bombesin or 4 nM CCK.
      More significantly, when both bombesin and CCK were added to the incubation
      medium at these concentrations simultaneously, a 15-fold induction of cholesterol
      esterase biosynthesis was observed. Slot-blot analysis of RNA isolated from
      control and hormone-stimulated cells revealed no change in the level of
      cholesterol esterase mRNA, suggesting the post-transcriptional activation of
      cholesterol esterase biosynthesis. The synergism between bombesin and CCK was not
      restricted to cholesterol esterase biosynthesis as the simultaneous addition of
      the two hormones also dramatically increased amylase secretion by AR42J. The
      results of these studies indicated that gastric peptide hormones may act in
      concert to stimulate maximally digestive enzyme biosynthesis. The synergistic
      effects of bombesin and CCK also suggest that distinctive signal transduction
      pathways may be responsible for the bombesin and CCK induction of pancreatic
      protein secretion.

PMID- 7512811
TI  - [Comparative study on the activity of some enzyme systems in cells of gramicidin
      S sensitive and resistant strains of Staphylococcus aureus].
AB  - Polarographic determination of the rate of endogenic respiration of the cells of
      Staphylococcus aureus 209P showed that the respiration activity of the cells of
      the strain resistant to 20 micrograms/ml of gramicidin S was 20 to 30 per cent
      lower than that of the sensitive strain. The rate of oxygen consumption in
      oxidation of NADH by the membrane preparations of the resistant cells was also 25
      to 30 per cent lower. By comparison with the initial sensitive strain the
      activity of endogenic DPI-reductases of the intact cells and NADH-dehydrogenases
      of the membranes of the resistant strain was also lower. The velocity of the
      valine transport to the resistant cells was much lower than that of the amino
      acid transport to the cells of the sensitive strain. Development of gramicidin S
      resistance in the staphylococcal strain was likely accompanied by a decrease in
      the activity of the energy metabolism in the membranes.

PMID- 7512810
TI  - Cytokines, the acute-phase response, and resting energy expenditure in cachectic
      patients with pancreatic cancer.
AB  - OBJECTIVE: To determine whether resting energy expenditure (REE) is increased in
      cachectic patients with pancreatic cancer and to define the relation of tumor
      necrosis factor (TNF) and interleukin-6 (IL-6) production to the acute-phase
      response and to REE. METHODS: Measurement of REE (indirect calorimetry) and
      assessment of body composition (bioelectrical impedance analysis) were done in 21
      patients with unresectable pancreatic cancer and on 16 age-related controls. The
      systemic inflammatory response in peripheral blood of the cancer patients was
      assessed using the acute-phase protein, C-reactive protein, and the cytokines TNF
      and IL-6. Production of these cytokines by peripheral blood mononuclear cells in
      vitro was also measured. RESULTS: Patients with pancreatic cancer had an elevated
      REE when compared with controls (73.4 +/- 5.0 vs. 53.5 +/- 1.6 kcal/kg body cell
      mass; p < 0.003). Resting energy expenditure was significantly greater in cancer
      patients with an acute-phase response (C-reactive protein > 10 mg/L) than in
      those who did not have such a response (85.5 +/- 10.0 [n = 9] vs. 64.3 +/- 3.0 [n
      = 12] kcal/kg body cell mass; p < 0.04). Tumor necrosis factor was not detected
      in the serum of any of the cancer patients. Serum IL-6 was detected but levels
      were not significantly different among cancer patients with or without an acute
      phase response. In contrast, spontaneous production of TNF and IL-6 by isolated
      peripheral blood mononuclear cells was significantly greater in cancer patients
      with an acute-phase response that in those without (TNF: 1231 +/- 244 vs. 210 +/-
      54 pg/ml/10(5) cells; p < 0.001; IL-6: 11.5 +/- 1.7 vs. 3.6 +/- 1.4 ng/mL/10(5)
      cells; p < 0.003). CONCLUSIONS: In pancreatic cancer at least a component of
      weight loss is due to increased REE. Furthermore, the presence of an acute-phase
      response identifies a group of patients who are markedly hypermetabolic. The
      serum concentration of TNF of IL-6 does not correlate with the presence of an
      acute-phase response, whereas rates of cytokine production by peripheral blood
      mononuclear cells are significantly greater in patients with such a response.
      This suggests that local rather than systemic cytokine production may be
      important in regulating the acute-phase response.

PMID- 7512812
TI  - [Partial endoscopic resections with CO2 laser in laryngeal cancer. I. Resection
      techniques].
AB  - The laser surgical technique as used in more than 250 laryngeal carcinomas since
      1979 is described. The CO2 laser is always used as a cutting instrument and not
      to vaporize the tumour, since this would not enable a control of complete tumour
      removal. The vaporisation technique is used only in combination with the cutting
      technique for laser surgical debulking of large laryngeal tumours. Five cutting
      techniques are differentiated: 1) excisional biopsy; 2) excision of the tumour in
      several portions; 3) incision of large tumours for staging purposes; 4)
      palliative excision of primary tumours in inoperable lymph node metastases; 5)
      palliative reduction of large tumours (debulking). T1a vocal cord carcinomas and
      circumscribed carcinomas of the border of the epiglottis are resected by means of
      a so-called excisional biopsy. This means that the tumour is resected in toto
      with a small line of adjoining healthy tissue. For the removal of large
      carcinomas of the vocal cord, or of tumours that cross the anterior commissure,
      or of larger supraglottic tumours, an unusual technique is employed. The tumorous
      tissue is cut with the laser and resected in several fragments. This may seem to
      contradict current oncological principles and is only possible because of laser
      specific tissue reactions. When using a modern micromanipulator (711 Acuspot,
      Sharplan, London; diameter of the laser beam: 0.25 mm at 400 mm working distance)
      at low power levels (1-2 watts) and continuous wave mode, very slight or no
      bleeding is caused on the surface of the dissected tissue allowing
      differentiation between tumour and healthy tissue with the operating
      microscope.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512813
TI  - [Micrometastases in bone marrow of patients with cancers in the head and neck
      area].
AB  - Individual disseminated epithelial tumour cells were detected in bone marrow
      aspirates in 41 of 108 patients (37%) with squamous cell cancer of the head and
      neck region by an immunocytochemical technique based on monoclonal antibodies
      raised against the cytokeratin No. 19. In the clinical stage I (T1N0M0) tumour
      cells were detected only in 26.3% of the patients, whereas in stage IV (T4N0M0,
      T(all)N2-3M0, T(all)N(all)M1) almost twice as many patients (47.7%) presented
      with tumour cells in the bone marrow. Apparently, grade of differentiation of the
      tumour (grading) had no influence on the spread of single tumour cells. An
      influence of the different localisations of the primary tumour on tumour cell
      spread or the rate of tumour recurrence cannot as yet be discovered. Cytokeratin
      No. 19 expressing cells were not detectable in the bone marrow of 18 patients
      with non-malignant disease. Seventy-three patients were included in a follow-up
      study with a mean observation time of 25 months (range: 4-52 months). The
      presence of epithelial cells at the time of primary treatment appears to indicate
      a significantly higher risk of development of local or distant tumour recurrences
      (p = 0.01). Of 46 patients initially exhibiting no tumour cells in the bone
      marrow, only 14 had a clinical recurrence. Whereas 17 of 27 patients who
      presented with tumour cells in the bone marrow developed either a local tumour
      recurrence or distant metastases in different organs. Patients presenting with
      bone marrow tumour cells showed a significantly shorter disease-free survival
      than those without (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512814
TI  - Cloning and expression in Escherichia coli of the gene encoding the Proteus
      vulgaris chondroitin ABC lyase.
AB  - The structural gene encoding chondroitin ABC lyase from Proteus vulgaris was
      cloned and sequenced. This gene consists of a single open reading frame of 3,063
      bp, including a sequence (72 bp) for a possible secretory protein leader peptide,
      preceded by a Shine-Dalgarno ribosomal binding site. Promoter-like and rho
      independent terminator sequences were detected upstream and downstream of the
      open reading frame, respectively. The G+C content of the coding region was 38.6%.
      The transcription startpoint was located 41-bp upstream of the initiation codon
      (ATG). Chondroitin ABC lyase is composed of 997 amino acids, and has a relative
      molecular mass of 112,635. When the 5.2-kb fragment containing the 1.2-kb
      upstream from the gene was inserted into pSTV29, and cloned in Escherichia coli,
      chondroitin ABC lyase was induced in the medium containing chondroitin-6-sulfate
      as the carbon source. On the other hand, when a 4.2-kb fragment containing only
      0.2 kb upstream was inserted into pSTV29(pCHS delta 6), and pCHS delta 6 was
      introduced into E. coli, the enzyme was constitutively produced, even in medium
      containing glucose as the carbon source. By immunoblot analysis, the polypeptide
      synthesized by E. coli cells carrying pCHS delta 6 appeared to be the same as
      that of the purified chondroitin ABC lyase from P. vulgaris.

PMID- 7512816
TI  - p75LNGFR regulates Trk signal transduction and NGF-induced neuronal
      differentiation in MAH cells.
AB  - We have examined NGF-induced signal transduction events and neuronal
      differentiation in MAH cells, a neuronal progenitor cell line, in which the
      expression of the two NGF receptors, p140trk (Trk) and p75LNGFR (p75), has been
      independently manipulated. Coexpression of a large molar excess of p75
      substantially enhances the NGF-induced tyrosine autophosphorylation of Trk,
      compared with cells expressing Trk alone. MAH cells expressing both Trk and p75
      stop dividing and acquire a mature neuronal morphology more rapidly and with
      greater efficiency than MAH cells expressing Trk alone. These biochemical and
      biological influences of p75 are not observed using a mutant form of NGF that
      binds Trk but not p75. These data provide evidence that p75 can modulate signal
      transduction through Trk in a neuronal progenitor cell context and that such
      modulation has functional consequences for the neuronal differentiation pathway
      induced by NGF.

PMID- 7512818
TI  - [Genetic polymorphism of inter-alpha-trypsin-inhibitor (ITI) in a Han population
      in China].
AB  - Phenotypes of inter-alpha-trypsin-inhibitor (ITI) have been determined by
      isoelectric focusing on the polyacrylamide gel followed by immunofixation. The
      phenotype frequencies of ITI in the Han population in Chengdu, China were
      investigated using this method. In addition, family studies have been conducted
      in 21 families. The results showed that the ITI was polymorphic in the Han
      population in Chengdu. The allele frequencies were as follows: ITI*1 = 0.5763,
      ITI*2 = 0.4107, ITI*3 = 0.0130. It was obvious that the ITI is a new and
      promising genetic marker which can be used in the field of forensic
      haematogenetics.

PMID- 7512817
TI  - Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion
      molecule L1.
AB  - The nonreceptor tyrosine protein kinases pp60c-src, p59fyn, and pp62c-yes are
      localized in growth cones of developing neurons, but their function is undefined.
      To determine whether these tyrosine kinases were capable of regulating substrate
      dependent axon growth, cultures of cerebellar neurons from wild-type, src-, fyn-,
      and yes- mice were analyzed for neurite outgrowth on the neural cell adhesion
      molecule L1 or the extracellular matrix protein laminin. The rate of neurite
      extension on L1 was reduced in src-, but not in fyn- or yes- neurons. Neurite
      extension on laminin was unaltered in src-, fyn-, or yes- neurons, indicating
      that pp60c-src, p59fyn, or pp62c-yes is not likely to participate in integrin
      dependent axon growth. These results demonstrate that pp60c-src is a component of
      the intracellular signaling pathway in L1-mediated axonal growth and suggest that
      Src-related nonreceptor tyrosine kinases may have distinct, nonredundant
      functions in the nervous system.

PMID- 7512815
TI  - Crystal structure of tandem type III fibronectin domains from Drosophila
      neuroglian at 2.0 A.
AB  - We report the crystal structure of two adjacent fibronectin type III repeats from
      the Drosophila neural cell adhesion molecule neuroglian. Each domain consists of
      two antiparallel beta sheets and is folded topologically identically to single
      fibronectin type III domains from the extracellular matrix proteins tenascin and
      fibronectin. beta bulges and left-handed polyproline II helices disrupt the
      regular beta sheet structure of both neuroglian domains. The hydrophobic
      interdomain interface includes a metal-binding site, presumably involved in
      stabilizing the relative orientation between domains and predicted by sequence
      comparision to be present in the vertebrate homolog molecule L1. The neuroglian
      domains are related by a near perfect 2-fold screw axis along the longest
      molecular dimension. Using this relationship, a model for arrays of tandem
      fibronectin type III repeats in neuroglian and other molecules is proposed.

PMID- 7512819
TI  - Feasibility and limitations of a cytometric DNA ploidy analysis procedure in
      tissue sections.
AB  - To produce IOD histograms from tissue sections interpretable in terms of DNA
      ploidy, compromises between section thickness, nuclear volume and cellularity
      have to be found. In most cases, some kind of correction for capping effects will
      be inevitable. One of the correction procedures for that purpose was studied,
      i.e. that concerning the extent of errors which are necessarily introduced by
      assuming a distributional model of nuclei in the tissue slide. This procedure is
      mainly based on the assumptions of a spherical shape of the nuclei, of their
      homogeneous chromatin distribution, and of an equal distribution of the
      equatorial plane inside the tissue slide sectioned. Measurements on rat liver
      sections with a series of section thicknesses demonstrated that the correction
      procedure would lead to an exact position of the IOD peaks from the tetraploid
      nuclei on the ploidy axis. The width of the IOD peaks will not be diminished
      considerably as compared to uncorrected IOD histograms. Therefore, there are
      serious limitations to the procedure as compared to the DNA ploidy analysis on
      smears or imprints. If applied very critically in the case of tissue sections,
      the method may provide additional information about the DNA ploidy in those cases
      which lack a uniform tumour cell population or adequate material for smear
      preparations.

PMID- 7512820
TI  - [DNA cytometry using paraffin embedded tumor tissues. Comparison of flow
      cytometry (FCM) and image cytometry (ICM)].
AB  - In order to examine the correlation of cytometric DNA ploidy in paraffin-embedded
      tumour material, a comparison was made of flow (FCM) and image cytometry (ICM);
      in the case of ICM FEULGEN-stained tissue sections (8-10 microns) and in some
      cases nuclear suspensions were used. Tumour tissue from seminomas (FCM: n = 50;
      ICM/section: n = 28), oral squamous carcinomas (FCM: n = 110; ICM/section: n =
      50) and adenocarcinomas of the gallbladder (FCM: n = 50; ICM/section: n = 46;
      ICM/nuclear susp.: n = 40) was studied. The concordance regarding diploid/non
      diploid characteristics was 96.5% in the case of seminomas, 87% in oral
      carcinomas and 100% in gallbladder carcinomas. A statistically significant
      correlation of DNA indices of FCM with ICM histograms was found in all three
      organ tumours examined. 6% of oral and up to 18% gallbladder carcinomas, however,
      could not be evaluated by means of FCM due to poor quality of the histograms
      (coefficient of variation (CV) > 6%). In the determination of DNA indices and
      resolution of multiploid stemlines, FCM analysis proved to be superior. Regional
      intratumoural differences and rare tumour populations were best detected by ICM
      using sections. Without correction factors being used, these sections did not
      show any significant deviation of DNA indices from the other methods used. Our
      study has revealed that in paraffin-embedded tumour material FCM and ICM usually
      provide well-correlating results, when standardised and controlled preparation
      and measuring procedures are applied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512822
TI  - [Problems concerning standardization and quality assurance in DNA cytometry].
AB  - Rat liver imprints were treated with five different fixation techniques. Chicken
      erythrocytes stored over an extended period in the refrigerator were dropped on
      each slide before Feulgen staining. By means of an image analysis system chicken
      erythrocytes, rat leukocytes and hepatocytes were measured and the integrated
      optical density (IOD) was calculated for each nucleus. The coefficient of
      variation (CV) of IOD was about 15% for chicken erythrocytes. Leukocytes showed a
      CV of up to 10%. The CV was lower for hepatocytes than for leukocytes, and lowest
      for air-dried hepatocytes. The standard error of the mean (SEM) did not show
      remarkable differences between the fixation groups. For hepatocytes it was in
      general less than 1% of the respective mean value. The hepatocytes showed a
      linear staining except the wet formalin-fixed cells. This holds also for the wet
      formalin fixed leukocytes which showed only 85% of the IOD of 2c hepatocytes. The
      ratios of erythrocytes to 2c hepatocytes varied between 0.33 and 0.35. The IOD
      ratios of standard cells to 2c hepatocytes from single specimens showed
      remarkable differences from the above mentioned ratios of the pooled slides of a
      fixation group. The use of external standard cells was proved to be problematic,
      especially because of their variation in staining intensity independent of the
      staining intensity of hepatocytes.

PMID- 7512821
TI  - [DNA and MST entropy and current of entropy. New parameters of tumor biological
      characterization].
AB  - The clinical significance of the entropy of the integrated optical density E
      (IOD) and the corresponding entropiefluss EF (IOD) is discussed as well as the
      structural entropy E (MST) and its entropiefluss EF (MST). The E (IOD) is based
      upon the formula given by Stenkvist and Strande. It describes the statistical
      entropy of the DNA distribution of tumor cell nuclei; the E (MST) is based upon
      differences in IOD and distance between neighboring tumor cell nuclei and
      describes the deviation of tumor structure from a "biological constant"
      structure. The entropiefluss measures the current of entropy or irreversibly
      created heat which has to be removed through the surface of the tumor. It is a
      universally valid description of a thermodynamically open system and measures the
      distance of such a system from its equilibrium stage. The clinical significance
      of these parameters is tested on 241 specimens of human lung carcinomas and
      intrapulmonary metastases of extrapulmonary malignancies. The surgical specimens
      were fixed with buffered formalin. Histological sections cut from paraffin
      embedded tissue were FEULGEN stained. The nuclei of the histomorphological images
      were segmented using an automated image analyzing system, and the attributed
      minimum spanning trees (MST) were calculated. The following results were
      obtained: The measured E (IOD) and E (MST) showed significant differences in the
      primary carcinomas compared to those measured in intrapulmonary lymph node
      metastases or intrapulmonary metastases. The survival of patients was remarkably
      improved if the carcinomas displayed a low E (MST), EF (IOD), and EF (MST).

PMID- 7512823
TI  - Interlaboratory comparison of DNA image analysis. Management group report of
      internal quality assurance programme in the CAAC breast cancer project.
AB  - The Clinically Applied Analytical Cytometry (CAAC) project was a concerted action
      project in a working group measuring DNA in breast cancer. An internal quality
      assurance programme was established on a voluntary basis to determine the level
      of concordance of DNA measurements between participating laboratories. Three
      rounds were achieved within the time scale of the project. For each round three
      slides (2 prepared with Feulgen, one unstained for "in house" preparation)
      bearing a population of human liver cells were sent to participating
      laboratories. The institutions were asked to measure 200 diploid, 100 tetraploid
      and 50 octaploid cells by means of the image cytometry system present in the
      laboratory. In the third round tumor cells were added. The features integrated
      optical density (IOD) and AREA were reported. In the three rounds the number of
      participating laboratories was 11, 14 and 11, respectively. The interlaboratory
      variation expressed as the CV of IOD for the three rounds ranged from 2-18%.
      Calculation of the 4c/2c and 8c/2c ratios revealed a high precision for most of
      the instruments. Comparison of measurements in specimens stained in the
      participating and central laboratory showed similar CV values. Measuring 200
      nuclei in image analysis is too low a number to obtain a reliable estimate of the
      S-phase fraction. In conclusion, the interlaboratory intercomparison of DNA
      measurements performed on different instruments is well feasible and could
      facilitate improvement in quality standards.

PMID- 7512824
TI  - [DNA ploidy and prognosis of cardia and stomach carcinomas. A comparative flow
      and image cytometric analysis pf paraffin-embedded tumor sections].
AB  - The prognostic relevance of DNA stem line ploidy was ascertained by comparative
      DNA analysis performed by flow cytometry (FCM) and by Feulgen image cytometry
      (ICM) of histologic slides on paraffin-embedded resection material from 221
      carcinomas of the cardia and stomach. While flow cytometric detection of DNA stem
      line aneuploidy was rather insecure in smaller or diffuse carcinomas, the
      methodological restrictions of ICM were seen in a reduced measuring accuracy
      varying from one case to the other. This resulted in a lower security in
      distinguishing mere peridiploidy from real hyperdiploid DNA aneuploidy. Despite
      the difference of methodology, the results were principally concurring. The
      assessment of DNA stem line ploidy offered no appreciable information about the
      prognosis of Lauren's diffuse carcinomas. For intestinal carcinomas, however,
      there was a significant positive correlation between DNA stem line aneuploidy and
      the evidence of regional nodal metastases, which might explain to a considerable
      extent the significantly unfavorable clinical course of tumor cases with recorded
      DNA aneuploidy. The correlation between DNA stem line ploidy, nodal status, and
      clinical outcome was distinctly less strong in intestinal carcinomas of the
      cardia than in those of the stomach, because nodal metastatic spread of cardia
      carcinomas is strongly influenced by local conditions of lymph drainage and the
      special mechanical strain.

PMID- 7512825
TI  - Three-dimensional solution structure of the extracellular region of the
      complement regulatory protein CD59, a new cell-surface protein domain related to
      snake venom neurotoxins.
AB  - The cell surface antigen CD59 is an inhibitor of complement-mediated lysis and a
      member of the Ly6 superfamily (Ly6SF) of cysteine-rich cell-surface molecules
      whose sequences are related to those of snake venom neurotoxins. The three
      dimensional solution structure of a recombinant form of the extracellular region
      of the molecule (residues 1-70 of the mature protein; sCD59) has been solved by
      2D NMR methods. sCD59 is a relatively flat, disk-shaped molecule consisting of a
      two-standed beta-sheet finger loosely packed against a protein core formed by a
      three-stranded beta-sheet and a short helix. Structure calculations allowed an
      unambiguous assignment of the disulfide-bonded cysteine pairs as 3-26, 6-13, 19
      39, 45-63, and 64-69. The topology of sCD59 is similar to that of the snake venom
      neurotoxins and consistent with an evolutionary relationship existing between the
      Ly6SF and the neurotoxins.

PMID- 7512826
TI  - Interaction of recombinant granulocyte colony stimulating factor with lipid
      membranes: enhanced stability of a water-soluble protein after membrane
      insertion.
AB  - The interaction of recombinant granulocyte colony stimulating factor (rhG-CSF)
      with lipid vesicles was studied. In the presence of dioleoylphosphatidylglycerol
      (DOPG) vesicles, the intrinsic fluorescence of rhG-CSF exhibits dramatic changes.
      In particular, tryptophan fluorescence is greatly enhanced and the emission
      maximum shifted to lower wavelengths. The presence of DOPG vesicles causes the
      protein tryptophans to become inaccessible to iodide, a water-soluble quencher of
      tryptophan fluorescence, yet accessible to quenching via energy transfer to
      pyrenyl decanoic acid, a lipid-soluble fluorescent probe. The data suggest that
      rhG-CSF inserts into lipid vesicles composed of DOPG. The driving force for the
      insertion may be a conformational change induced by the low pH at the lipid-water
      interface of DOPG vesicles. The DOPG-inserted form of rhG-CSF retains biological
      activity and shows remarkable stability, even under high-temperature conditions
      which lead to denaturation of rhG-CSF alone. Membrane insertion of G-CSF may be
      involved in the in vivo activity of this important cytokine.

PMID- 7512828
TI  - [Is the early diagnosis of a pancreatic neoplasm possible? A report and
      comparison of 2 clinical cases].
AB  - Following a critical review of the international literature on the subject of
      cancer of the pancreas, the authors report two case studies of this pathology,
      one of which was diagnosed at a preclinical stage and underwent radical surgical
      exeresis. The authors draw attention to two factors which must be taken into
      consideration in this pathology: firstly, the need to extend screening tests in
      the group of high-risk patients, above all in those who drink three or more cups
      of coffee a day; secondly, to re-evaluate the diagnostic use of two
      hematochemical tests, lipasemia and amylasemia, which are easily performed and
      available in all clinical laboratories.

PMID- 7512827
TI  - Identification of the sulfated monosaccharides of GlyCAM-1, an endothelial
      derived ligand for L-selectin.
AB  - L-Selectin, a receptor bearing a C-type lectin domain, mediates the initial
      attachment of lymphocytes to high endothelial venules of lymph nodes. One of the
      endothelial-derived ligands for L-selectin is GlyCAM-1 (previously known as
      Sgp50), a mucin-like glycoprotein with sulfated, sialylated, and fucosylated O
      linked oligosaccharide chains. Sialylation, sulfation, and fucosylation appear to
      be required for the avid interaction of this ligand with L-selectin, but the
      exact carbohydrate structures involved in recognition remain undefined. In this
      study, we examine the nature of the sulfate-modified carbohydrates of GlyCAM-1.
      GlyCAM-1 was metabolically labeled in lymph node organ culture with 35SO4 and a
      panel of tritiated carbohydrate precursors. Mild hydrolysis conditions were
      established that released sulfated oligosaccharides without cleavage of sulfate
      esters. Low molecular weight and singly charged fragments, obtained by a
      combination of gel filtration and anion-exchange chromatography, were analyzed.
      The structural identification of the fragments relied on the use of a variety of
      radiolabeled sugar precursors, further chemical and enzymatic hydrolysis, and
      high-pH anion-exchange chromatography analysis. Sulfated constituents of GlyCAM-1
      were identified as Gal-6-SO4, GlcNAc-6-SO4, (SO4-6)Gal beta 1-->4GlcNAc, and Gal
      beta 1-->4(SO4-6)GlcNAc. In the accompanying paper [Hemmerich, S., & Rosen, S.D.
      (1994) Biochemistry 33, 4830-4835] evidence is presented that (SO4-6)Gal beta 1-
      >4GlcNAc forms the core of a sulfated sialyl Lewis x structure that may comprise
      a recognition determinant on GlyCAM-1.

PMID- 7512831
TI  - Immunocytochemical localization of distinct isoforms of nitric oxide synthase in
      the juxtaglomerular apparatus of normal rat kidney.
AB  - Nitric oxide (NO) is a messenger molecule that functions as a vasodilator and
      accounts for the biologic activity of endothelium-derived relaxing factor (EDRF).
      The enzyme responsible for NO production, NO synthase (NOS), exists in different
      isoforms. Some are expressed constitutively in various tissues, whereas others
      require induction by endotoxin and cytokines. There is evidence that NO plays an
      important role in the regulation of basal renal vascular resistance and in the
      tubuloglomerular feedback response. Specific antibodies to a constitutive NOS
      isolated from rat brain (B-NOS) and an inducible NOS isolated from rat aortic
      smooth muscle (VSM-NOS) were used to establish the cellular and subcellular
      distribution of NOS in the kidney. Kidneys from normal rats were preserved and
      processed for light and electron microscopic immunohistochemical studies using
      both a preembedding and a postembedding horseradish peroxidase technique. By
      light microscopy, strong immunostaining for B-NOS was observed in the
      juxtaglomerular apparatus, where it was located in cells of the macula densa. In
      contrast, immunostaining for VSM-NOS was specifically located in the terminal
      afferent arteriole and occasionally also in the initial efferent arteriole in the
      juxtaglomerular apparatus. In addition, faint immunostaining was present in the
      entire distal tubule. There was no labeling of arcuate or interlobular arteries.
      The injection of lipopolysaccharide was associated with increased immunostaining
      for VSM-NOS in the afferent arteriole but had no effect on B-NOS staining. By
      electron microscopy, B-NOS immunostaining was present throughout the cytoplasm of
      the macula densa cells, where it appeared to be associated mainly with small
      vesicles. Immunostaining for VSM-NOS in the afferent arteriole exhibited a patchy
      distribution in some cells, whereas other cells were stained throughout the
      cytoplasm. These results indicate that two distinct isoforms of NOS are present
      in the juxtaglomerular apparatus and support the hypothesis that NOS is involved
      in the regulation of tubuloglomerular feedback and glomerular capillary pressure.

PMID- 7512832
TI  - Detection of hepatitis C virus RNA in hemodialysis patients.
AB  - The clinical significance of the high prevalence of antibodies to hepatitis C
      virus (HCV) in dialysis patients remains undefined. In order to assess the
      relationship between seropositivity and potential infectivity, 63 patients
      undergoing maintenance hemodialysis were evaluated between April and May 1990.
      The mean duration of maintenance hemodialysis was 45 mo (range, 13 to 144).
      Eighty-two percent (52 of 63) had received blood transfusions, and 16% (10 of 63)
      had a history of iv drug abuse. Serum samples were analyzed by HCV-cDNA
      polymerase chain reaction; antibodies to HCV structural (core) and nonstructural
      regions NS3 and NS4 were determined by enzyme immunoassay. Specimens repeatedly
      reactive for anti-HCV and HCV-RNA-positive samples were tested by HCV MATRIX dot
      immunoblot assay and HBV-DNA PCR. Twenty-five percent (16 of 63) were anti-HCV
      positive. Of the 16 anti-HCV-positive patients, HCV-RNA was detected in 5 (31%)
      with the NS3 primers and in 12 (75%) with 5'-noncoding primers. Among the anti
      HCV-negative patients, HCV-RNA was detected in 2 (4.3%) of 47 patients. Eleven of
      the 18 patients with HCV infection (anti-HCV and/or HCV-RNA-positive) had
      evidence of additional present or past viral infections (human immunodeficiency
      virus and/or hepatitis B virus). In summary, HCV-RNA is present in at least 75%
      of anti-HCV-positive patients, suggesting that they may be infectious. The
      detection of HCV-RNA in anti-HCV-negative patients may indicate early or chronic
      HCV infection not detected by current antibody assays or the inability of these
      patients to mount or sustain a significant antibody response.

PMID- 7512833
TI  - Sequential promotion of normal and leukemic hemopoiesis by recombinant human
      granulocyte colony-stimulating factor during the course of myelodysplastic
      syndrome.
AB  - A 48-year-old man developed refractory anemia with excess of blasts in
      transformation. Complete response was achieved by low-dose ara-C therapy, but he
      relapsed 15 months later, with pancytopenia and 13.0% myeloblasts in
      normocellular marrow. He was treated unsuccessfully with prednisolone,
      metenolone, and 1-alpha-hydroxyvitamin D3 for 8 weeks. He then developed life
      threatening pneumonia and was treated with recombinant human granulocyte colony
      stimulating factor (rhG-CSF Filgrastim; 125 micrograms/day s.c.). The pneumonia
      resolved and, interestingly, he achieved a partial response, with normal blood
      cell counts and only a few dysmyelopoietic cells in the marrow. However,
      thrombocytopenia progressed when rhG-CSF administration was tapered. When the
      dose was increased again, leukemic blasts were found to proliferate. When rhG-CSF
      was discontinued, blasts rapidly decreased in the peripheral blood. Chromosomal
      analysis revealed a complex abnormality during the first relapse, a normal 46,XY
      karyotype during the partial response, and recurrence of the same complex
      abnormality during leukemic transformation. The stimulation index of marrow
      mononuclear cells cultured with rhG-CSF increased with disease progression. These
      findings suggest that rhG-CSF initially stimulated the selective proliferation of
      normal hemopoietic cells, but the evolution or selection of a leukemic clone
      responsive to rhG-CSF appears to have occurred subsequently.

PMID- 7512829
TI  - Resistance of human immunodeficiency virus type 1 to antiretroviral agents: a
      review.

PMID- 7512830
TI  - The barrel-stave model as applied to alamethicin and its analogs reevaluated.
AB  - Alamethicin and its analogs from cation selective, multi-conductance channels in
      lipid bilayers. The conductance levels have been thought to be due to a barrel
      stave structure where conducting pores (barrels) are formed by the self-assembly
      of a variable number of alpha-helical rods (staves). The conductance transitions
      were then interpreted as the addition or deletion of peptide monomers from the
      pore-forming complex (Sansom, M.S. 1991. Prog. Biophys. Mol. Biol. 55:139-235).
      Initially, pore conductances were calculated from that expected of right circular
      cylinders of "bulk" electrolyte. More recent theories also included the access
      resistance of the electrolyte outside the pore. However, they all consistently
      overestimated the observed conductances. The reason for the discrepancy is
      presented here. Previous theories ignored the effects of ion concentration
      gradients near the pore. Hence, they only held in the limit of small bilayer
      potentials (< 25 mV) and so would overestimate measurements that typically used
      much larger potentials (> 100 mV). This theoretical flaw is corrected by using
      Lauger's theory of diffusion-limited ion flow (Lauger, P. 1976. Biochim. Biophys.
      Acta. 455:493-509). Thus, including the effects of ion concentration gradients
      results in a considerable improvement in predicting pore conductances. It is
      found that: 1) the effects of ion concentration gradients must be included in the
      barrel-stave model for it to apply to the available data; 2) previously published
      explanations for the discrepancy between the model and the data, namely the
      "distorted bundle" and the "head-to-tail aggregate" hypotheses are not necessary
      (reviewed by Sansom, 1991).

PMID- 7512834
TI  - Association between the histological diagnosis of tuberculosis and
      microbiological findings.
AB  - The aim of this study was to determine the association between the histological
      diagnosis of tuberculosis and the microbiological findings and to indicate how
      these results affect treatment. Histopathology and microbiology records were
      examined retrospectively. 89 cases were identified between 1984 and 1988. 67%
      were diagnosed as tuberculosis (TB) by both methods, 97% were diagnosed as TB or
      'compatible with TB' by histology. For 7% of these the final diagnosis was found
      to be other than TB. 48% of patients diagnosed as TB on the basis of histology
      alone were treated for TB. 70% were diagnosed as TB by microbiology and treated.
      When matched and appropriate specimens were sent to both departments there was a
      high level of agreement between histopathologists and microbiologists. There was
      a problem with inappropriate specimens sent to microbiology.

PMID- 7512835
TI  - Use of colony-stimulating factors in the treatment of acute myeloid leukemia.

PMID- 7512836
TI  - Interleukin-11: a multifunctional growth factor derived from the hematopoietic
      microenvironment.
AB  - IL-11 is a unique growth factor derived from cells making up the HM. Although
      cloned based on IL-6-like bioactivity, IL-11 and IL-6 have distinct biologic
      profiles (Table 1). IL-11, like many recently cloned growth factors, has
      pleiotropic effects on hematopoietic cells presumably depending on the cytokine
      and cellular environment into which it is introduced. However, some general
      findings are consistent (Table 2). In addition, IL-11 has significant effects,
      either primary or secondary, on nonhematopoietic cells, including neurons, small
      intestine crypt progenitor/stem cells, and preadipocytes. The institution of
      human trials with IL-11 will provide important information on the pharmacologic
      effects of IL-11 on human hematopoietic cells in the context of frequently used
      chemotherapy protocols. The physiologic role(s) of IL-11 are unknown but will
      become clear (at least in the mouse) with gene targeting experiments underway in
      several laboratories.

PMID- 7512838
TI  - A double-blind controlled study of granulocyte colony-stimulating factor started
      two days before induction chemotherapy in refractory acute myeloid leukemia.
      Kohseisho Leukemia Study Group.
AB  - We conducted a prospective, double-blind controlled study to determine the
      efficacy of a recombinant granulocyte colony-stimulating factor (G-CSF, 200
      microgram/m2) starting daily from 2 days before an induction therapy until
      neutrophils recovered to above 1,500/microL or until 35 days after the therapy in
      58 patients with relapsed or refractory acute myeloid leukemia (AML). Twenty
      eight patients in the G-CSF group showed significantly faster recovery of
      neutrophils (P < .001) than 30 patients in the placebo group. The incidence of
      febrile episodes and of documented infections was almost the same in both groups.
      However, among 39 patients who did not show any infectious episodes during the 2
      week period after the start of chemotherapy, the incidence of documented
      infections after the third week tended to be lower in the G-CSF group, but not
      statistically significantly. There was no evidence that G-CSF stimulated the
      growth of AML cells in the bone marrow during the 2-day period before the
      chemotherapy, nor that G-CSF accelerated the regrowth of AML cells during the 5
      week period after the therapy. Fifty percent of patients in the G-CSF group and
      37% in the placebo group had complete remission (CR). Although the rate was
      higher in the G-CSF group, the difference was not statistically significant (P =
      .306). There was no difference between the two groups in event-free survival of
      all patients and in disease-free survival of patients who had achieved CR.

PMID- 7512837
TI  - A human homologue of the Drosophila developmental gene, Notch, is expressed in
      CD34+ hematopoietic precursors.
AB  - Members of the Notch gene family have been shown to mediate cell-fate decisions
      by multipotent precursors in a number of different systems. To determine whether
      members of this family might play a similar role in hematopoiesis, we asked if
      homologues of the Notch gene are expressed in human hematopoietic precursors.
      Using degenerate oligonucleotides corresponding to conserved amino acid sequences
      in known Notch homologues as primers for the polymerase chain reaction (PCR), we
      demonstrated that at least one Notch homologue is expressed in human bone marrow
      CD34+ cells, a population enriched for hematopoietic precursors. Cloning and
      sequencing of the PCR products identified this Notch homologue as TAN-1, a member
      of the Notch family previously cloned from a T-cell leukemia with a translocation
      involving this gene. Subsequent evaluation of bone marrow hematopoietic cells for
      TAN-1 expression using a reverse transcription-PCR assay confirmed the expression
      of TAN-1 in CD34+ hematopoietic precursors, including the immature subset that
      lacks expression of lineage-associated antigens (CD34+lin-). These findings,
      together with the known role of Notch homologues in other systems, suggest that
      members of the Notch family, including TAN-1, may be involved in mediating cell
      fate decisions during hematopoiesis.

PMID- 7512839
TI  - Long-term interleukin-6 administration stimulates sustained thrombopoiesis and
      acute-phase protein synthesis in a small primate--the marmoset.
AB  - Interleukin-6 (IL-6) has been ascribed significant roles in both hematopoiesis
      and the immune response, although its contribution to host defence as a whole is
      poorly understood. Because short-term IL-6 treatment was previously shown to
      stimulate megakaryocytopoiesis, we investigated the effect of long-term
      administration of IL-6 on megakaryocytopoiesis and other systemic parameters in
      nonhuman primates. We chose a small primate, the marmoset (Callithrix jacchus),
      which enabled long-term administration at high doses. Recombinant human IL-6
      (rhIL-6) administered at doses of up to 1,000 micrograms/kg/d over 4 and 9 weeks
      caused a sustained twofold to threefold increase of thrombocyte counts, peaking
      at 4 weeks. Thrombocyte counts declined thereafter, despite continuing IL-6
      administration. The number of bone marrow megakaryocytes at 4 and 9 weeks was not
      increased compared with controls, but the ploidy grade was augmented, suggesting
      that IL-6 effects are restricted to mature megakaryocytes in vivo. An acute-phase
      protein response was observed within 24 hours after the first IL-6 administration
      and reached a maximum after 1 week of IL-6 administration at 25 micrograms/kg.
      Serum C-reactive protein, haptoglobin, and ceruloplasmin were increased, whereas
      albumin and transferrin levels declined. The acute-phase protein response was not
      associated with any morphologic evidence of hepatocellular damage. The increased
      levels of Ig and soluble IL-2 receptor in the serum levels reflected systemic
      immunostimulation. There was no evidence of renal mesangioproliferative
      pathology. Antibodies against rhIL-6 developed within 2 weeks, continuously
      increasing during the course of the study. High titers of neutralizing antibodies
      appeared concomitantly with the decrease in platelet counts and decline in acute
      phase proteins. Therefore, despite the pleiotropic effects of IL-6 observed in
      vitro, long-term administration of IL-6 caused a selective and sustained
      stimulation of thrombopoiesis in marmosets that was only ablated by the
      appearance of neutralizing antibodies, and high doses were well tolerated in
      marmosets. A long-term targeting of IL-6 to cells of the megakaryocytic lineage,
      without evoking general toxicity, confirms the potential therapeutic usefulness
      of rhIL-6 for the chronic treatment of thrombocytopenic patients.

PMID- 7512841
TI  - c-kit expression in human megakaryoblastic leukemia cell lines.
AB  - A panel of 164 continuous human leukemia-lymphoma cell lines was analyzed for
      expression of c-kit using Northern blotting and reverse transcriptase-polymerase
      chain reaction (RT-PCR). The c-kit transcripts were detectable in cell lines
      assigned to the myeloid (in 7 of 29 by Northern blotting and in 4 of 8 by RT
      PCR), monocytic (in 1 of 24 by Northern blotting and in 3 of 6 by RT-PCR),
      erythroid (in 6 of 8 by Northern blotting and in 5 of 5 by RT-PCR), and
      megakaryoblastic (in 10 of 10 by Northern blotting) lineages, c-kit expression
      was not seen by Northern blotting or RT-PCR analysis in any of the 93 lymphoid
      leukemia, myeloma, or lymphoma cell lines. Treatment of four megakaryoblastic
      cell lines with protein kinase C activators (phorbol ester 12-O
      tetradecanoylphorbol 13-acetate and Bryostatin 1) led to terminal differentiation
      as assessed by morphologic alterations, changes in the surface marker profile,
      and growth arrest. These effects were associated with enhanced c-kit mRNA
      expression. Exposure to all-trans retinoic acid down-regulated c-kit mRNA levels,
      while simultaneously causing morphologic alterations in all four cell lines.
      Stimulation with growth factors (interleukin-3, granulocyte macrophage-colony
      stimulating factor, and insulin-like growth factors I and II), used to assess any
      role of c-kit in proliferative processes, did not lead to significant
      upregulation or downregulation of c-kit expression. The finding of constitutive
      and high expression of c-kit mRNA in all megakaryoblastic leukemia cell lines and
      its modulation by various reagents might further contribute to the understanding
      of megakaryopoietic proliferation, differentiation, and leukemogenesis.

PMID- 7512840
TI  - Phenotype analysis of hematopoietic CD34+ cell populations derived from human
      umbilical cord blood using flow cytometry and cDNA-polymerase chain reaction.
AB  - A strategy to phenotype rare populations of hematopoietic cells expressing the
      cell-surface marker CD34 was studied. The antigenic phenotype of umbilical core
      blood (CB) CD34+ cells was investigated using flow cytometry and compared with
      the mRNA-phenotype determined by cDNA-polymerase chain reaction (cDNA-PCR)
      analysis. The cDNA-PCR method allowed an mRNA evaluation of small numbers of
      cells. Monoclonal antibodies and oligonucleotide primers that recognize myeloid,
      lymphoid, erythroid and platelet/megakaryocytic cell membrane antigens or
      corresponding mRNA transcripts were used. Evaluation by flow cytometry showed
      that the vast majority of CD34+ CB cells coexpressed CD38, CD18, HLA-DR, and
      CD33. Rare subpopulations of CD34+CD38-, CD34+CD18-, CD34+HLA-DR-, and CD34+CD33-
      were also identified. A large proportion of CD34+ CB cells expressed CD13, CD45R,
      and to a lesser extent CD71. The CD36, CD51, and CD61 antigens were identified on
      a small number of CD34+ cells. The three-color flow cytometry analysis showed
      that CD34+ cells stained with antibodies to CD61 and CD36 or CD51 can be divided
      into subsets that may represent progenitor cells committed to the erythroid
      and/or megakaryocytic lineage. A variety of other lineage-specific cell-surface
      antigens including pre-T-cell marker CD7 and markers of early B cells, ie, CD10
      and CD19, were not coexpressed with CD34+. Using the cDNA-PCR it was seen that
      the mRNA phenotype of a small number of sorted CD34+ cells (purity > 98%) was
      negative for the markers CD2, CD14, CD16, CD20, CD21, CD22, CD41b, and
      glycophorin A that are expressed on differentiated cells but positive for CD34,
      CD7, CD19, CD36, and CD61. The results suggest that circulating CD34+CD7+ and
      CD34+CD19+ CB cells cannot be distinguished by flow cytometry but can be detected
      by cDNA-PCR. This indicates that CB either contains very low numbers of these
      progenitors or that the antigen density of CD7 and CD19 on CD34+ cells is below
      the detection limit of the flow cytometer. In contrast to flow cytometry, cDNA
      PCR allows the phenotypic analysis of cells even if their number is small. Thus,
      the cDNA-PCR method can be useful in linking phenotype analyses, ie, markers of
      differentiation, to studies on gene expression within rare populations of
      hematopoietic stem cells.

PMID- 7512842
TI  - Human umbilical vein endothelial cells display high-affinity c-kit receptors and
      produce a soluble form of the c-kit receptor.
AB  - Stem cell factor (SCF) is a hematopoietic growth factor produced by fibroblasts
      and endothelial cells that stimulates the growth of primitive hematopoietic
      cells. SCF triggers cell growth by binding to the c-kit receptor. Because
      endothelial cells can respond to certain hematopoietic growth factors, we tested
      human umbilical vein endothelial cells for display of the c-kit receptor and
      examined the effect of SCF on endothelial cell proliferation, adhesion molecule
      expression, and production of tissue factor. Quantitative binding experiments
      with 125I-SCF showed both high-affinity (Kd = 42 pmol/L) and low-affinity (Kd =
      1.7 nmol/L) c-kit receptors. There were approximately 1,100 high-affinity c-kit
      receptors, and 5,400 low-affinity c-kit receptors per endothelial cell. Enzyme
      immunoassays showed that endothelial cells released soluble c-kit receptor and
      SCF. The transmembrane form of SCF was detected by indirect immunofluorescence
      analysis using monoclonal or polyclonal anti-SCF receptor antibodies. The
      addition of SCF (100 ng/mL) did not alter endothelial cell proliferation over a 7
      day period. Similarly, there was no change in the release of tissue factor or
      expression of inducible endothelial adhesion molecules (intercellular adhesion
      molecule-1, endothelial-leukocyte adhesion molecule-1, and vascular cell adhesion
      molecule-1) measured by enzyme-linked immunosorbant assay at 4 and 24 hours after
      SCF addition. The neutralizing anti-c-kit receptor monoclonal antibody SR-1
      blocked binding of 125I-SCF to the c-kit receptor by 98% but did not alter
      endothelial cell proliferation or adhesion-molecule expression. c-kit receptors
      were also detected on adult endothelial cells lining small blood vessels in
      normal human lymph nodes. These data indicate that normal human endothelial cells
      produce SCF and show high-affinity c-kit receptors that have the capacity to
      dimerize. The lack of response to exogenous SCF may be because of intracellular
      activation of the c-kit receptor via autocrine production of SCF. Alternatively,
      SCF and c-kit may play a role other than stimulation of proliferation, adhesion
      molecule display, or tissue factor production by endothelial cells. The
      production of soluble c-kit receptors by normal human endothelial cells may serve
      to regulate the bioactivity of SCF within the bone marrow microenvironment.

PMID- 7512843
TI  - The human myeloid cell nuclear differentiation antigen gene is one of at least
      two related interferon-inducible genes located on chromosome 1q that are
      expressed specifically in hematopoietic cells.
AB  - We have previously shown that the human myeloid cell nuclear differentiation
      antigen (MNDA) is expressed at both the antigen and mRNA levels specifically in
      human monocytes and granulocytes and earlier stage cells in the myeloid lineage.
      A 200 amino acid region of the MNDA is strikingly similar to a region in the
      proteins encoded by a family of interferon-inducible mouse genes, designated Ifi
      201, Ifi-202, Ifi-203, etc, that are not regulated in a cell- or tissue-specific
      fashion. However, a new member of the Ifi-200 gene family, D3, is induced in
      mouse mononuclear phagocytes but not in fibroblasts by interferon. The same 200
      amino acid region, duplicated in the mouse Ifi-200 gene family, is also repeated
      in the recently characterized human IFI 16 gene that is constitutively expressed
      specifically in lymphoid cells and is induced in myeloid cells by interferon
      gamma. The 1.8-kb MNDA mRNA, which contains an interferon-stimulated response
      element in the 5' untranslated region, was significantly upregulated in human
      monocytes exposed to interferon alpha. Characterization of the MNDA gene showed
      that it is a single-copy gene and localized to human chromosome 1q 21-22 within
      the large linkage group conserved between mouse and human that contains the Ifi
      200 gene family. The IFI 16 gene is also located on human chromosome 1q. Our
      observations are consistent with the proposal that the MNDA is a member of a
      cluster of related human interferon-regulated genes, similar to the mouse Ifi-200
      gene family. In addition, one mouse gene in the Ifi-200 gene family and the human
      MNDA and IFI 16 genes show expression and/or regulation restricted to cells of
      the hematopoietic system, suggesting that these genes participate in blood cell
      specific responses to interferons.

PMID- 7512845
TI  - Differential effect of 4-hydroperoxycyclophosphamide and antimyeloid monoclonal
      antibodies on T and natural killer cells during bone marrow purging.
AB  - Autologous bone marrow (BM) transplantation after high dose therapy is widely
      used to treat acute leukemia, lymphoma, and selected solid tumors. In studies of
      BM purging with chemical agents, monoclonal antibodies (MoAbs), or other agents,
      the emphasis has been on the efficacy of tumor cell removal and sparing of
      hematopoietic progenitor cells. Two commonly used methods of BM purging for
      patients with acute myeloid leukemia have been the drug 4
      hydroperoxycyclophosphamide (4-HC) and (MoAbs) directed to myeloid antigens such
      as CD14, CD15, and CD33. Although both methods of BM purging have potent activity
      against leukemia cells, 4-HC is also quite toxic to normal hematopoietic
      progenitor cells in the same concentrations that are used to deplete leukemia
      cells. To further characterize the cellular composition of BM after purging, we
      examined the effects of MoAbs plus complement and 4-HC on cells of the lymphoid
      lineage in the BM. 4-HC exerted a concentration-dependent cytotoxicity on
      clonogenic T lymphocytes, natural killer (NK) cells, and lymphokine (interleukin
      2)-activated killer (LAK) cells, whereas the anti-CD14 and anti-CD15 MoAbs had
      little effect. At a concentration of 4-HC commonly used for BM purging (60
      micrograms/mL), there were 4 to 5 logs of T-cell depletion and almost complete
      elimination of NK- and LAK-cell activity. In contrast, 4-HC at low concentrations
      (eg, 3 micrograms/mL) spared the majority of lymphoid cells suggesting that low
      concentration 4-HC combined with MoAb purging may be a desirable alternative to
      higher concentration 4-HC. These data indicate that purging with antimyeloid
      MoAbs, but not with 4-HC, spares the function of mature graft lymphocytes.
      Infusion of viable lymphocytes may be important for the transfer of immune memory
      against microbial and neoplastic antigens and may hasten immune reconstitution.
      In addition, mature graft lymphocytes may also be selectively activated and
      expanded in conjunction with interleukin-2 administration after BM
      transplantation.

PMID- 7512848
TI  - A century of poliomyelitis.

PMID- 7512844
TI  - Bone marrow stromal cell blockade of human leukemic cell differentiation.
AB  - Bone marrow (BM) stromal cell inhibition of leukemic cell differentiation was
      studied in cellular coculture experiments. In coculture, a significant percentage
      of cells from the human myeloid leukemic cell lines HL-60, PLB-985, and K562
      adhere to fibroblastic KM-102 BM stromal cells. A sensitive two-color
      immunofluorescence assay was developed to monitor stromal cellular effects upon
      leukemic cell differentiation. After chemical induction with 1 alpha,25
      dihydroxyvitamin D3, strongly adherent HL-60 and PLB-985 cells were inhibited
      from differentiating into more mature monocytic cells, as measured by the
      monocytic surface marker CD14. In contrast, loosely adherent and nonadherent HL
      60 and PLB-985 leukemic cells in the same cocultures, as well as both adherent
      and nonadherent K562 cells induced with phorbol ester, were not blocked in their
      capacity to differentiate. Scanning electron microscopy and intercellular dye
      transfer experiments correlated intimate stromal cell/leukemic cell interaction
      and intercellular communication with the blockade of leukemic cell
      differentiation. These studies indicate that there is significant variability
      among leukemic lines with respect to the nature of their adhesion to stromal
      cells. Moreover, the data implicate gap-junction formation as a potentially
      significant event in stromal cell-mediated leukemic cell regulation.

PMID- 7512846
TI  - Rescue from anti-MHC class II antibody-mediated marrow graft failure by c-kit
      ligand.
AB  - Dogs given 920 cGy of total body irradiation (TBI) followed by autologous marrow
      infusion uniformly achieve sustained hematopoietic reconstitution. We have
      previously shown that administration of the anti-MHC class II monoclonal antibody
      (MoAb) H81.98.21 (IgG2a) at 0.6 mg/kg/d immediately after transplantation results
      in delayed graft failure. A second noncrossblocking anti-MHC class II MoAb, B1F6,
      of the same isotype, at the same dose, did not interfere with sustained
      engraftment, suggesting that the observed effect was epitope dependent. Although
      higher concentrations of B1F6 were required, in the present study both MoAbs
      interfered with the propagation of long-term marrow cultures. When MoAb B1F6 was
      given in vivo at 1.2 mg/kg/d, ie, twice the dose used previously, dogs so treated
      also developed delayed marrow graft failure. Marrow failure with either MoAb
      involved myeloid, erythroid, and megakaryocytic lineages. Administration of
      recombinant canine c-kit ligand/stem cell factor (SCF) for 7 or 21 days
      posttransplant resulted in reversal of graft failure. Although the short course
      did induce a broad transient early peak of granulocytes, the longer course of SCF
      was accompanied by earlier sustained recovery than the short course. In
      conclusion, therefore, marrow graft failure induced by anti-MHC class II MoAb
      does not appear to be epitope dependent, involves all hematopoietic lineages, and
      is overcome by the administration of c-kit ligand.

PMID- 7512847
TI  - Construction of cDNA libraries from limiting amounts of material.
AB  - The use of cDNA libraries has become increasingly widespread as new techniques
      for library construction and analysis have become available. In recent years,
      interest in cell-type or stage-specific gene expression has necessitated the
      construction of cDNA libraries from very small numbers of cells. Recent advances
      in techniques of RNA isolation, cDNA synthesis, library construction, and the use
      of the polymerase chain reaction have made this a realistic goal.

PMID- 7512849
TI  - Role of alpha 3 beta 1 and alpha 2 beta 1 integrins in melanoma cell migration.
AB  - Recent findings indicate that variable expression of beta 1 integrins may play a
      role in differential melanoma cell motility. Primary melanoma (PM) and metastatic
      melanoma (MM) cultures, derived from the same patient, were tested for their beta
      1, alpha 2, alpha 3 and alpha 6 integrin subunit expression and cell migration on
      type IV collagen (CN IV) or laminin (LN). The MM cell line expressed markedly
      increased levels of the beta 1, alpha 2 and alpha 3, but not alpha 6 subunit
      compared to the PM cell line. The MM cell migration rate was significantly higher
      than that of the PM cell line on LN- or CN IV-coated substrates. Furthermore, the
      cell migration rate of both lines was significantly higher (p < 0.001) on these
      substrates than on the control substrates. The MM and PM cell migration was
      significantly inhibited by function-blocking anti-beta 1 and anti-alpha 3 MAbs,
      but not by the anti-alpha 6 MAb tested. In contrast, the anti-alpha 2 MAb
      significantly inhibited MM but not PM cell migration. These data show that the
      alpha 3 subunit plays a significant role in melanoma cell motility on CN IV and
      LN and that the alpha 2 subunit has a significant contribution to the motility of
      the MM cell line.

PMID- 7512850
TI  - [The molecular aspects of the action of the radioprotector indralin].
AB  - The effect of indralin on the metabolic parameters in peripheral blood and organs
      of irradiated dogs and mice have been studied by EPR, NMR and radioisotope
      methods. It has been shown that indralin stimulated biosynthesis of DNA
      precursors as well as of DNA and proteins in the organs and stabilized the rate
      of ATP and glycogen synthesis. As a result indralin reduced considerably the
      changes produced by gamma-irradiation on the macromolecular biosynthesis during
      the early post-irradiation period. Indralin has induced marked favorable changes
      in the rate of macromolecular synthesis, normalized the ATP and glycogen content,
      induced ribonucleotide reductase activity and increased the Fe(3+)-transferrin
      content during development of compensatory-repair response in the irradiated
      animals. Indralin prevented hyperdevelopment of the repair response and its
      breakdown due to radiation-induced exhaustion of viability of many important
      cellular and body systems after irradiation with lethal doses.

PMID- 7512851
TI  - NCAM (CD56)-positive malignant lymphoma.
AB  - CD56 has been found to identify an isoform of the neural cell adhesion (NCAM).
      NCAM is a member of the immunoglobulin superfamily of cell adhesion molecules; it
      is related to a variety of leukocyte antigens and to several cell adhesion
      molecules believed relevant to malignant behavior in a variety of neoplasms. It
      contains polysialic acid, which appears to regulate binding avidity of NCAM and
      other cell adhesion processes. We have identified a group of NCAM-positive
      lymphomas. Compared to a group of NCAM-negative lymphomas, this group exhibited
      frequent involvement of unusual sites and a generally aggressive course. Another
      series of CD56-positive hematolymphoid malignancies has recently been described,
      from Hong Kong; this group also exhibited involvement of unusual sites and
      displayed a very aggressive course. Together these series suggest that NCAM on
      lymphoma is of biological and clinical significance in terms of tumor behavior
      and spread.

PMID- 7512852
TI  - Acute leukemia complicating bone marrow hypoplasia in an adult with Shwachman's
      syndrome.
AB  - Shwachman's syndrome is a rare congenital disorder associated with neutropenia
      and exocrine pancreatic insufficiency. We describe the development of acute
      myeloid leukemia in a 38-year-old patient with Shwachman's syndrome following
      three years of pancytopenia. After chemotherapy the leukemic clone was
      eradicated, however, the patient's bone-marrow hypoplasia persisted beyond 180
      days with neutropenia that responded to administration of granulocyte colony
      stimulating factor. Despite the patient's low erythropoietin levels,
      administration of erythropoietin did not improve his hemoglobin. We review
      previously reported cases of leukemia complicating Shwachman's syndrome with
      emphasis on the persistent risk of complications in patients with congenital bone
      marrow failure syndromes.

PMID- 7512853
TI  - Paroxysmal nocturnal hemoglobinuria with myelofibrosis: progression to acute
      myeloblastic leukemia.
AB  - A 58-year-old male was diagnosed as having paroxysmal nocturnal hemoglobinuria
      (PNH) with myelofibrosis in 1984. The administration of hydroxyurea and low dose
      splenic irradiation were initiated for abdominal distention due to splenomegaly
      in 1987. In May 1990 the patient developed smouldering acute myeloblastic
      leukemia (AML); and the blasts proliferated in response to G-CSF administered for
      refractory pneumonia. The patient died of pneumonia and pleural involvement of
      leukemia in September 1990. FACS analysis of the blasts using anti-decay
      accelerating factor (DAF) (CD55) and CD59 (membrane attack complex inhibition
      factor: MACIF) monoclonal antibodies demonstrated that 25.5% and/or 87.3% of the
      blasts were negative for DAF or CD59 respectively. There is the earlier evidence
      that about 90% leukemic myeloblasts from non-PNH AML patients are positive for
      DAF, and nearly 100% of non-PNH neutrophils have been shown to be positive for
      both DAF and CD59. Our data suggest that the leukemic blasts from this patient
      may have derived from the PNH clone.

PMID- 7512855
TI  - Malignant B cell CD5 membrane phenotype and B cell colony growth in vivo and in
      vitro in patients with B-chronic lymphocytic leukemia: analysis with clinical
      parameters.
AB  - Chronic lymphocytic leukemia (CLL), despite an overall good prognosis, has a
      subgroup of patients with more rapid, aggressive disease. In an attempt to
      generate additional information about the B cell clones in B-CLL which could be
      used as predictive parameters, we analysed CD5 membrane phenotype and B cell
      colony growth in 29 B-CLL patients. CD5, a 67-kd glycoprotein, has been reported
      to be a consistent feature of the malignant B cell membrane phenotype in CLL. We
      used an in vitro B cell colony assay to study the in vitro growth,
      differentiation, and cell surface properties of CLL B cells. Finally, a variety
      of standard clinical parameters were collated for each patient. Monoclonal
      antibodies to both CD5 and CD19 (pan B cell marker) were used to perform 2-color
      flow cytometry on freshly purified CLL B cells and on CLL B cells harvested after
      7 days of in vitro culture. We demonstrate here that CLL B cells are
      heterogeneous with respect to their expression of CD5, and that this expression
      is not fixed but may vary both in vivo and in vitro. In vitro growth potential,
      as measured by the B cell colony assay, was also heterogeneous with three
      subgroups defined as low growth (< 10 colonies), intermediate (10-100 colonies)
      and high growth (> 100 colonies). Furthermore a T cell conditioned medium was not
      found to be a requirement for in vitro colony growth in the majority of CLL B
      cells. In addition, we evaluated the potential correlation of B cell CD5
      phenotype or B cell colony growth on standard clinical parameters.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7512854
TI  - Early intensive therapy with autotransplantation for high-risk Hodgkin's disease.
AB  - The purpose of this trial was to evaluate the efficacy and the tolerance of high
      dose therapy with autologous stem cell transplantation as part of front-line
      therapy in Hodgkin's disease for patients with both adverse prognostic factors:
      high tumor burden at presentation and slow response to initial chemotherapy. In a
      prospective one-center study, 20 consecutive patients with slow response (tumor
      reduction < 75%) (16 pts) or refractory (4 pts) to 3-4 courses of conventional HD
      chemotherapy received high-dose therapy followed with autologous bone marrow (14
      pts) or peripheral blood stem cell (6 pts) transplantation. They were 13 males, 7
      females, median age 26 years (8-45). At the time of initial diagnosis, all but
      one of the patients had B symptoms, all had high-risk HD defined as Ann Arbor
      stage IV (7 pts) or large mediastinal involvement (LMI = tumor/thorax > 0.45 at
      T5-T6) (6 pts) or both stage IV+LMI (7 pts). Median time between diagnosis and
      autotransplantation was 5 months. Intensive therapy consisted of either CBV
      (cyclophosphamide 1.5 g/m2 x 4, BCNU 300 mg/m2, etoposide 200 mg/m2 x 3) (12 pts)
      or cyclophosphamide 120 mg/kg + 12 Gy total body irradiation for 8 patients with
      diffuse bone or lung involvement. For pts treated with CBV, 40 Gy involved field
      radio-therapy was performed after hematological recovery. Median duration of
      neutropenia was 16 days (9-21). Neither veno-occlusive disease, nor interstitial
      pneumonitis nor toxic death were observed. Seventeen pts are alive with no
      progression of the disease (16/16 in partial response after initial chemotherapy,
      1/4 with refractory disease).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512857
TI  - Tetranucleotide length polymorphism 5' of the alpha 2-macroglobulin receptor
      (A2MR)/LDL receptor-related protein (LRP) gene.

PMID- 7512856
TI  - [Epidemiology of rheumatoid arthritis].

PMID- 7512858
TI  - A dinucleotide repeat in the third intron of CD36.

PMID- 7512859
TI  - The gene for Darier's disease maps between D12S78 and D12S79.
AB  - Darier's disease is a dominantly inherited skin disorder in which there is
      abnormal adhesion between keratinocytes. We and others have recently mapped the
      disease gene to chromosome 12q23-q 24.1. In the present study we have established
      that the disease gene lies between the loci D12S78 and D12S79 which are 12cM
      apart. We have also obtained direct evidence that the disease is unlikely to
      result from a mutation in one of the members of the keratin gene cluster on
      chromosome 12q.

PMID- 7512860
TI  - Identification of six novel mutations in the CFTR gene of patients from Bulgaria
      by screening the twenty seven exons and exon/intron boundaries using DGGE and
      direct DNA sequencing.
AB  - The CFTR gene, in which more than 300 mutations have been described, displays a
      spectrum of mutations which varies according to ethnic and geographic origin of
      patients. In this paper we report an exhaustive study of the 27 exons and
      exon/intron boundaries of a sample of 35 CF patients from Bulgaria which is
      situated in the south east of Europe. We have used denaturing gradient gel
      electrophoresis assay followed by DNA sequencing and we report the identification
      of six previously undescribed CFTR alleles.

PMID- 7512863
TI  - [Specific parent training in alalia. 1: Introduction and presentation of the
      seminar concept].
AB  - Developmental aphasia is the most severe form of speech retardation and needs
      therapeutic intervention. The young age of these children (< 3 years) makes
      therapy difficult. A specified speech therapy is not possible at this age.
      Intensive stimulation of verbal communication by the parents is necessary.
      Therefore we developed a specialized training program for parents. This
      preparation is very useful for later therapy and should prevent disturbance of
      interaction between parents and child. We will present our concept.

PMID- 7512861
TI  - Maternal imprinting of human SNRPN, a gene deleted in Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS), a human neuroendocrine disorder, is associated with
      deficiencies of paternal chromosome 15q12. Small nuclear ribonucleoprotein
      polypeptide N (SNRPN) is the first expressed gene identified in the PWS
      critically deleted region. Following our demonstration that the murine homologue
      of SNRPN is imprinted, we have characterized a sequence polymorphism within
      expressed portions of human SNRPN and show that human SNRPN is monoallelically
      expressed in fetal brain and heart and in adult brain. Analysis of maternal DNA
      and SNRPN cDNA confirmed that the maternal allele of SNRPN is not expressed in
      fetal brain and heart. Maternal imprinting of SNRPN supports the hypothesis that
      paternal absence of SNRPN is responsible for the PWS phenotype.

PMID- 7512862
TI  - Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK).
AB  - We have isolated the gene for human type I keratin 9 (KRT9) and localised it to
      chromosome 17q21. Patients with epidermolytic palmoplantar keratoderma (EPPK), an
      autosomal dominant skin disease, were investigated. Three KRT9 mutations, N160K,
      R162Q, and R162W, were identified. All the mutations are in the highly conserved
      coil 1A of the rod domain, thought to be important for heterodimerisation. R162W
      was detected in five unrelated families and affects the corresponding residue in
      the keratin 14 and keratin 10 genes that is also altered in cases of
      epidermolysis bullosa simplex and generalised epidermolytic hyperkeratosis,
      respectively. These findings provide further evidence that mutations in keratin
      genes may cause epidermolysis and hyperkeratosis and that hyperkeratosis of palms
      and soles may be caused by different mutations in the KRT9 gene.

PMID- 7512864
TI  - [Specific parent training in alalia. 2: Study of experiences of parents in the
      seminar].
AB  - Specified training for parents of children with developmental aphasia has been
      offered for several years. We want to guide the parents to a controlled
      stimulation of speech at home. We asked the former participants about their
      experiences with this training program. We also studied the realization of the
      program by parents in everyday life before their children started therapy. The
      experiences were mainly considered positive, realizing the program did not
      present difficulties.

PMID- 7512866
TI  - Immunohistochemical and ultrastructural study of skull base chordomas.
AB  - Eight chordomas were studied by using specific antibodies against cytokeratin,
      vimentin, desmin, type II collagen, S-100 protein, epithelial membrane antigen
      (EMA), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). One
      chondrosarcoma was included as a representative of chondroid tumors. All
      chordomas were positively stained for epithelial markers (cytokeratin and EMA),
      whereas the chondrosarcoma was not. All chordomas and the chondrosarcoma
      expressed vimentin, type II collagen and S-100 protein. Oncofetal antigens (CEA
      and AFP) and desmin were found in five (63%) chordomas, whereas these antigens
      were not found in the chondrosarcoma. Ultrastructurally the chordoma cells showed
      junctional complexes, microvillous projections and basal lamina-like structures
      alongside the tumor cells, whereas the tumor cells of the chondrosarcoma had
      neither junctions and microvillous projections, nor basement membrane. The
      present study demonstrates the utility of these tumor markers and ultrastructural
      features in the differential diagnosis of chordomas and tumors with similar
      histologic patterns such as chondrosarcomas.

PMID- 7512867
TI  - Immunohistochemical differential diagnosis of benign cysts in the central nervous
      system.
AB  - This report concerns the immunohistochemical characterization of 6 cases of thin
      walled cysts in the central nervous system (enterogenous cyst, paraphyseal
      neuroepithelial cyst, Rathke's cleft cyst and arachnoid cyst). Antibodies to
      glial fibrillary acidic protein (GFAP), S-100 protein, epithelial membrane
      antigen (EMA), carcinoembryonic antigen (CEA), keratin (KER) and vimentin (VIM)
      were used. The enterogenous cyst was positive for KER, EMA and CEA. The
      neuroepithelial cyst of paraphyseal origin was positive for KER and S-100. The
      three Rathke's cleft cysts were positive for KER and EMA, but negative for S-100
      and CEA, and the arachnoid cyst was positive for EMA and VIM. A unified concept
      and classification of the types of cysts studied based on immunohistochemical
      assays are proposed.

PMID- 7512865
TI  - Immunohistochemical and electron microscopic studies on intracranial chordomas:
      difference between typical chordomas and chondroid chordomas.
AB  - Immunohistochemical and electron microscopic studies were carried out on 9 cases
      of intracranial chordomas. Three of them were typical chordomas and 6 were
      chondroid chordomas. Immunohistochemically, both typical chordomas and chondroid
      chordomas were positively stained for cytokeratin and epithelial membrane
      antigen. Chondroid chordomas were stained for vimentin with moderate intensity
      whereas typical chordomas were only slightly stained. In comparison to typical
      chordomas, the chondroid chordomas had relatively few desmosomes and intermediate
      filaments. These findings suggest that intracranial chordomas are of mixed
      epithelial-mesenchymal nature, and that chondroid chordomas have a predominant
      mesenchymal character as compared to typical chordomas.

PMID- 7512869
TI  - Are point mutations or DNA rearrangements responsible for the restriction
      fragment length polymorphisms that are used to type bacteria?
AB  - Restriction fragment length polymorphisms (RFLPs) detected in total DNA or in
      rRNA genes are widely used to differentiate strains of bacteria. The changes
      accounting for these polymorphisms and the extent of genomic difference that they
      reflect are generally unknown. In this report, several methods have been used to
      examine the DNA differences between nine Enterococcus faecalis isolates.
      Restriction fragments from total DNA and from rRNA genes were compared between
      isolates using four and five different restriction enzymes, respectively. The
      proportion of polymorphic fragments detected was greater with total DNA than with
      rRNA gene patterns, but depended considerably on the restriction enzyme used. DNA
      changes underlying nine RFLPs were investigated by using the polymorphic
      fragments as probes to test for alteration in the position of recognition sites
      of other enzymes. Two polymorphisms were deduced to result from point mutation in
      a restriction site. Six were judged to result from DNA rearrangements, five of
      which involved deletion/insertion of the entire probe fragment. The results
      demonstrate that DNA rearrangements may be responsible for a high proportion of
      RFLPs used to differentiate and type strains of bacteria. While this does not
      limit the utility of such methods, it does preclude calculation of overall DNA
      sequence conservation from similarities in restriction pattern between isolates.
      DNA sequence determination of the 16S-23S rRNA intergenic spacer of three
      isolates revealed minimal base substitutions (less than 1%), suggesting that
      overall sequence divergence between the isolates may be low.

PMID- 7512870
TI  - Localization of antigenic domains on the major subunits of Bordetella pertussis
      serotype 2 and 3 fimbriae.
AB  - Antibody-binding domains on the major subunits of Bordetella pertussis serotype 2
      (Fim2) and 3 fimbriae (Fim3) have been identified using synthetic peptides which
      were screened for recognition by anti-protein monoclonal antibodies (mAbs). The
      presence of non-contiguous fimbrial epitopes was demonstrated by both anti-Fim2
      and anti-Fim3 mAbs, several of which recognized at least two peptides that were
      discontinuous in the amino acid sequence of the corresponding subunits. The
      specificity of one mAb, 51/24, directed against Fim2, was investigated by
      replacement-set analysis of a 10-residue peptide, and revealed that antibody
      binding to the peptide was dependent on the sequence N94PQ96 which is non
      conserved in Fim3. Furthermore, proline at residue 95 was found to be essential
      for mAb 51/24 binding. The specific anti-Fim3 mAb, AG3A, was found to recognize
      the 10-residue carboxy-terminal peptide from both Fim3 and, unexpectedly, from
      Fim2. This result suggests that mAb AG3A serospecificity at the protein level is
      determined by a conformational constraint which prevents mAb AG3A binding to the
      Fim2 C-terminal domain. Several free peptides containing amino acid residues
      which comprise part of the Fim2 and Fim3 epitopic domains were prepared as
      immunogens. One of these peptides was immunogenic in the mouse, indicating the
      location of a T-helper cell epitope within the peptide sequence, and induced a
      strong anti-peptide antibody response. The other peptides each required
      immunization as a conjugate with a carrier protein for anti-peptide antibody
      stimulation. All four anti-peptide antibody preparations only weakly recognized
      fimbriae-coated ELISA plates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512868
TI  - Nucleotide sequence and secondary structures of precursor 16S rRNA of slow
      growing mycobacteria.
AB  - Slow-growing mycobacteria have a single ribosomal RNA (rrn) operon, with the
      genes for 16S, 23S and 5s rRNA being present in that order. The transcription
      start site of the rrn operon of Mycobacterium tuberculosis was identified in
      Escherichia coli. PCR methodology was used to amplify parts of the rrn operon,
      namely the leader region and the spacer-1 region separating the 16S rRNA and 23S
      rRNA genes of Mycobacterium avium, Mycobacterium paratuberculosis, Mycobacterium
      intracellulare, 'Mycobacterium lufu', Mycobacterium simiae and Mycobacterium
      marinum. The amplified DNA was sequenced. The sequence data, together with those
      obtained previously for Mycobacterium leprae and M. tuberculosis, were used to
      identify putative antitermination signals and RNase III processing sites within
      the leader region. Notable features include a highly conserved Box B element and
      a sequence of 31 nucleotides which is common to all eight slow-growers which were
      scrutinized. A secondary structure for mycobacterial precursor-16S rRNA was
      devised, based on sequence homologies and homologous nucleotide substitutions.
      The 18 nucleotides at the 5'-end of spacer-1 have the capacity of binding
      sequences close to the 5'- and 3'-ends of mature 16S rRNA, suggesting that
      secondary structure is important to the maturation process. All the slow-growers,
      including M. leprae, conform to the same scheme of secondary structure. The
      scheme proposed for M. tuberculosis is a variant of the main theme. The leader
      and spacer sequences may prove a useful supplement to 16S rRNA sequences in
      establishing phylogenetic relationships between very closely related species. 'M.
      lufu' appears to be a close relative of M. intracellulare.

PMID- 7512871
TI  - Survival of Staphylococcus aureus in lakewater monitored by flow cytometry.
AB  - The ability of flow cytometry to detect and enumerate viable bacteria during
      survival in a lakewater microcosm was assessed using Staphylococcus aureus as a
      model organism. Counts of colony-forming units (c.f.u.) on nutrient agar were not
      significantly different from those obtained by flow cytometric detection of
      rhodamine 123 stained bacteria and there was no evidence for a viable but
      nonculturable state using these methods. However c.f.u. were significantly lower
      when estimated using mannitol salts agar compared with nutrient agar. S. aureus
      was also enumerated immunofluorescently after staining with FITC-IgG. There was
      no significant difference between the population estimated immunofluorescently
      and by acridine orange direct counting, and unlike estimations of viability, only
      slight reductions in total cell numbers were observed. Changes in the protein and
      nucleic acid content of S. aureus during survival were also measured by flow
      cytometry to investigate any potential heterogeneity arising within the starved
      population. Flow cytometric determinations were found to correlate significantly
      with their respective chemical determinations. These results demonstrate the
      ability of flow cytometry to detect viable bacteria during starvation and to
      study changes in macromolecular content. They also illustrate the importance of
      using appropriate methods for the detection of viable bacteria in environmental
      samples.

PMID- 7512872
TI  - Escherichia coli K12 regains its O antigen.
AB  - Extant Escherichia coli K12 strains are phenotypically rough, their
      lipopolysaccharide having a complete core structure, but no O antigen. We used
      DNA hybridization and DNA sequencing to show that the rough phenotype of this
      strain is due to the presence of one of two independent mutations in the rfb gene
      cluster. The rfb-50 mutation, consisting of an IS5 insertion at the downstream
      end of rfb, is present in strain EMG2, which is representative of most K12
      derivatives. The rfb-51 mutation is a deletion at the upstream end of rfb, and
      was found in strain WG1. A gene cloned from strain WG1 could complement the rfb
      50 mutation in strain EMG2, and the complemented strain produced O antigen which
      was typed as O16 with cross reaction to O17.

PMID- 7512873
TI  - Induction of alloantigen-specific cytotoxic and suppressor activities of
      lymphocytes by intravenous immunization of mice when donor and recipient differ
      in class II MHC molecule.
AB  - Induction of alloantigen-specific cytotoxic and suppressor activities of
      lymphocytes was studied upon intravenous immunization of recipients C57Bl/6 with
      B6.C-H-2bm12 donor's splenocytes irradiated with 2000 rads and introduced in a
      dose of 9 x 10(7). A possibility was shown to induce a specific cytotoxic and
      suppressor activities may be induced individually. We studied a possibility to
      detect the suppressor activity of immune splenocytes in the reaction of skin
      graft rejection. No significant prolongation of the B6.C-H-2bm12 skin graft life
      was noted in C57Bl/6 recipients, irradiated with 2000 rads, under the action of
      adoptive transfer of the immune syngenic splenocytes in comparison with the
      grafts life in recipients received the adoptive transfer of intact splenocytes.

PMID- 7512874
TI  - Pancreatic islet purification using bovine serum albumin: the importance of
      density gradient temperature and osmolality.
AB  - Euro-Ficoll and bovine serum albumin (BSA) are two of the most commonly used
      density gradient media for the purification of pancreatic islets. Euro-Ficoll is
      based upon Euro-Collins, a cold storage medium, and must, therefore, be used at 4
      degrees C. The ionic composition of BSA, however, is likely to contribute to
      hypothermic cellular swelling, and this may influence the efficiency of islet
      purification using this medium at 4 degrees C. Experience in this laboratory also
      suggested that batch-to-batch variation in islet purity using BSA was related to
      differences in BSA osmolality. The aim of this study was to assess the effect of
      gradient medium temperature and osmolality on the purification of human and
      porcine islets using BSA. Pancreata were collagenase-digested, and islets were
      purified on continuous linear density gradients of BSA. The distribution of
      insulin and amylase in each gradient was assayed, and used to calculate the
      median density of islets and exocrine tissue, and the efficiency of islet
      purification (% amylase contamination at a fixed insulin yield), using: 1)
      gradient osmolalities of 300, 400, and 500 mOsm/kg H2O (seven porcine pancreata),
      and 2) gradients at 4 degrees C and at 22 degrees C (eight human and seven
      porcine pancreata). Increase in density gradient osmolality produced increases in
      porcine exocrine tissue density which exceeded changes in islet density,
      resulting in improved islet purity, maximal at a BSA osmolality of 400 mOsm/kg
      H2O. For human pancreata there was no significant change in pancreatic tissue
      densities nor islet purity with temperature.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7512875
TI  - Effect of FK506 and anti-CD4 therapy on fetal pig pancreas xenografts and host
      lymphoid cells in nod/Lt, CBA, and BALB/c mice.
AB  - Varying doses of FK506, and a cell-depleting anti-CD4 monoclonal antibody, GK1.5,
      were tested as either monotherapy or in combination for their effect on the
      survival of renal subcapsular xenografts of organ-cultured fetal pig pancreas in
      three strains of mice. Subcutaneous injections of FK506 at 4.0 mg/kg/day for 28 d
      prevented graft rejection to day 35 posttransplantation (i.e., 7 days after
      cessation of treatment in NOD/Lt, and CBA mice) while BALB/c mice had intact
      grafts at 28 days. Lower doses were less effective and immunosuppression was less
      effective in NOD mice than in the other strains. Even 2.0 mg/kg/day of FK506
      prevented rejection in CBA mice until day 35, but not in NOD/Lt mice. GK1.5 alone
      did not prevent rejection in NOD/Lt mice but when a low dose of FK506 (2.0
      mg/day) was added, the grafts were present, essentially intact, at 35 days. There
      were no obvious toxic effects of FK506 in NOD/Lt and CBA mice. With FK506
      treatment there was no significant difference in absolute numbers of total
      leucocytes or lymphocytes in peripheral blood and spleen, but there was a
      decrease in thymus cellularity. Flow cytometric analysis of lymphocyte subsets in
      blood and spleen also showed no significant differences, but in the thymus the
      percentage of immature CD4/CD8 "double positive" cells increased while the more
      mature CD3"high", and CD4 or CD8 "single-positive" cells decreased. Thus,
      prolonged discordant xenograft survival in mice is possible and the use of two
      agents that act on different parts of the immune system allows a reduction in the
      dose of FK506 to safe levels.

PMID- 7512877
TI  - Induction of donor specific unresponsiveness in rat islet allografts by
      intraportal grafting and FK506.

PMID- 7512876
TI  - Donor-specific unresponsiveness induced by intraportal grafting and FK506 in rat
      islet allografts: importance of low temperature culture and transplant site on
      induction and maintenance.
AB  - Previously we demonstrated prolongation of islet allograft survival in rat by
      administration of FK506 to the recipients. The purpose of the present study was
      to determine whether specific immune unresponsiveness had been induced and to
      determine the effects of low temperature culture of donor islets as well as the
      transplant site on the induction of immune unresponsiveness. At 90 days after
      transplantation, normoglycemic recipients bearing functional intrahepatic grafts
      were made diabetic again with streptozotocin (STZ) and donor specific or third
      party islets were transplanted either into the liver or beneath the kidney
      capsule. When fresh islets were used as donors in initial transplantation in
      conjunction with FK506, intrahepatic re-transplants of fresh islets from the
      donor-specific strain in the absence of FK506 maintained normoglycemia for more
      than 60 days, while third party transplants (n = 3) were rejected within 1 wk. In
      contrast to intrahepatic regrafts, all the renal subcapsular regrafts from the
      donor-specific strain (n = 3) were rejected with mean survival time of 12.7 +/-
      6.4 days. When cultured (24 degrees C, 7 days) islets were used for initial
      transplantation in conjunction with FK506, re-transplants of fresh or cultured
      islets from the donor specific strain beneath the kidney capsule maintained
      normoglycemic in 3 out of 6 or all (n = 4) of the recipients, respectively.
      Cultured third party regrafts beneath the kidney capsule (n = 2) were rejected at
      9 days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512878
TI  - Isolation and culture of brain endothelial cells and establishment of in vitro
      blood-brain barrier model.

PMID- 7512881
TI  - Expression of growth factor receptors on human melanoma cells: comparison of
      modulating effects of interferons and retinoids.
AB  - Autocrine and paracrine growth factors are important mediators in malignant
      transformation. Interferons (IFN) and retinoids (RX) are well-known
      differentiative and immunomodulating agents with effects on subsets of different
      human tumors including malignant melanoma. In this study, we examined the
      modulating effects of three IFN and seven different RX on human melanoma cell
      lines regarding growth factor receptor expression. Growth factor receptor
      expression, including PDGF-R, NGF-R, EGF-R, IR, IGF-I-R, TFR and c-kit, was
      studied by immunohistochemistry and FACSscan analysis. Both groups of substances
      modulated the expression of some growth factor receptors. Upregulation of PDGF-R
      was seen after treatment with IFN as well as with RX. In contrast, EGF-R was
      found to be downregulated in two EGF-R-positive cell lines by IFN and, on the
      other hand, induced by RX in two EGF-R-negative cell lines. The expression of NGF
      R was modulated ambiguously by these substances but demonstrated a cell line
      specificity in the different melanoma cell lines tested. Additionally, some of
      the tested growth factor receptors were not markedly changed regarding their
      expression by treatment with IFN and RX (IR, IGF-I-R, c-kit, TFR).

PMID- 7512880
TI  - Production of multiple cytokines by cultured human melanomas.
AB  - We screened a panel of 8 primary and 21 metastatic melanoma cell lines for
      constitutive secretion of cytokines. Melanomas expressed bioactivity for TGF-beta
      (8/25 lines) and IFN (7/12), but not IL-2. Immunoassays detected IL-1 alpha
      (4/25), IL-1 beta (12/25), IL-6 (13/29), IL-8 (29/29), TGF-beta 2 (5/12) and GM
      CSF (11/29), but not IL-3, IL-4, TNF-alpha, or IFN-gamma. There was no
      preferential association of cytokine production with cells cultured from primary
      versus metastatic disease, and only IL-8 was produced by all lines tested. These
      data demonstrate that cultured melanomas produce a variety of cytokines which are
      potentially capable of influencing tumor growth in vivo.

PMID- 7512879
TI  - 5-azacytidine produces differential undercondensation of alpha, beta and
      classical human satellite DNAs.
AB  - Fluorescence in situ hybridization employing human alphoid, beta and classical
      satellite DNA probes was performed on 5-azacytidine treated and untreated
      chromosomes obtained from human lymphocytes. The individual used in this study
      presented a polymorphism of constitutive heterochromatin of chromosomes 1 and 9
      as revealed by in situ digestion with the restriction endonuclease Alul. Neither
      the alphoid nor the beta satellite DNA domains were susceptible to condensation
      inhibition by 5-azacytidine. Only the classical satellite localized on chromosome
      9 was affected. The constitutive heterochromatin size polymorphism was shown to
      depend mainly on variations of the classical satellite DNA domain. Therefore,
      condensation-inhibition, as a phenomenon which may modify the natural folding of
      the chromatin fibre, regionally affects human constitutive heterochromatin and
      seems to be dependent on the heterochromatic family.

PMID- 7512882
TI  - Tenascin and arthritis.

PMID- 7512883
TI  - The role of lasers in urology.

PMID- 7512884
TI  - [How to treat patients with non-life-threatening arrhythmia symptoms].

PMID- 7512885
TI  - Detection of insulin-like growth factor binding proteins (IGFBPs) by ligand
      blotting in breast cancer tissues.
AB  - Eighty breast cancer specimens were examined for insulin-like growth factor
      binding protein (IGFBP) expression by ligand blotting. Five distinct IGFBP
      species were found: a doublet at 48 and 44 kDa was IGFBP-3, the 34-kDa band was
      IGFBP-2, and a band at 24 kDa was IGFBP-4. A 32-kDa band was compatible with the
      migration position reported for IGFBP-5. IGFBP-3 was inversely correlated with ER
      expression, while IGFBP-4 was positively correlated with both ER and PgR. IGFBP-4
      was also inversely correlated with S-phase fraction. Thus, IGFBP expression
      correlates with other parameters of breast cancer biology and may play a role in
      regulating tumor growth.

PMID- 7512886
TI  - Enzymatic tumour markers in ovarian cancer: a multiparametric study.
AB  - The serum concentration of some enzymes, namely placental alkaline phosphatase,
      lactate dehydrogenase, 5' nucleotidase and amylase, was determined by
      commercially available kit in 50 ovarian cancer patients and 31 patients with
      benign gynaecological disease before initiation of any treatment. The values were
      compared with those of 30 healthy women. Multivariate analysis showed a
      statistically significant difference between healthy women and ovarian cancer
      patients. These results indicate that by using discriminating function of the
      above four enzyme variables it is possible to screen ovarian cancer in outpatient
      obstetric and gynaecological clinics (sensitivity 96%, specificity 83.3%,
      relative risk 11.7). Hence this system can serve as a suitable marker for ovarian
      cancer.

PMID- 7512889
TI  - Genetic linkage of proteolipid protein (PLP) and thyroxine-binding globulin (TBG)
      on the ovine X chromosome.
AB  - Restriction fragment length polymorphisms (RFLPs) demonstrating X-linked
      inheritance have been identified for proteolipid protein (PLP) and thyroxine
      binding globulin (TBG) in sheep. Genetic linkage between ovine PLP and TBG was
      examined in a three-generation flock containing 122 individuals. Significant
      linkage between the loci was observed with a combined lod score of 7.48 at a
      recombination fraction of 5 cM.

PMID- 7512888
TI  - Natural-killer-stimulatory effect of combined low-dose interleukin-2 and
      interferon beta in hairy-cell leukemia patients.
AB  - The association of low doses of interleukin-2 (IL-2; 5 IU/ml) and interferon beta
      (IFN beta; 10 IU/ml) induced an additive or synergic stimulatory effect on
      natural killer (NK) activity (32%) in peripheral blood samples from hairy-cell
      leukemia patients, both those with active disease and those in remission. The
      synergic NK stimulatory effect was more commonly found in samples from patients
      with active disease, while the additive effect was more frequent in the patients
      in remission. The IL-2/IFN beta combination provoked a nonadditive nonsynergic NK
      stimulatory effect in a further 19.8% samples. The targets of the IL-2/IFN beta
      combination were typical NK cells, as shown by the fact that there was increased
      cytotoxicity (synergic, additive or nonadditive nonsynergic) against the K562,
      but not the Daudi cell line in peripheral blood mononuclear cell samples treated
      with the combination of the two cytokines. When CD16+/CD56+ or CD57+/CD16+/CD56+
      cells were removed, the NK-stimulatory effect was lost. The fact that the NK-cell
      enhancing activity of the IL-2/IFN beta combination was reduced when Percoll
      fractions 2 and 3 were used, but still persisted in 66% of tests, may have been
      due to cytotoxicity being higher in the untreated fractions 2 and 3 than in the
      untreated unfractionated samples. One of the factors responsible for the NK
      stimulatory effect appears to be the capacity of the IL-2/IFN beta combination to
      trigger an increase in IFN gamma synthesis. If similar experiments give like
      results in samples from patients suffering from other B-cell lymphoproliferative,
      or HIV-associated disorders, all of which are characterized by a deficiency in NK
      activity, it should be possible to use low-dose IL-2/IFN beta to treat these
      disorders and, perhaps, residual neoplastic disease without exposing the patient
      to undue toxicity. Further, by testing other combinations one should be able to
      identify the lowest IL-2 and IFN beta doses that would effectively boost the
      additive or synergic effect in a greater number of cases.

PMID- 7512887
TI  - Chimeric murine-human antibodies directed against folate binding receptor are
      efficient mediators of ovarian carcinoma cell killing.
AB  - The MOv18 (gamma 1, kappa) and MOv19 (gamma 2a, kappa) murine monoclonal
      antibodies (MAbs) recognize different epitopes on the human folate binding
      receptor which is overexpressed on 90% of nonmucinous epithelial ovarian tumors.
      A chimeric murine-human (human gamma 1, kappa) version of both antibodies was
      constructed and expressed. The genes encoding the murine heavy and light chain
      variable regions of the MOv18 and MOv19 MAbs were cloned from the parental
      hybridomas, fused with genes encoding the human heavy (gamma 1) and light (kappa)
      chain constant regions, respectively, and expressed in the SP2/0 murine myeloma
      cell line. Using human peripheral blood mononuclear cells as effector cells and
      conditions that provide for maximum lysis (effector target = 50:1, saturating
      antibody concentration), the murine MOv18 MAb (IgG1) mediated variable levels of
      specific cytolysis of the target ovarian cancer cell line IGROV1. In contrast,
      the chimeric MOv18 MAb mediated higher and more consistent lysis even at a 10-100
      fold lower antibody concentration. The murine MOv19 MAb (IgG2a) mediated specific
      lysis of IGROV1 cells, and the chimeric version of this antibody mediated an
      amount of lysis at least equal to that mediated by its murine counterpart. A
      comparison of the ED50 values obtained for the murine MOv19 and chimeric MOv19
      antibodies indicates that the chimeric MOv19 MAb was 3 to 10 times more potent
      than the murine MOv19 antibody. In addition, the ED50 values obtained for the
      chimeric MOv18 and chimeric MOv19 MAbs were similar, indicating that these MAbs
      are equally potent. The level of maximal lysis obtained was dependent on the
      number of target molecules/cell; the same high level of lysis mediated by cMOv18,
      MOv19, and cMOv19 was observed with both IGROV1 and OvCA432 target cells.
      However, only low levels of lysis were obtained when the SW626 cell line, which
      expresses 1 x 10(4) folate binding protein sites/cell, was used as a target. An
      equimolar mixture of the chimeric MOv18 and MOv19 MAbs was no more effective in
      the mediation of lysis than an equivalent amount of either chimeric MAb alone.
      These data suggest that the folate binding receptor is expressed on IGROV1 cells
      at a density sufficient to provide for optimal levels of antibody-mediated lysis
      using a single chimeric antibody directed at the folate binding receptor.

PMID- 7512890
TI  - Assignment of the human gene for the water channel of renal collecting duct
      Aquaporin 2 (AQP2) to chromosome 12 region q12-->q13.
AB  - The chromosomal localization of the gene encoding Aquaporin 2 (previously called
      WCH-CD), which acts as a water channel in the collecting tubules of the kidney,
      was determined. Southern blot hybridizations of chromosomal DNA from a panel of
      25 different human-rodent hybrid cell lines assigned AQP2 to the q-arm of human
      chromosome 12. Additionally, in situ hybridization on R-banded metaphase
      chromosomes localized AQP2 to the q12-->q13 region of this chromosome.

PMID- 7512891
TI  - Sensitive method for measuring apoptosis and cell surface phenotype in human
      thymocytes by flow cytometry.
AB  - A rapid, gentle, and sensitive method for quantification of cells undergoing
      apoptosis is presented. The method allows the simultaneous determination of dual
      color cell surface immunofluorescence. Cells are stained for 7 min with the vital
      dye Hoechst 33342 (HO342) for identification of live and apoptotic cells. 7-amino
      actinomycin D (7-AAD) is added to distinguish cells that have lost membrane
      integrity from apoptotic and live cells. Due to its spectral properties 7-AAD can
      be utilized on cells that are dual-surface labelled with fluorescein
      isothiocyanate (FITC) and phycoerythrin (PE). The value of the method is
      demonstrated on human thymocytes, which constitutively undergo programmed cell
      death and which show an increase in the rate of apoptosis after exposure to the
      glucocorticoid dexamethasone (DEX). Vital staining with HO342 permits earlier
      detection of apoptotic changes compared to a staining technique in which cells
      are treated with a hypotonic citrate solution containing propidium iodide (PI)
      and the apoptotic cells are represented in a hypodiploid, "sub-G1" peak. The
      HO342/7-AAD method may be particularly applicable to studies of programmed cell
      death in cells in which DNA fragmentation is difficult to detect by decreased DNA
      stainability.

PMID- 7512895
TI  - [Prostate carcinoma].

PMID- 7512894
TI  - Streptavidin-tricolor is a reliable marker for nonviable cells subjected to
      permeabilization or fixation.
AB  - Cell death is normally accompanied by loss of integrity of the cell membrane.
      Concomitant loss of osmotic pressure and permeability for DNA binding dyes like
      propidium iodide make it possible to distinguish viable from nonviable cells.
      However, after permeabilization for intracellular staining or after fixation of
      the cells, we find that propidium iodide leaks out of nonviable cells and is
      transferred to formerly viable cells. Cell size cannot be used for examining
      viability in permeabilized or heterogeneous cell populations. Here we show that
      streptavidin-tricolor enters specifically and irreversibly into dead cells, and
      is not transferred to formerly viable cells after fixation or permeabilization.
      Therefore, streptavidin-tricolor can be a useful dead-cell marker in experimental
      situations where conventional methods fail to distinguish between viable and
      nonviable cells.

PMID- 7512893
TI  - Improved flow-cytometric detection of low P-glycoprotein expression in leukaemic
      blasts by histogram subtraction analysis.
AB  - Expression of the drug efflux pump P-glycoprotein (PGP) was determined by flow
      cytometry in human lung cancer cell lines and in leukaemic blasts derived from 60
      patients with acute myeloid leukaemia (AML). Cells from the PGP-negative parent
      cell line H69/P and the multidrug resistant (MDR)-variant H69/LX4 could be
      clearly distinguished by immunostaining with the anti-PGP monoclonal antibody
      MRK16. In leukaemic blasts, the differences in fluorescence intensities between
      samples incubated with the idiotypic nonspecific (control sample) and specific
      antibody (test sample) were small, resulting in nondisjunct distributions. Only
      in a few leukaemia specimens were PGP-expressing cells detectable by simple
      subtraction of histograms using a threshold. Therefore, an improved histogram
      subtraction analysis, based on curve fitting and a statistical test, was applied
      to distinguish antigen-positive from antigen-negative cells. Moreover, a
      multiparametric staining procedure employing propidium iodide (PI) and Hoechst
      33342 was used to reduce staining artefacts. By this approach, leukaemic cells
      with low expression of PGP were detected in 39 out of 60 cases. Subpopulations
      with strong PGP expression, resulting in disjunct fluorescence distributions,
      were not observed. Only in 5 out of 60 specimens were PGP expressing cells
      detected by a conventional subtraction of histograms using a threshold.
      Comparison of data obtained with or without the multiparametric gating procedure
      indicated that the increase in sensitivity was mainly due to the application of
      the data analysis. However, exclusion of cell debris using PI and Hoechst
      staining properties reduced the deviation of data from mean values. No relation
      between PGP expression and cell cycle position was observed in either cell lines
      or in leukaemic blasts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512892
TI  - Single UV excitation of Hoechst 33342 and ethidium bromide for simultaneous cell
      cycle analysis and viability determinations on in vitro cultures of murine B
      lymphocytes.
AB  - Assessment of DNA content by flow cytometry has largely depended on staining
      techniques which do not permit exclusion of dead cells from the data set. During
      studies of B cell activation in vitro, the large number of nonviable cells
      greatly affects the cell cycle distribution and thus the accurate evaluation of
      proliferation flow cytometry. This report describes the development of two dual
      staining techniques which use Hoechst 33342 and ethidium bromide excited by a
      single UV source to eliminate dead cells from the DNA histogram of the viable
      cells in murine B cell cultures. Hoechst 33342 and 0.62 micrograms/ml of ethidium
      bromide permit the evaluation of cell cycle distributions on the viable cells
      with a ratio gate. The combination of Hoechst 33342 and 6.2 micrograms/ml
      ethidium bromide results in the resolution of the two populations due to
      fluorescence energy transfer with a single PMT. Using this technique we
      demonstrated the simultaneous determination of DNA and RNA content on viable
      cells using only two PMTs. Both these techniques can be performed on either a
      laser or an arc lamp flow cytometer where CVs of less than 7% and as low as 3.2%
      are normally achieved. Determination of the S phase using these techniques
      produces a high correlation with DNA synthesis determined by radiolabeled
      precursor determination. These techniques permit the use of flow cytometry to
      determine proliferation during B cell activation.

PMID- 7512896
TI  - Novel tenascin variants with a distinctive pattern of expression in the avian
      embryo.
AB  - Previous studies have shown that several forms of the glycoprotein tenascin are
      present in the embryonic extracellular matrix. These forms are the result of
      alternative splicing, which generates tenascin variants with different numbers of
      fibronectin type III repeats. We have used degenerate primers and PCR to isolate
      a novel tenascin exon from an avian genomic library. Genomic clones contained a
      sequence encoding a fibronectin type III repeat that corresponds to repeat 'C'
      from the variable domain of human tenascin. To demonstrate that tenascin
      containing repeat 'C' is actually synthesized by avian cells, a monospecific
      antiserum was raised against a repeat 'C' fusion protein. This antiserum
      recognized a novel high-molecular-weight variant on immunoblots of tenascin
      isolated from chicken embryo fibroblast-conditioned medium, and stained tendons
      on frozen sections of chicken embryos. A cDNA probe specific for mRNA encoding
      repeat 'C' was used for in situ hybridization. This probe hybridized in a subset
      of the embryonic tissues labelled with a universal tenascin probe, including
      tendons, ligaments and mesenchyme at sites of epithelial-mesenchymal
      interactions. Finally, we provide evidence that additional fibronectin type III
      repeats, one corresponding to a recently discovered human repeat as well as one
      entirely novel sequence, also exists in chicken tenascin mRNA. These data
      indicate that tenascin is present in the embryonic matrix in a multitude of forms
      and that these forms have distinctive distributions that may reflect more than
      one function for tenascin in development.

PMID- 7512897
TI  - Tenascin is induced at implantation sites in the mouse uterus and interferes with
      epithelial cell adhesion.
AB  - Expression of tenascin, an extracellular matrix protein associated with
      morphogenetic events and altered states of cellular adhesion, was examined in
      mouse uterus during the peri-implantation period. A uniform low level expression
      of tenascin was detected in stromal extracellular matrix during the estrous cycle
      and days 1 through 4 of early pregnancy. During the period of blastocyst
      attachment (day 4.5), an intense deposition of tenascin fibrils was located in
      the extracellular matrix of stroma immediately subjacent to the uterine
      epithelium surrounding the attaching blastocyst. This localized intensity of
      tenascin expression was both spatially and temporally restricted. By day 5.5,
      differentiation of stroma in the immediate area around the embryo to form the
      primary decidual zone was accompanied by a reduced amount of tenascin expression
      in the form of fragmented fibrils. Tenascin also could be induced by an
      artificial stimulus in uterine stroma of mice that had been hormonally prepared
      for implantation. The ability of artificial stimuli to induce tenascin expression
      suggested that the tenascin-inducing signals were derived from uterine cells,
      presumably lumenal epithelium, rather than embryonic cells. Consistent with this,
      conditioned medium from primary cultures of uterine epithelium was found to
      induce tenascin expression (2- to 4-fold) in isolated uterine stroma. Artificial
      stimuli generated a temporal pattern of tenascin expression similar to that
      observed during early pregnancy; however, in the artificially induced model,
      tenascin was induced in stroma immediately subjacent to lumenal epithelium along
      the entire length of the uterus. Purified tenascin and a recombinant tenascin
      fragment consisting of alternatively spliced fibronectin type III repeats,
      interfered with maintenance of uterine epithelial cell adhesion to Matrigel. In
      contrast, other recombinant tenascin fragments or fibronectin had no effect in
      this regard. Tenascin had no effect on adhesion of uterine stroma. Collectively,
      these results suggest that stimulation of TN expression in stromal extracellular
      matrix in vivo occurs via hormonally regulated, epithelial-mesenchymal
      interactions and serves as an early marker for uterine receptivity and the
      attachment phase of implantation. Furthermore, tenascin may facilitate embryo
      penetration by disrupting uterine epithelial cell adhesion to underlying basal
      lamina.

PMID- 7512898
TI  - Long- versus short-acting beta 2-agonists. Implications for drug therapy.

PMID- 7512902
TI  - Genital herpes. A guide to pharmacological therapy.
AB  - The pharmacological therapy for genital herpes simplex virus (HSV) infection
      remains dominated by aciclovir, although a number of related compounds are
      currently under investigation. Recommended treatment for initial genital HSV
      infection is oral aciclovir 200mg 5 times daily for 5 days, with intravenous
      therapy reserved for complicated episodes. Although topical aciclovir may be of
      benefit, no improvement in the systemic symptoms is provided by this formulation.
      No preparation prevents the onset of recurrent episodes. The management of
      recurrent episodes is more controversial, with studies of episodic treatment with
      both topical and oral aciclovir yielding mixed and at times conflicting results.
      Episodic treatment with oral aciclovir initiated early by the patient appears to
      have the most favourable results, and if initiated at the onset of prodromal
      symptoms may abort the episode in some patients. In patients with frequent
      recurrences, suppressive therapy with oral aciclovir should be considered. A
      starting dose of 200mg 4 times daily appears to be the most effective, although
      400mg twice daily may suffice. The total daily dose should be reduced as far as
      possible, and treatment should be interrupted on a yearly basis to determine the
      need for continuing suppression. The management and pharmacological therapy of
      genital HSV in pregnancy remains controversial and studies of oral aciclovir in
      late pregnancy are currently under way. Genital HSV infection may be particularly
      severe in the immunocompromised host and suppressive oral aciclovir should be
      initiated promptly. HSV resistance to aciclovir is an increasing problem in such
      patients, in particular those infected with HIV, and may necessitate treatment
      with intravenous foscarnet.

PMID- 7512901
TI  - Changing from porcine to human insulin.
AB  - The development of hypoglycaemia unawareness is associated with long duration of
      diabetes, improved glycaemic control, alcohol intake and recurrent hypoglycaemia.
      However, current evidence suggests that neither frequency of severe episodes nor
      mortality from hypoglycaemia are increased following a change from animal to
      human insulin. Nevertheless, a small number of patients continue to report an
      alteration in the nature of hypoglycaemic warning symptoms following a change in
      insulin species. This is possibly a consequence of a reduced catecholamine
      response to lowering blood glucose levels or to species differences in the effect
      of insulin on central nervous system function. In practical terms, it seems
      sensible to warn patients that the nature of the symptoms associated with
      hypoglycaemia might alter following conversion from porcine to human insulin. At
      the time of the changeover, patients should be encouraged to perform frequent
      blood glucose measurements. Also, the usual insulin dose should be reduced by 10%
      at the start of human insulin treatment. Other aspects of insulin treatment
      including injection technique, meal timing, exercise, etc. should be discussed.
      For patients who are convinced that loss of warning of hypoglycaemia occurred
      after conversion from porcine to human insulin, a change back to animal insulin
      would be preferred to relaxing glycaemic control in the first instance. Pressure
      should be brought to bear on the pharmaceutical industry to maintain the
      availability of animal insulins for the small number of patients who have
      experienced problems with human insulin.

PMID- 7512900
TI  - Clinical pharmacology and modification of autoimmunity and inflammation in
      rheumatoid disease.
AB  - The increased understanding of the mechanisms which underlie rheumatoid disease
      has been accompanied by a more appropriate use of the limited repertoire of
      therapeutic agents. Conventional second-line drugs still have a role in everyday
      practice. The efficacy of these agents in reducing the severity of clinical signs
      of joint inflammation, whilst at the same time causing significant reductions in
      the laboratory measures of the acute phase response is undoubtedly confirmed by
      meta-analysis of several therapeutic trials of these agents. Whether or not these
      agents can influence outcome, usually assessed in terms of radiological
      progression, is more contentious. Furthermore, their toxicity in long term use is
      not inconsiderable. However, newer agents may play a more important part in
      therapy in the future. Such therapy can be designed to specifically interfere
      with the abnormalities of the immune system which characterise rheumatoid
      arthritis. Many of the agents reviewed have been successfully applied to animal
      models of arthritis but we still await large randomised controlled studies in
      humans to determine their clinical efficacy and toxicity. In view of the
      complexity of the immunological abnormalities in rheumatoid arthritis, it may be
      necessary to consider using a number of such agents in any particular patient.
      This should result in more rational therapy in rheumatoid arthritis.

PMID- 7512907
TI  - Quantitative EEG analysis in early onset Alzheimer's disease: correlations with
      severity, clinical characteristics, visual EEG and CCT.
AB  - We report EEG findings in 15 presenile Alzheimer patients (probable Alzheimer's
      disease according to NINCDS-ADRDA criteria) in relation to clinical
      characteristics. The quantitative EEG was analysed in terms of absolute band
      power while accounting for EOG and EMG artifacts, respectively. The degree of
      dementia is strongly reflected by an increase of power in the delta frequency
      band, accentuated on the left hemisphere, as well as decrease of alpha activity.
      Longer duration of disease is associated with a decrease of power in the alpha
      frequency band, earlier age at onset with an additional increase of power in the
      theta frequency band. Visual EEG evaluation correlates highly with the degree of
      dementia, in contrast to visually assessed CCT.

PMID- 7512905
TI  - Valproic acid. A reappraisal of its pharmacological properties and clinical
      efficacy in epilepsy.
AB  - Valproic acid is a branched-chained fatty acid, structurally unrelated to any
      other antiepileptic drug. Since publication of the original review in the Journal
      in 1977, several clinical trials have documented its efficacy and safety in
      adults and children for the treatment of generalised seizures (absence, tonic
      clonic, myoclonic), partial seizures (simple, complex, secondarily generalised)
      and compound/combination seizures (including those refractory to treatment with
      other antiepileptic drugs). Valproic acid monotherapy has demonstrated efficacy
      equivalent to that of carbamazepine, phenytoin, and phenobarbital in the
      treatment of both generalised and partial seizures and ethosuximide in the
      treatment of absence seizures. Adverse effects associated with the drug are
      primarily gastrointestinal (nausea, vomiting, dyspepsia) in nature, although the
      use of enteric-coated formulations has reduced the incidence of abdominal
      discomfort. Weight gain, tremor and transient hair loss are commonly reported.
      Importantly, valproic acid has minimal neurological adverse effects (sedation,
      ataxia, impairment of cognitive function) compared with other antiepileptic
      drugs, a finding that may be of particular relevance in many patients with
      epilepsy. The incidence of rare, fatal liver failure has been greatly reduced by
      identifying and avoiding administration of valproic acid to high risk patient
      populations. An estimated risk of 1 to 2% for neural tube defects, predominantly
      spina bifida aperta, with maternal use of valproic acid therapy has been
      reported. Valproic acid inhibits hepatic drug metabolism and displaces other
      highly bound drugs from their plasma protein binding sites. Therefore,
      coadministered drugs which are highly protein bound or hepatically metabolised
      may require dosage adjustment. Enzyme-inducing antiepileptic drugs may increase
      valproic acid metabolism and necessitate increasing its dosage. Thus, comparative
      trials and extensive clinical experience have demonstrated the efficacy and
      tolerability of valproic acid and support its role as a valuable and well
      established first-line treatment for patients with a broad range of seizure
      types.

PMID- 7512908
TI  - Intracerebral recording of movement related readiness potentials: an exploration
      in epileptic patients.
AB  - Readiness potentials (RPs) preceding voluntary self-paced limb movements were
      recorded intracerebrally in 13 patients suffering drug resistant, intractable
      epilepsy. Multilead depth electrodes were positioned using the Talairach's
      coordinate system; they allowed simultaneous recording from the external and
      mesial cortices and from the interposed white matter during self-paced unilateral
      hand or plantar flexions. Our intracerebral explorations have shown RPs in the
      primary motor cortex (MC) contralateral to the movement and in both supplementary
      motor areas (SMAs), indicating that at least 3 cortical sites become active
      before the movement. At variance with the scalp RPs recorded in the same
      patients, the intracerebral potentials were either negative, or positive,
      depending on the recording site. No consistent differences in duration and time
      of onset could be established between the MC and the SMA RPs, at least with the
      used time resolution. RPs were only occasionally observed in the parietal cortex
      and hippocampus and none were recorded from the amygdala, the temporal, temporo
      occipital, prefrontal, frontal and cingular cortices. The wide topographical
      distribution of the scalp RPs may not be fully explained by the above
      intracortical findings, leaving the possibility that other generators exist,
      whose locations remain to be determined.

PMID- 7512909
TI  - Stereo-EEG of interictal and ictal electrical activity of a histologically proved
      heterotopic gray matter associated with partial epilepsy.
AB  - Magnetic resonance imaging allows the identification of heterotopic gray matter
      (HGM) in medically intractable partial epilepsies. The relationships between HGM
      and the epileptogenic zone remain, however, unclear. In a case of a temporo
      parietal epilepsy studied by stereo-EEG, interictal and ictal electrical activity
      of a temporal HGM were recorded, showing: (1) an intralesional electrical
      activity, (2) the possible presence of asynchronous spikes, and (3) an early but
      never initial, or isolated, involvement during ictal discharges. This suggests
      that the presurgical and surgical management of HGM must be guided, as for other
      lesions, by the coherence existing between ictal clinical and electrical
      features, and anatomical data.

PMID- 7512906
TI  - Berger lecture. Is Berger's dream coming true?
AB  - In the last quarter of our century technologies have been developed that permit
      us to measure and localize with previously unknown precision physiological
      concomitants of mental activities. Human in vivo cerebral psychophysiology has
      come of age, decades after the discovery of EEG. In part this has come about
      through the development of PET and most recently dynamic MRI. However, it is
      hardly known today that the concepts which underlie these modern methods of
      studying the physiological correlates of human mental activity were the focus of
      Berger's early research at the onset of his scientific career at the turn of the
      century. Indeed at that time he attempted to study human mental function through
      measuring cerebral blood flow by means of plethysmography applied to patients who
      had pulsating skull defects. He also measured intracerebral temperature changes
      during neurosurgical procedures in awake, locally anesthetized, patients in a
      quest of identifying metabolic concomitants of mental activity. He was thus well
      ahead of his time, but was forced to give up these methods because they were not
      commensurate to the task. Only at age 50 he turned to electrophysiology and
      discovered the EEG. At last he was able to identify some electrophysiological
      facets of human psychophysiology related to attention, sleep, wakefulness and
      coma. This essay will illustrate some examples of PET, functional MRI,
      computerized EEG and cerebral electrical stimulation studies that show that
      Berger's conceptual approaches to human psychophysiology, even though he could
      not effectively apply them himself, were correct and have become powerful tools
      of modern neuroscience.

PMID- 7512910
TI  - Extended sleep in humans in 14 hour nights (LD 10:14): relationship between REM
      density and spontaneous awakening.
AB  - The sleep patterns of 8 normal subjects living in a winter-type photoperiod (10 h
      light and 14 h darkness; LD 10:14) for 4 weeks were characterized by the presence
      of periods of spontaneous wakefulness alternating with periods of spontaneous
      sleep. Transitions from sleep to wakefulness occurred much more frequently out of
      REM sleep than out of NREM sleep (P < 0.002). REM periods that terminated in
      wakefulness showed shorter REM durations (P < 0.0005) and higher REM densities (P
      < 0.0005) than REM periods that did not terminate in wakefulness. The authors
      discuss these results in terms of a possible relationship between REM density and
      arousal level. The higher REM density preceding wakefulness and the increased
      number of REM periods terminating in spontaneous awakenings could reflect an
      enhanced level of a brain arousing process, resulting from reduced sleep pressure
      in the extended nights.

PMID- 7512903
TI  - Antacids. Indications and limitations.
AB  - Antacids have served us well for over a century. In terms of peptic ulcer
      disease, the attitude in the late 1950s to 1970s that antacids should be taken
      only on demand was unjustified and erroneous. 13 recent endoscopic controlled
      studies have confirmed the efficacy of antacids in the healing of duodenal ulcer,
      achieving about 75% healing in 4 weeks. The efficacy of antacids in promoting
      gastric ulcer healing has been less well studied and the results are
      controversial. The most appropriate and economical antacid regimens for the
      treatment of duodenal ulcer disease should include tablets or liquid that have
      acid neutralising capacity of 400 mmol/day given at least an hour after meals. As
      a long term therapy, antacids appear to work, but need be taken in multiple daily
      doses, a regimen which is unlikely to meet with long term patient compliance.
      Patients with gastro-oesophageal reflux disorders or pregnancy-related reflux
      have also benefited from the usage of antacids ad libitum. Early previous studies
      have clearly demonstrated the efficacy of antacids in reducing gastro-oesophageal
      reflux and healing of reflux oesophagitis. The acidity of the gastric contents is
      the major determining factor in the outcome of the aspiration pneumonitis
      occurring during delivery. The prophylactic use of antacids during delivery has
      helped to reduce the severity of this complication. Similarly, the prophylactic
      administration of antacid aiming to maintain gastric pH between 3.5 to 7.0 has
      resulted in significant reduction of bleeding due to stress associated ulcers
      and/or erosive haemorrhagic gastritis in critically ill patients. Antacid
      therapy, however, is controversial in the management of nonulcer dyspepsia or
      nonsteroidal anti-inflammatory drug related upper gastrointestinal mucosal
      damage. Undoubtedly, antacids have major roles to play in the treatment of
      gastric acid related disorders. They have clear advantages and disadvantages when
      compared with the antisecretory agents. New proton pump inhibitors in particular
      have certainly superseded antacids and even the H2-receptor antagonists in many
      respects. However, the long term safety record of antacids remains unsurpassed by
      any of the new antisecretory agents.

PMID- 7512911
TI  - Reptilian waking EEG: slow waves, spindles and evoked potentials.
AB  - Signal spectral analysis procedures were used to compute the power spectrum of
      Gallotia galloti lizards EEG at different (5-35 degrees C) body temperatures. EEG
      power spectra were mainly characterized by a low frequency peak between 0.5 and 4
      Hz which was present at the different body temperatures. A second spectral peak,
      corresponding to spindles of similar pattern to the sleep spindles of mammals,
      also appears in the spectra. The peak frequency of the spindles increased with
      the body temperature. Flash evoked potentials were characterized by a slow
      triphasic component upon which a spindle was superimposed, adopting a morphology
      similar to the K complexes of mammalian sleep. The characteristics of this EEG
      and evoked potentials support the hypothesis of homology between the waking state
      of the reptiles and the slow wave sleep of mammals.

PMID- 7512912
TI  - Central and peripheral nervous system conduction in mitochondrial myopathy with
      chronic progressive external ophthalmoplegia.
AB  - Involvement of the peripheral and central nervous systems in mitochondrial
      myopathy with chronic progressive external ophthalmoplegia (CPEO) has been
      demonstrated clinically and electrophysiologically. Systematic
      electrophysiological investigations of the peripheral and central nervous
      systems, particularly of cortico-spinal tract function, however, are not
      available. We studied peripheral and central nervous system involvement in 28
      patients with histologically and biochemically proven mitochondrial CPEO by motor
      and sensory nerve conduction tests, by somatosensory, auditory and visual evoked
      potentials and, for the first time, by transcranial magnetic stimulation. Nervous
      system involvement could be demonstrated in 24 patients, affecting the peripheral
      and central nervous systems in 18 and 10 patients, respectively. Evidence of
      cortico-spinal tract involvement was found in 4 patients, which was clinically
      expected in only 2. Therefore, dysfunction of the cortico-spinal tract in
      mitochondrial CPEO may occur more frequently than so far assumed. Generally,
      electrophysiological tests serve as valuable supplements to clinical examination
      in patients with mitochondrial CPEO and may be especially helpful in therapeutic
      studies, i.e., coenzyme Q administration.

PMID- 7512904
TI  - Inhaled fluticasone propionate. A review of its pharmacodynamic and
      pharmacokinetic properties, and therapeutic use in asthma.
AB  - Fluticasone propionate is an androstane carbothioate glucocorticosteroid with
      almost twice the topical anti-inflammatory potency of beclomethasone
      dipropionate. Importantly, it is not appreciably absorbed from the
      gastrointestinal tract. However, the fraction of active drug absorbed from the
      lungs after inhalation, and therefore total systemic availability, has yet to be
      determined. Inhaled fluticasone propionate administered at dosages of 1500
      micrograms/day for 1 year or 2000 micrograms/day for 6 weeks did not cause
      clinically significant pituitary-adrenal suppression. Preliminary data from 2
      published trials also indicate no significant effect on growth in children.
      However, wider clinical experience is needed to clarify the effects of long term
      administration on pituitary-adrenal function, bone metabolism and attainment of
      adult height in children. In clinical studies, inhaled fluticasone propionate was
      at least as effective as beclomethasone dipropionate or budesonide when
      administered at half the dosage of the comparators in patients with mild to
      moderate or severe asthma. Limited data suggest that fluticasone propionate also
      has considerable potential in the management of childhood asthma. In trials of up
      to 1 year in duration, fluticasone propionate appeared to be well tolerated by
      both adults and children. Whether an improved tolerability profile compared with
      other corticosteroids is a major clinical benefit of the extremely low oral
      bioavailability of inhaled fluticasone propionate requires confirmation.
      Nevertheless, on the basis of available data from initial clinical trials of
      mostly limited duration, inhaled fluticasone propionate offers an effective
      treatment option for the management of asthma, with the potential of an enhanced
      safety profile.

PMID- 7512914
TI  - Dipole source localization in a case of epilepsia partialis continua without
      premyoclonic EEG spikes.
AB  - A 72-year-old woman with epilepsia partialis continua (EPC) of the right foot is
      presented. Rhythmic myoclonic jerks were localized to the 1st and 2nd toes of the
      right foot and persisted for 72 h. EEG/video monitoring did not show any
      epileptiform transient in association with myoclonic jerks. MRI and MRA
      demonstrated an arterio-venous malformation involving the left fronto-parietal
      parasagittal area. Using the EMG signal from the myoclonic jerk we back-averaged
      the EEG 640 msec before and after the onset of the twitch. A negative-positive
      deflection was observed preceding the myoclonic jerks by 128-188 msec. Voltage
      topographic mapping showed a negative maximum in the left centro-parietal region.
      A multiple spatio-temporal dipole model was applied to the back-averaged
      deflection preceding the myoclonus. The patient's MRI was used to determine the
      center of the best fitting sphere, and the model was corrected accordingly. The
      best dipole solution consisted of 3 dipoles localized in the parasagittal frontal
      cortex, in the location of the motor representation for the foot. The utilization
      of a combined technique of back-averaging from the myoclonus and dipole source
      localization supported the epileptogenic etiology in this case.

PMID- 7512915
TI  - Assessment of human motor unit twitches--a comparison of spike-triggered
      averaging and intramuscular microstimulation.
AB  - We recorded twitches of single motor units (MUs) in the human first dorsal
      interosseus muscle using either spike-triggered averaging (STA; 236 MUs in 12
      normal subjects) or low-rate intramuscular microstimulation of motor axons (IMS;
      200 MUs in 20 normal subjects). We analysed twitch force (TF), maximal rate of
      rise of force (MRRF), contraction time (CT) and half-relaxation time (HRT). MRRF,
      CT and HRT were significantly smaller with STA than with IMS whereas TFs were
      fairly similar. Higher stimulus rates (up to 14 Hz) in IMS resembling the
      voluntary MU firing rates in STA were associated with a decrease of all twitch
      parameters because of partial fusion of the twitches (20 MUs). Concerning MRRF,
      CT and HRT, the reduced values matched those obtained by STA, suggesting that the
      underestimation of these parameters in STA can be mainly attributed to partial
      fusion. The reduction of TF with high rate IMS but not with STA reveals that
      other factors such as MU synchronization and non-linear force summation of MU
      contractions must counteract the effects of partial fusion in STA. We conclude
      that both STA and IMS are appropriate for assessing TFs in man while the time
      dependent parameters MRRF, CT and HRT will be underestimated with STA.

PMID- 7512916
TI  - Agonist and antagonist EMG activation during isometric torque development at the
      elbow in spastic hemiparesis.
AB  - Voluntary isometric step contractions of the elbow flexor and extensor muscles
      were studied in a group of patients with paresis arising as the result of
      unilateral cerebral lesion and in a control group of normal subjects. For each
      subject the maximum isometric torque in flexion and extension was obtained, along
      with a series of graduated torque steps up to this maximum, in order to perform a
      regression analysis between torque developed and the associated agonist and
      antagonist EMG. This relationship proved to be linear in all normal subjects and
      in all but the most paretic spastic patients. If the patients were grouped
      according to their ability to make discrete large angle flexion and extension
      movements at the elbow, a clear correspondence was seen between increasing
      movement disability and the degree of paresis. No significant differences were
      found in the torque/EMG relationship of spastic patients when either elbow
      extensors or flexors were acting as the agonist in a contraction. Similarly, no
      evidence of exaggerated antagonist co-activation was found. It is concluded that,
      in the upper arm muscles, hemiparesis following stroke cannot, under isometric
      conditions, be attributed to hyperactivity of antagonist muscles.

PMID- 7512913
TI  - Should sleep EEG record always be performed after sleep deprivation?
AB  - Sleep deprivation (SD) is a known activator of epileptiform EEG activity in
      patients with epilepsy. In the workup of these patients, EEG recordings are
      performed following SD both in the awake state and during sleep. The latter
      significantly increases the duration and the cost of the examination; the
      specific yield of sleep tracing in single-session wake-sleep record after SD has
      not been evaluated in adult patients. Our study tried to answer this question,
      analyzing consecutive recordings of 76 adult patients who had an epileptiform
      abnormality in the SD record. Thirty-five of the patients were treated with
      antiepileptic drugs at the time of the study. After SD of 24-26 h, 1000-1500 mg
      of chloral hydrate were administered; an 18-channel standard awake EEG was
      performed, followed by 30 min sleep recording. Epileptiform activity was recorded
      in the wake part only in 7 (9%, 3 focal, 4 generalized); in 39 (51%) the activity
      was seen in both awake and sleep parts (21 focal, 5 focal with secondary
      generalization and 13 generalized); and in 30 (40%) it was found in the sleep
      part only (23 focal, 1 focal with secondary generalization and 6 generalized).
      Whenever epileptiform activity was apparent in both parts of the recording, its
      configuration and localization were identical in the sleep and the wake EEGs.
      This phenomenon was observed in both treated and untreated patients. In combined
      wake-sleep recording following SD in adults, sleep tracing may reveal
      epileptiform activity not demonstrated during the preceding wake EEG. However, if
      epileptiform activity appears already in the wake recording, subsequent sleep
      tracing may be redundant.

PMID- 7512917
TI  - Magnetic transcranial and electrical stylomastoidal stimulation of the facial
      motor pathways in Bell's palsy: time course and relevance of electrophysiological
      parameters.
AB  - Facial nerve motor neurography was performed at various times after the onset of
      Bell's palsy in 97 patients. Stimulation of the facial nerve was performed (1)
      electrically in the fossa stylomastoidea (ElStim), and (2) magnetically in the
      labryinthine segment of the facial canal (MagStim), evaluating different coil
      positions over the skull. Additionally, the face-associated motor cortex was
      stimulated magnetically in 47 patients (CxStim). A marked reduction of the
      amplitudes of the compound muscle action potentials (CMAP) evoked by MagStim on
      either m. nasalis or mentalis, or both, was observed which was clearly more
      pronounced than the amplitude reduction to ElStim. This discrepancy occurred very
      early during the disease, the mean amplitude (expressed in percent of the
      amplitude on the unaffected side) being 82% (S.D. 9.1) for ElStim and 1% (2.7)
      for MagStim at days 0-4. It persisted for several months, often when facial nerve
      function had recovered to normal, as assessed by clinical observation, ElStim,
      and CxStim. This amplitude decrease to MagStim, which appears to be related to a
      locally enhanced stimulation threshold of the facial nerve, is a very sensitive
      and reproducible finding in Bell's palsy. It may prove specific of the disorder,
      of diagnostic value, and of interest in the follow-up of patients during
      treatment trials.

PMID- 7512918
TI  - Origin of the facial long latency responses elicited by magnetic stimulation.
AB  - With magnetic stimulation (MS) it is possible to elicit bilateral long latency
      facial motor responses (LLRs). Due to a relatively wide magnetic field, the site
      of neural activation may take place in many different structures. The purpose of
      this study was to determine the site of origin of facial LLRs. The motor long
      latency responses were recorded bilaterally on the naso-labial folds (NLFs) with
      reference electrodes on the nose, and on some subjects also with reference
      electrodes on the chin. The stimulating coil was placed in the right parietal
      area. LLRs obtained with MS were compared to LLRs elicited electrically at the
      right stylomastoid foramen, supraorbital foramen, as well as cutaneous sensory
      area V1 of the trigeminal nerve. In addition, right sided high intensity
      electrical stimuli, paired magnetic stimulation and electrical stimulation with
      interstimulus intervals ranging from 0 to 80 msec were also applied for
      comparison. LLRs recorded with reference to the nose were always elicitable with
      MS as well as with the other stimulation procedures. The responses elicited with
      MS did not differ from those elicited electrically at various extracranial
      stimulation sites. With paired stimuli the second LLRs were inhibited by the
      preceding stimulation, whether given magnetically or electrically. In subjects
      with elicitable LLRs with chin references, the responses were always bilateral.
      Based on the similar characteristics with extracranial electrical stimuli,
      bilateral distribution of the responses, and inhibition of the second response
      with paired stimuli, it is concluded that the neural origin of LLRs to MS is in
      the extracranial trigeminal or facial nerve branches.

PMID- 7512919
TI  - Reliability of transcranial magnetic stimulation for mapping the human motor
      cortex.
AB  - Motor mapping using transcranial magnetic stimulation has been applied to the
      study of adaptive and restorative mechanisms of the motor cortex. To date, the
      reproducibility of mapping techniques has yet to be investigated in detail and/or
      confirmed. We report a technique used to map the abductor pollicis brevis (APB)
      and abductor digiti minimi (ADM) motor cortices of 6 normal volunteers, each
      studied on 2 occasions separated by several weeks (range of 21-132 days). APB and
      ADM results were analyzed separately, with area and volume characteristics
      subjected to analysis of variance. Coefficients of variation, which should be
      low, ranged from 14% to 37% and coefficients of reliability, which should be
      high, ranged from 63% to 94%, indicating that the described technique for motor
      mapping is responsible.

PMID- 7512899
TI  - Anthracycline antibiotics in cancer therapy. Focus on drug resistance.
AB  - 30 years ago an anthracycline antibiotic was shown to have antineoplastic
      activity. This led to the development of well over 1000 analogues with a vast
      spectrum of biochemical characteristics. Many biological actions have been
      described. The original anthracyclines are active against many types of cancer
      and are an integral part of several curative combinations. They are ineffective
      against other tumours. Although some analogues show an altered spectrum of
      activity or an improved therapeutic index relative to the older agents, it is not
      clear that cardiotoxicity can be totally avoided with these agents. Primary and
      secondary resistance to anthracyclines remain major clinical problems.
      Pharmacokinetic studies have been of limited help in explaining this.
      Overexpression of a surface-membrane permeability glycoprotein (Pgp) was
      identified in ovarian cancer of patients who had clinical multidrug resistance in
      1985. This led the way for the discovery of a number of resistance mechanisms in
      vitro. Some of these have been found in more than 1 type of cell line, and more
      than 1 mechanism may exist in a single cell. Additional resistance proteins have
      been identified, qualitative and quantitative alterations of topoisomerase II
      have been described, and some mechanisms in other systems have not yet been
      identified. Some of these may prove to be important in clinical drug resistance.
      Drugs such as calcium antagonists and cyclosporin, studied initially for their
      ability to block the Pgp pump, appear to be heterogeneous in this capacity and
      may have additional sites of action. It will be critical for clinical studies to
      define the precise resistance mechanism(s) that must be reversed. To date this
      has been difficult, even in trials ostensibly dealing with the original Pgp.
      Liposomes can potentially alter toxicity and target drug delivery to specific
      sites. In addition, they may permit the use of lipophilic drugs that would
      otherwise be difficult to administer systemically. Resistant tumours may be
      sensitive to anthracyclines delivered by liposomes. To reduce cardiac toxicity,
      administering doxorubicin (adriamycin) by slow infusion through a central-venous
      line should be considered whenever feasible. Monitoring of cardiac ejection
      fraction and the use of endomyocardial biopsy will permit patients to be treated
      safely after they reach the dose threshold at which heart failure begins to be a
      potential risk. A number of structurally modified anthracyclines with the
      potential advantages of decreased cardiotoxicity and avoidance of multidrug
      resistance mechanisms are entering clinical trials. Meanwhile, the vast weight of
      clinical experience leaves doxorubicin as a well tolerated and effective choice
      for most potentially anthracycline-sensitive tumours.

PMID- 7512921
TI  - The time constants of motor and sensory peripheral nerve fibers measured with the
      method of latent addition.
AB  - The time constants of motor and sensory fibers in the human ulnar, median and
      tibial nerves were determined using the method of latent addition. Two square
      wave stimuli were applied: the first one was subthreshold and the second, at
      various delays relative to the first, was adjusted to achieve threshold
      activation. Strength-delay curves were obtained, from which the time constant was
      determined using a mathematical model. Sensory fibers had time constants that
      were about 3 times the time constant for motor fibers. The strength-delay curves
      gave similar time constants as those obtained from strength-duration curves.

PMID- 7512920
TI  - The effect of magnetic coil orientation on the latency of surface EMG and single
      motor unit responses in the first dorsal interosseous muscle.
AB  - We examined the effect of the orientation of a figure-of-eight coil on the
      latency of surface electromyographic (EMG) responses and the firing pattern of
      single motor units evoked in the first dorsal interosseous muscle by transcranial
      magnetic brain stimulation. Two coil positions were used: the coil held on a
      parasagittal line either with the induced current in the brain flowing in a
      postero-anterior direction (PA) or with the current flowing latero-medially (LM).
      The results were compared with those observed after anodal electrical
      stimulation. LM stimulation produced surface and single unit responses which
      occurred 0-3 msec earlier than PA stimulation. In many cases responses to LM
      stimulation had the same latency as those produced by anodal electrical
      stimulation. Responses evoked by LM stimulation were less affected by changes in
      motor cortical excitability (cortico-cortical inhibition and transcallosal
      inhibition) than those to PA stimulation. We suggest that LM stimulation can
      sometimes stimulate corticospinal fibres directly, at or near the same site as
      anodal stimulation. In contrast, PA stimulation tends to activate corticospinal
      fibres trans-synaptically. The difference in stimulation sites may make a
      comparison of PA and LM stimulation a useful method of localising changes in
      corticospinal excitability to a cortical level.

PMID- 7512923
TI  - Medial (cutaneous) branch of deep common peroneal nerve: recording technique and
      a case report.
AB  - An isolated lesion of the medial branch of the deep common peroneal nerve is rare
      and so far there do not appear to have been any reports of a recording method or
      normative data for this sensory action potential (SAP). Just such a case is
      described along with an appropriate recording technique. Control data were
      subsequently obtained from 50 normal volunteers.

PMID- 7512922
TI  - Differences in the handling of the EMG examination at seven European
      laboratories.
AB  - This study was undertaken to analyse epidemiological and methodological
      differences in referral pattern, examination techniques and distribution of
      diagnoses among different European EMG laboratories. Seven European EMG
      laboratories filled in questionnaires and sampled 700 cases retrospectively. The
      use of needle or surface electrodes for nerve studies and the selection of
      quantitative techniques for muscle studies exhibited considerable variation. The
      pattern of referral varied with respect to the type of referral source and the
      neurological expertise of the referring physician. The proportion of patients
      without any neurophysiological abnormality ranged from 16 to 33%. The 3 most
      common diagnostic groups were mononeuropathies, polyneuropathies and
      radiculopathies although a great inter-laboratory variation was found. The
      proportion of patients with multiple diagnoses varied from 0 to 23% and most of
      these diagnoses were from a few known combinations. The presence of an inter
      laboratory variation suggests that the quality of the EMG examination may be
      improved by focussing on the use of techniques, strategies and diagnostic
      criteria.

PMID- 7512924
TI  - Intramuscular potential changes caused by the presence of the recording EMG
      needle electrode.
AB  - A comprehensive volume conductor study of single fiber needle EMG (SF EMG) has
      been made. The electrode shaft is described as a passive inhomogeneity in the
      volume conductor. The most important observation is a substantial increase in
      single fiber action potential (SFAP) amplitude (up to 70%) for muscle fibers
      observed from a short distance. For SFAPs from muscle fibers located on the back
      of the SF electrode a shadow effect occurs which can result in a maximal
      amplitude decrease of 50%. SFAP wave form changes were observed only in
      situations without practical consequences or beyond physical reality. The
      presence of the needle shaft causes an anisotropy-like behavior of the relation
      between leading-off point to muscle fiber distance. The observed amplification
      due to the presence of the needle cannula decreases faster in the direction
      parallel to the cannula than in the direction normal to it: due to the
      amplification of SFAPs from muscle fibers observed from a short distance, the
      maximal distance from which SFAPs are included in fiber density measurements
      (amplitude greater than 0.2 mV) is raised from 380 microns to 460 microns. Also,
      the consequences of the formation of an edematous layer around the needle cannula
      have been studied. It was shown that the effect of high conductive fluid around
      the needle electrode can counteract the effects caused by the presence of the
      electrical double layer.

PMID- 7512925
TI  - The effects of skinfold thickness on the selectivity of surface EMG.
AB  - We investigated the effects of skinfold thickness and electrode orientation on
      the ability to record selectively from a localized region of a muscle using
      arrays of surface electrodes. EMG activity elicited by electrical stimulation and
      by voluntary contraction of the biceps muscle was recorded from subjects with
      skinfold thicknesses ranging from 2 mm to 21 mm. The selectivity of the surface
      electrodes increased as the skinfold thickness decreased; action potentials were
      more rapidly attenuated and underwent less low-pass filtering. As a result, the
      EMG recorded during a voluntary contraction at one site became less highly
      correlated with that recorded at neighboring sites as skinfold thickness
      decreased. We were able to determine the axis of action potential propagation
      (muscle fiber direction) through comparison of the amplitude and delay of cross
      correlation peaks from pairs of colinear electrodes oriented at angles to one
      another, although the thicker the skinfold the lower the resolution. It was clear
      that the ability to localize EMG signal sources deteriorated as the amount of
      subcutaneous fat between the surface recording site and the active muscle fibers
      increased.

PMID- 7512926
TI  - Involvement of central serotonergic pathways in analgesia elicited by salmon
      calcitonin in the mouse.
AB  - The contribution of central serotonergic pathways to the analgesic activity
      induced by salmon calcitonin in the writhing test was investigated. Salmon
      calcitonin was administered to mice after lesioning of the ascending and
      descending serotonergic pathways by means of i.p. administration of p
      chloroamphetamine (40 mg/kg, for 2 days) or p-chlorophenylalanine (300 mg/kg, for
      3 days). The analgesic effect induced by salmon calcitonin at the doses of 10 and
      20 IU/kg was not evident in mice previously treated with p-chloroamphetamine or p
      chlorophenylalanine. However, the analgesic effect of salmon calcitonin 40 IU/kg
      was not significantly modified by p-chloroamphetamine or p-chlorophenylalanine
      pretreatment. Salmon calcitonin did not alter the depletion of 5
      hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid after p-chloroamphetamine
      or p-chlorophenylalanine administration. Similarly, this hormone did not change
      the NSD 1015-induced accumulation of 5-hydroxytryptophan or the tranylcypromine
      induced accumulation of 5-HT. These results indicate that although salmon
      calcitonin does not influence the synthesis and metabolism of 5-HT, it does
      require the integrity of the serotonergic system in order to cause analgesia.

PMID- 7512928
TI  - Identification of alpha 2-adrenoceptors in rat lymph nodes and spleen: an
      autoradiographic study.
AB  - The anatomical localization and pharmacological characteristics of alpha 2
      adrenoceptors were studied in rat lymphoid tissues by quantitative
      autoradiography with [3H]bromoxidine as a ligand. In lymph nodes, a significant
      density of these receptors was found in the capsule, interfollicular cortex and
      medullary cords, while only very low densities were observed in the paracortex
      and germinal centres. In the spleen, these receptors appeared to be mainly
      distributed in the marginal zone of white pulp as well as in the red pulp. These
      results suggest a role for alpha 2-adrenoceptors in the interaction between
      nervous and immune systems.

PMID- 7512927
TI  - Hippocampal noradrenaline release is modulated by gamma- and delta
      hexachlorocyclohexane isomers: which mechanisms are involved?
AB  - The differential effects of gamma- and delta-hexachlorocyclohexane isomers on 25
      mM K(+)-evoked release of [3H]noradrenaline were studied in hippocampal slices
      treated with selected agents to activate or block L- and N-type Ca2+ and Na+
      voltage-sensitive ion channels, Cl- transport and Ca(2+)-dependent protein
      activity. At maximally effective concentrations, the L- and N-type Ca2+ channel
      blockers nifedipine and omega-conotoxin, respectively, and the Na+ channel
      antagonist tetrodotoxin did not modify the enhancement of K(+)-evoked
      [3H]noradrenaline release induced by gamma-hexachlorocyclohexane. Likewise, under
      activation of protein kinase C by phorbol 12,13-dibutyrate (PDB) or inhibition of
      calmodulin by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), the
      stimulatory effect of gamma-hexachlorocyclohexane remained almost unchanged. The
      Cl- transport blocker 4,4-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS)
      significantly reduced the effect of gamma-hexachlorocyclohexane on
      [3H]noradrenaline release. The enhanced release in the presence of Bay K 8644,
      the L-type Ca2+ channel activator, was significantly inhibited by nifedipine but
      not by delta-hexachlorocyclohexane. The combination of omega-conotoxin and
      tetrodotoxin with delta-hexachlorocyclohexane did not alter the [3H]noradrenaline
      release effects of each agent alone. Activation of protein kinase C in the
      presence of delta-hexachlorocyclohexane resulted in a reduction of the delta
      isomer effect and in a potentiation of the PDB effect. W-7 did not further
      facilitate the inhibition induced by delta-hexachlorocyclohexane alone. These
      data suggest that hexachlorocyclohexane isomers may modify K(+)-evoked
      [3H]noradrenaline release by interacting with presynaptic molecular processes
      involving changes in Cl- membrane permeability and intracellular Ca2+
      homeostasis.

PMID- 7512929
TI  - Plasmodium falciparum: further characterization of a functionally active region
      of the merozoite invasion ligand EBA-175.
AB  - A 42 amino acid peptide, Pf EBA-175 (1062-1103), also called EBA-peptide 4 of the
      175-kDa Plasmodium falciparum sialic acid binding protein, a putative merozoite
      invasion ligand, has been shown to be a target of parasite growth inhibitory
      antibodies. We expressed and purified a recombinant protein, NS1-Pf EBA-175 (946
      1133) which included the 42 amino acid peptide, and compared antibodies induced
      by immunization with the protein to antibodies raised against the 42 amino acid
      peptide. Sera from rabbits immunized with the recombinant protein and the
      synthetic peptide immunoprecipitated authentic EBA-175, and had comparable ELISA
      titers against peptide Pf EBA-175 (1062-1103). However, IFAT titers against
      infected erythrocytes and growth inhibitory activity were substantially higher in
      sera from animals immunized with the 42 amino acid synthetic peptide. Epitope
      mapping of the 42 amino acid peptide identified a 19 amino acid peptide, Pf EBA
      175 (1069-1087), which blocked the ability of antibodies against the 42 amino
      acid peptide to (1) immunoprecipitate EBA-175, (2) bind to the 42 amino acid
      peptide in an ELISA, and (3) recognize infected parasites in an IFAT. Sera from
      rabbits immunized with the 19 amino acid peptide conjugated to KLH had excellent
      parasite growth inhibitory activity (at 1:5 serum dilution, 49.9 +/- 7.4%, mean
      +/- SD of three separate assays), but the activity was lower in each of the three
      assays than that of sera from rabbits immunized with the 42 amino acid peptide
      (67.8 +/- 24.8%). These data indicate that the activity of antibodies raised
      against the linear 42 amino acid peptide, Pf EBA-175 (1062-1103) are primarily,
      if not exclusively, directed against 19 of the 42 amino acids, and identify this
      region of Pf EBA 175 as a target for vaccine development.

PMID- 7512931
TI  - Clinical evaluation of a serological assay using a monoclonal antibody (TB72) to
      the 38 kDa antigen of Mycobacterium tuberculosis.
AB  - We examined an enzyme-linked immunosorbent assay (ELISA) modification of a
      radioimmunoassay, using the TB72 monoclonal antibody, as a serological test for
      tuberculosis in a clinical setting. Sera were obtained from 238 patients with
      suspected pulmonary tuberculosis, 30 patients treated for tuberculosis, 28
      contacts, and 480 random samples from inpatients. Antibody levels were measured
      as the dilution of serum causing 50% inhibition of binding of the TB72 monoclonal
      antibody, which binds to an epitope of the 38 kDa antigen specific to the
      Mycobacterium tuberculosis complex, a positive titre being > 3. Positive antibody
      titres were present in 21 out of 25 (84%) patients with smear-positive and 22 out
      of 27 (82%) patients with smear-negative, culture-positive tuberculosis, and 37
      out of 41 (90%) patients successfully treated for tuberculosis but without
      bacteriological confirmation of disease. Three out of 82 (4%) patients with a
      firm alternative diagnosis to tuberculosis gave a positive result. Serological
      tests were negative within 2.5 yrs of successful treatment. Patients without a
      definite diagnosis one year after tuberculosis had been suspected, and those who
      had received inadequate treatment for tuberculosis, were frequently positive (21
      out of 31 and 21 out of 32, respectively). Positive tests concurred with
      tuberculin reactivity in 8 out of 11 contacts given chemoprophylaxis. Screening
      of 480 random serum samples gave 22 positive titres, 16 of which were not
      associated with tuberculosis; none of these 16 had an antibody titre > 10. We
      conclude that the TB72 test provides additional information in the diagnosis and
      treatment of tuberculosis. Antibody titres > 10 suggests active tuberculosis;
      titres of 3-10 merit observation.

PMID- 7512930
TI  - Invertebrate host-parasite relationships: convergent evolution of a tropomyosin
      epitope between Schistosoma sp., Fasciola hepatica, and certain pulmonate snails.
AB  - Monoclonal antibodies (mAb) directed against Schistosoma mansoni tropomyosin
      isoform, SMTM (Xu et al. Experimental Parasitology 69, 373-392, 1989), were used
      to test for cross-reactivity with Biomphalaria glabrata antigens. One mAb (1F10)
      recognized antigens of 39, 41, and 80 kDa in a snail head/foot antigen
      preparation but not a hepatopancreas antigen preparation. Another mAb (1C1) cross
      reacted with a 39-kDa antigen in the head/foot extract but not in the
      hepatopancreas extract. Epitope mapping revealed the 1F10 epitope to be between
      amino acids 135 and 188 of both Bg39 (Dissous et al. Molecular and Biochemical
      Parasitology 43, 245-256, 1990) and BgTMII (Weston and Kemp, Experimental
      Parasitology 76, 358-370, 1993), while the 1C1 epitope was located between amino
      acids 189 and 213 of BgTMII. Various invertebrate species, including members from
      Trematoda, Pulmonata, Annelida, and Arthropoda, were tested for cross-reactivity
      with the monoclonal antibodies. While the 1F10 mAb displayed broad invertebrate
      cross-reactivity, the 1C1 mAb cross-reactivity was restricted to schistosomes, F.
      hepatica, and the pulmonate snails B. glabrata and Physa sp.

PMID- 7512932
TI  - The role of submucosal oedema in increased peripheral airway resistance by
      intravenous volume loading in dogs.
AB  - Pulmonary congestion leads to an increase in airway resistance. It is still
      unknown whether this is due to vascular engorgement or to submucosal oedema. The
      present study was designed to determine the relative contribution of these two
      potential mechanisms. We examined the effect of intravenous volume loading on
      canine peripheral airway resistance (Rp). Bronchoscopes were wedged in
      contralateral sublobar segments and used to record Rp during rapid infusion of
      normal saline. Volume loading with normal saline increased pulmonary capillary
      wedge pressure (PCWP) and Rp. Unlike normal saline, dextran 70 did not increase
      Rp when infused at a rate that produced similar changes in PCWP. During infusion
      of normal saline, delta Rp was significantly enhanced in lung segments previously
      challenged with dry air when compared to contralateral control lungs, unexposed
      to dry air, and the use of dextran 70 significantly reduced this effect.
      Vasoconstriction with phenylephrine significantly decreased baseline Rp, but did
      not completely reverse the effect of fluid infusion. In addition, in lung
      segments exposed to dry air, delta Rp was significantly greater after volume
      loading and treatment with phenylephrine when compared to contralateral control
      lung. Finally, muscarinic receptor blockade was ineffective in preventing Rp from
      increasing during infusion of normal saline. Our results suggest that volume
      loading-induced increases in Rp are not caused by either vascular engorgement or
      the stimulation of muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512933
TI  - Translocation of an SH2-containing protein tyrosine phosphatase (SH-PTP1) to the
      cytoskeleton of thrombin-activated platelets.
AB  - A significant protein tyrosine phosphatase (PTP) activity was found to be
      associated with the cytoskeleton of thrombin-stimulated platelets. Translocation
      of the enzyme became maximal within 1-2 min of thrombin stimulation and was
      suppressed by cytochalasin D or upon inhibition of aggregation. Immunoblotting as
      well as immunoprecipitation revealed that a PTP with two SH2 domains (SH-PTP1)
      displayed the same behaviour, translocation to the cytoskeleton showing the same
      time course as that observed for pp60c-src. We conclude that SH-PTP1 might
      represent a critical enzyme in the complex interplay between the various proteins
      regulating protein tyrosine phosphorylation in the cytoskeletal matrix.

PMID- 7512934
TI  - DNA damage by the glycation products of glyceraldehyde 3-phosphate and lysine.
AB  - In order to evaluate whether base modifications, apurinic/apyrimidinic site
      formation, strand breaks, or a combination of these lesions results from the
      interaction of glycation products with DNA, plasmid DNA was first reacted with
      these products, and then subjected to digestion with endonuclease III and
      endonuclease IV of Escherichia coli. Analysis of the differential effects of
      digestions with these enzymes by electrophoresis on agarose gels demonstrated
      that reactive glycation products produce both base modification and
      apurinic/apyrimidinic sites in DNA, in addition to the strand breaks observed
      after incubation with glycation products alone. These types of DNA damage may
      occur in specific diabetic cells where elevated levels of glycating sugars are
      associated with pathologic dysfunction.

PMID- 7512935
TI  - [Mean ratio of extrasystoles in patients with ischemic heart disease].

PMID- 7512936
TI  - Silicone-covered self-expanding metallic stents for the palliation of malignant
      esophageal obstruction and esophagorespiratory fistulas: experience in 32
      patients and a review of the literature.
AB  - Esophagogastric malignancies often are manifested with progressive dysphagia or
      esophagorespiratory fistulas. Palliative modalities currently available have
      significant limitations. A modified Gianturco-Rosch silicone-covered self
      expanding metallic Z stent was used in 32 consecutive patients with malignant
      esophageal obstruction (n = 24) or esophagorespiratory fistulas (n = 8). The
      stent was placed successfully in all patients. Dysphagia improved by at least two
      grades in 21 of the 24 patients (87.5%); the mean dysphagia grade fell from 3.21
      to 1.08. Six of the 8 patients with fistulas were able to resume a normal diet,
      and the other 2 were able to eat solids without symptoms of aspiration.
      Complications occurred in 10/32 patients (31%) and included stent migration (4
      patients), food impaction (2 patients), membrane disruption with tumor ingrowth
      (1 patient), tumor overgrowth (1 patient), early pressure necrosis with
      hemorrhage (1 patient), and late pressure necrosis with sepsis (1 patient). The
      latter 2 patients died, giving a mortality rate of 6.3%. Many complications were
      managed with endoscopic or interventional radiologic techniques. Although
      randomized prospective clinical trials are needed, the silicone-covered Gianturco
      Rosch Z stent offers promise for the effective palliation of malignant esophageal
      obstruction and esophagorespiratory fistulas.

PMID- 7512937
TI  - IHF supresses the inhibitory effect of H-NS on HU function in the hin inversion
      system.
AB  - In the hin-mediated DNA inversion system, HU facilitates formation of the
      synaptic complex composed of two recombination sites spaced 996 bp apart and of
      the enhancer situated between them, by looping the DNA as to promote interaction
      of Hin invertase with the Fis enhancer factor [Johnson et al., Nature 329 (1987)
      462-465]. The HU requirement for the in vivo hin-mediated inversion was
      demonstrated previously [Wada et al., Gene 76 (1989) 345-352; Hillyard et al., J.
      Bacteriol. 172 (1990) 5402-5407; Haykinson and Johnson, EMBO J. 12 (1993) 2503
      2512] and in the current experiments. This HU action, however, required IHF when
      H-NS was present in the cell; i.e., the inversion reaction of the hin-invertible
      DNA fragment carried by the pKK1202R plasmid proceeded efficiently in host cells
      either deficient in H-NS or in the presence of both H-NS and IHF, but not in the
      cells depleted for IHF alone. The level of hin mRNA in mutant cells lacking HU or
      IHF, in which hin inversion did not occur, was normal or slightly increased. When
      IHF was absent, the stimulating effect of HU on in vitro DNA circle formation of
      a 125-bp hin fragment between hixL and the enhancer where Fis binds was inhibited
      by H-NS. The present study provides an example of a multi-component interaction
      between HU, H-NS and IHF on the hin DNA region, which contains three
      characteristic sites, a d(A/T)4 stretch and bent DNA site, and two putative IHF
      binding sites.

PMID- 7512939
TI  - Sequence of a bovine c-kit proto-oncogene cDNA.
AB  - The Kit protein is a cell-surface tyrosine kinase receptor encoded by the c-kit
      proto-oncogene. cDNA clones encoding a protein homologous to the mouse and human
      Kit were isolated from a bovine cerebrum cDNA library. The deduced amino-acid
      sequence shows 83 and 90% identity to the mouse and human Kit, respectively.

PMID- 7512938
TI  - Expression of the alpha 2-macroglobulin-encoding gene in rat brain and cultured
      astrocytes.
AB  - The alpha 2-macroglobulin (alpha 2M), a protease inhibitor, is a major acute
      phase protein in rats, and is produced in the liver during acute inflammation.
      Recently, it has been demonstrated that alpha 2M is also produced by cultured
      astrocytes from newborn rat brain and has neurite-promoting activity. Here, we
      found that the expression of the alpha 2M gene was significantly enhanced in the
      brain following intraperitoneal injection of the neurotoxicant, kainic acid (KA),
      suggesting that alpha 2M acts as an acute-phase protein in the brain, as in the
      case of the liver, and may be involved in neural repair processes. Expression of
      alpha 2M in cultured astrocytes was shown to be stimulated by interleukin-6 (IL
      6) and/or leukemia inhibitory factor (LIF) in the presence of glucocorticoid. The
      amount of mRNAs for IL-6 and LIF increased in the brain of KA-injected rats prior
      to alpha 2M induction. These results strongly suggested that IL-6 and LIF are
      involved in alpha 2M induction in the brain, as in the case of the liver.
      Analysis of the cis-acting element(s) and the trans-acting factor(s) suggested
      that the regulatory mechanism for alpha 2M expression in astrocytes was similar
      to that in inflamed liver.

PMID- 7512940
TI  - prostatic xanthoma: a mimic of prostatic adenocarcinoma.
AB  - Xanthoma is a localized collection of cholesterol-laden histiocytes that is
      usually idiopathic, but may be seen in patients with hyperlipidemia. We report
      seven cases of xanthoma involving the prostate, including one arising in a
      patient with mild hyperlipidemia. Prostatic xanthoma appeared as a solitary
      microscopic lesion in the peripheral zone (six cases) or transition zone (one
      case). One needle biopsy specimen with xanthoma was initially interpreted as well
      differentiated adenocarcinoma with a clear cell (hypernephroid) pattern, but
      immunohistochemical studies revealed the histiocytic nature of the proliferation.
      Five cases (three needle biopsy specimens and two retropubic prostatectomy
      specimens) contained a solitary xanthoma adjacent to foci of adenocarcinoma.
      Another xanthoma was present in a transurethral resection specimen with nodular
      hyperplasia. Although unusual, xanthoma should be considered in the differential
      diagnosis of clear cell adenocarcinoma and other clear cell proliferations of the
      prostate, particularly in limited tissue samples, such as from needle biopsies
      and transurethral resections.

PMID- 7512941
TI  - Nephrogenic adenoma of the prostatic urethra involving the prostate gland: a
      clinicopathologic and immunohistochemical study of eight cases.
AB  - Nephrogenic adenoma (NA) of the prostatic urethra with involvement of the
      prostate gland can mimic other small-gland proliferations of the prostate,
      particularly adenocarcinoma of the prostate. To further characterize this lesion
      and refine diagnostic criteria we retrospectively reviewed the clinicopathologic
      features and immunohistochemical findings of eight cases of NA involving the
      prostate gland seen at The University of Texas M.D. Anderson Cancer Center from
      1987 to 1992. The patients' ages ranged from 44 to 76 years (average age, 65
      years). Six patients had lower genitourinary tract operations. Follow-up
      information was available for six patients (follow-up period, 5 to 38 months);
      only one patient had clinical evidence of recurrence (5 months after surgery).
      The remaining patients were alive and well with no evidence of disease.
      Histologically, NA was characterized by a proliferation of small tubules lined by
      a single layer of cuboidal or flattened cells with clear or eosinophilic
      cytoplasm. The nuclei were round with fine chromatin and there was no mitotic
      activity. Nucleoli were generally small, but occasionally prominent. All NA
      extended into the prostatic parenchyma, raising the possibility that these
      lesions may represent prostatic small-gland proliferations, particularly prostate
      adenocarcinoma. However, all cases tested were negative for prostate-specific
      antigen and prostatic acid phosphatase. Our findings indicate that the histologic
      features and the use of prostate-specific antigen and prostatic acid phosphatase
      immunostains will help to distinguish NA of the urethra involving the prostate
      from other small-gland proliferations (eg, small-acinar adenocarcinoma of the
      prostate, clear cell adenocarcinoma of the urethra, sclerosing adenosis, atypical
      adenomatous hyperplasia, florid hyperplasia of mesonephric remnants, simple
      lobular atrophy, and incomplete basal cell hyperplasia).

PMID- 7512944
TI  - Reattachment of retinas to cultured pigment epithelial monolayers from Xenopus
      laevis.
AB  - PURPOSE: The authors aimed to establish an in vitro model of the retinal pigment
      epithelium (RPE) suitable for studies of neural retina-epithelium interactions.
      METHODS: Sheets of RPE were obtained from Xenopus laevis eyes by Dispase
      treatment of intact globes. After dispersal in trypsin-EDTA solution, cells were
      plated onto Matrigel-coated microporous membrane filters and grown in a serum
      free defined medium. RESULTS: Confluent cell monolayers obtained after 7 to 10
      days of culture appeared by electron microscopy to be morphologically polarized,
      established junctional complexes, and exhibited transepithelial resistances
      ranging from 300 to 500 omega.cm2. As did the native epithelium, these cells
      formed cytoskeletons consisting of circumferential bands of actin myofilaments at
      their periphery and whorls of cytokeratin intermediate filaments throughout the
      cytoplasm. Co-culture of freshly isolated neural retinas with monolayers resulted
      in the apparent reattachment of photoreceptors to the RPE within 3 hours.
      CONCLUSIONS: Primary cultures of amphibian RPE that express phenotypic
      characteristics of the epithelium in situ are also capable of establishing
      adhesive interactions with isolated neural retinas.

PMID- 7512942
TI  - Retinoic acid regulates clonal growth and differentiation of cultured limbal and
      peripheral corneal epithelium.
AB  - PURPOSE: To determine if vitamin A could be one of the factors in serum
      responsible for the previously observed effect of 20% fetal bovine serum on
      stimulating clonal growth of an additional subpopulation in limbal cultures,
      possibly stem cells, but inhibiting that of transient amplifying cells in
      peripheral corneal cultures. METHODS: A reported serum-free clonal growth assay
      was used. The mitogenic response was measured by colony-forming efficiency (CFE),
      colony size, and BrdU labeling index; the differentiation was assessed by colony
      morphology, AE-5 monoclonal antibody staining, and cornified envelope formation.
      RESULTS: HPLC analyses revealed that added retinoic acid (RA) was rapidly taken
      up by cultured cells. As compared to the control without RA, low concentrations
      of RA (10(-9) M to 10(-7) M) stimulated the CFE of limbal cultures but did not
      change that of peripheral corneal cultures. Furthermore, 10(-8) M RA induced the
      emergence of two new types of colonies, one of which was almost exclusively
      present in limbal cultures, and allowed continuous clonal growth of some colonies
      in late limbal cultures. RA also dose dependently reduced colony size and BrdU
      labeling index in both limbal and peripheral corneal cultures. RA in
      concentrations above 10(-8) M stimulated normal differentiation of both limbal
      and peripheral corneal epithelial cells, as evidenced by increased AE-5 staining,
      but inhibited the formation of cornified envelopes, an index for abnormal,
      squamous metaplasia, in late cultures. CONCLUSION: These results suggest that RA
      has a differential dose-dependent effect on subpopulations of corneal and limbal
      epithelial cells. Although RA stimulates the conversion of limbal stem cells to
      transient amplifying cells, it inhibits the amplification of corneal and limbal
      transient amplifying cells and prevents abnormal terminal differentiation. These
      data further support the role of vitamin A as a physiological modulator of
      proliferation and differentiation of the ocular surface epithelium.

PMID- 7512945
TI  - Relaxation of trabecular meshwork and ciliary muscle by release of nitric oxide.
AB  - PURPOSE: Recent evidence suggests that nitric oxide (NO) is a major messenger
      molecule regulating smooth muscle contractility. A role for NO in aqueous humor
      dynamics, and thus regulation of intraocular pressure, has been postulated.
      Recently, we described contractile properties of isolated bovine trabecular
      meshwork and ciliary muscle strips. To assess whether vasodilators contribute to
      the regulation of trabecular meshwork and ciliary muscle contractility, we
      measured the effect of various substances known to induce vasodilation by
      increasing intracellular cGMP production. METHODS: Measurements of isometric
      tension were performed on isolated bovine ciliary muscle and trabecular meshwork
      strips using a custom-built electromagnetic force-length transducer. The effects
      of a membrane-permeable cGMP and an inhibitor of nitric oxide formation (L
      nitroarginine = L-NAG) were investigated. Organic nitrate (isosorbide dinitrate =
      ISDN, isosorbide-5-mononitrate = 5-ISMN) and non-nitrate (sodium nitroprusside =
      SNP, S-nitroso-N-acetyl penicillamine = SNAP) vasodilators were tested. RESULTS:
      Isolated strips were precontracted by carbachol 10(-6) mol/l for 30 minutes (100%
      carbachol maximal contraction). 8-bromo-cGMP 10(-4) mol/l evoked a relaxation to
      86.7% +/- 1.4% (n = 8) in ciliary muscle and 58.6% +/- 5.4% (n = 7) in trabecular
      meshwork. Inhibition of NO-synthase by L-NAG increased the carbachol-induced
      contraction. The organic nitrovasodilators ISDN and 5-ISMN produced significant
      relaxations. The non-nitrates SNP and SNAP were the most potent relaxants. SNP
      10(-4) mol/l relaxed the isolated ciliary muscle to 55.5% +/- 3.5% and the
      trabecular meshwork to 38.6% +/- 3.6%. ISDN and SNP were also tested on isolated
      strips without carbachol-induced precontraction. Both vasodilators had
      significant relaxing activity under these conditions. CONCLUSION: The data
      indicate that an increase of intracellular cGMP by application of cGMP and
      organic nitrate or non-nitrate vasodilators induces relaxation of the bovine
      trabecular meshwork and ciliary muscle. Thus, nitric oxide is a cotransmitter of
      smooth muscle relaxation in the chamber angle and may be involved in the
      regulation of aqueous humor dynamics.

PMID- 7512943
TI  - Visual deprivation upregulates extracellular matrix synthesis by chick scleral
      chondrocytes.
AB  - PURPOSE: To characterize the cellular events responsible for the exaggerated
      ocular growth associated with experimental myopia in chicks, the accumulation and
      synthesis of proteoglycans and collagen were measured in the posterior sclera of
      control and form vision-deprived chick eyes. METHODS: Buttons (10 mm) from the
      posterior sclera of control and deprived eyes were used for biochemical
      measurements of glycosaminoglycans and hydroxyproline to estimate proteoglycan
      and collagen accumulation, respectively. The synthesis of proteoglycan, collagen,
      total protein, and RNA were measured in cultures of scleral chondrocytes isolated
      from posterior scleral buttons of control and deprived eyes by measuring the
      specific incorporation of 35SO4, [3H]proline, [35S]methionine, and [5-3H]uridine,
      respectively. The relative rate of aggrecan precursor protein synthesis was
      measured in cultures of control and deprived chondrocytes using
      immunoprecipitation assays. RESULTS: Form deprivation resulted in increased
      accumulation of proteoglycans but not collagen within the posterior sclera. In
      contrast, chondrocytes isolated from the posterior sclera of form-deprived eyes
      maintained elevated rates compared with controls of proteoglycan synthesis
      (+143%) and collagen synthesis (155%), as well as total protein synthesis (115%)
      and total RNA synthesis (44%). Because total protein synthesis was higher in
      cultures of deprived chondrocytes, the rate of aggrecan precursor protein
      synthesis, relative to total protein synthesis, was similar for both populations
      of cells. Pretreatment of scleral chondrocytes with actinomycin D, an inhibitor
      of RNA synthesis, resulted in a 112% increase in the rate of proteoglycan
      synthesis by control chondrocytes, but had no significant effect on the rate of
      proteoglycan synthesis by chondrocytes isolated from form-deprived eyes.
      CONCLUSIONS: Because proteoglycans accumulate within the posterior sclera of
      deprived eyes to a greater extent than collagen, yet form deprivation stimulates
      the synthesis of collagen and total protein as well as proteoglycans, these data
      suggest that collagen, and perhaps other scleral components, are selectively
      remodeled within the posterior sclera during the process of ocular elongation.
      Furthermore, experiments with actinomycin D suggest that the general upregulation
      observed in form-deprived chondrocytes may be due to the absence of a inhibitor
      normally present under conditions of form vision.

PMID- 7512947
TI  - Expression of phototransduction cascade genes in the ground squirrel retina.
AB  - PURPOSE: This study describes the expression and distribution of
      phototransduction cascade gene products in the cone-dominant retina of the ground
      squirrel Spermophilus tridecemlineatus. METHODS: Messenger RNA expression was
      studied by blot hybridization, and the distribution of the gene products was
      investigated by immunocytochemistry. RESULTS: RNA blot hybridization showed
      messages for the alpha 2, beta 1, and beta 3 subunits of transducin but was
      negative for rhodopsin, alpha 1-transducin, and the alpha, beta, and gamma
      subunits of cyclic guanosine monophosphate (cGMP) phosphodiesterase.
      Immunocytochemical labeling indicated that the approximate ratio of the
      photoreceptor types in ground squirrel retina is 90.6% for green cones, 6.3% for
      rod-like cells, and 3.1% for blue cones. Rod-like cells were immunopositive for
      rhodopsin and blue opsin. All photoreceptor elements were labeled by antibodies
      against alpha 1-transducin (which recognizes both the alpha 1 and alpha 2
      isoforms), beta 3-transducin, and the rod gamma subunit of phosphodiesterase,
      whereas no cells were labeled by antibodies against the rod alpha and beta
      subunits of phosphodiesterase or against the rod cGMP-gated cation channel. Rod
      like cells and blue cones were stained by antibodies against beta 1-transducin.
      CONCLUSIONS: The authors demonstrate new cone-like traits in the biochemical make
      up of rod-like cells, and a distribution of the transducin beta subunit in the
      ground squirrel is different from that found in other mammals.

PMID- 7512946
TI  - Molecular and biochemical analyses of iodopsin in rd chick retina.
AB  - PURPOSE: The results of previous immunocytochemical and electrophysiological
      studies of retinas of rd (retinal degeneration) chicks suggest that the iodopsin
      cone visual pigment may be defective in this mutant. The goal of this study was
      to determine if the primary structure and synthesis of this protein is normal in
      this animal model of inherited retinal degeneration. METHODS: Northern cDNA
      sequence and western analyses were used to study rd/rd iodopsin. cDNAs encoding
      rd/rd iodopsin were obtained by screening an rd/rd cDNA retinal expression
      library and by reverse transcription PCR. Western blots were probed with either
      R4 or COS-1, two different monoclonal antibodies that have been shown to
      specifically recognize chicken iodopsin. RESULTS: Hybridization of the +/+, +/rd,
      and rd/rd poly(A)+ RNA with an iodopsin cDNA probe revealed the presence of a
      single 1.5 kb band in each of the samples, all of which were labeled with equal
      intensity. No significant differences were found between the published nucleic
      acid sequences for normal chicken iodopsin cDNA and that determined for rd/rd
      iodopsin cDNA. Antibody-dependent differences in the staining intensity of the 34
      kDa band containing iodopsin were observed on western blots of +/+, +/rd, and
      rd/rd retinal protein. R4 stained the 34 kDa band in each sample with equal
      intensity. COS-1 labeling of the 34 kDa band in the rd/rd sample was less intense
      than that observed in the +/+ and +/rd samples. CONCLUSIONS: Based on the results
      of the cDNA sequence and northern blot experiments, the authors conclude that the
      gene encoding iodopsin and transcription of this gene are normal in the rd
      mutant. The results of the western blot analyses of rd/rd iodopsin suggest that
      post-translational processing of iodopsin may be abnormal in this mutant.

PMID- 7512948
TI  - Substance P-containing axon terminals in the mucosa of the human urinary bladder:
      pre-embedding immunohistochemistry using cryostat sections for electron
      microscopy.
AB  - The ultrastructure of substance P (SP)-containing axon terminals in the mucosa of
      the human urinary bladder was studied. Numerous SP-immunoreactive varicose nerve
      fibers were seen in the lamina propria, and most of them ran freely in the
      connective tissue. Many SP-immunoreactive nerve fibers were observed beneath the
      epithelium, and perivascular SP-immunoreactive nerves were also found in the
      submucosal layer. We observed a total of 305 SP-immunoreactive (IR) axon
      terminals, of which most (89.6%) were free nerve endings at the ultrastructural
      level; the rest of the SR-IR axon terminale were seen in the vicinity of the
      epithelium and blood vessels in the lamina propria. Varicose regions of SP-IR
      axon terminals contained large granular and small agranular synaptic vesicles,
      and most of them partially lacked a Schwann cell sheath. In some SP-IR
      varicosities, synaptic vesicles were concentrated in the region without any
      Schwann cell sheath. Long storage (for more than 1 month) of fixed-tissue pieces
      in sucrose before freezing has improved the ultrastructure of cryostat sections
      in pre-embedding immunohistochemistry. Trypsin digestion for the purpose of
      exposing antigenic sites was also employed before applying the first antiserum.

PMID- 7512949
TI  - A single protocol to detect transcripts of various types and expression levels in
      neural tissue and cultured cells: in situ hybridization using digoxigenin
      labelled cRNA probes.
AB  - We have developed a simple non-radioactive in situ hybridization procedure for
      tissue sections and cultured cells using digoxigenin-labelled cRNA probes. This
      protocol can be applied for the detection of various transcripts present at a
      wide range of expression levels in the central nervous system. Cerebellar
      hybridization signals for transcripts estimated to be expressed at high (MBP,
      myelin basic protein), moderate (GluR1, subunit of AMPA/kainate sensitive
      glutamate receptors) and low (inositol polyphosphate-5-phosphatase) levels of
      abundance are demonstrated as examples. The sensitivity and cellular resolution
      were significantly improved by avoiding any ethanol treatment commonly used in
      other procedures. The localization of a labelled cell with respect to its
      environment is shown to be more easily assessed by counterstaining of the tissue
      with the nuclear dye Hoechst 33258. The present protocol can be combined with
      immunocytochemistry as demonstrated for glial fibrillary acidic protein (GFAP).
      All steps of the procedure, including preparation and labelling of the cRNA
      probes, pretreatment of tissue, hybridization and visualization of the labelled
      transcripts, are described in detail.

PMID- 7512950
TI  - Subunit b of cholera toxin labels interstitial cells of Cajal in the gut of rat
      and mouse.
AB  - Cholera toxin subunit b was found in vivo and in vitro to label interstitial
      cells of Cajal in the intestine of rat and mouse. Cholera toxin-labelled
      interstitial cells were present in the subserosa, the myenteric plexus and the
      deep muscular plexus of mouse small intestine, and the deep muscular plexus only
      of the rat small intestine. In the large intestine of the mouse, interstitial
      cells were present in the subserosa and in a plexus associated with the inner
      surface of the circular muscle, while in the rat they were only present in the
      latter location. Macrophages, which were present in many of the same locations as
      interstitial cells, were also labelled by cholera toxin but could be
      distinguished from interstitial cells by their ability to take-up fluorescein
      isothiocyanate-labelled dextran. Labelling with subunit b of cholera toxin is a
      simple way of labelling interstitial cells of Cajal and which is compatible with
      a range of physiological and histological procedures.

PMID- 7512951
TI  - Identification of covalently bound amino-terminal myristic acid in endothelial
      nitric oxide synthase.
AB  - Endothelial nitric oxide synthase (eNOS) is unique among the nitric oxide
      synthase family of proteins due to the presence of an N-myristoylation consensus
      sequence elucidated from the cloning of its cDNA. Although eNOS was metabolically
      labeled with [3H]myristic acid and mutation of glycine 2 in the N-myristoylation
      consensus sequence changed the particulate localization of the enzyme to a
      cytosolic form, the definitive characterization of eNOS as an N-myristoylprotein
      has not been demonstrated. Therefore, the purpose of the present study was to
      determine the nature of the fatty acid incorporated into eNOS. Wild-type or G2A
      mutant (mutation of glycine 2, the myristic acid acceptor site, to alanine) eNOS
      transfected COS cells and bovine aortic endothelial cells (BAEC) were
      metabolically labeled with [3H]myristic acid for 5 h. The radiolabel was
      primarily incorporated into membrane-associated eNOS from wild-type transfected
      COS cells and cultured BAEC but not into the mutant eNOS from G2A-transfected COS
      cells. Qualitatively similar amounts of immunoreactive protein were found in wild
      type and G2A-transfected cells. In addition, linkage of the radiolabel to eNOS
      was insensitive to hydroxylamine treatment, and incorporation of the radiolabel
      into eNOS was abolished by cyclo-heximide. Chemical analysis of the fatty acid
      released by acid methanolysis of labeled eNOS verified the 3H-labeled fatty acid
      as protein-bound myristic acid. These results unequivocally demonstrate that eNOS
      incorporates myristic acid via an amide linkage with the amino-terminal glycine
      of the enzyme as a co-translational modification.

PMID- 7512952
TI  - Genetic evidence supporting the role of peroxisome assembly factor (PAF)-1 in
      peroxisome biogenesis. Polymerase chain reaction detection of a missense mutation
      in PAF-1 of Chinese hamster ovary cells.
AB  - The peroxisome/plasmalogen-deficient Chinese hamster ovary (CHO) mutant cell line
      ZR-78.1 contains a missense mutation in its cDNA-encoding peroxisome assembly
      factor-1 (PAF-1). Using a rapid polymerase chain reaction assay, we now
      demonstrate that the genome of ZR-78.1 contains only the mutant allele. When
      mutant ZR-78.1 is fused with wild-type karyoplasts, occasional "negative nuclear
      hybrids" are observed that lack peroxisomes (Allen, L.-A. H., Morand, O. H., and
      Raetz, C. R. H. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 7012-7016). Despite the
      fact that negative nuclear hybrids are tetraploid, they do not contain the wild
      type PAF-1 gene, suggesting that a chromosome fragment bearing the wild-type copy
      of PAF-1 was lost. Negative nuclear hybrids reconstituted with wild-type
      cytoplasts do contain a wild-type PAF-1 gene, indicating that the cytoplasts
      somehow reintroduced the wild-type PAF-1 allele without increasing ploidy. These
      findings support the role of PAF-1 and exclude the hypothesis of an additional
      cytoplasmic requirement for reinitiation of peroxisome biogenesis in peroxisome
      deficient CHO cells. The plasmalogen deficiency and some other biochemical
      properties of ZR-78.1 are partially corrected in 5-azacytidine-treated subclones.
      However, such pseudo-revertants do not contain peroxisomes, consistent with the
      fact that there is no wild-type PAF-1 gene to reactivate by demethylation.

PMID- 7512954
TI  - Regulation of tetrahydrobiopterin biosynthesis in cultured dopamine neurons by
      depolarization and cAMP.
AB  - Primary cultures containing embryonic rat brain mesencephalic or hypothalamic
      dopamine neurons were used to examine the effects of membrane depolarization and
      elevations of cAMP levels on tetrahydrobiopterin cofactor content. Initial
      studies showed that 24-h incubations with 8-bromo-cAMP or isobutyl methylxanthine
      increased cofactor levels in either culture system, whereas the stimulatory
      effects of forskolin or depolarization of membrane potential were only observed
      in cultures of hypothalamus. 8-Bromo-cAMP was found to increase cofactor content
      in a concentration-dependent manner, with increases observed up to 5 mM. The time
      course of the effect of 8-bromo-cAMP was biphasic. Over the short term, an
      increase of 50% in cofactor content at 2 and 5 h was detected. Over the long
      term, by 24-48 h, cofactor levels increased by between 100% and 300%. Studies of
      cofactor turnover indicated that the long-term increase was due to stimulation of
      tetrahydrobiopterin biosynthesis with no alteration in degradation rate.
      Inhibitors of gene transcription and translation prevented the long- but not
      short-term increase in cofactor content. Levels of GTP cyclohydrolase I mRNA were
      increased 7-10-fold following 5 h of incubation with 8-bromo-cAMP.
      Tetrahydrobiopterin biosynthesis within cultured dopamine neurons of the
      hypothalamus and mesencephalon thus appears to be regulated by a cAMP-dependent
      mechanism involving enhanced gene expression of enzyme(s) involved in cofactor
      biosynthesis.

PMID- 7512953
TI  - D4 dopamine receptor-mediated signaling events determined in transfected Chinese
      hamster ovary cells.
AB  - A Chinese hamster ovary (CHO) cell line stably expressing a recombinant human D4
      dopamine receptor made from a synthetic gene has been used to determine potential
      D4-mediated signaling events. We designed and synthesized a modified gene coding
      for a human D4 receptor with reduced G + C content but unaltered encoded amino
      acids. Stable expression of this gene was obtained in two cell lines, inducible
      expression in CHO lacI cells and constitutive expression in HEK293 cells. In CHO
      lacI cells induced to express D4 receptors but not in uninduced cells, dopamine
      and quinpirole inhibit forskolin-stimulated cAMP accumulation and potentiate ATP
      stimulated [3H]arachidonic acid release through a mechanism that requires protein
      kinase C but is unaffected by membrane-soluble cAMP analogs. In addition, D4
      receptor activation causes an increase in the rate of extracellular acidification
      measured by microphysiometry. This response is unaffected by protein kinase C
      down-regulation but is inhibited by removal of extracellular sodium and
      inhibitors of NaH-1 exchange, suggesting the involvement of a Na+/H+ exchanger.
      All responses are blocked by clozapine and are sensitive to pertussis toxin. D4
      receptors, like other G(i)/G(o)-linked receptors, mediate multiple signaling
      events, and the pathways activated are similar to those used by D2 and D3
      receptors expressed in similar cells.

PMID- 7512955
TI  - Functional characterization of the Escherichia coli glycerol facilitator, GlpF,
      in Xenopus oocytes.
AB  - The glycerol facilitator of Escherichia coli, GlpF, is a putative nonselective
      transport channel in the inner membrane of this Gram-negative bacterium. It is a
      member of the major intrinsic protein (MIP) family of transmembrane channel
      proteins. Its characterization has been hampered by the lack of a heterologous
      test system in which its activity can be examined in the absence of other
      bacterial proteins. Transport of glycerol mediated by this protein was
      characterized following injection of glpF mRNA into Xenopus laevis oocytes. The
      properties of GlpF were compared with those of the homologous plant water channel
      protein, gamma tonoplast intrinsic protein (gamma TIP), as well as the
      nonhomologous Xenopus K+ channel, Xsha. GlpF selectively transported glycerol but
      not water or ions, while gamma TIP and Xsha were specific for water and K+,
      respectively. Voltage clamp experiments showed that GlpF was not voltage
      activated for ion transport. Glycerol transport via GlpF proved to be
      nonsaturable up to 200 mM and exhibited a low temperature of activation (Ea = 4.5
      kcal/mol), consistent with the conclusion of Heller et al. (Heller, K. B., Lin,
      E. C. C., and Wilson, T. H. (1980) J. Bacteriol. 144, 274-278) that GlpF mediates
      glycerol diffusion via a pore type mechanism. GlpF-mediated transport of glycerol
      was blocked by mercuric ions (Hg2+) but not N-ethylmaleimide. The inhibitory
      effect of Hg2+ was partially prevented by inclusion of a high concentration of
      glycerol and reversed by mercaptoethanol. The results serve to characterize the
      transport properties of the E. coli glycerol facilitator.

PMID- 7512957
TI  - Design of structure-based reverse transcriptase inhibitors.
AB  - Based on the crystallographic structure of the active site in the reverse
      transcriptase (RT) of human immunodeficiency virus (HIV), a group of hydrophobic
      polyadenylic acid (5') derivatives were designed and synthesized as inhibitors of
      the enzyme. These compounds were found to inhibit all six of the RTs tested, with
      IC50 = 10(-11)-10(-8) M, but did not inhibit either RNA polymerase II (even at
      10(-5) M) or DNA polymerase I up to 10(-6) M inhibitor concentration. The
      underivatized poly(A) did not inhibit any of the RTs tested under the same
      conditions. In aqueous solutions of purified HIV-1 RT, poly-2'-O-(2,4
      dinitrophenyl)-oligo(A) was found to inhibit the enzyme reversibly and compete
      with the primer-template poly(A)-(dT)12, whereas poly-2'-O-(3-fluoro-4,6
      dinitrophenyl)-poly(A) was found to inactivate HIV-1 RT irreversibly by covalent
      labeling. A comparison of physicochemical properties of the hybrids poly(A)
      poly(dT) and dinitrophenyl-poly(A)-poly(dT) shows that the hydrophobic
      dinitrophenyl groups stabilize double helical structures. These inhibitors were
      also found to be effective in keeping susceptible lymphocytes viable in the
      presence of HIV-1 (wild type). The effective inhibitor concentrations (EC50) were
      found to be 0.2-2.6 microgram/ml. No toxic effect on the host cells was found
      even at 100-1000-fold higher inhibitor concentrations.

PMID- 7512956
TI  - Insulin stimulates phosphorylation of c-Jun, c-Fos, and Fos-related proteins in
      cultured adipocytes.
AB  - In differentiated 3T3-F442A adipocytes, insulin stimulated rapid and transient
      phosphorylation of c-Jun. Insulin also stimulated phosphorylation of c-Fos and
      several Fos-related proteins (pp72, pp45, and pp39) as indicated by precipitation
      with anti-c-Fos antibody following exposure to denaturating conditions.
      Phosphorylation of c-Fos was stimulated by 7-fold by 60 min, while
      phosphorylation of Fos-related proteins reached maxima of 3.5-5.5-fold at 15 to
      60 min. The increase in phosphorylated c-Fos was due to an increase in both c-Fos
      protein and the stoichiometry of c-Fos phosphorylation, and was not observed in c
      fos (-/-) cells. Additionally, insulin stimulated phosphorylation of a protein
      with molecular mass of approximately 82 kDa on tyrosine residues by 2.5-fold
      within 30 min; this protein appeared to be immunologically related to c-Fos.
      These increases in the phosphorylation of AP-1 transcription factors correlated
      with a > 5-fold stimulation of expression of a 12-O-tetradecanoylphorbol-13
      acetate-responsive element-chloramphenicol acetyltransferase reporter gene
      transiently transfected into 3T3-F442A cells. These results indicate that insulin
      stimulates the phosphorylation of AP-1 transcription factors and several Fos
      related proteins on serine and tyrosine residues. This is associated with changes
      in AP-1-mediated gene expression in vivo, suggesting that AP-1 phosphorylation by
      insulin plays a role in insulin-regulated gene expression.

PMID- 7512959
TI  - Clustering of the high affinity Fc receptor for immunoglobulin G (Fc gamma RI)
      results in phosphorylation of its associated gamma-chain.
AB  - We are investigating the role of gamma-chain in functions mediated by the high
      affinity Fc receptor for IgG (Fc gamma RI). In a previous study, we found that
      gamma-chain, which is a member of the family of zeta-chain proteins, associates
      with Fc gamma RI. Here we show that clustering of Fc gamma RI leads to a rapid
      and transient tyrosine phosphorylation of gamma-chain in U937 cells. The response
      was limited to Fc gamma RI activation, and no phosphorylation of gamma-chain was
      observed after cross-linking of monoclonal antibodies to other surface receptors
      on these cells. The gamma-chain phosphorylated after Fc gamma RI clustering was
      the gamma-chain associated with the receptor. We also identified Syk as one of
      the kinases associated with the receptor complex. Upon Fc gamma RI activation,
      Syk, but not ZAP-70, was phosphorylated, and reimmunoadsorption experiments of
      phosphoproteins from immune complex in vitro kinase assays indicated that Syk is
      part of the activated gamma-chain-Fc gamma RI complex. These results suggest that
      gamma-chain links Fc gamma RI to intracellular transduction pathways.

PMID- 7512961
TI  - Immunoaffinity purification of the Escherichia coli rne gene product. Evidence
      that the rne gene encodes the processing endoribonuclease RNase E.
AB  - The rne gene product was highly purified from Escherichia coli cells
      overproducing the protein by a procedure including immunoaffinity chromatography.
      Expression in vivo and in vitro of the cloned 6-kilobase pair DNA fragment
      containing the entire rne gene resulted in the synthesis of a protein migrating
      as a 180-kDa polypeptide in the SDS-polyacrylamide gel. The position of the
      protein on the two-dimensional polyacrylamide gel indicated that the protein is
      highly acidic. The enzymatic activity test which used as the substrate RNA I and
      9 S RNA provided evidence that the rne gene is the structural gene for the RNA
      processing enzyme RNAse E. The Western blot analysis performed using a rabbit
      antiserum raised against a truncated 110-kDa protein fragment of RNase E
      (containing two-thirds of the sequence from the N terminus) revealed that the 180
      kDa polypeptide is the only protein recognized by the antibodies in a wild type
      whole cell extract of E. coli. The antibodies cross-reacted with similar
      molecular weight proteins from a number of different bacteria, suggesting that
      the rne gene product is evolutionarily conserved in the bacterial world.

PMID- 7512960
TI  - Interactions with tenascin and differential effects on cell adhesion of neurocan
      and phosphacan, two major chondroitin sulfate proteoglycans of nervous tissue.
AB  - We have studied interactions of tenascin with two chondroitin sulfate
      proteoglycans, neurocan and phosphacan. Neurocan is a multi-domain proteoglycan
      with a 136-kDa core protein that is synthesized by neurons and binds to
      hyaluronic acid, whereas the 173-kDa core protein of phosphacan, which is
      synthesized by glia, represents an extracellular variant of the receptor-type
      protein tyrosine phosphatase RPTP zeta/beta. Keratan sulfate-containing
      glycoforms of phosphacan (designated phosphacan-KS) are also present in brain.
      Immunocytochemical studies of early postnatal rat cerebellum demonstrated that
      the localization of neurocan, phosphacan, and phosphacan-KS all overlap
      extensively with that of tenascin, an extracellular matrix protein that modulates
      cell adhesion and migration. Binding studies using purified proteins covalently
      attached to fluorescent microbeads demonstrated that proteoglycan-coated beads co
      aggregated with differently fluorescing beads coated with tenascin. The co
      aggregation was specifically inhibited by Fab' fragments of antibodies against
      tenascin or the proteoglycans and by soluble neurocan, phosphacan, and tenascin.
      A solid phase radioligand binding assay confirmed that neurocan, phosphacan, and
      phosphacan-KS bind to tenascin but not to laminin and fibronectin. Chondroitinase
      treatment of the proteoglycans or addition of free chondroitin sulfate had no
      significant effect, indicating that the binding activity is mediated largely via
      the core glycoproteins. Scatchard analysis demonstrated high affinity binding of
      125I-phosphacan, phosphacan-KS, and neurocan to a single site in tenascin, and
      neurocan and various glycoforms of phosphacan all inhibited binding of 125I
      phosphacan to tenascin. In studies of cell adhesion to proteins adsorbed to Petri
      dishes, phosphacan inhibited adhesion of C6 glioma cells to tenascin whereas
      neurocan had no effect. Our results suggest that tenascin binds phosphacan and
      neurocan in vivo and that interactions between chondroitin sulfate proteoglycans
      and tenascin may play important roles in nervous tissue histogenesis, possibly by
      modulating signal transduction across the plasma membrane.

PMID- 7512958
TI  - Product of the steel locus suppresses apoptosis in hemopoietic cells. Comparison
      with pathways activated by granulocyte macrophage colony-stimulating factor.
AB  - Steel factor (SF), also referred to as Kit ligand, stem cell factor, or mast cell
      growth factor, is essential for the development of hematopoietic stem cells in
      vivo. It is shown here that SF is mainly a survival factor for hemopoietic cells
      with little if any proliferative effect. In contrast, granulocyte macrophage
      colony-stimulating factor (GM-CSF) acts both as a survival factor and as a potent
      growth factor. We have probed the pathways activated by SF and GM-CSF in
      suppression of active cell death (apoptosis) using two classes of inhibitors:
      Tyrphostins that are specific inhibitors of protein tyrosine kinase, and
      amiloride derivatives (5-(N,N-ethyl-n-isopropyl)amiloride and 5-(N,N
      hexamethylene)amiloride) that have been designed as specific inhibitors of the
      Na+/H+ antiporter. Both SF-dependent and GM-CSF-dependent pathways are sensitive
      to inhibition by Tyrphostins with, nonetheless, a quantitative difference. All
      Tyrphostins tested are more potent inhibitors of c-Kit than of GM-CSF receptor
      triggered pathways, the most striking being Tyrphostin B42 that is 10 times more
      potent. In contrast to the discrepancy in Tyrphostin dose-response curves,
      titration curves for 5-(N-ethyl-n-isopropyl)amiloride and 5-(N,N
      hexamethylene)amiloride are comparable in SF- or GM-CSF-stimulated cells.
      Furthermore, SF induces a rapid and sustained alkalinization of the intracellular
      pH, as assessed with the pH-sensitive probe 2',7'-bis(2-carboxyethyl)-5
      carboxyfluorescein. Taken together, our data indicate that input from two
      distinct pathways with discrepancy in immediate early events, that of c-Kit and
      GM-CSF receptor, results in a common output, activation of the Na+/H+ antiporter
      and suppression of apoptosis by the two ligands.

PMID- 7512963
TI  - Insulin stimulates the phosphorylation of Tyr538 and the catalytic activity of
      PTP1C, a protein tyrosine phosphatase with Src homology-2 domains.
AB  - PTP1C is a non-transmembrane protein-tyrosine phosphatase and contains two Src
      homology-2 (SH2) domains. Insulin stimulated the tyrosine phosphorylation of
      PTP1C in human 1M-9 lymphoblast cells, in rat H35 hepatoma cells and in Chinese
      hamster ovary cells over-expressing both insulin receptors and PTP1C. Insulin
      also stimulated the tyrosine phosphorylation of a mutant PTP1C lacking SH2
      domains in Chinese hamster ovary cells, suggesting that the SH2 domains are not
      required for insulin-stimulated tyrosine phosphorylation of PTP1C. The insulin
      receptor tyrosine kinase catalyzed the tyrosine phosphorylation of PTP1C in a
      cell-free system. Peptide mapping of phosphorylated PTP1C showed that Tyr538 in
      the C-terminal region was phosphorylated in response to insulin. The tyrosine
      phosphorylation of PTP1C by the insulin receptor kinase increased phosphatase
      activity. Furthermore, PTP1C was shown to bind to autophosphorylated insulin
      receptors through its C-terminal region, but PTP1C did not bind to
      unphosphorylated receptors. These results suggest that PTP1C is a target protein
      for the insulin receptor tyrosine kinase and that the C-terminal region of PTP1C
      may function both in the regulation of phosphatase activity and in the
      association of PTP1C with autophosphorylated insulin receptors.

PMID- 7512964
TI  - RNA splicing regulates the activity of a SH2 domain-containing protein tyrosine
      phosphatase.
AB  - A cDNA which encodes a protein tyrosine phosphatase with two src homology 2 (SH2)
      domains was isolated from a rat brain cDNA library. This phosphatase appears to
      be a rat homologue of PTP1D based on its amino acid sequence. The gene is
      expressed in a variety of tissues, and its mRNA is enriched in the brain,
      skeletal muscle, and lung. An RNA splice variant (PTP1Di) was also isolated which
      has four additional amino acid residues (Ala-Leu-Leu-Gln) in the catalytic
      domain. The catalytic domains of PTP1D and PTP1Di were expressed in Escherichia
      coli as glutathione S-transferase fusion proteins and purified to near
      homogeneity. Whereas both PTP1D and PTP1Di had catalytic activity, the Vmax of
      PTP1Di relative to that of PTP1D was 8-fold lower for para-nitrophenylphosphate,
      20-fold lower for nicotinic acetylcholine receptor, and 14-fold lower for myelin
      basic protein. The Km values of PTP1Di were lower than those of PTP1D for both
      nicotinic acetylcholine receptor and myelin basic protein, suggesting a higher
      affinity of PTP1Di for a protein substrate. These two forms also differed in
      optimum pH for para-nitrophenylphosphate and sensitivity to the inhibitory
      effects of vanadate, molybdate, and spermidine. In order to see if this insert
      would affect the catalytic activity of other related phosphatases, the 4-amino
      acids were inserted in the corresponding region of the catalytic domain of PTP1C.
      Whereas both the wild type and PTP1Ci which contained the 4-amino acid insert
      dephosphorylated para-nitrophenylphosphate, nicotinic receptor, and myelin basic
      protein, the enzyme activity of PTP1Ci was only 11-24% of that of PTP1C wild
      type. These results demonstrate that the 4-amino acid insert in the catalytic
      domains of PTP1D down-regulates its phosphatase activity and suggests that RNA
      splicing may serve as a regulatory mechanism of protein tyrosine phosphatase
      activity.

PMID- 7512962
TI  - Cloning and expression of a cDNA for the human prostanoid IP receptor.
AB  - A cDNA clone coding for a functional human prostanoid IP receptor has been
      isolated from a lung cDNA library. The human IP receptor consists of 386 amino
      acid residues with a predicted molecular mass of 40,961, and has the seven
      putative transmembrane domains characteristic of G-protein-coupled receptors.
      Challenge of Xenopus oocytes co-expressing the IP receptor and the cystic
      fibrosis transmembrane conductance regulator (cAMP-activated Cl- channel) with
      the stable prostacyclin analog iloprost resulted in specific inward Cl- currents,
      demonstrating that the cDNA encoded a functional IP prostanoid receptor coupled
      to elevation in cAMP. Radioreceptor binding studies using membranes prepared from
      mammalian COS cells transfected with the IP receptor cDNA showed that the rank
      order of potency for prostaglandins and prostaglandin analogs in competition for
      [3H]iloprost specific binding sites was as predicted for the IP receptor, with
      iloprost >> carbacyclin >> prostaglandin (PG) E2 > PGF 2 alpha = PGD2 = U46619.
      Northern blot analysis showed that IP mRNA was most abundantly expressed in
      kidney, with lesser amounts detected in lung and liver. In summary, we have
      cloned and expressed a cDNA for the human prostanoid IP receptor that is
      functionally coupled to a signaling pathway involving stimulation of
      intracellular cAMP production.

PMID- 7512965
TI  - Functional role of N-glycosylation in alpha 5 beta 1 integrin receptor. De-N
      glycosylation induces dissociation or altered association of alpha 5 and beta 1
      subunits and concomitant loss of fibronectin binding activity.
AB  - Fibronectin (FN)-mediated cell adhesion is controlled mainly by alpha 5 beta 1
      (recognizing the RGD sequence) and alpha 4 beta 1 (recognizing the CS-1 peptide
      sequence of FN) integrin receptors. Integrin-dependent cell adhesion to FN is
      greatly promoted by optimal GM3 concentration at the surface membrane (Zheng, M.,
      Fang, H., Tsuruoka, T., Tsuji, T., Sasaki, T., and Hakomori, S. (1993) J. Biol.
      Chem. 268, 2217-2222), and cell adhesion mediated by alpha 4 beta 1 (to FN) or
      alpha 6 beta 1 (to laminin) is inhibited by modifying N-glycosylation processing
      of the integrin receptor (e.g. Akiyama, S. K., Yamada, S. S., and Yamada, K. M.
      (1989) J. Biol. Chem. 264, 18011-18018). We therefore studied the specific role
      of N-glycosylation in alpha 5 beta 1 function. Key findings of the present study
      were as follows. (i) Adhesion of K562 cells to FN-coated plates, which is
      mediated solely by alpha 5 beta 1, was inhibited when cells were treated with a
      mixture of endo-N-acetylglucosaminidase F and peptide -N4-(N
      acetylglucosaminyl)asparagine amidase F (endo-F/PNGase-F). (ii) The alpha 5 beta
      1 receptor at the K562 cell surface tended to dissociate into alpha 5 and beta 1
      subunits when an extract of cells treated with endo-F/PNGase-F was precipitated
      by integrin subunit-specific antibodies, i.e. the alpha 5 subunit was
      preferentially precipitated by anti-alpha 5 monoclonal antibody ZH5, and the beta
      1 subunit was preferentially precipitated by anti-beta 1 monoclonal antibody ZH1.
      When intact cells were extracted and treated with either ZH5 or ZH1, both alpha 5
      and beta 1 were coprecipitated, indicating that the two subunits are normally
      tightly associated with each other. (iii) Adhesion of alpha 5 beta 1-containing
      liposomes (phosphatidylcholine:cholesterol liposomes incorporating purified alpha
      5 beta 1) to FN-coated plates was abolished by treatment of liposomes with endo
      F/PNGase-F. Liposomes incorporating alpha 5 beta 1 pretreated with endo-F/PNGase
      F also did not bind to FN. When purified alpha 5 beta 1 receptor was treated with
      endo-F/PNGase-F followed by ZH5 or ZH1, the alpha 5 or beta 1 subunit was
      precipitated separately, respectively. In contrast, both subunits were always
      coprecipitated when intact purified alpha 5 beta 1 receptor was directly treated
      with ZH5 or ZH1. These findings indicate that N-glycosylation of both the alpha
      and beta subunits of the alpha 5 beta 1 integrin receptor is essential for
      association of these subunits and for optimal binding to FN.

PMID- 7512966
TI  - Human leukemia K562 cell mutant (K562/OA200) selected for resistance to okadaic
      acid (protein phosphatase inhibitor) lacks protein kinase C-epsilon, exhibits
      multidrug resistance phenotype, and expresses drug pump P-glycoprotein.
AB  - A human leukemia K562 cell mutant (K562/OA200) selected for resistance to okadaic
      acid (OA), an inhibitor of protein phosphatases 1 and 2A (PP1/PP2A), has been
      established. In wild type cells, the cytotoxicity of OA was associated with
      mitotic arrest and concentration- and time-dependent DNA fragmentation, a
      hallmark of apoptosis. The mutant was 100-fold more resistant to OA in terms of
      effects on these parameters. Although the synthesis of several proteins was
      altered, enzyme assay and immunoblot analysis indicated that the levels of PP1
      and PP2A were unchanged in the mutant. Protein kinase C (PKC) assays and
      immunoblot analysis of calcium-dependent (cPKC) and calcium-independent (nPKC)
      isoforms revealed that nPKC-epsilon was strikingly absent in the mutant, which
      otherwise expressed in comparable amounts all other isotypes (cPKC-alpha, cPKC
      beta, and nPKC-zeta) also present in the wild type. Northern blot analysis
      confirmed an absence of PKC-epsilon mRNA in the mutant cells. The OA200 cells
      were cross-resistant not only to another PP1/PP2A inhibitor, calyculin A, but
      also to structurally unrelated anticancer drugs (such as vinblastine and taxol)
      and furthermore, overexpressed the verapamil-sensitive drug pump P-glycoprotein
      at both the protein and mRNA levels. The mutant, however, was not cross-resistant
      to several PKC inhibitors tested including cardiotoxin, mastoparan,
      staurosporine, and an alkylphospholipid. Cardiotoxin, at a subtoxic
      concentration, enhanced by 6-fold vinblastine cytotoxicity in OA200 cells. These
      findings indicate that the multidrug resistance phenotype can be induced by
      cytotoxic agents other than conventional anticancer drugs, show that the
      development of multidrug resistance is not necessarily associated with increased
      cPKC activity, and identify certain PKC inhibitors that have potential as
      resistance modulators.

PMID- 7512967
TI  - O-glycosylation in hinge region of mouse immunoglobulin G2b.
AB  - Mouse monoclonal immunoglobulin G2b (IgG2b) antibodies are known to contain two
      forms of the heavy chain that are different in susceptibility to the protease
      attack. In the present study, by use of an affinity column containing sialic acid
      binding lectins from Maackia amurensis seeds, a mouse monoclonal IgG2b was
      successfully separated into three phenotypes, which are different in the degree
      of sialylation in the heavy chain. In the N-linked oligosaccharides from all of
      the IgG2b phenotypes, virtually no sialylation was detected. Elution profiles of
      the lysyl endopeptidase digestion products were compared for the three
      phenotypes. The peptides eluted at different retention times were subjected to
      fast atom bombardment-mass spectrometry and amino acid sequence analyses. It was
      revealed that approximately 40% of the heavy chain of the mouse IgG2b are O
      glycosylated at Thr-221A in the hinge region, predominantly with a
      tetrasaccharide composed of GalNAc, Gal, and two N-glycolylneuraminic acid
      residues. We suggest that the O-glycosylation renders the hinge region resistant
      against the proteolyses of the heavy chain. A therapeutic significance of the O
      glycosylation of IgG2b is briefly discussed.

PMID- 7512968
TI  - Cellular expression of a cloned, hydrophilic, murine acetylcholinesterase.
      Evidence of palmitoylated membrane-bound forms.
AB  - The expression and cellular targeting of murine acetylcholinesterase (AChE) was
      examined after transient transfection of a human 293 cell line with a cDNA
      encoding the hydrophilic T-subunit. Expression of the recombinant clone produced
      catalytically active AChE either bound to the cell membranes, in an intracellular
      pool, or secreted into the medium. About 22% of the cell-associated AChE was
      membrane-linked as dimers and tetramers, required Triton X-100 for extraction,
      and bound to Triton X-100 as assessed by sucrose gradients. Immunocytochemical
      staining of live and permeabilized cells showed reactive epitopes at the plasma
      membrane. Assays of cell surface AChE activity indicated about 18% of the
      cellular enzyme was oriented on the external surface of the plasma membrane.
      Isotopic labeling of cultures with precursors of fatty acylation showed
      incorporation of [3H]palmitate into the membrane-bound fraction of AChE only. The
      label was sensitive to cleavage by mild alkaline methanol treatment, and the
      cleaved lipid was identified as methyl palmitate by thin layer chromatography,
      indicating covalent linkage of the fatty acid through an ester or thioester
      residue. Thus the membrane-bound AChE is palmitoylated, suggesting that fatty
      acylation may serve as an alternative mechanism for anchoring the hydrophilic
      polypeptide subunit of AChE to the external face of the plasma membrane.

PMID- 7512970
TI  - Membrane proximal cleavage of L-selectin: identification of the cleavage site and
      a 6-kD transmembrane peptide fragment of L-selectin.
AB  - Rapid downregulation of L-selectin expression occurs in response to leukocyte
      activation, and it has been speculated to be an integral process in the adhesion
      cascade leading to neutrophil recruitment to sites of inflammation. It has
      previously been proposed that L-selectin is proteolytically cleaved from the cell
      surface; however, the nature of the cleavage site has been unknown. We have
      produced polyclonal antisera against the extracellular domain and against the
      cytoplasmic domain of L-selectin. Both antisera immunoprecipitate the intact form
      of L-selectin from metabolically labeled phytohemagglutinin-stimulated
      lymphoblasts and peripheral blood neutrophils. In addition, the anti-cytoplasmic
      domain serum, but not the antiectodomain serum, immunoprecipitate a 6-kD species
      from PMA activated lymphoblasts and formylmethionylleucylphenylalanine-activated
      neutrophils. Conversely, the antiectodomain serum but not the anti-cytoplasmic
      domain serum immunoprecipitate a 68-kD soluble form of L-selectin from the
      supernatant of PMA-activated lymphoblasts. The appearance of the 6-kD species on
      activated cells correlated with the disappearance of the intact form of L
      selectin and the appearance of the soluble form of L-selectin. A third polyclonal
      serum generated against the membrane proximal region of the ectodomain also
      reacted with the 6-kD species, indicating that this is a transmembrane peptide of
      L-selectin. That the 6-kD species is derived from L-selectin was confirmed by
      immunoprecipitation of the 6-kD species from L-selectin transfectants but not
      from mock transfectants. Radiochemical sequence analysis defined a cleavage site
      between Lys321 and Ser322, which would predict a transmembrane fragment
      consistent in size with the observed 6-kD fragment. A Ser-Phe-Ser motif adjacent
      to the cleavage site is conserved between human, mouse, and rat L-selectin, and a
      related motif is found proximal to transmembrane domains of other downregulated
      proteins, such as ACE, CD16-II, and TNF-RII, suggesting the possibility of a
      common recognition motif.

PMID- 7512972
TI  - The distribution of tenascin-X is distinct and often reciprocal to that of
      tenascin-C.
AB  - We have isolated a cDNA encoding mouse tenascin-X (TN-X), a new member of the
      family of tenascin genes. The TN-X gene lies in the major histocompatibility
      complex (MHC) class III region, as it is the case for its human counterpart. On
      Northern blots we detected a TN-X mRNA of approximately 13 kb in most tissues
      analyzed, whereas in various mouse cell lines mRNAs of approximately 11 and 13 kb
      were detected, suggesting the possibility of alternative splicing of TN-X
      transcripts. We raised antibodies against mouse TN-X fragments expressed in
      bacteria and used these antibodies to identify the TN-X protein in heart cell
      extracts and in the conditioned medium of a renal carcinoma cell line. The
      subunit molecular size of TN-X is approximately 500 kD, suggesting that the
      protein may contain up to 40 fibronectin type III repeats, making it the largest
      tenascin family member known yet. TN-X in conditioned medium, as well as the
      purified protein bind to heparin, but no binding to tenascin-C (TN-C),
      fibronectin, laminin or collagens could be detected. Thus the heparin-binding
      activity may be a common feature of the tenascins. The TN-X mRNA as well as the
      protein are predominantly expressed in heart and skeletal muscle, but the mRNA is
      found in most tissues at a low level. Immunostaining showed the protein to be
      associated with the extracellular matrix of the muscle tissues and with blood
      vessels in all of the tissues analyzed. Although the TN-X gene lies in the MHC
      class III locus, it is not expressed in the lymphoid organs analyzed, except for
      the staining around blood vessels. In skin and tissues of the digestive tract
      often a reciprocal distribution of TN-X and TN-C was observed.

PMID- 7512975
TI  - Retinoic acid enhances adhesiveness, laminin and integrin beta 1 synthesis, and
      retinoic acid receptor expression in F9 teratocarcinoma cells.
AB  - The teratocarcinoma-derived F9 cells respond to retinoic acid (RA) and RA plus
      dibutyrylcyclic adenosine monophosphate (dcAMP) by differentiating into endoderm
      cells, which elaborate a laminin and type IV collagen-rich matrix. We found that
      the induction of differentiation is accompanied by a small but consistent
      increase in cell adhesiveness to a variety of substrates, including laminin.
      Therefore we investigated biochemical mechanisms involved in this phenomenon.
      Endoglycosidase treatment showed that laminin contains complex and hybrid
      oligosaccharide structures. RA enhanced general biosynthesis of laminin without a
      specific increase in galactose incorporation: this sugar was mainly in
      polylactosamine structures in the A chain of laminin and as terminal galactose
      alpha 1,3 galactose in the B chain. Laminin receptor analysis showed that RA
      decreased laminin binding protein-37 (LBP-37) but increased the amount of beta 1
      integrin, suggesting the involvement of beta 1 integrin in the attachment
      process. Northern blot analysis showed increased expression of retinoid receptors
      within hours of RA exposure. These studies demonstrate that RA increases cell to
      substrate interactions by increasing the biosynthesis of laminin and beta 1
      integrin. These effects are most likely subsequent to the RA-induced biosynthesis
      of the retinoid receptors.

PMID- 7512974
TI  - IL-1 alpha and TNF alpha act synergistically to stimulate production of myeloid
      colony-stimulating factors by cultured human bone marrow stromal cells and cloned
      stromal cell strains.
AB  - Human bone marrow stromal cells respond to stimulation by the monokines IL-1 and
      TNF by producing colony-stimulating factors such as GM-CSF and G-CSF. In this
      study we show that IL-1 alpha and TNF alpha act synergistically to stimulate GM
      CSF and G-CSF production by cultured marrow stromal cells. We further show that
      IL-1 alpha and TNF alpha synergistically stimulate production of GM-CSF and G-CSF
      by a clonal stroma-derived cell strain. Although IL-1 and TNF share many of the
      same biological activities, we show that IL-1 alpha and TNF alpha have an unequal
      ability to induce myeloid-CSF production by both cultures, with IL-1 alpha being
      the more potent inducer. We found that induction by IL-1 alpha and TNF alpha was
      independent of cell proliferation. The effect of IL-1 alpha and TNF alpha on
      production of the two myeloid-CSFs by the clonal cells was significantly greater
      than the unfractionated passaged stromal cultures, having the greater effect on G
      CSF production. The clonally derived stromal cells constitutively produced colony
      stimulating activity, in particular GM-CSF, at levels easily detected by ELISA.
      These findings show that, in addition to the overlapping and additive activities
      of IL-1 alpha and TNF alpha, they can interact synergistically. Our findings
      further suggest that a small subpopulation of stroma cells may be the major
      producer of G-CSF in the marrow microenvironment during immune response.

PMID- 7512976
TI  - Staurosporine, a non-specific PKC inhibitor, induces keratinocyte differentiation
      and raises intracellular calcium, but Ro31-8220, a specific inhibitor, does not.
AB  - The responsiveness of normal human keratinocytes to different modulators of
      protein kinase C (PKC) was investigated. The PKC agonist TPA, staurosporine (a
      non-specific inhibitor), and Ro31-8220 (a specific inhibitor) were studied for
      effect on cell morphology, growth rate, involucrin expression, and intracellular
      calcium levels. Surprisingly the response to nanomolar concentrations of
      staurosporine was similar to TPA and induced a fusiform morphology, inhibited
      growth, increased involucrin levels, and raised intracellular calcium.
      Staurosporine also increased the number of cornified envelopes, and its action
      therefore appeared identical to TPA. In contrast, Ro31-8220 had little effect on
      morphology or growth and blocked both the TPA-induced growth inhibition and
      calcium rise. Ro31-8220 had no effect on staurosporine-induced growth inhibition
      but partially reduced its associated calcium rise. These results suggest PKC
      activation is required for keratinocyte differentiation and that staurosporine
      acts like a PKC agonist to give a similar effect as TPA. Specific inhibition of
      PKC by Ro31-8220 inhibits TPA-induced differentiation.

PMID- 7512971
TI  - Monospecific and common glycoprotein ligands for E- and P-selectin on myeloid
      cells.
AB  - E- and P-selectin are inducible cell adhesion molecules on endothelial cells,
      which function as Ca(2+)-dependent lectins and mediate the binding of neutrophils
      and monocytes. We have recently identified a 150-kD glycoprotein ligand for E
      selectin on mouse myeloid cells, using a recombinant antibody-like form of mouse
      E-selectin. Here, we report that this ligand does not bind to an analogous P
      selectin fusion protein. Instead, the chimeric P-selectin-IgG protein recognizes
      a 160-kD glycoprotein on the mouse neutrophil progenitor 32D cl 3, on mature
      mouse neutrophils and on human HL60 cells. The binding is Ca(2+)-dependent and
      requires the presence of sialic acid on the ligand. This P-selectin-ligand is not
      recognized by E-selectin. Removal of N-linked carbohydrate side chains from the
      150-kD and the 160-kD monospecific selectin ligands abolishes the binding of both
      ligands to the respective selectin. Treatment of HL60 cells with Peptide: N
      glycosidase F inhibited cell binding to P- and E-selectin. In addition,
      glycoproteins of 230 and 130 kD were found on mature mouse neutrophils, which
      bound both to E- and P-selectin in a Ca(2+)-dependent fashion. The signals
      detected for these ligands were 15-20-fold weaker than those for the monospecific
      ligands. Both proteins were heavily sialylated and selectin-binding was blocked
      by removal of sialic acid, but not by removal of N-linked carbohydrates. Our data
      reveal that E- and P-selectin recognize two categories of glycoprotein ligands:
      one type requires N-linked carbohydrates for binding and is monospecific for each
      of the two selectins and the other type binds independent of N-linked
      carbohydrates and is common for both endothelial selectins.

PMID- 7512977
TI  - [Non-Hodgkin's malignant lymphoma of the cervix uteri].

PMID- 7512973
TI  - BEHAB, a new member of the proteoglycan tandem repeat family of hyaluronan
      binding proteins that is restricted to the brain.
AB  - Hyaluronan (HA) is a ubiquitous component of the extracellular matrix of all
      tissues. In the mammalian central nervous system (CNS) HA is present throughout
      development and into adulthood. While the functions of HA are likely to be
      mediated by HA-binding proteins, no cell or tissue specific HA-binding proteins
      have been reported. In an effort to characterize the composition of the
      extracellular matrix of the CNS, we sought to identify neural HA-binding
      proteins. We report here the isolation and characterization of a cDNA with a high
      degree of sequence homology to members of the proteoglycan tandem repeat (PTR)
      family of HA-binding proteins. Unlike other HA-binding proteins, the expression
      of this cDNA is restricted to the CNS. We propose the name BEHAB, Brain Enriched
      HyAluronan Binding protein, for this gene. The expression of BEHAB mRNA is
      developmentally regulated; expression is first detected in the late embryonic
      period and peaks during the first two postnatal weeks. In the embryo, BEHAB is
      expressed at highest levels in mitotically active cells. The sequence of BEHAB
      has long stretches of identity between rat and cat, suggesting that the encoded
      protein is functionally important. The size and sequence of BEHAB are consistent
      with the possibility that it could serve a function like link protein,
      stabilizing interactions between HA and brain proteoglycans. These observations
      suggest that existence of other tissue specific HA-binding proteins.

PMID- 7512978
TI  - What is the role of early detection and screening in cancer control?
AB  - The guidelines for early cancer detection of the American Cancer Society are
      critically reviewed. It is concluded that only for some elements of the
      guidelines relating to breast, cervix and colorectal cancer is there good
      evidence of effectiveness sufficient for public health policy. However, for
      breast cancer screening under the age of 50, and prostate cancer screening at any
      age, the evidence currently does not justify the approaches recommended by the
      Society.

PMID- 7512969
TI  - Contrasting roles for integrin beta 1 and beta 5 cytoplasmic domains in
      subcellular localization, cell proliferation, and cell migration.
AB  - To carry out a detailed comparison of the roles of integrin beta 1 and beta 5
      cytoplasmic domains, we expressed both wild type beta 1 and chimeric beta 1/5
      constructs in CHO cells. In the latter, the cytoplasmic domain of beta 1 was
      replaced with that of beta 5. The human beta 1 and beta 1/5 constructs appeared
      at similar levels at the cell surface (mostly as alpha 5 beta 1 heterodimers) and
      contributed equally to CHO cell adhesion to fibronectin. However, beta 1 but not
      beta 1/5 localized to focal adhesion-like structures when CHO cells were spread
      on fibronectin. Furthermore, only the beta 1-CHO cells showed increased
      proliferation in response to fibronectin plus an integrin-activating anti-beta 1
      antibody, and showed increased appearance of 32P-labeled protein (p90) that
      correlated with proliferation. In sharp contrast, the beta 1/5-CHO cells were
      notably more migratory than beta 1-CHO cells in a transwell haptotactic migration
      assay. These results indicate that the beta 1 and beta 5 integrin subunit
      cytoplasmic domains can translate similar adhesive information into highly
      contrasting subsequent events. Thus, we have established that "inside-out" and
      "outside-in" integrin signaling pathways are regulated by fundamentally distinct
      mechanisms. In addition, we suggest that the same properties of the beta 1
      cytoplasmic domain that promote recruitment to visible focal adhesion-like
      structures may also be conductive to cell proliferation. Conversely, the
      properties of the beta 5 tail that make it less likely to localize into focal
      adhesion-like structures may contribute to enhanced cell migration.

PMID- 7512979
TI  - Specific tolerance to an acetylcholine receptor epitope induced in vitro in
      myasthenia gravis CD4+ lymphocytes by soluble major histocompatibility complex
      class II-peptide complexes.
AB  - In autoimmune disorders, inactivation of pathogenic antigen-specific T cells,
      rather than global immunosuppression, would be highly desirable. One way to
      achieve this would be to deliver the first antigen-specific signal to the T cell
      in the absence of the second costimulatory signal. Myasthenia gravis (MG) is a
      well-characterized autoimmune disease in which T cell-dependent autoantibodies
      are directed against the acetylcholine receptor (A ChR) at the neuromuscular
      junction. AChR-specific T cells have been cloned from MG patients, and in this
      study, we have induced long-lasting tolerance in vitro in one particular clone
      (PM-A1) with a known peptide epitope (alpha 144-163) and MHC class II restriction
      (DR4 Dw14.2 or 4.2) by using soluble MHC-class II peptide complexes.
      Preincubation of PM-A1 T cells with such complexes induced death by apoptosis in
      < or = 40-50% of the AChR-specific cells. Surviving cells remained refractory to
      stimulation with AChR-derived synthetic peptides or recombinant polypeptides for
      < or = 38 d after complex treatment. These effects were highly specific, dose
      dependent and required > 2 h preincubation. The T cells could be protected from
      the tolerizing effects of complex by coincubation with DR-matched or -mismatched
      antigen-presenting cells. This work shows that antigen-specific T cells can be
      selectively killed or anergized using soluble MHC class II: peptide complexes.
      Such an antigen-specific therapy offers a rational approach to the immunotherapy
      of autoimmune or allergic disease in vivo.

PMID- 7512980
TI  - Bronchial biopsy evidence for leukocyte infiltration and upregulation of
      leukocyte-endothelial cell adhesion molecules 6 hours after local allergen
      challenge of sensitized asthmatic airways.
AB  - We have examined the mucosal changes occurring in bronchial biopsies from six
      atopic asthmatics 5-6 h after local endobronchial allergen challenge and compared
      them with biopsies from saline-challenged segments from the same subjects at the
      same time point. All the subjects developed localized bronchoconstriction in the
      allergen-challenged segment and had a decrease in forced expiratory volume in 1 s
      (FEV1) (P < 0.01) and a decrease in their methacholine provocative concentration
      of agonist required to reduce FEV1 from baseline by 20% (P < 0.05) 24 h
      postchallenge. At 6 h we observed an increase in neutrophils (P = 0.03),
      eosinophils (P = 0.025), mast cells (P = 0.03), and CD3+ lymphocytes (P = 0.025),
      but not in CD4+ or CD8+ lymphocyte counts. We also detected an increase in
      endothelial intercellular adhesion molecule type 1 (P < 0.05) and E-selectin (P <
      0.005), but not vascular cell adhesion molecule type 1 expression with a
      correlative increase in submucosal and epithelial LFA+ leucocytes (P < 0.01).
      Thus, in sensitized asthmatics, local endobronchial allergen instillation leads
      to an increased inflammatory cell infiltrate of the airway mucosa that involves
      upregulation of specific adhesion molecules expressed on the microvasculature.

PMID- 7512981
TI  - Similar levels of mRNA from the W1282X and the delta F508 cystic fibrosis
      alleles, in nasal epithelial cells.
AB  - The effect of nonsense mutations on mRNA levels is variable. The levels of some
      mRNAs are not affected and truncated proteins are produced, while the levels of
      others are severely decreased and null phenotypes are observed. The effect on
      mRNA levels is important for the understanding of phenotype-genotype association.
      Cystic fibrosis (CF) is a lethal autosomal recessive disease with variable
      clinical presentation. Recently, two CF patients with mild pulmonary disease
      carrying nonsense mutations (R553X, W1316X) were found to have severe deficiency
      of mRNA. In the Jewish Ashkenazi CF patient population, 60% of the chromosomes
      carry a nonsense mutation, W1282X. Patients homozygous for this mutation have
      severe disease presentation with variable pulmonary disease. The presence of CF
      transcripts in a group of patients homozygous and heterozygous for this mutation
      was studied by reverse transcriptase PCR of various regions of the gene.
      Subsequent hybridization to specific CF PCR probes and densitometry analysis
      indicated that the CF mRNA levels in patients homozygous for the W1282X mutation
      are not significantly decreased by the mutation. mRNA levels were compared for
      patients heterozygous for the W1282X mutation. The relative levels of mRNA with
      the W1282X, and the delta F508 or the normal alleles, were similar in each
      patient. These results indicate that the severe clinical phenotype of patients
      carrying the W1282X mutation is not due to a severe deficiency of mRNA. In
      addition, the severity, progression, and variability of the pulmonary disease are
      affected by other, as yet unknown factors.

PMID- 7512982
TI  - Role of H1 receptors and P-selectin in histamine-induced leukocyte rolling and
      adhesion in postcapillary venules.
AB  - The objective of this study was to define the nature, magnitude, and mechanisms
      of histamine-induced leukocyte-endothelial cell interactions in postcapillary
      venules of the rat mesentery using intravital microscopic techniques. Superfusion
      of the mesentery with histamine (10(-7)-10(-5) M) resulted in a dose-related
      increase in the number of rolling leukocytes, a reduction in rolling velocity,
      and an increased clearance of FITC-labeled rat albumin from blood to superfusate.
      The histamine-induced recruitment of rolling leukocytes and increased albumin
      clearance were prevented by histamine H1 (hydroxyzine, diphenhydramine) but not
      H2 (cimetidine) receptor antagonists. Because histamine induces expression of the
      adhesion molecule P-selectin in cultured endothelial cells, a monoclonal antibody
      directed against rat P-selectin and soluble sialyl-LewisX oligosaccharide (the
      carbohydrate ligand to P-selectin) were also tested as inhibitors. Both were
      effective in preventing the histamine-induced recruitment of rolling leukocytes,
      but neither agent attenuated the increased albumin clearance. These observations
      suggest that (a) histamine recruits rolling leukocytes and increases albumin
      leakage in postcapillary venules via H1 receptor activation, (b) histamine
      induced recruitment of rolling leukocytes is mediated in part by P-selectin
      expressed on the endothelial cell surface, and (c) the histamine-induced vascular
      albumin leakage is unrelated to leukocyte-endothelial cell adhesion. Our results
      are consistent with the view that histamine may act as a mediator of acute
      inflammatory reactions.

PMID- 7512984
TI  - Recruitment of lymphocytes during cutaneous delayed hypersensitivity in nonhuman
      primates is dependent on E-selectin and vascular cell adhesion molecule 1.
AB  - Previous investigations of cutaneous delayed hypersensitivity (DHR) in humans and
      animals have demonstrated that lymphocyte recruitment from blood is temporally
      and spatially associated with the de novo, asynchronous expression of both
      vascular cell adhesion molecule 1 (VCAM-1) and E-selectin on dermal endothelium.
      In this study, DHR was induced in rhesus monkeys sensitized against tuberculin in
      order to investigate the contribution of E-selectin and VCAM-1 in lymphocyte
      recruitment to skin. Intravenous infusions of neutralizing doses of F(ab')2
      fragments of murine antibodies to either E-selectin or VCAM-1 during the early
      inductive phases of DHR showed that murine IgG localized to dermal endothelium at
      the site of DHR in a pattern kinetically similar to the expression of each
      endothelial adhesion protein. Most importantly, the relative numbers of
      lymphocytes localized to the inflammatory site were significantly reduced in DHR
      modified with infusions of antibodies to either VCAM-1 or E-selectin, while the
      numbers of lymphocytes recruited to skin in the animal given F(ab')2 fragments of
      an irrelevant murine monoclonal antibody of the same isotype and at the same dose
      were not changed. Moreover, in individual animals, the relative inhibition
      achieved with a particular antibody was proportional to the magnitude of
      expression of the targeted adhesion protein. Therefore, both VCAM-1 and E
      selectin are functionally relevant in the genesis of cutaneous DHR, and each
      appears to contribute to lymphocyte recruitment in relation to its relative
      degree of expression in any one particular animal.

PMID- 7512985
TI  - Bacterial lipopolysaccharide primes human neutrophils for enhanced release of
      arachidonic acid and causes phosphorylation of an 85-kD cytosolic phospholipase
      A2.
AB  - Production of leukotriene B4 (LTB4) by human neutrophils (PMN) in response to
      different stimuli is increased after pretreatment with lipopolysaccharides (LPS).
      We have analyzed the steps in arachidonic acid (AA) metabolism affected by LPS by
      examining release of AA and its metabolites from [3H]AA prelabeled PMN.
      Pretreatment of PMN for 60 min with up to 1 microgram/ml of LPS alone had no
      effect, but release of [3H]AA was stimulated up to fivefold during subsequent
      stimulation with a second agent. In the absence of LPS-binding protein (LBP),
      priming was maximal after pretreatment of PMN with 10 ng of LPS/ml for 60 min; in
      the presence of LBP maximal priming occurred within 45 min at 0.1 ng of LPS/ml
      and within 15 min at 100 ng of LPS/ml. Treatment of PMN with 10 ng of LPS/ml also
      increased uptake of opsonized zymosan by up to 60%. Phospholipids are the source
      of released [3H]AA. No release was observed from [14C]oleic acid (OA)-labeled PMN
      suggesting that phospholipolysis may be specific for [3H]AA-labeled phospholipid
      pools. Cytosol from PMN primed with LPS contains two to three times the
      phospholipase A2 (PLA2) activity of control PMN, against 1-palmitoyl-[2
      14C]arachidonoyl-phosphatidylcholine. This activity is Ca2+ dependent and
      dithiothreitol resistant. LPS priming is accompanied by reduced migration during
      SDS-PAGE of an 85-kD protein, identified as a cytosolic PLA2. The extent and
      kinetics of this effect of LPS on cPLA2 parallel the priming of [3H]AA release,
      both depending on LPS concentration either with or without LBP. These findings
      suggest that priming by LPS of AA metabolism by PMN includes phosphorylation of
      an AA-phospholipid-selective cytosolic PLA2 that is dissociated from activation
      until a second stimulus is applied.

PMID- 7512983
TI  - Genetic mutations in the K1 and K10 genes of patients with epidermolytic
      hyperkeratosis. Correlation between location and disease severity.
AB  - Epidermolytic hyperkeratosis (EH) is a skin disease caused by mutations in the
      genes encoding K1 and K10, the differentiation-specific keratins of epidermis. To
      explore the heterogeneity of mutations and to assess whether a correlation exists
      between disease severity and the extent to which a mutation interferes with
      keratin network formation, we determined the genetic bases of four severe
      incidences of EH and one unusually mild case. Two severe cases have the same
      mutation, K10-R156:C, at a conserved arginine that we previously showed was
      mutated to a histidine in two unrelated EH families. An additional severe case
      has a mutation six residues away, still within the amino end of the alpha-helical
      rod domain of K10. The other severe case has a mutation in the conserved carboxy
      end of the K1 rod. In contrast, affected members of the atypically mild family
      have a mutation just proximal to the conserved carboxy end of the K10 rod. By
      genetic engineering and gene transfection, we demonstrate that each mutation is
      functionally responsible for the keratin filament aberrations that are typical of
      keratinocytes cultured from these patients. Moreover, we show that the mild EH
      mutation less severely affects filament network formation. Taken together, our
      studies strengthen the link between filament perturbations, cell fragility, and
      degeneration.

PMID- 7512987
TI  - Mast cell degranulation induced by type 1 fimbriated Escherichia coli in mice.
AB  - The strategic location of mast cells at the host-environment interface and their
      ability to release potent mediators of inflammation have suggested that these
      cells may play a pivotal role in host defense against bacterial infection. The
      ability of the opportunistic pathogen, Escherichia coli, to induce degranulation
      of mast cells obtained from the mouse peritoneum was investigated. We determined
      that unlike a mutant derivative deficient in the FimH subunit of the fimbriae or
      nonfimbriated E. coli, type 1 fimbriated E. coli induced mast cell degranulation
      in vitro. The magnitude of mast cell degranulation was directly proportional to
      the number of adherent bacteria on the cell surface in the initial period of the
      interaction. Using a mouse model of bacterial peritonitis, we demonstrated mast
      cell degranulation and histamine release by type 1 fimbriated bacteria in vivo.
      Furthermore, beads coated with FimH but not with FimA, the major subunit of type
      1 fimbriae, evoked mast cell release of histamine in vivo in amounts comparable
      to that elicited by type 1 fimbriated E. coli. These studies reveal that mast
      cells can be degranulated by interaction with type 1 fimbriated E. coli and that
      FimH, the mannose-binding component of the fimbriae, is a potent mast cell
      stimulant.

PMID- 7512989
TI  - Treatment with oral clotrimazole blocks Ca(2+)-activated K+ transport and
      reverses erythrocyte dehydration in transgenic SAD mice. A model for therapy of
      sickle cell disease.
AB  - Prevention of red cell K+ and water loss is a therapeutic strategy for sickle
      cell disease. We have investigated in vitro and in vivo the effects of
      clotrimazole (CLT) and miconazole (MIC) on transgenic mice red cells expressing
      hemoglobin SAD. CLT blocked the Gardos channel (ID50 75 +/- 22 nM; n = 3) and the
      A23187-induced dehydration of Hbbs/Hbbthal SAD 1 mouse erythrocytes in vitro.
      Oral treatment with CLT (160 mg/kg per d) and MIC (100 mg/kg per d) inhibited the
      Gardos channel in both SAD 1 and control (Hbbs/Hbbthal) mice. In the SAD 1 mice
      only, cell K+ content increased, and mean corpuscular hemoglobin concentration
      and cell density decreased. After 7 d of treatment, the hematocrit of SAD 1, CLT
      treated animals also increased. All changes were fully reversible. Long-term
      treatments of SAD 1 mice with oral CLT (80 mg/kg per d for 28 d) lead to
      sustained increases in cell K+ content and hematocrit and sustained decreases in
      mean corpuscular hemoglobin concentration and cell density, with no changes in
      animals treated with vehicle alone. Thus, CLT and MIC can reverse dehydration and
      K+ loss of SAD 1 mouse erythrocytes in vitro and in vivo, further supporting the
      potential utility of these drugs in the treatment of sickle cell anemia.

PMID- 7512986
TI  - Molecular composition of Ro small ribonucleoprotein complexes in human cells.
      Intracellular localization of the 60- and 52-kD proteins.
AB  - Ro small ribonucleoprotein complexes (RoRNPs) are thought to comprise several
      proteins, including the 60-kD Ro and the 52-kD Ro proteins, and several small
      RNAs, designated Y RNAs. Although RoRNPs are fairly ubiquitous in nature, their
      precise composition remains unknown, their function has been elusive, and their
      intracellular localization has been controversial. We have analyzed HeLa cell
      extracts by glycerol density gradient fractionation in order to determine the
      distribution of the individual protein and RNA components of RoRNPs. We found
      that 52-kD Ro was not detectable in an RNP complex with the 60-kD protein under a
      variety of conditions. Pretreatment of cell extracts with ribonuclease affected
      gradient migration of the 60-kD but not the 52-kD protein, suggesting that the
      latter is not complexed with RNA. The migration of the hY RNAs in these gradients
      closely followed that of 60-kD and not 52-kD Ro. Immunofluorescence analysis of
      two different cell lines with monospecific antibodies against 52- and 60-kD
      proteins strongly suggests that these two proteins are not present on overlapping
      sets of structures in vivo. We conclude that the 52-kD Ro protein is not a
      detectable component of the RoRNP complex under these conditions despite its
      reactivity with Ro autoimmune antisera.

PMID- 7512990
TI  - The pathogenesis of adoptive murine autoimmune diabetes requires an interaction
      between alpha 4-integrins and vascular cell adhesion molecule-1.
AB  - An adoptive transfer model of insulin-dependent diabetes mellitus (IDDM) in the
      nonobese diabetic mouse was used to examine the roles of alpha 4-integrin,
      vascular cell adhesion molecule 1 (VCAM-1); and intercellular adhesion molecule 1
      (ICAM-1) in the pathogenesis of autoimmune diabetes. Antibodies specific for both
      alpha 4-integrin and one of its ligands, VCAM-1, were able to delay onset of
      diabetes and decrease the incidence of the disease in adoptive transfer studies.
      This blocking of disease was accompanied by a marked decrease in lymphocytic
      infiltration of the islets of Langerhans. Furthermore, these antibodies
      preferentially block entrance of CD4 T cells into the tissue. Antibodies specific
      for ICAM-1 had little effect on the onset or incidence of IDDM. Thus, we conclude
      that an alpha 4-integrin-VCAM-1 interaction is important in T cell entry into the
      islets of Langerhans and in the pathogenesis of IDDM. In addition, the cascade of
      events leading to T cell transit across endothelium may be different for CD4 and
      CD8 cells, and may differ depending on the endothelium involved. Our results
      support the more general conclusion that an alpha 4-integrin-VCAM-1 interaction
      may be crucial in allowing activated effector CD4T cells to leave the blood and
      enter tissue to clear infection.

PMID- 7512988
TI  - Functional switching of macrophage responses to tumor necrosis factor-alpha (TNF
      alpha) by interferons. Implications for the pleiotropic activities of TNF alpha.
AB  - Recent work conducted in our laboratory has been directed towards understanding
      the role of TNF alpha in stimulating the synthesis of two macrophage gene
      products, namely IGF-1, a growth factor implicated in wound repair and fibrosis,
      and complement component factor B (Bf), an alternative pathway complement
      component. The expression of these proteins is induced by hyaluronic acid and
      poly (I:C), respectively, although TNF alpha plays a requisite role in the
      expression of both proteins. The objective of this study was to determine the
      mechanism governing the dichotomy in the expression of IGF-1 and Bf by TNF alpha.
      First, we questioned if the diversity in IGF-1 and Bf synthesis was regulated at
      the level of TNF receptor usage. Second, based on earlier findings that IFNs
      contribute to the initiation of Bf expression, we determined if IFNs modulate the
      response of macrophages to TNF alpha. Our data show that differences in TNF
      receptor usage cannot fully explain the dichotomy in the expression of IGF-1 and
      Bf. However, prior exposure to IFN-beta or IFN-gamma was found to be a dominant
      factor controlling the expression of these proteins, suppressing IGF-1, and
      enhancing Bf. These findings indicate that IFNs mediate a functional "switch" in
      the response of macrophages to TNF alpha and suggest that the pattern of cytokine
      expression by diverse macrophage stimuli is an important determinant of the
      eventual responses of macrophages to TNF alpha.

PMID- 7512991
TI  - Elevated expression of type VII collagen in the skin of patients with systemic
      sclerosis. Regulation by transforming growth factor-beta.
AB  - A hallmark of systemic sclerosis (SSc) is the development of tissue fibrosis.
      Excessive production of several connective tissue components normally present in
      the dermis, including type I, III, V, and VI collagens as well as fibronectin and
      proteoglycans, is a consistent finding in the skin of SSc patients. Type VII
      collagen is a major constituent of anchoring fibrils, present in the skin at the
      dermal-epidermal basement membrane zone. TGF-beta has been shown to upregulate
      the expression of the type VII collagen gene. In this study, we assessed the
      expression of type VII collagen and TGF-beta in the skin of patients with SSc.
      Indirect immunofluorescence showed an abundance of type VII collagen in the
      patients' skin, including the dermis. Ultrastructural analysis of SSc skin
      revealed an abundance of fibrillar material, possibly representing type VII
      collagen. The increased expression of type VII collagen epitopes was accompanied
      by the elevated expression of immunodetectable TGF-beta 1 and TGF-beta 2. Dermal
      fibroblasts cultured from the affected individuals showed a statistically
      significant (P < 0.02) increase in the expression of type VII collagen at the
      mRNA level, as detected by reverse transcription-PCR with a mutated cDNA as an
      internal standard, and increased deposition of the protein as assessed by
      indirect immunofluorescence. Thus, type VII collagen is abundantly present in SSc
      patients' dermis, a location not characteristic of its normal distribution, and
      its aberrant expression may relate to the presence of TGF-beta in the same
      topographic distribution. The presence of type VII collagen in the dermis may
      contribute to the tightly bound and indurated appearance of the affected skin in
      SSc patients.

PMID- 7512994
TI  - Development of a PCR probe test for identifying Pseudomonas aeruginosa and
      Pseudomonas (Burkholderia) cepacia.
AB  - AIMS: To develop a system of species specific polymerase chain reaction (PCR) and
      DNA hybridisation based on 16s ribosomal RNA sequences for the identification of
      Pseudomonas aeruginosa and Pseudomonas (Burkholderia) cepacia in sputum from
      children with cystic fibrosis. METHODS: Most of the 16s rRNA sequences from
      strains of Ps aeruginosa, Ps (Burkholderia) cepacia, and Ps putida were
      determined. PCR primers and DNA probes were synthesised from suitable sequences
      and then evaluated on bacterial cultures and sputum samples. RESULTS: About 1000
      bases of sequence was obtained from strains of Ps aeruginosa, Ps (Burkholderia)
      cepacia, and Ps putida. PCR of bacterial cultures was species specific, but PCR
      on sputum resulted in some non-specific amplification products. The subsequent
      hybridisation reaction was species specific. CONCLUSION: A species specific
      system of PCR and DNA hybridisation based on 16s rRNA sequences is applicable in
      clinical practice, and may aid the early diagnosis of respiratory tract infection
      with small numbers of Ps aeruginosa and Ps (Burkholderia) cepacia in patients
      with cystic fibrosis.

PMID- 7512995
TI  - A new monoclonal antibody (3A5) that recognises a fixative resistant epitope on
      tissue macrophages and monocytes.
AB  - AIMS: To develop a monoclonal antibody specific for human macrophages in
      routinely processed material. METHODS: The monoclonal antibody was derived from a
      mouse popliteal lymph node after subcutaneous immunisation in the footpad with
      fragments of human spleen depleted of lymphocytes and erythrocytes. RESULTS: 3A5
      is a monoclonal antibody reactive with macrophages, monocytes, and histiocytes in
      routinely processed (formalin fixed, paraffin wax embedded) human tissue
      specimens. Unlike the well known panmacrophage marker KP1 (CD68), neither
      dendritic cells (interdigitating cells, Langerhans' cells, and microglia) nor
      myeloid, lymphoid, or epithelial cells stained with 3A5. CONCLUSION: As the
      staining pattern of 3A5 is restricted, compared with other macrophage markers and
      the recognised epitope survives common fixation and embedding procedures, 3A5 is
      a valuable marker for histiocytes and macrophages in routine diagnostic
      applications.

PMID- 7512998
TI  - Distribution of primary afferent fibers projecting from hindlimb cutaneous nerves
      to the medulla oblongata in the cat and rat.
AB  - The dorsal column nuclear complex, one of the most important relays for tactile
      perception, has well been known to be somatotopically organized. Topographical
      arrangements of terminal sites of individual cutaneous nerves within the dorsal
      column nuclei, however, have not been examined systematically, although many
      studies have been done upon primary afferents to the medulla oblongata, including
      the dorsal column nuclear complex. Thus, in the present study, distribution of
      primary afferent fibers projecting from the hindlimb cutaneous nerves to the
      medulla oblongata was examined in the cat and rat by means of the transganglionic
      transport method with horseradish peroxidase. Cutaneous primary afferent fibers
      projecting from the hindlimb to the medulla oblongata were distributed mainly in
      the ipsilateral gracile nucleus. Terminal labeling in the gracile nucleus was
      seen at all rostrocaudal levels of the nucleus, occasionally including the
      nuclear part straddling the midline (the median or accessory nucleus). The
      labeled axon terminals in the gracile nucleus were more densely distributed in
      the middle and caudal parts of the nucleus than in the rostral part. Although the
      fields of termination of the hindlimb cutaneous nerves overlapped in the gracile
      nucleus, the foci of the terminal labeling of the nerves innervating the distal
      parts of the hindlimb were located more medially or dorsomedially than those of
      the nerves innervating the proximal parts. Terminal labeling was further found in
      a small zone immediately medial to the rostromedial border of the external
      cuneate nucleus. This hitherto undescribed zone (U zone) contained a small
      cluster of medium-sized neurons in the cat. Although no particular cell cluster
      was found in the U zone of the rat, convergence of the primary afferent fibers of
      the cutaneous nerve from the hindlimb appeared to occur as in the U zone of the
      cat.

PMID- 7512996
TI  - Safer staining method for acid fast bacilli.

PMID- 7512992
TI  - Increased damage to type II collagen in osteoarthritic articular cartilage
      detected by a new immunoassay.
AB  - A new immunoassay was developed to detect denaturation of type II collagen in
      osteoarthritis (OA). A peptide, alpha 1 (II)-CB11B, located in the CB11 peptide
      of type II collagen, was synthesized and used to produce a monoclonal antibody
      (COL2-3/4m) of the IgG1 (kappa) isotype. This reacts with a defined epitope in
      denatured but not native type II collagen and the alpha 3 chain of type XI
      collagen. The latter is present in very small amounts (about 1% wt/wt) in
      cartilage relative to the alpha 1 (II) chain. By using an enzyme-linked
      immunosorbent assay, type II collagen denaturation and total type II collagen
      content were determined. The epitope recognized by the antibody was resistant to
      cleavage by alpha-chymotrypsin and proteinase K which were used to extract alpha
      1 (II)-CB11B from the denatured (alpha-chymotrypsin soluble) and residual native
      (proteinase K soluble) collagen alpha-chains, respectively, present in human
      femoral articular cartilage. Type II collagen content was significantly reduced
      from a mean (range) of 14% (9.2-20.8%) of wet weight in 8 normal cartilages to
      10.3% (7.4-15.0%) in 16 OA cartilages. This decrease, which may result in part
      from an increased hydration, was accompanied by an increase in the percent
      denaturation of type II collagen in OA to 6.0% of total type II collagen compared
      with 1.1% in normal tissue. The percent denaturation was ordinarily greater in
      the more superficial zone than in the deep zone of OA cartilage.

PMID- 7512997
TI  - Effects of inhibition of serotonin synthesis on 5-hydroxyindoleacetic acid
      excretion, in healthy subjects.
AB  - The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite
      of serotonin, reflects the content and turnover of gastrointestinal (GI)
      serotonin. Employing longitudinal measurements of 5-HIAA, the authors
      investigated in healthy subjects (n = 43) how manipulations of serotonin
      synthesis affect GI serotonin. Under conditions of serotonin-free diets, the
      intersubject and intrasubject variability (coefficient of variation) for 5-HIAA
      excretion averaged 33% and 14%, respectively. Dietary tryptophan restrictions to
      50% of minimal daily requirements (which is equivalent to a 10-fold reduction in
      baseline tryptophan intake) decreased by half the urinary excretion of 5-HIAA,
      irrespective of the caloric content of diet. Restoration to the regular
      tryptophan intake produced a rapid normalization of the 5-HIAA excretion. Neutral
      amino acids are known to compete with the intestinal transport absorption
      mechanisms of tryptophan. Administration of neutral amino acids (1.8 g, by mouth,
      three times a day, before each meal) or of carbidopa (50 mg, by mouth, three
      times a day for 3 days) to a normal tryptophan diet failed to alter significantly
      the 5-HIAA excretion. Further, neutral amino acids failed to enhance the
      reduction in 5-HIAA produced by the low-tryptophan diet. The failure of these
      treatments to reduce 5-HIAA excretion could be due to large capacity transport
      and decarboxylation systems for tryptophan. Other possibilities are discussed. In
      summary, dietary tryptophan is essential for the maintenance of GI serotonin.
      Reductions or increases in dietary tryptophan are the easiest and most effective
      method to alter GI serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7512993
TI  - A novel exon in the cystic fibrosis transmembrane conductance regulator gene
      activated by the nonsense mutation E92X in airway epithelial cells of patients
      with cystic fibrosis.
AB  - Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene. We report on a novel nonsense mutation that
      leads to exon skipping and the activation of a cryptic exon. Screening of genomic
      DNA from 700 German patients with CF uncovered four cases with the nonsense
      mutation E92X, a G-->T transversion that creates a termination codon and affects
      the first base of exon 4 of the CFTR gene. Lymphocyte RNA of two CF patients
      heterozygous for E92X was found to contain the wild type sequence and a
      differentially spliced isoform lacking exon 4. In RNA derived from nasal
      epithelial cells of E92X patients, a third fragment of longer size was observed.
      Sequencing revealed the presence of E92X and an additional 183-bp fragment,
      inserted between exons 3 and 4. The 183-bp sequence was mapped to intron 3 of the
      CFTR gene. It is flanked by acceptor and donor splice sites. We conclude that the
      183-bp fragment in intron 3 is a cryptic CFTR exon that can be activated in
      epithelial cells by the presence of the E92X mutation. E92X abolishes correctly
      spliced CFTR mRNA and leads to severe cystic fibrosis.

PMID- 7513002
TI  - Rapid staining with carcinoembryonic antigen aids limited excision of
      extramammary Paget's disease treated by Mohs surgery.
AB  - Extensive extramammary Paget's (EMPD) disease of the perineum in a 68-year-old
      man was treated by Mohs surgery. To facilitate identification of involved tissue
      a rapid staining carcinoembryonic antigen was used. This technique proved a
      useful adjunct to conventional hemotoxylin-eosin (H&E) stains. It was especially
      useful in highlighting involvement in areas of marked dysplasia/artifact where
      discrimination is often difficult. It is recommended that such a technique offers
      considerable benefits over H&E staining when confronted by such tissue
      morphology.

PMID- 7513001
TI  - The lipopolysaccharide of Porphyromonas gingivalis is not antigenically cross
      reactive with that of other species.
AB  - Large numbers of Porphyromonas, Prevotella, and Bacteroides strains were screened
      by 3 monoclonal antibodies (MAbs) and 8 rabbit antisera raised against
      Porphyromonas gingivalis, in order to detect any possible recognition of non-P.
      gingivalis surface antigens by these immunoreagents. All three MAbs, which were
      LPS-specific, extensively recognized LPS from 10 P. gingivalis strains in
      immunoblotting, whereas they recognized none of the 34 non-P. gingivalis strains.
      Rabbit antisera were similarly specific for P. gingivalis cells in
      immunofluorescence and with LPS in grid-blotting, but several of them recognized
      LPS from one Prevotella melaninogenica and 5 Prevotella intermedia strains in
      Western blotting. Since several pre-immune sera and an irrelevant serum raised to
      a Streptococcus species recognized up to 5 of these preparations, we exclude that
      the reactions were due to antigens shared by P. gingivalis and Prevotella.
      Rather, we consider that they were false-positive reactions due to natural
      antibodies, stimulated in a non-specific manner upon immunization with P.
      gingivalis, in animals whose immune systems were sensitized to Prevotella species
      before immunization.

PMID- 7513000
TI  - Peptidergic neurons in the snail Helix pomatia: distribution of neurons in the
      central and peripheral nervous systems that react with an antibody raised to the
      insect neuropeptide, leucokinin I.
AB  - In this study, an antiserum raised against an insect myotropic peptide,
      leucokinin I (DPAFNSWGamide), was used for mapping leucokinin-like immunoreactive
      (LK-LI) neurons in the gastropod mollusc, Helix pomatia. Immunocytochemistry
      performed on both whole-mounts and cryostat sections demonstrated LK-LI neurons
      in all ganglia of the central nervous system (CNS), except the visceral ganglion.
      Altogether about 700 immunolabelled neurons have been found, with nearly one-half
      (46%) in the cerebral ganglia. A large proportion of the LK-LI neurons have small
      cell bodies and are likely to be interneurons. The most prominent LK-LI cell
      group is represented by the entire neuron population of the mesocerebri, which is
      the major source of a thick fiber bundle system, encircling and innervating the
      whole CNS. One single LK-LI giant neuron was found, which is located in the left
      pedal ganglion and is termed GLPdLKC (giant left pedal leucokinin immunoreactive
      cell). This cell has not been identified previously. The ganglion neuropils are
      heavily innervated by varicose LK-LI fiber arborizations. Some integrative
      centers, such as the medullary neuropil of the procerebri, reveal an extreme
      density of LK-LI innervation. All major peripheral nerves contain a large number
      of LK-LI axons, and LK-LI innervation is found in the musculature of different
      peripheral organs (buccal mass, lip, tentacles, oviduct, intestine). Among the
      peripheral organs investigated, the intestine contains a rich varicose LK-LI
      network, composed of both intrinsic and extrinsic elements. Radioimmunoassay
      (RIA) demonstrates a very high content of LK-LI material in Helix ganglion
      extracts (about 50 pmol/CNS). This is the first report on the occurrence of a
      substance resembling the myotropic neuropeptide leucokinin I in a phylum outside
      arthropods. Based on our immunocytochemical observations, a role for leucokinin
      like peptides in both central and peripheral regulatory processes in Helix is
      suggested. According to double-labelling experiments, only a small number of the
      LK-LI neurons are labelled with an antibody to the vertebrate tachykinin
      substance P.

PMID- 7512999
TI  - Excitatory amino acid antagonists protect cochlear auditory neurons from
      excitotoxicity.
AB  - Since ischemic damage in the brain is linked to glutamate excitotoxicity, the
      effects of an acute exposure to glutamate, alpha-amino-3-hydroxy-5-methyl-4
      isoxazole proprionic acid (AMPA) or N-methyl-D aspartate (NMDA) on the radial
      dendrites were compared with those occurring after a severe cochlear ischemia.
      Glutamate and AMPA, but not NMDA, produced a drastic swelling restricted to the
      radial dendrites below the inner hair cells (IHCs). At a concentration of 20
      microM AMPA, a full electrophysiological recovery could be observed in some
      cochleas after washing the drug out. A prior perfusion of 6-7-dinitroquinoxaline
      2,3-dione (DNQX, 50 microM) prevented the 25 microM AMPA-induced dendritic
      swelling. No protective effect of D-2-amino-5-phosphonopentanoate (D-AP5) could
      be observed. In the same way, ischemia (5-40 minutes) resulted in a clear
      swelling of the radial dendrites. While D-AP5 had no protective effects, 50
      microM DNQX protected most of the radial dendrites from the ischemia-induced
      swelling, excepting those contacting the modiolar side of the IHCs. Finally, 50
      microM DNQX + 50 microM D-AP5 resulted in a nearly complete protection of all the
      radial dendrites. Altogether, these results suggest that the acute swelling of
      radial dendrites primarily occurs via AMPA/kainate receptors. However, in radial
      dendrites contacting the inner hair cells on their modiolar side, NMDA receptors
      may be also involved.

PMID- 7513004
TI  - Epitope specificity and immunoaffinity purification of the major peanut allergen,
      Ara h I.
AB  - The antigenic and allergenic structure of Ara h I, a major allergen of peanuts,
      was investigated with the use of seven monoclonal antibodies obtained from BALB/c
      mice immunized with purified Ara h I. Previous work with monoclonal antibodies
      produced to allergens has primarily been done with inhalant allergens. Only
      recently have the major allergens of various foods been determined so that
      investigations with monoclonal antibodies into the allergenic epitopes could
      begin. When used as a solid phase in an ELISA, these monoclonal antibodies
      captured peanut antigen, which bound human IgE from patients with positive
      results to challenges to peanuts. The Ara h I monoclonal antibodies were found to
      be specific for peanut antigens when binding for other legumes was examined. In
      ELISA inhibition studies with the monoclonal antibodies, we identified four
      different antigenic sites on Ara h I. In related studies with pooled human IgE
      serum from patients with positive results to challenges to peanuts, we identified
      three similar IgE-binding epitopes. As a means of purifying the Ara h I allergen,
      we prepared an immunoaffinity column with monoclonal antibody 8D9. We eluted from
      this column the allergen Ara h I, which had a mean molecular weight of 63.5 kd
      and which bound human IgE from individual and pooled serum of patients with
      peanut sensitivity.

PMID- 7513003
TI  - The effect of hydroxyethyl starch and other plasma volume substitutes on
      endothelial cell activation; an in vitro study.
AB  - OBJECTIVE: To study the effect of medium molecular weight hydroxyethyl starches
      on endothelial cell and neutrophil activation in vitro. SETTING: Laboratory
      analysis. METHODS: The effects of albumin and hydroxyethyl starch on the
      neutrophil adhesion molecule (CD11bCD18), with and without lipopolysaccharide
      stimulation, were studied in whole blood. E-selectin expression on human
      umbilical vein endothelial cells was stimulated with lipopolysaccharide alone and
      in the presence of either albumin or hydroxyethyl starch. The effect of albumin
      and hydroxyethyl starches on rapid endothelial cell activation was studied using
      von Willebrand factor release as a marker. MEASUREMENTS AND RESULTS: Hydroxyethyl
      starches but not albumin inhibited stimulated vWF release in a dose dependent
      manner. No effect was seen on endothelial E-selectin or neutrophil CD11bCD18
      expression. CONCLUSIONS: these results suggest a possible beneficial role of
      hydroxyethyl starches in the inhibition of endothelial activation thus preventing
      neutrophil adhesion during sepsis syndrome.

PMID- 7513005
TI  - The vascular endothelium in septic shock.

PMID- 7513006
TI  - Solubilization of keratin debris in conservative treatment of middle ear
      cholesteatoma: an in vitro study.
AB  - A variety of solutions were tested in vitro to find a suitable solvent which
      could be used in clinical practice for cholesteatoma debris. Though a little weak
      as a solvent, a liquid soap composed mainly of plant oil did not cause irritation
      of the middle ear mucosa, and was thought to be a promising solvent with which to
      rinse away tenacious debris, especially when used in combination with hydrogen
      peroxide.

PMID- 7513007
TI  - Prostatic adenocarcinoma metastatic to the palatine tonsil: a case report.
AB  - A case of prostatic adenocarcinoma presenting with dysphagia due to a tonsillar
      metastasis is described. Details of the clinical history, histopathological and
      autopsy findings are presented. A review of the literature suggests that this is
      only the second description of such an occurrence.

PMID- 7513008
TI  - Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma.
AB  - We investigated the role of interleukin 8 (IL-8) in mediating angiogenesis in
      human bronchogenic carcinoma. Increased quantities of IL-8 were detected in tumor
      tissue as compared with normal lung tissue. Immunohistochemical staining of
      tumors revealed primary localization of IL-8 to individual tumor cells and
      demonstrated the capacity of tumor to elaborate IL-8. Functional studies that
      used tissue homogenates of tumors demonstrated the induction of both in vitro
      endothelial cell chemotaxis and in vivo corneal neovascularization. It is
      important to note that the addition of neutralizing antisera to IL-8 to these
      assays resulted in the marked and specific attenuation of these responses. Our
      observations definitively establish IL-8 as a primary mediator of angiogenesis in
      bronchogenic carcinoma and offer a potential target for immunotherapies against
      solid malignancies.

PMID- 7513010
TI  - Small splenic B cells that bind to antigen-specific T helper (Th) cells and face
      the site of cytokine production in the Th cells selectively proliferate:
      immunofluorescence microscopic studies of Th-B antigen-presenting cell
      interactions.
AB  - Antigen (Ag)-specific T helper (Th) cells regulate the proliferation and
      differentiation of Ag-specific B cells by secreting cytokines and by expressing
      activating receptors like gp39. In vitro, the cytokines and the activating
      receptors function in an Ag-nonspecific manner. It is unclear, therefore, how Ag
      specificity is imposed on B cell responses in physiological Th-B cell
      interactions. Here we studied, at the single cell level, the interactions between
      cloned Th cells and small splenic B cells, which served as Ag-specific antigen
      presenting cells (APCs) to the Th cells. Digital confocal immunofluorescence
      microscopy of Th-B cell conjugates revealed significant variability in the
      molecular and cellular properties of these interactions, in spite of the fact
      that all the interactions in this system were expected to be Ag specific. After
      30 h of incubation B cells began to divide, and this process was entirely
      dependent on the presence of both Th cells and Ag. Immunofluorescence microscopic
      studies showed that essentially all the mitotic B cells were bound to Th cells
      and faced the microtubule organizing center (MTOC) in the Th cells where
      interleukin 4 was highly concentrated. Other B cells that were bound to the same
      Th cells but were not close to the Th-MTOC remained in interphase. These results
      provide the first direct structural and functional evidence that the site of
      interaction of B cells with Th cells affects their immune response. We propose
      that, during Ag-induced Th-B cell interactions, B cells that are bound facing the
      Th-MTOC proliferate preferentially because they are the recipients of locally
      secreted cytokines. In addition, these B cells may interact with newly expressed
      receptors, which may also be locally inserted into the Th membrane. The polarized
      delivery of activating molecules towards the Th-bound APCs may impose functional
      specificity on effector molecules that otherwise are not Ag specific.

PMID- 7513009
TI  - CD54/intercellular adhesion molecule 1 and major histocompatibility complex II
      signaling induces B cells to express interleukin 2 receptors and complements help
      provided through CD40 ligation.
AB  - We have examined signaling roles for CD54 intercellular adhesion molecule 1 and
      major histocompatibility complex (MHC) II as contact ligands during T help for B
      cell activation. We used a T helper 1 (Th1)-dependent helper system that was
      previously shown to be contact as well as interleukin 2 (IL-2) dependent to
      demonstrate the relative roles of CD54, MHC II, and CD40 signaling in the events
      leading to the induction of B cell proliferation and responsiveness to IL-2.
      Paraformaldehyde-fixed activated Th1-induced expression of IL-2R alpha, IL-2R
      beta, and B7, and upregulated MHC II and CD54 on B cells. Anti-CD54 and MHC II
      mAbs as well as a CD8 alpha-CD40 ligand (L) soluble construct inhibited both the
      T-dependent induction of Ig secretion, and B cell phenotypic changes. We then
      compared the effects of activated Th1 cells with that of cross-linking these
      molecules. Cross-linking of CD54 and MHC II resulted in the upregulated
      expression of MHC II and of CD54 and B7, respectively, analogous to the effect of
      fixed activated Th1 cells. B7 expression was further enhanced by co-cross-linking
      CD54 and MHC II. Cross-linking of CD40 achieved comparable effects. Strikingly,
      cross-linking ligation of CD54 and MHC II in the presence of IL-5 induced
      expression of a functional IL-2R on small resting B cells. By contrast CD40
      ligation, which induced B cell proliferation, did not induce IL-2 responsiveness.
      These data show that CD40 ligation is necessary but may not be sufficient for B
      cell differentiation and identify CD54 and MHC II as contact ligands that can
      complement CD40 signaling in the generation of T-dependent B cell responses to IL
      2.

PMID- 7513011
TI  - Functional and antigenic similarities between a 94-kD protein of Schistosoma
      mansoni (SCIP-1) and human CD59.
AB  - Schistosomiasis is a parasitic disease affecting approximately 200 million
      people, primarily in the third world. Schistosoma mansoni, one of the causative
      agents of this disease, parasitize the human mesenteric and portal blood systems
      while successfully evading host immune responses. During parasite penetration
      into the mammalian host and shortly afterwards, the larvae rapidly convert from
      being sensitive to being resistant to C-mediated killing. Treatment of the C
      resistant parasitic forms with trypsin renders the parasite susceptible to C
      attack, thus indicating the presence of C inhibitory protein(s) on the parasite
      surface. We describe here an intrinsic schistosome C inhibitory protein (SCIP-1)
      that exhibits antigenic and functional similarities with the human C-inhibitor
      CD59. Like CD59, SCIP-1 is capable of inhibiting formation of the C membrane
      attack complex (MAC), probably by binding to C8 and C9 of the C terminal pathway.
      In addition, SCIP-1 is apparently also membrane-anchored via glycosyl
      phosphatidylinositol as it can be specifically released with phosphatidylinositol
      specific phospholipase C. Soluble SCIP-1, partially purified from Nonidet P-40
      extracts of schistosome tegument is capable of inhibiting hemolysis of sensitized
      sheep erythrocytes and of rabbit erythrocytes by human C. Anti-human CD59
      antibodies block this activity of SCIP-1 and in addition, upon binding to intact
      parasites, render them vulnerable to killing by human and guinea pig C. SCIP-1 is
      located on the surface of C-resistant forms of the parasite, i.e., 24-h cultured
      mechanical schistosomula and in vivo-derived adult worms as revealed by
      immunofluorescence and immunogold electron microscopy studies. These results
      identify one of the mechanisms schistosomes use to escape immune attack.

PMID- 7513012
TI  - Holes in the T cell repertoire to myelin basic protein owing to the absence of
      the D beta 2-J beta 2 gene cluster: implications for T cell receptor recognition
      and autoimmunity.
AB  - Models of T cell recognition suggest that amino acid residues in the CDR3 region
      of the T cell receptor (TCR) alpha or beta chain directly contact the major
      histocompatibility complex-bound peptide, and thus are crucial for providing
      peptide specificity. T cells derived from B10.PL or PL/J mice of H-2u haplotype,
      use only D beta 2 and J beta 2 gene segments in the recognition of the dominant
      determinant, Ac1-9/Au, of myelin basic protein (MBP). New Zealand White (NZW)
      mice, with identical class II H-2u genes (I-A and I-E), carry an 8.8-kb deletion
      in their TCR beta chain locus encompassing D beta 2 and J beta 2 gene segments.
      How does this deletion of the crucial D beta 2-J beta 2 region in NZW mice
      influence specific responses to Ac1-9/Au as well as to other known Au or Eu
      determinants of MBP? We found that these mice respond very poorly to the dominant
      Ac1-9/Au and to the subdominant 31-50/Eu determinant in in vitro proliferation
      assays as well as in their in vivo capacity to induce experimental autoimmune
      encephalomyelitis. This loss of response is apparently owing to the absence of
      high avidity TCRs with essential CDR3 residues contributed by D beta 2 or J beta
      2 gene segments. These data reveal constraints in the recognition of certain
      antigenic structures, and further support a TCR-recognition model in which CDR3
      residues of the TCR alpha and beta chains constitute the antigenic peptide
      binding sites on the TCR molecule. Implications for autoimmune manifestations
      contributed by NZW genes in (NZB x NZW)F1 disease are also discussed.

PMID- 7513013
TI  - Upregulation of mouse CD14 expression in Kupffer cells by lipopolysaccharide.
AB  - Western blot analysis showed that a monoclonal antibody against recombinant mouse
      CD14 (mCD14), designated rmC5-3, specifically reacted with mouse macrophage cell
      line J774, but not myeloma cell line NS1. Fluorographic and immunocytochemical
      analysis demonstrated specific binding of rmC5-3 with mouse resident macrophages,
      inflammatory monocytes and neutrophils, and macrophage cell lines.
      Immunohistochemical staining using rmC5-3 showed that CD14-positive Kupffer cells
      (KC) were small in number in the liver in nonstimulated mice. The number of
      stained KC, which were rich in the midzonal and periportal regions, gradually
      increased with time after intraperitoneal injection of lipopolysaccharide (LPS),
      peaked 6 h after injection, and returned to normal by 20 h after injection.
      Staining intensity over time was proportional to the number of KC. A slight
      increase in mCD14 expression was observed in peritoneal macrophages 2 h after LPS
      administration in vivo using flow cytometric analysis. mCD14 mRNA became
      detectable at 1 h after the intraperitoneal injection of LPS (20
      micrograms/mice), and the level dramatically increased with time, peaking at 3 h,
      and sharply dropped at 6 h. The resident peritoneal macrophages demonstrated a
      constitutively high mCD14 mRNA expression, which slightly increased 2 h after LPS
      (100 ng/ml) stimulation in vitro. The level of mCD14 expression in macrophages
      did not increase after intraperitoneal injection of LPS (20 micrograms/mice).

PMID- 7513014
TI  - Human osteoblasts support hematopoiesis through the production of granulocyte
      colony-stimulating factor.
AB  - Previous attempts at identifying the constitutive source(s) of granulocyte colony
      stimulating factor (G-CSF) in human bone marrow have been unsuccessful despite
      the fact that normal bone marrow supports abundant myelopoiesis in vivo. We
      hypothesized that the intimate physical association between bone and
      hematopoietic cells facilitates interactions between osteoblasts and
      hematopoietic stem cells. Here we provide the first direct evidence that human
      osteoblasts participate in hematopoiesis by constitutively producing G-CSF and
      present the protein in a membrane-associated fashion to human hematopoietic
      progenitors. These results suggest a direct and central role for osteoblasts in
      normal myelopoiesis.

PMID- 7513015
TI  - NH2-terminal sequence of macrophage-expressed natural resistance-associated
      macrophage protein (Nramp) encodes a proline/serine-rich putative Src homology 3
      binding domain.
AB  - The Lsh/Ity/Bcg locus on mouse chromosome 1 regulates macrophage (m phi)
      priming/activation for antimicrobial activity against intracellular pathogens. A
      candidate Bcg gene, designated natural resistance-associated m phi protein
      (Nramp), recently isolated from a pre-B cell cDNA library encodes a polytopic
      integral membrane protein with structural features common to prokaryotic and
      eukaryotic transporters. In the present study, an activated m phi cDNA library
      yielded new Nramp clones that differ in the 5' region from the published pre-B
      cell-derived clone sequence, resulting in addition of 64 amino acids at the NH2
      terminus of the predicted protein. This new domain is rich in proline, serine,
      and basic amino acids, and includes three protein kinase C phosphorylation sites
      and a putative Src homology 3 binding domain. RNAs containing this domain are the
      only form found in the m phi. Hence, the protein encoded by this RNA is the
      candidate molecule mediating natural resistance to intra-m phi pathogens.

PMID- 7513016
TI  - Production of the RANTES chemokine in delayed-type hypersensitivity reactions:
      involvement of macrophages and endothelial cells.
AB  - To understand the selective accumulation of memory T helper lymphocytes and of
      macrophages in delayed-type hypersensitivity (DTH) granulomas, we studied the in
      situ production of RANTES, a chemokine initially characterized on the basis of
      its in vitro chemotactic properties for each of these cell populations. RANTES
      gene expression was studied by in situ hybridization in 15 human lymph nodes
      presenting typical DTH lesions related to either sarcoidosis or tuberculosis. A
      positive signal was detected in all cases. Labeling was specific for the DTH
      lesions, as very few if any positive cells were detected in the normal residual
      lymphoid tissue surrounding them or in reactive lymph nodes involved in a B
      lymphocyte response. RANTES gene expression was associated with the production of
      the protein, which was detected by immunochemistry in DTH lymph nodes. The
      morphological characteristics and distribution of positive cells in in situ
      hybridization and immunochemical experiments indicated that macrophages and
      endothelial cells, two cell populations not previously reported to produce
      RANTES, contributed to its production in DTH reactions. The ability of
      macrophages and endothelial cells to produce RANTES was confirmed by in vitro
      studies with alveolar macrophages and umbilical vein endothelial cells. In view
      of the chemotactic properties of RANTES for a limited range of cell populations,
      these results suggest that RANTES production in DTH granulomas may play a role in
      the selective accumulation of macrophages and memory T helper lymphocytes
      characterizing this type of cell-mediated immune reaction, and that macrophages
      and endothelial cells are involved in this production.

PMID- 7513017
TI  - Syk activation by the Src-family tyrosine kinase in the B cell receptor
      signaling.
AB  - Signaling through the B cell antigen receptor (BCR) results in rapid increases in
      tyrosine phosphorylation on a number of proteins. The BCR associates with two
      classes of tyrosine kinase: Src-family kinase (Src-protein-tyrosine kinase [PTK];
      Lyn, Fyn, Blk, or Lck) and Syk kinase. We have investigated the interaction
      between the Src-PTK and the Syk kinase in the BCR signaling. In contrast to wild
      type B cells, BCR-mediated tyrosine phosphorylation of Syk and activation of its
      in vitro kinase activity were profoundly reduced in lyn-negative cells. The
      requirement of the Src-PTK to induce tyrosine phosphorylation and activation of
      Syk was also demonstrated by cotransfection of syk and src-PTK cDNAs into COS
      cells. These results suggest that the Src-PTK associated with BCR phosphorylates
      the tyrosine residue(s) of Syk upon receptor stimulation, enhancing the activity
      of Syk.

PMID- 7513018
TI  - Reinfusion and serial measurements of carboplatin-mobilized peripheral-blood
      progenitor cells in patients receiving multiple cycles of high-dose chemotherapy.
AB  - PURPOSE: To examine the ability of carboplatin to mobilize peripheral-blood
      progenitor cells (PBPCs) and to examine the impact of infusing these cells on
      myelosuppression following multiple cycles of high-dose therapy. Fluctuations in
      circulating progenitor cell concentration following repeated cycles of this
      therapy were also measured. PATIENTS AND METHODS: Eight patients received a total
      of 20 cycles of carboplatin 1,200 mg/m2 per course, granulocyte-macrophage colony
      stimulating factor (GM-CSF) 5 micrograms/kg/d, and PBPC reinfusion every 28 days.
      PBPC were collected following 1 week of GM-CSF and following the first and second
      cycles of chemotherapy. Hematologic toxicity was correlated with the number of
      progenitor cells reinfused per cycle. The concentration of PBPC per milliliter of
      blood was measured at study entry, following GM-CSF priming, and after each cycle
      of chemotherapy. RESULTS: We observed a strong inverse correlation between the
      number of PBPCs (CD34 and colony-forming unit granulocyte-macrophage [CFU-GM]),
      but not mononuclear cells (MNCs) reinfused and the days with neutropenia less
      than 500/microL and platelets less than 20,000/microL. Compared with baseline
      levels, the circulating PBPC concentration increased up to 27-fold following the
      first course of chemotherapy, but decreased toward, and eventually below,
      baseline following the second and third cycles of carboplatin. CONCLUSION: PBPC
      reinfusion directly correlated with a reduction in myelosuppression following
      high-dose carboplatin chemotherapy. While high-dose carboplatin plus GM-CSF leads
      to a substantially greater mobilization of PBPC than GM-CSF alone, this effect is
      lost after multiple treatment cycles. These results emphasize the importance of
      early procurement and value of PBPC reinfusion in conjunction with multiple
      cycles of dose-intensive chemotherapy.

PMID- 7513020
TI  - Rapid measurement of serum pancreatic amylase.
AB  - A simple, rapid assay for the pancreatic isoenzyme of human serum amylase was
      developed. The assay utilized an immunoabsorbent prepared by coating latex beads
      with a monoclonal antibody specific for pancreatic amylase. Treatment of patient
      serum with immunoabsorbent removed pancreatic amylase, and measurement of
      residual amylase activity with standard total amylase methodology allowed
      estimation of the pancreatic amylase content. Extraction efficiency of pancreatic
      amylase was consistent at amylase concentrations up to 1,000 U/L (y = 0.97 x
      +16.7 U/L; r = 0.9995). The assay was standardized with purified pancreatic
      amylase added to neonatal serum (low endogenous activity). A comparison of
      patient specimen results with the results of a standard technique (cellulose
      acetate electrophoresis) yielded an excellent correlation (immunoabsorption
      result = 0.96 electrophoresis result + 1.2 U/L; r = 0.987). Salivary amylase did
      not interfere with the assay until levels exceeded 1,000 U/L. Daily analysis of a
      frozen serum pool yielded a coefficient of variation of 9.2% at mean pancreatic
      amylase value of 54 U/L (+/- 5 U/L). A normal range study found a strong
      influence of age, with pancreatic amylase levels increasing dramatically in the
      first 3 years of life, to stabilize at a range of 0-66 U/L thereafter.

PMID- 7513021
TI  - Assay for prostate specific antigen (PSA): problems and possible solutions.
AB  - The absolute tissue specificity of prostate specific antigen (PSA) allows the use
      of PSA test not only for detecting recurrence or metastasis at an early stage
      after radical prostatectomy but also for screening prostate cancer if combined
      with digital rectal examination. There is also a need to improve the current PSA
      test to better differentiate between prostate cancer and benign prostate
      hyperplasia (BPH). Because of these clinical applications, a much greater demand
      was placed on PSA test for extra sensitivity, accuracy, and precision even within
      the normal PSA concentration range. However, the current commercial assay kits
      for PSA do not provide correct PSA values. Many factors contributing to the
      problem include the specificity of the anti-PSA antibodies, the composition of
      the calibrator, the PSA values assigned to the calibrator, the PSA isoform used
      for anti-PSA antibody preparation, the test design, and the composition of the
      diluent. Most problems were derived from the failure of realizing earlier that
      the majority of the PSA exists in serum not as free PSA but as complexes with
      protease inhibitors. Other problems, such as constantly changing composition of
      various forms of PSA in serum specimens, and different clearance rates for
      various forms of PSA make almost impossible to develop an ideal assay for PSA.
      Therefore, we suggest that test should be designed for measuring PSA-ACT (PSA
      alpha 1-antichymotrypsin) complex only. Changing the focus from the measurement
      of total PSA of various forms to the PSA-ACT complex alone may improve the
      differentiation between prostate cancer and BPH but may also simplify the
      selection of anti-PSA antibodies and the preparation of calibrator for the assay.

PMID- 7513019
TI  - Recent advances in immunobiology of brain tumors.

PMID- 7513022
TI  - Role of cytokine in the induction of adhesion molecules on cultured human
      gingival fibroblasts.
AB  - This study was undertaken in an effort to understand the role of cytokines on
      human gingival fibroblasts and T lymphocyte trafficking into inflamed gingival
      tissue. Using flow cytometry we examined gingival fibroblasts to determine the
      level of cell surface expression and the percentage of cells positive for
      intercellular adhesion molecule 1 (ICAM-1), the HLA-DR antigen, lymphocyte
      function-associated antigen 3 (LFA-3), and the CD44 molecule, which are involved
      in antigen presentation. The following cytokines were used: interleukin-1 beta
      (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN
      gamma), IL-6, and IL-8. The levels of ICAM-1 expression were enhanced in a dose-
      and time-dependent manner by IL-1 beta, TNF-alpha, or IFN-gamma, but not by IL-6
      or IL-8. HLA-DR surface expression was induced only by IFN-gamma in a dose- and
      time-dependent manner, but not by the other cytokines tested. In contrast, the
      expression of LFA-3 and the CD44 molecule could be detected without the
      stimulation of any cytokine, but the levels of their expression were not
      significantly changed by any cytokines. The enhanced ICAM-1 expression by
      cytokines was reduced in a time-dependent manner following the removal of
      cytokines from the reaction mixture, while IFN-gamma-induced HLA-DR expression
      was maintained even 7 days after the removal of IFN-gamma. These data support an
      interactive role for inflammatory cytokines and the expression of adhesion
      molecules on gingival fibroblasts in the pathogenesis of gingival inflammation in
      periodontal disease.

PMID- 7513023
TI  - Antibody response against epitopes on hCG mapped by monoclonal antibodies in
      women immunized with an anti-hCG vaccine and its implications for
      bioneutralization.
AB  - The immunological determinants on hCG, to which an antibody response is generated
      in women by the contraceptive HSD vaccine, were mapped by using a panel of anti
      hCG monoclonal antibodies. Two types of inhibition enzyme immunoassays (EIAs)
      were used to analyze 126 serum samples from 18 subjects immunized with the
      vaccine and protected from pregnancy. Monoclonal antibody (MAb) 357-2, which
      recognizes beta-hCG loop peptide 38-57, did not inhibit significantly the binding
      of immune sera to hCG. Moreover, none of the sera reacted with this loop peptide
      in a direct binding EIA, suggesting weak immunogenicity of this epitope. All sera
      competed with MAb 206 and a preponderance of antibodies was seen against this
      epitopic region on beta-hCG. The antibody titers against the MAb 206 epitope
      showed a good correlation with the bioneutralization capacity of the sera
      throughout the course of immunization. These studies indicate the presence of an
      immunodominant antigenic determinant on hCG as recognized by the human immune
      system.

PMID- 7513026
TI  - Disability abated: audio-cassettes for the visually impaired.
AB  - The paper reports on aspects of a nation-wide interview study of a sample of 320
      visually impaired people. Visually impaired people are evidently keen to keep
      abreast of news and current affairs. They answer their needs in this respect to a
      modest extent through braille material, and on a large scale by means of
      television and especially radio. Audio-cassettes play a surprisingly important
      role, particularly recordings of newspapers and other periodicals. They are used
      regularly by a large majority of blind people. Reactions to audio-cassettes are
      enormously positive. They appear to provide not only information, but also
      companionship, purpose and meaning. The survey suggests that need and demand for
      a nation-wide audio-cassette service is substantial.

PMID- 7513025
TI  - In vitro IgM rheumatoid factor production by peripheral blood mononuclear cells
      from patients with seronegative rheumatoid arthritis.
AB  - OBJECTIVE: We investigated whether mononuclear cells (MNC) from patients with
      seronegative rheumatoid arthritis (SNRA) are able to produce rheumatoid factor
      (RF) in response to lectin stimulation, Staphylococcus aureus Cowan I (SAC) or
      pokeweed mitogen (PWM), and also we investigated the role of CD5+ B cells in the
      pathogenesis of in vitro IgM RF production. METHODS: IgM RF production was
      measured by enzyme linked immunosorbent assay and CD5+ B cells by flow cytometry.
      Also, the effects of monocyte depletion and the inhibition of prostaglandin (PG)
      were compared in SNRA, seropositive RA (SPRA) and healthy controls. RESULTS:
      Peripheral blood MNC of patients with SNRA were able to produce the same amount
      of IgM RF as patients with SPRA following stimulation and SAC. CD5+ B cells also
      increased in patients with SNRA as well as patients with SPRA compared to healthy
      controls. However, a definite contribution of the CD5+ B cells to SAC-induced IgM
      RF production could not be demonstrated. The role of macrophage and PG on in
      vitro IgM RF synthesis were insignificant. CONCLUSION: MNC of patients with SNRA
      were able to produce IgM and IgG RF in response to SAC stimulation as well as
      that of the healthy controls. However, we could not find a significant role of
      CD5+ B cells and monocytes on in vitro IgM RF synthesis by MNC of patients with
      SNRA.

PMID- 7513024
TI  - Inhibition of fertility in female mice by immunization with a B-cell epitope, the
      synthetic sperm peptide, P10G.
AB  - Human patient sera containing antisperm antibodies (from vasectomized men and
      infertile women) immunologically react with the synthetic peptide P10G
      (PGGGTLPPSG), and affinity purified antibodies to P10G (anti-P10G) react with
      human spermatozoa (O'Rand et al., 1990). In this study P10G was used to elicit
      antibodies and the effect of the antibodies on fertility in female mice
      determined. The P10G sequence is derived from the 14-kDa rabbit sperm
      autoantigen, RSA (O'Rand and Widgren, 1990). The results of this study
      demonstrate that female mice can become infertile when immunized with the
      synthetic peptide P10G conjugated to the carrier protein keyhole limpet
      hemocyanin (KLH). However, the results also show that it is important to
      distinguish those mice with high serum antibody levels from those with lower
      levels. Infertility was clearly apparent in the high titer subgroup with an 80%
      decrease in pregnancy rate during the last of three matings and a 71% decrease in
      litter size over all three matings when compared to the low titer subgroup or the
      control groups. Significantly, mice immunized with P10G without carrier protein
      show no detectable antigen specific proliferation of lymph node cells in response
      to 100 microM of the peptide. P10G is not a T-cell epitope, but rather a B-cell
      epitope and it does not elicit an autoimmune response in the female mouse. This
      demonstration in mice is an important first step in the development of a safe
      human immunocontraceptive vaccine.

PMID- 7513027
TI  - Design and synthesis of RNA-specific groove-binding cations: implications for
      antiviral drug design.
AB  - As as initial step in the design of structure-specific RNA-interactive molecules
      as potential antiviral agents, we have focused on the synthesis of molecules that
      exhibit strong and preferential binding to duplex RNA. A series of polycationic
      ligands have been synthesized, and the degree of preferential binding to RNA has
      initially been determined by thermal denaturation (delta Tm) with both RNA
      [poly(A).poly(U)] and DNA [poly(dA).poly(dT)] polymers at a variety of pH values.
      Seven compounds from the series exhibit a substantial degree of RNA-selective
      binding. The relatively high delta Tm values obtained suggest a specific mode of
      interaction between these ligands and the RNA helix. By contrast, the much lower
      delta Tm values with poly(dA).poly(dT) DNA reflect a more nonspecific interaction
      mode. A viscometric titration study with poly(A).poly(U) confirms that they do
      not bind by intercalation. The results, combined with the known structure and
      electronegative potential of duplex RNA, suggest that these molecules bind in the
      major groove via specific electrostatic and/or hydrogen-bonded interactions.

PMID- 7513028
TI  - The role of circulating cells in the healing of vascular prostheses.
AB  - PURPOSE: Cells covering the flow surface of vascular prostheses are derived in
      part from endothelium of adjacent native artery and from capillaries that extend
      through the pores of the graft. This study is designed to determine whether these
      endothelial-like cells can also originate from circulating blood cells and if so
      to identify them with protein markers. METHODS: Pledgets of vascular graft
      material were suspended within the aortas of dogs with metal stents that isolated
      the pledgets from the aortic wall. Explanted pledgets were examined for cells
      containing factor VIII-related antigen and other markers identified with
      monoclonal antibodies. RESULTS: A monolayer of cells that stained positive for
      factor VIII formed on pledgets after 7 days. Pledgets removed after 55 days had
      endothelial cells, smooth muscle cells, macrophages, monocytes, and capillary
      like structures which were identified by staining for the monoclonal antibodies
      43 beta E3 (vimentin), HHF35 (alpha and gamma muscle actin), CGA7 (smooth muscle
      actin), and HAM56 (macrophage). Woven and knitted polyester and extruded
      polytetrafluoroethylene pledgets healed in a similar manner. CONCLUSION: The
      origin of the cells identified is speculative but they appear to have been
      derived from circulating cells, possibly stem cells, which are capable of
      differentiation because the pledgets on which the cells were identified were
      isolated from aortic wall endothelium and perivascular capillaries.

PMID- 7513029
TI  - Decreases in substance P and vasoactive intestinal peptide concentrations in
      plasma of stroke-prone spontaneously hypertensive rats.
AB  - In order to study alterations of peripheral substance P (SP) and vasoactive
      intestinal peptide (VIP) in the immunoreactive nervous system in essential
      hypertension, plasma SP and VIP concentrations in stroke-prone spontaneously
      hypertensive rats (SHRSP) at 8, 12, 18, 28, 30, 35 and 48 weeks of age and age
      matched Wistar-Kyoto rats (WKY) were measured, using enzyme immunoassays (EIAs).
      The mean plasma SP concentrations of SHRSP (n = 61) and WKY (n = 58) were 4.9 +/-
      1.2 fmol/ml and 6.6 +/- 1.9 fmol/ml, respectively. The value of SHRSP was
      significantly lower than that of WKY (p < 0.01). The mean SP concentration of
      young SHRSP was significantly higher than those of other ages. The mean plasma
      VIP concentrations of SHRSP (n = 61) and WKY (n = 58) were 0.80 +/- 0.25 fmol/ml
      and 1.01 +/- 0.32 fmol/ml, respectively. The value of SHRSP was significantly
      lower than that of WKY (p < 0.01). These decreases in plasma SP and VIP
      concentrations of SHRSP were observed at all ages. Decreases in the peripheral
      release of SP and VIP from the endings of SP- and VIP-immunoreactive nerves of
      SHRSP were seen, and the functional involution of peripheral SP- and VIP
      immunoreactive nerves in essential hypertension was suggested.

PMID- 7513030
TI  - [Radioimmunoassay of synthetic steroid hormones].
AB  - The problem and recent progress of radioimmunoassay for various kinds of
      synthetic steroid hormones are reviewed. The specificity and sensitivity depend
      mostly on the position of synthetic antigen (hemisuccinate or oxime). Using good
      antibodies, a direct radioimmunoassay without extraction procedures of samples is
      available. A simplified method is required for the monitoring of synthetic
      steroids to know the effects and side effects.

PMID- 7513031
TI  - [Application of antiandrogens on prostatic diseases].
AB  - Antiandrogen therapy for benign prostatic hyperplasia (BPH) and prostatic
      carcinoma has been introduced in clinical practice. Steroidal antiandrogens such
      as progestational agents suppress prostatic growth through pituitary gonadotropin
      suppression as well as by blocking intraprostatic androgen action. Although
      clinical efficacy of the therapy appears to be promising in some clinical trials,
      the side effect of sexual function disturbances remains to be solved especially
      in BPH patients. The new treatment modality for advanced prostatic carcinoma has
      been introduced; the total androgen blockade therapy, utilizing a pure
      antiandrogen (Flutamide) in combination with an LH-RH agonist, has been proposed
      by some authors, but the overall efficacy has not been established yet. Clinical
      trials for two pure antiandrogens (Flutamide and Casodex) are currently in
      progress in Japan.

PMID- 7513032
TI  - Inhibitory effects of sialic acid- or N-acetylglucosamine-specific lectins on
      histamine release induced by compound 48/80, bradykinin and a polyethylenimine in
      rat peritoneal mast cells.
AB  - The effects of seven lectins with various sugar-specificities on histamine
      release from rat peritoneal mast cells induced by non-immunologic stimuli were
      studied. The non-immunologic stimuli used were three basic secretagogues,
      compound 48/80, bradykinin and PEI6 (polyethylenimine with a molecular weight of
      600). In this study, we observed inhibition of the histamine release by Macckia
      amurensis mitogen and Solanum tuberosum agglutinin (100 micrograms/ml at 37
      degrees C for 10 min), which are specific for sialic acid-alpha 2,3-N-acetyl
      galactosamine (Sia alpha 2,3GalNAc) and N-acetyl glucosamine (GlcNAc) oligomers,
      respectively. The effects of Phytolacca americana mitogen and Sambucus
      sieboldiana agglutinin were different. Three lectins specific for mucin type
      oligosaccharides inhibited the histamine release induced by compound 48/80 but
      not that induced by bradykinin or PEI6. Since bradykinin and PEI6 additively
      enhanced the histamine release induced by compound 48/80, they partially shared
      the same signalling pathways. Glycoproteins with bisecting GlcNAc and Sia
      residues, as described previously (Jpn. J. Pharmacol. 57, 79-90, 1991), seemed to
      be one of the action sites for compound 48/80, bradykinin and PEI6. In addition
      to the direct activation of the pertussis toxin-sensitive G proteins, we propose
      another mechanism of non-immunologic stimuli via specific glycoproteins on rat
      peritoneal mast cells. The apparent sugar residues involved were asparagine
      linked oligosaccharides with Sia (especially Sia alpha 2,3Gal), GlcNAc oligomers
      and/or bisecting GlcNAc.

PMID- 7513033
TI  - Effect of chronically increased erythrocyte complement receptors on immune
      complex nephritis.
AB  - Experimental studies in humans and other primates have shown that the erythrocyte
      (E) complement receptor Type 1 (CR1), which is unique to the primate, plays an
      important role in clearing immune complexes (IC) from the circulation by binding
      C3b/C4b opsonized immune complexes and carrying the IC to liver and spleen for
      disposal. The results of these acute experiments suggest that increasing E-CR1
      levels chronically should protect against IC-mediated glomerulonephritis (IC-GN)
      induced by chronic formation of IC in the circulation. In the present study this
      hypothesis was tested in the cynomolgus monkey (CYN). IC-GN was induced by daily
      bolus intravenous infusion of BGG into immunized CYN for 8, 10, or 14 weeks.
      Prior to and during the daily bolus infusions of BGG, sustained differences in E
      CR1 levels were achieved between the experimental group (increased E-CR1 levels)
      and the control group (maintained or decreased E-CR1 levels), by one of two
      methods: (1) Twice weekly exchange transfusion. The CYN donors were blood type
      compatible with the recipients and had either constitutive high E-CR1 expression
      (3,000 to 5,000 CR1/E) or constitutive low E-CR1 expression (< 100 CR/E). The
      recipients of the exchange transfusions (N = 2) had constitutive mid-level E-CR1
      expression. (2) Weekly phlebotomy (PL) or sham PL. CYN with mid-level E-CR1
      expression were randomly assigned to receive weekly either PL (causing increased
      E-CR1 expression by stimulating erythropoiesis) (N = 8) or sham PL (which has no
      effect on E-CR1 expression (N = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513034
TI  - Nitric oxide synthase: an endogenous source of elevated nitrite in infected
      urine.
AB  - To further define the endogenous sources of urine nitrite in urinary tract
      infections, we measured urinary nitrite levels by the Griess method and assayed
      urinary nitric oxide (NO) synthase activity by the conversion of 14C-arginine to
      14C-citrulline. Endogenous production of 14C-citrulline was confirmed by thin
      layer chromatography. Exogenous L-arginine increased nitrite production in whole
      infected urine, but not in bacteria isolated from infected urine. Urinary tract
      infections significantly increased NO synthase activity in soluble urine
      fractions, although soluble activity was less than 10% of particulate activity.
      Urine particulate fractions from women with non-infected urine had greater NO
      synthase activity than particulate fractions from men with non-infected urine, 11
      +/- 2 and 0.2 +/- 0.1 picomol/min/mg protein, respectively. Urinary tract
      infections increased NO synthase activity in urine particulate fractions from
      women and men, 99 +/- 20 and 48 +/- 9 picomol/min/mg protein, respectively. The
      conversion of 14C-arginine to 14C-citrulline required NADPH, was calcium
      independent, and was inhibited to a greater extent by L-canavanine than by NG
      monomethyl-L-arginine or NG-nitro-L-arginine. Human infected urine contains an
      isoform of NO synthase which is an endogenous source of urine nitrite.

PMID- 7513035
TI  - Direct demonstration of insulin-like growth factor-I-induced nitric oxide
      production by endothelial cells.
AB  - Several lines of evidence indicate that insulin-like growth factor-I (IGF-I) is a
      potent mediator of vasodilation. To elucidate the mechanism and site of action of
      IGF-I, we performed continuous monitoring of nitric oxide (NO) release from
      endothelial cells using a highly-sensitive amperometric NO-sensor. Two types of
      cultured cells were used: human umbilical vein endothelial cells and immortalized
      rat renal interlobar artery endothelial cells. In separate experiments, [Ca2+]i
      changes in response to IGF-I were measured spectrofluorometrically in fura-2
      loaded cells. Stimulation with IGF-I resulted in a rapid, dose-dependent increase
      in [NO] as detected by the NO-probe positioned 1 mm above the monolayers,
      followed by a sustained elevation lasting for at least five minutes. The effect
      of IGF-I was significantly suppressed by pretreatment with anti-IGF-I antibody,
      suggesting that it was specific for IGF-I. NG-nitro-L-arginine methyl ester, an
      inhibitor of NO synthesis, significantly blunted responses to IGF-I, but
      dexamethasone preincubation did not reduce the IGF-I-induced release of NO. These
      results indicate that the observed IGF-I-induced release of NO is a result of
      activation of the constitutive, rather than the inducible type of NO synthase in
      endothelial cells. Genistein, a tyrosine kinase inhibitor, resulted in a profound
      suppression of the IGF-I-induced release of NO. IGF-I did not affect [Ca2+]i in
      either type of cells. Therefore, IGF-I-induced NO production by both types of
      endothelial cells is mediated via a tyrosine kinase-dependent mechanism.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7513036
TI  - Clinical results and immunologic effects of a mixed bacterial vaccine in cancer
      patients.
AB  - A biological response modifier, mixed bacterial vaccine (MBV), derived from
      Streptococcus pyogenes and Serratia marcescens was used as a single agent in the
      treatment of 11 patients with refractory malignancies. MBV's effect on
      interleukin-2 (IL-2) production, plasma interferon (IFN) and tumor necrosis
      factor (TNF) levels was monitored. Most patients' peripheral blood mononuclear
      cells continued to produce baseline to elevated levels of IL-2, in spite of age
      and disease status. Several patients maintained moderate to high IFN levels. In
      general there was little correlation between IL-2 and IFN levels or with the
      response to therapy. One of 11 patients had minor response, 1 of 11 had partial
      response, 4 of 11 had temporary stabilization of disease, and 5 of 11 had
      progressive disease. A patient with AIDS and Kaposi's sarcoma experienced a
      dramatic improvement in performance status and disease stabilization. In all
      patients side effects occurred only following i.v. and not i.m. administration
      and included fever and chills. No adverse hepatic, renal or hematologic effects
      were observed. MBV is a well-tolerated biological response modifier with modest
      activity in advanced human tumors.

PMID- 7513037
TI  - Substance P enhances forskolin-stimulated cyclic AMP production in human UC11MG
      astrocytoma cells.
AB  - The effects of substance P (SP) upon basal and forskolin-stimulated cAMP
      production have been investigated in UC11MG cells. The cells expressed 40,000 NK1
      receptors/cell, the stimulation of which led to enhanced phosphoinositide
      breakdown. Forskolin (10 and 100 mcM) stimulated cAMP production, whereas SP (3
      and 300 nM) produced no significant increase in cAMP production. However, SP
      enhanced the response to forskolin, with an EC50 value of about 10 nM. The
      response to forskolin was also enhanced by physalaemin and eledoisin, and was
      sensitive to inhibition by (+/-)CP96345. It is concluded that in the UC11MG cell
      line, SP not only stimulates phosphoinositide breakdown but also enhances the
      cAMP response to forskolin, possibly via stimulation of NK1 receptors.

PMID- 7513038
TI  - Himbacine discriminates between putative muscarinic M1 receptor-mediated
      responses.
AB  - This study describes the antagonistic properties of himbacine, in comparison with
      those of pirenzepine, at muscarinic receptors mediating the depolarization of rat
      superior cervical ganglion, the inhibition of electrically-induced twitch
      contractions of rabbit vas deferens and the contraction of dog saphenous vein,
      currently classified as putative muscarinic M1 sites. The affinity of himbacine
      for the vas deferens site (pA2 8.08) was nearly ten times higher than those for
      the M1 receptors of rat ganglion and dog saphenous vein (pA2 7.14 and 7.16,
      respectively); affinity estimates for pirenzepine were similar throughout the
      different preparations. The present data are consistent with the allocation of
      ganglion and saphenous vein receptors into the M1 subclass; the profile of the
      vas deferens site, conversely, appears to be different, and possibly more closely
      related to that reported for the M4/m4 receptor.

PMID- 7513039
TI  - Cyclic AMP enhancing drugs modulate eicosanoid release from human alveolar
      macrophages.
AB  - The effect of the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX),
      salbutamol and sodium nitroprusside was evaluated regarding PGE2 and LTB4 release
      and cAMP and cGMP level in human alveolar macrophages obtained from controls and
      COPD patients. Basal levels per five million control- respectively COPD alveolar
      macrophages: cAMP 1.2 and 1.0 pmole; cGMP 8.4 and 9.1 fmole; PGE2 120 and 63 pg
      and LTB4 19.2 and 14.8 pg. In both populations IBMX increased cAMP level by 55
      93% and salbutamol+IBMX by 285-252%. Except for the 61% rise in LTB4 release by
      salbutamol+IBMX the drugs hardly affected PGE2 and LTB4 release from control
      macrophages. In COPD alveolar macrophages, however, IBMX and IBMX+salbutamol
      largely reduced PGE2 release (63 vs 11 pg per 10(6) cells) but less efficiently
      increased LTB4. In both macrophage populations sodium nitroprusside (SNP)
      substantially increased (3-4 fold) cGMP level but did not affect eicosanoid
      production. Present results indicate that drugs which enhance cAMP level decrease
      PGE2 release from COPD macrophages and stimulate the release of LTB4 a
      chemotactic mediator involved in bronchial inflammatory reactions.

PMID- 7513040
TI  - Stress-dependent changes in fibrinolysis, serotonin and platelet aggregation in
      rats.
AB  - The effects of different kinds of acute stress on collagen-induced whole blood
      platelet aggregation and fibrinolysis in relation to blood serotonergic measures
      were studied. In rats water-immersion restraint stress resulted in a shortening
      of euglobulin clot lysis time (ECLT), an increase in tissue plasminogen activator
      (tPA) activity with a concurrent fall in its inhibitor activity. Footshock caused
      rather a suppression in fibrinolysis with a prolongation of ECLT and a decline in
      tPA activity as well as a reduction in whole blood platelet aggregation induced
      by collagen. Serotonin (5-HT) level, a marker of a severity of stress, increased
      after footshock application with a concomitant rise in its major metabolite-5
      hydroxyindoleacetic acid (5-HIAA). This indicates an enhanced 5-HT metabolism.
      Following water-immersion restraint stress 5-HT and 5-HIAA levels did not differ
      from controls. In both groups of stressed animals an inverse correlation between
      tPA activity and blood serotonin was observed. Our data indicate that these types
      of stress may influence either fibrinolysis or peripheral serotonergic mechanism
      in different ways. Acute and severe stress such as footshock by causing an
      impairment in fibrinolysis and a rise in 5-HT may contribute to the pathogenesis
      of thrombosis and henceforth to the development of atherosclerosis.

PMID- 7513041
TI  - Expression of neuropeptides in experimental diabetes; effects of treatment with
      nerve growth factor or brain-derived neurotrophic factor.
AB  - Rats with streptozotocin-induced diabetes of 4 to 6 weeks duration showed a
      depletion of both substance P (P < 0.01) and calcitonin gene-related peptide (P <
      0.01) in the sciatic nerve. Since expression of both peptides is sensitive to
      nerve growth factor (NGF) in vitro we examined the effect of treatment of
      diabetic rats with NGF, which significantly increased the levels of both peptides
      in treated diabetic animals (P < 0.01 for both). Treatment of non-diabetic rats
      with a similar NGF regime raised the mean peptide levels to a value similar to
      that seen in treated diabetic rats but the change was not statistically
      significant. In vehicle-treated diabetic rats the depletions of sciatic nerve
      neuropeptides were accompanied by a significant (P < 0.05) reduction in the level
      of CGRP mRNA in the 4th and 5th lumbar dorsal root ganglia, this was accompanied
      by an analogous reduction in the mRNA for gamma-preprotachykinin A (gamma-PPT),
      which did not attain statistical significance. Treatment of diabetic rats with
      NGF also prevented the deficits in the levels of CGRP and gamma-PPT mRNA in the
      lumbar dorsal root ganglia (P < 0.05). Treatment of other diabetic rats with the
      related neurotrophin, brain-derived neurotrophic factor (BDNF), had no effect on
      the levels of substance P and calcitonin gene-related peptide in the sciatic
      nerve.

PMID- 7513042
TI  - Gene expression and secretion of insulin-like growth factor-II and insulin-like
      growth factor binding protein-2 from cultured sheep choroid plexus epithelial
      cells.
AB  - The gene expression of insulin-like growth factor II (IGF-II) and insulin-like
      growth factor binding protein-2 (IGFBP-2) has previously been demonstrated in rat
      and human choroid plexus by in situ hybridization analysis. In the present study
      we have characterized IGF-II and IGFBP-2 transcripts and proteins in primary
      cultures of epithelial cells from lateral choroid plexus of sheep brain. Northern
      blot analysis of total RNA showed one major IGF-II mRNA of 4.8 kb and four minor
      IGF-II transcripts of 1.5, 2.0, 3.0 and 6.0 kb as well as one IGFBP-2 transcript
      of 1.7 kb. Radioreceptor assay of conditioned medium from the cultured choroid
      plexus epithelial cells showed inhibition of [125I]IGF-I and [125I]IGF-II binding
      to mouse NIH 3T3 fibroblasts, the displacement curves being identical to that of
      unlabelled IGF-II. The conditioned medium was fractionated by gel filtration on a
      Bio-Gel P-60 column, and analysis by IGF-II radioreceptor assay showed two peaks
      of IGF-II-binding inhibitory activity of M(r) 7.5-10 and 25 kDa, suggesting the
      presence of both IGF-II, and an IGFBP. Western immunoblot analysis of conditioned
      medium with antibodies toward IGF-II and IGFBP-2 demonstrated proteins with M(r)
      6 kDa and 32 kDa, respectively. Protein binding assays of the conditioned medium
      with [125I]IGF-I or [125]IGF-II demonstrated that the IGFBP present in the
      conditioned medium preferentially binds IGF-II. In conclusion, cultured sheep
      choroid plexus epithelial cells synthesize and secrete IGF-II and IGFBP-2,
      suggesting that the choroid plexus epithelium is the main source of these
      polypeptides in the cerebrospinal fluid.

PMID- 7513044
TI  - [Nitric oxide--messenger substance and drug].

PMID- 7513043
TI  - Pulmonary toxicity associated with bleomycin.

PMID- 7513045
TI  - The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine
      kinase p56lck.
AB  - CD5 is a T-cell-specific antigen which binds to the B-cell antigen CD72 and acts
      as a coreceptor in the stimulation of T-cell growth. CD5 associates with the T
      cell receptor zeta chain (TcR zeta)/CD3 complex and is rapidly phosphosphorylated
      on tyrosine residues as a result of TcR zeta/CD3 ligation. However, despite this,
      the mechanism by which CD5 generates intracellular signals is unclear. In this
      study, we demonstrate that CD5 is coupled to the protein-tyrosine kinase p56lck
      and can act as a substrate for p56lck. Coexpression of CD5 with p56lck in the
      baculovirus expression system resulted in the phosphorylation of CD5 on tyrosine
      residues. Further, anti-CD5 and anti-p56lck coprecipitated each other in a
      variety of detergents, including Nonidet P-40 and Triton X-100. Anti-CD5 also
      precipitated the kinase from various T cells irrespective of the expression of
      TcR zeta/CD3 or CD4. No binding between p59fyn(T) and CD5 was detected in T
      cells. The binding of p56lck to CD5 induced a 10- to 15-fold increase in p56lck
      catalytic activity, as measured by in vitro kinase analysis. In vivo labelling
      with 32P(i) also showed a four- to fivefold increase in Y-394 occupancy in p56lck
      when associated with CD5. The use of glutathione S-transferase-Lck fusion
      proteins in precipitation analysis showed that the SH2 domain of p56lck could
      recognize CD5 as expressed in the baculovirus expression system. CD5 interaction
      with p56lck represents a novel variant of a receptor-kinase complex in which
      receptor can also serve as substrate. The CD5-p56lck interaction is likely to
      play roles in T-cell signalling and T-B collaboration.

PMID- 7513046
TI  - Definition of a lipopolysaccharide-responsive element in the 5'-flanking regions
      of MuRantes and crg-2.
AB  - Macrophages are stimulated by lipopolysaccharide (LPS) of gram-negative
      organisms. The changes in LPS-stimulated macrophages include transcriptional
      activation of multiple immediate-early genes, which may contribute to the natural
      immunity to microorganisms. We have defined by deletion and mutational analysis
      LPS-responsive elements (LREs) in two chemokine genes, MuRantes and crg-2, which
      are activated in an immediate-early manner. LRE consists of two motifs, TCAYR,
      which is an AP-1 half site with two flanking bases, and (A/T)
      (G/C)NTTYC(A/T)NTTY, which resembles in part the interferon-stimulated responsive
      element (ISRE). The orientation of these two motifs relative to each other in
      MuRantes differed from that in crg-2. These two motifs are separated by 10 and 6
      nonconsensus nucleotides in the MuRantes and crg-2 LREs, respectively.
      Stimulation of macrophage-like RAW 264.7 cells with alpha/beta interferon did not
      activate MuRantes, indicating that the ISRE-like motif in MuRantes does not have
      ISRE activity. Upon stimulation of RAW 264.7 cells with LPS, proteins capable of
      binding to LRE accumulate in the nuclei as measured by electrophoretic mobility
      shift assay. These LRE-binding proteins include c-Jun and CREB.

PMID- 7513048
TI  - In vitro study of processing of the intron-encoded U16 small nucleolar RNA in
      Xenopus laevis.
AB  - It was recently shown that a new class of small nuclear RNAs is encoded in
      introns of protein-coding genes and that they originate by processing of the pre
      mRNA in which they are contained. Little is known about the mechanism and the
      factors involved in this new type of processing. The L1 ribosomal protein gene of
      Xenopus laevis is a well-suited system for studying this phenomenon: several
      different introns encode for two small nucleolar RNAs (snoRNAs; U16 and U18). In
      this paper, we analyzed the in vitro processing of these snoRNAs and showed that
      both are released from the pre-mRNA by a common mechanism: endonucleolytic
      cleavages convert the pre-mRNA into a precursor snoRNA with 5' and 3' trailer
      sequences. Subsequently, trimming converts the pre-snoRNAs into mature molecules.
      Oocyte and HeLa nuclear extracts are able to process X. laevis and human
      substrates in a similar manner, indicating that the processing of this class of
      snoRNAs relies on a common and evolutionarily conserved mechanism. In addition,
      we found that the cleavage activity is strongly enhanced in the presence of Mn2+
      ions.

PMID- 7513047
TI  - Cloning and characterization of a novel RNA involved in cellular growth
      regulation.
AB  - During the course of antisense oligodeoxynucleotide (oligo) inhibition
      experiments investigating the role of insulin-like growth factor I (IGF-I) in the
      WI-38 cell cycle, we found that a sense-strand oligo (S oligo), used as a
      control, inhibited DNA synthesis 90 to 95%. S1 nuclease protection assays
      demonstrated that this S oligo formed intracellular duplexes with WI-38 RNA, and
      Northern (RNA) hybridization analyses demonstrated specific hybridization of this
      32P-labeled S oligo to 1.8-, 2.3-, and 3.2-kb RNAs. We have cloned and sequenced
      a 2,251-bp cDNA, designated BB1, corresponding to the 2.3-kb RNA. Decoding of the
      BB1 cDNA sequence reveals several open reading frames arranged in a motif similar
      to that seen in proteins subject to translational control mechanisms. Homology
      searches of nucleic acid and protein data bases reveal no significant homology of
      BB1 with known sequences other than a 234-bp region in the BB1 5' untranslated
      region that shared 97% homology with a region in the 3' untranslated region of
      the human cdc42 mRNA. S1 nuclease protection analyses performed with IGF-I gene
      fragments and computer homology searches demonstrated that the BB1 RNA does not
      derive from transcription from the opposite strand of the IGF-I gene. Northern
      hybridization analyses of RNA extracted from serum-starved HeLa S3 cells
      demonstrated that steady-state BB1 RNA levels increased upon serum growth
      stimulation, with steady-state levels peaking 4 h after release from the block
      induced by serum starvation. Antisense oligo inhibition experiments using
      specific BB1 antisense oligos targeted to the putative open reading frames of the
      BB1 RNA reduce DNA synthesis of HeLa S3 cells to 15% of control levels,
      indicating that the BB1 RNA is essential for cell cycle traversal and, as such,
      encodes a growth-reguLating gene product.

PMID- 7513049
TI  - Activation of the glycoprotein hormone alpha-subunit promoter by a LIM
      homeodomain transcription factor.
AB  - Recently, a pituitary-specific enhancer was identified within the 5' flanking
      region of the mouse glycoprotein hormone alpha-subunit gene. This enhancer is
      active in pituitary cells of the gonadotrope and thyrotrope lineages and has been
      designated the pituitary glycoprotein hormone basal element (PGBE). In the
      present studies, we sought to isolate and characterize proteins which interact
      with the PGBE. Mutagenesis experiments identified a 14-bp imperfect palindrome
      that is required for binding of a factor which is present in cells of gonadotrope
      and thyrotrope lineages but not in other cells. Screening of a mouse cDNA library
      with a DNA probe containing the imperfect palindrome resulted in the isolation of
      a LIM-homeodomain transcription factor. The cDNA predicts a mouse protein which
      is 94% identical to the recently described rat LIM-homeodomain protein LH-2. LH-2
      contains two zinc fingers (LIM domain) and a consensus homeodomain. Hybridization
      analysis revealed relatively high expression of LH-2 mRNA in the central nervous
      system and in pituitary cells of the gonadotrope and thyrotrope lineages. Lower
      or nondetectable levels of LH-2 mRNA were found in other pituitary cells and
      tissues, including placental cells. Recombinant LH-2 homeodomain was found to
      selectively bind to the previously identified imperfect palindrome in the PGBE.
      Point mutations in the PGBE resulted in parallel losses in the binding of a
      nuclear factor from a cell line of the gonadotrope lineage and recombinant LH-2
      binding activity. Use of an antibody to LH-2 provided evidence that endogenous
      PGBE-binding activity from cells of the gonadotrope lineage involves a protein
      which is immunologically related to LH-2. Expression of LH-2 in two heterologous
      cell types resulted in activation of a reporter gene containing the mouse alpha
      promoter. These data suggest that the LIM-homeodomain factor LH-2 plays a role in
      stimulating tissue-specific expression of the mouse glycoprotein hormone alpha
      subunit. The finding that a LIM-homeodomain protein can stimulate expression of
      one of the earliest markers of pituitary differentiation raises the possibility
      that this factor plays a role in cell lineage determination in the pituitary.

PMID- 7513053
TI  - One-sided invasion events in homologous recombination at double-strand breaks.
AB  - Two classes of homologous recombination mechanism for repair of double-strand
      breaks (DSBs) have been described in eukaryotes so far. One is conservative and
      has been explained by the double-strand break repair model (Szostak et al.,
      1983), whereas the other one is non-conservative and has been explained by the
      single-strand annealing model (Lin et al., 1984). Here, we will review data
      supporting the existence of another homologous recombination mechanism for double
      strand break repair. We will present the one-sided invasion model that we have
      proposed to explain this mechanism and discuss its potential implication in
      various homologous recombination events.

PMID- 7513054
TI  - The E. coli recA gene can restore the defect in mutagenesis of the pso4-1 mutant
      of S. cerevisiae.
AB  - The E. coli recA gene was introduced into the pso4-1 mutant of S. cerevisiae and
      transformants were treated with 8-MOP+UVA and 254-nm UV light. The results showed
      that the recA gene increased the resistance to the toxic effect of 8-MOP+UVA and
      restored the frequency of reversion of the pso4-1 mutants after both treatments.
      The presence of the recA gene stimulated expression of the small subunit of the
      ribonucleotide reductase (Rnr2) in the pso4-1 mutants. Thus the E. coli recA gene
      is functional in yeast. Moreover, it was shown that the pso4-1 mutant is
      epistatic to pso1-1 and rad6-1, which belong to a mutagenic repair pathway. We
      propose here that the PSO4 gene has some role in the control of mutagenic repair
      in yeast.

PMID- 7513051
TI  - Imprecise excision of the Caenorhabditis elegans transposon Tc1 creates
      functional 5' splice sites.
AB  - Imprecise excision of the Caenorhabditis elegans transposon Tc1 from a specific
      site of insertion within the unc-54 myosin heavy chain gene generates either wild
      type or partial phenotypic revertants. Wild-type revertants and one class of
      partial revertants contain insertions of four nucleotides in the unc-54 third
      exon (Tc1 "footprints"). Such revertants express large amounts of functional unc
      54 myosin despite having what would appear to be frameshifting insertions in the
      unc-54 third exon. We demonstrate that these Tc1 footprints act as efficient 5'
      splice sites for removal of the unc-54 third intron. Splicing of these new 5'
      splice sites to the normal third intron splice acceptor removes the Tc1 footprint
      from the mature mRNA and restores the normal translational reading frame. Partial
      revertant unc-54(r661), which contains a single nucleotide substitution relative
      to the wild-type gene, is spliced similarly, except that the use of its new 5'
      splice site creates a frameshift in the mature mRNA rather than removing one. In
      all of these revertants, two alternative 5' splice sites are available to remove
      intron 3. We determined the relative efficiency with which each alternative 5'
      splice site is used by stabilizing frameshifted mRNAs with smg(-) genetic
      backgrounds. In all cases, the upstream member of the two alternative sites is
      used preferentially (> 75% utilization). This may reflect an inherent preference
      of the splicing machinery for the upstream member of two closely spaced 5' splice
      sites. Creation of new 5' splice sites may be a general characteristic of Tc1
      insertion and excision events.

PMID- 7513052
TI  - Cloning, characterization, and expression of a novel GDP dissociation inhibitor
      isoform from skeletal muscle.
AB  - Cellular mechanisms for controlling membrane trafficking appear to involve small
      GTP-binding proteins such as the Rab proteins. Rab function is regulated by GDP
      dissociation inhibitor (GDI), which releases Rab proteins from membranes and
      inhibits GDP dissociation. Here we report the isolation of a full-length cDNA
      encoding a novel GDI isoform of 445 amino acids (GDI-2) with a deduced molecular
      weight of 50,649 from mouse skeletal muscle. Full-length and partial cDNA clones
      encoding a previously reported GDI protein (GDI-1) were also isolated from cDNA
      libraries prepared from rat brain and mouse skeletal muscle, respectively. The
      degree of deduced amino acid sequence identity between mouse GDI-2 and our mouse
      GDI-1 cDNA clone is 86%. Northern (RNA blot) analysis revealed that in human
      tissues, both GDI-1 and GDI-2 transcripts were abundant in brain, skeletal
      muscle, and pancreas but were weakly expressed in heart and liver. GDI-1 mRNA was
      expressed in kidney, whereas GDI-2 was almost absent, while in lung the relative
      amounts of these mRNA species were reversed. Specific antibodies against mouse
      GDI-1 and GDI-2 based on unique peptide sequences in the proteins were raised.
      Differentiation of 3T3-L1 fibroblasts into highly insulin-responsive adipocytes
      was accompanied by large increases in both mRNA and protein levels of GDI-1 and
      GDI-2. GDI-1 and GDI-2 expressed as glutathione S-transferase fusion proteins
      were both able to solubilize the membrane-bound forms of Rab4 and Rab5 in a
      GDP/GTP-dependent manner. Taken together, these data demonstrate that the protein
      products of at least two genes regulate the membrane dynamics of Rab proteins in
      mice.

PMID- 7513056
TI  - A new UV-sensitive syndrome not belonging to any complementation groups of
      xeroderma pigmentosum or Cockayne syndrome: siblings showing biochemical
      characteristics of Cockayne syndrome without typical clinical manifestations.
AB  - We report here on two siblings who show no clinical manifestations except for
      slight cutaneous photosensitivity and cutaneous pigmentation but have biochemical
      characteristics of Cockayne syndrome (CS). Fibroblasts derived from the patients
      (Kps2 and Kps3) were 3-4 times more sensitive to UV than normal cells. Although
      unscheduled DNA synthesis (UDS) in these cells was at a normal level, recovery of
      RNA synthesis (RRS) after UV irradiation was severely depressed. Microinjection
      of bacteriophage T4 endonuclease V into the cells corrected RRS after UV
      irradiation to a level near normal. These results indicate that DNA repair of
      cyclobutane-type pyrimidine dimers is impaired in the cells and the biochemical
      characteristics are similar to those of CS cells. However, cell fusion
      complementation tests with CS group A and B cells resulted in correction of RRS
      after UV irradiation. Cell fusion with XP group A, B, D, F and G cells also
      corrected RRS after UV irradiation, and microinjection of cell extracts prepared
      from Kps3 cells corrected UDS in XP group C and E cells, indicating that the
      patients do not belong to any complementation group of XP or CS. These results
      suggest that the patients have a new UV-sensitive syndrome with a biochemical
      phenotype of CS.

PMID- 7513058
TI  - Isolation and preliminary characterisation of an X-ray-sensitive mammalian mutant
      cell line (WMXRS-1).
AB  - Mammalian cell lines that are sensitive to particular genotoxic agents have
      proved the most effective starting point for the cloning of human DNA-repair
      genes. After ethyl methanesulphonate mutagenesis of the parent murine fibroblast
      L-cell line, a new mammalian X-ray-sensitive cell line (WMXRS-1) was isolated.
      For selection of the mutant, a novel detection method was used: putative X-ray
      sensitive clones were identified by their lack of incorporation of the DNA
      precursor, bromodeoxyuridine, after irradiation. The WMXRS-1 cell line was
      collaterally sensitive to ultraviolet radiation and some other agents known to be
      removed from DNA by the nucleotide excision repair pathway, but not to bleomycin
      or hydrogen peroxide. In relation to the wild-type strain, WMXRS-1 showed a
      similar pattern of induction of micronuclei up to an X-ray dose of 4 Gray and a
      similar DNA double-strand break (dsb) induction profile. The overall level of dsb
      rejoining was the same in the parent and mutant lines. However, WMXRS-1
      demonstrated a reduced initial rate of dsb-rejoining, perhaps accounting for its
      radiosensitivity. WMXRS-1 also showed a greater G2 cell cycle phase accumulation
      after treatment with mitomycin-C. The cross-sensitivity profile and strand-break
      rejoining deficiency phenotype of WMXRS-1 is unique amongst previously
      characterised mammalian mutant cell lines.

PMID- 7513057
TI  - Increased sensitivity to DNA-alkylating agents in CHO mutants with decreased
      poly(ADP-ribose) polymerase activity.
AB  - Using a replica-plating procedure and a 32P-NAD+ permeable cell-screening assay,
      we have isolated a CHO mutant, PADR-9, which displays approximately 17% of the
      wild-type level of poly(ADP-ribose) polymerase activity. Biochemical analysis of
      the mutant using activity, Western, and Northern blot techniques indicate that
      relative to its parent cell, the mutant's enzyme activity, antibody recognition,
      and mRNA levels have been reduced to approximately the same extent. These results
      are consistent with a mutation in the PADR-9 cell which has resulted in a
      reduction in enzyme synthesis due to reduced mRNA synthesis and/or stability.
      Relative to wild-type CHO cells, the PADR-9 mutant has increased sensitivity to
      killing by DNA-alkylating agents but has normal gamma-ray sensitivity.
      Correlation between a decrease in poly(ADP-ribose) polymerase activity and an
      increased sensitivity to DNA-alkylating agents suggests that poly(ADP-ribose)
      synthesis may be important in the repair and/or induction of DNA damage produced
      by these agents.

PMID- 7513055
TI  - Gene-specific DNA repair of UV-induced cyclobutane pyrimidine dimers in some
      cancer-prone and premature-aging human syndromes.
AB  - We have examined the gene-specific DNA repair of UV-induced cyclobutane
      pyrimidine dimers (CPDs) in fibroblasts from the following cancer prone
      syndromes: familial dysplastic nevus syndrome (DNS), Gardner's syndrome (GS), and
      Bloom's syndrome (BS). These heritable human syndromes are associated with DNA
      damage hypersensitivity and have been considered as potentially DNA repair
      deficient. Previous determinations of DNA repair in these cell strains have been
      done solely at the level of the overall genome. That approach is not sensitive
      enough to detect deficiencies in repair at the level of the gene. Defective
      preferential repair of active genes may impair survival and affect genomic
      stability. This is exemplified by the disorder Cockayne's syndrome (CS) which is
      associated with a selective deficiency in the preferential repair of active
      genes. In this study, we have used a Cockayne's syndrome cell strain and also a
      normal human fibroblast cell line as a control. Repair was studied in the
      transcriptionally active gene dihydrofolate reductase (DHFR), the inactive delta
      globin gene, and in the c-myc protooncogene. In the DNS, GS and BS cell lines, we
      find preferential repair similar to that in normal cells. In Cockayne's syndrome
      cells, there is no preferential repair of the DHFR gene.

PMID- 7513059
TI  - Roles of transcription and repair in alkylation mutagenesis.
AB  - Mutations occurring in Escherichia coli cells exposed to alkylating agents have
      been analyzed using an assay for forward mutations in the E. coli rpsL gene
      cloned on a high copy number plasmid. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      induced mutations were recovered from wild-type and O6-methylguanine
      methyltransferase-deficient mutant (ada- ogt-) cells and their sequence
      alterations determined. We found that the mutations recovered from the wild-type
      strain were predominantly G:C to A:T transitions located at several hot spots in
      the rpsL sequence. A vast majority of the mutations were found at guanine
      residues preceded by thymine on the transcribed strand of the target gene.
      Although the methyltransferase mutant showed hypersensitivity to the alkylating
      reagent in terms of mutagenic effect and cell killing effects, the class and site
      distributions of the rpsL- mutations recovered from MNNG-treated ada- ogt- cells
      were similar to those observed with MNNG-treated wild-type cells. Therefore, the
      site preference of MNNG-induced rpsL- mutations seems to be due not to the
      specificity of methyl-transferring repair enzymes but probably to the
      distribution of the mutagenic lesions (O6-methylguanine) in the target sequence.
      Mutations induced by methyl methanesulfonate, an SN2 alkylating agent, showed
      similar class and site distributions in the rpsL system. The site preference of
      MNNG-induced mutations was significantly changed when the level of transcription
      of the rpsL gene was decreased to 120-fold lower than that promoted by the
      authentic rpsL promoter. Under these conditions, 78% of mutations were induced at
      the central guanine of 5'-GG(A or C)-3' and 2/3 of them were on the non
      transcribed strand of the rpsL gene. These results suggested that the site
      preference of MNNG-induced mutations is determined by at least three factors: (i)
      a flanking-base effect on the chemical reactivity of a guanine residue, (ii)
      transcribed strand-specific repair, probably by the UvrABC system, and (iii) the
      effects of transcription of the target gene on the alkylation of DNA and the
      strand-specific repair.

PMID- 7513050
TI  - A novel mammalian protein, p55CDC, present in dividing cells is associated with
      protein kinase activity and has homology to the Saccharomyces cerevisiae cell
      division cycle proteins Cdc20 and Cdc4.
AB  - A novel protein, p55CDC, has been identified in cycling mammalian cells. This
      transcript is readily detectable in all exponentially growing cell lines but
      disappears when cells are chemically induced to fall out of the cell cycle and
      differentiate. The p55CDC protein appears to be essential for cell division,
      since transfection of antisense p55CDC cDNA into CHO cells resulted in isolation
      of only those cells which exhibited a compensatory increase in p55CDC transcripts
      in the sense orientation. Immunoprecipitation of p55CDC yielded protein complexes
      with kinase activity which fluctuated during the cell cycle. Since p55CDC does
      not have the conserved protein kinase domains, this activity must be due to one
      or more of the associated proteins in the immune complex. The highest levels of
      protein kinase activity were seen with alpha-casein and myelin basic protein as
      substrates and demonstrated a pattern of activity distinct from that described
      for the known cyclin-dependent cell division kinases. The p55CDC protein was also
      phosphorylated in dividing cells. The amino acid sequence of p55CDC contains
      seven repeats homologous to the beta subunit of G proteins, and the highest
      degree of homology in these repeats was found with the Saccharomyces cerevisiae
      Cdc20 and Cdc4 proteins, which have been proposed to be involved in the formation
      of a functional bipolar mitotic spindle in yeast cells. The G beta repeat has
      been postulated to mediate protein-protein interactions and, in p55CDC, may
      modulate its association with a unique cell cycle protein kinase. These findings
      suggest that p55CDC is a component of the mammalian cell cycle mechanism.

PMID- 7513060
TI  - Endonuclease VII of phage T4 nicks N-2-acetylaminofluorene-induced DNA structures
      in vitro.
AB  - We have tested in vitro the activity of T4 endonuclease VII on three different
      double-stranded oligonucleotides bearing a single N-2-acetylaminofluorene (AAF)
      adduct covalently bound to each of the three guanine residues located within the
      NarI site (G1G2CG3CC), a strong frameshift mutation hot spot in E. coli. With the
      oligonucleotides modified at G2 and G3 a specific cleavage pattern with T4
      endonuclease VII was observed in the complementary strand while no cleavage was
      found in the adduct-bearing strand. On the other hand, when G1 was modified, only
      a very faint cleavage band was observed (< 1%). These differences in nicking
      among the three AAF-modified DNA substrates are discussed in terms of the
      polymorphic nature in adduct-induced DNA structures as previously shown. This
      "non-physiological" activity of a DNA resolvase is discussed in terms of a
      potential role for such enzymes in the induction of frameshift mutations.

PMID- 7513061
TI  - Acrolein genotoxicity in Drosophila melanogaster. III. Effects of metabolism
      modification.
AB  - In order to investigate the role of metabolism in acrolein genotoxicity in D.
      melanogaster, the action of several metabolism modifiers, namely phenobarbital,
      an inducer of xenobiotic metabolism, phenylimidazole and iproniazid, inhibitors
      of oxidative activities of cytochrome P450, and diethyl maleate, a glutathione
      depleting agent, have been assayed using the sex-linked recessive lethal (SLRL)
      test, with two different administration routes (feeding and injection). The
      results support the hypothesis that acrolein is not only a direct mutagen but is
      also transformed, by oxidative activities of cytochrome P450 after glutathione
      conjugation, into an active metabolite, possibly glycidaldehyde. Moreover,
      acrolein is deactivated by an enzymatic activity induced by phenobarbital.

PMID- 7513062
TI  - Induction of adaptive response by nitrofurantoin against oxidative DNA damage in
      some bacterial cells.
AB  - Pretreatment with a sublethal dose of nitrofurantoin did not give any protection
      to Vibrio cholerae OGAWA 154 (wild-type) cells against subsequent treatment with
      challenging doses of MNNG and vice versa. However, pretreatment with a sublethal
      dose of nitrofurantoin offered significant protection to the bacterial cells
      against subsequent treatment with challenging doses of H2O2 and vice versa.
      Further, sublethal doses of nitrofurantoin or H2O2 produced almost the same
      degree of protection against challenges by H2O2 or nitrofurantoin. Both the
      alkylating agent MNNG and the oxidative agent H2O2 induced adaptive responses in
      Vibrio cholerae OGAWA 154 cells against subsequent challenge by the respective
      agents. The experiments presented in this communication revealed that
      nitrofurantoin produced an adaptive response in bacterial cells against oxidative
      and not alkylating DNA damage.

PMID- 7513063
TI  - In vitro micronucleus induction by polymethyl methacrylate bone cement in
      cultured human lymphocytes.
AB  - Human lymphocytes cultured in vitro were used to assess the ability of polymethyl
      methacrylate (PMMA), currently used in orthopaedic surgery as bone cement, to
      induce micronuclei in binucleated cells. The results of the study show a
      significant increase in the micronucleus frequency in treated cultures and
      therefore the genotoxic effect of PMMA bone cement or its ingredients (methyl
      methacrylate, dimethyl para-toluidine and hydroquinone) usually present in self
      curing methacrylate bone cement and released in small quantities after
      polymerisation. This effect is evident during the stage immediately after the
      polymerisation process, and after a certain period of time (5 days in our
      experimental model).

PMID- 7513066
TI  - Cytotoxic and genetic effects of X-irradiation of human cells in the presence of
      chlorpromazine.
AB  - Human epidermoid carcinoma cells (Hep-2) were X-irradiated in the presence of 5
      10 micrograms/ml of chlorpromazine (CPZ). Survival of the cells decreased with
      increasing CPZ concentration. Lymphocytes from three normal volunteers exposed to
      X-irradiation in the presence of CPZ showed an increased frequency of dicentric
      and ring formation.

PMID- 7513065
TI  - Effects of lymphocyte subpopulations on the clonal assay of HPRT mutants:
      occupational exposure to cytostatic drugs.
AB  - The mutagenic effect of occupational exposure to antineoplastic agents was
      studied in chemotherapy nurses and pharmacists using the T-lymphocyte clonal
      assay. A significant increase in mutant frequency was observed compared to
      controls. However, in the present study, cloning efficiency without selection
      (CEU) was significantly reduced in exposed personnel raising the possibility of
      an overestimation of the calculated MF. Changes in lymphocyte populations and
      clonal potential of T-cells were also observed following exposure. CEU was
      related to % CD4 cells but CE with selection (CETG) was not. Differences in
      clonal ability of T-cells under selective and unselective conditions coupled with
      differential lethal effect of antineoplastic agents on lymphocyte subsets may
      result in inaccurate estimation of MF.

PMID- 7513064
TI  - Evaluation of the genotoxic potential of the alkaloid boldine in mammalian cell
      systems in vitro and in vivo.
AB  - Boldine is an alkaloid present in Peumus boldus (popularly called "boldo-do
      chile" in Brazil) which has healing properties and is used for the treatment of
      gastrointestinal disorders. The possible clastogenic effect of the drug was
      tested in vitro on human peripheral blood lymphocytes by evaluating the induction
      of chromosome aberrations and sister-chromatid exchanges (SCEs). Cultures from
      different individuals were treated with boldine at concentrations of 10, 20 and
      40 micrograms/ml of culture medium. The effect of the alkaloid was also tested in
      an in vivo assay using BALB/c mouse bone marrow cells. Boldine was administered
      to the animals by gavage at the concentrations of 225, 450 and 900 mg/kg body
      weight. Under the conditions used, boldine did not induce a statistically
      significant increase in the frequency of chromosome aberrations or SCEs in either
      test system.

PMID- 7513068
TI  - Cigarette smoking protects mononuclear blood cells of carcinogen exposed workers
      from additional work exposure-induced DNA single strand breaks.
AB  - DNA single-strand breaks in mononuclear blood cells (MNC) of taxi drivers,
      painters, ethylene oxide-exposed sterilization workers, metal workers, and car
      mechanics were detected by alkaline filter elution and compared to smoking and
      non-smoking control persons. Cigarette smoking caused a small but statistically
      significant increase in control persons (13.5%). In all occupationally exposed
      groups except the car mechanics, statistically significant increases of DNA
      single-strand breaks were detected in non-smokers compared to non-smoking
      controls or comparing groups with high and low exposure. For non-smoking workers
      the increase in DNA single-strand breaks was found to be 22% for taxi drivers,
      60% for painters, 70% for ethylene oxide-exposed workers, and 69% for metal
      workers compared to control persons. For smokers, however, the increase in DNA
      single-strand breaks caused by additional occupational exposure was smaller and
      did not reach statistical significance in any of the occupational groups
      investigated in this study. Since a high level of glutathione may help to
      detoxify electrophilic DNA-damaging agents we measured the concentration of total
      glutathione in MNC of smoking and non-smoking control persons. The glutathione
      concentration was 13% higher in smokers, but statistical significance was weak (p
      < 0.05; t-test). Thus cigarette smoking, which represents a highly significant
      risk factor in carcinogenesis by itself, protects on the other hand against some
      additional genotoxic insults.

PMID- 7513067
TI  - Genotoxic and mutagenic effects of guarana (Paullinia cupana) in prokaryotic
      organisms.
AB  - Aqueous extracts of Paullinia cupana (guarana), a species that belongs to the
      Sapindaceae family, were analyzed for the presence of genotoxic activities in
      bacterial cells. The extracts of guarana were genotoxic as assessed by lysogenic
      induction in Escherichia coli and they were also able to induce mutagenesis in
      Salmonella typhimurium. Addition of S9 microsomal fraction, catalase, superoxide
      dismutase or thiourea counteracted the genotoxic activity of guarana, suggesting
      that oxygen reactive species play an essential role in the genotoxicity of
      aqueous guarana extracts. The genotoxic activity in the extracts was related to
      the presence of a molecular complex formed by caffeine and a flavonoid (catechin
      or epicatechin) in the presence of potassium.

PMID- 7513069
TI  - [A case of demyelinating disease difficult for classification].
AB  - A case of difficult for classification demyelinating disease of diffuse
      (transitional) type is presented. The described case seems to testify about the
      identity of hyperergic (para-infections) encephalomyelitis and acute multiple
      sclerosis of diffuse type.

PMID- 7513072
TI  - Amygdala kindling in immature rats: proconvulsant effect of the organophosphate
      insecticide-chlorpyrifos.
AB  - Administration of the organophosphate insecticide, chlorpyrifos to immature rats
      exerted a proconvulsant effect on seizures induced by kindling. Chlorpyrifos was
      administered to 16 or 17 day old rats in a dose range of 0.3 to 10 mg/kg,
      subcutaneously. Amygdala kindling was performed by stimulating the rats every 15
      minutes to a total of 20 stimulations. Kindling occurred more rapidly in the
      chlorpyrifos treated rats than vehicle treated rats, the proconvulsant effect was
      dose-dependent. The proconvulsant effect of chlorpyrifos was more pronounced in
      the early stages of kindling, indicating a possible increase in local
      excitability of the amygdala in the presence of chlorpyrifos. Chlorpyrifos also
      reduced the after discharge threshold in the amygdala in a dose-dependent manner
      and increased the duration of after discharges elicited by electrical stimulus,
      indicating an increase in excitability of the amygdala. The effects of
      chlorpyrifos on kindling were additive with xylene: the proconvulsant effect in
      the early stages of kindling was greatly enhanced by xylene. Xylene, administered
      alone as a 0.2% solution, reduced the after discharge threshold of the amygdala,
      increased the after discharge duration and increased the rate of kindling. These
      experiments demonstrate a proconvulsant effect of chlorpyrifos in amygdala
      kindling and this proconvulsant action is additive with xylene.

PMID- 7513070
TI  - Expression of cytokines in brain lesions in subacute sclerosing panencephalitis.
AB  - We analyzed frozen brain specimens from three patients with subacute sclerosing
      panencephalitis (SSPE) for the presence of interleukin (IL)-1 beta, IL-2, IL-6,
      tumor necrosis factor (TNF), lymphotoxin (LT), and interferon (IFN)-gamma using
      immunocytochemical techniques. We detected these cytokines in SSPE brain lesions
      demonstrating extensive cellular infiltrates, demyelination, and gliosis. Double
      label immunocytochemistry, using cell-specific markers, showed that positive
      immunoreactivity for these cytokines was present on both infiltrating cells and
      resident brain cells. We also found IL-6, TNF, and IFN-gamma at lower levels in
      brain tissue from a patient with progressive multifocal leukoencephalopathy. In
      contrast, normal control brain sections showed no reactivity for any of the
      cytokines. These findings indicate that IL-1 beta, IL-2, IL-6, TNT, LT, and IFN
      gamma may be produced in SSPE lesions and may be involved in the lesion
      pathogenesis of SSPE.

PMID- 7513073
TI  - Effects of gamma and delta hexachlorocyclohexane isomers on inositol phosphate
      formation in cerebral cortex and hippocampus slices from developing and adult
      rat.
AB  - Hexachlorocyclohexane (HCH) isomers, mainly gamma-HCH (insecticide with stimulant
      and convulsant effects in man) and delta-HCH (neurodepressant agent), are known
      to inhibit the synthesis of phosphatidylinositol (PI) in diverse cell systems,
      but action on phosphoinositide hydrolysis has been scarcely studied. The present
      work examines the effects of gamma-HCH and delta-HCH on the accumulation of
      [3H]inositol phosphates (InsP) from the hydrolysis of prelabelled
      phosphoinositides, in cerebral cortical and hippocampal slices from developing (8
      day-old) and adult rats. In developing and adult animals both isomers increased
      InsP formation in a concentration-related manner. delta-HCH was statistically
      more potent in developing than in adult animals (maximum effects obtained were
      280% and 200% of basal InsP accumulation at 300 microM, respectively). gamma-HCH
      showed lower stimulation (maximal effect was 170% at 300 microM, at both ages)
      than delta isomer. No differences between brain regions were observed after
      treatment with HCH isomers. Effects of HCH isomers (200 microM) on
      phosphoinositide hydrolysis stimulation by glutamate, carbachol and noradrenaline
      were selective for the transmitter receptor agonist and age studied. delta-HCH
      inhibited glutamate and carbachol stimulation in cerebral cortex from developing
      animals and did not modify it in adults. Combination of delta-HCH and
      noradrenaline increased the effects of this neurotransmitter in immature rats,
      while only noradrenaline stimulation was observed in adult rats. A noticeable
      effect of gamma-HCH was that it did not increase glutamate and carbachol
      stimulation in cerebral cortex of developing rats.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7513074
TI  - Lead in petrol and blood lead levels.

PMID- 7513071
TI  - Organ-specific autoantigens induce interferon-gamma and interleukin-4 mRNA
      expression in mononuclear cells in multiple sclerosis and myasthenia gravis.
AB  - T cells recognizing the myelin components myelin basic protein (MBP) and
      proteolipid protein (PLP) are increased in multiple sclerosis (MS), and there are
      elevated numbers of T cells recognizing the nicotinic acetylcholine receptor
      (AChR) in myasthenia gravis (MG). However, the cytokine repertoires in these
      diseases are largely unknown. We adopted in situ hybridization with radiolabeled
      complementary DNA oligonucleotide probes to enumerate mononuclear cells that
      expressed the T-helper type 1 (Th1) cell-related interferon-gamma (IFN-gamma) and
      Th2-associated interleukin-4 (IL-4) after short-term culture in the presence of
      autoantigen. High numbers of IFN-gamma and IL-4 mRNA-expressing cells in response
      to MBP and PLP were detected in patients with untreated MS, and to AChR in MG.
      The levels of IFN-gamma and IL-4 mRNA-positive cells in MS after culture in the
      presence of AChR, and in MG after culture in the presence of MBP or PLP, did not
      differ from those detected after culture without antigen. The CSF of MS patients
      contained four- to eightfold more myelin protein-reactive IFN-gamma and IL-4
      expressing cells. The findings imply that MS and MG are associated with mixed Th1
      and Th2-like cell responses directed to organ-specific target antigens.

PMID- 7513075
TI  - The availability of granulocyte colony stimulating factor.

PMID- 7513076
TI  - Immunohistological examination of the relationship between metastatic potential
      and expression of adhesion molecules and 'selectins' on melanoma cells.
AB  - Identification of antigens by monoclonal antibodies (MAbs) on sections of human
      melanoma by immunoperoxidase techniques was used to determine whether certain
      adhesion molecules and "selectin-like" molecules may be related to the metastatic
      potential of primary melanoma. The adhesion molecules examined were the leukocyte
      function antigen (LFA-1) and its ligand--intercellular adhesion molecule-1 (ICAM
      1), the receptor alpha V beta 3 for vitronectin, its subunits alpha V and beta 3,
      and the CD36 receptor for thrombospondin (TSP). The criteria used to establish
      metastatic potential were relation of the molecules to tumor thickness and
      differences in expression: (i) between radial and vertical growth phases of the
      primary tumors and (ii) between 34 primary and 21 unrelated metastases. By these
      criteria ICAM-1, alpha V beta 3 and its subunit were associated with the
      malignant potential of primary melanoma. These molecules were not expressed on
      nevi or other skin cancers with low metastatic potential such as squamous (SCC)
      and basal cell carcinomas (BCC). In contrast, expression of TSP and the CD36
      receptor for TSP were not related to metastatic potential. CD36 was expressed
      widely not only on melanoma but also on BCC, SCC and nevi. Similarly, the
      selectin-like molecule, CD44, was widely expressed on melanoma and non-melanoma
      carcinomas. The lymph node homing receptor, Leu 8, and the cutaneous lymphocyte
      antigen (CLA) were not detected on melanoma. Leu 8 was present on normal
      epithelium and SCCs, and common leucocyte antigen (CLA) was detected on
      lymphocytes in the epithelium and near melanoma. These results support previous
      suggestions that expression of ICAM-1 and V beta 3 integrin or its subunit beta 3
      on melanoma may be a useful prognostic marker in primary melanoma. They do not
      support a role for CD44, Leu 8, CLA and TSP or its receptor CD36 in the
      metastatic process in melanoma.

PMID- 7513077
TI  - Granulocyte and granulocyte-macrophage colony-stimulating factors in cord and
      maternal serum at delivery.
AB  - Impaired neutrophil responses contribute to the neonate's increased
      susceptibility to infection. Because granulocyte colony-stimulating factor (G
      CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhance
      granulocyte and macrophage number and function, their use in the management of
      neonatal sepsis may be beneficial. Little is known about the endogenous levels of
      G-CSF and GM-CSF. In adults, raised values for G-CSF, but not GM-CSF, have been
      demonstrated in patients with infection, and conflicting data has emerged
      regarding CSF levels in neonates. We have used an ELISA to measure maternal and
      cord serum G-CSF and GM-CSF at the time of delivery, with gestational age between
      25 and 42 wk. In mothers, an inverse linear relationship between gestational age
      and GM-CSF levels (p = 0.049) was found, but no association with G-CSF levels was
      observed. In neonates, a quadratic association was found between GM-CSF levels
      and gestational age (p = 0.019), whereas G-CSF levels showed an inverse linear
      association (p = 0.015). In addition, an association was found between maternal
      and cord GM-CSF (p = 0.007) but not G-CSF levels in paired samples. The effect of
      gestational age on the cytokine levels could not be explained by the white cell
      count, the absolute neutrophil count, pregnancy-induced hypertension, or the
      presence of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513079
TI  - Growth hormone bioactivity in girls with Turner's syndrome: correlation with
      insulin-like growth factor I.
AB  - We have recently developed a new bioassay for growth hormone (GH) in serum, which
      is based on the ability of GH to suppress glucose use in cultured murine
      adipocytes. We tested the hypothesis that bioactive GH (B-GH) concentrations
      would correlate better with the GH-dependent peptides, IGF-I, and IGF-binding
      protein-3 (IGFBP-3) than would GH determined by conventional RIA (RIA-GH). Twenty
      five girls with Turner's syndrome were studied. The subjects had ages ranging
      from 4.8 to 15.9 y and height SD from the mean (SD score) ranging from -0.77 to 
      5.67. Blood samples were obtained every 15 or 20 min for 12 h overnight. For each
      girl, an equal aliquot of each overnight sample was pooled for determination of B
      GH, RIA-GH, IGF-I, IGFBP-3, LH, FSH, and estradiol. Measurable estradiol
      concentrations were present in six girls and were sufficient to suppress
      gonadotropin concentrations in two girls, but they did not alter B-GH, RIA-GH,
      IGF-I, and IGFBP-3 concentrations compared with the age-matched girls without
      measurable estradiol concentrations. Hence, data for all girls were combined for
      subsequent regression analyses. RIA-GH did not correlate significantly with B-GH,
      IGF-I, or IGFBP-3. B-GH exhibited a significant correlation with IGF-I (r =
      0.407, p < 0.05), and the correlation with IGFBP-3 was better than that for RIA
      GH (r = 0.355 versus 0.064, B-GH and RIA-GH, respectively). None of the B-GH, RIA
      GH, IGF-I, or IGFBP-3 concentrations had a significant correlation with height SD
      score or height velocity SD score.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513078
TI  - Serum levels of oncofetal markers CA 125, CA 19-9, and alpha-fetoprotein in
      children with hereditary tyrosinemia type I.
AB  - Hereditary tyrosinemia type I (HTT-I) is an inherited metabolic disorder with
      severe liver disease and a high risk for hepatic malignancy. Patients with HTT-I
      are monitored with repeated analyses of serum amino acids, urine succinylacetone,
      and serum alpha-fetoprotein (AFP). Oncofetal markers CA 125 and CA 19-9 are
      elevated in serum of patients with various gastrointestinal diseases and
      malignancy. To study the biology of oncofetal antigens in tyrosinemia and to
      assess the possible usefulness of these markers in HTT-I, we studied serum
      concentrations of CA 125 (n = 160) and CA 19-9 (n = 188), together with AFP (n =
      337), in serial samples from 10 patients. At early stages of the disease, most
      children with an acute type of disease had a remarkably elevated serum CA 125
      concentration (153-1560 IU/L) that normalized gradually after the institution of
      therapy. Serum CA 125 levels may thus reflect acute metabolic imbalance in
      fulminant HTT-I. The patients with a chronic type of disease showed CA 125 levels
      within the normal range at diagnosis that slowly increased as the liver condition
      worsened. These concentrations, however, never reached values seen in acute HTT
      I. Serum concentration CA 19-9 in HTT-I was mostly normal. Serum AFP levels
      fluctuated in all patients and positively correlated with tests for metabolic
      state and biliary function. A distinct increase in the serum AFP level was
      recorded in association with the detection of massive hepatocellular carcinoma
      and also preceded metabolic imbalance leading to porphyria crises.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7513080
TI  - Screening infants and young children for developmental disabilities. American
      Academy of Pediatrics Committee on Children with Disabilities.

PMID- 7513081
TI  - A nuclear factor that binds purine-rich, single-stranded oligonucleotides derived
      from S1-sensitive elements upstream of the CFTR gene and the MUC1 gene.
AB  - We have identified two regions of non-random purine/pyrimidine strand asymmetry
      that were nearly identical in sequence in the 5' flanking (promoter) regions of
      the human cystic fibrosis transmembrane conductance regulator (CFTR) gene and the
      human MUC1 gene. These regions contain perfect mirror repeat elements, a sequence
      motif previously found to be associated with the formation of H-DNA
      conformations. In this report we demonstrate that a single-stranded non-B DNA
      conformation exists at low pH in supercoiled plasmids containing the similar
      mirror repeat elements, and that S1 nuclease digestion maps the single-stranded
      region to the position of the mirror repeats. In addition, we identify a nuclear
      protein of approximately 27 kD that binds to single-stranded oligonucleotides
      corresponding to the purine-rich strand of this region, but not to the pyrimidine
      rich strands or to double-stranded oligonucleotides with corresponding
      purine/pyrimidine strand asymmetry.

PMID- 7513084
TI  - Sequence of a cDNA from Linum usitatissimum encoding the stearoyl-acyl carrier
      protein desaturase.

PMID- 7513082
TI  - 1,N6-etheno deoxy and ribo adenosine and 3,N4-etheno deoxy and ribo cytidine
      phosphoramidites. Strongly fluorescent structures for selective introduction in
      defined sequence DNA and RNA molecules.
AB  - Synthesis of 1,N6-etheno-2'-deoxyadenosine, 3,N4-etheno-2'-deoxycytidine, and
      further chemistry on both deoxy and ribo series etheno nucleosides produces the
      corresponding phosphoramidites. These novel phosphoramidites are introduced
      selectively, quantitatively, and at specific positions at single or multiple
      sites into DNA or RNA sequences. The purification and chemistry involved in the
      synthesis of these products has been optimized to achieve the purity in excess of
      99%. The resulting phosphoramidites were tested for their ability to couple and
      produce poly deoxy and ribonucleotides by solid phase chemistry. The coupling
      efficiency achieved was greater than 99% per step. Due to the instability of
      these etheno compounds in acidic and basic medium, various criteria to obtain
      pure oligomers have been established. The selective introduction of these
      fluorescent nucleosides into defined sequence DNA and RNA molecule will greatly
      facilitate the structure-function studies of various RNAs, protein-RNA
      structures, and DNA-RNA based diagnostics applications. The characteristic and
      high fluorescent intensity (detection below 1 x 10(-9) M for adenosine sites and
      below 1 x 10(-7) M for cytidine sites) is particularly suited for the biochemical
      and biological research and product development applications. The usefulness of
      these etheno containing modified sequences as sequencing and amplification
      primers is demonstrated by their full participation in polymerase chain reaction
      experiments.

PMID- 7513083
TI  - Genes encoding glycine-rich Arabidopsis thaliana proteins with RNA-binding motifs
      are influenced by cold treatment and an endogenous circadian rhythm.
AB  - We have characterized the expression of two members of a class of Arabidopsis
      thaliana glycine-rich, putative RNA-binding proteins that we denote Ccr1 and
      Ccr2. Southern blot analysis indicates that Ccr1 and Ccr2 are members of a small
      gene family. Both Ccr1 and Ccr2 mRNA levels were influenced by a circadian rhythm
      that has an unusual phase for plants, with maximal accumulation at 6:00 PM and
      minimal accumulation at 10:00 AM. The level of CCR1 protein, however, remained
      relatively constant throughout the cycle. The transcript accumulation patterns of
      the Ccr1 and Ccr2 genes differed considerably from conditions that affect the
      expression of similar genes from maize, sorghum, and carrot. Levels of Ccr1 and
      Ccr2 mRNAs were unchanged in wounded plants, increased at least 4-fold in cold
      stressed plants, and decreased 2- to 3-fold in abscisic acid-treated plants. Ccr1
      transcript levels decreased in response to drought, whereas Ccr2 transcript
      levels increased under the same conditions. Based on the presence of additional
      Ccr transcripts in dark-grown plants, we propose that Ccr transcripts may be
      subjected to a light- or dark-mediated regulation.

PMID- 7513085
TI  - [Establishing contact in the early stage of severe craniocerebral trauma: sound
      as the bridge to mute patients].
AB  - Both from a theoretical perspective and by means of several case examples, the
      article focuses on the issue of overcoming the disturbed pre-verbal communication
      behaviour presented by patients in the early stage following severe
      craniocerebral trauma. In patients with brain lesion, a pre-verbal, emotionally
      focussed tonal language almost invariably is capable of reaching the still
      healthy sections of the person. Hence, it is possible for music therapy to both
      establish contact with the seemingly non-responsive patient and re-stimulate the
      person's fundamental communication competencies and experience at the emotional,
      social and cognitive levels.

PMID- 7513086
TI  - Genitourinary problems in the elderly patient.
AB  - Dramatic advances across several fronts have provided a marked improvement in the
      quality of life for the elderly urologic patient. Radical surgery for cancer is
      much safer than in the past, and our focus is on preservation of function or
      complete functional reconstruction. In other areas we strive to continue to
      deliver excellent treatment while minimizing patient morbidity. This is seen most
      dramatically in the treatment of urinary stone disease. Ongoing work in patients
      with BPH promises to provide similar benefits to this population in the coming
      years. At the same time, we must remember that our abundance of therapeutic
      options imposes a responsibility to individualize treatment so as to best serve
      each patient.

PMID- 7513087
TI  - Laparoscopic ileal-loop conduit.
AB  - We describe our experience with a laparoscopic ileal-loop conduit technique for
      an elderly high-risk patient with bladder cancer. Four ports were used. The ileal
      segment was sectioned and isolated, ileal continuity was restored, and the ureter
      was implanted into the ileal segment conduit, extracorporeally. Conduit stoma was
      formed in one port. Operating time: 4 h. Recovery uneventful. The patient was
      discharged on the sixth postoperative day and is symptom-free at present and
      under radiotherapy.

PMID- 7513088
TI  - Repeated hepatic resection for recurrent hepatocellular carcinoma in eighteen
      cases.
AB  - BACKGROUND: Although intrahepatic recurrence after hepatic resection for
      hepatocellular carcinoma is the most significant cause of death, very few reports
      are available for hepatic re-resection as a radical treatment for recurrence.
      METHODS: Eighteen patients who underwent repeated hepatic resections for
      hepatocellular carcinoma were evaluated. Most of the patients regularly received
      measurement of alpha-fetoprotein level once a month and examination by
      ultrasonography and/or computed tomography scanning once every 3 to 4 months.
      RESULTS: No operative deaths occurred. The alpha-fetoprotein levels of 9 of the
      18 patients were within the normal range. Most patients underwent limited hepatic
      resection to maintain the remaining hepatic function. The 1-, 3-, and 5-year
      cumulative survival rates after repeated resection were 88%, 37%, and 37%,
      respectively. The 3-, 5-, and 7-year survival rates after the first resection
      were 88%, 68%, and 45%, respectively. These showed no significant difference from
      the survival rates of patients with no recurrences after hepatic resection.
      CONCLUSIONS: Careful follow-up examinations after hepatic resection are needed
      for early detection of recurrences, and efforts should be made for repeated
      hepatic resection, which leads to satisfactory outcome.

PMID- 7513089
TI  - Tenascin function and regulation of expression.
AB  - Tenascin is a large hexameric extracellular matrix protein. Each subunit consists
      of a linear array of the following structural domains: an N-terminal cysteine
      rich region and heptad repeats both involved in the oligomerization, followed by
      EGF-like repeats, fibronectin type III domains and a C-terminal globular domain
      homologous to fibrinogens. Depending on the species, the number of EGF-like
      repeats as well as of the fibronectin type III repeats differs. A model proposing
      a new nomenclature for the numbering of the fibronectin type III repeats is
      presented. It enables the assignment of corresponding repeats from different
      species and shows that for human tenascin several more alternatively spliced
      fibronectin type III repeats have been described than for chicken or mouse
      tenascin. Tenascin is generally classified as an anti-adhesive protein, since
      many cells do not adhere to tenascin or if they adhere they do not spread. The
      addition of tenascin can also lead to the loss of focal contacts in well spread
      cells. On the other hand growth cones adhere well to tenascin and a tenascin
      substrate can support neurite extension. Using recombinant fragments of tenascin
      we could identify an adhesive as well as an anti-adhesive region within one
      tenascin subunit. The major interest in tenascin was prompted by its interesting
      tissue distribution. Tenascin is often transiently expressed during
      organogenesis, tissue remodeling, cell migration and the development of the
      nervous system. We thus investigated possibilities to regulate tenascin
      expression in primary chick embryo fibroblast cultures.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7513090
TI  - Involvement of cell motility in tumor progression.
AB  - Since one crucial step in tumor progression consists of the acquisition of
      invasive and metastatic properties, it is important to analyze the mechanisms
      used by cancer cells to disperse. Among the possible mechanisms of cell
      dispersion, cell motility appears as a central phenomenon that still needs to be
      understood at the molecular level. Our experimental approach to the contribution
      of cell motility in carcinoma cell dissemination is based on the study of the NBT
      II rat bladder carcinoma cell line. The epithelial cell line gives rise to
      isolated, actively migrating, fibroblast-like cells in response to specific
      stimuli (collagens and acidic fibroblast growth factor [aFGF]). Analysis of the
      scattering response indicates that the different stimuli can synergize, leading
      to increased motility and invasiveness. NBT-II cells have two types of response
      to aFGF: they can either proliferate or scatter. In addition, the two responses
      are mutually exclusive, suggesting that the cell status can dictate whether or
      not tumor cells will disperse after exposure to a scatter factor. Finally, recent
      studies on the involvement of epithelial-specific cadherins in the process of
      aFGF-induced cell scattering indicate that a sustained expression of E-cadherin
      is not sufficient to protect cells from dispersing. In conclusion, our
      experimental model offers the opportunity to dissect the molecular events leading
      to tumor cell dissemination.

PMID- 7513092
TI  - Antiplatelet effects of ticlopidine are reduced in experimental
      hypercholesterolemia.
AB  - This study determines the antiplatelet effects of oral ticlopidine (100 mg/kg x
      day) in experimental hypercholesterolemia. Rabbits were fed either a standard
      diet or a cholesterol-enriched diet (0.5% for 3 months, 1% for 1 month). In
      normocholesterolemic controls ADP-, but not collagen-induced platelet aggregation
      was inhibited by ticlopidine treatment. This was accompanied by a significantly
      enhanced inhibition of ADP-induced platelet aggregation and stimulation of cyclic
      AMP accumulation by iloprost. Hypercholesterolemia considerably attenuated the
      inhibition of ADP-induced aggregation by ticlopidine but did not change its
      effect on the iloprost-induced inhibition of platelet function and cyclic AMP
      formation. ADP-induced platelet-derived thromboxane formation was considerably
      greater in hypercholesterolemic rabbits and not reduced by ticlopidine.
      Ticlopidine did also not significantly influence the extent and severity of
      atherosclerotic plaque formation although a tendency for improvement was observed
      in a subgroup of animals. The data suggest that hypercholesterolemia attenuates
      the inhibitory effect of ticlopidine on ADP-induced platelet aggregation. This
      might be related to the stimulation of thromboxane formation by ADP in
      hypercholesterolemia. The maintained protection from ADP-induced inhibition of
      cAMP accumulation suggests a minor role of this mechanism in the progression of
      hypercholesterolemia-induced vessel disease in this model.

PMID- 7513091
TI  - Comparison of functional assays for protein S: European collaborative study of
      patients with congenital and acquired deficiency.
AB  - Four functional assays for protein S were evaluated by 4 different laboratories,
      each center using its own method. The aim of this study was to compare these
      different assays and to establish a relationship with results of immunological
      assays of total and free protein S antigen and C4bBP. The same plasma samples
      were distributed to each center and tested in blind. In 47 normal subjects, there
      was no significant difference between the 4 functional assays, with mean values
      ranging from 93 to 100%. These values were in good agreement with those of free
      and total protein S antigen. In 34 patients with a quantitative congenital
      deficiency of protein S the mean values of protein S activity were decreased with
      the 4 assays, ranging from 25 to 40%. Free protein S antigen was reduced to a
      similar extent, whereas total antigen was either normal or decreased. The
      correlation of protein S activity with free protein S antigen was satisfactory
      for 3 methods, with coefficients of correlation varying from 0.84 to 0.92 whereas
      it was only 0.70 in one lab. When total protein S antigen was reduced, protein S
      activity was decreased in all the patients with the 4 assays. In contrast when
      total protein S antigen was normal an important overlap of protein S activity
      between normals and patients was observed in one lab with 12 patients
      misclassified. In 8 patients with a functional defect, results of protein S
      activity differed substantially according to the assay used and about half of
      these patients were misclassified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513095
TI  - Effect of nitric oxide syntase inhibition on cerebral blood flow and injury
      volume.

PMID- 7513094
TI  - Characterization of a monoclonal antibody directed against the carboxyl-terminus
      of human factor XIII. An epitope exposed upon denaturation and conserved across
      species lines.
AB  - By deriving an anti-peptide monoclonal antibody, mAb 7A4, we characterized the
      relatively unstudied carboxyl-terminal end of the a-chain of human factor XIII,
      the plasma transglutaminase. MAb 7A4 was directed against the last eight amino
      acids (Gln-Ile-Gln-Arg-Arg-Pro-Ser-Met) and bound with a dissociation constant of
      3.4 x 10(-8)M. In a solid assay format, mAb 7A4 bound equally well to factor XIII
      obtained from human plasma, platelets or placenta. However, in a solution-phase
      assay format, the epitope was largely unavailable but could be readily exposed by
      heat denaturation. Immunoblotting showed that this epitope is conserved among all
      species of plasma factor XIII tested except rabbit suggesting that the carboxyl
      terminus might be an important structural element. Other competitive binding
      experiments with synthetic peptides as inhibitors pointed toward the final
      carboxyl-terminal amino acid, Met-731, as an immunochemically important
      determinant. This was used advantageously to confirm the finding that the
      carboxyl-terminal Met-731 is largely absent from placental factor XIII (1) as
      compared to platelet or plasma factor XIII.

PMID- 7513093
TI  - Increased urokinase-type plasminogen activator (u-PA) levels in graft liver
      perfusate and decreased single chain u-PA activation with higher levels of
      aprotinin.
AB  - In orthotopic liver transplantation (OLT) the graft liver is perfused with
      arterial blood prior to the opening of the hepatocaval anastomosis. In the
      present investigation we focused on the reperfusion of the graft liver in order
      to study the hepatic influence in the regulation of urokinase-type plasminogen
      activator (u-PA levels). Two different aprotinin schedules were used in 43
      patients. We measured u-PA levels in the perfusate and in the corresponding
      systemic circulation. u-PA levels were higher in the perfusate as compared to
      systemic blood samples despite the dilution of the perfusate sample by the
      preservation fluid. This suggests u-PA secretion by the graft liver. In the
      presence of lower aprotinin levels signs of single-chain u-PA (scu-PA) activation
      was in the perfusate more prominent than systemically--a difference which was not
      seen in the presence of higher aprotinin levels. This seems to be an argument for
      the effectiveness of higher dosed aprotinin application in preventing scu-PA
      activation.

PMID- 7513096
TI  - Differences in rejection grading after simultaneous pancreas and kidney
      transplantation in pigs.
AB  - Clinical observations suggest that recipients of multiorgan transplants from the
      same donor can have disparate immunological reactions to each organ. We studied
      this phenomenon in 36 diabetic (streptozotocin-induced), bilaterally
      nephrectomized, immunosuppressed (cyclosporine, azathioprine, prednisone) pig
      recipients of simultaneous (same donor) pancreas (bladder drained) and kidney
      allografts by grading the histological intensity of rejection in biopsies of each
      organ at defined intervals posttransplant. Graft function was monitored by plasma
      glucose (PG) and urine amylase (UA) for the pancreas and serum creatinine (Cr)
      for the kidney. Interstitial rejection was graded as absent, mild, moderate, and
      severe in, respectively, 8%, 25%, 42%, and 25% of pancreas vs. 4%, 12%, 27%, and
      57% of kidney biopsies at 1 week; and 0%, 43%, 29%, and 29% of pancreases vs.
      10%, 0%, 30%, and 60% of kidneys at two weeks. Although the distribution of
      grades was similar in the two organs (P > 0.1), the grade of rejection for each
      pair at 1 week (n = 24) was discordant in 75% (42% differed by one and 33% by >
      or = 2 grades) and at 2 weeks (n = 7) in 57% (29% by 1 and 29% by > or = 2
      grades). The inability to use the severity of interstitial rejection in one organ
      to predict the findings in the other is exemplified by the fact that for the two
      pancreases without interstitial rejection at one week, the corresponding kidney
      showed moderate or severe rejection, and for the 1 kidney without rejection the
      corresponding pancreas showed moderate rejection. Vascular rejection grades
      (absent, mild, moderate, severe) also showed a similar distribution for the
      pancreas (57%, 30%, 9%, 4%) vs. kidney (50%, 38%, 0%, 12%) at 1 week, and at 2
      weeks (57%, 29%, 0%, and 14% for the pancreas vs. 78%, 11%, 0%, and 11 for the
      kidney) (P > or = 0.64). However, the grading of vascular rejection in organ
      pairs was dyssynchronous in 54% at 1 week (n = 22) and 29% at 2 weeks (n = 7). No
      vascular rejection in the pancreas with rejection in the kidney was seen in 5
      pairs at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kidney
      with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at
      2 weeks (29%).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7513097
TI  - Human natural antibodies to porcine platelets.
AB  - The specificity of human natural antibodies directed against blood cells from
      pigs was investigated by ELISA and immunoblotting. Both IgG and IgM were
      identified as xenoantibodies reacting with pig platelets adsorbed to microplates.
      The antibodies could be absorbed on platelets as well as on RBC, suggesting that
      the corresponding antigens are expressed on the surface of a variety of cells.
      Galactose (20 mM) and melibiose (10 mM) partially inhibited (approximately 50%)
      the binding of antibodies to platelets, whereas lactose and cellobiose (300 mM)
      did not. On immunoblots, platelet glycoproteins of 115, 125, 135, 180, and 210
      kDa were specifically revealed with human sera diluted 1/20. In contrast with the
      results obtained by ELISA, xenoantibodies reactive with blotted glycoproteins
      were of the IgM class and the binding was not significantly inhibited by
      galactose or melibiose. "Anti-Gal" antibodies, purified from human sera by
      affinity chromatography on a melibiose-Sepharose immunoabsorbent, represented
      only a minor portion of the antibodies reactive with porcine platelets. Purified
      anti-Gal antibodies bound to the 115- and 135-kDa components, whereas the
      antibodies in the nonretained fraction revealed the 125-kDa molecule. As deduced
      from these data, human serum contains natural antibodies of both IgG and IgM
      classes directed to several porcine antigens. Gal-reactive structures were
      identified on the 115- and 135-kDa platelet glycoproteins, which might be
      homologous to their counterpart on endothelial cells. Also, the present work
      suggests that a majority of the natural antibodies reacted with other
      unidentified structures.

PMID- 7513098
TI  - Reversal of gastrointestinal toxicity associated with long-term FK506
      immunosuppression by conversion to cyclosporine in liver transplant recipients.

PMID- 7513100
TI  - Angiosuppressive therapy for cancer.

PMID- 7513099
TI  - Acute renal failure associated with the use of ibuprofen in two liver transplant
      recipients on FK506.

PMID- 7513101
TI  - Diagnosis of Trichomonas vaginalis in male urethritis.
AB  - Trichomonas vaginalis was diagnosed in 42 (19%) of 227 adult males with urethral
      discharge. In 27 men (15%) T. vaginalis was isolated together with Neisseria
      gonorrhoeae. Non-gonococcal urethritis was diagnosed in 15 patients and T.
      vaginalis was isolated from 47% of such patients. Stained smear preparations,
      i.e. RapiDiff and acridine orange of modified Diamond's media, were superior to
      wet smear microscopy for the identification of T. vaginalis. RapiDiff stain was
      the most sensitive and identified 41 of 42 (98%) positive cultures. It is
      recommended that all turbid culture media should be stained for the optimal
      diagnosis of trichomoniasis.

PMID- 7513102
TI  - [The 3-dimensional organization of the nucleolus and nucleolus-organizer regions
      of differentiated cells. IV. The structural and functional heterogeneity of the
      nucleoli in the epithelium of the proximal nephron in the mouse].
AB  - By means of stereological and morphometrical analysis, the ultrastructure of
      nucleoli in epitheliocytes of mouse kidney cortex proximal tubuli has been
      studied. In accordance to the nucleolar composition, three main groups of
      nephrocytes with different levels of rRNA and protein synthesis were defined.
      Functional heterogeneity of proximal tubuli epithelium was established by
      correlation between different variants of ultrastructural organization of
      nucleoli and the total RNA synthesis activity, determined by 3H-uridine
      incorporation intensity. It has been shown that a greater part of cells (about
      52%) in the nephron proximal section, which is characterized by slow RNA
      synthesis, causing a low functional activity of these cells, presumably
      represents a reparative cellular reserve. Such cells, defined as the 1st group
      cells, have resting, ring-shaped nucleoli with one fibrillar centre, and nucleoli
      similar to the ring-shaped ones but containing 2-3 fibrillar centres. Nucleoli of
      the 2nd group of nephrocytes (about 37%), most actively incorporating labeled
      precursor, contain 4-6 fibrillar centres. Their structural organization is closer
      to the reticular type of nucleoli. The 3rd most actively labeled group of
      nephrocytes includes cells with typical reticulated nucleoli. The number of
      fibrillar centres in the reticulated nucleoli is much higher (18-22) than in the
      1st and 2nd groups of nephrocytes. Structural and functional polymorphism of
      nephrocytes was revealed not only in the proximal part of one nephron. During the
      increase in functional activity of nephrocytes, caused by unilateral nephrectomy,
      the quantitative correlation between cells related to these different groups was
      seen to change. The number of cells of the 1st group decreased by 24%, whereas
      that in the 2nd and 3rd groups increased by 9 and 15%, respectively. Nucleoli
      with 2-3 fibrillar centres are considered as transitional forms between the
      inactive ring-shaped nucleoli and the active reticulated nucleoli. Differences in
      the ultrastructure of nucleoli may be considered as an evidence of functional
      heterogeneity of nephrocytes within the proximal segment of nephron.

PMID- 7513103
TI  - Child health, the genome project and phenylketonuria.
AB  - Child health and life expectancy improved together in many societies in the 20th
      century. As the incidence of diseases with major extrinsic causes declined, the
      heritability of disease as a whole increased. Accordingly, the genetic
      (intrinsic) causes of disease have become important. The genome project is an
      international venture out of which will come new knowledge about the biological
      basis of health and disease, and technologies to apply that knowledge in medicine
      and other disciplines. Phenylketonuria (PKU) at one time was seen only as a rare
      inborn error of metabolism causing severe mental retardation. Yet, the gene
      frequency is about 1% in Caucasian and Oriental populations, higher still in some
      populations with particular histories that have enhanced gene frequency. These
      genetic facts make PKU a paradigm in human genetics. This genetic disease, for
      which it was thought there was nothing to be done, has yielded to inquiries at
      clinical, metabolic, protein (enzyme) and DNA (PAH gene) levels. Results have
      shown that, early diagnosis (by population screening) and treatment (by low
      phenylalanine diet) largely prevents mental retardation. DNA analysis reveals
      particular associations between PKU mutations, RFLP haplotypes and populations;
      these associations are relevant for counseling. PKU illustrates well how medical
      science, molecular biology and gene mapping can improve knowledge and contribute
      to child health.

PMID- 7513104
TI  - Serum PSA adjusted for volume of transition zone (PSAT) is more accurate than PSA
      adjusted for total gland volume (PSAD) in detecting adenocarcinoma of the
      prostate.
AB  - OBJECTIVE: This study evaluates the accuracy of comparing serum prostate-specific
      (PSA) levels in the range between 4.1 ng/mL and 10.0 ng/mL (monoclonal) to the
      volume of the transition zone (TZ) of the prostate and total gland volume as a
      predictor of a positive biopsy. METHODS: Using sonographic voluming of the entire
      prostate and of the TZ, prostate-specific antigen density (PSAD) and prostate
      specific antigen density of the TZ (PSAT) were calculated in 21 biopsy-positive
      patients and 38 biopsy-negative patients. Biopsy was directed at sonographically
      suspicious areas and did not include sextant biopsies. RESULTS: A statistically
      significant association was determined between a positive biopsy and gland
      volume, TZ volume, and PSAT. The association of a positive biopsy with PSA and
      PSAD was not statistically significant. CONCLUSIONS: PSAT is more accurate in
      predicting a positive biopsy than is PSAD for PSA levels between 4.1 ng/mL and
      10.0 ng/mL.

PMID- 7513105
TI  - Risk factors for bacteriuria in men.
AB  - OBJECTIVE: To identify risk factors for bacteriuria in a selected group of
      institutionalized men. METHODS: A total of 99 men, mean age seventy-one years,
      range forty-eight to one hundred four years, living in a nursing home were
      evaluated for diagnoses of benign prostatic hyperplasia (BPH) and diabetes
      mellitus (DM), symptoms of bladder outlet obstruction, and postvoid residual
      urine volume (PVR). At the time of evaluation urine cultures were performed for
      all subjects. Urinalyses had been performed in all men within the two years prior
      to initiation of the study. Residents unable to give informed consent, with a
      history of cancer of the prostate or bladder, previous urethral or prostate
      surgery, or inability to void in the standing position were excluded. RESULTS:
      Prior to or during the study 30 residents had bacteriuria, which was not
      correlated with age, PVR, previous diagnoses of BPH or DM, or with obstructive or
      irritative urinary symptoms consistent with bladder outlet obstruction.
      CONCLUSIONS: Competent, institutionalized residents with higher functional levels
      meeting the inclusion criteria were not at a high risk of bacteriuria. The
      concept that increased PVR per se predisposes to bacteriuria cannot be
      substantiated.

PMID- 7513106
TI  - Natural history of prostatism: worry and embarrassment from urinary symptoms and
      health care-seeking behavior.
AB  - OBJECTIVE: To assess the interrelationships among psychosocial symptoms of worry
      and embarrassment about urinary function, prevalent urinary symptoms,
      psychological well-being, and health care-seeking behavior in a population-based
      cohort of men. METHODS: A cohort of 2,119 men aged forty to seventy-nine years,
      randomly selected from the Olmsted County, Minnesota population between December
      1989 and March 1991, were administered a previously validated questionnaire that
      elicited information about the frequency of urinary symptoms, the degree to which
      they were perceived as a bother, and if the participant had seen a doctor in the
      previous twelve months for evaluation of any of these urinary symptoms.
      Psychological well-being was assessed by a subset of the Psychological General
      Well-Being Index, and sociodemographic information was also sought. RESULTS:
      Urinary symptom indices (measured by American Urological Association frequency
      and bother scores and psychological general well-being subscales) were
      significantly associated with worry and embarrassment about urinary symptoms in
      bivariate analyses. Multiple logistic regression analyses demonstrated that men
      with moderate or severe urinary symptoms or impaired psychological well-being
      were more likely to be worried or embarrassed about their urinary symptoms than
      men with mild symptoms. Furthermore, men who were worried about their urinary
      function were more likely to have sought medical care for their symptoms than men
      who were not worried. The association between health care-seeking behavior and
      embarrassment was especially strong among men with little bother associated with
      their urinary symptoms. CONCLUSIONS: Worry and embarrassment about urinary
      symptoms reflect quality-of-life issues that appear important in the health care
      seeking behavior of men with prostatism. The results underscore findings that
      prevalent urinary symptoms alone do not determine a man's health care-seeking
      behavior, and treatment for psychosocial symptoms may be beneficial in some men
      with symptoms of prostatism.

PMID- 7513107
TI  - Predictive value of prostate-specific antigen density for the presence of
      micrometastatic carcinoma of the prostate.
AB  - OBJECTIVE: To examine the efficacy of prostate-specific antigen (PSA) density
      (PSAD; serum PSA/prostate volume) as a predictor of clinical outcome of patients
      undergoing radical retropubic prostatectomy for clinically confined prostate
      cancer, and its ability to determine the presence of micrometastatic disease.
      METHODS: A retrospective analysis of patient outcome as reflected by surgical
      stage and postoperative PSA was performed with respect to PSAD as determined by
      preoperative PSA and pathologic prostate gland volume. The findings for 107
      consecutive patients who underwent radical prostatectomy are reported. RESULTS:
      PSAD at low values was found to be 90 percent accurate in predicting operative
      success or absence of micrometastatic disease. PSAD at high values was shown to
      be 70 percent accurate in predicting failure. CONCLUSIONS: PSAD appears to be
      useful in selecting patients for radical prostatectomy and may be capable of
      identifying patients with micrometastatic disease.

PMID- 7513109
TI  - Qualitative and quantitative evaluation of prostatic histomorphology in rats
      following chronic treatment with finasteride, a 5-alpha reductase inhibitor.
AB  - OBJECTIVE: To determine any potential direct and/or indirect effects of elevated
      intraprostatic T levels on the prostates of rats chronically (1-2 years) exposed
      to high doses (160 mg/kg/day) of finasteride, a selective inhibitor of 5-alpha
      reductase. METHODS: Sprague-Dawley male rats were administered daily finasteride
      by oral gavage. Prostates from all rats were weighed, fixed in 10% neutral
      buffered formalin, and processed for light microscopic examination. The volume
      fractions of the prostatic glandular and stromal compartments were quantitated by
      morphometric analysis. RESULTS: Administration of finasteride at doses of 20, 40,
      and 80 mg/kg/day for one year resulted in a significant (P < or = 0.05) decrease
      in prostatic weight; prostatic atrophy was evident by light microscopy.
      Morphometric analysis of the prostate showed that chronic finasteride
      administration resulted in a significant (P < or = 0.001) decrease in the
      absolute volume of both glandular (-65.2%) and stromal (-57.1%) compartments of
      the prostate. Furthermore, the total number of epithelial and stromal cells per
      gland were significantly (P < or = 0.002) decreased in finasteride-treated rats
      compared with vehicle controls; the magnitude of mean decrease was 69.8 percent
      and 50.6 percent of controls in epithelial and stromal cells, respectively. In
      addition, prostates from all two hundred fifty rats in a two-year study were
      qualitatively evaluated by light microscopy. Administration of finasteride at
      doses ranging from 2.5 mg/kg/day to 160 mg/kg/day for two years did not result in
      an increase over the background incidence of prostatic focal hyperplasia or
      adenoma. No malignant tumors of the prostate were seen in any of the groups.
      CONCLUSIONS: These studies have demonstrated that the expected pharmacologic
      effects of finasteride on the prostate are maintained following chronic treatment
      and that there was no evidence of a direct and/or an indirect effect of elevated
      intraprostatic T on prostatic morphology in rats.

PMID- 7513108
TI  - Evaluation of serum prostate-specific antigen velocity after radical
      prostatectomy to distinguish local recurrence from distant metastases.
AB  - OBJECTIVE: Serum prostate-specific antigen (PSA) values are most useful for
      prediction of disease recurrence after surgery. It is unknown whether a
      detectable PSA level after surgery indicates a local recurrence potentially
      benefiting from pelvic irradiation or distant metastases requiring hormonal
      treatment. METHODS: We analyzed postoperative rate of change of serum PSA levels
      as a predictor of local versus distant disease recurrence after radical
      prostatectomy. Between 1982 and 1991, 1,058 men underwent radical prostatectomy
      for localized prostate cancer and follow-up consisted of determining serum PSA
      levels and digital rectal examinations. Clinical follow-up of 542 men for four or
      more years and 78 men for eight or more years yielded ten-year actuarial disease
      recurrence rates of 4 percent for local recurrence, 8 percent for distant
      metastases, and 23 percent for an isolated elevation of serum PSA level only.
      Fifty-one patients with isolated elevations of PSA levels only were followed
      expectantly until they were diagnosed with either local or distant metastases.
      RESULTS: A linear mixed effects regression analysis was used to model these data.
      Using these models, the time to a serum PSA level of 0.5 ng/mL, the PSA level one
      year following surgery, pathologic stage, Gleason sum, and the rate of change of
      PSA (PSA velocity [PSAV]) were tested as predictors of local versus distant
      metastases. A combination of PSAV, pathologic stage, and Gleason grade best
      distinguished local from distant metastases. CONCLUSIONS: These data suggest that
      PSAV in men with an isolated elevation of PSA levels following radical
      prostatectomy might aid in clinical decision making.

PMID- 7513110
TI  - Exophytic papillary prostatic duct adenocarcinoma with endometrioid features,
      occurring in prostatic urethra after TURP.
AB  - We present an eighty-three-year-old man with an exophytic lesion in the prostatic
      cavity, diagnosed three years after transurethral resection of the prostate, and
      extending into the bladder. Histopathologically, the tumor was recognized as a
      papillary ductal adenocarcinoma (primary duct type) with endometrioid features,
      probably associated with prostatic adenomatous polyp. Acinic adenocarcinoma was
      absent. The lesion was treated by deep transurethral resection with objective
      follow-up results after six months. Review of the literature concerning history,
      embryology, possible pathogenesis, differential diagnosis, and treatment options
      is included.

PMID- 7513111
TI  - Medical therapy for BPH.

PMID- 7513114
TI  - [Whipple's disease--a rare cause of secondary amyloidosis].
AB  - Two cases of Whipple's disease with secondary amyloidosis are described. One
      patient had a nephrotic syndrome, the other malabsorption. The chronic
      inflammatory stimulus of Whipple's disease is discussed as a trigger for the
      development of secondary amyloidosis. The clinical symptoms of seronegative
      arthritis, weight loss, chronic diarrhea, intermittent fever and lymphadenopathy
      may be the clue to the diagnosis of Whipple's disease. Peroral intestinal biopsy
      is the diagnostic procedure of choice. Adequate antibiotic treatment with a
      regimen of penicillin and trimethoprim-sulfamethoxazole is indicated and prevents
      the development of secondary amyloidosis.

PMID- 7513115
TI  - Immunological characteristics of a recombinant hepatitis B virus-derived multiple
      epitope polypeptide: a study in polyvalent vaccine design.
AB  - Immunological properties of a model polyepitope immunogen (MEP-1) consisting of
      selected determinants from envelope proteins of hepatitis B virus (HBV) were
      examined. Immunization with MEP-1 induced high-titre antibodies in a variety of
      murine strains and in rabbits although an overall hierarchy of B-cell
      immunodominance was observed as pre-S1-derived > S-derived > pre-S2-derived
      segments. Anti MEP-1 antibody responses in all hosts were found to be exclusive
      for HBV-derived sequences in the absence of any fraction directed against the
      various interepitope junctions. With panels of overlapping peptides it was
      observed that the anti-pre-S1 and anti-pre-S2 components of anti-MEP-1 antibodies
      were, in all animals tested, of the desired specificity from the standpoint of
      potential virus-neutralizing ability. The MEP-1 segment representing residues 124
      127 of the major protein of hepatitis B surface antigen (HBsAg) was found to
      elicit a conformation-specific antibody response. Furthermore, this subpopulation
      was either predominantly or exclusively against the Met133-Lys141-dependent group
      specific epitope. Finally, the HBV sequences in MEP-1 were shown to retain their
      Th-cell activities. These studies suggest that MEP-1 provides a useful tool in
      the study of polyvalent vaccine design.

PMID- 7513112
TI  - [The prevention and drug correction of cardiovascular changes in prostatic cancer
      patients].

PMID- 7513116
TI  - Electrophoretic migration of adenovirus hexon under non-denaturing conditions.
AB  - While SDS-PAGE/immunoblotting is a valuable approach for the characterization of
      monoclonal antibodies, the denaturing conditions involved can compromise the
      recognition of conformational epitopes. This report demonstrates that a group
      specific epitope on adenovirus hexon can be recognized by immunoblotting
      following SDS-PAGE provided that samples are not boiled prior to electrophoresis.
      Under these conditions, multiple bands corresponding to native forms of hexon
      were detected above the position of the denatured hexon monomer. Among
      representative serotypes of subgroups A, B and F, two predominant bands,
      corresponding to hexon trimers and 'group of nine' hexons (GONs), were routinely
      observed. In contrast, higher order structures, in addition to trimers and GONs,
      were characteristic of subgroup C adenoviruses. These serotypic differences in
      stability of hexon structures may reflect differences in protein-protein
      interactions within the corresponding virions.

PMID- 7513117
TI  - [After-care in colorectal cancer--data and patient oriented evaluation].
AB  - The results and the costs of a routine follow-up program for patients with
      curatively resected colo-rectal carcinoma were evaluated in a retrospective
      matched pair study. Patients, who never had participated in such a program, were
      used as controls. In addition 58 patients were questioned prospectively regarding
      their opinion about the value of the follow-up program for their present and
      future life. Significantly more local recurrences and distant metastases were
      diagnosed at an average of 1.5 years earlier in the follow-up group as compared
      with the control group. Neither the hereby resulting higher number of curatively
      resected local recurrences or distal metastases nor a more aggressive oncological
      approach in unresectable cases resulted in a substantial improvement of survival
      time in the follow-up group. Considering the relatively high costs of the
      program, only the diagnosis of several other illnesses which one was able to
      treat, and the high appreciation by the patients speak in favor of the follow-up
      program. 86.2% of the patients believed that routine follow-up would be of
      essential value for their future life.

PMID- 7513113
TI  - [Somatostatin receptor scintigraphy in neuroendocrine tumors exemplified by a
      patient with hepatic metastases of gastrinoma].
AB  - In a 66-year old woman, who suffered from recurrent melena, diarrhea and
      hematemesis with multiple untreatable gastric and duodenal ulcers, a markedly
      increased basal and secretin-stimulated gastrin level, clinically a Zollinger
      Ellison syndrome was assumed. The conventional diagnostic procedures (esophago
      gastro-duodenoscopy, colonoscopy, endosonography, ERCP, abdominal CT and small
      bowel enema) had failed to reveal the localisation of any gastrinoma. The
      thereupon performed scintigraphy with In-111-pentetreotide showed four
      somatostatin receptor expressing liver lesions: two of them could be detected at
      first site in the consecutively performed MR scans, another retrospectively
      bearing in mind the scintigraphic images. Today, the somatostatin receptor
      imaging seems to be a highly sensitive procedure for detecting and localizing
      hormonally active gastroenteropancreatic tumors. At the same time it is a method
      for in vivo evaluation of the somatostatin receptor status of localized GEP
      tumors, thus delivering a decisive diagnostic step for the evaluation of the
      effectiveness of a therapy with somatostatin analogues before such an expensive
      therapy is started.

PMID- 7513118
TI  - [A comparative analysis of monoclonal assays for the determination of PSA:
      radioimmunometric assay (ELSA) vs microparticle immunoenzyme assay (MEIA)].
AB  - Comparative analysis of PSA values measured by MEIA and ELSA techniques in a
      group of 70 unselected patients. A good correlation was observed between PSA
      levels determined by ELSA-PSA immunoradiometric techniques and those obtained by
      MEIA-PSA (r = 0.93, p < 0.00001). However, ELSA-PSA values have been 1.73 +/- 0.1
      times higher than those by MEIA-PSA. A mean-paired comparison indicates that PSA
      mean levels (0.48 +/- 0.07 and 0.29 +/- 0.05 for ELSA and MEIA, respectively) are
      significantly different and define two groups of nonhomogeneous values (p <
      0.0001). The same results are obtained when patients with PSA values higher and
      lower than 4 ng/ml are analyzed separately. For patients with PSA lower than 1
      ng/ml, the difference between mean ELSA-PSA and MEIA-PSA values disappears; 0.74
      +/- 0.08 vs 0.62 +/- 0.05, respectively (p > 0.1). In this group, the results
      from both assays are statistically consistent. When considering the group of
      patients with PSA < 1 ng/ml, no difference between both techniques becomes
      apparent, which seems to indicate the absence of differences in sensitivity
      between both techniques when considering low levels of serum PSA. Nevertheless,
      it is clear that the results from these techniques can not overlap and are not
      comparable and so, to all practical effects, it is recommended that follow-up of
      any particular patient is made always with the same technique and even at the
      same laboratory.

PMID- 7513119
TI  - [Immortalization of rat corneal epithelial cells by SV40-adenovirus recombinant
      vector].
AB  - Using a SV40-adenovirus recombinant vector, we have successfully established a
      rat corneal epithelial cell line (RatCE) and studied its biological
      characteristics. RatCE continued to grow for more than 400 generations. It
      proliferated centrifugally in the early phase of the culture (1-3 days in
      culture) and had a cobblestone-like appearance in confluency. Desmosomes and
      microvilli were clearly seen under a transmission electron microscope. RatCE
      could be stored in liquid nitrogen and its biological characteristics were:
      doubling time, 18.3 hrs, colony forming ability, 36%, and growth ability in soft
      agar, 2%. When the insoluble extract from RatCE was electrophoresed, insoluble
      proteins were seen at 36 kD, 40 kD, 44 kD, 48 kD, 56 kD, and 64 kD. Anti-64 kD
      cytokeratin antibody strongly reacted with numerous filaments in the cytoplasm of
      RatCE. Hence, RatCE possessed 64 kD corneal specific keratin. A large amount of
      fibronectin was also assessed at focal contact by immunohistochemistry. Thus,
      RatCE retains several kinds of epithelial characteristics, is derived from one
      clone, and is immortalized. RatCE will be a useful tool in studies of the corneal
      epithelium.

PMID- 7513120
TI  - Relation of the power spectrum of the QRS complex to the fractal geometry of the
      His-Purkinje system.

PMID- 7513121
TI  - Maternal serum alpha-fetoprotein screening for chromosomal abnormalities: a
      prospective study in women aged 35 and older.
AB  - OBJECTIVE: Our purpose was to determine the detection and false-positive rates
      for maternal serum alpha-fetoprotein measurement to screen for fetal Down
      syndrome and other chromosomal abnormalities in women > or = 35 years old. STUDY
      DESIGN: A total of 3896 women had serum maternal serum alpha-fetoprotein levels
      measured routinely before amniocentesis for the indication of advanced maternal
      age. RESULTS: Eighty-five percent (28/33) of fetal Down syndrome pregnancies had
      second-trimester risks of > or = 1:270 on the basis of a combination of maternal
      serum alpha-fetoprotein measurement and maternal age. Risks were also > or =
      1:270 in 63% of the unaffected pregnancies. Sex chromosome aneuploidies,
      translocations, and other nonautosomal chromosome abnormalities in this study
      population were not associated with altered maternal serum alpha-fetoprotein
      levels; 51.9% (14/27) of these, however, were also assigned risks of > or =
      1:270. CONCLUSIONS: Maternal serum alpha-fetoprotein screening is more accurate
      than age alone for assigning individual Down syndrome risk in pregnant women > or
      = 35 years old. Counseling for women in this age group should include information
      regarding the lower sensitivity of maternal serum alpha-fetoprotein screening for
      detecting fetal Down syndrome and other chromosomal abnormalities (especially sex
      chromosome aneuploidies) compared with offering amniocentesis to these women.

PMID- 7513122
TI  - Phosphorylation of vimentin is an intermediate step in protein kinase C-mediated
      glycoconjugate secretion.
AB  - We have previously shown that fibroblasts from patients with cystic fibrosis (CF)
      display a higher response to 4 beta-phorbol 12-myristate 13-acetate (PMA) than
      control fibroblasts for stimulation of both protein kinase C (PKC) cytosol-to
      membrane translocation and glycoconjugate secretion. In this study we took
      advantage of these cells with differential responsiveness to PMA to investigate
      the endogenous substrate(s) involved in PKC stimulation of glycoconjugate
      secretion after verification of cystic fibrosis transmembrane conductance
      regulator gene expression in control and CF fibroblasts. We show that a 57-kDa
      protein that was associated with cytoskeleton and was identified as vimentin by
      immunoblotting emerged as a good candidate for mediating PKC stimulation of
      glycoconjugate secretion. 1) Its phosphorylation by PMA was abolished by PKC
      inhibition or depletion. 2) In both control and CF fibroblasts, the PMA-induced
      increase in its phosphorylation preceded the phorbol ester stimulation of
      glycoconjugate secretion. 3) For both processes, the concentration-response
      curves were superimposable, with higher maximal levels for CF fibroblasts
      relative to controls. 4) PMA-stimulated 57-kDa protein phosphorylation, like PMA
      stimulated glycoconjugate secretion, was significantly increased by Ca2+. 5)
      Increased PMA phosphorylation of the 57-kDa protein as a result of okadaic acid
      inhibition of intracellular phosphatases was reflected in increased PMA
      stimulation of glycoconjugate secretion. In conclusion, 1) PMA phosphorylation of
      a cytoskeletal 57-kDa protein, identified as vimentin, appears to be an
      intermediate step in PKC stimulation of constitutive glycoconjugate secretion in
      human skin fibroblasts; and 2) this process is impaired in CF disease.

PMID- 7513124
TI  - Activation of PI 3-kinase in 3T3-L1 adipocytes by association with insulin
      receptor substrate-1.
AB  - Insulin treatment of adipocytes causes the rapid phosphorylation of the insulin
      receptor substrate-1 (IRS-1) on tyrosine. The phosphotyrosine [Tyr(P)] form of
      IRS-1 then complexes with the enzyme phosphatidylinositol (PI) 3-kinase. In this
      study, we have investigated the effect of this association on PI 3-kinase
      activity in 3T3-L1 adipocytes. Insulin stimulated cytosolic PI 3-kinase activity
      about sevenfold. This stimulation was maximal after 1 min of exposure of cells to
      insulin, persisted for at least 1 h, and occurred over the range of insulin
      concentrations that saturate its receptor. By means of immunoprecipitation of IRS
      1, it was shown that virtually all of the enhanced activity was due to PI 3
      kinase complexed with IRS-1. Moreover, the purified Tyr(P) form of IRS-1, either
      isolated from 3T3-L1 adipocytes or obtained by phosphorylation of the recombinant
      protein with the insulin receptor, markedly stimulated the activity of purified
      rat liver PI 3-kinase. These results show that the association of Tyr(P) IRS-1
      with PI 3-kinase activates the enzyme and thereby can explain the elevation of PI
      3,4-bisphosphate and PI 3,4,5-trisphosphate in vivo observed upon treatment of
      adipocytes with insulin.

PMID- 7513123
TI  - Differential acidic pH sensitivity of delta F508 CFTR Cl- channel activity in
      lipid bilayers.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is present in acidic
      intracellular vesicles. Human normal and delta F508 CFTR Cl- channel
      characteristics at pH 7.4 and pH 4.5 were determined by fusing Xenopus laevis
      oocyte plasma membranes containing the expressed channels to planar lipid
      bilayers. At pH 7.4, both channels exhibited linear current-voltage curves, a 10
      +/- 0.3-pS conductance using 800 mM CsCl, and a 9:1 Cl-/Cs+ discrimination ratio
      obtained from a 32 +/- 2 mV reversal potential with a fivefold gradient. At -80
      mV, the open probability (Po) of mutant CFTR was 53% that of normal CFTR.
      Reduction of the trans-pH from 7.4 to 4.5 had no effect on the above
      characteristics except for Po, where it caused a 47% reduction in normal CFTR Po
      (due to a 75% decrease in mean open time) and a 75% reduction in delta F508 CFTR
      Po (due to a 6-fold increase in mean closed time). Normal CFTR can thus function
      in the environment of acidic intracellular organelles, whereas activity of mutant
      CFTR would be greatly reduced. These results may be of significance to
      understanding the cystic fibrosis defect.

PMID- 7513125
TI  - Tyrphostins inhibit secretagogue-induced 1,4,5-IP3 production and amylase release
      in pancreatic acini.
AB  - We examined the role of protein tyrosine kinase inhibitors (tyrphostins) in
      secretagogue-induced inositol 1,4,5-trisphosphate (1,4,5-IP3) production and
      amylase secretion in rat pancreatic acinar cells. The data show that various
      specific cell-permeant tyrphostins (methyl 2,5-dihydroxycinnamate, tyrphostin 25,
      and genistein) inhibited the cholecystokinin octapeptide-, carbachol-, and
      bombesin-induced 1,4,5-IP3 production and amylase release. In digitonin
      permeabilized cells, tyrphostins decreased 1,4,5-IP3 accumulation and amylase
      release generated by directly stimulating G proteins with the weakly hydrolyzable
      GTP analogue guanosine 5'-O-(3-thiotriphosphate). Tyrphostins had no effect on
      vasoactive intestinal peptide-induced amylase secretion. In isolated pancreatic
      acinar membranes, cholecystokinin octapeptide caused a rapid increase in tyrosine
      phosphorylation of a synthetic peptide containing the 12-amino acid sequence
      around a tyrosine phosphorylation site in pp6osrc. These results provide evidence
      that tyrosine kinases are involved in the activation of phospholipase C by G
      protein-coupled receptors in pancreatic acinar cells.

PMID- 7513126
TI  - Neurohormonal regulation of histamine synthesis in isolated rabbit fundic mucosal
      cells.
AB  - In a population of rabbit fundic mucosal cells enriched in mucous and endocrine
      cells, gastrin and cholecystokinin octapeptide (CCK-8) were shown to increase
      dose-dependently histidine decarboxylase (HDC) activity with the same efficacy
      and high potencies [50% effective concentration (EC50) 0.389 +/- 0.041 and 0.275
      +/- 0.011 nM, respectively], whereas pentagastrin was less potent (EC50 2.90 +/-
      0.13 nM). L-365,260 and PD-135,666 inhibited gastrin- and CCK-8-stimulated HDC
      activity with a high potency [50% inhibitory concentration (IC50) 1.00 +/- 0.08
      and 4.2 +/- 0.7 nM for gastrin-stimulated and 1.95 +/- 0.21 and 1.78 +/- 0.12 nM
      for CCK-8-stimulated HDC activity, respectively], whereas L-364,718 was 50 to 100
      times less potent (EC50 100 +/- 2.5 and 91.2 +/- 3.1 nM, respectively on gastrin-
      and CCK-8-stimulated HDC activity). Carbachol also dose-dependently increased HDC
      activity (EC50 7.08 +/- 0.32 nM), and its effect was reversed by selective
      muscarinic-receptor antagonists with the following order of potency: pirenzepine
      (IC50 15.1 +/- 1.2 nM) > para-fluoro-hexahydro-siladifenidol (IC50 0.316 +/- 0.02
      microM) > 11-2[(2-[(diethyl-amino)-methyl]-1-piperidinyl)acetyl]-5,11-dihydro-6H-
      pyrido[2,3-b][1,4]benzodiazepine-6-one (IC50 28.5 +/- 1.1 microM). Moreover,
      gastrin and carbachol were able to modify slightly but significantly both the
      Michaelis constant (Km) and the maximal velocity (Vmax) of HDC in the same way
      (18-20% reduction of the Km and 25-30% increase of the Vmax).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7513127
TI  - Apical nonspecific cation conductances in rabbit cecum.
AB  - Rabbit cecum exhibits electrogenic Na absorption in vitro. However, because this
      transport process is not inhibited by amiloride nor does it demonstrate
      saturation kinetics typical of the amiloride-inhibitable Na channel, we
      considered whether the cecal transporter represented one of a recently described
      family of nonselective cation conductances or channels (NSCC). Both
      transepithelial and vesicle studies demonstrated that K, Cs, and Rb were
      transported via an apical conductance. Electrogenic transport was inhibited by
      divalent cations including Ca, Mg, and Ba but was unaffected by either lanthanum
      or gadolinium. Parallel studies in distal colon did not exhibit a similar
      response to either K substitution or Ba inhibition. Phenamil, verapamil, and
      nicardipine significantly inhibited the short-circuit current (Isc). stimulated
      by nominal Ca- and Mg-free conditions. Flux studies demonstrated a correlation
      between changes in Isc and Na transport. Microelectrode impalement studies
      suggested that there may be both NSCC and K conductance in the apical membrane.
      Planar bilayer studies identified a 190-pS cation channel that may correlate with
      the macroscopic transport properties of this epithelium. These studies are
      consistent with a model of cecal Na absorption mediated by a NSCC in the apical
      membrane; this may be the mechanism underlying the distinct epithelial transport
      characteristics of this intestinal segment.

PMID- 7513128
TI  - Dexamethasone inhibits mucosal adaptation after small bowel resection.
AB  - The present study examined the effects of dexamethasone on mucosal adaptation
      after massive small bowel resection. Rats underwent 80% jejunoileal resection or
      a sham operation and received either vehicle or 128 micrograms.kg-1.day-1 sc
      dexamethasone for 7 days. Dexamethasone infusion resulted in decreased weight,
      DNA content, and protein content in the duodenojejunal and ileal mucosa in both
      sham and resected rats. Sucrase, lactase, and maltase activities (all in mumol.g
      protein-1.min-1) in the duodenojejunal mucosa were elevated by dexamethasone
      infusion. By contrast, enzyme activities were elevated only in the ileal mucosa
      of dexamethasone-infused sham-operated rats compared with sham-operated control
      rats, and dexamethasone did not elevate enzyme activities in resected rats. We
      further examined whether the inhibitory effects of dexamethasone on mucosal
      adaptation may be related to changes in either insulin-like growth factor (IGF)
      or IGF binding protein (BP) serum levels. Serum IGF-I and IGF-II levels were
      markedly decreased in dexamethasone-infused resected and sham-operated rats. IGF
      BP-1 serum levels were elevated by dexamethasone treatment with a concomitant
      depression in serum IGF BP-2 levels. IGF BP-3 levels were lowered by
      dexamethasone treatment in sham-operated rats and by gut resection, and serum IGF
      BP-4 levels did not change. These results suggest that the growth-inhibiting
      effects of dexamethasone in small intestinal mucosa may be partially mediated by
      decreased serum IGF levels or by alterations in IGF activity associated with
      changes in serum levels of IGF BPs.

PMID- 7513129
TI  - Localization of amiloride-sensitive Na+ channels in intestinal epithelia.
AB  - Polyclonal antibodies raised against purified bovine renal papillary amiloride
      sensitive Na+ channels were used to localize Na(+)-channel proteins in mouse and
      piglet small intestine. Immunostaining using the avidin-biotin-peroxidase
      technique revealed epithelial Na(+)-channel epitopes localized to apical regions
      of villus enterocytes in jejunal tissues of both species. Anti-Na(+)-channel
      antibodies also stained apical borders of villus enterocytes in piglet ileum and
      apical borders of surface cells in the piglet distal colon. On immunoblots of
      jejunal, colonic, and renal tissues the anti-Na(+)-channel antibodies recognized
      one to three polypeptides of apparent molecular masses similar to those found in
      bovine renal epithelial Na(+)-channel protein (the 55-65, 110-116, and 150-kDa
      subunits). The antibodies also recognized a polypeptide in the 40- to 45-kDa
      range in mouse intestine, which is comparable to the 35- to 40-kDa subunit of a
      renal Na+ channel. The results demonstrate that epitopes comparable to those
      present in renal amiloride-sensitive Na+ channels are found in apical regions of
      absorptive epithelial cells in the mammalian small and large intestine.

PMID- 7513130
TI  - Superoxide dismutase potentiates platelet-activating factor-induced injury in
      perfused lung.
AB  - Platelet-activating factor (PAF) causes pulmonary hypertension and lung edema in
      animals and isolated perfused lungs by poorly understood mechanisms. Because
      oxidative mechanisms have been implicated in PAF-mediated cellular injury, we
      tested the hypothesis that superoxide anion (O2-.) contributes to PAF-induced
      lung injury by determining whether superoxide dismutase (SOD) could prevent the
      lung injury. Isolated rabbit lungs were perfused with PAF (100 nM) at a dose that
      caused transient hypertension and mild edema. Lungs pretreated with Cu,Zn SOD
      (100 U/ml) for 10 min developed persistent pulmonary hypertension and more lung
      edema formation in response to PAF. Enhanced responses to PAF also were observed
      in lungs perfused with 200 U/ml Cu,Zn SOD, but not with 10 or 40 U/ml Cu,Zn SOD.
      The higher doses of SOD also decreased thromboxane B2 levels in the perfusate.
      Potentiation of the PAF effect by Cu,Zn SOD was eliminated if the enzyme was
      inactivated or if the lung was treated with an anion channel blocker. The
      augmented PAF response in the presence of SOD was not altered by catalase (200
      U/ml) or by nitric oxide synthase inhibitor. The data suggest that excessive
      Cu,Zn SOD enzyme activity potentiates PAF-induced injury in perfused rabbit lung
      presumably by overscavenging extracellular O2.- generated from intercellular
      sources. The augmented responses to PAF are not directly attributable to
      increased hydrogen peroxide, nitric oxide-related products, or thromboxane A2
      production. These results suggest the new hypothesis that a balance between O2-.
      production and its metabolism determines vascular and endothelial responses to
      PAF.

PMID- 7513131
TI  - Increased acetylcholine release in tracheas from allergen-exposed IgE-immune
      mice.
AB  - Increased release of acetylcholine (ACh) from airway parasympathetic nerve
      endings is one mechanism that may contribute to increases in airway
      responsiveness in immunoglobulin E (IgE)-immune allergen-exposed animals. We
      measured ACh released from murine tracheas following electrical field stimulation
      in vitro. BALB/c mice were immunized by exposure to an aerosol of 1% ovalbumin in
      sterile phosphate-buffered saline for 20 min/day for 10 days. At this time,
      levels of ovalbumin-specific IgE were proportionately higher than ovalbumin
      specific IgG. As a control, nonimmune mice were similarly exposed to phosphate
      buffered saline alone. Forty-eight hours after the last aerosol, tracheas were
      removed for assessment of either the contractile responses to electrical field
      stimulation and a cholinergic agonist (methacholine or ACh) or release of ACh
      produced by electrical field stimulation. ACh in the bath was measured using high
      performance liquid chromatography with electrochemical detection. The stimulation
      frequencies causing one-half the maximal contractile response to electrical field
      stimulation were 4.1 +/- 0.2 and 2.8 +/- 0.2 Hz (P = 0.0001) for nonimmune and
      immune mice, respectively, whereas the molar concentrations of methacholine
      causing one-half of the maximal contractile response did not significantly
      differ. In addition, the dose-response curves of immune and nonimmune tracheas to
      ACh were superimposable. A significant increase in ACh release was demonstrated
      at both 10 and 20 Hz in tracheas from immune mice. ACh release (pmol.g tissue
      1.min-1) from nonimmune and immune murine tracheas, respectively, were 140 +/- 8
      and 205 +/- 22 (P = 0.013) at 10 Hz and 147 +/- 13 and 227 +/- 14 (P = 0.008) at
      20 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513132
TI  - Cameroon: an African model for final stages of guinea worm eradication.
AB  - The Cameroon Guinea worm eradication program initiated case containment
      activities in 1991 in the Mayo-Sava Division, the only endemic region in the
      country. These activities differed from the Pakistan program, the only other
      operational model for dracunculiasis case containment, in two important ways. In
      Cameroon, next-level supervisors received reports of new cases from village
      health workers during routine weekly visits to endemic villages. The Pakistan
      program established a faster case reporting scheme that allowed higher level
      personnel (sector supervisors and regional managers) to confirm cases within one
      week of worm emergence. Second, in Cameroon case containment activities were
      extended only to villages reporting five or more cases the previous transmission
      season and villages with recent confirmed cases. In Pakistan, all villages
      reporting cases during the previous year were included in the program. A village
      by-village case search one year after initiation of case containment in the Mayo
      Sava indicated decreases of 60% in the number of cases and 51% in the number of
      villages reporting cases. Based on the apparent success of the efforts in
      Cameroon, we propose a two-stage scheme for implementation of case containment.
      Both stages are based on rapid detection and containment of cases, within 24 hr
      of worm emergence, by village-based health workers. In stage 1, cases are
      reported and confirmed during routine weekly visits to the endemic villages by
      next-level supervisors. Weekly reporting should be extended to all villages with
      recent confirmed cases and to as many villages reporting cases during the
      previous transmission season as logistically possible.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7513133
TI  - Immunologic characterization of two monoclonal antibodies reactive with
      repetitive carbohydrate epitopes of circulating Schistosoma mansoni egg antigen.
AB  - A panel of 60 monoclonal antibodies (MAbs) reactive with repetitive epitopes of
      species-specific Schistosoma mansoni soluble egg antigen (SEA) was tested for
      performance in detecting circulating egg antigens. Two MAbs, 114-5B1-A and 114
      4D12-A, which were highly reactive with two different repetitive carbohydrate
      epitopes of soluble egg antigen, were found to detect circulating egg antigen in
      the sera of S. mansoni-infected mice. The two MAbs also showed strong reactivity
      with two high M(r) cercarial antigens present on the cercarial and schistosomular
      surface, while in the adult worms, antigens in the parenchyma were recognized. In
      two sandwich enzyme-linked immunosorbent assays (ELISA-5B1 and ELISA-4D12), each
      MAb was used as capture antibody and as conjugate, which resulted in assays with
      a lower detection level (0.2-0.4 ng) of the trichloroacetic acid-soluble fraction
      of soluble egg antigen (SEA-TCA)/ml. The antigen component(s) detected by ELISA
      5B1 and ELISA-4D12 were 10,000 and 40,000 times more concentrated in the egg
      antigen than in the adult worm antigen, respectively. With both assays, in serum
      of heavily S. mansoni-infected mice, antigen became detectable from eight weeks
      postinfection (PI) onwards, with a striking increase at nine weeks PI.

PMID- 7513134
TI  - Erythroid progenitors in the peripheral blood of children with sickle cell
      disease.
AB  - PURPOSE: The goals of this study were (a) to determine the number of peripheral
      blood burst forming units-erythroid (BFU-E); (b) to define the relationship
      between circulating BFU-E number and fetal hemoglobin (HbF) level; and (c) to
      define the relationship between BFU-E number and age in pediatric sickle cell
      disease (SCD) patients. PATIENTS AND METHODS: Fetal hemoglobin (HbF) level and
      peripheral blood BFU-E number were determined in children < 18 years of age with
      SCD in a steady state of their disease. These data were compared with those of
      normal children. RESULTS: An increased number of BFU-E was observed in the
      peripheral blood of children with SCD compared with normals (30.7 vs. 15.7 per
      10(5) mononuclear cells, respectively; p = 0.009). Overall there was the
      suggestion of a direct relationship between HbF level and peripheral blood BFU-E
      number (regression coefficient = 0.445; p = 0.06). Additionally, a strong inverse
      relationship between BFU-E number and age (regression coefficient = -0.671; p <
      0.0001) was observed. CONCLUSIONS: In children with SCD (a) there are an
      increased number of peripheral blood BFU-E compared with normal children; (b) the
      inverse relationship between HbF level and BFU-E number observed in adult SCD
      patients is not seen in children; and (c) there is a strong inverse relationship
      between age and BFU-E number. This information may help to further clarify the
      relationship between peripheral blood BFU-E and erythropoietic stress.

PMID- 7513135
TI  - A case-control retrospective study of the efficacy of granulocyte-colony
      stimulating factor in children with neuroblastoma.
AB  - PURPOSE: We conducted a retrospective case-control study to examine the effect of
      granulocyte-colony-stimulating factor (G-CSF) on the duration of the neutrophil
      nadir and other clinical parameters in children with neuroblastoma. PATIENTS AND
      METHODS: We retrospectively reviewed 85 courses of the same chemotherapy in 16
      consecutive neuroblastoma patients. The first nine patients received no growth
      factor and the following seven patients received G-CSF. Data obtained included
      days of neutropenia, fever rate and duration, hospitalization rate and duration,
      antibiotic duration, and infection rate. RESULTS: Patients who received G-CSF had
      a significant decrease in the period of neutropenia (mean 5.4 +/- 2.6 days per
      course vs. 11.4 +/- 4.1 days per course in the control group; p < 0.001). There
      were no statistically significant differences in episodes of fever per course,
      rate of hospitalization per course, duration of hospitalization, or duration of
      antibiotic therapy. Control patients had documented infections during 16% (nine
      of 56) of their chemotherapy courses, whereas the patients receiving G-CSF had
      infections during 7% (two of 29) of their courses, but this difference was not
      statistically significant (p = 0.318). We calculated that a study of 220 courses
      in each group would be needed to have adequate power to confirm that this
      difference is statistically significant. CONCLUSIONS: The administration of G-CSF
      in this patient population did result in fewer days of neutropenia, a finding
      that has been reported previously in several adult studies. However, we conclude
      that the clinical benefit of more rapid hematologic recovery in children remains
      uncertain and deserves further investigation in a large, prospective multicenter
      trial.

PMID- 7513136
TI  - Successful treatment of neutropenia in the hyper-immunoglobulin M syndrome with
      granulocyte colony-stimulating factor.
AB  - PATIENT: A young boy with hyper-immunoglobulin M (IgM) syndrome had recurrent
      severe infections, failure to thrive, and chronic neutropenia for 2 years despite
      treatment with i.v. gammaglobulin (IVIG). METHODS AND RESULTS: With the addition
      of granulocyte colony-stimulating factor (G-CSF; Filgrastim, Amgen, Inc.,
      Thousand Oaks, CA), increased doses of IVIG, and prophylactic trimethoprim
      sulfamethoxazole, his absolute neutrophil count increased from 0.64 x 10(9)/L to
      3.36 x 10(9)/L, and he has been free of significant infection for the past 22
      months. CONCLUSIONS: The use of G-CSF merits consideration in patients with hyper
      IgM syndrome and severe neutropenia.

PMID- 7513137
TI  - Increased cytokine levels and abnormal response of myeloid progenitor cells to
      granulocyte colony-stimulating factor in a case of severe congenital neutropenia.
      In vitro effects of stem cell factor.
AB  - PURPOSE: The cytokine levels and the in vitro granulopoiesis were studied to
      evaluate the mechanism of impaired granulopoiesis in severe congenital
      neutropenia (SCN). PATIENT AND METHODS: The patient was a 5-year-old boy with
      SCN. We assayed the colony-stimulating activity (CSA) produced by peripheral
      blood (PB) cells from the patient. The plasma levels of cytokines were measured
      using enzyme immunoassay. These included granulocyte colony-stimulating factor (G
      CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1
      alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-6, and tumor necrosis factor
      alpha. The effects of IL-3 and stem cell factor (SCF) on the proliferation of
      granulocyte-macrophage colony-forming cells (GM-CFCs) were studied. RESULTS: CSA
      produced by PB cells from the patient was almost the same as in the healthy
      control. The level of endogenous G-CSF was elevated to 334 pg/ml, and GM-CSF, IL
      2, IL-3, and IL-6 were slightly elevated. The numbers of GM-CFCs were markedly
      depressed in the presence of G-CSF alone and showed no increment on additional
      stimulation by IL-3. SCF in combination with G-CSF significantly augmented the
      proliferation of GM-CFCs. CONCLUSIONS: These findings suggest that some cytokines
      including G-CSF may be elevated in SCN patients and that CSF may play an
      important role in the pathogenesis of SCN.

PMID- 7513138
TI  - Positive response to granulocyte-colony-stimulating factor in dyskeratosis
      congenita before matched unrelated bone marrow transplantation.

PMID- 7513139
TI  - Significant inhibition of endothelial cell growth in tumor vasculature by an
      angiogenesis inhibitor, TNP-470 (AGM-1470).
AB  - Growth inhibition of tumor cells and vascular endothelial cells in M5076 tumors
      was examined following treatment with TNP-470 to elucidate its antitumor action.
      The bromodeoxyuridine-labeling index (LI) of tumor and endothelial cells was
      significantly decreased by TNP-470 treatment to 47 and 9% of the controls,
      respectively. The LI of endothelial cells was decreased earlier and more
      extensively than that of tumor cells. In contrast, the LI of endothelial cells
      was not decreased by treatment with chemotherapeutic agents, adriamycin and
      cisplatin, at the dose giving a similar growth inhibition on tumor cells. These
      results suggest that the antitumor action of TNP-470 is exerted by its
      angiogenesis inhibition.

PMID- 7513140
TI  - Intracellular expression of P-glycoprotein in a human colon tumor cell line.
AB  - A number of human tumor cell lines originating in tissues which normally express
      high levels of P-glycoprotein were examined for the expression of mdr-1 RNA and P
      glycoprotein and their sensitivity to doxorubicin and vincristine. There was a
      wide variation in expression levels and in drug sensitivity among the cell lines.
      In the human colon tumor cell line, LS 174T, high levels of P-glycoprotein and
      mdr-1 RNA were observed, but this line was very sensitive to doxorubicin and
      vincristine. Immunoprecipitation of P-glycoprotein from preparations of membrane
      and cytoplasmic proteins and immunofluorescence studies using anti-P-glycoprotein
      antibodies revealed that P-glycoprotein in these cells is not associated with the
      plasma membrane, but is, instead, found intracellularly. These results emphasize
      the need for functional analysis of P-glycoprotein in cells that express this
      mediator of multidrug resistance.

PMID- 7513141
TI  - Inhibitory effect of TNP-470, a new anti-angiogenic agent, on the estrogen
      induced rat pituitary tumors.
AB  - An angiogenic inhibitor, TNP-470, is an analogue of fumagillin. This study
      reports the effects of TNP-470 and bromocriptine on the normal pituitary glands
      and estrogen-induced rat pituitary tumors. TNP-470 inhibited the increase of
      normal pituitary weight and the tumorigenesis induced by estrogen. The decreased
      labelling index in the pituitary cells, showed that TNP-470 may suppress the
      activity of cell proliferation as the result of anti-angiogenesis. Combination
      treatment with TNP-470 and bromocriptine was much more effective than TNP alone.
      These results suggest that TNP-470 is a potentially beneficial drug for pituitary
      tumors.

PMID- 7513142
TI  - Development of tumorigenicity and rearrangement of chromosome 1 correlates with
      down-regulation of cell-surface glycoproteins in human mammary carcinoma cell
      line.
AB  - In the current study, attempts were made to identify any products of normal
      breast cell genes, that may become inactivated in the malignant counterparts.
      Using an immune-tolerization/immunization procedure of generating antibody, two
      different cell-surface glycoproteins termed luminal epithelial antigen, LEA.92
      and LEA.135 were identified. LEA.92 and LEA.135 expressions on MEC in a culture
      model-system, that reflect various steps of neoplastic transformation were
      detected on normal or immortalized MEC lines that were non-tumorigenic in nude
      mice. Furthermore, no rearrangement of chromosome 1 was observed in those cells.
      In contrast, both glycoproteins were undetectable on oncogenically transformed or
      established lines of mammary carcinoma cells that were tumorigenic. LEA.92 or
      LEA.135 negative cell lines exhibited a partial deletion of their chromosome 1.
      In tissue sections, LEA.92 expression was detected on the apical plasma membrane
      of normal and hyperplastic but not on the malignant mammary or extramammary
      epithelial cells (MEC). However, unlike LEA.92, LEA.135 was detected on certain
      cases of primary breast carcinoma cells, irrespective of morphological
      differentiation, in tissue sections.

PMID- 7513144
TI  - Tumor cell-selective flow cytometric analysis for DNA content and cytokeratin
      expression of clinical tumor specimens by "cross-gating".
AB  - A major problem with flow cytometric analysis of clinical solid tumor specimens
      is that of non-malignant cell contamination which contributes to inaccurate
      results. Monoclonal antibody to cytokeratin, a marker for epithelial tumor
      (carcinoma) cells, was successfully used in conjunction with a DNA-specific dye
      to dually stain specimens so as to obtain DNA profiles exclusively for marker
      positive tumor cells. This gating procedure was used also for analysis of the
      cell marker distribution for those cells having a DNA content consistent with
      aneuploidy. After successful verification in model systems, clinical carcinoma
      specimens were studied. The aneuploid population increased from a mean of 61%
      without gating to a mean of 81% with gating for cytokeratin. The cytokeratin
      positive cell fraction increased from a mean of 55% without gating to a mean of
      96% with gating for aneuploid DNA content. This gating procedure makes it
      possible to associate cell markers confidently with tumor cell populations, thus
      providing objective verification of the tissue of origin for these tumors. It can
      be performed simultaneously with standard gating for DNA analysis; and both
      procedures used together, cross-gating, are invaluable for more precise analysis
      of human tumor DNA and cell markers.

PMID- 7513143
TI  - Modulation of cisplatin resistance by 2'-deoxy-5-azacytidine in human ovarian
      tumor cell lines.
AB  - The sequential administration of 2'-deoxy-5-azacytidine (DAC) and cisplatin
      frequently results in synergistic cytotoxicity against human cancer cell lines
      (Frost P, et al Cancer Res 50:4572-4577, 1990) including the cisplatin resistant
      HEY ovarian cancer cell line. In this series of in vitro experiments the effect
      of DAC on cisplatin resistance was evaluated in two cisplatin resistant ovarian
      cell lines, C13* and A2780/DDP, and by varying the concentration ratio of DAC to
      cisplatin against the HEY cell line. For C13* and A2780/DDP sequential exposure
      to DAC and cisplatin resulted in synergy and a one to three-fold decrease in the
      concentration of cisplatin required to achieve defined levels of cytotoxicity.
      Augmentation of the synergistic interaction was also observed with the HEY line
      suggesting that increasing the concentration of DAC relative to cisplatin could
      result in improved modulation of cisplatin resistance for some highly cisplatin
      resistant lines. Since the concentrations of DAC and cisplatin required in vitro
      to observe these interactions are frequently achievable in human plasma, the
      clinical value of DAC modulation of cisplatin resistance could be tested in
      appropriately designed clinical trials.

PMID- 7513146
TI  - E-selectin and vascular cell adhesion molecule-1 are critical for initial
      trafficking of helper-inducer/memory T cells in psoriatic plaques.
AB  - BACKGROUND: To better understand local migration of inflammatory cells in
      psoriasis, we compared immunohistochemically the expression of cell adhesion
      molecules on endothelial cells of papillary microvessels, a subpapillary
      microvessel (SPMV), with the phenotypic profile of infiltrating T cells in
      initial, active, and involuting psoriatic lesions. RESULTS: Intercellular
      adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1)
      on papillary microvessel E-selectin and VCAM-1 on SPMV that had not been detected
      in normal/noninvolved skin were induced in psoriatic lesions. Intercellular
      adhesion molecule-1 on SPMV was constitutively expressed in normal/noninvolved
      skin and augmented in the degree of expression in psoriatic lesions.
      Intraepidermal and dermal angiocentric T cells in the initial and active lesions
      belonged predominantly to the CD3+, CD4+, CD45RO+, lymphocyte function-associated
      antigen-1+, and very late antigen-4+ helper-inducer/memory subset. The number of
      these memory T cells around SPMV was significantly correlated with the degree of
      expression of E-selectin and VCAM-1 on SPMV in the initial lesion. Intraepidermal
      memory T cells in the active lesion showed significant correlation with the
      expression of E-selectin and VCAM-1 on PMV. The CD8+ cells were dominant in the
      epidermis of the involuting phase. None of the adhesion molecules studied seemed
      to play a role in infiltration of this cell type. CONCLUSIONS: The results
      suggest (1) participation of memory T cells in the formation of the initial and
      active stages of psoriatic plaques, and (2) E-selectin and VCAM-1 on endothelium
      as the critical adhesion molecule for initial trafficking of memory T cells into
      psoriatic lesions.

PMID- 7513145
TI  - Effects of epidermal growth factor receptor blocking in cultured glioma
      spheroids.
AB  - A concentration as high as 1 microgram/ml of non-radioactive epidermal growth
      factor, EGF/was necessary to inhibit effectively the binding of 125I-EGF in
      glioma U-343MGaC12:6 cells. This concentration blocked the available EGF
      receptors within 30 minutes in monolayers, while 24 hour treatments were required
      in spheroids. The effects on growth, incorporation of radioactive thymidine, cell
      density and on extracellular pH were analysed in spheroids after exposure to 1
      microgram/ml EGF. The high EGF concentration did not significantly modify the
      growth curves for monolayers and small spheroids but increased the volume growth
      of large spheroids. The increase was partly due to lower cell density and partly
      to increased proliferation. The EGF treatment gave an increased incorporation of
      thymidine in spheroids, for at least up to 5 days after the administration, while
      no effect was seen in monolayers. The cell density decreased after the EGF
      treatment as seen from morphometric analysis in histological sections and by
      counting the number of cells per volume unit after trypsinization. The capacity
      to take up radiolabelled dextran increased, probably due to the decreased cell
      density. Other EGF-induced changes were also recognized, such as a reduction in
      extracellular pH by 0.1 units in the central regions of spheroids and an increase
      in intracellular pH by 0.47 units in analysed monolayer cells. The results showed
      that it is not possible to block the EGF-receptors without imposing changes in
      growth and metabolism.

PMID- 7513147
TI  - p53 immunostaining in dermatopathology.

PMID- 7513148
TI  - Omentopexy for tracheal autografts.
AB  - An effective method of vascularization is required in tracheal transplantation,
      as tracheal vessels are too find to be anastomosed easily. A series of
      experiments, including postmortem injection study, were conducted to assess the
      usefulness of omentopexy for tracheal autografts in 17 dogs. In group I (n = 4) a
      six-ring tracheal autograft was implanted in the greater omentum for 28 days. The
      structural integrity of all the autografts was maintained. In group II (n = 3) a
      six-ring cervical trachea was excised and reimplanted as an autograft without
      omental wrapping. All three autografts dissolved or transformed. No
      neovascularity from the recipient trachea or surrounding tissue was seen in the
      autografts by postoperative day 11. In group III (n = 10) omentopexy was added to
      the same experiment as group II. All the autografts were nourished adequately by
      the omental circulation as demonstrated by injection study, and remained viable
      early after transplantation. We conclude that the omentopexy is an effective
      method to facilitate neovascularization in tracheal autografts.

PMID- 7513149
TI  - Review of serologic testing for hepatitis C virus infection and risk of
      posttransfusion hepatitis C.
AB  - Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis and
      cirrhosis worldwide. Screening volunteer donors for antibody to HCV (anti-HCV)
      has reduced the risk of posttransfusion hepatitis C to less than 1.0% per
      recipient. Virtually all persons with acute HCV infection seem to become
      chronically infected, and an average of 67% acquire chronic liver disease with
      persistently elevated liver enzyme values. Among anti-HCV-positive blood donors,
      70% to 90% are HCV RNA positive, but less than half have biochemical evidence of
      liver disease. The extraordinarily high rate of persistent infection observed in
      humans and the lack of protection against rechallenge with homologous HCV strains
      demonstrated in experimental studies in chimpanzees suggest that HCV fails to
      induce an effective neutralizing antibody response. This raises major concerns
      for the development of effective passive or active immunoprophylaxis against
      hepatitis C.

PMID- 7513150
TI  - Temporal regulation of the IgE-dependent 1,2-diacylglycerol production by
      tyrosine kinase activation in a rat (RBL 2H3) mast-cell line.
AB  - We explored the possible role of tyrosine kinases in the IgE-dependent regulation
      of 1,2-diacylglycerol (DAG) production in RBL 2H3 cells. When triggered via their
      high-affinity IgE receptors (Fc epsilon RI), there was a rapid phosphorylation of
      tyrosine residues on a number of proteins. The phosphorylation of these proteins
      and ultimately histamine release were inhibited in a concentration-dependent
      manner by the tyrosine kinase inhibitor, tyrphostin. In cells labelled with
      [3H]myristic acid, we observed a characteristic biphasic increase in [3H]DAG
      production. In the presence of tyrosine kinase inhibitor, the initial increase in
      DAG was still observed, but the secondary increase, which was dependent on
      phosphatidylcholine-specific phospholipase D (PC-PLD) activation, was completely
      abolished. Tyrphostin significantly inhibited IgE-dependent activation of PC-PLD,
      suggesting that PC-PLD activation was regulated by tyrosine phosphorylation.
      Furthermore, when proteins from RBL 2H3 cells were immunoprecipitated with an
      anti-phosphotyrosine antibody, PC-PLD activity was recovered from the
      immunoprecipitated fraction. These results demonstrate that the secondary, but
      not the initial, phase of 1,2-DAG production in response to Fc epsilon RI
      aggregation is regulated by the initial activation of tyrosine kinases and that
      PC-PLD may be regulated directly by this mechanism.

PMID- 7513153
TI  - Recent trends in rifamycin research.
AB  - Rifamycin is a clinically useful macrolide antibiotic produced by the gram
      positive bacterium Amycolatopsis mediterranei. This antibiotic is primarily used
      against Mycobacterium tuberculosis and Mycobacterium leprae, causative agents of
      tuberculosis and leprosy, respectively. In these bacteria, rifamycin treatment
      specifically inhibits the initiation of RNA synthesis by binding to beta-subunit
      of RNA polymerase. Apart from its activity against the bacteria, rifamycin has
      also been reported to inhibit reverse transcriptase (RT) of certain RNA viruses.
      Recently, rifamycin derivatives have been discovered that are effective against
      Mycobacterium avium, which is associated with the AIDS complex. Consequently, the
      importance of and demand for rifamycin has increased tremendously, the world
      over. In this article, recent trends in rifamycin research and accessibility of
      recombinant DNA techniques to increase rifamycin production are reviewed.

PMID- 7513152
TI  - Subcellular localization and characterization of nitric oxide synthase(s) in
      endothelial cells: physiological implications.
AB  - Endothelial cells (EC) contain a constitutive Ca2+/calmodulin-dependent nitric
      oxide (NO) synthase (cNOS) which plays an important role in the local control of
      vascular tone. We compared the subcellular distribution of this enzyme in
      cultured and freshly isolated pig EC by determination of specific cNOS activity
      and immunoblot analysis. Similar studies were also performed with cultured and
      freshly isolated bovine and cultured human EC. Enzyme activity was predominantly
      (> 70%) associated with the particulate fraction of all EC types tested and was
      highest in freshly isolated porcine EC. Both specific cNOS activity and
      immunoreactivity were substantially higher (> 3-fold) in the microsomal as
      compared with the soluble fraction of all EC types tested. In freshly isolated
      pig EC, these two fractions also differed in terms of their Ca(2+)-dependency, pH
      optimum and inhibitor specificity. EC may thus contain either two different cNOS
      isoenzymes or a single enzyme, the conformation of which differs between the
      soluble and membrane-bound state. Moreover, detailed subcellular fractionation of
      freshly isolated pig EC revealed that the distribution of cNOS activity closely
      resembled that of the plasma membrane marker 5'-nucleotidase, suggesting that
      most, if not all, of the cNOS activity in these cells is associated with the
      plasma membrane. This localization might render the enzyme more susceptible to
      activation by physical stimuli, such as a shear stress-induced change in the
      fluidity of the plasma membrane. Moreover, the continuous exposure to shear
      stress in vivo may also upregulate cNOS expression in EC, since specific enzyme
      activity, immunoreactivity and basal NO release were significantly higher in
      freshly isolated EC as compared with cultured EC.

PMID- 7513151
TI  - Molecular analysis of Rh polypeptides in a family with RhD-positive and RhD
      negative phenotypes.
AB  - To investigate the genetic basis of the Rh polypeptide gene, we attempted the
      isolation of cDNA clones for Rh polypeptide from a family with the RhD-positive
      and RhD-negative phenotypes using the reverse transcription (RT)-PCR method for
      each reticulocyte RNAs followed by subcloning. The isolated cDNAs showed the
      existence of another Rh-related clone (RhPII-1 cDNA, tentative designation)
      besides the RhPI and RhPII cDNA clones reported previously by us. The RhPII-1
      cDNA had a single nucleotide substitution with one amino acid substitution
      compared with the RhPII cDNA:substitution C-->T in nucleotide 380, changing codon
      127 from GCG to GTG (Ala-->Val). The RhPI, RhPII, and RhPII-1 cDNA clones were
      detected in all individuals by the PCR experiment. This suggests that the Rh
      polypeptide genes have been inherited from parents and might be highly
      polymorphic. The PCR amplification of an RhPII-specific region from reticulocyte
      RNA and genomic DNA in all the family proved that the RhPII gene exists in both
      RhD-positive and RhD-negative individuals. By Southern-blot analysis of the DNAs
      from the family, two independent polymorphisms concerning the RhC/c and RhD/d
      phenotypes were observed. These results demonstrate that the RhPI and RhPII genes
      are also present in the RhD-negative donors, and the RhPII-related cDNAs encode
      not the RhD, but the RhC/c and/or E/e, polypeptides.

PMID- 7513154
TI  - cDNA and deduced amino acid sequence of a dwarf goat liver cytochrome P450
      fragment belonging to the CYP2C gene subfamily.
AB  - From a liver cDNA library derived from a phenobarbital treated dwarf goat a 1176
      bp cDNA-fragment, coding for 285 amino acids, has been isolated. Northern blot
      analysis reveals detection of a 2 kb mRNA which is inducible by phenobarbital,
      triacetyloleandomycin and to an lesser extent by beta-naphthoflavone. Analysis of
      the deduced amino acid sequence shows a 72.5% and a 71.1% homology with rabbit
      CYP2C3 and human CYP2C17, respectively. The nucleotide sequence reveals
      homologies of 79.8% and 78.7%, respectively. Comparison of the amino acid
      sequences between CYP2C forms of various species reveals a high homology around
      the Cys436, the so-called C-terminal cysteine containing peptide, which is
      assigned to be the heme-binding region.

PMID- 7513155
TI  - Regulation of inducible nitric oxide synthase mRNA levels by LPS, INF-gamma, TGF
      beta, and IL-10 in murine macrophage cell lines and rat peritoneal macrophages.
AB  - The molecular mechanisms of LPS, INF-gamma, TGF-beta, and IL-10 regulation of
      inducible nitric oxide synthase (iNOS) mRNA expression were evaluated. In murine
      macrophage cell lines, LPS-induced increases in iNOS mRNA were blocked by either
      cycloheximide or actinomycin D. Neither TGF-beta nor IL-10 alone had any effect
      on basal expression, and each only slightly reduced LPS induction of iNOS mRNA.
      However, IL-10 augmented INF-gamma induction of iNOS mRNA to very high levels,
      while TGF-beta inhibited INF-gamma induction. Human monocytes expressed no
      detectable iNOS mRNA with any stimuli, though Southern analysis on human genomic
      DNA revealed a specific human iNOS gene. In human macrophages, the iNOS gene may
      have become inoperative during evolution.

PMID- 7513156
TI  - Nitric oxide mediates suppression of cartilage proteoglycan synthesis by
      interleukin-1.
AB  - Slices of rabbit articular cartilage synthesized large quantities of nitric oxide
      (NO) following exposure to human recombinant interleukin-1 beta (hrIL-1 beta) or
      rabbit synovial cytokines (CAF). Each of these stimuli also strongly suppressed
      the biosynthetic incorporation of 35SO4(2-) into the glycosaminoglycans (GAGs) of
      cartilage proteoglycans. Treatment of cartilage fragments with L-NG
      monomethylarginine (L-NMA), a competitive inhibitor of NO synthase, both
      inhibited NO synthesis in response to IL-1 and CAF and restored proteoglycan
      synthesis. D-NMA was inactive in this regard, and L-arginine reversed the effects
      of L-NMA. S-nitrosylacetylpenicillamine (SNAP), an organic donor of NO,
      reversibly mimicked the effect of IL-1 and CAF on 35SO4(2-) incorporation. These
      data suggest that endogenously synthesized NO is the mediator which reduces
      cartilage proteoglycan synthesis in response to cytokines such as IL-1 and CAF.
      Antagonists of NO production may promote cartilage matrix synthesis and thus have
      potential as chondroprotective or chondroreparative agents.

PMID- 7513157
TI  - Pyrrolidine dithiocarbamate differentially affects interleukin 1 beta- and cAMP
      induced nitric oxide synthase expression in rat renal mesangial cells.
AB  - Inducible nitric oxide synthase (NOS) is expressed in renal mesangial cells in
      response to two principal classes of activating signals that interact in a
      synergistic fashion. These two groups of activators comprise inflammatory
      cytokines such as interleukin 1 (IL-1) or tumour necrosis factor alpha and agents
      that elevate cellular levels of cAMP. We have used pyrrolidine dithiocarbamate
      (PDTC), a potent inhibitor of nuclear factor kappa B (NF kappa B), to determine
      its role in IL-1 beta- and cAMP-triggered NOS expression. Micromolar amounts of
      PDTC suppress IL-1 beta-, but not cAMP-stimulated nitrite production, the stable
      end product of NO formation in mesangial cells. Furthermore, PDTC completely
      inhibited the increase of NOS mRNA in response to IL-1 beta, while only
      marginally affecting cAMP-induced NOS mRNA levels. Our data suggest that NF kappa
      B activation is an essential component of the IL-1 beta signalling pathway
      responsible for NOS gene activation and that cAMP triggers a separate signalling
      cascade not involving NF kappa B. These observations may provide a basis for the
      synergistic stimulation of NOS expression by cytokines and cAMP in mesangial
      cells.

PMID- 7513158
TI  - Insulin and glucocorticoids regulate IGFBP-1 expression via a common promoter
      region.
AB  - Hepatic expression of insulin-like growth factor binding protein-1 is regulated
      by insulin and glucocorticoids. To study underlying mechanisms, rat hepatocytes
      in primary culture were transfected with deletion mutants and heterologous
      promoter constructs, identifying a 41 bp region of the rat insulin-like growth
      factor binding protein-1 promoter which is sufficient to mediate regulation by
      both insulin and glucocorticoids. Half maximal suppression of promoter activity
      by insulin occurred at a physiologic concentration, 5 x 10(-10) M, and regulation
      by insulin was dominant in that insulin suppressed promoter activity at all
      dexamethasone concentrations. Transfection of rat hepatocytes in primary culture
      should be a useful approach for exploring the regulation of gene expression by
      insulin.

PMID- 7513159
TI  - The angiotensin II AT1 receptor is tyrosine and serine phosphorylated and can
      serve as a substrate for the src family of tyrosine kinases.
AB  - Angiotensin II AT1 receptor signal transduction has recently been shown to
      function through the phospholipase C isozyme, PLC-gamma. Since PLC-gamma is known
      to interact with phosphotyrosine containing proteins through SH2 domains, we
      examined the phosphorylation state of the AT1 receptor. Immunoprecipitation of
      the [32P] labeled AT1 receptor from rat aortic smooth muscle cells followed by
      alkali hydrolysis demonstrated the presence of tyrosine phosphorylation.
      Phosphoamino acid analysis of the excised bands demonstrated the presence of
      phosphoserine and phosphotyrosine residues. A fusion protein comprising the
      intracellular tail of the AT1 receptor was used to screen for candidate kinases,
      and the src kinase family displayed high activity. In summary, this study shows
      that the AT1 receptor is serine and tyrosine phosphorylated in vivo and suggests
      that a soluble kinase related to the src family may be responsible for the
      tyrosine phosphorylation.

PMID- 7513161
TI  - Cloning of the cDNA for the deleted syk kinase homologous to ZAP-70 from human
      basophilic leukemia cell line (KU812).
AB  - Syk kinase is one of the protein tyrosine kinases and forms a family with ZAP-70.
      We isolated two different sized cDNA clones of syk (Syk11 and Syk41) from a cDNA
      library of human KU812 (human basophilic leukemia cell line). The obtained two
      clones carried different messages, that Syk41 had a 69 bp-long insertion between
      the SH2 domain and the kinase domain compared with Syk11. Alignment of the two
      human syk predicted polypeptides with those of the porcine syk and ZAP-70
      revealed that human syk was 5 amino acid longer than the porcine syk at the N
      termini and that the insertion of the 23 amino acid found in Syk41 was present in
      the porcine syk and absent in ZAP-70. Reverse transcribed polymerase chain
      reaction targeting this region showed that both forms of the polyA RNA were
      expressed in Jurkat cells, human peripheral leukocytes and also KU812 cells and
      that the inserted form was dominant.

PMID- 7513160
TI  - Uromodulin (Tamm-Horsfall protein) is a leukocyte adhesion molecule.
AB  - Uromodulin (Tamm-Horsfall protein), the most abundant constituent of human urine,
      is synthesized exclusively in the kidney tubular epithelium and its amino acid
      sequence suggests a capacity for cell adhesion. We investigated adhesion between
      human uromodulin and neutrophils by allowing uromodulin, immobilized on
      microtiter plates, to interact with neutrophils. It was found that neutrophils
      attached to uromodulin in a saturable manner. The binding was inhibited by
      uromodulin in solution. It required metabolically active cells, was calcium
      sensitive and could be inhibited by arginine-glycine- aspartate-containing
      peptides in solution. These data suggest that uromodoulin can act as a specific
      ligand for neutrophils. This interaction is potentially important in leukocyte
      trafficking in the kidney and in the pathogenesis of interstitial nephritis.

PMID- 7513162
TI  - Interleukin-8 production by CD16-CD56bright natural killer cells in the human
      early pregnancy decidua.
AB  - Decidual CD16-CD56bright natural killer (NK) cells were sorted from the decidual
      mononuclear cells (MNC) at the early pregnancy using a fluorescence activated
      cell sortor. The CD16-CD56bright NK cell population occupies a major population
      in the decidual MNC, in contrast to a very small population (< 1%) in the
      peripheral blood MNC. These decidual CD16-CD56bright NK cells produced a large
      amount of IL-8, i. e., mean of 96.7 +/- 19.8 ng/ml in the 24 hr-cultured
      supernatants without any stimulant, which was comparable to the IL-8 production
      by LPS-stimulated peripheral blood MNC. Most of the IL-8 was ascribable to the
      production from decidual CD16-CD56bright NK cells. Intracytoplasmic IL-8 in the
      decidual CD56bright NK cells was also detected by flow cytometry. RT-PCR methods
      confirmed IL-8 mRNA expression in this population, while no or very scarce
      expression of IL-1 alpha and IL-1 beta mRNA was observed. The present study is a
      first observation revealing that decidual CD16-CD56bright NK cells express IL-8
      mRNA and produce IL-8.

PMID- 7513163
TI  - Identification of an alternatively spliced form of the murine homologue of B7.
AB  - B7 on antigen presenting cells is a costimulatory ligand necessary for full
      activation of T cell. Receptors for B7 have been known as CD28 or CTLA4. We here
      show that in addition to B7 mRNA, an alternatively spliced mRNA (designated as
      MB7-2 mRNA), that immunoglobulin (Ig)C-like domain coded by exon 3 has been
      spliced out, is found in activated murine splenic B cells by reverse
      transcriptase-polymerase chain reaction analysis. Chinese hamster ovary (CHO)
      cells transfected with MB7-2 bound CTLA4Ig less well than those expressing B7,
      but bound CD28Ig to a similar extent, indicating that IgV-like domain contains
      the complete binding site for CD28. In addition, IgC-like domain may participate
      in an increase in the affinity for CTLA4. Thus, MB7-2 represents a new form of
      the murine B7 with different receptor binding properties.

PMID- 7513165
TI  - Tyrosine phosphorylation of Shc is induced by IL-3, IL-5 and GM-CSF.
AB  - The receptors for IL-3, IL-5 and GM-CSF belong to the hematopoietic receptor
      superfamily and have no intrinsic tyrosine kinase activity but nevertheless
      indirectly induce protein tyrosine phosphorylation. In order to directly compare
      the effects of IL-3, IL-5 and GM-CSF on protein tyrosine phosphorylation we
      analyzed the murine cell line FDCP-1 which proliferates equally well in response
      to IL-3 and GM-CSF and the cell line B13 which responds to both IL-3 and IL-5.
      The protein tyrosine phosphorylation pattern induced by IL-3, IL-5 and GM-CSF in
      these cell lines was shown to be remarkably similar and all three cytokines
      induced tyrosine phosphorylation of Shc, a src homology domain-2 containing
      protein which has been shown to be involved in Ras activation by tyrosine kinase
      receptors.

PMID- 7513164
TI  - Involvement of type 2C phosphatase in the dephosphorylation of 26 kDa
      phosphoprotein in rat parotid acinar cells.
AB  - Phosphorylation of three particulate proteins with molecular masses of 34, 26,
      and 22 kDa was stimulated in the presence of cyclic AMP/3-isobutyl-1
      methylxanthine in saponin-permeabilized rat parotid acinar cells. When the
      particulate fraction isolated from the cells labeled with [gamma-32p]ATP was
      incubated at 30 degrees C, dephosphorylation of the 26 kDa phosphoprotein
      occurred in the presence of Mg2+ or Mn2+. Okadaic acid had no effect on the
      Mg(2+)-dependent dephosphorylation of the 26 kDa phosphoprotein. Addition of the
      recombinant type 2C phosphatase, Mg(2+)-dependent and okadaic acid-insensitive
      phosphatase, caused a remarkable dephosphorylation of the 26 kDa phosphoprotein.
      These observations strongly suggest type 2C phosphatase is involved in the
      dephosphorylation of the 26 kDa phosphoprotein.

PMID- 7513166
TI  - Effects of cytokines and growth factors on phosphorylated fetuin biosynthesis by
      adult rat hepatocytes in primary culture.
AB  - Recently, we showed that a 59 kDa non-phosphorylated sialoprotein purified from
      rat bone matrix is the rat counterpart of bovine fetuin and human alpha 2-HS
      glycoprotein and that fetuin synthesized and secreted by adult rat hepatocytes in
      primary culture is mostly phosphorylated (phosphofetuin), though fetuin is known
      to contain no phosphorus. Here we report that the rate of synthesis of
      phosphofetuin by hepatocytes in culture was reduced by inflammatory cytokines
      such as human interleukin (hIL)-6, human tumor necrosis factor-alpha and hIL-1
      alpha, but dose-dependently stimulated by growth factors of hepatocytes, such as
      hepatocyte growth factor (HGF)/scatter factor (SF), epidermal growth factor and
      insulin, as determined by metabolic labeling and Northern blot analysis using
      cDNA for rat fetuin as a probe. We also showed that administration of HGF/SF
      stimulated gene expression of rat fetuin in vivo.

PMID- 7513167
TI  - [Affinity chromatography of proteinases].
AB  - Studies on the affinity chromatography of proteinases as the most efficient
      approach to their separation are reviewed. The paper contains discussion of the
      methods used to prepare affinity sorbents by attaching gramicidin and bacitracin
      to various supports. The two cyclopeptides contain amino acid residues, meeting
      specificity requirements of proteinases of various classes, these materials thus
      being affinity sorbents of general type. Rules governing the interaction of
      proteinases with these sorbents are discussed, along with numerous examples of
      their chromatography on sorbents of general type as well as on more specific
      sorbents adapted to the separation of particular types of proteinases. Sorbents
      containing benzylsuccinic, benzylmalonic and phenylboronic acid residues are
      considered in details.

PMID- 7513168
TI  - Protective cross-reactive epitope on the nonstructural protein NS1 of influenza A
      virus.
AB  - We reported previously that adoptive immunization with an influenza A virus NS1
      specific H-2Ld-restricted, cross-reactive, CTL clone A-11 established by
      stimulation with A/PR/8/34 virus (H1N1) reduced lung virus titers in mice
      challenged with virus in vivo (Virology 178:174-179, 1990). Using a set of
      recombinant vaccinia virus constructs containing truncated portions of the NS
      gene we have localized this cross-protective CTL epitope to the N-terminal region
      of the NS1 protein. This region of NS1 is active in inducing CD8+ CTL in vivo
      because virus-stimulated BALB/c immune spleen cells in bulk cultures also
      recognized the N-terminal region of the NS1 protein.

PMID- 7513169
TI  - Enhancement of fish mortality by rhabdovirus infection after immunization with a
      viral nucleoprotein peptide.
AB  - A similar sequence to a mouse immunodominant CTL peptide (SYVLQGN, single-letter
      amino acid code, conserved amino acids underlined) identified in the
      nucleoproteins of several strains of vesicular stomatitis virus (VSV) (37) was
      found in the nucleoproteins of viral hemorrhagic septicemia virus (VHSV) of
      salmonid fish (GYVYQGL in VHSV 07.71 and GYVYQGS in VHSV Makah) and not in the
      nucleoproteins of other rhabdoviruses. The in vivo immunization of fingerling
      salmonid fish (rainbow trout Onchorynchus mykiss, W) with this VHSV peptide and
      their subsequent challenge with VHSV resulted in the enhancement rather than in
      the reduction of fingerling trout mortality. Possible implications for the
      development of subunit vaccines against VHSV are discussed.

PMID- 7513170
TI  - First trimester biochemical screening for Down's syndrome.
AB  - A number of biochemical markers in maternal serum have been proposed for first
      trimester screening for Down's syndrome. The most promising four are pregnancy
      associated plasma protein A (PAPP-A), the free beta sub-unit of human chorionic
      gonadotrophin (hCG) (free beta glycoprotein sub-unit), unconjugated oestriol
      (uE3) and alpha-fetoprotein (AFP). An analysis of the published literature
      suggests that 70% of affected pregnancies could be detected for a 5% false
      positive rate if the four markers are used in combination with maternal age and
      assumed to be independent measures of risk. This is a level of performance that
      is similar to second trimester screening. It is, however, a tentative estimate
      because of the assumption of independence and the possibility that the effect may
      be exaggerated by publication bias. Further research is needed before such
      screening is introduced. Other first trimester markers which have been studied
      include total hCG, free alpha-hCG, CA125, PLAP and SP1 but they either look
      unpromising or there are too few data available to determine their value. The
      timing of antenatal diagnosis by means of chorion villus sampling should be
      delayed until after 10 weeks of pregnancy because of the risk of causing limb
      defects. Screening need not, therefore, be performed before about 9 or 10 weeks
      of pregnancy.

PMID- 7513172
TI  - Amylase in lung carcinomas. An ultrastructural and immunohistochemical study of
      two adenocarcinomas, and a review of the literature.
AB  - The ultrastructure of two lung adenocarcinomas with immunohistochemical and
      biochemical expression of amylase is reported. Isoenzyme determination performed
      on tumour tissue showed a salivary-type amylase. None of the carcinomas was
      associated with hyperamylasaemia. Ultrastructurally, the adenocarcinomas
      contained a varying number of heterogeneous granules resembling lysosomes. None
      of the tumours contained mature zymogen granules. The findings are discussed in
      relation to previous cases of amylase-containing lung carcinomas subjected to
      electron microscopy. The vast majority of these carcinomas were associated with a
      significant elevation of serum amylase. Various theories which might explain the
      absence of hyperamylasaemia in the presented cases are proposed. The biological
      and diagnostic significance of amylase production is discussed.

PMID- 7513173
TI  - An estimation of the dietary intake of pesticide residues in Italy from survey
      data.

PMID- 7513174
TI  - A need for community education, popular participation and intersectoral action to
      develop and sustain water and sanitation programmes.

PMID- 7513171
TI  - Acute kidney graft rejection. A morphological and immunohistological study on
      "zero-hour" and follow-up biopsies with special emphasis on cellular infiltrates
      and adhesion molecules.
AB  - Serial biopsies from 41 consecutive renal allotransplanted patients were
      evaluated in order to obtain pretransplant data as well as information on well
      functioning and acutely rejecting grafts. Each patient served as his own control.
      Thirty-five patients were followed according to the schedule which included
      biopsy prior to transplantation, shortly after opening of reanastomosis, at least
      once postoperatively (days 7-10), and furthermore whenever clinically indicated.
      The morphological evaluation was in each case combined with immunofluorescence
      (to detect immunoglobulins and complement fractions) and immunohistochemistry
      with a wide panel of monoclonal antibodies for T cells (CD2, CD3, CD4, CD8, gamma
      delta), B cells (CD20, CD22), macrophages (CD68, MAC387) NK cells (leu-7, CD16),
      activation markers (IL-2-R, Ki-67, transferrin-R), MHC antigens (HLA-ABC, HLA
      DR), adhesion molecules (ICAM-1, VCAM-1, ELAM-1, PADGEM, VLA-4, LFA-1
      alpha/beta), and growth factors (EGF, TGF-alpha, EGF-R). When 132 biopsies and 10
      failed allografts were examined, no specific morphological or immunohistological
      parameter predictive of rejection or graft outcome could be found. Morphology in
      follow-up biopsies from non-rejecting and rejecting patients revealed a continuum
      of inflammatory changes, and several non-rejecting cases demonstrated cellular
      inflammatory infiltrates which could not be discriminated from those seen in
      acute rejection. Of the patients 44% had acute rejection accompanied by increased
      infiltration of T cells and macrophages showing enhanced IL-2-R expression,
      increased tubular and endothelial staining for MHC class II, ICAM-1, and VCAM-1,
      and strong leukocytic expression of VLA-4 and LFA-1 alpha/beta.

PMID- 7513175
TI  - [Chlamydia infections and possibilities for prevention].

PMID- 7513176
TI  - [Consumption of biologically active substances from non-alcoholic beverages. II.
      Fluoride consumption in a group of young people].

PMID- 7513177
TI  - [Vaccination against hepatitis B. The 1988-1991 experience at Local Health
      District 9, Lombardy].

PMID- 7513178
TI  - [Evaluation of coronary risk. General concepts].

PMID- 7513179
TI  - Neurofilament function and dysfunction: involvement in axonal growth and neuronal
      disease.
AB  - Neurofilaments make up the major intermediate filament system in mature neurons.
      Recent studies demonstrate that neurofilaments in vivo are obligate
      heteropolymers and are required for proper radial growth of axons. Furthermore,
      forced over-expression of neurofilament subunits in transgenic mice shows that
      abnormal accumulation and assembly of neurofilaments, similar to that commonly
      found in human motor neuron disease can directly cause motor neuron dysfunction.

PMID- 7513180
TI  - Dielectric spectroscopy of mammalian cells. 2. Simultaneous in situ evaluation by
      aperture impedance pulse spectroscopy and low frequency dielectric spectroscopy
      of the biomass of HTC cells on Cytodex 3.
AB  - Low-frequency dielectric spectroscopy has been used in situ, i.e. while the cells
      are still attached to their microsupport, to monitor the changes of biomass
      accompanying the growth of anchorage-dependent cells. This method, when compared
      to Aperture Impedance Pulse Spectroscopy (also called electronic sizing), is
      characterized by a somewhat lower degree of resolution. Suggestions are made on
      how to determine the capacitance of the spent growth medium alone, still keeping
      the probe inserted in the bioreactor. This will make dielectric spectroscopy the
      first truly in situ, on-line, in real time, non-invasive measure of the biomass.

PMID- 7513182
TI  - Dengue in the Americas. An update.

PMID- 7513181
TI  - Growth of human vascular endothelial cells on various types of microcarriers.
AB  - Various types of microcarriers were tested as growth substrate for the
      cultivation of either endothelial cells from human umbilical cord veins or of
      EA.hy926, an immortalized cell line of endothelial origin. Cell growth was tested
      on microcarriers in tissue culture flasks and spinner flasks. Solid (Cytodex type
      I, II, III, Gelibeads, Mica) and macroporous (Polyhipe, CultiSpher GL, PolyporE
      type I) microcarriers were tested. For the solid carriers the best results were
      obtained with Mica and for the macroporous carriers with CultiSpher GL.

PMID- 7513183
TI  - The role of GM-CSF and G-CSF in stem cell transplantation.

PMID- 7513184
TI  - Are we obtaining the maximum benefit from GM-CSF and G-CSF?

PMID- 7513185
TI  - Lung transplantation for mechanically ventilated patients.
AB  - As lung transplantation has become more successful, the selection criteria have
      broadened; however, some relative contraindications to lung transplantation are
      controversial. Some programs consider mechanical ventilation to be a major
      contraindication to lung transplantation because airway colonization with
      bacteria may lead to nosocomial infection and respiratory muscle deconditioning
      may necessitate prolonged postoperative ventilatory support. We report our
      experience of seven double lung transplant procedures on six patients requiring
      mechanical ventilation. Five patients with cystic fibrosis required preoperative
      mechanical ventilation for 7 to 19 days (mean, 10.7 days). One patient with acute
      lung injury required 115 days of preoperative mechanical ventilatory support.
      Only the latter patient required prolonged (27 days) postoperative mechanical
      ventilation because of respiratory muscle weakness; the others were extubated in
      1 to 19 days (mean, 7.8 days). No early complications related to bacterial
      infection were seen. Two patients required temporary hemodialysis for transient
      kidney failure. Three patients had postoperative neurologic residua; one patient
      had a transient hemiparesis, and seizures developed in two patients. One patient
      died 3 months after transplantation from severe central nervous system
      complications with no evidence of pulmonary problems; and two patients died 17
      months after transplantation, one of them receiving a second double lung
      transplant for obliterative bronchiolitis. Except for the patient who required
      prolonged preoperative ventilatory support, mechanical ventilation did not appear
      to play a role in the outcome of these patients. The posttransplantation hospital
      stay and hospital charges for patients requiring pretransplantation ventilatory
      support were not significantly different from those for other lung transplant
      recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513186
TI  - Improved long-term graft outcome in lung transplant recipients who have donor
      antigen-specific hyporeactivity.
AB  - We have shown that in renal transplant recipients the development of in vitro
      donor antigen-specific hyporeactivity correlates with improved long-term graft
      outcome. Donor antigen-specific hyporeactivity is determined by in vitro mixed
      lymphocyte culture assays with recipient cells used as responder cells and
      homozygous typing cells as stimulator cells. Hyporeactivity is defined as a
      decreased response to stimulation by specific homozygous typing cells that define
      donor antigens, whereas response to homozygous typing cells defining third-party
      antigens remains unchanged. We tested 23 lung transplant recipients at least 1
      year after transplantation to determine if donor antigen-specific hyporeactivity
      and the corresponding improved graft outcome were organ specific. Of these 23
      recipients, eight had donor antigen-specific hyporeactivity; they demonstrated a
      trend toward a lower incidence of late acute rejection episodes (one rejection
      episode in one patient) versus the 15 recipients who remained responsive to donor
      antigens (11 rejection episodes in six patients). No recipients with donor
      antigen-specific hyporeactivity have been diagnosed with obliterative
      bronchiolitis, unlike six recipients who remained responsive to donor antigens
      (0% versus 40%; p = 0.058). We conclude that immune regulation, as evidenced by
      donor antigen-specific hyporeactivity, correlates with improved graft outcome for
      lung transplant recipients and may even provide immunologically based criteria
      for selecting candidates whose immunosuppression might be reduced successfully.

PMID- 7513187
TI  - Characterization and partial purification of the VDAC-channel-modulating protein
      from calf liver mitochondria.
AB  - The mitochondrial channel, VDAC, mediates metabolic flux across the mitochondrial
      outer membrane. When reconstituted into planar phospholipid membranes, VDAC is
      voltage-dependent, existing in multiple conformational states with different
      selectivities and permeabilities. At low membrane potentials, these channels are
      in the open state and are anion-selective. VDAC channels switch to lower
      conductive closed states at high membrane potentials. The VDAC modulator, a
      soluble mitochondrial protein, has been demonstrated to dramatically increase the
      voltage dependence of VDAC channels and induce the channels to enter closed
      states even at low membrane potentials. We have isolated and partially purified
      this modulating protein and the activity is associated with a 54 kDa protein on
      SDS-PAGE. Under native reduced conditions the activity eluted around 100 kDa from
      a gel filtration column. As little as 200 ng/ml of the partially purified protein
      was sufficient to modulate reconstituted VDAC channels. This protein had a pI of
      5.1. A second activity with a pI of 4.8 was far more potent, making VDAC-channel
      containing membranes virtually non-conductive in some experiments. The effects of
      both modulator activities could be completely reversed by the addition of
      pronase. Simple perfusion of the chamber did not reverse the effect of the
      modulator on VDAC. By controlling the gating of VDAC channels, the VDAC modulator
      could play an important role in regulating cellular metabolism.

PMID- 7513188
TI  - Staging toward the Fontan operation.

PMID- 7513189
TI  - Neonatal palliative switch for complex univentricular heart.

PMID- 7513190
TI  - N-acetylneuraminic acid estimation in human serum by neuraminidase and
      resorcinol/ferric(III) chloride reagent in hydrochloric solution.
AB  - By the method described the serum concentration of the protein-bound or the total
      N-acetylneuraminic acid can be determined. The estimation of the protein-bound N
      acetylneuraminic acid is a specific method. In comparison to the Arzneibuch
      (D.L.) GDR-method (Vol. 2, Akademie Verlag Berlin, 1985) based on Svennerholm
      (Biochim. Biophys. Acta 24 (1957) 604-611) the advantages of our estimation are:
      high stability of the dye complex during a period of at least one hour for a
      final concentration of at least 6.0 mol/l hydrochloric acid; omission of the time
      consuming resuspension of the protein precipitation and the extraction of the dye
      product with n-amyl alcohol; and the lack of diminution of the monosaccharide
      influence.

PMID- 7513193
TI  - Mutations in the Fas antigen gene in lpr mice.
AB  - The Fas antigen is a cell surface protein belonging to the tumor necrosis
      factor/nerve growth factor receptor family and it mediates apoptosis. The Fas
      antigen gene is the structural gene for the mouse mutation, lpr
      (lymphoproliferation). In one allele of lpr, an early transposable element (a
      mouse endogenous retrovirus) is inserted into an intron of the Fas antigen gene,
      which causes premature termination and aberrant splicing of the Fas antigen
      transcript. In the other allele (lprcg), a point mutation in the signal
      transducing domain of the cytoplasmic region abolishes the function of the Fas
      antigen.

PMID- 7513191
TI  - Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective
      disorder.
AB  - Levels of norepinephrine (NE), serotonin (5-HT), dopamine (DA), and their major
      metabolites were determined in postmortem brain obtained from nine subjects with
      antemortem histories meeting DSM-III-R criteria for bipolar affective disorder.
      Compared with controls, no statistically significant differences were found in
      mean levels of NE, 5-HT, or DA in any brain area of bipolar subjects. NE turnover
      as estimated by the ratio of the major NE metabolite, 3-methoxy-4
      hydroxyphenylethyleneglycol (MHPG) to NE was increased in frontal (+107%),
      temporal (+103%), and occipital (+64%) cortex and thalamus (+83%). Significant
      decreases were found in the major 5-HT metabolite 5-hydroxyindoleacetic acid (5
      HIAA), in frontal (-54%) and parietal cortex (-64%), and in 5-HIAA/5-HT ratio in
      temporal cortex (-55%), with a trend for decreases in both measures in caudate
      nucleus. In addition, levels of the major DA metabolite, homovanillic acid (HVA)
      were significantly decreased (-46%) in parietal cortex and HVA/DA ratios were
      significantly reduced (-66%) in occipital cortex obtained from bipolar compared
      to control subjects. Our data, taken together with previous findings regarding
      monoamines in postmortem brain of depressed and suicide subjects, suggest that
      decreased 5-HT metabolite levels and turnover may be common to all mood
      disorders. Increased cortical NE turnover, however, may be a more important
      component in the pathophysiology of bipolar disorder.

PMID- 7513194
TI  - MRL-lpr/lpr disease: theories meet Fas.
AB  - It has been exciting for scientists to postulate all sorts of derangements to
      explain the numerous observations regarding the disease of MRL-lpr/lpr mice.
      Until recently, our imaginations have had almost free reign, unconstrained by any
      true knowledge. Now, however, it has been found that the lpr gene represents a
      mutation which causes a defect in a cell surface molecule, Fas. Since the normal
      Fas is thought to be important in programmed cell death, apoptosis, the lpr
      associated defect in Fas is thought to interfere with normal apoptosis.
      Therefore, we are forced to reconsider all hypotheses regarding lpr/lpr mice in
      terms of a defect in Fas. This paper represents such an attempt. It suggests that
      failure of peripheral apoptosis of CD4+ cells allows self-reactive helper T cells
      to persist and drive autoantibody production. Failure of apoptosis of self
      reactive CD8+ cells leads to down-regulation of CD8 and persistence as CD4-, CD8-
      T cells which contribute to the lymphadenopathy.

PMID- 7513192
TI  - Porcine ovarian granulosa cells secrete insulin-like growth factor-binding
      proteins-4 and -5 and express their messenger ribonucleic acids: regulation by
      follicle-stimulating hormone and insulin-like growth factor-1.
AB  - Using ligand blotting, Western immunoblotting, and Northern analysis, we have
      characterized the insulin-like growth factor (IGF)-binding proteins (IGFBPs)
      produced by cultures of porcine granulosa cells. Ligand blot analysis of
      conditioned medium from untreated cultures of moderately differentiated granulosa
      cells (MDGCs; from 4-6-mm follicles) revealed mainly IGF-binding activity
      associated with IGFBP-2 (34 kDa) and IGFBP-3 (40/44-kDa doublet), which have
      previously been identified and characterized. In addition, these cultures
      secreted 30- and 22-kDa forms under some circumstances. The identification and
      regulation of these IGFBPs of lower molecular mass were the focus of the current
      studies. Treatment of these MDGCs with IGF-I dramatically stimulated the
      production (to a detectable level) of a 30-kDa IGFBP that was identified by
      immunoblotting with antiserum to IGFBP-5 but not antisera to IGFBP-1, -2, -3, -4,
      or -6. Production of IGFBP-5 was attenuated by concurrent treatment with FSH.
      IGFBP-5 mRNA in these cultures was correspondingly stimulated by IGF-I but
      unaffected by FSH. FSH increased the level of a minor 22-kDa IGFBP. Messenger
      RNAs for IGFBP-1, -4, and -6 were also examined but only IGFBP-4 mRNA was
      detectable, suggesting that the 22-kDa band was IGFBP-4. These results were
      compared to those in cultures of immature granulosa cells from 1-3-mm follicles,
      in which 22- and 30-kDa IGFBPs were readily detectable. An antiserum to IGFBP-4
      precipitated the 22- and 30-kDa bands whereas deglycosylation shifted the 30-kDa
      IGFBP to 22 kDa, suggesting that both these bands represent glycosylation
      variants of IGFBP-4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513196
TI  - Discovery of novel hematopoietic cell adhesion molecules from human bone marrow
      stromal cell membrane protein extracts by a new cell-blotting technique.
AB  - In an attempt to define the role of cell adhesion molecules (CAMs) within the
      bone marrow (BM) microenvironment in normal hematopoiesis and in leukemia
      development, a novel cell-blotting technique that involved cell adhesion to
      protein bands after separation by lithium dodecyl sulfate-polyacrylamide gel
      electrophoresis (LDS-PAGE) and blotting onto polyvinylidene difluoride (PVDF)
      membrane has been developed. Human BM stromal cell membrane fractions have been
      prepared from Dexter-type cultures after cell lysis by sonification and
      differential centrifugations of the sonification contents. The 20,000 g pellets
      representing membrane fractions have been solubilized by 2% Triton X-100, 0.575%
      LDS, and 8 mol/L urea in sequential order. The protein extracts are fractionated
      by LDS-PAGE and screened for CAMs by the new cell-blotting technique. This led to
      identification of nine protein bands in lanes containing LDS extracts showing
      adhesion of KG1a (CD34+ progenitor myeloid) cells. Evidence that the BM proteins
      exhibiting KG1a cell adhesion are novel CAMs is based on the observations that
      these proteins, in comparison with known CAMs, specifically VCAM-1, CD54, and
      CD44, show (1) contrasting detergent-solubility properties, (2) different
      temperature requirement for mediating cell adhesion function, and (3) markedly
      distinct electrophoretic mobilities. The various cell types tested, notably KG1a,
      NALM-6, WIL-2, Ramos, HS-Sultan, K562, JY B lymphoblastoid cells, and T
      lymphoblasts, showed distinctive patterns of binding to different subsets of BM
      CAMs. These results demonstrate a new approach to studies of molecular mechanisms
      that may determine specificity of hematopoietic cellular localization within BM
      microenvironment and may play an important role in controlling hematopoiesis.

PMID- 7513197
TI  - Thy-1 expression is linked to functional properties of primitive hematopoietic
      progenitor cells from human umbilical cord blood.
AB  - We have previously shown that the most primitive human hematopoietic cells are
      included within a cell subpopulation expressing high levels of CD34 and low or
      undetectable levels of CD45RA and CD71. In this study, cord blood cells with this
      phenotype were sorted and further separated based on their expression on the Thy
      1 antigen. The proliferation and differentiation of the purified cell fractions
      in response to a mixture of hematopoietic cytokines was analyzed in serum- and
      stroma-free liquid cultures. Thy-1+ cells (25% of CD34+ CD45RAlo CD71lo cells)
      were particularly enriched for high proliferative potential colony-forming cells
      (HPP-CFC; up to 45% of the clonogenic cells), whereas Thy-1- cells were enriched
      for multipotential colony-forming cells (CFU-MIX; up to 46% of the clonogenic
      cells). When both subpopulations were cultured in serum-free liquid cultures
      supplemented with a cytokine mixture that included steel factor, interleukin-6
      (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-3 fusion
      protein, M-CSF, G-CSF, and erythropoietin, Thy-1+ cells showed a much higher
      numerical expansion of CD34+ cells (30,000-fold) and colony-forming cells (4,700
      fold) than was observed in cultures initiated with Thy-1- cells (900-fold
      increase in CD34+ cell numbers and 241-fold increase in CFC numbers). Cells
      coexpressing CD34 and Thy-1 were only transiently expanded (up to 29-fold) and
      were not detected after day 22 of culture. When CD34+ CD45RAlo CD71lo Thy-1+
      cells were cultured, either in semi-solid or liquid cultures, in the presence of
      anti-Thy-1 antibody, a significant reduction in progenitor cell numbers
      (particularly HPP-CFC) was observed. In contrast, CD34+ CD45RAlo CD71lo Thy-1-
      cells were not affected by anti-Thy-1. The results of this study indicate that
      Thy-1 is expressed on primitive cord blood progenitors with the highest in vitro
      proliferative potential, and further suggest that Thy-1 is involved in
      hematopoietic cell development, possibly by mediating a negative signal that
      results in inhibition of primitive cell proliferation.

PMID- 7513195
TI  - Abnormal antigen receptor-initiated signal transduction in lpr T lymphocytes.
AB  - The CD4-, CD8- double-negative (DN) T cells that accumulate in an age-dependent
      manner in peripheral lymphoid organs of lpr-homozygous mice display deficient
      activation in response to signals initiated by the antigen-specific T cell
      receptor (TCR)/CD3 complex. Abnormalities which could contribute to this defect
      include low expression and rapid TCR/CD3 modulation, loss of CD4, CD8, CD2 and Ly
      6.2, aberrant expression of CD45, and constitutive elevations of inositol
      phospholipid turnover, tyrosine phosphorylation, and expression of the p59fyn
      protein tyrosine kinase (PTK) and a few other protooncogenes. These properties
      strongly suggest that DN lpr T cells are chronically activated in vivo, perhaps
      by some self antigen(s), rendering them refractory to additional in vitro
      stimulation. Deficient activation of these cells is, therefore, most likely a
      secondary consequence of the Fas defect whose primary effect is allowing these
      aberrant cells to escape from the thymus and expand in the periphery.

PMID- 7513198
TI  - P-glycoprotein expression and function in circulating blood cells from normal
      volunteers.
AB  - In contrast to its clearly defined role as a multidrug efflux pump in neoplastic
      cells, the physiologic function of P-glycoprotein (P-gly) in normal cells is
      unclear. Recent reports identifying P-gly in normal blood and bone marrow suggest
      that hematopoietic development or function may be dependent on P-gly. To
      understand the normal function of P-gly in the blood, its level of expression and
      function must first be quantitated relative to a known standard. In this study, P
      gly, MDR1 gene expression, and P-gly function were quantitated in normal
      leukocytes. P-gly and MDR1 expression were analyzed in individual leukocyte
      lineages (T-helper, T-suppressor, monocyte, granulocyte, B-lymphocyte, NK cell)
      from normal volunteers. P-gly on the cell surface was detected by fluorescent
      double-labeling for lineage (CD4, CD8, CD14, CD15, CD19, CD56, respectively) and
      P-gly (MRK16) with analysis by flow cytometry and in some cases immunoblot
      analysis. MDR1 mRNA analysis on purified lineages was performed using
      quantitative reverse transcription-polymerase chain reaction. P-gly function was
      determined for each lineage using dual-labeling for lineage and P-gly substrate
      (rhodamine 123). The P-gly expressing human myeloma cell line, 8226/Dox6, was
      used as a reference of comparison for levels of P-gly, MDR1 mRNA, and function.
      CD56+ cells expressed the highest levels of MDR1 mRNA followed by CD8+ > CD4+
      approximately equal to CD15+ > CD19+ > CD14+, with percentage values relative to
      Dox6 of 49%, 17%, 8%, 8%, 4%, and 2%, respectively. The assays for P-gly
      immunofluorescence and function correlated well with mRNA analysis except for
      CD15+ cells (granulocytes), which showed a moderate MDR1 mRNA level with a lack
      of both function and surface P-gly staining. Granulocyte membranes did show P-gly
      on immunoblot analysis when probed with either C219 or JSB1. We conclude that (1)
      P-gly and the MDR1 mRNA are expressed in normal leukocytes, (2) this P-gly
      expression is lineage specific with relatively high levels among CD56+ cells, and
      (3) the expression of P-gly in granulocytes is not associated with transport of
      the P-gly substrate, rhodamine 123, out of the cell.

PMID- 7513199
TI  - Requirement for nuclear factor (NF)-kappa B p65 and NF-interleukin-6 binding
      elements in the tumor necrosis factor response region of the granulocyte colony
      stimulating factor promoter.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor
      produced by mesenchymal and myeloid cells following activation by inflammatory
      stimuli. It has previously been shown that a region of the G-CSF promoter, (-200
      to -165) containing the decanucleotide CK-1 element and two repeated sequences
      that resemble nuclear factor (NF)-interleukin-6 (IL-6) binding sites, is required
      for activation of the G-CSF gene by tumor necrosis factor-alpha (TNF-alpha) and
      IL-1 beta. We now show that the NF-kappa B p65 protein can bind to and activate
      this TNF response region. There are several unusual features of this p65
      interaction with the TNF response region. First, NF-kappa B p65 but not the
      related NF-kappa B p50 binds to the CK-1 element and a p50/65 hybrid protein that
      relies on the p50 rel homology domain for DNA binding does not transactivate the
      TNF response region. Second, p65 transactivation of this region is cell specific
      and requires not only its own binding site but also the NF-IL6 consensus sites.
      NF-IL6 also binds to the TNF response region of the G-CSF promoter.
      Electrophoretic mobility shift studies show that p65 and NF-IL6 can bind
      cooperatively to the TNF response region. The ability of this region to respond
      to TNF-alpha or p65 is correlated with the ability to form the p65/NF-IL6 ternary
      complex.

PMID- 7513200
TI  - Immature human cord blood progenitors engraft and proliferate to high levels in
      severe combined immunodeficient mice.
AB  - Unseparated or Ficoll-Hypaque (Pharmacia, Piscataway, NJ)--fractionated human
      cord blood cells were transplanted into sublethally irradiated severe combined
      immunodeficient (SCID) mice. High levels of multilineage engraftment, including
      myeloid and lymphoid lineages, were obtained with 80% of the donor samples as
      assessed by DNA analysis, fluorescence-activated cell sorting (FACS), and
      morphology. In contrast to previous and concurrent studies with adult human bone
      marrow (BM), treatment with human cytokines was not required to establish high
      level human cell engraftment, suggesting that neonatal cells either respond
      differently to the murine microenvironment or they provide their own cytokines in
      a paracrine fashion. Committed and multipotential myelo-erythroid progenitors
      were detected using in vitro colony assays and FACS analysis of the murine BM
      showed the presence of immature CD34+ cells. In addition, human hematopoiesis was
      maintained for at least 14 weeks providing further evidence that immature
      hematopoietic precursors had engrafted the murine BM. This in vivo model for
      human cord blood-derived hematopoiesis will be useful to gain new insights into
      the biology of neonatal hematopoietic cells and to evaluate their role in gene
      therapy. There is growing evidence that there are ontogeny-related changes in
      immature human hematopoietic cells, and therefore, the animal models we have
      developed for adult and neonatal human hematopoiesis provide useful tools to
      evaluate these changes in vivo.

PMID- 7513201
TI  - Role of P-selectin and leukocyte activation in polymorphonuclear cell adhesion to
      surface adherent activated platelets under physiologic shear conditions (an
      injury vessel wall model).
AB  - Carbohydrate moieties on leukocytes adhere to activated platelets via P-selectin
      under static binding condition studies. We characterize polymorphonuclear cell
      (PMN) surface interactions with surface adherent platelets and the PMNs response,
      under physiologic flow conditions corresponding to a shear of 100 s-1, in an in
      vitro flow chamber. Fluorescent labeled PMNs with red blood cells were drawn
      through a transparent flow channel and visually quantitated over 30 minutes,
      interacting with a confluent monolayer of activated, shear-spread platelets
      expressing P-selectin. PMN adhesion was saturable (2,250 +/- 350/mm2), and time
      and cation (Ca2+, Mg2+) dependent, and PMNs did not bind to the experimental
      surface in the absence of a platelet monolayer. P-selectin antibodies completely
      abolished PMN adhesion in a concentration-dependent manner with half inhibition
      at 70 micrograms/mL. Antibodies to a putative P-selectin receptor CD15 (80H5 and
      MMA) maximally inhibited PMN adhesion by 73% and 10%, respectively. Adherent PMNs
      appeared morphologically activated and flow cytometric analysis of adherent PMNs
      confirmed activation because CD11b and CD18 surface expression was upregulated
      (100% and 27%, respectively), whereas L-selectin was downregulated (55%) compared
      with control nonadherent PMNs. In the presence of the metabolic inhibitor sodium
      azide (0.02% and 0.1%) there was a 23% +/- 9% and 51% +/- 3% decrease,
      respectively, in PMN adhesion at 100 s-1. Thus, P-selectin is required for PMN
      adhesion to a pathophysiologic surface of activated adherent platelets at
      physiologic shear rates. Furthermore, a secondary step involving PMN activation
      after platelet binding appears necessary for complete (irreversible) adhesion to
      occur. This unique flow cell provides a model to explore, under controlled
      conditions, biologic mechanisms and ligands involved in leukocyte-platelet
      binding that play important roles in PMN localization at sites of thrombosis and
      vascular injury.

PMID- 7513202
TI  - Role of cyclic nucleotides in rapid platelet adhesion to collagen.
AB  - Adhesion of human platelets to type I collagen under arterial flow conditions is
      extremely fast, being mediated primarily by the alpha 2 beta 1 integrin
      (glycoprotein Ia/IIa). We have investigated the involvement of cyclic nucleotides
      in platelet adhesion to soluble native collagen immobilized on Sepharose beads
      using a new microadhesion assay under arterial flow conditions. To prevent
      platelet stimulation by thromboxanes and adenosine diphosphate (ADP), experiments
      were performed with aspirin-treated platelets in the presence of ADP-removing
      enzyme systems such as creatine phosphate/creatine phosphokinase or apyrase.
      Rapid reciprocal changes in platelet adenosine 3'5'-cyclic monophosphate (cAMP)
      and guanosine 3'5'-cyclic monophosphate (cGMP) occurred during adhesion. cAMP
      levels in adherent platelets were 2.4-fold lower than in effluent platelets or in
      static controls, whereas cGMP levels were increased 2.4-fold. These results
      suggest that contact between platelets and collagen stimulates guanylate cyclase
      and inhibits adenylate cyclase. This occurs in the absence of the platelet
      release reaction. We also studied short-term effects of agents that regulate
      cyclic nucleotide synthesis, prostaglandin E1 (PGE1) and sodium nitroprusside
      (SNP). After only 3.8 seconds at 10 to 30 dyne/cm2, PGE1 (10 mumol/L) increased
      cAMP 16.4-fold, whereas SNP (50 mumol/L) increased cGMP ninefold and caused a 3.2
      fold increase in cAMP. Both PGE1 and SNP rapidly (< 5 seconds) inhibited platelet
      adhesion in a dose-dependent manner that was correlated with the increase in
      cyclic nucleotides. Our data suggest that cAMP and cGMP play a regulatory role in
      the initial phases of platelet adhesion to collagen mediated by the alpha 2 beta
      1 integrin receptor.

PMID- 7513203
TI  - Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS
      binding protein and CD14, and inhibition by a recombinant fragment of
      bactericidal/permeability-increasing protein.
AB  - Mononuclear phagocytes, stimulated by bacterial lipopolysaccharide (LPS), have
      been implicated in the activation of coagulation in sepsis and endotoxemia. In
      monocytes LPS induces the synthesis of tissue factor (TF) which, assembled with
      factor VII, initiates the blood coagulation cascades. In this study we
      investigated the mechanism of LPS recognition by monocytes, and the consequent
      expression of TF mRNA and TF activity. We also studied the inhibition of these
      effects of LPS by rBPI23, a 23-kD recombinant fragment of
      bactericidal/permeability increasing protein, which has been shown to antagonize
      LPS in vitro and in vivo. Human peripheral blood mononuclear cells, or monocytes
      isolated by adherence, were stimulated with Escherichia coli O113 LPS at
      physiologically relevant concentrations (> or = 10 pg/mL). The effect of LPS was
      dependent on the presence of the serum protein LBP (lipopolysaccharide-binding
      protein), as shown by the potentiating effect of human recombinant LBP or serum.
      Furthermore, recognition of low amounts of LPS by monocytes was also dependent on
      CD14 receptors, because monoclonal antibodies against CD14 greatly reduced the
      LPS sensitivity of monocytes in the presence of serum or rLBP. Induction of TF
      activity and mRNA expression by LPS were inhibited by rBPI23. The expression of
      tumor necrosis factor showed qualitatively similar changes. Considering the
      involvement of LPS-induced TF in the potentially lethal intravascular coagulation
      in sepsis, inhibition of TF induction by rBPI23 may be of therapeutic benefit.

PMID- 7513204
TI  - Development of progressive kidney damage and myeloma kidney in interleukin-6
      transgenic mice.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine that has been postulated as
      playing a role in the pathogenesis of multiple myeloma, chronic autoimmune
      diseases, and alcoholic liver cirrhosis. We generated transgenic mice carrying a
      fusion between the mouse metallothionein-I (MT-I) gene promoter and the human IL
      6 cDNA. MT-I/IL-6 transgenics express IL-6 constitutively in the liver and
      secrete the cytokine in the blood. They show initially activation of acute-phase
      response genes and accumulation of alpha 2- and beta-globulins in the plasma,
      which is followed by polyclonal hypergammaglobulinemia. MT-I/IL-6 transgenics die
      between 12 to 20 weeks of age. Histologic examination of transgenic animals at
      different ages and after necropsy showed, as expected from previous studies of IL
      6 disregulation in vivo, an increase in the number of megakaryocytes in the
      spleen and bone marrow and, at later stages, IgG plasmacytosis in the spleen,
      lymph nodes, and thymus. However, no plasma cell infiltration was detected in
      other organs. The distinguishing feature of MT-I/IL-6 transgenics is the
      development of a progressive kidney pathology, in which the initial membranous
      glomerulonephritis is followed by focal glomerulosclerosis and finally by
      extensive tubular damage that reproduces the damage observed in patients at
      terminal stages of multiple myeloma (myeloma kidney). The pathogenetic role of IL
      6 overproduction and of the resulting serum protein overload in the kidney damage
      is discussed.

PMID- 7513205
TI  - T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a
      ligand for CD28.
AB  - The activation of T cells requires two distinct signals. One signal involves
      interaction of the antigen-specific T-cell receptor with major histocompatibility
      complex molecules plus antigenic peptide; a second signal, which is antigen
      nonspecific, is the interaction of CD28 with its natural ligands B7-1 and B7
      2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and
      binds to B7 gene-family members, found on antigen-presenting cells. Because of
      our interest in the immunologic basis of benign and malignant T-cell-mediated
      disorders of the skin, we investigated the cellular distribution of CD28 and B7
      family members in lesions of psoriasis and mycosis fungoides. By immunostaining
      cryostat sections of skin, CD28 was found to be expressed on virtually all
      lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7-1
      was also found to be expressed on virtually all lymphocytes in the epidermis and
      dermis of both skin diseases. B7-1 expression was confirmed on CD3+ T lymphocytes
      using flow cytometry of single cell suspensions of fresh, unfixed psoriatic
      lesional tissue. To exclude the possibility that this result was caused by a
      second reagent contaminating the monoclonal antibody (MoAb) preparation, two
      different lots were used, and the MoAb was absorbed onto Chinese hamster ovary
      (CHO) transfectants expressing B7-1, or vector-only transfected CHO cells. These
      procedures confirmed that a B7-1-like epitope was being recognized on psoriatic
      lesional T cells. In contrast to B7-1 expression on lymphocytes, B7-3, as defined
      by anti-BB-1 MoAb reactivity, was found primarily on epidermal keratinocytes in
      both skin diseases and was not found on T cells. These results indicate that
      within two common skin disorders, lesional T cells accumulate in the dermis and
      epidermis, which express B7-1. Such expression may permit self-costimulation
      involving the CD28-mediated activation pathway, and thereby contribute to the
      ongoing T-cell proliferation present in these chronic, benign, and malignant skin
      diseases.

PMID- 7513207
TI  - Surface phenotype and Ig heavy-chain gene usage in chronic B-cell leukemias:
      expression of myelomonocytic surface markers in CD5- chronic B-cell leukemia.
AB  - We investigated the surface expression of leukocyte differentiation antigens and
      the Ig heavy-chain variable region (VH) gene family use in leukemic cells from 26
      Japanese patients with chronic B-cell leukemias with special reference to CD5
      antigen expression. CD5 was expressed on leukemic cells in 21 of 26 cases (CD5+)
      but not in 5 cases (CD5-). Myelomonocytic marker, CD13 antigen was expressed on
      the leukemic cells in all 5 CD5- cases but in none of CD5+ cases. Leukemic cells
      in CD5- cases also expressed CD11b antigen more frequently than those in CD5+
      cases (80% v 11%; P < .01). Another myeloid marker, CD33, was expressed neither
      on CD5+ nor CD5- leukemic cells. CD22, a restricted B-cell marker, was expressed
      more frequently on CD5- leukemic cells than on CD5+ leukemic cells (80% v 33%; P
      < .05). Another restricted B-cell activation marker, CD23, was expressed at
      similar frequency in both the CD5+ and CD5- groups (67% v 60%). Although CD45RA
      was expressed on the majority of leukemic B cells, the CD45RA expression level
      was significantly higher among CD5- cases than CD5+ cases (P < .01). In the
      analysis of VH gene expressed in chronic B-cell leukemias by polymerase chain
      reaction amplification, CD5+ cases preferentially used VH4 family members (48%;
      10 of 21). CD5- cases, on the other hand, mainly used VH3 family (80%; 4 of 5).
      Thus, from our present observation of an albeit limited patient population, we
      have found an association between VH gene family use and CD5 antigen expression
      in chronic B-cell leukemias. We have also shown the differential expression of
      myelomonocytic markers in the CD5+ and CD5- chronic B-cell leukemias. These
      result are in agreement with previous suggestions that CD5 positivity is the
      hallmark for distinct clinical entity commonly referred to in the literature as
      chronic lymphocytic leukemia.

PMID- 7513206
TI  - Differentiation of natural killer (NK) cells from human primitive marrow
      progenitors in a stroma-based long-term culture system: identification of a
      CD34+7+ NK progenitor.
AB  - We have recently described a marrow stroma-dependent long-term culture system
      that supports differentiation of CD34+ human marrow primitive progenitors into
      natural killer (NK) cells. We postulate that CD7 expression may be an early event
      in commitment of hematopoietic progenitors to the NK lineage. Here we compare the
      characteristics of CD34+7- and CD34+7+ marrow cells cultivated in the stroma
      based NK culture system. These CD34+ populations were further compared with a
      marrow derived, more committed, CD34-7+ progenitor to emphasize the continuum of
      NK development and to highlight differences between progenitors in our assays. No
      progenitor proliferated when plated in media without stroma, underscoring the
      importance of stroma in NK differentiation. Plating progenitor populations in
      interleukin-2 containing media directly on preestablished, allogeneic, irradiated
      marrow stroma for 5 weeks resulted in CD56+CD3- NK cells; however,
      characteristics of the cultured populations differed. Fold expansion and cloning
      efficiency of the CD34+7+ population, determined by a functional limiting
      dilution assay was significantly higher than of the CD34+7- or CD34+7+
      populations. This suggests that the CD34+7+ population is highly enriched for an
      NK progenitor and a possible intermediate in NK lineage differentiation. Further
      dividing the CD34+7+ population by the relative fluorescence of CD7 into
      CD34+7+dim and CD34+7+bright populations showed that the CD34+7+bright population
      exhibited a significantly higher cloning frequency than parallel experiments with
      CD34+7+dim cells (11.8% +/- 2.4% v 2.4% +/- 0.7%, n = 6; P = .005). Plating of
      the more primitive CD34+7- population in a transwell system (which separates
      progenitors from stroma by a microporous membrane) prevents differentiation into
      NK cells. In contrast, plating of CD34+7+ progenitors in transwells resulted in
      generation of NK cells. These data suggest that primitive, but not more mature NK
      progenitors may require direct contact with stroma for the initial
      differentiation steps. Finally, differentiation of the NK progenitors in this
      stroma-dependent model results in expression of CD2 not present on any of the
      starting populations. This observation suggests that marrow stroma can stimulate
      CD2 expression on NK progenitors in a previously undescribed fashion that may be
      analogous to the thymic effect on CD2 expression in immature T lymphocytes. These
      observations identify early steps in the commitment of primitive marrow CD34+
      hematopoietic progenitors to a lymphoid lineage and underscore the importance of
      coexpression of CD7 with CD34 as an early lymphoid commitment characteristic and
      direct progenitor-stroma interactions in this process.

PMID- 7513208
TI  - Ligand-independent activation of c-kit receptor tyrosine kinase in a murine
      mastocytoma cell line P-815 generated by a point mutation.
AB  - The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play
      a crucial role in hematopoiesis, especially in mast cell growth and
      differentiation. Although a number of dominant loss-of-function mutations of c
      kit gene have been well characterized in mice, rats, and humans, little is known
      about the c-kit mutations contributing to ligand-independent activation of the c
      kit receptor tyrosine kinase (KIT). In a murine mastocytoma cell line, P-815, KIT
      has been found to be constitutively phosphorylated on tyrosine and activated in a
      ligand-independent manner. Sequencing of the whole coding region of c-kit cDNA
      showed that c-kit cDNA of P-815 cells carries a point mutation in codon 814,
      resulting in amino acid substitution of Tyr for Asp. Murine wild-type c-kit cDNA
      and mutant-type c-kit cDNA encoding Tyr in codon 814 were expressed in cells of a
      human embryonic kidney cell line, 293T. In the transfected cells, mutant-form
      KITTyr814 was strikingly phosphorylated on tyrosine and activated in immune
      complex kinase reaction regardless of stimulation with a ligand for KIT (stem
      cell factor), whereas tyrosine phosphorylation and activation was barely
      detectable in wild-form KIT. The data presented here provide evidence for a novel
      activating mutation of c-kit gene that might be involved in neoplastic growth or
      oncogenesis of some cell types, including mast cells.

PMID- 7513209
TI  - Self-renewal and differentiation of stem cells in a biopotential murine leukemia:
      an in vitro model for differentiation therapy.
AB  - PGM-2 is a variant of the transplantable PGM-1 leukemia of strain C3H/HeJ.
      Freshly explanted cells had lymphoid morphology with a CD5+ CD45R (B220)- IgM-
      phenotype. They were not viable in unstimulated cultures, but formed IgM+
      lymphoid colonies in response to interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-7,
      and Steel factor, and macrophage colonies in response to IL-3. IL-3-stimulated
      colonies had no recloning potential, but colonies from IL-7 cultures gave rise to
      large numbers of secondary macrophage colonies in IL-3-stimulated cultures and
      secondary lymphoid colonies in IL-7-stimulated cultures. The latter ones could be
      serially transferred in vitro for several months, and formed typical PGM-2 tumors
      in vivo. IL-7-stimulated colonies could therefore be used to measure leukemic
      stem cells in vitro. Supramaximal IL-3 stimulation (2,500 U/mL) of suspension
      cultures was followed by an increase in overall cell numbers and a disappearance
      of leukemic stem cells, compatible with differentiation induction. This could not
      be counteracted by simultaneous stimulation with IL-7. However, lower IL-3
      concentrations (500 U/mL) induced an expansion of the stem cell pool, possibly by
      facilitating density-dependent autostimulatory mechanisms involving endogenous
      production of IL-7. The system described is a simple in vitro model for
      differentiation therapy. It shows that leukemic stem cells can be induced by
      hematopoietic growth factors to undergo terminal differentiation, but the
      concentrations required for differentiation induction in stem cells are much
      higher than those required for other biologic effects. Submaximal stimulation may
      favor expansion rather than repression of the leukemic cell population.

PMID- 7513210
TI  - Reactive oxygen species rapidly increase endothelial ICAM-1 ability to bind
      neutrophils without detectable upregulation.
AB  - We compared the effects of phorbol 12-myristate 13-acetate (PMA) and thrombin
      with those of nonlytic concentrations of reactive oxygen species (ROS) generated
      by hypoxanthine (HX)-xanthine oxidase (XO) on the adhesion properties of human
      umbilical cord vein endothelial cells (HUVEC) to resting polymorphonuclear
      neutrophils (PMN). PMN adherence to HX-XO-treated HUVEC was increased
      approximately twofold to 2.5-fold relative to untreated HUVEC, both immediately
      and after 2 hours. It was not additive to that induced by PMA or thrombin
      stimulation of HUVEC. ROS-induced adherence was not due to platelet-activating
      factor (PAF) or P-selectin expression, as it was neither antagonized by BN52021
      (PAF receptor antagonist) nor inhibited by anti-P-selectin monoclonal antibody
      (MoAb), contrary to the increased adhesion of PMA- and thrombin-stimulated HUVEC.
      PMN preincubated with mannose-6-P or N-acetylneuraminic acid (sialic acid), but
      not mannose or galactose-6-P, showed reduced adherence to ROS-treated HUVEC,
      suggesting that carbohydrate molecules were expressed on the latter and served as
      the ligand for the PMN L-selectin. Intercellular adhesion molecule (ICAM-1),
      constitutively present on the surface of resting HUVEC, was involved in the PMN
      adherence to ROS-treated HUVEC, since this adherence was inhibited by anti-ICAM
      1, anti-CD11a, anti-CD11b, and anti-CD18 MoAbs. A non-CD18, non-ICAM-1-dependent
      mechanism is also involved in this adherence, since effects of these MoAbs were
      not additive; moreover, combinations of anti-CD18 and anti-ICAM-1 MoAbs with
      mannose-6-P and sialic acid completely inhibited PMN adherence. The increased
      binding of PMN to HX-XO-exposed HUVEC observed here involved IC-AM-1, but was
      independent of its upregulation, and another non-ICAM-1-dependent mechanism, in
      which carbohydrates expressed on HUVEC recognize L-selectin on PMN.

PMID- 7513211
TI  - Deformation of swollen erythrocytes provides a model of sickling-induced leak
      pathways, including a novel bromide-sensitive component.
AB  - Deoxygenation-induced red blood cell (RBC) sickling probably activates multiple
      cation leak pathways. In an attempt to model this, we examined the net passive K
      efflux ("K leak") from normal and sickle RBCs undergoing elliptical deformation
      in hypotonic media (200 mOsmol/L). This hypotonic deformation activates two
      deformation-dependent K leak pathways that are not detectable during the balanced
      leak (Kefflux = Nainflux) resulting from deformation of RBCs in isotonic medium.
      These are (1) a calcium-dependent leak component and (2) a novel leak pathway
      that is inhibited by substitution of bromide (but not sulfamate) for chloride,
      which converts the unbalanced K leak (Kefflux > Nainflux) of hypotonic
      deformation to a residual balanced leak. This dramatic effect of hypotonic
      deformation is reversible, is detected in both normal and sickle RBCs, and is
      inhibited significantly by 4,4'-diisothiocyano-2,2'-stilbene disulfonate.
      Remarkably, bromide also inhibits by 55% the K leak resulting from authentic
      deoxygenation-induced RBC sickling and, thereby, blunts the imbalance of
      accompanying monovalent cation leaks. The unique effect of bromide is not readily
      explainable on the basis of known behaviors of known ion leak/transport pathways.
      The mechanical threshold for triggering K leak during hypotonic deformation is at
      applied shear stress of 164 dyne/cm2, a value similar to the abnormal
      susceptibility we previously found for oxygenated sickle RBCs during isotonic
      deformation. These data suggest that membrane stretch accompanying hypotonic
      deformation activates the same multiple leak pathways that contribute to net K
      leak during authentic RBC sickling, including a previously unknown bromide
      sensitive leak.

PMID- 7513213
TI  - Low expression of E-selectin in diseased tissues from human immunodeficiency
      virus-positive patients.

PMID- 7513212
TI  - Effect of cell concentration on bone marrow and peripheral blood stem cell
      cryopreservation.
AB  - The effects of cell concentration during cryopreservation on bone marrow (BM) or
      peripheral blood (PB)-derived hematopoietic progenitor cells have not been
      described. The much greater numbers of cells harvested for autologous PB stem
      cell (PBSC) transplantation requires that the cells be frozen at higher cell
      concentrations, or in much greater volumes, compared with BM. We cryopreserved
      108 PBSC collections from 30 patients at an average (+/- SD) cell concentration
      of 3.7 +/- 1.9 x 10(8) nucleated cells per mL in 127 +/- 45 mL. The proportion of
      mononuclear cells was 52.9% +/- 27.2%. The products also contained 2.9 +/- 2.1 x
      10(9) platelets/mL and an average red cell proportion of 12.9% +/- 7.2%. The
      nucleated cell recovery after thawing was 75.4% +/- 13.0%. The nucleated cell
      concentration during freezing was not predictive for the postthaw recoveries of
      nucleated cells (P = .38), granulocyte-macrophage colony-forming unit (P = .06)
      or CD34+ cells (P = .54), or for the viability of mononuclear cells (P = .81).
      The platelet and red cell concentrations similarly were not predictive for these
      endpoints. Samples (3 BM, 7 PBSC) from 10 patients were simultaneously
      cryopreserved at two-fold, and from 5 additional patients (PBSC) at 6- to 24-fold
      differing cell concentrations. A lower recovery of erythroid burst forming unit
      was found for samples frozen at higher cell concentrations (P = .04), but no
      significant differences were found in the other endpoints listed above. The
      average cell concentration during freezing for each patient's PBSC collections (n
      = 34 patients) did not predict time to achieve a PB count of > 500
      granulocytes/microL (P = .51) or platelet transfusion independence (P = .39).
      Patients achieved these endpoints of engraftment at medians of 12 and 13 days,
      respectively. The infusion of these products was generally well tolerated.
      Similarly, the cell concentration at which BM cells were frozen did not predict
      for the duration of granulocyte (P = .63) or platelet (P = .36) aplasias for 54
      patients undergoing autologous BM transplantation. These data suggest that PBSC
      or BM cells collected for transplantation may be cryopreserved at very high cell
      concentrations without loss of engraftment potential or undue infusion-related
      toxicity.

PMID- 7513214
TI  - Matrix-assisted laser desorption/ionization with an external ion source Fourier
      transform mass spectrometer.
AB  - Mass spectra of several model oligopeptides (substance P, [Arg8]-vasopressin,
      tyrothricin, and the B-chain of bovine insulin) have been obtained with a matrix
      assisted laser desorption/ionization (MALDI) source and a custom-designed Fourier
      transform mass spectrometer (FTMS). The MALDI source is outside the magnetic
      field in a separately pumped external chamber, and ions are injected through the
      fringing fields of the magnet and into the FTMS analyzer cell by a long
      quadrupole mass filter that is operated in the RF-only mode. A large window on
      the ion source housing makes it easy to point and focus the laser beam onto the
      sample probe tip. A good quality mass spectrum is achieved for 0.5 pmol of
      substance P, and the mass resolution for the B-chain of bovine insulin is 19,000.

PMID- 7513217
TI  - Inhibition of Semliki Forest virus multiplication in L-cells by combinations of
      interferon and ribavirin as measured by plaque titration and direct enzyme
      immunoassay.
AB  - Inhibition of Semliki Forest virus (SFV) multiplication in L-cell monolayers by
      combinations of mouse interferon (IFN) and ribavirin was measured by plaque
      titration and by direct enzyme immunoassay of SFV in L-cells. When critically
      inhibitory quantities of IFN and ribavirin were combined, an additive inhibitory
      effect was observed in either assay.

PMID- 7513215
TI  - A nuclear factor required for specific translation of cyclin B may control the
      timing of first meiotic cleavage in starfish oocytes.
AB  - In most animals, the rate of cyclin B synthesis increases after nuclear envelope
      breakdown during the first meiotic cell cycle. We have found that cyclin B-cdc2
      kinase activity drops earlier in emetine-treated than in control starfish
      oocytes, although the protein synthesis inhibitor does not activate the cyclin
      degradation pathway prematurely. Moreover, protein synthesis is required to
      prevent meiotic cleavage to occur prematurely, sometimes before chromosomes have
      segregated on the metaphase plate. In normal conditions, increased synthesis of
      cyclin B after germinal vesicle breakdown (GVBD) balances cyclin degradation and
      increases the time required for cyclin B-cdc2 kinase to drop below the level that
      inhibits cleavage. Taken together, these results point to cyclin B as a possible
      candidate that could explain the need for increased protein synthesis during
      meiosis I. Although direct experimental evidence was not provided in the present
      work, cyclin B synthesis after GVBD may be important for correct segregation of
      homologous chromosomes at the end of first meiotic metaphase, as shown by a
      variety of cytological disorders that accompany premature cleavage. Although the
      overall stimulation of protein synthesis because of cdc2 kinase activation is
      still observed in oocytes from which the germinal vesicle has been removed before
      hormonal stimulation, the main increase of cyclin B synthesis normally observed
      after germinal vesicle breakdown is suppressed. The nuclear factor required for
      specific translation of cyclin B after GVBD is not cyclin B mRNA, as shown by
      using a highly sensitive reverse transcription followed by polymerase chain
      reaction procedure that failed to detect any cyclin B mRNA in isolated germinal
      vesicles.

PMID- 7513218
TI  - Promising new developments in the systemic treatment of ovarian cancer.
AB  - Advanced-stage cancer of the ovary is the most lethal of gynecologic
      malignancies, affecting African-American and white women with approximately equal
      frequency. In large part, ovarian cancer's lethality is due to the fact that most
      women are diagnosed with disease that is widespread throughout the abdomen and
      pelvis. This article reviews recent developments in the identification of new
      treatment approaches to ovarian cancer. Discussion focuses on current drug
      development activities of the Medical Ovarian Cancer Section of the National
      Cancer Institute, with reference to pertinent literature from other institutions.
      The drugs discussed are in clinical trials as of this writing. They include
      paclitaxel, an agent with a novel molecular mechanism of action; colony
      stimulating factors, which enhance the therapeutic index of cytotoxic agents; and
      the antiproliferative agents suramin and carboxyamidotriazole.

PMID- 7513219
TI  - Infection with hepatitis C virus. Intravenous gammaglobulin may still infect
      patients.

PMID- 7513216
TI  - Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks
      initiation of M-phase.
AB  - The cdc25 phosphatase is a mitotic inducer that activates p34cdc2 at the G2/M
      transition by dephosphorylation of Tyr15 in p34cdc2. cdc25 itself is also
      regulated through periodic changes in its phosphorylation state. To elucidate the
      mechanism for induction of mitosis, phosphorylation of cdc25 has been
      investigated using recombinant proteins. cdc25 is phosphorylated by both cyclin
      A/p34cdc2 and cyclin B/p34cdc2 at similar sets of multiple sites in vitro. This
      phosphorylation retards its electrophoretical mobility and activates its ability
      to increase cyclin B/p34cdc2 kinase activity three- to fourfold in vitro, as
      found for endogenous Xenopus cdc25 in M-phase extracts. The threonine and serine
      residues followed by proline that are conserved between Xenopus and human cdc25
      have been mutated. Both the triple mutation of Thr48, Thr67, and Thr138 and the
      quintuple mutation of these three threonine residues plus Ser205 and Ser285,
      almost completely abolish the shift in electrophoretic mobility of cdc25 after
      incubation with M-phase extracts or phosphorylation by p34cdc2. These mutations
      inhibit the activation of cdc25 by phosphorylation with p34cdc2 by 70 and 90%,
      respectively. At physiological concentrations these mutants cannot activate
      cyclin B/p34cdc2 in cdc25-immunodepleted oocyte extracts, suggesting that a
      positive feed-back loop between cdc2 and cdc25 is necessary for the full
      activation of cyclin B/p34cdc2 that induces abrupt entry into mitosis in vivo.

PMID- 7513220
TI  - Tumor necrosis factor and human acute leukemia.
AB  - Tumor necrosis factor (TNF) is a major regulator of AML growth in vitro and
      markedly enhances AML growth induced by GM-CSF/IL-3. TNF, on the other hand,
      suppresses the G-CSF stimulated AML cell proliferation and serves as a modulator
      of growth factor receptors on AML cells. It upregulates GM-CSF and IL-3 receptors
      by a mechanism which depends on new protein synthesis and downregulates G-CSF
      receptors by activation of protein kinase C (PCK). The leukemic cells from
      patients with acute or chronic leukemias have similar TNF receptor structures (MW
      76 kD). Serum TNF levels increase in patients with both acute and chronic
      leukemias especially in those with advanced disease. The clinical application of
      TNF in association with GM-CSF or IL-3 may be of value for patients with AML.

PMID- 7513222
TI  - Perception of surgical pain by nurses and patients.
AB  - A descriptive study of postoperative patients was conducted to determine if there
      were any differences in the pain ratings of nurses and patients using a 10
      centimeter graphic rating scale (GRS). The sample consisted of 16 patients: 3
      males and 13 females. There were 13 nurses: 54% R.N.s and 46% L.P.N.s. When
      patients requested pain medication, both the patient and nurse were asked
      independently to indicate their perception of the patient's pain on the scale.
      The mean patient score on the GRS was 7.59; the mean for nurses was 4.59. At test
      revealed a significant difference between the nurses' and patients' pain ratings
      (t = 4.22, p = .0002). Based on this study, there is further need to examine
      assessment of the patient and the perceptions of the nurse and patient.

PMID- 7513221
TI  - Lymphoma-associated pancreatitis as a presenting manifestation of immunoblastic
      lymphoma.
AB  - A 55 year old man presented with clinical signs and symptoms of subacute
      pancreatitis of unknown aetiology. Two weeks later, inguinal lymphadenopathy
      developed and a lymph node biopsy revealed a B cell immunoblastic lymphoma.
      Computerized tomography showed enlargement of the pancreas and imaging features
      consistent with pancreatitis. Administration of VACOP-B combination chemotherapy
      achieved complete resolution of the pancreatic mass and the enlarged lymph nodes.
      We consider this patient to have had lymphoma associated pancreatitis. This case
      represents a rare clinical presentation of lymphoma suggesting an alternative
      aetiology of subacute pancreatitis in some cases.

PMID- 7513223
TI  - [The effect of the posttetanic potentiation of slices of rat cerebral cortex on
      the protein and RNA content in the neurons and gliocytes].

PMID- 7513224
TI  - Local etoposide injection for treatment of tubal pregnancy with cardiac activity.
AB  - Etoposide was injected locally under sonographic management for the treatment of
      tubal pregnancy with cardiac activity in the distal region of the tube; the serum
      beta-hCG level was 14,000 mIU/mL. Two doses of 50 mg each, three days apart, were
      employed. No side effects appeared either during or after the treatment.
      Hysterosalpingography performed 1 month 3 weeks after treatment demonstrated the
      patency of the affected tube. Local etoposide instillation may be an option in
      the management of unruptured ectopic pregnancies, even in the presence of fetal
      cardiac activity and high trophoblastic activity.

PMID- 7513225
TI  - Variants of Nijmegen breakage syndrome and ataxia telangiectasia.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by
      telangiectasia, progressive ataxia, sinopulmonary infections and a combined
      immunodeficiency (usually consisting of IgA deficiency, IgE deficiency, IgG2 and
      IgG4 deficiency and a disturbed T cell immunity). The alpha-fetoprotein level is
      elevated. Cytogenetic studies reveal a very specific chromosome instability with
      multiple chromosome 7 and/or 14 rearrangements (preferential breakpoints 14q32,
      14q12, 7q35 and 7p12). X-ray hypersensitivity is one of the hallmarks of the
      disease. Nijmegen Breakage Syndrome (NBS), an autosomal recessive disorder with
      some features of AT, was first reported in 1981. At this moment at least 19
      patients have been recognized. Clinical symptoms are microcephaly from birth, a
      peculiar face, growth retardation, repeated respiratory tract infections and
      renal abnormalities. Immunological, cytogenetic and cell-biological findings in
      NBS are identical to AT. However, alpha-fetoprotein levels are not increased. A
      tendency toward malignancy has been demonstrated in both syndromes. Recently, we
      encountered three patients with variants of these syndromes.

PMID- 7513227
TI  - Safety of rapid subcutaneous gammaglobulin infusions in patients with primary
      antibody deficiency.

PMID- 7513226
TI  - Leukocyte adhesion deficiency (LAD) II: a new adhesion defect due to absence of
      sialyl Lewis X, the ligand for selectins.

PMID- 7513228
TI  - Dimensions of procedural pain and its analgesic management in critically ill
      surgical patients.
AB  - BACKGROUND AND PURPOSE: Many critically ill patients undergo endotracheal
      suctioning and chest tube removal procedures, yet little documentation of
      associated pain exists. Therefore, a study was conducted to (1) compare the
      magnitude and dimensions of pain associated with endotracheal suctioning and
      chest tube removal in intubated and nonintubated patients and (2) correlate
      preprocedural analgesic administration and pain magnitude. METHODS: Multiple
      dimensions of pain (ie, intensity, extent, sensation, and affect) were measured
      after postoperative cardiovascular surgery patients underwent endotracheal
      suctioning (N = 45) or chest tube removal (N = 35). Preprocedural analgesics and
      intubation status during pain assessments were noted. RESULTS: Patients reported
      lower pain intensity with endotracheal suctioning (mean, 4.9 on a 0-10 numerical
      rating scale) than with chest tube removal (mean, 6.6). Pain extent, sensation,
      and affect scores were relatively low for endotracheal suctioning and chest tube
      removal. Similar words such as "tender," "sharp," and "heavy" were used to
      describe both procedures; however, more patients described their response to
      chest tube removal as "fearful." Intubated patients had different pain
      experiences than extubated patients. Patients received little analgesic
      premedication, and correlations were low and nonsignificant between amount of
      medication received and pain magnitude. CONCLUSIONS: Patients were able to
      communicate extensive information about procedural pain, even when intubated.
      Endotracheal suctioning and chest tube removal were both painful; yet, there was
      little preparatory analgesic management of the pain. Research is needed to
      investigate a variety of pharmacological and nonpharmacological interventions for
      pain related to endotracheal suctioning and chest tube removal.

PMID- 7513229
TI  - A survey of pain assessment and management practices among critical care nurses.
AB  - BACKGROUND: Postoperative pain is one of the major obstacles in the prevention of
      complications during patient recovery. Pain and its management have gained great
      interest among researchers, clinicians and policy-makers. PURPOSES: To explore
      the relationship between two variables in pain assessment (length of time after
      surgery and ventilator status) and medication decisions made by critical care
      nurses, and to identify nurses' concerns about opioid use. METHODS: A convenience
      sample of 71 critical care nurses participated in the survey. RESULTS: Certain
      patient conditions such as length of time after surgery and ventilator status
      affected nurses' assessment and management of pain. Nurses' knowledge about pain
      assessment and management may affect patient care and outcomes.

PMID- 7513231
TI  - Gonorrhoea in the West Midlands.
AB  - The number of cases of gonorrhoea in residents of areas served by district health
      authorities of the West Midlands has been measured to provide an indicator of
      this population's sexual health. A detailed data set was collected on all cases
      of gonorrhoea diagnosed at genitourinary medicine (GUM) clinics in the West
      Midlands region during a three month period. Consultants in genitourinary
      medicine and colleagues in public health medicine cooperated, and data collection
      was complete for all but one clinic. The numbers of new cases of gonorrhea seen
      at GUM clinics varied widely between districts. The number of cases in the first
      quarter of 1992 in several districts implied a much higher incidence than the
      national annual rate of 61 new cases per 100,000 population in 1990. The routine
      workload statistics (KC60) from GUM clinics do not provide data on cases' area of
      residence. Further special surveys are needed to monitor trends in particular
      populations to assist progress towards targets for sexual health.

PMID- 7513232
TI  - Possible association of influenza A with fetal loss: investigation of a cluster
      of spontaneous abortions and stillbirths.
AB  - It has been suspected that influenza infection is associated with fetal or
      perinatal mortality, but little recent evidence supports this hypothesis. A small
      cluster of early and late fetal deaths in early 1986 prompted an epidemiological
      investigation. Women whose pregnancies were affected (cases) were compared with
      women whose pregnancies had a normal outcome (controls). Case pregnancies were
      distinguished by a significant excess of recent flu-like illness (p = 0.006), and
      were significantly more likely than controls to have serological evidence of
      influenza A infection (p = 0.00067), predominantly the influenza A H3N2,
      Christchurch/4/85-like strain. The cluster was recognised because most cases were
      patients of one health centre. Larger epidemiological studies will be needed to
      confirm an association between influenza A and fetal death, but this cluster
      suggests that influenza A may have an adverse influence on fetal survival.

PMID- 7513234
TI  - European surveillance of Legionnaires' disease associated with travel.

PMID- 7513233
TI  - Zoonotic transmission of giardiasis: a case control study.
AB  - A case control study of locally acquired giardiasis was carried out in a district
      in East Anglia. Thirty-three primary cases were matched for age and sex with 112
      controls selected from Family Health Service Authority registers. An association
      was shown between giardiasis and contact with farm animals (odds ratio 4.77;
      confidence interval 1.31-17.38) and pets (odds ratio 14.55; confidence interval
      4.18-50.62).

PMID- 7513230
TI  - Noninvasive positive pressure ventilation for patients with terminal respiratory
      failure: the ethical and economical costs of dealing with the inevitable are too
      great.

PMID- 7513237
TI  - Vancomycin resistance in enterococci.

PMID- 7513236
TI  - Hepatitis C virus associated with Irish anti-D immunoglobulin.

PMID- 7513235
TI  - Joint statements on preventing tuberculosis.

PMID- 7513238
TI  - Stroke mortality trends. An international perspective.
AB  - This article presents death rates for cerebrovascular disease (stroke) by sex for
      ages 35 to 74 years in 1990 for 52 countries, and trends in rates from 1950 to
      1990 for 30 countries. Rates are high in Asia and eastern Europe. In most
      industrialized countries, large declines occurred, particularly over the last 2
      decades. The United States and Canada have low rates. Portugal, Trinidad,
      Paraguay, Mauritius, China, Korea, and most eastern European countries have the
      highest rates. Japan, with very high stroke mortality in the 1950s, experienced
      the largest absolute and percent decline and now ranks above western Europe and
      North America but below most other countries. In most industrialized countries,
      except in eastern Europe, stroke death rates declined more than 50% since 1970,
      somewhat more in women than in men. There is more uniformity in trends since 1970
      than in earlier years. In several countries, either a downward slope accelerated
      in the 1970s, or a rising trend was reversed.

PMID- 7513239
TI  - Lamellar organization of pontocerebellar neuronal populations. A multi-tracer and
      3-D computer reconstruction study in the cat.
AB  - This study deals with the three-dimensional arrangement of populations of
      pontocerebellar cell bodies projecting to the parafloccular complex. The
      fluorescent tracers rhodamine B isothiocyanate, fluoro-gold and fast blue were
      injected in either adjacent or separated cerebellar folia. A set of coordinates
      (x, y, z) was assigned to each retrogradely labelled cell and the total
      distribution reconstructed and displayed on a graphics workstation. At a large
      scale, we found that the majority of the cells of each labelled population (all
      projecting to the same folium) were confined to a lamella-shaped tissue volume.
      Each lamella extended from medial to lateral, and accordingly followed the
      curving of the pontine grey around the corticospinal and corticobulbar fibre
      tracts. At a smaller scale, i.e. within each lamellar subspace, the neurons
      belonging to one labelled population were distributed in aggregates of various
      shapes. To enable further analysis of the shapes of the intralaminar aggregates,
      we developed a computer program for unfolding of the lamellae, based on cubic B
      spline approximation. The flattened reconstructions were three-dimensional
      polygonal windows, circumscribing the large majority of the labelled cell swarm
      (usually 70-80% of the total number of labelled cells in one population). The
      present findings, taken together with previous data on a gradual, rather than
      disjunctive, shift of pontocerebellar neuronal position in relation to a gradual
      shift of target region (Bjaalie et al., Anat. Rec.,231, 510-523, 1991), suggest
      that the cerebropontocerebellar system may be organized according to a set of
      fairly simple topographic rules.

PMID- 7513240
TI  - Development of the thalamic reticular nucleus in ferrets with special reference
      to the perigeniculate and perireticular cell groups.
AB  - This study describes the development of the ferret thalamic reticular nucleus
      from Nissl-stained and from parvalbumin-immunostained sections. From early stages
      [embryonic day (E) 23-E25], there is a large group of ventral thalamic cells
      which lies between the dorsal thalamus and the primordial internal capsule. This
      group of cells, the primordial reticular nucleus, gives rise to the main body of
      the reticular nucleus, the perigeniculate nucleus and the perireticular nucleus.
      In the reticular nucleus, there are two waves of parvalbumin expression during
      development. The first wave begins prenatally in small cells which are seen
      rarely after birth. Their fate is not clear: they may have lost immunoreactivity,
      migrated elsewhere, or died. At the end of the first wave, a second wave begins
      in a distinct group of larger ovoid reticular cells, which appear to remain into
      adulthood. At about birth, the dorsocaudal pole of the reticular nucleus first
      forms the perigeniculate nucleus. During this developmental stage, cells which
      make up the reticular and perigeniculate nuclei are the only parvalbumin
      immunostained structures in the thalamus. Thus, rather than develop from the
      dorsal thalamus, the perigeniculate nucleus seems to have its origins in the
      ventral thalamus together with the reticular nucleus. During development, the
      reticular nucleus is associated closely with a large mass of cells located in the
      internal capsule, called the perireticular nucleus. Later, the perireticular
      nucleus is dramatically reduced in size: that is, there is a large reduction in
      the number of perireticular cells seen per section and in the extent of the
      nucleus across the internal capsule. There are two cytoarchitectonically distinct
      groups of perireticular cells. One group of cells, called the large-celled
      perireticular zone (LPR), enters the internal capsule from early prenatal
      development (E25). Many of these cells reach the globus pallidus and extend as
      far as the cortical subplate zone. The LPR together with the subplate form an
      extensive neuronal network in the white matter during early development, which
      disappears later in development (about postnatal day 20). The second group of
      perireticular cells is made up of smaller cells and is called the small-celled
      perireticular zone (SPR). These small cells enter the internal capsule from the
      reticular nucleus just prior to birth. Many of the cells in the SPR remain in the
      adult.

PMID- 7513241
TI  - Evidence for excitatory amino acid neurotransmitters in forward and feedback
      corticocortical pathways within rat visual cortex.
AB  - It is a commonly accepted notion that cells which make projections between the
      multiple cortical areas found in the mammalian visual system are excitatory, but
      there is little direct evidence that this is the case. Here we demonstrate using
      retrograde tracing with D-[3H]aspartate that connections in the rat which project
      from lower to higher visual areas (i.e. forward) and those which project from
      higher to lower areas (i.e. feedback) may use excitatory amino acid
      neurotransmitters. Following injection into the primary visual cortex, clusters
      of retrogradely labelled cells were found in several extrastriate areas within
      the cytoarchitectonic subdivisions 18a ('areas' LM, AL, PX, FLX, RL, AX) and 18b
      ('area' MX), and in the retrosplenial cortex. In all of these areas D
      [3H]aspartate-labelled cells were surrounded by diffuse label which may represent
      anterograde labelling of axon terminals. This suggests that both legs of
      reciprocal intracortical circuits have similar chemospecificity. To directly
      demonstrate excitatory amino acid localization in forward projections, D
      [3H]aspartate was injected into extrastriate area LM. As expected, the results
      revealed retrogradely labelled neurons within area 17. Outside area 17, LM
      injections labelled neurons in AL, PX, FLX, RL, AX and MX. Taken in the context
      of the hierarchy of areas in rat cerebral cortex (Coogan and Burkhalter, J.
      Neurosci., 13, 3749-3772, 1993), these results show that D-[3H]aspartate labels:
      (1) forward connections from area 17 to LM, AL, PX, RL, AX and MX, (2) feedback
      connections from LM, AL, FLX, PX, RL, AX and MX to area 17, (3) feedback
      connections from AL, PX, RL, AX and MX to LM, and (4) lateral connections between
      FLX and LM. These findings strongly indicate that both forward and feedback
      connections as well as lateral connections at several different levels of the
      cortical hierarchy use excitatory amino acid neurotransmitters.

PMID- 7513242
TI  - Molecular tools for the identification of ectomycorrhizal fungi--taxon-specific
      oligonucleotide probes for suilloid fungi.
AB  - Five taxon-specific oligonucleotide probes are described that can be used to help
      identify the fungal components of ectomycorrhizae. Comparisons among partial
      sequence from the mitochondrial large subunit rRNA gene (mt-LrRNA) were used to
      select the probes, which were intended to be specific to several taxa within the
      suilloid group of the Boletales (Basidiomycota). Probes S1, R1, and G1 were
      targeted at the genera Suillus, Rhizopogon and Gomphidius; probe G2 was designed
      to recognize the family, Gomphidiaceae, and probe US1 was designed to recognize
      all of these taxa and any other members of the suilloid group. The specificity of
      each probe was determined empirically by testing their ability to hybridize to
      PCR amplified fragments derived from 84 species of basidiomycetes. Although none
      of the probes exhibited their intended specificity, all specifically hybridized
      to useful subsets of taxa, and collectively they can be used to identify many
      suilloid taxa to the generic level or below. The probes were also tested for
      their ability to identify field collected mycorrhizae and were found to perform
      well.

PMID- 7513243
TI  - Isolation and sequence analysis of peptides from the venom of Protonectarina
      sylveirae (Hymenoptera-Vespidae).
AB  - Three new venom peptides were isolated from the Brazilian wasp; Protonectarina
      sylveirae and their complete amino acid sequences were determined by Edman
      degradation as well as by FAB-mass spectrometry. One (P-8) of them was a new
      analog of mastoparan family; therefore, we named it Protonectarina mastoparan.
      Another peptide (P-10) had an amino acid sequence homology with Ves-CP-T, a
      chemotactic peptide of wasp venom, and bombolitin-V, the venom peptide from
      bumblebee. The third peptide (P-6) was structurally unique, possessing an
      intramolecular disulfide bond. Not only Protonectarina mastoparan (P-8) but also
      P-6 and P-10 caused histamine release from rat peritoneal mast cells as potently
      as mastoparan (EC50s were about 1 x 10(-6) M for P-6 and 2 x 10(-6) M for P-10).
      In addition, P-10 in a concentration higher than 1 x 10(-5) M induced hemolysis
      though whose hemolytic activity was about a half potency of that of mastoparan.
      However, P-6 did not cause hemolysis up to the concentration of 10 microM. We
      have named them sylverin for the peptide P-6 and protonectin for the peptide P
      10.

PMID- 7513244
TI  - Expression of hepatitis C virus in hepatocellular carcinoma.
AB  - BACKGROUND: Epidemiologic studies have suggested a strong association between
      chronic hepatitis C virus (HCV) infection and the development of hepatocellular
      carcinoma (HCC). To investigate the possible role of HCV in the pathobiology of
      HCC, the authors studied the expression of HCV in 10 cases of HCC with chronic
      HCV infection. METHODS: The core, envelope, and nonstructural (NS) 3 and 5
      proteins were localized in liver and tumor tissues by the immunoperoxidase
      technique using mouse monoclonal antibodies to recombinant proteins or synthetic
      peptide of HCV. In addition, the positive and negative strands of HCV RNA were
      detected in the tissues by strand-specific reverse transcription/double
      polymerase chain reaction using primers for the 5'-nontranslated region. RESULTS:
      The HCV proteins were expressed in three of nine HCC specimens tested (the core
      protein in three HCC, the envelope, NS3 and NS5 proteins in one HCC) and in two
      of nine nontumorous liver specimens adjacent to the HCC (the core protein in two
      specimens, envelope, NS3 and NS5 proteins in one specimen). Positive-stranded HCV
      RNA was detected in all tumorous and nontumorous specimens except in one tumor.
      Negative-stranded HCV RNA was found in six of nine HCC tested and in all
      nontumorous livers. CONCLUSIONS: These findings suggest that HCV persists in
      hepatocytes during malignant transformation, although secondary infection of
      tumor cells by HCV cannot be excluded. Some HCC appear to support replication and
      expression of HCV.

PMID- 7513245
TI  - Hepatocellular carcinoma after transcatheter hepatic arterial embolization. A
      histopathologic study of 84 resected cases.
AB  - BACKGROUND: Recently, transcatheter arterial embolization (TAE) has been used to
      treat hepatocellular carcinoma (HCC), yet much is still unknown regarding its
      optimal use. METHODS: Eighty-four patients with HCC after TAE underwent surgical
      resection. Fifty of the tumors were less than 3 cm (small HCC [S-HCC]), and 34
      were 3 cm or larger (large HCC [L-HCC]). Necrosis rate, distribution of residual
      HCC, histopathology of the main tumor, and proliferating activity of residual HCC
      by means of proliferative cell nuclear antigen (PCNA) were examined. Twenty-two
      randomly selected patients with HCC treated with standard chemotherapy were used
      as non-TAE control subjects. RESULTS: A necrosis rate of greater than 95% was
      seen in 35 cases of S-HCC and in 15 of L-HCC. All five nonencapsulated tumors
      were L-HCC and had a much lower necrosis rate. No tumors in the control group
      showed a necrosis rate of greater than 95%. Encapsulated tumors were categorized
      according to their tumor interiors, capsules, and extracapsular zones. Complete
      necrosis of the tumor interior was 80.0% and 35.3% in S-HCC and L-HCC,
      respectively. Viable residual tumors were found mainly in the extracapsular zone
      in S-HCC, whereas in L-HCC they were located primarily in the tumor interior.
      Most capsules were affected by tumor necrosis and the subsequent healing process,
      resulting in a thick secondary capsule. Tumor interior necrosis was uniform and
      coagulative in S-HCC, in contrast to L-HCC, in which necrotic regions comprised
      several necrosis units of differing texture and were divided by fibrous septa. In
      contrast, the control group revealed spotty, sparse necrosis. Non-TAE tumor
      capsules were thin and pathologically characteristic of those naturally occurring
      in tumors, as opposed to the thick fibrous capsules, which are inducible by TAE
      therapy. In the TAE group, the PCNA positivity rates were 37.5%, 52.5%, and 100%
      in Grades 1, 2, and 3/4 combined, respectively. At the tumor-nontumor boundary of
      the extracapsular region, PCNA-positive cells were detected in 55.0% of the
      cases. CONCLUSIONS: The thickened tumor capsule serves as a good postoperative
      indicator of TAE response. Small tumors seem to be affected in the tumor
      interior, whereas extracapsular invasion undermines the TAE effect. PCNA was
      helpful in detecting the tumor-nontumor boundary and useful as a parameter of
      viability of HCC after TAE.

PMID- 7513246
TI  - Prognostic significance of proliferating cell nuclear antigen expression in
      hepatocellular carcinoma.
AB  - BACKGROUND: Proliferating cell nuclear antigen (PCNA) is a nuclear protein
      synthesized in G1/S-phase of the cell cycle and therefore is related to cell
      proliferative activity. In an attempt to evaluate its prognostic significance and
      clinicopathologic correlation in patients with hepatocellular carcinoma (HCC),
      the proliferative activity was studied using immunohistochemical staining with
      monoclonal antibody to PCNA. METHODS: Seventy-two patients (64 men, 8 women; mean
      age, 52 years [range, 24-77 years]) having HCC surgically resected were studied.
      Tumor and nontumor tissues were selected from each case and stained with PCNA
      antibody. Tumor and nontumor PCNA (T-PCNA and NT-PCNA) scores were assessed by
      counting the positive staining nuclei per 1000 cells. RESULTS: The T-PCNA score
      ranged from 10 to 894 per 1000 cells (mean +/- standard deviation = 333 +/- 263).
      It was found to be significantly and positively associated with positive margin
      (P = 0.003), direct liver invasion by tumor (P = 0.021), and venous permeation (P
      = 0.020), features directly or indirectly related to tumor invasiveness. However,
      it had no significant association with tumor size, cellular differentiation, or
      patients' hepatitis B surface antigen (HBsAg) status. When the tumors were
      stratified into two groups with a T-PCNA score less than or equal to 200 and a T
      PCNA score greater than 200, those patients with a T-PCNA score less than or
      equal to 200 had significantly longer disease-free survival (DFS) and actual
      survival (AS) rates than those with scores greater than 200 (median DFS and AS,
      34.6 and 49.3 months and 7.7 and 19.1 months, respectively; P = 0.019 and 0.035
      for DFS and AS, respectively). T-PCNA and NT-PCNA scores had no significant
      correlation with the HBsAg status of the patients. CONCLUSIONS: Proliferative
      activity in HCC, as defined by PCNA immunohistochemical analysis, is
      significantly related to tumor invasiveness. It is also a potentially valuable
      prognostic factor in patients with this tumor.

PMID- 7513247
TI  - Plasma transforming growth factor-beta 1 in patients with hepatocellular
      carcinoma. Comparison with chronic liver diseases.
AB  - BACKGROUND: Many kinds of human malignant tissue, including hepatocellular
      carcinoma (HCC), were reported to overexpress transforming growth factor-beta 1
      (TGF-beta 1) gene. However, little work has been done on the circulating TGF-beta
      1 in patients with malignant tumors. METHODS: Plasma TGF-beta 1 levels in
      patients with HCC (n = 26) were compared with those in patients with chronic
      hepatitis (CH) (n = 12) and cirrhosis (n = 11) and in normal subjects (n = 20)
      using an enzyme-linked immunosorbent assay system after acid/ethanol extraction.
      RESULTS: The patients with HCC had significantly higher plasma TGF-beta 1 levels
      (19.3 +/- 19.5 ng/ml; mean +/- standard deviation [SD]) than those in normal
      subjects (1.4 +/- 0.8 ng/ml) and in patients with CH (3.0 +/- 3.1 ng/ml) and
      cirrhosis (3.7 +/- 2.1 ng/ml) (P < 0.01). Plasma TGF-beta 1 concentrations in the
      patients with cirrhosis were also significantly higher than those in the normal
      subjects (P < 0.05). The extracted plasma TGF-beta 1 from the patients with HCC
      had biologic activity according to a growth inhibitory assay using mink lung
      epithelial cells. No significant correlation was found between the plasma TGF
      beta 1 levels in the patients with HCC and serum alpha-fetoprotein levels. After
      successful treatment for HCC, the amount of plasma TGF-beta 1 significantly
      decreased from 22.6 plus or minus 16.7 ng/ml (mean +/- SD) to 10.2 plus or minus
      6.5 ng/ml (P < 0.05). CONCLUSIONS: We demonstrated higher levels of plasma TGF
      beta 1 in the patients with HCC than those in patients with chronic hepatitis and
      cirrhosis. Plasma TGF-beta 1 might be a candidate for a novel tumor marker for
      hepatocellular carcinoma.

PMID- 7513248
TI  - Expression of acinar and ductal products in Capan-1 cells growing in synthetic
      serum and serum-free media.
AB  - BACKGROUND: Capan-1 is a human pancreatic adenocarcinoma cell line of presumed
      ductal origin. This is based on the histologic appearance of the tumor from which
      it arose. Yet considerable controversy exists regarding the actual cell of origin
      for these exocrine carcinomas. Two acinar antigens, ribonuclease and trypsin,
      were analyzed in cells growing in synthetic serum. METHODS: Capan-1 cells were
      adapted to grow in basal medium supplemented with synthetic serum, because fetal
      bovine serum (FBS) normally used to culture cells contains bovine ribonuclease,
      which can interfere with measurements of the ribonuclease secretion. These cells
      were also adapted to grow in different serum-free media, allowing us to determine
      its minimal growth requirements. The presence of ribonuclease in Capan-1 and PANC
      1 conditioned media was monitored by activity. Other acinar and ductal markers
      were monitored using Northern blot analysis. RESULTS: Capan-1, PANC-1, IBF-CP3,
      and MDAAmp-7 cell lines were successfully adapted to grow in synthetic serum by
      means of the adaptation protocol reported here. The adaptation of Capan-1 to
      serum-free media showed that the cells are capable of growing in a medium
      containing insulin, transferrin, selenium, a nonprotein carrier, and lipoic and
      linoleic acids. Northern blot analysis showed the expression of carbonic
      anhydrase II, cytokeratin 18, ribonuclease, and trypsin in Capan-1 cells growing
      in FBS and synthetic serum. No changes in morphology, karyotype, or gene
      expression were observed in these cells as a result of the adaptation process.
      CONCLUSION: The cell line Capan-1 is expressing some ductal as well as acinar
      products despite its supposed ductal origin. The expression of trypsin at the
      mRNA level and ribonuclease at mRNA and protein levels is shown in Capan-1 cells.
      The protein expression will be further investigated as the cell line has been
      adapted to grow in synthetic serum and serum-free media with no apparent changes
      with respect to their growth in FBS.

PMID- 7513249
TI  - Heterogeneous expression of nm23 gene product in noninvasive breast carcinoma.
AB  - BACKGROUND: The two major types of noninvasive breast carcinoma, ductal carcinoma
      in situ (DCIS) and lobular carcinoma in situ (LCIS), are quite different in their
      histopathologic appearance and clinical implications. LCIS is only a marker of an
      increased risk of later development of invasive carcinoma, whereas most DCIS
      lesions are at least nonobligate precursors of invasive carcinoma. DCIS is a
      heterogeneous group of lesions composed of several distinct subtypes, with only
      the comedo subtype having immediate malignant potential. The authors' purpose was
      to analyze noninvasive carcinomas for the presence of a gene product (nm23)
      indicative of a favorable prognosis in invasive carcinomas to determine
      differences (1) among the different types of CIS and (2) in CIS with and without
      an accompanying invasive component. METHODS: Immunohistochemical methods were
      used to detect nm23 gene product in archival material from two groups of
      patients: Group 1 consisted of 54 cases of purely noninvasive carcinoma, and
      Group 2 consisted of 55 examples of noninvasive carcinoma associated with an
      invasive component. RESULTS: Among the cases of CIS with no invasion, LCIS and
      comedo DCIS expressed more nm23 than noncomedo DCIS (P < or = 0.03). There were
      no differences among these CIS subtypes in the group with invasion. Comparing
      subtypes of CIS in the groups with or without invasion, only comedo DCIS was
      significantly different, with greater expression in the CIS group with no
      invasion compared with comedo DCIS associated with an invasive component (P =
      0.04). CONCLUSIONS: These results support the special nature of LCIS and the
      heterogeneous nature of DCIS. The in situ component attending an invasive
      component may be different from anatomically similar lesion without associated
      invasion. The absence of nm23 in comedo DCIS may be indicative of invasive
      capacity.

PMID- 7513250
TI  - Bone metastasis from cervical cancer.
AB  - BACKGROUND: This retrospective analysis examines the frequency, distribution, and
      the pattern of disease progression of bone metastasis in patients treated for
      cervical cancer and the use and results of palliative intent radiation therapy.
      METHODS: Charts, films, and other available records were reviewed for the 41
      patients with bone metastasis of the 496 patients with invasive cervical cancer
      treated at the Gershenson Radiation Oncology Center, Detroit, Michigan, from 1980
      through 1989. RESULTS: Several patterns of bone metastasis were observed: (1)
      direct extension into bone from the parametrial extensions of the primary or
      recurrent pelvic tumor, (2) direct extension into bone from parenchymal
      metastasis to distant lymph nodes or lung, (3) regional hematogenous metastasis
      compatible with Batson's venous plexus distribution, and (4) systemic
      hematogenous metastasis to distant bones. Eighty percent of the patients were
      irradiated, and of those, 70% experienced pain relief. CONCLUSIONS: Bone
      metastasis in patients with cervical cancer is an infrequent but significant
      occurrence with associated severe dysfunction, other signs of local and distant
      failure, and short life expectancy. Radiation therapy provides moderate
      palliation for treatable patients.

PMID- 7513251
TI  - Intermediate-grade lymphomas treated with cyclophosphamide-doxorubicin-
      vincristine-prednisone-bleomycin alternated with cyclophosphamide-methotrexate
      etoposide-dexamethasone. Application of prognostic models to data analysis.
AB  - BACKGROUND: Numerous treatment strategies have been tried with the aim of
      improving results for patients with intermediate-grade lymphomas (IGL) over those
      achieved with cyclophosphamide, doxorubicin, vincristine, prednisone, and
      bleomycin (CHOP-Bleo), and numerous prognostic models have been developed to
      identify and separate risk groups. This study reports on a new protocol for Ann
      Arbor Stages II-IV IGL that consists of CHOP-Bleo alternated with a new regimen
      of cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED) and
      radiation therapy and demonstrates the usefulness of prognostic models for
      identifying risk groups and comparing treatment programs. METHODS: One hundred
      seventy patients with Ann Arbor Stages II-IV IGL were treated with alternating
      cycles of CHOP-Bleo and CMED for a total of 12 cycles. Involved field radiation
      therapy was interspersed with courses of chemotherapy for patients with Stage II
      and Stage III disease. Results were analyzed and compared with those of the
      authors' previous study of CHOP-Bleo and radiation therapy using the Ann Arbor
      staging system, their earlier prognostic model, and the recently published
      International Index. RESULTS: A complete remission occurred in 78% of the
      patients. The overall 5-year survival rate was 67%. Survival was better for
      patients with Ann Arbor Stage II disease (80%) than for those with Stage III or
      Stage IV (67% and 58%, respectively). High tumor burden, above-normal levels of
      serum lactic dehydrogenase, serum beta 2-microglobulin, and Ann Arbor Stage IV
      disease were adverse factors. The International Index and the authors' earlier
      prognostic model separated four prognostic groups. CHOP-Bleo/CMED was generally
      well tolerated. Neutropenic fever was the major complication that occurred in 25
      patients during treatment. Six of these patients died of sepsis. CONCLUSIONS:
      This study demonstrated that CHOP-Bleo/CMED is a well-tolerated regimen that
      produced better results than those reported for a former study that used CHOP
      Bleo alone. Further, results for CHOP-Bleo/CMED compared favorably with those of
      other second- and third-generation regimens. The study also validated the
      usefulness of prognostic models and, in particular, the new International Index
      for identifying risk groups.

PMID- 7513253
TI  - Characterization of tumor-associated neural cell adhesion molecule in human
      serum.
AB  - In human serum, at least two molecular species of the neural cell adhesion
      molecule (NCAM) with molecular weights of 110,000-130,000 and 150,000-180,000,
      respectively, can be identified by Western blotting. Both are characterized by
      the absence of epitopes for monoclonal antibodies KD11 and MG5, which
      specifically recognize intracellular domains of the human NCAM transmembrane
      isoforms, NCAM-140 and NCAM-180. In contrast to the M(r) 110,000-130,000 molecule
      also detectable in serum samples from healthy blood donors, the M(r) 150,000
      180,000 molecule appears to be tumor associated. The only difference between
      these two species is shown to be the presence of long chains of alpha-(2,8)
      linked N-acetylneuraminic acids, which are characteristic for the so-called
      embryonic NCAM form. After treatment with endoneuraminidase N, the M(r) 150,000
      180,000 molecule can no longer be discriminated from the M(r) 110,000-130,000
      molecule in Western blotting as well as gel and anion exchange chromatography
      experiments. The experimental data clearly show that only the embryonic NCAM
      molecule carrying the poly-alpha-(2,8)-linked N-acetylneuraminic acid moiety can
      be regarded as a specific serum marker for small cell lung cancer.

PMID- 7513252
TI  - Differential regulation of folate receptor isoforms in normal and malignant
      tissues in vivo and in established cell lines. Physiologic and clinical
      implications.
AB  - BACKGROUND: Despite significant differences in ligand binding between the two
      known isoforms of the human membrane folate receptor (FR), designated herein as
      FR-beta (placenta) and FR-alpha (placenta, KB cells), little is known about their
      tissue specificities, and there is no report on the relative expression of FR
      beta in any tissue other than in placenta. METHODS: The mRNA for each FR isoform
      in a wide variety of normal fetal and adult tissue explants, primary normal cell
      cultures, malignant tumor explants, and established tumor cell lines was
      estimated by a polymerase chain reaction assay. Total receptor levels were
      estimated by a [3H] folic acid binding assay. RESULTS: Both the FR isoforms were
      expressed in fetal as well as adult tissues. Normal tissues generally expressed
      low to moderate amounts of FR-beta. FR-alpha alone was expressed in normal
      epithelial cells and was frequently strikingly elevated in a variety of
      carcinomas, with the exception of squamous cell carcinomas of the head and neck.
      In contrast, a variety of malignant tissues of nonepithelial origin generally
      expressed elevated levels of FR-beta alone. Established tumor cell lines
      expressed FR-alpha virtually alone and did not reflect FR expression patterns in
      vivo. KB cells and JEG-3 cells grown at low folate concentrations further up
      regulated FR-alpha but not FR-beta. CONCLUSIONS: Although FR-beta is the more
      common isoform, FR-alpha and FR-beta are differentially regulated in normal
      tissues, carcinomas, nonepithelial malignancies, and immortalized cells or in
      response to changes in extracellular folate concentrations. The tissue
      specificity of FR isoforms and their elevation in malignant tissues may be a
      significant factor in FR-mediated folate uptake, in tissue responsiveness to
      promising novel antifolates, and in FR-related immunodiagnosis/immunotherapy.

PMID- 7513254
TI  - Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell
      binding of basic fibroblast growth factor, migration, proliferation, and
      induction of urokinase-type plasminogen activator.
AB  - Suramin, an anticancer agent in current clinical trials, is a prototype of a
      pharmacological antagonist of growth factors, including basic fibroblast growth
      factor (bFGF). Suramin inhibited angiogenesis in the chick chorioallantoic
      membrane assay in a dose-dependent fashion. Suramin, 200 mg/kg i.v., inhibited
      rat corneal angiogenesis induced by bFGF-impregnated polymers; addition of
      heparin stimulated angiogenesis and counteracted the inhibition of suramin. The
      half-maximal inhibitory concentration (IC50) of suramin was determined for key
      cellular mechanisms that regulate angiogenesis: (a) low and high affinity
      cellular binding of bFGF to bovine capillary endothelial (BCE) cells with IC50s,
      respectively, of 24.3 and 71.5 micrograms/ml; (b) spontaneous migration of bovine
      pulmonary artery endothelial and normal AG 7680 fetal bovine aortic endothelial
      cells; bFGF-stimulated migration of BCE and transformed GM 7373 fetal bovine
      aortic endothelial cells with IC50s of 200-320 micrograms/ml; (c) proliferation
      of bovine pulmonary artery endothelial cells at > 100 micrograms/ml and of BCE
      cells at > 250 micrograms/ml; and (d) urokinase-type plasminogen activator
      activity of GM 7373 endothelial cells stimulated by bFGF with an IC50 of 211
      micrograms/ml and of BCE cells stimulated by bFGF at > 100 micrograms/ml, but not
      plasminogen activator activity induced by phorbol 12-myristate 13-acetate.
      Suramin inhibited multiple control points of angiogenesis, including those
      stimulated by bFGF. Because tumor growth is angiogenesis dependent, the clinical
      efficacy of suramin may relate, in part, to angiosuppression.

PMID- 7513255
TI  - Cytotoxic T-lymphocyte response to autologous human squamous cell cancer of the
      lung: epitope reconstitution with peptides extracted from HLA-Aw68.
AB  - Cytotoxic T-lymphocytes (CTLs) specific for autologous human squamous cell cancer
      of the lung were generated by stimulation of peripheral blood lymphocytes with
      autologous tumor cells in vitro. The CTL line was >97% CD3+, CD8+, CD16- and
      produced tumor necrosis factor-alpha, gamma-interferon, and granulocyte
      macrophage colony-stimulating factor after stimulation with autologous tumor. The
      CTLs lysed autologous tumor but failed to recognize autologous or
      histocompatibility leukocyte antigen-matched lymphoid cells, K562, or allogeneic
      tumor cells of several histological types. Antibody-blocking studies suggested
      that the CTLs recognized one or more antigens presented by the class I major
      histocompatibility complex molecule Aw68. To characterize these antigens further,
      histocompatibility leukocyte antigen Aw68 molecules were extracted from the
      squamous cell cancer of the lung tumor line by immunoaffinity chromatography, and
      the associated peptides were eluted in acid and separated by reversed-phase high
      performance liquid chromatography. Reconstitution of the CTL epitope was
      evaluated by adding these peptides to autologous Epstein-Barr virus-transformed B
      cells. Two peaks of reconstituting activity were observed, suggesting that these
      CTLs recognize at least two Aw68-associated peptides. This study confirms the
      existence of a CTL response against autologous human squamous cell cancer of the
      lung and suggests that this CTL response is directed against peptide epitopes
      presented by the class I major histocompatibility complex molecules. It is
      anticipated that this approach will permit identification of peptide epitopes for
      lung cancer-specific CTLs.

PMID- 7513256
TI  - Neovascularization in clinical stage A testicular germ cell tumor: prediction of
      metastatic disease.
AB  - Increased numbers of blood vessels (angiogenesis or neovascularization) in
      certain primary tumors correlates with an increased risk for metastatic disease.
      We therefore conducted a blinded review of the resected testicular germ cell
      tumors of 65 clinical stage A patients to evaluate the usefulness of angiogenesis
      in identifying those patients with clinically occult nodal metastases
      (pathological stage B). Angiogenesis was assessed in the primary tumors using an
      immunohistochemical stain for factor VIII-related antigen assay for quantitation
      of microvessel counts. Of 65 clinical stage A patients, 43 had pathological stage
      B disease at retroperitoneal lymph node dissection. Eleven patients had
      microvessel counts > 30 microvessels/x 400 high powered field, and all of these
      patients had pathological stage B disease (P = 0.02 in univariate analysis).
      Multiple regression analysis using microvessel count and other histological
      findings found to be prognostic (venous invasion, lymphatic invasion, presence of
      embryonal carcinoma, and absence of yolk sac tumor) showed that only the absence
      of a yolk sac tumor component was significantly predictive of occult metastases.
      This study shows that angiogenesis, as measured by quantitation of microvessel
      counts in the primary tumor of germ cell neoplasms, is significantly predictive
      of occult nodal metastatic disease by univariate analysis in clinical stage A
      patients. The prospective use of angiogenesis quantitation needs to be defined.

PMID- 7513257
TI  - Complexes of yeast RNA polymerase II and RNA are substrates for TFIIS-induced RNA
      cleavage.
AB  - In the absence of DNA, purified yeast RNA polymerase II can bind RNA to form a
      binary complex. RNA in such RNA-RNA polymerase complexes undergoes reactions
      previously thought to be unique to nascent RNA in ternary complexes with DNA,
      including TFIIS-dependent cleavage and elongation by 3'-terminal addition of NMP
      from NTP. Both of these reactions are inhibited by alpha-amanitin. Hence, by
      several criteria the RNA in binary complexes is bound to the polymerase in a
      manner quite similar to that in ternary complexes in which the catalytic site for
      nucleotide addition is positioned at or near the 3'-OH terminus of the RNA. These
      findings are consistent with a model for the RNA polymerase ternary complex in
      which the RNA is bound at the 3' terminus through two protein-binding sites
      located up to 10 nt apart.

PMID- 7513258
TI  - A multifunctional docking site mediates signaling and transformation by the
      hepatocyte growth factor/scatter factor receptor family.
AB  - Signaling by tyrosine kinase receptors is mediated by selective interactions
      between individual Src homology 2 (SH2) domains of cytoplasmic effectors and
      specific phosphotyrosine residues in the activated receptor. Here, we report the
      existence in the hepatocyte growth factor/scatter factor (HGF/SF) receptor of a
      multifunctional docking site made of the tandemly arranged degenerate sequence
      YVH/NV. Phosphorylation of this site mediates intermediate- to high-affinity
      interactions with multiple SH2-containing signal transducers, including
      phosphatidylinositol 3-kinase, phospholipase C gamma, pp60c-src, and the GRB-2
      Sos complex. Mutation of the two tyrosines results in loss of biological
      function, as shown by abrogation of the transforming activity in the oncogenic
      counterpart of the receptor. The same bidentate motif is conserved in the
      evolutionarily related receptors Sea and Ron, suggesting that in all members of
      the HGF/SF receptor family, signal transduction is channeled through a
      multifunctional binding site.

PMID- 7513259
TI  - Effects of aging on natural killer cell activity and activation by interleukin-2
      and IFN-alpha.
AB  - To address the conflicting reports concerning both innate and lymphokine
      inducible NK activity of elderly individuals, NK activity of peripheral blood
      mononuclear cells (PBMC) of 21 young (23 to 35 years old) and 43 elderly (65 to
      100 years old) subjects was assessed using a 4-hr chromium release assay with
      K562 or Daudi cells as targets. Significantly higher innate NK cell activity was
      observed in elderly compared to young individuals (P < 0.001, Student t test). NK
      activity of both groups was enhanced to the same degree by IL-2. Although
      intermediate amounts of IFN-alpha (100-500 mu/10(6) cells) induced comparable
      maximal NK activity of both young and elderly subjects, young subjects responded
      better than elderly to low amounts of IFN-alpha (10 mu/10(6) cells), while higher
      amounts (10(3) mu/10(6) cells) reduced the NK activity of the elderly, but not
      young, to basal levels. IFN-alpha also expanded the range of target cells
      susceptible to NK activity. Untreated cells of neither young nor elderly showed
      activity against Daudi targets. Two-hour treatment with IFN-alpha resulted in
      significant activity against Daudi cells; however, this activity was
      significantly lower in the elderly compared to the young subjects.

PMID- 7513260
TI  - Expression of a membrane form of the pregnancy-associated protein TJ6 on
      lymphocytes.
AB  - TJ6 is a novel protein which has immunosuppressive activity and may have a
      functional role in fetal allograft survival during pregnancy. Initial studies
      indicated that when mice were treated with an anti-TJ6 binding mAb early in
      pregnancy, the pregnancies were completely ablated and that TJ6 expression is
      enhanced dramatically during pregnancy. In addition we have cloned the cDNA for
      TJ6 which encodes a possible transmembrane domain that may include six to seven
      transmembrane regions. Therefore, we examined TJ6 expression on PBL of pregnant
      and non-pregnant women and found that TJ6 is expressed primarily on CD19+ B cells
      from pregnant but not nonpregnant women. TJ6 was not expressed on CD3+
      lymphocytes from either group but was expressed on CD56+ cells from a small
      population of pregnant women which preliminary data indicate may correlate with
      the occurrence of spontaneous abortion in these women. Here we also show that TJ6
      transcripts are highly expressed in the developing fetoplacental unit as well as
      in the developing thymus. We also begin to characterize the expression of TJ6
      isoforms in an acute lymphocytic leukemia cell line (SB), murine thymus, and the
      developing murine fetoplacental unit, as well as the expression of a membrane
      form of TJ6 present on human lymphocytes during pregnancy. All of these cells and
      tissues expressed TJ6 proteins which were smaller than predicted based on either
      the cDNA sequence or the in vitro translation even though they expressed mRNA
      similar in size. The TJ6 isoforms varied in size from the 45-kDa isoform in SB
      cells to the 52-kDa isoform of the fetoplacental unit to a 70-kDa isoform in
      murine thymus. Flow cytometric analysis also demonstrated that similar to the
      CD19+ B cells from pregnant women, TJ6 is expressed on the surface of SB cells.

PMID- 7513261
TI  - Control of lymphocyte integrin function: evidence for multiple contributing
      factors.
AB  - The control of lymphocyte adhesion is critical for proper cellular functions. The
      alpha 2 beta 1 integrin complex serves as a receptor for collagen on lymphocytes.
      The T cell leukemia Jurkat expresses alpha 2 beta 1 in a latent form on the cell
      surface. Three types of stimuli, antibody to the alpha 2 chain (JBS2), antibody
      to the beta 1 chain (JB1B), and phorbol ester (PMA), each induce activation of
      alpha 2 beta 1-dependent Jurkat binding to collagen. A comparison of the JBS2,
      JB1B, and PMA induction requirements indicated that the JB1B and the JBS2 effects
      are not sensitive to staurosporine while the PMA response is completely
      inhibited. Combinations of functionally saturating concentrations of the stimuli
      displayed an additive effect. Collectively these results suggest that several
      factors contribute to the generation of full integrin functionality and cellular
      adhesion, thus providing a possible basis for incrementally controlling the
      adhesive potential of lymphoid cells.

PMID- 7513262
TI  - In vitro expansion of tumor-specific, HLA-restricted human CD8+ cytolytic T
      lymphocytes.
AB  - The effect of cytokines with human recombinant interleukin-2 (rIL-2) on cytolytic
      T cell (CTL) generation was studied. Lymphocytes were isolated from involved
      lymph nodes of melanoma patients and expanded in medium containing rIL-2 alone or
      in combination with other human cytokines (rIL-1, rIL-4, rIL-6, and recombinant
      human tumor necrosis factor-alpha (rTNF alpha)). Lymphocytes incubated with rIL-2
      alone did not grow, whereas addition of the other cytokines augmented IL-2
      mediated lymphocyte proliferation. In all cultures, the majority of expanded
      lymphocytes were CD3+, CD56- T cells. Lymphocytes cultured with rIL-1, rIL-2, rIL
      4, and rIL-6 exhibited cytolytic activity specific for autologous melanoma, which
      increased during the culture period (24.08 and 58.18% at 16 and 30 days in
      culture, respectively) without detectable changes in cell surface phenotype and
      remained high even after 100 days in culture. Moreover, the cytolytic activity
      was inhibited by monoclonal antibodies (mAbs) against HLA-class I, CD3, and CD8
      molecules but not by mAbs against HLA-class II or CD4 molecules. Lymphokine
      activated killer (LAK) activity was detected in lymphocytes cultured with rIL-1,
      rIL-2, and rIL-6 in the presence or absence of rTNF alpha. These data indicate
      that lymphocytes derived from melanoma-invaded lymph nodes and cultured in the
      presence of rIL-1, rIL-2, rIL-4, and rIL-6 offers an efficient system to expand
      CD8+ CTLs with HLA-restricted cytolytic specificity against autologous tumor
      cells.

PMID- 7513263
TI  - Relationship between nuclear ribonucleoprotein arrangement and cell proliferation
      in Burkitt lymphoma cells.
AB  - The presence of body-like structures in nuclei from interferon alpha-treated
      Daudi cells has been shown on the ultrastructural level, by the use of different
      staining methods. The degree of their rearrangement in the nucleoplasm seems to
      be dependent on the time of interferon treatment. Since this morphological
      evidence has been found to be preceded by a slowing down of RNA transcriptional
      machinery early upon the interferon administration, it is speculated that
      interferon generated signals might lead to RNP granule accumulation in the
      nucleus and a consequent arrangement into defined structures.

PMID- 7513264
TI  - Preparation of a monoclonal antibody and expression of its antigen associated
      with myogenic differentiation on spontaneous and artificial myotubes derived from
      avian myoblasts.
AB  - Quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma
      virus (ts-RSV) proliferate and do not differentiate at 35.5 degrees C, the
      permissive temperature for the virus, whereas their myoblast differentiation
      proceeds at 41.0 degrees C, a non-permissive temperature. In this experimental
      system, myogenic differentiation is controlled by src gene products. Using QM-RSV
      cells as an antigen, a monoclonal antibody, Mb-N3, was prepared. Expression of Mb
      N3 antigen was found to increase during differentiation. Therefore, in studies on
      the mechanism of myogenic differentiation, we examined the expression of Mb-N3
      antigen on spontaneously forming myotubes formed at 41.0 degrees C and fused
      myoblasts with hemagglutinating virus of Japan (HVJ, Sendai virus) disregarding
      programmed processes for myogenic differentiation. When the myoblasts cultured at
      35.5 degrees C were treated with HVJ, they fused with each other. These fused
      myoblasts were elongated and were morphologically similar to spontaneously
      forming myotubes. Thus, we called fused myoblasts with HVJ "artificial myotubes."
      During culture at 35.5 degrees C, the artificial myotubes did not show increased
      expression of Mb-N3 antigen and increase of creatine kinase activity, which are
      markers of normal biochemical differentiation. When artificial myotubes were
      cultured at 41.0 degrees C, expression of Mb-N3 antigen and creatine kinase
      activity increased. These results suggest that the expression of the antigen is
      regulated by kinase activity derived from src gene products even after compulsory
      cell fusion. Moreover, compulsory fusion does not cause myogenic differentiation
      and expression of Mb-N3 antigen. Thus it seems that the differentiation program
      must proceed in order for myogenic differentiation and expression of Mb-N3
      antigen to take place.

PMID- 7513265
TI  - In situ assay of basic fibroblast growth factor in cultured cells with a specific
      monoclonal antibody.
AB  - The localization of basic fibroblast growth factor (bFGF) in various cultured
      bFGF-producing cells, including bovine capillary endothelial (BCE) cells and
      human cholangiocellular carcinoma (HuCC-T1) cells, was determined by measuring
      binding of 125I-labeled specific monoclonal antibody against bFGF. bFGF on the
      cell surface and within the cells was determined by counting the radioactivity of
      the labeled monoclonal antibody bound to the cells before and after increasing
      their permeability by treatment with alcohol or Triton X-100. The radioactivity
      bound to these cells decreased with increase in the concentration of unlabeled
      monoclonal antibody. Scatchard analyses of these data suggested the quantitative
      localization of bFGF and Kd values showing the specific binding. This method was
      designated as in situ assay with radio-labeled antibody (ISARA). bFGF detected on
      the cell surface and within the cells could be partially removed by treatment
      with heparin or heparinase and with heparin or DNase, respectively. Exogenous
      bFGF bound to cells not producing bFGF was also quantified by ISARA. Measurements
      of bFGF in extracts of cells producing bFGF suggested that 8.3-13.3% of the bFGF
      associated with the cells was detected by ISARA. This method should be useful for
      quantitative confirmation of immunohistochemical results on bFGF.

PMID- 7513266
TI  - [Hepatitis C antibodies in health personnel].
AB  - Using the second generation test, the authors examined 320 health professionals
      of the Faculty Hospital in Plzen and dialyzation centres in Karlovy Vary and
      Sokolov for the presence of antibodies against the hepatitis C virus. Antibodies
      were detected in 7 of them (2.2%). Serum positivity was confirmed only in
      paramedical workers, the highest herd immunity was recorded in workers in the
      dialyzation centre in Plzen. The authors evaluate the prevalence of antibodies in
      relation to age and period of practice in the health services.

PMID- 7513267
TI  - [Studies of two conjugates of monoclonal antibody (HIM6) and cytosine
      arabinoside].
AB  - Two conjugates (HIM6-PAD-ara C and HIM6-PLGA-ara C) of the anticancer agent
      cytosine arabinoside (ara C) and monoclonal antibody (HIM6) against human
      leukocytes were prepared with dextran T-40 and poly-L-glutamic acid as
      intermediate carriers, respectively. The drug-antibody conjugates maintained most
      of the original antigen-binding activity of the free antibody. The ratio of
      positive bound cells was found to be > 90% by an indirect immunofluorescence
      assay. The cytotoxicities of HIM6-PAD-ara C and HIM6-PLGA-ara C against antibody
      reactive human leukemia HL60 cells were lower than those of free ara C and a
      mixture of ara C and HIM6 (IC50s of HIM6-PAD-ara C, HIM6-PLGA-ara C, ara C and
      the mixture of ara C and HIM6 were 0.212, 0.102, 0.028 and 0.024 microgram/ml,
      respectively), but were similar to those of the intermediates PAD-ara C and PLGA
      ara C. On the other hand, these two conjugates showed no cytotoxic its against
      non-target hepatoma cells. These results indicate that the specific cytotoxicity
      of the conjugate depends on specific binding to the target surface antigen by the
      monoclonal antibody in the conjugate molecule.

PMID- 7513268
TI  - [Effects of 764-3 on the organization and function of microtubules and
      microfilaments in bleomycin A6 activated rat alveolar macrophages].
AB  - Using bleomycin A6 (BLM A6) to stimulate normal and 764-3 pretreated alveolar
      macrophages (AM) in vitro, the distributions of microtubules (MTs) and
      microfilaments (MFs) were examined with an immunofluorescence microscope.
      Fluorescent strength was determined with a spectrophotometer and
      fluorospectrophotometer, and the adhering and spreading rates were determined.
      The results showed that BLM A6-stimulated AM spread fully and MTs increased
      markedly, forming a thick network in the cytoplasm. Much punctate and linear
      fluorescence was visible beneath the plasma membrane, these fluorescing
      structures were MFs. In the experimental cells MT and MF fluorescence was
      stronger than that in the control group. However, most of the above changes were
      reduced in the 764-3 pretreatment group. These results suggest that BLM A6 may
      promote the assembly and regulate reorganization of MTs and MFs, while 764-3 can
      stabilize these structures.

PMID- 7513269
TI  - [The study of intermediate filament organization of highly and poorly
      differentiated nasopharyngeal carcinoma cell lines].
AB  - By employing cytochemistry, immunocytochemistry, selective double extraction,
      whole mount electron microscopy and electrophoretic scanning quantitative
      analysis, the intermediate filaments (IF) of in vitro cultured nasopharyngeal
      carcinoma cell lines CNE-1 (highly differentiated) and CNE-2Z (poorly
      differentiated) have been studied. The results demonstrated that although the
      keratin-type IF were organized in a network pattern in both kinds of cells,
      significant differences could be observed between the two kinds of cells
      regarding IF organization, subtypes and quantity of keratin. The poorly
      differentiated cell line CNE-2Z exhibited a far more irregular and confused IF
      organization structure, and the content of keratin was lower while the variety of
      keratin subtypes was increased.

PMID- 7513270
TI  - Antiarrhythmic drug classifications and the clinician: a gambit in the land of
      chaos.
AB  - Several classifications of antiarrhythmic drugs have appeared and all suffer
      considerable limitations. Recently a Task Force of the Working Group on
      Arrhythmias of the European Society of Cardiology proposed a novel classification
      of antiarrhythmic drugs (the so-called Sicilian Gambit) based on their action on
      the most vulnerable parameter of an arrhythmogenic mechanism. The present article
      attempts a critical reappraisal of the antiarrhythmic drug actions and the
      relationship of vulnerable parameters with cellular mechanisms such as ion
      channels. The clinical applicability of these concepts, the implications of the
      new classification in the pharmacologic therapy of arrhythmias, and its potential
      limitations are discussed.

PMID- 7513271
TI  - Role of apical ion channels in sour taste transduction.
AB  - Sour taste perception depends primarily on the concentration of H+ in the taste
      stimulus. Acid stimuli elicit concentration-dependent action potentials in taste
      cells. Recent patch-clamp studies suggest that protons depolarize taste cells by
      direct interaction with apically located ion channels. In Necturus maculosus, the
      voltage-dependent K+ conductance is restricted to the apical membrane of taste
      cells. The current flows through a variety of K+ channels with unitary
      conductances ranging from 30 to 175 pS, all of which are blocked directly by
      citric acid applied to outside-out or perfused cell-attached patches. In
      contrast, hamster fungiform taste cells appear to utilize the amiloride-sensitive
      Na+ channel for acid transduction. Amiloride completely inhibits H+ currents
      elicited by acid stimuli in isolated taste cells, with an inhibition constant
      similar to that for amiloride-sensitive Na+ currents (Ki = 0.2 microM). Treatment
      of isolated taste cells with the bioactive peptide arginine-vasopressin results
      in similar increases in both the amiloride-sensitive Na+ and H+ currents; the
      effect is mimicked by 8-bromocyclic AMP. These results suggest that H+ can
      permeate amiloride-sensitive Na+ channels in hamster fungiform taste cells,
      contributing to the transduction of sour stimuli.

PMID- 7513272
TI  - Ion pathways in the taste bud and their significance for transduction.
AB  - Taste buds share a topology with ion-transporting epithelial and evidence now
      indicates that neural responses in rats to Na+ salts of differing anion are
      mediated by both transcellular and paracellular ion transport. Na+ exerts its
      effects mainly on the transcellular pathway. Neural responses to Na+ salts are
      enhanced by negative voltage clamp and suppressed by positive clamp in a manner
      indicating modulation of the apical membrane potential of receptor cells. Anion
      effects are mainly paracellular. Under zero current clamp increasing anion size
      reduces the neural response at constant Na+ concentration. Below about 50 mM this
      difference is entirely eliminated under voltage clamp. This suggests that
      paracellular transepithelial potentials normally create an anion difference. At
      higher concentrations the relatively high permeability of the paracellular shunt
      to Cl- permits sufficient electroneutral diffusion of NaCl below the tight
      junctions to stimulate cells that do not make direct contact with the oral
      cavity. In general, the sensitivity of a response to perturbations in the apical
      membrane potential indicates that some phase of Na+ salt taste transduction is
      accompanied by changes in an apical membrane channel conductance.

PMID- 7513273
TI  - [An immunohistochemical study of retinoblastoma].
AB  - Various immunohistochemical marders were detected in 27 specimens of human
      retinoblastoma by the avidin-biotin-peroxidase complex technique, using mono- and
      polyclonal antibodies. The glial markers, glial fibrillary acidic protein and Leu
      7 were detected in the retinal tissue component and reactive perivascular glial
      cells in the tumor mass. In only 4 of the 27 specimens, Leu-7 was positive in the
      glial cells randomly interspersed among the tumor cells and not associated with
      blood vessels. The neuronal marker, neuron-specific enolase, stained strongly
      positive in undifferentiated tumor cells in most (21/27) of the specimens.
      Rhodopsin, the photoreceptor marker which exists only in the outer segments of
      photoreceptor cells, was detected in the fleurettes of 1 tumor and in the
      rosettes of 6 tumors, these results support the view that retinoblastoma is
      chiefly neuronal in nature with tendency to differentiate into photoreceptor
      cells and rarely into glial cells.

PMID- 7513276
TI  - Chronic hepatitis C.
AB  - Formerly the diagnosis of acute and chronic non-A, non-B hepatitis was made by
      the exclusion of other causes. However, in 1989 cloning of an antigenic component
      of the hepatitis C virus (HCV) was reported. This led to first- and second
      generation tests for antibody to HCV (anti-HCV) in serum. HCV has been associated
      with acute and chronic posttransfusion and sporadic non-A, non-B hepatitis, and
      with hepatocellular carcinoma. Viral HCV RNA can be estimated with the polymerase
      chain reaction test, but this technically difficult test is not generally
      available. The entire viral genome has been sequenced. The envelope region shows
      considerable variation, and mutant HCV infections are being described already.
      There are geographic variations in the prevalence of anti-HCV, but usually about
      0.5% to 1% of healthy blood donors test positive. Parenteral exposure to blood,
      especially by transfusion or drug abuse, remains a certain means of acquiring HCV
      infection. The method by which millions without parenteral risk factors acquire
      HCV remains uncertain. Vertical transmission and sexual and family spread occur
      only rarely. Body secretions are free of the virus. The mode of transmission may
      become clarified when tests for viral HCV as opposed to anti-HCV become generally
      available. Acute HCV infection usually is mild, and the chronic disease is also
      indolent. Carriers of hepatitis B virus or alcoholics who also test positive for
      HCV have more serious disease. Chronic HCV infection must be distinguished from
      autoimmune chronic active hepatitis. The most important difference is the
      response to corticosteroid therapy, which is good in autoimmune hepatitis and
      poor in HCV-related disease. Hepatocellular carcinoma can complicate HCV-related
      cirrhosis, usually about 20 years after infection with HCV. Recombinant
      interferon-alpha is used to treat chronic HCV disease, but selection of patients,
      dose, and duration of therapy are uncertain. In general, 50% of patients respond
      to the treatment, but 50% of these will have a relapse, with an overall response
      rate of 25%. Liver transplantation in patients with end-stage HCV disease usually
      is followed by infection of the graft.

PMID- 7513275
TI  - Distribution of nitric oxide synthase containing neurons in the rectal myenteric
      plexus and anal canal. Morphologic evidence that nitric oxide mediates the
      rectoanal inhibitory reflex.
AB  - PURPOSE: Following the demonstration that a novel neurotransmitter, nitric oxide
      (NO), is released during neurogenic relaxation of the internal anal sphincter in
      vitro, it has been suggested that NO could mediate the rectoanal inhibitory
      reflex in vivo. The aim of this study was to establish whether the distribution
      of NO-producing nerves in the anorectum is consistent with this proposed role.
      METHODS: NO is synthesized in neurons which contain the enzyme nitric oxide
      synthase and their presence in the anorectum was determined in tissue obtained
      from nine abdominoperineal and three anterior resection specimens in patients
      undergoing surgery for rectal carcinoma. Cryostat sections were stained for
      nitric oxide synthase immunoreactivity, pan-neuronal/axonal immunoreactivity, and
      NADPH diaphorase activity. RESULTS: Nitric oxide synthase immunoreactivity is
      present in a subpopulation of neurons in rectal myenteric ganglia which also
      contain NADPH diaphorase activity. Use of the latter histochemical technique
      enabled the structure and distribution of nitric oxide synthase containing
      neurons to be determined in whole-mount preparations. Individual neurons have
      Dogiel type 1 morphology and are present throughout the rectal myenteric plexus.
      In the distal rectum, positively stained axons enter shunt fascicles which
      descend into the anal canal, where they ramify into and throughout the internal
      anal sphincter. Within the sphincter, positively stained nerves lie in close
      proximity to smooth muscle cells. CONCLUSION: These results are consistent with
      the hypothesis that NO is the neurotransmitter that mediates the rectoanal
      inhibitory reflex.

PMID- 7513274
TI  - TOTO and YOYO: new very bright fluorochromes for DNA content analyses by flow
      cytometry.
AB  - Flow cytometric (FCM) studies were performed on nuclei, ethanol-fixed CHO cells,
      and isolated human GM130 chromosomes stained with two new cyanine dyes, TOTO and
      YOYO. These fluorochromes, which are dimers of thiazole orange and oxazole
      yellow, respectively, have high quantum efficiencies and exhibit specificities
      for both DNA and RNA. Bound to dsDNA in solution, TOTO and YOYO emit at 530 and
      510 nm, respectively, when excited at 488 nm and 457 nm, wavelengths available
      from most lasers employed in FCM. RNase-treated CHO nuclei, stained with either
      TOTO or YOYO, provided DNA histograms, with low coefficients of variation, that
      were as good as or better than those obtained with nuclei stained with propidium
      iodide (PI) or mithramycin (MI). In addition, by comparison on an equimolar
      basis, nuclei stained with YOYO fluoresced over 1,000 times more intensely than
      nuclei stained with MI. Fluorescence ratio analyses of nuclei stained with both
      YOYO and Hoechst 33258 showed that the ratio of YOYO to Hoechst fluorescence
      remained relatively constant for G1 and S phase cells, but decreased
      significantly for cells in G2/M. These results indicate that the cyanine dyes may
      be useful in examining specific changes in chromatin structure during G2/M phases
      of the cell cycle. Ethanol-fixed CHO cells stained with TOTO or YOYO did not
      yield reproducible DNA histograms of good quality, presumably because of the poor
      accessibility of DNA to these large fluorochromes. However, bivariate analyses of
      human GM130 chromosomes stained with TOTO or YOYO alone and excited sequentially
      with uv and visible wave-lengths showed resolution of many individual chromosome
      peaks similar to results obtained for chromosomes stained with HO and chromomycin
      A3. Collectively, these studies show potential advantages for the use of these
      new cyanine dyes in FCM studies that require the sensitive detection of DNA.

PMID- 7513277
TI  - [Acute pancreatitis due to the rupture of an echinococcal cyst into the bile duct
      system].
AB  - A 47-year-old woman with stones in the gall-bladder suddenly developed severe
      upper abdominal pain. Cholesterol concentration was elevated, as were amylase
      (555 U/l) and lipase (408 U/l) concentrations, suggesting biliary pancreatitis.
      Endoscopic retrograde cholangiography demonstrated a cyst, about 10 cm in
      diameter, in the left lobe of the liver, connected to the biliary tract system.
      Ultrasonography and computed tomography additionally showed a smaller cyst in the
      right lobe. Infection with Echinococcus granulosus was proven microbiologically
      on bile (demonstration of hooklets and protoscolices) as well as serologically.
      Transpapillary cholangioscopy demonstrated daughter cysts within the echinococcal
      cyst. The main cyst was rinsed with 20% NaCl for 10 days via a nasocystic
      catheter. In addition, mebendazole (three times daily 1000 mg) was administered
      for 13 months. The signs if inflammation receded and the cyst shrank to a small
      residual volume. Surgical intervention became unnecessary.

PMID- 7513278
TI  - Spatiotemporal expression of SCIP and myelin genes in rat brain during early
      postnatal development.
AB  - The expression of the SCIP and myelin genes (PLP, BP and MAG) was quantitated by
      Northern blot analysis during early postnatal rat brain development. The SCIP
      gene was already profoundly upregulated on day 1 postpartum. The SCIP message
      level in the forebrain was 4- and 17-fold higher than the message level in the
      cerebellum and brainstem, respectively. By day 20, the SCIP gene expression
      declined in the forebrain to approximately 5% of the day-1 level, and became
      undetectable in the brainstem and cerebellum. The myelin gene expression sharply
      upregulated at approximately day 7-8, and in general, was highest in the
      brainstem, and lowest in the forebrain. The results demonstrate that the
      expression of the SCIP gene in the oligodendrocytic lineage cells is relatively
      low, whereas other cellular elements feature very active expression of the gene
      during the early postnatal development. Additionally, the variation in the
      relative ratios of the myelin messages among the brain regions indicates that the
      levels of expression of the myelin genes are not tightly synchronized.

PMID- 7513279
TI  - Accelerated myelinogenesis induced by dietary lipids in rats.
AB  - Our previous work has shown an early development of behavioral reflexes in the
      offspring of rats maintained on diets containing a lipid fraction extracted from
      yeast (Candida lypolitica) grown on n-alkanes during pregnancy and throughout
      lactation. Since some of these changes could be linked to an early myelination,
      in this study we investigated myelin maturation in the rat brain by
      immunohistochemistry. At 7 days the test groups showed considerable
      immunopositivity to myelin basic protein and proteolipid protein at a more
      rostral level, such as the corpus callosum where immunopositivity is usually
      detected later in brain development. At 7 days in controls, staining fibers were
      detected only in the lower brainstem and in the cerebellum. Immunopositivity in
      the same regions was more intense in the test groups. Some litters were fostered
      at birth to produce 2 groups of animals: pups whose mothers were fed a control
      diet prenatally and the test diet postnatally, and vice versa. Positive fibers
      are already present at 7 days in the telencephalon area in both groups. These
      data indicate that dietary lipids can interfere with brain development by
      accelerating myelinogenesis.

PMID- 7513280
TI  - Follicle-stimulating hormone (FSH) receptors and FSH-responsive adenosine 3',5'
      cyclic monophosphate production in porcine granulosa cells decline with
      follicular growth.
AB  - Comparison of binding of 125I-porcine FSH to porcine granulosa cells from small
      and large ovarian follicles indicated that binding is dependent on both time and
      temperature. At 37 C, binding of ligand is more than four times higher in cells
      from small follicles than in cells from large follicles within 30 minutes of the
      start of incubation. Binding to cells from both small and large follicles is more
      stable for a longer period of time at 20 C than at 37 C. Equilibrium saturation
      binding analysis of 125I-pFSH binding indicated that binding is saturable and of
      high affinity. Granulosa cells from small and large follicles have similar
      affinities for 125I-pFSH. However, granulosa cells from small follicles have 4.7
      times as many FSH receptors as granulosa cells from large follicles. The
      sensitivity and responsiveness of the adenylyl cyclase system to FSH were
      assessed by incubating cells from small and large follicles with increasing
      concentrations of FSH in a defined medium containing isobutylmethylxanthine (1
      mM), an inhibitor of phosphodiesterase. Granulosa cells from small follicles are
      more sensitive to FSH and have a greater cAMP response to FSH than granulosa
      cells from large follicles. Thus, both active FSH receptors and FSH-responsive
      adenylyl cyclase activity decline during follicular growth.

PMID- 7513281
TI  - Isolation and characterization of an olive allergen-like protein from lilac
      pollen. Sequence analysis of three cDNA encoding protein isoforms.
AB  - An olive allergen-like protein has been isolated from lilac (Syringa vulgaris)
      pollen extract. The protein can be considered as an allergen since is recognized
      by IgE from olive hypersensitive human sera, and has been called Syr v I (IUIS
      nomenclature). This protein consists of a glycosylated polypeptide of 20 kDa,
      which has an amino acid composition, spectroscopic properties, and an N-terminal
      sequence similar to the major allergen from olive pollen, Ole e I. The lilac
      allergen is recognized by rabbit polyclonal antisera raised against olive
      allergen as well as by an Ole e I-specific monoclonal antibody. Using a
      polymerase chain reaction strategy, based on the similarities observed between
      these olive and lilac proteins, three cDNA clones encoding Syr v I have been
      isolated and sequenced. These clones code for a polymorphic protein of 145
      residues with a derived molecular mass of about 16,400Da, which contains a
      potential N-glycosylation site. Comparison of the deduced amino acid sequences of
      these Syr v I isoforms to each other revealed identities of 90-97%. Moreover,
      these sequences showed a high degree of similarity (85.5-89.6% identity) with Ole
      e I. The structural and immunological characterization of Syr v I justify the
      cross-reactions observed between olive and lilac pollen extracts. The molecular
      cloning of Syr v I is relevant for the epitope mapping in Oleaceae allergens, and
      may contribute to an improvement in the design of reagents for diagnosis and
      therapy of IgE-dependent allergic reactions.

PMID- 7513283
TI  - The protective role of high-density lipoprotein on oxidized-low-density
      lipoprotein-induced U937/endothelial cell interactions.
AB  - The adherence of monocytes to the endothelium is an early event in atherogenesis.
      We have investigated this process by examining whether native and oxidized low
      density and high-density lipoproteins could modulate this process. Only oxidized
      low-density lipoprotein caused a significant dose-dependent and time-dependent
      increase in U937 monocyte-like cell line binding to human endothelial cells, by a
      process which required de novo protein synthesis. Interestingly, E-selectin,
      intercellular adhesion molecule-1, vascular cell-adhesion molecule or P-selectin
      induction was not apparent in this system suggesting the presence of an
      alternative system for the interaction of endothelial cells with monocyte-like
      cells in response to oxidized low-density lipoprotein. High-density lipoprotein
      completely suppressed oxidized low-density-lipoprotein-induced adhesion of U937
      cells to the endothelial monolayer, while oxidized high-density lipoprotein did
      not. These data suggest that the balance between native and oxidized lipoproteins
      may play a role in the formation of the atherosclerotic lesion by modulating
      monocyte endothelial interactions.

PMID- 7513284
TI  - RNA editing in trypanosomes.
AB  - The nucleotide sequence of mitochondrial pre-mRNAs in trypanosomes is
      posttranscriptionally edited by the insertion and deletion of uridylate (U)
      residues. In some RNAs editing is limited to small sections but in African
      trypanosomes, such as Trypanosoma brucei, 9 of the 18 known mitochondrial mRNAs
      are created by massive editing which can produce more than 50% of the coding
      sequence. In all cases, however, RNA editing is a key event in gene expression
      during which translatable RNAs are generated. The information for the editing
      process and possibly also the inserted Us are provided by small guide RNAs, which
      are encoded in both the maxicircle and minicircle components of the trypanosome
      mitochondrial DNA. Current models of editing are largely based on the
      characteristics of partially edited RNAs and on the occurrence in vivo and the
      possibility of synthesis in vitro of chimeric molecules in which a guide RNA is
      covalently linked through its 3' oligo(U) tail to an editing site in pre-mRNA. In
      this paper, I will review the research in this rapidly growing field and
      illustrate how different interpretations of the available data can lead to
      different views of the mechanism and the biochemistry of the editing process.

PMID- 7513282
TI  - Caffeine-induced calcium oscillations in heavy-sarcoplasmic-reticulum vesicles
      from rabbit skeletal muscle.
AB  - Heavy-sarcoplasmic-reticulum vesicles from rabbit skeletal muscle show not only
      caffeine-induced calcium release in a medium allowing active calcium loading, but
      also oscillations in calcium concentration under appropriate conditions. The
      xanthine derivatives 7-isobutyl-1-methylxanthine and theophylline also induce
      oscillations under the same conditions. Calcium-releasing substances with other
      chemical structures such as adenosine nucleotides or calmodulin antagonists do
      not induce this effect. With the help of specific inhibitors such as ruthenium
      red, neomycin or magnesium it was demonstrated that the oscillation mechanism
      involves the ryanodine receptor/calcium channel. When ATP was substituted by GTP
      or ITP no oscillations occurred after caffeine application. The subsequent
      application of ATP, but not of adenosine 5'-[gamma-thio]triphosphate or adenosine
      5'-[beta,gamma-methylene]triphosphate activated the oscillating mechanism,
      showing ATP to be an essential component of the oscillating system. We
      investigated the influence of the experimental conditions by altering the
      caffeine and ATP concentrations, calcium load, pH and ionic strength amongst
      other parameters. Potassium and anion channels are not involved in calcium
      oscillations of heavy sarcoplasmic reticulum, nor are the oscillations dependent
      on membrane potential.

PMID- 7513285
TI  - MRI of Joubert's syndrome.
AB  - OBJECTIVE: To report five cases of the rare Joubert's syndrome. SUBJECTS: All
      five cases were studied by 1.0-Tesla MRI. All the patients showed typical
      clinical manifestations of Joubert's syndrome including neonatal respiratory
      abnormalities, developmental delay, ataxia, retinal atrophy and nystagmus.
      RESULTS: The T1WI of MRI showed characteristic MRI features of Joubert's syndrome
      including dilatation of the fourth ventricle with some appearing bat-wing shaped,
      elongation and stretching of the superior cerebellar peduncles, dysphasia of the
      vermis, widening of the foramen of Magendie and the posterior cistern. One case
      was associated with encephalomeningocele. CONCLUSIONS: MRI can provide
      characteristic findings of Joubert's syndrome and confirm the clinical diagnosis.

PMID- 7513286
TI  - A two-domain model for the R domain of the cystic fibrosis transmembrane
      conductance regulator based on sequence similarities.
AB  - CFTR belongs to a group of proteins sharing the structural motif of six
      transmembrane helices and a nucleotide binding domain. Unique to CFTR is the R
      domain, a charged cytoplasmic domain. Comparison of R domain sequences from ten
      species revealed that the N-terminal third is highly conserved, while the C
      terminal two-thirds is poorly conserved. The R domain shows no strong sequence
      similarity to known proteins; however, 14 viral pol proteins show limited
      similarity to fragments of the R domain. Analysis revealed a relationship between
      the N- and C-terminal fragments of the R domain and two discontinuous fragments
      of the pol protein. These observations support a two-domain model for the R
      domain.

PMID- 7513287
TI  - Human immunodeficiency virus type 1 (HIV-1) recombinant reverse transcriptase.
      Asymmetry in p66 subunits of the p66/p66 homodimer.
AB  - A recombinant p66 form of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) can be obtained [(1991) Biotechnol. Appl. Biochem. 14, 69-81]
      from crude Escherichia coli extracts by immobilized metal affinity chromatography
      (IMAC). We have analyzed the p66 HIV-1 RT, isolated in the presence of 0.3 M
      imidazole, by gel permeation HPLC on Superose 12. The results show that it
      contains two major distinct p66 forms (24.1 min and 28.3 min peaks) which are
      distinguishable from the purified homodimeric (p66/p66) HIV-1 RT (22.2 min peak).
      Protein peak 1 (24.1 min) is converted to a 22.3 min peak upon storage for 20 h
      at 4 degrees C. Under identical conditions, the isolated peak 2 (28.3 min)
      appeared as a conformationally heterogeneous mixture elaborated by peaks at 22.3
      min and 25.9 min. The protein species thus obtained were active in the RNA
      dependent DNA polymerase and RNase H activity assays and produced heterodimeric
      HIV-1 RT upon incubation with the HIV-1 protease. When the IMAC-purified,
      imidazole-free homodimeric (p66/p66) form of the enzyme was incubated with 0.3 M
      imidazole for 16 h at 4 degrees C, protein peaks at 28.3 min (peak A) and 30.5
      min (peak B) were isolated by gel permeation HPLC. While both of these p66
      containing species were stable and displayed identical RNA-dependent DNA
      polymerase activities, the protein in peak B was only 50% active in RNase H
      function compared with the protein from peak A. These imidazole-mediated
      dissociation studies support the hypothesis of partial unfolding of one of the
      RNase H domains of the p66/p66 homodimer, suggesting that the p66 subunits are
      asymmetric in the native enzyme.

PMID- 7513288
TI  - Immunophilins in protein folding and immunosuppression.
AB  - Lymphocyte activation requires the transmission of signals from molecules at the
      plasma membrane to nuclear signals that regulate gene expression. In recent
      years, several immunosuppressive compounds have been used as probes to identify
      important and potentially novel molecules involved in lymphocyte signal
      transduction processes. The immunosuppressants cyclosporin A (CsA), FK506, and
      rapamycin have been studied in particular detail. Two distinct classes of
      immunosuppressant binding proteins have been identified, and collectively termed
      immunophilins. The cyclophilin family of immunophilins binds CsA, whereas the
      FK506-binding protein (FKBP) family binds FK506 and rapamycin. This review will
      discuss both the endogenous functions of immunophilins as well as their roles in
      mediating immunosuppression.

PMID- 7513289
TI  - Angiogenesis and colonization in the tumor metastatic process: basic and applied
      advances.
AB  - Tumor metastasis is a major cause of death for cancer patients. This review
      proposes that the final steps in the development of a distant metastasis may be
      the most productive targets for clinical development. It cannot be guaranteed
      that, in "metastasis-free" patients, tumor cells have not invaded out of the
      primary lesion, intravasated and extravasated from the circulatory system, and
      are sitting at distant sites as occult micrometastases. The remaining processes
      involved in outgrowth at metastatic sites, colonization and angiogenesis, are
      reviewed. Colonization is thought to be accomplished by clonally dominant cell
      populations through progressive independence from exogenous growth factors,
      production of growth factors, and stimulatory proliferative responses to
      traditionally inhibitory cytokines. Therapeutic efforts aimed at interrupting the
      switch in tumor cell responsiveness to cytokines, rather than to any one specific
      cytokine, may be most successful at inhibiting metastatic colonization.
      Angiogenesis has been demonstrated to be directly or indirectly induced by a
      plethora of cytokines. Partial suppression of neovascularization can be achieved
      in tissue culture and animal models using various natural and pharmaceutical
      angiostatic agents. However, as with clonal dominance, such agents must be able
      to suppress the redundant effects of angiogenesis-promoting factors. This review
      discusses the current literature on colonization and angiogenesis, emphasizing
      its underlying mechanisms and potential therapeutic applications.

PMID- 7513290
TI  - [Study of the combined effect of hexachlorane and mercury depending on their
      content in the body].

PMID- 7513291
TI  - Heterogeneity in the severity of cystic fibrosis and the role of CFTR gene
      mutations.
AB  - Cystic fibrosis is a common, fatal disorder caused by abnormalities in the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encodes a chloride
      channel that regulates secretion in many exocrine tissues. The presentation of
      cystic fibrosis is highly variable as measured by the age of onset of disease,
      the presence of pancreatic insufficiency, or the progression of lung disease.
      Over 400 mutations in the CFTR gene have been described in cystic fibrosis
      patients and considerable effort has focused on the correlation between specific
      mutations and genotypes and clinical characteristics. Individual tissues display
      variation in their sensitivity to CFTR mutations. The vas deferens is
      functionally disrupted in nearly all males, whereas mild and severe pancreatic
      involvement is determined by the patient's genotype. The severity of pulmonary
      disease is poorly correlated with genotype, suggesting that there are other
      important genetic and/or environmental factors that contribute to lung infections
      and the subsequent disruption of lung function.

PMID- 7513292
TI  - Retrospective study of the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene mutations in Guthrie cards from a large cohort of neonatal screening
      for cystic fibrosis.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a
      cAMP-activated chloride channel, and in individuals with both alleles of the gene
      mutated, symptoms of CF disease are manifest. With more than 300 mutations so far
      described in the gene the profile of mutant alleles in a population is specific
      to its ethnic origin. For an analysis with an unbiased recruitment of the CF
      alleles in neonates of similar origin (Normandy, France), we have retrospectively
      analyzed the Guthrie cards of affected newborns, diagnosed by the immunoreactive
      trypsinogen (IRT) assay. Analysis of the 27 exons of the CFTR gene using a GC
      clamp denaturing gradient gel electrophoresis (DGGE) assay has enabled us to
      identify over 96% of the mutated alleles. Two of these were novel mutations. We
      would like to propose this strategy as an efficient method of retrospective
      molecular genetic diagnosis that can be performed wherever Guthrie cards can be
      obtained. Knowledge of rare alleles could be a prerequisite for CF therapy in the
      future.

PMID- 7513293
TI  - Analysis of the CFTR gene confirms the high genetic heterogeneity of the Spanish
      population: 43 mutations account for only 78% of CF chromosomes.
AB  - We have analysed 972 unrelated Spanish cystic fibrosis patients for 70 known
      mutations. Analysis was performed on exons 1, 2, 3, 4, 5, 6a, 6b, 7, 10, 11, 12,
      13, 14a, 14b, 15, 16, 17b, 18, 19, 20 and 21 of the cystic fibrosis transmembrane
      regulator gene using single strand conformation polymorphism analysis and
      denaturing gradient gel electrophoresis. The major mutation delta F508 accounts
      for 50.6% of CF chromosomes, whereas another 42 mutations account for 27.6% of CF
      chromosomes, with 21.8% of Spanish CF chromosomes remaining uncharacterized. At
      present, we have identified 36 mutations that have frequency of less than 1% and
      that are spread over 15 different exons. This indicates that, in the Spanish
      population, with the exception of delta F508 (50.6%) and G542X (8%), the
      mutations are not concentrated in a few exons of the gene nor are there any
      predominating mutations. This high degree of genetic heterogeneity is mainly a
      result of the different ethnic groups that have populated Spain and of the
      maintenance of separated population sets (Basques, Arab-Andalusian,
      Mediterranean, Canarian and Gallician). The high proportion of CF chromosomes
      still unidentified (21.8%) together with association analysis with intragenic
      markers suggest that at least 100 different mutations causing CF are present in
      our population.

PMID- 7513294
TI  - Analysis of the whole CFTR coding regions and splice junctions in azoospermic men
      with congenital bilateral aplasia of epididymis or vas deferens.
AB  - Several recent studies have demonstrated the presence of mutations in the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene in healthy males with
      infertility caused by congenital absence of the vas deferens (CBAVD), previously
      recognized as an idiopathic genetic condition distinct from CF. In order to
      document further the genetic commonality of these two disorders, we undertook a
      double screening of the entire coding and flanking sequences of the CFTR gene, by
      using single-strand conformational polymorphism analysis and denaturing gradient
      gel electrophoresis in 12 unrelated infertile men with abnormalities of the vas
      deferens and/or epididymis. This strategy allowed us to identify 11 DNA sequence
      alterations considered as CF-causing mutations and several variations. Despite
      this double analysis, only two patients out of eight with CBAVD could be
      demonstrated as compound heterozygotes for CF mutations.

PMID- 7513295
TI  - Absence of FMR-1 gene expression can be detected with RNA extracted from dried
      blood specimens.
AB  - Fragile X syndrome is a genetic disorder caused by abnormal function of the FMR-1
      gene. The majority of fragile X syndrome patients carry an expansion of the CGG
      tri-nucleotide repeat in the FMR-1 gene, whereas others have a deletion or a
      point mutation in the FMR-1 structural gene. In this report, we analyzed a
      typical family with three male patients. RNA from Epstein-Barr virus transformed
      lymphoblastoid cells was used for RNase protection assay and reverse
      transcription-polymerase chain reaction (RT-PCR) analysis. Five normal
      individuals and one asymptomatic heterozygote from this family expressed
      detectable FMR-1 transcripts, whereas three fragile X patients showed no sign of
      expression with either assay. To extend the application of this PCR-based assay
      to laboratory diagnosis of fragile X syndrome, we confirmed that dried blood
      samples collected on screening filter papers for newborns are an adequate source
      of RNA for RT-PCR. Moreover, fragile X patients from the study family and another
      family were reliably identified by the absence of the FMR-1-specific PCR product
      from the dried blood specimens. Our studies indicate that this simple assay can
      be used to diagnose the fragile X syndrome for the majority of male patients.

PMID- 7513296
TI  - Novel cystic fibrosis mutation associated with mild disease in Cypriot patients.
AB  - Cyprus is an island in the eastern Mediterranean basin inhabited by people of
      Caucasian extraction, mostly Greek-Cypriots. The most common inherited disease
      among Caucasians is cystic fibrosis (CF). Although no careful scientific study
      had ever been done the impression was that CF was extremely rare among the Greek
      Cypriots, with an incidence estimated at around 1:30,000. About 2 years ago, we
      introduced molecular diagnostic methodology in an effort to assist clinicians in
      safer diagnosis of patients presenting with atypical CF symptomatology, and also
      for testing the hypothesis that mutations that cause milder phenotypes might be
      responsible for misdiagnosis or for missing entirely some cases of CF. Initial
      screening for delta F508 revealed that it is indeed rare in the general
      population. Further screening of suspected CF patients revealed a novel mutation
      that converted leucine at position 346 to proline (L346P) in two unrelated
      families. The second CF mutation was delta F508 and 1677delTA in the two families
      respectively, both reportedly associated with severe phenotypes. Yet our patients
      did not present with typical CF pictures possibly because of the dominant nature
      of this novel mild mutation in exon 7. Symptoms included failure to thrive, chest
      infections and electrolyte disturbances. These findings raise the possibility
      that Cyprus might have been spared very severe CF phenotypes but not cystic
      fibrosis transmembrane conductance regulator (CFTR) mutations.

PMID- 7513297
TI  - CD19 maps to a region of conservation between human chromosome 16 and mouse
      chromosome 7.
AB  - CD19 is a B lymphocyte cell surface protein expressed from the earliest stages of
      B lymphocyte development until their terminal differentiation into plasma cells.
      In this report the human CD19 gene (hCD19) was localized to band p11.2 on the
      proximal short arm of chromosome 16 by in situ hybridization to metaphase
      chromosomes, using hCD19 cDNA as probe. hCD19 gene localization was confirmed by
      polymerase chain reaction based analysis with hCD19-specific primers, using a
      panel of human/hamster somatic cell hybrid DNA as templates. The mouse CD19 gene
      (mCd19) was mapped to bands F3-F4 of chromosome 7 by in situ hybridization to
      metaphase chromosomes, using a mCD19 cDNA probe. Segregation analysis of
      nucleotide sequence polymorphisms in interspecific backcross progeny revealed
      linkage of mCd19 with hemoglobin beta (Hbb), Int-2, and H19, other loci
      previously mapped to the same region of mouse chromosome 7, confirming the
      localization of mCd19 to this region. The order of these loci was determined to
      be centromere--Hbb--mCd19--H19--Int-2--telomere. The genetic distances between
      the loci examined, calculated from the recombination frequencies, suggested that
      mCd19 was located centrally between Hbb and H19. This region of mouse chromosome
      7 is homologous to the region of human chromosome 16 to which the hCD19 gene
      maps. Multiple genes with a lymphocyte-related function also map to this
      conserved region including genes encoding the IL-4 receptor, CD11a, CD11b, CD11c,
      CD43 (leukosialin), and protein kinase C beta polypeptide.

PMID- 7513298
TI  - Cold storage of peripheral nerves: an in vitro assay of cell viability and
      function.
AB  - The development of a nerve bank as a source of donor material to repair large
      defects in peripheral nerve injuries requires an understanding of the influence
      of cold storage on cell viability and function in these potential nerve grafts.
      Segments of peripheral nerves from both human and rat were stored in University
      of Wisconsin Cold Storage Solution (UW) at 4 degrees C for < 12 h, 3 days, and 1,
      2, or 3 weeks. Cellular viability was initially assessed by the degree of
      cellular outgrowth from explants of the stored nerves placed in culture, and then
      further quantitated by dissociating the cultured nerve explants and calculating
      the type and number of cells per milligram of peripheral nerve. Rat Schwann cells
      (SCs) obtained from the stored (control and 1 and 2 weeks) nerves were tested for
      their functional ability to myelinate dorsal root ganglion (DRG) neurons in
      culture. Our findings indicate that human and rat peripheral nerves contain few
      viable SCs and fibroblasts after 3 weeks of cold storage with the quantity of
      viable cells within the human cold stored peripheral nerves decreasing
      significantly after 1 week of cold storage. Despite their reduced number, some
      SCs from rat nerves stored up to 2 weeks are capable of myelinating DRG axons in
      culture. These results suggest that short intervals (< 1 week) of cold storage
      will result in potential peripheral nerve grafts containing large populations of
      functional cells, while long-term (> or = 3 weeks) cold stored peripheral nerves
      will contain few viable cells.

PMID- 7513299
TI  - The slippery slope of health care reform.

PMID- 7513300
TI  - CD14 and CD11b mediate serum-independent binding to human monocytes of an
      acylpolygalactoside isolated from Klebsiella pneumoniae.
AB  - A water-soluble acylpolygalactosyl (APG) of 34 kDa was obtained from the
      Klebsiella pneumoniae membrane by alkaline hydrolysis and delipidation. APG
      comprises a poly(1,3)galactose chain, a core, and a lipid moiety made of a
      glucosamine disaccharide with two N-linked beta OH-myristates. The monocyte
      binding sites for APG were investigated by flow cytometry. Biotin-labelled APG
      (Biot-APG) bound to monocytes at 4 degrees C in the absence of serum, calcium,
      and magnesium. The binding was dose dependent, saturable, and displaced by
      unlabelled APG. Neither the polysaccharide chain present in APG-related molecules
      nor the PPi group or additional ester-linked myristates and palmitates were
      required for APG binding. The role of CD11b and CD14 was demonstrated by
      competitive inhibition with monoclonal antibodies and by the uptake of APG by
      these solubilized proteins. APG was rapidly internalized into monocytes at 37
      degrees C while CD14 and CD11b/CD18 molecules were partially down-modulated.
      Lipopolysaccharides (LPS) from the same K. pneumoniae strain and from Escherichia
      coli and Salmonella minnesota partially competed for Biot-APG binding in the
      absence but not in the presence of serum. When altered by alkaline hydrolysis,
      those LPS became strong competitors for APG binding. It was concluded that
      alkaline hydrolysis of the K. pneumoniae membrane yielded molecules structurally
      related to LPS which bind to LPS membrane receptors in the absence of serum.

PMID- 7513302
TI  - Meningococcal group A lipooligosaccharides (LOS): preliminary structural studies
      and characterization of serotype-associated and conserved LOS epitopes.
AB  - Structural studies indicate that the neisserial lipooligosaccharides (LOS) are
      composed of an oligosaccharide (OS) portion with a phosphorylated diheptose (Hep)
      core attached to the toxic lipid A moiety. A conserved meningococcal LOS epitope,
      defined by monoclonal antibody (MAb) D6A, is expressed on group A and many group
      B and C meningococci of different LOS serotypes (J. J. Kim, R. E. Mandrell, H.
      Zhen, M. A. Apicella, J. T. Poolman, and J. M. Griffiss, Infect. Immun. 56:2631
      2638, 1988). This MAb-defined D6A epitope is immunogenic in humans (M. M.
      Estabrook, R. E. Mandrell, M. A. Apicella, and J. M. Griffiss, Infect. Immun.
      58:2204-2213, 1990; M. M. Estabrook, C. J. Baker, and J. M. Griffiss, J. Infect.
      Dis. 197:966-970, 1993). In this study, we characterize this important MAb
      defined LOS epitope. Serotype L10 and L11 group A meningococal LOS were
      chemically modified and used to investigate what portion of the LOS molecule is
      important for expression of the conserved (D6A) epitope and serotype-associated
      LOS epitopes by use of immunoblotting techniques and selected MAbs as probes.
      Preliminary structural characterization of the LOS was also accomplished by
      electrospray ionization-mass spectrometry. Our results indicate the following.
      (i) Antibodies that recognize the serotype-associated or conserved LOS epitopes
      recognize the OS portion of the LOS. (ii) The phosphorylated diheptose core
      region of the OS is essential for expression of the conserved D6A epitope. (iii)
      The lipid portion of the molecule is important for optimum expression of the LOS
      epitopes. (iv) The proposed compositions of the O-deacylated LOS are consistent
      with the presence of a phosphorylated diheptose core and are as follows: for O
      deacylated L10 LOS, 3Hex (hexose), 1HexNAc (N-acetylhexosamine), 2KDO (2-keto-3
      deoxy-D-manno-octulosonic acid), 2Hep (heptose), 1PEA or 2PEA
      (phosphoethanolamine), and O-deacylated lipid A; and for O-deacylated L11 LOS,
      2Hex, 1HexNAc, 2KDO, 2Hep, 2PEA, and O-deacylated lipid A. Because the
      phosphorylated diheptose core region of the LOS is essential for the formation of
      a conserved LOS epitope (D6A) that is immunogenic in humans, care should be taken
      to maintain stereochemical requirements for the expression of this conserved
      epitope in the design of effective, nontoxic LOS vaccines.

PMID- 7513303
TI  - Antibody recognition of a neutralization epitope on the major outer membrane
      protein of Chlamydia trachomatis.
AB  - Two BALB/c mice were immunized with serovar C Chlamydia trachomatis elementary
      bodies, and 63 hybridomas producing monoclonal antibodies to C. trachomatis were
      recovered. Eight hybridomas which were specific for an identical peptide epitope
      (AGLQND) in serovar C major outer membrane protein variable domain I were
      identified. Detailed immunochemical study of the antigen-antibody interaction and
      genetic characterization of the antibody variable-region gene sequences showed
      that distinct B-cell clonal lineages were elicited by the epitope sequence. Since
      each antibody had a distinct pattern of fine specificity for recognition of the
      epitope and displayed different degrees of cross-reactivity with a related
      serovar (serovar A), we conclude that B-cell recognition of an immunodominant
      neutralization epitope can be pleiotropic. Differences in B-cell recognition of a
      neutralization epitope may delay the emergence by mutation of antigenic-drift
      variants of the C. trachomatis major outer membrane protein.

PMID- 7513301
TI  - Tumor necrosis factor alpha augments nitric oxide-dependent macrophage
      cytotoxicity against Entamoeba histolytica by enhanced expression of the nitric
      oxide synthase gene.
AB  - Nitric oxide (NO measured as nitrite, NO2-) is the major effector molecule
      produced by activated macrophages for in vitro cytotoxicity against Entamoeba
      histolytica trophozoites. In this study, we determine whether tumor necrosis
      factor alpha (TNF-alpha) produced by activated bone marrow-derived macrophages
      (BMM) is involved in the induction of the inducible NO synthase gene (mac-NOS)
      for NO-dependent amebicidal activity. TNF-alpha alone did not directly induce
      macrophage NO2- production to kill amebae; however, in combination with
      increasing concentrations of TNF-alpha and gamma interferon (IFN-gamma), BMM
      amebicidal activity and NO2- production progressively increased and showed a
      significant linear correlation. Antiserum to TNF-alpha and the NO synthase
      inhibitor NG-monomethyl L-arginine (L-NMMA) inhibited the synergistic effects of
      TNF-alpha and IFN-gamma. BMM activated with increasing concentrations of
      lipopolysaccharide (LPS) and IFN-gamma showed a significant linear correlation
      between TNF-alpha release and NO2- production. Antiserum to TNF-alpha suppressed
      TNF-alpha release, NO2- production, and amebicidal activity by 93, 53, and 86%,
      respectively. L-NMMA diminished NO2- production by 74% and macrophage amebicidal
      activity by 83% but had no effect on TNF-alpha release. Quantification by
      Northern (RNA) blot analyses demonstrated that IFN-gamma in combination with TNF
      alpha or LPS increased markedly the accumulation of mac-NOS and TNF-alpha mRNAs
      in a time-dependent manner with a concomitant increase in NO and TNF-alpha
      production. Peak induction of mac-NOS occurred after 24 h, whereas TNF-alpha mRNA
      was rapidly expressed after 4 h and remained stable for 48 h. Taken together,
      these data argue that TNF-alpha augments NO-dependent macrophage cytotoxicity
      against E. histolytica via elevated levels of mac-NOS mRNA expression which may
      be associated with the accumulation of TNF-alpha mRNA.

PMID- 7513305
TI  - Evolution of CD4 T-cell subsets following infection of naive and memory immune
      mice with Mycobacterium tuberculosis.
AB  - We report here that during the course of an experimental infection of mice with
      Mycobacterium tuberculosis, the differential expression of the cell surface
      antigens CD44 and CD45RB could be used to delineate CD4+ T cells into four
      phenotypically distinct subsets. The major subset present was designated
      CD44lo/CD45RBhi and is associated with naive or resting T cells. The three
      remaining subsets expressed increased levels of the CD44 antigen as the infection
      progressed and could therefore be considered to be in an activated state. These
      activated populations could be further divided on the basis of their variable
      expression of the CD45RB antigen. These populations were designated
      CD44hi/CD45RBhi, CD44hi/CD45RBlo, and CD44hi/CD45RBneg. Kinetic studies of the
      emergence of these populations indicated that these subsets arose sequentially
      from the naive population at times associated with the peak expression of
      acquired specific resistance. In further studies, in an attempt to associate
      either the CD44hi/CD45RBlo or the CD44hi/CD45RBneg population with acquired
      immunologic memory of tuberculosis infection, draining lymph nodes of challenged
      memory immune animals were analyzed for the accumulation of the CD4+ subsets. The
      accumulation of both the CD44hi/CD45RBlo and the CD44hi/CD45RBneg populations was
      observed, but the CD44hi/CD45RBlo population was enriched in a manner consistent
      with the rapid accumulation of memory T cells during the anamnestic response.
      While functional roles for each of these subsets remain to be determined, these
      data provide the first evidence for the evolution of multiple, phenotypically
      distinct CD4+ T-cell subsets during the in vivo response to an experimental
      mycobacterial infection.

PMID- 7513304
TI  - Antigens shared by Leishmania species and Trypanosoma cruzi: immunological
      comparison of the acidic ribosomal P0 proteins.
AB  - Patients with visceral leishmaniasis produce high levels of immunoglobulin, but
      the specificities of antibodies produced are not well characterized. In an effort
      to identify leishmania antigens that are specific to Leishmania species or are
      cross-reactive with other parasitic protozoa, we have cloned and characterized
      full-length genomic and cDNA clones encoding a Leishmania chagasi acidic
      ribosomal antigen, LcP0, recognized during human infections. The protein is
      homologous to the Trypanosoma cruzi and human ribosomal proteins TcP0 and HuP0,
      respectively. Unlike most higher eukaryotes, but similar to TcP0, LcP0 has a C
      terminal heptapeptide sequence resembling those of the archaebacterial acidic (P
      like) proteins. The highly charged C-terminal acidic domain of LcP0 contains a
      serine residue typically found in most eukaryotes but lacking in all T. cruzi P
      proteins we have characterized thus far. L. chagasi-infected individuals as well
      as those with T. cruzi infections have antibodies cross-reactive with recombinant
      LcP0 and TcP0 as well as HuP0. However, the properties of anti-P0 antibodies in
      T. cruzi and L. chagasi infection sera are quite different. Through the use of
      synthetic peptides, we showed that while T. cruzi infection anti-TcP0 antibodies
      are exclusively directed against the C-terminal domain of TcP0, L. chagasi
      infection sera contain antibodies reactive with epitopes other than the C
      terminal sequence of LcP0. Thus, anti-LcP0 antibodies in L. chagasi infection
      sera represent the first characterized deviation from the restricted
      immunodominant C-terminal epitope involved in the generation of anti-P0
      antibodies following infection or autoimmune diseases.

PMID- 7513307
TI  - Formaldehyde treatment of proteins can constrain presentation to T cells by
      limiting antigen processing.
AB  - Proteins to be used as vaccines are frequently treated with formaldehyde,
      although little is known about the effects of this treatment on protein
      antigenicity. To investigate the effect of formaldehyde treatment on antigen
      recognition by T cells, we compared the in vitro T-cell response to proteins that
      have been formaldehyde treated with the response to untreated proteins. We found
      that peripheral blood mononuclear cells from individuals vaccinated with three
      formaldehyde-treated proteins (pertussis toxin, filamentous hemagglutinin,
      pertactin) of Bordetella pertussis showed little or no response to the
      formaldehyde-treated proteins but proliferated very well in response to the
      corresponding untreated protein. These findings were further confirmed with CD4+
      T-cell clones specific for defined epitopes of the bacterial proteins. We found
      that some epitopes are presented poorly or not at all when formaldehyde-treated
      proteins are used, whereas other epitopes are equally presented to T-cell clones
      when either formaldehyde-treated or untreated antigens are used. However, T-cell
      recognition could be restored by either antigen degradation before formaldehyde
      treatment or heat denaturation after such treatment. Parallel digestion with
      trypsin of both formaldehyde-treated and untreated proteins showed that fragments
      generated from the two forms of the same antigen were different in size. These
      results demonstrate that formaldehyde treatment can constrain antigen
      presentation to T cells and that this may be due to an altered proteolytic
      processing of formaldehyde-treated proteins.

PMID- 7513306
TI  - Cell-mediated responses of immunized vervet monkeys to defined Leishmania T-cell
      epitopes.
AB  - A population of vervet monkeys was immunized with killed parasites and infected
      with Leishmania major promastigotes either by needle or by infected-fly bite. The
      responses of recovered monkeys to mitogens, killed parasites, and molecularly
      defined T-cell epitopes were then compared with those of control animals.
      Peripheral blood mononuclear cells (PBMC) from both naive and recovered animals
      proliferated strongly in response to both B- and T-cell mitogens, although the
      responses of the recovered animals were less strong than those of the naive
      animals. Cells from recovered vervets, but not those from naive vervets, also
      proliferated in response to parasite antigens and synthetic T-cell epitopes.
      Likewise, cells from recovered animals released gamma interferon and either
      interleukin 2 (IL-2) or IL-4 into culture media in response to both of the above
      mentioned antigens, whereas cells from control animals did not. The fact that no
      IL-5 could be measured following parasite antigen or synthetic T-cell epitope
      stimulation of PBMC suggested that cells proliferating in response to these
      molecules belonged to the Th1 subset. Phenotypic analysis of the PBMC showed a
      marked increase in T-cell but not B-cell populations in recovered animals. Among
      this population was an increased number of CD45R0+ memory cells. The data from
      this study are in keeping with the earlier finding that vervet monkeys provide an
      excellent model system for leishmaniasis. Further, these data support the
      contention that synthetic T-cell epitopes are prime candidates for molecularly
      defined Leishmania vaccines.

PMID- 7513308
TI  - Isolation and characterization of Pseudomonas pseudomallei flagellin proteins.
AB  - Flagellin proteins from several different strains of Pseudomonas pseudomallei
      have been isolated and purified to homogeneity by mechanical shearing and
      differential centrifugation techniques. Analysis by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis yielded flagellin monomer protein bands with
      an estimated M(r) of 43,400. No lipopolysaccharide contamination of the purified
      protein preparations was detectable by silver staining of flagellin displayed on
      polyacrylamide gels and by Western immunoblotting with P. pseudomallei
      antilipopolysaccharide monoclonal antibody. NH2-terminal amino acid sequence
      analysis of the flagellin protein of P. pseudomallei 319a revealed significant
      homology with flagellins from Proteus mirabilis, Bordetella bronchiseptica, and
      Pseudomonas aeruginosa PAK. Rabbit polyclonal antiserum raised against the 319a
      flagellin protein reacted with 64 of 65 P. pseudomallei strains tested. The
      polyclonal antiserum proved effective in inhibiting the motility of these
      organisms in motility agar plates. Passive immunization studies demonstrated that
      319a flagellin-specific antiserum was capable of protecting diabetic rats from
      challenge with a heterologous P. pseudomallei strain.

PMID- 7513309
TI  - A bactericidal antibody to Borrelia burgdorferi is directed against a variable
      region of the OspB protein.
AB  - Borrelia burgdorferi, an agent of Lyme disease, is killed by some monoclonal
      antibodies in the absence of complement or phagocytes. In the present study, the
      bactericidal action of monoclonal antibodies against B. burgdorferi and B.
      hermsii, a cause of relapsing fever, was further characterized. H6831, an
      antibody recognizing the OspB proteins of some B. burgdorferi strains, and H4825,
      an antibody specific for one serotype of B. hermsii, were purified, and Fab
      fragments of the antibodies were prepared. In time-kill studies, more than 99.9%
      of strain B31 B. burgdorferi cells were killed after 30 min of exposure to H6831
      Fab fragments. The MBC of the Fab fragments was 10 micrograms/ml. Electron
      microscopy revealed that the bactericidal Fab fragments produced numerous blebs
      and cell lysis of the borrelias for which they were specific. To identify the
      epitope for H6831, the OspB sequences of H6831-susceptible and -resistant strains
      and mutants were determined. The deduced OspB proteins of all H6831-resistant
      strains and mutants differed from the strain B31 OspB at residue 253. Murine
      antisera raised against a 21-mer synthetic peptide representing the region around
      residue 253 were specific for strain B31 by Western blot (immunoblot) and growth
      inhibition assays. Furthermore, the antipeptide serum inhibited the binding of
      H6831 to whole borrelias. These findings indicated that the linear component of
      the bactericidal antibody's epitope was located at or near residue 253.

PMID- 7513310
TI  - Characterization of a linear epitope on Chlamydia trachomatis serovar L2 DnaK
      like protein.
AB  - A cytoplasmic 75-kDa immunogen from Chlamydia trachomatis serovar L2 has
      previously been characterized as being similar to the Escherichia coli heat shock
      protein DnaK. We have localized a linear epitope for one monoclonal antibody
      specific for C. trachomatis DnaK. By use of a recombinant DNA technique, the
      epitope was limited to 14 amino acids. With synthetic peptides, the epitope was
      further limited to eight amino acids. Six of these amino acids are conserved in
      bovine HSP70, which has a known three-dimensional structure. The amino acid
      sequence homologous to the epitope is located in a linear part of the HSP70
      molecule known as connect II.

PMID- 7513311
TI  - Cloning and B-cell-epitope mapping of MPT64 from Mycobacterium tuberculosis
      H37Rv.
AB  - The gene of the immunogenic protein MPT64 found in culture filtrates of
      Mycobacterium tuberculosis H37Rv was cloned and sequenced. A comparison showed
      mpt64 and the gene encoding MPB64 from Mycobacterium bovis BCG Tokyo to be
      identical except for one silent mutation. The regions encoding the promoter and
      the signal peptide were also well conserved for the two sequences. Southern blot
      experiments on genomic mycobacterial DNA showed the presence of mpt64 in the M.
      tuberculosis substrains H37Rv, H37Ra, and Erdman and in the M. bovis BCG
      substrains Tokyo, Moreau, and Russian, whereas the M. bovis BCG substrains Glaxo,
      Pasteur, Canadian, Tice, and Danish 1331 and Mycobacterium leprae lack the gene.
      Southern blot analyses revealed differences in the restriction enzyme patterns
      within the M. tuberculosis substrains as well as within the M. bovis BCG
      substrains, indicating either different chromosomal localization of mpt64 or that
      mutations have occurred at different locations on the chromosomes. N-terminal and
      C-terminal deletion mutants were constructed for the mapping of B-cell epitopes
      on MPT64 with five monoclonal antibodies, C24b1, C24b2, C24b3, L24b4, and L24b5.
      Western blot (immunoblot) analysis revealed that the murine antibodies bind to
      one linear and three conformational epitopes.

PMID- 7513313
TI  - Penner's serotype 4 of Campylobacter jejuni has a lipopolysaccharide that bears a
      GM1 ganglioside epitope as well as one that bears a GD1 a epitope.
AB  - The carbohydrate structures of lipopolysaccharides (LPSs) of Campylobacter jejuni
      strains belonging to Penner's serotypes (PEN) 1, 2, 4, 19, 23, and 36 were
      studied by thin-layer chromatography and immunostaining with several monoclonal
      antiganglioside antibodies. Anti-GM1 and anti-GD1a antibodies reacted with the
      LPSs of PEN 1, 4, and 19. Aspinall et al. (G. O. Aspinall, A. G. McDonald, T. S.
      Raju, H. Pang, A. P. Moran, and J. L. Penner. Eur. J. Biochem. 213:1017-1027,
      1993) recently reported that the LPS of PEN 4 has a GD1a ganglioside-like
      structure rather than a GM1-like structure. We found that the LPS fraction of C.
      jejuni (PEN 4) has an LPS that bears a GM1 epitope as well as an LPS that bears a
      GD1a epitope.

PMID- 7513314
TI  - Immunolocalization of granulocyte-colony-stimulating factor in human glial and
      primitive neuroectodermal tumors.
AB  - Granulocyte-colony-stimulating factor (G-CSF) is a hematopoietic cytokine that
      regulates the differentiation of myeloid progenitors and the function of mature
      neutrophils. It is produced in vitro by monocytes/macrophages, mesothelial cells,
      fibroblasts and endothelial cells after appropriate induction by inflammatory
      mediators like IL-1 and TNF. Normal as well as tumorous glial cells can also be
      induced to produce CSFs in vitro. However, little is yet known about the in vivo
      expression of G-CSF as a mediator in inflammation and malignancy within the human
      central nervous system. The aim of the present study was to investigate by
      immunostaining the expression of the G-CSF protein within non-tumorous and
      tumorous glial tissues, and primitive neuroectodermal tumors. Using the murine
      monoclonal anti-G-CSF TM 82/60 antibody, we found high G-CSF expression in
      astrocytoma WHO grades I and II and reactive brain tissue, low expression in
      astrocytoma WHO grade III, and none in glioblastoma, oligodendroglioma WHO grades
      II and III, and medulloblastoma. In consecutive sections of the tissue samples, G
      CSF protein was localized in GFAP-positive glial cells, but not in
      macrophages/microglial cells, which expressed HLA-DR, detected by the antibody
      CR3/43. Computer-assisted microdensitometric evaluation of the intensity of
      immunostaining for G-CSF and statistic analysis of the data revealed significant
      differences between the diagnostic entities studied (p < 0.0001). We conclude
      that in vivo expression of G-CSF is a characteristic of reactive as well as
      tumorous astrocytes, with the latter losing this feature at higher degrees of
      dedifferentiation.

PMID- 7513312
TI  - Effect of growth factors on Escherichia coli alpha-hemolysin-induced mediator
      release from human inflammatory cells: involvement of the signal transduction
      pathway.
AB  - Previously, we have shown that Escherichia coli alpha-hemolysin represents a
      potent stimulus for inflammatory mediator release (O2- release, beta
      glucuronidase release, and leukotriene generation) from human polymorphonuclear
      granulocytes (PMN) as well as for histamine release from a human lymphocyte
      monocyte-basophil cell suspension (LMB). In contrast, the E. coli alpha-hemolysin
      leads to a downregulation of cytokine release (interleukin 6 [IL-6], tumor
      necrosis factor alpha, and IL-1 beta) from human LMB. This study was undertaken
      (i) to analyze the priming efficacy of growth factors (granulocyte-macrophage
      colony-stimulating factor [GM-CSF] and granulocyte CSF [G-CSF]) on inflammatory
      mediator release from human PMN and LMB challenged with hemolysin-producing E.
      coli bacteria as well as with cell-free E. coli alpha-hemolysin and (ii) to
      identify major components involved in GM-CSF and G-CSF priming. GM-CSF
      pretreatment led to an increased chemiluminescence response from human PMN by up
      to 100%, leukotriene B4 generation was enhanced up to fivefold, and histamine
      release from human LMB increased from 45% +/- 15% to 75% +/- 5% (mean +/-
      standard distribution) of the total histamine content. G-CSF priming induced an
      increase in the chemiluminescence response by up to 50% +/- 5% from human PMN and
      an increase in histamine release from human LMB by 20% +/- 5%. The growth
      factors, GM-CSF and G-CSF, modulated neither beta-glucuronidase release from
      human PMN nor IL-8 release from human PMN and LMB challenged with the E. coli
      alpha-hemolysin. GM-CSF and G-CSF pretreatment increased the fluoride (NaF)
      induced chemiluminescence response by up to 10-fold; the serine/threonine
      phosphatase inhibitor okadaic acid inhibited GM-CSF- and G-CSF-induced priming.
      NaF-induced histamine release was enhanced up to 60 and 30% by GM-CSF and G-CSF
      priming, respectively. GM-CSF and G-CSF pretreatment did not modulate phorbol 12
      myristate 13-acetate-induced chemiluminescence response or histamine release. GM
      CSF by itself induced an increase in 5-lipoxygenase-specific mRNA expression
      within 5 min. Our results indicate that (i) GM-CSF and G-CSF interact with
      inflammatory cells via distinct cellular signalling, (ii) the signal transduction
      pathway is dependent on the cellular mediator, and (iii) the use of growth
      factors may be a potent tool to influence the clinical outcome in infectious
      diseases.

PMID- 7513315
TI  - Acroangiodermatitis: a study of ten cases.
AB  - BACKGROUND: Acroangiodermatitis is a benign vesicular process encountered on the
      lower extremities that histologically resembles the superficial form of stasis
      dermatitis, but is clinically characterized by circumscribed violaceous, brown or
      dusky macules, papules, or plaques. Furthermore, unlike stasis dermatitis,
      acroangiodermatitis is usually associated with minimal epidermal changes and
      eosinophils in the inflammatory infiltrate in the dermis. Kaposi's sarcoma,
      pigmented purpura, vasculitis, and lichen planus are other conditions that should
      be considered when making a diagnosis of acroangiodermatitis. METHODS: Ten
      patients with acroangiodermatitis were referred to us by area physicians.
      Hematoxylin and eosin, periodic acid-Schiff, Pearl's (an iron stain), and an
      immunoperoxidase stain for Factor VIII were performed on routinely embedded
      paraffin sections. RESULTS: All cases showed new vessel proliferation,
      perivascular inflammation of superficial and mid-dermis, consisting of
      lymphocytes, histiocytes, eosinophils, occasional plasma cells, extravasation of
      red blood cells, and hemosiderin pigment deposition. Dermal fibrosis was observed
      in all cases. None of the patients showed changes of vasculitis or Kaposi's
      sarcoma. Only one patient displayed significant epidermal changes of spongiosis
      and mild acanthosis. CONCLUSIONS: Acroangiodermatitis is an uncommon entity with
      peculiar clinical and histologic features and should be confirmed by histologic
      tests.

PMID- 7513316
TI  - Phenotype analysis of unstimulated lymphocytes and anti-CD3-stimulated
      proliferating T-cells from cerebrospinal fluid and peripheral blood in patients
      with multiple sclerosis and other neurological diseases.
AB  - In 15 patients with multiple sclerosis (MS) and in 11 patients with other
      neurological diseases (OND), the phenotype of fresh unstimulated CSF and PB
      mononuclear cells and of "in vitro" expanded T-cells was studied by monoclonal
      antibody stain and cytofluorimeter analysis. A compartment-specific decrease of
      CD8+Leu8+ and CD8+Leu8- cells in CSF was detected; moreover, lower levels of
      CD8+Leu8- cells were seen in MS than in OND patients, both in CSF and in PB.
      Although the percentages of unstimulated CSF CD4+ cells did not differ between MS
      and OND, a higher proportion of "in vitro" expanded CD4+ T-cells was obtained
      from MS patients than from OND. Among MS patients, T-cell growth was very scarce
      or absent in those sampled during relapses. The results suggest alterations both
      within the CD4+ "helper" and the CD8+ "suppressor-cytotoxic" populations in the
      CSF of MS patients, and stress the relevance of functional analysis in
      conjunction with phenotype studies.

PMID- 7513317
TI  - Therapeutic alternatives to surgery for benign prostatic hyperplasia. Scientific
      foundations and techniques.

PMID- 7513320
TI  - The use of 33P-labelled riboprobes for in situ hybridizations: localization of
      myosin alkali light-chain mRNAs in adult human skeletal muscle.
AB  - 33P-labelled probes were used to localize the mRNAs coding for the myosin alkali
      light-chain isoforms MLC 1f/3f and MLC 1sb in adult human muscles, which are
      distributed in characteristic fibre type specific patterns. In situ
      hybridizations of 33P-labelled probes were compared with probes carrying 35S or
      digoxigenin labels. Signals of equal strength were obtained with each of the
      three labels. The preferentially peripheral localization of these mRNAs in the
      muscle fibres could be clearly seen with all three probes, with digoxigenin
      probes providing the best resolution. 33P can serve as a viable alternative in
      this type of experiment. These experiments with adult human muscles also showed
      that the post mortem stability of RNA in human muscle is better than generally
      assumed. We could detect no signs of degradation in RNA prepared from heart
      ventricle as well as skeletal muscle up to 24 hours post mortem. In situ
      hybridizations worked equally well in biopsy material as in post mortem samples.

PMID- 7513319
TI  - Developmental changes in the expression of the liver-enriched transcription
      factors LF-B1, C/EBP, DBP and LAP/LIP in relation to the expression of albumin,
      alpha-fetoprotein, carbamoylphosphate synthase and lactase mRNA.
AB  - Expression of alpha-fetoprotein, carbamoylphosphate synthase and albumin, that
      are generally accepted markers for the hepatic phenotype, require a distinct set
      of transcription factors. We investigated by in situ hybridization whether this
      set of transcription factors, LF-B1, C/EBP, DBP and LAP/LIP, is expressed
      coordinately in the liver during embryonic development and to what extent they
      are also expressed elsewhere. Our results demonstrate that mRNA levels of all
      transcription factors tested are significantly above background in the whole
      embryo and are either reduced or enhanced in expression during subsequent
      development. Interestingly, cardiac mesoderm, which induces prehepatic endoderm
      to liver formation, is temporarily permissive to its own signals, showing
      enhanced expression of these transcription factors and, as a result, the
      hepatocyte-specific genes alpha-fetoprotein and carbamoylphosphate synthase. In
      addition, these transcription factors and many liver-specific structural genes
      rise concomitantly in intestine and kidney just before birth, suggesting the
      expression of hepatogenic factors in these tissues as well. Despite the
      extrahepatic expression of these transcription factors, expression of albumin
      remains confined to the liver at all developmental stages.

PMID- 7513322
TI  - Localization of cytokeratin 4 mRNA in human oesophageal epithelium by non
      radioactive in situ hybridization.
AB  - An RNA probe complementary to human cytokeratin 4 mRNA was produced by in vitro
      transcription, and labelled with digoxigenin-UTP. Using this probe, an in situ
      hybridization protocol was established, tested and optimized for the localization
      of the cytokeratin 4 mRNA in formalin- or paraformaldehyde-fixed, paraffin
      embedded human oesophageal mucosa. The hybridization signal was exclusively
      detected in the cytoplasm of epithelial cells as coarse brown granules. The
      positive signal always showed a consistent and distinct pattern throughout the
      epithelium, starting from the third to fourth layer of epithelial cells, and
      reaching into the superficial cell layers, but was never found in the basal cell
      layer, the suprabasal layers, and the upper adluminal strata. Some intermediate
      cell layers of the epithelium lining the upper part of the secretory duct of
      submucosal glands were also positive. Similar results could also be obtained in
      sections from routinely fixed, paraffin-embedded tissue samples. The described
      signal pattern was found at all levels of the oesophagus. The signal distribution
      was in agreement with previous biochemical and immunohistochemical studies on the
      spreading of the cytokeratin 4 protein throughout the oesophageal epithelium. We
      may conclude that also the expression of the gene(s) encoding cytokeratin 4 in
      the human oesophageal epithelium depends on the vertical cell differentiation and
      the detachment from the basal lamina. The developed simplified but sensitive in
      situ hybridization method may be a useful tool in routine histology,
      physiopathology, clinical research, and clinical diagnosis, concerning normal
      oesophageal epithelium structure and differentiation, and development of
      oesophageal malignancies.

PMID- 7513321
TI  - Secretory and absorptive activity of oesophageal epithelium: evidence of
      circulating mucosubstances.
AB  - The space between the oesophageal basal and prickle epithelial cells appears
      empty by standard ultrastructural preparative techniques. Fixation of human
      oesophageal biopsies with a variety of agents, including tannic acid,
      glutaraldehyde-lysine, cetylpyridinium chloride and Ruthenium Red shows that this
      space is filled with mucosubstances, some free, some attached to the cells as a
      glycocalyx. There is evidence that this material is secreted constitutively by
      the basal and prickle cells. This secretion may be changed or blocked by
      incubating oesophageal biopsies in the presence of colchicine or dinitrophenol.
      Incubation at 16 degrees C has the same effect. Absorption from the intercellular
      space may be followed using the fluid phase marker, horseradish peroxidase. Early
      endosomes may also be shown by their acid phosphatase activity. Incubation of
      biopsies at 20-22 degrees C allows early endosomes to accumulate material, but
      not pass it on the late endosomes.

PMID- 7513318
TI  - A user's guide for avoiding errors in absorbance image cytometry: a review with
      original experimental observations.
AB  - The sources of errors which may occur when cytophotometric analysis is performed
      with video microscopy using a charged-coupled device (CCD) camera and image
      analysis are reviewed. The importance of these errors in practice has been
      tested, and ways of minimizing or avoiding them are described. Many of these
      sources of error are known from scanning and integrating cytophotometry; they
      include the use of white instead of monochromatic light, the distribution error,
      glare, diffraction, shading distortion, and inadequate depth of field. Sources of
      errors specifically linked with video microscopy or image analysis are
      highlighted as well; these errors include blooming, limited dynamic range of grey
      levels, non-linear responses of the camera, contrast transfer, photon noise, dark
      current, read-out noise, fixed scene noise and spatial calibration. Glare,
      contrast transfer, fixed scene noise, depth of field and spatial calibration seem
      to be the most serious sources of errors when measurements are not carried out
      correctly. We include a table summarizing all the errors discussed in this review
      and procedures for avoiding them. It can be concluded that if accurate
      calibration steps are performed and proper guidelines followed, image cytometry
      can be applied safely for quantifying amounts of chromophore per cell or per unit
      volume of tissue in sections, even when relatively simple and inexpensive
      instrumentation is being used.

PMID- 7513323
TI  - The cell blot assay in analysis of rat anterior pituitary cell secretion.
AB  - We have investigated the efficacy of the cell blot assay in analysis of the
      secretion of hormones and peptides from rat anterior pituitary cells. The
      dissociated cells are cultured on pieces of translucent polyvinylidene difluoride
      membrane, on which their secretory products are adsorbed and subsequently
      immunostained. The area and integrated optical density of the stained 'halo'
      surrounding individual cells is measured by microscopical image processing and
      the values for basal secretion of a particular hormone or peptide are compared
      with those after application of secretagogues or inhibitors. Our experiments
      tested established responses of dissociated rat anterior pituitary cells; in
      general, the results were as expected. Double immunoenzymatic staining could be
      used to show secretion of two products from the same or different cells in one
      preparation, and immunofluorescence with fluorescein- and/or rhodamine-labelled
      antibodies could be used instead of enzyme-linked immunolabelling. Optimal
      dilutions of immunoreagents were much higher than those used for
      immunocytochemistry on tissue sections. Although the cell blot assay does not
      provide absolute quantification, since some of the secreted product escapes into
      the medium, it is a relatively easy and economical way for morphologists to
      compare secretion from individual cells under varying conditions.

PMID- 7513327
TI  - Cutaneous malacoplakia.
AB  - Indurated, erythematous plaques of the left arm and left flank developed in a 69
      year-old white man with multiorgan failure from Escherichia coli sepsis.
      Cutaneous malacoplakia was diagnosed. Intravenous antibiotic therapy resulted in
      resolution of the malacoplakia and the E. coli sepsis.

PMID- 7513324
TI  - Reactive attachment disorder of infancy or early childhood.
AB  - Since its introduction into DSM-III, reactive attachment disorder has stood
      curiously apart from other diagnoses for two reasons; it remains the only
      diagnosis designed for infants, and it requires the presence of a specific
      etiology. This paper describes the pattern of disturbances demonstrated by some
      children who meet DSM-III-R criteria for reactive attachment disorder. Three
      suggestions are made: (1) the sensitivity and specificity of the diagnostic
      concept may be enhanced by including criteria detailing the developmental
      problems exhibited by these children; (2) the etiological requirement should be
      discarded given the difficulties inherent in obtaining complete histories for
      these children, as well as its inconsistency with ICD-10; and (3) the diagnosis
      arguably is not a disorder of attachment but rather a syndrome of atypical
      development.

PMID- 7513325
TI  - Effect of 4.5S RNA depletion on Escherichia coli protein synthesis and secretion.
AB  - We examined the synthesis of individual proteins following depletion of 4.5S RNA
      by using a strain deficient in the induction of heat shock proteins. We found
      that initially the synthesis of all proteins was equally affected, and the
      peptide elongation rate was reduced by approximately 10%. For up to 1 generation
      time after the onset of inhibition of total protein synthesis, the processing of
      secreted proteins was unaffected. After further depletion of 4.5S RNA,
      accumulation of precursors of secreted proteins was observed under some growth
      conditions.

PMID- 7513326
TI  - Mechanism of binding of the antisense and target RNAs involved in the regulation
      of IncB plasmid replication.
AB  - The replication frequency of the IncB miniplasmid pMU720 is dependent upon the
      expression of the repA gene. Binding of a small, highly structured, antisense RNA
      (RNA I) to its complementary target in the RepA mRNA (RNA II) inhibits repA
      expression and thus regulates replication. Analyses of binding of RNA I to RNA II
      indicated that the reaction consists of three major steps. The first step,
      initial kissing complex formation, involves base pairing between complementary
      sequences in the hairpin loops of RNA I and RNA II. The second step is
      facilitated by interior loop structures in the upper stems of RNA I and RNA II
      and involves intrastand melting and interstrand pairing of the upper stem regions
      to form an extended kissing complex. This complex was shown to be sufficient for
      inhibition of repA expression. The third step involves stabilization of the
      extended kissing complex by pairing between complementary single-stranded tail
      regions of RNA I and RNA II. Thus, the final product of RNA I-RNA II binding is
      not a full duplex between the two molecules.

PMID- 7513328
TI  - Borderline tuberculoid Hansen's disease in AIDS.
AB  - We performed an immunohistochemical analysis of a skin lesion from a patient with
      AIDS who had borderline tuberculoid Hansen's disease. We also evaluated other
      laboratory features and performed peripheral blood flow cytometric analysis. The
      in situ immunologic response to Mycobacterium leprae was minimally affected by
      concomitant infection and immunosuppression by HIV. The skin demonstrated the
      typical characteristics of borderline tuberculoid lesions. These results indicate
      that although a patient with HIV infection may have laboratory evidence typical
      of the immunosuppression seen in AIDS, the immunologic response to M. leprae is
      essentially unchanged.

PMID- 7513331
TI  - Biochemical changes in the coxal organ proper and accessory glands of female
      Ornithodoros (Ornithodoros) savignyi at different physiological conditions.
AB  - Changes in the total protein, DNA, RNA, lipid and phospholipid concentrations in
      the coxal organ proper and accessory glands of Ornithodoros (Ornithodoros)
      savignyi (Audouin) were studied. There was an increase in the total protein, DNA,
      RNA, lipid and phospholipid content of the coxal organ proper in the female upto
      6-days after feeding, then the concentration decreased. Also, the content of
      protein, DNA, RNA, lipid and phospholipid in the coxal organ proper of the
      seventh nymphal instar were similar to unfed females. Accessory glands showed an
      increase in protein, DNA, RNA, lipid and phospholipid content that reached its
      maximum on day 8 after feeding in females, then decreased.

PMID- 7513332
TI  - Symptom control in terminally ill patients with malignant bowel obstruction
      (MBO).
AB  - The inadequacy of prolonged conservative management with nasogastric suction and
      intravenous fluids for terminally ill patients with bowel obstruction has long
      been recognized. Using previous reports and our experience on the Palliative Care
      Unit at the Edmonton General Hospital, we have developed a basic approach to
      bowel obstruction management. In a review of 100 consecutive patients who died on
      our Palliative Care Unit, 15 required medical management for bowel obstruction.
      Evaluation of these cases suggests that intensive medical management can provide
      good symptom control without using intravenous lines and with minimal use of
      nasogastric tubes.

PMID- 7513330
TI  - Borrelia burgdorferi and Escherichia coli lipopolysaccharides induce nitric oxide
      and interleukin-6 production in cultured rat brain cells.
AB  - Borrelia burgdorferi, the spirochetal agent of Lyme disease, infects the central
      nervous system (CNS), but the factors that mediate inflammation and neurologic
      dysfunction are not known. Sonicated B. burgdorferi stimulated in a concentration
      dependent manner the production of nitric oxide (NO) in glial-enriched primary
      cultures of neonatal rat brain cells via induction of NO synthase activity.
      Lipopolysaccharide (LPS) of Escherichia coli also stimulated nitrite accumulation
      in a concentration-dependent manner. Stimulation of NO production by B.
      burgdorferi sonicate and E. coli LPS was associated with increased levels of mRNA
      coding for the cytokine-inducible form of NO synthase. B. burgdorferi sonicate
      also stimulated release of interleukin-6, with a concentration-response
      relationship similar to that for its stimulation of nitrite production, as did E.
      coli LPS. A competitive antagonist of E. coli LPS, Rhodopseudomonas sphaeroides
      lipid A, inhibited LPS-induced stimulation of NO synthase activity but markedly
      potentiated that of B. burgdorferi, indicating that the initial triggering
      mechanism of B. burgdorferi is distinct from that of E. coli LPS. Induction of NO
      synthase by bacterial agents within the brain may represent a common pathway of
      CNS inflammation and neurotoxicity.

PMID- 7513329
TI  - Increased expression of pp60c-src in gastric mucosa of aged rats.
AB  - The relationship between proliferative activity and the expression of pp60c-src
      in gastric mucosa (oxyntic gland area) of young (4-month) and aged (24-month)
      Fischer 344 rats was examined. Gastric mucosal proliferative activity, as
      assessed by 5-bromo-2'-deoxyuridine (BrdU) immunoreactive cells, was found to be
      115% (p < .001) higher in aged than in young rats. This was associated with a 47%
      rise (p < .025) in overall tyrosine kinase (Tyr-k) activity and a 5-7-fold
      increase in autophosphorylation of four prominent protein bands with M(r) of 40,
      55, 60, and 70 kDa in gastric mucosal membranes. A similar phenomenon was also
      observed for Tyr-k activity of pp60c-src in that the aged rats revealed a 69% (p
      < .025) higher enzyme activity and a 5-fold rise in the extent of
      autophosphorylation of this protein when compared with the corresponding values
      from young animals. Increased Tyr-k activity of pp60c-src in the gastric mucosa
      of aged rats could in part be due to higher levels of this protein because the
      relative concentration of pp60c-src, as assessed by Western blot analysis, showed
      a 2-5-fold increase over the young animals. In addition, the relative
      concentration of c-src mRNA in the gastric mucosa of aged rats was also found to
      be 5-6-fold higher than in young animals. We suggest that pp60c-src may play a
      role in regulating gastric mucosal proliferative processes in the gastric mucosa
      of aged rats.

PMID- 7513333
TI  - Informatics in palliative care.
AB  - A computerized documentation system for palliative care would allow immediate
      availability of patient data and rapid evaluation of treatment. To develop such a
      system, many problems must be resolved, including choice of data and type of
      display. A preliminary screening of information and the introduction of codes to
      show some parameters are necessary to achieve a good result. We describe a
      program that allows data entry, storage of data, rapid display and printout of
      data, and recording of history, previous therapy, pathologic, physical, and
      laboratory findings, diagnosis, mechanisms and site of pain, drugs, and symptoms.
      Further improvements and problems are discussed.

PMID- 7513334
TI  - Successful control of intractable nausea and vomiting requiring combined
      ondansetron and haloperidol in a patient with advanced cancer.
AB  - Chemically induced nausea and vomiting is a common symptom of advanced cancer
      effected through stimulation of dopamine (D2) or serotonin (5-HT3) receptors
      located in the chemoreceptor trigger zone (CTZ). These may be blocked by
      therapeutic doses of haloperidol and ondansetron, respectively. This case,
      reporting on a single patient acting as her own control, establishes that
      combined blockade of these receptors is sometimes required to relieve intractable
      nausea and vomiting. It also demonstrates the value of clinical review, audit of
      care, and quality assurance in the palliative care setting.

PMID- 7513335
TI  - Cognitive impairment in a patient with a normal mini-mental state examination
      (MMSE).

PMID- 7513336
TI  - Withdrawal symptoms during therapy with transdermal fentanyl (fentanyl TTS)?

PMID- 7513337
TI  - Stimulation of HMG-CoA reductase as a consequence of phenobarbital-induced
      primary stimulation of cholesterol 7 alpha-hydroxylase in rat liver.
AB  - Among nine strains of rat, two were found that responded to phenobarbital
      treatment with increased activity of hepatic cholesterol 7 alpha-hydroxylase.
      This effect was maximal after 2-3 days of treatment and was then reduced.
      Interestingly the increased cholesterol 7 alpha-hydroxylase activity was
      associated with increased activity of hepatic HMG-CoA reductase in the two
      responding strains but not in the non-responding strains. In tissues other than
      the liver, HMG-CoA reductase activity was unaffected in responding rats. Most of
      the above stimulation occurred at a pretranslatory level and the mRNA levels
      corresponding to the two enzymes paralleled the activities. The phenobarbital
      treatment resulted in decreased content of free cholesterol in liver microsomes
      in a strain of rat that responded with increased cholesterol 7 alpha-hydroxylase
      activity. It was shown that depletion of cholesterol in the responding strain of
      rats by lymph fistulation also was associated with a parallel increase in levels
      of HMG-CoA reductase activity and mRNA. The findings are discussed in relation to
      the link between HMG-CoA reductase and cholesterol 7 alpha-hydroxylase. A primary
      upregulation of the cholesterol 7 alpha-hydroxylase by the cytochrome P450
      inducer phenobarbital can be expected to lead to increased consumption of
      cholesterol substrate. This consumption may result in a compensatory increase in
      the activity of the HMG-CoA reductase. It is suggested that such a mechanism is
      responsible for part of the covariation of the two enzyme systems under different
      conditions.

PMID- 7513338
TI  - Diagnosis of low back pain, secondary to prostate metastasis to the lumbar spine,
      by digital rectal examination and serum prostate-specific antigen.
AB  - OBJECTIVE: To present a case in which the initial diagnosis of spinal metastasis
      secondary to prostate cancer was established from findings of the digital rectal
      examination (DRE) and serum prostate-specific antigen (PSA) analysis. CLINICAL
      FEATURES: A 79-yr-old black male was seen after suffering from low back pain for
      1 month. Urinary frequency and nocturia were associated symptoms. Abnormal
      findings on the DRE and serum PSA determination suggested a preliminary diagnosis
      of spinal metastases secondary to prostate cancer. Subsequent referral for biopsy
      and bone scan yielded the final diagnosis of prostate adenocarcinoma with spinal
      metastasis. Radiographs of the lumbosacral spinal region were inconclusive and
      results of routine laboratory tests (CBC, ESR, U/A) were within normal limits.
      INTERVENTION AND OUTCOME: The patient was referred for medical palliation of his
      condition. A bilateral orchiectomy was performed along with oral antiandrogen
      administration. At a consultation 8 months postoperatively, he reported to be
      free of pain. CONCLUSION: At least 40% of newly diagnosed cases of prostate
      cancer can be expected to have metastasized at the time of initial discovery.
      Routine use of DRE and serum PSA in patients complaining of low back pain who are
      at high risk for prostate cancer is recommended. However, mass screening with DRE
      or PSA in asymptomatic males is not recommended. There are no prospective studies
      showing evidence that mass screening for prostate cancer will reduce the
      mortality or morbidity rates from the disease.

PMID- 7513339
TI  - The distribution of hypothalamic nitric oxide synthase mRNA in relation to
      gonadotrophin-releasing hormone neurons.
AB  - Using probes for rat neural nitric oxide synthase (NOS) mRNA and GnRH mRNA, we
      performed in situ hybridization to survey NOS mRNA distribution within the
      hypothalamus of the male and female rat and sought evidence for its expression in
      GnRH neurons. The NOS cRNA probe was radiolabelled with 35S, and a digoxigenin
      labeled rat GnRH cRNA probe was used for double-label studies. NOS mRNA was
      localized in discrete hypothalamic areas, in grain clusters suggestive of
      individual neurons. NOS mRNA-positive cells were located mainly in the supraoptic
      and paraventricular nucleus, particularly overlying the magnocellular division.
      Rostrally, cells expressing NOS mRNA were especially prominent in the diagonal
      band of Broca, in a distribution very similar to GnRH neurons. Nevertheless, only
      one of 370 cells labeled for GnRH mRNA appeared to be positive for NOS mRNA. We
      conclude that NOS mRNA is located prominently in regions where CRH, AVP and
      oxytocin cells are located. NOS mRNA-positive cells are located in close
      proximity to GnRH neurons, but rarely do such neurons express NOS mRNA.

PMID- 7513340
TI  - Measuring insulin-like growth factors: why, where and how?

PMID- 7513341
TI  - Several insulin-like growth factor-I analogues and complexes of insulin-like
      growth factors-I and -II with insulin-like growth factor-binding protein-3 fail
      to mimic the effect of growth hormone upon lactation in the rat.
AB  - Lactation was suppressed in rats using a combined treatment of bromocriptine (to
      reduce prolactin concentrations) and a specific antiserum to rat GH administered
      twice daily for 2 days. When milk production had ceased, as determined by litter
      weight loss and the absence of milk in the stomachs of pups, attempts were made
      to reinitiate lactation using prolactin, GH, insulin-like growth factor-I (IGF-I)
      precomplexed to recombinant human IGF-binding protein-3 (hIGFBP-3) or IGF-I plus
      IGF-II precomplexed to hIGFBP-3. Despite the fact that all treatments except
      prolactin led to increases in serum IGFs and IGFBP-3, only prolactin and GH
      provoked the reinitiation of milk production as determined by increased litter
      weight gain, milk in the stomach of pups and a significant increase in the weight
      of the mammary glands. Since the mammary gland has been shown to produce IGFBPs
      which may inhibit IGF action we also tested three IGF-I analogues, R3-IGF-I, Long
      IGF-I and Long-R3-IGF-I. R3-IGF-I has a single amino acid substitution (Glu to
      Arg) at position 3 whereas Long-IGF-I has a 13 amino acid N-terminal extension.
      These modifications dramatically reduce the ability of these analogues to bind to
      IGFBPs although they remain active at the IGF-I receptor. Such IGF analogues
      would therefore be expected to be active irrespective of the production of
      inhibitory IGFBPs. However, none was effective in reinitiating lactation, even at
      doses which have been shown to be biologically effective in terms of nitrogen
      retention.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513342
TI  - Comparison of the effectiveness of various procedures for reducing or eliminating
      insulin-like growth factor-binding protein interference with insulin-like growth
      factor-I radioimmunoassays on porcine sera.
AB  - We have examined the efficacy of various methods for reducing the interference of
      insulin-like growth factor-binding proteins (IGFBPs) with insulin-like growth
      factor-I (IGF-I) radioimmunoassays (RIAs) run on porcine sera. Acid-ethanol (AE)
      extraction, AE extraction followed by cryoprecipitation, glycyl-glycine (GG)
      extraction, GG extraction followed by Sephadex G-50 chromatography in 1 mol
      acetic acid/l (GG/G-50), and Sep-Pak chromatography were analysed. To provide a
      range of IGF-I and IGFBP levels, sera obtained from control, hypophysectomized,
      diabetic and somatotrophin-treated pigs were used. Recoveries of IGF-I added to
      sera prior to treatments other than Sep-Pak chromatography ranged from 85 to 105%
      and were not significantly different. In contrast, Sep-Pak chromatography gave
      extremely variable recoveries. 125I-Labelled IGF-I ligand blotting showed that GG
      extraction followed by acid G-50 chromatography was by far the most effective
      method of removing or inactivating IGFBPs in porcine sera. Consequently, this
      procedure was used as a standard against which to compare other extraction
      procedures. GG extraction alone removed or inactivated low molecular weight
      binding proteins but appeared to have little effect on IGFBP-3. AE extraction
      reduced the level of IGFBP-3 but had little effect on lower molecular weight
      binding proteins. Even though none of the tested procedures completely removed or
      inactivated the binding proteins, all samples yielded IGF-I displacement curves
      that were parallel to that obtained for IGF-I standard. Despite yielding parallel
      displacement curves, sera extracted by various methods gave dramatically
      different apparent IGF-I levels when subjected to IGF-I RIA.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7513343
TI  - Changes in hepatic insulin-like growth factor-binding proteins -1, -2 and -3 mRNA
      levels in rats with altered thyroid status.
AB  - Changes in thyroid status have a major effect on the GH/insulin-like growth
      factor (IGF) axis. The majority of IGF in the circulation is bound to specific
      IGF-binding proteins (IGFBPs) of which six have been cloned and sequenced. We
      have studied changes in hepatic gene expression of IGFBP-1, -2 and -3, in male
      Wistar rats rendered hyperthyroid (thyroxine, 200 micrograms/kg per day) or
      hypothyroid (propylthiouracil, 0.1% daily). Littermates of the same age were used
      as controls (n = 6 in each group). Thyroxine was measured by radioimmunoassay,
      and hepatic IGFBP-1, -2 and -3 mRNA levels by Northern blot analysis using
      specific rat cDNA probes with a 28S ribosomal probe as a loading control. Mean +/
      S.E.M. thyroxine levels were 247.0 +/- 44.5 (hyperthyroid group), < 9.0
      (hypothyroid group) and 76.0 +/- 4.5 nmol/l (control group). IGFBP-1 and -2 mRNA
      levels in the hypothyroid animals compared with the controls were significantly
      increased, but similar levels of expression were found in thyrotoxic and control
      rats. IGFBP-3 mRNA levels in hypothyroid animals were decreased, and increased in
      thyrotoxic animals. Thus, in the adult rat, hypothyroidism is associated with
      increased hepatic IGFBP-1 and -2 gene expression, but decreased IGFBP-3 gene
      expression, while in thyrotoxicosis there are normal IGFBP-1 and -2 mRNA levels
      but increased IGFBP-3 gene expression. These results suggest that there is
      specific and different transcriptional regulation for IGFBP-1, -2 and -3 in hypo-
      and hyperthyroid rats.

PMID- 7513344
TI  - Comparison of extraction methods for insulin-like growth factor-binding proteins
      prior to measurement of insulin-like growth factor-I in undernourished neonatal
      and adult rat serum.
AB  - Insulin-like growth factors (IGFs) are considered to be endocrine regulators
      during development, and different species have been used for the study of these
      factors during the perinatal period. The neonatal rat is a very useful model
      widely utilized to study endocrine alterations throughout the developmental
      period; few references in the literature present the neonatal rat as a model for
      the study of IGFs however. This study was undertaken to compare two extraction
      methods, acid-ethanol cryoprecipitation (AEC) and formic acid-acetone (FA), for
      the removal of IGF-binding proteins (IGFBPs) from neonatal and adult rat serum in
      fed (control) and undernourished populations prior to measurement of IGF-I by
      radioimmunoassay (RIA). The IGF-I values obtained by RIA following AEC or FA
      extraction were compared with those obtained following gel filtration (GF), which
      is considered to be the reference method. Western ligand blotting was used to
      determine IGFBPs in unextracted serum and after AEC or FA extraction of serum
      from rats of 10 and 20 days of age and adult rats in both populations. Although
      serum IGF-I levels after AEC or FA in adult control rats were comparable with
      those obtained following GF, a significant correlation was found only after AEC
      extraction both in fed and undernourished adult rats. During the neonatal period,
      at 10 and 20 days, serum IGF-I levels after AEC or FA extraction were very
      different from those obtained after GF, especially in undernourished populations,
      and the correlation was very poor at 10 and 20 days of age in both populations
      studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513345
TI  - Effect of growth hormone on steroidogenesis, insulin-like growth factor-I (IGF-I)
      and IGF-binding protein-1 production and DNA synthesis in cultured human
      luteinized granulosa cells.
AB  - Numerous clinical and experimental observations have suggested that GH is
      important in ovarian function. We have investigated the effect of GH alone and GH
      in combination with FSH on the secretion of oestradiol, progesterone, insulin
      like growth factor-I (IGF-I) and IGF-binding protein-1 (IGFBP-1) and on
      [3H]thymidine incorporation in cultured human luteinized granulosa cells.
      Granulosa cells from patients undergoing treatment for in vitro fertilization
      were isolated and cultured for 2 days in culture medium with 10% serum. After
      this preincubation, the medium was removed and the cells were incubated with GH
      (1, 10 and 100 micrograms/l) with or without FSH in serum-free medium and in the
      presence of [3H]methylthymidine (2 microCi/ml). GH alone resulted in a
      significant dose-dependent increase of oestradiol (P < 0.05) and in IGFBP-1 (P <
      0.002) in the medium. The release of IGF-I was undetectable and there was no
      increase in [3H]thymidine incorporation with GH alone. Neither GH nor FSH alone
      stimulated granulosa cell proliferation or progesterone release, while the
      combination induced increases (P < 0.001) in both. The stimulatory effect of GH
      on steroidogenesis, IGFBP-1 production and granulosa cell proliferation supports
      a putative role for GH in the regulation of ovarian function.

PMID- 7513346
TI  - Human d-amphetamine drug discrimination: methamphetamine and hydromorphone.
AB  - Standard measures of subjective and discriminative effects of drugs were compared
      in 5 human volunteers. Subjects responded on a second-order color-tracking
      procedure, where 30 mg of d-amphetamine served as a discriminative stimulus for
      one response and its absence as the discriminative stimulus for another response.
      Self-reported subjective effects were assessed concurrently using the single-dose
      questionnaire, subscales of the Addiction Research Center Inventory, and several
      analogue rating scales. On different days following discrimination acquisition,
      varying doses of d-amphetamine, methamphetamine, and hydromorphone were
      administered. In these test sessions, either response was reinforced.
      Methamphetamine and d-amphetamine occasioned dose-related increases in d
      amphetamine appropriate responding; hydromorphone did not. Methamphetamine and d
      amphetamine occasioned dose-related increases in reports of the drug received
      being most like "speed"; hydromorphone occasioned dose-related increases in
      reports of the drug received being most like "dope." All three drugs occasioned
      dose-related increases in reports of drug liking, and increases in the morphine
      benzedrine group, amphetamine, and benzedrine group scales of the Addiction
      Research Center Inventory. This experiment demonstrated that although explicit
      discriminative control of behavior by a drug may covary with drug identification,
      it does not necessarily covary with other self-reported subjective effects. Thus,
      the complementary nature of the data provided by drug discrimination and standard
      subjective-effects measures provides quantitative and qualitative data useful in
      studying both relatively novel compounds and the behavioral biology of
      psychoactive drugs in general.

PMID- 7513347
TI  - The relations between neuroscience and human behavioral science.
AB  - Neuroscience seeks to understand how the human brain, perhaps the most complex
      electrochemical machine in the universe, works, in terms of molecules, membranes,
      cells and cell assemblies, development, plasticity, learning, memory, cognition,
      and behavior. The human behavioral sciences, in particular psychiatry and
      clinical psychology, deal with disorders of human behavior and mentation. The gap
      between neuroscience and the human behavioral sciences is still large. However,
      some major advances in neuroscience over the last two decades have diminished the
      span. This article reviews the major advances of neuroscience in six areas with
      relevance to the behavioral sciences: (a) evolution of the nervous system; (b)
      visualizing activity in the human brain; (c) plasticity of the cerebral cortex;
      (d) receptors, ion channels, and second/third messengers; (e) molecular genetic
      approaches; and (f) understanding integrative systems with networks and circadian
      clocks as examples.

PMID- 7513348
TI  - Processing units in word reading by disabled readers.
AB  - The article addresses the issue of whether disabled readers can be instructed to
      use within-word (multiletter) units. Several analogy methods were employed. In
      Experiments 1 and 2 short lists of words that differ in only one letter were
      repeatedly practiced. In Experiment 3 the subjects blended written and spoken
      words in which the place of segmentation was systematically manipulated. Subjects
      were tested in all experiments on the reading of practiced words, on nonpracticed
      words that orthographically as well as phonologically resemble the practiced
      words, and on nonpracticed nonsimilar words. The findings indicate that: (1) All
      types of practice were beneficial for the recognition of the practiced words. (2)
      Transfer to the reading of novel words appeared only when graphemic and
      orthographic aspects of words were strongly emphasized. (3) Transfer effects were
      based upon the improved handling of multiletter within-word units when word lists
      with auditory prompts were practiced, but on improved (single) letter-sound
      conversions when the analysis and synthesis of isolated words and word parts was
      trained. (4) At least in Dutch, segmentations according to the onset-rime
      principle were not more useful than segmenting written and spoken words at other
      boundaries.

PMID- 7513350
TI  - Age affects brain protein synthesis in rats.
AB  - The purpose of the present study was to determine whether age affected the rate
      of brain protein synthesis in rats. Experiments were conducted on three groups of
      rats, ages 4, 7 or 24 wk. The fractional rates of protein synthesis in brain,
      liver and kidney decreased and the RNA concentration (mg RNA/g protein) declined
      with age. In brain, liver and kidney, the RNA concentrations were significantly
      correlated with the fractional rates of protein synthesis. The RNA activity [g
      protein synthesized/(g RNA.d)] was not related to the fractional rate of protein
      synthesis in any organs except cerebral cortex. The results suggest that the rate
      of protein synthesis in brain declines with age after weaning, and that RNA
      concentration is at least partly related to the fractional rate of brain protein
      synthesis.

PMID- 7513349
TI  - Cyclic nucleotide-gated channels of rat olfactory receptor cells: divalent
      cations control the sensitivity to cAMP.
AB  - cAMP-gated channels were studied in inside-out membrane patches excised from the
      apical cellular pole of isolated olfactory receptor cells of the rat. In the
      absence of divalent cations the dose-response curve of activation of patch
      current by cAMP had a KM of 4.0 microM at -50 mV and of 2.5 microM at +50 mV.
      However, addition of 0.2 or 0.5 mM Ca2+ shifted the KM of cAMP reversibly to the
      higher cAMP concentrations of 33 or 90 microM, respectively, at -50 mV. Among
      divalent cations, the relative potency for inducing cAMP affinity shifts was:
      Ca2+ > Sr2+ > Mn2+ > Ba2+ > Mg2+, of which Mg2+ (up to 3 mM) did not shift the KM
      at all. This potency sequence corresponds closely to that required for the
      activation of calmodulin. However, the Ca(2+)-sensitivity is lower than expected
      for a calmodulin-mediated action. Brief (60 s) transient exposure to 3 mM Mg2+,
      in the absence of other divalent cations, had a protective effect in that
      following washout of Mg2+, subsequent exposure to 0.2 mM Ca2+ no longer caused
      affinity shifts. This protection effect did not occur in intact cells and was
      probably a consequence of patch excision, possibly representing ablation of a
      regulatory protein from the channel cyclic nucleotide binding site. Thus, the
      binding of divalent cations, probably via a regulatory protein, controls the
      sensitivity of the cAMP-gated channels to cAMP. The influx of Ca2+ through these
      channels during the odorant response may rise to a sufficiently high
      concentration at the intracellular membrane surface to contribute to the
      desensitization of the odorant-induced response. The results also indicate that
      divalent cation effects on cyclic nucleotide-gated channels may depend on the
      sequence of pre-exposure to other divalent cations.

PMID- 7513351
TI  - [Evaluation of the effects of nasal decongestants with acoustic rhinometry].
AB  - Acoustic rhinometry is a new method of evaluating the geometrical distributions
      of the cross-section and volume of the nasal cavity. Its characteristics are that
      of a nontraumatic procedure requiring minimal time for measurements. Eight males
      (27-39 years old) without nasal lesions were investigated with acoustic
      rhinometry before and after unilateral administrations of decongestants.
      Conventional nasal decongestants such as naphazolin nitrate 0.1% (Privina) and
      tetrahydrozoline hydrochloride 0.1%, as well as prednisolone 0.02% (Cor-tyzine),
      were used in solutions diluted 10 or 100 times. As to the method of decongestant
      application, we adopted the head tilt method, in the successive order of
      backward, lateral (toward the non-application side) tilt and backward. Each
      position was maintained for 30 seconds. Minimal cross sectional area of the nasal
      cavity, and nasal volume were evaluated with acoustic rhinometry. After the
      application of nasal drops, the minimal cross sectional area increased within 10
      minutes, followed by a plateau level for one hour. With the application of nasal
      decongestants, an I-notch, corresponding to the nasal valve, was unchanged,
      whereas the C-notch, corresponding to the anterior and of the inferior turbinate,
      often shifted upwards. Thus, the minimal cross sectional area changed from an I
      notch to a C-notch location. The volume of the nasal cavity increased within 10
      minutes, and maintained a plateau level for one hour which was similar to that of
      the minimal cross sectional area. Changes in the ratio of the minimal cross
      sectional area were greater for less diluted solutions. Changes in the ratio of
      the nasal cavity were similar to those of the minimal cross sectional area.

PMID- 7513352
TI  - The observation of angiogenin and basic fibroblast growth factor gene expression
      in human colonic adenocarcinomas, gastric adenocarcinomas, and hepatocellular
      carcinomas.
AB  - Using digoxigenin-labelled, synthetic oligonucleotide probe cocktails of
      angiogenin and bFGF genes, the expression of the two genes was observed by in
      situ hybridization in ten colonic adenocarcinomas, seven gastric adenocarcinomas,
      and four hepatocellular carcinomas. The angiogenin gene was expressed in eight of
      the ten cases of colonic adenocarcinoma and in all of the four cases where
      dysplastic glands were found. Angiogenin expression was evident in four of the
      seven cases of gastric adenocarcinoma. bFGF expression was detected in only five
      of the seven gastric carcinoma cases. The mRNAs for angiogenin and bFGF were
      mainly cytoplasmic in distribution and were only occasionally seen in the nuclei
      of the positive cells. Neither the angiogenin gene mRNA nor the bFGF mRNA was
      expressed in the four cases of hepatocellular carcinoma. It is postulated that
      the angiogenin gene may play an important role in angiogenesis in colonic
      adenocarcinomas; in gastric cancers, both angiogenin and bFGF were involved in
      this process. For hepatocellular carcinomas, neither angiogenin nor bFGF
      production appeared to be related to angiogenesis.

PMID- 7513353
TI  - The prognostic significance of immunohistochemically detected lymph node
      micrometastases in colorectal carcinoma.
AB  - Micrometastases have been detected by immunocytochemical means in the lymph nodes
      of patients with otherwise node-negative cancer of the colon and rectum. This
      study examines the incidence and prognostic significance of nodal micrometastases
      in Dukes' B carcinoma. Five hundred and fifty-nine lymph nodes from 77 cases of
      Dukes' B carcinoma were examined for lymph node micrometastases by
      immunocytochemical staining for cytokeratin AE1:AE3. Micrometastases were
      detected in 19 cases (25 per cent). Cell clusters were present in ten cases, the
      remaining nine cases displaying only single cells. The presence of
      micrometastases was unrelated to age (P = 0.06), sex (P = 0.32), tumour site (P =
      0.37), tumour size (P = 0.67), or tumour differentiation (P = 0.66). Ten-year
      survival estimates by the Kaplan-Meier lifetable method was 47 per cent in
      patients with and without micrometastases (chi 2 = 0.35 and 1 df, P = ns). The
      presence of nodal micrometastases detectable only by immunocytochemistry in
      patients with Dukes' B colorectal cancer does not justify reassignment to a more
      advanced disease stage.

PMID- 7513355
TI  - Pharmacokinetic and pharmacodynamic effects of coadministration of
      methylprednisolone and tacrolimus in rabbits.
AB  - Tacrolimus (FK 506) is used for treatment of various organ transplantations in
      combination with corticosteroids. Rabbits are a good animal model for
      pharmacokinetic studies of these drugs. The i.v. administration of
      methylprednisolone (MP; 1.25 mg/kg) (sodium succinate) at 0.5 hr after tacrolimus
      (0.15 mg/kg) did not influence the disposition of these drugs in rabbits.
      Clearances of MP were 0.45 liters/hr/kg after given alone and 0.48 liter/hr/kg
      after tracrolimus. The plasma and whole blood clearances of tacrolimus were 2.18
      and 0.21 and 2.35 and 0.19 liters/hr/kg after separate and joint administration
      with the steroid. The concentrations of corticosterone were variable in all
      groups and was not useful as a pharmacodynamic parameter. Whole blood histamine
      concentrations as a marker for basophils did not change after drug
      administration, but increased over several weeks of experiments. Helper-T cells
      in rabbits as in humans show a circadian rhythm with an acrophase at 1:00 A.M. MP
      and tacrolimus decreased the number of circulating helper-T cells with IC50
      values of 23 ng/ml for MP and 6.7 ng/ml for tacrolimus. After coadministration of
      these drugs, an interaction occurs, but the nature (additive or antagonistic) of
      this interaction was not clear. The IC50 of tacrolimus for in vitro inhibition of
      lymphocyte proliferation was 0.39 ng/ml (0.47 nM) and 1.02 ng/ml (2.73 nM) for
      MP. The maximum percentage of inhibition was 94.6% for tacrolimus and 64.9% for
      MP. The interaction between low concentrations of tacrolimus (0.1-0.3 ng/ml) and
      MP was additive, but mild antagonism was observed at higher concentration of
      tacrolimus (1 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513356
TI  - Effects of duloxetine, an antidepressant drug candidate, on concentrations of
      monoamines and their metabolites in rats and mice.
AB  - Duloxetine, (+)-N-methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamine, is an
      inhibitor of the serotonin and norepinephrine neuronal transporters (Wong et al.,
      1993). In mice, duloxetine antagonized the depletion of brain serotonin by p
      chloroamphetamine (ED50 = 2.5 mg/kg, i.p.) and the depletion of heart
      norepinephrine by 6-hydroxydopamine (ED50 = 1.1 mg/kg, i.p.). Brain
      concentrations of 5-hydroxyindoleacetic acid were decreased by duloxetine at 2 hr
      after doses of 1, 3 and 10 mg/kg and at 1 to 8 hr (but not 24 hr) after a 10
      mg/kg i.p. dose of duloxetine. Duloxetine antagonized norepinephrine depletion in
      frontal cortex, but not dopamine depletion in striatum, after treatment of mice
      with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In rats, duloxetine decreased
      brain 5-hydroxyindoleacetic acid dose-dependently for up to 8 hr and decreased
      serotonin turnover measured by the accumulation of 5-hydroxytryptophan in rat
      hypothalamus after decarboxylase inhibition. In rats, duloxetine antagonized the
      depletion of brain serotonin by p-chloramphetamine and the depletion of
      norepinephrine and epinephrine in hypothalamus after i.c.v. injection of 6
      hydroxydopamine. In vitro, duloxetine had little effect on either type A
      (serotonin as substrate) or type B (phenylethylamine as substrate) monoamine
      oxidase, IC50 concentrations being above 10(-5) M. These data extend evidence
      that duloxetine inhibits serotonin and norepinephrine transporters in vivo,
      actions that may lead to therapeutic efficacy in mental depression.

PMID- 7513357
TI  - Selective effects of alcohols on gamma-aminobutyric acid A receptor subunits
      expressed in human embryonic kidney cells.
AB  - Several previous studies implicated alpha 6 and gamma 2L subunits as potential
      determinants of gamma-aminobutyric acid A (GABAA) receptor channel sensitivity to
      alcohol modulation. The effects of ethanol and n-octanol were studied on GABA
      induced currents in human embryonic kidney cells transfected to express one of
      three different GABAA receptor channel subunit combinations: alpha 1 beta 2 gamma
      2S, alpha 6 beta 2 gamma 2S or alpha 6 beta 2 gamma 2L. No increase in the
      current amplitude of any subunit combination was observed after the coapplication
      of GABA and physiological concentrations (10-100 mM) of ethanol. By contrast, the
      coapplication of GABA and 100 microM octanol increased the current amplitude by
      50% to 100% in all three subunit combinations. Octanol produced a shift of the
      current dose-response curve toward lower concentrations of GABA. Ethanol was
      effective in increasing the rate of desensitization produced by higher
      concentrations of GABA in the alpha 6 beta 2 gamma 2S cells but not the alpha 1
      beta 2 gamma 2S combination. This ethanol-induced modification of desensitization
      was not altered by the presence of the protein kinase inhibitor 1-(5
      isoquinolinesulfonyl)-2-methylpiperazine (H-7). These experiments indicate that
      the presence of alpha 6 or gamma 2L subunits, in itself, does not result in the
      potentiation of GABA-induced currents by ethanol, as described in some reports.
      However, the presence of either the alpha 6 or alpha 1 subunit may determine
      whether the desensitization rate of the GABAA current is affected by the alcohol.

PMID- 7513354
TI  - Glycosylphosphatidylinositol (GPI)-anchored membrane proteins are constitutively
      down-regulated in psoriatic skin.
AB  - Hyperproliferation of keratinocytes (KCs) in psoriasis has been found to be
      associated with excessive activation of a phospholipase C (PLC)/protein kinase C
      (PKC) signal transduction system. The molecular species of PLCs which are
      activated in psoriasis have not been thoroughly investigated. It was envisaged
      that if glycosylphosphatidylinositol (GPI)-specific PLC was activated in the
      membrane of psoriatic epidermal cells, it would render these cells devoid of
      those proteins which are anchored to the cell membrane through their GPI moiety.
      In order to test this possibility, four GPI proteins (CD16, CD55, CD58, and CD59)
      were determined immunohistochemically in normal and psoriatic skin. In normal
      skin, CD55 and CD59 were strongly expressed on epithelium and vascular
      structures, whereas CD16 and CD58 were strongly expressed only on epithelium. The
      expression of all four GPI proteins was decreased in non-lesional psoriatic skin
      and virtually abolished in lesional psoriatic skin. A control transmembrane
      protein, CD46, was strongly expressed in normal and non-lesional psoriatic skin,
      and its expression was not significantly decreased in psoriatic lesions. The
      absence or reduction of GPI proteins was not seen in the lesions of several other
      inflammatory and proliferative diseases studied.

PMID- 7513358
TI  - Effects of nitric oxide-related agents on rat testicular function.
AB  - The effects of nitric oxide (NO)-related agents on testicular function were
      examined in male rats with measurements of serum luteinizing hormone, serum
      testosterone, testicular interstitial fluid (TIF) testosterone, and TIF volumes.
      Serum and TIF testosterone levels and luteinizing hormone secretion were
      significantly decreased by the NO donor, isosorbide dinitrate (ISDN), and the NO
      synthase (NOS) substrate, L-arginine methyl ester, a source for the endogenous
      production of NO. The effects of ISDN on TIF volumes were inconsistent, but L
      arginine methyl ester decreased TIF formation in a dose-dependent manner. In
      addition, ISDN dose dependently suppressed testosterone secretion stimulated by
      human chorionic gonadotropin treatment, suggesting that the effects on
      testosterone secretion were independent of changes in secretion of the endogenous
      gonadotropin luteinizing hormone. ISDN, L-arginine methyl ester, and the
      endogenous NOS substrate L-arginine completely blocked testosterone secretion
      stimulated by the NOS inhibitor NG-nitro-L-arginine methyl ester (NAME), whereas
      the relatively inactive NOS substrate, D-arginine, only partially blocked NAME
      stimulated testosterone secretion. Hydralazine and nicardipine, two vasodilators
      that do not exhibit prominent NO-related effects, also blocked basal testosterone
      secretion and testosterone secretion stimulated by the vasoconstrictor
      NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513359
TI  - Influence of excitatory amino acid receptor subtypes on the electrophysiological
      activity of dopaminergic and nondopaminergic neurons in rat substantia nigra.
AB  - In vivo electrophysiological recording methods were used to evaluate the effects
      of selective and nonselective agonists for excitatory amino acid (EAA) receptor
      subtypes on the activity of dopaminergic (DA) and nondopaminergic (non-DA)
      neurons in the substantia nigra of chloral hydrate-anesthetized rats.
      Microiontophoretic administration of (+/-)-alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA), 2-carboxy-4-(1-methyl-ethenyl)-3
      pyrrolidinacetate (kainate), N-methyl-D-aspartate (NMDA) and glutamate excited
      neurons with an apparent rank order of potency of AMPA = kainate = glutamate >
      NMDA on DA neurons, and AMPA = kainate > glutamate = NMDA on non-DA neurons.
      These agonists also changed the firing pattern of DA neurons, which displayed an
      increase in burst-firing and a reduction in the regularity of the firing pattern.
      Regularity of firing was indexed by the variation coefficient of a sample of
      interspike intervals. The apparent potencies of the four agonists to increase
      burst-firing and variation coefficient were similar to their potencies to
      increase neuronal firing rate. Blockade of NMDA receptor function by
      coiontophoresis of 5R,10S-(+/-)-5-methyl-10,11-dihydro-5H-dibenzo[and]cyclohepten
      5,1 0-imine hydrogen maleate (MK-801), a selective noncompetitive NMDA
      antagonist, did not alter kainate-induced changes in firing rate and firing
      pattern, which indicated that kainate-induced increases in burst-firing were not
      dependent on concomitant NMDA receptor activation by endogenous excitatory amino
      acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513360
TI  - Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP
      accumulation in rat striatum.
AB  - Although the acute effects of organophosphorus esters are generally ascribed to
      inhibition of acetylcholinesterase, work in this laboratory and others indicates
      that organophosphorus insecticides also interact directly with cholinergic
      receptors. The current study verifies that the insecticide O,O-diethyl O-3,5,6
      trichloro-2-pyridinyl phosphorothionate (chlorpyrifos) and its oxon metabolite
      inhibits acetylcholinesterase (AChE). The metabolite inhibits rat brain AChE
      three orders of magnitude more rapidly than chlorpyrifos. In addition to their
      ability to inhibit AChE, these compounds were shown to interact directly with
      muscarinic receptors of rat striatum. The oxon metabolite bound at low
      concentrations to muscarinic receptors labeled by the muscarinic agonist [3H] cis
      methyldioxolane; chlorpyrifos oxon bound with an IC50 value of 22.1 +/- 3.6 nM.
      The receptors bound by chlorpyrifos oxon account for approximately 30% of
      muscarinic receptors of the striatum and are of the m2 subtype. The binding of
      chlorpyrifos oxon to the m2 receptor results in a covalent modification of the
      receptor that does not interfere with the ability of the receptor to interact
      with the agonist carbachol. This receptor modification may be responsible for the
      inhibition of adenylate cyclase activity by chlorpyrifos oxon. The oxon inhibited
      adenylate cyclase with an IC50 of 155 +/- 78 nM. The inhibition of adenylate
      cyclase activity was not blocked by atropine and was additive to that produced by
      carbachol. The altering of postreceptor signal transduction by chlorpyrifos oxon
      may interfere with normal cellular signaling, thereby disturbing neurological
      function. Direct interaction of chlorpyrifos oxon with muscarinic receptors and
      associated signal transduction is a potential mechanism of neurotoxicity that is
      independent of AChE inhibition.

PMID- 7513361
TI  - Developmental expression of human microsomal epoxide hydrolase.
AB  - Microsomal epoxide hydrolase (mEH) is a critical biotransformation enzyme that
      catalyzes the hydrolysis of a large number of epoxide intermediates, which arise
      frequently from the oxidation of pharmaceutical and environmental compounds by
      the cytochrome P450 mixed function oxygenase system. The enzyme mEH has been
      implicated directly as a key determinant of certain chemically initiated cancers
      and developmental toxicities. To evaluate mEH expression in human tissues and
      provide a framework for assessing the relative risk in the fetus to potential
      developmental toxins, in the current study, the authors characterized mEH in
      human tissues as a function of gestational age. Analyses included enzymatic
      activity determinations, immunochemical quantitation of protein levels and RNA
      hybridization assays. With respect to activity, hepatic mEH enzymatic levels were
      strongly correlated with increasing gestational age (r = .82, P < .001).
      Similarly, mEH activity levels in the liver were highly correlated with protein
      contents (r = .93, P < .001). However, mEH enzymatic activity in the fetal lung
      did not exhibit similar concordance nor did measured RNA levels appear to
      correlate with enzymatic activity levels in fetal or adult tissue samples. Of the
      fetal tissues surveyed, the liver and adrenal glands exhibited the highest levels
      of detectable mEH RNA, followed by the lung and kidney. These data suggest that
      post-transcriptional regulatory pathways may be important in determining
      constitutive levels of mEH functional activity and that fetuses during early
      gestation may be uniquely sensitive to the presentation of epoxide-containing
      xenobiotics compared with fetuses at later stages of development.

PMID- 7513362
TI  - The sigma receptor ligand (+/-)-BMY 14802 prevents methamphetamine-induced
      dopaminergic neurotoxicity via interactions at dopamine receptors.
AB  - The possibility that compounds which interact with the putative sigma receptor
      might influence the dopaminergic neuropathology produced by the administration of
      methamphetamine (METH) to mice was investigated. (+/-)-BMY 14802 [alpha-(4
      fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol hydrochloride]
      attenuated METH-induced dopaminergic neuropathology whereas several other sigma
      acting compounds such as R-(+)-3-(3-hydroxyphenyl)-N-propylpiperidine
      hydrochloride, 1,3-di-o-tolyl-guanidine, rimcazole, clorgyline or (-)-butaclamol
      did not alter neurotoxicity produced by this central nervous system stimulant. (
      )-BMY 14802, which has a lower affinity for the sigma site than (+)-BMY 14802,
      was more potent than (+)-BMY 14802 in antagonizing METH-induced neuropathology.
      In addition, the ketone metabolite (BMY 14786; alpha-(4-fluorophenyl)-4-(5-fluoro
      2-pyrimidinyl)-1-piperazine-butanone hydrochloride), which is a major metabolite
      formed from (-)-BMY 14802, also attenuated the METH-induced effects. (+/-)-BMY
      14802 pretreatment of mice prevented the reduction in D1 and D2 dopamine receptor
      number produced by the systemic administration of N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline and demonstrates that (+/-)-BMY 14802 and/or its metabolites
      interact with the dopamine receptor subtypes. Taken together, these findings
      suggest that the protective effect of (+/-)-BMY 14802 against METH-induced
      neuropathology is mediated, at least in part, through dopamine receptor
      antagonism. Furthermore, the failure of other sigma-acting compounds to alter
      METH-induced neurotoxicity indicates that the putative sigma receptor is unlikely
      to be an important mediator in this type of neuropathology.

PMID- 7513363
TI  - An evaluation of serum and tissue bound immunoglobulins in prostatic diseases.
AB  - In forty-four patients with different prostatic lesions serum immunoglobulins and
      tissue deposited immunoglobulins were studied by single radial immunodiffusion
      technique, and direct immunofluorescence and immunoperoxidase (PAP) methods
      respectively. Serum IgM levels were found reduced only in patients with prostatic
      carcinomas (80% of cases) as compared to controls. Serum IgA levels showed stage
      dependence in prostatic carcinoma being more raised in advanced malignancy (stage
      C and D) than in localized ones (stage B). Localization of immunoglobulins
      particularly IgM, was characteristically found in stroma and lumen along with
      intracellular localization in prostatic carcinoma; while normal and benign
      lesions of prostate only showed characteristic 'necklace' pattern. Also the
      intensity of deposits of immunoglobulins in poorly differentiated prostatic
      carcinomas was markedly low as compared to well differentiated carcinomas
      indicating lowered local immunological response in former. In prostatitis, IgA
      was also found localized in lumen indicating the immunological defence against
      infection by secretory antibody (IgA).

PMID- 7513364
TI  - Pregnancy after treatment of epithelioid hemangioendothelioma. A case report.
AB  - Pregnancy occurred in a woman who had undergone hepatic, cerebral and myocardial
      resection of epithelioid hemangioendotheliomas (EHEs). The overall course of her
      pregnancy did not seem to be affected by the prior EHEs, though the pregnancy was
      complicated by preterm delivery. The patient was observed to have elevated
      maternal serum alpha-fetoprotein (MSAFP); a complete workup found no
      abnormalities in the fetus, and a relationship between the EHEs and elevated
      MSAFP was not apparent. Because of the unknown contribution of EHE to MSAFP,
      inclusion of targeted (level II) ultrasound and possibly amniocentesis seem
      appropriate to prenatally diagnose structural anomalies and ensure a normal
      karyotype.

PMID- 7513366
TI  - Angiogenesis research spreads to clinic.

PMID- 7513365
TI  - Evolution of prothrombin: isolation and characterization of the cDNAs encoding
      chicken and hagfish prothrombin.
AB  - The cDNA sequences of chicken and hagfish prothrombin have been determined. The
      sequences predict that prothrombin from both species is synthesized as a prepro
      protein consisting of a putative Gla domain, two kringle domains, and a two-chain
      protease domain. Chicken and hagfish prothrombin share 51.6% amino acid sequence
      identity (313/627 residues). Both chicken and hagfish prothrombin are
      structurally very similar to human, bovine, rat, and mouse prothrombin and all
      six species share 41% amino acid sequence identity. Amino acid sequence
      alignments of human, bovine, rat, mouse, chicken, and hagfish prothrombin suggest
      that the thrombin B-chain and the propeptide-Gla domain are the regions most
      constrained for the common function(s) of vertebrate prothrombins.

PMID- 7513368
TI  - [Mucin histochemical study of differentiated adenocarcinoma of stomach].
AB  - The mucin phenotypic expression of gastric differentiated adenocarcinoma was
      investigated by mucin histochemical method. Seventy-nine advanced gastric
      carcinomas, which showed histologically differentiated type (well and moderately
      differentiated type) in the mucosa, were classified into four types; gastric type
      (30.4%), intestinal type (19.0%), combined type with both gastric and intestinal
      phenotype (45.6%) and lack of mucin type (5.1%). Moreover, differentiated
      adenocarcinoma of gastric type were subclassified into foveolar (F) type (37.5%),
      pyloric gland (P) type (37.5%) and mixed (M) type with foveolar and pyloric type
      (25.0%). Both gastric type and intestinal type differentiated adenocarcinoma were
      apt to change to undifferentiated type in the invasive lesion below the
      submucosa. On the contrary, carcinoma of combined type changed to
      undifferentiated type with significantly lower incidence than the former two
      type. F-type differentiated adenocarcinoma tended to develop scirrhous or non
      solid type infiltration and carcinoma of P-type showed medullary or solid growth
      with significantly higher incidence than the other type. Mucin phenotypic
      expressions of differentiated adenocarcinoma had much to do with the mode of
      growth and infiltration of cancer in the gastric wall below the submucosal layer.

PMID- 7513367
TI  - Comparison of lesions induced by intra-articular injections of quinolones and
      compounds damaging cartilage components in rat femoral condyles.
AB  - Twenty-five microliters of a 2% saline solution of levofloxacin (LVFX) or
      ciprofloxacin (CPFX) was injected every other day for 2 wk into the knee joint
      space of CD rats (weighing 62.7-86.7 g) from the age of 3 wk. Early in the course
      of injection, histologic examination revealed chondrocyte necrosis without marked
      matrix change in the articular cartilage of the femoral condyles adjacent to the
      intercondylar groove. After 7 injections, the surface and intermediate zones of
      the articular cartilage showed extensive necrosis, sometimes with cavity
      formation in the center of the same portion. Papain completely depleted matrix
      basophilia in all zones throughout the condyle and caused cartilage necrosis with
      cavity formation. One injection of iodoacetic acid caused necrosis of almost all
      chondrocytes over the entire condyle, but chondrocytes sometimes remained alive
      in the portion where cavity formation was induced by quinolones. Chondroitinase
      depleted the matrix basophilia, and sometimes produced necrotic areas. DNA
      synthesis inhibitors n-ethylmaleimide, CPT-11, and etoposide (VP-16) caused
      chondrocyte necrosis, but never caused cavities in the articular cartilage. The
      DNA synthesis inhibitors n-ethylmaleimide, CPT-11, and hydroxyurea were
      administered concurrently with po LVFX administration and significantly increased
      the incidence of LVFX-induced cavity formation. n-Ethylmaleimide was the most
      effective of all the inhibitors. The quinolone-induced cavity formation is
      suggested to be site specific in the articular cartilage of rat femoral condyles.
      The depletion of matrix proteoglycans and chondrocyte necrosis may be necessary,
      although insufficient, to produce such lesions. Disruption of the collagen
      framework is suspected to contribute to their development. Involvement of altered
      DNA metabolism may play a role in the chondrocyte necrosis that occurs early in
      the specific sites.

PMID- 7513369
TI  - [Effects of 16,16-dimethyl prostaglandin E2 on pancreatic exocrine function in
      vivo and in vitro in rat experiments].
AB  - The effects of exogenous and endogenous prostaglandin on rat pancreatic exocrine
      function were investigated in vivo and in vitro. Under stimulation by endogenous
      CCK or exogenous caerulein, protein output was significantly reduced by
      intravenous drip infusion of 16,16-dimethyl prostaglandin E2 (DMPGE2), and under
      stimulation by exogenous secretin, volume and bicarbonate output were markedly
      reduced by DMPGE2. Amylase release from isolated pancreatic acini was
      significantly reduced by DMPGE2 under stimulation by 10(-11)-3 x 10(-11) M CCK-8,
      and was not influenced by DMPGE2 under stimulation by secretin or by indomethacin
      under stimulation by caerulein. Basal amylase release was not influenced by
      DMPGE2 or indomethacin. Basal cellular cyclic AMP and cyclic GMP contents were
      not influenced by DMPGE2, and elevated cyclic GMP content under stimulation by
      caerulein was significantly reduced by DMPGE2. These findings suggest that
      pancreatic enzyme secretion is reduced by DMPGE2 under stimulation by
      physiological or pharmacological concentration of CCK, and one of which mechanism
      is direct effect of DMPGE2 on pancreatic acini, may be coupling with
      phosphatidylinositol breakdown system and without cyclic AMP.

PMID- 7513370
TI  - Effect of adult continuing wh-questions on conversational participation in
      children with developmental disabilities.
AB  - Children with developmental disabilities often converse less frequently than
      their developmentally matched peers. This low conversational participation can
      cause problems for the children's future language and discourse development. The
      purpose of this experimental study was to test the hypothesis that adult topic
      continuing wh-questions would elicit topic continuations in children with
      relatively low language ability, but not in children with relatively high
      language ability. Twenty-three children with developmental delays interacted with
      an adult who conducted two play sessions. In each session, the adult used a
      different interaction style. The two styles differed in the adult's use of topic
      continuing wh-questions. Results indicate that adult use of topic-continuing wh
      questions supported the use of child continuations in children at all language
      levels. The type of continuations (single word versus multiword) that were
      elicited depended on the language level of the children. Clinical implications
      are discussed.

PMID- 7513371
TI  - Induction of interleukin-2 receptor alpha chain expression of immature acute
      myelocytic leukemia cells.
AB  - Leukemic cells from 27 adult patients with acute myelocytic leukemia (AML) were
      investigated to determine the cell surface inducibility of interleukin-2 receptor
      (IL-2R) in in vitro culture with and without interleukin-1 beta (IL-1 beta). IL
      2R alpha chain (IL-2R alpha) was induced on leukemic cells in 11 of 27 cases.
      Most of the cases could induce IL-2R alpha spontaneously without IL-1 beta, while
      the IL-2R beta chain (IL-2R beta) did not appear on leukemic cells from any of
      the cases tested. AML cases expressing CD7 or HLA-DR antigen could induce IL-2R
      alpha more frequently than any other type of AML. Among interleukin-3 (IL-3),
      granulocyte-macrophage colony stimulating factor (GM-CSF) and G-CSF, IL-3 showed
      a more prominent effect on DNA synthesis in IL-2R alpha inducible cases than in
      its uninducible cases. These results suggest that IL-2R alpha but not IL-2R beta
      was easily inducible on AML cells with immature characteristics.

PMID- 7513372
TI  - Expression of functional Fas antigen on adult T-cell leukemia.
AB  - The expression of Fas antigen was analyzed in the peripheral blood mononuclear
      cells of 12 patients with adult T-cell leukemia (ATL) by flow cytometry. The
      induction of apoptosis in these cells by adding an anti-Fas antibody and the
      expression of activated T-cell surface antigens, CD25 and CD26, were also
      studied. It appears that the cells in ATL expressed a significantly larger number
      of Fas antigens than those in normal subjects (p < 0.01) and their fluorescent
      intensity was also shown to be much stronger in ATL (p < 0.01). The large number
      of ATL cells showed apoptosis in a short-term culture in the presence of the anti
      Fas antibody. There was no difference in the expression of Fas antigen among ATL
      cells with different phenotypes of CD4+/CD8-, CD4-/CD8- and CD4+/CD8+ as well as
      with clinical subtypes of ATL. Interestingly, the expression of Fas and CD26
      antigens showed a negative correlation (p < 0.01, r = 0.78). The strong
      expression of functional Fas antigen in ATL leads to the impression that anti-Fas
      antibody could be one of the treatment modalities for ATL which is known to be a
      very difficult disease to cope with.

PMID- 7513373
TI  - Malignant pheochromocytoma masquerading as acute pancreatitis--a rare but
      potentially lethal occurrence.
AB  - Pheochromocytoma mimicking acute pancreatitis as its initial clinical
      manifestation is a known, albeit rare, phenomenon. Herein we describe a patient
      with this occurrence. A striking feature was pronounced hyperamylasemia, almost
      exclusively of the S-type. Our theory is that the pheochromocytoma caused a
      catecholamine-induced cardiomyopathy, which contributed to failure of the left
      ventricle; pulmonary edema and release of S-type amylase from hypoxic lung tissue
      occurred subsequently.

PMID- 7513374
TI  - Use of orally administered opioids for cancer-related pain.
AB  - OBJECTIVE: To summarize the important principles of opioid analgesia for cancer
      related pain. DESIGN: We reviewed our personal experience and reports in the
      literature to characterize commonly prescribed high-potency opioids and their
      relative efficacy. MATERIAL AND METHODS: The pharmacologic features of various
      opioids, selection of appropriate agents, titration of doses, routes of
      administration, conversions between drugs, and management of side effects are
      discussed. RESULTS: In general, the oral route is preferred because of ease of
      administration and good oral bioavailability of most opioids. In addition to the
      scheduled dosage of an opioid, extra "rescue" doses (5 to 10% of the total daily
      opioid dosage) should be available to the patient for breakthrough pain. Morphine
      is the prototype strong opioid against which other drugs are compared. Common
      adverse effects of opioids are sedation, nausea, constipation, respiratory
      depression, and myoclonus. Although no "standard" dose of opioid exists, the
      goals are to achieve adequate control of pain and to avoid major, unmanageable
      toxic effects. CONCLUSION: Pain is commonly associated with all stages of
      malignant disease. Despite its widespread occurrence, cancer pain is often
      inadequately managed because of poor assessment of pain and physicians'
      misconceptions about use of opioids. The cause of the pain should be carefully
      sought because it may yield important information about the underlying malignant
      disease. In most patients with moderate to severe cancer-related pain, oral
      administration of the appropriate opioid will achieve effective analgesia.

PMID- 7513375
TI  - Modulation of substance P-ergic system in the rat spinal cord by an opioid
      antagonist.
AB  - Substance P- and opioid peptide-immunoreactive nerve terminals functionally
      interact in the spinal cord as two opposing systems in the regulation of the
      nociceptive pathway. In order to determine how SP-ergic system adapts to chronic
      opioid receptor blockade, the effects of naltrexone on SP level, SP receptor and
      the second messenger system coupled to the SP receptor were examined in the rat
      spinal cord. Male Sprague-Dawley rats were treated with naltrexone or vehicle for
      seven days by constant minipump infusion. Animals were sacrificed on day 8,
      spinal cords rapidly removed, segmentally sectioned and used to determine SP and
      inositol 1,4,5-trisphosphate [ins(1,4,5)P3] tissue contents, and to examine the
      regulation of their respective receptors in in vitro receptor binding assays.
      Following chronic naltrexone treatment, SP content in the lumbosacral segment of
      the spinal cord was increased by 53% over matched control values. The binding
      capacity (Bmax) of SP receptors, determined using [125I]BHSP, in lumbosacral
      synaptosomal membranes was significantly increased by 92%, but the binding
      affinity (Kd) remained unchanged. In addition, the concentration of [Sar9,
      Met(O2)11]SP, an NK-1 receptor-specific agonist, required to inhibit half of
      [125I]BHSP binding (IC50) in lumbosacral synaptosomal membranes was significantly
      decreased, but the IC50s for SP, the endogenous ligand for the SP receptor, and
      [Pro7]NK B, an NK-3 receptor-specific agonist, were unaltered by chronic blockade
      of opioid receptors. The data suggest that although naltrexone does not directly
      interact with tachykinin receptors, it acts indirectly on SP-ergic neurons to
      cause a change in the apparent affinity of NK-1 receptor (as reflected by a
      change in IC50 value). Formation of cellular ins(1,4,5)P3 in the lumbosacral
      cord, quantified by a highly sensitive and selective radioreceptor assay, was
      significantly increased by 34% relative to matched controls. A time course study
      indicated that increases in ins(1,4,5)P3 contents over the time studied
      corresponded qualitatively with increases in SP level in the lumbosacral cord.
      With [3H]ins(1,4,5)P3 as a ligand, Scatchard analyses of the concentration
      dependent saturation curves showed that the density of intracellular ins(1,4,5)P3
      receptors was also increased by 119%, with no change in binding affinity. The
      data suggest that ins(1,4,5)P3 formation, possibly coupled to functional SP
      receptor activation, and ins(1,4,5)P3 receptors, which mediate ins(1,4,5)P3
      induced alterations in intracellular Ca2+ flux, are increased in the lumbosacral
      cord by chronic blockade of opioid receptors. Taken together, the data support
      the concept of a role for endogenous opioids in the regulation of SP receptor
      activity in the spinal cord.

PMID- 7513377
TI  - How far should we investigate and treat prostate cancer? A lawyer's perspective.

PMID- 7513376
TI  - Persistent AMPA receptor stimulation alters [Ca2+]i homeostasis in cultures of
      embryonic dopaminergic neurons.
AB  - The effect of the ionotropic glutamate receptor agonist, AMPA, on intracellular
      Ca2+ concentrations ([Ca2+]i) was studied in dopaminergic neurons present in
      primary cultures of ventral tegmental mesencephalon of 14 day rat embryos.
      Exposure of cells to 10 microM AMPA for 1 min increased [Ca2+]i by 2-3 fold in
      dopaminergic and other neurons and this response was obliterated within 5 min by
      superfusion with AMPA-free incubation buffer. In dopaminergic neurons, 1 min or 5
      min exposure to 50 microM AMPA increased [Ca2+]i 3 to 5 times over control
      values. This rise in [Ca2+]i persisted even after a 20 min superfusion with AMPA
      free media, whereas, [Ca2+]i in non-dopaminergic neurons was reversed to control
      values during this time. Preincubation (2 min) of cultured cells with NBQX or the
      L-type channel blocker, nifedipine, but not with MK-801 blunted the rise of
      [Ca2+]i in dopaminergic and other neurons. Pretreatment with 2 microM NBQX
      shifted the dose response curve for AMPA to the right without changing the basal
      [Ca2+]i. The presence of 10 microM dantrolene, a blocker of Ca2+ release from
      intracellular stores, did not alter the initial rise of [Ca2+]i elicited by 50
      microM AMPA, but prevented the destabilization of Ca2+ homeostasis by
      facilitating the recovery to normal of basal [Ca2+]i. Exposure to 50 microM AMPA
      (5 min) caused an irreversible increase of [Ca2+]i in dopaminergic neurons and
      cell death was manifested by propidium iodide uptake 6-7 h after AMPA
      exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513379
TI  - PSA syndrome.

PMID- 7513378
TI  - [The role of oxytalan fibers in the stomatognathic system. A bibliographic
      review].
AB  - The authors review the oxytalan fibers, that belong to the elastic system fibers
      of the connective tissue. They are observed in many structures of the
      stomatognathic system, particularly in the periodontal ligament and TMJ disc.

PMID- 7513380
TI  - Trifluoperazine and calmidazolium have multiple actions on the release of
      noradrenaline from sympathetic nerves of mouse atria.
AB  - The aim of this study was to determine whether the calmodulin inhibitors
      trifluoperazine (TFP) and calmidazolium (CMZ) could decrease the action-potential
      evoked release of noradrenaline from mouse isolated atria incubated with [3H]
      noradrenaline in support of the hypothesis that calmodulin is involved in
      neurotransmitter release. TFP (10 microM and 30 microM) significantly enhanced
      stimulation-induced (S-I) outflow of radioactivity from mouse atria but had no
      effect at 1.0 microM or 70 microM. TFP (70 microM) also significantly increased
      the spontaneous outflow of radioactivity. The facilitatory effect of TFP (10
      microM) on S-I outflow of radioactivity persisted in either the presence of 3
      isobutyl-1-methylxanthine (100 microM) or atropine (0.3 microM) indicating that
      this effect of TFP was not mediated through either inhibition of
      phosphodiesterases or through interference with presynaptic muscarinic receptors,
      respectively. In the presence of phentolamine, the facilitatory effect of TFP (10
      microM) on S-I outflow was reduced but there was no effect on S-I outflow at 70
      microM. However, in the presence of a combination of both phentolamine (1.0
      microM) and the neuronal uptake blocker desipramine (1.0 microM) a significant
      inhibitory effect of TFP (70 microM) on the S-I outflow of radioactivity was
      observed, indicating that effects of TFP on presynaptic alpha-adrenoceptors and
      neuronal uptake had disguised an inhibitory effect on S-I noradrenaline release.
      Another inhibitor of the Ca(2+)-calmodulin complex, calmidazolium (CMZ, 10
      microM) inhibited the S-I outflow of radioactivity but had no effect at 1.0
      microM. However, CMZ (10 microM) also induced a concomitant increase in the
      spontaneous outflow of radioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513381
TI  - Comparison of the effects of eleven histamine H1-receptor antagonists on
      monoamine turnover in the mouse brain.
AB  - To compare in vivo effects of eleven compounds of different classes of histamine
      H1-receptor antagonists (alcoholamines: diphenhydramine, carbinoxamine, and
      clemastine; ethylenediamines: mepyramine, tripelennamine, and clemizole;
      alkylamines: triprolidine and chlorpheniramine; piperazines: meclizine and
      homochlorcyclizine; phenothiazines: promethazine) on neuronal uptake of dopamine
      (DA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT), the effects on the
      turnover of these monoamines were examined in the mouse brain, based on the alpha
      methyl-p-tyrosine-induced depletion of DA and NA or probenecid-induced
      accumulation of 5-hydroxyindoleacetic acid. The DA turnover was reduced
      remarkably by diphenhydramine, tripelennamine, and promethazine, and also
      significantly by chlorpheniramine, mepyramine, clemizole, and homochlorcyclizine,
      at doses used in the ordinary animal experiments. The 5-HT turnover was reduced
      markedly by mepyramine, tripelennamine, and chlorpheniramine. In contrast, the NA
      turnover was increased by promethazine and homochlorcyclizine, possibly due to
      their antagonistic effects on alpha-adrenoceptors. These results suggest that (1)
      the degree of inhibition of the uptake of DA and 5-HT by histamine H1-receptor
      antagonists is considerably different, (2) most H1-antagonists have little
      influence on NA uptake and some compounds enhance NA release, and that (3)
      carbinoxamine, clemastine, triprolidine, and meclizine have comparatively weak
      influences on monoamine metabolism. These effects on brain monoamine systems may
      be related to some central actions of histamine H1-receptor antagonists, such as
      an addiction to these compounds combined with opioids.

PMID- 7513382
TI  - The basal and stimulated release of the endothelium-derived relaxing factor from
      isolated pig coronary arteries does not interfere with the vascular release of
      superoxide.
AB  - Oxygen-derived free radicals, in particular superoxide anions, are known to
      inactivate the endogenous vasodilator endothelium-derived relaxing factor (EDRF)
      which is probably identical with the gaseous radical nitric oxide. It is possible
      that EDRF is not the target of superoxide anions but may also be an endogenous
      scavenger of this radical. Superoxide anions generated by the vessel wall were
      measured by a modified lucigenin-enhanced chemiluminescence technique in isolated
      pig coronary artery rings with intact endothelium. The addition of bovine
      superoxide dismutase, a scavenger of superoxide anions, decreased the
      chemiluminescence signal by 40 +/- 26% (mean +/- SD; P < 0.05; n = 21) indicating
      reduced generation/release of superoxide anions. In contrast, pretreatment of
      coronary artery rings with diethyldithiocarbamate, an inhibitor of the intrinsic
      copper-zinc superoxide dismutase, increased the chemiluminescence response by 136
      +/- 128% (P < 0.05; n = 21). This increase in the chemiluminescence response
      induced by diethyldithiocarbamate-pretreatment was almost abolished in the
      presence of added bovine superoxide dismutase. Specific inhibition of the EDRF
      release with nitro-L-arginine (100 microM) did not affect the chemiluminescence
      response. On the other hand, stimulation of the EDRF release by substance P (10
      nM) or addition of the endothelium-mediated relaxant bradykinin (0.1 microM) did
      not affect the chemiluminescence response. Stimulation of the EDRF release with
      serotonin (0.1 microM) significantly reduced the photon emission by 15 +/- 16% (n
      = 27).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513383
TI  - Vasoactive intestinal peptide suppresses neuronal cell death induced by nerve
      growth factor deprivation in rat sympathetic ganglion cells in vitro.
AB  - Neuropeptides were examined for their effects on the survival of cultured rat
      superior cervical ganglion cells after acute deprivation of nerve growth factor
      (NGF). Vasoactive intestinal peptide (VIP, 3 microM) delayed the neuronal death
      about 6 h alone. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.2
      mM) greatly potentiated its effect, reducing EC50 from 2.5 microM to 8 nM. The
      neuronal death was completely suppressed under this condition. On the other hand,
      substance P (1-100 microM) or enkephalin (1-100 microM) alone did not modify the
      death, whereas the latter (100 microM) enhanced the survival-promoting effect of
      membrane depolarization with elevated K+. These results suggest strongly that
      neuropeptides regulate the NGF-independent survival of sympathetic neurons
      through a cAMP-dependent mechanism.

PMID- 7513384
TI  - N omega-nitro-L-arginine inhibits vasodilations and elevations of both cyclic AMP
      and cyclic GMP levels in rat aorta induced by calcitonin gene-related peptide
      (CGRP).
AB  - Our previous studies showed that vasodilations and elevations of both cyclic AMP
      and cyclic GMP levels in rat aorta induced by rat calcitonin gene-related peptide
      (rCGRP) are inhibited by hemoglobin and methylene blue, blockers of the
      endothelium-derived relaxant factor (EDRF, now recognized as nitric oxide [NO]).
      In the present study, we used N omega-nitro-L-arginine (L-NNA), a selective
      inhibitor of nitric oxide synthase, to test whether rCGRP-induced relaxations and
      cyclic AMP and cyclic GMP responses in rat aorta require de novo synthesis of NO.
      L-NNA (30 microM, 15 min) inhibited by 84, 76 and 73% the relaxations induced by
      rCGRP at 1, 10 and 100 nM, respectively. D-NNA (30 microM), which does not
      inhibit nitric oxide synthase, did not block rCGRP-induced vasorelaxations.
      Addition of L-arginine (3 mM) 5 min before L-NNA completely prevented the L-NNA
      inhibition of CGRP-induced relaxations. L-NNA (30 microM, 15 min) also inhibited
      the elevations of both cyclic AMP and cyclic GMP levels caused by CGRP (100 nM).
      The data suggest that de novo synthesis of nitric oxide from its precursor L
      arginine is required for rCGRP to induce vasodilations and elevations of both
      cyclic AMP and cyclic GMP levels in rat aorta.

PMID- 7513385
TI  - After transduction: response shaping and control of transmission by ion channels
      of the photoreceptor inner segments.
AB  - Photoreceptors convert the elements of the visual image into the elements of a
      neural image. This process involves well-studied molecular events occurring at
      the outer segment, but also employs important molecular events in the proximal
      regions of the photoreceptor, including the synaptic terminal, encompassed here
      as the inner segment. Integral to neural processing at this level in the visual
      system, the inner segment mechanisms modify the visual signal before transmission
      to second order cells at the photoreceptor output synapse. This commentary,
      emphasizing the author's own work, discusses biophysical properties of the
      ensemble of ion channels in the photoreceptor inner segment that shape the light
      response and enable its transmission. Examples that illustrate ion channels whose
      biophysical properties seem well suited for their roles in photoreceptor function
      include: h channels, cation-selective channels activated by hyperpolarization,
      which carry current that counteracts the strong hyperpolarizing influence of cGMP
      gated channel closure accompanying bright light; Kx channels, carrying potassium
      current which shares the kinetic properties of the M-current found in many other
      cell types, which shape responses to dim light and set the dark resting
      potential; and Ca channels that regulate calcium influx to control Ca-gated
      channel activity and synaptic output, "re-transducing" the neural signal now into
      a chemical one. The role of chloride current, carried in Ca-activated Cl channels
      dependent on the unknown chloride equilibrium potential in photoreceptors, is
      also discussed.

PMID- 7513387
TI  - Brief increases in intracellular Ca2+ activate K+ current and non-selective
      cation current in rat nucleus basalis neurons.
AB  - Neurons were acutely dissociated from the rat nucleus basalis, and membrane
      currents (whole-cell patch-clamp) and intracellular free Ca2+ concentrations
      (Fura-2) were measured simultaneously from large neurons (approximately 25
      microns in diameter). A brief depolarization from -60 to 0 mV for 200 ms evoked
      an increase in intracellular free calcium and a slow outward tail current (72 +/-
      8 pA, n = 30). The outward current reversed polarity at -75.5 +/- 2.7 mV (n =
      14). The tail current declined and the intracellular calcium recovered its
      resting level exponentially with time-constants of 1.0 +/- 0.1 s and 2.5 +/- 0.2
      s, respectively (n = 17). In neurons loaded with Cs-gluconate, a similar
      depolarizing pulse evoked a similar increase in intracellular free calcium, but
      this was now followed by an inward tail current (118 +/- 8 pA, n = 44). The
      inward tail current reversed polarity at -27.8 +/- 3.8 mV (n = 7), and was
      suppressed by removal of external sodium ions. Neither outward nor inward tail
      currents were observed, when the external solution was calcium-free or when the
      pipette solution contained EGTA (10 mM). These results indicate that a
      depolarization causes a calcium entry and that this consequently increases both
      K+ conductance and non-selective cation conductance.

PMID- 7513388
TI  - Trigeminal projections to the peribrachial region in the muskrat.
AB  - The anterograde and retrograde transport of wheat germ agglutinin-horseradish
      peroxidase was used to study the trigeminoperibrachial pathway in the muskrat
      after injections of tracer into either the medullary dorsal horn or the
      dorsolateral pons. After injections into the medullary dorsal horn, labeled
      fibers ascended into the ipsilateral dorsolateral pons via the spinal trigeminal
      tract, within the neuropil of the trigeminal sensory complex and within the
      reticular formation adjacent to the spinal trigeminal nucleus. At caudal levels
      of the ipsilateral peribrachial area, dense terminal-like label distributed in
      the Kolliker-Fuse nucleus continued into the lateral parabrachial nucleus. At
      intermediate levels ipsilaterally, the Kolliker-Fuse nucleus again was labeled
      densely, as were areas analogous to the external lateral and external medial
      subnuclei of the parabrachial nucleus in the rat. A thin band of label along the
      ventral spinocerebellar tract outlined an unlabeled area in the central portion
      of the lateral parabrachial nucleus. Rostrally near the pontomesencephalic
      junction, the area designated the superior lateral subnucleus in the hamster was
      labeled, while sparser label was present more dorsally. Contralateral to the
      injections, caudal and intermediate levels of the peribrachial area contained
      only scant reaction product. However, the rostral area of the superior lateral
      subnucleus was labeled densely via fibers ascending in the trigeminothalamic
      tract. Injections made just rostral to the obex and either centered in or
      including the dorsal or ventral paratrigeminal nuclei produced similar labeling
      at caudal and intermediate levels of the peribrachial area. An exception,
      however, was that the caudal medial parabrachial nucleus was also labeled after
      the dorsal paratrigeminal injection. Also, only scant label was found in the
      rostral third of the dorsolateral pons on either side after these injections.
      Both trigeminothalamic and trigeminolemniscal pathways were labeled
      contralaterally after these injections. These trigeminal projections to the
      dorsolateral pons were compared to the projections from the nucleus tractus
      solitarii and the ventrolateral medulla. Numerous trigeminal neurons were labeled
      retrogradely after injections of wheat germ agglutinin-horseradish peroxidase
      into the dorsolateral pons. In the medullary dorsal horn, they were found almost
      exclusively in laminae I and V. Labeled neurons in lamina I were especially
      prominent in rostral ventral levels of the medullary dorsal horn. Labeled cells
      in lamina I were continuous with others found in the displaced band of substantia
      gelatinosa at the interface of the subnucleus caudalis and subnucleus
      interpolaris, as well as with those found in the ventral and dorsal
      paratrigeminal nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7513386
TI  - Serotonin2 receptor-mediated excitation of interneurons in piriform cortex:
      antagonism by atypical antipsychotic drugs.
AB  - Rat piriform cortex contains a subpopulation of presumed GABAergic interneurons
      located near the border of layers 2 and 3 that express excitatory serotonin2
      receptors. These serotonin2-responsive interneurons send axons to layer 2
      pyramidal cells. Using an in vitro brain slice preparation, serotonin2 receptor
      mediated excitation can be assessed either by directly recording from the
      interneurons or by recording the increase in inhibitory postsynaptic potentials
      in the pyramidal cells. Intracellular recordings from the interneurons
      demonstrated that compared to pyramidal cells they had a more depolarized resting
      membrane potential, a higher input resistance and shorter action potential
      duration. The serotonin2 receptor-mediated excitation was associated with a
      strong depolarization (range 3-22 mV). We found that the atypical antipsychotic
      drugs, risperidone and clozapine, which have relatively high affinity for
      serotonin2 receptors, each dose-dependently inhibited the serotonin2-mediated
      excitation of the interneurons with IC50 values of 7 nM and 1.4 microM,
      respectively. This antagonism was specific to the extent that excitation mediated
      by agonists at excitatory amino acid receptors were not blocked at concentrations
      of risperidone and clozapine that completely antagonized the serotonin2 receptor
      mediated excitation. The typical antipsychotic drug, chlorpromazine, inhibited
      the serotonin2-mediated excitation of the interneurons with an IC50 of 14 microM.
      Haloperidol, another typical antipsychotic drug, decreased the serotonin2
      response to about half of baseline at a concentration of 10 microM (the exact
      IC50 could not be calculated because higher concentrations produced non-specific
      effects on cells). Both risperidone and clozapine blocked the serotonin-elicited
      inhibitory postsynaptic potentials in layer 2 pyramidal cells at concentrations
      that approximated the IC50 for antagonizing the serotonin2-mediated excitation of
      the interneurons. Chlorpromazine and haloperidol, in the concentration range that
      blocked serotonin2 receptor-mediated excitation of interneurons, also blocked the
      serotonin-elicited inhibitory postsynaptic potentials in the pyramidal cells. The
      IC50 values for risperidone and clozapine, but not for chlorpromazine or
      haloperidol, for blocking serotonin2 receptor-mediated actions in rodent piriform
      cortical slice are in the range of the plasma concentrations of the drug that are
      clinically efficacious. Our data suggest that a potential site of action of the
      atypical antipsychotic drugs risperidone and clozapine could be antagonism of
      serotonin acting through serotonin2 receptors on GABAergic interneurons in
      cerebral cortex.

PMID- 7513389
TI  - Cholinergic neurons in the ventral trapezoid nucleus project to the cochlear
      nuclei in the rat.
AB  - A combination of retrograde axonal tract tracing and choline acetyltransferase
      immunocytochemistry was used to determine the cells of origin of the cholinergic
      innervation of the rat cochlear nucleus. The results showed that the cochlear
      nucleus receives a major cholinergic input from a group of small cells found in
      the ventral trapezoid nucleus. Experiments using an anterograde tracer confirmed
      the presence of a neuronal pathway from the ventral trapezoid nucleus to the
      cochlear nucleus and showed that this pathway travels via the trapezoid body.

PMID- 7513390
TI  - The relationship of efferent projections from the area postrema to vagal motor
      and brain stem catecholamine-containing cell groups: an axonal transport and
      immunohistochemical study in the rat.
AB  - The area postrema has been implicated as a major station for the processing of
      visceral sensory information, involved primarily in eliciting rapid homeostatic
      responses to fluid and nutrient imbalances. Yet the precise relationship of
      efferent projections from the area postrema to medullary motor and relay nuclei
      involved in such functions remains unclear. In this study, axonal transport and
      immunohistochemical techniques were used to investigate the relationship of
      efferent projections from the area postrema to vagal motor neurons and medullary
      catecholamine-containing cell groups in the rat. The results may be summarized as
      follows: (1) The area postrema gives rise to dense inputs to the commissural and
      medial parts of the nucleus of the solitary tract. Many of these projections are
      intimately associated with catecholamine-containing neurons in the A2 and C2 cell
      groups, including a particularly prominent input to a caudally placed cluster of
      adrenergic neurons (the C2d cell group) in the dorsal aspect of the medial part
      of the nucleus of the solitary tract. (2) The area postrema provides a dense
      input to the external lateral part of the parabrachial nucleus. (3) The area
      postrema does not project significantly to vagal motor neurons in either the
      dorsal motor nucleus or the nucleus ambiguus, although the possibility for inputs
      to distal dendrites of dorsal vagal motor neurons cannot be excluded. (4) En
      route to the parabrachial nucleus, axons of area postrema neurons traverse the
      regions of the A1, C1 and A5 cell groups, although these fibers make few
      arborizations, suggesting little functional contact. Together, these results
      suggest that sensory information received by the area postrema is dispatched to a
      restricted set of neurons in the commissural, medial, and dorsal parts of the
      nucleus of the solitary tract, most probably including catecholamine-containing
      cells in the A2, C2, and C2d cell groups, and to the external lateral portion of
      the parabrachial nucleus. The targets of area postrema projections are, in turn,
      in a position to effect adaptive changes in the activities of hypothalamic
      neurosecretory neurons, vagal motor neurons, and limbic forebrain regions in
      response to perturbations in fluid and nutrient homeostasis.

PMID- 7513391
TI  - Optic neuritis and multiple sclerosis: anti-MBP and anti-MBP peptide antibody
      secreting cells are accumulated in CSF.
AB  - Monosymptomatic unilateral optic neuritis (ON) is a common first manifestation of
      multiple sclerosis (MS) in which increased numbers of autoimmune T and B cells,
      recognizing different myelin autoantigens including myelin basic protein (MBP)
      and its peptides, have been implicated in a hypothetical immunopathogenesis.
      Using an immunospot assay to detect specific antibodies secreted by individual
      cells, we analyzed the B-cell repertoire to MBP and its amino acid residues 1-20,
      63-88, 110-128, and 148-165 in blood and CSF from patients with ON and MS, and
      from controls. There were cells secreting IgG antibodies to MBP and the four
      peptides in blood at mean numbers of 0.9 to 4.6 per 10(5) mononuclear cells,
      without differences between the three patient groups. Mostly, more than 100-fold
      more B cells with these specificites per 10(5) cells were found in CSF from the
      patients with ON and MS, without differences between these two groups but with
      many fewer in CSF from controls. None of the four included MBP peptides
      represented an immunodominant B-cell epitope in either ON or MS, and the B-cell
      response was not more restricted in ON than in MS. The autonomy of the autoimmune
      B-cell response in CSF was further supported by the pronounced asynchrony of the
      repertoire to the four MBP peptides in CSF compared with blood in individual
      patients. The large numbers of MBP- and MBP peptide-reactive B cells in CSF in
      early MS, as manifested by ON, could play a major role in the immunopathogenesis
      and perpetuation of MS. Alternatively, they could represent myelin breakdown or
      restoration.

PMID- 7513392
TI  - [Treatment methods for malfunctioning endoprostheses].
AB  - A survey on treatment options for salvation of malfunctions of biliary
      endoprostheses is given. If the anatomical situation makes it feasible the
      endoscopic procedure should be preferred which is less cumbersome to the patient.
      Percutaneous interventions may include procedures from the mechanical unclogging
      of the lumen to the removal and changing of the occluded endoprosthesis. The
      authors emphasize the advantages of the endoprostheses over the external-internal
      drainage even if interventionalists should count on even multiple changing of
      endoprostheses due to their tendency to occlusion in patients with a tumor
      ensuring relative long life expectancy.

PMID- 7513393
TI  - [The cytological picture in pleural pneumocystosis].
AB  - We report a case of a HIV+ patient treated with prophylactic aerosolized
      pentamidine. The patient showed evidence of tensive right pneumothorax and slight
      pleural effusion. The pleural fluid was aspired from the drainage and processed
      in our laboratory. The cytologic examination of aspired fluid revealed abundant
      Pneumocystis carinii organisms. The cytologic presentation is peculiar in pleural
      fluid because of the presence of a large amount of trophozoites and a small
      number of cysts. Direct examination and Giemsa stain are suitable methods to
      detect trophozoites. The diagnosis can be confirmed by Gomori and Toloidine Blu
      stains that demonstrate the presence of isolated and scarce cysts. Pneumocystis
      carinii can also be recognized in Papanicolaou-stained smears as eosinophilic
      aggregates.

PMID- 7513394
TI  - Extra-axial chordoma. Report of a case with immunohistochemical study.
AB  - A case of extra-axial chordoma arisen in the soft tissues of the posterior
      thoracic wall is reported. Immunohistochemistry showed coexpression of low
      molecular weight keratins, vimentin and S-100 protein in neoplastic cells.
      Although rare, examples of chordomas developing in extra-axial locations are
      reported in the literature and need be differentiated from other tumors that can
      mimic their histopathological features, such as myxoid chondrosarcomas.

PMID- 7513395
TI  - Patient advocate versus societal gatekeeper and the future of high-tech medicine.

PMID- 7513396
TI  - Performance of a 3.2-mm to 6-mm adaptor.
AB  - A study was undertaken to evaluate the performance of a 366-08 adaptor that
      adapts an in-line bipolar 3.2-mm connector to a 6-mm pulse generator connector. A
      total of 14 adaptors were implanted in individual patients. Eight of the 14
      adaptors failed, an additional failure is probable. The average follow-up time
      was 32.1 months. The most likely cause of failure was the spring-loaded mechanism
      of the adaptor, which fatigues with time. All eight of the documented failures
      presented with loss of capture and were accompanied by increased measured lead
      impedances. In addition, some failed systems demonstrated loss of sensing. As a
      result, prophylactic replacement of ventricular lead systems incorporating this
      adaptor would be advisable. Otherwise, more frequent monitoring with lead
      impedance measurements may suffice.

PMID- 7513397
TI  - Comparative thrombogenicity of pacemaker leads.
AB  - To evaluate the thrombogenicity of transvenous silicone and polyurethane
      pacemaker leads, 9 of 12 anesthetized Yorkshire pigs (27-32 kg) were implanted
      with silicone (n = 5) or polyurethane (n = 4) pacemaker leads via a femoral vein.
      The remaining three pigs served as controls. All 12 pigs were injected with
      autologous indium-111 labeled platelets (300-420 muCi) 24 hours before anesthesia
      induction. The pigs were monitored for 3 hours under a gamma camera.
      Radioactivity in blood and lead segments was measured with a gamma counter.
      Platelet deposits were denser on silicone leads (441.58 +/- 915.0 to 2.19 +/-
      2.07) than on polyurethane leads (1.21 +/- 1.33 to 0.27 +/- 0.14) (P > 0.05).
      Denser platelet deposits were detected at the tip of all leads. Density of
      platelet deposits declined from tip to distal segments in silicone leads. The
      percentage of injected platelet radioactivity in the lungs of pigs with either
      silastic leads (12.9 +/- 2.3%) of polyurethane leads (10.1 +/- 2.2%) was higher
      than in the controls (4.6 +/- 0.5%) (P < 0.05). This difference indicates
      thrombus formation and embolization in the lungs early after lead implantation.
      Thrombogenicity of polyurethane leads may be lower than that of silicone leads.

PMID- 7513398
TI  - Effect of low dose aspirin on augmented plasminogen activator inhibitor type 1
      activity in patients with permanent pacemakers.
AB  - To clarify the activity states of coagulation and fibrinolysis in patients with a
      permanent pacemaker, we studied 29 patients more than 4 months after operation.
      They were divided into a single pacemaker lead group (S, n = 14) and a double
      lead group (D, n = 15). Prothrombin time, activated partial thromboplastin time,
      fibrinogen, antithrombin III, tissue-type plasminogen activator (tPA) activity,
      plasminogen activator inhibitor type-1 (PAI-1) activity, and platelet aggregation
      were measured and compared to those in an age-matched control group (C, n = 7).
      The effects of low dose aspirin (81 mg/day) in the patients (n = 21) were also
      studied 2 weeks after administration. PAI-1 activity in groups S and D was
      significantly higher than that in the group C (53.5 +/- 36.5, 86.8 +/- 59.2 ng/mL
      vs 19.4 +/- 7.2 ng/mL; P < 0.01 and P < 0.005). Platelet aggregation induced by
      collagen was slightly higher in groups S and D than group C. Other parameters
      were not significantly different. In the patients, low dose aspirin significantly
      suppressed collagen induced platelet aggregation (71.8 +/- 20.3% vs 41.7 +/-
      28.3%; P < 0.005), but not PAI-1 activity. tPA activity was increased
      significantly by the low dose aspirin administration (3.94 +/- 1.85 ng/mL vs 2.48
      +/- 1.19 ng/mL; P < 0.005). Thus, PAI-1 activity in patients with a permanent
      pacemaker is elevated, and the activity is not suppressed by low dose aspirin
      unlike the platelet aggregation.

PMID- 7513399
TI  - Effect of beta-adrenergic stimulation on the QT interval of children with
      syncope.
AB  - The effect of intravenous bolus doses (0.25, 0.5, 1.0 microgram) of isoproterenol
      on the QT and RR intervals was reviewed in a group of 34 children undergoing
      autonomic testing for syncope. Twenty-one patients had a positive orthostatic
      test and 13 were negative. The two groups (positive and negative) were compared.
      Baseline QT and RR intervals were similar. The RR interval was shortened by
      isoproterenol in both groups. Isoproterenol shortened the QT interval in the
      negative group (as seen in normal persons), but produced QT prolongation in the
      positive group, although neither reached statistical significance when compared
      to baseline within the respective group. Comparing the values for RR and QT at
      each dose of isoproterenol (including baseline) between the two groups showed a
      significant difference in the QT interval after the 1.0-microgram dose of
      isoproterenol. Thus children with orthostatic positive neurocardiogenic syncope
      showed a different QT response to beta-adrenergic stimulation. This lends support
      to the theory of altered beta-adrenergic sensitivity being present in children
      with neurocardiogenic syncope.

PMID- 7513400
TI  - Late potentials are unaffected by radiofrequency catheter ablation in patients
      with ventricular tachycardia.
AB  - Reentrant ventricular tachycardia is dependent on an area of myofibers, embedded
      in scar tissue, which exhibit slow conduction. Late potentials recorded by signal
      averaged electrocardiography appear to correspond to these zones of slow
      conduction and frequently are present in patients with VT. We hypothesized that
      elimination of inducible VT by catheter-mediated ablation of critical areas of
      slow conduction would alter late potentials. Four patients underwent catheter
      ablation in which radiofrequency current was delivered to zones of slow
      conduction exhibiting isolated mid-diastolic potentials that could not be
      dissociated from the tachycardia. The four patients had developed VT (cycle
      length 382 +/- 50 msec; mean +/- SEM) 13-180 months after inferior myocardial
      infarction. Late potentials were present in each patient before catheter ablation
      was attempted. Although VT was not inducible in any patient immediately after
      ablation, late potentials were still present in all four patients and there was
      no significant difference in the QRS duration (136.5 +/- 4.0 msec postablation;
      135.7 +/- 4.5 msec preablation), root mean square voltage in the terminal 40 msec
      of the QRS (10.0 +/- 1.0 microV postablation; 5.9 +/- 0.4 microV preablation), or
      in the duration of the low amplitude signal (69.2 +/- 2.0 msec postablation; 62.7
      +/- 3.4 msec preablation). At follow-up electrophysiology study performed 14 +/-
      7 days after ablation, one of the four patients had inducible VT. In conclusion,
      late potentials persist even after successful radiofrequency catheter ablation
      and do not appear to be useful for predicting results of follow-up
      electrophysiology study.

PMID- 7513401
TI  - Signal-averaged electrocardiography in elderly subjects with and without heart
      disease.
AB  - Prevalence of abnormal signal-averaged electrocardiography in normal populations
      appears to be low, but has not been studied previously in an asymptomatic elderly
      population. To study the prevalence of abnormal ventricular late potentials in an
      elderly population, a group of 51 subjects with no evidence of cardiac disease
      and ranging in age from 62 to 102 years underwent signal-averaged
      electrocardiography. Results were compared to a group of 179 patients similar in
      age but with complex ventricular arrhythmias, and to a group of 25 asymptomatic
      volunteers under the age of 50. The prevalence of an abnormal signal-averaged ECG
      was 14% in the normal elderly subjects, and 31% in the patients (P = 0.01), and
      4% in the young subjects (P = NS). We conclude that the prevalence of abnormal
      ventricular late potentials in elderly patients without heart disease is similar
      to levels reported in other populations of normal controls, but elderly patients
      with cardiac disease have a significantly higher prevalence of abnormal signal
      averaged ECG studies than the normals.

PMID- 7513402
TI  - Demonstration of entrainment and presence of slow conduction during ventricular
      tachycardia in arrhythmogenic right ventricular dysplasia.
AB  - During VT in two cases with arrhythmogenic right ventricular dysplasia,
      entrainment criteria, constant fusion beats except for the last entrainment beat,
      progressive fusion, and a localized conduction block associated with interruption
      of VT, were demonstrated with rapid ventricular pacing performed during VT.
      Furthermore, a long conduction interval was present during entrainment from the
      pacing site to the earliest activation site during VT, indicating the presence of
      a slow conduction area. VT in these cases was, thus, due to reentry with an area
      of slow conduction within the circuit.

PMID- 7513403
TI  - Comparison of ventricular function in atrial rate adaptive versus dual chamber
      rate adaptive pacing during exercise.
AB  - The hemodynamic effects of two different pacing modes--rate adaptive atrial
      (AAIR) versus dual chamber (DDDR) pacing--were assessed in 12 patients with DDDR
      pacemakers during upright bicycle exercise first-pass radionuclide angiography
      using a multiwire gamma camera with tantalum-178 as a tracer. All patients had
      sinus node disease with intact AV conduction. Patients exercised to the same
      heart rate in random order in these two different pacing modes, AAIR and DDDR
      with AV delay (of 100 msec) selected to maintain 100% ventricular capture.
      Cardiac output increased significantly above baseline values during exercise in
      both pacing modes: 154 +/- 41% (mean +/- SEM, P = 0.002) with AAIR, versus 95 +/-
      24% (P = 0.004) with DDDR (P = NS between the two modes). The peak filling rate,
      likewise, increased in both pacing modes (2.3 +/- 0.21 end-diastolic volumes/sec
      to 3.8 +/- 0.31 end-diastolic volumes/sec in AAIR [P = 0.0004] and 2.2 +/- 0.18
      end-diastolic volumes/sec to 3.4 +/- 0.27 end-diastolic volumes/sec in DDDR [P =
      0.0008]). LV ejection fraction was normal at rest (60 +/- 4%, SEM) and did not
      significantly change with submaximal exercise in either pacing mode (both 56%, P
      = NS). No significant changes in end-diastolic volume or stroke volume indexes
      occurred with exercise in either pacing mode. Our study demonstrates that in
      patients with normal resting LV function, AAIR and DDDR pacing are equally
      effective in attaining appropriate increases in cardiac output and LV filling
      during exercise.

PMID- 7513405
TI  - Alteration of the QT/RR relationship in patients with idiopathic ventricular
      tachycardia.
AB  - It has been shown that alterations in QT/RR relationship may be associated
      arrhythmogenesis in several clinical settings. In the present study the QT/RR
      relationship was studied in 20 patients with idiopathic ventricular tachycardia
      (12 men and 8 women, aged 41 +/- 14 years) compared to 20 normal subjects (9 men
      and 11 women, aged 39 +/- 13 years). All the patients were off any antiarrhythmic
      drugs and had no evidence of intraventricular conduction defects. The QT
      intervals and their preceding RR intervals were measured on electrocardiogram
      strips from 24-hour Holter tapes at hourly intervals. The differences in the
      maximum, minimum, and mean of either the QT interval or its corrected values
      between patients with idiopathic ventricular tachycardia and normal subjects were
      not statistically significant. There was a significant correlation between the QT
      and RR intervals in normal subjects (gamma = 0.73 +/- 0.12, P < 0.05) and in
      patients with idiopathic ventricular tachycardia (gamma = 0.80 +/- 0.10, P <
      0.05). However, the linear regression line of the QT interval against the RR
      interval were significantly (P < 0.001) altered in patients with idiopathic
      ventricular tachycardia (QT = 0.24 +/- 0.18 RR) compared to normal subjects (QT =
      0.27 +/- 0.12 RR). We conclude that although there is no significant change in
      the QT interval and its corrected values, the QT/RR relationship is significantly
      altered in patients with idiopathic ventricular tachycardia as compared to normal
      subjects. This may be of importance in the pathogenesis of idiopathic ventricular
      tachycardia in these patients.

PMID- 7513404
TI  - Unipolar electrogram models for prediction of outcome in radiofrequency ablation
      of accessory pathways.
AB  - Meticulous catheter positioning close to the accessory pathway is essential for
      successful radiofrequency ablation. The aim of this study was to identify local
      unipolar electrogram characteristics predictive of radiofrequency ablation
      outcome, enabling more accurate accessory pathway localization and catheter
      positioning. So far mainly bipolar electrogram parameters have been evaluated,
      stressing the importance of the presence of an accessory pathway potential.
      However, especially in the absence of this parameter, the unipolar recording mode
      can be expected to hold several advantages. Nine local unipolar electrogram
      characteristics were analyzed in preexcited sinus rhythm directly preceding
      radiofrequency pulses in 35 consecutive patients with a manifest accessory
      atrioventricular pathway. A total of 1,230 unipolar electrogram complexes were
      analyzed and recorded at 138 ablation sites. Ablation was successful in 30/35
      patients (86%). Multivariate analysis provided two unipolar models for prediction
      of ablation outcome: in Model I, sites with a suspected accessory pathway
      potential, local AV interval < or = 30 msec and catheter stability had 76%
      probability of success, but no more than 1% in their absence. In contrast, using
      the bipolar recording mode, presence of a suspected accessory pathway potential
      was the only one of these parameters shown to differentiate between successful
      and unsuccessful sites, with a predicted chance of success of 48%. Model II, not
      requiring assessment of possible accessory pathway potentials, showed a 63%
      probability of success for the combination of initial positivity of the local
      ventricular signal < or = 0.1 mV, AV interval < or = 30 msec, and catheter
      stability, but no more than 7% in their absence. Moreover, gradual decrease of
      initial ventricular positivity and AV interval while approaching a subsequently
      successful site allows the use of these parameters as dynamic mapping tools.
      Local unipolar electrogram parameters may thus facilitate precise accessory
      pathway localization and catheter positioning while offering important
      information supplementary to the bipolar mode, and enable accurate prediction of
      ablation outcome at a given site also in the absence of accessory pathway
      potential recording.

PMID- 7513406
TI  - Effect of biphasic waveform pulse on endocardial defibrillation efficacy in
      humans.
AB  - Several clinical studies have proved increased defibrillation efficacy for
      implantable cardioverter defibrillators with biphasic pulse waveforms compared to
      monophasic pulse waveforms. This difference in defibrillation efficacy depends on
      the type of defibrillation lead system used. The influence of biphasic
      defibrillation pulse waveforms on the defibrillation efficacy of purely
      endocardial defibrillation lead systems has not yet been sufficiently examined,
      we, therefore studied 30 consecutive patients with drug refractory ventricular
      tachyarrhythmias during the implantation of a cardioverter defibrillator. After
      implanting an endocardial "integrated" sensing/defibrillation lead we performed a
      prospective randomized comparison of the defibrillation efficacy of monophasic
      and biphasic defibrillation waveform pulses. For endocardial defibrillation with
      the biphasic waveform the mean defibrillation threshold was 12.5 +/- 4.9 joules
      and for the monophasic waveform 22.2 +/- 5.6 joules (P < 0.0001). There was a
      decrease in the required defibrillation energy of biphasic defibrillation in
      29/30 patients. Thus considering purely endocardial defibrillation a
      statistically significant and clinically relevant increase in defibrillation
      efficacy can be demonstrated for biphasic defibrillation waveform pulses.

PMID- 7513407
TI  - The effect of overdrive pacing rate and duration on ventricular escape rhythms in
      patients with chronic complete atrioventricular block.
AB  - The effect of overdrive (OD) pacing rate and duration on subsidiary pacemakers
      was evaluated in 54 patients with third-degree AV block. They had a permanent
      pacemaker implanted 61 +/- 56 months earlier because of complete AV block in 38
      patients and, in 16 patients because of second-degree AV block, which in the
      interim advanced to complete AV block. The patients had a reliable infranodal
      escape rhythm, with a mean cycle length of 2,022 +/- 603 msec, upon
      discontinuation of the ventricular OD pacing, at a rate of 40 beats/min. The
      escape interval and escape rhythm cycle length was evaluated after OD pacing at
      40, 50, 60, 70, 90, and 100 beats/min for 30 seconds, at each rate. In 100% of
      the patients the subsidiary pacemaker recovered after OD pacing at 40 and 50
      beats/min and the number decreased to 59% at a rate of 100 beats/min. The escape
      interval prolonged gradually between OD pacing at 40 and 100 beats/min, by 56%.
      The effect of OD pacing duration at 50 and 70 beats/min was evaluated. At an OD
      pacing rate of 70 beats/min there was a significant effect of the pacing duration
      on the escape interval. There were significant differences in the escape interval
      duration and escape rhythm cycle length between males and females, patients with
      or without coronary artery disease, and patients with narrow or wide QRS escape.
      However, the increase in the OD pacing rate had a similar effect on the escape
      interval in the above mentioned groups. There was no effect on the paced QRS
      duration and sinus cycle length at each OD pacing rate.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7513409
TI  - Data protection and security.

PMID- 7513408
TI  - Why do some patients have high defibrillation thresholds at defibrillator
      implantation? Answers from basic research.
AB  - Implantable cardioverter defibrillators reduce the risk of sudden cardiac death
      in patients with ventricular tachyarrhythmias. However, for the few patients with
      unacceptably high defibrillation thresholds at implantation the risk of sudden
      death may remain high. If a small number of defibrillation attempts are used to
      determine a defibrillation threshold, then a high defibrillation threshold may
      occur in some patients due to the probabilistic nature of defibrillation: a small
      percentage of shocks will fail even at optimal shock strengths. Basic
      investigations have suggested mechanisms for high defibrillation thresholds in
      other patients. The extracellular potential gradients produced by a shock
      correlate with ability to defibrillate and may be used to classify mechanisms for
      high defibrillation thresholds. Computerized mapping studies have demonstrated
      that extracellular potential gradient fields produced by defibrillation shocks
      are uneven with high gradient areas close to the electrodes and low gradient
      areas distant from the electrodes. A high defibrillation threshold may occur
      because: (1) a shock creates a subthreshold potential gradient in the low
      gradient areas; (2) a patient has a higher minimum potential gradient threshold
      than other patients; or (3) a shock leads to refibrillation in the high gradient
      areas. This article reviews experimental evidence to support each of these three
      possibilities then suggests experimental and clinical investigations that may
      clarify the causes of high defibrillation thresholds in patients.

PMID- 7513410
TI  - Trends in subspecialty training in cardiac electrophysiology and pacing.

PMID- 7513411
TI  - Implantable cardioverter defibrillator malfunction due to transvenous lead
      insulation break.

PMID- 7513413
TI  - Programming a long paced atrioventricular interval may be risky in DDDR pacing.
AB  - In patients with intermittent AV block and dual chamber pacemakers, a long paced
      AV interval of 200 msec or more can be selected to prolong pulse generator life
      (by avoiding the ventricular pace output) and to enable a more physiological and
      hemodynamically superior activation sequence. This case report describes the
      potential risks of programming a long paced AV interval in a patient with a DDDR
      pacemaker. T wave pacing, as described here, can occur if the conducted QRS
      complex is not sensed because it occurs during the ventricular blanking period
      (delivery of the atrial stimulus). This can be initiated by the mechanisms that
      induce apparent and actual P wave undersensing of the conducted QRS complex. In
      this case report apparent P wave undersensing and subsequent T wave pacing with
      ventricular capture (in a patient with intermittent AV block) occurred frequently
      during an exercise test done in the DDDR mode with a paced AV interval of 200
      msec, according to the clinical evaluation protocol.

PMID- 7513412
TI  - Histopathological study following catheter guided radiofrequency current ablation
      of the slow pathway in a patient with atrioventricular nodal reentrant
      tachycardia.
AB  - The present study examined histological changes induced by catheter guided
      radiofrequency current in a patient with AV nodal reentrant tachycardia who
      underwent cardiac transplantation 1 week after ablation of the slow pathway.
      During the electrophysiology study AV nodal conduction curves were discontinuous
      and AV nodal reentry was induced. At the conclusion of the procedure there was no
      evidence of slow pathway function. Histological sections from the explanted heart
      demonstrated a sharply demarcated atrial lesion (5 x 5 x 4 mm) extending from the
      septal portion of the tricuspid annulus to the posterior border of the AV node.
      The lesion did not encompass the compact AV node. These observations support the
      hypothesis that the slow pathway is comprised of atrial approaches to the AV node
      and is distinct from the compact AV node.

PMID- 7513414
TI  - AVID necessity.

PMID- 7513415
TI  - AVID necessity.

PMID- 7513416
TI  - A serum-free defined medium capable of supporting growth of four established
      human prostatic carcinoma cell lines.
AB  - This paper describes a serum-free defined medium (Gc) that was initially designed
      to support growth of the human prostatic carcinoma cell line LNCaP. Our studies
      indicate that this medium formulation is capable of supporting short-term, long
      term, and clonal growth of the LNCaP cell line. Component deletion experiments
      have shown that the three most critical components for LNCaP short-term growth
      are insulin, triiodothyronine (T3), and fetuin. Additionally, this medium was
      found to support short-term and clonal growth of three other human prostatic
      carcinoma cell lines, DU 145, PC-3, and ALVA-31. The availability of such a
      medium should aid in the distinction of the regulatory factors involved in growth
      and differentiation of malignant prostatic epithelium.

PMID- 7513418
TI  - Thermal changes in the canine prostate after transurethral balloon laser
      prostatectomy.
AB  - The histological changes by transurethral balloon laserthermia were examined on
      23 canine prostates. Immediately after treatment, three zones were observed; the
      coagulative zone treated over 60 degrees C for 20 min formed an inner layer, the
      degenerative zone treated between 60 to 46.1 degrees C surrounded the coagulative
      zone, and the intact zone treated below 46.1 degrees C formed the outer layer.
      Coagulative necrosis of the gland, swelling of collagen fibers, and thrombus of
      the vessels occurred in the coagulative zone, shedding and vacuolation around the
      nuclei of the epithelial cells and stromal edema were observed in the
      degenerative zone, while thermal changes were minimal in the intact zone. Both
      coagulative and degenerative zones developed necrosis and started to slough off
      within 1 week, forming a cavity in the central portion of the prostate.
      Reepithelialization of the cavity was complete at 4 weeks and the ducts of the
      prostate gland opened to the surface of the cavity. This treatment preserved the
      excretory tract of the prostate gland.

PMID- 7513417
TI  - Metastatic prostate cancer pulmonary nodules: beneficial effects of combination
      therapy and subsequent withdrawal of flutamide.
AB  - A case is presented of a middle-aged man suffering from stage D2 prostate cancer
      with pulmonary metastases who responded favorably, first, to endocrine
      combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5
      years, and, second, to the subsequent withdrawal of Flutamide at the time of the
      progression of the disease. This case has several exceptional features: absence
      of bone metastases, pulmonary metastatic nodules characterized as focal
      neuroendocrine differentiation, and a positive response to antiandrogen
      withdrawal upon relapse of metastases after initial positive response. The
      concept of escape to androgen blockade and development of androgenic
      hypersensitivity is discussed.

PMID- 7513419
TI  - Infantile systemic hyalinosis in a black infant.
AB  - A black girl was born with flexion contractures and experienced pain on movement
      by 1 week of age. She subsequently developed perioral papules, gingival
      hyperplasia, perianal nodules, torticollis, diarrhea, rectal prolapse, and
      inability to open her mouth. Her skin became increasingly sclerodermatous, and
      velvety, hyperpigmented plaques arose over bony prominences. A skin biopsy
      specimen showed hyaline material in the papillary dermis with lack of elastic
      fibers. Ultrastructural examination revealed fibrillogranular material around
      fibroblasts and blood vessels. This child had the clinical, histologic, and
      ultrastructural features of infantile systemic hyalinosis. This disorder has not
      been described in a black infant. Previous case reports of infantile systemic
      hyalinosis are reviewed and unusual features of our case are discussed.

PMID- 7513420
TI  - [Tinctorial properties of mycobacteria using standard and nontraditional staining
      technics].
AB  - Tinctural specificity was studied for various mycobacterial species (M.
      tuberculosis Erdman TMC 107, M. tuberculosis Academia, M. Bovis Bovinus-8, M.
      Bovis BCG Russian, M. Avium Avium-53) subjected to staining according to Ziehl
      Neelsen, Boy (fluorescent staining), Gram and Romanovsky-Gimze. The cultures were
      studied on Pavlovsky's continuous medium under natural ageing. The authors tested
      adequacy of diverse bacterioscopic methods for registration of all the cells in
      the mycobacterial population. Mycobacterial morphological and tinctural features
      are shown to be dependent on the culture duration and species. Non-conventional
      Gram's and Romanovsky-Gimze techniques were able to identify L-form granular
      balls and non-acid-fast coccus-like forms. The presence and the number of
      mycobacterial changed forms are species-specific and related to the culture
      duration.

PMID- 7513421
TI  - A study of simulated annealing protocols for use with molecular dynamics in
      protein structure prediction.
AB  - The method of simulated annealing can be of use in protein structure prediction
      by homology modelling where side chain conformations must be predicted. In this
      study an attempt has been made to optimize a molecular dynamics method for this
      purpose. Heating and cooling protocols to maximize the accuracy of the
      predictions have been developed. The optimized protocol involves cooling from
      3000 to 0 K over 20 ps while simultaneously introducing the non-bonded energy
      term. The use of a 'soft' non-bonded interaction energy term in place of a
      standard 6-12 potential is found to be important. The reliability of the
      predictions has been analysed in terms of the environment of the residues
      (solvent accessibility) and the degree of uncertainty in the structure (number of
      unknown torsion angles). Depending on these factors the percentage of unknown
      side chain torsion angles that are correctly predicted within 30 degrees ranges
      from approximately 50 to 75%. Potential problems and limitations of the method
      are discussed.

PMID- 7513422
TI  - Cyclic nucleotide-gated channels: an expanding new family of ion channels.

PMID- 7513423
TI  - Evolutionary origins of ion channels.

PMID- 7513424
TI  - Potentiation of osteoclast bone-resorption activity by inhibition of nitric oxide
      synthase.
AB  - We have examined the effects of modulating nitric oxide (NO) levels on osteoclast
      mediated bone resorption in vitro and the effects of nitric oxide synthase (NOS)
      inhibitors on bone mineral density in vivo. Diaphorase-based histochemical
      staining for NOS activity of bone sections or highly enriched osteoclast cultures
      suggested that osteoclasts exhibit substantial NOS activity that may account for
      basal NO production. Chicken osteoclasts were cultured for 36 hr on bovine bone
      slices in the presence or absence of the NO-generating agent sodium nitroprusside
      or the NOS inhibitors N-nitro-L-arginine methyl ester and aminoguanidine.
      Nitroprusside markedly decreased the number of bone pits and the average pit area
      in comparison with control cultures. On the other hand, NOS inhibition by N-nitro
      L-arginine methyl ester or aminoguanidine dramatically increased the number of
      bone pits and the average resorption area per pit. In a model of osteoporosis,
      aminoguanidine potentiated the loss of bone mineral density in ovariectomized
      rats. Aminoguanidine also caused a loss of bone mineral density in the sham
      operated rats. Inhibition of NOS activity in vitro and in vivo resulted in an
      apparent potentiation of osteoclast activity. These findings suggest that
      endogenous NO production in osteoclast cultures may regulate resorption activity.
      The modulation of NOS and NO levels by cells within the bone microenvironment may
      be a sensitive mechanism for local control of osteoclast bone resorption.

PMID- 7513425
TI  - Redox regulation of signal transduction: tyrosine phosphorylation and calcium
      influx.
AB  - Studies presented here show that altering the intracellular redox balance by
      decreasing glutathione levels profoundly affects early signal transduction events
      in human T cells. In a T-cell receptor (TCR) signaling model, short-term
      pretreatment with buthionine sulfoximine, which specifically decreases
      intracellular glutathione, essentially abrogates the stimulation of calcium
      influx by anti-CD3 antibodies without significantly impairing other aspects of
      TCR-initiated signal transduction, such as overall levels of TCR-stimulated
      tyrosine phosphorylation. In an inflammatory-cytokine signaling model, the
      failure of tumor necrosis factor alpha to stimulate more than minimal tyrosine
      phosphorylation in lymphocytes is overcome by buthionine sulfoximine pretreatment
      -i.e., tumor necrosis factor alpha stimulates extensive tyrosine phosphorylation
      in glutathione-depleted lymphocytes. These redox-dependent changes in T-cell
      responsiveness suggest that the glutathione deficiency that we and others have
      demonstrated in human immunodeficiency virus-infected individuals may contribute
      significantly to the immunodeficiency and the increased inflammatory reactions in
      these individuals.

PMID- 7513427
TI  - Structure of the binding site for nonnucleoside inhibitors of the reverse
      transcriptase of human immunodeficiency virus type 1.
AB  - The dipyridodiazepinone Nevirapine is a potent and highly specific inhibitor of
      the reverse transcriptase (RT) from human immunodeficiency virus type 1 (HIV-1).
      It is a member of an important class of nonnucleoside drugs that appear to share
      part or all of the same binding site on the enzyme but are susceptible to a
      variety of spontaneous drug-resistance mutations. The co-crystal-structure of HIV
      1 RT and Nevirapine has been solved previously at 3.5-A resolution and now is
      partially refined against data extending to 2.9-A spacing. The drug is bound in a
      hydrophobic pocket and in contact with some 38 protein atoms from the p66 palm
      and thumb subdomains. Most, but not all, nonnucleoside drug-resistance mutations
      map to residues in close contact with Nevirapine. The major effects of these
      mutations are to introduce steric clashes with the drug molecule or to remove
      favorable protein-drug contacts. Additionally, four residues (Phe-227, Trp-229,
      Leu-234, and Tyr-319) in contact with Nevirapine have not been selected as sites
      of drug-resistance mutations, implying that there may be limitations on the
      number and types of resistance mutations that yield viable virus. Strategies of
      inhibitor design that target interactions with these conserved residues may yield
      drugs that are less vulnerable to escape mutations.

PMID- 7513428
TI  - The major tyrosine-phosphorylated protein in the postsynaptic density fraction is
      N-methyl-D-aspartate receptor subunit 2B.
AB  - The postsynaptic density (PSD) is a specialization of the submembranous
      cytoskeleton that is visible in the electron microscope on the cytoplasmic face
      of the postsynaptic membrane. A subcellular fraction enriched in structures with
      the morphology of PSDs contains signal-transduction molecules thought to regulate
      receptor localization and function in the central nervous system. We have
      purified a prominent tyrosine-phosphorylated glycoprotein of apparent molecular
      mass 180 kDa, termed PSD-gp180, that is highly enriched in the rat forebrain PSD
      fraction. The sequences of four tryptic peptides generated from the protein
      reveal that it is the 2B subunit of the N-methyl-D-aspartate (NMDA) type
      glutamate receptor. We have confirmed the identity of PSD-gp180 by showing that
      it reacts with antibodies raised against a unique fragment of the 2B subunit of
      the NMDA receptor. We also show that the 2B subunit is the most prominently
      tyrosine-phosphorylated protein in the PSD fraction based upon recognition by an
      anti-phosphotyrosine antibody. Two types of NMDA receptor subunits have been
      identified by molecular cloning [Nakanishi, S. (1992) Science 258, 597-603]. The
      single type 1 subunit is expressed throughout the brain and is necessary for
      formation of the receptor channel. The four type 2 subunits (2A, 2B, 2C, and 2D)
      are expressed in discrete brain regions, contain unusually long unique C termini,
      and confer distinct kinetic properties on NMDA receptors that contain them. Our
      findings suggest that, in the forebrain, NMDA receptor subunit 2B may serve to
      anchor NMDA receptors at the postsynaptic membrane through its interaction with
      the PSD. The prominent presence of tyrosine phosphate further suggests that the
      NMDA receptor may be regulated by tyrosine phosphorylation or that it may
      participate in signaling through tyrosine phosphorylation and through its ion
      channel.

PMID- 7513426
TI  - RNA cleavage and chain elongation by Escherichia coli DNA-dependent RNA
      polymerase in a binary enzyme.RNA complex.
AB  - In the absence of DNA, Escherichia coli RNA polymerase (EC 2.7.7.6) can bind RNA
      to form an equimolar binary complex with the concomitant release of the sigma
      factor. We show now that E. coli RNA polymerase binds at a region near the 3'
      terminus of the RNA and that an RNA in such RNA.RNA polymerase complexes
      undergoes reactions previously thought to be unique to nascent RNA in ternary
      complexes with DNA. These include GreA/GreB-dependent cleavage of the RNA and
      elongation by 3'-terminal addition of NMP from NTP. Both of these reactions are
      inhibited by rifampicin. Hence, by several criteria, the RNA in binary complexes
      is bound to the polymerase in a manner quite similar to that in ternary
      complexes. These findings can be explained by a model for the RNA polymerase
      ternary complex in which the RNA is bound at the 3' terminus through two protein
      binding sites located up to 10 nt apart. In this model, the stability of RNA
      binding to the polymerase in the ternary complex is due primarily to its
      interaction with the protein.

PMID- 7513429
TI  - Analysis of the binding of the Src homology 2 domain of Csk to tyrosine
      phosphorylated proteins in the suppression and mitotic activation of c-Src.
AB  - Csk (C-terminal Src kinase), a protein-tyrosine kinase, bearing the Src homology
      2 and 3 (SH2 and SH3) domains, has been implicated in phosphorylation of c-Src
      Tyr-527, resulting in suppression of c-Src kinase activity. We found that
      mutations in the SH2 or SH3 domain of Csk, though they did not affect its kinase
      activity, resulted in a loss of suppression of c-Src activity in fibroblasts. In
      normal fibroblasts, tyrosine-phosphorylated paxillin and focal adhesion kinase
      pp125FAK, which colocalize at focal adhesion plaques, were the major proteins to
      which the Csk SH2 domain bound. Loss of binding to these proteins by the Csk SH2
      mutants correlated with loss of the activity to suppress c-Src. Consistent with
      this observation, the levels of tyrosine phosphorylation of paxillin and pp125FAK
      were greatly reduced during mitosis, whereas the kinase activity of c-Src was
      elevated. We suggest that the SH2 domain is required for Csk to suppress c-Src,
      perhaps in combination with the SH3 domain, by anchoring Csk to a particular
      subcellular location where c-Src may exist. Our data also indicate that a certain
      fraction of the Csk and Src family kinases function at the focal adhesion
      plaques. The activity of the c-Src kinase localized at the focal adhesion plaques
      appears to be regulated by cell adhesion to the extracellular matrix.

PMID- 7513430
TI  - Heterogeneous activation thresholds to cytokines in genetically distinct
      endothelial cells: evidence for diverse transcriptional responses.
AB  - It is well accepted that the induction of endothelial cell (EC) adhesion
      molecules is a critical component in acute inflammatory responses as well as
      allogeneic interactions in vascularized allografts and, possibly, atherogenesis.
      The "inflammatory triad" of interleukin 1 (IL-1), tumor necrosis factor, and
      lipopolysaccharide are potent stimulators of the EC activation/adhesion molecules
      intercellular adhesion molecule 1 (ICAM-1), endothelial-leukocyte adhesion
      molecule 1 (ELAM-1), and vascular cell adhesion molecule 1 (VCAM-1). To address
      whether there exist differing thresholds to cytokine-mediated EC activation, we
      utilized a panel of genetically distinct human umbilical vein EC lines, assessing
      their modulated EC surface expression and transcriptional responses to cytokines,
      with regard to the cell adhesion molecules (CAMs) ELAM-1, ICAM-1, and VCAM-1.
      With submaximal concentrations of cytokine, EC ELAM-1 surface expression varied
      from negligible to marked. This phenotypic response was maintained over numerous
      passages in culture and was observed in ex vivo organ culture analyses with
      cytokine-treated umbilical vein sections. Relative patterns of ELAM-1, ICAM-1,
      and VCAM-1 induction were similar in response to multiple stimuli (IL-1, tumor
      necrosis factor, and lipopolysaccharide, but not phorbol 12-myristate 13
      acetate). Nuclear run-off experiments demonstrated that the "high responder"
      phenotype is a consequence of enhanced transcriptional activation of the CAM
      genes in response to IL-1 (1 unit/ml), whereas transcriptional responses in "low
      responders" are minimal. Despite the known involvement of NF-kappa B in
      endothelial CAM transcription, gel shift assays failed to demonstrate a
      correlation between the levels of IL-1-mediated nuclear NF-kappa B expression and
      CAM induction in high and low responding lines. We postulate that varying EC
      activation thresholds to cytokines observed here, in vitro, may be a critical
      determinant in the susceptibility to vasculopathic states.

PMID- 7513431
TI  - Lyn tyrosine kinase signals cell cycle arrest but not apoptosis in B-lineage
      lymphoma cells.
AB  - Signal transduction initiated by binding of antibodies to cell surface molecules
      can have an important impact on the growth of tumor cells. The malignant behavior
      of the murine lymphoma BCL1 can be suppressed and the neoplastic cells can be
      induced to enter a dormant state by in vivo ligation of membrane immunoglobulin.
      Anti-CD19 antibodies can prolong the survival of SCID mice challenged with the
      human Burkitt lymphoma cell line, Daudi. Here, we show that cross-linking of
      membrane immunoglobulin on both murine BCL1 and human Daudi cells initiates a
      cascade of signals leading to the induction of both apoptosis and cell cycle
      arrest in vitro. Using antisense oligonucleotides, we demonstrate that the
      immunoglobulin-associated Lyn tyrosine kinase is required for anti-immunoglobulin
      mediated cell cycle arrest but is not required for the signal leading to
      apoptosis. These results define a branch point in the cytosolic signaling
      pathways mediating cell cycle arrest and apoptosis. In Daudi cells, Lyn is also
      critical for cell cycle arrest induced by anti-CD19 signaling. Thus, the Lyn
      tyrosine kinase may be an important mediator of cell cycle arrest in neoplastic B
      lymphocytes and, perhaps, other cell types.

PMID- 7513432
TI  - Thalidomide is an inhibitor of angiogenesis.
AB  - Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in
      humans. We have demonstrated that orally administered thalidomide is an inhibitor
      of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea
      micropocket assay. Experiments including the analysis of thalidomide analogs
      revealed that the antiangiogenic activity correlated with the teratogenicity but
      not with the sedative or the mild immunosuppressive properties of thalidomide.
      Electron microscopic examination of the corneal neovascularization of thalidomide
      treated rabbits revealed specific ultrastructural changes similar to those seen
      in the deformed limb bud vasculature of thalidomide-treated embryos. These
      experiments shed light on the mechanism of thalidomide's teratogenicity and hold
      promise for the potential use of thalidomide as an orally administered drug for
      the treatment of many diverse diseases dependent on angiogenesis.

PMID- 7513433
TI  - Rapid induction of messenger RNA for nitric oxide synthase II in rat neutrophils
      in vivo by endotoxin and its suppression by prednisolone.
AB  - Nitric oxide is believed to participate in nonspecific cellular immunity. Gram
      negative bacterial endotoxins increase the production of reactive nitrogen
      intermediates (RNI) in phagocytic cells by inducing the enzyme nitric oxide
      synthase II (NOS II). Anti-inflammatory glucocorticoids attenuate endotoxin
      induced increases in RNI. This study evaluated the effect of in vivo
      administration of prednisolone on Escherichia coli lipopolysaccharide endotoxin
      (LPS)-induced increases in plasma RNI and neutrophil mRNA for NOS II and
      production of RNI in the rat. We show that LPS rapidly induces mRNA for NOS II
      and production of RNI (NO2- and NO3- anion) in rat neutrophils within 2 hr after
      in vivo administration of a sublethal dose of 0.5 mg/kg, i.v. A pharmacologic
      dose of prednisolone (50 micrograms/kg, im) given 15 min before LPS-attenuated
      production of NO2- and NO3- by neutrophils and suppressed LPS-stimulated mRNA for
      NOS II. 3-Amino, 1,2,4-triazine inhibited NO2- and NO3- production without
      affecting gene expression for NOS II. These data demonstrate that LPS rapidly
      induces functional gene expression for NOS II and prednisolone prevents induction
      of NOS II activity by inhibiting transcription of its mRNA.

PMID- 7513435
TI  - Evaluation of left ventricular functional status using thermodynamic indices.
AB  - Conventional methods to assess cardiac contractility have been focused on the
      mechanical properties of the myocardium. Many of these have suffered from
      theoretical and practical drawbacks. In this study, we have attempted to evaluate
      the left ventricular contractile status using the thermodynamic principle and
      compared these indices with the conventional index (dP/dt). A total of 8 mongrel
      dogs were anesthetized and artificially ventilated. A Millar catheter with high
      fidelity multiple sensors was inserted into the aorta to record the simultaneous
      changes in aortic flow and pressure waves. Cardiac inotropy was increased by
      graded doses (2-32 micrograms/kg/min) of dobutamine. Angiotensin injection (100
      300 micrograms) to achieve a blood pressure elevation of 30 mmHg was employed for
      afterload augmentation. Preload was increased by rapid infusion of 6% dextran
      solution (20 ml/kg). Several thermodynamic parameters were calculated at steady
      state during the control period and after drug interventions. These included
      power-averaged rate of power density generation (ARPD), peak ejection rate of
      change of power (PREP), energy-averaged power density (APD) and frequency
      normalized ARPD (FARPD). PREP and APD were unchanged by afterload increment while
      FARPD, ARPD and dP/dt decreased significantly with an increase in afterload, ARPD
      was highly sensitive to an increased preload (p < 0.001), and PREP was also
      changed significantly by an increase in preload. dP/dt was boarderlinely affected
      by Dextran infusion (p = 0.05), and APD was independent of preload (P > 0.05).
      Inotropic stimulation increased ARPD, PREP, APD, FARPD and dP/dt by 139.0 +/-
      48.0%, 98.0 +/- 51.4%, 74.0 +/- 49.7%, 60.0 +/- 30.4% and 44.6 +/- 10.4%,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513434
TI  - Using the laser pointer as a teaching tool: another suggestion.

PMID- 7513436
TI  - [Excretion of certain micro-molecular proteins in urine of patients with acute
      and chronic virus B hepatitis].
AB  - The aim of the study, was to evaluate the excretion of amylase, lysozyme and beta
      2 microglobulin (B2-M) in patients with acute and chronic virus B hepatitis. The
      gathered findings show the maintained ability of tubules cells to reabsorption
      lysozyme and B2-M. The elevated excretion of amylase in the urine of patients
      with acute viral hepatitis show the transient decrease of abilities to absorb
      this enzyme by teh cells of the tubules. It may be caused by the saturation of
      the catabolic mechanism of the proteins in tubule cells as well as the decrease
      of their energetic abilities due to toxic activity of bilirubin and bile acids.

PMID- 7513437
TI  - [New prospective therapy for benign prostatic hyperplasia with finasteride].
AB  - A randomized, double blind, placebo-controlled study (placebo and Finasteride 1
      or 5 mg/die) was carried out in 34 patients with benign prostatic hyperplasia
      (BPH). After 12 months of treatment all patients received Finasteride 5 mg/die.
      Follow-up ranges from 18 to 36 months. One year after treatment, patients
      receiving Finasteride 1 or 5 mg/die, showed significant decrease (one-way ANOVA)
      of serum dihydrotestosterone (-70.1% and -69.6%, respectively), serum prostate
      specific antigen (-50% and -50.8%, respectively) and prostate volume (-36.3% and 
      31.8%, respectively). Comparable modifications of such parameters were observed
      in the placebo group only during the second year of the study when they were
      shifted to Finasteride treatment (5 mg/die). No increase of serum testosterone
      was observed in any group. Maximum urinary flow rate increased on the average,
      after one year, by 2.6 and 3.6 ml/s in patients receiving Finasteride 1 and 5
      mg/die, respectively; a 1.3 ml/s increase occurred in the placebo group. The
      total urinary symptom score (Boyarsky) decreased in all three patient groups.
      Results of this study show that a few months are necessary to exert a significant
      therapeutic effect. The drug is well tolerated and does not decrease the
      patient's sexual activity. Finasteride certainly opens new perspectives in the
      treatment of BPH.

PMID- 7513439
TI  - Whipple's disease.

PMID- 7513440
TI  - Quality of Life in palliative management of malignant obstructive jaundice.
AB  - Studies comparing different methods of palliating patients with malignant
      obstructive jaundice have mainly concentrated on short-term success and
      complication rates. Seen from the patients perspective, Quality of Life issues
      may be of equal importance. Instruments are being developed and modified to
      permit sequential assessment of Quality of Life as an essential part of any
      studies attempting to evaluate the contribution of different palliative
      procedures.

PMID- 7513438
TI  - Localization of a pernicious anaemia autoantibody epitope on the alpha-subunit of
      human H,K-adenosine triphosphatase.
AB  - Four cDNA fragments encoding different portions of the alpha-subunit of human H,K
      adenosine triphosphatase (ATPase) were amplified by means of the polymerase chain
      reaction technique, ligated into the plasmid pGEX-2T, and expressed as
      glutathione S-transferase fusion proteins in Escherichia coli. The fragments A
      (residues 163-313), Ba (residues 360-797), Bb (residues 526-797), and C (residues
      822-1031) together encompass 77% of the alpha-subunit and cover most of its
      cytosolic part. The reactivities of autoantibodies in the sera from patients with
      pernicious anaemia with the recombinant fusion proteins were analysed by
      immunoblotting. One autoantigenic epitope was found in the NH2-terminal part of
      the Ba fragment--that is, between residues 360 and 525. No epitope was detected
      in the other fragments. The Ba fragment was cleaved off from the glutathione S
      transferase fusion protein by the action of thrombin and was then further
      purified. By means of enzyme-linked immunosorbent assay, 28 of 42 sera (67%) from
      patients with pernicious anaemia were positive against the purified Ba fragment.
      The present results provide a final proof that the human H,K-ATPase alpha-subunit
      is a major autoantigen in the parietal cell and that the major epitope is located
      between residues 360 to 525 on the cytosolic side of the secretory membrane.

PMID- 7513441
TI  - Identification of a peptide recognized by five melanoma-specific human cytotoxic
      T cell lines.
AB  - Of several thousand peptides presented by the major histocompatibility molecule
      HLA-A2.1, at least nine are recognized by melanoma-specific cytotoxic T
      lymphocytes (CTLs). Tandem mass spectrometry was used to identify and to sequence
      one of these peptide epitopes. Melanoma-specific CTLs had an exceptionally high
      affinity for this nine-residue peptide, which reconstituted an epitope for CTL
      lines from each of five different melanoma patients tested. Recognition by
      multiple CTL lines suggests that this may be a promising candidate for use in
      peptide-based melanoma vaccines.

PMID- 7513442
TI  - Outcomes research.

PMID- 7513443
TI  - Control of cell behavior during vertebrate development by Slug, a zinc finger
      gene.
AB  - Slug, a vertebrate gene encoding a zinc finger protein of the Snail family, is
      expressed in the neural crest and in mesodermal cells emigrating from the
      primitive streak. Early chick embryos were incubated with antisense
      oligonucleotides to chick Slug. These oligonucleotides specifically inhibit the
      normal change in cell behavior that occurs at the two sites in the emerging body
      plan in which the gene is expressed. This change, which is the transition from
      epithelial to mesenchymal character, occurs at the formation of mesoderm during
      gastrulation and on emigration of the neutral crest from the neural tube.

PMID- 7513444
TI  - Kyphoscoliosis in Williams syndrome.
AB  - A 10-year-old girl with Williams syndrome (with characteristic facies and
      behavior, mental retardation, and growth disturbances) was seen with scoliosis,
      which, despite attempted bracing, rapidly progressed to 95 degrees and required
      surgical stabilization. Review of the entire literature on Williams syndrome
      revealed hallux valgus and little-finger clinodactyly as the most commonly
      mentioned orthopaedic manifestations, with only brief mention of spinal
      deformity. As awareness of Williams syndrome increases, spine surgeons must be
      aware of possible rapidly progressive scoliosis and kyphosis.

PMID- 7513445
TI  - [Stimulation of myelopoiesis by G-CSF (Filgastrim) in a case oc severe aplastic
      anemia].

PMID- 7513446
TI  - Effects of laminin monoclonal antibodies on the development of cultured rat
      embryos.
AB  - Whole rat embryos (9.5 days of gestation) were exposed to six different
      monoclonal antibodies to laminin during 48 hr of culture. Four (LAM I, LAM V,
      5A2, 9D2) of the six were teratogenic or lethal and two (LAM II, 5D3) were not
      toxic at comparable levels. Teratogenicity and lethality were not related to
      antibody level, subclass or affinity for whole laminin. Indirect
      immunofluorescence studies using mouse embryo sections revealed that the toxic
      antibodies bound in a diffuse manner, while the nontoxic antibodies showed
      distinct labeling of tissues. These observations suggest that previous varied
      responses seen in cultured rat embryos exposed to laminin antibodies obtained
      from humans, monkeys, and rats were the result of differences in the epitope
      specificity of those antibodies.

PMID- 7513447
TI  - Cytoplasmic desmosomes and intermediate filament disturbance following acrylamide
      treatment in cultured rat keratinocytes.
AB  - The present paper describes disturbances in the organization of tonofilaments and
      desmosomes of rat lingual and epidermal keratinocytes after treatment of the
      cells with acrylamide in culture. This treatment induced changes in cell shape,
      reduction of intercellular adhesion and a perinuclear accumulation of cytoplasmic
      organelles. Using specific antibodies for cytokeratins, the filaments were
      disorganized particularly in the perinuclear region. In untreated cells, keratin
      filament labelling was very weak or absent above and below the nucleus thus
      leaving a black nuclear space in fluorescine microscopy. Following acrylamide
      treatment, the keratin filament labelling covered the nuclear space which
      indicated the accumulation of these filaments all around the nucleus.
      Furthermore, the desmosomal junctions were often associated with thick keratin
      bundles. Antibodies for desmoplakins revealed a reduction in intercellular
      labelling and stronger cytoplasmic labelling. Ultrastructurally, well-developed
      long tonofilaments were found to associate with large desmosomal junctions.
      Furthermore, small-sized desmosomal structures were identified within the
      cytoplasm. Morphologically, these were identical to cell surface desmosomes and
      were almost always associated with well-developed tonofilaments. The effect of
      acrylamide on the protein kinase A activity might be implicated in the
      disturbances of the desmosome-intermediate filament complex and in the initiation
      of contractile forces necessary for perinuclear accumulation of intermediate
      filaments and for the formation of intact cytoplasmic desmosomes. The acrylamide
      induced intermediate filament and desmosomal changes may provide valuable
      information on the mechanism of intact cytoplasmic desmosome formation in several
      skin diseases and in squamous cell carcinoma.

PMID- 7513448
TI  - Dicoumarol-sensitive NADPH: phenanthrenequinone oxidoreductase in channel catfish
      (Ictalurus punctatus).
AB  - Phenanthrenequinone (PQ), which occurs widely as a pollutant and as a major
      metabolite of phenanthrene in a number of species, has been demonstrated to
      undergo futile redox cycling leading to oxidative stress. In the presence of
      cytosolic fractions of selected channel catfish tissues, PQ undergoes enzymatic
      reduction which is mediated by either NADH or NADPH and is composed of dicoumarol
      sensitive and -insensitive components. Most notably, gastric cytosol catalyzed a
      disproportionately high level of NADPH-dependent, dicoumarol-sensitive PQ
      reduction as compared to gill, liver, and kidney cytosols. In the presence of
      stomach cytosol and NADPH, PQ facilitated production of superoxide anion at rates
      several fold higher than those mediated by menadione. The dicoumarol-sensitive PQ
      reducing agent, which we have termed NADPH: phenanthrenequinone oxidoreductase
      (PQR), was purified by affinity chromatography and was demonstrated to be
      separable from DT diaphorase activity in gastric cytosol. Under aerobic
      conditions, purified PQR facilitates redox cycling of PQ as indicated by
      continued NADPH oxidation and hydrogen peroxide production. Under anaerobic
      conditions, NADPH oxidation is limited to a quantity indicative of PQ reduction
      to the hydroquinone. Substrate specificities, pH profiles, and kinetic
      characteristics combine to indicate that PQR represents a novel quinone reductase
      in this species.

PMID- 7513449
TI  - Nasal toxicity of chloroform in male F-344 rats and female B6C3F1 mice following
      a 1-week inhalation exposure.
AB  - Chloroform is an important environmental water and air pollutant. Inhalation
      exposure of female B6C3F1 mice and F-344 rats for 6 hr/day for 7 consecutive days
      to 0, 1, 3, 10, 30, 100, or 300 ppm of chloroform resulted in concentration
      dependent lesions in the nasal passages. Chloroform-induced changes included
      increased epithelial mucosubstances in the respiratory epithelium of the
      nasopharyngeal meatus, primarily in the rats. A complex set of responses was seen
      in specific regions of the ethmoid turbinates, predominantly in the rats. These
      lesions in the ethmoid region, which involved all of the endo- and
      ectoturbinates, were most severe peripherally and generally spared the tissue
      adjacent to the medial airways. These changes were characterized by atrophy of
      Bowman's glands, increased numbers of vimentin-positive cells in the periosteum,
      new bone formation, and increased numbers of periosteal cells in S phase as
      determined by bromodeoxyuridine incorporation. Additional changes were site
      specific loss of mucosubstances and loss of immunocytochemical staining of acini
      and ducts of Bowman's glands for P450-2E1 and pancytokeratin, and loss of P450
      2E1 immunostaining of the olfactory epithelium. The only change noted in the mice
      was increased cell proliferation without the osseous hyperplasia. The no-observed
      effect level for these responses ranged from 3 to 100 ppm, with histological
      changes and induced cell proliferation being the most sensitive parameters. It is
      proposed that the osseous changes induced by chloroform exposure may be secondary
      to primary degeneration of adjacent Bowman's glands. The relevance of these
      changes to human health risks include potential damage to the sense of smell, but
      such effects would not be expected at the low levels of chloroform commonly
      encountered in the environment.

PMID- 7513450
TI  - Induction of hepatic acute-phase protein transcripts: differential effects of
      acute and subchronic dimethylnitrosamine exposure in vivo.
AB  - Inflammatory responses are accompanied by increased expression of hepatocyte
      derived proteins collectively known as acute phase reactants (APR). B6C3F1 female
      mice were exposed intraperitoneally every 24 hr to either vehicle (PBS) or DMN (5
      mg/kg) for up to six exposures. Following a single treatment (acute), liver
      tissues were collected at 3, 6, 12, and 24 hr post-exposure. The same collection
      scheme was repeated following the fourth and sixth exposures (subchronic). Total
      cellular RNA was isolated and Northern blot analyses were performed using 3'-end
      radiolabeled oligonucleotides specific for serum amyloid A (SAA), serum amyloid P
      (SAP), and albumin (ALB). SAA transcripts were detected 3 hr after acute DMN
      exposure, peaked at 6 hr, and rapidly declined to vehicle control levels by 12
      hr. No SAA transcripts were observed in vehicle-treated controls. In contrast,
      SAP transcripts were constitutively expressed in both vehicle and DMN-treated
      groups throughout the acute exposure period. However, at 3 and 6 hr after DMN
      exposure, elevated levels of SAP transcripts were observed before returning to
      control levels at 12 and 24 hr. Expression of albumin transcripts decreased
      rapidly following acute DMN exposure and remained suppressed throughout the first
      24-hr period measured. Serum levels of complement component-3 (C3) increased 2 hr
      after a single DMN exposure, whereas decreases in serum albumin levels were first
      observed at 24 hr post-exposure. After four exposures to DMN, SAA transcripts
      were detected at all time periods measured. Similarly, SAP transcripts in livers
      of DMN-exposed animals were consistently elevated above vehicle controls. Results
      after six exposures to DMN were similar, with SAA and SAP transcripts elevated at
      all time points tested. By comparison, repeated vehicle exposures resulted in a
      stress-related transient expression of SAA and SAP transcripts. Thus, acute and
      subchronic DMN exposure resulted in differential APR transcript expression and
      may serve as useful biomarkers following chemical exposure.

PMID- 7513452
TI  - Posttransplant hyperamylasemia is associated with decreased patient and graft
      survival in pancreas allograft recipients.

PMID- 7513451
TI  - Regulation of cytochrome P450 2B1/2 mRNAs by Kepone (chlordecone) and potent
      estrogens in primary cultures of adult rat hepatocytes on Matrigel.
AB  - We previously reported that when primary cultures of rat hepatocytes were treated
      with phenobarbital (PB) or one of several organochlorine pesticides, including
      Mirex, there was co-induction of cytochrome P450 2B1 and 2B2 mRNAs and
      immunoreactive proteins, whereas Kepone selectively induced 2B2 (Kocarek et al.
      (1991) Mol. Pharmacol. 40, 203-210). Indeed, Kepone treatment actively suppressed
      induction of 2B1 and 2B2 mRNAs in hepatocytes cotreated with phenobarbital.
      Because Kepone differs chemically from Mirex only in the replacement of 2
      chlorine atoms with a ketone group, which exists in aqueous solution as a gem
      diol and appears to confer weak estrogenic properties, we treated hepatocyte
      cultures with one of 3 potent estrogens, beta-estradiol, 17 alpha
      ethinylestradiol or diethylstilbestrol. Treatment with each of these estrogens
      induced 2B1 and 2B2 mRNA only at very high doses (10(-4) M). Beta-Estradiol (10(
      4) M) treatment also induced 2B1/2 mRNA in hepatocyte cultures prepared from a
      prepubescent female rat. The anti-estrogen tamoxifen failed to reverse 2B1/2 mRNA
      induction following beta-estradiol or Kepone treatment of adult hepatocyte
      cultures. High doses of beta-estradiol or 17 alpha-ethinylestradiol failed to
      induce 2B1/2 mRNA in treated rats. We also examined the effects of chloral
      hydrate, a simple gem-diol, on 2B1/2 mRNA induction in the hepatocyte cultures.
      Treatment with chloral hydrate (3 x 10(-3) M), like Kepone (10(-5) M), suppressed
      2B1/2 mRNA induction following phenobarbital (10(-4) M) treatment, while Kepone
      alcohol (10(-5) M), which is not a gem-diol, produced less suppression. Our
      results suggest that selective induction by Kepone of 2B2 is unlikely related to
      its effects as a weak classical estrogen, while the ability of Kepone to suppress
      induction of 2B1 and 2B2 by PB may be related to its properties as a gem-diol.

PMID- 7513453
TI  - Combined kidney and pancreas transplantation from pediatric donors into adult
      diabetic recipients.

PMID- 7513455
TI  - Efficacy of human anodal trypsinogen for detection of rejection in clinical
      pancreas transplantation.

PMID- 7513454
TI  - Whole gland pancreas transplantation with portal venous outflow and urinary
      exocrine diversion in mongrel dogs.

PMID- 7513456
TI  - Glucose disappearance constant (KG) provides an alternative diagnostic marker of
      acute pancreas allograft rejection.

PMID- 7513457
TI  - Influence of donor data and organ procurement on human islet isolation.

PMID- 7513458
TI  - Rapid decrease of medium amylase during culture of human and porcine islets.

PMID- 7513459
TI  - Morphometry of native and isolated canine islets: a new approach to isolation
      assessment.

PMID- 7513461
TI  - Gelatin density gradient isolation of hamster islet cells.

PMID- 7513460
TI  - One-hour of hypothermic incubation in Euro-Collins improves islet purification.

PMID- 7513462
TI  - Peritoneal-omental pouch as a site for islet allotransplantation.

PMID- 7513464
TI  - Restitution of intra-islet portal system in pancreatic islet isografts.

PMID- 7513463
TI  - New model for the study of the microcirculation of islet grafts in hairless and
      nude mice.

PMID- 7513465
TI  - Effect of hyperglycemia and of one-week culture of islets on the
      revascularization of pancreatic islet isografts.

PMID- 7513466
TI  - Role of nitric oxide in the pathogenesis of early pancreatic islet dysfunction
      during rat and human intraportal islet transplantation.

PMID- 7513467
TI  - Acceptance of donor-specific islet allografts in rat by intraportal
      preimmunization with islets and FK 506.

PMID- 7513468
TI  - Expression of the regenerating gene in the pancreas of aging mice.

PMID- 7513469
TI  - Functional and morphologic characterization of renal subcapsular islet isografts
      in rats treated with FK 506.

PMID- 7513471
TI  - Prolongation of pig islet xenograft survival in rats by local immunosuppression
      with FK 506.

PMID- 7513470
TI  - Immunohistochemical studies of pig islet xenograft in rats immunosuppressed with
      FK 506.

PMID- 7513473
TI  - Hamster-to-rat xenotransplantation of whole pancreas by FK 506 combined with
      splenectomy.

PMID- 7513472
TI  - Nonvascularized islet xenograft rejection in a mouse-to-rat combination where the
      vascularized heart is rapidly rejected.

PMID- 7513474
TI  - Possible relationship between fibrotic overgrowth of alginate-polylysine-alginate
      microencapsulated pancreatic islets and the microcapsule integrity.

PMID- 7513475
TI  - In vitro and in vivo assessment of viability of dog islets subjected to cold
      storage preservation for 24 hours.

PMID- 7513476
TI  - Suppression of allograft responses by combining alloantigen-specific i.v.
      presensitization with suboptimal doses of FK 506 or rapamycin.

PMID- 7513477
TI  - Cardiotoxicity of long-term intravenous administration of FK506 in rabbits: dose
      relationship and recovery after discontinuance.

PMID- 7513478
TI  - Effect of anti-VCAM-1 and anti-VLA-4 monoclonal antibodies on cardiac allograft
      survival and response to soluble antigens in mice.

PMID- 7513479
TI  - Effects of ET-Kyoto solution on 20-hour canine lung preservation.

PMID- 7513481
TI  - Spontaneous proliferation of peripheral blood mononuclear cells as an indicator
      for insufficient plasma levels of FK 506 in the early phase after liver
      transplantation.

PMID- 7513480
TI  - Primate model of 24-hour pulmonary preservation for clinical application.

PMID- 7513482
TI  - Experimental studies of vascularized joint allografts in rats.

PMID- 7513484
TI  - Treatment of carcinoma oesophagus.

PMID- 7513483
TI  - Analysis of mouse xenogeneic T-cell responses and the effect of FK 506 on these
      responses and on xeno-skin graft rejection.

PMID- 7513485
TI  - [The role of a gastrin-like peptide in regulating the different stages in the
      feeding behavior of snails].
AB  - The role of gastrin-like peptides in a regulation of feeding behaviour was
      studied in a snail Helix lucorum. Sensory stimulation during 15 min carried out
      by a patch of clothes moistened by the carrot juice (pseudo-feeding) decreased
      the weight (by 25-50%) of eaten carrot and the duration of the food intake.
      Similar satiety effect was found after pentagastrin (380 ng) or cholecystokinin
      octapeptide (560 ng) injection 20 min after the beginning of the food intake.
      Measurement of the gastrin-like immunoreactivity showed that the peptide levels
      in the meta-cerebral ganglia and the haemolymph were dependent on the stage of
      feeding behaviour. After pseudo-feeding the peptide levels in the ganglia and the
      haemolymph were significantly higher than those during feeding. Our results
      suggest the presence of a single gastrin/cholecystokinin-like peptide with
      feeding stage-dependent functional significance in Helix snails.

PMID- 7513486
TI  - [A general biological hypothesis on the mechanisms of the effect of different
      psychotropic agents that optimize memory].
AB  - Possibility of interpretation of the effects of psychotropic drugs on memory is
      considered from the viewpoint of general biological conception on molecular
      mechanisms of memory. Previous studies of functional-molecular mechanisms of
      memory in animals at different evolutionary levels, carried out by the author and
      collaborates, became a theoretical basis of the hypothesis proposed. In
      particular, genome modification was established to be induced by learning and
      specific and universal components of memory were revealed. Possibility of genome
      activation in the brain is considered as one of deciding factors in the mechanism
      of memory optimization by psychotropic drugs.

PMID- 7513487
TI  - Upregulation of cell surface expression of T-lymphoid antigens and adhesion
      molecules on acute myeloid leukaemia cells after in vivo administration of
      granulocyte colony-stimulating factor.
AB  - We herein report a case of acute myeloid leukaemia (AML, FAB:M0) who showed
      upregulation of T-lymphoid antigens (CD2, CD7) and adhesion molecules (CD11a,
      CD11b, CD18) on leukaemic cells after in vivo administration of granulocyte
      colony-stimulating factor (G-CSF). To our knowledge, this is the first report
      which describes in vivo changes of cell surface antigen expression on AML cells
      after the administration of G-CSF.

PMID- 7513489
TI  - Immunological investigation for sensorineural hearing loss in the otologic
      clinic: preliminary reports.
AB  - The identification of a possible autoimmune etiology for a sensorineural hearing
      loss (SNHL) is essential for a successful medical treatment. Confirmation of
      diagnosis in clinically "high-risk" patients is provided by antigen-specific
      tests, which are not easily obtainable on a routine basis in the otologic clinic;
      on the other hand the reliability of non-specific-antigen tests is questioned.
      The outcome of serological tests in a group of patients with possible autoimmune
      SNHL were compared with those obtained in two control groups, one of normal
      subjects and one with systemic autoimmune disorders. The test battery included
      the dosage of circulating aspecific autoantibodies (anti-nuclear, anti
      perinuclear factor, anti-mitochondrial, anti-smooth muscle), the total haemolytic
      activity (CH50), the immunoglobulin fractions and the aspecific inflammation
      indexes. At the p level of 0.05, none of the findings reached statistical
      significance, except for low CH50 in 31% of SNHL patients. Complement consumption
      is an indirect indicator of the presence of immunocomplexes. The serum dosage of
      the total haemolytic activity is suggested as screening. Investigation to detect
      circulating immunocomplexes is to be extended to patients with low CH50 levels.

PMID- 7513488
TI  - Analysis of staining methods for different cortical plaques in Alzheimer's
      disease.
AB  - This study evaluated current methods for demonstrating and categorizing cortical
      plaques, with the aim of establishing objective methodology for future diagnostic
      evaluation. Analysis of four methods of tissue processing revealed that the
      highest numbers of plaques were identified in formalin-fixed, paraffin-embedded
      tissue regardless of the stain used. Analysis of three silver stains and four
      immunohistochemical dilutions of an antibody to beta A4 protein revealed that the
      recent silver method published by Garvey et al. [(1990) J Histotechnol 14: 39-42]
      was equivalent to beta A4 immunohistochemistry in demonstrating the highest
      number of plaques. Plaque differentiation was easier and more reliable in silver
      compared to beta A4-stained sections, although the number of identifiable small
      compact plaques was significantly reduced in silver-stained sections. These
      studies show that plaque differentiation may be compromised by tissue processing
      and staining protocols. The establishment of superior methods may provide better
      diagnostic resolution for patients with Alzheimer's disease.

PMID- 7513490
TI  - Scintigraphic detection of early cardiac rejection by iodine 123-labeled
      monoclonal antibody directed against monomorphic determinant of major
      histocompatibility complex class II antigens.
AB  - Although it has been shown that early cardiac rejection can be visualized by
      radioimmunoscintigraphy targeting major histocompatibility complex class II
      antigen, the use of antibodies that bind to a polymorphic determinant of class II
      antigen has certain disadvantages for clinical application. This investigation
      was designed to examine the feasibility of scintigraphic detection of cardiac
      allograft rejection by using a monoclonal antibody that reacts with a monomorphic
      determinant of rat IA antigens. Twenty PVG rats (RT1c) and five DA rats (RT1a)
      underwent heterotopic transplantation with DA hearts. Two of the 20 allografted
      rats were treated with FK506 (2 mg/kg/day). Seventeen rats were injected
      intravenously with 80 microCi of iodine 123-labeled monoclonal antibody reactive
      with a monomorphic determinant of rat major histocompatibility complex class II
      antigens (Ox6) 16 hours before scintigraphy, and images were compared with those
      obtained by injection of 123I-labeled monoclonal antibody against a polymorphic
      determinant of class II antigens (F17-23-6, anti-RT1a) (n = 8). Background
      activity was higher in rats injected with Ox6 than in rats injected with F17-23
      6. Uptake of labeled Ox6 in the grafts reflected the severity of rejection as
      determined by histopathologic criteria. Rejecting allografts with lymphocyte
      infiltration but without myocyte necrosis could be identified by the scintigraphy
      with use of labeled Ox6.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513491
TI  - Interferon treatment of cirrhotic patients with chronic hepatitis C: a logical
      intervention.

PMID- 7513492
TI  - Cholangiography of icteric type hepatoma.
AB  - OBJECTIVES: Icteric type hepatoma caused by floating tumor debris in the major
      bile duct was rare. Such cases were often incorrectly identified as biliary
      carcinoma or choledocholithiasis until pathological proof. The goal of this study
      was to analyze the cholangiograms of icteric type hepatomas, and to identify the
      characteristic cholangiographic features of this rare disease. METHODS: A
      retrospective analysis of 20 cholangiographies of icteric type hepatomas during a
      10-yr period was carried out. RESULTS: There were 15 males and five females in
      this series. Seventeen (85%) patients were hepatitis B virus carriers, and liver
      cirrhosis was detected in 16 (80%) patients. Serum alpha-fetoprotein levels in 13
      (65%) of the patients were over 400 ng/ml. The cholangiographic findings
      included: 1) intraductal filling defects resulting in partial or complete
      obstruction and ductal dilation in 14 cases (70%), 2) abrupt complete obstruction
      of the common hepatic duct with an irregular cut surface in three cases (15%),
      and 3) tumor encasement and stricture of the biliary system in three cases (15%).
      Management of these patients included hepatic resection, choledochotomies with T
      tube stenting, or PTCD. Most of them died within one-half year after diagnosis,
      but one patient in our series, who received hepatic resection, survived more than
      70 months. CONCLUSIONS: It is important to recognize this group of patients.
      Because with proper management, good palliation or cure is possible. The
      cholangiographic appearances, when taken alone, are not diagnostic of icteric
      type hepatomas. Once these cholangiograms are seen in patients with associated
      risks of developing a hepatoma, such as liver cirrhosis, chronic viral hepatitis,
      and elevated serum alpha-fetoprotein, however, an icteric type hepatoma should be
      suspected.

PMID- 7513493
TI  - Fetal hemoglobin synthesis in sickle cell anemia: some molecular considerations.
AB  - An ability to maintain high levels of fetal hemoglobin (Hb F) has been associated
      with the amelioration of the clinical severity of the sickle cell disease (SS).
      Clinical efforts to increase the Hb F level of the patients have, however,
      yielded variable therapeutic response. In an attempt to further elucidate the
      underlying molecular basis, in vitro Hb F synthesis was studied in erythroid
      progenitor (BFU-E) cells obtained from SS patients and their heterozygous (AS)
      relatives with varying genetic backgrounds. This allows us to study the Hb F
      biosynthesis pattern uncomplicated by the influence of the preferential survival
      of "F cells" in vivo. The Hb F levels and the relative concentrations of its
      constituent gamma globin chains, G gamma and A gamma, were assayed using the
      reversed phase HPLC method. A percentage increase in the fetal hemoglobin content
      was observed in the lysates of the erythroid progenitor cells relative to the
      circulating peripheral blood erythrocyte values in SS patients and their AS
      relatives with different beta S haplotypes reflecting the intrinsic capacity of
      fetal hemoglobin synthesis in these subjects. No such increase was observed in
      the patient with the Mor haplotype. Furthermore, the Hb F synthesized in the BFU
      E colonies was more of the adult type, as evidenced by the decrease in the
      percent G gamma level relative to the corresponding peripheral blood values of
      the subjects in all the haplotype groups studied. The Mor haplotype was again an
      exception, synthesizing fetal hemoglobin more of the fetal type.

PMID- 7513494
TI  - G-CSF and GM-CSF in respiratory distress syndrome.

PMID- 7513495
TI  - Effective simultaneous rhG-CSF and methylprednisolone "pulse" therapy in
      agranulocytosis associated with systemic lupus erythematosus.

PMID- 7513497
TI  - Delayed granulocyte response to G-CSF in aplastic anemia.

PMID- 7513498
TI  - Clinical use of growth factors in the myelodysplastic syndromes.

PMID- 7513499
TI  - Pharmacologic therapy for human immunodeficiency virus infection: a review.

PMID- 7513500
TI  - Deciduoid peritoneal mesothelioma. An unusual phenotype affecting young females.
AB  - Two cases of malignant peritoneal mesothelioma are reported. These tumors
      affected young women and displayed an unusual histopathologic pattern that
      closely simulated exuberant, ectopic decidual reaction or at least a malignant
      counterpart thereof. The importance of the differential diagnosis from decidual
      reaction is emphasized because decidua-like mesothelioma appears to be a highly
      malignant neoplasm. The cause of this lesion is unknown; and, considering the
      young age of the patients and the failure to demonstrate hormone receptors in the
      neoplastic cells, it is unlikely that asbestos exposure or hormonal imbalance
      played any role in the development of the disease.

PMID- 7513496
TI  - Increased expression of CD56 and HLA/DR antigens in CD2+ cells from multiple
      myeloma patients.

PMID- 7513501
TI  - Lipofuscin pigmentation (so-called "melanosis") of the prostate.
AB  - Although intraepithelial pigment in the prostate gland has been termed melanosis,
      the nature of the pigment is not entirely clear, and many pathologists are not
      aware of its existence. We examined 863 hematoxylin and eosin (H + E) stained
      slides from 150 surgical specimens of prostate (69 needle biopsies, 66
      transurethral resections, 14 radical prostatectomies, and 1 suprapubic
      prostatectomy) from 149 patients (age range, 47 to 90 years; mean 70 years) in an
      effort to characterize this pigment. The 1-3 microns in diameter, predominantly
      subnuclear, yellow-brown to gray-brown granules with a dark blue rim (by H + E)
      stained positively with Fontana-Masson, periodic acid-Schiff with diastase, Congo
      red, luxol fast blue, and oil-red-O and exhibited yellow autofluorescence
      consistent with lipofuscin. H + E stained slides revealed pigment in the benign
      epithelium in 86 of 150 cases (57%), within stromal macrophages in eight cases,
      and in atypical epithelium in two cases of high-grade prostatic intraepithelial
      neoplasia. Ten cases of invasive adenocarcinoma without recognizable pigment in H
      + E stained sections were stained by the Fontana-Masson technique, and pigment
      was identified in malignant epithelium in three of these cases. Ultrastructural
      examination of intraepithelial pigment in KII-fixed tissue from three radical
      prostatectomy specimens demonstrated the typical appearance of lipofuscin.
      Although intraepithelial pigment in prostatic biopsy or resection specimens is
      usually considered characteristic of seminal vesicle epithelium, our study
      demonstrates that lipofuscin is commonly present in epithelial cells of benign
      prostatic hyperplasia and less frequently in those of prostatic intraepithelial
      neoplasia and adenocarcinoma. The recognition of this pigment is important in
      preventing diagnostic confusion with seminal vesicle epithelium and with
      melanocytic lesions.

PMID- 7513502
TI  - Plexiform malignant peripheral nerve sheath tumor of infancy and childhood.
AB  - We present nine cases of an atypical cellular peripheral nerve sheath tumor,
      designated plexiform malignant peripheral nerve sheath tumor (MPNST) of infancy
      and childhood, occurring in five boys and four girls aged 50 days to 13 years
      (median, 1.5 years). The tumors were located in the lower extremities (five
      cases), upper extremities (three cases), and the orbital region (one case), and
      they ranged from 1.5 to 8 cm in size (median, 3 cm). Two lesions were congenital,
      and another was associated with a history of von Recklinghausen's disease. Follow
      up, available in six cases, ranged from 6 months to 15 years (median, 51 months);
      four patients had local recurrences within 8 to 31 months after excision of the
      initial lesion, and one with an orbital tumor died of locally invasive disease
      within 6 months. Histologically, the initial lesions were characterized by a
      predominantly superficial location within the dermis and subcutis, with
      occasional extension into deeper soft tissues, had infiltrative or sharply
      demarcated margins, and resembled entangled or intertwined hypercellular nerve
      trunks, resulting in a plexiform appearance at low magnification. The nuclei were
      oval to serpentine with a vesicular chromatin pattern and small basophilic
      nucleoli; mitoses were seen in all cases and averaged from 1 to 18/10 high-power
      fields (hpf) (median, 4/10 hpf). Neither necrosis nor vascular invasion was seen.
      Features diagnostic of plexiform or cellular schwannoma, such as nuclear
      pleomorphism, Antoni B areas, thick-walled hyalinized blood vessels, and
      secondary degenerative features were lacking. Other than a prominent plexiform
      architecture, the lesions were indistinguishable from MPNST occurring in other
      sites in infants and children. Although none metastasized, the histologic
      similarity of plexiform MPNST to other childhood MPNST, its relatively high
      propensity for local recurrences, and its potential to behave in a locally
      aggressive manner indicate that it is best regarded as low-grade malignant.
      Overall, the behavior of plexiform MPNST is better than other MPNST in children,
      probably because of its relatively small size, peripheral and superficial
      location in most instances, absence of necrosis or vascular invasion, occurrence
      in young patients, and infrequent association with von Recklinghausen's disease
      rather than a function of its prominent plexiform architecture. Distinction of
      plexiform MPNST from cellular and plexiform schwannoma, plexiform neurofibroma,
      and hamartomatous lesions of childhood is important. Complete excision should be
      ensured to prevent local recurrences and potential metastases.

PMID- 7513503
TI  - Immunohistochemical profile of monoclonal antibody O13: antibody that recognizes
      glycoprotein p30/32MIC2 and is useful in diagnosing Ewing's sarcoma and
      peripheral neuroepithelioma.
AB  - Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are closely related
      tumors, and it can be difficult to distinguish them from other small-round-cell
      tumors (SRCTs). The glycoprotein p30/32MIC2 is highly, but not exclusively,
      expressed in both ES and PN. Although the monoclonal antibody (Mab) HBA71, which
      reacts with P30/32MIC2, has been reported to be relatively specific and highly
      sensitive for both neoplasms, it is not readily available. Yet, Mab O13 is
      commercially available, and it purportedly displays the same immunostaining
      characteristics as HBA71. Because O13 has not been studied extensively, we
      immunostained 21 ES/PNs and 147 other tumors or lesions that might show SRCT-like
      features with O13. The results were similar to those reported for HBA71. We found
      O13 to be 100% sensitive for ES/PN; and, no immunostaining was noted on the SRCTs
      often included in the differential diagnosis of ES/PN (i.e., conventional
      neuroblastoma, rhabdomyosarcoma, and non-lymphoblastic lymphomas). But, O13
      immunoreacted with lymphoblastic lymphomas and some other tumors and normal
      tissues. Nonetheless, this nonspecific reactivity should not cause diagnostic
      problems, if an antibody panel containing anti-desmin and anti-leukocyte common
      antigen is used in conjunction with O13. We conclude that, within the proper
      diagnostic context, strong immunoreactivity of a SRCT tumor for O13 should be
      considered good evidence that the tumor is ES/PN.

PMID- 7513504
TI  - Nodular desmoplastic variant of trichoblastoma.
AB  - A case of an unusual, previously unreported, nodular desmoplastic variant of
      trichoblastoma (hair germ neoplasm) in the scalp of a 65-year-old woman is
      reported. Four discrete nodules were present in close proximity at presentation.
      Another nodule developed in the same vicinity 3 1/2 years after excision, and
      there was no further recurrence 2 1/2 years later. The tumors were located in the
      dermis, made up of cords of primitive hair germ-like structures radiating down
      from discrete hyalinized nodules located in the superficial dermis. There were
      small foci of keratinization or mucoid change within the epithelial islands.
      Toward the deep portion of the tumor, the epithelial cells became spindly and
      grew in a more dispersed pattern, within a desmoplastic stroma. There was also
      infiltration of the epineurium of the cutaneous nerves and arector pili muscle.
      This uncommon benign neoplasm of hair germ merits wider recognition; in
      particular, this desmoplastic variant may mimic invasive carcinoma, morphea-type
      basal cell carcinoma, desmoplastic trichoepithelioma, and desmoplastic
      trichilemmoma. Distinguishing this variant from the former two possibilities is
      particularly important in order to avoid unduly aggressive treatment.

PMID- 7513505
TI  - Expression systems that best mimic native structure: which ones to try first and
      why.

PMID- 7513506
TI  - Interferon therapy for atopic dermatitis reduces basophil histamine release, but
      does not reduce serum IgE or eosinophilic proteins.
AB  - Nine adult patients suffering from severe atopic dermatitis (AD) and increased
      total serum IgE were treated with recombinant human interferon-alpha 2A (Roferon
      AR; IFN-alpha-2A) 3 x 10(6) units daily for 21 d to study the effect upon serum
      IgE, basophil histamine release (HR), eosinophil-derived proteins in serum, and
      clinical symptoms. The skin disease was so severe that all patients needed
      topical treatment with glucocorticosteroid cream. Changes were not observed in
      total serum IgE or in eosinophil-derived proteins, the latter being increased in
      six of nine patients. A significant reduction in basophil HR was found in six of
      nine patients after anti-IgE and concanavalin A (Con A) stimulation, but not
      after A23187 stimulation. The clinical skin score was reduced in eight of nine
      patients at the end of therapy, but disease activity returned to pretreatment
      levels within 3 weeks despite continued topical treatment. rIFN-alpha-2A was well
      tolerated with few clinical side-effects, and all patients completed the study.
      The short-term therapy using IFN-alpha-2A neither brought a sustained clinical
      remission nor reduced total serum IgE or eosinophil-derived proteins. However, a
      significant reduction in IgE-receptor-mediated basophil HR was observed in six of
      nine patients.

PMID- 7513507
TI  - Asthma and contact urticaria caused by rice in a housewife.
AB  - We report the case of an atopic housewife who presented with rhinoconjunctivitis
      asthma and contact urticaria from handling rice and other cereals. She tolerated
      cooke cereals. Both skin prick tests with a rice extract (20% w/v) and a rub test
      with raw rice gave positive results. Bronchial challenge test with methacholine
      revealed a PC20 of 0.45 mg/ml. The challenge test with raw rice resulted in
      immediate and late clinical and spirometric responses; pretreatment with DSCG
      inhibited both responses. The histamine release test (HRT) with rice was
      positive, and we detected rice-specific IgE antibodies by REIA in the patient's
      serum. Skin prick tests, HRT, and RAST with a battery of cereals gave positive
      results. Finally, the rice REIA was inhibited by rice (75%), rye (63%), corn
      (64%), and wheat (51%) extracts.

PMID- 7513508
TI  - Identification of Staphylococcus aureus using a DNA probe: Accuprobe.
AB  - A non-isotopic nucleic probe (Accuprobe) has been presented recently by Gen-Probe
      for the direct specific 1-h identification of Staphylococcus aureus isolated from
      culture. 50 S aureus strains previously characterized by conventional methods as
      well as 26 atypical strains (absence of coagulase, thermonuclease and fibrinogen
      affinity factor) were tested. Moreover, the Accuprobe system was evaluated using
      29 other staphylococcal type strains representing all the species described to
      date. Only the strains that belonged to the S aureus species, including the 26
      atypical strains, were detected by Accuprobe, which proved to be a rapid specific
      mean of identifying S aureus strains, particularly those that are not readily
      identified by conventional methods.

PMID- 7513511
TI  - Serotonin metabolism in the fetus in preeclampsia.
AB  - We investigated serotonin (5-HT) metabolism in the fetus in preeclampsia by
      measuring free 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan
      concentrations in umbilical cord plasma and amniotic fluid, and 5-HT content in
      platelets by high performance liquid chromatography with electrochemical
      detection. Free 5-HT and 5-HIAA levels in umbilical cord plasma were
      significantly higher in the severe preeclamptic group (S) than those in the non
      preeclamptic group (N). The plasma 5-HIAA/5-HT ratio in group S was significantly
      lower than that in group N. Platelet 5-HT content in group S tended to be lower
      than that in group N. Mean plasma beta-thromboglobulin concentration in group S
      was significantly higher than that in group N. There was no significant
      difference in plasma tryptophan levels between group S and N. These findings
      suggest that the higher levels of plasma free 5-HT in umbilical cord plasma in
      preeclampsia are attributable to excess release of 5-HT from platelets as well as
      lower monoamine oxidase activity.

PMID- 7513510
TI  - Hepatitis C virus infection in pregnant women: detection by different anti-HCV
      immunoassays and serum HCV-RNA.
AB  - To assess the seroepidemiology of hepatitis C virus (HCV) infection in pregnant
      women and explore the correlation between different anti-HCV immunoassays, we
      investigated 2 independent groups in Taipei: 1,687 pregnant women without
      screening for serum alanine aminotransferase (ALT) (group A) and 260 pregnant
      women with elevated ALT activity (> 45 IU/l) screened from 15,978 cases (group
      B). In group A, 11 women (0.65%) were found to be anti-HCV-positive by first
      generation tests and 21 (1.24%) by second-generation tests, while 7 (2.69%) and
      15 (5.77%) of the group B subjects were positive, respectively. The results of
      the second-generation assays, based either on recombinant proteins or synthetic
      peptides, were identical. Among the 36 second-generation anti-HCV-positive cases,
      18 (86%) of the 21 cases in group A and 13 (87%) of the 15 cases in group B
      contained serum HCV-RNA by RT-PCR. We conclude that the prevalence of anti-HCV in
      pregnant Taiwanese women is 1.24%, and the prevalence is 5.77% among those with
      an elevated ALT level. HCV-RNA is present in 86% of the cases positive for anti
      HCV. The discrepancy between positive anti-HCV and negative HCV-RNA in some
      pregnant women suggests that anti-HCV positivity in such cases may merely
      represent a past HCV infection or a fluctuating viremia.

PMID- 7513509
TI  - Inhibitory effect of NSAIDs on the chemotaxis induced by substance P on human
      monocytes and polymorphonuclear cells.
AB  - Substance P is involved in the modulation of arthritic pain, and more recently it
      has been suggested that substance P might be involved also in the immunological
      aspects of arthritic diseases. Substance P is present in the synovial fluid of
      arthritic patients, where it can induce the chemotaxis of polymorphonuclear cells
      (PMN) and monocytes, and the synthesis of cytokines. We thought it worthwhile to
      investigate the effect of non steroidal anti-inflammatory drugs (NSAIDs) on the
      chemotactic effect of substance P on PMN and monocytes. We evaluated the effects
      of NSAIDs on the chemotactic effect of two concentrations of substance P that are
      well within those reached by the neuropeptide in arthritic diseases. The
      different NSAIDs inhibit the chemotactic response of PMN with different patterns,
      while the effect on the chemotaxis of monocytes is much weaker. The data we
      present suggest that the effect of NSAIDs on the development and progress of
      arthritic disease could involve their capacity of blocking the chemotactic
      activity of substance P, and with mechanism interfere with the self-feeding
      pathological circle of substance P. It remains to be determined whether the
      effect is mediated by the block of cyclooxygenase or other less specific effects
      of NSAIDs on PMN and monocyte membranes.

PMID- 7513512
TI  - Clinical and pathophysiological evaluation of tranilast in patients with
      pollinosis: the effects of pre-seasonal treatment.
AB  - Tranilast is an orally effective anti-allergic agent evaluated for clinical
      activity in prevention of symptoms of allergic rhinitis. It was investigated in a
      randomized, pre-seasonal, and in-seasonal treatment of tranilast to test the
      clinical efficacy and pathophysiological changes on the onset of nasal symptoms
      in season. Thirty-eight patients with a history of Sugi pollinosis and positive
      allergic tests were treated with tranilast 300 mg daily 6 to 7 weeks before the
      onset of the pollen season and continuously during the season or no medication
      including tranilast until the onset of clinical symptoms in season. The number of
      sneezing and the grade of stuffiness at the onset of pollen season were inhibited
      significantly in pre-seasonal treatment. The number of mast cells and eosinophils
      in season increased compared with off-season and the threshold of nasal
      hypersensitivity in season decreased compared with off-season in inseasonal
      treatment, but not in pre-seasonal treatment. This study indicates that tranilast
      may have the prophylactic effect for Sugi pollinosis.

PMID- 7513513
TI  - Tissue specificity of rat mitochondrial dimethylglycine dehydrogenase expression.
AB  - Expression of mitochondrial dimethylglycine dehydrogenase (Me2GlyDH) was analysed
      in various tissues, liver cell types and developmental stages of the rat. Total
      RNA extracted from liver, spleen, brain, kidney, lung and heart was reverse
      transcribed into cDNA and amplified with Me2GlyDH cDNA-specific oligonucleotides
      by PCR. Expression of the enzyme was observed mainly in liver and kidney. In
      addition, Me2GlyDH mRNA could be demonstrated in total RNA samples of lung, heart
      and brain but was barely detectable in spleen total RNA. In RNA prepared from 14
      day rat embryos, Me2GlyDH-specific mRNA was clearly present. Among various liver
      cell types, besides hepatocytes, endothelial cells showed a high level of
      Me2GlyDH mRNA expression. There was no amplification product detectable in liver
      macrophages (Kupffer cells) and only a very faint one in fat-storing cells (Ito
      cells). Western blots confirmed at the protein level the predominant expression
      of the enzyme in liver and kidney, but Me2GlyDH protein was also present in the
      protein extract of lung, heart, spleen and brain. Immunohistochemical staining of
      liver slices with Me2GlyDH-specific antiserum revealed that expression of this
      enzyme is evenly distributed throughout the liver tissue. In the kidney,
      expression of the enzyme was located in the proximal tubule cells. Our results
      demonstrate that, contrary to the previously assumed liver-restricted expression,
      this enzyme is specifically expressed predominantly in the liver and kidney, but,
      in addition, it is detectable in many other tissues of the rat.

PMID- 7513515
TI  - Expression of myelin-associated glycoprotein isoforms after sciatic nerve crush
      injury in mice.
AB  - The large myelin-associated glycoprotein isoform (L-MAG) protein and small myelin
      associated glycoprotein isoform (S-MAG) protein were demonstrated after sciatic
      nerve crush injury in mice by an immunoblotting technique using specific
      antibodies to the L-MAG protein and the S-MAG protein, respectively. Immunoblots
      indicated a rapid decrease in expression of both isoform proteins in the crushed
      sciatic nerves to < 10% of the control side. By 13 d after injury, L-MAG protein
      expression had quickly recovered to 100% of the control level. Following the
      increase in L-MAG protein expression, S-MAG protein expression recovered to 100%
      by 20 d after injury. It has been reported that the developmental maximum
      expression of L-MAG protein precedes that of S-MAG protein in both central and
      peripheral nervous system (CNS and PNS). Our previous work demonstrated that L
      MAG mRNA was characteristically induced at the time of most active myelination,
      including remyelination in the CNS. We here have shown the expression of L-MAG
      protein precedes that of S-MAG protein during active remyelination in the PNS.
      This suggests that it plays an important role in the early stage of myelin
      formation.

PMID- 7513516
TI  - [Ginkgo extract EGb 761 (tenobin)/HAES versus naftidrofuryl (Dusodril)/HAES. A
      randomized study of therapy of sudden deafness].
AB  - 80 patients with idiopathic sudden hearing loss existing no longer than 10 days
      were included in a randomised reference-controlled study. The therapeutic value
      of Ginkgo EGb 761 (Tebonin) + HAES was compared to that of Naftidrofuryl
      (Dusodril)+HAES. The main mechanisms of action of EGb 761 are a vasoregulating
      activity (increased blood flow), the platelet activating factor antagonism and a
      prevention of membrane damage caused by free radicals. Naftidrofuryl has
      antiserotonergic and therefore vasodilatory properties. The statistical analysis
      of the audiometric data was performed in measuring the relative hearing gain as
      described by Eibach 1979. After one week of observation, 40% of the patients in
      each group showed a complete remission of hearing loss. This was also observed by
      other authors who had compared other drugs. Therefore, in these cases, it is most
      likely that spontaneous recovery is the most important factor. After two and
      three weeks of observation, measuring the relative hearing gain, there was a
      significant borderline benefit of EGb 761 (p = 0.06) without any side effects.
      Some patients of the reference group developed side effects such as orthostatic
      dysregulation or headache or sleep disturbances. Minimising side effects should
      be one of the most important goals in therapy of sudden hearing loss until the
      efficiency of infusion therapy is proved.

PMID- 7513517
TI  - The riddle of the mast cell: kit(CD117)-ligand as the missing link?
AB  - Tissue mast cells are multifunctional immune cells and have been implicated in
      allergic and inflammatory reactions. However, while the role of allergen binding
      to surface IgE via the high-affinity Fc epsilon receptor on mast cells is well
      understood, major questions in mast-cell biology remain to be answered. In
      particular, it is largely unknown which stimuli lead to the differentiation of
      human mast cells from their precursor cells and how the maturing cells localize
      (or home) and acquire effector functions within the microvasculature. A potential
      solution is suggested by Peter Valent in this viewpoint. The emerging concept is
      that a single tissue hormone, the ligand of the c-kit tyrosine kinase receptor
      (CD117), provides a key signal in multiple aspects of mast-cell differentiation
      and function.

PMID- 7513518
TI  - Is malaria linked to the absence of alpha-galactosyl epitopes in Old World
      primates?

PMID- 7513519
TI  - A physiological role for circulating adhesion molecules?

PMID- 7513520
TI  - Beta-subunit of human chorionic gonadotropin hormone and firefly luciferase
      simultaneously synthesized in insect cells using a recombinant baculovirus are
      differentially expressed and transported.
AB  - A recombinant baculovirus vAc beta hCG-luc was constructed that carried the cDNAs
      encoding firefly luciferase (luc) and beta-subunit of human chorionic
      gonadotropin (beta hCG) placed under the transcriptional control of individual
      copies of the baculovirus polyhedrin gene promoter. The simple, rapid, and
      sensitive detection of LUC expression was used for selecting recombinant viruses
      that simultaneously expressed beta hCG, which was identical in all respects to
      that synthesized using a recombinant baculovirus carrying the beta hCG gene
      alone. Immunofluorescence staining of virus-infected cells using anti-LUC
      antibodies revealed that LUC, a nonglycosylated, intracellular protein was
      retained within the cells whereas beta hCG, an extensively glycosylated,
      secretory protein, was processed and secreted into the culture medium. LUC and
      beta hCG were both immunoreactive on Western blot. beta hCG was bioactive, as
      evident from its ability to associate with alpha hCG and bind with the receptor
      and produce testosterone in an in vitro mouse Leydig cell assay system.
      Comparison of recombinant LUC and beta hCG synthesized by the virus-infected
      insect cells surprisingly revealed that the level of the former was
      quantitatively higher by at least 10-fold than the latter. A blot of total RNA
      isolated from vAc beta hCG-luc-infected insect cells, when probed with probes
      corresponding to the 3' region of the beta hCG or luc genes, indicated
      differential transcription of the two genes. Computer-aided sequence analysis
      indicated extensive secondary structure and stem-loop complex-forming potential
      of the beta hCG gene, which could be responsible for the transcriptional
      difference observed.

PMID- 7513514
TI  - Cell proliferation status, cytokine action and protein tyrosine phosphorylation
      modulate leukotriene biosynthesis in a basophil leukaemia and a mastocytoma cell
      line.
AB  - Mast cells, mastocytoma cells and basophil leukaemia cells are well-established
      producers of leukotrienes when grown and stimulated appropriately. I report that
      the cells' ability to produce leukotrienes is dependent on the cells'
      proliferative status or their provision with growth factors. Proliferating MC/9
      and subconfluent RBL2H3 cells respond maximally to stimulation by 1 microM
      ionomycin with the production of 56 and 32 pmol of cysteinyl-leukotrienes/10(6)
      cells respectively. In contrast, confluent RBL2H3 or growth-arrested MC/9 cells
      lose their ability to generate leukotrienes in response to ionomycin treatment.
      This rapid down-regulation of leukotriene synthesis is also observed when
      proliferating RBL2H3 cells are transferred to growth-factor-free medium, wherein
      cellular leukotriene-synthesis capacity has an apparent half-lifetime of 60 min.
      Transfer back into growth medium results in the regeneration of leukotriene
      synthesis capacity within 6 h. In growth-arrested MC/9 cells, leukotriene
      production ability can at least partially be restored by priming the cells with
      interleukin 3, but not with interleukin 4. In RBL2H3 cells, pretreatment with
      protein tyrosine kinase inhibitors such as genistein (5 min, 37 microM),
      herbimycin A (6 h, 3 microM) or tyrphostin 25 (16 h, 100 microM) completely
      inhibits leukotriene generation, whereas okadaic acid (15 min, 0.5 microM) has no
      effect. Under these conditions, both genistein and herbimycin A strongly impair
      ionomycin-induced protein tyrosine phosphorylation. Our study indicates that
      leukotriene generation in these tumour cells is tightly regulated by their
      proliferation status and supply with growth factors, and cell stimulation towards
      leukotriene synthesis appears to involve protein tyrosine kinase activity.

PMID- 7513521
TI  - Recognition of endotoxin by cells leading to transmembrane signaling.
AB  - Bacterial endotoxins act at picomolar to nanomolar concentrations to stimulate a
      wide variety of cell types including phagocytic and endothelial cells. The major
      elements identified to date that are crucial for recognition of endotoxin are
      lipopolysaccharide (LPS)-binding protein, membrane-bound CD14 and, most recently,
      soluble CD14. Recent results also indicate that membrane-bound CD14 is probably
      one part of a multi-component LPS receptor. An immediate consequence of
      engagement of this functional LPS receptor is protein tyrosine phosphorylation
      and initiation of the multiple intracellular events associated with LPS-induced
      cell activation.

PMID- 7513522
TI  - Structure of peptides associated with MHC class I molecules.
AB  - Recent progress in understanding the structures of MHC class I molecules and the
      peptides that they bind has led to a generalized model for peptide binding, and
      an understanding of allelic specificity. Prediction on the basis of motifs and
      new techniques for peptide analysis have recently resulted in the identification
      of several peptides that comprise epitopes for antigen-specific T cells.

PMID- 7513523
TI  - Assembly and regulation of NADPH oxidase and nitric oxide synthase.
AB  - Research over the past year has revealed several interesting advances in the
      biosynthesis of the superoxide anion and nitric oxide. Highlights include the
      demonstration that the G protein Rac 2 is required for NADPH oxidase activation,
      the finding that nitric oxide is a feedback inhibitor of nitric oxide synthase
      isoforms, and the discovery that the continuous catalytic activity of the
      immune/inflammatory nitric oxide synthase is due to strong calmodulin binding,
      which is independent of elevated calcium levels. Interferon-gamma primes
      neutrophils and macrophages for both O2- and nitric oxide synthesis. However,
      NADPH oxidase and immune/inflammatory nitric oxide synthase are differentially
      regulated such that their activities are not simultaneously induced.

PMID- 7513524
TI  - Methods to study peptides associated with MHC class I molecules.
AB  - It is now an accepted fact that peptides of self or non-self origin form an
      essential component of the MHC class I structure. The peptide component of the
      heterotrimer contains the essential determinants recognized by the T-cell
      receptors of cytotoxic T lymphocytes, be it an antigen-specific, alloimmune or
      autoimmune response. Because of the importance of the recognition process,
      several methods have been developed to characterize naturally processed peptides
      presented by the class I molecules.

PMID- 7513525
TI  - Origin, structure and motifs of naturally processed MHC class II ligands.
AB  - In the past few years a considerable number of naturally processed MHC class II
      ligands have been identified and sequenced. Most of them derive from endogenous
      sources, predominantly from plasma membrane proteins. Generally, they display
      variability in length but exhibit characteristic patterns of invariant amino acid
      positions, which reflect the allele-specific binding requirements. As a general
      feature, class II ligands also often contain a pattern of proline residues
      interpreted as a 'processing motif'.

PMID- 7513526
TI  - Defining rules for the peptide-MHC class II interaction.
AB  - Recent work has begun to clarify the molecular events governing peptide
      interaction with MHC class II proteins. The requirements for peptide binding to
      class I and class II molecules seem to be similar. Despite differences in peptide
      length, anchor residues defining allele-specific peptide motifs can also be found
      in class II binding peptides. The presence of conserved and allele-specific
      anchors appears to explain the promiscuity and the specificity of peptide
      recognition by DR molecules.

PMID- 7513527
TI  - Selectins.
AB  - The selectins are three related receptors that initiate rolling of leukocytes on
      activated platelets or endothelium through Ca(2+)-dependent recognition of cell
      surface carbohydrates. Cell adhesion may be enhanced by a limited number of
      membrane glycoproteins that present high affinity carbohydrate ligands to
      specific selectins. The synthesis and surface display of the selectins is
      normally tightly controlled, but inappropriate expression may contribute to
      inflammatory disorders. Recent in vivo studies confirm the importance of the
      selectins in both physiological and pathological leukocyte recruitment.

PMID- 7513528
TI  - Microbial transformation of immunosuppressive compounds. III. Glucosylation of
      immunomycin (FR 900520) and FK 506 by Bacillus subtilis ATCC 55060.
AB  - The regiospecific glucosylation of FK 506 and immunomycin (FR 900520) at the 24
      hydroxy position was performed using resting cells of Bacillus subtilis ATCC
      55060. 24-Glucopyranosyl FK 506 and 24-glucopyranosyl immunomycin were isolated
      by methylene chloride extraction and purification using reverse phase HPLC. The
      metabolite structures were established using spectroscopic techniques including
      MS and NMR. The glucose conjugate was further confirmed by chemical degradation.
      Enzymatic glucosylation was demonstrated using cell-free extracts derived from
      Bacillus subtilis ATCC 55060. The 24-glucosyltransferase, which appears UDP
      glucose dependent, was solubilized from cell membranes by treatment with 0.1%
      Nonidet P-40 detergent. The optimal conditions for assay of the enzyme have been
      determined.

PMID- 7513531
TI  - Hormone therapy prior to radical prostatectomy in patients with clinical stage C
      prostate cancer.
AB  - Seventy patients with clinical stage C carcinoma of the prostate were treated for
      3 months with the gonadotropin-releasing hormone analog, goserelin acetate
      (Zoladex; Zeneca Pharmaceuticals, Macclesfield, UK) plus an antiandrogen
      (flutamide). Based on digital rectal examination (DRE), reductions of the size of
      the prostate and the tumor were noted in 91.4% of patients. Ultrasound
      demonstrated a decrease in prostatic volume between 0% and 62.5% (median 31%).
      Prostate-specific antigen (PSA) levels (Hybritech) decreased substantially (mean
      PSA of 31.3 ng/ml before, to a mean PSA of 1.4 ng/ml after hormonal treatment). A
      total of 64 patients subsequently underwent radical retropubic prostatectomy.
      Pathologically, only 9 patients (14.1%) had organ-confined disease (stage B), 34
      (53.1%) had stage C tumors, and 21 (32.8%) had positive lymph nodes (stage D1).
      In 5 patients with nodal metastasis and 7 patients with seminal vesicle invasion,
      PSA levels after pretreatment were below 0.5 ng/ml. Maximal androgen blockade for
      a period of 3 months in clinical stage C prostate cancer induces a notable
      reduction in prostate size ("downsizing"). A "downstaging" effect, as suggested
      by DRE, ultrasound, and PSA, was not observed. Prospective studies with this
      treatment regimen should concentrate on a possible benefit concerning local and
      distant cancer control and survival.

PMID- 7513532
TI  - Neoadjuvant androgen blockade prior to prostatectomy: a retrospective study and
      critical review.
AB  - The treatment of locally advanced prostatic cancer is controversial, as there are
      several possible treatment options. The aims of temporary androgen deprivation
      prior to radical prostatectomy are to achieve downgrading and downstaging of the
      tumor, an increase in local control, a decrease in morbidity and operative
      sequelae, a decrease in the time to progression, and an improvement in survival.
      A retrospective study has been carried out on 100 patients who underwent radical
      prostatectomy between 1988 and 1992. Forty patients received androgen deprivation
      therapy followed by prostatectomy, while the remaining 60 acted as controls,
      undergoing prostatectomy alone. Treated patients had a 40-50% reduction in
      prostate volume after 3 months, facilitating dissection of the prostate, reducing
      intraoperative blood loss, and reducing operation time. Of these 40 treated
      patients, one third showed clinical downstaging; one patient staged initially as
      T2/B was downstaged to PT0. The proportion of patients with positive surgical
      margins was 32% in the group treated preoperatively, compared with 57% in
      untreated patients. Treated patients also recovered full continence more rapidly
      after the operation than patients who underwent prostatectomy alone. After
      androgen blockade, serum PSA levels returned to normal (< 4 ng/ml) in 37 of the
      40 patients. Of these patients, 22 had undetectable serum PSA levels (< 0.25
      ng/ml), showing a definite reduction in tumor activity. PSA levels after 3 months
      of neoadjuvant hormonal treatment might play a useful predictive role in
      selecting patients before radical prostatectomy, since 86% with undetectable PSA
      had tumors confined to the gland (T2/B2), while patients who still had PSA > 4
      ng/ml all had stage T3-T4 tumors. Although downstaging was confirmed
      pathologically in only 13% of patients, this is of significance when the total
      number of patients with locally advanced prostate cancer is considered and,
      therefore, may have implications for survival in the future. Prospective
      randomized studies should provide conclusive information on the potential benefit
      of this approach.

PMID- 7513530
TI  - Role of prostate-specific antigen as a predictor of outcome in prostate cancer.
AB  - Prostate-specific antigen (PSA) has been shown over the past few years to be a
      useful and sensitive marker for prostate cancer. During Phase III studies of the
      nonsteroidal antiandrogen, Casodex, in which different doses were compared with
      castration (either surgical or medical), serum PSA was measured on a regular
      basis. Attention was focused on the change in serum PSA from baseline after 3
      months Casodex treatment and also on the number of patients receiving Casodex
      whose PSA returned to the normal range. Data from trials comparing Casodex, 50
      mg/day, with castration showed a clear shortfall for Casodex compared with
      castration, in terms of percentage fall in PSA at 3 months, and also in the
      number of patients whose PSA fell into the normal range after 3 months.
      Subsequent analysis showed, however, that the PSA level was related to outcome in
      terms of time to progression. These data allowed the use of PSA to determine dose
      selection in a subsequent trial comparing Casodex, 100 mg/day or 150 mg/day, with
      castration. At the time of dose selection, changes in PSA showed a statistically
      significant difference between Casodex, 100 mg/day, and castration, but no
      significant difference between Casodex, 150 mg/day, and castration, either for
      the change in PSA at 3 months or for the proportion of patients whose PSA had
      fallen into the normal range. The idea that serum PSA levels can predict outcome
      in prostate cancer and that they are correlated with other measures of outcome,
      such as time to progression, is supported by these data. A decrease in PSA is not
      a true surrogate endpoint in that it cannot predict the outcome for an individual
      patient with complete accuracy, but it does correlate well with other measures of
      outcome, such as time to progression, for patient populations.

PMID- 7513533
TI  - Aprotinin and bleeding in profoundly hypothermic perfusion.
AB  - Clinical observation led us to believe that aprotinin fails to preserve
      haemostatic function in patients undergoing deep hypothermic perfusion with or
      without circulatory arrest. A retrospective study was made of blood loss in 80
      consecutive acute Type A dissection patients before and during the aprotinin era
      (1987-1992). After 1988 all patients were cooled below 20 degrees C pending
      circulatory arrest. Fourteen patients underwent aortic root replacement and 66
      replacements of the ascending aorta. Age distribution (range 22-79 years) and
      type of operation were similar in the aprotinin and control groups. The
      impervious Hemashield (Meadox) graft was used for all but five patients. These
      underwent aortic root replacement with preclotted, valved conduits. Overall the
      mean blood loss for 27 patients operated without aprotinin was 837 ml per 24 h
      (standard error +/- 90) and for 53 patients with aprotinin 1,929 ml per 24 h
      (standard error +/- 90). There was a significant difference between the two
      groups when profoundly hypothermic perfusion was used, with greater bleeding in
      aprotinin-treated patients. There were six re-entries in the aprotinin group and
      none in the control patients. There were ten hospital deaths (11.1%). A greater
      incidence of bleeding and thrombosis-related deaths was recorded for the
      aprotinin-treated patients. In addition, four surviving aprotinin patients
      suffered severe coagulation defect with blood loss greater than 4,500 ml and
      platelets less than 50 x 10(6). We suggest that aprotinin inhibits the protease
      enzymes which maintain the fluid state of blood during hypothermic low flow and
      arrest states. Disseminated intravascular coagulation may consume platelets
      thereby predisposing to abnormal bleeding and potentially fatal thrombotic
      events. The use of aprotinin in profoundly hypothermic perfusion should be
      adopted cautiously.

PMID- 7513535
TI  - Acidification of human brains stored in fixatives.

PMID- 7513529
TI  - Effect of glucose on the expression parameters of recombinant protein in
      Escherichia coli during batch growth in complex medium.
AB  - The expression parameters were determined at different phases of batch growth of
      Escherichia coli JM101/pYEJ001 in complex medium and at different conditions of
      glucose addition. Thus the plasmid content, the RNA content, the RNA synthesis
      rate, the specific recombinant mRNA content, the specific recombinant mRNA
      synthesis rate, the recombinant chloramphenicol acetyltransferase content, and
      the overall protein synthesis rate were determined during growth with no glucose,
      with initial glucose, with glucose feeding during stationary phase, and with
      initial glucose plus glucose feeding during stationary phase. The results show
      that the specific rate of total RNA synthesis was enhanced in the presence of
      glucose at both exponential and stationary phases, while recombinant mRNA
      synthesis was enhanced only at stationary phase by glucose feeding. However, the
      steady-state level of the recombinant mRNA was not changed under the same
      conditions. In addition, although the overall protein synthesis rate at
      exponential phase was enhanced in the presence of glucose, the specific
      recombinant protein level was unaffected. The specific synthesis rate of
      recombinant mRNA varied inversely with the plasmid content during exponential and
      stationary phases. Furthermore, changes in the specific activity of the
      recombinant protein were not correlated with either the changes in the specific
      synthesis rate of the recombinant mRNA or the overall protein synthesis rate.
      Therefore, the specific activity of the recombinant protein is not universally
      limited by its gene transcription rate or the overall protein synthesis capacity.

PMID- 7513534
TI  - Aprotinin effect on platelet function and clotting during cardiopulmonary bypass.
AB  - A variety of studies have been performed on the preservation of hemostasis by
      aprotinin during cardiopulmonary bypass (CPB). It appears that the mechanism of
      aprotinin to preserve hemostasis can be interpreted in different ways. Our
      previous studies suggested that preservation of platelet glycoprotein Ib (GpIb)
      antigen, and counteraction of heparin anticoagulation in the extrinsic clotting
      pathway might partly explain the preservative effect of aprotinin. A clinical
      study was therefore conducted to evaluate these effects during the use of low
      dose aprotinin. Improved agglutination by ristocetin (P < 0.05), and improved
      GpIb antigen expression (P < 0.05) during CPB showed better preserved platelet
      adhesive capacity in the aprotinin group than in the control group. Glycoprotein
      Ib antigen expression and the agglutination capacity with ristocetin during CPB
      were closely related (P < 0.05). Platelet GpIIb/IIIa antigen and adenosine
      diphosphate (ADP) aggregation were not significantly different between the
      aprotinin and control groups. Aprotinin had no effect on the extrinsic clotting
      pathway in the blood, since the thromboplastin clotting time was similar in both
      groups. These results indicate that the protection of platelet adhesive capacity
      during CPB is a main function of aprotinin, whereas no evidence was collected for
      enhanced extrinsic clotting by aprotinin during CPB.

PMID- 7513536
TI  - Quality of life assessment in palliative care.
AB  - Palliative care aims to improve the quality of life of patients through attention
      to physical, psychological, social and spiritual distress. Assessment of quality
      of life, expressed as a global score, is difficult because patients are too ill
      for long interviews, but relatives and professionals are poor proxy respondents
      for patients. Quality of life assessment tools must be multidimensional,
      considering both physical and psychosocial issues, must be quick and easy to
      administer and score and must be sufficiently sensitive to detect changes with
      time. Quality of life assessment has audit and routine clinical uses; it is an
      essential consideration in any research involving the patient with advanced
      cancer. The different types of questionnaire assessment tool are discussed in
      detail.

PMID- 7513537
TI  - Disseminated growth of Hodgkin's-derived cell lines L540 and L540cy in immune
      deficient SCID mice.
AB  - Local tumor growth has been reported after subcutaneous and intraperitoneal
      injection of Hodgkin's disease (HD) derived cell lines into different
      immunodeficient mouse strains. An animal model with disseminated growth of tumor
      cells would be useful for studying the in vivo biology of HD cells as well as for
      preclinical testing of new therapeutic regimens. For this purpose the HD-derived
      cell lines L540, L540cy, L428, and KM-H2 were injected intravenously into SCID
      mice. In contrast to L428 and KM-H2, widespread neoplasia occurred after a period
      of four to six weeks following injection of L540 and the subline L540cy. Lymph
      nodes were found to be the preferred site of tumor growth. CD30 surface antigen
      expression on Hodgkin cells and the karyotype of the tumor cells were preserved
      in the animal host. Thus, to a large extent, the SCID mouse model mimics the
      dissemination pattern of Hodgkin's disease in man. To evaluate the role of
      adhesion molecule expression in the dissemination of HD-derived cell lines, CD44
      and members of the immunoglobulin, integrin, selectin, and Fc receptor families
      were quantified by flow cytometry. CD30 expression was also measured. Although
      CD44 expression has been correlated with dissemination in non-Hodgkin's lymphoma
      (NHL), this was not the case in the Hodgkin's SCID mouse model. CD44 was not
      expressed on the disseminating cell lines L540 and L540cy but was expressed in
      the nondisseminating lines L428 and KM-H2.

PMID- 7513538
TI  - A comparison of two radiotherapy regimens for the treatment of symptoms from
      advanced bladder cancer.
AB  - Pain and haematuria are two of the most distressing symptoms in patients with
      advanced bladder cancer. The aim of palliative radiotherapy is to relieve these
      symptoms with the minimum of stress to the patient and with minimal side effects.
      Two treatment regimens were studied: hypofractionated radiotherapy giving 1700
      cGy in two fractions over 3 days and conventional palliative radiotherapy giving
      4500 cGy in 12 fractions over 26 days. This study assesses 41 patients, all with
      Grade II-III T3-4 transitional cell carcinomas of the bladder treated between
      1982 and 1989, presenting with haematuria and local pain. Two-fraction
      (hypofractionated) treatment was given to 22 patients and conventional palliative
      radiotherapy to 19; patients were selected by performance status. The effect on
      haematuria was assessed as cleared, intermittent or persistent. Pain was assessed
      by noting reduction in the need for opiate analgesia. Any side effect was
      recorded. In the patients receiving two-fraction radiotherapy, 59% had clearance
      of the haematuria and in 73% there was improvement of their pain, compared with
      16% and 37% respectively in those receiving conventional palliation. Survival of
      the two groups was 9.77 months and 14.47 months respectively. Side effects were
      trivial in both regimens. Radiotherapy given in two fractions for patients in
      poor general health is well tolerated and less distressing than the standard
      palliative regimen with 12 fractions. Haematuria and pain were more effectively
      palliated than with conventional treatment, though survival was shorter. We
      conclude that hypofractionated radiotherapy may be the palliative treatment of
      choice and the study supports the need for a prospective assessment of this
      treatment approach.

PMID- 7513539
TI  - At least two different regions are involved in allelic imbalance on chromosome
      arm 16q in breast cancer.
AB  - Loss of heterozygosity (LOH) or allelic imbalance, the latter term referring to
      both loss and gain of an allele, on the long arm of chromosome 16 has been
      repeatedly found in cancers of, e.g., the breast and prostate. This indicates the
      presence of one or more tumor suppressor genes on 16q. To locate the gene(s) more
      precisely, a detailed allelic imbalance map of 20 polymorphic markers on this
      chromosome arm was made for 79 sporadic breast carcinomas. LOH of one or more
      markers was found in 63% of the tumors. Some had allelic imbalance on a region of
      16q which failed to overlap with the LOH in other tumors. We therefore assigned
      two separate "smallest regions of overlap" to 16q and suggest that this
      chromosome arm contains at least two different tumor suppressor genes.

PMID- 7513540
TI  - The spectrum of TP53 mutations in bladder carcinoma.
AB  - The mutational spectrum for the TP53 gene was investigated in a large series of
      bladder tumors and bladder tumor cell lines. Tumors and cell lines were screened
      for the presence of TP53 point mutations by single-strand conformational
      polymorphism analysis followed by direct sequencing. Mutations were detected in
      16 of 88 (18%) tumors and 4 of 14 cell lines (28%). In total, twelve missense
      mutations, one nonsense mutation, three deletions, and two insertions were
      identified by direct sequencing. Of the thirteen point mutations sequenced, only
      one was a transition at a CpG site, whereas five G:C-->T:A transversions were
      found, suggesting a major role for exogenous mutagens in bladder tumorigenesis.
      Tumors were also examined for loss of heterozygosity (LOH) on chromosome arm 17p.
      LOH of one or more markers on 17p was detected in 31% of tumors. All eight tumors
      with a TP53 mutation from patients informative at TP53 had LOH, whereas nine
      tumors with LOH at TP53 did not have an identified mutation. Three tumors had LOH
      on 17p at sites distal to the TP53 locus but retained both TP53 alleles,
      suggesting the involvement of another tumor suppressor gene on 17p in bladder
      tumorigenesis in some tumors.

PMID- 7513541
TI  - Allelotype of uterine cancer by analysis of RFLP and microsatellite
      polymorphisms: frequent loss of heterozygosity on chromosome arms 3p, 9q, 10q,
      and 17p.
AB  - Cancers in which mutations have been identified in putative tumor suppressor
      genes, such as the TP53 gene, the retinoblastoma (RBI) gene, the adenomatous
      polyposis coli (APC) gene, and the Wilms tumor (WTI) gene, frequently show loss
      of the corresponding allele on the homologous chromosome. To identify locations
      of tumor suppressor genes involved in uterine cancer, we examined loss of
      heterozygosity (LOH) by using genomic probes detecting RFLPs in 35 uterine
      cancers at 29 loci throughout the genome, and with highly informative
      microsatellite markers in 21 uterine cancers at nine putative or known tumor
      suppressor gene loci. High frequencies of allelic loss found at loci on 3p (71%),
      9q (38%), 10q (35%), and 17p (35%) suggest that tumor suppressor genes involved
      in uterine carcinogenesis exist in these regions. There were no significant
      differences in frequencies of LOH between cancers of the uterine cervix and
      cancers of the uterine endometrium at any of the loci tested.

PMID- 7513542
TI  - Constitutional DNA-level aberrations in chromosome 22 in a patient with multiple
      meningiomas.
AB  - We describe a patient who developed multiple meningiomas but had no clear
      evidence of neurofibromatosis type 2. Four of the tumors, derived from three
      different sites, were analyzed cytogenetically and/or at the DNA level using
      chromosome 22 specific probes. All four tumors showed loss of the same copy of
      chromosome 22. On the chromosome that was retained in the tumors, we found two
      constitutional aberrations, a 1.5 kb deletion and a point mutation. The patient
      had inherited both alterations from her father. The father has not developed any
      meningiomas so far but he has been treated for a well-differentiated
      adenocarcinoma of the lung and a brain metastasis from this tumor. The mother and
      75 unrelated individuals did not show any of the chromosome 22 alterations. The
      multiple tumors found in the patient suggest that she has a predisposing gene for
      the development of meningiomas. The finding that all investigated tumors lost the
      same, constitutionally normal copy of chromosome 22 could indicate that the
      predisposing gene resides on chromosome 22 and was affected by the constitutional
      mutations.

PMID- 7513543
TI  - Enhanced MYCN expression and isochromosome 17q in pineoblastoma cell lines.
AB  - We have established two cell lines, PER-452 and PER-453, from an 8-month-old girl
      with an extensive pineoblastoma. Characterization of these lines revealed that
      the proto-oncogenes MYC and MYCN were not amplified, but both cell lines showed
      MYCN expression comparable to a cell line with 200-fold MYCN amplification. Both
      cell lines contained an i(17q). These results support the concept that
      pineoblastomas belong to a larger group of primitive neuroectodermal tumors of
      the central nervous system. These two cell lines provide a unique opportunity to
      investigate the molecular genetic mechanisms underlying these neoplasms further.

PMID- 7513544
TI  - Dedifferentiated chondrosarcoma with t(9;22)(q34;q11-12).
AB  - Translocation t(9;22)(q22-31;q11-12) is associated with the myxoid variant of
      chondrosarcoma. We present here a report of a patient with a dedifferentiated
      grade IV chondrosarcoma, which originated from the iliac bone and contained areas
      of grade I chondrosarcoma. There was no evidence of myxoid differentiation. The
      tumor had the karyotype 46,X,-X,t(9;22)(q34;q11-12), + mar[5]/52-61,x?,2-3
      min,inc[9]/46,XX[2]. It is possible that the different breakpoints in the t(9;22)
      may reflect different histopathologic subgroups of chondrosarcoma.

PMID- 7513545
TI  - CGG-repeat polymorphism of the BCR gene rules out predisposing alleles leading to
      the Philadelphia chromosome.
AB  - The Philadelphia chromosome (Ph) is associated with leukemia, most frequently of
      the chronic myelogenous variety. The Ph chromosome is a translocation chromosome
      which gains oncogenic potential through the fusion of the ABL oncogene of
      chromosome 9 with the BCR gene of chromosome 22. The Ph is believed to arise from
      random chromosome rearrangement with a subsequent selective advantage of the
      malignant cell line. However, alleles may be present in the population which
      predispose toward this specific rearrangement. We used a highly polymorphic CGG
      repeat polymorphism within the first exon of the BCR gene to determine BCR allele
      frequencies among 26 leukemia patients with the Ph chromosome and 63 control
      individuals. Eight BCR alleles of variable CGG-repeat length were present in both
      groups at statistically similar frequencies and in Hardy-Weinberg equilibrium. We
      therefore concluded that there are no alleles of the BCR gene that have a major
      predisposing influence on the development of the Ph chromosome and subsequent
      leukemia.

PMID- 7513546
TI  - Band 11q13 is nonrandomly rearranged in hibernomas.
AB  - Cytogenetic study of a short-term culture from a hibernoma, a very rare benign
      proliferation of the brown fat, demonstrated a four-break translocation
      t(5;7;11;17)(p14;q11.23;q13.1-13.3;p11.2) as the sole abnormality in all analyzed
      cells. Complex translocation involving band 11q13 have also been detected in the
      two other published cases of hibernoma. The consistent finding of 11q13
      rearrangements appears to distinguish hibernoma from other benign adipose tissue
      tumors cytogenetically and suggests that 11q13 changes may play an important role
      in hibernoma pathogenesis.

PMID- 7513547
TI  - Amplification of the anonymous marker D17S67 in malignant astrocytomas.
AB  - Loss of heterozygosity (LOH) for chromosome arms 9p, 10p, 10q, and 17p and
      amplification of the epidermal growth factor receptor (EGFR) gene have been
      identified as frequent genetic changes in malignant astrocytomas. We have found
      amplification of the anonymous marker D17S67 on chromosome arm 17p in 10% (3 of
      30 cases) of astrocytomas of the highest malignancy grade. The tumors with D17S67
      amplification displayed other genetic changes on chromosome 17, including
      additional amplifications and deletions. All three patients with D17S67
      amplification developed severe brain edema and died within 1 month after
      operation.

PMID- 7513548
TI  - Abnormalities of chromosome 22 in pediatric meningiomas.
AB  - Cytogenetic studies of eight meningiomas in young children or adolescents were
      performed. Two tumors exhibited normal karyotypes. Two tumors from patients with
      bilateral acoustic neurofibromatosis demonstrated monosomy 22 as the only
      abnormality. Four patients had more complicated karyotypes in which one or both
      of the chromosomes 22 were missing or structurally altered. The most common
      secondary changes in these four tumors involved monosomy or structural
      abnormalities of chromosome 6. These findings confirm that the primary
      cytogenetic changes in meningioma are similar in children and adults. Molecular
      analyses of pediatric meningiomas with deletions or translocations of chromosome
      22 will be useful for identifying the role of chromosome 22 tumor suppressor
      genes in this disease.

PMID- 7513550
TI  - Chromosome abnormalities in pancreatic adenocarcinoma.
AB  - Adenocarcinoma of the pancreas is the fifth most common cause of cancer deaths in
      the United States, yet few cytogenetic studies of this tumor have been reported.
      We analyzed 26 primary tumors to identify which chromosome abnormalities occur
      most frequently in this neoplasm. One carcinoma was well differentiated and mucin
      producing, 18 were moderately well differentiated, and seven were poorly
      differentiated. Only normal karyotypes were obtained from nine carcinomas. The
      remaining 17 carcinomas frequently had normal metaphase cells in addition to
      simple to highly complex karyotypes. The modal chromosome number in 20 carcinomas
      was diploid or near-diploid; four carcinomas had both a major near-diploid and
      near-triploid or near-tetraploid component, and two were near-tetraploid.
      Numerical abnormalities included loss of whole copies of chromosomes 6, 17, and
      18, and gains of chromosome 20. Structural abnormalities were frequent, with 1p,
      2p, 3p, 4q, 6q, 7q, 11q, and 17p recurrently involved. Results of this study were
      combined with karyotypes of 19 other primary adenocarcinomas of the pancreas
      reported in the literature. The combined data involving 117 breakpoints suggest
      that careful analysis of chromosome 20, proximal 1q, 6q, proximal 8p, and
      proximal 17p could be productive in defining genes involved in adenocarcinoma of
      the pancreas.

PMID- 7513549
TI  - Chromosome analysis of nine osteosarcomas.
AB  - Although recurrent chromosome abnormalities have been identified in several
      histologic subtypes of sarcomas, no consistent rearrangement has yet been found
      in osteosarcomas. Cytogenetic analyses of nine cases of osteosarcoma are
      reported, including seven newly diagnosed tumors and two recurrent tumors. There
      were seven high-grade osteosarcomas, one periosteal osteosarcoma, and one well
      differentiated sarcoma. All tumors were studied in short-term primary culture.
      Modal number ranged from near diploid to near triploid. Seven tumors had complex
      karyotypes with multiple structural abnormalities; two had only normal
      karyotypes. The retinoblastoma gene on chromosome 13 and the TP53 gene on
      chromosome 17 have been involved in osteosarcoma. Five tumors had loss of a whole
      copy of chromosome 13, and three of these also had a loss of a whole copy of
      chromosome 17. However, these losses were observed in the setting of numerous
      other chromosome losses. Numerous structural abnormalities were observed, many
      involving additions of unidentified material, unbalanced translocations, or
      deletions. Structural abnormalities with similar breakpoints involving 6q, 8q,
      9q, and 14p were seen in two or three tumors each. When the tumors in this series
      were added to the 18 published cases, the pericentromeric regions of chromosomes
      1, 3, and 14, and segments 6q15-21, 8q24, 9q34, 12p13, 17p13, and 19q13, were
      found to be involved in five or more structural rearrangements. Molecular
      analyses of these chromosome regions may yield genes important in the
      pathogenesis of osteosarcoma.

PMID- 7513551
TI  - Chronic inhibition of nitric oxide production accelerates neointima formation and
      impairs endothelial function in hypercholesterolemic rabbits.
AB  - To determine if endogenous local levels of nitric oxide (NO) modulate
      atherogenesis, we studied the effect of inhibiting NO with NG-nitro-L-arginine
      methyl ester (L-NAME) on early neointima formation in cholesterol-fed rabbits.
      Male rabbits were fed for 5 weeks with a 0.5% cholesterol diet alone or treated
      in addition during the last 4 weeks with L-NAME (12 mg/kg per day SC) via osmotic
      minipump. Endothelial cell function was assessed in isolated aortic rings by
      vascular reactivity and levels of cyclic GMP. In L-NAME-treated rabbits there was
      inhibition of endothelium-dependent relaxations to acetylcholine and the calcium
      ionophore A23187 as well as impaired cyclic GMP accumulation in response to
      acetylcholine. Neointima formation in the ascending thoracic aorta was assessed
      by determining media and intima cross-sectional areas with computerized image
      analysis. Compared with rabbits that consumed the cholesterol diet alone, L-NAME
      treated rabbits had significant increases in lesion area (0.29 +/- 0.04 versus
      0.15 +/- 0.03 mm2) and in lesion/media ratio (0.06 +/- 0.01 versus 0.03 +/-
      0.01). Plasma levels of cholesterol and fluorescent lipid peroxide products were
      unchanged, suggesting no difference in cholesterol metabolism or oxidation.
      Because arterial blood pressure was not altered by L-NAME treatment, the
      increased atherogenesis could not be attributed to an increase in blood pressure.
      These results indicated that local inhibition of NO accelerates early neointima
      formation possibly because of modulating monocyte recruitment or foam cell lipid
      accumulation.

PMID- 7513552
TI  - Increased expression in vivo of VCAM-1 and E-selectin by the aortic endothelium
      of normolipemic and hyperlipemic diabetic rabbits.
AB  - Atherosclerosis is enhanced in humans with diabetes mellitus, but the
      mechanism(s) involved remains unclear. Increased leukocyte-endothelium
      interaction may be involved, since mononuclear leukocyte adherence to the
      endothelium is an early event in both experimental atherosclerosis and alloxan
      induced diabetes in rabbits. In situ immunohistochemistry was used in en face
      Hautchen endothelial preparations to identify endothelial cells that stained with
      antibodies to endothelial leukocyte adhesion molecules (vascular cell adhesion
      molecule-1 [VCAM-1] and E-selectin), and the number of stained cells per 10,000
      cells was determined. Preparations from aortas of diabetic normolipemic and egg
      yolk diet-induced hyperlipemic diabetic rabbits were compared with those from
      normoglycemic animals on similar diets. Cross sections of the vessel wall were
      stained with oil red O and antibodies to VCAM-1, E-selectin, and RAM-11-positive
      macrophages. After 4 weeks of hyperlipemia the frequency of cells expressing VCAM
      1 or E-selectin was significantly increased compared with normolipemic controls;
      this frequency was further increased in the aortas of hyperlipemic diabetic
      rabbits. VCAM-1 and E-selectin expression was more frequent in normolipemic
      diabetic rabbit aortas than in hyperlipemic, normoglycemic vessels. The
      potentiation of expression of these adhesion molecules in diabetic animals may
      provide part of the explanation for the enhanced atherosclerosis associated with
      diabetes mellitus.

PMID- 7513553
TI  - Thermodynamic studies of tyrosyl-phosphopeptide binding to the SH2 domain of
      p56lck.
AB  - The interaction between SH2 domains and tyrosine-phosphorylated proteins is
      essential in several cytosolic signal transduction pathways. Here we report
      thermodynamic studies of the interaction of the p56lck (lck) SH2 domain with
      several phosphopeptides, using the technique of isothermal titration calorimetry
      (ITC). This is the first report of the use of ITC to study SH2 domain binding
      reactions. The free energy of binding of the SH2 domain of lck to a
      phosphopeptide corresponding to the autoregulatory C-terminus of the protein
      (pY505) was found to be similar to that measured for a phosphopeptide modeled on
      the C-terminus of the epidermal growth-factor receptor (delta G degrees
      approximately -7.0 kcal mol-1 at pH 6.8), although significant differences in the
      enthalpy and entropy were observed. Binding of a phosphopeptide modeled on the C
      terminus of p185neu was weaker (delta G degrees approximately -5.4 kcal mol-1 at
      pH 6.8). Lowering the pH to 5.5 reduced the binding affinity of pY505 by
      approximately 1 order of magnitude. We ascribe this to the protonation of a
      histidine side chain in the SH2 domain (H180), which is involved in a hydrogen
      bonding network that optimizes the binding site geometry. No difference in
      affinity was observed between portions of lck corresponding to the SH3-SH2
      (residues 63-228) and SH2 (residues 123-228) domains for the pY505 peptide. We
      also studied the effect upon pY505 peptide binding of mutations at two highly
      conserved arginine residues in the lck SH2 domain (R134 and R154).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7513554
TI  - Motionally restricted tryptophan environments at the peptide-lipid interface of
      gramicidin channels.
AB  - The tryptophans in the gramicidin channel play a crucial role in the organization
      and function of the channel. The localization and dynamics of these tryptophans
      have been studied using fluorescence spectroscopy, especially utilizing
      environment-induced effects on the rates of solvent relaxation around these
      residues in membranes. When incorporated into model membranes of dioleoyl-sn
      glycero-3-phosphocholine (DOPC), the tryptophans in the gramicidin channel
      exhibit a red edge excitation shift (REES) of 6 nm. In addition, fluorescence
      polarization shows both excitation and emission wavelength dependence.
      Fluorescence lifetime analysis shows a biexponential decay, corresponding to a
      short- and a long-lifetime component. The mean lifetime was found to be dependent
      on both excitation and emission wavelengths. Analysis of time-resolved emission
      spectra (TRES) shows a heterogeneous environment for the tryptophans consistent
      with the lifetime information. Taken together, these observations point out the
      motional restriction experienced by the tryptophans in the gramicidin channel.
      This is consistent with other studies in which such restrictions are thought to
      be imposed due to hydrogen bonding between the indole rings of the tryptophans
      and the neighboring lipid carbonyls. The significance of such organization in
      terms of functioning of the channel is brought out by the fact that substitution,
      photodamage, or chemical modification of these tryptophans is known to give rise
      to channels with conformation and reduced conductivity.

PMID- 7513555
TI  - Molecular recognition of a Salmonella trisaccharide epitope by monoclonal
      antibody Se155-4.
AB  - The binding site of monoclonal antibody Se155-4, which has been the object of
      successful crystallographic and antibody-engineering studies, is shown by solid
      phase immunoassays to be complementary to a branched trisaccharide, alpha-D
      Galp(1-->2) [alpha-D-Abep(1-->3)]-alpha-D-Manp(1, rather than to the
      tetrasaccharide repeating unit alpha-D-Galp(1-->2) [alpha-D-Abep(1-->3)]-alpha-D
      Manp(1-->4) alpha-L-Rhap(1- of the bacterial antigen. Specificity for the 3,6
      dideoxy-D-xylo-hexose (3,6-dideoxy-D-galactose) epitope present in Salmonella
      paratyphi B O-antigens was ensured by screening hybridoma experiments with
      glycoconjugates derived from synthetic oligosaccharides. Detailed epitope mapping
      of the molecular recognition by modified and monodeoxy oligosaccharide
      derivatives showed that complementary surfaces and three antibody-saccharide
      hydrogen bonds are essential for full binding activity. Both hydroxyl groups of
      the 3,6-dideoxy-D-galactose residue were obligatory for binding and consistent
      with the directional nature of their involvement in carbohydrate-protein hydrogen
      bonds; related tetrasaccharides built from the isomeric 3,6-dideoxyhexoses, 3,6
      dideoxy-D-glucose, paratose, and 3,6-dideoxy-D-mannose, tyvelose were not bound
      by the antibody. Titration microcalorimetry measurements were consistent with the
      hydrogen-bonding map inferred from the crystal structure and suggest that the
      displacement of water molecules from the binding site accounts for the favorable
      entropy that accompanies binding of the native trisaccharide determinant. The
      protein sequences determined for the antibody VL and VH domains reveal somatic
      mutation of the VL germ line gene, implying that this antibody-binding site
      results from a mature antibody response.

PMID- 7513556
TI  - Effects of DsbA on the disulfide folding of bovine pancreatic trypsin inhibitor
      and alpha-lactalbumin.
AB  - DsbA is a protein found in the periplasm of Escherichia coli that is required for
      the formation of disulfide bonds in secreted proteins. It contains only two
      cysteine residues, which can form reversibly a very unstable disulfide bond that
      has been proposed to be the oxidant that introduces disulfide bonds into secreted
      proteins. The present study investigates the effect of DsbA on the well
      characterized disulfide-coupled refolding processes of BPTI and of alpha
      lactalbumin. Disulfide-bonded DsbA in stoichiometric amounts proved to be a very
      potent donor of disulfide bonds to reduced BPTI but showed little catalytic
      activity at neutral pH in the presence of a glutathione redox buffer. In contrast
      to the related eukaryotic enzyme protein disulfide isomerase, DsbA did not
      substantially catalyze the usual intramolecular disulfide bond rearrangements of
      quasi-native folding intermediates of BPTI. Neither did DsbA catalyze the
      intramolecular rearrangements observed in the three disulfide-bonded "molten
      globule" form of alpha-lactalbumin at neutral pH. Thiol-disulfide exchange is
      normally very slow at acidic pH but occurs rapidly with DsbA; consequently, DsbA
      catalyzed the disulfide folding of BPTI under acidic conditions. It was then
      possible to detect some increase in the rates of disulfide rearrangements, but
      only with stoichiometric amounts of DsbA and on the hour time scale. These
      results suggest that the primary role of DsbA in the bacterial periplasm is to
      introduce disulfide bonds into newly secreted proteins.

PMID- 7513557
TI  - Sequence specific thermodynamic and structural properties for DNA.RNA duplexes.
AB  - DNA.RNA hybrid duplexes are found in many important biological processes and are
      involved in developing modes of disease treatment, such as antisense therapy, yet
      little is known about the sequence dependence of their structure and stability.
      The structure and thermodynamic stability of DNA.RNA hybrid model systems
      corresponding in composition and length and containing (1) all purine or all
      pyrimidine bases on each strand or (2) mixed purine and pyrimidine bases on each
      strand have been evaluated relative to pure RNA and DNA duplexes by thermal
      melting, CD, and electrophoresis analyses. The spread in free energies of
      denaturation of the homopurine.homopyrimidine systems covers over 14 kcal/mol of
      single strands, while the mixed sequence free energies vary by less than 4
      kcal/mol. The RNA-homopurine.DNA-homopyrimidine hybrid resembles a corresponding
      pure RNA duplex in both structure and stability, whereas the DNA-homopurine.RNA
      homopyrimidine hybrid resembles a corresponding pure DNA duplex. The mixed
      sequence hybrids show intermediate structure between the corresponding pure RNA
      and pure DNA duplexes and a stability closer to that of the pure DNA duplex. From
      these results and the evaluation of published hybrid data [Hall, K. B., &
      McLaughlin, L. W. (1991) Biochemistry 30, 10606-10613; Roberts, W. R., &
      Crothers, D. M. (1992) Science 258, 1463-1466], it can be predicted that a hybrid
      duplex containing more RNA purine bases will have a CD spectrum, and probably
      conformation, resembling that of A-form duplexes and will be more stable than a
      corresponding hybrid duplex with fewer RNA purine bases.

PMID- 7513558
TI  - Reaction of DNA-bound ferrous bleomycin with dioxygen: activation versus
      stabilization of dioxygen.
AB  - The properties of binding of dioxygen to ferrous bleomycin [Fe(II)Blm] in the
      presence of DNA have been examined. Dioxygen reacts rapidly with Fe(II)Blm.DNA,
      forming an adduct that is increasingly stable to oxidation-reduction as the ratio
      of base pairs to drug becomes larger. This species has a spectrum similar to that
      reported for a proposed dioxygenated intermediate in the solution reaction of
      Fe(II)Blm with O2. It contains Fe(II) as measured with bathophenanthroline
      disulfonate (BPS) and O2 according to direct observation of stoichiometric
      release of O2 upon chelation of Fe(II) by BPS. The dioxygenated form O2
      Fe(II)Blm.DNA, is highly stable; bound O2 dissociates upon purging with N2 with a
      rate constant of 0.16 min-1. Although Fe(II)Blm or Fe(II)Blm.DNA reacts almost
      completely with BPS within the time of mixing, O2-Fe(II) Blm.DNA reacts much
      slower in a process that is first order in Fe(II) and in BPS at constant DNA
      concentration. The rate is inversely related to DNA concentration reaching a
      limiting value at 50-100 base pairs per drug molecule. The kinetics of oxidation
      of Fe(II)Blm bound to DNA by O2 are biphasic and depend on the base pair to drug
      ratio. After formation of O2-Fe(II)Blm.DNA, another reaction occurs in which O2
      is released, which is second order in dioxygen donor, and in which the second
      order rate constant declines with increasing base pairs to FeBlm ratio. The rate
      of this second-order process accelerates at higher ionic strength.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7513559
TI  - Inhibition of the actions of palytoxin on the K+ efflux from red cells and on the
      Na/K-ATPase activity by a monoclonal antibody.
AB  - Palytoxin (PTX) binds to the Na/K pump, inhibits the (Na/K)-ATPase and forms Na
      and K permeable channels in human red cells. Here, we report that a monoclonal
      antibody raised against a derivative of PTX (Bignami, G.S. et al. (1992) Toxicon
      30, 687-700) inhibits these effects. The observations are consistent with a model
      in which (a) the antibody binds and, thus reduces the concentration of free PTX
      available to react with the Na/K pump, and, (b) the PTX-antibody complex also
      binds to the PTX receptor on the Na/K pump but in such a way that a cation
      permeable channel is not formed, probably by reducing the concentration of free
      PTX. Using this model, we estimate that the apparent dissociation constant for
      the binding of PTX to antibody is 0.2 nM.

PMID- 7513562
TI  - [Computed tomography of the abdominal lymphomas in Whipple's disease].

PMID- 7513561
TI  - [The palliative treatment of venous stenoses in tumor patients with self
      expanding vascular prostheses].
AB  - During 53 months 14 patients with tumour-induced obstructions of the superior
      vena cava (n = 8), the inferior vena cava (n = 2) and iliac veins (n = 4) were
      treated with self-expandable metallic stents. 21 Wall stents and 5 Gianturco
      double stents were applied. The follow-up lasted from 2 weeks to 16 months (range
      = 5.7 months). All patients showed a marked relief of inflow obstruction after
      stent placement. 6 of 7 patients, who died of their disease during follow-up,
      were asymptomatic regarding vein obstruction until their death (3 weeks to 16
      months). In 6 of 7 still living patients no re-obstruction occurred during follow
      up (2 to 16 months). Patency rate was 82%. These results suggest that self
      expanding stents are a successful palliative therapy of malignant vein
      obstructions.

PMID- 7513563
TI  - Interaction between FK506 and erythromycin.

PMID- 7513560
TI  - [The chemoembolization of hepatocellular carcinoma: the computed tomographic
      findings and clinical results in prospective repetitive therapy].
AB  - Between April 1989 and March 1993 162 transarterial chemoembolizations (TACE)
      were performed repeatedly (mean interval: 2.9 months) in 52 patients with
      hepatocellular carcinoma (HCC): An emulsion of Lipiodol and epirubicin was
      injected as selectively as possible in a dosage proportional to liver function
      and tumour size. Before and after each TACE the size of tumours and ratio of
      tumour volume containing Lipiodol (RTVCL) were determined in CT and the grade of
      tumour vascularisation was assessed angiographically. The RTVCL increased from
      58% after the first treatment to 73% after the third treatment. RTVCL and
      Lipiodol retention were higher in responders than in non-responders. Tumours with
      expansive growth pattern showed a higher response rate (56%) than infiltrating
      tumours (20%). Mean survival of these patients was different (19 and 8 months; p
      < 0.01), respectively. Survival rates of all patients were 54, 22, and 11% after
      1, 2 and 3 years, respectively. Repeated TACE shows local effectiveness. Three
      treatments during a period of one year are recommended for patients with Child
      Pugh class A cirrhosis.

PMID- 7513565
TI  - Production of human p53 specific monoclonal antibodies and their use in
      immunohistochemical studies of tumor cells.
AB  - We describe the production of 13 new monoclonal antibodies induced by the product
      of the human p53 tumor suppressor gene. All these monoclonal antibodies recognize
      human p53 irrespective of the detection technique: ELISA, immunoblot or
      immunoprecipitation. These antibodies can be divided into four groups according
      to such criteria as localization of the recognized epitopes and reactivity with
      p53 originating from other organisms. One monoclonal antibody was successfully
      used for immunohistochemistry detection of p53 accumulation in breast carcinoma.
      This novel panel of monoclonal antibodies represents a further tool for the study
      of the p53 protein.

PMID- 7513564
TI  - A transient increase of phenylalanine ammonia-lyase transcript in kinetin-treated
      tobacco callus.
AB  - In tobacco cell culture (Nicotiana tabacum L. "Bright Yellow" T-13),
      phenylalanine ammonia-lyase (PAL) activity was induced in response to an
      exogenously added kinetin. RNA blot hybridization analysis showed that a single
      species of PAL transcript 2.9-kb in size was detected using the PAL cDNA cloned
      from kinetin-treated cells. The cellular content of this transcript increased
      transiently (2.5-fold) 4 h after the addition of kinetin followed by an increase
      in PAL enzyme activity at 16 h.

PMID- 7513566
TI  - [Iatrogenic fibrosis in cancerology (2): main etiologies and therapeutic
      possibilities].
AB  - Fibrosis in oncology concerns iatrogenic pathology, after radiotherapy or
      bleomycin, and also after surgery or neoadjuvant chemotherapy. Specificity of
      certain etiologic conditions are described in detail. Some therapeutic attitudes
      are discussed. Corticoids are useful in the management of inflammatory fibrosis
      attacks. Other drugs under study are used in an attempt to reduce the late
      fibrotic process, namely liposomal superoxide dismutase.

PMID- 7513567
TI  - Action potentials, calcium transients and the control of differentiation of
      excitable cells.
AB  - Calcium influx via action potentials in differentiating nerve and muscle is
      regulated principally by the expression of potassium currents. Transient
      elevations of intracellular calcium in spontaneously active cells are necessary
      for normal neuronal development. The mechanisms that connect calcium elevations
      to long term developmental change are likely to be utilized in the mature nervous
      system.

PMID- 7513568
TI  - Experimental regeneration in canine muscular dystrophy--2. Expression of myosin
      heavy chain isoforms.
AB  - The sequential expression of neonatal, fast and slow myosin heavy chain isoforms
      was examined during the regeneration of normal and dystrophic dog muscle from 1
      to 56 days, following necrosis induced by the venom of Notechis scutatis, to
      assess the regenerative potential of dystrophic muscle. Regeneration was equally
      rapid in normal and dystrophic dogs but morphological and immunocytochemical
      abnormalities were more apparent in the dystrophic fibres. New myotubes were
      formed by 3 days, and by 4 days all myosin isoforms were expressed. Neonatal
      myosin persisted in normal dogs after morphological restoration of the muscle and
      after dystrophin and beta-spectrin expression had returned to normal. Neonatal
      myosin was considerably reduced by 21 days in normal dogs, but persisted beyond
      28 days in dystrophic dogs, suggesting a delay in maturation. At 42 and 56 days,
      dystrophic dogs showed a population of small fibres expressing neonatal myosin,
      which may represent a second cycle of degeneration and regeneration. The
      reciprocal pattern of fast and slow myosin was not fully restored in normal or
      dystrophic regenerating muscle, and co-expression persisted. Thus, dystrophic
      muscle retains its potential to regenerate, but maturation is slower than normal.
      The persistent co-expression of isoforms has implications for the long-term
      function of fibres formed after myoblast therapy, but the results imply that a
      stable state can be achieved if dystrophin expression is restored by gene or
      myoblast transfer therapy.

PMID- 7513571
TI  - [Ultrastructural aspects of cross adaptation to cold and altitude hypoxia].
AB  - Prolonged cold and altitude exposures were examined for their impact on the
      ultrastructure of the albino rat diaphragm and liver. The ultrastructural
      analysis of the respiratory muscle and liver showed their structural response
      differences under these conditions. There was a substantial rise in mitochondrial
      and lipid droplet volume densities and maintenance of glycogen stores in the
      muscle fibers at the end of the experiment. The hepatocyte mitochondrial
      responses were similar, but less pronounced and slower. The glycogen and plastic
      reserves of hepatocytes were reduced. This provides evidence for that the
      adaptive process is less effective in the hepatocytes than in the muscle under
      these conditions. At the same time the lack of structural disturbances in the
      muscle fibers and hepatocytes during prolonged altitude and cold exposures may be
      considered as the evidence of the stabilizing influence of the latter factor, its
      protective role in the cross-adaptation mechanisms.

PMID- 7513570
TI  - [Ecologic problems of contemporary psychiatry: regional aspects].

PMID- 7513572
TI  - [Effect of diet on the biochemical parameters of blood in the population of the
      Asian North].
AB  - The studies have shown that the diet of the native residents of Taimyr is
      imbalanced of the major nutrients (high uptake of carbohydrates and low uptake of
      fats and proteins). A certain correlation has been found between the higher
      incidence rates of coronary heart disease, blood atherogenic lipoprotein levels
      and changed diet pattern.

PMID- 7513573
TI  - [Adaptive and non-adaptive reactions of vision in the Far North].
AB  - The paper deals with the study of specific features of ocular adaptive reactions
      under the conditions of the Far North. The author suggests that there should be 3
      types of ocular adaptation in the North: (1) and (2) being at the individual
      level and (3) at the population level. Type 1 adaptation is usually observed
      within the first months of stay in the North. The ocular status of newcomers is
      characterized by lower hydrodynamic parameters: a tendency to intraocular
      vascular dystonia (the hypertensive type) is formed. Type 2 adaptation is
      generally seen after spending 10 years of stay in the North. Persistent
      physiological vascular reactions are formed (within the upper normal range).
      Organic disadaptive changes in microvasculature develop in a third of the new
      residents in the North. Type 3 hereditary long-term adaptation is observed in the
      indigenous residents of the North. The most optimum ratios of hemo- and
      hydrodynamic parameters along with definite changes in anatomic and functional
      indices form in them, which is reflected in the specific features of eye
      diseases.

PMID- 7513574
TI  - [Endoscopic and morphologic characteristics of the gastric mucosa in children of
      the Far North].
AB  - The epidemiological studies in Evenkia and Yakutia have revealed children with
      gastroduodenal abnormalities. The endoscopic examination has shown that that
      there is a prevalence of superficial gastritis in Evenkia and hypertrophic
      gastritis in Yakutia, the histological studies have found no substantial
      differences. Gastroduodenal reflux was recorded in Evenk children more
      frequently, in 51.7% it was accompanied by lymphoid cell infiltration in the
      intrinsic mucosal plate.

PMID- 7513569
TI  - [Psychophysiologic predisposing factors of health disturbances in workers of
      various shifts in Northern expeditions].
AB  - It has been shown that the mental status of the body determines the direction of
      psychophysiological and somatic adaptation of the workers of industrial North
      expeditions. This should be taken into account while predicting the risk and
      development of diseases and their prevention.

PMID- 7513575
TI  - [Rationale for alcohol consumption and mitochondrial aldehyde dehydrogenase
      genotype in the native male population of Chukotka].
AB  - To study the alcohol consumption pattern and mitochondrial aldehyde dehydrogenase
      (ALDH2) genotype, a random sample consisting of 170 native males (Chukchee and
      the Eskimo), residents of 4 Chukotka settlements, was studied. According to
      interviews, most residents (68%) consumed alcohol once or twice a month; however
      during an alcohol uptake episode they consumed very high (intoxicating) doses
      exceeding 150 g of pure alcohol. The rates of control loss, alcohol amnesia and
      withdrawal syndrome were more than 50%. Twelve per cent reported inconsistent
      facial flushing after drinking and positive ethanol-patch test was found only in
      2% of cases. Direct genotyping, using specific oligonucleotide probes, showed no
      atypical oriental type ALDH2. The normal genotype (ALDH2-1) was present in all
      the examinees from Chukotka natives (n = 87). These results explain the ability
      of Chukotka natives to consume high amounts of alcohol per occasion and they are
      in disagreement with the hypothesis that the drinking pattern among the natives
      is explained by specific features of alcohol-metabolising enzymes.

PMID- 7513576
TI  - [Assessment of health status of the population in the Northern regions (based on
      data from West-Yakutsk industrial region)].
AB  - There is a prevalence of chronic diseases over acute ones among adults and
      children who have come to Yakutia. There is a high association of inflammatory
      and non-inflammatory diseases and changes in the disease pattern, age, and stay
      duration in the North. Some common pathologic syndromes have been found to affect
      the development of chronic diseases. The common character of risk factors for
      various diseases developing in the newcomers in the North serves as the basis for
      establishing united programmes on their multifactorial prophylaxis whose ultimate
      goal is to prevent the occurrence and unfavorable course of etiologically and
      pathogenetically related diseases.

PMID- 7513577
TI  - [Hereditary deficiency of alpha 1- antitrypsin in rats due to evolving chronic
      lung pathology].
AB  - W/SSM rats which are characterized by hereditary abnormal changes in the lungs,
      hepato- and splenomegalia and some other disturbances have also alpha 1
      antitrypsin (AAT) deficiency. A study of AAT in these rats by means of
      isoelectrofocusing and immunoblotting with anti-AAT antibodies labelled with
      peroxidase has demonstrated that deficiency of the protease inhibitor is not
      associated with any disturbances of its synthesis or any changes of its
      electrophoretic properties. A higher activity of lysosomal glycosidases and
      proteinases was found in the liver and leukocytes of W/SSM rats. It is suggested
      that AAT deficiency is due to its modification under the influence of lysosomal
      enzymes. The described biochemical distances seem to be associated with an
      increased hexose transport into the cells, which is controlled by a mutant gene.

PMID- 7513578
TI  - [Mechanisms of hyperventilation in the population of the North].

PMID- 7513580
TI  - [Neurophysiologic mechanisms of ecologic stability: forecasting and biorhythm
      correction].

PMID- 7513579
TI  - [Role of neuropeptides in the lateralization of brain (as exemplified by behavior
      in radial maze].
AB  - The effects of thyroid-releasing hormone (TRH) and substance P (SP) on rat brain
      lateralization have been studied by three test methods: T-maze, 12-arm radial
      maze (r. m.) and rotometry. The animals were given 415 micrograms/kg of TRH i. p.
      or 25 micrograms/kg of TRH intranasally or 50 micrograms/kg of SP i. p. The
      number of errors and time of task solution in r. m. decreased in the first day of
      TRH administration. Simultaneously, left-sided deviations in maze-arm choices
      appeared in some rats' strategy, which made successive arm choices possible. SP
      induced search activity in rats at the stage of acquisition, yet SP given in the
      period of tolerant r. m. performance caused degradation of short-time memory and
      right-sided lateralization appeared.

PMID- 7513581
TI  - [Mathematical modeling of physiologic processes: evolution of approaches to the
      study of goal-oriented activity of living organisms].

PMID- 7513582
TI  - [Nonsteroidal antiinflammatory agents as modulators of glucocorticoid function of
      receptors].
AB  - The modulating effect of nonsteroidal antiinflammatory drugs (analgin,
      amidopyrine, sodium salicylate) on the function of types II and III
      glucocorticoidal receptors of cytosol in the Wistar rat liver was studied by
      Scatchard's and Laynuiver-Bark's analyses and dissociation rate constants for
      steroid-receptor complexes, by using natural and artificial glucocorticoids
      having a high specific activity. Analgin was not competitive in inhibiting the
      function of type II glucocorticoid receptors, decreased the association constant,
      increased the dissociation rate constant and reduced the elimination half-life of
      the labelled triamcinolone acetonide from the receptor. The density of type III
      glucocorticoidal receptors was many times increased with analgin. Amidopyrine had
      no noticeable effect on the function of type II glucocorticoidal receptors,
      however, repeatedly enhanced the density of type III glucocorticoidal receptors.
      Sodium salicylate was not competitive in suppressing the function of type II
      glucocorticoidal receptors and increased the number of sites of binding 3H
      corticosterone to type III glucocorticoidal receptors. The latter fact can
      explain the mechanism of action of these drugs.

PMID- 7513583
TI  - [Testing of plant extracts preparations for prevention and non-toxic therapy of
      oncologic diseases in experimental models].
AB  - The extracts from Panax ginseng and Rhodiolae rosea from natural roots, from
      cultural callus tissue and from Ganoderma mushroom have been studied for
      adaptogene, T-immunogene activities and for stimulation of mechanical integration
      in tissues predisposed to hereditary tumors. The least activity has been shown by
      extracts from Ganoderma M., that from Rhodiolae rosea natural root has turned out
      to the most effective. This study can serve as the basis for further
      investigations by using the extracts on inbred mice and in the clinical setting
      for the prevention and intoxic therapy of tumors.

PMID- 7513585
TI  - Quantitation of specific transcripts by RT-PCR SNuPE assay.

PMID- 7513584
TI  - [Medico-ecologic and technologic problems of health promotion in the population
      of Siberia].
AB  - The comprehensive investigations have demonstrated that environmental factors
      have an unfavourable influence on children's morbidity rates of cancer and
      congenital diseases. A mechanism has been proposed to solve medical, ecological,
      and technological problems of public health population.

PMID- 7513586
TI  - An efficient polymerase chain reaction approach for the quantitation of multiple
      RNAs in human tissue samples.
AB  - We describe a PCR quantitation approach that we have set up to study gene
      expression in human skeletal muscle biopsies. It is characterized by the
      independent standardization of the individual steps and ignores attempts to
      control for the efficiency of the PCR. Different RNA extraction/reverse
      transcription efficiencies are normalized by the addition of an unrelated cRNA.
      Quantitation is achieved by parallel amplifications of reference samples
      containing known amounts of PCR products. Precision was achieved by multiple
      measurements of several samples. Our approach allows for the detection of less
      than twofold differences (27-88%, depending on the RNA species studied) among
      samples. A comparison of biopsies from highly trained endurance runners with
      biopsies from untrained subjects showed that the increased mitochondrial density
      in the runners' samples is accompanied by a proportional increase in the
      concentration of the mRNA of cytochrome c oxidase subunit IV.

PMID- 7513587
TI  - Minimizing effects of low literacy on medication knowledge and compliance among
      the elderly.
AB  - Medication knowledge and compliance among the elderly was examined using a color
      coded method, which was designed to tailor the medication regimen to the person's
      daily schedule. Data were collected from 80 elderly, predominantly indigent, and
      individuals of low literacy. Group 1 of the study received verbal teaching only,
      whereas Group 2 received verbal teaching and a color-coded medication schedule.
      Knowledge increased significantly among both groups. Compliance to the medication
      schedule increased in Group 2, among those subjects whose pretest compliance
      scores were low. These results suggest that a method that considers the
      characteristics of the individual can significantly increase knowledge and
      compliance.

PMID- 7513588
TI  - Suppression of the antivenom antibody response by serum therapy.
AB  - 1. The antivenom antibody response of mice injected with Bothrops jararaca venom
      and receiving specific serum therapy was studied under different experimental
      conditions. Balb/c mice (18-22 g) injected with venom (1.75 mg/kg) presented the
      clinical symptoms observed in patients bitten by B. jararaca and a high and long
      lasting antivenom antibody response. 2. Injection of 0.1 ml of horse antiserum to
      venom 15 min after venom administration abolished the symptoms induced by the
      venom and induced an almost completely suppressed production of mouse antivenom
      antibodies. The extent of suppression of the antivenom antibody response depended
      on the dose of horse antiserum administered and was greater the sooner the serum
      therapy was applied after envenomation. 3. Injection of antiserum into envenomed
      mice that received an unrelated antigen (KLH) did not suppress the antibody
      response to KLH antigen though it inhibited production of antivenom antibodies.
      4. Envenomed mice receiving an equivalent dose of F(ab')2 fragments obtained by
      pepsin digestion of horse antiserum presented the same extent of suppression of
      the antivenom antibody response as mice injected with the non-treated antiserum.
      5. Mice whose antibody response was suppressed, when rechallenged with venom,
      presented a primary antibody response. 6. These results suggest that suppression
      of the antivenom antibody response presented by envenomed patients submitted to
      serum therapy is due to the masking of the venom epitopes by horse antibodies as
      well as to the rapid elimination of the venom epitopes.

PMID- 7513589
TI  - Protection and suppression of the humoral immune response in mice mediated by a
      monoclonal antibody against the M epitope of Brucella.
AB  - The capacity of the BmE10-5 monoclonal antibody (mAb), with specificity for the
      Brucella spp. M epitope, to confer protection against infection with B. abortus
      2308 (A-dominant strain) has been evaluated. Injected before infection, the BmE10
      5 mAb diminished the bacterial counts in spleen from week 1 to week 8
      postinfection and in liver from week 4 to week 7. Thus, protection mediated by
      the BmE10-5 mAb, as measured by a reduction in the bacterial counts in both
      spleen and liver, was demonstrated from week 2 to week 8 postinfection. The
      humoral immune response of IgG, IgM, IgG1 and IgG3 antibodies, specific against
      the B. abortus 2308 smooth lipopolysaccharide, was clearly suppressed in all the
      mice protected with the BmE10-5 mAb, thus demonstrating the importance, in
      protecting against infection, of the existence in serum of M-epitope-specific
      antibodies at the same time the infection is acquired. The development of
      subcellular vaccines including the Brucella M epitope could constitute an
      interesting alternative to attenuated living vaccines.

PMID- 7513590
TI  - Virulence factors of Burkholderia cepacia.

PMID- 7513591
TI  - Immunochemical studies of opsonic epitopes of the lipopolysaccharide of
      Leptospira interrogans serovar hardjo.
AB  - Leptospiral lipopolysaccharides (LPS) are the main antigens responsible for
      immunity in leptospirosis. In this investigation we studied the nature of the
      antigenic determinants of LPS extracted from Leptospira interrogans serovar
      hardjo (reference strain Hardjoprajitno). The reactions of anti-LPS monoclonal
      antibodies (mAbs) MUM/F1-4/hardjo (IgM) and MUM/F1-6/hardjo (IgG) with whole cell
      lysates in Western immunoblotting analysis were unaffected by proteinase K
      treatment. Periodate treatment of the LPS destroyed the binding of MUM/F1
      6/hardjo but preserved that of MUM/F1-4/hardjo. Alkaline phosphatase decreased
      significantly the binding of MUM/F1-4/hardjo to the LPS but only slightly that of
      MUM/F1-6/hardjo. On the other hand, phosphodiesterase totally destroyed the
      binding capacity of both monoclonal antibodies in enzyme immunoassays (EIA). A
      number of mono- and oligosaccharides was used in EIA inhibition studies. Mannose
      6-phosphate and galactose-6-phosphate inhibited the binding of MUM/F1-4/hardjo
      (50% inhibition at a concentration of 5 mM) to the antigen, but glucose-6
      phosphate did not. Galactosamine and mannosamine inhibited the binding of MUM/F1
      6/hardjo (50% inhibition at a concentration of 3-4 mM), whereas only a weak
      inhibition was observed with glucosamine. In contrast, N-acetylated amino sugars
      did not show any inhibition. An O-acetyl group also appears to be involved in the
      antigen-antibody binding process.

PMID- 7513592
TI  - Medical-surgical nurses' utilization of research methods and products.
AB  - The purpose of this study was: (a) to describe the self-reported use of the
      methods and products of research by medical-surgical nurses, and (b) to identify
      attitudes toward the use of research-based knowledge in clinical nursing
      practice. Two hundred and twelve registered nurses completed the Research
      Utilization Questionnaire. Survey results indicated that it was difficult for
      respondents to change practice based on research. Nurses were willing to
      participate in research if investigations were relevant to practice. Articles
      from nursing research journals were ranked low by the respondents as sources of
      knowledge, while information gained from individual patients was ranked high.

PMID- 7513593
TI  - Circulating adhesion molecules in asthma.
AB  - There is increasing evidence that leukocyte-endothelial adhesion molecules are
      important in inflammatory airway disease because of their involvement in the
      primary steps of entrapment and migration of leukocytes to the site of
      inflammation. Recently, circulating forms of these adhesion molecules have been
      described, although their origin, fate, and function are still unknown. We have
      used an antigen capture ELISA to measure the concentrations of circulating
      intercellular adhesion molecule-1 (cICAM-1), E-selectin (cE-selectin), and
      vascular cell adhesion molecule-1 (cVCAM-1) in the peripheral blood of 13 atopic
      and 16 non-atopic normal subjects, 29 patients with stable asthma, and inpatients
      with acute asthma on Day 1 (n = 38), Day 3 (n = 29), and Day 28 (n = 13) of an
      asthmatic episode. Circulating ICAM-1 and E-selectin levels were significantly
      raised in acute asthma on all three study days when compared with those observed
      in stable asthma, atopic normal, or nonatopic normal volunteers with no
      significant differences among the latter three groups. Circulating VCAM-1 was not
      significantly increased in any of the groups studied. There were no correlations
      among the concentrations of these three circulating adhesion molecules. The
      elevated concentrations of cICAM-1 and cE-selectin in acute asthma may reflect
      the extensive inflammatory response occurring in the airways during acute
      exacerbations of the disease with airway obstruction. It is possible that the
      cytokine and mediator profiles in acute asthma lead to the preferential synthesis
      and expression of these two circulating adhesion molecules in comparison with
      cVCAM-1.

PMID- 7513594
TI  - In vivo characterization of the tachykinin receptors involved in the direct and
      indirect bronchoconstrictor effect of tachykinins in two inbred rat strains.
AB  - Three receptors for the tachykinins, NK1, NK2, and NK3, have been defined
      pharmacologically and have been cloned. We previously demonstrated that in Fisher
      344 (F344) rats neurokinin A (NKA) and substance P (SP) cause bronchoconstriction
      mainly by indirect mechanisms that involve both cholinergic nerves and mast
      cells. Preliminary results suggested that in a less responsive strain, the BDE
      strain, tachykinins did not activate airway mast cells. We have now compared in
      F344 and BDE rats the airway effects of the tachykinins SP and NKA with those of
      specific NK1 and NK2 receptor agonists and have studied the effect of potent and
      specific nonpeptide NK1 and NK2 receptor antagonists on NKA-induced airway
      effects. Lung resistance (RL) and serotonin in bronchoalveolar lavage fluid (BAL
      5HT) were measured in anaesthetized, mechanically ventilated, rats. In contrast
      to F344 rats, BDE rats were less sensitive to SP and NKA challenge, and no
      subsequent increase in BAL 5HT was observed. In F344 rats, the specific NK1
      receptor agonists, [Sar9, Met(O2)11]SP and Ac[Arg6,Sar9,Met(O2)11]SP(6-11),
      caused a dose-dependent bronchoconstriction and increase in BAL 5HT comparable to
      those of NKA and SP. The NK1 receptor agonists had no effect in BDE rats. The NK2
      receptor agonist [beta Ala8]NKA(4-10) caused a small, dose-dependent increase in
      RL in the F344 as well as in the BDE rat, but it had no effect on BAL 5HT. The
      NK1 receptor antagonists RP 67580 and CP 96,345 significantly reduced the
      increase in RL and BAL 5HT caused by NKA in the F344 rat, but they had no effect
      on the NKA-induced bronchoconstriction in the BDE rat.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7513595
TI  - Capsaicin-induced airway obstruction in tracheally perfused guinea pig lungs.
AB  - The neurokinin receptors responsible for transducing the airway obstruction
      resulting from capsaicin infusion were defined in the tracheally perfused guinea
      pig lung. In this lung preparation, buffer is perfused via the trachea and
      allowed to exit the lung through numerous small holes in the pleural surface;
      airway obstruction is monitored as the backpressure (Pao) generated at a constant
      perfusion flow rate. Infusion of the specific NK1 receptor agonist, Sar-9
      Met02(11) substance P, resulted in an increase in Pao; this effect was prevented
      by the NK1 receptor antagonist CP 99,994 but not by the NK2 receptor antagonist
      SR 48,968. Infusion of the specific NK2 receptor agonist Nle10-neurokinin A 4-10
      resulted in an increase in Pao; this effect was prevented by the NK2 receptor
      antagonist SR 48,968 but not by the NK1 receptor antagonist CP 99,994. In the
      absence of NK receptor antagonists, infusion of capsaicin resulted in a
      significant increase in Pao, 31 +/- 4 cm H2O. In the presence of the NK1 receptor
      antagonist, the capsaicin response was not diminished, but in the presence of the
      NK2 receptor antagonist, the Pao response diminished to only 10 +/- 2 cm H2O, p <
      0.001. These data indicate that when capsaicin is presented to the epithelial
      surface of the lung the resulting airway obstruction is mediated predominantly by
      NK2 receptor stimulation.

PMID- 7513596
TI  - Granulocyte colony-stimulating factor exacerbates acute lung injury induced by
      intratracheal endotoxin in guinea pigs.
AB  - The effects of recombinant human granulocyte colony-stimulating factor (rG-CSF)
      on the lung injury induced by intratracheal endotoxin were studied using guinea
      pigs. Animals were divided into four groups: (1) saline control, (2) endotoxin
      alone, (3) cyclophosphamide (CPA)+endotoxin, and (4) CPA+rG-CSF+endotoxin. CPA
      was injected intraperitoneally to suppress hematopoietic function 7 d before the
      study. rG-CSF at a dose of 100 micrograms/kg was administered subcutaneously
      twice a day for 5 consecutive d beginning 2 d after the CPA pretreatment. Saline
      or 0.2 mg/kg of endotoxin was administered via the airway, and the animals were
      observed for 4 h. 99mTc-labeled macroaggregated albumin was mixed with saline or
      endotoxin to obtain a lobar distribution. Lung injury was assessed by the
      concentration ratio of 125I-labeled albumin in lung tissue to plasma (T/P) and
      lung wet-dry weight ratio (W/D). We also counted the number of neutrophils in
      bronchoalveolar lavage (BAL) fluid and fixed lung tissues. T/P, but not W/D,
      increased in endotoxin-alone and CPA+endotoxin groups compared with the saline
      control group (p < 0.01). Both T/P and W/D of the CPA+rG-CSF+endotoxin group were
      significantly higher than those of the endotoxin-alone and CPA+endotoxin groups
      (p < 0.01). In the CPA+rG-CSF+endotoxin group, histopathologic examination of the
      lung sections showed neutrophil recruitment into the lung, and neutrophil counts
      in BAL fluid were elevated. In conclusion, pretreatment with rG-CSF increased
      sequestration of neutrophils into the lung and exacerbated the lung injury
      induced by intratracheal endotoxin in CPA-treated guinea pigs.

PMID- 7513598
TI  - Mechanisms of processing and presentation of the antigens of Listeria
      monocytogenes.
AB  - Antigen processing is the series of events through which protein antigens become
      degraded and are sent to the cell surface for recognition by T cells. These
      events within the cell have been studied extensively using the model system of
      infection with Listeria monocytogenes. This bacteria resides primarily
      intracellularly; immunity to it is mediated by cellular responses. Upon
      phagocytosis by a macrophage, engulfed Listeria express a hemolytic molecule,
      listeriolysin O (LLO), and can disrupt the membrane of the endosome and escape
      into the cellular cytoplasm. This allows the organism to escape the hostile
      environment of the endosome and also gives it access to the processing machinery
      of the cytoplasm. Therefore, Listeria monocytogenes can be processed within an
      endosome and be presented by class II MHC, or can escape into the cytoplasm and
      be processed there and presented by class I MHC. This LLO molecule is not only an
      important virulence factor, it is also a dominant antigen in the cellular immune
      response to Listeria. The outcome of antigen processing and presentation can be
      influenced by the expression of LLO, by the state of activation of the
      macrophage, and by the cytokines involved in the immune response.

PMID- 7513600
TI  - Management of advanced rectal cancer.
AB  - If possible, palliative resection should be undertaken for advanced rectal cancer
      as it provides good relief of local symptoms; there is, however, little evidence
      that it prolongs survival. If palliative excision is not possible, endoscopic
      transanal resection may be used for obstructing lesions at or below the
      peritoneal reflection. Laser therapy is an alternative in the frail. Both
      procedures allow quick and effective relief of symptoms. These methods and other
      options for treating advanced rectal cancer are described in this review.

PMID- 7513599
TI  - The new atypical antipsychotics. A lack of extrapyramidal side-effects and new
      routes in schizophrenia research.

PMID- 7513597
TI  - Processing of defined T-cell epitopes after phagocytosis of intact bacteria by
      macrophages.

PMID- 7513601
TI  - Protein induced by vitamin K absence or antagonist II as a prognostic marker in
      hepatocellular carcinoma. Comparison with alpha-fetoprotein.
AB  - BACKGROUND: Protein induced by vitamin K absence or antagonist II (PIVKA-II) was
      widely used as a diagnostic marker for hepatocellular carcinoma (HCC), however,
      its prognostic value is unclear. The authors evaluated PIVKA-II
      clinicopathologically as a prognostic marker for HCC. METHODS: The relationship
      between pathologic prognostic factors and plasma PIVKA-II and alpha-fetoprotein
      (AFP) was investigated in 72 patients with resectable HCC measuring less than 6
      cm in greatest dimension. RESULTS: PIVKA-II shows significantly lower
      sensitivity, but higher specificity than AFP, and the use of these two
      complementary markers appears to be useful in the diagnosis of HCC. The
      frequencies of intrahepatic metastasis, portal vein tumor thrombus, hepatic vein
      tumor thrombus, and capsular infiltration were significantly higher in patients
      with positive PIVKA-II than in those with negative-PIVKA-II, and the recurrence
      free rate was significantly lower in patients with positive rather than with
      negative PIVKA-II. However, there were no significant differences between the
      patients who were AFP positive and those who were AFP negative in pathologic
      prognostic factors and the recurrence-free rate. From univariate and multivariate
      analyses, the authors find that PIVKA-II is one of the risk factors for
      recurrence of HCC after hepatectomy. CONCLUSIONS: PIVKA-II may be a useful marker
      for the prediction of intrahepatic spread and for the prognosis of HCC. In
      addition, PIVKA-II-positive patients, thus, need aggressive postoperative
      adjuvant therapy for undetectable residual tumors and careful postoperative
      monitoring to enable the early recognition of recurrence.

PMID- 7513603
TI  - Serum tumor marker decline is an early predictor of treatment outcome in germ
      cell tumor patients treated with cisplatin and ifosfamide salvage chemotherapy.
AB  - BACKGROUND: Serum tumor marker regression (alpha-fetoprotein [AFP] and human
      chorionic gonadotrophin [hCG]) was studied in patients treated with ifosfamide
      based chemotherapy for cisplatin-resistant germ cell tumors (GCT) to investigate
      the role of marker regression as a predictor of treatment outcome. METHODS: Fifty
      four patients treated with cisplatin and ifosfamide-containing therapy were the
      subject of this retrospective analysis. The serum tumor marker half-life (T1/2)
      for the first two cycles of therapy was calculated for each patient using all
      marker values Day 7 through the end of the second treatment cycle. A calculated
      T1/2 for hCG of less than or equal to 3 days or a calculated T1/2 for AFP of less
      than or equal to 7 days was defined as appropriate marker regression; any T1/2
      greater than these values was considered prolonged. A variable designated "marker
      decline" was defined to indicate whether the serum tumor marker half-life of AFP
      and/or hCG was satisfactory or unsatisfactory for each individual patient. Both
      univariate and multivariate analyses were conducted to investigate "marker
      decline" as a predictor for response, event-free survival (time to death or
      relapse), and overall survival. RESULTS: Satisfactory marker decline predicted an
      improved event-free survival and overall survival. The median event-free survival
      for patients with an unsatisfactory marker decline was 5.8 months versus 20.7
      months for patients with a satisfactory marker decline. Survival for patients
      with an unsatisfactory marker decline was 6.3 months versus 20.7 months for those
      patients with a satisfactory marker decline. Further evaluation demonstrated that
      hCG decline was a stronger predictor for improved survival than AFP decline. A
      multivariate analysis performed on selected clinical variables using a Cox
      regression model demonstrated that marker decline, pretreatment hCG, and primary
      site were independent predictors for event-free and overall survival.
      CONCLUSIONS: The rate of serum AFP and/or hCG decline during the first two cycles
      of therapy was predictive for event-free and overall survival in GCT patients
      treated with ifosfamide-based salvage therapy. Those patients with an appropriate
      serum tumor marker decline had a longer event-free and overall survival. When
      evaluated separately, the rate of hCG decline was more predictive of treatment
      outcome than decline of AFP. The rate of serum tumor marker regression during the
      first two cycles of therapy is a clinically useful tool in assessing treatment
      outcome at an early point in therapy and may thereby identify patients who could
      benefit from a change to more intensive therapy.

PMID- 7513605
TI  - Reduction of tumor necrosis factor production by splenocytes from v-Ha-ras
      oncogene-bearing mice.
AB  - Mice containing the activated v-Ha-ras oncogene driven by the mouse mammary tumor
      virus promoter/enhancer produced less tumor necrosis factor (TNF) than
      genetically identical animals without it. Inbred Oncomice containing the v-Ha-ras
      oncogene and inbred FVB mice without it were grown for 6 months. Splenocytes were
      isolated and stimulated in vitro to produce tumor necrosis factor (TNF) and gamma
      interferon (IFN). TNF production by cells from Oncomice was significantly
      decreased compared to cells from FBV mice. There was a tendency for decrease, but
      no significant difference was seen on IFN release. These observations suggest
      that the oncogene may play a role in the immune system.

PMID- 7513604
TI  - Clinical and biologic characteristics of CD7+ acute myeloid leukemia. Our
      experience and literature review.
AB  - Six patients with acute myeloid leukemia (AML) expressing CD7 antigen (CD7+ AML)
      were studied. They consisted of five patients with M1 and one with an M2
      morphology. Two cases expressed other lymphoid-associated antigens, in addition
      to CD7. The complete remission rate was 50%. One patient had central nervous
      system recurrence. Cytogenetic analysis demonstrated normal karyotypes in all the
      cases. All but one had germline configurations of the T-cell receptor (TCR) genes
      and immunoglobulin heavy chain gene. However, all did not have detectable
      recombinase activating gene-1 activity by the RT-PCR technique. We performed
      colony formation assay in two patients, and no enhancement of colony formation by
      granulocyte colony-stimulating factor was noted. The results presented here,
      together with those reported previously, suggest that CD7+ AML may demonstrate
      lineage infidelity.

PMID- 7513606
TI  - Association between bleomycin genotoxicity and non-constitutional risk factors
      for head and neck cancer.
AB  - Sensitivity of phytohaemagglutinin-stimulated lymphocytes to bleomycin
      clastogenicity is increased in patients with tumours in organs and tissues that
      are in direct contact with the external environment, such as the mucosa of the
      head and neck. Sensitivity to bleomycin may reflect a genetically determined
      hypersensitivity to certain genotoxicants and therefore may be important in the
      carcinogenic process. In this study the applicability of bleomycin genotoxicity
      was investigated in cultured lymphocytes of forty individuals without a tumour
      history. No correlations were observed with increasing age or the well-known head
      and neck cancer risk factors alcohol and tobacco consumption. Since inter
      individual variation in sensitivity greatly exceeded intra-individual variation,
      our results suggest that an elevated bleomycin clastogenicity score may identify
      individuals who have a constitutional hypersensitivity towards certain
      genotoxicants and may show an increased cancer susceptibility.

PMID- 7513607
TI  - Effects of signalling transduction modulators on the transformed phenotypes in v
      H-ras-transformed NIH 3T3 cells.
AB  - Several signalling transduction modulators were used to examine their effects on
      the morphological changes, foci formation in soft agar and cellular growth in v-H
      ras-transformed NIH 3T3 cells. The results from this study showed that specific
      tyrosine kinase inhibitors (genistein and tyrphostin 23) and cyclic AMP-elevating
      agents (forskolin and 3-isobutyl-1-methyl-xanthine) could effectively induce
      differential flat phenotype of v-H-ras transformant at micromolar concentrations.
      At the same dose range, both signalling modulators also caused a significant
      suppression of anchorage-independent and cellular growth in the same
      transformant. By contrast, compound inhibitors such as protein kinase C
      (staurosporin and H-7), phospholipase A2 (aristolochic acid), phospholipase C
      (neomycin sulfate) and cyclooxygenase (indomethacin) all did not alter the
      cellular morphology or foci formation in soft agar, although PKC inhibitors
      exhibited a slight inhibition on the cellular growth. Based on these
      observations, we propose that the alterations of protein kinase A or tyrosine
      kinase-associated signal pathways is necessary and the original cause of the
      transformation event, but that increase of the activities of protein kinase C,
      phospholipase C, phospholipase A2 or cyclooxygenase probably is an indirect
      result of the v-H-ras-mediated transformation.

PMID- 7513608
TI  - Homozygous deletions within chromosomal bands 9p21-22 in bladder cancer.
AB  - The loss of DNA sequences on chromosomal bands 9p21-22 has been documented in a
      variety of malignancies including leukemias, gliomas, lung cancers, and
      melanomas. Because of the high incidence of monosomy 9 detected by both
      cytogenetics and loss of heterozygosity studies in bladder cancer, we examined
      seven bladder cancer cell lines for deletions in this region. Using seven DNA
      probes that span the region of 9p21-22 as well as a functional assay for
      methylthioadenosine phosphorylase (MTAP), which maps to 9p21, we found four cell
      lines that had small homozygous deletions. These deletions map centromeric to the
      interferon (IFN) gene cluster and telomeric to D9S171. Only one of the cell lines
      with deletions had a cytogenetically evident lesion in this chromosomal region.
      Preliminary loss of heterozygosity studies with 10 primary bladder cancer
      specimens using 10 markers spanning chromosome 9 revealed loss of heterozygosity
      at the IFN locus with retention of heterozygosity with more centromeric 9p
      markers and all informative 9q markers in the tumor of one patient. These data
      suggest that loss of a tumor suppressor gene on 9p21-22, which may represent a
      general pathway of oncogenesis, is important in bladder cancer development.

PMID- 7513602
TI  - Benign and malignant salivary gland-type mixed tumors of the lung.
      Clinicopathologic and immunohistochemical study of eight cases.
AB  - BACKGROUND: Primary lung tumors showing features of salivary gland-type neoplasms
      are extremely rare. METHODS: Eight patients with primary lung neoplasms showing
      light microscopic and immunohistochemical features of salivary gland-type mixed
      tumors were studied. RESULTS: The patients were six women and two men, ages 35-69
      years (mean, 52.5 years). The tumors ranged from 2 to 16 cm in greatest diameter.
      In two patients the lesions presented as polypoid endobronchial lesions
      obstructing the lumen; in another two patients the lesions were found in close
      proximity or in continuity with a bronchus; in three patients, the lesions
      presented as peripheral parenchymatous nodules unrelated to a bronchus; and in
      one patient, the relationship to the bronchus could not be determined.
      Histologically, the lesions were biphasic, showing admixtures in varying
      proportions of epithelial elements containing a predominant myoepithelial cell
      population with a stromal component containing an abundant myxoid or focally
      chondroid matrix. Immunohistochemical studies showed strong positivity of the
      cells in the epithelial component with low molecular weight keratins (CAM 5.2),
      and to a lesser extent with broad spectrum keratin, actin, and vimentin
      antibodies. The cells also showed variable reactivity in the epithelial and
      nonepithelial elements with S-100 protein and glial fibrillary acidic protein.
      Six tumors were grossly and histologically benign; in two patients, the tumors
      were larger, locally invasive, and showed more atypical histologic features. All
      patients were treated with surgical excision. On follow-up, of the six patients
      with histologically benign-appearing tumors, one was alive and well 6 years after
      surgery; another died 4 years after surgery of a second unrelated malignancy; one
      died during the immediate postoperative period of myocardial infarction; and
      three have been lost to follow-up. In the two patients with histologically
      atypical lesions, the tumors recurred and metastasized after 2 and 3 years,
      respectively, with one of them leading to death caused by widespread metastases
      and superior vena cava syndrome. CONCLUSIONS: Review of the literature and the
      findings in the current series indicate that salivary gland-type mixed tumors of
      the lung may present with a spectrum of histologic features and clinical
      behavior, ranging from benign to frankly malignant, similar to that observed for
      their salivary gland counterparts. Size of the lesion at the time of
      presentation, extent of local infiltration, and degree of mitotic activity appear
      to be the most reliable prognostic features of these tumors.

PMID- 7513609
TI  - AGM-1470, a potent angiogenesis inhibitor, prevents the entry of normal but not
      transformed endothelial cells into the G1 phase of the cell cycle.
AB  - AGM-1470 is a potent angiogenesis inhibitor that is very effective in inhibiting
      endothelial cell proliferation in both in vitro and in vivo models and that
      prevents tumor growth in vivo. Although this molecule appears to be a most
      promising anticancer drug, its mechanism of action has not yet been elucidated.
      In this study, we examined the effects of AGM-1470 on the cell cycle of normal
      and transformed endothelial cells. We showed that AGM-1470, at picomolar
      concentrations, specifically inhibits the proliferation of both bovine aortic
      endothelial cells and human umbilical vein endothelial cells. AGM-1470 was
      ineffective in significantly inhibiting the proliferation of Ea.hy926 cells, a
      hybrid cell line obtained by the fusion of human umbilical vein endothelial cells
      with a human carcinoma cell line, or cEnd.1 cells, a polyoma middle T oncogene
      transformed endothelioma cell line derived from mouse embryo. Using a double
      labeling technique with anti-Ki67 antibodies and propidium iodide, we
      demonstrated, with flow cytometry analysis, that AGM-1470 specifically prevents
      the entry of endothelial cells into the G1 phase of the cell cycle. We also
      showed that AGM-1470 was ineffective in inhibiting endothelial cell migration
      toward laminin or capillary-like tube formation inside a type I collagen matrix
      induced by phorbol esters. Our data strongly suggest that AGM-1470 is a molecule
      that specifically inhibits a cell cycle control pathway active in normal cells
      but which could be bypassed or altered in transformed cells.

PMID- 7513611
TI  - Altered queuine modification of transfer RNA involved in the differentiation of
      human K562 erythroleukemia cells in the presence of distinct differentiation
      inducers.
AB  - Altered queuine modification of tRNA has been correlated to neoplasia and cell
      differentiation, but much of the existing evidence is only circumstantial. In the
      present study, we used several distinct differentiation inducers to measure
      changes in Q-family tRNA species during the erythroid differentiation of human
      K562 erythroleukemia cells. Treatment of K562 cells with 3.6 microM 1-beta-D
      arabinofuranosylcytosine (ara-C), 1 mM sodium butyrate, 0.1 mM hemin, or 5 microM
      5-azacytidine resulted in growth inhibition, erythroid differentiation, and
      changes in queuine content of tRNA. In the presence of the irreversible inducer
      ara-C, the queuine content of tRNA increased markedly when the cells
      differentiated into benzidine-positive erythroid cells, and cell growth was
      inhibited. The increase in the queuine content of tRNA in differentiated K562
      cells was an irreversible event. In cells incubated with the reversible inducer
      sodium butyrate, an increase in the queuine content of tRNA was correlated with
      the increase in benzidine-positive erythroid cells throughout the culturing
      period. After removal of the drug at 48 h, the queuine content of tRNA decreased
      concomitant with a decrease in benzidine-positive cells. Treatment with another
      reversible inducer, hemin, caused only a transient increase in the queuine
      content of tRNA, which was not correlated with the steady increase in benzidine
      positive erythroid cells. The agent 5-azacytidine slightly inhibited cell growth
      but did not significantly change the percentage of benzidine-positive cells and
      the queuine content of tRNA. We further clarified the changes in queuine content
      of tRNA by analyzing the Q-containing isoacceptors of Q-family tRNA species
      including tRNA(Tyr), tRNA(His), tRNA(Asp), and tRNA(Asn) by RPC-5 chromatography,
      and found that the change in queuine content of tRNA(Tyr) was greater than the
      other Q-family tRNA species during induction by ara-C, sodium butyrate, and
      hemin. Our results indicate that the change in queuine content of tRNA is an
      irreversible event of terminal differentiation in ara-C induction and is a
      transient event of reversible differentiation in hemin induction. Sodium butyrate
      induction might represent a status between irreversible and reversible
      differentiation. Q-containing isoacceptors of tRNA might potentially play an
      important biological role during K562 cell differentiation.

PMID- 7513610
TI  - A monoclonal antibody inhibits adhesion to fibronectin and vitronectin of a colon
      carcinoma cell line and recognizes the integrins alpha v beta 3, alpha v beta 5,
      and alpha v beta 6.
AB  - Using whole viable human colon carcinoma HT29 cells as immunogen, we produced a
      monoclonal antibody (mAb) termed 69-6-5. The antibody was functionally selected
      on its anti-cell-spreading activity. By immunoprecipitation of surface
      radiolabeled cell lysates from HT29-D4 cells (an HT29 cell clone), mAb 69-6-5
      recognized a molecular complex resembling integrin heterodimers. Sequential
      immunodepletions with mAb to the integrin alpha v subunit demonstrated that this
      complex was composed of alpha v-containing integrins. Accordingly, mAb 69-6-5
      reacted with integrin alpha v beta 3 immunopurified from melanoma cells and
      integrins alpha v beta 5 and alpha v beta 6 immunopurified from pancreatic
      carcinoma cells. In cell adhesion assays, the 69-6-5 mAb was able to inhibit
      strongly in a dose-dependent manner arginine-glycine-aspartic acid-mediated
      adhesion of HT29-D4 cells to vitronectin, fibronectin, or ProNectin F but not to
      laminin or collagen. Immunoprecipitations with beta chain-specific antisera
      indicated that these cells express integrins alpha v beta 5 (receptor for
      vitronectin) and alpha v beta 6 (receptor for fibronectin) but neither alpha v
      beta 1 nor alpha v beta 3. In summary, these results indicated that mAb 69-6-5
      reacts with several alpha v integrins and that it can effectively interfere with
      the adhesive functions of at least alpha v beta 5 and alpha v beta 6, which
      represent the major receptors on HT29-D4 cells responsible for their adhesion on
      vitronectin and fibronectin.

PMID- 7513612
TI  - Activation of a tumor-associated protein kinase (p40TAK) and casein kinase 2 in
      human squamous cell carcinomas and adenocarcinomas of the lung.
AB  - Several non-small cell lung carcinomas (squamous cell carcinomas and
      adenocarcinomas) were analyzed for protein kinase activity. Soluble protein
      extracts derived from these tumors and from the lung parenchyma adjacent to the
      tumors were resolved by Mono Q anion exchange chromatography, and the fractions
      were assayed for phosphotransferase activity towards in vitro substrates. Myelin
      basic protein, casein, and a ribosomal S6-1 COOH-terminus peptide were efficient
      substrates for protein kinases that exhibited elevated phosphotransferase
      activity in the tumor extracts when compared to extracts derived from the
      adjacent nonneoplastic lung or from the lung parenchyma from patients with
      nonneoplastic lung disorders. Casein phosphotransferase activity was resolved
      into two peaks that eluted at 0.44 M NaCl and 0.56 M NaCl. The second peak was
      identified as casein kinase 2, based upon immunoreactivity to casein kinase 2
      specific antipeptide antibodies and its sensitivity to inhibition by heparin
      sulfate. Myelin basic protein phosphotransferase activity eluted at 0.44 M NaCl,
      but Western blot analysis revealed that this could not be ascribed to mitogen
      activated protein (MAP) kinases. This tumor associated protein kinase, designated
      p40TAK, exhibited a molecular mass of approximately 40 kDa upon gel filtration.
      In addition to myelin basic protein, it phosphorylated S6 peptide analogues and
      histone H1 on seryl residues. Like casein kinase 2, p40TAK exhibited elevated
      basal phosphotransferase activity in squamous cell carcinomas and adenocarcinomas
      of the lung when compared to the nonneoplastic lung parenchyma adjacent to the
      tumor.

PMID- 7513613
TI  - Role of selectins, a new family of adhesion molecules, in ischaemia-reperfusion
      injury.

PMID- 7513615
TI  - Immunization with thyroglobulin-specific cytotoxic T cell hybridoma induces anti
      thyroglobulin antibodies: characteristics of monoclonal anti-thyroglobulin auto
      antibody.
AB  - We have produced five monoclonal autoantibodies (mA-Abs) to thyroglobulin (Tg)
      and more precisely to one epitope located within the < 10-kDa pTg tryptic
      fragment suspension capable of inducing experimental autoimmune thyroiditis
      (EAT). They were selected from spleen cells from CBA/J mouse immunized with the
      syngeneic cytotoxic T cell hybridoma HTC2. HTC2 cells are specific for one Tg
      epitope located within the EAT inducer pTg tryptic fragments and are able to
      prevent EAT induction by pTg. The restricted specificity of the humoral response
      previously observed in vivo was further demonstrated and defined in vitro at the
      single cell level. Competitive studies for binding to pTg or to the < 10-kDa pTg
      tryptic fragments demonstrated that HTC2-induced anti-Tg mA-Abs recognized an
      epitope(s) located in the < 10-kDa pTg tryptic fragment (as did 3B8G9, one
      conventional anti-Tg mA-Ab we selected). We ruled out the possibility that HTC2
      induced anti-Tg A-Abs belong to the group of the natural A-Abs due to the lack of
      recognition of actin, dsDNA, TNP-ovalbumin, tubulin, their isotypes (IgG1 or
      Ig2a), and their affinities (in the 10(-7) M order of magnitude). The results
      strengthen the hypothesis that T and B cells sharing the same specificity can
      express similar idiotopes on their respective receptors for antigen. They also
      demonstrate the existence of a regulatory idiotypic network that could explain
      the protection from EAT after injection of inactivated HTC2 cells or its anti
      clonotypic mAb.

PMID- 7513614
TI  - Nitric oxide and cardiovascular disease.

PMID- 7513618
TI  - [Phospholipid components in BALFS from bleomycin induced pulmonary fibrosis in
      rats].
AB  - Qualitative and quantitative analysis was performed on 5 components of
      phospholipids (PL) isolated from bronchoalveolar lavage fluid (BALF) during the
      development of bleomycin induced pulmonary fibrosis in rats with high-performance
      liquid chromatography (HPLC). The measurement of cells and protein in BALF, the
      pathologic and morphometric observation with light and electronic microscope were
      also done. Results indicated that the changes both in BALF cells and in lung
      histopathology were similar, the amount of protein in BALF increased, the total
      amount of PL in BALF increased more than 1.8-fold over control animals at days 28
      after administration of Bleomycin, phosphatidylglycerol (PG) decreased with time,
      phosphatidylinositol (PI) and phosphatidylethanolamine (PE) increased, PG/PI
      ratio decreased, the PG/PI ratio could be used as a marker for pulmonary
      fibrosis.

PMID- 7513616
TI  - Development of reactivity to new myelin antigens during chronic relapsing
      autoimmune demyelination.
AB  - Cells from 25 mice at different stages of experimental autoimmune
      encephalomyelitis (EAE) adoptively transferred using lymph node cells sensitized
      to a synthetic encephalitogenic peptide of myelin basic protein (p87-99) were
      examined for reactivity to a different encephalitogenic myelin antigen,
      proteolipid protein (PLP). Cellular reactivity to a synthetic encephalitogenic
      peptide of PLP (pPLP) was found in 3/5 mice with acute EAE, 4/9 with chronic EAE,
      1/6 mice with EAE in remission, and 0/5 during relapse. No proliferation to pPLP
      was seen in naive mice or in healthy mice immunized with p87-99. Two of 13 mice
      developed typical EAE after the serial transfer of cells from animals with p87-99
      induced EAE had been activated with pPLP in vitro. Controls consisted of
      recipients of (a) pPLP-activated cells from naive donors or donors immunized with
      a nonencephalitogenic MBP peptide, (b) cells from mice immunized with MBP
      activated in vitro with irrelevant antigen, or (c) ovalbumin-activated cells
      serially transferred from mice with adoptively transferred EAE. No control mice
      developed signs. These results suggest that during the course of myelin breakdown
      caused by an immune response to one myelin component (MBP), autoimmune reactivity
      to at least one additional myelin antigen (PLP) can arise. Furthermore, the
      acquired cellular reactivity to additional myelin components may be sufficient in
      some cases to induce disease itself, perhaps lending insight into mechanisms
      involved in disease progression.

PMID- 7513619
TI  - [Histamine release from mast cell induced by main pathogenic bacteria of
      respiratory infections in Guangzhou area].
AB  - The methodology for isolating rat peritoneal mast cell was established. The main
      pathogenic bacterial ultrasonicates of respiratory infection in GuangZhou area
      have been examined for their ability to release histamine from purified rat
      peritoneal mast cells. The results were as following: (1) 7 pathogenic bacteria
      can cause direct release of histamine from rat mast cells. The most effective
      histamine releasers were P. mira (histamine release percent is 26.89% +/- 6.70%),
      Strep. Pneu (24.16% +/- 3.71%), E. Coli (20.40% +/- 4.83%) and K. Pneu (17.91% +/
      4.60%). (2) Histamine release initiated by bacterial ultrasonicates was
      completed within 30 minutes E. Coli differed from K. Pneu induced histamine
      release was independent of its dose. (3) The products of K. Pneu did not induce
      histamine release directly and bacterial hemolysin may play a potent role in
      bacteria-induced release of histamine. Our findings provide some evidence for
      mechanism by which respiratory bacterial infection can precipitate or exacerbate
      attacks of bronchial asthma.

PMID- 7513617
TI  - Lymphocyte-synovial cell interactions: a role for beta 1 and beta 3 integrin
      mediated adhesion to cellular fibronectin.
AB  - The interactions of lymphocytes with cultured synovial cells derived from
      rheumatoid arthritis patients were examined. A number of lymphoid cell lines
      bound to these cells. The adherence of several of these lines was inhibited by
      antibodies to fibronectin. The adherence of the T cell leukemia Jurkat was
      sensitive to inhibition by antibodies to the fibronectin receptors alpha 4 beta 1
      and alpha 5 beta 1. The adherence of the beta 1 integrin negative B cell line
      RPMI 8866 was inhibited by antibodies to the vitronectin receptor, alpha v beta
      3. The interactions of several other cell lines with synovial cells appeared to
      be independent of this fibronectin-dependent pathway. These results indicate that
      multiple potential adhesion pathways for cellular interactions in the tissues may
      exist. The adherence to cell-associated fibronectin may play a contributory role
      in such processes for certain lymphocyte subsets.

PMID- 7513622
TI  - [Schistosoma japonicum adult worm RNA isolation with Chomczynski's method].
AB  - A rapid method of total RNA of Schistosoma japonicum adult worm isolation by
      single step extraction with an acid guanidinium thiocyanate-phenol-chloroform
      mixture is described. The method provides a pure preparation of intact RNA and
      can be completed within several hours. It is particularly useful for isolation of
      RNA from minute quantity of parasite material. Analysis of agarose gels
      electrophoresis reveals that the RNA preparations show a distinct band
      comigrating with 18S rat brain RNA and without large rRNA species. The large rRNA
      is in vivo nicked. The absence of a band at approximately 26S presumably reflects
      post transcriptional processing of the large rRNA.

PMID- 7513621
TI  - Up-regulation of gamma-glutamylcysteine synthetase activity in melphalan
      resistant human multiple myeloma cells expressing increased glutathione levels.
AB  - Levels of intracellular glutathione (GSH) and the GSH-related enzymes gamma
      glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyltranspeptidase (gamma
      GT) were measured in the melphalan-resistant human multiple myeloma cell line
      8226/LR-5 and were compared to those measured in the drug-sensitive 8226/S and
      doxorubicin-resistant 8226/Dox40 cell lines. Both GSH and gamma-GCS activity, the
      rate-limiting step in the de novo synthesis of GSH, were elevated by a factor of
      approximately 2 in the melphalan-resistant 8226/LR-5 cells relative to the other
      two lines. gamma-GT activity was not elevated significantly in the /LR-5 cells.
      Northern analysis with a probe specific for the large subunit of human liver
      gamma-GCS identified two bands (3.2 and 4.0 kb), both of which were increased by
      a factor of 2-3 in the 8226/LR-5 line. Levels of gamma-GCS mRNA expression were
      comparable in the /S and /Dox40 cell lines. Levels of gamma-GT mRNA were similar
      in the /S and /LR-5 lines but were reduced in the /Dox40 cells. These data
      suggest that the increased GSH levels associated with resistance to melphalan in
      the 8226/LR-5 myeloma cells is attributable to up-regulation of gamma-GCS. This
      observation is consistent with recent demonstrations of up-regulation of gamma
      GCS in melphalan-resistant prostate carcinoma cells and cisplatinum-resistant
      ovarian carcinoma cells, suggesting that increased expression of gamma-GCS may be
      an important mediator of GSH-associated resistance mechanisms.

PMID- 7513620
TI  - V79 Chinese hamster lung cells resistant to the bis-alkylator bizelesin are
      multidrug-resistant.
AB  - Bizelesin (U-77779) is a highly potent bis-alkylating antitumor agent that is
      effective against several tumor systems in vitro and in vivo. V79 cells that were
      125- to 250-fold resistant to bizelesin developed after constant exposure to
      gradually increasing concentrations of the drug. Resistant cells exhibited a
      multidrug-resistant phenotype and genotype as indicated by cross-resistant to
      several structurally and functionally unrelated drugs, e.g., colchicine,
      actinomycin D, and Adriamycin, and overexpression of mdr mRNA. Very low levels of
      cross-resistance to the alkylating agents cisplatin and melphalan were seen.
      Multidrug-resistant mouse leukemia (P388/Adriamycin-resistant) and human
      (KB/vinblastine-resistant) cells were also resistant to bizelesin. Bizelesin
      resistance was unstable and decreased when cells were grown in the absence of the
      drug. Resistant and sensitive cell lines had similar levels of glutathione, and
      bizelesin cytotoxicity for resistant cells was not markedly affected by treatment
      with buthionine sulfoximine. Cross-resistance between bizelesin and several of
      its analogs is reported.

PMID- 7513623
TI  - Evidence that GYKI 52466, a novel non-NMDA antagonist enhances the decay of
      kainate-induced current in cultured chicken cortical neurons.
AB  - The effect of a novel non-competitive non-NMDA glutamate receptor antagonist,
      GYKI 52466 was studied on the glutamate agonist-induced currents in one month old
      cultured embryonal chicken brain neurons by a whole cell patch-clamp technique.
      AMPA, applied in different concentrations (30-1000 microM) did not evoke any
      current. Kainate evoked an increase of steady-state current (KA-current). NMDA
      induced a current with 5-10 times higher peak amplitude than KA, but GYKI 52466
      failed to affect this current. It reduced the amplitude of KA-current in a
      concentration-dependent (1-100 microM) manner, and produced a slow decay of it.
      The IC50 value of GYKI 52466 against 100 microM KA was 20.4 +/- 6.4 microM with a
      Hill coefficient of 1.12. The inhibition of KA-currents was voltage-dependent
      with greater inhibition between -110 to -40 mV than between -30 and +60 mV. In
      order to compare the effect of GYKI 52466 with a well-known competitive non-NMDA
      antagonist, we also studied the effect of the quinoxalinedione CNQX. When GYKI
      52466 and CNQX were applied together there was only a small additive effect. Our
      results with GYKI 52466 on glutamate agonist-induced currents in embryonic
      chicken cortical neurons are similar to those observed in rat hippocampal
      neurons.

PMID- 7513625
TI  - Immunohistochemical localization of tyrosine hydroxylase, substance P,
      neuropeptide-Y and leucine-enkephalin in developing human retinal amacrine cells.
AB  - Prenatal changes in the neurotransmitter/neuromodulator profiles of tyrosine
      hydroxylase (for dopamine), substance P, neuropeptide Y, and leucine-enkephalin
      were studied in developing human retinal amacrine cells by the use of
      immunohistochemical techniques. Tyrosine hydroxylase was localized between 10 and
      12 weeks of gestation, substance P and neuropeptide Y appeared little later
      around 14 weeks, and leucine-enkephalin-like immunoreactivity was observed at 16
      weeks.

PMID- 7513624
TI  - Topographic distribution of efferent fibers originating from homotopic or
      heterotopic transplants: heterotopically transplanted neurons retain some of the
      developmental characteristics corresponding to their site of origin.
AB  - The present study was undertaken to determine whether the topographical
      distribution of cortical efferents is exclusively dependent on environmental cues
      or is also controlled by intrinsic factors. For the purpose, we used a sensitive
      tract-tracing method (Phaseolus vulgaris leucoagglutinin) to compare the pattern
      of efferent fibers of homotopic and heterotopic transplants of embryonic (E16)
      neocortex. Our findings indicate that transplants of embryonic sensorimotor
      cortex placed homotopically in the sensorimotor cortex of newborn rats distribute
      a set of efferent projections not fundamentally different from that of normal
      sensorimotor cortex. The pattern of efferents arising from transplants of
      embryonic occipital cortex heterotopically placed in the sensorimotor cortex of
      newborns is strikingly different. Heterotopically transplanted neurons: (i) only
      rarely contact normal targets of the motor cortex; (ii) systematically project
      towards normal targets of the visual cortex (primary and secondary visual
      cortical areas, dorsal and ventral lateral geniculate nuclei, lateral dorsal and
      lateral posterior thalamic nuclei, anterior pretectal nucleus and superficial and
      intermediate layers of the superior colliculus); (iii) distribute fibers to
      structures normally receiving fibers from both motor and visual cortices (caudate
      putamen, pontine nuclei), either exclusively into the visual cortico-recipient
      zone of the structure or into both visual and motor cortico-recipient zones.
      Taken together, these results seem to indicate that the heterotopically
      transplanted cells have retained certain anatomical characteristics of their
      locus of origin.

PMID- 7513626
TI  - Two-site immunoassay of recombinant hirudin based on two monoclonal antibodies.
AB  - Two monoclonal antibodies (mAbs), 10-2 and 10-5, both directed against
      recombinant hirudin variant 2-Lys47 (rHV2), were selected for their high affinity
      and epitopic specificities to develop a two-site immunoassay of rHV2. The mAb
      concentrations, incubation time, and temperature were optimized. The immunoassay
      has a detection limit for rHV2 of 45 ng/L in plasma and 30 ng/L in urine. The
      reactivity of the mAbs was tested against rHV2 and several forms of this protein
      truncated in the carboxyl terminus. The capture mAb 10-2 was found to be mainly
      directed against rHV2, whereas tracer mAb 10-5 was independent of the carboxyl
      terminal region of the protein. This explains the high specificity of the
      immunoassay for the 65-amino acid form of hirudin.

PMID- 7513627
TI  - 15-Desmethyl FK-506 and 15,31-desmethyl FK-506 from human liver microsomes:
      isolation, identification (by fast atom bombardment mass spectrometry and NMR),
      and evaluation of in vitro immunosuppressive activity.
AB  - 15-Desmethyl FK-506 and 15,31-desmethyl FK-506 metabolites extracted from
      incubated human liver microsomes were separated by normal and reversed-phase
      HPLC. The metabolites were identified by fast atom bombardment/mass spectrometry
      and nuclear magnetic resonance spectroscopy. The in vitro 50% inhibitory
      concentration, tested against bidirectional mixed lymphocyte reactions, was 325
      mg/L for 15,31-desmethyl FK-506 and 4 mg/L for 15-desmethyl FK-506, indicating
      that these products of FK-506 demethylation retain in vitro immunosuppressive
      activity.

PMID- 7513628
TI  - Iron-deficiency anemia is associated with high concentrations of transferrin
      receptor in serum.
AB  - We evaluated the use of transferrin receptor (TfR) in serum as an index of iron
      deficiency in 19 patients diagnosed as having iron-deficiency anemia, in 17
      patients with anemia of chronic disease, and in a control group of 19 nonanemic
      patients who underwent elective ocular or nasopharyngeal surgery. The assessment
      of iron status of the anemic patients was based on the presence of stainable iron
      on bone marrow examination. In the patients with iron-deficiency anemia, the
      serum TfR concentration was 5.3 +/- 1.8 mg/L (mean +/- SD), significantly higher
      than in the control group (1.7 +/- 0.5 mg/L) or in the patients with anemia of
      chronic disease (1.6 +/- 0.4 mg/L). This study suggests that serum TfR
      measurement is a reliable index of iron depletion and potentially of importance
      in the diagnosis of iron-deficiency anemia.

PMID- 7513629
TI  - [Cytotoxicity of lymphokine-activated killer cells in conjunction with
      pingyangmycin to human tongue carcinoma (Tca8113) in vitro and vivo].

PMID- 7513631
TI  - Hepatitis C infection in potential recipients with normal liver biochemistry does
      not preclude renal transplantation.
AB  - The hepatitis C virus (HCV) may be an important cause of chronic liver disease in
      renal transplant recipients. We investigated retrospectively the incidence and
      outcome of HCV infection in long-term renal transplant recipients and patients on
      hemodialysis. Stored, pretransplant sera of transplant recipients with normal
      liver biochemistry at surgery were tested for hepatitis C by a second-generation
      enzyme immunoassay. Hemodialysis patients were tested by a first-generation
      enzyme-linked immunosorbent assay (ELISA) against c100-3. We studied 252 renal
      transplant recipients and 58 hemodialysis patients followed for 65 +/- 10 months
      and 26 +/- 6 months, respectively. Fifteen percent (38/252) of the transplant
      recipients were HCV positive as were 3/58 (5%) of the hemodialysis patients.
      Overt liver disease occurred in 22/252 (8.7%) transplant recipients and none in
      the hemodialysis group. Thirty-six percent (8/22) of transplant recipients with
      overt liver disease were HCV positive. No HCV-positive patients died of liver
      failure. Of six biopsies in the HCV-positive transplant group, two had
      histological evidence of CAH. CAH was seen in six of eight biopsies in the HCV
      negative transplants and two of these latter patients progressed to cirrhosis. No
      hemodialysis patients had clinical or histological evidence of chronic liver
      disease. Two HCV-negative transplant patients died of liver failure, while no
      deaths related to liver disease occurred in hemodialysis patients regardless of
      HCV status. We conclude that hepatitis C may cause chronic hepatitis in renal
      transplant patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513630
TI  - Omentum and basic fibroblast growth factor in healing of chronic gastric
      ulcerations in rats.
AB  - Omentum was shown to exhibit angiogenic activity, but its role in healing of
      chronic gastric ulcers is unknown. This study was designed to compare the effects
      of omentum and basic fibroblast growth factor (bFGF), a potent angiogenic factor,
      on healing of chronic gastric ulcers in rats. Several series of rats with gastric
      ulcers were used: series A with intact omentum (control), series B with omentum
      resected, and series C with omentum placed on the serosal side of the ulcer.
      Series A-C were divided into four groups treated with vehicle (I); indomethacin
      (II), an inhibitor of prostaglandin formation, difluoromethylornithine (DFMO)
      (III); an inhibitor of polyamine biosynthesis or bFGF (IV). Seven days after
      ulcer induction, the animals were anesthetized, the gastric blood flow (GBF) was
      determined by laser Doppler flowmetry (LDF), and the ulcer area was measured by
      planimetry. Biopsy samples of the ulcer margin were taken for determination of
      the number of capillaries and myofibroblasts in the granulation tissue.
      Attachment of omentum significantly accelerated ulcer healing, whereas
      omentectomy delayed this process. LDF revealed the decrease in the GBF at the
      ulcer margin to 45% and at the ulcer bed to 18% of the value recorded in the
      intact adjacent mucosa. Attachment of the omentum significantly increased the
      blood flow at the ulcer margin and increased the number of capillaries and
      myofibroblasts in the granulation tissue. Indomethacin (1 mg/kg/day) that
      inhibited mucosal PGE2 by about 85% delayed significantly ulcer healing without
      affecting the blood flow in the ulcer area.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513632
TI  - Clinical significance of hepatitis C virus (HCV) infection in liver transplant
      recipients. Role of serology and HCV RNA detection.
AB  - Hepatitis C virus (HCV) infection was studied in 60 liver transplant recipients.
      Antibodies to HCV were tested by both a second-generation ELISA test and a four
      recombinant immunoblot assay (4-RIBA) just before the transplant and every three
      months thereafter. HCV RNA detection was performed by polymerase chain reaction
      (PCR) at least three times after the transplant in all the patients. Thirty-nine
      patients tested negative by ELISA before LT (group A), 14 patients tested
      positive by both serological tests (group B), and seven tested positive only by
      ELISA (group C). Posttransplant hepatitis was diagnosed in 11/14 in group B in
      comparison with 3/39 in group A (P < 0.001) and 1/7 in group C (P < 0.05). HCV
      RNA was detected in the sera of 14/14 patients in group B but in only 1/7 in
      group C and 6/39 in group A. Only 2/15 patients developed posttransplant
      hepatitis in the absence of HCV RNA detection. These data suggest that HCV is the
      major cause of hepatitis after LT. Patients HCV seropositive by RIBA test before
      the transplant formed a group of high-risk patients for developing viremia and
      hepatitis afterwards.

PMID- 7513634
TI  - [Immunoprophylactic and immunotherapeutic effects of adoptively transferred LAK
      cells on L615 leukemia suffering mice].
AB  - The immunoprophylactic and immunotherapeutic effects of LAK cells transferred
      adoptively on L615-suffering mice were studied. The results showed that adoptive
      transfer of LAK cells could increase the survival rate of the mice and prolong
      the mean survival time of mice with advanced L615 leukemia. IL-2 in appropriate
      concentration was required in the adoptive immunotherapy, and the combined use of
      LAK cells with 5-FU or IFN-r had no additive immunotherapeutic effects. The
      results also revealed that the immunotherapeutic activity of the transferred LAK
      cells maintained a relatively long period of time in the host body.

PMID- 7513633
TI  - [Establishment and application of transplantable models of human esophageal
      carcinoma in nude mice].
AB  - We have successfully established two human esophageal carcinoma models in nude
      mice by transplantation of surgical specimen from patients with esophageal
      cancer. Histopathological study revealed that one was squamous cell carcinoma
      (HEC2) and the other adeno-squamous cell carcinoma (HEC6). Light and electron
      microscopy showed that their morphology was similar to that of the original
      tumors. The transplanted tumors have been maintained for more than four years
      through more than 50 passages. The tumors grew steadily and fast. The rate of
      successful inoculation was 100%. Bleomycin A5 and 5-Fluorouracil (5-Fu) were used
      for treatment of HEC6. Results showed that Bleomycin A5 exhibited a remarkable
      growth inhibition on the HEC6. The inhibition rates of two separate experiments
      were 56.5% and 87.8% respectively (compared with the control group, P < 0.01).
      The inhibition rates of 5-Fu were 6.5% and 36.6% respectively. Compared with the
      control group, there was no significant difference statistically HEC2 was treated
      by X-ray or X-ray combined with hematoporphyrin derivative (HPD), the tumor
      growth inhibition was 57.7% and 85.4% respectively.

PMID- 7513636
TI  - Mechanisms involved in the antiinflammatory effect of propolis extract.
AB  - Propolis is a natural product produced by the honey bee. The extract contains
      amino acids, flavanoids, terpenes and cinnamic acid derivatives. In various in
      vitro models propolis extract was shown to inhibit platelet aggregation and to
      inhibit eicosanoid synthesis, suggesting that it might have potent
      antiinflammatory properties. A 13% aqueous extract was tested orally in three
      dose levels (1, 5 and 10 ml/kg) on the carrageenan rat paw oedema model and on
      adjuvant-induced arthritis in rats. In both models, the extract showed potent
      dose-related antiinflammatory activity, which compared well with that of
      diclofenac (as a reference standard). The extract was then tested on an isolated
      sensitized guinea pig lung preparation to study its effect on the release of
      prostaglandins, leukotrienes and histamine. It is concluded that propolis extract
      has potent antiinflammatory properties in vivo. Its activity can be well
      correlated with its effects on the release of various mediators of inflammation.

PMID- 7513637
TI  - The cellular basis of olfaction.
AB  - Smell is one of the most important senses driving basic patterns of behaviour in
      most of the earth's animal species. It plays a role in food-finding, kin
      recognition, reproductive behaviour, the predator-prey relationship, mother
      infant recognition, homing behaviour, nest-finding, and other behaviours.
      Students of animal behaviour have studied the role of olfaction extensively, but
      until recently little detail was known about the biology of the cells that
      respond to odours. This article describes some recent advances in our
      understanding of these cells.

PMID- 7513638
TI  - Antibody engineering.
AB  - A century ago, in his private laboratory in Berlin, Paul Ehrlich conceived and
      developed the idea of using antibodies to target toxic molecules. Recent advances
      in genetic engineering have enormously extended the potential of this concept for
      the treatment of malignant diseases, by making it possible to isolate genes
      encoded for the antibody variable regions and to manipulate them to create new
      molecules.

PMID- 7513635
TI  - [Clinicopathologic features of small hepatocellular carcinoma--an analysis of
      ninety-three cases].
AB  - A clinicopathologic analysis of 93 hepatectomies of < 3 cm small hepatocellular
      carcinoma (small-HCC) over the last ten years was made, which accounted for 8.5%
      in 1096 resected HCC during the same period. Serum AFP levels of > or = 400
      micrograms/L in patients with small-HCC accounted for 40.3%. The rate of capsule
      formation was 58.1%, and the incidences of tumor direct invasion, cancer thrombus
      as well as tumor satellites were 33.3%, 28% and 3.2%, respectively. The 5-year
      postoperative survival rate of patients with small-HCC was 77.9%. It is proposed
      that the essential features of < 3 cm small-HCC are: (1) expanding growth pattern
      and capsule formation in majority of the cases; (2) the lesions are limited,
      seldom occurring long-distance (> 2 cm) invasion; (3) the incidence of cancer
      thrombus and satellites are lower; and (4) the majority of < 3 cm small-HCC are
      of diploid DNA content, showing a relatively slow growth. It is considered that <
      3 cm small- HCC basically reflects the pathobiologic features of early HCC, and
      is an important opportunity of achieving radical therapeutic effect after the
      resection.

PMID- 7513640
TI  - Binding of transforming growth factor-beta (TGF-beta) to pregnancy zone protein
      (PZP). Comparison to the TGF-beta-alpha 2-macroglobulin interaction.
AB  - Pregnancy zone protein (PZP) is quantitatively the most important pregnancy
      associated plasma protein and it has strong similarity to alpha 2-macroglobulin.
      Since alpha 2-macroglobulin is a binding protein for transforming growth factors
      beta (TGF-beta), it was of interest to test whether the related protein, PZP,
      also binds to these growth-regulatory proteins. Using affinity-labelling methods,
      we demonstrate that PZP binds both TGF-beta 1 and TGF-beta 2 and that the binding
      characteristics are similar to those of the TGF-beta-alpha 2-macroglobulin
      interaction. TGF-beta 2 and TGF-beta 1 bind to PZP in a predominantly noncovalent
      manner in vitro. TGF-beta 1 and TGF-beta 2 bind to both the dimeric and
      tetrameric forms of PZP. Our studies also indicate that PZP binds TGF-beta 2 with
      higher affinity than TGF-beta 1. Finally, we demonstrate that PZP inhibits the
      binding of TGF-beta 1 and TGF-beta 2 to their cell surface receptors. The
      increased level of PZP during pregnancy may affect the action of TGF-beta by
      regulating the distribution, clearance and/or general availability of TGF-beta.
      The preferential binding of TGF-beta 2 over TGF-beta 1 by PZP implies that PZP
      may differentially regulate the action of TGF-beta 1 and TGF-beta 2.

PMID- 7513639
TI  - Mechanisms of action of currently prescribed and newly developed antiepileptic
      drugs.
AB  - Clinically available antiepileptic drugs (AEDs) decrease membrane excitability by
      interacting with neurotransmitter receptors or ion channels. AEDs developed
      before 1980 appear to act on sodium (Na) channels, gamma-aminobutyric acid A
      (GABAA) receptors, or calcium (Ca) channels. Benzodiazepines and barbiturates
      enhance GABAA-receptor-mediated inhibition. Phenytoin, carbamazepine and,
      possibly, valproate (VPA) decrease high-frequency repetitive firing of action
      potentials by enhancing Na channel inactivation. Ethosuximide and VPA reduce a
      low threshold (T-type) Ca-channel current. The mechanisms of action of recently
      developed AEDs are less clear. Lamotrigine may decrease sustained high-frequency
      repetitive firing of voltage-dependent Na action potentials, and gabapentin (GBP)
      appears to bind to a specific binding site in the CNS with a restricted regional
      distribution. However, the identity of the binding site and the mechanism of
      action of GBP remain uncertain. The antiepileptic effect of felbamate may involve
      interaction at the strychnine-insensitive glycine site of the N-methyl-D
      aspartate receptor, but the mechanism of action is not yet proven.

PMID- 7513641
TI  - Molecular cloning and characterisation of a neutrophil chemotactic protein from
      porcine platelets.
AB  - In our search for novel chemoattractant factors, we have purified a heparin
      binding protein from porcine platelets which is a potent chemoattractant for
      human neutrophils. The protein has 80 amino acids and a molecular mass of
      8597.5Da as measured by electrospray mass spectrometry. It has been characterised
      by amino acid sequencing and shown to have highest identity to members of the
      human platelet basic-protein-family. Its N-terminal sequence is intermediate in
      length between the human connective-tissue-activating polypeptide III (CTAP-III)
      and neutrophil-activating polypeptide-2 (NAP-2). The porcine NAP-2/CTAP-III shows
      the classic CXC cysteine spacing found towards the N-terminus in the chemokine
      alpha family and contains the ELR motif which has been shown to be essential for
      neutrophil chemotaxis. We have isolated mRNA from porcine platelets and
      constructed a cDNA library containing 1.0 x 10(6) independent clones. Using
      probes based on the protein sequence we have isolated a full length-clone for
      this gene, with an open reading frame containing 119 amino acids. Despite overall
      similarity between the human and porcine proteins, the N-terminal region is
      almost completely different between the two species, with only two identical
      amino acids. The proteolytic cleavage sites required for processing of human
      platelet basic protein are completely missing in the porcine homologue, implying
      a different processing pathway or mechanism. The porcine protein is capable of
      agonizing certain effects of both NAP-2 and CTAP-III when incubated with human
      cells indicating that the same porcine protein may be involved in both processes.

PMID- 7513642
TI  - Polymorphonuclear neutrophils release 35S-labelled proteoglycans into cartilage
      during frustrated phagocytosis.
AB  - Rabbit peritoneal polymorphonuclear neutrophils (PMN), incubated in medium
      containing [35S]sulphate, incorporated 35S into proteoglycan and protein
      fractions. Approximately 46% of the 35S-labelled macromolecules associated with
      the PMN cells after 1 h of incubation were recovered in a cytoplasmic granule
      extract, the majority being present in azurophil granules. Analysis of the
      azurophil granule fraction showed that approximately 90% of the 35S-labelled
      macromolecules were proteoglycans. When challenged with heat-aggregated rabbit
      gamma-globulin in the presence of cytochalasin B and cGMP, PMN were induced to
      release granular enzymes but did not release 35S-labelled proteoglycans into the
      incubation medium. When incubated with articular cartilage slices, PMN released
      their granule 35S-labelled proteoglycan into the medium and into the cartilage
      matrix. Granule enzymes and 35S-labelled granule proteoglycan were extracted from
      the cartilage tissue after incubation and 35S-labelled macromolecules were
      detected in the cartilage tissue by autoradiography.

PMID- 7513644
TI  - Protein kinase C modulates receptor-independent activation of endothelial nitric
      oxide synthase.
AB  - The intracellular regulation of nitric oxide synthase has been the focus of
      intense investigation. Bioassay studies using vascular rings have suggested that
      protein kinase C inhibits endothelium-dependent vascular relaxation. However,
      information regarding the effects of protein kinase C on the synthesis of nitric
      oxide in endothelial cells is not available. Therefore, we investigated the
      effects of protein kinase C to regulate receptor-independent activation of nitric
      oxide synthase activity in cultured bovine pulmonary artery endothelial cells.
      Activation of protein kinase C by phorbol 12-myristate 13-acetate or 1,2
      dioctanoyl-sn-glycerol inhibited receptor-dependent and receptor-independent
      nitric oxide synthase activity. The inhibition of nitric oxide synthase by
      protein kinase C was concentration dependent and markedly blunted by
      staurosporine. The inhibition of protein kinase C by staurosporine alone enhanced
      basal nitric oxide synthase activity. Furthermore, depletion of protein kinase C
      enhanced both basal and agonist-stimulated nitric oxide synthase activity. These
      studies indicate that protein kinase C modulates the activity of the constitutive
      Ca2+/calmodulin-dependent endothelial nitric oxide synthase in the basal state
      and following agonist stimulation through direct inhibition of the enzyme as well
      as receptor desensitization. These direct regulatory effects of protein kinase C
      on endothelial nitric oxide synthase activity may have important implications in
      the physiologic regulation of vascular tone.

PMID- 7513643
TI  - Chondroitin sulphate covalently cross-links the three polypeptide chains of inter
      alpha-trypsin inhibitor.
AB  - Inter-alpha-trypsin inhibitor (ITI) is a tight complex of three different
      proteins: bikunin and two heavy chains H1 and H2. In order to demonstrate that
      the three chains are covalently linked by a chondroitin sulphate chain as
      previously proposed [Enghild, J. J., Salvesen, G., Hefta, S. A., Thogersen, I.
      B., Rutherford, S. and Pizzo, S. V. (1991) J. Biol. Chem. 266, 747-751], ITI was
      extensively digested with thermolysin and the glycosaminoglycan-containing
      fragment was isolated from the digest by ion-exchange chromatography. Its peptide
      structural determination and mass spectrometry analysis both provide evidence
      that the different peptide chains constituting ITI are associated by the new
      cross-link described as the protein-glycosaminoglycan-protein cross-link.

PMID- 7513645
TI  - Involvement of nitric oxide and cyclic GMP in rabbit urethral relaxation.
AB  - Soluble and particulate fractions from rabbit urethra converted [14C]arginine to
      [14C]citrulline, indicating the presence of nitric oxide synthase activity in
      these fractions. Both soluble and particulate nitric oxide synthase activities
      were NADPH dependent, and the soluble activity was Ca2+ dependent. Three nitric
      oxide synthase (NOS) inhibitors affected transmural nerve stimulation induced
      relaxation responses in the rabbit urethra and the activity of soluble nitric
      oxide synthase with the same rank order of potency, i.e., NG-nitro-L-arginine
      (NNA) > NG-methyl-L-arginine (NMA) > canavanine (CAN). The rank order of potency
      with respect to particulate NOS activity was CAN > NMA = NNA. The relaxation
      responses to electrical stimulation were accompanied by increases in cyclic GMP.
      These results suggest that NOS activity found in the soluble fraction of urethral
      homogenates produces nitric oxide that in turn increases cyclic GMP levels which
      mediates the relaxation responses induced by transmural nerve stimulation in the
      rabbit urethra.

PMID- 7513646
TI  - Cell-collagen adhesion is inhibited by monoclonal antibody 33.4 against the rat
      alpha 1-integrin subunit.
AB  - A monoclonal antibody (mAb 33.4) is described which inhibits the adhesion and
      spreading of an adherent cell line (A-cells), established from Morris hepatoma
      7777 and isolated hepatocytes on collagen IV but not on laminin, fibronectin, and
      vitronectin. mAb 33.4 retains its immunological activity after immobilization and
      covalent cross-linking to Protein G-Sepharose and is therefore a suitable tool
      for the preparative equimolar purification of two proteins with M(r) of 130 and
      190 kDa from detergent-solubilized membrane fractions by immunoaffinity
      chromatography. The 190-kDa protein was identified as rat alpha 1-integrin
      subunit by N-terminal amino acid sequencing, while the 130-kDa protein was
      specifically stained by a beta 1-integrin subunit-specific antiserum. In
      immunoblot analysis mAb 33.4 recognized the 190-kDa band, suggesting that it is
      specific for the rat alpha 1-integrin subunit. The epitope recognized by mAb 33.4
      is conformation-dependent because the staining in immunoblots was very strong if
      the SDS-PAGE was performed in the absence of reducing agents. The expression of
      alpha 1 beta 1-integrin in sinusoidal hepatocyte membrane domains of liver
      sections is shown by mAb 33.4 and antisera raised against the rat alpha 1- and
      beta 1-integrin subunits.

PMID- 7513647
TI  - Effects of exogenous FGFs on growth, differentiation, and survival of chick
      neural retina cells.
AB  - Fibroblast growth factors (FGFs) are known to play important roles in various
      processes including development and differentiation. Chick embryo neural retina
      cells, capable of transdifferentiation into lentoid bodies and pigmented cells,
      were used in vitro to examine the effects of exogenous acidic (aFGF) and basic
      FGF (bFGF) on proliferation and protein accumulation. We demonstrate that both
      factors increase the proliferation of glial cells and modulate the survival of
      neurons without affecting protein accumulation within these cells. Moreover, FGFs
      stimulate the differentiation of the photoreceptors. The rate of proliferation
      varies over the period of culture, with a maximum occurring after 2 weeks,
      followed by a decrease concommitant with the appearance of lentoid bodies. The
      concentration of aFGF was measured using an enzyme immuno assay and showed an
      accumulation of this protein only in bFGF-treated cultures, suggesting that bFGF
      positively modulates aFGF synthesis in neural retina cell cultures.

PMID- 7513650
TI  - Immunocytochemical localization of CD44 in the mouse retina.
AB  - The transmembrane glycoprotein CD44 is a cell adhesion molecule which has
      recently been localized in a variety of cell types. It mediates cell attachment
      to extracellular matrix components and also binds to the actin cytoskeleton
      within the cell. In this study, the presence and distribution of CD44 in the
      mouse retina was investigated in order to determine whether this molecule might
      be important for retinal cell adhesion. With immunoperoxidase techniques,
      positive labeling for CD44 was found at the level of the outer limiting membrane
      and in the region just sclerad to it. However, from these light microscope
      results it was not clear if the label was in the photoreceptor inner segments,
      the Muller cell apical microvilli, or both. In order to answer this question,
      cryoultramicrotomy and immunogold labeling were used to demonstrate that CD44 is
      specifically localized to the Muller cell microvilli which appose the
      interphotoreceptor matrix. Western blotting of a retina homogenate showed that
      the anti-CD44 antibody is specific for a protein of approximately 90 kDa which is
      the correct molecular weight for the most abundant form of CD44. These results,
      along with the known binding characteristics of CD44 for the extracellular
      matrix, suggest that CD44 could play a role in mediating the attachment of the
      neural retina to components of the interphotoreceptor matrix.

PMID- 7513648
TI  - Chloride currents in freshly isolated rat retinal pigment epithelial cells.
AB  - Cells of the retinal pigment epithelium (RPE) were isolated from neonatal rats.
      The perforated-patch clamp technique, using amphotericin-B, revealed a chloride
      current, which was detected as a 4,4'-diisothiocyanostilbene-2,2'-disulfonate
      (DIDS)-sensitive component. A variety of chloride-channel inhibitors, other than
      DIDS, also blocked the chloride current, including 9-anthracenecarboxylic acid (9
      AC), niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and N
      phenylanthranilic acid (DPC). DIDS at 1 mmol l-1 and DPC at 2 mmol l-1 were both
      more potent than niflumic acid at 200 mumol l-1. The hyperosmotic condition (+50
      mosmol) did not affect the chloride current. The hypo-osmotic condition (-80
      mosmol), however, led to an increase of total membrane conductance, during which
      a chloride conductance increase occurred. The membrane-conductance increase,
      evoked by the hyposmotic condition, ran up and then ran down by itself. As with
      the steady-state chloride conductance, 1 mmol l-1 DIDS and 2 mmol l-1 DPC were
      more potent blockers than 200 mumol l-1 niflumic acid. DIDS at 1 mmol l-1 was
      more effective in blocking the outward component than 2 mmol l-1 DPC, while the
      inward component was blocked oppositely. When the intracellular calcium
      concentration was presumed to have increased, using the calcium ionophore,
      ionomycin, membrane conductance abruptly increased, quickly ran up and then ran
      down by itself. This included an elevation of a DIDS-sensitive current, and was
      largely carried by chloride. Chloride currents of rat RPE cells did not appear to
      be regulated by cyclic AMP.

PMID- 7513649
TI  - Nitric oxide in retina: relation to excitatory amino acids and excitotoxicity.
AB  - This study was undertaken to determine whether nitric oxide pathways exist in the
      retina and are linked to excitatory amino acid (EAA)-induced increases in cyclic
      guanosine monophosphate (cGMP). Exposure of embryonic day 15 chick retina for 5
      min to either 1 mM glutamate, 100 microM NMDA or 100 microM kainate (KA)
      increased cGMP content 2-3-fold. The putative environmental neurotoxins, domoic
      acid (DO, 20 microM), and beta-oxalyl-amino-L-alanine (BOAA, 200 microM), but not
      beta-methyl-amino-L-alanine (BMAA, 3 mM), also increased cGMP. The nitric oxide
      synthase inhibitor N-nitro-L-arginine (NNA) and nitric oxide scavenger,
      hemoglobin, completely blocked the increases in cGMP induced by the above
      glutamate-agonists. These glutamate agonist induced increases in cGMP were
      receptor mediated. MK-801, a NMDA receptor antagonist, blocked NMDA, and
      partially blocked glutamate-stimulated, cGMP formation. CNQX, a KA/AMPA receptor
      antagonist blocked cGMP increases produced by KA, BOAA and partially blocked
      those evoked by DO and glutamate. In order to examine the involvement of nitric
      oxide pathways in NMDA-mediated toxicity, the ability of NNA to protect against
      delayed excitotoxic damage caused by a 60 min exposure to NMDA was assessed.
      Delayed cell death, determined by LDH release and histology, following a 24 hr
      recovery period after NMDA treatment, was unchanged by the presence of NNA. NNA
      did not interfere with acute NMDA-stimulated GABA release indicating that NNA did
      not effect NMDA receptor interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513651
TI  - A murine stromal cell line promotes the proliferation of the human factor
      dependent leukemic cell line UT-7.
AB  - In long-term human bone marrow cultures, stromal cells of human origin are
      usually used on the assumption that human primitive progenitor cells do not
      respond to cytokines produced by stromal cells from other species. There is
      accumulating evidence, however, that murine stromal cells also promote
      maintenance and differentiation of very primitive human stem cells, which
      suggests the existence of novel stromal activities that cross species barriers.
      In this study, we show that a murine bone marrow-derived stromal cell line, MS-5,
      allows the proliferation of the human leukemic cell line UT-7. The long-term
      growth of UT-7 is usually supported only by human interleukin-3 (IL-3),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin
      (Epo). None of these three cytokines was involved in the observed effect, since
      murine GM-CSF and IL-3 do not act on human cells and MS-5 cells do not produce
      Epo. Soluble stem cell factor (SCF) induced UT-7 cell proliferation. However,
      S1/S1 mutant fibroblasts also supported UT-7 cell growth and anti-c-kit
      antibodies only partially abolished UT-7 cell proliferative response to MS-5
      cells. These observations excluded a major role of SCF in this system. MS-5
      derived growth-promoting activity was diffusible, but attempts to grow UT-7 cells
      in high levels of known soluble murine stromal-derived cytokines active on human
      cells showed no or minimal response, suggesting that MS-5's proliferative effect
      was not mediated by known cytokines. Finally, involvement of an autocrine loop of
      activation induced by MS-5 was excluded: RT-PCR analysis did not detect increased
      transcripts for GM-CSF, IL-3, IL-6, SCF, or Epo in UT-7 cells cocultured for 2 to
      6 days with MS-5. In addition, UT-7 cell proliferation on MS-5 was not inhibited
      by neutralizing antibodies against the human GM-CSF receptor or the human IL-6
      receptor alpha chain. Whether UT-7 cell proliferation triggered by MS-5 reflects
      the existence of novel stromal cytokines or results from synergistic interactions
      on the MS-5 cell surface between extracellular matrix proteins and cytokines will
      require further investigation.

PMID- 7513652
TI  - The relationship between different high proliferative potential colony-forming
      cells in mouse bone marrow.
AB  - Previous work has shown that part of the hierarchical structure of the
      hematopoietic system can be described by HPP-CFC-1 (primitive high proliferative
      potential colony-forming cells responding to colony-stimulating factor-1 [CSF-1]
      + interleukin-3 [IL-3] + IL-1), HPP-CFC-2 (more mature HPP-CFC responding to CSF
      1 + IL-3), and mature HPP-CFC responding to the single factors, CSF-1,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-3. In this
      study, we have attempted to relate the murine HPP-CFC, stimulated by various
      combinations of growth factors (GFs)--CSF-1, GM-CSF, IL-3, IL-6, IL-1, stem cell
      factor (SCF), and transforming growth factor-beta (TGF-beta)--and by CSF-1, GM
      CSF, and IL-3 on their own, to these known progenitors. Studies involving
      regeneration of the bone marrow after 5-fluorouracil (5-FU) treatment, generation
      of progenitors in liquid cultures in response to different GF combinations, and
      the HPP-CFC content of lineage-negative rhodamine-sorted bone marrow (BM)
      fractions have indicated that: 1. the combinations CSF-1 + IL-3 + IL-1 + SCF and
      CSF-1 + IL-3 + IL-1 + IL-6, and possibly CSF-1 + GM-CSF + IL-3 + IL-1, stimulate
      pre-HPP-CFC-1; 2. the combinations CSF-1 + IL-1 + GM-CSF, CSF-1 + IL-1 + IL-6,
      CSF-1 + IL-1 + SCF, CSF-1 + IL-3 + SCF, CSF-1 + IL-6 + SCF, and IL-3 + SCF,
      appear to overlap with the CSF-1 + IL-3 + IL-1 combination to stimulate the more
      mature cells of the HPP-CFC-1 compartment; 3. the combinations CSF-1 + GM-CSF,
      CSF-1 + IL-1, CSF-1 + IL-6, and CSF-1 + SCF may stimulate the more mature cells
      of the HPP-CFC-2 population, while the single factors CSF-1, GM-CSF, and IL-3, as
      suggested in other reports, may stimulate HPP-CFC that are more mature than the
      HPP-CFC-2; 4. the combinations IL-3 + IL-6 and SCF + IL-6 appear to stimulate HPP
      CFC that overlap with the HPP-CFC-1 population, while those responding to the
      combination GM-CSF + TGF-beta overlap with the HPP-CFC-2 population within the
      hematopoietic hierarchy; and 5. CSF-1 and GM-CSF appear to be interchangeable in
      the combinations studied.

PMID- 7513653
TI  - Local anesthetic lidocaine inhibits the effect of granulocyte colony-stimulating
      factor on human neutrophil functions.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced
      superoxide (O2-) release in human neutrophils stimulated by the chemotactic
      peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and inversely regulated
      the surface expression of cellular adhesion molecules, leukocyte adhesion
      molecule-1 (LAM-1) and CD11b/CD18 leukocyte integrin, on human neutrophils; that
      is, rhG-CSF downregulated the expression of LAM-1 and upregulated the expression
      of CD11b on neutrophils. The cationic local anesthetic lidocaine inhibited not
      only FMLP-induced O2- release in neutrophils but also FMLP-induced CD11b
      upregulation and LAM-1 downregulation on neutrophils in a dose-dependent manner.
      Lidocaine also abolished the priming effect of rhG-CSF for enhanced release of O2
      in neutrophils and inhibited rhG-CSF-induced CD11b upregulation and LAM-1
      downregulation on neutrophils in a dose-dependent manner. These findings suggest
      that lidocaine inhibits human neutrophil functions, such as adherence to
      endothelial cells, by interfering with the expression of cellular adhesion
      molecules on neutrophils, and that lidocaine might have anti-inflammatory
      properties by inhibiting the effect of inflammatory cytokines.

PMID- 7513654
TI  - Primary structure of bovine alpha 2-antiplasmin.
AB  - The primary structure of bovine alpha 2-antiplasmin (alpha 2AP) has been
      determined from cDNA and partial peptide sequencing. Mature bovine alpha 2AP
      contains 470 residues and is 6 residues longer than human alpha 2AP. Alignment of
      the two protein sequences show that 81% of their amino acid residues are
      identically located. Bovine alpha 2AP has 5 N-linked carbohydrate groups, of
      which four are found in human alpha 2AP (Asn105, 274, 288 and 295). Asn227 is the
      fifth carbohydrate attachement site in bovine alpha 2AP. The 3 Cys residues of
      bovine alpha 2AP are present as an unpaired residue (Cys131) and as a pair in a
      disulfide bridge (Cys49-Cys122). The assignment of the bridge in bovine alpha 2AP
      is at variance with the previous assignment of the two disulfide bridges in human
      alpha 2AP [Lijnen, H.R. et al. (1987) Eur. J. Biochem. 166, 565-574].

PMID- 7513655
TI  - Eutopic production of human chorionic gonadotropin beta (hCG beta) and
      luteinizing hormone beta (hLH beta) in the human testis.
AB  - The classical pregnancy and tumor marker hCG has long been considered to be only
      accidentally expressed ectopically, e.g. by tumors. The biological functions of
      low levels of hCG beta, hCG alpha and holo-hCG in the sera of nonpregnant healthy
      individuals remained unclear. Immunological analyses by our ultrasensitive time
      resolved fluoroimmunoassays revealed a concentration gradient from < 5 pg hCG
      beta/ml in cubital vein serum versus up to 480 pg hCG beta/ml in the
      corresponding benign testicular hydrocele fluids. Moreover, hCG beta and its
      cognate molecule luteinizing hormone beta (LH beta) were present in cytosolic
      extracts of normal human testes. Both hCG beta and hLH beta are eutopically
      produced as proven by RT-PCR and subsequent Southern and dot blot analyses. Thus,
      the view of a purely systemic hormonal function of hLH, and of hCG during
      pregnancy needs a reassessement as hCG beta and hLH beta are synthesized in the
      human testis and autocrine/paracrine actions seem to be likely.

PMID- 7513657
TI  - The regulation of sperm motility by a novel hyaluronan receptor.
AB  - OBJECTIVE: To determine if a novel receptor for hyaluronan, termed RHAMM, is
      responsible for the previously observed increase in sperm locomotion in response
      to hyaluronan and to assess whether expression of the RHAMM protein is involved
      in sperm motility. DESIGN: The RHAMM protein was localized on human sperm by
      immunofluorescence of fixed cells, fluorescence-activated cell sorter (FACS) of
      cell surface phenotype, and Western transblot analysis of cell proteins. The
      effect of monospecific antibodies on sperm motility was examined using computer
      assisted image analysis. Results of motility studies were assessed statistically
      with analysis of variance. SETTING: Samples were collected from donors from the
      University of Manitoba donor insemination program. SUBJECTS: Semen was collected
      twice from four participants and a total of 10,000 sperm per sample were
      evaluated. RESULTS: A hyaluronan receptor, RHAMM, was localized by
      immunofluorescence along the tail, the midpiece, and the head of sperm. Positive
      staining obtained with FACS analysis indicated that RHAMM occurred on the surface
      of sperm, whereas immunoblot analysis of sperm cell lysates revealed RHAMM
      proteins of MWE 58 and 64 kd, consistent with the size of RHAMM localized from
      fibroblasts. A polyclonal antibody specific to a peptide encoded in the
      fibroblast RHAMM complementary DNA significantly decreased the motility of sperm.
      Analysis of this inhibition is consistent with an effect of the antibody on
      flagellar function. CONCLUSIONS: The presence of RHAMM on sperm surfaces and the
      ability of monospecific antibodies to inhibit sperm motility suggest an important
      role for this novel glycoprotein in sperm motility.

PMID- 7513656
TI  - High doses of oral contraceptives do not alter endometrial alpha 1 and alpha v
      beta 3 integrins in the late implantation window.
AB  - OBJECTIVE: To assess the effects of an emergency contraceptive agent on the
      distribution of integrin heterodimers during that part of the implantation
      window. DESIGN: Prospective, case-controlled study in a university-based
      Population Program. In the first ovulatory control cycle after the detection of
      LH surge, patients had endometrial sampling 11 days after the surge. In the next
      cycle the procedure was repeated 2 days after the administration of a postcoital
      contraceptive agent on day 9 after LH surge (100 g ethinyl E2 and 2 mg
      norgestrel). MAIN OUTCOME MEASURES: The effects of postcoital contraceptives on
      the expression of integrin heterodimers (alpha 1 and alpha v beta 3 subunits)
      reported to be unique to secretory phase was determined. RESULTS: All six
      specimens were consistent histologically with days 24 and 25 of the menstrual
      cycle by light microscopy. Using immunohistochemistry, strong membrane staining
      of endometrial glandular cells and superficial epithelium for both alpha 1
      subunit and vitronectin (alpha v beta 3) receptor was observed in treatment and
      controls. No diminution of intensity or distribution was observed relative to
      pretreatment controls. CONCLUSIONS: There is no apparent change in the level of
      these two integrins in the human endometrium when high-dose oral contraceptives
      are given in the later stages of the implantation window. This suggests that the
      high doses of steroids used in emergency contraceptives may exert their effect
      through more complex mechanisms than endometrial cell surface changes.

PMID- 7513659
TI  - Developmental potentials of enteric neural crest-derived cells in clonal and mass
      cultures.
AB  - The aim of this work was to test the differentiation capacities of neural crest
      derived cells that had already migrated to the gut and were in the process of
      forming the intrinsic gut plexuses, when they were withdrawn from the gut wall
      environment. The experiments were performed on the quail bowel of embryos at 4 to
      12 days of incubation (E4 to E12), which was dissociated into a single cell
      suspension. The crest cells invading the gut carry the NC1/HNK1 epitope. This
      allowed us to select them as singlets under the control of a uv-illuminated
      inverted microscope. Crest-derived cells from the gizzard were then clonally
      cultured on a feeder layer of growth-inhibited 3T3 fibroblasts, as described
      before for cephalic and truncal neural crest cells. The clonal efficiency of
      these cells reached about 28% from E4 to E7 and decreased sharply at E8. The size
      of the clones generated by cells taken between E4 to E8 varied considerably.
      Large clones (> 10(3)) were numerous from E4 and E5 gizzard-derived cells,
      whereas E7 and E8 cells produced only very small colonies. The phenotypic
      diversity of the clones decreased similarly during the time period under
      scrutiny. Two phenotypes never encountered in the enteric plexuses were found in
      the cultures: adrenergic cells and glial cells expressing SMP, a marker
      exclusively expressed by Schwann cells in vivo and normally absent in enteric
      glia. The capacity to yield adrenergic cells was present up to E6 in clonal
      cultures of gizzard neural crest-derived cells. Mass cultures of cells
      dissociated from the gizzard and bowel, including gut mesenchymal and epithelial
      cells in addition to cells of neural crest origin, revealed that both adrenergic
      and SMP+ cells could arise under these conditions even in a defined culture
      medium devoid of serum and chick embryo extract. The number of TH+ cells
      developing in bowel cultures reached a peak at E7, while at this stage no TH+
      cells could be obtained from gizzard cultures. A craniocaudal gradient of
      disappearance of adrenergic precursors in the gut could thus be demonstrated.
      Finally we point out that these and previous experiments from other laboratories
      show that precursor cells of the sympathoadrenal lineage are present in all types
      of avian sensory and autonomic ganglia during development even though, in most of
      them, these cells never express the adrenergic phenotype.

PMID- 7513660
TI  - Immunolocalization of basement membrane components and beta 1 integrin in the
      chick wing bud identifies specialized properties of the apical ectodermal ridge.
AB  - To examine whether the extracellular matrix (ECM) plays a role in mediating
      interactions between the apical ectodermal ridge (AER) and the subjacent mesoderm
      in the chick wing bud, we used immunohistochemistry to locate the following
      tissue components during wing morphogenesis: types I and IV collagens,
      fibronectin, the basal lamina form of heparan sulphate proteoglycan (HSPG),
      laminin, and the beta 1 integrin subunit. The notch region at the base of the AER
      exhibits particularly strong labelling for type IV collagen, fibronectin,
      laminin, and beta 1 integrin. This suggests that the ridge cells are firmly
      anchored to their underlying basement membrane. In nonridge ectoderm, the beta 1
      integrin subunit is present only at the basal cell surface, whereas in the AER it
      has a pericellular distribution. The localization of beta 1 integrin receptors at
      the lateral ridge cell surfaces, in the apparent absence of fibronectin,
      collagens I and IV, and laminin, suggests that they may function in cell-cell
      adhesion in the AER. The normal AER-mesenchyme interface was compared to an
      experimental situation in which the AER flattens. This was induced in the
      anterior region of the wing bud by inserting an impermeable barrier at
      intersomite level 17/18, at stage 21. At 12 hr (stage 23) and 24 hr (stage 25)
      after the operation, each of the ECM components listed above is uniformly
      distributed along the experimental epithelial-mesenchymal interface. By 24 hr
      postoperation, the beta 1 integrin subunit is restricted to the basal surface of
      the flattened apical ectoderm. Similar changes occur in the AER as it flattens
      during later stages of normal development. These results point to a possible role
      for the ECM and integrin receptors in maintaining the thickened structure of the
      AER.

PMID- 7513658
TI  - Management of early ectopic pregnancy.
AB  - OBJECTIVE: Management of early ectopic pregnancy was investigated in a
      multicenter, prospective study. METHODS: Serum beta-hCG levels were monitored
      after therapy and correlated to the type of management, gestational age, and
      initial serum beta-hCG levels in 119 patients with ectopic pregnancies detected
      at 5-7 postmenstrual weeks. RESULTS: Salpingectomy was performed in 16 patients.
      No post-operative complications were reported. After conservative laparoscopic
      surgery of 51 ectopic pregnancies, 9 (18%) had delayed decrease or an increase of
      serum beta-hCG levels. Re-operations were performed in 4 (7%) patients. Similar
      findings were noted in 2/6 patients after conservative operations performed by
      laparotomy. Intrachorionic injection treatment was successful in 17/18 ectopic
      pregnancies, and expectant management in 7/8 patients with initial serum beta-hCG
      levels below 250 mIU/ml. CONCLUSIONS: Persistence of trophoblastic activity is a
      potential complication of conservative surgical treatment of ectopic pregnancy. A
      detailed diagnosis as early as 6-7 post-menstrual weeks may be the key for future
      non-surgical management of ectopic pregnancy.

PMID- 7513662
TI  - [Characteristics and role of peptides with action on the cardiovascular system].

PMID- 7513661
TI  - Testing for HCV markers.
AB  - Until 1988 the putative agent of non-A/non-B (NANB) hepatitis had not been found.
      Research workers of the Chiron Corporation (California, USA) then identified, by
      "blind expression cloning", polypeptides which specifically bound antibodies
      present in sera of NANB-patients. A fusion polypeptide (C-100) was expressed in
      yeast. With the C-100 antigen prototype RIA and ELISA antibody tests were
      developed. Subsequently more polypeptides (C-200, C33c, C22) of the HCV-genome
      were added to the test system, resulting in second generation anti-HCV tests with
      increased sensitivity. For confirmation of HCV ELISA reactive samples,
      recombinant immunoblot (RIBA-2, Ortho; Innolia, Innogenetics) and dot immunoblot
      assays (Matrix, Abbott) were developed. Detection of HCV antigens has been
      hampered by the low virus titres in serum and the absence of free circulating
      viral antigen(s). However, with cDNA-PCR, applying primers of the highly (> 93%
      nucleotide homology) conserved 5' untranslated (5'UTR) region of the HCV genome,
      HCV-RNA in serum as well as in liver tissue can be detected. cDNA-PCR, although
      not yet commercially available, is useful to confirm HCV-viremia in patients.
      When chronic hepatitic C patients are treated with anti-viral drugs, the
      disappearance of HCV-RNA, as detected by PCR, is a measure of therapy response.

PMID- 7513664
TI  - Protective function of extrinsic sensory neurons in acute rabbit experimental
      colitis.
AB  - BACKGROUND/AIMS: Sensory nerves appear to have a protective effect against acute
      injury in the gastric mucosa. Their function in the intestine is unclear.
      METHODS: In this study an immune-complex model of colitis was used to induce
      inflammation in the distal colon with and without functional ablation of sensory
      neurons by capsaicin pretreatment. RESULTS: Colitis was more severe in the
      capsaicin-pretreated group than in the vehicle group 48 and 96 hours after
      induction of colitis. Neutrophil infiltration, expressed as inflammatory index,
      was significantly increased to 4.25 +/- 0.4 vs. 1.83 +/- 0.5 at 48 hours and to
      2.66 +/- 0.6 vs. 1.65 +/- 0.3 at 96 hours in the capsaicin group and the vehicle
      group, respectively. The microscopic ulcer index also was significantly increased
      in the capsaicin-pretreated group compared with the vehicle group (63.3 +/- 10.6
      vs. 3.3 +/- 2.4 at 48 hours, 20.0 +/- 8.4 vs. 1.5 +/- 1.1 at 96 hours).
      Immunoreactive substance P (SP) and calcitonin gene-related peptide (CGRP)
      contents were decreased in extracts of inflamed compared with uninflamed colon.
      CONCLUSIONS: These data suggest that sensory neurons have a protective role in an
      acute rabbit model of experimental colitis by release of sensory neuropeptides
      (SP, CGRP), which may modulate vascular tone and mucosal blood flow.

PMID- 7513663
TI  - Rat cluster of differentiation 1 molecule: expression on the surface of
      intestinal epithelial cells and hepatocytes.
AB  - BACKGROUND/AIMS: Cluster of differentiation 1 (CD1) is a family of
      nonpolymorphic, major histocompatibility complex class I-like molecules with
      prominent expression in the liver and intestinal epithelium of humans and mice.
      Models of intestinal and hepatobiliary inflammation and experimental liver
      transplantation are conducted in the rat, yet nothing is known of CD1 expression
      in this species. METHODS: Monoclonal antibodies against murine CD1 were used to
      identify a rat CD1 homologue. Tissue messenger RNA expression was confirmed by
      Northern blot analysis with a murine CD1 complementary DNA probe. RESULTS:
      Immunoperoxidase staining detected CD1 in intestinal epithelial and liver cells
      but not in the thymus. Immunofluorescence of isolated hepatocytes and a rat fetal
      intestinal cell line, SLC-44, showed cell surface expression of CD1. Metabolic
      labeling and immunoprecipitation of the SLC-44 cell line and a mouse intestinal
      epithelial cell line, MODE-K, showed a protein of 55 kilodaltons. Immunoblotting
      of CD1 in isolated intestinal epithelial cells and hepatocytes showed a molecule
      of 55 kilodaltons. Northern blot analysis showed a single message of
      approximately 2.2 kilobases in hepatocytes. CONCLUSIONS: A CD1 homologue exists
      in the rat. Expression in the rat intestine and liver are similar to those in the
      human and mouse. The rat may be useful as a model for the study of CD1 function.

PMID- 7513666
TI  - Fibroblast growth factors modulate intestinal epithelial cell growth and
      migration.
AB  - BACKGROUND/AIMS: Various peptide growth factors have been found to exert
      functional effects among epithelial cell populations. This study assessed the
      role of certain fibroblast growth factors (FGFs) (acidic FGF, basic FGF, and
      keratinocyte growth factor) in the regulation of intestinal epithelial cell
      proliferation and restitution. METHODS: Recombinant growth factors were added to
      subconfluent cultures of IEC-6, Caco-2, and HT-29 cell lines with subsequent
      assessment of [3H]-thymidine incorporation. The effects on an in vitro model of
      restitution were assessed by quantitation of cells migrating into standard wounds
      established in confluent monolayers of IEC-6 cells. Transforming growth factor
      beta (TGF-beta) content of growth factor-treated wounded monolayers was assessed
      by Northern blot and bioassay. RESULTS: Acidic FGF, basic FGF, and keratinocyte
      growth factor caused a modest increase in proliferation of IEC-6, Caco-2, and HT
      29 cell lines. Acidic FGF and basic FGF promoted intestinal epithelial cell
      restitution in vitro up to 10-fold, in conjunction with the enhanced expression
      of TGF-beta messenger RNA and protein. Promotion of IEC-6 restitution by acidic
      and basic FGF could be blocked by addition of immunoneutralizing anti-TGF-beta
      antisera. CONCLUSIONS: FGFs that exert effects on fibroblast cells also exert
      effects on intestinal epithelial cell populations and may help promote epithelial
      cell restitution, the initial step of intestinal wound healing through a TGF-beta
      dependent pathway.

PMID- 7513665
TI  - Normal colonic epithelium adheres to carcinoembryonic antigen and type IV
      collagen.
AB  - BACKGROUND/AIMS: Human colorectal carcinoma cells bind to collagen and laminin in
      the basement membrane as well as to carcinoembryonic antigen (CEA) on neighboring
      cells. The purpose of this study was to determine whether normal colonic
      epithelial cells bind to CEA, collagen, or laminin. METHODS: Intact colonic
      crypts were isolated from normal mucosa in 13 specimens resected for colorectal
      carcinoma or colonic diverticulitis. Colonocytes were released from the crypts by
      treatment with collagenase and deoxyribonuclease and tested for adhesion to CEA,
      type IV collagen, and laminin in a solid-phase adhesion assay. RESULTS: Twelve
      percent to 25% of colonocytes in all specimens bound to CEA. Colonocytes from
      seven specimens also bound to type IV collagen, but none of the colonocyte
      preparations bound significantly to laminin. Monoclonal antibodies to CEA and to
      the hyaluronate receptor CD44 and enzymatic removal of membrane CEA blocked the
      adhesion of colonocytes to CEA. CONCLUSIONS: First, colonocytes use the same
      epitopes on CEA and CD44 as colorectal carcinoma cells to adhere to solid-phase
      CEA. Second, colonocytes bind to solid-phase CEA through CEA-to-CEA homophilic
      binding. Third, CEA and type IV collagen, but not laminin, are adhesion ligands
      for human colonocytes.

PMID- 7513668
TI  - Intermediate filaments in rat pancreatic acinar tumors, human ductal carcinomas,
      and other gastrointestinal malignancies.
AB  - BACKGROUND/AIMS: Keratin is a member of the intermediate filament family in
      epithelial cells. Two-dimensional gel electrophoresis of different epithelial
      cells has shown 20 different keratin polypeptides. Therefore, mapping of the
      keratin polypeptides can be used to define a specific tissue. METHODS:
      Cytokeratin expression was investigated by using monoclonal antibodies in human
      surgical specimens and autopsy material of pancreatic, gastric, liver, and colon
      carcinomas and cholangiocarcinomas, and their metastasis to lymph nodes and liver
      was examined. In addition, rat acinar cell carcinomas were used to compare
      cytokeratin expression in ductal vs. acinar cell pancreatic carcinomas. RESULTS:
      Human pancreatic ductal carcinomas expressed keratins 7, 8, 18, and 19, whereas
      the majority of rat acinar carcinomas did not express keratins typical for ducts
      in rat pancreas. The keratin patterns of gastric and colon carcinomas were
      identical with keratins 8, 18, and 19. In contrast, hepatocellular carcinomas
      expressed the same keratin pattern as pancreatic acinar carcinomas with keratins
      8 and 18, whereas cholangiocarcinomas expressed keratin 7, 8, 18, and 19, similar
      to pancreatic ductal carcinomas. Metastasis of pancreatic ductal and colon
      carcinomas retained their keratin patterns. CONCLUSIONS: Keratin polypeptide
      typing of unknown malignant cells can be a useful tool for cell identification.

PMID- 7513669
TI  - [Surgical secondary measures in unsuccessful prostaglandin treatment of tubal
      pregnancy].
AB  - As local drug treatment grew more common, the risk of persisting trophoblast
      remnants increased in tubal pregnancies treated in this way. We studied the
      secondary surgical measures in 52 patients, who had to undergo surgery for a
      second time after tubal pregnancy treated with prostaglandins. The indication for
      revision was arrived at 30 times on the basis of laboratory parameters
      (increasing or constant beta-HCG) (Group I). Reoperation had to be performed 22
      times because of acute clinical symptoms (Group II). Laparotomy was performed 40
      times, repelviscopy 12 times. In patients of Group I, the rate of rupture, that,
      had already occurred at the time of secondary surgery, was significantly smaller
      (p < 0.0001); in that case secondary surgery was significantly more often
      successful (p < 0.06) in preserving the tubes. In case of constant beta-HCG
      values 11 patients (50% of Group II) developed acute symptoms; another 7 patients
      (31.8%) also had to be reoperated on due to acute complaints, although the values
      were already clearly reduced. The study proves, that tubal pregnancies can be
      reoperated with preservation of the tubes even after unsuccessful prostaglandin
      therapy. The starting position for secondary surgery with preservation of the
      tubes is much better before acute clinical symptoms occur.

PMID- 7513670
TI  - GnRH and substance P regulate prostaglandins and sex steroids from reptilian
      (Podarcis sicula sicula) ovarian follicles and corpora lutea.
AB  - The in vitro effects of salmon gonadotropin-releasing hormone (sGnRH), substance
      P (SP), and their antagonists on prostaglandin F2 alpha (PGF2 alpha),
      prostaglandin E2 (PGE2), progesterone, androgens, and estradiol-17 beta release
      by follicles and corpus luteum (CL) of the oviparous lizard, Podarcis sicula
      sicula, were studied. Follicles and CL were divided according to the different
      developmental stages; follicles: pre-vitellogenic, early-vitellogenic, mid
      vitellogenic, and fully grown; CL: CL1 (unshelled eggs in the oviducts), CL2
      (shelled eggs in the oviducts), CL3 (eggs laid 6 hr previously), and CL4 (eggs
      laid 48 hr previously). SGnRH increased PGF2 alpha and progesterone release by
      mid-vitellogenic and fully grown follicles; SP increased PGE2 and estradiol-17
      beta release by pre-vitellogenic, mid-vitellogenic, and fully grown follicles.
      SGnRH and SP decreased PGE2 and progesterone and increased PGF2 alpha by CL1 and
      CL2. The antagonists of these two neuropeptides induced the opposite effects of
      those of sGnRH and SP. The present data indicate that sGnRH and SP play different
      roles in the regulation of prostaglandins and sex steroid production by ovarian
      follicles and CL of P. s. sicula.

PMID- 7513671
TI  - Cell-free synthesis of vitellin in the shrimp Penaeus semisulcatus (de Haan).
AB  - The vitellogenic ovary of Penaeus semisulcatus contains mRNA specific for
      vitellin (Vt), low levels of which are found in nonvitellogenic ovaries, and is
      absent from testes. Immunoisolation from cell-free translation of poly(A)+ RNA
      using antiserum against purified Vt produced a 35-kDa polypeptide. No differences
      were found between Vt precipitated from the translation products of the rabbit
      reticulocyte system and that from the wheat germ extract. The specificity of the
      immunoprecipitation reaction was demonstrated by the absence of precipitation
      with nonimmunized rabbit serum and with antibodies prepared against purified
      hemocyanin or lipoprotein I (LPI), which are crustacean hemolymph proteins. In
      addition, competition with the radioactively labeled translation product occurred
      only in the presence of purified Vt, but not BSA or LPI. Vt synthesized in the
      translation system had a significantly lower molecular weight than that of the
      purified Vt or that synthesized by ovaries incubated in vitro. The possibility
      that this difference may be because of the non-glycosylated nature of a cell-free
      translation product was tested. The removal of oligosaccharides from purified Vt
      by enzymatic digestion with N-glycosidase F resulted in the appearance of a
      smaller polypeptide of 36 kDa, which reacted immunologically with Vt antiserum in
      a Western blot. The size of this fragment is very close to the molecular weight
      of the translation product.

PMID- 7513667
TI  - Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver
      damage.
AB  - BACKGROUND/AIMS: Mixed cryoglobulinemia is frequently associated with liver
      diseases. The respective role of hepatitis C virus (HCV) and liver damage in the
      pathogenesis of cryoglobulinemia is investigated in this study. METHODS: The
      prevalence of cryoglobulinemia in 226 consecutive patients with chronic liver
      diseases (hepatitis C, 127; hepatitis B, 40; other diseases, 59) was studied, and
      the epidemiological, biological, histological, and virological features in these
      three groups were analyzed. Anti-HCV antibodies, HCV proteins, and HCV RNA were
      searched in the cryoprecipitates. RESULTS: The prevalence of mixed
      cryoglobulinemia was high (41.5%) in patients with liver diseases and higher in
      patients with hepatitis C (54.3%) than in patients with hepatitis B (15%) or
      other causes of liver disease (32%). Patients with cryoglobulinemia had cirrhosis
      more frequently and had a longer history of hepatitis. In patients with hepatitis
      C, HCV RNA sequences and HCV proteins were detected in the cryoprecipitate.
      Cryoglobulins became undetectable in 21 of 43 patients treated with interferon.
      CONCLUSIONS: These findings suggest that HCV is a major cause of
      cryoglobulinemia. Besides viral infection itself, multiple factors appear to be
      responsible for the production of cryoglobulins, including cirrhosis and duration
      of liver disease.

PMID- 7513673
TI  - Triple immunofluorescence evaluation of CD15, CD34 and class II expression by
      flow cytometry in normal and leukemic bone marrows.
AB  - BACKGROUND: The CD15/CD34 phenotype has been reported as aberrant and exploited
      for monitoring minimal residual disease in acute myeloid leukemia (AML) patients.
      Moreover, CD15/CD34 has been described as a rare phenotype in normal bone marrow
      (NBM) (< 0.10%). We used a triple immunofluorescence assay to investigate the
      expression of CD15, CD34 and class II antigens in normal (NMB) and leukemic (LBM)
      bone marrows. METHODS: A FACScan for quantitative fluorescence and the PAINT-A
      GATE program for multiparametric analysis were utilized. Fifteen normal bone
      marrow and fifteen leukemic bone marrow samples were studied with a triple
      immunofluorescence assay. A FACSorter was used for sorting. RESULTS: Eleven out
      of 15 normal marrows contained less than 0.67% (range 0.01-0.66) cells which
      coexpressed CD15, CD34 and class II antigens. Three normal marrows contained more
      than 0.67% but less than 1.84% (range 1.05-1.83) triple stained cells. The entire
      group of leukemic marrows coexpressed triple stained cells with a frequency
      higher than 1% (range 1.1-48.6); furthermore, 10 samples contained the same
      population at frequencies higher than 10%. The difference between normal and
      leukemic marrows was statistically significant (p = < 0.001). Triple positive
      cells (TPc) from NBM were sorted for morphology, which proved to be consistent
      with myeloid progenitor features (early myeloblasts). This confirms that CD15+
      CD34+ Class II+ precursors are commonly expressed in NMB, although at low
      frequency. Interestingly, 12 (80%) AMLs out of 15 were diagnosed as M1 (5) or M2
      (7), while the remaining were M4 (2) and M5a (1). Additionally, all M2 cases were
      positive at percentages higher than 10%. Apparently CD15, CD34, class II
      expression correlates mainly with granulocyte differentiation. Two complete
      remission (CR) LBM, positive at onset for the triple combination, were regularly
      monitored. In one case the TPc percentage always remained near the normal values
      found in NBM (0.72%), and this patient is still in CR. In the other, overt
      relapse was preceded by a progressive increase in the TPc percentage.
      CONCLUSIONS: Although the presence in NBM of CD15+ CD34+ and class II+ precursors
      hinders minimal residual disease detection, we conclude that this unusual
      combination may distinguish a leukemic population and may allow monitoring of
      "early relapse".

PMID- 7513675
TI  - Autologous transplantation of peripheral blood progenitor cells mobilized by
      chemotherapy with or without G-CSF (filgrastim) in resistant lymphoproliferative
      diseases: enhanced hemopoietic recovery with filgrastim primed progenitors.
AB  - BACKGROUND AND METHODS: Bone marrow transplantation is increasingly used to
      overcome the bone marrow toxicity from myeloblative therapy. Peripheral blood
      progenitor cell transplantation (PBPCT) has been recognized as an alternative
      source of bone marrow for hemopoietic recovery after myeloblative therapy. In the
      steady state condition hemopoietic progenitors are scarce in peripheral blood;
      chemotherapy and growth factors are both able to increase PBPCs. Twenty-five
      patients affected by resistant lymphoproliferative diseases [4 multiple myeloma
      (MM), 19 non Hodgkin's lymphoma (NHL) and 2 Hodgkin's disease (HD)] were
      submitted to autologous peripheral blood progenitor cell transplantation (PBPCT).
      PBPCs were collected after chemotherapy (CT) alone (8 patients) or plus
      filgrastim (17 patients). Filgrastim was not administered after PBPCT in any
      case. RESULTS AND CONCLUSIONS: A statistically significant difference between the
      two groups was found for the following parameters: number of leukaphereses
      administered, amount of CFU-GM infused, time to hemopoietic recovery, amount of
      supportive care, number of days of antibiotic therapy, length of hospitalization.
      PBPCs primed with filgrastim CT appeared to be markedly superior to CT-recruited
      PBPCs in reducing the period of neutropenia and, surprisingly, of
      thrombocytopenia. Reduction in hematologic toxicity resulted in a decrease of
      transplantation-related toxicity and mortality, even in elderly and/or heavily
      pretreated patients.

PMID- 7513674
TI  - VNCOP-B regimen in the treatment of high-grade non-Hodgkin's lymphoma in the
      elderly.
AB  - BACKGROUND: Age is an important factor, especially in patients with advanced
      lymphoma who require more intensive and extensive therapy for any possible chance
      of cure. In fact, attenuation of treatment to diminish treatment-related toxicity
      decreases the capacity of the therapy to effect a cure. METHODS: Between
      December, 1991 and February 1993, 29 previously untreated patients 60 years and
      older with high-grade non-Hodgkin's lymphoma (HG-NHL), according to the Kiel
      classification, were treated with a combination therapy including
      cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone
      (VNCOP-B). RESULTS: Twenty-two patients achieved a complete pathologic remission
      and 5 had a partial response, with a reduction of more than 50% of tumor-related
      manifestations. Only two cases were resistant to VNCOP-B. Overall survival was
      75%, with a median follow-up of 13 months from diagnosis; four of the patients
      who achieved complete response relapsed after a median follow-up of 11 months
      from the completion of treatment. Clinical and hematologic toxicity was
      irrelevant: in 12 patients, neutropenia was responsible for a temporary
      interruption of therapy for 1-2 weeks. CONCLUSIONS: This regimen was effective in
      inducing a good remission rate with moderate toxic effects in elderly patients
      with HG-NHL, but a longer follow-up is warranted before definitive conclusions
      can be drawn.

PMID- 7513672
TI  - Symptom relief and quality of life after stenting for malignant bile duct
      obstruction.
AB  - Palliative treatment is appropriate for most patients with cancer of the head of
      pancreas. Insertion of a biliary stent relieves jaundice and pruritus but it is
      not known if stenting affects other symptoms or changes the quality of life.
      Nineteen patients have completed a standard questionnaire to assess symptom
      relief and quality of life after stent insertion. After stenting there was
      complete relief of jaundice and pruritus. Furthermore, there was also
      considerable improvement in anorexia and indigestion. All patients had anorexia
      before stent insertion, this was moderate/severe in 13 (68.4%). Anorexia was
      significantly better (p < 0.01) a week after stenting and this benefit was
      maintained at 12 weeks (p < 0.01). Sixteen (84.2%) patients complained of
      indigestion before stenting, moderate/severe in 11 (57.9%). This was
      significantly better (p < 0.01) a week after stenting with complete relief in six
      at eight weeks (p < 0.01). Fifteen (78.9%) felt that their mood was good/very
      good before stent insertion and this was unchanged even at the 12 week
      assessment. A similar result was obtained for physical health and level of
      activity. In conclusion stent insertion not only relieves jaundice and pruritus
      in these patients but also improves other symptoms and quality of life. The
      considerable improvement in appetite after stenting was of particular benefit.

PMID- 7513676
TI  - A new method for palliation of malignant obstructive jaundice utilizing a
      peritoneo-venous shunt pump.
AB  - A new simple palliative method for use in malignant obstructive jaundice is
      presented. This method is particularly effective in the prevention of ascending
      infections. The method consists of interposing a one-way flow shunt pump
      (peritoneo-venous shunt pump) between a bile catheter and a jejunal catheter.
      Four patients were treated with this new method. Jaundice improved significantly
      in all patients. They had a much better quality of life with no serious
      complications during the terminal course. This less invasive and safe procedure
      is preferred for patients who have extrahepatic biliary obstruction due to
      incurable malignant tumors.

PMID- 7513677
TI  - Transarterial oily chemoembolization for the treatment of hepatocellular
      carcinoma: a multivariate analysis of prognostic factors.
AB  - A total of 84 patients with hepatocellular carcinoma and cirrhosis were analyzed
      retrospectively to investigate prognostic factors. All patients received
      transarterial oily chemoembolization as the only anticancer therapy. The follow
      up range was 1 to 39 mo (median, 9.5 mo). The overall actuarial survival rates at
      12, 24 and 30 mo were 62%, 31% and 24%, respectively. According to univariate
      analysis, variables significantly associated with survival were age, Child-Pugh
      grade, total serum bilirubin, Okuda stage, tumor size, degree of labeling of the
      tumor with Lipiodol, gelatin foam use, changes with treatment in tumor size and
      changes with treatment in alpha-fetoprotein concentration. Two multivariate
      analyses were performed. When pretreatment and treatment variables were
      considered, parameters with independent prognostic value were age, Child-Pugh
      grade, total serum bilirubin, tumor size and degree of Lipiodol labeling of the
      tumor. When follow-up variables were also considered, we (a) confirmed the
      prognostic significance of all these parameters (age, Child-Pugh grade, total
      serum bilirubin, tumor size) and (b) found the independent prognostic value of
      the change in tumor size (or change in alpha-fetoprotein concentration). Both
      models yielded different risk coefficients for each class of each variable. Two
      simple prognostic indexes, based on these coefficients, are proposed: an
      "initial" index (including pretreatment and treatment variables) and a "follow
      up" index (also including follow-up variables). According to the two indexes, the
      patients were classified into three groups with different prognoses: good (93%
      and 100% actuarial survival at 1 yr for the initial and follow-up indexes,
      respectively), intermediate (65% and 53%, respectively) and poor (27% for both
      indexes).

PMID- 7513679
TI  - Predeposit autologous blood transfusion in elderly patients undergoing
      transurethral resection of the prostate.
AB  - In order to reduce the rate of homologous blood transfusion, predeposit
      autologous blood transfusion has been introduced in 134 out of 266 patients
      undergoing transurethral resection of the prostate since February 1988. Nine
      (6.7%) out of 134 patients who deposited their own blood were also transfused
      with homologous blood. In contrast, the rate of homologous blood transfusion was
      22.7% in 132 patients who did not deposit autologous blood. Overall homologous
      blood transfusion rate (14.7%) in the past 4.5 years has been much lower than in
      the previous 4 years (22.2% in 203 patients). In 6 patients in whom blood
      donation was performed concurrently with administration of recombinant human
      erythropoietin, decrease of haemoglobin level was significantly less than in
      those without rHuEPO. Predeposit autologous blood transfusion can reduce
      homologous blood transfusion rate. It is safe and easily performed, and more
      effective when combined with rHuEPO administration even in elderly patients
      undergoing TURP.

PMID- 7513678
TI  - Experience in treating benign prostatic hypertrophy with Sabal serrulata for one
      year.
AB  - The authors treated 42 BPH patients with the Sabal extract Strogen forte for 12
      months. The obstructive symptoms, residual volume, mean and maximum flow rates
      improved significantly by the 6th therapeutic month at the latest. The results
      seem to prove the effectiveness of the drug. Side effects have not been observed.

PMID- 7513680
TI  - [Therapy of hypopharyngeal cancer. Part IV: Long-term results of transoral laser
      microsurgery of hypopharyngeal cancer].
AB  - Between 1979 and 1986, 74 patients with hypopharyngeal carcinomas were operated
      using transoral laser microsurgery by the first author. 32 of the patients were
      subdivided into 5 subgroups and considered separately because of pretreatment for
      head and neck tumors, simultaneous multiple tumors etc. (excluding criterias).
      Survival times were not significantly prolonged and lasted 1-27 months (median,
      11 months), but the quality of life was improved due to preservation or
      restoration of natural laryngopharyngeal functions. Forty-two patients were
      operated with curative intention. This group primarily underwent transoral laser
      microsurgery, aiming at complete locoregional tumor resection with function
      preservation (pT1, 5; pT2, 31; pT3, 4; pT4, 2). In 29 patients 31 necks were
      operated, mostly as a regionally limited functional neck dissection (or
      "selective" neck dissection). In 90% of the cases neck metastases (pN+) were
      found, mostly in levels II and III; pN1, 6; pN2a, 1; pN2b, 18; pN2c, 1.
      Altogether, stages III and IV were found in 71.4% of the patients. A temporary
      tracheotomy was required in four patients. There was no secondary laryngectomy,
      even though it was indicated in one case. Post-treatment oncological followup
      (median observation time, 104 months) demonstrated loco-regional recurrences (n =
      1), late or recurrent metastases (n = 4), persisting metastases in the neck with
      cerebral metastasis (n = 1), distant metastases (n = 4), secondary tumors (n = 9,
      5 of which occurred in the head and neck). Through March 1993, 24 patients (57%)
      have died. Causes were TNM-related (7), second primary tumor with or without
      distant metastases (8) and intercurrent disease with no evidence of disease (9).
      Within 5 years 17% of the patients died of TNM-related tumors, 9.5% due to a
      second primary with or without distant metastases, as well as 9.5% with
      intercurrent disease. The 5-year overall survival rate was 64% and was 83%
      (adjusted survival rate) if only TNM-related deaths were considered.

PMID- 7513681
TI  - A cytotoxic human hybridoma monoclonal antibody (TrJ6) defining an epitope
      expressed by HLA-DQ4 and -DQ5.
AB  - We have generated a cytotoxic human hybridoma monoclonal IgM lambda antibody,
      designated TrJ6, that is specific for a new epitope shared by HLA-DQ4 and -DQ5.
      TrJ6 strongly killed all ten DQ4-bearing cells and weakly killed all four DQ5
      bearing cell lines. In contrast, none of the 36 cell lines lacking DQ4 and DQ5
      antigens was recognized by TrJ6. This was confirmed by fluorescence cytometry.
      The specific binding of TrJ6 to a DQ4-bearing line was efficiently blocked by
      IIB3 (murine anti-DQ8+9+4+5+6 mAb) and TrG6 (human IgG mAb against DQ4+5+6),
      confirming that TrJ6 is specific for a polymorphic DQ epitope. TrJ6 can be used
      to distinguish DQ5+ from DQ6+ B-lymphoblastoid cells. DQ4 beta and DQ5 beta
      chains share one unique residue (Ser-74) and one relatively unique residue (Val
      75), which may therefore need to be coexpressed in order for the TrJ6 epitope to
      be formed. Alternatively, Ser-74 alone contributes critically to the
      allospecificity of this epitope. In addition, one or more of three residues
      unique for DQ4 (Leu-56, Glu-70, and Asp-71 on the DQ4 beta chain) could also
      contribute to the TrJ6 epitope because TrJ6 reacted stronger with DQ4- than with
      DQ5-bearing cell lines.

PMID- 7513682
TI  - FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium
      violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and
      biological properties, and antitumor activity.
AB  - A novel antitumor bicyclic depsipeptide, FR901228, was isolated from a broth
      culture of Chromobacterium violaceum No. 968 as colorless prisms and the
      molecular formula was determined as C24H36N4O6S2. This antibiotic reverted the
      transformed morphology of a Ha-ras transformant to normal, and exhibited
      prominent antitumor activities against murine and human tumor cell lines both in
      vitro and in vivo.

PMID- 7513683
TI  - Tetrodecamycin, a new antimicrobial antibiotic from Streptomyces.

PMID- 7513684
TI  - Histamine and exercise-induced hypoxemia in highly trained athletes.
AB  - To determine whether exercise-induced hypoxemia in extreme athletes results from
      an increase in histamine level during maximal incremental exercise, seven young
      athletes [YA; age 22.2 +/- 1.23 (SE) yr] and seven master athletes (MA; age 66.2
      +/- 2.94 yr), all of whom were known to develop exercise-induced hypoxemia, were
      compared with age-matched control groups (young controls and older controls,
      respectively). During maximal incremental exercise, blood samples for arterial
      blood gas analysis and for plasma and total histamine were drawn at rest and at
      50, 75, and 100% of maximal O2 uptake. The percentage of histamine released (%H)
      was calculated from plasma and total histamine samples. In all athletes (MA and
      YA groups), exercise induced an increase in %H with a concomitant decrease in
      arterial PO2 (PaO2); in control groups there was no change in either histamine
      levels or PaO2. When the data for the YA and MA groups were combined, a
      correlation was observed between the increase in %H and the drop in PaO2.
      Nevertheless, further studies are required to establish whether histamine plays a
      causative role in hypoxemia or is a response to injury.

PMID- 7513686
TI  - Permeability of parietal pleura to liquid and proteins.
AB  - The permselectivity of the parietal pleura was determined in spontaneously
      breathing anesthetized rabbits and dogs. In rabbits, we injected intrapleurally 5
      ml of 1-g/dl albumin solution containing 100 microCi of 131I-labeled albumin plus
      100 microCi of either lactate dehydrogenase (LDH) or alpha 2-125I-macroglobulin.
      Dogs received 100 ml of 1-g/dl albumin solution containing 100 microCi of 131I
      albumin plus 100 microCi of alpha 2-125I-macroglobulin. A transpleural pressure
      gradient was set, lowering the intracapsular pressure to -30 cmH2O. The solvent
      drag reflection coefficients (sigma f) were calculated as the ratio between
      tracer concentrations in capsular and pleural liquid collected at 60-180 min. In
      rabbits sigma f was 0.44 +/- 0.2 (SD) for albumin, 0.84 +/- 0.1 for LDH, and 0.93
      +/- 0.05 for alpha 2-macroglobulin. In dogs sigma f was 0.30 +/- 0.19 for albumin
      and 0.53 +/- 0.15 for alpha 2-macroglobulin. The hydraulic conductivity of the
      parietal pleura was 2.18 +/- 1.54 microliters.h-1.cmH2O-1.cm-2 in rabbits and
      1.22 +/- 1.13 microliters.h-1.cmH2O-1.cm-2 in dogs. The parietal pleura could be
      modeled by two pore populations with radii of 83-89 and 156-222 A. The
      permeability coefficient averaged 0.08-0.21 x 10(-6) cm/s for albumin, 0.06-0.09
      x 10(-6) cm/s for LDH, and 0.01-0.03 x 10(-6) cm/s for alpha 2-macroglobulin.

PMID- 7513685
TI  - PMN adherence to cat ischemic-reperfused mesenteric vascular endothelium under
      flow: role of P-selectin.
AB  - We studied polymorphonuclear leukocyte (PMN) adherence to cat ischemic-reperfused
      mesenteric artery and vein endothelia under conditions of flow in vitro. Under
      physiological shear rates, only a few PMNs adhered to non-ischemic-reperfused
      arterial and venous endothelia (11 +/- 2 and 20 +/- 3 PMN/mm2, respectively).
      However, after 60 min of ischemia and 20 or 120 min of reperfusion, a significant
      increase in PMN adherence to arterial endothelium was observed. At 20 min of
      reperfusion, 44 +/- 4 PMN/mm2 adhered, and at 120 min postreperfusion, 63 +/- 12
      PMN/mm2 adhered (P < 0.01 from control). Moreover, a greater degree of PMN
      adherence occurred on the venous than on the arterial endothelium. Thus, 159 +/-
      10 and 198 +/- 12 PMN/mm2 adhered to mesenteric venous endothelium isolated after
      20 and 120 min reperfusion, respectively (P < 0.01 vs. arteries). Furthermore,
      addition of PB 1.3 (20 micrograms/ml), a monoclonal antibody against P-selectin,
      5 min before perfusion with PMNs significantly attenuated the increase in PMN
      adherence to both arterial and venous endothelia (P < 0.01). These results
      indicate that PMN-endothelial interaction also occurs in conduit vessels after
      ischemia and reperfusion, although a more profound PMN adherence occurs in veins.

PMID- 7513687
TI  - Increased endothelium-derived NO in hypertensive pulmonary circulation of
      chronically hypoxic rats.
AB  - The hypothesis that the endothelium-derived relaxing factor/nitric oxide (EDNO)
      activity is elevated in chronic hypoxic pulmonary hypertension (CH-PHT) was
      tested using isolated Krebs-albumin-perfused rat lungs. Concentration of the EDNO
      decomposition products (NOx) in the lungs' effluent was measured by a modified
      chemiluminescence assay. The functional significance of basal EDNO production was
      studied by measuring the vasoconstrictor response to an EDNO synthesis inhibitor,
      N omega-nitro-L-arginine methyl ester (L-NAME). Reactivity to the endothelium
      dependent vasodilator substance P and to exogenous NO was also studied. More NOx
      was found in effluent from CH-PHT (22.3 +/- 9.8 nM) than control (0.4 +/- 3.9 nM)
      lungs. The L-NAME-induced vasoconstriction was greater in CH-PHT than in control
      rats. The sensitivity, but not the maximal vasodilation, to exogenous NO was
      elevated in CH-PHT. The substance P-induced vasodilation was potentiated in CH
      PHT compared with control rats and blocked by L-NAME in both groups. We conclude
      that basal and agonist-stimulated pulmonary EDNO activity is enhanced in this
      model of CH-PHT. The EDNO synthesis may play a counterregulatory role in CH-PHT.

PMID- 7513688
TI  - Heterogeneity between intracellular Ca2+ stores as the underlying principle of
      quantal Ca2+ release by inositol 1,4,5-trisphosphate in permeabilized pancreatic
      acinar cells.
AB  - Permeabilized rabbit pancreatic acinar cells were used to study the effects of
      Ca2+ pump inhibition and Ca2+ store depletion on the sensitivity of internal Ca2+
      stores to emptying by inositol 1,4,5-trisphosphate (Ins-1,4,5-P3). Complete
      inhibition of pump activity by thapsigargin resulted in the monoexponential loss
      of 92% of the actively stored Ca2+ with a half-time of 6.2 min. Under these
      conditions, Ca2+ release evoked by a submaximal concentration of Ins-1,4,5-P3 did
      not cease after 1.5 min, as was observed in the absence of thapsigargin, but
      continued for at least 5 min. This observation suggests that under normal
      conditions of Ca2+ pumping, a substantial part of the internal Ca2+ stores is not
      depleted by the action of Ins-1,4,5-P3 due to compensatory Ca2+ uptake. Evidence
      in support of the idea of compensatory Ca2+ pumping was obtained in exchange
      experiments performed in the absence of thapsigargin. The slow kinetics of
      sustained Ca2+ release in the absence of Ca2+ pump activity suggests that Ca2+ is
      released from stores containing either relatively few or less sensitive Ins-1,4,5
      P3-operated Ca2+ release channels. Gradual emptying of the internal Ca2+ stores
      by thapsigargin did not affect the potency with which Ins-1,4,5-P3 released Ca2+,
      indicating that the intravesicular Ca2+ content does not control the sensitivity
      of the Ins-1,4,5-P3-operated Ca2+ channel to activation by Ins-1,4,5-P3. This was
      confirmed using ruthenium red, which preferentially depleted the Ins-1,4,5-P3
      releasable store without affecting the EC50 for Ins-1,4,5-P3-stimulated Ca2+
      release. The data presented indicate that the quantal type of Ca2+ release
      observed with Ins-1,4,5-P3 requires compensatory Ca2+ pumping. Moreover, they
      support the idea that internal Ca2+ stores display differential sensitivities
      toward Ins-1,4,5-P3 rather than responding uniformly to this internal Ca(2+)
      mobilizing messenger.

PMID- 7513690
TI  - Helix sense of gramicidin channels as a "nonlocal" function of the primary
      sequence.
AB  - Gramicidin A (gA) channels are dimers formed by right-handed beta 6.3-helical
      monomers. The stereochemical basis for the preference of a right-handed
      conformation remains obscure, but it has earlier been demonstrated that the
      handedness can be shifted by changing the chirality of each residue in the LD
      sequence and therefore is determined by the peptide itself and not by channel
      membrane interactions. We now examine the contributions of Trp15, the central Val
      residues 6-8, and residues 1-5. None of these alone are sufficient to specify the
      helix sense. To examine the D-Val6-L-Val7-D-Val8 sequence, the register of the 3
      valines was shifted by one to L-Val5-D-Val6-L-Val7. The resulting analogue,
      [Val5,D-Ala8]gA, forms channels with a conductance and duration that are both
      somewhat less than those of gA channels. The reduced channel duration can be
      attributed to a steric conflict between the side chains of Val1 in one monomer
      and Val5 in the other monomer. The helix handedness is not altered by this
      modification, as shown by circular dichroism and two-dimensional nuclear magnetic
      resonance spectroscopy and by hybrid channel experiments. [Val5,D-Ala8]gA forms
      hybrid channels with gA (which forms right-handed channels), but not with des
      Val1-gA- (which forms left-handed channels). Similar hybrid channel analysis
      shows that des-Trp15-gA and [L-Ala1,D-Ala2,L-Ala3,D-Ala4]gA also form right
      handed channels. We conclude that the helix handedness most probably is a complex
      function of the arrangement of both the D-Val-L-Val-D-Val and the L-Trp-(D-Leu-L
      Trp)3 segments.

PMID- 7513689
TI  - Evidence for a second alpha 2-macroglobulin receptor.
AB  - alpha 2-Macroglobulin (alpha 2M)-methylamine binds to purified low density
      lipoprotein receptor-related protein (LRP), and it is assumed that LRP functions
      as the alpha 2M receptor in vivo. Binding of alpha 2M-methylamine to macrophage
      receptors elevates intracellular calcium ([Ca2+]i), inositol phosphates, and
      cyclic AMP. We have employed human alpha 2M-methylamine and recombinant receptor
      binding fragment (RBF) to study transduction mechanisms. Macrophages exposed to
      either ligand demonstrated a rapid rise in [Ca2+]i. Since the 39-kDa LRP/alpha 2M
      receptor-associated protein (RAP) blocks alpha 2M binding to LRP, we explored the
      effects of RAP upon signaling. Pretreatment of macrophages with RAP did not block
      the increase in [Ca2+]i elicited by alpha 2M-methylamine or RBF, suggesting a
      distinct binding site. RBF also elicited a transient 1.5-2.0-fold increase in
      inositol 1,4,5-triphosphate. In permeabilized macrophages, GTP gamma S and Gp
      p(NH)p potentiated and sustained this inositol 1,4,5-triphosphate increase.
      Preincubation of permeabilized macrophages with GDP beta S abrogated the effects
      of GTP gamma S. Our results suggest that the signaling alpha 2M receptor is
      coupled to a pertussis toxin-insensitive G protein and possibly to a cholera
      toxin-sensitive G protein. We conclude that macrophages contain a second alpha 2M
      receptor that is G protein-coupled.

PMID- 7513691
TI  - Glutamate receptors induce a burst of superoxide via activation of nitric oxide
      synthase in arginine-depleted neurons.
AB  - We have previously shown in cultured cerebellar granule neurons (Lafon-Cazal, M.,
      Pietri, S., Culcasi, M., and Bockaert, J. (1993) Nature 364, 535-537) that upon N
      methyl-D-aspartate stimulation, a nitric oxide synthase (NOS)-independent,
      arachidonic acid-dependent generation of superoxide free radicals (O2-.) is
      observed after a lag time of 10-15 min. Using the electron spin resonance spin
      trapping technique, we show that N-methyl-D-aspartate stimulation produced a more
      rapid burst of O2-. in L-arginine (L-Arg)-depleted neurons. These O2-. radicals
      are synthesized by NOS. KCl and kainate, which also stimulated NOS in these
      neurons, produced this rapid burst of O2-., which was blocked as follows: (a) in
      the presence of L-NG-nitro-arginine (L-Narg), and (b) by L-Arg repletion. This
      burst of O2-. was arachidonic acid-independent, and its time course was similar
      to that of nitric oxide production. It was also responsible for a weak but
      significant cell death that was suppressed by L-Narg and L-Arg.

PMID- 7513692
TI  - Depletion of intracellular Ca2+ stores activates nitric-oxide synthase to
      generate cGMP and regulate Ca2+ influx.
AB  - The mechanism of activation of the agonist-stimulated Ca2+ entry pathway in the
      plasma membrane is not known. To determine the role of nitric-oxide synthase
      (NOS) and cGMP in the regulation of this pathway, we used intact and streptolysin
      O (SLO)-permeable pancreatic acini and measured the relationship between Ca2+
      release from internal stores, the NO metabolic pathway, generation of cGMP, and
      activation of Ca2+ entry. We found that agonist- or thapsigargin (Tg)-activated
      Ca2+ entry is inhibited by L-NA, a specific inhibitor of NOS, and by LY83583, an
      inhibitor of guanylyl cyclase. Inhibition of Ca2+ entry by inhibition of NOS was
      reversed by the NO releasing molecules NO2- and sodium nitroprusside (SNP) and by
      Bt2cGMP. Inhibition of Ca2+ entry by inhibition of guanylyl cyclase was reversed
      by Bt2cGMP, but not by the NO releasing agents. The use of L-NA-treated cells and
      different concentrations of SNP revealed that cGMP has a dual effect on Ca2+
      entry. Increasing cGMP up to 10-fold above control activated Ca2+ entry. Further
      increase in cGMP up to 80-fold above control inhibited Ca2+ entry in a
      concentration-dependent manner. Measurement of cellular cGMP in intact cells
      showed that carbachol, Tg, and NO2- increased cGMP to similar levels. The effects
      of carbachol and Tg were inhibited by L-NA and LY83586, whereas the effect of NO2
      was inhibited only by LY83583. SLO-permeabilized cells were shown to be agonist
      competent in that the agonist induced Ca2+ release from the inositol 1,4,5
      trisphosphate (IP3) pool and activated a NO-dependent generation of cGMP. These
      cells were used to study the regulation of NOS by Ca2+ and by Ca2+ content of the
      internal stores. When internal stores were maintained loaded with Ca2+,
      increasing medium [Ca2+] up to 2.5 microM only modestly increased NOS activity.
      In contrast, the depletion of Ca2+ from internal stores markedly increased NOS
      activity independent of medium [Ca2+]. Thus, NOS senses both cytosolic [Ca2+]i
      and internal store Ca2+ load. We propose that activation of Ca2+ entry involves
      an agonist-mediated Ca2+ release from internal stores which activates a cellular
      pool of NOS to generate cGMP, which then modulates Ca2+ entry pathway in the
      plasma membrane. This mechanism can explain the capacitative nature of Ca2+
      entry. The biphasic effect of cGMP provides the cells with a negative feedback
      mechanism which inhibits Ca2+ entry during periods of high cell [Ca2+]i. This
      could allow oscillatory behavior of Ca2+ entry.

PMID- 7513693
TI  - A new member of the third class in the protein kinase C family, PKC lambda,
      expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line
      and also in many tissues and cells.
AB  - Protein kinase C (PKC)-related cDNA clones isolated from cDNA libraries of mouse
      P19 embryonal carcinoma cells and mouse brain encoded a 67-kDa protein, PKC
      lambda. PKC lambda shows the highest amino acid sequence identity with PKC zeta
      (72%), the third class of the PKC family. Northern blot analysis showed that the
      mRNA for PKC lambda is expressed in a wide variety of cells and tissues,
      including P19 and NIH 3T3 cells, as well as brain, kidney, testis, and ovary. In
      undifferentiated P19 cells, the mRNA for PKC lambda is the most abundant among
      all the PKC family members. The differentiation of P19 cells results in an
      increase in PKC alpha and epsilon, and a decrease in PKC lambda. Antiserum raised
      against a peptide of PKC lambda identified a 74-kDa protein in P19 cell extracts
      as well as in extracts from COS cells transfected with the PKC lambda expression
      plasmid. Autophosphorylation of the PKC lambda that immunoprecipitated with the
      specific antiserum was observed, indicating that PKC lambda possesses protein
      kinase activity. A phorbol ester binding assay using intact COS cells expressing
      PKC lambda failed to detect binding activity specific to PKC lambda at phorbol
      dibutylate concentrations up to 300 nM, suggesting that PKC lambda does not
      possess phorbol ester binding activity. These results, in conjunction with the
      results obtained in parallel experiments with PKC zeta and other PKC members,
      suggest a biochemical similarity between PKC lambda and zeta and their clear
      difference from other PKC members.

PMID- 7513694
TI  - Role of endogenous interferon-beta in lipopolysaccharide-triggered activation of
      the inducible nitric-oxide synthase gene in a mouse macrophage cell line, J774.
AB  - The role of endogenous tumor necrosis factor alpha (TNF-alpha) and interferon
      beta (IFN-beta) in lipopolysaccharide (LPS)-induced activation of the inducible
      nitric-oxide synthase (i-NOS) gene was investigated. By Northern analysis or
      reverse-transcription polymerase chain reaction, the mouse macrophage cell line 
      (J774) was found to respond to LPS treatment by increased expression of mRNAs
      specific for TNF-alpha, IFN-beta, and i-NOS with the kinetics unique for each
      gene. Bioassay of the culture supernatants showed that TNF-alpha and IFN-beta
      secreted by J774 cells increased from an undetectable level to about 300 and 340
      units/ml, respectively, 3-6 h after LPS stimulation. Nitrite concentration was
      found to increase from 0 to 7.8 and 28.5 microM by 12 and 24 h, respectively, in
      the culture supernatant of LPS-treated J774 cells. The presence of a neutralizing
      dose of antibodies against IFN-beta, but not against TNF-alpha, during treatment
      with either 10 ng or 1 microgram of LPS/ml significantly, but not completely
      decreased the level of i-NOS-specific mRNA expression and NO production. The
      incubation of J774 cells with mouse natural IFN-beta itself (up to the level of
      1,200 units/ml) did not induce i-NOS-specific mRNA and therefore did not
      stimulate J774 cells to produce NO. However, natural IFN-beta synergistically
      augmented the expression of i-NOS mRNA and the production of NO by J774 cells
      triggered by suboptimal concentrations of LPS (1 to 5 ng/ml). These data thus
      suggest that endogenous IFN-beta, but not TNF-alpha, produced by LPS-stimulated
      J774 cells specifically contributes, probably in an auto/paracrine fashion, to
      the activation of the i-NOS gene expression by LPS.

PMID- 7513695
TI  - Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the
      biogenesis of the cystic fibrosis transmembrane conductance regulator.
AB  - Deletion of phenylalanine at position 508 (delta F508) in the first nucleotide
      binding fold of the cystic fibrosis transmembrane conductance regulator (CFTR) is
      the most common mutation in patients with cystic fibrosis. Although retaining
      functional Cl- channel activity, this mutant is recognized as abnormal by the
      cellular "quality control" machinery and is retained within the endoplasmic
      reticulum (ER). We have used human epithelial cells and recombinant Chinese
      hamster ovary cells to identify molecular interactions that may contribute to
      this intracellular retention. Based upon coimmunoprecipitation and
      cosedimentation through glycerol density gradients, newly synthesized wild-type
      and delta F508 mutant CFTRs associated specifically with calnexin, the calcium
      binding transmembrane chaperone of the ER. This association was restricted to the
      immature (or ER-associated) forms of the CFTR proteins. Although the bulk of wild
      type and delta F508 CFTRs were present initially in complexes containing
      calnexin, only wild-type CFTR was able to escape from this association and exit
      the ER. Calnexin retains misfolded or incompletely assembled proteins in the ER
      and thus is likely to contribute to the mislocalization of mutant CFTR.

PMID- 7513696
TI  - Cloning and analysis of cDNA encoding a major airway glycoprotein, human
      tracheobronchial mucin (MUC5).
AB  - Two unique nucleotide probes for human tracheobronchial mucin glycoprotein (TBM)
      were generated via polymerase chain reaction with degenerate primers deduced from
      the TBM:TR-3A tryptic peptide sequence and were used to isolate a 3.6 kilobase
      cDNA, clone NP3a, from a human nasal polyp cDNA library. Clone NP3a was localized
      to chromosome 11 and contained a 3168 nucleotide open reading frame which encoded
      three TBM peptide fragments, thus confirming that clone NP3a partially encodes
      TBM. TBM also contains five tandem repeats of TTVGP/S and an octapeptide
      GQCGTCTN, which is conserved in human intestinal mucin MUC2 and rat intestinal
      mucin-like protein (MLP) suggesting that this sequence has a functional
      significance for secreted mucins. TBM has amino acid similarity to the cysteine
      rich domains at the carboxyl termini of MUC2, rat MLP, bovine and porcine
      submaxillary mucins, and human von Willebrand factor. Strikingly, a large
      percentage of the cysteine residues in the overlaps are highly conserved: 90% in
      MUC2 and von Willebrand factor, 80% of bovine submaxillary mucin, 70% in porcine
      submaxillary mucin, and 64% in rat MLP, suggesting that conserved cysteines may
      be important for the tertiary structure of secreted glycoproteins. These studies
      demonstrate that clone NP3a is a candidate for MUC5, making it the only human
      mucin gene reported to date whose gene product has been isolated from airway
      secretions.

PMID- 7513697
TI  - Binding specificity of T4 DNA polymerase to RNA.
AB  - Bacteriophage T4 DNA polymerase, product of phage gene 43 (gp43), is a
      multifunctional DNA-binding protein and a key component of the phage DNA
      replicase. It is also an RNA-binding protein that selectively recognizes a site
      on its mRNA (the translational operator) and represses its own translation. We
      examined the ability of the protein to discriminate between DNA and RNA by using
      a gel mobility shift assay with defined RNA and DNA substrates. A higher affinity
      to RNA as compared with DNA (about 100-fold) was observed in assays that utilized
      synthetic DNA and in vitro transcribed RNA substrates bearing the T4 gene 43
      translational operator sequence. The replacement of thymine with uracil in the
      synthetic DNA did not improve binding. The results suggest that the protein's
      selectivity for RNA is based in structure (intramolecular interactions) specific
      to the ribonucleotide sequence of the operator. Competition studies suggest that
      the protein determinants for RNA and DNA recognition are only partially
      overlapping.

PMID- 7513699
TI  - Bleomycin stimulates pro-alpha 1 (I) collagen promoter through transforming
      growth factor beta response element by intracellular and extracellular signaling.
AB  - The role of transforming growth factor beta as a mediator of the fibrogenic
      effect of bleomycin in lung has been investigated at the transcriptional level.
      Several constructs containing the rat pro-alpha 1 (I) collagen promoter fused to
      the chloramphenicol acetyltransferase gene were transfected into rat lung
      fibroblasts. Both bleomycin and transforming growth factor beta 1 increased
      promoter activity in fibroblasts transfected with constructs containing the
      transforming growth factor beta response element. Fibroblasts transfected with a
      deletion construct that lacks this response element did not respond to either
      bleomycin or transforming growth factor beta 1. Anti-transforming growth factor
      beta 1-neutralizing antibodies did not block the increase in promoter activity
      induced by bleomycin, suggesting intracellular signaling. Mutation of the
      transforming growth factor beta response element greatly reduced the bleomycin
      effect, which also infers intracellular signaling. In addition, plasmin added to
      the media greatly enhanced bleomycin stimulation of promoter activity
      demonstrating that transforming growth factor beta mediates the bleomycin effect
      through extracellular signaling.

PMID- 7513698
TI  - Inhibition of human immunodeficiency virus type 1 reverse transcriptase
      dimerization using synthetic peptides derived from the connection domain.
AB  - Based on presently available information on the structure of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase, peptides have been
      synthesized which correspond to the sequence of a particular region of the
      protein involved in formation of the active heterodimeric form of the enzyme.
      Several peptides that are 15-19 amino acids long and that are derived from the so
      called connection domain of the reverse transcriptase are able to inhibit
      dimerization of the enzyme and thus inhibit development of its enzymatic
      activities. In particular, a tryptophan-rich 19-mer corresponding to residues 389
      407 was relatively efficient, showing an apparent dissociation constant in the
      micromolar range for one or both of the subunits. The sequence of this region is
      identical for both subunits, since one (molecular mass of 51 kDa) is the
      proteolytic product of the other (molecular mass of 66 kDa). Dissociation of the
      preformed heterodimer could not be induced by the peptides, but increasing
      concentrations reduced the rate of dimerization in a concentration-dependent
      manner until it became immeasurable at high concentrations. The results suggest
      that inhibition of dimerization of reverse transcriptase is an attractive
      approach to chemotherapeutic intervention in HIV infection and that further
      development of peptide-based inhibition strategies is worth pursuing.

PMID- 7513700
TI  - Effect of the 39-kDa receptor-associated protein on the hepatic uptake and
      endocytosis of chylomicron remnants and low density lipoproteins in the rat.
AB  - The low density lipoprotein (LDL) receptor-related protein, which serves as the
      cell surface receptor for several proteins including alpha 2-macroglobulin
      protease complexes, has been proposed to be a candidate hepatocytic receptor for
      chylomicron remnants through its recognition of apolipoprotein E. We have studied
      the effect of two ligands for this receptor, activated alpha 2-macroglobulin and
      the recently described 39-kDa protein that copurifies with the LDL receptor
      related protein (receptor-associated protein), on the uptake and endocytosis of
      chylomicrons in intact rats and in isolated, perfused rat livers. Both of these
      ligands were rapidly taken up and endocytosed into the liver of rats.
      Chylomicrons from normal rats were injected in vivo and chylomicrons from
      estradiol-treated rats that were enriched in apolipoprotein E were added to liver
      perfusates. Prior administration of amounts of activated alpha 2-macroglobulin
      that saturated hepatic uptake mechanisms did not inhibit hepatic uptake or
      endocytosis of endogenously labeled cholesteryl esters of chylomicron particles
      in vivo or in perfused livers over a period of 15 min. By contrast, prior
      administration of saturating amounts of the receptor-associated protein
      (expressed in bacteria as a fusion protein with glutathione S-transferase)
      reduced hepatic uptake by about 30% and virtually abolished endocytosis. The
      receptor-associated protein inhibited hepatic uptake of human LDL in vivo by 70%
      and endocytosis by 81%. Our results show that receptor-associated protein
      sensitive processes predominate in the overall pathways by which chylomicron
      remnants are endocytosed by rat liver. Furthermore, they show that the receptor
      associated protein binds to and inhibits the function of the LDL receptor as well
      as the LDL receptor-related protein.

PMID- 7513701
TI  - Inhibitors of transcription such as 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole and isoquinoline sulfonamide derivatives (H-8 and H-7)
      promote dephosphorylation of the carboxyl-terminal domain of RNA polymerase II
      largest subunit.
AB  - The RNA polymerase IIO and IIA differ by the extent of phosphorylation in the
      carboxyl-terminal domain (CTD) of the largest subunit. It has been proposed that
      the IIA form of RNA polymerase II interacts with the promoter to form a stable
      preinitiation complex whereas the IIO form would be generated upon entry into
      initiation of transcription. Phosphorylation of the CTD might be required to
      release the interaction between the polymerase and the promoter binding factors.
      In this paper, we show that in the presence of actinomycin D, the phosphorylated
      IIO form accumulates. In contrast, the dephosphorylated IIA form accumulates
      while the amount of phosphorylated IIo form decreases in cells treated with CTD
      kinase inhibitors such as the nucleoside analog, 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole or the isoquinoline sulfonamide derivatives H-7* or H
      8. These changes are fast and suggest a very rapid phosphate turnover on the CTD.
      Transcription is inhibited in intact cells by drug concentrations that are
      effective in altering CTD phosphorylation, although no causal relationship is
      established yet. These effects do not concern other cellular functions such as
      protein synthesis. Thus isoquinoline sulfonamide derivatives might be helpful to
      further dissect the role of CTD phosphorylation in transcription.

PMID- 7513702
TI  - Basic peptides can be imported into yeast mitochondria by two distinct targeting
      pathways. Involvement of the peptide-sensitive channel of the outer membrane.
AB  - The interaction of several basic peptides with yeast mitochondria has been
      analyzed. The peptides were selected for their ability to block a cationic
      channel of the outer membrane, the peptide-sensitive channel. These peptides
      possess common characteristics, such as a net positive charge superior to 2 and
      the capacity to form amphiphilic structures. They can be divided into two classes
      as follows: peptides of class I derived from mitochondrial signal peptides, such
      as the presequence of cytochrome c oxidase subunit IV, e.g. pCyt OX IV (1-12) Y;
      and peptides of class II unrelated to the mitochondria, such as dynorphin B (1
      13). Class I peptides inhibited the translocation of a chimeric protein,
      cytochrome b2-DHFR, into the mitochondrial matrix, whereas peptides of class II
      failed to inhibit this import. Experiments with iodinated pCyt OX IV (1-12) Y and
      dynorphin B (1-13) showed, however, that both types of peptides were imported
      into yeast mitochondria in vitro and subsequently degraded. At 30 degrees C, two
      import mechanisms could be distinguished; the mitochondrial presequences (class
      I) were translocated into the matrix in a temperature- and potential-sensitive
      manner, probably along the general import pathway, while class II dynorphin B (1
      13) was imported into the intermembrane space by a process that was neither
      temperature- nor potential-sensitive. At 0 degree C, both peptides were imported
      in a class II manner. The class II characteristics suggested the existence of a
      direct pathway into the intermembrane space, which may be associated with the
      peptide-sensitive channel. This hypothesis is substantiated by the competition
      for the import into the mitochondria between peptides of the two classes. The
      import of pCyt OX (1-12) Y was inhibited at 30 degrees C only by peptides of
      class I, IV whereas, at 0 degree C, this import was also inhibited by peptides of
      class II. Import of peptides of the latter class was inhibited by peptides of the
      two classes both at 0 degree C and 30 degrees C.

PMID- 7513703
TI  - Activation of the SH2-containing protein tyrosine phosphatase, SH-PTP2, by
      phosphotyrosine-containing peptides derived from insulin receptor substrate-1.
AB  - The cytoplasmic insulin receptor substrate-1 (IRS-1), which is multiply
      phosphorylated in vivo on tyrosine residues, is a known binding protein for the
      tandem src homology 2 (SH2) domain-containing protein tyrosine phosphatase, SH
      PTP2. Eleven phosphotyrosyl (pY) peptides from IRS-1 were screened for allosteric
      activation of SH-PTP2 phosphatase activity toward phosphorylated, reduced,
      carboxyamidomethylated, and maleylated-lysozyme. Peptides IRS-1pY895, IRS
      1pY1172, and IRS-1pY1222 showed up to 50-fold acceleration of dephosphorylation.
      Analyses of Arg to Lys mutants in either or both SH2 domains indicate that both
      the N-terminal (N-SH2) and C-terminal (C-SH2) domains function in allosteric
      activation. Direct determination by surface plasmon resonance of the dissociation
      constants between pY peptides and glutathione S-transferase fusions to N-SH2 and
      C-SH2 domains reveals a 240-fold preference of the N-SH2 domain (compared with
      the C-SH2 domain) for IRS-1pY1172. The N-SH2 domain prefers IRS-1pY1172 > IRS
      1pY895 > IRS-1pY1222, whereas C-SH2 domain prefers IRS-1pY1222 > IRS-1pY895 > IRS
      1pY1172. These data suggest that each SH2 domain can bind to a distinct pY
      sequence of multiply phosphorylated protein substrates such as IRS-1, while
      activating hydrolysis at a third pY sequence bound in the SH-PTP2 active site. In
      addition, proteolysis and truncation studies reveal an autoregulatory function
      for the C-terminal region of SH-PTP2. Limited tryptic cleavage within the C
      terminus results in 27-fold activation of protein tyrosine phosphatase activity.
      The activated tryptic fragment cannot be further activated by pY peptide binding
      to the SH2 domains indicating that autoregulatory functions of the SH2 domains
      are dependent on the C-terminal region. These data suggest that multiple levels
      for control of SH-PTP2 enzymatic activity may exist in vitro and in vivo.

PMID- 7513704
TI  - Evidence for a functional role of Shc proteins in mitogenic signaling induced by
      insulin, insulin-like growth factor-1, and epidermal growth factor.
AB  - Shc proteins contain a single SH2 domain, lack catalytic activity, and are
      substrates for activated receptors for insulin, insulin-like growth factor-1 (IGF
      1), and epidermal growth factor (EGF). Treatment with these growth factors
      induced rapid tyrosine phosphorylation of Shc. We investigated the potential role
      of Shc in mitogenic signaling. Affinity-purified antibodies were microinjected
      into living Rat1 fibroblasts overexpressing human insulin receptors.
      Bromodeoxyuridine incorporation into newly synthesized DNA was subsequently
      studied to assess the importance of Shc. Cellular microinjection of anti-Shc
      antibody inhibited BrdU incorporation induced by insulin, IGF-1, and EGF, but did
      not affect cells stimulated by fetal calf serum. Microinjection of an oncogenic
      p21ras protein (T24) into quiescent cells produced constitutively active
      mitogenic signaling, and comicroinjection of T24 with the anti-Shc antibody
      restored insulin and EGF stimulation of DNA synthesis. Immunoprecipitates of Shc
      from lysates of insulin-stimulated cells removed 70-80% of guanine nucleotide
      releasing factor activity. These results indicate that Shc is an important
      component in a mitogenic signal transduction pathway that is shared by insulin,
      IGF-1, and EGF. The functional locus of Shc is either upstream of p21ras or lies
      on a distinct branch of the pathway leading to cell cycle progression.

PMID- 7513705
TI  - Intermediate filaments and disease: mutations that cripple cell strength.

PMID- 7513707
TI  - Cytokine-mediated protein kinase C activation is a signal for lineage
      determination in bipotential granulocyte macrophage colony-forming cells.
AB  - Granulocyte macrophage colony-forming cells (GM-CFC) have the potential to
      develop into either macrophages and/or neutrophils. With a highly enriched
      population of these cells we have found that although GM-CFC are equally
      responsive to macrophage colony stimulating factor (M-CSF) and stem cell factor
      (SCF) in terms of DNA synthesis, M-CSF stimulated the development of colonies
      containing macrophages in soft gel assays, while SCF promoted neutrophilic colony
      formation. When SCF and M-CSF were combined, mainly macrophage development was
      stimulated both in soft agar colony-forming assays and liquid cultures. An
      analysis of some potential signaling mechanisms associated with cytokine-mediated
      developmental decisions in GM-CFC revealed that M-CSF, but not SCF, was able to
      chronically stimulate phosphatidylcholine breakdown and diacylglycerol
      production, indicating that protein kinase C (PKC) may be involved in the action
      of M-CSF. Furthermore, M-CSF, but not SCF, can increase the levels of PKC alpha
      (PKC alpha) expression and stimulate the translocation of PKC alpha to the
      nucleus. When the PKC inhibitor, calphostin C, was added to GM-CFC cultured in M
      CSF then predominantly neutrophils were produced, conversely PKC activators added
      with SCF stimulated macrophage development. The data indicate a role for PKC in M
      CSF-stimulated macrophage development from GM-CFC.

PMID- 7513708
TI  - Staurosporine inhibits agrin-induced acetylcholine receptor phosphorylation and
      aggregation.
AB  - Agrin, a protein that mediates nerve-induced acetylcholine receptor (AChR)
      aggregation at developing neuromuscular junctions, has been shown to cause an
      increase in phosphorylation of the beta, gamma, and delta subunits of AChRs in
      cultured myotubes. As a step toward understanding the mechanism of agrin-induced
      AChR aggregation, we examined the effects of inhibitors of protein kinases on
      AChR aggregation and phosphorylation in chick myotubes in culture. Staurosporine,
      an antagonist of both protein serine and tyrosine kinases, blocked agrin-induced
      AChR aggregation in a dose-dependent manner; 50% inhibition occurred at
      approximately 2 nM. The extent of inhibition was independent of agrin
      concentration, suggesting an effect downstream of the interaction of agrin with
      its receptor. Staurosporine blocked agrin-induced phosphorylation of the AChR
      beta subunit, which occurs at least in part on tyrosine residues, but did not
      reduce phosphorylation of the gamma and delta subunits, which occurs on
      serine/threonine residues. Staurosporine also prevented the agrin-induced
      decrease in the rate at which AChRs are extracted from intact myotubes by mild
      detergents. H-7, an antagonist of protein serine kinases, inhibited agrin-induced
      phosphorylation of the gamma and delta subunits but did not block agrin-induced
      phosphorylation of the AChR beta subunit, AChR aggregation, or the decrease in
      AChR extractability. The results provide support for the hypothesis that tyrosine
      phosphorylation of the beta subunit plays a role in agrin-induced AChR
      aggregation.

PMID- 7513706
TI  - Distinct intracellular localization of Lck and Fyn protein tyrosine kinases in
      human T lymphocytes.
AB  - Two src family kinases, lck and fyn, participate in the activation of T
      lymphocytes. Both of these protein tyrosine kinases are thought to function via
      their interaction with cell surface receptors. Thus, lck is associated with CD4,
      CD8, and Thy-1, whereas fyn is associated with the T cell antigen receptor and
      Thy-1. In this study, the intracellular localization of these two protein
      tyrosine kinases in T cells was analyzed by immunofluorescence and confocal
      microscopy. Lck was present at the plasma membrane, consistent with its proposed
      role in transmembrane signalling, and was also associated with pericentrosomal
      vesicles which co-localized with the cation-independent mannose 6-phosphate
      receptor. Surprisingly, fyn was not detected at the plasma membrane in either
      Jurkat T cells or T lymphoblasts but was closely associated with the centrosome
      and to microtubule bundles radiating from the centrosome. In mitotic cells, fyn
      co-localized with the mitotic spindle and poles. The essentially non-overlapping
      intracellular distributions of lck and fyn suggest that these kinases may be
      accessible to distinct regulatory proteins and substrates and, therefore, may
      regulate different aspects of T cell activation. Anti-phosphotyrosine antibody
      staining at the plasma membrane increases dramatically after CD3 cross-linking of
      Jurkat T cells. The localization of lck to the plasma membrane suggests that it
      may participate in mediating this increase in tyrosine phosphorylation, rather
      than fyn. Furthermore, the distribution of fyn in mitotic cells raises the
      possibility that it functions at the M phase of the cell cycle.

PMID- 7513710
TI  - Strong increase in the tyrosine phosphorylation of actin upon inhibition of
      oxidative phosphorylation: correlation with reversible rearrangements in the
      actin skeleton of Dictyostelium cells.
AB  - When oxidative phosphorylation is inhibited in cells of Dictyostelium discoideum,
      the phosphorylation of tyrosine residues on actin is strongly increased. This
      increase is fully reversible. Under the same conditions the amoeboid cells
      undergo a series of shape changes. Within three minutes the pseudopods are
      withdrawn and replaced by cell surface blebs. Subsequently, the cells are
      rounding up to become immobile. In parallel with the changes in cell shape, the
      distribution of actin filaments is grossly altered within the cells. The cortical
      network of actin filaments of normal cells is broken down, and the F-actin forms
      large, irregular clusters deep within the cytoplasm. In these clusters the actin
      is associated with myosin II and with the heterodimeric F-actin capping protein
      cap32/34. After restoration of oxidative phosphorylation the actin returns within
      less than four minutes to its normal cortical position. A causal relationship
      between tyrosine phosphorylation and changes in the distribution of actin remains
      to be established. The rearrangements in the actin system that result from the
      inhibition of oxidative phosphorylation indicate that the organisation of this
      system and its maintenance in a functional state depend on the continuous supply
      of energy by ATP.

PMID- 7513712
TI  - Merosin is synthesized by thyroid cells in primary culture irrespective of
      cellular organization.
AB  - The in vitro synthesis and deposition of laminin family glycoproteins were
      studied using primary porcine thyroid cells cultured as monolayers or in
      follicles. The latter organization mimics the in vivo state of these polarized
      epithelial cells. In both cell systems a trimeric molecule was immunoprecipitated
      by using polyclonal antibodies against EHS-laminin. When the cells were fully
      polarized the protein was found at the basal pole of cells, irrespective of their
      organization. However, this molecule was different from laminin purified from a
      traditional source, the murine Engelbreth-Holm-Swarm (EHS) tumor. Thyroid cell
      laminin was composed of two light chains, analogous to EHS B1 and B2, and a
      disulfide-bonded heavy chain not found in EHS-laminin. The heavy chain was first
      synthesized as a 380 kDa polypeptide, then rapidly cleaved to a doublet of 350
      380 kDa, which was subsequently found in both cell extracts and conditioned
      culture media. This thyroid laminin variant was compared with merosin, another
      variant found in the basement membranes of trophoblast, Schwann cells, striated
      muscle and liver. The heavy chain (M) of merosin shows homology to EHS-laminin
      heavy chain at the C-terminal domain, and is usually found as two polypeptides of
      80 kDa and 300 kDa (Ehrig K., Leivo I., Argraves W. S., Ruoslahti E. and Engvall
      E. Proc. Nat. Acad. Sci. 87, 3264-3268, 1990). mRNA of the M chain was identified
      by RT-PCR in freshly isolated thyrocytes as well as in 6-day-old cultured thyroid
      cells. Furthermore, both the classical laminin heavy chain and the 350 kDa
      variant were detected by immunoblotting and immunofluorescence in the thyroid
      gland in vivo. All these results suggest strongly that merosin is a basement
      membrane component of thyroid cells in vivo and in vitro.

PMID- 7513709
TI  - The neuronal chondroitin sulfate proteoglycan neurocan binds to the neural cell
      adhesion molecules Ng-CAM/L1/NILE and N-CAM, and inhibits neuronal adhesion and
      neurite outgrowth.
AB  - We have previously shown that aggregation of microbeads coated with N-CAM and Ng
      CAM is inhibited by incubation with soluble neurocan, a chondroitin sulfate
      proteoglycan of brain, suggesting that neurocan binds to these cell adhesion
      molecules (Grumet, M., A. Flaccus, and R. U. Margolis. 1993. J. Cell Biol.
      120:815). To investigate these interactions more directly, we have tested binding
      of soluble 125I-neurocan to microwells coated with different glycoproteins.
      Neurocan bound at high levels to Ng-CAM and N-CAM, but little or no binding was
      detected to myelin-associated glycoprotein, EGF receptor, fibronectin, laminin,
      and collagen IV. The binding to Ng-CAM and N-CAM was saturable and in each case
      Scatchard plots indicated a high affinity binding site with a dissociation
      constant of approximately 1 nM. Binding was significantly reduced after treatment
      of neurocan with chondroitinase, and free chondroitin sulfate inhibited binding
      of neurocan to Ng-CAM and N-CAM. These results indicate a role for chondroitin
      sulfate in this process, although the core glycoprotein also has binding
      activity. The COOH-terminal half of neurocan was shown to have binding properties
      essentially identical to those of the full-length proteoglycan. To study the
      potential biological functions of neurocan, its effects on neuronal adhesion and
      neurite growth were analyzed. When neurons were incubated on dishes coated with
      different combinations of neurocan and Ng-CAM, neuronal adhesion and neurite
      extension were inhibited. Experiments using anti-Ng-CAM antibodies as a substrate
      also indicate that neurocan has a direct inhibitory effect on neuronal adhesion
      and neurite growth. Immunoperoxidase staining of tissue sections showed that
      neurocan, Ng-CAM, and N-CAM are all present at highest concentration in the
      molecular layer and fiber tracts of developing cerebellum. The overlapping
      localization in vivo, the molecular binding studies, and the striking effects on
      neuronal adhesion and neurite growth support the view that neurocan may modulate
      neuronal adhesion and neurite growth during development by binding to neural cell
      adhesion molecules.

PMID- 7513711
TI  - Cytoskeletal regulation of ion channel distribution in the tip-growing organism
      Saprolegnia ferax.
AB  - Growing hyphal tips of the oomycete Saprolegnia ferax possess a tip-high gradient
      of stretch-activated ion channels permeable to calcium. These mechanosensitive
      channels appear to play a direct role in the polarized tip growth process.
      Treatment of S. ferax hyphae with cytochalasin E leads to the disruption of
      plasmalemma-associated, peripheral cytoplasmic actin populations and altered
      morphology of apical protoplasts, and eliminates the tip-high gradient of stretch
      activated channels. Cytochalasin E did not alter the normal aggregation of
      stretch-activated channels. The density of spontaneous K+ channels was decreased
      in all regions of the hyphae after treatment with cytochalasin E. These results
      suggest that the peripheral F-actin network in the growing tip of S. ferax hyphae
      establishes or maintains the tip-high gradient of SA channels, either by the
      delivery of channel-bearing vesicles to the apex or by the interactions between
      the channels and the peripheral actin network.

PMID- 7513713
TI  - Differential induction of 'metabolic genes' after mitogen stimulation and during
      normal cell cycle progression.
AB  - Mitogenic stimulation of quiescent cells not only triggers the cell division
      cycle but also induces an increase in cell volume, associated with an activation
      of cellular metabolism. It is therefore likely that genes encoding enzymes and
      other proteins involved in energy metabolism and biosynthetic pathways represent
      a major class of mitogen-induced genes. In the present study, we investigated in
      the non-established human fibroblast line WI-38 the induction by mitogens of 17
      genes whose products play a role in different metabolic processes. We show that
      these genes fall into 4 different categories, i.e. non-induced genes, immediate
      early (IE) primary genes, delayed early (DE) secondary genes and late genes
      reaching peak levels in S-phase. In addition, we have analysed the regulation of
      these genes during normal cell cycle progression, using HL-60 cells separated by
      counterflow elutriation. A clear cell cycle regulation was seen with those genes
      that are induced in S-phase, i.e. thymidine kinase, thymidylate synthase and
      dihydrofolate reductase. In addition, two DE genes showed a cell cycle dependent
      expression. Ornithine decarboxylase mRNA increased around mid-G1, reaching
      maximum levels in S/G2, while hexokinase mRNA expression was highest in early G1.
      In contrast, the expression of other DE and IE genes did not fluctuate during the
      cell cycle, a result that was confirmed with elutriated WI-38 and serum
      stimulated HL-60 cells. These observations suggest that G0-->S and G1-->S
      transition are distinct processes, exhibiting characteristic programmes of gene
      regulation, and merging around S-phase entry.

PMID- 7513714
TI  - Immunodetection of chorionic gonadotropin and its subunits in human
      nonfunctioning pituitary adenomas.
AB  - Human nonfunctioning pituitary adenomas (NFPA) may produce CG in addition to the
      classical glycoprotein hormones (LH, FSH, and TSH). The aim of the present study
      was to localize LH beta, FSH beta, TSH beta, alpha-subunit (alpha SU), CG, and
      its beta-subunit (beta SU) in NFPA using a highly specific immunohistochemical
      technique. Nine NFPA, obtained at surgery, were processed for both electron
      microscopy and immunohistochemistry. Three tumors resulted oncocytomas, and six
      were null cell. Using an immunofluorescence technique, all tumors were positive
      for at least one glycoprotein; in particular, seven adenomas were markedly
      positive for CG beta, whereas only two were positive for the intact CG. No
      association among LH beta, FSH beta, and CG beta positivity could be demonstrated
      in the different adenomas. In the seven tumors positive for both CG beta and
      alpha SU, double fluorescence labeling demonstrated that six cases localized CG
      beta and alpha SU in different cells, but only one tumor showed the two subunits
      colocalized in the same cells. These data confirm that pituitary tumors
      synthesize both alpha SU and beta SU of glycoprotein hormones; in particular, the
      present study indicates that the majority of NFPA is able to synthesize CG,
      particularly its beta SU. Moreover, the localization of CG beta and alpha SU in
      different tumoral cells might account for the preferential expression of beta SU
      and alpha SU instead of the intact hormonal molecules in NFPA.

PMID- 7513716
TI  - Increased proteolysis of insulin-like growth factor-binding protein-3 (IGFBP-3)
      in noninsulin-dependent diabetes mellitus serum, with elevation of a 29
      kilodalton (kDa) glycosylated IGFBP-3 fragment contained in the approximately 130
      to 150-kDa ternary complex.
AB  - Insulin-like growth factor-I (IGF-I) in serum is predominantly bound in a ternary
      complex, consisting of IGF peptide, IGF-binding protein-3 (IGFBP-3), and an acid
      labile subunit, or a binary complex, consisting of IGF peptide and any of the six
      IGFBPs. In the binary complex, IGF-I is more bioavailable and has a faster
      turnover rate. Proteolysis of IGFBP-3 may alter the distribution of IGF-I between
      these complexes by reducing IGFBP-3 affinity for IGF-I and/or acid-labile subunit
      and may offer an additional mechanism for regulation of IGF availability. In the
      present study, sera from patients with noninsulin-dependent diabetes mellitus
      (NIDDM) were found to have significantly higher IGFBP-3 proteolytic activity than
      sera from age-matched healthy subjects (188 +/- 12% vs. 104 +/- 6% of a control
      serum pool; P < 0.001). The mean (+/- SE) of serum IGFBP-3 levels determined by
      Western ligand blotting was lower in NIDDM patients than in healthy control
      subjects (61.5 +/- 5% and 79 +/- 5% of a control serum pool, respectively; P <
      0.01). However, IGFBP-3 concentrations determined by RIA did not differ. This
      discrepancy could be explained by IGFBP-3 proteolysis, resulting in IGFBP-3
      fragments that are detectable by RIA, but not by Western ligand blotting. Western
      immunoblotting of sera with or without prior treatment with endoglycosidase-F
      demonstrated that a glycosylated 29-kilodalton (kDa) IGFBP-3 form with a protein
      core of 20 kDa was present in sera from healthy controls, and this fragment was
      increased in NIDDM and term pregnancy sera, suggesting that it is produced by
      endogenous proteolysis. The presence of the 29-kDa IGFBP-3 proteolytic fragment
      at about 130-150 kDa after neutral size chromatography of pooled sera may suggest
      that 29-kDa IGFBP-3 participates in ternary complex formation. Further studies
      are required to determine whether the avidity of ternary complex formation with
      the 29-kDa IGFBP-3 fragment is reduced and whether the resulting increased IGF
      turnover can explain the reduced IGF-I levels (z scores) observed in NIDDM
      patients compared to healthy subjects (-0.81 +/- 0.32 SD vs. +0.26 +/- 0.17 SD; P
      < 0.001). Neutral size-chromatography of sera demonstrated that IGFBP-3 protease
      activity in the approximately 130- to 150-kDa mol wt range is regulated by NIDDM
      and pregnancy in parallel with that of unfractionated sera.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7513717
TI  - Serum levels of prostate-specific antigen in normal boys throughout puberty.
AB  - Serum levels of prostate-specific antigen (PSA) were measured in a group of 132
      normal boys distributed in stages 1-5 of puberty. A highly sensitive (0.005
      ng/mL) immunofluorometric assay was developed and used in the study. PSA levels
      were generally undetectable in state I and rose sharply from stage II to III and
      from stage III to IV. A significant positive correlation was found between PSA
      and testosterone levels, PSA and LH levels, PSA and age, PSA and testicular
      volume, as well as PSA and pubertal stage. Our findings indicate that PSA levels
      measured with highly sensitive assays can be of utility in the hormonal
      evaluation of puberty in boys.

PMID- 7513715
TI  - Autoantibody epitope mapping of the 21-hydroxylase antigen in autoimmune
      Addison's disease.
AB  - Patients with idiopathic Addison's disease are characterized by cytoplasmic
      adrenal autoantibodies, detectable by indirect immunofluorescence of cryocut
      sections of human adrenal cortex. Recently, autoantibodies that bind a 55
      kilodalton protein in the microsomal fraction of adrenal gland extracts
      identified to be the cytochrome P450 enzyme 21-hydroxylase have been found in
      Addisonian patient sera. We confirm the finding and report here the autoantigenic
      epitopes involved in the autoantibody reactivity using recombinant DNA
      technology. Six cDNA fragments spanning different regions of the 21-hydroxylase
      gene were expressed as fusion proteins with glutathione S-transferase in
      Escherichia coli. Immunoblot analyses were used to evaluate the reactivity of the
      recombinant proteins with patients' sera to determine the autoepitopes involved.
      We found that a conserved region (amino acids 164-356) reacted with 25 of 30
      adrenal autoantibody-positive sera tested. One serum sample reacted only with the
      amino portion of the 21-hydroxylase (amino acids 1-162). In addition, 4 other
      enzymes important to steroid hormone biosynthesis, 11 beta-hydroxylase, 17 alpha
      hydroxylase, side-chain cleavage enzyme P450, and 3 beta-hydroxysteroid
      dehydrogenase, were expressed in E. coli, but none of them gave positive
      autoantibody reactions by Western blot assays, even using sera from 5 patients
      with type I autoimmune polyglandular syndrome. The availability of recombinant
      antigens has permitted structural analysis of the autoepitopes involved in the
      autoimmune response to 21-hydroxylase in Addison's disease. Our findings should
      lead to the development of a simple and specific tool for immunodiagnosis of the
      disease.

PMID- 7513718
TI  - Effects of growth hormone (GH) administration on functional hepatic nitrogen
      clearance: studies in normal subjects and GH-deficient patients.
AB  - A decline in serum urea levels and urinary urea excretion is usually seen after
      GH administration in humans, indicating overall protein anabolism. Whether this
      reflects the diminished supply of alpha-amino acids for urea synthesis or a
      substrate-independent hepatic mechanism is unknown. To pursue this we measured
      the urea nitrogen synthesis rate (UNSR) and blood alanine levels before, during,
      and after a 4-h constant iv infusion of alanine (2 mmol/kg BW.h). UNSR was
      estimated hourly as urinary excretion corrected for gut hydrolysis and
      accumulation in total body water. The slope of the linear relationship between
      UNSR and circulating alanine levels represents the hepatic components of
      conversion of amino nitrogen and is denoted the functional hepatic nitrogen
      clearance (FHNC). Eight male volunteers were randomly investigated on three
      occasions: 1) after 12-h iv saline infusion, 2) after 12-h iv GH infusion (1
      IU/h), and 3) after 2-day sc GH treatment (8 IU/day), followed by 12-h iv
      infusion of GH (1 IU/h). The UNSR (millimoles per h) during alanine infusion was
      significantly lower when the subjects were receiving GH therapy [maximum +/- SE,
      133.0 +/- 6.9 (saline) vs. 96.7 +/- 11.1 (12-h GH; P < 0.01) vs. 106.5 +/- 7.5 (2
      day GH; P < 0.05)]. FHNC (liters per h) was similar in all three studies [30.3 +/
      1.2 (saline) vs. 26.6 +/- 3.4 (12-h GH) vs. 27.0 +/- 2.6 (2-day GH)]. Six GH
      deficient adult patients were randomly studied twice: 1) on regular daily (at
      2000 h) sc GH therapy (3 IU/m2.day), and 2) after discontinuation of GH for 2
      days. The UNSR during alanine infusion was likewise significantly lower when the
      patients were receiving GH therapy [147.7 +/- 11.7 mmol/h (no GH) vs. 123.9 +/-
      9.1 mmol/h; P < 0.01]. FHNC (liters per h) values were similar in the two studies
      [29.2 +/- 3.8 (GH) vs. 27.5 +/- 4.5 (no GH)]. Our data confirm the anabolic
      action of GH and show that short term GH deprivation is associated with
      catabolism in terms of increased UNSR. The finding of unaltered FHNC suggests a
      GH-induced extrahepatic regulation of amino nitrogen conversion, rather than a
      substrate-independent hepatic mechanism.

PMID- 7513720
TI  - Plasma levels of bleomycin after intralesional injection.

PMID- 7513721
TI  - Laser-mediated transmural myocardial channels induce a hyalin degeneration of
      neighboring myocardium.

PMID- 7513719
TI  - Evidence for a GABAergic interface between cortical afferents and brainstem
      projection neurons in the rat central extended amygdala.
AB  - The synaptic circuitry of the intrinsic GABAergic system of the central extended
      amygdala (CEA) in relation to efferent neurons and cortical afferents was
      examined in the present study. Neurons in the CEA projecting to the dorsal vagal
      complex and the parabrachial complex were identified by the retrograde transport
      of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Postembedding GABA
      immunocytochemistry revealed that GABA-immunoreactive (GABA-IR) terminals formed
      largely symmetrical synaptic contacts with the perikarya and proximal dendritic
      processes of almost all WGA-HRP-labeled neurons in the CEA. To determine the
      relationship between cortical afferents and CEA GABAergic neurons, WGA-HRP was
      used to anterogradely label afferents from the insular cortex in combination with
      postembedding immunogold detection of GABA. Cortical afferents formed
      asymmetrical synaptic contacts predominantly on small dendrites and dendritic
      spines. Many of the dendrites postsynaptic to cortical terminals in the central
      nucleus were immunoreactive for GABA although only relatively few spines were
      GABA-IR. Combining pre-embedding GAD-immunocytochemistry with cortical lesions
      resulted in approximately 40% of degenerating terminals of insular cortical
      origin in the central nucleus in contact with small, GAD-IR dendrites and spines.
      The present results demonstrate that the neurons providing the major CEA outputs
      to the brainstem receive an extensive GABAergic innervation, strongly supporting
      our proposal that CEA efferent neurons are under strong tonic inhibition by
      intrinsic GABAergic neurons. Further, our finding that the major cortical input
      to the central nucleus preferentially innervates intrinsic GABAergic neurons
      suggests that these neurons in the CEA may serve as an interface between the
      principal inputs and outputs of this forebrain region.

PMID- 7513722
TI  - Constipation in the elderly.

PMID- 7513723
TI  - Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3
      CD4-CD8- thymocyte differentiation.
AB  - TCR-beta gene rearrangement or expression is necessary and sufficient for the
      progression of early alpha beta thymocyte differentiation from the CD3-CD4-CD8-
      triple negative (TN)3 to the CD4+CD8+ double positive stage. The onset of TCR
      beta rearrangement is currently thought to occur gradually. Some thymocytes were
      reported to be rearranged at the earliest (CD44+CD25-) TN stage, whereas other
      thymocytes did not initiate TCR-beta rearrangement until the latest (CD44-CD25-)
      TN stage. Here, we have isolated subsets of TN thymocytes on the basis of surface
      expression of CD44 and CD25, with c-kit as an additional marker. We present a
      revised model of early T cell development in which TCR-beta and TCR-gamma
      rearrangements occur abruptly, at the CD44lowCD25+ c-kitlowTN stage. A high level
      of c-kit expression defines pro-T cells which have not yet rearranged their TCR
      genes. Germ-line TCR-beta transcripts, and transcripts of recombination
      activating genes (RAG)-1 and 2, are detected before TCR-beta gene rearrangement.
      Analyses of TN thymocytes of RAG-1 mutant mice, and of various TCR mutant and TCR
      transgenic RAG-1 mutant mice, indicate the existence of a control point at the
      CD44-CD25+TN stage at which cells expressing a productively rearranged TCR-beta
      chain are selected for further differentiation.

PMID- 7513724
TI  - Signaling events during helper T cell-dependent B cell activation. I. Analysis of
      the signal transduction pathways triggered by activated helper T cell in resting
      B cells.
AB  - gp39 is expressed on anti-CD3-activated Th, and binds CD40 on the B cell, driving
      B cell cycle entry. In this study, the signal-transduction pathway initiated in B
      cells as a consequence of interacting with activated Th is examined. Unlike anti
      membrane Ig (anti-mlg) or anti-MHC class II, plasma membranes (PM) isolated from
      anti-CD3-activated Th, PMAct did not trigger an increase in the B cell
      intracellular concentrations of cAMP or calcium. In addition, PMAct did not
      stimulate protein kinase C activation as measured by myristoylated alanine-rich C
      kinase substrate (MARCKS) phosphorylation and protein kinase C translocation. The
      failure to detect these biochemical events may be caused by the asynchrony with
      which PMAct induce these normally transient biochemical changes. Alternatively,
      PMAct may not trigger these events. PMAct did induce the tyrosine phosphorylation
      of several B cell substrates. Neutralizing Abs directed against gp39 inhibited
      PMAct-induced protein tyrosine phosphorylation of B cell substrates. These
      results suggest that cognate interactions in B cells initiate a signal
      transduction pathway that is different from the pathway initiated by cross
      linking of mlg or MHC class II.

PMID- 7513725
TI  - An in vitro model for T cell-independent induction of humoral immunity. A
      requirement for NK cells.
AB  - We previously established an in vitro polyclonal model for membrane Ig-mediated
      Ig secretion by B cells in response to T cell-independent type 2 (TI-2) Ags, by
      using dextran-conjugated anti-IgD Abs (alpha delta-dex). We demonstrated that
      resting B cells activated with alpha delta-dex plus IL-2 secreted large amounts
      of Ig only in the presence of NK cells. In this report we show that, in contrast
      to small B cell-enriched spleen cells that require activation with the
      combination of alpha delta-dex and IL-2 for induction of Ig secretion, large B
      cells were induced to secrete Ig in response to alpha delta-dex, alone. These
      responses were inhibited by previous depletion of asialo-Gm-1+ cells from the B
      cell-enriched population, and restored both by the addition of freshly explanted
      NK cells and by in vitro-activated NK cells, suggesting a requirement for NK
      cells. Small alpha delta-dex-activated B cells could, however, also be stimulated
      to secrete Ig in the absence of added cytokines but only after the addition of in
      vitro-activated NK cells and not freshly explanted splenic NK cells. When highly
      purified large B cells, obtained by electronic cell sorting, were cultured with
      in vitro-activated NK cells, Ig secretion was induced even in the absence of any
      other added B cell stimulus. Because the splenic marginal zone has been
      implicated in humoral immune responses to TI-2 Ags, we further fractionated large
      B cells into marginal zone (MZB) and follicular (FB) B cells by electronic cell
      sorting. In vitro-activated NK cells stimulated large MZB, but not FB, cells to
      secrete Ig in the absence of exogenous stimuli. These data establish a T cell
      independent model for induction of Ig synthesis in the absence of any added
      cytokine and demonstrate a role for freshly explanted NK cells in stimulating Ab
      production in response to TI-2 Ags. Further, they show that pre-activated NK
      cells can induce Ig secretion from pre-activated B cells even in the absence of
      any added stimuli. These data also underscore a special role for the MZB cell in
      these responses.

PMID- 7513726
TI  - Molecular cloning and expression of early T cell costimulatory molecule-1 and its
      characterization as B7-2 molecule.
AB  - The interaction of T cell CD28/CTLA-4 receptors with B7-1 activation Ag on APC
      represents an important costimulatory pathway in T cell activation. However, it
      is now evident that this costimulatory pathway is neither unique nor universal
      for the activation of T cells. Our previous study indicated that a 60-kDa
      membrane protein, recognized by mAb 2D10, was expressed before B7 by activated
      murine B cells. This molecule was critically involved in activation of T cells in
      response to auto- and alloantigens. In the present study, we report on the
      isolation of a cDNA for this early T cell costimulatory molecule (ETC-1). ETC-1,
      like B7-1, is a member of the Ig supergene family and is composed of 303 amino
      acids. Nucleic acid sequence comparison indicated that ETC-1 is identical to the
      B7-2 molecule. When expressed in Chinese hamster ovary cells, ETC-1 showed
      profound T cell costimulatory activity as demonstrated by its ability to enhance
      CD4 T cell proliferation in response to Con A or anti-CD3 stimulation.
      Furthermore, ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. These
      results strongly support the notion that the interaction of ETC-1/B7-2 with CD28
      or CTLA-4 receptors represents an alternative T cell costimulatory pathway.

PMID- 7513727
TI  - Cytokine-activated endothelial cells internalize E-selectin into a lysosomal
      compartment of vesiculotubular shape. A tubulin-driven process.
AB  - The fate of E-selectin expressed on TNF-activated monolayers of HUVEC was
      investigated by confocal laser scanning microscopy. Cytokine-activated
      endothelial cells internalized mAb to E-selectin in a very rapid, energy
      dependent fashion. By contrast, mAb against ICAM-1 and VCAM-1 remained surface
      bound. The E-selectin mAb was recovered in intracellular compartments with a
      tubular morphology, some of which appeared to be interconnected. Cathepsin B, a
      ubiquitously expressed lysosomal protease, was found to co-localize in these
      structures. Functional specificity of E-selectin-internalization was observed
      upon addition of the fluorescent SLex-oligosaccharide to the activated HUVEC
      monolayers. Uptake into the same E-selectin-positive compartments was observed,
      whereas the control oligosaccharide Lex was not internalized at all. The process
      of internalization was found to be unaffected by most inhibitors of protein
      kinase C, cAMP-dependent PKA, or protein tyrosine kinase activity. Whereas
      cytochalasin B preincubation of HUVEC failed to inhibit the internalization
      process, colchicine and vinblastine, reagents that interfere with the metabolism
      of tubulin, prevented the formation of the elongated structures in which E
      selectin would normally be internalized. Concomitantly, the expression of E
      selectin at the cell surface was significantly increased.

PMID- 7513728
TI  - Lipopolysaccharide LPS-mediated soluble TNF receptor release and TNF receptor
      expression by monocytes. Role of CD14, LPS binding protein, and
      bactericidal/permeability-increasing protein.
AB  - Previously we demonstrated that two soluble(s) tumor necrosis factor receptors,
      TNF-R55 as well as sTNF-R75, are constitutively released in vitro by monocytes,
      and that this release was markedly enhanced after activation. Because LPS is an
      important activator of monocytes, we investigated the effect of LPS on sTNF-R
      release by monocytes. It was found that release of sTNF-R75, but not (or
      minimally) release of sTNF-R55, was enhanced after activation with LPS, reaching
      plateau levels after approximately 2 days. CD14, one of the membrane receptors
      for LPS, is an intermediate in this process, as shown in experiments using mAb
      directed against CD14. Under serum-free conditions, LPS-induced sTNF-R75 release
      was less as compared with release in the presence of serum, suggesting
      involvement of serum proteins. Addition of LPS binding protein (LBP) enhanced the
      LPS-induced sTNF-R75 release under serum-free conditions, but had no effect in
      the presence of serum. On the other hand, bactericidal/permeability-increasing
      protein (BPI), known to possess LPS neutralizing activity, inhibited LPS-induced
      sTNF-R75 release. Furthermore, cell surface expression of both types of TNF-R was
      shown to be controlled by LPS, LBP, and BPI. LPS caused, within 1 h, a complete
      reduction of TNF-R55 as well as TNF-R75 expression, followed by enhanced re
      expression of both receptors after 24 h. The down-modulation of expression was
      increased by LBP, whereas BPI counteracted the LPS-induced down-regulation. The
      LPS-enhanced release of sTNF-R75, capable of inactivation of TNF, as well as LPS
      induced initial down-modulation of TNF-R expression leading to postulated
      temporary unresponsiveness to TNF may share in a physiological mechanism to
      carefully control the effects of TNF.

PMID- 7513729
TI  - Nitric oxide involvement in tumor-induced immunosuppression.
AB  - The mechanisms of immunosuppression induced by colon cancer in rats were
      investigated at the systemic and tumor levels. During tumor growth (after i.p.
      injection of rat colon adenocarcinoma cells in syngeneic BD IX rats), Con A
      induced proliferation of splenic mononuclear cells decreased and nitric oxide
      (NO) production by splenic macrophages increased concomitantly. Incubating
      splenic mononuclear cells with an inhibitor of NO synthase, NG-monomethyl-L
      arginine, restored lymphocyte proliferation. A low level of inducible NO synthase
      mRNA was detectable in tumors by Northern blotting, with a weak increase during
      tumor growth. The NO concentration measured in the tumor nodules increased weakly
      parallel to the tumor growth. Five and six weeks after tumor cell injection,
      tumor-infiltrating lymphocytes from disaggregated tumors did not proliferate in
      the presence of Con A. Addition of NG-monomethyl-L-arginine inhibited the
      production of NO in tumor dissociations and enhanced tumor-infiltrating
      lymphocyte proliferation. Glyceryl trinitrate (a NO-releasing compound) totally
      inhibited the lymphocyte proliferation in vitro while it slightly reduced the
      tumor cell proliferation. T lymphocytes were therefore more sensitive to NO than
      were tumor cells. Culture medium from tumor cells induced NO production by
      splenic macrophages, although the factor involved has not yet been identified.
      Furthermore, tumor cells could also play a part in NO production by tumors
      because the tumor cells were induced to produce NO by IFN-gamma plus IL-1. These
      results strongly suggest the participation of NO in the tumor-induced
      immunosuppression in rats.

PMID- 7513730
TI  - Identification of CD7 glycoprotein as an accessory molecule in HIV-1-mediated
      syncytium formation and cellfree infection.
AB  - A major cytopathic effect seen upon in vitro infection of CD4+ human T cells by
      the HIV is cell-to-cell fusion that results in giant cell (or syncytium)
      formation. Membrane fusion is required for infection by cellfree virions and in
      syncytium formation. We report here that the human T cell surface molecule, CD7,
      is important for the HIV-1 fusion process. CD7 is a roughly 40-kDa glycoprotein
      member of the Ig supergene family that is expressed early in the ontogeny of
      thymocytes and on the majority of peripheral blood T cells, as well as on NK
      cells and a small subpopulation of B cells. Anti-CD7 mAbs inhibited HIV-1-induced
      cell-cell fusion and prevented cellfree infection of SupT1 cells. The
      antisyncytial activity of the CD7 Abs is not because of cross-reactivity with CD4
      or with viral proteins. Epitope mapping revealed at least two regions of the
      molecule that are important for preventing membrane fusion. Cells rendered CD7-
      are poorly infectable by cellfree virus. Additionally, cells rendered CD7- are
      more easily inhibited from fusing in syncytium formation assays. The collective
      results support a central role for human CD7 in the process of HIV infection.

PMID- 7513732
TI  - Residue-specific immunochemical sequence prediction.

PMID- 7513731
TI  - Production of monoclonal antibodies against epitopes of the main coat protein of
      filamentous fd phages.
AB  - Three monoclonal antibodies (MAbs) were produced which react with epitopes of the
      main structural coat protein (pVIII) of filamentous fd phages as demonstrated by
      solid-phase fluorometric enzyme immunoassays and by immunoelectron microscopy.
      The antibodies are of the IgG1, IgG2a and IgG2b immunoglobulin subclasses. Since
      they also react with recombinant phages expressing antigen fragments in their
      pIII region they may be suitable reagents for the demonstration and isolation of
      filamentous phages used in recombinant protein technology.

PMID- 7513734
TI  - Quantitation of endothelial cell specific protein E-9 employing a single
      monoclonal antibody in an indirect sandwich ELISA.
AB  - An indirect enzyme-linked immunosorbent assay is described for the quantitation
      of protein E-9 which is specifically expressed on human vascular endothelial
      cells. The assay capitalizes on the dimeric structure of the E-9 protein by
      utilizing a single monoclonal antibody as both the capture and detection reagent.
      Detection is achieved by conjugating the Mab with biotin and is followed by the
      addition of streptavidin peroxidase to provide high sensitivity. Bound activity
      is measured by enhanced chemiluminescence utilizing standard Amerlite chemistry.
      The optimised assay is reproducible and is highly sensitive. Using this assay it
      was possible to detect the presence of E-9 protein in tissue culture media of
      endothelial cells and in serum samples--in one case even at 1/100 dilution. In
      vitro, X irradiation resulted in a greater than two-fold increase (P < or =
      0.005) in the level of E-9 protein in culture supernatants of human umbilical
      vein endothelial cells (HUVEC). There are potential applications for measurements
      of E-9 protein in body fluids and tissue extracts from patients with a vast
      variety of diseases characterised by vascular endothelial damage and/or
      activation.

PMID- 7513735
TI  - Boc-Cys(Npys)-OH (BCNP): an appropriate reagent for the identification of T cell
      epitopes in cystine and/or cysteine-containing proteins.
AB  - Some T cell epitopes become inactive when their thiols are blocked with various
      irreversible reagents (Regnier-Vigouroux, 1988; Maillere, 1992; Maillere et al.,
      1993). Blocking protein and peptide thiols with BCNP (Boc-Cys(Npys)-OH)
      constitutes a most appropriate strategy when searching for thiol-containing T
      cell epitopes. Free cysteines can thus be readily transformed into disulphide
      like moieties which not only resist undesirable oxidative reactions but which
      also remain susceptible to reduction by antigen presenting cells, a prerequisite
      for the activity of thiol-dependent T cell epitopes. We describe the use of this
      reagent in a study of the intact disulphide-rich protein, toxin alpha from Naja
      nigricollis, and also two disulphide-containing toxin fragments.

PMID- 7513736
TI  - Abnormal keratin 1 and 10 cytoskeleton in cultured keratinocytes from
      epidermolytic hyperkeratosis caused by keratin 10 mutations.
AB  - Epidermolytic hyperkeratosis is caused by mutations of the differentiation
      specific keratins K1 and K10. These mutations produce a weakened cytoskeleton
      that is prone to collapse resulting in cell fragility and lysis. In this study we
      have analyzed cultured keratinocytes from EHK patients bearing 10R-to-H and 15L
      to-S mutations within the 1A segment of the K10 rod domain. Keratinocytes were
      grown submerged in serum-free medium and induced to differentiate by growing to
      confluence and increasing the Ca++ concentration in the medium. Cultures were
      either harvested for mRNA sequence analysis or subjected to immunofluorescence
      microscopy. Differentiating keratinocytes from these patients were found to
      express these K10 mutations in their mRNA. Moreover, these cells could be
      distinguished from normal keratinocytes by their aberrant morphology. EHK
      keratinocytes frequently exhibited a collapsed perinuclear network of K1/K10
      filaments and sometimes peripheral granules of K1 and K10 aggregates, reminiscent
      of the cells of the suprabasal layers in these patients. This report documents
      the expression of mutant keratin 10 in cultured EHK keratinocytes.

PMID- 7513733
TI  - A versatile synthetic peptide-based ELISA for identifying antibody epitopes.
AB  - A simple, versatile and very inexpensive procedure for cross-linking synthetic
      peptides to the polystyrene surfaces of micro-well assay plates for use in ELISA
      was developed. The method is based on the use of poly-L-lysine (PLL) as the
      anchor protein for synthetic peptides which were then easily and covalently
      linked to the PLL using glutaraldehyde. The synthetic peptides used for the study
      were based on the amino acid sequence of the equine infectious anemia virus
      (EIAV) envelope sequence and evaluated as antigens in an ELISA designed to detect
      antibodies in serum of EIAV-infected horses and ponies. The ELISA using cross
      linked peptides proved to be significantly more sensitive when compared to assays
      where passively coated peptides were used. In one instance, a peptide was
      identified that was not recognized by any of our antisera and appeared not to
      bind to the assay plates. However, once this peptide was cross-linked to the
      assay plate it proved to be very useful for detecting EIAV-specific antibodies.
      This cross-linking approach functioned equally well with peptides of various
      charges and sizes and did not appear to alter epitopes contained in the peptides.

PMID- 7513737
TI  - Epitope mapping for epidermolysis bullosa acquisita autoantibody by molecularly
      cloned cDNA for type VII collagen.
AB  - Epidermolysis bullosa acquisita is a subepidermal blistering disease in which
      patients have autoantibodies against the non-collagenous domain of type VII
      collagen. Starting with previously isolated 1-kilobase pair (Kb) cDNA for this
      autoantigen, we isolated overlapping cDNAs with a combined open reading frame of
      approximately 3.2 Kb, encoding most (approximately 115 kilodaltons [KDa]) of the
      N-terminal non-collagenous domain of type VII collagen. To localize immunogenic
      domains, we produced maltose-binding fusion proteins with cDNA encoding different
      portions of this autoantigen. These cDNA fragments scan from 5' to 3' of this non
      collagenous domain and overlap each other. An immunoblot analysis of these fusion
      proteins with eight epidermolysis bullosa acquisita patient sera demonstrated
      that each patient serum binds to different regions of this molecule and that
      epitopes for these patient sera locate throughout this autoantigen. These data
      suggest that multiple epitopes on the N-terminal non-collagenous domain of type
      VII collagen are recognized by circulating autoantibodies in patients with
      epidermolysis bullosa acquisita.

PMID- 7513739
TI  - Variation of differentiation in nail and bovine hoof cells.
AB  - Human nail plate contains two distinct types of keratins, skin-type and hair-type
      keratins. To elucidate that nature of the differentiation pathway of nail, we
      examined the expression of these keratins in human nail as well as in cultured
      cells taken from bovine hoof matrix. In this study we succeeded in showing that
      human nail matrix is characterized by the segregated localization of skin- and
      hair-type keratins except for the apical matrix in which both types of keratins
      are co-expressed. These results allow us to infer that some of the nail cells
      possibly divert the pattern of keratin expression during differentiation in vivo.
      Cultured cells taken from the ventral matrix of bovine hoof, which undergo the
      pathway of hair-type differentiation in vivo, expressed skin-type keratins
      together with hair-type keratins, thereby indicating that these cells develop
      into another pathway of differentiation (skin-type differentiation) from hair
      type differentiation developed in vivo. These results provide us with a further
      insight into nail differentiation under which nail cells develop into multiple
      patterns of differentiation in vivo and in vitro.

PMID- 7513738
TI  - Isolation and characterization of a novel hair follicle-specific gene, Hacl-1.
AB  - We have isolated a hair-follicle-specific gene, termed hacl-1, from a cDNA
      library of ICR mouse skin. Hacl-1 is expressed specifically in skin, and its mRNA
      level is correlated with the active state of hair follicles in developmental and
      regenerative processes of hair. Its mRNA is approximately 1 kilobase pairs (kb).
      Its cDNA was completely co-linear with the genomic clone, indicating that the
      hacl-1 gene is composed of one exon. The hacl-1 gene has an open reading frame of
      579 base pairs (bp). The deduced amino acid sequence showed six direct repeats of
      a decapeptide on the C-terminal side. The repetitive unit contains a CQP motif,
      which is present in repetitive peptide sequences of some hair- and epidermal-cell
      specific proteins. In situ hybridization with a 3' untranslated region of the
      hacl-1 cDNA as a probe showed that hacl-1 was expressed specifically in the
      keratogenous zone of the cortical cells of the hair shaft. No other components of
      hair follicles or epidermis showed a positive signal. Thus, hacl-1 is a novel,
      hair-follicle-specific gene.

PMID- 7513740
TI  - Expression of monoclonal antibody HECA-452-defined E-selectin ligands on
      Langerhans cells in normal and diseased skin.
AB  - The cutaneous lymphocyte-associated antigen recognized by the monoclonal antibody
      HECA-452 has been thought to play a major role in the homing of memory T-cell
      subsets to the skin by virtue of its ability to bind to E-selectin of dermal
      microvascular endothelial cells. Considering that the homing of different
      leukocyte populations to the skin may involve similar mechanisms, we studied the
      expression of HECA-452-reactive molecules on CD1a+ epidermal Langerhans cells.
      Immunofluorescence double-labeling of cryostat sections and epidermal sheets of
      normal skin revealed HECA-452 immunoreactivity on a subpopulation of dermal and
      epidermal CD1a+ cells, whereas upon flow-cytometric analysis of epidermal single
      cell suspensions virtually all CD1a+ cells bound HECA-452 antibodies. We observed
      a marked upregulation of HECA-452-antigen expression on CD1a+ epidermal cells and
      a pronounced increase in the number of HECA-452+/CD1a+ dermal cells in lesional
      skin from inflammatory and neoplastic lymphocytic skin diseases, compared to
      normal skin. The molecule detected by the HECA-452 antibody on Langerhans cells
      is neuraminidase sensitive and contains a CD15 (LewisX) carbohydrate backbone.
      Because Langerhans cells react with the sialyl-LewisX-specific antibody CSLEX1,
      it is very likely that the HECA-452-reactive structure is or contains sialyl
      LewisX. Our data are compatible with the view that i) resident epidermal
      Langerhans cells upregulate HECA-452-antigen expression due to the cytokine
      profile generated in the disease process or ii) that Langerhans cell precursors
      express HECA-452-antigens and show an enhanced immigration into lesional skin.
      The characterization of HECA-452+ cells in peripheral blood may not only clarify
      this issue but may also help to identify the still elusive Langerhans cell
      precursor.

PMID- 7513741
TI  - Complement peptides C3a- and C5a-induced mediator release from dissociated human
      skin mast cells.
AB  - The complement peptides C3a and C5a have been shown previously to release
      histamine from human basophils but not human lung mast cells. As skin mast cells
      differ from those of the lung in both immunocytochemical and functional
      properties, we examined the ability of these anaphylatoxins to release preformed
      and newly generated mediators from human dispersed skin mast cells. In
      concentration-response studies, both C3a and C5a released histamine in a
      concentration related manner with C5a being 40-50 times more potent. However, the
      extent of histamine, 15-20%, was considerably less than that released from
      basophils. This was not due to catabolism of the peptides by mast cell proteases,
      mast cell supernatants that contained C5a being effective in releasing basophil
      histamine. Removal of the C-terminal arginine from C3a and C5a abolished their
      activity on skin mast cells. In time-course studies, histamine release induced by
      C3a and C5a was complete within 15 seconds. Complement-induced histamine release
      is a non-cytotoxic process as evidenced by 2-deoxy-D-glucose and antimycin A,
      inhibitors of glycolysis and oxidative phosphorylation, respectively. In contrast
      to IgE-dependent stimulation, anaphylatoxin-induced histamine release from human
      skin mast cells is independent of extracellular calcium. Both C3a and C5a at
      concentrations that induced 10-16% net histamine release caused a negligible
      release of the newly generated mediator, PGD2. The results suggest that C3a and
      C5a stimulate human skin mast cells in a manner similar to substance P and
      related basic secretagogues. However, the activation site for C3a and C5a appears
      to be different to that for substance P as the substance P antagonist (D-Pro4, D
      Trp7,9,10) SP4-11 inhibited histamine release stimulated by substance P but not
      that induced by C3a and C5a.

PMID- 7513742
TI  - A keratin 14 mutational hot spot for epidermolysis bullosa simplex, Dowling
      Meara: implications for diagnosis.

PMID- 7513743
TI  - Replication of cucumber mosaic virus satellite RNA from negative-sense
      transcripts produced either in vitro or in transgenic plants.
AB  - Both positive [(+)] and negative [(-)] sense versions of two satellite RNA
      (satRNA) genes from cucumber mosaic virus (CMV), the necrogenic I17N and the
      nonnecrogenic R, have been introduced into the genome of tobacco plants. On
      infection with satRNA-free CMV, satRNA was amplified in plants expressing each of
      the four genes. All four genes confer protection against CMV infection. However,
      co-inoculation of plants with viral RNA and CMV satRNA transcripts synthesized in
      vitro showed that (-) sense transcripts were less active than the corresponding
      (+) sense transcripts. This is the first report that (-) sense CMV satRNA
      transcripts can serve as a template for satRNA replication.

PMID- 7513744
TI  - Differential host-dependent expression of alpha-galactosyl epitopes on viral
      glycoproteins: a study of eastern equine encephalitis virus as a model.
AB  - The carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (alpha-galactosyl) is
      abundantly expressed on cells of non-primate mammals, prosimians and New World
      monkeys, where it is synthesized by the enzyme alpha 1,3-galactosyltransferase
      (alpha 1,3GT). Old World monkeys, apes and humans lack alpha 1,3GT and hence do
      not synthesize alpha-galactosyl epitopes. Instead, these species produce a
      natural antibody, anti-Gal, which interacts specifically with alpha-galactosyl
      epitopes and which constitutes up to 1% of circulating immunoglobulins in humans.
      We have used eastern equine encephalitis (EEE) virus as a model to examine the
      differential expression of alpha-galactosyl epitopes on the glycoproteins of
      virus propagated in cells that either produce or lack alpha 1,3GT. As predicted,
      virus propagated in Vero cells (derived from the African green monkey, an Old
      World monkey) did not express alpha-galactosyl epitopes. In contrast, virus
      propagated in mouse 3T3 cells (EEE3T3) expressed approximately 80 alpha
      galactosyl epitopes per virion on both the E1 and the E2 envelope glycoproteins.
      Thus, expression of the alpha-galactosyl epitope on virions paralleled that on
      host cells. The binding of anti-Gal antibody to these epitopes on EEE3T3 virions
      partially neutralized virus infectivity, raising the possibility that anti-Gal
      production in hosts may influence the initial infectious stage of viruses
      expressing alpha-galactosyl epitopes.

PMID- 7513745
TI  - Interactions between drug resistance mutations in human immunodeficiency virus
      type 1 reverse transcriptase.

PMID- 7513746
TI  - Corticosteroid immunosuppression and monoclonal antibody-mediated CD5+ T
      lymphocyte depletion in normal and equine infectious anaemia virus-carrier
      horses.
AB  - The immune control of chronic equine infectious anaemia (EIA) lentiviral
      infection was investigated by specifically depleting CD5+ T lymphocytes in vivo
      with monoclonal antibody (MAb) or by immunosuppression with corticosteroids. MAb
      was given at 25 to 50 mg/day intravenously for 11 days. Murine IgG1 anti-equine
      CD2 MAb (n = 2 horses) or IgG1 (n = 2) and IgG2a control MAb (n = 2 normal; 2 EIA
      infected) did not deplete CD2+ T lymphocytes in horses. Horses given murine IgG2a
      anti-CD5 MAb HB19A (n = 4 normal; 5 EIA-infected) had depletion of peripheral
      blood CD5+ T lymphocytes during treatment. These horses, however, maintained a
      residual population of CD2+ T lymphocytes [15 (+/- 3)% of pretreatment numbers]
      that did not express CD5 but expressed either CD4 or CD8. These antigenically
      modulated CD5- T lymphocytes responded normally in vivo to intradermal
      inoculation with phytohaemagglutinin and in vitro to allogeneic leukocyte
      stimulation in one-way mixed lymphocyte reactions. EIA virus-infected horses (n =
      5) did not develop recrudescent viraemia or disease following in vivo CD5+ T
      lymphocyte depletion. Immunosuppression of EIA virus-infected horses with
      corticosteroids (1 mg/kg body weight/day, intravenously for 9 days) resulted in
      detectable recrudescent EIA viraemia in 6/11 horses (55%) and recrudescent
      disease in 9/11 horses (82%). Normal horses (n = 3) treated with corticosteroids
      developed no clinical disease. These results demonstrate that the use of murine
      IgG2a MAbs to appropriate equine lymphocyte antigens will facilitate in vivo
      investigation of the role of T lymphocyte subpopulations in the control of EIA or
      other important equine diseases.

PMID- 7513747
TI  - Swertifrancheside, an HIV-reverse transcriptase inhibitor and the first flavone
      xanthone dimer, from Swertia franchetiana.
AB  - The first flavone-xanthone C-glucoside, swertifrancheside, was isolated from
      Swertia franchetiana, and its structure was elucidated on the basis of
      spectroscopic analysis as 1,5,8-trihydroxy-3-methoxy-7-(5',7',3'',4''-
      tetrahydroxy-6'-C-beta-D-glucopyranosyl-4'-oxy-8'-flavyl)-xanthone . This
      compound was a moderately potent inhibitor of HIV reverse transcriptase.

PMID- 7513748
TI  - Antihypertensive activity of 6-O-galloyl-D-glucose, a phenolic glycoside from
      Sapium sebiferum.
AB  - The antihypertensive activity of a phenolic glycoside contained in the leaves of
      Sapium sebiferum was investigated. From intravenous screening using spontaneously
      hypertensive rats, 6-O-galloyl-D-glucose was identified as an active substance.
      The hypotensive action of this compound appears to be produced by an inhibition
      of noradrenaline release and/or a direct vasodilatation.

PMID- 7513749
TI  - CD44-hyaluronate interaction mediates in vitro lymphocyte binding to the white
      matter of the central nervous system.
AB  - The cell adhesion molecule CD44 is expressed in the central nervous system,
      especially on glial cells in the white matter, the extracellular matrix of which
      also contains one of its ligands, hyaluronate. We investigated the role of CD44
      and hyaluronate in the adhesion of human peripheral blood lymphocytes to
      myelinated areas of cerebellum by an in vitro binding assay. Hermes-1 epitope,
      which recognizes the hyaluronate binding site of CD44, and Hermes-3 epitope,
      involved in lymphocyte binding to mucosal high endothelial venules, were both
      immunohistochemically expressed in the white matter. No immunoreactivity was
      observed with mAb Var3.1, which sees variant forms of CD44 containing the exon v6
      encoding region. The molecular weight analysis showed that CD44 of the white
      matter was identical to the major 90 kD form of CD44 present on lymphocytes. The
      binding of both T and B lymphocytes was significantly inhibited by pretreatment
      of both cells and sections with mAb Hermes-1 but not with Hermes-3. Digestion of
      the sections and/or lymphocytes with hyaluronidase also reduced lymphocyte
      binding. These findings implicate that CD44-hyaluronate mediates lymphocyte
      adhesion to the white matter and this interaction may be involved in the
      pathogenesis of inflammations and lymphomas of the central nervous system.

PMID- 7513750
TI  - An ultrastructural study of NADPH-diaphorase and nitric oxide synthase in the
      perivascular nerves and vascular endothelium of the rat basilar artery.
AB  - This is the first report on the ultrastructural distribution of nicotinamide
      adenine dinucleotide phosphate-diaphorase activity and neuronal isoform (Type I)
      of nitric oxide synthase immunoreactivity in perivascular nerves (axons) and
      vascular endothelial cells. In the Sprague-Dawley rat cerebral basilar artery,
      positive labelling for nicotinamide adenine dinucleotide phosphate-diaphorase and
      nitric oxide synthase was localized in axons and the endothelium. Over half
      (approximately 53%) of the axon profiles examined were positive for nicotinamide
      adenine dinucleotide phosphate-diaphorase. Labelling of nicotinamide adenine
      dinucleotide phosphate-diaphorase activity in the axons and endothelial cells was
      mostly distributed in patches within the cytoplasm. In endothelial cells, a
      relation between the nicotinamide adenine dinucleotide phosphate-diaphorase
      labelling and cytoplasmic vesicle-like structures was seen. In both axons and the
      endothelium, nitric oxide synthase immunoreactivity was seen throughout the cell
      cytoplasm and in association with the membranes of mitochondria, endoplasmic
      reticulum and cytoplasmic/synaptic vesicles (the lumen/content of the vesicles
      was negative for nitric oxide synthase). Also, microtubules were labelled in
      nitric oxide synthase positive axon profiles. The nitric oxide synthase-positive
      axon varicosities were characterized by the presence of spherical agranular
      vesicles with a diameter of 40-50 nm. Approximately 30% of the axon profiles
      examined were positive for nitric oxide synthase. The nicotinamide adenine
      dinucleotide phosphate-diaphorase-positive endothelial cells (approximately 20%
      of all observed endothelial cell profiles) were more frequently seen than those
      positive for nitric oxide synthase (approximately 7%). It is suggested that
      nitric oxide released from both perivascular nerves and endothelial cells may be
      involved in vasomotor control of cerebral circulation.

PMID- 7513753
TI  - Posters: innovative and cost-effective tools for staff development.
AB  - Nursing staff development educators can use the poster as a time- and cost
      effective means to present essential information about policies and procedures as
      well as current, pertinent information about research findings. In this article,
      the authors present guidelines for preparation of successful poster
      presentations.

PMID- 7513752
TI  - Ionic conductances of monkey solitary cone inner segments.
AB  - 1. The membrane properties of cone inner segments dissociated enzymatically from
      monkey retina were studied under voltage-clamp conditions using patch pipettes in
      the whole-cell clamp configuration. 2. A noninactivating, voltage-gated calcium
      current was evoked at potentials positive to -60 mV and peaked between -30 and 
      20 mV when barium was substituted for calcium. Cadmium (50 microM) but not nickel
      (50 microM) blocked the current. 3. A large calcium-activated anion current (IAn)
      was observed when the membrane potential was set to a level between -60 and 30
      mV. The reversal potential of IAn was 0 mV with chloride as the sole anion and
      about -30 and -40 mV when methanesulfonate and D-aspartate, respectively,
      replaced intracellular chloride to set the equilibrium potential for chloride at 
      50 mV. IAn inactivated and oscillated when the membrane potential was maintained
      at depolarized levels, contrary to calcium-activated anionic currents seen in
      photoreceptors of other species. 4. A sustained-type potassium current was
      activated by depolarizations positive to -50 mV. The time course of activation
      and deactivation were voltage dependent. This potassium current was partially
      blocked by 20 mM tetraethylammonium ions. 5. A transient potassium current was
      activated by depolarizations positive to -20 mV. This current was blocked by 4
      aminopyridine (2 mM) and inactivated with a time constant of approximately 500
      ms. The amplitude in response to voltage steps to 45 mV was decreased by
      prepulses to voltages more positive than -30 mV. 6. Hyperpolarization negative to
      -65 mV activated an inward current that was completely blocked by external cesium
      (10 mM). The reversal potential suggested a conductance mechanism permeable to
      both sodium and potassium ions. 7. A calcium-activated potassium current, which
      was found in salamander photoreceptors, was not detected. 8. The presence of
      these conductances is expected to influence the membrane potential and the time
      course of the light response in monkey cones.

PMID- 7513751
TI  - Whole-cell analysis of ionic currents underlying the firing pattern of neurons in
      the gustatory zone of the nucleus tractus solitarii.
AB  - 1. Previous work from this laboratory has shown that rostral nucleus tractus
      solitarii (rNTS) neurons can be separated into four different classes on the
      basis of responses to a current injection paradigm consisting of membrane
      hyperpolarization immediately followed by a depolarizing pulse. These classes
      have been termed Group I, II, III, and IV neurons. The regular repetitive firing
      discharge pattern of Group I cells is changed into an irregular spike train by
      membrane hyperpolarization. Hyperpolarization of Group II neurons delays the
      firing discharge induced by depolarization. Hyperpolarization had the least
      effect on the discharge pattern of Group III neurons. The discharge pattern of
      Group IV neurons consisted of a short burst of spikes. We used whole-cell
      recordings and pharmacological channel blockers in an in vitro brain stem slice
      preparation to determine the ionic basis for the repetitive firing properties of
      rNTS neurons. 2. Application of 4-aminopyridine (4-AP, 1 mM) decreased input
      resistance and increased action potential duration in all groups of neurons.
      However, the discharge pattern of Group I, III, and IV neurons was either
      unaltered or slightly modified by 4-AP. In contrast the delay in firing of Group
      II cells induced by hyperpolarization was strongly reduced and in some cases
      completely suppressed by application of 4-AP. This suggests that a 4-AP-sensitive
      conductance primarily underlies the firing pattern of Group II cells. 3. Voltage
      clamp recordings revealed that the delay in Group II neurons is due to a
      transient outward potassium current that is partially inactivated around the
      resting membrane potential. Hyperpolarization removed this inactivation, causing
      a delay in the firing of the cell. The potassium current was blocked by 4-AP. A
      similar current was occasionally seen in neurons of the other groups. On the
      basis of its voltage and pharmacological dependence this current was presumed to
      be an A-current (IKA). 4. Blockade of calcium currents by a low-calcium (0.5 mM)
      saline containing 2 mM Co2+ depressed the excitability of rNTS cells. For Group
      II neurons the delay in firing activity was increased. In the other groups the
      repetitive firing pattern was suppressed. In addition the amplitude of the
      afterhyperpolarization occurring after a short train of action potentials was
      substantially reduced. This indicates that calcium currents (ICa) and calcium
      activated potassium currents (IKCa) contribute to the repetitive firing
      properties of rNTS neurons. 5. In about half of Group I, III, and IV neurons an
      additional property was found.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7513754
TI  - What is the efficacy of lumbar epidural steroid injections in the treatment of
      low back pain? If they are given, should they be given under radiographic
      guidance?

PMID- 7513755
TI  - Acquisition of Pseudomonas cepacia at summer camps for patients with cystic
      fibrosis. Summer Camp Study Group.
AB  - To assess the risk of acquisition of Pseudomonas cepacia by person-to-person
      transmission at cystic fibrosis summer camps, we conducted in 1990 a study at
      three camps attended by patients with cystic fibrosis who had P. cepacia
      infection and patients without P. cepacia infection but who were considered
      susceptible to infection. We obtained sputum or throat cultures from campers on
      their arrival at, weekly during, at the end of, and 14 to 30 days after camp. We
      compared the incidence of sputum conversion of patients at camp with that of
      patients outside camp by culturing specimens from noncamper control subjects with
      cystic fibrosis who were known not to be infected < or = 2 weeks before and 4 to
      6 weeks after camp. We also determined the risk factors for P. cepacia
      acquisition by determining the relative risk of acquisition between campers who
      were exposed versus campers who were not exposed to campers known to be infected
      or to potential environmental sources of P. cepacia at camp. The ribotype of P.
      cepacia isolates from campers with sputum conversion was compared with that of
      isolates from other campers and from an environmental source. The cumulative
      incidence of sputum conversion during the study period was 6.1% (11/181) among
      campers compared with no incidence (0/92) among noncampers (p = 0.02, Fisher
      Exact Test). The incidence of sputum conversion at camp varied according to the
      prevalence of campers with known infection (p < 0.001, chi-square test for
      trend). The rate of sputum conversion was higher in the camp with longer duration
      (relative risk = 12.0; 95% confidence interval = 2.7 to 53.5). Ribotyping showed
      that P. cepacia isolates from all 11 campers with sputum conversion were
      identical or similar (1 to 2 band difference) to isolates of other P. cepacia
      infected campers including co-converters. These results suggest that P. cepacia
      can be acquired by patients with cystic fibrosis who are attending summer camp
      for such patients, possibly through person-to-person transmission, and that the
      risk increases with the prevalence of P. cepacia-infected campers and the
      duration of camp.

PMID- 7513756
TI  - Prenatal cocaine exposure: nine years later.

PMID- 7513758
TI  - Impact of nutritional rehabilitation on gastroesophageal reflux in neurologically
      impaired children.
AB  - The impact of nutritional rehabilitation on gastroesophageal reflux (GER) in 10
      malnourished neurologically impaired children (NIC) was studied (mean age, 9.1 +/
      3.1 years). None of the children had an antireflux procedure (ARP), and all were
      fed exclusively through a percutaneous endoscopic gastrostomy (PEG). Malnutrition
      was defined as triceps skin fold thickness (TSF) below the fifth percentile for
      age and sex. GER was established using standard criteria for a 24-hour pH probe
      study. All children were treated with an H2 antagonist and a prokinetic agent,
      along with aggressive nutritional rehabilitation. When TSF was > or = 50th
      percentile, medications were stopped, and the 24-hour pH probe study was
      repeated. The mean weight gain was 8.8 +/- 3.7 kg over 8.4 +/- 2.3 months. The 24
      hour pH probe study showed marked improvement after nutritional rehabilitation in
      six of 10 children. These children remained asymptomatic throughout long-term
      follow-up, without the use of medications. Two children had abnormal pH probe
      results and worsening clinical symptoms when taken off medications after
      nutritional rehabilitation. They were reexamined after reinstituting the
      prokinetic drug; results of the pH probe study were normal, and there was no
      clinical symptomatology. The patients were then given long-term medication. Two
      children (one with erosive esophagitis and one with persistent symptoms)
      underwent ARP. We conclude that despite accompanying GER, successful nutritional
      rehabilitation can be achieved in malnourished NIC, using PEG feeding and
      antireflux medication. Although some NIC with GER may need an ARP or long-term
      medication, in most malnourished NIC nutritional rehabilitation is associated
      with resolution of GER.

PMID- 7513757
TI  - Increased incidence of intraventricular hemorrhage and developmental delay in
      cocaine-exposed, very low birth weight infants.
AB  - This study sought to determine whether very low birth weight (VLBW) infants (<
      1500 gm) with fetal cocaine exposure differed from non-cocaine-exposed VLBW
      infants in incidence of neonatal medical complications and in later developmental
      outcome. Forty-one cocaine-exposed, VLBW infants, followed in a longitudinal
      study, were compared with 41 non-cocaine-exposed, VLBW infants of comparable
      race, social class, age, and incidence of bronchopulmonary dysplasia. Cocaine
      exposed infants were identified on the basis of combined findings of maternal
      and/or infant urine immunoassay and on the basis of maternal self-report. At
      birth, groups did not differ on medical risk factors except that cocaine-exposed
      infants had a higher incidence of mild (grades I to II) intraventricular
      hemorrhage. Cocaine-using women were also more likely to use other drugs,
      especially alcohol, marijuana, and tobacco. At follow-up, at mean corrected ages
      of 16.5 +/- 8 months for 30 cocaine-exposed infants and 18.5 +/- 7 months for 37
      non-cocaine-exposed infants, standardized assessments of cognitive (Mental
      Development Index) and motor (Psychomotor Development Index) development were
      administered. Cocaine-exposed infants had lower mean cognitive (83 +/- 27 vs 91
      +/- 19), and motor (85 +/- 25 vs 96 +/- 18) scores; the incidence of
      developmental delay was significantly higher even after control for the effects
      of intraventricular hemorrhage and chronologic age. Cocaine-exposed VLBW infants
      were also more likely to be living with relatives or in foster homes. We conclude
      that these VLBW, cocaine-exposed infants were at increased risk of
      intraventricular hemorrhage, were more likely to be placed outside maternal care,
      and had higher incidences of cognitive and motor delays at follow-up.

PMID- 7513759
TI  - Abnormalities of nitric-oxide-producing neurons in Hirschsprung's disease:
      morphology and implications.
AB  - Nitric oxide (NO) is a recently discovered neurotransmitter that is thought to
      mediate relaxation of gut smooth muscle during peristalsis. To assess its role in
      the pathophysiology of Hirschsprung's disease, the authors examined the
      distribution of neurons that produce NO in specimens from seven infants with this
      condition. Immunohistochemical analysis of cryostat sections for nitric oxide
      synthase (NOS) immunoreactivity (NOS catalyzes the production of NO) showed that
      NOS is localized in a substantial subpopulation of enteric neurons in both the
      myenteric and submucosal plexuses in the ganglionated gut, but it was completely
      absent in aganglionic bowel. NOS immunoreactivity specifically colocalizes in
      neurons that also contain NADPH-diaphorase activity. This finding enabled the
      distribution of NO-producing neurons to be determined using whole-mount
      histochemistry, a technique that allows the enteric neural network to be examined
      intact. In normal bowel, NO-producing neurons are arranged in star-shaped
      myenteric and submucosal ganglia, which are joined to one another by nerve fibers
      to form a meshwork of variable geometry. Individual neurons exhibit Dogiel type 1
      morphology. Axonal processes leave the myenteric plexuses and lie parallel to
      muscle bundles in both muscle layers of the gut. In the transition zone, ganglia
      are initially present, but their orientation changes so that both they and the
      internodal strands that connect them are aligned linearly along the craniocaudal
      axis of the gut tube. More distal still, ganglia and then all NOS activity
      disappear completely. These results suggest that in Hirschsprung's disease, the
      failure of aganglionic bowel to relax during peristalsis might be caused by the
      absence of NO-producing neurons.

PMID- 7513760
TI  - Development and evaluation of an HIV-1 transfection-neutralization assay.
AB  - We developed a transfection-neutralization assay for human immunodeficiency virus
      type 1 (HIV-1) infectious molecular clones. In this assay CD4 negative adherent
      cells, transfected in microtiter plates with fixed amounts of proviral DNA of
      molecular HIV-1 clones, are cocultivated with CD4 positive T cell lines or
      primary peripheral blood mononuclear cells (PBMC) in the presence of anti-HIV-1
      sera or monoclonal antibodies (MAbs). Results obtained with this technique were
      reproducible and compared favorably with a conventional cell-free infection
      inhibition assay. The transfection-neutralization assay obviates the need for
      virus stock preparation and, therefore, is particularly suitable for the
      evaluation of HIV-1 clones with slow replication kinetics and of recombinant
      chimeric HIV-1 clones inclined to undergo additional mutations during stock
      preparation. The potential value of this assay for the analysis of the
      specificity of neutralizing sera and MAbs was demonstrated in experiments with V3
      chimeric molecular clones.

PMID- 7513761
TI  - Inhibition of human immunodeficiency virus type 1 activity in vitro by
      oligonucleotides composed entirely of guanosine and thymidine.
AB  - Oligonucleotide compounds composed of only deoxyguanosine and deoxythymidine were
      able to significantly inhibit human immunodeficiency virus type -1 (HIV-1)
      induced syncytium formation and virus production (as measured by p24 core antigen
      expression) in an acute infection assay system. The oligonucleotides did not
      share any homology with or possess any complementary (antisense) sequence motifs
      to the HIV-1 genome. The guanosine/thymidine-containing oligonucleotides (GTOs)
      that showed this anti-HIV activity contained natural phosphodiester (PD) linkages
      (backbones) between the nucleosides. One of the PD oligonucleotide sequence
      motifs tested was capable of inhibiting HIV-1-induced syncytium formation and p24
      production with a median effective dose in culture (ED50) in the submicromolar
      range. In addition, oligonucleotides tested were able to significantly suppress
      HIV-1 p24 levels > or = 7 days after removal of the drug from the infected cell
      culture medium. The growth inhibition properties (toxicity) of this genre of
      oligonucleotides was determined to be well above the ED50 values yielding high
      selective indexes. In vitro results showed that GTOs with PD backbones were
      potent competitive inhibitors of HIV-1 reverse transcriptase. These same
      molecules were capable of blocking the interaction between gp120 and CD4. All
      measured activities of these molecules were increased by factors of 10-500 when
      the PD backbone was replaced with a PT backbone in a sequence-dependent manner.
      The enhanced antiviral activity displayed by the sulfur group on the
      oligonucleotide backbone and the lack of any sequence-specific interactions
      suggest that a percentage of antiviral activity of oligonucleotide-based
      therapeutics is due to mechanisms other than those originally postulated for
      oligonucleotides. The good selective index of GTOs coupled with the prolonged
      suppression of HIV-1 in culture after removal of oligonucleotides from the
      infected cell culture make this a class of compounds that warrant investigation
      as therapeutic agents to be used against HIV-1.

PMID- 7513762
TI  - Immunoglobulin class and subclass antibodies to HIV proteins in maternal serum:
      association with perinatal transmission.
AB  - A flow cytometry-based assay for detection of immunoglobulin (Ig) class and
      subclass antibodies in human serum or plasma was developed. With use of this
      procedure, the presence and relative frequency of antibody activity in the Ig
      classes and subclasses (IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, and IgM) to
      human immunodeficiency virus type 1 (HIV-1) proteins (gp160, gp120, p66, and p24)
      was determined in serum or plasma from a cohort of 47 HIV-1-infected, pregnant
      women. Antibody activity in each of the classes and subclasses was found with
      differences in frequency depending on the Ig class/subclass and the HIV-1
      protein. IgG1 antibodies were the most frequently reactive Ig class/subclass to
      each protein. Intermediate frequencies of reactivity were found in IgA1, IgG2,
      IgG3, and IgM class and subclasses and antibodies of the IgA2, IgE, and IgG4
      class/subclass the least frequently detected. An unexpected finding was the
      presence of IgD antibodies to HIV-1 proteins in approximately 50% of the
      individuals. The distributions of Ig class/subclass antibodies to the different
      HIV-1 proteins were compared in sera from 14 mothers giving birth to infants who
      were determined to be HIV-1 infected with sera from 25 individuals whose infants
      were not infected. Sera from transmitting mothers contained a broader
      distribution of class and subclass antibodies compared to sera from
      nontransmitting women. The single most frequent antibody-antigen combination that
      was found in the transmitting mother was IgG2-gp160.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7513763
TI  - Identification of L-tryptophan derivatives with potent and selective antagonist
      activity at the NK1 receptor.
AB  - As part of a program of screening the Merck sample collection, N-ethyl-L
      tryptophan benzyl ester was identified as a weak antagonist at the substance P
      (NK1) receptor. Structure-activity studies showed that the indole ring system
      could be replaced by 3,4-dichlorophenyl, alpha- or beta-naphthyl, or
      benzthiophene with retention or only small loss of affinity. It was found that
      acylation of the tryptophan nitrogen gave compounds with higher affinity than N
      ethyl or other basic amines. Optimization of substitution on the benzyl ester led
      to the identification of the 3,5-bis-(trifluoromethyl)benzyl ester of N-acetyl-L
      tryptophan 26 as a potent and selective substance P receptor antagonist. Compound
      26 blocked substance P induced dermal extravasation in vivo and was the most
      potent compound from this structurally novel class of antagonists which further
      adds to the diversity of small molecules that bind to the (NK1) receptor.

PMID- 7513764
TI  - Tenascin mRNA isoforms in the developing mouse brain.
AB  - The extracellular matrix glycoprotein tenascin is expressed in the developing
      mouse cerebellum as a group of four protein species of different molecular
      weights. The difference is most likely due to alternative splicing which is known
      to occur in tenascin mRNA within the region of the fibronectin type III repeats.
      In order to systematically analyze tenascin mRNA isoforms that would account for
      this heterogeneity, tenascin splice variants were isolated from mouse brain by
      the polymerase chain reaction (PCR). In agreement with Northern blot analysis,
      amplification by PCR revealed a general decrease in tenascin mRNA expression
      during development from embryonic and early postnatal to adult stages. This
      decrease was more pronounced for isoforms of high molecular weight compared to
      those of low molecular weight. In accord with the observations at the protein
      level, four splice variants were found to be predominantly expressed, containing
      insertions of either six, five, or one fibronectin type III repeat, or comprising
      no insertion. In addition, a minor splice variant with an insertion of four
      fibronectin type III repeats was isolated. Three of the isolated mRNA splice
      variants have not yet been described for mouse tenascin. Among them, an isoform
      containing six alternatively spliced repeats was found to include a novel
      fibronectin type III repeat. The sequence of this repeat displays 96.7%
      similarity to a corresponding type III repeat in human tenascin, revealing a
      strict evolutionary conservation between tenascin molecules from different
      species in the region of alternative splicing. Southern blot analysis of the
      amplified mRNA isoforms showed that the novel mouse type III repeat is confined
      to splice variants with an insertion of six fibronectin type III repeats.
      Furthermore, in situ hybridization on sections from mouse embryos indicated that
      tenascin-specific mRNAs containing the novel type III repeat are predominantly
      expressed in the central nervous system.

PMID- 7513765
TI  - Cloning and expression of inducible nitric oxide synthase from rat astrocytes.
AB  - In primary cultures of rat astroglial cells exposure to bacterial endotoxin
      lipopolysaccharide (LPS) causes induction of a Ca(2+)-independent form of the
      nitric oxide synthase (iNOS) enzyme. We have now cloned the mRNA encoding
      astroglial iNOS using a combination of cDNA library screening and polymerase
      chain reaction (PCR) amplification with degenerate oligonucleotides directed
      against conserved regions of all NOS enzymes. The sequence of astroglial iNOS
      cDNA is highly similar to the mouse macrophage sequence, having an overall
      homology of 92% at the DNA level and 93% at the protein level. As in other NOSs,
      canonical binding sites for redox cofactors are present. The 3'-untranslated
      region displays 4 consensus AU-pentamers, 2 polyadenylation sites, and terminates
      in a stretch of 17 adenosine residues. In situ hybridization studies with LPS
      treated astrocyte cultures demonstrated the presence of iNOS mRNA in the majority
      of astroglial cells, identified by antibody staining to the glial fibrillary
      acidic protein (GFAP). PCR analysis showed that LPS stimulated synthesis of
      astrocyte iNOS mRNA, which was detected as early as 2 hr after exposure to LPS,
      peaked at 4 hr, and slowly declined over the next 20 hr. These results confirm
      that astrocytes can express iNOS and provide tools for the subsequent analysis of
      iNOS gene expression in rodent brain.

PMID- 7513767
TI  - The altered expression of cytokeratin polypeptides in carcinomas of human
      bladder.
AB  - After extraction in high salt buffers and Triton X-100, cytokeratin polypeptides
      could be isolated from normal epithelium and transitional cell carcinoma of the
      human bladder in the southwestern coast of Taiwan. The polypeptides were
      solubilized via lysis buffer, separated by two-dimensional gel electrophoresis,
      and identified by immunoblot. Five cases of normal epithelium expressed
      cytokeratin No. 5 (58 kd), 7 (54 kd), 18 (45 kd) and one case further expressed
      cytokeratin No. 19 (40 kd) in addition to the above cytokeratins. Combined
      patterns of cytokeratin polypeptides were observed among various Grades of
      transitional cell carcinoma of bladder. Comparing the patterns between the normal
      epithelium and the transitional cell carcinoma of bladder, 88% (14/16) of
      carcinomas expressed cytokeratin No. 8 (52.5 kd) and 63% (10/16) expressed No. 17
      (46 kd), which were not seen in the normal epithelium. Some other cytokeratin
      polypeptides particular to carcinomas were No. 4 (59 kd), No. 10 (56.5 kd), No.
      13 (54 kd) and No. 14 (50 kd) and were only present in less than 50% (ranging
      from 31-56%) of the examined specimens. Thus cytokeratin No. 8 and 17 could be
      helpful markers for diagnosis of bladder carcinoma.

PMID- 7513766
TI  - Role for the stem cell factor/KIT complex in Schwann cell neoplasia and mast cell
      proliferation associated with neurofibromatosis.
AB  - Schwann cells are the primary cell type in the disfiguring lesions associated
      with neurofibromatosis type 1 (NF-1). These lesions also contain abnormally high
      numbers of mast cells, a cell type which develops in response to stem cell
      factor. We report here that neonatal and adult rat and human Schwann cells, as
      well as a transfected rat Schwann cell line and a human Schwannoma line derived
      from an NF-1 patient, all produced stem cell factor mRNA and protein. In
      coculture experiments, surface expression of stem cell factor by neonatal rat
      Schwann cells was profoundly downregulated by contact with dorsal root ganglion
      neurites. The receptor for stem cell factor, KIT, was not expressed in normal
      Schwann cells but was expressed in the human Schwannoma line, suggesting that
      aberrant KIT expression may form an autocrine loop in certain Schwann cell
      neoplasias.

PMID- 7513769
TI  - [Analysis of the preceding R-R interval and the coupling interval on premature
      ventricular contractions].
AB  - Premature Ventricular Contractions (PVCs) are one of the common arrhythmias.
      Although the analysis of the preceding R-R interval and the coupling interval on
      the Holter electrocardiogram, the Lorenz plotting method, has been used to
      characterize mature of PVC, this analysis has typically been performed without
      regard to the morphological classification of the electrocardiogram waveforms.
      Therefore, we performed the Lorenz plotting after a PVC classification. We
      analyzed 45 cases with more than 1,000 PVCs per day. Twenty-six of the cases with
      PVCs had no organic heart disease (idiopathic PVC); nineteen of the cases with
      PVCs had organic heart disease (PVC with disease). Each R-R interval was analyzed
      after classification based on the morphology of each QRS wave of the PVC. The
      computer generated a two-dimensional plot of the relationship between the
      preceding R-R interval of PVC and the following coupling interval. The forms of
      PVCs were monoform in idiopathic PVC and were mostly multiform in PVC with
      disease. The patterns on Lorenz plotting in idiopathic PVC had a tendency to be
      uniform with small standard deviations. In contrast, multiform PVCs tended to be
      highly variable with large standard deviations. The value of SD was 32.1 +/- 12.0
      msec in idiopathic PVC, and that of the slope "a" was 0.048 +/- 0.051 in PVC with
      disease. Using the SD values and the slope "a" values, we were able to classify
      idiopathic PVC vs. PVC with disease with a 95% sensitivity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7513768
TI  - Zollinger-Ellison syndrome. Advances in treatment of gastric hypersecretion and
      the gastrinoma.

PMID- 7513771
TI  - Neurodevelopmental abnormalities in school-age children with HIV infection.

PMID- 7513770
TI  - Expression of stem cell factor and its receptor, c-kit, during liver regeneration
      from putative stem cells in adult rat.
AB  - BACKGROUND: Stem cell factor (SCF) and its receptor, c-kit, are known to play
      important roles in hematopoiesis, melanogenesis, and gametogenesis. The biologic
      effects of the SCF/c-kit system are believed to involve survival, proliferation,
      and migration of early stem cell progeny. Although SCF and c-kit receptor are
      widely expressed during normal embryonic development, their expression in the
      adult is limited. EXPERIMENTAL DESIGN: The expression of SCF and c-kit genes was
      examined during liver regeneration via the oval cell compartment utilizing
      partial hepatectomy (PH) combined with the administration of a noncarcinogenic
      dose of 2-acetylaminofluorene (AAF) for 8 days (AAF/PH model). RESULTS: Both the
      ligand and the receptor genes were expressed during the early stages of oval cell
      proliferation after partial hepatectomy in the AAF/PH model, while neither simple
      partial hepatectomy nor AAF administration alone induced a noticeable expression
      of the SCF/c-kit system. The level of SCF mRNA increased within 12 hours after
      partial hepatectomy and reached a peak around day 4. Thus, the expression of SCF
      preceded the major expansion of the oval cell compartment. The level of c-kit
      transcripts gradually increased from the 12-hour time point and stayed elevated
      until day 11, when a large proportion of the oval cells differentiated into small
      basophilic hepatocytes. Separation of liver cells at day 3 in the AAF/PH model
      into parenchymal and nonparenchymal fractions demonstrated that the expression of
      both SCF and c-kit receptor genes was restricted to the nonparenchymal cells.
      Furthermore, in situ hybridization revealed that the c-kit transcripts were
      restricted to oval cells, whereas the SCF transcripts were expressed in both oval
      cells and Ito cells. CONCLUSIONS: The transcripts for the c-kit receptor are
      expressed in the early progeny of the hepatic stem cells. The SCF/c-kit system
      may, possibly in combination with other growth factor/receptor systems, be
      involved in the early activation of the hepatic stem cells as well as in the
      expansion and differentiation of oval cells.

PMID- 7513773
TI  - Effects of conformational elasticity and ion-channel interaction on thermodynamic
      equilibrium of biomembranes.
AB  - A theory of equilibrium states of a biomembrane with particles in its channels
      that takes into account "bilateral" channel-particle interactions has been
      developed within a thermodynamic scheme. The aim of the proposed theory is to
      explain the existence of the multiple steady states which have long been observed
      experimentally. The existence of such states is postulated in the majority of the
      current theories which kinetically describe transitions between such states. The
      governing equations have been derived from basic physics under the requirement
      that the conformation of the channel changes to minimize the system's free energy
      which includes the elastic conformation energy together with the electrostatic
      interaction between the (hydrated) ion and the channel. It has been shown that in
      certain regions of a control parameter such minimization can give rise to
      bifurcation of the equilibrium state, i.e. to the coexistence of at least two
      equilibrium states. The value of the control parameter can be changed by an
      external action (gating), which can be either mechanical, or electrical, or even
      thermal.

PMID- 7513772
TI  - Digital rectal examination, serum prostate specific antigen, and prostatic
      ultrasound: how effective is this diagnostic triad?
AB  - Ninety-nine of 105 consecutive men who underwent transrectal prostatic ultrasound
      (TRUS) at Highland Park Hospital had the results correlated with digital rectal
      examination (DRE), serum prostate specific antigen (PSA), and biopsy results.
      Ninety-six cases had evaluable ultrasound studies. Thirty-two of the 99 who
      underwent biopsy had primary carcinoma of the prostate. Prostate volume,
      predicted PSA, a ratio of observed/predicted PSA, and Gleason score were
      examined. There was no correlation between age and prostate volume, volume and
      the presence of carcinoma, or PSA and Gleason score. Thirty-one point six percent
      of the abnormal DREs, 36.6% of the abnormal TRUSs, and 40.6% of the elevated PSAs
      occurred in men with prostatic carcinoma (PCa). If PSA was normal (less than or
      equal to 4.0 ng/ml) and either DRE or TRUS was abnormal, then the risk of
      carcinoma was 2.9%. If PSA was elevated, regardless of the other two tests, the
      risk of finding PCa was at least 38%. If all three tests were abnormal, the risk
      of carcinoma was 38% in our series and 68% in a meta-analysis. Many men with PSA
      values between 4 and 10 ng/ml have benign biopsies. However, close future follow
      up with consideration of repeat biopsy should be strongly considered.

PMID- 7513774
TI  - Stress localization in the RNA backbone: a mechanical footprint for predicting
      base-backbone tertiary contacts.
AB  - A physico-chemical basis to understand the site-specificity of intramolecular
      nucleophilic attack in RNA self-splicing involves the identification of
      vulnerable backbone regions in addition to determining the proper placement of
      attacking groups. In preliminary relevant work we have introduced the decisive
      concept of structure-induced localized absorption of stress by backbone degrees
      of freedom. In this way we implemented a mechanical approach which incorporates
      the consensus structural information as a constraint and correctly identifies
      reactive sites as strain hot spots. In this work we turn this approach into a
      predictive tool to search for structural constraints which are necessary to
      localize strain at pre-determined splicing and cyclization sites. In particular,
      we identify tertiary base backbone contacts regarding them as appropriate
      constraints to the backbone mechanics. To implement our approach we introduce an
      effective Hamiltonian which governs the exploration of backbone conformation
      space by energetically penalizing structural distortions. We show how this
      Hamiltonian singles out specific regions of stress associated with reactive
      sites. As an illustration, we apply this working principle to a specific
      ribozyme, the cobI5 intron, for which the tertiary interactions predicted to be
      functional in 3' splicing have not been previously determined experimentally. To
      establish the predictive value of our approach, we identify the tertiary contacts
      that should be present in the cobI5 intron to serve as scaffolds stabilizing the
      conserved P10 secondary interaction and to introduce ribose conformational
      rigidity necessary to localize strain precisely at the 3' splicing site. Guided
      by our computations, the purported interactions are confirmed using deoxyribose
      substitution probes.

PMID- 7513775
TI  - Induction of intercellular adhesion molecule-1 and E-selectin mRNA in heart and
      skeletal muscle of pediatric patients undergoing cardiopulmonary bypass.
AB  - Leukocyte adhesion to vascular endothelium is an early step in inflammatory
      damage to tissues. To investigate the expression of endothelial adhesion
      molecules in the inflammatory response associated with cardiopulmonary bypass, we
      measured messenger ribonucleic acid (mRNA) encoding the adhesion molecules E
      selectin and intercellular adhesion molecule-1 in intraoperative samples of
      cardiac tissue and skeletal muscle from infants undergoing cardiopulmonary
      bypass. Atrial tissue samples were obtained before and after bypass from 11
      children and paired samples of rectus abdominis muscle from 15. mRNA was analyzed
      by ribonuclease protection with the use of nonmuscle actin as an internal
      control. Atrial E-selectin mRNA levels increased from before to after bypass
      (median increase 3.5-fold, p = 0.0002) in each of nine patients tested, and
      atrial intercellular adhesion molecule-1 mRNA increased in seven of nine patients
      (median, 2.1-fold, p = 0.025). In skeletal muscle, E-selectin mRNA increased in
      11 of 12 patients (median 4.3-fold, p = 0.0018), and intercellular adhesion
      molecule-1 mRNA levels increased in 13 of 13 patients (median 3.2-fold, p =
      0.013). E-selectin and intercellular adhesion molecule-1 induction in skeletal
      muscle occurred with or without circulatory arrest. We conclude that adhesion
      molecule mRNA induction occurs in cardiac and noncardiac tissue during
      cardiopulmonary bypass in man.

PMID- 7513776
TI  - Influence of aprotinin on the thrombomodulin/protein C system in pediatric
      cardiac operations.
AB  - Thirty consecutive children scheduled for pediatric cardiac operation with
      cardiopulmonary bypass were included in the study. Before the operation, the
      patients were randomly divided into two groups: with aprotinin (n = 15, 30,000
      U/kg after induction of anesthesia, 30,000 U/kg added to the prime of the
      cardiopulmonary bypass or without aprotinin (n = 15). Thrombomodulin, (free)
      protein S, protein C, and thrombin/antithrombin III complex were measured from
      arterial blood samples taken after induction of anesthesia (at baseline, before
      aprotinin) and before, during, and after cardiopulmonary bypass until the first
      postoperative day. Standard coagulation parameters (antithrombin III, fibrinogen,
      platelet count, and partial thromboplastin time) were without differences between
      the groups. Thrombomodulin plasma concentrations were within normal range ( < 40
      micrograms/L) and were similar in both groups at baseline. During cardiopulmonary
      bypass and until 5 hours after cardiopulmonary bypass, however, thrombomodulin
      plasma levels were significantly lower in the children treated with aprotinin. No
      further differences were observed on the first postoperative day. Protein C and
      protein S plasma levels did not differ between the two groups.
      Thrombin/antithrombin III-complex plasma concentrations increased significantly
      during cardiopulmonary bypass, however, without showing differences between
      children with (225 +/- 49 micrograms/L) and without (149 +/- 31 micrograms/L)
      aprotinin treatment. Blood loss and the need for homologous blood and blood
      products did not differ significantly between the two groups. We concluded that
      administration of aprotinin resulted in reduced thrombomodulin plasma levels in
      pediatric patients undergoing cardiac operation without altering protein
      C/protein S plasma concentration. The exact role of aprotinin in endothelium
      derived coagulation should be further studied.

PMID- 7513777
TI  - Surgery for tetralogy of Fallot at less than six months of age.
AB  - Absence of consensus persists regarding the optimal procedure and timing for the
      surgical treatment of young infants with symptomatic tetralogy of Fallot. From
      1987 through 1992, 56 patients with tetralogy of Fallot were operated on at less
      than 6 months of age. Forty-one patients (median age 2.9 months) underwent
      primary repair and 15 (median age 2.4 months) underwent initial palliation. Mean
      follow-up was 24.2 +/- 16.4 months. No strict protocol was used but patients who
      received initial palliation were younger, had a smaller pulmonary arterial tree,
      or had anomalous coronary artery. Two patients died (overall mortality 3.6%; 95%
      confidence limits 0% to 11%), one after initial palliation (6.7%), and one after
      primary repair (2.4%) (P = 0.47). Eight of the 15 patients who received initial
      palliation underwent repair and had an increase in pulmonary anulus size at the
      time of definitive repair (mean difference Z-value = 2.2 +/- 1.6 standard
      deviation; p = 0.006). Transannular patch was required in 50% of patients who
      underwent repair (56% among patients having primary repair versus 13% for
      patients having initial palliation; P = 0.03). Five patients underwent
      reoperation. Early primary repair of symptomatic tetralogy of Fallot was achieved
      with a low mortality rate and is the preferred protocol. Initial palliation
      remains indicated in case of associated cardiac anomaly, very low weight, or
      severely hypoplastic pulmonary artery tree.

PMID- 7513778
TI  - Possible toxicity with the association of G-CSF and bleomycin.

PMID- 7513779
TI  - Follow-up of children in the Italian Study of Aspirin in Pregnancy.

PMID- 7513781
TI  - Insulin-like growth factors (IGF)-I and -II and IGF binding protein-1, -2, and -3
      in patients with acromegaly before and after adenomectomy.
AB  - The interrelationship between insulin-like growth factors (IGFs) and their major
      binding proteins (IGFBPs) as a function of disease activity in acromegaly has not
      previously been prospectively evaluated. We studied basal and insulin-stimulated
      serum levels of IGF-I and -II and IGFBP-1, -2, and -3 in six acromegalic patients
      before and 2 months after successful adenomectomy compared with a group of sex-
      and age-matched healthy, untreated subjects. All were studied postabsorptively
      (11 AM) and at the end of a 2-hour euglycemic glucose clamp (0.4 mU insulin/kg x
      min). Serum IGF-I levels (mean +/- SE) were elevated in acromegaly but were
      normalized following therapy (basal state IGF-I [micrograms/L], 857 +/- 119
      [active] v 255 +/- 65 [postoperative] v 190 +/- 20 [control]). Serum IGF-II
      levels did not change following therapy and were similar to those of the control
      group. IGF levels did not change during the clamp. Serum IGFBP-3 levels were
      elevated in active acromegaly, but were normalized after therapy (basal state
      IGFBP-3 [micrograms/L] 6,983 +/- 612 [active] v 3,939 +/- 504 [postop] v 3,358 +/
      125 [control]). The molar ratio of (IGF-I+IGF-II): IGFBP-3 was similar in all
      studies. Serum IGFBP-1 interacted significantly with time in all studies,
      exhibiting a gradual decrease in the basal state and ensued by further
      suppression during the clamp. Insulin and IGFBP-1 correlated inversely in the
      pooled data and in the acromegalic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513782
TI  - Considering the alternatives.

PMID- 7513780
TI  - Effect of FK506 on rat Leydig cell function--in vivo and in vitro study.
AB  - FK506, a macrolide antibiotic, is a potent immunosuppressant and has a biological
      effect similar to that of cyclosporin A (CsA). In this study, the in vivo and in
      vitro effects of FK506 on rat Leydig cell function were investigated. In vivo,
      basal testosterone levels and secretion in response to human chorionic
      gonadotropin (hCG) stimulation in ACl rats treated with intramuscular (IM)
      injections of FK506 at a dosage of 1 or 2 mg/kg/d for 14 days were not different
      from those of age-matched normal controls. Testicular weights (g) from rats
      treated with 14 injections of 1 mg/kg/d FK506 (1.08 +/- 0.08, n = 14) were
      similar to weights from age-matched controls (1.04 +/- 0.08, n = 14). Similarly,
      Wistar (Wi) rats treated with FK506 at a dosage of 1 mg/kg/d for 2 weeks showed
      basal testosterone and luteinizing hormone (LH) levels and secretion in response
      to hCG stimulation similar to those of normal controls. Histologically, the
      Leydig cells and germ cells in FK506-treated animals appeared normal. In vitro,
      basal testosterone production and response to hCG stimulation by both ACI and Wi
      rat Leydig cells exposed to overnight treatment of FK506 (10 to 1,000 ng/mL) were
      not significantly different from those of control Leydig cells. Furthermore, the
      viability of the Leydig cells cultured for 3 days in FK506 was not significantly
      different from that of controls, and they continued to secrete testosterone at a
      rate similar to that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513783
TI  - [Role of neutrophils in warm renal ischemia and reperfusion injury in the rat].
AB  - This study attempts to determine whether the circulating neutrophils play a role
      in mediating injury resulting from renal ischemia, using rats treated with
      cyclophosphamide (CY) and/or granulocyte colony-stimulating factor (G-CSF). The
      neutrophil counts immediately before 60-minute ischemia decreased by 89% in the
      CY-treated rats in comparison with the untreated animals (p < 0.01). In the rats
      given G-CSF with CY, the neutrophil counts significantly increased over that of
      the CY-treated rats (p < 0.01). The serum creatinine level 24 hours after
      reperfusion amounted to 4.42 +/- 0.37 mg/dl in the control rats and 2.63 +/- 0.29
      mg/dl in the CY-treated rats (p < 0.01). In 19 rats, 10 controls and the 9 CY
      treated, the neutrophil counts immediately before ischemia correlated well with
      the serum creatinine levels 24 hours after reperfusion (r = 0.597; p < 0.01). Our
      results appear to indicate that neutrophils play an important role in warm
      ischemia and reperfusion injury of the kidney.

PMID- 7513785
TI  - Special issue: Professor F.H. Sobels memorial issue.

PMID- 7513784
TI  - New killing system controlled by two genes located immediately upstream of the
      mukB gene in Escherichia coli.
AB  - The nucleotide sequence was determined of the region upstream of the mukB gene of
      Escherichia coli. Two new genes were found, designated kicA and kicB (killing of
      cell); the gene order is kicB-kicA-mukB. Promoter activities were detected in the
      regions immediately upstream of kicB and kicA, but not in front of mukB. Gene
      disruption experiments revealed that the kicA disruptant was nonviable, but the
      kicB-disrupted mutant and the mutant lacking both the kicB and kicA genes were
      able to grow. When kicA disruptant cells bearing a temperature-sensitive
      replication plasmid carrying the kicA+ gene were grown at 30 degrees C and then
      transferred to 42 degrees C, the mutant cells gradually lost colony-forming
      ability, even in the presence of a mukB+ plasmid. Rates of protein synthesis, but
      not of RNA or DNA synthesis, fell dramatically during incubation at 42 degrees C.
      These results suggested that the kicB gene encodes a killing factor and the kicA
      gene codes for a protein that suppresses the killing function of the kicB gene
      product. It was also demonstrated that KicA and KicB can function as a post
      segregational killing system, when the genes are transferred from the E. coli
      chromosome onto a plasmid.

PMID- 7513786
TI  - Dissociation between radioresistant DNA replication and chromosomal
      radiosensitivity in ataxia telangiectasia cells.
AB  - Ataxia telangiectasia (AT) skin fibroblasts in G1 phase and peripheral blood
      lymphocytes in G0 and G1 phase were studied for their DNA replication response to
      X-rays. The irradiation of normal cells in G1 but not in G0 phase caused a delay
      of onset of DNA replication, which was less pronounced in AT cells. However, such
      radioresistant DNA replication itself cannot be the sole mechanism of the
      increased sensitivity of AT cells to chromosome aberration formation by X-rays
      for the following two reasons: (1) due to the intrinsically slow cell cycle
      progression of AT fibroblasts, the time of traverse to DNA replication of AT
      cells was comparable with that of normal cells after exposure to 1 Gy while AT
      cells gave rise to a greatly increased number of chromatid aberrations; (2) in
      peripheral blood lymphocytes irradiated in G0 phase, the traversal to the DNA
      replication phase was the same for normal and AT cells in spite of the well
      documented chromosomal radiosensitivity of G0-irradiated AT cells. The AT factor
      may be better explained as a key element directly involved in DNA damage
      processing, which in turn provides messages to suppress replication if
      recombination and replication are mutually exclusive.

PMID- 7513788
TI  - How variable is a spontaneous mutation rate in cultured mammalian cells?
AB  - The Luria-Delbruck fluctuation analysis provides a method to estimate mutation
      rates and is commonly applied in somatic cell genetics and in cancer biology. We
      developed an assay for a Luria-Delbruck fluctuation analysis using the mouse
      lymphoma cell line, GRSL13. As these cells grow in suspension, one can handle
      hundreds of parallel cultures using multiwell dishes and dispensers. This assay
      thereby allows not only an accurate determination of the mutation rate per cell
      generation but also makes it possible to determine at which time after seeding
      mutations take place. Using approx. 8000 parallel cultures it has been possible
      to test whether the mutation rate is constant during the assay. It has been found
      that the spontaneous mutation rate of GRSL13 cells decreases in the course of a
      fluctuation test from 2 x 10(-6) to about 2 x 10(-7)/cell/generation. It was
      shown that this increased replication fidelity may partly be caused by cell
      density: maintenance of cells at high cell density resulted in a spontaneous
      mutation rate of 0.7 +/- 4.0 x 10(-7) compared to 4.0 +/- 3.1 x 10(-7) for the
      standard protocol. In contrast, growing the cells at extremely low cell density
      resulted in an enhanced mutation rate of 7.7 +/- 1.3 x 10(-7). Thus altogether
      the mutation rate can vary from 2 x 10(-6) to 0.7 x 10(-7) (approx. 30-fold).
      These results show that the spontaneous mutation rate is not constant, but highly
      dependent on experimental conditions. As incomplete expression and metabolic
      cooperation cannot explain the findings, the data suggest that the fidelity of
      DNA replication is not fixed but open to variation. Hence, determination of
      replication infidelity in cultured cells needs rigorous standardization or/and
      application of controlled variation in culture conditions.

PMID- 7513787
TI  - Regulatory processes and the origins of spontaneous mutations.
AB  - A review of information currently available about the origins of spontaneous
      mutational events suggests that there may be a role for known cellular control
      mechanisms in determining the frequencies with which such events can occur.
      Attention is also directed to recent findings with antimutator (dnaE) mutants of
      Escherichia coli which indicate that the final step involved in generating a
      spontaneous mutational event may be different from that involved in generating an
      SOS-dependent mutational event. Finally, the possible involvement of various
      sorts of treatments collectively referred to as stress responses (heat shock,
      cold shock or oxidative damage, etc.) in generating random mutations is
      discussed; if there is such an involvement, this may represent one way in which
      organisms are programmed to adapt to a wide variety of environmental challenges.

PMID- 7513789
TI  - Origins of spontaneous base substitutions.
AB  - Although simple to understand, satisfying to the imagination, and compelling as a
      teaching aid for beginning students, the evidence is mounting that the tautomeric
      shift is neither a common nor a likely origin for spontaneous base substitutions.
      Indeed, other sources, such as ionized base mispairings with nonionized bases,
      wobble of a bases in the DNA, and transient misalignment of bases causing
      dislocations at pairing sites, have been shown to induce spontaneous base
      substitutions. On the other hand, among the 4 common bases in DNA, no
      experimental evidence exists that tautomeric shifts can induce mutations.

PMID- 7513790
TI  - Structure-activity studies in E. coli strains on ochratoxin A (OTA) and its
      analogues implicate a genotoxic free radical and a cytotoxic thiol derivative as
      reactive metabolites.
AB  - Ochratoxin A (OTA), its major metabolite in rodents, ochratoxin alpha, and seven
      structurally related substances were assayed for SOS DNA repair inducing activity
      in Escherichia coli strain PQ37. At concentrations of 0.1-4 mM, OTA, chloroxine,
      5-chloro-8-quinolinol, 4-chloro-meta-cresol and chloroxylenol induced SOS DNA
      repair in the absence of an exogenous metabolic activation system. Ochratoxin B,
      ochratoxin alpha, 5-chlorosalicylic acid and citrinin were inactive, but all
      except ochratoxin alpha were cytotoxic. Thus, the presence of chlorine at C-5
      appears to be one determinant of genotoxicity in these substances. Amino
      oxyacetic acid, an inhibitor of the cysteine conjugate beta-lyase, decreased the
      cytotoxicity of OTA but did not alter its genotoxic activity, suggesting the
      formation of a cytotoxic thiol-containing derivative. The mechanisms by which OTA
      and some of its active analogues induce SOS DNA repair activity was further
      investigated in E. coli PQ37 and in three derived strains (PQ300, OG100 and
      OG400), containing deletions within the oxy R regulon. The response in strain
      PQ37 was measured in the absence and presence of Trolox C, a water-soluble form
      of vitamin E. Trolox C completely quenched the genotoxicity of OTA, and the
      effect was similar in the mutant and wild-type strains. These results implicate
      an OTA-derived free radical rather than reduced oxygen species as genotoxic
      intermediate(s) in bacteria.

PMID- 7513791
TI  - Starvation-associated mutation in Escherichia coli: a spontaneous lesion
      hypothesis for "directed" mutation.
AB  - When stationary phase E. coli WU3610, carrying an ochre mutation in the tyrA
      gene, were incubated on plates lacking tyrosine, tyrosine-independent (Tyr+)
      mutants appeared from day 7 onwards in a time-dependent manner. These starvation
      associated mutants did not contain either identifiable tRNA suppressors or
      reversions at the ochre site and are thus quite distinct from the mutants
      commonly found to arise during active growth. When an appropriate fluctuation
      assay protocol was employed slow growing Tyr+ mutants were also found to arise in
      growing cells, and their distribution was more characteristic of a replication
      dependent than a time-dependent process. The rate of appearance of starvation
      associated mutants at 37 degrees C was somewhat less than at 27 degrees C and
      this was attributed to a reduction in viability at the higher temperature. There
      was no evidence for the accumulation on the plates of mutations in other genes.
      Tyr+ mutants were, however, shown to arise during incubation of stationary phase
      cells under conditions where there was no selection for tyrosine independence,
      provided outgrowth was subsequently permitted on plates lacking tyrosine. This
      distinguishes the present system from those systems exhibiting genuine "directed"
      or "adaptive" mutation, should they exist. To explain the specificity which
      occurs, it is proposed that the appearance of stationary mutants in ochre strains
      reflects the time-dependent accumulation in the transcribed strand of a DNA
      lesion that has a high probability of miscoding during transcription and
      replication. A mutant RNA transcript permits protein synthesis which in turn
      triggers DNA replication. The mutation is then fixed in the DNA as a permanent
      heritable change. The apparent "directedness" of the process is, on this model,
      determined solely by the particular miscoding DNA lesion occurring in a
      transcribed strand at a site where a change in phenotype permits DNA replication
      to occur.

PMID- 7513792
TI  - The molecular basis of nucleotide excision repair syndromes.

PMID- 7513793
TI  - Inhibition of the 'spontaneous' mutagenicity in Salmonella typhimurium TA102 and
      TA104.
AB  - Thirty-four compounds belonging to various chemical classes were assayed for the
      ability to modulate the 'spontaneous' mutagenicity in strain TA104 of S.
      typhimurium, and 17 of them were also assayed in TA102. All test agents, many of
      which were already known or suspected to act as inhibitors of induced
      mutagenicity, had been previously monitored in our laboratory for
      antimutagenicity towards either 4-nitroquinoline 1-oxide in TA100 and/or
      cigarette smoke in TA98 with S9 mix. A considerable proportion of test compounds
      decreased the number of spontaneous revertants in TA104 (44.1%) and/or TA102
      (41.2%) to a significant extent, with dose-related and reproducible effects. In
      almost all cases the antimutagenic effect was genuine and not related to
      bacterial killing or growth inhibition. The results obtained suggest that the DNA
      repair background plays a prominent role in the genesis of spontaneous mutations
      in these strains, containing the hisG428 mutation which is typically reverted by
      oxidative mutagens. Due to its theoretical and practical implications, the
      finding that several chemopreventive agents can attenuate the rate of spontaneous
      reversion deserves attention.

PMID- 7513794
TI  - Response of the Muta mouse lacZ/galE- transgenic mutation assay to DMN:
      comparisons with the corresponding Big Blue (lacI) responses.
AB  - The lacZ Muta mouse transgenic mutation assay was recently adapted into a
      selective assay based on use of E. coli galE(-) bacteria and phenyl galactoside
      (p-gal). A preliminary assessment of this selective assay was undertaken using a
      single oral dose of 10 mg/kg of dimethyl nitrosamine (DMN). The livers of treated
      male mice were assessed for UDS 2 h after dosing, and for lacZ- mutations 7, 11
      and 20 days after dosing. A strong UDS response was recorded and a clear
      mutagenic response was observed at each of the 3 timepoints. Comparison of these
      data with earlier data derived using the Big Blue (lacI) mutation assay reveals a
      marginally greater sensitivity to DMN of the selective Muta mouse assay, an
      effect probably related to a biochemical difference between the strains of
      animal, as evidenced by the larger UDS response seen in the Muta mouse system.
      The original Muta mouse assay protocol was impractical. The galE- adaption makes
      the assay emminently practical and cost-effective. We are continuing to assess
      the true role of both the Big Blue assay and the galE- Muta mouse assay in
      mutagenicity/carcinogenicity prediction. The former assay enables access to
      B6C3F1 mice and F344 rats, the latter enables the rapid acquisition of data.

PMID- 7513795
TI  - X-ray-induced specific-locus mutations in the ad-3 region of two-component
      heterokaryons of Neurospora crassa. XII. Analysis of multiple-locus ad-3
      mutations reveals a nonrandom distribution of the separate sites of recessive
      lethal damage throughout the genome.
AB  - Previous studies on X-ray-induced adenine-3 mutations induced in heterokaryon 12
      of Neurospora crassa showed that they consisted of gene/point mutations,
      multilocus deletion mutations, and 3 different genotypic classes of multiple
      locus mutations (designated [-3]IR + RLCL, ad-3R + RLCL, and ad-3R + RL). In the
      present paper, multiple-locus mutations consisting of gene/point mutations at the
      ad-3A or the ad-3B locus with sites of recessive lethal damage closely linked to
      the ad-3 region (designated ad-3R + RLCL) or with sites of recessive lethal
      damage elsewhere in the genome (designated ad-3R + RL) were analyzed to determine
      whether they resulted from mutations at the same sites or different sites
      throughout the genome. It was assumed that if the recessive lethal mutations in
      individual multiple-locus mutations showed complementation on adenine
      supplemented medium, they resulted from mutations at different sites. Multiple
      locus mutations from both major genotypic classes were combined, as forced
      heterokaryons, in all possible pairwise combinations and then were plated out on
      adenine-supplemented medium. These studies indicated that 89.3% (50/56) of the
      recessive lethal mutations in these 2 classes of multiple-locus mutations
      complement one another. Thus, they are presumed to have resulted predominantly
      from genetic damage at different sites throughout the genome. Within the group of
      20 multiple-locus mutations that did not complement in various pairwise
      combinations, 90% (18/20) appear to map in a region, distal to the ad-3 region,
      defined by a series of overlapping multilocus deletion mutations in 6 mutations
      of genotype ad-3R + RLCL. The other 10% (2/20) are located elsewhere on Linkage
      Group I or elsewhere in the genome. The present data base on multiple-locus
      mutations is unique; such events either can not be detected, or can only be
      detected with difficulty, in other eukaryotic specific-locus assay systems such
      as mammalian cells in culture, Drosophila or mice. Our data on X-ray-induced ad-3
      specific-locus mutations from the present and previous studies demonstrate the
      presence of additional sites of genetic damage, both closely linked with the ad-3
      region or elsewhere in the genome, in ad-3 specific-locus mutations. Because the
      frequencies of each class of multiple-locus mutations is dose-dependent, they
      must be taken into account in genetic risk assessment exercises. Failure to
      acknowledge the presence of such additional sites of genetic damage in the
      utilization of specific-locus data could result in underestimation of the risk of
      human exposure to environmental mutagens.

PMID- 7513796
TI  - Characterization of 4-nitro-o-phenylenediamine activation by plant systems.
AB  - 4-Nitro-o-phenylenediamine (NOP) is a powerful direct-acting mutagen which
      demonstrates significant enhancement in mutagenicity when exposed to plant
      enzymatic systems. Evidence implicating the involvement of peroxidactic oxidation
      in NOP activation has been obtained from plant-cell suspension and isolated
      enzyme experiments. Using selected cytochrome P450 and peroxidase enzyme
      inhibitors in conjunction with Salmonella typhimurium strain TA98 and intact
      plant-cell activating systems as well as isolated horseradish peroxidase enzyme
      we have further investigated NOP activation by plant systems. The activation of
      NOP by both plant cells and by horseradish peroxidase was suppressed by the P450
      inhibitors methimazole and (+)-catechin and by the peroxidase inhibitors
      diethyldithiocarbamate and potassium cyanide, but was not suppressed by the P450
      inhibitors metyrapone and 7,8-benzoflavone. In addition, peroxidase enzymatic
      activity was measured and found to be inhibited by methimazole,
      diethyldithiocarbamate and potassium cyanide but not by (+)-catechin. The data
      strongly support the involvement of exogenous peroxidase in the plant activation
      of NOP, but point to a complex metabolic system that requires multistep
      processing before full mutagenic potential of the plant-activated component of
      NOP is expressed.

PMID- 7513797
TI  - An E. coli ada transgenic clone of Nicotiana tabacum var. Xanthi has increased
      sensitivity to the mutagenic action of alkylating agents, maleic hydrazide and
      gamma-rays.
AB  - Two transgenic clones X3 and X15 of Nicotiana tabacum var. Xanthi, heterozygous
      in two genes (a1 and a2) for chloroplast differentiation and transformed with the
      E. coli DNA repair gene ada cloned downstream from the 1' direction of the dual
      mas promoter, differed in the expression of the ada gene, in the number of copies
      of integrated T-DNA and in the response to the mutagenic action of alkylating and
      non-alkylating agents. The X3 genome contained four copies and the X15 genome one
      copy of T-DNA, nevertheless the expression of the ada gene, measured by the
      activity of O6-alkylguanine DNA alkyltransferase (ATase), was about six times
      higher in X15 than in X3. ATase activity in both clones was highest in extracts
      from callus whereas very low (X15) or no (X3) activity was detected in leaf
      extracts. This may explain the lack of difference between X15 and non-transformed
      tobacco (NTX) in the frequency of N-methyl-N-nitrosourea (MNU)-induced somatic
      mutations in leaves. In contrast, the frequency of somatic mutations in X3 was
      about 2-5 times higher than in NTX and X15 after the same doses of MNU, methyl
      methanesulfonate, maleic hydrazide and gamma-rays. Alteration of plant gene(s)
      essential in mutation pathway(s) by insertion of T-DNA or by somaclonal variation
      may explain the higher sensitivity of the X3 clone.

PMID- 7513800
TI  - Analysis of benzo[a]pyrene induced mutations by the use of Restriction-Site
      Mutation assays in aquatic species.
AB  - Larval and toadlet stages of the clawed toad Xenopus laevis were exposed to
      benzo[a]pyrene in aquatic media. Mutations were analysed in a variety of
      restriction enzyme recognition sequences of the adult alpha 1-globin gene.
      Mutations were detected in the BsiLi recognition site (CCTGG) at early sampling
      times (6 h) in larval stages and at 8-days sampling time in post-metamorphosis
      toadlets. The predominant mutation detected was a G-->T base transversion at the
      5th base of the CCTGG sequence. The data presented indicates that the Restriction
      Site Mutation methodology has considerable potential for development as a
      technique for monitoring the genotoxic potential of water-borne toxins.

PMID- 7513798
TI  - The nature of X-ray-induced mutations in mature sperm and spermatogonial cells of
      Drosophila melanogaster.
AB  - Mutations at four X-linked visible loci (yellow, white, vermilion and forked)
      induced by X-irradiation of mature sperm and spermatogonial cells were analysed
      genetically and cytogenetically. In addition, a fraction of the intragenic
      vermilion mutations was analysed molecularly. Males of two wild-type strains
      (Amherst M56i and Berlin-K) were used. A total of 332,651 chromosomes of
      irradiated mature sperm and 311,567 of irradiated spermatogonial cells were
      scored. The ratio of F1 female sterile, F2 male lethal and F2 male viable
      mutations in mature sperm and spermatogonial cells is very similar. The
      cytogenetic analysis shows equal fractions of multilocus deletions and
      translocations among the mutations recovered from both stages of spermatogenesis.
      These data strongly suggest that the spectrum of X-ray mutations is similar in
      mature sperm and spermatogonial cells, including multilocus deletions and
      chromosome rearrangements. The molecular analysis of a number of intragenic
      vermilion mutations showed the presence of three small deletions (1-10 bp), one
      insertion of two nucleotides and seven single nucleotide changes.

PMID- 7513799
TI  - The influence of large deletions on the mutation frequency induced by tritiated
      water and X-radiation in male Drosophila melanogaster post-meiotic germ cells.
AB  - Tritium beta radiation (3H beta-radiation) in the form of tritiated water was
      used to induce mutations at the alcohol dehydrogenase (Adh) locus in male
      Drosophila melanogaster post-meiotic germ cells. All 23 Adh null mutations were
      large deletions (> 20 kb), determined by genetic complementation and Southern
      blot analyses. 27 Adh null mutations have been induced by 100-kVp X-rays (Aaron,
      1979) and have been genetically and molecularly characterized (Ashburner et al.,
      1982; Chia et al., 1985; LoMonaco et al., 1987; Mahmoud et al., 1991). In
      contrast to 3H beta-radiation, 100-kVp X-rays induced a bimodal distribution of
      Adh null mutations, intragenic mutations, < or = 250 bp, and large deletions, >
      100 kb. A statistically significant difference was observed between the frequency
      of large deletions (23/23 or 1.0) induced by 3H beta-radiation and the frequency
      of large deletions (19/27 or 0.7) induced by 100-kVp X-rays. However, a
      statistical difference was not observed between the size distribution of the
      large deletions induced by 3H beta-radiation and X-rays. The relative deletion
      frequency (RDF) induced by 3H beta-radiation and 100-kVp X-rays was (1.0/0.7 =
      1.4). The relative biological effectiveness (RBE) of these two radiation sources
      was 1.4, determined from the ratio of the regression coefficients of the
      respective 3H beta-radiation and X-ray sex-linked recessive lethal (SLRL) dose
      response data. The large difference in size between the two classes of X-ray
      induced Adh null mutations and the increase in mutation frequency and deletion
      frequency for 3H beta-radiation with respect to X-rays may indicate that the
      relative deletion frequency (RDF) is the molecular biological basis for the
      increase in the RBE for radiation sources with a mean LET value < or = 10
      keV/microns.

PMID- 7513801
TI  - Induction of specific-locus and dominant lethal mutations in male mice by
      trophosphamide.
AB  - Trophosphamide induced dominant lethal and specific-locus mutations in
      spermatozoa and spermatids of mice. The induction pattern of specific-locus and
      dominant lethal mutations shows two maxima in the mating intervals 1-4 and 9-16
      days post treatment. The nature of induced mutations is suggested to be
      intergenic.

PMID- 7513802
TI  - Clastogenicity of trophosphamide in somatic and germinal cells of mice.
AB  - Trophosphamide, a chemotherapeutic agent structurally related to
      cyclophosphamide, was tested in the micronucleus and heritable translocation
      assays in mice. It induced a linear increase of micronuclei in polychromatic
      erythrocytes 24 h after treatment with 1, 5, 25 or 50 mg/kg. In spermatids and
      spermatozoa of mice heritable translocations were induced by 150 mg/kg with an
      average frequency of 6%. The doubling doses calculated for micronucleus induction
      and heritable translocation induction were 5.0 and 1.3 mg/kg, respectively. These
      values are in the same order of magnitude and suggest that somatic and germinal
      cells are similarly sensitive to the clastogenic action of trophosphamide.

PMID- 7513803
TI  - Isolation of micronuclei from mouse blood and fluorescence in situ hybridization
      with a mouse centromeric DNA probe.
AB  - Spontaneously existing and chemically induced micronuclei were isolated from
      mouse blood. 50 microliters of cardiac blood was diluted with PBS and
      centrifuged. After this, the cell pellet was subjected to hypotonic treatment,
      fixed with acetic acid-methanol (1:3), and the lysate was filtrated through a 2
      microns polycarbonate nucleopore membrane. Isolated micronuclei were air-dried on
      a glass slide and subjected to fluorescence in situ hybridization (FISH) using a
      mouse centromeric gamma satellite probe. Approximately half of the micronuclei
      isolated from vehicle control mice showed centromere signal(s). In these
      preliminary studies, the proportion of centromere-positive micronuclei was
      increased by treatment with spindle poisons (colchicine and vinblastine sulfate),
      decreased only slightly by 1-beta-D-arabinofuranosylcytosine, and was generally
      unaffected by mitomycin C.

PMID- 7513805
TI  - Metronidazole hprt mutation induction in sheep and the relationship with its
      elimination rate.
AB  - Gene mutations at the hprt locus were determined in peripheral blood lymphocytes
      from nine sheep treated with metronidazole (MZ) at therapeutic doses for
      amebiasis. Pharmacokinetic studies were also carried out, including the
      calculation of the apparent first-order elimination rate constant (K10) and the
      steady state concentration of MZ in plasma. Three sheep showed an increase of
      variant frequencies (Vf) at the hprt locus. A proportional relationship was found
      between the highest Vf and the highest steady state in plasma, and an inverse
      relationship between Vf and K10. The finding that the animals with the lowest
      elimination rates of MZ had increased gene mutations indicates that differences
      in pharmacokinetics constitute one potential mechanism of genotoxic
      susceptibility.

PMID- 7513804
TI  - Survival of UV-irradiated vaccinia virus in normal and xeroderma pigmentosum
      fibroblasts; evidence for repair of UV-damaged viral DNA.
AB  - Vaccinia virus replicates in the cytoplasm of cells from a large number of
      vertebrates and is independent of most or all cellular enzymes and factors needed
      for DNA replication and gene transcription. To investigate whether vaccinia virus
      is also independent of nucleotide excision-repair enzymes present in the nucleus,
      we have investigated the host-cell reactivation of UV-irradiated virus in normal
      human fibroblasts and fibroblasts from various xeroderma pigmentosum (XP)
      complementation groups (A, C, D, G and XP-variant). It was found that the
      survival of UV-damaged vaccinia virus is the same in the normal and all UV
      sensitive cell strains tested, suggesting it is independent of host-cell excision
      repair enzymes. This agrees with results of Lytle et al. (1972), but is in
      conflict with data from Zavadova (1971). The D37 of vaccinia virus survival is
      approximately 7 J/m2 in all cells tested, indicating that in normal cells
      vaccinia virus is very sensitive to ultraviolet light. We also found that
      cyclobutane pyrimidine dimers disappear from parental viral DNA strands,
      suggesting that vaccinia DNA is subject to some form of DNA repair. The
      implications of these results are discussed.

PMID- 7513807
TI  - Potentiation of bleomycin by the aminothiol WR-1065 in assays for chromosomal
      damage in G0 human lymphocytes.
AB  - The aminothiol radioprotector WR-1065 potentiates the induction of chromosome
      aberrations and micronuclei by the chemotherapy drug bleomycin in G(0) human
      lymphocytes. Potentiation by 5 mM WR-1065 was observed at bleomycin
      concentrations from 0.1 to 100 micrograms/ml in a 2-h treatment. The frequencies
      of micronuclei induced by bleomycin in the presence of WR-1065 reached that of
      500-fold higher concentrations of bleomycin alone. The potential therapeutic
      implications of these findings are discussed.

PMID- 7513808
TI  - Effects of treatment with mitoxantrone in combination with novobiocin, caffeine
      and ara-C on human lymphocytes in culture.
AB  - Many cytotoxic mechanisms have been proposed for the antineoplastic drug
      mitoxantrone (MXN), among them an interaction mediated by the cleavable DNA
      topoisomerase II complex. Cotreatment of human peripheral blood lymphocyte
      cultures from six donors with MXN (12 x 10(-6) micrograms/ml) and the inhibitors
      of DNA repair or synthesis, caffeine (10(-3) M) and ara-C (5 x 10(-6) M)
      administered as 30-min pulses did not potentiate the clastogenic effect of MXN on
      this biological system. However, treatment with MXN and novobiocin (10
      micrograms/ml), a non-specific DNA topoisomerase II inhibitor, led to a decrease
      in the chromosome aberrations induced by MXN in the G2 phase of the cell cycle.

PMID- 7513809
TI  - Frequencies of HPRT mutants and micronuclei in lymphocytes of cancer patients
      under chemotherapy: a prospective study.
AB  - Fifteen cancer patients, including 10 testicular carcinoma patients, were treated
      with several types of combination chemotherapy. Blood samples were collected
      before, during and after chemotherapy. Subsequently, lymphocytes were analyzed
      for frequencies of HPRT mutants (MF) and micronuclei (MNF). Significantly
      elevated MFs were detected in eight patients. Mean expression time (+/- SD) for
      mutations was 98 +/- 54 days (range: 42-172 days). In some patients, enhanced MFs
      persisted for a period of 430-490 days after cessation of chemotherapy. In five
      patients MNFs were increased 2-6-fold and the enhancement was fairly persistent.
      Ifosfamide and cyclophosphamide appeared to be the most mutagenic and clastogenic
      constituents of the chemotherapy, while evidence for adverse effects of
      adriamycin, 4-epi-adriamycin and bleomycin was equivocal. Results indicate that
      the clinical use of mutagenic drugs must be weighed against the risks of
      persistent genetic damage and secondary malignancies in cured patients and their
      potential offspring. Further studies are necessary to determine the true risks
      and incidence of such abnormalities following chemotherapy for curable forms of
      cancer.

PMID- 7513810
TI  - Analysis of restriction enzyme-induced chromosome aberrations in the interstitial
      telomeric repeat sequences of CHO and CHE cells by FISH.
AB  - The interstitial telomeric sequences have been suggested to be more susceptible
      to chromosome breakage and rejoining. In the present study, we tested this
      possibility by analysing the behavior of intra-chromosomal telomeric sequences in
      restriction enzyme-treated CHO and CHE cells. These cell lines show large blocks
      of internal telomeric repeats adjacent to the centromeric regions of the
      chromosomes. In CHO cells, (TTAGGG)n repeats are localised only near the
      centromeric regions of many of the chromosomes while in CHE cells the telomeric
      repeat sequences are found at both the terminal and centromeric regions of the
      chromosomes. In CHO cells, 26% of the total aberrations induced by AluI and 22%
      of those induced by HinfI were found to be involved with internal telomeric
      repeat sequences. In CHE cells, which possess telomeric repeats at both the
      terminal and interstitial regions, 39% of the aberrations induced by AluI and
      PvuII showed telomeric repeat signals. The proportion of acentric fragments with
      a telomeric repeat signal was higher in CHE than in CHO cells. Some of the
      damaged cells displayed an intense signal indicating the possible amplification
      of these repeats by telomerase. These results are in accordance with the
      suggestion that non-telomeric locations of telomeric repeat sequences are more
      prone to chromosome breakage and misrepair.

PMID- 7513806
TI  - The effect of various antioxidants and other modifying agents on oxygen-radical
      generated DNA damage in human lymphocytes in the COMET assay.
AB  - The effects of antioxidants and various other modifying agents on oxygen-radical
      generated DNA damage in human lymphocytes have been investigated using the COMET
      assay. Hydrogen peroxide (H2O2) and bleomycin (BLM) have produced clear dose
      related responses. In 38 independent experiments, there was consistency between
      the two donors used in the study for the negative and positive control data. The
      endogenous antioxidant catalase abolished effects with H2O2, but only slightly
      affected the response with BLM. Superoxide dismutase did not alter the response
      with H2O2 and only slightly affected BLM. The exogenous antioxidant vitamin C
      produced a clear dose-related response on its own. In combination with H2O2,
      there were small protective effects at low doses and exacerbating effects at high
      doses, but these were within the inter-experimental variability range. Vitamin E
      (trolox) produced no effects with either H2O2 or BLM, or on its own. Silymarin
      protected against the effect due to H2O2. Other modifying agents such as apo
      transferrin and deferoxamine mesylate produced a clear dose-related protection of
      effects due to BLM. This protection was less due to H2O2. In the presence of
      ferrous chloride, the effect due to BLM was exacerbated. In a small sample of 6
      smokers and 6 non-smokers, responses from smokers approached borderline
      significance (P = 0.054) by comparison with non-smokers. These observations would
      suggest that the COMET assay is a useful tool for examining issues related to
      oxidative stress in human lymphocytes.

PMID- 7513811
TI  - Induction of sister-chromatid exchanges by AluI, DNase I, benzon nuclease and
      bleomycin in Chinese hamster ovary (CHO) cells.
AB  - Various endonucleases (AluI, DNase I, benzon nuclease) and bleomycin induce
      sister-chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells. The
      frequencies of SCE are elevated in cells with chromosome-type aberrations, only
      slightly elevated in cells with chromatid exchanges, and in the control range in
      cells without chromosomal aberrations. These data indicate that SCE are produced
      when DNA breaks induced in G1 are either not repaired or misrepaired.

PMID- 7513812
TI  - Microgel electrophoresis assay (comet test) and SCE analysis in human lymphocytes
      from 100 normal subjects.
AB  - Microscopic examination of individual human lymphocytes embedded in agarose,
      subjected to electrophoresis and stained with a fluorescent DNA-binding dye,
      provides a novel way of measuring DNA damage as extent of migration of DNA
      fragments, mainly single-strand breaks. With this relatively simple method, DNA
      damage arising as a consequence of smoking, age and other factors was examined in
      peripheral human lymphocytes from 100 healthy individuals living in Pisa (Italy).
      The extent of DNA migration was found to be significantly increased by smoking.
      It is noteworthy that the effect of smoking was more significant in men than in
      women and that DNA migration was similar in the young and in the older people.
      SCE analysis did not reveal any significant effect of smoking, sex or age in the
      same population, suggesting a higher responsiveness of the comet test to DNA
      damaging agents.

PMID- 7513815
TI  - On the scoring of FISH-"painted" chromosome-type exchange aberrations.
AB  - The effectiveness of FISH painting for easy detection of radiation-induced
      chromosome aberrations lies, principally, in the fact that only part of any
      exchange event is highlighted. However, this partial detection imposes certain
      limitations when the technique is applied to fundamental studies with primary
      aberrations, particularly at higher doses, when Complex exchanges are present.
      Some of these limitations are discussed in this paper.

PMID- 7513814
TI  - Improved method for mutagenicity testing of gaseous compounds by using a gas
      sampling bag.
AB  - A simple and safety gas exposure method was developed using a gas sampling bag as
      an exposure vessel and a preparation vessel of diluted gas. The gas exposure
      conditions such as amount of S9 in the plate, volume of gas for the plate, amount
      of top agar, exposure period and exposure temperature were examined by
      mutagenicity testing of 1,3-butadiene using the gas sampling bag. Mutagenicity
      tests of 14 compounds and 1,3-butadiene on S. typhimurium TA98, TA100, TA1535 and
      TA1537, and E. coli WP2 uvrA were also examined by the developed gas exposure
      method. 1,3-Butadiene, propyne (methyl acetylene), monochlorodifluoromethane,
      ethylchloride, diborane and silane were mutagenic. 1-Butene, 2-butene, 2
      methylpropene, methyl vinyl ether, trichlorofluoromethane,
      dichlorodifluoromethane, 1,2-dichloro-1,1,2,2-tetrafluoroethane, 1,1
      difluoroethane and phosphine were not mutagenic on S. typhimurium TA98, TA100,
      TA1535 and TA1537, and E. coli WP2 uvrA with or without metabolic activation.
      These results were compatible with a previous report, and this developed method
      has the advantage that it can be tested easily and safely for combustible and
      self-combustible substances such as 1,3-butadiene and silane.

PMID- 7513813
TI  - Identification and chromosomal localization of a DNA fragment implicated in the
      partial correction of the Fanconi anemia group D cellular defect.
AB  - Fanconi anemia (FA) cells, complementation group D, which had been transfected
      with mouse genomic DNA were partially corrected for their mitomycin C (MMC)
      hypersensitivity. A genomic DNA fragment which complements the resistance of
      FA(D) cells to MMC close to normal level has been cloned; it has no correcting
      activity in FA group A cells. It contains two highly conserved regions between
      the mouse and human genome, which flank mouse repeated DNA. This DNA fragment
      detects a 3.6-4-kb mRNA transcript in human cells. Moreover this fragment maps to
      chromosome 11q23, a region of particular interest since several genes involved in
      the control of major cellular functions are located in this area. This DNA
      fragment may belong to a gene directly or indirectly involved in FA(D) function.

PMID- 7513816
TI  - 32P-postlabeling analysis of DNA adducts in tissues of rats exposed to coke-oven
      emissions.
AB  - Coke-oven workers are occupationally exposed to emissions containing relatively
      high levels of polycyclic aromatic hydrocarbons. Epidemiological studies suggest
      that this occupational exposure may lead to an increased risk of lung cancer. To
      evaluate a biologically effective exposure dose in human biomonitoring studies
      DNA carcinogen adduct analysis is frequently used. The most readily available
      source of cellular DNA in these studies is white blood cells (WBC). It is
      questionable whether WBC are an appropriate surrogate for target tissue cells. In
      this study an animal model was used to examine the relationship between DNA
      adduct levels in target tissues and WBC as a surrogate. Rats were exposed to
      emissions on the top of a coke-oven battery for 24 h during simultaneous sampling
      of the air for chemical analysis of polycyclic aromatic hydrocarbons. 32P
      Postlabeling analysis of DNA adducts in lung, heart, liver and WBC with the
      butanol enrichment procedure was conducted. DNA adduct profiles differ in target
      and non-target tissues and WBC analyzed. One major adduct was detected in the DNA
      from all tissues and WBC analyzed that exhibited the same chromatographic
      mobility as the predominant B(a)P adduct of the standard DNA sample. The highest
      levels of this adduct were observed in DNA from lung and heart--16.3 and 12.9
      adducts/10(9) nucleotides. The elevation compared to local control animals was
      6.8-fold for lung, 8.6-fold for heart, in WBC DNA 3-fold and in liver DNA only 2
      fold. In DNA samples from WBC and heart mainly this major adduct was observed. In
      liver DNA the other four distinct spots outside the diagonal zone (DRZ) and in
      lung two faster-migrating adducts inside the DRZ with higher intensities were
      detected. Evaluating total DNA adduct levels, almost the same extent of DNA
      damage in lung, heart and liver was observed (46.8, 37.7 and 46.2 adducts/10(9)
      nucleotides; WBC only 6.7 adducts/10(9) nucleotides). Our data showed that DNA
      injury in target tissue cells caused by exposure to coke-oven emissions may be
      more significant than expected only according to DNA adduct levels in WBC.

PMID- 7513818
TI  - Can we predict solar ultraviolet radiation as the causal event in human tumours
      by analysing the mutation spectra of the p53 gene?
AB  - The tumour suppressor gene, p53, has proved to be one of the genes most often
      modified in human cancers. These alterations consist mainly of point mutations
      located in the evolutionarily conserved sequences which render the protein
      inactive for its normal biological functions. In fact the p53 gene presents
      nearly 300 potential mutation sites whose analysis should enable the correlation
      of specific mutation spectra with different causal agents in cancer development.
      In this study we have analysed the mutation spectrum of the p53 gene in skin
      tumours from normal individuals and repair-deficient xeroderma pigmentosum (XP)
      patients in comparison with mutations found in internal cancers. Point mutations
      are mainly GC-->AT transitions in skin tumours (74% in non-XP, 87% in XP), and
      also to a lesser extent in internal tumours (47%) where, however, they are mainly
      located at CpG (63%) sequences probably due to the deamination of the unstable 5
      MeC. Moreover, mutations are targeted at py-py sequences in over 90% of skin
      tumours whereas the distribution of mutations in internal malignancies is
      proportional to the frequency of py-py sites (61%) and other sequences (39%) at
      mutable sites. Indeed, in XP skin tumours 100% of the mutations are targeted at
      py-py sequences and 55% of these are tandem CC-->TT transitions considered as a
      signature of UV-induced lesions. In skin tumours from normal individuals, 14% of
      the p53 mutations are double mutations and as in XP skin tumours all these are CC
      ->TT transitions. In contrast, internal tumours rarely contain tandem mutations
      (0.8%), and of these only 2/14 were CC-->TT transitions. Finally, nearly all
      (95%) of the mutations in XP are located on the non-transcribed strand while
      internal or non-XP skin tumours do not show this strand bias. Hence, the mutation
      spectrum analysed in XP skin tumours also demonstrates for the first time the
      existence of preferential repair in humans. In conclusion, the specificity of UV
      induced p53 mutation spectra in skin tumours shows that this gene is a
      particularly appropriate candidate for the correlation of mutation spectra with
      specific damaging agents.

PMID- 7513817
TI  - Temporal changes in the incidence of malignant melanoma: explanation from action
      spectra.
AB  - The incidence of malignant cutaneous melanoma has been increasing for more than
      50 years, and is now rising more rapidly than that of any other cancer. This
      increase is not explicable by changes in the physical environment, particularly
      by any observed increase in UVB radiation (290-320 nm). The distribution of
      melanomas on the body differs from the site distribution of nonmelanoma skin
      cancer (relatively many more melanomas occur on areas of the body not chronically
      exposed to sunlight, such as the back of the trunk in males, and the legs in
      females). This localization of melanoma, together with its epidemiology, suggest
      that a change in lifestyle has contributed to the fast-rising incidence in many
      countries. There is no convenient mammalian animal model for malignant melanoma.
      However, certain inter- and intra-specific hybrids of fish of the genus
      Xiphophorus are very sensitive to light-induced melanomas; we have used them to
      determine the wavelengths effective in melanoma induction. The action spectrum
      has a relatively very large component in the UVA region (320-400 nm) compared to
      human erythema. Hence, if the human and fish spectra were similar, the use of
      sunscreens that minimize erythema would have little effect in preventing the
      induction of melanoma, and if people using sunscreens expose themselves to
      sunlight for longer periods, they will be increasing dramatically their exposure
      to these melanoma-inducing wavelengths. Such considerations are sufficient to
      explain the rising incidence of malignant melanoma and its distribution on the
      body.

PMID- 7513820
TI  - Antimutagens as cancer chemopreventive agents in the diet.
AB  - It has been suggested that the use of antimutagens and anticarcinogens in
      everyday life will be the most effective procedure for preventing human cancer
      and genetic disease. There are several ways in which mutagenesis can be reduced
      or prevented. Chemicals which act to interfere with DNA repair or with mutagen
      metabolism can be effective antimutagens: however such compounds may also
      increase the probability of mutations by different chemicals or at different
      sites. In contrast, mutagen scavengers may be less prone to increase mutations by
      other chemicals. Selected examples illustrate that antimutagenic effects are
      often specific to certain classes of mutagen and/or certain test systems. Thus,
      if antimutagens are to have any impact on human disease, it is essential that
      they are specifically directed against the most common mutagens in daily life. On
      our current understanding, these are quite diverse in nature, so that
      combinations of antimutagens will probably be necessary. Two groups of mutagen
      scavengers (porphyrins and some types of dietary fibre) show some selectivity for
      large planar and hydrophobic types of carcinogen, which appear to be common in a
      normal Western diet. Increasing consumption of vitamins C and E, either through
      increased consumption of fruit and vegetables or through dietary supplementation
      might reduce formation of N-nitroso compounds, another common class of mutagens.
      Similarly, carotenoids and related compounds, already present at high quantities
      in some fruits and vegetables, have excellent antioxidant properties and should
      be able to counteract effects of endogenous metabolism and other events which
      generate oxidising species and free radicals. Still other types of antimutagen
      might be necessary to act against smaller non-planar carcinogens, but there is
      some question as to the importance of this type of carcinogen in a normal Western
      diet. It may be necessary to adjust the selection of antimutagens for different
      population groups, or as our understanding of mutagens in the diet develops
      further. Current assays for cancer chemoprevention in animals are unlikely to
      detect some important types of antimutagens, such as mutagen scavengers. A
      structured testing strategy is suggested, progressing from in vitro to in vivo
      antimutagenicity tests against a selected range of mutagens. Optimal use of
      antimutagens might be as a dietary supplement, additional to practical advice on
      increasing consumption of fruit and vegetables.

PMID- 7513819
TI  - Comparative two-stage cancer tests of ethylene oxide, N-(2-hydroxyethyl)-N
      nitrosourea and X-rays.
AB  - Mutagenicity tests have shown that the potencies of ethylene oxide and other
      alkylating agents relative to that of low-LET ionising radiation are
      approximately the same in different biological systems. In the present study this
      relationship, the radiation-dose equivalence ("rad-equivalence") of doses of
      genotoxic chemicals, was tested for the induction of tumours in skin and lung of
      mice using different initiation-promotion protocols. The initiators used were X
      rays, ethylene oxide and N-(2-hydroxyethyl)-N-nitrosourea (HOENU). This short
      term treatment was followed by treatment with the "promoters" 12-O
      tetradecanoylphorbol 13-acetate (TPA) and carbon tetrachloride. Unexpectedly, the
      animals treated with carbon tetrachloride did not show treatment-related liver
      tumours, but exhibited precocious death, mostly with lung tumours. According to
      estimates from in vitro tests the total in vivo dose from exposure to 400 ppm for
      4 x 5 h corresponds to 700 rad-equivalents. Although still with great statistical
      uncertainty, this ratio is supported by the observed time-dependent frequencies
      of animals with papillomas (in the TPA series) and lung tumours (in the carbon
      tetrachloride series). Animals treated with HOENU exhibited high incidences of
      tumours of both these types in approximate agreement with the higher rad
      equivalence of the treatments with this compound.

PMID- 7513821
TI  - Meeting report of the EC/US workshop on genetic risk assessment: "human genetic
      risks from exposure to chemicals, focusing on the feasibility of a parallelogram
      approach".
AB  - This workshop was the concept of Professor Frits Sobels who passed away on the
      6th of July 1993. The underlying idea of the Sobels' parallelogram approach is
      that an estimate (corrected by DNA-adduct dosimetry) of the genetic damage in
      human germ cells can be obtained by measuring a common endpoint in human and
      mouse somatic cells (such as gene mutation in lymphocytes) and in germ cells of
      mice, the desired target tissue inaccessible in humans. The main objective of the
      workshop was to identify the methodology, data requirements and mechanistic
      research to understand the human health impact of germ-cell mutagens. 4 chemicals
      were selected for review at the meeting: ethylene oxide, 1,3-butadiene,
      acrylamide and cyclophosphamide. The first 3 are important industrial chemicals
      with substantial use worldwide and, therefore, considerable potential human
      exposure. The 4th, cyclophosphamide, is a commonly used cancer chemotherapeutic
      agent. This first EC/US workshop on risk assessment was highly focused on the
      feasibility of the parallelogram concept to estimate potential germ-cell effects
      in humans. It represented an evaluation of current knowledge and the
      identification of future research needs for a more precise assessment of human
      genetic risks from exposure to mutagenic chemicals.

PMID- 7513822
TI  - X-ray-induced transcriptional activation of c-myc and XRCC1 genes in ataxia
      telangiectasia cells.
AB  - The transcriptional level of c-myc, c-jun and XRCC1 genes after X-irradiation was
      compared in human cells originating from subjects presumably with different DNA
      repair abilities. The mRNA amount of the beta-actin gene was used as an internal
      standard of transcription. The relative mRNA level of c-myc and XRCC1 genes was
      significantly increased 15 min after X-irradiation with doses of 2-8 Gy in ataxia
      telangiectasia (AT) cells (AT5BIVA and TAT2SF), in contrast to little change in
      xeroderma pigmentosum (XP2OS(SV) and XP2YO(SV)) and normal cells (WI38VA13 and
      GM0637). The increased mRNA level of the XRCC1 gene in AT5BIVA and of the c-myc
      and XRCC1 genes in TAT2SF cells was maintained for up to 8 h after X-irradiation
      with 2 Gy. For the c-jun mRNA level after X-irradiation with 2-8 Gy, no
      significant change was observed in all cell lines tested. These results indicate
      that AT cells show a high transcriptional response of certain genes in response
      to X-irradiation, and suggest that the transcriptional activation of c-myc and
      XRCC1 genes after X-irradiation may be related to the hyper-radiosensitivity of
      AT cells.

PMID- 7513823
TI  - Transcription and nucleotide excision repair--reflections, considerations and
      recent biochemical insights.
AB  - Recent years have witnessed considerable progress in the definition of the
      preferential repair of actively transcribed genes. Equally impressive progress
      has been achieved in our understanding of the genetic and biochemical complexity
      of the DNA-repair process called nucleotide excision repair (NER). Most recently
      studies in several laboratories have yielded observations which provide insights
      about how the processes of transcription and NER may be linked in prokaryotic and
      eukaryotic cells.

PMID- 7513824
TI  - Enzyme-dependent pausing during in vitro replication of O4-methylthymine in a
      defined oligonucleotide sequence.
AB  - We had previously reported that an oligonucleotide containing a site-specifically
      incorporated O4-methylthymine (m4T) was replicated under kinetic conditions by
      the Klenow fragment of E. coli DNA polymerase I (Kf) (Dosanjh et al., 1993).
      Using other polymerases for complete replication, but with limiting enzyme, a
      pause site before the m4T was observed. In order to investigate whether such a
      pause could be due to enzyme dissociation or stalling, trapping experiments were
      designed to aid in differentiating the two mechanisms. Rather than the generally
      used heparin or sheared DNA trap, these experiments utilized as the acceptor the
      same oligonucleotide containing unmodified thymine. It was observed that, under
      enzyme-limiting conditions, the nature of the enzyme played a major role in
      replication of m4T. With a running start, Kf and calf-thymus polymerase alpha
      primase allowed replication beyond the m4T, while Sequenase and T7 showed a
      strong pause site at the base before m4T. When the oligonucleotide trap was added
      after different times of replication, it was found that Sequenase remained bound
      to the template-primer, regardless of whether T or m4T was present. In contrast,
      Kf dissociated and re-associated rapidly. Thus, m4T appears to be a strong
      replication block when using limiting amounts of a highly processive enzyme such
      as Sequenase or T7. This may imply that such enzymes discriminate against forming
      a poor basepair but remain bound to the primer-template or become inactivated.

PMID- 7513825
TI  - Molecular dosimetry of 7-alkyl- and O6-alkylguanine in DNA by electrochemical
      detection.
AB  - A methodology is described for the quantitation of 7-alkyl- and O6-alkylguanine
      in DNA isolated from experimental animals exposed to alkylating agents. Following
      purification, the DNA is hydrolysed under acid conditions after which 7-alkyl-
      and O6-alkylguanine are separated from unmodified bases by HPLC using a strong
      cation exchange column. The fractions containing the methylated purines are
      subsequently analyzed by HPLC using a reverse phase column coupled to an
      electrochemical detector (amperometric). This method allows the detection of 10
      20 fmoles 7-alkyl- and O6-alkylguanine, when pure markers are analyzed. In
      practice, the detection limit is 0.5 adducts per 10(6) nucleotides for the
      methylated and 1 adduct per 10(6) nucleotides for the ethylated form of 7-alkyl-
      and O6-alkylguanine using 25 micrograms DNA.

PMID- 7513827
TI  - Structure-activity relationships within various series of p-phenylenediamine
      derivatives.
AB  - The mutagenicity of 20 p-phenylenediamine derivatives has been investigated in
      Salmonella typhimurium. Tests were performed in the presence and in the absence
      of Aroclor 1254-induced liver S9 fractions derived from male Wistar rats. Among
      five series of compounds tested, nitro-p-phenylenediamines with substituents at
      the C6 position (4-amino-3-nitro-6-methylaniline; 4-amino-3-nitro-6
      methoxyaniline; 4-amino-3-nitro-6-fluoroaniline; 4-amino-3-nitro-6-chloroaniline;
      and 4-amino-3-nitro-isopropylaniline) were the most mutagenic. In all cases, the
      compounds were less mutagenic in the absence of S9 than in its presence, but
      three of the five compounds (the methoxy, fluoro, and chloro derivatives) were
      still mutagenic without the metabolic activation system. In contrast to the
      mutagenicity of the C6-substituted compounds, the mutagenicity of analogues with
      substituents on the C5 position (4-amino-3-nitro-5-beta-hydroxypropylaniline; 4
      amino-3-nitro-5-isopropylaniline; 4-amino-3-nitro-5-methylaniline; and 4-amino-3
      nitro-5-beta-hydroxyethylaniline) was abolished or reduced. A dramatic reduction
      in mutagenic activity was also achieved when two methyl groups, instead of one,
      were added to 4-amino-3-nitroaniline. For example, 4-amino-3-nitro-5,6
      dimethylaniline and 4-amino-3-nitro-2,5-dimethylaniline were only weakly
      mutagenic, and 4-amino-3-nitro-2,6-dimethylaniline as 4-amino-2-6
      dimethylaniline; 4-amino-5,6-dimethylaniline; was nonmutagenic. Monocyclic
      compounds such as 4-amino-2,6-dimethylaniline; 4-amino-5,6-dimethylaniline; 4
      amino-2-methoxy-3,5-dimethylaniline, and 4-amino-2,3,5,6-tetramethylaniline were
      all nonmutagenic in Salmonella typhimurium. The compound 4-amino-2,5
      dimethylaniline was weakly mutagenic or nonmutagenic, whereas 4-amino-2,5
      dimethoxyaniline was mutagenic. It appears that the mutagenic activity or
      inactivity of these compounds depends on both the chemical groups present and
      their positions in the molecule. In this context, it seems that the presence of
      the NO2 group and the nature of the substituent groups at the C5 and C6 positions
      on the benzene ring are crucial factors in determining the mutagenicity of these
      compounds.

PMID- 7513826
TI  - Chromosome aberrations: persistence of alkylation damage and modulation by O6
      alkylguanine-DNA alkyltransferase.
AB  - Alkylating agents produce a spectrum of DNA lesions alkylated at different sites
      on the molecule. These lesions differ in their propensities to cause effects such
      as cytotoxicity, mutations and sister-chromatid exchanges. We have used our
      observations that some methylating agents produce increasing levels of chromosome
      aberrations (abs) through successive cell cycles in Chinese hamster ovary cells,
      but not in normal human cells, to begin a study of which alkylated products are
      most likely to lead to chromosome abs, and in particular which adducts persist in
      DNA and cause abs after the first cell cycle. We previously observed increasing
      yields of abs with successive cell cycles in CHO-WBL cells treated with dimethyl
      nitrosamine (DMN), e.g., at 10 mM DMN, 8.8% cells with abs at first metaphase
      (M1) and 26.0% at third metaphase (M3) after treatment. Here we tested 4
      methylating agents and their ethyl analogs in CHO cells, normal human fibroblasts
      (L136), and human lymphocytes. We sampled cells at several times after treating
      for 3 h (CHO and lymphocytes) or 4.5 h (L136). S9 metabolic activation was used
      for DMN and diethyl nitrosamine. BrdUrd labeling was used to identify cells in
      M1, M2 and M3. The methylating agents were more potent aberration (ab) inducers
      than ethylating agents, on a molar basis. In CHO cells, yields of abs were
      maintained or increased through up to 3 cell cycles after treatment with DMN,
      methyl methanesulfonate, methyl nitrosourea and 1-methyl-3-nitro-1
      nitrosoguanidine (MNNG). With ethylating agents the ab yields in CHO cells were
      similar or lower in second and third cycles. In contrast, there was no evidence
      for persistence of lesions leading to abs in either human cell type; ab yields
      were markedly decreased with subsequent cell cycles for all agents. Normal human
      cells are proficient in repair of alkylation at the O6 site of guanine by O6
      alkylguanine-DNA alkyltransferase (AGT), whereas CHO cells lack AGT activity. To
      explore the role of repair by AGT on the lesions involved in production of abs,
      we studied L136 cells, with and without O6-benzylguanine (BZG), a specific
      inhibitor of AGT. With MNNG, inhibition of AGT resulted in higher ab yield and
      production of abs through later cell cycles, so that human fibroblasts now
      behaved similarly to CHO cells. Preliminary data from the reciprocal experiment
      in CHO cells engineered to express high levels of AGT revealed a greatly
      decreased ab response to MNNG. In addition, the low ab yields observed were
      similar through later cycles or increased only slightly.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7513828
TI  - Formation and persistence of DNA adducts in pouch skin fibroblasts and liver
      tissue of rats exposed in vivo to the monofunctional alkylating agents N-methyl-N
      nitrosourea or N-ethyl-N-nitrosourea.
AB  - Base substitutions and frameshifts induced by genotoxic agents are considered to
      result mainly from incomplete repair and incorrect replication of modified
      nucleotides in DNA. In this study, induction and persistence of O6-alkyl- and 7
      alkylguanine adducts were determined by reverse phase HPLC and electrochemical
      detection in DNA of pouch skin fibroblasts and liver tissue of rats exposed in
      vivo to the monofunctional alkylating agents N-methyl-N-nitrosourea (MNU) and N
      ethyl-N-nitrosourea (ENU). Although an exposure dependent increase in the level
      of adducts was found for both chemicals, a much lower frequency of both O6
      alkylguanine and 7-alkylguanine was detected after ENU treatment than after MNU
      treatment, indicating that MNU is much more reactive with DNA than ENU. The
      persistence of O6-alkyl- and 7-alkylguanine was studied for up to 48 h at
      exposure levels of 60 mg/kg for MNU and 100 mg/kg for ENU. A time-dependent
      decline in the levels of both adducts was observed, but w6-alkylguanine was more
      rapidly lost than 7-alkylguanine in both pouch skin fibroblasts and liver.
      Furthermore, DNA adducts were faster lost from liver than from pouch skin
      fibroblasts. The loss of O6-alkylguanine adducts is probably mediated by the
      action of O6-alkylguanine-DNA alkyltransferase (AGT) in the target tissues since
      AGT activity was detectable in protein extracts of pouch skin fibroblasts and
      liver from unexposed rats and from exposed rats, 48 h but not 1 h after MNU and
      ENU treatment. AGT activity recovered faster in liver tissue than in pouch skin
      fibroblasts, and after ENU exposure an induction of AGT activity was observed in
      the liver but not in pouch skin fibroblasts. The difference in the level of O6
      alkylguanine in DNA of pouch skin fibroblasts introduced upon exposure to MNU and
      ENU may explain the molecular nature of most base pair changes observed
      previously in spectra of hprt mutants induced in these cells in vivo. The
      frequency of O6-methylguanine upon MNU exposure remains relatively high with time
      and these adducts most likely cause GC to AT transitions. In the case of ENU, O6
      ethylguanine was detected at very low frequencies resulting in a low contribution
      of GC to AT transitions. Rather, the ENU spectrum is dominated by base pair
      changes at AT base pairs.

PMID- 7513830
TI  - [Palliative treatment of pancreatic carcinoma. Comparison between 2 successive
      observation periods].
AB  - Explorative laparotomies and palliative surgery for pancreatic carcinoma have
      been reduced due to improved diagnostic tools, the spread of laparoscopic
      techniques and the growing use of external biliary drainage and endoprostheses.
      By comparing two successive observation periods the authors point out that, owing
      to the good results obtained, mini-invasive surgery is more frequently used in
      the management of obstructive jaundice than biliodigestive surgical derivations.
      Of these, hepatico-jejunostomy is preferable to duodenal anastomosis due to the
      latter's frequent involvement by the primary tumour. The authors also consider it
      inappropriate to increase operative morbidity through the systematic association
      of gastroenteric with biliodigestive derivation, except in cases of symptomatic
      or radiologically or endoscopically ascertained duodenal stenosis and when the
      objective finding of visceral involvement leads to the supposition of its
      imminent obliteration. The indications for surgical splannicectomy have also been
      reduced with the spread of percutaneous alcoholization of the celiac plexy in
      cases which resist analgesic treatment using a parenteral route.

PMID- 7513831
TI  - [A technical suggestion for laboratory tests in cases of rape].
AB  - The paper suggests completing the clinical tests carried out in cases of rape by
      collecting material not only from the fornix of the vagina but also from the
      cervical canal using cotton-wool buds, and examining any spermatozoa adhering to
      the cotton filaments by staining with Baecchi's method. Alternatively, the paper
      suggests carrying out these tests in anticipation of their possible use as
      forensic evidence if requested by the court.

PMID- 7513829
TI  - Effects of kainic acid, quisqualic acid, and their antagonist, pCB-PzDA, on rat
      electrocorticograms and monoamine metabolite levels in rat striatum.
AB  - The action of kainic acid (KA), quisqualic acid (QA), and 1-(4-chlorobenzoyl)
      piperazine-2,3-dicarboxylic acid (pCB-PzDA) was investigated in the central
      nervous system of male Sprague Dawley rats. Intracerebroventricularly injected KA
      and QA (100 nmol) induced spike discharges, and pCB-PzDA (100 nmol) suppressed
      electrocorticograms for one hour. pCB-PzDA enhanced the KA-induced spike
      discharges and inhibited those induced by QA. 2,3-Di-hydroxyphenylacetic
      acid(DOPAC) and homovanillic acid (HVA) levels were increased transiently by 10
      nmol and continuously by 100 nmol of KA. KA dose-dependently increased 5
      hydroxyindoleacetic acid (5-HIAA) levels 2 hours after administration. While 10
      nmol of QA slightly increased the HVA level, 100 nmol of QA significantly
      increased DOPAC, HVA, and 5-HIAA levels. DOPAC and HVA levels were increased by
      100 nmol of pCB-PzDA, although this agent inhibited KA-induced increases in
      DOPAC, HVA, and 5-HIAA levels. On the other hand, while pCB-PzDA first inhibited
      QA-induced increases in DOPAC, HVA and 5-HIAA levels for one hour, DOPAC and HVA
      levels thereafter increased additively. These findings suggest that pCB-PzDA may
      act not only as a NMDA antagonist, but that it may also act directly on
      dopaminergic neurons.

PMID- 7513833
TI  - Sciatic axotomy compromises axonal transport of transganglionic tracer BSI-B4
      from the soma to the central terminals of C fibre afferents.
AB  - The C afferent specific lectin BSI-B4 was used to examine the effects of sciatic
      axotomy on axonal transport by the C afferent subpopulation. From about 4 days
      after sciatic nerve lesion, BSI-B4 injected into the peripheral nerve is
      transported only as far as the neuronal cell bodies in the dorsal root ganglion.
      The previous demonstrations of A beta afferent terminal sprouting into lamina II,
      and the atrophy of lamina II terminals, in response to sciatic lesions may be
      related to the inability of C afferents to maintain transganglionic transport.

PMID- 7513832
TI  - Should HCV RNA detection affect the isolation policy in dialysis units?

PMID- 7513834
TI  - Co-localization of nitric oxide synthase and NGF receptor in neurons in the
      medial septal and diagonal band nuclei of the rat.
AB  - The relationship of neurons that express nitric oxide synthase type I (NOS-I),
      the synthetic enzyme of the free radical nitric oxide (NO), with cells that
      contain the low affinity p75 nerve growth factor receptor (NGFr) was examined in
      the basal forebrain region of the rat using double immunohistofluorescence. NOS
      and NGFr were found to be co-localized in a neuronal population that displayed a
      selective distribution. Double immunopositive neurons were evident in the medial
      septum and in rostral levels of the diagonal band nuclei where the vast majority
      (more than 80%) of NOS-immunoreactive cells were also NGFr-positive; the two cell
      populations were separate at more caudal levels of the basal forebrain. These
      findings support the chemical heterogeneity of septal and basal forebrain neurons
      which contain NGFr and indicate that in the rat a subset of neurons of the septum
      diagonal band complex may release NO.

PMID- 7513835
TI  - Demonstration of retinal cells expressing messenger RNAs of the c-kit receptor
      and its ligand.
AB  - We found cells expressing c-kit receptor and its ligand (Sl factor, SLF) in the
      retina of rats and mice. c-kit messenger RNA (mRNA) was detected in a limited
      number of cells in the inner nuclear layer of rats and mice by in situ
      hybridization. The c-kit-expressing cells were assumed to be a subpopulation of
      the amacrine cells on the basis of their size and distribution pattern. c-kit
      protein-containing cells were demonstrated in the mouse retina by using ACK2
      monoclonal antibody against the extracellular domain of the mouse c-kit receptor.
      The c-kit protein was detected in cell bodies and processes of the presumed
      amacrine cells. Hybridization signals for SLF mRNA were observed in the retinal
      ganglion cells. The results suggest that the c-kit receptor and its ligand may
      play some roles in the formation of junctions between the amacrine and retinal
      ganglion cells.

PMID- 7513836
TI  - Postnatal ontogeny of the neurotrophin receptors trk and trkB mRNA in rat sensory
      and sympathetic ganglia.
AB  - Using reverse transcription followed by polymerase chain reaction, we examined
      the expression of mRNA for the tyrosine kinase receptors trk and trkB in rat
      sensory and sympathetic ganglia during postnatal development. While the levels of
      both trk and trkB mRNA in the dorsal root ganglia (DRG) decreased two-fold, they
      increased by seven and two times, respectively, in superior cervical ganglia. The
      developmentally regulated and tissue-specific expression of trk and trkB genes
      suggest that peripheral ganglia differ in their responsiveness to neurotrophins
      in neonatal and adult rats. We found that the temporal pattern of trk expression
      in DRG neurons correlates with the observed age-dependent ability of nerve growth
      factor to induce the biosynthesis of the neuropeptide substance P.

PMID- 7513837
TI  - Endothelin-1 enhances capsaicin-induced peptide release and cGMP accumulation in
      cultures of rat sensory neurons.
AB  - Because endothelin-1 (ET-1) may be a neuromodulator in sensory systems, we
      examined whether this peptide could alter release of substance P (SP) and
      calcitonin gene-related peptide (CGRP) from isolated sensory neurons. Although ET
      1 had minimal actions on spontaneous neuropeptide release, pretreating cultures
      with 500 nM resulted in a 50% augmentation of SP and CGRP release evoked by 50 nM
      capsaicin. Moreover, 2000 nM ET-1 enhanced capsaicin-evoked release of CGRP two
      fold. In an analogous manner, ET-1 alone did not alter intracellular cGMP
      content, but enhanced the increase in cGMP caused by 50 nM capsaicin.
      Intracellular cAMP was not altered by capsaicin and/or ET-1. These data suggest
      that ET-1 may play a role in modulation of peptide release from primary afferent
      neurons.

PMID- 7513838
TI  - Substance P receptors on human astrocytoma cells are linked to glycogen
      breakdown.
AB  - In this study we report that substance P stimulated [3H]glycogen breakdown and
      elevation of intracellular Ca2+ concentration in the human astrocytoma cell line
      UC-11MG. Both effects were dose dependent, and completely blocked by CP-96,345
      suggesting the involvement of an NK1 receptor. Our previous studies indicated
      that norepinephrine and histamine stimulate glycogenolysis via cAMP and Ca2+
      respectively. Combined stimulation with substance P and norepinephrine or
      histamine resulted in additive effects suggesting that there is no interaction
      between these neurotransmitters in regulating glycogenolysis in these cells.
      These results confirm that UC-11MG cells are a useful model system to investigate
      the functional role of neurotransmitter receptors in astroglial cells.

PMID- 7513839
TI  - Substance P-, neurokinin A-, calcitonin gene-related peptide- and neuropeptide Y
      like immunoreactivity (-LI) in rat knee joint synovial fluid during acute
      monoarthritis is not correlated with concentrations of neuropeptide-LI in
      cerebrospinal fluid and plasma.
AB  - In a recent study we have shown a bilateral release of substance P (SP)-,
      neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y
      (NPY)-like immunoreactivity (-LI) in rat synovial fluid during acute
      monoarthritis. In order to elucidate the mechanisms underlying these phenomena,
      we examined the correlation between neuropeptide-LI in rat cerebrospinal fluid
      (CSF) and synovial fluid and between plasma and synovial fluid following the
      intra-articular injection of equal volumes (0.05 ml) of either Freund's adjuvans,
      carrageenan 2%, substance P 10(-5) M or human recombinant interleukin-1 alpha.
      Control rats were given saline intra-articularly. CSF, plasma and synovial fluid
      from the knee joints were obtained at 2, 6 and 24 h after injection and were
      analysed by specific radioimmunoassays. The intra-articular injection of pro
      inflammatory substances induced changes in neuropeptide-LI in synovial fluid, CSF
      and plasma. However, there was no correlation between neuropeptide-LI in synovial
      fluid and plasma or between synovial fluid and CSF. The results of the present
      study does not support the hypothesis that the bilateral changes in neuropeptide
      LI in synovial fluid were due to a release of neuropeptides from the inflamed
      joint into the systemic circulation. However, in carrageenan induced inflammation
      there was a tendency towards a correlation in SP-LI between CSF and synovial
      fluid suggesting that central neurogenic mechanisms should be studied in order to
      explain the bilateral changes seen.

PMID- 7513840
TI  - An intermediate conductance calcium-activated potassium channel in rat visceral
      sensory afferent neurons.
AB  - Whole-cell and single channel recordings were used to characterize an
      intermediate conductance calcium-activated potassium (KCa) channel in sensory
      neurons of the nodose ganglion. From a -80 mV holding potential, the total
      outward current in these neurons was increased when extracellular calcium was
      raised from 0.02 to 5 mM. This calcium-evoked outward current was not blocked by
      either charybdotoxin (50 nM) or apamine (40 nM). In the inside-out patch
      configuration, the current-voltage relationship for this channel was linear
      between -60 and +60 mV in symmetrical 145 mM potassium aspartate (KAsp) and
      possessed a conductance of approximately 60 picosiemens (pS). Increasing [Ca2+]i
      from 0.01 microM to 1.0 microM markedly increased the cumulative open probability
      of this channel and the effect of increasing [Ca2+]i on these channels was not
      voltage dependent. In the outside-out patch configuration, neither
      tetraethylammonioum (TEA), (1 mM), apamine (40 nM) or charybdotoxin (ChTx) (50
      nM) had any effect on the activity of this channel. These results provide new
      evidence for the existence of pharmacologically distinct intermediate conductance
      KCa channel in sensory afferent neurons.

PMID- 7513841
TI  - L-type voltage-sensitive calcium channel antagonists block heterosynaptic long
      term depression in the dentate gyrus of anaesthetized rats.
AB  - We examined the role of dihydropyridine-sensitive Ca2+ channels in long-term
      potentiation (LTP) and long-term depression (LTD) in the dentate gyrus of
      pentobarbital-anaesthetized rats. Intrahippocampal infusions (1.0 microliter) of
      nimodipine (20 mM) and nifedipine (20 mM), two antagonists of L-type voltage
      sensitive calcium channels (VSCC), 60 min prior to medial perforant path
      tetanization, completely blocked the appearance of LTD in the lateral perforant
      path, without significantly affecting the simultaneous induction of medial path
      LTP. Heterosynaptic LTD was not significantly different from control animals
      following infusions of the L-type calcium channel agonist BAY-K8644 (1 mM). These
      results suggest that L-type VSCC activity is necessary for the induction of
      heterosynaptic LTD in the dentate gyrus in vivo.

PMID- 7513842
TI  - Extrinsic denervation increases NADPH diaphorase staining in myenteric nerves of
      guinea pig ileum.
AB  - The number of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)
      positive cells in the myenteric plexus increased 1 week after surgical extrinsic
      denervation of a loop of guinea pig ileum. NADPH-d staining in submucosal ganglia
      and vasoactive intestinal polypeptide immunoreactivity in submucosal and
      myenteric ganglia were not affected by denervation. Similar data were obtained
      after systemic capsaicin, but not 6-hydroxy-dopamine treatment, suggesting that
      loss of primary afferents increases NADPH-d staining. Increases in NADPH-d may be
      part of an adaptive process allowing normal gut function after loss of extrinsic
      nerves.

PMID- 7513843
TI  - AMPA/kainate receptor-mediated damage to NADPH-diaphorase-containing neurons is
      Ca2+ dependent.
AB  - While exposure times of several hours or more are needed for AMPA or kainate to
      induce widespread cortical neurodegeneration, the small subset of cortical
      neurons that contain high concentrations of the enzyme, NADPH-diaphorase (NADPH
      d(+) neurons) were destroyed by brief (15-30 min) exposures. AMPA or kainate
      induced degeneration of NADPH-d(+) neurons was decreased by removal of
      extracellular Ca2+ and increased by augmentation of extracellular Ca2+. More than
      90% of NADPH-d(+) neurons exhibited kainate-activated Co2+ uptake, suggesting
      that they possess Ca(2+)-permeable AMPA/kainate receptor-gated channels. The
      heightened vulnerability of NADPH-d(+) neurons to AMPA or kainate toxicity may
      reflect rapid Ca2+ entry through these Ca(2+)-permeable channels.

PMID- 7513844
TI  - Clinical efficacy of recombinant human granulocyte colony-stimulating factor in
      patients with head and neck cancer.
AB  - Recombinant human granulocyte colony-stimulating factor (rG-CSF) was used for the
      amelioration of neutropenia caused by cisplatin-based chemotherapy in head and
      neck cancer patients. For a dose-finding study of rG-CSF, 11 patients, who had
      levels of absolute neutrophil counts below 500/mm3 in peripheral blood, were
      administered rG-CSF subcutaneously at a dose of 1 or 2 micrograms/kg for 5 days.
      A 'useful' rate in 1 and 2 micrograms/kg was obtained in 71.4 and 100% of
      patients, respectively. In 6 patients, the clinical utility of rG-CSF at a dosage
      of 2 micrograms/kg from the day after chemotherapy for 10 consecutive days was
      observed. The percentage of 'very useful' evaluations was 83.3% (5/6). No side
      effects or abnormal laboratory findings were observed in any patients after
      administration of rG-CSF.

PMID- 7513845
TI  - Identification and assessment of nucleolar organizer regions (NORs)--technical
      problems.
AB  - NORs are the loops of DNA containing ribosomal genes which are associated with
      non-histonic argyrophilic proteins. It permits their identification by using
      specific argyrophilic staining. NORs are visualized in light microscopy as AgNOR
      dots or argyrophilic NOR dots. Neoplastic and proliferative cells show
      differences with respect to the number, area and distribution of AgNOR dots.
      Major difficulties in the analysis of AgNOR dots are caused by technical problems
      associated with staining and fixation of the tissue. In our study we found that
      correct fixation of nucleolar proteins associated with AgNORs was a decisive
      factor in correct interpretation of the results.

PMID- 7513846
TI  - Ki-1-positive anaplastic large cell lymphoma: a morphologic and immunologic study
      of 14 cases.
AB  - This report analysed the phenotype of fourteen cases of Ki-1-positive anaplastic
      large cell lymphoma, recently described high-grade malignant lymphoma. In 12
      cases the neoplasm involved lymph nodes, two patients presented with primary
      extra-lymphoid involvement (stomach, larynx), whereas secondary involvement of
      the skin was observed in one patient. Immunohistochemical study revealed B-cell
      phenotype in seven cases; three cases presented T-cell specific markers; in three
      cases we found antigens characteristic for both lymphoid lineages and one case
      presented null phenotype. Ki-1 (CD30) antigen was found in every of 14 cases, and
      LeuM1 (CD15) antigen was not expressed in any of studied cases. In two cases we
      revealed the expression of cytokeratins (CAM 5,2). The foregoing results confirm
      heterogeneity of this neoplasm and suggest careful interpretation of the results
      of morphologic and immunohistochemical findings in any pleomorphic and anaplastic
      tumour.

PMID- 7513848
TI  - A complete cDNA sequence for ribosomal protein S6 of Xenopus laevis.

PMID- 7513847
TI  - Codon reading scheme in Mycoplasma pneumoniae revealed by the analysis of the
      complete set of tRNA genes.
AB  - The 33 genes encoding the complete set of tRNA species in Mycoplasma pneumoniae
      have been cloned and sequenced. They are organized into 5 clusters in addition to
      9 single genes. No redundant gene was found, indicating that 33 tRNAs correspond
      to 32 different anticodons and decode all 62 codons used in this organism. There
      is only one single tRNA for each of the Ala, Leu, Pro, and Val family boxes.
      Therefore, a simplified decoding system resembling that recently described for
      Mycoplasma capricolum (1) has to also exist in M.pneumoniae. However, analysis of
      the anticodon set and codon usage revealed features characteristic of the latter:
      (i) there is no obvious preference toward AT rich synonymous codons, (ii) CGG
      codons are assigned for arginine and are translated by tRNA Arg(UCG), and (iii)
      CNN or GNN anticodons are encountered in the Ser, Thr, Arg, and Gly family boxes.
      We thus propose that this codon-anticodon recognition pattern has emerged in the
      'M.pneumoniae cluster' under a genomic economization strategy but without the
      influence of AT pressure.

PMID- 7513850
TI  - Pacemaker failure induced by radiotherapy.
AB  - It is well documented that radiation therapy can have significant transitory and
      permanent effects on the function of cardiac pacemakers. In this study 18
      multiprogrammable pacemakers were tested to establish any pattern by which these
      pacemakers are affected. The results confirm previous predictions on how
      pacemakers are damaged. The damage could be divided essentially into three types:
      (1) temporary change to interference or safety mode pacing lasting for the
      duration of the irradiation only; (2) change to interference mode pacing--from
      which recovery may occur after reprogramming the pacemaker; and (3) severe
      damage; in this case the pacemaker stops generating pulses. Recovery from this
      may occur a long time after the end of the treatment, but this recovery is mostly
      incomplete and the pacemaker cannot be used reliably thereafter. Therefore it is
      essential that patients with implanted pacemakers undergoing radiation therapy,
      should be monitored closely during the course of the treatment and for a few
      weeks thereafter.

PMID- 7513849
TI  - Quality assurance in cardiac electrophysiology and pacing: a brief synopsis.

PMID- 7513851
TI  - DDI pacing: indications, expectations, and follow-up.
AB  - The DDI mode of pacing that permits noncompetitive atrioventricular sequential
      bradycardia support was chosen in 65 of 480 (14%) patients selected for dual
      chamber pacing between February 1985 and March 1990. All patients were implanted
      with Pacesetter 283 or 285 pulse generators and programmed to DDI. The
      indications for pacing were sick sinus syndrome (n = 52), combined sinus node
      dysfunction and AV block (n = 13). Forty-two of these patients had a history of
      paroxysmal atrial arrhythmias. All patients received passive fixation atrial and
      ventricular leads. Follow-up thereafter was performed predischarge, and at 6
      weeks, 3 and 6 months after discharge. The duration of follow-up ranged from 1-61
      months (mean 31 months). Fifty-four of 65 (83%) patients chosen for DDI remain
      programmed in the DDI mode. Three patients were reprogrammed to VVI and eight to
      DDD. During the course of follow-up, six patients presented with effective VVI
      pacing with consistent ventriculoatrial conduction that was appropriately sensed
      by the atrial circuit with atrial output inhibition. A further four patients
      presented with "functional undersensing" due to ventricular blanking period (VBP)
      characteristics in these pulse generators and in this mode. Functional
      undersensing was eliminated in all but one patient by reprogramming the VBP to 13
      msec with no subsequent episodes of provoked crosstalk inhibition. Effective VVI
      pacing was observed in patients with AV block during times of sinus
      acceleration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513852
TI  - A pilot study: defibrillation thresholds in dogs are similar with isoflurane,
      halothane, and pentobarbital.
AB  - The objective of this pilot study was to determine if three common anesthetic
      drugs have differing effects on the measurement of defibrillation thresholds
      (DFT) in dogs. The drugs compared were pentobarbital, isoflurane, and halothane.
      We used six dogs, which were surgically instrumented, in a chronic study design.
      Each dog had two internal defibrillation patches placed on its heart, which were
      used to deliver the defibrillation energy. DFT was determined while each dog was
      anesthetized under each of the listed drugs in a crossover design. This pilot
      study suggests that differences in DFT due to the anesthetic drugs is not
      significant in studies with low numbers of animals (halothane 14.5 +/- 1.0,
      isoflurane 14.2 +/- 1.0, pentobarbital 12.8 +/- 1.0; P = NS; mean +/- SE). The
      variation in DFT between individual animals is much larger than the difference in
      DFT due to the drugs.

PMID- 7513853
TI  - Programmed ventricular stimulation using tandem versus simple sequential
      protocols.
AB  - The objective was to determine whether two commonly used ventricular stimulation
      protocols, one more complex than the other, produced concordant results. If such
      were the case, the simpler protocol would streamline activities in clinical
      electrophysiology laboratories. BACKGROUND: Two programmed ventricular
      stimulation protocols were compared. (1) With the tandem method, the first
      extrastimulus (S2) is moved stepwise to the effective refractory period and then
      moved out 50 msec; the second extrastimulus (S3) is then decremented until it
      fails to capture; S2 and S3 are then decremented in a semialternating (tandem)
      fashion so that both continue to capture. When S2 reaches the refractory period +
      10 msec and S3 fails to capture, S3 is then moved out 50 msec, and S4 is
      decremented as described for S3. (2) With the simple sequential method, the first
      extrastimulus (S2) is decremented stepwise to the refractory period, and then
      moved out 10 msec to assure capture; S3 is then similarly decremented to the
      refractory period and then moved out 10 msec; and S4 is then similarly
      decremented. METHODS: This was a prospective, randomized, crossover, consecutive
      series study. Both protocols were tested in each patient on the same day in
      randomized order. RESULTS: There were 84 matched studies. Fifty-six patients
      provided data from baseline electrophysiological studies, and 28 of these
      provided additional data during drug trials. There was a 93% concordance between
      the two methods, including the primary outcomes of inducibility of clinical
      arrhythmias, inducibility of nonclinical arrhythmias, and noninducibility (P <
      0.001). Discordances were few and evenly distributed between the two protocols (P
      = NS). Results were similar for baseline studies and drug trials. The simple
      sequential method required less time to perform (P < or = 0.01). CONCLUSIONS:
      Tandem and simple sequential protocols provide concordant results. No advantage
      could be demonstrated for the more complex tandem method.

PMID- 7513854
TI  - Significance of supraventricular tachyarrhythmias in patients with implanted
      pacing cardioverter defibrillators.
AB  - Eighty-six patients were treated with an implantable cardioverter defibrillator
      (ICD) because of sustained ventricular tachycardia (VT) or ventricular
      fibrillation (VF). In 27 patients an epicardial system was used, in 59 patients a
      transvenous system with a subcutaneous patch electrode was implanted. During a
      mean follow-up time of 17 +/- 9 months, inappropriate activations of the ICD due
      to supraventricular tachycardia were documented by Holter monitoring in 14
      patients (16%). In 8 patients paroxysmal atrial fibrillation (AF), in 2 patients
      chronic AF, in 1 patient atrial flutter, and in 3 patients sinus tachycardia
      triggered antitachycardia pacing functions (12 patients) or internal
      defibrillation (2 patients). In 3 patients (5%) VT was induced by inappropriate
      antitachycardia pacing. In an additional 18 patients (21%) inappropriate
      activation of antitachycardia functions due to atrial tachyarrhythmias were
      suspected based on telemetry readouts or the patient's history. Inappropriate
      activation of ICD therapy triggered by intermittent supraventricular
      tachyarrhythmias is common. Further improvements of detection algorithms for
      supraventricular tachycardia are required in future device generations.

PMID- 7513855
TI  - Signal-averaged ECG parameters in cardiac normals using Frank lead system and
      Fourier transform filter and gender specific differences: a multicenter study.
AB  - There is only limited data on normal reference values for signal-averaged
      electrocardiograms (SAECGs) using Frank leads and fast Fourier transform filter
      (FFT). Furthermore, the influence of gender on reference values and their
      relation to body characteristics was only the subject of a few studies on small
      series of normals. One hundred eighty-five cardiac normals (85 women and 100 men)
      were examined in this multicenter study. The obtained SAECG values (mean +/-
      standard deviation) are as follows: filtered QRS duration (FQRSD) = 108.6 +/- 7.5
      msec; low amplitude signal duration < 40 microV (LASD) = 30.4 +/- 8.4 msec; and
      root mean square voltage in the terminal 40 msec (RMSV) = 43.5 +/- 20.6 microV.
      Between men and women, significant differences were found in FQRSD (111.7 +/- 6.5
      vs 105.0 +/- 7.0 msec, P < 0.001) and in RMSV (38.6 +/- 17.4 vs 49.4 +/- 22.7
      microV, P < 0.001). No difference was observed for LASD. After normalizing the
      three SAECG parameters for body characteristics, FQRSD normalized for height was
      the only variable where gender differences were eliminated. For FQRSD and LASD
      the 90th percentile and for RMSV the 10th percentile are proposed as cut-off
      values. Only for the 90th percentile of FQRSD a clear difference between men and
      women was observed. The following gender specific normal values for SAECG, at 40
      Hz high pass filtering, using Frank leads and an FFT filter are proposed: for
      males, FQRSD < 122 msec; for females, FQRSD < 115 msec; for both genders, LASD <
      41 msec and RMSV > 20 microV.

PMID- 7513856
TI  - A selective, non-ischemic, non-pharmacological left ventricular failure animal
      model.
AB  - Selective left ventricular failure was induced in 13 acute anesthetized, closed
      chest dogs ranging in weight from 18-26 kg. Failure was induced by passing a
      single, high intensity pulse of current from a defibrillator connected to a left
      ventricular catheter electrode and a left chest electrode. The intensity of the
      myocardial damaging shock was related to the predicted current required for
      transventricular defibrillation, based on heart weight. Thermodilution cardiac
      output, left ventricular pressure, impedance stroke volume, the cardiac
      electrogram, and lead II ECG were recorded, along with the pressure impedance
      (volume) loop, which is a measure of stroke work. It was found that the cardiac
      output decreased with increasing current intensity. Immediately following the
      high current shock, cardiac output, and stroke work decreased. In some animals,
      with a moderate intensity shock, there was a transient increase in cardiac
      output, followed by a decrease. In the five animals that were monitored
      continuously for 4 hours, the average percent reduction in cardiac output at this
      time was 42.5% for an average current overdose ratio of 5.39. The energy setting
      on the defibrillator to obtain this range of reduction in cardiac output was 175
      350 joules. The method described herein is easily applied to the closed chest
      animal and will allow evaluation of the pumping capabilities of cardiac
      augmentation techniques, such as dynamic cardio-myoplasty and the skeletal muscle
      ventricle.

PMID- 7513857
TI  - Apparent extension of the atrioventricular interval due to sensor-based algorithm
      against supraventricular tachyarrhythmias.
AB  - Rapid ventricular tracking response to supraventricular tachyarrhythmia is one
      major limitation to DDD pacing. In a DDDR pacemaker, sensor-based algorithms have
      been used to control these arrhythmias. These include the use of an interim rate
      limit (conditional ventricular tracking limit) or a separate maximum tracking and
      sensor rate limits (discrepant upper rate). These algorithms limit inappropriate
      ventricular pacing rate during tracking of pathological supraventricular
      tachyarrhythmia and atrial flutter by Wenckebach-like prolongation of the AV
      interval. We observed that this may cause an unexpected extension of the AV
      interval in patients with high atrial rate and intact AV nodal conduction. This
      was due to P wave rate above the conditional ventricular tracking limit or
      maximum tracking limit, but AV paced interval prolongation was avoided by the
      occurrence of intrinsic conduction, albeit at an AV interval longer than the
      programmed AV interval. This might appear as failure of ventricular pacing on the
      ECG. This phenomenon is a modified form of "upper rate" behavior occurring in the
      AV interval, and should be recognized as a normal behavior rather than pacemaker
      malfunction.

PMID- 7513858
TI  - Detection of atrial fusion systole in patients with dual chamber pacemakers by 24
      hour esophagus ECG.
AB  - We performed ambulatory 24-hour esophagus ECG in nine patients with dual chamber
      pacemakers suspect of transient arrhythmias in order to achieve correct and
      reliable P wave identification during daily life activities. In all patients
      episodes were observed with varying atrial artifact to left atrial depolarization
      sequences. These episodes probably reflected presence of atrial fusion systole,
      an ECG phenomenon which should be taken into account when analyzing ambulatory
      esophagus ECG. Thus, the ambulatory esophagus ECG revealed its ability to detect
      spontaneous atrial depolarization in the presence of pacemaker artifact in
      patients with DDD(R) pacemakers.

PMID- 7513859
TI  - Modification of atrioventricular conduction using a combined laser-electrode
      catheter.
AB  - Ablation of the AV junction is an accepted technique for the management of
      selected supraventricular tachyarrhythmias. Radiofrequency ablation appears to be
      safe and effective for AV junction ablation in most patients, but the need for
      firm tissue contact may make it less effective for ventricular tachycardia and
      certain ectopic/atrial tachycardias. Laser energy can also be delivered through a
      catheter, and thus it may be an attractive alternative energy source for
      ablation. A new laser-electrode catheter was developed for modification of
      conduction through the AV node as a model for ablation of an arrhythmia
      substrate. A window for delivery of continuous-wave Nd:YAG laser energy was
      placed between the two electrodes of a bipolar electrode catheter. In vitro
      studies using a matrix of power versus time were performed to determine the
      energy that would create lesions of the appropriate size in vivo. Using this
      information, advanced AV block was successfully created in 16 of 17 dogs (94%)
      with the laser-electrode catheter. Advanced AV block was successfully created in
      all four dogs in the chronic study, and it persisted for 1-24 weeks of follow-up
      until sacrifice of the animals. Histologic examination demonstrated discrete
      thermal damage at the AV junction with no instances of septal perforation in the
      acute studies or progressive necrosis in chronically maintained dogs. Advanced AV
      block may be produced consistently and safely in dogs using a combined laser
      electrode catheter.

PMID- 7513860
TI  - Electrophysiological testing of sinus node function: diagnostic and prognostic
      application-including updated information from sinus node electrograms.
AB  - Sinus node function, including automaticity, conduction, and refractoriness, can
      be studied in the human electrophysiology laboratory. This review details the
      current methods used for such studies and discusses their clinical value. Of
      special emphasis in this article is the role of sinus node electrography in the
      clinical laboratory. Included also is an update of the data relating the duration
      of sinus node depolarization as measure on sinus node electrograms to other
      parameters that assess sinus node function as well as data supporting the direct
      relationship between the duration of the sinus node depolarization as the
      severity of sinus node dysfunction.

PMID- 7513861
TI  - Meet me on the Internet.

PMID- 7513862
TI  - The changing health care environment: can innovation in the treatment of
      cardiovascular disease be preserved?

PMID- 7513863
TI  - DDD pacemaker syndrome and atrial conduction time.

PMID- 7513864
TI  - Sustained left ventricular tachycardia terminated by dipyridamole: cyclic AMP
      mediated triggered activity as a possible mechanism.
AB  - Sustained VT in two patients was terminated by intravenous administration of
      dipyridamole, an adenosine transport inhibitor. VT was induced by rapid atrial or
      ventricular pacing, isoproterenol, or dibutyryl cyclic AMP infusion, or exercise.
      VT also was aborted by adenosine triphosphate or acetylcholine injection, or by
      vagal stimulation. VT was terminated or prevented by verapamil or propranolol. In
      addition, arrhythmias were prevented by oral administration of dipyridamole.
      These results suggest that VT is due to cyclic AMP-mediated triggered activity
      and that inhibition by dipyridamole may be due to a reduction in the
      intracellular concentration of cyclic AMP.

PMID- 7513865
TI  - Coincident idiopathic left ventricular tachycardia and atrioventricular nodal
      reentrant tachycardia: control by radiofrequency catheter ablation of the slow
      atrioventricular nodal pathway.
AB  - A healthy 37-year-old male presented with a history of frequent palpitations and
      sustained wide QRS complex tachycardia with a right bundle branch block and left
      axis morphology. Serial electrophysiological studies revealed two inducible
      tachycardias, which were shown to represent atrioventricular nodal reentrant
      tachycardia and idiopathic left ventricular tachycardia. Transformation from one
      tachycardia to the other occurred spontaneously as well as following atrial or
      ventricular pacing. Radiofrequency catheter ablation of the slow atrioventricular
      nodal pathway resulted in cure of atrioventricular nodal reentrant tachycardia
      and the prevention of spontaneous recurrence of ventricular tachycardia,
      suggesting a role of atrioventricular nodal reentrant tachycardia in triggering
      the clinical episodes of ventricular tachycardia. The patient has remained
      asymptomatic without antiarrhythmic therapy for 8 months.

PMID- 7513867
TI  - Ventricular Arrhythmias: State of the Art. Proceedings of an international
      workshop. Gottingen, Germany, June 11-12, 1993.

PMID- 7513866
TI  - Development of an aortic valve mass after radiofrequency catheter ablation.

PMID- 7513869
TI  - Exercise ECG: prognostic implications of exercise induced arrhythmias.

PMID- 7513868
TI  - Risk stratification after myocardial infarction.

PMID- 7513870
TI  - Insights into the pathogenesis of sudden cardiac death from analysis of circadian
      fluctuations of potential triggering factors.
AB  - Sudden cardiac death continues to be a poorly understood event in terms of its
      underlying pathophysiological mechanisms. The observation of a circadian
      variability in the incidence of this catastrophic event with a prominent peak in
      the early morning hours provides an opportunity to study triggering factors that
      may play a causative role in the genesis of sudden cardiac death. As reviewed in
      this article, there is convincing evidence that transient disturbances in
      autonomic tone and the resulting consequences may predispose the heart to
      increased electrical vulnerability. This evidence is based for instance on
      circadian fluctuations of spontaneous ventricular ectopic activity and transient
      ischemia, which may serve as trigger factors for the genesis of sustained
      ventricular tachyarrhythmias. Analysis of heart rate variability provides further
      evidence of reduced vagal and elevated sympathetic tone during the morning hours
      particularly in patients with compromised left ventricular function. Diurnal
      variations in ventricular repolarization as indicated by QT interval changes in
      the surface ECG also support the concept of triggering factors in the genesis of
      sudden cardiac death. Therapeutic measures aiming at a reduction in sympathetic
      input to the heart have been successful in preventing ventricular fibrillation
      and thus indicate the importance of unbalanced sympathetic tone in patients prone
      to sudden cardiac death.

PMID- 7513871
TI  - Baroreflex sensitivity: methods, mechanisms, and prognostic value.
AB  - A large bulk of data collected over the last 25 years links reflex autonomic
      activation during acute myocardial ischemia with risk of developing lethal
      arrhythmias. Specifically, evidence obtained in an experimental preparation in
      chronically infarcted dogs supported the concept that sympathetic hyperactivity
      enhances likelihood for ventricular tachyarrhythmias, vagal activation exerts
      protective effects. Based on this knowledge, it was first proposed by our group
      that analysis of autonomic control of heart rate could provide information
      relevant to risk stratification in post-myocardial infarction individuals. Among
      several possibilities, baroreflex sensitivity was evaluated by correlating blood
      pressure rise induced by bolus injections of phenylephrine with the consequent
      beat to beat R-R interval lengthening. Experimental studies involving direct
      recordings from single neural vagal fibers directed to the heart documented that
      baroreflex sensitivity closely reproduces cardiac vagal activity. In a large
      group of conscious dogs it was shown that a depressed baroreflex sensitivity was
      highly predictive of the risk for ventricular, fibrillation during acute
      myocardial ischemia. The clinical prognostic value of baroreflex sensitivity has
      already been confirmed in pilot studies conducted by different groups of
      investigators. Overall, the phenylephrine test has been performed in several
      hundred patients with no reports of side effects. An ongoing multicenter study,
      the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) is aimed to
      definitively assess the predictive value of baroreflex sensitivity and heart rate
      variability in patients with a prior myocardial infarction. While the enrollment
      is still ongoing, this study has already provided an important methodological
      information about the possibility of using non invasive technique to record blood
      pressure by means of FINAPRES, to evaluate baroreflex sensitivity. Comparison
      among 142 tests performed with simultaneous recording from an intraarterial line
      and from FINAPRES indicated a strong correlation (r = 0.9) between the two
      methods. ATRAMI is expected to close the enrollment in the near future. To data,
      baroreflex sensitivity appears to be a safe and non-invasive test likely to
      provide meaningful information on autonomic balance and consequently on risk
      profile of patients with a prior myocardial infarction.

PMID- 7513872
TI  - Spectral analysis of the high resolution ECG: current concepts and future
      directions.

PMID- 7513873
TI  - Programmed ventricular stimulation: uses and limitations.

PMID- 7513874
TI  - Empiric therapy with beta-blockers.
AB  - The only class of drugs with significant effects on ventricular fibrillation and
      sudden death in humans is that of beta-blockers. The exact mechanisms for these
      prophylactic effects are not known but may be related to both antiischemic or
      antiarrhythmic influences. It seems reasonable to suggest that one should use a
      beta-blocker with proven effect on total mortality and sudden cardiac death after
      myocardial infarction as prophylaxis. Therefore, propranolol, timolol, or
      metoprolol, should be instituted in order to improve prognosis when there are no
      contraindications. In addition to possible effects on survival one would also
      expect to reduce the risk for new ischemic events with angina or reinfarction. In
      contrast, class I antiarrhythmic agents are useful for symptomatic ventricular
      arrhythmias but there is no proof for any effect on ventricular fibrillation and
      sudden cardiac death.

PMID- 7513875
TI  - Value and risk of class I and III antiarrhythmic drugs.

PMID- 7513877
TI  - Mechanisms of defibrillation for monophasic and biphasic waveforms.

PMID- 7513876
TI  - Results of Holter ECG guided therapy for ventricular arrhythmias: the ESVEM
      trial.
AB  - The Electrophysiological Study Versus Electrocardiographic Monitoring (ESVEM)
      trial randomized 486 patients with spontaneous sustained ventricular tachycardia
      (VT), ventricular fibrillation (VF) or unmonitored syncope, who manifested
      reproducibly inducible sustained ventricular arrhythmias by provocative
      stimulation and 10 or more premature ventricular contractions per hour on Holter
      monitoring, to two groups treated with pharmacotherapy guided by suppression of
      stimulation-inducible VT/VF or suppression of spontaneous or exercise induced
      ventricular arrhythmias. There was no difference over four years of follow-up in
      the rates of recurrence of arrhythmias, arrhythmic mortality, cardiac mortality,
      or mortality from any cause between the two groups of patients but more patients
      (77%) received pharmacotherapy in the group treated on the basis of suppression
      of spontaneous arrhythmias than the group treated on the basis of
      electrophysiological study. In this trial, rates of recurrence of arrhythmias
      were higher (37% at one year and 66% at four years) than generally reported, but
      cardiac and arrhythmia mortality were comparable or lower than generally
      reported. Of the seven agents tested, six were sodium channel blockers
      (imipramine, mexiletine, procainamide, propafenone, pirmenol, and quinidine) and
      the other was sotalol. Sotalol had a significantly higher rate of efficacy
      predictions by EPS (35%) than the others (15%) and a comparable rate by Holter
      monitor. Sotalol was significantly more efficacious in preventing recurrences,
      arrhythmic mortality, cardiac mortality, and total mortality than the other
      agents and it was better tolerated. Probability of successful long term therapy
      with a sodium channel blocker tested by electrophysiological study was low (5% at
      one year).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513878
TI  - Acute efficacy and chronic follow-up of patients with non-thoracotomy third
      generation implantable defibrillators.
AB  - Non-thoracotomy implantation of implantable cardioverter defibrillators (ICDs)
      has simplified the process of device insertion, promising to decrease associated
      procedural complications while providing sudden death protection at least equal
      to epicardial systems. This study presents the acute and chronic results of 110
      patients who underwent attempted non-thoracotomy ICD implantation with the
      Medtronic Transvene lead system and PCD model 7217 or 7219. Of the 110 patients
      attempted, 100 (91%) had the system successfully implanted without the need for
      an epicardial patch. One patient died 1 week postoperatively of septic shock
      related to the implantation (0.9% perioperative mortality). During follow-up of
      16 +/- 11 months, 45% of the patients had an event detected as ventricular
      tachycardia; 26% of these detections were felt clinically to be due to
      supraventricular rhythms. Of the remainder, 87% were successfully treated with
      the first VT therapy, and 98% were terminated by the final therapy; 66% of the
      patients had at least one episode of ventricular fibrillation, of which 5% were
      felt to be inappropriate detections; 85% of the appropriate episodes were
      successfully treated with the first VF therapy, and all were converted by the
      final therapy. Total mortality at 6, 12, and 24 months was 3%, 11%, and 19%
      respectively. Only one patient had sudden cardiac death, occurring at 13 months
      postimplant. Overall, the non-thoracotomy lead system for this ICD displayed
      infrequent implant complications and proved to be reliable at terminating
      arrhythmias and maintaining a low rate of sudden cardiac death in this high risk
      population.

PMID- 7513879
TI  - Role of antitachycardia pacing in patients with third generation cardioverter
      defibrillators.
AB  - The most effective antitachycardia pacing (ATP) mode is still a matter of debate.
      Randomized prospective testing of 3 different ATP modes was performed in 65
      patients (pts) prior to and after cardioverter defibrillator implantation (Ventak
      PRx 36 pts, Cadence V 100 29 pts). All 3 ATP modes included 4 stimulation
      attempts with 4-7 adaptive scanning burst pulses. Adaptive burst coupling
      interval was 75% in mode A, 81% in mode B and 69% in mode C. Autodecremental
      scanning within bursts was 8 msec in all, decremental scanning between bursts was
      8 msec in modes B and C. Each ATP mode had to be tested 3 times; all 3 ATP modes
      were randomly applied to each pt. During preoperative testing 91 of 133 VT
      episodes (68%) could be terminated by ATP. Termination was achieved in 68% with
      mode A, 68% with mode B and 73% with mode C. During predischarge testing, 251 VTs
      were induced and ATP was successful in 147 VTs (59%). Termination rate was 56%
      with mode A, 68% with mode B and 50% with mode C. During the mean follow-up of 12
      months, 2301 arrhythmia episodes (AE) occurred. ATP was performed in 2097 AE
      (91%) and successful in 1920 AE (92%). Acceleration of VT occurred in 65 AE (3%)
      and unsuccessful ATP was observed in 112 AE (5%). It is concluded that ATP in
      general is highly effective in pts with sustained VT. None of the tested ATP
      modes, however, proved to be superior to the other.

PMID- 7513880
TI  - Value of prophylactic implantable cardioverter defibrillator therapy.

PMID- 7513881
TI  - Magnetocardiographic localization of the origin of ventricular ectopic beats.
AB  - Magnetocardiographic mapping opens new perspectives for three-dimensional
      localization of cardiac electrical activation. Using a 37-channel SQUID
      magnetometer equipment with high shielding, the origin of abnormal ventricular
      activation was investigated in 18 patients with Wolff-Parkinson-White syndrome
      prior to catheter ablation and in 5 of 31 patients with coronary artery disease
      having a sufficient number of monomorphic ventricular extrasystoles to enable
      evaluation. In all WPW-patients, the site of the earliest delta-wave activation
      was projected onto the AV-valve plane in accordance with the MR images. The
      result of magnetocardiographic localization was then compared to the site of
      successful catheter ablation determined by digital imaging processing. After
      optimization of the algorithms, both sites were in the various planes at the
      following distance from each other: X-plane: 0.8 +/- 0.9 cm, Y-plane: 1.1 +/- 1.0
      cm and Z-plane: 1.5 +/- 1.0 cm. In three-dimensional projection, the mean
      difference in space between both positions was calculated to be 2.1 +/- 1.7 cm.
      After this validation ventricular premature beats were localized in another group
      of patients. In 4 of 5 patients their origin was found at the border of infarct
      areas. In each case, the progression of the ventricular activation could be
      pursued. The detected structure of the magnetic field distribution of the VBP's
      exhibited a stable bipolar pattern, which is comparable to that of ventricular
      tachycardia, and its algorithms may be used to localize the origin of ventricular
      tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513883
TI  - Catheter ablation of ventricular tachycardia occurring late after myocardial
      infarction: a point-of-view.
AB  - Ventricular tachycardia can be controlled by radiofrequency or chemical ablation
      of the site of origin of the arrhythmia. However, these techniques are far from
      being accepted as routine treatment for this problem. This article describes the
      theoretical and practical background of catheter ablation of ventricular
      tachycardia occurring late after myocardial infarction.

PMID- 7513884
TI  - Management of patients after catheter ablation of ventricular tachycardia.
AB  - The management of patients after catheter ablation of ventricular tachycardia is
      not well defined. In this article we summarize recently published results and
      report our own experience. Factors influencing the clinical outcome of these
      patients and methods to identify patients with an increased risk of recurrence of
      ventricular tachycardia are discussed. Furthermore, a review is given on current
      concomitant therapeutic tools including antiarrhythmic drugs and the implantation
      of an automatic cardioverter defibrillator.

PMID- 7513885
TI  - Direct, electrophysiologically guided operations for malignant ischemic
      ventricular tachycardia.

PMID- 7513882
TI  - In vivo ventricular lesion growth in radiofrequency catheter ablation.
AB  - While radiofrequency catheter ablation has proved highly effective in the
      treatment of various supraventricular tachyarrhythmias, results in the treatment
      of ventricular tachycardia invite improvement. Knowledge of lesion growth in vivo
      might improve understanding of this discrepancy. So far only information from in
      vitro and in vivo studies using a small 2 mm tip electrode is available. Growth
      of ventricular radiofrequency lesions created with a 4 mm ablation electrode was
      studied in 11 closed-chest dogs. Endocardial ablations were performed at 31 left
      and 15 right ventricular sites at a power setting of 25 Watts and 5, 10, 20, 30
      or 60 seconds pulse duration. Macroscopic and histopathologic lesion examination
      were performed after one week survival. Mean lesion volume increased from 52 mm3
      after 5 seconds pulse duration to a maximum 388 mm3 and approximately 7 mm depth
      after 30 seconds. Lesions were prolate spheroid in form, with a sparing of
      subendocardial myocardium and maximum lesion diameter at some millimeters depth.
      Results indicate that catheter positioning at no more than 7 mm from the target
      is required for successful ablation. Due to lesion geometry, subendocardial
      targets demand even more exact catheter positioning, while subepicardial
      substrates may not be ammenable to ablation if ventricular wall thickness exceeds
      7 mm at the ablation site. Repeated pulses at adjacent sites may be required for
      ablation of extended arrhythmogenic areas. Volume at 5 seconds was only
      approximately 15% of mature lesions. Therefore, the use of a short 'test pulse'
      after careful mapping may be useful to pinpoint the most appropriate site for
      ablation in discrete pathways.

PMID- 7513886
TI  - The effect of coronary bypass graft surgery for the prevention of sudden cardiac
      death: recurrent episodes after ICD implantation and review of literature.
AB  - Sudden cardiac death (SCD) accounts for at least 50% of the mortality of patients
      with ischemic heart failure. Ventricular arrhythmias are responsible for most
      cases of sudden cardiac death. There is some evidence that coronary artery bypass
      graft (CABG) surgery may reduce the incidence of recurrent episodes of SCD by
      prevention of myocardial ischemia. To test the hypothesis that CABG surgery is
      effective in the prevention of SCD, we compared the recordings of implantable
      cardioverter defibrillators (ICD) in patients who underwent ICD implantation
      alone (n = 64) or ICD implantation and concomitant CABG surgery respectively (n =
      11). All patients had experienced out of hospital cardiac arrest. ICD recordings
      were obtained every 3 months and the number of recurrent episodes of ventricular
      tachycardia (VT) for each time period was noted. Three months following ICD
      implantation patients in the surgically treated group had an average of one
      episode of VT per patient as compared to 2.7 episodes in the nonsurgical group.
      This difference was observed during the following months as well. However, at no
      time (up to 18 months of follow-up) this difference reached statistical
      significance. There were no deaths in the surgically treated group. Although we
      could not demonstrate a statistical significant difference between the two
      groups, there was a tendency in the surgically treated group to have less
      episodes of recurrent VT than in the medically treated group. We, therefore,
      conclude that survivors of SCD presenting with multivessel coronary artery
      disease (CAD) should undergo coronary artery bypass grafting to prevent
      myocardial ischemia as the triggering event for lethal ventricular arrhythmias.

PMID- 7513887
TI  - Management of patients with ventricular tachyarrhythmias: does an optimal therapy
      exist?

PMID- 7513888
TI  - Co-amplification of the cystic fibrosis delta F508 mutation with the HLA DQA1
      sequence in single cell PCR: implications for improved assessment of polar bodies
      and blastomeres in preimplantation diagnosis.
AB  - We have developed a heminested PCR (polymerase chain reaction) method, performed
      on single cells, for the analysis of the most common cystic fibrosis (CF)
      mutation (delta F508). As a quality control, the polymorphic exon 2 of the HLA
      DQA1 locus was co-amplified from the same cell. With a non-radioactive reverse
      dot-blot assay, the genotype of these two loci could be determined. Experiments
      on 98 single fibroblasts, heterozygous for the CFTR and the DQA1 locus, showed
      that amplification of either locus could be obtained in 97 per cent of the cases,
      but only 90 per cent showed heterozygosity for CF, 75 per cent showed
      heterozygosity for DQA1, and 74 per cent showed heterozygosity for both CF and
      DQA1. Contaminations detected only after DQA1 typing occurred in 3 per cent of
      our samples. Error rate calculations based on our experimental PCR data indicate
      that single blastomere diagnosis would lead to unacceptable errors, i.e., an
      affected fetus, in less than 1 per cent of the cases. The risk of undetected
      crossing-over or the dubious results that crossing-over could generate, would
      make isolated polar body diagnosis at the present time very difficult. The
      combined approach of PCR on polar bodies followed by confirmation of the
      diagnosis on blastomeres, however, should give a solid base for preimplantation
      diagnosis of monogenic disorders.

PMID- 7513889
TI  - Asymptomatic carrier of two CFTR mutations: consequences for prenatal diagnosis?
AB  - The cystic fibrosis (CF) gene has been observed to have the highest frequency of
      mutations in the Caucasian population. Prenatal diagnosis can now be performed
      with a high degree of accuracy since the identification of most of the gene's
      mutations, as well as the characterization of intragenic markers. However, the
      observation of a distribution of clinical phenotypes increases the need to
      identify a mild phenotype and avoid false-negative diagnosis. By screening most
      of the exons of the CFTR gene, we showed that a supposed obligate carrier of CF
      was in fact an asymptomatic affected woman.

PMID- 7513890
TI  - Recurrent low second-trimester hCG.

PMID- 7513891
TI  - Effects of an advanced surgical nursing module on clinical practice.
AB  - 1. Innovation and changes in practice can be developed through continuing
      education. 2. By adapting appropriate change strategies, theories learned in
      class can be applied in practice. 3. Excellence in quality can be achieved by all
      qualified nurses by applying theory to practice.

PMID- 7513893
TI  - Bullfight: the aficion.
AB  - Bullfighting, as a spectacle, provides a special frame for projections,
      externalizations, and identifications. The central appeal of bullfighting is
      sadistic gratification, which seems to be of a mostly parricidal nature. The
      public experiences intense ambivalence toward the protagonists of the fight, who
      exert attraction for the id as well as for the superego. The existence of
      intrasystemic conflicts is pointed out. The history of bullfighting reflects the
      evolution of collective compromise formations between the fulfillment of sadistic
      drives and superego sensitivities, as influenced by changing social tolerance.
      The author reviews the most common rationalizations of the spectators, the sexual
      prototypes in bullfighting, the manifestations of envy toward the bullfighter,
      and the public's narcissistic regression due to the grandiose identification with
      him. Some associations from patients are commented upon.

PMID- 7513892
TI  - Nitric oxide synthase inhibition blocks tolerance to the analgesic action of
      kappa-opiate receptor agonist in the rat.
AB  - The effect of NG-monomethyl-L-arginine (NMMA), an inhibitor of nitric oxide
      synthase, on the development of tolerance to the analgesic and hypothermic
      actions of U-50,488H, a highly selective kappa-opiate agonist, was determined in
      the rat. Male Sprague-Dawley rats were rendered tolerant to the pharmacological
      actions of U-50,488H by twice daily intraperitoneal injections of the drug (25
      mg/kg) for 4 days. To determine the effect of NMMA on tolerance to U-50,488H,
      NMMA was administered 10 min prior to each injection of U-50,488H. Multiple
      injections of U-50,488H resulted in the development of tolerance to its analgesic
      and hypothermic actions. NMMA (2, 4 and 8 mg/kg) inhibited the development of
      tolerance to the analgesic but not to the hypothermic action of U-50,488H.
      Multiple injections of U-50,488H resulted in a slower gain in body weight which
      was not modified by treatment with NMMA. The results indicate that inhibition of
      nitric oxide synthase can selectively block the tolerance to its analgesic action
      in the rat.

PMID- 7513894
TI  - [The value of diagnostic imaging in benign prostatic hyperplasia and prostatic
      cancer].
AB  - Diseases of the prostate are of high socioeconomic importance owing to their high
      incidence and prevalence rates. Benign prostatic hyperplasia (BPH) can be
      detected in 80% of males over the age of 80. Clinical symptoms do not correlate
      with organ enlargement. Only 10% of patients with BPH need surgical treatment.
      The decision for surgical treatment is made as a result of objective findings and
      the symptoms reported by the patient. Preoperative evaluation of BPH must include
      digital rectal examination (DRE), measurement of peak flow rate, sonographic
      estimation of residual urine, transrectal ultrasound (TRUS), urethrocystography
      and the assessment of subjective complaints using symptom scores. Prostatic
      carcinoma is the most common malignancy in men. An abnormal DRE, increased PSA
      level and/or hypoechogenic lesions in TRUS are indications for prostate biopsy.
      The sensitivity of TRUS is superior to that of CT and MRI. New MRI techniques are
      promising with regard to local tumour extent. Whereas CT and MRI are not useful
      in screening of patients, these methods are valuable diagnostic tools in the
      follow-up of prostate cancer.

PMID- 7513895
TI  - [Sonographic diagnosis of prostatic cancer].
AB  - In 75-80% of all clinically significant prostate cancer, the peripheral zone
      appears to be hypoechoic on transrectal ultrasound (TRUS). However, examination
      by TRUS alone in a screening program is not recommended due to its low
      sensitivity. The combination of prostate-specific antigen, digital rectal
      examination, and TRUS increases the detection rate of prostate cancer. In
      prostate cancer arising from the transition zone, TRUS findings are often
      nonspecific. Even prostate biopsies might be negative due to the location of this
      tumor. Anterior biopsies of the transition zone will identify these prostate
      cancers. Color Doppler ultrasound of the prostate has little additional value
      over TRUS alone in the diagnosis of prostate cancer.

PMID- 7513896
TI  - [Cold shock response of microorganism].

PMID- 7513897
TI  - Relationship between renal mass and atrial natriuretic peptide release. 1.
      Paradoxical effect of unilateral nephrectomy on serum atrial natriuretic peptide
      in rats.
AB  - Serial serum atrial natriuretic peptide (ANP) determinations were performed in 15
      uninephrectomized Charles River rats and in 15 sham-operated control animals
      during the 60 days following surgery. In a second group of 7 control and 7
      uninephrectomized animals, housed in metabolism cages, serum ANP, body weight, 24
      hour urine volume, osmolality and sodium excretion were serially measured. In a
      third group of uninephrectomized and control rats the effect of acute salt
      loading 24 h, 6 and 60 days after surgery on serum ANP was studied. No
      significant changes in ANP levels were observed during the 60 days following
      surgery in control animals. In the uninephrectomized animals a sharp drop in
      basal ANP levels was evident 24 and 48 h after surgery, but increased levels of
      serum ANP were seen from day 6 to 28. Thereafter ANP returned to baseline levels
      for the rest of the study period. Urinary sodium excretion decreased in the
      nephrectomized animals on days 1 and 2 following surgery. No such change was seen
      in the control animals during the same period. Body weight, 24-hour urine volume
      and urine osmolality were not statistically different in the nephrectomized vs.
      control rats at any time and remained constant in each group throughout the
      experimental period. Central venous pressure (CVP) did not change significantly
      in both groups 24 h and 6 days following surgery. CVP rose similarly in both
      groups immediately following saline loading and returned to preload levels 1 h
      later.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513898
TI  - Relationship between renal mass and atrial natriuretic peptide release. 2. Acute
      effects of various degrees of renal damage on atrial natriuretic peptide release
      in rats.
AB  - We studied basal serum atrial natriuretic peptide (ANP) levels and the response
      to acute salt loading in rats with different grades of functional renal mass
      reduction. The six groups of rats studied included 2 controls, i.e. unoperated (n
      = 12) and sham-operated (n = 24) groups. Each of the 4 experimental groups (n =
      24 in each) underwent one of the following procedures: bilateral nephrectomy;
      unilateral nephrectomy; bilateral ureteral ligation; unilateral ureteral
      ligation. Basal ANP was assessed in the intact controls and operated groups 4, 8,
      16 and 24 h after surgery. In addition, ANP was determined in the sham-operated
      controls and in the experimental groups 1 h following acute intravenous saline
      loading performed 4 h after surgery with central venous pressure monitoring.
      Basal ANP dropped significantly following bilateral nephrectomy but was not
      significantly altered after unilateral nephrectomy or the two modalities of
      ureteral ligation. In all 4 experimental groups ANP failed to rise after saline
      loading. We conclude that substantial renal damage results in early impairment in
      ANP secretion suggesting the existence of a renal physiological stimulus
      controlling ANP release by cardiac atria.

PMID- 7513900
TI  - Influence of cell culture conditions and passage number on the response of
      membrane voltage to ATP and angiotensin II in rat mesangial cells.
AB  - The influence of passage number and different culture conditions on the effect of
      ATP and angiotensin II (A II) on membrane voltage (Vm) of rat mesangial cells
      (MC) was examined with the patch clamp technique in slow and fast whole cell
      recordings. MC were characterized immunologically and grown in standard medium in
      primary culture (PC) and long-term culture up to passage 21 in the presence of 90
      g/l fetal calf serum (LTC/+FCS) or without or with 5 g/l FCS for 1-3 days (LTC/
      FCS). In all three series the studies were performed in a FCS-free Ringer-like
      solution. Vm of MC did not differ in the series (PC: -49 +/- 1 mV, n = 151;
      LTC/+FCS: -52 +/- 1 mV, n = 49; LTC/-FCS: -51 +/- 1 mV, n = 44). In primary
      culture and long-term cultured MC up to passage 8, FCS (ED50 approximately 5
      g/l), ATP (ED50 approximately 2 x 10(-6) mol/l) and A II (ED50 approximately 5 x
      10(-10) mol/l) induced a depolarization of Vm. Reduction of extracellular Cl-
      concentration (from 145 to 32 mmol/l) had no effect on Vm but led to an increased
      depolarization of Vm by FCS, ATP and A II. In long-term cultured MC above passage
      8 grown with 90 g/l FCS both ATP and A II induced a concentration-dependent
      hyperpolarization of Vm, which was attenuated in increased extracellular K+
      concentration (from 3.6 to 33.6 mmol/l). In long-term cultured MC beyond passage
      8, grown without or with a reduced FCS concentration of 5 g/l, ATP and A II led
      to a transient depolarization of Vm, which was increased in the presence of 32
      mmol/l extracellular Cl-. The depolarization was followed by a hyperpolarization,
      which was attenuated in the presence of increased extracellular K+. The data
      indicate that vasoactive agents depolarize Vm of MC in primary culture by
      activating a Cl- conductance, whereas they hyperpolarize Vm by activation of a K+
      conductance in long-term cultured MC grown with FCS. The latter effect was
      partially reversed when FCS was omitted.

PMID- 7513899
TI  - Simple device for continuous measurement of fluorescent anions and cations in the
      rat kidney in situ.
AB  - A simple device for fluorescence measurements on kidney surface in situ (FKS) is
      described. The device consists of (1) an illuminating unit, (2) a detector, (3)
      an evaluation unit. The device was developed for measurement of tissue content of
      anionic sulfofluorescein and cationic 4(4-dimethylaminostyryl)-N-methylpyridinium
      (ASP) during its secretion by proximal renal tubular cells.

PMID- 7513901
TI  - Isolation of single mammalian proximal tubule cells: effects of hypotonic shocks
      on cell yield and function.
AB  - Nord et al. [Am J Physiol 1986; 250:F539-F550] proposed a method to give a high
      yield of proximal tubule cells by exposing a suspension of rabbit cortical
      tubules to a hypotonic shock in calcium-free media. The present study describes
      the effects of both amplitude and duration of the hypotonic treatment on some
      transport-related characteristics of individual cells as compared to the starting
      tubule suspension. The averaged cell yield increased by an order of magnitude
      when the osmolality of the hypotonic solution was varied in four steps from 200
      (C200 cells) to 70 mosm/kg H2O (C70 cells) while the proportion of trypan blue
      positive cells progressively decreased from 33% for C200 cells to 9.5% for C70
      cells. An increase in duration of the hypotonic shock from 0.5 to 6 min did not
      change the cell yield of C200 cells while it significantly increased that of C70
      cells by 61%. Basal and ouabain-sensitive oxygen consumption (QO2) increased by
      57 and 155%, respectively, from C70 to C200 cells but was approximately one order
      of magnitude smaller than the QO2 measured for tubule suspension. Intracellular
      ATP content averaged 5.5 +/- 0.8 nmol/mg for the starting tubule suspension, 4.6
      +/- 0.8 nmol/mg for C70 cells but only 1.3 +/- 0.1 nmol/mg for C200 cells. The
      maximal velocity for phloridzin-sensitive alpha-methyl glucose transport averaged
      13.7 +/- 1.7 nmol min-1 mg-1 for C70 cells and only 6.3 +/- 1.3 nmol min-1 mg-1
      for C200 cells which is approximately one order of magnitude smaller than what
      can be expected from a tubule presenting a good access to luminal membrane. We
      conclude from these results that, in the process of isolating individual cells
      from a polarized epithelium, membrane transport rates have decreased by one order
      of magnitude and this reduction is intensified by a large hypotonic shock. In
      comparison with C200 cells, the cells obtained with a large hypotonic shock give
      a high yield, a larger proportion of trypan blue-negative cells and their lower
      overall transport rate allows the cells to maintain a better electrochemical
      gradient for Na and a higher intracellular ATP level.

PMID- 7513902
TI  - Characterization of the synthesis and release of dopamine in LLC-PK1 cells.
AB  - The ability of a renal epithelial cell line of porcine origin (LLC-PK1) to
      synthesize dopamine (DA) from L-dopa and release DA into the culture media was
      studied. L-Dopa was rapidly taken up by LLC-PK1 cells and converted to DA which
      was then released into the media. L-Dopa uptake and conversion to DA was
      competitively inhibited by other aromatic amino acids (Tyr and Phe). Studies were
      conducted to assess L-dopa uptake, DA synthesis and DA release in LLC-PK1 cells
      in response to changes in the ionic composition of the Krebs-Ringer bicarbonate
      (KRB) buffer media and to various drugs known to alter renal transport function.
      Sodium chloride addition to KRB media resulted in enhanced DNA release into the
      media that was significantly attenuated by both quinine (1 mM) and benzamil (0.1
      mM). Other sodium salts (sodium acetate and sodium phosphate) also enhanced DA
      release from LLC-PK1 cells. Salts containing chloride (LiCl, NH4Cl, choline
      chloride) stimulated a greater efflux of DA from LLC-PK1 cells than sodium salts
      at equimolar concentrations. Osmotic stimuli (sucrose, mannitol and dextran, 50
      200 mM) also elicited increased DA release from LLC-PK1 cells into the media but
      not to the same extent as inorganic salts. DA release (secretion) from LLC-PK1
      cells was strongly inhibited (25-50%) by drugs known to be substrates for the
      renal cation transport system. These studies have characterized extensively the
      factors that govern and regulate the synthesis of DA from L-dopa and the
      transport system responsible for the secretion (release) of intracellular DA into
      the media.

PMID- 7513903
TI  - [Immunoglobulins. Structure, monoclonal or polyclonal characteristics, genetic
      bases and function].

PMID- 7513904
TI  - Role of bone marrow-derived cells in presenting MHC class I-restricted tumor
      antigens.
AB  - Many tumors express tumor-specific antigens capable of being presented to CD8+ T
      cells by major histocompatibility complex (MHC) class I molecules. Antigen
      presentation models predict that the tumor cell itself should present these
      antigens to T cells. However, when conditions for the priming of tumor-specific
      responses were examined in mice, no detectable presentation of MHC class I
      restricted tumor antigens by the tumor itself was found. Rather, tumor antigens
      were exclusively presented by host bone marrow-derived cells. Thus, MHC class I
      restricted antigens are efficiently transferred in vivo to bone marrow-derived
      antigen-presenting cells, which suggests that human leukocyte antigen matching
      may be less critical in the application of tumor vaccines than previously
      thought.

PMID- 7513905
TI  - RNAs with dual specificity and dual RNAs with similar specificity.
AB  - The biological role of RNA is delimited by its possible reactions, which can be
      explored by selection. A comparison of selected RNAs that bind one ligand with
      those that bind two related ligands suggests that a single nucleotide
      substitution can expand binding specificity. An RNA site with dual (joint)
      specificity has adenine and cytosine bases whose pKa's appear shifted upward,
      thereby mimicking an efficient general acid-base catalyst. The joint site also
      contains two conserved, looped arginine-coding triplets implicated in arginine
      site formation. Two selected joint RNAs are identical in some regions and
      distinct in others. The distinct regions, like some peptides, seem to function
      similarly without being similar in primary structure.

PMID- 7513906
TI  - Unresectable hilar cholangiocarcinoma: percutaneous versus operative palliation.
AB  - BACKGROUND: Several nonoperative and operative options are available for
      palliation of patients with unresectable hilar cholangiocarcinoma. This
      retrospective analysis compares the results of nonoperative percutaneous stenting
      and operative palliation in 65 patients. METHODS: Twenty-one patients were
      managed with percutaneous biliary stents (group A), and 44 patients underwent
      laparotomy (group B) with placement of large-bore silicone rubber transhepatic
      stents in 33. The two groups were similar with respect to age, gender, mean
      laboratory data, and cholangiographic extent of tumor. RESULTS: Group A and group
      B patients were comparable in hospital morbidity (67% vs 61%), hospital mortality
      (14% vs 7%), and mean initial hospital stay (27 vs 31 days). Survival was greater
      in group B laparotomy patients at 1, 3, and 6 months (p < 0.01), and median
      survival was 5 months for group A compared with 8 months for group B patients (p
      = 0.06). Group A patients who were managed with percutaneous stents required more
      stent changes per month of survival (0.5 vs 0.3, p = 0.06). However, group B
      patients who underwent operative palliation were more likely to undergo a second
      operation (0% vs 21%, p = 0.05), most often for duodenal or small-bowel
      obstruction. CONCLUSIONS: Operative placement of large-bore transhepatic stents
      may reduce cholangitis, delay hepatic failure, and prolong survival. We conclude
      that patients with unresectable hilar cholangiocarcinoma who are fit for surgery
      may benefit from operative palliation.

PMID- 7513907
TI  - Prooxidant and antioxidant properties of iron-hydroquinone and iron-1,2,4
      benzenetriol complex. Implications for benzene toxicity.
AB  - Bleomycin-dependent degradation of DNA in bone marrow cells was studied in vitro
      in the presence of iron or iron polyphenol chelates which are formed during
      biotransformation of benzene. Iron polyphenol chelates markedly enhanced
      bleomycin-dependent DNA degradation in comparison to iron alone. About 1.5 and
      2.5-fold increase was observed in the presence of iron hydroquinone (HQ) chelate
      and iron 1,2,4-benzenetriol (BT) chelate, respectively. Endogenous iron chelators
      such as glutamate, citrate, aspartate, glycine, cysteine, dithiothreitol, AMP,
      ADP and ATP did not enhance iron-catalysed bleomycin-dependent degradation of
      DNA. By bleomycin assay, the recovery of iron polyphenol chelate added externally
      to bone marrow lysate was complete. However, the presence of iron polyphenol
      chelate resulted in less thiobarbituric acid reactive products from glutamate or
      brain homogenate than with iron alone. The optical spectra of BT were modified in
      the presence of ferrous sulphate, revealing a new absorption peak at 259 nm
      indicating complexation with iron. Thus, the iron polyphenol chelate, on one
      hand, is a more potent DNA cleaving agent in the presence of bleomycin, and on
      the other hand, it is a less effective free radical generator as compared to iron
      alone.

PMID- 7513908
TI  - Changes in ABH antigen expression on red cells during in vivo aging: a flow
      cytometric analysis.
AB  - BACKGROUND: During aging of red cells they undergo a multitude of physical and
      chemical changes. STUDY DESIGN AND METHODS: Age-dependent changes in the
      expression of ABH major blood group antigens on red cells were studied in a two
      variable flow cytometric analysis. The expression of the antigens was measured
      after staining with fluorescence antibodies (for A and B) or lectin (for H). Cell
      age was related to size as measured by forward light scattering. Aging senescent
      cells are smaller and have low forward light scattering properties. RESULTS: The
      results indicated that, within a given population, the A and/or B and H antigens
      decreased with the decrease in forward light scattering (i.e., increase in age),
      but A and B antigen expression decreased to a greater extent than did H.
      CONCLUSION: During aging, red cells lose the antigens of the major blood groups,
      but the degree of this loss is related to the fact that these antigens are
      located on the cell surface.

PMID- 7513909
TI  - Evaluation of monoclonal anti-glycophorin B as an unusual anti-S.
AB  - BACKGROUND: Monoclonal antibody 148 is a murine monoclonal anti-glycophorin B
      that preferentially reacts with S+ human red cells. STUDY DESIGN AND METHODS:
      Serologic and immunochemical studies were performed using red cells with various
      phenotypes. RESULTS: These studies reveal that this monoclonal antibody is
      unusual in that it fails to agglutinate S+ TSEN+ red cells and agglutinates S-
      St(a+) and S- Dantu+ red cells. CONCLUSION: These results allow the prediction of
      the glycophorin composition of GP.Hop (Mi.IV) red cells.

PMID- 7513910
TI  - Hepatitis C viremia in German blood donors: serum alanine aminotransferase is not
      a valid marker for screening.

PMID- 7513911
TI  - FK506 conversion therapy in pediatric liver transplantation.
AB  - The safety and efficacy of conversion to FK506 after failing immunosuppression
      with cyclosporine was prospectively evaluated in 31 pediatric liver transplant
      recipients between April 1991 and March 1993. The patients, who ranged in age
      from 40 days to 14 years, accounted for 28 primary transplantations and 3
      retransplantations. The initial immunosuppression regimen consisted of
      cyclosporine in combination with prednisone. The indications for conversion were
      acute or chronic rejection refractory to OKT3, Minnesota antilymphocyte globulin,
      or steroids (13 patients); hypertension (8 patients); inability to reach a
      therapeutic level of cyclosporine (6 patients); hirsutism (3 patients); and
      growth retardation (1 patient). After an average follow-up of 10 months (range, 2
      to 25 months), 27 (87%) of the patients are alive and have functioning grafts. Of
      the 13 patients who were converted for refractory rejection, 9 are alive. Six of
      these 9 patients experienced a complete biochemical reversal of the rejection
      process within 3 months of conversion; 2 had a partial response to conversion,
      and 1 patient failed but underwent successful retransplantation. Three of the 4
      patients who died did so without showing any improvement. The remaining 18
      patients who were converted for various other reasons are alive and have
      functioning grafts. Of the 8 patients who developed hypertension on cyclosporine
      and prednisone, 6 experienced a resolution of this problem within 3 months of
      conversion. Three of the 18 children who underwent rescue therapy for reasons
      other than refractory rejection experienced rejection episodes after conversion
      to FK506. Two of these 3 children achieved resolution with either steroid therapy
      or an increased dosage of FK506, while the third child developed chronic
      rejection. The side effects of FK506 were generally minor and resolved by
      lowering the dose. Lymphoproliferative disease developed in 2 patients (6%). The
      present study suggests that FK506 is a relatively safe and effective rescue
      therapy for pediatric liver transplant recipients who have failed
      immunosuppression with cyclosporine. Longer follow-up is needed to assess the
      effect of FK506 on growth.

PMID- 7513912
TI  - The deleterious effects of long-term cyclosporine A, cyclosporine G, and FK506 on
      bone mineral metabolism in vivo.
AB  - Administration of cyclosporine A to male and female rats accelerates bone
      remodeling and causes bone loss, among other side-effects. The newer
      immunosuppressant drugs, FK506 and CsG, have been synthesized to counteract the
      toxic effects of CsA, yet maintain clinical efficacy. We investigated the in vivo
      effects of long-term administration of these drugs on bone mineral metabolism in
      the rat. Five groups of Sprague-Dawley rats, 15 per group, were allocated to
      receive by daily gavage for a period of 28 days: (1) Cs-vehicle; (2) CsA 15 mg/kg
      b.w.; (3) CsG 15 mg/kg b.w.; (4) FK506 vehicle; (5) FK506 5 mg/kg b.w. Blood was
      sampled on days 0, 14, and 28 for measurement of ionized calcium (Ca2+),
      parathyroid hormone (PTH), 1,25-(OH)2-vitamin D, and bone gla protein (BGP).
      Tibiae were removed on day 28 after double calcein labeling for histomorphometric
      analysis. Immunosuppressant groups were compared with the respective vehicle
      groups. Neither CsA or CsG affected the levels of Ca2+ or PTH, whereas by day 28
      FK506 caused a decrease in Ca2+ and a corresponding rise in PTH (P < 0.05). The
      1,25-(OH)2-vitamin D and BGP levels in both the CsA and CsG groups were increased
      on days 14 and 28 (P < 0.05), while FK506 had no effect on these serum levels.
      Tibial bone histomorphometry revealed that all 3 immunosuppressants increased
      measures of bone formation and bone resorption, accompanied by a significant
      reduction in percent trabecular area, most marked with FK506. This report
      demonstrates that all three immunosuppressants have adverse effects on bone--most
      deleterious with FK506.

PMID- 7513914
TI  - Triphenyltetrazolium chloride reduction assay for determination of the viability
      of the cold-preserved rat liver.

PMID- 7513913
TI  - A comparison of corneal, pancreas, and skin grafts in mice. A study of the
      determinants of tissue immunogenicity.
AB  - A model of murine heterotopic allogeneic transplantation was used to study the
      rejection characteristics of three tissues--adult cornea, fetal pancreas, and
      fetal skin--for attributes that might explain their variation in rejection rates
      and help define the determinants of graft immunogenicity. Under identical
      conditions, tissues were transplanted to the renal subcapsular space and their
      base-line rejection rates compared. The expression of MHC class I and II and
      intercellular adhesion molecule-1 (ICAM-1), was determined for each tissue, as
      was their ability to produce interleukin-6, IL-3, interferon-gamma, and
      granulocyte-macrophage colony-stimulating factor in vitro. These studies were
      performed under basal conditions and after stimulation with concanavalin A
      stimulated spleen cell supernatant (CAS) or INF gamma. Corneal grafts had a slow
      rejection rate compared with pancreas and skin. While all three tissues had low
      basal expression of MHC class II, both fetal skin and pancreas, but not adult
      cornea, were able to increase this under our experimental conditions. Pancreas
      and skin produced IL-6 under basal conditions and could be stimulated to increase
      production 2-3-fold but the cornea did not basally produce IL-6 and showed
      minimal upregulation. We postulate that delayed corneal rejection, compared with
      pancreas and skin, results from two compounding deficiencies: the relative lack
      of class II MHC-positive APC and the inability to overcome this deficiency by
      upregulating class II expression and producing accessory molecules for antigen
      presentation.

PMID- 7513915
TI  - Bladder carcinoma producing granulocyte colony-stimulating factor.
AB  - A patient presented with grade 3 transitional cell carcinoma of the bladder
      showing a marked increase in granulocyte colony-stimulating factor (G-CSF). G-CSF
      was identified in the carcinoma by immunohistochemical procedures. The serum and
      urinary levels of G-CSF were persistently elevated during his clinical course.
      These results suggest that the carcinoma produced G-CSF and was responsible for
      its high levels in serum and urine.

PMID- 7513916
TI  - [Effect of the natural history on management of adenocarcinoma of the prostate].
AB  - The natural history of prostate cancer has long been regarded as unpredictable.
      The discrepancy between histologically identifiable (40%) and clinically
      diagnosed carcinomas (8%) led to the term of "latent" prostate cancer and to
      considerable diagnostic and therapeutic dilemmas. Based on our previous studies
      showing that biological aggressivity of prostate cancer is a direct function of
      tumor volume and that tumor volume and serum PSA are proportional, we evaluated
      two basically different groups of patients. The first group consisted of 43
      patients with untreated carcinomas of the prostate followed with serial PSA
      determinations. The exponential (log-linear) rise in PSA led us to the conclusion
      of an exponential tumor growth rate. The median doubling time of clinically organ
      confined tumors was 4 years and became shorter with higher clinical stages and
      poorly differentiated histological grades. The second group consisted of 139
      patients who underwent cystoprostatectomy for bladder cancer and had no evidence
      for simultaneously identifiable prostate cancer. In 55 patients (40%),
      unsuspected prostate cancer was found in the specimen; the volume distribution of
      these carcinomas was exponential. These 139 men included 11 (7.9%) who had a
      prostate cancer with a volume greater than 0.5 cm3, corresponding to the 8% risk
      for a man being diagnosed within his lifetime with a clinically significant
      carcinoma of the prostate. We conclude that the other 44 carcinomas, which were
      less than 0.5 cm3 in volume, will never reach clinical significance because of
      their small size and their long doubling time; in this sense they can be
      considered latent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513917
TI  - Identification of serotype-specific and nonserotype-specific B-cell epitopes of
      coxsackie B virus using synthetic peptides.
AB  - Coxsackie B viruses are thought to be involved in the induction of myocarditis.
      However, the diagnosis of acute infections by serology even today is practically
      impossible. The major problem is that no antigenic determinants of coxsackie B
      viruses have been identified or characterized which could be used as antigens in
      a rapid routine antibody screening test. Therefore, we synthesized overlapping
      peptides according to the sequence of the capsid protein VP1 of coxsackie B3
      (CB3) virus in order to identify antigenic determinants located on VP1. Using
      sera raised against CB3 in mice, we were able to identify several antigenic
      determinants of CB3. Here we present a characterization of three epitopes found.
      We also tested the type-specificity of these antigenic determinants by using
      rabbit antisera against coxsackie viruses B1-B6. One antigenic determinant,
      peptide VP1-1, representing residues 1-15 of VP1, reacted highly type-specific
      for CB3. A second antigenic determinant (peptide VP1-3, residues 21-35 of VP1)
      reacted as well with the anti-CB3 sera as with the anti-CB4 sera. Therefore, the
      peptide VP1-3 seems to represent a non-type-specific antigenic determinant of
      coxsackie B viruses. Peptide VP1-24 (residues 229-243 of VP1) showed broad cross
      reaction with anti-CB sera except with the anti-CB1 sera. This identification of
      type-specific and non-type-specific epitopes of coxsackie B viruses may provide
      the basis for the establishment of an effective and fast antibody screening test
      for coxsackie B viruses in patients with clinically suspected myocarditis.

PMID- 7513919
TI  - Chimeric hepatitis B core antigen particles containing B- and Th-epitopes of
      human papillomavirus type 16 E7 protein induce specific antibody and T-helper
      responses in immunised mice.
AB  - The use of hepatitis B core antigen (HBcAg) as an immunogenic delivery vehicle
      for foreign epitopes has been reported. Here we report the insertion of DNA
      sequences encoding immunodominant linear B-epitopes and a "universal" T-helper
      epitope of human papillomavirus (HPV) type 16 E7 transforming protein into the
      full-length HBcAg gene cloned into an inducible bacterial expression plasmid
      (pPN1.0). The resulting chimeric proteins assembled into particles which were
      highly immunogenic. Mice immunised with particles containing one or two of the
      three E7 B-epitopes under consideration produced strong epitope-specific antibody
      responses with both IgG and IgG2a components which recognised eukaryotic E7. T
      proliferative responses were elicited to the E7 T-epitope as well as HBcAg T
      epitope(s). Lymph node cells from immunised mice produced IL-2 and IL-4 when
      specifically recalled in vitro, indicating stimulation of both Th1 and Th2 helper
      cell compartments. Since HBcAg particles can be administered in adjuvant
      acceptable for human application and can elicit mucosal responses after nasal or
      oral immunisation, these results have implications for vaccine design in HPV 16
      associated anogenital cancer.

PMID- 7513918
TI  - Characterization of the feline host range and a specific epitope of feline
      panleukopenia virus.
AB  - The feline parvovirus subgroup is comprised of viruses isolated from various
      carnivores, including the dog, cat, mink, raccoon, Arctic fox, and raccoon dog.
      Those viruses are > 98% identical in their DNA sequences and are very similar
      antigenically. We have shown that although canine parvovirus (CPV) replicates in
      numerous feline cell lines in vitro it does not infect cats after parenteral
      inoculation (U. Truyen and C. R. Parrish, (1992) J. Virol. 66, 5399-5408). Here
      we use recombination mapping to locate some viral determinants required for
      feline host range, and show that the ability to replicate in cats was determined
      by the right-hand 45% of the genome, most likely a function of the capsid protein
      gene. Efficient replication in the cat appeared to require feline panleukopenia
      virus sequences from both ends of the VP2 molecule, which contained differences
      of VP2 amino acid residues 80, 564, and 568. The difference at amino acid 80 was
      also associated with expression of an FPV-specific antigenic epitope. The
      differences which affected the feline host range were located in a region of the
      capsid structure where three VP2 molecules interact, and the mutations gave rise
      to changes in the conformation of loops of the three adjoining VP2 monomers. The
      mechanism(s) of the in vivo feline host range restriction were not defined, and
      we were unable to show in vitro inhibition of virus infectivity by feline serum
      components or erythrocytes.

PMID- 7513920
TI  - Identification and characterization of a murine cytomegalovirus gene with
      homology to the UL25 open reading frame of human cytomegalovirus.
AB  - Monoclonal antibody 1B4, previously shown to be protective in vivo and to cross
      react with both virally encoded and normal host cell proteins, was used to screen
      a lambda gt11 cDNA derived from mRNA harvested from mouse embryo fibroblasts 24
      hr after infection with murine cytomegalovirus (MCMV). A 700-bp cDNA was
      identified representing the 5'terminus of a 2460-bp open reading frame (ORF) with
      significant homology to the human cytomegalovirus UL25 ORF. The UL25 ORF of MCMV
      potentially encodes an 820 amino acid viral tegument protein with an estimated
      molecular weight of approximately 90 kDa. Amino acid homology with eukaryotic
      nucleolins was identified in the acidic N-terminal third of the MCMV UL25
      proteins, suggesting that the protein may be involved in transcriptional
      activation or interactions with chromatin. Northern analysis and S1 nuclease data
      indicated that the gene is expressed late in infection as an approximately 3-kb
      transcript and that expression is dependent on viral DNA replication. An epitope
      recognized by MAb 1B4 was identified using recombinant pGEX plasmids expressing
      fusion proteins representing the N-terminal region of the MCMV UL25 protein. The
      identification of the MCMV UL25 ORF as a member of the CMV-specific UL25/UL35
      gene family provides an opportunity for the investigation of the role these genes
      and their products in CMV pathogenesis in an animal model.

PMID- 7513921
TI  - Mutational analysis of residue 190 of human immunodeficiency virus type 1 reverse
      transcriptase.
AB  - S-2720 and other members of the quinoline/quinoxaline class of HIV-1-specific
      nonnucleoside reverse transcriptase inhibitors (NNRTIs) select for a glycine to
      glutamate substitution at residue 190 (Gly 190 Glu) of the reverse transcriptase
      (RT), when drug-resistant viruses are generated in cell culture. This mutation
      has not been described to appear upon selection for resistant viral variants
      using derivatives of any other class of NNRTIs. Notably, the RNA-dependent DNA
      polymerase activity of the Gly 190 Glu mutant enzyme is drastically diminished
      with respect to the wild-type RT. We describe here the effects of other amino
      acid substitutions at position 190 of the RT that were introduced by using site
      directed mutagenesis. Polymerase activities and sensitivities to inhibition by a
      number of NNRTIs were determined for the different RT mutants. In general, an
      inverse correlation was found between the enzymatic activity and increasing
      length of the side chain, whereas the size of the residue and the level of
      resistance to NNRTIs appeared to be positively related. Double mutants, which
      contain the Gly 190 Glu mutation together with substitutions that confer
      resistance to other RT inhibitors, were all shown to possess severely diminished
      polymerase activity.

PMID- 7513922
TI  - Epitope detection in the envelope of intracellular naked orthopox viruses and
      identification of encoding genes.
AB  - Monoclonal antibodies (MAbs) were generated against vaccinia virus, cowpox virus
      KR2 Brighton, monkeypox virus Copenhagen, or ectromelia virus. Pairwise epitope
      specificity studies by competition ELISAs identified 23 distinct antigenic sites
      in 19 different orthopox virus strains. Six epitopes were completely independent
      of each other, and 17 closely related antigenic sites formed three separate
      epitope complexes. As shown by immunogold electron microscopy (ELMI), all MAbs
      reacted with epitopes in the envelope of intracellular naked virus, 16 MAbs
      recognized proteins of 32, 30, 16 or 14 kDa in Western blotting (WB), and 9 MAbs
      neutralized virus infectivity. In rabbitpox virus (RPV) 18 epitopes were
      detected. A lambda gt11 expression library of RPV DNA was screened with the
      corresponding 18 MAbs. Fourteen recombinant bacteriophage clones (ph) were
      isolated. Cross-hybridizations of phage and RPV DNA demonstrated a reaction with
      the HindIII A, HindIII D, or HindIII H fragments, respectively. DNA of ph3D was
      related to the A25L gene, which corresponds to the A-type inclusion body gene of
      cowpox virus. Two phage clones contained sequences of the 14-kDa fusion protein
      gene (A27L gene). Ph1A contained nearly the entire 14-kDa gene encoding 4
      neutralizing (neutr) and 2 nonneutr epitopes. Ph5, expressing only half of this
      gene product, encoded 1 nonneutr epitope. The fusion protein of vaccinia virus
      MVA was isolated by immune-affinity chromatography with a neutr. catching MAb.
      The protein formed hollow rods (ELMI) and the 6 antigenic sites that were present
      were identical to those expressed by Escherichia coli infected with ph1A. WB
      detection with a polyclonal hyperimmune serum detected protein bands of 54, 32,
      30, 16, and 14 kDa. The catching MAb bound only to a 16-kDa band. The purified
      fusion protein induced neutralizing antibodies in mice and rabbits.

PMID- 7513924
TI  - Structural features unique to a new 405-nucleotide satellite RNA of cucumber
      mosaic virus inducing tomato necrosis.
AB  - The complete nucleotide sequence of a new satellite RNA (KN-satRNA) of cucumber
      mosaic virus (CMV) strain KN, isolated from tomato plants showing severe
      necrosis, has been determined by the analysis of a full-length cDNA clone from
      which biologically active transcript was produced. KN-satRNA was 405 nucleotides
      and is the largest among the known CMV-satRNAs. Comparison of the sequence with D
      CARNA5 (335 nucleotides) revealed three extensive homologous regions, which were
      the 5' region (position 1-80), the 3' half (position 213-405), and a middle
      section (position 116-177) of the molecule. The total length of the three regions
      covers almost the entire molecule of D-CARNA5. Thus, it is apparent that
      insertions would occur at two sites of D-CARNA5, positions 81-86 and 146, to
      evolve the larger size satRNA. These insertions did not alter the proposed
      secondary structure model of Q-satRNA. The in vitro transcript of the cDNA clone
      of KN-satRNA induced necrosis on tomato which was identical to that of native KN
      satRNA. The 3'half of the RNA contained the "necrogenic consensus" sequence
      reported for other satRNAs, to which the pathogenicity of KN-satRNA may be
      attributed.

PMID- 7513923
TI  - Identification of binding sites for neutralizing monoclonal antibodies on the 14
      kDa fusion protein of orthopox viruses.
AB  - A 14-kDa gene-specific probe of vaccinia virus Western Reserve (WR) hybridized to
      homologous sequences in the genomes of the orthopox virus species cowpox,
      camelpox, mousepox, and monkeypox virus. The corresponding genes were mapped and
      sequenced. Homologies of more than 95% were found when compared to the 14-kDa
      gene of vaccinia virus WR. However, point mutations which led to alterations in
      the amino acid sequences were mainly located between residues 26 and 40. By use
      of synthetic peptides, this part of the 14-kDa fusion protein could be identified
      as the binding site for four different neutralizing monoclonal antibodies.

PMID- 7513925
TI  - Changes in the amino acid sequence of the coat protein readthrough domain of
      potato leafroll luteovirus affect the formation of an epitope and aphid
      transmission.
AB  - Potato leafroll luteovirus (PLRV) is transmitted naturally by aphids, but two
      isolates (15 and V) are known to be only poorly transmissible (PAT); these
      isolates are also distinct in that their particles lack an epitope present in
      transmissible (HAT) isolates of PLRV (Tamada et al., Ann. Appl. Biol. 104, 107
      116, 1984; Massalski and Harrison, J. Gen. Virol. 68, 1813-1821, 1987). Virus
      cultures propagated vegetatively for several years in potato plants from the
      source of isolate V were shown still to be poorly transmissible by Myzus
      persicae. Moreover, when isolate V was transmitted by aphids, the subisolates
      obtained (V4 and V31) were no more readily transmissible than was the stock
      culture PLRV-V. The subisolates were also unchanged antigenically by the
      transmission. Thus the inefficient transmission had not restored the properties
      of HAT isolates. Sequence comparisons among the coat proteins and the readthrough
      domains of HAT and PAT Scottish isolates suggested that either or both of two
      amino acid changes in the C-terminal part of the readthrough protein are
      responsible for the poor transmission and the loss of an epitope. The readthrough
      protein is therefore thought to play a role in the circulative aphid transmission
      of PLRV.

PMID- 7513927
TI  - Identification of overlapping class I and class II H-2d-restricted T cell
      determinants of influenza virus N1 neuraminidase that require infectious virus
      for presentation.
AB  - The requirement for endogenous viral protein synthesis in helper and cytotoxic T
      cell (CTL) recognition of influenza virus was studied at the level of individual
      epitopes. The viral envelope glycoprotein neuraminidase (NA) contains class I and
      class II major histocompatibility complex (MHC)-restricted T cell determinants
      that are presented by virus-infected antigen-presenting cells (APC). We had
      previously shown that recognition of NA by class II I-Ed-restricted T cells
      required either active viral infection of APC or introduction of uv-inactivated
      virus to the cytosol, similar to the well-established requirements for class I
      restricted responses. Detailed mapping of T cell epitopes was undertaken using
      vaccinia virus vectors encoding truncated segments of the influenza NA molecule
      and by synthetic peptides. Class I MHC-restricted CTL were found to recognize two
      regions of NA: residues 69-89 in the context of Dd and 191-201 presented by Kd.
      Analyses of T cell proliferation and T hybridoma clones revealed that class II
      restricted responses recognized the same two regions as the CTL, presented by I
      Ed and I-Ad, respectively. Interestingly, both class I and class II MHC
      restricted T cells showed similar requirements for endogenously synthesized
      antigen, responding poorly or not at all to endocytosed uv-inactivated virus.
      This extends previous observations that specific epitopes can be preferentially
      presented by class II molecules from endogenously synthesized antigens and shows
      that the same antigenic determinants can have access to both class I and class II
      antigen presentation pathways.

PMID- 7513928
TI  - Detailed diagnoses and procedures, National Hospital Discharge Survey, 1991.

PMID- 7513926
TI  - Agrobacterium-mediated inoculation of PSTVd cDNAs onto tomato reveals the
      biological effect of apparently lethal mutations.
AB  - Potato spindle tuber viroid (PSTVd) mutants which contain alterations in the
      terminal loops of the rod-like native structure have previously been reported
      from our laboratory. PSTVd-P contains mutations at positions 2, 4, and 6 in the
      left terminal loop; PSTVd-R+, a sequence permutation of PSTVd-R, contains the
      same mutations at positions 177 and 178 in the right terminal loop as PSTVd-R and
      contains in addition a 1-nucleotide G insertion at position 176. PSTVd-P, PSTVd
      R, and PSTV-R+ were noninfectious when either cDNA or SP6-generated RNA
      transcripts were used as inoculum onto tomato cotyledons. In the current study,
      mutant and wild-type PSTVd constructs were mobilized into Agrobacterium
      tumefaciens and used for stem inoculation of tomato plants. Agrobacterium
      mediated inoculation of the mutant and wild-type constructs has confirmed the
      inability of the PSTVd-P mutant to establish an infection. The PSTV-R+ mutant
      and/or sequence variants derived in vivo can establish an infection, although
      PSTVd-R+ progeny and replicative intermediates appear to be primarily restricted
      to the gall and root tissues of the plant and only occasionally are progeny
      detectable in the newly developing leaves. The reduced level of viroid
      accumulation from the PSTVd-R+ mutant appears to be consistent with the mutant
      viroid replicating/accumulating only in a limited number of cells or cell types.
      The mutations in the right terminal loop may alter interactions with specific
      host components and thereby disrupt the normal pattern of intercellular transport
      of the viroid or limit its replication to a cell type but not abolish replication
      per se.

PMID- 7513931
TI  - Respiratory syncytial virus nucleocapsid protein (N) expressed in insect cells
      forms nucleocapsid-like structures.
AB  - The gene coding for the N protein of RSV strain Long has been cloned and
      sequenced. It was introduced behind the polyhedrin promoter of the shuttle vector
      pVL941 and baculoviruses containing the N gene were constructed by homologous
      recombination. Infection of Spodoptera frugiperda 9 cells resulted in the
      production of large amounts of a protein similar in size and antigenicity to the
      authentic N protein. The baculovirus expressed N protein was concentrated in the
      cytoplasm of the insect cells and could be extracted at low salt concentration.
      Nucleocapsid structures similar to those purified from RSV-infected cells could
      be observed by electron microscopy after negative staining of cellular extracts.

PMID- 7513930
TI  - [Brain abscess in patients with cyanotic heart defects].
AB  - As a result of hypoxia following right-to-left shunts, cerebral bacterial
      spreading and an altered blood-brain-barrier permeability, brain abscesses (BA)
      are typical complications in patients with cyanotic congenital heart disease. In
      483 prospectively followed patients the incidence of BA was 0.45%/year. It was
      higher (0.57%/year) for patients with tetralogy of Fallot where the cumulative
      risk within the first two decades of life was 12.1 +/- 1.7%. The risk of BA
      complicating cyanotic heart disease is inconstant and continuously increasing up
      to approximately age 12 (instantaneous risk at that time: 1.75 +/- 0.12%),
      decreasing thereafter. With respect to etiology, infectious endocarditis,
      infections per continuitatem, bacterial meningitis, bacterial lung diseases with
      intrapulmonary shunts, and thromboembolic complications of systemic infections
      have to be differentiated. The stepwise diagnosis includes CCT to demonstrate the
      typical contrast enhancement and a lumbar puncture which shows granulocytic
      pleocytosis. If the cerebral spinal fluid fails to demonstrate the typical
      findings, cerebral angiography may be necessary to exclude a malignant
      vascularized neoplasma. In cases of doubt, stereotactic cerebral biopsy should be
      performed. Optimal antibiotic therapy after determining the minimal bactericidal
      concentration and combination of antibiotics is of utmost prognostic
      significance. Cranial computed tomography should be repeated after 6, 14, and 24
      days. Infections resistant to antibiotics may necessitate local instillation of
      antibiotics.

PMID- 7513932
TI  - Tick-borne flavivirus NS1 gene: identification of conserved peptides and
      antigenic analysis of recombinant louping ill virus NS1 protein.
AB  - The nucleotide sequence of the NS1 gene of louping ill (LI) virus has been
      determined. The sequence shows a high degree of homology with other members of
      the tick-borne serocomplex of flaviviruses and a lower homology with the mosquito
      borne flaviviruses. Alignment of the deduced NS1 amino acid sequences with all
      tick-borne flavivirus NS1 sequences, identified four peptide regions which were
      conserved for all tick-borne flaviviruses, but were variable amongst mosquito
      borne flaviviruses. A dendrogram, derived from the alignment of the NS1 protein
      sequences, indicated an evolutionary relationship that quite closely reflects the
      recognised serological classification. The LI virus NS1 protein expressed in
      Escherichia coli and baculoviruses showed similar antigenic reactivity to the
      authentic virus-coded protein when tested with NS1-specific monoclonal
      antibodies, but did not form high molecular weight complexes and was not secreted
      from cells.

PMID- 7513933
TI  - [Polytrauma and multi-organ failure syndrome. Definition--pathophysiology-
      therapy].
AB  - The multiple organ dysfunction syndrome (MODS) with a mortality of 50% to 70%
      represents the number 1 cause of death in surgical intensive care units. It is
      divided in a primary and a secondary MODS based on time of manifestation and
      pathophysiological events which attribute to it. The therapy of the primary MODS
      includes sufficient and quick resuscitation, adequate oxygen delivery and early
      enteral nutrition to reduce or avoid the incidence of bacterial translocation. In
      addition, a reduction of the antigenic load by control of hemorrhage, radical
      wound debridement, decompression, and fixation of long bone fractures appears to
      be effective in reducing the occurrence of MODS. The treatment of the secondary
      MODS remains supportive and its prevention is essential. Further studies have to
      be carried out to evaluate the clinical significance of new therapeutical agents
      such as monoclonal antibodies or cytokine receptor antagonists.

PMID- 7513929
TI  - [After care of locally advanced and metastatic prostate cancer].

PMID- 7513934
TI  - Fluorouracil modulation in head and neck cancer.

PMID- 7513937
TI  - [Influence of anti-androgen therapy for prostatic hypertrophy on lipid
      metabolism].
AB  - Antiandrogen therapy has an important role in the treatment of patients with
      benign prostatic hypertrophy who lack indication for surgery. Herein, the effects
      on lipid metabolism of administration of antiandrogen agents for benign prostatic
      hypertrophy are reported. Eighty patients with benign prostatic hypertrophy were
      each treated with the antiandrogen agents, chlormadinone acetate, allylestrenol,
      gestonolone caproate and oxendolone for 12 months. The levels of total
      cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density
      lipoprotein (LDL), alpha-lipoprotein, apoprotein, and maronediardehyde (MDA) were
      measured every 4 weeks after initiation of antiandrogen treatment. In the
      chlormadinone acetate group, the TG level was significantly decreased between 3
      and 6 months after treatment (p < 0.05). In the oxendolone group, the alpha
      lipoprotein level was also elevated between 3 and 6 months and between 6 to 12
      months after treatment (p < 0.05). The MDA level was also significantly elevated
      6 and 12 months after treatment. However, the levels of the other lipids were
      within the normal range. In conclusion, the changes in the levels of plasma
      lipoprotein, apoprotein and MDA resulting from antiandrogen therapy were unlikely
      to be a cause of ischemic coronary disease.

PMID- 7513938
TI  - Educational media technology for hearing-impaired persons. A federal perspective.

PMID- 7513936
TI  - [Influential clinical and pathological factors on prognosis of renal cell
      carcinoma].
AB  - The clinical, pathological and survival data were analyzed for 42 patients with
      nephrectomy for renal cell carcinoma, who visited our department between 1987 and
      1992. The factors influencing prognosis were evaluated. There were 33 males and 9
      females with an average age of 59.1 years old. Forty-five percent (19 patients)
      of the cases were detected incidentally. These incidental cases showed a higher
      survival rate than the cases with symptoms although the difference was not
      statistically significant. Positive acute phase reactant, clinical stage, grade
      and type of infiltration were to be considerably predictive factors indicating
      poor prognosis. Embolization of renal artery for neo -adjuvant therapy could not
      improve the survival rate. Interferon-alpha for adjuvant therapy did not prolong
      the survival team clearly.

PMID- 7513935
TI  - The role of the reduced-folate carrier and metabolism to intracellular
      polyglutamates for the activity of ICI D1694.
AB  - The uptake of ICI D1694 into L1210 cells is very rapid and evidence strongly
      suggests that transport is via the reduced-folate/MTX cell membrane carrier
      (RFC); for example a cell line with a greatly impaired RFC is highly resistant to
      ICI D1694. Polyglutamates can be found intracellularly within a few minutes, so
      that experiments initially designed to measure transport were actually measuring
      transport and polyglutamation. After 30mins, in normal serum-containing tissue
      culture medium, the concentration of polyglutamates (di, tri and tetra) exceeded
      that of the parent drug 6-fold. Studies where cells were resuspended in drug-free
      medium demonstrated that the parent drug and its diglutamate could readily leave
      the cell. Folinic acid could markedly decrease the polyglutamation of ICI D1694,
      but had to be given simultaneously with the drug as a 4hr delayed rescue was less
      effective because substantial polyglutamation had already occurred. This effect
      was translated into considerable antagonism for cell growth inhibition by
      simultaneous folinic acid. The importance of the metabolism of ICI D1694 to
      polyglutamates to its potent cytotoxic activity is demonstrated by compounds
      related in structure to ICI D1694 but with different properties for the RFC and
      FPGS. For example, 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolate (ICI
      198583) owes its less potent cytotoxic activity to its poorer FPGS substrate
      activity (Km 40 microM compared with 1.3 microM for ICI D1694). Replacing the 2
      methyl of either compound with amino, which appears to prevent use of the RFC,
      has a deleterious effect on growth inhibitory activity presumably by limiting the
      transport of the parent compounds into the cells, thereby slowing the rate of
      polyglutamate formation. Again a single change to another part of the molecule,
      that is methylation of the 7-position can have serious consequences on cytotoxic
      potency, particularly for the ICI D1694 molecule. The 7-methylated compounds are
      apparently poor or non-substrates for FPGS and therefore retain activity against
      a cell line unable to polyglutamate antifolates. These same compounds are only
      slightly affected by coincubation with folinic acid in L1210 tissue culture,
      consistent with the failure of these compounds to form intracellular
      polyglutamates. The results of short-exposure assays and in situ TS assays
      confirms that 7-methylation largely prevents the formation of a retained drug
      form (polyglutamates), continuous exposure being necessary to maintain TS
      inhibition and cause a cytotoxic effect after removal of extracellular
      drug.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7513939
TI  - A technological metamorphosis in the education of deaf students.

PMID- 7513941
TI  - Technology and the transformation of schooling.

PMID- 7513940
TI  - Educational Applications of Technology for Deaf Students. Proceedings of a
      national symposium. Rochester, New York, May 28-30, 1992.

PMID- 7513942
TI  - Using media for developing mental models and anchoring instruction.
AB  - My goal here was to discuss ways in which research and theory in the areas of
      learning and cognition can guide the development of integrated media systems. We
      began our discussion by exploring how IM technology can be used to embellish
      existing curricula, noting that its many advantages are quite obvious.
      Nevertheless, other issues related to IM development are more subtle, yet
      important. We discussed ways that the research literature can help us think about
      these issues in more detail. My major argument was that the full implications of
      exploring existing theory and research cannot be appreciated by simply using IM
      technologies to embellish existing curricula. Based on the cognitive literature,
      there is a need to develop principles for breaking the mold. I provided some
      reasons for doing this and discussed examples of work going on in our center that
      suggest possible alternatives to typical text-based curricula. The major
      characteristic of these alternatives is that they drastically reduce the amount
      of time that students spend receiving already-discovered information (from
      teachers or texts) and, instead, provide problem-rich environments that can be
      explored and discussed by students. Many other examples of alternative problem
      rich environments are currently being developed and studied by others (Bank
      Street College, 1984; Lipman, 1985; Tinker, 1991). As new principles for breaking
      the mold begin to emerge from research, we hope that the result will be major
      advances in learning for all students.

PMID- 7513943
TI  - Two-color multiparametric method for flow cytometric DNA analysis.
      Standardization of spectral compensation.
AB  - Spectral overlap of green fluorescence signals into the red detector (red-minus
      green compensation) is one potential source of variation in two-color flow
      cytometric DNA analysis. Suboptimal compensation in a two-color propidium iodide
      (PI)/fluorescein isothiocyanate (FITC) system may be observed if compensation is
      adjusted using an inappropriate standard, or if changes to fluorescence detector
      high-voltage settings are made without corresponding readjustment of fluorescence
      compensation. To quantitate the influence of red-minus-green compensation on the
      quality of DNA histograms, data from 60 dual PI/cytokeratin (CK)-FITC stained
      carcinomas were acquired in parallel using two compensation standards: a PI/CK
      FITC-stained T24 cell line calibrator overstained to achieve a high-intensity
      green fluorescence standard (HIGFS) with manually set compensation and automated
      compensation settings derived from commercial phycoerythrin/low intensity FITC
      beads (LIGF). Both compensation standards gave similar DNA hyperdiploidy results
      (DNA index, 1.1-2.8). However, LIGF standard yielded two falsely hypodiploid
      peaks (DNA index, .7 and .9). Eight left-skewed peaks became DNA diploid and
      symmetric, respectively, with the HIGFS. Use of HIGFS lowered the coefficient of
      variation percentage in 95% of cases, the greatest differences (maximum, 3.4%;
      mean, 1.81%) in tumors of highest intensity CK-FITC. The authors concluded that
      use of cell-based compensation standards (HIGFS) with intense green signals that
      mimic clinical tumor samples will avoid spurious aneuploidy and maximize
      resolution of near-diploid abnormalities.

PMID- 7513944
TI  - Rapid (one-shot) staining method for two-color multiparametric DNA flow
      cytometric analysis of carcinomas using staining for cytokeratin and leukocyte
      common antigen.
AB  - The authors present an improved method for rapid two-color staining with direct
      conjugated antibodies to cytokeratin and CD45 antigen (leukocyte common antigen)
      for whole-cell, ethanol-fixed preparations of human carcinomas. This method was
      quality controlled with the T24 human bladder tumor cell line and compared in
      parallel analysis of 24 fresh human carcinomas with the original two-color method
      of multiparametric analysis that had been published in 1989. This rapid method
      was designed to achieve comparable staining intensities of both green (phenotype
      directed monoclonal antibody label) and red (propidium iodide labeled DNA)
      fluorescence, identical DNA indexes, comparable coefficients of variation, and
      subjective visual quality of DNA histograms. This is accomplished in a single
      (one-shot), abbreviated incubation with monoclonal antibody diluted in propidium
      iodide-RNase, thereby eliminating two incubations and three wash steps required
      with the original method. The single rinse is done in the propidium iodide-RNase
      staining solution with resuspension in fresh staining solution before analysis.
      With the rapid method, the preparation time is reduced by 130 minutes, resulting
      in a 60% time savings in batch staining mode compared with the original method.
      The time reduction and fewer wash steps, which should avoid excessive cell loss
      and cytoplasmic stripping, may advance the adoption of this two-color method in
      clinical practice.

PMID- 7513945
TI  - Lineage determination of CD7+ CD5- CD2- and CD7+ CD5+ CD2- lymphoblasts: studies
      on phenotype, genotype, and gene expression of myeloperoxidase, CD3 epsilon, and
      CD3 delta.
AB  - The gene expression of myeloperoxidase (MPO), CD3 epsilon, and CD3 delta
      molecules, the gene rearrangement of T-cell receptor (TCR) delta, gamma, and beta
      and immunoglobulin heavy (IgH) chain, and the expression of cell-surface antigens
      were investigated in seven cases of CD7+ CD5- CD2- and four cases of CD7+ CD5+
      CD2- acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts,
      which were negative for cytochemical myeloperoxidase (cyMPO). More mature T
      lineage blasts were also investigated in a comparative manner. In conclusion, the
      CD7+ CD5- CD2- blasts included four categories: undifferentiated blasts without
      lineage commitment, T-lineage blasts, T-/myeloid lineage blasts, and cyMPO
      negative myeloblasts. The CD7+ CD5+ CD2- blasts included two categories; T
      lineage and T-/myeloid lineage blasts. The 11 cases were of the germ-line gene
      (G) for TCR beta and IgH. Four cases were G for TCR delta and TCR gamma. The
      others were of the monoclonally rearranged gene (R) for TCR delta and G for TCR
      gamma or R for both TCR delta and TCR gamma. The expression or in vitro induction
      of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T
      cells, since it was observed in all 11 CD7+ CD5- CD2- and CD7+ CD5+ CD2-, and
      some CD7+ CD5+ CD2+ (CD3- CD4- CD8-) cases, but not in CD3 +/- CD4+ CD8+ or CD3+
      CD4+ CD8- cases. CD3 epsilon mRNA, but not CD3 delta mRNA, was detected in two
      CD7+ CD5- CD2- cases, while mRNA of neither of the two CD3 molecules was detected
      in the other tested CD7+ CD5- CD2- cases. In contrast, mRNA of both CD3 epsilon
      and CD3 delta were detected in all CD7+ CD5+ CD2- cases, indicating that CD7+ CD5
      CD2- blasts at least belong to T-lineage. The blasts of two CD7+ CD5- CD2- cases
      with entire germ-line genes and without mRNA of the three molecules (MPO, CD3
      epsilon, and CD3 delta) were regarded as being at an undifferentiated stage prior
      to their commitment to either T- or myeloid-lineage. The co-expression of the
      genes of MPO and CD3 epsilon in a CD7+ CD5- CD2- case MPO, CD3 epsilon, and CD3
      delta in a CD7+ CD5+ CD2- case suggested the presence of some overlapping phase
      for T- and myeloid-lineage commitment during immature stages of differentiation.
      This helps understand the conversion of some T-ALL/LBL cases to acute
      myeloblastic leukemia (AML).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7513946
TI  - Identification of three novel mutations in non-Ashkenazi Italian patients with
      muscle phosphofructokinase deficiency.
AB  - We have identified three novel mutations in four non-Ashkenazi Italian patients
      with muscle phosphofructokinase (PFK-M) deficiency (Tarui disease). Patient 1 was
      homozygous for an A-to-C substitution at the 3' end of intron 6 of the PFK-M
      gene, changing the consensus splice-junction sequence AG to CG. The mutation
      leads to activation of two cryptic splice sites in exon 7, resulting in one 5 bp-
      and one 12 bp-deleted transcript. An affected brother was also homozygous, and
      both parents were heterozygous, for the splice-junction mutation. Patient 2 was
      homozygous for a G-to-C substitution at codon 39, changing an encoded arginine
      (CGA) to proline (CCA). Patient 3 was heterozygous for an A-to-C substitution at
      codon 543, changing an encoded aspartate (GAC) to alanine (GCC); the PFK-M gene
      on the other allele was not expressed, but sequencing of the reported regulatory
      region of the gene did not reveal any mutation.

PMID- 7513947
TI  - Anencephaly: changes in prenatal detection and birth status, 1972 through 1990.
AB  - OBJECTIVE: We assessed at a large university hospital the effect of prenatal
      diagnosis on the birth of infants with anencephaly between 1972 and 1990. STUDY
      DESIGN: All 175 affected infants were identified by a postnatal Malformations
      Surveillance Program, which included stillborn infants and elective terminations
      in the second trimester. The affected infants were subdivided into those whose
      mothers had always planned delivery at this hospital (nontransfers) and those
      whose mothers had planned delivery elsewhere but were transferred after the
      prenatal detection of the fetal abnormality (transfers). RESULTS: In the 1970s
      half the infants were anencephaly were born alive; the average gestational age
      was 35.6 weeks, and only a few were diagnosed prenatally. By 1988 to 1990 all
      affected infants were diagnosed either by prenatal ultrasonography or as the
      result of maternal serum alpha-fetoprotein screening; the parents elected to
      terminate the pregnancies, and the average gestational age was 19.6 weeks.
      CONCLUSION: Prenatal detection and the selection by parents of the option of
      elective termination of pregnancy has altered significantly the birth status of
      infants with anencephaly since 1972.

PMID- 7513949
TI  - Differential cellular expression of cystic fibrosis transmembrane regulator in
      human reproductive tissues. Clues for the infertility in patients with cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is characterized by a wide spectrum of clinical
      manifestations, including reproductive problems. Practically all males affected
      by the disease are infertile due to azoospermia associated with pathology of the
      male ducts, whereas females with CF have reduced fertility. To study the
      mechanism of reproductive pathology in CF patients, we analyzed the levels and
      localization of expression of the cystic fibrosis transmembrane regulator (CFTR)
      gene in relevant postnatal tissues. Significant expression was detected in the
      epithelium of the epididymis and vas deferens. Minimal expression, not associated
      with specific cell types, was seen in the mature testis. In female genitalia,
      variable levels of expression were seen in the cervical epithelium and fallopian
      tube. The endometrial epithelium and glands expressed CFTR at high levels only
      after puberty. No expression was seen in ovaries. Deficient secretory function of
      CFTR in males but not in females may lead to organ damage probably as a
      consequence of excessive concentration of viscid luminal contents.

PMID- 7513948
TI  - Role of leukocyte adhesion molecules in lung and dermal vascular injury after
      thermal trauma of skin.
AB  - Acute second degree thermal injury of rat skin involving 25 to 30% total body
      surface of anesthetized rats results at 4 hours in evidence of vascular injury
      both locally (in skin) and remotely (involving lung). The neutrophil dependency
      for both types of injury has now been established. Monoclonal antibodies to
      various adhesion molecules have been used to define the requirements for these
      molecules in the development of vascular injury. In dermal vascular injury, a
      requirement for Mac-1 (CD11b/CD18) but not for leukocyte function-associated
      antigen-1 (LFA-1, CD11a/CD18) has been established. In this model requirements
      have also been demonstrated for intercellular adhesion molecule-1 (ICAM-1) and E-
      and L-selectin but not for very late arising antigen-4 (VLA-4) or P-selectin.
      With respect to lung vascular injury, dual requirements for both leukocyte
      function-associated antigen-1 and Mac-1 were found as well as for ICAM-1 and E-
      and L-selectin but not for VLA-4 and P-selectin. In the lung, there was a close
      correlation between neutrophil content of the tissue (as assessed by
      myeloperoxidase) and the effects of protective interventions (directed against
      blocking of adhesion molecules). These data emphasize the roles of beta 2
      integrins, selectins (L and E), and ICAM-1 in events that lead to neutrophil
      mediated vascular injury of dermis and lung after thermal trauma to skin.

PMID- 7513950
TI  - Endothelial and smooth muscle cells express leukocyte adhesion molecules
      heterogeneously during acute rejection of rabbit cardiac allografts.
AB  - Interactions of leukocytes with vascular wall cells figure prominently in acute
      rejection and development of vascular occlusive disease after cardiac
      transplantation. To investigate the time course and distribution among different
      types of vessels of expression of endothelial leukocyte adhesion molecules,
      issues difficult to address in humans, we studied heterotopic transplants of
      Dutch-Belted rabbit hearts into New Zealand white recipients without
      immunosuppression (average time to graft failure 8.2 +/- 0.4 days). We found
      constitutive expression of vascular cell adhesion molecule-1 (VCAM-1) and
      intercellular adhesion molecule-1 (ICAM-1) by coronary arterial endothelium in
      normal rabbits, whereas myocardial capillaries and the endocardial lining cells
      showed little or no expression of VCAM-1. VCAM-1 expression increased within 1
      day after transplantation on the endothelium of the transplanted aorta and
      endocardium and on myocardial microvascular endothelial cells. ICAM-1 expression
      increased remarkably on all endothelia studied from 2 to 8 days after
      transplantation. Adhesion molecule expression on coronary artery endothelial
      cells also increased during severe allograft rejection (from a histological score
      of 1.7 +/- 0.6 pretransplant to 4.8 +/- 0.2 8 days after transplant for VCAM-1
      and from 0.9 +/- 0.6 to 4.4 +/- 0.3 for ICAM-1, n = 43 arteries in 5 animals,
      mean +/- SD). In addition, coronary artery and aortic smooth muscle cells also
      showed induction of VCAM-1 and ICAM-1 8 days after transplant. We conclude that
      endothelial activation in a transplanted organ can occur rapidly and varies among
      microvascular, endocardial, and coronary artery endothelial cells, a point
      germane to the interpretation of endomyocardial biopsies. Augmented expression of
      adhesion molecules precedes temporally leukocyte accumulation in vessels. In
      addition, our finding of activation of coronary artery smooth muscle cells during
      acute rejection suggests that such episodes may contribute to the development of
      accelerated coronary arteriosclerosis.

PMID- 7513951
TI  - Increase in the adhesion molecule P-selectin in endothelium overlying
      atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1.
AB  - P-selectin (GMP-140) is an adhesion molecule present within endothelial cells
      that is rapidly translocated to the cell membrane upon activation, where it
      mediates endothelial-leukocyte interactions. Immunohistochemical analysis of
      human atherosclerotic plaques has shown strong expression of P-selectin by the
      endothelium overlying active atherosclerotic plaques. P-selectin is not, however,
      detected in normal arterial endothelium or in endothelium overlying inactive
      fibrous plaques. Color image analysis was used to quantitate the degree of P
      selectin expression in the endothelium and demonstrates a statistically
      significant increase in P-selectin expression by atherosclerotic endothelial
      cells. Double immunofluorescence shows that some of this P-selectin is expressed
      on the luminal surface of the endothelial cells. Previous work has demonstrated a
      significant up-regulation in the expression of the intercellular adhesion
      molecule-1 in atherosclerotic endothelium and a study on the expression of
      intercellular adhesion molecule-1 and P-selectin in atherosclerosis shows a
      highly positive correlation. These results suggest that the selective and
      cooperative expression of P-selectin and intercellular adhesion molecule-1 may be
      involved in the recruitment of monocytes into sites of atherosclerosis.

PMID- 7513952
TI  - Dietary protein-induced renal growth: correlation between renal IGF-I synthesis
      and hyperplasia.
AB  - Insulin-like growth factor I (IGF-I) and IGF binding protein 1 (IGFBP-1) mRNAs
      are colocalized in the medullary thick ascending limb (MTAL) of the rat nephron,
      a segment that undergoes selective growth in response to elevated dietary
      protein. In the present study, rats were fed isocaloric diets containing variable
      protein content (6-40%) for 1-7 days, and changes in fractional renal weight,
      MTAL length, and regional DNA synthesis were assayed and compared with local
      changes in IGF-I/IGFBP-1 mRNAs, as determined by quantitative in situ
      hybridization. Rats switched to high-protein diets demonstrated increased IGF-I
      and decreased IGFBP-1 mRNA levels in MTALs, whereas those switched to low protein
      showed inverse changes. The increase in renal IGF-I mRNA was maximal at 2 days
      and was closely paralleled by significant increases in fractional renal weight,
      DNA synthesis, and MTAL length. Similar changes were seen in vasopressin
      deficient Brattleboro and growth hormone (GH)-deficient dwarf rats in response to
      high-protein diets, suggesting that the effects of dietary protein in this model
      are not mediated by vasopressin or GH. The close spatial and temporal correlation
      between changes in renal IGF-I expression and changes in regional growth
      parameters strongly supports a role for locally produced IGF-I in the induction
      of protein-induced renal growth.

PMID- 7513953
TI  - Mechanism of sodium hyperabsorption in cultured cystic fibrosis nasal epithelium:
      a patch-clamp study.
AB  - Transepithelial Na+ absorption is increased two to three times in cystic fibrosis
      (CF) compared with normal (NL) airway epithelia. This increase has been
      associated with a higher Na+ permeability of the apical membrane of airway
      epithelial cells. Because Na+ absorption is electrogenic and abolished by
      amiloride, Na+ channels are thought to dominate the apical membrane Na+
      permeability. Three Na+ channel-related mechanisms may explain the increase in
      apical Na+ permeability in CF cells: increased number of channels, increased
      single-channel conductance, and increased single-channel open probability. We
      compared the properties of Na(+)-permeable channels in the apical membrane of
      confluent preparations of human NL and CF nasal epithelial cells cultured on
      permeable supports. Na(+)-permeable channels were studied using the patch-clamp
      technique in the excised inside-out and cell-attached configurations. The same
      types of Na(+)-permeable channels were recorded in CF and NL cells. In excised
      patches, nonselective (Na+/K+) cation channels were recorded, and no differences
      between CF and NL were found in the properties, incidence, single-channel
      conductance, and single-channel open probability. In cell-attached patches,
      channels with a higher Na+ vs. K+ selectivity dominated. There was no difference
      between CF and NL cells in the incidence (18.8 vs. 21.4%, respectively) and
      conductance (17.2 +/- 2.8 vs. 21.4 +/- 1.5 pS, respectively) of Na(+)-permeable
      channels. However, the open probability was higher in CF cells compared with NL
      cells (30.0 +/- 3.4%, n = 6, vs. 15.0 +/- 3.9%, n = 13; P < 0.05). We conclude
      that, in CF nasal epithelial cells, the increase in Na+ permeability of the
      apical membrane results from an increase in the open probability of Na(+)
      permeable channels in the apical membrane.

PMID- 7513954
TI  - Extrarenal tissue distribution of CHIP28 water channels by in situ hybridization
      and antibody staining.
AB  - This study is an extension of in situ hybridization experiments showing
      expression of mRNA encoding CHIP28 in selected epithelial or endothelia in
      spleen, colon, lung, and eye (H. Hasegawa, R. Zhang, A. Dohrman, and A. S.
      Verkman. Am. J. Physiol. 264 (Cell Physiol. 33): C237-C245, 1993). Additional
      tissues from rat were screened by in situ hybridization, and tissues from rat and
      humans were stained with a polyclonal anti-CHIP28 antibody. Northern blot showed
      the 2.8-kilobase mRNA encoding CHIP28 in kidney, lung, and heart. In situ
      hybridization showed strong hybridization in epithelial cells in choroid plexus,
      iris, ciliary body, and lens and in epithelial and subepithelial layers of
      trachea. Except for colonic crypts, specific hybridization was not observed in
      the gastrointestinal tract, liver, thyroid gland, and muscle. Immunoblot of
      tissues from exsanguinated rats showed immunoreactive CHIP28 protein in kidney,
      lung, trachea, and heart. In fixed frozen rat and/or human tissues, the anti
      CHIP28 antibody stained epithelial cells in kidney proximal tubule and thin limb
      of Henle, lung alveolus, bronchial mucosa and glands, choroid plexus, ciliary
      body, iris, lens surface, colonic crypt, sweat gland, pancreatic acini,
      gallbladder epithelium, and placental syncytial trophoblast cells. Endothelial
      cells were stained in many tissues. These studies indicate a wide and selective
      CHIP28 tissue distribution, suggesting an important role for CHIP28 in fluid
      transport. The absence of CHIP28 in many nonrenal membranes believed to be water
      permeable suggests the existence of non-CHIP28 water transporters.

PMID- 7513955
TI  - Acinar zonation of the hormonal regulation of cytosolic aspartate
      aminotransferase in the liver.
AB  - The zonation of the expression and regulation of the cytosolic aspartate
      aminotransferase (cAspAT) mRNAs in the liver acinus was investigated in diabetic
      and/or adrenalectomized rats. Dexamethasone increased cAspAT activity two- to
      threefold alone and up to sixfold in combination with streptozotocin-induced
      diabetes. Northern blot analysis showed that the cAspAT mRNAs were increased by
      those treatments; the effect of streptozotocin was reversed by the administration
      of insulin. In situ hybridization experiments showed that basal cAspAT mRNAs were
      uniformly distributed within the liver acinus. However, cAspAT mRNAs were induced
      by glucocorticoids specifically in the periportal zone and by streptozotocin in a
      larger area including the periportal and intermediary zone. The alpha 2u-globulin
      mRNAs which are specifically expressed in the perivenous hepatocytes are also
      induced by glucocorticoids in this zone, suggesting that the specific regulation
      of the cAspAT gene by glucocorticoids in the periportal zone is not due to the
      absence of functional glucocorticoid receptors in the other zones. We conclude
      that the regulation of the cAspAT housekeeping gene is zone specific in the
      liver. Furthermore, this zonation depends on the gene and on the type of hormonal
      or pharmacological treatment.

PMID- 7513956
TI  - Ultrastructural localization of nitric oxide synthase in canine small intestine
      and colon.
AB  - The ultrastructural distribution and subcellular localization of nitric oxide
      synthase (NOS) immunoreactivity and its possible colocalization with vasoactive
      intestinal polypeptide (VIP) and substance P in the muscularis externa in canine
      ileum and colon were studied by using polyclonal antisera raised against VIP,
      substance P, and cerebellar NOS. Immunogold staining, with or without silver
      enhancement, was carried out directly on ultrathin sections using single and two
      faced double immunogold methods. NOS immunoreactivity was observed in nerve
      profiles in myenteric plexus and circular muscle layer. Immunoreactivity was
      occasionally detected in smooth muscle cells and interstitial cells of Cajal. The
      double immunostaining revealed NOS and VIP in the same nerve varicosities but
      never in the same organelles. NOS was localized in electron-dense material of
      undetermined nature, whereas VIP was associated with large granular vesicles.
      Substance P and NOS were never found in the same nerves. These results indicate
      that NOS is present in the enteric nerves containing VIP but in different
      organelles and that nitric oxide release probably does not occur by an exocytotic
      mechanism.

PMID- 7513957
TI  - Canine, human, and rat plasma insulin responses to galanin administration:
      species response differences.
AB  - Previous studies demonstrated that porcine galanin is a potent inhibitor of
      insulin secretion in many species but fails to alter human insulin secretion. To
      resolve whether this discrepancy was due to the use of a heterologous peptide or
      to a true species response difference, we studied the effect of a synthetic
      replicate of human galanin on glucose-stimulated insulin secretion in rats, dogs,
      and humans. On administration into rats, human and rat galanin significantly
      inhibited glucose-induced insulin responses to a similar degree. Similarly,
      porcine and human galanin significantly elevated canine plasma glucose and
      inhibited canine plasma insulin responses. In contrast, plasma glucose and
      insulin responses to glucose administration in humans were unaltered by the
      addition of human galanin at or above the maximum effective dose employed in
      dogs. Possible effects of galanin administration were seen on human glucagon and
      pancreatic polypeptide responses to glucose at the highest dose of human galanin
      infused. We conclude that galanin probably does not play a major role in
      modulating human beta-cell function.

PMID- 7513958
TI  - Role of elongation factor 2 in regulating peptide-chain elongation in the heart.
AB  - Cardiac muscles of experimentally induced diabetic rats show a progressive
      decrease in the rate of protein synthesis. The decline in protein synthesis is
      associated with decreases in both the number and efficiency of cardiac ribosomes.
      In hearts from 48 h diabetic rats, the decrease in protein synthesis was
      accounted for solely by a 28% reduction in the ribosome content. In contrast, the
      inhibition of protein synthesis in hearts from 72 h diabetic rats resulted from a
      reduction in both the ribosome content (28%) and the translational efficiency
      (30%). The decreased translational efficiency was not associated with an increase
      of RNA in ribosomal subunits, indicating the defect resulted from an inhibition
      of peptide-chain elongation/termination. Diabetes of 72 h duration resulted in a
      37% inhibition in the rate of peptide-chain elongation. The decreased rate of
      peptide-chain elongation was associated with a 66% reduction in the amount of
      elongation factor 2 (EF-2). Treatment of diabetic rats with insulin for 3 days
      was sufficient to reverse the effects of 72 h diabetes on protein synthesis, RNA
      content, and translational efficiency. Also, insulin therapy increased the EF-2
      content of diabetic rats to control values. These studies suggest that decreased
      EF-2 content is a molecular mechanism for the impaired rates of peptide-chain
      elongation in diabetes.

PMID- 7513959
TI  - Endotoxin-induced ileal mucosal hyperpermeability in pigs: role of tissue
      acidosis.
AB  - Administration of lipopolysaccharide (LPS) to experimental animals leads to
      diminished mesenteric perfusion, increased ileal mucosal [H+] , and increased gut
      epithelial permeability to hydrophilic solutes. We sought to determine whether
      these phenomena are causally related. Experiments were performed in anesthetized
      pigs. Permeability was assessed by measuring the plasma-to-lumen clearance of
      fluorescein isothiocyanate dextran (4,000 Da; FD-4) by a segment of ileum
      perfused with Ringer lactate solution. Mucosal perfusion (Qmuc) and [H4+] were
      estimated using laser-Doppler flowmetry and tonometry, respectively. In an
      initial series of experiments, we showed that mucosal permeability was linearly
      correlated with mucosal [H+] in animals subjected to graded degrees of
      mechanically induced mesenteric ischemia (n = 14, R2 = 0.58, P < 0.002) or
      injected with graded doses of LPS (n = 11, R2 = 0.93, P < 0.0001). In a second
      series of experiments, we induced mucosal acidosis in normal pigs by mechanical
      ventilation with either a hypoxic (n = 7) or a hypercapnic (n = 5) gas mixture.
      In both groups, ileal mucosal permeability to FD-4 increased significantly (P <
      0.05), although transmesenteric release of lactate increased significantly only
      in the hypoxic group. Qmuc was unchanged in both groups. These data suggest that
      mucosal acidosis, even in the absence of tissue ischemia or hypoxia, increases
      intestinal permeability to a macromolecular hydrophilic solute. Tissue acidosis
      may be an important factor contributing to LPS-induced gut mucosal
      hyperpermeability.

PMID- 7513960
TI  - Effect of nonsteroidal anti-inflammatory drugs on LFA-1 and ICAM-1 expression in
      gastric mucosa.
AB  - Leukocyte adhesion to the endothelium appears to play an important role in
      gastric injury. This study aimed to develop immunohistochemical staining
      techniques to investigate the distribution and sequence of expression of both
      leukocyte [lymphocyte function associated antigen 1 (LFA-1)] and endothelial
      [intracellular adhesion molecule 1 (ICAM-1)] adhesion molecules in the mucosa
      after treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). In control
      rats there were 803 +/- 72 LFA-1-stained cells/mm2 in the deep mucosa, 134 +/- 32
      cells/mm2 in the superficial mucosa, and 6.4 +/- 1.2 ICAM-1-stained blood
      vessels/mm2 in the total mucosa. The number of ICAM-1-stained blood vessels in
      the mucosa increased significantly after 30 min of treatment with intragastric
      aspirin (30 mM; 25.2 +/- 7.2/mm2, P < 0.01) and indomethacin (20 mg/kg; 20.7 +/-
      4.4/mm2, P < 0.01) before any appreciable mucosal damage was evident. This
      increase was reversed by treatment with misoprostol (100 micrograms/kg) in both
      aspirin- (7.6 +/- 1.7/mm2, P < 0.01) and indomethacin-treated animals (10.7 +/-
      2.6/mm2, P < 0.05). There was no significant increase in LFA-1-positive cells
      until 60 min of NSAID treatment. We conclude that the adhesion molecules LFA-1
      and ICAM-1 are expressed in the normal gastric mucosa and that the number of ICAM
      1-stained blood vessels increase rapidly after NSAID treatment. This increase in
      ICAM-1 expression may be associated with an inhibition of prostaglandin synthesis
      by NSAIDs. These results provide further support for the role of early vascular
      changes in NSAID gastropathy.

PMID- 7513961
TI  - Regulation of cation channels in liver cells by intracellular calcium and protein
      kinase C.
AB  - The regulation of Ca(2+)-permeant cation channels in HTC hepatoma cells was
      investigated using patch clamp and fluorescence techniques. In intact cells,
      exposure to nucleotide analogues ATP, uridine 5'-triphosphate (UTP), and
      adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) caused transient opening of
      channels with linear conductances of approximately 18 and approximately 28 pS.
      Channels were permeable to Na+, K+, and Ca2+ and carried inward (depolarizing)
      current at the resting potential. Exposure to thapsigargin to increase cytosolic
      Ca2+ concentration ([Ca2+]i) opened similar channels, suggesting that opening is
      stimulated by a rise in [Ca2+]i. In subconfluent monolayers, ATP increased
      [Ca2+]i with half-maximal effects at approximately 7.4 microM; at 10(-4) M, the
      peak increase in [Ca2+]i was ATP > UTP > ATP gamma S >> 2-methylthioadenosine 5'
      triphosphate, alpha,beta-methyleneadenosine 5'-triphosphate, and adenosine. The
      relative potency suggests that the effects are mediated by 5'-nucleotide
      receptors. In excised inside-out patches, channels were not activated by myo
      inositol 1,4,5-trisphosphate (50-100 microM) or myo-inositol 1,3,4,5
      trisphosphate (20 microM) but opened after increases in Ca2+ to greater than
      approximately 250 nM, consistent with a direct role for Ca2+ in channel opening.
      In intact cells, channel opening was followed by a prolonged refractory period.
      Protein kinase C appears to contribute by inhibition of the ATP-stimulated
      [Ca2+]i response and by direct inhibitory effects on the channel. These findings
      indicate that extracellular ATP leads to modulation of liver cell cation channels
      through activation of 5'-nucleotide receptors and are consistent with a model in
      which transient opening of channels is stimulated by a rise in [Ca2+]i and
      subsequent closure is mediated by protein kinase C-dependent pathways.

PMID- 7513962
TI  - Stationary red blood cells induce a negative charge on mucosal capillary
      endothelium.
AB  - Previous studies on Wistar-Furth rat intestinal mucosal capillaries show a
      variation in extent of binding of cationized ferritin (CF) to the endothelial
      surface. Three possible causes of this variation were investigated: 1) location
      of capillaries along the intestine, 2) time after feeding, and 3) effect of short
      term hemostasis. In studies 1 (5 rats) and 2 (22 rats), the intestinal
      circulation was perfused with CF and perfusion fixed for electron microscopy.
      Observation of capillaries demonstrated that variation in CF binding could not be
      explained by factors 1 or 2. In study 3, capillaries on the mucosal surface were
      viewed using epifluorescent microscopy and were perfused with fluorescein
      isothiocyanate (FITC)-labeled CF. Initial perfusion produced no binding, but
      perfusion after 2 or 10 min of stasis gave extensive binding (19 rats). Stasis
      with red blood cells in saline (6 rats) or with hemoglobin solution (6 rats) gave
      similar results, but stasis with saline, platelet-rich plasma, or red cell ghosts
      in saline did not produce binding (8, 7, and 5 rats, respectively). Hemoglobin
      injected into the circulation without stasis also caused binding of FITC-CF, but
      not if the nitric oxide (NO) donor, SIN-1, was injected simultaneously. Stasis
      with saline containing the NO inhibitor, NG-nitro-L-arginine methyl ester
      produced some binding of FITC-CF (5 rats). We conclude that intestinal mucosal
      capillaries do not express a net negative surface charge under brisk flow
      conditions, but charge is quickly generated after blood stasis. It is possible
      that when red blood cells are stationary, hemoglobin may trap NO that otherwise
      might neutralize the negatively charged groups.

PMID- 7513963
TI  - Expression of cystic fibrosis transmembrane conductance regulator in a model
      epithelium.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl- channel
      regulated by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent
      phosphorylation and by intracellular nucleotides. The function of CFTR, like
      other recombinant ion channels, has generally been studied in single cells using
      voltage-clamp techniques. However, because CFTR is normally located in the apical
      membrane of epithelia we wanted to develop a system to study the function of
      recombinant CFTR expressed in an epithelium. We chose Fischer rat thyroid (FRT)
      epithelia for two reasons. First, when grown on permeable filter supports, FRT
      cells form polarized epithelia with a high transepithelial resistance. Second,
      they have no endogenous cAMP-regulated Cl- channels in their apical membrane. We
      expressed CFTR in FRT epithelia either transiently, using recombinant vaccinia
      virus, or stably, using a retrovirus. To measure apical membrane Cl- currents, we
      permeabilized the basolateral membrane to monovalent ions with nystatin and
      imposed a large transepithelial Cl- concentration gradient. cAMP agonists
      stimulated apical membrane Cl- currents in FRT epithelia infected with wild-type
      CFTR (vTF-CFTR) but not in FRT epithelia infected with either control virus (vTF7
      3) or CFTR containing the delta F508 mutation (vTF-delta F508). These Cl-
      currents had properties similar to those of cAMP-activated Cl- currents in cells
      expressing endogenous or recombinant CFTR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513964
TI  - The beta 2-adrenergic receptor agonist formoterol reduces microvascular leakage
      by inhibiting endothelial gap formation.
AB  - beta 2-Adrenergic receptor agonists inhibit the increase in vascular permeability
      produced by a variety of inflammatory mediators. The anti-edema effect of beta 2
      agonists is assumed to result from a direct action on endothelial cells, but such
      a mechanism has not been demonstrated in vivo. The aim of this study was to
      determine whether beta 2-agonists exert their anti-edema effect by inhibiting the
      formation of endothelial gaps at sites of plasma leakage. Vascular permeability
      in the rat trachea was increased by electrical stimulation of the vagus nerve or
      by intravenous injection of substance P (5 micrograms/kg iv). Plasma leakage was
      quantified by using Monastral blue and Evans blue as tracers. Endothelial gaps
      were made visible for light microscopy by staining the borders of endothelial
      cells with silver nitrate. The experiments showed that the selective beta 2
      agonist formoterol, which is known to have anti-edema effects, reduced the plasma
      leakage produced by either stimulus. The effect was dose dependent, with a
      formoterol dose of 10 micrograms/kg iv producing maximal reduction of Monastral
      blue leakage (64 +/- 14%). The amounts of extravasation of Monastral blue and
      Evans blue were closely correlated (r2 = 0.76, P < 0.01). After the injection of
      substance P, there were 15.3 +/- 1.0 gaps/endothelial cells in postcapillary
      venules of vehicle-pretreated rats, but only 5.0 +/- 0.2 gaps/cell in formoterol
      pretreated (10 micrograms/kg iv) rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513965
TI  - Acute hypoxia causes membrane depolarization and calcium influx in fetal
      pulmonary artery smooth muscle cells.
AB  - Changes in oxygen tension in the perinatal period contribute to high pulmonary
      vascular tone in the fetus and the decline in resistance that occurs at birth.
      Distal pulmonary artery smooth muscle cells (PASMC) isolated from late-gestation
      ovine fetuses respond to acute hypoxia with an increase in cytosolic calcium
      concentration ([Ca2+]i) dependent on Ca2+ entry. The purpose of this study is to
      determine 1) whether acute hypoxia results in PASMC membrane depolarization, 2)
      whether Ca2+ entry was through voltage-operated calcium channels (VOCC), 3) the
      contribution of Ca(2+)-induced Ca2+ release (CICR) to the hypoxic response, and
      4) whether a subset of K+ channels might serve as oxygen sensors in fetal PASMC.
      We used microfluorimetry on subconfluent monolayers of PASMC in primary culture
      loaded with either a membrane potential-sensitive dye, bis(1,3-dibutylbarbituric
      acid) trimethine oxonol (DiBAC4; DPASMC), to estimate membrane potential, or the
      Ca(2+)-sensitive fluorophore, fura 2, to measure [Ca2+]i. Hypoxia increased
      fluorescence from PASMC loaded with DiBAC4, consistent with membrane
      depolarization. Verapamil (an inhibitor of VOCC) attenuated, and BAY K 8644 (a
      VOCC facilitator) potentiated, the hypoxia-induced increase in [Ca2+]i,
      respectively. The hypoxic response was transient after treatment with ryanodine
      (10(-7) M), a blocker of calcium release from intracellular stores. Charybdotoxin
      (10(-7) M), an inhibitor of Ca(2+)-activated K+ channels, almost doubled [Ca2+]i,
      whereas glibenclamide (10(-5) M), an ATP-sensitive K(+)-channel antagonist, had
      no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513966
TI  - Colorectal counterpart of gastric depressed adenoma. A comparison with flat and
      polypoid adenomas with special reference to the development of pericryptal
      fibroblasts.
AB  - The histological features of 28 depressed adenomas (DAs) were compared with those
      of 40 flat adenomas (FAs) without a central depression and those of 29 polypoid
      adenomas (PAs), with special reference to the development of pericryptal
      fibroblasts (PCFs), using immunohistochemical staining for muscle-specific actin
      (HHF-35). The DAs were composed of a crowded collection of adenomatous tubules
      with smaller diameters than those of the PAs. With regard to PCF development, the
      DAs had poorly developed PCFs; PCF (-), (+), and (++) numbered 12 (43%), 16
      (57%), and 0 (0%), respectively. On the other hand, the nondepressed adenomas
      (PAs and FAs) had well-developed PCF; PCF (-), (+), and (++) numbered 5 (7%), 35
      (51%), and 29 (42%), respectively. In addition, the number of PCFs seemed to
      decrease in the sequence of PAs, followed by FAs and DAs. According to our
      results, the DAs had a characteristic histological architecture together with
      poorly developed PCFs features, which distinguished them from the PAs. In
      conclusion, the depressed adenomas were considered a subtype of the flat
      adenomas. The depletion of PCFs seems to correlate with the depressed growth of
      the adenoma.

PMID- 7513967
TI  - The role of palliative pelvic exenteration.
AB  - A retrospective review was made of pelvic exenterative procedures performed over
      a 45-month period at a single institution for symptom palliation in 35 patients
      with previously treated pelvic cancers (21 colorectal, 9 urinary, 5 gynecologic).
      Preexenterative treatment and nutritional and performance status were determined.
      The impact of the disease and the symptoms on quality of life both before and
      after exenteration was evaluated. Symptoms leading to exenteration included pain
      (n = 12), bleeding (n = 11), fistula (n = 7), or obstruction (n = 6) and were
      present for a median duration of 12 months before surgery. Procedures included 11
      total, 13 anterior, and 11 posterior exenterations, with 17 extended resections.
      Operative mortality was 3% and overall morbidity was 47%. Quality of life
      improved in 88% of patients after exenteration. Median overall survival was 20
      months, and 43% of patients were still alive after a minimum of 16 months of
      follow-up.

PMID- 7513968
TI  - Treatment of head-and-neck carcinoma with noncurative intent.

PMID- 7513969
TI  - [Interactions of intravenous anesthetics with human CNS ion channels.
      Electrophysiologic studies with a new type of voltage clamp technique].
AB  - Despite a widespread approach to explain the molecular mechanisms of anaesthetic
      agents, the complex state of "general anaesthesia" is still not completely
      understood. Voltage-activated sodium channels from human brain cortex served as a
      model membrane protein to investigate anaesthetic drug-protein interactions using
      a novel electrophysiological voltage-clamp technique. Sodium channels are already
      well-characterized important integral membrane proteins responsible for the
      generation of the fast-propagated action potential and thus are vital components
      for neuronal signal integration and cell communication. In order to elucidate the
      molecular interactions of intravenous anaesthetics with single human brain sodium
      channels, representative compounds of four different clinical intravenous
      anaesthetic groups were used to correlate different types of clinical anaesthesia
      with differential anaesthetic effects on the molecular level. METHODS. Single
      sodium channels from human brain cortex were incorporated into artificial
      phospholipid bilayers and studied under our standard experimental conditions
      (Electrolyte solution: 500 mM NaCl, 10 mM HEPES, pH 7.4, Temp. 22-25 degrees C)
      with an electrophysiological voltage-clamp technique. In the presence of a
      channel activator (1 microM batrachotoxin) single-channel characteristics
      (fractional open time, single-channel conductance and amplitude, steady-state
      activation behaviour) were characterized for control conditions and in the
      presence of various doses of four different anaesthetic agents (pentobarbital,
      propofol, ketamine, midazolam). RESULTS. During control measurements the
      investigated human brain sodium channels showed stable and reproducible
      characteristics on the range expected for batrachotoxin-modified sodium channels
      in bilayers. After completion of the control measurement the effects of the four
      different general anaesthetics pentobarbital, propofol, ketamine and midazolam
      were investigated on the same control sodium channels. All four substances
      demonstrated a blocking effect of sodium channel conductance (pentobarbital: K50:
      concentration for 50% block of the maximal conductance block: 0.69 mM; blockmax:
      maximal conductance block (%): 100%; propofol: K50: 0.02 mM, blockmax: 28%;
      ketamine: K50: 1.1 mM, blockmax: 71%; midazolam: K50: 0.52 mM, blockmax: 100%).
      Furthermore, a destabilization of the steady-state activation process could be
      demonstrated. These effects were dose dependent, but only pentobarbital and
      propofol demonstrated these effects at or near clinically relevant serum
      concentrations. DISCUSSION: At the clinical level, "general anaesthesia" is a
      highly complex phenomenon. Similarly, anaesthetics may demonstrate a
      multimechanistic mode of action also at the molecular level. In this study all
      four investigated anaesthetic compounds interacted with at least two primary
      sodium channel functions, leading to a voltage-independent reduction of the
      fractional channel open time and an interaction with the steady-state activation
      behaviour, respectively. The effects of pentobarbital and propofol were
      detectable at concentrations within the range of serum concentrations achieved
      during clinical anaesthesia, whereas ketamine and midazolam demonstrated
      qualitatively similar effects exceeding this range 10- to 50-fold. Thus, the
      human brain sodium channel might serve as a molecular target only for
      pentobarbital and propofol. This suggests that different types of clinical
      anaesthesia may correlate with differential actions of anaesthetics on the
      molecular level.

PMID- 7513970
TI  - Detection and quantitation of cell-cell electrofusion products by flow cytometry.
AB  - A cytometric method for detecting and quantitating hybrid cells that resulted
      from cell-cell electrofusion was developed. Cells from two different lines and
      two vital fluorescent dyes were used in conjunction with a flow cytometer to
      demonstrate the method. Each dye was used to stain one cell type prior to
      electrofusion. Hybrid cells exhibited dual fluorescence while unfused cells
      retained their single fluorescence. Flow cytometry was used to detect dual
      fluorescing hybrid cells that resulted from electrofusion. Fluorescent microscopy
      was used to confirm that 92% of the cytometrically detected cells were hybrids.
      Flow cytometry was also used to quantitatively show differences in hybrid yields
      for samples fused using different electrical conditions. These results
      demonstrate that the method can be used for detection and quantitation of
      electrofusion products. The methodologies presented are not specific to the cell
      types used; they can be adapted for use with other cell types.

PMID- 7513971
TI  - A method for analysis of gene expression patterns.
AB  - mRNA can be copied into cDNA with the use of reverse transcriptase so that the
      relative abundance of individual mRNAs is reflected in the cDNA product. With
      further manipulation a replica of the mRNA expression pattern can be duplicated
      into a radioactive double-stranded DNA probe. DNA from a series of genes inserted
      into plasmids can be fixed to a membrane using a slot blot manifold and probed
      with the RNA-derived DNA probe. The intensity of the hybridization signal for a
      given gene is a result of its relative abundance in the RNA-derived DNA probe.
      Quantitation can be achieved through the use of housekeeping genes as baseline
      monitors. Inclusion of vector sequences can negate any spurious hybridization to
      vector rather than insert sequences. We have successfully used this method to
      obtain gene expression patterns for RNA isolated from diverse sources including
      rodent tissues, various cell lines, and Drosophila and Caenorhabditis elegans
      samples. Northern blots have verified the results obtained. The pattern of
      expression of many genes can be determined from as little as 10 micrograms of
      total RNA, making this method ideally suited for studies in which RNA is rare or
      in short supply.

PMID- 7513972
TI  - Reducing-end modification of N-linked oligosaccharides with tyrosine.
AB  - The N-linked oligosaccharides from bovine fetuin were purified using newly
      developed preparative purification methodology. N-linked oligosaccharides were
      released from tryptic glycopeptides utilizing N-glycosidase F on the 5-g scale.
      Selective desialylation with neuraminidase from Clostridium perfringens resulted
      in the formation of a mono-sialyl-oligosaccharide and asialo-oligosaccharides.
      The reducing ends of the oligosaccharides were converted to the glycosylamine and
      reacted with the N-hydroxysuccinimide ester of Boctyrosine. The tyrosinated
      oligosaccharides were resolved into individual peaks on RP-HPLC and then
      characterized by proton NMR and FAB-MS. A single asialo-triantennary, an asialo
      biantennary, and a mono-sialyl-triantennary oligosaccharide were recovered in
      good yield. Each product contained a single Boc-Tyr residue attached to the
      reducing-end GlcNAc residue through a beta-glycosylamide linkage. The procedure
      was utilized to isolate multi-micromole quantities of oligosaccharides from gram
      quantities of glycoprotein, thus providing a new route to purify large quantities
      of N-linked oligosaccharides which contain a terminal tyrosine residue. The
      tyrosinated oligosaccharides are valuable glycoconjugate ligands which contain a
      chromophore that absorbs at 280 nm and has sufficient hydrophobicity to
      facilitate RP-HPLC separations. Furthermore, this group can be deprotected by
      removal of Boc to reveal a primary amine suitable for further derivatization and
      can also be radioiodinated for tracking during biological experiments.

PMID- 7513973
TI  - Enzymatic synthesis of folate and antifolate polyglutamates with Escherichia coli
      folylpolyglutamate synthetase.
AB  - Escherichia coli folylpolyglutamate synthetase was used to synthesize micromole
      quantities of polyglutamyl conjugates of folic acid, methotrexate, and other
      analogs of folic acid. The products of the enzymatic reactions were purified by
      semipreparative C18 HPLC. The position of each amide linkage (gamma or alpha
      carboxyl) in the polyglutamated products was determined by limited and exhaustive
      hydrolyses with hog kidney folylpolyglutamate hydrolase and with yeast
      carboxypeptidase Y. Under standard reaction conditions, the E. coli enzyme added
      up to five glutamyl residues to each monoglutamated substrate, primarily at the
      gamma carboxyl position. Thus, an enzyme which naturally adds only two glutamates
      to naturally occurring folates can be used synthetically to make higher
      polyglutamates of a wide range of synthetic substrates. The products of the
      reactions are valuable tools for the study of the metabolism of antifolate drugs
      as well as metabolic reactions involving folate cofactors.

PMID- 7513975
TI  - A simple device to minimize the amount of antisera used with western blots.

PMID- 7513974
TI  - Detection of calcium binding proteins on polyacrylamide gels using time-resolved
      lanthanide luminescence photography.
AB  - Methods were developed for using the luminescent lanthanides Tb3+ and Eu3+ for
      the specific staining of calcium-binding proteins, as well as the nonspecific
      staining of proteins, on polyacrylamide gels. These methods involve equilibration
      of the gel after electrophoresis in solutions containing the appropriate
      lanthanide and a weak competitive chelating agent, such as N-(2
      hydroxyethyl)iminodiacetic acid or nitrilotriacetic acid. This staining has the
      potential for complete reversibility using stronger chelating agents such as EDTA
      or diethylenetriaminepentaacetic acid, to allow for recovery of the protein.
      Specific staining produces an intense luminescent signal from those metal-binding
      proteins which have been modified either chemically or via site-directed
      mutagenesis. Gels were photographed using a time-resolved fluorescence camera
      system.

PMID- 7513976
TI  - Ethidium bromide staining during denaturation with glyoxal for sensitive
      detection of RNA in agarose gel electrophoresis.

PMID- 7513977
TI  - Multisample analysis using an array of microreactors for an alternating-current
      field-enhanced latex immunoassay.
AB  - To develop a rapid and multisample analysis system for latex immunoassay with
      submicroliters of sample, an array of microreactors were fabricated using
      micromachining techniques including photolithography, anisotropic etching, and
      thin gold film deposition. The chamber volume for immunoreactions of a single
      well was 0.4 microL. An alternating-current (ac) field was used to enhance the
      rate of the latex agglutination reaction. By applying an ac field for 1 min,
      alpha-fetoprotein in several samples could be determined simultaneously. The
      detection limit in this system was approximately 10 pg/mL.

PMID- 7513978
TI  - Subdivision of the mitotic cycle into eleven stages, on the basis of the
      chromosomal changes observed in mouse duodenal crypt cells stained by the DNA
      specific Feulgen reaction.
AB  - The Feulgen reaction has been utilized to localize DNA in nuclei throughout the
      cycle of mouse duodenal crypt cells using Epon-embedded 1 micron thick sections.
      The observed changes indicate that the 12.3 h long mitotic cycle of these cells
      can be subdivided into eleven stages, seven of which take place during the
      interphase. Computer measurements of Feulgen-stained nuclei and previous
      radioautographic studies indicate that DNA synthesis begins during stage I and
      ends during stage IV. The staining pattern shows no distinctive feature in the
      nuclei of the 1.5 h long stage I. Thereafter, marked changes occur during the
      rest of the interphase--that is during the 6.3 h that precede karyokinesis and
      the 3.5 h that follow it. Thus, at stage II the background of the nuclei darkens;
      at stage III, there appear stained threads interpreted as densifying chromosomes
      and dots interpreted as chromomeres, both of which thicken from 0.2 to 0.4
      micron; at stage IV they further thicken to about 0.5 micron and at stage V, to
      about 0.7 micron. At this stage, which approximately corresponds to prophase, the
      intensely stained, discrete dots are localized within the less intensely stained
      sausage-shaped threads. As the breakup of the nuclear envelope introduces stage
      VI, whose early part corresponds to prometaphase, the intensely stained dots
      become close to one another within the threads and eventually fuse. The staining
      of the threads thus intensifies, and, by the late part of the stage that
      corresponds to metaphase, they have become the homogeneously dense metaphase
      chromosomes. At stage VII, the anaphase chromosomes reach each pole where they
      associate into a compact mass.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513979
TI  - [Interferons. Structure, functions and therapeutic applications of interferons].

PMID- 7513980
TI  - [Interferons. Treatment of malignant hemopathies with interferons].
AB  - Interferons (INF) are glycoproteins with protean antiviral, immunomodulator, and
      antiproliferative actions. In Haematology, IFN-alpha is the most widely used.
      Diffusion into the spleen, bone marrow and liver is good. Hairy cell leukemia is
      probably the malignant blood disorder which responds best to IFN. At some time
      during their treatment, nearly 90% of the patients require IFN. Treatment
      initiation is indicated when pancytopenia (polynuclear neutrophils below 1 x
      10(9)/L) develops or in case of a very voluminous spleen. IFN-alpha 2a, 2b and 2c
      are active (leukocyte IFN is used less often, as is IFN-beta; IFN-gamma is
      ineffective). The standard dose is 3 x 10(6) U, three times a week for 12 weeks.
      Smaller doses and maintenance treatment is sometimes proposed. Haematological
      remission occurs in almost all cases, if not a misdiagnosis must be considered
      (villous lymphocyte lymphoma). Relapse usually occurs at the end of treatment,
      but sensitivity to IFN is not altered and final survival is improved. Nearly 90%
      of the patients are alive at 4 years. Although IFN is active in chronic myeloid
      leukemia, research in this area continues. Clinical trials have reported
      haematologic relapse in 90% and complete cytogenetic response in 15 to 35% of the
      patients. The effect on Ph+ cells is not observed with classical chemotherapies.
      Initial dose is generally 5 x 10(6) U/m2/day. High doses are not always well
      tolerated, but cytogenetic response is only seen in patients in haematologic and
      cytopenic remission. IFN therapy improves survival over classical treatments
      (median 62 versus 39 months). Survival is better after good cytogenetic response
      or complete remission. Combined chemo-IFN therapy is currently under study in an
      attempt to improve cytogenetic response. In terms of the molecular biology
      however, residual disease is almost always present and relapse is
      frequent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513981
TI  - Correlation of clinical features and findings on cranial magnetic resonance
      imaging with urinary myelin basic protein-like material in patients with multiple
      sclerosis.
AB  - Immunoreactive material that appears to be a peptide encompassing all or a
      portion of residues 80 to 89 of myelin basic protein is present in normal
      unconcentrated urine and is increased in certain patients with multiple sclerosis
      (MS). Compared with normal controls, urines collected randomly from 158 MS
      patients or in a clinical research unit from 8 patients with MS had higher mean
      values of urinary MBP-like material (MBPLM). The level of MBPLM in urine showed
      no direct relationship to MBPLM in cerebrospinal fluid and did not correlate with
      clinical relapses of disease. In the other neurological disease control group (26
      patients), some patients with other inflammatory diseases, but not stroke or
      early phase Guillain-Barre syndrome, also showed elevations. Among the subtypes
      of MS, those with secondary chronic progressive disease had the highest values.
      Urinary MBPLM showed no definite correlation with or effect of treatment with
      glucocorticoids and immunosuppressants except that a lower level of urinary MBPLM
      showed a weak relationship with improvement following treatment with
      methylprednisolone/prednisone. In a serial study of 8 patients with unenhanced
      cranial magnetic resonance imaging and 20 patients with gadolinium-enhanced
      cranial magnetic resonance imaging, urinary MBPLM did not show a direct
      correlation with new or enhancing lesions. Urinary MBPLM does not parallel acute
      myelin damage but appears to reflect an ongoing process, possibly linked to
      attempted efforts at remyelination.

PMID- 7513982
TI  - Transgenic mouse brain histopathology resembles early Alzheimer's disease.
AB  - Transgenic mice expressing the 751-amino acid form of the human amyloid precursor
      protein develop extracellular beta-amyloid protein (A beta)-immunoreactive
      deposits that increase in frequency with age. Here we show that the appearance
      and histological profile of deposits in the transgenic mice closely resemble
      those of preamyloid deposits in the brains of young adults with Down's syndrome,
      who presumably have the pathology of early-stage Alzheimer's disease. Specific
      monoclonal antibodies reveal that material in the deposits has the free carboxyl
      terminus of A beta 1-42, and that the deposits contain material which, by
      immunohistochemical analysis, apparently originates from the human beta-amyloid
      precursor protein (beta PP) transgene. In rare cases, the transgenic mouse brains
      contain several different histopathological characteristics of Alzheimer lesions.
      These features include dense A beta immunoreactivity which co-localizes with
      gliosis and with Alz50-immunoreactive structures resembling swollen boutons of
      dystrophic neurites. These observations demonstrate that the murine brain is
      capable of reproducing several typical features of Alzheimer histopathology.

PMID- 7513983
TI  - Elevated serum levels of endothelial leukocyte adhesion molecules in Guillain
      Barre syndrome and chronic inflammatory demyelinating polyneuropathy.
AB  - We determined the serum concentrations of the soluble form of endothelial
      leukocyte adhesion molecule-1 (sELAM-1) in 25 patients with Guillain-Barre
      syndrome, 14 patients with chronic inflammatory demyelinating polyneuropathy, 15
      patients with amyotrophic lateral sclerosis, 15 patients with other
      polyneuropathies, 10 patients with acute stroke, and 12 healthy control subjects.
      The patients with Guillain-Barre syndrome in the acute stage had a higher sELAM-1
      serum level compared with the control subjects (p < 0.001). In 7 of the 9
      patients the elevated level returned to normal by 14 days after the onset of
      neurological symptoms. In addition, a significantly elevated serum level of sELAM
      1 was found in patients with chronic inflammatory demyelinating polyneuropathy (p
      < 0.01). These findings suggest a role for ELAM-1 in the inflammatory process of
      these disorders.

PMID- 7513984
TI  - CD44 expression in colorectal adenomas is an early event occurring prior to K-ras
      and p53 gene mutation.
AB  - Neoplastic progression of colorectal epithelial cells from benign adenomas to
      malignant carcinomas appears to result from a series of genetic alterations
      involving both oncogenes and tumor suppressor genes. This progression was
      recently found to be associated with expression of splice variant isoforms of
      CD44, a cell surface hyaluronate receptor implicated in carcinogenesis. In this
      study we examined the relationship of CD44 expression to somatic genetic events
      in the adenoma-carcinoma sequence: point mutation of K-ras in codons 12 and 13
      and overexpression of p53 protein as a marker of gene mutation. Among 22 small
      adenomas, CD44 was present in 9 (41%), of which only 1 contained a K-ras
      mutation. CD44 was absent in the other 2 small adenomas positive for K-ras
      mutation or p53 overexpression. In contrast to the early expression of CD44 in
      small adenomas, mutations of K-ras and p53 were detected preferentially in large
      adenomas and late-stage adenomas containing carcinoma. The frequent expression of
      CD44 prior to K-ras and p53 gene alterations in colorectal neoplasia suggests
      that activation of CD44 gene expression is related to earlier events in the
      adenoma-carcinoma sequence, possibly cell activation and proliferation following
      APC gene mutation or alteration of DNA methylation.

PMID- 7513985
TI  - Intradermal bleomycin injections into normal human skin. A histopathologic and
      immunopathologic study.
AB  - BACKGROUND: Intralesionally injected bleomycin is a useful agent for the
      treatment of recalcitrant warts. The mechanism of action in wart therapy has been
      thought to be due to DNA and antiviral effects. To further characterize the
      inflammatory response to intralesional bleomycin injections, we examined the
      clinical, histologic, and immunopathologic response to intradermal bleomycin
      injections in normal human skin. RESULTS: Four volunteers were each given four
      intradermal bleomycin injections (0.01 to 0.5 U/mL) into normal human skin to
      establish a dose response. These injections induced a localized time and dose
      dependent inflammatory reaction and persistent postinflammatory
      hyperpigmentation. Nine biopsy specimens from two volunteers were taken at
      different time points after intradermal bleomycin injections (0.1 to 1.0 U/mL)
      into normal human skin. Routine histologic study demonstrated dyskeratosis and
      necrosis of epidermal keratinocytes and eccrine epithelium associated with a
      prominent neutrophilic infiltrate, closely resembling histopathologic findings
      seen in neutrophilic eccrine hidradenitis. Expression of HLA-DR and intercellular
      adhesion molecule 1 was induced on keratinocytes; intercellular adhesion molecule
      1 was upregulated, and endothelial leukocyte adhesion molecule 1 was induced on
      superficial dermal blood vessels. CONCLUSIONS: These findings suggest that
      intradermal bleomycin injection is either directly or indirectly cytotoxic to
      keratinocytes and eccrine epithelium. Expression and upregulation of activation
      antigens and cell adhesion molecules suggest that a cellular immune system
      response and proinflammatory cytokine secretion occur after intralesional
      bleomycin injection into normal human skin. Histopathologic findings at some
      injection sites resemble neutrophilic eccrine hidradenitis.

PMID- 7513986
TI  - CD34 staining pattern distinguishes basal cell carcinoma from trichoepithelioma.
AB  - BACKGROUND AND DESIGN: Trichoepithelioma is a benign skin tumor with follicular
      differentiation, which sometimes is difficult to distinguish clinically and
      histologically from basal cell carcinoma. One of the most helpful differences is
      the histologic appearance of the stroma. CD34 is an antigen known to stain the
      spindle-shaped cells located around the middle portion of normal hair follicles.
      We have stained formalin-fixed, paraffin-embedded sections of 16
      trichoepitheliomas and 19 basal cell carcinomas for CD34 (anti-HPCA-1, Becton
      Dickinson, San Jose, Calif) to detect differences in the staining pattern and to
      facilitate discrimination of these two types of tumors. RESULTS: The spindle
      shaped cells surrounding the islands of trichoepithelioma cells were focally
      strongly positive for CD34. In all basal cell carcinomas, the spindle-shaped
      cells surrounding the nests of tumor cells were negative; in these areas only the
      blood vessels were positive with this antibody. CONCLUSIONS: CD34 staining
      pattern differentiates between trichoepithelioma and basal cell carcinoma. CD34
      stain may be helpful in distinguishing between these two tumors on small punch
      biopsies or in difficult diagnostic cases.

PMID- 7513987
TI  - CD34+ spindle-shaped cells selectively disappear from the skin lesion of
      scleroderma.
AB  - BACKGROUND AND DESIGN: The pathogenesis of scleroderma is still unknown.
      Recently, it has become possible to identify different subpopulations of dermal
      spindle-shaped cells using anti-CD34 and anti-factor XIIIa antibodies. To
      elucidate whether entire populations of dermal fibroblasts or only a
      subpopulation of cells are involved in the fibrosis of scleroderma, we compared
      the staining pattern of these antibodies and antiprocollagen antibody in paraffin
      embedded skin sections from the lesions of 27 patients with scleroderma and 15
      patients with other collagen diseases and from normal skin of 17 subjects.
      Cryostat sections from both involved and uninvolved skin of four patients with
      scleroderma were also stained with anti-CD34, anti-factor XIIIa, and anti-proline
      4-hydroxylase antibodies. RESULTS: CD34+ cells were few or absent in the lesions
      of scleroderma, while a number of CD34+ cells were found in the lesions of other
      collagen diseases and in normal skin. In contrast, large numbers of factor XIIIa
      and procollagen-positive cells were noted in the lesions of scleroderma. Even in
      the study in which cryostat sections were used, CD34+ cells were totally absent
      from the lesions of scleroderma, while there were numerous proline-4-hydroxylase
      positive cells. Furthermore, although detectable in the clinically uninvolved
      skin of these patients, CD34+ cells were less frequent and more slender than
      those in normal skin. CONCLUSION: Immunohistologic staining with anti-CD34 and
      other antibodies to dermal spindle-shaped cells demonstrated a selective
      disappearance of CD34+ spindle-shaped cells from the lesions of scleroderma. It
      suggests that CD34+ cells might be important target cells in the autoreactive
      phenomenon in scleroderma.

PMID- 7513988
TI  - CD34, stem cells, and the skin.

PMID- 7513989
TI  - Clinical experience with Montgomery salivary bypass stents in the esophagus.
AB  - Thirty-seven patients with locally advanced malignancy (18, esophageal
      obstruction; 19, esophageal fistula formation) underwent attempted placement of a
      Montgomery salivary stent in the esophagus. This was unsuccessful in 3; in 2,
      because of inability to dilate, and, in 1, because of perforation. After dilation
      of the esophagus, there was no detectable underlying stricture in 11 patients;
      none of these patients experienced stent migration. Overall, there was 100%
      success in obliterating the fistulous tract, an 8.1% incidence of retrograde
      migration, no incidence of prograde migration, and no incidence of stent
      obstruction after discharge. Of the 34 patients with successfully placed stents,
      27 were discharged from hospital, and were able to eat and drink without the need
      for intravenous supplementation or gastrostomy tube feedings. The survival in
      patients presenting with obstruction ranged from 1 to 13 months (mean, 8.0
      months); the survival in patients presenting with a fistula ranged from 2 to 7
      months (mean, 5.3 months).

PMID- 7513990
TI  - Tracheal stenting for malignant tracheoesophageal fistula.
AB  - Palliative intubation of the esophagus for a malignant tracheoesophageal fistula
      is often complicated by difficulty in obtaining a tight seal. We have overcome
      the problem in three instances by placing a bifurcated, foam-cuffed stent in the
      trachea.

PMID- 7513991
TI  - Alternative splicing of CD44 pre-mRNA in human colorectal tumors.
AB  - Expression of the CD44 molecule has been linked to tumor growth and metastases in
      both human and rodent cancers. Alternatively spliced variants expressed in rat
      and mouse tumors have been shown to confer metastatic potential to non-metastatic
      carcinoma cell lines, and human homologues of rat variant mRNA sequences are
      expressed in human tumors. In the present study matched sets of RNA from
      adenocarcinomas of the colon and distant normal mucosa were assayed for CD44
      expression by quantitative RT-PCR. Retrospective analysis revealed that colonic
      tumor cells had both quantitative and qualitative differences in CD44 expression
      when compared to normal mucosa. These were: 1) an increase in levels of CD44
      transcripts, 2) an increase in levels of alternatively spliced transcripts, 3)
      the presence of larger alternatively spliced transcripts with inserts > 400 bases
      and 4) the primary alternatively spliced CD44 isoform in colonic adenocarcinomas
      in all cases is CD44R. Interestingly, two patterns of CD44 isoform expression
      termed "variant dominant" or "balanced" patterns of expression, based on the
      ratio of variant to standard CD44 transcripts (R+V's/H), could be differentiated.
      An unfavorable prognosis was suggested for tumors expressing increased levels of
      CD44 variant exons previously associated with tumor metastasis. Specifically,
      patients with tumors expressing the "variant dominant" pattern of expression
      irregardless of Dukes classification and Dukes C and D staged tumors of both
      patterns exhibited a poorer prognosis.

PMID- 7513992
TI  - Chiral discrimination of enantiomeric 2'-deoxythymidine 5'-triphosphate by HIV-1
      reverse transcriptase and eukaryotic DNA polymerases.
AB  - Inhibitory effects of 2'-deoxy-L-thymidine 5'-triphosphate (L-dTTP), the
      enantiomer of the natural substrate D-dTTP, on the activity of mammalian DNA
      polymerases alpha, beta and gamma, Escherichia coli DNA polymerase I and human
      immunodeficiency virus 1 (HIV-1) reverse transcriptase were examined. When
      poly(rA)n-oligo(dT)12-18 was used as the template-primer, L-dTTP showed
      remarkable inhibitory effect on HIV-1 reverse transcriptase in competitive
      fashion with respect to the substrate dTTP. In contrast, L-dTTP did not inhibit
      DNA polymerases alpha and was slightly inhibitory to DNA polymerase beta. These
      results suggest that the nuclear DNA polymerases alpha and beta showed high
      specificity for the substrate with the natural configuration of the sugar moiety,
      D-dTTP, exhibiting little or no ability to recognize L-dTTP, whereas HIV-1
      reverse transcriptase essentially lacked the ability to differentiate the D- and
      L-sugar moieties.

PMID- 7513993
TI  - Semi-artificial hydroxylating enzymes created by flavins binding to cytochrome
      P450 2B4 and by bleomycin binding to NADPH-cytochrome P450 reductase.
AB  - To create a semi-artificial monomolecular oxygenase system, FAD or FMN were
      covalently bound to cytochrome P450 2B4 as electron donor centers and bleomycin
      to NADPH-cytochrome P450 reductase as a generator of active oxygen species. The
      most catalytically active was the conjugate of cytochrome P450 with FMN, able to
      initiate the reactions of dimethylaniline and aminopyrine demethylation along
      with the reaction of aniline p-hydroxylation. The conjugate of cytochrome P450
      with FAD oxidized these substrates at a much slower rate. The bleomycin-reductase
      complex was capable of demethylating dimethylaniline and aminopyrine but failed
      to oxidize aniline.

PMID- 7513994
TI  - Selective targeting of nitric oxide synthase inhibitors to system y+ in activated
      macrophages.
AB  - Amino acid transport systems mediating uptake of nitric oxide (NO) synthase
      inhibitors were characterized in the murine macrophage cell line J774. Treatment
      of J774 cells with bacterial endotoxin (LPS, 1 microgram ml-1, 24 h) selectively
      increased the transport capacity for NG-monomethyl-L-[14C]arginine (L-NMMA),
      whereas transport of NG-nitro-L-[3H]arginine (L-NNA) was unaffected. Inhibition
      studies established that the cationic transport system y+ mediates uptake of L
      arginine, L-NMMA and NG-iminoethyl-L-ornithine (L-NIO). A neutral transporter,
      with low substrate specificity and insensitive to LPS, mediates uptake of L
      citrulline, L-NNA and its methyl ester L-NAME. We conclude that enhanced
      expression of the y+ transporter in LPS-stimulated macrophages may facilitate the
      targeting of selective inhibitors of inducible NO synthase to activated cells
      generating NO in endotoxin shock.

PMID- 7513995
TI  - Promoter analysis of human inducible nitric oxide synthase gene associated with
      cardiovascular homeostasis.
AB  - We previously showed that interferon (IFN)-gamma inhibited the proliferation of
      rat vascular smooth muscle cells (VSMC) by generation of nitric oxide (NO)
      through the induction of an NO synthase (NOS) and cloned the rat inducible NOS
      cDNA in VSMC (VSM-NOS). To study the regulation of human inducible NOS (hiNOS)
      transcription in VSMC, we now cloned and sequenced a 2.9-kb fragment for the
      hiNOS gene containing a putative promoter, exon 1 and exon 2. The 5'-flanking
      region contains several consensus sequences for the binding of transcription
      factors involved in the inducibility of other genes by cytokines. These include
      IFN-gamma responsive element and NF-IL6 and NF-kappa B binding consensus
      sequences. Interestingly, hiNOS gene contains a shear-stress responsive element
      (GAGACC) which was also found to exist in human endothelial-type NOS but not in
      murine inducible NOS.

PMID- 7513998
TI  - Liver transplantation for Budd-Chiari syndrome--palliation or cure?
AB  - This report documents two cases of Budd-Chiari syndrome (BCS) with essential
      thrombocytosis and antithrombin (AT) III deficiency as underlying etiological
      factors. Orthotopic liver transplantation was successfully performed in both
      patients but with different therapeutic intention. In the patient with essential
      thrombocytosis, hepatic transplantation only relieved the symptoms of the
      predisposing thrombogenic condition; it did not cure the underlying disorder.
      Prophylactic long-term anticoagulation, as well as adjuvant therapy for the
      causative disease, remained necessary. On the other hand, in the patient with AT
      III deficiency, liver transplantation was curative, resulting in complete
      reconstitution of serum AT III activity with resolution of the hypercoagulable
      state postoperatively. Thus, depending on the underlying etiology, liver
      transplantation for BCS can be considered as palliative, necessitating long-term
      adjuvant therapy, or as curative, with correction of a metabolic defect.

PMID- 7513996
TI  - Molecular cloning and expression of a novel human gene that is highly homologous
      to human FK506-binding protein 12kDa (hFKBP-12) and characterization of two
      alternatively spliced transcripts.
AB  - We isolated a novel gene encoding a protein highly homologous to human FK506
      binding protein 12kDa (hFKBP-12) from a human fetal brain cDNA library and
      determined the full-length cDNA sequence. The cDNA clone contained the open
      reading frame of 324 nucleotides encoding 108 amino acid and revealed 76%
      identity in DNA sequence and 88% identity in predicted amino acid sequence with
      hFKBP-12. The DNA and amino-acid sequence of this gene, designated OTK4, also had
      homology with other FKBPs in species ranging from humans to prokaryotes.
      Recombinant protein, produced in E.coli transformed by a pGEX2T expression vector
      containing the OTK4 cDNA and purified, showed peptidyl-prolyl cis-trans isomerase
      activity like other FKBP proteins. An alternatively spliced form of the
      transcript found in the cDNA library contained a 45-bp insertion which included a
      stop codon. Although the biological function of the truncated version of OTK4 is
      unknown, both transcripts were ubiquitously expressed in human tissues examined
      by the reverse-transcriptase PCR (RT-PCR) method.

PMID- 7513997
TI  - Serum amylase determinations in pediatric patients presenting to the ED with
      acute abdominal pain or trauma.
AB  - The objective of this study was to evaluate the overall impact of serum amylase
      determinations in the initial management of patients presenting to the pediatric
      emergency department (ED) with the acute onset of abdominal pain or trauma. All
      cases of patients younger than 18 years of age who presented to the pediatric ED
      for whom a serum amylase value was determined during an 18-month period were
      reviewed. Data were collected retrospectively, including serum amylase
      concentration, age, gender, presenting complaint, discharge/admission status,
      diagnosis, and discharge plans or inpatient management to evaluate the impact of
      serum amylase determinations. Seven hundred twenty-three cases were reviewed
      during the study period. Six hundred fifty-six patients met study criteria, with
      385 serum amylase determinations performed for the evaluation of acute abdominal
      pain and 271 for acute trauma. Sixty-seven serum amylase determinations were also
      sent for other reasons. Overall, 12 of 656 study patients had elevated amylase
      levels (1.8%) during the study period (range, 130 to 2318 U/L). Eight of 271
      amylase levels sent to the laboratory for trauma (3.0%), and 4 of 385 sent for
      abdominal pain (1.0%) were elevated. Overall, serum amylase concentration had no
      influence on whether or not the patient was admitted to the hospital. Of the 12
      patients with elevated amylase levels sent for abdominal pain or trauma, only 2
      had their clinical management affected by the serum amylase concentration. In
      both cases, the patient presented with subacute abdominal pain related to
      significant abdominal trauma that had occurred 2 to 3 weeks earlier. Both
      patients showed evidence of pancreatic insult with diagnostic imaging
      studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7513999
TI  - Mucosal recipient-type mononuclear repopulation and low-grade chronic rejection
      occur simultaneously in indefinitely surviving recipients of small bowel
      allografts.
AB  - Lewis rat recipients of long-term, surviving, orthotopic Brown-Norway rat
      intestinal allografts, initially treated with cyclosporin A (CyA) or FK 506, were
      evaluated for their functional capacity and morphology over 1 year after the
      immunosuppressive therapy had been discontinued. Functional parameters such as
      nitrogen and fat balances, maltose absorption, blood chemistry, hematologic
      studies, and the weight gained by the allografted animals did not differ from
      those of syngeneically grafted or age-matched normal animals. Immunohistochemical
      studies showed that the lamina propria of the allografts was repopulated with
      recipient MHC class II+ mononuclear cells and that a normal distribution of T
      helper, T suppressor/killer, and IgA+ plasma cells had occurred. However, fibrous
      replacement of the mesenteric lymph nodes and Peyer's patches were detected in
      all, and an inflammatory obliterative arteriolopathy developed in the mesenteric
      vasculature of half of the allografted animals. No such findings were observed in
      recipients of syngeneic grafts. These results demonstrate that the limited use of
      potent immunosuppressive agents immediately after transplantation averts
      rejection and is followed by recipient-type mucosal lymphocytic repopulation.
      Simultaneously, a clinically not recognizable chronic rejection evolves. This
      suggests that the timely diagnosis of chronic rejection may not be possible with
      the use of standard tests of gut function and random mucosal biopsies alone.

PMID- 7514002
TI  - Expression of the Alcaligenes eutrophus phbA gene in Escherichia coli using a
      positive selection vector based on phage Lambda lysis genes.
AB  - A new positive selection vector, pGS23, based on the Lambda lysis cassette has
      been designed for efficient expression of homologous and heterologous genes in
      Escherichia coli. The plasmid permits controlled expression of a gene of interest
      under transcriptional control of the lac promoter with translation initiation of
      coding sequences directed by the phage T7 gene 10 ribosome binding site. The
      application of the vector system was tested for high level expression of the
      heterologous phbA gene of Alcaligenes eutrophus in E. coli.

PMID- 7514003
TI  - Improved separation of glyoxalated viroid RNAs and other small nucleic acids in
      polyacrylamide gels containing urea.

PMID- 7514004
TI  - Isolation and cloning of DNA amplification products from silver-stained
      polyacrylamide gels.

PMID- 7514005
TI  - Matrix-assisted laser desorption mass spectrometric analysis of a pegylated
      recombinant protein.
AB  - Matrix-assisted laser desorption ionization mass spectrometry (MALDI) has been
      investigated as a technique for the characterization of recombinant stem cell
      factor that had been covalently modified with polyethylene glycol (PEG) chains.
      The attachment of PEG chains produces a heterogeneous mixture of protein species
      that differ by 6000 Da. These differences in molecular weight could be readily
      determined by MALDI. The potential of MALDI as a general strategy for
      characterizing PEG-modified proteins is discussed.

PMID- 7514006
TI  - A coupled one-step reverse transcription PCR procedure for generation of full
      length open reading frames.
AB  - A one-step (all reactants added simultaneously) reverse transcription and
      polymerase chain reaction (RT-PCR) procedure for amplification of full-length
      open reading frames (ORFs) of relatively rare transcripts was developed. It was
      applied for cloning rat luteinizing hormone/chorionic gonadotropin receptor cDNA
      isoforms larger than two kb. In the procedure developed, manual work is
      minimized, thus large numbers of samples can be handled, since after denaturation
      of template RNA and the primers and addition of other reagents, no further manual
      steps are needed. No inhibitory effect of avian myeloblastosis virus (AMV)
      reverse transcriptase (RT) on Thermus aquaticus (Taq) DNA Polymerase was found.
      This was because, under the conditions described, Taq DNA Polymerase effectively
      amplified picogram amounts of plasmid DNA or template reverse transcribed from
      nanograms of total ovarian RNA in the presence of AMV-RT. Even a large excess of
      AMV-RT did not inhibit Taq DNA Polymerase. Thus, our coupled one-step RT-PCR
      procedure amplifies fast and reproducibly full-length ORFs from nanogram amounts
      of total RNA.

PMID- 7514007
TI  - Storage phosphor imaging technique improves the accuracy of RNA quantitation
      using 32P-labeled cDNA probes.
AB  - The use of the storage phosphor imaging technique to quantitate radioactivity on
      blots generated by hybridization with 32P-cDNA probes was evaluated and compared
      with screen-enhanced x-ray film autoradiography. Quantitation of RNA dot blots
      hybridized with a 28S ribosomal RNA-specific cDNA probe showed that storage
      phosphor imaging was more sensitive than screen-enhanced x-ray film
      autoradiography in identifying low amounts of total RNA (1-10 micrograms).
      Evaluation of Northern blots containing 30 micrograms of total RNA from human
      skin biopsies hybridized with a cDNA probe for the human acidic ribosomal
      phosphoprotein, PO, showed that both techniques detected random biological
      variability of this housekeeping gene in a similar manner. The two techniques
      exhibited a strong linear correlation in their ability to quantitate mRNA levels
      of a retinoic acid-inducible gene (RIS-1). This correlation was stronger at
      levels corresponding to 1-fold to 30-fold increases of signal and decreased
      beyond this range because of the insensitivity of the x-ray film. In conclusion,
      storage phosphor imaging is more accurate than screen-enhanced x-ray film
      autoradiography in identifying different RNA amounts (higher sensitivity) and in
      detecting increasing RNA signals at high levels of radioactivity (higher dynamic
      range).

PMID- 7514000
TI  - Control of receptor sensitivity at the mRNA level.
AB  - Neurons are able to adjust the sensitivity of receptor-mediated processes
      according to the level of receptor activation. Extrapolating from our knowledge
      of other cellular proteins, regulation of receptor mRNA availability would
      provide a highly economical means of achieving this objective. Epidermal growth
      factor is able to induce long-lasting increases in its receptor binding by
      increasing receptor mRNA levels, and similar effects have been shown for other
      growth factors. Studies on G-protein-coupled receptors, in particular using
      adrenoceptor clones transfected into cultured cell lines, have shown that changes
      in receptor number are generally associated with an alteration in receptor mRNA
      content. At the neuromuscular junction, dramatic increases in nicotinic
      acetylcholine receptor number are achieved by activating receptor subunit gene
      transcription. Less information is available concerning the regulation of ligand
      gated ion channels in the brain. Overall, the evidence suggests that receptor
      mRNA levels are frequently controlled by the degree of receptor stimulation.
      Receptor mRNA levels are therefore likely to be one of the most important control
      points for both homologous and heterologous regulation of receptor sensitivity.

PMID- 7514008
TI  - Major human epididymis-specific gene product, HE3, is the first representative of
      a novel gene family.
AB  - Differential screening of a human epididymal cDNA library led to the isolation
      and characterization of a major epididymis-specific cDNA clone family, referred
      to as HE3. More detailed sequence and PCR analysis identified two different but
      homologous gene transcripts, HE3 alpha and HE3 beta. The former represents an
      mRNA of ca. 1 kb, encoding a putative small secretory polypeptide of 14903 MW.
      The HE3 beta transcript was only found as incomplete 3' fragments. Analysis of
      human genomic DNA by Southern blotting suggested the presence in the human genome
      of at least three independent HE3-related genes. Isolation of genomic clones for
      the HE3 alpha gene showed this to contain a single intron of 1.4 kb in the 5'
      noncoding region. Although genomic clones corresponding to HE3 beta could not be
      found, a third highly homologous gene, HE3 gamma, was identified as a potential
      pseudogene. Neither nucleotide nor encoded amino acid sequences of the HE3 gene
      family are related to any other known sequence in the central databases, and thus
      represents a novel human gene family, with at least three nonallelic members.
      Northern hybridization analysis showed that HE3 gene products are specifically
      expressed in the human epididymis, and not in any other tissue examined.
      Furthermore, except for the pig, no other nonprimate species has been identified
      to express homologous sequences in the epididymis. RNase protection assays showed
      that both the HE3 alpha and HE3 beta, but not the HE3 gamma genes, are expressed
      in the human epididymis.

PMID- 7514009
TI  - Manganese superoxide dismutase and heat shock protein 70 are not necessary for
      suppression of apoptosis in human peripheral blood neutrophils.
AB  - We have previously shown that granulocyte (G-CSF) and granulocyte/macrophage (GM
      CSF) colony-stimulating factors present in human bronchial epithelial cell
      conditioned medium (HBEC-CM) suppress apoptosis in neutrophils. In this study, we
      demonstrate that HBEC-CM also induces increased expression of manganese
      superoxide dismutase (MnSOD) and heat shock protein 70 (HSP70) in neutrophils.
      However, treatment of neutrophils with recombinant GM-CSF and G-CSF, which
      suppressed apoptosis to equivalent degrees, did not induce MnSOD or HSP 70. Thus,
      we conclude that induction of stress proteins is associated with, but not
      necessary for, suppression of apoptosis.

PMID- 7514010
TI  - Carbonic anhydrase II expression in rat type II pneumocytes.
AB  - Pulmonary carbonic anhydrase (CA) activity plays important roles in carbon
      dioxide exchange, fluid secretion, and pH regulation. This study reports the use
      of molecular and immunologic techniques to characterize expression of the high
      activity cytosolic isoenzyme CA II in rat lung tissue. Northern blot analysis of
      RNA isolated from various rat tissues revealed that the lung is a site of
      abundant tissue-specific CA II gene expression. The cell type primarily
      responsible for CA II expression in the lung was identified by
      immunohistochemistry as the alveolar type II pneumocyte. RNA blot and immunoblot
      analyses of isolated rat type II cells in culture confirmed CA II expression by
      this cell type. Little immunoreactive CA I and no CA IV was detected in these
      cells. Inhibition studies confirmed that the majority of CA activity in isolated
      type II cells is attributable to CA II. CA II expression was found to continue in
      these cells beyond 72 h in culture, a timeframe during which these cells had
      dedifferentiated. The ontologic pattern of CA II expression in the lung was found
      by RNA blot analysis to be disparate from that of the surfactant-associated
      proteins. These observations suggest roles for CA II in alveolar pneumocytes
      independent of (or in addition to) participation in surfactant biology. Such
      roles may include the regulation of fluid secretion or facilitation of carbon
      dioxide elimination.

PMID- 7514001
TI  - Receptor-receptor interactions as an integrative mechanism in nerve cells.
AB  - Several lines of evidence indicate that interactions among transmission lines can
      take place at the level of the cell membrane via interactions among
      macromolecules, integral or associated to the cell membrane, involved in signal
      recognition and transduction. The present view will focus on this last subject,
      i.e., on the interactions between receptors for chemical signals at the level of
      the neuronal membrane (receptor-receptor interaction). By receptor-receptor
      interaction we mean that a neurotransmitter or modulator, by binding to its
      receptor, modifies the characteristics of the receptor for another transmitter or
      modulator. Four types of interactions among transmission lines may be considered,
      but mainly intramembrane receptor-receptor interactions have been dealt with in
      this article, exemplified by the heteroregulation of D2 receptors via
      neuropeptide receptors and A2 receptors. The role of receptor-receptor
      interactions in the integration of signals is discussed, especially in terms of
      filtration of incoming signals, of integration of coincident signals, and of
      neuronal plasticity.

PMID- 7514012
TI  - Platelet-derived growth factor induces phosphatidylinositol 3-kinase release from
      the middle T-pp60c-src complex and association with the platelet-derived growth
      factor receptor.
AB  - Both platelet-derived growth factor (PDGF) and epidermal growth factor (EGF)
      induce mitogenesis in normal rat kidney (NRK) fibroblasts transformed by the
      polyoma virus middle T (pmt) oncogene. In unstimulated pmt-NRK cells
      phosphatidylinositol 3-kinase forms a complex with the middle T protein and pp60c
      src. PDGF treatment causes a release of phosphatidylinositol 3-kinase activity
      from the complex and a simultaneous increase in activity associated with the PDGF
      receptor. In contrast after treatment with EGF the majority of
      phosphatidylinositol 3-kinase activity remains associated with the middle T-pp60c
      src complex. Proliferation of NRK fibroblasts transformed by the v-src oncogene
      is already maximal, and no further stimulation is observed with either PDGF or
      EGF. Neither growth factor induces dissociation of the complex between
      phosphatidylinositol 3-kinase and pp60v-src. These observations suggest that the
      complex between phosphatidylinositol 3-kinase, the middle T protein and pp60c-src
      is dissociable, and that phosphatidylinositol 3-kinase plays different roles in
      mitogenic signal transduction by the PDGF and EGF receptors.

PMID- 7514011
TI  - Basic FGF and IGF-I promote differentiation of human SH-SY5Y neuroblastoma cells
      in culture.
AB  - Phorbolester-triggered differentiation of SH-SY5Y neuroblastoma cells requires
      serum and a prolonged activation of protein kinase C (PKC). Under serum-free
      conditions development of a mature phenotype requires phorbolester in combination
      with a member of either the insulin-like growth factor (IGF) or the platelet
      derived growth factor family. Here we report that basic and acidic fibroblast
      growth factor (FGF) and epidermal growth factor, but not nerve growth factor,
      synergistically potentiate phorbolester-induced differentiation. Alone these
      factors induced a mitogenic response which varied in magnitude, with basic FGF
      and IGF-I being the two most potent mitogens. However, a combination of basic FGF
      and IGF-I induced differentiation as judged by morphology and the increase in
      growth associated protein (GAP-43) and neuropeptide tyrosine mRNA levels. In
      contrast to the phenotype obtained in the presence of phorbolester, bFGF and IGF
      I-treated SH-SY5Y cells retained their capacity to proliferate. Finally, in these
      cells, the phosphorylation of the endogenous PKC substrate, myristoylated alanine
      rich C-kinase substrate (MARCKS), was slightly increased during several days,
      suggesting an involvement of PKC in the bFGF and IGF-I-induced differentiation.

PMID- 7514013
TI  - Phylogenetic study of ten new HTLV-I strains from the Americas.

PMID- 7514014
TI  - Attempted prophylaxis of human immunodeficiency virus type 1 infection in
      chimpanzees with a nonnucleoside reverse transcriptase inhibitor.

PMID- 7514015
TI  - An anti-gp41 human monoclonal antibody that enhances HIV-1 infection in the
      absence of complement.
AB  - B lymphocytes from tonsillar tissue of an asymptomatic HIV-1-seropositive subject
      were transformed with Epstein-Barr virus (EBV) and tested for the production of
      HIV-1-specific antibodies by ELISA, using purified HIV-1SF2.2F11, a monoclonal
      antibody derived from a transformed line, is of the IgG1 subclass and recognizes
      an epitope in the conserved region of the envelope transmembrane glycoprotein
      gp41, which is expressed on the surface of HIV-infected T cells. The antibody
      does not mediate the lysis of infected T cells in antibody-dependent cellular
      cytotoxicity (ADCC) assays and does not neutralize the infectivity of HIV-1SF2 or
      the homologous isolate HIV-1TT2.2F11 appears to be the first anti-gp41 human
      monoclonal antibody that enhances the infectivity of an HIV-1 strain (i.e.,
      SF128A) in the absence of complement.

PMID- 7514016
TI  - Characterization of HIV-1 strains isolated from patients treated with TIBO
      R82913.
AB  - The drug sensitivities of human immunodeficiency virus type 1 (HIV-1) isolates
      from a group of four untreated and seven TIBO R82913-treated patients were
      determined in a reverse transcriptase (RT) assay. Five of the treated patients
      harbored HIV-1 isolates with R82913 sensitivity comparable to that of the
      isolates of untreated patients, ranging from almost 2-fold higher sensitivity to
      13-fold lower sensitivity than that of recombinant p66 RT. From one of the seven
      treated patients, an HIV-1 strain with a 20-fold reduced sensitivity to R82913
      could be isolated; and from another patient, a strain with 100-fold reduced
      sensitivity (resistance) was isolated. The drug-resistant strain in this patient
      emerged after 3 weeks of treatment and was due to the Y188L mutation in its RT.
      On passaging the virus in cord blood lymphocytes, but not in CEM cells, the
      resistant virus was lost in favor of a different HIV-1 strain harboring the wild
      type Y188 with a sensitivity to R82913 comparable to that of wild-type p66 RT. In
      several HIV-1 isolates (from treated and untreated patients), some HIV-2- and
      CIVgab-specific amino acids were found. One of these substitutions, that is,
      I/V179D (from an untreated patient), conferred a sevenfold reduced RT sensitivity
      to R82913.

PMID- 7514017
TI  - Elemental microanalysis of fibroblasts by a scanning proton microprobe and
      application to Menkes' disease.
AB  - A scanning proton microprobe has been used for the elemental microanalysis of
      individual fibroblast cells. Both normal fibroblasts and fibroblasts cultured
      from patients with Menkes' disease, an X-linked genetic disorder known to be
      associated with defective copper metabolism, were examined by the probe. The
      cells were cultured on a thin ultra-clean nylon foil and retained on that surface
      for analysis. The focused high-energy proton beam was used to irradiate selected
      individual cells and elemental information was derived from X-ray and
      backscattered proton data. The sensitivity of the scanning proton microprobe to
      trace concentrations of heavy elements has allowed this elemental information to
      be used to identify individual cells as being either normal or a Menkes' mutant.
      The cell identification was based on the application of discriminate analysis to
      a data set formed from the ratios of copper to each of the macroelements present
      in the cell. This method of cell identification offers the promise of rapid
      diagnosis of Menkes' disease.

PMID- 7514018
TI  - The effect of aluminum chloride on some steps of heme biosynthesis in rats after
      oral exposure.
AB  - Certain disturbances in heme biosynthesis induced by aluminum chloride were
      examined. The experiment was performed on female rats that received AlCl3 orally
      at the dose 100 mg Al/kg daily for 21 d. The effects of aluminum on the activity
      of delta-aminolevulinic acid synthetase (ALA-S), dehydratase (ALA-D), and heme
      oxygenase (O.H.) were observed on 3, 7, 14, and 21 d in liver and kidneys of
      rats. Also the activity of ALA-D in blood and the concentration of delta
      aminolevulinic acid (ALA-U) in urine were observed. Orally administered aluminum
      caused increase in the activity of ALA-D in the liver and blood, and parallel
      decrease of ALA-U in urine (r = -0.85) of rats. Aluminum chloride also induced an
      increase of ALA-S and O.H. in the liver but not in the kidneys. The changes of
      the enzymes activity participating in heme biosynthesis after administration of
      aluminum may be correlated with anemia and iron metabolism in rats.

PMID- 7514019
TI  - An XRF study of trace elements accumulation in kidneys of tumor-bearing mice
      after treatment with cis-DDP with and without selenite and selenocistamine.
AB  - The effect of cis-DDP treatment with and without selenite and selenocistamine was
      studied on kidneys of tumor-bearing mice. The amounts of cis-DDP, selenite, and
      selenocistamine injected were chosen so as to be compatible with the treatment of
      humans. The animals were sacrificed at 7, 14, and 28 d after treatment. The
      kidneys were removed and subjected to trace element analysis by a novel X-ray
      fluorescence (XRF) method and for pathological assessment. The results show that
      following treatment with cis-DDP, K, Fe, Cu, and Zn reach a maximum level after 7
      d; K, Fe, and Cu levels were significantly reduced by the addition of selenite.
      The level of Zn was reduced only in groups treated with selenite whereas that of
      K and Cu was reduced also in groups treated with selenocistamine with and without
      cis-DDP. The greatest increase in Pt and Se levels was reached 1 wk after
      injection with cis-DDP, with and without selenocompounds, and in the case of Pt
      was partly reduced by addition of selenite. Se returned to control values 2 wk
      after injection, although Pt was still high in all groups 2 and 4 wk after
      injection. The results corroborate the findings of our previous studies. The
      effect of selenocistamine in cis-DDP treated mice was partly insufficient. The
      pathological examination of the kidneys did not show any differences in the
      effect of various additives during the study.

PMID- 7514020
TI  - Trace elements nutritional status. Use of hair as a diagnostic tool.
AB  - In this study, hair levels of Cu and Zn were determined in healthy male and
      female individuals (n = 192) ages 3.6-14.5 yr and the correlations with Cu and Zn
      daily intakes were examined. Determinations of Cu and Zn concentrations were
      performed by way of atomic absorption spectrometry and X-ray fluorescence.
      Nutritional data were collected with the aid of an individual questionnaire.
      Statistical analysis revealed no effect of age and sex either on Cu
      concentrations in hair or on Cu daily intakes. Zn concentrations were
      significantly higher in hair of both pubescent males and females compared with
      prepubescent individuals. There was no influence of age on Zn daily intake in
      males, however, whereas pubescent girls had a lower intake than males.
      Correlation coefficients between Cu concentrations in hair and daily nutritional
      intakes calculated for males and females were r = 0.1694 and r = 0.1677,
      respectively; those for Zn were r = -0.2223 (p < 0.05) in males and r = -0.2787
      (p < 0.01) in females. These data confirm that the analysis of Zn in hair
      represents an addition to conventional materials in the assessment of the
      nutritional status of groups of individuals.

PMID- 7514022
TI  - Measurement of the elemental composition of nasal-pharynx cancerous tissue with
      PIXE.
AB  - Twenty elements in two samples of nasal-pharynx cancerous tissue (NPCT) have been
      measured with PIXE. The results show that the element concentrations of calcium
      and zinc are very high, up to several thousand micrograms/g. Compared with
      results from other types of cancer patients, trace element concentrations in NPCT
      seem to be in a special status.

PMID- 7514021
TI  - Pharmacokinetics and pharmacodynamics in copper deficiency. I. Antiinflammatory
      activity of aspirin.
AB  - The effect of nutritional copper (Cu) deficiency on the antiinflammatory activity
      and pharmacokinetics of aspirin (ASA) was investigated in rats. Male, weanling
      Sprague-Dawley rats were fed either a Cu-deficient (CuD) or Cu-sufficient (CuS)
      diet for 49-50 d. The antiinflammatory activity of ASA was studied using the
      carrageenan-induced paw edema (CPE) test. ANOVA analyses of edema volumes at 2,
      3, 4, 5, and 21 h postcarrageenan indicated significant differences between
      groups. The percent inhibition of edema due to ASA treatment in CuS was lower
      than that in CuD rats at 5 h, AUC5h, and AUC21h. ASA was found to be
      significantly more effective in inhibiting the CPE in CuD rats when compared to
      the CuS rats. Thus, we hypothesized that the increase in ASA's antiinflammatory
      activity in CuD rats was a result of a decrement in its elimination during
      nutritional Cu deficiency. The elimination of ASA in CuD and CuS rats was studied
      using an iv dose of 200 mg/kg. Concentrations of ASA and salicylic acid (SA) were
      determined in blood; whereas the concentrations of SA, salicylic phenol
      glucuronide (SPG), and salicyluric acid (SUA) were determined in urine by HPLC.
      The results of the pharmacokinetic analyses from blood and urinary data indicated
      no significant differences in the disposition of ASA between CuD and CuS rats.
      For instance, the total body clearance for ASA (mean +/- SD, mL/min/kg) was 37.9
      +/- 9.4 and 38.5 +/- 13.9 (p > 0.05); and the volume of distribution (Vd) for ASA
      (mean +/- SD, mL/kg) was 385.5 +/- 110.3 and 397.1.1 +/- 137.9 (p > 0.05) for CuD
      and CuS groups, respectively. Thus, contrary to our hypothesis, the enhanced
      antiinflammatory activity of ASA in CuD rats does not appear to be mediated via a
      decrement in the elimination of the drug. In addition, plasma ASA-esterase
      activity was found to be independent of Cu nutritional status.

PMID- 7514023
TI  - Protein synthesis is not required for the inhibitory effect of selenite on cell
      colony formation and RNA synthesis.
AB  - Selenite has been shown to undergo intracellular metabolism that results in its
      conversion to other low molecular weight Se-containing species and also to its
      incorporation into a selenocysteine residue in selenoprotein. In order to
      investigate whether the incorporation into protein is required for the cytotoxic
      effects of selenite, we have examined whether inhibition of protein synthesis
      prevents the inhibitory effect of selenite on the ability of cells to form
      colonies or to synthesize RNA. We have found that treatment of HeLa cells with
      cycloheximide inhibited protein synthesis by > 90% but had no effect on the
      inhibitory effect of selenite on cell colony formation or RNA synthesis. Since
      protein synthesis is not necessary for these cytotoxic effects of selenite they
      are unlikely to result from an increase in the synthesis of selenoproteins.

PMID- 7514024
TI  - Analysis of the endocytic-lysosomal system (vacuolar apparatus) in astrocytes
      during proliferation and differentiation in primary culture.
AB  - The endocytic-lysosomal system of proliferating and differentiated astrocytes in
      primary culture was investigated using a combination of cytochemical,
      immunocytochemical and biochemical procedures. These included impregnation with
      osmium tetroxide and potassium iodide, phosphotungstic acid staining,
      cytochemical demonstration of acid phosphatase and thiamine pyrophosphatase
      activities and incorporation of cationized ferritin. The acid phosphatase
      activity was also analyzed using biochemical techniques. Our results indicate
      that while all astrocytes in primary culture have a developed endocytic-lysosomal
      system, this system is different in proliferating cells from that in
      differentiated astrocytes. Whereas in proliferating astrocytes it appears to be
      composed mainly of a variety of vacuoles and vesicles displaying a heterogeneous
      osmium tetroxide staining pattern, differentiated cells are characterized by the
      presence of small size vesicles showing an intense reaction. Both types of
      astrocyte showed abundant lysosomes, including multivesicular bodies, which
      presented an intense phosphatase acid activity. Biochemical analyses demonstrated
      that this activity increase during the proliferation period, reaching a maximum
      at 15 days of culture. Incorporation of cationized ferritin revealed that
      lysosomes and endosomes constitute separate systems. Finally, we have also found
      that the activity of thiamine pyrophosphatase, a marker for the Golgi complex,
      increases throughout the culture period. These results indicate that astrocytes
      could play an important role in regulating the macromolecular composition of the
      extracellular space.

PMID- 7514025
TI  - Expression of four growth factors during fracture repair.
AB  - Fracture repair offers an opportunity to study the physiology of bone formation
      at the fracture site. Isolation of growth factors from bone matrix has implicated
      growth factors as participants in bone physiology. We therefore examined the
      expression patterns of aFGF, IGF-I, PDGF, and TGF-beta during fracture repair. An
      animal model has been developed to study repair of tibial fractures. The model
      provides both reproducible and quantifiable results, allowing the fracture repair
      process to be divided into four stages (Bourque et al., Lab. Anim. Sci 42: 369
      374, 1992). Fractured tibiae were examined immunohistochemically with polyclonal
      antibodies to four growth factors. PDGF was visualized in macrophages in close
      proximity to the periosteum during stage 1. aFGF was visualized in cells of the
      expanded cambial layer and was associated with a rapid increase in the population
      of fibroblast-like mesenchymal cells during stage 2. IGF-I was visualized in
      young chondroblasts at the edge of the cartilage mass replacing the fibrous
      callus during stage 3. TGF-beta was visualized in calcified matrix producing
      chondrocytes at the edge of ossification fronts penetrating the cartilage callus
      during stage 4. The immunohistochemical results suggest that these growth factors
      act as local simulators of the repair process.

PMID- 7514026
TI  - Analyses of p53 antibodies in sera of patients with lung carcinoma define
      immunodominant regions in the p53 protein.
AB  - Antibodies specific for human p53 were analysed in sera of lung cancer patients.
      We detected p53 antibodies in the sera of 24% (10/42) of patients with lung
      carcinoma. The distribution was as follows: 4/9 small-cell lung carcinomas
      (SCLCs), 2/18 squamous cell lung carcinomas (SCCs), 2/10 adenocarcinomas (ADCs)
      and 2/5 large-cell lung carcinomas (LCCs). p53 antibodies were always present at
      the time of diagnosis and did not appear during progression of the disease. Using
      an original peptide-mapping procedure, we precisely localised the p53 epitopes
      recognised by p53 antibodies. Immunodominant epitopes reacting with antibodies
      were localised in the amino and carboxy termini of the protein, similar to those
      found in breast carcinoma patients or in animals immunised with p53. In light of
      these data, we suggest that p53 antibodies occur via a self-immunisation process
      that is the consequence of p53 accumulation in tumour cells. p53 antibodies were
      also detected in two patients without detected malignant disease. One of these
      patients died 6 months later of lung carcinoma, suggesting that p53 antibodies
      may be a precocious marker of p53 alteration.

PMID- 7514027
TI  - p53 immunohistochemical analysis in breast cancer with four monoclonal
      antibodies: comparison of staining and PCR-SSCP results.
AB  - The expression of p53 protein was examined in a series of 136 primary breast
      carcinomas, 106 of which were analysed with a panel of four monoclonal antibodies
      (MAbs 1801, 240, DO7 and DO1). p53 expression was detected with at least one
      antibody in 40 tumours (38%), whereas only 15 tumours (14%) were positive with
      all four antibodies. Some variability in the immunostaining could be observed
      depending on the antibody used. This was noticeable both for the number of
      positive cells within a section and for the intensity of staining. We therefore
      selected a panel of 17 tumour sections (nine were highly positive, three with
      medium to low staining and five with low to negative staining), which we analysed
      by polymerase chain reaction-single-strand conformation polymorphism analysis
      (PCR-SSCP) for the presence of a p53 mutation at the molecular level. Mutations
      were identified in 15 cases. Therefore the proportion of p53-stained cells does
      not seem to be an exact representation of the number of cancer cells bearing a
      mutation within a tumour. A statistically significant correlation was observed
      between p53 expression, regardless of the number of positive antibodies, and
      grade III disease (P < 0.0001), oestrogen (P < 0.0001) or progesterone receptor
      negativity (P = 0.0061), increased Ki 67 index (P = 0.0018), epidermal growth
      factor receptor (EGFR) positivity (P = 0.0076) and aneuploidy (P = 0.037). No
      correlation was observed with tumour size or lymph node involvement. In
      univariate analysis p53 expression was not correlated with disease-free survival,
      in contrast to the classical prognostic parameters, which were statistically
      correlated. In this series p53 expression was not a marker of early recurrence.

PMID- 7514028
TI  - A structure-activity analysis of antagonism of the growth factor and angiogenic
      activity of basic fibroblast growth factor by suramin and related polyanions.
AB  - The ability of a series of polysulphonated naphthylureas structurally related to
      suramin to inhibit basic fibroblast growth factor (bFGF) or serum-stimulated
      growth of endothelial cells [either large vessel, human umbilical vein
      endothelial cells (HUVEC) or microvascular, bovine adrenal capillary endothelial
      (BACE) cells] and angiogenesis in vivo has been examined. The polyanions
      encompassed two main structural variations, namely the number of aromatic amide
      groups intervening between two terminal naphthyl rings and/or variation in the
      substitution pattern of the naphthyl rings. The polyanions were either inactive
      (group I) or inhibited (group II) bFGF-stimulated uptake of [3H]methylthymidine
      by BACE cells. Group I compounds shared a common structural feature in that they
      were simple binaphthyl-substituted ureas. In contrast, group II compounds all had
      an extended multiple ring structure with at least two aromatic groups intervening
      between the two terminal naphthyl rings. Compounds with either two or four
      intervening groups were equipotent in blocking bFGF in vitro. However, compounds
      with two bridging aromatic groups were 5- to 10-fold less toxic than suramin in
      mice, suggesting a potential for an improved therapeutic ratio. The ability of
      the polyanions to block bFGF-driven endothelial cell proliferation in vitro
      correlated with antiangiogenic activity in vivo as shown by use of the rat sponge
      angiogenesis model. These observations could substantially widen the anti-tumour
      therapeutic opportunities for this class of compound.

PMID- 7514029
TI  - Prostatic carcinoma: a multivariate analysis of prognostic factors.
AB  - Tissue specimens from 150 patients with localised prostatic carcinomas and 116
      patients with prostatic carcinomas with distant metastases were analysed for
      histological grade (WHO and Gleason) and immunoreactivity for prostate acid
      phosphatase (PAP), prostate-specific antigen (PSA), neurone-specific enolase
      (NSE), p53 protein, c-erbB-2 protein, cytokeratins (AE1/AE3) and vimentin. After
      stratification for the presence or absence of distant metastases, multivariate
      regression analysis revealed that WHO grading was the most powerful independent
      prognosticator, followed by age and prostate acid phosphatase expression. There
      was a trend towards reduced survival with decreasing prostate-specific antigen
      reactivity. The Gleason system showed poor prognostic ability. The analysis
      predicted reduced survival in the presence of extensive neurone-specific enolase
      reactivity, mostly because of one case of small-cell carcinoma.

PMID- 7514030
TI  - The intramuscular administration of granulocyte colony-stimulating factor as an
      adjunct to chemotherapy in pretreated ovarian cancer patients: an Italian Trials
      in Medical Oncology (ITMO) Group pilot study.
AB  - No published data are available concerning the activity and tolerability of
      intramuscularly administered granulocyte colony-stimulating factor (G-CSF) in
      humans. To fill this gap, 19 patients with advanced ovarian cancer previously
      treated with at least one first-line chemotherapy cycle received the following
      myelosuppressive regimen: mitoxantrone (DHAD) 12 mg m-2 i.v. on day 1; ifosfamide
      (IFO) 4 g m-2 i.v. on days 1 and 2; mesna 800 mg m-2 i.v. t.i.d. on days 1 and 2.
      G-CSF (Filgrastim) was given at a dose of 5 micrograms/kg/day i.m. from day 6 to
      day 19, its pharmacokinetics being assessed in five patients. The neutrophil
      nadir was observed after a mean period of 8 days, and the neutrophil count was <
      1.0 x 10(3) mm-3 for a mean of 6 days during the cycle of chemotherapy. The
      neutrophil count fell after the withdrawal of G-CSF on the 19th day of treatment.
      The difference in absolute neutrophil count between day 19 and day 21 was
      statistically significant (P = 0.0001); nevertheless, at day 21 no WHO grade 3-4
      neutropenia was reported. DHAD and IFO were respectively given at 95% and 93% of
      the planned dose. The pharmacokinetics of G-CSF i.m. seems to be similar to that
      of the drug given subcutaneously. No evidence of cumulative myelosuppression was
      observed. G-CSF was well tolerated and no complications were observed at the
      injection sites. In conclusion, if the results obtained in this pilot study
      regarding the activity of i.m. G-CSF are confirmed by a randomised trial, the
      intramuscular administration of G-CSF could become a valid alternative for
      patients who dislike the subcutaneous route and who are being treated with
      chemotherapy that does not induce profound thrombocytopenia.

PMID- 7514032
TI  - Antagonistic effects of retinoic acid and triiodothyronine in the expression of
      corticoid-binding globulin (CBG) by cultured fetal hepatocytes.
AB  - Cultures of rat fetal hepatocytes were used to investigate the effects and
      interplay of triiodothyronine (T3) and retinoic acid (RA) in the regulation of
      gene expression of CBG, compared to that of alpha-fetoprotein (AFP). The cultured
      cells showed cytological features typical to hepatocytes and actually synthesized
      CBG and AFP, as evidenced from in situ hybridization with specific radioactive
      probes. Time course studies indicated that CBG (but not AFP) binding capacity in
      culture medium and cell mRNA levels disappeared with a half-life of about 2 days,
      thereby reflecting the decrease previously seen in hepatic CBG mRNA contents
      during embryonic life. The Kd values for CBG binding were unchanged under these
      conditions. Culturing of hepatocytes in the presence of T3 resulted in dose
      dependent stimulations of both medium CBG and cell mRNA levels, with an EC50
      concentration of about 10(-9) M. In sharp contrast, RA caused a reduction in CBG
      biosynthesis (IC50 = 1.7 x 10(-7) M) and, in addition, antagonized the
      stimulatory influence of T3. Under the same experimental conditions, AFP
      synthesis failed to be affected in a similar fashion. We conclude that thyroid
      hormones and RA directly act on hepatocytes to specifically regulate the
      expression of CBG in an antagonistic way.

PMID- 7514031
TI  - Effects of ultraviolet B radiation on cytoskeletal and adhesion molecules in
      human epidermis.
AB  - The expression of cytokeratins (CK), various adhesion molecules and growth factor
      receptors were investigated in ultraviolet (UV) erythemas 24 h and 48 h after
      exposure to 4 times the minimal erythema dose. Skin biopsies were analysed
      immunohistochemically using a battery of antibodies and biochemically by gel
      electrophoresis. The CK pattern was shown to change within 24 h. CK typical of
      basal keratinocytes were detectable heterogeneously within the suprabasal
      compartment, and the staining for suprabasal CK was heterogeneous in prickle
      cells. Interestingly, CK 17, not detectable in normal epidermis, was induced
      within a few hours in suprabasal cells but not in basal ones. In addition, CK 6
      and 16, typical for hyperproliferation, were intensively synthesized in all
      epidermal layers already 24 h after UV exposure. Moreover, integrin expression
      was studied and surprisingly integrins were heterogeneously detectable, the
      staining being patchy in suprabasal keratinocytes and reduced within the basal
      layer. Receptors of epidermal growth factor and nerve growth factor were
      distributed in UV erythema very irregularly and weakly. Our findings argue for
      profound changes in composition of cytoskeleton and of cell adhesion molecules in
      the epidermis shortly after UV exposure.

PMID- 7514033
TI  - Stromal expression of tenascin is inversely correlated to epithelial
      differentiation of hormone dependent tissues.
AB  - We were previously investigating the expression of the extracellular matrix
      glycoprotein tenascin in normal and malignant endometrial tissues of humans and
      rodents. These studies suggested that the expression of tenascin was induced by
      proliferating epithelia (normal and particularly malignant) and was downregulated
      with their differentiation. The aim of this study was to investigate the hormone
      dependency of tenascin expression in (a) the transplantable EnDA endometrial
      tumor model with or without estrogen deprivation (ovariectomy) of the animals,
      (b) DMBA-induced rat mammary tumors with or without a hormonal treatment of the
      animals [ovariectomy, antiestrogen (tamoxifen) or antiprogestin (ZK 98299)
      treatment] and (c) in the rat prostate of untreated or androgen deprived animals
      (orchiectomy, flutamide-, casodex- or cyproterone acetate (CPA)-treatment). 1.
      Estrogen withdrawal by ovariectomy did not affect tenascin expression in
      transplantable EnDA endometrial adenocarcinoma, meaning the entire extracellular
      space of the stromal mesenchyme was decorated by tenascin immunoreactivity. 2. In
      untreated DMBA-induced rat mammary tumors almost the entire extracellular space
      of the stroma was stained by tenascin immunoreactivity. Ovariectomy and
      antiestrogen treatment did not affect tenascin expression. In contrast,
      antiprogestin treatment induced terminal differentiation of mammary tumor cells
      and in parallel downregulated tenascin expression. 3. In the normal rat prostate
      no tenascin was detectable by immunocytochemistry. However, following androgen
      deprivation we found tenascin expression in the stroma of the prostate. The most
      prominent expression was observable after CPA-treatment, possibly due to its
      progestagenic potency. In conclusion, the hormones and antihormones tested show
      no direct effect on the stromal expression of tenascin. However, proliferative
      activity and a low degree of differentiation of the epithelium induces tenascin
      expression, whereas epithelial differentiation apparently shuts down tenascin
      expression. Preliminary in vitro studies suggest that paracrine acting growth
      factors trigger the hormonal regulation of tenascin expression.

PMID- 7514034
TI  - Critical issues of developmental seizure disorders.

PMID- 7514035
TI  - A monoclonal antibody to human angiogenin. Inhibition of ribonucleolytic and
      angiogenic activities and localization of the antigenic epitope.
AB  - A monoclonal antibody (mAb) to human angiogenin, a protein that induces formation
      of new blood vessels, was produced by somatic cell fusion techniques and
      designated as 26-2F. It is an IgGl kappa whose binding affinity, expressed as an
      IC50, is (1.6 +/- 0.1) x 10(-9) M as determined by a competition
      radioimmunoassay. mAb 26-2F neutralizes the ribonucleolytic activity of
      angiogenin as assessed by in vitro protein synthesis and tRNA degradation assays.
      It also effectively inhibits neovascularization induced by angiogenin on the
      chick chorioallantoic membrane. Epitope mapping indicates that the binding region
      of angiogenin recognized by mAb 26-2F is discontinuous and involves both Trp-89
      and residues in the segment 38-41. This epitope is formed by two surface loops
      which are juxtaposed in the three-dimensional structure of human angiogenin
      recently determined by X-ray crystallography. Thus mAb 26-2F, along with similar
      antibodies under investigation, will facilitate structure/function studies of
      angiogenin, help define its physiological role, and lead to an understanding of
      the consequences of its inhibition in pathological situations in which angiogenin
      may be involved.

PMID- 7514036
TI  - Homogeneous aggregation of the 14-kDa beta-galactoside specific vertebrate lectin
      complex with asialofetuin in mixed systems.
AB  - The galactose-specific 14-kDa family of animals lectins are an evolutionary
      conserved group of proteins that have been implicated in a wide variety of
      biological processes including cell proliferation, adhesion, and transformation.
      The present study demonstrates that the dimeric 14-kDa calf spleen lectin forms
      homogeneous aggregated cross-linked complexes with asialofetuin, a glycoprotein
      with multiple carbohydrate chains possessing terminal galactose residues, in the
      presence of other lectins with similar specificities and cross-linking
      activities. Several galactose-specific plant lectins also form homogeneous
      aggregated cross-linked complexes with ASF. These results demonstrate a new
      source of specificity for the 14-kDa family of vertebrate lectins, namely, the
      ability to selectively cross-link and aggregate glycoproteins in mixed systems.
      The results have important biological implications for the interactions of
      multivalent lectins and glycoconjugates, as well as the thermodynamic
      interactions of multivalent molecules in general.

PMID- 7514037
TI  - Neuromodulin (GAP-43) can regulate a calmodulin-dependent target in vitro.
AB  - The calmodulin-binding polypeptide neuromodulin (GAP-43) was tested in vitro for
      its ability to modulate a typical calmodulin target, the enzyme nitric oxide
      synthase. The titration of enzyme with increasing neuromodulin concentrations
      demonstrated a concentration-dependent decrease in enzyme activity. Subsequent
      analysis of the ability of increased calcium concentrations to activate the
      enzyme was tested in the presence or absence of neuromodulin. The effect of
      neuromodulin on the calcium-dependent activation of the enzyme was to depress
      enzyme activity in the range of 0.2 to approximately 6 microM calcium. Treatment
      of the neuromodulin polypeptide with protein kinase C eliminated its ability to
      inhibit nitric oxide synthase activation. Subsequent treatment of the
      phosphorylated neuromodulin with calcineurin (phosphatase 2b) caused it to regain
      its inhibitory action on the enzyme. The results from these in vitro studies have
      indicated that neuromodulin has the ability to affect the activation of a
      calmodulin-dependent enzyme at levels of the polypeptide that exist in neurons.
      They also demonstrated that the regulation occurred within a physiological range
      of calcium concentrations. Since the inhibition of enzyme activity appeared to be
      occurring through the interaction of neuromodulin with calmodulin, it seems
      likely that neuromodulin has a general ability to impede activation of calmodulin
      dependent targets.

PMID- 7514038
TI  - Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance
      calcium-activated potassium channels.
AB  - Tremorgenic indole alkaloids produce neurological disorders (e.g., staggers
      syndromes) in ruminants. The mode of action of these fungal mycotoxins is not
      understood but may be related to their known effects on neurotransmitter release.
      To determine whether these effects could be due to inhibition of K+ channels, the
      interaction of various indole diterpenes with high-conductance Ca(2+)-activated
      K+ (maxi-K) channels was examined. Paspalitrem A, paspalitrem C, aflatrem,
      penitrem A, and paspalinine inhibit binding of [125I]charybdotoxin (ChTX) to maxi
      K channels in bovine aortic smooth muscle sarcolemmal membranes. In contrast,
      three structurally related compounds, paxilline, verruculogen, and paspalicine,
      enhanced toxin binding. As predicted from the binding studies, covalent
      incorporation of [125I]ChTX into the 31-kDa subunit of the maxi-K channel was
      blocked by compounds that inhibit [125I]ChTX binding and enhanced by compounds
      that stimulate [125I]ChTX binding. Modulation of [125I]ChTX binding was due to
      allosteric mechanisms. Despite their different effects on binding of [125I]ChTX
      to maxi-K channels, all compounds potently inhibited maxi-K channels in
      electrophysiological experiments. Other types of voltage-dependent or Ca(2+)
      activated K+ channels examined were not affected. Chemical modifications of
      paxilline indicate a defined structure-activity relationship for channel
      inhibition. Paspalicine, a deshydroxy analog of paspalinine lacking tremorgenic
      activity, also potently blocked maxi-K channels. Taken together, these data
      suggest that indole diterpenes are the most potent nonpeptidyl inhibitors of maxi
      K channels identified to date. Some of their pharmacological properties could be
      explained by inhibition of maxi-K channels, although tremorgenicity may be
      unrelated to channel block.

PMID- 7514040
TI  - Studies on the induction of cyclooxygenase isozymes by various prostaglandins in
      mouse osteoblastic cell line with reference to signal transduction pathways.
AB  - A mouse osteoblastic cell line MC3T3-E1 has a cyclooxygenase enzyme, and produces
      prostaglandin E2. When the cells were cultured in the presence of iloprost (a
      stable analogue of prostacyclin) or prostaglandin E1 or F2 alpha, the activity of
      cyclooxygenase increased in a dose- and time-dependent manner. The increase of
      the enzyme activity was attributed mostly to the cyclooxygenase isoform-2 because
      immunoprecipitation using an anti-cyclooxygenase-2 antibody removed the majority
      of the cyclooxygenase activity from the solubilized enzyme fraction, and the
      corresponding activity was detected in the immunoprecipitant. In addition, there
      was a marked increase in the cyclooxygenase-2 protein which was demonstrated by
      Western blotting. As analyzed by Northern blotting, the cyclooxygenase-2 mRNA
      increased and reached a maximum 1 and 3 h after the addition of iloprost and
      prostaglandin F2 alpha (about 15- and 60-fold increase), respectively, whereas
      the cyclooxygenase-1 mRNA increased slowly and only by about 3-fold. Iloprost and
      prostaglandin E1 stimulated the production of cAMP by 60-fold over the basal
      level, whereas the cAMP level was almost unchanged by prostaglandin F2 alpha. In
      contrast, prostaglandin F2 alpha stimulated IP3 production more efficiently than
      iloprost and prostaglandin E1. These results suggest that the stimulated
      syntheses prominently of cyclooxygenase-2 and to a lesser extent of
      cyclooxygenase-1 are mediated by at least two distinct signal transduction
      pathways involving the cAMP-synthesis stimulated by iloprost and prostaglandin E1
      and the phosphoinositide turnover stimulated by prostaglandin F2 alpha.

PMID- 7514039
TI  - Backbone dynamics of a free and phosphopeptide-complexed Src homology 2 domain
      studied by 15N NMR relaxation.
AB  - The backbone dynamics of the C-terminal SH2 domain of phospholipase C gamma 1
      have been investigated. Two forms of the domain were studied, one in complex with
      a high-affinity binding peptide derived from the platelet-derived growth factor
      receptor and the other in the absence of this peptide. 2-D 1H-15N NMR methods,
      employing pulsed field gradients, were used to determine steady-state 1H-15N NOE
      values and T1 and T2 15N relaxation times. Backbone dynamics were characterized
      by the overall correlation time (tau m), order parameters (S2), effective
      correlation times for internal motions (tau e), and, if required, terms to
      account for motions on a microsecond-to-millisecond-time scale. An extended two
      time-scale formalism was used for residues having relaxation data and that could
      not be fit adequately using a single-time-scale formalism. The overall
      correlation times of the uncomplexed and complexed forms of SH2 were found to be
      9.2 and 6.5 ns, respectively, suggesting that the uncomplexed form is in a
      monomer-dimer equilibrium. This was subsequently confirmed by hydrodynamic
      measurements. Analysis of order parameters reveals that residues in the so-called
      phosphotyrosine-binding loop exhibited higher than average disorder in both forms
      of SH2. Although localized differences in order parameters were observed between
      the uncomplexed and complexed forms of SH2, overall, higher order parameters were
      not found in the peptide-bound form, indicating that on average, picosecond-time
      scale disorder is not reduced upon binding peptide. The relaxation data of the
      SH2-phosphopeptide complex were fit with fewer exchange terms than the
      uncomplexed form. This may reflect the monomer-dimer equilibrium that exists in
      the uncomplexed form or may indicate that the complexed form has lower
      conformational flexibility on a microsecond-to-millisecond-time scale.

PMID- 7514041
TI  - Melanotic neuroectodermal tumor of infancy. Report of a case.
AB  - A case of melanotic neuroectodermal tumor of infancy involving the right
      maxillary alveolar ridge region of a 4 month old girl is reported. Clinical,
      histopathological and laboratory findings supported the diagnosis. This case had
      high levels of urinary excretion of vanilmandelic acid (2.8 mg/24 hrs.) and serum
      alpha-fetoprotein (210 mg/ml); which are characteristic of this tumor.

PMID- 7514043
TI  - Antithrombin III infusion suppresses the hypercoagulable state in adult acute
      lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L
      asparaginase. A GIMEMA study.
AB  - Thrombotic events have been reported in acute lymphoblastic leukaemia patients,
      especially during or after L-asparaginase administration. A so-called L
      asparaginase associated coagulopathy has been well recognized, being
      characterized by a hypercoagulable state (decrease of antithrombin III,
      plasminogen, protein C, protein S and increase of prothrombin fragment F1 + 2,
      thrombin-antithrombin complexes and fibrinopeptide A). The aim of this study was
      to determine whether the supplementation of antithrombin III (AT-III)
      concentrates could improve the L-asparaginase associated coagulopathy, thereby
      blocking the activation of the haemostatic system. In 25 adult patients with
      acute lymphoblastic leukaemia (M 19, F6, mean age 34 years) antithrombin III (AT
      III) concentrates were administered at daily doses of 50 U/kg for 10 consecutive
      days from the beginning of L-asparaginase therapy (6,000 U/m2/day s.c. for 7
      days), given according to the GIMEMA ALL 0288 trial. A marked increase of
      antithrombin III was recorded on days IV-VIII-XI (P < 0.001). No changes in
      protein C, protein S, plasminogen, alpha 2-antiplasmin, factor VII and platelet
      count were observed and there was no increase in markers of hypercoagulability.
      There was no evidence of disseminated intravascular coagulation. In conclusion,
      AT-III concentrate supplementation during L-asparaginase therapy, by the
      achievement of high levels of antithrombin III, is associated with a lack of
      activation of the haemostatic system and appears to overcome the complex
      coagulopathy associated with L-asparaginase.

PMID- 7514044
TI  - Levels of fibrinolytic activators and inhibitors in plasma after severe trauma.
AB  - Levels of tissue plasminogen activator antigen (t-PA:ag), tissue plasminogen
      activator inhibitor 1 antigen (PAI-1:ag) and tissue plasminogen activator
      inhibitor activity (PAI activity), and alpha-2-antiplasmin (AAP) were measured in
      plasma from 19 patients with severe trauma on admission and on days 1, 2, 3 and 7
      after the incident. In all patients the Injury Severity Score (ISS) and the
      number of blood transfusions were recorded. The development of post-traumatic
      pulmonary dysfunction was observed in four patients. Levels of t-PA:ag, PAI-1:ag
      and PAI activity were increased, and levels of AAP were low immediately after
      trauma. Levels of t-PA:ag normalized during the first week, whereas PAI-1:ag
      levels decreased gradually from day 1 to day 3. Thereafter a secondary increase
      was observed. A similar trend was observed in levels of PAI activity. Levels of
      APP increased significantly during the first week. t-PA:ag, PAI-1:ag or PAI
      activity levels were not correlated with the ISS on any day, but levels of AAP
      showed a weak correlation with the ISS on day 7. Post-traumatic levels of t-PA:ag
      and PAI-1:ag were higher in patients who had 6 or more units of blood
      transfusions for resuscitation. The fibrinolytic markers were not significantly
      different in patients who had pulmonary dysfunction compared with patients
      without.

PMID- 7514042
TI  - Continuing development of acid pump inhibitors: site of action of pantoprazole.
AB  - Both receptor antagonists and acid pump inhibitors are clinically useful
      suppressants of acid secretion. The latter class of drugs, the substituted
      benzimidazoles, inhibit acid secretion more effectively and, therefore, provide
      superior symptom relief and healing in all acid-related diseases. The H2-receptor
      antagonists competitively block the action of histamine on the H2-receptors of
      parietal cells. This histamine is released from enterochromaffin-like cells (ECL
      cells) due to gastrin, acetylcholine or epinephrine stimulation. In addition,
      parietal cells have M3-receptors which can function independently of H2
      receptors. Hence, there is no single common pathway for parietal cell
      stimulation. Stimulation of acid secretion by parietal cells requires activation
      of the acid pump, the gastric H+,K(+)-ATPase. The target site for the
      benzimidazoles is the activated gastric H+,K(+)-ATPase, and, in particular, the
      cysteines of the pump that are exposed to the acid space of the secretory
      canaliculus of the parietal cells. Pantoprazole in its protonated form
      selectively reacts with cysteines present in both the fifth and sixth membrane
      segments of the ATPase, explaining its mechanism of inhibiting proton transport
      by this enzyme.

PMID- 7514045
TI  - Inhibition of human B-cell lymphoma growth by CD40 stimulation.
AB  - CD40 is a molecule present on B lymphocyte lineage cells that is important in B
      cell differentiation and activation. Signaling through CD40 has been shown to
      exert costimulatory signals on normal B cells resulting in proliferative and
      differentiation responses. Examination of several B-cell lymphomas showed cell
      surface expression of the CD40 molecule. Incubation of these lymphomas with anti
      CD40 antibodies resulted in significant growth inhibition in vitro. Cross-linking
      of the CD40 antibodies resulted in even greater inhibition of proliferation. A
      recombinant soluble human CD40 ligand was also shown to inhibit lymphoma
      proliferation. When various human B-cell lymphomas were transferred into mice
      with severe combined immune deficiency, the treatment of the mice with anti-CD40
      antibodies resulted in significant increases in survival showing that anti-CD40
      is efficacious after in vivo administration. Thus, CD40 stimulation by either the
      antibody or soluble ligand directly inhibits human B-cell lymphoma growth and
      therefore, may be of significant clinical use in their treatment.

PMID- 7514047
TI  - Differential regulation of stem cell factor mRNA expression in human endothelial
      cells by bacterial pathogens: an in vitro model of inflammation.
AB  - Production of hematopoietic growth factors by endothelial cells plays a pivotal
      role during inflammatory processes. Stem cell factor (SCF) is known to be
      expressed constitutively in endothelial cells. To investigate the regulation of
      this cytokine expression by inflammatory stimuli, we cocultured human umbilical
      vein endothelial cells (HUVEC) with various gram-negative bacterial strains
      (Escherichia coli, Yersinia enterocolitica, Chlamydia trachomatis, and Neisseria
      meningitidis, respectively). Experiments were performed with bacterial
      concentrations ranging from 10(2) to 10(7) bacteria/mL for 3 hours. SCF-specific
      mRNA expression was studied using Northern blot analysis. Stimulation with the
      enteropathogenic bacterial strains Y enterocolitica and E coli resulted in a
      significant concentration-dependent increase of SCF mRNA expression. Similar
      results were obtained in coculture experiments with N meningitidis. As shown in
      experiments with E coli, the accumulation of SCF transcripts was also time
      dependent. In contrast, coculture of HUVEC with the intracellular gram-negative
      strain C trachomatis had no effect on SCF mRNA expression. To elucidate the role
      of the gram-negative bacterial cell wall components, we stimulated HUVEC with
      bacterial lipopolysaccharide (LPS). LPS induced a maximal SCF mRNA accumulation
      within 2 hours followed by decrease of SCF-specific transcripts to the basal
      level after 24 hours. In addition, we exposed HUVEC to the classical inflammatory
      cytokine interleukin-1 alpha (IL-1 alpha). Kinetic experiments showed a similar
      pattern of regulation with an increase of SCF mRNA within 2 hours, persisting up
      to 12 hours, and a decrease to basal transcription after 24 hours. From these
      data, we conclude that SCF expression is regulated by inflammatory stimuli, such
      as IL-1 alpha and bacterial pathogens, suggesting an important role of SCF during
      inflammation.

PMID- 7514046
TI  - A randomized study of erythropoietin and granulocyte colony-stimulating factor (G
      CSF) versus placebo and G-CSF for patients with Hodgkin's and non-Hodgkin's
      lymphoma undergoing autologous bone marrow transplantation.
AB  - Anemia is a universal finding in patients undergoing autologous bone marrow
      transplantation (BMT). Effective therapies to increase the number of autologous
      red blood cells could result in a lower morbidity and mortality associated with
      red blood cell transfusions. We examined whether the addition of erythropoietin
      (Epo) to intensive therapy supported by progenitor cell transplantation and
      granulocyte colony-stimulating factor (G-CSF) would result in a lower requirement
      for red blood cell transfusions. Thirty-five patients with lymphoma were
      randomized to receive Epo versus placebo. Epo (600 U/kg three times per week) or
      placebo was begun 3 weeks before administration of high-dose therapy. Epo was
      held during the week of the preparatory regimen, and restarted on the day after
      BMT. All patients also received G-CSF following BMT. No significant differences
      were noted between the two groups in terms of patient characteristics at
      pretreatment or post-BMT evaluation. There were no differences in the total
      number of red blood cell units transfused (median Epo: 8 v placebo: 6, P = .22)
      nor the number of platelet transfusions given (median Epo: 12 v placebo 5, P =
      .14). Engraftment of granulocytes (absolute neutrophil count > or = 500/microL)
      occurred in a median of 12 days (range, 9 to 33) for the patients receiving Epo
      and G-CSF, compared with a median of 10 days (range, 8 to 22) for those receiving
      placebo and G-CSF (P = .70). Likewise, there were no differences in the time to
      platelet count > or = 20,000/microL without further transfusions with a median of
      22 days (range, 15 to 150+) for those receiving Epo and G-CSF compared with a
      median of 20 days (range, 11 to 54) for those patients receiving placebo and G
      CSF (P = .28). The combination of G-CSF and Epo as administered in this study
      appears to be safe but does not result in an improvement in the total number of
      red blood cell transfusions or total number of single donor platelet units
      transfused.

PMID- 7514048
TI  - Roles for integrin very late activation antigen-4 in stroma-dependent
      erythropoiesis.
AB  - Adhesion molecules are required for development of hematopoietic stem and
      progenitor cells in the respective hematopoietic microenvironments. We previously
      showed that development of the erythroid progenitor cells is dependent on their
      direct adhesion to the stroma cells established from the erythropoietic organs.
      In this stroma-dependent erythropoiesis, we examined the role of adhesion
      molecules in erythropoiesis by blocking antibodies. The development of the
      erythroid cells on stroma cells was inhibited by anti-very late activation
      antigen-4 (VLA-4 integrin) antibody, but not by anti-VLA-5 antibody, although the
      erythroid cells express both VLA-4 and VLA-5. Whereas high levels of expression
      of vascular cell adhesion molecule-1 (VCAM-1) and fibronectin, ligands for VLA-4,
      were detected in the stroma cells, the adhesion and development of the erythroid
      progenitor cells were partly inhibited by the blocking antibody against VCAM-1.
      VLA-5 and fibronectin could mediate adhesion of the erythroid progenitor cells to
      the stromal cells, but the adhesion itself may not be sufficient for the stroma
      supported erythropoiesis. The stromal cells may support erythroid development by
      the adhesion through a new ligand molecule(s) for VLA-4 in addition to VCAM-1,
      and such collaborative interaction may provide adequate signaling for the
      erythroid progenitor cells in the erythropoietic microenvironment.

PMID- 7514049
TI  - Platelet adhesion to collagen in individuals lacking glycoprotein IV.
AB  - The Naka isoantigen is expressed on glycoprotein (GP) IV (CD36), a platelet
      membrane GP that has been identified as having a role in platelet interactions
      with collagen and thrombospondin and in binding Plasmodium falciparum-infected
      erythrocytes to endothelial cells and melanoma cells. We have studied normal
      platelets and Naka- platelets from two Japanese donors that have 1% of GPIV by
      concentration-dependent antibody binding and flow cytometry. We studied the
      adherence of normal and Naka- platelets to types I, III, and IV collagen in
      static and to type I collagen in flowing systems at high shear force. We have
      also studied aggregation of normal and Naka- platelets to type I collagen. Naka-
      platelets showed normal or increased aggregation to type I collagen and normal
      adhesion to types I, III, and IV collagen in the presence of Mg++ or EDTA.
      Platelet aggregation and adhesion were inhibited by the anti-alpha 2 beta 1
      antibody 176D7 to the same extent in Naka- as in normal platelets. We also
      studied endogenous thrombospondin surface expression and found that thrombin
      stimulated Naka- platelets expressed the same amount of thrombospondin as did
      normal platelets. From our studies with Naka- platelets, we cannot identify a
      definitive role for GPIV in platelet aggregation, in adhesion to types I, III,
      and IV collagen, or in endogenous thrombospondin binding to platelets.

PMID- 7514050
TI  - Sustained human hematopoiesis in immunodeficient mice by cotransplantation of
      marrow stroma expressing human interleukin-3: analysis of gene transduction of
      long-lived progenitors.
AB  - We have developed a novel cotransplantation system in which gene-transduced human
      CD34+ progenitor cells are transplanted into immunodeficient (bnx) mice together
      with primary human bone marrow (BM) stromal cells engineered to produce human
      interleukin-3 (IL-3). The IL-3-secreting stroma produced sustained circulating
      levels of human IL-3 for at least 4 months in the mice. The IL-3-secreting
      stroma, but not control stroma, supported human hematopoiesis from the
      cotransplanted human BM CD34+ progenitors for up to 9 months, such that an
      average of 6% of the hematopoietic cells removed from the mice were of human
      origin (human CD45+). Human multilineage progenitors were readily detected as
      colony-forming units from the mouse marrow over this time period. Retroviral
      mediated transfer of the neomycin phosphotransferase gene or a human
      glucocerebrosidase cDNA into the human CD34+ progenitor cells was performed in
      vitro before cotransplantation. Human multilineage progenitors were recovered
      from the marrow of the mice 4 to 9 months later and were shown to contain the
      transduced genes. Mature human blood cells marked by vector DNA circulated in the
      murine peripheral blood throughout this time period. This xenograft system will
      be useful in the study of gene transduction of human hematopoietic stem cells, by
      tracing the development of individually marked BM stem cells into mature blood
      cells of different lineages.

PMID- 7514051
TI  - Genetic marking shows that Ph+ cells present in autologous transplants of chronic
      myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in
      CML.
AB  - Relapse after autologous bone marrow transplantation for chronic myelogenous
      leukemia (CML) can be due either to the persistence of leukemia cells in systemic
      tissues following preparative therapy, or due to the persistence of leukemia
      cells in the autologous marrow used to restore marrow function after intensive
      therapy. To help distinguish between these two possible causes of relapse, we
      used safety-modified retroviruses, which contain the bacterial resistance gene
      NEO, to mark autologous marrow cells that had been collected from patients early
      in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were
      then subjected to ex vivo CD34 selection following collection and 30% of the bone
      marrow were exposed to a safety-modified virus. This marrow was infused after
      delivery of systemic therapy, which consisted of total body irradiation (1,020
      cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific
      for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl
      mRNA showed that in two evaluable CML patients transplanted with marked cells,
      sufficient numbers of leukemia cells remained in the infused marrow to contribute
      to systemic relapse. In addition, both normal and leukemic cells positive for the
      retroviral transgenome persisted in the systemic circulation of the patients for
      at least 280 days posttransplant showing that the infused marrow was responsible
      for the return of hematopoiesis following the preparative therapy. This
      observation shows that it is possible to use a replication-incompetent safety
      modified retrovirus in order to introduce DNA sequences into the hematopoietic
      cells of patients undergoing autologous bone marrow transplantation. Moreover,
      this data suggested that additional fractionation procedures will be necessary to
      reduce the probability of relapse after bone marrow transplantation in at least
      the advanced stages of the disease in CML patients undergoing autologous bone
      marrow transplantation procedures.

PMID- 7514052
TI  - CD7 expression does not affect the prognosis in acute myeloid leukemia.

PMID- 7514053
TI  - High expression of APO-1 (CD95) on T lymphocytes from human immunodeficiency
      virus-1-infected children.

PMID- 7514054
TI  - A study of the effects of human blood derivatives and individual growth factors
      on [3H]thymidine uptake in bovine retinal pericytes and endothelial cells.
AB  - Pericytes disappear early, selectively and specifically from retinal capillaries
      in diabetic microangiopathy, but little is known of their growth and turnover in
      health and disease. We have studied the effects of human blood derivatives and of
      a panel of individual growth factors on [3H]thymidine incorporation in bovine
      retinal pericytes and endothelial cells. Human serum and platelet-rich plasma
      stimulated incorporation of the nucleotide in a dose-dependent manner in both
      cell types, and did so more potently than platelet-free plasma. Consistent and
      significant stimulation of DNA synthesis in pericytes was observed with basic
      fibroblast growth factor (ED50 = 1.8 x 10(-13) mol/l), acidic fibroblast growth
      factor (7.4 x 10(-12) mol/l), insulin-like growth factor 1 (8.6 x 10(-10) mol/l),
      insulin (158 microU/ml) and endothelin-1 (6.1 x 10(-10) mol/l). Transforming
      growth factor beta 1 inhibited DNA synthesis (ID50 = 3.6 x 10(-10) mol/l) and so
      did heparin (1.4 x 10(-6) mol/l) and low molecular weight heparin (2.9 x 10(-6)
      mol/l). Retinal endothelial cells were stimulated by basic fibroblast growth
      factor (3.2 x 10(-13) mol/l) and acidic fibroblast growth factor (1.3 x 10(-9)
      mol/l), and inhibited by transforming growth factor beta 1 (1.6 x 10(-12) mol/l).
      Neither cell type was stimulated by platelet-derived growth factor (A + B chain
      heterodimer), epidermal growth factor, growth hormone, or nerve growth factor (7S
      complex). The characteristics and active concentrations of the above growth
      factors suggest that none is solely responsible for the pericyte mitogenic
      activity of platelets, serum or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514055
TI  - Human CD4 "internal antigen" mimicry by anti-idiotypic monoclonal antibodies.
AB  - Of 1019 hybridomas generated from a BALB/c mouse immunized with the syngeneic
      anti-CD4 monoclonal antibody HP2/6, 3 were found to secrete anti-idiotypic
      antibodies. Detailed analysis of anti-idiotypic monoclonal antibodies F16-10F6,
      F16-14D6 and F16-16D7 showed they recognize idiotope(s) not expressed by any of
      the anti-CD4 monoclonal antibodies tested, including those which inhibit the
      binding of HP2/6 to CD4 antigen. The idiotope recognized by the three anti
      idiotypic antibodies are within (or closely related to) the antigen combining
      site of the immunizing antibody and distinct and spatially distant from the
      idiotope defined by monoclonal antibody F11-2302 which was previously shown to be
      outside the antigen combining site of HP2/6. Although F16-14D6 and F16-16D7 are
      indistinguishable in isotype, binding titer to idiotopes, fine specificity on a
      panel of monoclonal antibodies, relation to the combining site and competitive
      binding, it is likely that they are structurally different and recognize two
      distinct combining site-related idiotopes on HP2/6, as they display different
      spectrotypes and induce anti-anti-idiotypic (Ab3) immune sera with different
      specificities. Analysis of the fine specificity of the two Ab3 immune sera
      suggest they share idiotopes with HP2/6 and contain antibodies reacting with CD4
      antigen. Among the latter, those induced with F16-14D6 display a different CD4
      epitope specificity than HP2/6. Hence, anti-idiotypic antibodies F16-14D6 and F16
      16D7 behave as "network antigen" for human CD4; idiotope-triggered antibody
      cascade may have a role in changing the specificities of antibody.

PMID- 7514056
TI  - Maternal serum markers. Estimation of the risk of Down's syndrome: a prospective
      study.
AB  - The risk of Down's syndrome pregnancies can be estimated by quantitation of
      maternal serum markers, namely alpha-fetoprotein, unconjugated estriol and human
      chorionic gonadotropin (triple test). A prospective study of 2892 pregnant women
      (median age 33.5 years) is reported. The detection rate of Down's syndrome
      pregnancies was 80% (confidence intervals 45%-100%) when a risk of 1:380 or
      greater was considered "screen positive", the false positive rate was 13.3%
      (confidence intervals 12.0%-14.5%). The importance of the accurate assessment of
      gestational age and the time of blood sampling are emphasized. Our findings are
      compared with similar studies performed in other laboratories.

PMID- 7514058
TI  - Development of pseudolymphoma of liver following interferon-alpha therapy for
      chronic hepatitis B.
AB  - A 42-year-old woman with biopsy-proven chronic hepatitis B, who had been treated
      with human leukocyte-derived interferon-alpha (huLe-IFN alpha) therapy for two
      months was found to have liver tumors on routine abdominal ultrasonography
      examination. She underwent laparotomy, and partial hepatectomy was performed
      under the clinical diagnosis of hepatocellular carcinoma. The lesions were
      diagnosed histologically as pseudolymphoma based on the massive infiltration of
      small mature lymphocytes and the presence of hyperplastic lymph follicles with
      germinal centers. Immunohistochemistry revealed polyclonal origin of the involved
      lymphocytes. The possible association between IFN alpha treatment and chronic
      hepatitis B with the development of pseudolymphoma is discussed.

PMID- 7514057
TI  - Landau-Kleffner syndrome: acquired epileptic aphasia in children.
AB  - Acquired epileptic aphasia, or Landau-Kleffner syndrome (LKS), once thought to be
      a rare syndrome, may occur more frequently in the pediatric population than once
      thought. This syndrome is typically characterized by an abrupt or gradual loss of
      language ability and inattentiveness to sound, sometimes called auditory agnosia,
      with onset during the first 5 years of life. This interruption in communication
      ability is generally closely preceded, accompanied, or followed by the onset of
      seizure activity and/or abnormal electro-encephalographic (EEG) findings. This
      report describes two cases of LKS evaluated at the same hearing and speech
      center. Because of the characteristic language regression and inattentiveness to
      sound, speech-language pathologists and audiologists are likely to be among the
      first professionals to evaluate these children. It is imperative that
      communication specialists be alert to the characteristic symptoms of LKS in order
      to be instrumental in initiating an appropriate diagnostic and management
      process. A multidisciplinary approach to identification and rehabilitation is
      encouraged in order to effectively re-establish communication skills for these
      children.

PMID- 7514060
TI  - Anatomy of the action potential in the heart.
AB  - The surface electrocardiogram can be simply described as the P, QRS, and T (and
      U) waves, together with PR and ST segments. However, it is actually the summation
      of the action potential from the sinoatrial node, the atria, the atrioventricular
      node, the His-Purkinje system, and the ventricles. Although the action potential
      can be divided grossly into 5 phases, its characteristics vary in different
      cardiac tissue. This is because the action potential is the end-result of
      multiple ion channels, pumps, and exchangers opening and closing in concert, and
      the properties and distribution of these components can be different from one
      tissue to another. The ion channels can be activated by changes in the membrane
      voltage and specific ligands, and can be modulated by factors such as
      neurotransmitters (e.g., through the G-protein system), the G-proteins directly,
      or other ions. Only in the last 10 years have investigators been able to use
      molecular biology techniques to peek into the primary structure of ion channels
      and to develop more workable models of the channel functions. The primary
      structure and the putative secondary structure of the ion channels show
      resemblance among the groups, suggesting that, except for IsK, the development of
      ion channels started with IK1 and IK(ACh), followed by Ito and IK, and then by
      INa and ICa. However, limitations still exist in our knowledge of the ion
      channels and hence of the action potential. This is demonstrated by the lack of
      effective pharmacologic treatment of cardiac arrhythmias to this date. It is to
      be hoped that advances in cell electrophysiology, genetic engineering, and
      molecular imaging techniques will soon end the dark days of antiarrhythmic
      therapy.

PMID- 7514059
TI  - A higher plant extracellular vitronectin-like adhesion protein is related to the
      translational elongation factor-1 alpha.
AB  - Higher plant proteins immunologically related to the animal substrate adhesion
      molecule vitronectin have recently been observed and implicated in a variety of
      biological processes, such as plasma membrane-cell wall adhesion, pollen tube
      extension, and bacterium-plant interaction. We provide evidence that, similar to
      vitronectin, one of these proteins, PVN1 (plant vitronectin-like 1), isolated
      from 428 mM NaCl-adapted tobacco cells binds to glass surfaces an heparin. PVN1
      was isolated by glass bead affinity chromatography. Isolated PVN1 has adhesive
      activity based on results from a baby hamster kidney cell-spreading assay. This
      plant adhesion protein was detected in all tissues examined but was most abundant
      in roots and salt-adapted cultured cells. Immunogold labeling indicated that PVN1
      is localized in the cell wall of cortical and transmitting tissue cells of
      pollinated mature styles. A partial amino acid sequence of PVN1 revealed no
      similarity with vitronectin but, instead, was nearly identical to the
      translational elongation factor-1 alpha (EF-1 alpha). A clone isolated by
      screening a tobacco cDNA expression library with anti-PVN1 encoded a protein with
      greater than 93% identity to sequences of EF-1 alpha from plants of numerous
      species. Immunological cross-reactivity between tobacco PVN1 and EF-1 alpha as
      well as the reaction between the EF-1 alpha antibody and the 65- and 75-kD
      vitronectin-like proteins of a fucoidal alga supported the conclusion that the
      plant extracellular adhesion protein PVN1 is related to EF-1 alpha.

PMID- 7514061
TI  - Neointima formation after acute vascular injury. Role of counteradhesive
      extracellular matrix proteins.
AB  - Restenosis currently limits the long-term beneficial effects of balloon coronary
      angioplasty. Two important cellular events in the development of clinically
      significant luminal narrowing after angioplasty are 1) increased production of
      extracellular matrix proteins and 2) acquisition of a motile phenotype by
      vascular smooth muscle cells. In this paper, smooth muscle cell responses that
      produce a fibrocellular neointima after acute vascular injury are reviewed.
      Particular emphasis is placed on specialized extracellular matrix proteins
      implicated in cell movement and tissue repair. Tenascin and thrombospondin are
      large, modular extracellular matrix glycoproteins; they possess both adhesive and
      counteradhesive domains and are expressed at high levels during smooth muscle
      cell migration and neointima formation after balloon injury to rat carotid
      artery. The ability of both tenascin and thrombospondin to down-regulate the
      assembly and activity of focal adhesions (points of cell-extracellular matrix
      adhesive interactions) may be important in the conversion of stationary,
      quiescent smooth muscle cells to cells that are able to move and divide within
      the strongly adhesive vessel wall. Moreover, tenascin is present in the
      extracellular matrix as a large 6-armed oligomer (a hexabrachion) that contains
      both cell-binding and matrix protein-binding domains in each of the hexabrachion
      arms. The large size and multidomain structure of tenascin and thrombospondin
      suggest that these proteins may be particularly well suited to form a nascent
      provisional matrix at sites of 1) neointima formation after acute vascular
      injury, 2) new growth and expansion within primary atherosclerotic plaques, and
      3) intimal repair and luminal narrowing in restenosis after angioplasty.

PMID- 7514063
TI  - Distribution of C3-step regulatory proteins of the complement system, CD35 (CR1),
      CD46 (MCP), and CD55 (DAF), in hematological malignancies.
AB  - The distribution and levels of three membrane proteins, CD35, CD46, and CD55,
      which serve as complement regulators, were examined in normal peripheral blood
      and hematologically malignant cells. CD35 was negative in most leukemia cells
      regardless of the type of leukemia, although granulocytes, monocytes, and some
      populations of lymphocytes were CD35+. CD46 was present in all blood cells except
      erythrocytes, and levels were 2-8 times higher in most leukemia cells than in
      their mature counterparts, particularly in CML and CLL cells, except for those of
      B cell lineage. CD55, a widely-distributed phosphatidyl inositol-anchored
      protein, was more frequently lost in NHL cells than in other types of
      hematological malignancies. In this review, we discuss the roles, mechanisms, and
      clinical applications of cell-associated complement regulatory proteins in
      hematological malignancies.

PMID- 7514064
TI  - Alternate splicing creates two forms of the human kit protein.
AB  - The Kit gene encodes for a transmembrane tyrosine kinase receptor that is
      expressed during early hematopoiesis and in a large proportion of blast cells of
      patients with acute myeloblastic leukemia (AML). Tissue culture studies have
      revealed that the growth factor recognized by the Kit protein is a stimulator of
      both colony formation and self renewal of AML cells. During an analysis of the
      Kit gene in AML cells we identified two different RNA transcripts differing by 12
      nucleotides just 5' of the transmembrane encoding region. Analysis of a variety
      of tissues revealed that both forms of RNA are expressed in all of the tissues
      that produce Kit. Sequencing of the corresponding genomic region revealed that
      the two forms of RNA arose through the alternate use of 5' splice donor sites.

PMID- 7514065
TI  - TGF beta 1 and IL-4 have opposing effects on the proliferation of chronic phase
      chronic myeloid leukaemic cells stimulated by G-CSF in vitro.
AB  - The effects of transforming growth factor beta 1 (TGF beta 1) have been studied
      in vitro on the clonogenicity of haemopoietic progenitor cells (CFU-CML) from 14
      patients with chronic myeloid leukaemia (CML) in chronic phase and 13 normal
      donors. In 14/14 patients with CML, 5 ng of TGF beta 1/dish decreased CFU-CML
      formation in cultures stimulated with 15 ng of granulocyte colony-stimulating
      factor (G-CSF)/dish (p < 0.0005) and in 13/14 patients TGF beta 1 reduced CFU-CML
      formation induced by G-CSF in combination with 5 ng of recombinant human
      interleukin-4 (rhIL-4)/dish (p < 0.005). In 10/14 samples the number of CFU-CML
      were reduced to levels lower than in cultures containing G-CSF alone (p < 0.01).
      In contrast, TGF beta 1 had no significant inhibitory effect on the G-CSF
      directed proliferation of normal donor mononuclear cells (MNC) either alone or in
      combination with rhIL-4. RhIL-4 increased G-CSF-induced colony formation in 13/14
      CML samples (p < 0.001), but did not have the same effect in the normal donor
      samples. The in vitro clonogenicity of CML peripheral blood MNC stimulated with
      15 ng of G-CSF could not be correlated with the white cell count or the
      percentage of CD34+ cells at diagnosis.

PMID- 7514062
TI  - Prognostic value of PCNA and cytokeratins for radiation therapy of oral squamous
      cell carcinoma.
AB  - In a retrospective pilot study we compared morphologically the first biopsies of
      20 patients suffering from oral squamous cell carcinoma (OSCC) where
      preoperatively performed radiation therapy [gamma rays (cobalt-60)] was
      successful with 20 patients who underwent the same therapy without the expected
      success. All specimens were formalin fixed and paraffin embedded. We performed
      haematoxylin and eosin staining and immunohistochemistry (ABC-method) applying
      broad spectrum cytokeratin, cytokeratin (CK) 1 + 2, 3 + 6, 13 and anti
      proliferating cell nuclear antigen (PCNA, PC10). The specimens of the patients
      with success of the radiotherapy showed statistically higher levels of PCNA
      positive tumour cells, measured by a computerised morphometric analysis system
      (VIDAS). These specimens showed significantly less CK 3-6 positive tumour cells
      than the specimens of the patients with failure of this therapy. The difference
      in the content of proliferating cell nuclear antigen might explain the different
      results of the performed radiation therapy. The difference in cytokeratin 3 + 6
      expression might be linked with the different amount of benign
      hyperproliferation. Prospective studies are planned to prove the results.

PMID- 7514066
TI  - Reversed-phase high-performance liquid chromatography assay for recombinant
      acidic fibroblast growth factor in E. coli cell suspensions and lysate samples.
AB  - A reversed-phase HPLC assay for acidic Fibroblast Growth Factor (aFGF) expressed
      in E. coli is described. The assay was developed on a Polymer Labs. PLRP-S
      macroporous poly(styrene-benzene) column. A sample preparation procedure was
      developed to permit quantitation of aFGF in crude samples, such as cell
      suspensions and cell lysates. The assay was linear over the range of 25-140
      micrograms/ml with an accuracy of 5%. By using a POROS column containing a
      stationary phase with "through-pores" and a superficial mobile phase velocity of
      1440 cm/h, the analysis could be performed in 3 min. The polymeric supports used
      for this assay were durable; periodic washing with sodium hydroxide maintained
      column performance for extended periods.

PMID- 7514067
TI  - Some basic guidelines in the use of chemotherapy for patients with incurable
      malignancy.
AB  - The increasing use of cytotoxic chemotherapy for patients with incurable
      malignancy has raised a number of practical and ethical dilemmas for health care
      workers in the fields of oncology and palliative medicine. This paper addresses
      some of these issues and attempts to suggest basic principles which may
      contribute to the successful use of palliative chemotherapy.

PMID- 7514068
TI  - Palliative care services in Britain and Ireland--update 1991.
AB  - The objective of this study was to repeat part of a survey carried out the
      previous year and to describe and quantify the hospice and palliative care
      inpatient units throughout Great Britain and Ireland for the year 1991, this also
      to include a survey of palliative care day centres and hospital support services.
      Questionnaires were sent to 346 hospice and palliative care services in Great
      Britain and Ireland. Replies were analysed by the Hospice Information Service. A
      total of 293 replies were received (84% response). The report details bed usage,
      length of stay and admissions, deaths and discharges in inpatients units. It also
      describes provision of day centre places and types of services offered. An
      initial assessment is made of the different types of hospital palliative care
      support services available. An estimate of the number of patients receiving
      palliative care in inpatient units and in day care centres is made.

PMID- 7514069
TI  - A self-evaluated assessment suitable for seriously ill hospice patients.
AB  - Current quality of life (QOL) assessments, whilst being suitable for patients
      undergoing active treatment, are often too cumbersome for patients who are in the
      terminal phase of their illness, and may themselves produce distress. In an
      attempt to measure QOL in these patients a simple assessment was piloted (PEPS-
      patient evaluated problem score) in which patients were asked to identify and
      grade major problems as they perceived them and also to grade problems previously
      identified by the medical and nursing staff. A global QOL score and a self
      administered WHO score completed the assessment. Of 70 patients admitted to the
      unit over a seven-month period, 44 completed questionnaires, 38 in full.
      Subsequently, uptake has been far greater (due to establishment of the method as
      part of routine care) with 73% of all patients admitted to our unit completing
      PEPS. Overall, a mean of 5.6 problems per patient were identified, of which 14%
      were psychosocial. Of those patients who completed questionnaires, 58% identified
      problems not picked up by the nursing and medical staff; 52% of these were
      psychosocial problems. Of 28 patients who died having previously completed
      questionnaires 22 had done so in the previous three weeks including eight in the
      previous seven days. PEPS has proved very useful in the management of patients,
      enabling the identification of previously unrecognized or underrated problems,
      particularly of a psychosocial nature, and also as a means of evaluating
      progress. It is readily acceptable to patients, even those close to death.

PMID- 7514071
TI  - An audit of morphine prescribing in a specialist cancer hospital.
AB  - The object of this study was to assess the quantity and quality of morphine
      prescribing in a specialist cancer hospital. An audit of prescription charts of
      all patients was performed using palliative care unit recommendations as the
      standard. The major weaknesses identified in morphine prescription were a lack of
      provision of breakthrough doses, the use of 'as required' (prn) oral morphine in
      the absence of regular oral morphine, and the lack of reference in the unit
      guidelines to co-prescription of aperients, antiemetics and night sedation. These
      deficiencies were targeted in an education programme and the survey was repeated
      to complete the audit cycle. Although some improvement in prescribing practice
      was shown, persistent problems have illustrated the need for an ongoing hospital
      wide education programme.

PMID- 7514072
TI  - The closure of an abdominal fistula using self-polymerizing silicone rubbers-
      case study.
AB  - A case is described where an abdominal fistula was temporarily closed using a
      plug made from dental addition curing silicone rubber impression material. An
      effective seal was maintained using a stoma flange and a gentle pressure
      dressing; this still allowed normal gastric function.

PMID- 7514073
TI  - Experience with dipipanone elixir in the management of cancer related pain--case
      study.
AB  - The synthetic opioid dipipanone is infrequently used in the UK in the management
      of malignant pain, principally because of the inflexibility of the Diconal
      combination preparation (dipipanone 10 mg with cyclizine 30 mg). We present three
      patients in which dipipanone elixir proved to be their own drug of choice in the
      management of opioid responsive cancer pain, and our experience with 15 other
      patients. Dipipanone elixir was formulated 10 mg/5 ml, in single strength
      chloroform water.

PMID- 7514070
TI  - Safety and efficacy of nebulized lignocaine in patients with cancer and
      breathlessness.
AB  - Although anecdotal reports suggest nebulized lignocaine may help breathlessness
      in patients with cancer this has not been examined formally. We report a pilot
      study comparing nebulized lignocaine 100 mg and 200 mg with saline in six
      patients with cancer who were breathless at rest. Nebulized lignocaine was well
      tolerated apart from mild bronchoconstriction in two patients after the 200 mg
      dose and the unpleasant taste; serum concentrations were below levels at which
      toxicity has been reported. The effort of breathing (measured on a visual
      analogue scale) did not differ between treatments, whereas the distress of
      breathing was less after saline than after either dose of lignocaine. These
      findings do not support the reported benefits of nebulized lignocaine.

PMID- 7514074
TI  - Resuscitation and non-resuscitation orders.

PMID- 7514075
TI  - Coronary endothelial function in cardiac transplant recipients with accelerated
      coronary disease.
AB  - BACKGROUND: Previous studies with the endothelium-dependent vasodilator substance
      P have shown a preserved vasodilator response in cardiac transplant recipients
      with angiographically normal coronary arteries. Although endothelial dysfunction
      is known to occur in cardiac transplant recipients with accelerated coronary
      disease, the degree to which the endothelium is affected is not known precisely.
      The aim of the present study was to examine endothelial function in accelerated
      coronary disease following cardiac transplantation. METHODS: Thirteen cardiac
      transplant recipients with epicardial coronary disease underwent substance P
      infusion. The response to incremental doses of substance P was measured in smooth
      segments of affected coronary arteries. Substance P was infused over 2 min with a
      starting dose of 1.4 pmol/min and a maximum of 22.4 pmol/min, reached by doubling
      the dose in steps, followed by an infusion of 2 mg isosorbide dinitrate over 2
      min. RESULTS: Substance P caused less vasodilation at lower concentrations, with
      a significantly higher dose required to achieve half maximal dilation compared
      with cardiac transplant recipients with no coronary disease. The mean maximal
      dilatation achieved with substance P was 22.98 +/- 4.62% compared to 21.95 +/-
      4.9% with isosorbide dinitrate; the latter value was not significantly different
      from the maximal dilation achieved in cardiac transplant recipients without
      coronary disease. CONCLUSIONS: In cardiac transplant recipients with accelerated
      coronary disease the functional vasodilatory ability of the coronary endothelium
      is impaired in segments of apparently unaffected epicardial arteries, which may
      lead to an increase in the resting vasoconstrictor tone and have important
      functional and therapeutic implications.

PMID- 7514076
TI  - "Rendez-vous" procedure (RVP) for obstructive jaundice.
AB  - Seven patients with obstructive jaundice were palliatively treated with the
      "rendez-vous" procedure, which combines a percutaneous and an endoscopic approach
      to stent insertion into the biliary system. In six cases, pretreatment
      papillotomy was not needed. Endoscopy was also not really necessary for stenting
      in one patient. This procedure should be restricted for use in cases of
      endoscopic failure.

PMID- 7514077
TI  - Preferential localization of c-kit product in tissue mast cells, basal cells of
      skin, epithelial cells of breast, small cell lung carcinoma and
      seminoma/dysgerminoma in human: immunohistochemical study on formalin-fixed,
      paraffin-embedded tissues.
AB  - Eighteen hundred and eighty-four cases of human solid tumours and 833 samples of
      normal human tissues, formalin-fixed and paraffin-embedded, were examined
      immunohistochemically for expression of c-kit oncogene product using polyclonal
      antibody against synthesized c-kit peptide. Seminoma/dysgerminoma and small cell
      lung carcinoma (SCLC) show preferential c-kit expression at 92% and 36%
      frequency, respectively, whereas only sporadic cases of cervical carcinoma and
      non-SCLC lung carcinoma show c-kit positivity. A normal tissue counterpart
      positive for c-kit product is detected in the testis (spermatocyte) and ovary
      (oocyte) but not in the lung or the cervix. In contrast, normal epithelial cells
      of the breast, skin basal cells and tissue mast cells harbour c-kit product, but
      transformed cells of the former two are largely deficient in the c-kit protein.
      One hundred and thirty-nine neuroendocrine tumours and 39 non-pulmonary small
      cell carcinomas were all negative, except for two cases of neuroblastoma. This
      indicates a distinct character for SCLC in c-kit expression. The c-kit product
      may be a useful marker in diagnostic pathology of seminoma/dysgerminoma and SCLC
      among human solid tumours, and in distinction of SCLC from non-pulmonary small
      cell carcinoma.

PMID- 7514078
TI  - PMA-activation of peripheral blood and tonsillar B lymphocytes induces large
      adhesive cells reminiscent of large extrafollicular (monocytoid) B cells.
AB  - Extrafollicular (EF) B lymphocytes differ in size and morphology depending on the
      lymphatic organ involved and the kind of inflammatory reaction. On re-evaluating
      EF B cells in various sites and conditions we discriminated three forms: a small
      (lymphoid) and intermediate (centrocytoid), and a large (monocytoid) variant.
      Immunohistochemically, these variants could be discriminated by their
      differential expression of adhesion molecules CD62L (L-selectin) and CD11c: small
      EF B cells were strongly L-selectin+ and CD11c-; intermediate cells were
      moderately CD62L+ and CD11c-; large cells were faintly CD62L+ or - but expressed
      CD11c. In 72 h cultures of normal peripheral and tonsillar B cells, cross-linking
      surface immunoglobulin in the presence of interleukin-2 or interleukin-4 led to
      formation of clusters in vitro together with an increase in cell size and a
      slight up-regulation of CD11c, as determined by flow cytometry. Stimulation with
      phorbol 12-myristate 13-acetate (PMA), however, gave rise to large, plastic
      adherent cells which also showed strong homotypic adhesion, expressed CD62L at
      minimal levels and CD11c at comparably highest levels and altogether mimicked the
      large cell variant of EF B cells. We conclude that EF B cells are subjected to
      cytokine-induced metamorphosis and that differences in cell size and morphology
      reflect their state of activation and activation-associated adhesion properties.
      Our data suggest that EF B cells in all anatomical sites are functionally closely
      related cells which--possibly mediated by CD11c/CD18--may become sessile and
      proliferate locally once activated by appropriate signals.

PMID- 7514079
TI  - Epidermoid cyst of the spleen: a cytokeratin profile with comparison to other
      squamous epithelia.
AB  - The stratified squamous epithelium of a splenic epidermoid cyst was studied with
      a battery of monoclonal antibodies to cytokeratin (CK) proteins. CKs 10 and 11
      were found in the suprabasal layers of the stratified squamous epithelium, while
      staining for CK 13 was focal or diffuse throughout. CKs 18 and 19 decorated
      individual squamous cells or stained the entire thickness of the epithelium.
      These results were compared with those previously obtained by us in stratified
      squamous epithelia of ovarian mature cystic teratoma, fetal epidermis, adult
      epidermis and squamous metaplasia in a peritoneal cyst. From these comparisons it
      emerges that the epidermoid splenic cyst is either of teratomatous derivation or
      originates from inclusion of fetal squamous epithelium. Squamous metaplasia of
      mesothelium or inclusions of mature squamous epithelium appears to be an unlikely
      source of origin of these cysts.

PMID- 7514081
TI  - Methylprednisolone and membrane properties of primary cultures of mouse spinal
      cord.
AB  - The present study attempts to define the capacity of methylprednisolone sodium
      succinate (MP) to protect neuronal membranes against a free radical challenge in
      primary cultures of fetal mouse spinal cord. Incubation of these cultures with MP
      significantly increased the Na+,K(+)-ATPase activity, an effect that was blocked
      by the RNA synthesis inhibitor, actinomysin D and the protein synthesis
      inhibitor, cycloheximide, suggesting an induction of protein synthesis by MP. In
      contrast, incubation with FeCl2 for 1 or 2 h significantly inhibited Na+,K(+)
      ATPase activity and elevated the levels of thiobarbituric acid-reactive
      substances (TBARS). Pretreatment with MP prevented the rise in TBARS and
      partially prevented the decrease in Na+,K(+)-ATPase activity for the first hour
      of FeCl2 incubation, an effect that was lost during the second hour. A second
      dose of MP after the first hour of incubation with FeCl2 partially restored
      Na+,K(+)-ATPase activity and reduced TBARS levels after the second hour of
      exposure to FeCl2. Co-incubation of MP with cycloheximide completely prevented
      the decrease in Na+,K(+)-ATPase activity seen after a 2-h incubation with FeCl2
      and eliminated the need for a second dose of MP after the first hour of
      incubation with FeCl2. These findings suggest a capacity for rapid protein
      induction and antioxidant activity for MP in vitro.

PMID- 7514080
TI  - Sarcoma of the pulmonary artery: report of four cases with electron microscopic
      and immunohistochemical examinations, and review of the literature.
AB  - Herein we report the clinicopathological features of four cases of pulmonary
      artery sarcoma that appeared at our institution during a period of 30 years. The
      patients, 2 males and 2 females, were 50-62 years old. Tumour was found in the
      pulmonary trunk and right pulmonary artery in all cases, in the pulmonary valve
      and left pulmonary artery in three of the four cases, and in the right
      ventricular outflow tract in one case. There was direct extension or metastases
      to the lungs in two cases, the heart in one case, mediastinum or lymph nodes in
      two cases and the pleura in one case. Ultrastructural examination in one case
      revealed cells with features of smooth muscle cells and myofibroblasts.
      Immunohistochemical examination of three cases gave the following results:
      vimentin and smooth muscle specific actin was positive in all three cases, desmin
      in one case and cytokeratin in one case. No positivity was found for Factor VIII.
      This and other studies indicate that histologically most pulmonary artery
      sarcomas are leiomyosarcomas or "undifferentiated spindle cell sarcomas".
      Immunohistochemical and ultrastructural examinations favour an origin from
      myofibroblasts, probably derived from multipotent (undifferentiated) cells in the
      wall of the vessel. Most lesions show extensive intrathoracic growth although
      they rarely metastasize outside the thoracic cavity. They have a poor prognosis
      although some cases are currently being diagnosed during life.

PMID- 7514082
TI  - NMDA causes release of nitric oxide from rat spinal cord in vitro.
AB  - Anatomic studies have localized nitric oxide synthase (NOS) activity in the rat
      spinal cord dorsal horn and intermediolateral cell column. Behavioral and
      electrophysiologic studies suggest that N-methyl-D-aspartate (NMDA) stimulates
      nitric oxide synthesis in the dorsal horn. This report describes a novel bioassay
      to determine directly in vitro whether NMDA causes release of nitric oxide from
      rat spinal cord. Modified Krebs-Henseleit solution at 26 degrees C was perfused
      over spinal cord slices from adult male rats, then dropped onto a ring of
      endothelium-denuded rat aorta. Following preconstriction with phenylephrine, NMDA
      (10(-10) to 10(-3) M) alone or with other drugs was added to the perfusion
      solution and vascular tension measured. NMDA-containing solutions applied
      directly on the preconstricted vessels without exposure to spinal cord tissue had
      no effect on vessel tone. In contrast, NMDA via the spinal cord perfusion caused
      concentration-dependent vascular relaxation, which was blocked by MK-801,
      hemoglobin, methylene blue, and several arginine analogues which inhibit NOS.
      [14C]citrulline assay suggested NOS in rat spinal cord was non-endothelial in
      nature. NMDA perfusion of spinal cord slices in vitro causes vascular relaxation
      in this bioassay due to actions on NMDA receptors and which is consistent with
      release of nitric oxide. These results support previous anatomical, behavioral,
      and electrophysiologic studies in rat spinal cord and describe a novel,
      sensitive, and simple bioassay for nitric oxide release from neural tissue in
      vitro.

PMID- 7514083
TI  - N-methyl-D-aspartate (NMDA) receptors in the spinal cord and motor cortex in
      motor neuron disease: a quantitative autoradiographic study using [3H]MK-801.
AB  - The distribution and density of NMDA receptors in spinal cord and motor cortex
      was compared in motor neuron disease (MND; 10 cases) and controls (8 cases) using
      [3H]MK-801 autoradiography. In the spinal ventral horn of MND cases, [3H]MK-801
      binding was reduced and there were fewer focal hot spots of binding. These
      changes are likely to reflect loss of motor neurons (MN) bearing NMDA receptors.
      [3H]MK-801 binding was increased in intermediate spinal grey matter and deeper
      layers of the motor cortex in MND cases compared to controls. This may represent
      either an adaptive response to MN loss or a pathophysiological phenomenon
      contributing to MN degeneration.

PMID- 7514084
TI  - The cortico-nigral projection in the rat: an anterograde tracing study with
      biotinylated dextran amine.
AB  - The projection from the cortex to the substantia nigra (SN) in the rat was
      studied using the biotinylated dextran amine (BDA) anterograde tracing method.
      Injections of BDA into the prefrontal cortex consistently yielded labeling of the
      thin nerve fibers with small boutons in the SN pars compacta (SNc) and the pars
      reticulata (SNr). The cortico-nigral projection had a loose medio-lateral and
      rostro-caudal arrangement. Injections of BDA into the precentral lateral, the
      parietal, the temporal, and the occipital cortices resulted in sparse or no
      labeling of boutons in the SN. The density of boutons in the most heavily labeled
      region of the SN was 0.23/10(3) micron3. For comparison, similar measurement was
      performed in the cortico-striatal projection. The density of the boutons in the
      the neostriatum was 4.9/10(3) micron3. This study indicates that the entire
      prefrontal cortex projects to the SNc and SNr and that the terminal density of
      this projection is much less than the cortico-striatal projection.

PMID- 7514085
TI  - Trolox attenuates cortical neuronal injury induced by iron, ultraviolet light,
      glucose deprivation, or AMPA.
AB  - The vitamin E analog, trolox, protected cultured cortical neurons against damage
      induced by exposure to either iron ions or ultraviolet (UV) light, consistent
      with an ability to inhibit free radical-mediated cytotoxicity. Trolox also
      reduced neuronal death induced by 24 h exposure to alpha-amino-3-hydroxy-5-methyl
      4-isoxazole propionic acid (AMPA), but not that induced by N-methyl-D-aspartate
      (NMDA). When combined with the NMDA receptor antagonist dextrorphan, trolox also
      reduced the neuronal injury induced by glucose deprivation.

PMID- 7514087
TI  - Congenital orbital teratoma: a clinicopathological case report including
      immunohistochemical staining.

PMID- 7514088
TI  - Circadian rhythm of glycogen in the hamster diaphragm.
AB  - The purpose of this study was to determine the diurnal fluctuation of glycogen
      stores for the whole hemidiaphragm and within a specific myofibrillar ATPase (M
      ATPase) fibre type and diaphragmatic region. Fifty-six golden Syrian hamsters
      were randomly divided into six groups according to the time of sampling biopsies
      from the diaphragm: 03:00, 07:00, 11:00, 15:00, 19:00, and 23:00. The right
      hemidiaphragm was quick frozen and biochemically assayed for glycogen levels.
      Biopsies from the left hemidiaphragm of the same animal were cut from the
      anterior costal and crural regions, and stained with periodic acid--Schiff (PAS)
      and for M-ATPase. Optical density measures of PAS-stained fibres were determined
      to quantitate glycogen in different M-ATPase fibre types and diaphragmatic
      regions. Biochemical assay of the entire hemidiaphragm showed slightly greater
      glycogen content of biopsies taken at 11:00 and 15:00 than at 03:00, 19:00, and
      23:00 (range of differences: 6.4-10.0%). However, glycogen levels within a
      specific M-ATPase fibre type and diaphragm region were not different in biopsies
      sampled at different times. Because the hamster has a small diurnal variation of
      glycogen in the diaphragm, which is similar to the small diurnal variation of
      glycogen in human skeletal muscle, this species may be a good animal model for
      metabolic studies of the diaphragm that could be affected by diurnal glycogen
      variability.

PMID- 7514086
TI  - Expression of the receptor for macrophage colony stimulating factor by brain
      microglia and its upregulation in brains of patients with Alzheimer's disease and
      amyotrophic lateral sclerosis.
AB  - The receptor for macrophage colony stimulating factor (CSF-1) was localized
      immunohistochemically in postmortem human brain tissue. Microglia constitutively
      expressed the receptor for CSF-1 and its expression was upregulated in lesions of
      Alzheimer's disease and amyotrophic lateral sclerosis. The CSF-1 mediated pathway
      appears to be involved in the response and activation of microglia in the central
      nervous system lesions.

PMID- 7514089
TI  - Prostate inhibin peptide (PIP) in prostate cancer: a comparative
      immunohistochemical study with prostate-specific antigen (PSA) and prostatic acid
      phosphatase (PAP).
AB  - Prostate inhibin peptide (PIP) is a polypeptide synthesized by the prostate gland
      that is involved in prostatic growth and differentiation. The objective of this
      study was to evaluate PIP as an immunocytochemical marker for prostatic
      adenocarcinoma (PCA) by comparing it with PSA and PAP. A total of 71 cases of
      primary PCA and 5 cases of metastatic PCA were studied. Primary tumors were
      specially selected to include a disproportionate number of high-grade tumors. The
      distribution of cases by Gleason score was 2-5, 14 cases; 6-7, 24 cases; and 8
      10, 33 cases. Four metastases were to bone (decalcified tissue) and one to soft
      tissue. All 71 cases of primary PCA stained positively for the three antibodies
      tested, with none demonstrating obvious superiority, although individual case
      variability was seen. In one bone metastasis, staining for PSA was negative, with
      both PAP and PIP giving positive results. All non-prostatic carcinomas tested
      were negative. These results indicate that PIP is as sensitive and specific an
      immunohistochemical marker as PSA and PAP in untreated prostate adenocarcinomas.
      Further, the androgen-independent nature of PIP may give it an advantage over
      PSA/PAP in tumors exposed to androgen ablating agents.

PMID- 7514090
TI  - Induction of cytogenetic adaptive response of mouse bone marrow cells to
      radiation by therapeutic doses of bleomycin sulfate and actinomycin D as assayed
      by the micronucleus test.
AB  - An in vivo micronucleus assay using bone marrow cells of Syrian albino male mice
      for identifying the possibility of induction of adaptive response to various
      doses of radiation following treatment with chemotherapeutics is described.
      Single doses of bleomycin sulfate (BLM-S) at 300 micrograms/kg and actinomycin-D
      (ACT-D) at 10 micrograms/kg body weight (therapeutic dose range) were injected
      intravenously 3 h prior to whole body gamma-irradiation. Irradiation at various
      doses from 1-4 Gy was carried out at a dose rate of 45 cGy/min. Animals were
      killed at 24, 36 and 48 h post-irradiation. The results obtained in this study
      clearly indicate a significant difference for radiation induced micronuclei (MN)
      in polychromatic erythrocytes (PCEs) with P value < 0.001 over the dose range
      used. When used in combination with radiation, neither ACT-D nor BLM-S caused a
      synergistic or additive effect. Irradiated animals showed a higher incidence of
      micronuclei formation in the presence of ACT-D and BLM-S. However, in both cases,
      the number of MN induced in PCEs was less than the sum of MN induced by radiation
      and ACT-D or BLM-S alone. The effect of combined treatment was reduced by a
      factor of 1.5 for BLM-S and greater than 1.5 for ACT-D treated animals. These
      observations indicate that although a small amount of ACT-D or BLM-S reaches the
      bone marrow cells via the circulation, these drugs might produce effects which
      make bone marrow cells resistant to the clastogenic effects of radiation.
      Therefore, using these agents repeatedly for cancer treatment in combination with
      radiation might not cause severe adverse biological effects in normal hemopoeitic
      tissue.

PMID- 7514091
TI  - Studies on the biological characterization and mitogenic interactions between
      hepatic stimulator substance and acidic fibroblast growth factor.
AB  - During liver regeneration, hepatic stimulator substance (HSS) and acidic
      fibroblast growth factor (FGF-1) are produced in the liver. These growth factors
      may be involved in liver growth control but an understanding of their regulatory
      interactions is limited. To further characterize the mitogenic activity of HSS,
      we compared its effects with FGF-1 in cells of hepatocyte, non-parenchymal liver
      epithelial and non-hepatic lineages. Our studies with these cell types
      demonstrated differences in the mitogenic specificities of HSS and FGF-1. Whereas
      exposure of primary hepatocytes to epidermal growth factor and HSS
      synergistically increased DNA synthesis, simultaneous exposure to HSS and FGF-1
      resulted in no such effect. Receptor-binding assays showed that HSS did not
      compete with FGF-1 in binding to FGF-1 receptors on rat primary hepatocytes.
      Additional immunoblot analysis demonstrated no cross-reactivity between FGF-1
      antibodies and HSS. Distinct mitogenic and immunologic properties of HSS and FGF
      1 should facilitate further analysis of liver regeneration and hepatic
      oncogenesis.

PMID- 7514092
TI  - A comparison of the effects of sodium saccharin in NBR rats and in intact and
      castrated male F344 rats.
AB  - High doses of sodium saccharin (NaSac) increase proliferation in the bladder of
      the rat, with a male preponderance. The possibility that alpha 2u-globulin is
      involved in its mechanism of action was evaluated by feeding it at 7.5% of the
      diet to NCI-Black-Reiter (NBR) male rats, which do not synthesize liver-derived
      alpha 2u-globulin. NaSac affected urinary parameters similarly in F344 and NBR
      male rats, but NBR rats consumed more water leading to greater urinary volume.
      NaSac produced less proliferation in NBR than in intact F344 rats, with
      intermediate changes in castrated F344 males, which had intermediate urinary
      alpha 2u-globulin levels.

PMID- 7514093
TI  - The shining stranger: application of the phenomenological method in the
      investigation of the nurse--family spiritual relationship.
AB  - Although many nurses and families may develop a spiritual relationship, a review
      of the literature showed few studies and scant literature addressing this topic.
      Furthermore, no studies were identified that used methodologies that provide
      descriptions and understanding of the meaning of this phenomenon. This article
      describes the application of the phenomenological method in the investigation of
      the meaning of a spiritual relationship between families and their nurses in a
      hospice setting. The phenomenological method can be used to uncover the meaning
      of experience through respondents' descriptions. Transcripts of interviews in
      which 11 nurses and 12 families were asked to describe their hospice experience
      were analyzed using Giorgi's approach to Husserlian phenomenology. Descriptions
      of nurse-family relationships were identified and synthesized into five thematic
      structures of experience: nurses' ways of being; nurses' ways of doing; nurses'
      ways of knowing; ways of receiving and giving; and ways of welcoming a stranger.
      The thematic structures of experience were synthesized into and interpreted as a
      metaunity of meaning. Through reflection, the unity of meaning was intuited as
      "The Shining Stranger." Analysis of selected Eastern and Western religious
      literature provided exemplars and a characterization of the shining stranger.
      Implications of the application of the phenomenological method are discussed.

PMID- 7514094
TI  - Synthesis of pentasaccharide core structures corresponding to the genus-specific
      lipopolysaccharide epitope of Chlamydia.
AB  - The trisaccharides allyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)
      (2-->6)-O-2-aceta mid o-2-deoxy- beta-D-glucopyranosyl-(1-->6)-2-acetamido-2
      deoxy-alpha- and -beta-D-glucopyranoside (16a and 16b), the tetrasaccharides
      allyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->4)-O-(sodium 3
      deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->6)-O-2-aceta mid o-2-deoxy- beta
      D-glucopyranosyl-(1-->6)-2-acetamido-2-deoxy-alpha- and -beta-D-glucopyranoside
      (19a and 19b), and the pentasaccharides allyl O-(sodium 3-deoxy-alpha-D-manno-2
      octulopyranosylonate)-(2-->8)-O-(sodium 3-deoxy-alpha-D-manno-2
      octulopyranosylonate)-(2-->4)-O-(sodium 3-deoxy-alpha-D-manno-2
      octulopyranosylonate)-(2-->6)-O-2-aceta mid o-2-deoxy-bet a -D-glucopyranosyl-(1-
      >6)-2-acetamido-2-deoxy-alpha- and -beta-D-glucopyranoside (23a and 23b) were
      prepared. The glycosidic linkages were formed using 1,3,4,6-tetra-O-acetyl-2
      chloroacetamido-2-deoxy-beta-D-glucopy ran ose (6) and FeCl3 as promoter as well
      as per-O-acetylated Kdo mono- and di-saccharide bromide derivatives (12 and 20)
      under Helferich conditions. The oligosaccharides, which correspond to
      dephosphorylated part-structures of enterobacterial and chlamydial
      lipopolysaccharides, were characterized by NMR spectroscopy as well as plasma
      desorption and matrix-assisted laser desorption mass spectrometry.

PMID- 7514095
TI  - Structure of the O-specific polysaccharide of the O22-antigen (LPS) from
      Escherichia coli O22:K13.
AB  - The polysaccharide moiety of the O22-antigen (lipopolysaccharide, LPS) consists
      of 2-acetamido-2-deoxy-D-galactose, D-glucuronic acid, D-glucose, and D-galactose
      in the molar ratios 2:1:1:1. Methylation analysis as well as 1D and 2D NMR
      spectroscopy showed that the O22 polysaccharide has the primary structure
      [formula: see text]

PMID- 7514096
TI  - Structure of the O-specific side chain of the lipopolysaccharide from Escherichia
      coli O126.
AB  - The polysaccharide isolated from Escherichia coli O126 lipopolysaccharide
      contains D-galactose, D-mannose, L-fucose, and 2-acetamido-2-deoxy-D-glucose in
      the molar ratios 1:1:1:1. The structure of the O-antigen of the
      lipopolysaccharide from E. coli O126 was established by compositional analysis,
      partial degradation, methylation analysis, and nuclear magnetic resonance
      spectroscopy. These studies revealed that the O-antigen is branched and built up
      of tetrasaccharide repeating units having the following structure: [formula: see
      text]

PMID- 7514097
TI  - The sulphation pattern in chondroitin sulphate chains investigated by
      chondroitinase ABC and ACII digestion and reactivity with monoclonal antibodies.
AB  - We have used progressive chondroitinase digestion of pig aggrecan in conjunction
      with ELISA assays and disaccharide analysis to derive information about the
      pattern of 4- and 6-sulphation in chondroitin sulphate chains. Digestion with
      chondroitinase ABC resulted in the release of mainly disaccharides from the
      nonreducing terminal of chondroitin sulphate chains but there was also the
      release of some tetra- and hexa-saccharides which were degraded to disaccharides
      with more extensive digestion. Chondroitinase ACII, in contrast, released only
      disaccharides. Analysis of the disaccharide composition of the intact and
      digested products at different stages of digestion showed that there was a slight
      increase in 6-sulphate content of the chains as they were shortened. Reaction of
      the partially digested proteoglycans with monoclonal antibodies 3-B-3 and 3-D-5
      which recognise chains terminating in 6- or 4-sulphated disaccharides,
      respectively, showed major differences between chondroitinase ABC and ACII
      products. The results suggested that chondroitinase ABC preferentially cleaved
      next to 4-sulphated, rather than 6-sulphated disaccharides and this resulted in
      some oligosaccharides as well as disaccharide being released. Chondroitinase ACII
      also cleaved an additional disaccharide next to the linkage to protein of
      chondroitin sulphate, which was not removed by chondroitinase ABC and this
      disaccharide was mainly nonsulphated.

PMID- 7514098
TI  - Preliminary investigation into the purification, NMR analysis, and molecular
      modelling of chondroitin sulphate epitopes.
AB  - Electrophoretic methods are outlined for the rapid purification and analysis of
      chondroitin sulphate oligosaccharides on a milligram scale. Isomeric impurities
      however, exist within specific sized oligosaccharides. Detailed 1H and 13C NMR
      data for the chondroitin sulphate disaccharides delta 4HexA(1-3)GalNAc6SO3- and
      delta 4HexA(1-3)GalNAc4SO3- (prepared from shark chondroitin sulphate) are
      reported. Two-dimensional NMR methods have been employed in the assignment of
      spectra. Preliminary models of these disaccharides are proposed from molecular
      mechanics conformational searching and molecular dynamics procedures. This study
      provides 1H and 13C NMR reference data which will be useful in the investigation
      of larger chondroitin sulphate oligosaccharides, such as those prepared by the
      electrophoretic methods mentioned above.

PMID- 7514100
TI  - How to identify and quantify an underperfused zone.

PMID- 7514099
TI  - Neutrophil mediated damage to isolated myocytes after anoxia and reoxygenation.
AB  - OBJECTIVE: The aim was to assess the role of neutrophils in anoxia-reoxygenation
      induced, neutrophil mediated damage to cardiac myocytes. METHODS: Neonatal rat
      cardiac myocytes in primary monolayer cultures were exposed to a 2 h period of
      anoxia, and subsequently reoxygenated for 3 h. Neutrophils were added at the time
      of reoxygenation, and myocyte injury was determined by release of lactate
      dehydrogenase (LDH). RESULTS: Neutrophils produced a dose dependent increase in
      myocyte LDH release. This effect was not enhanced by coincubation with a
      neutrophil activator (formyl-Met-Leu-Phe), or interleukin 1 alpha (IL-1 alpha),
      although IL-1 alpha increased anoxic myocyte damage. Exposure to supernatants
      from anoxic, or anoxic-reoxygenated, myocytes increased LDH release from normoxic
      myocytes, and conditioning of these supernatants by neutrophils further increased
      their cytotoxic potential. The anoxia-reoxygenation induced, neutrophil mediated
      LDH release was attenuated by some oxygen radical scavengers (superoxide
      dismutase, histidine, and desferrioxamine), but not others (catalase). Marked
      decrease in LDH release was also observed after addition of L-arginine, the
      substrate for synthesis of nitric oxide, along with the neutrophils at the time
      of reoxygenation. In addition, neutrophil mediated myocyte injury was attenuated
      by protease inhibitors (Eglin C and alpha 2 macroglobulin), an anti-CD18
      monoclonal antibody, and the methylxanthine derivative pentoxifylline,
      respectively. CONCLUSIONS: The results indicate that neutrophils increase myocyte
      reoxygenation damage, and that reoxygenated cardiac myocytes release potent
      neutrophil stimulants and cytotoxic mediators. The anoxia-reoxygenation induced,
      neutrophil mediated myocyte damage is dependent on oxygen free radicals,
      proteases, and cellular adhesion, and stimulation of endogenous NO production may
      be protective in this model.

PMID- 7514101
TI  - Cyclosporin A and FK506 inhibit activation-induced cell death in the murine WEHI
      231 B cell line.
AB  - The WEHI-231 B lymphoma cell line expresses the phenotype of immature B cells.
      Cross-linking of surface IgM induces programmed cell death (PCD) with typical
      features of apoptosis demonstrated by the decrease of cell DNA content, chromatin
      condensation, and nuclear fragmentation. Activation of protein kinase C (PKC) by
      phorbol esters was reported to protect WEHI-231 cells against apoptosis induced
      by ligation of antigen receptors. It was therefore hypothesized that PCD could
      result from a defect in PKC response with an imbalance in the phosphoinositide
      pathway in favor of Ca2+ mobilization. In support of this hypothesis, we show
      here that apoptosis can be readily triggered by the calcium ionophore ionomycin.
      Furthermore, pretreatment of cells with cyclosporin A or FK506 which inhibit
      selectively the phosphoprotein calcineurin, a calcium-and calmodulin-dependent
      serine/threonine phosphatase, protects WEHI-231 cells against apoptosis induced
      by ionomycin or ligation of surface IgM. Unlike phorbol esters, cyclosporin A did
      not impair the rise of intracellular Ca2+ induced by cross-linking of antigen
      receptors. Altogether, the data indicate that the phosphorylation status of yet
      undefined key cellular substrates controls the cellular response to calcium
      dependent apoptotic signals in this B cell lymphoma.

PMID- 7514102
TI  - The secondary B cell lineage for phosphorylcholine is conserved in CBA/CaHN-xid/J
      mice.
AB  - In order to determine the mechanism of generation of immunological memory, we
      used the splenic focus assay to analyze primary and in vitro generated secondary
      phosphorylcholine (PC)-specific B cell precursors in CBA/CaHN-xid/J mice (CBA/N)
      expressing an X-linked immune defect (xid). A quantitative analysis of the
      kinetics of the appearance of these precursors over the time of the culture
      period was performed. The precursors were analyzed for TEPC15 idiotype expression
      and epitope specificity. We found that there was a significantly reduced total
      frequency of PC-specific precursors in CBA/N female and (CBA/CaHN-xid/J female x
      BALB/cRos male)F1 (NBF1) male mice (xid phenotype), relative to BALB/c and NBF1
      female mice (normal phenotype). Memory precursors representing a distinct lineage
      of B cells, however, were present at normal levels in CBA/N female and NBF1 male
      mice. These results help explain the reported characteristics of the serum
      antibody responses induced in these mice and also better our understanding of the
      mechanism of B cell memory generation.

PMID- 7514103
TI  - Deregulated expression of c-fos disturbs proliferative responses of B cells to
      sIg cross-linking.
AB  - B cell activation by surface immunoglobulin (sIg) cross-linking is accompanied by
      transient expression of the c-fos protooncogene. This expression is strictly
      controlled in the B cells. To investigate a biological implication of the c-fos
      expression in the process of B cell activation by sIg cross-linking, we examined
      the proliferation of splenic B cells from H2-c-fos transgenic mice. Constitutive
      expression of the c-fos gene perturbs de novo synthesis of RNA and DNA in the B
      cells stimulated with anti-IgM antibody. Early events of signal transduction such
      as an increase in intracellular free calcium level and an induction of the
      endogenous immediate early genes (c-fos and c-myc) were apparently intact in
      those B cells. When the sIg stimulation of B cells was mimicked by the
      costimulation with 12-O-tetradecanoylphorbol 13-acetate and ionomycin, H2-c-fos B
      cells required higher concentrations of ionomycin for the optimal proliferative
      responses, suggesting that calcium-dependent signal transduction pathways are
      disturbed in those B cells. These results demonstrate a novel regulatory effect
      of c-fos protein on the proliferation of B cells mediated by sIg cross-linking.

PMID- 7514104
TI  - A unique murine CD43 epitope Lp-3: distinct distribution from another CD43
      epitope S7.
AB  - In foregoing studies, we found a unique B cell differentiation antigen Lp-3 which
      is expressed on pre-B and premature B cells in the bone marrow, but is negative
      on bone marrow mature B cells and peripheral resting B cells. Nonetheless, Lp-3
      was clearly positive on the majority of CD5 B(B1) cells. When we examined the
      biochemical nature and partial amino acid sequences of purified 132-kDa Lp-3
      molecules and the nucleotide sequence of the cDNA clones, we found that Lp-3 is
      an epitope of CD43. Thus, the monoclonal antibody (mAb) Lp-3 may be the first mAb
      to murine CD43 defined by primary target structure analysis. Comparison of tissue
      distribution of Lp-3 and S7, an epitope previously suggested to associate with
      murine CD43, showed that they were similarly distributed on thymocytes,
      peripheral B and T cells, granulocytes, and platelets. In the bone marrow, while
      both Lp-3 and S7 were negative on mature B cells, the former was positive on all
      B lineage cells at an early ontogeny and the latter was positive only on the
      minor population of pre-B cells and pro-B cells. Lp-3 and S7 epitopes also showed
      different distributions on basement membranes of renal glomerulus, bronchus, and
      endometrium, lining cells of choroid plexus and muscular cells of arterioles in a
      variety of tissues. As CD43 has various isoforms generated by different degrees
      of glycosylation of the common core peptide, it is likely that Lp-3 and S7 are
      associated with different CD43 isoforms.

PMID- 7514105
TI  - Modulation of endothelial cell adhesion molecule expression in a situation of
      chronic inflammatory stimulation.
AB  - Different disorders affecting the respiratory tract are characterized by the
      development of a chronic inflammatory reaction with an accumulation of immune and
      inflammatory cells into the bronchial walls and in interstitial and alveolar
      spaces. By its ability to secrete a large panel of cytokines, in particular TNF
      alpha, the alveolar macrophage (AM) is undoubtedly playing a key role in the
      complex interactions between inflammatory and structural cells potentially
      implicated in the inflammatory reaction of the lung. One aspect of these
      interactions is the capacity of AM-derived TNF-alpha to induce the expression of
      cellular adhesion molecules (CAM) on the surface of endothelial cells. The main
      information concerning the induction of CAM have been obtained under experimental
      conditions mimicking an acute inflammatory reaction. In the present study, we
      propose an in vitro model allowing the reproduction of the conditions of a
      chronic inflammation, namely, the endothelial cell behavior submitted to a
      chronic TNF-alpha stimulation. The endothelial cell activation parameters were
      the modulation of expression of adhesion molecules: endothelial-leukocyte
      adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and
      vascular adhesion molecule-1 (VCAM-1). Their functional abilities was evaluated
      using U937 cell adhesion analysis. Results demonstrated an overexpression of ICAM
      1 after chronic stimulation performed with low but repeated doses of TNF-alpha.
      The level of ICAM-1 expression persisted throughout the culture to reach a high
      stable level despite the absence of detectable TNF-alpha activity in culture
      supernatants. If the stimulation was stopped after 6 days, the expression of ICAM
      1 was still observed at least until Day 15. E-selectin and VCAM-1 expression
      remained absent or not significantly increased. The expression of ICAM-1 on
      endothelial cells was directly related to an enhanced adhesion capacity as
      demonstrated by the adhesion of U937 cells to endothelial cells by an ICAM-1/LFA
      1 adhesion pathway. Taken together, these elements could bring new approaches in
      the investigation of mechanisms by which inflammatory cells are recruited and
      participate in chronic inflammatory processes.

PMID- 7514106
TI  - Expression of the zeta protein subunit in CD3- NK effectors derived from human
      thymus.
AB  - The origin, lineage derivation, and sites of human natural killer (NK) cell
      differentiation are presently unresolved. The vast majority of NK cells found in
      peripheral blood have surface membrane expression of CD2 and CD16. Both antigens
      trigger activation pathways which require the zeta protein, a signal-transducing
      subunit of the CD3-T cell receptor (CD3-TCR) complex which is found as an
      isolated homodimer (zeta-zeta) or heterodimer (zeta-Fc epsilon RI gamma) in human
      NK cells. Unlike NK cells found in adult peripheral blood, NK cells derived in
      vitro from human CD34+ hematopoietic progenitor cells lack CD2 and CD16, and
      those found in fetal liver constitutively express CD3 epsilon and delta proteins.
      However, NK effectors derived in vitro from immature human CD3- thymocytes show
      striking phenotypic and functional similarities to adult human NK cells. In this
      report, we characterize zeta protein expression in CD3- thymocytes following
      short-term culture in recombinant (r)IL-2. CD3-CD56+ thymocyte NK effectors
      express the zeta protein as a disulphide-linked homodimer of 32 kDa, yet lack
      other protein components of the CD3-TCR complex. Both CD16+ and CD16- populations
      were found to express zeta, and within the CD16+ fraction, zeta is physically
      associated with CD16. These data provide evidence of additional similarities
      between adult peripheral blood NK cells and CD3-CD56+ NK effectors derived from
      human thymocytes, and suggest that under these experimental conditions, human NK
      cells can arise from early thymic precursors.

PMID- 7514107
TI  - Lack of "determinant spread" to the minor encephalitogenic epitope in myelin
      basic protein-induced acute experimental autoimmune encephalomyelitis in the rat.
AB  - Acute and monophasic experimental autoimmune encephalomyelitis (EAE) was induced
      in rats by immunization with myelin basic protein (MBP). Proliferative responses
      of lymph node cells to major and minor encephalitogenic and nonencephalitogenic
      determinants of the MBP molecules were measured at various time intervals after
      the immunization. Results of these experiments revealed that additional responses
      to minor determinants which had been observed at the late stage of mouse EAE
      (Lehmann et al., Nature 356, 155, 1992) were very weak and short-lived in the
      rat. Furthermore, the response to the minor encephalitogenic determinant was not
      recognized throughout the course of EAE. Coimmunization with synthetic peptides,
      corresponding to the major and minor determinants, induced T-cell response only
      to the major determinant. These findings suggest that poor generation of T cells
      reactive with the minor encephalitogenic epitope is attributable to peptide
      competition between these two determinants. The present results, together with
      those reported in mice, strongly suggest that differences in the clinical course
      of EAE, i.e., acute monophasic or chronic relapsing, is closely related to the
      presence or absence of "determinant spread" to minor encephalitogenic epitope(s).

PMID- 7514108
TI  - Adenovirus-mediated gene transfer of soluble vascular cell adhesion molecule to
      porcine interposition vein grafts.
AB  - BACKGROUND: The efficacy of aorto-coronary vein grafting is limited by early
      graft thrombosis and accelerated graft atherosclerosis. Direct adenovirus
      mediated transfer of genes encoding inhibitory proteins may prevent or slow
      progression of vein graft disease. METHODS AND RESULTS: Recombinant adenoviruses
      containing the cDNA for the marker gene lacZ (Ad.CMVlacZ) or soluble vascular
      cell adhesion molecule (sVCAM) (Ad.CB-sVCAM) were used to infect segments of
      porcine jugular vein or human saphenous vein. Ex vivo testing showed expression
      of the introduced genes after incubation with Ad.CMVlacZ or Ad.CBsVCAM for
      periods from 1 to 24 hours, with an increase in transfection efficiency with
      increasing incubation time. Porcine jugular veins were then interposed as
      vascular grafts in the carotid arteries of four juvenile farm pigs after ex vivo
      gene transfer by incubation for 90 to 120 minutes with Ad.CMVlacZ or Ad.CBsVCAM.
      sVCAM-transfected carotid vein grafts were placed on one side and lacZ
      transfected veins were placed contralaterally as controls. Three days later, the
      vein graft segments were resected. Expression of the lacZ gene was confirmed by X
      Gal chromagen staining and visualization by light and transmission electron
      microscopy. Gene expression was apparent in all layers of the vein graft wall,
      with prominent staining in the adventitia. sVCAM expression was confirmed by
      immunohistochemistry and in situ hybridization. CONCLUSIONS: We conclude that ex
      vivo gene transfer before vein grafting is feasible using a replication-deficient
      recombinant adenovirus and results in a high level of gene expression in vivo.
      The potential for this approach to prevent early vein graft thrombosis or
      accelerated vein graft atherosclerosis requires further evaluation.

PMID- 7514109
TI  - Nitric oxide regulates basal systemic and pulmonary vascular resistance in
      healthy humans.
AB  - BACKGROUND: The endothelium synthesizes and releases a relaxing factor with the
      physiochemical properties of nitric oxide (NO). However, the role of endothelium
      derived NO in the basal regulation of systemic and pulmonary vascular resistance
      in humans is not known. Our primary objectives were to determine the effects of
      inhibiting NO synthesis on blood pressure and systemic vascular resistance and to
      establish the role of endothelium-derived NO in the regulation of normoxic
      pulmonary vascular tone. METHODS AND RESULTS: We studied the systemic and
      pulmonary hemodynamic effects of NG-monomethyl-L-arginine (L-NMMA, 0.03 to 1.0
      mg.kg-1.min-1 IV), an NO synthase inhibitor, in 11 healthy volunteers, aged 33 +/
      2 years. An arterial cannula and a pulmonary artery catheter were placed in each
      subject to measure blood pressure, pulmonary artery pressure, and pulmonary
      capillary wedge pressure. Cardiac output was determined by the Fick technique,
      and systemic and pulmonary vascular resistances were calculated. Serum NO levels
      (free and protein bound) were measured by chemiluminescence in 5 subjects. Six of
      the subjects also received phenylephrine (25 to 100 micrograms/min IV) to compare
      the cardiac hemodynamic effects of L-NMMA with those of a direct-acting
      vasoconstrictor. L-NMMA caused dose-dependent increases in both blood pressure
      and systemic vascular resistance. At the highest dose of L-NMMA, there was a 15.5
      +/- 1.3% increase in mean blood pressure and a 63.4 +/- 8.2% increase in systemic
      vascular resistance (each P < .01). Pulmonary vascular resistance increased 39.8
      +/- 9.4% (P < .01), whereas mean pulmonary artery pressure did not change.
      Administration of L-NMMA also reduced cardiac output by 27.8 +/- 2.9% and stroke
      volume by 15.4 +/- 3.5% (each P < .01). Serum NO levels decreased 65 +/- 10% from
      basal values (P < .05), confirming inhibition of endogenous NO production.
      Phenylephrine increased blood pressure to a level comparable to that observed
      with L-NMMA. The decline in stroke volume was greater with L-NMMA than with
      phenylephrine (P < .01). CONCLUSIONS: This study demonstrates that basal release
      of endothelium-derived NO is directly involved in the determination of systemic
      vascular resistance and, therefore, blood pressure in healthy humans. In
      addition, NO regulates basal normoxic pulmonary vascular tone. The complex
      hemodynamic effects of NO are composite properties of its actions on systemic and
      pulmonary vascular resistance and cardiac function.

PMID- 7514110
TI  - Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by
      vascular endothelial growth factor in dogs.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell
      specific mitogen that is angiogenic in vitro and in vivo. It has been
      hypothesized that VEGF plays a role in myocardial collateral formation; however,
      the effects of VEGF on collateral flow to ischemic myocardium are unknown.
      METHODS AND RESULTS: We studied the effect of VEGF on collateral blood flow in
      dogs subjected to gradual occlusion of the left circumflex coronary artery (LCx).
      Beginning 10 days after placement of an LCx-constricting device, VEGF 45
      micrograms (n = 9) or saline (n = 12) was administered daily via an indwelling
      catheter in the distal LCx, at a point just beyond the occlusion. Treatment was
      maintained for 28 days. Collateral blood flow was determined with microspheres 7
      days before treatment, immediately before treatment (day 0), and 7, 14, 21, and
      28 days into the treatment period. Collateral blood flow was quantified during
      chromonar-induced maximal vasodilation and expressed as a collateral zone/normal
      zone (CZ/NZ) ratio. Treatment with VEGF was associated with a 40% increase in
      collateral blood flow (final CZ/NZ blood flow ratios of 0.49 +/- 0.06 and 0.35 +/
      0.02 in the VEGF-treated and control groups, respectively, P = .0037) as well as
      an 89% increase in the numerical density of intramyocardial distribution vessels
      (> 20 microns diameter) in the CZ (6.6 +/- 1.4 versus 3.5 +/- 0.7 vessels/mm2 in
      VEGF-treated and control dogs, respectively, P < .05). CONCLUSIONS: We conclude
      that intracoronary VEGF enhances the development of small coronary arteries
      supplying ischemic myocardium, resulting in marked augmentation of maximal
      collateral blood flow delivery. These results demonstrate the feasibility of
      pharmacological enhancement of collateral growth and suggest a new therapeutic
      approach for the treatment of myocardial ischemia.

PMID- 7514111
TI  - Fibrinolysis-resistant fibrin deposits in minor labial salivary glands of
      patients with Sjogren's syndrome.
AB  - Minor labial salivary glands obtained at biopsy from 12 patients with Sjogren's
      syndrome were investigated by immunomorphological methods for the presence of
      fibrinolysis-resistant fibrin deposition. Fibrin could be found in extracellular
      localization between individual inflammatory cells infiltrating minor salivary
      glands. In the areas surrounding mononuclear infiltrations the labeling for
      fibrin showed an essentially fibrillar pattern. Staining for factor XIII A was
      observed over fibrin deposits and in large, stellate cells not showing reaction
      for fibrin. Here it is demonstrated that factor XIII A+ tissue macrophages are in
      an intimate relationship with fibrin deposits. The authors suggest that tissue
      macrophages may play a regulatory role in fibrin accumulation in association with
      autoimmune inflammation and consequently in demarcation of the inflamed tissue.

PMID- 7514112
TI  - Serum IgA cross-reactivity between glycine-alanine repeat sequence of EBNA-1 and
      keratin or collagen in nasopharyngeal carcinoma.
AB  - Inhibition studies were carried out to study possible cross-reactivity between a
      peptide fragment of the Epstein-Barr virus nuclear antigen, EBNA-1, and
      keratin/collagen. The 20-amino acid peptide (pAG), derived from a glycine-alanine
      repeat region of EBNA-1, uniquely makes up about one-third of the viral protein
      and is a dominant IgA antigenic epitope in patients with nasopharyngeal carcinoma
      (NPC). A small percentage of normal human sera (NHS) also binds pAG and this
      reactivity is examined in this study. Ten percent (2/20) and 13.4% (2/15) of IgA
      pAG-positive NPC sera and NHS, respectively, were significantly inhibited by
      keratin in a competitive ELISA system. Conversely, 31.6% (6/19) and 30.8% (4/13)
      of IgA-keratin-positive NPC sera and NHS, respectively, were significantly
      inhibited by pAG. This indicated minimum cross-reactivity between IgA serum
      antibodies to EBNA-1 and keratin. Using collagen as inhibitor, none of 18 and
      only 2/13 IgA-pAG-positive NPC sera and NHS, respectively, were inhibited. In the
      collagen ELISA system, only 2/19 (10.5%) and 4/25 (16%) of IgA-collagen-positive
      NPC sera and NHS, respectively, were inhibited with pAG. Therefore, cross
      reactivity with collagen was also low. IgA-pAG-positive NHS may therefore not be
      a false positive phenomenon, but whether it may represent an early serological
      profile related to NPC carcinogenesis remains to be determined.

PMID- 7514113
TI  - Dynamic state of beta 2 integrin phosphorylation: regulation of neutrophil
      aggregation involves a phosphatase-dependent pathway.
AB  - The role of phosphorylation and dephosphorylation events in homotypic neutrophil
      aggregation mediated by CD11b/CD18 molecules was investigated using okadaic acid,
      an inhibitor of serine and threonine phosphatases. In the absence of exogenous
      stimuli the addition of okadaic acid to neutrophils resulted in a dose-dependent
      increase in phosphorylation of the CD18 beta chain that was further augmented by
      PMA but unaffected by FMLP. Phosphorylation induced by okadaic acid was reversed
      by staurosporine and minimally decreased by the less selective PKA/PKC
      inhibitors, H-7 and H-8. This suggests the existence of constitutive phosphatase
      and kinase activity emphasizing the dynamic state of phosphorylation and
      dephosphorylation of the beta 2 integrins. Unlike PMA, okadaic acid did not
      promote homotypic neutrophil aggregation. Furthermore, both the PMA-induced
      pathway of irreversible aggregation, blocked by staurosporine, as well as the
      FMLP-induced pathway of reversible aggregation, augmented by staurosporine, were
      inhibited by okadaic acid in a dose- and time-dependent manner. These results
      provide evidence that a phosphatase-dependent step is involved in each of these
      two distinct pathways that regulate neutrophil aggregation mediated by beta 2
      integrin activation.

PMID- 7514114
TI  - Induction of nitric oxide synthase in subsets of murine pulmonary fibroblasts:
      effect on fibroblast interleukin-6 production.
AB  - The purpose of this investigation was to determine whether mouse lung fibroblast
      subsets have the ability to produce nitric oxide (NO), and if so, to characterize
      the induction and effects of its synthesis. Previously, we isolated Thy1+ and
      Thy1- subpopulations of mouse lung fibroblasts, which differ in terms of cytokine
      production, morphology, response to cytokines and radiation, and ability to
      present antigen to T lymphocytes. When treated with the proinflammatory cytokines
      IFN-gamma, TNF-alpha, and IL-1 alpha, these fibroblast lines produce micromolar
      quantities of NO2- and NO3-, two stable end products of the NO pathway. A
      combination of all three cytokines provided the greatest induction, and there was
      no measurable production of NO in unstimulated cells. Thy1+ fibroblasts have
      fewer requirements for induction of NO production than the Thy1- line, in that NO
      production could be induced by only two of the above cytokines, where the Thy1-
      fibroblasts required all three. Inducible NO synthase (iNOS) mRNA was shown to be
      present by the reverse transcriptase-polymerase chain reaction as early as 2 hr
      after cytokine treatment in both cell lines. Addition of the NO synthase
      inhibitors NG-monomethyl-L-arginine and aminoguanidine inhibited production of
      NO2- and NO3-, but not iNOS mRNA. This inhibition was partially reversed by the
      addition of an excess of L-arginine. Interestingly, inhibition of NO synthesis
      was shown to decrease IL-6 production by more than 50% in cytokine-treated Thy1+
      fibroblasts. These results indicate for the first time that Thy1+ and Thy1- mouse
      lung fibroblast subsets have the capability to produce NO to differing extents in
      response to cytokines and may therefore play an important role in the
      inflammatory response in the lung as well as in the progression of lung disease.

PMID- 7514115
TI  - Immunoglobulin variable region usage in human intestinal B lymphocytes.
AB  - The B cell repertoire was studied in intestinal mononuclear cells from normal
      individuals and patients with inflammatory bowel disease (IBD) by examining Ig
      heavy chain variable gene (VH) usage. Using reverse transcription of intestinal
      mucosal RNA followed by polymerase chain reaction with primers specific for each
      VH family and a housekeeping gene, a semiquantitative assay of VH family content
      in RNA samples was developed. While all VH family members were expressed,
      differences in VH usage in lamina propria intestinal B cells were noted between
      Crohn's disease, ulcerative colitis, and normal individuals. mRNA transcripts for
      VH4 were present at seemingly higher levels than their genomic representation and
      transcripts for VH1 and VH4 appeared to have higher levels in active, compared to
      inactive, IBD. Thus, within the massive polyclonal intestinal B cell response,
      there is a skewed VH usage which may be relevant to the antigenic and/or
      autoimmune response noted in IBD.

PMID- 7514116
TI  - Influence of surgery on serum concentrations of hyaluronan.
AB  - OBJECTIVE: To investigate the changes in serum hyaluronan concentrations in
      response to surgery. DESIGN: A prospective case series evaluating serum
      hyaluronan concentrations before, during, and after surgery. SETTING: Operating
      room and recovery room of a university hospital. PATIENTS: Twelve consecutive
      patients undergoing vascular surgery because of arterial insufficiency of the
      lower extremities. MEASUREMENTS AND MAIN RESULTS: Serum hyaluronan concentrations
      were measured before and after induction of anesthesia and before, during, and
      after surgery. Routine chemical analyses of blood samples were made before and
      after surgery. Blood loss and fluid volumes infused were registered. Mean serum
      hyaluronan concentrations increased from baseline 25 +/- 10 (SD) to 36 +/- 15
      micrograms/L (p < .05) during surgery, and increased further at 1 hr after the
      end of surgery to 52 +/- 38 micrograms/L (p < .001 compared with baseline), but
      had decreased nearly to baseline levels at 2 hrs postoperatively. A positive
      correlation was seen between peak hyaluronan concentrations and baseline serum
      hyaluronan levels (r2 = .73; p < .001), but no strong relationship was seen
      between serum hyaluronan concentrations and other parameters studied.
      CONCLUSIONS: Surgery is accompanied by a small increase in serum hyaluronan
      concentrations in humans. The major increase is seen in the postoperative period,
      and is probably due to increased influx of interstitial hyaluronan when the
      returning muscular tone activates lymph flow.

PMID- 7514117
TI  - Two-color analysis of lymphocyte subsets of bronchoalveolar lavage fluid and
      peripheral blood in Japanese patients with sarcoidosis.
AB  - Analysis of T-cell surface markers was carried out in peripheral blood and
      bronchoalveolar lavage (BAL) fluid of Japanese patients with sarcoidosis to
      examine the influence of differing racial background. The subjects were 26
      untreated patients in whom a diagnosis of active sarcoidosis had recently been
      established and 9 healthy volunteers, and two-color immunofluorescence analysis
      was performed. CD3+HLA-DR+ cells, CD4+HLA-DR+ cells, and CD4+CD29+ cells in
      peripheral blood and BAL fluid were significantly increased in the patients
      compared with the healthy volunteers, and the mean percentages increased in
      parallel with the extent of the radiologic stage. The percentage of CD3+HLF-DR+
      cells in peripheral blood and lavage fluid also significantly correlated with
      serum activity of angiotensin-converting enzyme (r = 0.69, p < 0.001; r = 0.61, p
      < 0.001, respectively). Thus, the evaluation of these antigens' expression is an
      important clinical approach for the staging of the disease. However, no
      significant differences were found in CD3+CD25+, CD4+CD45RA+, or CD8+CD11+ cells
      in either peripheral blood or BAL fluid between the patients and volunteers. Our
      results indicated that in Japanese patients with sarcoidosis, circulating T cells
      are activated but CD25+ cells are not increased in peripheral blood and BAL
      fluid, but there is not a significant association with racial background.

PMID- 7514118
TI  - Pseudo-atrioventricular dissociation caused by interpolated ventricular
      extrasystoles in the presence of dual atrioventricular nodal pathway.
AB  - This report describes a patient manifesting with ventricular extrasystoles. The
      pause occasioned by extrasystoles often is followed by narrow QRS complexes not
      preceded by P waves, but at times is followed by a sinus P wave. At first glance,
      the pattern suggests a diagnosis of atrioventricular (A-V) junctional escape
      complexes. Analysis reveals that ventricular extrasystoles are, in fact,
      interpolated; the sinus P wave that follows the extrasystole is conducted to the
      ventricles with a very prolonged P-R interval (up to 0.80 s). The phenomenon is
      due to the presence of a dual A-V nodal pathway. The sinus impulse that follows
      the extrasystole is blocked in the fast pathway but may still be conducted to the
      ventricles through the slow pathway, resulting i a very prolonged P-R interval.

PMID- 7514119
TI  - Amylase concentrations in pleural effusions.

PMID- 7514120
TI  - The potential of nosocomial transmission of Pseudomonas cepacia exists at
      cardiopulmonary transplant centers.

PMID- 7514121
TI  - Postpneumonectomy lung growth following thyroparathyroidectomy.
AB  - Hormonal regulation of compensatory lung growth is not well understood, but it
      may be similar to that during compensatory growth of other organs. Liver
      regeneration is blocked by hypocalcemia in thyroparathyroidectomized (TPX)
      animals. Although calcium status is an important regulator of growth in many
      biological systems, the effect of TPX on compensatory lung growth is unknown. In
      male Sprague-Dawley rats, TPX lowered blood ionized calcium by 42% (p < .01)
      within two days; it remained depressed for at least one additional week. Thyroid
      intact and TPX animals were therefore subjected either to sham thoracotomy or to
      left pneumonectomy on post-TPX day 2. Growth of the right lung was assessed on
      day 9 when, in pneumonectomized animals, lung mass had increased 23% (p < .01).
      TPX had no effect on right lung mass in sham animals. Similarly, TPX had no
      effect on the postpneumonectomy increase in right lung mass, which reached 118%
      (p < .01) of that in TPX controls. Analysis of right lung DNA, RNA, and protein
      concentrations on day 9 revealed that tissue macromolecule content increased
      postoperatively in both PNX and TPX/PNX rats in proportion to lung growth. These
      results demonstrate that postpneumonectomy compensatory growth of the lung is not
      blocked in the thyroparathyroprivic hypocalcemic rat.

PMID- 7514122
TI  - Biochemical mechanisms for the attenuation of bleomycin-induced lung fibrosis by
      treatment with niacin in hamsters: the role of NAD and ATP.
AB  - Treatment with niacin (NA), a precursor of NAD, has been shown to attenuate
      collagen accumulation in the bleomycin (BL) hamster model of lung fibrosis. This
      study investigated the effects of NA on lung levels of NAD, ATP, ADP, and AMP
      during various stages of lung fibrosis caused by intratracheal (IT) instillation
      of BL in hamsters. Niacin (500 mg/kg, IP) or saline (SA, IP) was given daily two
      days prior to and every day after the IT administration of BL (7.5 U/5 mL/kg) or
      an equivalent volume of sterile isotonic saline. Hamsters were sacrificed at 1,
      4, 7, 10, and 14 days after BL or saline treatment. Lung NAD, ATP, ADP, and AMP
      were separated and quantitated using C-18 reverse-phase HPLC coupled with UV
      detection. The lung ATP content of the SABL groups was significantly (p < or =
      .05) increased at 1, 7, 10, and 14 days, peaking at 7 days to 210 +/- 20% of the
      SASA group. The hamsters in NABL groups also had significant increases in ATP
      levels at 7, 10, and 14 days, peaking to 172 +/- 18% of the NASA group at 7 days.
      ATP levels in the NABL groups were significantly higher than SABL groups at 10
      and 14 days. There were small changes in the lung levels of ADP and AMP among the
      various treated groups. The lung NAD content of the SABL group was significantly
      decreased compared to the SASA group at 7 and 10 days, with a nadir of 66 +/- 13%
      at 10 days. The lung NAD content in the NABL group was significantly higher than
      that of the SABL group at 10 and 14 days. There was no significant difference in
      lung NAD content between the NABL and NASA groups. The results of this study
      suggest that depletions of NAD and ATP play a pivotal role in the pathogenesis of
      BL-induced lung toxicity, and treatment with NA minimizes this toxicity by
      increasing and/or maintaining the intracellular levels of NAD and ATP of the
      lungs.

PMID- 7514123
TI  - Structural organization of the genes for rat von Ebner's gland proteins 1 and 2
      reveals their close relationship to lipocalins.
AB  - The rat von Ebner's gland protein 1 (VEGP 1) is a secretory protein, which is
      abundantly expressed in the small acinar von Ebner's salivary glands of the
      tongue. Based on the primary structure of this protein we have previously
      suggested that it is a member of the lipocalin superfamily of lipophilic-ligand
      carrier proteins. Although the physiological role of VEGP 1 is not clear, it
      might be involved in sensory or protective functions in the taste epithelium.
      Here, we report the purification of VEGP 1 and of a closely related secretory
      polypeptide, VEGP 2, the isolation of a cDNA clone encoding VEGP 2, and the
      isolation and structural characterization of the genes for both proteins. Protein
      purification by gel-filtration and anion-exchange chromatography using Mono Q
      revealed the presence of two different immunoreactive VEGP species. N-terminal
      sequence determination of peptide fragments isolated after protease Asp-N
      digestion allowed the identification of a new VEGP, named VEGP 2, in addition to
      the previously characterized VEGP 1. The complete VEGP 2 sequence was deduced
      from a cDNA clone isolated from a von Ebner's gland cDNA library. The VEGP 2 cDNA
      encodes a protein of 177 amino acids and is 94% identical to VEGP 1. DNA sequence
      analysis of the rat VEGP 1 and 2 genes isolated from rat genomic libraries
      revealed that both span about 4.5 kb and contain seven exons. The VEGP 1 and 2
      genes are non-allelic distinct genes in the rat genome and probably arose by gene
      duplication. The high degree of nucleotide sequence identity in introns A-C (94
      100%) points to a recent gene conversion event that included the 5' part of the
      genes. The genomic organization of the rat VEGP genes closely resembles that
      found in other lipocalins such as beta-lactoglobulin, mouse urinary proteins
      (MUPs) and prostaglandin D synthase, and therefore provides clear evidence that
      VEGPs belong to this superfamily of proteins.

PMID- 7514124
TI  - Nonmetastatic gestational trophoblastic disease. Weekly methotrexate compared
      with 8-day methotrexate-folinic acid.
AB  - The efficacy of single agent chemotherapy with methotrexate in low risk
      gestational trophoblastic disease is well established, but efforts to reduce
      toxicity and patient time and cost continue. Twenty-five patients with
      nonmetastatic postmolar gestational trophoblastic disease were seen by the
      Division of Gynecologic Oncology at the University of South Florida between
      February 1986 and December 1991. Patients were treated with either weekly
      intramuscular methotrexate 40 mg/M2 (Group 1, n = 13) or alternating doses of
      intramuscular methotrexate 1 mg/kg and folinic acid 0.1 mg/kg over eight
      consecutive days with an eight- day interval (Group 2, n = 12). Patient age, body
      weight and pre-treatment beta-hCG values were similar in the two groups. One
      patient defaulted from treatment and was lost to follow-up. All other patients
      were cured. Complete remission was achieved with primary chemotherapy in nine
      (69%) patients in Group 1 and nine (75%) in Group 2. All patients with pre
      treatment beta-hCG of 650 mIU/ml or less responded to primary therapy whereas 50%
      of those with higher levels required second-line therapy. When secondary and
      tertiary treatment were included, the duration of treatment was similar in both
      groups. Remission was achieved at significantly lower levels of methotrexate in
      group 1 patients (p < 0.001). No major toxicities occurred. Side effects were
      gastrointestinal and myelosuppressive and occurred in 2.5% and 15.6% of treatment
      cycles in Groups 1 and 2, respectively (p < 0.01). Weekly methotrexate is an
      equally effective and less toxic regimen than eight-day methotrexate-folinic acid
      in nonmetastatic postmolar gestational trophoblastic disease.

PMID- 7514125
TI  - T cells of staphylococcal enterotoxin B-tolerized autoimmune MRL-lpr/lpr mice
      require co-stimulation through the B7-CD28/CTLA-4 pathway for activation and can
      be reanergized in vivo by stimulation of the T cell receptor in the absence of
      this co-stimulatory signal.
AB  - The CD28/CTLA-4 receptors on T cells interact with the B7 molecule on antigen
      presenting cells (APC) to produce a co-stimulatory signal that determines the
      outcome of activation. The role of this co-stimulatory signal in T cell
      activation and loss of tolerance in autoimmune MRL-lpr/lpr mice has not been
      investigated previously. The present study examines the contribution of the
      CD28/CTLA-4 co-stimulatory pathway to the loss of T cell tolerance in V beta 8
      transgenic MRL-lpr/lpr and (-)+/+ mice in which neonatal tolerance has been
      induced by the superantigen staphylococcal enterotoxin B (SEB). An artificial APC
      transfected with the murine B7 gene, and a CTLA-4-Ig fusion protein were used to
      analyze the significance of the CD28/CTLA-4 pathway in vitro. The CTLA-4-Ig
      fusion protein was also used to inhibit the pathway in vivo. Our results
      demonstrate that CD28 and CTLA-4 mRNA was overexpressed in the lymph nodes of
      lpr/lpr mice (MRL, C57BL/6, C3H and AKR), but not in +/+ mice of the same
      background strain. Lymph node T cells and thymocytes from SEB neonatally
      tolerized MRL-lpr/lpr mice that had undergone tolerance loss, proliferated when
      cultured with SEB and B7+ fibroblasts in vitro, but did not proliferate when the
      SEB was presented in the context of B7- fibroblasts. This in vitro tolerance loss
      could be prevented by blocking of B7 signaling by CTLA-4-Ig. This loss of
      tolerance did not occur in lymph node T cells from thymectomized MRL-lpr/lpr
      mice. SEB challenge of tolerized MRL-lpr/lpr mice in vivo led to weight loss,
      increased serum cytokine levels and depletion of V beta 8+ T cells. These effects
      were blocked by blocking of the co-stimulatory pathway by treatment with the CTLA
      4-Ig fusion protein prior to and during challenge with SEB. T cells from thymus
      and lymph nodes of these mice did not proliferate later in response to
      stimulation in vitro with SEB even in the presence of B7+ APC. Nonresponsiveness
      was not due to deletion of V beta 8+ CD28+ T cells, as the number of these cells
      was increased after treatment with SEB and the CTLA-4-Ig fusion protein.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7514126
TI  - Orally administered myelin basic protein in neonates primes for immune responses
      and enhances experimental autoimmune encephalomyelitis in adult animals.
AB  - Antigen-driven tolerance is an effective method for suppression of autoimmune
      diseases. Adult animals can be tolerized against the induction of experimental
      autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of
      myelin basic protein (MBP). We have found that in contrast to previous studies of
      neonatal tolerance in which parenterally administered autoantigens induced
      tolerance, the oral administration of MBP in neonatal rats did not result in
      tolerization to MBP, but instead, primed for immunologic responses. Proliferative
      responses to MBP and its encephalitogenic epitope were present in animals fed
      with MBP as neonates and co-culture of encephalitogenic T cells with cells from
      neonatal rats fed with MBP were associated with enhanced MBP responses rather
      than the suppression observed with cells from adult rats fed with MBP.
      Furthermore, neonates fed with MBP and immunized 6-8 weeks later with MBP in
      adjuvant to induce EAE revealed enhancement of disease severity, and were not
      protected from a second attack upon active reinduction of EAE. Subcutaneous
      injection of soluble MBP into neonates had no effect on EAE induction as adults,
      whereas intraperitoneal injection of MBP in neonates was associated with marked
      suppression of disease in adults. Suppression of EAE began to appear in animals
      fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult
      animals when animals were fed at 6 weeks of age. These results suggest that
      immaturity of the immunoregulatory network associated with oral tolerance and
      sensitization to autoantigens via the gut in the neonatal period may contribute
      to the pathogenesis of autoimmune diseases.

PMID- 7514127
TI  - Isolation of peritoneal precursors of B-1 cells in the adult mouse.
AB  - Two weeks of daily peritoneopheresis of adult mice result in the selective
      depletion of B-1 cells, followed by the appearance of a population of B220+IgM
      lymphocytes in the peritoneal cavity. These cells share with bone marrow (BM) pre
      B cells expression of lambda 5, VpreB, and RAG-1 genes and a higher fraction of
      unrearranged V to DJ heavy (H) chain immunoglobulin (Ig) gene segments, when
      compared with mature B lymphocytes. Upon transfer to SCID recipients, sorted
      peritoneal B220+IgM- cells fail to colonize the BM, repopulate very few B cells
      in the spleen, but entirely reconstitute the B-1 cell compartment in the
      peritoneal and pleuropericardial cavities. In contrast, parallel transfers of
      sorted BM and pleuropericardial cavities. In contrast, parallel transfers of
      sorted BM B220+IgM- cells result in reconstitution of the BM and spleen B lineage
      cell compartments, but in no coelomic B cell repopulation. Both types of pre-B
      cells reconstitute splenic plasma cells of donor origin, but with markedly
      distinct efficiencies: the ratio of IgM-plasma cell/B cell numbers in the spleens
      of peritoneal pre-B cell recipients is more than 500-fold higher than that of
      recipients reconstituted by BM pre-B cells. We take these data to indicate that
      (1) differentiative commitment to the B-1 cell population occurs before selection
      events on mature cells; (2) B-1 precursors exist or may be locally produced in
      the adult mouse; (3) there is a lineage-related differential ability of mature B
      cells to undergo terminal differentiation to high-rate Ig secretion.

PMID- 7514128
TI  - Inhibition of entire myelin basic protein-induced experimental autoimmune
      encephalomyelitis in Lewis rats by major histocompatibility complex class II
      binding competitor peptides.
AB  - Previous studies have shown that major histocompatibility complex (MHC) blockade
      by competitor peptides with high MHC class II binding affinity can prevent
      peptide-induced experimental autoimmune encephalomyelitis (EAE). However, none of
      these studies addressed the question whether this approach could also be used to
      prevent EAE induced with a multivalent antigen. In this report we show the effect
      of competitor peptides co-immunized during EAE induction with entire guinea pig
      myelin basic protein (MBP) in Lewis rats. As MHC class II binding competitor
      peptides we used one nonimmunogenic disease-nonrelated peptide, and two
      immunogenic peptides, one EAE-related and one non-EAE-related. The respective
      efficacy of these three competitor peptides to inhibit MBP-induced proliferation
      of an encephalitogenic T cell line in vitro correlated with their respective MHC
      binding affinity. Co-immunization of the competitor peptides during disease
      induction with entire MBP resulted in a competitor concentration-dependent
      inhibition of clinical signs of EAE. These results demonstrate that, although
      polyclonal T cell responses to MBP were not completely inhibited, co
      administration of immunogenic or nonimmunogenic either EAE-related or non-EAE
      related MHC class II binding competitor peptides can inhibit the development of
      EAE induced with entire MBP.

PMID- 7514131
TI  - T cell subset distribution and B cell hyperreactivity in mice expressing
      interleukin-4 under the control of major histocompatibility complex class I
      regulatory sequences.
AB  - Transgenic mice in which interleukin-4 (IL-4) is expressed under the control of
      the major histocompatibility complex (MHC) class I regulatory sequences show low
      level expression of IL-4 in all organs investigated. Several weeks after birth
      the animals develop thymus hypoplasia with a loss of CD4+CD8+ double-positive
      cells and a relative increase in the mature population, especially, and in
      contrast to previously published lines, the CD4+ single-positive cells. In the
      periphery, T lymphocytes eventually decline, CD8+ cells being more strongly
      affected. Many of the residual T cells exhibit the CD44highMel-14low phenotype of
      antigenically experienced T cells. B cells also show an activated phenotype with
      respect to size, MHC class II and CD23 expression, are more readily stimulated by
      anti-mu F(ab')2 antibodies than are B cells from control littermates, and show a
      higher spontaneous and antigen-induced production of IgG1 and IgE.

PMID- 7514132
TI  - Vaccination with T cell receptor peptides primes anti-receptor cytotoxic T
      lymphocytes (CTL) and anergizes T cells specifically recognized by these CTL.
AB  - We selected three peptides from the germ-line sequence of the V beta 8.2 and J
      beta 2.3 gene segments of the murine T cell receptor for antigen (TCR) which
      contained putative Kd- and Ld-restricted epitopes. Immunization of BALB/c (H-2d)
      mice with the V beta 8.2(67-90) 23-mer peptide 1 as well as the 15-mer V beta
      8.2(95-108)-peptide 2 efficiently primed specific CD8+ cytotoxic T lymphocyte
      (CTL) responses in vivo against natural TCR-V beta 8.2 epitopes. V beta 8.2+ T
      cells were not deleted in TCR peptide-immunized mice because the fractions of V
      beta 8.2+ CD4+ and V beta 8.2+ CD8+ T cells in spleen and lymph nodes were not
      altered. The proliferative response of V beta 8.2+ T cells to stimulation by
      monoclonal antibody F23.2 was selectively suppressed (by 60-80%) in peptide
      immunized BALB/c mice, indicating partial anergy of this T subset. Immunization
      of BALB/c mice with the J beta 2.3-derived peptide 3 stimulated a CD8+ CTL
      response against a class I-restricted epitope within this J beta segment that was
      also generated during natural "endogenous" processing of this self antigen. These
      data confirm the predictive value of major histocompatibility complex class I
      allele-specific motifs. The described experiments indicate that TCR peptide
      primed CD8+ CTL recognize class I-restricted, natural V beta/J beta-TCR epitopes.
      Such anti-TCR CTL may, thus, operate in V beta-specific immunoregulation of the T
      cell system suppressing their functional reactivity without deleting them.

PMID- 7514130
TI  - Degeneracy of T cell receptor recognition of an influenza virus hemagglutinin
      epitope restricted by HLA-DQ and -DR class II molecules.
AB  - DT9301-0229737 the TcR are believed to provide the peptide fragments bound to
      major histocompatibility (MHC) molecules. TcR have an immunoglobulin (Ig)-like
      structure and, in an analogous manner to antigen recognition by Ig, the third
      complementarity determining regions (CDR3) of the TcR are believed to provide the
      primary contact with the peptide lying in the MHC groove. CDR1 and CDR2 are
      thought to contact the presenting MHC molecule. We have analyzed seven human CD4+
      T cell clones that recognize a conserved peptide epitope (residues 255-270)
      within the influenza virus hemagglutinin (H3) HA1 subunit. Two T cell clones
      recognized the peptide in the context of HLA-DRB1*1001 and HLA
      DQB1*0602/DQA1*0102, respectively, and shared V alpha, V beta and J beta gene
      segments. Only the junctional regions encoding the CDR3 regions of the two TcR
      chains were different. This suggests that the CDR3 regions of these TcR interact
      with the MHC class II molecule. Six of the T cell clones were restricted by the
      HLA-DRB1*1001. Two of these T cell clones expressed V beta 9.1 and three
      expressed V beta 13 gene segments; the remaining clone expressed V beta 7.2, a
      close homologue of V beta 9.1. A diverse selection of V alpha and J gene segments
      contributed to the junctional heterogeneity of the TcR, indicating a diversity of
      sequence combinations recognizing the epitope. Nevertheless, five out of six T
      cell clones bore a motif in the V alpha CDR3 loop consisting of adjacent acidic
      and polar amino acid residues, eight residues from the carboxyl end of each CDR3.

PMID- 7514129
TI  - Sialyl Lewis(x)- and L-selectin-dependent site-specific lymphocyte extravasation
      into renal transplants during acute rejection.
AB  - Kidney allograft rejection is an inflammatory process dominated by lymphocytes.
      During rejection lymphocytes preferentially adhere to the peritubular capillary
      endothelium (PTCE), which acquires morphological features common to high
      endothelium. These observations indicate that PTCE is the site of lymphocyte
      entry into the rejecting renal allograft. Of the identified endothelial adhesion
      molecules, ICAM-1 was already expressed on the endothelium of normal kidneys, and
      its expression was strongly enhanced during rejection without site-specific
      restriction. VCAM-1 was not expressed on the endothelium of normal or syngeneic
      kidneys, but its expression was induced during allograft rejection not only in
      PTCE, but occasionally also on the endothelium of larger vessels. Sialyl Lewisx
      (sLex) showed a very restricted pattern of expression; endothelium was sLex
      negative both in control and syngeneic kidneys. On the other hand, PTCE reacted
      strongly with anti-sLex antibody in allografts. When kidney frozen sections were
      treated with sialidase the binding of lymphocytes decreased by 70%. Low-dose
      chymotrypsin treatment of lymphocytes, known to remove L-selectin from the
      lymphocyte surface, decreased their binding to PTCE by 60%. Likewise lymphocyte
      adhesion to PTCE was inhibited by 70% by anti-sLex- and anti-L-selectin
      antibodies and by sLex tetrasaccharide. Finally PTCE in the allografts, but not
      in syngeneic grafts or normal kidneys, bound an L-selectin-IgG fusion protein,
      indicating that ligands for L-selectin were induced during rejection.

PMID- 7514133
TI  - Anergic B cells constitutively present self antigen: enhanced immunoglobulin
      receptor-mediated presentation of antigenic determinants by B cells is
      hierarchical.
AB  - Presentation of hen egg lysozyme (HEL) by HEL-specific B cells was studied in
      transgenic mice expressing anti-HEL immunoglobulin (Ig-transgenic). In T
      hybridoma assays, presentation of the HEL46-61 determinant by B cells from Ig
      transgenic mice required 10(3)-10(4)-fold lower concentrations of HEL than were
      required for presentation by B cells from non-transgenic mice. In contrast,
      presentation of the HEL determinants 112-129 and 25-43 by HEL-specific B cells
      was either not significantly enhanced, or enhanced only 10-fold compared with B
      cells from non-transgenic mice. Enhanced presentation of HEL determinants by B
      cells from Ig-transgenic donors was specific for HEL, since keyhole limpet
      hemocyanin or synthetic HEL46-61 peptide were presented comparably by B cells
      from Ig-transgenic mice and non-transgenic littermates. A minimum of 1-4% Ig
      transgenic B cells was required to detect enhanced presentation of HEL46-61 in
      vitro. Constitutive presentation of the HEL46-61 determinant, but not the HEL25
      43 or HEL112-129 determinants, was detectable on anergic HEL-specific B cells
      from double (HEL/Ig)-transgenic mice. In the presence of exogenously added HEL,
      anergic B cells presented all three HEL determinants. Constitutively presented
      HEL46-61 was not due to endogenous synthesis of HEL antigen by anergic B cells
      from double-transgenic mice, as comparable levels of the HEL46-61 determinant
      were constitutively presented by B cells from Ig-Tg-->HEL-Tg irradiation bone
      marrow chimeric mice. Firstly, these results indicate that the enhanced antigen
      presentation mediated by Ig receptors on B cells is not equivalent for all
      antigenic determinants. Secondly, the data demonstrate that anergic, autoreactive
      B cells efficiently process and present nominal antigens in addition to
      constitutively presenting specific self antigen in vivo.

PMID- 7514135
TI  - Changes in thymic export of L-selectin+ gamma delta and alpha beta T cells during
      fetal and postnatal development.
AB  - We have used the technique of in situ intrathymic injection of fluorescein
      isothiocyanate to examine L-selectin expression on gamma delta and alpha beta T
      cells immediately after emigrating from the thymus of fetal and postnatal
      animals. We found that the percentage of L-selectin+ thymocytes exported per day
      decreased by half after birth and that the export of T cells from the thymus does
      not rely on expression of the peripheral lymph node homing receptor, L-selectin.
      Analysis of L-selectin on emigrant and mature T cell subsets revealed a
      remarkable heterogeneity of expression, both in terms of the numbers of cells
      expressing this molecule as well as the level of expression. gamma delta T cells,
      reportedly not having a propensity for homing to lymph nodes, not only contained
      the highest proportion of L-selectin+ cells, but also expressed far more of this
      molecule than either CD4+CD8- or CD4-CD8+ alpha beta T cells. Furthermore, those
      emigrant T cells expressing L-selectin are somewhat immature in their expression
      of this molecule. Subsequent maturation resulted in up-regulation of L-selectin
      on mature peripheral blood T cells, maturation that was clearly independent of
      extrinsic antigen. This antigen-independent post-thymic maturation appeared to
      occur as part of the normal progression from immature thymocyte to mature
      peripheral T cell in both fetal and postnatal animals.

PMID- 7514136
TI  - Processing of viable group A streptococci leads to major histocompatibility
      complex class II presentation of T cell epitopes from the major protective
      antigen.
AB  - We have previously mapped major histocompatibility complex (MHC) class II
      restricted T cell epitopes of the surface M protein of type 5 group A
      streptococci (M5) and show here that two out of four epitopes investigated were
      efficiently processed during incubation of viable streptococci with spleen cells
      for presentation to M5-specific murine T cell clones. Viable streptococci were
      processed more efficiently than heat-killed bacteria suggesting that secreted
      virulence factors of streptococci do not obstruct processing of streptococcal
      antigens in the dose range used. Epitopes from different regions of M5 could be
      ranked according to the efficiency with which they were processed, which may
      contribute to their relative immunodominance. It was further demonstrated that T
      cell clones specific for M5 308-319, an epitope from the M type conserved carboxy
      terminal half of M5, cross-reacted between M5, M6 and M12, but not M49,
      streptococci. Helper T cell epitopes which are shared between streptococcal M
      types and are presented by MHC class II molecules on antigen-presenting cells
      after processing of viable streptococci could be particularly useful in the
      design of multivalent streptococcal vaccines.

PMID- 7514134
TI  - Human anti-IgE antibodies by repertoire cloning.
AB  - Anti-IgE antibodies have been detected in sera of patients with an allergic
      disease where they might play a role in the regulation of (Ig)E-mediated
      reactions. Using a recombinant phage surface display expression system a
      combinatorial library of antibody heavy and light chains was constructed from
      peripheral blood mononuclear cells from an atopic donor immunized with tetanus
      toxoid. Screening of the library allowed the identification of a large number of
      phages displaying human monovalent antigen-binding fragments (Phab) against
      tetanus toxoid and IgE. Surprisingly, we found a high frequency of Phab against
      particular IgE myelomas that was comparable to the frequency found for Phab
      against tetanus toxoid. However, most of these Phab were directed to different
      idiotypic determinants, depending on the IgE myeloma used for the panning
      procedure. Nevertheless, two clones were found to have anti-isotypic specificity
      and were shown to react specifically with the CH2 domain of the IgE heavy chain.

PMID- 7514137
TI  - Chemical syntheses of Trolox conjugates which protect human ventricular myocytes
      against in situ-generated oxyradicals.
AB  - Synthetic conjugates of the antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethyl
      chroman-2-carboxylic acid) have been prepared by coupling it with 1-ethyl-3-(3
      dimethyl-amino-propyl) carbodiimide hydrochloride either to p-aminophenyl-beta-D
      lactopyranoside, or to higher molecular weight ligands such as dextran and
      polylysine. Compared to Trolox and on a mole to mole basis, dextran-Trolox is
      almost equally active, while lactosylphenyl- and polylysine-Trolox conjugates are
      distinctly more active in preventing the damage on human ventricular myocytes by
      oxyradicals generated from xanthine oxidase-hypoxanthine. Listed in order of
      decreasing cytoprotective activity, they are: lactosylphenyl-Trolox >> polylysine
      Trolox > Trolox > dextran-Trolox. Thus, Trolox can be chemically modified by
      coupling it to one of a number of ligands and, in some cases, with resultant
      increases in its ability to protect human ventricular myocytes from oxyradical
      damage.

PMID- 7514138
TI  - A narrow therapeutical window of a nitric oxide synthase inhibitor against
      transient ischemic brain injury.
AB  - N omega-nitro-L-arginine (0.3-10 mg/kg), a nitric oxide (NO) synthase inhibitor,
      was administered i.p. to gerbils subjected to 10 min of carotid artery occlusion
      seven times at 5 min, 3, 6, 24, 48, 72 and 96 h after recirculation.
      Histopathological examination of the brains obtained 6 days after reflow
      disclosed that N omega-nitro-L-arginine possesses an ability to mitigate neuronal
      necrosis in the CA1 subfield of the hippocampus with an optimal dosage of 3
      mg/kg. These results strongly suggest that NO synthase activation is at least
      partly involved in the pathogenetic cellular mechanisms underlying selective
      neuronal necrosis following cerebral ischemia.

PMID- 7514139
TI  - Cloning and expression of a cDNA for the human prostacyclin receptor.
AB  - A functional cDNA for the human prostacyclin receptor was isolated from a cDNA
      library of CMK cells, a human megakaryocytic leukaemia cell line. The cDNA
      encodes a protein consisting of 386 amino acid residues with seven putative
      transmembrane domains and a deduced molecular weight of 40,956. [3H]Iloprost
      specifically bound to the membrane of CHO cells stably expressing the cDNA with a
      Kd of 3.3 nM. This binding was displaced by unlabelled prostanoids in the order
      of iloprost = cicaprost >> carbacyclin > prostaglandin E1 (PGE1) > STA2. PGE2,
      PGD2 and PGF 2 alpha did not inhibit it. Iloprost in a concentration-dependent
      manner increased the cAMP level and generated inositol trisphosphate in these
      cells, indicating that this human receptor can couple to multiple signal
      transduction pathways.

PMID- 7514141
TI  - Surgical video review--total thyroidectomy and unilateral lobectomy.

PMID- 7514142
TI  - Into interferon.

PMID- 7514140
TI  - Calcium currents recorded from a neuronal alpha 1C L-type calcium channel in
      Xenopus oocytes.
AB  - Xenopus oocytes expressing neuronal alpha 1C, alpha 2 and beta 1b calcium channel
      subunit cDNAs were used in this study. During two-electric voltage clamp
      recording the oocyte was injected with 10-20 nl of a 100 mM BAPTA solution. Under
      these conditions, the endogenous Ca-activated Cl current was completely
      suppressed resulting in an alpha 1C Ba current free from Cl current
      contamination. BAPTA injection also allowed alpha 1C currents with different
      permeating ions, including Ca, to be examined. Compared to Ba and Sr, alpha 1C
      whole cell Ca currents were smaller in magnitude and showed kinetic and voltage
      dependent properties more similar to those for L-type Ca currents recorded in
      native cells. That Ca-dependent inactivation occurs in BAPTA-buffered cells
      suggests that the Ca-binding site involved in this type of inactivation is very
      close to the pore of the channel.

PMID- 7514143
TI  - The reverse transcriptase of HIV-1: from enzymology to therapeutic intervention.
AB  - The human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS.
      Replication of this virus requires the activity of a retrovirus encoded RNA
      dependent DNA polymerase, or reverse transcriptase (RT). HIV-1 RT is required for
      the synthesis of the double-stranded proviral DNA from the single-stranded
      retroviral RNA genome. HIV-1 RT has two subunits of 66 kDa and 51 kDa. The 66-kDa
      subunit contains the DNA polymerase and RNase H domains whereas the 51-kDa
      subunit, obtained by proteolytic maturation of the former subunit, has only the
      DNA synthetic activity. Two recently reported crystal structures of HIV-1 RT have
      revealed the very asymmetric structure of this molecule. In addition to providing
      information concerning the mechanism of nucleic acid polymerization, biochemical
      and biophysical studies of this enzyme are providing key insights for the design
      of selective antiviral agents. The multiple activities displayed by reverse
      transcriptase in the replication of the retroviral genome ensure that this enzyme
      will remain at the forefront of antiviral strategies in the fight against AIDS
      and other retrovirus-related pathologies.

PMID- 7514144
TI  - Expression of an heterologous gene activating actinorhodin biosynthesis in
      Streptomyces lividans and Streptomyces coelicolor.
AB  - Production of the blue-pigmented antibiotic actinorhodin resulted in activation
      in the non-producer strain Streptomyces lividans, but not in the natural producer
      strain Streptomyces coelicolor, when transformed with an heterologous activator
      gene from Streptomyces fradiae. The gene encodes a 132 nucleotide-long
      transcript, responsible for the actinorhodin production phenotype, and thought to
      act as a putative antisense RNA, which has been detected in the transformed S.
      lividans cultures by reverse transcription followed by cyclic amplification.

PMID- 7514145
TI  - Elastase gene expression in non-elastase-producing Pseudomonas aeruginosa strains
      using novel shuttle vector systems.
AB  - In order to determine whether non-elastase-producing strains of Pseudomonas
      aeruginosa such as N-10, PA103 and IFO3080 can express foreign elastase genes, we
      introduced elastase genes from P. aeruginosa IFO3455 (elastase-producing) as well
      as from PA103 and N-10 into non-elastase-producing P. aeruginosa strains. Results
      suggested that gene expression, secretion, and precursor processing systems of
      elastase were essentially normal in P. aeruginosa N-10 and IFO3080. Our studies
      using various elastase genes showed that both the elastase structural gene and 5'
      upstream regions of P. aeruginosa PA103 were also normal. This was confirmed by
      the finding that P. aeruginosa N-10 and IFO3080 which carry the PA103 elastase
      gene produced elastase. Several deleted or chimeric genes were constructed using
      the 5'-upstream regions of elastase genes from P. aeruginosa N-10 or PA103 and
      studies of expression revealed that two individual DNA bases seem to be important
      in suppressing P. aeruginosa N-10 elastase gene expression. Possible reasons for
      the lack of elastase expression in these non-elastase-producing strains are
      discussed.

PMID- 7514146
TI  - Ribosome binding site consensus sequence of Lactobacillus delbrueckii subsp.
      lactis bacteriophage LL-H.
AB  - The putative ribosome binding sites preceding 32 of Lactobacillus delbrueckii
      subsp. lactis bacteriophage LL-H genes were compared. A highly conserved
      consensus sequence for the ribosome binding sites of LL-H genes was inferred,
      GAAAGGAG. This study included the characterization of the last nucleotides of the
      3'-end of the 16S rRNA molecule from L. delbrueckii subsp. lactis and its
      comparison to the ribosome binding site consensus sequence.

PMID- 7514147
TI  - O-serogrouping and surface components of Aeromonas hydrophila and Aeromonas
      jandaei pathogenic for eels.
AB  - The relationship between virulence, O-serogroup, and some cell-surface features
      (self-pelleting [SP] and precipitation after boiling [PAB], profile of
      lipopolysaccharides [LPSs] and outer membrane proteins [OMPs]) was investigated
      in strains of the pathogenic species Aeromonas hydrophila and A. jandaei isolated
      from eels. Virulent strains of A. hydrophila reacted mostly with O:19 antiserum,
      and those of A. jandaei reacted with O:4, O:11, O:15 and O:29 antisera (Guinee
      and Jansen system). Regarding the PAB and LPS profiles two groups could be
      distinguished; (i) five PAB+ strains of serotype O:19 that possessed a
      homogeneous O polysaccharide side chain and (ii) thirteen PAB- strains
      antigenically diverse that either exhibited a heterogeneous side chain or were
      side chain deficient. A major 50 kDa protein was only found in the PAB+ strains,
      whereas major OMPs detected in PAB- strains ranged from 33 to 45 kDa irrespective
      of the species. Epizootic eel isolates of A. hydrophila belong to serotype O:19
      and share cell-surface features with the Aeromonas highly virulent for other
      hosts. In contrast, epizootic A. jandaei isolates were antigenically diverse.
      These findings reinforce the importance of an O-serotype as an epidemiological
      marker in motile Aeromonas strains pathogenic for eels.

PMID- 7514148
TI  - Complete nucleotide sequence of plasmid pGB3631, a derivative of the
      Streptococcus agalactiae plasmid pIP501.
AB  - The complete nucleotide (nt) sequence of plasmid pGB3631 (5842 nt), a deletion
      derivative of the Streptococcus agalactiae plasmid pIP501, was determined on both
      strands. Six open reading frames (ORFs) were found. Five ORFs were responsible
      for replication, copy-number control and resistance against MLS antibiotics.

PMID- 7514150
TI  - DCC gene alteration in human endometrial carcinomas.
AB  - The present study was undertaken to define the gene(s) of importance on the long
      arm of chromosome 18 (chromosome 18q) in endometrial carcinomas. We analyzed loss
      of heterozygosity (LOH) at 3 loci on chromosome 18q and DCC gene expression by
      the reverse-transcriptase/polymerase chain reaction (RT-PCR) method. Among 61
      tumors that were informative, 16 (26%), estimated to be a minimum number, showed
      allelic losses at one or more chromosome 18q loci. Deletions in these tumors
      possibly involved the region within or near the chromosome 18q 21.3 band where
      the DCC gene was localized. Moreover, the incidence of altered DCC mRNA
      expression was high in these tumors. Appropriate transcription was lost in 5 of 7
      (71%) carcinoma cell lines in addition to 14 of 28 (50%) surgically resected
      tumors. Histopathological differentiation and clinical stage of disease were not
      related to LOH frequency or to DCC mRNA expression. These results suggest that
      the target for allelic loss on chromosome 18q seen in endometrial carcinomas is
      the DCC gene, and that inactivation of this gene may be critical for the
      development of most endometrial carcinomas.

PMID- 7514149
TI  - Organization and sequence of the HpaII restriction-modification system and
      adjacent genes.
AB  - We report the organization of the HpaII restriction and modification (R-M) system
      from Haemophilus parainfluenzae (recognition sequence: 5'...CCGG...3'), the
      sequence of the gene coding for the HpaII restriction endonuclease, and the
      sequence of the upstream flanking DNA. The HpaII system comprises two genes,
      hpaIIM, coding for the methyltransferase (MTase; 358 amino acids (aa), 40.4 kDa:
      product, Cm5CGG), and hpaIIR, coding for the restriction endonuclease (ENase; 358
      aa, 40.9 kDa: product, C'CGG). The genes are adjacent, they have the same
      orientation, and they occur in the order hpaIIM then hpaIIR. The ENase bears
      little as sequence similarity to the isoschizomeric R.BsuFI and R.MspI ENases.
      Upstream of, and partly overlapping hpaIIM is the coding sequence for a 141-aa
      protein that resembles the very-short-patch-repair endonuclease (Vsr) of
      Escherichia coli. Upstream of that is the coding sequence for a protein that
      resembles valyl-tRNA synthetase (ValS).

PMID- 7514151
TI  - Distinct pattern of HSP72 and monomeric laminin receptor expression in human lung
      cancers infiltrated by gamma/delta T lymphocytes.
AB  - We have previously demonstrated that gamma/delta T lymphocytes may participate in
      the host immune response against lung adenocarcinomas. Here we show that, in
      about one-fourth of human lung cancers, gamma/delta T cells represented a
      significant proportion of freshly isolated tumor-infiltrating lymphocytes.
      Moreover, these cells selectively expand in vitro upon culture in the presence of
      IL-2, thus suggesting a prior activation in vivo. Finally, when we evaluated the
      expression of heat shock proteins and of a panel of tumor-associated antigens in
      lung cancers infiltrated by gamma/delta vs. alpha/beta T cells, we found that the
      former displayed a distinct antigenic pattern, characterized by over-expression
      of HSP72 and of the 67-kDa high-affinity laminin receptor, which might account
      for gamma/delta T-cell recognition.

PMID- 7514152
TI  - Alterations in serum levels of insulin-like growth factors and insulin-like
      growth-factor-binding proteins in patients with colorectal cancer.
AB  - It has been reported that insulin-like growth factor (IGF) II is associated with
      human primary colorectal tumors and colon-carcinoma cell lines. Here, we examine
      alterations in circulating levels of IGFs and IGF binding proteins (IGFBPs) in
      patients with colorectal carcinoma, and compare them to age- and nutrition
      adjusted references. We report (i) an increase in serum IGF-II concentrations
      (about 2-fold), whereas IGF-I concentrations are regarded as normal when aging is
      taken into account; (ii) an apparent increase in serum IGFBP-3 levels when
      compared to those of healthy elderly subjects, IGFBP-3 only being detected in the
      150-kDa IGFBP ternary complex as in normal serum; (iii) abnormally elevated serum
      IGFBP-2 levels taking into account the apparent concentrations of IGFBP-3. This
      simultaneous elevation of IGFBP-3 and IGFBP-2 in the serum of patients with
      colorectal tumors appears to be unique in that it reflects a break in the inverse
      relationship between the serum IGFBP-3 and IGFBP-2 levels that is observed in
      normal and in several physiopathological conditions. Moreover, it enables a
      distinction to be made between 76.5% (13/17) of patients with colorectal
      carcinoma and normal adults, age-related healthy aged and malnourished patients.
      We propose that the disturbed serum IGFBP profile observed in the patients with
      colorectal cancer may be a consequence of oversecretion of IGF-II by the tumor
      cells. The usefulness of IGFs and IGFBPs as potential colorectal tumor-associated
      metabolic markers should be further investigated.

PMID- 7514153
TI  - Cellular and karyotypic characterization of two doxorubicin resistant cell lines
      isolated from the same parental human leukemia cell line.
AB  - Separate mechanisms underlying the multidrug resistant (MDR) phenotype were
      identified in 2 independent approaches to select tumour cells resistant to low
      concentrations of doxorubicin (Dox) from the sensitive T cell leukemia cell line
      CCRF-CEM. The CEM/A7 cell line was selected at an initial concentration of 0.005
      microgram/ml of Dox and maintained at 0.07 microgram/ml. In contrast, the CEM/A5
      line was selected using an initial concentration of 0.01 microgram/ml and
      maintained in Dox at a concentration of 0.05 microgram/ml. P-glycoprotein
      expression was demonstrated in the CEM/A7 line but not the CEM/A5 line.
      Amplification of the mdrI gene was not observed in the CEM/A7 cell line. Both
      cell lines showed cross-resistance to a number of structurally unrelated
      cytotoxic drugs including anthracyclines and etoposide (VP-16), although only the
      CEM/A7 line was cross resistant to Vinca alkaloids. Immunoblots of total cell
      lysates of the CEM/A5 line have revealed almost undetectable levels of
      topoisomerase II alpha and beta in this line. Cytogenetic analyses of both lines
      revealed numerous karyotypic abnormalities which were present in the parental
      cell line as well as both resistant cell lines. The CEM/A7 line also demonstrated
      a duplication of part of the long arm of chromosome 7 which included the region
      containing the mdrI gene, a finding not seen in the parental or CEM/A5 line.
      CEM/A5, however, demonstrated an abnormality of chromosome 7, outside the region
      of the mdrI gene, and it also contained a deletion of the short arm of chromosome
      2. Abnormalities in this latter region of genome have been associated with non-P
      glycoprotein-mediated MDR.

PMID- 7514154
TI  - The lectin Griffonia simplicifolia I-A4 (GS I-A4) specifically recognizes
      terminal alpha-linked N-acetylgalactosaminyl groups and is cytotoxic to the human
      colon cancer cell lines LS174t and SW1116.
AB  - The lectin GS I-A4 binds to terminal alpha-N-acetylgalactosaminyl (GalNAc) groups
      (which include the Tn antigen), but not to the closely related tumor-associated
      epitope, sialylated Tn antigen. The lectin also precipitates asialo OSM, but not
      its native sialylated form. Lectin histochemistry with human colonic tissues
      showed that GS I-A4 specifically stained specimens of colon cancer and colonic
      tissues from individuals with FAP; however, normal colonic tissues from patients
      without colonic disease were rarely stained with this lectin. Glycoconjugates
      bound by GS I-A4 were observed on the surface membranes of 2 human colon cancer
      cell lines, LS174t and SW1116, when fluorescein isothiocyanate (FITC)-conjugated
      GS I-A4 was used. GS I-A4 was toxic to these 2 human colon cancer cell lines in
      monolayer culture. A dose-response study conducted using 10-160 micrograms/ml, of
      GS I-A4 demonstrated significant dose-related toxicity against LS174t and SW1116
      cells. At concentrations > 80 micrograms/ml, > 99% of LS174t and > 90% of SW1116
      cells were killed. Four mM GalNAc specifically inhibited the cytotoxic effect of
      GS I-A4 (p < 0.001), whereas 4mM N-acetylglucosamine (GlcNAc) had no effect. Two
      other lectins that recognize terminal alpha-GalNAc residues, DBA and LBL, were
      significantly less cytotoxic to the colon cancer cells than GS I-A4. In the light
      of these findings, we speculate that GS I-A4 may have potential use as a
      diagnostic agent against colorectal cancer.

PMID- 7514155
TI  - Snow blowing and shoveling in normal and asymptomatic coronary artery diseased
      men.
AB  - We evaluated the oxygen uptake and heart-rate responses to self-paced snow
      blowing and snow shoveling in 10 men with asymptomatic coronary artery disease,
      10 older normal men, and six younger normal men. Mean peak treadmill oxygen
      uptake in the three groups ranged from 26.4 +/- 1.1 to 47.3 +/- 3.9 ml/kg per min
      (P < 0.05). Oxygen uptake during snow blowing did not differ significantly among
      subject groups; values were 17.1 +/- 1.3, 17.7 +/- 1.1, and 17.2 +/- 0.9 ml/kg
      per min in the coronary artery disease, older normal, and younger normal groups,
      respectively. Oxygen uptake with snow shoveling was lower (P < 0.05) in those
      with coronary artery disease (18.4 +/- 1.0 ml/kg per min) than in the normal
      groups. In comparison with snow shoveling, oxygen uptake and heart rate did not
      differ (P = NS) from snow blowing in the coronary artery disease group but were
      lower (P < 0.05) with snow blowing in the two normal groups. The results indicate
      that men with asymptomatic coronary artery disease and relatively good functional
      work capacity perform snow blowing and snow shoveling at similar levels of oxygen
      uptake and heart rate.

PMID- 7514156
TI  - Antiarrhythmic effect of converting enzyme inhibitors in congestive heart
      failure.
AB  - In this study 24-h Holter electrocardiographic recordings were used to measure
      the effects of an angiotensin converting enzyme inhibitor, enalapril given for 4
      weeks, on the frequency of cardiac arrhythmias in 24 patients (14 patients had
      enalapril, 30 patients had placebo) with congestive heart failure (New York Heart
      Association Functional Class 3) receiving maintenance therapy with digoxin and
      furosemide. Although the placebo group had no change in the frequence of
      arrhythmias, enalapril-treated patients showed significant decrease in the
      frequency of premature ventricular complexes couplet, bigemine VPS and
      ventricular tachycardia. Moreover, it was observed that six cases of atrial
      fibrillation returned to sinus rhythm. During enalapril treatment, some patients
      experienced increased serum potassium levels, but there was no change in serum
      digoxin levels. We also observed echocardiographic improvement in left
      ventricular function as well as clinical symptoms of congestive heart failure.
      Finally we observed that there was an antiarrhythmic effect of enalapril in
      congestive heart failure. We thought that the antiarrhythmic effect of enalapril
      in congestive heart failure was probably due to hemodynamic improvement.

PMID- 7514157
TI  - 2,4-Diamino-6-hydroxypyrimidine, an inhibitor of GTP cyclohydrolase I, suppresses
      nitric oxide production by chicken macrophages.
AB  - Biosynthesis of nitric oxide (.NO) from L-arginine by nitric oxide synthase (NOS)
      represents a major cytotoxic effector function of macrophages. It has been shown
      that most mammalian NOS requires tetrahydrobiopterin (BH4) as a cofactor and that
      inhibition of BH4 synthesis results in suppressed .NO production. Chicken L
      arginine metabolism differs from that of mammals in that chickens cannot
      synthesize L-arginine de novo. Therefore, it is important to examine whether
      chicken macrophage .NO synthesis is also BH4-dependent. 2,4-diamino-6
      hydroxypyrimidine (DAHP), a specific inhibitor for GTP cyclohydrolase I (GTP-CH;
      EC 3.5.4.16), the rate-limiting enzyme in de novo pterin synthesis, was used to
      block synthesis of BH4. Both chicken peritoneal macrophages (PECs) and the avian
      MC29 virus-transformed macrophage cell line, HD11, exhibited a dose-dependent
      reduction in .NO production (measured as nitrite accumulation) relative to DAHP
      concentration. Authentic BH4 and a substrate for pterin salvage pathway of BH4
      synthesis, sepiapterin, were both capable of restoring the production of .NO in
      DAHP-treated PECs and HD11 macrophages. These results suggest that chicken
      macrophages require active synthesis of BH4 to produce .NO and that chemicals
      interfering with BH4 synthesis may result in suppressed .NO production and,
      hence, .NO-mediated immune function.

PMID- 7514158
TI  - Substance P and adrenocorticotropic hormone do not affect T-lymphocyte adhesion
      to vascular endothelium or surface expression of adhesion receptors.
AB  - Substance P (SP) and adrenocorticotropic hormone (ACTH) are peptides that have
      been shown to have both neurological and immunological effects. Because of the
      demonstrated effects upon immune function, we examined the effects of these
      peptides on T-lymphocyte adhesion to vascular endothelium and surface adhesion
      receptor expression. Neither the adhesion assays nor the expression assays showed
      any statistically significant effect of SP (10 microM) or ACTH (1 microM) for any
      incubation period used. We conclude that, while SP and ACTH have a variety of
      immunomodulatory effects, direct modulation of T-lymphocyte adhesion to vascular
      endothelium is probably not one of them.

PMID- 7514159
TI  - Protective effects of D-penicillamine and a thiazole derivative, SM-8849, on
      pristane-induced arthritis in mice.
AB  - To evaluate the antiarthritic properties of a novel thiazole derivative, the
      drugs SM-8849, D-penicillamine and indomethacin were administered to pristane
      injected DBA/1 mice. The mice were treated daily with the agents for 32 weeks,
      starting from the day of the pristane injection. Treatment with SM-8849 (50
      mg/kg) resulted in an amelioration of arthritic disease, as assessed by clinical,
      radiographic, and histologic examinations. Similar results were obtained in mice
      treated with 50 mg/kg D-penicillamine, although this disease modifying
      antirheumatic drug was slightly less effective than the same dose of SM-8849. In
      contrast, indomethacin at the maximum tolerated dose of 2 mg/kg did not alter the
      course of the disease. SM-8849 and D-penicillamine were also shown to reduce
      serum levels of rheumatoid factors and the acute-phase reactant, serum amyloid P
      component. Indomethacin failed to affect either parameter. Flow cytometric
      analysis revealed an elevation in the T-cell population that expressed CD44, a
      marker of murine memory T-cells, in spleens from pristane-injected mice. SM-8849,
      but not D-penicillamine, prevented the increase in this cell population. These
      results led us to conclude that pristine-induced arthritis was a useful model for
      the evaluation of antirheumatic agents, in that using this model, we were able to
      distinguish disease modifying antirheumatic drugs from nonsteroidal anti
      inflammatory drugs. Our findings also indicate that SM-8849 shows antiarthritic
      activity, with a unique mechanism of action, differing from that of D
      penicillamine.

PMID- 7514160
TI  - Surgical management of pulmonary atresia with ventricular septal defect and
      multiple aortopulmonary collaterals.
AB  - Pulmonary atresia with ventricular septal defect and multiple aortopulmonary
      collaterals is a form of complex congenital heart disease that is the subject of
      continued controversy. Disagreement exists regarding the appropriateness of
      surgical therapy, the timing of operation, and the optimal techniques for repair
      (1,2). The reason for these differences centers around the diversity of
      morphologic and consequent physiologic forms with which this defect presents. The
      relatively small number of patients and large number of subgroups make meaningful
      comparison between differing treatment strategies difficult. We present here the
      approach to these patients that is currently employed at UCLA Medical Center.

PMID- 7514161
TI  - A monotype of human rotavirus serotype 1 involved in a diarrhea outbreak in a
      pediatric ward.

PMID- 7514162
TI  - Peptide interactions with class I and II MHC encoded molecules.

PMID- 7514163
TI  - Rapid communication: MspI restriction fragment length polymorphism at the swine
      MYF6 locus.

PMID- 7514164
TI  - Anti-human immunodeficiency virus type 1 activities of novel non-nucleoside
      reverse transcriptase inhibitors.

PMID- 7514165
TI  - Interferon-gamma induces tyrosine phosphorylation of interferon-gamma receptor
      and regulated association of protein tyrosine kinases, Jak1 and Jak2, with its
      receptor.
AB  - Interferon-gamma (IFN-gamma) induces the expression of a set of early response
      genes by tyrosine phosphorylation of latent transcription factors such as p91.
      Although the tyrosine kinases, Jak1 and Jak2, have recently been shown to be
      critical for signal transduction by IFN-gamma, evidence is lacking for both
      tyrosine phosphorylation of the IFN-gamma receptor (IFN-gamma R) and the
      interaction between Jak1, Jak2, and the IFN-gamma R. In this report, we show that
      binding of IFN-gamma to HeLa cells initiated a series of events that resulted in
      the extremely rapid (15 s) tyrosine phosphorylation of not only Jak1, Jak2, and
      p91 but also the IFN-gamma R. Coimmunoprecipitation experiments revealed that
      Jak1 was associated with the IFN-gamma R prior to ligand binding, whereas Jak2
      became part of the IFN-gamma R-Jak1 complex immediately after ligand binding.
      H2O2/vanadate treatment of cells for 15 min resulted in only the tyrosine
      phosphorylation of Jak1 and IFN-gamma R. Only after 60 min of this treatment did
      we observe tyrosine phosphorylation of Jak2 and p91 and assembly of the
      transcription factor complex FcRF gamma that binds to the promoter of the fcgr1
      gene. These data suggest that JAK1 associates with the IFN-gamma R prior to
      ligand binding. IFN-gamma treatment of cells results in recruitment of JAK2 into
      the IFN-gamma R-Jak1 complex followed by assembly of the transcription factor
      FcRF gamma complex.

PMID- 7514166
TI  - Okadaic acid, a serine/threonine phosphatase inhibitor, induces tyrosine
      dephosphorylation/inactivation of protein kinase FA/GSK-3 alpha in A431 cells.
AB  - The signal transduction mechanism of protein kinase FA/GSK-3 alpha by tyrosine
      phosphorylation in A431 cells was investigated. Kinase FA/GSK-3 alpha was found
      to exist in a highly tyrosine-phosphorylated/activated state in resting cells but
      could be tyrosine-dephosphorylated and inactivated down to less than 15% of
      control values in a concentration-dependent manner by 50-400 nM okadaic acid (a
      specific inhibitor of protein phosphatase types 1 and 2A), as demonstrated by
      metabolic 32P labeling the cells, followed by immunoprecipitation and two
      dimensional phosphoamino acid analysis and by immunodetection in an anti-kinase
      FA/GSK-3 alpha immunoprecipitate kinase assay. Taken together, the results
      provide initial evidence that serine/threonine phosphatase(s) may play a role
      involved in the modulation of kinase FA/GSK-3 alpha activity in cells, suggesting
      an involvement of serine/threonine dephosphorylation in the modulation of
      tyrosine phosphorylation and activation of protein kinase FA/GSK-3 alpha,
      representing a new mode of signal transduction pathway for the regulation of this
      multisubstrate protein kinase in cells.

PMID- 7514167
TI  - Receptor tyrosine phosphatase beta is expressed in the form of proteoglycan and
      binds to the extracellular matrix protein tenascin.
AB  - The extracellular domain of receptor type protein tyrosine phosphatase beta (RPTP
      beta) exhibits striking sequence similarity with a soluble, rat brain chondroitin
      sulfate proteoglycan (3F8 PG). Immunoprecipitation experiments of cells
      transfected with RPTP beta expression vector and metabolically labeled with
      [35S]sulfate and [35S]methionine indicate that the transmembrane form of RPTP
      beta is indeed a chondroitin sulfate proteoglycan. The 3F8 PG is therefore a
      variant form composed of the entire extracellular domain of RPTP beta probably
      generated by alternative RNA splicing. Previous immunohistochemical studies
      indicated that both RPTP beta and the extracellular matrix protein tenascin are
      localized in similar regions of the central nervous system. We have performed co
      aggregation assays with red and green Co-vaspheres coated with tenascin and 3F8
      PG, respectively, showing that the extracellular domain of RPTP beta (3F8 PG)
      binds specifically to tenascin. The interaction between a receptor tyrosine
      phosphatase and an extracellular matrix protein may have a role in development of
      the mammalian central nervous system.

PMID- 7514168
TI  - Nitric oxide as a messenger molecule for myoblast fusion.
AB  - Nitric oxide (NO) is a messenger molecule of vascular endothelial cells,
      macrophages, and neurons. Here, we demonstrate that the activity of NO synthase
      increases transiently but dramatically in chick embryonic myoblasts that are
      competent for fusion. This activity requires Ca2+, calmodulin, and NADPH. In
      addition, the increase in NO synthase activity coincides with an increase in
      cellular cGMP level. Furthermore, NO generated by treatment with sodium
      nitroprusside induces precocious myoblast fusion, while treatment with NG
      monomethyl-L-arginine, a competitive inhibitor of NO synthase, or methylene blue,
      an inhibitor of guanylate cyclase, delays fusion. These results provide the first
      evidence for a strong association of NO with myoblast fusion.

PMID- 7514169
TI  - Point mutation in the fibroblast growth factor receptor eliminates
      phosphatidylinositol hydrolysis without affecting neuronal differentiation of
      PC12 cells.
AB  - Fibroblast growth factors (FGF) stimulate growth arrest and differentiation in
      rat pheochromocytoma PC12 cells. We examined the role of phosphatidylinositol
      (PI) hydrolysis in FGF-induced differentiation of PC12 cells by exploring the
      biological and biochemical activity of a mutant FGF receptor 1 (flg) defective in
      stimulation of PI hydrolysis. We show that point mutation at Tyr-766 (Y766F) of
      the FGF receptor prevents tyrosine phosphorylation of phospholipase C gamma and
      eliminates acidic FGF (aFGF)-induced stimulation of PI hydrolysis in PC12 cells.
      Treatment of PC12 cells expressing either wild-type or the Y766F mutant with aFGF
      led to tyrosine phosphorylation of Shc, the association of Shc with GRB2, a shift
      in the electrophoretic mobility of the Ras guanine nucleotide-releasing factor,
      Sos (son of sevenless), and enhancement in mitogen-activated protein kinase
      phosphorylation. Moreover, stimulation with aFGF led to a typical neurite
      outgrowth of PC12 cells expressing either wild-type or the Y766F FGF receptor
      mutant. These experiments indicate that PI hydrolysis is not essential for FGF
      induced neuronal differentiation of PC12 cells. Moreover, the aFGF-induced Ras
      signaling pathway, which is essential for PC12 cell differentiation, is not
      affected by elimination of PI hydrolysis.

PMID- 7514171
TI  - Uncoupling of muscle and blood platelets Ca2+ transport ATPases by heparin.
      Regulation by K+.
AB  - Heparin (1-10 micrograms/ml) inhibits the Ca2+ transport ATPases found in the
      sarcoplasmic reticulum of skeletal muscle, the plasma membrane of red cells, and
      the dense tubular system of blood platelets, but not the (Na+ + K+)-ATPase or the
      mitochondrial F1-ATPase. In the reversal of the Ca2+ pump, heparin uncouples the
      synthesis of ATP from Ca2+ efflux and inhibits the phosphorylation of the
      sarcoplasmic reticulum Ca(2+)-ATPase by Pi, but has no effect the phosphorylation
      by ATP. The effect of heparin on the muscle Ca(2+)-ATPase is abolished by KCl and
      NaCl (100 mM) and to a lesser extent by LiCl. These monovalent cations are not
      effective as antagonists of heparin on the platelet Ca(2+)-ATPase. The effects of
      heparin are antagonized by the polyamines spermine, spermidine, and ruthenium
      red. Unlike KCl, polyamines are equally effective in counteracting the effects of
      heparin in both muscle and platelet Ca(2+)-ATPases. In addition to heparin, the
      Ca(2+)-ATPases of muscle and blood platelets are also inhibited by dextran
      sulfate and fucose-branched chondroitin sulfate. The inhibition promoted by these
      glycosaminoglycans is antagonized by monovalent cations and polyamines in the
      same manner as heparin. Heparan sulfate, chondroitin sulfate, and hyaluronic acid
      have not effect on the Ca(2+)-ATPases studied.

PMID- 7514170
TI  - Nitric oxide inhibits indoleamine 2,3-dioxygenase activity in interferon-gamma
      primed mononuclear phagocytes.
AB  - Indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase are part of the anti
      tumor and antimicrobial activities of mononuclear phagocytes induced by
      interferon-gamma (IFN gamma). As IDO is a heme-containing enzyme and NO, the
      product of nitric oxide synthase-initiated arginine degradation, is a regulator
      of heme enzymes, we investigated whether NO is capable of modulating IDO activity
      in IFN gamma-primed mononuclear phagocytes. Authentic NO gas or the NO-generating
      compound, diethylamine dinitric oxide adduct, dose-dependently inhibited IDO
      activity in cell lysates prepared from IFN gamma-primed human peripheral blood
      mononuclear cells, as assessed by the ascorbate/methylene blue assay for IDO. In
      contrast, neither nitrite nor nitrate affected IDO activity. Exposure of intact
      IFN gamma-primed human peripheral blood mononuclear cells or monocyte-derived
      macrophages to any of the NO-generating compounds, sodium nitroprusside, glyceryl
      trinitrate, S-nitroso-N-acetylpenicillamine, or diethylamine dinitric oxide
      adduct, resulted in inhibition of both the consumption of tryptophan from and
      formation of its metabolite, kynurenine, in the culture medium. The observed
      inhibition of IDO activity was not due to toxicity of the NO generators and was
      abrogated by the co-addition of oxyhemoglobin, an antagonist of NO function.
      Comparable concentrations of nitrite or nitrate did not inhibit IDO activity in
      intact cells. In contrast to human cells, addition of IFN gamma to murine
      macrophages, cultured in complete RPMI 1640 medium, readily induced nitric oxide
      synthase. Others have reported that such treatment does not induce IDO activity
      in these cells. However, induction of IDO activity was observed in murine
      macrophages when the synthesis of reactive nitrogen species was inhibited, by
      using arginine-free medium and/or the nitric oxide synthesis inhibitor, NG
      monomethyl-L-arginine. Together, these results demonstrate that both exogenous
      and endogenous NO inhibit IDO activity and that oxidative arginine and tryptophan
      metabolism in IFN gamma-primed mononuclear phagocytes are functionally related.
      Our study thereby provides an insight into how these cells may regulate some of
      their antimicrobial and anti-tumor activities.

PMID- 7514172
TI  - Requirements of the secondary structures in the primary transcript for multicopy
      single-stranded DNA synthesis by reverse transcriptase from bacterial retron
      Ec107.
AB  - Multicopy single-stranded DNA (msDNA) is produced by bacterial retroelements
      called retrons. It consists of single-stranded DNA that is linked to an internal
      G residue of an RNA molecule by a 2',5'-phosphodiester linkage. It has been
      demonstrated that specific primary sequences, as well as the secondary structures
      immediately downstream of the G residue, are essential for the cDNA priming
      reaction (Shimamoto, T., Hsu, M.-Y., Inouye, S., and Inouye, M. (1993) J. Biol.
      Chem. 268, 2684-2692). We have now examined the requirement of the structures in
      the region corresponding to DNA for msDNA synthesis. The upper stem region
      consisting of 71 bases of msDNA-Ec107 was found not to be essential, and this
      region could be deleted to efficiently produce a truncated msDNA containing only
      a 36-base single-stranded DNA. Various mutations including base replacements,
      deletions, and insertions were constructed in the lower stem region. It was found
      that any mutations resulting in more stable secondary structures caused reduction
      in msDNA synthesis. The results indicated that reverse transcriptase requires a
      loose secondary structure in the template RNA near the cDNA priming site for cDNA
      elongation.

PMID- 7514173
TI  - Glycogen synthase kinase-3 beta is a dual specificity kinase differentially
      regulated by tyrosine and serine/threonine phosphorylation.
AB  - The enzyme glycogen synthase kinase-3 (GSK-3) has been implicated in the control
      of several metabolic enzymes and transcription factors in response to
      extracellular signals. In the past, the enzyme has been considered to be a
      protein Ser/Thr kinase although it was recently reported to contain Tyr(P)
      (Hughes, K., Nikolakaki, E., Plyte, S. E., Totty, N. F., and Woodgett, J. R.
      (1993) EMBO J. 12, 803-808). A cDNA encoding rabbit skeletal muscle GSK-3 beta
      was cloned and expressed in Escherichia coli as an active protein kinase, with
      apparent M(r) 46,000, capable of phosphorylating several known GSK-3 substrates.
      Recombinant GSK-3 beta autophosphorylated on Ser, Thr, and Tyr residues although
      the enzyme already contained Tyr(P) as judged by its recognition by anti-Tyr(P)
      antibodies. The net result of the autophosphorylation was a 3-5-fold reduction in
      enzyme activity. GSK-3 alpha, purified from rabbit muscle, also underwent
      autophosphorylation but only on Ser and Thr residues. In this case, the
      autophosphorylation stabilized the enzyme activity compared with the control
      lacking ATP/Mg2+. Of several phosphatases tested, the lambda-phage phosphatase
      was the most effective in dephosphorylating at Ser and Thr residues but did not
      dephosphorylate at Tyr residues. The action of the lambda-phosphatase caused a
      reactivation of GSK-3 beta to approximately 80% of the starting activity. The
      protein tyrosine phosphatase PTP1B was able to dephosphorylate at Tyr residues
      leading to a reduction in enzyme activity. A truncated form of GSK-3 beta,
      apparent M(r) 40,000, had a significantly higher specific activity, was defective
      in autophosphorylation, and was not inactivated in the autophosphorylation
      reaction. We conclude that GSK-3 beta is a dual specificity protein kinase in the
      same sense as the mitogen-activated protein kinase/ERK family of enzymes.
      Phosphorylation at different residues differentially controls enzyme activity,
      Ser/Thr phosphorylation causing inactivation and Tyr phosphorylation resulting in
      increased activity.

PMID- 7514174
TI  - The cystic fibrosis transmembrane conductance regulator. Nucleotide binding to a
      synthetic peptide segment from the second predicted nucleotide binding fold.
AB  - Previous studies from this laboratory with a 67-amino acid synthetic peptide (P
      67) demonstrated directly that the first predicted nucleotide binding fold of the
      cystic fibrosis transmembrane conductance regulator (CFTR) binds ATP (Thomas,
      P.J, Shenbagamurthi, P., Ysern, S., and Pedersen, P.L. (1991) Science 251, 555
      557). Although mutational analysis within the predicted second nucleotide binding
      fold indicates that this domain may be functionally important also, direct
      evidence for nucleotide binding is lacking. Here, we report the design, chemical
      synthesis, and purification of a 51-amino acid segment (P-51) of the second
      predicted nucleotide binding fold of CFTR and demonstrate that this peptide binds
      ATP. P-51 consists of amino acid residues from glutamic acid 1228 through
      threonine 1278 and contains a motif, GX4GKS, very similar or identical to that
      found in many nucleotide-binding proteins. The freshly dissolved peptide moves
      predominantly as a single species upon molecular sieve chromatography and readily
      binds ATP without eliciting its hydrolysis. P-51 also readily binds the
      fluorescent ATP analogs TNP-ATP (2'(3')-0-(2,4,6-trinitrophenyl)-adenosine-5'
      triphosphate) and TNP-ADP but exhibits much less capacity to bind TNP-AMP. ATP
      displaces TNP-ATP with a Kd (ATP) of 0.46 mM. In the presence of the denaturant
      urea, P-51 loses most of its binding capacity indicating that structure is
      important for binding. Consistent with this conclusion, circular dichroism
      spectroscopy revealed that P-51 has significant secondary structure. Elements of
      such structure calculated from deconvolution of the circular dichroism spectra
      compare favorably with those predicted from the program of Chou, P.Y., and
      Fasman, G.D. (1977) J. Mol. Biol. 115, 135-175. These experiments provide the
      first direct evidence that the second predicted nucleotide binding fold of CFTR
      binds ATP and define a 51-amino acid segment within the approximately 150-amino
      acid fold critical for this function. They also indicate that the beta and gamma
      phosphate groups of ATP may be important for binding and that the 51-amino acid
      region studied is not sufficient to catalyze ATP hydrolysis. Finally, as seven
      different mutations within P-51 are known to cause cystic fibrosis, these studies
      will be important in future efforts to understand the molecular basis of the
      disease.

PMID- 7514175
TI  - Transforming growth factor-beta 1, but not dexamethasone, down-regulates nitric
      oxide synthase mRNA after its induction by interleukin-1 beta in rat smooth
      muscle cells.
AB  - Nitric oxide (NO), which accounts for the biologic properties of endothelium
      derived relaxing factor, is synthesized from L-arginine by nitric-oxide synthase
      (NOS). Two classes of NOS have been identified: a constitutive, calcium-dependent
      isozyme (cNOS) and an inducible, calcium-independent isozyme (iNOS). NO is
      generated after the induction of iNOS by cytokines such as interleukin-1 beta (IL
      1 beta) and tumor necrosis factor-alpha. As a potent vasodilator, NO may have an
      important role in the severe hypotension of septic shock. We investigated whether
      dexamethasone and transforming growth factor-beta 1 (TGF-beta 1) suppress iNOS
      mRNA after its induction by IL-1 beta. We found that IL-1 beta induced iNOS mRNA
      in rat aortic smooth muscle cells (RASMC) in a dose- and time-dependent fashion.
      IL-1 beta promoted a dramatic and prolonged induction of RASMC iNOS mRNA that
      peaked at 48 h. Dexamethasone prevented this induction of iNOS mRNA only when
      given before the addition of IL-1 beta. In contrast, TGF-beta 1 inhibited the
      induction of iNOS mRNA and NO production in RASMC both before and after the
      addition of IL-1 beta. After 24 h of IL-1 beta stimulation, TGF-beta 1 down
      regulated the iNOS mRNA that had been induced during this initial time period. In
      nuclear run-on experiments, we found that the down-regulation of iNOS mRNA by TGF
      beta 1 in RASMC occurred at the transcriptional level. Our observation that TGF
      beta 1 mediates inhibition of RASMC iNOS mRNA after its induction by cytokines
      may be an important insight into the treatment of septic shock.

PMID- 7514176
TI  - Molecular structure of the water channel through aquaporin CHIP. The hourglass
      model.
AB  - Aquaporin channel-forming integral protein (CHIP) is the first characterized
      water channel protein (genome symbol AQP1), but the molecular structure of the
      aqueous pathway through CHIP remains undefined. The two halves of CHIP are
      sequence-related, and each has three bilayer-spanning domains with the motif
      asparagine-proline-alanine (NPA) at residues 76-78 (in cytoplasmic loop B) and
      192-194 (in extracellular loop E). The NPA motifs are oriented 180 degrees to
      each other, and the second NPA is near cysteine 189, the known site where
      mercurials inhibit osmotic water permeability (Pf). When expressed in Xenopus
      oocytes, the double mutant A73C/C189S exhibited high, mercurial-sensitive Pf
      similar to wild-type CHIP. Conservative substitutions of slightly greater mass in
      or near NPA motifs in loop B or loop E in CHIP caused reduced Pf and failure of
      the protein to localize at the plasma membrane. Certain nonfunctional loop E
      mutants complemented the truncation mutant D237Z. Formation of mixed oligomers
      was demonstrated by velocity sedimentation, immunoprecipitation, and analysis of
      dimeric-CHIP polypeptides. Cellular distributions of individual mutants or
      complementing pairs of mutants were verified by plasma membrane isolation and
      confocal microscopy. An hourglass structural model is proposed in which a
      cytoplasmic chamber (loop B) connects within the membrane to an extracellular
      chamber (loop E) forming a single, narrow aqueous pathway through each of the
      CHIP subunits; subunit oligomerization may provide the vertical symmetry
      necessary for residence within the lipid bilayer.

PMID- 7514177
TI  - Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor
      for heregulin.
AB  - The heregulin/neu differentiation factor gene products were purified and cloned
      based on their ability to stimulate the phosphorylation of a 185-kDa protein in
      human breast carcinoma cell lines known to express erbB2. However, not all cells
      that express erbB2 respond to heregulin, indicating that other components besides
      erbB2 may be required for heregulin binding. Cells that are transfected with the
      closely related receptor, erbB3, display a single class of lower affinity
      heregulin binding sites than has been previously observed on breast carcinoma
      cell lines. Little or no stimulation of tyrosine phosphorylation in response to
      heregulin occurs in cells that are transfected with erbB3 alone. Transfection of
      cells with erbB3 and erbB2 reconstitutes a higher affinity binding receptor,
      which is also capable of generating a tyrosine phosphorylation signal in response
      to heregulin. A monoclonal antibody to erbB2 will inhibit heregulin activation of
      tyrosine phosphorylation and binding in cells transfected with both receptors but
      not with erbB3 alone. In cells expressing erbB2 and erbB3, both proteins become
      tyrosine-phosphorylated upon interaction with heregulin. Direct interaction
      between heregulin and the two proteins was demonstrated by chemical cross-linking
      experiments using 125I-heregulin followed by immunoprecipitation with antibodies
      specific for erbB2 or erbB3.

PMID- 7514178
TI  - Comparison of deoxyoligonucleotide and tRNA(Lys-3) as primers in an endogenous
      human immunodeficiency virus-1 in vitro reverse transcription/template-switching
      reaction.
AB  - We developed an endogenous in vitro reverse transcription assay to study the
      properties of priming and template switching during human immunodeficiency virus
      (HIV) replication. Reactions were primed with HIV reverse transcriptase (RT) and
      either a deoxyoligonucleotide primer (dPR) or tRNA(Lys-3), the natural primer for
      reverse transcription. The RNA templates utilized were the actual HIV sequences
      involved in the first template switch, namely a primer binding sequence
      (PBS)/U5/R RNA donor template and a R/U3 RNA acceptor template. Reverse
      transcription reactions using the latter templates and dPR or tRNA(Lys-3) as
      primers yielded four major products: (-)-strong-stop DNA, a partial template
      switched DNA, full template-switched DNA, and a pseudo-PBS-primed product. Use of
      dPR resulted in three times less template switching than was obtained with
      tRNA(Lys-3). When reactions were primed with either dPR or tRNA(Lys-3), increases
      in acceptor:donor template ratios resulted in augmented template switching.
      Increasing the concentration of RT resulted in increased priming from the PBS but
      had no effect on the efficiency of template switching. Decreasing the extent of R
      region overlap resulted in a drop in efficiency of template switching. Decreases
      in the R region on the donor template also caused a drop in initiation of
      transcription that was primed by tRNA(Lys-3) from the PBS. In contrast, a
      corresponding reduction of the R region on the acceptor template had no effect on
      priming. We conclude that a transcriptional complex of tRNA(Lys-3) and RT may be
      associated not only with the PBS but also with other cis RNA sequences and
      secondary structures in a manner essential for efficient priming and template
      switching.

PMID- 7514180
TI  - Insertional mutagenesis as a probe of rhodopsin's topography, stability, and
      activity.
AB  - This paper reports a study of rhodopsin's structure and function using
      insertional mutagenesis with a flexible epitope. Sixteen rhodopsin derivatives
      were constructed, each of which carried a 12-amino acid epitope derived from the
      c-Myc protein flanked by penta-glycine linkers. For eight of the insertion
      mutants, the membrane sideness of the epitope insert was determined by
      immunostaining of intact or permeabilized cells. The results confirm the
      sidedness of each of the six helix connecting loops and the amino and carboxyl
      termini as postulated by the current seven-helix models of G-protein-coupled
      receptors and provide the first experimental evidence for the existence of the
      third extracellular loop. In general, inserts that were either closer to the
      amino terminus or on the extracellular face were more likely to disrupt folding
      and/or stability than were inserts near the carboxyl terminus or on the cytosolic
      face. Epitope insertion at positions 139 or 239, in the second and third
      cytosolic loops, respectively, failed to activate transducin, whereas an
      insertion at position 333 in the carboxyl-terminal tail was fully functional. The
      experimental approach described here should prove generally useful for
      elucidating structural and functional properties of both membrane and globular
      proteins.

PMID- 7514179
TI  - Rapid anterograde axonal transport of the cellular prion glycoprotein in the
      peripheral and central nervous systems.
AB  - In prion diseases, the cellular prion protein (PrPc), abundant in neurons, is
      converted posttranslationally into an amyloid-forming scrapie prion protein
      (PrPSc), which accumulates in white matter tracts and nerve terminals. The
      trafficking of PrPc in neurons was investigated in vivo by injecting
      [35S]methionine into the L4 and L5 dorsal root ganglia and the entorhinal
      cortices of adult rats and by tracing the movement of radiolabeled PrPc. In both
      paradigms, labeled 33-35-kDa PrPc was transported, within 4 h, to distal axons
      and nerve terminals cofractionating with proteins in the fast component. Future
      studies using these methods may allow us to determine whether PrPc is converted
      into PrpSc during axonal transport and whether PrPSc is transported in animals
      with prion diseases.

PMID- 7514181
TI  - Tyrosine phosphorylation of pp125FAK in platelets requires coordinated signaling
      through integrin and agonist receptors.
AB  - FAK is a focal adhesion kinase that is phosphorylated on tyrosine in activated
      platelets. Induction of FAK phosphorylation requires both fibrinogen binding to
      integrin alpha IIb beta 3 and post-occupancy events during agonist-induced
      platelet aggregation or platelet spreading on a fibrinogen matrix. To identify
      the signaling pathways necessary for tyrosine phosphorylation of FAK, we have
      examined the conditions that stimulate or inhibit this phosphorylation in
      platelets in which fibrinogen binding to alpha IIb beta 3 and platelet
      aggregation were induced directly with an anti-beta 3 Fab fragment (anti-LIBS6).
      Apyrase was added to prevent effects of the endogenous platelet agonist, ADP.
      Under these conditions, neither fibrinogen binding nor primary platelet
      aggregation was sufficient to induce FAK phosphorylation, suggesting that a
      second "costimulatory" event was required. Indeed, when epinephrine was added
      with fibrinogen and anti-LIBS6, large platelet aggregates formed and FAK
      phosphorylation occurred. This response was prevented by blockade of
      cyclooxygenase with indomethacin or thromboxane A2 receptors with SQ 30,741. A
      stable thromboxane A2 analogue (U46619) could substitute for epinephrine as the
      costimulus. Epinephrine costimulation of FAK phosphorylation was also prevented
      by chelation of intracellular Ca2+ with BAPTA or selective inhibition of protein
      kinase C (PKC) with bisindolylmaleimide, indicating that Ca2+ and PKC are
      necessary for FAK phosphorylation under these conditions. Epinephrine also
      promoted FAK phosphorylation and adhesive spreading of apyrase-treated platelets
      on a fibrinogen matrix. Cytochalasin D, an inhibitor of actin polymerization,
      blocked FAK phosphorylation under all these conditions. Thus, tyrosine
      phosphorylation of FAK in platelets requires coordinated signaling through
      occupied integrin and agonist receptors. These separate pathways may converge to
      increase free Ca2+ and activate PKC and thus promote the cytoskeletal
      reorganization required for activation of FAK.

PMID- 7514182
TI  - Reversible cellular adhesion to vitronectin linked to urokinase receptor
      occupancy.
AB  - Urokinase receptors are distributed on surfaces of many cell types where they are
      thought to focus plasminogen-dependent proteolysis important to migration and
      tissue remodeling to the immediate pericellular space. In addition to its well
      characterized role in proteolysis, urokinase receptor binding per se promotes the
      adhesiveness of leukemic cell lines exposed to differentiating cytokines in
      vitro. We sought to determine if a serum or matrix component is involved in
      urokinase-dependent adhesion. We now report that cytokine-stimulated human
      myelomonocytic cells express a divalent cation- and Arg-Gly-Asp-independent high
      affinity receptor for urea-purified vitronectin (Kd < 10 nM). Soluble native
      vitronectin does not effectively bind to the receptor, while cellular adhesion
      was noted to both urea-purified and native vitronectin when adsorbed to plastic.
      The activity of this receptor is tightly coupled to urokinase receptor occupancy.
      Urokinase receptor binding thus induces selective and reversible cellular
      adhesion to the matrix form of vitronectin. Because transfer of vitronectin-bound
      plasminogen activator inhibitor type 1 to urokinase promotes rapid turnover of
      receptor-bound enzyme, these results illuminate a novel binding cycle by which
      urokinase receptor occupancy coordinately regulates cellular adhesiveness and
      pericellular proteolysis.

PMID- 7514183
TI  - [Prophylaxis of deep vein thrombosis in orthopedic surgery. Discussion and review
      of the literature].

PMID- 7514184
TI  - Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in
      experimental allergic encephalomyelitis.
AB  - Anti-tumor necrosis factor (TNF) antibodies inhibit passively transferred
      experimental allergic encephalomyelitis (EAE) in SJL mice. The possibility that
      this occurs through interference in TNF's upregulation of endothelial cell
      adhesion molecules was investigated. Expression of both vascular cell adhesion
      molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on spinal cord
      vessels increased during EAE. The upregulation of VCAM-1 was markedly reduced or
      prevented by anti-TNF treatment. Leukocytic infiltration was 15-fold lower in
      anti-TNF-treated than diseased animals. Spinal cord endothelial expression of
      VCAM-1, though not ICAM-1 or fibronectin, positively correlated with the extent
      of T cell, B cell or monocyte infiltration in each animal.

PMID- 7514185
TI  - Beta-endorphin concentrations in brain areas and peritoneal macrophages in rats
      susceptible and resistant to experimental allergic encephalomyelitis: a possible
      relationship between tumor necrosis factor alpha and opioids in the disease.
AB  - Since the central nervous system and neuropeptides modulate immune functions, we
      investigated whether the different susceptibility of Lewis and Brown Norway rats
      to experimental allergic encephalomyelitis could also reflect differences in beta
      endorphin and substance P concentrations in brain areas and macrophages during
      the development of the disease. We show that beta-endorphin concentrations
      increase much more in the hypothalamus and macrophages of Lewis rats during the
      development of the disease, while the increase is much lower or absent in Brown
      Norway rats. Tumor necrosis factor-alpha seems to play an important role in this
      difference. The administration of the opiate receptor antagonist naltrexone
      worsens the development of the disease, suggesting that the increase of the
      opioid beta-endorphin might represent a mechanism to downregulate the immune
      response. In both strains, the concentrations of substance P do not change.

PMID- 7514186
TI  - Cell adhesion molecules on vessels during inflammation in the mouse central
      nervous system.
AB  - The expression of endothelial cell adhesion molecules (CAMs) in the central
      nervous system (CNS) of the mouse was examined during an inflammation induced by
      intracerebral injection of killed Corynebacterium parvum (C. parvum). We showed
      that injection of killed C. parvum produced an inflammatory cellular infiltrate
      limited to the injected brain hemisphere. However, the upregulation of ICAM-1 and
      VCAM-1 on brain endothelium occurred starting 2 days after C. parvum injection
      throughout the entire CNS and was not restricted to vessels surrounded by a
      cellular infiltrate. In contrast to the systemic upregulation of ICAM-1 and VCAM
      1, cerebral vessels located in the center of the cellular infiltrate started to
      express the MECA-32 antigen, suggesting an altered functional status of the
      endothelial cells, as this antigen is suppressed during development of the blood
      brain barrier (BBB). Binding assays performed on frozen sections of inflamed
      brains are consistent with an important role for endothelial VCAM-1 in the
      recruitment of lymphocytes during inflammation in the CNS of the mouse.

PMID- 7514187
TI  - Nitric oxide and biopterin: a study in Chiaroscuro.

PMID- 7514188
TI  - Permselectivity in thin membrane nephropathy.
AB  - The glomerular permselectivity to polydisperse neutral dextrans was compared in 6
      patients with thin membrane nephropathy (TMN) and 10 healthy controls. Despite
      having normal renal hemodynamics and minimal proteinuria, the patients with TMN
      had significantly increased fractional clearance of neutral molecules with Stokes
      radius > 42 A. Conventional theories of glomerular barrier size selectivity
      cannot fully explain these data since they would predict that our patients would
      have had nephrotic range proteinuria.

PMID- 7514189
TI  - Endogenous nitric oxide enhances prostaglandin production in a model of renal
      inflammation.
AB  - The interaction between nitric oxide (NO) and cyclooxygenase (COX) was studied in
      a rabbit model of renal inflammation, the ureteral obstructed hydronephrotic
      kidney (HNK). Ex vivo perfusion of the HNK but not the control kidney (e.g.,
      unobstructed contralateral kidney, CLK), led to a time-dependent release of
      nitrite (NO2-), a breakdown product of NO. Stimulation of the HNK with bradykinin
      (BK) evoked a time-dependent increase in prostaglandin E2 (PGE2) production. NG
      monomethyl-L-arginine (L-NMMA), which blocks the activity of both constitutive
      and inducible nitric oxide synthase (cNOS and iNOS), aminoguanidine, a recently
      described selective iNOS inhibitor, dexamethasone, or cycloheximide abolished the
      release of NO2- and attenuated the exaggerated BK-induced PGE2 production. This
      supports the existence of iNOS and COX-2 in the HNK. In the CLK, BK elicited
      release of both NO2- and PGE2 but this did not augment with time. L-NMMA but not
      aminoguanidine, dexamethasone, or cycloheximide attenuated NO2- and PGE2 release
      indicative of the presence of constitutive but not inducible NOS or COX. The
      current study suggests that the endogenous release of NO from cNOS in the CLK
      activates a constitutive COX resulting in optimal PGE2 release by BK. In
      addition, in the HNK, NO release from iNOS activates the induced COX resulting in
      markedly increased release of proinflammatory prostaglandin. The broader
      implication of this study is that the cyclooxygenase isozymes are potential
      receptor targets for nitric oxide.

PMID- 7514190
TI  - Cytokines suppress human islet function irrespective of their effects on nitric
      oxide generation.
AB  - Cytokines have been proposed as inducers of beta-cell damage in human insulin
      dependent diabetes mellitus via the generation of nitric oxide (NO). This concept
      is mostly based on data obtained in rodent pancreatic islets using heterologous
      cytokine preparations. The present study examined whether exposure of human
      pancreatic islets to different cytokines induces NO and impairs beta-cell
      function. Islets from 30 human pancreata were exposed for 6-144 h to the
      following human recombinant cytokines, alone or in combination: IFN-gamma (1,000
      U/ml), TNF-alpha (1,000 U/ml), IL-6 (25 U/ml), and IL-1 beta (50 U/ml). After 48
      h, none of the cytokines alone increased islet nitrite production, but IFN-gamma
      induced a 20% decrease in glucose-induced insulin release. Combinations of
      cytokines, notably IL-1 beta plus IFN-gamma plus TNF-alpha, induced increased
      expression of inducible NO synthase mRNA after 6 h and resulted in a fivefold
      increase in medium nitrite accumulation after 48 h. These cytokines did not
      impair glucose metabolism or insulin release in response to 16.7 mM glucose, but
      there was an 80% decrease in islet insulin content. An exposure of 144 h to IL-1
      beta plus IFN-gamma plus TNF-alpha increased NO production and decreased both
      glucose-induced insulin release and insulin content. Inhibitors of NO generation,
      aminoguanidine or NG-nitro-L-arginine, blocked this cytokine-induced NO
      generation, but did not prevent the suppressive effect of IL-1 beta plus IFN
      gamma plus TNF-alpha on insulin release and content. In conclusion, isolated
      human islets are more resistant to the suppressive effects of cytokines and NO
      than isolated rodent islets. Moreover, the present study suggests that NO is not
      the major mediator of cytokine effects on human islets.

PMID- 7514191
TI  - Somatostatin analogues suppress the inflammatory reaction in vivo.
AB  - Somatostatin (Sms) and its agonist analogues inhibit the secretory activities of
      endocrine and neural cells. Recent studies have suggested that Sms has
      significant immunomodulatory properties. In this study, we examine the effects of
      two Sms octapeptide analogues on the inflammatory reaction in vivo. BIM 23014
      (Somatulin) and Sandostatin were administered to male Sprague-Dawley rats subject
      to carrageenin-induced aseptic inflammation, at doses of 2-10 micrograms/rat,
      given either systemically or locally. Animals were killed 7 h after the induction
      of the inflammation, and the inflammatory exudates were aspirated and quantitated
      in terms of volume and leukocyte concentration. Sms analogues, administered via
      either route, significantly reduced the volume and the leukocyte concentration of
      the exudate in a time- and dose-dependent fashion. In corroboration of these,
      immunohistochemical evaluation of the levels of local inflammatory mediators,
      such as immunoreactive (Ir) TNF-alpha, Irsubstance P, and Ircorticotropin
      releasing hormone, was inhibited significantly by Sms analogue treatment. These
      findings suggest that Sms analogues have significant antiinflammatory effects in
      vivo, associated with suppression of proinflammatory cytokines and neuropeptides.
      Furthermore, these data suggest that Sms agonists may be useful in the control of
      inflammatory reaction.

PMID- 7514192
TI  - Evidence that the V kappa III gene usage is nonstochastic in both adult and
      newborn peripheral B cells and that peripheral CD5+ adult B cells are
      oligoclonal.
AB  - There is evidence that in certain situations the expressed antibody repertoire is
      dominated by small subsets of V gene segments. They include fetal, CD5+, and
      autoantibody-forming B cells as well as low grade B cell malignancies. For
      instance, inside the V kappa III family of approximately 10 members, only 3
      (humkv325, 328, and Vg) are used recurrently for autoantibody production.
      However, the significance of this recurrence is difficult to interpret without a
      clear vision of the actual repertoire in normal subjects. To address this, we
      have sequenced and compared two sets of rearranged V kappa III genes generated by
      cDNA PCR amplification from a normal newborn, a normal adult, and from CD5+ B
      cells of the same adult donor. The results show that: (a) only four V kappa III
      gene segments are used by neonatal and total adult B cells (humkv325, humkv328,
      Vg, and kv305), humkv325 being overexpressed in both repertoires; (b) there is no
      significant difference in terms of V kappa III gene usage between the adult and
      newborn repertoires; (c) regarding the junction regions, there is a favored use
      of the most 5' JK gene segments (Jk1-Jk2); approximately 20% of the newborn and
      adult junction sequences was characterized by one or two additional codons, most
      probably resulting from a nontemplate addition of nucleotides; (d) adult clones,
      in contrast to most newborn clones, show sequence divergences from prototype
      sequences with patterns which suggest antigen-driven diversity; (e) regarding the
      adult CD5+ B cell library, it is most probable that the 78 clones analyzed
      derived from no more than nine different VK-JK rearrangements. Humkv325 is used
      by at least six of them, and most of the expressed V genes were in exact or very
      near germline configuration. Collectively these results suggest that the
      expressed antibody V kappa III repertoire in the adult represents only a fraction
      of the potential genetic information and that it resembles the preimmune
      repertoire of the neonate. The data, which also suggest that the adult peripheral
      blood CD5+ B cell population may be dominated by a small number of B cell clones,
      are discussed with regards to the V kappa III usage in pathological situations.

PMID- 7514194
TI  - In vivo proteolysis of serum insulin-like growth factor (IGF) binding protein-3
      results in increased availability of IGF to target cells.
AB  - IGF Binding Protein-3 (IGFBP-3), the major IGF carrier in the blood, undergoes
      limited proteolysis which reduces its affinity for IGFs, thus facilitating
      dissociation. The functional effects of this at the cellular level were studied
      by comparing two serum pools, one from healthy adults, one from women during late
      pregnancy when IGFBP-3 proteolysis is increased. Sera were mixed to yield
      identical IGF-I and IGF-II concentrations in the two pools. Western ligand and
      immunoblotting gave the characteristic IGFBP patterns for the two types of serum.
      Both pools dose-dependently stimulated DNA synthesis in cultured chick embryo
      fibroblasts. Stimulation by pregnancy serum was twice that by normal serum at
      0.05-0.2% concentrations (P < 0.001). In the presence of excess monoclonal anti
      IGF-I and -II antibodies, stimulation by both (0.1-0.2%) pools was 70-80% reduced
      and residual stimulation was similar. Addition of recombinant human (rh) IGFBP-3
      dose-dependently depressed both pools' activity, more so for normal serum at 25
      and 50 ng/ml, equally for each at 100 ng/ml. At the latter concentration, slight
      proteolysis of the rhIGFBP-3 was detectable in the presence of 0.2% pregnancy
      serum, but at 25 ng/ml, proteolysis was absent. These results suggest that IGFs
      are released more readily from pregnancy serum, accounting for the weaker
      inhibitory effect of low rhIGFBP-3 concentrations. For identical IGF
      concentrations, pregnancy serum's greater biological activity therefore reflects
      greater IGF availability to the cells. This study demonstrates the functional
      consequences at cellular level of serum IGFBP-3 proteolysis, underlining its
      significance in regulating serum IGF bioavailability.

PMID- 7514193
TI  - Regulation of nitric oxide synthesis by proinflammatory cytokines in human
      umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels
      enhance endothelial nitric oxide synthase specific activity.
AB  - We have examined cytokine regulation of nitric oxide synthase (NOS) in human
      umbilical vein endothelial cells (HUVEC). 24-h treatment with IFN-gamma (200
      U/ml) plus TNF (200 U/ml) or IL-1 beta (5 U/ml) increased NOS activity in HUVEC
      lysates, measured as conversion of [14C]L-arginine to [14C]L-citrulline.
      Essentially, all NOS activity in these cells was calcium dependent and membrane
      associated. Histamine-induced nitric oxide release, measured by
      chemiluminescence, was greater in cytokine-treated cells than in control cells.
      Paradoxically, steady-state mRNA levels of endothelial NOS fell by 94 +/- 2.0%
      after cytokine treatment. Supplementation of HUVEC lysates with exogenous
      tetrahydrobiopterin (3 microM) greatly increased total NOS activity, and under
      these assay conditions, cytokine treatment decreased maximal NOS activity. IFN
      gamma plus TNF or IL-1 beta increased endogenous tetrahydrobiopterin levels and
      GTP cyclohydrolase I activity, the rate-limiting enzyme of tetrahydrobiopterin
      synthesis. Intracellular tetrahydrobiopterin levels were higher in freshly
      isolated HUVEC than in cultured cells, but were still limiting. We conclude that
      inflammatory cytokines increase NOS activity in cultured human endothelial cells
      by increasing tetrahydrobiopterin levels in the face of falling total enzyme;
      similar regulation appears possible in vivo.

PMID- 7514196
TI  - Overlapping T-cell epitopes in the group I allergen of Dermatophagoides species
      restricted by HLA-DP and HLA-DR class II molecules.
AB  - The induction of IgE antibodies reactive with the group I allergen of
      Dermatophagoides species (house dust mite [HDM]), which comprise a major
      component of the allergic immune response in HDM-atopic individuals, is dependent
      on the functional activity of specific CD4+ T cells. In this report we
      demonstrate that for a particular HDM-atopic individual the T-cell response to
      the group I allergen of Dermatophagoides pteronyssinus (Der p I) is limited to a
      single region (residues 101-143) of the protein. By mapping the fine antigen
      specificity with T-cell clones, we observed that the sequence 101-131 of Der p I
      contains a cluster of at least three overlapping T-cell epitopes. Analysis of the
      HLA class II restriction specificity of the T-cell clones revealed that the T
      cell epitope, residues 110-131, was restricted by HLA-DRB1*0101. In contrast,
      peptide Der p I, 110-119 was recognized in association with HLA-DPB1*0402.
      However, the ability of cloned T cells to proliferate to the peptide Der p I, 107
      119 presented by HLA-DPB1*0401, HLA-DPB1*0402, and HLA-DPB1*0501 expressing
      accessory cells illustrates the heterogeneity of the restriction specificity of
      this region of Der p I. The application of this information in the design of
      peptide-based immunotherapy in the management of allergic responses to HDM is
      discussed.

PMID- 7514195
TI  - Cardiac preservation is enhanced in a heterotopic rat transplant model by
      supplementing the nitric oxide pathway.
AB  - Nitric oxide (NO) is a novel biologic messenger with diverse effects but its role
      in organ transplantation remains poorly understood. Using a porphyrinic
      microsensor, the first direct measurements of coronary vascular and endocardial
      NO production were made. NO was measured directly in the effluent of preserved,
      heterotopically transplanted rat hearts stimulated with L-arginine and
      bradykinin; NO concentrations fell from 2.1 +/- 0.4 microM for freshly explanted
      hearts to 0.7 +/- 0.2 and 0.2 +/- 0.08 microM for hearts preserved for 19 and 38
      h, respectively. NO levels were increased by SOD, suggesting a role for
      superoxide-mediated destruction of NO. Consistent with these data, addition of
      the NO donor nitroglycerin (NTG) to a balanced salt preservation solution
      enhanced graft survival in a time- and dose-dependent manner, with 92% of hearts
      supplemented with NTG surviving 12 h of preservation versus only 17% in its
      absence. NTG similarly enhanced preservation of hearts stored in University of
      Wisconsin solution, the clinical standard for preservation. Other stimulators of
      the NO pathway, including nitroprusside, L-arginine, or 8-bromoguanosine 3',5'
      monophosphate, also enhanced graft survival, whereas the competitive NO synthase
      antagonist NG-monomethyl-L-arginine was associated with poor preservation. Likely
      mechanisms whereby supplementation of the NO pathway enhanced preservation
      included increased blood flow to the reperfused graft and decreased graft
      leukostasis. NO was also measured in endothelial cells subjected to
      hypoxia/reoxygenation and detected based on its ability to inhibit thrombin
      mediated platelet aggregation and serotonin release. NO became undetectable in
      endothelial cells exposed to hypoxia followed by reoxygenation and was restored
      to normoxic levels on addition of SOD. These studies suggest that the NO pathway
      fails during preservation/transplantation because of formation of oxygen free
      radicals during reperfusion, which quench available NO. Augmentation of NO/cGMP
      dependent mechanisms enhances vascular function after ischemia and reperfusion
      and provides a new strategy for transplantation of vascular organs.

PMID- 7514197
TI  - Eosinophil granule proteins inhibit substance P-induced histamine release from
      human skin mast cells.
AB  - We have investigated the activity of the four principal cationic proteins of the
      eosinophil granules, major basic protein (MBP), eosinophil peroxidase (EPO),
      eosinophil-derived neurotoxin, and eosinophil cationic protein on histamine
      release from human skin mast cells. These four cationic proteins, over the
      concentration range of 10 to 200 micrograms/ml, did not induce significant
      histamine release, nor did they prime anti-IgE-induced histamine release from
      human skin mast cells significantly. However, a brief incubation (15 minutes) of
      two of the four principal eosinophil granule proteins, MBP and EPO, at
      concentrations of 50 to 200 micrograms/ml, caused a significant concentration
      related inhibition of histamine release induced by 30 mumol/L substance P. The
      concentrations producing 50% inhibition for MBP and EPO on substance P-induced
      histamine release were 30 micrograms/ml and 100 micrograms/ml, respectively. This
      inhibitory effect appears to be a direct effect of these proteins on skin mast
      cells because purified (78% to 85%) skin mast cells displayed a similar response
      to MBP and EPO (n = 4). Also, when skin mast cells were incubated with 100
      micrograms/ml MBP and EPO for 15 minutes and washed twice before activation by
      substance P, the inhibitory effect was not altered. These two proteins also
      inhibited histamine release induced by 10 micrograms/ml compound 48/80. These
      results suggest that MBP and EPO affect the same binding site(s) on skin mast
      cells as those of substance.

PMID- 7514198
TI  - Enhanced repair endonuclease activities from radiation-arrested G2 phase
      mammalian cells.
AB  - HeLa cells arrested in G2 phase 22 h after receiving 11.5 Gy gamma-radiation
      contained 3.6-fold more EDTA-resistant DNA repair endonuclease activity than
      unirradiated cells. Enzyme activity was determined by measuring the release of
      fragments from an irradiated repetitive alpha DNA substrate or from synthetic
      substrates containing a single modified base, 8-oxoguanine (8-oxo-G), a major
      radiation product. It appeared that the radiation-induced enhanced repair
      activity in some cells might be a feature of radiation-induced G2 arrest. Indeed,
      unirradiated G2 HeLa cells that had been synchronized by double thymidine block
      contained 3-7-fold more endonuclease activity than G1 or S-phase cells.
      Similarly, two of four other cell lines tested exhibited elevated repair
      endonuclease activity in G2. However, all six cell lines tested exhibited
      radiation-enhanced repair endonuclease activity. Therefore, the underlying
      mechanism for radiation enhancement of enzyme activity remains to be clarified
      and does not seem to be completely accounted for as a consequence of G2 arrest.
      The results showed different substrate specificities among cell lines as well as
      differences during the cell cycle of individual cell lines. Repair endonuclease
      activity from all cell lines which we have tested were associated with 60-70 kDa
      proteins from Superose 12 columns. Since reports from other laboratories have
      described several different DNA repair activities in 50-70 kDa Superose 12
      fractions, it seems possible that the DNA repair enzymes may be associated in a
      repairosome structure.

PMID- 7514199
TI  - Serotonin-stimulated aortic endothelial cells secrete a novel T lymphocyte
      chemotactic and growth factor.
AB  - Atherosclerotic lesions contain multiple cell types including smooth muscle
      cells, macrophages, and T lymphocytes. The development of an extralymphatic T
      lymphocyte focus of inflammation in this condition requires chemoattractant
      induced cell migration and growth factor-induced cell activation. In a previous
      study, we described a novel 13-15-kDa T lymphocyte-specific chemotactic cytokine,
      endothelial cell-derived lymphocyte chemoattractant activity (ED-LCA), secreted
      by serotonin-stimulated bovine aortic endothelial cells that is distinct from
      previously identified endothelial cell-derived interleukins (IL) 1, 6, and 8.
      Because of the association between T lymphocyte chemotactic and growth factor
      activity, in the current study we investigated the effect of ED-LCA on T cell
      growth. We assessed its capacity to induce markers of the passage of T cells from
      the resting (G0) state into the G1 phase of the cell cycle, such as receptors for
      IL-2 (IL-2R) and transferrin (TFR) and class II major histocompatibility complex
      antigens (HLA-DR). Incubation of G0 freshly isolated human T lymphocytes for 48 h
      with chromatographically resolved, partially purified ED-LCA resulted in a
      threefold increase in expression of the p55 subunit of IL-2R, a threefold
      increase in TFR, and a twofold increase in HLA-DR. Passage into the G1 phase of
      the cell cycle was confirmed by cell cycle analysis employing acridine orange.
      Evaluation of CD4+ and CD8+ T cell subsets by double-antibody labeling
      demonstrated that the p55 subunit of IL-2R was induced in both T cell subsets.
      Although incubation of human T cells with ED-LCA alone did not induce
      proliferation, addition of exogenous IL-2 to T cells pulsed with ED-LCA for 24 h
      caused a proliferative response with a stimulation index of 3. By up-regulating
      functional cell surface receptors for IL-2, ED-LCA is a competence growth factor
      for T lymphocytes and primes them to respond to IL-2. By virtue of its effect on
      T cells, as a chemotactic and competence factor, this endothelial cell-derived
      mitoattractant could participate with other T cell growth factors like IL-2 in
      the recruitment and amplification of the extralymphatic T cell component of
      atherosclerosis.

PMID- 7514200
TI  - Differential expression of mast cell growth factor receptor (c-kit) by peritoneal
      connective tissue-type mast cells and tissue culture-derived mast cells.
AB  - The peritoneal cavity of the mouse is a major source of connective tissue-type
      mast cells (CTMCs). Flow cytometric analysis using biotinylated recombinant
      murine mast cell growth factor (rMuMGF) showed that 1 to 3% of the cells in the
      peritoneal cavity exhibited MGF receptor (MGFR) (or c-kit). CTMCs were the only
      cell types expressing MGFR in the peritoneal cavity, and every one of them
      expressed MGFR. More than half the peritoneal CTMCs retained the potential to
      proliferate in the presence of recombinant murine interleukin 3 (rMuIL-3), rMuIL
      4, and rMuMGF and gave rise to pure, alcian blue-positive "mast cells," which
      actively expressed c-kit transcripts and MGFR. Flow cytometric analysis and
      receptor assay carried out at 4 degrees C showed that the number of MGFRs on
      culture-derived mast cells (CDMCs) was one-third that of peritoneal CTMCs (6 x
      10(4) vs. 1.8 x 10(5) MGFR/cell). At 37 degrees C, the total number of membrane
      MGFRs detected in CDMC was two to three times more than that detected at 4
      degrees C, indicating that nearly 70% of total MGFR in CDMCs, compared with only
      40% in peritoneal CTMCs, existed as "cryptic sites" unable to interact with
      exogenous ligand at 4 degrees C. Thus, diminished expression of MGFR is one of
      the phenotypic characteristics associated with CDMCs.

PMID- 7514201
TI  - The role of G-CSF in mature neutrophil function is not related to GM-CSF-type
      cell priming.
AB  - Because of uncertainties regarding the comparability of granulocyte-macrophage
      and granulocyte colony-stimulating factors with regard to their effects on mature
      neutrophils (PMNs), we compared the actions of the two cytokines on reactive
      oxidant production and granular secretion by these cells. We found that
      chemiluminescence (CL) stimulated by formylmethionyl-leucyl-phenylalanine (fMLP)
      was not influenced by G-CSF (0.1-100 ng/ml), whereas GM-CSF priming (10 ng/ml)
      caused a nearly twofold increase in this PMN response. Moreover, the reactivity
      of PMNs treated with GM-CSF and G-CSF in combination was not different from that
      of PMNs treated with GM-CSF alone. GM-CSF (10 ng/ml) increased the rate of O2-
      production by 79%, caused a fivefold increase in fMLP-induced myeloperoxidase
      (MPO) secretion, and strongly enhanced CD11b expression. In contrast, G-CSF (50
      ng/ml) only slightly increased O2- production (by 15%), and MPO secretion and
      CD11b expression remained unchanged. Both cytokines together gave results similar
      to those obtained with GM-CSF alone. In the presence of platelets (which by
      themselves enhanced PMN reactivity), the differences in the effects of the two
      cytokines persisted. We conclude that the priming effect of G-CSF on mature PMNs
      is negligible compared with that of GM-CSF. Our results are in conflict with
      previous reports of much more pronounced G-CSF effects but in accord with recent
      work showing the failure of this cytokine to induce a range of effects produced
      by GM-CSF. We therefore suggest that the primary role of G-CSF in mature PMN
      function is still unclear but may be related to the control of PMN distribution
      in view of the mobilizing and marginating effects of the cytokine in vivo.

PMID- 7514202
TI  - A note on modeling mechano-chemical transduction with an application to a skin
      receptor.
AB  - Strain-sensitive (also called stretch-sensitive) ionic channels are thought to be
      present in various mechanoreceptors. The gating of these channels is precipitated
      by mechanical strains, as opposed to the usual activation processes of changes in
      membrane potential or other ligands. Below we present a class of models for the
      strain-activated mechanism, compare our approach to one of Sachs and Lecar (1991)
      and apply the gating mechanism to a model of a specific mechanoreceptor, namely a
      Pacinian corpuscle neurite model. The simulation experiment suggests the
      activation energy of the channel depends linearly, rather than nonlinearly, on
      the (hoop) strain in the receptor membrane.

PMID- 7514203
TI  - Effect of thyroidectomy, and thyroxine and alpha 2u-globulin replacement therapy
      on testicular steroidogenic and gametogenic activities in rats.
AB  - Adult male rats were thyroidectomized and killed after 22 days of treatment.
      Thyroidectomy lowered the weights of testes and accessory sex organs, decreased
      the activities of testicular delta 5-3 beta- and 17 beta-hydroxysteroid
      dehydrogenases (HSD), and diminished spermatogenesis, serum levels of
      testosterone and alpha 2u-globulin. Supplementation with thyroxine at a dose of 5
      micrograms/100 g body weight per day for 21 days or supplementation with alpha 2u
      globulin at a dose of 1.5 mg/rat per day for 21 days in thyroidectomized animals
      partially reversed the decrease in HSD activities and serum concentrations of
      testosterone and alpha 2u-globulin, while spermatogenesis was restored to normal.
      The weights of testes and accessory sex organs were also reinstated after
      supplementation with thyroxine or alpha 2u-globulin in thyroidectomized rats in
      comparison with thyroidectomized animals. It was concluded that alpha 2u-globulin
      may be an intermediary in the thyroid hormone control of testicular function.

PMID- 7514204
TI  - Differences in the association of insulin-like growth factor-I (IGF-I) and IGF-I
      variants with rat, sheep, pig, human and chicken plasma-binding proteins.
AB  - Associations between labelled insulin-like growth factors (IGFs) and IGF-binding
      proteins in plasma have been compared in the rat, sheep, human, pig and chicken.
      The IGFs tested were recombinant human IGF-I, the truncated variant, des(1-3)IGF
      I, and LR3IGF-I, an extended form that had been engineered so as to minimize
      interactions with IGF-binding proteins. Marked species differences were
      demonstrated, notably that the IGF-I variants which exhibited extremely weak
      binding in rat plasma bound significantly in plasma from the other species. This
      result was shown both by size-exclusion chromatography of labelled IGFs added to
      plasma, in which the extent of variant IGF-I binding decreased in the order sheep
      > human > pig = chicken > rat, and by competition for labelled IGF-I binding in
      vitro, in which the order was pig = chicken > sheep > human > rat.
      Notwithstanding these differences, the two IGF-I variants showed only slight
      between-species binding differences when tested with purified rat, sheep and
      human IGF-binding protein-3. Ligand blotting experiments with plasma from the
      five species similarly showed a consistent pattern in that IGF-I binding was much
      greater than des(1-3)IGF-I binding, which in turn was greater than LR3IGF-I
      binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514205
TI  - Total amounts of circulating human chorionic gonadotrophin alpha and beta
      subunits can be assessed throughout human pregnancy using immunoradiometric
      assays calibrated with the unaltered and thermally dissociated heterodimer.
AB  - The aim of the present study was to determine the variations in the balance
      between total (free plus combined) circulating alpha and beta subunits of human
      chorionic gonadotrophin (hCG) throughout human pregnancy. The equivalence between
      the International Units (IU) of hCG (IRP 75/537) and those assigned to the alpha
      (IRP 75/569) and beta (IRP 75/551) free subunits was experimentally determined by
      using intact and thermally dissociated hCG. Heat exposure (2 min at 100 degrees
      C) of hCG preparations resulted in a complete dissociation of hCG into free,
      soluble and intact alpha and beta subunits. The hCG and alpha and beta subunit
      contents of unaltered and heated hCG preparations were assessed by specific
      immunoradiometric assays. The amount of immunoreactive subunits dissociated by
      heat from hCG could then be evaluated on a molar basis. Circulating hCG and its
      free alpha and beta subunits were immunoassayed in 836 blood samples collected
      from healthy pregnant women at different gestational ages. After conversion of
      hCG and its subunits into a common IU system, the gestational profiles of the
      total amounts (free plus combined) of alpha- and beta hCG subunits increased
      together and peaked at 9-10 weeks of gestation. Thereafter, total alpha and beta
      subunits decreased and subsequently remained stable until term. The decline in
      total alpha hCG subunit was less marked than that of total beta hCG subunit. The
      alpha- to beta hCG ratio was equimolar until 10 weeks of gestation when it
      increased almost fourfold until term (P < 0.0001).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7514207
TI  - Medial lemniscal and spinal projections to the macaque thalamus: an electron
      microscopic study of differing GABAergic circuitry serving thalamic somatosensory
      mechanisms.
AB  - The synaptic relationships formed by medial lemniscal (ML) or spinothalamic tract
      (STT) axon terminals with neurons of the somatosensory ventroposterolateral
      thalamic nucleus of the macaque monkey have been examined quantitatively by
      electron microscopy. ML and STT axons were labeled by the anterograde axon
      transport of WGA-HRP following injection of the tracer into the contralateral
      dorsal column nuclei, or the dorsal horn of the spinal cord, respectively.
      Thalamic tissue was histochemically reacted for the presence of HRP. Serial thin
      sections were stained with a gold-labeled antibody to GABA, to determine which
      neuronal elements exhibited GABA immunoreactivity (GABA-ir). Serially sectioned
      thalamic structures were recorded in electron micrographs and reconstructed in
      three dimensions by computer. Individual ML axon terminals form multiple synaptic
      contacts with segments of the proximal dendritic trees of thalamocortical relay
      neurons and also synapse upon the dendritic appendages of GABA-ir interneurons
      (local circuit neurons). These GABA-ir dendritic appendages contain synaptic
      vesicles and are presynaptic (presynaptic dendrites) to the same segments of
      relay neuron dendrites that receive ML contacts. When analyzed in serial sections
      and reconstructed by computer, the ML terminals form triadic relationships (ML,
      GABA appendage, and relay neuron dendrite) or more complex glomerular
      arrangements involving multiple appendages, all of which then contact the relay
      neuron dendritic segment. In contrast, multiple STT terminals make synaptic
      contacts along segments of projection neuron dendrites and are usually the only
      type of profile to contact that segment of dendrite. More than 85% of the spinal
      afferents form simple axodendritic synapses with relay cells and do not contact
      GABA-ir appendages. The thalamic synaptic relationships of ML terminals are
      fundamentally different from those formed by the STT. Because STT neurons
      predominatly transmit information about noxious stimuli, the simple axodendritic
      circuitry of the majority of these spinal afferents suggests that the
      transmission of noxious information is probably not subject to GABAergic
      modulation by thalamic interneurons, in contrast to the GABAergic processing of
      non-noxious information carried by the ML afferents. The differences in the
      GABAergic circuits of the thalamus that mediate ML and STT afferent information
      are believed to underlie differential somatosensory processing in the forebrain.
      We suggest that changes in thalamic GABAergic dendritic appendages and GABA
      receptors following CNS injury may play a role in the genesis of some central
      pain states.

PMID- 7514206
TI  - Insulin-like growth factor-binding protein-1 is correlated with low density
      lipoprotein cholesterol in normal subjects.
AB  - Insulin-like growth factor-I (IGF-I) has been inversely associated with low
      density lipoprotein (LDL) cholesterol in normal women with slightly elevated
      cholesterol levels and hypothyroid women. More than 95% of IGF-I circulates bound
      to binding proteins (IGFBPs); of these IGFBP-1 is of particular interest as it is
      inversely regulated by insulin and is thought to inhibit the action of IGF-I and
      IGF-II. We examined the relationship between IGFBP-1 and LDL cholesterol in 41
      healthy adult subjects. LDL cholesterol correlated with the body mass index (r =
      0.40, P < 0.01), sex (r = 0.51, P < 0.001) and IGFBP-1 levels (r = 0.36, P <
      0.02). LDL cholesterol did not correlate with age (r = 0.25, P = not significant)
      or IGF-I (r = 0.06, P = not significant). Upon multivariate regression analysis,
      sex, body mass index and IGFBP-1 were all independent predictors of LDL
      cholesterol (all P < 0.05). Elevated IGFBP-1 levels have been associated with an
      inhibition of serum IGF-I bioactivity in children with insulin-dependent
      diabetes. IGFBP-1 also appears to inhibit IGF-I hexose-stimulated uptake. IGFBP-1
      may also be inhibiting the effect of IGFs on the cellular metabolism of LDL
      cholesterol.

PMID- 7514208
TI  - The role of oligodendrocytes and myelin on axon maturation in the developing rat
      retinofugal pathway.
AB  - In neonatal mammals, newly grown optic axons are uniformly small in diameter. In
      the adult, in contrast, axons within the optic nerve can be classified into
      distinct groups according to their diameter. Because axon diameters are also
      related to the thickness of the myelin sheath, which in turn determines the
      velocity of action potential propagation, the question of what determines the
      axon diameter is of critical importance. In a project aimed at determining the
      influence of the ensheathing cell on axon maturation, oligodendrocyte development
      was prevented by eliminating their precursors by unilateral x-irradiation at
      birth. Axon diameters in both the normal and the myelin-free optic nerves were
      then measured at varying stages of development. The results demonstrate that axon
      diameter growth remained substantially reduced in the absence of
      oligodendrocytes. Interestingly, by x-irradiating the optic nerve and tract on
      one side of the brain, fibers crossing the chiasm became larger as they went from
      an unmyelinated nerve to a myelinated tract; fibers on the nonirradiated side
      became smaller as they went from a myelinated nerve and crossed into the
      nonmyelinated tract. These results clearly point to a local regulation of axon
      diameter by oligodendrocytes. Moreover, ganglion cells measured 9 d after the
      initiation of myelination (postnatal day 6, P6) were of similar size within
      normal retinas and retinas whose axons were x-irradiated, suggesting that
      ganglion cell growth occurs in spite of the lack of myelin and axon diameter
      maturation. Finally, we showed, through both section staining with antibodies to
      myelin basic protein (MBP) and Northern blot analysis using a probe to MBP, that
      the x-irradiated nerve began a delayed myelination period (in a gradient from
      chiasm to eye) at P15 and reached an almost normal myelin pattern at P28. Axons
      from these nerves grew to seemingly normal diameter concomitant with this delayed
      myelination.

PMID- 7514209
TI  - Time course of recovery of extracellular dopamine following partial damage to the
      nigrostriatal dopamine system.
AB  - Partial damage to the nigrostriatal dopamine (DA) system can produce severe
      behavioral deficits, from which animals gradually recover. Although the
      compensatory neuroadaptations that contribute to recovery of function have
      received considerable attention, the exact role of presynaptic versus
      postsynaptic contributions remains unclear. For example, it has been suggested
      that presynaptic adaptations may not be sufficient to account for recovery of
      function, because compensatory increases in DA biosynthesis, metabolism, and
      release are maximal within 3 d following a unilateral 6-hydroxydopamine (6-OHDA)
      lesion, before behavioral recovery is complete. The purpose of this study was to
      examine another presynaptic adaptation, the normalization of extracellular DA. If
      this is also complete within 3 d postlesion, it, too, would be insufficient to
      account for the protracted time course of behavioral recovery. But if the
      normalization of extracellular DA proceeds more gradually, it could potentially
      account for the time course behavioral recovery. To address this issue, the
      extracellular concentration of striatal DA ipsilateral and contralateral to a
      unilateral 6-OHDA lesion was estimated with microdialysis, either 4 d or 3-4
      weeks following the lesion. After estimating the basal extracellular
      concentration of DA, the ability to increase DA release further was assessed by
      administering an amphetamine challenge. It was found that in animals with a 6
      OHDA lesion, the concentration of DA in dialysate was higher than would be
      predicted by the extent of DA denervation. Furthermore, in groups matched for
      lesion size, extracellular DA was significantly higher 3-4 weeks following a 6
      OHDA lesion than 4 d following the lesion. These findings suggest that the
      normalization of extracellular DA may be a relatively gradual process, and
      therefore may be sufficient to account for the protracted time course of
      behavioral recovery.

PMID- 7514210
TI  - Functional organization of corticocortical projections from area 17 to area 18 in
      the cat's visual cortex.
AB  - We used anatomical and physiological methods to study the functional organization
      of the association projection from area 17 to area 18 in the cat's visual cortex.
      Neurons in area 17 projecting to area 18 (revealed by retrograde transport of
      fluorescent tracer) tend to be clustered over regions of layer 4 receiving input
      from the ipsilateral eye (visualized by anterograde transneuronal tracing). Since
      the contralateral input overlaps these ipsilateral patches, the association cells
      lie preferentially in regions that are likely to be binocularly innervated.
      Indeed, almost all cells recorded electrophysiologically within the association
      clusters were strongly binocular, whereas between the clusters, many neurons were
      dominated by the contralateral eye. There is sufficient jitter in the retinotopic
      organization of area 17 for the discontinuous distribution of association cells
      to provide a continuous representation of the visual field. Cells in each
      association cluster in the rostral part of area 17 project divergently to
      innervate a zone extending up to 3 mm wide, anteroposteriorly, in the superficial
      layers of area 18. The receptive fields of cells at any point in area 18 are
      larger than for the corresponding point in area 17. Neurons recorded at two
      points in area 18, separated by a distance equal to the limit of anatomical
      divergence of the projection from area 17, have receptive fields that overlap by
      an amount similar to the region of visual field covered by the receptive fields
      of cells in a single association cluster in area 17 at a similar retinotopic
      position. Thus, area 18 receives a full and strongly binocular representation of
      the visual field not only from the lateral geniculate nucleus but also from area
      17. The divergence of the area 17 to 18 projection compensates for the difference
      in receptive field size by ensuring that the receptive fields of each cluster of
      projecting neurons overlap fairly precisely those of the recipient neurons in
      area 18.

PMID- 7514211
TI  - Postnatal development and plasticity of corticocortical projections from area 17
      to area 18 in the cat's visual cortex.
AB  - We used retrogradely transported fluorescent tracers to study the development of
      projections from area 17 to area 18 in normal and monocularly deprived kittens.
      In newborn animals, cells in area 17 that were labeled from small, discrete
      injections in area 18 were concentrated around the retinotopically corresponding
      zone, but distributed with lower density over a very wide surrounding area.
      Hence, the total convergence and divergence of the projection were initially
      enormous, but they decreased dramatically, mainly during the first postnatal
      month, through elimination of the sparse, widespread distribution of projections.
      Injections of two different tracers close together in area 18 produced very few
      double-labeled cells in area 17 at any age, implying that most individual axons
      arborize over very small territories even at birth. In normal kittens the peak
      density of association cells in the upper layers, corrected for the overall
      expansion of the cortex, doubled over the first postnatal month and then declined
      gradually over the following several months, presumably because of continuing
      selection and elimination. As shown in previous work (Price and Blakemore,
      1985a), area 17 to 18 cells in newborn kittens were distributed in two continuous
      bands in supragranular and infragranular layers. During normal maturation,
      elimination of projections results in the formation of distinct clusters; these
      lie preferentially in the upper layers above patches of ipsilateral eye input to
      layer 4 (Price et al., 1994). Monocular deprivation, which causes the terminal
      patches representing the deprived eye to become much smaller than normal, did not
      stop the normal decrease in overall convergence/divergence or the appearance of
      clusters of association cells, but the clusters were distinctly larger than
      normal in both hemispheres. Monocular deprivation also prevented the normal
      reduction in density of association cells within clusters after 1 month of age.
      Comparison with results from binocularly deprived animals, where clusters also
      form but association cell density is low, suggests that the size of clusters and
      the density of association cells retained depend on the overall level of cortical
      activity.

PMID- 7514212
TI  - A novel epitope of entactin is present at the mammalian neuromuscular junction.
AB  - The extracellular matrix (ECM) at the neuromuscular junction (NMJ) is
      biochemically and functionally specialized, and bears molecules that can regulate
      both the formation and function of this peripheral synapse. We have previously
      purified one synaptic component of the muscle ECM--a unique laminin isoform named
      s-laminin--from a rat schwannoma cell line (Chiu et al., 1992). To develop new
      probes for the ECM, monoclonal antibodies were generated against other components
      produced by this cell line. One of these new antibodies, 9H6, binds selectively
      at the synaptic cleft of NMJs in adult rats, but not at extrasynaptic sites on
      the muscle surface. On Western blots, 9H6 recognizes a 150 kDa band that
      colocalizes, and copurifies with the laminin-binding, ECM glycoprotein entactin
      under both reducing and nonreducing conditions. N-terminal sequence analysis also
      indicates that the 9H6 antigen is related to entactin. However, polyclonal
      antibodies to entactin stain both synaptic and extrasynaptic sites. Thus, 9H6
      appears to identify an entactin epitope with a very restricted distribution.
      Treatment with N-glycanase reduces the molecular mass of entactin and eliminates
      9H6 binding, suggesting that the 9H6 epitope at synapses is dependent on
      glycosylation. Recent studies have shown that novel isoforms of laminin, collagen
      IV, agrin, and AChE are selectively sequestered at the NMJ. Our results indicate
      that the entactin present at the synaptic cleft also differs from entactin
      present outside the synapse. The synaptic form of entactin may contribute to the
      unique functions of the ECM at the neuromuscular synapse.

PMID- 7514213
TI  - Distinct populations of sensory neurons mediate the peristaltic reflex elicited
      by muscle stretch and mucosal stimulation.
AB  - Recent studies suggest that muscle stretch and mucosal stimulation elicit
      intestinal peristalsis by activating distinct populations of sensory neurons that
      converge on the same population of enteric motor neurons. The present study
      sought to characterize the origin and projections of these sensory neurons. The
      reflex was elicited by applying muscle stretch and mucosal stroking to the
      central compartment of a three-compartment flat-sheet preparation of rat colon
      while ascending contraction and descending relaxation were measured in the orad
      and caudad compartments, respectively. Identical graded responses were elicited
      by muscle stretch and mucosal stimulation: atropine (1 microM) and the tachykinin
      antagonist spantide (10 microM) inhibited ascending contraction when added to the
      orad compartment only, while the vasoactive intestinal peptide antagonist VIP10
      28 (10 microM) and the NO synthase inhibitor NG-nitro-L-arginine (100 microM)
      inhibited descending relaxation when added to the caudad compartment only.
      Addition of capsaicin (1 microM) to the central compartment for 30 min abolished
      ascending contraction and descending relaxation elicited by muscle stretch and
      mucosal stimulation. Recovery of response was complete when capsaicin was applied
      to the mucosa of the colon in situ and measurements made 1 d after, implying that
      at this low concentration capsaicin depleted sensory nerve terminals of their
      transmitter content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514214
TI  - An animal model of early-treated PKU.
AB  - Phenylketonuria (PKU) is a genetic disorder in which the hydroxylation of
      phenylalanine (Phe) to tyrosine is severely disrupted. If PKU is left untreated,
      severe mental retardation results. The accepted treatment is to restrict dietary
      intake of Phe. It has generally been thought that cognitive impairments are
      prevented if levels of Phe in plasma are maintained at or below five times the
      normal level. However, we recently documented that children treated early and
      continuously for PKU or children mildly hyperphenylalaninemic, who have levels of
      Phe in plasma approximately three to five times normal, still have cognitive
      impairments. These impairments are specific to the functions of frontal cortex
      (A. Diamond, W. Hurwitz, E. Lee, W. Grover, and C. Minarcik, unpublished
      observations). To investigate the mechanism underlying these cognitive deficits,
      an animal model of this condition was developed and characterized. Thirty-six rat
      pups were divided into three groups. The first group was treated pre- and
      postnatally with Phe and alpha-methylphenylalanine (a phenylalanine hydroxylase
      inhibitor). The second group was injected postnatally with Phe and alpha
      methylphenylalanine. The third group received postnatal control injections. The
      mild plasma Phe elevations in the two experimental groups produced significant
      behavioral and neurochemical effects. Both experimental groups were impaired on a
      task dependent on frontal cortex, delayed alternation. Levels of dopamine,
      homovanillic acid (HVA), norepinephrine, and 5-hydroxyindole acetic acid (5-HIAA)
      were measured in medial prefrontal cortex, anterior cingulate cortex, striatum,
      and nucleus accumbens. The largest neurochemical reductions observed were in HVA
      and were in the two frontal cortical areas (medial prefrontal cortex and anterior
      cingulate cortex). There were modest reductions in HVA in the nucleus accumbens
      but no significant changes in HVA, or in any other metabolite or
      neurotransmitter, in the striatum. The levels of 5-HIAA were also reduced in all
      brain regions examined. There was no effect on norepinephrine in any of the four
      regions examined. Reduced levels of HVA in medial prefrontal cortex were the only
      neurochemical effect that significantly correlated with every measure of
      performance on the delayed alternation task. This study provides evidence of
      deleterious effects from mild elevations in the levels of Phe in plasma
      previously considered small enough to be safe. These effects include impaired
      performance on a cognitive task dependent on frontal cortex and reduced HVA
      levels in frontal cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514216
TI  - The NH2-terminus of substance P modulates NMDA-induced activity in the mouse
      spinal cord.
AB  - Excitatory amino acids (EAAs) and substance P are believed to transmit
      nociceptive information in the spinal cord. As substance P NH2-terminal fragments
      can modulate non-NMDA EAA-mediated activity, we examined the effects of substance
      P fragments to ascertain whether the COOH- or NH2-terminus of substance P
      modulates the actions of NMDA in the spinal cord. NMDA activity was measured by
      the intensity of behaviors produced by NMDA (0.2 nmol) administered intrathecally
      in the mouse. The NMDA response was attenuated after pretreatment with either
      substance P (22.5 pmol, 30 min) or the NH2-terminal fragment of substance P, SP
      (1-7). Pretreatment with the COOH-terminal fragment SP-(5-11) (22.5 pmol, 30
      min), a neurokinin ligand, had no effect on NMDA-induced behaviors, suggesting
      that the inhibitory effect of substance P is caused by the NH2-terminus.
      Pretreatment with D-Pro2,D-Phe7 substance P-(1-7), a SP-(1-7) antagonist,
      potentiated NMDA activity, suggesting a tonic inhibitory effect of the substance
      P NH2-terminus. Desensitization to NMDA typically develops when NMDA is injected
      at 2 min intervals. While pretreatment with SP-(1-7) inhibited NMDA,
      coadministration of SP-(1-7) (22.5 pmol), with the first of four injections of
      NMDA, first inhibited but then potentiated responses to each challenge with NMDA.
      Coadministration of the same dose of SP-(1-7) with the fourth injection of NMDA
      immediately potentiated the response to NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514215
TI  - The minK potassium channel exists in functional and nonfunctional forms when
      expressed in the plasma membrane of Xenopus oocytes.
AB  - The minK protein induces a slowly activating voltage-dependent potassium current
      when expressed in Xenopus oocytes. In order to measure the levels of minK protein
      in the plasma membrane, we have modified the minK gene by inserting a 9 amino
      acid epitope into the N-terminal domain of the protein sequence. When intact live
      oocytes are injected with the modified minK RNA and subsequently incubated with
      an antibody to this epitope, specific binding is detected, indicating that the N
      terminal domain is extracellular. We found that when oocytes are injected with
      amounts of minK mRNA up to 50 ng, the levels of protein at the surface are
      proportional to the amount of injected mRNA. In contrast, the amplitude of the
      minK current recorded in the oocytes saturates at 1 ng of injected mRNA. Although
      the amplitude of the currents is not altered by increasing mRNA levels above 1
      ng, the kinetics of activation of the current differ in oocytes with high or low
      levels of minK RNA. In particular, activation is slower with higher levels of
      minK protein in the plasma membrane. Finally, we find that increasing
      intracellular cAMP levels, which increases the amplitude of minK currents, does
      not alter surface expression of the minK protein but produces a small increase in
      the rate of activation of the current. Our results support a model in which minK
      protein forms functional potassium channels by association with a factor
      endogenous to the oocyte.

PMID- 7514217
TI  - Signaling by insulin-like growth factors in paralyzed skeletal muscle: rapid
      induction of IGF1 expression in muscle fibers and prevention of interstitial cell
      proliferation by IGF-BP5 and IGF-BP4.
AB  - In the absence of muscle activity, muscle fibers, muscle interstitial cells, and
      intramuscular nerves display characteristic reactions presumably aimed at
      restoring a functioning neuromuscular system and avoiding degenerative events. In
      partially denervated muscle these include proliferation of interstitial cells,
      followed by nerve sprouting. The same reactions can be induced in intact muscle
      by elevation of intramuscular insulin-like growth factor (IGF) levels. To
      determine whether IGFs may participate in the initiation of restorative reactions
      in inactivated muscle we analyzed the expression of IGF1 and IGF2 mRNA in
      botulinum toxin-paralyzed and in denervated rat skeletal muscle, and interfered
      with the activity of IGFs by locally applying the IGF-binding proteins IGF-BP5
      and IGF-BP4. To obtain a resolution of the in situ hybridization signals at the
      cellular level, a nonradioactive method based on digoxigenin-labeled probes was
      applied. We found that muscle fiber IGF1 mRNA increased rapidly and transiently
      in inactivated muscle. The time course of this response was similar to that
      reported for ACh receptor subunits and myogenins. A similar behavior was observed
      for the corresponding IGF1 protein. The IGF1 response coincided with the
      transient muscle interstitial cell proliferation reaction. Local application of
      recombinant IGF-BP5 or IGF-BP4, which are endogenous and specific extracellular
      ligands of IGFs, prevented the stimulation of interstitial cell proliferation in
      paralyzed muscle. Our data demonstrate the elevated production of the growth
      factor IGF1 among early reactions in electrically inactive skeletal muscle fibers
      and indicate that muscle IGFs are required for the induction of intramuscular
      interstitial cell proliferation. These findings support the hypothesis that in
      the neuromuscular system IGF1 plays an important role in initiating cellular
      reactions in the vicinity of inactive muscle fibers.

PMID- 7514218
TI  - The medical/surgical nurse program. A flexible response to the changing patient
      care environment.
AB  - The medical/surgical nurse program at Stanford University Hospital was designed
      to provide patient care units with clinical professional support to manage
      emergency or other unpredictable situations in a challenging healthcare
      environment. As a result of this program, staff members have access to clinical
      nursing experts who provide valuable support to improve patient care services in
      the most cost-effective manner.

PMID- 7514220
TI  - Many agents that antagonize the NMDA receptor-channel complex in vivo also cause
      disturbances of motor coordination.
AB  - Antagonists of the NMDA receptor-channel complex may be useful for the treatment
      of thrombotic stroke, head injury and epilepsy. Their clinical use, however,
      could be limited by the incidence of side effects such as ataxia. I have
      therefore investigated the relationship between functional antagonism of the N
      methyl-D-aspartate (NMDA) receptor-channel complex in vivo and disturbances of
      motor coordination. Antagonism of the NMDA receptor-channel complex was assessed
      by measuring a compounds ability to inhibit NMDA-induced lethality in mice,
      disturbances of motor coordination were measured by the rotarod technique. NMDA
      dose-dependently induced convulsions and ultimately caused death in mice (LD50 =
      137 +/- 4 mg/kg i.p.). Noncompetitive NMDA antagonists of either an
      arylcyclohexylamine (phencyclidine, (+)/(-)-MK-801 [10-11-dihydro-5-methyl-5H
      dibenzo[a,d] cyclohepten-5,10-imine hydrogen maleate] and ketamine) or a
      benzomorphan (dextrorphan and N-allylnormetazocine) structure, competitive
      antagonists (CGP 37849 [(R,S)-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid
      monohydrate] and CGP 39551 [(R,S)-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic
      acid 1-ethyl ester]) or a glycine site antagonist (L-687,414 [(3R,4R)-3-amino-4
      methyl-1-hydroxy-pyrrolidin-2-one-(-)-tartrate salt]) inhibited NMDA-induced
      lethality after s.c. administration. These compounds also interfered with motor
      coordination. There was an excellent correlation (r = 0.97) between the two
      effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514219
TI  - The effects of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, on
      norepinephrine overflow and antidiuresis induced by stimulation of renal nerves
      in anesthetized dogs.
AB  - We examined the involvement of endogenous nitric oxide (NO) in noradrenergic
      neurotransmission and renal function in anesthetized dogs, by using NG-nitro-L
      arginine (NOARG), a NO synthase inhibitor. Renal nerve stimulation (RNS) produced
      the frequency-dependent increase in the rate of norepinephrine secretion. The low
      frequency RNS (0.5-2.0 Hz) decreased urine flow and urinary excretion of sodium,
      without affecting renal hemodynamics. High frequency RNS (2.5-5.0 Hz) caused a
      more potent antidiuresis and renal vasoconstriction that resulted in reductions
      in renal blood flow and glomerular filtration rate. Intrarenal arterial infusion
      of NOARG, at a dose (10 micrograms/kg/min) which had no effect on renal
      hemodynamics, significantly enhanced the RNS-induced reductions of urine
      formation and renal vasoconstriction and increments in norepinephrine secretion
      rate. Qualitatively similar results were observed with a higher dose of NOARG (40
      micrograms/kg/min), although this dose did decrease basal levels of renal blood
      flow and urine flow. Enhancement of NOARG on RNS-induced actions was abolished by
      the simultaneous administration of L-arginine. Endogenous NO probably has a role
      as inhibitory modulator of renal noradrenergic neurotransmission.

PMID- 7514221
TI  - Tonic regulation of mouse ileal ion transport by nitric oxide.
AB  - The possible role of nitric oxide (NO) in the regulation of intestinal ion
      transport was studied in isolated sheets of mouse ileum mounted in Ussing flux
      chambers. The competitive NO-synthase inhibitors NG-methyl-L-arginine (L-NMA),
      and NG-nitro-L-arginine (L-NNA) and the effects of NO released from acidified
      sodium nitrite solution were evaluated in tissues pretreated with guanethidine
      and atropine. Serosal L-NMA or L-NNA (10-300 microM), but not NG-methyl-D
      arginine (D-NMA), produced a sustained concentration-related increase in short
      circuit current (Isc) and potential difference (PD) with maximal Isc increases of
      50.8 +/- 8.2 and 45.5 +/- 5.8 microAmps/cm2, respectively; mucosal application of
      L-NMA or L-NNA produced transient increases in Isc. The A50 (and 95% CL) values
      for serosal L-NMA and L-NNA were 25.6 (15.7-41.9) and 8.7 (5.1-14.9) microM,
      respectively. L-Arginine (0.1-10 mM), but not D-arginine, produced both a
      concentration-related reversal of L-NMA or L-NNA-induced increases in Isc.
      Additionally, pretreatment with L-arginine blocked the L-NMA or L-NNA effects,
      suggesting a competitive interaction. L-NMA-mediated increases in Isc were
      unaffected by bicarbonate-free buffer, whereas replacement of chloride ions with
      gluconate ions almost completely attenuated the response to L-NMA. Further, the
      effects of L-NMA or L-NNA were blocked by tetrodotoxin or chlorisondamine,
      suggesting neural actions involving ganglionic transmission.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7514223
TI  - Dexfenfluramine and serotonin neurotoxicity: further preclinical evidence that
      clinical caution is indicated.
AB  - Dexfenfluramine, a drug used as an appetite suppressant in Europe, is currently
      under evaluation for approval in the United States. Studies in animals indicate
      that dexfenfluramine damages brain serotonin neurons, but have been challenged by
      some because of questions regarding their relevance to humans. The present
      studies were designed to address the three most salient questions regarding the
      applicability of preclinical dexfenfluramine neurotoxicity data to humans.
      Specifically, the present studies sought to determine: 1) whether
      dexfenfluramine's effects on brain serotonin neurons are transient and related to
      its therapeutic actions; 2) whether the p.o. route of administration affords
      protection against dexfenfluramine neurotoxicity; and 3) whether the mouse, an
      animal thought to best approximate the human with regard to dexfenfluramine
      metabolism, is sensitive to dexfenfluramine's neurotoxic action. Results from the
      present study indicate that monkeys continue to show large serotonergic deficits
      as long as 12 to 17 months after dexfenfluramine treatment, suggesting that
      dexfenfluramine's effects in nonhuman primates are persistent and unlikely to be
      related to its therapeutic actions. Furthermore, the present results indicate
      that the p.o. route of administration affords little or no protection against
      dexfenfluramine neurotoxicity. Finally, mice, like all other animals tested to
      date, were found to be susceptible to dexfenfluramine neurotoxicity. Taken
      together, these findings indicate that concern over possible dexfenfluramine
      neurotoxicity in humans is warranted, and that physicians and patients alike need
      to be aware of dexfenfluramine's toxic potential toward brain serotonin neurons.

PMID- 7514222
TI  - Pharmacological evidence that nitric oxide mediates the antinociception produced
      by muscarinic agonists in the rostral ventral medulla of rats.
AB  - The present study was designed to characterize the antinociception produced by
      the administration of a muscarinic agonist, (+)-cis-methyldioxolane, into the
      rostral ventral medulla (RVM) of male Sprague-Dawley rats. Seven days after the
      implantation of 25-gauge stainless-steel guide cannulae, animals were injected
      with graded doses of (+)-cis-methyldioxolane, and antinociception was assessed by
      using the 52 degrees C hot-plate and tail-flick tests in a single-blind design.
      (+)-cis-Methyldioxolane produced dose-related hot-plate and tail-flick
      antinociception for 30 to 45 min peaking 5 to 10 min after RVM injection. The
      ED50 values of (+)-cis-methyldioxolane in the hot-plate and tail-flick tests were
      2.4 and 1.7 nmol, respectively. Five-minute preinjections with 0.35 nmol of the
      muscarinic M1 receptor blocker pirenzepine competitively antagonized the
      antinociception produced by (+)-cis-methyldioxolane. The antinociception produced
      by RVM injections of the muscarinic M2 receptor blocker methoctramine was
      additive to the antinociceptive effects of (+)-cis-methyldioxolane when the two
      antinociceptive effects of (+)-cis-methyldioxolane when the two agents were
      combined. Twenty four-hour pretreatment of the RVM with the irreversible
      muscarinic receptor antagonist 4-diphenylacetoxy-N-[2-chloroethyl]-piperidine
      mustard blocked the antinociceptive effects of (+)-cis-methyldioxolane
      completely. Administration of 6 nmol of the nitric oxide synthase inhibitor L-NG
      nitroarginine into the RVM competitively antagonized the antinociception produced
      by (+)-cis-methyldioxolane and (+)-muscarine in the hot-plate and tail-flick
      tests. Pretreatment with 100 nmol of L-arginine, but not D-arginine,
      significantly reversed the inhibitory effects of L-NG-nitroarginine on (+)-cis
      methyldioxolane-produced antinociception. Pretreatment with 100 nmol of the
      guanylyl cyclase inhibitor methylene blue into the RVM profoundly antagonized the
      antinociception produced by (+)-cis-methyldioxolane. Neither buffer L-NG
      nitroarginine, L-arginine-D-arginine or methylene blue altered hot-plate or tail
      flick nociception when injected alone into the RVM. In contrast, either dibutyryl
      cyclic GMP or 8-bromo cyclic GMP, membrane-permeable cyclic GMP analogs, produced
      hot-plate and tail-flick antinociception when injected alone into the RVM. These
      data are consistent with the hypothesis that the antinociception produced by
      muscarinic stimulation of the RVM is mediated by an L-arginine/nitric
      oxide/cyclic GMP cascade.

PMID- 7514224
TI  - Neurohormone D induces ionic current changes in cockroach central neurones.
AB  - The octapeptide neurohormone D (NHD), a member of the family of adipokinetic
      hormones (AKH-peptides), increases the frequency of spontaneous activity in
      dorsal unpaired median (DUM) neurones isolated from the terminal ganglion of the
      cockroach Periplaneta americana. The increase in spike frequency is accompanied
      by changes in the shape and the amplitude of the single action potentials, e.g. a
      more pronounced afterhyperpolarization. Effects of NHD on membrane currents were
      investigated in these DUM cells with whole-cell voltage-clamp measurements. A
      voltage-independent Ca2+ current flowing at the resting potential (ICa,R) was
      found. NHD, at nanomolar concentrations, enhanced this ICa,R in a concentration
      dependent manner. 0.1 mM Cd2+ markedly reduced ICa,R and in this case ICa,R was
      hardly potentiated by NHD. In the presence of NHD a fast activating Ca(2+)
      dependent K+ current sensitive to charybdotoxin and to low concentrations of
      tetraethylammonium was augmented. The enhanced afterhyperpolarization of action
      potentials can be accounted for by the increase in the Ca(2+)-dependent K+
      current. The changes of the membrane currents induced by NHD are discussed with
      respect to further effects on the spike pattern and in relation to the previously
      described mode of action of AKH-peptides in other preparations.

PMID- 7514225
TI  - Evidence of hepatitis C virus antibodies in the cryoprecipitate of patients with
      mixed cryoglobulinemia.
AB  - OBJECTIVE: To describe the clinical features of 8 patients with mixed
      cryoglobulinemia and hepatitis C virus (HCV) infection. METHODS: A clinical study
      of the patients was performed. Anti-HCV antibodies were determined by ELISA and
      confirmed by immunoblot (RIBA) in the sera and in the cryoprecipitate. RESULTS:
      All patients had liver dysfunction, while most had arthralgias and/or arthritis,
      purpura, peripheral nervous system involvement and renal disorders. Cryocrits
      ranged from 1 to 6%. Six patients had type III mixed cryoglobulinemia and the
      remaining 2 had type II. History of blood transfusion was recorded in 2 patients.
      Hepatitis B virus (HBV) markers were negative in all sera samples. The
      cryoprecipitate of 7 patients was negative for HBV markers, but anti-HCV
      antibodies were positive by both ELISA and RIBA. CONCLUSION: After reviewing
      published reports and discussing the possible role that hepatitis C virus plays
      in the pathogenesis of mixed cryoglobulinemia, we conclude that HCV may stimulate
      immune complex formation and produce cryoglobulinemia. Therefore its
      investigation is recommended before the diagnosis of "essential" mixed
      cryoglobulinemia is established.

PMID- 7514226
TI  - Intermittent loading induces the expression of 3-B-3(-) epitope in cultured
      bovine articular cartilage.
AB  - OBJECTIVE: To study the effects of intermittent loading on the proteoglycans
      synthesized in intact cultured articular cartilage. METHODS: Sesamoid bones
      carrying articular cartilage were subjected to cyclic loading in vitro for one
      week. A new procedure to fix and decalcify the tissue was developed and an
      immunohistochemical analysis of the expression of 3-B-3(-) epitope in the
      articular cartilage was carried out. The proteoglycans synthesized were
      quantified and studied using CL-2B chromatography. RESULTS: Loading induced an
      increase in the synthesis of aggrecan molecules, which were larger and less
      polydisperse than those from control cartilage. Loading also induced the
      expression of 3-B-3(-) epitopes on newly synthesized proteoglycans. CONCLUSION:
      These changes are similar to those found in early experimental and human
      osteoarthritis (OA). More variables must be studied, but our results suggest that
      our model might be suitable to study early events in the onset of OA.

PMID- 7514227
TI  - Association of 1078 del T cystic fibrosis mutation with severe disease.
AB  - Apart from the high frequency of the delta F508 mutation (81.81%) in Breton
      cystic fibrosis chromosomes, one mutation, 1078 del T, is also observed
      frequently (4.96%) in this group, in comparison with the rest of the French where
      it occurs with a frequency of 0.57%. These two mutations account for more than
      86.5% of the total CF mutations identified on Breton chromosomes. We have
      conducted an unblinded retrospective analysis of 25 patients with the 1078 del T
      mutation and compared their phenotypes with those of a group of 70 delta F508
      homozygous patients. Both groups of patients had the same ethnic origin and were
      regularly attending the same CF centre in Brittany, which makes this sample
      highly homogeneous despite the small size. The 1078 del T mutation appeared to be
      associated with severe presentation of the disease with, however, a trend to
      reduced mortality and less Pseudomonas aeruginosa colonisation.

PMID- 7514228
TI  - Osmotic flow in membrane pores of molecular size.
AB  - Water transfer by osmosis through pores occurs either by viscous flow or
      diffusion depending on whether the driving osmolyte is able to enter the pore.
      Analysis of osmotic permeabilities (Pos) measured in antibiotic and cellular pore
      systems supports this distinction, showing that Pos approaches either the viscous
      value (Pf) or the diffusive value (Pd) depending on the size of the osmolyte in
      relation to the pore radius. Macroscopic hydrodynamics and diffusion theory, when
      used with drag and steric coefficients within an appropriate osmotic model, apply
      with remarkable accuracy to channels of molecular dimensions where water
      molecules cannot pass each other, without the need to postulate any special flow
      regimens. It becomes apparent that the true viscous to diffusive flow ratio,
      Pf/Pd, can be separated from the effects of tracer filing by osmotic measurements
      alone. It does not monotonically decrease with the pore radius but rises steeply
      at the smaller radii which would apply to pores in cell membranes. Consequently,
      the application of the theory to osmotic and diffusive flow data for the red cell
      predicts a pore radius of 0.2 nm in agreement with other recent measurements on
      isolated components of the system, showing that the viscous-diffusive distinction
      applies even in molecular pores.

PMID- 7514230
TI  - Requirement of 3'-terminal guanosine in (-)-stranded RNA for in vitro replication
      of cucumber mosaic virus satellite RNA by viral RNA-dependent RNA polymerase.
AB  - The 3' terminus of the (-) RNA strand in the replicative forms of several (+)
      stranded RNA viruses possesses an unpaired guanosine with unknown function. This
      unpaired guanosine is also found at the 3' terminus of the (-) strand in the
      double-stranded form of two cucumoviral satellite RNAs. Using a cucumber mosaic
      virus (CMV) RNA-dependent RNA polymerase capable of replicating the satellite RNA
      in vitro, the 3'-terminal guanosine of the satellite (-) strand was shown to be
      an absolute requirement for satellite (+) strand synthesis. If genomic RNA
      synthesis of CMV and other members of the alphavirus-like superfamily that
      produce (-) strands terminating in an unpaired 3' guanosine follows a similar
      strategy, the work reported here would represent the first experimental support
      for the notion of 3'-terminal guanosine functioning as an essential recognition
      signal for viral replicases, enabling (+) strand RNA synthesis to be initiated
      internally from a (-) strand template.

PMID- 7514229
TI  - Characterization of ion channels in the plasma membrane of epidermal cells of
      expanding pea (Pisum sativum arg) leaves.
AB  - Ion channels in isolated patches of the plasma membrane of pea (Pisum sativum
      arg) epidermal cells were studied with the patch-clamp technique. One anion and
      one cation channel were dominantly present in most trials. The anion channel
      conducts nitrate, halides and malate, with a conductance in symmetrical 100 mM Cl
      of 300 pS and can be blocked by SITS when applied to the cytoplasmic side of the
      membrane. The cation channel poorly discriminates between potassium, sodium and
      lithium, is not blocked by either TEA or Ba2+, and has a conductance of 35 pS in
      symmetrical 100 mM K+. The open probability of the cation channel increases with
      increase of the Ca2+ concentration on the cytoplasmic side of the membrane from
      0.1 to 1 microM. The possible role of these two channels in the physiology of
      epidermal cells is discussed.

PMID- 7514231
TI  - Breast-feeding and HIV--a balance of risks.
AB  - HIV-1 infection may be transmitted by breast-feeding. The risk of vertical
      transmission varies with the stage of maternal infection, but is 29 per cent if a
      mother acquires infection during lactation. The risk of infant death by not
      breast-feeding in a poor and contaminated environment is greater than the risk of
      HIV-infection when an HIV-positive mother breast-feeds. Vertical transmission can
      be reduced if women avoid high risk activities during pregnancy and especially
      lactation.

PMID- 7514232
TI  - [Ventricular arrhythmia during cesarean section due to intramyometrically
      administered prostaglandin F2 alpha: report of two cases].
AB  - Case 1 was a healthy 28 year old woman. Spinal anesthesia was performed for
      Cesarean section. After the delivery, prostaglandin F2 alpha (PGF2 alpha) 1000
      micrograms was administered intramyometrically. Immediately ventricular premature
      beats appeared on ECG and heart rate decreased to 60.min-1. Atropine sulfate 0.25
      mg was administered and ECG showed sinus tachycardia. Case 2 was a 28 year old
      healthy woman. Spinal anesthesia was induced for Cesarean section. PGF2 alpha
      1000 micrograms was injected to the myometrium. Soon thereafter blood pressure
      rose to 170/105 mmHg and ECG showed multifocal ventricular premature beats.
      Lidocaine 40 mg and nicardipine hydrochloride 0.4 mg were administered. Blood
      pressure decreased to 120/80 mmHg and ECG showed sinus tachycardia. These cases
      demonstrate the systemic reaction of intramyometrically administered PGF2 alpha.

PMID- 7514233
TI  - [The practical knowledge of the nurses in the palliative care unit].

PMID- 7514235
TI  - The role of exercise testing in heart failure.
AB  - The objectives of exercise testing in congestive heart failure (CHF) may be
      summarized as follows: (a) detect impaired cardiac performance, (b) grade
      severity of cardiac failure and classify functional capability, and (c) assess
      effects of interventions. Several different methods are available to make these
      assessments, and we have to ask ourselves how well exercise testing achieves
      these objectives. It has to be kept in mind that the power generated by the
      exercising muscles is dependent on the oxygen delivery to the skeletal muscles.
      Oxygen uptake is the result of an integrated performance of the lungs, heart, and
      peripheral circulation. In patients, as well as in normal subjects, oxygen uptake
      is related to hemodynamic indices such as cardiac output, stroke volume, or
      exercise duration when a stepwise regulated maximal exercise protocol is used.
      However, there are major differences in the concept of a true maximum in normal
      subjects versus heart failure patients. Fit-normal subjects will achieve a real
      maximal oxygen uptake, whereas patients may stop testing before a maximum is
      reached because of symptoms such as dyspnea or leg fatigue. Therefore, it is
      better if the actual oxygen uptake can be measured. "Peak" rather than true
      maximal oxygen uptake has been suggested for the classification of the severity
      of heart failure. Peripheral factors modify the cardiac output through such
      factors as vascular resistance, organ function, and hormonal release. Maximal
      exercise will stress the cardiovascular system to a point where the weakest chain
      will impose a limiting effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514234
TI  - Contribution of bradykinin to the cardiovascular effects of ramipril.
AB  - From pharmacologic investigations and clinical studies it is known that
      angiotensin-converting enzyme (ACE) inhibitors exhibit additional local actions,
      which are not related to hemodynamic changes and which cannot be explained simply
      by interference with the renin-angiotensin system with subsequent inhibition of
      angiotensin II formation. Because ACE is identical to kininase II, which
      inactivates the nonapeptide bradykinin (BK), potentiation of BK might be
      responsible for these additional effects of ACE inhibitors. To prove the
      specificity of BK-mediated effects by ACE inhibition, we used the specific B2
      kinin receptor antagonist HOE 140 in different models: endothelial cell cultures;
      atherosclerosis in high-cholesterol-fed rabbits; neointima formation with smooth
      cell proliferation and migration after endothelial denudation in rats; myocardial
      ischemia in rats, rabbits, and dogs; and left ventricular hypertrophy in rats.
      The beneficial effects of ramipril or BK given in non-blood pressure-lowering
      doses in these models were abolished by HOE 140 (icatibant). Ramipril exerts
      cardioprotective effects in different experimental models. The formation of the
      endothelial autacoids nitric oxide and prostacyclin, enhanced when BK degradation
      is inhibited by ACE inhibition, may contribute to the observed beneficial
      effects.

PMID- 7514237
TI  - Validation of primary and secondary outcomes and classification of mode of death
      among patients with clinical evidence of heart failure after a myocardial
      infarction: a report from the Acute Infarction Ramipril Efficacy (AIRE) Study
      Investigators.
AB  - The AIRE study--a trial involving over 2,000 patients with clinical heart failure
      after myocardial infarction--assessed different outcomes. The primary outcome was
      total mortality. The secondary outcome was time to death, or progression to
      severe/resistant heart failure, reinfarction or stroke. Tertiary analyses
      included hospitalization and mode of death. To obtain maximum quality in the
      validation of outcomes and to optimize the quality of the data in the study, an
      end-points committee reviewed all data following preset definitions prior to code
      break. All definitions used are reported here. Experience of the validation
      process demonstrated that there are wide variations in clinical practice and
      terminology not only among countries but also among individual investigators.
      Variation in the clinical handling and treatment of patients makes it imperative
      to validate outcomes centrally on the basis of available facts.

PMID- 7514236
TI  - Early or late ACE inhibition after myocardial infarction.
AB  - There is justifiable enthusiasm for the use of angiotensin-converting enzyme
      (ACE) inhibitors in patients with heart failure. However, early after an acute
      myocardial infarction, the benefits (or harm) from use of these agents in
      individual patients may depend on the critical balance between the ischemic
      problem (the extent of coronary artery narrowing and risk of vessel occlusion)
      against the need to preserve remaining ventricular function. Patients who are
      hemodynamically stable without ongoing chest pain but with significantly impaired
      ventricular function seem likely to gain most from treatment with ACE inhibitors.
      Extrapolation to the acute infarct situation from the recently published trials
      in chronic stable heart failure may mislead, and the findings of a number of
      large ongoing mortality trials in patients with recent myocardial infarction are
      awaited.

PMID- 7514238
TI  - Effect of angiotensin-converting enzyme inhibitors in left ventricular
      dysfunction: results of the studies of left ventricular dysfunction in the
      context of other similar trials.
AB  - Over 13,000 patients have been randomized in 35 long-term trials of the use of
      angiotensin-converting enzyme (ACE) inhibitors in patients with heart failure or
      left ventricular dysfunction. Overall, there is a clear reduction in mortality
      and hospitalizations for heart failure and myocardial infarction with a trend
      toward fewer sudden deaths. Furthermore, there is a significant reduction in
      myocardial infarction in three of the larger trials. These benefits have been
      demonstrated with several different agents and are consistently seen in various
      subgroups of patients defined by symptomatic status, etiology of left ventricular
      dysfunction, age, and gender. However, benefits were greatest among patients with
      the lowest ejection fraction. In conclusion, ACE inhibitors are of established
      value in patients with heart failure and/or left ventricular dysfunction.

PMID- 7514239
TI  - Multiple-dose pharmacokinetics of ramipril in patients with chronic congestive
      heart failure.
AB  - Thirteen patients with chronic congestive heart failure of NYHA class II-III
      received multiple doses (14 days) of ramipril (5 mg once daily); the
      concentrations of ramipril and ramiprilat in plasma, as well as ramipril,
      ramiprilat, glucuronides, diketopiperazine, and diketopiperazine acid in urine
      were measured at various times for 14 days. One patient dropped out after the
      first day due to hypotension and another who accidentally received another ACE
      inhibitor additionally was excluded, so that 11 patients completed the study.
      Ramipril and ramiprilat in plasma were determined by radioimmunoassay, and
      ramipril and its metabolites in urine were measured by gas chromatography in the
      laboratories of Hoechst AG. Peak concentrations of the active substance
      ramiprilat were reached after about 4 h and amounted to 22.3 +/- 11.1 ng/ml after
      the first dose, and a peak concentration of 26.6 +/- 10.0 ng/ml was observed 2.5
      +/- 1.4 h on average after administration on day 14. Practically no accumulation
      was observed for ramiprilat; the AUD (0-24 h) values increased from 191.3 +/-
      83.1 ng.h/ml for the first study day to 238.3 +/- 98.0 ng.h/ml for day 14. As
      expected, only very small fractions of the dose were excreted with urine as
      unchanged ramipril and ramipril glucuronide. Ramiprilat is excreted with urine to
      a larger extent than is rampiril--on average 6.6 +/- 3.0% on the first day and
      12.2 +/- 3.8% on day 14. The total amount excreted increased by 34% on average,
      and was mainly due to an increased ramiprilat excretion.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7514240
TI  - The effects of ACE inhibition on progression of atherosclerosis.
AB  - Angiotensin-converting enzyme inhibitors have been extensively studied and
      established in the treatment of hypertension, heart failure, and ventricular
      dysfunction. They have various cardiac and vascular protective effects, but the
      relevant mechanisms of action in these areas remain to be fully understood.
      Possible effects of converting-enzyme inhibition related to maintenance of normal
      endothelial function and inhibition of atherosclerosis should be distinguished
      from effects on myointimal proliferation related to vascular injury and
      regression of vascular hypertrophy from blood pressure reduction. Experimental
      animal studies have showed benefit from converting-enzyme inhibition in
      preventing myointimal proliferation after vascular injury in some species, but no
      such effect has been shown in clinical studies of restenosis following coronary
      angioplasty. Laboratory studies have demonstrated a protective effect of
      converting-enzyme inhibition on endothelial vasomotor function. Further studies
      have demonstrated prevention of atherosclerosis in hyperlipidemic rabbits and
      cholesterol-fed cynomolgus monkeys. Possible mechanisms of action apart from
      blood pressure lowering include inhibition of angiotensin II and other tissue
      growth factors and accumulation of kinins. These data, among others, provide
      sufficient rationale for clinical studies to determine whether converting-enzyme
      inhibitors can reduce atherosclerotic disease and thus widen their application as
      cardiac and vascular protective agents.

PMID- 7514241
TI  - AML-1 gene rearrangement and AML-1-ETO gene expression as molecular markers of
      acute myeloblastic leukemia with t(8;21).
AB  - Rearrangements of the AML-1 gene on chromosome 21 as well as transcriptional
      expression of AML-1-ETO fusion gene were studied in 35 leukemic patients with
      t(8;21)(q22;q22). A panel of probes generated from the AML-1 gene regions
      flanking the breakpoint on chromosome 21 allowed us to detect the rearrangement
      in 24 out of 29 patients. A specific nested reverse transcriptase/polymerase
      chain reaction (RT/PCR) was developed to detect the t(8;21), either at diagnosis
      or as minimal residual disease. PCR amplification products were obtained in ten
      out of 11 patients investigated, and the sensitivity of the reaction was
      estimated to be between 1 x 10(4) and 1 x 10(-5) cell. An AML-1 rearrangement was
      also detected in one patient with 8q- and only one chromosome 21, but without
      21q+. This indicated that the molecular rearrangement of the der(8) chromosome is
      more important than the reciprocal one in the malignant process.

PMID- 7514242
TI  - AML1/ETO fusion mRNA can be detected in remission blood samples of all patients
      with t(8;21) acute myeloid leukemia after chemotherapy or autologous bone marrow
      transplantation.
AB  - The chromosomal translocation t(8;21)(q22;q22) in acute myeloid leukemia (AML)
      can be detected by a reverse transcription-polymerase chain reaction (RT-PCR) for
      the chimeric AML1/ETO transcript. We have evaluated the clinical relevance of
      this method for monitoring and detection of minimal residual disease (MRD) in
      seven patients who reached a complete hematological remission (CHR) after
      chemotherapy or autologous bone marrow transplantation (ABMT). Peripheral blood
      (PB) samples of five patients in first continuous complete remission (CCR) were
      still PCR-positive at a frequency of 1 in 10(5) cells after 7, 8, 8, 10 or 66
      months. Chemotherapy led to a reduction from first- to second-step PCR-positivity
      in three serially monitored patients. AML1/ETO mRNA was also detected in the PB
      of two patients in CCR, 10 or 12 months after ABMT. PB and bone marrow (BM)
      showed identical results in all samples tested simultaneously. AML1/ETO fusion
      transcripts were neither found in the PB and BM of a healthy individual, nor in
      the PB of a patient after allogeneic BMT for cytogenetically proven t(8;21)
      leukemia. Our results indicate the presence of cells carrying the AML1/ETO
      rearrangement in the PB and BM of all patients in CHR after chemotherapy or ABMT
      for t(8;21)-positive AML. While this finding raises interesting questions about
      the biology of acute leukemia, it limits the value of the AML/ETO RT-PCR for the
      prediction of impending relapse.

PMID- 7514243
TI  - Signal transduction of steel factor and granulocyte-macrophage colony-stimulating
      factor: differential regulation of transcription factor and G1 cyclin gene
      expression, and of proliferation in the human factor-dependent cell line MO7.
AB  - Steel factor (SF) synergizes with a variety of hemopoietins to support the growth
      and differentiation of human progenitor cells. The human factor-dependent cell
      line MO7 has been used as a model to study the interaction of SF with other
      growth factors such as GM-CSF, because both factors support the proliferation of
      this cell line and are synergistic in combination. Previous studies have shown
      that this effect is not readily explained by the synergistic activation of early,
      cytosolic signal transduction intermediates such as tyrosine kinases, Raf-1, MAP2
      kinase, or phospholipase C gamma. In an attempt to further explore the biological
      and biochemical mechanisms of the synergy between SF and GM-CSF, we examined the
      effects of these growth factors on the regulation of nuclear proto-oncogenes,
      cell cycle control genes, and G1-->S transition of MO7 cells. Individually, GM
      CSF was a much more potent growth factor for MO7 cells than SF, particularly
      under serum-free conditions. Only GM-CSF, but not SF, was able to stimulate G1-
      >S transition of MO7 cells after factor deprivation for 24 h. Northern blot
      analyses showed also differential effects of GM-CSF and SF on the expression of
      some nuclear proto-oncogenes and G1 cyclins. GM-CSF (10 ng/ml), but not SF (20
      ng/ml) increased the expression of c-myc and cyclin D2 mRNA, whereas both factors
      caused transient increases of c-fos and cyclin D3 mRNAs. When added
      simultaneously, GM-CSF and SF induced an at least additive increase of c-fos mRNA
      expression; this effect required the presence of fetal calf serum. No additive
      effects of GM-CSF and SF on c-myc, cyclin D2 or D3 mRNA expression were observed.
      C-jun and c-myb mRNAs were constitutively expressed in the MO7 cell line, but not
      further increased after stimulation with GM-CSF or SF for 15 min to 48 h. The
      inability of SF to induce growth promoting genes such as c-myc and cyclin D2 may
      explain why this cytokine does not support sustained proliferation of MO7 cells.
      These observations suggest that SF and GM-CSF exert different effects on the
      expression of genes involved in regulatory pathways of cell proliferation, but
      the molecular mechanism of synergy remains to be elucidated.

PMID- 7514244
TI  - Combination of hematopoietic growth factors containing IL-3 induce acute myeloid
      leukemia cell sensitization to cycle specific and cycle non-specific drugs.
AB  - Laboratory studies have suggested that hematopoietic growth factors (GF),
      combined with cytosine-arabinoside (Ara-C) can enhance cytotoxic effects of this
      agent against acute myeloid leukemia (AML) cells. While clinical trials based on
      this growth factor/chemotherapy combination (GF/CT) are progressing with
      discordant results, further information regarding the underlying mechanisms have
      been reported supporting this rationale and requiring additional investigation.
      To assess the role of cytokinetic changes in the GF/CT strategy and to evaluate
      if chemotherapeutic agents regimens other than Ara-C, when combined with GF, can
      enhance their cytotoxic effects, we have primed AML blasts with two cytokine
      combinations and then exposed these cells to the S-phase specific agent Ara-C as
      well as to the phase non-specific drug daunorubicin (DNR) and to the alkylating
      agent 4-hydroperoxycyclophosphamide (4-HC). The two cytokine combinations used
      for priming AML blasts were: (i) interleukin-3 (IL-3) + granulocyte-macrophage
      colony-stimulating factor (GM-CSF) + granulocyte colony-stimulating factor (G
      CSF); and (ii) GM + G-CSF. Cytokinetic analysis in ten AML samples and clonogenic
      growth of leukemic colonies (CFU-L) in methylcellulose were used to detect
      proliferative and cytotoxic effects on AML samples. We report that in AML
      clonogenic cell growth can be stimulated by cytokines in 50% of the samples
      (4/8), and that Ara-C sensitization clearly occurs in two out of these four
      samples. Among the different cytokine combinations tested, the one containing IL
      3 was the most effective through a cytokinetic mechanism consistent with
      recruitment (averaged G0 decrease p = 0.04; S-phase increase p = 0.005).
      Furthermore we observed increased cytotoxicity also to the phase non-specific
      drugs DNR and 4-HC, which may be mediated by other mechanisms recently described.
      We conclude that GF/CT combinations may also be beneficial in regimens containing
      drugs other than Ara-C, used for AML treatment, including bone marrow
      transplantation conditioning regimens.

PMID- 7514246
TI  - Structural analysis of the deoxycytidine kinase gene in patients with acute
      myeloid leukemia and resistance to cytosine arabinoside.
AB  - Deficiency of deoxycytidine kinase (dCK) activity represents one possible cause
      of resistance to cytosine arabinoside (ara-C). Mutations of the dCK gene have
      recently been shown to be responsible for dCK deficiency and increased resistance
      in vitro. In order to define the relevance of this mechanism in vivo, we analyzed
      the dCK gene in 16 adult patients with relapsed/refractory acute myeloid leukemia
      (AML) and clinical resistance to standard-dose and/or high-dose ara-C. Southern
      blot analysis using genomic DNA from peripheral blood or bone marrow samples
      containing > or = 70% leukemic blasts and agarose gel electrophoresis of cDNA
      obtained by RT-PCR did not reveal gross rearrangements of the dCK gene.
      Sequencing of the dCK coding region showed point mutations in seven patients.
      Besides two silent mutations (or RFLPs) in codon 42 and 86, base pair mutations
      resulting in amino acid replacements were found in five patients affecting codon
      20, 93, 98, 99, and 154, respectively. dCK cDNA clones from three patients with >
      or = 50% of sequenced clones revealing the specific base pair alteration were
      bacterially expressed in E. coli and analyzed for dCK activity. Normal enzyme
      activity was found in two patients (codon 20 and 98), and a complete loss of
      activity in one patient (codon 99). We conclude that structural alteration of the
      coding region of the dCK gene represents one possible mechanism for ara-C
      resistance in vivo, but, considering the frequency of this event, other
      mechanisms may play a more important role for clinical resistance to ara-C in
      patients with AML.

PMID- 7514245
TI  - Bcr-abl-positive and -negative clonogenic cells in CML patients undergoing long
      term interferon treatment.
AB  - Bone marrow (BM) and peripheral blood cell (PBC) samples of 11 Philadelphia (Ph)
      chromosome-positive chronic myelogenous leukemia (CML) patients in long-lasting
      hematologic remission induced by interferon (IFN) treatment were examined for the
      presence of leukemic hematopoietic precursor cells. Southern blot analysis
      revealed residual leukemic cells in BM samples of four patients, whereas seven
      patients showed no aberrant bands. Reverse transcription polymerase chain
      reaction (RT-PCR), however, amplified bcr-abl-specific cDNA in unfractionated BM
      or PBC samples in all 11 patients. The patients demonstrating bcr rearrangements
      in Southern blots had either a mosaic pattern (three patients) of bcr-abl
      negative and positive colony-forming precursors (CFU-GEMM, BFU-E, CFU-GM, CFU
      Mega), or all colonies were derived from leukemic precursors (one patient).
      However, in soft agar cultures of four patients without aberrant bands in
      Southern blots, only colonies without amplifiable bcr-abl transcripts were
      detectable. In another patient, few bcr-abl-positive colonies were found after 44
      months of treatment, but not after 53 and 56 months of therapy. In these
      patients, therefore, residual disease detectable by PCR analysis of
      unfractionated cell samples does not appear to reside in the colony-forming cell
      compartment. The prognostic implications of these observations and the nature of
      the remaining bcr-abl-positive cells within unfractionated cell samples remain to
      be determined.

PMID- 7514247
TI  - Investigation of karyotypic, morphologic and clinical features in patients with
      acute myeloid leukemia blast cells expressing the neural cell adhesion molecule
      (CD56).
AB  - The mechanisms of extramedullary leukemic infiltration are not well
      characterized. The cell-surface glycoprotein CD56, which is identical to the
      neural cell adhesion molecule, may be involved. Using the Leu-19 antibody and
      flow cytometric methods, the leukemic blasts of 22% (70 of 314) of patients were
      CD56 positive. This was most common in acute monocytic leukemia (15 of 18, 83%)
      and in patients with the cytogenetic abnormalities t(8;21) (seven of 13, 54%) and
      trisomy 8 (nine of 22, 41%). CD56 expression was not associated with
      extramedullary leukemic infiltration, but was correlated with positivity for
      CD11b (p < 0.001), CD14 (p < 0.001) and CD19 (p = 0.018). Although associated
      with morphologic and cytogenetic features, CD56 expression alone cannot account
      for most instances of tissue infiltration in acute myeloid leukemia (AML).

PMID- 7514248
TI  - Mast cell growth factor (c-kit ligand) restores growth of multipotent progenitors
      in myelodysplastic syndrome.
AB  - In vitro growth of primitive hematopoietic progenitors is severely impaired in
      the myelodysplastic syndromes (MDS). To determine if the c-kit ligand mast cell
      growth factor (MGF) can improve progenitor growth in MDS, we evaluated in vitro
      responsiveness of bone marrow progenitors from 25 patients to MGF and/or GM-CSF,
      interleukin-3 (IL-3) and PIXY 321, and examined the relationship between
      progenitor response and cellular expression of the c-kit receptor. MGF and
      erythropoietin gave rise to macroscopic colonies and dose-dependently increased
      CFU-GEMM and BFU-E up to 27-fold in 15 (60%) and 20 (80%) patients, respectively.
      Among 17 patients with absent growth in lymphocyte-conditioned media, MGF
      stimulated CFU-GEMM recovery in 59%, compared to 23% with PIXY 321, 12% with IL-3
      and 8% with GM-CSF. Cytokine combinations did not augment recovery of
      erythropoietin-dependent progenitors above that achieved with MGF alone. MGF
      and/or IL-3 were comparatively weak stimulants of CFU-GM formation, whereas GM
      CSF and PIXY in combination with MGF increased colony number 2- to 15-fold in 60
      and 70% of patients, respectively, while preserving maturation competence as
      evidenced by colony composition and increased colony/cluster ratio. The
      stimulatory effects of MGF were observed in all morphologic categories of MDS
      except chronic myelomonocytic leukemia. A mononuclear cell population expressing
      the c-kit receptor was identified by flow cytometry in 57% of cases. Neither SR-1
      reactivity nor cytogenetic pattern predicted progenitor response to MGF. These
      data indicate that MGF improves the colony-forming capacity of hematopoietic
      progenitors in MDS and is a potent co-stimulant of multipotent and committed
      progenitor recovery. The heterogeneity in MGF responsiveness implies an intrinsic
      defect in growth regulation not explained by cellular loss of c-kit display.

PMID- 7514249
TI  - Growth analysis of marrow CD34-positive hematopoietic progenitor cells in
      patients with myelodysplastic syndromes.
AB  - The in vitro colony-forming capacities of marrow CD34-positive (CD34+) cells from
      25 patients with myelodysplastic syndromes (MDS) were studied. In all patients
      this purified cell population showed erythroid (burst-forming unit erythroid; BFU
      E) or non-erythroid colony growth, both of which were more restricted than non
      purified mononuclear cell population under stimulation with erythropoietin (EPO)
      or granulocyte/macrophage colony-stimulating factor (GM-CSF) alone. MDS patients
      examined were put into two groups; refractory anemia (RA) or RA with ringed
      sideroblasts (RA/RARS) and RA with excess of blasts (RAEB) or RAEB in
      transformation (RAEB/RAEB-t). The CD34+ cells of both RA/RARS and RAEB/RAEB-t
      exhibited a similarity to the cells of normal individuals in their responsiveness
      to the addition of interleukin 6 (IL-6), IL-3 or stem cell factor (SCF). SCF
      caused powerful but highly variable responses in both erythroid and nonerythroid
      colony formation as compared with IL-6 or IL-3. We demonstrated that MDS marrow
      hematopoietic progenitor cells reactive to GM-CSF or EPO were additionally
      stimulated with early-acting hematopoietic growth factors including IL-6, IL-3
      and SCF in a fashion similar to those of normal individuals.

PMID- 7514250
TI  - Plastic-adherent cells in human bone marrow generate long-term hematopoiesis in
      vitro.
AB  - This study demonstrates that the human bone marrow mononuclear cell fraction that
      adheres to plastic during a 2-h incubation period includes stromal precursors and
      hematopoietic progenitor cells that can sustain hematopoiesis for at least 5
      weeks in a long-term culture (LTC) system. Delta (delta) assays were performed on
      the 2-h plastic-adherent fraction of mononuclear cells, by assaying the numbers
      of CFU-GM released into the culture supernatant during 1 week of incubation, to
      investigate the properties of the original progenitor cells. The plastic-adherent
      delta (P delta) progenitor cells all express CD34, and a variable proportion
      express Thy-1. The numbers of CFU-GM produced are directly related to the numbers
      of mononuclear cells used to initiate the cultures, and limiting dilution
      experiments indicate a frequency for P delta cells of 2.5-10/10(5) mononuclear
      cells. The numbers of CFU-GM produced by individual P delta cells at limiting
      dilution vary considerably within experiments but the distributions of CFU-GM per
      P delta progenitor show little variation between samples. On average, P delta
      cells generate 6-9 early CFU-GM scored on day 21 of culture; 10-23 CFU-GM scored
      on day 14, and 18-40 mature CFU-GM scored on day 7. These results show that
      plastic-adherent cells in human bone marrow are capable of sustained
      hematopoiesis in vitro and of producing a spectrum of clonogenic progeny. They
      form the basis of an assay for investigating the kinetics of early human
      hematopoietic progenitor cells.

PMID- 7514251
TI  - Heterogeneity among Whipple's-disease-associated bacteria.

PMID- 7514252
TI  - RANTES and chemokines in rheumatoid arthritis.

PMID- 7514253
TI  - Protection of low-density lipoprotein from oxidation by 3,4
      dihydroxyphenylethanol.

PMID- 7514254
TI  - Risperidone for hallucinations in levodopa-treated Parkinson's disease patients.

PMID- 7514255
TI  - Dosimetry studies utilizing the Urolase right angle firing neodymium:YAG laser
      fiber.
AB  - Neodymium:YAG laser application was performed with the Urolase right angle laser
      fiber in a potato model and then in vivo in 29 canine prostates in an attempt to
      define dosimetry and optimal treatment parameters required to maximize tissue
      ablation and treatment efficacy. Depth and volume of prostatic tissue ablation
      for single, continuous laser applications with the Urolase fiber were measured at
      variable power settings from 20 to 60 watts, while holding total energy delivery
      constant. Peak tissue ablation was observed at 40 watts--up to a maximum of 21 mm
      tissue penetration in the canine model with a mode of 15 mm. The mean depth of
      tissue destruction at 40 watts power setting was 15.7 mm, with a mean volume of
      tissue ablation of 5.5 cc. The mean depth of tissue penetration at 40 watts was
      more than 30% greater than that observed at 60 watts, and the mean volume of
      tissue ablation was more than 60% greater than that observed at 60 watts. Holding
      the power setting constant at 40 watts, the extent of tissue ablation was
      measured for variable treatment times from 60 to 120 seconds. As treatment time
      was increased from 60 to 90 seconds, tissue ablation increased significantly.
      However, beyond 90 seconds of continuous laser application at 40 watts, a plateau
      in tissue effects was observed, with no real increase in tissue ablation between
      90 and 120 seconds. Interruption or discontinuous laser application produced
      tissue effects which were significantly less than those observed for a single
      continuous 90 second laser treatment.

PMID- 7514256
TI  - Comparative study of intraarterial and intravenous anticoagulants in
      microvascular anastomoses.
AB  - Using a rat femoral artery crush-avulsion model previously described by the
      authors (Rooks et al.: Microsurgery 14: 130-134, 1993), we analyzed the relative
      efficacy of intraarterially delivered anticoagulants against similar systemically
      administered intravenous anticoagulants with double blinded experimentation. The
      model uses a standardized crush of approximately 0.3 J and a standardized
      avulsion. This is followed by vascular stasis for 90 seconds after vessel repair.
      All rats were limited to 175 to 225 gm in weight to control vessel size.
      Urokinase, heparin sodium, and dextran (40,000 Dalton) were evaluated in this
      study. A statistically significant (p-value = 0.02) increase in urokinase
      efficacy was found with intraarterial delivery. (Patency rate increased from 40%
      to 100%). No advantage to intraarterial delivery was evident with either dextran
      or heparin. There was a dose related improvement in patency with heparin that was
      unaffected by delivery route. (Patency increased from 30% to 80% with a
      statistical p-value of 0.018.)

PMID- 7514257
TI  - Distortion in the parental transmission of HLA-A2 haplotypes (locus A,B).
AB  - The parental transmission of HLA-2 antigen in association with the epitopes BW4
      and BW6 (class I HLA haplotypes locus A,B) was analyzed in sons and daughters
      from 42 families in which one of the parents carried the HLA-A2 antigen. When the
      parental transmission of A2 BW4 and A2 BW6 was compared, it was observed that a
      significantly higher number of siblings inherited the haplotype A2 BW4 from the
      paternal than from the maternal haplotype. Although the number of cases is small,
      the mode of inheritance of haplotype A2 BW6 was completely different. The genetic
      distortion in the transmission of HLA-2 BW4 and HLA-2 BW6 was observed in
      children of both sexes.

PMID- 7514259
TI  - Idiopathic sudden sensorineural hearing loss. University hospital experience.
AB  - Thirty patients with idiopathic sudden sensorineural hearing loss who presented
      to the University Hospital between January 1985 to January 1992 are presented.
      The combined regime of bed rest, intravenous dextran 40, vasodilator and steroid
      therapy produced good improvement in 63.4% of patients. Unfavourable prognostic
      factors were found to be, hearing loss of more than two weeks duration, vertigo
      and bilateral hearing loss.

PMID- 7514258
TI  - Prevalence of hepatitis C virus antibodies in blood donors in Malaysia.
AB  - Hepatitis C virus (HCV) is the chief aetiologic agent for the parenterally
      transmitted Non-A, Non-B (NANB) hepatitis. This preliminary study was done to
      determine the prevalence of anti-HCV in the blood donor population. Blood from
      3,540 donors who donated blood to the Blood Services Centre, Hospital, Kuala
      Lumpur, from 25th August 1991 to 13th January 1992, was tested for anti-HCV using
      both the Ortho and Abbott 2nd Generation ELISA test kits. ELISA positive
      specimens were repeated twice but no confirmatory test was done. There were 53
      out of 3,540 (1.49%) blood donors who were repeatedly reactive to anti-HCV by
      ELISA. We plan to do further tests to confirm the results, using RIBA-2 or Abbott
      Neutralising test. Twenty eight out of 1,713 (1.63%) Malays, 22 out of 1,373
      (1.60%) Chinese and 2 out of 393 (0.50%) Indians had antibodies to HCV. There was
      no significant difference in prevalence in the different age groups. The majority
      of donors tested were males (3,511 out of 3,540) of which 53 (1.50%) were anti
      HCV positive. Only 29 females were tested and all were negative. To determine
      infectivity of the anti-HCV positive cases we would like to introduce testing for
      RNA by polymerate chain reaction (PCR). Screening all donated blood for anti-HCV
      will decrease, but not totally eliminate, post-transfusion hepatitis.

PMID- 7514260
TI  - Thermoregulatory effects of chlorpyrifos in the rat: long-term changes in
      cholinergic and noradrenergic sensitivity.
AB  - Subcutaneous injection of a sublethal dose of chlorpyrifos (CHLP), an
      organophosphate (OP) pesticide, causes long-term inhibition in cholinesterase
      activity (ChE) of brain, blood, and other tissues. Such prolonged inhibition in
      ChE should lead to marked behavioral and autonomic thermoregulatory patterns,
      especially in terms of altered noradrenergic and cholinergic sensitivity. To
      evaluate the behavioral and autonomic effects of long-term ChE inhibition, Long
      Evans rats were implanted with radiotelemetry transmitters that continuously
      monitored core temperature (Tc), heart rate (HR), and motor activity (MA). These
      parameters were monitored for 7 days following a single injection of peanut oil
      (vehicle control) or 280 mg/kg CHLP. CHLP led to a significant reduction in Tc
      during the first night after treatment but had no other effects on Tc. CHLP also
      resulted in a significant elevation in HR which lasted for approximately 72 h.
      Motor activity was unaffected by CHLP. Cholinergic and noradrenergic drug
      sensitivity was assessed between 7 and 25 days after CHLP. CHLP-treated rats were
      more sensitive to norepinephrine as based on a greater hyperthermic response. MA
      of CHLP-treated rats was more sensitive to scopolamine. On the other hand, the
      hypothermic effects of oxotremorine (0.4 mg/kg) were nearly abolished by CHLP
      treatment, indicating tolerance to cholinergic stimulation. The tachycardic
      effects of methyscopolamine were also greater in the CHLP group. Overall, the
      acute effects of CHLP are unusual compared to other OP's in that there is no
      hypothermic response, an attenuated nocturnal elevation in Tc and a prolonged
      elevation in HR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514261
TI  - The H1 receptor agonist 2-(3-chlorophenyl)histamine activates Gi proteins in HL
      60 cells through a mechanism that is independent of known histamine receptor
      subtypes.
AB  - In dibutyryl-cAMP-differentiated HL-60 cells, histamine H1 and formyl peptide
      receptors mediate increases in the cytosolic Ca2+ concentration ([Ca2+]i) via
      pertussis toxin-sensitive G proteins of the Gi family. We compared the effects of
      2-(3-chlorophenyl)-histamine (CPH) [2-[2-(3-chlorophenyl)-1H-imidazol-4-yl]
      ethanamine], one of the most potent and selective H1 receptor agonists presently
      available, with those of histamine and N-formyl-L-methionyl-L-leucyl-L
      phenylalanine (fMLP) in these cells. CPH increased [Ca2+]i through Ca2+
      mobilization and Ca2+ influx. Unlike histamine-induced rises in [Ca2+]i, those
      induced by CPH were not desensitized in a homologous manner, and there was no
      cross-desensitization between CPH and histamine. Like fMLP, CPH activated
      phospholipases C and D, tyrosine phosphorylation, superoxide anion formation, and
      azurophilic granule release. The effects of CPH on [Ca2+]i, phospholipase D, and
      superoxide anion formation were inhibited by pertussis toxin. CPH and fMLP
      stimulated high affinity GTP hydrolysis by Gi proteins in HL-60 membranes. They
      also enhanced binding of guanosine-5'-O-(3-thio)triphosphate and GTP azidoanilide
      to, and cholera toxin-catalyzed ADP-ribosylation of, Gi protein alpha subunits.
      Histamine receptor antagonists did not inhibit the stimulatory effects of CPH,
      and CPH did not reduce fMLP binding in HL-60 membranes. Our data suggest that CPH
      activates Gi proteins in HL-60 cells through a receptor agonist-like mechanism
      that is, however, independent of known histamine receptor subtypes and formyl
      peptide receptors. CPH may be an agonist at an as yet unknown histamine receptor
      subtype or, by analogy with other cationic-amphiphilic substances, may activate G
      proteins directly. Future studies will have to take into consideration the fact
      that CPH, in addition to activating H1 receptors, may show other, most
      unexpected, stimulatory effects on G protein-mediated signal transduction
      processes.

PMID- 7514262
TI  - The beta subunit of neuronal nicotinic acetylcholine receptors is a determinant
      of the affinity for substance P inhibition.
AB  - Substance P is known to inhibit nicotinic acetylcholine receptors from neuronal
      tissue, skeletal muscle, and electroplaque. The interaction of substance P with
      specific combinations of neuronal nicotinic acetylcholine receptor subunits was
      studied by expressing various combinations of subunits in Xenopus oocytes. The
      response to acetylcholine was inhibited by substance P with all subunit
      combinations tested; however, the apparent affinity for substance P varied by 20
      30-fold. The affinity seemed to be dependent on the beta subtype expressed (beta
      4 or beta 2). This suggests that the beta subunit may contribute, at least
      partially, to the substance P binding site. In the case of the alpha 7 subtype,
      which forms a homooligomeric receptor, the apparent affinity for substance P was
      intermediate between those of the two beta subtypes coexpressed with either alpha
      3 or alpha 4. As previously found, the inhibition was noncompetitive.
      Furthermore, the inhibition was not voltage dependent and, therefore, is unlikely
      to be due to substance P blocking the channel within the transmembrane portion of
      the pore.

PMID- 7514263
TI  - Direct demonstration of high affinity interactions of immunosuppressant drugs
      with the drug binding site of the human P-glycoprotein.
AB  - The interactions between the human P-glycoprotein (Pgp) and two different types
      of immunosuppressant drugs known to modulate multidrug resistance in tumor cells
      have been directly investigated using our newly developed drug-stimulated ATPase
      assay for Pgp function. The macrolides FK506 and FK520 stimulate the Pgp-ATPase
      activity with affinities in the 100 nM range, nearly 10 times higher than that of
      verapamil, a well known Pgp substrate. On the other hand, the cyclic peptides
      cyclosporin A and dihydrocyclosporin C do not stimulate the Pgp-ATPase activity
      at all. They do, however, act as potent competitive inhibitors of verapamil
      stimulated Pgp-ATPase activity, with affinity constants in the 20-25 nM range.
      Thus, although these two classes of immunosuppressant drugs affect the Pgp in
      different ways, they both probably interact with high affinity at the transported
      drug binding site(s) of the Pgp, which would explain their ability to resensitize
      multidrug-resistant cells to the killing action of certain antitumor drugs.
      Possible implications of these findings for Pgp function, cancer chemotherapy,
      and immunosuppression are discussed.

PMID- 7514264
TI  - Biochemical studies on PT523, a potent nonpolyglutamatable antifolate, in
      cultured cells.
AB  - Studies on the mode of action of PT523 [N alpha-(4-amino-4-deoxypteroyl)-N delta
      hemiphthaloyl-L-ornithine], a potent nonpolyglutamatable antifolate, were carried
      out in sensitive and resistant H35 rat hepatoma cell lines in culture, to compare
      it with other antifolates, including three dihydrofolate reductase (DHFR)
      inhibitors, i.e., methotrexate (MTX), gamma-fluoro-MTX, and trimetrexate (TMQ),
      two thymidylate synthase inhibitors, i.e., N10-propargyl-5,8- dideazafolate
      (PDDF) and 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolate (dmPDDF), and the
      glycinamide ribonucleotide formyltransferase inhibitor 5,10-dideaza-5,6,7,8
      tetrahydrofolate. PT523 was the most active compound in this group against the
      parental H35 cells, with an IC50 ranging from 2.5 nM for 72 hr of treatment to
      0.21 microM for 2 hr of treatment. Sublines resistant to MTX by virtue of a
      transport defect or a combination of defective transport and increased DHFR
      activity were resistant to PT523 and MTX but not to PDDF, whereas sublines
      resistant to fluoropyrimidines by virtue of increased thymidylate synthase
      activity were resistant to PDDF but not to PT523, TMQ, or MTX. Inhibition of H35
      cell growth by PT523 was associated with a concentration- and time-related
      decrease in de novo dTMP and purine biosynthesis. Growth inhibition by PT523,
      MTX, and TMQ was prevented by leucovorin or a combination of thymidine (dThd) and
      hypoxanthine but not by dThd or hypoxanthine alone; in contrast, growth
      inhibition by dmPDDF was prevented by dThd alone. Intracellular reduced folate
      polyglutamate pools were markedly altered by PT523 treatment, with the most
      pronounced effect being an increase in 7,8-dihydrofolate mono- and polyglutamates
      and a decrease in 5,10-methylene-5,6,7,8-tetrahydrofolate mono- and
      polyglutamates, 5,6,7,8-tetrahydrofolate mono- and polyglutamates, and 10-formyl
      5,6,7,8-tetrahydrofolate mono- and polyglutamates. This pattern was qualitatively
      similar to that observed with MTX and TMQ but different from that observed with
      dmPDDF or 5,10-dideaza-5,6,7,8-tetrahydrofolate, which resulted in little or no
      change in the folate species. Uptake of [3H]MTX and [3H]folinic acid, but not
      [3H]folic acid, by H35 cells was inhibited in a dose-related manner by PT523,
      suggesting that penetration of the cell probably involves, at least in part,
      active transport by the MTX/reduced folate carrier. To determine whether the
      potent cellular effects of PT523 might be due to chemical or enzymic clevage to
      N'-(4-amino-4-deoxypteroyl)-L-ornithine, a potent inhibitor of folylpolyglutamate
      synthetase, the formation of [3H]MTX polyglutamates in CCRF-CEM lymphoblasts
      pulsed with [3H]MTX after preincubation with PT523 was examined.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7514265
TI  - [Biogenesis and secretion of alkaline phosphatase and its mutants in Escherichia
      coli. III. Substitution of N-terminal amino acids of alkaline phosphatase affect
      its biogenesis].
AB  - The effect of the N-terminal amino acid substitution on E. coli alkaline
      phosphatase biogenesis has been studied. The substitutions of Ser, Gln, Tyr, Leu,
      Gly, Ala, Glu, Phe, His, Cys, Lys and Pro for Arg(+1) were obtained by creating
      amber mutation at the corresponding position within phoA gene and expressing this
      mutated gene in E. coli strains that produce the amber-suppressor tRNAs. All
      mutant proteins were shown to translocate across the cytoplasmic membrane and
      possess enzyme activity. The introduction of Pro in +1 position disturbs the
      cleavage of signal peptide whereas the insertion of the other amino acids does
      not change the rates of processing in comparison with wild-type protein. All
      amino acid substitutions affect alkaline phosphatase isoenzyme composition. Some
      experimental evidence were also obtained on the specificity of protease, which
      split off N-terminal Arg during alkaline phosphatase maturation.

PMID- 7514266
TI  - [Cloning, determination of primary structure, and expression of the C-terminal
      segment of human cholesterol-esterase/lipase, containing the antigenic
      determinant of the protein, in Escherichia coli].
AB  - Clone pHICE0.9 was selected from human insulinoma cDNA library by immunoscreening
      with antibodies against total human insulinoma proteins. This clone contains a
      0.9 kb cDNA insert and expresses a fusion protein with beta-galactosidase.
      Nucleotide sequences of 5'- and 3'-terminal regions of this cDNA insert show that
      clone pHICE0.9 expresses a protein which is identical to the C-terminal fragment
      (amino acids 483 to 745) of human pancreatic cholesterol esterase and Homo
      sapiens bile-acid-salt-stimulated lipase from milk. It is concluded that the
      protein fragment contains the antigenic determinant of human cholesterol
      esterase/lipase, and can be used for lipase determination in blood.

PMID- 7514267
TI  - Isolation and chemical characterization of the human B29 and mb-1 proteins of the
      B cell antigen receptor complex.
AB  - A disulfide-linked heterodimeric antigen from human B leukemia cells was detected
      by radioimmunoprecipitation and Western blot analysis using a monoclonal antibody
      (mAb). The mAb was generated against a cell membrane antigen preparation from
      human B prolymphocytic leukemia cells and found to define an extracellular
      epitope of the smaller component (beta chain) of a heterodimeric antigen on human
      B leukemia cells. The antigen from BALL-1, a human B leukemia cell line, and
      fresh (uncultured) B prolymphocytic leukemia cells was found to consist of a 44
      49 kDa (alpha chain) and a 36-40 kDa (beta chain) component. An additional minor
      component of 34 kDa was detected in the reduced antigen from BALL-1. For chemical
      identification of the antigen, we isolated the antigen from a Triton X-100 lysate
      of BALL-1 by immunoaffinity chromatography using the mAb. Determination of the
      amino-terminal amino acid sequences of the alpha and beta chains unequivocally
      identified them as the human mb-1 and B29 proteins, respectively. The sequence
      analyses indicate the molecular heterogeneity of the mb-1 protein and also
      perhaps the heterogeneity of the B29 protein. We detected three forms of the mb-1
      protein which share an identical amino-terminal amino acid sequence and probably
      two forms of the B29 protein which share an identical amino-terminal sequence.
      Our sequence data allowed us to establish the authentic amino-terminal amino acid
      sequence of the human B29 protein which is different from those proposed by
      others based on cDNA sequence analyses. Comparison of the amino-terminal
      sequences of the human mb-1 and B29 proteins with those of the mouse mb-1 and B29
      proteins showed that the majority of the conserved amino acids in the mb-1
      proteins are hydrophobic amino acids. Such conservation of hydrophobic amino
      acids is not observed in the amino termini of the human and mouse B29 proteins. A
      beta-tubulin-like protein was found to be co-purified with the mb-1-B29 antigen
      in the present study. In addition, we found that there is a strong amino acid
      sequence homology between the microtubule-binding domains of certain human
      microtubule-associated proteins and an intracellular segment of the human mb-1
      protein.

PMID- 7514268
TI  - Effect of HIV-1 peptide presentation on the affinity constants of two monoclonal
      antibodies determined by BIAcore technology.
AB  - We studied two monoclonal antibodies (MAbs 9-11 and 41-1) which are specific for
      dominant and conserved epitopes located on HIV-1 transmembrane Gp41. These MAbs
      recognize both Gp41 and a synthetic HIV-1 envelope peptide (39GC) which is a
      fragment of Gp41. The interactions between MAbs 9-11 and 41-1 and 39GC either
      coupled to a sensor chip or to alkaline phosphatase were investigated using
      BIAcore technology. The association and dissociation rate constants as well as
      the affinity constants were determined. BIAcore technology allows real-time
      determination of the interaction between two molecules without the need for any
      labeling, neither isotopic nor enzymatic. The peptide 39GC was immobilized by
      coupling to dextran on the BIAcore biosensor through a disulfide bond with a
      cysteine residue added to the N-terminus of the synthetic peptide. The two native
      cysteine residues located in the loop of Gp41 were protected by ethylcarbamoyl
      residues (CONHC2H5); this chemical modification prevented the formation of the S
      S bridge and in particular the internal loop. We specifically studied the
      interaction between the MAbs and either the protected peptide or the peptide
      whose cysteine residues had been deprotected in situ by alkaline treatment. The
      results showed that MAb 41-1 recognized 39GC either protected (Ka = 7.6 x 10(6) M
      1) or unprotected (Ka = 1.48 x 10(8) M-1), whereas MAb 9-11 recognized only the
      unprotected form (Ka = 2.18 x 10(8) M-1). Our results suggest that the epitope
      MAb 9-11 is directed against a part of the peptide sequence which includes the
      two native cysteines. The difference in affinity observed for MAb 41-1 between
      the protected and the unprotected forms of 39GC was found to be due to a lower
      rate of dissociation for unprotected 39GC; these results illustrate the
      importance of peptide conformation on antibody recognition and might be explained
      by a conformational change due to reconstitution of the internal loop following
      deprotection of the thiol groups. MAbs 9-11 and 41-1 also recognized 39GC
      conjugated to alkaline phosphatase and deprotected. We observed a difference
      between the rate constants for MAb 41-1 binding to free peptide and its binding
      to the peptide-enzyme conjugate which might be due to changes in peptide
      flexibility. In contrast, the rate constants of MAb 9-11 were the same in both
      experiments, suggesting that the rigidity of the internal loop prevents changes
      in 9-11 epitope conformation.

PMID- 7514270
TI  - Immunological relationships among group I and group V allergens from grass
      pollen.
AB  - Specific IgE antibodies have been affinity-purified from recombinant grass pollen
      allergens, and used to identify isoforms of the two major allergens of rye-grass
      pollen, Lol p I and Lol p V and cross-reactive allergens in other grasses. Lol p
      I-specific IgE (affinity-purified from the recombinant protein expressed by clone
      13R which encodes amino acids 96-240 of Lol p I) identified four isoforms of the
      allergen. The same probe recognized cross-reactive epitopes in pollen proteins
      from 14 out of 16 grasses. The allergens identified by Lol p V-specific IgE
      (affinity-purified from the recombinant protein expressed by clones 12R or 19R
      which encode the full Lol p V protein) varied more in their physicochemical
      characteristics than the Group I isoforms. At least eight isoforms of Lol p V
      were identified by the Lol p V-specific IgE. The same probe recognized cross
      reactive epitopes in pollen protein from 13 out of 16 grasses. Group I proteins
      were identified in grasses from two sub-families of the Poaceae, while the Group
      V allergens were only identified in pollen of grasses from one sub-family, the
      Pooideae.

PMID- 7514269
TI  - Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells
      mediating contact-dependent helper function for B cells: identity with the CD40
      ligand.
AB  - "T-cell B-cell Activating Molecule" (T-BAM) is an activation-induced surface
      protein on CD4+ T cells that mediates a contact-dependent signal for B cell
      differentiation and immunoglobulin (Ig) secretion. The T-BAM protein on a helper
      clone of Jurkat (D1.1) was affinity purified using the anti-T-BAM mAb, 5c8. The
      NH2-terminal amino acid sequence of purified T-BAM was determined and found to be
      highly homologous to the predicted NH2-terminal sequence of a T cell ligand to
      the B cell CD40 molecule (CD40-L). From a D1.1 cDNA library, a clone was isolated
      that encodes CD40-L by sequence and drives expression of T-BAM protein on
      transfected cells, demonstrating that the T-BAM and CD40-L genes and proteins are
      identical. Moreover, transfection of T-BAM was shown to confer to non-lymphoid
      cells, the ability to induce B cells to upregulate the expression of surface CD23
      molecules. In previous studies we showed that T-BAM was expressed predominantly
      on activated CD4+ and on few if any CD8+ cells. Although the current work
      confirms that T-BAM is largely restricted to activated CD4+ T cells, we now
      provide definitive evidence that T-BAM can be expressed by a small population of
      CD8+ T cells after activation. Importantly, a subset of CD8+ T cells do not
      express T-BAM after activation and this T-BAM- phenotype is maintained on certain
      CD8+ T cell clones. Taken together, these data unify the biology and structure of
      T-BAM and CD40-L and this synthesis has implications for understanding the T cell
      regulation of the humoral immune response.

PMID- 7514271
TI  - Origins of life. Chemical replication.

PMID- 7514272
TI  - Regulation of NMDA receptors by tyrosine kinases and phosphatases.
AB  - Protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) are key
      enzymes in signal-transduction pathways for a wide range of cellular processes.
      PTKs and PTPs are highly expressed in the central nervous system, which is
      consistent with the importance of tyrosine phosphorylation in neuronal function.
      Protein phosphorylation is known to be involved in the regulation of
      neurotransmitter receptors, but the effects of tyrosine phosphorylation on
      neurotransmitter receptor function in the central nervous system are unknown.
      Here we present evidence that in mammalian central neurons tyrosine
      phosphorylation regulates the function of the NMDA (N-methyl-D-aspartate)
      receptor, a subtype of excitatory amino-acid receptor. NMDA-receptor-mediated
      whole-cell currents and intracellular Ca2+ responses are depressed by inhibition
      of PTKs. Conversely, NMDA currents are potentiated by intracellular application
      of the well characterized PTK pp60c-src. NMDA currents are also potentiated by
      intracellular administration of an inhibitor of PTPs. Protein-tyrosine
      phosphorylation is a new mechanism for regulating NMDA receptors and may be
      important in neuronal development, plasticity and toxicity.

PMID- 7514273
TI  - Regulation of NMDA channel function by endogenous Ca(2+)-dependent phosphatase.
AB  - Protein kinases modulate the activity of several ligand-gated ion channels,
      including the NMDA (N-methyl-D-aspartate) subtype of glutamate receptor. Although
      phosphorylation and dephosphorylation of glutamate receptors may participate in
      several lasting physiological and pathological alterations of neuronal
      excitability, the physiological control of this cycle for NMDA channels has not
      yet been established. Using cell-attached recordings in acutely dissociated adult
      rat dentate gyrus granule cells, we now demonstrate that inhibitors of an
      endogenous serine/threonine phosphatase prolong the duration of single NMDA
      channel openings, bursts, clusters and superclusters. Okadaic acid, a non
      selective phosphatase inhibitor, prolongs channel openings only at a
      concentration that inhibits the Ca2+/calmodulin-dependent phosphatase 2B
      (calcineurin), and is ineffective when Ca2+ entry through NMDA channels is
      prevented. Furthermore, FK506, an inhibitor of calcineurin, mimics the effects of
      okadaic acid. Thus in adult neurons, calcineurin, activated by calcium entry
      through native NMDA channels, shortens the duration of channel openings.
      Simulated synaptic currents were enhanced after phosphatase inhibition, which is
      consistent with the importance of phosphorylation of the NMDA-receptor complex in
      the short- and long-term control of neuronal excitability.

PMID- 7514274
TI  - Synthetic chemistry. Not through the usual channels.

PMID- 7514275
TI  - Artificial transmembrane ion channels from self-assembling peptide nanotubes.
AB  - Naturally occurring membrane channels and pores are formed from a large family of
      diverse proteins, peptides and organic secondary metabolites whose vital
      biological functions include control of ion flow, signal transduction, molecular
      transport and production of cellular toxins. But despite the availability of a
      large amount of biochemical information about these molecules, the design and
      synthesis of artificial systems that can mimic the biological function of natural
      compounds remains a formidable task. Here we present a simple strategy for the
      design of artificial membrane ion channels based on a self-assembled cylindrical
      beta-sheet peptide architecture. Our systems--essentially stacks of peptide rings
      -display good channel-mediated ion-transport activity with rates exceeding 10(7)
      ions s-1, rivalling the performance of many naturally occurring counterparts.
      Such molecular assemblies should find use in the design of novel cytotoxic
      agents, membrane transport vehicles and drug-delivery systems.

PMID- 7514276
TI  - Translational regulation of nanos by RNA localization.
AB  - Localization of the maternally synthesized nanos (nos) RNA to the posterior pole
      of the Drosophila embryo provides the source for a posterior-to-anterior gradient
      of Nos protein. Correct spatial regulation of nos activity is essential for
      normal pattern formation. High local concentrations of Nos protein in the
      posterior of the embryo are necessary to inhibit translation of the transcription
      factor Hunchback in this region, and thus permit expression of genes required for
      abdomen formation (see ref. 5 for review). By contrast, misexpression of Nos
      protein at the anterior of the embryo prevents translation of the anterior
      morphogen Bicoid, suppressing head and thorax development. Posterior localization
      of nos RNA is mediated by sequences within the nos 3' untranslated region (3'UTR)
      and requires the function of eight genes of the 'posterior group'. Although the
      unlocalized nos RNA is stable in embryos from females mutant for any of the
      posterior group genes, these embryos appear to lack nos activity because they
      develop the abdominal defects characteristic of embryos produced by nos mutant
      females. We report here that unlocalized nos RNA is translationally repressed.
      Translational repression is mediated by the nos 3'UTR and can be alleviated
      either by replacement of the 3'UTR with heterologous 3'UTR sequences or by
      posterior localization. Thus, RNA localization provides a novel mechanism for
      translational regulation.

PMID- 7514278
TI  - [Variability of values of prostate-specific antigen determined with 6 methods].
AB  - OBJECTIVE: To illustrate the variability of serum Prostate Specific Antigen (PSA)
      and its causes in relevant clinical patient populations. SETTING: University
      Hospital Rotterdam, the Netherlands. DESIGN: Descriptive. METHODS: Six different
      methods of PSA analysis were applied to sera of 19 participants of a screening
      population, 20 patients after radical prostatectomy, and 15 newly diagnosed
      patients with a prostate carcinoma. The Hybritech Tandem-R value was chosen as
      the standard to compare the methods of analysis. Around a standard of 4.0
      micrograms/l a range of 3.3 to 7.2 micrograms/l was found; around 10.0
      micrograms/l a range of 8.7 to 18.5 micrograms/l. After radical prostatectomy the
      different methods of analysis agreed completely in only 5 out of 15 patients with
      respect to serum PSA. CONCLUSION: Because of a considerable variability in serum
      PSA values between different laboratories and methods of analysis, and of overlap
      between benign and malignant prostatic diseases, reference values of PSA should
      be handled with great care.

PMID- 7514277
TI  - Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate
      the signal for T-cell proliferation.
AB  - The interleukin-2 receptor (IL-2R) consists of three distinct chains (alpha,
      beta, gamma) which bind IL-2 and generate a proliferative signal in T cells. To
      define the mechanism of receptor activation, chimaeric receptors were constructed
      from the intracellular region of either IL-2R beta or IL-2R gamma and the
      extracellular region of c-kit, a receptor tyrosine kinase that homodimerizes on
      binding stem cell factor (SCF). We report here that binding of SCF to the beta
      chain chimaera induced proliferation of the pro-B-cell line BA/F3, but not T
      cells. But in T cells expressing both the beta- and gamma-chain chimaeras, SCF
      induced proliferation and tyrosine phosphorylation characteristic of the native
      IL-2R signal. Chimaeric IL-2 receptor beta and gamma chains constructed with the
      heterodimeric extracellular regions of the granulocyte-macrophage colony
      stimulating factor receptor (GM-CSFR) also provided the IL-2R signal. Thus,
      heterodimerization of the cytoplasmic domains of IL-2R beta and -gamma appears
      necessary and sufficient for signalling in T cells.

PMID- 7514279
TI  - Time-dependent changes in central nicotinic acetylcholine channel kinetics in
      excised patches.
AB  - The behavior of nicotinic acetylcholine receptor (nAChR) channels in acutely
      isolated habenula neurons was examined by rapidly applying nicotinic agonists to
      outside-out membrane patches. At negative membrane potentials, applications of
      100 microM nicotine routinely produced macroscopic currents due to the opening of
      a large number of channels. During the continuous application of the agonist, the
      number of open nAChR channels decreased exponentially, i.e. receptor
      desensitization. A progressive loss in the number of channels contributing to the
      peak current was observed with time following outside-out patch excision, i.e.
      receptor rundown. In addition to rundown there was a time-dependent increase in
      the rate of desensitization and a concomitant slowing in the rate of recovery
      from desensitization. The extent of rundown and the changes in desensitization
      were coupled to the time after patch excision and were not dependent on ligand
      activation of nicotinic channels.

PMID- 7514280
TI  - Blockade by MPTP of the nicotinic acetylcholine receptor channels in embryonic
      Xenopus muscle cells.
AB  - The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on nicotinic
      acetylcholine (ACh) receptor channels were studied in cultured myocytes of 1-day
      old Xenopus embryos. The amplitude and decay time of iontophoretic ACh-induced
      currents were reduced by MPTP in a concentration-dependent manner. The inhibitory
      action of MPTP was frequency-dependent, being enhanced by higher frequencies of
      stimulation at 7 and 30 Hz. Neither pargyline nor tranylcypromine affected the
      inhibitory effects of MPTP on ACh-induced currents. Single channel recordings
      showed that MPTP decreased the opening frequency, mean open time as well as the
      conductance of both low- and high-conductance ACh channels. These results suggest
      that the inhibitory actions of MPTP on ACh receptor channels in skeletal muscle
      may contribute to the depression of the nerve-evoked contraction of the mouse
      diaphragm as previously reported.

PMID- 7514282
TI  - Cell kinetic effects of granulocyte colony-stimulating factor on the sensitivity
      of nonlymphocytic leukemia cells to cytosine arabinoside.
AB  - We measured the percentage of proliferating cells in peripheral blood and bone
      marrow of patients with nonlymphocytic leukemia by flow cytometry and
      immunostaining with antibodies to proliferating cell nuclear antigen (PCNA) and
      Ki-67. We evaluated the effects of granulocyte colony-stimulating factor (G-CSF)
      on nonlymphocytic leukemia cells. The S phase cell ratio, PCNA positive cell
      ratio, and Ki-67 positive cell ratio were higher after culture with G-CSF than
      culture without G-CSF. The ratio of viable cells was lower after culture with G
      CSF followed by cytosine arabinoside (Ara-C) than culture with Ara-C alone. The
      number of clonogenic leukemic cells in methylcellulose was also smaller after
      culture with G-CSF followed by Ara-C than Ara-C alone. Our results suggest that
      the administration of G-CSF before induction chemotherapy enhances the
      sensitivity of antitumor agents against leukemic cells.

PMID- 7514281
TI  - Food deprivation increases brain nitric oxide synthase and depresses brain
      serotonin levels in rats.
AB  - We studied nitric oxide (NO) synthase activity and serotonin content in the
      diencephalon of 24 hr food deprived rats. NO synthase activity was significantly
      increased whereas serotonin levels together with those of tryptophan and 5
      hydroxyindoleacetic acid (5-HIAA) were reduced in food deprived rats when
      compared to control rats. NG-Nitro-L-arginine (L-NO Arg), an inhibitor of NO
      synthase, was used as a tool to study the role of NO in food deprivation. Twenty
      four hr food deprived male Sprague-Dawley rats were intraperitoneally (i.p.)
      administered L-NO Arg (12.5, 25 and 50 mg/kg) before food presentation. Control
      rats received a NaCl (0.9%) solution. Food consumption was monitored 1 and 2 hr
      after food presentation. L-NO Arg administration produced a dose-dependent
      reduction in food intake. Pretreatment with metergoline (2 mg/kg) but not with
      ritanserin (1 mg/kg) antagonized the anorectic effect of L-NO Arg. Moreover, in
      the diencephalon L-NO Arg significantly reduced NO synthase activity whereas it
      increased serotonin levels. Our data indicate that NO might have a physiological
      role in the regulation of food intake and suggest that brain NO may modulate the
      central serotoninergic system.

PMID- 7514283
TI  - Protein kinase C-dependent release of a functional whole extracellular domain of
      the mast cell growth factor (MGF) receptor by MGF-dependent human myeloid cells.
AB  - The mast cell growth factor (MGF) affects migration, proliferation and
      differentiation of erythroid and myeloid progenitor cells by binding to a
      transmembrane receptor tyrosine kinase encoded by the c-Kit proto-oncogene. By
      using MGF-dependent human myeloid cell lines (M-07e and TF-1), here we show that
      a Kit-related 100 kDa protein is associated with the cell but it undergoes
      release into the medium upon treatment with the tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C.
      Immunological analysis with a series of antibodies to Kit indicated that the
      released protein (p100Kit) contains the whole glycosylated extracellular portion
      of the transmembrane Kit protein (p145Kit). The secreted protein retained the
      ability to specifically bind MGF. Moreover, p100Kit was able to block the
      mitogenic effect of MGF on cultured M-07e cells, suggesting that the soluble
      protein may function as a physiological antagonist of MGF.

PMID- 7514285
TI  - Regulation of a non-selective cation channel of cultured porcine coronary artery
      smooth muscle cells by tyrosine kinase.
AB  - A non-selective cation channel was found in primary cultured porcine coronary
      artery smooth muscle cells. In patch-clamp studies in the cell-attached mode,
      this channel was activated by bath application of genistein, a specific inhibitor
      of tyrosine kinase, but not by daidzein, which is similar in structure to
      genistein but has no inhibitory effect on tyrosine kinase. This channel
      discriminated poorly between Na+ and K+ (permeability ratio PNa/PK = 1.03), and
      also transported Ca2+. The single-channel conductance measured with a pipette
      solution containing 150 mM Na+ was 139 +/- 24 pS (mean +/- SD, n = 5), and that
      for the inward current measured with 100 mM Ca2+ solution was 25 +/- 9 pS (n =
      3). This non-selective cation channel was also activated by staurosporine, a non
      specific protein kinase inhibitor, but not by H-7, an inhibitor of protein
      serine/threonine kinase. These results suggest that the activity of the non
      selective cation channel is negatively regulated by tyrosine kinase activity, and
      thus a decrease of the enzyme activity in porcine coronary artery smooth muscle
      cells may result in membrane depolarization and Ca2+ entry.

PMID- 7514286
TI  - Ba2+ and amiloride uncover or induce a pH-sensitive and a Na+ or non-selective
      cation conductance in transitional cells of the inner ear.
AB  - The membrane potential Vm the cytosolic pH (pHi), the transference numbers (t)
      for K+, Cl- and Na+/non-selective cation (NSC) and the pH-sensitivity of Vm were
      investigated in transitional cells from the vestibular labyrinth of the gerbil.
      Vm, pHi, tK+, tCl-, tNa+/NSC, and the pHi sensitivity of Vm were under control
      conditions were -92 +/- 1 mV (n = 89 cells), pHi 7.13 +/- 0.07 (n = 11
      epithelia), 0.87 +/- 0.02 (n = 22), 0.02 +/- 0.01 (n = 19), 0.01 +/- 0.01 (n =
      24) and -5 mV/pH unit (n = 13 cells/n = 11 epithelia), respectively. In the
      presence of 100 mumol/l Ba2+ the corresponding values were: -70 +/- 1 mV (n =
      32), pHi 7.16 +/- 0.08 (n = 6), 0.31 +/- 0.05 (n = 4), 0.06 +/- 0.01 (n = 6),
      0.20 +/- 0.03 (n = 10) and -16 mV/pH-unit (n = 15/n = 6). In the presence of 500
      mumol/l amiloride the corresponding values were: -72 +/- 2 mV (n = 34), pHi 7.00
      +/- 0.07 (n = 5), 0.50 +/- 0.04 (n = 6), 0.04 +/- 0.01 (n = 11), 0.28 +/- 0.04 (n
      = 9) and -26 mV/pH-unit (n = 20/n = 5). In the presence of 20 mmol/l propionate
      plus amiloride the corresponding values were: -61 +/- 2 mV (n = 27), pHi 6.72 +/-
      0.06 (n = 5), 0.30 +/- 0.02 (n = 6), 0.06 +/- 0.01 (n = 5) and 0.40 +/- 0.02 (n =
      8), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514284
TI  - The role of the inwardly rectifying K+ current in resting potential and
      thyrotropin-releasing-hormone-induced changes in cell excitability of GH3 rat
      anterior pituitary cells.
AB  - Exposure of GH3 rat anterior pituitary cells to cholera toxin for 2-4 h
      significantly increased the thyrotropin-releasing-hormone(TRH)-induced inhibition
      of the inwardly rectifying K+ current studied in patch-perforated voltage-clamped
      cells. On the other hand, the current reduction became almost totally
      irreversible after washout of the neuropeptide. Comparison of the effects
      elicited by the toxin with those of 8-(4-chlorophenylthio)-cAMP or forskolin plus
      isobutylmethylxanthine indicated that, although the irreversibility may be due,
      at least in part, to elevations of cAMP levels, the enhancement of the TRH
      induced inhibition of the current is not mediated by the cyclic nucleotide. Only
      reductions on the inwardly rectifying K+ current, but not those elicited by TRH
      on voltage-dependent Ca2+ currents, were increased by the treatment with cholera
      toxin. In current-clamped cells showing similar rates of firing, the second phase
      of enhanced action-potential frequency induced by TRH was also significantly
      potentiated by cholera toxin. Measurements of [Ca2+]i oscillations associated
      with electrical activity, using video imaging with fura-2-loaded cells,
      demonstrated that cholera toxin treatment causes a clear reduction of spontaneous
      [Ca2+]i oscillations. However, this did not prevent the stimulatory effect of TRH
      on oscillations due to the action potentials. In cholera-toxin-treated cells, the
      steady-state, voltage dependence of inactivation of the inward rectifier was
      shifted by nearly 20 mV to more negative values. These data suggest that the
      inwardly rectifying K+ current plays an important role in maintenance of the
      resting K+ conductance in GH3 cells. Furthermore, the TRH-induced reductions on
      this current may be an important factor contributing to the increased cell
      excitability promoted by the neuropeptide.

PMID- 7514287
TI  - Analysing ion channels with hidden Markov models.
AB  - Ion channel current amplitudes (mu) and open probabilities (Po) have been
      analysed so far by defining a 50% threshold to distinguish between open and
      closed states of the channels. With this standard method (SM) it is very
      difficult or even impossible to analyse channels of different size in one
      membrane patch correctly. A stochastical model, named the hidden Markov model
      (HMM), separates between observation noise and the stochastic process of opening
      and closing of ion channels. The HMM allows the independent analysis of mu, Po,
      and mean dwell times (tau) of different channels in one membrane patch, without
      defining threshold levels. Using this method errors in the analysis are not
      summarized like in the SM because all different analysing procedures (e.g.
      filtering, setting of threshold, fitting processes) are done in one step. Two
      different K+ channels in excised basolateral membranes of the cortical collecting
      duct of rat (CCD) were analysed by the SM and the HMM. The mu value of the
      intermediate-conductance K+ channel (i-K+) was 3.9 +/- 0.1 pA (SM) and 3.8 +/-
      0.2 pA (HMM) for 11 observations. The Po value of this channel was 10.2 +/- 4.2%
      (SM) and 10.1 +/- 4.0% (HMM). The mean tau values were 5.4 +/- 0.6 ms for the
      open state and 9.6 +/- 2.2 ms and 145 +/- 21 ms for the closed states (SM) and
      7.8 +/- 1.1 ms, 7.7 +/- 0.9 ms and 148 +/- 24 ms (HMM), respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7514288
TI  - Recent advances in cystic fibrosis.

PMID- 7514289
TI  - Implications of maternal serum alpha-fetoprotein elevation caused by
      transabdominal and transcervical CVS.
AB  - Of 2882 women allocated to either transabdominal CVS (TA) or transcervical CVS
      (TC) at two large obstetric centres in Denmark, 2707 had blood samples drawn
      before and 30 min after CVS for maternal serum-alpha-fetoprotein (MSAFP)
      measurement. 2535 of these women had cytogenetically normal pregnancies and 2091
      of them went on to have samples drawn at the 18-20 week follow-up. Post-procedure
      MSAFP values were correlated to the biopsy method used, with mean MSAFP values
      significantly higher after TA than TC, 33 and 15 kU/l, respectively (P < 0.001).
      Following TA procedures, 18 per cent of cases had feto-maternal transfusion
      higher than 0.1 ml; this occurred in only 5 per cent of TC cases. MSAFP levels
      were associated with spontaneous fetal loss in the TA group but not in the TC
      group. TC, however, was followed by more losses than TA. The post-CVS MSAFP value
      was positively correlated with the amount of villi aspirated. The difference in
      post-procedure elevation in MSAFP 30 min later (average 18 kU/l higher for TA
      than for TC) was not reflected in raised levels at the 18-20 week follow-up.
      Study medians at mid-trimester did not differ from reference group medians
      established from a group of singleton pregnancies with sonographically determined
      gestational age who did not experience invasive procedures and delivered normal
      infants. Our findings suggest that CVS does not compromise mid-trimester MSAFP
      for screening for neural tube defects (NTDs). Extremely high mid-trimester MSAFP
      values in the TC group could predict imminent loss.

PMID- 7514291
TI  - Maternal serum free beta hCG screening: results of studies including 480 cases of
      Down syndrome.
AB  - The median maternal serum free beta human chorionic gonadotropin (hCG) multiple
      of the median (MOM) of 480 Down syndrome cases in the second trimester was 2.64,
      significantly greater than the reported median MOM of intact hCG (p < 0.0001). In
      234 of these cases from retrospective and prospective studies, the effectiveness
      of maternal serum free beta hCG was evaluated in combination with alpha
      fetoprotein (AFP) and maternal age in second-trimester Down syndrome screening.
      Down syndrome detection in the gestational age range of 14-16 weeks was 82 per
      cent. In all gestational weeks (14-22), a 77.7 per cent Down syndrome detection
      rate was achieved. In prospective screening of 44,272 patients under the age of
      35 years, 69 per cent of Down syndrome cases were detected (73 per cent in
      gestational weeks 14-16). The false-positive rate for the prospective study was
      3.8 per cent. The use of free beta hCG combined with maternal serum AFP and
      maternal age-related risk for Down syndrome in a screening population (i.e.,
      women under 35 years) yields an improved detection efficiency over other
      protocols.

PMID- 7514290
TI  - Human chorionic gonadotropin and unconjugated oestriol measurements in insulin
      dependent diabetic pregnant women being screened for fetal Down syndrome.
AB  - This prospective study investigates the relationship between insulin-dependent
      diabetes and maternal serum levels of alpha-fetoprotein (AFP), unconjugated
      oestriol (uE3), and human chorionic gonadotropin (hCG). It also examines the
      potential impact on screening for Down syndrome. The population-based cohort
      included 20,321 pregnant women in Maine who underwent routine serum screening for
      Down syndrome in the second trimester. The cohort included 52 women with insulin
      dependent diabetes. Maternal serum AFP levels are now routinely adjusted for
      insulin-dependent diabetes. These adjustments, therefore, were made routinely in
      the diabetic women, but no equivalent adjustments were made for uE3 and hCG
      values. The initial false-positive rate (using all three markers) among the women
      with diabetes was not significantly different from that in the non-diabetic
      population (7.7 and 5.4 per cent, respectively). Prior to adjustment for insulin
      dependent diabetes, the median AFP level in the 52 women was 0.73 multiples of
      the median (MOM); the median levels of uE3 and hCG were 0.93 and 0.98 MOM,
      respectively. When the uE3 and hCG levels were adjusted, the initial false
      positive rate was unchanged. Median serum levels of uE3 were significantly higher
      in the 33 women whose onset of diabetes was prior to 19 years of age (0.99 MOM)
      than in the 19 women whose onset of diabetes was at age 19 or older (0.84 MOM).
      This is the first population-based study to investigate the relationship between
      diabetes and serum levels of AFP, uE3, and hCG, and confirms earlier observations
      from a case-control study that found only slightly lower uE3 and hCG levels.

PMID- 7514292
TI  - [Mucoviscidosis--3 years after discovery of the gene].
AB  - The discovery of the cystic fibrosis (cF) gene was the first step to evaluate the
      function of its product, the "cystic fibrosis transmembrane conductance
      regulator" protein and the regulation of this gene. CFTR is a cAMP-dependent CI(
      )-channel, which is defect in cF. In contrast, a second CI(-)-channel in
      epithelial cells is activated by increasing intracellular Ca++ and fully
      functional in cF cells. Increasing intracellular Ca++ not only activates the
      Ca(++)-dependent channel, but also downregulates the CFTR gene expression in the
      same epithelial cells, suggesting a feedback mechanism. This regulatory pathway
      is based on a protein kinase, probably protein kinase C. The results of this
      study are a prerequisite for a gene therapy in cF which demands intimate
      knowledge of the regulation of the CFTR gene. In addition, these results suggest
      different therapeutical strategies to circumvent the defect in cF cells, which is
      discussed in detail.

PMID- 7514293
TI  - [Circadian rhythm in allergic inflammation].
AB  - There are significant bioperiodicities for hormonal, neural, cellular, and
      humoral factors as well as for mediators. A combination of these findings is an
      explanation for the increased hyperreactivity in patients with allergic diseases
      during the night. In the morning hours between 2 and 6 a.m., the histamine
      concentration shows a peak, adrenaline and cyclic AMP have their minimum, while
      cortisol secretion is just ascending. Circadian variations are also seen with
      respect to the density of beta-receptors. Thromboxane A2 shows a peak during the
      night, PGE2 is depressed, a finding also in favour of bronchial constriction.
      Total plasma protein IgA, IgM, IgG and IgE show a distinct bioperiodicity with a
      minimum during the night, cellular elements like T11, T4 and B-lymphocytes, and
      Leu8 have a maximum. The nocturnal symptom exacerbation must be given the fullest
      attention in choosing the time of administration of the appropriate medication.

PMID- 7514294
TI  - Stem-loop IV of 5S rRNA lies close to the peptidyltransferase center.
AB  - A DNA fragment containing the Escherichia coli 5S rDNA sequence linked to a T7
      promoter was prepared by PCR from an M13 clone carrying the 5S-complementary
      sequence. The DNA was transcribed with T7 polymerase using a mixture of [alpha
      32P]UTP and 4-thio-UTP, yielding a transcript in which approximately 18% of the
      uridine residues were randomly replaced by thiouridine. This modified 5S RNA
      could be reconstituted efficiently into 50S ribosomal subunits or 70S functional
      complexes. The reconstituted particles were irradiated at wavelengths above 300
      nm, and the crosslinked ribosomal components were identified. A crosslink in high
      yield was reproducibly observed between the modified 5S RNA and 23S RNA,
      involving residue U-89 of the 5S RNA (at the loop end of helix IV) linked to
      nucleotide 2477 of the 23S RNA in the loop end of helix 89, immediately adjacent
      to the peptidyltransferase "ring." On the basis of this result, and in
      combination with earlier immunoelectron microscopic data, we propose a model for
      the orientation of the 5S RNA in the 50S subunit.

PMID- 7514295
TI  - Rapid T-cell receptor-mediated tyrosine phosphorylation of p120, an Fyn/Lck Src
      homology 3 domain-binding protein.
AB  - Tyrosine phosphorylation of cellular proteins is the earliest identifiable event
      following T-cell antigen receptor (TCR) stimulation and is essential for
      activating downstream signaling machinery. Two Src-family protein-tyrosine
      kinases, the TCR-associated p59fyn (Fyn) and the CD4/8-associated p56lck (Lck),
      have emerged as the likely mediators of early tyrosine phosphorylation in T
      cells. Here, we show direct binding of a 120-kDa TCR-induced phosphotyrosyl
      polypeptide, p120, to glutathione S-transferase fusion proteins of the Src
      homology 3 (SH3) domains of Fyn, Lck, and p60src (Src) but not other proteins.
      While binding of p120 to Fyn SH2 domain was phosphotyrosine-dependent as
      expected, its binding to the SH3 domain was independent of tyrosine
      phosphorylation, as shown by lack of competition with a phosphotyrosyl competitor
      peptide. In contrast, an SH3-specific proline-rich peptide completely abolished
      p120 binding to SH3. p120 was tyrosine-phosphorylated within 10 sec following
      stimulation of Jurkat cells with anti-CD3 monoclonal antibody, with maximal
      phosphorylation at 30 sec. Importantly, p120 was found associated with Fyn and
      Lck proteins in unstimulated Jurkat cells and served as an in vitro substrate for
      these kinases. These results provide evidence for a role of the SH3 domains of
      Fyn and Lck in the recruitment of early tyrosine-phosphorylation substrates to
      the TCR-associated tyrosine kinases.

PMID- 7514296
TI  - Structure of a mispaired RNA double helix at 1.6-A resolution and implications
      for the prediction of RNA secondary structure.
AB  - The nonamer r(GCUUCGGC)dBrU, where dBrU is 5-bromo-2'-deoxyuridine, contains the
      tetraloop sequence UUCG. It crystallizes in the presence of Rh(NH3)6Cl3. In
      solution the oligomer is expected to form a hairpin loop but the x-ray structure
      analysis, to a resolution of 1.6 A, indicates an eight-base-pair A-RNA duplex
      containing a central block of two G.U and two C.U pairs. Self-pairs which
      approximate to Watson-Crick geometry are also formed in the extended crystal
      structure between symmetry-related BrU residues and are part of infinite double
      helical stacks. The G.U pair is a wobble base pair analogous to the G.T pair
      found in DNA fragments. The C.U mismatch involves one hydrogen-bonded contact
      between the bases and a bridging water molecule which ensures a good fit of the
      base pair in the RNA helix. The BrU.BrU pair is held by two hydrogen bonds in an
      orientation which is compatible with duplex geometry. The structure observed
      within the crystal has some parallels with the structure of globular RNAs, and
      the presence of stable, noncanonical base pairs has implications for the
      prediction of RNA secondary structure.

PMID- 7514297
TI  - Participation of target Fas protein in apoptosis pathway induced by CD4+ Th1 and
      CD8+ cytotoxic T cells.
AB  - The results presented here provide evidence that the presence of Fas protein in
      target cells is essential to permit cytotoxicity (resulting in apoptosis)
      mediated by cloned CD4+ Th1 cells. Using mitogen-activated B cells as targets,
      antigen-dependent lysis by CD4+ Th1 effectors was observed with MRL/MpJ+ but not
      with MRL/MpJ-lpr targets. The congenic MRL/MpJ-lpr strain is defective in Fas
      expression. Target cells from various lymphoid tissues of C3H.MRL-lpr mice were
      also resistant to the lectin-dependent cytotoxicity of Th1 effectors, whereas
      C3H/HeJ targets were sensitive. Moreover, a rapid DNA fragmentation prior to 51Cr
      release was induced only in C3H/HeJ targets. Thus, cytotoxicity induced by Th1
      effectors correlates with target Fas expression. In contrast to Th1 effectors,
      CD8+ cytotoxic T lymphocytes (CTLs) killed C3H.MRL-lpr targets. When cytotoxicity
      was assayed in the presence of EGTA and MgCl2, which chelates extracellular Ca2+
      [(Ca2+)ext], only C3H.MRL-lpr targets became resistant to CD8+ CTLs. This
      (Ca2+)ext-independent cytotoxicity of both Th1 and CD8+ effectors could be
      inhibited with unlabeled C3H/HeJ thymocytes or with a transfectoma carrying a
      murine Fas-human mu gene construct. In comparison, C3H.MRL-lpr thymocytes and the
      nontransfected parental cell line were poor inhibitors. Our study demonstrates
      that CD4+ Th1 cells and CD8+ CTLs differ in their (Ca2+)ext-dependent
      cytotoxicity but share a (Ca2+)ext-independent cytotoxicity that requires
      participation of Fas molecules for cytotoxic signal transduction leading to
      target apoptosis.

PMID- 7514298
TI  - Production of angiogenic activity by human monocytes requires an L
      arginine/nitric oxide-synthase-dependent effector mechanism.
AB  - Human monocytes (M phi) require stimulation with substances such as bacterial
      endotoxin [LPS (lipopolysaccharide)] to produce angiogenic activity. In this
      study, we report that stimulation of M phi with LPS (5 micrograms/ml) in the
      absence of L-arginine greatly reduced their production of angiogenic activity, as
      assessed in vivo in rat corneas and in vitro by chemotaxis of human umbilical
      vein endothelial cells (HU-VECs). D-Arginine did not substitute for L-arginine in
      the production of angiogenic activity. The nitric oxide synthase (NO synthase, EC
      1.14-13.39) inhibitors NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine
      methyl ester (L-NAME) both inhibited the production of angiogenic activity by LPS
      stimulated M phi in the presence of L-arginine, suggesting the involvement of
      this enzyme in the pathway that generates angiogenic activity. Neither of these
      substances directly inhibited the M phi-derived angiogenic activity. LPS-induced
      production of the cytokines tumor necrosis factor alpha (TNF-alpha) and
      interleukin 8 (IL-8) was not significantly reduced when M phi were incubated in
      the absence of L-arginine. Similarly, L-NMMA and L-NAME did not significantly
      reduce the LPS-induced production of these cytokines by M phi in the presence of
      L-arginine. These results suggest that the LPS-stimulation-dependent generation
      of angiogenic activity by M phi requires an L-arginine-dependent NO-synthase
      effector mechanism that may be independent of the generation of TNF-alpha and IL
      8.

PMID- 7514299
TI  - Tyrosine phosphorylation of Blk and Fyn Src homology 2 domain-binding proteins
      occurs in response to antigen-receptor ligation in B cells and constitutively in
      pre-B cells.
AB  - Proteins that bind to discrete domains of the Blk, Fyn, Lyn, and Btk protein
      tyrosine kinases were examined in pre-B cells that had not been subjected to any
      external stimulation, as well as in nonstimulated and antigen-receptor-ligated B
      cells. Proteins that bind to the Src homology 2 domains of Blk and Fyn were
      identified in B cells that had been activated with anti-IgM but were not
      identified in unstimulated B cells. A number of Blk and Fyn Src homology 2 domain
      binding phosphoproteins were also observed in pre-B cells that had not been
      stimulated in vitro. The phosphoproteins seen in activated B cells potentially
      represent substrates that play a role in the pathway of antigen-receptor-mediated
      signaling. Distinct signaling pathways involving distinguishable kinase
      substrates may be relevant in pre-B-cell-receptor-mediated cell survival during
      ontogeny. These results indirectly support models that predict constitutive
      ligand-independent signaling by the pre-antigen receptor during lymphoid
      ontogeny.

PMID- 7514301
TI  - The 58-kilodalton inhibitor of the interferon-induced double-stranded RNA
      activated protein kinase is a tetratricopeptide repeat protein with oncogenic
      properties.
AB  - The interferon-induced RNA-dependent protein kinase (PKR) is considered to play
      an important role in the cellular defense against viral infection and, in
      addition, has been suggested to be a tumor suppressor gene because of its growth
      suppressive properties. Activation of PKR by double-stranded RNAs leads to the
      phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2
      alpha) and a resultant block to protein synthesis initiation. To avoid the
      consequences of kinase activation, many viruses have developed strategies to down
      regulate PKR. Recently, we reported on the purification and characterization of a
      cellular inhibitor of PKR (referred to as p58), which is activated during
      influenza virus infection. Subsequent cloning and sequencing has revealed that
      p58 is a member of the tetratricopeptide repeat (TPR) family of proteins. To
      further examine the physiological role of this PKR inhibitor, we stably
      transfected NIH 3T3 cells with a eukaryotic expression plasmid containing p58
      cDNA under control of the cytomegalovirus early promoter. By taking advantage of
      a recently characterized p58 species-specific monoclonal antibody, we isolated
      cell lines that overexpressed p58. These cells exhibited a transformed phenotype,
      growing at faster rates and higher saturation densities and exhibiting anchorage
      independent growth. Most importantly, inoculation of nude mice with p58
      overexpressing cells gave rise to the production of tumors. Finally, murine PKR
      activity and endogenous levels of eIF-2 alpha phosphorylation were reduced in the
      p58-expressing cell lines compared with control cells. These data, taken
      together, suggest that p58 functions as an oncogene and that one mechanism by
      which the protein induces malignant transformation is through the down-regulation
      of PKR and subsequent deregulation of protein synthesis.

PMID- 7514300
TI  - Endothelial nitric oxide synthase localized to hippocampal pyramidal cells:
      implications for synaptic plasticity.
AB  - Using antibodies that react selectively with peptide sequences unique to
      endothelial nitric oxide synthase (eNOS), we demonstrate localizations to
      neuronal populations in the brain. In some brain regions, such as the cerebellum
      and olfactory bulb, eNOS and neuronal NOS (nNOS) occur in the same cell
      populations, though in differing proportions. In the hippocampus, localizations
      of the two enzymes are strikingly different, with eNOS more concentrated in
      hippocampal pyramidal cells than in any other brain area, whereas nNOS is
      restricted to occasional interneurons. In many brain regions NADPH diaphorase
      staining reflects NOS catalytic activity. Hippocampal pyramidal cells do not
      stain for diaphorase with conventional paraformaldehyde fixation but stain
      robustly with glutaraldehyde fixatives, presumably reflecting eNOS catalytic
      activity. eNOS in hippocampal pyramidal cells may generate the NO that has been
      postulated as a retrograde messenger of long-term potentiation.

PMID- 7514302
TI  - Evidence for a peripheral olfactory memory in imprinted salmon.
AB  - The remarkable homing ability of salmon relies on olfactory cues, but its
      cellular basis is unknown. To test the role of peripheral olfactory receptors in
      odorant memory retention, we imprinted coho salmon (Oncorhynchus kisutch) to
      micromolar concentrations of phenyl ethyl alcohol during parr-smolt
      transformation. The following year, we measured phenyl ethyl alcohol responses in
      the peripheral receptor cells using patch clamp. Cells from imprinted fish showed
      increased sensitivity to phenyl ethyl alcohol compared either to cells from naive
      fish or to sensitivity to another behaviorally important odorant (L-serine).
      Field experiments verified an increased behavioral preference for phenyl ethyl
      alcohol by imprinted salmon as adults. Thus, some component of the imprinted
      olfactory homestream memory appears to be retained peripherally.

PMID- 7514304
TI  - Anergic self-reactive B cells present self antigen and respond normally to CD40
      dependent T-cell signals but are defective in antigen-receptor-mediated
      functions.
AB  - B-cell tolerance to soluble protein self antigens such as hen egg lysozyme (HEL)
      is mediated by clonal anergy. Anergic B cells fail to mount antibody responses
      even in the presence of carrier-primed T cells, suggesting an inability to
      activate or respond to T helper cells. To investigate the nature of this defect,
      B cells from tolerant HEL/anti-HEL double-transgenic mice were incubated with a
      membrane preparation from activated T-cell clones expressing the CD40 ligand.
      These membranes, together with interleukin 4 and 5 deliver the downstream antigen
      independent CD40-dependent B-cell-activating signals required for productive T-B
      collaboration. Anergic B cells responded to this stimulus by proliferating and
      secreting antibody at levels comparable to or better than control B cells.
      Furthermore, anergic B cells presented HEL acquired in vivo and could present the
      unrelated antigen, conalbumin, targeted for processing via surface IgD. In
      contrast, the low immunoglobulin receptor levels on anergic B cells were
      associated with reduced de novo presentation of HEL and a failure to upregulate
      costimulatory ligands for CD28. These defects in immunoglobulin-receptor-mediated
      functions could be overcome in vivo, suggesting a number of mechanisms for
      induction of autoantibody responses.

PMID- 7514303
TI  - An epitope on carcinoembryonic antigen defined by the clinically relevant
      antibody PR1A3.
AB  - The monoclonal antibody PR1A3 has been used successfully for in vivo imaging of
      colorectal cancers, and several properties associated with this antibody,
      including minimal reactions of the antibody with circulating antigen in patients'
      sera, differentiate it from anti-carcinoembryonic antigen (CEA) antibodies used
      in similar studies. However, the antigen bound by PR1A3 was identified as CEA by
      analysis of somatic cell hybrids and by antigen expression from yeast artificial
      chromosomes, cosmids, and cDNA clones. The molecular weight, presence of a
      glycosyl-phosphatidylinositol anchor, elevation of surface expression by gamma
      interferon, and N-terminal amino acid sequence all confirmed the antigen
      identification as CEA. A series of biliary glycoprotein-CEA hybrid proteins was
      produced which demonstrated that the epitope bound by the antibody was at the
      site of membrane attachment and involved parts of the glycosyl
      phosphatidylinositol anchor and the B3 domain of CEA to form a conformational
      epitope. Access to this epitope, although possible when the antigen was on the
      cell surface, appeared to be blocked when CEA was released from the cell. The
      nature and location of the epitope on CEA are proposed to be responsible for the
      unique properties of the antibody.

PMID- 7514307
TI  - Response of bromodeoxyuridine-substituted Chinese hamster cells to UVA light
      exposure in the presence of Hoechst dye #33258: survival and DNA repair studies.
AB  - Previous work has established that DNA double-strand breaks (DSBs) are formed
      when Chinese hamster cells are substituted with 5-bromo-2'-deoxyuridine (BrdU)
      and exposed to UVA light in the presence of Hoechst dye #33258. Double-strand
      breaks produced by this treatment (5.1 x 10(-6) DSBs/BrdU residue/kJ m-2) were
      found to depend linearly on the level of BrdU substitution, Hoechst dye and
      fluence of UVA light. To examine the biological consequences of these novel DSBs,
      clonogenic assays were used to score cell survival, and elution assays were used
      to measure strand break levels at various times after photolysis. Using this
      system, marked cell killing was observed; photosensitivity could be increased by
      four orders of magnitude compared to cells without BrdU and dye. Decreases in the
      F0 value and the shoulder of survival curves followed increasing levels of BrdU
      substitution. In addition, the results indicate that DSBs produced by this
      photolysis protocol are two to three times more effective in causing cell killing
      than the DSBs produced by the action of ionizing radiation. To investigate the
      cause of the toxicity, repair of DSBs after photolysis was measured.
      Unexpectedly, DSB levels increased two- to threefold over 1 h at 37 degrees C,
      then decreased to initial damage levels over the next 2 h. The implications of
      this break induction are discussed in terms of mechanism and cell killing.

PMID- 7514305
TI  - Identification of a nonsense mutation in the granulocyte-colony-stimulating
      factor receptor in severe congenital neutropenia.
AB  - Severe congenital neutropenia (Kostmann syndrome) is characterized by profound
      absolute neutropenia and a maturation arrest of marrow progenitor cells at the
      promyelocyte-myelocyte stage. Marrow cells from such patients frequently display
      a reduced responsiveness to granulocyte-colony-stimulating factor (G-CSF). G-CSF
      binds to and activates a specific receptor which transduces signals critical for
      the proliferation and maturation of granulocytic progenitor cells. Here we report
      the identification of a somatic point mutation in one allele of the G-CSF
      receptor gene in a patient with severe congenital neutropenia. The mutation
      results in a cytoplasmic truncation of the receptor. When expressed in murine
      myeloid cells, the mutant receptor transduced a strong growth signal but, in
      contrast to the wild-type G-CSF receptor, was defective in maturation induction.
      The mutant receptor chain may act in a dominant negative manner to block
      granulocytic maturation.

PMID- 7514308
TI  - The serum prostate-specific antigen level three months after radiotherapy for
      prostate cancer: an early indicator of response to treatment.
AB  - A total of 347 patients with stages A2-C adenocarcinoma of the prostate treated
      with external beam radiotherapy and with pretreatment and 3-month prostate
      specific antigen (PSA) levels were studied to evaluate the potential prognostic
      significance of the fall in PSA concentration from its baseline (PSAB) to its 3
      month (PSA3) level. PSA levels fell in 333 patients (96%). With two exceptions,
      the patients whose PSA level did not fall had low PSAB and remained without
      evidence of disease. Since PSA levels fall virtually always, the fact that a fall
      occurs is of no prognostic value. When the magnitude of the fall relative to
      baseline was examined, patients with the largest falls had the worst outcomes.
      This paradoxical result was explained by the relationship between PSAB and PSA3.
      Regression analysis showed that the fall in PSA level was approximately
      proportional to the cube root of the baseline value. Thus, patients with high
      PSAB had high falls, but a high PSAB was an overwhelming predictor for poor
      outcome. Hence, PSA fall relative to baseline was not a meaningful prognostic
      factor. The only factor of prognostic value was the absolute PSA3 value. Patients
      with PSA3 < or = 2 ng/ml fared well at 4 years (freedom from relapse, 91%;
      incidence of rising PSA profile, 20%); patients with PSA3 > 2, but < or = 10
      ng/ml had an intermediate, individually indeterminate outcome (freedom from
      relapse, 51%; incidence of rising PSA profile, 58%); patients with PSA3 > 10
      ng/ml can be said to have failed treatment (freedom from relapse, 50%; incidence
      of rising PSA profile, 90%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514306
TI  - Alternatively spliced isoforms of the putative renal Na-K-Cl cotransporter are
      differentially distributed within the rabbit kidney.
AB  - We have used cDNA probes derived from the secretory form of the Na-K-Cl
      cotransporter to screen both cortical and medullary rabbit kidney cDNA libraries.
      A sequence of 4750 bases was identified from multiple clones. The DNA encodes a
      protein containing 1099 amino acids, which is 61% identical over its length to
      the secretory Na-K-Cl cotransporter from shark rectal gland. From analysis of
      amino acid hydropathy, we predict that this putative renal Na-K-Cl cotransporter
      has 12 transmembrane helices and large N- and C-terminal cytoplasmic regions. Two
      sites for N-linked glycosylation are predicted on an extracellular loop. Three
      potential sites for modulation by protein kinase A are in the C-terminal
      cytoplasmic domain. Most of the isolated renal cDNA clones were identical over
      all regions of overlap; however, there was a 96-bp region for which there were
      three different but homologous variants (A, B, and F). This region of divergence
      was identified as an alternatively spliced cassette exon since clones were
      identified that contained intronic DNA as well as consensus splice acceptor sites
      that bounded the region. Tissue Northern blot analysis revealed a broad band at
      approximately 5.1 kb that was unique to the kidney. High-stringency Northern blot
      analysis of cortical and medullary mRNA using antisense oligonucleotides
      synthesized over each of the three cassette exons revealed that the isoforms were
      differentially distributed within the kidney--B almost exclusively in cortex, F
      almost exclusively in medulla, and A about equally distributed.

PMID- 7514309
TI  - Urinary enzymes as biomarkers of renal injury in experimental nephrotoxicity of
      immunosuppressive drugs.
AB  - Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and of alanine
      aminopeptidase (AAP) was studied after administration of cyclosporine A (CSA A),
      FK 506, or the corresponding vehicles to salt-depleted rats. On days 7, 14, and
      28 after treatment for CSA and day 14 after treatment for FK 506, measurements of
      the urinary enzymes, serum creatinine (SCr), creatinine clearance (ClCr), and
      blinded renal histology were done. After 1 week on CSA there was a dramatic
      increase of 489% in the urinary excretion of AAP (162.6 IU/g Cr, CSA vs. 27.6
      IU/g Cr control, p < .03), a significant decrease of 32% in ClCr, a significant
      increase of 41% in SCr, and mild proximal tubular atrophy and vacuolization.
      After 2 or 4 weeks of CSA treatment there were no more differences in the urinary
      AAP between CSA and control rats, but the urinary excretion of NAG was increased:
      29.6 IU/g Cr, CSA vs. 20.9 IU/g Cr, control, p < .03 on day 14 and 26.9 IU/g Cr,
      CSA vs. 21.5 IU/g Cr, control, p < .008 on day 28. At the same time there was a
      progressive decline of the ClCr, a progressive increase in the SCr, and an
      increase in the severity of the histological lesion. After 14 days of treatment
      with FK 506 we observed a striking elevation in urinary AAP (62.6 IU/g Cr, FK 506
      vs. 36.0 IU/g Cr, control, p < .01) consistent with a significant decrease in
      ClCr, a significant increase in SCr, and a moderate proximal tubular
      vacuolization and atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514310
TI  - Sepsis and acute renal failure.

PMID- 7514311
TI  - [The evolution of serologic tests in the diagnosis of HCV infections].
AB  - The Authors take in account the technical aspects of the serological tests for
      the diagnosis of HCV infections. Particularly they consider the better diagnostic
      capacity of the 2nd generation and, at the present time, 3rd generation screening
      tests compared to tests of 1st generation. This happens because an antigen, the
      c33-c, codified by a genomic sequence, specific for the non-structural proteins,
      NS3, of the genome of HCV virus is used in the last methodologies. This antigen
      induces the production of specific antibodies more quickly than the other
      antigenic proteins. Moreover in many cases of HCV infections it has been
      evidenced that the anti-c33-c are the only antibodies produced. For this reason
      the tests that use this antigen not only allow an early diagnosis, enclosing the
      "window effect", but in every case have the best diagnostic capacity. Moreover
      the authors evaluate also the tests defined "confirmatory tests", in which the
      importance of the presence of systems for the identification of both anti-c33-c
      and c22-3 antibodies is evidenced.

PMID- 7514312
TI  - Biological role of alpha-fetoprotein in the endocrinological field: data and
      hypotheses.
AB  - alpha-Fetoprotein (AFP), depending on the surrounding conditions, exerts
      different functions by different mechanisms. (1) A regulatory effect on the
      concentration of the unbound form of its various ligands (e.g. fatty acids,
      estrogens, phytosteroids). Thus, numerous studies have demonstrated that fatty
      acids, particularly the polyunsaturated fatty acids, modulate positively or
      negatively many steps of the action of various steroids and many enzymes involved
      in the transduction of membrane-triggered signals. (2) Different conformations
      (holoforms) of AFP, depending on the nature and concentration of the ligand(s)
      bound, might influence the binding of the protein to specific receptor(s) and as
      a consequence its biological properties (internalization, action on the membrane
      signal transduction pathway). (3) Regardless of the mechanisms, proposed in
      points 1 and 2, the protein can exert effects associated with other signals such
      as growth factors. The nature of the associated growth factor(s) and AFP
      ligand(s) can orient cells towards multiplication or differentiation.

PMID- 7514313
TI  - Are bereaved family members a valid proxy for a patient's assessment of dying?
AB  - OBJECTIVE: To compare assessments made retrospectively by bereaved family members
      (or the nearest carer to the patient) with assessments made before death by
      palliative staff and, where available, by patients themselves or the family
      member. METHODS: SETTING--two palliative care support teams. ASSESSMENTS--were
      recorded prospectively by team staff, patients and their family members for
      consecutive patients referred, and then were recorded retrospectively by family
      members during interview seven months after bereavement. MEASURES--seven items
      each rated 0 (best) to 4 (worst) using standard definitions. The rater was asked
      to average the severity over one week. ANALYSIS--ratings were tested for
      percentage agreement, for Cohen's Kappa (which controls for chance agreement) and
      for Spearman correlations. RESULTS: Staff ratings and family members'
      retrospective ratings, which described the last week of life, were available for
      35 patients. Six patients and seven family members had also been interviewed
      shortly before the patient's death. The main problems identified by all raters
      were similar: family anxiety, symptom control, patient anxiety and pain control.
      For three items, practical aid, wasted time and communication, agreement was good
      -all cases except one were equal or within one score. However, problems were
      rarely identified for these items. For the other four items: pain control, other
      symptom control, family anxiety and patient anxiety, there was little agreement,
      Cohen's Kappa ranged 0.05-0.22. Agreement for one item (patient anxiety) was
      significantly improved if a patient had died at home. Comparison of ratings made
      by the family members before the death and seven months after bereavement
      suggests that family members alter their assessments during bereavement.
      CONCLUSION: Retrospective assessments by bereaved family members may be valid for
      some items related to service provision, but not as the sole assessment of a
      patient's pain, symptoms or anxiety. We suggest that studies which rely on these
      retrospective ratings should assess the validity of their responses and record
      more information about the mood and grief of the family member.

PMID- 7514314
TI  - Taxol and embryonic development in the chick.
AB  - Taxol, an inhibitor of microtubule disassembly, is currently under investigation
      in the therapy of several human cancers. The current investigation was undertaken
      to characterize potential taxol developmental toxicity in chicks. On one of days
      1-4 of incubation, taxol was administered in dimethylsulfoxide (DMSO) or olive
      oil in a range of doses, the highest of which produced a high incidence of early
      embryo death. Production of gross structural malformations was sporadic and
      occurred in vehicle-treated as well as taxol-treated embryos. A more common
      manifestation of taxol toxicity was a syndrome of visceral abnormalities,
      including regression of the vitelline circulation, dilatation of the atria, and
      hemorrhage in the left side of the head and thorax, often with decreased eye
      pigmentation. Regardless of the day of treatment, this syndrome occurred at 4.5-5
      days. To investigate the possibility that taxol induced its effect through
      disruption of angiogenesis in the vitelline circulation, filters soaked in taxol
      were applied to the margin of the germ disc. No inhibition of vessel development
      was demonstrated. We conclude that taxol decreases the viability of embryos and
      that this impairment of survival precludes the development of birth defects.
      Solvent toxicity is an important confounder in the investigation of taxol
      embryotoxicity.

PMID- 7514315
TI  - Production of a human monoclonal antibody to a synthetic peptide by active in
      vivo immunization using a SCID mouse grafted with human lymphocytes.
AB  - In order to meet the present increased demands, we have tried to improve the
      methods to produce human monoclonal antibodies by using a SCID mouse grafted with
      human mononuclear cells. Initially, we gave an anti-asialo GM1 antibody to a SCID
      mouse to suppress the NK activity, as a pretreatment. Then, fifty million human
      mononuclear cells (MNC) from a healthy volunteer were injected intraperitoneally
      to the SCID mouse so as to construct a human immune system in the mouse (PBL-SCID
      mouse). We immunized the mouse with a synthetic peptide (pep 190) conjugated with
      KLH four times. The spleen cells taken from the immunized PBL-SCID mouse were
      fused with (mouse x human) heteromyeloma cells. The hybridoma cells were selected
      in GIT medium containing HAT and IL-6. Among 68 hybridoma-growing wells, we
      obtained one hybridoma clone (#41-1-4) which secreted a specific antibody to pep
      190. The reactivity of this monoclonal antibody was tested by ELISA and the
      specificity of this antibody was confirmed by an absorption test with different
      kinds of proteins. This paper is the first report of the successful production of
      peptide-specific human monoclonal antibody by active in vivo immunization using a
      PBL-SCID mouse. By this active in vivo immunization system using a PBL-SCID
      mouse, human monoclonal antibodies for any sort of peptide antigens may easily be
      made available.

PMID- 7514316
TI  - Effect of lead acetate on nitrite production by murine brain endothelial cell
      cultures.
AB  - One of the mechanisms by which lead may cause a perturbation in the nervous
      system is the alteration of endothelial cell function. This study investigated
      the effect of lead acetate on constitutive and cytokine-induced production of
      nitrite, a marker of nitric oxide, in brain microvascular endothelial cells.
      Nitric oxide synthase may be a target for lead and changes in its function can
      result in a cascade of physiological effects seen in vivo. Concentrations of 10,
      100, and 1000 nM lead acetate, in the presence or absence of 100 ng
      lipopolysaccharide/ml, 400 U interferon-gamma/ml and 100 U tumor necrosis factor
      alpha/ml, were added to confluent cultures of brain microvascular endothelial
      cells. Concentrations of lead acetate as low as 10 nM decreased constitutive
      levels of nitrite by 50% without inhibiting the inducible levels. Addition of 1
      microM lead acetate had no effect on [3H]L-leucine incorporation, lactate
      dehydrogenase release, or cellular morphology, indicating that the effect was
      selective. Increasing the concentration of extracellular calcium to 2 mM
      abolished the inhibitory effect of lead acetate on the constitutive production of
      nitrite. These studies suggest that low concentrations of lead are capable of
      inhibiting nitrite produced by the calcium-dependent constitutive form of nitric
      oxide synthase while the calcium-independent, inducible form of nitric oxide
      synthase is not affected. These data provide another testable hypothesis for the
      as yet undetermined mechanisms of lead neurotoxicity.

PMID- 7514317
TI  - Serum lipid changes in liver transplant recipients in a prospective trial of
      cyclosporine versus FK506.

PMID- 7514318
TI  - 1994 Receptor and Ion Channel Nomenclature.

PMID- 7514319
TI  - Antibody responses to HIV-1 envelope and gag epitopes in HIV-1 seroconverters
      with rapid versus slow disease progression.
AB  - We studied the relationship between the rate of disease progression after HIV-1
      seroconversion and the level of IgG antibody response to HIV-1 envelope and core
      epitopes. This was done by comparing a group of fast-progressing individuals and
      a group of slow-progressing individuals for serum IgG titers to peptides from the
      gp120-V3 neutralization domain, to a peptide from the immunodominant gp41 epitope
      (residues 590 to 607), and to recombinant gp120 and p24. The two groups displayed
      a large overlap in titers to the envelope epitopes, which precluded their
      differentiation at most time points after seroconversion. Low responsiveness to
      envelope antigens was not only found in a few fast-progressors but also in one
      individual who remained asymptomatic for at least 92 months after seroconversion.
      The only significant differences between the groups were found in the first
      months after seroconversion when the responses to the V3 domain and the gp41
      epitope were more vigorous in the group of fast-progressors. Furthermore, on
      evaluating ratios of anti-V3 antibody titers to anti-gp120 antibody titers we
      found no indication that fast disease progression was associated with a
      restriction in antibody response to the V3 epitope. We did confirm the finding
      that fast disease progression is associated with low levels of p24-directed
      antibodies, both early after seroconversion and at later stages. These data
      demonstrate that levels of IgG antibodies to envelope epitopes are poor
      predictors of rapid disease progression and suggest that the role of V3-directed
      neutralizing antibodies in preventing subversion of the immune system is not
      decisive in natural HIV-1 infection.

PMID- 7514320
TI  - Characterization of a human astrovirus serotype 2 structural protein (VP26) that
      contains an epitope involved in virus neutralization.
AB  - An improved purification procedure for human astrovirus serotype 2 (H-Ast2) has
      facilitated the isolation of a neutralizing monoclonal antibody (PL-2) directed
      against one of the major structural proteins (VP26) of H-Ast2. A minor component
      (VP29) of the virus particles is also recognized by PL-2 antibody.
      Immunofluorescent staining indicated that VP26 (and/or VP29) has mainly a
      cytoplasmic location in LLCMK2-infected cells. Immunoelectron microscopy
      demonstrated that the PL-2 epitope was present in the surface of astrovirus
      particles. Pulse-chase radiolabeling and immunoprecipitation of H-Ast2-infected
      cell extracts identified a P86 precursor of VP26. Several intermediate protein
      species (P74 to P35) that shared the PL-2 epitope were also identified in the
      infected cells. Finally, partial N-terminal sequencing of VP29 and VP26
      polypeptides demonstrated that they originated by alternative processing of P86
      after residues 361 and 394, respectively. These results corroborate the location
      of the astrovirus structural genes at the 3' end of the viral genome included in
      the previously identified 2.8-kb subgenomic RNA.

PMID- 7514321
TI  - Serological and genomic characterization of equine rotavirus VP4 proteins
      identifies three different P serotypes.
AB  - A series of viral reassortants was prepared between equine rotaviruses H1 (G5),
      H2 (G3), and L338 (G13) and human rotavirus ST3 (G4). All contained the VP4
      cognate gene segment 4 from the equine parental virus and the VP7 cognate gene
      segment 9 from ST3. Using these viruses and antisera prepared to them, it was
      shown that each of the three equine viruses possessed a serologically distinct
      VP4 or P serotype with a > or = 16-fold difference in reciprocal cross
      neutralization titers. H1 VP4 was closely related to that of porcine virus OSU,
      i.e., P7. L338 gene 4 was sequenced, and the sequence and serological data
      indicated that it constituted a novel P serotype L338. P serotype H2 was
      predominant among our cell culture-adapted equine rotavirus strains, but showed
      some serological cross-reactivity.

PMID- 7514322
TI  - African swine fever virus structural protein p72 contains a conformational
      neutralizing epitope.
AB  - We have previously described a monoclonal antibody (mAb 135D4) to an unidentified
      70- to 72-kDa African swine fever virus (ASFV) protein that exhibited high levels
      of neutralizing activity against various virulent ASFV isolates. Here, we
      identify the reactive ASFV protein as the major virus structural protein p72. In
      vitro-translated products of the p72 protein gene were specifically
      immunoprecipitated by mAb 135D4. Immunoprecipitation of a nested set of truncated
      p72 in vitro translation products defined the region between amino acid residues
      400 and 404 as necessary for mAb 135D4 reactivity. Five partially overlapping
      peptides (15mers) covering residues 388-446 failed to react with mAb 135D4,
      suggesting the conformational dependence of the epitope. Supporting this
      interpretation, larger in vitro translation products representing residues 56
      282, 159-361, 360-508, and 507-646 also failed to react with mAb 135D4.
      Consistent with its involvement in virus neutralization, immunoelectromicroscopy,
      using a rabbit antiserum against mAb 135D4-purified p72, located the protein on
      the surface of unenveloped virus particles.

PMID- 7514323
TI  - [Immunophenotyping in chronic B-cell lymphatic leukemia].
AB  - The authors present the results of immunophenotyping analysis of cells from 67
      patients with the diagnosis of B-CLL from group of 393 adults examined by
      immunophenotyping because of a haematological malignity. Characteristic for B-CLL
      is the finding of surface molecules HLA DR, B lymphocytic superficial molecules
      and CD5. Aberrant membrane equipment of B-CLL cells is suggested by the rare
      absence of some pan B lymphocytic sign. Marked reduction of T lymphocyte ratios,
      their sub-populations and NK cells is associated with immunodeficiency
      manifestations which are common in patients with B-CLL.

PMID- 7514324
TI  - Evaluation of third-generation screening and confirmatory assays for HCV
      antibodies.
AB  - A third-generation (gen.) screening and immunoblot assay (Ortho EIA-3.0; Chiron
      RIBA-3 prototype), using antigens derived from the capsid and different
      nonstructural regions (NS3, NS4 and NS5) of the hepatitis C virus viral genome,
      were evaluated in comparison with the corresponding second-gen. assays (Ortho EIA
      2.0; revised Ortho EIA-2.5; Chiron RIBA-2). In 203 depository sera of blood
      donors, positive in EIA-2.0, specificity of the screening assays was improved as
      shown by an increase in positive predictive value for viral carrier state from
      0.23 (EIA-2.0) to 0.37 (EIA-2.5) and 0.52 (EIA-3.0). Comparing the confirmation
      patterns on RIBA-2 and RIBA-3, this amelioration was mainly due to the specific
      elimination of false-positive c22-3 and c100-3 reactions. Antibody response to
      the newly added NS5 antigen was not as prevalent as to the other antigens and had
      only a minor influence in sample allocation. In contrast, screening of 1,560
      volunteer blood donors and 47 hemodialysis patients revealed 3 additional
      positive sera, only reacting with the NS5 antigen. However none of these isolated
      NS5 reactions could be confirmed on synthetic peptides [INNO-LIA: NS5(p)] and
      none was PCR positive. A documented seroconversion, detected earlier with EIA
      3.0, was related to a better immunological response to the NS3 antigen and not to
      the additional NS5. From this pilot study third-gen. assays appeared extremely
      useful in the reevaluation of HCV-seropositive depository sera. However the
      additional value of the NS5 antigen in blood donor screening is still
      hypothetical and remains to be established in larger screening studies.

PMID- 7514326
TI  - Should the c100 antigen be removed from HCV antibody assays?

PMID- 7514331
TI  - Histochemical characteristics of the egg membranes of Portunus pelagicus (L.).
AB  - Incubated eggs of berried female crab Portunus pelagicus are hanged to the
      pleopodal setae by an attaching membrane. Each egg is protected by inner chorion
      and middle chitinous membrane. The middle chitinous and the outer attaching
      membranes form together a distinct case surrounding each egg. This case resists
      acids and alkalies and appears impermeable to water, salts and dye substances.
      The histochemical results provide evidence as to the origin of the chorion and
      suggest its function. The chitinous membrane is tanned, calcified and contains
      chitin. The attaching membrane is of lipoid nature and appears to be rich in
      polyphenols and phenolase enzyme suggesting the presence of phenolic tanning. The
      histochemical results confirm the cuticular origin and nature of the egg case.
      The tegumental glands of the pleopods are involved in the formation of the outer
      attaching membrane and/or at least the phenolase enzyme necessary for phenolic
      tanning. Larval release is a result of molting if the egg case is considered as a
      part of the outer cuticular exoskeleton of Portunus.

PMID- 7514327
TI  - Anti-GOR without anti-HCV core is not associated with hepatitis C viremia.

PMID- 7514325
TI  - Significance of HCV RIBA-2 indeterminate results in high-risk individuals:
      assessment by a new third-generation RIBA assay and PCR.

PMID- 7514329
TI  - [A method of fluorescent immunoenzyme analysis in the complex evaluation of viral
      and rickettsial vaccines].
AB  - With the use of the unified indirect solid-phase fluorescent enzyme immunoassay
      the combined evaluation of the antigenic and immunogenic properties of
      experimental whole-virion inactivated virus vaccines against Venezuelan and
      eastern equine encephalomyelitides, as well as of dried chemical typhus vaccine,
      has been made; their safety was determined indirectly by the content of
      ovalbumin. The protective role of antibodies evaluated by the solid-phase
      fluorescent enzyme immunoassay in typhus immunity has been shown.

PMID- 7514330
TI  - L-selectins revealed by immobilized analogue molecules on human peripheral blood
      lymphocytes.
AB  - The lymphocyte-endothelial interaction is initiated by selection type adhesion
      molecules on the surface of the lymphocytes (L-selectins) and by their
      carbohydrate ligands (addressins) in the glycocalyx of the endothelial cells.
      Under experimental conditions they can be substituted by analogue sugars, such as
      polyphosphonomonoester core polysaccharide and fucoidin. In this study, the
      expression of phosphomannosyl and fucoidin receptors is demonstrated on
      lymphocytes from human peripheral blood by polyacrylamide immobilized analogues.
      Based on adhesion and sugar inhibitory experiments, authors suggest that lineage
      and probably species specific differences exist in the expression and activity of
      the selectins responsible for binding of the two analogue molecules.

PMID- 7514328
TI  - [The identification of the antigenic determinants of Mycobacterium leprae passed
      through laboratory animals by using monoclonal antibodies].
AB  - The antigenic preparations of M. leprae isolated from the biopsy leproma material
      of leprosy patients, M. leprae obtained by passage through laboratory animals
      (armadillos, rats) and M. lepraemurium have been identified by indirect solid
      phase enzyme immunoassay. Experiments made with the use of the set of monoclonal
      antibodies (McAb) to different M. leprae antigenic determinants, supplied by the
      WHO Bank of Monoclonal Antibodies (IMMLEP), have demonstrated the presence of
      common antigenic determinants in 65-kD protein of M. leprae obtained by passage
      through armadillos and rats and M. lepraemurium, as well as in 12-kD protein of
      M. leprae isolated from armadillos and rats and M. leprae isolated from the
      biotic material of human lepromas. The passage of M. leprae through experimental
      animals leads to the appearance of a new antigenic determinant in their
      structure, which is recognized by McAb 111E4.

PMID- 7514333
TI  - Immunological studies of type I IGF receptors and insulin receptors:
      characterisation of hybrid and atypical receptor subtypes.

PMID- 7514332
TI  - Signal transducing mechanisms in interferon action (a brief review).
AB  - Experimental results suggest that protein kinase C (PK-C) may play a substantial
      role in the action of IFNs, but the precise biochemical pathway remains unknown.
      Recent evidences reveal the complexity of the mechanism of IFN-action and show
      that the IFN-alpha, -beta and -gamma induced pathways are overlapping. We briefly
      discuss what is known in this field and suggest a way in which the contrasting
      views might be reconciled.

PMID- 7514334
TI  - Multihormonal regulation of IGFBP-1 promoter activity.

PMID- 7514336
TI  - Rapid regulation of insulin-like growth factor binding protein-1 transcription by
      insulin in vivo and in vitro.

PMID- 7514335
TI  - Insulin-like growth factor binding protein-1: identification, purification, and
      regulation in fetal and adult life.
AB  - Circulating IGF bioactivity is reduced under a variety of conditions where
      anabolism is impaired. Serum IGF binding activity is increased in acutely
      diabetic animals and is regulated according to insulin status. Alterations in
      serum IGF binding activity reflects, at least in part, changes in circulating
      levels of IGFBP-1, suggesting that IGFBP-1 is an important modulator of IGF
      availability in post-natal life. Serum IGF binding activity and levels of IGFBP-1
      also are high in the hypoinsulinemic SGA fetal rat and levels of IGFBP-1
      correlate with fetal liver and body weight, indicating that IGFBP-1 contributes
      to the regulation of somatic growth in utero. Hepatic expression of IGFBP-1 is
      regulated at the level of gene transcription by insulin in a dominant negative
      fashion, while glucocorticoids and cAMP analogues exert positive effects on
      hepatocellular IGFBP-1 mRNA. Glucocorticoids exert important effects on
      circulating levels and hepatic expression of IGFBP-1 in vivo under conditions
      where insulin levels are low. Regulation of hepatic production of IGFBP-1 may
      provide a mechanism by which insulin and counter-regulatory factors may modulate
      the availability of IGFs and the biological effects of IGFs in both fetal and
      adult life.

PMID- 7514337
TI  - IGF binding protein-3 and the acid-labile subunit: formation of the ternary
      complex in vitro and in vivo.

PMID- 7514339
TI  - Cellular actions of insulin-like growth factor binding protein-3.

PMID- 7514338
TI  - Role of post translational modifications in modifying the biologic activity of
      insulin like growth factor binding proteins.

PMID- 7514340
TI  - Gene expression of the IGF binding proteins during post-implantation
      embryogenesis of the mouse; comparison with the expression of IGF-I and -II and
      their receptors in rodent and human.
AB  - The IGF binding proteins (IGFBPs) comprise at least six distinct species which
      may modulate the action of IGFs. IGFs are important regulators of fetal growth
      and differentiation. We have studied the mRNA expression of the six IGFBPs during
      post-implantation embryogenesis (day 11-18) by in situ hybridization techniques.
      Expression of IGFBP-1 was detected in mouse conceptuses after day 12 of gestation
      and seemed restricted to the liver. Transcripts for IGFBP-2, -4 and -5 were
      detected in various tissues and were found in all stages tested. In contrast,
      expression of IGFBP-3 and -6 could be detected only weakly in late gestational
      embryos. Comparison of the expression pattern of IGFBP-2, -4 and -5, which were
      found widely distributed in mouse conceptuses, revealed that IGFBP-2 was
      expressed mainly in the ectodermal layer and also in the mesoderm derived part of
      the tongue (day 13.5). Transcripts for IGFBP-4 however, only were detected in the
      mesoderm derived tissues, whereas expression of IGFBP-5 was restricted to the
      ectodermal layer. A similar distribution pattern was observed in the lung. In
      general, expression of IGFBP-2 and -5 was detected in the same cells, whereas
      IGFBP-4 and -5 were expressed mainly in different cell types. In rodents as in
      the human there is widespread expression of the genes coding IGFs, the IGFBPs and
      the receptors during pre- and postimplantation embryogenesis. These data support
      the assumption that the IGFs play an important role during embryogenesis.

PMID- 7514341
TI  - Hormonal regulation of insulin-like growth factor binding protein-1 expression
      and the development of transgenic mouse models to study IGFBP-1 function.

PMID- 7514342
TI  - Limited proteolysis of insulin-like growth factor binding protein-3 (IGFBP-3): a
      physiological mechanism in the regulation of IGF bioavailability.

PMID- 7514343
TI  - Effects of insulin-like growth factor I (IGF-I) administrations on serum IGF
      binding proteins (IGFBPs) in patients with growth hormone deficiency.

PMID- 7514344
TI  - IGF-II in the pathogenesis of rhabdomyosarcoma: a prototype of IGFs involvement
      in human tumorigenesis.

PMID- 7514347
TI  - Insulin-like growth factor (IGF) binding protein-1 is an antigonadotropin:
      evidence that optimal follicle-stimulating hormone action in ovarian granulosa
      cells is contingent upon amplification by endogenously-derived IGFs.

PMID- 7514345
TI  - Analysis of the interaction of IGF-I analogs with the IGF-I receptor and IGF
      binding proteins.
AB  - Distinct domains of IGF-I are important for maintaining high affinity for the IGF
      I receptor and for the various species of IGFBPs. The analogs that selectively
      bind the receptor have proven useful in determining the relative importance of
      IGFBPs in the regulation of the biological activity of IGF-I. Analogs with poor
      affinity for the receptor have also been useful in order to demonstrate that a
      given activity of IGF-I is mediated by the type 1 IGF receptor. These studies
      confirm that the role of these various proteins in IGF-I action is complex, and
      may be cell or tissue-type specific.

PMID- 7514348
TI  - Insulin-like growth factor-I and insulin-like growth factor binding proteins in
      the Zucker fatty rat: a case for differential tissue regulation.

PMID- 7514349
TI  - Characterization of the IGF regulatory system in bone.

PMID- 7514350
TI  - Regulation of IGF activity in bone.

PMID- 7514346
TI  - Regulation of IGFBP-4 and -5 expression in rat granulosa cells.

PMID- 7514351
TI  - Synthesis and characterization of IGF-II analogs: applications in the evaluation
      of IGF receptor function and IGF-independent actions of IGFBPs.

PMID- 7514352
TI  - Towards identification of a binding site on insulin-like growth factor-II for IGF
      binding proteins.

PMID- 7514353
TI  - An operational model of the antigen-antibody interaction.
AB  - A description of the antigen-antibody interaction based on the mass action law is
      applied to the complex system of a heterogeneous antigen and a mixture of
      antibodies. A model of this system is constructed and mathematically described.
      It provides a tool for the simulation of immunoassays.

PMID- 7514357
TI  - CD34 immunohistochemistry of bone marrow biopsies: prognostic significance in
      primary myelodysplastic syndromes.
AB  - Bone marrow (BM) biopsies from 58 patients with primary myelodysplastic syndrome
      (MDS) were studied using QBEND10, a monoclonal antibody that recognizes the human
      progenitor CD34 antigen in routine aldehyde-fixed paraffin-embedded samples. FAB
      subtypes were RA (5 patients), RARS (9 patients), RAEB (20 patients), RAEBt (11
      patients), CMML (3 patients). In addition, 10 MDS patients whose BM biopsies
      revealed heavy reticulum fibrosis were included. Neither the percentage of CD34+
      cells nor the number of CD34+ aggregates (defined as clusters of 3 or more cells)
      correlated with the presence and morphology of abnormal localizations of immature
      precursors (ALIP). When all patients were considered, median survival was 69
      months in those with less, and 25 months in patients with more than 1% CD34+
      cells (P < 0.05). Median survival was 15 months in patients with CD34+ aggregates
      and 41 months in those without aggregates (P = 0.0017). When RAEB patients were
      considered median survival was 41 months in those with less than 1%, and 29
      months in those with more than 1% CD34+ cells; the 4-year survival chance was 45%
      in the former and 18.3% in the latter group. Therefore, CD34 positivity of more
      than 1% identifies a subset of RAEB patients with shorter life expectancy. In
      addition, leukemic transformation was observed in 11 of 35 patients (31%) with no
      CD34 aggregates, but in 14 of 23 patients (60%) with aggregates (P < 0.05). CD34
      immunostaining, which can be easily performed on routinely prepared BM biopsies,
      was found to be a powerful prognostic tool for predicting survival and outcome in
      MDS.

PMID- 7514354
TI  - Identification of seroreactive epitopes of human papillomavirus type 18 E7
      protein by synthetic peptides.
AB  - Nine everlapping peptides covering the entire sequence of early protein E7 of
      human papillomavirus type 18 (HPV-18) were synthesized and tested as antigens
      with pools of selected human sera in ELISA. Peptides denoted 18/E7-2, 18/E7-3,
      and 18/E7-5 (amino acid positions 11-33, 21-40, and 41-60, respectively) were
      reactive with pooled sera originating from HPV-18 DNA-positive cervical cancer
      patients but not with sera from HPV-16 DNA-positive cervical cancer patients or
      from condyloma acuminata patients. This suggested that the epitopes contained in
      these peptides were HPV-18 type-specific, relative to HPV types 16, 11, and 6. On
      the other hand, 18/E7-1 (aa 1-23) and 18/E7-6 (aa 51-70) peptides were cross
      reactive. The prevalence of antibodies reactive with 18/E7-2, 18/E7-3, and 18/E7
      5 peptides in cervical carcinoma patients was very low. Thus, the utilization of
      these peptides for monitoring HPV-18 infection seems to be rather limited.

PMID- 7514356
TI  - Enhancement of pain control with ketorolac tromethamine in patients with sickle
      cell vaso-occlusive crisis.
AB  - Twenty one patients with sickle cell disease admitted to the hospital with the
      pain of vaso-occlusive crisis (VOC) were treated by continuous IV infusion of
      ketorolac or normal saline for up to 5 days. All patients received supplemental
      IM injections of meperidine, 100 mg, as necessary, but not more frequently than
      every 3 hr. Over the 5 days the ketorolac treated patients (KT) required 33% less
      meperidine than did the placebo treated patients (PL), P = 0.04, and had
      significantly better pain relief as assessed by categorical, visual analog, and
      pain relief scales. By the end of 5 days infusions had been discontinued in six
      KT and one PL. The time to discontinuation of the infusion was significantly
      shorter in KT, (P = 0.009). The median duration of hospital stay from the start
      of treatment was 3.3 days for KT and 7.2 days for PL, P = 0.027. Adverse events
      were mainly related to the digestive system. This study showed that continuous
      infusion of ketorolac significantly reduced total meperidine requirement and that
      the analgesia produced by this combination was superior to that produced by
      meperidine alone. Further evaluation of this drug in the management of sickle
      cell VOC is warranted.

PMID- 7514355
TI  - Sequential peripheral blood progenitor cell transplantation after mobilization
      with salvage chemotherapy and G-CSF in patients with resistant lymphoma.
AB  - We enrolled 18 patients affected by refractory or relapsed lymphoma (HD, NHL) in
      a two-step protocol that included salvage chemotherapy with mitoxantrone,
      carboplatinum, methylprednisolone, and cytosine arabinoside (MiCMA) plus G-CSF (5
      micrograms/kg/day), peripheral blood progenitor cell (PBPC) collection, and
      subsequent transplantation after BUCY2 regimen. After MiCMA chemotherapy, four
      patients (22%) achieved complete response, eight patients (44%) obtained a
      partial response, and six showed progression of disease (PD). Fourteen out of 18
      patients (78%) were considered eligible for PBPC transplantation. Three patients
      with complete response refused PBPCT; they are currently in continuous complete
      remission (CCR) at 15, 13, and 15 months, respectively. One patient has been
      recently transplanted but is too early to be evaluated. Ten patients so far
      completed the study, eight of whom are currently alive in CR, with a median
      follow-up of 7.5 months (range 2-13). Hematologic reconstitution was very rapid
      with a median time to achieve WBC > 1 x 10(9)/L, PMN > 0.5 x 10(9)/L, platelets >
      50 x 10(9)/L and > 100 x 10(9)/L of 13 (range 9-15), 12 (range 9-14), 10 (range 0
      22), and 14 (range 5-49) days, respectively. Our protocol is highly effective as
      a salvage treatment, while permitting PBPC collection after G-CSF administration.
      Hemopoietic reconstitution after transplantation of PBPCs collected with this
      procedure is complete, rapid, and sustained.

PMID- 7514358
TI  - P-selectin and ICAM-1-dependent adherence reactions: role in the genesis of
      postischemic no-reflow.
AB  - The aim of this study was to determine whether immunoneutralization of P-selectin
      or intercellular adhesion molecule-1 (ICAM-1) (endothelial cell adhesion
      molecules involved in leukocyte rolling and firm adhesion, respectively) would
      attenuate the development of postischemic capillary no-reflow. Microvascular
      patency was assessed in vascularly isolated canine gracilis muscles by perfusion
      with contrast media (India ink) at the end of the experimental protocol.
      Computerized video imaging was used to quantitate the number of ink-containing
      microvessels (< 10 microns diam) per muscle fiber in histological samples
      obtained from isolated canine gracilis muscles subjected to 4.5 h of continuous
      perfusion (nonischemic control), 4 h of ischemia and 30 min of reperfusion (I-R),
      I-R + P-selectin monoclonal antibodies (MAbs) (MD6 or PB1.3), and I-R + ICAM-1
      MAbs (CL18/6C7 or R6.5). The efficacy of a P-selectin MAb (MD3) that binds to a
      nonfunctional epitope was also evaluated. I-R was associated with a marked
      reduction in the number of patent capillaries per fiber (3.1 +/- 0.2 vs. 1.1 +/-
      0.2 patent capillaries/fiber for control and I-R, respectively).
      Immunoneutralization with MAbs directed against functional epitopes on P-selectin
      (MD6 or PB1.3) significantly improved capillary perfusion (2.3 +/- 0.3 and 3.6 +/
      0.6 patent capillaries/fiber, respectively). On the other hand, MAb MD3, which
      binds to nonfunctional epitopes on P-selectin, failed to limit the development of
      postischemic no-reflow (1.0 +/- 0.2 patent capillaries/fiber).
      Immunoneutralization of ICAM-1 with CL18/6C7 and R6.5 increased the number of
      patent capillaries per fiber to 1.8 +/- 0.1 and 2.5 +/- 0.3, respectively. These
      data indicate that P-selectin and ICAM-1-dependent adherence reactions play an
      important role in the development of the no-reflow phenomenon in postischemic
      skeletal muscle.

PMID- 7514360
TI  - Modulation of autonomic responses in normal and denervated isolated canine atria
      by substance P.
AB  - The experiments were performed to determine whether the neuromodulatory effect of
      substance P (SP) could be demonstrated in the isolated atrium. Strips from the
      right (RA) and left atria (LA) of normal (control) and denervated canine hearts
      were placed in an isolated muscle bath, and isometric muscle tension was
      measured. Inotropic responses to direct muscarinic stimulation were obtained with
      1 x 10(-9) to 1 x 10(-8) M acetylcholine (ACh), and responses to stimulation of
      the intramyocardial intrinsic cardiac nerves (ICN) were produced with nicotine
      (Nic), 1.0-10 x 10(-6) M. The same drugs were tested in the presence of 1 x 10(
      6) M SP, which had no significant inotropic effects of its own. Responses to ACh
      were unaffected by SP. The primary negative inotropic response to Nic was greatly
      attenuated by SP in both control and denervated atria, whereas the secondary
      positive response in control atria was unaffected. This inhibition was very
      pronounced in LA but less so in the RA. We conclude that SP appears to modulate
      the responses of the ICN to nicotinic stimulation in a manner similar to that
      previously observed in intact animals. This mechanism may provide a means of
      direct modification of efferent cardiac responses by afferent nerves within the
      heart itself.

PMID- 7514361
TI  - Human uterine arterial relaxation induced by nitroxidergic nerve stimulation.
AB  - Uterine arterial strips obtained from humans responded to nicotine with a
      contraction, which was abolished by prazosin. In the arteries treated with the
      alpha 1-receptor antagonist and partially contracted with serotonin, nicotine
      produced a relaxation that was not influenced by treatment with atropine or
      timolol and endothelium denudation but was abolished by hexamethonium,
      oxyhemoglobin, and NG-nitro-L-arginine (L-NNA). The inhibitory effect of L-NNA
      was reversed by L- but not D-arginine. Relaxations induced by nitroglycerin and
      nitric oxide (NO) were not affected by L-NNA but were abolished by oxyhemoglobin.
      Transmural electrical stimulation relaxed the arterial strips treated with
      prazosin; this response was abolished by L-NNA and restored by L-arginine.
      Histochemical study with NO synthase antiserum demonstrated the presence of
      immunoreactive nerve fibers in the adventitia. It may be concluded that human
      uterine arteries are innervated by vasodilator nerves that liberate NO as a
      neurotransmitter after chemical or electrical stimulation. Predominant
      vasoconstriction due to nerve stimulation appears to be associated with
      activation of alpha 1-adrenoceptors by neurogenic norepinephrine.

PMID- 7514364
TI  - Evolution of marsupial and other vertebrate thyroxine-binding plasma proteins.
AB  - Binding of radioactive thyroxine to proteins in the plasma of vertebrates was
      studied by electrophoresis followed by autoradiography. Albumin was found to be a
      thyroxine carrier in the blood of all studied fish, amphibians, reptiles,
      monotremes, marsupials, eutherians (placental mammals), and birds. Thyroxine
      binding to transthyretin was detected in the blood of eutherians, diprotodont
      marsupials, and birds, but not in blood from fish, toads, reptiles, monotremes,
      and Australian polyprotodont marsupials. Globulins binding thyroxine were only
      observed in the plasma of some mammals. Apparently, albumin is the
      phylogenetically oldest thyroxine carrier in vertebrate blood. Transthyretin gene
      expression in the liver developed in parallel, and independently, in the
      evolutionary lineages leading to eutherians, to diprotodont marsupials, and to
      birds. In contrast, high transthyretin mRNA levels, strong synthesis, and
      secretion of transthyretin in choroid plexus from reptiles and birds indicate
      that transthyretin gene expression in the choroid plexus evolved much earlier
      than in the liver, probably at the stage of the stem reptiles. NH2-terminal
      sequence analysis suggests a change of transthyretin pre-mRNA splicing during
      evolution.

PMID- 7514365
TI  - Risperidone.

PMID- 7514366
TI  - Risperidone in the treatment of schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to investigate the safety and efficacy
      of risperidone in the treatment of schizophrenic patients and determine its
      optimal dose. METHOD: This double-blind study included 388 schizophrenic patients
      drawn from 20 sites in the United States. Patients were randomly assigned to 8
      weeks' treatment with placebo, one of four doses of risperidone (2, 6, 10, or 16
      mg), or 20 mg of haloperidol daily. RESULTS: Clinical improvement (20% reduction
      in total scores on the Positive and Negative Syndrome Scale for Schizophrenia) at
      the study end point was shown by 35% of the patients receiving 2 mg of
      risperidone, 57% receiving 6 mg, 40% receiving 10 mg, and 51% receiving 16 mg;
      and by 30% receiving haloperidol and 22% receiving placebo. Statistically
      significant differences in clinical improvement were found between 6 and 16 mg of
      risperidone versus placebo and versus haloperidol. Positive symptom scores were
      significantly lower after 6, 10, and 16 mg of risperidone and 20 mg of
      haloperidol than placebo; negative symptom scores, however, were reduced
      significantly, compared with placebo, only after 6 and 16 mg of risperidone. The
      incidence of extra-pyramidal side effects (measured by the Extrapyramidal Symptom
      Rating Scale) was significantly higher in patients treated with 16 mg of
      risperidone or 20 mg of haloperidol than placebo. The results indicate that the
      optimal daily dose of risperidone for most schizophrenic patients in this study
      was 6 mg; this dose was as effective as 16 mg, and the incidence of
      extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher
      than that in patients receiving placebo. CONCLUSIONS: Risperidone is a safe
      antipsychotic that is effective against both the positive and negative symptoms
      of schizophrenia.

PMID- 7514362
TI  - CO2 and cerebral circulation in newborn pigs: cyclic nucleotides and prostanoids
      in vascular regulation.
AB  - The role of cyclic nucleotides and prostanoids in cerebrovascular reactivity to
      increased carbon dioxide was investigated in anesthetized and artificially
      ventilated newborn pigs equipped with closed cranial windows. Pial arteriolar
      diameter was measured, and cortical periarachnoid cerebrospinal fluid (CSF) was
      collected from beneath the cranial window for determination of adenosine 3',5'
      cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), and
      prostanoids. Progressively increasing arterial PCO2 (PaCO2) from normocapnia (33
      +/- 1 mmHg) to hypercapnia (final PaCO2, 83 +/- 2 mmHg) resulted in dose
      dependent pial arteriolar dilation and concomitant increases in cAMP, cGMP, and 6
      ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in cortical CSF. N omega-methyl-L
      arginine, N omega-nitro-L-arginine, N omega-nitro-L-arginine methyl ester,
      methylene blue, and LY 83583 did not inhibit cerebral vasodilation or the
      increases in cortical cAMP/cGMP induced by hypercapnia. Indomethacin abolished
      the vasodilatory response to hypercapnia and attenuated the hypercapnia-induced
      increases in cAMP and cGMP. Prostacyclin analogues increased both cAMP and cGMP
      levels in cortical CSF and induced pial arteriolar dilation (iloprost >
      carbaprostacyclin). The present data suggest that in newborn pigs cyclic
      nucleotides are involved in cerebral vasodilation in response to hypercapnia via
      a prostanoid-dependent mechanism.

PMID- 7514363
TI  - Interleukin-1 beta and tumor necrosis factor-alpha synergistically induce NO
      synthase in rat vascular smooth muscle cells.
AB  - Cytokine-inducible nitric oxide (NO) production has been implicated in the
      pathogenesis of septic shock. The present study was designed to determine which
      cytokines induce expression of the NO synthase gene in rat aortic vascular smooth
      muscle cells (VSMC) in vitro and whether NO synthase gene expression is inducible
      in vivo. NO synthase mRNA appeared after 4-h exposure to interleukin-1 beta (IL-1
      beta), and levels continued to increase up to 24 h. Levels of NO synthase
      transcripts were greatest in VSMC treated with IL-1 beta (1 nM), lower in VSMC
      treated with Escherichia coli lipopolysaccharide (LPS; 100 micrograms/ml), and
      just detectable in VSMC treated with tumor necrosis factor-alpha (TNF-alpha; 1
      nM). IL-1 beta, TNF-alpha, and LPS each induced NO synthase activity, assessed by
      release of nitrite, conversion of L-arginine to L-citrulline, and increased
      levels of guanosine 3',5'-cyclic monophosphate, whereas IL-2, IL-6, and
      interferon-gamma were ineffective. IL-1 beta was more potent and effective than
      TNF-alpha; however, submaximal concentrations of TNF-alpha acted synergistically
      with IL-1 beta to induce NO synthase gene expression and activity. Inducible NO
      synthase mRNA was present in aorta from rats 6 h after treatment with LPS (5
      mg/kg), but not at 24 h. Synergistic activation of NO synthase gene expression in
      VSMC by IL-1 beta and TNF-alpha may contribute to hypotension in sepsis.

PMID- 7514359
TI  - Repeated endothelial removal augments intimal thickening and attenuates EDRF
      release.
AB  - To evaluate the significance of repeated denudation injury in progression of
      atherosclerosis, we performed a single and then a second balloon denudation on
      the rabbit carotid arteries. Morphological examinations and organ chamber
      experiments were performed, and the results were compared. On morphological
      examinations, reendothelialization was almost completed in 2 wk after
      redenudation, whereas it required 6 wk after a single denudation. Intimal
      thickening progressed after redenudation. Organ chamber experiments showed that
      contractile responses and endothelium-independent relaxation remained unchanged
      after redenudation. Endothelium-dependent relaxations to acetylcholine, ADP, and
      substance P decreased progressively by repeating denudation. These relaxation
      responses were inhibited by NG-nitro-L-arginine, hemoglobin, and methylene blue
      and were considered to be associated with the production and/or release of
      endothelium-derived relaxing factor-nitric oxide (EDRF-NO). The diffusion barrier
      mechanism for the decreased endothelium-dependent relaxations was ruled out using
      sandwich experiments. In conclusion, repeated endothelial denudation caused
      progression of intimal thickening and acceleration of endothelial regeneration,
      and repeated endothelial regeneration resulted in progressively less production
      and/or release of EDRF-NO.

PMID- 7514369
TI  - Utility of the prostate-specific antigen test.

PMID- 7514368
TI  - Prostate cancer screening.

PMID- 7514367
TI  - Differentiation of thyroid neoplasms by evaluating epithelial membrane antigen,
      Leu-7 antigen, epidermal growth factor receptor, and DNA content.
AB  - The expression of epithelial membrane antigen (EMA), Leu-7 antigen, epidermal
      growth factor receptor (EGFr), and deoxyribonucleic acid (DNA) content in 40
      thyroid nodules was investigated to identify those factors that might
      differentiate these lesions or correlate to their prognosis. There were 22
      carcinomas (16 papillary, 4 follicular, 1 anaplastic, 1 medullary) and 18 benign
      lesions prospectively obtained between 1989 and 1993. Patients' charts were
      reviewed to establish a database of known clinical prognostic indicators.
      Expression of EMA and Leu-7 was significant in malignant lesions when compared to
      benign lesions (P < 0.02 and P < 0.001). EMA was expressed significantly more
      frequently by follicular carcinomas than by follicular adenomas (P < 0.03). Leu-7
      antigen was expressed by all papillary carcinomas. Neither of these antigens
      showed any association with known clinical prognostic indicators. EGFr expression
      neither differentiated benign from malignant lesions nor correlated with
      prognostic factors. The presence of aneuploidy correlated with poor tumor
      differentiation (P < 0.02), but did not distinguish benign from malignant
      lesions. These results suggest that EMA expression may be useful for confirming
      malignancy in follicular neoplasms and that the expression of Leu-7 antigen can
      assist in distinguishing papillary carcinoma from benign lesions with
      pseudopapillae.

PMID- 7514370
TI  - Utility of the prostate-specific antigen test.

PMID- 7514371
TI  - Utility of the prostate-specific antigen test.

PMID- 7514372
TI  - Natural and synthetic CCK-58. Novel reagents for studying cholecystokinin
      physiology.
AB  - CCK-58 is a unique reagent for testing how segments of a peptide far removed from
      its active site can influence the expression of its biological activity.
      Indications of tertiary structure have come from studies with natural peptide
      purified from canine small intestine. These studies gave clear indications that
      tertiary structure affects CCK-58 bioactivity, but the small quantities of CCK-58
      available made it impossible to characterize completely how tertiary structure
      influenced bioactivity. Canine CCK-58 was synthesized manually using a solid
      support and was purified by reverse phase high pressure liquid chromatography
      (HPLC). Synthetic CCK-58 was characterized by isocratic reverse phase and
      gradient HPLC, amino acid analysis, mass spectral analysis, sequence analysis,
      and three bioassays. Synthetic and natural canine CCK-58 had the same elution
      profiles, amino acid composition, sequence, and mass. The two peptides were
      equipotent for the stimulation of pancreatic secretion. Natural canine CCK-58 was
      equipotent to CCK-8 for CCK "B" receptor binding, a further indication of the
      purity of the natural peptide. However, natural CCK-58 was more potent than CCK-8
      for CCK "A" receptor binding and less potent than CCK-8 for stimulation of
      pancreatic secretion. These data support the concept that CCK-58 has a stable
      tertiary structure. This structure does not affect its binding to CCK "B"
      receptors, enhances its binding to low affinity CCK "A" receptors, and decreases
      its activity expressed through binding to high affinity CCK "A" receptors. The
      concept of a stable tertiary structure is also supported by the fact that many
      antibodies directed towards the carboxyl terminus of cholecystokinin react better
      with CCK-8 than CCK-58. The availability of synthetic CCK-58 will allow analysis
      of its tertiary structure by physical and chemical methods as well as studies on
      how peptide tertiary structure can affect receptor binding, receptor activation,
      metabolism in blood, degradation in interstitial fluid, and inactivation at the
      receptor. Evaluating all of these systems will help investigators understand the
      regulation of cholecystokinin activity by its major endocrine form, CCK-58.

PMID- 7514373
TI  - Role of substance P in the regulation of ion transport by CCKA and CCKB receptors
      in mouse ileum.

PMID- 7514374
TI  - Cholecystokinin-induced pancreatic growth involves the high-affinity CCK receptor
      and concomitant activation of tyrosine kinase and phospholipase D.

PMID- 7514375
TI  - Second messenger activators regulate CCK mRNA in the human neuroepithelioma cell
      line SK-N-MCIXC.

PMID- 7514376
TI  - Cholecystokinin in the hormonal stimulation of amino acid uptake and pancreatic
      enzyme secretion.

PMID- 7514377
TI  - Biological evaluation of JMV180 cholecystokinin analogs.

PMID- 7514378
TI  - Intracellular pathways activated by erythropoietin.

PMID- 7514379
TI  - The expression and role of human erythropoietin receptor in erythroid and
      nonerythroid cells.

PMID- 7514380
TI  - Effects of G-CSF on erythropoiesis.

PMID- 7514382
TI  - Oesophageal carcinoma: laser palliation in 231 cases.
AB  - Two hundred and thirty-one patients of advanced oesophageal carcinoma were
      treated with Neodymium: Yttrium-Aluminium-Garnet (Nd:YAG) laser photocoagulation
      of tumour tissue to relieve distressing dysphagia. There were 155 males (67.1%)
      and 76 females (32.9%). The mean age was 59.6 years. Eighty-five percent (196
      cases) were above 50 years of age. Distribution of tumour by site was as follows:
      upper one-third--24 cases (10.4%), mid one-third--98 cases (42.4%) and lower one
      third--109 cases (47.1%). Squamous cell carcinomas accounted for 83.5% (193) of
      cases. Nearly two-thirds (144 cases, 62.3%) were more than 4 cm in length. Tumour
      deposits were found at more than one site in 11 cases (4.7%). Oesophageal lumen
      was restored in all cases but was poorly sustained in 19 cases (8.2%). Further
      sessions of laser therapy were required in all these cases. A mean of 2.7
      sessions of laser treatment was required to achieve adequate lumen. One hundred
      and eighty-nine patients (82%) had good relief of dysphagia to liquids and semi
      solids. Complications were seen in 20 cases (8.6%). There were no deaths related
      to the procedure. Mean survival was 5.5 months (1-14 months). Nd:YAG laser
      therapy offers effective palliation of dysphagia in carcinoma of the oesophagus
      with acceptable morbidity and no mortality.

PMID- 7514381
TI  - Relationship between endogenous erythropoietin levels, reticulocyte count, and
      reticulocyte RNA distribution. A study of anemic patients with and without renal
      failure.

PMID- 7514383
TI  - Towards a safe usage of lasers.
AB  - The increasing number of laser surgeons with different levels of education and
      training makes it important to develop good safety routines in order to minimise
      the risk of laser accidents. A specially educated and trained assistant, the key
      operator, is of great help in monitoring laser safety regulations in the
      operating room during surgery and supervising the function of the laser as well
      as executing changes in the laser power, laser mode, etc, at the surgeon's
      request. Provided that certain conditions, mainly concerning the concept of
      delegation, are taken into consideration, a cadre of key operators can be
      established also at small departments using lasers. From the authors' experience,
      the use of key operators is cost effective and beneficial to the surgeon, and
      that they have contributed significantly to laser safety at the department.

PMID- 7514384
TI  - Beta-thalassaemia mutations in west Malaysia: a new thalassaemia clinical score
      system.
AB  - The clinical severity of the mutations causing beta-thalassaemia in West Malaysia
      is presented. Thalassaemia clinical scores (Thal CS), a scoring system, has been
      formulated to predict clinical severity. It is the type of beta-thalassaemia
      mutation present that decides on the clinical phenotype. The most severe beta
      thalassaemia mutation is assigned a score of 4. A score of 8 indicates a severe
      thalassaemia phenotype. Alpha-thalassaemia, increased synthesis of Hb F, and
      glucose-6-phosphate deficiency may ameliorate the clinical condition at phenotype
      level, and the co-inheritance of hereditary ovalocytosis aggravates it.

PMID- 7514385
TI  - Current experience with antiviral therapy for acute herpes zoster.
AB  - Inhibition of varicella-zoster virus replication during acute herpes zoster
      would, theoretically, accelerate cutaneous healing and reduce the pain, both
      acute and chronic, associated with shingles. Early antiviral drugs were of
      limited efficacy, excessively toxic, or needed to be given parenterally, and were
      unsuitable for use in immunocompetent individuals. Acyclovir was a significant
      advance and remains the antiviral drug of choice for herpes zoster. There is
      ample evidence for its efficacy in acute illness, but its ability to influence
      post-herpetic neuralgia is controversial. This review also discusses the role of
      adjunctive therapy with steroids in acute shingles.

PMID- 7514386
TI  - Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine
      linked sugar chain of a soluble form of CD59 in human urine.
AB  - CD59 is an 18-kDa glycoprotein widely expressed on human cells. An important
      structural feature of CD59 is its attachment to the cell surface via a glycosyl
      phosphatidylinositol (GPI) anchor. CD59, like many GPI-anchored proteins, has
      been found in urine, serum, and other body fluids. The structures of the GPI
      anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine,
      U-CD59, were determined. Purified U-CD59 released 1 mol of inositol per mole of
      protein by nitrous acid deamination, which cleaved between glucosamine and
      inositol present commonly in the GPI anchor. This indicates that a GPI anchor,
      which ended with inositol, is linked at the carboxy terminus of U-CD59. The
      peptide containing an asparagine-linked sugar chain and the peptide containing a
      glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59.
      The asparagine-linked sugar chains and the glycan portion of the GPI anchor were
      isolated from these peptides following hydrazinolysis or deamination and
      dephosphorylation, respectively. Their structures were analyzed by sequential
      exoglycosidase digestion and methylation analyses. The structures of the
      asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2%
      of which are monosialylated. The backbone structure of the GPI anchor was similar
      to that of Try-panosoma brucei variant surface glycoprotein, but showed
      significant variations in its side-chain moieties. This is the first detailed
      structural analysis of the human GPI anchor and the first detailed analysis of
      the carboxyl-terminal structure of the soluble-form GPI-anchored protein. The
      results indicate that the backbone structure of the GPI anchor is conserved from
      parasites to human and that at least a part of the soluble-form GPI-anchored
      protein has the structure produced by the action of glycan-phosphatidylinositol
      specific phospholipase D.

PMID- 7514387
TI  - Properties of variant forms of human stem cell factor recombinantly expressed in
      Escherichia coli.
AB  - The gene for human stem cell factor (SCF) encodes a leader sequence followed by
      248 amino acids (Martin et al., 1990, Cell 63, 203). Of these 248 amino acids,
      the first 189 correspond to an extracellular domain and the remainder correspond
      to a hydrophobic transmembrane domain plus a cytoplasmic domain. A naturally
      occurring soluble form, released by proteolytic cleavage after amino acid 165,
      has been described. An alternatively spliced mRNA, lacking the codons for exon 6,
      has also been described. Since the amino acids encoded by exon 6 include the
      proteolytic cleavage site, the form expressed from the alternatively spliced mRNA
      tends to remain membrane-bound. In the present study, we have begun to explore
      structure/function relationships within the extracellular domain of SCF. Forms
      beginning at amino acid 1 (after the leader sequence) and ranging from 127 to 189
      at the C-terminus have been recombinantly expressed in Escherichia coli and
      purified. In addition, forms missing the amino acids encoded by exon 6, forms
      missing up to 10 amino acids from the N-terminus, and forms with disulfide bond
      alterations have been expressed and purified. The forms have been characterized
      structurally, as well as functionally, in quantitative cell proliferation and
      receptor-binding assays. The results indicate that amino acids 1-141 comprise a
      structural and functional core and allow conclusions about the necessity of each
      of the two disulfide bonds for structure and function.

PMID- 7514388
TI  - [Clinical usefulness of serum assay of EIA-CYFRA 21-1 in lung cancer].
AB  - Enzyme immunoassay CYFRA 21-1, a novel lung tumor marker presented in serum
      (upper limit of normal values: 3.5 ng/ml) was measured in 84 patients with lung
      cancer and 141 patients with benign respiratory diseases. The positive rate for
      CYFRA 21-1 in primary lung cancer was 70.3% and the false positive rate in
      respiratory diseases was 24.1%. In respect to the histological types of lung
      cancer, CYFRA 21-1 was elevated in 85.0% of squamous cell carcinoma and in 64.8%
      of other cell types of primary lung cancer. Elevated CYFRA 21-1 levels were found
      in 40% of Stage I-II, in 80.0% of Stage IIIA-B, and in 73.5% of Stage IV. The
      overall diagnostic efficiency was 53.4% for CYFRA 21-1 and 44.5% for CEA,
      respectively. Receiver operating characteristic (ROC) curve analysis suggested
      that CYFRA 21-1 test has an advantage over CEA. From the results of this study,
      CYFRA 21-1 was more efficient than CEA as primary diagnostic marker in lung
      cancer.

PMID- 7514389
TI  - [Autologous bone marrow transplantation following high-dose busulfan and
      etoposide for a patient with non-Hodgkin's lymphoma].
AB  - A 26-year-old man was admitted to our hospital with cervical tumor and facial
      edema on July 8, 1991. Examination of chest X-ray and chest CT showed a bulky
      tumor in the mediastinum and pleural effusion. A pathological diagnosis of non
      Hodgkin's lymphoma (diffuse large cell, immunoblastic type) was made by biopsy of
      the cervical lymph node. MACOP-B chemotherapy or other combination chemotherapy
      did not achieve complete remission. The man was given a preparative regimen
      consisting of busulfan at 16 mg/kg orally and 60 mg/kg of etoposide (Bu-Et); 30
      mg/kg of etoposide was administered by continuous intravenous infusion for 12
      hours on day-5 and day-4, before he received autologous bone marrow on February
      20. He was then given 300 micrograms of G-CSF was given to him to accelerate
      recovery of hematopoiesis from one day after BMT. The neutrophil count to
      500/microliters recovered on day 28, and residual tumors disappeared. Although
      moderate-grade stomatitis and nasal bleeding developed, these toxicities were
      controllable and no veno-occlusive disease resulted. Regimen-related toxicities
      of Bu-Et preparatory regimen have been generally considered to be severe, but
      continuous and separate administration of etoposide as reported in this case may
      be useful to reduce side effects of this preparatory regimen.

PMID- 7514390
TI  - Clinical and subclinical deficits at 8 years in a geographically defined cohort
      of low birthweight infants.
AB  - OBJECTIVE: To determine the prevalence of subclinical deficits in cognitive and
      motor function in low birthweight infants. DESIGN: Children of birth weight < or
      = 2000 g born to mothers resident in Merseyside in 1980-1 assessed using the
      Wechsler Intelligence Scale for Children (WISC), the Neale analysis of reading
      ability, and the Stott-Moyes-Henderson test of motor impairment (TOMI). Children
      attending normal schools assessed with controls matched for age, sex, and class
      in school. Children attending special schools were assessed unmatched. SUBJECTS:
      233 matched index case-control pairs attending normal primary schools and 46
      unmatched children attending special schools. SETTING: Primary and special
      schools. MAIN OUTCOME MEASURES: IQ score, reading age in months, and TOMI score.
      RESULTS: Index cases when compared with controls had a lower WISC score (mean IQ
      difference 8.8; 95% confidence interval (CI) 6.8 to 10.7), a lower reading age
      (mean difference 6.5 months; 95% CI 4.0 to 9.0), and poorer motor performance as
      shown by the TOMI score (mean difference 1.4; 95% CI 1.1 to 1.8). Of the children
      attending special schools, 23/46 (50%) had a WISC score < or = 50. CONCLUSIONS:
      Low birthweight children have significant subclinical deficits of cognitive and
      motor function and extra resources, especially in education, may be required to
      meet their needs.

PMID- 7514392
TI  - Pseudomonas cepacia.

PMID- 7514391
TI  - Neuropsychological and neurological outcome after relapse of lymphoblastic
      leukaemia.
AB  - Fourteen children who relapsed after initial remission of leukaemia were studied.
      Six received a second course of cranial radiotherapy, while the remaining eight
      children were given total body irradiation before bone marrow transplantation.
      The postirradiation somnolence syndrome was common after cranial radiotherapy.
      All children had mild/soft neurological signs, mostly of coordination. None had a
      major motor disability. All but the youngest child had cataracts; two children
      required an operation for these. All children were growth hormone deficient.
      Verbal IQ, attention, and concentration were selectively reduced (with respect to
      normative levels). The time between the two treatments, age at relapse, and
      higher doses of radiotherapy all correlated with cognitive outcome, with girls
      showing greater impairments than boys. Only two children were performing at age
      appropriate levels on measures of academic achievement. It is concluded that
      neurological and neuropsychological morbidity is significantly increased by the
      current treatments prescribed after the relapse of leukaemia.

PMID- 7514394
TI  - Safety of the blood supply. Surrogate testing and transmission of hepatitis C in
      patients after massive transfusion.
AB  - OBJECTIVE: To define a risk profile for post-transfusion hepatitis C in patients
      receiving massive transfusion. SUMMARY BACKGROUND DATA: Hepatitis C accounts for
      more than 90% of post-transfusion hepatitis. METHODS: Two-hundred twenty-one of
      8,765 consecutive trauma admissions to a Level I trauma center received more than
      20 units of erythrocytes. Sixty-nine survivors had positive viral serologic tests
      at least 1 year after transfusion. Surrogate testing for hepatitis C using
      alanine aminotransferase (ALT) levels and antibodies to hepatitis B core antigen
      (Core) began in October 1986 and January 1987, respectively. Donor blood for
      group 1 (pre-ALT/Core) was transfused before surrogate screening was introduced.
      Donor blood for group 2 (post-ALT/Core) was transfused after surrogate screening.
      RESULTS: Sixty-nine patients received blood products from 4,987 donors (mean,
      72.3 units of exposure). No patient tested positive for antibodies to hepatitis B
      surface antigen, human immunodeficiency virus, or human T-lymphotrophic virus
      type 1. However 23.2% tested positive for hepatitis C virus (HCV) as measured by
      a second-generation enzyme immunoassay (HCV 2.0) and a recombinant immunoblot
      assay (RIBA), and 21.7% tested positive by HCV 1.0. Antibodies to Core were found
      in 8.7% of patients. The risk for post-transfusion hepatitis C per unit of
      exposure is estimated to be 1.52% group 1 (pre-ALT/Core) and 0.239% for group 2
      (post-ALT/Core). CONCLUSIONS: The introduction of ALT/Core donor screening by a
      blood bank reduced the incidence of post-transfusion hepatitis C by 84%. The risk
      for post-transfusion hepatitis C depends on units of exposure, screening
      techniques, and prevalence of hepatitis C in the donor population. In our
      community, the risk for post-transfusion hepatitis C is less than 0.2% per unit
      of exposure. The population of massively transfused patients may serve as our
      effective resource for monitoring the safety of the blood supply.

PMID- 7514395
TI  - Stroke rehabilitation. 3. Rehabilitation evaluation and management.
AB  - This self-directed learning module highlights rehabilitation evaluation and
      management. Part of the chapter on stroke rehabilitation in the Self-Directed
      Medical Knowledge Program for practitioners and trainees in physical medicine and
      rehabilitation, this article contains sections on determining the level of
      rehabilitation needed after stroke, the common disabilities seen after a stroke
      and their evaluation and management, neurofacilitative approaches in stroke
      recovery, and the management of dysphagia and bladder and bowel dysfunction in
      the stroke patient.

PMID- 7514393
TI  - Altered angiotensin-II receptors in human hepatocellular and hepatic metastatic
      colon cancers.
AB  - OBJECTIVE: To characterize angiotensin-II receptor density and affinity in normal
      and cirrhotic livers and in hepatocellular and metastatic colorectal cancer.
      SUMMARY BACKGROUND DATA: Several studies have indicated a possible beneficial
      effect of angiotensin-II as a biologic response modifier in the treatment of
      hepatic or metastatic colon cancer. This is based on evidence that angiotensin-II
      will cause a selective increase in arterial vasoconstriction in normal liver
      compared with tumor. METHODS: Human hepatoma (5), metastatic colon (10), or
      cirrhotic (3) liver was obtained. Non-tumor-bearing regions served as normal
      liver. Angiotensin-II receptor binding was determined on membranes with 125I
      angiotensin-II and in situ studies were performed using the biotin-avidin
      detection system. RESULTS: Angiotensin-II receptor density was markedly down
      regulated in tumor compared with normal or cirrhotic liver. CONCLUSIONS: A loss
      of angiotensin-II receptors occurs on the neovasculature of hepatic tumors.

PMID- 7514396
TI  - Selection of patients for curative or palliative resection of esophageal cancer
      based on preoperative endoscopic ultrasonography.
AB  - OBJECTIVE: To assess the accuracy of pretreatment staging and the potential of
      using endosonographic findings to select patients for curative or palliative
      resection by comparing the preoperative endosonographic and computed tomographic
      (CT) findings with the histology of the surgical specimen. METHODS: Forty-two
      patients referred to our clinic with esophageal carcinoma underwent preoperative
      upper endoscopy with biopsy, endosonography, thoracic CT, and abdominal CT. Based
      on endoscopic ultrasonographic findings, patients with early-stage disease
      underwent en-bloc esophagogastrectomy, whereas those with advanced disease had a
      palliative transhiatal esophagectomy. Exceptions included patients with poor
      physiologic reserve who were treated by the transhiatal route. RESULTS: In eight
      patients, we were unable to pass the ultrasonographic endoscope. Seven of these
      eight had transmural tumors with nodal involvement on histologic study. Tumor
      length, based on endosonographic measurements, was correctly predicted in 34
      patients (85%). Extent of wall penetration was accurately predicted in 26 (76%)
      of the 34, and regional lymph node status was accurately predicted in 28 (82%) of
      the 34. Of the patients with sonographic wall penetration, 80% had histologic
      evidence of one or more positive nodes. Using the WNM staging system, endoscopic
      ultrasonography correctly staged the cancer in 68% of the patients. Three
      patients were treated with an inappropriate procedure. CONCLUSION: Endosonography
      is a reliable method for the preoperative staging and selection of patients for
      curative or palliative resection. Endosonographic wall penetration appears to be
      a critical factor in determining tumor spread.

PMID- 7514397
TI  - Overexpression and characterization of a recombinant form of rat calcineurin A.
AB  - Overexpression of rat recombinant calcineurin A catalytic subunit in E. coli was
      achieved using a system under control of the T7 promoter. The specific activity
      of the purified catalytic subunit was suppressed relative to native bovine
      calcineurin, with the extent of suppression depending upon the choice of
      substrate. Addition of calcineurin B subunit stimulated phosphatase activity to
      one third that of native calcineurin. The metal activators Mn2+ and Ni2+ as well
      as several anion inhibitors affected both native calcineurin and recombinant
      calcineurin A activity to the same extent. In addition, calcineurin B was
      required for inhibition by the immunosuppressive complex FK506-FK506-binding
      protein.

PMID- 7514398
TI  - Fluorescence postlabeling assay of RNA modification.
AB  - A new approach has been developed to assay RNA modification by combining
      enzymatic digestion of RNA to nucleoside monophosphate and fluorescence
      postlabeling. Nuclease P1 digestion of modified RNA affords both normal and
      modified nucleotides. The nucleotides are labeled in-situ with dansyl chloride
      via phosphoramidate derivatives with ethylenediamine following a procedure
      initially designed to synthesize fluorescence labeled deoxynucleotides. The
      postlabeled nucleotides are analyzed by HPLC using a fluorescence detector.
      Fluorescence postlabeling assay of 7-methylGmp in RNA exposed to dimethyl sulfate
      has validated the technique. In the presence of excess normal nucleotides, the
      limit of detection (LOD) lies between normal to modified nucleotide ratio of
      10(3) to 10(4). HPLC enrichment of the modified nucleotide from the normal
      nucleotides prior to labeling enhances the LOD by two orders of magnitude.

PMID- 7514399
TI  - Regulation of recombinant human granulocyte colony-stimulation factor production
      using herpes simplex virus 1 thymidine kinase gene.
AB  - For chronic neutropenic patients requiring long-term injection of recombinant
      human granulocyte colony-stimulating factor (rhG-CSF), a cellular transplantation
      system that can produce this cytokine stably and deliver it in a regulatory
      manner would be advantageous. In this study we aimed at developing a regulation
      system at cellular level using suicide vectors. We introduced the herpes simplex
      virus type 1 thymidine kinase (HSV-TK) gene into the rhG-CSF-producing NIH3T3
      cells and examined if ganciclovir (GCV) treatment of the cells could control the
      rhG-CSF production in vitro. The cells transfected with the HSV-TK gene showed a
      > 100-fold increase in sensitivity to GCV compared with the parent cells, and the
      median inhibitory dose of GCV to the transfected cells was less than 1.6 microM.
      The total amount of rhG-CSF production by these cells was strongly suppressed by
      GCV treatment. This regulatory method may be applicable to cytokine supplement
      gene therapy.

PMID- 7514400
TI  - Expression of prostate specific antigen on the surface of a filamentous phage.
AB  - We have constructed two phagemid vectors containing the gene coding for human
      Prostate Specific Antigen (PSA) translationally fused to a pelB signal sequence
      and minor coat protein III of phage fd leading to phage particles that carry PSA
      on their tips. Phages were characterized by Western blotting and by panning,
      using biotinylated monoclonal anti-PSA antibodies immobilized onto streptavidin
      coated microtitration wells. Binding of PSA-phages was 10(2)- to 5 x 10(3)-fold
      more effective than that of wild-type phages. Trypsin treatment of the phage
      abolished the specific binding. Competitive panning with different concentrations
      of added purified PSA demonstrated that binding was PSA specific. Finally,
      Western-blot analysis confirmed that full-length and shorter degradation products
      of the fusion between PSA and protein III were visible as probed with anti-PSA
      antibody.

PMID- 7514401
TI  - Human monocyte chemotactic proteins-2 and 3 (MCP-2 and MCP-3) attract human
      eosinophils and desensitize the chemotactic responses towards RANTES.
AB  - When synthetic monocyte chemotactic proteins (MCPs) were tested in a Boyden
      chamber assay system for eosinophil-chemotactic properties using human
      eosinophils, MCP-3 was found to be a potent and efficient (percentage input
      migrating cells) attractant with an ED50 near 2-3 nM. MCP-2 was less potent,
      exhibiting half maximal chemotaxis at 40 nM. Cross desensitization experiments of
      eosinophil-chemotaxis revealed that both MCP-3 and MCP-2 desensitized autologous
      responses. In addition, pretreatment of human eosinophils with natural RANTES
      desensitized chemotaxis towards MCP-3 as well as MCP-2, whereas pretreatment of
      eosinophils with MCP-3 desensitized, apart from responses to MCP-3, also
      responses against RANTES and MCP-2. These findings indicate that possibly both
      MCP-3 and MCP-2 elicit chemotactic responses via the RANTES-receptor on
      eosinophils.

PMID- 7514402
TI  - Characterization, expression and evolution of mouse beta 2-glycoprotein I
      (apolipoprotein H).
AB  - beta 2-glycoprotein I (beta 2I) is a 50kDa serum glycoprotein of ill defined
      function. Based upon its capacity to bind negatively charged phospholipids a
      number of possible inhibitory roles for beta 2I have been proposed. We have
      cloned and sequenced a full length mouse beta 2I cDNA clone and demonstrated that
      mouse beta 2I does not behave as an acute phase reactant following an
      experimentally induced inflammation. Phylogenetic analysis of the known mammalian
      beta 2I homologues has provided evidence that mouse beta 2I is the most divergent
      and is evolving at a faster rate than beta 2I in other species.

PMID- 7514403
TI  - Regulation of p42 and p44 MAP kinase isoforms in Rat-1 fibroblasts stably
      transfected with alpha 2C10 adrenoreceptors.
AB  - Stimulation of Rat-1 fibroblasts, stably transfected with alpha 2C10 receptors,
      with the specific alpha 2 agonist UK14304 led to the tyrosine phosphorylation and
      activation of the p42 and p44 isoforms of MAP kinase. Tyrosine phosphorylation of
      the MAP kinases was prevented by pertussis toxin. In unstimulated cells, there
      was constitutive tyrosine phosphorylation and activation of the p44 but not the
      p42 MAP kinase. This effect was not seen in non-transfected parental Rat-1
      fibroblasts.

PMID- 7514404
TI  - Insulin-stimulated tyrosine phosphorylation of protein kinase C alpha: evidence
      for direct interaction of the insulin receptor and protein kinase C in cells.
AB  - Insulin, in the presence of phorbol esters, was observed to stimulate the
      tyrosine phosphorylation of a major 80 kDa protein by immunoblotting with anti
      phosphotyrosine antibodies in Chinese hamster ovary cells overexpressing the
      insulin receptor and protein kinase C alpha. The protein was specifically
      immunoprecipitated by antibodies to protein kinase C and anti-phosphotyrosine
      antibodies were capable of immunoprecipitating protein kinase C enzymatic
      activity from these cells. When this tyrosine phosphorylated protein kinase C was
      treated with a tyrosine-specific phosphatase, a 35% decrease in its enzymatic
      activity was observed and this inhibition was blocked by inclusion of a tyrosine
      phosphatase inhibitor, vanadate, in the reaction mixture. These results indicate
      that under certain conditions insulin can stimulate the tyrosine phosphorylation
      of protein kinase C and this phosphorylation can affect its enzymatic activity.

PMID- 7514405
TI  - The role of cysteine-949 in the binding of transforming growth factor-beta 1 and
      transforming growth factor-beta 2 to alpha 2-macroglobulin.
AB  - The reaction of alpha 2-macroglobulin (alpha 2M) with proteinases or methylamine
      causes a major conformational change in alpha 2M and cleavage of the alpha 2M
      thiol ester bonds. The resulting free Cys residues (Cys-949) contain the only
      free thiol groups in alpha 2M. In this investigation, we explored the role of Cys
      949 in the binding of transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta
      2 to alpha 2M-methylamine. Modification of preformed alpha 2M-methylamine with
      iodoacetamide did not change the binding affinity of alpha 2M-methylamine for TGF
      beta 1 or TGF-beta 2; the apparent KD values were 82 nM and 10 nM, respectively.
      TGF-beta binding also remained unchanged when tested using an alpha 2M derivative
      prepared by simultaneous treatment of alpha 2M with methylamine and
      iodoacetamide. The slow thiol-disulfide exchange reaction that irreversibly
      stabilizes noncovalent growth factor-alpha 2M-methylamine complexes was
      completely inhibited by modification of Cys-949. These studies demonstrate that
      Cys-949 in alpha 2M is not essential for binding of TGF-beta 1 and TGF-beta 2
      noncovalently; however, this residue plays a critical role in the covalent
      stabilization step of the reaction mechanism.

PMID- 7514406
TI  - A unique antigenic determinant on collagen II closely associated with age related
      abnormal modification.
AB  - During aging, a variety of proteins undergo a non-enzymatic modification, such as
      oxidation, attachment of lipid peroxide, and glycation. In particular, the long
      lived extracellular matrix proteins in connective tissue may be common targets
      for this kind of modification which, in turn, is involved in the pathogenesis of
      age related diseases. In the present study, we demonstrate that the age related
      modification on collagen II generates (a) new epitope(s). Furthermore, we
      established an immunochemical assay which is specifically suited to monitor the
      extent of abnormal modification of collagen II.

PMID- 7514407
TI  - Chemosensitivity to the indoloquinone EO9 is correlated with DT-diaphorase
      activity and its gene expression.
AB  - EO9, a new bioreductive indoloquinone alkylating agent, requires activation by a
      two-electron reduction, which can be catalysed by the NAD(P)H:quinone
      oxidoreductase DT-diaphorase (DTD) (EC 1.6.99.2). Seven human and four murine
      tumor cell lines from different histological origins were evaluated for their DTD
      enzyme activity (evaluated using dichlorophenolindophenol and EO9 as substrates),
      DTD gene expression and chemosensitivity to EO9. In general the cell lines could
      be divided into two groups: leukemic cells which were relatively resistant to EO9
      (IC50 > or = 0.5 microM) and had no measurable DTD activity, and solid tumor
      cells, which were more sensitive to the drug (IC50 < 0.06 nM) and contained a
      high DTD activity (> 90 nmol/min/mg). The expression of the DTD gene was measured
      by semiquantitative PCR in the human cell lines and an excellent correlation
      between gene expression and enzyme activity was observed (r2 = 0.94). A higher
      DTD gene expression also correlated with higher chemosensitivity to EO9.
      Protection of chemosensitivity to EO9 by dicoumarol, a strong and specific
      inhibitor of DTD activity, was dependent on duration of exposure and
      concentration of dicoumarol. Inhibition was best observed by short exposure to
      dicoumarol and EO9 together, demonstrating that bioactivation of EO9 by DTD is
      essential. In conclusion, DTD activity and expression appear to predict
      sensitivity to EO9 in a variety of cell lines. Evaluation of activity or
      expression in patients' tumor samples might predict the response to EO9.

PMID- 7514408
TI  - Monoamine oxidase inhibitory effects of some 4-aminophenethylamine derivatives.
AB  - The in vitro and ex vivo monoamine oxidase (MAO) inhibitory effects of (+/-)4
      dimethylamino-alpha-methyl-phenethylamine (4-DMAA) and (+/-)4-methylamino-alpha
      methyl-phenethylamine (4-MAA) were reassessed, in comparison with the previously
      unstudied achiral parent compound, 4-dimethyl-aminophenethylamine (4-DMAPEA) and
      with a salt of 4-DMAA enriched in the levo isomer, ("-")-4-DMAA, using amiflamine
      [S-(+)-4-dimethylamino-alpha,2-dimethylphenethylamine] as positive control. The
      in vitro studies confirmed that 4-amino-alpha-methylphenethylamine derivatives
      are highly selective and reversible MAO-A inhibitors. Furthermore, ("-")-4DMAA
      was less active than the racemic mixture. The side chain-unsubstituted compound,
      4-DMAPEA, proved to be a nonselective and reversible MAO inhibitor. The ex vivo
      results, in which catecholamines, serotonin (5-HT) and their metabolites were
      measured in two brain regions after i.p. administration, confirmed the results
      obtained in vitro. These results are consistent with the suggestion that the 4
      amino group contributes to MAO inhibitory effects of alpha-methyl
      phenethylamines, and show that the presence and orientation of an alpha-methyl
      side chain substituent may be important when determining the potency and
      selectivity of these compounds. All compounds tested could be quantified by HPLC
      with electrochemical detection.

PMID- 7514409
TI  - Demonstration of ternary immunophilin-calcineurin complexes with the
      immunosuppressants cyclosporin and macrolide FK506.
AB  - The specificity of cyclosporin A (CsA) binding to the major intracellular
      receptor proteins, cyclophilin A and B, as well as the interaction of CsA with
      the phosphatase calcineurin were investigated. Binding of photoaffinity-labeled
      CsA (PL-CS), a photoaffinity probe of CsA, to recombinant human cyclophilin A and
      B is saturable and specific. Non-specific PL-CS binding to calcineurin is
      observed in the absence of cyclophilin and calmodulin. In the presence of
      cyclophilin, cyclosporin-calcineurin binding becomes specific. Ternary complexes
      containing an equimolar ratio of cyclophilin A or B, PL-CS and calcineurin are
      resolved using the chemical-crosslinking technique. The formation of these
      complexes is specific, calcium- but not calmodulin-dependent, and is only
      inhibitable by cyclosporins, which bind cyclophilin. The drug-immunophilin
      complex binds to the calcineurin A subunit. The proteolytic 43 kDa product of
      calcineurin A retains binding properties, suggesting that the C-terminal domains
      are not necessary for complex formation. A trimeric complex of FKBP-calcineurin
      is also formed with FK506, but not with rapamycin. As expected, these complexes
      are only competed with by homologous derivatives. Chemical crosslinking of
      photolabeled Jurkat T-cells strongly suggests that drug-calcineurin complexes are
      of biological relevance.

PMID- 7514410
TI  - Juvenile rheumatoid arthritis and the trimolecular complex (HLA, T cell receptor,
      and antigen). Differences from rheumatoid arthritis.

PMID- 7514411
TI  - B cell epitopes on nuclear autoantigens. What can they tell us?

PMID- 7514412
TI  - "Homozygosity" for the HLA-DR shared epitope contributes the highest risk for
      rheumatoid arthritis concordance in identical twins.
AB  - OBJECTIVE: To assess the contribution of HLA-DRB1 alleles in determining
      rheumatoid arthritis (RA) concordance in monozygotic twins. METHODS: Ninety-one
      monozygotic twins pairs in which at least 1 twin was affected were typed for HLA
      DRB1 using both serologic methods and polymerase chain reaction amplification
      with sequence-specific oligonucleotide hybridization. The role of DR4 and of the
      shared epitope in disease concordance was investigated. Relative risks (RR) with
      95% confidence intervals were determined. RESULTS: Increased concordance for RA
      was observed in both DR4 positive and shared epitope positive pairs (RR 3.4 and
      3.7, respectively). A 5-fold risk for RA concordance was seen in twins who were
      "homozygous" for the shared epitope, compared with those negative for the shared
      epitope. CONCLUSION: In the absence of the shared epitope, RA concordance in
      monozygotic twins is rare. In contrast, "homozygosity" for the shared epitope is
      the most important factor in determining RA concordance.

PMID- 7514413
TI  - Biochemistry and molecular biology of nitric oxide synthases.
AB  - Many mammalian cells synthesize nitric oxide (NO). Three different isoforms of NO
      synthase have been characterized, purified and cloned. The identity of the three
      isoforms at the amino acid level is 50-60%, in cases where the same isoform has
      been cloned from more than one species > 90% identity is found between species.
      Isozyme I is present in neuronal cells of the brain (where NO may mediate
      synaptic plasticity), in peripheral neurons (where NO acts as an atypical
      neurotransmitter relaxing vascular and non-vascular smooth muscle), in
      specialized epithelial cells, and in human skeletal muscle. Macrophages are
      induced with bacterial endotoxin and/or cytokines to express isozyme II. The high
      concentrations of NO produced by this inform have cytostatic effects on parasitic
      microorganisms and tumor cells. Very similar isozymes can be induced in various
      other cells such as smooth muscle cells, mesangial cells, endothelial cells,
      fibroblasts, hepatocytes, etc. The induced enzyme from rat hepatocytes has been
      cloned and shows 94% sequence identity with the mouse macrophage enzyme.
      Endothelial cells contain isoform III of NO synthase which seems to be unique for
      this cell type. Endothelium-derived NO is a physiologically significant
      vasodilator and inhibitor of platelet aggregation and adhesion. NO can also
      prevent leukocyte adhesion to the endothelium, and has also been shown to inhibit
      the proliferation of vascular smooth muscle cells. Thus at least three distinct
      isoforms of NO synthase are responsible for NO formation in mammals.

PMID- 7514414
TI  - Angiogenesis and endothelial cell function.
AB  - Endothelial cell growth is tightly regulated. During embryonic development
      endothelial cells rapidly proliferate thereby forming new blood vessels. Two
      different mechanisms contribute to the development of the vascular system:
      vasculogenesis, the development of blood vessels from in situ differentiating
      endothelial cells, and angiogenesis, the formation of capillaries from
      preexisting vessels. In the adult, endothelial cell turnover is very low but
      under a variety of pathological conditions such as tumor growth these cells
      quickly enter the cell cycle and divide. Vascular endothelial growth factor
      (VEGF) has been identified as a key regulatory paracrine growth factor for
      endothelial cells. Transient VEGF expression correlates with embryonic and tumor
      angiogenesis. On the other hand, constitutive expression of this factor in
      choroid plexus and kidney glomerular epithelium and its cognate receptors in
      adjacent fenestrated endothelium suggests a role for this ligand-receptor system
      in organotypic endothelial cell differentiation and capillary permeability of
      fenestrated endothelium.

PMID- 7514415
TI  - Inducible nitric oxide synthase in vascular smooth muscle.
AB  - Nitric oxide is a multifunctional regulator of the vascular system. In healthy
      blood vessels, nitric oxide is produced from L-arginine by the constitutive
      nitric oxide synthase in endothelial cells. In addition, vascular injury or
      inflammation cause the production of nitric oxide in most types of vascular
      cells, including vascular smooth muscle. This response to injury is due to the
      induction of a second type of nitric oxide synthase by cytokines such as
      interleukin-1 beta or tumor necrosis factor-alpha. Factors derived from blood
      (thrombin, plasmin) and from vascular cells (platelet-derived growth factor,
      transforming growth factor beta, insulin-like growth factor, epidermal growth
      factor and basic fibroblast growth factor), regulate the induction of nitric
      oxide synthesis in vascular smooth muscle cells. The endogenous production of
      nitric oxide by vascular smooth muscle at sites of injury may contribute to the
      local control of blood flow, vascular tone and blood fluidity. It may participate
      also to the remodeling of the injured blood vessel wall.

PMID- 7514416
TI  - Biodegradation of hexachlorocyclohexane isomers in soil and food environment.
AB  - Persistence of chlorinated hydrocarbon insecticides in the environment is well
      documented. One early introduced insecticide, hexachlorocyclohexane (HCH),
      popularly called BHC, was used in large quantities all over the world until
      recently. In India, even today, technical grade HCH is being used extensively.
      Theoretically, HCH has eight possible stereoisomers of which four (alpha, beta,
      gamma, and delta) predominate in the technical product. These isomers
      significantly differ between themselves with respect to their persistence and
      toxicity toward insects, birds, mammals, and other nontarget organisms. The
      relative proportion of HCH isomers is, therefore, crucial from a toxicology
      standpoint. This problem assumes importance in light of reports that the HCH
      isomers undergo interconversion in soil, water, animals, plants, insects, etc.
      The persistence of HCH can be attributed in part to the interconversion of HCH
      isomers, which also restrict their solubility. In the present review,
      biotransformation of HCH isomers, both under aerobic and anaerobic conditions,
      and their degradation pathways have been described. In addition, emphasis is
      given to the interconversion of HCH isomers, including interconversion
      mechanisms, as this area has not received adequate coverage in earlier reviews on
      HCH.

PMID- 7514417
TI  - Superparamagnetic beads: applications of solid-phase RT-PCR.
AB  - Solid-phase RT-PCR applications with Dynabeads Oligo (dT)25 allow the
      reproducible isolation and detection of low-abundance cDNA sequences from small
      cell and tissue samples. The reusable properties of the beads reduce reagent cost
      and provide large amounts of target cDNAs for downstream applications. Magnetic
      separation of pure target mRNA/cDNA sequences eliminates labor-intensive
      precipitation and extraction steps and provides mRNA/cDNA sequences absent of
      contamination.

PMID- 7514418
TI  - Immunomagnetic separation: a tool for microbiology.

PMID- 7514419
TI  - Synovial sarcoma. An immunohistochemical study of the epithelial component.
AB  - Twenty-five synovial sarcomas were studied with a battery of antibodies directed
      against keratin and epithelial membrane antigen (EMA). The keratin antibody MNF
      116 showed reactivity in 24 tumors. In addition, 22 tumors showed reactivity with
      the antibody Keratin Wide Spectrum, 20 with the antibody Keratin 56, 64, and 19
      with CAM 5.2. Seventeen tumors showed reactivity with EMA. The keratin and EMA
      reactivity was present in cells lining obvious cleft-like structures in biphasic
      tumors. In the spindle cell areas of both biphasic and monophasic fibrous tumors,
      we found clusters of a few reacting cells apparently located around small clefts.
      In the synovioblastic tumors, clusters of plump tumor cells reactive for both the
      keratins and EMA were present. In conclusion, we found that proper identification
      of epithelial differentiation in synovial sarcomas is facilitated by an
      immunohistochemical application of anti-epithelial antibodies. In most tumors,
      there was immunoreactivity for the same type of keratins as are normally
      identified in simple epithelia (the antibody CAM 5.2), but also for those found
      in stratified squamous epithelia (the antibody Keratin 56, 64). The results
      indicate that screening for epithelial features on paraffin sections in the
      various types of synovial sarcoma, even the poorly differentiated synovioblastic
      tumors, is improved if epithelial antibodies with a broad spectrum of reactivity
      are chosen.

PMID- 7514420
TI  - An efficient procedure for separate extraction of nuclear and cytoplasmic RNA
      from cell culture.

PMID- 7514422
TI  - Exposing contaminating phenol in nucleic acid preparations.

PMID- 7514421
TI  - Extraction of RNA from kiwi fruit tissues.

PMID- 7514424
TI  - A method to stain nuclei of Drosophila for confocal microscopy.
AB  - We report a method of staining nurse cell and follicle cell nuclei in Drosophila
      ovaries and nuclei in Drosophila embryos with the fluorescent dye propidium
      iodide. This technique was used to replace more commonly used 4', 6-diamidino-2
      phenylindole (DAPI) and Hoechst staining as a method of visualizing nuclear
      material in Drosophila. Propidium iodide has its maximum excitation at about 530
      nm and maximum fluorescence at 615 nm, and therefore it can be used as a
      fluorescent marker with confocal microscopes that do not have a UV excitation
      source. Another advantage of the described method is the convenience of
      simultaneous use of fluorescein as a second fluorophore in multicolor
      fluorescence. We show that the nuclear material in Drosophila ovaries and early
      embryos can be visualized with propidium iodide using both confocal and
      conventional fluorescence microscopy. We also test the combination of two
      fluorophores-propidium iodide for nuclear staining and fluorescein-labeled
      phalloidin for membrane-bound actin--in the same tissue.

PMID- 7514423
TI  - An improved T1/A ribonuclease protection assay.

PMID- 7514425
TI  - NMDA receptor channels: subunit-specific potentiation by reducing agents.
AB  - Sulfhydryl redox agents affect NMDA receptor activity. We investigated a putative
      redox site in four recombinant NMDA receptors. In 293 cells expressing NR1-NR2A
      channels dithiothreitol (DTT) rapidly potentiated L-glutamate-activated whole
      cell currents and decreased the time course of desensitization and deactivation.
      Part of the current potentiation (reversible component) and all kinetic changes
      reversed upon washout. The remaining potentiation (persistent component) was
      abolished by an oxidizing agent. The N-terminal 370 residues of NR2A mediate the
      reversible component in chimeric NR2 subunits. In cells expressing the NR1-NR2B, 
      NR2C, and -NR2D channels DTT elicited only a slowly developing, persistent
      potentiation and increased the deactivation time course. In these, but not in NR1
      NR2A, the DTT effect was rendered insensitive to reoxidation by alkylation.
      Reduced glutathione mimicked the DTT effects only in the NR1-NR2A receptor.
      Hence, molecularly distinct NMDA receptors differ profoundly in their responses
      to sulfhydryl redox agents.

PMID- 7514426
TI  - Cloning and localization of a conventional kinesin motor expressed exclusively in
      neurons.
AB  - Kinesin is a microtubule-based motor protein involved in organelle transport in
      neuronal and nonneuronal cells. Although a single kinesin motor has been thought
      to serve all cell types, we document here that neurons express a second
      conventional kinesin heavy chain (nKHC) that is 65% identical in amino acid
      sequence to the ubiquitously expressed kinesin heavy chain (uKHC). By preparing
      antibodies which distinguish between the two KHCs, we demonstrate that nKHC is a
      nucleotide-dependent microtubule-binding protein which partially cofractionates
      with membrane organelles. Immunolocalization experiments show that nKHC is
      distributed throughout the CNS but is highly enriched in subsets of neurons. In
      hippocampal neurons in culture, uKHC is distributed uniformly throughout the
      neuron, whereas nKHC is selectively concentrated in the cell body. These results
      demonstrate that mammalian neuronal tissue contains two conventional kinesin
      motors which may serve distinct functions in microtubule-based transport.

PMID- 7514427
TI  - Expression and coexpression of Trk receptors in subpopulations of adult primary
      sensory neurons projecting to identified peripheral targets.
AB  - To determine whether neurotrophins act on functionally distinct populations of
      adult sensory neurons, the distributions of mRNAs for TrkA and tyrosine kinase
      containing isoforms of TrkB and TrkC were determined in rat DRG neurons
      projecting to different peripheral targets. Whereas trkA was expressed by a very
      high percentage of visceral afferents, trkC was expressed frequently only in
      muscle afferents. Among cutaneous afferents, the size distributions for trkA- and
      trkC-positive cells showed little overlap. The percentages and size distributions
      of cells labeled for the trks argue strongly that almost all trkB-expressing
      cells must also express trkA or trkC. These results indicate that NGF and NT-3
      act on functionally distinct populations of adult sensory neurons and suggest
      that a sizeable number of small DRG neurons may not respond to neurotrophins via
      a known Trk in the adult rat.

PMID- 7514429
TI  - [Hepatic confluence tumors: results and quality of life according to the type of
      treatment].
AB  - We analyzed survival rate and quality of life according to the treatment modality
      in 52 patients with hilar tumors. Six of them underwent resection (11.5%); 4
      without hepatectomy, one left hepatectomy and one trisegmentectomy. The remaining
      46 patients were treated by: radiologic external-internal drainage (12),
      placement of percutaneous endoprostheses (14), surgical intubation (18), and
      cholangioanastomoses to segment III in 2. Prognostic factors (PITT and
      A.P.A.C.H.E. II), survival time and quality of life were analyzed. Survival and
      comfort index were significantly better (p < 0.001) in the resection group than
      in the palliation one. Among palliative procedures percutaneous endoprostheses
      and surgical intubation offered better quality of life (p < 0.001) than
      radiologic external-internal drainage. We conclude that resection improves
      survival and offers better quality of life than palliative procedures. Our
      results suggest that resection during laparotomy should be attempted in order to
      improve results in the treatment of hepatic confluence tumors.

PMID- 7514431
TI  - Education in palliative medicine: a review.
AB  - The development of the specialty of palliative medicine has produced variable
      activity in the field of medical education. This article reviews published papers
      (primarily from Europe but with reference to other countries) identifies the
      extent of activity, and notes the absence of evaluative work. Undergraduate and
      postgraduate activity is identified.

PMID- 7514430
TI  - The style of early clinical research reporting: what are we saying and how do we
      say it?
AB  - Phase II studies involving novel chemotherapy treatment are often first reported
      to the scientific community as a published abstract. This study was designed to
      determine how authors report their phase II abstract data and what types of
      conclusions are made. All 1992 phase II colorectal cancer abstracts from the 1992
      Proceedings of the American Society of Clinical Oncology were reviewed and
      analyzed for descriptive and quantitative data and conclusions. The response rate
      was the most commonly reported response statistic (28/29), with few studies
      reporting confidence intervals (4/29), median duration of response (5/29), or
      median survival (9/29). Toxicity data was quantitative in 21 trials and
      qualitative or absent in 8 trials. Conclusions about the toxicity data were
      ambiguous or absent in five trials. Conclusions about the response data included
      inappropriate use of terms, indirect or ambiguous language, or no conclusion.
      These results indicate that the reporting of phase II trials in abstract form is
      highly variable and plagued by problems that make data interpretation difficult.
      Recommendations for change are suggested.

PMID- 7514432
TI  - Neuropeptide-containing nerves in painful hypertrophic human scar tissue.
AB  - Specimens of hypertrophic scar tissue (n = 9), non-hypertrophic, flat scar tissue
      (n = 5) and control skin (n = 3) were obtained from eight adult females (aged 22
      56) and three adult males (aged 22-59). The specimens were studied histologically
      and immunohistochemically for vasoactive intestinal polypeptide, neuropeptide Y,
      calcitonin gene-related peptide, substance P, somatostatin, [Met]enkephalin,
      [Leu]enkephalin, and the enzyme dopamine beta-hydroxylase. The non-hypertrophic
      scar tissues were not dissimilar to the control tissue, but contained connective
      tissue in bundles with a greater number of collagen fibres. In the hypertrophic
      scar tissue of some patients, the dermis contained adipose tissue displaced
      upwards from the hypodermis. The connective tissue contained densely packed
      collagen fibres and fibroblasts; this region was devoid of hair follicles, sweat
      glands and blood vessels, although they were observed in the region of loosely
      packed connective tissue. The normal skin contained all the neuropeptides
      studied, except somatostatin-, and dopamine beta-hydroxylase-immunoreactive
      nerves, which were seen as single fibres or in nerve bundles, and were associated
      with blood vessels in the dermis. Neuropeptide Y-immunoreactive nerves were found
      in the arrector pili muscle, and neuropeptide Y-, vasoactive intestinal
      polypeptide-, calcitonin gene-related peptide-, [Met]enkephalin- and dopamine
      beta-hydroxylase-containing nerves were found within sweat glands. In patients
      with flat, non-hypertrophic scar tissue, neuropeptides and dopamine beta
      hydroxylase-containing nerves were absent. In patients with hypertrophic scars,
      the density of neuropeptide Y-, vasoactive intestinal polypeptide-, substance P-,
      calcitonin gene-related peptide- and dopamine beta-hydroxylase-immunoreactive
      nerves was greater in the dermis when compared with controls.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7514428
TI  - Embryonic neurons of the developing optic chiasm express L1 and CD44, cell
      surface molecules with opposing effects on retinal axon growth.
AB  - The first retinal ganglion cell axons arriving at the embryonic mouse ventral
      diencephalon encounter an inverted V-shaped neuronal array defining the midline
      and posterior boundaries of the future optic chiasm. These neurons express L1, an
      immunoglobulin superfamily molecule known to promote retinal axon outgrowth, and
      CD44, a cell surface molecule that we find inhibits embryonic retinal axon growth
      in vitro. Incoming retinal axons do not penetrate this L1/CD44 neuron array, but
      turn to establish the characteristic X-shaped optic chiasm along the anterior
      border of this array. These results suggest that L1/CD44 neurons may serve as an
      anatomical template for retinal axon pathways at the embryonic mouse ventral
      diencephalon.

PMID- 7514433
TI  - Weekly VAPEC-B chemotherapy for high grade non-Hodgkin's lymphoma: results of
      treatment in 184 patients.
AB  - BACKGROUND AND PATIENTS: A weekly schedule of chemotherapy (VAPEC-B) has been
      used to treat 184 consecutive patients with high grade non-Hodgkin's lymphoma
      (NHL). Median age for the group was 57 years (range 17-84) and 56% had stage IV
      disease. RESULTS: Following chemotherapy, 114 (62%) patients achieved CR or
      CR(u), 32 (17%) PR and 15 (8%) had not responded or progressed. Response to VAPEC
      B was highly stage dependent with 70% or more of patients with stages I-III
      achieving CR or CR(u) but only 50% of those with stage IV. Twenty-four (15%)
      patients died during treatment with VAPEC-B and in 13 cases death was due to
      sepsis. This complication occurred mainly in patients with stage IV disease aged
      60 years or older. After a median follow up period of 4.1 years, the actuarial 4
      year survival for 184 patients is 45%, an overall result heavily influenced by
      the poor outcome for 103 patients with stage IV disease (4 year survival of 28%).
      Patients with earlier stage disease fared correspondingly better (44% for stage
      III, 68% for stage II and 80% for stage I). CONCLUSIONS: VAPEC-B gives similar
      results to other chemotherapy regimens currently used in the treatment of high
      grade NHL and has the advantage of brevity. Caution is advised in patients over
      the age of 60 especially in the presence of stage IV disease and dose reduction
      or haemopoietic growth factor support should be considered in these
      circumstances.

PMID- 7514434
TI  - Dose-escalating induction chemotherapy supported by lenograstim preceding high
      dose consolidation chemotherapy for advanced breast cancer. Selection of the most
      acceptable regimen to induce maximal tumor response and investigation of the
      optimal time to collect peripheral blood progenitor cells for haematological
      rescue after high-dose consolidation chemotherapy.
AB  - BACKGROUND: In advanced breast cancer high-dose consolidation chemotherapy with
      haematological rescue has resulted in prolonged disease free and overall survival
      in a small percentage of patients. Maximal reduction of the tumor burden by
      intensive induction treatment preceding the high-dose chemotherapy may favor that
      outcome. The aims of this study were to find a rapid highly effective induction
      regimen with acceptable toxicity and to examine the optimal time for peripheral
      blood progenitor cell (PBPC) collection for haematological rescue. SUBJECTS AND
      METHODS: Twenty-four patients received 4 cycles of FAC chemotherapy (5-FU,
      adriamycin, cyclosphamide), each followed by 10 micrograms/kg/d of lenograstim
      (glycosylated rHuG-CSF) s.c. day 2 to 11. Chemotherapy was administered at 4 dose
      intensity levels with 6 patients including at each level (level 1:
      500(F)/50(A)/500(C) mg/m2/3wk, level 2: 500/50/500 mg/m2/2wk, level 3: 500/75/500
      mg/m2/2wk, m2/2wk, level 4: 500/75/1000 mg/m2/2wk d1 i.v.). In addition
      lenograstim (10 micrograms/kg/d s.c.) was administered for a period of 10 days
      before (period X) and after (period Y) chemotherapy. In 16 patients (4 at each
      dose intensity level) assessment of PBPC was performed during period X and Y as
      well as during cycle 1 and 4. A single apheresis to collect PBPC was planned
      during chemotherapy cycle 1. RESULTS: The best response was obtained at dose
      intensity level 3 (all 6 patients responded, 3 of them achieved CR) with
      acceptable toxicity. Peak circulating numbers of total CFC/ml blood were median
      5819 (period X), 4635 (cycle 1), 3807 (cycle 4) and 3519 (period Y) and occurred
      concurrently with peak circulating numbers of CD34+ cells. The and median 3.76 x
      10(6)/kg CD34+ cells. Three patients received high-dose consolidation
      chemotherapy with PBPC support. Recovery of ANC > 0.5 x 10(9)/l occurred on
      median day 11 and of platelets > 20 x 10(9)/l on median day 10. CONCLUSION: Dose
      intensity level 3 is the best usable induction regimen in this study. The optimal
      time for apheresis is either during lenograstim before chemotherapy treatment or
      during the first cycle of chemotherapy. Rapid haematological recovery was
      obtained by reinfusion of PBPC as sole source of support in the patients
      receiving high-dose consolidation chemotherapy.

PMID- 7514435
TI  - Ovarian and extragonadal malignant germ-cell tumors in females: a single
      institution experience with 43 patients.
AB  - From 1978 to 1992, 276 patients (pts) with MGCT were treated in our institution.
      Forty-three of the pts were female (15.5%). Median age at diagnosis was 20 years
      (newborn-70). Histology was dysgerminoma (D) in 14 pts (including 2 anaplastic
      D), endodermal sinus tumor (EST) in 9 pts, immature teratoma in 10 pts and mixed
      tumors in 10 pts. Primary locations were as follows: ovary (O) 33 pts and
      extragonadal (EG) 10 pts (pineal in 4 cases, mediastinum in 3, sacrum in 2 and
      pharynx in 1). Stage: I in 20 (16 O, 4 EG), II in 7 (5 O, 2 EG), III in 12 (10 O,
      2 EG) and IV in 4 (2 O, 2 EG). Serum AFP was elevated in 20/22 non-dysgerminoma
      pts, HCG in only 5 pts and LDH in 15/36 pts. TREATMENT RESULTS: Ovarian tumors:
      all but one pt (biopsy only) underwent surgery: unilateral oophorectomy was
      performed in 15 pts and bilateral oophorectomy (+/- hysterectomy, +/- others) in
      17 pts. Fourteen pts were rendered disease-free, 8 pts had residual tumor (RT) <
      2 cm and 11 RT > 2 cm. Chemotherapy (PVB or BEP) was given to 28 pts,
      radiotherapy to 2 pts and no additional treatment to 3. Finally, 30 pts achieved
      complete response (CR) and none have relapsed at a median follow-up of 43 months.
      EG tumors: None of the pts underwent radical surgery. Radiotherapy was applied to
      4 pineal tumors and BEP or PVB were given to all 10 pts. To date 6 pts are
      disease-free, 1 is alive with mature teratoma, 2 are alive with disease and 1
      died of toxic effects. The projected overall survival of the series as a whole is
      89% at 10 years, and it is significantly higher for pts without EST (p < 0.02)
      and for pts with AFP < 1000 (P < 0.01) and age < 22 years at diagnosis (p <
      0.01). The projected event-free survival at 10 years is 80.4% (87.7% for ovarian
      tumors vs. 54% for extragonadal, p = 0.05). No events were recorded after 28
      months. CONCLUSIONS: The present results reflect the dramatic effectiveness of
      cisplatin-based chemotherapy for ovarian MGCT and confirm that unilateral
      oophorectomy can preserve fertility without compromising cure. Age > 22 years,
      histology (EST) and serum AFP > 1000 ng/ml are possible prognostic factors
      (univariate analysis) to be tested in an independent body of data on cisplatin
      treated patients.

PMID- 7514436
TI  - Growth inhibition of follicular small-cleaved-cell lymphoma cells in short-term
      culture by interleukin-3.
AB  - BACKGROUND: The role of interleukin-3 (IL-3) in stimulating the growth of early
      myeloid progenitor cells is very well established. Therefore, IL-3 has been
      incorporated into many post-bone-marrow transplantation and intensive
      chemotherapy programs for the treatment of solid tumors and hematologic
      malignancies, including lymphomas. However, the effect of IL-3 on normal and
      malignant lymphocytes has not been well studied. PURPOSE: The purpose of this
      study was to evaluate the in vitro effect of IL-3 on the growth of follicular
      small-cleaved-cell lymphoma (FSCCL). MATERIALS AND METHODS: IL-3 receptor
      expression on the surface of CD19+ cells was determined by two-color flow
      cytometry measuring the receptor-binding of biotinylated IL-3 to CD19+ B-cells.
      Seven cases of FSCCL were compared to six normal controls. Cell proliferation was
      evaluated by [3H]thymidine incorporation into cells grown in suspension cultures.
      RESULTS: All seven cases of FSCCL expressed the IL-3 receptor on the surface of
      CD19+ cells, whereas all six cases of CD19+ cells isolated from the peripheral
      blood of normal donors did not express IL-3 receptors. IL-3 had antiproliferative
      activity against FSCCL as manifested by a decrease in [3H]thymidine incorporation
      and a decrease in the total number of cells after 72 hours of culture.
      CONCLUSION: IL-3 inhibits the growth of FSCCL cells in vitro. Clinical trials to
      evaluate the in vivo effect of IL-3 in patients with FSCCL are warranted.

PMID- 7514437
TI  - 5-Aza-2'-deoxycytidine induces growth inhibition and upregulation of epidermal
      growth factor receptor on human epithelial cancer cells.
AB  - BACKGROUND: The epidermal growth factor (EGF-R) receptor is an important growth
      regulator of epithelial cancer cells, and is presently considered a tumor
      associated antigen (TAA) which is overexpressed by several human cancers and
      barely detectable in most normal tissues. Since TAA density at the tumor cell
      surface is a critical factor regulating the efficiency of immunotargeting
      procedures, a therapeutic advantage may derive from the pharmacologic enhancement
      of membrane expression of such antigens on tumor cells. MATERIALS AND METHODS:
      Utilizing a panel of different human cancer cell lines of epithelial derivation,
      we have investigated in the in vitro effects of 5-aza-2'-deoxycytidine (5azaCdR),
      an antineoplastic agent able to induce gene activation and phenotypic modulation,
      on the surface expression of EGF-R by tumor cells. RESULTS: 5azaCdR (10-1000 nM)
      induced growth inhibition, in the absence of acute cell kill, on KB (human
      oropharyngeal carcinoma), LoVo and the drug-resistant clone LoVo-DX (colon
      carcinoma) and A549 (lung adenocarcinoma) cell lines, along with a significant
      enhancement of EGF-R expression at the tumor cell surface. A single 24 h pulse of
      5azaCdR, followed by 96 h of culture in drug-free medium, induced 50% growth
      inhibition on KB cells at a concentration (IC50) of 500 nM, on A549 (IC50 = 490
      nM), LoVo (IC50 = 400 nM) and LoVo-DX (IC50 = 100 nM) cell lines. Under these
      conditions the specific binding of 125I-EGF was significantly upregulated at the
      surface of growth-inhibited cancer cells. Scatchard analysis of EGF-binding data
      revealed no changes in the Kd of EGF-R for its ligand in 5azaCdR-treated tumor
      cells and demonstrated a significant increase in the number of both the high- and
      low-affinity EGF-binding sites on KB cells, while only one class of EGF-binding
      site was detectable on A549, LoVo and LoVo-DX tumor cell lines before and after
      exposure to 5azaCdR. The EGF-R upregulation induced by 5azaCdR was paralleled by
      the increased binding of the anti-EGF-R monoclonal antibody (MAb) 108.1 on the
      surface of cancer cells. Finally, the rate of endocytosis of the anti-EGF-R MAb
      by KB cells was not modified by drug treatment, indicating that exposure to
      5azaCdR does not hamper MAb internalization by the tumor cells. This latter
      represents an essential process for the cytotoxic effects of immunoconjugate
      drugs or toxins. CONCLUSIONS: We suggest a role for 5azaCdR in enhancing the
      efficacy of therapeutic approaches involving the use of anti-EGF-R
      immunoconjugated for the imaging and the treatment of human epithelial
      neoplasias.

PMID- 7514438
TI  - Tumour-induced hypoglycaemia: a case report.

PMID- 7514439
TI  - 2Chlorodeoxyadenosine therapy of patients with Waldenstrom macroglobulinemia
      previously treated with fludarabine.
AB  - BACKGROUND: Fludarabine monophosphate and 2Chlorodeoxyadenosine are nucleoside
      analogues with activity against Waldenstrom macroglobulinemia. However, it is not
      clear whether prior exposure to one analogue precludes response to the other
      compound. PATIENTS AND METHODS: Fourteen patients with Waldenstrom's
      macroglobulinemia and prior exposure to fludarabine were treated with two courses
      of 2chlorodeoxyadenosine. RESULTS: Three out of four patients that had previously
      responded to fludarabine and were relapsing from unmaintained remission, achieved
      a partial response with 2chlorodeoxyadenosine therapy. However, only one out of
      10 patients with disease resistant to fludarabine responded to
      2chlorodeoxyadenosine. CONCLUSIONS: 2chlorodeoxyadenosine may be effective in
      patients with Waldenstrom macroglobulinemia sensitive to fludarabine. However,
      this compound has limited activity for patients with disease resistant to
      fludarabine.

PMID- 7514440
TI  - Immunofluorescence analysis of B-1 cell ontogeny in the mouse.
AB  - In order to further understand the developmental aspects of B-1 cells, we
      characterized the ontogeny of this B cell population in the spleen and peritoneal
      cavity of BALB/c mice. Although there are B-1 cells in the spleen within the
      first 1-3 weeks after birth, they do not at any stage represent the majority of
      splenic B cells. Splenic B-1 cells reach peak levels at approximately 9 days
      after birth. The mesenteric lining that covers the small intestine of 7-day-old
      mice contains a population of IgM+ B cells, while at the same age, there are few
      lymphoid cells in the peritoneal cavity. Between 7 and 8 days after birth there
      is an influx of B cells into the peritoneal cavity. At 8 days, the first
      detectable peritoneal B cells appear to be of the B-1 type based on expression of
      IL-5 receptor and CD5. However, these peritoneal B-1 cells do not express Mac-1.
      This antigen is not expressed by the majority of peritoneal B-1 cells until 3
      weeks. This study indicates that the majority of early splenic B cells are not B
      1 cells and it suggests that the mesenteric tissues surrounding the gut contain B
      lymphocytes which traffic into the peritoneal cavity where they then reside.

PMID- 7514441
TI  - Stromal cell independent growth of bipotent B cell--macrophage precursors from
      murine fetal liver.
AB  - We have established stromal cell independent culture conditions under which
      single murine hematopoietic progenitor cells give rise to B lymphocytes and
      macrophages. IL-11, mast cell growth factor, and IL-7 are sufficient for the
      growth of B lineage cells from AA4.1+B220-Mac-1-Ly6A+ fetal liver cells isolated
      at day 12 of gestation. These conditions are also sufficient for commitment to
      myeloid differentiation, although CSF-1 is required for substantial growth of
      macrophages. The progenitors responding under these culture conditions: (i)
      require 8 days in culture before they become competent to respond to B cell
      mitogens in the presence of stromal cells and (ii) undergo a minimum of three
      cell divisions prior to Ig heavy chain allotype restriction. The findings suggest
      that the stromal cell dependency of immature hematopoietic cells may reflect a
      requirement for stromal cell derived growth factors. Further, this provides an in
      vitro system in which commitment and differentiation can be studied in single
      cells.

PMID- 7514442
TI  - Isolation of nitric oxide synthase from human platelets.
AB  - We are reporting a distinct constitutive isoform of nitric oxide synthase that
      has been purified to homogeneity from human platelet cytosolic fractions.
      Purification involved ultra centrifugation at 100,000 x g followed by two
      sequential affinity chromatography procedures: adenosine 2',5'-bisphosphate
      (2',5'-ADP)-Sepharose and calmodulin Sepharose 4B. Purified enzyme appeared as a
      single band (approximately 80 kDa) under denaturing condition (SDS-PAGE). The
      native enzyme appears to be dimeric, since its molecular weight estimated by gel
      filtration was approximately 150 kDa. Enzyme activity was dependent on L
      arginine, NADPH and (6R)-5,6,7,8-tetrahydro-L-biopterine. Partially purified
      platelet NOS (100,000 x g supernatant) activity was sensitive to calmodulin
      antagonists and to the N omega-Monomethyl-L-arginine, a substrate analog of L
      arginine.

PMID- 7514443
TI  - Intracellular concentrations of inositol, glycerophosphoinositol and inositol
      pentakisphosphate increase during haemopoietic cell differentiation.
AB  - We have analysed the levels of soluble inositol metabolites in HL60 cells as they
      differentiate towards neutrophils in response to a combination of all-trans
      retinoic acid and granulocyte colony-stimulating factor and towards monocytes in
      response to 1 alpha-25-dihydroxyvitamin D3. In both cases, differentiation was
      accompanied by increases in intracellular inositol (Ins), glycerophosphoinositol
      (GroPIns) and inositol pentakisphosphate (InsP5) concentrations. [GroPIns]
      reached a peak early in the differentiation of both neutrophils and monocytes and
      subsequently fell to about double the starting level as the cells acquired mature
      characteristics, and [InsP5] rose later. Similarly, neutrophils derived in
      culture by the spontaneous differentiation of myeloid blast cells contained
      increased levels of Ins, GroPIns and InsP5 when compared to their parental blast
      cells. We have also compared the inositol metabolites present in two pairs of
      cell lines which are representative of immature and mature B and T lymphocytes.
      The mature cells again contained the higher levels of GroPIns and InsP5. We have
      previously demonstrated increases in Ins, GroPIns and Ins(1,3,4,5,6)P5 levels
      during the differentiation of HL60 cells towards neutrophils in response to DMSO
      and of GroPIns during the monocytoid differentiation of normal primitive myeloid
      blast cells in response to PMA. These observations suggest that deacylation of
      phosphatidylinositol by a phospholipase A/lysophospholipase pathway, forming
      GroPIns and probably also regulatory arachidonate metabolites, has some role in
      haemopoietic cell differentiation. The reasons why Ins(1,3,4,5,6)P5 and Ins
      accumulate during haemopoietic differentiation remain unknown.

PMID- 7514444
TI  - A G-protein beta subunit that is expressed in the central nervous system of the
      mollusc Lymnaea stagnalis identified through cDNA cloning.
AB  - We have cloned cDNA encoding a G-protein beta subunit from the central nervous
      system (CNS) of the mollusc Lymnaea stagnalis. The deduced protein is very
      homologous to other metazoan beta subunits. Thus, the Lymnaea CNS can be used as
      a model system to study beta gamma subunits in their native setting since its
      large neurons can be manipulated and studied relatively easily in vivo.

PMID- 7514445
TI  - Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates:
      biological efficacy study.
AB  - We have evaluated the biological efficacy of E1-deleted adenoviruses in baboons
      for lung-directed gene therapy of cystic fibrosis (CF). The experimental design
      attempted to simulate a phase I clinical trial with animals receiving a single
      dose of virus to an isolated pulmonary segment. A total of 14 animals divided
      into four groups, each of which received escalating doses of virus, were used.
      Individual animals were necropsied 4 and 21 days after gene transfer and tissues
      were carefully surveyed for gene expression. Expression of the transgene was
      localized primarily to the area into which it was infused; the efficiency of
      recombinant gene expression and the abundance of transgene sequences were
      proportional to dose and both diminished with time. Transgene expression was
      found predominantly in alveolar cells with patches of expression in the proximal
      and distal airway. Analysis of adenoviral protein expression within transgene
      expressing cells revealed infrequent expression of the E2a gene and no detectable
      expression of late genes (i.e., fiber protein). These results suggest that
      recombinant adenovirus can be used to transfer genes efficiently to the lung of
      nonhuman primates and that therapeutic strategies of cystic fibrosis may require
      repetitive administration with current vectors.

PMID- 7514447
TI  - Cell and gene therapy in Duchenne muscular dystrophy.
AB  - Experiments in mice have supported the idea of treating Duchenne muscular
      dystrophy (DMD) by implanting normal muscle precursor cells into dystrophin
      deficient muscles. However, similar experiments on DMD patients have had little
      success. Gene therapy for DMD, by introducing dystrophin constructs via
      retroviral or adenoviral vectors, has been shown to be possible in the mouse, but
      the efficiency and safety aspects of this technique will have to be carefully
      examined before similar experiments can be attempted in man. Direct injection of
      dystrophin cDNA constructs into mdx muscles has given rise to very low levels of
      dystrophin and this may be a possibility for the treatment of heart muscle.

PMID- 7514446
TI  - Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates:
      toxicity study.
AB  - In preparation for human trials of gene therapy for cystic fibrosis (CF), we
      performed a preclinical study of gene transfer into the lungs of baboons.
      Recombinant adenovirus vectors containing expression cassettes for human cystic
      fibrosis transmembrane conductance regulator (CFTR) and Escherichia coli beta
      galactosidase (lacZ) were instilled through a bronchoscope into limited regions
      of lung in 14 baboons. A detailed accounting of the extent, distribution, and
      duration of gene expression is contained in a companion article (Engelhardt et
      al., 1993b). In this article, we report the results of toxicity studies in which
      clinical laboratory tests, chest radiographs, and necropsy studies were used to
      detect adverse effects. The only adverse effect noted was a mononuclear cell
      inflammatory response within the alveolar compartment of animals receiving doses
      of virus that were required to induce detectable gene expression. Minimal
      inflammation was seen at 10(7) and 10(8) pfu/ml, but at 10(9) and more
      prominently at 10(10) pfu/ml, a perivascular lymphocytic and histiocytic
      infiltrate was seen. The intensity of inflammation increased between 4 and 21
      days. At its greatest intensity, there was diffuse alveolar wall damage with
      intra-alveolar edema. Airways were relatively spared, despite the intensity of
      alveolar inflammation. Clinical tests did not accurately reflect the presence of
      lung inflammation, with the exception of chest radiographs which revealed
      alveolar infiltrates, but only in regions of lung having the greatest intensity
      inflammation. We conclude that adenovirus-mediated gene transfer into the lungs
      of baboons is associated with development of alveolar inflammation at high doses
      of virus.

PMID- 7514448
TI  - Delayed morbidity and mortality of albumin/SV40 T-antigen transgenic mice after
      insertion of an alpha-fetoprotein/herpes virus thymidine kinase transgene and
      treatment with ganciclovir.
AB  - The alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and
      transcriptionally silent in adult tissues, but can be abnormally reactivated in
      hepatocellular carcinoma (HCC). We linked 7.6 kb of 5'-flanking DNA from the
      mouse AFP gene to the herpes simplex virus (HSV) thymidine kinase gene (tk), and
      a line of transgenic mice was produced that expressed TK in a pattern similar to
      endogenous AFP. When these AFP/tk transgenic mice were crossed to another
      transgenic line that develops multifocal HCC due to expression of a SV40 large T
      antigen transgene under regulation of the albumin promoter/enhancer complex, a
      significant delay of tumor progression could be achieved by administration of
      ganciclovir (GCV), a cytotoxic compound that is a substrate for phosphorylation
      by viral, but not mammalian, TK. Control animals carrying only the tk gene were
      unaffected by GCV treatment. These results illustrate the feasibility of
      prophylactic gene therapy for ablation of cancer, utilizing a strategy in which
      the tk gene is regulated by a promoter expected to be active only in tumor cells.

PMID- 7514449
TI  - High efficiency retroviral-mediated gene transduction into CD34+ cells purified
      from peripheral blood of breast cancer patients primed with chemotherapy and
      granulocyte-macrophage colony-stimulating factor.
AB  - The hematopoietic system has been one of the major targets for designing human
      gene therapy protocols. In the present system, we have transduced LNL6, one of
      the most commonly used retroviral vectors in gene therapy, into purified CD34+
      cells from peripheral blood of patients primed with chemotherapy and granulocyte
      macrophage colony-stimulating factor (GM-CSF). Purification of CD34+ cells was
      achieved by incubation with a murine anti-CD34 monoclonal antibody (9C5), and
      subsequently with paramagnetic microspheres (Dynal) coated with sheep anti-mouse
      IgG1 (Fc). The CD34+ cells were released from the beads by treatment with
      chymopapain. Flow cytometry analysis using the anti-CD34 antibody HPCA-2-FITC
      targeted at another epitope of CD34 showed that 78-97.5% of the cells thus
      purified were CD34+. After retroviral-mediated gene transfer, polymerase chain
      reaction (PCR) analysis revealed that 67-100% of the hematopoietic colonies
      contained the marker gene neo, indicating that CD34+ cells purified by
      immunomagnetic microsphere method from peripheral mononuclear cells primed with
      hematopoietic growth factors are highly susceptible to retroviral-mediated gene
      transfer. The expression of neo as determined by reverse transcription (RT)-PCR
      appeared to be unstable and not persistent. Taken together, our data suggest that
      LNL6 is a suitable vector for gene marking of hematopoietic progenitors but not
      for gene therapy protocols based on persistent gene expression.

PMID- 7514451
TI  - The hypercoagulable state in cancer patients: evidence for impaired thrombin
      inhibitions.
AB  - Activation of prothrombin and the subsequent reactions of thrombin with its
      substrates and its major inhibitors, antithrombin III (AT III) and heparin
      cofactor II (HC II), likely reflect both intravascular and extravascular
      coagulation. Several studies have reported increased in vivo coagulation in
      cancer. Whether the increased thrombin production in malignancy is accompanied by
      a corresponding increase in thrombin inhibition is unknown. This study quantified
      prothrombin fragment 1 + 2 (F1 + 2), thrombin-AT III (TAT), thrombin-AT III
      vitronectin (TAT.V), and thrombin-HC II-vitronectin (THCII.V) in the plasmas of
      healthy volunteers (n = 37); patients with localized solid tumours before
      treatment was initiated (n = 39); and five patients with non-Hodgkin's lymphoma,
      both before and during weekly chemotherapy. Two of the five non-Hodgkin's
      lymphoma patients developed deep venous thrombosis (DVT) during chemotherapy. In
      normal plasma, where the concentrations of the four parameters likely reflect
      haemostasis, the sum of TAT, TAT.V and THCII.V was 61% that of F1 + 2, compared
      with 30% in cancer plasmas. In addition, the mean +/- SEM of F1 + 2 in the
      plasmas of cancer patients (1.56 +/- 0.09 nM) was significantly elevated (P <
      0.001) when compared with healthy volunteers (0.89 +/- 0.06 nM). Eight weeks of
      chemotherapy increased the F1 + 2 and the binary TAT in plasmas of the non
      Hodgkin's lymphoma patients by approximately 1.5- and 2.9-fold, respectively.
      Thus, increased prothrombin activation in cancer patients, without corresponding
      increases in concentrations of thrombin-inhibitor complexes, raise the
      possibility that a significant portion of the thrombin generated in vivo escapes
      inhibition in cancer and contributes to the high risk of DVT in malignancy.

PMID- 7514450
TI  - Cystic fibrosis gene therapy using an adenovirus vector: in vivo safety and
      efficacy in nasal epithelium.

PMID- 7514453
TI  - Interaction of lipopolysaccharides with cells of immunological interest.
AB  - Recent progress has been made in understanding the diverse effects of bacterial
      endotoxin (LPS) on animal systems. Experiments from our laboratory, as well as
      those from several other groups, have provided strong evidence supporting the
      presence of different sites of interaction with LPS in cells of immunological
      interest. However, the sequence of expression of receptors, and their
      interrelations, are poorly understood. In this review, we summarize the
      essentials of these studies, with particular emphasis on experiments from our own
      laboratory. Our results suggest that the "positive" signals which trigger the
      activation of B lymphocytes and bone-marrow cells, as well as the "negative"
      signals which trigger macrophage desensitization and tolerance to LPS, might be
      delivered by sparsely represented and yet unidentified LPS receptors. The
      identification of these molecules would clarify the mechanisms involved in the
      immunostimulatory as well as in the pathophysiological effects of endotoxin, and
      should have significant impact upon potential therapeutic intervention in
      endotoxin-mediated disease.

PMID- 7514452
TI  - Antilipid A monoclonal antibody HA-1A decreases the capacity of bacterial
      lipopolysaccharide to activate human vascular endothelial cells by an immune
      adherence mechanism.
AB  - Human monoclonal IgM antibody HA-1A, which recognizes the lipid A component of
      bacterial lipopolysaccharide (LPS), has been shown to reduce mortality in Gram
      negative septicemia. The vascular endothelial lining of blood vessels, which
      controls leucocyte traffic and activation, as well as haemostatic balance, may be
      one of the primary targets of LPS action during sepsis. In earlier studies we
      have described HA-1A-induced immune adherence of LPS to complement receptors on
      erythrocytes, and showed that pre-incubation with HA-1A, in the presence of
      complement and red blood cells, markedly reduced LPS-induced cytokine production
      from peripheral blood mononuclear cells. In the present study, we measured the
      effect of immune adherence of LPS in the presence of HA-1A on the responses of
      cultured endothelial cells, and found that subsequent expression of adhesion
      molecules such as E-selectin, ICAM-1 and VCAM-1, and secretion of the cytokines
      interleukin-6 and granulocyte-macrophage colony stimulating factor were markedly
      reduced. Moreover, the ability of LPS to increase levels of tissue factor
      procoagulant activity on endothelial cells was markedly diminished by LPS immune
      adherence to HA-1A. This decrease in endothelial activation in response to LPS
      following immune adherence to HA-1A may play a significant role in the protective
      effect of HA-1A in vivo during the course of Gram negative sepsis.

PMID- 7514454
TI  - Regulation of the density of the stem cell factor receptor (c-kit) by tumor
      necrosis factor alpha on a human myeloid cell line.
AB  - The GM/SO cell line bears a high level of stem cell factor receptors (SCF-R) i.e.
      c-kit protein, and therefore constitutes a potential model for studying the
      regulation of this crucial receptor on myeloid cells. In this study we evaluated
      the effect of tumor necrosis factor alpha (TNF-alpha) on the expression of SCF-R
      by flow cytometry. In contrast to 1 hour of preincubation, the experiments
      carried out after 24 hours preincubation revealed that TNF-alpha, if added alone,
      reduced the density of SCF-R on GM/SO cells in a dose-dependent manner. However,
      if combined with GM-CSF, which per se downregulates the SCF-R on these cells as
      well, TNF-alpha antagonized the effect of GM-CSF and slightly increased the
      density of SCF-R. Yet the cells incubated for 24 hours in medium without
      cytokines invariably expressed a higher level of SCF-R than the cells incubated
      in the presence of TNF-alpha and GM-CSF, either alone or in combination. In
      contrast to these cytokines, stem cell factor (SCF), which was also tested
      simultaneously in all experiments, downregulated its own natural receptor on
      these cells also after a preincubation of 1 hour. Furthermore, prolonged exposure
      of GM/SO cells to TNF-alpha for 5-7 days yielded a monocyte-macrophage-like
      morphology of some cells as these cells displayed an apparent glass and plastic
      adherence. In contrast, no such morphological changes could be observed in the
      presence of GM-CSF or SCF.

PMID- 7514455
TI  - The cyclic nucleotide gated channel of olfactory receptor neurons.
AB  - Olfactory transduction proceeds through a G-protein coupled cascade that produces
      the ubiquitous second messenger cyclic AMP. The cyclic AMP causes a change in
      membrane potential by acting directly on an ion channel that allows cations to
      flow into the cell. This ion channel is one of a new family of ion channels that
      are activated by intracellular cyclic nucleotides. However, even though they are
      activated by binding a ligand their amino acid structure shows that they share a
      common ancestry with voltage activated channels, especially voltage dependent
      Ca2+ channels. In olfactory neurons these channels perform a critical role in the
      transduction of chemical information in the environment into changes in membrane
      electrical properties that are transmitted to higher order processing centers in
      the brain.

PMID- 7514456
TI  - Intensity coding in olfactory receptor cells.
AB  - Olfactory receptors code the concentration of stimulating molecules into an
      impulse frequency message. Patch-clamp recordings have now demonstrated, in the
      olfactory receptor cell membrane, a number of membrane conductances. Some of them
      are gated by odorants, in the cilia, and depolarize the cell through cAMP- or IP3
      sensitive channels, depending on the species. Other conductances are activated by
      membrane depolarization and/or an increased intracellular Ca2+ concentration;
      they participate in oscillating membrane potential changes during impulses and
      post-spike after-polarizations, and control the repetitive firing. Original data
      relative to the resting potential and the impulse frequency coding of the odorant
      concentration are presented.

PMID- 7514457
TI  - The Costello syndrome: report of a case and review of the literature.
AB  - A 5-year-old girl with the Costello syndrome is reported. Her clinical
      manifestations included growth and developmental delay, a distinct facial
      appearance with sparse and curly hair, nasal papillomata, and dark loose skin of
      the hands and feet. These manifestations, especially nasal papilloma, an age
      dependent anomaly, are distinct in the Costello syndrome.

PMID- 7514459
TI  - The hepatix extracorporeal liver assist device in the treatment of fulminant
      hepatic failure.

PMID- 7514458
TI  - The effect of activating mutations on dimerization, tyrosine phosphorylation and
      internalization of the macrophage colony stimulating factor receptor.
AB  - Oncogenic activation of the macrophage colony stimulating factor (M-CSF) receptor
      (c-Fms) requires mutation or truncation of the carboxyl terminus and specific
      amino acid substitutions in or near the fourth immunoglobulin (Ig)-like loop in
      the extracellular domain. Using a murine c-Fms system, we investigated the effect
      of C-terminal truncation, substitutions at amino acids 301 and 374 in the fourth
      Ig-like loop of the extracellular domain, or the combined mutations on individual
      steps in receptor activation. The mutations at amino acids 301 and 374 were
      necessary, but not sufficient, for receptor dimerization in the absence of M-CSF.
      Only receptors with a truncated C-terminus as well as the extracellular domain
      mutations dimerized efficiently in the absence of M-CSF, suggesting that the C
      terminus of c-Fms also regulates receptor oligomerization. Truncation of the C
      terminus alone did not cause receptor dimerization and did not activate the
      kinase enzymatic activity. Thus, truncation of the C-terminus did not activate
      receptor monomers in cis. Receptors with both a truncated C-terminus and the
      extracellular domain mutations underwent ligand-independent aggregation,
      transphosphorylation, and phosphorylation of cellular proteins, followed by rapid
      internalization and degradation. These results suggest that M-CSF binding to c
      Fms initiates activation by inducing conformational changes in both the
      cytoplasmic C-terminal domain and the fourth Ig-like loop of the extracellular
      domain, leading to the formation of stable receptor dimers.

PMID- 7514460
TI  - Topical FK506--clinical potential or laboratory curiosity?
AB  - Cyclosporine A (CsA) is an immunosuppressant that is efficacious in several
      inflammatory skin disorders. Its use is, however, limited due to systemic side
      effects. Topical forms of CsA have been tried but they do not seem to be
      effective presumably due to insufficient penetration to skin. Tacrolimus (FK506)
      is another immunosuppressant that has almost similar effects on the cellular
      level as CsA. FK506 is 10-100 times more potent than CsA and it has lower
      molecular weight. Recent studies suggest that topical FK506 penetrates human skin
      in amounts exceeding those of topical CsA. Topical FK506 also seems to suppress
      skin inflammation in man. These findings prompt for further clinical studies of
      efficacy and safety of topical FK506.

PMID- 7514461
TI  - The dominant form of hereditary palmoplantar keratoderma in the northernmost
      county of Sweden (Norrbotten).
AB  - The frequency of autosomal dominant inherited palmoplantar keratoderma (HPPK) in
      the northernmost county of Sweden (Norrbotten) is 0.55%. Histopathological
      examination of 91 biopsies from patients with the dominant form of HPPK revealed
      no case of epidermolytic PPK. This finding is in contrast to the results of a re
      examination of descendants of the original family published by Thost which showed
      the characteristic features of epidermolytic PPK, and re-evaluation of biopsies
      from other families has shown that it is the most frequent type. The existence of
      PPK type Unna-Thost in relation to epidermolytic PPK and to HPPK of the
      northernmost county of Sweden will be discussed. At the same time a revision of
      designation of this type is proposed. A dermo-epidermal mononuclear cell
      infiltrate belongs to the classical description of PPK Unna-Thost. It was shown
      that this cell infiltrate occurs significantly more often in patients with HPPK
      and dermatophytosis. Relapsing vesicular eruptions along the hyperkeratotic
      border are a clinical sign of the severity of dermatophyte infections. Such
      spongiotic vesicles together with a mononuclear cell infiltrate should be
      considered as eczematous reaction to dermatophytosis.

PMID- 7514462
TI  - Anti-GOR antibodies in lichen planus.
AB  - Anti-GOR antibodies characterize patients with autoimmune hepatitis type 2 who
      are all positive for antibodies to hepatitis C virus (HCV) and have low titers of
      anti-liver/kidney-microsomal (LKM1) antibody. The documented prevalence of anti
      HCV antibodies in patients with lichen planus (LP) and chronic liver disease
      (CLD) and their negativity for anti-LKM1 antibodies make them eligible for having
      anti-GOR antibodies. We studied such a possibility in 56 LP patients. Twenty of
      them had also CLD. Seven CLD patients without LP served as control. Overall,
      11/63 patients had anti-GOR antibodies. All of them were anti-HCV positive and
      had CLD. CLD patients with LP showed the same prevalence of anti-GOR antibodies
      as CLD patients without LP.

PMID- 7514463
TI  - Metallic stents in malignant biliary obstruction: results of a multicenter
      European study of 240 patients.
AB  - PURPOSE: In this retrospective multicenter study, the authors analyzed the
      clinical efficacy of different metallic stents in the palliative treatment of
      patients with neoplastic obstructive jaundice. PATIENTS AND METHODS: Two hundred
      forty patients were treated in four European centers. Causes of obstruction were
      pancreatic carcinoma (n = 84), biliary neoplasm (n = 99), metastases in hilar
      nodes (n = 34), primary or secondary liver tumors (n = 4), and other tumors (n =
      19). A total of 388 metallic stents were used: 300 Wallstents, 35 nitinol
      Strecker stents, 40 Gianturco-Rosch Z stents, and 13 tantalum Strecker stents.
      RESULTS: Overall 25- and 50-week survival rates were 42% and 16%, respectively;
      the 30-day mortality rate was 14.6%. Two deaths were related to the procedure
      (0.8%); 19 patients (8%) had major complications. The 25-week patency rate was
      significantly higher for the nitinol Strecker stents and the Wallstents (78% and
      67%, respectively) than for the Z stents and the tantalum Strecker stents (30%
      and 20%, respectively) (P < .01 and P < .001, respectively). Average patency was
      8.3, 5.9, 2.3, and 4.0 months, respectively. Reintervention due to stent
      obstruction was necessary in 53 patients. CONCLUSION: The Wallstent and the
      nitinol Strecker stents were the most effective in achieving long-term
      palliation. Patency was significantly affected by the level of obstruction but
      not by the type of obstructing tumor.

PMID- 7514464
TI  - Self-expandable nitinol stent for the management of biliary obstruction: long
      term clinical results.
AB  - PURPOSE: Technical characteristics and clinical efficacy of a new metallic stent
      for the management of biliary obstruction were investigated in a clinical study.
      PATIENTS AND METHODS: From February 1991 to January 1993, 35 self-expandable,
      nickel-titanium alloy wire-mesh stents (diameter, 10 mm; length, 6 cm) were
      placed in 19 patients with obstructive jaundice due to cholangiocarcinoma (n =
      6), pancreatic carcinoma (n = 5), lymph node metastasis to the liver hilum (n =
      5), gallbladder carcinoma (n = 2), and intraductal papillary mucosal hyperplasia
      (n = 1). RESULTS: Stent placement was successful in 18 of 19 patients. In one
      patient, stent dislodgement occurred after correct release; no other procedure
      related complications or deaths occurred within 30 days following the procedure.
      Two (11%) of the remaining 18 patients are alive at 11 months; 16 (89%) died
      after a mean survival of 7.4 months. Two of three patients with stent obstruction
      underwent repeated intervention. Adequate palliation from jaundice was achieved
      without further intervention in 83% of cases. The mean stent patency was not less
      than 7 months. CONCLUSION: Use of these metallic stents reestablished bile flow
      in the occluded biliary tree. Their efficacy and patency rate were also adequate.

PMID- 7514465
TI  - Human skeletal muscle has a voltage-gated proton current.
AB  - A voltage-gated proton current, IH, was studied with the whole-cell patch-clamp
      technique in human myotubes obtained from biopsies of human muscle. Studies of
      the reversal potential of IH during substitution of K+, Na+, Ca2+, Cl-, Cs+, and
      H+ in the extracellular solution indicated that protons were the major charge
      carriers of IH. This current is similar in many respects, but not identical, to
      the proton currents already described in other cell types. IH is activated by
      depolarization and it can be affected by extracellular pH. IH can be blocked by
      external divalent cations including Ca2+. This block is voltage-dependent, being
      more efficient at hyperpolarized than at depolarized voltages. The voltage
      dependent properties of IH and its ability to be affected by pH and extracellular
      Ca2+ suggest that IH might be used by muscle cells to extrude protons during
      action potentials.

PMID- 7514466
TI  - Circulating levels of insulin-like growth factor-I and -II, and IGF-binding
      protein-3 in inflammation and after parathyroid hormone infusion.
AB  - In order to assess if the anabolic action of PTH is related to changes in
      circulating levels of insulin-like growth factor-I and -II (IGF-I and -II), and
      IGF binding protein 3 (IGFBP-3), 24 h of PTH infusion was performed in healthy
      women and in patients with rheumatoid arthritis (RA), a state where both bone
      metabolism and PTH secretion is influenced by the inflammatory activity. The
      patients with RA had lower basal levels of both IGF-I and -II than the healthy
      controls (P < 0.05). In neither group did the IGFs change after 24 h of PTH
      administration, while IGFBP-3 was significantly increased in the healthy controls
      (4600 +/- 1200 to 5750 +/- 2200 micrograms/l, P < 0.05). IGFBP-3 was not affected
      by PTH infusion in patients with RA when the disease had high activity, but when
      inflammation had subsided they responded with a similar increase in IGFBP-3 as
      the control group and basal IGF-I and -II levels were normalised. Since IGFBP-3
      can enhance the anabolic action of IGF-I, increased IGFBP-3 levels after PTH
      infusion may reflect a mechanism by which PTH is anabolic for bone. Inflammation
      may inhibit bone formation via decreased serum levels of IGFs and blocked IGFBP-3
      response to PTH.

PMID- 7514467
TI  - [A new approach to assessing the role of various organs in adapting to high
      altitude hypoxia].

PMID- 7514468
TI  - Sensitivity of 3T3 cells to low serum concentration and the associated problems
      of serum withdrawal.
AB  - The sensitivity of cells to serum deprivation depends upon whether they are
      transformed. Most supplies of 3T3 cells are of this type and are considerably
      less sensitive than untransformed cells. In addition, the apparently simple
      manoeuvre of reducing serum levels has considerable effects on cell fragility,
      viability, growth rate and metabolism, which were found to be due to small
      changes in pH, substrate availability, cell density and other parameters, many of
      which cannot be attributed to the absence of growth factors from the medium.
      Supplementation of medium with bovine serum albumin (BSA) to compensate for low
      normal serum protein did not aid growth nor offset the disturbances caused by low
      serum levels themselves. Problems associated with the altered precursor
      availability for DNA, RNA and protein synthesis are also discussed.

PMID- 7514469
TI  - Transfected Chinese hamster ovary cells as a model system for cytokine
      immunocytochemistry and in situ hybridisation.
AB  - The presence of cytokine producing cells is most easily revealed by techniques
      measuring the secreted cytokines in culture supernatants or body fluids. However,
      these techniques only measure the bulk cytokine release by a given, often mixed
      cell population. To demonstrate cytokine production at the single cell level,
      immunocytochemistry (ICC) and in situ hybridisation (ISH) are now widely used
      techniques. To establish these techniques, an easily accessible model system is
      needed which permits the evaluation of different ICC and ISH protocols. It can be
      used to demonstrate the specificity of the antibodies and may serve as a positive
      control for samples of unknown cytokine content. Here we propose the use of
      Chinese hamster ovary (CHO) cells transfected to express one specific cytokine as
      such a model system. Its usefulness is demonstrated by the characterisation of
      six monoclonal antibodies to human interleukin-4 and the establishment of two in
      situ hybridisation protocols.

PMID- 7514470
TI  - Clinical experience with transurethral microwave thermotherapy for chronic
      nonbacterial prostatitis and prostatodynia.
AB  - Chronic prostatitis and prostatodynia are troublesome disorders that are not
      responsive to any kind of treatment. Patients with treatment-resistant chronic
      nonbacterial prostatitis (n = 61) or prostatodynia (n = 17) for longer than 3
      years underwent a single 1-hour session of transurethral microwave thermotherapy
      (TUMT) using the Prostatron. Complete symptom disappearance was obtained in 23%
      of patients and a partial response in 43%. Of the patients with prostatitis, 46%
      showed normalization and 31% an improvement of the leukocyte count in expressed
      prostatic secretion. In patients with prostatodynia, the corresponding figures
      were 35% and 41%. Most complications were temporary, but there was one case of
      epididymitis and one of reduction in the volume of the ejaculate. TUMT is well
      tolerated and safe, and it is effective in relieving the symptoms of many
      patients with nonbacterial prostatitis or prostatodynia. The possible adverse
      effects on fertility and urinary continence require further study.

PMID- 7514471
TI  - Stent of shape-memory alloy for urethral obstruction caused by benign prostatic
      hyperplasia.
AB  - Dilation and positioning a stent in the prostatic urethra have become important
      alternatives for the management of benign prostatic hyperplasia (BPH), but both
      have significant drawbacks, namely the need to repeat the treatment in the former
      case and the conflict between the introducing means and the generation of
      sufficient expansile force in the latter case. A spiral of a Chinese titanium
      nickel alloy with shape memory was implanted in 25 patients with BPH using a self
      made coaxial sheath. With a follow-up of 3 to 20 months, the success rate is 92%.
      There has been no encrustation or migration of the spirals. We deem the spiral of
      this shape-memory alloy to be a good alternative in patients with BPH who are
      unfit for surgery.

PMID- 7514472
TI  - Treatment of ureteral stones by extracorporeal shock wave lithotripsy: with
      ureteral catheter or in situ?
AB  - Many authors recommend that stone manipulation or catheter placement be attempted
      before SWL of ureteral stones. We tried to insert ureteral catheters before SWL
      on the unmodified Dornier HM3 machine in all patients treated for solitary
      ureteral stones between April 1986 and December 1991, succeeding in 77.5% (n =
      395) of those for whom adequate follow-up is available for analysis. The stone
      free rates with SWL alone in the series of 510 patients were 93% in patients with
      catheters and 75% in patients without catheters. An additional 6% of the patients
      in both groups became stone free with the aid of ureteroscopy. Eventually, only
      0.5% of the patients with a catheter and 1.7% of the patients without a catheter
      had residual fragments. Among patients with a ureteral catheter after any
      procedure, 58.7% had no need for pain relief medication and no fever; the figure
      in the patients treated without a catheter was 74.4%. Although the success rate
      of SWL for ureteral stones is higher with a ureteral catheter in place, the
      incidence of complications also is higher. We recommend trying in situ SWL
      initially for patients with a ureteral stone.

PMID- 7514473
TI  - [Prognostic factors in prostate cancer. Review of the literature and future
      perspectives].

PMID- 7514474
TI  - [Vaginal metastasis from cancer of the kidney].
AB  - Authors report a new case of vaginal metastasis from renal cell carcinoma. Their
      main characteristics are reviewed. Possible retrograde venous spread and genital
      vein ligation prior to manipulation of the kidney are highlighted.

PMID- 7514475
TI  - [ELISA kits for detection of anti-HCV antibodies. "Viral Hepatitis" Working Group
      of the French Society of Blood Transfusion].

PMID- 7514476
TI  - Immunohistochemical localization of gap junction protein channels in hamster
      sinoatrial node in correlation with electrophysiologic mapping of the pacemaker
      region.
AB  - INTRODUCTION: Gap junction proteins are thought to form the low resistance
      pathways that connect neighboring cells within the sinoatrial node, and to
      mediate pacemaker synchronization. METHODS AND RESULTS: We have carried out
      microelectrode mapping experiments of the hamster sinoatrial region to localize
      the primary pacemaker area for subsequent light, electron, and immunofluorescence
      microscopic studies aimed at testing the hypothesis that the major cardiac gap
      junction protein (connexin43) is present in such an area. The site of earliest
      activation is unifocal and the pattern of activation, obtained by multiple
      sequential microelectrode recordings of the sinoatrial region, is qualitatively
      similar to that previously described for other species. However, quantitatively,
      the impulse transmission time from the primary pacemaker area to the crista
      (sulcus) terminalis in the hamster sinoatrial node is about 50% briefer than that
      of the guinea pig and five times faster than that of the rabbit.
      Immunolocalization studies in the hamster sinoatrial node using anti-connexin43
      antisera demonstrated specific staining at the areas of cell-to-cell apposition
      and suggested that the apparently high degree of electrical coupling in this
      tissue is the result of abundant connexin43 expression. The immunofluorescence
      data were supported by light microscopic studies, which demonstrated the typical
      morphologic characteristics of sinus nodal cells in the pacemaker area. In
      addition, an electron microscopic study of the sinoatrial region revealed the
      presence of gap junctions in the junctional complex at areas of cell-to-cell
      contact. CONCLUSION: Our results demonstrate that cells in the sinoatrial region
      of the hamster heart are electrically well coupled and strongly suggest that such
      coupling is mediated by gap junctional channels formed by connexin43.

PMID- 7514477
TI  - An immunohistochemical study of the extracellular matrix in oral squamous cell
      carcinoma and its association with invasive and metastatic potential.
AB  - The expression of extracellular matrices (ECMs) laminin (LN), type IV collagen
      (IV C), heparan-sulphate proteoglycan (HS-PG), fibronectin (FN), tenascin (TN),
      decorin and vitronectin (VN) was examined immunohistochemically in 112 primary
      tumours and 29 metastatic cervical lymph nodes in oral squamous cell carcinoma
      (OSCC). In highly invasive primary tumours, the expression of LN, IV C and HS-PG
      in the basement membrane along the tumour-stroma borderline and the expression of
      decorin and VN in the tumour stroma at the invasive site were all significantly
      decreased. The expression of FN and TN in the tumour stroma at the same site was
      markedly increased. In peritumour stroma in metastatic lymph nodes, LN, IV C, HS
      PG, decorin and VN were weakly expressed, while FN and TN were strongly
      expressed. Thus, the staining pattern of the ECMs in the metastatic lymph nodes
      was similar to that in highly invasive primary tumours. Furthermore, in primary
      tumours of metastatic cases, the expression of LN, IV C, HS-PG, decorin and VN
      obviously decreased, while the expression of FN and TN increased when compared
      with those of the non-metastatic cases. The investigation of ECMs in OSCC was
      valuable in predicting tumour behaviour.

PMID- 7514478
TI  - Immunohistochemical reaction patterns of keratins in MNNG-induced shrew
      oesophageal carcinomas.
AB  - The distribution of keratins in N-methyl-N'-nitro-N-nitrosoguanidine-induced
      oesophageal carcinomas in shrews was tested immunohistochemically, using a panel
      of seven different monoclonal antibodies. The studies were done on methacarn
      fixed paraffin-embedded tissue, using the labelled streptavidin biotin method,
      and the relationship between morphological characteristics and keratin reaction
      patterns in carcinomas was analysed and compared with that in adjacent "normal"
      oesophageal epithelium. In the normal oesophageal epithelia, KL1, AE1, AE3,
      CK8.12, and CK4.62 stained suprabasal cells, 312C8-1 reacted to basal cells, and
      KS-1A3 labelled all epithelial cells. In squamous cell carcinomas, almost all the
      cancer cells were labelled strongly by 312C8-1 and weakly by KS-1A3, while a few
      cells in the centres of the keratinized foci were stained by KL1, AE1, AE3,
      CK8.12, and CK4.62. Like human oesophageal carcinomas, shrew oesophageal
      carcinomas maintain expression of human keratin 14, as determined by 312C8-1. The
      expression of human keratin 13, as determined by KS-1A3, was down-regulated.

PMID- 7514479
TI  - Effects on movement of surgical incisions into the human spinal cord.
AB  - In 44 patients having cordotomies for relief of the pain of cancer, a correlation
      was made between the location and extent of the incision in the spinal cord and
      the motor state. Post-mortem histological examination of the spinal cord was
      carried out in all areas. An incision cutting through one anterior quadrant of
      the cord at any segmental level could be made without causing any disturbance of
      motility. An incision in the thoracic segments cutting through the anterior half
      of the cord could be made without causing any disturbance of motility. This fact
      implies that tracts in the posterior half of the cord can supply the input from
      the brain necessary for the maintenance of functions normally mediated by tracts
      in the anterior half of the cord. The more posterior the incision reached in the
      posterolateral column, the greater were the defects in motility. A large
      unilateral lesion dividing most of the lateral corticospinal tract, and the
      descending fibres anterior to it, caused flaccid paralysis of the ipsilateral
      lower limb. Voluntary movements started to return within 5 h. An incision in the
      thoracic cord cutting through one lateral corticospinal tract and 85-90% of the
      opposite tract and reticulospinal fibres anterior to that tract caused total
      paralysis of the lower limbs. Recovery ensued over 2 months so that the patient
      eventually walked, though with severe spastic paraparesis. Recovery of some
      flexor and extensor movements of the ipsilateral fingers and toes occurred within
      6 h of an incision being made in the upper cervical cord that divided the lateral
      corticospinal tract unilaterally. Division of only the anterior fibres of the
      lateral corticospinal tract above the cervical enlargement did not affect the
      motility of the ipsilateral upper limb. It is concluded that in the more cranial
      segments of the spinal cord, corticospinal fibres destined for the upper limb are
      in the more posterior part of the tract. Correlation of the clinical with the
      histological evidence of a lesion of the lateral corticospinal tract was carried
      out. When it was deduced on the clinical evidence that the tract was damaged,
      this was always found to be correct. On the other hand, the tract might show
      histological evidence of damage without manifesting any evidence of a lesion. The
      Babinski response was found, in general, to occur with lesions of the lateral
      corticospinal tract and not with lesions elsewhere in the cord.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7514480
TI  - Effects of angiotensin II on dopamine and serotonin turnover in the striatum of
      conscious rats.
AB  - This study was designed to evaluate the functional significance of angiotensin II
      (Ang II) receptors identified by previous receptor autoradiography studies to be
      located presynaptically on terminals of dopaminergic neurones projecting to the
      striatum. Microdialysis was performed in the striatum of conscious freely moving
      rats and dopamine and serotonin metabolites measured by HPLC with electrochemical
      detection. During perfusion with artificial CSF, the major extracellular dopamine
      metabolite identified was DOPAC with smaller concentrations of HVA. When Ang II
      (1 microM) was introduced into the dialysis perfusion medium, DOPAC output
      increased markedly, peaking at 219%, and returned to control with vehicle
      perfusion during the recovery period. This increase in DOPAC output with Ang II
      was completely blocked by co-administration of the AT1 selective antagonist,
      Losartan (1 microM). Administration of Losartan alone led to a significant (16%)
      depression of DOPAC output relative to vehicle, suggesting that dopamine release
      is under a tonic facilitatory influence of Ang II via the AT1 receptor subtype.
      Parallel, but smaller changes were seen with HVA outputs. During Ang II perfusion
      the output of HVA was elevated 34-79% of that in vehicle-treated rats and this
      effect was completely abolished by concomitant administration of Losartan. As was
      observed with DOPAC output, administration of Losartan alone led to a 13-24%
      depression of HVA output compared to vehicle perfusion. When nomifensine (10
      microM) was included in the infusion fluid, dopamine was clearly measurable. Ang
      II perfusion increased the levels of dopamine to 225%. Values returned towards
      baseline during the recovery period. Ang II administration also increased (by 15%
      and 55%) the levels of the major serotonin metabolite, 5HIAA.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7514481
TI  - An in vitro system for the study of slow axonal transport.
AB  - Here we present a model system which for the first time permits studies of slow
      axonal transport in vitro. Axonally transported proteins of rat vagus nerves were
      radiolabelled with [35S]methionine in the nodose ganglion in vitro and were
      incubated for up to 3 days in culture medium. Slowly transported proteins were
      analyzed by one- and two-dimensional polyacrylamide gel electrophoresis and
      identified on Western blots of two-dimensional gels with antibodies to actin and
      alpha-tubulin. The system will be valuable for pharmacological analysis of the
      mechanisms of slow transport.

PMID- 7514482
TI  - Differences in Fluorogold and wheat germ agglutinin-horseradish peroxidase
      labelling of bladder afferent neurons.
AB  - Rat urinary bladder afferent neurons were significantly smaller (34%) when
      labelled with Fluorogold (FG) than when labelled with wheat germ agglutinin
      horseradish peroxidase (WGA-HRP). This study showed that this difference was due
      to an artifact of tissue processing (ethanol dehydration) and was not due to
      uptake and transport of the two tracers by two different subpopulations of
      bladder afferents.

PMID- 7514484
TI  - Acidic fibroblast growth factor facilitates generation of long-term potentiation
      in rat hippocampal slices.
AB  - In the present study, effects of acidic fibroblast growth factor (aFGF, 0.5-2.5
      ng/ml) on synaptic transmission were investigated in rat hippocampal slices.
      Stimulation was applied to Schaffer collateral/commissural afferents and evoked
      spikes were recorded in CA1 pyramidal cell layer. Continuous perfusion of slices
      with aFGF slightly decreased the basal amplitude of the spikes and significantly
      increased the paired-pulse facilitation. When brief tetanic stimulation (7
      impulses at 100 Hz) was applied 30 min after the perfusion of aFGF, aFGF-treated
      slices enhanced the magnitude of short-term potentiation after the tetanus and
      facilitated the generation of long-term potentiation. aFGF also enhanced post
      tetanic potentiation directly after the tetanus. These effects of aFGF were dose
      dependent. The enhancement of short-term potentiation and facilitation of the
      generation of long-term potentiation were not evident when aFGF was applied with
      or 10 min after the tetanus. The results suggest that aFGF is implicated in
      modulation of synaptic efficacy and can activate some mechanisms related to the
      generation of long-term potentiation.

PMID- 7514483
TI  - Nitric oxide mediates the stimulation of luteinizing-hormone releasing hormone
      release induced by glutamic acid in vitro.
AB  - Previous experiments from our laboratory have indicated that LHRH release is
      controlled in vivo and in vitro by NO. Since glutamic acid, the major excitatory
      transmitter in the brain, has been shown to release LHRH, we wished to determine
      whether or not this LHRH release was mediated by NO. Consequently, arcuate-median
      eminence explants from normal male rats were incubated in vitro in Krebs-Ringer
      bicarbonate glucose (KRBG) media in a Dubnoff metabolic shaker for a
      preincubation period of 30 min. Fresh media were added containing the substances
      to be tested and incubation was continued for 30 min. Sodium nitroprusside (NP,
      500 microM), which releases NO spontaneously, stimulated the release of LHRH,
      which indicates that NO can release LHRH. Glutamic acid (10 mM) also produced a
      robust release of LHRH, and this release was blocked by the inhibitor of NO
      synthase, NG-monomethyl-L-arginine (NMMA). Furthermore, the release of LHRH
      induced by glutamic acid was prevented by the addition of hemoglobin (20
      micrograms/ml), a scavenger of NO, which would remove the NO released by the
      action of glutamic acid. The results indicate that glutamic acid stimulated LHRH
      release is induced by NO.

PMID- 7514485
TI  - Effects of intranigral injections of colchicine on the expression of some
      neuropeptides in the rat forebrain: an immunohistochemical and in situ
      hybridization study.
AB  - In the present study, we describe the neurochemical effects of intranigral
      injections of colchicine in the rat forebrain using immunohistochemistry and in
      situ hybridization. The observations on the injected side are compared to the
      contralateral one and to the sham-operated rats. We demonstrate that such
      injections are able to strongly enhance the immunoreactivity for Met-enkephalin
      (ME), substance P (SP) and neuropeptide Y (NPY) in numerous nerve cell bodies of
      the limbic system (injected side), whereas the levels of the corresponding mRNAs
      are differently modified according to the region examined. A clear correlation
      between the enhancement of the immunostaining for ME and SP and that of the
      preproenkephalin (PPA) and preprotachychinin gene transcripts was observed in
      neuronal perikarya of the medial amygdaloid nucleus (SP), of the dorsolateral
      hypothalamus (ME) and of the ventromedial hypothalamic nucleus (SP). These
      observations are interpreted as an induction--or increased expression--of
      neuropeptide genes in neuronal perikarya postsynaptic to nerve fibers originating
      in the midbrain and brain stem. In this case, colchicine is thought to block the
      electrophysiological activity of ascending nerve fibers (anterograde and
      postsynaptic effect). In the case where the enhancement of the immunoreactivity
      for the studied neuropeptides was associated with no change or a decreased
      expression of the corresponding genes in the same brain areas, colchicine may
      have blocked the axoplasmic transport of peptides in nerve fibers projecting to
      the midbrain and/or brain stem (6). This may result in a retrograde accumulation
      of peptides in the nerve cell bodies of origin and, eventually, in a negative
      feedback regulation of the corresponding encoding genes in these perikarya
      (retrograde and presynaptic effect of colchicine). The drastic behavioral effects
      of bilateral intranigral injections of colchicine, on ingestive behavior in
      particular, have been studied in a following paper.

PMID- 7514486
TI  - Anatomical and physiological relationships between the anterior cerebellar vermis
      and the pontine parabrachial nucleus in the rabbit.
AB  - The anatomical connections between the midline cerebellum and the pontine
      parabrachial nucleus (PBN) were investigated in the rabbit using anterograde and
      retrograde axonal transport techniques. Small injections (20-50 nl) of cholera
      toxin conjugated to horseradish peroxidase (CT-HRP) or wheat germ agglutinin
      conjugated HRP (WGA-HRP) into the cortex of the anterior cerebellar vermis
      resulted in retrograde and anterograde-like label in the PBN. Focal injections of
      tracer into the PBN resulted in anterogradely labeled processes in the ACV and
      retrogradely labeled a small, but distinct group of Purkinje cells within the
      anterior vermis. Focal injections into the rostral fastigial nuclei (FN) resulted
      in anterograde-like label in the PBN, and PBN injections labeled FN neurons.
      Furthermore, the projection from the PBN to ACV is effective in driving
      cerebellar neurons as electrical microstimulation of the PBN evoked short
      latency, phasic responses in ACV Purkinje cells. These experiments generated
      anatomical and physiological evidence for the existence of a neuroanatomical
      circuit connecting the midline cerebellum (ACV, FN) with the PBN, that may serve
      as a functional interface between the midline cerebellum and other brain stem
      nuclei with cardiovascular function, particularly with respect to the midline
      cerebellar role in classically conditioned cardiovascular responses.

PMID- 7514487
TI  - Administering mercy: the ethics of pain management.

PMID- 7514488
TI  - On "The ethics of pain management".

PMID- 7514489
TI  - Chironomidae haemoglobin Chi t I--characterization of an important inhalant
      allergen.

PMID- 7514490
TI  - Cefotiam-induced IgE-mediated occupational contact anaphylaxis of nurses; case
      reports, RAST analysis, and a review of the literature.
AB  - Cefotiam (CTM) is one of the most popular cephem antibiotics in Japan. Recently
      we experienced two cases of nurses with CTM-induced contact anaphylaxis. When
      they were preparing drip infusions of antibiotics or working around other nurses
      doing so, they suddenly fell into shock with other symptoms such as flushing,
      urticaria, abdominal distress, vomiting, dyspnoea and/or loss of consciousness.
      The symptoms never occurred after they avoided exposure to CTM. Passive cutaneous
      or open patch tests were positive for CTM. Histamine release was induced by CTM
      from washed leucocytes. RAST analysis using CTM-human serum albumin-coupled discs
      showed high % RAST count, suggesting that these reactions were mediated by IgE
      antibodies. A RAST inhibition test suggested that the methyl-thiotetrazole side
      chain was the main antigenic determinant. Both patients had hand dermatitis that
      had appeared preceding the episodes of anaphylaxis. Although the dermatitis had
      been resistant to treatments, it also disappeared after they avoided exposure to
      CTM. It seemed likely that it was also induced or exacerbated by CTM and
      facilitated the penetration of CTM to cause anaphylaxis. The literature is also
      reviewed.

PMID- 7514491
TI  - Aerosolized acetaldehyde, but not ethanol, induces histamine-mediated
      bronchoconstriction in guinea-pigs.
AB  - It was reported that ethanol-induced bronchoconstriction was associated with
      elevated serum levels of acetaldehyde and histamine in Japanese asthmatic
      patients, but there is no study to investigate the airway response to
      acetaldehyde. We performed this animal study to test the hypothesis that
      acetaldehyde has the bronchospastic action via histamine release. First, we
      investigated the airway response to ascending doses (31.3, 62.5, 125, and 250 mM)
      of inhaled ethanol or acetaldehyde in guinea-pigs. Secondly, guinea-pigs
      pretreated with intraperitoneal injection of saline or 20 mg/kg diphenhydramine
      inhaled acetaldehyde. Finally, guinea-pigs pretreated with intraperitoneal
      injection of saline or 0.5 mg/kg atropine sulfate inhaled acetaldehyde.
      Inhalation of acetaldehyde, but not ethanol, caused bronchoconstriction in a dose
      dependent manner. The bronchoconstriction induced by inhaled acetaldehyde was
      completely prevented by pretreatment with diphenhydramine. Atropine had no
      preventing effect against the acetaldehyde-induced bronchoconstriction. In
      conclusion, acetaldehyde has the bronchospastic action via histamine release in
      guinea-pigs. It is suggested that histamine H1-antagonists may be available for
      preventing alcohol-induced asthma.

PMID- 7514492
TI  - Polyamines prevent DFMO-mediated inhibition of angiogenesis.
AB  - Tumor growth mainly depend on formation of new blood vessels. DFMO (alpha
      difluoromethylornithine), an inhibitor of polyamine biosynthesis, inhibits tumor
      growth in many animal tumors. Our investigation was to evaluate the requirement
      of polyamines for induction of angiogenesis by tumor cells and spleen lymphocytes
      from tumor-bearing mice. In this regard, we have added DFMO to cell cultures. The
      neovascular response induced either by tumor cells or spleen lymphocytes was
      completely abrogated. This inhibition could be reversed by the addition of
      exogenous putrescine. These findings suggest that the effect of DFMO on
      angiogenesis is, in part, mediated by the inhibition of polyamine biosynthesis.

PMID- 7514493
TI  - Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera
      from breast, pancreatic, and colon cancer patients.
AB  - Using synthetic peptides 60,80, and 105 residues long, corresponding to 3, 4, and
      5.25 tandem repeats of human mucin MUC-1 protein core, as antigens in a solid
      phase enzyme-linked immunosorbent assay, we screened sera from 24 breast cancer
      patients, 10 colon cancer patients, and 12 pancreatic cancer patients, at various
      stages of disease, for the presence of mucin-specific antibodies. The 105-residue
      peptide was superior in allowing detection of high levels of anti-mucin
      antibodies in 10.9% of sera in each cancer group. Another 4.3% showed
      intermediate reactivity. Lower levels of detection were achieved with the 80
      residue peptide, and no specific reactivity was detectable with the 60-residue
      peptide. Anti-mucin antibodies were previously undetectable when this assay was
      performed with purified whole mucin or short synthetic peptides. The presence or
      absence of antibody did not correlate with the levels of circulating mucin or
      stage of disease. One highly reactive serum sample was used to identify more
      precisely the epitope on the long synthetic peptide to which the reactivity was
      directed. The reactivity of this serum specific for the 105-residue peptide was
      blocked by a 9-residue peptide from the NH2-terminal region of the 20-residue
      tandem repeat containing the previously identified immunogenic epitope APDTRP.
      Another 9-residue mucin peptide, from the COOH-terminal region of the tandem
      repeat which does not contain the APDTRP epitope, had no effect. All the mucin
      specific reactivity was found to be of the IgM isotype, indicating a helper T
      cell-independent response, unusual for an antibody against a peptide epitope, but
      not unexpected for tandemly repeated epitopes.

PMID- 7514494
TI  - Transfection with a bcl-2 expression vector protects transplanted bone marrow
      from chemotherapy-induced myelosuppression.
AB  - The use of cytokines such as granulocyte-colony-stimulating factor (G-CSF) to
      ameliorate chemotherapy-induced myelosuppression may not only stimulate the
      recovery of normal hematopoietic cells but may also enhance the proliferation of
      the tumor cells with functional receptors for these cytokines. In this study, we
      show that administration of recombinant human (rh) G-CSF decreased the in vitro
      and in vivo cytotoxic effects of Adriamycin or etoposide on L1210 murine leukemic
      cells with receptors for rhG-CSF. Transplantation of bone marrow cells expressing
      high levels of bcl-2 from a retroviral construct [MPZenNeo(bcl-2)] (bcl-2-BMT)
      did not decrease the in vivo cytotoxic effect of etoposide on L1210 cells, but
      enabled recovery of myelopoiesis following etoposide-induced myelosuppression to
      almost the same extent as did the administration of rhG-CSF. These findings
      suggest the possibility that bcl-2 transfection could be used to protect
      transplanted bone marrow from chemotherapy-induced myelosuppression on behalf of
      administration of rhG-CSF, in case of treatment of tumors with functional
      receptors for rhG-CSF.

PMID- 7514496
TI  - Coexpression of the c-kit receptor and the stem cell factor in gynecological
      tumors.
AB  - The protooncogene c-kit encodes a transmembrane receptor-type tyrosine kinase
      which belongs to the beta-PDGER/CSF-1 receptor tyrosine kinase family. The
      interaction between c-kit receptor and its corresponding ligand, stem cell factor
      (SCF), has been suggested to be involved in embryogenesis as well as
      carcinogenesis via the autocrine/paracrine system. In the present study, cancer
      cell lines and normal/benign/malignant tissues of the human female genital tract
      were examined for the expression of both c-kit and SCF by Northern blot and
      immunohistochemical analyses. Two of 16 cell lines showed mRNA expression of both
      c-kit and SCF, while 2 and 12 cell lines expressed c-kit and SCF, respectively.
      In tissues, several cases of malignant tumors, including three cervical cancers,
      one ovarian cancer, and one ovarian immature teratoma, expressed mRNA of both c
      kit and SCF. In normal tissues, squamous epithelium expressed SCF
      immunohistochemically, while c-kit protein was detected only in melanocytes. Some
      tissues of malignant tumors, one squamous cell carcinoma of the cervix, two small
      cell carcinomas of the cervix, two serous adenocarcinomas of the ovary, and two
      immature teratomas of the ovary, expressed both c-kit and SCF proteins
      immunohistochemically. It is also notable that c-kit protein was expressed only
      in malignant germ cells of dysgerminomas, while SCF was expressed in the
      connective tissues surrounding germ cells. The present study suggests that the c
      kit/SCF system may play an important role in the carcinogenesis of the female
      genital tract.

PMID- 7514495
TI  - Hormonal regulation of insulin-like growth factor II and insulin-like growth
      factor binding protein expression by breast cancer cells in vivo: evidence for
      stromal epithelial interactions.
AB  - Insulin-like growth factors (IGFs) I and II are potent mitogens for breast cancer
      cells. Their proliferative activity is likely to be influenced by their binding
      proteins (IGFBPs), a family of newly identified proteins. We report here on the
      in vivo hormonal regulation of mRNAs for IGF-II and IGFBPs in the N
      nitrosomethylurea-induced rat mammary tumor, a well-established model of hormone
      responsive mammary cancer. IGF-II mRNA levels tended to decrease in regressing
      tumors following ovariectomy, and they markedly increased upon reactivation of
      tumor growth with hormone repletion. Ovariectomy induced a drastic increase in IG
      FBP-6 mRNA which was reversible with hormone repletion. Similar but more modest
      changes were observed with IGFBP-2 mRNA. In contrast, IGFBP-3 and IGFBP-4 mRNAs
      tended to decrease with ovariectomy and increase with hormone repletion. These
      latter effects, however, were modest, variable, and not statistically
      significant. In situ hybridization analysis revealed that IGF-II, IGFBP-5, and
      IGFBP-6 mRNAs were localized in the stromal component of the tumor, whereas IGFBP
      2 mRNA was expressed by epithelial cells. We conclude that hormonal regulation of
      IGFBP expression is heterogeneous, thus suggesting divergent biological functions
      for these peptides. Our data also emphasize the importance of potential stromal
      epithelial interactions in the control of breast cancer cell proliferation by
      IGFs.

PMID- 7514497
TI  - The structure of the lipopolysaccharide O antigen from Yersinia ruckeri serotype
      01.
AB  - The O antigen obtained from the lipopolysaccharide of Yersinia ruckeri serotype
      01, by mild acid hydrolysis, is composed of a branched tetrasaccharide repeating
      unit containing 2-acetamidino-2,6-dideoxy-L-galactose (L-FucAm), 2-acetamido-2
      deoxy-D-glucose (D-GlcNAc), and 7-acetamido-3,5,7,9-tetradeoxy-5-(4
      hydroxybutyramido)-D-glycero-L -galacto- nonulosonic acid (L-Sug). Partial
      hydrolysis of the O antigen with 0.1 M HClafforded a trisaccharide and a
      tetrasaccharide having nonulosonic acid at their reducing ends. Cleavage of the O
      antigen with anhydrous methanolic hydrogen fluoride afforded the methyl glycoside
      derivatives of a trisaccharide and a tetrasaccharide. 1H and 13C NMR analysis,
      including 1H-13C heteronuclear multiple bond correlation spectroscopy to locate
      the N-acyl substituents, together with mass spectrometric analysis of the above
      oligosaccharides, allowed the structure of the O-specific polysaccharide to be
      assigned as: [formula: see text].

PMID- 7514498
TI  - Teaching dentistry in the 21st century.

PMID- 7514499
TI  - Distribution and colocalization of nitric oxide synthase and NADPH-diaphorase in
      adrenal gland of developing, adult and aging Sprague-Dawley rats.
AB  - The distribution and colocalization of nitric oxide synthase and nicotinamide
      adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase) was investigated in
      the adrenal gland of developing, adult and aging rats with the use of
      immunohistochemical and histochemical techniques. Nitric oxide synthase
      immunoreactive neurons within the adrenal gland were found from the 20th day of
      gestation onwards. During early development the neurons were found as small
      clusters of smaller-size cells compared to those observed in the adult gland.
      Their number reached that of adult level by the 4th day after birth, and in the
      glands from aging rats a 28.6% increase was observed. Whilst no
      immunofluorescence was seen in chromaffin cells during early development, some
      cells from glands of aging rats showed nitric oxide synthase-immunoreactivity
      with varying intensity. The immunoreactive neurons from postnatal rat adrenals
      were also positive for NADPH-diaphorase, whilst those in prenatal rats were
      negative or lightly stained. Nitric oxide synthase-immunoreactive nerve fibres
      were present in all adrenal glands examined from the 16th day of gestation
      onwards. A considerable degree of variation in the distribution of immunoreactive
      fibres both in medulla and outer region of cortex at the different age groups was
      observed and described. Most, but not all, nitric oxide synthase-immunoreactive
      nerve fibres also showed NADPH-diaphorase staining.

PMID- 7514500
TI  - Localisation of substance P-like immunoreactivity in the ciliary ganglia of
      monkey (Macaca fascicularis) and cat: a light- and electron-microscopic study.
AB  - The present study describes substance P-like immunoreactivity in the ciliary
      ganglia of monkey (Macaca fascicularis) and cat. About 60% of neurons in the
      monkey ciliary ganglion and 40% in the cat ciliary ganglion were substance P-like
      immunoreactive, ranging from faint to moderate staining. Substance P-like
      immunoreactivity was located in cell bodies, dendritic profiles and axons. In the
      monkey, substance P-like immunoreactive pericellular arborisations were
      associated with about 0.5%-3% of the ganglion cells, which were either
      negatively, faintly or moderately stained. An electron-microscopic study
      demonstrated the presence of either substance P-like immunoreactive positive or
      negative axon terminals synapsing or closely associated with positive dendritic
      profiles in both the monkey and cat ciliary ganglia. The results suggest that
      substance P plays an important role in the ciliary ganglion, perhaps as a
      modulator or transmitter.

PMID- 7514501
TI  - Coexistence of substance P, neuropeptide Y, VIP, and CGRP in the nerve fibers of
      the carotid labyrinth of the bullfrog, Rana catesbeiana: a double-labelling
      immunofluorescence study in combination with alternate consecutive sections.
AB  - Double immunohistochemical staining with rhodamine- and fluorescein
      isothiocyanate (FITC)-conjugated antisera revealed the coexistence of substance P
      (SP) and neuropeptide Y (NPY), and SP and calcitonin gene-related peptide (CGRP)
      in most nerve fibers in the intervascular stroma of the carotid labyrinth of the
      bullfrog, Rana catesbeiana, although there were a few fibers which showed only SP
      or NPY-immunoreactivity. Approximately one third of SP-immunoreactive fibers
      also showed coexistence with vasoactive intestinal polypeptide (VIP)
      immunoreactivity, and a few fibers contained VIP without SP. The combination of
      the double immunofluorescence technique and alternate consecutive sections
      further demonstrated the possible coexistence of SP, VIP, NPY, and CGRP. This
      coexistence of four different peptides in the same nerve fibers was proved by the
      following two evident facts: 1) some SP fibers which demonstrated coexistence
      with NPY-immunoreactivity were assumed to be continuous with those showing VIP
      immunoreactivity, and 2) almost all of the SP fibers showed coexistence with CGRP
      immunoreactivity. By this reasoning, nearly one third of SP fibers may
      demonstrate coexistence with NPY-, VIP-, and CGRP-immunoreactivities. These
      multiple peptides might be involved in vascular regulatory function, which is a
      possible function of the amphibian carotid labyrinth.

PMID- 7514502
TI  - Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and
      loss of limb proprioceptive afferents.
AB  - Neurotrophin-3-deficient (NT-3-deficient) mice were generated by gene targeting.
      Mutant mice displayed severe movement defects of the limbs, and most died shortly
      after birth. Substantial portions of peripheral sensory and sympathetic neurons
      were lost while motor neurons were not affected. Significantly, spinal
      proprioceptive afferents and their peripheral sense organs (muscle spindles and
      Golgi tendon organs) were completely absent in homozygous mutant mice. This
      correlated with a loss of parvalbumin and carbonic anhydrase-positive neurons in
      the dorsal root ganglion. No gross abnormalities were seen in Pacinian
      corpuscles, cutaneous afferents containing substance P and calcitonin gene
      related peptide, and deep nerve fibers in the joint capsule and tendon.
      Importantly, the number of muscle spindles in heterozygous mutant mice was half
      of that in control mice, indicating that NT-3 is present at limiting
      concentrations in the embryo.

PMID- 7514503
TI  - Stabilization of calcium release channel (ryanodine receptor) function by FK506
      binding protein.
AB  - FK506-binding protein (FKBP12) was originally identified as the cytosolic
      receptor for the immunosuppressant drugs FK506 and rapamycin. The cellular
      function of FKBP12, a ubiquitously expressed 12,000-dalton proline isomerase, has
      been unknown. FKBP12 copurifies with the 565,000-dalton ryanodine receptor (RyR),
      four of which form intracellular Ca2+ release channels of the sarcoplasmic and
      endoplasmic reticula. By coexpressing the RyR and FKBP12 in insect cells, we have
      demonstrated that FKBP12 modulates channel gating by increasing channels with
      full conductance levels (by > 400%), decreasing open probability after caffeine
      activation (from 0.63 +/- 0.09 to 0.04 +/- 0.02), and increasing mean open time
      (from 4.4 +/- 0.6 ms to 75 +/- 41 ms). FK506 or rapamycin, inhibitors of FKBP12
      isomerase activity, reverse these stabilizing effects. These results provide the
      first natural cellular function for FKBP12, and establish that the functional
      Ca2+ release channel complex includes FKBP12.

PMID- 7514505
TI  - Lp(a): an acute-phase reactant?
AB  - The present study was designed to confirm the transient increases of plasma Lp(a)
      levels as an acute-phase reactant and to clarify the significance of these
      increases with the use of patients with acute myocardial infarction and patients
      subjected to surgical operations. Although interleukin 6, C-reactive protein and
      alpha 1 antitrypsin reached the maximal levels 1-2 days, 3 days and 4-5 days,
      respectively, after the episodes, the peak time of Lp(a) levels was delayed some
      extent in both patient groups. Studying the transient increases of Lp(a) levels
      as a function of apo(a) isoforms analyzed by density-gradient ultracentrifugation
      and SDS-PAGE, the higher-density Lp(a) particles preferentially containing high
      molecular-weight apo(a) isoforms increased more than the lower-density Lp(a)
      particles containing low-molecular-weight apo(a) after the episodes. The
      immunohistochemical findings suggest that Lp(a) may play an important role as an
      acute-phase reactant in the repair of tissue injury, especially in the process of
      angiogenesis.

PMID- 7514504
TI  - Odd Oz: a novel Drosophila pair rule gene.
AB  - We have identified a novel pair rule gene in Drosophila, odd Oz (odz). Every odd
      numbered body segment is deleted in odz mutant embryos. The odz gene product is
      strongly expressed in the embryonic central nervous system and heart, and both of
      these tissues are malformed in mutant embryos. Odz represents the only known pair
      rule gene that does not encode a transcription factor. Instead, it encodes a
      protein with EGF-like repeats homologous to those of the extracellular matrix
      protein tenascin. The protein is also a putative transmembrane tyrosine kinase
      substrate. On the basis of its structure, odz must act in a cellularized embryo.
      This is consistent with odz expression, whose temporal appearance is indicative
      of a very late-acting pair rule gene.

PMID- 7514507
TI  - Phaeochromocytoma presenting as acute hyperamylasaemia and multiple organ
      failure.
AB  - Phaeochromocytoma may present in many different ways. We report an unusual
      presentation of phaeochromocytoma in a man with hyperamylasaemia and multiple
      organ failure thought to be due to acute relapsing pancreatitis. Abdominal
      ultrasound and computerised tomography (CT) examinations revealed a mass at the
      tail of the pancreas. Fine needle biopsy of the mass precipitated headache,
      intense vasoconstriction and labile blood pressure. He proceeded to laparotomy,
      at which an 8 x 9 cm mass was found to be replacing the left adrenal gland.
      Histological examination revealed a phaeochromocytoma. This case illustrates that
      hyperamylasaemia and multiple organ failure may be unusual presentations of
      phaeochromocytoma and may be unusual presentations of phaeochromocytoma and
      phaeochromocytoma should be considered in the differential diagnosis of a
      peripancreatic mass found by ultrasound or CT.

PMID- 7514506
TI  - Hydromorphone patient-controlled analgesia (PCA) after coronary artery bypass
      surgery.
AB  - We conducted a study to compare the effectiveness of patient-controlled analgesia
      (PCA) technique to conventional analgesic therapy (CAT) after coronary artery
      bypass graft (CABG). The PCA group received hydromorphone 0.1 mg.hr-1 basal
      infusion and bolus doses of 0.2 mg Q 5 min (maximum 1.2 mg.hr-1) while the CAT
      group received morphine 2.5 mg iv Q 30 min prn until extubation followed by prn
      meperidine 1 mg.kg-1 im Q 4 hr or acetaminophen 325 mg with codeine 30 mg po (1
      or 2 tablets) when oral intake was possible. The degree of pain was assessed
      using a Visual Analogue Scale (VAS) starting after extubation and every 6-8 hr
      for the next 60 hr. Holter monitoring was initiated one hour after patient
      arrival in the Intensive Care Unit (ICU) and continued for 72 hr. Other measured
      variables were pulmonary function, sedation, side effects and total opioid
      requirements. Results show that the day-to-day VAS pain score decreased in the
      PCA group (P < 0.001) while it remained unchanged in CAT patients. The PCA
      patients had lower VAS pain scores at extubation (P < 0.05). During the third
      postoperative day, the PCA group had a lower VAS pain score, a lower incidence of
      severe pain defined as a score > 5 on the VAS scale, and a reduced incidence of
      myocardial ischaemia (P < 0.01). However, there was no difference in the
      duration, severity, area under the curve (AUC), or heart rate during ischaemic
      events. Postoperative pulmonary function was abnormal in both groups (NS) with
      minimal recovery by the fourth day.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514508
TI  - Human connexin43 gap junction channels. Regulation of unitary conductances by
      phosphorylation.
AB  - Connexin43 is the major gap protein in the heart and cardiovascular system.
      Single channel recordings of human connexin43 gap junction channels exogenously
      expressed in transfected SKHep1 cells demonstrate two discrete classes of channel
      events, with unitary conductances of predominantly 60 to 70 and 90 to 100 pS when
      recorded with an internal solution containing CsCl as the major current-carrying
      ionic species and at moderate transjunctional voltages (< 60 mV). Human
      connexin43 expressed in SKHep1 cells displays multiple electrophoretic mobilities
      (apparent M(r), approximately 41 to 45 kD) when resolved in Western blots.
      Treatment of connexin43 from these cells with alkaline phosphatase collapses the
      bands into a single 41-kD species; application of alkaline phosphatase to the
      cell interior through patch pipettes yields channels that are predominantly of
      the larger unitary conductance. The smaller 60- to 70-pS unitary conductance
      values correspond to the most common channel size seen in cultured rat cardiac
      myocytes; these channels were more frequently observed after treatment with the
      phosphatase inhibitor okadaic acid, which was shown to increase phosphorylation
      of human connexin43 in these cells under similar conditions. Exposure to the
      protein kinase inhibitor staurosporine shifted the proportion of events toward
      the largest unitary conductance and resulted in decreased phosphorylation of
      human connexin43 in seryl residues in these cells. Thus, the unitary conductance
      of human connexin43 gap junction channels covaries with the phosphorylation state
      of the protein. This change in unitary conductance appears to be a unique effect
      of phosphorylation on gap junction channels, since it has not been observed for
      other ion channels that have thus far been evaluated.

PMID- 7514510
TI  - A dynamic model of the cardiac ventricular action potential. II.
      Afterdepolarizations, triggered activity, and potentiation.
AB  - The action potential model presented in our accompanying article in this journal
      is used to investigate phenomena that involve dynamic changes of [Ca2+]i, as
      described below. Delayed afterdepolarizations (DADs) are induced by spontaneous
      Ca2+ release from the sarcoplasmic reticulum (SR), which, in turn, activates both
      the Na(+)-Ca2+ exchanger (INaCa) and a nonspecific Ca(2+)-activated current
      (Ins(Ca)). The relative contributions of INaCa and of Ins(Ca) to the generation
      of DADs are different under different degrees of Ca2+ overload. Early
      afterdepolarizations (EADs) can be categorized into two types: (1) plateau EADs,
      resulting from a secondary activation of the L-type Ca2+ current during the
      plateau of an action potential, and (2) phase-3 EADs, resulting from activation
      of INaCa and Ins(Ca) by increased [Ca2+]i due to spontaneous Ca2+ release from
      the SR during the late repolarization phase. Spontaneous rhythmic activity and
      triggered activity are caused by spontaneous Ca2+ release from the SR under
      conditions of Ca2+ overload. Postextrasystolic potentiation reflects the time
      delay associated with translocation of Ca2+ from network SR to junctional SR. The
      cell is paced at high frequencies to investigate the long-term effects on the
      intracellular ionic concentrations.

PMID- 7514509
TI  - A dynamic model of the cardiac ventricular action potential. I. Simulations of
      ionic currents and concentration changes.
AB  - A mathematical model of the cardiac ventricular action potential is presented. In
      our previous work, the membrane Na+ current and K+ currents were formulated. The
      present article focuses on processes that regulate intracellular Ca2+ and depend
      on its concentration. The model presented here for the mammalian ventricular
      action potential is based mostly on the guinea pig ventricular cell. However, it
      provides the framework for modeling other types of ventricular cells with
      appropriate modifications made to account for species differences. The following
      processes are formulated: Ca2+ current through the L-type channel (ICa), the
      Na(+)-Ca2+ exchanger, Ca2+ release and uptake by the sarcoplasmic reticulum (SR),
      buffering of Ca2+ in the SR and in the myoplasm, a Ca2+ pump in the sarcolemma,
      the Na(+)-K+ pump, and a nonspecific Ca(2+)-activated membrane current.
      Activation of ICa is an order of magnitude faster than in previous models.
      Inactivation of ICa depends on both the membrane voltage and [Ca2+]i. SR is
      divided into two subcompartments, a network SR (NSR) and a junctional SR (JSR).
      Functionally, Ca2+ enters the NSR and translocates to the JSR following a
      monoexponential function. Release of Ca2+ occurs at JSR and can be triggered by
      two different mechanisms, Ca(2+)-induced Ca2+ release and spontaneous release.
      The model provides the basis for the study of arrhythmogenic activity of the
      single myocyte including afterdepolarizations and triggered activity. It can
      simulate cellular responses under different degrees of Ca2+ overload. Such
      simulations are presented in our accompanying article in this issue of
      Circulation Research.

PMID- 7514511
TI  - Intracellular alkalinization induced by bradykinin sustains activation of the
      constitutive nitric oxide synthase in endothelial cells.
AB  - The transient increase in [Ca2+]i in endothelial cells after stimulation with
      bradykinin can account for the initiation but not the sustained production of
      nitric oxide (NO). Therefore, we investigated whether this sustained activation
      of the constitutive NO synthase (cNOS) could be mediated by an increase in pHi,
      which is induced by an activation of the Na(+)-H+ exchanger rather than an
      increase in [Ca2+]i. Cultured human endothelial cells grown on coverslips were
      loaded with either C.SNAFL-2 or fura 2-AM for fluorometric analysis of either pHi
      or [Ca2+]i. NO release was assayed by the ability of effluent from endothelial
      cells to stimulate purified soluble guanylyl cyclase. The pH dependence of a
      microsomal cNOS preparation was determined by assay of L-[3H]citrulline formation
      from L-[3H]arginine. Bradykinin (10 nmol/L) induced a biphasic change in
      endothelial pHi consisting of an initial acidification followed by a prolonged
      alkalinization above resting values. Inhibition of the Na(+)-H+ exchanger using
      HOE 694 (10 mumol/L) prevented this increase in pHi. The L-citrulline assay
      revealed a twofold increase in cNOS activity on increasing pH from 6.7 to 7.4, an
      optimum at pH 7.5, and a complete abolition of activity at pH 8.6. Endothelial
      production of NO 15 minutes after starting the infusion of bradykinin was
      maintained at significantly higher levels in control cells compared with cells
      pretreated with HOE 694. The latter effect cannot be accounted for by an increase
      in intracellular Ca2+, since [Ca2+]i levels were not significantly different
      between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514512
TI  - Prostate volume in testosterone-treated and untreated hypogonadal men in
      comparison to age-matched normal controls.
AB  - OBJECTIVE: The potential use of testosterone preparations for substitution
      therapy for ageing men and for male contraception, in addition to the well
      established substitution therapy of male hypogonadism, make increased
      testosterone use likely. However, little clinical information is available on the
      effect of testosterone therapy on the prostate in hypogonadal men. DESIGN AND
      MEASUREMENTS: In a controlled cross-sectional study, prostate volume measured by
      transrectal ultrasonography, serum levels of prostate-specific antigen (PSA) and
      sex hormones, and uroflow parameters were determined. PATIENTS: Three groups of
      age-matched men were enrolled in the study: 47 newly diagnosed hypogonadal men
      before testosterone treatment, 78 hypogonadal men with at least 6 months of
      effective testosterone therapy and 75 normal men. RESULTS: Regression analysis
      revealed a significant positive correlation of prostate volume with age in normal
      men and testosterone-treated hypogonadal men, whereas no significant correlation
      was detected in untreated hypogonadal men. Prostate volume was significantly
      lower in untreated hypogonadal men (12.2 (11.0-13.5) ml) (mean (95% confidence
      limits)) compared to both other groups. However, no significant difference in
      prostate volume was detected between testosterone-treated hypogonadal men (21.3
      (19.9-22.8) ml) and normal men (22.9 (21.4-24.4) ml). Similar results were
      obtained for PSA with comparable values in the testosterone-treated hypogonadal
      men (0.98 (0.88-1.10) micrograms/l) and normal men (1.02(0.91-1.14)
      micrograms/l), and significantly lower concentrations in the untreated
      hypogonadal men (0.64 (0.55-0.73) micrograms/l). No differences in uroflow
      parameters were detected between the three study groups. CONCLUSIONS: Effective
      testosterone treatment of hypogonadal men results in prostate volume and prostate
      specific antigen levels comparable to age-matched normal men. Therefore,
      testosterone-induced prostate growth should not preclude hypogonadal men from
      testosterone substitution therapy.

PMID- 7514513
TI  - Pharmacokinetics and metabolic effects of growth hormone injected subcutaneously
      in growth hormone deficient patients: thigh versus abdomen.
AB  - OBJECTIVE: The absorption of insulin following subcutaneous (s.c.) injection is
      faster in the abdomen than the thigh. We therefore studied the effect of changing
      the site of injection on the absorption and metabolic effects of human growth
      hormone. DESIGN AND MEASUREMENTS: In a cross-over study human GH (Norditropin)
      was injected s.c. in the thigh or abdomen in random order. Ultrasonography of the
      thigh and abdomen was performed in order to evaluate the thickness of the s.c.
      tissue. After each treatment period (4 weeks), serum profiles of GH, IGF-I, IGF
      binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), glucose, insulin, non-esterified
      fatty acids (NEFA), glycerol, 3-hydroxybutyrate, alanine, lactate and glucagon
      were measured for 37 hours after GH injection (3 IU/m2 at 1900 hour). PATIENTS:
      Nine GH deficient patients (five males, four females). RESULTS: The mean (+/-
      SEM) thickness of the s.c. tissue (mm) was higher on the abdominal site (9.35 +/-
      1.38 (thigh), and 22.61 +/- 2.19 (abdomen), P < 0.001). Mean (+/- SEM) integrated
      levels (area under the curves (AUC) divided by time) of GH (mU/l) were identical:
      5.54 +/- 0.70 (thigh) versus 5.48 +/- 0.64 (abdomen) (P = 0.91). AUC (mU/l) for
      the initial 6 hours were, however, significantly different (14.10 +/- 3.76
      (thigh) and 19.02 +/- 3.18 (abdomen), P = 0.02). Maximal serum concentration
      (Cmax) (mU/l) 23.18 +/- 3.86 (thigh) and 29.66 +/- 4.78 (abdomen) (P = 0.19) was
      achieved faster (Tmax) following injection in the abdomen. Tmax (hours) was 5.89
      +/- 0.41 (thigh) and 4.26 +/- 0.49 (abdomen) (P < 0.002). Mean IGF-I levels
      (microgram/l) were unaffected by GH injection sites (355 +/- 60 (thigh) and 365
      +/- 63 (abdomen), P = 0.61). Mean IGFBP-3 levels (microgram/l) were significantly
      different (2100 +/- 143 (thigh), and 2350 +/- 176 (abdomen), P = 0.05). Mean
      levels of IGFBP-1, insulin, glucose, lipid intermediates, metabolites and
      glucagon were not significantly different. CONCLUSIONS: Human GH was absorbed
      faster when injected s.c. in the abdomen as compared with the thigh, despite the
      thicker s.c. tissue on the abdomen. Apart from higher IGFBP-3 levels after s.c.
      injections in the abdomen, similar metabolic effects of GH were obtained with the
      two injection sites.

PMID- 7514514
TI  - Gynaecomastia caused by a primary mediastinal seminoma.
AB  - The case of a young man aged 26 is reported. He presented with a short history of
      painful gynaecomastia, and no other associated symptoms. Radiological
      investigations showed a mass in the anterior mediastinum. Endocrine
      investigations showed high circulating oestradiol and high hCG-beta levels. There
      was no evidence of primary testicular tumour or metastases. Surgical removal of
      the mediastinal mass led to normalization of oestradiol and hCG-beta levels and
      regression of gynaecomastia. Histology showed the tumour to be a primary
      mediastinal seminoma staining positively for hCG-beta. Further treatment
      consisted of chemotherapy with etoposide and cis-platinum. The patient has
      remained well with no evidence of disease recurrence. The tumour markers remain
      normal.

PMID- 7514516
TI  - Circulating adhesion molecules in sarcoidosis.
AB  - Sarcoidosis is a disease of unknown etiology characterized by non-caseating
      granulomata together with a number of systemic abnormalities. We have recently
      shown these include increased expression of the integrins CD11/CD18 on peripheral
      blood leucocytes. Here we have measured serum levels of the adhesion molecules
      intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion
      molecule-1 (VCAM-1) in 23 patients and 14 normal controls using antigen capture
      sandwich ELISAs. Median circulating E-selectin levels in the patients were nearly
      three times those of the controls (P < 0.0001, Mann-Whitney U-test), whilst ICAM
      1 but not VCAM-1 levels were only slightly elevated. These results show that
      endothelial cell activation and shedding of E-selectin into the circulation are
      additional features of the pathology of sarcoidosis.

PMID- 7514515
TI  - Identification of antibody epitopes in the CB-11 peptide of bovine type II
      collagen recognized by sera from arthritis-susceptible and -resistant rhesus
      monkeys.
AB  - Sera from eight rhesus monkeys that had been immunized with native bovine type II
      collagen were tested for antibodies to cyanogen bromide peptides (CB peptides) of
      type II collagen by Western blotting. The monkeys produced IgG antibodies to a
      number of different CB peptides, with five out of eight animals producing
      antibodies to the CB-11 peptide (four arthritic, one non-arthritic). Antibody
      epitopes on the CB-11 peptide of bovine type II collagen recognized by these sera
      were investigated by epitope mapping. Peptides (8-mers overlapping by seven amino
      acids) representing the CB-11 region were synthesised and the sera screened for
      binding to these peptides to determine areas of high IgG antibody binding to this
      region of type II collagen. The profiles obtained were not identical, though
      there were some epitopes that were commonly recognized. Antibodies to one
      epitope, also present in human type II collagen, were found only in the sera of
      two animals with the severest arthritis. The technique of epitope mapping has
      successfully identified a number of epitopes within the CB-11 peptide of type II
      collagen recognized by antibodies from bovine type II collagen-immunized monkeys.
      Studies on the relevance of responses to the identified epitopes can now be
      undertaken.

PMID- 7514518
TI  - Homeotic gene expression in the locust Schistocerca: an antibody that detects
      conserved epitopes in Ultrabithorax and abdominal-A proteins.
AB  - To investigate what role homeotic genes may play in morphological evolution, we
      are comparing homeotic gene expression in two very different insects, Drosophila
      (Diptera) and Schistocerca (Orthoptera). In this paper we describe a monoclonal
      antibody, FP6.87, that recognizes the products of both the Ultrabithorax (Ubx)
      and abdominal-A (abd-A) genes in Drosophila, via an epitope common to the carboxy
      terminal region of these two proteins. This antibody recognizes nuclear antigens
      present in the posterior thorax and abdomen of Schistocerca. We infer that it
      recognizes the Schistocerca homolog of UBX protein, and probably also of ABD-A.
      As the distribution of Schistocerca ABD-A protein is already known, we can use
      this reagent to map the expression of Schistocerca UBX in the thorax and anterior
      abdomen, where ABD-A is not expressed. Both the general domain, and many of the
      details, of UBX expression are remarkably conserved compared with Drosophila.
      Thus UBX expression extends back from T2 in the ectoderm (including the CNS), but
      only from A1 in the mesoderm. As noted for other bithorax complex genes in
      Schistocerca, expression begins in the abdomen, at or shortly before the time of
      segmentation. It only later spreads anteriorly to the thorax. For much of
      embryogenesis, the expression of UBX in the thoracic epidermis is largely
      restricted to the T3 limb. In this limb, UBX is strikingly regulated, in a
      complex pattern that reflects limb segmentation. Reviewing these and earlier
      observations, we conclude that evolutionary changes affect both the precise
      regulation of homeotic genes within segments, and probably also the spectrum of
      downstream genes that respond to homeotic gene expression in a given tissue.
      Overall domains of homeotic gene expression appear to be well conserved between
      different insect groups, though a change in the extent and timing of homeotic
      gene expression may underlie the modification of the posterior abdomen in
      different insect groups.

PMID- 7514517
TI  - Modulation of immune response to Lol p I by pretreatment with anti-idiotypic
      antibody is not restricted to the idiotypic expression.
AB  - To study the role of anti-idiotypic antibodies in the regulation of the immune
      response to Lol p I (the major allergenic component of rye grass pollen), we have
      recently generated a panel of three MoAbs directed against distinct epitopes of
      Lolp I and an anti-idiotypic MoAb directed against the idiotype borne by one of
      the anti-Lol p I MoAbs (290A-167). The effects of pretreatment with this anti
      idiotypic MoAb in BALB/c mice before immunization with the antigen have been
      examined. The anti-idiotypic MoAb or unrelated MoAb were given weekly for 8 weeks
      intraperitoneally. Mice then received the antigen (2 micrograms) adsorbed with
      alum (2 mg) at weeks 9, 11 and 13. Serum anti-Lol p I antibodies (IgG or IgE) and
      specific idiotypic responses were measured. Anti-Lol p I IgG antibodies could be
      detected before immunization with Lol p I only in mice pretreated with anti
      idiotypic MoAb. Immunization with Lol p I induced an anti-Lol p I IgG response in
      both groups, but this response was higher in mice that received anti-idiotypic
      MoAb. Similar profiles were seen for specific IgE antibodies and idiotypic
      responses. Surprisingly, idiotypes borne by other anti-Lol p I MoAbs (539A-6 and
      348A-6) had also been enhanced after pretreatment with the anti-290A-167 MoAb.
      These observations suggested that the pretreatment with this anti-idiotypic MoAb
      modulates not only the expression of the respective idiotype, but also affects
      other idiotype responses.

PMID- 7514519
TI  - Acute systemic vanadate poisoning presenting as cerebrovascular ischemia with
      prolonged reversible neurological deficits (PRIND).
AB  - A 22-year-old woman is reported who attempted suicide by oral ingestion of
      approximately 10-15 g ammonium metavanadate (NH4VO3). A few hours later she
      developed gastrointestinal symptoms followed by a transient right sensomotor
      hemiparesis and aphasic disturbances. Brain MRI and SPECT with 99mTc-HMPAO
      revealed a lesion in the left parietal cortex. Plasmapheresis, ascorbic acid and
      desferoxamine led to a complete clinical recovery within a few days.

PMID- 7514521
TI  - Automated image cytometry for detection of rare, viral antigen-positive cells in
      peripheral blood.
AB  - A cell detection method based upon automated screening is described for
      recognition of low frequencies (1 in 100,000) of immuno-enzymatically labelled
      white blood cells in human peripheral blood. The used image cytometry
      instrumentation (LEYTAS) includes a wide-field, fully automated microscope
      (Autoplan) and a modular image analysis computer (MIAC), both from Leica,
      Wetzlar, Germany. The MIAC contains image boards for optimum use of mathematical
      morphology algorithms. Communication with the MIAC is via a personal computer.
      Programs for automated cell analysis have been written in C language. Main
      features of the system are fast analysis of large microscope fields including a
      count of all cells, selection of objects of interest (alarms), and display of
      digitally stored images of these alarms. We tested this system for the detection
      of white blood cells expressing antigen of cytomegalovirus (pp65) in 50 human
      blood smears from kidney transplant recipients. Immuno-enzymatic (peroxidase)
      staining was performed with DAB and counterstaining with hematoxylin. For
      determination of the sensitivity, a series of dilutions of a positive sample with
      a negative sample was performed. The lowest frequency detected was 1 antigen
      positive cell/3 x 10(5) antigen-negative cells. Screening time was about 60 min
      for one million cells.

PMID- 7514522
TI  - Further flow cytometric studies of the effects of triethylenemelamine on somatic
      and testicular tissues of the rat.
AB  - Exposure to the mutagen triethylenemelamine on rat bone marrow, blood, and testis
      was studied using flow cytometry of DAPI-stained nuclei. Increased coefficients
      of variation (CVs) of the G1 peaks were observed in bone marrow and blood after
      both 1 d and 5 d exposures. After 5 d exposure and 7 d recovery both tissues had
      recovered, in some cases to significantly lower CVs. Increased CVs of the 1C peak
      of testis were observed only after 5 d exposure to the high dose with no
      subsequently observed recovery. Bone marrow cells also were stained with Hoechst
      33258 and Propidium Iodide. No differences among dyes were observed indicating
      that increased CVs likely are due to DNA damage resulting from interactions with
      the mutagen rather than differences in how the dyes bind to DNA relative to
      mutagen binding. This study demonstrates that differences occur among tissues in
      how quickly they respond and recover from mutagen exposure. Increased CVs, cell
      cycle alterations, and decreased CVs after recovery are all potentially useful
      biomarkers of effect for laboratory and field studies in environmental
      toxicology.

PMID- 7514520
TI  - Dansyl chloride labelling of stratum corneum: its rapid extraction from skin can
      predict skin irritation due to surfactants and cleansing products.
AB  - The irritation potential of surfactants and body cleansing products was
      determined by evaluating the removal of dansyl chloride from the skin. Dilute
      solutions (2% active ingredient, w/v) of surfactants and soap extract
      fluorescence from the skin within 30 min. This is probably a physicochemical
      effect as it is too rapid to be due to a modification of epidermal cell turnover
      rate. Such an extraction of the fluorescent dye occurs without any clinical sign
      of irritation. However, it may represent an early phase of the skin irritation
      process, because it is related to the ranking of irritant products as determined
      by other assessment methods.

PMID- 7514523
TI  - Lymphocyte subset analysis by Boolean algebra: a phenotypic approach using a
      cocktail of 5 antibodies and 3 color immunofluorescence.
AB  - Commercial reagent kits for the evaluation of leukocyte subsets involve the
      staining of a panel of up to six tubes using combinations of pre-mixed
      fluorescein isothiocyanate (FITC) and R-phycoerythrin (PE) conjugated monoclonal
      antibodies. We describe a rapid method whereby total CD3+ T-cells, CD4+ T-cells
      (CD3+ CD4+), CD8+ T-cells (CD3+ CD8+), putative gamma delta-receptor-T-cells
      (CD3+ CD4- CD8-), and T-cells that are CD3+ CD4+ CD8+ as well as B-lymphocytes
      and NK-cells can be enumerated after staining in a single tube. Whole blood
      specimens are labelled with a mixture of antibodies: FITC-conjugated antibodies
      to CD4 and CD19, PE-conjugated antibodies to CD8 and CD16, and either peridinin
      chlorophyll protein (PerCP) or allophycocyanin (APC) labelling for antibodies to
      CD3. After recording 20,000 events the data were analysed on the Consort 32
      computer system and LYSYS-II (Becton Dickinson, San Jose, CA) and all of the
      lymphocyte subset values were determined by Boolean algebra using a technique we
      refer to as Boolean gate analysis (BGA). Our study has shown that BGA is
      statistically equivalent to SimulSET lymphocyte subset analysis. Furthermore, the
      procedure reduces the number of tubes required to two with consequential saving
      in reagents, consumables, and time.

PMID- 7514525
TI  - X chromosome retains the memory of its parental origin in murine embryonic stem
      cells.
AB  - A cytogenetic and biochemical study of balloon-like cystic embryoid bodies,
      formed by newly established embryonic stem (ES) cell lines having a
      cytogenetically or genetically marked X chromosome, revealed that the paternally
      derived X chromosome was inactivated in the majority of cells in the yolk sac
      like mural region consisting of the visceral endoderm and mesoderm. The
      nonrandomness was less evident in the more solid polar region containing the
      ectodermal vesicle, mesoderm and visceral endoderm. Since the same was true in
      embryoid bodies derived from ES cells at the 30th subculture generation, it was
      concluded that the imprinting responsible for the preferential inactivation of
      the paternal X chromosome that was limited to non-epiblast cells of the female
      mouse embryos, was stably maintained in undifferentiated ES cells.
      Differentiating epiblast cells should be able to erase or avoid responding to the
      imprint.

PMID- 7514524
TI  - Multiple labeling using two-color immunofluorescence with only one light source,
      two fluorescence photomultiplier tubes, and two light scatter detectors.
AB  - Multiple labeling is necessary for the detailed phenotyping of cells in many
      biological systems in human and animal species. In a previous report, we
      described an approach permitting the study of three labels simultaneously by
      using the two-color immunofluorescence and one light source (Mansour et al.,
      Cytometry 11:636-641, 1990). This approach allowed enumeration of cell
      subpopulations positive for only one label and negative for many others (X+ A- B-
      ...). We here present an improvement of the previous approach to allow analysis
      of double positive phenotypes (X+ Y+ A- B- ...), using only two fluorescence
      photomultiplier tubes and light scatter detectors. It consists of a two-step
      analysis that does not require additional material than that used in the former
      technique. Briefly, all antibodies are conjugated to only two fluorochromes:
      either FITC or PE. For the analysis of the X+ Y+ A- B- ... phenotype, the Y, A
      and B labels are all coupled to the same dye (FITC, e.g.) and the X label to the
      other dye (i.e, PE). In a first step, cells are labeled with X, A, and B, and in
      a second step, the second positive (Y) label is added. Two examples are supplied:
      CD56+ CD2+ CD3- CD16- decidua infiltrating cells and CD3+ TCR delta+ CD4- CD8-
      peripheral blood lymphocytes. This technique is useful for qualitative as well as
      quantitative analysis, with cytometers that do not have the appropriate hardware
      to do true three-color immunofluorescence analysis.

PMID- 7514527
TI  - Current observations on sickle cell genotype in Nigeria.
AB  - The haematological indices and clinical manifestations of sickle cell disease
      (SCD) patients were investigated in a combined group of male and female
      Nigerians, and the results were matched against those from non-SCD individuals.
      Haemoglobin concentrations (Hb), red blood cell count (RBC) and packed cell
      volume (PCV) were significantly lower in the haemoglobin SS (HbSS) individuals
      than in the haemoglobin AS (HbAS) and haemoglobin AA (HbAA) individuals. White
      cell count (WBC) was of course higher in the HbSS patients as was the foetal
      haemoglobin (HbF) also. The clinical investigations show a 16% incidence of leg
      ulceration amongst the SCD patients and a 25% incidence of 'crisis state'
      requiring blood transfusion. Comparison of these findings with those obtained for
      Jamaicans and Saudi Arabian sickle cell patients show several differences
      indicating a milder disease in the Nigerian than the Jamaicans.

PMID- 7514526
TI  - Expression of the protein zero myelin gene in axon-related Schwann cells is
      linked to basal lamina formation.
AB  - A Schwann cell has the potential to differentiate into either a myelinating or
      ensheathing cell depending upon signals received from the axon that it contacts.
      Studies focusing on the pathway leading to myelination demonstrated that Schwann
      cells must form a basal lamina in order to myelinate an axon. In this report, we
      describe studies that indicate that initiation of basal lamina synthesis is
      required for Schwann cells to distinguish between myelination-inducing axons and
      axons that do not induce myelination, and to respond by undergoing the
      appropriate genetic and cellular changes. We have used high resolution in situ
      hybridization, immunocytochemistry and electron microscopy to examine changes in
      gene expression and morphology of Schwann cells differentiating into myelin
      forming cells in vitro. These experiments were carried out in dorsal root
      ganglion neuron/Schwann cell co-cultures maintained in either serum-free, serum
      only or serum-plus-ascorbate-containing medium. We have made four novel
      observations that contribute significantly to our understanding of how basal
      lamina and myelination are linked. (1) The addition of ascorbate (in the presence
      of serum), which promotes basal lamina production, appears to induce expression
      of the protein zero gene encoding the major structural protein of myelin.
      Moreover, expression of protein zero mRNA and protein, and its insertion into
      myelin membranes, occurs only in the subset of Schwann cells contacting
      myelination-inducing axons. Schwann cells in contact with axons that do not
      induce myelination, or Schwann cells that have not established a unitary
      relationship with an axon, do not express protein zero mRNA although they produce
      basal lamina components. (2) In serum-free conditions, a majority of Schwann
      cells express protein zero mRNA and protein, but this change in gene expression
      is not associated with basal lamina formation or with elongation of the Schwann
      cell along the axon and elaboration of myelin. (3) In the presence of serum (and
      the absence of ascorbate), Schwann cells again fail to form basal lamina or
      elongate but no longer express protein zero mRNA or protein. (4) Myelin
      associated glycoprotein and galactocerebroside, two additional myelin-specific
      components, can be expressed by Schwann cells under any of the three culture
      conditions. Therefore, we have demonstrated that axonal induction of protein zero
      gene expression in Schwann cells is subject to regulation by both serum- and
      ascorbate-dependent pathways and that not all myelin-specific proteins are
      regulated in the same manner.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514528
TI  - Dynamics of prolactin in amniotic fluid and extraembryonic coelomic fluid in
      early human pregnancy.
AB  - Concentrations of prolactin were measured by an immunoradiometric assay in 26
      matched samples of amniotic fluid, extraembryonic coelomic fluid and maternal
      serum from 9 to 12 weeks of pregnancy and in a further 131 amniotic fluid samples
      from 9 to 20 weeks. Low levels of prolactin (median 40 MU/l) were present in
      amniotic fluid from 9 to 12 weeks. Levels in the coelomic fluid were higher
      (median level 371 MU/l; P < 0.0001) than in amniotic fluid. From 13 weeks, there
      was a rapid rise in amniotic fluid prolactin to reach a peak at 19 weeks (median
      level 99,850 MU/l). The pattern of increase of prolactin in amniotic fluid is
      similar to, but occurs 2 weeks later than that for insulin-like growth factor
      binding protein-1, another major decidual product.

PMID- 7514529
TI  - Cyclic ADP-ribose regulation of ryanodine receptors involved in agonist evoked
      cytosolic Ca2+ oscillations in pancreatic acinar cells.
AB  - We have investigated the role of the ryanodine-sensitive intracellular Ca2+
      release channel (ryanodine receptor) in the cytosolic Ca2+ oscillations evoked in
      pancreatic acinar cells by acetylcholine (ACh) or cholecystokinin (CCK).
      Ryanodine abolished or markedly inhibited the agonist evoked Ca2+ spiking, but
      enhanced the frequency of spikes evoked by direct internal inositol trisphosphate
      (InsP3) application. We have also investigated the possibility that cyclic ADP
      ribose (cADP-ribose), the putative second messenger controlling the ryanodine
      receptor, plays a role in Ca2+ oscillations. We found that cADP-ribose could
      itself induce repetitive Ca2+ spikes localized in the secretory pole and that
      these spikes were blocked by ryanodine, but also by the InsP3 receptor antagonist
      heparin. Our results indicate that both the ryanodine and the InsP3 receptors are
      involved in Ca2+ spike generation.

PMID- 7514530
TI  - Reverse transcriptase activity of an intron encoded polypeptide.
AB  - A number of group II introns from eukaryotic organelles and prokaryotes contain
      open reading frames for polypeptides with homology to retroviral reverse
      transcriptases (RTs). We have used the yeast transposon (Ty) system to express
      ORFs for RTs from eukaryotic organelles. This includes the mitochondrial coxI
      intron i1 from the fungus Podospora anserina, the plastid petD intron from the
      alga Scenedesmus obliquus and the mitochondrial RTL gene from the alga
      Chlamydomonas reinhardtii. The ORFs were fused with the TYA ORF from the yeast
      retrotransposon Ty to produce virus-like particles in the recipient strains with
      detectable amounts of the RT-like polypeptides. Analysis of the heterologous gene
      products revealed biochemical evidence that the P. anserina intron encodes an RNA
      directed DNA polymerase with properties typically found for RTs of viral or
      retrotransposable origin. In vitro assays showed that the intron encoded RT is
      sensitive to RT inhibitors such as N-ethylmaleimide and dideoxythymidine
      triphosphate but is insensitive against the DNA polymerase inhibitor aphidicolin.
      The direct biochemical evidence provided here supports the idea that intron
      encoded RTs are involved in intron transposition events.

PMID- 7514532
TI  - A novel RNA gene in the tobacco plastid genome: its possible role in the
      maturation of 16S rRNA.
AB  - A small plastid-encoded RNA (spRNA, 218 nt) has been detected in tobacco. The
      corresponding locus (sprA) does not contain any open reading frame and is
      actively transcribed from its own promoter, as shown by ribonuclease protection
      assays using in vitro capped RNAs. Gel-shift and UV-crosslinking experiments
      showed the formation of a specific complex between spRNA and chloroplast
      polypeptides. The mobility of the complex was further shifted when a transcript
      bearing part of the 16S rRNA leader sequence was added to the incubation mixture.
      Glycerol gradient fractionation of a chloroplast lysate indicated a preferential
      sedimentation of spRNA at 15-20S and 70S. These observations, and the potential
      base-pairing with the leader sequence of pre-16S rRNA, suggest a role for spRNA
      in chloroplast ribosome biogenesis, i.e. 16S rRNA maturation. By sequencing of
      tomato plastid DNA and heterologous northern hybridizations, the presence of sprA
      homologs and their expression in a number of dicot plants have also been shown.

PMID- 7514531
TI  - Mammary gland factor (MGF) is a novel member of the cytokine regulated
      transcription factor gene family and confers the prolactin response.
AB  - Milk protein gene expression in mammary epithelial cells is regulated by the
      action of the lactogenic hormones insulin, glucocorticoids and prolactin. The
      mammary gland factor, MGF, has been shown to be a central mediator in the
      lactogenic hormone response. The DNA binding activity of MGF is hormonally
      regulated and essential for beta-casein promoter activity. We have used Red A
      Sepharose- and sequence-specific DNA affinity chromatography to purify MGF from
      mammary gland tissue of lactating sheep. Proteins of 84 and 92 kDa were obtained,
      proteolytically digested and the resulting peptides separated by reverse phase
      high pressure liquid chromatography. The 84 and 92 kDa proteins yielded very
      similar peptide patterns. The amino acid sequence of two peptides was determined.
      The sequence information was used to derive oligonucleotide probes. A cDNA
      library from the mRNA of mammary gland tissue of lactating sheep was screened and
      a molecular clone encoding MGF was isolated. MGF consists of 734 amino acids and
      has sequence homology with the 113 (Stat113) and 91 kDa (Stat91) components of
      ISGF3, transcription factors which are signal transducers of IFN-alpha/beta and
      IFN-gamma. Two species of MGF mRNA of 6.5 and 4.5 kb were detected in mammary
      gland tissue of lactating sheep. Lower mRNA expression was found in ovary,
      thymus, spleen, kidney, lung, muscle and the adrenal gland. MGF cDNA was
      incorporated into a eukaryotic expression vector and cotransfected with a vector
      encoding the long form of the prolactin receptor into COS cells. A strong MGF
      specific bandshift was obtained with nuclear extracts of COS cells induced with
      prolactin. Treatment of activated MGF with a tyrosine-specific protein
      phosphatase resulted in the loss of DNA binding activity. Prolactin-dependent
      transactivation of a beta-casein promoter-luciferase reporter gene construct was
      observed in transfected cells.

PMID- 7514533
TI  - A general strategy to identify mimotopes of pathological antigens using only
      random peptide libraries and human sera.
AB  - A strategy to identify disease-specific epitopes from phage-displayed random
      peptide libraries using human sera is described. Peptides on phage (phagotopes)
      that react with antibodies present in patient sera are purified from > 10(7)
      different sequences by affinity selection and immunological screening of plaques.
      Disease-specific phagotopes can be identified out of this pool through an
      'antigen independent' procedure which avails itself only of patient and normal
      human sera. Using this strategy, we have selected antigenic mimics (mimotopes) of
      two different epitopes from the human hepatitis B virus envelope protein (HBsAg).
      We could show that a humoral response to these mimotopes is widespread in the
      immunized population, suggesting that the strategy identifies phagotopes that
      have a potential role as diagnostic reagents. Immunization of mice with the
      selected phagotopes elicited a strong specific response against the HBsAg. These
      results open new inroads into disease-related epitope discovery and provide the
      potential for vaccine development without a requirement for the use of, or even
      information about, the aetiological agent or its antigens.

PMID- 7514534
TI  - Sequence and expression of murine type I hair keratins mHa2 and mHa3.
AB  - A cDNA library was constructed with poly(A)+ RNA from mouse tail epidermis which
      contained all hair follicles of tail skin. The library was subjected to
      sequential screening procedures aimed at selecting cDNA clones coding for acidic,
      type I hair keratins. Two clones, pktI-2 and pktI-3, encoded keratins that could
      be identified as murine type I hair keratins mHa2 and mHa3, respectively, by
      positive hybridization selection analysis. Sequence comparisons with the known
      murine type I hair keratins mHa1 (Bertolino et al., J. Invest. Dermatol. 91, 541
      546, 1988) and mHa4 (Bertolino et al., J. Invest. Dermatol. 94, 297-303, 1990)
      revealed a structural heterogeneity within the type I hair keratin subfamily.
      Three keratins, mHa1, mHa3, and mHa4, are highly related, differing mainly in the
      penultimate part of their amino and carboxy termini. In contrast, mHa2 is
      structurally distinct from the three other keratins in both the alpha-helix and,
      in particular, the non-alpha-helical domains. These findings are confirmed by
      evolutionary investigations and flexibility calculations which indicate a more
      flexible nature of the mHa2 amino terminus when compared to the corresponding
      region of the three other keratins. In situ hybridization experiments with
      specific 3' fragments of mHa2 and mHa3 show that mHa3 is expressed in cortex
      cells, whereas mHa2 transcripts are strictly limited to the cuticle of the hair
      shaft. mHa3 mRNA expression can also be demonstrated in the central unit of the
      murine lingual filiform papillae, whereas the cuticular keratin mHa2 is not
      expressed in this body site. These data indicate that the structural
      heterogeneity within the type I hair keratin subfamily is functionally relevant
      in the morphogenesis of hard alpha-keratin-expressing tissues.

PMID- 7514535
TI  - Methylxanthines and calcium-mobilizing agents inhibit the expression of cytokine
      inducible nitric oxide synthase and vascular cell adhesion molecule-1 in murine
      microvascular endothelial cells.
AB  - In response to exposure to the inflammatory cytokines tumor necrosis factor-alpha
      (TNF) and interferon-gamma (IFN-gamma), murine brain microvascular endothelial
      cells (MME) synthesize the cell surface molecule, vascular cell adhesion molecule
      1 (VCAM-1), and the intracellular enzyme, inducible nitric oxide synthase (iNOS).
      However, iNOS synthesis requires the presence of both TNF and IFN-gamma, while
      VCAM-1 can be induced by either cytokine alone. We examined the induction of VCAM
      1 and iNOS under a variety of conditions to better define the regulation of TNF
      and IFN-gamma signal transduction pathways in MME. We utilized the analysis of
      steady-state levels of iNOS mRNA as well as the measurement of MME-released NO
      EDRF (nitric oxide as an endothelium-derived relaxing factor) activity and
      accumulation of nitrite in the culture medium to define iNOS expression and
      activity. VCAM-1 expression was determined by flow cytometric analysis. Our data
      indicate that low density lipoproteins inhibited cytokine-induced iNOS activity
      by affecting the steady-state levels of iNOS mRNA. Methylxanthines (caffeine and
      theophylline) as well as several calcium-mobilizing agents inhibited the
      expression/activity of both iNOS and VCAM-1 in MME. The effectiveness of these
      agents was dependent upon the degree of disruption in cell calcium homeostasis
      during cytokine treatment. Cells which had been pretreated with calcium
      modulating drugs and then washed and allowed to return to normal calcium
      homeostasis showed little to no effect from these agents. In addition, our
      results suggest that NO produced by iNOS acts as a metabolic switch during
      inflammation by inhibiting oxidative phosphorylation and forcing vascular
      endothelial cells to temporarily utilize anaerobic energy metabolism.

PMID- 7514536
TI  - Inhibition of nuclear protein import by a monoclonal antibody against a novel
      class of nuclear pore proteins.
AB  - Nuclear import of proteins is mediated by the nuclear pore complexes in the
      nuclear envelope and requires the presence of a nuclear localization signal (NLS)
      on the karyophilic protein. In this paper, we describe studies with a monoclonal
      antibody, Mab E2, which recognizes a class of nuclear pore proteins of 60-76 kDa
      with a common phosphorylated epitope on rat nuclear envelopes. The Mab E2
      reactive proteins fractionated with the relatively insoluble pore complex
      containing component of the envelope and gave a finely punctate pattern of
      nuclear staining in immunofluorescence assays. The antibody did not bind to any
      cytosolic proteins. Mab E2 inhibited the interaction of a simian virus 40 large T
      antigen NLS peptide with a specific 60-kDa NLS-binding protein from rat nuclear
      envelopes in photoaffinity labeling experiments. The antibody blocked the nuclear
      import of NLS-albumin conjugates in an in vitro nuclear transport assay with
      digitonin-permeabilized cells, but did not affect passive diffusion of a small
      non-nuclear protein, lysozyme, across the pore. Mab E2 may inhibit protein
      transport by directly interacting with the 60-kDa NLS-binding protein, thereby
      blocking signal-mediated nuclear import across the nuclear pore complex.

PMID- 7514537
TI  - Immunoelectron microscopy of RNA combined with nucleic acid cytochemistry in
      plant nucleoli.
AB  - The immunoelectron microscopy detection of RNA using anti-RNA monoclonal
      antibodies has been performed for the first time over different plant cells. The
      use of the methylation-acetylation (MA) method permits clear distinction among
      the nuclear and nucleolar compartments and can be combined with the immunogold
      approach. Cytochemical methods for nucleic acids were performed together with the
      immunoassays, providing additional data about the different composition of the
      various nucleolar components. Anti-RNA antibodies highly labeled the ribosome
      rich areas of the cytoplasm and the nucleolus. The interchromatin region also is
      labeled. The labeling was intense in the granular component, lower in the dense
      fibrillar component, and very scarce in the fibrillar centers. The MA method made
      possible the statistical evaluation of the labeling density in the various
      nuclear compartments by permitting the clear assignment of the particles to
      precise nuclear structures.

PMID- 7514539
TI  - PDGF-independent activation of PDGF-beta receptors in NIH-3T3 cells transformed
      by c-met protooncogene.
AB  - We have previously reported that c-met protooncogene, a member of a new class of
      receptor tyrosine-kinase gene family, is transforming when overexpressed in NIH
      3T3 cells. In this paper, we report that the c-met protooncogene-transformed
      cells proliferate in a serum- and growth factor-free medium and exhibit
      constitutive tyrosine phosphorylation of several cellular proteins including the
      met protooncogene-encoded p145 and p185. Further investigations revealed platelet
      derived growth factor (PDGF)-independent phosphorylation of PDGF-beta receptors
      in the transformed cells. Phosphoamino acid analysis revealed phosphorylation of
      PDGF receptors at tyrosine and serine residues. The PDGF receptor phosphorylation
      is unlikely to occur via autocrine production of PDGF since we could not detect
      PDGF activity both at the RNA level and at a functional protein level.
      Additionally, phospholipase C-gamma (PLC-gamma) a substrate of activated PDGF
      receptors, was found to be physically associated with PDGF receptors in the
      absence of PDGF stimulation in transformed cells. Furthermore, PDGF receptors
      coimmunoprecipitated along with PLC-gamma. Taken together, our results
      demonstrate a PDGF-independent phosphorylation and activation of PDGF-beta
      receptor in NIH-3T3 cells transformed by c-met protooncogene.

PMID- 7514540
TI  - Differences in tyrosine phosphorylation of oocyte key proteins during 5HT-induced
      meiosis reinitiation in two bivalve species.
AB  - The neurohormone serotonin (5HT) triggers meiosis reinitiation in oocytes of the
      pelecypod molluscs Spisula solidissima and Ruditapes philippinarum. However,
      while Spisula oocytes complete maturation, Ruditapes oocytes arrest in metaphase
      I. Anti-phosphotyrosine antibody revealed that serotonin triggered an early
      tyrosine phosphorylation of p42mapk which was transient in Spisula, but persisted
      in Ruditapes. Moreover, dephosphorylation of tyrosine residues of p34cdc2 was
      only observed in Spisula oocytes, simultaneously with germinal vesicle breakdown.
      The possibility is discussed that such differences may account for maintenance of
      the metaphase I block.

PMID- 7514538
TI  - Ni2+ blocks the Ca2+ influx in human keratinocytes following a rise in
      extracellular Ca2+.
AB  - In keratinocytes a rise in extracellular Ca2+ induces differentiation and is
      associated with a sustained increase in intracellular Ca2+, due to Ca2+ entry
      across the plasma membrane. We have investigated the mechanism of Ca2+ entry in
      human keratinocytes following this rise, using Fura-2-loaded cells and the
      cations Ni2+, Co2+, Mn2+, and La3+ and Ca2+ channel blocker verapamil.
      Keratinocytes were permeable to La3+, Mn2+, and Co2+; Fura-2 fluorescence was
      quenched by Mn2+ and Co2+. Verapamil was unable to block Ca2+ entry. Ni2+ did not
      enter keratinocytes, but blocked the influx of extracellular Ca2+ and Mn2+.
      Thapsigargin depleted Ca2+ stores, inducing a large transient intracellular rise,
      and the efflux of this Ca2+ was not blocked by Ni2+. We conclude that
      keratinocytes are permeable to a number of cations, but not Ni2+, which may be
      used to block the entry of the other cations during the study of cation flux into
      cells. The data presented are consistent with calcium entry by a nonspecific
      cation channel recently described on keratinocytes.

PMID- 7514541
TI  - Relevance of serum G-CSF levels in bone marrow transplantation patients.

PMID- 7514542
TI  - Effects of anti-CD44 monoclonal antibody on adhesion of erythroid leukemic cells
      (ELM-I-1) to hematopoietic supportive cells (MS-5): CD44, but not hyaluronate
      mediated, cell-cell adhesion.
AB  - Cocultivation of erythroid leukemic cells (ELM-I-1) with hemopoietic supportive
      cells (MS-5) resulted in a specific adhesion of ELM-I-1 cells to MS-5 cells. This
      phenomenon was designated as rosette formation. After induction of
      differentiation of ELM-I-1 cells, rosette formation was reduced, and no rosette
      formation was observed between erythrocytes and MS-5 cells. Studies on anti
      adhesion molecule antibody treatment have revealed that CD44 plays a key role in
      rosette formation. Expression of CD44 on (the membrane of) ELM-I-1 cells was
      reduced after differentiation, and no CD44 expression was detected on
      erythrocytes. CD44 was also expressed on MS-5. Hyaluronate is known as the ligand
      of CD44, but neither hyaluronidase treatment nor addition of excess hyaluronate
      to the assay system affected rosette formation. These data indicate that
      hyaluronate is not responsible for rosette formation. Anti-CD44 antibody (KM81),
      which recognized the hyaluronate binding site of CD44, inhibited rosette
      formation. But other monoclonal antibodies against different epitopes except for
      the hyaluronate binding site, even those against CD44's hyaluronate binding site,
      did not inhibit rosette formation. Thus, rosette formation between MS-5 cells and
      ELM-I-1 cells is mediated by CD44 but not by the hyaluronate binding site of
      CD44.

PMID- 7514543
TI  - Synergistic effect of stem cell factor with interleukin-3 or granulocyte
      macrophage colony-stimulating factor on the proliferation of murine primitive
      hematopoietic progenitors.
AB  - We examined the effect of recombinant murine stem cell factor (SCF) on murine
      primitive hematopoietic stem cells in vivo. Marrow cells from 5-fluorouracil (5
      FU)-treated male CBA/J mice were transplanted into lethally irradiated female
      littermates. Immediately after marrow transplant, the mice received SCF,
      interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM
      CSF) alone or in combination daily for 6 days. Day-12 colony-forming units-spleen
      (CFU-S) and marrow-derived colony-forming units-granulocyte/macrophage (CFU-GM)
      were assessed. Bone marrow cells from primary transplant recipients were
      transplanted into a secondary group of lethally irradiated mice, and the number
      of spleen colonies arising after 12 days' engraftment was determined as pre-CFU
      S. SCF alone did not increase spleen colony formation in either primary or
      secondary recipients. In contrast, treatment of primary recipients with SCF and
      GM-CSF or IL-3 or with all three cytokines resulted in a synergistic increase of
      CFU-S in secondary recipients, indicating increased pre-CFU-S levels. The
      cytokine combinations also produced synergistic increases of CFU-GM in primary
      recipient marrow. Evaluation of spleen colonies in secondary recipients by PCR
      amplification of the Y-chromosome sex-determining region indicated that about 80%
      were of donor (male) origin. We conclude that SCF with IL-3 and/or GM-CSF
      increases pre-CFU-S proliferation.

PMID- 7514544
TI  - Temporal profile of aminergic neurotransmitter release in striatal dialysates in
      rats with post-ischemic seizures.
AB  - The temporal profiles of aminergic neurotransmitter levels and of their acid
      metabolites after transient global cerebral ischemia in awake rats with and
      without subsequent seizures were compared using a microdialysis approach. In
      seizure animals, the post-ischemic levels of dopamine and serotonin were higher
      than the levels observed in the non-seizure controls. Inversely, the levels of
      the three neurotransmitter metabolites increased rapidly in the controls but not
      in seizure animals, where they remained at the low levels observed during and
      immediately after ischemia. This particular pattern is similar to that observed
      in rats submitted to prolonged ischemia or pretreated with monoamine oxidase
      inhibitors. In the seizure animals, neurotransmitter metabolites remained at low
      levels, as if the hypoxia had continued after the period of ischemia, inhibiting
      monoamine oxidase activity and, perhaps, neurotransmitter recapture.

PMID- 7514545
TI  - Receptor-binding domain of human alpha 2-macroglobulin. Expression, folding and
      biochemical characterization of a high-affinity recombinant derivative.
AB  - A recombinant version of the receptor binding domain (RBDv) of human alpha 2
      macroglobulin (alpha 2M) has been expressed in E. coli and refolded using a novel
      iterative procedure. RBDv (Val1299-Ala1451) is extended by 15 residues at the N
      terminal side of the Lys1313-Glu papain cleavage site in human alpha 2M. RBDv
      contains the intra-chain bridge Cys1329-Cys1444 and is soluble and monomeric.
      Competition experiments with 125I-labelled methylamine-treated alpha 2M reveal
      that RBDv binds to the placental receptor for transformed alpha 2M with a Kd of 8
      nM, i.e. the binding affinity of RBDv is of the same order of magnitude as the
      intrinsic affinity for binding of one domain in transformed alpha 2M to one
      receptor molecule.

PMID- 7514546
TI  - Identification of an aprotinin antiviral domain.
AB  - Digestion of the proteinase inhibitor aprotinin, by clostripain, a cysteine
      proteinase, yielded five oligopeptide fragments. Two fragments exhibited both
      antiviral and antibacterial activities, two fragments only antiviral activity,
      and one fragment showed no antimicrobial activity. One of the former
      oligopeptides showed antiviral activity against human herpes simplex virus type 1
      and bovine parainfluenza virus type 3. It consisted of the hexapeptide Y-F-Y-N-A
      K corresponding to amino acids 21-26 of intact aprotinin. An identical synthetic
      peptide had the same antiviral spectrum as the natural hexapeptide, exhibited no
      antibacterial activity, and was also devoid of trypsin inhibiting activity.
      Intact aprotinin, in contrast, is ineffective against human herpes simplex virus
      1 and bovine parainfluenza virus 3 but possesses antibacterial properties against
      several bacterial species [(1992) J. Appl. Bact. 72, 180-187].

PMID- 7514547
TI  - Declining beta-human chorionic gonadotropin level may provide false security that
      tubal pregnancy will not rupture.
AB  - Two patients with declining serum concentrations of beta-human chorionic
      gonadotropin (beta-hCG) and a ruptured tubal pregnancy with hemoperitoneum are
      described. Declining beta-hCG does not rule out the possibility that the ectopic
      pregnancy will rupture.

PMID- 7514548
TI  - TSH action on cAMP binding to the regulatory subunits of cAMP-dependent protein
      kinases in pig thyroid cell cultures.
AB  - This study examines the mechanism of TSH action on the cAMP-dependent protein
      kinases (PKA) by measuring the catalytic activity of the two PKA isozymes (PKA I
      and PKA II) and their capacity to bind cAMP to the regulatory subunits (RI and
      RII) in thyroid cell cultures exposed for two days to different doses of TSH. In
      TSH-treated cell cultures a selective down regulation (up to 60%) of the
      catalytic activity was found; the PKA I was down regulated at lower TSH doses
      (0.1 mU/ml and even 0.05 mU/ml) than was the PKA II (1.0 mU/ml TSH). At the dose
      of 1.0 mU/ml the loss of the catalytic activity in PKA I and PKA II was
      respectively 60% and 40%. No free catalytic activity was found either in control
      or in TSH-treated cells. Binding of cAMP to regulatory subunits (R) measured
      under exchange conditions at 37 degrees C, showed that no change in total
      regulatory subunit protein content occurs in TSH-treated cells. Binding of cAMP
      to R subunits at 4 degrees C (when only free cAMP binding sites are measured)
      revealed an important endogenous occupancy of cAMP binding sites of RI and RII
      isoreceptors under basal conditions (40%) and a significantly increased occupancy
      after exposure of cells to TSH (60%). Pools of regulatory subunits with more than
      50% of sites occupied, which were devoid of enzyme activity, were found both, in
      control and TSH-exposed cells. They were identified as RI subunits which
      represented a mixed population of native and partly degraded molecules.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7514549
TI  - PACAP-38 positively regulates glycoprotein hormone alpha-gene expression in
      placental cells.
AB  - The human glycoprotein hormone alpha-gene is transcriptionally activated by cAMP
      in placental cells. We have shown that the novel hypothalamic peptide, pituitary
      adenylate cyclase activating polypeptide, PACAP-38, significantly stimulates
      intracellular cAMP levels (12-fold increase; P < 0.001) in JEG-3 choriocarcinoma
      cells. Regulation of alpha-promoter activity was assessed using both the
      chloramphenicol acetyl transferase (CAT) and the luciferase (LUC) reporter gene
      systems. alpha-CAT activity was significantly stimulated by PACAP-38 (4-fold
      increase; P < 0.05) at 24 h with a similar stimulation being seen with a LUC
      expression vector. The kinetics of stimulation of the alpha-promoter by PACAP-38
      were similar to those seen with 8-Br-cAMP and vasoactive intestinal polypeptide
      (VIP), a peptide which shares 68% homology with PACAP-38. PACAP-38 also
      stimulated the production of IL-6 from JEG-3 cells with a time course of response
      similar to that of alpha-promoter transcription. We conclude that human placental
      choriocarcinoma cells possess functional receptors for PACAP-38, whose activation
      enhances cAMP formation, alpha-subunit gene transcription and interleukin-6 (IL
      6) production.

PMID- 7514550
TI  - Human pancreas-specific protein/procarboxypeptidase B: a useful serum marker of
      acute pancreatitis.
AB  - The aim of this study was to evaluate the serum behavior of human pancreas
      specific protein/procarboxypeptidase B (hPASP/PCPB) in the early phases of acute
      pancreatitis, and to calculate its sensitivity and specificity in comparison with
      those of serum amylase and lipase in the diagnosis of this illness. Twenty-six
      acute pancreatitis patients were studied; the pancreatitis was of biliary origin
      in 11, due to alcohol abuse in 8, and due to other causes in 7. Sixteen patients
      had mild pancreatitis and 10 the severe form of the disease. Thirty-one patients
      with nonpancreatic acute digestive diseases were also studied. Serum
      concentrations of hPASP/PCPB, amylase and lipase were determined in all subjects
      on admission to the study as well as daily for the following 5 days in acute
      pancreatitis patients. All patients with acute pancreatitis had abnormally high
      serum hPASP/PCPB, amylase and lipase concentrations on the first day of
      admission. On the sixth day of the disease, 76% of acute pancreatitis patients
      had abnormally high serum concentrations of hPASP/PCPB, whereas only 48% (p <
      0.05) had elevated serum amylase and lipase. No differences in serum levels of
      hPASP/PCPB, amylase or lipase were found between patients with alcoholic
      pancreatitis and those with other etiological forms of the disease, or between
      those with mild and severe forms of pancreatitis. The specificity of the three
      serum pancreatic protein assays, calculated on the 31 patients with nonpancreatic
      acute digestive diseases, was 90% for both hPASP/PCPB and lipase, 75% for
      amylase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514551
TI  - Alterations of the pancreatic secretory responses to secretin and to the
      ionophore A23187 by reserpine: a calcium-mediated phenomenon?
AB  - This study was undertaken to further characterize the secretory response of the
      rat pancreas after reserpine treatment. Rats were given reserpine (1 mg kg-1 day
      1 i.p.) or vehicle for 7 days. To distinguish between specific effects of
      reserpine and those related to secondary malnutrition caused by the drug, the
      secretory response of a group of pair-fed (PF) animals to reserpine was also
      investigated. Amylase release from dispersed pancreatic acini, prepared from
      control (C), PF and reserpine-treated (R) rats were used to evaluate functional
      secretory capacity. Reserpine and pair-feeding caused reduced responses of
      pancreatic acini to secretin. The pair-feeding-altered secretin response was
      greatly improved by increasing extracellular Ca2+ concentration, whereas a slight
      improvement was noticed in the R group. Reserpine significantly reduced the
      secretory response to the ionophore A23187 at concentrations above 5 x 10(-7) M
      in 1.25 mM Ca2+; in 2.5 mM Ca2+, the response to the ionophore was significantly
      higher in the R group than in C at all ionophore concentrations. Furthermore, at
      2 x 10(-7) M ionophore, the secretory response to secretin in the R group became
      significantly higher than that in the C group but comparable to that of the
      control+ionophore. In conclusion, reserpine affects the secretory response to
      secretin as did pre-exposure of pancreatic acini to a high concentration of
      carbamylcholine. The modified secretory response to the ionophore following
      reserpine treatment indicates that reserpine may act as a 'Ca2+ entry mechanism'
      antagonist which may explain the partial reduction in the secretin response.

PMID- 7514552
TI  - Canine model of chronic pancreatitis due to chronic ischemia.
AB  - An experimental model of chronic pancreatitis was produced by a chronic ischemia
      which was induced by ligation and separation of branches flowing into the left
      pancreatic lobe from the splenic artery. Macroscopic findings at 3 and 6 months
      after model preparation showed that the pancreas was hard, with severe
      inflammatory change. In the secretin-cerulein test at 3 and 6 months, the flow
      rate of pancreatic juice, amylase output and bicarbonate concentration were
      significantly reduced as compared with the controls. The histopathological
      findings consisted of a decrease in the pancreatic parenchyma, replacement of
      fat, severe inflammatory cell infiltration, extensive fibrosis and tubular
      complexes. As this model closely resembles human chronic pancreatitis, we
      conclude that ischemia is an etiological factor in chronic pancreatitis.

PMID- 7514553
TI  - Monitoring serum tryptic activity and effect of trypsin inhibitor on rat acute
      pancreatitis.
AB  - The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoethylthio)
      phenyl 4-guanidinobenzoate methanesulfonate (E3123), on severe acute pancreatitis
      was studied in trypsin-taurocholate-induced acute experimental pancreatitis in
      rats. Rats were divided into four groups according to difference of subdivided
      doses of E3123 with fixing the total dose at 3 mg/kg body weight. Group A: 1.5
      mg/kg of E3123 subcutaneously (SC) each at 1 h before and after induction of
      pancreatitis. Group B: 1 mg/kg SC each at 1 h before, 1 and 3 h after induction.
      Group C: 1.5 mg/kg SC each at 1 and 3 h after induction. Group D: 1.5 mg/kg SC
      each at 3 and 5 h after induction of pancreatitis. The survival rate at 24 h was
      significantly improved in group B (77% in group B, vs. 36% in paired control; p <
      0.01) and in group C (70 vs. 38%; p < 0.05), but not in group A or D. Residual
      tryptic activity of serum alpha 2-macroglobulin trypsin complex (alpha 2M-TRY)
      was reduced after the injection of E3123 though immunoreactive trypsin remained
      unchanged in the early phase of pancreatitis. The reduction of alpha 2M-TRY
      reflected the inhibitory capacity of E3123 in plasma. E3123 showed favorable
      effects on the initial stage of severe acute pancreatitis and the effects were
      probably based on the inhibition of alpha 2M-TRY activity in serum.

PMID- 7514554
TI  - Distribution of mRNA coding for alpha-2-macroglobulin, the murinoglobulins, the
      alpha-2-macroglobulin receptor and the alpha-2-macroglobulin receptor associated
      protein during mouse embryogenesis and in adult tissues.
AB  - The distribution of mRNA coding for the members of the wide-spectrum proteinase
      scavenging system of the alpha-2-macroglobulin family was examined in the mouse:
      Alpha-2-macroglobulin (MAM), the murinoglobulins (MUG), the alpha-2-macroglobulin
      receptor (alpha 2MR) and the receptor associated protein, the heparin binding
      protein-44 (alpha 2MRAP/HBP-44), a component of unknown function. The results
      demonstrate that MAM is expressed in the mouse embryo exclusively in the liver
      and not before day 13 of gestation. MUG mRNA was never detected during
      embryogenesis. On the other hand, both the alpha 2MR and the alpha 2MRAP/HBP-44
      messages were present throughout all embryonal stages examined. The distribution
      of the alpha 2MR mRNA was widespread in most tissues, with stronger signals
      observed in developing mouse brain, in whisker follicles and in the
      perifollicular mesenchyme, in lung, liver, kidney, intestine and placenta. The
      alpha 2MRAP/HBP-44 mRNA was detected predominantly in brain, lung, liver, kidney
      and placenta. Interestingly, within each tissue the cellular distribution of the
      alpha 2MR and alpha 2MRAP/HBP-44 mRNA was quite different with the most
      remarkable extremes observed in kidney and in placenta. The implication of these
      observations for receptor expression and function are discussed. Northern
      analysis of adult tissues extended these observations: major signals for MAM and
      MUG were seen only in liver, while the expression of the alpha 2MR and the alpha
      2MRAP/HBP-44 was widespread with highest levels of the 15-kb alpha 2MR mRNA in
      liver. Kidney was the most abundant source of alpha 2MRAP/HBP-44 mRNA with the
      1.8- and 3.6-kb mRNAs, derived from the same gene by alternative mRNA splicing,
      present in nearly constant ratios in most tissues, except in testis. The notable
      absence of expression of MAM in the first half of gestation indicates that during
      this period the receptor is scavenging for proteinases complexed to MAM derived
      from the maternal circulation or is being used for endocytosis of the other
      documented ligands, such as plasminogen activator complexes or apolipoprotein E
      containing lipoprotein particles.

PMID- 7514555
TI  - [Mapping the gene for palmoplantar hyperkeratosis (thylosis) to chromosome 17 in
      the 17q12-q24 region].
AB  - Mapping of the genetic defect causing dominant palmoplantaris hyperkeratosis
      (PPHK) was continued based on the material of an extended Uzbek pedigree. No
      linkage between the PPHK gene and hypervariable DNA markers from 8p, 12p, 14q,
      and 22q were revealed. The study of PPHK gene linkage with DNA markers covering
      the entire length of 17th chromosome mapped the PPHK gene to 17q12-q24 and
      revealed close linkage with KRT10 and D17S800 loci (zero recombination frequency
      at a lod score > 7). The possible location of a PPHK mutation in one of the
      keratin genes mapped to the same region on the 17th chromosome is discussed.

PMID- 7514556
TI  - [Identification of structural rearrangements in the karyotype of Microtus
      oeconomus from Chernobyl by differential staining of chromosomes].
AB  - Karyological studies of rodents within a 30-km radius of the Chernobyl' nuclear
      power plant revealed one female root vole (Microtus oeconomus) with an abnormal
      karyotype. The use of C, G, and AgNOR banding methods allowed us to determine
      that morphological changes in two nonhomologous autosomes, which were accompanied
      by rearrangements in distribution of G bands, heterochromatin, and NOR, are the
      result of a reciprocal translocation. Chromosomal aberrations were probably
      inherited or appeared in embryogenesis, since none of the analyzed cells of the
      studied vole had a normal karyotype. It is important to note that this
      rearrangement was detected five years after the meltdown. Both breaks and
      reunions of the chromosomes that participate in this rearrangement are probably
      located in regions that are not important for functioning of these chromosomes.
      Thus, it can be supposed that the detected rearrangement did not influence the
      viability of the vole. This karyotype was compared to a standard karyotype of a
      root vole from another area of the species range. The heteromorphism of the first
      pair of chromosomes in both voles, which was detected for the first time, is
      probably normal for the karyotype of M. oeconomus, and is not linked with any
      radiation-induced intrachromosomal aberrations.

PMID- 7514557
TI  - Chemotherapy of recurrent/advanced cervical cancer: results of the Yale
      University PBM-PFU protocol.
AB  - Chemotherapy for cervical cancer patients with recurrent and/or advanced disease
      has been complicated by excessive toxicity and short duration of responses,
      leading to little or no improvement in survival. Modification of drug scheduling
      and delivery of platinum, bleomycin, methotrexate, and 5-FU has resulted in a new
      combination regimen with little toxicity and a survival advantage for responders.
      PBM (platinum 80 mg/m2 D1, bleomycin 10 mu/m2/day D3-6, methotrexate 150 mg/m2
      D15, 22 with leucovorin) is alternated with PFU (platinum 100 mg/m2 D1, 5-FU 1000
      mg/m2/day D2-5) q 4 weeks for 3-6 months. The platinum, bleomycin, and 5-FU were
      delivered by continuous infusion. Twenty-three patients with recurrent and 17
      with advanced cervical cancer are evaluable; 91% of patients with recurrent
      disease had received prior radiation therapy. The response rate was 30.4% in
      those with recurrent disease, and 41.2% in those with advanced disease, with 86
      and 42.9% of responders respectively achieving a CR. Survival data were analyzed
      for each group separately, as well as for the combined recurrent/advanced disease
      group (N = 40). The results and significance were not changed by the groupings.
      In the combined recurrent/advanced group, median duration of response was 10.5
      months, mean 20.1, and the median overall survival was 11 months, mean 20.5 +/-
      3.5. There was a survival advantage accrued to the responders (median, 28 months)
      vs the nonresponders (10 months) (P = 0.0005 by log rank test). Moreover, there
      was a significant difference in progression-free interval between responders vs
      nonresponders (P = 0.0001), as well as between responders and those with stable
      disease (P = 0.001). This regimen was very well tolerated and there was no
      significant pulmonary toxicity. Furthermore, in the subset of 23 patients who had
      recurrent disease, 67% achieved palliation of pain. Experience with this protocol
      supports the continuing use of chemotherapy in the management of cervical cancer
      patients.

PMID- 7514558
TI  - Significance of specific antibody assay for genotyping of hepatitis C virus.
AB  - Group I and II hepatitis C virus genotypes were determined by a newly developed
      serological genotyping assay. This assay detected antibodies against group
      specific recombinant proteins in the putative NS4 protein region (amino acid no.
      1676-1760) by an enzyme-linked immunosorbent assay. This region of the hepatitis
      C virus peptide has many group-specific amino acids; fewer than 50% of these
      amino acids are identical between groups I and II. Genotypes determined by the
      serological genotyping assay were compared with those determined by a method in
      which the polymerase chain reaction was used in 91 chronic hepatitis patients.
      The group-specific polymerase chain reaction was performed within the genome
      region corresponding to the putative NS5 protein, where the group II hepatitis C
      virus genome is 57 nucleotides longer than that of group I. Among 91 chronic
      hepatitis C patients who had positive results in the second-generation hepatitis
      C virus antibody (core and NS3 region) assay, hepatitis C virus RNA was detected
      in 80 patients by polymerase chain reaction in the 5' untranslated region and in
      78 patients by this group-specific polymerase chain reaction. As a result, in 76
      of 91 patients (84%) genotypes determined by the serological genotyping assay
      showed complete agreement with those determined by the group-specific polymerase
      chain reaction, and none of the patients revealed a group opposite to that of
      hepatitis C virus genotype. The detection rate of the serological genotyping
      assay (89 of 91; 98%) was even higher than that of the polymerase chain reaction
      assay (78 of 91; 86%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514559
TI  - Immunohistochemical detection of Fas antigen in liver tissue of patients with
      chronic hepatitis C.
AB  - Apoptosis is a type of cell death that occurs in acute or chronic hepatitis. It
      has been suggested to be mediated through Fas antigen. To evaluate the role of
      apoptosis on liver injury of chronic hepatitis C, we studied the expressions of
      Fas antigen and hepatitis C virus antigen (core antigen) immunohistochemically.
      Forty liver biopsy samples from patients with type C chronic liver disease were
      immunostained for Fas antigen and hepatitis C virus antigen. Expression of Fas
      antigen was found mainly in the cytoplasm of hepatocytes, and these positive
      cells were found particularly among infiltrating lymphocytes at the advancing
      edges of "piecemeal necrosis." The histological activity index showed
      inflammation of both portal and periportal areas to be more severe in the Fas
      antigen-positive samples than in the Fas antigen-negative ones (p < 0.05 and p <
      0.001, respectively). Furthermore, semiquantitative analysis revealed more
      expression of Fas antigen in the liver tissues with active inflammation than in
      those without it (p < 0.01). The prevalence of Fas antigen expression in the
      hepatitis C virus antigen-positive group was higher than that in the hepatitis C
      virus antigen-negative group (p < 0.05). Our findings suggest that Fas antigen
      expression (apoptosis) plays an important role in inflammation in the hepatitis C
      virus-infected liver, particularly in the active inflammation of chronic
      hepatitis C.

PMID- 7514560
TI  - Hepatitis C virus replication and antibody responses toward specific hepatitis C
      virus proteins.
AB  - We assessed the correlation between hepatitis C virus replication and antibody
      responses toward hepatitis C virus core (C22-3), NS3 (C33C), NS4 (5-1-1 and C100
      3) and NS5 proteins in 59 virus carriers. The concentration of serum hepatitis C
      virus RNA was determined by a competitive reverse transcription-polymerase chain
      reaction assay. All 50 patients with high viremic levels of > or = 10(6)
      copies/mL had antibodies to C22-3 and C33C. Antibodies to 5-1-1, C100-3 and NS5
      proteins were detected less frequently (p < 0.01) in 72% (36 of 50), 78% (39 of
      50) and 84% (32 of 38) of such patients, respectively. As for the nine patients
      with low viremic levels of < 10(6) copies/mL, antibodies to C22-3, C33C, 5-1-1
      and NS5 proteins were detected in only one patient (11%), which was significantly
      less than the frequency for highly viremic patients (p < 0.01). Antibody to C100
      3 was also found less frequently in only four patients (44%) (p < 0.05). Thus,
      only four (44%) of the nine low viremic patients tested positive for any antibody
      compared with all 50 highly viremic patients (p < 0.01). These results indicate
      that highly viremic carriers can be detected by the presence of hepatitis C virus
      antibodies, but a considerable proportion of low viremic carriers may not show
      any serological evidence of hepatitis C virus infection.

PMID- 7514561
TI  - Bile acid metabolism and biliary secretion in patients receiving orthotopic liver
      transplants: differing effects of cyclosporine and FK 506.
AB  - Bile acid metabolism and biliary secretion were characterized in the first 2 wk
      after orthotopic liver transplantation in 15 patients receiving cyclosporine and
      in five patients receiving FK 506. Analyses were performed on hepatic bile
      obtained by T-tube drainage; values obtained were compared with literature values
      for bile samples obtained in patients who had undergone cholecystectomy. Biliary
      bile acid output, which is equivalent to bile acid biosynthesis from cholesterol,
      was low (mean +/- S.E.M.) and increased with time: day 1, 0.50 +/- 0.1 mmol/day;
      day 3, 0.8 +/- 0.1 mmol/day; and day 6, 1.6 +/- 0.5 mmol/day. Chenodeoxycholic
      acid biosynthesis, as percent of total bile acid biosynthesis, was abnormally low
      in patients receiving cyclosporine (16.2 +/- 1.1) but not in patients receiving
      FK 506 (38.2 +/- 4.8) (p < 0.005). Before the T-tube was clamped, the proportion
      of deoxycholic acid (a secondary bile acid formed by bacterial 7-dehydroxylation
      of cholic acid) was low in both groups: cyclosporine, 0.4 +/- 0.1; FK 506, 4.8 +/
      2.5 (p < 0.01). The mean concentration of bile acids in hepatic bile between
      days 4 and 11 did not differ significantly between groups: cyclosporine, 7.7 +/-
      1.3 mmol/L; FK 506 4.3 +/- 0.7 mmol/L (mean +/- S.E.M.). (These values are
      similar to those reported for patients who have undergone cholecystectomy.) Bile
      acid-dependent bile flow, expressed as apparent choleretic activity (microliters
      of bile per micromole of bile acid output), was markedly elevated: in patients
      receiving cyclosporine the value was 129, and in patients receiving FK 506 the
      value was 220. (In patients who have undergone cholecystectomy, this value is
      less than 30).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514563
TI  - Serum alpha-L-fucosidase activity and tumor size in hepatocellular carcinoma.
AB  - The serum level of alpha-L-fucosidase activity has been suggested as a useful
      marker in the diagnosis of hepatocellular carcinoma, although the precise
      mechanism behind the elevation of this parameter has not been determined. We
      found that the serum alpha-L-fucosidase activity level was significantly higher
      in 67 patients with hepatocellular carcinoma (695.1 +/- 245.5 nmol/ml/hr) than in
      47 patients with cirrhosis (389.1 +/- 188.2 nmol/ml/hr; p < 0.001) and in 54
      controls (202.0 +/- 104.6 nmol/ml/hr; p < 0.001). However, alpha-L-fucosidase
      activity was not correlated with tumor size (r = 0.134), whereas the alpha
      fetoprotein level was correlated with tumor size (r = 0.580, p < 0.001). When
      515.8 nmol/ml/hr was taken as the cutoff value (mean value in the controls plus 3
      standard deviations), alpha-L-fucosidase activity was above the cutoff value in
      12 of the 17 patients with a hepatocellular carcinoma less than 2 cm in diameter,
      in 28 of the 37 patients with a hepatocellular carcinoma less than 3 cm in
      diameter and in 52 of the 67 patients with hepatocellular carcinoma. In contrast,
      only 10 of the 47 patients with cirrhosis had levels above the cutoff value.
      These findings suggest that an increase in serum alpha-L-fucosidase activity in
      patients with cirrhosis may be a marker for detecting a hepatocellular carcinoma,
      especially a small tumor, because alpha-fetoprotein and des-gamma-carboxy
      prothrombin are less promising as tumor markers.

PMID- 7514564
TI  - Localization of the interferon-induced, 2-5A-dependent RNase gene (RNS4) to human
      chromosome 1q25.

PMID- 7514562
TI  - Characterization of human hepatocyte lines derived from normal liver tissue.
AB  - Four separate continuous lines of human hepatocytes (HH01, HH02, HH09, HH25) were
      developed from normal liver tissue by subjecting cocultures of human hepatocytes
      with rat liver epithelial cells in a highly enriched medium to frequent
      subculturing. The addition of conditioned medium from either the human hepatoma
      line Hep G2 or one of these stable human hepatocyte lines (HH09) appeared to
      facilitate establishment of line HH25. These human hepatocyte lines have been in
      continuous culture for 2 to 5 yr and consist of approximately 95% human cells by
      analysis of cell surface antigens. Cytogenetic analysis also confirmed the human
      origin of these cells and showed clonal origin with abnormal ploidy. Cells in
      these human hepatocyte lines retain morphological features of hepatocytes by both
      light and electron microscopy. They also retain glucose-6-phosphatase activity
      and secrete proteins characteristic of hepatocytes, such as albumin, alpha
      fetoprotein and transferrin. After incubation with 13 mumol/L dibenz(a,h)
      anthracene for 24 hr, each line had detectable activity of aryl hydrocarbon
      hydroxylase, ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase.
      Thus, these human hepatocyte lines retain important differentiated
      characteristics of hepatocytes. Derived from normal liver tissue, they appear to
      be immortalized. They provide a new model system for studying human
      hepatocellular drug metabolism. These lines may also be useful for studying the
      regulation of synthesis of albumin, alpha-fetoprotein and other proteins in human
      hepatocytes, determining the effects of cytokines and growth factors and
      designing systems to effect gene transfer into human hepatocytes for the purpose
      of gene therapy.

PMID- 7514565
TI  - Localization of the human gene for inducible nitric oxide synthase (NOS2) to
      chromosome 17q11.2-q12.

PMID- 7514566
TI  - Gene mapping in a murine cell line by immunoselection with cytotoxic T
      lymphocytes.
AB  - Minor histocompatibility (H) loci encode alloantigens that are recognized by
      cytotoxic T (Tc) lymphocytes. A (C57BL/10 x 129)F1-derived transformed lymphocyte
      cell line was immunoselected in vitro with cloned Tc cells that were specific for
      H-3aa, a Chromosome 2-encoded minor H antigen. This cell line is heterozygous at
      H-3a (former symbol, Cd-1) and other loci. Three groups of antigen-loss variants
      were identified. One group contained mutations affecting only the antigen
      encoding gene. Another group probably arose through a single homologous
      interchromosomal exchange, resulting in extensive regions of loss of
      heterozygosity (LOH). The third group of variants contained an interstitial LOH,
      one of which was shown to be a significant deletion. Several deletion boundaries
      were identified, one of which ordered the closely linked H-3a and beta 2
      microglobulin (B2m) genes. We suggest that Tc immunoselection against minor H
      antigens is a promising approach for targeting negative selection to specified
      chromosomal regions and can provide high-resolution genetic map information.

PMID- 7514567
TI  - Two-locus linkage analysis in multiple sclerosis (MS).
AB  - One of the major challenges in genetic linkage analyses is the study of complex
      diseases. We demonstrate here the use of two-locus linkage analysis in multiple
      sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a
      set of Finnish multiplex families, we have previously found evidence for linkage
      between MS susceptibility and two independent loci, the myelin basic protein gene
      (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families
      provides a unique opportunity to perform linkage analysis conditional on two loci
      contributing to the disease. In the two-trait-locus/two-marker-locus analysis,
      the presence of another disease locus is parametrized and the analysis more
      appropriately treats information from the unaffected family members than single
      disease-locus analysis. As exemplified here in MS, the two-locus analysis can be
      a powerful method for investigating susceptibility loci in complex traits, best
      suited for analysis of specific candidate genes, or for situations in which
      preliminary evidence for linkage already exists or is suggested.

PMID- 7514568
TI  - Isolation and chromosomal localization of the human endothelial nitric oxide
      synthase (NOS3) gene.
AB  - Nitric oxide (NO) is an important intercellular signaling molecule synthesized in
      diverse human tissues by proteins encoded by a family of NO synthase (NOS) genes.
      The similarity of sequence and cofactor binding sites has suggested that the NOS
      genes may also be related to cytochrome P450 reductase, as well as to plant and
      bacterial oxidoreductases. Endothelial NOS activity is a major determinant of
      vascular tone and blood pressure, and in several important (and sometimes
      hereditary) disease states, such as hypertension, diabetes, and atherosclerosis,
      the endothelial NO signaling system appears to be abnormal. To explore the
      relationship of the endothelial NOS gene to other similar genes, and to delineate
      the genetic factors involved in regulating endothelial NOS activity, we isolated
      the human gene encoding the endothelial NOS. Genomic clones containing the 5' end
      of this gene were identified in a human genomic library by applying a polymerase
      chain reaction (PCR)-based approach. Identification of the human gene for
      endothelial NOS (NOS3) was confirmed by nucleotide sequence analysis of the first
      coding exon, which was found to be identical to its cognate cDNA. The NOS3 gene
      spans at least 20 kb and appears to contain multiple introns. The transcription
      start site and promoter region of the NOS3 gene were identified by primer
      extension and ribonuclease protection assays. Sequencing of the putative promoter
      revealed consensus sequences for the shear stress-response element, as well as
      cytokine-responsive cis regulatory sequences, both possibly important to the
      roles played by NOS3 in the normal and the diseased cardiovascular
      system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514569
TI  - The stop mutation R553X in the CFTR gene results in exon skipping.
AB  - Stop or nonsense mutations are known to disrupt gene function in a number of
      different ways. We have studied the effects of the stop mutation R553X in exon 11
      of the CFTR gene by analyzing mRNA extracted from nasal epithelial cells
      harvested from patients with cystic fibrosis. Four patients who were compound
      heterozygotes for the R553X mutation were studied. Ten non-CF control subjects
      were also studied. In all four patients, full-length CFTR mRNA was identified,
      but only a very small proportion of this was derived from the R553X allele. A
      smaller transcript, lacking exon 11, was also seen in the R553X patients but not
      in the controls. Most of this transcript was derived from the R553X allele. These
      results suggest that the R553X mutation results in skipping of the exon in which
      it is located.

PMID- 7514570
TI  - Mapping of the gene for inducible nitric oxide (NO) synthase of mouse macrophages
      to chromosome 11, close to Evi-2, nu, and Idd-4.

PMID- 7514571
TI  - Construction of a yeast artificial chromosome contig encompassing the human
      acidic fibroblast growth factor (FGF1) gene: toward the cloning of the ANLL/MDS
      tumor-suppressor gene.
AB  - The region surrounding the human acidic fibroblast growth factor (FGF1) locus on
      chromosome 5q31 is of particular interest since it represents a critical region
      consistently lost in acute nonlymphocytic leukemia (ANLL) or myelodysplastic
      syndrome (MDS) patients who have a demonstrable deletion of the distal portion of
      the long arm of chromosome 5. It is proposed that an ANLL/MDS leukemia suppressor
      gene resides on 5q31. We have previously shown that the gene is most likely
      localized between FGF1 and PDGFRB/CSF1R loci. The region has also been linked to
      at least four other genetic diseases, Treacher Collins syndrome, diastrophic
      dysplasia, limb-girdle muscular dystrophy, and an autosomal dominant deafness, by
      linkage analysis. Here, we describe yeast artificial chromosomes (YAC) spanning
      450 kb around the FGF1 gene. Six YAC clones were isolated from a human YAC
      library and their restriction enzyme maps were determined. The overlap of the
      clones with each other and with FGF1 cosmid and phage clones was characterized.
      Three of the YAC clones were found to contain the entire FGF1 gene, which spans
      more than 100 kb. Proximal and distal ends of several of these YAC clones were
      isolated for further overlap cloning. The proximal ends of both Y2 and Y4 were
      localized to previously isolated FGF1 DNA by sequence analysis. The distal ends
      of these two clones also hybridized to a human-hamster hybrid containing
      chromosome 5 as the only human genetic material. These results suggest that these
      YAC clones represent colinear DNA around the FGF1 locus.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7514572
TI  - Detection of polymorphisms within the Fas cDNA gene sequence by GC-clamp
      denaturing gradient gel electrophoresis.

PMID- 7514573
TI  - Single Dd amino acid substitutions in the H-2Ld molecule identify antibody
      epitopes.

PMID- 7514574
TI  - Entrance and survival of Salmonella typhimurium and Yersinia enterocolitica
      within human B- and T-cell lines.
AB  - Lymphocytes, located within the Peyer's patches, might be involved in the
      dissemination of enteropathogenic Salmonella typhimurium and Yersinia
      enterocolitica bacteria. To test this hypothesis, we have investigated the
      susceptibility of human B- and T-cell lines to bacterial adhesion and invasion.
      The two S. typhimurium strains analyzed were highly invasive, while the two Y.
      enterocolitica (O:8) strains adhered to the B- and T-cell lines but did not enter
      the cell lines in significant amounts. We hypothesize that the incapability of
      the Y. enterocolitica (O:8) strains to enter the human B- and T-cell lines is
      most probably due to the bacterial inability to induce the internalization
      process upon adhesion to both cell lines. Although immortalized B- and T-cell
      lines were used in this study, the results presented suggest the possibility that
      both cell types could play a role in the dissemination of intracellularly
      residing S. typhimurium in vivo.

PMID- 7514576
TI  - A lytic monoclonal antibody to Trypanosoma cruzi bloodstream trypomastigotes
      which recognizes an epitope expressed in tissues affected in Chagas' disease.
AB  - It has been suggested that molecular mimicry between the antigens of Trypanosoma
      cruzi and the host could have a role in the onset of the chronic stage of Chagas'
      disease. In this article, we report on a monoclonal antibody (MAb), CAK20.12
      (immunoglobulin G2b), which reacts with a polypeptidic epitope of a 150-kDa
      antigen expressed on the surface of several strains of T. cruzi. This MAb also
      causes lysis of bloodstream trypomastigotes. Serum samples from 30 of 30 patients
      with chronic and 11 of 13 patients with acute Chagas' disease present specific
      antibodies to this antigen. MAb CAK20.12 reacts, by indirect immunofluorescence,
      with human and syngeneic murine striated muscle tissue, with the smooth muscle
      layer of cardiac arteries, with the lamina muscularis mucosae and the external
      striated muscle layer of the esophagus, and with the smooth muscle cells of the
      colon from normal syngeneic mice. Reactivity with the small intestine was very
      weak, and no reactivity with ventricle or atrium tissue was detected. Adsorption
      with an antigenic fraction from normal murine striated muscle or from T. cruzi
      epimastigotes confirmed that MAb CAK20.12 recognizes a common epitope present in
      parasites and host tissues. MAb CAK20.12, lytic for the infective form of T.
      cruzi, recognizes an epitope expressed in striated and smooth muscle cells of the
      host tissues affected in the chronic stage of Chagas' disease.

PMID- 7514577
TI  - Leukotriene B4 generation and DNA fragmentation induced by leukocidin from
      Staphylococcus aureus: protective role of granulocyte-macrophage colony
      stimulating factor (GM-CSF) and G-CSF for human neutrophils.
AB  - We studied the effect of leukocidin from Staphylococcus aureus V8 strains (Luk
      PV) on the generation of Leukotriene B4 (LTB4) and its metabolites from human
      polymorphonuclear neutrophils (PMNs). Significant amounts of LTB4 were generated
      by PMNs after leukocidin exposure in a time- and dose-dependent manner, as shown
      by reversed-phase high-performance liquid chromatography analysis. In this
      regard, the S and F components of leukocidin acted synergistically. The calcium
      ionophore A23187 induced LTB4 generation, and the metabolism of exogenously added
      LTB4 into biologically less active omega-oxidated compounds was significantly
      decreased after leukocidin exposure. Priming of PMNs with granulocyte-macrophage
      colony-stimulating factor (GM-CSF) or G-CSF prior to leukocidin exposure
      substantially increased toxin- and calcium ionophore A23187-induced LTB4
      formation. The inhibitory effects of leukocidin on mediator release were
      accompanied by membrane damage and DNA fragmentation, which were both restored
      after pretreatment with GM-CSF. The data suggest that the presence of
      costimulatory priming factors such as GM-CSF or G-CSF in the microenvironment of
      an inflammatory focus determines the pathophysiological effects induced by S.
      aureus leukocidin.

PMID- 7514575
TI  - The 70-kilodalton pertussis toxin-binding protein in Jurkat cells.
AB  - 125I-ASD photoaffinity-labeling derivatives of pertussis toxin (125I-ASD-PT) or
      lipopolysaccharide (125I-ASD-LPS) labeled similar 70-kDa proteins in Jurkat
      cells, a cell line derived from human CD4+ T lymphocytes. Labeling of this 70-kDa
      protein by 125I-ASD-PT was inhibited by underivatized PT but not by underivatized
      LPS. However, an immunoglobulin M monoclonal antibody with specificity for the
      p73 LPS receptor in murine splenocytes (S. W. Bright, T.-Y. Chen, L. M. Flebbe,
      M.-G. Lei, and D. C. Morrison, J. Immunol. 145:1-7, 1990) inhibited 125I-ASD-PT
      labeling of the 70-kDa species in Jurkat cells. Our results suggested that PT may
      bind to the same 70-kDa protein as LPS does in Jurkat cells but that PT and LPS
      bind to different sites on this receptor candidate. 125I-ASD-PT photoaffinity
      labeling of the 70-kDa protein was also inhibited by underivatized glycoproteins
      to which PT has been shown to bind, and this inhibition correlated with the
      relative binding affinities of the glycoproteins for PT. 125I-ASD derivatives of
      two sialic acid-specific plant lectins, Maackia amurensis leukoagglutinin and
      Sambucus nigra agglutinin, with oligosaccharide binding specificities similar to
      those of PT also labeled a 70-kDa protein in Jurkat cells. This suggests that the
      70-kDa PT receptor candidate in Jurkat cells likely contains sialooligosaccharide
      sequences to which PT, M. amurensis leukoagglutinin, and S. nigra agglutinin
      bind. The cross-reacting epitope recognized by monoclonal antibody 5D3 in this 70
      kDa species might overlap the PT- and LPS-binding sites.

PMID- 7514578
TI  - CS31A capsule-like antigen as an exposure vector for heterologous antigenic
      determinants.
AB  - CS31A is a multimeric surface protein surrounding certain enterotoxigenic and
      septicemic bovine Escherichia coli strains. The possibility of using CS31A as a
      carrier of foreign antigenic determinants was investigated. Introduction of
      heterologous viral epitopes into the CS31A major subunit, ClpG, was successfully
      performed in the V3 region of the molecule which encodes for an immunodominant
      linear epitope. E. coli K-12 strains producing the hybrid CS31A molecules or the
      purified chimeric proteins were used for mice immunization. By using the C
      epitope derived from the S protein of the porcine transmissible gastroenteritis
      virus, significant antiviral antibody titers were elicited and seroneutralization
      of the virus was demonstrated, confirming that the molecular environment in V3 is
      favorable for antigen presentation. These results indicate that synthesis of
      CS31A hybrid proteins by the wild-type strain 31A could become a powerful tool
      for the development of oral vaccines directed against mucosal pathogens.

PMID- 7514580
TI  - Effect of tenoxicam and indomethacin on the chemotaxis induced by substance P and
      interleukin-8 on human monocytes and polymorphonuclear cells.
AB  - The neuropeptide substance P and the cytokine interleukin-8 are potent
      chemotactic factors for monocytes and/or polymorphonuclear cells. They are
      present in the synovial fluid of arthritic patients, and participate in the
      pathogenesis of arthritis. We investigated in vitro the effect of two non
      steroidal antiinflammatory drugs, tenoxicam and indomethacin, on the chemotactic
      effect of substance P and interleukin-8 at concentrations that can be reached in
      the synovial fluid of arthritic patients. Both drugs decreased the chemotaxis
      induced by substance P and interleukin-8 at concentrations that can be reached in
      the synovial fluid during therapy. This result could be of importance for the use
      of these two non-steroidal antiinflammatory drugs in studying the development and
      progress of arthritic disease.

PMID- 7514581
TI  - Iris pigmentation and extent of disease in patients with neovascular age-related
      macular degeneration.
AB  - PURPOSE: To determine whether the extent of disease in age-related macular
      degeneration (AMD) varies with iris pigmentation. METHODS: The authors assessed
      visual function and macular appearance in the fellow eye or both eyes of 132
      white patients with unilateral neovascular AMD. All patients had a visual acuity
      of 20/60 or better in the fellow eye. Eighty-nine of the patients were coded as
      having light irides (blue, green, or hazel) and 43 were coded as having dark
      irides (brown); the two groups of patients had comparable mean ages. RESULTS: By
      the Mann-Whitney test for differences in mean rank, fellow eyes with light irides
      showed a marginally worse visual acuity (P = .156) but significantly more visual
      field impairment by letter recognition perimetry (P = .011) and the macular
      threshold test of the Humphrey Field Analyzer (P = .043), and more retinal
      pigment epithelial atrophy (P = .017) and focal areas of hyperpigmentation (P =
      .002) than fellow eyes with dark irides. For eyes with a choroidal neovascular
      membrane (CNVM), those with light irides had significantly lower visual acuities
      (P = .006) and larger scars (P = .006) than eyes with dark irides. In addition,
      extent of disease in the eye with a CNVM was positively correlated with extent of
      disease in the fellow eye for most comparisons. CONCLUSIONS: These observations
      suggest that light iris pigmentation is associated with more extensive retinal
      disease in patients with unilateral neovascular AMD. Furthermore, in such
      patients, those with worse disease in the eye with a CNVM may tend to have more
      extensive atrophic disease in the fellow eye.

PMID- 7514579
TI  - Relationship of tumor necrosis factor alpha, the nitric oxide synthase pathway,
      and lipopolysaccharide to the killing of gamma interferon-treated macrophage-like
      RAW264.7 cells by Rickettsia prowazekii.
AB  - Macrophage-like RAW264.7 cells are killed by the combination of gamma interferon
      (IFN-gamma) treatment and infection with Rickettsia prowazekii. The roles of
      tumor necrosis factor alpha (TNF-alpha), the nitric oxide synthase pathway, and
      lipopolysaccharide (LPS) in this killing were investigated. R. prowazekii, both
      the Breinl and Madrid E strains, induced RAW264.7 cells to produce TNF-alpha.
      However, dead rickettsiae (which cannot kill the IFN-gamma-treated RAW264.7
      cells) induced the production of as much TNF-alpha as viable rickettsiae.
      Inhibition of the production of TNF-alpha (by the addition of actinomycin D or
      emetine during the rickettsial infection) or neutralization of TNF-alpha (by the
      addition of polyclonal rabbit anti-mouse TNF-alpha serum both during the IFN
      gamma treatment and during the rickettsial infection) did not inhibit the killing
      of the RAW264.7 cells. Addition of polymyxin B (which inhibits many effects of
      LPS) during the IFN-gamma treatment did not inhibit the ability of IFN-gamma to
      prepare the RAW264.7 cells to be killed by R. prowazekii. Suppression of nitrite
      production by addition of the nitric oxide synthase inhibitor aminoguanidine both
      during the IFN-gamma treatment and during the rickettsial infection also did not
      inhibit the killing of the RAW264.7 cells. R. prowazekii-mediated killing of the
      RAW264.7 cells was dramatically suppressed in cultures treated with IFN-gamma
      plus LPS compared with that in cultures treated with IFN-gamma alone, and
      inhibition of nitric oxide synthase restored the rickettsia-induced killing of
      the RAW264.7 cells in cultures treated with IFN-gamma plus LPS. These data
      indicate that (i) TNF-alpha, LPS, and the nitric oxide synthase pathway are not
      required in order for IFN-gamma to prepare RAW264.7 cells to be killed by R.
      prowazekii; (ii) neither TNF-alpha nor the nitric oxide synthase pathway is
      responsible for the killing of the IFN-gamma-treated RAW264.7 cells by R.
      prowazekii; and (iii) in cultures treated with IFN-gamma plus LPS and then
      incubated with rickettsiae, a nitric oxide synthase pathway-dependent mechanism
      inhibits the killing of the RAW264.7 cells.

PMID- 7514582
TI  - The role of fibronectin, laminin, vitronectin and their receptors on cellular
      adhesion in proliferative vitreoretinopathy.
AB  - PURPOSE: To examine the possible role of some adhesion multifunctional
      glycoproteins of the extracellular matrix, such as fibronectin (FN), laminin
      (LN), vitronectin (VN) and their receptors (beta 1-subunit complex and alpha v
      beta 3 integrins) in events of cell migration and adhesion in proliferative
      vitreoretinopathy (PVR). METHODS: Optical and electron-immunocytochemical
      techniques were carried out on epiretinal membranes. Electrophoretic
      immunoblotting methods and densitometric analysis of normal and PVR vitreous were
      also undertaken. Chi-square (chi 2) and unbalanced analysis of variance were
      employed for statistical analysis. RESULTS: FN was detected as a major component
      in the extracellular matrix in both fibrillar and pericellular arrangement. A
      change in pericellular distribution to more fibrillous organization was related
      to the time of intraocular proliferative tissue development (P < 0.001). LN and
      VN were observed as minor components in extracellular matrix. A colocalized
      pattern between VN and FN in collagenic bundles of the matrix was often observed.
      Beta-1 subunit and alpha v beta 3 receptors were usually localized in a position
      that could mediate the interaction of FN, VN, and/or LN to the cell plasma
      membrane. Increased levels of FN concentration were observed in both subretinal
      fluid and pathologic vitreous; intravitreal FN concentration tends to increase
      with clinical stages of the evolution of PVR, whereas intravitreal VN levels tend
      to decrease. CONCLUSIONS: Results suggest that FN could mediate the initial
      events involved in epiretinal membrane formation, and VN could modulate the
      adhesion mechanisms in established membranes.

PMID- 7514583
TI  - The immunologic staging of chronic active hepatitis B patients in Hawaii.
AB  - The hepatitis B antigen/antibody levels and natural killer cell activity status
      of chronic hepatitis B patients identified by the Hawaii State Department of
      Health were evaluated to select chronically infected hepatitis B patients for
      interferon therapy and to determine possible immunodeficiencies. The presence of
      hepatitis Be antigen denotes active replication of the virus. Ninety-five
      patients were studied: 17/95 (18%) had chronic active hepatitis B, 71/95 (75%)
      were hepatitis B carriers and 7/95 (7%) had seroconverted. NK activity to the
      erythroleukemia K562 cell and virus-infected HSV-1 cell of the chronic active and
      carrier population (P < .05) were lower than that of the control population and
      those who had spontaneously seroconverted. Of this population 18% were identified
      with active viral infection and would be candidates for interferon therapy.

PMID- 7514584
TI  - Fas ligand and Fas: a death factor and its receptor.

PMID- 7514585
TI  - Inhibitory effects of (-)-epigallocatechin gallate on spontaneous hepatoma in
      C3H/HeNCrj mice and human hepatoma-derived PLC/PRF/5 cells.
AB  - The inhibitory effect of (-)-epigallocatechin gallate (EGCG), a main constituent
      of Japanese green tea, on spontaneous hepatoma in C3H/HeNCrj mice was
      investigated. A total of 72 mice were divided into three groups; the control
      group without EGCG, and two experimental groups receiving 0.05% (w/w) or 0.1%
      EGCG in drinking water. EGCG reduced the incidence of hepatoma-bearing mice from
      83.3% (control) to 56.0% (0.05% EGCG) and 52.2% (0.1% EGCG), and also reduced the
      average number of hepatomas per mouse from 1.83 (control) to 0.72 (0.05% EGCG)
      and 0.91 (0.1% EGCG) at week 65. Ridit analysis of the distribution of the number
      of hepatomas in each group revealed that EGCG significantly increased the rate of
      mice without hepatoma in the two EGCG groups as compared to the control. EGCG did
      not affect body weight gain, food consumption or any serum biochemical parameter.
      EGCG inhibited the growth and secretion of alpha-fetoprotein by human hepatoma
      derived PLC/PRF/5 cells without decreasing their viability. These results
      indicate that EGCG may be a practical, nontoxic preventive agent against human
      hepatoma.

PMID- 7514587
TI  - Human androgen receptor binding to the androgen response element of prostate
      specific antigen.
AB  - This study examined the in vitro interaction of the human androgen receptor with
      a putative androgen response element (ARE) in the promoter region of the prostate
      specific antigen (PSA) gene. To characterize the androgen receptor's interactions
      with its DNA response elements we expressed the full length human androgen
      receptor protein in a baculovirus expression system. The receptor was shown to be
      110 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      and was purified using ion-exchange column chromatography. Binding of the
      synthetic androgen R1881 to the unpurified recombinant receptor exhibited a kd of
      7.6 nM by Scatchard analysis. In DNA gel electromobility shift assays the
      promoter region from PSA (a 313-bp fragment) was bound by the unpurified
      recombinant androgen receptor in a sequence-specific manner. An ARE-containing
      sequence from the promoter region of the PSA gene was synthesized as a 30-bp
      oligonucleotide and was shown to bind specifically to the human androgen receptor
      in gel electromobility shift assays by DNA competition and by antibody
      supershifts of the receptor-ARE complex. The specific binding of the insect cell
      expressed androgen receptor to its ARE was shown to occur even in the absence of
      androgen. Androgen receptors purified by ion-exchange chromatography were unable
      to bind to ARE, suggesting the presence of other factors required for DNA
      binding.

PMID- 7514588
TI  - Ototoxicity in vitro: effects of neomycin, gentamicin, dihydrostreptomycin,
      amikacin, spectinomycin, neamine, spermine and poly-L-lysine.
AB  - The effects that the aminoglycoside-aminocyclitol antibiotics amikacin,
      dihydrostreptomycin, gentamicin, neomycin, and spectinomycin, the neomycin
      fragment neamine, and the polybasic compounds spermine and poly-L-lysine, have on
      outer hair cells in cochlear cultures prepared from the early post-natal mouse
      have been assessed using both scanning and transmission electron microscopy (SEM
      and TEM). The antibiotics were used at concentrations ranging from 0.25-1.0 mM,
      spermine from 10 microM to 3.0 mM, and poly-L-lysine from 0.05-2 microM.
      Qualitative assessment of apical surface damage allows the antibiotics to be
      ranked in the following order: neomycin > gentamicin > dihydrostreptomycin >
      amikacin > neamine > spectinomycin. At a concentration of 1 mM spectinomycin is
      essentially non-toxic and the effects of neamine are marginal. Poly-L-lysine and
      spermine also cause surface damage, with poly-L-lysine being substantially more
      toxic than any of the antibiotics, and spermine ranking, on the basis of SEM
      observations, between dihydrostreptomycin and amikacin. TEM indicates that
      although all toxic compounds cause damage to the apical surface of the hair cell,
      only neomycin, poly-L-lysine and spermine induce the formation of whorls of
      tightly packed membrane resembling myelin within the apical surface lesions to
      any great extent. Apical-surface changes induced by dihydrostreptomycin and
      amikacin are simply large distensions of the cell filled with cytoplasmic
      organelles of normal appearance. Although the effects of the aminoglycoside
      antibiotics are largely limited to the apical surface of the cell, poly-L-lysine
      induces complete necrosis of the cell, and spermine causes a dramatic increase in
      cytoplasmic electron density and condensation of the nuclear chromatin.

PMID- 7514589
TI  - The RNA chain elongation rate in Escherichia coli depends on the growth rate.
AB  - We determined the rates of mRNA and protein chain elongation on the lacZ gene
      during exponential growth on different carbon sources. The RNA chain elongation
      rate was calculated from measurements of the time elapsing between induction of
      lacZ expression and detection of specific hybridization with a probe near the 3'
      end of the mRNA. The elongation rate for the transcripts decreased 40% when the
      growth rate decreased by a factor of 4, and it always correlated with the rate of
      translation elongation. A similar growth rate dependency was seen for
      transcription on the infB gene and on a part of the rrnB gene fused to a
      synthetic, inducible promoter. However, the untranslated RNA chain specified by
      the rrnB gene was elongated nearly twice as fast as the two mRNA species encoded
      by infB and lacZ.

PMID- 7514590
TI  - Tn5401, a new class II transposable element from Bacillus thuringiensis.
AB  - A new class II (Tn3-like) transposable element, designated Tn5401, was recovered
      from a sporulation-deficient variant of Bacillus thuringiensis subsp. morrisoni
      EG2158 following its insertion into a recombinant plasmid. Sequence analysis of
      the insert revealed a 4,837-bp transposon with two large open reading frames, in
      the same orientation, encoding proteins of 36 kDa (306 residues) and 116 kDa
      (1,005 residues) and 53-bp terminal inverted repeats. The deduced amino acid
      sequence for the 36-kDa protein shows 24% sequence identity with the TnpI
      recombinase of the B. thuringiensis transposon Tn4430, a member of the phage
      integrase family of site-specific recombinases. The deduced amino acid sequence
      for the 116-kDa protein shows 42% sequence identity with the transposase of Tn3
      but only 28% identity with the TnpA transposase of Tn4430. Two small open reading
      frames of unknown function, designated orf1 (85 residues) and orf2 (74 residues),
      were also identified. Southern blot analysis indicated that Tn5401, in contrast
      to Tn4430, is not commonly found among different subspecies of B. thuringiensis
      and is not typically associated with known insecticidal crystal protein genes.
      Transposition was studied with B. thuringiensis by using plasmid pEG922, a
      temperature-sensitive shuttle vector containing Tn5401. Tn5401 transposed to both
      chromosomal and plasmid target sites but displayed an apparent preference for
      plasmid sites. Transposition was replicative and resulted in the generation of a
      5-bp duplication at the target site. Transcriptional start sites within Tn5401
      were mapped by primer extension analysis. Two promoters, designated PL and PR,
      direct the transcription of orf1-orf2 and tnpI-tnpA, respectively, and are
      negatively regulated by TnpI. Sequence comparison of the promoter regions of
      Tn5401 and Tn4430 suggests that the conserved sequence element ATGTCCRCTAAY
      mediates TnpI binding and cointegrate resolution. The same element is contained
      within the 53-bp terminal inverted repeats, thus accounting for their unusual
      lengths and suggesting an additional role for TnpI in regulating Tn5401
      transposition.

PMID- 7514586
TI  - Characterization of a taxol-resistant human small-cell lung cancer cell line.
AB  - Taxol is a novel anticancer agent with activity against a broad range of tumors.
      It has a unique ability to stabilize polymerized tubulin into microtubule bundles
      within the cell. We have established a taxol-resistant human small-cell lung
      cancer cell line (H69/Txl) by exposing H69 cells to stepwise increases in taxol
      concentration. The resistance of H69/Txl cells to taxol was 4.7-fold that of the
      original H69 cells: the IC50 values for H69 and H69/Txl were 113.7 +/- 56.54 nM
      and 538.7 +/- 214.7 nM by the tetrazolium dye assay, respectively. Removal of the
      drug from the medium resulted in a 38% decrease in the growth rate of H69/Txl as
      compared with that in the presence of 30 nM taxol, suggesting that the growth of
      H69/Txl was partially dependent on taxol. H69/Txl showed higher sensitivity to
      vinca alkaloids such as vindesine, vincristine and vinblastine than the parental
      H69. There was no significant difference in intracellular [3H]taxol content
      between H69 and H69/Txl cells. No MDR-1 mRNA was detected in H69/Txl by the
      reverse transcription polymerase chain reaction. There was no significant
      difference of total and polymerized tubulin content between H69 and H69/Txl
      cells. Altered mobility of one of the alpha-tubulin isoforms in H69/Txl was
      revealed by using isoelectric focusing and Western blotting with anti-alpha
      tubulin antibody. In H69, two alpha-tubulin isoforms were observed, whereas three
      were evident in H69/Txl, two of them comigrating with the isoforms of H69 and the
      other being more acidic. We observed the increased acetylation of alpha-tubulin
      in H69/Txl cells as compared with that in H69 cells. The acetylation of alpha
      tubulin may be responsible for the taxol resistance and/or taxol-dependent growth
      of H69/Txl.

PMID- 7514591
TI  - Role of the rfe gene in the synthesis of the O8 antigen in Escherichia coli K-12.
AB  - The Escherichia coli O8 antigen is a mannan composed of the trisaccharide repeat
      unit -->3)-alpha-Man-(1-->2)-alpha-Man-(1-->2)-alpha-Man-(1--> (K. Reske and K.
      Jann, Eur. J. Biochem. 67:53-56, 1972), and synthesis of the O8 antigen is rfe
      dependent (G. Schmidt, H. Mayer, and P. H. Makela, J. Bacteriol. 127:755-762,
      1976). The rfe gene has recently been identified as encoding a tunicamycin
      sensitive UDP-GlcNAc:undecaprenylphosphate GlcNAc-1-phosphate transferase (U.
      Meier-Dieter, K. Barr, R. Starman, L. Hatch, and P. D. Rick, J. Biol. Chem.
      267:746-753, 1992). However, the role of rfe in O8 side chain synthesis is not
      understood. Thus, the role of the rfe gene in the synthesis of the O8 antigen was
      investigated in an rfbO8+ (rfb genes encoding O8 antigen) derivative of E. coli K
      12 mutant possessing a defective phosphoglucose isomerase (pgi). The in vivo
      synthesis of O8 side chains was inhibited by the antibiotic tunicamycin. In
      addition, putative lipid carrier-linked O8 side chains accumulated in vivo when
      lipopolysaccharide outer core synthesis was precluded by growing cells in the
      absence of exogenously supplied glucose. The lipid carrier-linked O8 antigen was
      extracted from cells and treated with mild acid in order to release free O8 side
      chains. The water-soluble O8 side chains were then purified by affinity
      chromatography using Sepharose-bound concanavalin A. Characterization of the
      affinity-purified O8 side chains revealed the occurrence of glucosamine in the
      reducing terminal position of the polysaccharide chains. The data presented
      suggest that GlcNAc-pyrophosphorylundecaprenol functions as the acceptor of
      mannose residues for the in vivo synthesis of O8 side chains in E. coli K-12.

PMID- 7514592
TI  - Regulation of biosynthesis of nitric oxide.

PMID- 7514593
TI  - Altered body composition and increased frequency of diverse malignancies in
      insulin-like growth factor-II transgenic mice.
AB  - The physiological role of insulin-like growth factor (IGF) II (IGF-II) in adult
      humans is poorly understood. Rather high levels of IGF-II persist in adult human
      serum, whereas, in rodents, IGF-II levels are very low. To investigate the
      physiological and carcinogenic effects of persistently elevated IGF-II in adults,
      we have produced two lines of transgenic mice in which high levels of IGF-II (20-
      or 30-fold increase above normal) are persistently maintained in the blood. The
      transgene is driven by the major urinary protein promoter, and it is highly
      expressed in the liver and perputial glands in both lines. The adult transgenic
      mice are smaller than controls, and their body composition is altered. Their lean
      body mass is reduced by 5-8%, whereas fat mass is reduced between 44 and 77%. The
      mice expressing the highest level of IGF-II (30x) develop hypoglycemia and
      hypoinsulinemia and IGF-I levels are normal. Mice in the lower expression line
      (20-fold elevated IGF-II) develop hypoglycemia progressively over their lifetime.
      Mice from both lines also develop a diverse spectrum of tumors at a higher
      frequency than controls after 18 months of age, and the most frequent types of
      tumors are hepatocellular carcinomas and lymphomas. Squamous cell carcinoma,
      sarcoma, and thyroid carcinomas also occurred in our test group. The long latent
      period before tumors arise and the wide spectrum of tumor types suggest that IGF
      II may function primarily as a tumor progression factor in mice via autocrine and
      endocrine mechanisms of action.

PMID- 7514595
TI  - The pteridine binding site of brain nitric oxide synthase. Tetrahydrobiopterin
      binding kinetics, specificity, and allosteric interaction with the substrate
      domain.
AB  - Nitric oxide (NO) synthases contain FAD, FMN, heme, and (6R)-5,6,7,8-tetrahydro-L
      biopterin as prosthetic groups. We have characterized the pteridine-binding site
      of purified brain NO synthase, using 3H-labeled (6R)-5,6,7,8-tetrahydro-L
      biopterin as radioligand. Association of [3H]tetrahydrobiopterin followed second
      order kinetics (kon = 1.3 x 10(6) M-1 min-1), the dissociation reaction was
      reversible and first-order (koff = 3.2 x 10(-1) min-1), yielding a kinetic KD of
      0.25 microM. Binding of the radioligand was competitively antagonized by several
      pteridine derivatives with the following order of potency (KI): 7,8-dihydro-L
      biopterin (2.2 microM), (6S)-5,6,7,8-tetrahydro-L-biopterin (19 microM), (6R,S)-6
      methyl-5,6,7,8-tetrahydropterin (240 microM), and 6,7-dimethyl-5,6,7,8
      tetrahydropterin (> 1 mM). The affinity of NO synthase for tetrahydrobiopterin
      was increased 6-fold in the presence of 0.1 mM L-arginine (KD = 37 nM), and,
      conversely, tetrahydrobiopterin enhanced the affinity of the enzyme for 3H
      labeled NG-nitro-L-arginine about 2-fold. 7-Nitroindazole, which presumably binds
      to the heme group of NO synthase, competitively inhibited binding of
      [3H]tetrahydrobiopterin and [3H]NG-nitro-L-arginine with similar Ki values (0.1
      microM). Functional as well as binding studies revealed that 7-nitroindazole was
      competitive with both L-arginine and tetrahydrobiopterin. Our data indicate that
      brain NO synthase exhibits a highly specific binding site for (6R)-5,6,7,8
      tetrahydro-L-biopterin, which allosterically interacts with the substrate domain
      and may be located proximal to the prosthetic heme group of NO synthase.

PMID- 7514594
TI  - Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid
      dioxygenase.
AB  - Increased cerebral levels of the endogenous excitotoxin quinolinic acid (QUIN)
      have been speculatively linked to neuronal damage following neurological and
      inflammatory disorders. 3-Hydroxyanthranilic-acid dioxygenase (3-HAO; 3
      hydroxyanthranilate 3,4-dioxygenase, EC 1.13.11.6) is the enzyme that catalyzes
      the synthesis of QUIN from 3-hydroxyanthranilic acid, and evidence suggests that
      it could play a role in disorders associated with altered tissue levels of QUIN.
      In this report, we describe the isolation of a full-length cDNA clone encoding
      human 3-HAO (h3-HAO). Degenerate oligonucleotides were designed from the amino
      acid sequences of tryptic peptides of rat liver 3-HAO, and they were used as
      primers for reverse transcription-polymerase chain reaction of rat liver RNA. The
      resulting rat cDNA product was used to screen a human hepatoma cell line (HepG2)
      cDNA library and to isolate a human 3-HAO cDNA clone. This clone was found to
      have an insert of 1276 nucleotides. The deduced primary structure of h3-HAO is
      composed of 286 amino acid residues with a predicted molecular mass of
      approximately 32.6 kDa. The human sequence exhibits high similarity (94%) to the
      rat partial amino acid sequence deduced from the rat reverse transcription
      polymerase chain reaction fragment. Insertion of the h3-HAO coding sequence into
      a eukaryotic expression vector yielded relatively high amounts of the active
      enzyme in human embryonic kidney HEK-293 cells. The Km value of 3-HANA for
      recombinant h3-HAO (approximately 2 microM) was in good agreement with that
      reported for the native enzyme. Immunoblot analysis of recombinant h3-HAO
      revealed a polypeptide with an apparent molecular mass of 32 kDa, as predicted
      from the deduced amino acid sequence. RNA blot analysis of human liver and HepG2
      cells revealed one major species of h3-HAO mRNA of approximately 1.3 kilobases.

PMID- 7514596
TI  - Thrombin receptor-activating peptides differentially stimulate platelet-derived
      growth factor production, monocytic cell adhesion, and E-selectin expression in
      human umbilical vein endothelial cells.
AB  - Recent studies have shown that the synthetic peptides SFL LRN and SFL LRN PND
      KYEPF (thrombin receptor-activating peptides (TRAP)) derived from the deduced
      sequence of the new amino terminus of the cleaved thrombin receptor can mimic
      thrombin receptor activation, act as full agonists for platelet activation, and
      induce prostaglandin I2 production as well as cytosolic Ca2+ increase in human
      umbilical vein endothelial cells (HUVEC). Here, we have compared the ability of
      these synthetic peptide ligands and thrombin to stimulate platelet-derived growth
      factor (PDGF) production by, and monocyte adhesion to, HUVEC. Thrombin (50
      units/ml) and TRAP (25 microM) maximally stimulated monocyte adhesion.
      Furthermore, the stimulation of E-selectin cell surface expression and the steady
      state E-selectin mRNA levels by thrombin and TRAP were comparable. Thrombin (50
      units/ml) stimulated PDGF production 400% above the basal level in 24 h, whereas
      the 6-mer and 14-mer TRAP, even at 200 microM, did not significantly stimulate
      PDGF production. Northern analysis, however, revealed that TRAP at 100 microM
      stimulated PDGF-A and -B chain mRNA expression to a level similar to that induced
      by thrombin. These results suggest that activation of cell signaling by TRAP can
      mimic thrombin and is sufficient for the stimulation of monocyte adhesion to
      HUVEC; however, thrombin-stimulated PDGF production by HUVEC may require
      mechanisms in addition to the signaling events initiated by TRAP or may require
      the participation of a novel thrombin receptor.

PMID- 7514597
TI  - Differential activation of cation channels and non-selective pores by macrophage
      P2z purinergic receptors expressed in Xenopus oocytes.
AB  - In macrophages and certain other cell types, extracellular ATP4- can increase
      plasma membrane permeability through activation of the P2z purinergic receptor.
      This permeability change involves the induction of non-selective pores which are
      permeable to molecules with M(r) < or = 900. Electrophysiological studies
      indicate that agonist occupation of P2z purinergic receptors can additionally
      activate cation channels which may be distinct from the non-selective pores. We
      have observed that mammalian P2z purinergic receptors can be expressed in Xenopus
      oocytes injected with mRNA from the BAC1.2F5 murine macrophage cell line. Under
      voltage-clamp analysis, these oocytes exhibit a multiphasic inward current in
      response to ATP or 3'-O-(4-benzoyl)-benzoyl-ATP (BzATP), a selective agonist for
      the P2z purinergic receptor. This ATP/BzATP-induced current is characterized by a
      rapidly activated phase which is followed by a delayed, but steady, increase in
      conductance. We have used two-electrode voltage-clamp analysis and ion
      substitution to further characterize these P2z purinergic receptor-induced
      currents as expressed in mRNA-injected oocytes. N,N-Hexamethylene amiloride
      (HMA), a potent inhibitor of various exchangers and channels, selectively and
      reversibly inhibited the delayed component of the BzATP-induced inward current.
      This delayed HMA-sensitive current can be carried by large organic cations, such
      as N-methyl-D-glucamine (NMG+) and Tris+, in addition to small inorganic cations
      including Na+, Li+, and K+. In contrast, the rapidly activated HMA-insensitive
      current is readily carried by Na+, Li+, and K+, but is poorly carried by NMG+ and
      Tris+. Additional studies characterized P2z receptor regulation of Ca2+ influx,
      depolarization, ethidium uptake, and fura-2 loss in native BAC1.2F5 macrophages.
      Reduced temperature permitted discrimination of two distinct permeability
      pathways which could be activated by BzATP. At 20 degrees C, BzATP did not
      significantly increase membrane permeability to NMG+ (M(r) 195), ethidium+ (M(r)
      314), or fura-2 (M(r) 831) but did stimulate an ion conducting pathway which
      could be competitively permeated by Na+ or Ca2+. At 37 degrees C, BzATP treatment
      increased membrane permeability to NMG+, ethidium+, and fura-2, in addition to
      Na+ and Ca2+. These data indicate that macrophage P2z purinergic receptors can be
      differentially coupled to: 1) a rapidly gated cation channel, and 2) a time- and
      temperature-dependent formation of non-selective pores. These two permeability
      pathways can be distinguished by their rates of activation, ion selectivities,
      sensitivities to amiloride analogs, and temperature dependence.

PMID- 7514598
TI  - Macrophage-stimulating protein inhibits induction of nitric oxide production by
      endotoxin- or cytokine-stimulated mouse macrophages.
AB  - Human serum macrophage-stimulating protein (MSP) is a disulfide-linked
      heterodimer that induces motile and phagocytic activity of mouse resident
      peritoneal macrophages. In this work, we found that MSP blocked the increase in
      macrophage nitric oxide synthase mRNA, as well as the associated increase in
      nitric oxide production, that occurred in response to several stimuli. These
      included bacterial products and mammalian cytokines: endotoxin, and interferon
      gamma plus endotoxin, interleukin-2, or tumor necrosis factor-alpha. The
      inhibition by MSP of induction of nitric oxide synthase mRNA and nitric oxide
      secretion was concentration-dependent. The concentration of MSP that caused
      maximal inhibition of nitric oxide production was comparable with the optimum for
      stimulation of macrophage motile and phagocytic activity. Time course studies
      showed that nitrite was first detected in culture fluid about 8 h after endotoxin
      stimulation, and it accumulated at a linear rate during the ensuing 16 h.
      Inhibition by MSP occurred during the 8-h lipopolysaccharide (LPS) induction
      period; inhibition was maximal when MSP and LPS were added together and decreased
      progressively to no inhibition as the interval between LPS and MSP addition
      increased to 11 h.

PMID- 7514599
TI  - STV1 gene encodes functional homologue of 95-kDa yeast vacuolar H(+)-ATPase
      subunit Vph1p.
AB  - The Saccharomyces cerevisiae gene, VPH1 (Vacuolar pH 1), encodes a 95-kDa
      integral membrane subunit of the vacuolar-type H(+)-ATPase (V-ATPase) that is
      required for enzyme assembly; disruption of the VPH1 gene impairs vacuolar
      acidification (Manolson, M.F., Proteau, D., Preston, R. A., Stenbit, A., Roberts,
      B. T., Hoyt, M. A., Preuss, D., Mulholland, J., Botstein, D., and Jones, E. W.
      (1992) J. Biol. Chem. 267, 14294-14303). Here we show that STV1 (Similar To VPH1)
      encodes an integral membrane polypeptide of 102 kDa with 54% identity with the
      peptide sequence of Vph1p. High copy expression of STV1 partially restores
      vacuolar acidification in a delta vph1 mutant strain; solubilization and
      fractionation of membrane proteins from these vacuoles show that Stv1p co
      purifies with bafilomycin A1-sensitive ATPase activity and with the 60- and 69
      kDa V-ATPase subunits. Immunofluorescence microscopy of strains bearing a single
      copy of epitope-tagged STV1 reveals punctate staining of the cytoplasm;
      overexpression of epitope-tagged Stv1p reveals both punctate cytoplasmic staining
      and vacuolar membrane staining. Northern analysis shows that disruption of STV1
      does not affect the level of transcription of VPH1 and that disruption of VPH1
      does not affect the level of transcription of STV1. Strains bearing disruption of
      genes encoding other V-ATPase subunits (VMA1, VMA2, VMA3, and VMA4) fail to grow
      on media supplemented with 100 mM CaCl2 or 4 mM ZnCl2, media buffered to pH 7.5,
      or media with a glycerol carbon source. On the same types of media only a delta
      vph1 delta stv1 double disruption mutant has growth phenotypes equivalent to
      strains bearing a single disruption of the VMA1, VMA2, VMA3, and VMA4 genes; a
      delta vph1 strain has only moderate growth inhibition while a delta stv1 strain
      has wild type growth on the conditions listed above. We conclude that Stv1p is a
      functional homologue of Vph1p and suggest that Stv1p and Vph1p may be equivalent
      subunits for V-ATPases located on different organelles. The function of these 100
      kDa homologues may be to target or regulate other common V-ATPase subunits for
      two distinct cellular locations.

PMID- 7514600
TI  - Insulin-like growth factors, their binding proteins, and transforming growth
      factor-beta 1 in oxidant-arrested lung alveolar epithelial cells.
AB  - The epithelium of the pulmonary alveolus is a major target for oxidant injury,
      and its proper repair following injury is dependent on the proliferative response
      of its stem cells, the type 2 cells. We have recently shown that hyperoxia
      arrests proliferation of an immortalized type 2 cell line (SV40T-T2) and that
      expression of several growth-related genes, normally induced near the G1/S and
      boundary was altered with a block of translation of their mRNA. In the present
      study we examined the possible role of the insulin-like growth factor (IGF)
      system and of transforming growth factor-beta 1 (TGF-beta 1) in the arrest of
      proliferation induced by hyperoxia. We show that IGF-binding protein 2 (IGFBP-2)
      accumulates to higher levels in culture medium of SV40T-T2 cells whose
      proliferation has been arrested by hyperoxia. This proliferation arrest is
      associated with increased expression of IGFBP-2 mRNA and with induction of type 2
      IGF receptor and IGF-II mRNAs. When O2-arrested cells were allowed to resume
      proliferation in normoxia, the level of expression of these genes rapidly
      decreased to control levels. We also, found that TGF-beta 1 was induced by O2
      exposure, that TGF-beta 1 inhibited SV40T-T2 proliferation, and that TGF-beta 1
      itself was a potent stimulator of IGFBP-2 expression. These studies suggest a
      regulatory link between components of the IGF system and TGF-beta 1 in hyperoxic
      control of cell proliferation of alveolar epithelial cells.

PMID- 7514601
TI  - Intrinsic molecular activities of the interferon-induced 2-5A-dependent RNase.
AB  - 2-5A-dependent RNase (RNase L), a unique endoribonuclease that requires 5'
      phosphorylated 2',5'-linked oligoadenylates (2-5A), functions in the molecular
      mechanism of interferon action. Because this enzyme is present at very low levels
      in nature, characterization and analysis have been limited. The molecular cloning
      of human, 2-5A-dependent RNase cDNA has facilitated its expression to high levels
      in insect cells by infecting with recombinant baculovirus. To determine the
      properties of the enzyme in the absence of other proteins, the recombinant 2-5A
      dependent RNase was purified to homogeneity. The purified enzyme migrated as a
      monomer upon gel filtration in the absence of activator and showed highly
      specific, 2-5A-dependent RNase activity. The precise activator requirements were
      determined by stimulating the purified enzyme with a variety of 2',5'-linked
      oligonucleotides. The activated enzyme was capable of cleaving poly(rU) and, to a
      lesser extent, poly(rA), to sets of discrete products ranging from between 4 and
      22 nucleotides in length. Reduced rates of 2-5A-dependent RNA cleavage were
      observed even after removal of ATP and chelation of divalent cations. However,
      optimal RNA cleavage rates required the presence of either manganese or magnesium
      and ATP.

PMID- 7514602
TI  - Mapping of the immunophilin-immunosuppressant site of interaction on calcineurin.
AB  - The interaction of the immunosuppressive complexes cyclosporin A-cyclophilin A
      and FK506 binding protein-FK506 with the Ca(2+)- and calmodulin-dependent protein
      phosphatase calcineurin has been investigated by means of photoaffinity labeling
      and chemical cross-linking. Photolabeling of purified bovine brain calcineurin
      with the affinity label [O-[4-[4-(1-diazo-2,2,2
      trifluoroethyl)benzoyl]aminobutanoyl]-D- serine8]cyclosporin in the presence of
      cyclophilin A results, in addition to the labeling of cyclophilin itself, in the
      transfer of some of the chemical probe to both the catalytic subunit A and the
      regulatory subunit B of calcineurin. Chemical cross-linking studies with
      disuccinimidyl suberate in the presence of either cyclophilin A, B, or C in
      complex with cyclosporin A or FK506 binding protein-FK506 result on the other
      hand in the apparently exclusive and strictly immunosuppressant-dependent
      formation of covalent immunophilin-calcineurin B subunit products. Cross-linking
      of immunophilins to calcineurin B subunit requires the presence of subunit A. In
      the present study, using a set of recombinant maltose-binding protein fusion
      products representing different stretches of the catalytic subunit A, we were
      able to map the minimal calcineurin A sequence necessary for immunophilin-ligand
      calcineurin B interaction to occur.

PMID- 7514603
TI  - Phosphorylation of Gi alpha 2 attenuates inhibitory adenylyl cyclase in
      neuroblastoma/glioma hybrid (NG-108-15) cells.
AB  - Cross-regulation from the stimulatory phospholipase C to the adenylyl cyclase
      pathways was explored in neuroblastoma-glioma NG-108-15 cells in culture.
      Activation of protein kinase C by phorbol myristic acid resulted in a markedly
      attenuated activation of the inhibitory adenylyl cyclase response to delta-opiate
      agonists and epinephrine but not to the muscarinic agonist carbachol. The ability
      of okadaic acid to mimic the effects of phorbol myristic acid on the inhibitory
      response suggested a role for protein phosphorylation. Adenylyl cyclase activity
      from cells in which protein kinase C had been activated demonstrated a loss in
      the inhibitory adenylyl cyclase response at the level of the G-protein.
      Activation of protein kinase C prompted a 2-4-fold increase in phosphorylation of
      G1 alpha 2 in cells metabolically labeled with [32P]orthophosphate. The phosphate
      content of Gi alpha 2 was determined to be approximately 0.5 mol/mol subunit in
      the unstimulated cells and approximately 1.5 mol/mol subunit for cells in which
      protein kinase C was activated. The effects of okadaic acid, 4-alpha-phorbol, and
      calphostin C on inhibition of adenylyl cyclase in cells treated with phorbol
      myristic acid correlate with the effects of these agents on phosphorylation of Gi
      alpha 2. The time courses for attenuation of inhibitory adenylyl cyclase and that
      for phosphorylation of Gi alpha 2 were similar in cells challenged with phorbol
      myristic acid. These data argue for cross-regulation from the stimulatory protein
      kinase C to inhibitory adenylyl cyclase pathways at the level of Gi alpha 2 via
      protein phosphorylation.

PMID- 7514604
TI  - Enhancement of MHC-unrestricted cytotoxic activity of human CD56+ CD3- natural
      killer (NK) cells and CD3+ T cells by rhamnogalacturonan: target cell specificity
      and activity against NK-insensitive targets.
AB  - Rhamnogalacturonan-mediated enhancement of MHC-unrestricted cytotoxicity was
      studied with freshly isolated CD56+CD3- natural killer (NK) cells, interleukin-2
      (IL-2)-activated CD56+ lymphokine-activated killer (LAK) cells und IL-2/anti-CD3
      activated T cells as effector cells using NK-sensitive and NK-insensitive tumor
      cells as targets. The rhamnogalacturonan fractions IM, IP, and IQ were prepared
      from commercially available extracts of Viscum album. The dose/response relation
      of IM, IP, and IQ demonstrated the presence of various concentrations of
      cytotoxicity-enhancing compounds in all three fractions that were identified as
      rhamnogalacturonans by degradation studies with poly-alpha-D-galacturonidase (EC
      3.2.1.15) and alpha-1,6-rhamnosidase (EC 3.2.1.40). Specific cytotoxicity of all
      three effector cell populations as well as the respective rhamnoagalacturonan
      mediated cytotoxicity enhancement was readily inhibited in a dose-dependent
      manner by 60%-deacetylated mannose pentaacetate. Rhamnogalacturonan-mediated
      enhancement of cytotoxicity of fresh CD56+ NK cells was also observed with four
      of five NK-insensitive tumor cells as targets, indicating that the effector
      cell/tumor-cell bridging activity of rhamnogalacturonans renders NK-insensitive
      targets susceptible to NK-mediated lysis. Moreover, the rhamnogalacturonan
      mediated cytotoxicity enhancement became even more prominent when lymphokine
      activated CD56+ LAK and CD3+ T cells were assayed with the NK-insensitive tumor
      cell targets.

PMID- 7514605
TI  - Biogenesis and transmembrane topology of the CHIP28 water channel at the
      endoplasmic reticulum.
AB  - CHIP28 is a 28-kD hydrophobic integral membrane protein that functions as a water
      channel in erythrocytes and renal tubule epithelial cell membranes. We examined
      the transmembrane topology of CHIP28 in the ER by engineering a reporter of
      translocation (derived from bovine prolactin) into nine sequential sites in the
      CHIP28 coding region. The resulting chimeras were expressed in Xenopus oocytes,
      and the topology of the reporter with respect to the ER membrane was determined
      by protease sensitivity. We found that although hydropathy analysis predicted up
      to seven potential transmembrane regions, CHIP28 spanned the membrane only four
      times. Two putative transmembrane helices, residues 52-68 and 143-157, reside on
      the lumenal and cytosolic surfaces of the ER membrane, respectively. Topology
      derived from these chimeric proteins was supported by cell-free translation of
      five truncated CHIP28 cDNAs, by N-linked glycosylation at an engineered consensus
      site in native CHIP28 (residue His69), and by epitope tagging of the CHIP28 amino
      terminus. Defined protein chimeras were used to identify internal sequences that
      direct events of CHIP28 topogenesis. A signal sequence located within the first
      52 residues initiated nascent chain translocation into the ER lumen. A stop
      transfer sequence located in the hydrophobic region from residues 90-120
      terminated ongoing translocation. A second internal signal sequence, residues 155
      186, reinitiated translocation of a COOH-terminal domain (residues 186-210) into
      the ER lumen. Integration of the nascent chain into the ER membrane occurred
      after synthesis of 107 residues and required the presence of two membrane
      spanning regions. From this data, we propose a structural model for CHIP28 at the
      ER membrane in which four membrane-spanning alpha-helices form a central aqueous
      channel through the lipid bilayer and create a pathway for water transport.

PMID- 7514606
TI  - Role of muscle insulin-like growth factors in nerve sprouting: suppression of
      terminal sprouting in paralyzed muscle by IGF-binding protein 4.
AB  - The protracted absence of muscle activation initiates complex cellular and
      molecular reactions aimed at restoring functional neuromuscular transmission and
      preventing degenerative processes. A central aspect of these reactions is the
      sprouting of intramuscular nerves in the vicinity of inactivated muscle fibers.
      Sprouts emerging from terminal nerve branches and nodes of Ranvier can
      reestablish functional contacts with inactive muscle fibers, and this is an
      essential restorative process in pathological conditions of the neuromuscular
      system. Due to their rapid upregulation in inactive skeletal muscle fibers and
      their ability to induce nerve sprouting in adult muscle, insulin-like growth
      factors (IGFs) are candidate signaling molecules to promote restorative reactions
      in the neuromuscular system. In this study we have exploited the high affinity
      and specificity of IGF-binding protein 4 (IGF-BP4) and IGF-BP5 for IGF1 and IGF2
      to determine whether these growth factors are involved in the nerve sprouting
      reaction in paralyzed skeletal muscle. In tissue culture experiments with sensory
      and motoneurons we demonstrate that the neurite promoting activity of IGF1 is
      blocked by IGF-BP4, and that a similar IGF-BP-sensitive activity is detected in
      muscle extracts from paralyzed, but not from control muscle. In in vivo
      experiments, we show that local delivery of IGF-BP4 to Botulinum toxin A
      paralyzed skeletal muscle effectively prevents nerve sprouting in that muscle.
      Our findings indicate that muscle IGFs play an essential role in intramuscular
      nerve sprouting. In addition, these findings suggest that IGFs are major
      signaling factors from inactivated muscle to promote local restorative reactions,
      including interstitial cell proliferation and nerve sprouting.

PMID- 7514607
TI  - PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF
      beta-receptors.
AB  - To delineate potential angiogenic roles of platelet-derived growth factor (PDGF),
      we have investigated PDGF and its receptors on bovine aortic endothelial cells
      that exhibit spontaneous angiogenesis in vitro (angiogenic endothelial cells).
      Initiation of cord/tube formation by angiogenic endothelial cells required bovine
      or human serum. Neutralization of PDGF-BB in human serum with a monoclonal anti
      PDGF-BB antibody reduced cord/tube formation by 37 +/- 10%, whereas neutralizing
      anti-PDGF-AA and an IgG isotype-matched control antibody had no effect. DNA
      synthesis in response to PDGF-BB increased as the cords and tubes developed;
      furthermore, PDGF-BB induced the incorporation of BrdU in the nuclei of cells
      associated with these structures. PDGF beta-receptor (PDGF-beta) mRNA increased
      concomitantly with cord/tube formation, and PDGFR-beta were specifically
      localized by immunocytochemistry to developing and mature cords and tubes.
      However, PDGFR-beta transcripts and protein were undetectable in nonangiogenic
      endothelial cells, and PDGF alpha-receptor mRNA was not expressed in either
      endothelial cell strain. In contrast to nonangiogenic endothelial cells,
      angiogenic endothelial cells did not express the PDGF B-chain, the required
      ligand for the PDGFR-beta. We conclude that (a) PDGF-BB can contribute to
      angiogenesis in vitro, (b) PDGFR-beta are specific for cord/tube-forming
      endothelial cells and mediate endothelial proliferation and cord/tube formation,
      and (c) in angiogenic and nonangiogenic endothelial cells, the expression of
      PDGFR-beta and PDGF B-chain is inversely correlated. We therefore suggest that
      paracrine PDGF might amplify angiogenesis via direct action on endothelially
      expressed PDGFR-beta.

PMID- 7514609
TI  - Enhancement of differentiation induction of mouse myelomonocytic leukemic cells
      by extracellular ATP.
AB  - We examined the effect of ATP on the terminal differentiation of mouse
      myelomonocytic leukemic M1 cells to macrophages. Although ATP alone did not
      induce M1 cell differentiation, addition of ATP with the differentiation inducer,
      interleukin 6 (IL-6), enhanced the induction of differentiation by IL-6 about two
      fold. Comparison among several adenine nucleotides revealed that the order of
      effectiveness on differentiation enhancement was ATP > ADP > AMP > or =
      adenosine. Using reactive blue 2, a P2 receptor antagonist, we confirmed that the
      effect of ATP on the stimulation of differentiation was mediated through the P2
      purinergic receptor. Examination of cytosolic [Ca2+] elevation by ATP and
      comparison of potency of differentiation enhancement among several ATP analogs
      demonstrated that the effect of differentiation enhancement was mediated through
      P2y purinergic receptors expressed on M1 cell surface. Within 3 h of exposure,
      ATP alone slightly increased the expression of differentiation-related immediate
      early response genes, c-myc and JunB, and ATP also enhanced the IL-6-induced
      expression of these genes. Induction of JunB expression by ATP analogs correlated
      with their potency of differentiation enhancement, which suggested that induction
      of JunB by ATP is one of signaling pathways involved in the exertion of its
      differentiation-enhancing effect.

PMID- 7514608
TI  - SPARC is a source of copper-binding peptides that stimulate angiogenesis.
AB  - SPARC is a transiently expressed extracellular matrix-binding protein that alters
      cell shape and regulates endothelial cell proliferation in vitro. In this study,
      we show that SPARC mRNA and protein are synthesized by endothelial cells during
      angiogenesis in vivo. SPARC and peptides derived from a cationic region of the
      protein (amino acids 113-130) stimulated the formation of endothelial cords in
      vitro; moreover, these peptides stimulated angiogenesis in vivo. Mapping of the
      active domain demonstrated that the sequence KGHK was responsible for most of the
      angiogenic activity; substitution of the His residue decreased the effect. We
      found that proteolysis of SPARC provided a source of KGHK, GHK, and longer
      peptides that contained these sequences. Although the Cu(2+)-GHK complex had been
      identified as a mitogen/morphogen in normal human plasma, we found KGHK and
      longer peptides to be potent stimulators of angiogenesis. SPARC113-130 and KGHK
      were shown to bind Cu2+ with high affinity; however, previous incubation with
      Cu2+ was not required for the stimulatory activity. Since a peptide from a second
      cationic region of SPARC (SPARC54-73) also bound Cu2+ but had no effect on
      angiogenesis, the angiogenic activity appeared to be sequence specific and
      independent of bound Cu2+. Thus, specific degradation of SPARC, a matrix
      associated protein expressed by endothelial cells during vascular remodeling,
      releases a bioactive peptide or peptides, containing the sequence (K)GHK, that
      could regulate angiogenesis in vivo.

PMID- 7514610
TI  - Responses of salivary acinar cells to intracellular alkalinization.
AB  - Responses of rat submandibular acini to intracellular alkalinization were
      investigated. Intracellular alkalinization was induced by addition of NH4Cl or
      methyl amines, or by prepulse with Na butyrate. Only partial recovery occurred
      following Na butyrate prepulse or methylated amine addition, but full recovery
      was observed following addition of NH4Cl. The latter recovery was DIDS and
      dimethylamiloride-insensitive but was inhibited by bumetanide or high [K+] and
      stimulated in Na(+)-free buffer and by ouabain. Acetylcholine stimulated recovery
      from NH4Cl- or Na butyrate pre-pulse-induced alkalinization and reduced the
      extent of alkalinization induced by methylated amines. Acetylcholine-stimulated
      recovery from NH4Cl-induced alkalinization was mimicked by substance P or
      ionomycin and was partially Ca(2+)-dependent. This stimulated recovery was
      bumetanide-insensitive but was partially sensitive to charybdotoxin. Taken
      together, these data indicate that in unstimulated cells, recovery from
      alkalinization induced by NH4Cl occurs by bumetanide-sensitive transport of the
      NH4+ ion, that DIDS-inhibitable anion transport contributes little to this
      recovery, and that acetylcholine and other Ca(2+)-elevating agents accelerate
      recovery from NH4Cl-induced alkaline challenge by a mechanism insensitive to
      bumetanide, DIDS, ouabain, and dimethylamiloride but sensitive to extracellular
      Ca2+ and to charybdotoxin. Partial recovery from alkaline challenge can also
      occur in the absence of NH4+ ions, and acetylcholine also stimulates this mode of
      recovery. Together, these data suggest that these cells have little intrinsic
      ability to recover from intracellular alkalinization and that the NH4+ ion may be
      a surrogate for K+ in at least two ion transport pathways.

PMID- 7514611
TI  - Modulation of keratin 14 and alpha-fetoprotein expression during hepatic oval
      cell proliferation and liver regeneration.
AB  - Keratin 14 (K14) expression has recently been demonstrated in cell lines of non
      parenchymal hepatic origin (Bisgaard et al., 1993, Mol. Carcinog., 7:60-66;
      Bisgaard et al., 1991, J. Cell. Physiol., 147:333-343). These cell lines are
      thought to represent a progeny of a dormant stem cell compartment present in the
      adult rat liver, which may participate in the restoration of the liver mass after
      experimental liver injury. Utilizing a combination of 2-acetylaminofluorene (2
      AAF) administration and partial hepatectomy to activate liver regeneration by
      proliferation of oval cells, we examined the modulation of K14 as well as alpha
      fetoprotein (AFP) expression in proliferating oval cells and lineages
      hypothesized to be derived herefrom. We showed by Northern blot and in situ
      hybridization analyses that K14 and AFP transcripts were initially accumulating
      in epithelial cells located in subsets of ductal structures in the portal areas.
      As oval cells infiltrated the liver parenchyma, K14 transcripts were detected in
      oval cells, in foci of small basophilic hepatocytes, and in structures resembling
      glandular intestinal-type epithelium. AFP was expressed in oval cells, and at low
      but detectable levels in foci of basophilic hepatocytes, but not in glandular
      intestinal-type epithelium. Neither K14 nor AFP transcripts were detected in bile
      ducts or mature hepatocytes at any time during oval cell proliferation and
      reconstitution of the liver mass. To further study the modulation of K14 and AFP
      expression we utilized an in vitro model in which spontaneous transformation of
      rat liver epithelial (RLE) cells appeared to mimic the process of early
      differentiation along the hepatic lineage in vivo. We demonstrated that
      undifferentiated RLE cells at a late passage expressed K14 and vimentin, whereas
      transformation and differentiation to hepatoblast-like progeny resulted in an
      abrogation of K14 and vimentin expression and an induction of K18 and AFP. We
      propose that K14 and AFP are sequentially modulated in subpopulations of oval
      cells involved in the ongoing reconstitution of the liver mass.

PMID- 7514612
TI  - Phenotypic modulation of keratins, vimentin, and alpha-fetoprotein in cultured
      rat liver epithelial cells after chemical, oncogene, and spontaneous
      transformation.
AB  - Several lines of evidence have indicated that rat liver epithelial (RLE) cell
      lines may be related to a dormant stem cell compartment in the liver in vivo. We
      have demonstrated that keratin 14 (K14) is expressed together with vimentin in
      undifferentiated RLE cells. However, upon spontaneous transformation and
      differentiation to hepatoblast-like progeny the expression of these intermediate
      filaments (IF) is abrogated, while expression of another set of genes, among
      others keratin 18 (K18) and alpha-fetoprotein (AFP), is induced (Bisgaard et al.,
      1994, J. Cell. Physiol., in press). To better understand the mechanisms
      underlying IF expression during transformation and differentiation of RLE cells
      we examined the expression and regulation of IFs in clonal cell lines of
      chemically, oncogene, and spontaneously transformed RLE cells and their resulting
      tumors. These clonal lines provided a wide variety of tumor phenotypes including
      trabecular, solid and tubular adenocarcinomas, undifferentiated carcinomas, and
      spindle cell carcinomas. Northern blot analysis of the cell lines confirmed the
      differential expression of IF mRNAs. While keratin 8 (K8) was expressed at
      similar steady-state levels in all cell lines, K14 and vimentin but not K18 were
      expressed in the majority of cell lines chemically transformed with aflatoxin B1
      or by transduction of oncogenes. In contrast, cell lines transformed
      spontaneously by prolonged passage in vitro expressed K18, while K14 and vimentin
      were absent. The keratin expression pattern in vitro was retained in the majority
      of the resulting tumors. However, the keratins expressed in vitro did not
      accurately predict the tumor phenotype in vivo. In particular, in tumors typed
      morphologically as adenocarcinomas, the keratin pair typically expressed in
      chemically transformed tumor cells was K8/K14, whereas K8/K18 was expressed in
      the tumors derived from spontaneously transformed cell lines. Finally we showed
      by nuclear run-on and in vitro translation analyses that the expression of K14,
      K18, and vimentin in transformed RLE cell lines was regulated at the
      transcriptional level, whereas that of K8 appeared to be posttranslational. These
      findings suggest that events controlling the differential expression of IF genes
      are involved in the processes leading to transformation and differentiation of
      the RLE cell lines. We conclude that the transformed RLE cell lines provide a
      valuable model to further examine the regulatory mechanisms involved in hepatic
      differentiation of undifferentiated "progenitor-like" RLE cells.

PMID- 7514613
TI  - Tenascin induction in tenascin nonproducing carcinoma cell lines in vivo and by
      TGF-beta 1 in vitro.
AB  - Tenascin, a novel six-armed extracellular-matrix glycoprotein, is expressed in a
      temporally and spatially restricted pattern during carcinogenesis in association
      with stromal-epithelial interactions. In this study, we have tested the
      hypothesis that tenascin expression depends upon the change of the cellular
      environment from in vitro to in vivo. The distribution and alterations in the
      expression of tenascin were compared between in vitro and in vivo studies in a
      variety of human epithelial- and nonepithelial-derived cell lines. When cell
      lines were transplanted into nude mice, all xenografts induced host-mouse-stroma
      derived tenascin. Four carcinoma-derived cell lines and all sarcoma-derived
      lines, which secreted tenascin in vitro, were found to produce human tenascin
      after transplantation. Furthermore, three carcinoma-derived cell lines, A431, HEp
      2, and MCF7, which did not synthesize tenascin in vitro, did synthesize human
      tenascin after transplantation. These tenascin nonproducing carcinoma cell lines
      did not express tenascin mRNA in vitro. The addition of TGF-beta 1 to the culture
      medium induced the synthesis and secretion of tenascin, but TGF-beta 2 and bFGF
      were less effective. TGF-beta 1 also induced other extracellular-matrix
      components, fibronectin and laminin. TGF-beta 1 did not induce tenascin in
      tenascin nonproducing carcinoma cell lines, such as WiDr and A549, in which human
      tenascin was not induced after transplantation. We have established an in vitro
      system in which tenascin is induced by the diffusible factor TGF-beta 1. This
      system could shed light on the mechanism of induction of human tenascin observed
      in vivo in tenascin nonproducing carcinoma cell lines.

PMID- 7514614
TI  - Characterization of regulatory volume decrease in the THP-1 and HL-60 human
      myelocytic cell lines.
AB  - Exposure to hypotonic stress produces a transient increase in cell volume
      followed by a regulatory volume decrease (RVD) in both THP-1 and HL-60 cells. In
      contrast, cells exposed to hypotonic stress in a high K/low Na Hanks' solution
      not only failed to volume regulate, but displayed a secondary swelling. Thus,
      while an outward K gradient was required for RVD, the secondary swelling
      indicated that hypotonic stress increased permeability in the absence of a
      negative membrane potential. The K channel blocker quinine (1-4 mM) blocked RVD
      in both cell types. Gramicidin's ability to overcome the quinine block of RVD
      indicated that RVD is mediated by a quinine-sensitive cation transport mechanism
      that is independent of the swelling-induced anion transport mechanism. Barium (1
      4 mM), another K channel blocker, slowed the rate of RVD, while 4-aminopyridine,
      charybdotoxin, tetraethylammonium chloride, tetrabutylammonium chloride, and
      gadolinium had no effect on RVD. Furthermore, RVD was not mediated by calcium
      activated conductances, since it occurred normally in Ca-free medium, in medium
      containing cadmium, and in BAPTA-loaded cells. Gramicidin produced little or no
      volume change in isotonic medium, suggesting that basal C1 permeability of both
      THP-1 and HL-60 cells is low. However, swelling induced an anion efflux pathway
      that is permeable to both chloride and bromide, but is impermeable to
      methanesulfonate and glutamate. The anion channel blocker 3,5-diiodosalicylic
      acid (DISA) antagonized RVD in both cell types. In conclusion, RVD in THP-1 and
      HL-60 cells is mediated by independent anion and cation transport mechanisms that
      involve both a DISA-sensitive anion pathway and a quinine-inhibitable K efflux
      pathway, neither of which requires increases in intracellular calcium to be
      activated.

PMID- 7514616
TI  - Nociceptive role of substance-P in the knee joint of a patient with congenital
      insensitivity to pain.
AB  - This case report describes the immunocytochemical examination of tissue from a 9
      year-old black child diagnosed with congenital insensitivity to pain at age 5. A
      recent fall and resulting patella fracture required surgical treatment. Biopsies
      of the distal pole and surrounding soft tissue, as well as a sample of his
      patellofemoral joint fluid, were taken at the time of partial patellectomy and
      analyzed for substance-P (SP). Morphologic staining of the patella showed a
      grossly degenerated patellofemoral articular surface. Examination of tissue
      sections stained either immunocytochemically with diaminobenzidine DAB or by a
      rhodamine fluorescent labeling technique showed no evidence of SP-positive nerve
      fibers. Furthermore, only a trace amount of SP (7.29 pg/ml) was detected in a
      sample of the patient's knee joint synovial fluid. This patient's absence of pain
      sensation in conjunction with the absence of SP nerve fibers in stained patella
      sections and identification of only trace levels of SP in his synovial fluid,
      further implicates this neuropeptide in nociceptive innervation of diarthrodial
      joints.

PMID- 7514615
TI  - A technique for the sequential isolation of RNA and DNA from embryos developed
      for screening for viruses.
AB  - A technique has been developed to detect RNA or DNA viruses in single embryos.
      This technique is based on sequential RNA and DNA isolation from the embryo and
      analysis of this nucleic acid by polymerase chain reaction. A constitutively
      expressed embryo gene (alpha subunit ATPase) is also analysed as an internal
      standard. Extraction of RNA was more efficient than that of DNA, however,
      positive results were obtained for the internal standard gene for 84% (RNA) and
      30% (DNA) of embryos tested.

PMID- 7514617
TI  - CD44 expression in Merkel cell carcinoma may correlate with risk of metastasis.
AB  - We retrospectively studied 25 cases of cutaneous primary, locally recurrent or
      metastatic Merkel cell carcinoma to see if expression of the cell surface marker
      CD44 correlated with metastatic potential. In 3 of 6 cases in which metastasis
      was documented, CD44 was found on membranes of tumor cells. Three cutaneous
      lesions associated with local metastasis did not express CD44. Three primary
      tumors expressed CD44 but had not disseminated at the time of this report; follow
      up after excision of the primary lesion in these cases was less than 6 months.
      None of the primary or locally recurrent Merkel cell carcinomas followed longer
      than 6 months (14 of 19 cases) expressed CD44. We conclude that expression of
      CD44 in Merkel cell carcinoma may eventually be of some value in the assessment
      of prognosis of cutaneous Merkel cell carcinoma.

PMID- 7514618
TI  - E-selectin and vascular cell adhesion molecule-1 as critical adhesion molecules
      for infiltration of T lymphocytes and eosinophils in atopic dermatitis.
AB  - To study the temporal and spatial relationship between infiltrating T-cell
      subsets or eosinophils and cell adhesion molecules on endothelial cells in skin
      lesions of atopic dermatitis (AD), we undertook immunohistochemical analysis
      using monoclonal antibodies against surface markers of T cells, eosinophil
      granule proteins and cell adhesion molecules. Predominant mononuclear cells in
      acute and chronic skin lesions were CD3, CD4 and CD45RO positive helper
      inducer/memory T cells. Their number was significantly and strongly correlated
      with the intensity of E-selectin expression. Eosinophils and deposition of
      eosinophil-derived granule proteins such as eosinophil cationic protein (ECP),
      major basic protein (MBP) and eosinophil peroxidase (EPO) were found constantly
      in acute lesions and only occasionally in chronic lesions. The total number of
      immunoreactive eosinophils and deposits of MBP, EPO and ECP were significantly
      and strongly correlated with the staining intensity of VCAM-1. In chronic lesions
      significant reduction of VCAM-1 expression paralleled occasional infiltration of
      eosinophils. Our results demonstrate the possibility that E-selectin and VCAM-1
      are the critical adhesion molecules for trafficking of memory T cells and
      eosinophils, respectively, into skin lesion of AD. Persistent expression of the
      adhesion molecules may be related to prolongation of the skin lesion in AD.

PMID- 7514620
TI  - Confluent education: an integrative method for nursing (continuing) education.
AB  - Confluent education is presented as a method to bridge the gap between cognitive
      and affective learning. Attention is focused on three main characteristics of
      confluent education: (a) the integration of four overlapping domains in a
      learning process (readiness, the cognitive domain, the affective domain and
      responsibility); (b) the promotion of personal growth and interpersonal
      relationships by the development of awareness, and (c) the identification and dis
      identification of teacher and participants. How confluent education can take
      place in practice is illustrated by presenting the way in which this method is
      applied in a nursing continuing education programme entitled 'Pain assessment and
      management in surgical-oncological patients'.

PMID- 7514619
TI  - Eccrine angiomatous hamartoma (nevus): immunohistochemical findings and review of
      the literature.
AB  - Eccrine angiomatous hamartoma (nevus) is a rare form of congenital tumorous
      malformation with proliferation of eccrine secretory coils and ducts, surrounding
      capillary angiomatous channels and occasionally other minor elements. To date,
      there have been only about 24 cases reported in the literature. We report an
      additional case with more detailed description of the microscopic findings,
      including immunohistochemical observations. The patient was a 28-year-old female
      who presented with painless, flesh- to reddish brown-colored, violaceous or
      bluish subcutaneous nodules on the extremities and trunk. The tumors did not show
      sweating following exertion. The histologic features were comparable to the
      previously reported cases. The hamartomatous eccrine sweat glands and ducts and a
      few apocrine glands demonstrated qualitatively diminished antigens commonly found
      in the eccrine sweat apparatuses, such as carcinoembryonic antigen (CEA) and S
      100 protein. The findings of CD34, CD44, human nerve growth factor receptor and
      Ulex europaeus antigens have not been previously reported. The histologic
      features suggested a "hamartomatous" growth rather than a true neoplastic
      process.

PMID- 7514624
TI  - Does ursodeoxycholic acid have a place in the treatment of amiodarone-induced
      cholestasis?

PMID- 7514621
TI  - Distribution of NADPH-diaphorase-positive nerves supplying the human urinary
      bladder.
AB  - Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry
      was used as a marker for neuronal nitric oxide synthase in human bladder tissue.
      A plexus of NADPHd-containing nerve fibres was observed in bladder biopsies taken
      from both the lateral wall and trigone regions. Varicose terminals were present
      in smooth muscle bundles of the detrusor and trigone, and more commonly within
      the submucosal layer. Reactive fibres were seen running immediately beneath and
      along the urothelium, and additional nerves formed perivascular plexi around some
      blood vessels. Fewer positive nerve processes were observed in the trigone region
      in comparison to the bladder wall. NADPHd-reactive neuronal perikarya were
      present within intramural ganglia, some of which were in close proximity to
      NADPHd-stained varicosities. The results indicate that nitric oxide may be
      involved in the regulation of bladder function in humans.

PMID- 7514623
TI  - Alterations in neural pathways to the urinary bladder of the rat in response to
      streptozotocin-induced diabetes.
AB  - Voiding dysfunction in diabetics has been attributed to a variety of causes
      including an axonopathy in autonomic pathways to the urinary bladder. The present
      study was undertaken to determine whether changes occurred in afferent and
      efferent neurons supplying bladders of streptozotocin (STZ)-induced diabetic
      rats. Nine weeks after STZ treatment, the mean cross-sectional area for
      retrogradely labeled (Fluoro-Gold) bladder neurons in the major pelvic ganglion
      (MPG) was greater in diabetics (364 microns 2) than controls (300 microns 2). The
      number of labeled neurons was similar in these groups. In contrast, mean cross
      sectional areas of bladder afferent neurons labeled with WGA-HRP in the L6 and S1
      dorsal root ganglia (DRG) were smaller (393 microns 2) in diabetics than in
      normal rats (528 microns 2). In addition, very few DRG neurons were labeled in
      STZ-treated rats and transganglionic labeling of bladder afferent projections in
      the L6 and S1 spinal cord with WGA-HRP was sparse. Radioimmunoassay studies
      revealed that substance P was reduced by 70% in the MPG and by 40% in L6 DRG, yet
      this peptide was unchanged in the bladders of diabetic rats. The amounts of VIP
      in the MPG and DRG of diabetics and controls were similar, while VIP in the
      bladder was increased in diabetics. These observations indicate that both
      afferent and efferent neurons innervating the urinary bladder are altered in the
      STZ-induced diabetic rat. In addition, axonal transport in visceral afferent
      pathways may be disrupted.

PMID- 7514622
TI  - Properties of putative cardiac and non-cardiac neurones in the rat stellate
      ganglion.
AB  - Intracellular recordings were made from isolated left or right stellate ganglia
      of Wistar rats and the morphology of neurones studied after intracellular
      injection of hexammine cobaltic chloride or back-filling from the post-ganglionic
      nerve with cobalt lysine complex. The experiments attempted to identify the
      location, electrophysiological properties, morphology and chemosensitivity of
      putative cardiac neurones in the ganglion. These were identified by antidromic
      activation of the axon in a cardiac nerve and compared with neurones projecting
      towards the brachial plexus (non-cardiac neurones). Putative cardiac neurones
      were localized in the ganglion around the postganglionic nerve entry zone and
      showed considerable morphological diversity. They had complex dendritic trees
      with, on average, seven dendrites. They included both phasic and tonic neurones
      and were depolarized by muscarinic agonists, angiotensin and substance P; they
      invariably had a synaptic input from the sympathetic trunk and from a T1 or T2
      ramus and, in 16% of cells, from a cardiac nerve. Non-cardiac neurones were more
      widely scattered through the stellate ganglion but were not clearly different in
      morphology, resting membrane potential or the proportion of phasic and tonic
      cells from putative cardiac neurones. They also showed depolarizing responses to
      muscarinic agonists, angiotensin and substance P. Angiotensin responses of
      stellate ganglion cells were blocked by the peptide antagonist, saralasin (1
      microM).

PMID- 7514625
TI  - A multilabeling technique for simultaneous demonstration and quantitation of Ki
      67 and nucleolar organizer regions (AgNORs) in paraffin-embedded tissue.
AB  - Although many investigators have demonstrated a relationship between argyrophilic
      nucleolar organizer regions (AgNORs) and Ki-67 expression in solid tumors, no
      previous studies have simultaneously assessed the relationship between AgNOR and
      Ki-67 expression in paraffin-embedded tissue. We describe a method for
      simultaneous demonstration and quantitation of Ki-67 and AgNORs in routinely
      processed tissue. The Ki-67 equivalent monoclonal antibody MIB1, which can detect
      proliferative activity in routinely processed tissue with microwave heating, was
      employed. Fresh human tonsil tissue was fixed in formalin and embedded in
      paraffin for Ki-67/AgNOR dual staining. Image analysis was employed for
      quantitation of AgNOR staining in Ki-67-positive and Ki-67-negative nuclei. The
      double-staining procedure had no measurable effect on the individual parameters:
      Ki-67 labeling index, mean AgNOR number (NN), and NOR percentage nuclear area
      (NPNA). However, microwave processing for Ki-67 immunostaining significantly
      increased nuclear area (NA) and AgNOR area (AA). A significant difference was
      found between Ki-67-positive and Ki-67-negative cells for NN (p < 0.001), NA (p <
      0.001), AA (p < 0.001), and NPNA (p < 0.001). These results suggest a direct
      relationship between AgNOR and Ki-67 in paraffin-embedded tissue.

PMID- 7514626
TI  - A simple, rapid method for isolating RNA from paraffin-embedded tissues for
      reverse transcription-polymerase chain reaction (RT-PCR).
AB  - Described here is a simple, rapid technique for isolating RNA from archived
      formalin-fixed, paraffin-embedded tissues (PETs). Using this modified acid
      guanidinium thiocyanate method, RNA sufficient as a template for the reverse
      transcription-polymerase chain reaction (RT-PCR) can be isolated in 2 hr from a
      single 20-microns-thick section of tissue. Spliced mRNA corresponding to portions
      of the estrogen receptor (ER) gene was successfully amplified from fixed,
      embedded human breast cancers containing increased amounts of ER protein. This
      method makes it feasible to safely and efficiently isolate RNA from large numbers
      of routinely processed paraffin blocks for retrospective studies of endogenous
      proteins such as hormone receptors, oncogenes, and viruses.

PMID- 7514628
TI  - Role of CD44 in the development of natural killer cells from precursors in long
      term cultures of mouse bone marrow.
AB  - The role of the adhesion molecule CD44 in the development of NK cells was
      analyzed in a mouse long-term bone marrow culture system. After 4 wk of culture
      (day 0), recombinant human IL-2 was added and 13 days later the cells generated
      were shown to have substantial cytotoxic activity against YAC-1 and to be
      enriched for NK cells, as assessed for NK-1.1 phenotype by flow cytometric
      analysis. Physical separation between stroma and precursors partially inhibited
      proliferation and, consequently, a lower number of cytotoxic cells were produced.
      Similar results were obtained when an anti-CD44 mAb was added together with IL-2
      at day 0. The disruption of hyaluronic acid (HA), one of the ligands of CD44, by
      hyaluronidase or the competition for the binding of CD44 by soluble HA added with
      IL-2 on day 0 inhibited both proliferation and development of cytotoxicity to a
      greater degree than did anti-CD44. These results indicate that interaction of
      CD44 with HA plays an important role in the development of pre-NK cells into
      cytotoxic effector cells.

PMID- 7514627
TI  - Autoradiographic visualization of 35S-labeled cRNA probes combined with
      immunoperoxidase detection of choleragenoid: a double-labeling light microscopic
      method for in situ hybridization and retrograde tract tracing.
AB  - We describe a protocol for simultaneous light microscopic visualization of a
      neuron's efferent projections and its expression of mRNA. We have combined
      immunohistochemical visualization of the retrograde marker cholera toxin subunit
      B (CTb) with autoradiographic visualization of 35S-labeled cRNA probes.
      Injections of CTb were made into rat brain. Immunoreactivity for CTb was
      demonstrated by modification of the peroxidase-anti-peroxidase
      immunohistochemical technique, with DAB and nickel ammonium sulfate or cobalt
      acetate as chromogen. On the same sections, in situ hybridization was performed
      with a 35S-labeled RNA probe complementary to preproenkephalin mRNA or tyrosine
      hydroxylase mRNA. Many double-labeled neurons were detected. These neurons
      contained peroxidase reaction product and were covered by an accumulation of
      silver grains in the overlaying emulsion layer. The present method has several
      advantages over double-labeling methods using the combination of fluorescent
      tracers and oligonucleotide probes. Both reaction products are permanent and can
      be visualized simultaneously by light microscopy. Furthermore, both CTb and cRNA
      probes are very sensitive markers. In addition, the sections can be
      counterstained.

PMID- 7514629
TI  - A minority subpopulation of CD4+ T cells directs the development of naive CD4+ T
      cells into IL-4-secreting cells.
AB  - The culture of CD4+ T cells with immobilized anti-CD3 and IL-2 generated a
      population of cells that produced both IL-4 and IFN-gamma on restimulation. In
      contrast, CD4+ T cells stimulated with immobilized anti-V beta 6 under otherwise
      identical culture conditions generated cells that produced IFN-gamma but not IL-4
      on restimulation. This difference was likely a result of quantitative differences
      in the concentration of responding T cells in the two cultures rather than to
      qualitative differences between the two Abs. Anti-CD3 induced development of IL-4
      secreting cells required IL-4 during the primary stimulation. This endogenous IL
      4 in primary cultures was produced by cells with a Mel-14low, memory/activated
      phenotype but not by cells expressing the Mel-14high, naive phenotype. However,
      co-cultures of Mel-14high and Mel-14low populations marked with different Ly-5
      allotypes demonstrated that nearly all of the IL-4-secreting cells that developed
      from primary cultures were generated from the Mel-14high population. Moreover,
      Mel-14high T cells could generate IL-4-secreting cells only in the presence of
      Mel-14low T cells or rIL-4. In addition, co-culture of CD4+, Mel-14low T cells
      from IL-4-deficient mice with CD4+, Mel-14high T cells from wild-type mice did
      not lead to the development of IL-4-secreting cells. Thus, IL-4, made by a
      minority population of previously differentiated CD4+ T cells, can induce the
      development of IL-4-secreting cells from the naive T cells but naive CD4+ T cells
      themselves do not develop into IL-4-secreting cells.

PMID- 7514630
TI  - Inhibition of T cell activation by the extracellular matrix protein tenascin.
AB  - Tenascin (TN) is an extracellular matrix protein that is expressed widely in the
      fetus and sparingly in the adult, but reappears at high levels in certain areas
      of tissue insult such as tumor matrices and sites of wound healing. We show here
      that soluble TN inhibits proliferation of human T cells in response to alpha CD3
      Ab co-immobilized with the extracellular matrix protein fibronectin (FN). TN also
      inhibits proliferation driven by alpha CD3/IL-2 or by phorbol ester/IL-2, and it
      prevents high level induction of IL-2R. The presence of TN in culture medium does
      not detectably alter the pattern of tyrosine phosphorylation resulting from T
      cell triggering with alpha CD3, but at later time points prevents the appearance
      of functional NF-AT1 transcription factor complexes in T cell nuclear extracts.
      These findings are consistent with the postulated role for TN as a natural
      antagonist to FN action, and suggest that T cell responses occurring at tissue
      sites in which TN is expressed could be influenced by its presence.

PMID- 7514631
TI  - Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7
      2) expression on murine dendritic cells.
AB  - Dendritic cells (DC) play a critical role in the initiation of T cell-mediated
      immune responses, and express costimulatory molecules that are required for
      optimal activation of unprimed T cells. Studies on the regulation of the
      costimulatory molecules on DC have produced evidence from several systems that GM
      CSF can up-regulate expression of CTLA4 counter receptor (CTLA4-CR) (but not
      intercellular adhesion molecule 1 (ICAM-1) and heat stable Ag (HsAg)) on DC. This
      is demonstrated on splenic DC, Langerhans cells, kidney DC in culture, and in a
      skin-explant culture system, in which the increased expression of CTLA4-CR on
      Langerhans cells (LC) occurs concomitantly with their migration out of skin.
      Interestingly, despite the ability of both GM-CSF and IFN-gamma to increase CTLA4
      CR and maintain similar levels of ICAM-1, HsAg, and MHC molecule expression, the
      functional consequences of these cytokines on splenic DC are distinctly
      different. GM-CSF enhances the ability of DC to stimulate both T cell
      proliferation and cytokine release, whereas IFN-gamma causes no increase in
      immunostimulatory function. Further analysis of the CTLA4-CR on these cell
      populations by using the GL-1 and IG10 mAbs has shown that GM-CSF-cultured DC
      express high levels of both B7-1 and B7-2, whereas IFN-gamma-cultured DC express
      increased levels of only B7-2. These results suggest that optimal stimulation of
      unprimed T cells to proliferate and release cytokines may require participation
      of both of these CTLA4 counter receptors, and confirm the importance of GM-CSF
      for the maturation of DC into potent stimulators of T cell activation.

PMID- 7514632
TI  - Costimulator dependence of lymphokine secretion by naive and activated CD4+ T
      lymphocytes from TCR transgenic mice.
AB  - The role of costimulation in Ag-induced responses of naive and differentiated IL
      2 and IL-4-producing CD4+ T cells has been examined using cells from mice
      expressing a transgenic TCR specific for cytochrome c (81-104) + I-Ek. IL-2
      secretion by naive and pre-activated T cells is dependent on costimulation,
      because it is not induced with chemically fixed APCs and is significantly
      inhibited by the B7 antagonist, CTLA4-Ig. In contrast, IL-4 secretion by in vitro
      differentiated Th2-like cells is relatively independent of costimulators. Thus,
      the requirement for costimulation is related more to lymphokine secretion
      profiles than to the previous activation status of CD4+ T lymphocytes.

PMID- 7514633
TI  - Cytokine regulation of early human lymphopoiesis.
AB  - An in vitro culture system in which bone marrow-derived fibroblast-like cells
      support the growth of TdT+ colonies derived from CD34+/CD10- human bone marrow
      progenitor cells has recently been described. The regulatory role of cytokines
      during early B lineage commitment was investigated using this culture system.
      Expression of IL-7, a cytokine that induces proliferation of B cell precursors,
      was detectable in the adherent layer by PCR and bioassay. Lymphoid progenitor
      colonies were inhibited by neutralizing anti-IL-7 Ab, suggesting that IL-7
      produced by the adherent layer was required even in the earliest recognizable
      stages of human B cell lymphopoiesis. IL-1 alpha, IL-4, and TNF-alpha inhibited
      lymphoid progenitor colonies in a dose-dependent fashion. Neutralizing Ab to IL-1
      alpha, IL-4, or TNF-alpha did not increase lymphoid progenitor colonies,
      suggesting that inhibitory concentrations of these cytokines are not
      constitutively elaborated in the adherent layer. Recombinant Steel factor and IL
      6 as well as neutralizing Abs to these cytokines did not significantly affect
      lymphoid progenitor colonies, arguing against an important role for these
      cytokines in early human B lymphopoiesis. These results indicate that IL-7
      provided by the bone marrow microenvironment is a critical growth factor at the
      earliest recognizable stages of human lymphopoiesis. IL-1 alpha, IL-4, and TNF
      alpha have been shown to indirectly stimulate release of myeloid growth factors.
      The inhibition of lymphopoiesis by these cytokines suggests a possible mechanism
      for the observed reciprocal relationship between lymphoid and myeloid supportive
      bone marrow microenvironments.

PMID- 7514634
TI  - Prostaglandin E2 inhibits T cell-dependent Ig secretion by neonatal but not adult
      lymphocytes.
AB  - Prostaglandin E2 (PGE2) inhibits Ig production by adult B cells stimulated with
      Staphylococcus aureus and IL-2, and inhibits the production of IL-2 by anti-CD3
      stimulated T cells. By contrast, PGE2 did not inhibit T cell-dependent Ig
      production by adult B cells. However, T cell-dependent Ig secretion by neonatal B
      cells was markedly inhibited by PGE2 even in the presence of supplemental IL-2.
      Forskolin, a direct activator of adenylate cyclase, and dibutyryl cAMP caused
      similar effects. PGE2 inhibited T cell-dependent Ig secretion by both neonatal
      CD5+ and CD5- B cells but did not inhibit Ig secretion by either CD5+ or CD5-
      adult peripheral blood B cells. PGE2 did not inhibit IL-2-dependent anti-CD3
      stimulated neonatal T cell proliferation or T cell-dependent neonatal B cell
      proliferation. PGE2 inhibited neonatal B cell Ig production when addition was
      delayed, suggesting that initial B cell activation and proliferation were not
      blocked, but that PGE2 prevented subsequent differentiation. In addition, PGE2
      inhibited neonatal T cell help independent of cytokine production. PGE2-induced
      cAMP levels in neonatal B and T cells were not different from adult levels. These
      results indicate that production of Ig by neonatal lymphocytes is uniquely
      sensitive to the inhibitory effects of agents such as PGE2 that elevate cAMP
      levels. This sensitivity may contribute to the suppressed in vivo responses of
      human neonatal B cells.

PMID- 7514635
TI  - Ligation of MHC class I and class II molecules can lead to heterologous
      desensitization of signal transduction pathways that regulate homotypic adhesion
      in human lymphocytes.
AB  - Engagement of lymphocyte MHC class I and class II Ags activates an array of
      intracellular signal transduction pathways that up-regulates the activity of cell
      surface adhesion receptors, resulting in homotypic cell-cell aggregation. In this
      study, engagement of MHC class I and class II molecules with specific mAbs was
      shown to also inhibit lymphocyte homotypic adhesion. Two mAbs reactive with class
      II Ag, homotypic adhesion blocking mAb (HAB)-2, and HAB-3, and one mAb reactive
      with class I Ag, HAB-4, were generated that inhibited homotypic adhesion of
      activated lymphocytes and B and T cell lines at concentrations as low as 0.1
      microgram/ml. Binding of these mAbs resulted in heterologous desensitization of
      other surface signal transduction molecules as homotypic adhesion induced through
      class I, class II, CD19, CD20, CD39, CD40, Leu-13, and PMA was also inhibited.
      The spontaneous adhesion exhibited by some cell lines was also abrogated by
      binding of these mAbs. Abs that either induced, blocked, or had no effect on
      adhesion bound to distinct epitopes on class I, whereas the anti-class II mAbs
      recognized either distinct or overlapping epitopes. Thus, engagement of distinct
      epitopes on MHC molecules can result in homologous or heterologous
      desensitization of cell-surface signaling molecules. The induction or inhibition
      of homotypic adhesion through class I molecules did not require the presence of
      the cytoplasmic domain, as deletion of this portion of the class I molecule had
      no effect. In contrast, the transmembrane region was essential for signal
      transduction as the mAbs binding to a chimeric molecule in which the
      transmembrane and cytoplasmic domains of class I were exchanged with those of the
      HB15 molecule did not induce or inhibit homotypic adhesion. Although this report
      is the first demonstration that homotypic adhesion can be influenced in a
      negative manner through MHC molecules, these findings demonstrate a considerable
      level of cross-talk between MHC molecules and other cell-surface receptor systems
      and their signal transduction pathways, and suggests that MHC class I and class
      II molecules may serve important roles in the regulation of adhesive events
      during lymphocyte activation.

PMID- 7514636
TI  - Functionally important amino acids in the TCR revealed by immunoselection of
      membrane TCR-negative T cells.
AB  - A spontaneous TCR cell surface variant (3P11) of the Jurkat T cell line is
      described and characterized. 3P11 was selected by incubation of Jurkat cells with
      anti-TCR mAb followed by passage through Ig anti-Ig columns and cloning. 3P11
      contained mRNA for both Ti alpha and Ti beta and CD3 gamma, delta, epsilon and
      zeta. Biochemical analyses demonstrated that all of the TCR components were
      produced in 3P11 cells. The Ti alpha beta/CD3 gamma delta epsilon zeta complex
      was assembled in the endoplasmic reticulum but the zeta did not associate with
      this complex. Epitopes recognized by the Ti beta chain specific mAb beta F1 and
      JOVI as well as anti-V beta 8 were affected in the 3P11 Ti beta chain indicating
      that the 3P11 Ti beta chain was mutated. Transfection of a wild-type Ti beta cDNA
      into 3P11 cells reconstituted TCR expression. Sequence analyses of the 3P11 Ti
      beta chain demonstrated a guanine to adenine change in the second nucleotide of
      the triplet coding for cysteine191 resulting in a cysteine to tyrosine exchange.
      Cysteine191 is the C-terminal cysteine involved in the intrachain disulfide bond
      in the C domain of the Ti beta chain; thus, the 3P11 Ti beta chain did not
      contain this disulfide bond. Transfection of a site-directed Ti beta chain
      containing the 3P11 mutation into a Ti beta negative variant of the Jurkat cell
      line resulted in a TCR phenotype identical with 3P11 demonstrating that the
      mutation identified in the 3P11 Ti beta chain was the sole cause for the 3P11
      defect.

PMID- 7514637
TI  - Zymosan-induced IL-8 release from human neutrophils involves activation via the
      CD11b/CD18 receptor and endogenous platelet-activating factor as an autocrine
      modulator.
AB  - We have investigated mechanisms that regulate the generation of IL-8 by human
      neutrophils on contact with zymosan particles in vitro. Zymosan stimulated IL-8
      production, which increased with increasing particle numbers and was abolished by
      the protein synthesis inhibitor cycloheximide. IL-8 was detectable in culture
      supernatant at 8 h reaching a maximum at 24 h. In all further experiments IL-8
      was measured at 24 h. mAbs to neutrophil CD18 (60.3 and 6.5E) caused a marked
      suppression of IL-8 generation, but only if added up to 2 h after zymosan
      stimulation. An anti-CD11b mAb (KIM 225) substantially inhibited zymosan-induced
      IL-8 release. We investigated whether other mediators generated during
      phagocytosis modulate IL-8 production. Two selective platelet-activating factor
      (PAF) receptor antagonists, WEB 2086 and UK 74505, produced a profound
      suppression of IL-8 generation, when added within 30 min to 1 h of zymosan
      stimulation. An IL-1R antagonist, a leukotriene B4 antagonist, and an anti-TNF
      alpha Ab had no effect on IL-8 generation. FMLP, PAF, and a stable PAF agonist
      did not stimulate significant IL-8 production, however, a calcium ionophore
      (A23187) did induce IL-8 release and this was suppressed by UK 74505. We conclude
      that zymosan-induced IL-8 generation involves stimulation of the neutrophil via a
      CD11b/CD18 receptor resulting in beta 2-integrin mediated activation of signal
      transduction mechanisms that leads to cytokine synthesis. Furthermore,
      endogenously generated PAF, or a PAF, or a PAF-like molecule, appears to have an
      autocrine function in regulating this pathway of IL-8 production at an early
      stage after the interaction between the neutrophil and the particles.

PMID- 7514638
TI  - CD11b/CD18 (Mac-1) is required for degranulation of human eosinophils induced by
      human recombinant granulocyte-macrophage colony-stimulating factor and platelet
      activating factor.
AB  - Recent evidence suggests adhesion molecules play an important role in the
      function of leukocytes. Because human eosinophils are known to express beta 2
      integrins, we hypothesized that these adhesion molecules mediate the effector
      function of eosinophils. Normal human eosinophils incubated in albumin-coated
      polystyrene plates released granule protein and produced superoxide anion when
      stimulated with human recombinant granulocyte-macrophage CSF (rGM-CSF), platelet
      activating factor (PAF), or PMA. Simultaneous monitoring of eosinophil adhesion
      and degranulation showed that degranulation was always preceded by cellular
      adhesion regardless of stimuli. Furthermore, eosinophil degranulation induced by
      human rGM-CSF and PAF was abolished in suspension culture of the cells when the
      cell suspensions were gently stirred. To identify the molecules involved in this
      adhesion-dependent degranulation, we have investigated the effects of mAbs (mAb)
      against beta 2 integrins. mAb reactive with CD18 markedly inhibited the
      eosinophil adhesion and degranulation induced by PAF and human rGM-CSF. mAb
      reactive with CD11b also moderately inhibited the adhesion and degranulation. In
      contrast, mAb reactive with CD11a slightly enhanced or showed no effect on the
      adhesion and degranulation by human rGM-CSF or PAF. Superoxide production induced
      by human rGM-CSF and PAF was also abolished by the treatment of cells with anti
      CD18 mAb. mAb against CD11b and CD18 had little effect on degranulation and
      superoxide production induced by PMA. These results indicate that CD11b/CD18 (Mac
      1)-dependent cellular adhesion plays an important role in the degranulation and
      superoxide production of eosinophils induced by human rGM-CSF and PAF, and that
      these mechanisms may be employed in vivo where eosinophils contact with stromal
      cells and/or proteins.

PMID- 7514639
TI  - IL-6 production by rat peritoneal mast cells is not necessarily preceded by
      histamine release and can be induced by bacterial lipopolysaccharide.
AB  - Mast cells produce a number of cytokines including IL-6. In view of the large
      amounts of de novo synthesis induced by the activation of rat peritoneal mast
      cells and previous observations of expression of this cytokine by human lung mast
      cells, we have studied the regulation of IL-6 production. We examined the
      hypothesis that mast cell IL-6 production is not related to previous histamine
      release. Highly purified rat peritoneal mast cells were activated with anti-IgE,
      calcium ionophore A23187, or LPS. Histamine was used as a marker of preformed
      mediator release and IL-6 production was assessed by using the B9 hybridoma
      growth factor bioassay. Anti-IgE activation of rat peritoneal mast cells induced
      IL-6 production and histamine release. In contrast, LPS activation induced
      substantial, serum-dependent, IL-6 production without a significant level of
      histamine release. No preformed IL-6 was detected in the cells. Calcium ionophore
      induced histamine release from mast cells to a greater extent than did anti-IgE,
      but no A23187-induced IL-6 production was observed. A23187-treated cells retained
      high viability and produced a significant amount of TNF-alpha. To further examine
      the concordance of IL-6 production and histamine release we used mast cell
      stabilizing drugs. Dexamethasone and nedocromil significantly inhibited IL-6
      production in response to anti-IgE. Our results demonstrate that there is not a
      direct relationship between mast cell degranulation and IL-6 production. Our
      observations are important for understanding the role of mast cells in
      inflammation and for developing strategies to modulate mast cell function in
      disease.

PMID- 7514641
TI  - Clonal expansion and persistence of human T cells specific for an immunodominant
      myelin basic protein peptide.
AB  - TCR rearrangements were used to probe the clonal origin of myelin basic protein
      (MBP)-reactive T cells from patients with multiple sclerosis (n = 7) and normal
      subjects (n = 3). The majority of MBP-specific T cell lines were specific for the
      immunodominant MBP(84-102) and MBP(143-168) peptides and were restricted by HLA
      DR molecules. In two patients with the DR2 haplotype, the T cell response to MBP
      was focused on the MBP(84-102) peptide. In both patients, in vivo expanded
      population(s) (three expanded populations in the first patient, one expanded
      population in the second patient) dominated the response to the MBP(84-102)
      peptide. Two MBP(84-102)-specific T cell clones from a normal subject with the
      DR2 haplotype were also found to have identical TCR sequences. Clonality was
      proven by demonstrating that independent clones had identical TCR alpha- and TCR
      beta-chain sequences as well as identical sequences of a TCR gamma-chain or of a
      second TCR alpha-chain rearrangement. Repeated analysis of one patient after 13
      mo demonstrated that the three expanded clones had persisted in vivo. A
      representative of one of the expanded clones was again obtained after 31 mo by IL
      2 stimulation suggesting that this clone was activated in vivo. These data
      suggest that the response to human MBP is dominated in at least some subjects by
      expanded clones that may persist in vivo for relatively long periods of time.

PMID- 7514640
TI  - Pattern of anti-small nuclear ribonucleoprotein antibodies in MRL/Mp-lpr/lpr mice
      suggests that the intact U1 snRNP particle is their autoimmunogenic target.
AB  - MRL/Mp-lpr/lpr (MRL/lpr) mice develop anti-Sm Abs that bind the B and D proteins
      of the U1 and other U small nuclear ribonucleoproteins (snRNPs). Humans with SLE
      also develop anti-Sm, but in contrast to MRL/lpr mice, anti-Sm Abs in humans are
      virtually always accompanied by anti-snRNP Abs that bind the A and 70 kDa
      proteins of the U1 snRNP. In this study, we identified anti-U1 snRNP Abs in 60%
      of MRL/lpr mice (40 of 66 animals), with the earliest and most frequent response
      directed against the A protein. This response was either accompanied or closely
      followed by Abs to other snRNP proteins, including the 70-kDa protein of the U1
      particle and the B and D proteins that represent the anti-Sm response. Other U
      snRNPs were rarely bound by these sera, analogous to previous observations in
      human SLE. Using in vitro translated 5' and 3' deletion mutants, we found that
      these early Abs principally bound an epitope on the COOH-terminal of the murine A
      protein. As shown previously, human sera with anti-U1 snRNP reactivity bind a
      similar epitope. In summary, we have shown that anti-snRNP Abs in MRL/lpr mice
      are composed of a linked group of specificities against proteins of the U1 snRNP
      particle, similar to human SLE. These observations, in conjunction with our
      previous findings that intact snRNPs are necessary for diversification of Abs in
      normal mice immunized with snRNPs, strongly suggests that intact U1 particles may
      be targets of the immune response in this disease.

PMID- 7514642
TI  - Denatured muscle grafts for nerve repair in an experimental model of nerve damage
      in leprosy. 2. Recovery of peripheral peptide-containing nerves assessed by
      quantitative immunohistochemical study.
AB  - A marked depletion of neuropeptide-immunoreactive nerves, a consequence of the
      nerve damage which is commonly found in leprosy, has been reported in peripheral
      tissues of leprosy patients and of a leprosy animal model. The aim of this study
      was to investigate peripheral reinnervation following a denatured autologous
      muscle graft in an animal model of leprosy nerve damage. Possible reinnervation
      of the foot-pad skin was studied by immunohistochemistry using antisera to the
      neuronal marker protein gene product 9.5 (PGP), the neuropeptides calcitonin gene
      related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP),
      and the C-flanking peptide of neuropeptide Y (CPON). The extent of the
      reinnervation process was assessed by image analysis quantification at different
      time points. At 8 weeks after muscle grafting, there were small numbers of
      immunoreactive nerves (p < 0.05). At 12, 16, and 20 weeks postoperatively there
      was a gradual increase in all immunostaining. At 20 weeks, no significant
      difference was found for PGP-, CGRP-, and SP-immunoreactive nerves in the
      epidermal and subepidermal layers compared to control (contralateral) tissue. In
      experimental tissue the recovery of immunoreactive nerves around sweat glands
      took longer (up to 12 weeks) than in other skin compartments, but after that time
      the recovery was rapid and at 20 weeks no difference was measured for VIP
      immunoreactive nerves in comparison with controls. Around blood vessels, the
      recovery of CGRP- and CPON-immunoreactive fibers was slow, and at 20 weeks a
      difference with control samples (p < 0.01) was noted. In the same area, there was
      no significant difference for PGP immunoreactivity between controls and tissues
      at 20 weeks. In contrast, the immunoreactive nerve bundles in the dermis showed a
      faster recovery than nerves in other skin areas, with amounts similar to controls
      at 20 weeks. The significant recovery of immunoreactive nerves, in particular of
      those containing sensory neuropeptide, is consistent with the described
      functional recovery.

PMID- 7514643
TI  - Nonlinear predictive interpolation. A new method for the correction of ectopic
      beats for heart rate variability analysis.
AB  - Heart rate variability (HRV) analysis is a technique that uses the beat-to-beat
      variations in RR intervals as a measure of the level of activity of the autonomic
      nervous system. However, the presence of ectopic beats can alter measures of HRV
      by introducing mathematical artifact and thus, prevent accurate determinations of
      HRV. Simple exclusion of those portions of data that contain ectopy from analysis
      inappropriate because (1) it can lead to a substantial reduction in the amount of
      data available for analysis and (2) if the presence (and frequency) of ectopic
      beats is correlated with specific alterations in autonomic tone, then the
      utilization of only ectopy-free data for analysis will lead to bias in the
      measures. For this reason, methods for the correction of ectopic beats have been
      devised and applied in the determination of HRV. The authors therefore propose a
      new method for the correction of ectopic beats: nonlinear predictive
      interpolation. Using the fact that beat-to-beat changes in heart rate occur in a
      deterministic fashion as the only assumption, the authors apply the methods of
      chaos theory in order to locate ectopy-free portions of the RR interval sequence
      that describe trajectories in phase space that are locally similar to that of the
      ectopy-containing segments. The authors then determine which of these
      trajectories most closely approximates that of a particular ectopy-containing
      segment, and use it to determine replacement RR intervals for the ectopic beats.

PMID- 7514646
TI  - 12-O-tetradecanoylphorbol 13-acetate and fibroblast growth factor increase the 30
      kDa substrate binding subunit of type II deiodinase in astrocytes.
AB  - Type II 5'-deiodinase (D-II) catalyzes the intracellular conversion of thyroxine
      (T4) to 3,5,3'-triiodothyronine (T3) in the brain. The D-II activity in
      astroglial cell cultures is induced by several pathways including cyclic AMP
      (cAMP), 12-O-tetradecanoylphorbol 13-acetate (TPA), and fibroblast growth factors
      (FGFs). We have examined the effect of TPA and FGFs on the 30-kDa substrate
      binding subunit of D-II, by affinity labeling with N-bromoacetyl-[125I]T4 in
      astroglial cells. TPA (0.1 microM), 20 ng/ml acidic FGF (aFGF), and 1 mM 8-bromo
      cyclic AMP all caused an increase in the 30-kDa protein. cAMP induced the
      greatest increase (fivefold) followed by TPA (3.2-fold) and FGF (2.8-fold).
      Glucocorticoids acted synergistically with cAMP and aFGF and promoted the effect
      of TPA. Affinity labeling was competitively inhibited by bromoacetyl-T4 >
      bromoacetyl-T3 > T4 > reverse T3 > iopanoic acid > T3 > 3,5,3'-triiodothyroacetic
      acid. The effect of TPA (0.1 microM) was maximum at 8 h and then gradually
      decreased. aFGF (20 ng/ml) plus heparin (17 micrograms/ml) induced a maximal 30
      kDa increase at 8 h, which stayed stable for up to 24 h. The effect of aFGF was
      concentration dependent. Of the other growth factors studied, only basic FGF and
      platelet-derived growth factor induced small increases in the 30-kDa protein.
      Epidermal growth factor had little effect. In vitro labeling of cAMP, TPA, and
      aFGF-stimulated cell sonicates resulted in an increase in the 30-kDa protein that
      paralleled the increase in D-II activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514644
TI  - Hyperpolarization-activated chloride currents in Xenopus oocytes.
AB  - During hyperpolarizing pulses, defolliculated Xenopus oocytes have time- and
      voltage-dependent inward chloride currents. The currents vary greatly in
      amplitude from batch to batch; activate slowly and, in general, do not decay;
      have a selectivity sequence of I- > NO3- > Br- > Cl- > propionate > acetate; are
      insensitive to Ca2+ and pH; are blocked by Ba2+ and some chloride channel
      blockers; and have a gating valence of approximately 1.3 charges. In contrast to
      hyperpolarization-activated chloride currents induced after expression of
      phospholemman (Palmer, C. J., B. T. Scott, and L. R. Jones. 1991. Journal of
      Biological Chemistry. 266:11126; Moorman, J. R., C. J. Palmer, J. E. John, J. E.
      Durieux, and L. R. Jones. 1992. 267:14551), these endogenous currents are
      smaller; have a different pharmacologic profile; have a lower threshold for
      activation and lower voltage-sensitivity of activation; have different activation
      kinetics; and are insensitive to pH. Nonetheless, the endogenous and expressed
      current share striking similarities. Recordings of macroscopic oocyte currents
      may be inadequate to determine whether phospholemman is itself an ion channel and
      not a channel-modulating molecule.

PMID- 7514647
TI  - Neurite outgrowth stimulated by the tyrosine kinase inhibitor herbimycin A
      requires activation of tyrosine kinases and protein kinase C.
AB  - Activation of tyrosine kinases is established as an important mechanism for
      controlling growth cone motility and neurite outgrowth. We have tested the
      effects of a range of tyrosine kinase inhibitors on neurite outgrowth from
      postnatal day 4 cerebellar granule cells cultured over confluent monolayers of
      3T3 fibroblasts. The only agent that had any effect was herbimycin A, which
      stimulated neurite outgrowth. The response is shown to be attributable to a
      direct effect of this tyrosine kinase inhibitor on neurones. The neurite
      outgrowth response to herbimycin A was inhibited by two other tyrosine kinase
      inhibitors, which on their own did not affect neurite outgrowth. The data suggest
      that the response to herbimycin A reflects either a direct or indirect activation
      of one or more protein tyrosine kinases. Independent signalling events down
      stream from tyrosine kinase activation underlying the neurite outgrowth response
      to herbimycin A include increased activity of protein kinase C and calcium influx
      into neurones through both N- and L-type calcium channels.

PMID- 7514645
TI  - Ionic permeability characteristics of the N-methyl-D-aspartate receptor channel.
AB  - N-methyl-D-aspartate (NMDA) receptor channels in cultured CA1 hippocampal neurons
      were studied using patch-clamp techniques. The purpose of the research was to
      determine the occupancy of the channel by permeant cations and to determine the
      influence of charged residues in or near the pore. The concentration dependence
      of permeability ratios, the mole-fraction dependence of permeability ratios, the
      concentration dependence of the single-channel conductance, and a single-channel
      analysis of Mg2+ block all independently indicated that the NMDA receptor behaves
      as a singly-occupied channel. More precisely, there is one permeant cation at a
      time occupying the site or sites that are in the narrow region of the pore
      directly in the permeation pathway. Permeability-ratio measurements in mixtures
      of monovalent and divalent cations indicated that local charges in or near the
      pore do not produce a large local surface potential in physiologic solutions. In
      low ionic strength solutions, a local negative surface potential does influence
      the ionic environment near the pore, but in normal physiologic solutions the
      surface potential appears too small to significantly influence ion permeation.
      The results indicate that the mechanism for the high Ca2+ conductance of the NMDA
      receptor channel is not the same as for the voltage-dependent Ca2+ channel
      (VDCC). The VDCC has two high affinity, interacting binding sites that provide
      high Ca2+ selectivity and conductance. The binding site of the NMDA receptor is
      of lower affinity. Therefore, the selectivity for Ca2+ is not as high, but the
      lower affinity of binding provides a faster off rate so that interacting sites
      are not required for high conductance.

PMID- 7514648
TI  - Forskolin and 3-isobutyl-1-methylxanthine increase basal and sodium nitroprusside
      elevated cyclic GMP levels in adult guinea-pig cerebellar slices.
AB  - In this study, the interaction between 3',5'-cyclic adenosine monophosphate
      (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) in [3H]adenine- or [3H]
      guanine-prelabelled adult guinea-pig cerebellar slices was investigated. Basal
      levels of [3H]cGMP were enhanced by forskolin, although no plateau was reached
      over the concentration range tested (0.1-100 microM). However, forskolin elicited
      a concentration-dependent, saturable potentiation of sodium nitroprusside (SNP)
      stimulated [3H]cGMP accumulation (forskolin EC50 value of 0.98 +/- 0.23 microM;
      10 microM forskolin produced a 1.8 +/- 0.3-fold potentiation of the SNP response
      at 2.5 min). The forskolin potentiation was observed at all concentrations of SNP
      tested (0.001-10 mM). Forskolin also elicited a large stimulation of [3H]-cAMP in
      [3H]adenine-prelabelled guinea-pig cerebellar slices; however, 1,9
      dideoxyforskolin failed to elicit either a [3H]cAMP response or a potentiation of
      the SNP-induced [3H]cGMP response at concentrations up to 100 microM.
      Pretreatment with oxyhaemoglobin (50 microM) inhibited the response to SNP (1 mM)
      and forskolin (10 microM), as well as the response evoked by the combination of
      SNP and forskolin. NG-Nitro-L-arginine (100 microM) inhibited the response to
      forskolin alone, but did not change the response to SNP or the potentiation
      induced by forskolin on SNP-induced [3H]cGMP levels. The protein kinase
      inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7; 100 microM),
      staurosporine (10 microM), polymyxin B (100 microM), and Ro 31-8220 (10 microM)
      had no effect on the [3H]cGMP response to either SNP or the combination of SNP
      plus forskolin. N6,2'-Dibutyryl cAMP, at concentrations up to 10 mM, was also
      without effect on [3H]cGMP levels induced by SNP.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7514649
TI  - Functional studies with substance P analogues: effects of N-terminal, C-terminal,
      and C-terminus-extended analogues of substance P on nicotine-induced secretion
      and desensitization in cultured bovine adrenal chromaffin cells.
AB  - Substance P (SP) and SP analogues, including C-terminal, N-terminal, and C
      terminus-extended analogues, have been investigated for their ability to modulate
      nicotine-induced secretion from bovine adrenal chromaffin cells in culture.
      Secretion was monitored by measuring the release of endogenous catecholamines by
      electrochemical detection following separation on HPLC and the release of
      endogenous ATP with an on-line luciferin-luciferase bioluminescence technique. SP
      is known to have the following two effects on nicotine-induced secretion of
      catecholamines (see Livett and Zhou, 1991): inhibition of the nicotinic response
      and protection against nicotinic desensitization. Secretion induced by 10(-5) M
      nicotine was inhibited 70-80% by SP, SP-methyl ester, and the C-terminus-extended
      analogue SP-Tyr12-NH2, 65% by (Ala3)SP-NH2, 45% by the C-terminal analogue SP(4
      11), and 20 and 5% by the N-terminal analogues SP(1-7) and SP(1-5), respectively,
      when these peptides were present at 3 x 10(-5) M concentrations. The order of
      potency was SP = SP-methyl ester = SP-Tyr12-NH2 > (Ala3)SP-NH2 > SP(4-11) > SP(1
      7) > SP(1-5). SP, SP-methyl ester, and (Ala3)SP-NH2 protected against nicotinic
      desensitization by 40-55%, and SP(4-11) protected by 20% (all at 3 x 10(-5) M).
      In contrast, the N-terminal analogues SP(1-7) and SP(1-5) and the C-terminus
      extended analogue SP-Tyr12-NH2 at 3 x 10(-5) M did not protect against nicotinic
      desensitization. Cyclo-SP(3-9), Ac-SP(3-9)-NH2, SP(3-9), and SP(3-6) had neither
      inhibitory nor facilitatory effects on secretion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7514650
TI  - Cross talk among cyclic AMP, cyclic GMP, and Ca(2+)-dependent intracellular
      signalling mechanisms in brain capillary endothelial cells.
AB  - C-type natriuretic peptide and sodium nitroprusside, a nitric oxide donor
      molecule, induced large increases in cyclic GMP formation in cultured rat brain
      capillary endothelial cells. Isoproterenol, a potent agonist of adenylate
      cyclase, potentiated the actions of C-type natriuretic peptide and of sodium
      nitroprusside. These actions were not observed in the presence of
      isobutylmethylxanthine and were mimicked by forskolin. Endothelin-1 had no action
      on basal cyclic GMP levels. It reduced cyclic GMP formation induced by C-type
      natriuretic peptide and sodium nitroprusside by about 50%. These actions involved
      an ETA receptor subtype and a Ca(2+)-dependent and protein kinase C-independent
      mechanism. Finally, increasing cyclic GMP slightly prolonged intracellular Ca2+
      transients induced by endothelin-1. The results suggest the presence of extensive
      cross talk among cyclic AMP, cyclic GMP, and Ca(2+)-dependent mechanisms in
      endothelial cells of brain microvessels. The relevance of the results to the
      regulation of the blood-brain barrier permeability is discussed.

PMID- 7514655
TI  - The problems with "wait and see" endodontics.

PMID- 7514654
TI  - Endodontic treatment finalization--a systematic endodontic-restorative approach.
AB  - Endodontic Treatment Finalization, a system integrating the fields of
      endodontics, periodontics and restorative dentistry, consists of ordered and
      logically sequenced steps to determine and provide the extent of treatment
      needed. The system is presented, along with both scientific and opinion-based
      rationale for its use.

PMID- 7514651
TI  - Role of Ca2+ in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-mediated
      polyphosphoinositide turnover in primary neuronal cultures.
AB  - Excitatory amino acid (EAA) receptors and EAA-mediated stimulation of
      polyphosphoinositide (poly-PI) turnover were studied in cultured neurons at
      different days in vitro (DIV). Six main observations have emerged from these
      studies: (a) Neurons increased their sensitivity to EAAs as a function of time in
      culture, indicated by increasing EAA-mediated poly-PI turnover. (b) Extracellular
      Ca2+ concentration played an important role in alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)-stimulated poly-PI turnover in cells at 4 DIV,
      whereas poly-PI turnover mediated by L-glutamate and trans-1-amino-cyclopentane
      1,3-dicarboxylic acid was not Ca(2+)-dependent. (c) A marked stimulation of poly
      PI turnover by AMPA was seen in the cultured neurons at 4 DIV, but not at 17 DIV,
      suggesting that a distinct EAA receptor sensitive to AMPA is transiently
      expressed. (d) The Ca2+ ionophore A23187 increased poly-PI turnover in cultured
      neurons, suggesting that Ca2+ entry is involved in stimulating poly-PI turnover.
      (e) Stimulation of poly-PI turnover by carbachol was greater in neurons at 17 DIV
      as compared with 4 DIV, and appeared to be Ca(2+)-dependent across DIV. (f) 6
      Cyano-7-nitroquinoxaline-2,3-dione, an antagonist for non-N-methyl-D-aspartate
      ionotropic EAA receptors, inhibited 100% and 35% of AMPA- and quisqualate-induced
      poly-PI turnover, respectively, suggesting an involvement of ionotropic
      AMPA/quisqualate receptors in stimulating poly-PI turnover.

PMID- 7514653
TI  - Photoneural regulation of rat pineal nitric oxide synthase.
AB  - We report here a photoneural regulation of nitric oxide synthase (NOS) activity
      in the rat pineal gland. In the absence of the adrenergic stimulation following
      constant light exposure (LL) or denervation, pineal NOS activity is markedly
      reduced. A maximal drop is measured after 8 days in LL. When rats are housed back
      in normal light:dark (LD) conditions (12:12), pineal NOS activity returns to
      normal after 4 days. A partial decrease in pineal NOS activity is also observed
      when rats are placed for 8 days in LD 18:6 or shorter dark phases, indicating
      that pineal NOS activity reflects the length of the dark phase. Because it is
      known that norepinephrine (NE) is released at night from the nerve endings in the
      pineal gland and this release is blocked by exposure to light, our data suggest
      that NOS is controlled by adrenergic mechanisms. Our observation may also explain
      the lack of cyclic GMP response to NE observed in animals housed in constant
      light.

PMID- 7514652
TI  - Blood to brain and brain to blood passage of native horseradish peroxidase, wheat
      germ agglutinin, and albumin: pharmacokinetic and morphological assessments.
AB  - Native horseradish peroxidase (HRP) and the lectin wheat germ agglutinin (WGA)
      conjugated to HRP are protein probes represented in the blood-brain barrier (BBB)
      literature for elucidating morphological routes of passage between blood and
      brain. We report the application of established pharmacokinetic methods, e.g.,
      multiple-time regression analysis and capillary depletion technique, to measure
      and compare bidirectional rates of passage between blood and brain for
      radioactive iodine-labeled HRP (I-HRP), WGA-HRP (I-WGA-HRP), and the serum
      protein albumin (I-ALB) following administration of the probes intravenously
      (i.v.) or by intracerebroventricular (i.c.v.) injection in mice. The
      pharmacokinetic data are supplemented with light and electron microscopic
      analyses of HRP and WGA-HRP delivered i.v. or by i.c.v. injection. The rates of
      bidirectional movement between blood and brain are the same for coinjected I-HRP
      and I-ALB. Blood-borne HRP, unlike WGA-HRP, has unimpeded access to the CNS
      extracellularly through sites deficient in a BBB, such as the circumventricular
      organs and subarachnoid space/pial surface. Nevertheless, blood-borne I-WGA-HRP
      enters the brain approximately 10 times more rapidly than I-HRP and I-ALB.
      Separation of blood vessels from the neocortical parenchyma confirms the entry of
      blood-borne I-WGA-HRP to the brain and sequestration of I-WGA-HRP by cerebral
      endothelial cells. Nearly half the I-WGA-HRP radioactivity associated with
      cortical vessels is judged to be subcellular. Light microscopic results suggest
      the extracellular pathways into the brain available to blood-borne native HRP do
      not represent predominant routes of entry for blood-borne WGA-HRP.
      Ultrastructural analysis further suggests WGA-HRP is likely to undergo adsorptive
      transcytosis through cerebral endothelia from blood to brain via specific
      subcellular compartments within the endothelium. Entry of blood-borne I-WGA-HRP,
      but not of I-ALB, is stimulated with coinjected unlabeled WGA-HRP, suggesting the
      latter may enhance the adsorptive endocytosis of blood-borne I-WGA-HRP. With
      i.c.v. coinjection of I-WGA-HRP and I-ALB, I-WGA-HRP exists the brain more slowly
      than I-ALB. The brain to blood passage of I-WGA-HRP is nil with inclusion of
      unlabeled WGA-HRP, which does not alter the exist of I-ALB. Adsorptive
      endocytosis of i.c.v. injected WGA-HRP appears restricted largely to cells lining
      the ventricular cavities, e.g., ependymal and choroid plexus epithelia. In
      summary, the data suggest that the bidirectional rates of passage between brain
      and blood for native HRP are comparable to those for albumin.

PMID- 7514656
TI  - Endodontically treated teeth: a summary of restorative concerns.
AB  - Endodontically treated teeth can be successfully used as abutments to support
      prostheses, both fixed and removable, if they are properly selected and restored.
      Selection and restoration criteria are presented.

PMID- 7514658
TI  - The restoration of endodontically treated teeth.

PMID- 7514657
TI  - Use of radicular attachments with endodontically treated teeth.
AB  - An extension of conventional overdenture philosophy with the use of radicular
      attachments in endodontically treated teeth can be used to improve stability,
      reduce bony resorption and proprioception and augment retention. However,
      radicular attachments are not appropriate in all cases. Indications,
      requirements, advantages and disadvantages of this type of prosthesis are
      provided.

PMID- 7514660
TI  - Confronting our Achilles' heel.

PMID- 7514659
TI  - Post cavity preparation and canal-retained post restoration: the restorative
      endodontic relationship.

PMID- 7514661
TI  - Analysis of cytokine receptor messenger RNA expression in human glioblastoma
      cells and normal astrocytes by reverse-transcription polymerase chain reaction.
AB  - To elucidate which cytokine receptors may be expressed by human glioblastoma and
      normal astrocytic cells, the presence of messenger ribonucleic acid (RNA) for a
      number of cytokine receptors was examined in 16 glioblastoma cell lines and adult
      and fetal astrocytes. A complementary deoxyribonucleic acid copy of total RNA was
      synthesized and amplified with specific primers using the polymerase chain
      reaction method. The receptors studied were interleukin (IL)-1 receptor type I
      (IL-1RI) and type II (IL-1RII), p75 and p55 tumor necrosis factor (TNF) receptors
      (p75TNFR and p55TNFR), interferon (IFN)-alpha/beta and -gamma receptors (IFN
      alpha/beta R and IFN-gamma R), granulocyte-macrophage (GM) colony-stimulating
      factors receptor alpha subunit (GM-CSFR), G-CSF receptor (G-CSFR), M-CSF receptor
      (c-fms, M-CSFR), stem cell factor receptor (c-kit, SCFR), IL-6 receptor (IL-6R),
      and IL-8 receptor (IL-8R). Transcripts for IL-1RI, p55TNFR, IFN-alpha/beta R, and
      IFN-gamma R were present in all cell lines. The presence of IL-1RII, p75TNFR, GM
      CSFR, M-CSFR, SCFR, IL-6R, and IL-8R was identified in 13, eight, seven, eight,
      14, three, and one cell lines, respectively. Normal astrocytes were positive for
      IL-1RI, p75TNFR, p55TNFR, IFN-alpha/beta R, IFN-gamma R, M-CSFR, and SCFR,
      showing a similarity to glioblastoma cells. Expression of IL-1RII was observed in
      adult astrocytes but not in fetal astrocytes. Furthermore, gene expression was
      assessed in normal brain tissue and 11 glioblastoma tissue specimens. The normal
      brain tissue expressed IL-1RI, IL-1RII, IFN-alpha/beta R, M-CSFR, and SCFR. Of
      the 11 glioblastoma tissue specimens, IL-1RI was positive in 11, IL-1RII in 10,
      p75TNFR in nine, p55TNFR in nine, IFN-alpha/beta R in 10, IFN-gamma R in 10, GM
      CSFR in two, G-CSFR in three, IL-8R in eight, and M-CSFR and SCFR in 11. These
      expressions were consistent with those in the cell lines, except for IL-8R. It is
      concluded that glioblastoma cells and normal astrocytes express a similar set of
      cytokine receptor genes in vitro and in vivo. Possible autocrine loops are
      suggested for IL-1 alpha/IL-1RI, TNF-alpha/p55TNFR, IFN-beta/IFN-alpha/beta R, M
      CSF/M-CSFR, and SCF/SCFR in glioblastomas.

PMID- 7514662
TI  - Polymorphous low-grade adenocarcinoma of the oral cavity: report of two cases.

PMID- 7514663
TI  - [Development of the research in the field of histamine release].
AB  - Histamine release from mast cells is intimately related with degranulation. When
      basic histamine releasers such as compound 48/80 were applied extracellularly to
      isolated rat mast cells by means of microelectrophoresis, localized degranulation
      was evoked near the tip of micropipet in a few seconds. In response to the second
      electrophoretic application at the opposite side of the membrane of the same mast
      cells, similar local degranulation was induced. This fact clearly indicates that
      local degranulation does not damage mast cells to the extent of blocking
      following degranulation. As intracellular electrophoretic application of compound
      48/80 caused a swelling of mast cell, although no degranulation was elicited.
      When antigen-antibody reaction was induced in a single rat mesentery mast cell by
      means of microelectrophoresis, the application of antigen was made
      extracellularly or intracellularly. At the site of extracellular application,
      localized degranulation and histamine release were evoked. Histamine release was
      evidenced by the disappearance of histamine fluorescence in the degranulated
      area. Neither degranulation nor histamine release was induced by intracellular
      application of antigen. In freeze-fracture electronmicroscopy of the resting rat
      mast cells, intra-membrane particles (IMPs) were randomly distributed on the
      plasma membrane. When sensitized cells were exposed to antigen, IMPs were
      markedly dispersed so as to surround bulging regions of the membrane elicited by
      swollen granules. As the particles gathered at the periphery of the bulges,
      actually no particle was seen on the protuberant region. When rat mast cells
      loaded with quin 2 were exposed compound 48/80 in a Ca-free medium, a marked
      increase of quin 2 fluorescence was noticed, indicating that Ca2+ was released
      from intracellular Ca store. The binding of 45Ca was at its peak in the fractions
      where the highest activity of glucose-6-phosphatase, a marker enzyme for the
      endoplasmic reticulum, when organelles of mast cells were fractionated. This may
      indicate that intracellular Ca store is endoplasmic reticulum. It has been shown
      that microfilaments, and microtubules play some important roles in histamine
      release from rat mast cells. When permeabilized mast cells were stimulated with
      Ca2+, a translocation of protein kinase C from cytosol to membrane fraction was
      observed. This leads to phosphorylation of vimentin, one of intermediate
      filaments. In membrane skeletons of rat mast cells, alpha- and beta-fodrin,
      ankyrin and actin were found by means of western blotting analysis. It was
      supposed that membrane skeleton may be useful as a barrier between the plasma
      membrane and the granule membrane.

PMID- 7514664
TI  - Voltage-dependent potassium channels in activated rat microglia.
AB  - 1. Voltage-dependent currents of untreated (proliferating) and lipopolysaccharide
      (LPS)-treated rat microglial cells in culture were recorded using the whole-cell
      patch-clamp technique. 2. Membrane potentials showed prominent peaks at -35 mV
      and -70 mV. Membrane potentials of LPS-treated cells alternated between the two
      values. This may be due to a negative slope region of the I-V relation resulting
      in two zero current potentials. 3. From a holding potential of -70 mV,
      hyperpolarizing steps evoked an inwardly rectifying current both in proliferating
      and in LPS-treated cells, while depolarizing steps below -50 mV evoked an
      outwardly rectifying current only in LPS-treated microglia. The currents were K+
      selective, as indicated by their reversal potential of approximately 0 mV in
      symmetric K+ concentrations (150 mM both intra- and extracellularly) and the
      reversal potential of the outward tail currents of approximately -90 mV at a
      normal extracellular K+ concentration (4.5 mM). 4. The activation of the outward
      current could be fitted by Hodgkin-Huxley-type n4 kinetics. The time constant of
      activation depended on voltage. 5. The inactivation of the inward and outward
      currents could be fitted by a single exponential. The time constant of the inward
      current inactivation was dependent on voltage, whereas the time constant of the
      outward current inactivation was virtually independent of voltage, except near
      the threshold of activation. Recovery of the outward from inactivation was slow
      and could be fitted by two exponentials. Responses to depolarizing steps were
      stable at 0.125 Hz, but greatly decreased from the first to the second pulse at 1
      Hz. 6. The inactivation of the inward, but not of the outward, current
      disappeared in a low Na(+)-containing medium (5 mM). The inward current was
      selectively inhibited by extracellular Cs+ and Ba2+. The outward current was
      selectively inhibited by Cd2+, 4-aminopyridine and charybdotoxin. Replacement of
      intracellular K+ by an equimolar concentration of Cs+, and the extracellular
      application of tetraethylammonium and quinine inhibited both currents. 7. An
      increase of extracellular Ca2+ from 2 to 20 mM resulted in outwardly rectifying
      K+ channels activating at more positive potentials. Omission of Ca2+ from the
      extracellular medium had the opposite effect. When the intracellular free Ca2+
      was increased from 0.01 to 1 microM, the outward current amplitudes were
      depressed. The Ca2+ ionophore A23187 had a similar effect. 8. LPS-treated
      microglial cells possess inwardly and outwardly rectifying K+ channels. The
      physiological and pharmacological characteristics of these two channel
      populations are markedly different.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514666
TI  - Facilitatory effect of docosahexaenoic acid on N-methyl-D-aspartate response in
      pyramidal neurones of rat cerebral cortex.
AB  - 1. The effect of docosahexaenoic acid (DHA) on N-methyl-D-aspartic acid (NMDA)
      responses in the presence of glycine was investigated in pyramidal neurons
      acutely dissociated from rat cerebral cortex in whole-cell and single channel
      configurations. 2. DHA potentiated the NMDA-induced response but reduced the non
      NMDA (kainate-induced) response in a concentration-dependent manner at a holding
      potential of -60 mV under voltage-clamp conditions. 3. Arachidonic acid (AA) also
      potentiated the NMDA-induced response in a manner similar to DHA. Oleic acid
      caused a slight potentiation. However, other polyunsaturated and saturated fatty
      acids had no such effects. 4. The facilitatory action of DHA on the NMDA-induced
      response was not affected by adding inhibitors of cyclo-oxygenase, lipoxygenase
      or phospholipase A2, suggesting that DHA may exert its facilitatory effect
      directly on the NMDA receptor. 5. The facilitatory action of DHA was observed in
      the presence of a saturating dose of NMDA. Moreover, a detailed analysis of the
      NMDA receptor-operated single channel currents revealed that, in the presence of
      DHA, the open probability of the channel increased without changing the
      conductance, indicating that DHA may act by binding directly to a novel site on
      the NMDA receptor or by altering the lipid environment of the NMDA receptor and
      thereby potentiating the response to NMDA. 6. The results are discussed in terms
      of the possibility that DHA may play an important role in the genesis of long
      term potentiation, at least that involving the activation of NMDA receptors.

PMID- 7514665
TI  - Benzodiazepine and beta-carboline regulation of single GABAA receptor channels of
      mouse spinal neurones in culture.
AB  - 1. The effects of the benzodiazepine receptor agonist, diazepam (DZ), and the
      inverse agonist, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate
      (DMCM), on gamma-aminobutyric acid (GABAA) receptor single channel currents were
      characterized. Outside-out patches were obtained from somata of cultured mouse
      spinal cord neurones and voltage clamped at -75 mV (ECl = 0 mV). 2. GABA (2
      microM) alone or with DZ (20-1000 nM) or DMCM (20-100 nM) was applied to patches
      by pressure ejection from blunt micropipettes. DZ enhanced GABAA receptor
      currents with an inverted U-shaped concentration-response curve. Mean steady
      state currents were increased by low concentrations of DZ (20-50 nM). At higher
      concentrations of DZ, the enhancement was diminished. Mean steady-state currents
      were decreased by DMCM at all concentrations. 3. GABAA receptor channels opened
      most frequently to a 27 pS main conductance level and less frequently to a 19 pS
      subconductance level. Neither DZ nor DMCM altered the proportion of time spent at
      either of the conductance levels. The kinetic properties of the main conductance
      level were studied. 4. Neither DZ nor DMCM altered the mean GABAA receptor
      channel open or burst durations. Sums of three exponential functions were
      required to fit best open and burst duration-frequency histograms for GABA alone
      or with DZ or DMCM. No significant changes in the three time constants or areas
      of the three exponential functions for open or burst duration histograms were
      produced by DZ or DMCM. 5. With increasing concentrations of DZ up to 50 nM, GABA
      evoked an increased frequency of channel openings and bursts. With higher DZ
      concentrations, the magnitudes of the increase in channel opening and burst
      frequencies were reduced. At all concentrations of DMCM, GABA evoked a decreased
      frequency of channel openings and bursts. 6. Closed duration-frequency histograms
      for GABA alone or with DZ or DMCM were best fitted by sums of at least six
      exponential functions. The three shortest closed duration time constants were
      unchanged by DZ or DMCM. The three longest closed duration time constants were
      altered by DZ and DMCM, consistent with alterations in opening frequency. 7. DZ
      increased and DMCM decreased steady-state GABAA receptor current by increasing or
      decreasing channel opening frequency without altering mean channel open duration.
      We propose that DZ and DMCM alter GABAA receptor current by acting reciprocally
      to increase or decrease only, respectively, the apparent agonist association rate
      at the first of two proposed GABA binding steps without altering channel
      gating.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514667
TI  - A comparison of non-NMDA receptor channels in type-2 astrocytes and granule cells
      from rat cerebellum.
AB  - 1. Patch-clamp recording methods have been used to compare the pharmacological
      properties and single-channel characteristics of non-NMDA receptor channels in
      cerebellar type-2 astrocytes and granule cells. 2. In type-2 astrocytes whole
      cell concentration-response curves for glutamate, quisqualate, AMPA and kainate
      gave EC50 values of 5.8, 3.8, 7.6 and 160 microM and Hill slopes of 1.65, 1.18,
      1.64 and 1.65, respectively, resembling estimates for granule cell receptors. 3.
      The non-NMDA receptor antagonists CNQX and diCl-HQC (see Methods) inhibited whole
      cell kainate currents in both cell types. The IC50 for CNQX antagonism of the
      kainate response was 536 nM in type-2 astrocytes, and 500 nM in granule cells.
      The IC50 for diCl-HQC was 3.5 microM in astrocytes and 3.7 microM in granule
      cells. 4. CNQX acted as a competitive antagonist of whole-cell kainate responses
      in type-2 astrocytes and granule cells giving Schild plots with a slope near 1.
      The equilibrium constant, K, for CNQX binding was 524 nM in astrocytes and 489 nM
      in granule cells. 5. Quisqualate and AMPA responses showed rapid desensitization
      in type-2 astrocytes with a ratio of steady-state to peak response of 0.09.
      Concanavalin A reduced this desensitization. 6. Non-NMDA channels in type-2
      astrocytes and granule cells showed a low permeability to Ca2+ ions with a
      reversal potential, for kainate-activated whole-cell currents in isotonic Ca2+,
      of approximately -25 mV for astrocytes and -45 mV for granule cells. 7. Outside
      out patches from type-2 astrocytes exhibited a range of single-channel
      conductances that were superficially similar to the glutamate-activated
      conductances in granule cells. However, the type-2 astrocytes were devoid of NMDA
      receptors, hence all of these conductances originated from non-NMDA channels.
      Their slope conductances were approximately 11, 21, 32, 42 and 52 pS. Amplitudes
      were verified with mean low-variance plots and single-channel current-voltage
      curves, which were linear. 8. There was also evidence of lower conductance
      kainate-activated channels in astrocyte patches. From noise analysis their
      estimated mean conductance was 1.9 pS, as described for the 'low-conductance'
      type kainate responses in cerebellar neurones. 9. Apparent open times, shut times
      and burst lengths of AMPA-activated (3-10 microM) channels were examined in
      patches from type-2 astrocytes, and kinetic properties of the 40 and 50 pS levels
      were compared with the lower levels. 10. Our results indicate some marked
      pharmacological similarities between non-NMDA receptor channels in type-2
      astrocytes and granule cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514668
TI  - Resistance monitoring in Culex pipiens (Diptera: Culicidae) from central-eastern
      France.
AB  - Insensitive acetylcholinesterase (AceR) and five over-produced esterases (A1, A2
      and B2, and A4 and B4) involved in detoxification are responsible for resistance
      to organophosphorous insecticides (OPs) in Culex pipiens L. from the Rhone-Alpes
      region, where C. pipiens control is mainly accomplished with the OPs temephos and
      chlorpyrifos using 0.15 mg/liter doses. The strong linkage disequilibria observed
      between esterases A1 and Est-20(0.64), esterases A4 and B4, and esterases A2 and
      B2 indicate that these genes were introduced in the Rhone-Alpes region. AceR and
      esterase A1, which appeared in the south of France 3 yr before the start of
      mosquito control in Rhone-Alpes, had the highest frequencies. All resistant
      genotypes were shown to be killed by 0.15 mg/liter temephos in natural breeding
      sites, but not by 0.15 mg/liter chlorpyrifos. These results are discussed in
      relation with mosquito control strategies.

PMID- 7514669
TI  - Open states of nuclear envelope ion channels in cardiac myocytes.
AB  - Prevalent nucleocytoplasmic transport theory views flow of monoatomic ions as
      completely unrestricted, resulting from the presence of large diameter pore
      complexes (NPCs) that perforate, but hold together, the two separate membranes of
      the nuclear envelope (NE). However, three lines of investigations indicate that,
      at least in some cell types, monoatomic ion flow is restricted. (i) Patch clamp
      reveals quantized, ion channel-like activity in several NE preparations; activity
      thought to result from nuclear ion channels (NICs) connected to NPCs. (ii)
      Ratiometric fluorescence microscopy demonstrates that ions, as well as small
      molecules relevant to signal transduction, do distribute as if there is a NE
      barrier. (iii) Electron microscopy shows that NPCs contain material that behaves
      like a plug. NICs' large conductance (up to 1,000 pS) makes them a major
      determinant of nuclear ion concentrations which, in turn, influence nuclear
      processes. Therefore, NICs are an important modulating force of gene and
      transcriptional activities--two major determinants of gene expression. As nuclear
      processes may take from seconds (e.g., signaling) to minutes (e.g.,
      transcription), the time the channels dwell in the ion-conducting open state is
      relevant to understanding NICs' role in nuclear function. Consequently, dwell
      times and lifetimes of open NIC states were studied in 61 patch-clamped adult
      mouse cardiac myocyte nuclei. Upon voltage stimulation, NICs opened to main
      states of large conductance (281 +/- 198 pS, range = 120-490 pS, n = 55) and wide
      range mean dwell-times (approximately 100 msec, 1-10 sec, and min). Closed states
      (0 pS) also had widely distributed mean dwell-times (approximately 100 msec, 1-10
      sec, and min). Putative open substates (37 +/- 11 pS, range = 25-50, pS, n = 6)
      of high bursting frequency (< 1 msec) were observed without intervening main
      states (approximately 5% of patches). Fast (approximately 0.1 msec) and slow
      (approximately 10 msec) state-transitions were also detected. These observations
      suggest a role of NICs in mediating cytoplasmic signal control of cardiomyocyte
      gene expression.

PMID- 7514673
TI  - Nitric oxide synthase inhibition aggravates intestinal microvascular
      vasoconstriction and hypoperfusion of bacteremia.
AB  - Nitric oxide (NO) is an important hemodynamic mediator of sepsis; however, its
      visceral microcirculatory effects are largely unknown. To determine the role of
      systemic nitric oxide synthase (NO-S) inhibition on the microcirculation of the
      small intestine (SI), an intact loop of SI was exteriorized from decerebrate rats
      into a controlled tissue bath. Videomicroscopy was used to measure arteriolar
      diameters (A1, A3) and optical Doppler velocimetry was used to quantitate flow.
      In nonbacteremic controls inhibition of NO-S by N omega-nitro-L-arginine methyl
      ester (L-NAME; 1 mg/kg IV) caused vasoconstriction (A1 = -7%; A3 = -24% baseline
      values) and reduced A1 flow by 26%. Bacteremic controls received 10(9)
      Escherichia coli IV, which resulted in arteriolar constriction and hypoperfusion
      (A1 = -16%; A3 = -21%; A1 flow = -44%), despite increased cardiac output (+33%).
      Treatment of bacteremic rats with L-NAME corrected the increased cardiac output (
      3%), but exacerbated vasoconstriction (A1 = -24%; A3 = -27%) and did not improve
      A1 flow (-49%). These data indicate that (1) NO mediates basal microvascular tone
      of the SI; (2) hyperdynamic bacteremia causes arteriolar constriction and
      hypoperfusion of the SI; and (3) although systemic NO-S inhibition normalizes
      cardiac output and increases blood pressure, it aggravates vasoconstriction in
      the SI and does not improve hypoperfusion.

PMID- 7514670
TI  - Alpha-latrotoxin channels in neuroblastoma cells.
AB  - The changes in ionic permeability induced by the application of alpha-latrotoxin
      to NG108-15 neuroblastoma x glioma cells were examined using the nystatin
      perforated-patch technique for whole-cell recording. Complex single channel
      activity appeared in the plasmalemmas after delays that ranged from 1-20 min in
      Krebs' solution. The conductance of a channel fluctuated among at least three
      broad, approximately equispaced bands, the maximum conductance being about 300
      pS, and the reversal potential approximately 0 mV. The channels were permeable to
      Na+, K+, Ca2+ and Mg2+, poorly permeable to glucosamineH+ and Cl-, and were
      blocked by La3+. The channels stayed fully open in Ca(2+)-free solutions with 4
      mM Mg2+, in solutions with no divalent cations and in solutions with 2 mM Ca2+
      and 96 mM Mg2+. They opened infrequently if both internal and external Cl- were
      replaced by glutamate-. If alpha-latrotoxin opened similar channels in nerve
      terminals, the flux of ions through them could account for the massive release of
      neurotransmitter induced by the toxin.

PMID- 7514671
TI  - Gonadotropin-producing benign cystic teratoma simulating a ruptured ectopic
      pregnancy.
AB  - Benign cystic teratomas are asymptomatic in many cases. There are some reports of
      production of thyroid-stimulating hormone, estrogen, testosterone, and prolactin
      by these tumors. This article reports a patient in whom a twisted cystic teratoma
      simulated ruptured ectopic pregnancy by beta human chorionic gonadotropin
      production and hemorrhage into the peritoneal cavity.

PMID- 7514672
TI  - Effect of inhibiting leukocyte integrin (CD18) and selectin (L-selectin) on
      susceptibility to infection with Pseudomonas aeruginosa.
AB  - Leukocyte (WBC) adherence to endothelial cells has been implicated in the
      pathogenesis of microvascular injury. The process of leukocyte adherence is
      mediated by both the integrin and selectin families of molecules, and their
      interaction with specific endothelial ligands. Antibodies directed against the
      leukocyte integrin CD18 and L-selectin have been developed and functionally
      inhibit leukocyte adherence in models of inflammatory injury. We asked the
      question: Does inhibition of leukocyte adherence by administration of monoclonal
      antibody directed against either CD18, integrins (R15.7, R7.1) or against L
      selectin (DREG 200) increase susceptibility to infection? New Zealand white
      rabbits were shaved and injected subcutaneously on their dorsum with Pseudomonas
      aeruginosa (ATCC#27853) at two sites each of 10(8) and 10(7) colony forming
      units. Animals were monitored with daily determination of weight, temperature,
      WBC counts, hematocrit, and killed at 1 week for determination of abscess
      formation. There were four blinded experimental groups: (1) Saline (2 mL/kg); (2)
      DREG 200 (2 mg/kg); (3) R7.1 (2 mg/kg); or (4) R15.7 (2 mg/kg). At the 10(7) and
      10(8) injection sites the R15.7 group had an increased rate and size of abscess
      formation compared with controls. The R7.1 group had an increased rate at the
      10(8) injection site. There was no significant difference in the percentage of
      the abscess formation or mean area between the controls and DREG 200-treated
      groups. We conclude that giving antibody to CD18 increased susceptibility to
      infection while giving antibody to L-selectin does not.

PMID- 7514674
TI  - VCAM-1 is a receptor for encephalomyocarditis virus on murine vascular
      endothelial cells.
AB  - Murine VCAM-1 has been identified as a receptor for the D variant of
      encephalomyocarditis (EMC-D) virus on vascular endothelial cells from the heart.
      Monoclonal antibodies to VCAM-1 inhibited infection and lysis of endothelial
      cells with EMC-D virus. CHO cells transfected with the VCAM-1 gene were
      susceptible to EMC-D virus lysis, while control CHO cells transfected with the
      ELAM-1 gene were resistant. Similarly, 35S-labeled EMC-D virus bound to CHO-VCAM
      cells, and binding was inhibited with anti-VCAM-1 antibodies. Little or no
      radiolabeled virus bound to CHO-ELAM-1 cells.

PMID- 7514675
TI  - Alteration of V3 loop context within the envelope of human immunodeficiency virus
      type 1 enhances neutralization.
AB  - Neutralization of a chimeric human immunodeficiency virus (HIV) type 1,
      containing the V3 loop of the MN isolate substituted within the HXB2 envelope,
      was enhanced up to 20-fold compared with the HXB2 or MN parental isolates by
      human HIV-positive sera. MN V3 loop-specific monoclonal antibodies were better
      able to recognize the chimeric virus compared with MN, staining a greater
      percentage of infected cells and exhibiting slight increases in relative affinity
      with a concomitant increase in neutralization titer. Competition analysis
      revealed that enhanced neutralization by human HIV-positive sera of the chimera
      was attributable in some cases to better reactivity with the linear V3 loop
      epitope but in others to conformational loop epitopes or previously cryptic or
      poorly recognized epitopes outside the loop region. Mice primed with a vaccinia
      virus-chimeric envelope recombinant and boosted with gp160 developed a spectrum
      of antibodies different from that of mice similarly immunized with HXB2 or MN
      recombinants or that of naturally infected humans. The chimeric envelope elicited
      antibodies with enhanced binding to the native MN V3 loop; however, the sites
      seen by the BALB/c mice were not neutralizing epitopes. Nevertheless, similar to
      the observations made with use of human sera, the chimeric virus was more readily
      neutralized by all of the immune mouse sera, an effect apparently mediated by non
      V3 loop epitopes. These studies illustrate that not only the V3 loop sequence and
      conformation but also its context within the viral envelope influence
      neutralization.

PMID- 7514676
TI  - Protection against lethal lymphocytic choriomeningitis virus (LCMV) infection by
      immunization of mice with an influenza virus containing an LCMV epitope
      recognized by cytotoxic T lymphocytes.
AB  - The reverse genetics system has made it possible to modify the influenza virus
      genome. By this method, we were able to assess influenza virus as a vaccine
      vector for protecting BALB/c mice against otherwise lethal lymphocytic
      choriomeningitis virus (LCMV) infection. A single dose of influenza virus
      [A/WSN/33 (H1N1)] bearing a cytotoxic T-lymphocyte-specific epitope of the LCMV
      nucleoprotein (residues 116 to 127) in the neuraminidase stalk protected mice
      against LCMV challenge for at least 4 months. The immunity was mediated by
      cytotoxic T lymphocytes and was haplotype specific, indicating that the observed
      protective response was solely a consequence of prior priming with the H-2d LCMV
      nucleoprotein epitope expressed in the recombinant influenza virus. We also found
      that as many as 58 amino acids could be inserted into the neuraminidase stalk
      without loss of viral function. These findings demonstrate the potential of
      influenza virus as a vaccine vector, with the neuraminidase stalk as a repository
      for foreign epitopes.

PMID- 7514678
TI  - Mapping and characterization of antigenic epitopes and the nucleic acid-binding
      domains of the VP6 protein of bluetongue viruses.
AB  - Heterologously expressed VP6 and truncated VP6 proteins of bluetongue virus (BTV)
      serotype 11 purified to near homogeneity were used for structure and function
      analyses. The yield of the expressed VP6 was host cell dependent. Six antigenic
      epitopes of VP6 of BTV were identified and mapped by immunoblot analyses and
      enzyme-linked immunosorbent assay with oligoclonal antibodies. These determinants
      were surface accessible and conserved among the cognate VP6 proteins of five U.S.
      BTV serotypes. The amino acid sequences and sizes of these six antigenic epitopes
      were determined, and their precise locations were also mapped and confirmed by
      deletion analyses. The nucleic acid binding activities of VP6, confirmed by
      electrophoretic mobility shift assay, were concentration dependent. The binding
      activities and affinities of the purified expressed VP6 protein towards double
      stranded RNA and double-stranded DNA were similar. Two domains of VP6,
      corresponding to three of the six antigenic epitopes, were responsible for the
      nucleic acid binding activities and have been mapped within 28 amino acids near
      the middle and 11 residues near the carboxyl terminus of VP6 by electrophoretic
      mobility shift assay and deletion mutant analyses. Synthetic oligopeptides
      corresponding to these three regions also exhibited similar concentration
      dependent nucleic acid binding activities.

PMID- 7514677
TI  - Primary pulmonary cytotoxic T lymphocytes induced by immunization with a vaccinia
      virus recombinant expressing influenza A virus nucleoprotein peptide do not
      protect mice against challenge.
AB  - The nucleoprotein (NP) of influenza A virus is the dominant antigen recognized by
      influenza virus-specific cytotoxic T lymphocytes (CTLs), and adoptive transfer of
      NP-specific CTLs protects mice from influenza A virus infection. BALB/c mouse
      cells (H-2d) recognize a single Kd-restricted CTL epitope of NP consisting of
      amino acids 147 to 155. In the present study, mice were immunized with various
      vaccinia virus recombinant viruses to examine the effect of the induction of
      primary pulmonary CTLs on resistance to challenge with influenza A/Puerto
      Rico/8/34 virus. The minigene ESNP(147-155)-VAC construct, composed of a signal
      sequence from the adenovirus E3/19K glycoprotein (designated ES) and expressing
      the 9-amino-acid NP natural determinant (amino acids 147 to 155) preceded by an
      alanine residue, a similar minigene NP(Met 147-155)-VAC lacking ES, and a full
      length NP-VAC recombinant of influenza virus were analyzed. The two minigene NP
      VAC recombinants induced a greater primary pulmonary CTL response than the full
      length NP-VAC recombinant. However, NP-specific CTLs induced by immunization with
      ESNP(147-155)-VAC did not decrease peak virus titer or accelerate clearance of
      virus in the lungs of mice challenged intranasally with A/PR/8/34. Furthermore,
      NP-specific CTLs induced by immunization did not protect mice challenged
      intranasally with a lethal dose of A/PR/8/34. Sequence analysis of the NP CTL
      epitope of A/PR/8/34 challenge virus obtained from lungs after 8 days of
      replication in ESNP(147-155)-VAC-immunized mice showed identity with that of the
      input virus, demonstrating that an escape mutant had not emerged during
      replication in vivo. Thus, in contrast to adoptively transferred CTLs, pulmonary
      NP-specific CTLs induced by recombinant vaccinia virus immunization do not have
      protective in vivo antiviral activity against influenza virus infection.

PMID- 7514680
TI  - Antigenic structure of envelope glycoprotein E1 of hog cholera virus.
AB  - Envelope glycoprotein E1 (gp51 to gp54) is the most antigenic protein of hog
      cholera virus or classical swine fever virus (CSFV). Four antigenic domains, A to
      D, have been mapped on E1 with a panel of monoclonal antibodies (MAbs) raised
      against CSFV strain Brescia. The boundaries of these domains have been
      established by extensive studies on binding of MAbs to transiently expressed
      deletion mutants of E1 (P. A. van Rijn, E. J. de Meijer, H. G. P. van Gennip, and
      R. J. M. Moormann, J. Gen. Virol. 74:2053-2060, 1993). In this study, we used
      neutralizing MAbs of domains A, B, and C to isolate MAb-resistant mutants (MAR
      mutants) of CSFV strain Brescia and Chinese vaccine strain ("C"). The E1 genes of
      MAR mutants were cloned in a eukaryotic expression vector, and the effects of MAR
      mutations on epitopes were studied with a panel of 19 MAbs by immunostaining of
      COS1 cells transiently expressing these mutant E1s. Except for the MAR mutation
      Cys-->Arg at position 792, which abolished binding of all MAbs of domains A and
      D, amino acid substitutions affected only MAbs belonging to the same domain as
      the MAb used to select the MAR mutant. However, a MAR mutation in a particular
      domain did not per se abolish binding of all MAbs recognizing that domain.
      Furthermore, MAR mutants possessed conservative as well as nonconservative amino
      acid substitutions. To investigate the significance of a secondary structure for
      the binding of MAbs, all cysteine residues in the N-terminal antigenic part of E1
      were mutated to serine. We found that the cysteines at positions 693 and 737 were
      essential for binding by MAbs of domains B and C, whereas those at positions 792,
      818, 828, and 856 appeared to be essential for the binding of most MAbs of
      domains A and D. These results fully comply with the previously proposed two-unit
      structure of the N-terminal half of E1. One unit consists of antigenic domains B
      and C, whereas the other unit consists of the highly conserved domain A and
      domain D. We conclude that the first six cysteines are critical for the correct
      folding of E1. A model of the antigenic structure of E1 is presented and
      discussed.

PMID- 7514679
TI  - Products of the porcine group C rotavirus NSP3 gene bind specifically to double
      stranded RNA and inhibit activation of the interferon-induced protein kinase PKR.
AB  - The porcine group C rotavirus (Cowden strain) NSP3 protein (the group C
      equivalent of the group A gene 7 product, formerly called NS34) shares homology
      with known double-stranded RNA-binding proteins, such as the interferon-induced,
      double-stranded RNA-dependent protein kinase PKR. A clone of NSP3, expressed both
      in vitro and in COS-1 cells, led to the synthesis of minor amounts of a product
      with an M(r) of 45,000 (the expected full-length M(r) of NSP3) and major amounts
      of products with M(r)s of 38,000 and 8,000. Restriction enzyme digestion analysis
      prior to expression in vitro and amino-terminal sequence analysis suggest that
      the products with M(r)s of 38,000 and 8,000 are cleavage products of the protein
      with an M(r) of 45,000. The full-length protein and the product with an M(r) of
      8,000, both of which contain the motif present in double-stranded RNA-binding
      proteins, bound specifically to double-stranded RNA. The products with M(r)s of
      45,000 and 8,000 were also detected in Cowden strain-infected MA104 cells. NSP3
      products expressed in COS-1 cells were capable of inhibiting activation of the
      double-stranded RNA-dependent protein kinase similar to other double-stranded RNA
      binding proteins, and NSP3 products expressed in HeLa cells were capable of
      rescuing the replication of an interferon-sensitive deletion mutant of vaccinia
      virus.

PMID- 7514681
TI  - Localization of rotavirus VP4 neutralization epitopes involved in antibody
      induced conformational changes of virus structure.
AB  - We previously characterized three neutralization-positive epitopes (NP1 [1a and
      1b], NP2, and NP3) and three neutralization-negative epitopes on the simian
      rotavirus SA11 VP4 with 13 monoclonal antibodies (MAbs). Conformational changes
      occurred as a result of the binding of NP1 MAbs to the SA11 spike VP4, and
      enhanced binding of all neutralization-negative MAbs was observed when NP1 MAbs
      bound VP4 in a competitive MAb capture enzyme-linked immunosorbent assay. To
      further understand the structure and function of VP4, we have continued studies
      with these MAbs. Electron microscopic and sucrose gradient analyses of SA11-MAb
      complexes showed that triple-layered viral particles disassembled following
      treatment with NP1b MAbs 10G6 and 7G6 but not following treatment with NP1a MAb
      9F6, NP2 MAb 2G4, and NP3 MAb 23. Virus infectivity was reduced approximately 3
      to 5 logs by the NP1b MAbs. These results suggest that NP1b MAb neutralization
      occurs by a novel mechanism. We selected four neutralization escape mutants of
      SA11 with these VP4 MAbs and characterized them by using plaque reduction
      neutralization assays, hemagglutination inhibition assays, and an antigen capture
      enzyme-linked immunosorbent assay. These analyses support the previous assignment
      of the NP1a, NP1b, NP2, and NP3 MAbs into separate epitopes and confirmed that
      the viruses were truly neutralization escape mutants. Nucleotide sequence
      analyses found 1 amino acid (aa) substitution in VP8* of VP4 at (i) aa 136 for
      NP1a MAb mutant 9F6R, (ii) aa 180 and 183 for NP1b MAb mutants 7G6R and 10G6R,
      respectively, and (iii) aa 194 for NP3 MAb mutant 23R. The NP1b MAb mutants
      showed an unexpected enhanced binding with heterologous nonneutralization MAb to
      VP7 compared with parental SA11 and the other mutants. Taken together, these
      results suggest that the NP1b epitope is a critical site for VP4 and VP7
      interactions and for virus stability.

PMID- 7514682
TI  - Poliovirus neutralization by antibodies to internal epitopes of VP4 and VP1
      results from reversible exposure of these sequences at physiological temperature.
AB  - Antisera were raised against peptide sequences that are normally internal in the
      poliovirus virion. These antisera contain neutralizing activity, but this
      neutralizing activity is dependent on coincubation of the virus and antisera at
      37 degrees C. Immunoprecipitation analyses demonstrate that the neutralization is
      due to exposure of these normally internal sequences at 37 degrees C and
      subsequent antibody binding. Exposure of these sequences is reversible. These
      data demonstrate that the poliovirus particle is a dynamic entity that is capable
      of undergoing conformational alterations at physiological temperatures. This
      conformational flexibility provides an explanation for earlier observations of
      virus neutralization by antibodies to internal epitopes which can be accommodated
      within the framework of existing models for antibody-mediated neutralization of
      viral infectivity. Analogies between the sequences which are reversibly exposed
      at 37 degrees C with those which are irreversibly exposed upon receptor binding
      suggest that the observed conformational dynamics also may play a role in cell
      entry.

PMID- 7514685
TI  - Outpatient transurethral resection of the prostate at a urological ambulatory
      surgery center.
AB  - Transurethral resection of the prostate has been the standard treatment for
      patients with benign prostatic hyperplasia, and it has traditionally required 2
      to 7 days of hospitalization. Since 1991 we performed outpatient transurethral
      resection of the prostate at a urological ambulatory surgery center on 125 select
      patients. Standard resection techniques were used with particular attention to
      hemostasis, since bladder irrigation was stopped before patients were discharged
      home. Transfer to a hospital was required for 3 patients because of hematuria, 1
      for fever and suspected bacteremia, and 1 for cardiac dysrhythmia. No patient
      required hospitalization after he was discharged from the ambulatory surgery
      center. Outpatient transurethral resection of the prostate can be performed
      safely with excellent patient satisfaction and cost-effectiveness. Alternative
      treatment modalities for benign prostatic hyperplasia should be evaluated against
      outpatient transurethral resection of the prostate before they are broadly
      embraced.

PMID- 7514683
TI  - Synergistic neutralization of human immunodeficiency virus type 1 by combinations
      of human monoclonal antibodies.
AB  - The ability of antibodies to the V3 region and the CD4-binding domain (CD4bd) of
      human immunodeficiency virus type 1 (HIV-1) to act in synergy to neutralize HIV
      has been demonstrated previously. However, synergy between antibodies to other
      HIV-1 epitopes has not been studied. We have used 21 combinations of human
      monoclonal antibodies (MAbs) directed against different epitopes of the gp120 and
      gp41 proteins of HIV-1 to evaluate their ability to act in synergy to neutralize
      HIV-1. Combinations of anti-V3 and anti-CD4bd antibodies, anti-V3 and anti-gp120
      C-terminus antibodies, anti-CD4bd and anti-C-terminus antibodies, anti-V3 and
      anti-gp41 antibodies, and anti-CD4bd and anti-gp41 antibodies were tested. Our
      results show that some, but not all anti-V3 antibodies can act in synergy with
      anti-CD4bd antibodies. In addition, for the first time, antibodies to the C
      terminus region have been found to act in synergy with the anti-CD4bd antibodies.
      Various anti-CD4bd MAbs also act in synergy when used together. The use of such
      cocktails of human MAbs for passive immunization against HIV-1 may prove to be
      important for therapy in postexposure settings and for prevention of maternal
      fetal transmission of the virus. The results also provide information on the
      types of antibodies that should be elicited by an effective vaccine.

PMID- 7514686
TI  - The influence of prostatic urethral anesthesia in overactive detrusor in patients
      with benign prostatic hyperplasia.
AB  - We examined the effects of prostatic urethral anesthesia on cystometrography in
      benign prostatic hyperplasia (BPH) patients with or without neurological
      disorders. Although cystometrography after anesthesia showed no disappearance of
      involuntary detrusor contraction, it did demonstrate significant increases in
      first sensation volume and maximum cystometric capacity in BPH patients without
      neurological diseases, as well as BPH patients with a history but no physical
      evidence of neurological disease. Furthermore, the bladder might be augmented
      more efficaciously in patients with involuntary detrusor contractions. No
      significant differences were found in first sensation volume or maximum
      cystometric capacity before and after anesthesia in patients without infravesical
      obstruction who had documented neurological disease with physical evidence. Our
      results demonstrated that prostatic urethral anesthesia can be used
      preoperatively in patients with infravesical obstruction to discriminate whether
      involuntary detrusor contractions are due to infravesical obstruction or to
      neurological disease.

PMID- 7514684
TI  - Cross-neutralizing activity against divergent human immunodeficiency virus type 1
      isolates induced by the gp41 sequence ELDKWAS.
AB  - Previously we identified the highly conserved amino acids Glu-Leu-Asp-Lys-Trp-Ala
      (ELDKWA) on the ecto-domain of gp41 as the epitope of a neutralizing monoclonal
      antibody (2F5) directed against human immunodeficiency virus type 1. In the
      present study, the sequence defining the epitope was introduced into the loop of
      antigenic site B of the influenza virus hemagglutinin. The resulting chimeric
      virus was able to elicit ELDKWA-specific immunoglobulins G and A in antisera of
      mice. Moreover, the distantly related human immunodeficiency virus type 1
      isolates MN, RF, and IIIB were neutralized by these antisera. These data suggest
      that this conserved B-cell epitope is a promising candidate for inclusion in a
      vaccine against AIDS. The results also show that influenza virus can be used to
      effectively present the antigenic structure of this B-cell epitope.

PMID- 7514687
TI  - Benign prostatic hyperplasia.

PMID- 7514689
TI  - Combining prostate specific antigen with cancer and gland volume to predict more
      reliably pathological stage: the influence of prostate specific antigen cancer
      density.
AB  - The serum prostate specific antigen (PSA) level was determined in 311 men with
      documented prostate cancer (stages T1cN0, T2N0 and T3N0) before bilateral pelvic
      lymphadenectomy and radical retropubic prostatectomy. The prostates were whole
      mounted, serially sectioned, and examined for cancer volume, capsular
      perforation, seminal vesicle invasion, lymph node involvement, Gleason grade,
      nuclear grade and nuclear deoxyribonucleic acid content. Median serum PSA level
      was significantly different between cancers that were organ confined, those that
      had capsular perforation or seminal vesicle invasion and those with positive
      lymph nodes (p < 0.001). Median serum PSA level was also significantly different
      between tumors with Gleason scores of less than 6 and those with higher Gleason
      scores (p < 0.001), and between tumors with greater than 30% of poorly
      differentiated cancer (Gleason primary grades 4 and 5) and those with 30% or less
      poorly differentiated cancer (p < 0.001). Bivariate analysis revealed that the
      strongest correlations of serum PSA level were with cancer volume (r = 0.56), per
      cent of poorly differentiated cancer (r = 0.42), positive surgical margins (r =
      0.39) and pathological stage (r = 0.38), for all p < 0.001. Multivariate analysis
      showed that cancer volume was the major contributor to serum PSA level. The
      derivative, PSA-cancer density (serum PSA times cancer volume divided by prostate
      volume), accounted for the effects of prostate volume and cancer volume on serum
      PSA. PSA-cancer density showed a significant correlation with pathological stage
      (r = 0.56), Gleason score (r = 0.53) and per cent of poorly differentiated cancer
      (r = 0.49, for all p < 0.001), and these correlations were significantly stronger
      than serum PSA level alone or PSA density (serum PSA divided by prostate volume;
      volume determined from tissue specimens) for all variables. These results
      indicate that preoperative serum PSA level has significant predictive value in
      determining tumor burden and pathological stage, and this predictive value is
      increased by accounting for cancer and gland volume with PSA-cancer density.

PMID- 7514688
TI  - Prostate specific antigen and gleason grade: an immunohistochemical study of
      prostate cancer.
AB  - Prostate cancer is histologically heterogeneous as reflected in the 5 patterns of
      the Gleason grading system. Gleason grade correlates with volume, extent and
      prognosis. Serum prostate specific antigen (PSA) levels also correlate with tumor
      volume but the degree to which grade correlates with PSA has not been precisely
      defined. To quantify this relationship further, we prepared maps of each grade of
      cancer in 86 radical prostatectomy specimens from patients with clinical stage T2
      cancer. The median per cent of the volume of cancer per prostate composed of
      grade 1 was 0%, while it was 1% for grade 2, 84% for grade 3, 5% for grade 4 and
      0% for grade 5. We stained 95 cancer foci (grades 1 to 5) in 40 of these
      specimens for PSA. The presence and intensity (0 to 3+) of staining in more than
      33,000 acini (or cells) correlated inversely with grade (p < 0.0001). Nearly all
      acini in grade 1 and most in grade 2 stained positive (2 to 3+) for PSA; 87% were
      positive but with less intensity in grade 3. While many grade 4 (79%) and grade 5
      (49%) cells were positive, the intensity of staining was weak. Serum PSA levels
      correlated with total tumor volume (r = 0.67) but serum PSA levels per cm.3 of
      cancer decreased with increasing grade (r = -0.24 and p < 0.02). These studies
      confirm the strong inverse correlation between Gleason grade and the PSA content
      of prostate cancer. Since more than 85% of grade 3 acini stained for PSA and
      grade 3 made up the largest portion (84%) of cancer, the predominant contributor
      to serum PSA levels from prostate cancer was Gleason grade 3. The other grades
      contribute relatively little to the serum PSA levels either because of the small
      volume (grades 1 and 2) or the diminished PSA content (grades 4 and 5).

PMID- 7514691
TI  - Effect of radiation therapy on detectable serum prostate specific antigen levels
      following radical prostatectomy: early versus delayed treatment.
AB  - Radiation therapy may be beneficial after radical prostatectomy in some patients
      with pathological stage C prostate cancer and in those with detectable
      postoperative prostate specific antigen (PSA) levels. A total of 64 men underwent
      postoperative radiation therapy following radical prostatectomy for pathological
      stage C disease (27), a detectable serum PSA level (11) or both conditions (26).
      Of the 27 men treated prophylactically for pathological stage C disease 18 (67%)
      had no evidence of recurrence after radiation within the first 6 months
      postoperatively (median followup 40 months, range 17 to 97). Of 22 men treated
      for delayed PSA elevation 15 (68%) currently are disease-free (median followup
      27.5 months, range 15 to 47). Of 15 men treated within the first 6 months after
      radical prostatectomy for persistently detectable PSA levels 8 (53%) had an
      initial decrease in PSA to undetectable levels but only 5 (33%) had a durable
      complete response (median followup 36 months, range 8 to 56). We conclude that
      patients with pathological stage C disease who are most likely to benefit from
      postoperative radiation therapy are those with initially undetectable
      postoperative PSA levels. We observed no striking difference in treatment outcome
      between early and delayed adjuvant radiation therapy.

PMID- 7514690
TI  - Serial prostatic biopsies in men with persistently elevated serum prostate
      specific antigen values.
AB  - The objective of this study was to determine the need for repeat prostatic
      biopsies in men whose initial biopsy results revealed no evidence of cancer or
      atypia. We evaluated 1,136 men who underwent 1 or more prostatic biopsies in a
      longitudinal prostate specific antigen (PSA) based prostate cancer screening
      study that called for biopsy if the serum PSA level was greater than 4.0 ng./ml.
      (Hybritech assay) and findings on rectal examination or ultrasonography were
      abnormal or suspicious for cancer. Of the 1,136 men who underwent prostatic
      biopsy 391 (34%) had prostate cancer on the initial biopsy. Of 427 men who had
      negative initial biopsy results, a persistent serum PSA level of greater than 4.0
      ng./ml. and abnormal rectal or ultrasound examination findings 82 (19%) had
      cancer on biopsy 2. Of 203 men with persistent abnormalities 16 (8%) had cancer
      on biopsy 3 and 6 of 91 (7%) had cancer on biopsy 4 or later. Thus, 96% of the
      cancers were detected through either biopsy 1 or 2. The median initial PSA level,
      followup PSA levels and the yearly rate of change in PSA were significantly
      greater in men whose cancer was detected compared with those of men whose cancer
      was not detected (6.4 versus 5.4 ng./ml., 7.4 versus 6.6 ng./ml. and 1.1 versus
      0.7 ng./ml. per year, respectively). There was a trend for a higher percentage of
      tumors detected through serial screening to be pathologically organ confined with
      those detected through initial screening (73% versus 62%, p = 0.07). We conclude
      that men with a persistently elevated serum PSA value after an initial negative
      prostatic biopsy should routinely undergo at least 1 repeat biopsy to exclude
      adequately the presence of detectable prostate cancer.

PMID- 7514692
TI  - The effect of pelvic radiation therapy on serum levels of prostate specific
      antigen.
AB  - To determine the effect of prostatic irradiation on the production of prostate
      specific antigen (PSA), serum PSA levels were measured in 36 men who received
      pelvic irradiation (45 to 65 Gy.) for nonprostatic malignancies, and compared
      with those of a control group of 79 men of comparable age without prostate cancer
      or prior pelvic irradiation identified from the records of the Massachusetts
      General Hospital internal physicians. The median PSA level was lower in the
      irradiated group than in the control group (0.65 versus 1.1 ng./ml.). Of the
      irradiated patients 47% had undetectable PSA levels versus 20% of the controls (p
      = 0.004, Fisher's exact test). A group of 27 prostate cancer patients who
      received up to 68 Gy. 8 to 16 years (median 10 years) previously and who remained
      clinically disease-free were also studied. The median PSA level was less than 0.5
      ng./ml. The proportion of patients with undetectable PSA levels was significantly
      higher than that of the controls (p < 0.001) but it was not significantly
      different from those irradiated for other pelvic cancers. Of those patients 67%
      had an undetectable PSA level and 78% had a level of less than 1 ng./ml. Our
      study suggests that radiation therapy results in a permanent decrease in PSA
      production by the prostate gland and that patients whose PSA values do not reach
      less than 1 ng./ml. following radical radiation therapy for prostate cancer are
      unlikely to be long-term clinical disease-free survivors.

PMID- 7514693
TI  - Prostate specific antigen.

PMID- 7514694
TI  - Where treatment may be necessary and possible.

PMID- 7514695
TI  - Re: Localized hyperthermia versus the sham procedure in obstructive benign
      hyperplasia of the prostate: a prospective randomized study.

PMID- 7514696
TI  - Granulocyte colony-stimulating factor produced by bladder carcinoma of a patient
      with leukemoid reaction did not affect proliferation of the tumor cells.
AB  - Bladder carcinoma associated with leukemoid reaction, though it rarely occurs, is
      considered highly malignant and has proved to produce granulocyte colony
      stimulating factor (G-CSF). Interest exists in whether G-CSF itself or G-CSF
      producing ability reflects the malignant potential of such a tumor, possibly
      through an autocrine mechanism. In a patient with invasive bladder carcinoma, we
      found that the tumor cells produced G-CSF responsible for a remarkable
      leucocytosis. However, we could not detect the rearrangement and amplification of
      the G-CSF gene nor the expression of G-CSF receptor in the tumor cells. Our
      immunohistological and molecular biological study failed to demonstrate a crucial
      role for G-CSF in mediating a growth advantage for the tumor.

PMID- 7514697
TI  - [Successful collection of peripheral blood stem cells mobilized by high-dose
      etoposide for patients with chemotherapy-resistant and/or poor prognostic
      testicular cancer].
AB  - Clinical effects of peripheral blood stem cell autotransplantation (PBSCT) after
      ultra high-dose chemotherapy were evaluated in patients with chemotherapy
      resistant and/or poor prognostic testicular cancer. Four patients with testicular
      cancer, who had high-risk malignancy, were treated with high-dose etoposide (500
      mg/m2 x 4 days) in order to collect peripheral blood stem cells. After the
      administration of high-dose etoposide, rG-CSF (250 micrograms/body) was
      administered from nadir state. Blood mononuclear cells were collected using a
      Fenwall CS-3000 blood cell separator. Fractions enriched for stem cells were
      obtained by discontinuous Percoll gradient centrifugation and were stored in
      liquid nitrogen using patient's sera and DMSO. The mean number of peripheral
      blood granulocyte-macrophage-colony-forming units (CFU-GM) collected by one
      apheresis was 22.3 x 10(5)/kg body weight. In addition, CFU-GM more than 2.0 x
      10(5)/kg body weight could be collected in each apheresis, which was though to be
      sufficient dosis to perform PBSCT in safe, based upon our previous studies. All
      the patients were treated by a combination of cisplatin (20 mg/m2 x 5 days),
      etoposide (100 mg/m2 x 5 days) and bleomycin (15 mg x 3 days). Three patients
      responded to BEP therapy and obtained a CR, however, remaining 1 patient failed
      to achieve CR, who was later treated by ultrahigh-dose chemotherapy including
      carboplatin (200 mg/m2 x 4 days), etoposide (250 mg/m2 x 4 days) and
      cyclophosphamide (50 mg/kg x 2 days) followed by PBSCT. He responded to this
      therapy and obtained a CR for 10 months. The results suggested the method was
      promising for patients with chemotherapy-resistant and/or poor prognostic
      testicular cancer.

PMID- 7514698
TI  - [Expression of integrin molecule in urological tumor cell lines by using RT-PCR
      method].
AB  - Integrins are heterodimer molecule that are composed of one alpha subunit and one
      beta subunit. Integrins appear to be the major receptors by which cells attach to
      extracellular matrices, and some integrins also mediate important cell-cell
      adhesion event. In recent years signaling pathway via beta subunit of integrin
      molecule has been clarified, and 8 kinds of integrin beta subunit are known to
      exist. And so we investigated the expression of integrin beta subunit in various
      urological tumor cell lines by using RT-PCR method. Materials are composed of 8
      renal cell carcinoma cell lines, 2 urinary bladder carcinoma cell lines, a
      testicular tumor cell line and a prostate tumor cell line. All 12 cell lines
      express integrin beta 1 subunit. The expression rate of beta 4 subunit in renal
      cell carcinoma lines are lower than that in other urological tumor cell lines.
      The expression of beta 6 subunit was observed in renal cell carcinoma cell lines
      and testicular tumor line. In testicular tumor cell line we also found the
      expression of beta 2 subunit which expression had been believed to be specific in
      leukocyte.

PMID- 7514700
TI  - Fluorimetric determination of electrically evoked increase in intracellular
      calcium in cultured cerebellar granule cells.
AB  - A technique is described to measure the electrically evoked increase in
      intracellular calcium in cerebellar granule cells cultured on glass coverslips
      and preloaded with FURA-2. To minimize light scattering, the coverslip containing
      the granules was placed in the fluorimeter cuvette at a 30 degrees angle to the
      exciting light beam. The cuvette was provided with 2 platinum electrodes so as to
      stimulate the neurons with a tangential field. The [Ca2+]i transients were
      maximized by omitting Mg2+. The fluorescence peaks were directly related to the
      pulse (1 ms, 100 mA) frequency and to the train length. The responses were
      completely tetrodotoxin- and [Ca2+]o-dependent and could be replicated 5-6 times
      at 5-min intervals. At the stimulation rate of 20 Hz for 5 s, a condition
      ensuring submaximal peaks, the [Ca2+]i rose from the basal levels of 41 +/- 2.7
      nmol/l to 89.6 +/- 5.8 nmol/l. The participation of various membrane channels in
      the electrically induced [Ca2+]i increase was demonstrated. 4-Aminopyridine (1
      mM) increased the height of the peaks to 240%. Both nifedipine (10 microM) and
      omega-conotoxin (1 microM) reduced the transients by about 25%. The residual
      response (in the absence of Mg2+) depended mostly on the release of endogenous
      glutamate as it proved sensitive to NMDA, AMPA and t-ACPD receptor antagonists.
      Since a technique to measure the electrically evoked release of D-[3H]aspartate
      is presently available, the parallel determination of release and of [Ca2+]i in
      twin populations of cultured granule cells is possible.

PMID- 7514701
TI  - Multiple anterograde tracing, combining Phaseolus vulgaris leucoagglutinin with
      rhodamine- and biotin-conjugated dextran amine.
AB  - The simultaneous use of different neuroanatomical anterograde tracers provides a
      potentially powerful method to study the convergence of afferent systems in a
      particular brain area. However, a simple routine procedure to apply multiple
      anterograde tracers in conjunction with their simultaneous visualization is still
      missing. We report an easy and straightforward application of three sensitive
      anterograde tracers: Phaseolus vulgaris leucoagglutinin (PHA-L), rhodamine
      conjugated dextran amine (RDA) and biotin-conjugated dextran amine (BDA). These
      tracers can be visualized simultaneously and permanently through a triple
      staining procedure with nickel-enhanced diaminobenzidine (DAB-Ni), DAB and 1
      naphthol/Azur B as chromogens. Our test model comprised the projections from the
      nucleus reuniens thalami and entorhinal cortex. Both projection systems show a
      high degree of overlap in their terminal fields in the hippocampus. Two tracers
      were injected in the left and right entorhinal cortex, respectively; a third
      tracer was injected in the nucleus reuniens. This combination of injections
      provided a good opportunity to compare the three tracers in one and the same
      animal. PHA-L, RDA and BDA, injected in either of the injection sites, turned out
      to be equally sensitive and revealed the morphology of the involved projection
      systems in great detail. The triple-staining protocol yielded an excellent,
      simultaneous detectability of the three tracers with a remarkably low background
      level. Thus, the combination of the anterograde tracers PHA-L, RDA and BDA, in
      conjunction with the triple-staining procedure, offers a very attractive approach
      for neuroanatomical research.

PMID- 7514699
TI  - [Low dose COMPE. Cisplatin, vincristine, methotrexate, peplomycin, etoposide
      chemotherapy for advanced testicular cancer].
AB  - We presented 15 patients with advanced testicular cancer treated with to 7
      courses (mean: 3.2 courses) of COMPE chemotherapy. The low dose COMPE, given 14
      patients, consisted of the chemotherapeutic agents as follows: cisplatin, 5 mg/m2
      by intravenous push infusion and thereafter 25 mg/m2 by continuous 24-hour
      infusion on day 3 and 30 mg/m2 by continuous 24-hour-infusion on day 4;
      vincristine, 0.6 mg/m2 by drip intravenous infusion (div) on days 1 and 2;
      methotrexate, 10 mg/m2 by div on day 1; peplomycin, 10 mg/m2/day, divided to
      three times by intramuscular injection on days 1 to 3; etoposide, 100 mg/m2, by
      div on days 3 to 5. The regular dose COMPE (given one patient) had CDDP dosage up
      to 50 mg/m2/day on days 3 and 4. the regimens were given every 3 or 4 weeks in
      admission. Patients were adequately hydrated but no diuretics were used. The
      patients were diagnosed as 5 seminomas with 4IIA and one IIB and as 10 non
      seminomas with 2IIA, one IIB, one IIIB 1,4 IIIB2, and 2 IIIC stagings,
      respectively. Of the 15 patients, 12 patients are alive with no evidence of
      disease at 13-86 months (mean: 39.5 months) of follow-up duration. Six patients
      achieved complete remission. Of 8 patients achieved partial remission with
      chemotherapy alone, 6 patients achieved complete remission by following resection
      of residual masses or irradiation but another 2 patients (IIB2:1, IIIC:1) failed
      to achieve complete remission had relapse and died after 19 and 25 months,
      respectively. One patient (IIIC) showed no change had progression and died after
      5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514703
TI  - [Comparison of two commercial techniques for the identification of hepatitis C
      virus antibodies, RIBA and MATRIX].

PMID- 7514702
TI  - Orthotopic liver transplantation for preoperative early-stage hepatocellular
      carcinoma.
AB  - OBJECTIVE: To report our experience with orthotopic liver transplantation (OLT)
      for highly selected patients with early-stage hepatocellular carcinoma (HCC).
      DESIGN: We retrospectively analyzed the demographic, clinical, pathologic, and
      survival data on 21 patients with HCC who underwent OLT at the Mayo Clinic
      between 1985 and 1993. MATERIAL AND METHODS: The 21 patients were categorized
      into three groups: (1) those with incidental HCC (no evidence of HCC
      preoperatively), (2) those with a unicentric hepatic lesion without vascular
      invasion, and (3) those with an increased serum alpha-fetoprotein (AFP)
      concentration but no detectable mass lesion in the liver. RESULTS: For the seven
      patients with incidental HCC, the 2-year disease-free survival was 68.5%. For the
      eight patients with a mass lesion, the 2-year disease-free survival was only 50%.
      Operative staging revealed more advanced stage disease than had been found on
      preoperative assessment in five of these eight patients. For the six patients
      with an increased serum AFP value but no mass lesion, the 2-year disease-free
      survival was 80%. Tumor recurrence was the major cause of all deaths in this
      series. CONCLUSION: Disease-free survival for patients with radiographic early
      stage HCC was suboptimal because of understaging of the disease preoperatively.
      In contrast, our initial experience with OLT for patients with an increased serum
      AFP value in the absence of a mass lesion in the liver was favorable.

PMID- 7514704
TI  - [Travel abroad: gammaglobulin or a vaccine against hepatitis A?].

PMID- 7514705
TI  - Effects of odorants and irritants on respiratory behavior.
AB  - A technique that combines psychophysical measurements with continuous recording
      of nasal patency and respiratory behavior was used to study the psychophysical
      and respiratory responses of 10 subjects to well-controlled stimulation with
      three compounds differing in relative stimulatory effectiveness for nasal
      olfactory and trigeminal chemoreceptors. All four concentrations of acetic acid,
      amyl acetate, and phenethyl alcohol were well above the odor detection threshold.
      The magnitudes of both the increase in odor strength and nasal irritation and the
      decreases in tidal volume were greatest for acetic acid and least for phenethyl
      alcohol. Among the odorants, differences in nasal irritation were greater than
      those in odor strength, and tidal volume appeared to have a reasonably close and
      inverse relationship to nasal irritation.

PMID- 7514708
TI  - Potentiation of antigen-induced histamine release from rat peritoneal mast cells
      through a direct interaction between mast cells and non-mast cells.
AB  - Rat peritoneal mast cells, which had been sensitized two days earlier by an
      intraperitoneal injection of rat monoclonal IgE antibodies, were purified by
      density gradient centrifugation with 60% Percoll (cell purity > 95%). Histamine
      release from the purified mast cells (PMC) was then compared to that of a non
      purified preparation (peritoneal exudate cells; PEC). Both PEC and PMC released
      similar amounts of histamine upon stimulation with calcium ionophore A23187 and
      compound 48/80. In contrast, antigen-induced histamine release from PMC was very
      low compared to that of PEC. PEC released up to 30% of total histamine upon
      challenge with 1 microgram/ml of antigen, whereas histamine release from PMC was
      only one third or less than that of PEC. When PEC was suspended in 60% Percoll
      and treated for a period needed for purification, the reduction of antigen
      induced histamine release was negligible. Mast cells purified by centrifugation
      on a metrizamide gradient released only small amount of histamine similar to
      Percoll-purified mast cells. Non-mast cells (NMC) recovered from the interface of
      the 60% Percoll potentiated the antigen-induced histamine release from PMC
      concentration- and time-dependently. The supernatant of the NMC suspension which
      was incubated at 37 degrees C for 60 min, however, failed to potentiate histamine
      release in PMC. We concluded therefore that separation media such as Percoll and
      metrizamide do not cause the low antigen-induced histamine release in PMC, but
      that the separation of mast cells from other cells present in the peritoneal
      cavity itself causes it. Antigen-induced mast cell histamine release is
      potentiated through a direct interaction between mast cells and NMC, and some
      cell surface molecules also seem to be involved.

PMID- 7514707
TI  - In vivo evidence for the activation of a septide-sensitive tachykinin receptor in
      guinea pig bronchoconstriction.
AB  - Intravenous administration of the undecapeptide [Sar9]substance P (SP) sulfone
      (1.5 nmol/kg) and the hexapeptide [Glp6,Pro9]SP(6-11) (septide; 0.4 nmol/kg)
      produced a comparable (about 30-40% of maximal effect) increase of insufflation
      pressure (bronchospasm) in anesthetized guinea-pigs. The non peptide NK-1
      receptor antagonist, (+/-)CP 96,345 and the peptide NK-1 receptor antagonist, GR
      82,334 antagonized dose-dependently the response to both agonists. Both
      antagonists were more potent against septide than against [Sar9]SP sulfone (9 and
      4 fold difference in ED50 for (+/-)CP 96,345 and GR 82,334, respectively). These
      findings indicate that a 'septide-sensitive' mechanism mediates
      bronchoconstriction in vivo and it influences the estimate of the potency of NK-1
      receptor antagonists.

PMID- 7514709
TI  - A vascular smooth muscles nitric oxide relaxation by a mechanism distinct of
      calcium changes.
AB  - Prostaglandin F2 alpha contracts coronary arteries smooth muscles under
      conditions of extra cellular and intracellular calcium depletion. In these
      conditions, nitrogen-oxide-containing vasodilators or natural EDRF(s) released by
      the kinins, substance P and bradykinin, from the endothelium relax strips of pig
      coronary arteries. This indicates that nitric oxide not only needs to lower
      cytosolic free calcium to relaxes the smooth muscles, but in addition another
      mechanism, independent of cytosolic calcium changes, is necessary to fully relax
      strips contracted by Prostaglandin F2 alpha.

PMID- 7514706
TI  - Role of detoxication pathways in acute toxicity levels of phosphorothionate
      insecticides in the rat.
AB  - Phosphorothionate insecticides and their active oxon metabolites can be
      detoxified by a variety of hepatic mechanisms. Cytochrome P450-mediated
      dearylation activity was higher in males than in females. While dearylation was
      induced by phenobarbital in both sexes, it was induced by beta-naphthoflavone in
      females only. Detoxication of oxons in the presence of EDTA was inducible by
      phenobarbital, was higher in males than in females, and paralleled aliesterase
      activity. In vitro Ca(++)-dependent A-esterase-mediated hydrolysis of
      chlorpyrifos-oxon but not of paraoxon occurred at biologically relevant nM
      concentrations. This hydrolysis was also inducible by phenobarbital. Glutathione
      mediated conjugation did not appear to be relevant to the disposition of the
      phosphorothionates studied here. Hepatic detoxication via dearylation,
      aliesterase phosphorylation and A-esterase-mediated hydrolysis (for some
      organophosphates) all appear to be relevant reactions in the attenuation of acute
      toxicity.

PMID- 7514710
TI  - Constitutive mu opioid receptor activation as a regulatory mechanism underlying
      narcotic tolerance and dependence.
AB  - Chronic administration of narcotic mu opioid agonists results in tolerance and
      dependence. We propose that agonist stimulation causes a gradual conversion of mu
      receptors to a constitutively active state (mu*) as a key step in tolerance and
      physical dependence. We provide evidence in support of the existence of mu* in
      human neuroblastoma cells, SH-SY5Y, and mu* upregulation during morphine
      treatment. Naloxone blocked mu* activity, acting as an antagonist with negative
      intrinsic activity which accounts for its high potency in eliciting withdrawal.
      In contrast, the mu selective antagonist CTAP did not affect mu* activity but
      inhibited naloxone's effect. The protein kinase inhibitor H7 was found to
      suppress mu* formation, suggesting that mu* is phosphorylated. In a model of
      acute morphine tolerance/dependence in mice, H7 prevented naloxone induced
      withdrawal jumping and reversed morphine (antinociceptive) tolerance. CTAP caused
      only mild withdrawal and attenuated naloxone induced withdrawal, as predicted for
      an antagonist without negative activity. These results support a role for
      constitutive mu receptor activation in narcotic tolerance and dependence,
      affording potential separation of acute and chronic narcotic effects.

PMID- 7514711
TI  - [G-proteins, receptor signal transduction, and growth hormone secretion].

PMID- 7514714
TI  - Effects of tyrphostins on the activated c-src protein in NIH/3T3 cells.
AB  - Tyrphostins are synthetic compounds that have been described as in vitro and in
      vivo inhibitors of epidermal growth factor receptor tyrosine kinase activity. In
      NIH/3T3 cells transfected with the c-src/F527 gene, an increase in the level of
      tyrosine phosphorylation of several proteins, including pp125FAK, within a group
      of proteins of 120 kDa, of p85 (cortactin), and of p62 is observed, which is due
      to the elevated kinase activity of the resulting encoded pp60F527 protein. In the
      transfected cells, we showed that the tyrphostins we used, i.e., AG18, AG34, and
      AG82, strongly diminished the tyrosine phosphorylation of these proteins.
      Analysis of the steady state level of pp60F527 in tyr-phostin-treated cells
      revealed that AG34 and AG82, the two most potent compounds, also induced 30 and
      48% decreases, respectively, in the amount of pp60F527, while having no action on
      the levels of other proteins, especially the pp60F527 kinase substrates.
      Measurement of the rates of pp60F527 synthesis and degradation showed that this
      decreased level was due to a slower rate of synthesis in the presence of AG34 and
      AG82. Tyrphostins also reversed the pp60F527-induced transformed morphology of
      NIH/3T3 cells and also inhibited the pp60F527 kinase activity in vitro. We
      conclude that the effects elicited by the tyrphostins occurred not only through
      the inhibition of the pp60F527 protein kinase activity but also through a
      selective reduction of the Src protein steady state level in the cases of AG34
      and AG82. This is a novel mode of action for these two tyrphostins, which were
      the most active compounds in this system.

PMID- 7514712
TI  - Differential RNA editing in closely related introns in Oenothera mitochondria.
AB  - Introns a/b of the nad2 gene and b/c of the nad1 gene in Oenothera mitochondria
      were found to be closely related. Within a scaffold of conserved sequence
      regions, a 48 bp sequence element covering intron domain V and flanking
      nucleotides is identical in both group II introns. The third nucleotide of this
      element is edited in the nad2, but not in the nad1 intervening sequence. The C to
      U editing event compensates an nad2-specific nucleotide mismatch in the stem
      domain IV and thus improves secondary structure stability. This differential
      editing event indicates that the identical upstream 2 and downstream 45
      nucleotides are not sufficient to specify this editing site. Comparison of
      adjacent exon editing patterns in spliced and unspliced transcripts shows a
      higher degree of editing in processed sequences, confirming that RNA editing is a
      posttranscriptional process in plant mitochondria.

PMID- 7514713
TI  - Reinforcement effect of histamine on the differentiation of murine myeloblasts
      and promyelocytes: externalization of granulocyte colony-stimulating factor
      receptors induced by histamine.
AB  - Histamine and recombinant granulocyte colony-stimulating factor (rG-CSF)
      stimulated the differentiation of murine myeloblasts and promyelocytes to mature
      neutrophils. In connection with this, myeloperoxidase activity of these
      progenitor cells was decreased by either histamine or rG-CSF treatment. After
      pretreatment with histamine at 1 microM, both differentiation and the decrease in
      myeloperoxidase activity of myeloblasts and promyelocytes induced by rG-CSF were
      significantly augmented. Binding assays using 125I-labeled rG-CSF showed that the
      number of rG-CSF binding sites on the surface of neutrophil progenitor cells
      increased after histamine treatment. The histamine-induced increase in rG-CSF
      binding appeared to be definitely through H2 receptors. Furthermore, the increase
      in rG-CSF binding sites due to histamine treatment seemed to take place in
      association with the externalization of G-CSF receptors, because 1) the binding
      increase was observed in the presence of cycloheximide, 2) no concomitant
      increase in [3H]leucine uptake was elicited, and 3) colchicine and cytochalasin D
      effectively prevented the increase in rG-CSF binding due to histamine. In
      neutrophil progenitors, cAMP contents increased very rapidly and significantly
      after either histamine or rG-CSF treatment. Moreover, dibutyryl-cAMP increased rG
      CSF binding to neutrophil progenitor cells in a dose-dependent fashion. However,
      when progenitor cells were pretreated with protein kinase A inhibitors, the
      histamine-induced increase in rG-CSF binding was remarkably decreased. This
      result seems to indicate that the stimulatory effects of histamine on rG-CSF
      binding to progenitor cells are intimately related to the cAMP-protein kinase A
      system in neutrophil progenitors. Moreover, c-myc mRNA expression in neutrophil
      progenitors was markedly reduced by either histamine or rG-CSF treatment. It was
      concluded that rG-CSF-induced differentiation of murine neutrophil progenitors
      was augmented by histamine pretreatment mainly due to an increase in rG-CSF
      receptors on these cells and this increase might be related to the
      externalization of rG-CSF receptors.

PMID- 7514715
TI  - Differential changes in cell morphology, macromolecular composition and membrane
      protein profiles of neurons and astrocytes in chronic ethanol treated rats.
AB  - Cellular morphology, macromolecular composition, (DNA, RNA and Protein content)
      marker enzyme activities for neurons [neuron specific enolase (NSE)] and
      astrocytes [glutamine synthetase (GS)] and plasma membrane protein profiles in
      the bulk isolated neurons and astrocytes from control and ethanol treated rats
      were studied. One month aged Wistar rats were given ethanol as sole drinking
      fluid for 10 weeks. Scanning electron microscopy revealed a characteristic cell
      surface smoothening in astrocytes due to ethanol treatment. DNA levels were
      unaltered, while RNA and Protein contents were decreased in astrocytes and
      neurons. Further, 3H-leucine incorporation into proteins was decreased in neurons
      and astrocytes derived from ethanol treated rats indicating reduced protein
      synthesis in neurons and astrocytes. GS activity was affected severely suggesting
      impairment in astrocytic functions. Plasma membrane protein composition was
      analyzed by 2-D electrophoresis. The analysis indicated several protein defects
      in the plasma membranes of neurons and astrocytes, which might be involved in
      'membrane disorder' during ethanol challenge. 125I-Wheat Germ agglutinin binding
      studies showed three prominent proteins (160, 116 and 97 kDa) in astrocyte
      membrane fraction suggesting the possible involvement of N-terminal glycoproteins
      in altered astrocyte morphology during ethanol ingestion. Impairment in the
      astrocyte cell functions, protein changes in plasma membrane and cellular
      morphology studies suggest that astrocytes may be more vulnerable than neurons
      for ethanol effects.

PMID- 7514717
TI  - Transgenic mice: a decade of progress in technology and research.
AB  - In little more than a decade, the techniques developed for altering the genetic
      makeup of laboratory and livestock animals and plants have changed the landscape
      of biological research. It is now possible to introduce virtually any cloned gene
      into the germ line and study the expression pattern and effects of the introduced
      gene, or transgene. This has allowed the extension of in vitro and in vivo cell
      culture studies into whole animal systems in which the introduced gene is subject
      to all normal regulatory processes from the onset of development. Although there
      have been reports of foreign gene expression resulting from direct injection of
      DNA in animals (e.g., Wolff et al., 1990; Zhu et al., 1993), transgenic animals
      are the primary model system for examining molecular genetic phenomena in vivo.

PMID- 7514716
TI  - Human RNaseP RNA and nucleolar 7-2 RNA share conserved 'To' antigen-binding
      domains.
AB  - RNase P in both prokaryotes and eukaryotes is a ribonucleoprotein that cleaves
      tRNA precursors to generate the 5' termini of the mature tRNAs. Many patients
      with autoimmune diseases produce antibodies against a 40 kDa protein (designated
      To or Th antigen) which is an integral component of eukaryotic RNaseP as well as
      nucleolar 7-2 RNP which is identical to the mitochondrial RNA processing (MRP)
      RNP. Interestingly, the To antigen found in human cells and the C5 protein, the
      only protein component of E. coli RNaseP, are antigenically related. In this
      study, we show that a 56 nucleotide-long sequence, corresponding to nucleotides
      20-75 near the 5' end of human RNaseP RNA, is sufficient to bind the To antigen.
      We previously showed that the human To antigen binds to a short distinct
      structural domain near the 5' end of human 7-2/MRP RNA. There is no obvious
      primary sequence homology between the To antigen binding sites in RNaseP RNA and
      7-2/MRP RNA; however, these sequences are capable of assuming a similar secondary
      structure which corresponds to the recently proposed 'cage' structure for RNaseP
      RNAs and 7-2/MRP RNA (Forster and Altman (1989) Cell 62: 407-409). These data are
      supportive of the idea that these two RNAs may have evolved from a common
      progenitor molecule.

PMID- 7514718
TI  - Genomic imprinting: lessons from mouse transgenes.
AB  - Genomic imprinting is a non-Mendelian form of inheritance that results in an
      expression difference between the two parental alleles of an autosomal locus. The
      study of mouse transgenes has provided us with descriptions of a variety of
      imprinting or parent-of-origin effects, thereby anticipating similar inheritance
      phenomena in non-transgenic mice. Many mouse transgenes exhibit parent-of-origin
      behavior only on mixed strain backgrounds, whereas others are imprinted on inbred
      strain backgrounds. In the former cases, the parent-of-origin effects are due to
      strain-specific modifiers of DNA methylation and expression. These are inherited
      in a parent-specific fashion and exert their effects after fertilization. In the
      latter cases, true germline transgene imprinting, the creation of an imprinted
      locus occurs in a series of sequential steps. First, there is an erasure of the
      imprint from the previous generation in both male and female fetal germ cells.
      Second, upon completion of gametogenesis, distinctive methylation patterns have
      been placed on the transgene sequences of the two mature gametes. Third, only one
      of these inherited patterns is maintained in the early, pre-implantation embryo.
      The pattern of the other parental allele is erased. Finally, the methylation
      pattern of the alleles evolve in the later stages of development, but nonetheless
      the methylation difference (imprint) of the locus persists. Transgene imprinting
      behaviors, either on mixed strain backgrounds and on inbred genetic backgrounds,
      have counterparts in endogenous genetic phenomena.

PMID- 7514719
TI  - LacZ transgenic mouse models: their application in genetic toxicology.
AB  - Gene mutations have been implicated in the etiology of cancer, developmental
      anomalies, genetic disease and aging. Many different methods for mutation
      detection have been developed and applied to obtain a more fundamental insight in
      the chain of molecular events that ultimately lead to mutations. Most of these
      methods, however, can only be applied to cultured cells and therefore do not
      allow comparative analysis of mutations in various organs and tissues in an
      intact organism. The main difficulty in studying mutagenesis in chromosomal DNA
      is to identify and isolate mutated genes with a high efficiency. Here we describe
      the development and application of LacZ transgenic mouse models for studying, in
      different organs and tissues, spontaneous or induced mutations. Such models allow
      study of the induction of DNA damage, repair, mutagenesis and carcinogenesis in
      one animal system. Accordingly, results obtained may ultimately provide greater
      insight into the chain of events from in vivo exposure to genotoxic agents to
      mutations and their ultimate physiological endpoints. In addition to their use in
      fundamental research, transgenic animal mutation models find a major application
      in the field of genetic toxicology testing, in particular with respect to organ
      specificity.

PMID- 7514720
TI  - The use of shuttle vectors for mutation analysis in transgenic mice and rats.
AB  - The establishment in recent years of transgenic shuttle vector-based mutagenicity
      assays has provided improved systems for analysis of mutagenic and carcinogenic
      processes. Results in the mouse have stimulated the development of an alternate
      species suitable for mutation analysis and have increased our understanding of
      the existing models. A previously described shuttle vector (lambda LIZ), based on
      a lacI target gene, was constructed in this laboratory for the study of
      mutagenesis in transgenic mice and in cultured cell lines. The shuttle vector
      allows for several options in its recovery from the host genome and in mutant
      identification. Of the 9 transgenic lineages that were generated with the lambda
      LIZ vector, one was chosen for use in a standardized mutagenicity assay (Big
      Blue, mouse lineage A1). Characterization of this lineage included copy-number
      determination, chromosomal localization of transgene integration and analysis of
      copy-number stability. As part of the validation process, the standardized color
      screening assay has been tested in the mouse, both for spontaneous mutant
      frequencies and with a variety of model mutagenic compounds, and has been shown
      to identify most major classes of mutations as evidenced by mutant spectra data.
      A discussion of the relative sensitivity of the shuttle vector to each of these
      classes of mutations is included. These studies have now been extended to the
      generation of transgenic rats containing the same shuttle vector for cross
      species analysis. Spontaneous mutant frequencies in two transgenic rat lineages
      were measured in liver and in germ cells. Preliminary data suggest that
      spontaneous mutant frequencies in somatic tissue are lower in rats than in mice,
      a result consistent with historical observations of DNA damage and repair in
      these two species. Also under evaluation are alternative selectable systems for
      mutant identification, and hybrid animals obtained from mating lambda LIZ
      transgenics with genetically engineered mice possessing an inactivated tumor
      suppressor gene. It is expected that each of these widely varying endeavors will
      contribute, not only in furthering our understanding of the role transgenic
      systems should play in human risk assessment, but in illuminating the mechanisms
      of mutation in general.

PMID- 7514721
TI  - Radiation-induced point mutations, deletions and micronuclei in lacI transgenic
      mice.
AB  - Ionizing radiation induces gene mutations (point mutations, deletions and
      insertions) as well as chromosome damage in mammalian cells. Although these
      effects have been studied extensively in cells in culture, until recently it has
      not been possible to analyze the mutagenic potential of ionizing radiation in
      vivo, especially at the molecular level. The development of transgenic
      mutagenesis systems has now made it possible to study the effects of ionizing
      radiation at both the molecular and chromosomal levels in the same animal. In
      this report we present preliminary data on the response of Big Blue lacI
      transgenic mice to ionizing radiation as measured by lacI mutations and
      micronuclei. C57Bl/6 transgenic mice were irradiated with 137Cs gamma-rays at
      doses ranging from 0.1 to 14 Gy, and expression times ranging from 2 to 14 days.
      Dose-related increases in the mutant frequency were observed after irradiations
      with longer expression times. Mutant plaques were analyzed by restriction enzyme
      digestion to detect large structural changes in the target sequence. Of 34 gamma
      ray-induced mutations analyzed, 4 were large-scale rearrangements. 3 of these
      rearrangements were deletions within the lacI gene characterized by the presence
      of short regions of homology at the breakpoint junctions. The fourth
      rearrangement was a deletion that extended from within the alpha lacZ gene into
      downstream sequences and that had 43 bp of homology at the junction. These data
      indicate that the Big Blue lacI transgenic mouse system in sensitive to the types
      of mutations induced by ionizing radiation. To determine whether the presence of
      the transgene affects micronucleus induction we compared the response of
      nontransgenic to hemizygous transgenic B6C3F1 mice and the response of
      nontransgenic to hemizygous and homozygous transgenic C57Bl/6 mice. The presence
      or absence of the lacI transgene had no effect on spontaneous micronucleus
      frequencies for either strain. However, radiation-induced micronucleus
      frequencies were significantly higher in hemizygous lacI B6C3F1 mice than in
      nontransgenic litter mates; the converse was true in C57Bl/6 mice. These data
      suggest that the lacI transgene does not cause chromosome instability as measured
      by spontaneous micronucleus levels. However, the response of these transgenic
      mice to a variety of clastogenic agents needs to be investigated before they are
      integrated into standard in vivo assays for chromosome damage.

PMID- 7514722
TI  - Initial experiences and future directions for transgenic mouse mutation assays.
AB  - Transgenic mice have introduced new possibilities in the field of mutation
      research and safety testing. Using lacZ transgenic mice (Muta Mouse), we have
      combined the peripheral blood micronucleus assay with the transgenic mouse
      mutation assay, enabling the concomitant detection of gene mutations and
      micronucleus induction in vivo in the same animals (Suzuki et al., 1993). Several
      mutagens, i.e., mitomycin C (MMC), ethyl nitrosourea (ENU), ethyl
      methanesulfonate (EMS) and diethyl nitrosamine (DEN), were tested in this
      combined assay. All of them increased the lacZ mutant frequency in bone marrow or
      liver, and all except DEN induced micronuclei in peripheral blood. These initial
      studies demonstrated that genotoxicity in vivo could be detected with these two
      endpoints and, more importantly, that some specificity exists among these tissues
      analyzed. Although transgenic mouse mutation assays have many potential
      applications in in vivo mutation research, several problems stand in the way of
      wider use. Paramount among these are cost and labor intensiveness. The color
      screening systems for lacZ or lacI mutation detection require large numbers of
      plates and tedious scoring processes. In order to make significant advances in
      this field, it will be necessary to use positive selection for induced mutants,
      such as has been described recently for the lacZ and lacI transgenic mouse
      models.

PMID- 7514723
TI  - Tissue-specific induction of mutations by streptozotocin in vivo.
AB  - Streptozotocin has been reported to induce DNA damage in mouse liver although
      malignant tumors were not induced in this organ. DNA damage had not yet been
      monitored in the mouse kidney which was the tumor target organ in two mouse
      studies. In order to elucidate target organ specificity of genotoxicity and of
      tumorigenesis, we investigated the induction of DNA damage (microgel
      electrophoresis assay) and mutations (LacI transgenic mouse mutation assay) in
      the liver and kidney of male C57BL/6 mice. Our results show that the microgel
      electrophoresis assay was more sensitive and revealed the genotoxic potential of
      streptozotocin at lower doses than the mutation assay. It was, however, less
      specific in that DNA damage was induced both in target and non-target tissues of
      carcinogenesis at a similar potency. In contrast, the mutation analysis revealed
      the kidney to be more sensitive when the induced mutation frequencies are
      expressed as a multiple of the respective spontaneous rates. We conclude,
      therefore, that the carcinogenic organotropy of streptozotocin correlates better
      with its tissue-specific mutagenicity than with its pattern of inducing DNA
      damage when the two in vivo genotoxicity assays mentioned above are used. A
      combined use of the microgel electrophoresis assay and the transgenic mouse
      mutation assay is proposed for investigations of tissue-specific genotoxicity.

PMID- 7514725
TI  - A consideration of the advantages and potential difficulties of the use of
      transgenic mice for the study of germinal mutations.
AB  - The utility of transgenic mouse systems in the study of germ-cell mutations is
      discussed. These systems promise to fill a gap in the evaluation of potential
      genotoxic agents between the identification of mutagens in short-term test
      systems and evaluation of human genetic risk. A less appreciated major
      contribution that transgenic systems can make is as research tools for achieving
      an understanding of the mechanisms of mutation induction in germ cells. Questions
      concerning the germ-cell mutations using transgenic systems include whether these
      systems can detect large genetic lesions, whether they can detect mutations in
      repair-deficient male germ-cell stages, whether it is valid to extrapolate
      mutational spectra from transgenes to endogenous genes, and whether the
      transgenic systems can be used to address issues concerning differences in locus
      sensitivities to mutation. Available shuttle-vector systems are not suitable for
      the direct detection of mutations in female germ cells. Future directions for
      development include the use of the present systems in research and testing and
      the development of systems with new capabilities.

PMID- 7514727
TI  - Development of a lambda-based complementation assay for the preliminary
      localization of lacI mutants from the Big Blue mouse: implications for a DNA
      sequencing strategy.
AB  - The Big Blue transgenic mouse carrying the E. coli lacI gene as a mutational
      target in a lambda-based shuttle vector has been receiving increasing attention
      in genotoxicity testing because it offers the potential of studying mutation in a
      mammalian system in vivo. The system not only provides information on mutant
      frequency, but it also offers the potential of providing information about
      mutational specificity. Such data is not only important for studies of mutational
      mechanisms; it offers a critical advantage for determining the mutational
      response at levels where significant increases in mutant frequency have not been
      discerned. The repeated sequencing of the entire 1080-bp lacI target, however,
      remains a formidable task. Here we report on the adaptation of the "negative
      complementation" assay for the lacI-d phenotype to accommodate the lambda lacI
      recovered from the Big Blue transgenic animal. This assay permits the
      localization of mutations to an approximately 330-bp region to facilitate the
      production of mutational specificity data. The assay is based upon lysogenization
      of the lambda containing the lacI mutation into a lacI+ host. Of 107 sequenced
      lacI mutants recovered from Big Blue mice, 74 were identified as NC+ (lacI-d)
      using this assay. Of these 74, 49 occurred in the region 32-208 bp, which has
      traditionally been viewed as the NC+ domain. 33 of these mutations were
      previously identified as producing the NC+ phenotype while another 7 occurred at
      sites where NC+ mutants have been recovered, but involved a new base
      substitution. 9 mutants involved new sites. An additional 25 mutants located
      downstream of the presumed NC+ region were also found to be NC+ as determined by
      their blue colour on X-gal plates. Of these, 18 occurred in the 209-360-bp
      region. In parallel, 54 lacI mutants carrying unknown mutations were examined. 37
      of these produced blue colonies in this assay. The sequencing of these mutants
      revealed that 20 (54%) of the 37 mutants were located in the 32-208-bp region.
      This complementation assay can potentially reduce the amount of DNA sequencing
      necessary to produce a mutational spectrum by optimising the choice of sequencing
      primers, and thus provide a significant saving of the material and time required.
      Furthermore, evidence indicates that the restriction of the mutational target to
      the NC+ region extends these savings without reducing the usefulness of the
      mutational specificity data.

PMID- 7514724
TI  - Mutation studies with dimethyl nitrosamine in young and old lac I transgenic
      mice.
AB  - Young adult (approximately 8 w) and old (approximately 72 w) lac I transgenic
      mice have been exposed to a single oral dose of dimethyl nitrosamine (NDMA). 2.5
      h later unscheduled DNA synthesis was observed in the liver of the young animals
      (19.5 NG; control value -3.4 NG). The frequency of lac I- mutations in the liver
      of the young animals was elevated 7, 10 and 20 days after dosing. A similar fold
      increase in mutant frequency was seen 7 days after dosing the old animals. It is
      concluded that mutability of the genome of old animals is not significantly
      different to that of young animals. Aspects of the minimum Big Blue assay
      protocol are discussed, as are the differing perceptions of the role of the assay
      in carcinogen hazard assessment.

PMID- 7514726
TI  - How precisely can data from transgenic mouse mutation-detection systems be
      extrapolated to humans?: lesions from the human factor IX gene.
AB  - Transgenic mutation-detection systems have been pioneered in mice, but the
      approach is applicable to any species in which transgenic animals can be
      generated. The observed mutations seen in mutation-detection systems are
      influenced by the underlying pattern of mutation, i.e., the mutational pattern
      that occurs in wild-type organisms in endogenous segments of DNA that are not
      under selective pressure. Unfortunately, the biology of most genes and assays
      markedly skew the underlying pattern of mutation. Herein, we raise multiple
      issues that must be addressed in order to estimate the underlying pattern of
      spontaneous mutation from transgenic mouse mutation-detection systems. If these
      issues can be addressed, the underlying pattern of spontaneous mutation can then
      be deduced for multiple cell types and for transgenes integrated into different
      parts of the genome. Even though transgenic methodology cannot be applied
      directly to humans, it is likely that comparable data on the underlying pattern
      of spontaneous mutation will be available in humans. Such data are currently
      available for germline mutations in the factor IX gene. These data are reviewed
      because of their relevance to two of the multiple issues that must be addressed
      in transgenic mouse mutation-detection systems: (1) How can the underlying
      pattern of mutation be deduced from the observed pattern? and (2) How similar are
      the underlying patterns of mutation in humans and in mice? The analysis of recent
      germ-line mutation in the factor IX gene yield estimates of the mutation rates
      per base pair per generation. In brief, the mutation rates vary from 0.037 x 10(
      10) for deletions (> 20 bp) to 360 x 10(-10) for transitions at the dinucleotide
      CpG. If these mutation rates are extrapolated to the entire genome, the aggregate
      mutation rate is estimated to be 36 x 10(-10). This implies that the diploid
      genome of each person contains about 21 de novo mutations. In the future, the
      underlying pattern of spontaneous mutation will be deduced for multiple human
      genes and these will serve as benchmarks to assess the similarity of the
      mutational process in humans and in mice.

PMID- 7514729
TI  - Gene-targeting and the p53 tumor-suppressor gene.
AB  - Gene-targeting techniques are now frequently applied to embryonic stem (ES) cells
      to introduce mutations of endogenous genes in mice. Modifications introduced into
      tumor-suppressor genes by this technology have produced mice and cell lines with
      unique tumorigenic and growth characteristics, respectively. A number of
      strategies have been developed to enhance the efficiency of homologous
      recombination between targeting vectors and endogenous genes. This review
      describes recent advances in the techniques used to construct mice with a variety
      of genetic alterations. In addition, an application of gene-targeting is
      illustrated in the study of a class of genes with tumor-suppressor function.
      Recent findings from experiments using gene targeted mice to study the p53 tumor
      suppressor gene are discussed and the potential of gene-targeting for the
      discovery and study of novel tumor-suppressor genes are explored.

PMID- 7514728
TI  - Alkyltransferase transgenic mice: probes of chemical carcinogenesis.
AB  - Transgenic mice expressing DNA-repair genes are an instructive model with which
      to study the protective role of DNA-repair pathways in both spontaneous and
      chemical carcinogenesis. Of particular interest in chemical carcinogenesis is the
      DNA-repair protein O6-alkylguanine-DNA alkyltransferase (alkyltransferase) which
      repairs O6-alkylguanine-DNA adducts. Transgenic mice carrying expression
      constructs for the alkyltransferase gene--either the human MGMT cDNA or the
      bacterial ada gene--express increased levels of alkyltransferase and have
      increased capacity to remove O6-methylguanine-DNA adducts. Protection from the
      DNA damaging effects of N-nitroso compounds occurs specifically in the cells and
      tissues in which the alkyltransferase transgene is expressed. For instance, mice
      carrying the PEPCKada construct have increased alkyltransferase in the liver and
      more rapid removal of O6methylguanine-DNA adducts. The protective effect is noted
      in hepatocytes, which express PEPCK-linked genes, not in nonparenchymal cells of
      the liver, which do not. Other tissues that express the transgene in the various
      models include the thymus, spleen, testes, muscle, stomach and brain. Mice
      expressing the human alkyltransferase in the thymus have a reduced incidence of
      thymic lymphomas following exposure to methyl nitrosourea (MNU), evidence of a
      role for this DNA-repair protein in protection from carcinogenesis due to N
      nitroso compounds. Protection has also been observed in the induction of hepatic
      tumors by N-nitroso-dimethylamine (NDMA). These models will be used to identify
      whether overexpression of a single DNA-repair gene can block the carcinogenic
      process of N-nitroso compounds in many different tissues.

PMID- 7514732
TI  - Report on the International Workshop on Standardisation of Genotoxicity Test
      Procedures. Melbourne, February 1993.

PMID- 7514733
TI  - International Workshop on Standardisation of Genotoxicity Test Procedures.
      Commentary.

PMID- 7514734
TI  - International Workshop on Standardisation of Genotoxicity Test Procedures.
      Summary of major conclusions.

PMID- 7514731
TI  - A recombination-based transgenic mouse system for genotoxicity testing.
AB  - It is well established that mutagens induce recombination in cultured cells and
      experimental organisms. Presumably, this is a consequence of the DNA-damage
      triggering cellular-repair mechanisms. The relationship between recombination and
      mutagenicity has been exploited in submammalian organisms, such as yeast, to
      assay the ability of chemical agents and radiation to induce a form of
      recombination called gene conversion--the non-reciprocal transfer of genetic
      information. This work has demonstrated the efficacy of predicting mutagenicity
      on the basis of recombination induction. Here, we describe the utilization of a
      transgenic mouse system for efficient detection of germ-line gene-conversion
      events as a mutagen-screening tool. These mice contain two mutually defective
      reporter (lacZ) genes under the regulatory control of a spermatogenesis-specific
      promoter. A particular intrachromosomal gene conversion event must occur for the
      generation of functional lacZ activity. Conversion events are visualized by
      histochemical staining or flow cytometric analysis of transgenic spermatids. The
      highly mutagenic compound chlorambucil induced a several fold percentage-wise
      increase of lacZ-positive spermatids, whereas acrylamide, a weak genotoxin,
      produced no marked increase in converted spermatids. The results indicate that
      recombination-based transgenic mouse models for genotoxin screening present a
      viable option for inexpensive and rapid whole-animal mutagen testing. The
      particular mice we describe may ultimately prove to be a useful tool for
      identifying agents which can cause heritable genetic mutations in humans.

PMID- 7514730
TI  - DNA damage, oncogenesis and the p53 tumour-suppressor gene.
AB  - The p53 tumour-suppressor gene encodes a transcription factor which plays a
      central role in controlling oncogenic development in mouse and humans. Mice which
      over-express mutant p53 transgenes or have a homozygous deletion of the p53 gene
      show a high frequency of spontaneous tumour development. This review will focus
      on recent developments using these transgenic and null mice which suggest that
      p53 is important in maintaining genomic stability, and is a critical component in
      the cellular response to ionizing radiation.

PMID- 7514735
TI  - International Workshop on Standardisation of Genotoxicity Test Procedures. Report
      of the in vitro sub-group.

PMID- 7514736
TI  - Recommendations for the performance of bacterial mutation assays.
AB  - At the International Workshop on the Standardisation of Genotoxicity Test
      Procedures, in Melbourne (27-28 February 1993), the current international
      guidelines for the correct conduct of bacterial mutation assays were considered,
      and the major differences between them were examined. An attempt was made to
      construct a scientifically based, internationally harmonized protocol. The main
      points of agreement were as follows. The consensus opinion was that there are
      currently insufficient data to justify a preference for either the preincubation
      or plate-incorporation methodologies as the initial test. Whichever method is
      used there was consensus agreement that the bacterial test battery should consist
      of S. typhimurium TA1537, TA1535, TA98 and TA100. There was also consensus that
      the 3 strains TA97a, TA97 and TA1537 could be used interchangeably. Although it
      was not possible to achieve a consensus, the majority of the working group
      members agreed that strains for the detection of mutagens acting specifically on
      AT base pairs should be routinely included within the test battery. These strains
      may be S. typhimurium TA102 or E. coli WP2 strains (WP2 pKM101 and WP2 uvrA or
      WP2 uvrA pkM101). With regard to study design it was universally agreed that 5
      doses of test compound should be used in each experiment, and a majority
      agreement was obtained for 3 plates per dose. The use of 2 plates per dose is
      acceptable ONLY if the experiment is repeated. It is recommended that the
      negative controls may consist of solvent control alone provided that historical
      data are available to demonstrate lack of effect of the solvent in question.
      Positive control compounds should be included in all experiments, although the
      nature of these control compounds need not be specified in the guidelines. There
      was consensus agreement that for non-toxic freely soluble test agents, an upper
      limit of 5 mg/plate should be tested (5 microliters per plate for liquids). For
      insoluble or toxic compounds, the recommendations were the same as those for
      other in vitro tests (see appropriate paper). A consensus agreement was reached
      on the need to carry out further tests if equivocal results are obtained in the
      initial test, although it was generally agreed that the design of the repeat
      study should be left flexible. As there are little or no data to support the use
      of an exact repeat assay, a majority of the group recommended that negative
      results in the first test should be further investigated by either conducting a
      modified repeat (e.g. S9 titration) or by conducting the alternative
      methodology.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514737
TI  - Mammalian cell gene mutation assays working group report.
AB  - As part of the International Workshop on Standardization of Genotoxicity Test
      Procedures, in Melbourne, 27-28 February 1993, various international guidelines
      were examined with respect to protocol issues in the area of mammalian cell gene
      mutation assays. The working group on mammalian cell gene mutation assays
      discussed a wide range of protocol issues related to study design; in most cases
      the recommendations are reasonably consistent with existing guidelines. Agreement
      was reached on several issues as follows. The upper limit of concentration for
      testing non-toxic substances should be 10 mM or 5 mg/ml, whichever is lower. For
      testing toxic substances the criteria of an acceptable upper limit of
      concentration should yield 10-20% survival. Any of several established mammalian
      cell mutation assays (L5178Y TK+/-, CHO/HPRT, AS52/XPRT, V79/HPRT) can be used to
      evaluate mutagenesis in mammalian cells; the ouabain (Na/K-ATPase) system is not
      an acceptable mutation assay for routine evaluation of mutagenesis in mammalian
      cells. Ability to recover small colonies must be convincingly demonstrated when
      using the L5178Y TK+/- mouse lymphoma assay. In the mouse lymphoma assay (L5178Y
      TK+/-), colonies in positive controls and at least two (if available)
      representative positive doses of the test compound should be sized if a positive
      response is seen; in the event of a negative response due to the test compound,
      colony sizing of the positive control is necessary to validate the conduct of the
      assay. Testing both in the presence and absence of S9 metabolic activation is
      necessary. It was not possible to come to a firm conclusion about the length of
      treatment. There was a general agreement that extended treatment times (> 2 cell
      cycles) often bear more disadvantages than advantages and should only be used
      with adequate justification. It is not necessary to repeat clear positive or
      clear negative tests when the assay has been adequately performed; this
      recommendation differs significantly from the UK guidelines. If treatment groups
      are not replicated, the numbers of doses tested should be increased; this
      recommendation differs significantly from the UK guidelines. Each laboratory
      should establish a historical database for the performance of a given assay in
      that laboratory.

PMID- 7514738
TI  - Report from working group on in vitro tests for chromosomal aberrations.
AB  - The following summary represents a consensus of the working group except where
      noted. The items discussed are listed in the order in which they appear in the
      OECD guideline (473) for easy reference. Metabolic activation. S9 from animals
      induced either with Aroclor 1254 or with the combination of phenobarbital with
      beta-naphthoflavone is acceptable, and other systems could be used with suitable
      justification. Exposure concentrations. The upper limit of testing should be 10
      mM (or 5 mg/ml where molecular weight is not known or mixtures are being tested),
      whichever is lower. Where this limit is inappropriate the investigator should
      give detailed justification of the choice of top concentration. Cytotoxicity
      should be measured not only in range-finding tests but also concurrently with the
      assay for chromosomal aberrations. Cytotoxicity should be assessed by
      measurements of cell growth such as cell counts or confluence estimation. Mitotic
      index data alone are not a sufficient measure of cytotoxicity, except in the case
      of blood cultures for which other methods are impractical. Cytotoxicity at the
      top dose should be greater than 50% of concurrent negative/solvent controls, if
      this can be achieved without exceeding a concentration limit of 10 mM or 5 mg/ml.
      There should be at least three concentrations scored for aberrations (each with
      and without S9), covering a toxicity range down to a concentration giving little
      or no cytotoxicity. This will usually mean that the concentrations scored will be
      quite closely spaced. It was not possible to reach a consensus on the issue of
      solubility limits. The group did not agree on whether (a) solubility rather than
      cytotoxicity should be the limiting factor, such that only one top dose with
      evident precipitate should be scored even if toxicity is not observed, or (b)
      several concentrations with evident precipitate should be scored for aberrations
      if this were necessary to obtain cytotoxicity. It was agreed that evidence of
      precipitation should be determined in the final culture medium. Controls.
      Concurrent positive controls are required but the working group thought it
      inappropriate to specify the control chemicals or the degree of response that
      should be obtained, leaving it up to the test laboratory to demonstrate that the
      system was working adequately based on historical data within the laboratory. It
      is not necessary to include both negative and solvent controls concurrently with
      the aberration test; solvent controls alone are acceptable provided that the
      laboratory has data to demonstrate that there is no effect of the solvent on
      baseline values. Preparation of cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514740
TI  - International Workshop on Standardisation of Genotoxicity Test Procedures. Report
      of in vivo subgroup.

PMID- 7514739
TI  - Recommendations for the performance of UDS tests in vitro and in vivo.
AB  - The Working Group (WG) dealt with the harmonization of routine methodologies of
      tests for unscheduled DNA synthesis (UDS) both in vitro and in vivo. In contrast
      to the existing guidelines from OECD, EPA and EC on in vitro UDS tests (there is
      no Japanese UDS guideline), the Working Group recommends that in general in vitro
      UDS tests should be performed with primary hepatocytes. For routine applications
      any other cell types would need special justification. Hepatocytes from male rats
      are preferable, unless there are contra-indications on the basis of e.g.
      toxicokinetic data. According to the OECD, EPA and EC guidelines, UDS may be
      analysed by means of autoradiography (AR) or liquid scintillation counting (LSC).
      The WG recommends use of AR. LSC is less suitable due to the problem of
      differentiation between UDS activity and replicative DNA synthesis, and the
      disadvantage that cells cannot be analysed individually. Since a specific cell
      type was recommended by the WG, methodological aspects could be described in more
      detail than in the present guidelines. For in vitro tests, it was agreed that the
      initial viability of freshly isolated hepatocytes should be at least 70%. With
      regard to the need for confirmatory experiments in the event of a clear-cut
      negative result, the majority view was that confirmation by a second (normally
      not identical) experiment is still needed; this is in line with the present OECD
      and EC guidelines. Evaluation of results from UDS tests should be based primarily
      on net nuclear grain (NNG) values, although it is recognised that nuclear and
      cytoplasmic grains result from different biological processes. Since grain counts
      are influenced by a number of methodological parameters, no global threshold NNG
      value can be recommended for discrimination of positive and negative UDS results.
      For in vitro assays, the criteria for positive findings go beyond those of the
      present guidelines and two alternative approaches are given which are based on
      (1) dose-dependent increases in NNG values and (2) reproducibility, dose-effect
      relationship and cytotoxicity. At present there is no official guideline on the
      performance of in vivo UDS tests. Some fundamental recommendations given for in
      vitro methodology also apply to the in vivo assay. For routine testing with the
      in vivo UDS test, again the general use of hepatocytes from male rats is
      recommended. However, concerning the requirement to use one or two sexes,
      consistency with other in vivo genotoxicity assays (e.g. the micronucleus assay)
      would be preferable. As for the in vitro methodology, AR is preferred rather than
      LSC.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514741
TI  - In vivo rodent erythrocyte micronucleus assay.
AB  - The following summary represents a consensus of the working group except where
      noted. The items discussed are listed in the order in which they appear in the
      OECD guideline (474) for easy reference. Introduction, purpose, scope, relevance,
      application and limits of test. The analysis of immature erythrocytes in either
      bone marrow or peripheral blood is equally acceptable for those species in which
      the spleen does not remove micronucleated erythrocytes. In the mouse, mature
      erythrocytes are also an acceptable cell population for micronucleus analysis
      when the exposure duration exceeds 4 weeks. Test substances. Organic solvents
      such as DMSO are not recommended. Freshly prepared solutions or suspensions
      should be used unless stability data demonstrate the acceptability of storage.
      Vegetable oils are acceptable as solvents or vehicles. Suspension of the test
      chemicals is acceptable for p.o. or i.p. administration but not for i.v.
      injection. The use of any unusual solvent should be justified. Selection of
      species. Any commonly used laboratory rodent species is acceptable. There is no
      strain preference. Number and sex. The size of experiment (i.e., number of cells
      per animal, number of animals per group) should be finalized based on statistical
      considerations. Although a consensus was not achieved, operationally it was
      agreed that 2000 cells per animal and four animals per group was a minimum
      requirement. In general, the available database suggests that the use of one
      gender is adequate for screening. However, if there is evidence indicating a
      significant difference in the toxicity between male and female, then both sexes
      should be used. Treatment schedule. No unique treatment schedule can be
      recommended. Results from extended dose regimens are acceptable as long as
      positive. For negative studies, toxicity should be demonstrated or the limit dose
      should be used, and dosing continued until sampling. Dose levels. At least three
      dose levels separated by a factor between 2 and square root of 10 should be used.
      The highest dose tested should be the maximum tolerated dose based on mortality,
      bone marrow cell toxicity, or clinical symptoms of toxicity. The limit dose is 2
      g/kg/day for treatment periods of 14 days or less and 1 g/kg/day for treatment
      periods greater than 14 days. A single dose level (the limit dose) is acceptable
      if there is no evidence of toxicity. Controls. Concurrent solvent (vehicle)
      controls should be included at all sampling times. A pretreatment sample,
      however, may also be acceptable only in the short treatment period peripheral
      blood studies. A concurrent positive control group should be included for each
      experiment.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514744
TI  - Beta-1 integrins in the normal human glomerular capillary wall: an immunoelectron
      microscopy study.
AB  - The localization of the alpha 2, alpha 3 and alpha 6 subunits of the beta 1
      integrin family on different cells of the glomerular capillary wall and on juxta
      capillary mesangium was investigated using an immunoelectron microscopic
      technique on freshly harvested normal human glomeruli. Alpha 2 beta 1, alpha 3
      beta 1 and alpha 6 beta 1 were weakly expressed on both luminal and abluminal
      surfaces of glomerular endothelial cells; alpha 2 beta 1 and alpha 3 beta 1 were
      also found on the mesangium of the juxta-capillary areas. Alpha 3 beta 1 was
      regularly present in great density on the basal and lateral surface of podocyte
      foot processes, confirming alpha 3 beta 1 as the unique beta 1 integrin on
      glomerular epithelial cells. None of these integrins was strictly polarized along
      the glomerular basement membrane, thus suggesting, in agreement with recent
      literature, that these molecules perform other biological functions in addition
      to adhesivity.

PMID- 7514742
TI  - Report from the working group on the in vivo mammalian bone marrow chromosomal
      aberration test.
AB  - The following summary represents a consensus of the working group, except where
      noted. The goal of this working group was to identify the minimal requirements
      needed to conduct a scientifically valid and practical in vivo chromosomal
      aberration assay. For easy reference, the items discussed are listed in the order
      in which they appear in OECD guideline 475. Specific disagreement with the
      current and/or proposed OECD guideline is presented in the text. Introduction,
      purpose, scope, relevance, application, and limits of test: This test would not
      be appropriate in situations where there was sufficient evidence to indicate that
      the test article or reactive metabolites could not reach the bone marrow. Test
      substances: Solid and liquid test substances should be dissolved, if possible, in
      water or isotonic saline. If insoluble in water/saline, the test substance should
      be dissolved or homogeneously suspended in an appropriate vehicle (e.g.,
      vegetable oil). A suspension was not considered suitable for an intravenous
      injection. The use of dimethyl sulfoxide as an organic solvent was not
      recommended. The use of any uncommonly used solvent/vehicle should be justified.
      Freshly prepared solutions or suspensions of the test substance should be
      employed unless stability data demonstrate the acceptability of storage.
      Selection of species: Any commonly used rodent species was deemed acceptable but
      rats or mice were preferred, with no strain preference. Number and sex: A
      consensus could not be reached as to the requirement for both sexes versus one
      sex in this assay. It was suggested that a single sex should be used unless
      pharmacokinetic and/or toxicity data indicated a difference in metabolism and/or
      sensitivity between males and females. The size of the experiment (i.e., number
      of cells per animal, number of animals per treatment group) should be based on
      statistical considerations. Lacking a formal analysis, it was agreed that at
      least 100 metaphase cells should be scored per animal while at least five animals
      of any one sex should be evaluated per treatment group. Recently, a formal
      analysis of the numbers of cells to score per animal and numbers of animals to
      score per treatment group was conducted at a workshop on statistics for in vivo
      mutagenicity tests (Adler et al., 1994). The conclusion of this workshop was
      that, based on a type I error of 0.05 and a power of 80% to detect at least a
      doubling in the control frequency, the minimal number of cells to score per
      animal was 200 and the minimal number of animals to score per sex per treatment
      group was four.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7514746
TI  - Brain tumors complicated by pneumocephalus following cerebrospinal fluid shunting
      -two case reports.
AB  - A 16-year-old male with cerebellar astrocytoma and a 29-year-old male with
      convexity meningioma, both complicated by hydrocephalus, developed pneumocephalus
      following tumor removal and shunt emplacement. Both patients underwent
      ventriculoperitoneal shunt emplacement and total tumor removal, and were
      discharged from hospital in good condition. After 1 year or 10 months,
      respectively, pneumocephalus and porencephalic cysts in the temporal lobes
      developed. Since neuroradiological examination could not locate the bone defects
      in the skull base, the dura mater covering the anterior cranial fossa was
      repaired. Fistulae were observed in the cribriform plate in both patients.
      Postoperatively, one patient showed persistent cerebrospinal fluid rhinorrhea.
      Intratympanic cerebrospinal fluid retention was demonstrated by tympanic puncture
      ipsilateral to a porencephalic cyst. The other patient again developed
      pneumocephalus. Magnetic resonance imaging indicated that the base of the
      porencephalic cyst was in contact with the tegmen tympani. The dura mater
      covering the floor of the middle cranial fossa was repaired in both patients, and
      the symptoms ameliorated. The bone defects in the skull base were apparently
      deeply involved in the development of the porencephalic cysts, indicating that
      such cysts provide useful information for locating cranial bone defects.

PMID- 7514743
TI  - Summary report of the Working Group on Mammalian Germ Cell Tests.
AB  - The two tests considered by the Working Group were the mammalian germ cell
      cytogenetic assay and the rodent dominant lethal test. It was agreed that both
      tests were mainly used for identification of germ cell hazards, however, that the
      commonly applied protocol of the dominant lethal assay often supplied information
      for hazard characterization such as sensitivity of particular developmental
      stages of male germ cells. No particular species or strains were indicated.
      Concurrent solvent controls were regarded as indispensable for both tests. In the
      discussion of the mammalian germ cell cytogenetic assay, harmonization was
      obtained to a large extent with the cytogenetic bone marrow assay regarding the
      number of animals (5), the number of cells analyzed per animal (200), the highest
      exposure dose (MTD) and sampling times (twice within 24 and 48 h after dosing).
      However, it was pointed out that only the single acute exposure was adequate for
      the mammalian germ cell cytogenetic assay. Furthermore, it was stated that only
      structural chromosome aberrations could be analyzed and that it was not
      informative to score polyploidies or aneuploidies. In the discussion of the
      rodent dominant lethal test, it was stated that the assay was generally performed
      with treated males, however, increasing concern about female specific effects
      required that a protocol for female dominant lethal testing should be developed
      and validated. Acute and subacute treatment schedules were considered equally
      acceptable. It was regarded as highly important that the entire male germ cell
      development from meiosis to mature sperm was covered in the test protocol either
      by the appropriate mating schedules after single dosing or by subchronic dosing
      during the respective period. Postimplantation loss, preimplantation loss and
      fertility rate were the main parameters to be assessed in the rodent dominant
      lethal tests. It was agreed that the size of the experiment depended on the
      spontaneous frequency of dead implants, the mating scheme and the statistical
      design of the experiment.

PMID- 7514747
TI  - Temporary neurological deterioration caused by hyperperfusion after extracranial
      intracranial bypass--case report and study of cerebral hemodynamics.
AB  - A 64-year-old female with occlusion of the left internal carotid artery (ICA)
      developed temporary neurological deterioration after superficial temporal artery
      to middle cerebral artery anastomosis. Preoperative single photon emission
      computed tomography (SPECT) showed marked reduction of the cerebral perfusion
      reserve in the left ICA territory. She suddenly developed aphasia 18 hours after
      operation. Follow-up SPECT revealed temporary hyperperfusion in the left temporal
      lobe, strongly suggesting that this unusual complication resulted from bypass
      flow into the brain tissue with chronic severe ischemia and impaired
      autoregulation.

PMID- 7514748
TI  - Paramedian thalamic infarction following blunt head injury--case report.
AB  - A 19-year-old male was admitted following a blow to the face. Computed
      tomographic (CT) scans 1 hour after injury revealed low-density areas in the
      bilateral thalami and midbrain, which were enhanced postcontrast except for the
      core 3 hours later. CT scans 2 days after injury revealed that the size of the
      low-density areas had increased. CT scans and magnetic resonance images 3 weeks
      after injury disclosed only small infarcted lesions in the bilateral thalami, the
      right side of the midbrain, and the left internal capsule. These findings suggest
      that the injury initially caused thrombus on the basilar arterial wall, leading
      to occlusion of the perforators, but almost all affected perforators were
      recanalized. Bilateral thalamic infarction resulting from head injury is unusual,
      as is the transient nature of the infarction in this case.

PMID- 7514745
TI  - Reduction of superoxide dismutase activity correlates with visualization of edema
      by T2-weighted MR imaging in focal ischemic rat brain.
AB  - This study investigated the correlation between in vivo serial T2-weighted
      magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na+), and
      potassium ion (K+) contents measured in vitro using rat brain following right
      middle cerebral artery occlusion in conjunction with bilateral common carotid
      artery (CCA) occlusion. One hour later the left CCA was released. Serial MR
      images showed edema developed from the outer cortex towards the center. The T2
      signal intensity of the injured right cortex increased with time compared to that
      of the contralateral cortex. Increased Na+ and water and decreased K+ contents
      occurred in the injured cortex, indicating that serial T2-weighted MR imaging
      reflects the changes in water content and Na+ and K+ concentrations determined by
      biochemical techniques. GSH-Px activity was little changed. Total SOD in the
      injured cortex decreased 1 hour after ischemia and remained low throughout the
      experiment. In contrast, SOD activity in the noninfarcted left cortex also
      decreased after 1 hour but returned to normal after 2 hours of ischemia. Our
      results suggest that oxygen free radicals are important in developing ischemic
      brain edema and cerebral infarction.

PMID- 7514749
TI  - Acute cervical spinal epidural hematoma with spontaneous resolution--case report.
AB  - A 54-year-old male presented with spontaneous acute epidural hematoma in the
      ventral cervical spine. The neurological deficits gradually improved
      spontaneously before surgery commenced. Serial magnetic resonance imaging
      demonstrated disappearance of the hematoma. He was managed conservatively and was
      discharged without deficits about 1 month after onset. Immediate surgical
      decompression may not be necessary if neuroimaging and clinical examinations
      suggest that spinal epidural hematoma will resolve spontaneously.

PMID- 7514750
TI  - Spontaneous subperiosteal hematoma of the orbit--case report.
AB  - A 62-year-old female was admitted with complaints of sudden proptosis of the left
      eye and severe left orbital pain without history of trauma or previous illness.
      Computed tomography and magnetic resonance imaging demonstrated a biconvex
      extraconal hematoma in the upper part of the left orbit. Surgical exploration of
      the orbit revealed the presence of a subperiosteal hematoma without a causative
      lesion. Such spontaneous subperiosteal hematoma of the orbit is extremely rare,
      but may result from an occult vascular disorder.

PMID- 7514751
TI  - Giant fusiform aneurysm at the horizontal portion of the middle cerebral artery
      in a child--case report.
AB  - A 13-year-old boy with a rare giant fusiform aneurysm at the horizontal portion
      of the middle cerebral artery (M1) presented with progressively severe throbbing
      headache. The aneurysm was reconstructed by tandem application of nine
      fenestrated clips and coating of the remnant of the aneurysm. However, he was
      readmitted 3 months later because of recurrent aneurysms at the proximal and
      distal M1 portions which had been coated. The aneurysms were trapped after
      rupture occurred during a second operation. Aneurysm trapping combined with
      superficial temporal artery-middle cerebral artery bypass surgery may be a better
      method to treat such aneurysms.

PMID- 7514752
TI  - Double bilateral symmetrical aneurysms--case report.
AB  - A 52-year-old female admitted for subarachnoid hemorrhage and preoperative
      angiography revealed bilateral symmetrical middle cerebral artery aneurysms,
      which were successfully clipped. Post-operative angiography revealed bilateral
      symmetrical aneurysms in the distal anterior cerebral arteries, which were not
      identified on the preoperative angiograms, and were also clipped successfully.
      Such multiple aneurysms should not be treated by bilateral approaches in a one
      stage operation.

PMID- 7514753
TI  - Cryptic arteriovenous malformation of the choroid plexus of the fourth ventricle-
      case report.
AB  - A 54-year-old female presented with a cryptic arteriovenous malformation (AVM) of
      the choroid plexus of the fourth ventricle causing intraventricular hemorrhage.
      Computed tomography and magnetic resonance imaging disclosed the lesion near the
      fourth ventricle, but bilateral vertebral angiograms showed no abnormalities. The
      preoperative diagnosis was cavernous angioma. The mass was removed completely,
      and histological examination demonstrated an AVM of the choroid plexus. Vascular
      malformations of the choroid plexus of the fourth ventricle are extremely rare.
      The possibility of this lesion being the cause of primary intraventricular
      hemorrhage of unknown origin should always be considered.

PMID- 7514754
TI  - Human tail associated with lipomeningocele--case report.
AB  - A 3-month-old boy presented with a tail associated with lipomeningocele. Computed
      tomography and magnetic resonance imaging clearly demonstrated the presence of
      spina bifida and lipoma continuous from the tail to the thickened conus
      medullaris. The human tail may be related to spinal dysraphism and requires
      detailed neuroimaging investigation, and possibly microsurgery to prevent the
      tethered cord syndrome.

PMID- 7514756
TI  - Primitive trigeminal artery variant associated with intracranial ruptured
      aneurysm and cerebral arteriovenous malformation--case report.
AB  - A 48-year-old female presented with a unique combination of ruptured aneurysm of
      the right middle cerebral artery (MCA) manifesting as sudden loss of
      consciousness associated with arteriovenous malformation (AVM) in the right
      parietal lobe and left primitive trigeminal artery (PTA) variant. Angiography
      revealed the right MCA aneurysm, AVM fed by the right anterior cerebral artery
      and MCA, and contralateral PTA variant. The PTA variant was an anomalous
      posterior cerebral artery originating from the ipsilateral cavernous internal
      carotid artery. The neck of the aneurysm was successfully clipped and the AVM was
      totally removed.

PMID- 7514757
TI  - Calcified intracranial metastatic tumor mimicking meningioma--case report.
AB  - A 60-year-old female presented with mild cerebellar dysfunction due to a
      calcified tumor attached to the undersurface of the tentorium cerebelli
      demonstrated by cranial computed tomography, and a lung mass on a chest x-ray
      film. The calcified nature and location made preoperative differentiation between
      metastatic brain tumor and meningioma difficult. Operation subsequently revealed
      that the brain tumor was a metastasis from lung adenocarcinoma. Metastatic brain
      tumors can be calcified, and should be considered in the differential diagnosis
      of calcified intracranial lesions.

PMID- 7514755
TI  - Tuberculous hypertrophic pachymeningitis involving the posterior fossa and high
      cervical region--case report.
AB  - A 44-year-old female presented with a rare tuberculous hypertrophic
      pachymeningitis involving the posterior fossa and high cervical region
      manifesting as progressive multiple cranial nerve pareses and myelopathy
      developing over 6 months. Magnetic resonance imaging demonstrated the thickened
      dura mater and associated syrinx. Despite decompressive craniectomy and
      antituberculous treatment, she died of disseminated intravascular coagulation.
      Hypertrophic pachymeningitis is probably best treated by the most extensive
      excision of affected dura mater possible, unless medical treatment can be
      instituted for an identifiable underlying causative disease.

PMID- 7514758
TI  - Analysis of intracerebral hematoma shapes by numerical computer simulation using
      the finite element method.
AB  - The distortion and stress distribution in the brain caused by putaminal
      hemorrhage were estimated by computer stimulation using the finite element method
      (FEM). The two-dimensional model of a single cerebral hemisphere contained
      cortex, white matter, caudate nucleus, lenticular nucleus, thalamus, falx, and
      lateral ventricle. Five types of intracerebral hemorrhage were modeled at
      different locations in the lenticular nucleus. The models generated putaminal
      hematomas of various shapes influenced by the location of the bleeding points.
      Hematomas caused deformation of the brain, collapse of the lateral ventricle, and
      destruction of the internal capsule. The stress distribution revealed various
      patterns influenced by the site of bleeding. The stress in the area of the
      internal capsule corresponded to the extent of destruction of the internal
      capsule. This study suggests that FEM modeling of putaminal hemorrhage can
      provide a useful simulation.

PMID- 7514760
TI  - Accumulation of exogenous 45Ca after middle cerebral artery occlusion in rats.
AB  - The distribution of exogenous 45Ca in the focal ischemia rat model (middle
      cerebral artery occlusion) was studied using 45Ca autoradiography. High 45Ca
      accumulations were observed in the frontal cortex and caudate-putamen
      corresponding with morphological damage shown by HE staining. Regional 45Ca
      concentrations were calculated from the optical density on the 45Ca
      autoradiograms. Rapid uptake of 45Ca in the ischemic brain occurred during the
      first 5 hours, and continued more slowly between 5 and 24 hours after ischemia.
      The area of 45Ca accumulation was also expanded between 5 and 24 hours. An area
      of low 45Ca concentration around the area of high accumulation developed 5 hours
      after ischemia, which presumably accumulated 45Ca between 5 and 24 hours after
      ischemia. The lower concentration of 45Ca in the periphery of ischemia may result
      from: 1) a decrease in the total amount of calcium due to narrowing of
      extracellular space accompanied by cytotoxic edema, and 2) delayed accumulation
      of exogenous 45Ca due to reduced clearance of extracellular fluid.

PMID- 7514759
TI  - Effect of cerebral arterial occlusion on cerebral perivascular innervation: a
      histochemical and immunohistochemical study in the rat.
AB  - The effect of acute cerebral occlusion on the distribution of cerebral
      perivascular nerves containing catecholamine, neuropeptide Y, and vasoactive
      intestinal peptide was studied in the three commonly used rat models of cerebral
      ischemia: Unilateral permanent middle cerebral artery (MCA) occlusion induced
      with an intraluminal thread technique; unilateral MCA occlusion produced by
      extraluminal electrocoagulation of the MCA; and transient arterial occlusion of
      the whole brain induced extracranially by the four-vessel clasp occlusion method
      for 30 minutes. Animals were sacrificed 3 days after occlusion and the
      distribution of the perivascular nerves of the MCA studied. Intraluminally
      occluded MCAs showed a similar distribution of perivascular nerves to those of
      contralateral and sham-operated MCAs. Extraluminally occluded MCAs demonstrated a
      marked decrease in perivascular nerves containing catecholamine and peptides
      while the contralateral MCAs showed normal distribution of the nerves.
      Extracranial occlusion caused no discernible change in the distribution of
      perivascular nerves in occluded and sham-operated animals. This study indicates
      that the different methods of cerebral arterial occlusion have variable effects
      on the perivascular innervation. Arterial occlusion induced by intraluminal or
      transient extracranial procedures does not impair cerebral perivascular
      innervation at least up to 3 days post-occlusion. In contrast, cerebral arterial
      occlusion by extraluminal electrocoagulation diminishes the perivascular nerves
      around the occluded cerebral artery.

PMID- 7514761
TI  - Factors influencing the recurrence rate of intracranial meningiomas after
      surgery.
AB  - The postoperative recurrence rate was examined in 242 patients with intracranial
      meningiomas to identify correlations with age, location, histology, or extent of
      surgery (Simpson's grade). There was no significant difference in the recurrence
      rate among the histological subtypes, but malignant meningiomas and
      hemangiopericytomas tended to recur earlier. Anterior basal meningiomas
      demonstrated a higher recurrence rate, but this depended on the feasibility of
      complete surgical removal. The recurrence rates significantly decreased in the
      order Simpson's grade I surgery, grade II or III surgery, and grade IV surgery (p
      < 0.001). These results indicate that the most important factor to influence
      recurrence is the extent of surgical removal.

PMID- 7514762
TI  - Strategies to improve the outcome of carotid endarterectomy.
AB  - The outcomes of carotid endarterectomy (CEA) including long-term results in 121
      patients (126 procedures) were retrospectively analyzed to identify the causes of
      operative morbidity. The angiographic internal carotid artery (ICA) stenosis was
      severe (> 70%) in 62 patients and moderate (50-70%) with ulceration in 64. The
      arterial wall was sutured primarily in 91 patients and with patch graft in 35.
      The outcomes 3 months after operation were good recovery in 86 patients,
      moderately disabled in 20, severely disabled in 11, and death in four. Three
      patients suffered operative morbidity (2.5%). During follow-up, three patients
      (2.6%) suffered transient ischemic attack on the operative side due to middle
      cerebral artery stenosis (50%) or ICA occlusion at the origin, and recurrent
      stenosis (40%) of the common carotid artery and ICA (1 each). In the latter two
      cases, the artery was primarily sutured. Improved therapeutic results require use
      of patch vein graft for the arterial wall suture, checking of the CEA patency,
      and prevention of intracranial ischemic events and hemorrhage due to associated
      lesions.

PMID- 7514763
TI  - Small gliomas: metabolism and blood flow.
AB  - Eight patients with small gliomas (6 low-grade and 2 high-grade) localized in a
      single gyrus or less than 2 cm diameter were investigated using positron emission
      tomography and single photon emission computed tomography. All three tumors
      examined demonstrated hypermetabolism of amino acids. High-grade gliomas
      demonstrated hypermetabolism of glucose and high blood flow, but normal or low
      oxygen metabolism. High-grade gliomas also showed accumulation of 201Tl chloride
      and high or low accumulation of 123I-isopropyl iodoamphetamine. These indications
      allow preoperative diagnosis of the malignancy of small gliomas, which is
      important because small gliomas with high-grade malignancy need more extensive
      removal and adjuvant therapy.

PMID- 7514764
TI  - Chronic subdural hematoma associated with middle fossa arachnoid cysts--three
      case reports.
AB  - Three patients with chronic subdural hematoma associated with middle fossa
      arachnoid cyst were treated by irrigating the hematoma through burr holes,
      because the symptoms were considered mainly due to increased intracranial
      pressure caused by the subdural hematoma. The symptoms disappeared immediately
      afterwards, so no surgery for the middle fossa arachnoid cyst was done. The
      patients were followed by magnetic resonance imaging. No subdural hematoma
      recurred during a postoperative period of 11 months to 2.5 years, and the
      arachnoid cyst reduced in size in two patients. We recommend irrigation of the
      subdural hematoma as the initial procedure of choice for such cases.

PMID- 7514765
TI  - Treatment of nongerminomatous germ-cell tumors of the pineal region.
AB  - Germ-cell tumors can be subdivided into germinoma, embryonal carcinoma,
      choriocarcinoma, endodermal sinus tumor (yolk-sac tumor), and teratoma. They are
      also distinguished by their production of secreted markers such as alpha
      fetoprotein produced in endodermal sinus tumors and embryonal carcinoma or beta
      human chorionic gonadotropin, produced by choriocarcinoma and embryonal
      carcinoma. Germinoma and teratoma produce none of the markers. Because it has
      been proposed that teratomas may differentiate from multipotent stem cells
      contained in embryonal carcinoma and are thus lineage related, the presence of
      markers indicates the presence of a nongerminomatous germ-cell tumor.
      Nongerminomatous germ-cell tumors are an invariably fatal subgroup within the
      pediatric pineal region germ-cell tumors. There is no effective, established
      therapeutic regimen. We report the treatment regimen for three children diagnosed
      with this highly aggressive tumor entity. The children were first given a course
      of chemotherapy with bleomycin, etoposide, and cisplatin. This resulted in the
      normalization of markers and the shrinkage of tumors. These were then removed by
      the infratentorial supracerebellar approach. Removal was followed by a second
      course of chemotherapy with vinblastine, ifosfamide, and cisplatin; after which
      the children underwent radiotherapy. All three children are well and without
      evidence of residual or recurrent disease 20, 30, and 32 months after surgery,
      respectively. We propose this therapy regimen for children in whom the markers
      are positive.

PMID- 7514767
TI  - N-methyl-D-aspartate receptor antagonist ketamine selectively attenuates
      spontaneous phasic activity of supraoptic vasopressin neurons in vivo.
AB  - Supraoptic neurosecretory neurons express a prominent N-methyl-D-aspartate
      receptor system. Recent in vitro evidence reveals that N-methyl-D-aspartate
      receptor activation dramatically alters the spontaneous discharge patterns of
      supraoptic neurons. In this study we evaluate whether N-methyl-D-aspartate
      receptors in vivo contribute to the development of characteristic phasic
      discharge patterns displayed by vasopressin-secreting neurons. Intravenous
      administration of ketamine hydrochloride, a non-competitive N-methyl-D-aspartate
      receptor antagonist, was used to examine whether N-methyl-D-aspartate receptor
      blockade influences patterned spontaneous discharge observed in supraoptic
      neurosecretory neurons. Extracellular recordings were obtained from identified
      hypothalamic supraoptic neurons in pentobarbital-anaesthetized Long-Evans rats.
      Systemic administration of ketamine (< or = 1.5 mg/kg) potently suppressed
      spontaneous phasic discharge in 16/19 putative vasopressin-secreting cells. The
      ketamine-induced blockade was dose dependent, fully reversible and was associated
      with the complete blockade of activity evoked by local pressure application of N
      methyl-D-aspartate, but not the activity evoked by alpha-amino-3-hydroxy-5-methyl
      isoxazole-4-propionate receptor agonists (6/6 cells). Ketamine had no detectable
      effect on threshold or shape of antidromic action potentials. By comparison, the
      activity in 9/10 continuously active neurons (putative oxytocin-secreting) was
      unaffected by administration of identical doses of ketamine. These data suggest
      that N-methyl-D-aspartate receptors play an important role in regulating the
      onset and maintenance of spontaneous phasic activity patterns displayed by rat
      supraoptic vasopressin neurons in vivo.

PMID- 7514766
TI  - Dynamics of synapsin I gene expression during the establishment and restoration
      of functional synapses in the rat hippocampus.
AB  - Synapse development and injury-induced reorganization have been extensively
      characterized morphologically, yet relatively little is known about the
      underlying molecular and biochemical events. To examine molecular mechanisms of
      synaptic development and rearrangement, we looked at the developmental pattern of
      expression of the neuron-specific gene synapsin I in granule cell neurons of the
      dentate gyrus and their accompanying mossy fibers during the main period of
      synaptogenic differentiation in the rat hippocampus. We found a significant
      difference between the temporal expression of synapsin I messenger RNA in dentate
      granule somata and the appearance of protein in their mossy fiber terminals
      during the postnatal development of these neurons. Next, to investigate the
      regulation of neuron-specific gene expression during the restoration of synaptic
      contacts in the central nervous system, we examined the expression of the
      synapsin I gene following lesions of hippocampal circuitry. These studies show
      marked changes in the pattern and intensity of synapsin I immunoreactivity in the
      dendritic fields of dentate granule cell neurons following perforant pathway
      transection. In contrast, changes in synapsin I messenger RNA expression in
      target neurons, and in those neurons responsible for the reinnervation of this
      region of the hippocampus, were not found to accompany new synapse formation. On
      a molecular level, both developmental and lesion data suggest that the expression
      of the synapsin I gene is tightly regulated in the central nervous system, and
      that considerable changes in synapsin I protein may occur in neurons without
      concomitant changes in the levels of its messenger RNA. Finally, our results
      suggest that the appearance of detectable levels of synapsin I protein in in
      developing and sprouting synapses coincides with the acquisition of function by
      those central synapses.

PMID- 7514768
TI  - ATP regulates synaptic transmission by pre- and postsynaptic mechanisms in guinea
      pig myenteric neurons.
AB  - Intracellular recordings were made from myenteric neurons of the guinea-pig ileum
      in vitro; they were classified into S and AH neurons according to
      electrophysiological criteria. ATP (10 nM-100 microM) inhibited excitatory
      synaptic potentials in the myenteric plexus; fast excitatory postsynaptic
      potentials and slow excitatory postsynaptic potentials of S neurons and slow
      excitatory postsynaptic potentials in AH neurons. This inhibitory action was
      reversible and dose-dependent, and was usually followed by a transient
      augmentation of the synaptic potentials after washing of ATP. The actions of ATP
      on the synaptic potentials were prevented by pretreatment with theophylline,
      caffeine, quinidine and 8-phenyl theophylline. The ATP analogues, ATP-gamma-s
      (100 nM-100 microM) and alpha-beta-methylene ATP (100 nM-100 microM) also
      depressed the synaptic potentials recorded from both types of neurons. The
      inhibitory effect of adenosine on the synaptic potentials was 10 times weaker
      than that of ATP. Thus, it seems clear that the presynaptic inhibition is not
      occurring through adenosine A1 or A2 receptors. Furthermore, ATP at high
      concentrations ( > or = 1 microM) augmented nicotinic fast depolarizations of S
      neurons produced by extracellular acetylcholine. However, ATP at the same
      concentrations inhibited the slow depolarizations of S and AH neurons caused by
      exogenous acetylcholine (muscarinic) and substance P. It is concluded that ATP
      regulates synaptic transmission in the myenteric plexus of the guinea-pig ileum
      and the sites of ATP actions are pre- and postsynaptic.

PMID- 7514769
TI  - Central distribution of substance P, calcitonin gene-related peptide and 5
      hydroxytryptamine in vagal sensory afferents in the rat dorsal medulla.
AB  - The central distribution of vagal afferents in the medulla containing either
      substance P, calcitonin gene-related peptide or 5-hydroxytryptamine was examined
      using a double-labelling technique and laser scanning confocal microscopy. Areas
      of the nucleus tractus solitarii, dorsal motonucleus of the vagus nerve and area
      postrema were scanned for double-labelled axon profiles. Analysis of this
      material revealed that all three neurochemicals were contained within the central
      terminals of vagal nerve sensory neurons. However, the distribution of vagal
      nerve afferents containing each of these putative transmitters differed.
      Afferents containing 5-hydroxytryptamine were detected mainly in the areas
      postrema and the adjacent nucleus tractus solitarii, with a smaller number in the
      ventral subnuclei of the solitary tract. In contrast afferents containing
      calcitonin gene-related peptide were found primarily in the medial and
      commissural regions of the nucleus tractus solitarii. Afferents containing
      substance P-immunoreactivity were surprisingly few in number and did not appear
      to be associated with any particular region. These results establish the presence
      of 5-hydroxytryptamine, substance P and calcitonin gene-related peptide in the
      central axons of vagal sensory afferents. Furthermore, the differential
      distribution of afferents immunoreactive for these neurochemicals seen in this
      study, together with previous demonstrations of the viscerotopic organization of
      vagal sensory afferents suggests a possible "chemical coding" for individual end
      organs.

PMID- 7514770
TI  - Double-staining of horizontal and amacrine cells by intracellular injection with
      lucifer yellow and biocytin in carp retina.
AB  - Horizontal and amacrine cells in the isolated carp retina were impaled with
      micropipette electrode, identified by their characteristic light responses, and
      injected iontophoretically with markers for morphological study. Both Lucifer
      Yellow CH and biocytin were injected simultaneously. Lucifer Yellow was seen by
      its own fluorescence while biocytin was visualized by binding with Texas Red
      linked or horseradish peroxidase-conjugated avidin. For cone-connected horizontal
      cells, biocytin-coupled cells were found to be approximately five-times more
      numerous than Lucifer Yellow-coupled cells. Coupling for both tracers was
      consistently hampered by intravitreally applied dopamine. In untreated retinas,
      the injected Lucifer Yellow was restricted within one rod-connected horizontal
      cell, while biocytin revealed several coupled neighbors. Amacrine cells, labeled
      by the tracers, were morphologically grouped into eight types, based on our
      earlier classification. Among them, amacrine cells, belonging to three types
      (Fnd, Pmb or Pma), were confirmed to be Lucifer Yellow-coupled, and the number of
      biocytin-coupled cells was more numerous (about 2.5 times) than that of Lucifer
      Yellow-coupled cells. Most amacrine cells (i.e. Pwd, Fnb and Fna) showed biocytin
      coupling with no Lucifer Yellow-coupling. A few classified (i.e. Pwb and Fwa) and
      unclassified cells did not show any coupling. Since the tracer coupling takes
      place via gap junctions, the majority of amacrine cells, belonging to certain
      homologous types, appear to be functionally coupled with each other in the inner
      plexiform layer. However, dopamine did not influence the range of tracer coupling
      between amacrine cells in the carp retina under the present experimental
      conditions.

PMID- 7514771
TI  - Opioid responsiveness of cancer pain syndromes caused by neuropathic or
      nociceptive mechanisms: a combined analysis of controlled, single-dose studies.
AB  - We performed a combined analysis of the results from four controlled single-dose
      relative-potency studies to assess the impact of inferred pain mechanism on the
      response to an opioid drug. A total of 168 patients received 474 administrations
      of either morphine or heroin, and we assessed the analgesic response during a 6
      hour period with visual analog scales. We summarized this as a total pain relief
      (TOTPAR) score. Two experienced pain clinicians reviewed information about pain
      characteristics and designated each case according to the inferred pain mechanism
      (neuropathic, nociceptive, or mixed) and the degree of confidence in the inferred
      mechanism (definite versus probable/possible). They grouped the cases as follows:
      nociceptive pain only (n = 205), neuropathic pain only (n = 49), and mixed (n =
      220). We compared pain relief achieved by patients with different mechanisms,
      with TOTPAR adjusted for significant covariates (duration of prior opioid
      administration, doses of opioid administered in the previous 48 hours, pain
      intensity at the start of the study, BUN:creatinine ratio, and dose of
      administered opioid). The adjusted mean TOTPAR score of the group with any
      neuropathic pain was significantly lower than that of the group with nociceptive
      pain only (26.1 versus 20.4, p = 0.02). The score of the group with definite
      nociceptive pain alone (adjusted mean TOTPAR = 28.0) was significantly higher
      than scores of the groups with possible/probable nociceptive pain (TOTPAR =
      19.9), mixed mechanisms (TOTPAR = 20.2), definite neuropathic pain alone (TOTPAR
      = 20.6), and possible/probable neuropathic pain alone (TOTPAR = 22.9).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7514772
TI  - Expression of endothelial leukocyte adhesion molecule-1 (ELAM-1) in chronic
      inflammatory demyelinating polyneuropathy.
AB  - We used immunocytochemical methods to identify activated endothelial cells and
      the ligands of infiltrating cells in sural nerve biopsies from 30 patients with
      peripheral neuropathy. In chronic inflammatory demyelinating polyneuropathy
      (CIDP), the endothelial leukocyte adhesion molecule (ELAM-1; E-selectin) was
      detected in the epineurial vessels of five of the 10 patients. CD68-positive
      monocytes were usually at ELAM-1-positive endothelial sites and in perivascular
      tissues, while sialyl-Lewis x-positive cells were detected mostly in the lumina
      adherent to ELAM-1-positive endothelial cells. The location of activated T cells
      was not correlated with activated endothelial cells, and endoneurial vessels were
      not immunostained for ELAM-1. In view of the transient expression of ELAM-1 in
      response to cytokine stimulation, these findings suggest that endothelial cells
      play a role in the extravasation of infiltrating cells in CIDP.

PMID- 7514774
TI  - Neurochemical profiles in cerebrospinal fluid of stroke-prone spontaneously
      hypertensive rats.
AB  - The purpose of the present study was to evaluate stroke-prone spontaneously
      hypertensive rats (SHRSP) neurochemically by determining the cerebrospinal fluid
      (CSF) levels of acetylcholine (ACh), norepinephrine (NE) and serotonin (5-HT) as
      an index of central neuronal activity. The CSF ACh levels of 15- to 20-week-old
      SHRSP were significantly lower than those of age-matched Wistar Kyoto rats (WKY)
      both under the urethane/alpha-chloralose anesthesia and in freely moving
      conditions. The difference in the CSF ACh levels between SHRSP and WKY was more
      marked at 30-40 weeks. Sustained changes were not observed in the CSF NE and 5-HT
      levels. Thus, the progressive dysfunction in the central cholinergic system may
      characterize the pathophysiological state of this animal model with cerebral
      lesions caused by continuous high blood pressure.

PMID- 7514773
TI  - Blockade of neurotensin receptors by the antagonist SR 48692 partially prevents
      retrograde axonal transport of neurotensin in rat nigrostriatal system.
AB  - The effect of SR 48692, a potent and selective non-peptide antagonist of the
      neurotensin receptor, was investigated on the retrograde axonal transport of
      neurotensin in the rat nigrostriatal dopamine pathway. When rats were injected in
      the striatum with (3-[125I]iodotyrosyl3)neurotensin, a substantial accumulation
      of radioactivity appeared in the ipsilateral substantia nigra 1.5 h after
      injection, and highest levels (336 +/- 23 dpm/mg of protein) were observed 2.5
      3.5 h after the injection. The phenomenon required a pretreatment of the animals
      with thiorphan (30 micrograms) an inhibitor of endopeptidase. The amount of
      radioactivity accumulated (3.5 h) was found to be reduced (25%) by local (100 nM)
      or peripheral administration of SR 48692 (5, 10, 20 mg/kg, i.p.; 25%, 40%, 40%,
      respectively). Our results indicate that blockade of neurotensin receptors by a
      selective non-peptide receptor antagonist affects the retrograde axonal transport
      of the tridecapeptide, and further suggest the notion that this process involves
      neurotensin receptors.

PMID- 7514775
TI  - Expression of inducible nitric oxide synthase in cytomegalovirus-infected glial
      cells of retinas from AIDS patients.
AB  - The inducible isoform of nitric oxide synthase has been detected in
      cytomegalovirus (CMV)-infected retinas from acquired immunodeficiency syndrome
      (AIDS) patients by immunohistochemistry and NADPH-diaphorase staining. Subsequent
      immunohistochemistry using antibodies against CMV antigens and glial fibrillary
      acidic protein (GFAP) demonstrated that inducible NOS was localized in CMV
      infected glial cells, particularly Muller cells. These findings indicate that
      inducible NOS is expressed in vivo in the human retina as a result of viral
      infection, and suggest that high levels of NO production might be involved in CMV
      induced retinitis.

PMID- 7514776
TI  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate and kainate differently
      affect neuronal cytoarchitecture of rat cerebellar granule cells.
AB  - Rat cerebellar granule cells cultured in media containing 12 mM KCl showed short
      life-span, did not branch, and died after 10 days in vitro. The cell exposure to
      N-methyl-D-aspartate (NMDA) or to kainate promoted both neuron survival and
      branching, reproducing the viability and the neurite extension routinely observed
      in cultures maintained in media containing 25 mM KCl. Exposure of neurons to
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) resulted in an
      increased survival not associated with neuritic arborization. These results
      suggest that the glutamate ionotropic receptor subtypes differently contribute in
      elaborating neuronal morphogenesis.

PMID- 7514777
TI  - Direct projections from the periaqueductal gray to the pontine micturition center
      (M-region). An anterograde and retrograde tracing study in the cat.
AB  - Micturition is a spino-bulbo-spinal reflex. The bulbospinal part of this reflex
      is formed by the projections from the M-region, also called the pontine
      micturition center or Barrington's nucleus, to the preganglionic parasympathetic
      motoneurons in the sacral cord innervating the bladder. In respect to the spino
      bulbar part of the micturition reflex, our group recently showed that the sacral
      cord projections to the brainstem terminate mainly in the periaqueductal gray
      (PAG). In this study it was investigated whether the PAG might serve as a link
      between the sacral cord and the M-region, by examining the possible connections
      using the tracers wheat germ-agglutin horseradish peroxidase and tritiated
      leucine. The results demonstrate that a specific circumscribed rostrocaudally
      oriented cell group within the ventrolateral PAG and parts of the dorsomedial PAG
      project specifically to the M-region. A concept is put forward in which specific
      parts of the PAG are involved in the control of micturition and that information
      concerning bladder filling is conveyed via the PAG to the M-region.

PMID- 7514778
TI  - Anatomical location of a taste-related region in the thalamic reticular nucleus
      in rats.
AB  - To locate a taste-related region in the thalamic reticular nucleus (Rt), we
      explored a reticular region having connections with the thalamic taste relay and
      the cortical taste area (CTA), by neuronal tracing methods using HRP, WGA-HRP and
      biocytin. Tracer injections at the thalamic taste relay, i.e., the parvicellular
      part of the thalamic posteromedial ventral nucleus (VPMpc), labeled cell bodies
      and axon terminals in a confined portion of the ipsilateral Rt. This was located
      at the ventromedial-most portion of the nucleus at the level of approx. 1.2 mm
      rostral to the rostral end of the VPMpc. Tracer injections at the CTA
      ipsilaterally labeled axon terminals in the same region of the Rt, as did the
      thalamic injections. When WGA-HRP was injected at this taste-related region in
      the Rt, we observed labeled cell bodies in layer VI in the CTA; in the VPMpc we
      saw densely labeled axon terminals but few, if any, labeled cell bodies. The
      results indicated that the taste-related region in the Rt receives input from the
      VPMpc and CTA, and sends output to the VPMpc. They also showed that the reticulo
      thalamic projections were much heavier than the thalamo-reticular ones in the
      taste system.

PMID- 7514779
TI  - Serum progesterone as a predictor of methotrexate success in the treatment of
      ectopic pregnancy.
AB  - OBJECTIVE: To determine the prognostic value of a single serum progesterone
      measurement for resolution of ectopic pregnancy following methotrexate therapy.
      METHODS: All patients attending our infertility clinic had quantitative beta-hCG
      and serum progesterone measured prospectively within the first week of missed
      menses. Ectopic pregnancy was diagnosed nonsurgically by poorly rising beta-hCG
      levels and lack of evidence of intrauterine gestation by transvaginal sonography.
      Once diagnosed, candidates received a single intramuscular injection of
      methotrexate, 50 mg/m2. Treatment outcome was categorized as either resolved or
      requiring surgery, and interpreted with respect to serum progesterone measured
      within 24 hours of methotrexate administration. RESULTS: Twenty-one patients were
      treated for ectopic pregnancy. Eleven had serum progesterone levels greater than
      10 ng/mL and ten patients had levels of 10 ng/mL or less. The two groups did not
      differ significantly with respect to age, weight, hCG at the time of methotrexate
      administration, or amount of methotrexate administered. Of the 11 patients with
      serum progesterone levels above 10 ng/mL, only five had pregnancies that resolved
      following methotrexate. All ten patients with levels less than 10 ng/mL had
      resolution. This difference is significant (P = .009, 95% confidence interval
      0.26-0.84). There was no improvement in the prediction of outcome when either the
      absolute or daily percentage increase of hCG was determined before methotrexate
      administration. CONCLUSION: A single serum progesterone measurement above or
      below 10 ng/mL is useful for predicting resolution of tubal pregnancy with
      methotrexate treatment.

PMID- 7514780
TI  - Effect of pH and CO2 on in vitro susceptibility of Pseudomonas cepacia to beta
      lactams.
AB  - Inhibition of Pseudomonas cepacia (but not Pseudomonas aeruginosa) by beta
      lactams was decreased in 5% CO2 in air compared with air alone. The effect of CO2
      and pH (range, 6.0 to 8.0) on beta-lactam susceptibility, beta-lactamase
      expression, and outer membrane proteins was studied in isolates recovered from
      the sputum of children with cystic fibrosis. Incubation in 5% CO2 decreased the
      activity of piperacillin, piperacillin/tazobactam, and ceftazidime, although
      isolates were still clinically sensitive (minimum inhibitory concentrations < 16
      mg/L). Cefpirome activity was markedly decreased from a minimum inhibitory
      concentration of 2.0 to greater than 64 mg/L. On highly buffered 3-(N-morpholino)
      propane sulfonic acid media, beta-lactam susceptibility was eliminated at pH
      greater 7.5. A 2- to 13-fold increase in beta-lactamase activity was demonstrated
      after growth in 5% CO2 compared with basal aerobic levels for 13 of 15 clinical
      isolates. beta-Lactamase activity did not vary significantly with pH. Addition of
      imipenem to media (2.0 mg/L) resulted in hyperproduction of beta-lactamase (180
      fold). Isoelectric points varied with cultural conditions, and all beta
      lactamases detected were inhibited by clavulanate and tazobactam. Significant
      hydrolysis of piperacillin and ceftazidime could not be demonstrated. A 36-kD
      porin was present at all pH tested. Thus, our strains of Pseudomonas cepacia were
      markedly affected by cultural conditions not normally used in standardized
      susceptibility tests. However, such conditions may be encountered in the
      pathologically altered infected lung in cystic fibrosis.

PMID- 7514781
TI  - Effect of recombinant stem cell factor on clonogenic maturation and cycle status
      of human fetal hematopoietic progenitors.
AB  - Studies were undertaken to delineate the actions of stem cell factor (SCF) on
      human fetal hematopoietic progenitors in vitro. Mononuclear cells from umbilical
      cord blood of term fetuses were "panned" immunologically, and the resulting
      hematopoietic progenitors were grown in methylcellulose culture containing
      various concentrations of SCF alone or in combination with other recombinant
      hematopoietic growth factors. Neutralizing antibodies to IL-3 and granulocyte
      macrophage colony-stimulating factor were added to all plates to which
      recombinant IL-3 or granulocyte-macrophage colony-stimulating factor were not
      included to decrease any confounding effect resulting from production of small
      quantities of these factors within the culture plates. SCF, as a single agent,
      supported clonogenic maturation of fetal granulocyte-macrophage progenitors
      (granulocyte-macrophage colony-forming unit, p < 0.05), multipotent progenitors
      (CFU-MIX, p < 0.05), and erythroid progenitors (erythroid burst-forming unit, p <
      0.05). When combined with subplateau concentrations (0.1 microgram/L) of IL-3 or
      granulocyte-macrophage colony-stimulating factor, SCF had an additive or
      synergistic effect on clonogenic maturation of granulocyte-macrophage colony
      forming unit and CFU-MIX. When combined with higher concentrations (5.0
      micrograms/L) of IL-3 or granulocyte-macrophage colony-stimulating factor, SCF
      generally did not enhance colony formation but did increase the number of cells
      per colony. Like other pleiotropic cytokines such as IL-6, IL-9, and IL-11, SCF
      had a broad spectrum of action of fetal hematopoietic progenitors.

PMID- 7514782
TI  - Prevalence of hepatitis C virus in a chronic care facility.

PMID- 7514783
TI  - Rubella infection after orthotopic liver transplantation.

PMID- 7514784
TI  - Post extracorporeal membrane oxygenation single photon emission computed
      tomography (SPECT) as a predictor of neurodevelopmental outcome.
AB  - OBJECTIVE: To determine the incidence and site of single photon emission computed
      tomography scan (SPECT) abnormalities in survivors of neonatal extracorporeal
      membrane oxygenation and to evaluate the efficacy of SPECT scan as a predictor of
      neurodevelopmental outcome in these infants. SETTING: Tertiary care neonatal
      intensive care unit in Detroit, MI. PATIENT POPULATION: Survivors of neonatal
      extracorporeal membrane oxygenation who had a SPECT scan of the brain performed
      after decannulation and before their discharge from the neonatal intensive care
      unit were included if they had at least 12 months of follow-up in our
      developmental assessment clinic. OUTCOME MEASURES: The neurological outcome was
      reported as normal, suspect, and abnormal on the basis of neurological
      examination and developmental milestones. The developmental outcome was assessed
      by Bayley mental development index or McCarthy general cognitive index scores.
      RESULTS: A total of 59 patients met study criteria. SPECT scan abnormalities were
      noted in 45 (76%) infants. Global hypoperfusion was the most frequent abnormality
      followed closely by bilateral focal perfusion defects. The distribution of
      perfusion abnormalities was not significantly different for right and left
      hemispheres. Among 14 infants with normal SPECT scans, 13 infants had normal
      neurological outcome and all had a normal developmental outcome. Of the 45
      infants with an abnormal SPECT scan, 7 infants had an abnormal neurological
      outcomes and 4 infants had an abnormal developmental outcome. SPECT scan
      abnormalities had no significant correlation with neurodevelopmental outcome of
      these infants. CONCLUSION: Although a normal SPECT scan was more likely to
      predict a normal neurodevelopmental outcome, an abnormal SPECT scan did not
      predict an abnormal outcome in these infants.

PMID- 7514786
TI  - Effect of template secondary structure on the inhibition of HIV-1 reverse
      transcriptase by a pyridinone non-nucleoside inhibitor.
AB  - The importance of RNA secondary structure on HIV-1 reverse transcriptase
      catalyzed polymerization and on the potency of the pyridin-2-one inhibitor 3-(4,7
      dichlorobenzoxazol-2-ylmethylamino)-5-ethyl-6-meth ylpyridin-2(1H)-one, L
      697,661, were investigated by employing heteromeric primer-template systems. Our
      data revealed that a stem-loop hairpin secondary structure in the RNA template
      could lead to strong hindrance of reverse transcription in the reaction catalyzed
      by HIV-1 reverse transcriptase resulting in the build up of intermediate-length
      (pause) polymerization products. The presence of L-697,661 greatly enhanced the
      accumulation of the pause products suggesting that the rate of enzyme
      translocation from the pause product might be more potently inhibited than
      polymerization up to the pause site. Model experiments using a synthetic RNA
      template containing a stem-loop hairpin revealed that the inhibitory potency of L
      697, 661 increased 2-fold upon polymerization to within four bases of the
      secondary structure. Inhibitor potency was enhanced over 6-fold when primer
      extension proceeded through the duplex region of the stem-loop.

PMID- 7514787
TI  - Theoretical studies of DNA-RNA hybrid conformations.
AB  - Molecular modelling has been used to probe the conformational preferences of
      double stranded DNA-RNA hybrids. As might be expected, the sugars of the DNA
      strand have higher conformational flexibility, but, for the majority of the
      repetitive sequences studied, these sugars prefer a C2-endo pucker, while ribose
      sugars uniformly adopt a C3-endo pucker. This gives rise to a strongly
      heteronomous duplex conformation. One exception to this rule involves the
      thymidine strand of poly(dT).poly(rA), which marginally prefers a C3-endo pucker.
      Our study further indicates that the DNA strands of the hybrids favour backbone
      torsions in the canonical B domain, rather than the modified values proposed on
      the basis of fibre diffraction studies. Backbone conformational transitions can
      nevertheless be induced leading to an alpha gamma-flip (alpha:gamma, g-/g(+)-
      >t/t) or to the alpha beta gamma-flip form proposed from fibre studies
      (alpha:beta:gamma, g-/t/g(+)-->t/g+/t). The latter transition is also found to be
      linked to BI-->BII transitions (epsilon:zeta, t/g(-)-->g-/t).

PMID- 7514789
TI  - Purification and characterization of acute phase rat plasma thiostatin.
AB  - Thiostatin was purified from acute phase plasma of turpentine-treated rats by a
      novel, single-step carboxymethyl-papain Sepharose 4B column chromatographic
      procedure. Purified thiostatin appeared as a single band in SDS-PAGE with an
      estimated molecular weight of 68,000. Western blot with polyclonal rabbit anti
      thiostatin IgG confirmed a homogeneous immuno-reactive 68 kDa species. Specific
      activity, as determined by enzyme-linked immunosorbent assay (ELISA), was 0.972
      mg kininogen equivalent per mg protein. The yield of thiostatin exceeded 60% and
      the protein was purified 10.7-fold.

PMID- 7514788
TI  - Editing of Trypanosoma brucei maxicircle CR5 mRNA generates variable carboxy
      terminal predicted protein sequences.
AB  - RNA editing post-transcriptionally modifies several mRNAs from the maxicircle of
      kinetoplastid parasites by addition and removal of uridine residues. We report
      here that maxicircle CR5 transcripts of Trypanosoma brucei are edited in two
      domains separated by an eight nucleotide sequence that remains unedited. The
      large 5' domain is edited to a consensus sequence while the smaller 3' domain is
      edited to multiple final sequences. In all, 205-217 Us are inserted and 13-16
      encoded uridines are deleted from the CR5 mRNA, producing a mature transcript 75
      80% larger than the unedited transcript. The edited RNAs predict small, highly
      hydrophobic proteins. The carboxy terminal 15-30% of these predicted proteins
      have multiple different amino acid sequences as a result of the variable edited
      3' mRNA sequence, but these fall into two families of sequence. Limited amino
      acid sequence and hydrophobicity profile similarities suggest that the protein
      encoded by edited CR5 mRNA may be a subunit of NADH dehydrogenase.

PMID- 7514790
TI  - Deleterious effect of dithizone-DMSO staining on insulin secretion in rat and
      human pancreatic islets.
AB  - Dithizone (DTZ) is a selective stain for pancreatic islets which facilitates
      their identification, being of special interest in human islet isolation
      assessment. Nevertheless, there are few studies concerning its potential toxic
      effects on islet function. In our study, we have evaluated the effects of DTZ
      (dissolved in dimethyl sulfoxide [DMSO] 1% w/v) at three different concentrations
      (2, 10, and 100 micrograms/ml) on insulin response to glucose in human and rat
      islets. Likewise, we studied the effect of incubation time, in the presence of
      DTZ at the above-mentioned concentrations, on insulin release. Only when DTZ was
      employed at low concentrations and for a short period of incubation (10 min) was
      there no impairment of pancreatic islet function. Moreover, even at this low
      concentration, DTZ became deleterious for islet function when the incubation
      period with the dye was prolonged for 30 min. Culture (24 h) of previously
      stained islets produced a partial recovery of insulin response. In conclusion,
      our findings indicate (a) DTZ should not be employed to collect islets for
      functional studies because of its deleterious effect on beta-cell function, (b)
      DTZ's deleterious effects on beta-cell function should be considered if this dye
      is used to purify islets by fluorescence-activated cell sorting for
      transplantation.

PMID- 7514792
TI  - Exocrine pancreatic proteins in serum during pancreatic allograft rejection.
AB  - The serum concentrations of immunoreactive pancreatic secretory trypsin
      inhibitor, cationic elastase, anionic trypsin, cationic trypsin, and total
      amylase activity, were studied after pancreatic allograft transplantation. Nine
      patients received whole organ pancreaticoduodenal allografts with exocrine
      drainage to the bladder. Eight of the patients received simultaneously a renal
      allograft. The serum concentration of immunoreactive cationic elastase increased
      gradually during the first postoperative days to a peak on the fifth day after
      surgery; all other proteins decreased in concentration after the first day.
      Eighteen episodes of pancreatic and/or kidney rejection, diagnosed by means of
      kidney biopsy, urinary cytology, kidney function, and urinary amylase levels,
      were analyzed. The pancreatic proteins displayed different patterns in serum
      concentration during the days immediately before diagnosis of rejection. The
      pancreatic secretory trypsin inhibitor showed the most pronounced peak in serum
      concentration during rejection and even reacted during some episodes without a
      decline in urinary amylase output. Cationic elastase on the other hand showed no
      reaction at all. From this homogeneous material it is possible to conclude that
      changes in serum concentrations during rejection are not the same for all
      pancreatic exocrine proteins.

PMID- 7514791
TI  - Effect of L-364,718 (CCK receptor antagonist) on exocrine pancreatic secretion of
      hydrocortisone-treated rats.
AB  - Exocrine pancreatic function was studied in control rats and animals subjected to
      treatment with hydrocortisone (10 mg/kg/day) over 7 days. In both cases, the
      cholecystokinin (CCK) receptor antagonist L-364,718 (0.1 mg/kg/day) had been
      administered. The administration of this nonpeptide CCK antagonist significantly
      reduced the basal pancreatic flow of secretion and enzymes in the control rats
      but did not cause a decrease in pancreatic weight. From this it may be inferred
      that factors other than CCK are able to exert the trophic effects of this
      hormone. Also, the processes of enzyme synthesis and storage, which contribute to
      maintaining the weight of the organ, continued to occur under conditions of
      deprivation of the action of endogenous CCK because pancreatic secretion in
      response to the infusion of CCK was similar in the animals treated and not
      treated with L-364,718. In contrast, no significant changes were observed either
      regarding pancreatic weight or basal pancreatic secretion in the animals treated
      with hydrocortisone and simultaneously with L-364,718, as compared with the rats
      treated only with hydrocortisone. This points to a predominant effect of
      glucocorticoids on the action of CCK during the phases of enzyme synthesis and
      storage, accompanied by a blockade of exocytosis due to hydrocortisone treatment.
      The secretagogue effect of CCK alone becomes possible with high levels of this
      hormone of exogenous origin, whose interaction with its specific receptors is in
      turn positively modulated by an excess of glucocorticoids.

PMID- 7514785
TI  - Arrays of complementary oligonucleotides for analysing the hybridisation
      behaviour of nucleic acids.
AB  - Arrays of oligonucleotides corresponding to a full set of complements of a known
      sequence can be made in a single series of base couplings in which each base in
      the complement is added in turn. Coupling is carried out on the surface of a
      solid support such as a glass plate, using a device which applies reagents in a
      defined area. The device is displaced by a fixed movement after each coupling
      reaction so that consecutive couplings overlap only a portion of previous ones.
      The shape and size of the device and the amount by which it is displaced at each
      step determines the length of the oligonucleotides. Certain shapes create arrays
      of oligonucleotides from mononucleotides up to a given length in a single series
      of couplings. The array is used in a hybridisation reaction to a labelled target
      sequence, and shows the hybridisation behaviour of every oligonucleotide in the
      target sequence with its complement in the array. Applications include sequence
      comparison to test for mutation, analysis of secondary structure, and
      optimisation of PCR primer and antisense oligonucleotide design.

PMID- 7514794
TI  - Enhancement of pancreatic secretion by dietary protein in rats with chronic
      diversion of bile-pancreatic juice from the proximal small intestine.
AB  - The regulation of exocrine pancreatic enzyme secretion by dietary protein is
      known to depend on pancreatic protease activity in the lumen of the proximal
      small intestine in rats, which is a negative feedback mechanism. We observed
      whether dietary protein stimulates pancreatic secretion in rats with a 7-day
      diversion of bile-pancreatic juice (BPJ) from the proximal small intestine under
      unrestrained and unanesthetized conditions. In the chronically BPJ-diverted rats,
      hypersecretion of proteases in the fasting state were observed, and pancreatic
      enzyme secretion was significantly increased after feeding of a 25% casein diet
      over the hypersecretion in the fasting state. The amplitude of the increments of
      the secretion after feeding in diverted rats was comparable to that in normal
      rats. Dietary fat decreased stimulated secretion by the protein diet in the
      diverted rats, but not in the normal rats. We conclude that there is an upper
      small intestinal BPJ-independent mechanism for response of pancreatic enzyme
      secretion to dietary protein, and that dietary fat inhibits pancreatic secretion
      in diverted rats. The distal small intestine or colon may contribute to the
      inhibition.

PMID- 7514793
TI  - Effects of galanin on amylase secretion from dispersed rat pancreatic acini.
AB  - Dispersed rat pancreatic acini were used to determine the effect of galanin on
      the exocrine pancreas and on basal and secretagogue-stimulated amylase secretion.
      Basal amylase secretion and amylase release stimulated by cholecystokinin
      octapeptide, bombesin, 12-o-tetradecanoyl-phorbol-13-acetate (TPA), secretin, and
      vasoactive intestinal peptide were not affected by galanin in doses ranging from
      10(-12) to 10(-6) M. Galanin, however, significantly inhibited the amylase
      release stimulated by sub- and supramaximal doses of carbachol. A time course
      study showed that the inhibition by galanin occurred during the sustained phase
      of carbachol-stimulated amylase secretion. The inhibitory action of galanin
      disappeared in acini obtained from animals pretreated with pertussis toxin (PTX).
      These results suggest that galanin inhibits carbachol-stimulated amylase
      secretion through a mechanism related to a PTX-sensitive G protein.

PMID- 7514795
TI  - Comparison of neurokinin substance P with morphine in effects on food-reinforced
      operant behavior and feeding.
AB  - In the present study, substance P (SP) was injected intraperitoneally (IP), and
      its effects on operant behavior were assessed in rats, which had been trained to
      bar press for food reward on a fixed-ratio (FR) 20 schedule. These effects were
      compared with IP injection of morphine sulfate, which had previously been shown
      to strongly suppress operant responding on FR schedules. The IP injection of SP
      resulted in a dose-related decrement in response rates. SP in a dose range of 250
      500 micrograms/kg decreased operant responding, whereas SP in a dose range of 5
      50 micrograms/kg did not influence response rates. The IP injection of morphine
      (10 mg/kg) markedly suppressed operant responding. However, in contrast to the
      rate-decreasing effects of SP, this suppression was not selective for the
      reinforced lever as responding on the nonreinforced lever, used as a control, was
      also decreased. Furthermore, both injection of 10 mg/kg morphine and SP in a dose
      range of 250-500 micrograms/kg was found to reduce food intake when the animals
      had free access to food subsequent to the operant conditioning session. The
      present results provide the first evidence that systemically administered
      neurokinin SP can affect operant responding for food reward. The suppressive
      effects on operant behavior and feeding obtained with systemic SP or morphine are
      discussed with respect to recent findings showing that both drugs can modulate
      mesolimbic dopamine activity after systemic drug injection.

PMID- 7514796
TI  - [Plasma proteins as biochemical markers of alcohol abuse].
AB  - Fractions of plasma proteins were marked in 135 alcohol dependent men. The
      increase in the level of beta globulins was found in 58%, a fall in the level of
      gamma globulins was found in 52% and in 26% of patients a fall in the level of
      albumin was recorded. Patients with a shorter period of dependence more
      frequently showed a lowering of the concentration of gamma globulin (59% of
      cases). Persons with a greater pathological pattern of dependence, however,
      showed an increase in the level of beta globulin (65% of cases). The joint use of
      beta globulin and gamma globulin as markers of alcohol abuse allowed for the
      detection of irregularities in the range of at least one of the above mentioned
      markers in 84% of the patients. The joint use of albumin, beta globulin and gamma
      globulin showed irregularities in at least one of these three tests in 90% of the
      patients. The authors conclude that marking the changes in the fraction of plasma
      proteins may be used as a biochemical marker of alcohol abuse.

PMID- 7514799
TI  - Immunoreactivity for diazepam binding inhibitor in Gomori-positive astrocytes.
AB  - A polypeptide termed diazepam binding inhibitor (DBI), capable of binding to
      receptor sites on glial mitochondria, is known to be present in glial cells and
      is particularly abundant in areas near circumventricular organs of the brain such
      as the arcuate nucleus of the hypothalamus. DBI appears to stimulate steroid
      synthesis and/or transport in glial mitochondria. The arcuate nucleus also
      contains large numbers of specialized glia, termed Gomori-positive astrocytes,
      that are estrogen-sensitive and which possess highly stained, heme-containing
      cytoplasmic granules. This study was performed to determine if these Gomori
      positive astrocytes are immunoreactive for DBI. A rabbit antibody to DBI, but not
      pre-immune serum, stained Gomori-positive glia and suggests that these glia are
      partly responsible for the high levels of DBI in circumventricular organs. DBI in
      these glia may be related to functional responses of the hypothalamus to steroid
      hormones.

PMID- 7514798
TI  - Peptide-containing nerve fibers in the parathyroid glands of different species.
AB  - Several neuropeptides, calcitonin gene-related peptide (CGRP), galanin,
      neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP),
      substance P (SP), vasoactive intestinal polypeptide (VIP), the noradrenergic
      marker dopamine beta-hydroxylase (DBH) and the general neuroendocrine marker PGP
      9.5 were localized by immunocytochemistry in the parathyroid glands of chicken,
      rat, guinea-pig, cat, dog and sheep. The general density of innervation varied
      markedly among the species. Nerve fibers storing CGRP, NPY, PACAP, SP and VIP
      were present in all species examined. Galanin-containing fibers occurred in all
      species except guinea-pig and adrenergic (DBH-containing) fibers in all species
      except chicken and guinea-pig. Generally, the nerve fibers were distributed
      around blood vessels, in the parenchyma as single scattered fibers, and often
      also within the capsule. Coexistence studies were performed in cat and sheep.
      CGRP and SP invariably coexisted in the same nerve fibers. Further, CGRP
      partially coexisted with PACAP, NPY was observed in the same nerve fibers as DBH.
      A small population of NPY-containing fibers also seemed to contain galanin (cat
      only). VIP and NPY coexisted in a population of nerve fibers in the parenchyma. A
      population of VIP-containing fibers also seemed to contain PACAP. The results
      indicate the presence of several neuropeptides in the parathyroid glands. As
      judged by their distribution patterns they may regulate both secretory activity
      and blood flow, some of them possibly in a cooperative manner.

PMID- 7514797
TI  - Pro-opiomelanocortin (POMC) gene expression, as identified by in situ
      hybridization, in purified populations of interstitial macrophages and Leydig
      cells of the adult rat testis.
AB  - The presence of testicular pro-opiomelanocortin (POMC) mRNA and POMC-derived
      peptides has recently been demonstrated in purified preparations of interstitial
      macrophages and in Leydig cells of the adult rat testis by Northern blot analysis
      and immunocytochemistry. In the present study, in situ hybridization provided
      further evidence that the POMC gene is expressed by both purified interstitial
      macrophages and Leydig cells. The cellular localization of the POMC transcripts
      was similar for both cell types, silver grains being predominantly located in the
      cytoplasm. The specificity of the labelling was demonstrated by the lack of
      silver grains in the preparations pretreated with RNAase or hybridized with an
      insulin cDNA probe, a gene known not to be expressed in these cell types. An
      additional control was provided by hybridization with a sense POMC RNA probe,
      which gave a less intense signal when compared with the antisense RNA probe under
      the same experimental conditions. The results confirm POMC gene expression in
      both macrophages and Leydig cells in the adult rat testis.

PMID- 7514800
TI  - Quantitation of N-terminally extended tachykinins in cerebrospinal fluid from
      healthy subjects.
AB  - N-terminally extended substance P (SP) and neuropeptide K (NPK), an N-terminally
      extended form of neurokinin A (NKA), were determined in cerebrospinal fluid (CSF)
      from healthy human subjects by combined high performance liquid chromatography
      and radioimmunoassay. The concentrations of the peptides were similar in fresh
      CSF and in CSF which had been kept frozen for up to 5 months. SP and NKA were not
      present in measurable amounts in neither fresh CSF nor in CSF that had been
      frozen. On the other hand, when synthetic SP and NKA were added to approx. 2 pM
      concentration to fresh CSF samples, both peptides were recovered to 85 and 98%,
      respectively. There were no significant concentration gradients of the peptides
      in the first 18 ml (three consecutive 6 ml fractions) of CSF (n = 10). In
      contrast, we confirmed previous findings, that there are gradients of the amine
      metabolites 5-HIAA (P < 0.01) and HVA (P < 0.001) (n = 5). The concentrations of
      extended SP (expressed in SP equivalents) and NPK in the first 6 ml of CSF were
      1.5 +/- 0.7 pM and 14.2 +/- 6.4 pM (mean +/- S.D., n = 10), respectively. The
      present results thus show that the levels of N-terminally extended SP and NKA are
      stable in frozen CSF samples for up to 5 months. The virtual lack of SP and NKA
      in CSF does not seem to be due to losses during sample preparation or storage.

PMID- 7514801
TI  - Amylin (islet amyloid polypeptide) inhibition of insulin release in the perfused
      rat pancreas: implication of the adenylate cyclase/cAMP system.
AB  - Amylin inhibits glucose-induced insulin secretion in the rat pancreas. To study
      the mechanism by which amylin acts on the B-cell, we have investigated, in the
      perfused rat pancreas, the effect of synthetic rat amylin (75 pM) on insulin
      release elicited by secretagogues acting on the B-cell via the adenylate
      cyclase/cAMP system, i.e., glucagon (10 nM), gastric inhibitory polypeptide (GIP,
      1 nM), forskolin (1 microM) and isobutylmethylxanthine (IBMX, 75 microM). In
      addition, we examined the effect of amylin on GIP-induced insulin release in
      pancreata from rats pretreated with pertussis toxin, an agent which inactivates
      certain Gi proteins coupled to adenylate cyclase. Amylin inhibited the insulin
      response to glucagon (approx. 70%), GIP (approx. 90%), IBMX (approx. 75%) as well
      as the early phase of forskolin-induced insulin output (approx. 74%). However,
      amylin failed to modify GIP-induced insulin release in pancreata obtained from
      pertussis toxin pretreated rats. These results would indicate that the inhibitory
      effect of amylin on insulin secretion could be, at least in part, attributed to
      its interfering with the adenylate cyclase/cAMP system. Furthermore, prevention
      of the inhibitory effect of amylin on GIP-induced insulin output by pertussis
      toxin pretreatment, supports the concept that amylin can inhibit insulin release
      via a pertussis toxin-sensitive Gi protein coupled to the adenylate cyclase
      system.

PMID- 7514802
TI  - Monoclonal antibodies to Brucella rough lipopolysaccharide: characterization and
      evaluation of their protective effect against B. abortus.
AB  - We characterized 4 monoclonal antibodies (mAb) specific for rough
      lipopolysaccharide (R-LPS) of Brucella. mAb were selected by enzyme-linked
      immunosorbent assay (ELISA) on whole B. abortus 45/20 rough cells and R-LPS from
      B. melitensis B115 rough cells. Specificity was confirmed by immunoblot analysis
      using R-LPS and smooth LPS (S-LPS) preparations. Anti-R-LPS revealed the low
      molecular mass R-LPS molecules below 20.1 kDa in the R-LPS and S-LPS preparations
      as well as the typical A and M patterns in high molecular mass S-LPS molecules
      (between 21.5 and 66 kDa) in the S-LPS preparations. An O-polysaccharide-specific
      mAb revealed only high molecular mass S-LPS molecules in the S-LPS preparation.
      In ELISA the anti-R-LPS mAb bound better on rough than on smooth B. abortus 544
      whole cells, and this was confirmed by immunoelectron microscopy. Protective
      activity of anti-R-LPS mAb of different isotypes was tested on mice and compared
      with an S-LPS-specific mAb. Only the IgG3 mAb reduced significantly the splenic
      infection but did not reach the level of protection conferred by the S-LPS
      specific mAb.

PMID- 7514803
TI  - Immunohistochemical localisation of cytokeratin and vimentin intermediate
      filament proteins in canine mammary tumours.
AB  - Monoclonal antibodies to human stratifying keratin (StK), simple keratin (SK),
      broad spectrum keratin (BSK) and vimentin were applied to 47 canine mammary
      tumours (three benign hyperplasia, 26 benign mammary tumours, one malignant mixed
      tumour, two malignant complex tumours, seven lobular carcinomas, three papillary
      carcinomas and five squamous cell carcinomas). In benign hyperplasia the SK
      antibody reacted with acinar and duct epithelial cells; the StK and BSK
      antibodies reacted strongly with duct epithelial cells in the canine mammary
      tumours expressed mainly keratins of stratified epithelia rather than those of
      simple epithelia. Myoepithelial cells in complex and mixed tumours can express
      StK and vimentin. The finding might be helpful in the assessment of complex
      tumours where stromal reactions may be confused with myoepithelial neoplastic
      proliferation. Stromal mesenchymal tissues, including precartilage in complex
      tumours, and clearly differentiated myoepithelial cells always stained positively
      for vimentin. Occasional carcinoma cells stained positively for vimentin.

PMID- 7514804
TI  - [Combination of antimycotic preparations and natural proteinase inhibitors in
      otomycosis].
AB  - In vitro experiments, Terrilytinum* increases the antimycotic activity of
      Clotrimazolum* and Nitrofungin*, and cancels out the inhibitory effect of
      Contrycal*. The combined application of Clotrimazolum and Nitrofungin with
      Terrilytinum and Contrycal as treatment of otomycosis of the middle ear has an
      outstanding clinical and anti-mycotic efficacy. The results of the investigation
      show that the proposed method of treatment is marked by an excellent therapeutic
      efficacy in the case of otomycosis.

PMID- 7514807
TI  - The riboskeleton: the "brain" of the cell?
AB  - The complexity of the RNA world has surprised biologists many times in recent
      years and has led, among other things, to a new definition of a gene. Its
      implications, however, may go even further than that. It is possible that the
      ribonucleoproteins form an information processing system which functions as the
      "brain" of the cell.

PMID- 7514805
TI  - [Lack of in vitro effect of antithyroid drugs upon peroxidase antigen expression
      in autoimmune thyroid disease].
AB  - The aim of this study is to determine whether antithyroid drugs (ATD) act via
      inhibiting thyroid hormone synthesis or by interfering with the immune process
      which leads to autoimmune disease. Previously we had demonstrated that ATD do not
      affect HLA-DR and TPO antigen expressions induced by appropriate stimulus in
      normal thyrocytes, so we decided to study what happens when the same experiments
      are performed using autoimmune thyrocytes. Cultured thyroid tissue from patients
      operated on for Graves' Disease or Hashimoto's Thyroiditis were stimulated with
      TSH or TBII alone or associated with ATD; TPO antigen expression was evaluated by
      the Cytotoxicity Assay using human monoclonal antiTPO. When autoimmune thyrocytes
      were cultured and no stimulus was used or with the addition of MMI or PTU alone,
      very low values of TPO expression were noted (8.6 +/- 6.7, 5.0 +/- 7.1 and 4.2%
      +/- 2.3% respectively); if they were stimulated with TSH or TBII, a sharp rise of
      TPO antigen expression was detected (54.4 +/- 23.3 and 62.6 +/- 16.5%), these
      figures being significantly different from unstimulated cells (p < 0.001). If
      both stimulus were used associated with ATD, the high TPO antigen expression was
      unaffected. It is concluded that, at least in vitro, ATD have no effect upon
      induced-antigen expression in autoimmune thyrocytes. Since they do not alter
      antigen presentation, a primary step in the immune process, it is difficult to
      accept that their mechanism of action is through interference with the immune
      response.

PMID- 7514806
TI  - [Prevalence of hepatitis C virus antibodies in chronic hemodialysis and kidney
      transplantation patients].
AB  - Hepatitis C virus antibodies were measured in 26 chronic hemodialyzed patients
      and 43 kidney transplant recipients, using a second generation ELISA method.
      Fifty four percent of hemodialyzed had a longer duration of dialysis treatment
      compared with patients with negative antibodies (57.6 +/- 30.5 vs 15.4 +/- 7.3
      months), and did not differ in the number of transfusions. Seven patients had
      elevated serum transaminase values, all with positive antibodies. Thirty five
      percent of kidney transplant recipients had positive antibodies. In these
      subjects, no relation was observed between the number of transfusions or length
      of dialysis treatment and the presence of positive hepatitis C antibodies.

PMID- 7514808
TI  - Activation signal induces the expression of B cell-specific CD45R epitope (6B2)
      on murine T cells.
AB  - T lymphocytes express multiple forms of the leukocyte-common antigen CD45,
      transcribed by alternative usage of leukocyte-common antigen exon 4-6. The
      various isoforms of CD45R expressed differentially on T cells are involved in
      different stages of development and activation. The monoclonal antibody (MoAb)
      RA3-6B2 is established as a B cell-type isoform (B220)-specific marker. However,
      it reacts with certain activated T cells although the relationship between 6B2
      expression and T-cell activation is unclear. We have examined the 6B2 expression
      on activated T cells and found that concanavalin A, anti-CD3 antibody and
      staphylococcal enterotoxin B (SEB) induced 6B2 expression on T cells. The
      expression was found on both CD4+ and CD8+ T cells and also was induced by SEB in
      vivo predominantly on CD8+ T cells. The 6B2+ T cells are IL-2R+ and blasted cells
      according to flow cytometry analysis. Therefore, the 6B2+ T cells are supposed to
      be in an activated stage. Enzymatic analysis demonstrated that trypsin treatment
      decreased the 6B2 expression, whereas neuraminidase increased the intensity on
      activated T cells. Neither endo-D or endo-H have any effect on the expression and
      there are no differences, in the results of immunoprecipitation and RT-PCR
      analysis, between control T cells and activated T cells. Taken together, the 6B2
      epitope is presumed to be the product of CD45R modification and is expressed on
      activated T cells. These results illustrate a novel classification of a T-cell
      subpopulation bearing a 6B2 epitope.

PMID- 7514809
TI  - Intrafamilial spread of hepatitis C virus infection.
AB  - We assessed the prevalence of antibodies to hepatitis C virus (anti-HCV) among
      401 household contacts of 161 persons with chronic hepatitis C (index patients).
      None of the index patients had antibodies against HIV. The overall prevalence of
      anti-HCV was 3.2% (2.5% in the absence of previous parenteral exposure). Sexual
      partners had a seroprevalence of 4.7% and non-sexual contacts, 2.5%. Among non
      sexual contacts, parents showed the highest rate (4.2%). The mean duration of
      exposure in the anti-HCV-positive sexual partners was 17.3 +/- 8.5 years, vis-a
      vis 9.2 +/- 7.4 years in the anti-HCV-negative sexual partners. We conclude that
      there is little risk of HCV infection through household contact. Although the
      form of transmission is not well identified, the duration of sexual activity
      suggests that the time needed to become infected is long.

PMID- 7514810
TI  - [Shoulder-arm pain in routine general practice].
AB  - The anatomical basis of shoulder-arm-pain syndromes is described. One has to
      practise a multidisciplinary approach in order to correctly analyse shoulder-arm
      pains. The most essential signs as well as the technique of examination of
      symptoms are described. The most frequent types of shoulder-arm-pain are
      subsequently mentioned.

PMID- 7514811
TI  - [Multiple sclerosis--what should be done?].
AB  - Major progress in MS-research has been achieved in recent years concerning
      diagnosis and differential diagnosis, pathogenetic mechanisms and prognostic
      indicators. Symptomatic treatment and prevention of complications help to improve
      quality of life and to prolong expected duration of life. Treatment trials
      intended to influence the course of the disease must still be considered
      experimental. Comprehensive rehabilitation remains the cornerstone of long-term
      management in MS. First results of carefully designed placebo-controlled double
      blind studies, however, justify the expectation, that more efficient measures to
      influence the course of the disease will be available in the near future.

PMID- 7514812
TI  - [Diagnosis bronchial carcinoma: therapeutic decisions].
AB  - Decisions about the best management of chest malignancies often are not black-and
      white decisions, but have to be taken in grey areas. In order to be aware of all
      treatment options and to appropriately weigh the profits and risks of treatment,
      the evaluation should be done by a teamwork of all specialists who can provide
      possible therapeutic benefit to the patient. In addition, it is a prerequisite
      that the informed patient and his primary care physician are fully involved in
      the collaborative treatment plan decided on.

PMID- 7514814
TI  - [Chemotherapy in lung carcinoma].
AB  - Lung cancer is still one of the main reasons for death in the western world. Its
      prevalence follows the pattern of smoking habits. Despite extensive research
      efforts there is still no break-through in systemic therapy of advanced lung
      cancer. Nevertheless, long-term survival has steadily been increasing during the
      last decades. This review is focussing on recent progress in treating non-small
      cell and small cell lung cancer patients.

PMID- 7514813
TI  - [Radiotherapy in malignant lung tumors].
AB  - Radiation therapy is performed in many different lung cancer situations, often in
      combination with chemotherapy and surgery. The indications for radiotherapy are
      limited disease in small cell lung cancer, postoperatively in not completely
      operated non-small cell lung cancer, medically inoperable lung cancer and not
      resectable locally advanced disease. Combined-modality approaches using various
      permutations of three treatment modalities, namely surgery, chemotherapy and
      radiotherapy, are currently under investigation. Palliative radiation therapy is
      able to reduce life-threatening symptoms from intrathoracic tumor as well as from
      distant metastases.

PMID- 7514815
TI  - [Special endobronchial palliative measures].
AB  - Inoperable pulmonary malignancies can present with local stenoses of the central
      airways either at the time of diagnosis or later on. Depending on their
      localization, these obstructions cause progressive dyspnea, postobstructive
      atelectasis and/or pneumonia. The patient's general condition will deteriorate,
      and at the tracheal level life-threatening dyspnea can develop. If central
      airways stenosis is suspected, fiberbronchoscopy is mandatory to decide whether
      local endobronchial palliation is a feasible treatment modality. Usually, local
      palliation is combined with chemo-and/or radiotherapy. Laser resection using the
      Nd-YAG laser is performed for obstructions caused by endoluminal tumour growth
      and leads to an immediate effect after a single session. Brachytherapy means
      local, endobronchial irradiation with a short depth of penetration. The active
      probe is placed with the aid of the fiberbronchoscope. Brachytherapy can be used
      alone, but is often combined with an initial laser resection for the
      consolidation of the treatment effect. The principal of photodynamic therapy
      consists of photosensitization of tumour cells followed by local laser light
      application which leads to cell death. In selected cases this treatment can be
      curative. Extrinsic stenoses which are caused by external compression of the
      airways or by thickening of the airway walls through submucosal tumour spread
      must be treated by dilatation and insertion of stents (endoprostheses) to
      maintain airway patency. These stents--mostly self-expanding silicone or metal
      devices--are usually inserted with the rigid bronchoscope. Again, endobronchial
      and/or percutaneous radiotherapy is added to obtain longer local tumour control.

PMID- 7514816
TI  - Increased activated protein C-protein C inhibitor complex levels in patients with
      pulmonary embolism.
AB  - Activated protein C (APC)-protein C inhibitor (PCI) complex level was examined in
      35 patients with acute pulmonary embolism (PE) and in 20 healthy volunteers.
      Thrombin-antithrombin III complex, plasmin alpha 2 plasmin inhibitor complex, and
      fibrin-D-dimer levels were significantly increased in the patients with PE
      compared to levels in healthy volunteers. Levels of plasminogen activator
      inhibitor-I, tissue type plasminogen activator, and von Willebrand factor
      antigens were also significantly increased in patients with PE. Plasma level of
      APC-PCI complex was increased in most patients with PE and APC-alpha 1
      antitrypsin complex level was increased in 13 patients. These complexes were not
      detected in healthy volunteers. These findings suggested that plasma protein C
      was activated in patients with PE, and that PCI was the major inhibitor of APC
      generated in this condition. Thus, regulation of the protein C pathway might play
      an important role in the pathogenesis of PE.

PMID- 7514818
TI  - An enzyme immunoassay of human polymorphonuclear leukocyte cathepsin G.
AB  - An enzyme immunoassay has been developed for the quantitation of human
      polymorphonuclear leukocyte cathepsin G. The assay had a linear relationship over
      the range 0.23-4.7 nmol/l (6-125 ug/l) and a detection limit of 0.23 nmol/l (6
      ug/l). Recovery in citrated plasma only occurred when the concentration was
      higher than 4.0 umol/l (110 mg/l). This effect could be overcome by diluting the
      plasma before adding the proteinase or by inactivating the proteinase before
      diluting it with plasma. The failure to detect cathepsin G in plasma was due to
      the plasma inhibitor alpha-2-macroglobulin masking the antigenic sites of the
      proteinase. Samples from several types of leukemia showed no detectable cathepsin
      G even when the total myeloid count was up to ten times the normal.

PMID- 7514817
TI  - Correlation between clotting and collagen metabolism markers in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis is a chronic inflammatory disease caused essentially by an
      immune-mediated mechanism. However, abnormalities of the clotting system have
      also been incriminated as having an important role in the pathogenesis of this
      disease. This study aims at assessing the clotting system and collagen metabolism
      alterations and the relationship between perturbances of the hemostatic pathway
      and the destructive and fibroproliferative processes in patients with rheumatoid
      arthritis. The coagulation system was evaluated by measuring thrombin
      antithrombin III complex (TAT), prothrombin time (PT), activated partial
      thromboplastin time (APTT), and antithrombin III (AT-III). The fibrinolysis
      system was assessed by measuring fibrin degradation products (FDP), fibrinogen
      (FBG), alpha 2-antiplasmin (alpha 2-PI), D-dimer (DD) and plasmin-alpha 2
      antiplasmin complex (PAP). As markers of collagen metabolism, the type III
      procollagen peptide (PIIIP) and the 7S domain of type IV collagen (7S-collagen)
      were determined. Blood concentrations of DD, PAP, TAT, PIIIP, and 7S-collagen
      were significantly higher in rheumatoid arthritis patients compared to controls.
      Serum levels of PIIIP were significantly correlated with PT, APTT, AT-III, FDP,
      and DD. 7S-collagen levels were inversely related to AT-III and FBG values. This
      study demonstrated the occurrence of a subclinical intravascular coagulation in
      rheumatoid arthritis and suggested the important role of blood coagulation in the
      alteration of the extracellular matrix metabolism in this disease.

PMID- 7514820
TI  - [Prostate-specific antigen and prostatic cancer].

PMID- 7514821
TI  - Kostmann's syndrome with chronic pneumonia and lymphocytosis: effect of
      recombinant human G-CSF.
AB  - Kostmann's syndrome is a congenital disorder characterized by impairment of
      myeloid differentiation in bone marrow with severe absolute neutropenia. A 17
      month-old girl was admitted to the hospital with complaints of recurrent skin
      infections since birth and severe pneumonia of the right lung which had been
      resistant to antibiotics since the patient was eight months old. Anemia, severe
      neutropenia and maturational arrest of granulocytes at the myelocyte stage in
      bone marrow were detected. At the age of 20 months, a right pneumonectomy was
      performed because of resistant cystic infection. Postoperatively, she was
      diagnosed with Kostmann's syndrome. Recombinant human granulocyte-colony
      stimulating factor (rhG-CSF) was administered intravenously at a dose of 3
      micrograms/kg/day, gradually increasing to 60 micrograms/kg/day in sequential
      seven-day courses to obtain a neutrophil count of more than 500 cells/mm3.
      Absolute neutrophil counts increased to greater than 1000 cells/mm3 at a dose of
      60 micrograms/kg/day, and at that time bone marrow aspiration revealed an
      increase in neutrophilic granulocytic precursors beyond the myelocyte stage. In
      order to maintain the neutrophil response, a dose of 20 micrograms/kg/day rhG-CSF
      subcutaneously was continued successfully. The patient has tolerated rhG-CSF
      treatment without complications, and infectious attacks have significantly
      decreased.

PMID- 7514819
TI  - Platelet aggregation inhibition by mononuclear leukocytes.
AB  - In this study we have investigated the effect of human mononuclear leukocytes
      (ML) on platelet aggregation. The results obtained demonstrated that coincubation
      of platelets with nonstimulated ML decreased platelet aggregation induced by
      collagen or thrombin in a concentration-dependent manner. The inhibitory effect
      increased with the incubation period of the cells, reaching a plateau at 5
      minutes. T and non-T enriched ML suspensions exerted an inhibitory effect similar
      to the total population of ML. Supernatants from ML or mixed cell suspensions
      also diminished platelet aggregation. 6-keto PGF1 alpha concentration in the
      supernatants was less than 10 pg/ml. Hemoglobin, L-arginine and cytochrome C did
      not modify the antiaggregating activity of ML, whereas superoxide dismutase
      potentiated the inhibition of aggregation mediated by ML. The inhibitory effect
      was not modified by monoclonal antibody (MoAb) against the lymphocyte function
      associated antigen 1, alpha subunit (LFA-1 alpha) or by a MoAb directed against P
      selectin. Our results demonstrated that ML inhibited platelet aggregation, at
      least partially, by the release of a soluble factor(s) distinct of prostacyclin
      or nitric oxide. Surface adhesion molecules seem also not to be involved.

PMID- 7514822
TI  - [The interrelationship between changes in the metabolic processes in the
      leukocytes and the concentration of mediators in the blood of eczema patients].
AB  - A study of histamine, serotonin, adrenaline and noradrenaline concentration in
      the blood and the content of DNA, RNA, glycogen and acid phosphatase revealed a
      relationship between the cellular immunity and neurohumoral changes in eczema
      patients. This enables to disclose in detail the mechanism of slow allergic
      reactions.

PMID- 7514824
TI  - Screening for prostate cancer.

PMID- 7514823
TI  - [The physicochemical anticomplement properties of alpha 2-macroglobulin for
      intravenous administration].
AB  - Stabilized composition of alpha-2-macroglobulin retains its physico-chemical and
      biological properties for 1 year storage at (6 +/- 2) degrees C. During this term
      it does not change its anticomplement activity, i.e. the alpha-2-macroglobulin
      concentrate with the stabilizer is safe for the body and ready for intravenous
      administration.

PMID- 7514825
TI  - Expression of the non-structural protein NS1 of bluetongue virus in bacteria and
      yeast: identification of two antigenic sites at the amino terminus.
AB  - cDNA transcribed from bluetongue virus serotype 1 (Australia) dsRNA 5 coding for
      non-structural protein NS1 was amplified in a polymerase chain reaction and
      ligated downstream of the T7 RNA polymerase promoter in the bacterial expression
      plasmid pET-5b, as a fusion protein with glutathione S-transferase using the pGEX
      bacterial expression system or the metallothionein promoter in the yeast
      expression plasmid pYELC5. The linear epitopes bound by six monoclonal antibodies
      to NS1 were localised to two antigenic regions at the amino terminus by Western
      blots using a series of carboxy-terminal truncations of the NS1 protein
      overexpressed in Escherichia coli. Expression of truncated NS1 genes using the
      pGEX expression system in E. coli enabled a more detailed map of the two epitopes
      to be constructed. The first epitope is thought to lie between amino acid
      residues 40-59, while the second is defined by the peptide sequences flanking
      amino acid 96.

PMID- 7514827
TI  - [Analysis of keratin filament structural transformation in human epithelial
      cells].
AB  - Upon 2-3 hours cold treatment (0 degrees C), the keratin filaments of some PcaSE
      1 cells and BEL-7404 cells are partly transformed into granular aggregates. But
      such structural transformation does not occur in HeLa cells and CNE cells. By
      rewarming (37 degrees C) cells within 15-30 minutes, this structural changes of
      keratin filaments in PcaSE-1 cells and BEL-7404 cells are readily reversed. In
      contrast, in HeLa cells and CNE cells, keratin filaments are transformed into
      granula aggregates during mitosis, but the keratin filament network in PcaSE-1
      cells and BEL-7404 cells remained intact and encircled the developing mitotic
      spindle as the cells entered mitosis. Results suggest that the above two types of
      keratin filament structural transformation might be induced by different factors.
      Our results also indicate that: (1) PcaSE-1 cells treated with colchicine alone
      or with combination of colchicine and cytochalasin D does not cause granular
      aggregates of keratin filaments. However, after depolymerization of microtubules
      with colchicine, the response of the cells to cold treatment is intensified. (2)
      The aggregate formation during cold treatment is unrelated to whether epithelial
      cells contain two different type intermediate filaments or not. (3) Epithelial
      cells preextracted with Triton X-100 do not induce granular aggregate formation
      of keratin filaments upon cold treatment. (4) The structural transformation upon
      cold treatment may be a characteristic of keratin filaments of certain epithelial
      cell lines.

PMID- 7514826
TI  - Trends in suicide mortality, 1955-1989: America, Africa, Asia and Oceania.

PMID- 7514829
TI  - Drugs recently released in Belgium. Eflornithine--finasteride.

PMID- 7514828
TI  - Orthodeoxia and platypnea in liver cirrhosis: effects of propranolol.
AB  - Chronic liver disease is well known to be associated with pulmonary
      abnormalities. Hypoxemia, clubbing, cyanosis and hyperventilation are common. The
      hypoxemia in cirrhotic patients has several causes: diffuse shunts due to
      intrapulmonary arteriolar vasodilatation, impaired hypoxic vasoconstriction,
      impaired matching of ventilation to perfusion, pleural effusions and
      diaphragmatic dysfunction. Because of gravity, shifting of blood to the dilated
      precapillary beds of the lung bases results in an increased hypoxemic dyspnea
      when the patient is in the upright position, also known as orthodeoxia and
      platypnea. It has only been described in 5% of the cirrhotic patients and has not
      been described in a Belgian refereed journal (Medline literature search 1983-Aug
      1993). It should be considered in the initial differential diagnosis of hypoxemia
      in patients with liver cirrhosis and dyspnea. Measuring arterial blood gases in
      the lying and upright position can prevent further invasive investigations, and
      whole body nuclide scan with technetium-99m macroaggregated albumin can confirm
      the diagnosis. Standard therapy with spironolactone (Aldactone) can worsen the
      condition and we found no additional benefit of beta-antagonists
      (propranolol/Inderal) in the reduction of the shunt fraction, probably because
      the main reason for the shunting is precapillary vasodilatation. Since there are
      no anatomical porto-pulmonary shunts, surgery is also inappropriate. The only
      therapy consists of oxygen supplements and low dose diuretics in patients with
      edema.

PMID- 7514830
TI  - Fine needle aspiration biopsy of hepatocellular carcinoma. Diagnostic dilemma at
      the ends of the spectrum.
AB  - A diagnostic dilemma exists at the extreme ends of the spectrum in the
      cytodiagnosis of hepatocellular carcinoma (HCC). The cytologic features of fine
      needle aspiration biopsies from 30 well- and 16 poorly differentiated HCC were
      reviewed and the adjunctive role of serum alpha-fetoprotein (AFP), hepatitis B
      virus (HBV) markers and radiologic findings evaluated. Some subtle features noted
      in very well differentiated HCC include small tumor cell size with increased
      nuclear/cytoplasmic ratio, monotony of atypia, hepatocytic tumor giant cells and
      narrow trabeculae with tendency for cell dissociation. Useful features in poorly
      differentiated HCC include cell dehiscence, large cells with ovoid nuclei and
      thickened nuclear membranes, and one or more increasingly prominent nucleoli,
      with some assuming a reniform configuration. The serum AFP levels are not always
      elevated. Positive HBV markers, cirrhosis and compatible imaging findings are
      suggestive but not diagnostic. The general inclination, however, is still toward
      a diagnosis of HCC if the aspirate is from a focal lesion or lesions in a
      hepatitis B surface antigen-positive, cirrhotic liver. Cell block sections
      provide histologic confirmation.

PMID- 7514831
TI  - Cytologic and differential diagnosis of rhinosporidiosis.
AB  - Rhinosporidiosis is a mycotic infection caused by Rhinosporidium seeberi. The
      fungus occurs in tissues as spherules measuring 0.25-3 mm. The spherules contain
      endospores. Diagnosis is usually made histologically on biopsy specimens from
      polypoid lesions on the mucous membranes of the nasopharynx, larynx, trachea,
      bronchus and conjunctiva. In our experience two cases of rhinosporidiosis were
      diagnosed by cytology. The cytologic features are typical. On direct examination
      the spherules are well-circumscribed, globular structures with several endospores
      within. The spherules show great variability in size, up to 10-fold. The diameter
      ranges from 30 to 300 microns. Permanent stains for detecting R seeberi are
      Giemsa, Gridley and toluidine blue. Numerous mycotic infections (Coccidioides
      immitis, Histoplasma capsulatum, Mucor, Aspergillus, Blastoschizomya capitatus,
      Paracoccidioides brasilienses, Cryptococcus neoformans) can be definitively
      diagnosed or strongly suspected on cytology. In immunocompromised patients it is
      important to commence the diagnostic study on unstained material. By direct
      examination R seeberi organisms are identified readily by their brown color. Much
      more information can be gained from material stained with special stains,
      especially periodic acid-Schiff, in differentiating R seeberi from Coccidioides
      immitis.

PMID- 7514832
TI  - Fine needle aspiration biopsy of hepatocellular carcinoma. Value of
      immunocytochemical and ultrastructural studies.
AB  - Over three years, 365 fine needle aspiration biopsies (FNABs) of the liver were
      performed at Ottawa Civic Hospital. Fifty-nine percent of these aspirates were
      positive for malignancy. A diagnosis of hepatocellular carcinoma (HCC) was made
      in 20 liver aspirates. The initial light microscopic diagnoses of HCC were
      confirmed by immunocytochemical and/or electron microscopic (EM) studies in 16
      aspirates. Canalicular pattern of staining with antibody to carcinoembryonic
      antigen (CEA), positive staining with anticytokeratin AE3 and negative staining
      with anticytokeratin AE1 supported the diagnosis of HCC. Although alpha
      fetoprotein (AFP) expression is relatively specific for HCC, it was positive in
      only 44% of cases, and the staining was usually focal. EM study confirmed the
      diagnosis of HCC in seven cases. Based on our findings and published reports, we
      use a diagnostic panel of antibodies to CEA, AFP and anticytokeratins AE1 and
      AE3, and/or EM study when there is a suggestion of HCC cytologically or
      clinically.

PMID- 7514834
TI  - Hepatoblastoma. Report of a case with cytologic, histologic and ultrastructural
      findings.
AB  - Hepatoblastoma, although rare, is the most common primary malignant neoplasm of
      the liver in children. In this paper we describe a case of hepatoblastoma with
      unusual cytologic features and present the histologic, immunocytochemical and
      ultrastructural features of this neoplasm. A 7-month-old girl presented with a
      large hepatic mass and metastatic nodules in both lungs. Intraoperative biopsy
      revealed a hepatoblastoma. Aspiration biopsy yielded a highly cellular aspirate
      with cords of pleomorphic cells embedded in a mucoid matrix. Histologic sections
      showed a diffusely infiltrative neoplasm composed of sheets and cords of highly
      pleomorphic cells. The neoplastic cells stained strongly positive for cytokeratin
      CAM 5.2 and AE1 and focally positive for alpha-fetoprotein, ferritin,
      carcinoembryonic antigen and vimentin. Ultrastructurally, the neoplastic cells
      had abundant intercellular junctions and intracytoplasmic aggregates of
      intermediate filaments. A mucoid matrix, to our knowledge, has not been reported
      as a finding on aspiration biopsy. This patient presented with pulmonary
      metastases, and thus we think the mucoid matrix may be a marker of a more
      aggressive variant of hepatoblastoma. This case illustrates additional cytologic
      features of hepatoblastoma and the usefulness of aspiration biopsy in the rapid
      diagnosis of this rare tumor.

PMID- 7514833
TI  - Primary diagnosis of disseminated coccidioidomycosis by fine needle aspiration of
      a neck mass. A case report.
AB  - Coccidioidomycosis is a pulmonary fungal infection endemic to the southwestern
      United States and northern Mexico. Disseminated coccidioidomycosis occurs in 0.1
      0.5% of cases and is a life-threatening condition. We report a case of
      disseminated coccidioidomycosis in an immunocompetent black male with cutaneous
      lesions, a flocculent neck mass, bilateral hilar adenopathy, persistent fever,
      night sweats and malaise. The clinical suspicion was lymphoma with cutaneous
      involvement. Fine needle aspiration (FNA) of the neck mass provided the primary
      diagnosis of coccidioidomycosis. It was confirmed by culture of FNA-obtained
      fluid and a subsequent biopsy of a cutaneous lesion. As shown in this case, FNA
      of soft tissue masses may provide rapid identification of the responsible
      organism and allow early initiation of therapy for this potentially life
      threatening infection.

PMID- 7514835
TI  - Aspiration cytodiagnosis of clear cell hepatocellular carcinoma in an elderly
      woman. A case report.
AB  - The cytohistologic features of a clear cell hepatocellular carcinoma are
      described. The case occurred in an elderly woman. An aspirate was obtained from a
      solitary mass in the right lobe of the liver. The liver carcinoma was found to be
      the clear cell type, with infrequent bile and hyaline (Mallory body-like) bodies
      in the cytoplasm. The fact that clear cell type hepatocellular carcinoma
      possesses specific cellular characteristics and immunocytochemical features
      renders this case report useful in establishing a correct cytohistologic
      diagnosis, especially since this tumor variant shows a striking resemblance to
      "clear cell" tumors that originate in other organs and that may cause a
      diagnostic dilemma.

PMID- 7514837
TI  - Diagnostic value of intranuclear vacuoles in benign breast disease.

PMID- 7514836
TI  - False-positive HMB-45 staining of axillary apocrine cells.

PMID- 7514838
TI  - The vestibular type I hair cells: a self-regulated system?
AB  - In this study the functional role of afferent nerve calyx surrounding the type I
      vestibular hair cells was investigated. Synaptic microvesicles were present at
      the apex of the calyx in the vestibular epithelium of human foetuses at 9 weeks
      from gestation. Whole cell clamped type I hair cells isolated from guinea pig
      epithelium presented active movements as shortening of the neck and tilting of
      the cuticular plate at the cessation of the depolarising step. These movements
      were calcium dependent. With the aim of establishing the kinetics of calcium
      influx during the cell depolarisation, intracellular free calcium rate variations
      were investigated by coupling cytofluorimetry technique with whole cell patch
      clamp. An increase of intracellular calcium was only observed at the
      repolarisation of type I hair cells. Thus, a regulatory short-loop is thought to
      exist to control adaptation phenomena at the upper part of the type I hair cell.
      It is suggested that this occurs through the release of a neurotransmitter from
      the apex of the afferent calyx.

PMID- 7514840
TI  - Decreased insulin-like growth factor binding protein-4 (IGFBP-4) mRNA levels in
      the liver after hypophysectomy.

PMID- 7514839
TI  - In vivo effects of local and systemic phencyclidine on the extracellular levels
      of catecholamines and transmitter amino acids in the dorsolateral striatum of
      anaesthetized rats.
AB  - The dose-dependent effects of systemically and locally administered phencyclidine
      (PCP) on the extracellular levels of dopamine, dihydroxyphenylacetate (DOPAC),
      homovanillate (HVA), 5-hydroxyindolacetate (5-HIAA), gamma-aminobutyrate (GABA),
      glutamate and aspartate in the dorsolateral striatum of anaesthetized rats were
      studied by in vivo microdialysis. Both local (1, 5, 50 and 100 microM) and
      systemic (2 and 10 mg kg-1 i.p.) PCP caused a dose-dependent increase in the
      extracellular levels of dopamine. The lowest PCP doses caused only a moderate but
      long-lasting increase in the extracellular levels of dopamine, while the highest
      PCP doses caused a massive but transient increase followed by a rebound decrease.
      The low doses of both systemic and local PCP tended to increase the levels of
      DOPAC, while those of HVA were not changed. The extracellular levels of 5-HIAA
      were increased only by the lowest (1 microM) locally administered dose of PCP.
      GABA levels were increased when PCP was administered locally at two doses. None
      of the treatments affected the extracellular levels of glutamate and aspartate.
      The results show that the effects of local and systemic PCP administration are
      dissimilar on the extracellular levels of 5-HIAA and GABA and thus provide new
      information on the neurochemical effects of PCP.

PMID- 7514841
TI  - Cloning and sequence analysis of bovine bone sialoprotein cDNA: conservation of
      acidic domains, tyrosine sulfation consensus repeats, and RGD cell attachment
      domain.
AB  - We isolated and sequenced a cDNA encoding bovine bone sialoprotein (BSP) using a
      bovine cDNA library made from mRNA isolated from bone-derived cell cultures and
      ligated to a phage lambda gt11. One of the cDNA clones isolated from this library
      had a 1800 base pair long insert and was found to contain the entire protein
      encoding region. The deduced protein sequence revealed a 310 amino acid protein
      containing a signal peptide sequence of 16 hydrophobic amino acids. The protein
      sequence shows remarkable conservation with previously published human and rat
      sequences (more than 80% similarity for both species). The potential functional
      domains of BSP, including three acid amino acid-rich sequences, tyrosine
      sulfation consensus repeats, and the RGD cell binding sequence, are all present
      in the bovine sequence. Northern analysis of RNA from different bovine tissues
      indicated the presence of BSP message in bone but not in other nonmineralized
      tissues, confirming that bone is the major site of BSP message production.

PMID- 7514842
TI  - [PSA in women. Evaluation of its determination with polyclonal and monoclonal
      immunoassay].
AB  - PSA concentrations were measured in 421 women. In a first group comprising 309
      subjects, the assay was carried out with kits containing polyclonal antibodies
      (PPSA). In the second group with 112 women, the assays used kits containing
      polyclonal antibodies (PPSA) and kits containing monoclonal antibodies (MPSA),
      and results obtained with both assays were compared. In the first group PSA
      levels higher than 0.4 ng/ml were detected in 47.9%. In the second group
      concentrations higher than 0.4 ng/ml were detected in 52.7% when using PPSA
      versus 16.7% when using MPSA. The rate of PSA detectable levels in healthy women,
      with benignant and malignant conditions was 36.7, 42.1 and 84.4% for PPSA, and
      16.7, 14.0 and 21.9 for MPSA. This study shows that it is possible to detect PSA
      levels in women, and that this is more frequent when using a polyclonal
      antibodies assay.

PMID- 7514843
TI  - [Clinical course in patients with BPH operated for acute urine retention].
AB  - Between 1980 and 1990, 5,949 cases of Benign Prostate Hyperplasia (BPH) were
      detected at the Puigvert Foundation. One thousand of them were randomized for
      analysis, and it was found that in 347 the indication for surgery was acute urine
      retention (AUR). During the initial visit the symptoms, their duration,
      creatinine values, correlation between creatinine and: 1) patients over 70 years,
      2) relationship to prostate size, 3) distention of the upper urinary tract, 4)
      vesical lithiasis, 5) urinary infection, 6) complications, and 7) mortality were
      analyzed. Discussion of results, comparing these to other series and trying to
      find evolution differences between these patients and those operated by elective
      surgery. In our series, we only found statistically significant differences when
      correlating the high values of creatinine with the prostate size and the upper
      urinary tract distension.

PMID- 7514844
TI  - [Mass screening for prostate cancer at a local town--five-year results and
      screening system].
AB  - The results of a mass screening examination for prostate cancer conducted from
      1989 to 1993 at a local town, Kawagoe-cho, in Mie Prefecture were evaluated.
      Among the 216 examinees, 4 were found to have prostate cancer. The most accurate
      examination was the prostate specific antigen (PSA), which was followed by
      digital examination and transrectal ultrasound. The applicants for the prostate
      cancer screening accounted for only 8% of the Kawagoe-cho male residents over 40
      years old. An educational campaign of prostate disease in the area must be
      started to increase the number of applicants. We concluded that the most
      effective modality for the screening program was a combination of PSA and digital
      examination in the field study, and transrectal ultrasound accompanied by
      systemic biopsy results in the second tool for screening.

PMID- 7514846
TI  - [A study of prostatic tissue levels of cefodizime (CDZM)].
AB  - Twenty-four patients suffering from prostate hyperplasia were given venous
      injections of CDZM of either 1 or 2 g at specific intervals (30 min, 1, 2 and 4
      hr) before surgery. Blood samples from the injected vein and tissue samples from
      the prostate were subsequently taken. In this study, the concentrations of CDZM
      in the prostate tissue (P) and in serum (S), as well as the ratio of the tissue
      to serum concentrations (P/S) were determined. In patients given 1 g injections,
      P ranged from 5.26-48.10 micrograms/g, while S ranged from 25.40-130.00
      micrograms/ml and P/S ranged from 12.6-37.0%. In the patients given 2 g
      injections, P ranged from 9.40-49.20 micrograms/g, S ranged from 62.30-234.00
      micrograms/ml and P/S ranged from 9.3-29.1%. CDZM exhibited excellent
      transmigration to the prostate tissue. Inflammatory bacteria present in
      prostatitis and urinary tract infections are generally those of E. coli, Proteus
      sp., but because the P range was much higher than the ratio of MIC, CDZM is
      expected to be useful against infections in the field of urology.

PMID- 7514845
TI  - [A case of nonseminomatous germ cell tumor: usefulness of alphafetoprotein
      subfraction].
AB  - Alfa-fetoprotein (AFP) is an indispensable examination in the management of non
      seminomatous germ cell tumor. However, many liver diseases also frequently show
      the elevation of AFP. Therefore, it is essential to discriminate between yolk sac
      derived component and liver-derived one. A 32-year-old male who had suffered from
      chronic hepatitis, visited our clinic in December, 1991. He complained of left
      scrotal atrophy and dull pain. Surgical specimen was histologically diagnosed as
      embryonal carcinoma with syncytiotrophoblastic giant cell. The levels of tumor
      markers, such as AFP, beta-human chorionic gonadotropin (beta-HCG), were
      estimated. Both of them were elevated, and radiographical studies demonstrated
      metastatic lesions of bilateral lung field and retroperitoneal lymph nodes
      (RPLN). After three courses of cisplatin based chemotherapy, lung and RPLN
      metastases diminished and serum beta-HCG had normalized. However, the serum AFP
      persisted to show an abnormally high concentration. The subfraction profile with
      lens culinaris hemagglutinin (LCA) was estimated. The one after the first course
      was compared with the one after third course. The latter one showed complete
      diminution of peak 2. This implied the diminishment of yolk sac element.

PMID- 7514847
TI  - The clinical relevance of L26, a B-cell-specific antibody, in Hodgkin's disease.
AB  - Although Reed-Sternberg cells and their variants (RS/V) in most cases of
      Hodgkin's disease (HD) lack lymphocyte-associated antigens, some cases of HD,
      particularly nodular lymphocyte-predominant HD (NLPHD), contain RS/V cells that
      appear to be of B-cell origin. This study was designed to test whether
      differences in clinical presentation and therapeutic response exist between
      patients with HD of various histologic types whose tumors contain RS/V cells that
      express antigens recognized by L26, an antibody directed against B lymphocytes,
      and those that do not. We studied 46 patients with stages I and II HD who were
      treated with radiotherapy alone between 1969 and 1986. Although the expression of
      L26 and the other antibodies was not predictive for relapse-free, cause-specific,
      or absolute survival, the labeling of the RS/V cells with L26, independent of
      histologic type, was significantly associated with peripheral lymph nodal
      presentation, male gender, and infradiaphragmatic presentation.

PMID- 7514849
TI  - Treatment of refractory severe aplastic anemia with granulocyte colony
      stimulating factor and interleukin 3.

PMID- 7514848
TI  - Differential expression of interleukin-2 receptors (alpha and beta chain) in
      mature lymphoid neoplasms.
AB  - We investigated the expression of interleukin-2 receptors (IL-2R) in 60 adult
      patients with mature lymphoid neoplasms by flow cytometric analysis, using two
      monoclonal antibodies, anti-Tac for IL-2R alpha-chain (IL-2R alpha) and Mik-beta
      1 for IL-2R beta-chain (IL-2R beta). Among B-cell malignancies, IL-2R alpha was
      found in 13/25 (52%) cases of chronic lymphocytic leukemia (CLL) and its
      variants, 3/14 (21%) of a heterogeneous group of non-Hodgkin's lymphoma (NHL) and
      none of the plasma cell diseases. IL-2R beta was not observed in any of B-cell
      neoplasms. IL-2R alpha was more frequently expressed in CD11b(+) B-cell neoplasms
      than in CD11b(-) (P < 0.05). In T-cell disorders, all three cases of adult T-cell
      leukemia/lymphoma expressed IL-2R alpha but not IL-2R beta. IL-2R beta was
      detected in 3/8 cases of CLL and 2/3 of NHL and none of these cases expressed IL
      2R alpha. CD8(+) malignant T-cells commonly displayed IL-2R beta. These data
      indicate that the IL-2R alpha and IL-2R beta in mature lymphoid neoplasms was
      expressed independently each other and was associated with the particular
      phenotypical characteristics of neoplastic cells, respectively.

PMID- 7514851
TI  - Invertebrate alpha 2-macroglobulin: structure-function and the ancient thiol
      ester bond.

PMID- 7514850
TI  - Effective treatment with dihydrostreptomycin of naturally infected cows shedding
      Leptospira interrogans serovar hardjo subtype hardjobovis.
AB  - The efficacy of dihydrostreptomycin in stopping the shedding of Leptospira hardjo
      subtype hardjobovis was studied in naturally infected cows. Blood and urine
      samples were collected from dairy cows kept on a farm where the farmer had
      contracted L hardjobovis infection. A microscopic agglutination test and an ELISA
      were used to determine specific antibody responses in serum. Polymerase chain
      reaction was used to detect bacterial shedding in urine. On the first sample
      collection date, 6 cows were seropositive, and 3 of those shed leptospires in the
      urine. These 3 cows were treated once with 25 mg of dihydrostreptomycin/kg of
      body weight. Within 1 week, the 3 cows stopped shedding leptospires. Six weeks
      later, 8 more lactating cows were found to be shedding leptospires. These cows
      were also treated once with dihydrostreptomycin, and they too stopped shedding
      leptospires within 1 week. From then on, the whole herd was examined weekly for a
      period of 2 months, and all cows Leptospira-positive by polymerase chain reaction
      were treated once with dihydrostreptomycin. Again, all cows stopped shedding
      leptospires in the urine within 1 week after treatment with dihydrostreptomycin.
      After a single treatment of the whole herd at the same time, new infections were
      not seen.

PMID- 7514852
TI  - Lectins from the colonial tunicate Clavelina picta are structurally related to
      acute-phase reactants from vertebrates.

PMID- 7514853
TI  - Computer-generated slide graphics on a shoestring budget.
AB  - The use of computer-generated slides in weekly didactic conferences and at
      regional and national meetings is commonplace. Though adding a professional look,
      the expense of computer-generated slides can be prohibitive. We herein present a
      simple technique for generating color slides that captures the professional look
      of computer-generated slides at a fraction of the cost.

PMID- 7514855
TI  - Identification of a mutation at codon 65 in the IKKK motif of reverse
      transcriptase that encodes human immunodeficiency virus resistance to 2',3'
      dideoxycytidine and 2',3'-dideoxy-3'-thiacytidine.
AB  - The technique of in vitro selection was used to generate variants of the human
      immunodeficiency virus type 1 that are resistant to 2',3'-dideoxycytidine (ddC).
      Most of the pol regions of such viruses, including the complete reverse
      transcriptase open reading frame and portions of flanking protease and integrase
      genes, were cloned and sequenced, using PCR-based procedures. Mutations were
      variously detected at amino acid site 65 (Lys-->Arg; AAA-->AGA) and at a
      previously reported codon, site 184 (Met-->Val; ATG-->GTG). We introduced the
      site 65 mutation into the pol gene of infectious, cloned HxB2-D DNA by site
      directed mutagenesis in order to confirm by viral replication assay the
      importance of this site in conferring resistance to ddC. The recombinant virus
      possessed greater than 10-fold resistance against this compound in comparison
      with parental HxB2-D. Cross-resistance of approximately 20- and 3-fold,
      respectively, was detectable against the (-) enantiomer of 2',3'-dideoxy-3'
      thiacytidine and 2',3'-dideoxyinosine but not against 3'-azido-3'-deoxythymidine.
      Combinations of the site 65 and 184 mutations did not yield levels of resistance
      higher than those attained with the site 65 mutation alone. The presence of the
      site 65 mutation was confirmed by PCR analysis of peripheral blood mononuclear
      cells from patients on long-term ddC therapy in 4 of 11 cases tested. Viruses
      that possessed a ddC resistance phenotype were isolated from subjects whose
      viruses contained the site 65 mutation in each of four instances. Four of these
      clinical samples were also demonstrated to possess the Met-184-->Val mutation,
      and one of them possessed both the Lys-65-->Arg and Met-184-->Val substitutions.
      Direct cloning and sequencing revealed the site 65 mutation in viruses isolated
      from these individuals.

PMID- 7514854
TI  - Antiviral drug resistance mutations in human immunodeficiency virus type 1
      reverse transcriptase occur in specific RNA structural regions.
AB  - A statistically significant correlation exists between the locations of drug
      resistance mutations (DRMs) observed for various reverse transcriptase inhibitors
      and features of the secondary structure predicted for the RNA coding for human
      immunodeficiency virus type 1 reverse transcriptase. The known DRMs map onto
      "unstable" bases, which are predominantly nonhelical regions (i.e., loops,
      bulges, and bends) of the predicted RNA secondary structure, whereas codons for
      the key conserved residues of polymerase sequence motifs map onto "stable" paired
      bases involved in helical regions. On the basis of these results, we hypothesize
      that the secondary structure of the RNA template (in this case, the reverse
      transcriptase gene itself) may be a previously unrecognized factor contributing
      to base misincorporation errors during reverse transcription and that, rather
      than being randomly distributed, mutations are more likely to occur in specific
      regions of the genome. The results suggest that these "mutation-prone" regions
      can be predicted by using a standard algorithm for RNA secondary structure.

PMID- 7514856
TI  - Resistance to 2',3'-dideoxycytidine conferred by a mutation in codon 65 of the
      human immunodeficiency virus type 1 reverse transcriptase.
AB  - A human immunodeficiency virus type 1 variant resistant to zalcitabine (2',3'
      dideoxycytidine [ddC]) was selected by sequential passage in the presence of
      increasing concentrations of ddC in peripheral blood mononuclear cell cultures. A
      mutation causing a lysine-to-arginine substitution was noted in reverse
      transcriptase (RT) codon 65 of this ddC-selected virus. A cloned mutant virus
      with this codon 65 mutation was constructed by using a novel PCR approach for
      site-directed mutagenesis. Characterization of this virus confirmed that the RT
      Lys-65-->Arg substitution was necessary and sufficient for a fourfold increase in
      the ddC 50% inhibitory concentration, as well as for resistance to didanosine
      (2',3'-dideoxyinosine [ddI]). Lys-65-->Arg and virus resistance to ddC and ddI
      also developed during therapy in isolates from one ddC-treated patient and two
      ddI-treated patients. Recombinant-expressed codon 65 mutant RT enzyme was
      resistant to ddCTP and ddATP in cell-free polymerase assays. Results of mutant
      enzyme studies are consistent with Lys-65-->Arg leading to changes in binding of
      the triphosphate forms of these nucleoside analogs to the RT. These data have
      implications for future studies of ddC resistance, particularly those aimed at
      defining its clinical relevance.

PMID- 7514861
TI  - [Inguinal hernia and prostatism].
AB  - Herein we describe the pathophysiological relationship between inguinal hernia
      and obstructive uropathy from prostatic hypertrophy, commonly known as
      "prostatism". We discuss the principles and the therapeutic approach when these
      conditions coexist, with special reference to combined surgery, whose main
      advantages are underscored.

PMID- 7514859
TI  - Expression of reverse transcriptase from feline immunodeficiency virus in
      Escherichia coli.
AB  - Reverse transcriptase from feline immunodeficiency virus (FIV) has been cloned
      and expressed in Escherichia coli. We have purified this recombinant enzyme and
      shown that it is a 66-kDa protein that is indistinguishable from virion-derived
      FIV reverse transcriptase in sensitivity to the 5'-triphosphates of 3'-azido-3'
      deoxythymidine and the four 2',3'-dideoxynucleosides. The availability of large
      quantities of the FIV reverse transcriptase will allow more detailed physical and
      pharmacological studies.

PMID- 7514857
TI  - Bisheteroarylpiperazine reverse transcriptase inhibitor in combination with 3'
      azido-3'-deoxythymidine or 2',3'-dideoxycytidine synergistically inhibits human
      immunodeficiency virus type 1 replication in vitro.
AB  - Bisheteroarylpiperazine compounds are nonnucleoside reverse transcriptase
      inhibitors of human immunodeficiency virus type 1 (HIV-1). To provide a rationale
      for combination therapy with a second-generation bisheteroarylpiperazine, we
      investigated the effect of U-90152 in combination with 3'-azido-3'-deoxythymidine
      (AZT) or 2',3'-dideoxycytidine (ddC). HIV-1-infected cells were cultured in the
      presence of test compounds, and drug effects on p24 core antigen production were
      measured by an enzyme-linked immunosorbent assay. In a CD4+ T-cell line (H9)
      infected with HIV-1IIIB, the 50% effective concentrations for U-90152, AZT, and
      ddC were 6.0, 80.4, and 31.8 nM, respectively. In human peripheral blood
      mononuclear cells infected with the molecularly cloned clinical isolate HIV
      1JRCSF, the 50% effective concentrations for U-90152, AZT, and ddC were 5.3, 5.9,
      and 25.0 nM, respectively. Over a range of drug concentrations (U-90152 and AZT
      at 0.3, 1, 3, 10, and 30 nM; ddC at 3, 10, 30, and 100 nM), U-90152 in
      combination with AZT or ddC synergistically inhibited the replication of a
      laboratory-adapted strain and a clinical isolate of HIV-1.

PMID- 7514860
TI  - Analysis of the penA gene of Pseudomonas cepacia 249.

PMID- 7514858
TI  - Combinative interactions of a human immunodeficiency virus (HIV) Tat antagonist
      with HIV reverse transcriptase inhibitors and an HIV protease inhibitor.
AB  - Combinations of the human immunodeficiency virus (HIV) Tat protein antagonist Ro
      24-7429 with either the HIV protease inhibitor Ro 31-8959 or the HIV reverse
      transcriptase inhibitors AZT (3'-azido-3'-deoxythymidine), ddC (2',3'
      dideoxycytidine), ddI (2',3'-dideoxyinosine), and nevirapine were synergistic or
      additive in reducing HIV type 1 p24 antigen production in CEM cells or inhibiting
      HIV type 1-induced syncytium formation in HT4-6C cells.

PMID- 7514862
TI  - Detection of Chlamydia trachomatis by direct fluorescent antibody staining.
      Results of the College of American Pathologists Proficiency Testing Program, 1986
      1992.
AB  - Since 1986 the College of American Pathologists has provided a proficiency
      testing program for laboratories that use the direct fluorescent antibody test
      for direct detection of Chlamydia trachomatis in clinical specimens. The number
      of survey participants increased from about 200 in 1986 to about 800 in 1992, and
      in all years the majority used reagents produced by Syva Co (Palo Alto, Calif),
      although the percentage decreased from 82% in 1986 to 68% in 1992. Performance on
      positive specimens varied based on specimen fixation method, number of elementary
      bodies present, serotype, and specific product used, and declined when the
      specimen was fixed with acetone prior to shipping or contained fewer than 50
      elementary bodies, particularly when the elementary bodies were of serotype L2.
      Performance with negative specimens was also variable, with 79% to 96% of all
      participants, and over 90% since 1991, responding correctly. In the last 1992
      survey, an ungraded specimen (a five-well slide containing latex beads
      incorporated with fluorescein isothiocyanate) and a questionnaire were included
      to assess the potential influence of laboratory operations on performance.
      Responses to the questionnaire and the ungraded specimen suggested that the level
      of experience of testing personnel affected performance. A test for trend in
      error rate across the number of years that a laboratory had offered the Chlamydia
      direct fluorescent antibody test indicated that error rate declined as degree of
      experience with the test increased.

PMID- 7514863
TI  - Transbronchial biopsy in patients with pulmonary eosinophilic granuloma.
      Comparison with findings on open lung biopsy.
AB  - We evaluated the findings on transbronchial biopsy specimens in reference to open
      lung biopsy specimens from 12 patients with pulmonary eosinophilic granuloma.
      Features in transbronchial biopsy specimens were further contrasted to those of
      patients with interstitial fibrosis and nondiagnostic biopsy specimens for
      localized lesions. Transbronchial biopsy specimens were randomized and graded for
      histologic features and cellularity. Patients with eosinophilic granuloma had
      more macrophages (P < .05) but equivalent numbers of eosinophils, neutrophils,
      and Langerhans' cells compared with those of the other two groups. Only two
      endoscopic biopsy specimens were histologically diagnostic or highly consistent
      with eosinophilic granuloma. We conclude that the diagnosis of eosinophilic
      granuloma is possible on transbronchial biopsy but requires a high index of
      suspicion. The demonstration of Langerhans' cells by immunohistochemical staining
      for S100 protein is a useful adjunct. The low diagnostic yield for eosinophilic
      granuloma on transbronchial biopsy results from inadequate sampling and from the
      nonspecific appearance of discrete lesions in small tissue samples.

PMID- 7514865
TI  - Lipoid proteinosis of the small bowel.
AB  - We describe a 65-year-old-man who presented with acute gastrointestinal bleeding
      secondary to massive submucosal deposits of hyaline material in the small bowel.
      The histochemical and ultrastructural features of the hyaline substance were
      typical of lipoid proteinosis, a rare cutaneous disorder in which, to our
      knowledge, symptomatic compromise of internal organs has not been described
      previously. The patient was later found to have mild but characteristic
      mucocutaneous lesions of lipoid proteinosis, as well as asymptomatic deposits in
      other gastrointestinal sites. Our case documents that severe visceral involvement
      may occur in lipoid proteinosis, even in previously undiagnosed patients with
      mild cutaneous manifestations of the disease.

PMID- 7514864
TI  - Carcinomas metastatic to follicular adenomas of the thyroid gland. Report of two
      cases.
AB  - Metastases to the thyroid gland are an uncommon occurrence, and metastasis to a
      preexisting thyroid neoplasm is even more rare. We report two cases of tumor-to
      tumor metastasis where a prostatic and a breast carcinoma metastasized to
      follicular adenoma of the thyroid gland. The metastatic process in case 1 was
      initially diagnosed by fine-needle aspiration biopsy and later confirmed with the
      hemithyroidectomy. Immunostaining for prostate-specific antigen and prostatic
      acid phosphatase in case 1 and estrogen and progesterone receptors in case 2
      demonstrated strong immunoreactivity in the metastatic tumor cells. Flow
      cytometric DNA analysis of the primary and the metastatic tumors in both cases
      demonstrated stemline fidelity that supported their association. Our cases
      exemplify why attention should be given to the possibility of metastasis when
      distinctly different morphologic features are seen in an otherwise typical tumor
      and the utility of ancillary tests that may assist in establishing the diagnosis.

PMID- 7514866
TI  - Immunoregulation of T cell-mediated skin hypersensitivity.
AB  - The recent extensive research on the different functions of T cells differing in
      cytokine production profiles has opened promising venues for further research on
      mechanisms and therapeutic options. Clearly, the routing hypothesis as described
      above still leaves many questions unanswered, such as the question why some
      chemicals may elicit strong Th2 responses and IgE antibody production even when
      applied to the skin, without apparent reduction of delayed allergic reactivity
      (Dearman et al., 1991). The preliminary understanding of regulatory mechanisms in
      allergic contact dermatitis has not yet led to further therapeutic progress. So
      far, no methods of permanent desensitization have been devised. Nevertheless,
      major cell types and mediators involved in allergic contact dermatitis have been
      identified. How T cells specifically recognize distinct allergens, and how these
      and other inflammatory cells interact to generate inflammation has begun to be
      understood. Moreover, the recently defined cellular interaction molecules and
      mediators provide promising targets for anti-inflammatory drugs. Obviously, drugs
      found to be effective in preventing severe T cell-mediated conditions, e.g.
      rejection of a vital organ graft, should be very safe before their use in
      allergic contact dermatitis would seem appropriate. To date, prudence favours any
      measure to prevent allergic contact dermatitis, be it through legal actions to
      outlaw the use of certain materials, or through avoiding personal contacts with
      these materials. In the meantime, for difficult-to-avoid allergens, further
      studies on the potential value of tolerogenic treatments should be intensified.

PMID- 7514867
TI  - Tyrosine phosphorylation of P-selectin in intact platelets and in a disulphide
      linked complex with immunoprecipitated pp60c-src.
AB  - P-selectin is a 140 kDa membrane glycoprotein found in secretory granules of
      platelets and endothelial cells where it is rapidly translocated to the plasma
      membrane upon cell activation. It then functions as a receptor for various types
      of leucocytes. Metabolic labelling of resting platelets with 32Pi showed that P
      selectin is primarily phosphorylated on serine residues, although some tyrosine
      phosphorylation was observed as well. However, tyrosine phosphorylation of P
      selectin was greatly stimulated by treatment with the permeating phosphatase
      inhibitor, pervanadate. When P-selectin immunoprecipitates were incubated with
      [gamma-32P]ATP (in vitro kinase assay), a fraction of P-selectin was
      phosphorylated on its tyrosine residues by a co-precipitated kinase. P-selectin
      phosphorylated in vitro co-migrated with 140 kDa surface-labelled 125I-P-selectin
      during SDS/PAGE under reducing conditions. Under non-reducing conditions,
      however, phosphorylated P-selectin was disulphide-linked to unknown protein(s) in
      a 205 kDa complex. In vitro kinase assays of the most abundant platelet tyrosine
      kinase, pp60c-src, demonstrated the presence of similar 140 and 205 kDa
      phosphorylated proteins in SDS/PAGE under reducing and non-reducing conditions
      respectively. Extraction and reprecipitation studies with proteins phosphorylated
      in vitro indicated that P-selectin and pp60c-src form a 205 kDa 1:1 disulphide
      linked complex. In the complex, pp60c-src autophosphorylation is inhibited and P
      selectin is phosphorylated on tyrosine residues. As protein disulphides in the
      cytoplasm of intact cells are extremely rare, our results suggest that P-selectin
      and pp60c-src, which co-localize in platelet dense granules, may be non
      covalently associated and spontaneously form disulphide bridges during lysis. In
      addition, the observed tyrosine phosphorylation of P-selectin in intact platelets
      suggests that its function might be regulated by phosphorylation by pp60c-src.

PMID- 7514868
TI  - Glucagon administration in vivo stimulates hepatic RNA and protein breakdown in
      fed and fasted rats.
AB  - Liver RNA and protein breakdown rates were measured simultaneously in fed and in
      24 h-fasted rats during a short-term cyclic perfusion, 1 h after an
      intraperitoneal injection of glucagon or of saline. RNA was labelled in vivo by
      an intraperitoneal injection of [6-14C]orotic acid, 60 h before the start of the
      perfusion. The accumulation of radioactive cytidine and valine in the perfusion
      medium for 15 min was used to determine RNA breakdown and proteolysis
      respectively. The portal glucagon/insulin ratio was significantly higher in the
      fasted glucagon-treated rats than in their fed counterparts. Although glucagon
      administration significantly increased RNA and protein degradation rates in the
      fasted and in the fed groups, the effect was greater after 24 h of starvation.
      The relationship between these biochemical changes and the alterations of the
      hepatocyte lysosomal system was investigated by determining the fractional
      cytoplasmic volume of lysosomal structures (autophagic vacuoles and dense bodies)
      by morphometry in the fasted glucagon-treated rats and in their controls.
      Hyperlucagonaemia significantly enhanced the relative volume of autophagic
      vacuoles without affecting that of dense bodies. The results showed that
      hyperglucagonaemia induced in vivo stimulated both liver RNA and protein
      breakdown and that this effect was modulated by the nutritional status of the
      rats.

PMID- 7514869
TI  - Interactions between neutral endopeptidase (EC 3.4.24.11) and the substance P
      (NK1) receptor expressed in mammalian cells.
AB  - Interactions between neutral endopeptidase-24.11 (NEP) and the substance P
      receptor (SPR; NK1) were investigated by examining substance P (SP) degradation,
      SP binding and SP-induced Ca2+ mobilization in epithelial cells transfected with
      cDNA encoding the rat SPR and rat NEP. Expression of NEP accelerated the
      degradation of SP by intact epithelial cells and by membrane preparations, and
      degradation was reduced by the NEP inhibitor thiorphan. In cells expressing SPR
      alone, specific 125I-SP binding after 20 min incubation at 37 degrees C was 92.2
      +/- 3.1% of maximal binding and was unaffected by thiorphan. Coexpression of NEP
      in the same cells as the SPR markedly reduced SP binding to 13.9 +/- 0.5% of
      maximal, and binding was increased to 82.7 +/- 2.4% of maximal with thiorphan.
      Coexpression of NEP in the same cells as the SPR also reduced to undetectable the
      increase in intracellular Ca2+ in response to low concentrations of SP (0.3 and
      0.5 nM), and significantly reduced the response to higher concentrations (1 and 3
      nM). The Ca2+ response was restored to control values by inhibition of NEP with
      thiorphan. In contrast, SP binding and SP-induced Ca2+ mobilization were only
      slightly reduced when cells expressing SPR alone were mixed with a 3- to 24-fold
      excess of cells expressing NEP alone. Therefore, in this system, NEP markedly
      down-regulates SP binding and SP-induced Ca2+ mobilization only when coexpressed
      in the same cells as the SPR.

PMID- 7514871
TI  - Conformation-dependent platelet adhesion to collagen involving integrin alpha 2
      beta 1-mediated and other mechanisms: multiple alpha 2 beta 1-recognition sites
      in collagen type I.
AB  - Platelet adhesion has been measured to type-I monomeric collagen, collagen
      fibres, alpha 1(I) and alpha 2(I) chains and the chain fragments alpha 1(I)CB3,
      alpha 1(I)CB6, alpha 1(I)CB7 and alpha 1(I)CB8, and alpha 2(I)CB3,5 and alpha
      2(I)CB4. Little if any adhesion occurred to any denatured species at 37 degrees
      C, demonstrating the importance of the collagen helix. However, on coating at 4
      degrees C to promote helix formation, and assaying at room temperature to avoid
      denaturation, adhesion was observed to both alpha-chain types and all fragments,
      the exact level of which depended on the identity of the species in question.
      Adhesion was strongly Mg(2+)-dependent. Antibodies against the integrin alpha 2
      beta 1 partially inhibited adhesion to alpha-chains and all fragments except
      alpha 1(I)CB6, indicating a wide distribution of alpha 2 beta 1-binding sites in
      the collagen molecule. 'Activation-dependent' adhesion to monomeric collagen,
      totally secondary to alpha 2 beta 1-mediated adhesion, involved at least two
      mechanisms, one mediated by integrin alpha IIb beta 3 and insensitive to
      prostaglandin E1, the other inhibitable by prostaglandin E1 but independent of
      integrin alpha IIb beta 3. alpha IIb beta 3-mediated adhesion to fragments was,
      at least in part, independent of the alpha 2 beta 1-mediated adhesion. Adhesion
      to fibres was largely bivalent-cation-independent with only minor involvement of
      integrin alpha 2 beta 1. Some alpha IIb beta 3-mediated adhesion occurred but was
      independent of any alpha 2 beta 1-initiated adhesion. Total 'activation
      dependent' adhesion to fibres was less than to monomeric collagen. Affinity
      chromatography revealed bivalent-cation-independent binding to fibres of three
      main platelet surface proteins, 90, 150 and 190 kDa in size.

PMID- 7514870
TI  - Reversibility of interleukin-1 beta-induced islet destruction and dysfunction by
      the inhibition of nitric oxide synthase.
AB  - We have examined the reversibility of NO-mediated islet dysfunction and
      destruction induced by interleukin-1 beta (IL-1 beta). Previous studies have
      shown that pretreatment of islets for 18 h with IL-1 beta results in an
      inhibition of glucose-stimulated insulin secretion that requires 4 days
      incubation in the absence of IL-1 beta to restore islet secretory function. In
      this study we use a sequential experimental design in which islets are first
      exposed to IL-1 beta for 18 h, and then treated with the NO synthase inhibitor NG
      monomethyl-L-arginine (NMMA). Insulin secretion is inhibited by 98% after the 18
      h incubation with IL-1 beta, and this inhibition is reversed in a time-dependent
      fashion by NMMA, with complete recovery of insulin secretion observed 8 h after
      the inhibition of NO synthase. Inhibition of NO synthase also restores IL-1 beta
      induced inhibition of mitochondrial aconitase activity in a time-dependent
      fashion that mimics the recovery of glucose-stimulated insulin secretion by
      islets. Ferrous iron and the reducing agents cysteine and thiosulphate accelerate
      the rate of recovery of insulin secretion, and ferrous iron and thiosulphate
      stimulate the recovery of islet aconitase activity, suggesting that iron
      sulphurcentre reconstitution may be involved in the recovery process. The
      recovery process also appears to require mRNA transcription, because the
      transcriptional inhibitor actinomycin D prevents the recovery of insulin
      secretion by islets after the inhibition of NO synthase. Although IL-1 beta
      induces the co-expression of NO synthase and cyclo-oxygenase by islets, cyclo
      oxygenase is not involved in the recovery of glucose-stimulated insulin
      secretion. Inhibition of NO synthase also prevents IL-1 beta-induced islet
      destruction, which otherwise occurs during a 96 h continuous exposure to this
      cytokine. The destructive effects of IL-1 beta on islet viability are prevented
      if NMMA is added to islet cultures during the first 24 h of exposure to IL-1
      beta, but islet destruction is not prevented if NMMA is added after the first 48
      h exposure to IL-1 beta. These results show that IL-1 beta-induced islet
      dysfunction is reversed by the inhibition of NO synthase, that recovery of
      insulin secretion is stimulated by iron and reducing agents, and that the
      recovery process appears to require mRNA transcription. We also show that it is
      possible to rescue islets from the destructive effects of IL-1 beta if NO
      synthase is inhibited early after its induction.

PMID- 7514873
TI  - Is it possible to predict the clinical effects of neuroleptics from animal data?
      Part V: From haloperidol and pipamperone to risperidone.
AB  - In 1965 the first study of this series reported different effects of neuroleptics
      in rats, supporting clinical differences. At the one end, haloperidol presented
      as a potent and specific antagonist of the psychostimulants amphetamine and
      apomorphine. Haloperidol-like neuroleptics have marked effects on psychomotor
      agitation, delusions and hallucinations and bind with high affinity to dopamine
      D2 receptors. Pipamperone, at the other end, presented with weak "dopamine"
      antagonism and more striking tryptamine antagonism. Pipamperone is known to
      improve disturbed sleep, social withdrawal and other symptoms of chronic
      schizophrenia in the relative absence of extrapyramidal symptoms. These effects
      have been attributed to central serotonin-S2 antagonism, on the basis of the
      clinical effects of ritanserin. As shown by the present analysis of relative
      tryptamine versus apomorphine antagonism of 57 neuroleptics, in comparison to
      relative S2 vs. D2 binding, there is a continuity in the series. About 30% of the
      compounds can be considered to act primarily as serotonin antagonists, but few
      are markedly more potent than pipamperone. In amphetamine-challenged rats
      pipamperone-like activity is reflected in preferential inhibition of the
      excessive oxygen consumption rather than of agitation. Risperidone inhibits
      oxygen consumption (0.016 mg/kg) at the same dose as haloperidol inhibits
      agitation. Other low-dose effects of risperidone include reversal of amphetamine
      induced withdrawal, antagonism of agitation induced by a sequential tryptamine
      and apomorphine challenge and LSD-antagonism. In dogs, the antiemetic activity of
      risperidone is characterized by high oral effectiveness which lasts one day and
      agrees with pharmacokinetic data when allowance is made for the active metabolite
      9-hydroxyrisperidone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514872
TI  - Immunocomplexes stimulate different signalling events to chemoattractants in the
      neutrophil and regulate L-selectin and beta 2-integrin expression differently.
AB  - Neutrophils express receptors for numerous phlogistons which, when occupied,
      trigger distinct signal-transduction pathways. Previous studies have shown that
      stimulation of neutrophils with chemoattractants induces shedding of the adhesive
      molecule L-selectin and increased expression of the beta 2-integrin CD11b/CD18.
      We determined the effect of ligation of classic, G-protein-linked chemoattractant
      receptors [C5a, interleukin-8 (IL-8), formylmethionyl-leucylphenylalanine (FMLP)
      and substance P], receptors for the Fc portion of IgG (Fc gamma receptors) and
      receptors for transforming growth factor beta (TGF beta) on expression of
      adhesive molecules by neutrophils and the stimulus-transduction mechanisms
      thought to mediate these changes. We were surprised to observe that occupancy of
      Fc gamma receptors by immunocomplexes (BSA-anti-BSA) stimulated increased
      expression by neutrophils of CD11b/CD18 at concentrations which did not affect L
      selectin expression (EC50 9 micrograms/ml versus 350 micrograms/ml respectively,
      P < 0.00001, n = 5). In contrast, similar to previous studies, recombinant C5a,
      recombinant IL-8 and FMLP all stimulated increased expression of CD11b/CD18 (170
      260% of basal, P < 0.001, n = 5) and shedding of L-selectin (56-75% reduction
      from basal, P < 0.001, n = 5) at similar concentrations and with similar
      potencies (EC50 = 2, 5, and 3 nM respectively). In contrast, neither TGF beta 1
      nor, surprisingly, substance P affected expression of CD11b/CD18 or L-selectin.
      The regulation of expression of CD11b/CD18 or L-selectin in response to FMLP or
      immunocomplexes was unaffected by cytochalasin B (5 micrograms/ml) or the
      tyrosine kinase inhibitor tyrphostin-25 (25 microM). Although occupancy of both
      chemoattractant (FMLP) and Fc gamma receptors stimulated increments in the second
      messenger diacylglycerol, disruption of actin microfilaments by cytochalasin B
      enhanced diacylglycerol generation in response to FMLP but not in response to
      ligation of Fc gamma receptors. Moreover, both FMLP and immune aggregates
      provoked fluxes of intracellular Ca2+ concentration which differed with respect
      to both magnitude and kinetics and did not correlate well with regulation of
      adhesive-molecule expression. As upregulation of CD11b/CD18 is tightly linked to
      exocytosis of specific granules, these results suggest that shedding of L
      selectin by activated neutrophils is not linked to exocytosis. These studies
      provide further evidence that receptors for chemoattractants and immunocomplexes
      on the neutrophil are linked to multiple signalling pathways.

PMID- 7514874
TI  - Effect of 1-year treatment with nitrendipine versus enalapril on urinary albumin
      and alpha 1-microglobulin excretion in microalbuminuric patients with type 1
      diabetes mellitus. A randomized, single-blind comparative study.
AB  - In order to compare the long-term effects of nitrendipine (CAS 39562-70-4) and
      enalapril (CAS 75847-73-3) on variables of glomerular and tubular function in
      type 1 diabetes mellitus, a single-blind, randomised comparative 1-year study was
      carried out in microalbuminuric patients (6 women, 14 men, age, 30-58 years,
      duration of diabetes, 3-41 years, HbA1 sigma 5.5-10%). 10 patients were treated
      with 20 mg/d nitrendipine, 10 patients were treated with 10 mg/d enalapril. On
      the average, urinary albumin excretion was decreased by 38 +/- 4% by nitrendipine
      (p < 0.01 vs. before treatment) and by 21 +/- 8% by enalapril (p < 0.05 vs.
      before treatment). The excretion of alpha 1-microglobulin decreased by 35 +/- 10%
      and by 39 +/- 9%, respectively (p < 0.05 vs. before treatment). Creatine
      clearance rose by 20 +/- 30% during nitrendipine treatment (p < 0.05 vs. before
      treatment) but was unchanged during enalapril treatment. Total kidney volume
      decreased by 23 +/- 4% (p < 0.01) and by 14 +/- 6% (p < 0.05), respectively.
      Blood pressure fell by 8 +/- 1% systolic and by 13 +/- 1% (diastolic) in
      nitrendipine-treated patients (both p < 0.01) and by 10 +/- 1% and 13 +/- 1% in
      enalapril-treated patients (both p < 0.01). Thus, nitrendipine long-term
      treatment of microalbuminuric type 1 diabetic appeared to be as effective as the
      treatment with enalapril in preventing or postponing the progression of diabetic
      nephropathy.

PMID- 7514876
TI  - Reduction of the severity of bronchial hyperresponsiveness by the novel
      leukotriene antagonist 4-oxo-8-[4-(4-phenyl-butoxy)benzoylamino]-2- (tetrazol-5
      yl)-4H-1-benzopyran hemihydrate.
AB  - There is much evidence that the cysteinyl-leukotrienes (C-LTs) are important in
      the pathogenesis of asthma. The clinical effect of a new leukotriene antagonist,
      ONO 1078 (4-oxo-8-[4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4H- 1
      benzopyran hemihydrate, CAS 103177-37-3) on symptoms, pulmonary lung function and
      bronchial hyperresponsiveness was evaluated in patients with bronchial asthma.
      Eleven patients were treated for 24 weeks with 450 mg of ONO 1078 twice daily.
      The score of asthma symptom severity and the number of inhaled procaterol were
      significantly reduced after 2 weeks of ONO 1078 treatment and remained decreased
      for another 22 weeks. Their FEV1 and PC20 to histamine significantly improved 12
      and 24 weeks after ONO 1078 treatment. The effectiveness of ONO 1078 suggests
      that the C-LTs play an important role in the pathogenesis of asthma. ONO 1078
      might help to favorably modify the pathophysiologic condition in patients with
      bronchial asthma.

PMID- 7514875
TI  - Influence of theophylline on both bronchoconstriction and plasma extravasation
      induced by acetaldehyde in guinea-pigs.
AB  - Acetaldehyde administered intravenously at various doses (20, 40 and 80 mg/kg)
      elicits a dose-dependent increase in intratracheal pressure (ITP) and a
      proportional rise in histamine blood concentration in anaesthetized guinea-pigs.
      Similar effects were observed in ovalbumin-sensitized guinea-pigs upon aerosol of
      acetaldehyde (20 mg/ml) which has been administered at the flow rate of 0.1
      ml/min for 2 min. Theophylline (CAS 58-55-9) antagonized both the increase of ITP
      values and the rise of histamine in the blood caused by acetaldehyde given
      intravenously (ED50 = 5.8 mg/kg i.v.) or by aerosol (ED50 = 4.9 mg/kg i.v.).
      Furthermore, in animals where combined treatment with pyrilamine (2 mg/kg i.v.)
      and captopril (2 mg/kg i.v.) resulted in a remarkable potentiation of the
      bronchoconstrictor response to acetaldehyde (20 mg/kg i.v.), the administration
      of theophylline (5 mg/kg i.v.) or of the substance P (SP) receptor antagonist, [D
      Pro4, D-Trp7.9] SP 4-11 (10 mg/kg i.v.) reduced the augmented action of
      acetaldehyde on respiratory airways induced by captopril by more than 50%.
      Moreover, the bronchoconstriction induced by acetaldehyde (40 mg/kg i.v.) was
      also associated with a significant increase of extravasation of Evans blue in
      tracheal tissue. Both these effects of acetaldehyde were inhibited by
      theophylline (10 mg/kg i.v.), whereas a NK1-TK (neurokinin 1-tachykinin) receptor
      antagonist (412 micrograms/kg i.v.) reduced (81%; p < 0.001) only the vascular
      permeability changes caused by acetaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514877
TI  - Effects of antiallergic agents including levocabastine on experimental rhinitis
      in rats.
AB  - Topical application of levocabastine hydrochloride (-)-[3S-[1(cis)-3 alpha,4
      beta]]-1-[4-cyano-4-(4-fluorophenyl) cyclohexyl]-3-methyl-4-phenyl-4
      piperidinecarboxylic acid monohydrochloride, inhibited the increase in dye
      leakage into the nasal cavity induced not only by antigen in actively sensitized
      rats but also by histamine in non-sensitized rats. The potency of levocabastine
      was stronger than that of ketotifen in inhibiting the increase of dye leakage in
      both cases. In addition, levocabastine as well as ketotifen exerted a more potent
      inhibition of the dye leakage induced by histamine than that induced by antigen.
      Levocabastine also exerted a significant inhibition on the dye leakage induced by
      substance P; again the effect of levocabastine was more potent than that of
      ketotifen. On the other hand, levocabastine elicited no remarkable influence on
      the dye leakage induced by either acetylcholine or platelet activating factor.
      However, ipratropium and (RS)-2-methoxy-3-(octadecylcarbamoyloxy)propyl 2-(3
      thiazolio)ethyl phosphate were effective when the corresponding agonists were
      perfused, respectively.

PMID- 7514878
TI  - Monoamine activity in anterior hypothalamus of guinea pig pups separated from
      their mothers.
AB  - Brief isolation in a novel environment increased the ratios of 3-methoxy-4
      hydroxyphenylethylene glycol to norepinephrine (MHPG:NE) and
      dihydroxyphenylacetic acid to dopamine (DOPAC:DA) in the anterior hypothalamus of
      guinea pig pups. Ratios were significantly elevated after 90 min of isolation and
      for MHPG:NE, after 30 min of isolation; changes were due to increases in MHPG and
      DOPAC. Home cage isolation produced no change in any measure of catecholamine
      activity. No changes in levels of serotonin or its metabolite were observed. In 1
      experiment, resting levels of NE and DOPAC:DA were predictive of the rate of
      separation-induced vocalization. Maternal separation in the context of novelty
      increases hypothalamic NE and DA activity; however, both isolation and novelty
      are required because neither maternal separation in the home cage nor exposure to
      a novel cage together with the mother had any discernible effect.

PMID- 7514880
TI  - Gene expression of a thermostable beta-galactosidase in mammalian cells and its
      application in assays of eukaryotic promoter activity.
AB  - The gene (lacS) encoding a thermostable beta-galactosidase enzyme (Ss beta-gal)
      from the archaebacterium Sulfolobus solfataricus has been cloned and expressed in
      simian CV1 and murine NIH3T3 cell lines. The recombinant protein is an active
      enzyme that shows the same properties of thermophilicity and thermostability as
      the wild-type Ss beta-gal and has no cytotoxic effect on the host cells. Its
      possible use as a reporter gene is also proposed, and a comparison with other
      reporter gene systems is made.

PMID- 7514879
TI  - Engineering of the human-immunodeficiency-virus-type-1 (HIV-1) reverse
      transcriptase gene to prevent dimerization of the expressed chimaeric protein:
      purification and characterization of a monomeric HIV-1 reverse transcriptase.
AB  - We report here a human-immunodeficiency-virus-type-1 (HIV-1) recombinant reverse
      transcriptase (RT) engineered to contain a 26-amino-acid linker insertion from
      the tether domain of feline leukaemia virus (FLV) RT. The chimaeric protein was
      expressed in Escherichia coli and migrated on SDS/PAGE as a 68 kDa band. A
      monomeric form of the chimaeric HIV-1 RT has been prepared by the coordinated
      applications of immobilized-metal-affinity chromatography and gel filtration on
      Superose 12 columns. The monomeric nature of this chimaeric HIV-I RT was further
      characterized by cross-linking studies using disuccinimidyl suberate. The RNA
      dependent DNA polymerase activity of the monomeric chimaeric HIV-1 RT was 35%
      that of the heterodimeric (p66/p51) HIV-1 RT. These results support our recent
      studies on the monomeric polymerase domain (p51 RT) which exhibited an RNA
      dependent DNA polymerase activity equal to 33% of that of the p66/p51
      heterodimeric HIV-1 RT (Evans, Kezdy, Tarpley and Sharma [1993] Biotechnol. Appl.
      Biochem. 17, 91-102). The inability of the monomeric chimaeric HIV-1 RT to
      display polymerase activity like that of the heterodimeric HIV-1 RT is attributed
      to a decrease in the processive rate of DNA synthesis (75%) and DNA binding
      (65%). However, the monomeric chimaeric HIV-1 RT (p68) exhibited RNAase H
      activity like that of the heterodimeric form (p66/p51) of HIV-1 RT. These results
      suggest that the linker insertion from FLV RT does not interfere with the RNAase
      H activity associated with the monomeric HIV-1 RT.

PMID- 7514881
TI  - A site-directed antibody recognizes a component of the ouabain-binding domain of
      the alpha 1 subunit of rat Na+,K(+)-ATPase.
AB  - Antibodies (AbE1) were raised against an oligopeptide derived from a component of
      the ouabain-binding site of the alpha 1 subunit of rat Na+,K(+)-ATPase.
      Preincubation of partially purified Na+,K(+)-ATPase from rat kidney with 1 microM
      AbE1 partially inhibited the enzyme and reduced its sensitivity to 1 mM ouabain.
      Antibodies against an unrelated protein were ineffectual. Unexpectedly, the
      masses of the proteins detected on immunoblots of rat kidney by AbE1, a 160
      kilodalton (kDa) doublet, was greater than the 97 kDa of the alpha 1 subunit. In
      lysates prepared with hot (85 degrees C) buffer constituted according to
      Laemmli's formulation for sample buffer (buffer L, a low chaotropic buffer), AbE1
      always bound to the 160-kDa doublet. In contrast, AbE1 did not bind any proteins
      on blots of lysates that were prepared with buffer that contained greater
      concentrations of detergent and reducing agent (Laemmli's "homogenization"
      buffer, buffer H, a high chaotropic buffer), regardless of temperature. However,
      the presence of alpha 1 in lysates produced in homogenization buffer was
      confirmed by the presence of 97-kDa bands that were detected with two additional
      site-directed antibodies that recognize the alpha 1 subunit. When homogenates
      prepared with sample buffer L were examined, one of these antibodies bound to
      bands of 160 kDa, indicating that alpha 1 is a component of the bands bound by
      AbE1. It is concluded that AbE1 recognizes a component of the ouabain-binding
      site of Na+,K(+)-ATPase, but only under conditions in which the alpha 1 subunit
      was associated into a higher molecular mass complex.

PMID- 7514885
TI  - [Histological analysis of craniopharyngiomas--with special reference to their
      histological origin and differentiation].
AB  - The histogenesis of craniopharyngiomas was immunohistochemically studied on the
      basis of cytokeratins (CK) expression, with special reference to histological
      subtype, i.e., the squamous type (Sq) and adamantinomatous type (Ad). Alcian-Blue
      staining and immunohistochemical expression of secretory component were also
      studied to assess secretory activity. Although combined expression of simple-,
      stratified-, and skin-type CK was detected in both Sq and Ad, the pattern of
      expression in Sq and Ad was different. Sq displayed epidermal differentiation of
      CK, and secretory activity was limited to the apical cells of Sq. Based on these
      findings, the histogenesis of Sq appeared to be from Rathke's pouch, but that of
      Ad remained obscure.

PMID- 7514883
TI  - Structure of the lipopolysaccharide O-antigen of Pseudomonas cepacia serotype A.
AB  - The O-antigenic polysaccharides of the lipopolysaccharides produced by three
      isolates of Pseudomonas cepacia serogroup A were analysed by composition,
      methylation, periodate oxidation, and two-dimensional nuclear magnetic resonance
      methods. They were found to be identical linear unbranched polymers of a
      repeating trisaccharide unit containing 2-acetamido-2-deoxy-D-galactose and L
      rhamnose residues (2:1) and have the structure [-->3)-alpha-D-GalpNAc-(1-->3)
      beta-D-GalpNAc-(1-->4)-alpha-L-Rhap -(1-->]n.

PMID- 7514884
TI  - Ecocultural assessment in families of children with developmental delays:
      construct and concurrent validities.
AB  - Home interviews were conducted with 102 families of children with developmental
      delays to assess ecocultural family resources and constraints, values, and goals
      as well as proactive adaptive efforts to deal with their circumstances. Interview
      topics included (a) economic factors; (b) child safety, health, and education;
      (c) domestic and childcare workloads; (d) familial support networks; and (e)
      sociocultural influences. Factor analyses performed on the ecocultural measures
      revealed 12 salient factors. Results indicated that some of the ecocultural
      factors were unique and statistically independent of the traditional measures of
      home environment (e.g., child-rearing attitudes, cognitive stimulation of the
      child, and general psychosocial climate). Significant relations were found
      between certain ecocultural factors and child's developmental status. Both
      ecocultural factors and traditional family measures accounted for significant
      variation in child outcomes.

PMID- 7514886
TI  - You make the diagnosis: case study. Postoperative respiratory status of a 76-year
      old man.

PMID- 7514882
TI  - MAP kinases from bovine brain: purification and characterization.
AB  - We have purified 42- and 44-kilodalton (kDa) isoforms of the mitogen-activated
      protein (MAP) kinase family from bovine brain. The kinases were assayed with
      myelin basic protein as the substrate and detected by anti-sea star p44mpk
      antibody. Purification was achieved using phenyl-Sepharose, polylysine-agarose,
      hydroxylapatite, and Mono-Q column chromatography. Both myelin basic protein and
      smooth muscle caldesmon, but not histone H1, served as good substrates. Based on
      chromatographic behaviors and specific activities toward myelin basic protein, it
      is likely that the 42-kDa brain isoform is similar to that of brain tau kinase.
      The 44-kDa enzyme, however, is a novel brain MAP kinase isoform not reported
      previously. Although it has been demonstrated that p44mpk can be activated in
      vitro through phosphorylation by the tyrosine kinase p56lck, neither of the brain
      kinases were significantly stimulated by the tyrosine kinases p56lck, p56lyn, or
      p59fyn. However, based on antibody cross-reactivity, a MAP kinase kinase is
      present in the crude brain extract. Both brain MAP kinases were capable of
      autophosphorylation which occurred, at least in part, on tyrosine residues.
      However, only the 44-kDa isoform showed a significant degree of coincident
      activation.

PMID- 7514888
TI  - Differential expression of transforming growth factor-alpha (TGF-alpha) and EGF
      receptor in transitional area of psoriatic epidermis.
AB  - We investigated the localization of TGF-alpha and EGF receptor in psoriatic
      plaques, especially the clinically-determined transitional zone from uninvolved
      to involved psoriatic skin by immunohistochemistry. TGF-alpha was not increased
      in the transitional area compared with normal epidermis. It started to increase
      within the edge of psoriatic plaques. In contrast, EGF receptor increased up to
      the suprabasal layers even in the uninvolved skin adjacent to psoriatic plaques,
      compared with normal epidermis. Slight epidermal hyperplasia was also observed in
      the clinically-determined transitional area. This result suggests that the
      increase of EGF receptor precedes that of TGF-alpha in psoriatic plaque
      formation.

PMID- 7514889
TI  - mRNA binding track in the human 80S ribosome for mRNA analogues randomly
      substituted with 4-thiouridine residues.
AB  - The interaction between mRNA and 18S rRNA in human 80S ribosomes has been studied
      using synthetic mRNA analogues randomly substituted with 4-thiouridine, which can
      be photoactivated for cross-linking. Two mRNA analogues with different sequences
      have been used for complex formation with ribosomes without or with the presence
      of a cognate tRNA. Cross-linked 18S rRNA nucleotides were identified by reverse
      transcription analysis. The base U630 in 18S rRNA was the main target of cross
      linking for both of the mRNA analogues studied, and three minor sites of cross
      linking, A1060, U1046, and U966, were also identified. Thus, in the case of human
      80S ribosomes, the set of nucleotide residues cross-linked to the mRNA analogues
      is significantly smaller than the twelve sites seen for Escherichia coli with
      these same two mRNA analogues [Bhangu, R., & Wollenzien, P. (1992) Biochemistry
      31, 5937-5944]. The residue U630 is within a highly conserved region
      corresponding to the 530 loop region of eubacterial 16S rRNA; the cross-link to
      this site indicates that it plays a key role in interacting with mRNA on 80S
      ribosomes independently of the presence of a cognate tRNA at the P site.

PMID- 7514887
TI  - Neuropsychological correlates of central monoamine function in chronic
      schizophrenia: relationship between CSF metabolites and cognitive function.
AB  - Schizophrenia is associated with multiple cognitive deficits which in turn may be
      related to abnormal dopamine (DA) function. To examine possible associations
      between cognitive dysfunction and central DA activity in schizophrenia,
      neuropsychological measures (visuospatial and verbal recall; performance on the
      Wisconsin Card Sort Test (WCST); visuospatial perception) were examined in 17
      drug-free male schizophrenic patients and related to cerebrospinal fluid
      concentrations of the metabolites of dopamine (homovanillic acid (HVA)),
      serotonin, and norepinephrine. CSF HVA concentrations were correlated with the
      ability to recall visuospatial information, with attention to verbal tasks, and
      with WCST performance (low CSF HVA concentrations predicting poor performance on
      these tests) but not with the ability to recall verbally presented material and
      visuospatial perception. These data are consistent with earlier results
      suggesting that (cortical) DA function is associated with recall and retrieval of
      visuospatial information and with WCST performance.

PMID- 7514890
TI  - Molecular cloning of the canine CD44 antigen cDNA.
AB  - Molecular cloning of the dog homologue of the human CD44 was achieved using
      RT/PCR. A 1055 bp cDNA has a deduced amino acid sequence of 351 residues, 338 of
      them correspond to the mature protein. Nine conserved cysteine residues were
      found. The extracellular region contains a single link superfamily domain on the
      N-terminal part and potential post-translational modification sites as: N- and O
      linked glycosylation sites and chondroitin sulfate attachment sites. Three mRNAs
      of 2.2, 3.8 and 4.4 kb were identified on Northern blot analysis and Western blot
      hybridization revealed a 85-90 kDa protein expressed in lymph node tissue.

PMID- 7514891
TI  - Aphidicolin-resistant Chinese hamster ovary cells possess altered DNA polymerases
      of the alpha-family.
AB  - DNA polymerases alpha, delta and epsilon were partially purified and
      characterized from a wild type Chinese hamster ovary (CHO) cell line and from two
      aphidicolin-resistant mutant CHO cell lines (BR5 and BR5-20a). The main
      characteristics of the wild type and mutant DNA polymerases were compared in
      order to reveal differences in the properties of these enzymes responsible for
      the aphidicolin resistance of the mutant cell lines. Pol alpha's of the mutant
      cells show: (1) in vitro aphidicolin-resistance, (2) 1.5-3-fold lower specific
      activity than that of the wild type, (3) resistance to cytosine and adenosine
      arabinofuranoside 5'-triphosphate (araCTP and araATP), (4) altered resistance to
      carbonyldiphosphonate (COMDP) and to alkylphenyl nucleotide analogs (butylphenyl
      dGTP and butylanilino-dATP), and (5) lower activity on poly(dA)/oligo(dT)
      template-primers. These changes in the biochemical properties of this enzyme may
      result from a mutation in pol alpha gene. Pol epsilon and delta of the mutant
      cells did not differ from the wild type enzymes with respect to aphidicolin
      resistance. However, the specific activities of these mutant enzymes were much
      higher (1.5 to 8-fold for pol epsilon and 4 to 20-fold for pol delta) in
      comparison to that of the wild type enzymes. Also in comparison to the wild type
      enzymes, the mutant pol epsilon showed changes in the template-primer preference;
      whereas the mutant pol delta was found to have altered sensitivity to other
      inhibitors. These results indicate that pol epsilon and pol delta are also
      altered as a secondary effect of mutation in the aphidicolin-resistant cells. It
      is suggested that these altered properties of the DNA pols of the alpha family
      are responsible for the in vivo aphidicolin resistance of the mutant cells.

PMID- 7514892
TI  - Dideoxy sequencing and structural analysis of the rat insulin-like growth factor
      binding protein-1 gene.
AB  - Insulin-like growth factor binding protein-1 (IGFBP-1) is an important modulator
      of IGF bioavailability. To facilitate studies of IGFBP-1 regulation and function
      in rodent models, we cloned the rat IGFBP-1 gene and analyzed its structure by
      dideoxy sequencing. The rat IGFBP-1 gene is relatively small (approximately 5 kb)
      and contains 4 exons and 3 introns, similar to the human IGFBP-1 gene.

PMID- 7514893
TI  - [Stabilization of a conducting channel in lipid bilayer membranes by an electric
      field].
AB  - A strong transversal electric field is shown to stabilize a macroscopic
      conducting pore in a lipid membrane. The dependence of the pore radius on the
      applied voltage is obtained.

PMID- 7514894
TI  - Bleomycin differentially inhibits picornavirus, herpesvirus and poxvirus
      replication in a human carcinoma cell line.
AB  - MS-757, a cervix carcinoma cell line, was exposed to bleomycin at concentrations
      up to 200 microM for periods of 1 to 24 hours. Bleomycin treatment caused the
      level of DNA synthesis in uninfected cells to drop to 13% of the level achieved
      in the controls. Protein synthesis fell to 50%, but RNA synthesis was not
      affected. Exposure of uninfected cells to 200 microM bleomycin for 24 h did not
      induce significant cell death measured as permeability to Trypan Blue). A
      tetrazolium dye-reduction assay, however, showed that cell viability measured as
      mitochondrial activity was reduced by 50%. In contrast, the clonogenicity of the
      treated cells (measured as colony-forming ability) fell to less than 1% of the
      level in untreated controls. Bleomycin effected a highly selective inhibition of
      virus replication measured as production of infectious progeny virus. The
      replication of the RNA virus, coxsackievirus B5, was largely unaffected by
      bleomycin, whereas the replication of the DNA virus, herpes simplex virus type 2,
      was inhibited to the same extent as cellular DNA synthesis. In contrast,
      bleomycin caused a 2 to 3 log10-fold suppression of the production of progeny
      virus after infection with the DNA virus, vaccinia virus. When an early gene
      product (expressed prior to virus DNA replication) of vaccinia virus was assayed,
      little inhibitory effect of bleomycin could be demonstrated, indicating that the
      early transcription and translation of vaccinia virus was only modestly
      influenced by bleomycin. The results argue against a DNA-based replication as the
      bleomycin-susceptible function independent of genome, replication enzymes, and
      site of synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514895
TI  - Evaluation of integrated morpho-biological indicators in breast cancer.
AB  - A series of 71 patients undergoing surgery for primary breast carcinoma was
      prospectively studied in order to verify the relationships between clinical and
      pathological variables, proliferative indexes and DNA-ploidy. Significant
      correlations between proliferative indexes were found; conversely, DNA-ploidy
      showed no correlation with either PCNA/cyclin or AgNORs, but only with flow
      cytometry S-phase fraction (FCM-S) and IF-vimentin. In the 42 patients with a
      mean follow-up of 42 months, disease-free rate was best predicted by nuclear
      grade (p < 0.001), histological grade (p < 0.001), mitoses (p 0.001), IF-vimentin
      (p 0.002), FCM-S (p 0.002), PCNA (p 0.005) and Ag-NORs (p 0.007).

PMID- 7514896
TI  - Human B cell immune response to selected epitopes of the polymorphic epithelial
      mucin (PEM) in cancer patients.
AB  - Human antibodies were generated by Epstein-Barr Virus (EBV) immortalization of B
      cells derived from tumor draining lymph nodes of cancer patients. Antibodies were
      screened for reactivity in ELISA against a synthetic peptide corresponding to the
      protein core of the Polymorphic Epithelial Mucin (PEM). Epitopes within this
      region are in fact considered to be tumor specific since they are selectively
      exposed on tumor cells due to aberrant glycosylation. Human antibodies thus
      selected react in ELISA and immunohistochemistry with PEM-expressing tumor cells.
      This is the first demonstration of the existence of B cell immune response
      against selected epitopes of PEM and, in association with the cytotoxic T cell
      (CTL) response already demonstrated, represents the basis for the use of
      synthetic peptides as vaccines in cancer patients.

PMID- 7514898
TI  - [Effect of a constant magnetic field on the rate of growth and angiogenesis in
      endothelial cells in vitro].

PMID- 7514897
TI  - [Effect of morphine on RNA synthesis in various structures of the rat brain with
      varying narcologic resistance].

PMID- 7514900
TI  - Transforming growth factor-beta regulates c-kit message stability and cell
      surface protein expression in hematopoietic progenitors.
AB  - The cell-surface receptor c-kit and its cognate ligand stem-cell factor (SCF) or
      steel factor (SLF) are important for the maintenance of hematopoiesis both in
      vitro and in vivo. Transforming growth factor-beta (TGF-beta) has been shown to
      be a potent inhibitor of SLF-mediated synergistic growth of murine Lin-Sca-1+
      progenitor cells, as well as more committed progenitors. In the present study, we
      examined the regulation of c-kit mRNA and cell-surface expression by TGF-beta.
      Among the murine hematopoietic progenitor cells tested, the myeloid cell line FDC
      P1 and the mast-cell line MC-6, as well as progenitor-enriched bone marrow cells,
      constitutively expressed functional cell-surface c-kit. Treatment of these
      progenitor cell lines and primary progenitor cells with TGF-beta resulted in
      downregulation of cell-surface c-kit expression. This effect was not a secondary
      event of cell-cycle status. TGF-beta inhibition was dose- and time-dependent,
      with 50% inhibition seen between 0.3 to 3 ng/mL TGF-beta and maximal inhibition
      at 30 ng/mL. Using the FDC-P1 cell line, we observed that the inhibition of cell
      surface c-kit expression by TGF-beta is preceded by a marked reduction in c-kit
      mRNA levels starting 2 hours after TGF-beta treatment, and reaches a maximum by 6
      hours. The inhibition in steady-state c-kit mRNA levels is explained, in part, by
      a decrease in the half-life of c-kit transcripts (2 to 4 hours for control cells
      v 0.5 to 1.5 hours for TGF-beta-treated cells). These findings suggest that TGF
      beta regulates the responsiveness of murine hematopoietic progenitors to SLF
      through a decrease in c-kit message stability leading to decreased cell-surface
      expression.

PMID- 7514901
TI  - Splenic primitive hematopoietic stem cell (PHSC) activity is enhanced by steel
      factor because of PHSC proliferation.
AB  - To test whether primitive hematopoietic stem cells (PHSCs) are stimulated by
      Steel (SI) factor (c-kit ligand) in vivo, donor mice were studied after three or
      seven daily injections of SI factor. PHSC activity was measured as long-term
      erythroid and lymphoid competitive repopulating ability. Cells to be tested
      (usually marrow or spleen cells from treated donors) were mixed with untreated
      competitor marrow that produces erythrocytes and lymphocytes that are genetically
      distinguishable from the donors by differences in hemoglobin (Hb) and
      glucosephosphate isomerase (GPI) markers. These cell mixtures were injected into
      lethally irradiated hosts, and after 111 to 293 days, functional abilities of
      donor PHSC populations were assessed and expressed as percentages of donor-type
      Hb and GPI in the host's circulating erythrocytes and lymphocytes, respectively.
      A striking increase in splenic PHSC activity occurred after seven daily
      injections of SI factor, with a much smaller increase after three daily
      injections. Both three and seven daily injections of SI factor slightly reduced
      marrow PHSC activity. Rapid cycling greatly increases PHSC vulnerability to 5
      fluorouracil (5FU). To test whether SI factor stimulates PHSCs into rapid
      cycling, donor mice were given a dose of 5FU in addition to SI factor. The
      increase in splenic PHSCs after 7 days of treatment with SI factor occurred to a
      similar degree whether donors were or were not treated with 5FU on day 8.
      However, a dose of 5FU on day 4 of the SI factor treatments almost totally
      prevented the increase in splenic PHSC activity. Apparently this increased
      activity requires PHSC cycling throughout the period of SI factor treatment.

PMID- 7514899
TI  - [Determination of NO-synthase activity in the brain (new method)].

PMID- 7514902
TI  - Bifunctional effects of tumor necrosis factor alpha (TNF alpha) on the growth of
      mature and primitive human hematopoietic progenitor cells: involvement of p55 and
      p75 TNF receptors.
AB  - Tumor necrosis factor alpha (TNF alpha) has previously been reported to have both
      inhibitory and stimulatory effects on hematopoietic progenitor cells.
      Specifically, TNF alpha has been proposed to stimulate early hematopoiesis in
      humans. In the present study we show that TNF alpha, in a dose-dependent fashion,
      can potently inhibit the growth of primitive high proliferative potential colony
      forming cells (HPP-CFCs) stimulated by multiple cytokine combinations. Using
      agonistic antibodies to the p55 and p75 TNF receptors or TNF alpha mutants
      specific for either of the two TNF receptors, we show that both receptors can
      mediate this inhibition. In contrast, the potent stimulation of interleukin-3 (IL
      3) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) induced HPP-CFC
      colony formation observed at low concentrations of TNF alpha (2 ng/mL) was only a
      p55-mediated event. Moreover, the stimulatory effects of TNF alpha on GM-CSF or
      IL-3-induced colony formation, as well as the inhibition of G-CSF-induced colony
      growth, were also exclusively signaled through the p55 TNF receptor. Taken
      together, our results suggest that the inhibitory effects of TNF alpha on
      primitive bone marrow progenitor cells are mediated through both p55 and p75 TNF
      receptors, whereas the p55 receptor exclusively mediates the bidirectional
      effects on more mature, single factor-responsive bone marrow progenitor cells as
      well as stimulation of IL-3 plus GM-CSF-induced HPP-CFC colony growth.

PMID- 7514904
TI  - Perturbations in the fibrinolytic pathway abolish cyst formation but not
      capillary-like organization of cultured murine endothelial cells.
AB  - Fibrinolytic activity and its relation to morphogenesis was investigated in
      several transformed murine endothelial cell lines and primary cultures of
      endothelial cells. Two in vitro systems, fibrin gels and Matrigel (Collaborative
      Research, Bedford, MA), were used. Fibrin gels model a fibrin-rich extracellular
      matrix that frequently supports neovascularization in vivo, and Matrigel models
      the basement membrane surrounding quiescent endothelial cells in vivo. The
      transformed endothelial cell lines have higher levels of plasminogen activator
      (PA) mRNA than primary cultures of endothelial cells, and an increased PA
      mediated proteolytic activity was correlated with formation of cysts in fibrin
      gels. Addition of neutralizing anti-urokinase antibodies, plasminogen depletion,
      or addition of a plasmin inhibitor prevented cyst formation. Addition of
      plasminogen restored the ability to form cysts in the plasminogen-depleted
      system. Normal endothelial cells organized into capillary-like structures in
      fibrin gels regardless of manipulations affecting the fibrinolytic pathway. In
      Matrigel, both transformed and primary cultures of endothelial cells rapidly
      formed a capillary-like network that was not affected by plasminogen depletion or
      addition of plasmin inhibitors. Thus, elements of the fibrinolytic pathway
      necessary for cyst formation are not critical in capillary-like structure
      formation on a reconstituted basement membrane. These results suggest that
      plasmin is essential for hemangioma formation but is not critical to the
      organizational behavior of normal endothelial cells.

PMID- 7514906
TI  - Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil
      aggregation.
AB  - Human neutrophils are primed in the presence of complexes of lipopolysaccharide
      (LPS) with its serum binding protein (LBP) in a manner dependent on CD14.
      Cellular consequences of priming include increased responsiveness, the
      upregulation of surface proteins including the adhesive integrin CD11b/CD18 (Mac
      1), the increased binding of certain ligands to CD11b/CD18, and the concurrent
      shedding of the L-selectin homing receptor. Because expression of both CD11b/CD18
      and L-selectin is obligatory for formyl peptide-stimulated neutrophil aggregation
      in vitro (Simon et al, Blood 82:1097, 1993), we have examined the consequences of
      bacterial endotoxin on the expression of neutrophil adhesive molecules. We
      observed that the exposure of neutrophils to LPS/LBP, while enhancing the surface
      numbers and adhesive function of CD11b/CD18 for latex particles, did not induce
      aggregation. In contrast, as the LPS/LBP concentration increased (ED50 = 30 ng/mL
      LPS/LBP), the ability of neutrophils to aggregate decreased in parallel with the
      shedding of L-selectin. Moreover, when L-selectin adhesive activity was blocked
      by treatment with Fab fragments of Dreg-200, aggregation was inhibited to an
      extent roughly proportional to the available L-selection. Blocking of LPS/LBP
      with CD14-specific monoclonal antibodies suppressed L-selectin shedding and
      preserved formyl peptide-stimulated aggregation. Taken together, the data suggest
      that inhibition of neutrophil aggregation by LPS/LBP is related to the expression
      of L-selectin via CD14 rather than LPS inhibition of CD11b/CD18 function during
      cellular stimulation.

PMID- 7514903
TI  - Expression of CD33, CD38, and HLA-DR on CD34+ human fetal liver progenitors with
      a high proliferative potential.
AB  - High proliferative-potential colony-forming cells (HPP-CFC) have been identified
      in the bone marrow of mice and adult humans, and have been characterized as a
      compartment of primitive progenitors possibly including stem cells. In this
      report we describe the human fetal liver (FL) as a source of HPP-CFC. These FL
      HPP-CFC develop in clonal cultures in the presence of granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) within 3 to 4 weeks.
      The median frequency of HPP-CFC in FL tissues between 16 and 21 weeks of
      gestational age was 1 in 3,000 total FL cells. After 4 weeks of growth, FL HPP
      CFC grew to a median colony size of 8.3 x 10(4) cells/colony. Using cell-sorting
      techniques FL HPP-CFC were shown to be predominantly contained in the CD34+ CD33+
      CD38- fraction of FL cells. FL HPP-CFC were heterogeneous for HLA-DR expression,
      and no differences in proliferative capacities were observed between HLA-DR+ and
      HLA-DR- HPP-CFC. The CD34+ CD33-HLA-DR- CD38- population, previously suggested to
      contain stem cells, was observed to be very rare in the FL, representing
      approximately 1 in 1.7 x 10(5) light-density FL cells and containing almost no
      CFC. Therefore, it is possible that stem cells are contained in the CD33+
      fraction of FL cells. Phenotypic characterization of CD34+ CD33+ CD38- lin -LDFL
      cells showed that these cells are also CD13+, predominantly Thy-1+, CD45RA-,
      CD45RO-, CD71-, and heterogenoeous for c-kit expression. These data suggest that
      FL HPP-CFC represent a heterogeneous compartment of primitive myeloid progenitors
      that may include stem cells.

PMID- 7514907
TI  - The -158 (C-->T) promoter mutation is responsible for the increased transcription
      of the 3' gamma gene in the Atlanta type of hereditary persistence of fetal
      hemoglobin.
AB  - The Atlanta type of hereditary persistence of fetal hemoglobin (HPFH) is
      characterized by a mild elevation of Hb F (2% to 5% in heterozygotes), almost
      exclusively of the G gamma type (more than 90%). Gene-mapping analysis has
      identified this condition as a -G gamma-G gamma- arrangement with the -158 (C-
      >T) substitution in the promoters of both G gamma genes. We have reevaluated this
      condition in members of two families. Sequence analysis identified only two
      changes in the 3' gamma gene as compared with the A gamma gene from a chromosome
      with haplotype no. 3 (or Senegal), namely the -158 (C-->T) promoter mutation and
      the C-->G change in codon (CD) 136, which accounts for the -G gamma-G gamma-
      phenotype. The absence of any other nucleotide (nt) substitution provides genetic
      evidence that the -158 (C-->T) change is primarily responsible for the elevated
      Hb F levels associated with this condition. A quantitative reverse
      transcription/polymerase chain reaction (RT/PCR) procedure, presented in detail
      in this report, was developed to determine the effect of this mutation on the
      transcription of individual gamma genes in four individuals with the Atlanta type
      of HPFH. Both gamma-globin genes, ie, the (5') G gamma and the (3') G gamma
      Atlanta genes of the Atlanta type of HPFH chromosome, expressed elevated amounts
      of transcripts, which were present in nearly equal amounts. This shows that the 
      158 (C-->T) mutation exerts its effect on the transcriptional rate of the gene
      with which it is associated.

PMID- 7514905
TI  - Establishment and characterization of cloned human thymic epithelial cell lines.
      Analysis of adhesion molecule expression and cytokine production.
AB  - The thymic stromal microenvironment is required for the generation of
      immunocompetent T lymphocytes. However, the different thymic stromal cell types
      have not been fully characterized and their roles regarding T-cell development
      are not completely understood. To address the phenotypic characteristics of the
      epithelial component of the human thymic microenvironment as well as its
      functional involvement in T-cell development, we have established cloned thymic
      epithelial cell (TEC) lines from fetal and postnatal human thymuses by an explant
      technique, repeated subculture, and limiting dilution cloning. These cloned TEC
      lines were shown to be derived from cortical epithelium and to express a number
      of cell-surface molecules including CD40, major histocompatibility complex (MHC)
      HLA-ABC and HLA-DR antigens, homing-associated cell-adhesion molecule (H-CAM),
      intercellular adhesion molecule-1 (ICAM-1), leukocyte function-associated antigen
      3 (LFA-3), and beta 1 subfamily integrins. Finally, both postnatal and fetal TEC
      clones were shown to produce interleukin-1 alpha (IL-1 alpha), IL-6, and IL-7.
      These well-defined cloned TEC lines may provide useful tools for the study of TEC
      biology and for the understanding of the precise role played by TEC in human T
      cell development.

PMID- 7514908
TI  - Acute infections in atopic dermatitis: a clue for a pathogenic role of a Th1/Th2
      imbalance?
AB  - Temporary improvement of atopic dermatitis lesions may occur after acute, severe
      infections. One such case is shortly described, and it is then proposed that such
      a phenomenon may serve as an indirect evidence to support the finding of a
      predominant Th2 imbalance in atopic dermatitis.

PMID- 7514910
TI  - Primary rhabdoid tumour of the skin in a 14-month-old child.
AB  - We report on a primary cutaneous rhabdoid tumour in a 14-month-old child, to the
      best of our knowledge, the second case in the literature. The tumour showed a
      multipolypoid gross appearance and classical histological features. The
      neoplastic cells were positive for keratin and vimentin and most were positive
      for proliferating cell nuclear antigen. The ultrastructural examination revealed
      typical intracytoplasmic aggregates of intermediate filaments. The tumour showed
      a very aggressive course, and the child died 5 months after the diagnosis of
      cerebral metastasis.

PMID- 7514909
TI  - Localization of perforin in viral vesicles and erythema multiforme.
AB  - BACKGROUND: Perforin (Pf), a pore-forming protein, is a cytolytic protein of
      killer cells. Its deposition in lesioned skin has not been studied. OBJECTIVE:
      The purpose of this study is to show Pf deposition in the lesioned skin and Pf
      expression in the dermal infiltrates of various inflammatory skin diseases.
      METHODS: Frozen specimens obtained from 29 patients with 5 different diseases
      were immunohistochemically stained. RESULTS: Granular deposition of Pf was found
      in the lesioned skin in 2 out of 5 cases of viral vesicles and in 3 out of 7
      cases of erythema multiforme. In the cases with Pf deposition, the percentages of
      Pf+ cells in the dermis were higher than in those without deposition. CONCLUSION:
      Pf released from natural killer cells or cytotoxic T lymphocytes may play a role
      in tissue damage.

PMID- 7514911
TI  - Comment: cost in treating malignant pleural effusions with bleomycin.

PMID- 7514912
TI  - Outcome again.

PMID- 7514913
TI  - Prediction of pain center treatment outcome for geriatric chronic pain patients.
AB  - OBJECTIVE: Geriatric chronic pain patients (age 65 and over) form an increasing
      percentage of the pain center treatment population. It is therefore important to
      be able to predict pain center treatment success or failure for these patients;
      this is the first study to address this concern. DESIGN: Chronic pain patients
      rated themselves at pain center admission and discharge on 43 rating scales for
      the areas of pain, functional status, behavioral variables, and other pain center
      modification categories. The 43 scores at admission were used as potential
      predictors, while the 43 change scores (from admission to discharge) were the
      outcome measures to be predicted. Additional possible predictors were 16 other
      variables that are considered prognostic of treatment outcome, including age,
      number of surgeries, and prior occupational level. The statistical analysis
      consisted of a five-step procedure: (a) mathematical techniques were used to
      remove redundant outcome measures; (b) each of the remaining outcome variables
      was correlated with the full set of predictor variables; (c) regression
      techniques were used to predict the outcome variables; (d) these outcome
      variables were combined into independent factors using factor analysis; and (e)
      regression techniques were used to predict the factors. RESULTS: The variable
      reduction technique was successful in removing 26 of the 43 outcome variables.
      Factor analysis of change scores of the remaining variables resulted in four
      factors, which were identified as change in activity, change in pain and
      behavior, change in constant pain, and change in attitude to pain center goals.
      The analysis showed that the best predictor of a variable's change score was the
      initial level of that variable. Regression analysis, using all variables as
      predictors except initial level, found a number of statistically significant
      predictors. However, no predictor variable, alone or in combination, was able to
      account for > 30% of the variance of any outcome measure. CONCLUSION: These
      results indicate that we cannot as yet predict geriatric pain center treatment
      outcome. Potential reasons for these results are discussed.

PMID- 7514914
TI  - Clinical evaluation of pain treatment with electrostimulation: a study on TENS in
      patients with different pain syndromes.
AB  - OBJECTIVE: We evaluated the clinical efficacy and the unwanted side effects of
      transcutaneous electrical nerve stimulation (TENS) in a consecutive group of
      patients with intractable pain due to different pain syndromes. METHODS: Two
      hundred eleven patients with different pain syndromes, coded according to the
      International Association for the Study of Pain (IASP), were treated with TENS,
      using a standardized protocol. After a 6-month treatment period, an independent
      investigator estimated the effect of TENS in retrospect through assessment of
      patient files, standardized questionnaires, and diaries. In addition, a physical
      examination to determine the IASP code was performed, and unwanted side effects
      were evaluated. RESULTS: TENS showed a favorable response in the majority of
      patients with pain caused by peripheral nerve damage (53%), anginal pain
      resulting from ischemic heart disease (75%), and pain of the musculoskeletal
      system due to mechanical degenerative causes (69%). TENS employed in patients
      with prominent psychological and social distress, and for pain caused by central
      and autonomic dysfunction, alleviated pain in only 10-25% of the patients. Side
      effects occurred in 35% during the initial period of the treatment and were
      usually able to be resolved, especially with thorough supporting instructions
      during the initial treatment period. CONCLUSIONS: In this study, the beneficial
      effect of TENS appeared to be related to the etiology of the underlying pain. The
      effect of TENS was maintained for > 6 months in the majority of patients with an
      immediate favorable response. Supporting instructions are crucial for long-term
      success.

PMID- 7514915
TI  - Developmental screening at four years of age. Relation to home situation,
      perinatal stress, development and behaviour.
AB  - A developmental screening programme constructed for the use of Swedish child
      welfare centres on four-year-old children has been tested on a cohort of 471
      children who have been followed up from the stage of early pregnancy. The results
      of the screening test were compared with data in the project using a
      multidisciplinary, longitudinal and prospective design. The test, which can be
      performed by a child welfare centre nurse and which is not time-consuming,
      includes four items summed up in a four-years-of-age score: the child is asked to
      name three easily recognizable objects, to draw a cross (according to a model),
      and to draw a man; in addition, an evaluation is made of speech development. On
      average, boys were found to have a lower score than girls. The results of the
      screening test were related to data available in the ongoing project; to the
      psychosocial conditions of the families, to foetal and perinatal factors (reduced
      optimality score according to Prechtl), to the presence of psychopathology, and
      to the results of Griffiths' developmental scales. The developmental screening
      score, which in most instances was associated with the Griffiths' scales, was
      found to be related to psychosocial problems in the family and to abnormal
      behaviour and psychiatric symptoms in the child, but not to reduced optimality
      scores. The results indicate that a relatively simple screening method is of
      value for the identification of children who are at risk of abnormal mental and
      behavioural development, and who may thus be in need of special care and
      attention.

PMID- 7514916
TI  - Dys- and paraproteinaemias in patients suffering from ophthalmic herpes zoster.
AB  - Humoral immune parameters were measured in 93 patients suffering from ophthalmic
      herpes zoster. The control group consisted of 31 other ophthalmic patients. In
      all cases, electrophoresis, immunoglobulins, acutephase proteins, immune
      complexes, antinuclear antibody and complement components were determined as
      well. In patients suffering from ophthalmic herpes zoster the main immunological
      deviations among the humoral parameters were found in the non-specific immune
      response. These alterations were comparable with the extent and severity of the
      pathological processes. Para-proteins were detected in 12% of the patients. In
      contrast they were not present in the control group.

PMID- 7514917
TI  - Surgical avulsion of the iris to treat selected cases of neovascular glaucoma.
AB  - Surgical avulsion of the iris was performed in 11 eyes of 11 patients affected
      with diabetic retinopathy, rubeosis of the iris and neovascular glaucoma that had
      been unsuccessfully treated otherwise. Nine eyes had extensive iris
      neovascularization, complicated cataract and vitreous haemorrhage, whereas the
      other two eyes were aphakic and had previously undergone vitrectomy, lensectomy
      and extensive laser photocoagulation. Prior to surgical avulsion of the iris, all
      eyes received topical and entheric hypotensive therapy. The intraocular pressure
      (IOP) ranged from 24 to 52 mmHg. Iris avulsion lowered the IOP in 9 of the 11
      eyes treated (IOP range, 6-19 mmHg).

PMID- 7514918
TI  - Insulin-like growth factors I and II are reduced in plasma from growth retarded
      children with chronic liver disease.
AB  - This study shows that blood from young children (< 3 years) with end stage liver
      disease, contains less IGF-I, IGF-II and IGFBPs than blood from normally growing
      children without liver disease, despite the provision of adequate calories. These
      low levels are likely to contribute to growth failure in children with end stage
      liver disease.

PMID- 7514919
TI  - Inhibition of gastric mucosal mucin receptor by Helicobacter pylori
      lipopolysaccharide.
AB  - A gastric mucosal mucin receptor has been isolated from the epithelial cell
      membrane by affinity chromatography on wheat germ agglutinin. The receptor
      protein displayed an apparent molecular weight of 97kDa and exhibited binding
      specific to gastric mucin in a concentration-dependent manner. The binding of
      mucin to the mucosal receptor was inhibited by lipopolysaccharide from H. pylori.
      The inhibitory effect was proportional to the concentration of lipopolysaccharide
      up to 30 micrograms/ml, at which concentration a 91% decrease in binding
      occurred. The results suggest that H. pylori lipopolysaccharide is capable of
      disrupting the integrity of mucus perimeter of gastric mucosal defense by
      interfering with epithelial cell-mucin binding.

PMID- 7514920
TI  - A colourimetric dye assay to detect anti-viral activity of interferons:
      sensitivity for measuring cellular responsiveness to interferons.
AB  - Colourimetric assays which rely on the conversion of metabolic dyes are becoming
      increasingly used for measuring cell proliferation and cytotoxicity. We developed
      a method for measuring cellular responsiveness to interferons based on the
      property of interferons to induce cell defenses to virus-mediated killing. The
      assay has several advantages over previous assays for measuring anti-viral
      activity and efficiently detected cytoprotective responses to human interferon of
      five human melanoma cell lines infected with Semliki Forest virus. The melanoma
      cell lines showed a varying cytoprotective response to interferons alpha 2, alpha
      4, beta and gamma, in agreement with the results of previous assays for measuring
      melanoma cell responsiveness to interferons based upon the inhibition of cell
      growth (1).

PMID- 7514922
TI  - Training of consultants in communicable disease control. History, present state,
      and future needs. The Working Group on Training for the Consultant in
      Communicable Disease Role.

PMID- 7514923
TI  - Training of consultants in communicable disease control. The evidence: results of
      three surveys. The Working Group on Training for the Consultant in Communicable
      Disease Role.

PMID- 7514924
TI  - Training of consultants in communicable disease control. Recommendations for
      education and in service training. The Working Group on Training for the
      Consultant in Communicable Disease Role.

PMID- 7514921
TI  - Regulation of insulin-like growth factor-I and binding protein-3 expression in
      oMtla-oGH transgenic mice.
AB  - Growth hormone (GH)-transgenic mice provide a model for studying hormonal
      regulation of gene products responsible for efficient lean growth. Insulin-like
      growth factor-I (IGF-I) and IGF binding protein-3 (BP-3) are two products
      involved in mediating the growth promoting actions of GH. Mice carrying the ovine
      metallothionein la-ovine growth hormone (oMtla-oGH) transgene were used to study
      GH regulation of IGF-I and BP-3 expression because these mice do not exhibit
      elevated basal oGH levels without transgene stimulation by exogenous zinc.
      C57B1/6XCBA mice with (transgenic = TG) and without control = C) the oMtla-oGH
      transgene were activated (+ Zn) or inactivated (-Zn) by the addition or removal
      of 25 mM zinc sulfate in the drinking water. Plasma IGF-I and BP-3 levels were
      determined by radioimmunoassay and western ligand blotting, respectively. Hepatic
      IGF-I and BP-3 mRNA levels were determined by slot-blot analysis. TG+Zn mice had
      higher plasma IGF-I (p < 0.05) and hepatic IGF-I mRNA (p < 0.05) levels as
      compared to TG-Zn, C+Zn and C-Zn mice. Plasma IGF-I and hepatic IGF-I mRNA levels
      in TG-Zn mice were not different from C+Zn and C-Zn mice. Removal of Zn decreased
      hepatic IGF-I mRNA levels to C levels in TG mice. Plasma BP-3 and hepatic BP-3
      mRNA levels in TG+Zn mice were increased (p < 0.05) as compared to TG-Zn, C-Zn
      and C+Zn. Plasma BP-3 and hepatic BP-3 mRNA levels did not differ between TG-Zn,
      C-Zn and C+Zn mice. Expression of the transgene also increased the level of
      plasma BP-3 during pregnancy as compared to that observed for pregnant C mice. We
      conclude that oGH regulates IGF-I and BP-3 expression in the oMtla-oGH transgenic
      mouse model system.

PMID- 7514925
TI  - An outbreak of gastrointestinal illness associated with contamination of the
      mains supply by river water.
AB  - In June 1992 a department of public health was informed of an outbreak of illness
      that was thought to be associated with contamination of the mains water supply to
      a farm. A field investigation identified 42 cases of acute gastrointestinal
      illness among 117 people potentially at risk, and found that the mains water
      supply to the farm was connected to an irrigation system that used water from a
      river. This outbreak illustrates the danger of connections between potable and
      non-potable water systems, and emphasises the importance of complying with
      existing water byelaws.

PMID- 7514926
TI  - 'COVER' (cover of vaccination evaluated rapidly): 29.

PMID- 7514927
TI  - Gastroenteritis associated with oysters.

PMID- 7514928
TI  - Task force for diphtheria in eastern Europe.

PMID- 7514929
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7514930
TI  - A case of infant botulism.

PMID- 7514931
TI  - Anticoagulants and the isolation of mycobacteria from blood.

PMID- 7514932
TI  - Health care workers infected with HIV: revised guidance.

PMID- 7514933
TI  - Cytokeratin expression in epithelial cells isolated from the crypt and villus
      regions of the rodent small intestine.
AB  - Many physiological and structural features of epithelium in the small intestine
      are regulated during their transit from the crypt base to the villus tip. This
      crypt-villus axis is an important model for the study of the regulation of cell
      proliferation and differentiation. We have investigated the expression of
      cytokeratins in purified epithelial cells from the proliferative (crypt) and
      differentiated (villus) regions of this tissue. Three polypeptides were
      identified (cytokeratins 8, 18 and 19) as well as a fourth, 46 kDa polypeptide
      with similar electrophoretic characteristics to the recently identified
      cytokeratin 20. The distribution of these molecules was found to vary along the
      crypt-villus axis, with cytokeratin 18 being restricted to the proliferative
      crypt and cytokeratins 8 and 19 demonstrating more uniform distributions. The 46
      kDa component was found to be expressed predominantly within the villus
      epithelium. Although there is no substantial evidence of a direct role for
      cytokeratins in the process of epithelial differentiation, these data suggest
      that differential expression of cytokeratins is associated with changes in
      intestinal epithelial differentiation.

PMID- 7514936
TI  - Management of malignant pleural effusions with pleuroperitoneal shunting.
AB  - Malignant pleural effusions are often debilitating conditions for the patient
      with advanced carcinoma. Traditionally, treatment has been repeated thoracentesis
      or tube thoracostomy with instillation of sclerosing agents. However, this
      required the patient to be hospitalized and to have pain and inconveniences of
      the chest tubes. The drainage also had to be low enough for sclerotherapy to be
      effective. In 1982, the pleuroperitoneal shunt became a feasible alternative to
      sclerotherapy. We began using the Denver pleuroperitoneal shunt in July 1991.
      Twenty shunts were inserted into 19 patients during a two year period ending June
      30, 1993. All patients but one were relieved of dyspnea. The mean duration of
      patency was 26 months and fewer than 25 percent of the shunts clotted before the
      death of the patient. Our favorable experience with the shunt has resulted in us
      recommending the Denver pleuroperitoneal shunt for treatment of recurrent
      malignant pleural effusions and selectively as primary treatment.

PMID- 7514935
TI  - Expression of pokeweed lectin binding in murine intestinal Paneth cells.
AB  - Pokeweed (Phytolacca americana) lectin was found to stain the secretory granules
      in epithelial Paneth cells of small intestine in mice and rats. The distribution
      of Paneth cells stained with this lectin was identical to that obtained by
      another immunohistochemical marker for lysozyme. However, in comparison with
      other immunohistochemical markers, Pokeweed lectin is a more robust method for
      identifying Paneth cells in histological sections and for studying their
      secretory granules. Co-expression of the Pokeweed lectin binding sites in some
      oligomucous cells within the crypts suggested a close developmental link between
      these two cell types. Only one other non-epithelial cell type was stained by this
      lectin, and these were migratory lymphocytes found within the villus epithelium
      and lamina propria. Approximately 20% of these lymphocyte cells were also
      positive for the expression of CD3+. Pokeweed lectin was therefore used to study
      changes in the frequency of Paneth cells and intra-epithelial lymphocytes in
      normal and immunologically compromised animals (following infection with a
      parasite worm Trichuris muris and in a model of graft-versus-host rejection).
      This study confirmed that the population of Paneth cells turns over slowly even
      during conditions of inflammation.

PMID- 7514934
TI  - An immunomagnetic separation method using superparamagnetic (MACS) beads for
      large-scale purification of human mammary luminal and myoepithelial cells.
AB  - A comparison has been made between different immunomagnetic techniques for
      separating normal human mammary epithelial cells based on the exclusive
      expression of EMA (epithelial membrane antigen) by luminal cells and CALLA (CD10)
      by myoepithelial cells. When cells labelled with antibodies to these antigens
      were incubated with Dynabeads, they rosetted myoepithelial but not luminal cells.
      However, both luminal and myoepithelial cells could be positively separated using
      the MACS system. Purity was established by analyzing the expression of CALLA and
      EMA using flow cytometry, and of cell-type specific cytokeratins using indirect
      immunofluorescence. Dynabead-separated myoepithelial cell populations were of
      high purity (> 98%) but the beads could not be removed from the cells. Luminal
      cell populations separated by the MACS method were also highly purified (> 95%),
      as were myoepithelial cell populations (> 90%). Using this immunomagnetic
      separation method, up to 10(7) cells of each type could be obtained from
      individual preparations.

PMID- 7514937
TI  - Adult adenohypophysial cells express beta 1 integrins and prefer laminin during
      cell-substratum adhesion.
AB  - beta 1 Integrins are a family of structurally related heterodimeric cell surface
      receptors that are involved in adhesion to molecules in the extracellular matrix
      (ECM) such as laminin (LN), fibronectin (FN), and collagen. These receptors are
      expressed by many cell types and mediate a variety of processes such as cell
      matrix and cell-to-cell adhesion, cell migration, growth, and differentiation.
      The purpose of these studies was to identify and partially characterize beta 1
      integrins on adenohypophyseal cells and to begin to elucidate their functional
      importance. Adenohypophyses were removed from adult male rats, dispersed using
      0.25% trypsin, rinsed, and resuspended in a 1:1 mixture of Dulbecco's modified
      Eagle's medium and F12 medium containing 10% fetal bovine serum and antibiotics.
      Ten million cells were allowed to attach to each of five plastic culture dishes
      overnight. The next day, the adenohypophyseal cells were surface-labeled with
      125I. The labeled cells were lysed and centrifuged. The supernatant was
      immunoprecipitated using preimmune IgGs (100 micrograms/ml) and was then
      incubated with a polyclonal antibody against the rat beta 1 family of integrins
      or with a variety of immune IgGs directed against the alpha subunit of the
      receptor (anti alpha 1, anti alpha 2, anti alpha 3, and anti alpha 5 antibodies).
      The receptors were then immunoprecipitated by addition of protein A-Sepharose or
      IgG1 Sepharose. After washing, the immunoprecipitates were subjected to sodium
      dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Cultured
      adenohypophyseal cells expressed the beta 1 integrin subunit, which was
      associated with the alpha 1, alpha 2, alpha 3, and alpha 5 integrin
      subunits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514938
TI  - Extracellular matrix-dependent differentiation of rabbit tracheal epithelial
      cells in primary culture.
AB  - The differentiation of tracheal epithelial cells in primary culture was
      investigated according to the nature of the extracellular matrix used. Cultures
      obtained by the explant technique were realized on a type I collagen substratum
      either as a thin, dried coating or as a thick, hydrated gel supplemented with
      culture medium and serum. These two types of substratum induced distinct cell
      morphology and cytokeratin expression in the explant derived cells. Where cells
      are less proliferating (from Day 7 to 10 of culture), differentiation was
      evaluated by morphologic ultrastructural observations, immunocytochemical
      detection of cytokeratins, and determination of cytokeratin pattern by
      biochemical analysis. The epithelium obtained on gel was multilayered, with
      small, round basal cells under large, flattened upper cells. The determination of
      the keratin pattern expressed by cells grown on gel revealed an expression of
      keratin 13, already considered as a specific marker of squamous metaplasia, that
      diminished with retinoic acid treatment. Present results demonstrated by confocal
      microscopy that K13-positive cells were large upper cells with a dense keratin
      network, whereas lower cells were positively stained with a specific monoclonal
      antibody to basal cells (KB37). Moreover, keratin neosynthesis analysis pointed
      out a higher expression of K6, a marker of hyperproliferation, on gel than on
      coating. All these data suggest a differentiation of rabbit tracheal epithelial
      cells grown on gel toward squamous metaplasia. By contrast, the epithelium
      observed on coating is nearly a monolayer of very large and spread out cells. No
      K13-positive cells were observed, but an increase in the synthesis of simple
      epithelium marker (K18) was detected. These two substrata, similar in composition
      and different in structure, induce separate differentiation and appear as good
      tools to explore the mechanisms of differentiation of epithelial tracheal cells.

PMID- 7514939
TI  - Tissue staining.
AB  - Tissue staining has broad clinical and research application in gastroenterology
      but remains underused. New application and the development of novel "stains"
      should result in improved detection of gastrointestinal disease. Expanded
      research in tissue staining is needed and data on outcome effectiveness awaited.

PMID- 7514940
TI  - Correlation of serum prostate specific antigen levels and bone scintigraphy in
      carcinoma prostate.
AB  - Serum prostate specific antigen (PSA) has been suggested as an accurate means of
      monitoring prostate cancer. An analysis of PSA levels and bone scan findings was
      carried out in a heterogeneous group of patients with a view to determine whether
      PSA can accurately predict bone metastases in carcinoma prostate. Of the 48
      patients studied, all 10 untreated cases had elevated PSA levels, eight having
      bone metastases. In 29 cases on follow-up after treatment of the primary, 10 out
      of 11 cases with normal PSA had a negative bone scan. In the nine who received
      hormonal therapy, the PSA levels were generally lower than others in the study
      group. Two out of four with normal PSA had bone metastases. In 26 cases with
      positive bone scans, 23 had elevated PSA levels (mean 109.9 ng ml-1). Among 22
      patients who had normal bone scans, all 10 with high PSA were found to have soft
      tissue disease which could explain the elevated PSA. In those with normal PSA, 12
      out of 15 patients had negative scans. PSA has fairly high sensitivity (86.5%)
      and negative predictive value (80%). But it suffers from low specificity (54.5%)
      and low positive predictive value (69.7%) for bone metastases. In an untreated
      patient with elevated PSA, a bone scan may be required to exclude bone
      metastases, whereas during follow-up after treatment, a normal PSA level may
      obviate a "routine" bone scan.

PMID- 7514942
TI  - Is "nonpropositional" speech preserved in aphasia?
AB  - Twenty-eight aphasic patients were tested on six tasks designed to assess
      "nonpropositional" speech and six matched tasks designed to assess propositional
      speech. The most reliable differentiation between nonpropositional and
      propositional speech type behaviors within a group of aphasics was found for the
      Numbers and Picture naming tasks. A smaller effect was observed on the Days of
      the week and Phrase repetition tasks. Only 6 of the 28 patients consistently
      showed a nonpropositional advantage across the range of task comparisons.
      However, a principal components analysis extracted two factors which
      differentiated propositional from nonpropositional tasks reasonably well. We
      conclude that nonpropositional speech, to the extent that it is measured by these
      tasks, is not preserved in aphasics as a group, though some patients may show a
      fairly consistent nonpropositional advantage. The distinction between
      propositional and nonpropositional speech does appear to have some application to
      aphasia, however. An error analysis supports the conjecture that propositional
      tasks involve semantic processing while nonpropositional tasks may place a
      greater load on phonological processing.

PMID- 7514941
TI  - An immunohistochemical study of the telencephalon and the diencephalon in a
      Myxinoid jawless fish, the Pacific hagfish, Eptatretus stouti.
AB  - The forebrain of adult hagfishes (jawless craniates, Myxinoidea) displays a
      unique morphology. The forebrain is thick-walled and well-differentiated
      cytoarchitecturally but lacks a well-developed ventricular system, and there is a
      pronounced compression of the entire brain along the longitudinal axis. This
      combination of characters obscures the boundaries between the major subdivisions
      of the forebrain; thus, some elementary morphological issues, such as the
      location of the pallial-subpallial and the telencephalic-diencephalic boundaries,
      have remained a matter of dispute over the past 100 years. In an attempt to
      resolve some of these issues, we investigated the chemoarchitecture of the
      forebrain of the Pacific hagfish, Eptatretus stouti. Because a number of previous
      studies of other craniates, mainly gnathostomes, have shown that the spatial
      distribution of some neuroactive substances and enzymes mirrors the main
      subdivisions of the forebrain, we localized acetylcholinesterase, enkephalins,
      substance P, tyrosine hydroxylase, and alpha-melanocyte stimulating hormone by
      means of histochemistry. Surprisingly, our data show that there are very limited
      chemoarchitectural similarities shared by hagfishes and other craniates. Some
      striking similarities occur in the organization of the catecholaminergic systems.
      Hagfishes, as well as other craniates, possess catecholaminergic cell groups at
      the ventral junction of the mesencephalon and diencephalon that give rise to a
      catecholaminergic innervation of the basal forebrain. The distribution of all
      other substances examined is dissimilar to that found in other craniates. In
      particular, there are many neurons positive for acetylcholinesterase in the
      pallium; the subpallium contains relatively small amounts of neuroactive
      peptides; and the highest densities of structures positive for neuroactive
      peptides and acetylcholinesterase occur in the central prosencephalic nucleus.
      Therefore, a comparative chemoarchitectural analysis proved to be of limited
      value in revealing homologies among cell groups of hagfishes, lampreys, and
      gnathostomes. We conclude that some chemoarchitectural features that appear to be
      well conserved within gnathostomes, such as the histochemical differences between
      the pallium and subpallium, may result from evolutionary change early in craniate
      history.

PMID- 7514943
TI  - Lack of error awareness in an aphasic patient with relatively preserved auditory
      comprehension.
AB  - The neuropsychological mechanisms underlying unawareness of speech/language
      deficits are unknown, but four possibilities have been suggested: impaired
      lexical-semantic representations associated with impaired speech comprehension, a
      failure of feedback, reduced attentional capacity, and psychological denial. We
      studied a patient who was unaware of his jargon aphasia despite only a mild
      auditory comprehension disturbance. Delaying auditory feedback altered his speech
      patterns. He recognized more of his errors in a recording of his voice than he
      did while speaking. He also recognized more errors in a recording of the examiner
      making errors than he did when listening to the recordings of his own speech.
      Based on these results, we suggest that none of the proposed mechanisms can
      exclusively account for this man's performance and that each may contribute to
      his failure to detect and correct errors in speech production.

PMID- 7514945
TI  - Peripheral nerve stimulation increases serotonin and dopamine metabolites in rat
      spinal cord.
AB  - Extracellular serotonin (5-HT), dopamine (DA), and their metabolites, 5
      hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and
      homovanillic acid (HVA), were assessed in the rat lumbar spinal cord (L3-4) by in
      vivo microdialysis with high performance liquid chromatography and
      electrochemical detection (HPLC-ECD). Under urethane-chloralose anesthesia, basal
      levels of 5-HT and DA in the dialysates were approximately 1.0-1.2 pg/22
      microliters sample, 5-HIAA, DOPAC, and HVA were constant at 322.6 +/- 14.9, 8.6
      +/- 0.7, and 10.4 +/- 0.4 pg/22 microliters sample (mean +/- SE), respectively.
      Local application of 100 mM KCl via the dialysis probe increased the 5-HT and DA.
      Peripheral nerve stimulation that selectively excited the large (A-beta) or small
      (A-delta) myelinated fibres increased the metabolites. Excitation of the A-beta
      fibers increased the levels of 5-HIAA to 138%, DOPAC to 155%, and HVA to 143% of
      the controls. Stimulation of the A-delta fibers increased 5-HIAA to 121%, DOPAC
      to 120%, and HVA to 124% of the controls. The results suggest that non
      nociceptive peripheral nerve stimulation may activate the descending 5-HT and DA
      systems in the spinal cord.

PMID- 7514944
TI  - Speech timing at the sentence level in Thai after unilateral brain damage.
AB  - The present study examined temporal characteristics of spoken sentences in Thai
      to evaluate timing control in brain-damaged patients with unilateral left and
      right hemisphere lesions. Subjects included 10 young and 10 old normal adults, 14
      right hemisphere patients, and 2 left hemisphere nonfluent and 7 fluent aphasic
      patients. Utterances were produced at a conversational speaking rate. Duration
      measures were taken from wide-band spectrograms. Results indicated that left
      hemisphere patients exhibited abnormal timing on both absolute and relative
      timing measures, whereas right hemisphere patients did not. Among left hemisphere
      patients, fluent as well as nonfluent aphasics exhibited aberrant temporal
      patterns. Left hemisphere patients were also more variable than right hemisphere
      patients which, in turn, were more variable than normals in their production of
      sentences. In comparison to earlier findings on timing at segment and word
      levels, it was found that deficit profiles varied between fluent and nonfluent
      aphasics as a function of the size of the linguistic unit with nonfluent aphasics
      being affected at the segment, word, and sentence level but fluent aphasics
      affected at the sentence level only. Findings are discussed in relation to issues
      pertaining to hemispheric specialization and the nature of timing deficits in
      nonfluent and fluent aphasic patients.

PMID- 7514946
TI  - The WAG/Rij rat model for nonconvulsive absence epilepsy: involvement of nonNMDA
      receptors.
AB  - The involvement of AMPA and kainate receptors in nonconvulsive epilepsy was
      studied by intracerebroventricular injections of AMPA, GDEE, kainic acid and
      kynurenic acid in WAG/Rij rats. The WAG/Rij rat strain is recognized as an animal
      model for human absence epilepsy. EEG registrations showed that AMPA (0.1 pmol/5
      microliters; 1 pmol/5 microliters; 10 pmol/5 microliters) dose-dependently
      increased the nonconvulsive absence epilepsy while GDEE (0.2 mumol/5 microliters;
      1 mumol/5 microliters; 5 umol/5 microliters) caused a dose-dependent decrease.
      All effects of GDEE could be blocked by an inactive AMPA dosage. Kainic acid
      (0.01 nmol/5 microliters; 0.1 nmol/5 microliters; 0.15 nmol/5 microliters) had no
      effects on the nonconvulsive epilepsy but induced convulsions in the two highest
      dosages. Kynurenic acid (50 nmol/5 microliters; 100 nmol/5 microliters; 500
      nmol/5 microliters) decreased dose-dependently the incidence of nonconvulsive
      epilepsy. The effect of kynurenic acid could be blocked by a nonconvulsive dosage
      of kainic acid. These results show that the AMPA and kainate receptor appear to
      be involved in nonconvulsive epilepsy. Furthermore, blockage of these two
      receptor subtypes led to an antiepileptic effect without inducing behavioural
      alterations. Therefore, selective AMPA and kainate receptor antagonists might be
      potent anti-epileptics.

PMID- 7514947
TI  - Interactions between NMDA and nonNMDA receptors in nonconvulsive epilepsy in the
      WAG/Rij inbred strain.
AB  - The interaction between NMDA and nonNMDA receptors was studied in nonconvulsive
      epilepsy in WAG/Rij rats. Compounds acting on NMDA (NMDA, APH) and nonNMDA (AMPA,
      GDEE, kainic acid, kynurenic acid) receptors were coinjected
      intracerebroventricularly. The WAG/Rij rat strain may be an animal model for
      human nonconvulsive absence epilepsy. The effects on the epilepsy, EEG and
      behaviour were measured. It appeared that the epilepsy increase, induced by the
      nonNMDA receptor agonist AMPA, and in a less obvious way, kainic acid, was
      blocked by the NMDA receptor antagonist APH. The effects of NMDA were completely
      blocked by the nonNMDA receptor antagonists GDEE and kynurenic acid. These
      results suggest that there is an interaction between NMDA and nonNMDA receptors.
      It might be that nonNMDAergic compounds act via activation or inactivation of
      NMDA receptors and that this latter receptor subtype is the trigger for an
      epileptic seizure.

PMID- 7514948
TI  - Ultrastructural and immunohistochemical study of the telencephalo-habenulo
      interpeduncular connections of the goldfish.
AB  - Surgical ablations of telencephalon or telencephalon plus habenular nuclei (HBN)
      have been performed for studying anatomical connections of the telencephalo
      habenulo-interpeduncular system of the goldfish. The results of the
      ultrastructural studies confirmed the presence of massive telencephalo-habenular
      and habenulo-interpeduncular projections and, in addition, demonstrated a minor
      direct telencephalo-interpeduncular connection. Immunohistochemical localization
      of substance P in the interpeduncular nucleus (IPN) after telencephalic ablation
      failed to demonstrate the involvement of this neurotransmitter in the direct
      telencephalo-interpeduncular projection, while telencephalon plus HBN ablation
      reduced substance P immunoreactivity in the IPN. The different distribution of
      degenerating terminals converging on the IPN from the HBN and from the
      telencephalon suggested a subnuclear organization of this area, as described in
      mammals.

PMID- 7514949
TI  - Nucleotide sequence statistical analysis of pauses in RNA elongation by
      Escherichia coli RNA polymerase.
AB  - A convenient motif-searching program has been developed, based on a double
      correlation algorithm, for analysis of the pulse character of Escherichia coli
      transcription. Activity in the zone of minimal pause formation (-1,2 bp) is
      precisely determined. Oligonucleotides (di-, tri- and tetranucleotides) are
      randomized by their pause-generating activity. 'CATG' and 'CATGC' are detected
      which coincide with the primary structure of RNA associated with distinctive
      delays in biologically meaningful situations.

PMID- 7514950
TI  - A Macintosh program for the versatile generation of random nucleic acid sequences
      and their structural analysis.
AB  - The program 'MacStAn' for the Apple Macintosh generates random sequences and can
      analyze their tendency to form secondary structure or translation products as
      well as their mono-, di- and trinucleotide composition. Generation of random
      sequences is versatile in that one can (i) predefine the G+C content, maximal
      base repetitions and constant regions; (ii) preset the entire dinucleotide
      composition; or (iii) shuffle an existing sequence. The program constitutes an
      integrated package with a graphical user interface, full-featured editing,
      saving, printing, text import and export, dot plot and sequence alignment.

PMID- 7514951
TI  - SIMPLE34: an improved and enhanced implementation for VAX and Sun computers of
      the SIMPLE algorithm for analysis of clustered repetitive motifs in nucleotide
      sequences.
AB  - SIMPLE34 is an improved and enhanced version of SIMPLE for Vax and SunOS systems.
      It now provides a length-independent measure of the overall level of tri- and
      tetranucleotide motif clustering within nucleotide sequences and its significant
      deviation from random expectation. It now also provides information on tri- and
      tetranucleotide motifs showing higher levels of clustering than would be expected
      in random sequences. Sequence simplicity of test sequences can be judged with
      respect to random sequences generated on the basis of base composition,
      positional base composition or doublet frequency. These options can be used to
      investigate factors resulting in sequence simplicity.

PMID- 7514952
TI  - Magnetic resonance imaging of splenic hemangiomatosis.
AB  - The authors report a case of splenic hemangiomatosis evaluated by magnetic
      resonance imaging (MRI). Typical areas of hyperintensity were observed in T2
      weighted images. Because it is noninvasive and highly sensitive, MRI proved
      valuable in suggesting the diagnosis in this patient.

PMID- 7514953
TI  - Assessment of urinary beta-core fragment of human chorionic gonadotropin as a new
      tumor marker of lung cancer.
AB  - BACKGROUND: Some patients with lung cancer have been found to have elevated
      levels of serum immunoreactive human chorionic gonadotropin (hCG)/hCG beta (IR
      beta), but it is uncertain whether it would be valuable as a tumor marker.
      Recently, IR-beta has been demonstrated to consist of at least three different
      molecules, intact hCG, free hCG beta, and hCG beta-core fragment (beta-CF), in
      body fluids. In this study, the authors qualitatively analyzed IR-beta in the
      serum and urine of patients with lung cancer and assessed its clinical usefulness
      as a tumor marker. METHODS: Highly sensitive and specific enzyme immunoassays
      were established to measure intact hCG, free hCG beta, and beta-CF in the serum
      and urine of patients with lung cancer. RESULTS: Of 99 patients with lung cancer,
      almost half of the patients achieved positive values of IR-beta in the urine,
      although only 12 had elevated values of IR-beta in the serum. The greater part of
      the elevated urinary IR-beta was identified to be beta-CF by gel chromatography
      on Sephadex G-100 (Pharmacia LKB Biotechnology, Tokyo, Japan), leading the
      authors to assess its usefulness as a tumor marker for lung cancer. Based on the
      cutoff value (0.2 ng/mg of creatinine) from healthy subjects, the overall
      positive rate of urinary beta-CF for lung cancer was 48.5% (48 of 99 patients).
      The incidence of the marker increased with stage of disease, from 35.7% (15 of
      42) in Stage I and 35.7% (5 of 14) in Stage II to 62.5% (20 of 32) in Stage III
      and 72.7% (8 of 11) in Stage IV. These positive rates exceeded or equaled those
      of the serum tumor markers, carcinoembryonic antigen, and squamous cell carcinoma
      (SCC)-related antigen, measured simultaneously in the same patients. The author
      were encouraged that there was no significant difference in the positive rates of
      urinary beta-CF between two major types of lung cancer: adenocarcinoma (49.2%)
      and SCC (45.2%). Immunohistochemical study revealed positive staining of IR-beta
      in the cancer tissues from 5 of 12 patients with elevated levels of IR-beta, in
      which most of the positive cases had the elevated levels of serum free hCG beta
      (> 0.5 ng/ml) and/or urinary beta-CF (> 1.0 ng/mg of creatinine). CONCLUSIONS:
      Ectopic production of IR-beta by lung cancer is not rare, and urinary beta-CF
      might be a potential tumor marker of lung cancer.

PMID- 7514954
TI  - Detection of HER-2/neu oncogene amplification in flow cytometry-sorted breast
      ductal cells by competitive polymerase chain reaction.
AB  - BACKGROUND: The amplification and/or overexpression of the HER-2/neu oncogene has
      been proposed as an important prognostic marker in breast cancer. However,
      contradictory results from various groups regarding whether there is statistical
      significance in HER-2 amplification or overexpression in predicting overall and
      disease free survival in node positive versus node negative patients exist in the
      literature. Current assays on quantifying the HER-2 oncogene rely on DNA
      extracted from homogenized breast tissue. Not only is a large amount of tissue
      required, but also, the DNA extract is contaminated with DNA from stromal cells
      and leukocytes, leading to decreased specificity and sensitivity of the HER-2
      assay. Improving the specificity (DNA from breast ductal cells) and the
      sensitivity (competitive polymerase chain reaction [PCR]) of the HER-2
      amplification detection assay will help resolve some of these controversies.
      METHODS: Using multiparameter flow cytometry (FCM), ductal cells from breast
      biopsies and fine needle aspirations (FNAs) are identified and selectively sorted
      using anti-cytokeratin, anti-HER-2 antibody labeling and DNA staining. HER-2
      amplification in these sorted cells is then quantified by competitive DNA PCR
      using a competitive reference standard mutant template that is susceptible to the
      restriction enzyme Sma-1. RESULTS: Applying this strategy, SK-BR-3, an HER-2
      amplified breast cancer cell line, was found to have approximately 9x baseline
      HER-2 oncogene copies. In addition, MCF-7, a known HER-2 nonamplified breast
      cancer cell line, was found to have baseline HER-2 oncogene copies. In the 10
      clinical breast samples tested, 4 of the 10 breast cancers were HER-2 amplified
      using as few as 1000 cells. The cytokeratin positive cells of these cancers, in
      contrast to the cytokeratin negative cells, have detectably higher HER-2
      amplification (7.2 +/- 2.8x versus 3.2 +/- 1.1x, respectively). Hence, HER-2 gene
      amplification would have been underestimated if unsorted cells were used because
      of stromal dilution. In the cytokeratin positive cells that were HER-2 oncogene
      amplified, corresponding HER-2 oncoprotein overexpression was detected by FCM.
      CONCLUSIONS: Using FCM, the ductal cell subpopulation of a breast specimen can be
      successfully sorted from breast biopsy and FNA specimens. Moreover, by applying
      the technique of competitive PCR, improved specificity and sensitivity in HER-2
      oncogene amplification detection is achieved. The entire procedure can be
      accomplished in 1 day, allowing for a cost-effective assay and rapid turnaround
      time.

PMID- 7514957
TI  - Denial: coping or cop-out?
AB  - Health caregivers working with palliative patients in the home are able to
      establish closer relationships with these patients than in the palliative
      hospital setting. Since a familiar and comfortable setting helps set the stage
      for effective communication, it is not surprising that home care patients and
      their families often share intimate thoughts and feelings with visiting
      caregivers. Yet that same closeness can make it more difficult for a home
      caregiver to accept a patient's denial of impending death. While agreeing that,
      in theory, denial is a normal defence mechanism, the home caregiver may have
      become too emotionally involved to appreciate denial as a particular patient's
      choice.

PMID- 7514956
TI  - Platinum-DNA adducts assayed in leukocytes of patients with germ cell tumors
      measured by atomic absorbance spectrometry and enzyme-linked immunosorbent assay.
AB  - BACKGROUND: Platinum-DNA adducts can be measured in peripheral blood cells, and
      high adduct levels have previously been correlated with favorable clinical
      response to platinum-based therapy in patients with germ cell tumors and ovarian
      cancer. METHODS: To evaluate the relationship between platinum-DNA adducts and
      clinical response to chemotherapy, 36 patients with germ cell tumors treated with
      cisplatin-based chemotherapy had platinum-DNA adducts assayed in leukocytes by
      atomic absorption spectrometry (AAS) and cisplatin-DNA enzyme-linked
      immunosorbent assay (ELISA). Three chemotherapy regimens were involved: cisplatin
      and etoposide (Regimen A); carboplatin and etoposide (Regimen B); and
      cyclophosphamide, vinblastine, dactinomycin, bleomycin, and cisplatin [VAB-6]
      with or without high dose carboplatin plus etoposide plus autologous bone marrow
      rescue (Regimen C). Blood samples were drawn before and after each cycle of
      chemotherapy. RESULTS: One hundred ninety-two blood samples were assayed by AAS
      and 137 by ELISA: DNA adducts measured by AAS and ELISA increased immediately
      after treatment and decreased during the intervening time before the next
      treatment. DNA adducts were measurable by both methods 4-8 weeks after the last
      cycle of therapy. The peak and mean adduct levels measured in samples drawn
      immediately after Cycles 1 and 2 and after all cycles were analyzed in terms of
      their relationship to clinical response. In contrast to numerous prior studies, a
      positive correlation was not observed between DNA adduct formation as determined
      by either AAS or ELISA and favorable clinical responses. CONCLUSIONS: This study
      demonstrated that peak and mean platinum-DNA adduct levels were influenced by the
      dose and schedule of the platinum analogue. For example, treatment with VAB-6
      with or without high dose carboplatin and etoposide (Regimen C) resulted in
      significantly higher adduct levels when measured by AAS compared with Regimen A
      or B. Inconsistencies between studies regarding observed correlations of DNA
      adducts and treatment outcome may be attributable to differences in platinum
      analogue, dose, schedule, and timing of sample procurement. These factors must be
      considered in future studies.

PMID- 7514955
TI  - Protection of thyroid cancer cells by complement-regulatory factors.
AB  - BACKGROUND: Clinical and experimental studies have suggested that complement
      activation may play a role in tumor cytotoxicity. Little information is available
      concerning the presence of complement activation and the localization of
      complement-regulatory factors in cells or tissues of malignant tumors. The aim of
      the present study was to examine, using immunohistochemistry and immunoelectron
      microscopy, whether the complement system is activated in tissues of thyroid
      carcinoma and whether thyroid carcinoma cells are protected from cell lysis by in
      situ complement activation. METHODS: Fresh tissues were obtained by thyroidectomy
      from 15 patients with papillary carcinomas, 7 with follicular carcinomas, and 5
      with follicular adenomas. In addition, five specimens of histologically normal
      thyroid tissue and five specimens of chronically inflamed tissue adjacent to
      thyroid neoplasms were studied. Immunohistochemical and immunoelectron
      microscopic localization of complement components, C3d and C5b-9, and the
      complement-regulatory factors, such as s-protein, decay-accelerating factor
      (CD55), membrane cofactor protein (CD46), complement receptor types 1 (CD35) and
      2 (CD21), and protectin (CD59), were examined in these tissues. RESULTS: The
      staining patterns of C3d, C5b-9, and s-protein were positive and homogeneous in
      the nonneoplastic and most neoplastic thyroid tissues. Immunoelectron microscopy
      showed these antigens were localized mainly on the subepithelial and vascular
      basement membranes and attached to the cell surface of thyroid follicular cells.
      Decay-accelerating factor (CD55) was present homogeneously on the basement
      membranes, on the basal cell border of the thyroid follicular cells, and often on
      the luminal surface of carcinoma cells. Both membrane cofactor protein (CD46) and
      protectin (CD59) were expressed strongly on the cell surface of almost all benign
      and malignant thyroid follicular cells. Membrane cofactor protein was expressed
      on both the basal and lateral membrane, showing cell-to-cell interaction, but
      rarely on the luminal surface, whereas protectin was expressed strongly on the
      luminal surface and often on the basal cell border but rarely on the lateral
      membrane. Neither complement receptor type 1 (CD35) nor complement receptor type
      2 (CD21) was expressed on any thyroid follicular cells. CONCLUSIONS: The present
      study confirmed the presence of complement activation with subsequent deposition
      of C3d and C5b-9 complexes in thyroid carcinomas. It also indicated that thyroid
      carcinoma cells are protected from cell lysis because of complement activation in
      multiple phases by complete coverage of the entire cell membrane surface with
      complement-regulatory factors. These findings were similar to those found in
      nonneoplastic thyroid follicular cells.

PMID- 7514958
TI  - Changes in monoaminergic neuronal function in the lower brain stem following
      subarachnoid hemorrhage induced in rats.
AB  - 1. We investigated the function of monoaminergic neurons in the lower brain stem
      following subarachnoid hemorrhage (SAH) induced in rats, by measuring monoamine
      metabolites, using in vivo microdialysis techniques. 2. A dialysis probe was
      implanted in the nucleus tractus solitarius (NTS) and the perfusates were assayed
      by high-performance liquid chromatography (HPLC) with electrochemical detection
      (ECD). 3. The main monoamine metabolites measured in the NTS extracellular space
      were 3,4-dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA) and 5
      hydroxyindoleacetic acid (5-HIAA). 4. Monoamine metabolites in the rat NTS were
      nonspecifically increased, at least in the acute phase after cisternal injection
      of blood or saline. 5. The disappearance rates of the 5-HIAA decline and the
      early phase of DOPAC decline after pargyline administration (75 mg/kg, i.p.) were
      most rapid at 2 days after the induction of SAH, then recovered gradually. 6.
      These results suggest that functions of noradrenergic and serotonergic neurons in
      the NTS may be disturbed predominantly in the case of induced vasospasm in rats.

PMID- 7514960
TI  - Selenium in the maintenance and therapy of HIV-infected patients.
AB  - Due to its antiviral effects and its importance for all immunological functions,
      the administration of selenium is suggested as a supportive measure in early as
      well as in advanced stages of HIV-induced disease. Initial observations on the
      effects of selenium supplementation in HIV-infected patients indicate that
      selenium causes symptomatic improvements and possibly slows the course of the
      disease. As selenium inhibits reverse transcriptase activity in RNA-virus
      infected animals, supplemental selenium could also prevent the replication of HIV
      and retard the development of AIDS in newly HIV-infected subjects. An adequate
      supply of selenium and of antioxidant vitamins is also proposed as a measure to
      reduce the probability of the placental transmission of HIV in pregnancy.

PMID- 7514959
TI  - Valproic acid reduces the intracellular level of glutathione and stimulates human
      immunodeficiency virus.
AB  - Modifications of the glutathione (GSH) intracellular level have been implicated
      in the regulation of human immunodeficiency virus (HIV) transcription and
      expression. In regard to this hypothesis, we have investigated the effects of
      valproic acid (VPA) on HIV replication. Indeed, it has been recently reported
      that VPA inhibits the human red blood cell glutathione reductase. In the
      supernatant of a CEM-SS T-lymphocytic cell line infected with the LAI strain of
      HIV-1, we observed an increase, in a dose-dependent fashion, of the reverse
      transcriptase activity after treatment of cells with VPA. VPA also induced HIV
      expression in the chronically infected monocytic U1 cell line which
      constitutively expresses low levels of virus, enhanced the HIV-long terminal
      repeat (LTR)-directed expression of beta-galactosidase in transiently transfected
      Jurkat T-cells, and potentiated the PMA effect on the LTR transactivation. GSH
      assays showed that VPA treatment led to a decrease in the intracellular level of
      this thiol compound in U937 (U1 parent-cell line) and in Jurkat T-cells. Work to
      understand the molecular mechanism of VPA-induced HIV transcription and
      expression are now in progress. VPA seems to be an adequate molecule to study the
      implications of a GSH decrease in the stimulation of HIV replication. However, a
      modification of the intracellular balance between reduced and oxidized
      glutathione, rather than a simple reduction of the intracellular glutathione
      level, could be of importance in the regulation of HIV replication and we are now
      testing this hypothesis. Finally, these findings already suggest that VPA, which
      is an anticonvulsive drug frequently prescribed for the management of various
      seizure disorders, should not be recommended for treatment of epilepsy or other
      related illnesses in HIV-positive individuals.

PMID- 7514961
TI  - Mechanistic aspects of ascorbate inhibition of human immunodeficiency virus.
AB  - We have investigated the molecular basis of the inhibitory effect of ascorbate
      (vitamin C) on human immunodeficiency virus (HIV) expression in unstimulated
      chronically infected and reporter cell lines. Comparison of intracellular HIV RNA
      and protein patterns of ascorbate-treated cells with corresponding patterns of
      untreated controls, did not show significant differences in the synthesis or
      processing of individual viral RNA and polypeptides, indicating that the
      inhibitory effect of ascorbate is not directed at steps of viral transcription or
      translation. Enzyme assays on cell extracts showed that the activity of an HIV
      LTR-directed reporter protein made in ascorbate-treated cells was reduced to
      approximately 11% relative to that of untreated control. These results, combined
      with previous observations on the suppression of HIV RT activity, are consistent
      with a mechanism of action in which ascorbate exerts a posttranslational
      inhibitory effect on HIV by causing impairment of enzymatic activity.

PMID- 7514964
TI  - The keratocyte density of human donor corneas.
AB  - The cellularity of the human corneal stroma has not been described in the
      literature. In the present study we calculated the density of keratocytes in
      human donor corneas using a new method for biochemical measurement of the stromal
      DNA content (sDNA). The DNA measurements were compared to morphological counts of
      the number of keratocyte nuclei per area (KNPA) obtained from histological
      sections. A significant correlation was found between the data achieved by the
      two methods (r = +0.52, p < 0.001, n = 46). No significant change in either sDNA
      or KNPA was found during 28 days of organ culture, and no influence of donor age,
      sex, or post mortem time was found on either sDNA or KNPA. Both sDNA and KNPA
      approximated a normal distribution with a mean sDNA of 1.10 +/- 0.25 micrograms
      DNA/mg dry tissue weight and an average KNPA of 200 +/- 53 nuclei/mm2 (n = 35).
      Between paired corneas the sDNA were closely correlated (r = +0.83, p < 0.005, n
      = 11 pairs) with an intra-individual variation of only 0.5%. Using the sDNA data,
      the keratocyte density in the central region of human donor corneas was
      calculated to be 129,000 +/- 29.000 per mg dry tissue weight (n = 35). Thus, when
      corneal grafting is performed (using a 7 mm trephine) an average of 818,000 +/-
      186,000 donor keratocytes are transplanted. Assuming a uniform cellularity
      throughout the stroma, the average number of keratocytes was calculated to be
      2,430.000 +/- 551,000 per human donor cornea.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7514963
TI  - A phase II evaluation of fazarabine in high-grade gliomas: a Southwest Oncology
      Group study.

PMID- 7514967
TI  - [Laparoscopic Kader fistula].
AB  - A laparoscopic modification of a gastrostomy by a catheter following the method
      first described by Kader is presented. Characteristic features are large luminal
      catheters being introduced into the stomach over a guide-wire and a special
      trocar under laparoscopic control. The gastric wall is additionally attached to
      the abdominal wall by laparoscopically applied sutures. Advantages and
      disadvantages of the presented method are compared and discussed to alternative
      and established procedures.

PMID- 7514962
TI  - Inhibition of induced angiogenesis in a human microvascular endothelial cell line
      by ET-18-OCH3.
AB  - Alkyl-lysophospholipids are a group of anti-cancer compounds that have previously
      been shown to have the unique feature of being selectively toxic to neoplastic
      tissues. One of these compounds, ET-18-OCH3, has been used for purging bone
      marrow of cancer cells in phase I clinical trials. Tumor-induced angiogenesis has
      been directly correlated with tumor growth and metastasis. In this study, we
      examined the effect ET-18-OCH3 has on a human microvascular endothelial cell line
      (HMEC-1), including the following functions: angiogenesis, cell-adhesion molecule
      expression, and cell-junction integrity. We found that ET-18-OCH3 (in vitro)
      reversibly inhibited induced angiogenesis at levels that did not affect
      viability. At lower concentrations, ET-18-OCH3 down-regulated the expression of
      cell-adhesion molecules and affected the integrity of cell-to-cell junctions.
      This observation demonstrates this versatile family of compounds to have
      additional targets of action.

PMID- 7514966
TI  - [Adjuvant and palliative therapy of melanoma. Current status].
AB  - Even though there are a couple of therapeutic concepts for the metastatic
      malignant melanoma and new protocols are being designed there is no cure for this
      tumor in the advanced stage. By carefully analyzing the results surgical therapy,
      radiation and chemotherapy can be named as the standard therapies. But different
      protocols of combined chemo- and immunotherapy, adjuvant therapies e.g. with
      tumor vaccines are being tried out. Experimental approaches are photodynamic
      therapy, the application of monoclonal antibodies and gene therapy.

PMID- 7514968
TI  - [The use of published personal photos in the education of medical students].

PMID- 7514965
TI  - Basic fibroblast growth factor experimentally induced choroidal angiogenesis in
      the minipig.
AB  - Basic fibroblast growth factor (bFGF), a soluble mitogen, has been isolated and
      purified from various organs, including the retina. In vivo angiogenic activity
      of bFGF has been demonstrated with several assays. An experimental model of
      choroidal neovascularization was developed in the mini pig by perfusion of
      recombinant human bFGF through an osmotic minipump. Endogenous bFGF and bFGF
      receptors were localized in the normal pig retina by immunohistochemistry and
      autoradiography after binding. The perfusion of exogenous bFGF induced well
      organized new vessels along the last 3 mm of the catheter in the suprachoroidal
      space. This neovascularization did not penetrate the normal Bruch's membrane.
      Vascular cells (identified by von Willebrand factor antibody staining) increased
      in number and in surface from the proximal part to the end of the intraocular
      catheter in all bFGF perfused eyes. In eyes perfused with phosphate buffered
      saline (controls), but not in the bFGF perfused eyes, an inflammatory response
      occurred (identified by a macrophage specific antibody). These results
      demonstrate that choroidal angiogenesis can be achieved without an inflammatory
      response by perfusing an excess of bFGF in the suprachoroidal space.

PMID- 7514969
TI  - [Adjuvant and palliative therapy for colorectal carcinoma].

PMID- 7514970
TI  - Melanoma vaccines. Current status and future prospects.

PMID- 7514974
TI  - Managing illicit drug use. A practical guide.
AB  - Illicit drug use is spreading, especially in the developing world, but has begun
      to stabilise in most developed countries. The phenomenon of illicit drug use is
      still poorly understood, with responses in most countries influenced largely by
      cultural factors. A range of psychosocial and pharmacotherapeutic treatments is
      available; of these, methadone maintenance treatment for heroin dependence has
      the most evidence of benefit. A large body of literature--including some well
      designed studies--indicates that methadone reduces heroin use, mortality,
      criminal activity and risk of human immunodeficiency virus (HIV) infection.
      Methadone is more likely to be effective if higher doses, longer durations of
      treatment and more realistic goals are set. However, research findings which
      would improve outcomes considerably are often not implemented. Methadone
      maintenance programmes, which attract and retain more illicit drug users than
      other treatment modalities, are now being made more available in many countries
      in recognition of their therapeutic effectiveness and utility in reducing the
      spread of HIV infection among people injecting heroin. HIV infection is now
      recognised in many countries to be the most serious complication of illicit drug
      use for both individual drug injectors and their communities. Levo-alpha
      acetylmethadol (LAAM) has similar properties to methadone but a longer half-life.
      This suggests a number of clinical benefits which would also reduce the cost of
      treatment. However, LAAM has not been approved by regulatory authorities for
      routine use despite positive findings in some studies. Buprenorphine has shown
      some promise in the management of heroin dependence but is still undergoing
      evaluation. It is, however, unlikely to ever be used widely for the management of
      illicit drug users. Naltrexone may have some advantages for special populations.
      Pharmacotherapeutic treatment for cocaine and amphetamine users is still at a
      developmental stage.

PMID- 7514973
TI  - Acromegaly. Recognition and treatment.
AB  - Acromegaly is a chronic debilitating disease caused by growth hormone (GH)
      hypersecretion, usually from a pituitary adenoma. It is frequently diagnosed
      after many years of active GH hypersecretion, and causes significant morbidity
      and mortality due to cardiac, pulmonary and musculoskeletal changes. Local
      complications resulting from the pituitary tumour can also occur. The most
      important feature that will enable a physician to diagnosis the disease is
      clinical vigilance. Measurement of elevated plasma mecasermin (insulin-like
      growth factor I, IGF-I) is the single best test to make the diagnosis. Once the
      diagnosis is confirmed, a GH-secreting tumour should be sought, by performing a
      careful magnetic resonance imaging or computed tomography scan of the pituitary
      gland and hypothalamus. Therapy is directed at both preventing local
      complications of the tumour mass as well as normalising GH secretion. Surgical
      resection of the tumour is almost always the first step in treatment. If GH
      secretion is not normalised, which is best assessed by determining whether plasma
      IGF-I returns to the normal range, further treatment with radiation and/or
      medical therapy is required. Bromocriptine normalises GH in approximately 10% of
      patients and causes pituitary shrinkage in a similar fraction of patients.
      Octreotide is considerably more expensive than bromocriptine and is given
      subcutaneously, but is more effective in both normalising GH secretion and in
      shrinking tumours. Octreotide treatment of the pituitary tumours prior to
      surgical resection may be of value, but requires further investigation.

PMID- 7514975
TI  - Pharmacological treatment of gallstones. Practical guidelines.
AB  - Laparoscopic cholecystectomy is the treatment of choice for symptomatic
      cholelithiasis. Medical treatment is indicated for patients who are not fit or
      are afraid of surgery. For any form of medical treatment to be effective
      gallstones must be cholesterol rich, thus radiolucent, and the cystic duct must
      be patent, as indicated by gallbladder opacification on oral cholecystography.
      Three forms of medical treatment are currently available for clinical use--oral
      bile acids, bile acids as adjuncts to lithotripsy and contact dissolution using
      methyltertbutylether. The choice of treatment depends mainly on gallstone size.
      Gallstones < 6 mm in diameter are best treated with oral bile acids,
      chenodeoxycholic acid 15 mg/kg/day or ursodeoxycholic acid 10 mg/kg/day given
      alone or in combination (5 mg/kg/day each). Careful patient selection and bedtime
      administration of the whole daily bile acid dose enhance treatment, and may
      achieve up to 75% complete dissolution annually. Single stones < 30 mm in
      diameter or multiple stones (n < 3) are best treated with lithotripsy combined
      with oral bile acid for dissolution of fragments. Annual dissolution rates are
      about 80 and 40% for single and multiple stones, respectively. Stones of any size
      and number can be dissolved by direct contact dissolution using
      methyltertbutylether. Dissolution has been reported to be complete in almost 100%
      of stones, but debris is frequently left behind in the gallbladder. Following
      dissolution using any form of treatment, gallstones recur in about 50% of
      patients, and cannot be reliably prevented by low dose bile acid or dietary
      manipulations. Failing prevention, early detection and retreatment of recurrent
      stones is the best alternative option as a long term strategy.

PMID- 7514976
TI  - Cefepime. A review of its antibacterial activity, pharmacokinetic properties and
      therapeutic use.
AB  - Cefepime is a 'fourth' generation cephalosporin that has a broader spectrum of
      antibacterial activity than the third generation cephalosporins and is more
      active in vitro against Gram-positive aerobic bacteria. The fact that cefepime is
      stable to hydrolysis by many of the common plasmid- and chromosomally-mediated
      beta-lactamases, and that it is a poor inducer of type I beta-lactamases,
      indicates that cefepime may be useful for treatment of infections resistant to
      earlier cephalosporins. In comparative trials, cefepime 1 to 2 g, usually
      administered intravenously twice daily, was as effective as ceftazidime 1 to 2 g,
      usually administered 3 times daily, for treatment of bacteraemia and infections
      of the lower respiratory tract, urinary tract, pelvis and skin and skin
      structures. Furthermore, cefepime was as effective as ceftazidime and
      piperacillin or mezlocillin in combination with gentamicin when administered as
      empirical treatment for fever in patients with neutropenia. A limited number of
      trials have found cefepime to be as effective as cefotaxime for the treatment of
      gynaecological and lower respiratory tract infections. Similarly, cefepime 2 g
      twice daily intravenously (alone or in combination with metronidazole) was as
      effective as gentamicin in combination with mezlocillin or clindamycin,
      respectively, for the treatment of intra-abdominal infection. Cefepime has a
      linear pharmacokinetic profile, an elimination half-life of approximately 2 hours
      and is primarily excreted by renal mechanisms as unchanged drug. Cefepime has a
      tolerability profile similar to that of other parenteral cephalosporins; adverse
      events are primarily gastrointestinal in nature. A total of 1.4 and 2.9% of
      patients receiving cefepime < or = 2 g/day and > 2 g/day, respectively, required
      treatment withdrawal as a result of any adverse event. Thus, cefepime has the
      advantage of an improved spectrum of antibacterial activity, and is less
      susceptible to hydrolysis by some beta-lactamases, compared with third generation
      cephalosporins. Despite these advantages, cefepime has not been found to be more
      effective than ceftazidime and cefotaxime in clinical trials, although most
      trials selected patients with organisms sensitive in vitro to both comparator
      agents. Further trials, particularly in areas of widespread bacterial resistance,
      are required to confirm the positioning of cefepime for treatment of serious
      infection, and in particular to further explore whether its potential advantages
      result in clinical benefits.

PMID- 7514971
TI  - The link between insulin resistance and hypertension. Effects of antihypertensive
      and antihyperlipidaemic drugs on insulin sensitivity.
AB  - Insulin resistance is generally interpreted as the physiological state under
      which insulin causes a reduced glucose-lowering effect. Hyperinsulinaemia is
      considered to be a result of insulin resistance. Many recent studies have
      suggested that hyperinsulinaemia and/or insulin resistance is associated with an
      elevated blood pressure, whereas several other studies have found a modest or no
      association. Many factors (e.g. adiposity, age, ethnic difference) have been
      suggested to confound the insulin-blood pressure relationship. Insulin is thought
      to raise blood pressure by a few possible mechanisms (e.g. stimulating
      sympathetic nervous system activity, enhancing renal tubular sodium
      reabsorption). On the other hand, insulin has also been reported to possess a
      vasodilatory property. Neither an insulin infusion within a physiological range
      nor continuously sustained hyperinsulinaemia in patients with insulinoma are
      associated with elevated blood pressure. Therefore, the relationship between
      insulin and blood pressure is still under discussion. Among the antihypertensive
      drugs, angiotensin converting enzyme (ACE) inhibitors seem to have marginal
      effects of improving insulin sensitivity, but whether this effect would lead to a
      better prognosis for diabetic patients remains to be proven. Lipid lowering drugs
      appear to show no benefit in lowering blood glucose.

PMID- 7514972
TI  - Omega-3 fatty acids. Current status in cardiovascular medicine.
AB  - Omega-3 polyunsaturated fatty acids (PUFA) reduce fasting and postprandial
      triglycerides, decrease platelet and leucocyte reactivity, and may slightly
      decrease blood pressure. Omega-3 PUFA may also beneficially influence vessel wall
      characteristics and blood rheology. Furthermore, these compounds have been shown
      to inhibit ventricular tachyarrhythmias in animals. Omega-3 PUFA may impair
      fibrinolysis and could lead to increased oxidation of lipoproteins. Potential
      adverse effects must not be neglected, but should be viewed in light of the
      beneficial effects of these agents. Clinical studies investigating the effects of
      dietary omega-3 PUFA in the prevention and treatment of cardiovascular disease
      (CVD) are beginning to emerge. The results have offered some promise, but further
      studies are needed to define the role of these agents in CVD. Long term trials
      and studies using omega-3 PUFA as adjuvants to conventional therapy in patients
      with coronary artery disease, hyperlipidaemia and hypertension may be of
      particular interest.

PMID- 7514977
TI  - Piperacillin/tazobactam. A review of its antibacterial activity, pharmacokinetic
      properties and therapeutic potential.
AB  - Combining tazobactam, a beta-lactamase inhibitor, with the ureidopenicillin,
      piperacillin, successfully restores the activity of piperacillin against beta
      lactamase-producing bacteria. Tazobactam has inhibitory activity, and therefore
      protects piperacillin against Richmond and Sykes types II, III, IV and V beta
      lactamases, staphylococcal penicillinase and extended-spectrum beta-lactamases.
      However, tazobactam has only species-specific activity against class I
      chromosomally-mediated enzymes. Resistant organisms include some Citrobacter
      spp., Enterobacter spp., Serratia spp., Xanthomonas maltophilia and Enterococcus
      faecium. Consistent with its in vitro activity, preliminary clinical data
      indicate that the fixed combination of piperacillin/tazobactam (dose ratio 8:1)
      is effective in the treatment of moderate to severe polymicrobial infections,
      including intra-abdominal, skin and soft-tissue and lower respiratory tract
      infections. In limited comparative trials, piperacillin/tazobactam demonstrated
      equivalent or better efficacy than standard comparator regimens in these
      infections. Piperacillin/tazobactam in combination with an aminoglycoside was
      effective in the empirical treatment of fever in patients with neutropenia and
      compared favourably with ceftazidime in combination with an aminoglycoside,
      although second-line therapy with a glycopeptide antibiotic may be indicated in
      unresponsive episodes. Data from phase III trials indicate that
      piperacillin/tazobactam has a tolerability profile typical of a penicillin agent.
      Piperacillin/tazobactam provides a broad spectrum of antibacterial activity in a
      convenient single formulation suitable for use in the treatment of polymicrobial
      infections. Possible limitations concern its restricted activity against class I
      beta-lactamases, enzymes that are becoming increasingly important in the
      nosocomial environment. Combined therapy with an aminoglycoside may be necessary
      in more serious infections.

PMID- 7514979
TI  - Reliability of EEG in the diagnosis of Creutzfeldt-Jakob disease.
AB  - Although EEG is generally considered a useful tool for the diagnosis of
      Creutzfeldt-Jakob disease (CJD), some cases have been reported where the EEG was
      non-specific. We reviewed a series of 15 CJD patients, observed in our institute
      in the period 1975-91. In 12 cases the diagnosis was confirmed on post-mortem
      examination. The prominent aspect of the present series was the homogeneity of
      clinical, neurophysiological and neuropathological data. All patients showed the
      presence of periodic sharp wave complexes (PSWC) and EEG reactivity to external
      stimuli or drugs was uniform. The EEG can give essential information for the
      diagnosis of CJD if 2 basic conditions are satisfied: (1) serial recordings are
      performed in relation to the different stages of the disease, and (2) not only
      the presence of PSWC is considered, but also the reactivity of EEG to dynamic
      events such as the response to external stimuli and drugs, and the level of
      consciousness.

PMID- 7514980
TI  - Brain-stem auditory evoked responses to hypercarbia in preterm infants.
AB  - To determine the effect of acute hypercarbia on brain-stem function in preterm
      neonates, we compared brain-stem auditory evoked responses (BAERs) during 8% CO2
      breathing to those elicited during room air breathing in 12 healthy preterm
      infants during the first week of life. End-tidal CO2 (ETpCO2), respiratory rate
      and depth were monitored throughout the protocol. Absolute wave latencies and
      interpeak intervals of the BAERs were analyzed from duplicate trials. During 8%
      CO2 breathing, ETpCO2, respiratory rate and depth of respiration increased
      significantly (P < 0.05). The absolute latency of wave V was prolonged (P <
      0.025) in the hypercarbic state as compared to baseline. Interpeak interval III-V
      was also prolonged (P < 0.025). Values of absolute peak latencies I and III were
      unaffected by the hypercarbic state. These data demonstrate that elevations in
      pCO2 which elicit ventilatory responses also effect the BAER. The specific
      effects on ventilatory pattern, peak V latency and interpeak interval III-V
      indicate brain-stem responsiveness and alterations in the more central components
      of the auditory pathway. These findings raise important considerations regarding
      the influence of hypercarbia on brain-stem function in preterm infants and the
      clinical management of such infants with abnormalities of gas exchange.

PMID- 7514983
TI  - Computer simulation of electrocortical activity at millimetric scale.
AB  - We report a simulation of electrocortical wave activity at millimetric scale,
      during the "desynchronised" state. Asymmetric sigmoid pulse/wave relations, short
      range excitatory/inhibitory interactions and long-range excitatory couplings of
      pools of cortical cells were modelled. Frequency/wave number analysis of cat
      electrocorticogram was compared with the results of simulation. Local standing
      waves, with wave numbers from about 0.25/mm to 3.3/mm independent of temporal
      frequency, appeared in real and simulated ECoG. These arise from interactions of
      excitatory and inhibitory cells and reciprocal excitation of pyramidal cells. The
      simulation also exhibits long wave length activity consistent with that of the
      real ECoG. Serial relay of excitation gives rise to travelling waves with a
      velocity of about 0.6 m/sec, which approximates earlier experimental estimates
      based on coherence. Interaction of the local and travelling waves results in
      group waves with high phase velocities (32 m/sec at 5 Hz, to 0.6 m/sec at 50 Hz).
      Such group waves have not yet been experimentally identified and would be readily
      confused with effects of volume conduction. However, the frequency response
      characteristics of the simulation, along with the group waves, may account for
      experimental findings of action potential correlation with local field potentials
      at 40-50 Hz and long-range synchronisation of action potentials.

PMID- 7514981
TI  - High resolution EEG: 124-channel recording, spatial deblurring and MRI
      integration methods.
AB  - This paper describes a method for increasing the spatial detail of the EEG and
      for integrating physiological data with anatomical models based on magnetic
      resonance images (MRIs). This method includes techniques to efficiently record
      EEG data from up to 124 channels, to measure 3-D electrode positions for
      alignment with MRI-derived head models, and to estimate potentials near the outer
      convexity of the cortex using a spatial deblurring technique which uses a
      realistic model of the structure of the head and which makes no assumptions about
      the number or type of generator sources. The validity of this approach has been
      initially tested by comparing estimated cortical potentials with those measured
      with subdural grid recordings from two neurosurgical patients. The method is
      illustrated with somatosensory steady-state evoked potential data recorded from 5
      healthy subjects. Results suggest that deblurred 124-channel topographic maps,
      registered with a subject's MRI and rendered in 3 dimensions, provide better
      spatial detail than has heretofore been obtained with scalp EEG recordings. The
      results also suggest that the potential for EEG as a functional neuroimaging
      modality has yet to be fully realized.

PMID- 7514984
TI  - A dry electrode for EEG recording.
AB  - This paper describes the design, fabrication and testing of a prototype dry
      surface electrode for EEG signal recording. The new dry electrode has the
      advantages of no need for skin preparation or conductive paste, potential for
      reduced sensitivity to motion artifacts and an enhanced signal-to-noise ratio.
      The electrode's sensing element is a 3 mm stainless steel disk which has a 2000 A
      (200 nm) thick nitride coating deposited onto one side. The back side of the disk
      is attached to an impedance converting amplifier. The prototype electrode was
      mounted on a copper plate attached to the scalp by a Velcro strap. The
      performance of this prototype dry electrode was compared to commercially
      available wet electrodes in 3 areas of electroencephalogram (EEG) recording: (1)
      spontaneous EEG, (2) sensory evoked potentials, and (3) cognitive evoked
      potentials. In addition to the raw EEG, the power spectra of the signals from
      both types of electrodes were also recorded. The results suggest that the dry
      electrode performs comparably to conventional electrodes for all types of EEG
      signal analysis. This new electrode may be useful for the production of high
      resolution surface maps of brain activity where a large number of electrodes or
      prolonged recording times are required.

PMID- 7514982
TI  - Dissociation between contingent negative variation and Bereitschaftspotential in
      a patient with cerebellar efferent lesion.
AB  - Contingent negative variation (CNV) and Bereitschaftspotential (BP) were from the
      scalp in a patient with a discrete infarct in the mesial tegmentum of the
      midbrain involving the decussation of the superior cerebellar peduncle.
      Bereitschaftspotential in association with hand movements was completely absent
      while CNV was normally present at the frontocentral midline. This indicates that
      CNV is, as opposed to BP, generated without cerebro-cerebellar interactivation,
      suggesting different generating mechanisms.

PMID- 7514985
TI  - All-night sleep EEG and artificial stochastic control signals have similar
      correlation dimensions.
AB  - EEG signals have been considered to be generated either by stochastic processes
      or by non-linear deterministic systems exhibiting chaotic behavior. To address
      this problem, the correlation dimension of the EEG was computed and compared to
      the correlation dimension of an artificial signal with identical power spectrum.
      By using a new type of personal super computer we were able for the first time to
      calculate the correlation dimension for the sleep episode of an entire night as
      well as for the corresponding artificial signal. The correlation dimension was
      high in episodes of rapid eye movement (REM) sleep, declined progressively within
      each non-REM sleep episode, and reached a low level at times when EEG slow waves
      (0.75-4.5 Hz) were dominant. The correlation dimension of the artificial signal
      and the EEG changed largely in parallel, although on average the values of the
      artificial signal were 7.3% higher. These results do not support the hypothesis
      that the sleep EEG is generated by a chaotic attractor.

PMID- 7514987
TI  - Long latency transient evoked potentials to rapid random stimulation: responses
      to single and multiple concurrent stimuli.
AB  - In EP testing, regular (periodic) stimulation at increasing rates produces
      progressive fusion of responses into steady-state wave forms. When stimuli are
      presented randomly in time this fusion does not occur. Medium and long latency
      transient EPs can be recorded to stimulation at interstimulus intervals which are
      much shorter than the EP wave form latencies. Individual transient EPs can be
      obtained to multiple independent stimuli presented concurrently when the stimuli
      are presented randomly to one another. The ability to obtain responses to rapid
      stimulation and to multiple independent stimuli provides opportunities for
      increased efficiency and complexity of testing, particularly involving long
      latency responses.

PMID- 7514986
TI  - Neuromonitoring during surgery--a comment.

PMID- 7514990
TI  - Evoked potentials recorded from the auditory cortex in man: evaluation and
      topography of the middle latency components.
AB  - The goal of this study is to determine and localize the generators of different
      components of middle latency auditory evoked potentials (MLAEPs) through
      intracerebral recording in auditory cortex in man (Heschl's gyrus and planum
      temporale). The present results show that the generators of components at 30, 50,
      60 and 75 msec latency are distributed medio-laterally along Heschl's gyrus. The
      30 msec component is generated in the dorso-postero-medial part of Heschl's gyrus
      (primary area) and the 50 msec component is generated laterally in the primary
      area. The generators of the later components (60-75 msec) are localized in the
      lateral part of Heschl's gyrus that forms the secondary areas. The localization
      of N100 generators is discussed.

PMID- 7514989
TI  - Recovery of hypoglycaemia-associated compromised cerebral function after a short
      interval of euglycaemia in insulin-dependent diabetic patients.
AB  - To test the hypothesis that compromised cerebral function, induced by recurrent
      hypoglycaemic episodes, may recover after a short interval of euglycaemia, we
      examined electrophysiological activity and symptom awareness during two
      sequential euglycaemic-hypoglycaemic clamp studies in 11 insulin-dependent
      diabetic patients without any signs of peripheral or autonomic neuropathy.
      Neurophysiological testing and evaluation of hypoglycaemic symptoms were
      performed at stable glycaemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol/l. The
      first clamp study was preceded by 3 short-term hypoglycaemic episodes, whereas
      the second clamp study followed a 2 day interval of strict euglycaemia. The
      latter caused a recovery of electrophysiological activity, which was demonstrated
      by recovery of delays of the middle latency auditory evoked potentials (latency
      shift of the P(a) component, MANOVA, P < 0.01). Reversal of hypoglycaemic symptom
      unawareness involved the overall symptom perception (MANOVA, P < 0.04), as well
      as the autonomic symptoms of heart pounding (P < 0.05) and sweating (P < 0.05).
      We conclude that the previously reported impaired cerebral function, occurring as
      a consequence of repetitive hypoglycaemic episodes, may recover after a single
      euglycaemic interval.

PMID- 7514991
TI  - Click-evoked responses from the cochlear nucleus: a study in human.
AB  - Recordings from the vicinity of the cochlear nucleus in 9 patients undergoing
      microvascular decompression operations to relieve hemifacial spasm, trigeminal
      neuralgia, tinnitus, and disabling positional vertigo were conducted by placing a
      monopolar electrode in the lateral recess of the fourth ventricle (through the
      foramen of Luschka), the floor of which is the dorsolateral surface of the dorsal
      cochlear nucleus. The click-evoked potentials recorded by such an electrode
      display a slow negative wave with a peak latency of about 6-7 msec on which
      several sharp peaks are superimposed. None of the peaks in the recordings from
      the vicinity of the cochlear nucleus coincided with any vertex-positive peaks of
      the brain-stem auditory evoked potentials. In recordings from the lateral aspect
      of the floor of the fourth ventricle near the cochlear nucleus 1 patient showed 2
      positive peaks, the earliest of which had a latency close to that of peak II and
      the second of which had a latency close to the negative peak between peaks III
      and IV of the brain-stem auditory evoked potentials. There is a distinct negative
      peak in the responses recorded from the midline of the floor of the fourth
      ventricle, the latency of which is only slightly shorter than that of peak V of
      the brain-stem auditory evoked potentials, supporting earlier findings that the
      sharp tip of peak V of the brain-stem auditory evoked potentials is generated by
      the termination of the lateral lemniscus in the inferior colliculus.

PMID- 7514978
TI  - Hyaluronic acid. A review of its pharmacology and use as a surgical aid in
      ophthalmology, and its therapeutic potential in joint disease and wound healing.
AB  - Hyaluronic acid is a naturally occurring polysaccharide with distinct
      physicochemical properties which underlie its application as a viscoelastic tool
      in ophthalmological surgery. In cataract surgery the role of hyaluronic acid in
      facilitating procedures and protecting the corneal endothelium is well
      established. Some benefit has also been gained with the use of hyaluronic acid in
      penetrating keratoplasty, trabeculectomy, retinal reattachment and trauma
      surgery, although its efficacy in these indications is less well-defined in the
      published literature. In addition to its lubricating and cushioning properties,
      demonstration of some in vitro anti-inflammatory activity and a possible disease
      modifying effect for hyaluronic acid in animals has prompted its investigation as
      a treatment in osteoarthritis and, to a much lesser extent, in rheumatoid
      arthritis. Hyaluronic acid 20 mg, as weekly intra-articular injections for 3 to 7
      weeks, improved knee pain and joint motion in patients with osteoarthritis.
      Although this occurred to a greater degree than with placebo in most comparisons,
      the effects of hyaluronic acid was similar to those of placebo in the largest
      trial. In the few available comparisons with other agents, hyaluronic acid
      appeared equivalent to methylprednisolone 40 mg (for 3 weeks) and to a single
      injection of triamcinolone 40 mg. Hyaluronic acid was distinguished from other
      therapies by providing a sustained effect after treatment discontinuation.
      Together with its very good tolerability profile, these properties justify
      further study of hyaluronic acid in patients with osteoarthritis. Some limited
      evidence of improvement in patients with rheumatoid arthritis, and a possible
      healing effect of hyaluronic acid on tympanic membrane perforations, represent
      additional areas of interest for future investigation. In summary, hyaluronic
      acid is a well-established adjunct to cataract surgery and may prove to be a
      promising option in the treatment of patients with osteoarthritis. Its very good
      tolerability provides further impetus for examination of its potential role in an
      extended scope of arthritic and ophthalmological indications, and in wound
      healing.

PMID- 7514988
TI  - Glossopharyngeal evoked potentials in normal subjects following mechanical
      stimulation of the anterior faucial pillar.
AB  - The anterior faucial pillar, which is innervated by the glossopharyngeal nerve,
      is thought to be important in eliciting the pharyngeal swallow in awake humans.
      Glossopharyngeal evoked potentials (GPEP), elicited by mechanically stimulating
      this structure, were recorded from 30 normal adults using standard averaging
      techniques and a recording montage of 16 scalp electrodes. Ten of the subjects
      experienced a desire to swallow in response to stimulation. Repeatable responses
      were recorded from all 30 subjects. The GPEPs recorded from the posterior scalp
      were W-shaped and consisted of P1, N1, P2, N2 and P3 peaks. Mean latencies of P1,
      N1 and P2 were 11, 16 and 22 msec, respectively, for both left and right pillar
      stimulation. In contrast, latencies of N2 and P3 varied significantly between
      left and right pillar stimulation. Mean latencies of N2 and P3 were 27 and 34
      msec for left, and 29 and 35 msec for right pillar stimulation. Topographical
      maps acquired at peak latencies for P1, N1 and P2 revealed consistent
      asymmetrical voltage distributions between the two hemispheres; the largest
      responses were recorded from the hemisphere ipsilateral to the side of
      stimulation. The scalp topography of N2 and P3 varied between male and female
      subjects as well as between left and right pillar stimulation. These findings
      support the hypothesis that mechanical stimulation to the anterior faucial pillar
      alone can elicit repeatable responses from the central nervous system. The
      integration of this subcortical/cortical activity with that of the medullary
      swallowing center may play an important role in eliciting the pharyngeal swallow.

PMID- 7514993
TI  - Dissociation of temporal and frontal components in the human auditory N1 wave: a
      scalp current density and dipole model analysis.
AB  - This study reports a combined scalp current density (SCD) and dipole model
      analysis of the N1 wave of the auditory event-related potentials evoked by 1 kHz
      tone bursts delivered every second. The SCD distributions revealed: (i) a sink
      and a source of current reversing in polarity at the inferotemporal level of each
      hemiscalp, compatible with neural generators in and around the supratemporal
      plane of the auditory cortex, as previously reported; and (ii) bilateral current
      sinks over frontal areas. Consistently, dynamic dipole model analysis showed that
      generators in and outside the auditory cortex are necessary to account for the
      observed current fields between 65 and 140 msec post stimulus. The frontal
      currents could originate from the motor cortex, the supplementary motor area
      and/or the cingulate gyrus. The dissociation of an exogenous, obligatory frontal
      component from the sensory-specific response in the auditory N1 suggests that
      parallel processes served by distinct neural systems are activated during
      acoustic stimulation. Implications for recent models of auditory processing are
      discussed.

PMID- 7514992
TI  - Visual and somatosensory event-related brain potentials in autistic children and
      three different control groups.
AB  - Event-related potentials (ERPs) to visual and somatosensory stimuli, generated
      during an oddball task, were obtained in a group of autistic children and 3
      control groups (normal, attention-deficit, and dyslectic children, respectively).
      The task included the presentation of standard, deviant, and novel stimuli and
      had a (between-group) passive vs. active (counting) condition. Research questions
      were whether (a) autistic children differ from other children with respect to the
      processing of visual and/or somatosensory stimuli, as measured in the amplitude
      of the N1, mismatch activity, and P3, (b) autistic children specifically have
      problems in the processing of distal (visual) stimuli, compared to the processing
      of proximal (somatosensory) stimuli, and (c) autistic children have an atypical
      lateralization pattern of ERP activity. Only in the autistic group a task effect
      on the visual P2N2 (mismatch activity) and larger P3s to novels than to deviants
      were found, in both the visual and the somatosensory modality. There also was a
      smaller occipital P3 to visual standard stimuli in the passive condition in the
      autistic group than in 2 control groups. We concluded that autistics (a) differ
      from several other groups of children with respect to the visual P2N2 and the
      visual and somatosensory P3, (b) show abnormalities in the processing of both
      proximal and distal stimuli, and (c) show no indication of abnormal
      lateralization of ERPs.

PMID- 7514994
TI  - P300 from a single auditory stimulus.
AB  - The P3(00) event-related brain potential (ERP) was elicited with auditory stimuli
      to compare 2 different discrimination tasks. The oddball paradigm presented both
      target and standard tones; the single-stimulus paradigm presented a target but no
      standard tone stimulus. Experiment 1 manipulated target stimulus probability
      (0.20, 0.50, 0.80) and produced highly similar P3 amplitude and latency results
      across probability levels for each paradigm. Experiment 2 factorially varied
      inter-stimulus interval (2 sec, 6 sec) and target stimulus probability (0.20,
      0.80). P3 amplitude and latency were highly similar for both the oddball and
      single-stimulus procedures across all conditions.

PMID- 7514995
TI  - The magnetic counterpart of the contingent negative variation.
AB  - The magnetic counterpart of the CNV, the contingent magnetic variation (CMV), was
      investigated in an Go/No Go design: subjects moved their index finger to the
      offset of a 4 sec tone of a certain frequency in the Go condition and were asked
      not to move during presentation of a 4 sec tone of different frequency in the No
      Go condition. During the preparatory interval, both the CMV and the electrical
      wave form followed a similar time course and both produced an equally pronounced
      statistical difference between conditions (Go and No Go). Compared to the
      variability in the auditory evoked fields, the CMV showed considerably more
      variance in the field distribution across subjects. The polarity reversal across
      the temporal surface of the head and the pronounced amplitudes over inferior
      temporal areas led us to conclude that a significant temporal activity
      contributes to both the late and the early CMV. However, neither for the early
      nor for the late CMV component did a single equivalent dipole prove to be a
      satisfying model. The data are consistent with the suggestion that the earlier as
      well as the later aspects of the CMV are fed through distributed sources in
      motoric, sensory and association areas, a distribution with considerable
      intersubject variability.

PMID- 7514996
TI  - Tyrosine kinase inhibitor AG18 arrests follicle-stimulating hormone-induced
      granulosa cell differentiation: use of reverse transcriptase-polymerase chain
      reaction assay for multiple messenger ribonucleic acids.
AB  - A sensitive assay of multiple mRNAs by reverse transcriptase-polymerase chain
      reaction was adopted to study the hormonally regulated expression of
      steroidogenic enzymes in primary rat granulosa cells in culture. As little as 15
      60 ng total RNA prepared from cultured cells were reverse transcribed in the
      presence of pd(T)6, and polymerase chain reaction was conducted in the presence
      of specific oligonucleotide pairs designed to identify cDNAs of steroidogenic
      enzymes. In combination with Northern blot analysis of cholesterol side-chain
      cleavage cytochrome P450 (P450scc) message, it is shown that a novel protein
      kinase inhibitor, tyrphostin AG18, arrests the FSH-induced accumulation of
      P450scc mRNA. This inhibition is dose dependent (IC50, 15 microM) and reversible.
      The addition of 80 microM AG18 to cells containing high levels of P450scc mRNA
      caused a rapid decline of the cytochrome message (t 1/2, 5 h), similar to the
      effect of 30 micrograms/ml alpha-amanitin. However, concomitant addition of the
      two drugs did not accelerate the mRNA degradation process, suggesting that AG18
      does not affect message stabilization. Tyrphostin AG18 did not affect mRNA
      species that are not FSH inducible, such as the ribosomal protein L19, or the
      constitutively expressed low levels of steroid 5 alpha-reductase mRNA. Moreover,
      even the extremely high levels of P450scc mRNA in granulosa-lutein cells, being
      cAMP independent and terminally differentiated a few hours after LH surge, were
      not affected by the addition of AG18 in culture. In contrast, two additional key
      and FSH-inducible steroidogenic enzymes, i.e. aromatase cytochrome P450 and 3
      beta-hydroxysteroid dehydrogenase-I, were inhibited by AG18 at their mRNA levels.
      These results suggest that an as yet undetermined tyrosine kinase pathway is
      involved in the cAMP-dependent signal transduction pathway of FSH action, so that
      the presence of AG18 does not allow FSH induction of gene expression to occur.

PMID- 7514997
TI  - Expression of high density lipoprotein-binding protein messenger ribonucleic acid
      in the rat ovary and its regulation by gonadotropin.
AB  - The presence of high density lipoprotein-binding protein (HBP) mRNA in rat
      ovarian cells and its possible regulation by gonadotropin were examined in this
      study. RNA, isolated from pseudopregnant rat ovaries, was amplified by reverse
      transcriptase-polymerase chain reaction (PCR) with HBP-specific oligonucleotide
      primers. A distinct and prominent 576-basepair PCR product was generated.
      Sequence analysis revealed that the sequence homology of the PCR product and the
      corresponding human HBP cDNA sequence was greater than 90%. Using Northern blot
      analysis, we identified two species of HBP mRNA transcripts in the ovarian cells
      (i.e. a major one of 4.5 kilobases and a minor one of 6.0 kilobases). Cellular
      localization of HBP mRNA in the ovary was determined by in situ hybridization
      analysis. Prominent specific hybridization of the labeled antisense probe was
      observed in all cell types of the follicles and corpora lutea, whereas little
      hybridization was observed in the stroma and the connective tissues separating
      corpora lutea and follicles. As hCG has been shown to induce high density
      lipoprotein-binding activity in the rat ovary, we examined the possible
      regulation of ovarian HBP mRNA by this hormone. Administration of hCG caused a
      significant time-dependent increase in the steady state levels of HBP mRNA. The
      induction of HBP mRNA levels by hCG is specific for the ovary, as pretreatment
      with hCG had no effect on the HBP mRNA levels of the liver, heart, lung, or
      kidney. The present study, for the first time, shows conclusively the presence of
      HBP mRNA in the rat ovary and its induction by hCG, implicating a physiological
      role for HBP in the ovary.

PMID- 7514998
TI  - Complex formation by human insulin-like growth factor-binding protein-3 and human
      acid-labile subunit in growth hormone-deficient rats.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3), after first associating
      with IGF-I or IGF-II, is able to associate with the acid-labile subunit (ALS) and
      form a 140-kDa complex. To investigate the factors regulating ternary complex
      formation in vivo, human (h) IGFBP-3, hIGF-I, and hALS were administered in
      various combinations to GH-deficient (dw/dw) rats. hIGFBP-3 had a complex pattern
      of disappearance from the rat circulation, with an initial phase lasting minutes
      and a prolonged phase(s) lasting hours. If coinjected with hIGF-I, significantly
      more hIGFBP-3 was retained over 2 h. The molecular distribution of hIGFBP-3 was
      determined after size-separation chromatography. After an iv bolus of hIGFBP-3,
      36.1 +/- 5.0% was in the 140-kilodalton complex at 5 min; this increased to 55.1
      +/- 7.1% if hIGF-I was coinjected (P < 0.05). The 140-kDa complex disappeared
      slowly over hours, whereas 50- and 30-kDa forms of hIGFBP-3 cleared rapidly, with
      half-lives of minutes. To determine the importance of ALS in regulating the
      molecular distribution of hIGFBP-3, hALS was coinjected. Immunoreactive hALS
      disappeared slowly from the circulation and was shown to retain functional
      activity after 2 h in vivo. Coadministration of hALS did not influence the
      pattern of ternary complex formation, consistent with the presence of excess
      endogenous rat ALS. We conclude that ALS circulates in excess even in GH
      deficiency, is retained in the circulation for hours, and determines the
      stability of the 140-kDa complex, whereas IGF-I is a limiting factor in ternary
      complex formation by hIGFBP-3.

PMID- 7514999
TI  - Regulation of human chorionic gonadotropin secretion and messenger ribonucleic
      acid levels by follistatin in the NUCC-3 choriocarcinoma cell line.
AB  - In this study, the NUCC-3 choriocarcinoma cell line was used as an in vitro
      placental cell model to investigate the effects of follistatin on basal and GnRH
      stimulated hCG secretion and/or its subunit mRNA levels. Follistatin (1.5-100
      ng/ml; 48 h) alone did not affect basal hCG secretion or its subunit mRNA levels.
      GnRH increased hCG secretion and hCG beta-subunit mRNA levels in a dose-dependent
      manner, with maximal effects (2.37- and 2.4-fold increases, respectively) at a
      dose of 10(-8) M after 24 h of culture (P < 0.001). The time-course study showed
      that the increase in hCG secretion induced by GnRH occurred between 6-48 h after
      treatment. Follistatin (6-100 ng/ml; 48 h) significantly suppressed GnRH
      stimulated hCG secretion and hCG alpha- and beta-subunit mRNA levels, with
      maximal suppression of 73.1%, 106.9%, and 129.1%, respectively (P < 0.001). In
      addition, follistatin (25 ng/ml) inhibited hCG secretion in response to phorbol
      12-myristate 13-acetate (100 nM) by 90.3%. However, follistatin had no effect on
      hCG secretion evoked by forskolin (10 microM), and no change in hCG secretion was
      observed after treatment with a calcium ionophore (A23187; 10 microM) alone or in
      combination with follistatin. Furthermore, there was no significant difference in
      the half-lives of hCG alpha and -beta mRNA induced by GnRH alone compared with
      those induced by GnRH plus follistatin (P > 0.1), indicating that follistatin did
      not affect the stability of hCG alpha and -beta mRNA. Our data suggest that
      follistatin inhibits GnRH-stimulated hCG secretion as well as hCG alpha- and beta
      subunit mRNA levels in the NUCC-3 choriocarcinoma cell line by decreasing the
      rate of transcription through the second messenger transduction system-protein
      kinase-C, rather than by affecting the stability of mRNA. These findings indicate
      that follistatin may play an important role in the regulation of hCG production
      in the placenta during pregnancy.

PMID- 7515002
TI  - Cellular localization and regulation of gene expression for components of the
      insulin-like growth factor ternary binding protein complex.
AB  - Insulin-like growth factors (IGFs) are present in the circulation, largely as
      part of a high mol wt complex including IGF-binding protein-3 (IGFBP-3) and an
      acid-labile subunit (ALS). This study used in situ hybridization to investigate
      the cellular sites of synthesis of these factors in the rat and to evaluate
      changes in transcript levels during development and after hypophysectomy and GH
      treatment. IGFBP-3 transcripts are considerably more abundant and widely
      expressed than ALS at birth, but both are present in liver and kidney. Hepatic
      IGFBP-3 gene expression increases slightly, whereas ALS increases dramatically in
      the first few weeks after birth. IGFBP-3 mRNA is concentrated in portal venous
      and sinusoidal endothelium, but is not detected in hepatocytes, whereas ALS mRNA
      is diffusely expressed by hepatocytes, but is not detected in nonparenchymal
      cells. Both transcripts are localized in the renal cortex; however, IGFBP-3 mRNA
      is concentrated in interstitial cells, whereas ALS is expressed in proximal
      tubule epithelium. Hypophysectomy results in a 90% reduction in hepatic ALS and
      an approximately 50% decrease in IGFBP-3 mRNA level. ALS, but not IGFBP-3,
      transcripts were also reduced in the kidney. GH receptor mRNA is coexpressed with
      ALS in liver and kidney, suggesting that the effects of GH on ALS gene expression
      may be direct. In summary, the fact that IGFBP-3 gene expression is far more
      widespread than that of ALS in both spatial and temporal parameters suggests that
      IGFBP-3 has a role apart from contribution to the ternary complex. We have also
      shown that IGFBP-3 and ALS are synthesized by distinct hepatic cell types in an
      anatomical organization that may serve to ensure efficient formation of the
      ternary complex in the blood passing through the sinusoids. Finally, the present
      data suggest that regulation of ALS synthesis may be the primary site of GH
      regulation of ternary complex formation.

PMID- 7515001
TI  - Gonadotropin-releasing hormone stimulates glycoprotein hormone alpha-subunit
      messenger ribonucleic acid (mRNA) levels in alpha T3 cells by increasing
      transcription and mRNA stability.
AB  - Pulsatile GnRH stimulates gonadotropin secretion, whereas continuous exposure to
      GnRH causes pituitary desensitization and suppressed levels of LH and FSH. At the
      level of gene expression, continuous GnRH also causes partial or complete
      suppression of the LH beta and FSH beta genes, but expression of the alpha
      subunit gene is stimulated without evidence of desensitization. In this report,
      we examined the transcriptional and posttranscriptional mechanisms by which GnRH
      controls alpha-gene expression using the gonadotrope-derived alpha T3 cell line.
      Continuous GnRH caused a 4- to 5-fold accumulation of alpha mRNA over 72 h,
      without evidence of a decline. In contrast, measurements of alpha-gene
      transcription, either by nuclear run-on assays or using a stably integrated alpha
      LUC reporter gene, revealed that GnRH caused a transient increase in alpha
      promoter activity, followed by a decline after 4-6 h. The prolonged accumulation
      of alpha mRNA at a time when transcriptional activity had abated was accounted
      for by independent effects of GnRH on alpha mRNA stability. After prior treatment
      with GnRH, its removal either by washout or using a GnRH receptor antagonist
      caused an abrupt decline in steady state alpha mRNA levels (t1/2, < 2 h).
      Readdition of GnRH prevented the decay in alpha mRNA, and experiments using the
      transcriptional inhibitor actinomycin-D confirmed that this effect of GnRH did
      not require transcription. Consistent with these results, pulse-chase analyses of
      mRNA stability demonstrated that GnRH increased the alpha mRNA half-life 6.7
      fold, from 1.2 h in the absence of GnRH to 8.0 h in the presence of GnRH. We
      conclude that GnRH induces a transient burst of alpha-gene transcription that is
      accompanied by marked induction of mRNA stability.

PMID- 7515000
TI  - Detection of placental growth hormone variant and chorionic somatomammotropin
      ribonucleic acid expression in human trophoblastic neoplasms by reverse
      transcriptase-polymerase chain reaction.
AB  - Attempts to assess human placental GH variant (hGH-V) and chorionic
      somatomammotropin (hCS) RNA in choriocarcinoma cell lines have been hampered by
      low levels of expression and limited sensitivity of RNA blotting analysis. We
      examined human choriocarcinoma BeWo, JAR, and JEG-3 cell lines as well as samples
      of complete hydatidiform moles for expression of members of the human GH (hGH)
      gene family using reverse transcriptase-polymerase chain reaction. A single and
      common set of primers was designed and used to detect products of the hGH/hCS
      genes as well as distinguish processed RNA from any contaminating DNA.
      Transcripts from the hCS genes hCS-A and -B were distinguished from placental hGH
      variant (hGH-V) and hCS-like (hCS-L) gene RNA by diagnostic restriction digestion
      of the polymerase chain reaction products. The expected pattern of hGH/hCS RNA
      expression was detected in term placenta, where hCS and hGH-V/hCS-L transcripts
      represented approximately 95% and approximately 5% of the total hGH/hCS RNA,
      respectively. The level of hCS RNA varied from 22-99% of the total hGH/hCS RNA in
      the neoplastic trophoblast samples, and variable levels of hGH-V and hCS-L RNA
      were also observed. In choriocarcinoma JAR cells, hGH-V RNA represented
      approximately 78% of the total hGH/hCS RNA compared to approximately 22% for hCS.
      Further, although low hCS-L RNA levels (< 1%) were found in term placenta and two
      of the hydatidiform moles, hCS-L transcripts represented 11% of the total hGH/hCS
      RNA in a third hydatidiform mole. Finally, in contrast to the detection of
      variable levels of hCS-L RNA in term placenta and hydatidiform mole samples, no
      hCS-L transcripts were detected in the three choriocarcinoma cell lines examined.
      These patterns reflect either deregulated hGH/hCS gene expression in neoplastic
      trophoblasts or differences that accompany the process of differentiation of
      trophoblast subpopulations. Regardless, this suggests that the control of hGH-V
      and hCS-L gene expression is distinct from that of the hCS-A and hCS-B genes and
      raises questions about the possible involvement of hGH/hCS family members in the
      pathology of placental abnormalities.

PMID- 7515003
TI  - Characterization of rat serum insulin-like growth factor-binding proteins by two
      dimensional gel electrophoresis: identification of a potentially novel form.
AB  - The insulin-like growth factor-binding proteins (IGFBPs) in rat serum were
      analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis followed by Western ligand or immunoblotting. A ligand blot of
      adult female rat serum revealed at least 20 proteins that bound labeled IGF-I
      specifically. They ranged in size from about 24-50K, and their pI values ranged
      from approximately 5.5-8.0. Immuno- and ligand blots showed that IGFBP-3 appeared
      as a broad band composed of numerous individual spots of about 40-45K, with pI
      values ranging from about 5.5-7.7. Immunoblots showed that IGFBP-4 resolved into
      at least three spots of approximately 29K, with pI values of about 6.3-6.7 and an
      approximately 24K nonglycosylated form that usually appeared as a single spot
      with a pI of about 7, but occasionally it resolved into a doublet. Immunoblots of
      neonatal rat serum using antiserum to IGFBP-2 resulted in immunoreactivity of two
      sets of proteins: approximately 33K forms composed of two proteins and
      approximately 30K forms comprising at least five different variants with pI
      values of about 7.0-7.5. However, ligand analysis showed that only the 30K forms
      had binding activity. IGFBP-1, -5, and -6 were not detectable by immunoblotting.
      However, a set of about 29K IGFBPs with pI values of approximately 5.9, which
      appears in significant amounts in the serum of pups and diabetic rats and in
      placental tissue-conditioned medium, has been tentatively identified as IGFBP-1
      by ligand blotting. One finding of particular interest is an approximately 50K BP
      with a pI of about 6 that comigrates with IGFBP-3. However, unlike IGFBP-3, which
      is glycosylated and undergoes proteolysis during gestation, this approximately
      50K IGFBP is not susceptible to endoglycosidase-F treatment and persists
      throughout pregnancy. Immunoblotting analysis revealed weak cross-reactivity
      between the approximately 50K IGFBP and antiserum to IGFBP-4. These results show
      that the rat serum IGFBPs are more heterogeneous than was previously realized.
      The two-dimensional system will allow changes in these different forms to be
      evaluated critically in different physiological and experimental states.

PMID- 7515004
TI  - Characterization of K+ and Ca2+ ionic currents in glomerulosa cells from human
      adrenal glands.
AB  - Ionic currents of primary cultured glomerulosa cells from human adrenal glands
      were studied with the patch-clamp technique. Two types of outward K+ currents and
      two types of inward Ca2+ currents were described. The transient outward K+
      current activated at potential positive to -40 mV and demonstrated a marked time
      dependent inactivation. It was blocked by 4-aminopyridine but not
      tetraethylammonium. A second type of outward current activated rapidly at the
      depolarization onset and then increased slowly with no time-dependent
      inactivation. The transient inward T-type Ca2+ current was activated for
      potential positive to -60 mV with a maximal current amplitude at -30 mV and zero
      current voltage at +40 mV; it was completely inactivated for membrane potential
      positive to -40 mV. The pharmacological studies of the T-type channel showed that
      Ni2+ was a potent blocker but that the channel was not sensitive to
      dihydropyridine. The long-lasting inward Ca2+ current was activated for
      potentials positive to -20 mV with a maximum current amplitude at +70 mV. This
      current was increased by the agonist Bay K 8644 and blocked by the antagonist
      nifedipine; in addition, it was blocked by Cd2+ but less sensitive to Ni2+. This
      study revealed that glomerulosa cells from human adrenal demonstrated the
      presence of K+ and Ca2+ currents similar to those found in rat and bovine cells.
      Moreover, the main stimuli of aldosterone secretion, ACTH and angiotensin II,
      induce an increase in aldosterone secretion which is inhibited in a Ca(2+)-free
      external medium.

PMID- 7515006
TI  - Preservation of glucose-responsive islet beta-cells during serum-free culture.
AB  - This study describes a serum-free medium in which adult rat islet beta-cells can
      be cultured in suspension for at least 9 days without a detectable loss in cell
      number or function. The medium is composed of Ham's F-10 with 10 mM glucose, 1%
      BSA, and 50 microM isobutylmethylxanthine. After 9 days of culture, beta-cell
      aggregates had preserved their initial DNA content, with more than 80%
      ultrastructurally intact cells. Their rates of glucose-inducible insulin
      synthesis (64 +/- 13 fmol/10(3) cells.2 h) and release (173 +/- 44 fmol/10(3)
      cells.2 h) were comparable to those previously determined in overnight cultured
      beta-cells. Their secretory response to 20 mM glucose plus 10(-8) M glucagon was
      biphasic and 10-fold elevated above the basal level. Their secretory and
      biosynthetic activities at basal (1.25 mM) glucose levels were significantly
      higher than after culture with serum. These elevated basal activities are
      attributed to a rise in the proportion of beta-cells with high content in pale
      secretory granules. Supplementing the serum-free medium with GH (1 micrograms/ml)
      plus glucagon (10(-8) M) further increased basal activities, leading to cellular
      degranulation and reduced hormone release after stimulation. Control cultures in
      Ham's F-10 with 10 mM glucose and 10% fetal calf serum reduced the initial DNA
      content by 40% and, consequently, the total amount of hormone synthesis and
      release. Surviving cells exhibited a lower secretory responsiveness than those
      recovered from serum-free medium; their lower basal activities coincided with an
      absence of cells with high content in pale granules. It is concluded that
      preservation of glucose-responsive beta-cells during suspension culture requires
      conditions that keep the cells recruited into glucose-dependent functions. Such a
      condition is achieved by the presently defined serum-free medium. It is
      characterized by the presence of a subpopulation of beta-cells with a high
      proportion of pale secretory granules.

PMID- 7515005
TI  - Pituitary adenylate cyclase-activating polypeptide effects in pituitary cells:
      modulation by gonadotropin-releasing hormone in alpha T3-1 cells.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) acts via type I
      receptors in the pituitary to stimulate cAMP production. Gonadotropes are likely
      target cells for PACAP action, and we have recently shown alpha T3-1 cells, a
      clonal gonadotrope-derived cell line, to be PACAP responsive. Here we have
      explored the influence of GnRH on PACAP action in alpha T3-1 cells and show that
      PACAP38-stimulated cAMP production is inhibited by GnRH in both the presence and
      the absence of a phosphodiesterase inhibitor. This effect appears not to be Ca++
      mediated but is mimicked by protein kinase C activation with phorbol 12-myristate
      13-acetate. However, GnRH and phorbol 12-myristate 13-acetate do not inhibit
      binding of [125I]PACAP27 to intact alpha T3-1 cells, nor do they inhibit
      forskolin- or cholera toxin-stimulated cAMP accumulation, implying that the
      inhibitory effects are exerted at early stages in the PACAP receptor signaling
      pathway but distal to receptor occupancy. When cells were preincubated with
      PACAP38, extensive washing failed to prevent the stimulatory effect of the
      polypeptide presumably because of the slow rate of receptor-ligand dissociation.
      However, when the time course of PACAP38-stimulated effects on intracellular cAMP
      was assessed, the stimulatory effect of PACAP38 could be rapidly reversed by GnRH
      addition, and the inhibitory effect of GnRH was rapidly be reversed by a GnRH
      receptor antagonist. The data provide the first demonstration of cross-talk
      between phospholipase C and adenylate cyclase-activating peptides in gonadotrope
      derived cells and establish the potential for hormonal modulation of PACAP
      action. We suggest that this inhibitory effect of GnRH might enable the releasing
      hormone to control the kinetics of cAMP signaling in gonadotropes in vivo.

PMID- 7515007
TI  - Human milk contains granulocyte colony stimulating factor.
AB  - Human milk provides the neonate with a variety of balanced nutrients and contains
      biologically active molecules such as hormones and growth factors. We have
      utilized a sensitive enzyme immunoassay to detect the granulocyte stimulator,
      granulocyte colony-stimulating factor (G-CSF) in human milk samples. The 12 milk
      samples tested contained G-CSF ranging from 45 to 1551 pg/ml.

PMID- 7515009
TI  - The islet-acinar axis of the pancreas: is there a role for glucagon or a glucagon
      like peptide?
AB  - Intravenous glucagon inhibits exocrine pancreatic secretion in vivo, but
      exogenous glucagon does not affect exocrine secretion in vitro. Recent work,
      however, suggested that endogenous glucagon may be involved in the regulation of
      exocrine secretion even in vitro. We therefore investigated the effects of
      exogenous and endogenous glucagon on exocrine secretion by the isolated perfused
      rat pancreas in the presence of 1.8 mM glucose. Exogenous glucagon did not affect
      CCK-stimulated amylase output. 20 mM arginine stimulated glucagon release, but
      did not affect basal enzyme secretion. CCK-stimulated amylase output, however,
      was significantly inhibited in the presence of arginine. This inhibitory effect
      of arginine on exocrine pancreatic secretion could be blocked by glucagon
      antibodies, but not by nonspecific gammaglobulins. Thus exogenous glucagon failed
      to affect exocrine pancreatic secretion in vitro, but endogenously released
      glucagon or a glucagon-like peptide inhibited amylase release in the isolated
      perfused pancreas. We conclude that glucagon or a glucagon-like peptide may be a
      mediator in the islet-acinar axis.

PMID- 7515008
TI  - The 5' end of yeast 5.8S rRNA is generated by exonucleases from an upstream
      cleavage site.
AB  - We have developed techniques for the detailed analysis of cis-acting sequences in
      the pre-rRNA of Saccharomyces cerevisiae and used these to study the processing
      of internal transcribed spacer 1 (ITS1) leading to the synthesis of 5.8S rRNA. As
      is the case for many eukaryotes, the 5' end of yeast 5.8S rRNA is heterogeneous;
      we designate the major, short form 5.8S(S), and the minor form (which is seven or
      eight nucleotides longer) 5.8S(L). These RNAs do not have a precursor/product
      relationship, but result from the use of alternative processing pathways. In the
      major pathway, a previously unidentified processing site in ITS1, designated A3,
      is cleaved. A 10 nucleotide deletion at site A3 strongly inhibits processing of
      A3 and the synthesis of 5.8S(S); processing is predominantly transferred to the
      alternative 5.8S(L) pathway. Site A3 lies 76 nucleotides 5' to the end of
      5.8S(S), and acts as an entry site for 5'-->3' exonuclease digestion which
      generates the 5' end of 5.8S(S). This pathway is inhibited in strains mutant for
      XRN1p and RAT1p. Both of these proteins have been reported to have 5'-->3'
      exonuclease activity in vitro. Formation of 5.8S(L) is increased by mutations at
      A3 in cis or in RAT1p and XRN1p in trans, and is kinetically faster than 5.8S(S)
      synthesis.

PMID- 7515010
TI  - Differential removal of insulin-like growth factor binding proteins in rat serum
      by solvent extraction procedures.
AB  - Solvent extraction of serum and other biological fluids at an acidic pH is a
      convenient method to remove the insulin-like growth factor binding proteins
      (IGFBPs); however, an incomplete removal of IGFBPs can occur and this can
      potentially interfere with the radioimmunoassay of insulin-like growth factors
      (IGFs). This study compared the removal of IGFBPs from normal adult rat serum and
      5-day old neonatal rat serum by acid-gel filtration, and three solvent extraction
      methods, i.e., acid-ethanol (AE), acid-cryo-ethanol (ACE) and formic acid-acetone
      (FAA) treatments by western ligand blotting and slot-blotting analysis. In adult
      rat serum all three extraction methods removed nearly 75% of total IGFBPs
      present. For the neonatal serum, AE and FAA were very inefficient in eliminating
      the IGFBPs, while ACE was somewhat better, as it removed nearly 30% of IGFBPs.
      Ligand blots of extracted samples showed that IGFBPs of lower size range, 24 to
      32 kDa (IGFBP-4, IGFBPs-1 and -2), were resistant to solvent extraction. Acid-gel
      filtration, in contrast, eliminated > 95% of IGF-binding components in both sera.
      Determination of IGF-I concentrations in samples after gel filtration and
      extraction methods revealed lower IGF-I values in neonatal serum in acid
      extracted samples. These data caution against using solvent extractions for IGFBP
      removal in fetal/neonatal serum.

PMID- 7515015
TI  - Molecular cloning of complementary deoxyribonucleic acids for the pituitary
      glycoprotein hormone alpha-subunit and luteinizing hormone beta-subunit precursor
      molecules of Japanese quail (Coturnix coturnix japonica).
AB  - Complementary DNAs encoding precursor molecules of the pituitary glycoprotein
      hormone (PGH) alpha- and luteinizing hormone (LH) beta-subunits of Japanese quail
      were isolated from a quail adenohypophyseal cDNA library using corresponding
      chicken cDNAs as hybridization probes. The isolated cDNAs had a length of 695 and
      724 bp, respectively, and contained sequences of 5' and 3' untranslated regions
      and an entire coding region of the precursor molecules. Two series of
      incompletely repeating and partially overlapping nucleotide sequences were
      observed over a part near the 3' end of the apoprotein coding region and the 3'
      untranslated region in the beta-subunit cDNA. One of them consisted of two
      repeated sets of 71 bases and the other consisted of six repeated sets of 30
      bases or less. The predicted amino acid sequence showed that signal peptide and
      apoprotein of the alpha-subunit consisted of 24 and 96 amino acid residues,
      respectively, and those of the beta-subunit consisted of 47 and 119 amino acid
      residues, respectively. Hybridization of the quail PGH alpha- and LH beta-subunit
      cDNAs to adenohypophyseal RNA showed that sizes of PGH alpha- and LH beta-subunit
      precursor mRNAs were about 1.1 and 0.9 kb, respectively. Amounts of both mRNAs
      were increased three to four times by castration in male quail. A comparison of
      the amino acid sequences of each of the PGH alpha- and LH beta-subunit precursors
      of the quail and other vertebrates indicated that the apoprotein, especially that
      of the alpha-subunit, was conserved (59 to 85% and 34 to 55% homology in the
      alpha- and beta-subunits, respectively), while the signal peptide was diversified
      (4 to 75% and 4 to 45% homology in the alpha- and beta-subunits, respectively).
      In the LH beta-subunit apoprotein, interclass homology values varied in a narrow
      range and did not show a clear relation with the phylogenic distance, while
      interclass homology values in the alpha-subunit apoprotein and both signal
      peptides reflected the phylogenic distance. This characteristic feature of the LH
      beta apoprotein can be explained by assuming that the variable portion of the LH
      beta apoprotein molecule evolved with a higher speed than that of the other
      peptides, and consequently no sequence common with other classes remained. This
      highly variable sequence may be responsible for the high animal-class specificity
      of the interaction between LH and its receptor.

PMID- 7515014
TI  - The neurosecretory staining in the cerebral ganglia of the Japanese abalone
      (ezoawabi), Haliotis discus hannai, and its relationship to reproduction.
AB  - Neurosecretory staining in the cerebral ganglia of the Japanese abalone
      (ezoawabi), Haliotis discus hannai, was studied during the reproductive cycle.
      The variation in stain affinity of the cells and the amount of neurosecretory
      material contained in the cells were measured during the study. Four cell types
      were found in the cerebral ganglion. Neurosecretory activity was found in Cell
      Types A and B, and the amount of neurosecretory material in the cells and the
      stain intensity of cellular material varied with the reproductive cycle. Cell
      Types C and D were not neurosecretory. The stain intensity of Cell Type A showed
      a correlation with vitellogenesis in the ovary. The stain intensity of Cell Type
      A in males showed no apparent correlation with gonad development or maturation.
      Cell Type B in both sexes did not show a correlation with gametogenesis,
      vitellogenesis, or spawning.

PMID- 7515016
TI  - Three selectable markers for transformation of Ustilago maydis.
AB  - Although Ustilago maydis is readily amenable to molecular genetic
      experimentation, few antibiotic-resistance markers are available for DNA-mediated
      transformation. This poses constraints on experiments involving targeted gene
      disruption and complementation. To address this problem, we constructed vectors
      using one of three additional genes as dominant selectable markers for
      transformation. Two genes, sat-1 (encoding streptothricin acetyltransferase) and
      Sh-ble (encoding a phleomycin-resistance polypeptide), are of bacterial origin
      and have been engineered for expression in Ustilago sp. The third gene encodes an
      allele of U. maydis beta-tubulin that confers resistance to the fungicide
      benomyl.

PMID- 7515017
TI  - Sequence and expression of a cDNA encoding the mouse homologue of the rat
      ribosomal protein L28.
AB  - A cDNA encoding the mouse homologue of the rat ribosomal protein L28 was isolated
      from an adult mouse total testis cDNA library. The L28 cDNA contained a single
      long open reading frame and exhibited a high degree of conservation to rat L28 at
      both the nucleotide and amino-acid levels. Northern blot hybridization analysis
      detected a single transcript in embryo, placenta and adult tissues.

PMID- 7515011
TI  - Comparison of protein synthesis profiles in chronic lymphocytic leukaemia cells
      and B-lymphocytes from peripheral blood, cord blood and tonsil.
AB  - 2D-gel electrophoresis was used to investigate protein synthesis in leukaemic
      cells from a series of 15 chronic lymphocytic leukaemia (CLL) patients, and in
      non-malignant B-cell populations from different sources. The protein synthesis
      profiles of CD5+ B-cells from umbilical cord blood and from tonsil were
      determined, and the levels of expression of their proteins were observed to be
      similar to the CLL cells. The CD5- cells from cord blood resembled peripheral
      blood B-lymphocytes, and the protein synthesis profile of CD5- cells from tonsils
      was very complex. One protein was also identified which consistently appeared to
      be synthesised at a low level in CD5+ B-cells from tonsil but which was always
      more prominent in CLL cells and other non-malignant B-lymphocytes. On the basis
      of these data it is possible that the closest non-malignant counterpart to CLL is
      the CD5+ B-lymphocyte from cord blood.

PMID- 7515019
TI  - The management of chronic lymphocytic leukemia at a single centre over a 24-year
      period: prognostic factors for survival.
AB  - Over a 24-year period, 137 patients were referred for management of newly
      diagnosed chronic lymphocytic leukemia. One hundred and nineteen patients have
      been reviewed in terms of response to therapy and prognostic factors for
      survival; 18 patients were excluded either because lymph node biopsy was not
      compatible with the diagnosis of CLL (11 patients), or because the lymphocyte
      count at presentation was < 5 x 10(9)/l (seven patients). Patients were staged
      retrospectively according to both the Rai and Binet Classifications. Forty-eight
      per cent (57/119) were deemed not to be in need of any treatment at presentation,
      36 per cent (43/119) have never received any specific therapy. The majority of
      patients received chlorambucil alone, at a dose of 10 mg daily given for 6 weeks,
      followed by a 2-week interval, followed by three, 2-week cycles. The overall
      response rate (complete+partial remission) was 38 per cent. In terms of survival,
      there was a trend in favour of patients who responded to treatment in comparison
      with those who did not but this did not reach statistical significance (P =
      0.07). Correlations with stage were highly significant, the median survivals for
      patients with stage A, B and C disease (Binet) were 12.5, 8 and 3.5 years
      respectively. On univariate analysis, the absolute lymphocyte count at
      presentation was the most significant prognostic factor for survival, patients
      presenting with an absolute lymphocyte count above 50 x 10(9)/l having a less
      favourable prognosis (P = 0.002). However, on multivariate analysis, older age, a
      low hemoglobin, low platelet count, and the presence of lymphadenopathy and fever
      at presentation correlated adversely with survival. Overall, 40 patients died as
      a consequence of CLL or from disease-related causes, 34/40 dying of infection.
      Twenty-one patients developed second cancers. With a median follow-up of 13
      years, these results confirm that the two staging systems can separate patients
      into prognostic groups, however in practice, there is heterogeneity of outcome
      within stage. New approaches are urgently needed.

PMID- 7515018
TI  - Humor: a nursing intervention for the elderly.
AB  - Researchers should investigate humor's value and impact on quality of life of
      elders. Humorous interventions should be studied and compared in elders. The
      effects of endorphin release during laughter is another aspect of humor to be
      studied. Certainly humor is not the answer to all the discomforts encountered by
      older adults, but the positive effects on some cannot be disputed. Humor as a
      noninvasive modality and an adjunct to patient care can be of benefit not only to
      the patient and family, but also to the professional nurse who encounters the
      discomforts of the patient on a daily basis. Humor can aid in viewing the
      pleasures and pains of the world with new perspectives.

PMID- 7515012
TI  - Calcium mobilisation controls tyrosine protein phosphorylation independently of
      the activation of protein kinase C in human platelets.
AB  - We have investigated the regulation of tyrosine proteins phosphorylation by
      intracellular Ca2+ level ([Ca2+]i) and protein kinase C (PKC) during platelet
      stimulation. We found that chelation of extracellular calcium completely
      prevented phosphorylation of tyrosine proteins induced by thapsigargin and
      phorbol 12-myristate 13-acetate (PMA), whereas, when induced by thrombin, it
      prevented a subset of tyrosine proteins. The selective inhibition of PKC by GF
      109203X did not abolish tyrosine protein phosphorylation when induced by thrombin
      and thapsigargin. The results suggest that in human platelets tyrosine protein
      phosphorylation is dependent on [Ca2+]i, although direct PKC activation can also
      induce phosphorylation of tyrosine proteins.

PMID- 7515013
TI  - Characterization of nitric oxide synthase in the opossum esophagus.
AB  - BACKGROUND/AIMS: Nitric oxide mediates the nonadrenergic, noncholinergic neural
      control of esophageal motor function. The purpose of this study was to
      characterize the NO synthase found in the muscularis propria of the opossum
      esophagus and determine its distribution along the esophagus. METHODS: Esophageal
      muscle was homogenized in HEPES buffer and ultracentrifuged. The supernatant was
      exposed to [3H]L-arginine. The [3H]L-citrulline produced by NO synthase was
      separated from [3H]L-arginine with a Dowex AG 50 W-X8 column (Biorad, Hercules,
      CA). Assays were performed in the presence and absence of Ca2+ or reduced
      nicotinamide adenine dinucleotide phosphate (NADPH). The distribution of NO
      synthase activity along the esophagus was determined. RESULTS: The apparent
      Michaelis constant and maximum velocity of NO synthase were 7.5 +/- 1.4 mumol/L L
      arginine and 76.0 +/- 17.3 pmol.mg protein-1.min-1, respectively. The enzyme
      required both Ca2+ and NADPH for activity. Smooth muscle tissue from the lower
      esophageal sphincter and the esophageal body 1-2 cm or 5-6 cm above the lower
      esophageal sphincter differed little in enzymatic activity, ranging from 0.97 to
      1.27 pmol.mg wet wt-1.min-1. Striated muscle had less activity with 0.40 pmol.mg
      wet wt-1.min-1. CONCLUSIONS: These data indicate the presence of a constitutive
      NO synthase in the esophagus of the opossum.

PMID- 7515020
TI  - Sodium channel in isolated human brain macrophages (microglia).
AB  - Human brain macrophages (microglia) have been isolated from mixed brain cell
      cultures initiated from explants of neurosurgical adult human tissue in one step
      according to a method developed for rat microglia. Cells were characterized
      enzyme-histochemically (NDPase) in mixed and immunocytochemically (anti-CD 14) in
      mixed and isolated cultures. Purified cells were used to investigate in more
      detail membrane currents by the patch clamp technique. In 14 cells microdialyzed
      with a standard, K(+)-containing intracellular solution there was no indication
      for a hyperpolarization-induced K(+)-inward current characteristic for newborn
      rat microglia. However, in 12 cells depolarizing pulses initiated a rapidly
      inactivating inward current which was followed by an outward current (in 4
      cells). The outward current appeared to be carried by K+, since it was absent in
      another 18 cells, recorded by micropipettes containing Cs+ instead of K+ as the
      main intracellular cation. The depolarization-induced inward current persisted
      under these conditions. This current was inhibited by tetrodotoxin (5 microM) and
      by substitution of Na+ by choline in the bath solution. It is suggested that this
      Na(+)-current is specifically expressed in macrophages derived from adult brain.

PMID- 7515021
TI  - Oligodendrocytes produce low molecular weight glycoproteins containing N-acetyl-D
      glucosamine in their Golgi apparatus.
AB  - Lectin histochemistry using the Griffonia simplicifolia II lectin (GSL II) has
      revealed a novel group of glycoproteins containing terminal N-acetyl-D
      glucosamine (GlcNAc) residues in oligodendrocytes. The GlcNAc-containing
      glycoproteins were not present in other types of glial cells, but were expressed
      by some neuronal cell populations. Within oligodendrocytes their localization was
      confined to the Golgi apparatus, as determined ultrastructurally. Biochemical
      analyses using tricine/SDS-polyacrylamide gel electrophoresis and western
      blotting with GSL II showed the GlcNAc-containing glycoproteins to be insoluble,
      with molecular masses ranging from 15 to 30 kDa. Our study provides a first
      account of insoluble, GlcNAc-rich 15-30 kDa glycoproteins in oligodendroglia. The
      findings are discussed in the context of the functional significance of other
      known oligodendrocyte glycoproteins.

PMID- 7515022
TI  - Genetic alterations of the putative envelope proteins encoding region of the
      hepatitis C virus in the progression to relapsed phase from acute hepatitis:
      humoral immune response to hypervariable region 1.
AB  - Hypervariable region I (HVRI) of the putative second envelope glycoprotein (gp70)
      of hepatitis C virus (HCV) undergoes sequential alterations at intervals of
      several months during the chronic phase of hepatitis. To evaluate the
      implications of sequence variability in HVRI of HCV, we investigated the sequence
      variability of the whole envelope-protein(gp35 and gp70)-coding regions of HCV
      genome derived from patient M in acute and relapsed phases (8-month interval) of
      hepatitis. From this analysis, we found that a Leu (position 405) in HVRI
      substituted to Pro, and that 4 additional substitutions could be detected in gp70
      during the relapsed phase. Sequence-specific antibody against HVRI derived from
      patient M was first detected in the serum at 8 months after the onset of
      hepatitis, but no other specific antibodies against peptides containing amino
      acid position(s) substituted in regions other than HVRI could be detected.
      Epitope mapping using the sequence of HVRI derived from the acute phase of
      hepatitis was also performed, and a B-cell epitope (positions 397 to 407) of 11
      amino acids was identified. However, the Pro variant at position 405 did not
      display an escape pattern from the antibody produced at 8 months after the onset.
      In addition, we demonstrated the existence of important amino-acid residue
      positions which are recognized by the anti-HVRI antibody produced in patient M
      using introduction point mutations within HVRI.

PMID- 7515025
TI  - Expression of alternatively spliced forms of the CD44 extracellular-matrix
      receptor on human lung carcinomas.
AB  - Expression of isoforms of the CD44 hyaluronan receptor/lymph-node endothelial
      receptor by human tumour cells is thought to play a role in tumour growth and
      metastasis. These isoforms which vary in the length of the extracellular domain
      are generated by differential RNA splicing that involves the 10 alternative exons
      (v1 to v10) encoding the membrane proximal region of the molecule. Several
      tumours have been shown to over-express CD44 containing the v6 exon, and this,
      together with other evidence, has led to the suggestion that v6 may play a
      causative role in tumour metastasis. In this report we have compared the
      expression of CD44 isoforms between different lung tumour lines, including SCLC,
      squamous-cell carcinoma, adenocarcinoma and mesothelioma, using both RT-PCR and
      fluorescent antibody staining with a panel of CD44 exon-specific monoclonal
      antibodies (MAbs). Our results show large differences in vCD44 expression between
      individual tumour lines. Little or no vCD44 containing the metastasis-associated
      v6 exon was detected in most tumours, including the highly metastatic SCLC lines.
      Indeed, the SCLC lines and some squamous-cell carcinomas contained only very low
      levels of either vCD44 or CD44H, indicating that CD44 expression may not always
      correlate with tumour development or dissemination. One of the squamous-cell
      carcinomas studied (HOTZ) was found to express a complex mixture of CD44 splice
      variants similar to the immortalized normal bronchial epithelial line BEAS-2B.
      Cloning and sequencing of vCD44 from the HOTZ cell line yielded several splice
      variants that have also been identified on leukaemic cells, normal keratinocytes
      and activated peripheral-blood lymphocytes.

PMID- 7515024
TI  - Ectopic expression of c-kit in small-cell lung cancer.
AB  - Accumulating evidence suggests that c-kit plays an important role in the
      regulation of growth of at least 3 lineages of stem cells, while only very
      limited data are available on the development of human solid tumors. Our recent
      studies have shown that c-kit transcripts are expressed in a very restricted sub
      set of human solid tumors such as small-cell lung cancer (SCLC). We have also
      conducted an immunohistological study on in situ localization of the c-kit
      protein in various human solid tumors as well as in corresponding fetal and adult
      normal tissues. No c-kit expression was detected in normal bronchial epithelial
      cells or pneumocytes in lung parenchyma of human fetal and adult specimens,
      indicating that the c-kit protein is aberrantly expressed in lung-cancer cells.
      We also found that significant chemotactic response as well as moderate in vitro
      cell growth occurred in SCLC cell lines upon addition of recombinant human stem
      cell factor.

PMID- 7515027
TI  - Topography of NCAM antigenic epitopes recognized by SCLC-cluster-1 antibodies. A
      consensus view.

PMID- 7515028
TI  - Hot spots of antigenicity in the neural cell adhesion molecule NCAM.
AB  - Monoclonal antibodies (MAbs) ranked together as small-cell-lung-cancer (SCLC)
      Cluster I MAbs are directed against the neural cell adhesion molecule NCAM (CD
      56) and have been shown to be useful reagents in SCLC diagnosis and therapy. We
      analyzed the epitopes recognized by 5 SCLC cluster-I MAbs (123C3, 123A8, ERIC-I,
      MB2, and Leu 19) and a closely related anti CD 56 MAb (T199). Our results show
      that within the NCAM molecule Ig-like domain 3 and the segment of about 200 amino
      acids comprised by exons 11-13 are immunodominant regions. The MAbs investigated
      in this study can be combined into 2 groups. Group 1 consists of MAbs MB2, Leu 19
      and T199, which are directed against epitopes located in the 3rd Ig-like domain.
      These MAbs recognize closely related but distinctive conformational epitopes.
      MAbs ERIC-1, 123C3 and 123A8 form Group 2 and are directed against a membrane
      proximal region of the NCAM molecule. The data presented suggest that the 3 Group
      2 MAbs bind to closely related or identical epitopes.

PMID- 7515023
TI  - T-helper- and accessory-cell-independent cytotoxic responses to human tumor cells
      transfected with a B7 retroviral vector.
AB  - As a means to increase the immunogenicity of tumor cells, we have developed a
      retroviral vector to transfect human B7, a molecule capable of delivering co
      stimulatory signals to T cells. Three different tumors, a melanoma, an ovarian
      carcinoma and a myelomonocytic leukemia, were transfected with high efficiency.
      When compared for their capacity to stimulate allogeneic T cells, B7+ but not B7-
      tumor cells were able to stimulate strong proliferative and cytotoxic responses.
      The effector CTL generated recognised B7+ and B7- cells as well as untransfected
      tumor cells, indicating that B7 is required in the inductive but not the effector
      phase of the response. Remarkably, B7+ tumor cells were able to induce cytotoxic
      responses both by CD4-depleted and by CD8-purified T cells, demonstrating that
      expression of B7 is at the same time necessary and sufficient to induce a
      cytotoxic response in the absence of T-helper cells and accessory cells.

PMID- 7515030
TI  - Use of the immunotoxin N901-blocked ricin in patients with small-cell lung
      cancer.
AB  - In patients with small-cell lung cancer (SCLC), relapse with resistant disease
      often causes death. N901-blocked ricin (N901-bR), a murine monoclonal antibody
      (MAb)-blocked ricin immunotoxin, is a potential therapeutic for SCLC. N901-bR
      targets CD56, present on SCLC and cells of neuro-ectodermal origin. N901-bR kills
      up to 5 logs of CD56-positive cells at a concentration of 0.25 nM, while CD56
      negative cells require 1000-fold more drug to achieve similar cell kill. We
      treated 21 patients with relapsed or refractory SCLC with a single 7-day course
      of N901-bR as a continuous infusion. We determined the MTD and toxicity profile,
      demonstrated drug binding to tumor cells in biopsies of lung, liver and bone
      marrow, and determined the time to development of human anti-mouse and anti-ricin
      antibodies. One patient had a documented PR and 6 patients demonstrated stable
      disease. Toxicity included transient elevation of liver enzymes, mild
      thrombocytopenia, hypoalbuminemia, fever, malaise, and evidence of capillary leak
      syndrome. Toxicities were controllable and reversible. No apparent drug-related
      central- or peripheral-nervous-system toxicity was noted by serial neurologic
      examinations, EMGs, and nerve conduction studies. Trials of N901-bR are planned
      in SCLC patients achieving CR and PR following chemoradiotherapy, and in
      relapsed/refractory patients. Anti-B4-bR will be added as an immunosuppressant in
      order to permit delivery of multiple courses of N901-bR. Additional trials will
      investigate synergy with conventional chemotherapeutics and the use of N901-bR as
      a sensitizing agent for chemotherapy-resistant tumors.

PMID- 7515029
TI  - Detection of the neural cell adhesion molecule (NCAM) in serum of patients with
      small-cell lung cancer (SCLC) with "limited" or "extensive" disease, and bone
      marrow infiltration.
AB  - The neural cell adhesion molecule (NCAM) is a tumour-related antigen found on the
      surface of small-cell lung cancer (SCLC). NCAM exists in several molecular forms,
      including a soluble isoform. We have measured serum levels of NCAM using an
      enzyme immunoassay with 2 antibodies, NCC-LU-246 and NCC-LU-243, that react with
      different epitopes on the NCAM molecule. NCAM activity from 83 patients with
      active SCLC, either pre-treatment, progressing or in relapse was significantly
      higher than in 70 patients on follow-up. Overall, 40% of patients with active
      SCLC and 7% patients on follow-up had serum levels of NCAM > 2SD above controls;
      61% of patients with relapsed SCLC had elevated levels of NCAM. Pre-treatment
      NCAM levels were significantly higher in 35 patients with "extensive" disease
      than in 19 patients with "limited" disease. Serum NCAM activity was also
      significantly higher in patients with tumour infiltration of the bone marrow.
      This difference could not be explained solely by the presence of "extensive"
      disease. Serum NSE levels in these patients were correlated with NCAM activity.
      The presence of raised serum NCAM in active disease and in patients in relapse
      suggests that this antigen could be used as a target for antibody-directed
      therapy of micrometastases.

PMID- 7515031
TI  - SCLC-cluster-2 antibodies detect the pancarcinoma/epithelial glycoprotein EGP-2.
AB  - Analysis of the antibodies submitted to the 3 International Workshops on Small
      Cell Lung Cancer Antigens has resulted in the identification of 15 clusters of
      antibody reactivity. One of these clusters, named SCLC cluster 2, is
      characterized by reactivity against an epithelium-associated 38 kDa membrane
      glycoprotein. SCLC cluster 2, and a number of other antibodies with reportedly
      similar reactivities, were shown to recognize a protein encoded by the GA733-2
      gene, whereas the newly defined SCLC cluster 13 antibodies react with the GA733-1
      gene product. We propose to call the antigen detected by SCLC-cluster-2
      antibodies "epithelial glycoprotein 2" (EGP-2), and the epithelium-associated
      glycoprotein recognized by antibodies clustered in SCLC cluster 13 (see elsewhere
      in this volume) "epithelial glycoprotein 1" (EGP-1). A short overview of the
      characteristics of both proteins and the applications of anti-EGP-2 antibodies is
      presented.

PMID- 7515032
TI  - Epitope mapping of SCLC-cluster-2 MAbs and generation of antibodies directed
      against new EGP-2 epitopes.
AB  - Western blot analysis proved that all cluster-2 MAbs recognize identical or
      overlapping disulfide-bond-dependent epitopes, indicating the presence of a
      disulfide-bond-stabilized EGP-2 domain carrying highly immunodominant non-linear
      epitopes. The apparent immunodominance of this domain makes it difficult to
      generate and select antibodies against other potentially useful EGP-2 epitopes.
      Using PCR, we have generated mutant EGP-2 cDNA (delta EGP-2) from which the
      coding sequences for a putative immunodominant 6-kDa intra-chain loop structure
      has been removed. delta EGP-2 transfected COS-7 cells reacted with MM104, an
      antibody detecting a linear epitope on EGP-2, but were not recognized by any
      cluster-2 MAb. To generate new anti-EGP-2 antibodies we constructed another
      mutant EGP-2 protein (delta EGP-2) from which additional domains, irrelevant for
      antibody generation (signal peptide, trans-membrane and cytoplasmic domains),
      were removed. delta EGP-2 was introduced in a prokaryotic expression system that
      adds a polyhistidine affinity tag to the delta EGP-2 N-terminus, making possible
      one-step purification by immobilized metal-ion-affinity chromatography (IMAC).
      Western blot analysis showed that sera derived from mice immunized with purified
      delta EGP-2 had high-titer antibodies to reduced EGP-2 samples. We conclude that
      the availability of prokaryotic and eukaryotic EGP-2-expression constructs might
      facilitate the selection of new anti-EGP-2 MAbs otherwise difficult to obtain.

PMID- 7515033
TI  - Immunological evidence for co-expression of cluster-5 and cluster-5A small cell
      lung cancer antigen on a single molecule.
AB  - We have investigated immunologically the molecular association of the cell
      surface sialoglycoprotein antigens cluster-5 (CL-5) and cluster-5A (CL-5A), known
      to be co-expressed in human small-cell lung cancer (SCLC). CL-5 antigen is
      exclusively defined by IgM antibodies as represented by MAb LAM8, whereas CL-5A
      antigen is exclusively defined by IgG antibodies as represented by MAbs SWA20 and
      SEN31. Because of the unavailability of purified antigens, the question of the
      molecular relationship between these antigens was addressed by immunological
      studies. We generated an anti-anti-idiotypic MAb of the IgG isotype using a CL-5
      antigen-mimicking anti-idiotype defined by rat MAb Ly8-229 as an immunogen to
      circumvent the avidity problems observed with the IgM MAb LAM8 in binding
      competition experiments. In addition, we developed a heterologous double antibody
      sandwich assay able to identify circulating CL-5/5A antigens in pre-treatment
      sera of patients with SCLC. The results of both types of immunological studies
      demonstrated the expression of CL-5 and CL-5A antigens on a single molecule, both
      in cellular assays and in assays detecting antigens shed into the serum of
      patients with SCLC.

PMID- 7515026
TI  - Reactivity of lung tumors with lung-derived and non-lung-derived monoclonal
      antibodies.
AB  - The reactivity of 74 lung-derived monoclonal antibodies (MAbs) provided by the
      Third International Workshop on Lung Tumor Antigens and of 41 non-lung-derived
      commercially available MAbs against sections of 15 lung tumors of various
      histologic types was investigated by immunohistochemistry. Three MAbs with
      specificity for human neural-cell adhesion molecule (H-NCAM) and 3 MAbs with
      specificity for small-cell lung carcinoma (SCLC) were able to distinguish between
      neuro-endocrine (NE) and non-NE tumors. Fifteen MAbs stained non-small-cell
      carcinomas (NSCLC) but not SCLC. Neuron-specific enolase (NSE) stained all NE
      tumors but also some of the non-NE tumors. Two MAbs showed specificity for
      mesotheliomas. Carcino-embryonic MAb strongly stained all SCLC and NSCLC. Among
      MAbs with lymphoid-cell specificities, Leu 7 (CD57) stained SCLC, but not NSCLC.
      LN2 (CD45R), LN3 (HLA-DR), Leu 22 (CD43) and BLA 36 reacted with NSCLC and were
      non-reactive with SCLC. Some of the lung-derived MAbs showed immune staining of
      lymphoma and melanoma.

PMID- 7515034
TI  - Cluster-10 lung-cancer antibodies recognize NSPs, novel neuro-endocrine proteins
      associated with membranes of the endoplasmic reticulum.
AB  - We have identified a novel gene (the NSP gene) encoding 3 transcripts and coding
      for 3 neuroendocrine-specific proteins (NSPs), by screening a cDNA expression
      library of the small-cell lung-cancer (SCLC) cell line NCI-H82 with the cluster
      10 lung-cancer antibodies RNL2 and RNL3. The 3 transcripts code for NSPs with
      apparent molecular weights of 135 kDa (NSP-A), 43 to 45 and 35 kDa (NSP-B) and 23
      kDa (NSP-C). NSP-A and NSP-B are recognized by antibodies RNL2 and RNL3, while
      second-generation antibodies, specifically recognizing NSP-A and NSP-C, have been
      produced after immunization with a hybrid protein obtained after bacterial
      expression of the largest NSP-transcript or with a synthetic peptide specific for
      NSP-C. The NSPs exhibit a highly restricted distribution pattern and are found
      mainly in neural and neuro-endocrine cell types, and in neuro-endocrine tumours.
      Of the different types of lung tumours, mainly SCLC and carcinoids were positive
      in immunocytochemical assays using the anti-NSP antibodies, while non-SCLC were
      in general negative. The subcellular distribution of the NSPs was studied in
      human SCLC cell lines. They do not co-localize with components typical of neuro
      endocrine granules, such as synaptophysin and chromogranin. The use of NSP
      antibodies in the immunofluorescence technique applied to cultured SCLC cells,
      made it obvious that these proteins localize in the endoplasmic reticulum. Cell
      fractionation procedures, monitored by immunoblotting assays, indicated an
      association of the NSPs with the microsomal fraction, from which they could be
      solubilized with Triton X-100. Gel filtration studies with this solubilized
      fraction revealed that NSPs form supramolecular aggregates with a molecular
      weight of more then 500 kDa.

PMID- 7515035
TI  - Antibodies to the 4-mer repeat of the ring-infected erythrocyte surface antigen
      (Pf155/RESA) protect against Plasmodium falciparum malaria.
AB  - To investigate the protective role of antibodies to the ring-infected erythrocyte
      surface antigen (Pf155/RESA) epitopes against Plasmodium falciparum clinical
      malaria, a cohort study was conducted in a Malagasy village over 7 months. In the
      304 individuals included, 127 experienced P. falciparum attacks of under 1500
      parasites/microliters with no clinical symptoms (protected individuals) and 177
      experienced at least one clinical or preclinical P. falciparum attack requiring
      therapy (unprotected individuals). Antibodies to whole Pf155/RESA, to single
      epitopes of the 3' terminus, (EENV)4 and EENVEHDA(EENV)2 had higher responses in
      protected than in unprotected individuals (P = 0.006, P = 0.005, P = 0.05
      respectively). Within the whole pattern of antibodies to the Pf155/RESA epitopes,
      only anti-R4 was related to protection independently of age and anti-wR. The
      Pf155/RESA 4-mer repeated epitope might be of interest for inclusion in a vaccine
      against the asexual blood stages of P. falciparum.

PMID- 7515036
TI  - Health visitors' role in services for children with disabilities.
AB  - Health visitors play a vital role within the specialist child development team
      providing support for children with disabilities and their families, write
      Margaret Yerbury and Jim Thomas. They report the findings of a study which
      revealed the significant contribution of health visitors and nurses in such teams
      in contributing to the ability of families to develop skills to meet their
      child's special needs and maximise the child's potential. The study also revealed
      concern among parents and professionals where no specialist health visiting
      support was available. This vital service may be at risk from cuts in health
      visiting services, they warn.

PMID- 7515037
TI  - WIN 64821, a novel neurokinin antagonist produced by an Aspergillus sp. I.
      Fermentation and isolation.
AB  - WIN 64821, a nonpeptide neurokinin antagonist, was isolated from a strain of
      Aspergillus sp., SC319. The compound was produced in different fermentation media
      with greatest yields observed when the culture was grown in a synthetic medium
      supplemented with L-tryptophan and L-phenylalanine. After 6 days fermentation,
      yields greater than 600 mg/liter were obtained. Two analogs of WIN 64821 were
      also identified in the culture extracts and subsequently tested for biological
      activity. WIN 64821 was the most potent compound isolated from this culture and
      exhibited activity as a substance P-binding inhibitor with submicromolar potency
      against the human neurokinin 1 receptor.

PMID- 7515039
TI  - WIN 64821, a novel neurokinin antagonist produced by an Aspergillus sp. III.
      Biosynthetic analogs.
AB  - WIN 64821 (1) is a substance P (SP) antagonist isolated from a fungal culture
      (Aspergillus sp., SC319). It is a symmetrical dimer biosynthesized from four
      aromatic amino acid molecules: each equivalent half of the dimer is constructed
      from one molecule of phenylalanine (Phe) and one molecule of tryptophan (Trp).
      Feeding analogs of Phe, Trp, and other amino acids to intact cells of SC319 has
      yielded 36 biosynthetic analogs of WIN 64821. The analogs fall into three
      categories: substitutions on the indoline ring, substitutions on the Phe-derived
      phenyl ring, and replacement of the phenyl ring by an aliphatic group. In
      addition, these directed biosynthesis experiments generated asymmetrical dimers
      (derived from three amino acids) and, often, symmetrical dimers (derived from two
      amino acids). The relative SP binding affinities of several analogs suggest
      involvement of both the indoline and phenyl moieties in SP receptor binding.

PMID- 7515040
TI  - The response of a Bacillus subtilis temperature-sensitive sigA mutant to heat
      stress.
AB  - The mutant sigA allele of Bacillus subtilis DB1005 was confirmed to be
      temperature sensitive (ts) and transferable among strains of B. subtilis by
      chromosomal transformation and gene conversion. This ts sigA allele had a
      pleiotropic effect on gene expression of DB1005. The induction of certain heat
      shock proteins in DB1005 was markedly less significant than that observed in the
      wild-type strain (DB2) under heat stress. In contrast, some proteins required for
      coping with oxidative stress and glucose starvation were induced abruptly in
      DB1005 but not in DB2. Heat induction of the groEL gene in vivo at both
      transcription and translation levels was much lower in DB1005 than in DB2.
      Besides, the putative sigma A-type promoter from the groESL operon of B. subtilis
      was able to be transcribed by the reconstituted sigma A RNA polymerase in vitro
      at both 37 and 49 degrees C. These results strongly suggest that the expression
      of the groEL gene of B. subtilis under heat stress is regulated at least in part
      by sigma A at the level of transcription. Our results also showed that DB1005 did
      not respond too differently from the wild type to ethanol stress, except after a
      relatively long exposure.

PMID- 7515041
TI  - Cloning and sequencing of a 2,5-dichloro-2,5-cyclohexadiene-1,4-diol
      dehydrogenase gene involved in the degradation of gamma-hexachlorocyclohexane in
      Pseudomonas paucimobilis.
AB  - In Pseudomonas paucimobilis UT26, gamma-hexachlorocyclohexane (gamma-HCH) is
      converted to 2,5-dichloro-2,5-cyclohexadiene-1,4-diol (2,5-DDOL), which is then
      metabolized to 2,5-dichlorohydroquinone. Here, we isolated from the genomic
      library of UT26 two genes which expressed 2,5-DDOL dehydrogenase activity when
      they were transformed into P. putida and Escherichia coli. Both gene products had
      an apparent molecular size of 28 kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The first gene, named linC, located separately from the two
      genes (linA and linB) which we had already cloned as genes involved in the gamma
      HCH degradation. The other, named linX, located about 1 kb upstream of the linA
      gene encoding gamma-HCH dehydrochlorinase. A gamma-HCH degradation-negative
      mutant, named UT72, which lacked the whole linC gene but had the intact linX gene
      was isolated. The linC gene given in a plasmid could complement UT72. These
      results strongly suggest that the linC gene but not the linX gene is essential
      for the assimilation of gamma-HCH in UT26. Deduced amino acid sequences of LinC
      and LinX show homology to those of members of the short-chain alcohol
      dehydrogenase family.

PMID- 7515038
TI  - WIN 64821, a novel neurokinin antagonist produced by an Aspergillus sp. II.
      Biological activity.
AB  - WIN 64821, a secondary metabolite produced by Aspergillus sp. (ATCC 74177) was
      found to inhibit radiolabeled substance P (SP) binding in a variety of tissues,
      including those of human origin. This compound inhibited, in a competitive
      manner, the binding of SP with Ki values ranging from 0.24 microM in human
      astrocytoma U-373 MG cells to 7.89 microM in rat submaxillary membranes.
      Additionally, WIN 64821 was found to inhibit 125I-NKA binding to the NK2 receptor
      in human tissue at a concentration equivalent to its NK1 activity (0.26 microM).
      The inhibitory activity of WIN 64821 against an NK3 selective ligand, 3H
      senktide, was found to be much weaker (Ki = 15.2 microM). WIN 64821 was also
      evaluated in NK1 functional assays and was found to be a competitive antagonist
      of SP-induced contractility in the guinea pig ileum (pA2 = 6.6) as well as an
      inhibitor of SP-induced 45Ca2+ efflux from human astrocytoma U-373 MG cells (IC50
      = 0.6 microM). In a rat vas deferens model, WIN 64821 inhibited eledoisin-induced
      contractility with an IC50 of 3.4 microM indicating functional antagonism at the
      NK2 receptor. The data presented in this study provide biochemical,
      pharmacological and functional evidence supporting WIN 64821 as a competitive
      neurokinin antagonist.

PMID- 7515044
TI  - Prolonged circulation of activated platelets following plasmapheresis.
AB  - The extent and duration of in vivo platelet activation were determined in 12
      volunteer donors undergoing automated plasmapheresis. Expression of P-selectin,
      activated GpIIb/IIIa, and platelet microparticle formation were measured by flow
      cytometry on peripheral blood samples obtained immediately before and after
      plasmapheresis and at 24 hour intervals thereafter for up to 3 days. Although no
      adverse effects were noted in any donor, immediately after apheresis 3-87% of
      circulating platelets expressed P-selectin; by 48 hours, 0.5-50% expressed P
      selectin; and by 72 hours, all donors studied had fewer than 5% P-selectin
      expression on circulating platelets. Results were similar for the expression of
      the activated conformation of GpIIb/IIIa. There was a positive correlation with
      in vitro P-selectin expression in response to ADP in the pre-apheresis sample and
      the number of platelet microparticles detected in the donor following
      plasmapheresis. In addition, the percent expression of P-selectin and activated
      GpIIb/IIIa in response to ADP was reproducible in each individual studied on five
      separate occasions (CV < or = 8%). Platelets activated during plasmapheresis
      using an automated device may circulate for at least 48 hours, and pre
      plasmapheresis response of platelets to the agonist ADP correlated with platelet
      microparticle formation post-plasmapheresis.

PMID- 7515045
TI  - Collection efficiency on the Fenwal CS3000 when using filgrastim (recombinant
      methionyl human granulocyte colony-stimulating factor) as a peripheral blood stem
      cell mobilization agent.
AB  - The collection efficiency (CE) of the Fenwal CS3000 in collecting peripheral
      blood stem cells during post-chemotherapy recovery phase ranges from 58% to 73%.
      Recently filgrastim (recombinant methionyl human granulocyte colony-stimulating
      factor [G-CSF]) has also been shown to be effective as a mobilization agent
      although mobilization occurs during elevated and not low normal leukocyte counts.
      We compared the mononuclear cell (MNC) CE and the myeloid progenitor cell (CFU
      GM) CE among 11 patients with G-CSF mobilization (33 procedures) and 19 patients
      during recovery following myelosuppression chemotherapy (93 procedures). Pre
      apheresis leukocyte, neutrophil, MNC, and PB CFU-GM counts were significantly
      higher in the G-CSF group, while the granulocyte percentage in the apheresis
      products was similar in both groups. Both MNC CE (81.8 +/- 4.5% vs. 64 +/- 2.4%)
      and CFU-GM CE (79.5 +/- 10.5% vs. 55.8 +/- 3.5%) were higher in the G-CSF group.
      Only the pre-apheresis MNC count showed an independently significant correlation
      for both CE (P < .001). The higher CE in the G-CSF group can only be partly
      explained by a rise in MNC count during apheresis. These data suggest that the
      blood cell separator works better with leukocytosis, and especially with a higher
      MNC count. The improvement in CE is another benefit of G-CSF mobilization over
      chemotherapy mobilization.

PMID- 7515042
TI  - Cloning and analysis of duplicated rfbM and rfbK genes involved in the formation
      of GDP-mannose in Escherichia coli O9:K30 and participation of rfb genes in the
      synthesis of the group I K30 capsular polysaccharide.
AB  - The rfbO9 gene cluster, which is responsible for the synthesis of the
      lipopolysaccharide O9 antigen, was cloned from Escherichia coli O9:K30. The gnd
      gene, encoding 6-phosphogluconate dehydrogenase, was identified adjacent to the
      rfbO9 cluster, and by DNA sequence analysis the gene order gnd-rfbM-rfbK was
      established. This order differs from that described for other members of the
      family Enterobacteriaceae. Nucleotide sequence analysis was used to identify the
      rfbK and rfbM genes, encoding phosphomannomutase and GDP-mannose
      pyrophosphorylase, respectively. In members of the family Enterobacteriaceae,
      these enzymes act sequentially to form GDP-mannose, which serves as the activated
      sugar nucleotide precursor for mannose residues in cell surface polysaccharides.
      In the E. coli O9:K30 strain, a duplicated rfbM2-rfbK2 region was detected
      approximately 3 kbp downstream of rfbM1-rfbK1 and adjacent to the remaining genes
      of the rfbO9 cluster. The rfbM isogenes differed in upstream flanking DNA but
      were otherwise highly conserved. In contrast, the rfbK isogenes differed in
      downstream flanking DNA and in 3'-terminal regions, resulting in slight
      differences in the sizes of the predicted RfbK proteins. RfbMO9 and RfbKO9 are
      most closely related to CpsB and CpsG, respectively. These are isozymes of GDP
      mannose pyrophosphorylase and phosphomannomutase, respectively, which are thought
      to be involved in the biosynthesis of the slime polysaccharide colanic acid in E.
      coli K-12 and Salmonella enterica serovar Typhimurium. An E. coli O-:K30 mutant,
      strain CWG44, lacks rfbM2-rfbK2 and has adjacent essential rfbO9 sequences
      deleted. The remaining chromosomal genes are therefore sufficient for GDP-mannose
      formation and K30 capsular polysaccharide synthesis. A mutant of E. coli CWG44,
      strain CWG152, was found to lack GDP-mannose pyrophosphorylase and lost the
      ability to synthesize K30 capsular polysaccharide. Wild-type capsular
      polysaccharide could be restored in CWG152, by transformation with plasmids
      containing either rfbM1 or rfbM2. Introduction of a complete rfbO9 gene cluster
      into CWG152 restored synthesis of both O9 and K30 polysaccharides. Consequently,
      rfbM is sufficient for the biosynthesis of GDP-mannose for both O antigen and
      capsular polysaccharide E. coli O9:K30. Analysis of a collection of serotype O8
      and O9 isolates by Southern hybridization and PCR amplification experiments
      demonstrated extensive polymorphism in the rfbM-rfbK region.

PMID- 7515046
TI  - Effects of feto-placental markers with plasma exchange in pregnancy.
AB  - To evaluate changes in feto-placental markers with plasma exchange in pregnancy,
      two patients at varying stages of pregnancy referred to a tertiary care hospital
      and requiring plasma exchange for intercurrent problems were evaluated. Alpha
      fetoprotein, human chorionic gonadotropin, and free estriol were sequentially
      measured in the patients' plasma and in the fluid removed, thus permitting
      calculations of permeability rates and clearances. Despite markedly different
      molecular weights, all three feto-placental markers had similar permeabilities
      and clearances. While in both patients maternal levels of alpha-fetoprotein and
      human chorionic gonadotropin decreased rapidly with plasma separation and
      rebounded rapidly to baseline, free estriol responded differently and did not
      appear to decrease with therapy. Maternal levels of feto-placental markers only
      transiently changed with plasma exchange during pregnancy and rapidly returned to
      baseline with no apparent consequences to the pregnancy.

PMID- 7515043
TI  - Structural and antigenic characteristics of Campylobacter coli FlaA flagellin.
AB  - The polar flagellar filament of Campylobacter coli VC167 is composed of two
      highly related (98%) flagellin subunit proteins, FlaA and FlaB, whose antigenic
      specificities result from posttranslational modification. FlaA is the predominant
      flagellin species, and mutants expressing only FlaA form a full-length flagellar
      filament. Although the deduced M(r) of type 2 (T2) FlaA is 58,884 and the
      apparent M(r) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis is
      59,500, the solution weight-average M(r) by sedimentation analysis was 63,000.
      Circular dichroism studies in the presence or absence of 0.1% sodium dodecyl
      sulfate or 50% trifluorethanol showed that the secondary structure of T2 FlaA
      flagellin was altered, with alpha-helix structure being increased to 25% in the
      nonpolar environment. The molecule also contained 35 to 48% beta-sheet and 11 to
      29% beta-turn structure. Mimeotope analysis of octapeptides representing the
      sequence of FlaA together with immunoelectron microscopy and enzyme-linked
      immunosorbent assay with a panel of antisera indicated that many residues in
      presumed linear epitopes were inaccessible or nonepitopic in the assembled
      filament, with the majority being in the N-terminal 337 residues of the 572
      residue flagellin. Residues at the carboxy-terminal end of the T2 FlaA subunit
      also become inaccessible upon assembly. Digestion with trypsin, chymotrypsin, and
      endoproteinase Glu-C revealed a protease-resistant domain with an approximate
      M(r) of 18,700 between residues 193 and 375. Digestion with endoproteinase Arg-C
      and endoproteinase Lys-C allowed the mapping of a segment of surface-exposed FlaA
      sequence which contributes serospecificity to the VC167 T2 flagellar filament at
      residues between 421 and 480.

PMID- 7515049
TI  - Cyclosporin A inhibits Ca2+/calmodulin-dependent protein phosphatase and
      secretion in pancreatic acinar cells.
AB  - The immunosuppressant cyclosporin A (CsA) was utilized as a highly specific
      inhibitor of the Ca2+/calmodulin-dependent protein phosphatase, PP2B in rat
      pancreatic acinar cells. Treatment of cells with CsA for 20 min resulted in a
      concentration-dependent inhibition of PP2B that was maximal (> 90%) at 1 microM
      and exhibited an IC50 of 65 nM. CsA also inhibited cholecystokinin-, 100 pM, or
      carbamylcholine-, 10 microM, induced amylase release in a concentration-dependent
      manner. A maximal inhibition to 55% of stimulated control cells occurred at 1
      microM CsA with half-maximal inhibition occurring at approximately 200 nM.
      Secretion in response to 1 microM 12-O-tetradecanoylphorbol-13-acetate (TPA) was
      uneffected by CsA treatment. Conversely, amylase release stimulated by the Ca2+
      mobilizing agent, thapsigargin, when added alone at 2 microM or in combination
      with TPA, was inhibited by CsA to 66 and 61% of control cells, respectively.
      These data indicate that CsA-mediated inhibition occurs only when stimulation
      involves an increase in intracellular Ca2+. In addition, analogues of CsA, 6
      methyl-alanine-CsA, and 11-methyl-leucine-CsA had no effect on PP2B activity or
      amylase secretion. The chemically distinct immunosuppressant, FK506, produced
      only partial inhibition of PP2B activity and did not significantly inhibit
      amylase secretion at concentrations up to 1 microM. Two-dimensional gel
      electrophoresis of proteins from 32P-labeled acinar cells revealed that CsA
      specifically blocked the cholecystokinin-stimulated dephosphorylation of a 24-kDa
      protein in a concentration range similar to that seen for inhibition of
      secretion. Using 32P-labeled cytosol and purified calcineurin, a Ca(2+)- and
      calmodulin-dependent dephosphorylation of the 24-kDa protein was also
      demonstrated in vitro. Collectively, these data indicate that the Ca2+/calmodulin
      dependent protein phosphatase, PP2B, plays a significant role in stimulus
      secretion coupling in pancreatic acinar cells.

PMID- 7515050
TI  - Evidence for a bidomain structure of constitutive cerebellar nitric oxide
      synthase.
AB  - Nitric oxide synthase (NOS) catalyzes the NADPH-dependent, Ca2+/calmodulin
      dependent formation of NO and citrulline from L-arginine and molecular oxygen.
      The localization of the heme-binding consensus sequence in the NH2-terminal half
      of NOS and of the binding sequences for nucleotides (FMN and FAD) in the COOH
      terminal half suggests a bidomain structure. In addition, the presence of a
      putative calmodulin-binding sequence between the heme- and flavin-binding domains
      of the enzyme suggests a role for calmodulin in modulating a spatial orientation
      of these domains that is required for catalytic activity. First, to determine the
      effects of calmodulin and the functionality of the separated domains,
      Ca2+/calmodulin binding-induced conformational changes in NOS were measured by
      fluorescence quenching, from which a binding constant of approximately 1 nM for
      calmodulin was calculated. Second, electron transport to various artificial
      acceptors was measured. The addition of Ca2+/calmodulin increased cytochrome c
      reduction from 10-15-fold while stimulating the rate of 2,6
      dichlorophenolindophenol and ferricyanide reduction only slightly, if at all.
      Calmodulin stimulation of NOS results in NADPH-mediated cytochrome c reduction,
      which is sensitive to superoxide dismutase, and the reduction of acetylated
      cytochrome c, which is only weakly reducible by unstimulated NOS. Thus, this
      stimulated activity is presumably superoxide anion-mediated. Third, limited
      proteolysis of NOS in the absence of calmodulin resulted in a time-dependent
      increase in cytochrome c reductase activity, which was not inhibitable by
      superoxide dismutase, and a decrease in catalysis of NO formation. SDS
      polyacrylamide gel electrophoresis analysis of the tryptic digest demonstrated
      the formation of approximately 89- and approximately 79-kDa fragments. Sequence
      analysis of the peptides confirmed that trypsin cleaves the enzyme in the
      putative calmodulin-binding region beginning with Ala728. This region was
      protected from proteolysis by the addition of Ca2+/calmodulin. The separated NH2
      terminal domain exhibited the characteristic spectrum of bound heme, while the
      COOH-terminal domain showed the characteristic spectrum of bound flavins. Other
      cleavage patterns were obtained in the presence of calmodulin. The data
      demonstrate that the heme- and flavin-binding domains of NOS can be isolated in
      functionally intact forms.

PMID- 7515048
TI  - Inositol polyanions. Noncarbohydrate inhibitors of L- and P-selectin that block
      inflammation.
AB  - Selectins are cell adhesion molecules known to support the initial attachment of
      leukocytes to inflamed vascular endothelium through their recognition of
      carbohydrate ligands such as the tetrasaccharide sialyl Lewisx (Neu5Ac alpha 2
      3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-). In the present study, we describe the
      inhibition of L- and P-selectin function by inositol polyanions, simple 6-carbon
      ring structures that have multiple ester-linked phosphate or sulfate groups. In a
      purified component competition assay, binding of L- and P-selectin-Ig fusion
      proteins to immobilized bovine serum albumin-sialyl Lewisx neoglycoprotein was
      inhibited by inositol hexakisphosphate (InsP6, IC50 = 2.1 +/- 1.4 microM and 160
      +/- 40 microM), by inositol pentakisphosphate (InsP5, IC50 = 1.4 +/- 0.2 and 260
      +/- 40 microM), and by inositol hexakissulfate (InsS6, IC50 = 210 +/- 80 microM
      and 2.8 +/- 0.9 mM); E-selectin-Ig binding was unaffected. Inositol polyanions
      diminished the adhesion of LS180 colon carcinoma cells to plates coated with L-
      and P-selectin-Ig but not with E-selectin-Ig. Inositol polyanions blocked
      polymorphonuclear leukocyte (PMN) adhesion to COS cells expressing recombinant
      transmembrane P-selectin but not to those expressing E-selectin. In addition,
      inositol polyanions diminished PMN adhesion to activated endothelial cells under
      rotation-induced shear stress, a process known to require L-selectin function. In
      vivo, the effects of inositol polyanions were studied in two murine models of
      acute inflammation. Intravenously administered InsP6 (two doses of 40 mumol/kg)
      inhibited PMN accumulation in thioglycolate-induced inflammation (55 +/- 10%
      inhibition) and in zymosan-induced inflammation (61 +/- 4% inhibition). InsP5 and
      InsS6 also inhibited inflammation in these models, although higher doses were
      required for InsS6. In conclusion, inositol polyanions are noncarbohydrate small
      molecules that inhibit L- and P-selectin function in vitro and inflammation in
      vivo.

PMID- 7515051
TI  - Molecular cloning of a murine N-acetylgalactosamine transferase cDNA that
      determines expression of the T lymphocyte-specific CT oligosaccharide
      differentiation antigen.
AB  - Two monoclonal antibodies termed CT1 and CT2 define a cell surface
      oligosaccharide molecule expressed on restricted populations of murine
      lymphocytes. This oligosaccharide structure is largely associated with the
      extracellular domain of the CD45 family of tyrosine phosphatases, molecules
      required for lymphocytes to proliferate in response to antigen stimulation.
      Previous work has shown that the oligosaccharide structure recognized by the CT
      antibodies is identical, at least in part, to that of the human Sda blood group,
      a structure formed through enzymatic addition of N-acetylgalactosamine in beta
      1,4-linkage to a sub-terminal galactose substituted with an alpha 2,3-linked N
      acetylneuraminic acid residue. We have used a mammalian transient expression
      cloning approach to isolate a murine cDNA that determines expression of an
      oligosaccharide structure recognized by the CT antibodies as well as human anti
      Sda serum. The nucleotide sequence predicts a 510-amino acid type II
      transmembrane protein characteristic of other mammalian glycosyltransferases.
      Enzymatic characterization of the protein expressed by this cDNA demonstrates
      that it encodes a beta 1,4-N-acetylgalactosamine transferase activity that can
      add to the low molecular weight acceptor 3'-sialyl-N-acetyllactosamine, to form
      the nonreducing terminal tetrasaccharide Sda blood group structure. This cDNA
      shares 51% nucleotide sequence identity with a cDNA encoding the human GM2/GD2
      synthase, particularly throughout the regions encoding their putative catalytic
      domains. Southern blot analysis demonstrates that these two cDNA's represent
      distinct loci in the murine genome. The CT-GalNAc transferase cDNA isolated here
      represents a tool with which to define the role(s) of lymphocyte cell surface CT
      determinants, and may facilitate the isolation of the human Sda blood group locus
      through cross-hybridization approaches.

PMID- 7515047
TI  - Amino acid residues lining the chloride channel of the cystic fibrosis
      transmembrane conductance regulator.
AB  - The cystic fibrosis transmembrane conductance regulator forms a chloride channel
      that is regulated by phosphorylation and intracellular ATP levels. The structure
      of the channel-forming domains is undetermined. To identify the residues lining
      this channel we substituted cysteine, one at a time, for 9 consecutive residues
      (91-99) in the M1 membrane-spanning segment. The cysteine substitution mutants
      were expressed in Xenopus oocytes. We determined the accessibility of the
      engineered cysteine to charged, sulfhydryl-specific methanethiosulfonate reagents
      added extracellularly. We assume that, among residues in membrane-spanning
      segments, only those lining the channel will be accessible to react with these
      hydrophilic reagents and that such a reaction would irreversibly alter conduction
      through the channel. Only the cysteines substituted for Gly-91, Lys-95, and Gln
      98 were accessible to the reagents. We conclude that these residues are in the
      channel lining. The periodicity of these residues is consistent with an alpha
      helical secondary structure.

PMID- 7515052
TI  - Exogenous receptor-associated protein binds to two distinct sites on human
      fibroblasts but does not bind to the glycosaminoglycan residues of heparan
      sulfate proteoglycans.
AB  - We have investigated the proposal that the receptor-associated protein (RAP) of
      the low density lipoprotein receptor-related protein/alpha 2-macroglobulin
      receptor binds to heparan sulfate proteoglycans (HSP). 125I-RAP binds to two
      sites on the surface of fibroblasts as follows: a high affinity site with a Kd of
      1.4 nM and a low affinity site (Kd = 188 nM) with a capacity of more than 1000
      fold the maximum amount of lipoprotein receptor-related protein/alpha 2
      macroglobulin receptor on the cell surface. 125I-RAP binding to the low affinity
      site was abolished by heparin or Suramin. However, maximal digestion of the
      glycosaminoglycan chains of HSP with heparinase or culturing the cells in
      chlorate, an inhibitor of proteoglycan sulfation, did not affect the binding of
      125I-RAP or of 125I-labeled, methylamine-activated alpha 2-macroglobulin.
      Comparison of 125I-RAP degradation at two different concentrations suggests that
      the low affinity, high capacity site on the surface of human fibroblasts
      participates in the endocytosis of 125I-RAP. The nature of the low affinity site
      remains to be elucidated, but we can exclude the glycosaminoglycan chains of HSP.

PMID- 7515053
TI  - Localization of vitronectin binding domain in plasminogen activator inhibitor-1.
AB  - Plasminogen activator inhibitor type 1 (PAI-1) is the rapid physiologic inhibitor
      of tissue-type plasminogen activator and urokinase-type plasminogen activator
      (uPA). In plasma and the extracellular matrix, PAI-1 is associated with the
      adhesive glycoprotein vitronectin. In order to characterize the PAI-1 structural
      domain responsible for binding to vitronectin, the segment of the PAI-1 cDNA
      encoding amino acids 13-147 (nucleotides 248-650) was randomly mutagenized and
      subcloned into a bacterial expression vector containing the mature PAI-1 coding
      sequence. Recombinant PAI-1 mutants were expressed in Escherichia coli and
      bacterial lysates assayed in duplicate for uPA inhibitory activity and
      vitronectin binding. Of 190 clones screened, six consistently demonstrated
      decreased vitronectin binding relative to uPA inhibitory activity. DNA sequence
      analysis of four of these clones identified 10 unique missense mutations, all
      located between base pairs 298 and 641, with each clone containing between one
      and four substitutions. Each substitution was expressed independently by site
      directed mutagenesis and again analyzed for uPA inhibitory activity and
      vitronectin binding. Five point mutations that selectively disrupt vitronectin
      binding were identified. All 5 residues are located on the exterior of the PAI-1
      structure. These findings appear to define a complex binding surface that bridges
      alpha-helices C and E to beta-strand 1A and includes amino acids 55, 109, 110,
      116, and 123. These results suggest that vitronectin binding may stabilize the
      active conformation of PAI-1 by restricting the movement of beta-sheet A and
      thereby preventing insertion of the reactive center loop.

PMID- 7515054
TI  - Substrate specificity of Fpg protein. Recognition and cleavage of oxidatively
      damaged DNA.
AB  - The 8-oxoguanine-DNA glycosylase of Escherichia coli, also known as
      formamidopyrimidine-DNA glycosylase (Fpg protein), has N-glycosylase and AP-lyase
      activities. This enzyme repairs oxidative DNA damage by efficiently removing
      formamidopyrimidine lesions and 8-oxoguanine residues from DNA. Defined
      oligodeoxynucleotides containing various 8-oxopurines were used to examine the
      substrate specificity of Fpg protein and to establish the role of functional
      groups in DNA on damage recognition and catalysis. Binding affinities of Fpg
      protein were established for duplex oligodeoxynucleotides containing 8-oxo-2'
      deoxyguanine, 8-oxo-2'-deoxyadenine, 8-oxo-2'-deoxynebularine, 8-oxo-2'
      deoxyinosine, abasic sites, and a ring-open adduct of C8-aminofluorene guanine.
      The C8 keto group of 8-oxodG:dC presents in the major groove and is correlated
      with tight binding (Kd = 8.9 nM). Binding is much weaker when the C8 keto
      functional group is in the minor groove, as in 8-oxodG:dA (Kd = 340 nM). Km and
      Vmax were determined for the cleavage reaction. Specificity constants (Kcat/Km)
      are consistently higher for oligodeoxynucleotide duplexes containing 8-oxopurines
      with C6 and C8 keto groups, as in 8-oxodG:dC and 8-oxodI:dC, where Kcat/Km are
      9.3 and 18 min-1 nM x 10(-3), respectively. 8-oxodN:dC lacks the C6 keto group;
      the specificity constant is 0.024 min-1 nM x 10(-3). Taken together, our data
      suggest that the C8 keto group of 8-oxodeoxyguanine and the carbonyl moiety of
      formamidopyrimidine enable Fpg protein to recognize and bind duplex DNA
      containing these modified bases. An enzyme-catalyzed reaction involving the C6
      keto group of the substrate leads to removal of these lesions. A mechanism
      involving protonation at O-6 of 8-oxoguanine is proposed to account for the N
      glycosylase activity of this enzyme.

PMID- 7515055
TI  - Subunit-selective mutagenesis of Glu-89 residue in human immunodeficiency virus
      reverse transcriptase. Contribution of p66 and p51 subunits to nucleoside analog
      sensitivity, divalent cation preference, and steady state kinetic properties.
AB  - The E89G alteration in the human immunodeficiency virus type 1 reverse
      transcriptase has been shown to confer resistance to nucleoside analogs and a
      loss of magnesium cation preference (Prasad, V.R., Lowy, I., De Los Santos, T.,
      Chiang, L., and Goff, S.P. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 11363-11367.
      The wild type reverse transcriptase heterodimer, chimeric reverse transcriptases
      that contain the E89G alteration in one of the subunits (p66wt/p51m and
      p66m/p51wt), and the mutant enzyme (p66m/p51m) were prepared. Analysis of steady
      state kinetic parameters showed that the mutant enzyme (p66m/p51m) displayed a
      higher Vmax, a higher Km for 2'-deoxythymidine triphosphate, and a higher Ki for
      2',3'-dideoxythymidine triphosphate than the wild type enzyme. The increased Km
      and Ki values were observed only when a heterodimer contained the alteration in
      the p66 subunit. Tests for divalent cation requirement showed that only the
      dimers containing the wild type p66 (p66wt/p51wt and p66wt/p51m) displayed a
      preference for magnesium. Our results indicate that p66 plays a dominant role in
      deoxynucleotide triphosphate substrate recognition (Km), nucleoside analog
      sensitivity (Ki), and magnesium preference. However, the increased Vmax displayed
      by the mutant enzyme (p66m/p51m) appeared to be determined by both of the
      subunits.

PMID- 7515056
TI  - Differential phylogenetic footprinting as a means to identify base changes
      responsible for recruitment of the anthropoid gamma gene to a fetal expression
      pattern.
AB  - Expression of the anthropoid (simian) gamma gene in fetal life contrasts with the
      exclusively embryonic expression pattern of the gamma-like genes of other
      eutherian mammals. To elucidate the factors responsible for this change in
      expression pattern, we utilized a strategy called differential phylogenetic
      footprinting (DPF). This strategy entails the following: (a) identification,
      within regulatory regions, of the gamma promoter, of individual nucleotides that
      differ between human (fetal expression), and galago (embryonic expression) gamma
      genes, (b) analysis of the effect of these nucleotide differences on the binding
      of nuclear proteins to human and galago sequences, and (c) assessment of the
      functional consequences of these binding changes in expression assays. The DPF
      analysis revealed several proteins that bind upstream from the CCAAT motif in the
      galago gamma promoter but do not bind to the corresponding region of the human
      gamma promoter. In transfection assays, binding of these proteins is associated
      with erythroid-specific repression of promoter strength. Binding sites for these
      proteins also occur near the CCAAT box of other embryonically expressed genes,
      including rabbit, mouse, and dwarf lemur gamma genes and the human epsilon globin
      gene. These data are consistent with the hypothesis that sequence changes near
      the proximal CCAAT box in the ancestral simian gamma gene may have facilitated a
      novel expression pattern by reducing the binding of repressors that act in the
      fetal stage.

PMID- 7515057
TI  - A splice variant of arrestin. Molecular cloning and localization in bovine
      retina.
AB  - Inactivation of photolyzed rhodopsin requires phosphorylation of the receptor and
      binding of the 48-kDa regulatory protein arrestin. We recently isolated a novel
      form of arrestin, termed p44, that is truncated at the COOH terminus (Palczewski,
      K., Buczylko, J., Ohguro, H., Annan, R. S., Carr, S. A., Crabb, J. W., Kaplan, M.
      W., Johnson, R. S., and Walsh, K. A. (1994) Protein Sci. 3, 319-329) and strongly
      inhibits Gt activation by non-phosphorylated rhodopsin. p44 is identical to
      arrestin except at the COOH terminus, where the 35 amino acids of arrestin are
      replaced by a single alanine residue. p44 is identified as a splice variant of
      arrestin based on the identical cDNA sequence of p44 with arrestin (except the 3'
      non-coding regions), the presence of an exon/intron junction at the Ser369 codon,
      and identical Southern hybridization patterns generated by the 3' non-coding
      portion of arrestin and p44. Immunocytochemistry reveals that p44 is localized in
      the photoreceptor outer segment, whereas arrestin is present throughout the cell.
      This specificity of localization to the outer segment is consistent with a role
      of p44 in the phototransduction cascade.

PMID- 7515058
TI  - Suppression of antioxidative enzyme expression by transforming growth factor-beta
      1 in rat hepatocytes.
AB  - We have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1)
      and three cytokines on expression of antioxidative enzymes, manganese-superoxide
      dismutase, copper, zinc-superoxide dismutase, and catalase in cultured
      hepatocytes of rat. While interleukin-1 beta and interleukin-6 induced manganese
      superoxide dismutase gene expression, they slightly suppressed catalase gene
      expression in rat hepatocytes. TGF-beta 1 suppressed expression of all these
      antioxidative enzymes in time- and cell density-dependent manners. Furthermore,
      we examined the effect of TGF-beta 1 on expression of glutathione peroxidase and
      glutathione-S-transferase, which exhibit glutathione-dependent peroxidase
      activity in rat hepatocytes. Expression of two major classes of the rat
      glutathione-S-transferase subunits 1 and 2 was also reduced by TGF-beta 1,
      although expression of glutathione peroxidase was not affected. Flow cytometric
      analysis indicated that production of peroxides was increased in hepatocytes
      treated with TGF-beta 1. These data suggest that augmented production of hydrogen
      peroxide and its intermediate through suppression of antioxidative enzyme
      expression may participate in cellular injury or growth inhibition promoted by
      TGF-beta 1.

PMID- 7515059
TI  - Regulation of human dihydrodiol dehydrogenase by Michael acceptor xenobiotics.
AB  - A human oxidoreductase (H-37) that is overexpressed in ethacrynic acid-resistant
      HT29 colon cells (Ciaccio, P. J., Stuart, J.E., and Tew, K.D. (1993) Mol.
      Pharmacol. 43, 845-853) has been identified as a dihydrodiol dehydrogenase.
      Translated protein from a dihydrodiol dehydrogenase cDNA isolated from a library
      prepared from ethacrynic acid-resistant HT29 cell poly(A+) RNA was recognized by
      anti-H-37 IgG and was identical in molecular weight with H-37. The isolated cDNA
      was identical in both nucleotide and amino acid sequences with the recently
      cloned liver dihydrodiol dehydrogenase (Stolz, A., Hammond, L., Lou, H.,
      Takikawa, H., Ronk, M., and Shively, J.E. (1993) J. Biol. Chem. 268, 10448
      10457). Using this cDNA as probe, we have examined its induction by Michael
      acceptors. The steady state dihydrodiol dehydrogenase mRNA level in the
      ethacrynic acid-resistant line was increased 30-fold relative to that of wild
      type cells. Twenty-four hour treatment of wild-type cells with ethacrynic acid or
      dimethyl maleate increased mRNA 10-fold and 5-fold, respectively. These changes
      are accompanied by both increased protein expression and increased NADP-dependent
      1-acenaphthenol oxidative activity in cell cytosol. In gel shift assays, compared
      to wild type controls, increased binding of NAD(P)H quinone oxidoreductase human
      antioxidant response element (hARE) DNA to redox labile protein complexes present
      in treated and resistant cell nuclear extract was observed. Ethacrynic acid
      induced CAT activity 2-fold in Hepa1 cells stably transfected with NAD(P)H
      quinone oxidoreductase hARE-tk-CAT chimeric gene construct. Thus, dihydrodiol
      dehydrogenase protein is inducible by de novo synthesis from mRNA by structurally
      related monofunctional inducer Michael acceptors. Altered in vitro binding of
      nuclear protein to the hARE is indirect evidence for the involvement of an
      element similar to hARE in the regulation of dihydrodiol dehydrogenase by these
      agents.

PMID- 7515061
TI  - Molecular dissection of ligand binding sites on the low density lipoprotein
      receptor-related protein.
AB  - The low density lipoprotein receptor-related protein (LRP) is a large
      multifunctional receptor that is involved in the cellular uptake of a number of
      functionally diverse ligands including apoE-rich remnant lipoproteins,
      lipoprotein lipase, alpha 2-macroglobulin-protease complexes, plasminogen
      activator-inhibitor complexes, and the active protease tissue-type plasminogen
      activator. Ligand binding and competition experiments suggest that most LRP
      ligands bind to specific, independent sites on the large 515-kDa subunit of the
      receptor. In a previous study (Moestrup, S.K., Holtet, T.L., Etzerodt, M.,
      Thogersen, H.C., Nykjaer, A., Andreasen, P.A., Rasmussen, H.H., Sottrup-Jensen,
      L., and Gliemann, J. (1993) J. Biol. Chem. 268, 13691-13696), ligand blotting was
      used to localize the binding sites for urokinase-type plasminogen activator
      plasminogen activator inhibitor-1 (PAI-1) complexes and for alpha 1-macroglobulin
      to a proteolytic fragment of LRP containing the second cluster of complement-type
      cysteine-rich repeats. Here, we have used a recombinant DNA approach to express
      functionally restricted chimeric "LRP-minireceptors" containing two different
      regions of the extracellular domain of the receptor in cultured cells. Receptor
      associated protein, a negative modulator of LRP activity, is bound and
      internalized by cells transfected with either construct. A minireceptor
      containing the cluster of eight complement-type cysteine-rich repeats followed by
      four epidermal growth factor precursor homologous domains binds and internalizes
      125I-labeled plasminogen activator-PAI-1 complexes. It also mediates the cellular
      uptake of the uncomplexed protease tissue-type plasminogen activator (tPA),
      suggesting that the tPA and PAI-1 binding sites on LRP are in close vicinity and
      might promote cooperative binding of tPA-PAI-1 complexes. However, alpha 2
      macroglobulin is not internalized by this minireceptor suggesting that this
      ligand requires the presence of a single epidermal growth factor-repeat which is
      contained in the previously studied proteolytic fragment but is absent from the
      minireceptor.

PMID- 7515063
TI  - Regulation of c-Fgr protein kinase by c-Src kinase (CSK) and by polycationic
      effectors.
AB  - The protein tyrosine kinase expressed by the protooncogene c-fgr is
      phosphorylated and down-regulated in vitro by the c-Src kinase (CSK). CSK
      catalyzed phosphorylation affects Tyr-511 of c-Fgr, homologous to Tyr-527 of c
      Src and it prevents the autophosphorylation normally occurring at c-Fgr Tyr-400,
      homologous to c-Src Tyr-416. Polylysine, histones H1 and H2A and other
      polycationic proteins on the other hand stimulate c-Fgr activity while promoting
      enhanced autophosphorylation of both Tyr-400 and Tyr-511. Once phosphorylated at
      Tyr-511 and down-regulated by CSK, c-Fgr is no more susceptible to polylysine
      stimulation. Previous autophosphorylation (at Tyr-400) reduces c-Fgr
      susceptibility to down-regulation by CSK, although Tyr-511 can be still
      phosphorylated by it. If a more exhaustive autophosphorylation (of both Tyr-400
      and Tyr-511) is performed in the presence of polylysine, c-Fgr becomes totally
      insensitive to CSK down-regulation. These data support the concept that down
      regulation of c-Fgr by Tyr-511 phosphorylation is prevented if Tyr-400 is also
      phosphorylated and they are consistent with an outcompetition of phospho-Tyr-511
      from the Src homology 2 domain by phospho-Tyr-400, which, in c-Fgr, is surrounded
      by an amino acid sequence divergent from that of the other Src-related protein
      tyrosine kinases.

PMID- 7515064
TI  - Localization of functionally important epitopes within the second C-type domain
      of coagulation factor V using recombinant chimeras.
AB  - Coagulation factor V, an integral component of the prothrombinase complex,
      possesses two C-type domains at the carboxyl-terminal end of the molecule.
      Homologous C-type domains are present in factor VIII as well as several non
      coagulation proteins. Deletion of the second C-type domain of factor V results in
      the loss of procoagulant activity and the ability to bind phosphatidylserine. We
      now report the effect of substitution of all or a portion of the C2 domain of
      factor V with the corresponding regions of factor VIII or the human breast
      carcinoma protein BA46. Substitution of the entire domain with a heterologous C2
      domain does not restore significant procoagulant activity, although smaller, exon
      size substitutions do result in chimeras with partial activity (approximately 10%
      of factor Va). Using chimeras with partial substitutions, we determined that the
      amino-terminal region of the domain is involved in binding to phosphatidylserine.
      In contrast, the central region of the domain is not involved in
      phosphatidylserine binding, but an antibody binding at or near this site inhibits
      procoagulant activity, suggesting that this region is involved in a separate
      function. Lastly, the molecular basis for the light chain doublet, which is
      important in the expression of full procoagulant activity, is located within the
      carboxyl-terminal region of the C2 domain.

PMID- 7515060
TI  - ATF3 and ATF3 delta Zip. Transcriptional repression versus activation by
      alternatively spliced isoforms.
AB  - ATF3 is a member of the mammalian activating transcription factor/cAMP responsive
      element binding protein (ATF/CREB) family of transcription factors. In this
      report, we demonstrate that, contrary to the implication of its name, ATF3
      represses rather than activates transcription from promoters with ATF sites. We
      also present evidence suggesting that one possible mechanism by which ATF3
      represses transcription is to stabilize inhibitory co-factors at the promoter. In
      addition, we describe a naturally occurring, alternatively spliced, form of ATF3:
      ATF3 delta Zip. ATF3 delta Zip lacks the leucine zipper domain and does not bind
      to DNA. In contrast to ATF3, ATF3 delta Zip stimulates transcription, presumably
      by sequestering inhibitory co-factors away from the promoter. It is possible that
      ATF3 delta Zip is a physiologically important regulator and that it, together
      with ATF3, regulates the expression of specific target genes.

PMID- 7515066
TI  - In vitro and ribosome-bound folding intermediates of P22 tailspike protein
      detected with monoclonal antibodies.
AB  - It remains unclear whether polypeptide chains renaturing in vitro from strong
      denaturants proceed through the same folding pathway as chains released from
      ribosome within cells. Folding intermediates formed both in vivo and in vitro
      have been examined using three monoclonal antibodies shown previously to
      recognize different epitopes of the native P22 tailspike protein (Friguet, B.,
      Djavadi-Ohaniance, L., Haase-Pettingell, C. A., King J., and Goldberg, M. E.
      (1990) J. Biol. Chem. 265, 10347-10351). The tailspike protein was reconstituted
      from polypeptide chains unfolded by urea as described by Fuchs et al. (Fuchs, A.,
      Seiderer, C., and Seckler, R. (1991) Biochemistry 30, 6598-6604), and the
      appearance of immunoreactive forms during the refolding was monitored. The three
      antibodies discriminated intermediates at different stages in the folding
      pathway. On the basis of the reconstitution pathway determined from spectroscopic
      and hydrodynamic measurements by Fuchs et al. (1991), monoclonal antibody (mAb)
      236-3 recognized partially folded monomers, mAb 155-3 recognized folded protomers
      in a protrimer species, and mAb 33-2 recognized the native trimer. The kinetics
      of appearance of the immunoreactive forms during the in vitro refolding of the
      protein in crude extracts of phage-infected cells was similar to that observed
      with the pure tailspike. Thus, the antibodies provided probes for the chain
      folding and association pathway in vivo. The conformation of the ribosome-bound
      tailspike polypeptide chains of the infected cells was analyzed with the three
      antibodies. The antibodies recognizing native trimer and the protrimer did not
      bind chains associated with the ribosomes. Antibody 236-3, which recognized
      structured monomers in vitro, bound to the polypeptide chains still associated
      with ribosomes. This result suggests that steps that take place in solution
      during in vitro refolding may occur in a ribosome-bound state in vivo.

PMID- 7515062
TI  - Dephosphorylation of insulin receptor substrate 1 by the tyrosine phosphatase
      PTP2C.
AB  - The phosphotyrosine (Tyr(P)) form of insulin receptor substrate 1 (IRS-1) is a
      key component in insulin signaling. Our previous study revealed that Tyr(P) IRS-1
      binds to the widely distributed tyrosine phosphatase PTP2C through the src
      homology 2 (SH2) domains of the latter. In the present study, we examined the
      activity of this enzyme and of a truncated form lacking the SH2 domains (delta
      PTP2C) toward IRS-1 and also toward the cytoplasmic domain of the insulin
      receptor. Tyr(P) IRS-1 was prepared by phosphorylation of recombinant IRS-1 with
      recombinant cytoplasmic insulin receptor kinase (CIRK). PTP2C rapidly
      dephosphorylated Tyr(P) IRS-1; dephosphorylation by delta PTP2C was approximately
      one-third as fast. Other substrates, including Tyr(P) CIRK, were not
      dephosphorylated as rapidly by PTP2C; moreover, delta PTP2C was at least 10 times
      more active than PTP2C toward CIRK and other substrates. These results indicate
      that the binding of Tyr(P) residues on IRS-1 to the SH2 domain(s) of PTP2C
      enhances its activity toward IRS-1 and suggest that PTP2C is the phosphatase
      responsible for the dephosphorylation of IRS-1 in vivo. In addition, with the
      expectation that a PTP2C-resistant form of IRS-1 will be useful in investigations
      of IRS-1 function, we determined that IRS-1 can be thiophosphorylated with
      adenosine 5'-O-(3-thiotriphosphate) and CIRK and that this form of IRS-1 is
      resistant to PTP2C.

PMID- 7515065
TI  - Insulin and interleukin-1 differentially regulate pp63, an acute phase
      phosphoprotein in hepatoma cell line.
AB  - We have reported previously that the phosphoprotein pp63, an acute phase protein,
      which has been recently identified as the rat fetuin, was capable of blocking the
      mitogenic effect of insulin on the rat Fao hepatoma cell line, without affecting
      metabolic effects of the hormone. Only the phosphorylated form of the protein has
      been shown to exhibit both anti-tyrosine kinase and growth inhibitory properties.
      In this study, we used the FTO-2B rat hepatoma cell line to analyze the
      mechanisms involved in the control of synthesis and/or phosphorylation of pp63.
      For this purpose, we investigated the action of effectors known to modulate
      hepatic functions, such as cytokines (interleukin (IL)-1 beta and IL-6), which
      regulate the production of acute phase proteins, and insulin, which elicits
      profound effects on hepatocyte metabolism. Here, we demonstrate that IL-1 beta
      diminished markedly the pp63 production by affecting its mRNA transcription and
      that the cytokine was able to modify the N-glycosylation process of the protein.
      In contrast, insulin did not affect the biosynthesis of pp63 but dramatically
      decreased its extent of phosphorylation.

PMID- 7515067
TI  - Local macromolecular extravasation in thermal burns quantified by fluorescent
      video microscopy and computer vision.
AB  - A dorsal skin flap chamber model was developed for analysis of the microvascular
      response to moderate intensity local thermal burns. Fluorescein isothiocyanate
      tagged 70,000 d dextran was introduced to visualize the extravasation and
      interstitial transport of macromolecules at the burn site. Contact burns 0.5 cm
      in diameter were affected by touching a thermostated metal rod onto the exposed
      epidermal side of the chamber preparation. All burns were of 5-second duration at
      temperatures between 55 degrees C and 70 degrees C. Postburn leakage of the
      fluorescein-labeled probed was monitored at numerous sites in the preparation on
      a fluorescent microscope equipped with a low-light-level intensified silicon
      intensified target video camera and recorded on tape for subsequent quantitative
      analysis. Selected scenes were digitized and subjected to a sequence of computer
      image processing operations to extract quantitative information about the
      concentration distribution and net accumulation of dextran in the interstitial
      space as a function of postburn time. A diffusion model based on cylindrical
      geometry was fit to the concentration profile data at each site analyzed, and an
      apparent diffusion coefficient describing the interstitial transport process was
      determined. The interstitial transport increased with burn temperature up to a
      threshold of 70 degrees C, where other factors resulted in significant reduction
      in the loss of fluorescent macromolecule from the vasculature.

PMID- 7515069
TI  - The induction of 72-kD gelatinase in T cells upon adhesion to endothelial cells
      is VCAM-1 dependent.
AB  - T cell extravasation from the bloodstream into the perivascular tissue during
      inflammation involves transmigration through the endothelial cell layer and
      basement membrane into the interstitial matrix. The specific mechanisms by which
      T cells transmigrate, however, are poorly understood. Matrix degradation by
      enzymes such as 72-kD gelatinase has been implicated as an important component in
      tissue invasion by various types of cells. In this study, we have demonstrated
      that 72-kD gelatinase is induced in T cells upon adhesion to endothelial cells.
      We also provide evidence that the induction of 72-kD gelatinase is mediated by
      binding to vascular cell adhesion molecule-1 (VCAM-1). The T cells used in this
      study were cloned murine Th1 cells antigenic to myelin basic protein. These cells
      express very late antigen-4 on their cell surface and have been shown to
      infiltrate the brain parenchyma and cause experimental autoimmune
      encephalomyelitis when infused into normal mice (Baron, J. L., J. A. Madri, N. H.
      Ruddle, G. Hashim, and C. A. Janeway. 1993. J. Exp. Med. 177:57-68). In the
      experiments presented here, T cells were cocultured with VCAM-1-positive and 
      negative endothelial cells grown in a monolayer in order to study the expression
      of 72-kD gelatinase upon T cell adhesion. Additional experiments were conducted
      in which T cells were cocultured with VCAM-1 positive cells grown on microporous
      membranes suspended in transwells to study 72-kD gelatinase following T cell
      transmigration. T cells were also incubated with recombinant VCAM-1 in order to
      study the role of VCAM-1 in inducing 72-kD gelatinase. The results demonstrated
      that T cells adhered to both VCAM-1-positive and -negative endothelial cells. T
      cells that adhered to the VCAM-1-positive endothelial cells exhibited an
      induction in 72-kD gelatinase protein, activity, and mRNA whereas 72-kD
      gelatinase was not induced in the T cells that adhered to the VCAM-1-negative
      endothelial cells. Incubating T cells with recombinant VCAM-1 coated onto tissue
      culture plastic showed that T cells adhered to the molecule and that adhesion to
      recombinant VCAM-1 was sufficient to induce 72-kD gelatinase. Further, T cells
      that had transmigrated through a VCAM-1-positive endothelial cell monolayer
      exhibited 72-kD gelatinase activity but not mRNA expression. In addition, 72-kD
      gelatinase was detected on the cell surface of the transmigrated T cells by FACS
      analysis. In other experiments, TIMP-2 was added to the transmigration studies
      and was shown to reduce T cell transmigration.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7515068
TI  - KIF3A is a new microtubule-based anterograde motor in the nerve axon.
AB  - Neurons are highly polarized cells composed of dendrites, cell bodies, and long
      axons. Because of the lack of protein synthesis machinery in axons, materials
      required in axons and synapses have to be transported down the axons after
      synthesis in the cell body. Fast anterograde transport conveys different kinds of
      membranous organelles such as mitochondria and precursors of synaptic vesicles
      and axonal membranes, while organelles such as endosomes and autophagic
      prelysosomal organelles are conveyed retrogradely. Although kinesin and dynein
      have been identified as good candidates for microtubule-based anterograde and
      retrograde transporters, respectively, the existence of other motors for
      performing these complex axonal transports seems quite likely. Here we
      characterized a new member of the kinesin super-family, KIF3A (50-nm rod with
      globular head and tail), and found that it is localized in neurons, associated
      with membrane organelle fractions, and accumulates with anterogradely moving
      membrane organelles after ligation of peripheral nerves. Furthermore, native
      KIF3A (a complex of 80/85 KIF3A heavy chain and a 95-kD polypeptide) revealed
      microtubule gliding activity and baculovirus-expressed KIF3A heavy chain
      demonstrated microtubule plus end-directed (anterograde) motility in vitro. These
      findings strongly suggest that KIF3A is a new motor protein for the anterograde
      fast axonal transport.

PMID- 7515070
TI  - Postnatal growth and mental development: evidence for a "sensitive period".
AB  - For many years it has been suspected that severely impaired somatic growth during
      early postnatal life can be associated with the subsequent impairment of mental
      abilities. This study aimed to test that hypothesis on the basis of data gathered
      from a prospective whole population survey of infant development in south London.
      A year's birth cohort of 1558 full-term singletons was monitored; 47 otherwise
      healthy cases with serious growth faltering in the first year were recruited.
      Mental and psychomotor abilities were assessed at 15 months. Potentially
      confounding psychosocial variables, including cognitive stimulation received at
      home, were measured contemporaneously. A statistical model was constructed that
      enabled the timing, duration and severity of growth faltering to be used as
      predictors of mental functioning. Up to 37% of the variance in cognitive and
      psychomotor outcome at 15 months can be explained by the model. The first few
      postnatal months appear to constitute a "sensitive period" for the relationship
      between growth and mental development.

PMID- 7515071
TI  - Bioavailability of gamma-globulin after subcutaneous infusions in patients with
      common variable immunodeficiency.
AB  - Replacement therapy, using subcutaneous infusions of gamma-globulin, is being
      applied increasingly for antibody-deficient patients, as this form of treatment
      has been found to be related to a very low frequency of adverse systemic
      reactions. However, the uptake of IgG from subcutaneous tissue may be low, owing
      to degradation locally, especially for the IgG3 molecule. Therefore, the kinetics
      of IgG and IgG-subclass concentrations in the sera of 23 patients with common
      variable immunodeficiency was investigated during 18 months of subcutaneous
      infusions of gamma-globulin (100 mg/kg/week). Seventeen patients were previously
      treated with intramuscular injections or intravenous infusions. The mean serum
      IgG level increased twice in the previously treated patients and four times in
      the previously untreated patients. A steady state was reached after 6 months if
      the subcutaneous infusions were given weekly and after 1 week if the patients
      were given daily infusions for 5 consecutive days and, thereafter, weekly
      infusions. The fractional catabolic rate of IgG (4.1-5.9% per day) was found to
      be at the lower limit reported for normal controls, if 100% bioavailability of
      the infused IgG was assumed. The fractional contents of IgG subclasses in the
      patients' serum IgG resembled the physiological pattern, with the exception of
      IgG4, which was not present in the gamma-globulin preparations used.
      Significantly increased levels of IgG1 and -2 were seen in both previously
      treated and untreated patients during the treatment.

PMID- 7515072
TI  - Rapid diagnosis of early ectopic pregnancy in an emergency gynaecology service-
      are measurements of progesterone, intact and free beta human chorionic
      gonadotrophin helpful?
AB  - The clinical usefulness of measuring serum concentrations of progesterone, human
      chorionic gonadotrophin (HCG) and the free beta-subunit of HCG in distinguishing
      between early viable and non-viable pregnancy, before an accurate ultrasound
      diagnosis is possible, was evaluated in a prospective study of patients
      presenting to our emergency gynaecology service with a clinical suspicion of
      ectopic pregnancy. Patients were selected on the basis of initial HCG
      concentrations; samples with HCG 25-10,000 IU/l were later analysed for
      progesterone and free beta HCG. Of the 181 patients studied, 38 (21%) had an
      ectopic pregnancy, 108 (60%) had a spontaneous abortion and 35 (19%) had a viable
      intra-uterine pregnancy. Concentrations of HCG and free beta HCG in the group
      with viable pregnancies were significantly higher than in the group with ectopic
      pregnancy (P < 0.001) and than those destined to miscarry (P < 0.01).
      Progesterone concentrations were also significantly higher in the viable versus
      the ectopic and the spontaneous abortion groups (P < 0.001 in each case). Despite
      these highly significant differences there was a degree of overlap such that it
      was impossible to devise a cut-off level for any hormone analysed, either singly
      or in combination, which would offer a clinically useful predictor of outcome.

PMID- 7515073
TI  - Artificial induction of the acrosome reaction in human spermatozoa.
AB  - This study investigated the use of human follicular fluid and pentoxifylline as
      inducers of the human sperm acrosome reaction in vitro. Motile sperm suspensions
      were prepared using a discontinuous Percoll gradient, preincubated for 3 h,
      divided into aliquots and exposed to various concentrations of non-heat
      inactivated follicular fluid for 1 and 24 h and pentoxifylline for 30 min.
      Detection of the acrosome reaction involved the combined use of a fluorescent
      vital stain, H33258, and fluorescein isothiocyanate-conjugated peanut agglutinin
      (FITC-PNA). A short (1 h) exposure to follicular fluid at concentrations of 50%
      or more, did not compromise sperm motility and significantly increased the
      proportion of spermatozoa having completed the acrosome reaction. Similarly, a 30
      min exposure to pentoxifylline also significantly increased the proportion of
      spermatozoa having completed the acrosome reaction.

PMID- 7515075
TI  - Indicators of developmental and functional status of Mexican-American and Puerto
      Rican children.
AB  - The overall purpose of this study was to describe the developmental and
      functional status of young Latino children. We analyzed data from the Hispanic
      Health and Nutrition Examination Survey and estimated the percentages of young
      Mexican-American and mainland Puerto Rican children with indicators of
      developmental need for special services, i.e., low birth weight, use of neonatal
      intensive care, congenital problems, chronic conditions of developmental concern,
      functional limitations, and physician diagnoses of medical conditions. Estimates
      suggest that Puerto Rican children had substantially poorer status than Mexican
      American children who, in turn, have indicators that are comparable with those
      reported for the general population. The difference in status between the two
      Latino groups merits further investigation.

PMID- 7515074
TI  - Detection of anti-human immunodeficiency virus type 1 (HIV-1) immunoglobulin G in
      urine by an ultrasensitive enzyme immunoassay (immune complex transfer enzyme
      immunoassay) with recombinant reverse transcriptase as an antigen.
AB  - Anti-human immunodeficiency virus type 1 immunoglobulin G in urine was detected
      by an immunoassay with reverse transcriptase as the antigen and beta-D
      galactosidase as the label; this immunoassay was 30-fold more sensitive than the
      previous immunoassay with peroxidase as the label. The sensitivity and
      specificity were both 100%. The lowest signal for asymptomatic carriers was 20
      fold higher than the highest signal for seronegative subjects.

PMID- 7515076
TI  - Pediatricians' approaches to developmental problems: has the gap been narrowed?
AB  - Whether recent advances in developmental pediatrics have influenced pediatric
      practice is uncertain. We interviewed, in their offices, 41 randomly selected,
      board-certified, primary care pediatricians in Connecticut to explore their
      attitudes and clinical approaches to developmental problems. Responses were
      compared with those from a similar survey of 97 New England pediatricians
      performed 15 years ago. Important changes in certain clinical approaches were
      found. For example, pediatricians are currently less likely to rely on history
      and physical examination alone to confirm a suspicion of mental retardation (p <
      .01) and are more likely to refer such a child for further assessment (p < .01);
      they are more likely to perform hearing screening in evaluating a child with
      delayed speech (p < .05); they are more likely to contact the school in
      evaluating a failing child (p < .01), and are more likely to refer such a child
      for further assessment (p < .01). Results indicate favorable changes in
      pediatricians' approaches to developmental problems and support the greater
      emphasis on developmental issues in pediatric education.

PMID- 7515077
TI  - Very low birth weight infants (< 1501 g) at double risk.
AB  - This study examines the outcome at ages 2 and 3 years of very-low-birth-weight
      infants (N = 105) at double risk. Double risk was defined with reference to
      Fagan's model of intelligence. According to this model, cognitive-processing
      ability and culturally provided information produce knowledge. The Fagan Test of
      Infant Intelligence was used to assess processing ability, whereas parental
      socioeconomic status (SES) was used as an indicator of available information.
      Knowledge was measured by means of well-known psychometric tests of young
      children's abilities. Children at double risk were consistently delayed with
      respect to knowledge of intellectual skills and language as compared with
      children who were not at double risk. The data suggest that the assessment of
      processing ability and parental SES may provide a better foundation for detecting
      developmental delay than does a medical main-effect model.

PMID- 7515078
TI  - Organization of the efferent projections from the pontine parabrachial area to
      the bed nucleus of the stria terminalis and neighboring regions: a PHA-L study in
      the rat.
AB  - The organization of efferent projections from the pontine parabrachial (pPB) area
      to the forebrain rostral to the central nucleus of the amygdala (Ce) was studied
      in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin (PHA
      L), into subregions of the pPB area. The present study is a follow-up of a former
      study (Bernard et al. [1993] J. Comp. Neurol. 329:201-229) which examines pPB
      projections onto the Ce. The results demonstrate that: (1) the pPB(m) region (the
      medial, the ventral lateral subnuclei and the waist area) diffusely projects to
      the lateral division (BSTL) of the bed nucleus of the stria terminalis (BST), the
      Ce-BSTL continuum (including, the dorsal portion of substantia innominata, the
      ventral portion of globus pallidus, the fundus striatum, and the substriatal
      area) and to a lesser extent the agranular insular cortex; (2) the pPB(1) region
      [the central lateral (pPBcl) and the outer portion of external lateral subnuclei]
      densely projects to the dorsal lateral subnucleus of BST (BSTdl); only the pPBcl
      subnucleus projects to the median, the anteroventral and the periventricular
      nuclei of the preoptic hypothalamus; and (3) the remaining pPB area (the dorsal
      lateral, part of the external lateral and the external medial subnuclei) projects
      to the nucleus of horizontal limb of diagonal band but does not project onto the
      BST and the preoptic hypothalamus. It is suggested that the pPB(m)-BSTL "diffuse
      pathway" is mainly implicated in motivational and autonomic aspects of taste. The
      pPB(1)-BSTdl and hypothalamic "concentrated pathways" could be implicated in
      autonomic and nociceptive processes.

PMID- 7515079
TI  - Morphology of two classes of target-specific bullfrog sympathetic preganglionic
      neurons.
AB  - These experiments took advantage of the unique ability to define target-specific
      sympathetic preganglionic neurons in the bullfrog spinal cord in order to examine
      the morphologies of different classes of preganglionic neurons. Sympathetic
      preganglionic neurons were identified by retrograde transport of fast blue from
      the sympathetic chain. Subsequently, fast blue-labelled sympathetic preganglionic
      neurons in fixed spinal cord slices were filled with lucifer yellow and processed
      for visualization with lucifer yellow antiserum, biotinylated secondary
      antiserum, and avidin peroxidase. Target specificity of sympathetic preganglionic
      neurons was determined by anatomical position; sympathetic preganglionic neurons
      that control the vasculature (C-type sympathetic preganglionic neurons) lie in a
      position caudal to those that control nonvascular targets [B-type sympathetic
      preganglionic neurons; Horn and Stofer (1988) J. Comp. Neurol. 268:71]. These two
      classes of sympathetic preganglionic neurons have qualitatively similar
      morphologies. However, they exhibit significant quantitative differences in total
      dendritic length and the rostrocaudal extent of dendrites. These differences are
      likely to be associated with differences in the number of synapses received by
      these two classes of sympathetic preganglionic neurons. Moreover, the segmental
      control of sympathetic preganglionic neurons by descending brainstem projections
      is likely to be finer for those involved in vascular control than for those that
      influence other targets.

PMID- 7515080
TI  - Regeneration of axons into the trochlear rootlet after anterior medullary lesions
      in the rat is specific for ipsilateral IVth nerve motoneurones.
AB  - The fibre projection from the IVth nerve nucleus to the superior oblique muscle
      was determined quantitatively in the normal rat by defining fibre numbers in
      transverse sections of the IVth nerve, and neurone numbers after retrograde
      labelling by horseradish peroxidase (HRP) injection into the muscle. There were
      183 +/- 27 (S.E.) labelled neurones in the nucleus contralateral to the injected
      muscle and only 2 +/- 1 ipsilateral. The ipsilateral fibre number was 234 +/- 7
      and the cell/axon ratio 0.8 +/- 0.1. Extensive analysis of all HRP retrogradely
      labelled material revealed no central fibre contribution to the IVth nerve other
      than from neurones resident in the trochlear nucleus. The central portion of the
      trochlear nerve tract was severed at its point of decussation in the anterior
      medullary velum. Ninety days after lesion, 10 +/- 4 (6% of control) neurones were
      labelled in the ipsilateral trochlear nucleus; none were labelled in the
      contralateral nucleus or in any other part of the midbrain, pons, medulla, or
      cerebellum. The number of myelinated fibres in the IVth nerve had decreased to 21
      +/- 5 (9% of control) so that the cell/axon ratio was 0.4 +/- 0.2, thus
      suggesting that a single motoneurone has more fibres after lesion. In electron
      micrographs of the IVth nerve, larger than normal numbers of unmyelinated fibres
      were seen. Many myelinated fibres displayed signs of abnormal myelination. After
      regeneration, the projection was exclusively ipsilateral and not crossed as in
      the normal. These findings establish that there is a high degree of specificity
      after regeneration since no myelinated central nervous system axons other than
      trochlear fibres select the IVth nerve root as a trajectory over which to
      regenerate.

PMID- 7515081
TI  - Interconnections between the prefrontal cortex and the premotor areas in the
      frontal lobe.
AB  - We examined interconnections between a portion of the prefrontal cortex and the
      premotor areas in the frontal lobe to provide insights into the routes by which
      the prefrontal cortex gains access to the primary motor cortex and the central
      control of movement. We placed multiple injections of one retrograde tracer in
      the arm area of the primary motor cortex to define the premotor areas in the
      frontal lobe. Then, in the same animal, we placed multiple injections of another
      retrograde tracer in and around the principal sulcus (Walker's area 46). This
      double labeling strategy enabled us to determine which premotor areas are
      interconnected with the prefrontal cortex. There are three major results of this
      study. First, we found that five of the six premotor areas in the frontal lobe
      are interconnected with the dorsolateral prefrontal cortex. Second, the major
      site for interactions between the prefrontal cortex and the premotor areas is the
      ventral premotor area. Third, the prefrontal cortex is interconnected with only a
      portion of the arm representation in three premotor areas (supplementary motor
      area, the caudal cingulate motor area on the ventral bank of the cingulate
      sulcus, and the dorsal premotor area), whereas it is interconnected with the
      entire arm representation in the ventral premotor area and the rostral cingulate
      motor area. These observations indicate that the output of the prefrontal cortex
      targets specific premotor areas and even subregions within individual premotor
      areas.

PMID- 7515082
TI  - Development and organization of the ocular motor nuclei in the larval sea
      lamprey, Petromyzon marinus L.: an HRP study.
AB  - Retrograde transport of horseradish peroxidase (HRP) after its application into
      the orbit was used to investigate the development of the different ocular motor
      nuclei in larvae of the sea lamprey (Petromyzon marinus) and to identify their
      regions of origin. In the smallest larvae studied (10-19 mm in length), the
      oculomotor and abducens neurons were ipsilateral to the site of HRP application,
      whilst trochlear neurons were contralateral. These motoneurons did not have
      dendritic processes. In larvae more than 19 mm in length, both ipsilateral and
      contralateral components were found in the oculomotor and trochlear nuclei;
      dendrites were present, and their length and branching increased with larval age.
      An adult-like pattern of topographic organization and dendritic arborization was
      reached in larvae of about 45-60 mm in length. In oculomotor neurons, medial
      dendrites appear first, then dorsolateral dendrites, and finally ventral
      dendrites. Similarly, in trochlear neurons ventral and ventrolateral dendrites
      develop first, followed by dorsal dendrites that course either to the caudal
      optic tectum or to the terminal fields of the octaval and lateral line nerves in
      the cerebellar plate. Dorsal and ventral dendrites of the abducens neurons arise
      at the same time, but dorsal dendrites attain an adult-like morphology earlier. A
      few motoneurons showed ventricular attachments in larvae longer than 40 mm. The
      significance of these processes and their possible usefulness as a marker for the
      regions of origin of the ocular motor nuclei are discussed. Finally, the results
      presented here indicate that differentiation of the ocular motor nuclei in larval
      lampreys precedes and is independent of the maturation of the eye at
      transformation.

PMID- 7515084
TI  - Impaired endothelium-dependent vasodilation in patients with essential
      hypertension: evidence that the abnormality is not at the muscarinic receptor
      level.
AB  - OBJECTIVES: The purpose of this study was to determine whether the impaired
      endothelium-dependent vasodilation of hypertensive patients is related to a
      specific defect of the muscarinic receptor or to a broader abnormality of the
      vascular endothelium. BACKGROUND: Patients with essential hypertension have
      abnormal endothelium-dependent vasodilator response to acetylcholine. However,
      whether this results from an isolated dysfunction of the endothelial cell
      muscarinic receptor is unknown. METHODS: The responses of the forearm vasculature
      to acetylcholine and substance P (endothelium-dependent agents acting on
      different receptors) and to sodium nitroprusside (a direct dilator of vascular
      smooth muscle) were studied in eight hypertensive patients (six men, two women;
      mean age [+/- SD] 50 +/- 12 years) and eight normal control subjects (four men,
      four women; mean age 49 +/- 9 years). To determine the nitric oxide contribution
      to substance P-induced vasodilation, the vascular responses to substance P were
      also measured after inhibition of nitric oxide synthesis with NG-monomethyl-L
      arginine. Drugs were infused into the brachial artery, and forearm blood flow was
      measured by strain gauge plethysmography. RESULTS: The response to acetylcholine
      was significantly blunted in hypertensive patients (highest blood flow [mean +/-
      SD] 8.4 +/- 4 vs. 13.8 +/- 4 ml/min per 100 ml in control subjects, p < 0.03).
      Similarly, the vasodilator effect of substance P was significantly reduced in
      hypertensive patients (highest blood flow [mean +/- SD] 8.8 +/- 4 vs. 13.9 +/- 4
      ml/min per 100 ml in control subjects, p < 0.03). A significant correlation was
      found between the maximal blood flow with acetylcholine and that with substance P
      (r = 0.68, p < 0.004). The vasodilator response to sodium nitroprusside was
      similar in patients and control subjects. The nitric oxide contribution to
      substance P-induced vasodilation was reduced in hypertensive patients, such that
      the responses to substance P measured during infusion of NG-monomethyl-L-arginine
      were not significantly different between the two groups. CONCLUSIONS: These
      findings indicate that the endothelial abnormality of patients with essential
      hypertension is not restricted to the muscarinic cell receptor.

PMID- 7515083
TI  - The rostral dorsal cap and ventrolateral outgrowth of the rabbit inferior olive
      receive a GABAergic input from dorsal group Y and the ventral dentate nucleus.
AB  - The dorsal cap and ventrolateral outgrowth of the inferior olive are involved in
      the control of eye movements. The caudal dorsal cap is predominantly involved in
      the horizontal optokinetic reflex; it receives most of its GABAergic input from
      the nucleus prepositus hypoglossi. In the present study, we determined the source
      of a major inhibitory input to the rostral dorsal cap and the ventrolateral
      outgrowth, which are the olivary subnuclei mainly involved in the "vertical"
      optokinetic reflexes. We studied these subnuclei in the rabbit with the use of
      retrograde tracing of horseradish peroxidase and anterograde tracing of wheat
      germ agglutinin-coupled horseradish peroxidase combined with postembedding
      immunocytochemistry. The ventral dentate nucleus of the cerebellum and dorsal
      group y project contralaterally to the rostral dorsal cap and ventrolateral
      outgrowth; this projection is entirely GABAergic. The terminals of this input
      form predominantly symmetric synapses with extraglomerular and intraglomerular
      dendrites; the remaining terminals are axosomatic. In addition, the dorsal cap
      and ventrolateral outgrowth contain significantly more crest synapses than any
      other olivary subnucleus. The terminals that form these crest synapses are
      derived from dorsal group y and/or the ventral dentate nucleus. None of the
      terminals in the dorsal cap or ventrolateral outgrowth was glycinergic.

PMID- 7515085
TI  - Radioimmunoassay versus flow cytometric assay to quantify LPS-binding protein
      (LBP) concentrations in human plasma.
AB  - LPS-binding protein (LBP) is an acute phase protein present in plasma, that has
      been shown to play a major role in sensitizing monocytes to LPS. We describe here
      two assays to quantify LBP in plasma. The first assay made use of monophosphoryl
      lipid A to capture LBP in human plasma, and LBP was detected by radiolabeled anti
      LBP IgG. The second assay measured LBP by flow cytometry, using LBPs ability to
      present LPS to the CD14 receptor present on monocytes. Both assays had a similar
      level of sensitivity, that allowed the quantification of LBP in human plasma.

PMID- 7515086
TI  - A novel bioactivity assay for monoclonal antibodies directed against IgE.
AB  - A novel bioactivity assay has been developed to quantitate the biological
      activity of a humanized, monoclonal anti-IgE antibody (rhuMAbE25) in human whole
      blood. Heparinized blood specimens from prescreened healthy donors were
      sensitized for 2 h with a constant amount of human plasma containing IgE specific
      for ragweed and then challenged with ragweed allergen. Histamine was released in
      a dose-dependent fashion and reached plateau levels after 30 min. As expected,
      the release of histamine by ragweed allergen was time, temperature and Ca2+
      dependent, and could be enhanced by the presence of 33% deuterium oxide. Allergen
      triggered release could be inhibited by rhuMAbE25 with an effective dose range
      from 0.1 to 1 microgram/ml. Preincubation with other humanized MAbs, which
      exhibit 95% homology to rhuMAbE25 but differ in epitope specificity, failed to
      inhibit the ragweed-induced histamine release. Overall, this bioactivity assay
      has a low interassay variability (%CV) of 17% (n = 23) and can be readily
      modified to determine if rhuMAbE25 or other anti-allergy therapeutics are capable
      of blocking histamine release elicited by other allergens. Moreover, the assay
      can be used to confirm IgE-mediated allergic responses and to provide early
      information regarding safety and potential efficacy of therapeutics aimed at
      blocking IgE dependent responses.

PMID- 7515087
TI  - Recombinant single-chain antibody peptide conjugates expressed in Escherichia
      coli for the rapid diagnosis of HIV.
AB  - Recombinant single chain Fv (scFv) antibody fragments can form the basis of a
      rapid, whole-blood diagnostic assay. The scFv described in this study is derived
      from a monoclonal antibody which has a high affinity for glycophorin A, an
      abundant glycoprotein on the human red blood cell membrane surface. The prototype
      reagent built around the scFv was designed to detect, in whole blood samples, the
      presence of antibodies that have arisen through infection with a foreign organism
      such as human immunodeficiency virus. The scFv was composed of the antibody heavy
      chain variable domain (Vh) joined by a 15 residue linker -(GGGGS)3- to the light
      chain variable domain (V1) terminated by either a C-terminal octapeptide tail
      (FLAG) or a 35 amino acid segment from the gp41 surface glycoprotein of HIV-1.
      Constructs were cloned into a Escherichia coli expression vector, pHFA, and
      expressed in a soluble form into culture supernatant. The product retained anti
      glycophorin activity which could be detected directly in culture supernatants by
      ELISA. Furthermore, the scFv-epitope fusion functioned efficiently in the whole
      blood agglutination assay and was able to distinguish between HIV-1 positive and
      negative sera.

PMID- 7515090
TI  - A subcloned ribosomal RNA probe for bacterial ribotype analysis.

PMID- 7515088
TI  - Measurement of adhesion molecule expression on neutrophils and fixation.

PMID- 7515092
TI  - Acute necrotizing pancreatitis induced by a CDE diet in the rat: a morphologic
      and functional study.
AB  - We studied the effect on the rat pancreas of a choline-deficient diet
      supplemented with ethionine administered over different time periods. The study
      was carried out in several groups of male Wistar rats weighing 300 gm and fed for
      60, 104, 195, 250, and 336 hours with a choline-deficient diet supplemented with
      ethionine (CDE). Analysis of pure exocrine pancreatic secretion in animals fed
      the CDE for 60 hours revealed a decrease in total protein, amylase, and trypsin
      as compared with animals fed a standard diet. After cholecystokinin stimulation,
      a gradual decrease in secretion was observed as the duration of the CDE was
      increased, such that after 336 hours no response to cholecystokinin was found,
      indicating the lack of pancreatic functionality. Analysis of pancreas
      preparations by light microscopy showed the existence of infiltration, edema, and
      hemorrhagic foci after 60 hours of CDE administration. As the duration of the
      treatment increased, pancreatic morphology deteriorated, with the appearance of
      vacuolization and foci of necrosis at 195 hours. This deterioration became more
      pronounced after 250 to 336 hours, progressing to a considerable degree of
      hemorrhage and necrosis of the acinar tissue. These results clearly confirm the
      existence of acute necrotizing and hemorrhagic pancreatitis in rats fed a CDE for
      250 to 336 hours.

PMID- 7515089
TI  - Heat-shock mannoproteins as targets of secretory IgA in Candida albicans.
AB  - The expression of Candida albicans antigenic determinants reacting with secretory
      IgA from patients with oral and vaginal candidiasis was investigated under
      different in vitro conditions. Reversible antigenic transitions were inducible in
      synthetic medium by temperature shifts, as the yeast cells were positive by an
      indirect immunofluorescence assay after being incubated at 37 degrees C but not
      at 25 degrees C. In vitro temperature-inducible C. albicans antigenic
      determinants reactive with secretory IgA were characterized by radioimmune
      Western blot as mannoproteins with molecular masses of 180-200, 130-150, 90-110,
      and 60-70 kDa. This is the first report on the expression of mannoproteins
      regulated by temperature involved in the secretory immune response during mucosal
      candidiasis.

PMID- 7515094
TI  - Comparison of biological responses of human monocytes and THP-1 cells to
      chemokines of the intercrine-beta family.
AB  - The biological responses of human monocytes and cells of the monomyelocytic THP-1
      cell line to stimulation with members of the beta chemokine family are described
      in this report. All three chemokines tested, MCP-1, MIP-1 alpha, and RANTES,
      elicited mobilization of intracellular free calcium in monocytes and THP-1 cells.
      The magnitude of response was highest with MCP-1 stimulation. MCP-1 desensitized
      monocyte responses to MIP-1 alpha and RANTES, but no such desensitization was
      observed in THP-1 cells. MIP-1 alpha or RANTES did not desensitize either
      monocytes or THP-1 cells to MCP-1 stimulation. All three chemokines elicited a
      potent chemotactic response in monocytes that was comparable in magnitude to that
      of f-Met-Leu-Phe. MIP-1 alpha and RANTES required a fivefold higher dose than MCP
      1 to elicit a peak response. On the contrary, THP-1 cells showed no significant
      chemotactic response. Studies of the desensitization of the monocyte chemotactic
      response indicated that all three chemokines are capable of causing complete
      homologous desensitization. Heterologous desensitization was observed only when
      monocytes were treated with MCP-1 followed by MIP-1 alpha or RANTES. Studies of
      actin polymerization and cell polarization responses of monocytes indicated that
      these two responses attained peak magnitude after 10 min of stimulation with any
      of the chemokines. Dose-response kinetics were similar to those of the
      chemotactic response. THP-1 cells again failed to show either of these two
      responses. Finally, the activation potential of the chemokines was measured by
      their ability to induce respiratory burst. A tenfold higher concentration than
      that causing peak chemotactic response was required to elicit respiratory burst
      and no heterologous desensitization was noticed. Respiratory burst could be
      induced in THP-1 cells with a direct protein kinase C activator but not with any
      of the chemokines. These results indicate that, of the three examples tested, MCP
      1 is the most potent member of the beta chemokine family in the biological
      responses examined. Although a calcium response was elicited in THP-1 cells with
      chemokines, a lack of subsequent responses indicates some missing links in the
      downstream signal transduction pathways.

PMID- 7515093
TI  - Quantitation of soluble fibrinogen binding to platelets by fluorescence-activated
      flow cytometry.
AB  - Soluble fibrinogen binding to agonist-stimulated blood platelets is the essential
      physiologic function of the glycoprotein IIb-IIIa (GPIIb-IIIa) receptor. We
      describe a method of quantifying this receptor-ligand interaction by using flow
      cytometry to detect the binding of fluorescein-labeled fibrinogen to activated
      platelets. Fibrinogen conjugated with fluorescein isothiocyanate (FITC-FGN) was
      structurally and functionally indistinguishable from native fibrinogen when
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, thrombin
      clottability, and receptor affinity studies. Platelet samples, at a concentration
      of 2 x 10(7) ml, were incubated with FITC-FGN and activated with adenosine
      diphosphate (ADP) before cytometric acquisition of fluorescence and scatter data.
      ADP-induced binding of soluble FITC-FGN to platelet GPIIb-IIIa was specific, time
      dependent, and saturable. Cytometric analysis of FITC calibration beads allowed
      generation of standard curves relating bead fluorescence intensity to the number
      of fluorescein equivalents per bead. With this information, platelet fluorescence
      intensity was converted into the number of FITC-FGN molecules bound per platelet.
      Such quantitative analysis of fibrinogen binding yielded a dissociation constant
      of 2.48 +/- 0.5 x 10(-7) mol/L and a maximum fibrinogen binding capacity of 42,
      124 +/- 5, 628 molecules per platelet (mean +/- SEM), which are comparable to
      published results with radioligand assays. The simplicity, sensitivity, and
      quantifiability of this method may make it a useful technique for basic and
      clinical research involving GPIIb-IIIa function.

PMID- 7515095
TI  - P-selectin-dependent leukocyte recruitment and intestinal mucosal injury induced
      by lactoferrin.
AB  - Plasma concentrations of lactoferrin relevant to an inflammatory response are
      known to elicit leukocyte-endothelial cell adhesion in mesenteric venules. The
      objectives of this study were (1) to determine whether exogenously administered
      lactoferrin causes microvascular and mucosal injury in rat intestine and (2) to
      assess the contribution of adherent leukocytes to a lactoferrin-mediated injury
      process. Mucosal myeloperoxidase (MPO) activity and vascular protein clearance
      were monitored in the distal intestine of male Sprague-Dawley rats. Macroscopic
      erosive lesions of the mucosa and increases in mucosal MPO and intestinal
      vascular protein were observed 2 h following the lactoferrin infusion, results
      consistent with granulocyte accumulation and microvascular protein leakage. These
      lactoferrin-induced alterations were significantly attenuated in animals
      pretreated with a monoclonal antibody (mAb) directed against P-selectin but not
      by an E-selectin-specific mAb. In another series of experiments, leukocyte
      adherence/emigration and leakage of fluorescein isothiocyanate (FITC)-labeled
      albumin were measured in rat mesenteric venules using intravital video
      microscopy. Lactoferrin elicited increases in both leukocyte adhesion/emigration
      and albumin extravasation, which were attenuated by mAbs directed against P
      selectin but not E-selectin. These observations indicate that (1) the lactoferrin
      released by activated neutrophils may lead to significant microvascular and
      mucosal injury or dysfunction and (2) the lactoferrin-induced injury is related
      to P-selectin-mediated adhesion of leukocytes to microvascular endothelium. Our
      results raise the possibility that neutrophil-derived lactoferrin contributes to
      the inflammatory response by promoting further granulocyte accumulation and
      activation and that mAbs to P-selectin may be therapeutically beneficial in
      inflammatory disorders.

PMID- 7515096
TI  - Differential effects of cAMP-elevating drugs on stimulus-induced cytosolic
      calcium changes in human basophils.
AB  - Drugs that elevate cAMP levels in human basophils are known to inhibit
      immunoglobulin E (IgE)-mediated histamine release. We have examined whether cAMP
      active agents inhibit the cytosolic Ca2+, [Ca2+]i, response that normally
      accompanies activation of basophils. As previously described, this [Ca2+]i
      response is biphasic, one phase dependent on internal sources of calcium and a
      second later phase dependent on extracellular calcium, as observed in many cell
      types. Forskolin and rolipram or their combination had no effect on the initial
      elevation of cytosolic calcium that follows stimulation with anti-IgE antibody.
      In contrast, the second phase of the IgE-mediated calcium response was inhibited
      by these agents. For IgE-mediated responses, the relative efficacy of various
      cAMP active agents (rolipram approximately forskolin < dibutyryl cAMP < forskolin
      + rolipram) for the inhibition of histamine release and the second-phase calcium
      response was similar and roughly paralleled the measured increase in basophil
      cAMP. In contrast, neither the first nor the second phase of the f-Met-Leu-Phe
      (fMLP)-induced calcium response was inhibited by any of the cAMP-active agents
      tested. Indeed, at low concentrations of fMLP, a combination of forskolin and
      rolipram caused slight enhancement of the calcium response. This result was
      consistent with the observations that these agents had no effect or caused slight
      enhancement of histamine or leukotriene released induced by fMLP. Similarly, cAMP
      active agents caused no inhibition of C5a or phorbol ester (phorbol myristate
      acetate)-induced histamine release. These observations suggest that inhibition of
      the phase of the calcium response that is dependent on extracellular calcium
      could account for the inhibition of histamine release by these agents. However,
      these studies also suggested that (1) this is effect is not exerted at the level
      of the inositol trisphosphate (InsP3) receptor or InsP3 metabolism and (2) the
      mechanisms that maintain the second-phase calcium response are possibly distinct
      for IgE- and fMLP-mediated reactions because cAMP-active agents inhibited the
      second-phase response of only one stimulus.

PMID- 7515091
TI  - Nitric oxide in pancreatic secretion and hormone-induced pancreatitis in rats.
AB  - The aim of the present study was to determine the role of endogenous nitric oxide
      (NO) in pancreatic secretion in vivo and amylase release from pancreatic acini in
      vitro and in caerulein-induced acute pancreatitis in rats. Blockade of NO
      synthase by NG-nitro-L-arginine (L-NNA) (2.5 mg/kg i.v.) significantly reduced
      basal pancreatic protein secretion and that induced by the infusion of CCK (0.5
      micrograms/kg-h), feeding, and the diversion of pancreatic juice in rats with
      pancreatic fistula. This inhibitory effect was partially reversed when L-arginine
      (50 mg/kg-h i.v.) was added to L-NNA. L-Arginine alone (50 mg/kg i.v.) did not
      affect basal or caerulein-induced pancreatic secretion. L-NNA, L-arginine, or
      their combination added in various concentrations to the incubation medium of
      dispersed acini failed to affect basal or secretagogue (caerulein or urecholine)
      stimulated amylase release. Infusion of caerulein (5 micrograms/kg-h) for 5 h
      produced histological changes of acute edematous pancreatitis accompanied by a
      marked increase in pancreatic protein content and about 50% reduction in tissue
      blood flow. L-NNA alone also reduced the pancreatic blood flow and caused a
      significant increase in pancreatic weight and protein content. L-NNA
      significantly potentiated the inflammatory changes in the pancreas caused by
      caerulein. Addition of L-arginine enhanced the pancreatic blood flow and
      ameliorated the pancreatitis induced by caerulein alone or that combined with L
      NNA. We conclude that NO is involved in the stimulation of pancreatic secretion
      in vivo and exhibits a beneficial effect on pancreatitis, probably by improving
      the pancreatic blood flow.

PMID- 7515097
TI  - CD50 (intercellular adhesion molecule 3) stimulation induces calcium mobilization
      and tyrosine phosphorylation through p59fyn and p56lck in Jurkat T cell line.
AB  - The leukocyte differentiation antigen, CD50, has been recently identified as the
      intercellular adhesion molecule 3 (ICAM-3), the third counter-receptor of
      leukocyte function-associated antigen 1 (LFA-1). This molecule seems to be
      specially involved in the adhesion events of the initial phases of the immune
      response. To characterize the role of CD50 in leukocyte interactions, the
      different molecular events induced after cross-linking of CD50 on T cell-derived
      Jurkat cell line have been analyzed. When cells were incubated with anti-CD50
      mAbs and cross-linked with polyclonal goat anti-mouse immunoglobulins, a rise in
      intracellular calcium concentration ([Ca2+]i) was observed. This increase in
      [Ca2+]i was mainly due to the uptake of extracellular Ca2+. This Ca2+ flux
      involved tyrosine phosphorylations and was further increased by CD3
      costimulation. These data, together with those obtained by phosphotyrosine (P
      Tyr) immunoprecipitation and in vitro kinase assays, suggested the involvement of
      protein-tyrosine kinases (PTK) in CD50 transduction pathways. By using specific
      antisera, the presence of p56lck and p59fyn protein tyrosine kinases (PTK) was
      clearly demonstrated in the CD50 immunoprecipitates. These findings suggest that
      the interaction of CD50 with its natural ligand (LFA-1) may result in T
      lymphocyte activation events, in which CD50 could play a very active role after
      antigen triggering.

PMID- 7515098
TI  - Induction of programmed cell death in human hematopoietic cell lines by
      fibronectin via its interaction with very late antigen 5.
AB  - Extracellular matrix (ECM) molecules such as fibronectin (FN), collagens, and
      laminin have important roles in hematopoiesis. However, little is known about the
      precise mechanisms by which ECM molecules regulate proliferation of human
      hematopoietic progenitor cells. In this study, we have investigated the effects
      of ECM molecules, particularly of FN, on the proliferation of a myeloid leukemia
      cell line, M07E, which proliferates in response to either human
      granulocyte/macrophage colony-stimulating factor (GM-CSF) or stem cell factor
      (SCF). The [3H]thymidine incorporation and cell enumeration assays showed that FN
      strikingly inhibited GM-CSF- or SCF-induced proliferation of M07E cells in a dose
      dependent manner, whereas little or no inhibition was induced by collagen types I
      and IV. The growth suppression of M07E cells was not due to the inhibitory effect
      of FN on ligand binding or very early events in the signal transduction pathways
      from the GM-CSF or SCF receptors. DNA content analysis using flow cytometry after
      staining with propidium iodide revealed that the treatment of M07E cells with FN
      did not block the entry of the cells into the cell cycle after stimulation with
      GM-CSF or SCF, whereas the treatment resulted in the appearance of subdiploid
      peak. Furthermore, FN was found to induce oligonucleosomal DNA fragmentation and
      chromatin condensation in the cells even in the presence of GM-CSF or SCF,
      suggesting the involvement of programmed cell death (apoptosis) in the FN-induced
      growth suppression. The growth suppression or apoptosis induced by FN was rescued
      by the addition of either anti-FN antibody, anti-very late antigen 5 monoclonal
      antibody (anti-VLA5 mAb), or GRGDSP peptide, but not by that of anti-VLA4 mAb or
      GRGESP peptide, suggesting that the FN effects on M07E cells were mediated
      through VLA5. In addition, the FN-induced apoptosis was detectable in VLA5
      positive human hematopoietic cell lines other than M07E cells, but not in any of
      the VLA5-negative cell lines. These results suggest that FN is capable of
      inducing apoptosis via its interaction with VLA5, and also raise the possibility
      that the FN-VLA5 interaction may contribute, at least in part, to negative
      regulation of hematopoiesis.

PMID- 7515099
TI  - Role of kit-ligand in proliferation and suppression of apoptosis in mast cells:
      basis for radiosensitivity of white spotting and steel mutant mice.
AB  - The receptor tyrosine kinase Kit and its cognate ligand KL/steel factor are
      encoded at the white spotting (W) and Steel (Sl) loci of the mouse, respectively.
      Mutations at both the W and the Sl loci affect hematopoiesis including the stem
      cell hierarchy, erythropoiesis, and mast cells, as well as gametogenesis and
      melanogenesis. In addition, mutant mice display an increased sensitivity to
      lethal doses of irradiation. The role of KL/c-kit in cell proliferation and
      survival under conditions of growth factor-deprivation and gamma-irradiation was
      studied by using bone marrow-derived mast cells (BMMC) as a model. Whereas
      apoptosis induced by growth factor deprivation in BMMC is a stochastic process
      and follows zero order kinetics, gamma-irradiation-induced apoptosis is an
      inductive process and follows higher order kinetics. In agreement with these
      results, gamma-irradiation-induced apoptosis in BMMC was shown to be dependent on
      p53 whereas apoptosis induced by deprivation is partly dependent on p53, implying
      that there are other mechanisms mediating apoptosis in KL-deprived BMMC. In the
      presence and in the absence of serum, KL stimulated proliferation by promoting
      cell cycle progression. The presence of KL was required only during the early
      part of the G1 phase for entry into the S phase. At concentrations lower than
      those required for proliferation, KL suppressed apoptosis induced by both growth
      factor-deprivation and gamma-irradiation, and internucleosomal DNA fragmentation
      characteristic of apoptosis. The ability of KL to suppress apoptosis was
      independent of the phase of the cell cycle in which the cells were irradiated and
      suppression of apoptosis was a prerequisite for subsequent cell cycle
      progression. Moreover, addition of KL to gamma-irradiated and growth factor
      deprived cells could be delayed for up to 1 h after irradiation or removal of
      growth factors when cells became irreversibly committed to apoptosis. KL and IL-3
      induce suppression of apoptosis in mast cells by different mechanisms based on
      the observations of induction of bcl-2 gene expression by IL-3 but not by KL. It
      is proposed that the increased sensitivity of W and Sl mutant mice to lethal
      irradiation results from paucity of the apoptosis suppressing and proliferative
      effects of KL.

PMID- 7515100
TI  - The Src-family kinase, Fyn, regulates the activation of phosphatidylinositol 3
      kinase in an interleukin 2-responsive T cell line.
AB  - The proliferation of antigen-activated T cells is mediated by the T cell-derived
      growth factor, interleukin 2 (IL-2). The biochemical signaling cascades
      initiating IL-2-induced growth are dependent upon protein tyrosine kinase (PTK)
      activity. One IL-2-regulated PTK implicated in this cascade is the Src-family
      kinase, Fyn. Previous studies have described a physical association between Fyn
      and a potential downstream substrate, phosphatidylinositol 3-kinase (PI3-kinase)
      as well as the IL-2-dependent activation of PI3-kinase in T cells; however, the
      role of Fyn in IL-2-induced PI3-kinase activation remains unclear. In this
      report, we demonstrate that IL-2 stimulation triggers tyrosine phosphorylation of
      the p85 subunit of PI3-kinase in the murine T cell line, CTLL-2. Lysates prepared
      from growth factor-deprived and IL-2-stimulated T cells reconstituted both the
      binding of CTLL-2 cell-derived Fyn to and the IL-2-inducible tyrosine
      phosphorylation of exogenously added recombinant p85. Furthermore, overexpression
      of wild-type Fyn in these cells enhanced both the basal and IL-2-mediated
      activation of PI3-kinase. Additional studies of the Fyn-PI3-kinase interaction
      demonstrated that the Src homology 3 (SH3) domain of Fyn constitutes a direct
      binding site for the p85 subunit of PI3-kinase. These results support the notion
      that Fyn may be directly involved in the activation of the downstream signaling
      enzyme, PI3-kinase, in IL-2-stimulated T cells.

PMID- 7515101
TI  - Adeno-associated virus 2-mediated high efficiency gene transfer into immature and
      mature subsets of hematopoietic progenitor cells in human umbilical cord blood.
AB  - Recombinant adeno-associated virus 2 (AAV) virions were constructed containing a
      gene for resistance to neomycin (neoR), under the control of either the
      herpesvirus thymidine kinase (TK) gene promoter (vTK-Neo), or the human
      parvovirus B19 p6 promoter (vB19-Neo), as well as those containing an upstream
      erythroid cell-specific enhancer (HS-2) from the locus control region of the
      human beta-globin gene cluster (vHS2-TK-Neo; vHS2-B19-Neo). These recombinant
      virions were used to infect either low density or highly enriched populations of
      CD34+ cells isolated from human umbilical cord blood. In clonogenic assays
      initiated with cells infected with the different recombinant AAV-Neo virions,
      equivalent high frequency transduction of the neoR gene into slow-cycling
      multipotential, erythroid, and granulocyte/macrophage (GM) progenitor cells,
      including those with high proliferative potential, was obtained without
      prestimulation with growth factors, indicating that these immature and mature
      hematopoietic progenitor cells were susceptible to infection by the recombinant
      AAV virions. Successful transduction did not require and was not enhanced by
      prestimulation of these cell populations with cytokines. The functional activity
      of the transduced neo gene was evident by the development of resistance to the
      drug G418, a neomycin analogue. Individual high and low proliferative colony
      forming unit (CFU)-GM, burst-forming unit-erythroid, and CFU-granulocyte
      erythroid macrophage megakaryocyte colonies from mock-infected, or the
      recombinant virus-infected cultures were subjected to polymerase chain reaction
      analysis using a neo-specific synthetic oligonucleotide primer pair. A 276-bp DNA
      fragment that hybridized with a neo-specific DNA probe on Southern blots was only
      detected in those colonies cloned from the recombinant virus-infected cells,
      indicating stable integration of the transduced neo gene. These studies suggest
      that parvovirus-based vectors may prove to be a useful alternative to the more
      commonly used retroviral vectors for high efficiency gene transfer into slow or
      noncycling primitive hematopoietic progenitor cells, without the need for growth
      factor stimulation, which could potentially lead to differentiation of these
      cells before transplantation.

PMID- 7515102
TI  - CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid
      dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins
      including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD
      tyrosine phosphorylated protein.
AB  - CD40 plays an important role in B cell activation, proliferation, and Ig class
      switching. The signal transduction pathway mediated by CD40 was studied using
      monoclonal antibody (mAb) 626.1 to CD40. Burkitt's lymphoma and Epstein-Barr
      virus-transformed B cell lines and tonsilar B lymphocytes were treated with the
      anti-CD40 mAb for various lengths of time. The early events triggered by CD40
      were examined by monitoring the changes in tyrosine phosphorylation of cellular
      proteins with anti-phosphotyrosine mAb. Dephosphorylation of specific proteins
      ranging between 50-110 kD and the appearance of a 28-kD tyrosine phosphorylated
      protein were seen within 30 s in human B cell lines. The dephosphorylation was
      reversed and the 28-kD protein was dephosphorylated in cells stimulated for 1
      min. In resting B cells, the appearance of the 28-kD phosphoprotein was observed
      in 30 s after the addition of the anti-CD40 mAb. The tyrosine phosphorylation of
      this protein persisted. The patterns of protein tyrosine phosphorylation differed
      from those induced by an anti-immunoglobulin M mAb. The changes in the state of
      tyrosine phosphorylation induced by the anti-CD40 mAb were obviated by mAb to
      CD45, a protein tyrosine phosphatase (PTP) or by the addition of sodium
      orthovanadate, a broad PTP inhibitor. They were also blocked by protein tyrosine
      kinase (PTK) inhibitors, herbimycin A and genistein, and PKC and protein
      serine/threonine kinase inhibitors, H7 and HA1004. In addition, the alteration in
      the tyrosine phosphorylation of PTKs Lyn, Fyn, and Syk was directly demonstrated.
      Engagement of CD40 for 30 s induced a transient decrease in tyrosine
      phosphorylation of these PTKs. These results indicate that the early events in
      CD40 signaling involve the complex interaction between PTP and protein kinases.

PMID- 7515106
TI  - Exonic trinucleotide repeats and expression of androgen receptor gene in spinal
      cord from X-linked spinal and bulbar muscular atrophy.
AB  - We studied exonic trinucleotide repeats and expression of androgen receptor (AR)
      gene in the spinal cord from an autopsied patient with X-linked spinal and bulbar
      muscular atrophy (SBMA). Forty-nine CAG triplet repeats were found in tissues
      from the spinal cord, cerebrum, cerebellum, cardiac muscle and bladder, while
      there were 20-24 CAG repeats in these tissues from control subjects, consisting
      of three patients with amyotrophic lateral sclerosis (ALS) and three patients
      with lung cancer. Thus, mitotic instability of the AR gene in SBMA may not occur
      at the level of somatic cells. To determine whether expression of the AR gene in
      the spinal cord of SBMA differs from that in control subjects, we used
      quantitative reverse transcriptase (RT)-PCR and Western blot. AR mRNA and protein
      were detected in the spinal cord from the patient with SBMA, but the levels of
      both AR mRNA and protein were less than those from the patients with ALS in whom
      the loss of motor neurons was similar to findings in the patient with SBMA. These
      findings suggest that structural alteration plus a reduced level of AR in the
      spinal cord are involved in the pathogenesis of SBMA, resulting in degeneration
      of motor neurons.

PMID- 7515103
TI  - Amino acid residues that flank core peptide epitopes and the extracellular
      domains of CD4 modulate differential signaling through the T cell receptor.
AB  - Hen egg lysozyme 52-61-specific CD4+ T cells responded by interleukin 2 (IL-2)
      secretion to any peptide containing this epitope regardless of length of NH2- and
      COOH-terminal composition. However, CD4- variants could only respond to peptides
      containing the two COOH-terminal tryptophans at positions 62 and 63.
      Substitutions at these positions defined patterns of reactivity that were
      specific for individual T cells inferring a T cell receptor (TCR)-based
      phenomenon. Thus, the fine specificity of major histocompatibility complex (MHC)
      peptide recognition by the TCR was dramatically affected by CD4 and the COOH
      terminal peptide composition. Peptides that failed to induce IL-2 secretion in
      the CD4- variants nevertheless induced strong tyrosine phosphorylation of CD3
      zeta. Thus, whereas the TCR still recognized and bound to the MHC class II
      peptide complex resulting in protein phosphorylation, this interaction failed to
      induce effective signal transduction manifested by IL-2 secretion. This provides
      a clear example of differential signaling mediated by peptides known to be
      naturally processed. In addition, the external domains of CD4, rather than its
      cytoplasmic tail, were critical in aiding TCR recognition of all peptides derived
      from a single epitope. These data suggest that the nested flanking residues,
      which are present on MHC class II but not class I bound peptides, are
      functionally relevant.

PMID- 7515107
TI  - On teaching bedside diagnostic and therapeutic procedures to medical students: an
      annotated bibliography of audiovisual materials.
AB  - OBJECTIVE: The teaching of procedures that involve risk of pain or morbidity
      deserves special care. The author set out to develop a teaching program for
      medical students to ensure quality control of bedside diagnostic and therapeutic
      procedures. DESIGN: A bibliography of available videotapes and related
      audiovisual teaching materials on 15 common bedside procedures was assembled
      following requests for materials from all U.S. medical schools. Audiovisual
      materials from nine institutions were reviewed. SETTING: Medical schools and
      teaching institutions. PARTICIPANTS: Medical schools and libraries. MAIN RESULTS:
      Seventy-three percent (24/33) of responding schools had no visual material on the
      procedures. There was ten times more material on physical diagnosis than on
      bedside procedures. About 20 videotapes were reviewed in an annotated
      bibliography. Some videos contained valuable insights on how to make good
      teaching materials. A set of criteria for quality videotapes is listed.
      CONCLUSIONS: Considerable work needs to be done to develop audiovisual materials
      and curricula for teaching bedside procedures. Videotape is a valuable medium for
      introducing procedures and ensuring uniformity of technique. After reviewing all
      available videotapes, the author decided that videotapes should be the initial
      part of a multidimensional program for teaching procedures.

PMID- 7515105
TI  - Detection of autoantibodies to neural antigens in the CSF of Japanese
      encephalitis patients and correlation of findings with the outcome.
AB  - This study reports the detection of autoantibodies to myelin basic protein (MBP)
      and neurofilament proteins (NFP) in serum and cerebrospinal fluid (CSF) of
      Japanese encephalitis patients. The diagnosis of Japanese encephalitis was
      confirmed in 72 patients by the presence of virus specific antibodies to JEV in
      the CSF (28/72), viral antigen in the CSF (19/72) and simultaneous presence of
      both antigen and JEV antibodies in the CSF in 25/72 patients. Autoantibodies to
      either purified NFP (10) or MBP (8) or both (17) were detected in the CSF of 35
      patients by ELISA in contrast with the control CSF samples. Amongst them 20 had
      similar antibodies in the serum as well. Correlation of immunological findings
      with the clinical outcome revealed that the presence of autoantibodies in the CSF
      especially to NFP was associated with a fatal outcome (P < 0.05).

PMID- 7515104
TI  - Constitutive CD8 expression allows inefficient maturation of CD4+ helper T cells
      in class II major histocompatibility complex mutant mice.
AB  - Although mature CD4+ T cells bear T cell receptors (TCRs) that recognize class II
      major histocompatibility complex (MHC) and mature CD8+ T cells bear TCRs that
      recognize class I MHC, it is possible that the initial commitment of an immature
      thymocyte to a CD4 or CD8 lineage is made without regard to the specificity of
      the TCR. According to this model, CD4+ cells with class I TCR do not mature
      because the CD8 coreceptor is required for class I MHC recognition and positive
      selection. If this model is correct, constitutive expression of CD8 should allow
      CD4+ T cells with class I-specific TCRs to develop. In this report, we show that
      mature peripheral CD4+ cells are present in class II MHC-deficient mice that
      express a constitutive CD8.1 transgene. These cells share a number of properties
      with the major class II MHC-selected CD4 population, including the ability to
      express CD40 ligand upon activation. Although mature CD4 cells are also
      detectable in the thymus of class II MHC mutant/CD8.1 transgenic mice, they
      represent a small fraction of the mature CD4 cells found in mice that express
      class II MHC. These results indicate that some T cells choose the CD4 helper
      lineage independent of their antigen receptor specificity; however, the
      inefficiency of generating class I-specific CD4 cells leaves open the possibility
      that an instructive signal generated upon MHC recognition may bias lineage
      commitment.

PMID- 7515109
TI  - Inability of interferon-gamma and aminoguanidine to alter Cryptosporidium parvum
      infection in mice with severe combined immunodeficiency.
AB  - Severe combined immunodeficiency (scid) mice have been useful in identifying
      specific host defense systems responsible for containing and eradicating
      Cryptosporidium parvum infection. Adult scid mice were given C. parvum oocysts
      and treated weekly with monoclonal antimurine interferon-gamma (anti-IFN-gamma).
      Anti-IFN-gamma-treated mice had more cryptosporidia seen in the intestines and
      had more severe morphologic changes associated with disease than control mice. To
      assess the mechanism of this effect, infected adult BALB/c and scid mice were
      treated with the nitric oxide synthase inhibitor, aminoguanidine. Infection in
      aminoguanidine-treated mice was not significantly different from that in control
      mice. Next, the effects of pharmacologic doses of IFN-gamma (10,000 IU) on the
      course of cryptosporidiosis in newborn scid mice were evaluated. IFN-gamma did
      not reverse the initial susceptibility of neonatal scid mice to cryptosporidiosis
      and continued treatment with IFN-gamma (10,000 IU weekly) did not alter survival.
      We conclude that IFN-gamma does not exert its anticryptosporidial effect by
      stimulation of nitric oxide production. Deficient IFN-gamma production by
      neonatal lymphocytes does not appear to be responsible for the increased severity
      of infection observed in neonatal animals. Also, IFN-gamma may not be useful in
      treating immunocompromised patients with cryptosporidiosis.

PMID- 7515110
TI  - Arrhythmias.

PMID- 7515108
TI  - Immunohistochemical analysis of extracellular matrix components in synovial
      sarcoma.
AB  - Little attention has been paid to the composition of the extracellular matrix in
      synovial sarcoma, a tumour showing both epithelial and mesenchymal phenotypes. As
      extracellular matrix participates actively in interactions between epithelial and
      mesenchymal tissues, further knowledge of the pathogenesis of this tumour may be
      provided by the study of extracellular matrix components. Therefore, we have
      analysed the immunohistochemical distribution of type I, III, and IV collagen,
      fibronectin, laminin and tenascin in four cases of synovial sarcoma. The pattern
      of immunoreactivity for these molecules varied according to the tissue phenotype
      of the tumour. Mesenchymal tissue labelled mainly for type I and III interstitial
      collagen and fibronectin. The epithelial component was surrounded by a laminin
      and type IV collagen-positive basement membrane, but punctate pericellular
      reactivity for laminin and type IV collagen was also detected among some
      mesenchymal cells. Tenascin was strongly expressed in the mesenchymal tissue
      immediately around epithelial structures and weakly or not at all expressed in
      the monophasic tumours and in mesenchymal tissue distant from epithelial elements
      in the biphasic tumours. These results suggest some resemblances between synovial
      sarcoma and the embryonic development of epithelia from mesenchymal cells,
      providing further support for the concept of an epitheliogenesis from the
      mesenchyme in these tumours.

PMID- 7515111
TI  - The delta subunit of Bacillus subtilis RNA polymerase. An allosteric effector of
      the initiation and core-recycling phases of transcription.
AB  - RNA polymerase purified from Bacillus subtilis contains multiple sigma (sigma)
      factors and an auxiliary subunit known as delta (delta). We have addressed the
      roles of the delta polypeptide in a model transcription cycle using the promoter
      and attenuator of the ilv-leu operon. We demonstrate that delta influences both
      the promoter selection and core recycling phases of the transcription cycle. The
      delta protein functions together with sigma as an initiation subunit of RNA
      polymerase. Remarkably, E sigma delta forms predominantly closed complexes at the
      P(ilv) promoter even at 40 degrees C, whereas E sigma forms open complexes. The
      presence of delta inhibits transcription at low temperatures, presumably because
      delta decreases the rate of open complex formation. In contrast, delta has little
      or no effect on the overall rate of promoter localization and initiation, rate of
      elongation, or termination efficiency. Despite the inhibitory effect of delta on
      DNA-melting, we find that delta stimulates the amount of RNA synthesized from the
      P(ilv) leader region several-fold in multiple cycle reactions due to an increased
      rate of enzyme recycling. These results highlight the importance of delta in
      determining RNA yield during in vitro transcription.

PMID- 7515112
TI  - Gold/Fab immuno electron microscopy localization of troponin H and troponin T in
      Lethocerus flight muscle.
AB  - The position of the large troponin complex relative to myosin crossbridges in
      Lethocerus flight muscle (IFM) has been probed by electron microscopy (EM) using
      monoclonal antibodies against troponin T (TnT) and troponin H (TnH), a heavy
      troponin component found in several insect muscles. Infiltration of gold-tagged
      and plain Fab fragments into glycerinated IFM before fixation established in non
      overlap fibers that the beads every 38.7 nm along thin filaments are troponin.
      Original and optically filtered EM images from 25 nm longitudinal and 15 nm cross
      sections of partially overlapped fibers suggests that epitopes on both TnT and
      TnH are very close to the rear crossbridge of the rigor double chevron. When Fab
      was infiltrated into relaxed fibers and ATP was subsequently removed, the
      resulting rigor crossbridge lattice was disrupted by antibody labeling of the
      troponin. The results confirm that the lattice of rigor crossbridges and troponin
      are congruent and suggest that crossbridges may interact with troponin in IFM,
      possibly serving as a partial basis for the stretch activation characteristic of
      this muscle.

PMID- 7515113
TI  - Crystallization and preliminary X-ray diffraction study of a bacterially produced
      T-cell antigen receptor V alpha domain.
AB  - A recombinant form of the variable domain of the alpha chain of a murine T-cell
      receptor specific for the N-terminal nonapeptide of myelin basin protein in
      association with the major histocompatibility complex class II I-Au molecule has
      been crystallized in a form suitable for X-ray diffraction analysis. This protein
      was secreted into the periplasmic space of Escherichia coli cells and affinity
      purified using a nickel chelate adsorbent. The crystals are orthorhombic, space
      group P2(1)2(1)2, with unit cell dimensions a = 97.7 A, b = 79.6 A, c = 30.4 A
      and diffract to beyond 2.2 A resolution. The ability to crystallize a T-cell
      receptor domain produced in bacteria strongly suggests that the periplasmic space
      can provide a suitable environment for the correct in vivo folding of this class
      of antigen recognition molecules.

PMID- 7515116
TI  - NIAID recommendations for treating HIV infection.

PMID- 7515115
TI  - A meta-analysis of methods to prevent venous thromboembolism following total hip
      replacement.
AB  - OBJECTIVE: While several methods of prophylaxis have been shown to reduce the
      risk of venous thromboembolism following total hip replacement, the safest and
      most effective agent is unclear. To clarify this issue, we performed a meta
      analysis of the randomized trials of methods used to prevent venous
      thromboembolism following total hip replacement. DATA SOURCE: English-language
      human studies articles from 1966 through 1993 were obtained from a MEDLINE
      database search with indexing terms including thromboembolism, hip replacement or
      hip prosthesis, and randomized controlled trials. Additional references were
      obtained from study bibliographies. STUDY SELECTION: The following criteria were
      used to select studies for inclusion: study design--randomized clinical trial;
      study population--patients undergoing elective total hip replacement;
      interventions--aspirin, warfarin, dextran, heparin, low-molecular-weight heparin,
      compression stockings; and outcomes--venous thromboembolism, major hemorrhage.
      DATA EXTRACTION: Methodological and descriptive data from each study were
      abstracted by one author who was blinded to quantitative outcomes data. DATA
      SYNTHESIS: Ninety-one treatment groups and 25 control groups were identified from
      56 trials. Four treatment groups were excluded because of rarely used
      combinations. Trial populations were clinically homogeneous. When compared with
      the control arm, all treatments except aspirin reduced the risk of all deep
      venous thromboses (risk differences range, 0.18 to 0.31; all P values < .05). All
      treatments except aspirin reduced the risk of proximal venous thrombosis (risk
      differences range, 0.09 to 0.18; all P values < .05). Only low-molecular-weight
      heparin and stockings reduced the risk of pulmonary embolism, both with risk
      differences equal to 0.02. The crude risks of clinically important bleeding as
      defined by the individual trials were 0% for stockings, 0.3% for controls, and
      1.8% for low-molecular-weight heparin. CONCLUSIONS: The results suggest that low
      molecular-weight heparin and compression stockings have the greatest relative
      efficacy in preventing venous thromboembolism following total hip replacement.
      Low-molecular-weight heparin may be more effective, though at a small risk of
      clinically important bleeding.

PMID- 7515114
TI  - p53 in prostate cancer: frequent expressed transition mutations.
AB  - BACKGROUND: Carcinoma of the prostate is the second most common cause of cancer
      deaths in men. Little is known about the pathogenesis of this disease and the
      molecular genetic events that contribute to its development. Molecular studies
      have begun to reveal biologic characteristics of this disease, notably, the loss
      of genetic material as determined by studies of restriction fragment length
      polymorphism, oncogene activation, and production and response to growth factors.
      PURPOSE: Our goal was to characterize p53 gene mutations in human carcinoma of
      the prostate and to analyze base-pair changes within the coding regions of p53
      mRNA (exons 4 through 11). METHODS: Forty-four prostate tissue specimens and four
      metastatic lesions were obtained from 48 prostate carcinoma patients who had
      surgical resection. RNA was either immediately extracted or the specimens were
      snap-frozen in liquid N2 and stored at -70 degrees C until used. Total RNA was
      extracted from tumor specimens. Expression of p53 was analyzed by polymerase
      chain reaction (PCR) analysis of mRNA (RNA/PCR). Following confirmation of the
      RNA/PCR products by Southern blotting, quantitation of message levels was
      performed by laser densitometry. Absolute area integrations of the curves
      representing each tissue were then compared after adjustment for the housekeeping
      gene c-N-ras. Two overlapping regions (exons 4-6 and 6-11) were examined by a
      nonisotopic PCR single-strand conformation polymorphism (SSCP) analysis system.
      All specimens displaying SSCP abnormalities were sequenced in both directions to
      confirm the findings. RESULTS: Of the 48 prostate specimens, three (6%) (two
      primary and one metastatic) displayed nearly undetectable expression of p53 mRNA
      (samples PS-70, L113, and PS-95) and 17 (35%) of 48 expressed mutant p53 mRNA
      encoding amino acid substitutions within exons 4-11 (14 of 17) and/or deletions
      within the p53 transcripts (three of 17). Overall, the frequency of p53 gene
      abnormalities that would result in altered protein expression was 20 (42%) of 48
      in the tissue samples from prostate carcinoma patients. Nucleotide base-pair
      transitions of A-->G or T-->C were the most frequent. CONCLUSIONS: p53 mutations
      are common in prostate cancer. The patterns of p53 gene mutations are
      dramatically different from data obtained on other cancers and indicate the
      possible involvement of a carcinogenic agent(s). IMPLICATIONS: Further studies
      are required to determine the biologic role of p53 gene alterations in the
      development and progression of this disease and to determine whether p53
      mutations can be useful as prognostic markers or for the selection of better
      treatments for prostate cancer patients.

PMID- 7515117
TI  - [Anti-thyrotropin (TSH) receptor antibody binding epitopes of TSH receptor: site
      directed mutagenesis approach].
AB  - Anti-TSH receptor antibodies are thought to be involved in the expression of
      autoimmune thyroid diseases, especially Graves' disease and idiopathic myxedema.
      Cloning of TSH receptor gene allowed us to study aspects of its structure and
      function at the molecular level, including autoantibody-binding sites. The long
      extracellular domain of TSH receptor was presumed to contain antibody-binding
      site. Site-directed mutagenesis of this domain defined regions important for
      autoantibodies. The C-terminal region of the extracellular domain, residues 295
      306, 387-395 and tyrosine 385 were determinants of the "blocking-type" antibody,
      which were present in patients with primary hypothyroidism. And the N-terminal
      region, residues 34-37, 40, 42-45 and 52-56 were the site of the "stimulatory
      type" antibody interactions, important in patients with Graves' disease.

PMID- 7515118
TI  - [Analysis of epitopes for TSH receptor autoantibodies using TSH receptor/LH-CG
      receptor chimeras].
AB  - Graves' disease and idiopathic myxedema are autoimmune thyroid diseases and are
      caused by thyrotropin (TSH) receptor autoantibodies, thyroid stimulating antibody
      (TSAb) in Graves' disease and thyroid stimulation blocking antibody (TSBAb) in
      idiopathic myxedema. Studies with TSH receptor/lutropin-chorionic gonadotropin
      (LH-CG) receptor chimeras show that binding sites or epitopes on human TSH
      receptor for TSH, TSAb and TSBAb are different and, moreover, epitopes for TSAb
      are heterogeneous in different Graves' patients. Epitopes for TSAb exist in the N
      terminal region and those for TSBAb in the C-terminal region on human TSH
      receptor extracellular domain.

PMID- 7515119
TI  - [On the localization of the binding site(s) of antibodies against TSH receptor
      using synthetic peptides].
AB  - In order to elucidate autoimmune B-cell recognition sites of human thyrotropin
      receptor (TSHR), nine overlapping synthetic peptides (residues 12-30, 24-44, 151
      175, 171-195, 308-328, 324-344, 339-364, 359-380, and 375-399) were synthesized
      and biological activities of antibodies against each of the peptide were
      examined. It was shown that antibodies against TSHR 12-30, 24-44, 151-175, 171
      195, 324-344, and 359-380 had thyroid stimulating antibody activity (TSAb),
      whereas antibodies against 339-364, 359-380, and 375-399 had thyroid stimulation
      blocking activity (TSBAb). From these results it was concluded that epitopes
      where TSH receptor antibodies with TSAb and TSBAb activities are bound are widely
      located in N-terminal, mid portion, and C-terminal regions.

PMID- 7515120
TI  - [Thyroid stimulating activity of human TSH-R peptide antibody].
AB  - We have synthesized a TSH-R peptide (N-peptide) corresponding to the unique N
      terminal segment (#29-57) and immunized it into rabbits. We found that the N
      peptide antibody possessed thyroid stimulating antibody (TSAb) activity but
      lacked TSH-binding inhibitor immunoglobulin (TBII) activity. We then produced
      rabbit antibodies against the peptides corresponding to the mid-region (#172-202,
      C-peptide), the region near the transmembrane domain (#341-370, P-peptide), and
      the extracellular loops (#648-662, E1-peptide; #561-580, E2-peptide; #648-662, E3
      peptide). All these peptide-antibodies showed also TSAb activities. These results
      suggest that the domains responsible for TSAb might span the entire extracellular
      components of the receptor and that even the extracellular loops are the
      candidates for the epitope against autoantibodies from Graves' patients.

PMID- 7515121
TI  - [Identification and immunopathogenicity of a common T cell epitope between human
      thyroglobulin and human thyroid peroxidase].
AB  - Human thyroglobulin (hTg) and human thyroid peroxidase (hTPO) share common B cell
      epitopes recognized by autoantibodies in patients with chronic autoimmune
      thyroiditis. Furthermore, we have demonstrated a functional common T cell epitope
      between hTg and hTPO in mice. Four hTg peptides in which 5 amino acid residues
      were identical to those of hTPO, and one hTPO peptide were prepared. Among these
      peptides, Tg-P4 (residues 2730-2743) and TPO-P4 (residues 118-131) shared the
      common T cell epitope and both peptides were highly antigenic. In addition, when
      the spleen cells from mice immunized with mouse Tg (mTg) were restimulated in
      vitro by Tg-P4 or TPO-P4, as well as by mTg, these cells transferred thyroiditis
      to naive recipient mice. These findings indicate that this common T cell epitope
      is immunogenic and related to the development of murine experimental autoimmune
      thyroiditis. The common T cell epitope between hTg and hTPO may play a role in
      the pathogenesis of human autoimmune thyroid disease.

PMID- 7515122
TI  - [A case of gastric cancer with liver metastasis showing positive
      immunohistochemical staining of PIVKA-II on the stomach and liver].

PMID- 7515123
TI  - [A study of biological characteristics of large bowel adenocarcinomas showing
      mucin production; examination of histological differentiation and cell kinetics].
AB  - In order to clarify the biological behavior of mucin producing cancers of colon,
      we analyzed 32 cases showing histological heterogeneity in the tumors, by mucin
      histochemistry. 28 cases were mucinous adenocarcinoma, forming with tubular
      structures, and the remaining 4 cases were signet-ring cell carcinomas. HID-AB
      stain demonstrated that the mucin component was almost similar to that of normal
      mucosa around the cancer. In the tubular forming portions, in which polyploid or
      aneuploid cells were often detected, the growth fraction of cancers was
      significantly higher than in that of the other portions.

PMID- 7515124
TI  - [Side effects of interferon on endocrine and respiratory system in 545 cases of
      chronic hepatitis C].
AB  - We investigated the side effects of interferon (IFN) on the endocrine and
      respiratory system in 545 cases of chronic hepatitis C. Eleven of 494 (2.2%)
      patients with chronic hepatitis C who were treated with natural or recombinant
      interferon (IFN) developed thyroid disease while on treatment. Eight patients
      developed hyperthyroidism and 3 patients developed hypothyroidism. All 11
      patients required definitive therapy, who became euthyroid after the therapy. Two
      patients received nIFN alpha and one patient received rIFN alpha 2b developed
      diabetes mellitus. Two patients received rIFN alpha 2a and rIFN alpha 2b,
      respectively, developed interstitial pneumonia 12 weeks and 24 weeks later,
      respectively. One patient showed positive reaction for RA test and LE factor and
      positive LE cell, and complained of fever, arthralgia and dry cough. These
      phenomenon disappeared after the cessation of IFN therapy.

PMID- 7515125
TI  - [The early lesions of renal amyloidosis].
AB  - Two patients with minimal amyloid deposition in association with nephrotic
      syndrome are reported. Since the amyloid deposits in each renal biopsy specimen
      were inconspicuous, both were first thought to be minimal glomerular changes. A
      few widely scattered, silver-positive, epimembranous spicules were found on
      careful reexamination by light microscopy. Congo red stain and electron
      microscopy confirmed the presence of small glomerular amyloid deposits and
      amyloid fibrils. Furthermore, immuno-fluorescence microscopy showed partial IgA
      deposits in the mesangial area and capillary wall. We therefore urge careful
      examination to detect amyloid deposits of all kidney biopsy specimens of minor
      glomerular abnormalities, or glomerulonephritis with IgA deposits from elderly
      patients with nephrotic syndrome. Light microscopy of Congo-red-stained sections
      and electron microscopy of the fibrillar structure very useful for the detection
      of small amyloid deposits.

PMID- 7515126
TI  - [Palliative surgery of congenital heart disease in early infancy].
AB  - A total of 38 patients aged under 3 months with congenital heart disease (CHD)
      underwent palliative surgery between April, 1988 and March, 1993. The mean age at
      operation was 28.0 (range 1 to 87) days. Palliative procedures were: pulmonary
      artery banding (PAB) in 14 patients (IAA complex: 4, CoA complex: 6, AVSD: 2, TA:
      2), Blalock-Taussig shunt (BTS) in 12 (TOF: 2, TGA: 1, AVSD: 1, PA-IVS: 3, PA
      VSD: 3, PA-SV: 1, PA-AVSD: 1), Brock operation in 6 (PPS: 2, PA-IVS: 3, PA-SV:
      1), Blalock-Hanlon operation (BH) with PAB in 2 (MA-SV: 2) and Norwood operation
      (NRD) in 4 (HLHS: 4). PAB of IAA or CoA complex was performed just after the
      repair of IAA or CoA. Overall operative mortality was 23% (PAB: 14.3, BTS: 8.3,
      Brock: 33.3, NRD: 100%). One week after PAB, pulmonary artery pressure (PAP)
      decreased significantly compared to the intraoperative PAP value after PAB (43.1
      +/- 16.2, 32.3 +/- 9.0 mmHg, p < 0.05, respectively). Pulmonary artery index
      (PAI), which is an index of pulmonary artery growth, after BTS increased
      significantly compared to the preoperative value (mean follow-up interval: 22.1
      months) (379.5 +/- 101.4, 159.3 +/- 51.2, p < 0.001, respectively). During Brock
      operation, balloon catheter was used in order to dilate pulmonary valve. One year
      after Brock operation, mean pressure gradient through the pulmonary valve 22.6
      mmHg. Two-staged corrections of CHD will be performed both safely and
      successfully by effective palliations at the first stages in early infancy.

PMID- 7515127
TI  - [Clinical experiences of granulocyte colony stimulating factor for
      granulocytopenia after AC bypass].
AB  - We have successfully treated 3 cases of granulocytopenia, using Granulocyte
      Colony Stimulating Factor (G-CSF) after AC bypass surgery. All cases were male,
      aged 68, 75 & 54 years old, and underwent AC bypass surgery without transfusion
      except in case 1. Granulocyte cell counts decreased to 135/mm3 on 39th post
      operative days (POD) in case 1, 624/mm3 on 13 rd POD in case 2, and 514/mm3 on
      20th POD in case 3. In case 1, 300 micrograms of G-CSF was given intravenously
      for 3 days. In case 2, 100 micrograms of G-CSF for 1 day and 50 micrograms for 3
      days was given subcutaneously, and in case 3, 100 micrograms of G-CSF was also
      given subcutaneously for 2 days. And their granulocyte cell counts all increased
      within few days. G-CSF is effective for patients with granulocytopenia after AC
      bypass surgery, but we need more experiences to know the best way of
      administration.

PMID- 7515128
TI  - Classical and channel-like urate transporters in rabbit renal brush border
      membranes.
AB  - The precise mechanism by which urate is transported across rabbit renal proximal
      tubule luminal membranes has not been defined. To determine whether urate flux
      across this membrane represents simple diffusion or transport on specific
      carriers, urate uptake was examined in brush border membrane vesicles that were
      prepared by a Mg+(+)-aggregation technique and then exposed to CuCl2. Na(+)
      independent, voltage sensitive urate transport was demonstrated in these Cu+(+)
      exposed vesicles. Transport was trans-stimulated by urate and cis inhibited by
      pyrazinoic acid and oxonate. A small fraction of transported urate and urate in
      the extravesicular fluid was oxidized to allantoin. Kinetic analysis revealed the
      presence of two kinetically distinct transporters; a channel-like carrier that
      was inhibited by pyrazinoic acid and oxonate, and a high-affinity, classical,
      saturable carrier that was inhibited by higher concentrations of oxonate. These
      studies provide the first direct evidence for carrier-mediated urate transport in
      rabbit renal brush-border membranes and demonstrate that the rabbit
      transporter(s) share a number of properties with the urate uniporter in rat
      proximal tubule cell membranes.

PMID- 7515131
TI  - Safety belt education using visual crash images and low-cost incentives.
AB  - Automobile safety belt use among teen-agers remains low despite high crash
      morbidity and mortality. This article describes a model of a community-based
      safety belt promotional program. Ten public high schools, with student club and
      administrative support, were selected from across Mississippi. Safety belt
      assemblies, which created vivid crash images, were conducted using police
      officers, ambulance personnel, people with paraplegia, football players, and
      others. Low-cost incentives were awarded to buckled students over a 10-week
      period. Implementation of the program resulted in a mean increase of 21% in male
      safety belt use and 17% in female safety belt use. Concepts used in the program
      are reproducible, at minimal cost, by using personnel found in most communities.

PMID- 7515129
TI  - Effects of guanidino and uremic compounds on nitric oxide pathways.
AB  - Aminoguanidine, NG-monomethyl-L-arginine (L-NMMA), NGNGdimethyl-L-arginine
      (asymmetric dimethylarginine; ADMA), creatinine, guanidinosuccinic acid,
      guanidinoproprionic acid and methylguanidine were added to cultures of activated
      murine macrophages. Only aminoguanidine, ADMA, L-NMMA and methylguanidine
      inhibited nitrite production in a dose-dependent manner. In the presence of 100
      microM arginine, nitrite production was inhibited by 31.8 +/- 7.1% by ADMA (100
      microM; P < 0.01) but the same dose of methylguanidine was without effect. A
      higher dose of methylguanidine (1000 microM) inhibited nitrite production by 47.6
      +/- 5.6% (P < 0.001). The effects of these compounds were also tested on
      relaxation of human saphenous veins. L-NMMA and ADMA inhibited endothelium
      dependent relaxations (EC50 = 4.7 +/- 1.1 microM and 17.9 +/- 4.9 microM,
      respectively); methylguanidine caused endothelium-independent contractions and
      reversed the relaxations to bradykinin and sodium nitroprusside (EC50 > 100
      microM); aminoguanidine was without effect. The results of this study suggest
      that of the guanidino compounds which accumulate in renal failure, only ADMA is a
      potent inhibitor of nitric oxide (NO) synthesis. Methylguanidine is a weak
      inhibitor of nitric oxide synthesis, whereas the closely related compound
      aminoguanidine appears to inhibit selectively the inducible isoform of nitric
      oxide synthase and has no effect on constitutive NO synthase in human veins.

PMID- 7515132
TI  - Experimental use of a modified fibrin glue to induce site-directed angiogenesis
      from the aorta to the heart.
AB  - From 10 cultures of manipulated Escherichia coli bacteria expressing the class I
      heparin-binding growth factor polypeptide alpha-endothelial cell growth factor,
      11.2 +/- 0.7 mg alpha-endothelial cell growth factor was eluted by heparin
      sepharose affinity chromatography. Analysis of molecular weight (17,000 kD) was
      done by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      purification of the growth factor was done by high-performance liquid
      chromatography. The harvested alpha-endothelial cell growth factor was proved by
      protein blotting. To assess the growth-promoting activity, we did an endothelial
      cell growth assay by comparing adult human endothelial cell control cultures,
      without adding growth factor to the culture medium, with adult human endothelial
      cell cultures with 0.02 to 20.0 ng/ml alpha-endothelial cell growth factor and
      1.0 ng/ml heparin and with adult human endothelial cell cultures with alpha
      endothelial cell growth factor but without heparin. Tritiated thymidine counts
      proved the significant growth-promoting activity of alpha-endothelial cell growth
      factor. In 10 experimental animals modified fibrin glue containing 1 microgram
      alpha-endothelial cell growth factor was implanted between the aorta and the
      myocardium of the left ventricle and results were compared with those in five
      control animals that received normal fibrin glue without growth factor. After 9
      weeks of implantation, angiography and histologic investigation showed newly
      grown vascular structures between the aorta and the myocardium in all
      experimental animals, but none in the control animals. Our study proved the
      feasibility of initiating site-directed formation of new blood vessel structures
      to the heart by a modified fibrin glue implant containing angiogenic growth
      factor alpha-endothelial cell growth factor.

PMID- 7515130
TI  - Mitochondrial schwannopathy and peripheral myelinopathy in a rabbit model of
      dideoxycytidine neurotoxicity.
AB  - BACKGROUND: The reverse transcriptase inhibitor, 2',3'-dideoxycytidine (ddC),
      causes a dose-limiting peripheral neuropathy in humans, the mechanism of which is
      unknown. Rabbits given ddC develop peripheral myelinopathy and axonopathy, but it
      has not been determined if either the myelin or axonal changes are primary or if
      they occur concurrently. EXPERIMENTAL DESIGN: To characterize sequential
      development of the ddC-induced neuropathy, 40 rabbits were given either vehicle
      or ddC by oral intubation at a dose of 35 mg/kg per day for 24 weeks.
      Electrophysiologic studies, pathologic examination of peripheral and central
      nervous system and skeletal muscle, and biochemical analysis of the sciatic nerve
      were performed at baseline (electrophysiology only) and after 8, 12, 16, 20, and
      24 weeks of treatment. RESULTS: Neuropathologic changes in peripheral nerves were
      first evident at 16 weeks and were more pronounced at 20 and 24 weeks; onset of
      paresis occurred at week 20, whereas clear electrophysiologic deficits were seen
      only at week 24. Electrophysiologic changes were prolonged F-waves (measure of
      proximal motor conduction) and minor changes in distal conduction measurements.
      Pathologic changes included myelin splitting, intramyelinic edema, demyelination,
      and remyelination of the largest diameter nerve fibers in the ventral root and
      sciatic nerve. Axonal degeneration and reduction in axonal diameter were seen.
      Enlarged mitochondria with abnormal ultrastructure were present in Schwann cells
      of those animals with a myelinopathy. Mitochondrial abnormalities or other signs
      of degeneration were not seen in neurons of the dorsal root ganglia or in
      skeletal muscle. Significant changes were not present in myelin protein
      composition, myelin lipid composition, or activity of the myelin-specific enzyme
      2',3'-cyclic nucleotide 3'-phosphohydrolase. Major reductions in levels of
      protein zero (P0, the homophilic adhesion protein of myelin) were not seen;
      however, the turnover rate of P0 was reduced as P0 messenger RNA expression in
      ddC-treated sciatic nerves decreased to 30 to 50% of control values. CONCLUSIONS:
      The peripheral neuropathy caused by ddC in rabbits is characterized as a
      myelinopathy of the proximal portion of the nerve fibers and as an axonopathy
      involving both proximal and distal fibers. The myelinopathy was associated with
      enlarged and abnormally shaped mitochondria in Schwann cells and is consistent
      with an effect of ddC on structure and function of Schwann cell mitochondria.
      Altered Schwann cell metabolism was evident by reduced levels of P0 messenger
      RNA, loss of homophilic myelin adhesion at the intraperiod line, and subsequent
      intramyelinic edema. Because axonal degeneration occurred concurrently with the
      myelin changes, it could not be determined if axonal changes were secondary to
      serve myelinic edema or if they represented a primary effect of ddC on neurons.

PMID- 7515134
TI  - Factors influencing the natural history of colorectal liver metastases.
AB  - Palliative treatment of unresectable colorectal liver metastases is common and
      often justified with reference to historical data on the natural history of the
      disease. However, in view of the improved diagnostic accuracy of modern imaging
      techniques, these previously published series do not provide sufficient guidance
      to judge the prognostic efficacy of palliative treatment. In the late 1970s we
      started prospectively to collect data on consecutive patients with colorectal
      liver metastases according to a standard protocol. We now present data derived
      from this series on factors that may affect outcome in untreated patients.
      Between January, 1980, and December, 1990, 1099 consecutive patients were
      recorded, of whom 566 (51.5%) received no treatment for their hepatic tumour.
      Excluding 34 early deaths and 48 patients with a second malignant tumour, 484
      patients provided the basis for analysis. All patients were followed up to July
      1, 1993, or death. At the closing date of the study only 1 untreated patient was
      still alive. The impact of various factors on survival was analysed by univariate
      and multivariate analyses. Six independent determinants of survival were
      identified in the following order: percentage liver volume replaced by tumour
      (LVRT), grade of malignancy of the primary tumour, presence of extrahepatic
      disease, mesenteric lymph-node involvement, serum carcino-embryonic antigen, and
      age. The subsequent combination of the independently significant factors,
      separately for patients with up to or more than 25% LVRT, yielded a prognostic
      tree that displayed median survival times of various subgroups of 3.8 to 21.3
      months. These findings provide a framework to estimate the survival expectancy of
      untreated patients, thereby allowing improved assessment of the prognostic
      significance of palliative therapeutic approaches.

PMID- 7515135
TI  - The very last minute slide.

PMID- 7515133
TI  - Screening anti-HIV Chinese materia medica with HIV and equine infectious anemic
      virus reverse transcriptase.
AB  - The inhibitory activities of human immunodeficiency virus reverse transcriptase
      (HIV-RT) inhibitors PFA and Suramin against HIV-RT and equine infectious anemic
      virus reverse transcriptase (EIAV-RT) were studied in this paper. The 50%
      inhibitory concentration (IC50) of HIV-RT and EIAV-RT treated by PFA and Suramin
      were 0.2 mumol, 9.8 mumol and 17 mumol, 19.9 mumol, respectively. More than
      thirty Chinese medicines, including recipes, herbs, extracts of traditional
      materia medica and isolated compounds were tested using HIV-RT and EIAV-RT as
      target enzymes. It was found that 5 crude extracts such as Rhizoma Polygoni
      Cuspidati, and Radix Notoginseng, 7 isolated compounds like Flavone of Ramulus
      Visci, Flavone of Ajuga Decumbens Thumb, and Aristolochic acid, as well as the
      extract of the complex prescription Xiao Chai Hu Tang have shown various
      inhibitory actions on these two enzymes. The activities of the two enzymes were
      comparable, but HIV-RT was more sensitive, suggesting that HIV-RT can be used as
      index for the screening of anti-aids drugs.

PMID- 7515137
TI  - Screening for prostate cancer.

PMID- 7515138
TI  - Screening for prostate cancer.

PMID- 7515136
TI  - Screening for prostate cancer.

PMID- 7515140
TI  - Alpha 1-adrenoceptors in human prostate: characterization and binding
      characteristics of alpha 1-antagonists.
AB  - The role of alpha 1-adrenoceptors in the mediation of autonomic functions,
      particularly in the control of the cardiovascular system, is widely known. It has
      been shown that alpha 1-adrenoceptors localized in human prostate mediate the
      contraction of prostatic smooth muscles which produces an increase in the
      intraurethral pressure and thus, these receptors are important in the regulation
      of bladder outlet resistance. Alpha 1-antagonists such as prazosin relieve the
      symptoms of bladder outlet obstruction in men with symptomatic benign prostatic
      hypertrophy (BPH) by blocking alpha 1-adrenoceptors, thereby decreasing prostatic
      tone and urethral resistance. Thus, alpha 1-adrenergic stimulation may be one of
      the most important factors in the development of urinary obstruction in BPH.
      Alpha 1-adrenoceptors in human prostate have been identified and characterized
      extensively by functional, radioligand binding and molecular biological
      techniques. These studies provide evidence in support of the concept that the
      alpha 1C-subtype forms the majority of alpha 1-adrenoceptors in human prostatic
      smooth muscles. It has been shown that YM617 (tamsulosin) and naftopidil have
      higher affinities to alpha 1-adrenoceptors in the prostate than in the aorta.
      Some alpha 1-antagonists, such as prazosin and terazosin, are not selective with
      respect to alpha 1-adrenoceptor subtypes, while others, such as 5-methylurapidil
      and indoramin, show higher potencies for alpha 1C-adrenoceptors and much lower
      potencies for alpha 1A- and alpha 1B-subtypes. In conclusion, the recent findings
      from pharmacological and molecular biological studies indicate that selective
      antagonists of alpha 1C-adrenoceptors could be effective in the treatment of
      urinary obstruction in symptomatic BPH with fewer cardiovascular side effects.

PMID- 7515139
TI  - A four-drug pain regimen for head and neck cancers.
AB  - Twenty patients with end-stage head and neck cancer, unresponsive to either
      acetaminophen with codeine or oxycodone hydrochloride, were placed on a four-drug
      analgesic regimen consisting of methadone hydrochloride, Trilisate or
      acetaminophen, a tricyclic antidepressant, and, in most cases, hydroxyzine. All
      drugs could be delivered through a feeding tube, making this regimen appropriate
      for dysphagic patients. The efficacy of this nonparenteral regimen was assessed
      by structured pretreatment and posttreatment interviews that addressed pain
      intensity, activity, and sleep levels. All of the patients showed improvement in
      their pain levels and 16 of the 20 had a > or = 50% improvement in all of their
      pain ratings (P < .01) that persisted until death (2 to 10 months later).
      Excellent results and ease of administration make this regimen a good choice for
      analgesia in terminal patients.

PMID- 7515141
TI  - Hepatitis C virus markers in patients with long-term biochemical and histological
      remission of chronic hepatitis.
AB  - We measured hepatitis C virus (HCV) RNA and antibodies against HCV recombinant
      proteins (C22/S1, E1/S2, E2/NS1, C33/NS3, C100/NS4, NS5) in serial serum samples
      from 22 interferon-treated patients with a long-term follow up (range: 36-44
      months). Eleven of them showed persistently normal liver function tests and a
      significant histological amelioration or a complete resolution of chronic
      hepatitis (long-term responders, LTRs). In the remaining 11 patients (non
      responders (NRs)) liver function tests normalized temporarily during therapy or
      remained unchanged. At the end of the follow up (3 years), viraemia was
      undetectable in six of 11 LTRs (54.6%). HCV-RNA was always detectable in the
      serum of NRs (p = 0.017). At admission, anti-C22/S1, anti-E1/S2, anti-E2/NS1,
      anti-C33/NS3, anti-C100/NS4 and anti-NS5 were detected in 95.4%, 40.9%, 77.3%,
      95.4%, 72.7% and 77.3% of the patients, respectively. Three years after
      suspension of therapy, anti-C100/NS4 was undetectable in five of six (83.3%) LTRs
      who cleared HCV-RNA and in only one with ongoing viraemia (20%). Anti-E2/NS1 was
      undetectable in 54.5% of LTRs and in no NRs (p = 0.067). Anti-E1/S2 was detected
      more frequently in LTRs than in NRs (81.8% vs 45.5%). Serum levels of anti
      C22/S1, C33/NS3 and NS5 did not change during therapy and the follow up in either
      group of patients. The clearance of viraemia in LTRs was associated with that of
      anti-C100/NS4 (p = 0.017). Serum HCV-RNA and anti-C100/NS4 appear suitable tools
      for monitoring patients who respond to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515143
TI  - [Prevalence of anti-hepatitis C antibody carriers in a military population
      engaged in overseas missions].

PMID- 7515142
TI  - Hepatitis B and C virus infection as risk factors for liver cirrhosis and
      cirrhotic hepatocellular carcinoma: a case-control study.
AB  - To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infection are risk factors for liver cirrhosis and hepatocellular carcinoma
      (HCC), a case-control study of 102 cirrhotic HCC patients, 102 sex-matched and
      age-matched patients with liver cirrhosis, and 102 matched patients with non
      hepatic disease controls was performed. The prevalences of hepatitis B surface
      antigen (HBsAg) and antibody to HCV (anti-HCV) in HCC (70.5%, 39.2%) and liver
      cirrhosis (74.5%, 27.4%) were higher than controls (16.6%, 10.5%) (P = 0.0001).
      In HBsAg-negative patients, the prevalence of anti-HCV in cirrhotic HCC (66.6%)
      and liver cirrhosis (46.1%) was higher than in controls (10.5%; P = 0.0001).
      There was no such difference in HBsAg-positive patients. Multivariate analysis
      revealed that both HBsAg and anti-HCV were important risk factors for HCC (odds
      ratio, 6.52 and 4.59, respectively) and liver cirrhosis (odds ratio, 4.22 and
      2.29, respectively). There was no difference in odds ratio when HCC and liver
      cirrhosis were compared. Our result implies that both HBV and HCV are independent
      risk factors for cirrhotic HCC and liver cirrhosis in Taiwan.

PMID- 7515146
TI  - Aprotinin to decrease bleeding in cardiac surgery.

PMID- 7515144
TI  - mRNAs in the methanogenic archaeon Methanococcus vannielii: numbers, half-lives
      and processing.
AB  - Cells from the early exponential growth phase of cultures of the methanogenic
      archaeon Methanococcus vannielii have been shown to contain c. 180 transcripts of
      the mcrBDCGA (mcr) operon, c. 100 transcripts of the MvaL1,L10,L12 (Mva) operon,
      c. 8 transcripts of the argG gene and c. 1 transcript of the secY gene. These
      values decreased to c. 50 mcr transcripts, c. 30 Mva transcripts, c. 3 argG
      transcripts and < 1 secY transcript per cell as the cultures entered the
      stationary phase of growth. Addition of bromo-ethanesulphonate (BES) or removal
      of H2 inhibited growth and RNA synthesis in vivo and, at 37 degrees C in the
      presence of BES, the half-lives of the mcr, Mva, argG and secY transcripts were
      found to be 15 min, 30 min, 57 min and 7 min, respectively. Addition of
      puromycin, pseudomonic acid or virginiamycin also inhibited growth but did not
      inhibit transcription. In the presence of puromycin the half-lives of the mcr and
      Mva transcripts increased c. 4.6-fold and c. 3.5-fold, respectively, and there
      was a net accumulation of the Mva transcript. Addition of pseudomonic acid or
      virginiamycin also increased the half-life of the Mva transcript and also
      resulted in the accumulation of a second, shorter Mva transcript but did not
      increase the half-life of the mcr transcript. Transcription of the mcr operon was
      not stimulated by partial inhibition of methanogenesis.

PMID- 7515145
TI  - A disturbance of interferon synthesis with the hyperproduction of unusual kinds
      of interferon can trigger autoimmune disease and play a pathogenetic role in
      AIDS: the removal of these interferons can be therapeutic.
AB  - Disturbances of interferon synthesis with the hyperproduction of unusual kinds of
      interferons may be the initial step which triggers autoimmune disease through a
      chain of pathological reactions including the disturbances of several
      immunological and cytokine cascades. Prolonged circulation of this interferon may
      be a predictive marker of an autoimmune condition; the administration of
      interferons to animals or humans with autoimmune disease or an underlying or
      latent autoimmune condition can exacerbate or trigger the disease. Healthy people
      do not have interferon in their blood. This fundamental disturbance of interferon
      synthesis can result either from a genetic predisposition or from the influence
      of certain viruses (or viral particles) or both factors together. AIDS has many
      features similar to autoimmune disease, including the hyperproduction of aberrant
      interferon, a type with restricted anti-HIV activity, protectively induced by HIV
      to allow its continued replication and survival. This interferon stimulates the
      production of certain cytokines and autoantibodies which help unleash the
      potentially self-destructive powers of the immune system, bringing immunological
      chaos. In other words, while usual viruses induce normal interferon, which
      protects the cells against viral infection, HIV induces an abnormal, defective
      kind of interferon which ensures virus survival. Since there is no known
      effective method of destroying HIV directly, removing links in this chain of
      reactions could indirectly destroy HIV and possibly help restore immune
      functioning.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515147
TI  - ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal
      growth factor.
AB  - Conflicting results concerning the ability of the epidermal growth factor (EGF)
      receptor to associate with and/or activate phosphatidylinositol (PtdIns) 3-kinase
      have been published. Despite the ability of EGF to stimulate the production of
      PtdIns 3-kinase products and to cause the appearance of PtdIns 3-kinase activity
      in antiphosphotyrosine immunoprecipitates in several cell lines, we did not
      detect EGF-stimulated PtdIns 3-kinase activity in anti-EGF receptor
      immunoprecipitates. This result is consistent with the lack of a phosphorylated
      Tyr-X-X-Met motif, the p85 Src homology 2 (SH2) domain recognition sequence, in
      this receptor sequence. The EGF receptor homolog, ErbB2 protein, also lacks this
      motif. However, the ErbB3 protein has seven repeats of the Tyr-X-X-Met motif in
      the carboxy-terminal unique domain. Here we show that in A431 cells, which
      express both the EGF receptor and ErbB3, PtdIns 3-kinase coprecipitates with the
      ErbB3 protein (p180erbB3) in response to EGF. p180erbB3 is also shown to be
      tyrosine phosphorylated in response to EGF. In contrast, a different mechanism
      for the activation of PtdIns 3-kinase in response to EGF occurs in certain cells
      (PC12 and A549 cells). Thus, we show for the first time that ErbB3 can mediate
      EGF responses in cells expressing both ErbB3 and the EGF receptor.

PMID- 7515151
TI  - Variable domain-identical antibodies exhibit IgG subclass-related differences in
      affinity and kinetic constants as determined by surface plasmon resonance.
AB  - We have analysed the binding of variable domain-identical mouse monoclonal
      antibodies (mAb) of the IgG3, IgG1 and IgG2b subclasses, as well as F(ab')2
      fragments derived from the IgG3 and IgG1 mAb, to a multivalent glycoprotein
      target. Using a biosensor device (BIAcore, Pharmacia Biosensor) that measures the
      mass of the antibody (or other receptor molecule) deposited on a sensor chip
      displaying the relevant epitopes, we found that the IgG3 mAb binds more
      effectively than the other antibody species at a high but not a low epitope
      density. The greater functional affinity associated with the IgG3 mAb, at high
      epitope density, was correlated with both slower dissociation rate constants and
      faster association rate constants in comparison with the IgG1 and IgG2b mAb and
      the F(ab')2 fragments derived from the IgG3 and IgG1 mAb. Evidence for slower
      dissociation kinetics for the IgG3 mAb versus the IgG1 and IgG2b mAb was also
      obtained by ELISA and flow cytometry. These results demonstrate that: (1)
      differences in heavy chain constant (CH) domains can significantly influence
      apparent functional affinity for multivalent antigen, as determined without the
      use of covalently modified primary or secondary antibodies; (2) differences in CH
      domains can alter both association and dissociation rate constants for
      interactions between IgG antibodies and multivalent antigen; and (3) these
      effects of CH domains depend on epitope density. The effect of constant region
      differences on the apparent association rate constants suggests new approaches
      for achieving better binding or functional effectiveness through antibody
      engineering.

PMID- 7515152
TI  - Structural characteristics of four human hybridoma antibodies specific for the
      pp65 protein of the human cytomegalovirus and their relationship to human
      rheumatoid factors.
AB  - Four human hybridoma antibodies directed against the human cytomegalovirus (CMV)
      were characterized with respect to their immunoglobulin gene usage and expression
      of rheumatoid factor (RF) associated idiotypes and variable region epitopes. The
      aims of these experiments were: (1) to characterize the immunoglobulin gene usage
      of four antibodies directed against a single protein of a human pathogen; and (2)
      to examine how this humoral response may be linked to the production of RFs,
      autoantibodies found in the majority of patients with rheumatoid arthritis (RA).
      All four anti-CMV antibodies were of the gamma heavy chain isotype and were
      specific for the immunodominant 65 kDa viral matrix phosphoprotein (pp65). The
      four anti-pp65 antibodies expressed different light (L) and heavy (H) chain
      variable region gene combinations. These were: VkIII/VH3, V lambda 1/VH3, V
      lambda 1/VH4 and V lambda 3/VH3, respectively for the HCV-2, HCV-3, HCV-63 and
      HCV-65 hybridoma cell lines. Although none had RF activity, each of these
      antibodies expressed a unique set of RF-associated determinants, implying
      different three-dimensional configurations of the variable regions of these
      antibodies. The HCV-2 antibody, however, had the most extensive similarities to
      human RFs since it not only expressed the greatest number of RF-associated
      determinants but also had a protein sequence that was very homologous to RFs of
      the "Po" idiotypic family. Furthermore, predicted germline gene usage by anti-CMV
      antibodies and RFs suggest that some are encoded by identical or similar genes
      and that the different specificities are achieved by somatic mutations in the L
      and H chain complementarity determining regions (CDRs) and genetic diversity in
      the H chain CDR3.

PMID- 7515149
TI  - Tissue-specific expression of the human CD19 gene in transgenic mice inhibits
      antigen-independent B-lymphocyte development.
AB  - CD19 is a B-cell-specific member of the immunoglobulin superfamily expressed from
      early pre-B-cell development until plasma cell differentiation. In vitro studies
      demonstrate that the CD19 signal transduction molecule can serve as a
      costimulatory molecule for activation through other B-lymphocyte cell surface
      molecules. However, much remains to be known regarding how CD19 functions in vivo
      and whether CD19 has different roles at particular stages of B-cell
      differentiation. Therefore, transgenic mice overexpressing the human CD19 (hCD19)
      gene were generated to determine whether this transgene would be expressed in a B
      lineage-specific fashion and to dissect the in vivo role of CD19 in B-cell
      development and activation. Expression of the human transgene product was
      specifically restricted to all B-lineage cells and appeared early in development
      as occurs with hCD19. In addition, expression of hCD19 severely impaired the
      development of immature B cells in the bone marrow, with dramatically fewer B
      cells found in the spleen, peripheral circulation, and peritoneal cavity. The
      level of hCD19 expressed on the cell surface correlated directly with the
      severity of the defect in different transgenic lines. These results demonstrate
      that the hCD19 gene is expressed in a lineage-specific fashion in mice,
      indicating that the hCD19 gene may be useful for mediating B-lineage-specific
      expression of other transgene products. In addition, these results indicate an
      important role for the lineage-specific CD19 molecule during early B-cell
      development before antigen-dependent activation.

PMID- 7515150
TI  - Myogenic differentiation triggered by antisense acidic fibroblast growth factor
      RNA.
AB  - Acidic fibroblast growth factor (FGF) and related family members regulate
      differentiation in organisms as diverse as Xenopus laevis and mammals. We
      utilized a well-characterized model of myogenic development to directly assess
      the importance of endogenously produced FGF in controlling differentiation. A
      role for endogenous FGF is suggested by the previous finding that acidic and
      basic FGF abundance in cultured myocytes decreases during differentiation. In
      this study we inhibited the endogenous production of FGF in murine Sol 8
      myoblasts by using antisense RNA and observed precocious myogenic
      differentiation. Exogenously supplied acidic FGF rescues this phenotype. Further
      results suggest that the effect of FGF on myogenic differentiation is mediated in
      part through inhibition of myogenin expression. These results demonstrate a
      direct role for endogenously synthesized growth factors in regulating myogenesis
      and provide support for a general role for related proteins in mammalian
      development.

PMID- 7515154
TI  - The genetic toxicology of N-nitrosodiphenylamine.

PMID- 7515148
TI  - Preferential deadenylation of Hsp70 mRNA plays a key role in regulating Hsp70
      expression in Drosophila melanogaster.
AB  - Following a standard heat shock, approximately 40% of Hsp70 transcripts in
      Drosophila melanogaster lack a poly(A) tail. Since heat shock disrupts other
      aspects of RNA processing, this observation suggested that heat might disrupt
      polyadenylation as well. We find, however, that as the temperature is increased a
      larger fraction of Hsp70 RNA is polyadenylated. Poly(A)-deficient Hsp70 RNAs
      arise not from a failure in polyadenylation but from the rapid and selective
      removal of poly(A) from previously adenylated transcripts. Poly(A) removal is
      highly regulated: poly(A) is (i) removed much more rapidly from Hsp70 RNAs than
      from Hsp23 RNAs, (ii) removed more rapidly after mild heat shocks than after
      severe heat shocks, and (iii) removed more rapidly after a severe heat shock if
      cells have first been conditioned by a mild heat treatment. Poly(A) seems to be
      removed by simple deadenylation rather than by endonucleolytic cleavage 5' of the
      adenylation site. During recovery from heat shock, deadenylation is rapidly
      followed by degradation. In cells maintained at high temperatures, however, the
      two processes are uncoupled and Hsp70 RNAs are deadenylated without being
      degraded. These deadenylated mRNAs are translated with low efficiency.
      Deadenylation therefore allows Hsp70 synthesis to be repressed even when
      degradation of the mRNA is blocked. Poly(A) tail shortening appears to play a key
      role in regulating Hsp70 expression.

PMID- 7515153
TI  - Genotoxicity and carcinogenicity of metronidazole.

PMID- 7515155
TI  - The genetic toxicology of toluene.

PMID- 7515156
TI  - Mutagenic activity of newly synthesized sulfa drugs to Salmonella typhimurium.
AB  - The mutagenic activity of seven newly synthesized sulfa drugs was studied in
      Salmonella typhimurium, using forward mutation to 8-azaguanine (8-AG) resistance
      and reversion mutation assays (Ames test) both in the absence and presence of
      Aroclor induced rat liver S9. In forward mutation assays, N1-methylsulfanilamide,
      N4-acetyl-N1-methylsulfanilamide and N4-acetyl-N1-diethylsulfanilamide were
      mutagenic to S. typhimurium TM677 both in the presence and absence of metabolic
      activation while N4-acetylsulfanilamide, N1-diethylsulfanilamide and 4-nitro-N-2
      pyridinylbenzenesulfonamide [2-(p-nitrobenzenesulfonamido)pyridine] were
      mutagenic only in the presence of metabolic activation. But 2-(N4
      acetylsulfanilamido)pyridine was mutagenic in neither the presence nor the
      absence of metabolic activation. However, none of the seven compounds had any
      mutagenic effect on S. typhimurium TA98 or TA100 in the absence or presence of
      metabolic activation, by the Ames test preincubation method. The relationship
      between the structure of the compounds and their mutagenic activity is also
      discussed.

PMID- 7515157
TI  - Studies on the mutagenicity of a peptoplast adhesive in Salmonella typhimurium.
AB  - A new class of adhesives--peptoplasts--was tested for their mutagenic potential
      in Salmonella typhimurium. The tested peptoplasts revealed no mutagenic
      properties under the present test conditions.

PMID- 7515158
TI  - Genotoxicity assay of five pesticides and their mixtures in Saccharomyces
      cerevisiae D7.
AB  - Four organophosphorus pesticides (azinphos-methyl, diazinone, dimethoate, and
      pirimiphos-methyl), and one carbamate (benomyl) were tested for cytotoxicity,
      reverse mutation and gene conversion in Saccharomyces cerevisiae D7, with and
      without the S9 metabolic system. Furthermore, two mixtures of the above
      compounds, namely benomyl + pirimiphos-methyl (6/1 ratio) and dimethoate +
      diazinone + azinphos-methyl (10/4/6 ratio) were tested in the same experimental
      model. Azinphos-methyl, benomyl, and pirimiphos-methyl alone did not induce any
      genotoxic effect, whereas azinphos-methyl and diazinone were active in inducing
      reversion and gene conversion. The benomyl + pirimiphos-methyl mixture did not
      show any genotoxic activity. The dimethoate + diazinone + azimphos-methyl mixture
      was genotoxic, although an antagonistic effect between the components was
      observed. The addition of S9 post-mitochondrial liver fraction decreased the
      activity of both single and mixed genotoxic agents.

PMID- 7515159
TI  - Genotoxicity of 1,3-dithiane and 1,4-dithiane in the CHO/SCE assay and the
      Salmonella/microsomal test.
AB  - 1,3-Dithiane and 1,4-dithiane are the sulfur-containing Maillard reaction
      products (MRPs) which have been found in boiled beef extracts. In this study the
      genotoxicity of these products was examined using the Salmonella/microsomal test
      and the CHO/SCE assay. 1,3-Dithiane showed a potent direct-acting mutagenicity
      toward S. typhimurium TA98 and TA100, but 1,4-dithiane had a lower mutagenicity
      toward both tester strains. Both compounds were shown to be non-mutagenic with
      hepatic metabolic activation with the exception of 1,3-dithiane toward strain
      TA100. To compare the mutagenic potential of 1,3-dithiane and 1,4-dithiane with
      other types of MRPs, 24 MRPs were examined for their mutagenicity to S.
      typhimurium TA98 and TA100 in the presence or absence of S9 mix. 2,6
      Dimethylpyrazine, furan, 2-acetylpyrrole, and thiazole were shown to be
      mutagenic. However, these four MRPs exhibited a lower mutagenicity in TA98 than
      1,3-dithiane and 1,4-dithiane. Furthermore, SCE frequencies in CHO cells were
      very significantly induced by 1,3-dithiane in the absence of S9 mix, but the SCE
      inducing capability of 1,3-dithiane was reduced or even disappeared with
      metabolic activation. 1,4-Dithiane did not significantly induce SCE frequencies
      in the presence or absence of S9 mix. Thus, we concluded that 1,3-dithiane was a
      potent mutagenic MRP in the Salmonella/microsomal test, whereas it was a weak SCE
      inducer in the CHO/SCE assay.

PMID- 7515160
TI  - Genetic safety evaluation of pesticides in different short-term tests.
AB  - Cyanazine, cyhexatin, dicamba and DNOC are pesticides commonly and broadly used
      in agriculture pest control. However, there is little information on their
      toxicity and mutagenicity in human cells and in whole animals. Therefore, UDS
      assay and SCE assay in human peripheral lymphocytes, and chromosome aberration
      analysis in bone marrow of rats have been used to assess the DNA-damaging
      activity of the above pesticides. Cyanazine proved non-genotoxic in all the test
      systems. Cyhexatin showed only weakly positive results for SCE induction in human
      lymphocytes, providing no concern for genotoxicological hazard. While dicamba did
      not show clastogenic effects in rodents, DNOC gave significant dose-related
      increases of structural chromosome aberrations in rat bone marrow cells. Female
      animals showed increased sensitivity to the toxic effects by DNOC at the highest
      dose. The results provide further information on the intrinsic genotoxic activity
      of the tested pesticides, which may contribute to the toxicological assessment of
      the risk associated with human exposure.

PMID- 7515161
TI  - Mutagenicity of tryptophan photoproducts in the Ames Salmonella assay.
AB  - During the photolysis of tryptophan a large number of products is formed. In this
      study, aqueous solutions of tryptophan were irradiated by ultraviolet light
      during 5, 20 or 40 h. Each of the irradiated batches was divided into two
      aliquots, which were freeze-dried or extracted with chloroform. For each batch
      the latter extract was subsequently divided into a purified chloroform extract
      and a methanol extract. Aliquots of the purified chloroform extracts were
      fractionated and pooled, peakwise, into seven fractions. A recombined sample was
      also constructed. All extracts and samples were tested for mutagenicity using the
      standard Ames Salmonella assay. The results indicate an exposure time dependent
      increase in mutagenicity of the extracts, as seen with tester strain TA100 both
      with and without metabolic activation. The mutagenicity of the freeze-dried
      extracts well approximated the mutagenicity of the chloroform extracts,
      indicating that most mutagenicity can be extracted with chloroform. With the
      fractions the highest mutagenic responses were seen in the late, i.e., less
      lipophilic fractions. This response pattern seen in TA98 and TA100, mainly with
      S9 activation, was in contrast to the response of TA102 without S9, which was
      highest to the more lipophilic fractions. On a fraction level, no general
      exposure dependent increase of mutagenicity was observed. The results also show
      that photooxidation of tryptophan gives rise to a different spectrum of products
      compared to pyrolysis. Both processes result in compounds with strong biological
      effects. Photooxidation results in compounds with low genotoxicity and high Ah
      receptor affinity while pyrolysis generates compounds with high genotoxicity and
      low or no Ah receptor affinity.

PMID- 7515162
TI  - Mutagenicity of ethanolic extracts of used acrylic dentures.
AB  - The in vivo physicochemical sorption of mutagenic substances onto acrylic
      polymers was investigated in worn acrylic dentures. Thus, ethanolic extracts of
      acrylic dentures from 41 of a total of 69 human donors (60%), were found
      mutagenic in the standard plate incorporation Salmonella mutagenicity test
      against either TA98 or TA100 strains. Denture extracts from smokers produced
      mutagenicity more often than the ones from non-smokers (75% vs. 45%, P 0.01).
      Mutagenicity was preferentially directed against TA98 (TA98:TA100 = 2.9:1, P <
      0.0005). Predilection for TA98 was more pronounced in denture extracts from non
      smokers (4.7:1) than from smokers (2.0:1). When direct mutagenicity was observed,
      it was reduced by the rat-liver S9. Induced mutant yields were 6.1 +/- 3.9 and
      7.0 +/- 8.9 times higher than the spontaneous for TA98 and TA100 respectively
      (smokers, 50-cm2 denture surface area eq./plate+S9). Denture extracts from
      smokers induced higher levels of mutation than the ones from non-smokers (TA98 +
      S9, smoker:non-smoker = 2:1, P < 0.01). Mutagenicity was associated with longer
      periods of denture usage (P 0.007). Thus, denture poly(methyl methacrylate) base
      material can adsorb mutagenic substances, possibly from diet and tobacco, which
      are extractable by ethanol. Theoretically, the in situ alcoholic desorption and
      recirculation of carcinogenic mutagens may have a contributory role in certain
      cases of intra-oral and upper alimentary tract carcinogenesis.

PMID- 7515163
TI  - Mutagenicity of coal-dust and smokeless-tobacco extracts in Salmonella
      typhimurium strains with differing levels of O-acetyltransferase activities.
AB  - Epidemiological studies have indicated an increased incidence of gastric
      neoplasia in coal miners. Because smokeless tobacco use is prevalent in the
      mining industry, nitrites or other components of these products may be
      etiologically associated with these gastric neoplasms. In this study both
      nitrosated and non-nitrosated coal-dust (from West Virginia and New Mexico) as
      well as smokeless-tobacco (snuff and chewing tobacco) extracts were examined for
      the presence of aromatic amines and nitroarenes by comparing the activities of
      these extracts in the pre-incubation variant of the Ames assay. Salmonella
      strains with differing O-acetyltransferase activities (TA98 and YG1024) were
      utilized in this investigation. The results of the examination of the coal-dust
      extracts indicated positive activity only in the nitrosated extracts. Both
      nitrosated extracts elicited an increased number of revertants (2-4-fold) on
      YG1024 without S9 in comparison to TA98, suggesting the presence of nitroarenes
      in these extracts. Additionally, the nitrosated West Virginia coal extract showed
      higher levels of activity on YG1024 with S9, indicating the possible presence of
      aromatic amines in this complex mixture. The non-nitrosated smokeless-tobacco
      extracts showed activity only on YG1024 in the presence of S9, with the highest
      amount of activity occurring in the snuff sample. Except for the chewing-tobacco
      extract on TA98 without S9, positive activity was found in both nitrosated
      tobacco extracts on YG1024 and TA98. As with the coal extracts, the presence of
      nitroarenes was inferred for these nitrosated materials. A comparative study of
      the non-nitrosated snuff extract across 5 tester strains with varying
      sensitivities to aromatic amines and nitroarenes (TA98NR, TA98/1,8-DNP6, TA98,
      YG1021 and YG1024) indicated that aromatic amines were a probable source of the
      mutagenic activity. The curing process and/or the addition of certain flavorants
      are potential sources of the mutagenic aromatic amines suggested to be present in
      the non-nitrosated snuff extract. These findings are consistent with an etiologic
      role supplementary to the nitroso compounds for mutagenic nitroarenes and
      aromatic amines in the development of gastric neoplasia in coal miners.

PMID- 7515164
TI  - Promethean viruses?

PMID- 7515166
TI  - Planar cobalt-57 bleomycin scintigraphy compared with CT-scan in the diagnosis
      and staging of lung cancer.
AB  - OBJECTIVES: Cobalt-57 bleomycin accumulates in tumour cells and is a diagnostic
      aid for discriminating malignant and benign lesions. Published data indicate that
      planar cobalt-57 bleomycin scintigraphy (bleo-scan) is a sensitive and specific
      test in the diagnosis and staging of lung cancer. CT-scan was however not used in
      these studies. We tested the value of bleo-scan and compared the results with
      those of computed tomography (CT-scan). METHODS: Bleo-scan and CT-scan were
      obtained from patients who were consecutively investigated because of a
      suspicious lesion on their chest X-ray. RESULTS: In 59 patients carcinoma of the
      lung was diagnosed 49 times (83%). The sensitivity of bleo-scan was 90%,
      specificity was 30% and positive predictive value (PPV) 86%. CT-scan could not
      discriminate between malignant and benign lesions. Thirty-two of the 41 patients
      with non-small-cell lung cancer had pathological examination of mediastinal lymph
      nodes, revealing metastases in 47% of the patients. Bleo-scan and CT-scan,
      respectively, had a sensitivity of 53 and 87%, a specificity of 77 and 82%, and
      negative predictive values (NPV) of 65 and 87%. In the 49 lung cancer patients
      distant metastases were detected at 11 sites in 10 patients. Bleo-scan gave false
      negative and false-positive results. CONCLUSIONS: Bleo-scan in (suspected) lung
      cancer adds too little to the diagnostic procedure to make it a routine
      procedure. CT-scan gives indispensable information about possible mediastinal
      involvement.

PMID- 7515170
TI  - Recombinant human granulocyte colony-stimulating factor in the management of
      cancer patients: five years on.
AB  - Recombinant human granulocyte colony-stimulating factor (G-CSF) has been used
      worldwide in cancer patients for over 1 year, and (only 5 years from the first
      publication on the clinical use of this growth factor) experience is rapidly
      accumulating in many oncological situations. Several randomized studies have
      confirmed its value in allowing the optimal delivery of chemotherapy without
      undue dose reductions or dose delays, while at the same time reducing the overall
      risks of febrile neutropenia associated with the use of cytotoxic chemotherapy.
      Its virtual lack of significant side effects, its selectivity of action, its
      rapid effect on neutrophil kinetics (reducing both the maturation and release
      times of bone marrow neutrophils to 1-2 days rather than the normal 4-5 days),
      and the reproducible augmentation of neutrophil production in several neoplastic
      and nonneoplastic situations, as well as the activation of myeloid cell
      functions, have made G-CSF the growth factor of choice in most cancer units. Some
      of the published information regarding its current and potential use in the
      management of oncological patients is summarized here.

PMID- 7515167
TI  - Clinical application of cytokines for cancer treatment.
AB  - As the introduction to a special issue of Oncology on the role of cytokines for
      cancer treatment, this article summarizes their various current uses.
      Interferons, interleukin-2 and hematopoietic factors are extensively used for the
      treatment of hematopoietic as well as nonhematopoietic malignancies, either as
      the main therapeutic agents or as an adjuvant. Combined usage of several
      cytokines, or cytokines and chemotherapeutic agents has been tried. Research on
      gene therapy using cytokines is in progress and expected to become a future
      modality of cytokine usage in cancer treatment.

PMID- 7515171
TI  - Stem cell factor is a potent synergistic factor in hematopoiesis.
AB  - Stem cell factor (SCF), a ligand for c-kit, has a broad range of activities
      including effects on cells at or near the level of the multipotential stem cell
      as well as on committed cells. Preclinical studies show that SCF can protect
      against lethal irradiation, elicit multilineage responses in peripheral blood and
      bone marrow cellularity, and increase circulating peripheral blood progenitor
      cells (PBPC) in a dose-dependent manner. Recombinant human SCF has major clinical
      potential through its synergy with other factors, especially recombinant human
      granulocyte colony-stimulating factor, to enhance mobilization of PBPC.

PMID- 7515169
TI  - Interferons for the treatment of hematological malignancies.
AB  - Interferon (IFN) has diverse activities against the proliferation and function of
      various tumor cells. Recently, IFN-alpha has been widely used in the treatment of
      several hematological malignancies including chronic myelogenous leukemia (CML),
      multiple myeloma, and hairy cell leukemia. IFN-alpha is becoming a first-choice
      drug in the treatment of CML, because it has been reported to suppress or abolish
      the Ph1 chromosome in CML patients. IFN-alpha is used in combination with
      conventional chemotherapeutic regimens in the treatment of multiple myeloma.
      There are many ongoing trials that include IFN-alpha in their regimens to
      determine whether or not the prognosis of multiple myeloma can be improved.
      Although the precise mechanism of the action of IFN has not been fully explained,
      the clinical applications of IFN for various hematological malignancies are
      expanding.

PMID- 7515168
TI  - Interferons in the therapy of solid tumors.
AB  - Interferons, a group of naturally occurring proteins, possess potent
      immunological effects. The availability of large amounts of purified interferon
      through recombinant DNA technology has led to the testing of these agents against
      a number of tumor types. Interferon-alpha has been the most widely studied. The
      most encouraging results have been observed in the treatment of melanoma among
      nonhematological neoplasms, and in the locoregional treatment of other tumor
      types. It is hoped that further research into the use of the interferons, both
      singly and in combination with chemotherapy and other immunological agents, will
      lead to a better elucidation of their therapeutic role against cancer. In this
      article, the use of interferons in the treatment of solid tumors is reviewed.

PMID- 7515165
TI  - Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants.
AB  - Most asymptomatic individuals infected with HIV-1 have a cytotoxic T lymphocyte
      (CTL) response to the virus Gag proteins which can be demonstrated in vitro.
      Epitopes have been mapped in p17 Gag and p24 Gag restricted by HLA-B8 (p17-3 and
      p24-13) and -B27 (p24-14). Viruses isolated from patients who make CTL responses
      to these peptides vary within the genetic sequences encoding these epitopes and
      some mutations lead to reduction in killing activity in vitro. This was
      attributed to either failure of the variant epitope to bind major
      histocompatibility complex class I or failure of T-cell receptors to bind the
      presented peptide. But peptide variants of class I-restricted epitopes cause
      'antagonism', that is, the presence of a variant epitope (in the form of peptide)
      inhibits normal lysis of targets presenting the original epitope. This mirrors
      similar findings in class II-restricted systems. Here we report that naturally
      occurring variant forms of p17-3, p24-13 and p24-14 may cause antagonism of CTL
      lines derived from the same individuals. The effect is present if the epitopes
      are derived from synthetic peptides and when they are processed from full-length
      proteins expressed by either recombinant vaccinia constructs or replicating HIV.

PMID- 7515175
TI  - [In situ hybridization. Theoretical principles and practical applications].
AB  - In situ hybridisation is a sensitive and reliable technique for the demonstration
      of DNA- or mRNA-sequences on histological tissue preparations. This review deals
      with the theoretical background as well as the benefits and limitations of the
      method; additionally the value of in situ hybridisation as a tool in routine
      diagnostic pathology is briefly described.

PMID- 7515172
TI  - Carcinoembryonic antigen staining patterns at the invasive tumor margin predict
      the malignant potential of colorectal carcinoma.
AB  - Immunohistochemical carcinoembryonic antigen (CEA) staining patterns at the
      invasive tumor margin were correlated with malignant potential in 64 advanced
      colorectal carcinomas. Twenty-two (34%) carcinomas showed an apical and 42 (66%)
      a cytoplasmic staining pattern. Carcinomas with a cytoplasmic pattern had a
      higher incidence of lymph node (71 versus 41%; p < 0.05) and liver (50 versus
      23%; p < 0.05) metastasis and higher levels of serum CEA (p < 0.01) than those
      with an apical staining pattern. Nine of 11 recurrent tumors had a cytoplasmic
      pattern and 2 had an apical pattern (p < 0.05). Among carcinomas having the same
      degree of differentiation, those with a cytoplasmic CEA staining pattern were
      more aggressive. Six (55%) well-differentiated carcinomas with a cytoplasmic
      pattern metastasized to the liver while none with an apical pattern did (p <
      0.05). Moderately differentiated carcinomas with a cytoplasmic pattern had a
      significantly higher incidence of lymph node metastasis than those with an apical
      pattern (77 versus 46%; p < 0.05). When colorectal carcinomas are examined at the
      invasive tumor margin, an evaluation of the CEA staining pattern is useful in
      recognizing carcinomas having a higher potential to metastasize and recur after
      curative surgery.

PMID- 7515173
TI  - Indocyanine green dye-enhanced diode laser photocoagulation of poorly defined
      subfoveal choroidal neovascularization.
AB  - Indocyanine green (ICG) is a dye with an absorption peak (795 to 810 nm) similar
      to the emission peak of the diode laser (805 nm). Therefore, ICG dye-enhanced
      diode laser photocoagulation may permit the selective ablation of ICG-retaining
      choroidal neovascular membranes (CNVM) with relative sparing of the neighboring
      neurosensory retina. Ten patients with poorly defined subfoveal CNVM were treated
      with ICG dye-enhanced diode laser photocoagulation and followed for an average of
      15 months. One of the 10 patients experienced an immediate significant drop in
      visual acuity after photocoagulation. Obliteration of the CNVM at the site of
      laser photocoagulation was confirmed by fluorescein angiography and ICG
      angiography. Subfoveal chorioretinal scar formation was noted postoperatively in
      all 10 patients. At last follow up, 9 of these 10 patients had no more than a two
      line increase or decrease in visual acuity. These preliminary results suggest
      that poorly defined subfoveal CNVM can be successfully treated by ICG dye
      enhanced diode laser photocoagulation with minimal adverse affect on visual
      acuity in most cases.

PMID- 7515174
TI  - Prolonged mechanical ventilation in children.
AB  - Improvements in neonatal and pediatric intensive care have produced a growing
      population of children dependent on mechanical ventilation for survival. Long
      term mechanical ventilation has become a realistic alternative to death from
      progressive respiratory failure for many children with chronic respiratory
      illness. This article reviews the pathophysiology, etiology, and management of
      chronic respiratory failure in childhood.

PMID- 7515177
TI  - TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase
      PKR.
AB  - A cDNA encoding a double-stranded-RNA (dsRNA)-binding protein was isolated by
      screening a HeLa cell cDNA expression library for proteins that bind the HIV-1
      Rev-responsive-element RNA. The cDNA encoded a protein that was identical to
      TRBP, the previously reported cellular protein that binds the transactivation
      response element (TAR) RNA of human immunodeficiency virus type 1. TRBP inhibited
      phosphorylation of the interferon-induced ribosome-associated protein kinase PKR
      and of the eukaryotic translation initiation factor eIF-2 alpha in a transient
      expression system in which the translation of a reporter gene was inhibited by
      the localized activation of PKR. TRBP expression in HeLa cells complemented the
      growth and protein-synthesis defect of a vaccinia virus mutant lacking the
      expression of the dsRNA-binding protein E3L. These results implicate TRBP as a
      cellular regulatory protein that binds RNAs containing specific secondary
      structure(s) to mediate the inhibition of PKR activation and stimulate
      translation in a localized manner.

PMID- 7515178
TI  - Functional unit size of the charybdotoxin receptor in smooth muscle.
AB  - Target inactivation analysis was used to determine the functional size of the
      charybdotoxin (ChTX) receptor in aortic and tracheal sarcolemmal membrane
      vesicles. This receptor has previously been shown to be an integral component of
      the high-conductance Ca2+-activated K+ (Maxi-K) channel in these smooth muscles.
      Exposure of either bovine aortic or bovine tracheal sarcolemma to high-energy
      irradiation results in disappearance of 125I-labeled ChTX binding activity as a
      monoexponential function of radiation dose; from these functions molecular masses
      of 88 +/- 10 kDa and 89 +/- 6 kDa, respectively, can be calculated. Similar
      results were obtained from radiation inactivation studies with the detergent
      solubilized ChTX receptor from aortic sarcolemmal membranes. The effect of
      radiation on 125I-labeled ChTX binding is to decrease the number of functional
      ChTX receptors without affecting the affinity of receptors for the toxin,
      indicating that radiation is destroying, rather than altering, the binding site.
      The validity of the radiation inactivation technique in these membrane
      preparations is supported by data obtained in parallel experiments in which
      target sizes of the alpha 1 subunit of the L-type Ca2+ channel and 5'
      nucleotidase were measured. The molecular masses determined for these entities
      are in excellent agreement with those expected from previous studies. The present
      data are discussed in terms of the recently determined subunit composition of the
      smooth muscle Maxi-K channel. In light of the target size, a single alpha beta
      subunit heterodimer complex could serve as the ChTX receptor.

PMID- 7515179
TI  - Persistent increase of hippocampal presynaptic axon excitability after repetitive
      electrical stimulation: dependence on N-methyl-D-aspartate receptor activity,
      nitric-oxide synthase, and temperature.
AB  - The electrical excitability of Schaffer collateral axons and/or terminals was
      studied in hippocampal slices by monitoring single, CA3 pyramidal neurons
      activated antidromically from CA1 stratum radiatum. At 22 degrees C, weak,
      repetitive stimulation with as few as 10 impulses at 2 Hz led to a robust
      lowering of the antidromic activation threshold that lasted > 30 min. The effect
      was completely absent at 32 degrees C and was blocked by both the N-methyl-D
      aspartate receptor antagonist, 2-amino-5-phosphonovalerate and the inhibitor of
      nitric-oxide synthase, L-nitro-arginine methyl ester. Such threshold lowering
      would alter the variance of synaptic responses from axons stimulated in the
      variable excitation region of their input-output functions. These results thus
      raise important doubts about the interpretation of experiments in which the so
      called minimal-stimulation method has been used at reduced temperature to infer
      changes in quantal transmission during hippocampal long-term potentiation. In the
      present experiments, no changes were observed in the estimate of excitatory
      postsynaptic potential quantal content in long-term potentiation experiments at
      either temperature, which could not be accounted for by an artificial,
      temperature-dependent change in the responsiveness of presynaptic axons.

PMID- 7515176
TI  - Regulation of the gating of cystic fibrosis transmembrane conductance regulator
      C1 channels by phosphorylation and ATP hydrolysis.
AB  - Opening of cystic fibrosis transmembrane conductance regulator (CFTR) Cl channels
      requires their phosphorylation by protein kinase A followed by exposure to ATP.
      We examined the interaction between nucleotides and phosphorylated CFTR channels
      by recording currents in intact cardiac myocytes and in excised patches. We found
      that, although the hydrolysis-resistant ATP analogue 5'-adenosine(beta,gamma-
      imino)triphosphate (AMP-PNP) cannot open phosphorylated CFTR channels, it can
      cause channels opened by ATP to remain open for many minutes. This suggests that
      ATP action at one site on CFTR is a prerequisite for AMP-PNP action at a second
      site. However, this action of AMP-PNP is restricted to highly phosphorylated CFTR
      channels, which, in the presence of ATP, display a relatively high open
      probability, but is not seen in partially phosphorylated CFTR channels, which
      have a low open probability in the presence of ATP. Our findings argue that
      incremental phosphorylation differentially regulates the interactions between
      nucleotides and the two nucleotide binding domains of CFTR. The nature of those
      interactions suggests that ATP hydrolysis at one nucleotide binding domain
      controls channel opening and ATP hydrolysis at the other regulates channel
      closing.

PMID- 7515180
TI  - A helical-dipole model describes the single-channel current rectification of an
      uncharged peptide ion channel.
AB  - We are designing simple peptide ion channels as model systems for the study of
      the physical principles controlling conduction through ion-channel proteins. Here
      we report on an uncharged peptide, Ac-(Leu-Ser-Ser-Leu-Leu-Ser-Leu)3-CONH2,
      designed to form an aggregate of parallel, amphiphilic, membrane-spanning alpha
      helices around a central water-filled pore. This peptide in planar lipid bilayers
      forms ion channels that show single-channel current rectification in symmetric 1
      M KCl. The current at a given holding membrane potential is larger than the
      current measured through the same channel when the potential is reversed. Based
      on our hypothesized gating mechanism, the larger currents flow from the peptide
      carboxyl terminus toward the amino terminus. We present an ionic electrodiffusion
      model based on the helical-dipole potential and the dielectric interfacial
      polarization energy, which with reasonable values for dipole magnitude and
      dielectric constants, accurately replicates the current-voltage data.

PMID- 7515181
TI  - Direct binding of myelin basic protein and synthetic copolymer 1 to class II
      major histocompatibility complex molecules on living antigen-presenting cells-
      specificity and promiscuity.
AB  - Copolymer 1 (Cop 1) is a synthetic basic random copolymer of amino acids that has
      been shown to be effective in suppression of experimental allergic
      encephalomyelitis and is being tested as a candidate drug for multiple sclerosis.
      It has been previously demonstrated that Cop 1 is immunologically cross-reactive
      with the autoantigen myelin basic protein (BP) and competitively inhibits the
      response to BP of T-cell lines and clones of different major histocompatibility
      complex (MHC) restrictions, of both mouse and human origin. In the present study
      we demonstrated the direct binding of Cop 1, using its biotinylated derivative,
      to MHC molecules on living antigen-presenting cells. Binding of biotinylated BP
      and peptide p84-102 (an immunodominant epitope of BP) was also demonstrated. Cop
      1 and BP bound in a promiscuous manner to different types of antigen-presenting
      cells of various H-2 and HLA haplotypes. The specificity of the binding was
      confirmed by its inhibition with either the relevant anti-MHC class II antibodies
      or unlabeled analogs. Cop 1 exhibited the most extensive and fast binding to
      antigen-presenting cells. In addition, Cop 1 inhibited the binding of
      biotinylated derivatives of BP and of p84-102 to the MHC class II molecules and
      even displaced these antigens when already bound. Thus, these results suggest
      that Cop 1 indeed competes with BP for MHC binding and, thereby, inhibits T-cell
      responses to BP. The binding of Cop 1 to different DR alleles, probably because
      of its multiple MHC binding motifs, may indicate its potential as a broad
      spectrum drug for multiple sclerosis.

PMID- 7515183
TI  - Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity.
AB  - To investigate the mechanisms of T-cell-mediated cytotoxicity, we estimated the
      involvement of apoptosis-inducing Fas molecule on the target cells and its ligand
      on the effector cells. When redirected by ConA or anti-CD3 monoclonal antibody, a
      CD4+ T-cell clone, BK1, could lyse the target cells expressing wild-type Fas
      molecule but not those expressing death signaling-deficient mutants. This
      indicates the involvement of Fas-mediated signal transduction in the target cell
      lysis by BK1. Anti-CD3-activated but not resting BK1 expressed Fas ligand as
      detected by binding of a soluble Fas-Ig fusion protein, and the BK1-mediated
      cytotoxicity was blocked by the addition of Fas-Ig, implicating the inducible Fas
      ligand in the BK1 cytotoxicity. Ability to exert the Fas-mediated cytotoxicity
      was not confined to BK1, but splenic CD4+ T cells and, to a lesser extent, CD8+ T
      cells could also exert the Fas-dependent target cell lysis. This indicates that
      the Fas-mediated target cell lytic pathway can be generally involved in the T
      cell-mediated cytotoxicity. Interestingly, CD4+ T cells prepared from gld/gld
      mice did not mediate the Fas-mediated cytotoxicity, indicating defective
      expression of functional Fas ligand in gld mice.

PMID- 7515184
TI  - Transcellular water transport in lung alveolar epithelium through mercury
      sensitive water channels.
AB  - The movement of water between the air space and capillary compartments is
      important for the maintenance of air space hydration during respiration and for
      reabsorption of excess alveolar fluid. We have obtained immunocytochemical and
      functional evidence that plasma-membrane water channels are responsible for water
      transport in the intact lung. Northern and quantitative immunoblot analysis
      showed high expression of CHIP28 (channel-forming integral membrane protein of 28
      kDa) water channels in rat lung; immunocytochemistry showed CHIP28 localization
      to epithelial cell plasma membranes. Stopped-flow light scattering measurements
      of osmotic water permeability (Pf) in freshly isolated rat alveolar type II
      epithelial cells indicated a high Pf of 0.015 +/- 0.002 cm/s (10 degrees C) that
      was weakly temperature-dependent (activation energy, 4 kcal/mol) and reversibly
      inhibited by 78 +/- 4% by 0.5 mM HgCl2. An in situ-perfused sheep lung model was
      used to determine the route for water movement in intact lung. Blood-to-air-space
      water transport was measured by sampling air space fluid after instillation into
      distal air spaces of hyperosmolar saline (900 mOsm) containing radioiodinated
      albumin and [14C]mannitol. In seven sets of experiments, air space osmolality and
      radioiodinated albumin equilibrated with a t1/2 of 0.85 +/- 0.1 min. In the
      contralateral lung perfused with 0.5 mM HgCl2, t1/2 increased to 2.7 +/- 0.4 min;
      the inhibitory effect of HgCl2 was fully reversed by 5 mM 2-mercaptoethanol.
      These results provide direct evidence for transcellular movement of water across
      the alveolar epithelium in intact lung through mercury-sensitive water channels.

PMID- 7515185
TI  - Solution NMR structure of the major cold shock protein (CspA) from Escherichia
      coli: identification of a binding epitope for DNA.
AB  - Sequence-specific 1H and 15N resonance assignments have been determined for the
      major cold shock protein (CspA) from Escherichia coli with recently developed
      three-dimensional triple-resonance NMR experiments. By use of these assignments,
      five antiparallel beta-strands were identified from analysis of NMR data. Strands
      1-4 have a classical 3-2-1-4 Greek key beta-sheet topology and there are two beta
      bulges, at positions Lys10-Trp11 and Gly65-Asn66. Three-dimensional structures of
      CspA were generated from NMR data by using simulated annealing with molecular
      dynamics. The overall chain fold of CspA is a beta-barrel structure, with a
      tightly packed hydrophobic core. Two-dimensional isotope-edited pulsed-field
      gradient 15N-1H heteronuclear single-quantum coherence spectroscopy was used to
      characterize the 15N-1H fingerprint spectrum with and without a 24-base
      oligodeoxyribonucleotide, 5'-AACGGTTTGACGTACAGACCATTA-3'. Protein-DNA complex
      formation perturbs a subset of the amide resonances that are located mostly on
      one face of the CspA molecule. This portion of the CspA molecular surface
      includes two putative RNA-binding sequence motifs which contribute to an unusual
      cluster of eight surface aromatic side chains: Trp11, Phe12, Phe18, Phe20, Phe31,
      His33, Phe34, and Tyr42. These surface aromatic groups, and also residues Lys16,
      Ser44, and Lys60 located on this same face of CspA, are highly conserved in the
      family of CspA homologues. These isotope-edited pulsed-field gradient NMR data
      provide a low-resolution mapping of a DNA-binding epitope on CspA.

PMID- 7515182
TI  - Sensitivity of wild-type human immunodeficiency virus type 1 reverse
      transcriptase to dideoxynucleotides depends on template length; the sensitivity
      of drug-resistant mutants does not.
AB  - Analysis of the three-dimensional structure of human immunodeficiency virus type
      1 (HIV-1) reverse transcriptase (RT) complexed with double-stranded DNA indicates
      that while many nucleoside-resistance mutations are not at the putative dNTP
      binding site, several are in positions to interact with the template-primer. Wild
      type HIV-1 RT and two nucleoside-resistant variants, Leu74-->Val and Glu89-->Gly,
      have been analyzed to determine the basis of resistance. The ability of the wild
      type enzyme to incorporate, or reject, a 2',3'-dideoxynucleoside triphosphate
      (ddNTP) is strongly affected by interactions that take place between the enzyme
      and the extended template strand 3-6 nt beyond the polymerase active site.
      Inspection of a model of the enzyme with an extended template suggests that this
      interaction involves the fingers subdomain of the p66 subunit in the vicinity of
      Leu74. These data provide direct evidence that the fingers subdomain of the p66
      subunit of HIV-1 RT interacts with the template strand. The wild-type enzyme is
      resistant to ddITP if the template extension is 3 nt or less and becomes
      sensitive only when the template extends more than 3 or 4 nt beyond the end of
      the primer strand. However, the mutant enzymes are resistant with both short and
      long template extensions. Taken together with the three-dimensional structure of
      HIV-1 RT in complex with double-stranded DNA, these data suggest that resistance
      to the dideoxynucleotide inhibitors results from a repositioning or change in the
      conformation of the template-primer that alters the ability of the enzyme to
      select or reject an incoming dNTP.

PMID- 7515186
TI  - Three-dimensional working model of M1 RNA, the catalytic RNA subunit of
      ribonuclease P from Escherichia coli.
AB  - A three-dimensional model of M1 RNA, the catalytic RNA subunit of RNase P from
      Escherichia coli, was constructed with the aid of a computer. The modeling
      process took into account data from chemical and enzymatic protection
      experiments, phylogenetic analysis, studies of the activities of mutants, and the
      kinetics of reactions catalyzed by the binding of substrate to M1 RNA. The model
      provides a plausible picture of the binding to M1 RNA of the tRNA domain of a
      precursor tRNA substrate. The scissile bond and adjacent segments of the
      aminoacyl acceptor stem of a precursor tRNA substrate can fit into a cleft that
      leads to the phylogenetically conserved, central part of the structure.

PMID- 7515187
TI  - Costimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue
      and in conjunction with tumor necrosis factor alpha leads to autoimmunity in
      transgenic mice.
AB  - Tolerance to peripheral antigens is thought to result from the inability of
      parenchymal tissue to stimulate T cells--an inability that is believed to relate
      to the lack of expression of the costimulatory signal(s) required for T-cell
      activation. To test this model, we generated transgenic mice expressing
      costimulatory molecule B7-1 on the B cells of the pancreas. We find that islets
      from these transgenic mice are immunogenic for naive T cells in vitro and in
      vivo. Nonetheless, mice expressing the costimulator B7-1 specifically on beta
      cells do not develop diabetes, suggesting that expression of the B7-1
      costimulator is not sufficient to abrogate the tolerance to peripheral antigens.
      We have reported that tumor necrosis factor alpha subunit (TNF-alpha) expressed
      by beta cells leads to a local inflammation but no islet destruction. Strikingly,
      however, the combination of a local inflammation due to the expression of the
      cytokine TNF-alpha and the expression of B7-1 results in tissue destruction and
      diabetes.

PMID- 7515188
TI  - Rapid endocytosis of the cystic fibrosis transmembrane conductance regulator
      chloride channel.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel
      is found at the apical region of exocrine epithelial cells, both at the cell
      surface and in an apically localized intracellular compartment. To determine if
      this internal pool was due to endocytosis, a technique was developed that allows
      the rate of CFTR internalization from the cell surface to be monitored. A two
      step periodate/hydrazide biotinylation procedure was used to derivatize cell
      surface glycoconjugates. Because both of these steps are required for
      derivatization and are conducted at 4 degrees C, the inclusion of a 37 degrees C
      incubation between the treatments resulted in an assay for the internalization of
      cell surface glycoconjugates. CFTR was found to be targeted to a rapidly
      recycling endocytic pathway, as approximately 50% of cell surface CFTR was
      internalized within minutes and unavailable for biotinylation. In contrast, the
      major glycoproteins of the apical surface were not significantly endocytosed
      during even longer incubations at 37 degrees C. Elevating cAMP levels either by
      forskolin or cAMP analogs, which has been shown to activate CFTR chloride channel
      activity, inhibited CFTR internalization. However, cAMP did not affect the
      internalization of G551D CFTR, a naturally occurring Gly-551-->Asp mutant that is
      expressed at the cell surface but lacks normal ion-channel function. In addition,
      the inhibition by cAMP of CFTR was not observed when cells were depleted of
      cellular chloride. The presence of CFTR in epithelial cells had previously been
      shown to confer a cAMP-mediated inhibition on the rate of fluid-phase
      endocytosis. This effect was not seen in chloride-depleted cells, suggesting that
      CFTR's ion-channel function and localization to incipient endosomes may be
      responsible for the observed inhibition. The finding that CFTR is targeted to the
      endocytic pathway may provide insight into the role of CFTR in normal exocrine
      function. In addition, these findings suggest that the expression of a regulated
      ion channel in a membranous subcellular compartment provides a mechanism by which
      a cell can regulate vesicular trafficking through that compartment.

PMID- 7515189
TI  - Induction of calcium-dependent nitric oxide synthases by sex hormones.
AB  - We have examined the effects of pregnancy and sex hormones on calcium-dependent
      and calcium-independent nitric oxide synthases (NOSs) in the guinea pig.
      Pregnancy (near term) caused a > 4-fold increase in the activity of calcium
      dependent NOS in the uterine artery and at least a doubling in the heart, kidney,
      skeletal muscle, esophagus, and cerebellum. The increase in NOS activity in the
      cerebellum during pregnancy was inhibited by the estrogen-receptor antagonist
      tamoxifen. Treatment with estradiol (but not progesterone) also increased calcium
      dependent NOS activity in the tissues examined from both females and males.
      Testosterone increased calcium-dependent NOS only in the cerebellum. No
      significant change in calcium-independent NOS activity was observed either during
      pregnancy or after the administration of any sex hormone. Both pregnancy and
      estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS
      in skeletal muscle, suggesting that the increases in NOS activity result from
      enzyme induction. Thus both eNOS and nNOS are subject to regulation by estrogen,
      an action that could explain some of the changes that occur during pregnancy and
      some gender differences in physiology and pathophysiology.

PMID- 7515190
TI  - [Treatment of clozapine-induced agranulocytosis with granulocyte colony
      stimulating factor G-CSF].

PMID- 7515192
TI  - Utility of fragmented human fetal tissue as a potential dopaminergic brain graft
      in Parkinson's disease.
AB  - There is increasing interest in the use of human fetal dopaminergic tissue as a
      source of striatal transplant in parkinsonian patients. This tissue is acquired
      by elective abortions. The possibilities of the use of this tissue were studied
      by macroscopical examination, cell-culturing followed by immunohistochemical
      staining and by high performance liquid chromatography. It turned out that 50% of
      the curettages obtained by suction abortion were too fragmented to reliably
      recognize the dopamine-containing area (ventral mesencephalon). Furthermore,
      dissection of the brainstem immediately after the abortion procedure seemed to be
      of utmost importance.

PMID- 7515191
TI  - A new pictorial instrument for child and adolescent psychiatry: a pilot study.
AB  - A pictorial instrument was developed to assess psychopathology in children aged 6
      to 16 years. Symptom pictures (n = 137) representing DSM-III-R criteria were
      organized into seven diagnostic subscales. Clarity of the pictures was assessed
      in 31 normal children. Fifty-one psychiatric inpatient children completed the
      instrument using a 6-point visual analogue scale. Sensitivity to change was
      assessed in 15 children. The subscales' internal consistencies (Cronbach's alpha)
      ranged from 0.54 to 0.86. A canonical discriminant analysis among four diagnostic
      groups achieved a Wilks' lambda of 0.67 (p = 0.02). This instrument may be a
      valuable adjunct to psychiatric interviews in children.

PMID- 7515193
TI  - Effect of reduced aprotinin dosage on blood loss and use of blood products in
      patients undergoing cardiopulmonary bypass.
AB  - High-dose aprotinin reduces bleeding after cardiac surgery, but has also evoked
      concern with regard to potential side effects and hospital costs. To evaluate the
      effects of reduced-dose aprotinin on blood loss and need for blood transfusion,
      40 patients undergoing myocardial revascularization were studied (double-blind,
      placebo-controlled). Postoperative bleeding was reduced by 40% and erythrocyte
      infusion by 85% in the group given 3 x 10(6) KIU aprotinin (1 x 10(6) as a
      loading dose before cardiopulmonary bypass, 1 x 10(6) in the priming volume and
      2.5 x 10(5)/hour intraoperatively) Aprotinin concentrations during the operation
      were monitored and maintained above the required level. There were no adverse
      effects of the drug. Hospital expenditure on blood products was reduced by 51%
      when aprotinin was used. Our study suggests that aprotinin in reduced dosage
      diminishes bleeding and requirements for blood products, and that it should be
      given before, during and after cardiopulmonary bypass.

PMID- 7515196
TI  - Possible roles for anti- or pro-inflammatory therapies in the management of
      sepsis.
AB  - In the past few years we have greatly improved our understanding of the
      pathophysiologic mechanisms underlying the clinical syndrome of sepsis. As of
      this writing, however, this improved understanding has failed to result in the
      development of a single pharmacologic agent with clearly documented efficacy for
      improving outcome in septic patients. Research in this field, however, is
      yielding new insights on almost a daily basis, and it seems probable that the
      pharmacotherapy of sepsis and septic shock will undergo dramatic changes in the
      near future.

PMID- 7515194
TI  - Inhibition of hepatic chylomicron remnant uptake by gene transfer of a receptor
      antagonist.
AB  - The low density lipoprotein receptor-related protein (LRP) has been proposed to
      mediate in concert with the LDL receptor (LDLR) the uptake of dietary
      lipoproteins into the hepatocytes. This hypothesis was tested by transient
      inactivation of LRP in vivo. Receptor-associated protein (RAP), a dominant
      negative regulator of LRP function, was transferred by an adenoviral vector to
      the livers of mice lacking LDLR (LDLR-/-). The inactivation of LRP by RAP was
      associated with a marked accumulation of chylomicron remnants in LDLR-/- mice and
      to a lesser degree in normal mice, suggesting that both LDLR and LRP are involved
      in remnant clearance.

PMID- 7515195
TI  - [Pulmonary mucormycosis in leukemic patients. Apropos of 2 cases].
AB  - Mucormycosis is a rare fungal infection that has been described mainly in
      oncologic and diabetic patients. We here report the cases of two leukaemic
      patients in whom pulmonary mucormycosis was diagnosed. Prompt diagnosis, therapy
      with amphotericin B and surgery when possible, are the cornerstones in the
      treatment of this fungal infection. Although infrequent, this infection must be
      suspected in oncohaematological patients with lung infiltrates.

PMID- 7515198
TI  - Desensitization and noncompetitive blockade of GABAA receptors in ventral
      midbrain neurons by a neurosteroid dehydroepiandrosterone sulfate.
AB  - Dehydroepiandrosterone sulfate (DHEAS) blocked the GABAA receptor
      noncompetitively in neurons grown in primary culture from the ventral midbrains
      of fetal rats. The apparent dissociation constant for this blockade was 4.5
      microM, and one molecule of DHEAS was sufficient to block the receptor. The
      affinity of the blocked receptor for GABA was diminished by about one half. The
      findings that the DHEAS caused no rectification of chloride currents and that it
      did not shorten the durations of open ion channels indicated that DHEAS did not
      act by occluding open ion channels. Neither did it diminish their conductance.
      DHEAS accelerated desensitization in at least one population of receptors,
      diminished the amplitudes of inhibitory postsynaptic currents, and shortened
      their decay time constants in a concentration dependent manner.

PMID- 7515197
TI  - Prostate cancer screening before and after abdominoperineal resection:
      recommendations, biopsy, and therapeutic techniques.
AB  - BACKGROUND: The purpose of this study was to determine the incidence and
      mortality rate of prostate cancer in men without a rectum at a single
      institution. The usefulness of serum prostate specific antigen (PSA) to screen
      for prostate cancer in men without a rectum was defined. Improved biopsy
      techniques and therapeutic options were developed in those with elevated levels.
      METHODS: We undertook a retrospective review of 65 men who underwent an
      abdominoperineal resection. Twenty-five of these men underwent serum PSA
      determinations (mean age, 68 years). RESULTS: Four (16%) of 25 patients had
      elevated PSA levels. Three of these four men and two additional patients (one
      before the availability of PSA and one with normal serum PSA level) were found to
      have biopsy-proven prostate cancer. Two men (3% of the 65 patient population)
      died of metastatic prostate cancer. CONCLUSIONS: We believe that men about to
      undergo an abdominoperineal resection should have a preoperative serum PSA
      measurement. Moreover, we recommend that men older than 49 years of age (older
      than 39 years for those with positive family histories) without a rectum should
      have annual serum PSA determinations as if recommended for the general male
      population at large. If an elevated serum PSA level is discovered, the
      transperineal ultrasonogram-guided biopsy technique offers an effective method to
      detect peripheral zone prostate cancers.

PMID- 7515200
TI  - Protection of porcine aortic endothelial cells from complement-mediated cell
      lysis and activation by recombinant human CD59.
AB  - Discordant xenogeneic organ transplantation is a potential solution to the
      critical shortage of suitable donor organs. However, clinical application of
      xenotransplantation with physiologically suitable organs such as those from the
      pig, is currently limited by the lack of agents to prevent antibody and
      complement-mediated hyperacute rejection of the transplanted organ. We have used
      retrovirus-mediated gene transfer to express the terminal complement inhibitor
      protein, human CD59, in neonatal porcine aortic endothelial cells (nPAEC). Human
      CD59 was constitutively expressed in nPAECs at levels similar to that of native
      CD59 in human umbilical vein endothelial cells. The protein was tethered to the
      cell surface by a glycosyl-phosphatidylinositol anchor, as demonstrated by its
      removal following treatment with phosphatidylinositol-specific phospholipase C.
      In a model of antibody-dependent complement activation, nPAECs expressing human
      CD59 were protected from membrane pore formation and cell lysis by complement
      derived from either human or baboon sera. Conversely, nPAECs expressing CD59 were
      not protected from lysis by rabbit or dog complement, indicating that recombinant
      CD59 retained its species-restricted inhibitory activity. Additionally, CD59
      expressed on nPAECs inhibited the C5b-9-dependent generation of membrane
      prothrombinase activity. Collectively, these data establish that stable
      expression of human CD59 on xenotypic (porcine) endothelial cells renders these
      cells resistant to both the cytolytic and procoagulant effects of human
      complement. We propose that expression of recombinant human CD59 on porcine donor
      organs may prevent complement-mediated lysis and activation of endothelial cells
      that leads to hyperacute rejection.

PMID- 7515199
TI  - Excitatory amino acid-induced excitation of dopamine-containing neurons in the
      rat substantia nigra: modulation by kynurenic acid.
AB  - Kynurenic acid (KYNA), an endogenous antagonist of ionotropic excitatory amino
      acid (EAA) receptors, was tested for its ability to modulate N-methyl-D-aspartate
      (NMDA)- and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      induced excitation of dopamine (DA)-containing neurons in the zona compacta of
      the rat substantia nigra (SNc). Experiments were conducted using extracellular
      recording techniques in conjunction with an in vitro brain slice preparation.
      Bath application of NMDA (1-20 microM) or AMPA (0.5-10 microM) produced a
      concentration-dependent increase in the firing rate of SNc DA neurons but had no
      effect on firing pattern. The highest concentration of both agonists produced a
      rapid and reversible cessation of activity that was attributed to acute induction
      of depolarization block. Addition of glycine (GLY) (up to 100 microM) to the
      bathing solution had no effect on either basal firing rate or the increase in
      activity produced by NMDA. KYNA (10 microM-1 mM) antagonized the excitatory
      effects of both NMDA (15 microM) and AMPA (3 microM) in a concentration-dependent
      fashion (IC50:102 microM and 64 microM, respectively) without affecting basal
      firing rate. Perfusion of tissue slices with a modified Ringer's solution
      containing low Mg2+ (0.12 mM) increased NMDA-induced excitation but did not
      affect the antagonist properties of KYNA. D-serine (100 microM) reversed the
      ability of KYNA to block the excitatory effects of NMDA, suggesting that KYNA
      attenuates NMDA-induced excitation of SNc DA neurons via blockade of the GLY
      allosteric site on the NMDA receptor. The ability of KYNA to modulate the
      excitatory effects of both NMDA and non-NMDA agonists implies that endogenous
      KYNA may play a physiological role in regulating DA cell excitability.

PMID- 7515202
TI  - Molecular staging of prostate cancer with the use of an enhanced reverse
      transcriptase-PCR assay.
AB  - OBJECTIVE: Because up to 40 percent of surgically treated patients with prostate
      cancer are subsequently found to be clinically understaged, a more sensitive
      staging modality to identify extraprostatic disease prior to surgery is required.
      METHODS: We describe an enhanced reverse transcriptase [RT] polymerase chain
      reaction (PCR) assay utilizing oligonucleotide primers specific for the human
      prostate-specific antigen (PSA). This assay identifies PSA-synthesizing cells
      from reverse transcribed mRNA. This assay was applied to RNAs extracted from the
      peripheral blood lymphocytes of 65 patients with clinically localized prostate
      cancer. In addition, blood from 20 women, 20 young men, 25 age-matched control
      men under treatment for benign prostatic hyperplasia (BPH), and 18 men with
      established, untreated metastatic prostate cancer was tested. RESULTS: An RT-PCR
      assay for PSA can recognize one PSA-expressing cell diluted into one hundred
      thousand lymphocytes. The sensitivity of this assay can be enhanced by the
      addition of digoxigenin-modified nucleotides to the PCR reaction and this assay
      was applied to RNAs extracted from the peripheral lymphocyte fraction of 148
      prostate cancer patients and controls at this institution. Although no specimen
      from women or men without cancer was positive in this assay, 14 of 18 metastatic
      prostate cancer patients were positive (77.8%). Additionally, 25 of 65 (38.5%)
      patients with clinically localized disease (T1-2b) were positive from blood
      specimens obtained prior to surgery. Final pathologic results from this group of
      patients identified a correlation between positivity on this assay and the
      presence of capsular tumor penetration (sensitivity, 68%; specificity, 84%) as
      well as strong correlation with the finding of carcinoma at the surgical margin
      (sensitivity, 87%; specificity, 76%). Logarithmic regression analysis of the
      results of the RT-PCR assay indicates its remarkable superiority to digital
      rectal examination, computed tomography scan, endorectal coil magnetic resonance
      imaging, PSA, prostate-specific antigen density, or Gleason score for predicting
      the true pathologic stage of prostate cancer in these surgically treated
      patients. CONCLUSIONS: An RT-PCR assay using PSA primers to detect prostate cells
      in the peripheral circulation of surgical-candidate patients is significantly
      correlated with capsular penetration and tumor-positive surgical margins. This
      molecular assay provides a sensitive and specific means to stage correctly
      apparent localized prostate cancer prior to radical prostatectomy.

PMID- 7515205
TI  - Transurethral evaporation of prostate (TUEP) with Nd:YAG laser using a contact
      free beam technique: results in 61 patients with benign prostatic hyperplasia.
AB  - OBJECTIVE: This prospective study was undertaken to evaluate the safety and
      efficacy of neodymium:yttrium-aluminium-garnet (Nd:YAG) laser for treatment of
      symptomatic benign prostatic hyperplasia (BPH). METHODS: A total of 61 patients
      at a mean age of 71.6 years with symptomatic bladder outlet obstruction due to
      BPH underwent transurethral evaporation of prostate (TUEP) using Nd:YAG laser.
      Twelve of the patients were experiencing acute retention. Pre- and postoperative
      evaluation consisted of American Urological Association (AUA) symptom
      questionnaire and a sexual function questionnaire, uroflowmetry, postvoid
      residual urine, electrolytes, blood urea nitrogen, creatinine, hematocrit, and
      prostate volume estimation by transrectal ultrasound. TUEP was achieved by
      employing a side-firing Nd:YAG laser fiber with a durable quartz reflector and
      high-power density (Ultraline, Heraeus LaserSonics, Milpitas, CA) that was used
      in a contact mode. RESULTS: All patients have been evaluated for three months, 26
      for six months, and 7 for twelve months. Mean prostatic size was 41.1 g. The mean
      improvement in symptom scores at one, three, six, and twelve months was 69.8
      percent, 70.9 percent, 76.0 percent, and 70.9 percent, respectively (P = <
      0.0001). The mean increase in maximum uroflow at one, three, six, and twelve
      months was 63.4 percent, 66.7 percent, 41.94 percent, and 164.52 percent,
      respectively (P = < 0.0001). There was no instance of significant fluid
      absorption or bleeding. The duration of postoperative catheterization was two
      days in 43 patients, three to seven days in 16 patients, and two to three weeks
      in 2 patients. There were no deaths. All patients evaluated by TRUS at six months
      had open channeling defects. Videocystoscopy performed in 16 patients at two to
      three months postoperatively revealed tissue slough. At repeat cystoscopy in
      these patients at six months, the prostatic fossa was completely healed with no
      evidence of tissue slough. CONCLUSIONS: It is concluded that the technique of
      TUEP using Nd:YAG laser is safe and, in preliminary results, appears apparently
      effective in the management of BPH.

PMID- 7515204
TI  - Transurethral ultrasound-guided laser-induced prostatectomy (TULIP) for benign
      prostatic hyperplasia: clinical utility at one-year follow-up and imaging
      analysis.
AB  - OBJECTIVE: The clinical utility of transurethral ultrasound-guided laser-induced
      prostatectomy (TULIP) for benign prostatic hyperplasia (BPH) and the laser effect
      on prostatic tissue were investigated. METHODS: TULIP was carried out under
      epidural anesthesia on 30 patients with symptomatic BPH (aged 63-92 years; mean,
      73.9 years). RESULTS: Excluding 4 cases that were lost to follow-up, the mean
      modified Boyarsky symptom score significantly improved (P < 0.001) from a
      preoperative level of 22.2 +/- 5.3 to 7.7 +/- 4.3 at three months and 6.2 +/- 4.1
      at one year. Maximum flow rate increased from 7.9 +/- 3.4 mL/sec to 14.5 +/- 5.9
      mL/sec at three months and 14.7 +/- 6.3 mL/sec at one year (P < 0.001). A
      decrease in residual urine volume from 72 +/- 65 mL to 10 +/- 18 mL at three
      months and 16 +/- 17 mL at one year was also noted (P < 0.005). Transrectal
      ultrasonography revealed that estimated prostate volume was decreased from 39.7
      +/- 20.4 mL to 26.9 +/- 20.3 mL at three months (P < 0.05) but it regrew to 32.2
      +/- 26.2 mL at one year. Magnetic resonance imaging clearly showed less enhanced
      area to a depth of approximately 10 mm in the periurethral region, which could be
      attributable to coagulation necrosis in the prostatic tissue. Adverse effects
      were limited to epididymitis in 2 cases and no sexual dysfunction was associated
      with the procedure. CONCLUSIONS: TULIP is an effective and safe alternative
      procedure to induce long-lasting relief of prostatic obstruction by coagulation
      necrosis in the periurethral region.

PMID- 7515203
TI  - Cigarette smoking and prostatism: a biphasic association?
AB  - OBJECTIVE: To evaluate the association between cigarette smoking and prostatism
      in a community-based setting using standardized urinary symptom scores, peak
      urinary flow rates, and prostatic volume as indicators of disease. METHODS: A
      population-based cohort of 2,115 Caucasian men aged forty to seventy-nine years
      from Olmsted County, Minnesota, was administered a previously validated
      questionnaire that elicited information on frequency of urinary symptoms
      (approximating the American Urological Association's symptom index), and a
      detailed history on cigarette smoking, including both amount and pack-years of
      smoking. Peak urinary flow rates were measured by a standard uroflowmeter (Dantec
      1000). The prostatic volume was measured for a subsample of 471 men by
      transrectal ultrasound. RESULTS: Compared to never-smokers, smokers were less
      likely to have moderate to severe urinary symptoms (age-adjusted odds ratio 0.82;
      95% confidence interval [CI] 0.61 to 1.08). This varied by smoking intensity,
      however; in men who smoked less than 1 pack a day the age-adjusted odds ratio was
      0.53 (95% CI 0.33 to 0.83) and among men smoking 1 to 1.4 packs a day, the odds
      ratio was 0.87 (95% CI 0.56 to 1.36). For men who smoked 1.5 packs or more a day,
      the odds ratio was elevated at 1.32 (95% CI 0.84 to 2.07). Smokers were less
      likely to have peak flow rates less than 15 mL/sec compared with never-smokers
      (age- and voided volume-adjusted odds ratio 0.48; 95% CI 0.35 to 0.66), or
      prostatic volume greater than 40 mL (odds ratio 0.54; 95% CI 0.19 to 1.55).
      CONCLUSIONS: These data from a community-based sample suggest that light or
      moderate smokers are less likely to have moderate to severe prostatism, whereas
      heavy smokers are at least as likely to have moderate to severe prostatism
      compared with never-smokers.

PMID- 7515206
TI  - Radical prostatectomy for adenocarcinoma of the prostate: the influence of
      preoperative and pathologic findings on biochemical disease-free outcome.
AB  - OBJECTIVE: This retrospective study evaluated the outcome for a cohort of men
      undergoing radical retropubic prostatectomy alone as primary treatment for
      clinical T1-2 prostate adenocarcinoma. METHODS: Sixty-two patients treated at
      Boston University Medical Center between 1987 and 1992 underwent radical
      prostatectomy alone without adjuvant or neoadjuvant endocrine therapy. Actuarial
      and multivariate analyses were made of disease-free outcome according to
      preoperative tumor T stage, prostate-specific antigen (PSA), and biopsy grade,
      and according to the pathologic findings at surgery. Recurrence was defined as
      the persistence or recurrence of detectable serum PSA four or more weeks
      following surgery. RESULTS: Of all patients judged clinically to have localized
      disease (T1-2), 52 percent proved to have pathologic T3 tumors. Of these, 81
      percent had positive surgical margins. The strongest preoperative predictors of
      pT3 disease were the biopsy Gleason grade and the initial serum PSA value.
      Actuarial analysis showed the overall likelihood of remaining free from
      detectable PSA at four years to be 43 percent (75% for those with organ-confined
      disease and 27% for those who were pT3). The poorest prognosis was seen in those
      with seminal vesicle involvement. Biopsy Gleason grade and initial PSA were
      independent preoperative predictors of biochemical failure in a Cox regression
      analysis but clinical T stage was not. CONCLUSIONS: The biopsy Gleason grade and
      initial PSA were identified as strong preoperative predictors of disease-free
      outcome. We confirmed the favorable prognosis of men with organ-confined disease,
      but emphasize the high likelihood of relapse in those with positive surgical
      margins or seminal vesicle invasion.

PMID- 7515201
TI  - Fluconazole therapy in transplant recipients receiving FK506.

PMID- 7515207
TI  - Review of the role of androgenic hormones in the epidemiology of benign prostatic
      hyperplasia and prostate cancer.
AB  - OBJECTIVE: Examine current knowledge and concepts on the role of androgenic
      hormones in the epidemiology of benign prostatic hyperplasia (BPH) and prostate
      cancer (PCa). METHODS: Review of the clinical and scientific literature on normal
      androgen physiology, hormonal physiology of BPH and PCa tissue, serum hormone
      levels in patients with BPH or PCa, and the correlation between serum and tissue
      androgenic hormones. RESULTS: BPH and PCa are enormous clinical problems for our
      health care system; profound changes in the clinical aspects of these diseases
      are evident in recent years. Early identification or prevention are realistic
      goals; identification of higher risk groups would be extremely valuable. Androgen
      stimulation of the prostate is likely to be important in the promotion of BPH or
      PCa. Tissue hormone measurements have not identified substantial differences in
      hormone levels, but precise pathologic control of the tissue examined is suspect.
      Examinations of serum hormone levels in disease states have produced conflicting
      results, but the presence or absence of BPH or PCa was often based on imprecise
      clinical observations, making interpretation difficult. There are minimal data
      confirming that the serum hormones measured previously actually reflect
      intraprostatic tissue activity. CONCLUSIONS: The value of serum hormone
      measurements to identify higher risk groups for BPH or PCa is an area of
      continuing uncertainty because of substantial flaws in the design of many
      previous studies based on a failure both to define the presence or absence of BPH
      or PCa precisely in patients studied and measure the appropriate androgen
      metabolites. Similarly, it is not possible reliably to implicate differences in
      androgenic stimulation as a cause for racial differences in PCa. The ability of
      serum hormone levels to correlate with prostatic tissue androgenic stimulation
      has not been evaluated. Additional research in the relationships between
      androgenic stimulation and the development of clinically significant BPH or PCa
      is needed.

PMID- 7515211
TI  - Management of hormone resistant prostate cancer.
AB  - No systemic therapy has led to prolongation of life in patients with hormone
      resistant prostate cancer though secondary hormone treatment and chemotherapy
      have resulted in an about 30% response rate. The main goal of treatment is
      palliation and improvement of quality of life, the former aim obtained in 50-70%
      of the patients by radiotherapy of skeletal metastases. The evaluation of
      response, today assisted by the use of prostate specific antigen, and the
      understanding of hormone resistance remain principal topics of clinical research
      in hormone resistant prostate cancer.

PMID- 7515208
TI  - Dermal toxicity of hexachlorocyclohexane and pirimiphos-methyl in female rats.
AB  - Technical hexachlorocyclohexane (100 mg/kg/d) and pirimiphosmethyl EC 50 (250
      mg/kg/d) given individually and in combination to female rats for 7, 15 or 30 d
      by skin application caused poisoning, pathomorphological changes in vital organs,
      and significant enzymatic changes in liver and serum. The changes produced by the
      2 compounds in combination did not suggest potentiation at the tested dose
      levels.

PMID- 7515210
TI  - [Symptoms, self concept and developmental delay in healthy and chronically ill
      adolescents with type I diabetes].
AB  - In a prospective four-year longitudinal study 108 adolescents with diabetes and
      107 healthy adolescents are being compared. In this paper data are presented from
      the initial assessment, in which psychopathology in the two groups was compared.
      In addition, the effect of diabetes on psychosocial development was examined.
      Several questionnaires were administered to assess symptomatology, self-concept
      and progress on certain developmental tasks. Regarding symptomatology, diabetic
      youths described themselves as more normal, i.e. having fewer clinical symptoms,
      than did the healthy controls. In addition, they had remarkably high scores on a
      scale of social desirability. This latter result points to a defence mechanism.
      Only the group of males with poorly controlled diabetes openly acknowledged that
      they had problems. All of the diabetics showed clear delays in psychosocial
      development compared with their healthy agemates. There were significant delays
      in developmental areas involving achievement of autonomy from parents and
      orientation towards member of one's own age group (regardless of sex), and the
      subjects with diabetes put less emphasis than the healthy controls on the
      importance of being successful in these areas in the future.

PMID- 7515212
TI  - Octreotide in advanced prostatic cancer relapsing under hormonal treatment.
AB  - Since somatostatin analogues have been shown to possess inhibitory activity on
      prostatic cancer cells in animal models, we studied the clinical effects of the
      long-acting somatostatin analogue octreotide in the treatment of advanced
      prostatic cancer. Five patients with metastatic prostatic cancer in relapse under
      hormonal treatment and with rapidly increasing levels of prostate specific
      antigen (PSA) received a subcutaneous infusion of octreotide in a dose of 400 to
      1,000 micrograms/day for a period of 2 to 6 months. Patients were followed
      clinically and by monthly measurement of PSA levels. During treatment 3/5
      patients showed a temporary halt in rising PSA levels, while another patient had
      a small decrease. This inhibitory effect however was lost after 1 to 3 months of
      therapy in 3 patients. The remaining patient died after 4 months before an escape
      of PSA levels was seen. Side effects consisted of mild diarrhoea in three
      patients. From this very preliminary data, it appears that octreotide in a dose
      of 400 to 1,000 micrograms/day may give only a moderate and temporary inhibition
      of tumor growth in patients with advanced prostatic cancer. Because of the
      limited effects the study was interrupted prematurely. Since higher doses, other
      somatostatin-analogues or the combination of LHRH analogues may give better
      results, further studies are needed to determine the potential therapeutic role
      of somatostatin-analogues in this group of patients.

PMID- 7515209
TI  - [Reliability and validity of the German version of the Youth Self Report].
AB  - The aim of the present study was to investigate certain aspects of the
      reliability and validity of a German version of the Youth Self-Report (total
      behavior problem score) and to establish norms. In a sample of 252 patients from
      various child and adolescent psychiatric services and in an unselected sample of
      1343 students from nearby schools high coefficients of internal consistency and
      split-half reliability (> 0.9) were obtained. An additional 105 students were
      tested and then retested after 5 weeks and again the rank correlations were high
      (boys: 0.86; girls: 0.90). The patients had higher total problem scores than the
      non-patients matched for age, sex, socioeconomic status, type of school and
      status as a foreigner. Patients with a diagnosis on axis 1 (psychiatric syndrome)
      or axis 5 (abnormal psychosocial situations) of the Multi-axial Classification
      Scheme were more maladjusted (higher total behavior problem score) than those
      without such a diagnosis. As expected, the score for the inpatients (N = 99) was
      higher than for the outpatients (N = 153). Because of the encouraging results,
      which justify further use of the Youth Self-Report, norms for the total behavior
      problem score (T-scores, percentiles) were calculated separately for the boys (N
      = 2085) and girls (N = 2119) from the general population (10-17 years of age).

PMID- 7515213
TI  - Usefulness of intermittent monitoring of mixed venous oxygen saturation after
      stage I palliation for hypoplastic left heart syndrome.
AB  - Most deaths after stage I palliation for hypoplastic left heart syndrome have
      occurred within the first 24 hours after surgery. Efforts to improve 1-day
      survival should therefore have significant impact on improving overall survival.
      Early death has most often been attributed to low cardiac output and
      abnormalities of pulmonary to systemic flow ratio (Qp/Qs). Thirteen infants
      underwent stage I palliation and had a catheter inserted in the high superior
      vena cava (SVC) for intermittent measurement of SVC oxygen saturation.
      Calculation of Qp/Qs was achieved using SVC saturation as a mixed venous oxygen
      saturation, and estimating pulmonary venous oxygen saturation. Eleven patients
      survived, and 2 patients died within the first 24 hours. Abnormalities in Qp/Qs
      were noted in 12 of 13 patients after operation. In 10 of these 12 patients,
      there was a high Qp/Qs, which has been associated with poor outcome. High Qp/Qs
      was noted even in patients with acceptable arterial oxygen saturations (< 85%).
      SVC saturation increased in all survivors during the first 24 hours, and was
      associated with a decrease in Qp/Qs. Measurement of SVC oxygen saturation appears
      to be a valuable adjuvant in the postoperative management of infants after stage
      I palliation of hypoplastic left heart syndrome. Major abnormalities in Qp/Qs can
      be detected even with acceptable arterial saturations. With this information,
      early ventilator/pharmaceutical adjustments can be made which may improve stage I
      survival.

PMID- 7515214
TI  - Fine T-cell subsets in alcoholics as determined by the expression of L-selectin,
      leukocyte common antigen, and beta-integrin.
AB  - Alcoholics admitted to the hospital solely for detoxication have been studied by
      flow cytometry to evaluate changes in the surface markers of peripheral blood
      leukocytes. As we have shown previously, such patients have an elevated
      percentage of CD8hi lymphocytes that are HLA DR+; we now demonstrate that they
      also have striking alterations in the quantitative relationships of the fine T
      cell subsets. Both CD4+ and CD8hi lymphocytes have a sharply reduced percentage
      of the L-selectin+ CD45RA+ subset, increased percentages of the CD45RA- subsets,
      and several other fine subset alterations. The fine subset profile suggests,
      according to current correlations of phenotype and function, that both CD4+
      suppressor inducer and CD4-dependent CD8+ suppressor effector cells are reduced,
      whereas other subsets, including CD8+ CTL or their precursors, are increased in
      relative percentages. Some of the phenotypic changes are reversible over the
      several days following withdrawal. In other results, the percentage of CD8hi
      lymphocytes epxressing CD11b (beta-integrin) is shown to be reciprocal with the
      percentage expressing L-selectin both in normals and alcoholics. However, the
      regression function of CD11b vs. L-selectin on CD8hi cells is different for the
      alcoholics than for the normals, indicating an abnormality in the regulation of
      the expression of these two adhesion markers. Taken together, this abnormality of
      adhesion molecules and the fine subset alterations previously described indicate
      widespread changes in the peripheral lymphocytes of currently drinking
      alcoholics. These changes suggest functional deficiencies that may include
      alterations of lymphocyte traffic and other adhesion-dependent functions, and a
      shift in the balance of regulatory interactions.

PMID- 7515215
TI  - Adhesion molecules of allergic inflammation: recent insights into their
      functional roles.

PMID- 7515216
TI  - Nitric oxide synthase inhibitor does not reduce minimum alveolar anesthetic
      concentration of halothane in rats.
AB  - Nitric oxide (NO) synthase inhibitor (N omega-nitro-L-arginine methyl ester [L
      NAME]) has been reported to reduce minimum alveolar anesthetic concentration
      (MAC) of halothane when administered intravenously (i.v.) and to reduce thermal
      hyperalgesia, or produce antinociception in the formalin test, when administered
      intracerebroventricularly (ICV) or intrathecally (IT). This study attempts to
      identify the site(s) in the central nervous system (CNS) where L-NAME acts to
      reduce the halothane MAC. For this purpose, we examined the effects of i.v., ICV,
      and IT administration of L-NAME on the halothane MAC in rats. In contrast to an
      earlier study, we did not observe any decrease in the halothane MAC after i.v.
      (10-30 mg/kg) administration of L-NAME. ICV (100 micrograms) and IT (100
      micrograms and 1 mg) administration of L-NAME also did not alter the halothane
      MAC. These findings indicate that the L-arginine-NO pathway is not involved in
      the mechanism of action of halothane to suppress mechanical nociceptive response
      or in the nociceptive neural mechanism of mechanical stimulation.

PMID- 7515218
TI  - Treatment of ventricular arrhythmias after recovery from myocardial infarction.
AB  - Demonstrated associations between postmyocardial infarction ventricular
      arrhythmias and a higher subsequent risk of both sudden and all-cause mortality
      have prompted a search for effective and safe treatment modalities. Recently
      completed clinical trials have provided a rationale for treatment recommendations
      in some specific settings. Beta-blocking therapy is recommended for
      postinfarction patients with frequent or complex ventricular premature beats. In
      contrast, calcium antagonist therapy is not helpful in these cases, and Class I
      antiarrhythmic therapy is actually harmful. Early indications of benefit from
      Class III antiarrhythmic therapies, particularly amiodarone, are under evaluation
      in large trials. Patients with sustained ventricular tachycardia (VT) or
      ventricular fibrillation (VF) occurring late after myocardial infarction require
      therapy. Viable therapeutic methods include individualized antiarrhythmic therapy
      selected by the noninvasive approach, individualized antiarrhythmic therapy
      selected by the invasive approach, empiric amiodarone therapy, transcatheter or
      surgical ablative therapy (for VT), and use of an implantable cardioverter
      defibrillator. Clinical trial data have yet to determine which of these
      approaches is most effective under which circumstances. Postinfarction patients
      with nonsustained VT are the focus of several ongoing treatment trials. Early
      data suggest that risks requiring specific therapy are reached only by those
      patients who also have significant left ventricular dysfunction. The presence of
      inducible sustained ventricular tachycardia at an electrophysiologic study may
      further risk stratify such patients. High-risk patients with nonsustained
      ventricular tachycardia, left ventricular dysfunction, and inducible sustained
      ventricular tachycardia should participate in ongoing clinical trials. In the
      absence of this opportunity, intensive treatment should be considered.

PMID- 7515217
TI  - Acute zinc chloride ingestion in a child: local and systemic effects.
AB  - A 16-month-old boy ingested liquid zinc chloride/ammonium chloride soldering
      flux. He developed severe local burns, metabolic acidosis, hepatic damage,
      hyperamylasemia, lethargy, and hypertension. Peak measured plasma zinc was 1,199
      micrograms/dL. Because of persistent signs of systemic toxicity, he was chelated
      with dimercaprol (BAL) and EDTA. Although clinical improvement was noted
      coincident with the initiation of chelation, there was no apparent increase in
      urinary zinc excretion. Scarring in the gastric antrum necessitated an
      antrectomy. The child recovered without other apparent complications.

PMID- 7515219
TI  - Prostate carcinoma.
AB  - Over the last several years, the development of prostate-specific antigen (PSA)
      testing and technical refinements of anatomic radical prostatectomy have
      revolutionized the care of patients with prostate cancer. Serum PSA testing often
      allows early diagnosis of organ-confined prostate cancer. Anatomical radical
      prostatectomy has a high probability of completely eradicating these tumors, with
      minimal long-term morbidity. Use of PSA testing after therapy confirms the long
      term ability of surgery to eradicate early-stage prostate cancer.

PMID- 7515220
TI  - Endothelial-leukocyte adhesion molecules in human disease.
AB  - An effective host response to infection or tissue damage requires focal
      accumulation of leukocytes. Leukocyte adhesion to the vessel wall, a key step in
      this process, depends on the ordered expression of specific endothelial cell
      surface molecules. The endothelial molecules that support adhesion include
      selectins that recognize leukocyte cell surface glycoconjugates as well as
      members of the immunoglobulin superfamily that interact with leukocyte integrins.
      Although inflammation can occur with minimal damage to the vessel wall and
      surrounding tissues, control mechanisms sometimes appear to fail, and the
      inflammatory response itself becomes a significant clinical problem. In this
      review, we discuss endothelial-leukocyte adhesion molecules with particular
      emphasis on their expression and function in human disease. Pathophysiological
      processes presented include atherosclerosis, ischemia-reperfusion injury, acute
      lung injury, rheumatoid arthritis, and graft rejection. A more detailed
      description of the discovery and characterization of the key molecules appears in
      the antecedent article entitled "Endothelial-Leukocyte Adhesion Molecules".

PMID- 7515222
TI  - Biological and clinical aspects of hematopoietic stem cells.
AB  - Recent advances in cell isolation techniques have greatly enhanced our
      understanding of the phenotype and function of hematopoietic stem cells in mice
      and humans. Many clinical studies have established the efficacy of using
      peripheral blood stem cells to supplement or replace bone marrow transplantation
      as a therapeutic modality for several types of malignancies. This new approach to
      malignant disease management, perhaps in combination with posttransplantation
      cytokine therapy, promises to completely alter the clinical course of bone marrow
      transplantation.

PMID- 7515221
TI  - Intestinal transplantation.
AB  - Intestinal transplantation is often the only alternative form of treatment for
      patients dependent on total parenteral nutrition for survival. Although a limited
      number of intestinal transplantations have been performed, results with FK 506
      immunosuppression are comparable to those for other organ transplants. The impact
      of successful intestinal transplantation on gastroenterology will likely be
      similar to the impact of kidney and liver transplantation on nephrology and
      hepatology.

PMID- 7515224
TI  - Inhibition of in vitro reconstitution of rotavirus transcriptionally active
      particles by anti-VP6 monoclonal antibodies.
AB  - Six monoclonal antibodies specific for the major capsid protein of rotavirus,
      VP6, previously characterized, were tested in a biological assay for their
      capacity to block the transcriptase activity associated with the single-shelled
      particles. The results showed that two MAbs (RV-50 and RV-133), specific for
      distinct antigenic sites, were able to block the transcription when they were
      incubated with a purified baculovirus-expressed group A VP6, prior to the
      reconstitution of the single-shelled particles from the cores, suggesting that at
      least two domains are involved in active single-shelled particle reconstitution.
      The results obtained previously from immunochemistry of synthetic peptides did
      not allow us to attribute this biological activity to a particular linear
      sequence of the protein, the domain involved being probably complex and dependent
      on the folding of the protein. However, the C-terminal end, which is necessary
      for binding into single-shelled particles could be necessary but not sufficient
      to restore the transcription, since neither of these two MAbs reacted
      significantly with peptides of this region. These two MAbs will be useful
      reagents to study the interactions between VP6 and the cores.

PMID- 7515223
TI  - Human cytomegalovirus replication correlates with differentiation in a
      hematopoietic progenitor cell line and can be modulated by HIV-1.
AB  - Human cytomegalovirus (HCMV) infection of a CD34+ hematopoietic progenitor cell
      line (TF1) was studied before and after TPA differentiation. TF1 cells were found
      to be infected but the virus does not replicate, while differentiated TF1 cells
      can be infected and allow HCMV complete replication. In the same system we
      studied the interaction between HCMV and HIV and found that while contact between
      HIV gp 120 and the HCMV-infected cell has an inhibitory effect, exogenous Tat
      protein stimulates HCMV replication. The interaction between HCMV and HIV in
      hematopoietic progenitor cells is complex and depends on several factors that can
      have opposite effects.

PMID- 7515225
TI  - Replication of influenza B virus in chicken embryos is suppressed by exogenous
      aprotinin.
AB  - Chicken embryo proteinases, one of which is a blood clotting factor Xa-like
      proteinase, are known to effectively cleave the haemagglutinin (HA) of Influenza
      B viruses to permit their replication in chicken embryonated eggs. Here we show
      that injection of the serine proteinase inhibitor, aprotinin, into the allantoic
      cavity of eggs infected with Influenza B/Hong Kong/73 and B/Lee/40 viruses
      suppresses the viral HA cleavage and reduces the virus proteolytic activation and
      replication. Effective inhibition dose was determined as approximately 10.0
      micrograms of aprotinin per embryo that corresponds to 0.1 microM concentration.
      However, heparin, which is known to be a direct inhibitor of the Factor Xa, was
      not able to suppress Influenza B virus hemagglutinin cleavage and replication in
      chicken embryo system. These data shed light on the pattern of proteinases
      involved in the Influenza B virus proteolytic activation and indicate that
      aprotinin possesses antiviral potential against Influenza B viruses.

PMID- 7515229
TI  - Effect of storage of smears on the staining of ram spermatozoa by eosin or trypan
      blue.

PMID- 7515227
TI  - Histamine release from rabbit platelets by platelet-activating factor (PAF).
AB  - In this study, we examined firstly whether PAF could activate washed platelets of
      rabbits and release ATP from the platelets, secondly whether activated platelets
      could release histamine, and thirdly whether certain antagonists of PAF could
      inhibit the release of histamine from platelets. The results obtained in these
      experiments may be summarized as follows. 1) Release of ATP was increased with
      enhanced platelet aggregation by PAF. At 3.4 x 10(-7) M of PAF, the maximal
      aggregation rate of platelets was about 70% and the concentration of released ATP
      was 1.6 x 10(-5) M. 2) After aggregated platelets induced by PAF had been
      sonicated and centrifuged, the resultant supernatant could cause contraction of
      the guinea pig ileum. This contraction was inhibited by the antihistaminic
      agents, cimetidine and pyrilamine. Furthermore, the histamine content of the
      supernatant was about 3.7 micrograms/ml (platelet count, 30 x 10(4)/microliter).
      3) At 10(-5) M of CV-3988, the inhibitory ratio of PAF-induced aggregation was
      35% and that of histamine release was 50%. On the other hand, at 5 x 10(-7) M of
      CV-6209, the inhibitory ratio of PAF-induced aggregation was 35% and that of
      histamine release was about 30%. From the above results, it was clear that PAF
      activated platelets could release histamine. In addition, it is suggested that a
      direct relationship between PAF and platelets may exist in the process of
      allergic reactions, and histamine from PAF-activated platelets may modify
      allergic reactions.

PMID- 7515226
TI  - Comparison of the polymerase region of small round structured virus strains
      previously classified in three antigenic types by solid-phase immune electron
      microscopy.
AB  - We have used a reverse transcription-polymerase chain reaction with nested sets
      of primers to determine the nucleotide sequences of a 166 base pair segment of
      the RNA polymerase region of seven strains of small round structured viruses
      (SRSVs) from the United Kingdom. These SRSV strains were previously classified by
      solid-phase immune electron microscopy into three antigenic types--UK2, UK3 and
      UK4, which are comparable to the prototype strains Norwalk virus, Hawaii agent,
      and Snow Mountain agents, respectively. Based on their sequences, the seven
      strains from the United Kingdom could be divided into two groups. The first group
      included two strains of the UK2 type along with Norwalk virus and Southampton
      virus and the second group included three strains of UK3 and two strains of UK4
      types. Viruses in the first group showed 75.3%-77.1% nucleotide and 89.1%-94.6%
      amino acid identity with Norwalk virus while those of the second group showed
      60.8%-63.3% nucleotide and 67.3%-69.1% amino acid identity. Nucleotide and amino
      acid identity within the second group ranged between 91.6%-99.4% and 96.4%-100%,
      respectively. These results suggest that the SRSVs antigenically related with
      Norwalk virus, Hawaii agent, and Snow Mountain agent, can be classified into two
      genotypes on the basis of their sequences in the RNA polymerase region.

PMID- 7515230
TI  - Endogenous nitric oxide modulates endothelin-1 induced contraction of bovine
      oviduct.
AB  - We recently reported that oviduct epithelial cells in culture produce endothelin
      (ET) and postulated that ET could play an important role in the contraction of
      the oviduct. In the present study using an organ chamber myograph system, we
      evaluated the contractile effects of ET-1 on bovine oviduct ampullary-isthmus
      segments. Additionally, the possibility whether the basal release/synthesis of
      nitric-oxide (N(O)) and/or prostacyclin modulates the contractile effect of ET-1
      was investigated. ET-1 (10(-10) to 10(-7) M) contracted oviduct rings in a
      concentration dependent manner (P < 0.05). ET-1 (10(-7) M) induced contractions
      were significantly enhanced in presence of nitric oxide synthase inhibitor N
      nitro-L-arginine-methyl-ester (10(-4) M), but remained unaltered in the presence
      of indomethacin (10(-5) M), an inhibitor for prostacyclin synthesis. In
      conclusion, ET-1 induced contraction of the oviduct is reduced/modulated by
      endogenous basal release/synthesis of N(O).

PMID- 7515231
TI  - Secondary structure of noxiustoxin and charybdotoxin from hydropathy power
      spectra.
AB  - The analysis of the hydropathy profile power spectra provides a basis for studies
      of pattern matching between the primary and secondary structure of peptides. The
      structural motif obtained with Noxiustoxin (NTX), the first K+ channel blocking
      peptide described, is composed of a N-terminal beta-strand, a central alpha-helix
      and a final beta-strand zone, probably forming a beta-sheet. These results were
      compared with those of Charybdotoxin (ChTX), a potent inhibitor of the high
      conductance Ca(2+)-activated K+ channel, which presents about 48% similarity with
      NTX in the amino acid sequence. Our prediction for ChTX secondary structure,
      which is known by 2D-NMR spectroscopy, yielded a Chou-Fasman quality index Q =
      90%. The comparison between the two toxins has guided the interpretation of the
      data obtained.

PMID- 7515232
TI  - Rat contrapsins are the type II acute phase proteins: regulation by interleukin 6
      on the mRNA level.
AB  - Three highly homologous serine protease inhibitors, SPI-1, SPI-2 and SPI-3
      (contrapsins), are synthesized in rat liver. Their expression is regulated
      differently in healthy and inflamed animals. We found that interleukin 6 (IL-6),
      a major acute phase cytokine, and to a lesser extent leukemia inhibitory factor
      (LIF), both together with glucocorticoids, are responsible for the regulation of
      expression of the contrapsins in rat hepatocytes in primary culture. The effect
      of IL-6 is time- and dose-dependent. IL-1, TGF beta 1, HGF, PMA and IL-8 did not
      have any effect on contrapsin mRNA levels. We postulate that SPI-1, SPI-2 and SPI
      3 belong to the class II acute phase proteins. Additionally, we show induction of
      SPI-3 mRNA in rat liver by in situ hybridization using a specific oligonucleotide
      probe.

PMID- 7515233
TI  - In human neutrophils the binding to immunocomplexes induces the tyrosine
      phosphorylation of Fc gamma RII but this phosphorylation is not an essential
      signal for Fc-mediated phagocytosis.
AB  - It has been recently suggested that protein tyrosine phosphorylation is involved
      in Fc gamma Rs-mediated signalling. In this paper we have investigated if in
      human neutrophils a tyrosine phosphorylation of Fc gamma RII takes places after
      the binding with immunocomplexes and if this phosphorylation plays a role in
      phagocytic signal. The immunoprecipitation with mAb anti-Fc gamma RII of lysates
      of neutrophils challenged in suspension with insoluble immunocomplexes (IIC) or
      sheep erythrocytes opsonized with IgG (E-IgG), followed by immunoblotting with
      anti-phosphotyrosine antibody, demonstrated that Fc gamma RII was tyrosine
      phosphorylated. When neutrophils were pretreated with different doses of tyrosine
      kinase inhibitors, genistein or erbstatin, the phosphorylation of Fc gamma RII
      induced by IIC or E-IgG was dose dependently inhibited. In these conditions both
      genistein and erbstatin failed to inhibit the phagocytosis of E-IgG. These
      results demonstrated that in human neutrophils in suspension the binding to Fc of
      IgG induces a tyrosine phosphorylation of Fc gamma RII but this phosphorylation
      is not an essential signal for phagocytosis of IgG-opsonized particles.

PMID- 7515234
TI  - Isolation of a lipid-soluble histamine release factor from human platelets.
AB  - We have isolated a histamine release factor from human platelet supernatants by
      heparin column chromatography, gel filtration and reversed phase HPLC. Fractions
      from each chromatographic step were assayed for histamine release factor activity
      (HRF). A peak of HRF activity was detected at a molecular mass of 60 kDa.
      Subsequent HPLC purification showed that the factor co-eluted with human serum
      albumin, but was totally extractable into the lipid phase. Comparison of
      biological activity with known basophil and eosinophil-activating
      hydroxyeicosanoids demonstrated similar activity with 5(S)-hydroperoxy
      6E,8Z,11Z,14Z-eicosatetraenoic acid (5(S)-HPETE). The identification of this
      lipid soluble HRF demonstrates the novel potential role of an as yet unidentified
      lipid as an HRF, in the absence of priming stimuli.

PMID- 7515228
TI  - Serotonin and human myoclonus. Rationale for the use of serotonin receptor
      agonists and antagonists.
AB  - This is a critical review of the serotonin hypothesis of myoclonus for the
      purpose of identifying new pharmacologic therapies. The literature on myoclonus
      and serotonin neuropharmacology reveals evidence for serotonergic abnormalities
      in some human myoclonic disorders, new serotonin receptor subtypes and data on
      their molecular structure and function, more selective drugs, and experimental
      evidence linking certain serotonin receptor subtypes with myoclonus. This article
      provides an overview of clinical experience with serotonergic drugs, new
      investigational drugs, and strategies for gathering data critical to linking
      particular receptor abnormalities and drugs with specific human myoclonic
      disorders. Such information will allow the use of receptor subtype-selective
      agonists and antagonists for the treatment of myoclonus.

PMID- 7515236
TI  - [An unusual seminoma].

PMID- 7515235
TI  - A biosynthetic control on structures serving as ligands for selectins: the
      precursor structures, 3-sialyl/sulfo Gal beta 1, 3/4GlcNAc beta-0-R, which are
      high affinity substrates for alpha 1, 3/4-L-fucosyltransferases, exhibit the
      phenomenon of substrate inhibition.
AB  - The present study reports a control on the biosynthesis of fucosylated
      structures, serving as ligands for selectins by demonstrating the potential of 3
      sialyl or 3-sulfo Gal beta 1, 3/4GlcNAc beta-containing glycoconjugates as high
      affinity substrates for alpha 1, 3/4-L-fucosyltransferases and as substrate
      inhibitors at higher concentrations. The synthetic sulfated saccharides and the
      triantennary sialoglycopeptide from fetuin were potent competitive inhibitors of
      the transfer of fucose to non-anionic saccharide acceptors and the corresponding
      triantennary asialoglycopeptide respectively catalyzed by a partially purified
      alpha 1, 3/4-L-fucosyltransferase preparation from Colo 205 (specific
      activity:transfer of 113.1 nmol Fuc to 2'-FucosylLacNAc per h per mg protein); Ki
      for the inhibitions by triantennary sialoglycopeptide, 3-SulfoGal beta 1, 3GlcNAc
      beta-0-Allyl and a copolymer from 3-SulfoGal beta 1, 3GlcNAc beta-0-Allyl and
      acrylamide were 51.9 microM, 500 microM and 67.0 microM, respectively. Further,
      the alpha 1,3-specific anionic acceptor, 3'-SulfoLacNAc, also inhibited the alpha
      1,4- activity; Km for the alpha 1,4-specific acceptor, 2-methylGal beta 1,
      3GlcNAc beta-0-Bn increased from 0.40 mM to 1.35 mM in presence of 3.0 mM 3'
      sulfoLacNAc, whereas Ki for the mutual inhibition of alpha 1,3-activity by the
      former was found to be high (3.64 mM). Furthermore, the phenomenon of substrate
      inhibition, serving as acceptors at lower concentrations and as inhibitors at
      higher concentrations, was exhibited by the anionic acceptors; the Hill plots
      gave the Ki values 342.7 microM, 13.03 mM and 13.36 mM respectively for fetuin
      triantennary sialo glycopeptide, 3'-sulfoLacNAc and 3-sulfoGal beta 1, 3GlcNAc
      beta-0-Allyl.

PMID- 7515237
TI  - Aplasia cutis congenita, elevated alpha-fetoprotein, and a distinct amniotic
      fluid acetylcholinesterase electrophoretic band.
AB  - Aplasia cutis congenita affecting the elbows, knees, hips, and gluteal area was
      observed in a female newborn, product of a twin pregnancy. One of the twins was a
      fetus papyraceous detected at 15 weeks of pregnancy. During the course of the
      pregnancy, maternal thrombocytosis was diagnosed and treated with aspirin. alpha
      Fetoprotein was elevated in maternal serum and amniotic fluid, and a distinct
      electrophoretic acetylcholinesterase band was seen in amniotic fluid. These
      findings are in agreement with the classification of aplasia cutis congenita as
      proposed by Frieden et al in which type V is related to the presence of a fetus
      papyraceous or placental infarcts. The findings in the present case may be
      explained by the effect of the dead twin on the surviving fetus and the extensive
      denuded skin areas. Long-term follow-up of the infant showed that the lesions
      were cured, most of them with minimal scars. Increased risk for aplasia cutis
      congenita should be considered when elevated maternal and amniotic fluid alpha
      fetoprotein and a distinct electrophoretic band of acetylcholinesterase are
      found. Especially when one of the twins is dead.

PMID- 7515239
TI  - Early morbidity and neurodevelopmental outcome in low-birthweight infants born
      after third trimester bleeding.
AB  - Neonatal mortality, morbidity, and neurodevelopmental sequelae were compared
      between a consecutive series of 77 liveborn, low-birthweight (less than 2500 g)
      infants delivered after third trimester bleeding and 154 appropriate control
      infants of similar gestational age. Infants born after abruptio placentae had
      lower Apgar scores at 1 minute and higher rates of acidosis in comparison with
      control infants. In multivariate analysis, the infants in this group had higher
      risks of severe intraventricular hemorrhage and poor outcome (neonatal death or
      cerebral palsy) in comparison with control infants. In placenta previa, the
      infants had a higher prevalence of respiratory distress syndrome, whereas
      unclassified antepartum bleeding was associated with a high rate of neonatal
      hypoglycemia. After adjustment, by logistic regression analysis, for the effect
      of confounding factors (gestational age, birthweight, social class, and education
      of the mother), the risk of minor infant neurodevelopmental abnormalities at 2
      year follow-up was increased in infants delivered after total or partial placenta
      previa or after unclassified antepartum bleeding. Third trimester bleeding should
      be considered a strong risk factor for both short-term neonatal morbidity and
      subsequent infant neurodevelopmental impairment in the low-birthweight infant
      population.

PMID- 7515238
TI  - Perinatal prediction--a potential means for cutting public costs.

PMID- 7515240
TI  - Abnormal regional CBF response in left hemisphere of dysphasic children during a
      language task.
AB  - This study used xenon 133 inhalation and single-photon computed tomography to
      measure regional cerebral blood flow during a quiet resting condition, a simple
      auditory task, and an auditory phonemic discrimination task in 3 age-matched
      groups of children suffering from developmental language disabilities: expressive
      dysphasia, expressive-receptive dysphasia, and attention-deficit hyperactivity
      disorder. An absence of left hemisphere activation was observed in the expressive
      receptive group during the phonemic discrimination task as compared to both
      expressive and attention-deficit hyperactivity disorder children, together with
      an absence of left inferior parietal region activation in dysphasics as compared
      to hyperactive children. These results favor the hypothesis of an abnormal
      lateralization for language in dysphasic children and point toward possible
      different pathologic localizations in the different clinical subtypes of
      dysphasia.

PMID- 7515241
TI  - D-2-hydroxyglutaric aciduria in neonate with seizures and CNS dysfunction.
AB  - D-2-Hydroxyglutaric aciduria was documented in a newborn who presented with
      seizures, hypotonia, cortical blindness, a movement disorder, and developmental
      delay. Her clinical presentation differs from that of patients with L-2
      hydroxyglutaric aciduria and a single previously reported patient with D-2
      hydroxyglutaric aciduria. Cerebrospinal fluid levels of gamma-aminobutyric acid
      were elevated, while biogenic amine metabolites were normal. The movement
      disorder in our patient and in those with L-2-hydroxyglutaric aciduria suggests
      involvement of the basal ganglia in the disease process. Prenatal diagnosis of an
      affected fetus was accomplished during a subsequent pregnancy.

PMID- 7515242
TI  - Neuronal intranuclear hyaline inclusion disease with progressive cerebellar
      ataxia.
AB  - Neuronal intranuclear hyaline inclusion disease is a progressive, fatal
      neurologic condition characterized by eosinophilic inclusions in neurons of the
      central, autonomic, and peripheral nervous systems. The clinical and pathologic
      findings of a 4-year-old boy who presented with a rapidly progressive cerebellar
      ataxia and seizure disorder that had begun 2 years earlier are described.
      Although intraneuronal inclusions were identified in neurons of cortex, basal
      ganglia, brainstem, cerebellum, and spinal cord, clinical signs were restricted
      to cerebellar ataxia, internuclear ophthalmoplegia, and cognitive delay.
      Predominant cerebellar atrophy, early age of onset, and short clinical course
      distinguishes it from previously reported patients.

PMID- 7515243
TI  - A heterogeneous immune response to an SmD-like epitope by SLE patients.
AB  - Two mouse cDNA clones were isolated by immunoscreening with an SLE serum. These
      clones encode an epitope which consists of a di-peptide repeat (Gly-Arg)n (n = 9
      and 19 in isolated clones). These sequences, when expressed as fusion proteins,
      inhibit the binding of antibodies from one patient's serum to the SmD
      autoantigen. This cross-reactivity is based on the sequence identity with the
      carboxyterminal end of the human SmD [(Gly-Arg)g]. An Exonuclease III deletion
      analysis demonstrates that the minimal number of Gly-Arg repeats necessary for
      immune recognition on the Western blot is patient-specific, and varies from nine
      to three. The defined epitope is recognized by 35% of sera from patients with SLE
      as well as with other autoimmune diseases (rheumatoid arthritis, scleroderma,
      Sjogren's syndrome), in contrast to SLE-specificity of anti-Sm antibodies.
      Affinity-purified antibodies of the identified epitope cross-react with EBNA1
      protein in EBV-infected B-cell lines.

PMID- 7515245
TI  - Conceptual aspects of the thymic microenvironment.

PMID- 7515244
TI  - Analysis of MHC-presented peptides: applications in autoimmunity and vaccine
      development.
AB  - T cells recognize antigenic peptides presented on the cell surface by major
      histocompatibility complex (MHC) molecules. Here, Roman Chicz and Robert Urban
      describe the features of peptides bound to MHC molecules and the mechanism by
      which these surface proteins bind diverse peptide ligands with high affinity. In
      addition, they discuss the application of new technologies to the identification
      of MHC-associated peptides.

PMID- 7515247
TI  - Rehabilitation for the terminal cancer patient.
AB  - A study was made of 301 terminal cancer patients who received physical therapy in
      the hospice facility during a period of 6 1/2 years. Of 239 patients with
      activities of daily living disturbance, the average transfer and locomotion score
      on the Barthel mobility index (maximum score 47) was 12.4 before beginning the
      physical therapy program. Later, after activities of daily living exercises, at
      their maximum level these patients reached an average score of 19.9. Response to
      a questionnaire was obtained from 169 families of decreased patients; 149
      patients (88%) had indicated a desire for ambulation or mobility by wheelchair;
      166 patients (98%) were satisfied with the hospice care; 132 patients (78%) were
      satisfied with the rehabilitation in the terminal stage; 107 patients (63%)
      considered the terminal rehabilitation procedures to be effective. The more fully
      patients discussed the physical therapy program with the therapist, the more
      effective and more satisfactory the rehabilitation was judged to be. Families
      actively participating in the rehabilitation assessed it as more effective, more
      satisfactory to the patients and more useful in overall patient care than those
      who did not participate at all. This study shows that rehabilitation can make an
      important contribution to the care of the terminal cancer patient.

PMID- 7515246
TI  - Pretreatment with alpha 2-macroglobulin leads to recovery of rats exposed to a
      lethal scald.
AB  - The effect of alpha 2-macroglobulin (alpha 2M) administration on the survival
      rate of lethally injured rats and molecular mechanisms regulating its hepatic
      expression after sublethal and lethal scalding were examined. Transcriptional
      activity of nuclei for the alpha 2M gene increased after a sublethal 20 per cent
      TBSA scald reaching a maximal three-fold increase by 12 h, whereas concentrations
      of the corresponding mRNA and protein attained the maximal nine- and 18-fold
      enhancements by 24 h, respectively. After the second, lethal scald, the plasma
      alpha 2M level increased during the first few hours, then dropped rapidly below
      the control value although the abundance of its mRNA was several fold enhanced.
      This anomaly was ascribed to inhibition of the alpha 2M mRNA translation caused
      by the second scald-induced disturbance of the haemodynamic equilibria. Eighty
      per cent of rats receiving alpha 2M prior to rescalding survived the second
      injury. Their recovery proceeded in parallel with normalization of the plasma
      volume and reactivation of the process of acute phase protein synthesis in the
      liver. A functional link between these events is discussed.

PMID- 7515248
TI  - The sternomastoid island myocutaneous flap for oral cancer reconstruction.
AB  - OBJECTIVE: To evaluate the usefulness of the sternomastoid island myocutaneous
      flap for reconstruction of defects after excision of oral cancer. PATIENTS: One
      hundred eleven superiorly based sternomastoid island myocutaneous flaps were used
      for one-stage primary reconstruction in 110 consecutive patients with oral cancer
      during a 53-month period from June 1985 to November 1989. RESULTS: Ninety-eight
      patients had radiation therapy before surgery. One hundred six flaps were used
      for mucosal lining of the mouth and six flaps were used for providing skin cover.
      Flap-related complication developed in 38 patients (34.5%). Total flap loss
      occurred in eight patients (7.3%). Radical irradiation before surgery
      significantly increased flap-related complications. Low-molecular-weight dextran
      did not improve flap survival. After a minimum follow-up of 24 months, nine
      patients (8.2%) had recurrences in the ipsilateral neck. The flap could easily
      reach the oral cavity without producing tension on the suture line. The flap also
      did not produce excessive bulk in the mouth or on the face. CONCLUSION: In a
      selected group of patients with a clinically N0 neck, the sternomastoid island
      myocutaneous flap is oncologically safe and it gives satisfactory cosmetic and
      functional results with no lasting morbidity.

PMID- 7515249
TI  - Lymphoscintigraphy in pectoralis major myocutaneous flaps.
AB  - Myocutaneous flaps are used widely in the surgical treatment of advanced cancers,
      which in the past had been thought to be inoperable. Tumor recurrences are
      expected more frequently in these patients. Recurrent tumors may spread locally
      and to the regional areas via lymphatics and vessels. However, the lymphatic
      spread may differ in cases where myocutaneous flaps are used for reconstruction.
      This study is based on five patients with head and neck cancer who underwent
      reconstruction with myocutaneous flaps. Technetium Tc99m-labeled dextran was used
      to demonstrate the lymphatic flow, and technetium Tc99m rhenium sulfur colloid
      was used to show the lymph nodes of the neck and pectoralis major myocutaneous
      flap. Our findings show that the newly formed lymphatics do not pierce the
      fibrotic border of the donor and recipient sides. Lymphatic metastasis may occur
      to the internal mammary nodes through the myocutaneous flap only after recurrent
      tumors have invaded the myocutaneous flap directly.

PMID- 7515250
TI  - Myelin basic protein purification in non denaturing conditions.
AB  - The utilization of denaturing methods for protein purification causes the
      irreversible loss of quaternary and tertiary structure together with consistent
      changes in the secondary structure. These modifications reflect on protein
      antigenicity. MBP is a myelin protein which is bound to membrane-phospholipids.
      Its tertiary structure is specific for this kind of interaction which determines
      its native conformation. MBP was obtained in two forms: denatured and non
      denatured. The latter has been purified using the non-ionic detergent beta-octil
      D-glucopyranoside which is able to preserve protein tertiary structure separating
      it from the bilayer phospholipids. Non denaturated MBP could be useful in
      antibody and/or lymphocyte activity detection studies in various human
      pathological processes.

PMID- 7515251
TI  - Use of INT to determine the respiratory activity of immobilised and free
      Penicillium chrysogenum.
AB  - The specific oxygen uptake rates (OUR) of kappa-carrageenan-immobilised and free
      cell cultures of Penicillium chrysogenum were determined using an oxygen
      electrode in a closed chamber. This was compared with the respiratory activity
      determined by the extent of staining with iodo-nitrophenyl tetrazolium chloride
      (INT). The degree of INT staining correlated with the OUR; an increase in INT
      deposition corresponding to an increase in the measured OUR. The INT staining
      technique could therefore be used to determine cell respiratory activity. In this
      way a profile of fungal cell activity throughout immobilised cell aggregates and
      free cell pellets was determined. In both types of cell culture, after the
      initial growth period only the peripheral biomass was observed to be active.

PMID- 7515254
TI  - Early intervention: the professional views and referral practices of
      paediatricians in Victoria.
AB  - Early intervention services for young children with developmental disabilities
      have developed considerably in the past decade, yet little information is
      available about the referral practices and views of Australian paediatricians.
      During 1991, 100 paediatricians in Victoria completed a postal questionnaire
      designed to gain information regarding their attitudes to early intervention and
      referral practices. The results indicated that paediatricians had a positive view
      of early intervention, and perceived the standard and quality of the services in
      their region as comprehensive (16%) or adequate (54%). They were likely to make
      prompt referrals in the presence of an established disability (75%), but with
      suspected developmental delay, many (45%) were likely to wait until the delay was
      confirmed. Referrals were more often made for intervention for the child rather
      than for family support. However, paediatricians felt that early intervention had
      a beneficial effect on family functioning (81%). In general, the results indicate
      that there seem to be few barriers between paediatricians and the early
      intervention field.

PMID- 7515252
TI  - Absence of changes in metallothionein RNA in the rat testes made refractory to
      cadmium toxicity by zinc pretreatment.
AB  - Testicular toxicity and interstitial cell tumours induced by cadmium are
      prevented by zinc or by low dose cadmium pretreatments. The mechanism of this
      tolerance is unknown, though metallothionein (MT) is thought to play a role in
      tissue resistance to cadmium toxicity. Thus, the possible involvement of the
      testicular MT gene in metal-induced tolerance to cadmium toxicity was studied.
      Rats were pretreated with zinc (1.0 mmol kg-1, s.c.). Histological examination of
      the testes indicated such pretreatments prevented the necrotizing effects of
      subsequent doses of cadmium (20 mumol kg-1, s.c.) administered 24 h later. RNA
      was extracted from testes or liver 24 h after zinc pretreatment, and analysed by
      the slot blot technique using the p2A10 cDNA probe to the MT gene. Zinc
      pretreatment had little effect on MT RNA in the testes, and such pretreatments
      did not alter testicular cadmium-binding protein capacity. In contrast, RNAs
      derived from livers of zinc pretreated rats showed marked increases in MT RNA and
      MT protein. Hence, the testicular MT gene does not appear to play a major role in
      the induced tolerance to cadmium toxicity and carcinogenesis generated by zinc.

PMID- 7515253
TI  - Immunohistochemical studies on sympathetic and non-sympathetic nerve fibers and
      neuronal cell bodies in the pineal gland of cotton rats, Sigmodon hispidus.
AB  - Immunohistochemistry revealed the presence of tyrosine hydroxylase (TH)-,
      neuropeptide Y (NPY)-, calcitonin gene-related peptide (CGRP)- and substance P
      (SP)-immunoreactive nerve fibers and SP-immunoreactive neuronal cell bodies in
      the pineal gland of the cotton rat (Sigmodon hispidus). Abundant TH- and NPY
      immunoreactive fibers were distributed evenly throughout the gland; less numerous
      CGRP- and SP-immunoreactive fibers were distributed in the superficial pineal and
      the stalk, but were scarce in the deep pineal. All the immunoreactive fibers were
      usually found around blood vessels. Since TH- and NPY-immunoreactive fibers in
      various pineal regions disappeared completely with superior cervical
      ganglionectomy, these fibers are all considered postganglionic sympathetic
      fibers. Intrapineal CGRP- or SP-immunoreactive fibers decreased considerably in
      number following superior cervical ganglionectomy, suggesting that some
      sympathetic fibers contain CGRP or SP. Bilateral bundles of nerve fibers under
      the transverse sinuses, corresponding to the nervi conarii, contained TH-, NPY-,
      CGRP- and SP-immunoreactive fibers, which continued into those distributed in the
      pineal capsule. In the nervi conarii, fibers immunoreactive for TH and NPY
      disappeared after superior cervical ganglionectomy, but those immunoreactive for
      CGRP and SP persisted. Thus, non-sympathetic, CGRP- and SP-immunoreactive fibers,
      together with sympathetic fibers, are presumed to enter the gland by way of the
      nervi conarii. Neuronal cell bodies, containing SP-like immunoreactivity and
      being possibly parasympathetic in nature, occurred occasionally in the
      superficial pineal.

PMID- 7515255
TI  - Use of nasal mask CPAP instead of tracheostomy for palliative care in two
      children.
AB  - Nasal continuous positive airways pressure (nCPAP) is recommended in children for
      the treatment of obstructive sleep apnoea which persists following
      adenotonsillectomy. Nasal CPAP was successfully used in the palliative care of
      two severely disabled children with upper airway obstruction as an alternative to
      tracheostomy. Nasal CPAP resulted in the correction of obstructive apnoea in
      sleep, with the added benefit of sleep consolidation and fewer nocturnal arousals
      requiring parental attendance. There was also an unexpected benefit of reduced
      airway problems in the awake state in these children. Nasal CPAP is an effective
      form of treating upper airway obstruction for palliative care in association with
      other major disabilities.

PMID- 7515256
TI  - Interleukin 2-independent interleukin 7 activity enhances cytotoxic immune
      response of HIV-1-infected individuals.
AB  - Virus-specific cytotoxic T lymphocytes (CTLs), which kill virus-infected cells,
      are thought to be a major host defense against viral infections. The addition of
      interleukin 7 (IL-7) at the onset of mitogen-stimulated cultures resulted in a
      marked (up to threefold) augmentation of env-specific cytotoxicity in human
      immunodeficiency virus type 1 (HIV-1)-infected individuals (p < 0.001). Addition
      of IL-7 on day 3 or 5 produced a significant but lesser augmentation of CTL
      response as compared to day 0. The IL-7-induced proliferative response and
      augmentation of cytotoxic activity was time and dose dependent, with an optimal
      IL-7 concentration of 1000 U/ml. Cell surface phenotypic analysis of CTL effector
      cells indicates that IL-7 primarily affects the proliferation of CD8+ T cells.
      Anti-IL-2 monoclonal antibody (MAb) substantially inhibited the proliferative
      effect of IL-2, but did not affect the proliferative effect of IL-7. Endogenous
      IL-2-induced generation of cytotoxic T cells was blocked by MAbs to IL-2 or IL
      2R. The addition of IL-7 restored the process of conversion of precursor CTLs
      (pCTLs) to mature CTLs (mCTLs) and significantly enhanced specific cytolytic
      activity. It appears that IL-7 is a potent regulatory cytokine capable of acting
      independently of IL-2 in mitogen-specific activation of pCTLs to mCTLs. These
      data suggest that IL-7 should be considered as a potential therapeutic approach
      in AIDS and other infectious diseases in which CTL response declines.

PMID- 7515257
TI  - HIV-1 reverse transcription in cord blood lymphocytes: implications for infection
      of newborns.
AB  - We previously demonstrated that progeny virions are not produced after infection
      of adult quiescent peripheral blood lymphocytes (PBLs) by human immunodeficiency
      virus type 1 (HIV-1). Molecular analysis revealed that the nonproductive nature
      of this infection is due to failure to complete reverse transcription of the
      viral genome. In this study, we examined HIV-1 reverse transcription in quiescent
      lymphocytes from umbilical cord blood (CBLs). Using the polymerase chain reaction
      (PCR) to detect the presence of reverse transcription intermediates, we found
      that as in PBLs from adults, reverse transcription is not completed in quiescent
      CBLs; instead, a partial reverse transcript is formed. Quantitative PCR analysis
      also showed that fewer partial reverse transcripts were found in CBLs than in
      PBLs. Although the relevance of this restriction in reverse transcription to
      vertical transmission is unclear, these data suggest that the rapid progression
      of disease in infected children is not due to increased permissiveness of the
      lymphocytes of newborns for HIV-1 infection.

PMID- 7515258
TI  - Serial deletion mapping by competition ELISA assay: characterization of a linear
      epitope in the V3 loop of HIV-1.
AB  - Precise epitope mapping and characterization is important for development of a
      subunit vaccine. To identify epitopes in the principal neutralizing determinant
      (PND) within the V3 loop of human immunodeficiency virus type 1 (HIV-1), sera
      were screened in a direct ELISA assay with a coating peptide consisting of
      IHIGPGRAF, a specific sequence commonly found in the loop, linked at the C
      terminus to GAGAAK, a nonspecific hexapeptide. Epitope mapping experiments
      revealed that a competition ELISA assay using IGPGRAFGAGAAK as coating peptide
      was superior to a direct ELISA assay for epitope definition and characterization.
      The competing peptides contained only specific sequences and were serially
      deleted of single amino acids first at the N terminus and then at the C terminus.
      Study of the most highly reactive serum identified in the initial screening
      identified the epitope (the shortest peptide with the most potent inhibitory
      activity) as IGPGRAF. Deletion of a single amino acid from the C terminus of the
      epitope resulted in complete loss of activity as competing peptide. In contrast,
      single amino acid deletions of three N-terminal amino acids resulted in a
      stepwise 2700-fold reduction in affinity. RAF was the shortest peptide with
      inhibitory activity. Additional studies are needed, especially with regard to
      choice of coating peptide, to establish the general utility of the described
      epitope mapping procedure. However, the above method, termed serial deletion
      mapping, may be useful for defining and characterizing linear epitopes and thus
      may be particularly informative in investigating the multiple overlapping
      epitopes of the PND.

PMID- 7515259
TI  - Human antibodies to immunodominant C5 region of HIV-1 gp120 cross-react with HLA
      class I on activated cells.
AB  - Cross-reactive antibodies to HLA class I and HIV-1 gp120 were detected in the
      sera of HIV-1-positive individuals, and were found to share the same epitope
      specificity as a gp120-HLA class I cross-reactive monoclonal antibody (M38). The
      amino acid residues of HLA recognized by both M38 and the patient antibodies
      occur as a clustered pair in the HLA-C alpha 1 domain. These sequences (KYKR and
      RKLR) are shared by almost all HLA-C alleles and are available to antibody
      binding only on beta 2-microglobulin-dissociated HLA heavy chains expressed on
      activated cells. Similar to M38, the antibody-binding sites on HIV-1 gp120 were
      mapped to two noncontiguous stretches of amino acids (KYK and KAKR), which flank
      a hydrophobic area of the immunodominant C5 region involved in gp41 binding.
      Serum antibodies immunoaffinity purified on synthetic HLA and gp120 peptides
      representing the M38-reactive regions were shown to bind to both HLA and gp120 in
      Western blot, as well as to membrane-bound HLA heavy chains, and to exhibit
      selective complement-mediated lysis of activated T cells. No serum antibodies
      could be detected that bind to the gp120 C5 region (peptide IEPLGVAPT) flanked by
      the two HLA-like sequences.

PMID- 7515260
TI  - Randomised placebo controlled double blind study of two low dose aprotinin
      regimens in cardiac surgery.
AB  - OBJECTIVE: To determine whether two low dose aprotinin regimens produce
      clinically significant reductions in postoperative blood loss compared with a
      control group. DESIGN: A randomised double blind placebo controlled study.
      SETTING: A regional cardiothoracic unit in London. PATIENTS: 79 patients were
      consecutively allocated to one of three groups. All patients had primary elective
      surgery with standard anaesthetic and surgical techniques, and no patients were
      withdrawn from the study. INTERVENTIONS: Group K patients (n = 27) received
      aprotinin (10(6) kallikrein inactivator units (KIU) into the pump prime whereas
      group L patients (n = 27) received an intravenous bolus of aprotinin (0.5 x 10(6)
      KIU) after induction of anaesthesia and 10(6) KIU was added to the pump prime. A
      third group (group J, n = 25) received 0.9% saline placebo. MAIN OUTCOME
      MEASURES: After insertion of the chest drains at the end of cardiopulmonary
      bypass, blood losses were measured hourly until the drains were removed 18 to 24
      h later. Total haemoglobin loss into the chest drains was calculated. RESULTS:
      Both aprotinin treated groups showed significantly less postoperative blood loss
      than controls (medians: group K, 400 ml; group L, 400 ml; v controls 780 ml; p <
      0.001) and there was even less measured postoperative haemoglobin loss within the
      chest drains in both the aprotinin treated groups than in the controls (medians:
      group K, 16 g; group L, 19 g; v controls, 47 g; p < 0.001). CONCLUSION: In
      primary cardiac surgery the dose of aprotinin may be reduced by about 80% from
      the recommended high dose schedule and still significantly reduce postoperative
      blood loss compared with placebo.

PMID- 7515262
TI  - Long-term survival of stage A prostate carcinoma, atypical hyperplasia/adenosis
      and BPH.
AB  - Between 1972 and 1986, 134 patients with stage A carcinoma of the prostate (CAP)
      were diagnosed at a single Veterans Administration medical centre and followed
      annually by the hospital tumour registry. Seventy-four were classified as stage
      A1, defined as non-palpable, well-differentiated CAP, regardless of amount, found
      unexpectedly on transurethral resection of the prostate (TURP). Twenty-eight were
      classified as stage A2, defined as non-palpable, moderately or poorly
      differentiated CAP, regardless of amount, found unexpectedly on TURP. The
      remaining 32 were reclassified as atypical hyperplasia/adenosis (AH/A) rather
      than CAP. The survival of each group was compared with the survival of a control
      group from the same medical centre who had TURPs showing histologically proven
      benign prostatic hyperplasia (BPH). Survival and tumour progression were similar
      for patients with stage A1 CAP, AH/A and BPH. Furthermore, patients with stage A1
      CAP, with or without therapy, had similar survivals as patients with BPH in each
      age group (under 65, 65-74 and over 74 years). Stage A2 CAP was associated with a
      significantly worse survival and more tumour progression. Within stage A1 CAP and
      stage A2 CAP the percentage of chips with CAP or the amount of CAP removed did
      not affect survival.

PMID- 7515261
TI  - Characterisation of the differential expression of marker antigens by normal and
      malignant endometrial epithelium.
AB  - In order to examine the production of marker proteins, a reproducible method has
      been established for culturing purified epithelial cells from normal and
      malignant endometrium. We have examined the differential expression of secretory
      proteins using immunohistochemistry in frozen tissue sections,
      immunocytochemistry in cell cultures derived from the same specimens and protein
      assays on the culture supernatants. Placental protein 14 (PP14) was produced by
      normal premenopausal epithelium but not by the post-menopausal or malignant
      endometrial epithelium. In contrast, placental alkaline phosphatase (PLAP) was
      produced by endometrial cancers and the endometrial adenocarcinoma-derived cell
      line Ishikawa, but not by the normal endometrial epithelium. Other markers such
      as CA-125, which was produced by both normal and malignant endometrium but not by
      the cell line, and human chorionic gonadotrophin (beta-hCG), which was produced
      by Ishikawa cells but not by any of the fresh tissues, were less cancer specific.
      Placental alkaline phosphatase is a direct product of endometrial cancers that
      can be readily assayed in serum using this two-site assay to test its clinical
      usefulness in monitoring patients at risk for endometrial cancer.

PMID- 7515267
TI  - Alpha and beta thalassaemia among Chinese children in Guangxi Province, P.R.
      China: molecular and haematological characterization.
AB  - We have studied nearly 100 patients with beta-thalassaemia major and 60 patients
      with Hb H disease who were attending the Haematology Clinic of Guangxi Medical
      College. Treatment of the patients was limited and only a few patients with beta
      thalassaemia major received blood transfusion(s). As a result, the severe anaemia
      has led to early death at 3-4 years for beta zero-thalassaemia homozygotes, and 8
      12 years for beta(+)-thalassaemia homozygotes. Four beta-thalassaemia alleles are
      responsible for nearly 90% of all beta-thalassaemia chromosomes. This information
      has resulted in the initiation of a prenatal testing programme at the local
      level. The patients with Hb H disease maintained a haemoglobin level of 6-10 g/dl
      and early death was infrequently observed. The --SEA deletion was the major type
      of alpha-thalassemia-1, while three smaller deletions (-2.7, -3.7 and -4.2 kb)
      and two nondeletional alpha-thalassaemia determinants (Hbs Constant Spring and
      Quong Sze) were the alpha-thalassaemia-2 types.

PMID- 7515264
TI  - Relationship of transforming growth factor beta 1 to extracellular matrix and
      stromal infiltrates in invasive breast carcinoma.
AB  - Transforming growth factor beta (TGF-beta) comprises a group of multifunctional
      regulatory proteins, whose effects include stimulation of extracellular matrix
      formation and modification of immune function. The presence of TGF-beta 1 and TGF
      beta 2 in invasive breast carcinomas has been determined and related to
      pathological features, the presence of fibronectin and tenascin and
      lymphocyte/macrophage infiltration, using immunohistochemistry. Differences were
      observed in the extent of reactivity within the same carcinoma and between
      tumours stained with an antibody detecting TGF-beta 1 ane one detecting TGF-beta
      plus TGF-beta 2, the latter having a higher level of reactivity. Prominent
      reactivity for TGF-beta 1 was associated with lymph node metastasis, (0.02 > P >
      0.01), increased detection of cellular fibronectin, fine stromal fibronectin
      staining, more prominent reactivity for tenascin (0.02 > P > 0.01), the presence
      of tumour-associated macrophage infiltration and altered ratios of CD4 and CD8
      lymphocyte populations, with CD8 lymphocytes predominating. These associations
      were not observed for carcinomas showing prominent staining with antibody
      detecting TGF-beta 2 as well as TGF-beta 1. The findings indicate that TGF-beta 1
      may have a role in invasion and metastasis of breast carcinomas.

PMID- 7515268
TI  - FLAG (fludarabine+cytosine arabinoside+G-CSF) induces complete remission in acute
      phase chronic myeloid leukaemia: a case report.
AB  - The adenine nucleoside analogue fludarabine phosphate in combination with
      cytosine-arabinoside (Ara-C) and granulocyte-colony stimulating factor (G-CSF)
      has recently proved effective in the treatment of poor-prognosis acute non
      lymphoid leukaemia. We used this triple combination in a case of Ph1+ chronic
      myeloid leukaemia (CML) unresponsive to alpha interferon that had progressed to
      acute phase after 5 months of treatment with 6-mercaptopurine plus hydroxyurea.
      The patient was treated with four courses of fludarabine 30 mg/m2 + Ara-C 2 g/m2
      (days 1-5) and G-CSF (from day 0 to polymorphonuclear (PMN) recovery). Bone
      marrow blasts decreased from 80% to less than 5%, and karyotyping showed a
      progressive clearance of Ph1+ metaphases (from 100% to 9% after the fourth
      course). The patient is presently receiving autologous bone marrow
      transplantation (ABMT). This therapeutic success in a patient for whom
      conventional treatment would usually be ineffective makes this combination worthy
      of further studies, in view of its wider use as a preparative regimen to ABMT in
      CML.

PMID- 7515266
TI  - Collagenase activity and collagenase-inhibitory factors of serum and bone marrow
      fibroblast-conditioned medium in chronic myelogenous leukaemia.
AB  - Chronic myelogenous leukaemia (CML) is frequently accompanied by progressive
      myelofibrosis that is probably largely due to increased collagen production by
      bone marrow fibroblasts or decreased collagen degradation by collagenase. We
      investigated the activity of collagenase and collagenase-inhibitory factors (CIF)
      in serum and bone marrow fibroblast-conditioned medium obtained from patients
      with CML and healthy volunteers. The activity of both collagenase and CIF was
      significantly higher in the CML patients than in the normal volunteers. Our
      previous study showed that bone marrow fibroblasts from CML patients produce
      significantly more collagen than fibroblasts from normal subjects. Therefore, it
      appears that the in vitro production of collagenase and CIF by bone marrow
      fibroblasts is related to the degree of in vivo collagen production. and that
      both the increased collagenase and CIF activities are reflections of collagen
      overproduction in CML.

PMID- 7515263
TI  - Frequency of raised alpha-fetoprotein level among Chinese patients with
      hepatocellular carcinoma related to hepatitis B and C.
AB  - Antibody to hepatitis C virus (anti-HCV) was found to be an independent risk
      factor for hepatocellular carcinoma and raised serum alpha-fetoprotein (AFP)
      level. In addition, the frequency of raised AFP in patients with anti-HCV was
      higher than in those without (91.5% vs 65.2%, P = 0.0001).

PMID- 7515269
TI  - Sweet's syndrome in myeloid malignancy: a report of two cases.
AB  - Two patients with a myeloid malignancy in whom Sweet's syndrome (acute febrile
      neutrophilic dermatosis) was diagnosed, are described. They suffered from fever
      and showed cutaneous lesions, with infiltration of the skin by mature neutrophils
      without signs of vasculitis. In one of them the clonal origin of the infiltrating
      neutrophils could be demonstrated by in situ hybridization. In this patient an
      association with the use of recombinant human granulocyte-colony stimulating
      factor was suspected. In the other patient, Sweet's syndrome was the initial
      symptom of haematological disease. Inadequate wound healing after surgical
      procedures led to the diagnosis.

PMID- 7515265
TI  - Endogenous haemopoietic growth factors in neutropenia and infection.
AB  - Haemopoietic growth factors (HGFs) are being administered to patients with
      neutropenic fever; however, little is known about the endogenous HGF response in
      these patients. Specific assays were used to study four HGFs, granulocyte (G-)
      CSF, granulocyte-macrophage (GM-) CSF, macrophage (M-) CSF and interleukin (IL-)
      6 levels in the blood of patients with neutropenic fever (46 episodes). For
      comparison, levels were also measured in three control populations: normals (20),
      afebrile neutropenic (14), and bacteraemic but not neutropenic patients (20). In
      febrile patients, levels of G-CSF (median, range) (0.46, < 0.10-142 ng/ml). IL-6
      (0.054, 0.005-24.3 ng/ml) and M-CSF (18.5, 9.9-79.1 ng/ml) were elevated compared
      with afebrile subjects (< 0.10, < 0.10-1.62 ng/ml). (0.008, 0.002-0.024 ng/ml)
      and (6.45, < 5.0-31.3 ng/ml) respectively. GM-CSF was not elevated (< 0.02, <
      0.02-8.0 ng/ml) compared with afebrile subjects (0.021, < 0.02-0.20 ng/ml).
      Variables significantly associated (P < 0.05) with elevated cytokine levels were
      determined by multiple regression analyses. Factors associated with G-CSF
      elevation were fever, neutropenia, pathogen type and raised bilirubin and
      creatinine. In contrast, neutropenia was not associated with IL-6 elevation
      although there was an association between IL-6 elevation and fever, Gram-negative
      and fungal infections and raised creatinine and bilirubin. M-CSF elevation was
      associated with fever, renal impairment and known pathogen. Elevated G-CSF and IL
      6 levels normalized rapidly (hours-days) with the resolution of infection,
      whereas M-CSF concentrations remained elevated for up to 10 d. Cytokine levels
      remained elevated in septic neutropenic patients who did not recover. In summary,
      G-CSF, IL-6 and M-CSF levels were significantly elevated in sepsis. In contrast,
      GM-CSF levels were not elevated. These studies should assist the development of
      therapeutic strategies using HGFs in the treatment of sepsis.

PMID- 7515272
TI  - Control genes for reverse transcriptase/polymerase chain reaction (RT-PCR)

PMID- 7515270
TI  - Platelet aggregation in response to four low molecular weight heparins and the
      heparinoid ORG 10172 in patients with heparin-induced thrombocytopenia.
AB  - A simple rapid platelet aggregation test was used to evaluate cross-reactivity of
      four low molecular weight heparins and the heparinoid ORG 10172 in three patients
      with heparin-induced thrombocytopenia. The low molecular weight heparins cross
      reacted in 11 out of 12 tests. The heparinoid ORG 10172 did not cross-react in
      any of the patients. One patient was treated with ORG 10172 and thrombocytopenia
      resolved.

PMID- 7515271
TI  - Haemopoietic progenitor cells are reduced in aplastic anaemia.
AB  - We investigated the frequencies of early populations of progenitors in aplastic
      anaemia (AA) bone marrow, from patients with a range of disease severity,
      compared with normal. Double-colour immunofluorescent staining for CD34 and CD33
      was carried out on bone marrow mononuclear cells (BMMC) and analysed using
      fluorescence activated cell sorting (FACS). AA CD34+ cells were reduced by 68%
      compared to normal. In addition, AA CD33+ cells and the three progenitor subsets
      (CD34+/CD33-, CD34+/CD33+ and CD34-/CD33+) were reduced by 44-80%. Our data lend
      further support for an early stem cell deficiency in AA.

PMID- 7515273
TI  - Neutrophil increment after single injection of CSF.

PMID- 7515275
TI  - Congenital biliary dilatation with pancreatico-biliary maljunction: a comparative
      study between children and adults.
AB  - A comparative study of congenital biliary dilatation with pancreatico-biliary
      maljunction in 15 children and 16 adults was undertaken. Cystic and fusiform
      dilatation of the common bile duct was seen in 9 and 6 cases respectively in the
      child group, with 8 and 8 cases respectively in the adult group.
      Cholangiographically, neither the length of the common channel nor the type of
      pancreatico-ductal union varied significantly between groups. Furthermore the
      incidence of higher amylase levels of bile showed no apparent variance from group
      to group. This was also true when looking histologically at the number and
      distribution of periductal glands surrounding the intra-hepatic bile duct.
      Therefore, we concluded that there was no essential etiological difference
      between the two groups.

PMID- 7515274
TI  - Fetal lymphocyte subpopulations in red blood cell iso-immunised pregnancies.
AB  - OBJECTIVE: To study the association between fetal anaemia and alterations in
      lymphocyte subpopulations. DESIGN: Cross-sectional study. SETTING: The Harris
      Birthright Research Centre for Fetal Medicine, King's College Hospital Medical
      School, London. SUBJECTS: Forty-three red blood cell iso-immunised pregnancies
      undergoing cordocentesis at 19 to 38 weeks gestation. MAIN OUTCOME MEASURES:
      Fetal blood haemoglobin concentration, erythroblast count and lymphocyte
      subpopulations. RESULTS: The mean T (CD3+), B (CD19+), T-helper (CD4+), T
      suppressor/cytotoxic (CD8+) and natural killer (NK: CD16+/CD56+) cell counts in
      the anaemic fetuses were significantly lower than the appropriate normal mean for
      gestation (CD3+: t = -3.25, P < 0.01; CD19+: t = -2.14, P < 0.05; CD4+: t -4.03,
      P < 0.001; CD8+: t = -3.39, P < 0.01 and CD16+/CD56+: t = -3.49, P < 0.01).
      Furthermore, there was a significant association between the decrease in T
      lymphocyte number and the degree of fetal anaemia (r = 0.342, P < 0.05).
      CONCLUSIONS: Fetuses from red blood cell iso-immunised pregnancies exhibit
      nonselective lymphopenia that is proportional to the degree of anaemia.

PMID- 7515276
TI  - Keratinizing ameloblastomas.

PMID- 7515277
TI  - Lysophosphatidylcholine increases vascular superoxide anion production via
      protein kinase C activation.
AB  - We tested the hypothesis that lysophosphatidylcholine (lyso-PC) could activate
      protein kinase C in intact vascular segments and sought to examine some of the
      physiological consequences of this activation. In segments of rabbit aorta, the
      patterns of protein phosphorylation determined by two-dimensional electrophoresis
      stimulated by lyso-PC and 12-O-tetradecanoylphorbol 13-acetate (TPA) were
      similar. Activation of protein kinase C can stimulate superoxide anion (O2-)
      production in other tissues, and we found that lyso-PC-treated rabbit aortas
      produced twofold more O2- than control vessels. Calphostin C, a potent and
      specific inhibitor of protein kinase C, attenuated O2- production in lyso-PC
      treated vessels but had no effect in control vessels. The effect of lyso-PC on O2
      production was mimicked by TPA. In separate bioassay studies, release of the
      endothelium-derived vascular relaxing factor (EDRF) quantified by the response of
      detector vessels was markedly impaired after exposure of donor rabbit aortic
      segments to lyso-PC. After incubation with calphostin C, EDRF release in response
      to acetylcholine from lyso-PC-treated donor vessels was restored significantly.
      Thus, lyso-PC can activate protein kinase C in intact vessels, leading to an
      increase in O2- production. Activation of protein kinase C by lyso-PC may also
      play a role in altering the release of EDRF in response to acetylcholine.
      Increased O2- production in response to lyso-PC may have important consequences
      in the atherogenic process.

PMID- 7515278
TI  - Mast cells of two types differing in neutral protease composition in the human
      aortic intima. Demonstration of tryptase- and tryptase/chymase-containing mast
      cells in normal intimas, fatty streaks, and the shoulder region of atheromas.
AB  - Biochemical studies in vitro have demonstrated that stimulated mast cells induce
      macrophage foam cell formation through the synergistic action of mast cell
      granule neutral proteases and proteoglycans. To determine the presence and number
      of mast cells in human arterial intima, the site of atherogenesis, specimens of
      normal and atherosclerotic human aortic intima from 35 autopsies of persons
      ranging from 13 to 67 years old were stained with monoclonal antibodies against
      the two major proteases of mast cells, tryptase and chymase. All mast cells
      present were found to contain tryptase, and an average of 40% contained chymase
      as well. In sections of normal intimas, fatty streaks, and atheromas, the mast
      cells had average densities of 15/mm2, 15/mm2, and 3/mm2, respectively. In
      contrast to the normal intimas and fatty streaks, however, the atheromas had mast
      cells distributed unevenly in a typical pattern: 8/mm2 in the shoulder region,
      1/mm2 in the fibrous cap, and none in the core region. In normal intimas, fatty
      streaks, and the shoulder region of atheromas, the mast cells amounted to 3% of
      all nucleated cells. The ratios of mast cells to T lymphocytes and to
      macrophages, respectively, were 2:1 and 1:4 in normal intimas, 1:3 and 1:10 in
      fatty streaks, and 1:5 and 1:20 in the shoulder region of atheromas. Thus, among
      the blood-borne cells in the human aortic intima, mast cells compose a
      significant cell population, and in terms of their protease content, these
      intimal mast cells are heterogeneous.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515279
TI  - Structural domain of apolipoprotein A-I involved in its interaction with cells.
AB  - Apolipoprotein A-I (apo A-I) is the major protein constituent of high-density
      lipoprotein (HDL), the lipoprotein fraction which mediates the reverse
      cholesterol transport. This apolipoprotein plays an important role in the binding
      of HDL to cells and participates in the efflux of cellular cholesterol. We have
      recently compared six different genetic variants of apo A-I and found that the
      apo A-I (Pro 165-->Arg) mutant is defective in promoting cellular cholesterol
      efflux from murine adipocytes and peritoneal macrophages and we have proposed
      that this region of apo A-I may be involved in their interaction with cells. To
      confirm this hypothesis, four monoclonal antibodies (mAbs) specific for apo A-I
      were used to study the inhibition of the interaction of
      palmitoyloleoylphosphatidylcholine (POPC): apoA-I complexes with HeLa cells and
      adipocytes. Among these antibodies, the apo A-I epitope recognized by the A44 mAb
      lies in the COOH terminal region (amino acid residues 149-186) including the
      proposed region. The antibodies A05, and A03 react with residues 25-82, 135-140,
      respectively and the A11 mAb corresponds to a discontinuous epitope at residues
      99-105 and 126-132. Our results show clearly that the A44 and A05 mAbs reduce
      both the binding to HeLa cells and the cholesterol efflux from adipocytes. The
      inhibition of POPC: apoA-I complexes binding to both cell types is more strictly
      observed with the Fab fragments of monoclonal antibodies A44 and A05. Partial
      cotitration curves of these mAbs in a solid phase assay (RIA), indicated partial
      competition between these two antibodies. We propose a structural model for the
      POPC: apoA-I complexes where the N-terminal domain of one apo A-I molecule is in
      close spatial relationship with the C-terminal domain of the adjacent apo A-I
      molecule. We therefore suggest that the domain around amino acid 165 of apo A-I
      and which is recognized by mAb A44 (149-186) forms or contains some specific
      regions which mediate selectively the interaction with the binding site of cells
      and is involved in the efflux of cellular cholesterol.

PMID- 7515280
TI  - In vivo activities of acidic fibroblast growth factor-Pseudomonas exotoxin fusion
      proteins.
AB  - Fibroblast growth factor receptors are highly expressed in a variety of cancer
      cells and activated vasculature. Using chimeric toxins targeted to cell-surface a
      FGF receptors, we have demonstrated specific cytotoxic activity to these cell
      types. These molecules, aFGF-PE40 and aFGF-PE40 KDEL, are fusion proteins
      containing acidic FGF and either a 40- or a 66-kDa binding defective form of
      Pseudomonas exotoxin, respectively. Both aFGF-toxin fusion proteins were able to
      inhibit protein synthesis in vitro in a variety of carcinoma cell lines. The half
      life of aFGF-PE40 in serum was found to be 41 min when coadministered with
      heparin. Administration of aFGF-PE40 or aFGF-PE4E KDEL with heparin inhibits the
      growth of established KB and preestablished A431 epidermoid carcinoma xenografts
      in athymic mice. The antitumor activities of the two aFGF-toxin fusion proteins
      were equivalent against the KB tumor xenografts. While we were able to slow the
      growth of the KB tumor xenografts, we were unable to cause tumor regressions.
      Histochemical analysis of treated versus untreated tumor tissue revealed a
      difference in tumor size but not of vascularity. We conclude that aFGF-PE40 and
      aFGF-PE4E KDEL have in vivo antitumor activity that targets the tumor cell mass
      rather than vascular structures in mice xenografted with human epidermoid
      carcinoma.

PMID- 7515281
TI  - Carboxymethyldextran lactone: a preactivated polymer for amine conjugations.
AB  - The linking of amino haptens to carboxymethyldextran (CMD) requires carboxyl
      activation, for example, via carbodiimdes. We have discovered that substantial N
      acylurea, derived from these carbodiimides, can be trapped on the CMD backbone.
      As an alternative, CMD can be conveniently lactonized by heating in inert
      solvents, and this carboxymethyldextran lactone (CLD) can be employed directly
      for amine conjugation.

PMID- 7515282
TI  - Mammalian tryptophanyl-tRNA synthetases.
AB  - Aminoacyl-tRNA synthetases of higher organisms are far less studied compared to
      their prokaryotic and unicellular eukaryotic counterparts. However, many
      aminoacyl-tRNA synthetases from multi-cellular organisms exhibit certain features
      not yet described for the same enzymes of bacteria or yeast. Tryptophanyl-tRNA
      synthetases (TrpRS) are among the most thoroughly studied mammalian enzymes of
      this group. TrpRS are Zn(2+)-dependent, dimeric, class I aminoacyl-tRNA
      synthetases with known amino acid sequence for four different mammalian orders.
      TrpRS is not associated in a stable multi-synthetase complex, although it
      exhibits a long N-terminal extension absent from bacterial TrpRS. The human gene
      encoding TrpRS belongs to the interferon-responsive gene family and TrpRS
      activity drastically increases after interferon gamma induction. For unknown
      reasons TrpRS is overproduced in pancreas of Ruminantia. Other data on TrpRS
      available so far are summarized and briefly discussed here.

PMID- 7515283
TI  - Relationship between the structure and function of Escherichia coli initiator
      tRNA.
AB  - Through functional studies of mutant tRNAs, we have identified sequence and/or
      structural features important for specifying the many distinctive properties of E
      coli initiator tRNA. Many of the mutant tRNAs contain an anticodon sequence
      change from CAU-->CUA and are now substrates for E coli glutaminyl-tRNA
      synthetase (GlnRS). We describe here the effect of further mutating the
      discriminator base 73 and nucleotide 72 at the end of the acceptor stem on: i)
      recognition of the mutant tRNAs by E coli GlnRS; ii) recognition by E coli
      methionyl-tRNA transformylase; and iii) activity of the mutant tRNAs in
      initiation in E coli. For GlnRS recognition, our results are, in general,
      consistent with interactions found in the crystal structure of the E coli GlnRS
      glutamine tRNA complex. The results also support our previous conclusion that
      formylation of initiator tRNA is important for its function in initiation.

PMID- 7515285
TI  - Expression of the genes for the epidermal growth factor receptor and its ligands
      in porcine oviduct and endometrium.
AB  - We have used the reverse transcription-polymerase chain reaction (RT-PCR) to
      determine whether transcripts for the epidermal growth factor (EGF) receptor and
      its four known ligands--EGF, transforming growth factor alpha (TGF alpha),
      amphiregulin (Ar), and heparin-binding EGF (HB-EGF)--are expressed in porcine
      oviduct and endometrium. We were able to detect mRNA for the EGF receptor, EGF,
      TGF alpha, and Ar in both the oviduct and endometrium, whereas HB-EGF mRNA was
      not detectable in either tissue. Through use of an antiserum raised against
      recombinant pig EGF, expression of EGF was found to be localized to the columnar
      epithelial cells of the oviduct and to the glandular epithelial cells of the
      endometrium. The possible physiological roles of the EGF family in the
      reproductive tract are discussed.

PMID- 7515286
TI  - Differential regulation of cyclic adenosine 3',5'-monophosphate (cAMP) response
      element-binding protein and cAMP response element modulator messenger ribonucleic
      acid transcripts by follicle-stimulating hormone and androgen in the adult rat
      testis.
AB  - Hormonal regulation of the expression of mRNA transcripts for cAMP response
      element-binding protein (CREB) and cAMP response element modulator (CREM) during
      spermatogenesis was studied in the adult rat testis. Northern analysis of CREB
      and CREM identified two mRNA transcripts for CREM (2.4 and 1.6 kb) and one
      transcript for CREB (2.0 kb). Analysis of mRNAs from isolated testicular cells by
      reverse transcriptase polymerase chain reaction (RT/PCR) showed that CREM mRNAs
      were expressed by the germ cells but not the Sertoli or interstitial cells,
      whereas CREB mRNA was located in germ cells, Sertoli cells, and interstitial
      cells. RNA was isolated and analyzed from the testes of 1) rats treated for 24 h
      with FSH, 2) rats in which androgen withdrawal had been induced by ethane
      dimethane sulphonate (EDS) treatment 6 days earlier (EDS-treated), 3) EDS-treated
      rats supplemented with testosterone (EDS + T), or 4) intratesticular
      administration or dibutyryl cAMP (dbcAMP) in the preceding 24 h. CREM mRNA
      transcript expression was found to be decreased after all of these treatments in
      samples from intact testis and from isolated cells. Expression of the CREB
      transcript was also decreased by EDS-induced androgen withdrawal, but not by FSH
      or EDS + T. In situ hybridization of paraffin-embedded testis sections probed
      with digoxigenin-labeled riboprobes confirmed the localization of CREB and CREM
      mRNA to the same cell types as found with RT/PCR. No stage-dependent expression
      of CREM mRNA transcripts could be observed. Hybridization of the CREB probe was
      highest around the base of stage VII-VIII tubules, and this was shown to be
      androgen-dependent. The data presented suggest that regulation of the expression
      of CRE-binding protein mRNAs in Sertoli and germ cells during spermatogenesis is
      dependent on both androgen and FSH. However, the effects of androgen or FSH on
      the regulation of CRE-binding protein mRNAs are different.

PMID- 7515284
TI  - A growth factor phenotype map for ovine preimplantation development.
AB  - The reverse transcription-polymerase chain reaction (RT-PCR) was used to
      determine the patterns of expression for several growth factor ligand and
      receptor genes during ovine preimplantation development. Transcripts for insulin
      like growth factor (IGF)-I, IGF-II, and the receptors for insulin and IGF-I were
      detected throughout ovine preimplantation development from the 1-cell to the
      blastocyst stage. Transforming growth factor alpha (TGF alpha) transcripts were
      also detected throughout ovine preimplantation development. The mRNAs encoding
      basic fibroblast growth factor (bFGF) were detected in all stages of the ovine
      preimplantation embryo, although the relative abundance of this transcript
      consistently decreased from the 1-cell to the blastocyst stage, suggesting that
      it may represent a maternal transcript in early sheep embryos. Transcripts
      encoding ovine trophoblast protein (oTP) were detected only within blastocyst
      stage embryos. Primary ovine oviduct cell cultures express the transcripts for
      IGF-II, IGF-I, TGF alpha, bFGF, TGF beta 1, and the receptors for insulin and IGF
      I, suggesting that paracrine growth factor circuits may exist between the oviduct
      epithelium and the early ovine embryo. Transcripts for insulin, epidermal growth
      factor (EGF), and nerve growth factor (NGF) were not detected in any stage of the
      ovine preimplantation embryo or within the oviduct cell preparations. The
      expression of growth factor transcripts very early in mammalian development would
      predict that these molecules fulfil a necessary role(s) in supporting the
      progression of early embryos through the preimplantation interval. Our future
      efforts will be directed to understanding the nature of these putative regulatory
      pathways.

PMID- 7515289
TI  - Histochemical and confocal laser scanning microscopy study of the bone-titanium
      interface: an experimental study in rabbits.
AB  - The aim of our study was an analysis of the presence of an unmineralized bone
      matrix between mineralized bone and titanium screws in rabbit tibiae. A
      microscopical analysis, using a histochemical technique, was performed on the
      titanium-bone interface of commercially pure titanium implants placed in rabbit
      tibiae and harvested after 2 months. Thin ground sections of the specimens were
      prepared by the cutting-grinding system and stained using the von Kossa method
      for calcium salts and basic fuchsin for osteoid. The microscopical and
      morphometrical evaluation showed that bone covered about 40% (+/- 7.5%) of all
      implants. Mineralized bone was, however, in direct contact with the titanium
      surface on only about 10% of the implant, while in the remaining 30% the
      mineralized bone was separated from the implant by an unmineralized tissue. This
      basophilic, probably osteoid matrix, could represent the medium that allows the
      biochemical exchanges between bone and cells under the influence of the implant.
      A small, optically translucent gap (1-5 microns), probably an artifact, was
      present in some areas between titanium and bone. Confocal laser scanning
      microscopy (CLSM) in a fluorescent mode showed the presence at the interface of a
      fluorescent material. Results from our study showed that light microscopy of thin
      ground sections allowed a good analysis of the real nature of the titanium-bone
      interface. Moreover, this double staining technique showed the presence of an
      unmineralized bone matrix at most of the bone-titanium interface.

PMID- 7515287
TI  - Expression of leukemia inhibitory factor in human endometrium and placenta.
AB  - Leukemia inhibitory factor (LIF), a cytokine that induces macrophage
      differentiation in the murine M1 myeloid leukemia cell line, is essential for
      blastocyst implantation in mice. However, its expression and the role it plays in
      the human uterus are unknown. To clarify these issues, we examined LIF gene
      expression in the human uterus by Northern blot hybridization and by a
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) method.
      Analysis of LIF mRNA showed two hybridization bands, with estimated mRNA sizes of
      about 4.0-kb pairs and 1.8-kb pairs. LIF mRNA was detected at high levels in
      endometrial tissue and decidua, but at low levels in the chorionic villus in
      first trimester and term placenta. In the secretory phase, the endometrial tissue
      showed higher LIF expression than in the proliferative phase (9.5-fold; p <
      0.01). The endometrial tissues were separated into a stroma-enriched fraction
      (SF) and an epithelium-enriched fraction (EF), and the LIF mRNA levels in each
      fraction were examined by quantitative RT-PCR. These levels were higher in the EF
      than in the SF (3.3-fold; p < 0.05). These findings suggest that, in humans, LIF
      plays a role in uterine function during the menstrual cycle, as well as during
      pregnancy.

PMID- 7515288
TI  - A major messenger ribonucleic acid of the rodent epididymis encodes a small
      glycosylphosphatidylinositol-anchored lymphocyte surface antigen.
AB  - The adult rodent epididymis and seminal vesicles were shown by polymerase chain
      reaction (PCR) cloning. Northern blot analysis, and in situ hybridization to be
      major expression sites of an mRNA encoding a small glycosylphosphatidylinositol
      (GPI)-anchored cell surface antigen that has been previously described as the
      mouse lymphocyte differentiation antigen B7, herein referred to as MB7. Sequence
      comparison of the corresponding epididymal cDNAs from the mouse (MB7) and the rat
      (RB7) revealed an unexpected divergence in the peptide coding regions of these
      homologous genes. A possible functional relationship to the human sperm surface
      and lymphocyte differentiation antigen CDw52/HE5 is discussed with respect to the
      highly variable mature peptide coding regions.

PMID- 7515290
TI  - Mechanism of initial attachment of cells derived from human bone to commonly used
      prosthetic materials during cell culture.
AB  - The suitability of polymeric biomaterials as surfaces for the attachment and
      growth of cells has often been investigated in cell culture. In this study the
      contribution that serum fibronectin (Fn) or vitronectin (Vn) make to the
      attachment and spreading of cells cultured from explanted human bone (bone
      derived cells) during the first 90 min of culture was determined for metallic and
      ceramic surfaces. The requirement for Fn or Vn for attachment and spreading of
      bone-derived cells onto stainless steel 316 (SS), titanium (Ti) and alumina
      (Al2O3) and to polyethyleneterephthalate (PET) was directly tested by selective
      removal of Fn or Vn from the serum prior to addition to the culture medium.
      Attachment and spreading of bone-derived cells onto SS, Ti and Al2O3 surfaces
      were reduced by 73-83% when the cells were seeded in medium containing serum from
      which the Vn had been removed. Cell attachment and spreading on these surfaces
      when seeded in medium containing Fn-depleted serum (which contained Vn) were not
      reduced to the same extent as in the medium containing Vn-depleted serum. The
      bone-derived cells failed to attach to the surfaces to the same extent when
      seeded in medium containing serum depleted of both Vn and Fn. Our results show
      that for human bone-derived cells, the attachment and spreading of cells onto SS,
      Ti and Al2O3 as well as PET during the first 90 min of a cell culture attachment
      assay are a function of adsorption of serum Vn onto the surface.

PMID- 7515291
TI  - A new detergent to purify CNS myelin basic protein isoforms in lipid-bound form.
AB  - We have previously shown that CNS myelin basic protein (MBP) can be purified in
      the lipid-bound, native-like form by using a procedure based on myelin
      solubilization with detergents at pH above 7, and on the filter-like use of
      hydroxyapatite to separate non-adsorbed MBP from other myelin proteins. Here, we
      report on the isolation of MBP in the zwitterionic detergent 3-((3
      cholamidopropyl)dimethylammonio)-1-propane sulfonate (CHAPS), which does not
      interfere at 280 nm and can be removed by dialysis. This detergent appears to
      improve MBP purification and to be suitable for fluorescence and reconstitution
      studies that can be useful to understand both structure and function of MBP in
      its natural environment.

PMID- 7515292
TI  - Release of nitric oxide by nerve stimulation in the human urogenital tract.
AB  - Nerve-induced release of the nitric oxide (NO) breakdown products nitrite (NO2-)
      and nitrate (NO3-) and the histochemical localization of NO synthase in the human
      penile corpus cavernosum and urethra were studied. Relaxations induced by nerve
      stimulation were inhibited by N omega-nitro-L-arginine methyl ester (L-NAME), an
      effect which was reversed by L-arginine. Relaxations elicited either by nerve
      stimulation or exogenous NO were accompanied by the appearance of equivalent
      amounts of NO2- and NO3- over a very similar time course. Nerve-induced release
      of NO2- and NO3- was inhibited by L-NAME. Histochemical studies showed NADPH
      diaphorase and NO-positive nerve fibres surrounding the arteries and smooth
      muscle bundles in the corpus cavernosum and the urethra. The results suggest that
      NO is a mediator for non-adrenergic non-cholinergic relaxation in the human
      urogenital tract.

PMID- 7515293
TI  - Vascular endothelial growth factor and its receptors.
AB  - Vascular endothelial growth factor (VEGF) is a highly specific mitogen for
      vascular endothelial cells and an angiogenic factor that is structurally related
      to platelet derived growth factor (PDGF). It is also known as the vascular
      permeability factor (VPF) because it efficiently potentiates the permeabilization
      of blood vessels. Five types of VEGF mRNA encoding VEGF species which differ in
      their molecular mass and in their biological properties are transcribed from a
      single gene as a result of alternative splicing. VEGFs are produced and secreted
      by several normal cell types including smooth muscle, luteal and adrenal cortex
      cells. VEGFs are also produced by different tumorigenic cells, and appear to play
      a major role in tumour angiogenesis. Antibodies directed against VEGF can inhibit
      the growth of a variety of VEGF producing tumours. Of the various VEGF species,
      the best characterized is the 165 amino acid long form (VEGF165). VEGF165 is a
      heparin binding growth factor, and its interaction with VEGF receptors on the
      cell surface of vascular endothelial cells depends on the presence of heparin
      like molecules. Several cell types which do not proliferate in response to VEGF
      such as bovine corneal endothelial cells, HeLa cells and human melanoma cells
      also express cell surface VEGF receptors, but the function of the VEGF receptors
      in these cells is unclear. Recently, the tyrosine-kinase receptors encoded by the
      flt and KDR/flk-1 genes were found to function as VEGF165 receptors.

PMID- 7515294
TI  - Ole e I: epitope mapping, cross-reactivity with other Oleaceae pollens and
      ultrastructural localization.
AB  - Ole e I is the major allergen derived from olive tree pollen (Olea europaea) and
      it is composed of two polypeptides with molecular weights (MWs) of 18 and 20 kD.
      A panel of six monoclonal antibodies (mAbs) has been prepared and used to map
      antigenic determinants on this molecule. Four epitope determinants have been
      identified on Ole e I. Using the purified mAbs produced against Ole e I, we have
      analyzed the common epitope determinants in olive (O. europaea) and different
      Oleaceae pollens: ash (Fraxinus excelsior); privet (Ligustrum vulgare); lilac
      (Syringa vulgaris), and forsythia (Forsythia suspensa). ELISA showed three
      reactivity groups depending on the recognition of monoclonal antibodies: (1)
      olive and ash; (2) olive, ash, privet and lilac; and (3) olive, ash, privet,
      lilac and forsythia. Immunoblotting studies on Oleaceae pollen extracts with
      these mAbs showed a very similar cross-reactivity pattern. The 18- and 20-kD MW
      proteins were present in each pollen, except in the case of forsythia. In this
      case the reactivity pattern was associated with 50- to 55-kD protein bands. This
      band was recognized by a pool of sera from olive-allergic patients. Finally,
      ultrastructural localization of Ole e I antigen was performed on the mature olive
      pollen grain. Ole e I was located in association with dilated endoplasmic
      reticulum cisternae. Pollen grain walls, nuclei and cytoplasmic organelles were
      totally devoid of the allergen.

PMID- 7515296
TI  - Isolation and identification of two CD34+ cell subpopulations from normal human
      peripheral blood.
AB  - Circulating CD34+ progenitors were separated from normal human peripheral blood
      on the basis of size and density by counterflow centrifugal elutriation (CCE).
      The CD34+ cells, 0.15% of peripheral blood mononuclear cells, were heterogeneous
      with respect to their elutriation characteristics, mainly size and density. The
      least mature CD34+ cells, characterized by lack of CD38 antigen, were
      predominantly found in the small lymphoid cell fraction. In fractions containing
      larger and denser cells (large lymphocytes, monocytes, and granulocytes), CD38
      was increasingly expressed on the CD34+ cells, as were lineage commitment markers
      CD10 (B lymphoid), CD33 (myeloid), CD13 (myelomonocytic) and CD71 (erythroid)
      antigens. The smaller and less dense CD34+ cells expressed CD34 antigen brightly
      while the larger and denser CD34+ cells expressed it dimly. The smaller and less
      dense CD34+ high cells failed to establish colony growth in short-term culture
      while the larger and denser CD34+low cells gave rise to high counts of colony
      forming units-granulocyte macrophage (CFU-GM). Physical separation on the basis
      of size and density by CCE differentiates between two main classes of steady
      state CD34+ cells from normal human peripheral blood. The smaller and less dense
      CD34+high cells correspond to the earliest progenitors that express
      differentiation markers poorly but CD34 antigen brightly, do not give rise to
      short-term colony growth in vitro, and thus represent indirect evidence for
      pluripotent hematopoietic stem cells (PHSC). The larger and denser CD34+low cells
      are the more mature progenitor cells, already committed to myeloid, lymphoid or
      erythroid differentiation but only dimly expressing CD34 antigen, and these cells
      were responsible for short-term colony growth in vitro.

PMID- 7515297
TI  - c-kit ligand combined with GM-CSF and/or IL-3 can expand CD34+ hematopoietic
      progenitor subsets for several weeks in vitro.
AB  - It might be possible to facilitate engraftment after transplantation of purified
      hematopoietic progenitor cells if the cells are stimulated ex vivo prior to
      transplantation. The aim of this study was to analyze the potential of c-kit
      ligand (CKL) combined with granulocyte-macrophage colony-stimulating factor (GM
      CSF) and/or interleukin-3 (IL-3) to induce proliferation and differentiation of
      human bone marrow CD34+ cells in vitro. Particular attention was paid to the
      ability to expand populations that could maintain progenitor characteristics,
      i.e. CD34 expression and generation of colony forming cells (CFC), for a
      considerable period of time. Purified CD34+ cells were cultured in liquid medium
      for 42 days interrupted by immunophenotyping and CFC assays. In the presence of
      CKL combined with GM-CSF and/or IL-3, the total number of cells expressing CD34
      increased significantly for several weeks after an initial decline. Further, CFC
      were continually recovered in these cultures. Based on the kinetics and the flow
      cytometry analysis, the expanding populations that continued to express CD34
      probably originated from noncommitted, immature CD34+ cell subsets. CKL combined
      with GM-CSF and/or IL-3 also induced strong cell proliferation. The majority of
      the proliferating cells lost CD34 expression and acquired a series of mature
      myeloid cell surface markers associated with the monocytic, granulocytic and
      megakaryocytic lineages. These cells probably originated from committed CD34+
      cell subsets. We conclude that CKL combined with GM-CSF and/or IL-3 can stimulate
      noncommitted, immature as well as committed CD34+ cell populations to expand and
      to differentiate. This property might be useful in a short-term ex vivo
      pretransplant stimulation of CD34+ cells in an attempt to facilitate rapid and
      stable engraftment after stem cell transplantation.

PMID- 7515295
TI  - Determination of streptomycin and dihydrostreptomycin in animal tissue by on-line
      sample enrichment liquid chromatography.
AB  - A method for the determination of streptomycin and dihydrostreptomycin in pork
      and bovine muscle and kidney was developed. Dilute perchloric acid solution is
      used to precipitate proteins and extract the analytes from the tissue. The
      extract is loaded onto a cation-exchange, solid-phase extraction column, and the
      drugs are eluted with pH 8 phosphate buffer. The eluant is chromatographed by
      using an on-line column enrichment liquid chromatographic system with postcolumn
      derivatization using 1,2-naphthoquinone-4-sulfonic acid and detection by
      fluorescence. The recoveries were 61.1% (coefficient of variation [CV], 7.3%) for
      streptomycin and 55.3% (CV, 8.2%) for dihydrostreptomycin. The detection limits
      were 10 ppb for streptomycin and 20 ppb for dihydrostreptomycin.

PMID- 7515298
TI  - Recombinant human glycosylated granulocyte colony-stimulating factor (rhG-CSF)
      combined regimen for allogeneic bone marrow transplantation in refractory acute
      myeloid leukemia.
AB  - Recombinant human glycosylated G-CSF (rhG-CSF) may stimulate proliferation of
      myeloid leukemia cells and thereby increase their susceptibility to anti-cancer
      agents. By in vitro colony assay, the rhG-CSF-responsive NFS-60 leukemic cell
      clones are more effectively killed by Ara C in the presence of rhG-CSF than in
      the absence of rhG-CSF, while the killing of the rhG-CSF-unresponsive HL-60 cell
      clones is unaffected by rhG-CSF. Leukemia cell colony forming units (L-CFU)
      derived from most AML patients demonstrate similar results to those of the NFS-60
      cell clone when treated in vitro. Encouraged by these in vitro results, we used
      rhG-CSF as a component of a conditioning regimen for 15 relapsed AML patients who
      were receiving allogeneic BMT. The patients were conditioned with total body
      irradiation (TBI) and high-dose Ara C. rhG-CSF was infused continuously at a dose
      of 5 micrograms/kg/day from 24 h before the beginning of TBI to the end of Ara C
      therapy. Proliferation of the leukemia cells in vivo in response to rhG-CSF was
      confirmed in 7 of 14 patients tested and the combined use of rhG-CSF had no
      additional adverse effects. After BMT, four patients died of non-leukemic causes
      and three patients had leukemic relapse: the other eight patients have remained
      disease-free for 200-1600 (median 417) days. The actuarial probabilities of
      relapse and disease-free survival (DFS) at 4.4 years after BMT were 43.2% and
      41.7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515299
TI  - Tolerance of sequential or simultaneous administration of IL-3 and G-CSF in
      improving peripheral blood stem cells harvesting following multi-agent
      chemotherapy: a pilot study.
AB  - A pilot study was devised to assess tolerance of combined administration of
      interleukin-3 (IL-3) and granulocyte-colony stimulating factor (G-CSF) given
      after chemotherapy to mobilize peripheral blood progenitors cells (PBPC). Eight
      patients with advanced malignancies received 1 week courses of both IL-3 and G
      CSF in one of three schedules: simultaneous 7 days administration (3 patients),
      sequential administration (3 patients) or partial (3 days) overlap of the two
      growth factors (2 patients). IL-3 (7.5 micrograms/kg/day) and G-CSF (5
      micrograms/kg/day for the simultaneous schedule and 12 micrograms/kg/day for the
      partial overlapping and sequential schedules) were administered subcutaneously.
      Side-effects during cytokine administration included WHO grade I-II fever in 6 of
      8 patients, flu-like symptoms (including myalgias and arthralgias) in 4 of 8, WHO
      grade I-II headache in 2 of 8 and WHO grade II nausea and vomiting in 1 of 8.
      Overall, side-effects appeared similar during combined administration of IL-3 and
      G-CSF to those observed during administration of IL-3 alone. No fever was
      observed when G-CSF was administered alone. Two leukaphereses were performed
      following the treatment with cytokines. Only the seven patients who received
      cytokines following chemotherapy were analyzed for PBPC mobilization. The median
      collection of CFU-GM/kg per patient in the seven analyzed patients was 1.3 x
      10(5) (range 5.7 x 10(2)-3.6 x 10(5)). In two patients, a second cycle of
      mobilization with either granulocyte macrophage-colony stimulating factor (GM
      CSF) or G-CSF was administered to allow safe engraftment.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7515300
TI  - Effect of granulocyte colony-stimulating factor on hematopoietic recovery after
      peripheral blood progenitor cell transplantation.
AB  - To examine the effect of granulocyte colony-stimulating factor (G-CSF) on
      hematopoietic recovery after high-dose chemotherapy and peripheral blood
      progenitor cell transplantation (PBPCT), 20 patients with hematologic
      malignancies were divided into two groups. One group was given G-CSF at a daily
      dose of 50 micrograms/m2 subcutaneously, the other received no G-CSF. Neutrophil
      recovery was accelerated in the G-CSF treated patients and exceeded 0.5 x 10(9)/l
      at a median of 10 days post-PBPCT compared with 14 days in the control group (p <
      0.01). This reduction led to a decrease in antibiotic use and a trend toward
      fewer febrile days in the G-CSF treated group.

PMID- 7515301
TI  - Lack of effect of hematopoietic growth factors on human breast epithelial cell
      growth in serum-free primary culture.
AB  - A number of recombinant cytokines believed to regulate normal hematopoiesis are
      now being used in cancer treatment protocols to reduce the myelosuppressive
      toxicity of intensive chemoradiotherapy regimens. It is widely assumed that such
      cytokines are relatively specific for hematopoietic cells, although some cell
      lines derived from a variety of non-hematopoietic human tumors can respond to
      some of these factors. However, relatively little is known about their ability to
      stimulate (or inhibit) the proliferation of freshly isolated normal or malignant
      non-hematopoietic cells. We have used a serum-free culture medium that
      selectively supports the growth of human breast epithelial cells (HBEC) obtained
      directly from normal or malignant tissue samples to evaluate potential
      stimulatory or inhibitory effects of eight cytokines: granulocyte colony
      stimulating factor, granulocyte-macrophage colony-stimulating factor, Steel
      factor, interleukin-2, interleukin-3, interleukin-6, transforming growth factor
      beta and macrophage inflammatory protein-1 alpha, on these cells cultured both in
      the presence of epidermal growth factor, a potent stimulator of HBEC growth, and
      in its absence. HBEC growth was assessed after 7 and 14 days using the
      tetrazolium-dye reduction assay. Potential effects on the well studied MCF-7
      breast cancer cell line, cultured under the same conditions, were also
      investigated. None of the cytokines (which were tested over a wide range of
      concentrations) had any modulating effect on the growth of normal or malignant
      HBEC under the conditions used with the exception of transforming growth factor
      beta, which was consistently and significantly inhibitory.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7515302
TI  - Successful second autologous blood stem cell transplantation after G-CSF-combined
      conditioning for the treatment of high-risk acute myelogenous leukemia.
AB  - We describe a patient with acute myelogenous leukemia (AML) who received his
      second autologous blood stem cell transplantation (ABSCT) following a G-CSF
      combined pre-transplant conditioning regimen. The patient underwent ABSCT during
      first remission but suffered a relapse 8 months later. After achieving second
      remission, he was prepared for his second ABSCT; recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) was administered in combination with Ara C,
      in addition to the same conditioning regimen as that used before the first ABSCT.
      There was no increase in regimen-related toxicity after this second G-CSF
      combined conditioning regimen when compared with that observed after the first
      ABSCT. To date, the patient's second remission following the second ABSCT has
      lasted 26 months, which has exceeded that following the first ABSCT. The G-CSF
      combined pretransplant conditioning regimen for ABSCT may be effective in the
      treatment of high-risk AML by increasing the chemosensitivity of the residual
      leukemic cells.

PMID- 7515303
TI  - Identification of rare and novel mutations in the CFTR genes of CF patients in
      southern England.
AB  - Cystic fibrosis patients referred to two genetics centres in southern England and
      not found to carry common CF-associated mutations in one or both of their CFTR
      genes have been subjected to an extensive mutation search. The whole of the
      coding region of the CFTR gene, all intron-exon boundaries and 5' and 3'
      untranslated regions have been examined by a combination of single stranded
      conformational polymorphism analysis and chemical mismatch detection; 48
      chromosomes with rare mutations have been identified, including 7 novel
      mutations, 182delT in exon 1, G27X in exon 2, Q151X in exon 4, Q220X in exon 6a,
      Q525X in exon 10, 3041delG in exon 16, and 4271delC in exon 23.

PMID- 7515304
TI  - Genetic basis of inherited peripheral neuropathies.
AB  - Progress in the elucidation of the genetic basis for inherited peripheral
      neuropathies has been remarkable over the last years. In particular, the
      molecular mechanisms underlying the autosomal dominantly inherited disorders
      Charcot-Marie-Tooth disease type 1A (CMT1A), Charcot-Marie-Tooth disease type 1B
      (CMT1B), and hereditary neuropathy with liability to pressure palsies (HNPP) have
      been determined. While mutation in the gene encoding the major myelin protein, P0
      has been associated with CMT1B, CMT1A and HNPP have been shown to be associated
      with reciprocal recombination events leading either to a large submicroscopic
      duplication in CMT1A, or the corresponding DNA deletion in HNPP. Available
      evidence is consistent with the hypothesis that one or more genes within the
      relevant rearranged segment of 1.5 Mb on chromosome 17 is sensitive to gene
      dosage providing a novel mechanism for inherited human disorders. It is likely
      that the gene encoding the peripheral myelin protein PMP22 is at least one of the
      genes involved since the PMP22 gene maps within the CMT1A duplication (or HNPP
      deletion), and point mutations within it have been shown to cause a CMT phenotype
      in humans and comparable neuropathies in rodents (trembler and tremblerJ). The
      mechanism(s) by which gene dosage and point mutations affecting the same gene
      might lead to a similar phenotype are currently unknown but recent transgenic
      mouse experiments suggest that similar mechanisms may also underlie other genetic
      diseases.

PMID- 7515305
TI  - [Prostate-specific antigen: an evaluation 15 years after its discovery].
AB  - Fifteen years after its discovery, PSA is the most useful marker for prostate
      cancer. We summarize the biomolecular characteristics of PSA and the various PSA
      assays. We define its role in the diagnosis of prostate cancer, and we discuss
      its value in the monitoring of treated patients.

PMID- 7515306
TI  - Cryptosporidiosis associated with farm visits.

PMID- 7515307
TI  - Regulation of asialoglycoprotein receptor synthesis by inflammation-related
      cytokines in HepG2 cells.
AB  - The asialoglycoprotein receptor (AGPR) is responsible for the catabolism of acute
      phase proteins. The effects of inflammation-related cytokines on the expression
      of AGPR were investigated in HepG2 cells derived from a human hepatoblastoma cell
      line. Binding studies, using a [125I]-labeled asialo-orosomucoid ligand, revealed
      that AGPR numbers on cell surfaces were increased by interleukin-1 (IL-1),
      interleukin-6 (IL-6), and tumor necrosis factor (TNF). In cells treated with IL
      1, IL-6, or TNF, immunohistochemical staining with an anti-AGPR monoclonal
      antibody demonstrated augmented expression. Pulse labeling analysis, using [35S]
      labeled methionine, showed newly synthesized AGPR in both the precursor and the
      mature forms. When IL-1, IL-6, and TNF were added to the culture medium, total
      synthesis of AGPR (sum of the mature and precursor forms) was increased. In
      addition, the relative proportion of the synthesized precursor form of AGPR was
      higher in cytokine-treated than in untreated cells, suggesting that these
      cytokines augment the synthesis of AGPR, particularly in the stage prior to
      glycosylation.

PMID- 7515308
TI  - Alpha-fetoprotein-producing early gastric cancer accompanying liver cirrhosis: a
      case report.
AB  - A rare case of alpha-fetoprotein (AFP)-producing early gastric cancer with liver
      cirrhosis is presented. A 61-year-old man was admitted to Shimane Medical
      University Hospital in 1988 because of abnormal liver function test results
      suggestive of liver cirrhosis with mild elevation of AFP. Liver cirrhosis was
      confirmed laparoscopically and histologically. Gastric cancer was found in
      fluoroscopic and endoscopic studies. After partial gastrectomy, the serum AFP
      level fluctuated transiently within normal limits, and then gradually increased
      soon after the operation. Therefore, complication of hepatocellular carcinoma was
      suspected, but no tumor in the liver was detected by any imaging examination,
      including angiography. Two years after the operation, swelling of abdominal
      periaortic lymph nodes was noted at a periodic checkup, but still no hepatic
      tumor was found. At this point, AFP-producing gastric cancer was suspected, and
      an AFP staining test was carried out on the tissue of the resected specimen. AFP
      positive cells were recognized immunohistochemically. Thus, we diagnosed the
      condition as post-operative recurrence of an AFP-producing gastric cancer
      accompanying liver cirrhosis.

PMID- 7515309
TI  - A case of appendiceal cancer metastatic to the stomach with pseudomyxoma
      peritonei.
AB  - Appendiceal cancer associated with pseudomyxoma peritonei is a low grade
      malignancy and its extraperitoneal metastasis is extremely rare. We report a case
      of gastric metastasis of this tumor in a 76-year-old man. Two metastatic gastric
      tumors, which appeared after a 1-year interval, were successfully resected
      endoscopically. The patient was well for more than 3 years after the onset of the
      disease. To our knowledge, gastric metastasis from appendiceal cancer with
      pseudomyxoma peritonei has not been previously reported.

PMID- 7515310
TI  - Monoaminergic neuronal activity in subcortical brain regions in essential
      hypertension.
AB  - In this study we aimed to elucidate the role of central noradrenergic,
      dopaminergic, adrenergic and serotonergic neuronal systems in the development of
      essential hypertension. Fifteen untreated essential hypertensive subjects (aged
      44 +/- 3 years) and 32 healthy volunteers (aged 38 +/- 3 years) participated in
      this study. By combining direct blood sampling techniques with cerebral blood
      flow scans we were able to differentiate between cortical and subcortical venous
      drainage of the brain. Veno-arterial MHPG, HVA and 5-HIAA plasma concentration
      gradients combined with internal jugular vein plasma flows were used, according
      to the Fick Principle, to derive metabolite spillovers which in turn were used as
      indicators of central noradrenergic, dopaminergic and serotonergic neuronal
      activity, respectively. These amine systems, in both the brainstem and forebrain,
      have been implicated in the regulation of sympathetic outflow and blood pressure.
      Total body noradrenaline spillover to plasma was concurrently measured to assess
      the relationship between central monoamine turnover and sympathetic activity.
      Compared to their healthy counterparts the hypertensive subjects had an elevated
      release of MHPG from subcortical brain regions (1.4 +/- 0.3 v 0.5 +/- 0.2
      nmol/min, p < 0.05). An inverse relationship between blood pressure and
      subcortical HVA overflow existed, with the HVA overflow being significantly lower
      in the hypertensives (0.5 +/- 0.2 v 2.1 +/- 0.5 nmol/min, p < 0.05). Subcortical
      5-HUAA overflow did not differ between the two groups, and adrenaline spillover
      from the brain was not detected in either group. Subcortical MHPG overflow was
      significantly correlated with total body NA spillover to plasma (p < 0.05). These
      results indicate that reciprocal aberrations in subcortical noradrenaline and
      dopamine turnover exist in essential hypertension. Although the physiological
      significance of this remains to be unequivocally elucidated we postulate that
      elevated subcortical noradrenergic activity, presumably in the forebrain where
      noradrenergic neurons are pressor, may cause sympathoexcitation and play a role
      in the development of essential hypertension.

PMID- 7515311
TI  - The expression and localisation of the angiotensin-converting enzyme mRNA in
      human adipose tissue.
AB  - Recent evidence in rats has indicated that angiotensinogen may be synthesised in
      adipose tissue surrounding blood vessels and that a local renin-angiotensin
      system may regulate adipose tissue blood supply and the efflux of fatty acids
      from fat in that species. This hypothesis is critically dependent on the local
      expression of the angiotensin converting enzyme gene in adipocytes. Thus the
      current study set out to examine whether the angiotensin converting enzyme gene
      was expressed in human adipose tissue and, if it was present, to localise the
      individual sites of that expression. Northern analysis indicated the presence of
      mRNA for angiotensin converting enzyme in both subcutaneous and extraperitoneal
      adipose tissue. In situ hybridisation showed that the gene was expressed in
      adipocytes. The foregoing results therefore suggest that components of the renin
      angiotensin cascade are also present in human adipose tissue and support the
      hypothesis that adipose tissue may play a role in the local production of
      Angiotensin II and hence participate in vascular function and blood pressure
      control in the human.

PMID- 7515312
TI  - Lipoprotein receptors in arterial tissue: relation to the pathology of
      atherosclerosis.
AB  - The molecular and cellular physiology of several classes of lipoprotein receptors
      has been extensively characterized in vitro. However, the evidence that these
      lipoprotein receptors mediate the morphological events characteristic of
      atherosclerotic development in vivo is limited. The increasing availability of
      reagents to characterize receptor mRNA and protein will enable the definition of
      receptors involved in atherosclerotic lesion progression. These studies should
      set the stage for the more difficult task of modulating lipoprotein receptors to
      determine whether their activity is a critical component of atherogenesis.

PMID- 7515314
TI  - The effects of KB-2796 and BAY K 8644 on fentanyl-induced analgesia in rats.
AB  - We investigate the modulatory effects of subcutaneous administration of different
      doses of KB-2796 (1, 5 and 15 mg/kg), a new calcium channel blocker, and BAY K
      8644 (0.25, 0.5 and 1 mg/kg), a calcium agonist, on fentanyl-induced analgesia
      (20 micrograms/kg) in rats. The drugs were tested individually as well as in
      combination with fentanyl. Dimethyl sulfoxide (DMSO) was used as a control.
      Nociceptive sensitivity was assessed by the tail-flick technique. When KB-2796
      and BAY K 8644 were used alone, only KB-2796 at the dose of 15 mg/kg produced an
      effect that was significantly different from that of DMSO (p < 0.01). The effect
      was antinociceptive. When administered with fentanyl, KB-2796 at 5 and 15 mg/kg
      potentiated the analgesic effect of fentanyl (p < 0.05), but suppression of
      fentanyl analgesia by BAY K 8644 was not significant at any of the doses tested.
      Our data supports the hypothesis that the calcium ion is partially involved in
      fentanyl-induced analgesia.

PMID- 7515313
TI  - Intercellular localization of acid invertase in tomato fruit and molecular
      cloning of a cDNA for the enzyme.
AB  - The localization of acid invertase (AI, EC 3.2.1.26) in tomato fruits was
      studied. AI was localized in the intercellular fraction (cell wall fraction). A
      cDNA encoding a wall-bound form of AI from tomato fruits was cloned and its
      nucleotide sequence was determined. The cloned cDNA was 2363 base pairs long and
      contained an open reading frame of 1908 base pairs which encoded a polypeptide of
      636 amino acids. RNA blot analysis indicated that the mRNA for the acid invertase
      was about 2.5 kb in length. The levels of the mRNA were low at the mature green
      stage but increased during ripening of fruit.

PMID- 7515315
TI  - Shoulder pain due to rupture of a calyceal diverticulum as an acute sign of
      prostatic hyperplasia.

PMID- 7515316
TI  - Zonal organization of climbing fiber projections to the nodulus in the cat.
AB  - Climbing fiber projections from the inferior olive to the nodulus of the
      cerebellum were studied by means of the retrograde transport of horseradish
      peroxidase in the cat. Following large and small injections into various parts of
      the nodulus, the distribution of labeled cells in the inferior olive was
      investigated. The findings indicate the existence of five longitudinal zones
      extending throughout the dorsal and ventral nodulus: (1) the caudal part of the
      nucleus beta projects to a most medially located zone (caudal beta zone) with a
      width of about 0.6 mm; (2) the rostral part of the nucleus beta projects to a
      zone located at 0.6-1.2 mm from the midline (rostral beta zone); (3) the caudal
      part of the dorsal cap (dc) projects to a zone located in the intermediate part
      of the nodulus at 1.2-1.8 mm from the midline (caudal dc zone); (4) the
      ventrolateral outgrowth (vlo) of the dc and the rostral part of the dc project to
      a zone at 0.3-0.9 mm from the lateral edge of the nodulus (rostral dc and vlo
      zone); and (5) finally the dorsomedial cell column (dmcc) projects to the most
      lateral zone (dmcc zone).

PMID- 7515317
TI  - Mossy fiber projections from the brain stem to the nodulus in the cat. An
      experimental study comparing the nodulus, the uvula and the flocculus.
AB  - Mossy fiber projections from the brainstem to the nodulus were studied by means
      of the retrograde transport of horseradish peroxidase (HRP) in the cat. The
      findings indicate exclusive secondary vestibular projections to the nodulus
      (96.5% of the total number of labeled cells in cat 1). Major sources of such
      projections include the caudal half of the medial and inferior vestibular nuclei,
      and the dorsal half of the superior vestibular nucleus. Groups-x and -z of the
      vestibular nuclei give rise to minor projections. The projections from groups-f
      and -y, and the interstitial nucleus of the eighth nerve are very few, if any.
      Minor extravestibular projections originate from the prepositus hypoglossal
      nucleus and the infratrigeminal nucleus. All these projections are bilateral. No
      other nuclei in the brainstem were labeled following HRP injection in the
      nodulus. No indications of mediolateral and dorsoventral differences in mossy
      fiber projections were found. There are quantitative differences in the sources
      of projections to the nodulus, the ventral uvula and the flocculus, all of which
      belong to the vestibulocerebellum. The largest sources for projections to the
      nodulus and the ventral uvula are from the vestibular nuclei. Among the
      vestibular nuclei, group-x provides the major projections to the ventral uvula.
      For the flocculus, in contrast, the major sources of input are the reticular
      formation and raphe nuclei. These quantitative differences may play an important
      role for differential functions of the nodulus, the ventral uvula and the
      flocculus.

PMID- 7515320
TI  - Substance P-like immunoreactivity in the hypothalamic suprachiasmatic nucleus of
      Phodopus sungorus--relation to daytime, photoperiod, sex and age.
AB  - The immunohistochemical distribution of substance P (SP) in the hypothalamic
      suprachiasmatic nucleus (SCN) was studied in adult male and female Djungarian
      hamsters (Phodopus sungorus) held under either long or short photoperiods. Intact
      animals were killed by perfusion with a fixative at the middle of the light or
      dark periods, respectively. The tissue was processed by routine
      immunohistochemical methods. Perikarya exhibiting SP-like immunoreactivity (LI)
      were found in the SCN of animals of all groups. These cell bodies predominantly
      were restricted to a distinct portion of the nucleus extending less than 150
      microns rostrocaudally and were often concentrated in its lateral aspect. SP-LI
      fibers were rarely observed in the SCN, however, other hypothalamic parts, e.g.
      anterior and paraventricular regions, exhibit strong SP-LI innervation patterns.
      Sex-related differences were not observed. Long-term exposure to short days
      decreased the number of neurons exhibiting SP-LI by approximately 60% when
      compared to long-day animals at both day- and nighttime. At night, SP-LI neurons
      were augmented in number by 34% (long-day group) and 56% (short-day group).
      Further, the numbers of SP-LI perikarya in the SCN of aged hamsters at day- and
      nighttime were augmented 3- to 4-fold when compared to adult animals. These
      results suggest that substance P in the SCN is involved in the regulation of
      circadian and seasonal mechanisms in this highly photoperiodic rodent species.

PMID- 7515319
TI  - Collateral axonal projections to limbic structures from ventrolateral medullary
      A1 noradrenergic neurons.
AB  - Experiments were done to investigate whether catecholaminergic neurons within the
      ventrolateral medulla (VLM) send collateral axonal projections to the central
      nucleus of the amygdala (ACe) and the bed nucleus of the stria terminalis (BST).
      Unilateral microinjections of the fluorescent retrograde tracers fluorogold (FG)
      or rhodamine labelled latex micro-beads (Rd) were made into either ACe or BST in
      the rat. Brainstem sections were then processed immunohistochemically for the
      identification of cell bodies containing the catecholamine biosynthetic enzymes
      tyrosine hydroxylase, dopamine beta-hydroxylase (DBH) or phenylethanolamine-N
      methyltransferase (PNMT). Retrogradely labelled cell bodies projecting to either
      ACe or BST were found throughout the rostrocaudal extent of VLM, bilaterally.
      Approximately 44% of these retrogradely labelled neurons were found to contain
      both retrograde tracers. In addition, approximately 91% of the VLM neurons that
      send collateral axonal projections to ACe and BST were also immunoreactive to
      DBH. None were found to contain PNMT immunoreactivity. These results demonstrate
      that noradrenergic neurons of the A1 cell group in VLM innervate ACe and BST via
      collateral axonal projections and suggest that these VLM neurons may be directly
      involved in relaying cardiovascular afferent and/or visceral afferent information
      directly to these limbic structures.

PMID- 7515318
TI  - Distribution of glutamate- and GABA-immunoreactive neurons projecting to the
      cardioacceleratory center of the intermediolateral nucleus of the thoracic cord
      of SHR and WKY rats: a double-labeling study.
AB  - We aimed at (1) determining the distribution of glutamate (Glu)- and gamma
      aminobutyric acid (GABA)-containing neurons in the brainstem with projections to
      the cardioacceleratory sympathetic preganglionic neurons in the intermediolateral
      nucleus (IML) of the upper thoracic cord and (2) determining whether such
      afferent projections in spontaneously hypertensive rats (SHR) differ from those
      of control Wistar-Kyoto (WKY) rats. We used a combination of electrophysiological
      methods to determine the site of HRP injection in the spinal cord and double
      labeling methods for plotting the distribution of Glu- and GABA-immunoreactive
      neurons with projections to this site. HRP/Glu-labeled neurons (possibly
      glutamatergic) and HRP/GABA-labeled neurons (possibly GABAergic) were detected in
      27% and 7% of the total HRP-labeled neurons of the central autonomic nuclei of 3
      SHR rats and 3 WKY rats. HRP/Glu-labeled neurons were distributed predominantly
      ipsilaterally in 20 nuclei of the medulla oblongata, pons and hypothalamus, while
      HRP/GABA-labeled neurons were distributed in 7 nuclei of the medulla oblongata.
      No significant differences were found between the average percentages of HRP/Glu
      labeled and HRP/GABA-labeled neurons in SHR and WKY rats. These findings indicate
      that: (1) the Glu-containing neurons represent a greater proportion than the GABA
      containing neurons, (2) the proportions of these neurons appear to be similar in
      WKY and SHR rats and (3) generation of inbred tachycardia and hypertension in SHR
      rats can not be attributed to the topological and quantitative differences in the
      distribution of the glutamatergic and GABAergic neurons in the central autonomic
      nuclei.

PMID- 7515321
TI  - Substance P suppresses the activity of alpha 2-adrenoceptors of the nucleus
      reticularis gigantocellularis involved in cardiovascular regulation in the rat.
AB  - We evaluated possible interactions between substance P (SP) and the alpha 2
      adrenoceptors in the nucleus reticularis gigantocellularis (NRGC) of the medulla
      oblongata involved in cardiovascular regulation. Adult, male Sprague-Dawley rats
      anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v.
      supplements) were used. The circulatory suppressant efficacy of a centrally
      acting alpha 2-adrenoceptor agonist, guanabenz, was used as the experimental
      index. Bilateral microinjection of SP (300 or 600 pmol) into the NRGC, a
      medullary site that is critically involved in the cardiovascular depressive
      actions of guanabenz, significantly diminished the hypotensive and bradycardiac
      efficacy of the aminoguanidine compound (100 micrograms/kg, i.v.). This implied
      reduction in alpha 2-adrenoceptor activity in the NRGC by SP was antagonized by
      its selective receptor antagonist, [D-Pro2,D-Trp7,9]-SP (1200 pmol). Similarly,
      attenuation by SP of the cardiovascular suppressant effects of guanabenz was also
      reversed by immunocytochemically verified depletion of dopamine-beta-hydroxylase
      immunoreactive nerve terminals in the NRGC, elicited by the selective
      noradrenergic neurotoxin, DSP4 (50 micrograms). These data suggest that SP may
      exert an inhibitory action on the alpha 2-adrenoceptors in the NRGC that are
      involved in central cardiovascular regulation, possibly via a presynaptic
      modulation on noradrenergic neurotransmission.

PMID- 7515322
TI  - CNS monoamine cell groups projecting to pancreatic vagal motor neurons: a
      transneuronal labeling study using pseudorabies virus.
AB  - The CNS monoamine cell groups that project to the pancreatic parasympathetic
      preganglionic neurons were identified with the use of the viral retrograde
      transneuronal labeling method. Pseudorabies virus (PRV) was injected into the
      pancreas of C8 spinal rats and subsequently, transneuronally-labelled central
      monoamine neurons were mapped in brain tissue sections that had been stained by
      an immunohistochemical procedure that allowed for the visualization of PRV
      products and biogenic amine neurotransmitter enzymes or serotonin (5-HT) in the
      same neuron. The enzymes studied were tyrosine hydroxylase (TH), dopamine-beta
      hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT), and histidine
      decarboxylase. Pancreatic vagal motor neurons originate exclusively from the
      dorsal vagal motor nucleus and some of these may be dopamine neurons because they
      were TH immunopositive, but DBH and PNMT immunonegative. Transneuronally labeled
      aminergic neurons were found throughout the medulla oblongata. The adrenergic
      inputs arose from the C1, C2, and C3 cell groups. Noradrenergic inputs originated
      predominantly from the A5 cell group, with lesser contributions from the A1 and
      A2 cell groups as well as from the area postrema. None of the other CNS
      catecholamine cells were labeled, except for some weakly staining TH
      immunoreactive neurons, presumably dopaminergic, in the paraventricular
      hypothalamic nucleus (PVN). The greatest number of 5-HT neurons that innervate
      the pancreatic vagal motor neurons come from the gigantocellular reticular
      nucleus, pars alpha with lesser inputs from the raphe magnus, obscurus, and
      pallidus nuclei. None of the CNS histaminergic cell groups were labeled.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7515324
TI  - Alterations in acetylcholinesterase and choline acetyltransferase activities and
      neuropeptide levels in the ventral spinal cord of the Wobbler mouse during
      inherited motoneuron disease.
AB  - Enzymatic assays for acetylcholine esterase (AChE) and choline acetyltransferase
      (ChAT) were applied to dorsal and ventral cervical spinal cord regions taken from
      the Wobbler mouse, a model for inherited motoneuron disease. Early in the
      disease, ChAT (but not AChE) activity is significantly greater compared with the
      control littermate specimens. The high ChAT activity correlates with the high
      thyrotropin releasing hormone (also leucine-enkephalin) concentrations measured
      in the Wobbler ventral horn early in the disease. Late in the motoneuron disease,
      both AChE and ChAT activities are significantly lower than in the control
      littermate specimens. These data correlate with the high substance P, methionine
      and leucine enkephalin concentrations measured in the Wobbler ventral horn late
      in the motoneuron disease.

PMID- 7515323
TI  - Enhancement of cytosolic calcium, prostacyclin and nitric oxide by bradykinin and
      the ACE inhibitor ramiprilat in porcine brain capillary endothelial cells.
AB  - We studied whether primary cultured porcine brain capillary endothelial cells
      (PBCEC) respond to bradykinin with an enhanced intracellular cytosolic calcium
      concentration [Ca2+]i with subsequent formation of nitric oxide (NO) and
      prostacyclin (PGI2). In addition we examined whether these cells synthetize and
      release kinins that may accumulate during angiotensin-converting enzyme (ACE)
      inhibition. [Ca2+]i was assessed by the fluorescent dye Fura-2, NO formation by
      determination of intracellular cyclic GMP and PGI2 by a specific radioimmunoassay
      for 6-ketoprostaglandin F1 alpha. Bradykinin and the ACE inhibitor ramiprilat
      concentration-dependently increased the formation of cyclic GMP which was
      completely prevented by the stereospecific inhibitor of NO synthase, NG-nitro-L
      arginine. Also the specific B2-kinin receptor antagonist icatibant (Hoe 140)
      abolished the increase in cyclic GMP as well as the ramiprilat-induced increase
      in PGI2 formation. The data demonstrate the existence of B2-kinin receptors and
      ACE activity in PBCEC. Moreover PBCEC are capable of producing and releasing
      kinins in amounts that lead via stimulation of B2-kinin receptors to an enhanced
      [Ca2+]i as well as NO and PGI2 synthesis and release, provided that degradation
      of kinins is prevented by inhibition of endothelial ACE activity.

PMID- 7515325
TI  - The effect of racemic ketamine on the large conductance Ca(+2)-activated
      potassium (BK) channels in GH3 cells.
AB  - Recently, inhalation anesthetics have been reported to block BK channels in
      adrenal chromaffin cells. To determine if BK block was characteristic only of
      inhalation anesthetics or was also a property of other general anesthetics we
      examined the effects of ketamine, an intravenous general anesthetic which is
      structurally different than inhalation anesthetics. Cell-attached and excised
      patch single channel and standard whole cell recording techniques were used to
      examine the effect of racemic ketamine on the BK channel activity in GH3 cells.
      When solutions containing 150 mM KCl are used in both the pipette and bath, the
      BK channels are characterized as a voltage-dependent channel with a unit
      conductance of 150-300 pS. Racemic ketamine (at clinically relevant
      concentrations; 2-500 microM) selectively blocked BK channels in a dose
      dependent, reversible manner as evidenced by decreases in NPo (number of channels
      x open probability). This decrease was due to both a decrease in mean open time
      and an increase in the mean closed time but without a decrease in single-channel
      current amplitude. Ketamine shifts the Po vs voltage curve to higher potentials
      without a change in the slope of the voltage dependence. Ketamine also shifts the
      Po vs [Ca+2] relationship to higher Ca+2 concentrations. The IC50 for the single
      channel block by ketamine is 20.3 +/- 15.9 microM. In an effort to confirm that
      the effect of ketamine was predominantly due to a block of the BK channels,
      standard whole cell techniques were utilized.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515327
TI  - Increased numbers of argyrophilic nucleolar organizer regions between primary and
      metastatic sites predict tumor progression in stage IV and IV-S neuroblastoma.
AB  - BACKGROUND: A silver colloid technique to determine nucleolar organizer region
      (AgNOR) number was used to study the proliferative activity of Stage IV-S
      neuroblastoma in which a spontaneous tumor regression is often observed. METHODS:
      Primary regional lymph nodes and hepatic lesions from five children with Stage IV
      S and five with Stage IV neuroblastoma were examined. RESULTS: Average AgNOR
      counts per tumor cell nucleus from all five children with Stage IV neuroblastoma
      were lowest in the primary lesions, intermediate in the metastatic regional lymph
      nodes, and highest in the distant metastases. However, in four Stage IV-S
      patients whose metastases later disappeared and showed no sign of recurrence, the
      average AgNOR number was similar in primary tumors and metastatic lesions. In the
      other patient with progressive metastases initially diagnosed as Stage IV-S, the
      data showed the same pattern as in Stage IV neuroblastoma. CONCLUSIONS: The
      unique AgNOR staining pattern may reflect the proliferative activity of Stage IV
      S neuroblastoma. This method may provide further information to differentiate a
      subtype of metastatic neuroblastoma showing spontaneous tumor regression and/or
      favorable prognosis.

PMID- 7515328
TI  - Function of the peripheral serotoninergic pathways in migraine: a proposal for an
      experimental model.
AB  - We propose a model for assessing the function of 5HT receptors in migraine by
      evaluating their expression on monocytes by means of double-labeling
      fluorocytometry (CD14-positive cells FITC-labeled). This model demonstrates that
      during headache induced in migraine without aura sufferers given isosorbide
      dinitrate followed by sumatriptan treatment 5HT expression on monocytes
      progressively increases. This increase may be due to the activation of 5HT
      turnover and to the increased availability of 5HT displaced by sumatriptan from
      cerebrovascular receptors during head pain.

PMID- 7515326
TI  - Epstein-Barr virus positivity in Hodgkin's disease does not correlate with an HLA
      A2-negative phenotype.
AB  - BACKGROUND: Epstein-Barr virus- (EBV) related DNA and RNA can be found in tissues
      involved with Hodgkin's disease, specifically in the Reed-Sternberg cells. These
      cells also express the membrane antigens LMP1 and LMP 2A and 2B. Studies in
      normal individuals indicate that cellular immunity against LMP2 was frequently
      mediated through human leukocyte antigen (HLA) A2, whereas responses to LMP1
      appeared to be relatively infrequent. Assuming that LMP2-positive Reed-Sternberg
      cells would be sensitive to a CD8-positive cellular immune response, the
      hypothesis can be made that EBV-positive Hodgkin's disease should be more common
      in individuals not expressing HLA A2. To test this hypothesis, the authors have
      studied the frequency of HLA A2 in EBV-positive versus EBV-negative patients with
      Hodgkin's disease. METHODS: All 72 patients diagnosed with Hodgkin's disease in
      Northern and Central Alberta, Canada, during 1990 and 1991 were studied. A
      nonisotopic in situ hybridization method with an oligonucleotide probe specific
      for EBER 1 and 2 was used. In addition, sections were stained for the EBV-latent
      protein LMP1, HLA A2, and a monomorphic HLA class I determinant and beta 2
      microglobulin. RESULTS: EBER-positive Reed-Sternberg cells were found in 26% of
      the patients. The percentage of positive patients was 86% in mixed cellularity,
      13% in nodular sclerosis, and 0% in lymphocyte predominance. The number of those
      who were HLA-A2 positive was approximately 50% in the EBV-positive and -negative
      patients. CONCLUSIONS: Therefore, no correlation between HLA A2 expression and
      presence or absence of EBV in the R-S cells of Hodgkin's disease was identified.

PMID- 7515329
TI  - Absence of vasoactive peptide release from brain to cerebral circulation during
      onset of migraine with aura.
AB  - In eight patients carotid angiography was required for evaluation of transient
      neurological attacks. Cerebral blood flow results, angiography and clinical
      observations subsequently suggested the diagnosis of migraine. We measured plasma
      concentrations of substance P(SP), neuropeptide Y (NPY), calcitonin gene-related
      peptide (CGRP) and vasoactive intestinal peptide (VIP) in repeated blood samples
      obtained from the carotid artery and the internal jugular vein in conjunction
      with cerebral angiography followed by 4 to 6 repeated recordings of regional
      cerebral blood flow (rCBF) with the intracarotid Xenon-133 injection technique.
      This technique is known to induce attacks of migraine with aura in many
      sufferers. Four patients developed aura symptoms. In three this was succeeded by
      throbbing headache. Typical, migraine-related, focal hypoperfusion occurred in
      conjunction with the aura symptoms. The remaining four patients had no symptoms
      or rCBF changes. There were no systematic or statistically significant changes
      over time in arterial-venous plasma concentrations or in the release rates of any
      of the peptides. All migraineurs had an overall elevated mean CGRP value compared
      to control values from the literature. The overall plasma levels of the potent
      vasoconstrictor NPY were higher (p < 0.10) in the group that developed symptoms
      and rCBF changes (136 pmol/l) than in the non-symptomatic group (97 pmol/l). The
      difference in NPY levels could perhaps be associated with the focal rCBF decrease
      seen in the attack group.

PMID- 7515330
TI  - Regulation of experimental autoimmune neuritis by transforming growth factor-beta
      1.
AB  - Experimental autoimmune neuritis (EAN) is a T-cell-mediated autoimmune disease
      characterized by demyelination and mononuclear cell infiltration of the
      peripheral nervous system. It is induced in Lewis rats by administration of
      myelin P2 protein or a synthetic peptide (SP-26) corresponding to amino acid
      residues 53-78 of bovine P2 protein. The effects of transforming growth factor
      beta 1 (TGF-beta 1) on the clinical signs, histological changes, cell-mediated
      immune responses, and secretion of interferon-gamma (IFN-gamma) by lymphoid cells
      of rats with EAN were examined. Systemic administration of TGF-beta 1 markedly
      inhibited the clinical signs and histological changes of EAN when given
      intraperitoneally every other day for Days 0 through 18. In addition, it
      decreased proliferative responses and reduced the delayed-type hypersensitivity
      (DTH) response to SP-26 compared to control rats. The reduction in clinical
      severity correlated with skin test unresponsiveness (DTH) to the disease-inducing
      agent (SP-26) as well to decreased cellular responsiveness to the antigen in
      vitro. The decrease in cellular responsiveness extended to a decrease in at least
      one T cell lymphokine, IFN-gamma. The profound effect of TGF-beta on disease
      progression in EAN, a T-cell-mediated process, is consistent with a direct effect
      of this growth factor on T lymphocytes.

PMID- 7515331
TI  - Costimulation of superantigen-activated T lymphocytes by autologous dendritic
      cells is dependent on B7.
AB  - Highly purified populations of dendritic cells (DCs) can be isolated from various
      tissues such as skin and blood. These sites are likely to encounter secreted
      toxins of bacteria such as superantigens. In vivo, DCs express the cell surface
      molecule B7, a counterreceptor for CD28 which provides costimulation to resting T
      cells. Highly purified preparations of DCs obtained from the epidermis and dermis
      of normal skin as well as blood were used to study the role of B7 in superantigen
      presentation to autologous T cells, as well as in alloantigen responses. We
      compared these results to those obtained with nondendritic antigen presenting
      cells (APCs) such as mononuclear cells derived from the Ficoll-Hypaque interface
      (PBMCs). All DC populations strongly express B7, and in a purely autologous
      system staphylococcal enterotoxin B (SEB)-mediated T cell proliferation was
      inhibited by 55-85% using a soluble chimeric fusion protein (i.e., CTLA4Ig), a
      potent inhibitor of CD28:B7 interaction. In contrast, while T cells also
      proliferated vigorously when stimulated by SEB in the presence of autologous PBMC
      (which only weakly express B7), costimulation was not inhibited by CTLA4Ig. In
      allogeneic responses, DCs were also more potent stimulators compared to PBMC, but
      both types of APC:T cell reactions were almost completely inhibited by CTLA4Ig (>
      90%). For both SEB-mediated reactions and alloantigen reactions, the relative
      importance of LFA-1 and HLA-DR was similar between DCs and PBMCs. The data
      indicate that these DCs express B7, which can function in the SEB-driven response
      of autologous T cells, as well as in allogeneic T cell reactions. Overall, when
      comparing the relative costimulatory capabilities of different types of APCs, it
      appears the relatively low level of B7 expressed by PBMC functioned effectively
      in allogeneic reactions, whereas only the higher levels of B7 expressed by these
      DC populations functioned in SEB-mediated T cell responses.

PMID- 7515334
TI  - Cross-reactivity to proteoglycans in bacterial arthritis: lack of evidence for in
      vivo role in induction of disease.
AB  - Cross-reactivity between bacterial epitopes and cartilage components has been
      assumed to play a role in the pathology of bacterial-induced arthritis models. In
      this study, we report prominent proteoglycan (PG) depletion in Safranin-O stained
      ankle joint sections from collagen-induced arthritic rats. In adjuvant arthritis
      and streptococcal cell wall-induced arthritis (SCW-A), however, only limited PG
      degradation was observed. In vitro, PG fractions were able to stimulate T
      lymphocytes from these arthritic rats. To investigate the contribution of cross
      reactivity, Lewis rats were primed with SCW in Freund's incomplete adjuvant
      (SCW/FIA). This immunization protocol resulted in in vitro stimulatory responses
      to the SCW antigens and cartilage PG antigens, but not to joint inflammation per
      se. Next, papain was injected intraarticularly to create a situation in which a
      large amount of potential cross-reactive cartilage epitopes are released.
      Interestingly, no inflammatory reaction could be observed in the papain-injected
      joints of SCW/FIA-primed rats. These data suggest that cross-reactivity between
      bacterial epitopes and PG does not seem to be a key element in the onset of joint
      inflammation in bacterial-induced arthritis. However, it cannot be ruled out that
      at later time points cross-reactivity will contribute to joint inflammation.

PMID- 7515333
TI  - Interindividual difference in expression of human Ah receptor and related P450
      genes.
AB  - The genomic clones of human aryl hydrocarbon receptor (Ahr) and Ahr nuclear
      translocator (Arnt) were isolated, and the structures of exon-intron junctions of
      these genes were partially determined. Based on the sequence information, a
      quantitative RT-PCR analysis was developed, and the expression of these genes was
      studied in various human tissues. mRNAs for Ahr and Arnt were widely expressed in
      human tissues and abundantly in lung. Individual difference in expression levels
      of Ahr and Arnt mRNA was observed in liver, lung and blood. In order to examine
      whether expression levels of Ahr and Arnt were associated with those of CYP1A1,
      we studied the expression of these mRNAs in blood among 20 healthy subjects,
      taking account of individuals' cigarette smoking habits. We found that the
      expression levels of CYP1A1 appeared to associate with those of Ahr and Arnt
      mRNAs (P < 0.06), and also that the expression of Ahr and Arnt was influenced by
      cigarette smoking. The expression of human Ahr and Arnt is reported here for the
      first time, providing a quantitative RT-PCR analysis as a useful tool for further
      studies.

PMID- 7515332
TI  - Lewis rat T cells can reutilize, process, and present myelin basic protein to
      antigen-specific T cell lines.
AB  - MHC class-II-negative astrocytes prevented from intracellular antigen (Ag)
      processing induce myelin basic protein (MBP)-specific short-term T cell lines to
      proliferate. This process results from the ability of the T cells themselves to
      take up, process, and present Ag to each other. The Ag-presenting function of the
      T cells occurred in the absence of any conventional antigen-presenting cell
      (APC), was independent of their T cell receptor specificity, was sensitive to
      chloroquine, and was prevented by anti-class-II MHC antibody. Both native and
      HPLC-purified MBP were effective in stimulating T cell lines, and there was no
      obvious benefit in using either enzymatically digested or synthetic peptide
      preparations of the Ag. Furthermore, the Ag-presenting T cells could take up,
      reutilize, and re-present Ag adsorbed to the surface of histoincompatible
      astrocytes. Responding T cells activated by Ag-presenting T cells in the absence
      of other conventional APC were fully encephalitogenic upon transfer to syngeneic
      recipients. These results have relevance for understanding pathogenetic
      mechanisms in T cell-mediated autoimmunity in the central nervous system.

PMID- 7515335
TI  - Intravascular neutrophil activation in systemic lupus erythematosus (SLE):
      dissociation between increased expression of CD11b/CD18 and diminished expression
      of L-selectin on neutrophils from patients with active SLE.
AB  - Previous studies have shown that neutrophils in the circulation of patients with
      active systemic lupus erythematosus (SLE) are activated as judged by their
      increased surface expression of the beta 2-integrin CD11b/CD18. Since activation
      of neutrophils leads to altered expression of another adhesion molecule, L
      selectin (LS), we examined neutrophils from patients with SLE for changes in the
      expression of CD11b/CD18 and LS by cytofluorographic analysis of
      immunofluorescent-labeled cells. Overall there was no difference between surface
      expression of CD11b/CD18 on neutrophils from SLE patients or controls [mean
      fluorescence 225 +/- 26 vs 225 +/- 13 relative fluorescence units (RFU),
      respectively]. However, as previously reported, neutrophils from patients with
      more active disease (activity score > or = 3, UCH Middlesex activity score)
      expressed greater CD11b/CD18 than neutrophils from controls (319 +/- 40 RFU, P <
      0.03, n = 9) or from patients with less active disease (193 +/- 10 RFU, P <
      0.006). Indeed, CD11b/CD18 expression correlated directly with disease activity
      (r = 0.54, P < 0.02). Stimulation of neutrophils ex vivo with the chemoattractant
      N-formyl-methionyl-leucyl-phenylalanine (100 nM) induced up-regulation of
      CD11b/CD18 in cells from both SLE patients and controls (205 +/- 12% vs 239 +/-
      15% of basal, respectively), but neutrophils from the most active patients (score
      > or = 3) increased CD11b/CD18 expression less than controls (175 +/- 12% of
      basal, P < 0.003, n = 9). The magnitude of the stimulated increment in expression
      of CD11b/CD18 on neutrophils correlated inversely with SLE activity (r = -0.64, P
      < 0.003, n = 20). Surprisingly, we observed no change in LS expression on
      neutrophils from SLE patients compared to controls (143 +/- 14 vs 141 +/- 16 RFU,
      respectively) even in patients with the highest activity indices (154 +/- 21
      RFU). In contrast to CD11b/CD18, there was no correlation between LS expression
      and disease activity (r = 0.12, P = NS). Stimulation of neutrophils reduced the
      expression of LS similarly in both controls and SLE patients (67 +/- 3% vs 58 +/-
      4% reduction, respectively) and did not correlate with disease activity (r =
      0.07, P = NS, n = 20). These results show, for the first time, that changes in
      CD11b/CD18 expression do not correlate with LS expression on neutrophils from
      patients with active SLE.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7515336
TI  - The presence of peptidoglycan-polysaccharide complexes in the bowel wall and the
      cellular responses to these complexes in Crohn's disease.
AB  - Interestingly, using a monoclonal antibody, peptidoglycan-polysaccharide
      complexes (PPC) were detected intracellularly in the mucosa and submucosa of the
      bowel wall of Crohn's disease (CD) patients. PPC are the main constituents of the
      gram-positive bacterial cell wall. These PPC were however detected in the normal
      bowel wall also. Therefore, in this study the hypothesis that an enhanced immune
      responsiveness to bacterial antigens plays a pivotal role in the induction or the
      chronicity of CD was tested. As antigens, the peptidoglycan structures of
      intestinal bacteria (Eubacterium aerofaciens or fecal PPC) or of Streptococcus
      pyogenes, the 65-kDa heat shock protein and muramyl dipeptide (MDP), the smallest
      bioactive subunit of peptidoglycan, were used. The proliferative responses of
      peripheral blood (PB) mononuclear cells (MNC) of healthy subjects and patients in
      a remissive stage of CD or an active CD stage were examined. Of this last patient
      group the MNC responses of the mesenterial lymph nodes that drain the inflamed
      gut area were measured also. The responses of PB-MNC of the healthy subjects and
      the patients in a remissive CD stage were not different. Compared to the
      responses in remissive CD, the PB-MNC responses in active CD to the eubacterial
      cell wall and streptococcal cell wall antigen were significantly higher. At the
      inflammation site in active CD, the lymph nodes, the responses to most of the
      bacterial antigens were significantly higher than in the PB. In summary, the
      results show the presence of bacterial peptidoglycan in the bowel wall and the
      immune responsiveness, especially at the inflammation site, to these antigens in
      active CD and therefore present suggestive evidence for the role of peptidoglycan
      in the etiology and/or pathogenesis of CD.

PMID- 7515337
TI  - Effects of intravenous immunoglobulins (IVIG) on peripheral blood B, NK, and T
      cell subpopulations in women with recurrent spontaneous abortions: specific
      effects on LFA-1 and CD56 molecules.
AB  - Polyspecific IgG given intravenously at high dose (IVIG) are increasingly used as
      an immunomodulating therapy in autoimmune diseases. However, very few studies
      have dealt with the action of IVIG on the expression of the leukocyte markers.
      During a clinical trial in which 13 young and healthy women received IVIG to
      prevent unexplained recurrent abortions we have evaluated by flow cytometry the
      action of IVIG on 17 clusters of leukocyte differentiation (CD). We found that
      the IVIG perfusions (0.5 g/kg) induced an increase in the number of
      polymorphonuclear and monocyte cells in the peripheral blood. This effect lasted
      8 days. The IVIG treatment had no effect upon T cell populations stained with
      antibodies specific for CD2, CD3, CD4, CD8 and on CD4+CD45RA+, CD4+CD29+,
      CD8+CD28+, CD8+CD28- subpopulations. A weak decrease in the B cell number was
      observed. The most striking phenomenon was the decrease in the number of CD56+
      cells, whereas CD16+ and CD57+ cells were unaltered. By the double-staining
      technique we showed that CD56+CD16+ cells became CD56-CD16+ cells. Moreover, IVIG
      decrease the expression level of the LFA-1 molecule on monocytes and lymphocytes.
      The other adhesion molecules studied remained steady (CD11b, CD49d, CD49e, CD29,
      CD28, and CD62L). This study has shown that IVIG have no effect on 15 of 17 CD
      used but downmodulate two adhesion molecules playing a key role in the immune
      system.

PMID- 7515338
TI  - Soluble intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte
      adhesion molecule-1 (ELAM-1), and tumor necrosis factor receptor (55 kDa TNF-R)
      in patients with acute Plasmodium falciparum malaria.
AB  - Adhesion of Plasmodium falciparum-infected erythrocytes to vascular endothelium
      is in part mediated by ICAM-1 and ELAM-1 (E-selectin), which can be induced via
      the 55-kDa TNF-receptor (TNF-R55kDa). We have studied serum levels of soluble
      ICAM-1 (sICAM-1), ELAM-1 (sELAM-1), and soluble TNF-R55kDa (sTNF-R55kDa) in 37
      patients with uncomplicated P. falciparum infection and in 17 control subjects in
      Bangkok, Thailand. The serum levels of sICAM-1 were markedly elevated in patients
      prior to treatment (601 +/- 239 ng/ml versus 160 +/- 47 ng/ml in healthy
      controls). In addition, elevated levels of sELAM-1 (53.6 +/- 23.1 ng/ml versus
      21.5 +/- 10.1 ng/ml) and sTNF-R55kDa (4.7 +/- 3.2 ng/ml versus 1.0 +/- 0.4 ng/ml)
      were observed (P < 0.05 for all). Soluble ELAM-1 reached normal levels on Day 3,
      and sTNF-R55kDa on Day 14, while sICAM-1 was still significantly elevated 28 days
      after treatment was started (P < 0.05 for all). A correlation between sTNF-R55kDa
      (P < 0.05) and sELAM-1 (P < 0.05), respectively, with parasitemia prior to
      antimalarial treatment was found. These results suggest that a TNF-mediated
      expression of adhesion molecules induced by the asexual stage of malaria
      parasites serves as an immune-evasion mechanism.

PMID- 7515340
TI  - Chronic pancreatitis in late childhood and adolescence.
AB  - Acute pancreatitis is unusual in pediatric patients, and chronic pancreatitis is
      even less common. Between 1983 and 1988, we diagnosed 24 patients in late
      childhood and adolescence with chronic pancreatitis. Our review revealed that
      chronic pancreatitis presents as recurrent abdominal pain in late childhood and
      adolescence. Individual laboratory and radiological investigations may be normal
      during acute exacerbations of pain, but the determination of serum amylase and
      lipase concentrations--combined with ultrasonography--will accurately identify
      most patients. We found that endoscopic retrograde cholangiopancreatography is a
      valuable tool in the diagnosis of structural abnormalities. Surgical intervention
      may reduce symptoms in patients with structural abnormalities. There is a
      tendency toward decreased frequency and severity of pain as the patients increase
      in age.

PMID- 7515339
TI  - Use of gamma globulin and erythropoietin in a sickle cell aplastic crisis.

PMID- 7515342
TI  - Inhibition of calcium-dependent nitric oxide synthase causes ileitis and
      leukocytosis in guinea pigs.
AB  - As nitric oxide reduces gut epithelial permeability, we designed a study to
      determine if chronic nitric oxide synthase inhibition predisposes the gut to
      inflammation. Nitric oxide synthase (NOS) inhibitors were administered in the
      drinking water ad libitum, for seven days: aminoguanidine (10 micrograms/ml), a
      selective inhibitor of the inducible form of nitric oxide synthase; and NG-nitro
      L-arginine methyl ester (L-NAME, 1, 10, and 100 micrograms/ml), which inhibits
      both the constitutive and inducible forms. Control animals drank tap water only
      or water with D-NAME, the inactive enantiomer. After one week, circulating
      leukocyte count and tissue myeloperoxidase activity were measured. L-NAME (100
      micrograms/ml), but not D-NAME or aminoguanidine, caused a twofold increase in a
      circulating leukocyte numbers. This increase in leukocyte numbers was time- and
      dose-dependent, but the differential count was unaltered. Tissue myeloperoxidase
      (MPO) activity as an index of granulocyte infiltration was comparable in all
      groups in the stomach, jejunum, colon, liver, lung, kidney, heart, and skeletal
      muscle. However, ileal MPO activity was elevated threefold in the L-NAME-(100
      micrograms/ml) treated group (P < 0.05). Results in the D-NAME and aminoguanidine
      groups were similar to controls. L-NAME administration resulted in a reduction in
      NOS activity ([14C]citrulline formation) in the ileum but not jejunum, whereas
      cGMP levels were elevated in both ileum and jejunum. We conclude that chronic
      inhibition of the constitutive form of nitric oxide synthase predisposes the
      ileum to inflammation and leads to a progressive leukocytosis.

PMID- 7515341
TI  - Gastrointestinal peptide hormones during postoperative ileus. Effect of
      octreotide.
AB  - The hypothesis was that postoperative ileus might be caused by a disturbed
      balance between the motor-stimulating hormones, motilin and substance P, and the
      motor-inhibitory hormone, vasoactive intestinal polypeptide, and that octreotide
      might prevent this disturbance and so ameliorate the ileus. In 15 conscious dogs
      with chronic gastrointestinal electrodes, electrical activity was recorded and
      blood was drawn for radioimmunoassay of motilin, substance P, and vasoactive
      intestinal peptide (VIP) during fasting and after a liquid meal. Ileus was then
      induced by celiotomy and intestinal abrasion. During and after operation, five
      dogs received 154 mM NaCl only, five dogs octreotide, 0.19 micrograms/kg/hr, and
      five octreotide, 0.83 micrograms/kg/hr. Plasma levels of motilin, substance P,
      and VIP were changed little by operation, but cyclical increases in plasma
      motilin, which occurred preoperatively during phase III of the interdigestive
      myoelectric complex, were completely abolished postoperatively during ileus, as
      was the complex itself. Octreotide ameliorated the ileus and restored the cyclic
      increases in motilin found in health, nor did it alter plasma substance P and
      VIP. In conclusion, octreotide ameliorates postoperative ileus, but it does not
      do so by increasing plasma motilin or substance P or decreasing plasma VIP.

PMID- 7515344
TI  - [Preparation and identification of monoclonal antibodies against different
      epitopes on TAG-72 antigen].
AB  - The antigen reacted with mAb B72.3 is tumor associated glycoprotein 72 (TAG-72).
      It has been shown that TAG-72 has good specificity, and it can bind to TAG-72
      expressed in great majority of tumors. We have prepared 2 monoclonal antibodies,
      named 72-45 and 72-142, against epitopes on TAG-72 antigen different from those
      reacted with B72.3. The results shown that both antibodies did not react with
      normal adult and fetus tissues but sweat and sebaceous gland and epithelial cells
      of small intestine. The mAb 72-45 gave a 100% (20/20) positive reaction in colon
      cancer and 80% (24/30) positive in lung adenocarcinoma. The mAb 72-142 showed a
      40.5% (9/20) positive reaction in colon cancer and 79.5% (27/34) positive in lung
      adenocarcinoma. The antigenic epitopes to which mAb 72-45 directs is carbohydrate
      and those to mAb 72-142 is also carbohydrate, but also related to sialo-acid
      mucin in molecular structure.

PMID- 7515345
TI  - Intake from an energy-dense porridge liquefied by amylase of germinated wheat: a
      controlled trial in severely malnourished children during convalescence from
      diarrhoea.
AB  - OBJECTIVE: To evaluate the role of an energy-dense diet liquefied with amylase
      rich flour from germinated wheat (ARF) in increasing the energy intake in
      severely malnourished infants and young children and its acceptability to
      mothers. DESIGN: A randomized controlled clinical trial with two sets of
      controls. SETTING: Nutrition rehabilitation unit of a large diarrhoea treatment
      centre where mothers stay with their very severely malnourished children.
      SUBJECTS: 78 severely malnourished children aged 5-18 months just recovered from
      diarrhoea. INTERVENTION: Children were randomly assigned to receive either an
      energy-dense porridge made liquid by adding ARF (test diet) or an unaltered thick
      porridge of similar energy density (control 1 diet), or the porridge made liquid
      with addition of water to have the same viscosity as the test diet but of lower
      energy (control 2 diet), in four major meals a day for 5 days and intake was
      measured; breast-milk was measured by test weighing. Children also received an
      additional three milk-cereal meals a day. RESULTS: The mean energy intake (95%
      CI, P value for difference between test and control) was 385 (339-431), 289 (251
      327, P < 0.005), and 255 (222-289, P < 0.001) kJ/kg.d respectively. Feeding test
      diet was not associated with significant adverse effects e.g. on diarrhoea,
      vomiting, breast-milk intake, and was well accepted by mothers. CONCLUSION: The
      results suggest that use of an energy-dense ARF-treated liquefied porridge
      increases calorie intake by very severely malnourished children during
      convalescence from diarrhoea, and that it does not produce any adverse effect.

PMID- 7515346
TI  - Preparation and structural analysis of oligosaccharide monophosphates obtained
      from the lipopolysaccharide of recombinant strains of Salmonella minnesota and
      Escherichia coli expressing the genus-specific epitope of Chlamydia
      lipopolysaccharide.
AB  - The lipopolysaccharide of the recombinant strain Salmonella minnesota r595-207
      expressing the genus-specific epitope of Chlamydia lipopolysaccharide [Holst, O.,
      Brade, L., Kosma, P. and Brade, H. (1991) J. Bacteriol, 173, 1862-1866] was
      sequentially de-O- and de-N-acylated by mild hydrazinolysis and treatment with 4
      M KOH, respectively. The resulting mixture of compounds was separated by high
      performance anion-exchange chromatography and gel-permeation chromatography,
      yielding four oligosaccharide phosphates two of which were readily identified by
      their 1H-NMR- and 13C-NMR spectra as alpha-Kdo-(2-4)-alpha-Kdo-(2-6)-beta-D-GlcpN
      (1-6)-alpha-D-Glcp N 1,4'-bisphosphate (tetrasaccharide bisphosphate; Kdo = 3
      deoxy-D-manno-octulopyranosonic acid) and alpha-Kdo-(2-8)-alpha-Kdo-(2-4)-alpha
      Kdo-(2-6)-beta-D-GlcpN-(1-6) -alpha-D- GlcpN 1,4'-bisphosphate (pentasaccharide
      bisphosphate) [Holst, O., Broer, W., Thomas-Oates, J.E., Mamat, U. and Brade, H.
      (1993) Eur. J. Biochem. 214, 703-710]. The structures of the other two compounds
      were established by chemical analysis, NMR spectroscopy, and fast-atom
      bombardment mass spectrometry as alpha-Kdo- (2-4)-alpha-Kdo-(2-6)-beta-D-GlcpN-(1
      6)-alpha-D-GlcpN 1-phosphate (tetrasaccharide 1-phosphate) and alpha-Kdo-(2-8)
      alpha-Kdo-(2-4)-alpha-Kdo-(2-6)-beta-D-GlcpN-(1-6) -alpha-D- GlcpN 1-phosphate
      (pentasaccharide 1-phosphate). alpha-Kdo-(2-4)-alpha-Kdo-(2-6)-beta-D-GlcpN-(1-6)
      alpha/beta- D-GlcpN 4'-phosphate (tetrasaccharide 4'-phosphate) and alpha-Kdo-(2
      8)-alpha-Kdo-(2-4)-alpha-Kdo-(2-6)-beta-D-GlcpN-(1-6) -alpha/beta-D-GlcpN 4'
      phosphate (pentasaccharide 4'-phosphate) were prepared from the 1,4'
      bisphosphates isolated from the recombinant strain Escherichia coli F515-207 by
      treatment with alkaline phosphatase and purification by high-performance anion
      exchange chromatography and gel-permeation chromatography. Their structures were
      characterised by chemical analysis, NMR spectroscopy, and fast-bombardment mass
      spectrometry.

PMID- 7515343
TI  - Defective proliferation and regulatory function of CD4+ T cells bearing Leu-8
      homing receptor in primary biliary cirrhosis. Phorbol myristate acetate enhances
      T-cell function.
AB  - The majority of circulating CD4+ T cells express the Leu-8 peripheral lymph node
      homing receptor, and these cells have previously been shown to have suppressor
      inducer and suppressor function. In the present study, it was found that CD4+,
      Leu-8+ T cells from patients with primary biliary cirrhosis (PBC) have a
      significantly (P < 0.01) lower proliferative response when stimulated with
      phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM)
      compared to normal controls. The proliferative response of CD4+, Leu-8- T cells
      was similar in patients and controls. However, the proliferative responses of
      CD4+, Leu-8+ from patients with PBC was normal when cells were stimulated with
      PHA, Con A, anti-CD3 monoclonal antibody, or ionomycin in combination with
      phorbol myristate acetate (PMA). CD4+ T cells from patients with PBC mediated
      normal helper function for PWM-stimulated immunoglobulin synthesis at high T/B
      ratios and their regulatory function was similar to that of normal CD4+ T cells
      that had been irradiated to inactivate their suppressor activity. When CD4+ T
      cells from patients with PBC were precultured with the combination of Con A and
      PMA, they mediated potent inhibitory activity similar to that of normal CD4+ T
      cells. Thus, CD4+, Leu-8+ T cells from patients with PBC have a defect of
      proliferation and suppressor function that is reversed by coculture with PMA.
      This finding suggests that impairment of a PMA-inducible lymphocyte activation
      pathway contributes to abnormal lymphocyte function in PBC.

PMID- 7515347
TI  - Clinical analysis and evaluation of the results of adjuvant treatment
      (radiotherapy and chemotherapy) in ovarian carcinoma.
AB  - The present study was carried out on the material of 486 ovarian cancer patients
      who received radiotherapy and chemotherapy as adjuvant treatment at the
      Oncological Gynaecology Clinic at the Maria Sklodowska-Curie Cancer Center
      Institute of Oncology in Warsaw in the period 1979-1985, following primary
      surgery. The clinical stage of disease advancement was determined on the basis of
      surgery protocols and histological examinations. Radiotherapy was the treatment
      of choice in patients in stages I and II. Irradiation was applied to the pelvis
      minor and para aortal nodes (in patients at stage Ia) or to fields covering the
      entire abdominal cavity (other patients at stage I and II). Chemotherapy was
      given to stage III and IV patients multi-drug therapy, usually including
      Cisplatin, Adriamycin, and Cyclophosphamide, or with one drug (monochemotherapy)
      with the alhylating agents. The largest group of patients under study were women
      with ovarian cancer in stage I (38.8%), the smallest group consisted of patients
      in stage IV (8.5%). Patients in stage III represented 37.5% of all the material.
      Patients aged 50-64 years were most frequently treated (47.3%), the least
      frequent group were the patients aged over 65 (13.2%). The predominating
      histological diagnosis was serous cancer type (48.7%), clear-cell cancer was
      detected least frequently (13.2%). Among all the patients treated 35.4% survived
      5 years after treatment, 69% in stage I, 43.8% in stage II, 8.8% in stage III,
      and 2.5% in stage IV.

PMID- 7515348
TI  - Prostate-specific antigen levels after radical prostatectomy and immediate
      adjuvant hormonal treatment for stage D1 prostate cancer are predictive of early
      disease outcome.
AB  - Detectable prostate-specific antigen (PSA) levels (> or = 0.1 ng/ml) after
      radical prostatectomy (RPx) for prostate cancer are consistent with residual
      disease. Conversely, androgen deprivation therapy that produces 'negative' PSA
      values may not reflect actual disease status. One hundred forty-four patients
      with stage D1 prostate cancer treated with RPx and immediate adjuvant hormonal
      therapy (IAHT) had preoperative PSA tests and serial PSA evaluation up to 5.5
      years postoperatively. Initial postoperative PSA levels (Hybritech method),
      performed a median of 3.7 months postoperatively, were undetectable (< 0.1 ng/ml)
      in 72% of patients, 0.1 ng/ml in 10%, 0.2 ng/ml in 8%, and > or = 0.3 ng/ml in
      10%. Among patients whose initial PSA levels were detectable, 84% attained an
      undetectable level at a median time of 14.4 months postoperatively. The 3-year
      clinical progression rate after the initial postoperative (3.7 months) PSA
      determination was higher (20%) for those patients with a detectable PSA level
      compared with those with an undetectable level (7%; p = 0.09). Mean time to last
      PSA determination was 2.6 years (range 0.2-5.2 years). The course of the follow
      up PSA values was classified for 126 patients as (a) negative (all PSA levels
      undetectable or decreasing), (b) solitary spikes (a one-time increase in PSA
      level), (c) positive (two or more increasing PSA levels), or (d) indeterminate.
      For the 74 patients (59%) with a negative course, only 1 progressed clinically.
      Similarly, no clinical progression has been observed in the 21 patients with
      solitary spikes, and only one progression has been noted in the 12 patients with
      an indeterminate course.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515349
TI  - Transurethral ultrasound-guided laser-induced prostatectomy. Objective and
      subjective assessment of its efficacy for treating benign prostatic hyperplasia.
AB  - We describe our experience with transurethral ultrasound-guided laser-induced
      prostatectomy (TULIP), a new procedure to relieve bladder outlet obstruction
      caused by benign prostatic hyperplasia. This device is composed of a real-time
      7.5 MHz ultrasound transducer coupled to a Nd:YAG laser that fires through an
      intraprostatic balloon. To date, we performed 16 TULIP procedures; all patients
      were evaluated from a subjective point of view by a questionnaire based on the
      Boyarsky scale. They all underwent complete urodynamic studies, including
      flowmetry with measurement of the residual volume (by catheter) and pressure/flow
      studies. Preoperative symptom score ranged between 7 and 14 (mean 11.4).
      Preoperative peak flow rates ranged between 0 and 13 ml/s (mean 6.8). Suprapubic
      drainage was kept for a mean of 11.6 days after the procedure (7-20 days).
      Postoperative acute retention was observed in 4 patients (25%) 5-7 days after the
      procedure. In 13 out of 16 patients, urodynamic obstruction was corrected by the
      procedure. Two patients kept a borderline obstruction. In 1 case transurethral
      resection of the prostate (TURP) was performed for persisting obstruction and in
      another case TURP was performed for persisting untreatable irritative symptoms.
      At 3 months after the operation, the Boyarsky symptom score (11 patients) ranged
      between 3 and 12 (mean 7.7) and peak flow rates ranged between 11 and 30 ml/s
      (mean 16.3). One patient is managed with a suprapubic tube. Retrograde
      ejaculation was observed in 2 out of 9 patients (22.2%). With a mean follow-up of
      6.7 months, we did not observe any late complication.

PMID- 7515350
TI  - Chromodacryorrhea and repetitive hind paw tapping: models of peripheral and
      central tachykinin NK1 receptor activation in gerbils.
AB  - The in vivo pharmacological profiles of the selective tachykinin NK1 receptor
      agonists, [Sar9,Met(O2)11]substance P and GR 73632, were examined in gerbils.
      Both agonists induced a pronounced chromodacryorrhea following intravenous
      injection which was stereoselectively antagonised by the tachykinin NK1 receptor
      antagonist, CP-99,994, but not by its inactive enantiomer, CP-100,263, or the rat
      selective tachykinin NK1 receptor antagonist, RP 67,580. In contrast,
      chromodacryorrhea was not observed following intravenous injection of the
      selective tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A-(4-10), or the
      selective tachykinin NK3 receptor agonist, senktide. These results suggest that
      [Sar9,Met(O2)11]substance P-induced chromodacryorrhea results from activation of
      peripheral tachykinin NK1 receptors. Repetitive hind paw tapping was also
      observed in gerbils but only following intracerebroventricular injection of
      [Sar9,Met(O2)11]substance P or GR 73632. Furthermore, GR 73632-induced hind paw
      tapping was significantly attenuated by co-administration of the peptide
      tachykinin NK1 receptor antagonist, GR 82334, or intravenous injection of CP
      99,994. Thus, in contrast to chromodacryorrhea, repetitive hind paw tapping may
      result from activation of central tachykinin NK1 receptors.

PMID- 7515351
TI  - Effect of dexamethasone on A23187-induced airway responses in the guinea pig.
AB  - We examined the effect of dexamethasone on A23187-induced bronchospasm, pulmonary
      inflammation and airway responses to substance P. Guinea pigs, dosed orally once
      a day for 4 days with dexamethasone (3.0, 10.0 or 30.0 mg/kg) or saline, were
      exposed to an aerosol of A23187 for 12 min or until labored breathing began.
      Postmortem pulmonary gas trapping was used as an indicator of in vivo airway
      obstruction and changes in bronchial responses. Dexamethasone did not alter
      airway obstruction or inflammation 1 h after A23187 exposure. However,
      dexamethasone reduced the enhanced airway responses to substance P and
      bronchiolar/peribronchiolar inflammation 24 h post-A23187. It is possible that
      glucocorticosteroid suppression of A23187-induced pulmonary inflammation was
      important in reducing the increased airway responses to substance P.

PMID- 7515352
TI  - Regional and temporal pattern of expression of nerve growth factor and basic
      fibroblast growth factor mRNA in rat brain following electroconvulsive shock.
AB  - We have previously reported that focally evoked limbic motor seizures rapidly
      increase levels of mRNA encoding nerve growth factor (NGF) and basic fibroblast
      growth factor (bFGF) in specific limbic system areas of the adult rat brain. The
      present studies examined the effect of both minimal and maximal electroconvulsive
      shock, applied via corneal electrodes, on NGF and bFGF mRNA levels in several
      limbic (entorhinal cortex, hippocampus, olfactory bulb) and extralimbic (striatum
      and cerebellum) brain regions. By 5 h following limbic motor seizures induced by
      low-intensity (minimal) electroshock (LES) (0.2 s, 50-70 mA; three times over a 1
      h period), bFGF mRNA was significantly increased in entorhinal cortex and
      hippocampus, but not in the other regions examined. In contrast, tonic extensor
      seizures evoked by maximal electroshock (MES) (0.2 s, 150 mA; three times over a
      1-h period) were associated with a significant increase in bFGF mRNA in all
      limbic and extralimbic regions examined. In the same animals, increases in NGF
      mRNA were limited to entorhinal cortex and hippocampus. Adrenal steroids were not
      required for the seizure-induced increase in NGF or bFGF mRNAs, based on the
      finding that adrenalectomized rats exhibited electroshock-induced increases in
      both NGF and bFGF mRNAs equivalent to the increase observed in sham-operated
      rats. It is suggested that the increase in mRNA levels for the neurotrophic
      factors occurs selectively in those regions which are especially activated by the
      specific seizure model, and represents an adaptive response to repeated
      noninjurious neuronal stimulation.

PMID- 7515353
TI  - Selective loss of [3H]kainic acid and [3H]AMPA binding in layer VI of frontal
      cortex in Huntington's disease.
AB  - Excitatory amino acid neurotoxicity has been proposed to cause the neostriatal
      neuronal degeneration of Huntington's disease (HD); N-methyl-D-aspartate (NMDA),
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate
      receptors have been hypothesized to play important roles in this process. We have
      recently reported a loss of neurons in layer VI of the cerebral cortex in HD.
      Using quantitative autoradiographic methods, we have now measured NMDA, AMPA, and
      kainate receptor binding in the frontal cerebral cortex of the brains of controls
      and individuals with HD. We find no change in NMDA receptor binding but a
      selective decrease in kainate and AMPA receptor binding in layer VI. These data
      suggest that cerebral cortical neurons possessing kainate or AMPA receptors may
      be selectively vulnerable in individuals with HD.

PMID- 7515354
TI  - Increased expression of galanin in the rat superior cervical ganglion after pre-
      and postganglionic nerve lesions.
AB  - Using immunohistochemistry the expression of galanin (GAL) and galanin message
      associated peptide (GMAP) in the superior cervical ganglion (SCG) was
      investigated 2, 4, 7, and 14 days after unilateral transection of the cervical
      sympathetic trunk (decentralization) or after cutting the external and internal
      carotid nerves (axotomy), as well as 7 days after removal of parotid gland
      tissue. In control SCGs including the sympathetic trunk and the carotid nerves,
      very few neurons and fibers were GAL/GMAP-positive. Two and 7 days after
      decentralization, about 5% of all counted neuron profiles in the ipsilateral SCG
      were GAL/GMAP immunoreactive. Immunoreactive cell bodies were distributed
      throughout the SCG, with a greater number in the most caudal portion of the
      ganglion. Many GAL/GMAP-positive nerve fibers were observed in the whole SCG,
      with strongly fluorescent bundles of immunoreactive fibers accumulated at the
      caudal end of the SCG. Several GAL/GMAP-immunoreactive nerve fibers were seen
      ipsilaterally in the external carotid nerve, whereas only a few positive fibers
      could be observed in the internal carotid nerve. About 2% of all counted neuron
      profiles in SCGs ipsilateral to decentralization still contained GAL/GMAP
      immunoreactivity 14 days after the operation. The number of GAL/GMAP-positive
      cell bodies was at least doubled in the contralateral SCGs after decentralization
      compared to controls. After axotomy, about 50% of all counted neuron profiles
      were GAL/GMAP-positive in the ipsilateral SCG and distributed throughout the SCG.
      A strong accumulation of immunoreactive nerve fibers was observed in both the
      internal and external carotid nerves. The number of GAL/GMAP-positive cell bodies
      was slightly increased in the contralateral SCGs. After unilateral removal of
      parotid gland tissue, many GAL/GMAP-positive cell bodies and some fibers were
      observed in the caudal half of the ipsilateral SCG. The number of immunoreactive
      nerve fibers was increased also in the external carotid nerve, but not in the
      internal carotid nerve. In situ hybridization revealed prepro GAL mRNA in about
      5% of all SCG neuron profiles in decentralized SCGs, paralleling the increase
      seen in GAL/GMAP peptide content. There was also a small increase in prepro VIP
      mRNA-positive cells in the caudal part of the SCG. The present results indicate
      that both pre- and postganglionic lesions increase the content of GAL/GMAP in the
      SCG, with a much more pronounced increase after transection of the carotid
      nerves.

PMID- 7515355
TI  - Long distance axonal regeneration of identified lamprey reticulospinal neurons.
AB  - Retrograde labeling with horseradish peroxidase was used to examine the time
      course and extent of axonal regeneration of 12 pairs of individually identifiable
      reticulospinal Muller cells and 2 pairs of Mauthner cells in larval lamprey that
      received transections of the rostral spinal cord in the gill region. With
      increasing recovery times (3-32 weeks post-transection) the descending axons of
      many of these neurons regenerated to progressively more caudal levels of the
      spinal cord. These results confirm that some reticulospinal neurons are capable
      of true regeneration. However, the regenerative capacity of these neurons was not
      uniform, even for neurons in the same brain stem nucleus in close proximity. For
      example, at 32 weeks post-transection some identifiable reticulospinal neurons
      could regenerate their axons to 60% body length or as much as 57 mm below the
      transection site. In contrast, previous studies indicated regeneration distances
      of 5-6 mm. Other neurons showed modest axonal regeneration, while one cell type
      showed very limited regeneration. The factors which may be responsible for the
      variable extent of regeneration among these neurons are considered.

PMID- 7515356
TI  - Combination of the electrogenic ionophores, valinomycin and CCCP, can lead to non
      electrogenic K+/H+ exchange on bilayer lipid membranes.
AB  - The method of pH shift measuring by means of a pH microelectrode was applied to
      measure hydrogen ion fluxes across a planar bilayer lipid membrane (BLM) in the
      presence of the potassium ion ionophore, valinomycin, and a protonophore,
      carbonylcyanide m-chlorophenylhydrazone (CCCP), under conditions of the voltage
      clamp. The voltage dependence of the flux was determined to be in the range of +/
      150 mV under the conditions of both symmetrical KCl as well as a KCl gradient
      across the BLM. Surprisingly, at a clamped zero voltage on BLM a significant
      hydrogen ion flux was observed in the presence of a KCL gradient and both
      valinomycin and CCCP. This finding was interpreted as a result of induction of
      non-electrogenic K+/H+ exchange in the presence of valinomycin and CCCP,
      presumably through the formation of electrically neutral complexes of these two
      ionophores and K+ (H+) ions: valinomycin-K(+)-CCCP- and/or possibly valinomycin
      CCCP(-)-H+.

PMID- 7515358
TI  - Synthetic peptides in the determination of hepatitis A virus T-cell epitopes.
AB  - Computer search for probable T-epitopes of hepatitis A virus capsid proteins was
      performed using an integrated set of programs. Eight segments of the VP1, VP2,
      VP3 and VP4 proteins were chosen and synthesised. Five peptides previously
      examined as probable B-epitopes were used as well. All the peptides were tested
      for their ability to stimulate proliferation of lymph node T-cells primed with
      synthetic peptides. Almost all predicted T-epitopes affected the T-cell
      proliferation. None of the peptides had mitogenic activity. We demonstrated that
      regions 17-33 and 276-298 of VP1 are possible immunodominant promiscuous sites
      activating lymphocytes of all mouse haplotypes.

PMID- 7515360
TI  - An N-linked carbohydrate-containing extracellular matrix determinant plays a key
      role in sea urchin gastrulation.
AB  - During the process of gastrulation in the sea urchin embryo, the vegetal plate
      invaginates to form the archenteron, a long narrow tube that extends across the
      blastocoel. Rearrangement of cells within the archenteron is thought to be a key
      component of the process of archenteron elongation. While these cell
      rearrangements have been well described, the mechanism of the rearrangements and
      the coordination of the movements of individual cells that results in the
      elongation of the archenteron are not well understood. We have identified a
      monoclonal antibody, called ECM 1, that recognizes an N-linked carbohydrate
      containing epitope on several high-molecular-weight basal lamina glycoproteins.
      In an attempt to block the function of this determinant in development, the ECM 1
      antibody was injected into the blastocoel of living embryos and the effects on
      morphogenesis were determined. Injection of intact ECM 1 IgG or monovalent Fab
      fragments blocks cell rearrangements during secondary invagination and cell
      movements during segmentation of the gut. Glycopeptides derived from the
      glycoproteins recognized by ECM 1 also inhibit cell rearrangements during
      secondary invagination when injected into the blastocoel. The inhibitory activity
      of these peptides is eliminated by digestion with N-glycosidase F or pronase,
      enzymes that also disrupt the ECM 1 determinant. ECM 1 recognizes a nonuniformly
      distributed determinant in the basal lamina and blastocoel matrix. This
      determinant is stored in cytoplasmic granules in the unfertilized egg and is
      deposited into the basal lamina by the blastula stage. The determinant becomes
      concentrated in the basal lamina in the vegetal region of the embryo early in
      gastrulation. At the prism stage, the determinant accumulates in the basal lamina
      and blastocoel matrix in the ventral region of the embryo. These data indicate
      that the vegetally localized, N-linked carbohydrate-containing determinant
      recognized by ECM 1 plays an important role in cell movements during archenteron
      morphogenesis in the sea urchin embryo.

PMID- 7515357
TI  - Purification and properties of a novel enzyme from Bacillus spp. T-3040, which
      catalyzes the conversion of dextran to cyclic isomaltooligosaccharides.
AB  - A novel enzyme, cycloisomaltooligosaccharide glucanotransferase (CITase),
      catalyzes the conversion of dextran to cyclic isomaltooligosaccharides by
      intramolecular transglucosylation (cyclization reaction). CITase was purified to
      homogeneity from the culture filtrate of Bacillus sp. T-3040 isolated from soil.
      The Mr of the enzyme was estimated to be 98,000 by SDS-PAGE. The enzyme catalyzed
      the cyclization reaction and gave three cyclic isomaltooligosaccharides
      (cycloisomalto-heptaose, -octase, and -nonaose) at a total yield of about 20%.
      Coupling and disproportionation reactions were also observed. These results
      showed that this enzyme is a multi-functional enzyme which catalyzes
      intramolecular and intermolecular transglucosylation.

PMID- 7515359
TI  - Cyclic GMP in the perfused rat heart. Effect of ischaemia, anoxia and nitric
      oxide synthase inhibitor.
AB  - Working rat hearts perfused with 5.5 mM glucose were submitted to a 10-min period
      of no-flow ischaemia or anoxia. Both conditions stimulated glycogenolysis,
      activated phosphorylase and increased cyclic GMP content, although the time
      course of these changes differed in anoxia and ischaemia. Changes in cyclic GMP
      content were not correlated with glycogenolysis or phosphorylase activation.
      Perfusion with 1 microM L-nitroarginine methylester, an inhibitor of nitric oxide
      synthase, decreased cGMP concentration under normoxic conditions and abolished
      the ischaemia-induced increase in cGMP. The inhibitor decreased the coronary flow
      without affecting the overall working performance of the hearts under normoxic
      conditions.

PMID- 7515361
TI  - Neural crest cells prefer the myotome's basal lamina over the sclerotome as a
      substratum.
AB  - Anterior sclerotome is presumed to be the only somitic tissue that guides neural
      crest cells as they migrate ventrally. In contrast, we report here that crest
      cells prefer the myotome's basal lamina over the sclerotome as a substratum. This
      conclusion stems from four observations. First, crest cells migrating between the
      neural tube and somite invade lumbar and thoracic somites only after the myotome
      has formed a basal lamina, as though they use this basal lamina to penetrate the
      somite. Second, crest cells alter their trajectories dramatically when they
      contact this basal lamina. They abruptly turn laterally and align closely with
      the myotome's basal surface. Third, crest cells invade sclerotome only when they
      fail to contact this basal lamina. For instance, the lateral half of each myotome
      is initially devoid of basal lamina. When the first crest cells reach the lateral
      myotome, they depart from the myotome's basal surface and penetrate lateral
      sclerotome. Only later, when a higher population density prevents some cells from
      contacting the basal lamina, do crest cells penetrate medial sclerotome.
      Conversely, crest cells that migrate between somites do not have access to
      myotome and fail to turn laterally. Fourth, when we prevent myotome development
      by surgically removing its precursor (the dermamyotome), crest cells fail to turn
      laterally within the somite. Instead, they move directly ventrally and colonize
      medial sclerotome. The preference for myotomal basal lamina implies that anterior
      sclerotome is a suboptimal environment for neural crest migration. The myotome's
      basal lamina may facilitate rapid migration through the somite before impediments
      to ventral migration develop.

PMID- 7515362
TI  - Disruption of fast axonal transport in vivo leads to alterations in Schwann cell
      gene expression.
AB  - Following nerve injury, Schwann cells distal to the site of injury down-regulate
      genes associated with myelination. We hypothesized that at least some of these
      alterations were due to the loss of ongoing axon:Schwann cell homeostatic
      signals, as opposed to loss of physical contact and/or inflammatory responses. To
      directly test this hypothesis, we perturbed axonal physiology by selectively
      blocking fast axonal transport via locally cooling the sciatic nerve to 5-8
      degrees C (a cold block). Immunostaining with the monoclonal antibody ED1, which
      recognizes mononuclear phagocytic cells, demonstrated that macrophages did not
      invade the cold-blocked nerve, indicating the lack of an inflammatory response.
      Morphological studies demonstrated that the nerve distal to the cold block showed
      no signs of Wallerian degeneration, with maintenance of normal axon and myelin
      profiles, and confirmed the absence of invading macrophages. Thus, any effects of
      a cold-block treatment were not likely due to inflammatory responses or to loss
      of physical contact between axons and Schwann cells. To determine whether this
      treatment affected Schwann cell phenotype, we examined expression of the major
      myelin protein P0, and p75 NGF receptor, both of which are regulated as a
      function of axon:Schwann cell interactions. Levels of p75 NGF receptor mRNA were
      unaffected by the cold block, while p75 NGF receptor protein levels were
      increased in the region of the nerve immediately adjacent to the cold block,
      presumably reflecting protein accumulation as a consequence of the block to fast
      axonal transport. In contrast, levels of P0 mRNA were decreased in the distal
      nerve in a fashion that indicated modulation of Schwann cell phenotype as a
      function of local axonal microenvironment. These data therefore suggest that P0
      and p75 NGF receptor are regulated as a function of two different aspects of
      Schwann cell:axon communication. Furthermore, these data demonstrate that the
      presence of axon:Schwann cell contact alone is insufficient to maintain Po gene
      expression and indicate that at least some myelin-specific Schwann cell responses
      are dependent upon ongoing biochemical signals generated by the axon and
      maintained by fast axonal transport.

PMID- 7515363
TI  - Cek5, a tyrosine kinase of the Eph subclass, is activated during neural retina
      differentiation.
AB  - The expression of Cek5, a receptor-type tyrosine kinase of the Eph subclass, and
      its variant form Cek5+ were examined in the chick neural retina during
      development. Cek5 is present at high levels at all stages of retinal development
      examined, while Cek5+ is most abundant during differentiation. Cek5 mRNA
      expression and immunoreactivity are evenly distributed in the undifferentiated
      retina. With differentiation, Cek5 becomes concentrated in the inner and outer
      plexiform layers. While only moderate changes in Cek5 protein expression are
      observed throughout retinal development, Cek5 phosphorylation on tyrosine in vivo
      is dramatically increased during differentiation. This suggests that the Cek5
      ligand is expressed at high levels and causes Cek5 activation. Thus, Cek5 is
      likely to play an active role in retinal morphogenesis, particularly during the
      establishment of interneuronal contacts.

PMID- 7515364
TI  - Mitochondrially encoded 16S large ribosomal RNA is concentrated in the posterior
      polar plasm of early Drosophila embryos but is not required for pole cell
      formation.
AB  - In a molecular screen for polar-localized RNAs in Drosophila, we identified the
      mitochondrially encoded 16S large ribosomal RNA (16S RNA) as an RNA that is
      highly concentrated at the posterior pole of early embryos. This high posterior
      accumulation decreases sharply during the first hour of embryogenesis and reaches
      the uniform level found throughout the remainder of the embryo by the time pole
      cells form 1.5 hr after fertilization. At the cellular blastoderm stage the 16S
      RNA is uniformly distributed basal to the nuclei of all somatic cells and is
      present only at low levels in the pole cells and in the apical regions of the
      somatic cells. Transcripts produced by the 12S small rRNA gene are also
      concentrated in the posterior polar plasm and exhibit the same dynamic changes in
      distribution as the 16S RNA. In contrast, NADH dehydrogenase subunit 1 RNA, which
      is transcribed from the same strand of the mitochondrial genome just downstream
      of the 12S and 16S genes, does not exhibit a high posterior concentration but is
      uniformly distributed throughout early embryos. Posterior localization of 16S RNA
      is normal in embryos produced by mothers carrying mutations which affect
      posterior patterning without disrupting the polar plasm or polar granule
      integrity. However, posterior localization of 16S RNA is abolished in embryos
      produced by females carrying maternal-effect mutations that disrupt the posterior
      polar plasm and the polar granules. Ectopic localization of the oskar RNA to the
      anterior pole of the oocyte and early embryo results in anterior assembly of
      polar plasm and anterior budding of functional pole cells. We show that 16S and
      12S RNAs are not concentrated at the anterior pole of such embryos. This leads to
      the conclusion that, although the 16S and 12S RNAs are concentrated in the
      posterior polar plasm during normal development, functional pole cells can form
      in the absence of high levels of these RNAs. These data argue against previous
      hypotheses that the 16S RNA serves an obligatory function in pole cell formation.

PMID- 7515366
TI  - Characterization of the 16S-23S rRNA intergenic spacer of Bartonella
      bacilliformis.
AB  - The 16S-23S intergenic spacer region from the ribosomal RNA (rRNA) operon of
      Bartonella bacilliformis was cloned and characterized. The spacer is 906
      nucleotides (nt) in length and contains the genes encoding isoleucine-tRNA
      (tRNA(Ile)) and alanine-tRNA (tRNA(Ala)). The tRNA-encoding genes are separated
      by 122 nt and are centrally located in the 16S-23S spacer region, with approx.
      300 flanking nt. Genes encoding tRNA(Ile) and tRNA(Ala) have 88.3 and 93.4%
      sequence identity, respectively, to the homologous genes of Rhodobacter
      sphaeroides.

PMID- 7515365
TI  - Genetic organization and enzymatic activity of a superoxide dismutase from the
      microaerophilic human pathogen, Helicobacter pylori.
AB  - Helicobacter pylori (Hp) is a microaerobic human pathogen that has been
      implicated as a factor in the development of chronic type-B gastritis, gastric
      ulcers and gastric carcinoma. The enzyme superoxide dismutase (SOD), a major
      defense mechanism against oxidative damage, catalyzes the breakdown of superoxide
      radicals to hydrogen peroxide and dioxygen. A search for sod genes in Hp,
      employing PCR, revealed that this bacterium contained at least one sod gene. We
      cloned and sequenced a sod from this organism and determined that the deduced
      protein encoded by this gene was most similar to an iron SOD (FeSOD). Northern
      blot and primer extension analysis of Hp RNA showed that the cloned gene is
      monocistronic and is probably transcribed from a sigma 70-like promoter. Assays
      for SOD activities, accompanied by inhibition studies, demonstrated that Hp
      produces an FeSOD. No other SOD activities were seen.

PMID- 7515367
TI  - Fusidic acid-resistant mutants define three regions in elongation factor G of
      Salmonella typhimurium.
AB  - We have sequenced fusA, the gene coding for elongation factor G (EF-G), in 18
      different mutants of Salmonella typhimurium selected as fusidic acid resistant
      (FuR). In addition, we have sequenced two previously described FuR mutants from
      Escherichia coli. In all cases, the resistance is due to a mutation in one of
      three separate regions in fusA. The three clusters of mutant sites superimpose on
      regions that are well conserved, suggesting that they are of a more general
      functional importance. To further classify the mutants, we have measured the
      minimal inhibitory concentration (MIC) for Fu and for two other antibiotics which
      interfere with translocation on the ribosome, kanamycin (Km) and spectinomycin
      (Sp). The levels of resistance to Fu for each of the mutants are significantly
      higher than in the wild type (wt), and vary by about one order of magnitude
      between the highest and the lowest. Most of the mutants are also more resistant
      to Km than the wt, although the level of resistance is low and the variation
      small. In contrast, about half of the mutants are more sensitive to Sp than the
      wt, with only one being more resistant. Only three of the twenty mutants behave
      like the wt with respect to the non-selected phenotypes, KmR and SpR.

PMID- 7515370
TI  - Adipogenic activities in commercial preparations of fetuin.
AB  - Fetuin is frequently in use as a serum substitute especially during the culture
      of differentiating preadipocyte cell lines. We show here, that the commercially
      available crude Pedersen fetuin contains a factor permissive for adipose
      conversion. It can be separated from fetuin by dialysis at acid pH. When 3T3-L1
      cells are cultured in the presence of purified Pedersen fetuin, they fail to
      undergo adipose conversion unless this permissive adipogenic factor is added to
      the culture medium. Insulin-like growth factor I (IGF-I) and growth hormone (GH)
      are not able to replace the factor.

PMID- 7515369
TI  - Characterization of an inhibitor of nitric oxide synthase in human-hand veins.
AB  - The enzyme nitric oxide synthase mediates synthesis of nitric oxide (NO) from 1
      arginine in endothelial cells. NO, also known as endothelium-dependent relaxing
      factor (EDRF), diffuses to smooth muscle cells where it leads to cGMP production
      and dilation. We characterized the potency, efficacy and time course of NG
      monomethyl-l-arginine (l-NMMA) as an inhibitor of bradykinin-mediated,
      endothelium-dependent dilation using the human hand-vein compliance technique. We
      also compared the efficacy of l-NMMA with methylene blue, an inhibitor of
      guanylate cyclase, in blocking bradykinin-mediated vasodilation. l-NMMA potently
      inhibited bradykinin-induced venodilation with a log ED50 of 3.74 +/- 0.52
      (geometric mean of 5.5 micrograms/min). Responses to bradykinin (0.27-555 ng/min)
      were tested in veins pre-constricted with the alpha-adrenergic agonist
      phenylephrine. l-NMMA (25 micrograms/min) decreased bradykinin's maximal
      venodilatory response from 90 +/- 22% to 39 +/- 15% (p < 0.05). Complete recovery
      of bradykinin venodilation was obtained within 155 minutes after stopping l-NMMA
      infusion, indicating that its effects were reversible. In another set of
      experiments we compared the efficacy of methylene blue to l-NMMA; methylene blue
      decreased bradykinin-mediated venodilatory response to 53 +/- 17%; when l-NMMA
      was added, the response was further decreased to 32 +/- 9% (p < 0.002). We
      conclude that l-NMMA is a very efficacious NO synthase inhibitor in human veins
      and it is likely functionally reversible.

PMID- 7515368
TI  - MAG, a novel plasma protein receptor from Streptococcus dysgalactiae.
AB  - The gene encoding a plasma protein receptor from Streptococcus dysgalactiae has
      been cloned and sequenced. The gene product, with a predicted molecular mass of
      approx. 44 kDa, binds alpha 2-macroglobulin (alpha 2 M), serum albumin and
      immunoglobulin G (IgG). By subcloning and expressing various parts of the gene as
      fusion proteins, we found that the three binding activities reside in discrete
      domains of the protein. The single IgG-binding domain, localized in the C
      terminal part of the molecule, shows high homology to streptococcal type-III Fc
      receptors. In the middle of the molecule, there is a stretch of 50 amino acids
      (aa) mediating albumin binding. This region has partial homology with the albumin
      binding domains of streptococcal protein G. The alpha 2 M-binding domain is
      located in the N terminus of the molecule and is composed of a unique aa
      sequence. We call this trifunctional plasma protein receptor, MAG (binds alpha 2
      M, albumin and IgG).

PMID- 7515371
TI  - Immunohistochemical localization of chromogranins A and B and secretogranin II in
      normal, hyperplastic and neoplastic prostate.
AB  - Routinely processed normal, hyperplastic and neoplastic prostatic tissue was
      immunohistochemically investigated with antibodies against chromogranin A and B
      and secretogranin II. In normal and hyperplastic prostates all three peptides
      were immunolocalized in scattered neuroendocrine cells situated within the
      glandular epithelium. In 17 prostatic carcinomas with pronounced neuroendocrine
      differentiation and in a case of prostatic carcinoid, chromogranin B was the
      major component whereas chromogranin A and secretogranin II were virtually absent
      in poorly differentiated (grade III) tumours. Neuroendocrine differentiation in
      prostatic cancer is most likely to be associated with a poor clinical outcome;
      thus, chromogranin B appears to be a useful marker in the histopathological
      diagnosis of these neoplasms.

PMID- 7515373
TI  - Adenomyoepithelioma of the breast with undifferentiated carcinoma component.

PMID- 7515372
TI  - Emergence of alpha 5 beta 1 fibronectin- and alpha v beta 3 vitronectin-receptor
      expression in melanocytic tumour progression.
AB  - Cell adhesion is crucial in the process of tumour progression. As integrins are
      important receptor molecules involved in cell adhesion, we studied the
      distribution of the alpha 1-6, alpha v, alpha IIb, beta 1, beta 3, and beta 4
      integrin subunits in tissue sections of common naevocellular naevi (n = 22),
      dysplastic naevi (16), thin (24) and thick primary cutaneous melanomas (28), and
      melanoma metastases (25). We found correlated expression of alpha 1/alpha 2, of
      alpha 4/alpha 5/beta 3, and of alpha 6/beta 4. Decrease of alpha 6 and beta 4,
      and increase of alpha 4 and alpha v were found to be correlated with melanoma
      progression. Furthermore, expression of alpha 5 and beta 3 was detected only in
      primary melanoma and melanoma metastasis. Our findings indicate that during
      melanoma progression alterations in integrin expression occur, the most striking
      being emergence of alpha 5 beta 1 fibronectin and alpha v beta 3 vitonectin
      receptor.

PMID- 7515374
TI  - Epitope mapping of human ETS1 monoclonal antibody.
AB  - The epitope for E44 monoclonal antibody (mAb) was mapped using mutated ETS1
      proteins lacking different carboxy-terminal regions and by the employment of
      synthetic oligopeptides spanning the epitope region. This epitope lies around
      Arg211 of the human ETS1 protein since substitution of Arg211 by Gln211 in the
      epitope region results in the loss of recognition of the mouse ETS1 protein by
      E44 mAb. Substitution of Leu214 by valine214 in the epitope region (as is found
      in the chicken ETS1 and viral Ets proteins) does not alter the capacity of the
      E44 mAb to recognize this antigen. Taken together, these results suggest that a
      specific ionic interaction is able to play a pivotal role in the recognition of
      the ETS1 protein by the E44 mAb.

PMID- 7515375
TI  - Monoclonal antibodies directed against two different corticotropin-releasing
      factor determinants.
AB  - Two hybridomas secreting monoclonal antibodies (mAbs) against human/rat
      corticotropin-releasing factor (CRF) have been produced by the cell fusion
      technique. Isotyping of the mAbs revealed that both belong to the IgG1 subclass.
      Human serum containing CRF-binding protein inhibits the binding protein inhibits
      the binding of CRF to both mAbs. Modification of lysine residue inhibits binding
      of the mAbs in a different manner. Affinity constants of binding with native and
      histidine-modified antigens have been determined by ELISA. The epitope
      specificity of the mAbs has been examined in competition experiments. No
      competition was detected, suggesting that the mAbs recognize different antigenic
      determinants. Two monoclonal antibodies can be employed in a two-site assay to
      measure CRF.

PMID- 7515376
TI  - Isolation and epitope characterization of human monoclonal antibodies to
      hepatitis C virus core antigen.
AB  - In this study we describe the establishment of two hybridoma cell lines secreting
      human monoclonal antibodies to the 22-kD nucleocapsid protein (core, p22) of the
      hepatitis C virus (HCV). For this purpose we isolated B lymphocytes from an anti
      HCV positive blood donor and infected them with Epstein-Barr (EBV). We obtained
      several lymphoblastoid cell clones secreting antibodies to the recombinant HCV
      core protein. The B-cell cultures were oligoclonally expanded and two of them
      were fused with the (mouse:human) heteromyeloma cell line K6H6/B5. The resulting
      stable hybridomas produce antibodies of the IgG1/kappa (U1/F10) and the IgM/kappa
      (Ul/F11) isotype reacting specifically with the recombinant core protein p22. To
      identify the epitopes recognized by these antibodies we synthesized overlapping
      peptides (13-mer and 6-mer) from the amino terminus of the core amino acid
      sequence. Antibody reactivity to these peptides was analyzed in an immunoblot
      assay. Finally, we were able to define a linear epitope recognized by the Ul/F10
      antibody on the nucleocapsid protein. The antibody shows specificity to the
      sequence N-VYLLPR-C, which corresponds to the amino acids 34-39 of the core
      sequence.

PMID- 7515377
TI  - Heterogeneity of human anti-Golgi auto-antibodies: reactivity with components
      from 35 to 260 kDa.
AB  - The Golgi auto-antigens recognized by five human autoimmune sera were
      characterized with anti-Golgi auto-antibodies. The five sera showed strong anti
      Golgi reactivity, together with weak anti-nuclear reactivity, as assessed by
      indirect immunofluorescence using the human HEp2 epithelial cell line. The Golgi
      auto-antigens recognized by the autoimmune sera were identified by
      immunoprecipitation and immunoblotting of post-nuclear supernatants. These sera
      reacted with at least 14 components of molecular mass (M(r)) 35-260 kDa; three
      components were detected only by immunoprecipitation, six components detected
      only by immunoblotting and five components appear to be detected by both
      techniques. We have previously shown that a patient with Sjogren's syndrome has
      auto-antibodies specific for a 230 kDa Golgi auto-antigens; a bacterial fusion
      protein containing auto-epitope(s) of this Golgi auto-antigen is not recognized
      by the other four autoimmune sera. Taken together, this study shows that the five
      anti-Golgi autoimmune sera recognize distinct sets of auto-antigens which include
      both conformational and/or sequential epitopes.

PMID- 7515379
TI  - Is the unresponsiveness to sumatriptan in cluster headache related to an
      alteration in the 5-HT receptors?
AB  - It is well established that cluster headache shows impaired functions at the
      neuroimmunomodulatory system level. Defects in the expression of receptors for 5
      HT, IL-1 and IL-2 have been found in these patients. Sumatriptan, an agonist
      activity for 5-HT1D receptor, truncates cluster headache attack in 74% of
      patients. Flow cytometric analysis of monocytes expressing 5-HT receptor in
      cluster headache patients showed different trends clearly correlated with the
      clinical response to sumatriptan. Our findings strongly support the concept that
      cluster headache patients which are non-responders to sumatriptan could present a
      block in their 5-HT receptor expression possibly due to specific autoantibodies
      for this receptor site.

PMID- 7515380
TI  - [Therapy of infection-induced multiple organ failure].

PMID- 7515381
TI  - [Hematopoietic growth factors. Current status of therapy].

PMID- 7515378
TI  - Cytomegalovirus infection of vascular endothelial cells alters production of GM
      CSF and G-CSF.
AB  - Infection of human umbilical vein endothelial cells with the clinical isolate of
      human cytomegalovirus (HCMV; at a multiplicity of infection of 2) severely
      suppresses the production of granulocyte-CSF and granulocyte-macrophage-CSF at
      late stages of infection (6 days post infection onwards). The effect was produced
      by actively multiplying virus which indicates that HCMV antigen expression is
      important for this suppression. The suppression in the production of these two
      cytokines was not due to their accumulation inside the cell nor to cell damage or
      lysis after infection.

PMID- 7515383
TI  - "Capsaicin-sensitive" sensory neurons in cluster headache: pathophysiological
      aspects and therapeutic indication.
AB  - Capsaicin, when repeatedly applied to the nasal mucosa of cluster headache
      patients, has been shown to prevent the occurrence of pain attacks. In order to
      investigate the mechanism of the drug's action, we evaluated the effect of
      repeated nasal application of capsaicin on the contents of sensory fibres
      immunoreactive to substance P and CGRP in the rat nasal mucosa. Further,
      considering the possible involvement of the cerebral circulation, we verified the
      effect of a single application of capsaicin on the blood flow velocity of the
      internal carotid and middle cerebral arteries (of both sides) and the basilar
      artery, in a group of healthy humans. The measurements were taken using Doppler
      devices. In order to verify the reproducibility of therapeutic effect of
      capsaicin, we carried out a 2-year follow-up study on patients affected by
      cluster headache (17 by episodic form, 8 by chronic form) who responded
      positively to the first treatment with capsaicin. During this period they were
      treated again with capsaicin in case of re-occurrence of symptoms. Capsaicin
      depletes the fibers immunoreactive to substance P and CGRP in the rat nasal
      mucosa. In the healthy controls, a single application induced vasodilation in the
      internal carotid, whereas middle cerebral arteries and basilar artery were
      narrowed. The results of the follow-up study, demonstrates that in 65% of the
      patients, the beneficial effect of capsaicin was again present when the treatment
      was repeated. In the chronic patients the therapeutic effect was always
      transitory (lasting, at maximum one month).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515382
TI  - Epistaxis and nasotracheal intubation--prevention with vasoconstrictor spray.
AB  - Eighty patients having anaesthesia for oral surgery requiring nasal intubation
      were randomly allocated to be intubated with either a plain Magill red rubber or
      cuffed polyethylene endotracheal tube and in a double blind manner, to receive
      xylometazoline 0.1% vasoconstrictor nasal spray. The extent of any epistaxis
      occurring was assessed by an independent observer. With the Magill tube there was
      bleeding in one out of twenty patients in both the vasoconstrictor group and non
      vasoconstrictor group at intubation and no bleeding in either of the two groups
      at extubation. With the polyethylene tube sixteen out of twenty patients had
      bleeding in the non vasoconstrictor group. This improved to seven out of twenty
      with the administration of vasoconstrictor drops at intubation (chi square 10.2;
      p < 0.01) in the polyethylene tube group. At extubation ten out of twenty
      patients had bleeding in the non vasoconstrictor group improving to two out of
      twenty with the administration of the vasoconstrictor (chi square 9.6; p,0.01).
      The use of the vasoconstrictor xylometazoline helped to reduce epistaxis that
      occurred during nasal intubation and further study into the type of endotracheal
      tube is recommended.

PMID- 7515385
TI  - Expression of sulfated carbohydrate chains detected by monoclonal antibody 91.9H
      in human gastric cancer tissues.
AB  - Expression of sulfated carbohydrate chains in intestinal metaplasia (IM) and
      gastric cancer tissues was immunohistochemically evaluated by using a monoclonal
      antibody (MAb) 91.9H. While normal gastric tissues were negative for MAb 91.9H,
      IM and cancer tissues were positively stained with high frequency. The incidence
      was 67% for IM with chronic gastritis (n = 12), 95% for IM with gastric cancer (n
      = 21), 77% for well and moderately differentiated adenocarcinoma (n = 13), 48%
      for poorly differentiated adenocarcinoma (n = 23), 89% for signet-ring cell
      carcinoma (n = 9) and 100% for mucinous adenocarcinoma (n = 7). When poorly
      differentiated adenocarcinoma cases were divided into two groups, solid (n = 13)
      and non-solid types (n = 10), the incidences were 8% and 100%, respectively.
      These data suggest that MAb 91.9H could be of practical use as a new marker for
      IM and gastric cancer, and may be valuable for subgrouping poorly differentiated
      adenocarcinomas. Analyses of the core proteins for 91.9H epitope were then
      carried out. Comparison of immunostaining of ten poorly differentiated
      adenocarcinoma cases by MAb MUSE11 against MUC1 gene product with that by MAb
      91.9H suggested that 91.9H epitope is not expressed on MUC1. Northern blot
      analysis of 10 pairs of gastric cancer and adjacent normal tissues with a MUC2
      cDNA probe showed that the expression level of MUC2 mRNA was below the limit of
      detection. Thus, 91.9H epitope may be expressed on other proteins than MUC1 or
      MUC2 core proteins in gastric cancer.

PMID- 7515386
TI  - The beta-core fragment of chorionic gonadotropin is not complexed to
      macromolecules in amniotic fluid.
AB  - A prior report claimed that amniotic fluid contains substantial quantities of
      beta-core fragment, a major degradation product of CG metabolism, complexed to
      macromolecules. In an attempt to confirm this finding, we measured beta-core
      fragment concentrations in 36 second- and 22 third-trimester amniotic fluid
      samples in a direct beta-core fragment RIA as well as a total CG RIA and found
      that all of the apparent immunoreactivity could be accounted for by the cross
      reaction of CG and CG beta in the beta-core fragment RIA. Chromatography of
      concentrated pools of amniotic fluid or pregnancy serum failed to reveal a peak
      of CG immunoreactivity in the beta-core fragment elution area. However,
      chromatography after incubation of amniotic fluid or pregnancy serum with 3 mol/L
      ammonium thiocyanate resulted in a peak of apparent CG immunoreactivity in the
      area coinciding with the elution of ammonium thiocyanate and not purified beta
      core fragment. The addition of ammonium thiocyanate to the CG RIA tubes resulted
      in apparent, but spurious, CG immunoreactivity. We conclude that amniotic fluid
      does not contain appreciable amounts of free or complexed beta-core fragment. We
      also were unable to confirm the presence of beta-core fragment complexed to
      macromolecules in pregnancy serum. Our results suggest that the previous studies
      that purported to demonstrate beta-core fragment-macromolecular complexes in
      amniotic fluid and pregnancy serum were reporting artifacts introduced by the
      ammonium thiocyanate used to dissociate beta-core fragment from the putative
      complex or the in vitro generation of beta-core fragment.

PMID- 7515384
TI  - Enhanced vascular permeability in solid tumor is mediated by nitric oxide and
      inhibited by both new nitric oxide scavenger and nitric oxide synthase inhibitor.
AB  - A newly discovered nitric oxide radical scavenger, an imidazolineoxyl N-oxide
      derivative, was used to investigate the role of nitric oxide radical (.NO) in the
      vascular permeability enhancement of solid tumor. Sarcoma-180 solid tumor in ddY
      mice was used for this experiment. Electron spin resonance spectroscopy was used
      to quantitate the reacted and unreacted scavenger. The results showed that
      extensive extravasation, assessed by intravenous injection of Evans blue, could
      be greatly suppressed by both .NO scavenger administered orally and .NO synthase
      inhibitor administrated intraperitoneally. This indicates that .NO is responsible
      for the vascular permeability in solid tumors.

PMID- 7515387
TI  - Effects of replacement dose of dehydroepiandrosterone in men and women of
      advancing age.
AB  - Aging in humans is accompanied by a progressive decline in the secretion of the
      adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS),
      paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although
      the functional relationship of the decline of the GH-IGF-I system and catabolism
      is recognized, the biological role of DHEA in human aging remains undefined. To
      test the hypothesis that the decline in DHEA may contribute to the shift from
      anabolism to catabolism associated with aging, we studied the effect of a
      replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized
      placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg)
      of 6-month duration was conducted. During each treatment period, concentrations
      of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1),
      IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being
      were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h
      sampling at 20-min intervals for GH determinations. DHEA and DS serum levels were
      restored to those found in young adults within 2 weeks of DHEA replacement and
      were sustained throughout the 3 months of the study. A 2-fold increase in serum
      levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was
      observed in women, with only a small rise in androstenedione in men. There was no
      change in circulating levels of sex hormone-binding globulin, estrone, or
      estradiol in either gender. High density lipoprotein levels declined slightly in
      women, with no other lipid changes noted for either gender. Insulin sensitivity
      and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels
      were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased
      significantly for both genders, suggesting an increased bioavailability of IGF-I
      to target tissues. This was associated with a remarkable increase in perceived
      physical and psychological well-being for both men (67%) and women (84%) and no
      change in libido. In conclusion, restoring DHEA and DS to young adult levels in
      men and women of advancing age induced an increase in the bioavailability of IGF
      I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These
      observations together with improvement of physical and psychological well-being
      in both genders and the absence of side-effects constitute the first
      demonstration of novel effects of DHEA replacement in age-advanced men and women.

PMID- 7515388
TI  - A change in the isoforms of human chorionic gonadotropin occurs around the 13th
      week of gestation.
AB  - hCG exhibits a considerable heterogeneity in blood during pregnancy. The overall
      charge of the isoforms of hCG has been shown to be more negative in the early
      than in the latter part of pregnancy. The present study analyzes the change in
      median charge and the charge heterogeneity as pregnancy progresses. The hCG
      activity in sera from 76 women from weeks 6-43 of gestation was measured with a
      noncompetitive time-resolved sandwich fluoroimmunoassay. The median charge and
      degree of charge heterogeneity of the isoforms of hCG in each serum was
      determined by electrophoresis in 0.10% agarose suspension. Median charge was
      expressed as median electrophoretic mobility. Electrophoresis with a high
      resolution revealed that the number of isoforms of hCG in a serum specimen from
      week 36 of gestation was 20-30. A change in median charge was found to occur at a
      limited time period of gestation, around the 13th week. All 16 sera from weeks 6
      10 had isoforms of hCG with a more negative median charge than that of hCG in 21
      sera from weeks 16-43 of gestation. The change in charge was accompanied by an
      increased degree of charge heterogeneity. There was a significant (P < 0.01)
      correlation between median mobility and the concentration of hCG during weeks 11
      15 of gestation, but not before or after this period. There was no relationship
      between the sex of the fetus and the median charge of the isoforms of hCG. The
      data show that a change in the isoforms of hCG, revealed by a change in median
      charge of hCG, occurs at a limited time around the 13th week of gestation. This
      change occurs when the hCG concentration in blood decreases, and the placental
      production of estradiol and progesterone rapidly increases.

PMID- 7515389
TI  - Expression of the genes encoding the insulin-like growth factors (IGF-I and II),
      the IGF and insulin receptors, and IGF-binding proteins-1-6 and the localization
      of their gene products in normal and polycystic ovary syndrome ovaries.
AB  - To discern the potential role of the insulin-like growth factors (IGFs) in
      polycystic ovary syndrome (PCOS), we examined the expression of the genes
      encoding the IGFs, IGF receptors (IGFr), insulin receptor (Ir), and IGF-binding
      proteins (IGFBPs-1-6) as well as the localization of the gene products in
      specific cellular compartments of normal and PCOS human ovaries. Messenger
      ribonucleic acid (mRNA) was localized by in situ hybridization with specific 35S
      labeled human antisense RNA probes, and protein was detected by
      immunohistochemistry using specific antisera. Thecal cells, but not granulosa
      cells (GC), of small antral follicles (3-6 mm) from PCOS ovaries expressed both
      IGF-I and IGF-II transcripts. Abundant IGF-Ir mRNA was found only in GC, IGF-IIr
      mRNA was found in both granulosa and thecal cells, and Ir mRNA was detected in
      all cell types, including granulosa, thecal, and stromal cells. Localization of
      the gene products revealed no IGF-I immunoreactivity; however, immunostaining for
      each of the other gene products was colocalized with its corresponding mRNA. The
      cellular distribution of mRNA and protein in PCOS follicles was indistinguishable
      from that observed in small antral follicles from normal ovaries. In dominant
      follicles, however, IGF-I mRNA was no longer detectable, but abundant IGF-II mRNA
      was expressed exclusively in GC. Although IGF-Ir mRNA was expressed in GC, IGF
      IIr mRNA was found in both granulosa and thecal cells. In follicles taken from
      PCOS ovaries, no IGFBP-1 mRNA was detected, IGFBP-2 mRNA was abundant in both
      granulosa and thecal cells, moderate IGFBP-3 mRNA was found only in thecal cells,
      IGFBP-4 and -5 mRNAs were present in all cellular compartments, and IGFBP-6 mRNA
      was not detected. Localization of the gene products by immunostaining revealed
      that each protein colocalized with its corresponding mRNA. The cellular
      distribution of IGFBP mRNA and protein in PCOS follicles was also
      indistinguishable from that in small antral follicles of normal ovaries, but
      remarkable differences were found in dominant follicles, where abundant IGFBP-1
      mRNA was seen exclusively in GC, IGFBP-2 mRNA in thecal cells, and IGFBP-3 mRNA
      in both granulosa and thecal cells. Moderate expression of the IGFBP-4 and IGFBP
      5 genes was seen in all cell types, including stromal cells, but no IGFBP-6 mRNA
      was detected. Again, each of the gene products colocalized with its corresponding
      mRNA. We conclude the following.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7515390
TI  - Estrogen receptor expression in human pituitary: correlation with
      immunohistochemistry in normal tissue, and immunohistochemistry and morphology in
      macroadenomas.
AB  - Forty-one human pituitary adenoma specimens were examined for the presence of
      estrogen receptor (ER) messenger ribonucleic acid and protein using a combination
      of ribonuclease protection assay, [3H] estradiol ([3H]E2) binding, and ER
      immunohistochemistry. ER messenger ribonucleic acid prevalence was high in PRL
      immunoreactive tumors (2 of 2), moderate in GH/PRL tumors (2 of 5), and low or
      absent (0 of 4) in GH tumors. In the GH/PRL-immunostaining tumors, the presence
      of the ER was uniformly associated with elevated serum PRL levels. Among the
      gonadotropin-immunostaining tumors, 10 of 17 were ER positive; within this group,
      those with gonadotroph adenoma characteristics were ER positive, whereas those
      with null cell/oncocytic characteristics were ER negative. Of the tumors that did
      not immunostain for any known anterior pituitary hormones, 3 of 11 were ER
      positive. ER immunohistochemistry in 14 tumors revealed a 100% correlation with
      ribonuclease protection assay results, whereas [3H]E2 binding, determined in 9
      tumors, showed an 87% correlation. In summary, it appears that PRL and a specific
      class of gonadotropin-immunostaining tumors (identifiable by specific
      characteristics on electron microscope) contain ER, whereas GH-immunostaining
      tumors are ER negative. ER expression in normal pituitary paralleled that in
      macroadenomas (GH, 2.3%; PRL, 50%; FSH, 70%; LH, 83%; TSH, 4%; ACTH, 1%). The ER
      positive tumors represent a subset whose growth and secretory profiles may be
      influenced by the gonadal steroidal milieu or by pharmacological agents that
      affect E2 levels or ER function.

PMID- 7515392
TI  - Glandular kallikreins and prostate-specific antigen are expressed in the human
      endometrium.
AB  - Glandular or tissue kallikrein and prostate-specific antigen (PSA) are members of
      the human kallikrein (KLK) multigene family of enzymes. Various components of the
      glandular kallikrein-kinin system (kallikrein, low molecular weight kininogen,
      bradykinin) have been recently shown to be present or active in the human
      endometrium. We have used the reverse transcriptase-polymerase chain reaction (RT
      PCR) with universal KLK primers to demonstrate kallikrein gene expression in this
      tissue. On Southern blot analysis with gene-specific oligonucleotide probes, we
      have detected expression of the three human KLK genes--KLK1 (kallikrein), KLK2
      (or hGK1) and KLK3 (PSA). The expression of KLK1 and KLK3 was further confirmed
      by sequence analysis of three different endometrial PCR products. These findings
      confirm the presence of a local kallikrein-kinin system in the human endometrium.
      The significance of the novel expression of KLK2 and KLK3 (PSA), previously
      thought to be prostate-specific genes, in the endometrium is unclear. This family
      of enzymes must now be considered potential local regulators of uterine function.

PMID- 7515391
TI  - Phosphorylation of insulin-like growth factor binding protein-1 in patients with
      insulin-dependent diabetes mellitus and severe trauma.
AB  - We have determined the level of phosphorylated insulin-like growth factor binding
      protein-1 (pIGFBP-1) in serum during two catabolic states: diabetes mellitus and
      trauma. Human sera were incubated with [125I]IGF-I for 2 h followed by non
      denaturing PAGE. [125I]IGF-I/IGFBP-1 complexes from serum co-migrated with a pure
      p4IGFBP-1 standard. Complex formation was specifically inhibited by unlabeled IGF
      I. The migration of IGF-I/pIGFBP-1 complexes was retarded by IGFBP-1 antibodies,
      but not by antibodies against IGFBP-2 or IGFBP-3. Sera from three severely
      traumatized patients had up to 12-fold more pIGFBP-1 than sera from age-matched
      controls. The level of pIGFBP-1 was reduced in all three patients upon hospital
      discharge. Sera from three patients with insulin dependent diabetes mellitus
      (IDDM) and severe ketoacidosis (DKA) had more pIGFBP-1 than controls.
      Administration of insulin to DKA patients lowered the level of pIGFBP-1. The
      present study shows that IGFBP-1 exists as a free, high affinity, phosphorylated
      form in vivo during two catabolic states.

PMID- 7515394
TI  - Effects of chronic airway inflammation on the activity and enzymatic inactivation
      of neuropeptides in guinea pig lungs.
AB  - The effects of airway inflammation induced by chronic antigen exposure on
      substance P (SP)-induced increases and vasoactive intestinal peptide (VIP)
      induced decreases in airway opening pressure (Pao), and the recovery of intact
      and hydrolyzed radiopeptide were studied in tracheally perfused guinea pig lungs.
      SP (10(-6) mol/kg) induced a significantly greater increase in Pao in lungs from
      antigen-exposed (30 +/- 5 cm H2O) than saline-exposed animals (15 +/- 1 cm H2O, P
      < 0.05). Significantly more intact 3H-SP and significantly less 3H-SP 1-7, a
      neutral endopeptidase (NEP) hydrolysis product, were recovered from the lung
      effluent of antigen-exposed than saline-exposed animals (P < 0.05). Injection of
      VIP (10(-9) mol/kg) induced significantly more pulmonary relaxation in saline
      exposed compared with antigen-exposed lungs (62 +/- 4%, P < 0.001). In contrast
      to effluent from saline-exposed animals, lung effluent from antigen-exposed lungs
      contained less intact VIP, increased amounts of a tryptic hydrolysis product, and
      no products consistent with the degradation of VIP by NEP. These data indicate
      that inflamed lungs are more sensitive to the contractile effects of SP because
      it is less efficiently degraded by NEP and are less sensitive to the relaxant
      effects of VIP because it is more efficiently degraded by a tryptic enzyme.
      Changes in airway protease activity occur with allergic inflammation and may
      contribute to airway hyperresponsiveness.

PMID- 7515393
TI  - Temporal analysis of the antibody response to HIV envelope protein in HIV
      infected laboratory workers.
AB  - Three laboratory workers have been infected with the IIIB strain of HIV; their
      antibody response to HIV has been studied in serial serum specimens. Because the
      infecting virus is known, the fine specificity of the antibody response was
      studied on the homologous strain of HIV. Anti-p17, anti-p24, anti-gp160,
      CD4/gp120 blocking and neutralizing antibodies developed in parallel. Epitope
      mapping of the anti-gp160 response indicated several regions that consistently
      induced an antibody response. Serum contained antibody which reacted with V3
      specific peptides corresponding to the very tip of the loop and crossreactivity
      was seen with V3 loop peptides from other sequence divergent strains of HIV.
      Antibody to the V1 loop was produced at levels comparable with that seen for the
      V3-loop. Anti-V1 neutralized HIV with a titration curve equivalent to an anti-V3
      monoclonal antibody. Because the infecting virus is known and serial reisolates
      have been obtained, we explored the relationship between production of antibody
      to a given epitope and mutation in the virus. The data suggest that an
      association exists, but do not clearly indicate that antibody drives the
      selection for mutant viruses. The findings presented here provide a fine
      specificity analysis of the evolution of the antibody response to HIV in greater
      detail than has previously been performed.

PMID- 7515395
TI  - Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates
      experimental autoimmune encephalomyelitis in SJL mice.
AB  - Previous work from our laboratory localized nitric oxide to the affected spinal
      cords of mice with experimental autoimmune encephalomyelitis, a prime model for
      the human disease multiple sclerosis. The present study shows that activated
      lymphocytes sensitized to the central nervous system encephalitogen, myelin basic
      protein, can induce nitric oxide production by a murine macrophage cell line.
      Induction was inhibited by amino-guanidine, a preferential inhibitor of the
      inducible nitric oxide synthase isoform, and by NG-monomethyl-L-arginine.
      Aminoguanidine, when administered to mice sensitized to develop experimental
      autoimmune encephalomyelitis, inhibited disease expression in a dose-related
      manner. At 400 mg aminoguanidine/kg per day, disease onset was delayed and the
      mean maximum clinical score was 0.9 +/- 1.2 in aminoguanidine versus 3.9 +/- 0.9
      in placebo-treated mice. Histologic scoring of the spinal cords for inflammation,
      demyelination, and axonal necrosis revealed significantly less pathology in the
      aminoguanidine-treated group. The present study implicates excessive nitric oxide
      production in the pathogenesis of murine inflammatory central nervous system
      demyelination, and perhaps in the human disease multiple sclerosis.

PMID- 7515397
TI  - Tenascin in the injured rat optic nerve and in non-neuronal cells in vitro:
      potential role in neural repair.
AB  - The distribution of tenascin was examined in the lesioned adult rat optic nerve
      and central nervous system (CNS) non-neuronal cells in vitro, by means of a
      double immunofluorescence technique. Tenascin-like immunoreactivity is localized
      to the leptomeninges and astrocytes that border the site of optic nerve
      transection. Anti-tenascin labeling was observed as early as 24 hours after
      transection, when it appeared as a fine interface between leptomeninges and
      neural tissue. The anti-tenascin labeling increased in the cells at this border
      zone during the next 2 weeks, and disappeared 18-21 days after transection. In
      vitro studies further confirmed that both astrocytes and leptomeningeal cells
      express tenascin as detected by immunofluorescence labeling with anti-tenascin
      antibodies. However, the pattern of immunolabeling associated with the two cell
      types differed. Astrocytes showed exclusively punctate labeling of the cell
      surface, while leptomeningeal cells showed mainly coarse, fibrillary, matrix-like
      deposits. Astrocytes and leptomeningeal cells remained segregated when
      cocultured. In these cultures, an increased amount of the fibrillary, matrix-like
      deposits of tenascin was also observed in the region of the interface between
      astrocytes and leptomeningeal cells when these two cell types contact each other.
      Given the antiadhesive and antispreading properties of tenascin, these in vivo
      and in vitro results suggest that tenascin might play a role in the initial
      segregation of leptomeningeal cells from neural tissue at the site of CNS trauma
      during the first 2 weeks after injury, i.e., prior to the formation of a fully
      differentiated glia limitans. Therefore, tenascin may influence the early stages
      in the formation of the glia limitans, and thus prevent the indiscriminate
      migration of leptomeningeal cells into CNS tissue after injury.

PMID- 7515396
TI  - Choline acetyltransferase-immunoreactive cochlear efferent neurons in the chick
      auditory brainstem.
AB  - Cholinergic neurons in the chick auditory brainstem were studied with the aid of
      an antiserum to choline acetyltransferase (ChAT), the biosynthetic enzyme for
      acetylcholine. ChAT-immunoreactive (ChAT-I) neurons were found in a ventrolateral
      and a dorsomedial cell group. The ventrolateral group is a rostrocaudally
      directed column of cells that surround the superior olive (SO), are ventromedial
      to the ventral facial nucleus (VIIv), and are lateral to the nucleus pontis
      lateralis (PL) as far rostrally as the nucleus subceruleus ventralis. Cells in
      the dorsomedial group were found in the pontine reticular formation medial to the
      dorsal facial nucleus and lateral to the abducens nerve root. Occasionally, small
      ChAT-I cells were found in the crossed dorsal cochlear tract and in the medial
      vestibular nucleus near the dorsal border of the caudal nucleus magnocellularis
      (NM). No ChAT-I neurons or fibers were observed in NM, nucleus angularis, nucleus
      laminaris, in the nuclei of the lateral lemniscus, or in the nucleus
      mesencephalicus lateralis pars dorsalis. To determine which cholinergic neurons
      project to the cochlea, a double-labeling technique was used combining ChAT-I and
      the retrograde transport of biotinylated dextran amine (BDA) from the inner ear.
      Double-labeled cells were found bilaterally in both the ventrolateral and
      dorsomedial cell groups, with the exception of large ChAT-I cells dorsal to the
      SO, which do not appear to project to the cochlea. Cholinergic cells that project
      to the cochlea were classified into three morphological groups: multipolar,
      elongate, and round-to-oval. Both the ventrolateral and the dorsomedial cell
      groups appear to have a mixture of these different cell types. The average somal
      area of cholinergic cochlear efferents was 246 microns 2. Only about 70% of the
      cochlear efferent neurons, however, are cholinergic.

PMID- 7515399
TI  - Complex expression of keratins in goldfish optic nerve.
AB  - Keratins are the predominant intermediate filament proteins in the nonneuronal
      cells of the goldfish optic nerve. At least three different keratin pairs are
      expressed in this tissue, indicating an unexpected complexity. Expression of the
      type II keratin ON3 in goldfish optic nerve astrocytes predicts the expression of
      a type I keratin partner. Here we report the cDNA sequence and predicted amino
      acid sequence of two type I keratins from the goldfish optic nerve, designated
      GK48 and GK49. The GK48 protein is the goldfish equivalent of mammalian keratin
      18 (K18) and is the most likely type I keratin partner to the ON3 protein. The
      GK49 protein is similar to the GK50 protein, a type I keratin characterized
      previously from the goldfish optic nerve. The GK48 and ON3 mRNAs are expressed in
      a variety of goldfish tissues, whereas the expression of GK49 mRNA has a more
      limited expression. In addition, in situ hybridization experiments show that the
      expression of the GK48 and ON3 mRNAs are evenly distributed throughout the optic
      nerve, while the GK49 mRNA is expressed along longitudinal lines. These results
      show that there is a diversity of keratin expression within different cell types
      in the goldfish optic nerve.

PMID- 7515398
TI  - Distribution of secretoneurin immunoreactivity in the spinal cord and lower
      brainstem in comparison with that of substance P and calcitonin gene-related
      peptide.
AB  - Secretoneurin is a peptide of 33 amino acids generated in brain by proteolytic
      processing of secretogranin II. The distribution of this newly characterized
      peptide was investigated by means of immunocytochemistry and in situ
      hybridization in the spinal cord and lower brainstem of the rat. The staining
      pattern of secretoneurin immunoreactivity (IR) was compared to that of substance
      P (SP) and calcitonin gene-related peptide (CGRP) in adjacent sections. A high
      density of secretoneurin-IR fibers and terminals was found in lamina I and outer
      lamina II of the caudal trigeminal nucleus and of the spinal cord at all levels,
      around the central canal, and in the sympathetic and parasympathetic areas of the
      lateral cell columns. The ventral horn displayed a low to moderate density of
      secretoneurin-IR. The highest number of secretogranin II mRNA-containing cells
      was found in lamina II of the dorsal horn and in neurons of the dorsal root
      ganglia. In the white matter, secretoneurin-IR was most prominent in the
      dorsolateral part of the lateral funiculus and in the tract of Lissauer. The
      distributions of secretoneurin-IR and SP-IR were strikingly similar. CGRP-IR and
      secretoneurin-IR overlapped in the outer laminae of the dorsal horn, in the
      lateral cell column, and probably in some motoneurons. This study establishes
      that, like SP and CGRP, secretoneurin is a peptide highly concentrated in the
      terminal field of primary afferents and in sympathetic and parasympathetic areas.
      Thus secretoneurin might be involved in the modulation of afferent transmission.

PMID- 7515400
TI  - NGF increases neuritic complexity of cholinergic interneurons in organotypic
      cultures of neonatal rat striatum.
AB  - The influence of NGF on cholinergic interneurons in organotypic roller tube
      cultures of 4 day postnatal rat striatum was examined after 13 to 16 days in
      vitro. Cultures were divided into four groups. The medium of the NGF treated
      group was supplemented with 5 ng/ml NGF, whereas control groups were cultured
      either without NGF, by adding 20 ng/ml neutralising anti-NGF antibody, or by
      adding both NGF and anti-NGF antibody to the medium. Two different cell
      populations were identified by an image analysis system which measured
      acetylcholinesterase staining intensity. It was demonstrated that NGF promotes
      survival of the large, intensely stained population. Eighty computer-assisted
      reconstructions of intensely stained cells, 20 for each treatment group, were
      performed in a random order by means of a neuron tracing system. Axons and
      dendrites were analysed separately. NGF enhanced complexity of neuritic,
      predominantly axonal trees by increasing the number of axonal segments by 91% to
      100% (P < 0.01), the number of dendritic segments by 33% to 63% (P = 0.09 to P <
      0.01), maximal axonal branch order by 37% to 50% (P < 0.05), and maximal
      dendritic branch order by 22% to 37% (P < 0.05). Further evidence of more complex
      neuritic trees was given by Sholl concentric sphere analysis. Anti-NGF antibody
      could block all these effects. General rules of branching architecture were not
      affected by NGF treatment as shown by analysing mean segment length in relation
      to the branch order, branch point exit angles, total tortuosity, Rall's ratio,
      and tapering of neuritic trees.

PMID- 7515401
TI  - Immunohistochemical analysis of the relation between 5-hydroxytryptamine- and
      neuropeptide-immunoreactive elements in the spinal cord of an amphibian (Xenopus
      laevis).
AB  - In mammals, a large proportion of the bulbospinal 5-hydroxytryptamine (5-HT)
      neurons also contain neuropeptides, such as substance P (SP) and galanin (GAL).
      To examine whether a similar coexistence occurs in an amphibian, an
      immunofluorescence double-labelling technique was employed on sections of the
      Xenopus laevis spinal cord. Antisera raised against SP, GAL, enkephalin (ENK),
      corticotropin-releasing factor (CRF), calcitonin gene-related peptide (CGRP), and
      cholecystokinin (CCK) produced a labelling of fibers at all rostrocaudal levels
      of the spinal cord, with the highest fiber densities for SP and ENK and
      intermediate densities for GAL, CCK, and CGRP, while CRF-immunoreactive fibers
      were barely detectable in intact animals. 5-HT-immunoreactive fibers were widely
      distributed in the spinal cord, and they often occurred in the vicinity of
      different types of peptide-immunoreactive fibers. However, no coexistence between
      5-HT and the different peptide immunoreactivities could be detected, although SP
      and GAL immunoreactivities were sometimes found to be colocalized in the same
      fiber. Similar negative results were obtained when 5-HT+SP- and 5-HT+GAL-labelled
      sections were examined in single focal planes with a confocal microscope. After a
      spinal transection, (survival period 6 weeks to 4 months), almost all 5-HT
      immunoreactive fibers below the lesion were lost, and a build-up of
      immunoreactive material occurred in fibers just rostral to the cut. In contrast,
      no significant loss of peptide-immunoreactive fibers occurred, although some
      swollen SP-, GAL-, ENK-, CRF-, and CCK-immunoreactive fibers were present rostral
      to the cut. The distribution of swollen peptide-immunoreactive fibers did not
      overlap with that of the swollen 5-HT-immunoreactive fibers. Although negative
      immunohistochemical data must be interpreted with caution, in conjunction with
      previous studies (Brodin et al. [1988] J. Comp. Neurol. 271:1-18; Sakamoto and
      Atsumi [1991] Cell Tissue Res. 264:221-230), the present results indicate that
      bulbospinal 5-HT neurons in nonmammalian vertebrates cocontain neuropeptides to a
      lesser extent than in mammals.

PMID- 7515402
TI  - Organization of cortical afferents to the rostral, limbic sector of the rat
      thalamic reticular nucleus.
AB  - The organization of limbic cortical afferents to the thalamic reticular nucleus
      (TRN) is described. Wheat germ agglutinin conjugated to horseradish peroxidase
      (WGA-HRP), biocytin, neurobiotin, or fluorescent dextrans was delivered into the
      rat cingulate, retrosplenial, and, for comparison, somatosensory cortices. In
      other species a slab-like arrangement of cortical terminals has been described
      for sensory TRN sectors. Here this is seen in the rat somatosensory sector.
      Terminals from limbic cortices did not cluster into slabs but were found to fill
      the entire thickness of distinct rostral TRN regions. The cingulate and
      retrosplenial recipient TRN regions overlap, as do the projections from these
      cortical areas to anterior thalamic nuclei. Retrosplenial fibres contacted the
      dorsal and rostral TRN, which is known to be connected to the retrosplenial
      recipient anteroventral, anterodorsal, and laterodorsal thalamic nuclei.
      Cingulate terminals occupied more ventral regions of the rostral TRN. This area
      is connected to thalamic nuclei also innervated by the cingulate cortex: the
      mediodorsal and anteromedial nuclei. A loose, but clear, topography could be
      defined for the cingulate-reticular pathway: rostrocaudal and mediolateral
      directions in the cortex are represented by ventrodorsal and rostrocaudal
      directions in the TRN, respectively. This organization of limbic corticoreticular
      pathway corresponds to the arrangement of limbic corticothalamic connections. The
      ultrastructure of the limbic cortical axon terminals was similar to that of the
      cortical boutons (D-type) described previously. The labelled terminals formed
      asymmetrical synapses onto dendritic profiles of reticular neurons. These
      findings, together with data in the literature, show significant morphological
      and connectional differences within the TRN that imply functional
      heterogeneities.

PMID- 7515404
TI  - Dorsal nucleus of the lateral lemniscus in the rat: concentric organization and
      tonotopic projection to the inferior colliculus.
AB  - A basic principle of organization in auditory centers is the topographic
      tonotopic order. Whether this applies to the dorsal nucleus of the lateral
      lemniscus (DNLL), however, is still debated. To clarify this problem, we have
      utilized the neuroanatomical tracers horseradish peroxidase (HRP) and
      biotinylated dextran (BD) injected into different regions of the central nucleus
      of the inferior colliculus (CNIC) in the rat. After large injections of HRP that
      included most of the CNIC, retrogradely labelled neurons were found all across
      the ipsi- and contralateral DNLL, showing that all parts of this nucleus
      innervate the CNIC bilaterally. More neurons were seen consistently on the side
      contralateral to the injection site. Labelled fibers, however, were abundant
      ipsilaterally, but scarce in the contralateral DNLL. Single, small injections of
      HRP or BD into the CNIC resulted in labelling in restricted areas of the ipsi-
      and contralateral DNLL. In coronal sections, the neurons and fibers labelled in
      the ipsilateral DNLL formed a well-defined, ring-shaped structure made of
      dendrites and axons oriented parallel to each other, which we termed "annular
      band." The observation of serial sections revealed that the annular band seen in
      any individual section represents a slice through a more or less complete three
      dimensional, hollow, ovoid structure oriented rostrocaudally. The position and
      diameter of the annular band changed as the injection site was shifted along the
      tonotopic axis of the CNIC. Single injections placed in the ventromedial, high
      frequency region of the CNIC produced a large annular band along the periphery of
      the DNLL. After injections placed in progressively more dorsolateral, lower
      frequency regions of the CNIC, the annular band became smaller in diameter and
      occupied a successively more central position in the DNLL. Double injections
      along the tonotopic axis of the CNIC resulted in two roughly concentric annular
      bands. The labelled neurons and fibers in the contralateral DNLL systematically
      occupied a position symmetric to the annular band seen ipsilaterally. These
      findings indicate that the rat DNLL is primarily composed of neurons with
      flattened dendritic arbors and flattened fields of terminal fibers. These two
      elements intermingle, forming concentric layers around the geometric center of
      the nucleus. The axons of neurons within corresponding layers on the two sides
      converge onto the CNIC of both sides in a strict topographic fashion: the
      peripheral layers project to the ventromedial, high-frequency region of the CNIC,
      and the central layers project to the dorsolateral, low-frequency region. These
      results suggest that the concentric arrangement of the DNLL is the substrate of
      its tonotopic organization.

PMID- 7515406
TI  - Nonaggressive management of the illnesses of severely demented patients: an
      ethical justification.

PMID- 7515403
TI  - Biotin staining in the giant fiber systems of the lobster.
AB  - The avidin-biotin-complex method is a popular immunocytochemical technique. This
      method labels consistently a group of neurons in the lobster ventral nerve cord
      in the absence of primary antibodies. The specific staining is due to a
      relatively high level of endogenous biotin (or biocytin) in these neurons. These
      biotin-positive neurons are located in the supraesophageal, thoracic, and
      abdominal ganglia. Intraaxonal injection of Lucifer yellow followed by Texas red
      conjugated streptavidin staining reveals that the neurons are members of the
      medial giant (MG) and lateral giant (LG) systems, which are important in
      mediating rapid tail flipping during escape maneuvers. In neuronal somata,
      staining is restricted to the cytoplasm. Within MG axons, staining appears as
      punctate, subaxolemmal structures. Preincubating nerve cords in biocytin or
      direct intraaxonal injection of biocytin enhances staining of these punctate
      organelles. In LG axons, staining is localized to fragments of braided
      filamentous structures that also appear to be associated with the axolemma.
      Preincubation of ventral nerve cords in various concentrations of biocytin
      results in the appearance of additional groups of stained neurons, suggesting
      that there are subsets of neurons with specific biocytin-uptake or -retention
      mechanisms. In the crayfish, biotin-positive staining is confined to the MG
      neurons; the LG neurons are not stained. In the earthworm, no staining is
      observed in the MG and LG axon escape systems. In the goldfish, no biotin
      staining is seen in the Mauthner neurons and their axons. The significance of
      specific localization of biotin or biocytin to subsets of neurons is unclear. It
      may reflect the presence of high levels of biocytin moieties on biotin-dependent
      enzymes. Biotin is an important cofactor in the catalytic functions of several
      decarboxylases crucial in energy production and lipogenesis. Axons of the giant
      fiber systems in lobsters and crayfish may have high energy and fatty acid
      synthesis requirements. Increased levels of biotin accumulation may also be
      related to other functions of the giant axon systems, such as the formation of
      electrical synapses among themselves and with phasic motoneurons.

PMID- 7515405
TI  - Impact of special care unit for patients with advanced Alzheimer's disease on
      patients' discomfort and costs.
AB  - OBJECTIVE: To compare outcomes in patients with the clinical diagnosis of
      probable dementia of the Alzheimer type (DAT) cared for in a Dementia Special
      Care Unit (DSCU) with those in traditional long-term care (TLTC). DESIGN: Two
      year prospective cohort study. SETTING: Two Veterans Administration Hospitals.
      The DSCU concentrated on assuring patients' comfort instead of promoting maximal
      survival; in some patients this excluded transfer to acute medical settings, the
      use of antibiotics, and tube feeding. MEASUREMENTS: Data were collected regarding
      disease severity, patient discomfort, use of medical resources, and mortality
      rate. RESULTS: Patients at both settings were similar on baseline measures, and
      most were severely demented. The monthly levels of observed discomfort were lower
      in DSCU than in TLTC patients. The costs of medications, radiology, and
      laboratory procedures were lower in DSCU than in TLTC patients. DSCU patients
      were also transferred less frequently to an acute medical setting. The average 3
      month cost for a DSCU patient was $1477 less than the cost of care for a TLTC
      patient. However, DSCU patients with lower severity of DAT had a higher mortality
      rate then TLTC patients. CONCLUSIONS: These results suggest that management of
      patients with advanced DAT on a DSCU using a palliative care philosophy may
      result in less patient discomfort and lower costs than management on a TLTC.

PMID- 7515407
TI  - Optimization for the detection of hepatitis C virus antigens in the liver.
AB  - To optimize the detection of hepatitis C viral antigens in liver tissue, cryostat
      and formalin-fixed, paraffin-embedded liver sections from 21 patients with
      chronic hepatic C viral infection were studied. For cryostat sections, six
      different fixatives were compared. Sixteen primary antibodies were tested: nine
      different mouse monoclonal anti-hepatitis C virus-core antibodies, a human
      monoclonal anti-hepatitis C virus-non-structural 4, and six rabbit polyclonals
      directed against synthetic peptides of the hepatitis C virus core, envelope, and
      non-structural 3, non-structural 4, non-structural 5. Three detection systems, 3-
      and 5-step peroxidase-antiperoxidase and avidin-biotin complex, were examined. In
      cryostat sections, acetone/chloroform formation consistently produced the best
      signal-to-background ratio. Five anti-hepatitis C virus-core monoclonals which
      recognize amino acid sequence 26-45 of the hepatitis C virus-core region
      consistently detected the viral antigen, but not the monoclonals directed against
      39-74 of the hepatitis C virus-core region. The human anti-hepatitis C virus-non
      structural 4, which reacts to amino acid sequence 1700-1705, also regularly
      detected viral antigen. The rabbit polyclonals produced either negative or
      nonspecific staining. The 5-step peroxidase-antiperoxidase provided the strongest
      signal and the avidin-biotin system produced high background consistently.
      Overall, hepatitis C virus core and non-structural 4 antigens were detected in
      71% and 57% of the patients studied. Of the 16 patients seropositive for
      hepatitis C virus RNA, 75% and 69% had detectable hepatitis C virus core and non
      structural 4, in contrast to 60% and 20% of the five hepatitis C virus RNA
      seronegative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515409
TI  - Differentiation between parasystole and extrasystoles. Influence of vagal
      stimulation on parasystolic impulse formation.
AB  - Recently, it has been shown that when a sinus impulse falls late in the
      parasystolic cycle, it usually hastens the next ectopic discharge. Thus, in many
      cases, the classic criteria for the diagnosis of parasystole (ie, varying
      coupling intervals and constant shortest interectopic intervals) cannot be used.
      To differentiate between parasystole and extrasystoles in such cases, the
      influence of vagal stimulation on parasystolic impulse formation was investigated
      in seven cases of "true" parasystole in which one or more "pure" ectopic cycles
      without any intervening nonectopic QRS complexes were found spontaneously. In all
      cases pure ectopic cycles were found during sinus arrest caused by vagal
      stimulation; namely, none of the cases showed extreme prolongation of the
      parasystolic cycle. These results strongly suggest that instead of the classic
      criteria, vagal stimulation causing temporary sinus arrest is the optimal method
      for differentiation between parasystole and extrasystoles in cases without
      spontaneous pure ectopic cycles.

PMID- 7515410
TI  - Pentacyclic triterpenes derived from Maprounea africana are potent inhibitors of
      HIV-1 reverse transcriptase.

PMID- 7515408
TI  - Prospective study of screening for hepatocellular carcinoma in Caucasian patients
      with cirrhosis.
AB  - Screening is widely used to detect early hepatocellular carcinoma in Asian
      patients with cirrhosis. Its effectiveness in Caucasian patients has been
      suggested, but remains to be proven. Therefore we prospectively studied 118
      French patients (68 males, 50 females, age 55 +/- 12) with Child-Pugh A or B
      cirrhosis (alcoholic in 82) and without detectable hepatocellular carcinoma. The
      screening program consisted of ultrasound examination of the liver and
      determination of blood alpha-fetoprotein and des-gamma-carboxyprothrombin levels
      every 6 months. The median follow up was 36 months (range 4-48). Only four
      patients were lost to follow up. Fourteen hepatocellular carcinomas were
      detected, in six cases by ultrasonography alone, in four by alpha-fetoprotein
      alone, in three by ultrasonography and alpha-fetoprotein and in one case by
      ultrasonography and des-gamma-carboxyprothrombin, but never by des-gamma
      carboxyprothrombin alone. The tumor presented as a unique nodule in nine
      patients. The tumor was less than 3 cm in diameter without portal thrombosis or
      metastasis in three cases. Surgery was performed in only one case. In this study,
      the annual incidence of hepatocellular carcinoma was high (5.8%), but the
      screening methods used did not effectively identify potentially resectable tumors
      in Caucasian patients with cirrhosis.

PMID- 7515411
TI  - Autoimmune T cell repertoire in optic neuritis and multiple sclerosis: T cells
      recognising multiple myelin proteins are accumulated in cerebrospinal fluid.
AB  - Monosymptomatic unilateral optic neuritis is a common first manifestation of
      multiple sclerosis. Abnormal T cell responses to myelin components including
      myelin basic protein (MBP), proteolipid protein (PLP), and myelin-associated
      glycoprotein (MAG) have been implicated in the pathogenesis of multiple
      sclerosis. Antigen-reactive T helper type 1 (Th1)-like cells that responded by
      interferon gamma (IFN-gamma) secretion on antigen stimulation in vitro were
      counted. Untreated patients with optic neuritis and multiple sclerosis had
      similarly raised levels of T cells recognising MBP, PLP, and MAG in peripheral
      blood. Such T cells were strongly enriched in CSF. None of these myelin antigens
      functioned as immunodominant T cell antigen characteristic for optic neuritis or
      multiple sclerosis. The autoimmune T cell repertoire was not more restricted in
      optic neuritis (as an example of early multiple sclerosis). The autoreactive T
      cell repertoires differed in blood compared with CSF in individual patients with
      optic neuritis and multiple sclerosis. No relations were found between
      specificity or quantity of autoreactive T cells in blood or CSF, and clinical
      variables of optic neuritis or multiple sclerosis, or occurrence of oligoclonal
      IgG bands in CSF. The role of raised MBP, PLP, and MAG reactive Th1-like cells
      found in optic neuritis and multiple sclerosis remains unexplained.

PMID- 7515412
TI  - Continuous infusion bleomycin in AIDS-related Kaposi's sarcoma.
AB  - PURPOSE: To determine the toxicity, response, and survival rate of 72-hour
      continuous infusion bleomycin administered to patients with AIDS-related Kaposi's
      sarcoma. PATIENTS AND METHODS: Seventeen patients with biopsy-proven and
      measurable-disease AIDS-related Kaposi's sarcoma were treated with a continuous
      infusion of bleomycin at a dose of 20 mg/m2/d for 3 days every 3 weeks. All
      patients were evaluated for toxicity, response, and survival using the National
      Cancer Institute common toxicity criteria, and both the Eastern Cooperative
      Oncology Group (ECOG) and AIDS Clinical Trials Group (ACTG) response criteria.
      Fourteen of 17 patients (82%) enrolled had at least two on-study poor-risk
      factors by ACTG staging criteria. RESULTS: A total of 59 cycles of therapy were
      administered. Only one cycle (2%) was complicated by an absolute neutrophil count
      less than 500, and there were no episodes of febrile neutropenia. Fifty-four
      percent of cycles were associated with fever during the infusion, and five cycles
      (8%) were complicated by grade 3 rash. There were no other clinically significant
      (> or = grade 3) toxicities. There were seven partial remissions (41%) by ECOG
      criteria (95% confidence interval, 18% to 64%) and 11 partial remissions (65%) by
      ACTG criteria (95% confidence interval, 42% to 88%). Three of five (60%)
      previously treated patients had a partial remission with this schedule of
      bleomycin. The median survival duration was 7 months, with a range of 2.5 to 25
      months. CONCLUSION: This continuous infusion schedule of bleomycin is active in
      patients with advanced-stage AIDS-related Kaposi's sarcoma and has acceptable
      toxicity. This regimen should be further evaluated in patients with earlier stage
      Kaposi's sarcoma and as salvage therapy.

PMID- 7515413
TI  - Incidence of neutropenic fever in patients treated with standard-dose combination
      chemotherapy for small-cell lung cancer and the cost impact of treatment with
      granulocyte colony-stimulating factor.
AB  - PURPOSE: We sought to determine the incidence of neutropenic fever associated
      with the use of standard-dose combination chemotherapy for small-cell lung cancer
      (SCLC) and to use these data as a template to analyze the costs and benefits of
      the routine use of granulocyte colony-stimulating factor (G-CSF). PATIENTS AND
      METHODS: We retrospectively reviewed records of 137 consecutive, unselected
      patients with SCLC treated with combination chemotherapy from January 1987 to
      March 1992. Admission criteria for neutropenic fever were temperature > or = 38.5
      degrees C and an absolute neutrophil count < or = 500/microL. Neutropenic fevers
      were managed with a 25% dose reduction of the myelosuppressive drugs in
      subsequent cycles. Charge estimates for hospitalization ($1,244 per day) and G
      CSF use ($2,027 per course) were estimated by reviewing charges to patients at
      Indiana University hospitalized for neutropenic fever or treated with outpatient
      G-CSF. We imposed assumptions from the Neupogen (filgrastim; Amgen Inc, Thousand
      Oaks, CA) licensing trial regarding the effectiveness of G-CSF and the Indiana
      University charge estimates on three models of G-CSF use: (1) preemptive--with
      all courses of chemotherapy, (2) reactive--with all cycles of chemotherapy
      following a neutropenic fever, and (3) dose reduction only (no G-CSF)--to derive
      charge estimates for G-CSF use. RESULTS: Records of 137 patients with SCLC were
      identified and reviewed. The incidence of neutropenic fever was 12% in the first
      cycle of chemotherapy, and 18% overall, compared with the placebo- and G-CSF
      treated arms of the Neupogen licensing trial, in which the incidence of
      neutropenic fever was 77% and 40%, respectively. Other therapeutic outcomes, such
      as neutropenic septic deaths, response rates, and survival, were comparable. We
      derived the following charge estimates for the three models of G-CSF: (1)
      preemptive--total charges = $1,287,481; (2) reactive--total charges = $276,154;
      and (3) dose reduction only--total charges = $192,820. CONCLUSION: The incidence
      of neutropenic fever with standard-dose chemotherapy for SCLC was 18%. Routine
      use of G-CSF in SCLC patients treated with standard-dose chemotherapy appears to
      be expensive and is not associated with an obvious therapeutic benefit or cost
      savings. We suggest that careful analysis of the incidence of infectious
      complications, rather than granulocyte nadir and duration, be performed, and that
      clinical guidelines for the use of these effective, but expensive, products be
      developed.

PMID- 7515416
TI  - The expression of transforming growth factor type beta in fetal and adult rabbit
      skin wounds.
AB  - Transforming growth factor, subtype beta (TGF-beta) exists in several isoforms
      and is known to have important roles in adult wound healing by promoting collagen
      and extracellular matrix component deposition. It is also believed that TGF-beta
      influences normal developmental processes during embryo-genesis.
      Immunolocalization of two isoforms, TGF-beta 1 and TGF-beta 2, in healing fetal
      and adult rabbit skin wounds shows distinctly different forms of expression of
      these molecules. TGF-beta 1 and TGF-beta 2 are both expressed within the
      developing fetal dermis, but no differential upregulation in the area of the
      healing wound is noted. In contrast, the expression of TGF-beta 1 and TGF-beta 2
      is increased in adult wounds by day 7 after wounding, within macrophages that are
      abundant by this time. High levels of TGF-beta 1 and TGF-beta 2 within adult
      wounds might indicate that the relative paucity and differential distribution of
      these factors in fetal wounds are important in the production of scar in adults
      and the absence of scar in the fetus. Further, these patterns of expression
      suggest fundamental differences between fetal and adult tissues in accomplishing
      wound repair.

PMID- 7515415
TI  - Hypoxemia and increased fetal hemoglobin synthesis.
AB  - Fetal hemoglobin (HbF) synthesis in children with congenital cyanotic heart
      disease was compared that in normal children. Children with hypoxemia had higher
      levels of hemoglobin, total HbF, and HbF synthesis. In these children there was
      also an inverse correlation between HbF synthesis and oxygen content, as well as
      between HbF synthesis and hemoglobin concentration. Thus hypoxemia increases HbF
      synthesis.

PMID- 7515414
TI  - Deoxyribonucleic acid, ribonucleic acid, and protein in the placentas of normal
      and selected complicated pregnancies.
AB  - Placenta from uncomplicated term pregnancies resulting in the birth of male
      infants weighing between 2900 and 3800 grams were analyzed for deoxyribonucleic
      acid (DNA), ribonucleic acid (RNA), and protein content. The mothers of the
      infants all had pre-pregnancy weights within +/- 15 percent expected body weight
      for body frame, according to the Metropolitan Life Tables. There were no
      significant differences, as regards the content of DNA, RNA and protein, between
      the placental cotyledons. Nine placenta from mothers giving birth to growth
      retarded infants were analyzed along with the placenta from six mothers with
      insulin dependent diabetes mellitus. A trend suggesting less DNA in the placenta
      of the severely growth retarded (symmetric) infants when compared with placenta
      from the normal pregnancies was not noted in the less severely growth retarded
      (asymmetric) infants. The placenta from the infants of diabetic pregnancies
      contained DNA and RNA in amounts similar to that found in normal pregnancy
      placenta but the protein content was greater.

PMID- 7515417
TI  - Absorption enhancement of intrapulmonary administered insulin by various
      absorption enhancers and protease inhibitors in rats.
AB  - The effects of absorption enhancers and protease inhibitors on the pulmonary
      absorption of insulin were examined by means of an in-situ pulmonary absorption
      experiment. Absorption enhancers used in this study were sodium glycocholate,
      linoleic acid-surfactant mixed micelles and N-lauryl-beta-D-maltopyranoside
      whereas aprotinin, bacitracin and soybean trypsin inhibitor were used as protease
      inhibitors. The absorption of insulin from the lung was evaluated by its
      hypoglycaemic effect. In the absence of these additives, a slight hypoglycaemic
      effect was obtained following intrapulmonary administration of insulin. However,
      we found significant and continuous hypoglycaemic effects after the insulin
      administration with these additives. N-Lauryl-beta-D-maltopyranoside and
      bacitracin appeared to be more effective for enhancing the pulmonary absorption
      of insulin than the other adjuvants. These findings suggest that the use of these
      two adjuvants would be a useful approach for improving the pulmonary absorption
      of insulin.

PMID- 7515420
TI  - Salmeterol inhibits anaphylactic histamine release from guinea-pig isolated mast
      cells.
AB  - Salmeterol (1 nM-100 microM) showed an inhibitory action on anaphylactic
      histamine release from mast cells, isolated from pleural and peritoneal cavities
      of actively sensitized guinea-pigs and stimulated by incubation with allergen.
      The effect is concentration-dependent and is reduced by the beta-adrenoceptor
      antagonist propranolol (1 microM). This study supports the hypothesis of an anti
      inflammatory property of salmeterol, which concerns cells involved in the early
      phases of asthma.

PMID- 7515418
TI  - Effect of terfenadine on substance P and vasoactive intestinal polypeptide
      concentrations in nasal secretions from patients with nasal allergy.
AB  - Before terfenadine treatment, the mean substance P and vasoactive intestinal
      polypeptide (VIP) concentrations in nasal secretions from nasal allergy patients
      tended to be higher than the values of healthy subjects. During terfenadine
      treatment, the mean substance P concentrations in nasal secretions from patients
      allergic to house dust or pollen were significantly decreased to 62 and 39% of
      the initial values, respectively. The mean VIP concentrations in nasal secretions
      from the house dust allergy patients and the pollen allergy patients were
      significantly decreased to 52 and 18% of the initial values, respectively. Plasma
      substance P and VIP concentrations were not affected by nasal allergic symptom
      and terfenadine treatment.

PMID- 7515419
TI  - Antithyroid action of ketoconazole: in-vitro studies and rat in-vivo studies.
AB  - Inspection of the chemical structure of ketoconazole indicates that it may have
      antithyroid activity. The antithyroid action of this drug was demonstrated in
      vitro and in-vivo. In-vitro, it was found to form a complex with iodine
      (formation constant Kc 141 L mol-1), and to inhibit lactoperoxidase (IC50 2 x 10(
      4) M). Its effects in-vivo in the rat were assessed by assay of circulating
      thyroxine, and from the histological appearance of the thyroid gland. Thyroid
      gland weight was increased in rats treated with ketoconazole.

PMID- 7515421
TI  - Caregivers' expectations of future learning of dependents with a developmental
      disability.
AB  - Attitudes and expectations of caregivers affect the development of children,
      including those with a developmental disability. The purpose of this study was to
      examine caregivers' expectations of their dependent with a developmental
      disability and caregiver attributions in relation to these expectations. Primary
      caregivers (N = 35) were interviewed about their expectations and attributions
      related to the dependents' achievements. Expectations were measured by the
      Predictive Adaptive Ability Questionnaire (PAAQ). Expectations were significantly
      predicted by the degree of developmental delay and number of handicaps.
      Caregivers expected less of dependents who had a lower developmental
      age/chronological age ratio than for dependents whose developmental level more
      closely approximated the chronological age. Results suggest that nurses should
      assess caregivers' expectations for the future development of their dependent
      with a developmental disability and the basis for those expectations.

PMID- 7515422
TI  - Nursing care for children with developmental disabilities in Israel: Part I.

PMID- 7515423
TI  - Prosthetic graft seeding: breathing new life into old grafts.
AB  - A major constraint in vascular surgery is the failure of the currently available
      prosthetic grafts to match the patency of autogenous vein below the inguinal
      ligament. Endothelial seeding aims to produce an endothelial lining which is
      otherwise absent from prosthetics. This could improve patency by preventing
      thrombosis and the release of mitogens by activated platelets implicated in the
      development of neointimal hyperplasia. Experimental evidence supports the
      potential of the technique but clinical trials have been less conclusive. A
      number of problems need to be solved if this application of cell biology is to
      become a part of vascular surgical practice.

PMID- 7515424
TI  - The ileo-anal reservoir: results from an evolving use of stapling devices.
AB  - Thirteen patients had a hand-sewn pouch-anal anastomosis (group A) during
      restorative proctocolectomy for familial adenomatous polyposis. Median length of
      follow-up since ileostomy closure was 41.5 months (range 30-56 months). Median
      stool frequency per 24 h was 4.5 (range 2-5). Six patients were fully continent,
      three were incontinent to flatus and three patients were occasionally incontinent
      to liquid stool. Three patients suffered nocturnal seepage but all patients could
      defer the urge to defaecate by at least 15 min. Fourteen patients (familial
      adenomatous polyposis: seven; ulcerative colitis: six; intractable constipation:
      one), had a totally stapled ileal J pouch and pouch-anal anastomosis (group B).
      Five patients did not have a defunctioning ileostomy while nine patients did.
      Median follow-up after ileostomy closure or one-stage restorative proctocolectomy
      was 17.5 months (range 1-30 months). Median frequency of bowel movement per 24 h
      was 4 (range 2-6). Eleven patients had full continence and three patients suffer
      occasional incontinence to liquid stools. Two patients have nocturnal seepage but
      all can defer the urge to defaecate by more then 15 min. There was no significant
      difference in physiological parameters between the two groups.

PMID- 7515425
TI  - Endoscopic treatment of vesico-ureteric reflux in children by subureteric Teflon
      injection: the Edinburgh experience.
AB  - This is an audit of 50 consecutive children who were treated in Edinburgh with
      subureteric Teflon injection (STING) for vesico-ureteric reflux between May 1988
      and March 1992. There were 68 ureters treated with a total of 89 injections.
      Twenty-nine ureters (42.6%) were cured after a single injection and another 20
      ureters were cured after a second injection (74.2%). These results revealed a
      decreasing failure rate with experience and compared favourably with other
      published works. STING is a well-tolerated, simple, effective alternative to
      medical and surgical treatment for vesico-ureteric reflux in children.

PMID- 7515426
TI  - Laparoscopic cholecystectomy: results of first 300 cases in Hong Kong.
AB  - Prospective analysis of the first three hundred patients who underwent
      laparoscopic cholecystectomy was carried out in three surgical centres of Hong
      Kong. Over a 20-month period, 300 consecutive patients were recruited, including
      elective and emergency cases. The indications for laparoscopic cholecystectomy
      were symptomatic gallstones (78%), cholangitis (6%), pancreatitis (5%) and
      cholecystitis (11%). Patients with common duct stones (12) had preoperative
      endoscopic sphincterotomy and stone extraction prior to cholecystectomy.
      Laparoscopic cholecystectomy was accomplished successfully in 287 patients.
      Thirteen patients (4.3%) required conversion to open cholecystectomy. The reasons
      for conversion were: inability to identify cystic duct and common bile duct
      clearly (6); bleeding (5); Mirizzi syndrome (1); and slippage of cystic duct clip
      (1). The median operation time was 80 min with a range of 28-270 min. The median
      hospital stay was 3 days. Seventy-five per cent of patients required only a
      single dose of pethidine injection. None of the patients required blood
      transfusion. The overall complication rate was 7%. These included mild cellulitis
      of the subumbilical wound (3%) and postoperative chest infection (3%). One
      patient developed subphrenic abscess which resolved on percutaneous drainage
      under ultrasound guidance. Iatrogenic injury to the common bile duct was seen in
      one patient who had an impacted stone at Hartmann's pouch. With adequate training
      laparoscopic cholecystectomy can be performed safely. The advantages over open
      cholecystectomy are less wound pain, better cosmesis and shorter convalescence.

PMID- 7515427
TI  - When to return to work following a routine inguinal hernia repair: are doctors
      giving the correct advice?
AB  - Recurrence of an inguinal hernia following routine repair is not influenced by
      the convalescent time off work. Advice on this interval off work should not be
      influenced by the type of hernia, or the physical content of the patient's
      occupation. To determine if this is the case a questionnaire was sent to the 32
      consultant surgeons and 487 general practitioners in the Nottingham district.
      They were asked when they advised males between 18 and 65 years of age to return
      to work following a routine hernia repair and what factors influenced this time
      interval. The median advised time off work (4-6 weeks) was longer than that
      proposed by earlier studies (3-4 weeks). The advice of only 4% of doctors was not
      influenced by other factors. The physical content of the patient's job and
      whether he was self-employed had most influence on the advice doctors gave on
      when to return to work. In conclusion most doctors are wrongly advising patients
      on when to return to work following an inguinal hernia repair.

PMID- 7515429
TI  - Immunoscintigraphy of primary colorectal cancers with indium-111 monoclonal
      antibody B72.3.
AB  - Immunoscintigraphy with CYT-103, an 111indium-labelled immunoconjugate of B72.3,
      was evaluated in 10 patients before surgery for suspected or biopsy-proven
      primary colorectal cancer. The imaging results were compared with computed
      tomography (CT) findings at surgery, histopathology and immunohistochemistry.
      There were no adverse reactions following the administration of 1.0 mg 111In-CYT
      103. Surgical and pathological findings identified 15 sites of disease (10
      primary and five metastatic) and all but one lesion (severe dysplasia) were
      malignant. CT detected nine of 14 sites of malignancy compared to 12 as
      identified by immunoscintigraphy. It failed to detect two primary lesions and one
      case of peritoneal metastasis, all of which were imaged by CYT-103. Both imaging
      modalities failed to detect two of three cases with lymph node metastases and the
      dysplastic lesion (true negatives). The results indicate that 111In-CYT-103
      imaging exhibits high sensitivity and specificity in the detection of primary and
      secondary lesions in patients with colorectal cancer.

PMID- 7515430
TI  - Bilateral endoscopic splanchnicectomy through a posterior thoracoscopic approach.
AB  - The technique of bilateral total splanchnicectomy performed through a posterior
      thoracoscopic approach is described. The advantages of this route include
      excellent visual exposure of the neural anatomy of the sympathetic and avoidance
      of single lung anaesthesia. The procedure was performed for the relief of
      intractable pain in patients with advanced pancreatic cancer (n = 3) and patients
      suffering from chronic pancreatitis (n = 5). Persistent relief of pain until
      death was obtained in the patients with pancreatic cancer (2, 4, 6 months). In
      patients with chronic pancreatitis, the benefit to date has varied with the
      severity of the disease. In two patients with severe advanced disease and
      previous percutaneous blocks, the relief of pain lasted only 3 and 5 weeks and
      both patients required resection for renewed intractable pain. In three patients
      with minimal change disease, relief of pain has been good in the short term
      (maximum follow-up of 8 months). Bilateral thoracoscopic total splanchnicectomy
      merits further evaluation in patients with pancreatic pain. No complications
      including hypotension have been encountered.

PMID- 7515428
TI  - An audit of case-load and work-load in a regional plastic surgery unit using
      intermediate equivalents: a one-year study.
AB  - Until March 1992, when it was transferred to St John's Hospital, Livingston, the
      Regional Plastic Surgery Service for Adults in the Lothians was based at Bangour,
      West Lothian. Plastic surgery for children continues to be provided by the same
      staff but at the Sick Children's Hospital in Edinburgh. With increasing interest
      in improving efficiency of care and audits several ways in which assessments can
      be done have been suggested. Case numbers alone may give a totally misleading
      impression of the amount and type of operative work carried out. By combining
      numbers with intermediate equivalent estimation a useful audit can be obtained.

PMID- 7515431
TI  - A novel and convenient method of delayed primary skin closure for grossly
      contaminated abdominal wounds.
AB  - We describe a new method of delayed primary closure for grossly contaminated
      abdominal surgical wounds, combining the reduced vulnerability to infection
      associated with delayed skin closure and the excellent cosmesis of subcuticular
      suture. The surgical technique is outlined and the results in nine patients with
      gross intra-abdominal sepsis reported.

PMID- 7515432
TI  - Primary bone tumours of the shoulder: an audit of the Leeds Regional Bone Tumour
      Registry.
AB  - An audit of the prospectively gathered data of the Leeds Regional Bone Tumour
      Registry found that primary bone tumours of the shoulder constituted 145 of 2039
      cases (7%). Seventy-five per cent of these occurred in the proximal humerus, 20%
      in the scapula and 5% in the outer half of the clavicle. Malignant and benign
      tumours were of equal overall frequency (73 vs 72) but the malignant lesions
      tended to occur in an older population (mean ages 43 years and 17 years
      respectively). Simple bone cyst was the commonest diagnosis in children,
      chondrosarcoma in the middle age group and osteosarcoma in the over-60s.
      Presenting symptoms were a poor guide to whether the lesion was malignant or not
      and the correct preoperative diagnosis was made only in a minority of cases. In
      134 cases the diagnosis made by the referring pathologist was confirmed by the
      Bone Tumour Registry but in 11 cases, the diagnosis was changed by the Tumour
      Registry and differed with important clinical implications. Bone tumour
      registries provide a valuable source of cumulative information about uncommon
      tumours and facilitate accurate diagnosis, teaching and research.

PMID- 7515433
TI  - An audit of prophylactic antibiotic prescribing patterns in orthopaedic practice.
AB  - As part of the regular monthly audit of orthopaedic practice in Sheffield the
      prescribing patterns of orthopaedic surgeons were evaluated by questionnaire.
      Staff questioned were consultant orthopaedic surgeons and surgeons in training.
      The questionnaire depicted two areas of prophylactic antibiotic use: prescribing
      patterns in primary total hip replacement and in a number of procedures for
      closed fractures. The responses were anonymous. The results showed a range of
      treatment regimes were being used, although everyone prescribed an appropriate
      antibiotic at the time of surgery in primary joint replacement. The number of
      postoperative doses varied from none to treatment for 1 week. 78% continue
      intravenous therapy for 24 h. Prescribing patterns were not so clearly defined in
      surgery for closed fractures. 13% prescribe no prophylaxis in hip fracture
      fixation while 16% would prescribe intravenous therapy for 24 h after closed
      Kirshner wiring of a metacarpal fracture. The discussion of the findings has
      enabled the introduction of guidelines which should lead to optimal patient care
      and use of resources.

PMID- 7515434
TI  - Meckel's diverticulum in exomphalos minor.
AB  - Fifty-four cases of exomphalos were reviewed. After the exclusion of five cases,
      seven out of 25 cases of exomphalos minor had co-existing Meckel's diverticulum
      compared with one out of 24 cases of exomphalos major. The high incidence of
      Meckel's diverticulum in exomphalos minor highlights the importance of surgical
      rather than manual reduction of the sac contents in order to exclude the presence
      of viscera from the sac before division. Also, the raised incidence of Meckel's
      diverticulum in general may well be due to a raised incidence in exomphalos minor
      in particular.

PMID- 7515435
TI  - Pain relief following tennis elbow release.
AB  - We studied the outcome of tennis elbow release in 27 patients at an average of
      29.6 months after surgery. We found that 44% of patients had obtained complete
      pain relief, 37% of patients experienced occasional pain and 19% of patients
      still experienced moderate pain. Pain relief was significantly better in those
      patients with the shorter duration of preoperative symptoms. We therefore
      conclude that surgery for tennis elbow should be employed at an earlier stage
      than is currently practised.

PMID- 7515436
TI  - Abdominal pain as a course of acute admission to hospital.

PMID- 7515437
TI  - Minilaparotomy cholecystectomy.

PMID- 7515438
TI  - Preoperative shaving: patient and surgeon preferences and complications for the
      Gillies incision.

PMID- 7515439
TI  - The management of cardiac trauma by general surgeons in non-cardiothoracic units.

PMID- 7515440
TI  - Small bowel tumours: a diagnostic challenge.
AB  - In a 20-year retrospective study of 43 patients having surgery for small bowel
      neoplasia in a district general hospital, the commonest pathologies were lymphoma
      (12), carcinoid (12) and adenocarcinoma (11). Malignant neoplasms occurred in 38
      patients presenting on average at 68 years of age. In 4 patients a synchronous
      gastrointestinal neoplasm was found. The average duration of symptoms was 11
      weeks for operated patients. In 31 patients the presentation was as a surgical
      emergency. Only 10 had imaging investigations prior to emergency presentation
      from which diagnostic information was obtained in 1 patient and helpful
      information in a further 4. The 5-year survival figures of patients with small
      bowel neoplasia were carcinoid (50%), lymphoma (27%) and adenocarcinoma (15%),
      reflecting the poor prognosis of these patients even after 'curative resection'.
      Patients with carcinoid tumours were the exception, as long-term survival was not
      unusual even without complete resection of all macroscopic disease.

PMID- 7515441
TI  - Cystic fibrosis gene update.

PMID- 7515442
TI  - 14 alpha,14' beta-[Dithiobis[(2-oxo-2,1-ethanediyl)imino]]bis (7,8
      dihydromorphinone) and 14 alpha,14' beta-[dithiobis[(2-oxo-2,1-
      ethanediyl)imino]]bis[7,8-dihydro-N-(cyclopropylmethyl)normorphinone]: chemistry
      and opioid binding properties.
AB  - 14 alpha,14' beta-[Dithiobis[(2-oxo-2,1-ethanediyl)imino]] bis(7,8
      dihydromorphinone) (TAMO) (13) was synthesized by condensing 14 beta-amino-7,8
      dihydromorphine (4) with acetylthioglycolyl chloride and hydrolyzing the
      resulting ester with mild base to give a mixture of the thiol 9 and the disulfide
      13. Chromatography of the mixture resulted in conversion of the bulk of the thiol
      9 to the disulfide 13 by air oxidation. The disulfide 13 was also prepared by
      condensing the tert-butyldimethylsilyl ether of 4 with the dithiodiglycolyl
      chloride and treating the resulting product with F- to give the desired product.
      The pure thiol 9 free of contamination with the disulfide was prepared by
      treating 13 with excess N-acetyl-L-cysteine and processing the reaction mixture
      without resorting to chromatography for purification. The corresponding N
      (cyclopropylmethyl) nor compound 15 was prepared from the silyl ether 6 and
      acetylthioglycolyl chloride followed by hydrolysis, treatment with F-, and air
      oxidation. Incubation of bovine striatal membranes with 13 and 15 resulted in
      wash-resistant inhibition of the binding of the mu-selective peptide [3H][D
      Ala2,(Me)Phe4,Gly(ol)5]-enkephalin (DAMGO). Incubation of membranes with mu but
      not kappa or delta ligands protected the mu binding sites from alkylation by 13
      and 15. The wash-resistant inhibition of mu opioid binding was partially reversed
      by the addition of the reducing reagent dithiothreitol (DTT). A Scatchard plot of
      the effect of 13 and 15 on [3H]DAMGO binding showed that these affinity ligands
      caused a marked decrease in the Bmax value without affecting the Kd value. The
      wash-resistant inhibition of binding, the reduction in the number of binding
      sites, the partial reversal of wash-resistant inhibition of binding by DTT, and
      previously observed long-term antagonism of mu opioid receptors in vivo support
      the conclusion that 13 and 15 bind covalently to the mu opioid receptor.

PMID- 7515443
TI  - Design and synthesis of side-chain conformationally restricted phenylalanines and
      their use for structure-activity studies on tachykinin NK-1 receptor.
AB  - Constrained analogues of phenylalanine have been conceptually designed for
      analyzing the binding pockets of Phe7 (S7) and Phe8 (S8), two aromatic residues
      important for the pharmacological properties of SP, i.e., L
      tetrahydroisoquinoleic acid, L-diphenylalanine, L-9-fluorenylglycine (Flg), 2
      indanylglycine, the diastereomers of L-1-indanylglycine (Ing) and L-1
      benz[f]indanylglycine (Bfi), and the Z and E isomers of dehydrophenylalanine
      (delta ZPhe, delta EPhe). Binding studies were performed with appropriate ligands
      and tissue preparations allowing the discrimination of the three tachykinin
      binding sites, NK-1, NK-2, and NK-3. The potencies of these agonists were
      evaluated in the guinea pig ileum bioassay. According to the binding data, we can
      conclude that the S7 subsite is small, only the gauche (-) probe [(2S,3S)-Ing7]SP
      presents a high affinity for specific NK-1 binding sites. Surprisingly, the
      [delta EPhe7]SP analogue, which projects the aromatic ring toward the trans
      orientation, is over 40-fold more potent than the Z isomer, [delta ZPhe7]SP. A
      plausible explanation of these conflictual results is that either the binding
      protein quenches the minor trans rotamer of [(2S,3S)-Ing7]SP in solution or this
      constrained amino acid side chain rotates when inserted in the protein. In
      position 8, the high binding affinities of [Flg8]SP and [(2S,3S)-Bfi8]SP suggest
      that the S8 subsite is large enough to accept two aromatic rings in the gauche (
      ) and one aromatic ring in the trans direction. Peptides bearing two
      conformational probes in positions 7, 8, or 9 led to postulate that S7, S8, and
      S9 subsites are independent from each other. The volumes available for side
      chains 7 and 8 can be estimated to be close to 110 and 240 A3, respectively. The
      large volume of the S8 subsite raises question on the localization of the SP
      binding site in the NK-1 receptor. If SP were to bind in the transmembrane
      domains, the cleft defined by the seven transmembrane segments must rearrange
      during the binding process in order to bind a peptide in an alpha-helical
      structure and at least one large binding subsite in position 8. Thus, indirect
      topographical analysis with constrained amino acids might contribute to the
      analysis of the receptor/ligand dynamics. Finally, this study demonstrates that a
      good knowledge of the peptidic backbone structure and a combination of
      constrained amino acids are prerequisites to confidently attribute the preferred
      orientation(s) of an amino acid side chain.

PMID- 7515444
TI  - Protective effect of galanin on behavioral deficits in experimental traumatic
      brain injury.
AB  - The magnitude of behavioral deficits in traumatic brain injury (TBI) has been
      shown to be partly related to alterations in the balance between excitatory and
      inhibitory neurotransmitter release. Previous studies have demonstrated that
      extracellular excitatory neurotransmitter concentrations dramatically increase
      following experimental TBI. We examined the effects of a neuromodulatory peptide,
      galanin (GAL), on behavioral morbidity, as measured by sensory motor and memory
      performance tasks, associated with experimental TBI in the rat. A single
      intraventricular injection of GAL (1.0 micrograms, n = 8 or 10.0 micrograms, n =
      10) or cerebrospinal fluid (CSF) vehicle (n = 10) was administered 5 minutes
      prior to central fluid percussion TBI in rats. Performance on sensory motor tasks
      was assessed prior to injury and for 5 days after TBI with beam-balance, beam
      walking, and rotarod tasks. Memory performance was assessed on days 11-15 after
      TBI with the Morris water maze. TBI produced significant motor and memory
      deficits in the CSF-treated group. GAL-treated rats had significantly less
      magnitude of deficits compared to CSF-treated rats on beam-balance, beam-walking,
      and rotarod performance. The 1.0 micrograms GAL dose produced slightly greater
      protection than the 10.0 micrograms GAL dose. Neither GAL dose affected body
      weight loss or Morris water maze performance. These results suggest that the
      physiologic effects of GAL may reduce certain components of TBI morbidity,
      possibly by modulating neuronal excitability.

PMID- 7515446
TI  - Genetic susceptibility of benign prostatic hyperplasia.
AB  - In an effort to provide new insight into the etiology of benign prostatic
      hyperplasia (BPH), an evaluation of genetic factors was performed. Recognizing
      that early age of onset is a marker for hereditary disease, we performed a case
      control study of men with early onset of significant BPH. Men in the youngest
      quartile (less than 64 years old) with a large prostate (greater than 37 gm.
      resected tissue) who underwent surgery for BPH were identified as case probands
      from 909 consecutive prostatectomies for BPH. Control probands, selected because
      of the ability to distinguish treatment for benign prostate disease from
      treatment for malignant prostate disease, were women whose spouses underwent
      radical prostatectomy during the same interval. Male relatives of men with early
      onset of BPH had a 66% cumulative lifetime risk of prostatectomy for BPH,
      compared to a 17% cumulative risk among control relatives (p = 0.001). A 4-fold
      increase in age-specific risk of prostatectomy for BPH was present among
      relatives of men who had undergone prostatectomy for BPH (p = 0.0003), while
      brothers of these affected cases had a 6-fold increase in risk (p = 0.0089)
      compared to controls. To determine the likelihood that genetic factors account
      for this familial aggregation of BPH, segregation analysis was done. Although the
      small sample size prevented rigorous exclusion of nongenetic models, direct
      comparison of mendelian and nongenetic models showed that mendelian transmission
      provided the best overall explanation of the observed familial aggregation. The
      optimal model suggested mendelian dominant inheritance of a gene associated with
      early age at onset of BPH. These findings identify family history of BPH as a
      risk factor for clinical BPH and suggest the presence of a predisposing gene in
      patients with early onset BPH. Evidence of dominant mendelian transmission of
      this allele provides a framework for genetic studies to characterize this gene
      and elucidate the development of BPH in general.

PMID- 7515445
TI  - The management of patients with nonseminomatous germ cell tumors of the testis
      with serologic disease only after orchiectomy.
AB  - Management of patients with nonseminomatous germ cell tumors of the testis who
      have persistently elevated serum tumor marker levels (alpha-fetoprotein and/or
      human chorionic gonadotropin) following orchiectomy and no clinical evidence of
      disease is controversial. We reviewed our experience with 15 such patients at our
      cancer center between March 1977 and November 1991. Group 1 (11 patients)
      underwent initial retroperitoneal lymph node dissection and group 2 (4 patients)
      received primary chemotherapy. All group 1 patients required subsequent
      chemotherapy for retroperitoneal disease or persistent marker elevation, whereas
      only 1 of the 4 who received primary chemotherapy required later surgery. We
      conclude that tumor marker elevation in this setting is usually indicative of
      systemic tumor, which is best treated primarily by initial chemotherapy.

PMID- 7515447
TI  - Comparison of prostate specific antigen with prostate specific antigen density
      for 3 clinical applications.
AB  - We compared prostate specific antigen (PSA) to PSA density for 3 clinical uses:
      detection of nonpalpable prostate cancer, staging of clinically localized
      prostate cancer and prediction of PSA detectability following radical
      prostatectomy. Of 153 men with normal digital rectal examinations undergoing
      prostate biopsy 25% had prostate cancer. Analysis of receiver operator
      characteristic curves demonstrated that PSA density predicted the outcome of
      biopsy significantly better than did PSA (p = 0.0013). Pathological examination
      of 155 radical prostatectomy specimens revealed that 56% had pathologically
      uncontained disease. There was no difference between the ability of PSA and PSA
      density to predict the pathological findings (p = 0.2379). PSA data more than 1
      year postoperatively were available in 96 of the 155 prostatectomy patients. Of
      these men 41% had postoperative PSA levels of 0.1 ng/ml. or more. Preoperative
      PSA and PSA density values were almost identical in the ability to identify these
      patients (p = 0.6776). While PSA density is superior to PSA for the detection of
      prostate cancer in patients with a palpably normal prostate, it does not offer
      any improvement over PSA for staging of prostate cancer or for the prediction of
      PSA detectability after radical prostatectomy.

PMID- 7515448
TI  - Tumor volume and stage in carcinoma of the prostate detected by elevations in
      prostate specific antigen.
AB  - We reviewed the surgical specimen from 142 men undergoing radical prostatectomy
      for prostate cancer detected because of an elevation in serum prostate specific
      antigen alone. No patient had a palpable abnormality suggestive of cancer. One
      patient had no identifiable tumor in the radical prostatectomy specimen, 8 (6%)
      had only a few high power microscopic fields showing cancer, 40 (28%) had an
      estimated tumor volume of less than 1 cc and 93 (65%) had a tumor volume of
      greater than 1 cc. Surgical margins were positive in 37 patients (26%) and
      negative in 105 (73%). Most patients with cancer detected because of modest
      elevation in prostate specific antigen, even without palpable abnormalities, have
      a clinically significant tumor volume and are good candidates for radical
      prostatectomy.

PMID- 7515450
TI  - Re: The use of prostate specific antigen, clinical stage and Gleason score to
      predict pathological stage in men with localized prostate cancer.

PMID- 7515449
TI  - Prostate cancer: if we only had more data.

PMID- 7515451
TI  - Residual retroperitoneal mass following chemotherapy for infantile yolk sac
      tumor.
AB  - A child treated with chemotherapy for disseminated yolk sac tumor had a residual
      retroperitoneal mass after normalization of serum alpha-fetoprotein. The mass was
      excised and histologically showed only fibrous tissue, necrosis and
      calcification. To our knowledge this is the first case reported of a prepubertal
      yolk sac tumor associated with a residual retroperitoneal mass.

PMID- 7515452
TI  - Quantitation of NM23 expression in human prostate tissues.
AB  - The NM23 gene family (nm23-H1 and nm23-H2) has been reported as a measure of
      metastatic potential. The goal of this study was to discriminate nm23-H1 and nm23
      H2 gene expression in benign and malignant human prostate tissue and to determine
      the relationship of their expression to tumor stages. Specimens included 5 benign
      prostatic hyperplasias (BPH), 11 primary prostate adenocarcinomas (CaP) (5 stage
      B, 5 stage C and 1 stage D1), 2 pelvic lymph nodes with metastases and 3 prostate
      cancer cell lines derived from metastatic lesions. Polymerase chain reaction
      analysis of mRNA (RNA/PCR) was used to amplify transcripts of both NM23 genes and
      a normalizing gene (c-N-ras) to determine the relative levels of expression. A
      significant difference was shown between the BPH specimens and the cell lines
      from metastatic prostate cancer for nm23-H2 expression (p = 0.037) and the nm23
      H1/nm23-H2 gene expression ratio (p = 0.037). The nm23-H1/nm23-H2 ratio increased
      significantly (p = 0.026, tau-b = 0.377) from BPH, through the CaP stages, to the
      cell lines. The expression of nm23-H2 decreased significantly (p = 0.002, tau-b =
      -0.517) from BPH, through the CaP stages, to the cell lines. Thus, while nm23-H2
      appears to be significant for characterizing stages of CaP, an understanding of
      the metastatic phenotype will require further analysis of both NM23 genes.

PMID- 7515453
TI  - [Clinical evaluation of combined use of miconazole and G-CSF on deep-seated
      mycoses in patients with gynecological cancers].
AB  - A combined therapy using miconazole (MCZ) and G-CSF was evaluated in clinical
      patients who developed deep-seated mycoses and fever of unknown etiology
      following chemotherapy for malignant gyneco-obstetrical tumors. 1. Combined
      administration of 100 to 250 micrograms/day of G-CSF, 400 to 800 mg/day of MCZ,
      and various antibiotics (Group I) was evaluated in 7 patients with mycoses
      (fungemia and fungal infections of the digestive and respiratory systems). The
      efficacy of the treatment was found to be 3/3. When 200 to 1,200 mg/day of MCZ
      was combined with various antibiotics (Group III), the therapy was found to be
      slightly effective (2/4). The rate of fungal eradication was 3/5. 2. The efficacy
      of combined administration of 400 to 800 mg/day of MCZ, 100 to 250 micrograms/day
      of G-CSF, and various antibiotics (Group II) in patients with fever of unknown
      etiology (n = 8) was 4/4. The efficacy of combined administration of 400 to 800
      mg/day of MCZ and various antibiotics (Group III) was 3/4. 3. Leukocyte counts
      were recorded in the 7 patients who had received G-CSF (Groups I and II). The
      counts rose from < 1,000/microliters before the chemotherapy to >
      5,000/microliters in 6 patients (6/7) in 5 to 8 days following drug
      administration. The favorable clinical efficacy was recorded in all who received
      MCZ and antibiotics. 4. The objective or subjective adverse effects of this
      therapeutic modality were limited to mild nausea in a single case. No deviations
      from norm were noted in clinical or other tests.

PMID- 7515454
TI  - Adjuvant interferon in melanoma.

PMID- 7515455
TI  - Intracellular calcium and myosin light chain phosphorylation during U46619
      activated vascular contraction.
AB  - We investigated the relationship between [Ca2+]i, myosin light chain (LC20)
      phosphorylation and isometric force in guinea pig aortic strips during
      contractions activated by a thromboxane A2 analogue, (15S)-hydroxy-11 alpha,9
      alpha-(epoxymethano)prosta-5Z, 13E-dienoic acid (U46619). Isometric force and
      [Ca2+]i were measured simultaneously using preloaded aequorin as the
      intracellular calcium indicator. LC20 phosphorylation levels were determined by
      two dimensional polyacrylamide gel electrophoresis in parallel preparations.
      Contractions induced by U46619 were accompanied by increases in [Ca2+]i and LC20
      phosphorylation. The chelation of extracellular calcium with 2.5 mM EGTA
      significantly inhibited U46619-induced increases in [Ca2+]i, isometric force and
      LC20 phosphorylation. Steady-state force assumed a similar dependence on LC20
      phosphorylation for contractions stimulated by potassium depolarization, alpha 1
      adrenergic agonist phenylephrine and U46619 either in the presence or absence of
      extracellular calcium. On the contrary, the [Ca2+]i/force relation revealed that
      both U46619 and phenylephrine stimulated greater isometric force at lower [Ca2+]i
      than did KCl depolarization. The addition of a protein kinase C inhibitor, 1-(5
      isoquinolinylsulfonyl)-2-methylpiperazine (H-7), decreases force without
      significantly affecting either [Ca2+]i or LC20 phosphorylation levels. These
      results suggest that in guinea pig aortic smooth muscle U46619 increases the
      calcium sensitivity of the contractile apparatus but does not change the LC20
      phosphorylation/force relation in comparison to K+ depolarization. Protein kinase
      C is activated during U46619-stimulated contraction and might be involved in
      mechanisms other than LC20 phosphorylation.

PMID- 7515456
TI  - Hypervolemia and cycling time trial performance.
AB  - Ten experienced cyclists rode three simulated time trials to determine whether
      hypervolemia was associated with improvements in cycling time trial performance.
      The conditions were: exercise-induced hypervolemia (ExH), dextran-induced
      hypervolemia (DxH), and euvolemia (Eu). ExH was induced by 3 d of submaximal
      cycling lasting an average of 92.9 min at an average relative intensity of 68%.
      DxH was induced by acute plasma volume expansion with 400 +/- 121 ml of a 6%
      dextran solution. Compared with Eu, ExH and DxH were associated with 9.4% and
      8.7% elevations in blood volume as well as 11.1% and 12.4% elevations in plasma
      volume, respectively. Performance was significantly improved (P < 0.05) (i.e.,
      target work goal reached earlier) during ExH (81.41 +/- 5.52 min) and DxH(81.36
      +/- 5.06 min) than during Eu (90.87 +/- 5.27 min). Average power was
      significantly higher during E x H (246 +/- 13 W) and DxH (245 +/- 14 W) than
      during Eu (221 +/- 15 W). There were no significant differences in performance
      time or average power between the two hypervolemic conditions. Average sweat
      rates were significantly elevated during ExH (22.6 +/- 1.4 ml.min-1) and DxH
      (22.2 +/- 1.6 ml.min-1) than during Eu (20.4 +/- 1.7 ml.min-1). Rectal
      temperatures rose from approximately 37.2-39.2 degrees C during each time trial
      but there were no significant differences in T(re) between trials. In conclusion,
      hypervolemia, whether induced by short-term training or dextran-infusion, had a
      beneficial effect on performance and average power during simulated time trials
      lasting approximately 90 min. These improvements in performance were related to
      hypervolemia rather than other short-term training adaptations.

PMID- 7515458
TI  - Transcapillary escape rate of albumin positively correlates with plasma albumin
      concentration in acute but not in chronic inflammatory disease.
AB  - The relationship among "negative" plasma acute-phase proteins (APP), ie, albumin,
      prealbumin, and transferrin, and "positive" APP, ie, C-reactive protein (CRP),
      fibrinogen, and orosomucoid, was investigated in patients with acute infectious
      disease (n = 8) and in patients with chronic malignant disease (n = 9). In
      addition, the transcapillary escape rate (TER) and outflux (J(alb)) of albumin
      were investigated using an intravenous injection of 2 microCi 125I-albumin.
      Interleukin-6 (IL-6) plasma concentrations were measured with an enzyme
      immunoassay. In the majority of patients, negative APP were decreased, whereas
      positive APP were increased. However, in patients with infectious disease, there
      were no significant correlations between any of the negative and positive APP.
      Also, in patients with infectious disease, TER was increased to 8.6 +/- 3.4%/h
      (mean +/- SD), and J(alb) to 114 +/- 60 mg/kg/h, compared with normal values of
      4.3 +/- 2.6%/h and 108 +/- 7 mg/kg/h, respectively. Unexpectedly, there was a
      significant positive correlation between plasma albumin and both TER (r = .8279,
      P = .011) and J(alb) (r = .8683, P = .005). In patients with malignomas,
      significant correlations within negative and positive APP and inverse
      correlations between negative and positive APP resulted. Malignant disease
      induced only a slight elevation in TER (6.6 +/- 2.4%/h), J(alb) was within normal
      limits (92 +/- 35 mg/kg/h), and no correlations between plasma albumin
      concentrations and TER (r = -.0174, P = .97) or J(alb) (r = .4090, P = .27) were
      found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515457
TI  - [Parasites found in HIV-seropositive patients].
AB  - For 41 months, the presence of parasites was investigated in a seropositive HIV
      population with the clinical characteristics of stages 3 and 4 according to the
      OMS classification; of 212 fecal samples belonging to 135 patients which were
      analyzed, 53.33% presented enteroparasites. A direct parasitological exam and a
      Ritchie concentration were performed on the feces collected in formol 10%. Two
      smears were stained with Safranine 1% and two with modified Ziehl-Nielsen to
      identify Cryptosporidium sp. The detected frequencies were: Cryptosporidium The
      detected frequencies were: Cryptosporidium sp. 11.11%; I. belli 2.96%; G. lamblia
      11.85%; B. hominis 26.66%; A. lumbricoides 2.96%; E. vermicularis 1.48%; H. nana
      0.74%; E. coli 13.33%; E. nana 5.93%; Ch. mesnilii 2.22% and I. butschlii 0.74%.
      There were 46 monoparasitized patients, 19 biparasitized, 5 triparasitized and 2
      tetraparasitized. Furthermore, 17 bronchoalveolar lavages (BAL) and 194 sputa
      were processed, collected in formol 10% and centrifuged to exhaustion; 10 smears
      were prepared with sediment and were stained with toluidine blue. Groccot
      (Gomori) coloration was used to confirm doubtful cases. In 47% of the BAL and in
      22,68% of the sputa P. carinii was diagnosed. This represents 34.68%. The
      percentage of positive cases was: 30.88% for those patients who sent a single
      sputum, 36.84% for those who sent more than one and 27.27% for BAL. Finally, in 7
      patients who sent BAL and sputa, there were 2 positive and 2 negative cases in
      both materials, while P. carinii was diagnosed in 3 patients only in their BAL.

PMID- 7515459
TI  - A new society of palliative medicine.

PMID- 7515460
TI  - Wanted: guidelines for "palliative" anti-cancer drug use.

PMID- 7515461
TI  - Ophthalmology quiz #4: age related macular degeneration.

PMID- 7515463
TI  - Cross-resistance to heavy metals in hydrogen peroxide-resistant CHO cell
      variants.
AB  - Hydrogen peroxide-resistant Chinese hamster ovary (CHO) cells displayed cross
      resistance to CdCl2, HgCl2 and NaAsO2 but not to Na2Cr2O7, ZnCl2, NiCl2 and
      CuSO4. Resistance to hydrogen peroxide and to the metals was partially retained
      by these cells for many generations despite growth in drug-free medium. The loss
      of resistance was a slow process, and was different for the various metal
      compounds. Cell variants had a slightly higher content of non-protein
      intracellular thiols (NPSH) than sensitive cells. This biochemical feature did
      not seem to be the cause of resistance to CdCl2 but accounted for at least part
      of the resistance to HgCl2 and NaAsO2. Increased metallothionein synthesis did
      not seem to be responsible for the metal-resistant phenotype. These results
      suggest that resistance to specific metal compounds in cultured mammalian cells
      adapted to hydrogen peroxide is dependent on a number of factors which differ for
      the various metal compounds and which are characterized by a different stability.

PMID- 7515464
TI  - Cytogenetic adaptive response with multiple small X-ray doses in mouse germ cells
      and its biological influence on the offspring of adapted males.
AB  - Cytogenetic adaptive response of mouse germ cells was studied by exposing male
      mice to a sequence of 4 conditioning doses of 0.05 Gy each (D1) administered at
      10-day intervals and subsequently to a single challenging dose of 1.5 Gy (D2). In
      concurrent experiments, male mice after treatment with D1 doses alone were mated
      to unirradiated females and the F1 males were given the D2 dose. Chromosomal
      aberrations in both spermatocytes and bone-marrow cells and UV-induced UDS in
      splenocytes of these mice were studied. Adapted mice (i.e., D1 + D2 exposures)
      responded with a significantly lower frequency of chromosomal aberrations than
      the non-adapted (D2 exposure only) controls. The relative reduction in
      frequencies was, however, similar to that observed in earlier work with a single
      conditioning dose of 0.05 Gy. The frequencies of chromosomal aberrations in
      spermatocytes and bone-marrow cells as well as the levels of UV-induced UDS in
      splenocytes of the F1 males in the group D1 to fathers + D2 to F1 males were the
      same as those in F1 males which received only the D2 exposure.

PMID- 7515462
TI  - A ribosomal frameshifting error during translation of the argI mRNA of
      Escherichia coli.
AB  - Using fusions between the Escherichia coli genes argI and lacZ, it has been
      demonstrated that ribosomal frameshifting occurs at a frequency of between 3% and
      16% within the argI mRNA, soon after the initiation codon. The frameshift
      involves a phenylalanyl-tRNA shifting into the +1 frame at the sequence UUU-U/C.
      The shift does not occur if the in-frame phenylalanine codon UUU is replaced by
      UUC. The level of frameshifting is higher in dense cultures and is not dependent
      on phenylalanine starvation. In the wild-type argI gene this frameshifting event
      would be an error, leading to a truncated, non-functional protein. Therefore, it
      is unlike the numerous examples of required frameshifting events that have been
      described in other genes.

PMID- 7515465
TI  - Chromosome studies in Alzheimer's disease patients: distribution of dicentric
      breakpoints in lymphocytes irradiated in vitro.
AB  - A previous study showed a significant increase in dicentric frequency in
      lymphocytes irradiated in vitro from non-familial Alzheimer's disease patients
      compared to normal age-matched controls. This study examined the distribution of
      the chromosome breakpoints involved in the dicentric formation and found a non
      specific increase in all chromosomes.

PMID- 7515466
TI  - Refractory ceramic fibers (RCFs) induce germline aneuploidy in Drosophila
      oocytes.
AB  - Mineral fibers are ubiquitous in the natural environment and are widely used in
      industry in such applications as insulators. We have previously shown that
      asbestos fibers induce aneuploidy in oocytes of Drosophila melanogaster; here we
      extend those studies by testing refractory ceramic fibers (RCFs) for their
      mutagenicity to germ cells. The results establish that the tested RCFs are
      inducers of aneuploidy following feeding of adult females. A subset of the RCFs
      were also effective following larval feeding. Our results suggest that RCFs, like
      certain asbestos fibers, may pose a hazard to germ cells.

PMID- 7515467
TI  - Induction of micronuclei in cultured human lymphocytes treated with vinblastine
      before and after mitogen stimulation.
AB  - The analysis of micronuclei (MN) in cultured human lymphocytes can, in principle,
      detect exposure to clastogens and aneuploidogens alike. As aneuploidogens such as
      spindle poisons usually act on dividing cells, it is not clear how an in vivo
      exposure of resting peripheral lymphocytes to an aneuploidogen could be
      transmitted and expressed as MN in cultured lymphocytes. This question is
      fundamental in judging if cultured lymphocytes can be used to detect in vivo
      exposure to aneuploidogens. In the present study, in vivo exposure of resting
      lymphocytes to an aneuploidogen was simulated in vitro by a 24-h pulse treatment
      of human lymphocytes with vinblastine sulfate (VBL) before mitogen stimulation,
      followed by two washes and culture in the presence of phytohemagglutinin (PHA)
      for 72 h. This treatment protocol did result in an increased MN frequency, but
      only at the highest concentration of VBL available for analysis (100 ng/ml). A
      more effective response, with a significant effect already at 40 ng/ml, was
      obtained when the 24-h pulse treatment was started at 24 h of PHA-stimulated 72-h
      cultures. Still much lower concentrations of VBL (1 or 2.5 ng/ml) were effective,
      when the treatment, started 24 h after culture initiation, was continued for 48
      or 72 h (respectively) until cell harvest. These results demonstrate that MN
      induction by VBL depends, as expected, on the duration and timing of exposure,
      reflecting the availability of dividing cells during the treatment. The positive
      MN response obtained in the pulse-treated unstimulated lymphocytes may reflect an
      effect initiated in the resting stage and retained until mitosis or residual VBL
      left in the cells or in the cell suspension, despite the washes.

PMID- 7515468
TI  - Low doses of gamma-rays can induce the expression of mdr gene.
AB  - We reported earlier that human cervical carcinoma HeLa cells exposed to 30
      fractions of 0.5 Gy gamma-rays became resistant to cisplatin, methotrexate and
      vincristine, but retained the same sensitivity to gamma-rays and ultraviolet
      light. The aim of this study was to examine whether a small number of gamma-ray
      fractions, with a lower daily dose, may also change the sensitivity of
      preirradiated cells to different cytotoxic drugs. Using the modified MTT staining
      procedure, we found that cells preirradiated with 5 or 10 daily fractions of only
      0.17 Gy gamma-rays did not alter their sensitivity to mitomycin, cisplatin,
      methotrexate, 5-fluorouracil, etoposide and doxorubicin. However, 10 fractions of
      gamma-rays induced resistance to vincristine and vinblastine. Our
      immunocytochemical experiments using monoclonal antibody JSB-1 show that the
      plasma membrane P-glycoprotein is involved in the induced resistance to Vinca
      alkaloids.

PMID- 7515469
TI  - Microbial mutagenicity and in vitro chromosome aberration induction by FK973, a
      new antitumor agent.
AB  - The genotoxic activity of a new antitumor agent, FK973, was compared with that of
      mitomycin C (MMC) in eukaryotic and prokaryotic cells. In chromosome aberration
      tests using Chinese hamster fibroblast Don cells, FK973 induced a dose-related
      increase of aberrant cells after 6 h-pulse treatments, and the minimum effective
      concentrations with and without S9 were 0.625 and 0.0625 micrograms/ml,
      respectively. The compound increased revertant colonies in Salmonella typhimurium
      TA102 at the dose range of 10-5000 micrograms/plate with S9. Without S9, FK973
      induced a small increase at the dose range of 500-5000 micrograms/plate in two of
      three independent experiments, but the number of revertant colonies was less than
      double that of the vehicle control. The compound did not induce any revertant
      colonies in colonies in S. typhimurium TA100, TA98, TA1535 or TA1537 with or
      without S9. MMC was confirmed to increase both chromosome aberrations in Don
      cells and revertant colonies in TA102. The minimum clastogenic and mutagenic
      concentrations without S9 were 0.0156 microgram/ml and 0.005 microgram/plate,
      respectively. The results indicate that FK973 needs metabolic activation to
      induce reverse mutation in prokaryotic cells, but caused chromosome aberrations
      in mammalian cells without added S9.

PMID- 7515470
TI  - Effects of cinnamaldehyde on survival and formation of HGPRT- mutants in V79
      cells treated with methyl methanesulfonate, N-nitroso-N-methylurea, ethyl
      methanesulfonate and UV light.
AB  - The effects of the antimutagenic flavoring cinnamaldehyde on the induction of
      HGPRT- mutants by methyl methanesulfonate (MMS), N-nitroso-N-methylurea (MNU),
      ethyl methanesulfonate (EMS) and UV light was investigated in the Chinese hamster
      V79 cell line. Cinnamaldehyde did not show any mutagenic or toxic effects in this
      experimental system by itself and did not modify mutation frequency when given to
      cells simultaneously with chemical mutagens. Under these conditions, the
      cytotoxicity of MMS, but not that of MNU and EMS, was increased. Cell viability
      was also reduced in MNU-, EMS-, or UV light-pretreated cells when they were
      postincubated in the presence of cinnamaldehyde. Moreover, cinnamaldehyde reduced
      the frequency of mutations induced by MMS but not by the other mutagens. The
      results obtained suggest that cinnamaldehyde inhibits some cellular function(s)
      promoting the repair of a variety of different cytotoxic lesions. At the same
      time, stimulation by cinnamaldehyde of an error-free DNA repair mechanism acting
      on MMS-induced mutagenic damage was indicated.

PMID- 7515471
TI  - Increase of micronucleus frequency in cultured rat hepatocytes treated in vitro
      with benomyl and pirimiphos-methyl separately and in mixture.
AB  - The pesticides benomyl, a benzimidazole fungicide, and pirimiphos-methyl, an
      organophosphorus insecticide, were tested separately and in combination at a
      ratio of 6:1, a mixture frequently found in foodstuffs by residual analysis, to
      determine their possible genotoxic action. The effect was measured by the
      micronucleus test carried out on cultured rat hepatocytes stimulated to
      proliferate by epidermal growth factor (EGF). Adult rat hepatocytes were exposed
      in vitro for 48 h to the substances at increasing non-cytotoxic doses, chosen on
      the basis of cytotoxicity tests such as LDH and Neutral red assays. Benomyl
      induced a significant dose-related increase in micronucleus frequency; in
      contrast, pirimiphos-methyl was not genotoxic at any dose tested. When the
      hepatocytes were exposed to the two pesticides together at increasing doses, an
      enhancement in micronucleus frequency similar to that of benomyl alone was found,
      indicating that at this ratio and non-cytotoxic doses (up to 25 micrograms/ml
      benomyl + 4.2 micrograms/ml pirimiphos-methyl) no interaction occurs.

PMID- 7515472
TI  - Clastogenic effects of radiofrequency radiations on chromosomes of Tradescantia.
AB  - The clastogenicity of electromagnetic fields (EMF) has so far been studied only
      under laboratory conditions. We used the Tradescantia-micronucleus (Trad-MCN)
      bioassay in an in situ experiment to find out whether short-wave electromagnetic
      fields used for broadcasting (10-21 MHz) may show genotoxic effects. Plant
      cuttings bearing young flower buds were exposed (30 h) on both sides of a
      slewable curtain antenna (300/500 kW, 40-170 V/m) and 15 m (90 V/m) and 30 m (70
      V/m) distant from a vertical cage antenna (100 kW) as well as at the neighbors
      living near the broadcasting station (200 m, 1-3 V/m). The exposure at both sides
      of the slewable curtain antenna was performed simultaneously within cages, one of
      the Faraday type shielding the field and one non-shielding mesh cage. Laboratory
      controls were maintained for comparison. Higher MCN frequencies than in
      laboratory controls were found for all exposure sites in the immediate vicinity
      of the antennae, where the exposure standards of the electric field strength of
      the International Radiation Protection Association (IRPA) were exceeded. The
      results at all exposure sites except one were statistically significant. Since
      the parallel exposure in a non-shielding and a shielding cage also revealed
      significant differences in MCN frequencies (the latter showing no significant
      differences from laboratory controls), the clastogenic effects are clearly
      attributable to the short-wave radiation from the antennae.

PMID- 7515473
TI  - Lower mutation frequencies are induced by ENU in undifferentiated embryonic cells
      than in differentiated cells of the mouse in vitro.
AB  - The pluripotent embryonic carcinoma cells of line P19 established from
      undifferentiated cells of the early mouse embryo and their differentiated
      progeny, the epithelioid ectoderm-like EPI-7 cells, were investigated for the
      induction of mutations at the HPRT locus by the alkylating agent N-ethyl-N
      nitrosourea (ENU). We showed that the cytotoxic effects of ENU after a 5-h
      treatment were lower in undifferentiated P19 cells than in differentiated EPI-7
      cells. The IC50 values of ENU in the two cell lines amounted to 0.6 mg/ml and
      0.09 mg/ml for P19 and EPI-7 cells, respectively. The induction of 6-thioguanine
      resistant mutants by ENU (1.0 mg/ml) determined after an expression time of 8
      days for both cell lines resulted in similar mutation frequencies. Using
      expression times of 8 days for P19 and 11.75 days for EPI-7 cells, taking into
      account the longer generation time of differentiated EPI-7 cells (13.7 +/- 3.6 h)
      in comparison to undifferentiated P19 cells (9.3 +/- 0.9 h), ENU induced
      significantly higher mutant frequencies in EPI-7 cells (4865 mutants/10(6) cells)
      than in P19 cells (282 mutants/10(6) cells). Our results and data from the
      literature on UV irradiation-induced repair support the idea that the induction
      of lower mutation frequencies in embryonic cells may correlate with different
      proliferation capacities, cell cycle parameters and/or different mechanisms of
      DNA repair in embryonic stem cells and differentiated cells, respectively.

PMID- 7515474
TI  - Radioprotective effect of stobadine in the mouse micronucleus test.
AB  - Induction of micronuclei was studied 40 h post irradiation in peripheral blood
      reticulocytes of male mice treated or not with stobadine dipalmitate (70.07 mg/kg
      body weight) at two time intervals (2 h or 1 h) prior to and immediately after
      6.5 Gy 60Co exposure. A significant decrease of micronucleated reticulocytes was
      observed in the group of mice pretreated 2 h (P < 0.05) or 1 h (P < 0.01) before
      irradiation. 60Co irradiation followed by treatment with stobadine did not lead
      to the same protective effect in the micronucleus assay. It is therefore assumed
      that a radical-scavenging mechanism must be involved in radioprotection by
      stobadine.

PMID- 7515475
TI  - Mutagenicity of airborne particulates from combustion of electric cables in a
      waste metal retrieval area.
AB  - The disposal of massive quantities of synthetic materials has become a very
      serious environmental problem around the world. When synthetic polymers are burnt
      or smolder in air, the combustion products are extremely complex, often
      consisting of several hundred compounds. In Taiwan, a serious environmental
      problem was caused by the open air burning of discarded electric cords or cables,
      sheathed in polyvinyl chloride (PVC), in a special waste metal retrieval area.
      The resulting air pollution was especially severe. To determine mutagenicity, air
      samples were obtained from the area and the mutagenic compounds were purified by
      LH-20 column chromatography and semi-preparative HPLC. The active fractions
      purified at each step were monitored for their mutagenicity using S. typhimurium
      TA98. The major mutagenic fractions of the airborne particulate samples from the
      metal retrieval area were found to correspond to those of PVC smog generated from
      burning waste cables in a laboratory combustion chamber. Moreover, HPLC and
      fluorescence spectrometry showed 1,8-DNP and 1,6-DNP to be the major mutagenic
      compounds in the airborne particulate samples from the metal retrieval area.

PMID- 7515476
TI  - The infant or young child with developmental delay.

PMID- 7515477
TI  - The infant or young child with developmental delay.

PMID- 7515478
TI  - RNA. Life after transcription.

PMID- 7515479
TI  - Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long
      term depression.
AB  - Long-term potentiation (LTP) is a synaptic mechanism thought to be involved in
      learning and memory. Long-term depression (LTD), an activity-dependent decrease
      in synaptic efficacy, may be an equally important mechanism which permits neural
      networks to store information more effectively. One form of LTD that has been
      observed in the hippocampus requires activation of postsynaptic NMDA (N-methyl-D
      aspartate) receptors, a change in postsynaptic calcium concentration, and
      activation of postsynaptic serine/threonine protein phosphatase 1 (PP1) or 2A
      (PP2A). The mechanism by which PP1 or PP2A is regulated by synaptic activity is
      unclear because these protein phosphatases are not directly influenced by calcium
      concentration. LTD induction may require activation of a more complex protein
      phosphatase cascade consisting of the Ca2+/calmodulin-dependent protein
      phosphatase, calcineurin, its phosphoprotein substrate, inhibitor-1, and PP1. We
      tested this hypothesis using calcineurin inhibitors as well as different forms of
      inhibitor-1 loaded into postsynaptic cells. Our results suggest a signalling
      pathway in which calcineurin dephosphorylates and inactivates inhibitor-1. This
      in turn increases PP1 activity and contributes to the generation of LTD.

PMID- 7515480
TI  - SH2 domain specificity and activity modified by a single residue.
AB  - Many intracellular targets of protein-tyrosine kinases possess Src homology 2
      (SH2) domains that directly recognize phosphotyrosine-containing sites on
      autophosphorylated growth factor receptors and cytoplasmic proteins, and thereby
      mediate the activation of biochemical signalling pathways. SH2 domains possess
      relatively well conserved residues that form the phosphotyrosine-binding pocket,
      and more variable residues that are implicated in determining binding specificity
      by recognition of the three amino acids carboxy-terminal to phosphotyrosine (the
      +1 to +3 positions). One such residue, occupying the EF1 position of the +3
      binding pocket, is a Thr in the SH2 domain of the Src tyrosine kinase, but is
      predicted to be a Trp in the SH2 domain of the Sem-5/drk/Grb2 adaptor protein.
      Here we report that changing this residue in the Src SH2 domain from Thr to Trp
      switches its selectivity to resemble that of the Sem-5/drk/Grb2 SH2 domain.
      Furthermore, this mutant Src SH2 domain effectively substitutes for the SH2
      domain of the Sem-5 protein in activation of the Ras pathway in vivo. These
      results identify a residue that can modify SH2 selectivity, and indicate that the
      biological activity of an SH2 domain correlates with its binding specificity.

PMID- 7515481
TI  - Excitation-contraction uncoupling and muscular degeneration in mice lacking
      functional skeletal muscle ryanodine-receptor gene.
AB  - Contraction of skeletal muscle is triggered by the release of Ca2+ from the
      sarcoplasmic reticulum (SR) after depolarization of transverse tubules. The
      ryanodine receptor exists as a 'foot' protein in the junctional gap between the
      sarcoplasmic reticulum and the transverse tubule in skeletal muscle, and is
      proposed to function as a calcium-release channel during excitation-contraction
      (E-C) coupling. Previous complementary DNA-cloning studies have defined three
      distinct subtypes of the ryanodine receptor in mammalian tissues, namely skeletal
      muscle, cardiac and brain types. We report here mice with a targeted mutation in
      the skeletal muscle ryanodine receptor gene. Mice homozygous for the mutation die
      perinatally with gross abnormalities of the skeletal muscle. The contractile
      response to electrical stimulation under physiological conditions is totally
      abolished in the mutant muscle, although ryanodine receptors other than the
      skeletal-muscle type seem to exist because the response to caffeine is retained.
      Our results show that the skeletal muscle ryanodine receptor is essential for
      both muscular maturation and E-C coupling, and also imply that the function of
      the skeletal muscle ryanodine receptor during E-C coupling cannot be substituted
      by other subtypes of the receptor.

PMID- 7515482
TI  - Determination of the synthesis and uptake of alpha 2-macroglobulin by cultured
      human glioma cells.
AB  - Using immunological techniques, the synthesis of alpha 2-macroglobulin was
      studied in established cell lines derived from human glioblastomas multiforme.
      alpha 2-Macroglobulin was detected in cytoplasm and in the culture medium of the
      analyzed cell lines. Radioimmunoprecipitation revealed a protein with M(r)
      corresponding to alpha 2-macroglobulin in the medium conditioned by U-118MG and U
      343MG cells. On the other hand, using immunoblot analysis, alpha 2-macroglobulin
      was detected in all of the analyzed lines. In immunofluorescence test, alpha 2
      macroglobulin was determined also in all four cell lines, but with different
      staining pattern. Conditioned culture medium (CCM) of U-536MG cells with the
      lowest level of alpha 2-macroglobulin exerted the lowest mitogenic activity for
      human fibroblasts.

PMID- 7515483
TI  - Increase in the concentrations of brain serotonin and 5-hydroxyindoleacetic acid
      during growth of a transplanted murine lymphoma.
AB  - The concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic
      acid (5-HIAA) were studied in discrete brain areas of mice bearing transplantable
      Dalton's lymphoma (DL). Marked rise in 5-HT level (p < 0.05) was observed in
      serotonin secreting cell rich area--raphe region--as well as in hypothalamus and
      caudate putamen. High 5-HT level in these discrete areas was maintained
      throughout the period of tumor growth. Appreciable increase in 5-HT concentration
      was also observed in midbrain at the late stage (day 15 post-transplantation) of
      tumor growth. Unlike 5-HT, there was little change in 5-HIAA levels at the early
      stage (day 7) of tumor growth, and this was followed by a fall in 5-HIAA level
      around day 10 post-transplantation. However, the concentration of this 5-HT
      metabolite increased considerably at the late phase of tumor proliferation. The
      results suggest a close relationship between serotonin level in discrete brain
      regions and growth of an experimental tumor in mice.

PMID- 7515485
TI  - Characterization of the calcium influx induced by depolarization of guinea pig
      cochlear spiral ganglion cells.
AB  - We examined dynamic changes in intracellular calcium ion concentrations ([Ca2+]i)
      in isolated cochlear spiral ganglion cells (SGCs) of the guinea pig using digital
      imaging microscopy and the Ca(2+)-sensitive fluorescence dye fura-2. [Ca2+]i in
      SGCs was 83 +/- 22 nM (n = 50, means +/- SD) in cell somata at the resting state.
      Reversible increases in [Ca2+]i were elicited during membrane depolarization by
      high K+ (150 mM). This increase in [Ca2+]i was not observed under conditions of
      depolarization in Ca(2+)-free medium containing 1 mM EGTA. In addition, these
      increases in [Ca2+]i were sensitive to L-type calcium channel ligands, viz.,
      antagonized by nifedipine (50 microM), verapamil (10 microM) and enhanced by BAY
      K 8644 (1 microM). These observations suggest that increases in [Ca2+]i of
      cochlear SGCs induced by high K+ are due to an influx of extracellular Ca2+,
      probably through voltage-gated L-type calcium channels.

PMID- 7515486
TI  - Sudden deafness: a retrospective evaluation of dextran therapy.
AB  - A retrospective evaluation was performed in 112 patients treated during a 10-year
      period as inpatients with the diagnosis idiopathic sudden hearing loss. Excluding
      all patients in whom later other diagnosis were established, like Meniere's
      disease, collagenoses, mumps etc., 101 patients remained. 80 of them had been
      treated consistently according to a protocol as having idiopathic sudden hearing
      loss. These patients had all 5-day treatment with low molecular weight dextran
      and nicotinic acid and vitamin B during 1 month. 68% did completely recover or
      were markedly improved (> 30 dB), another 19% were fairly improved (10-30 dB).
      Statistical analysis showed that all retrocochlear signs or nystagmus made the
      prognosis less favorable. To wake up with the hearing loss was more favorable
      than a daytime debut. A mid-frequency loss had always a good prognosis. Because
      no untreated controls were included in the study, it was not possible to evaluate
      the specific effect of the treatment. The results obtained from this study have
      changed the treatment policy in our clinic.

PMID- 7515484
TI  - High cost medicines.

PMID- 7515487
TI  - Decongestion effect and rebound swelling of the nasal mucosa during 4-week use of
      oxymetazoline.
AB  - The aim of this study was to investigate whether long-term use of oxymetazoline
      induces a rebound swelling of the nasal mucosa and whether the decongestion
      effect is altered during medication. Eight healthy volunteers had oxymetazoline
      nasal spray (0.5 mg/ml; 0.1 ml in each nostril, three times daily) for 30 days
      and registrations of the mucosal surface positions were made using
      rhinostereometry. Compared to the registrations before the start of medication,
      no rebound swelling was registered after 10 days. After 30 days, however, a
      rebound swelling was registered in all subjects (p < 0.001). All of them, then,
      also reported nasal stuffiness. The decongested position of the nasal mucosa
      after one single dose of oxymetazoline was the same in the whole study. It is
      concluded that rhinitis medicamentosa develops after a relatively short time on
      oxymetazoline, even in healthy volunteers, and that the swelling probably is due
      to a vasodilatation rather than an edema. The study supports the recommendation
      that the drug should not be used over periods > 10 days.

PMID- 7515490
TI  - Long-term follow-up of the postoperative patient with congenital heart disease.
      General concerns.
AB  - There are an estimated 400,000 adults with postoperative congenital heart disease
      (CHD) in the United States. The majority of these patients require long-term
      follow-up for management of persistent problems. These problems are related to
      electrophysiologic sequelae, myocardial changes, ventricular failure, prosthetic
      materials, and infective endocarditis. The goal for adults with postoperative CHD
      is to achieve not only long-term survival, but the best possible quality of life.

PMID- 7515491
TI  - Care of the adult with cyanotic congenital heart disease.
AB  - In adults with cyanotic congenital heart disease (CHD), medical considerations
      apply to nonsurgical survivors and to postsurgical patients. The special needs of
      these groups present a unique challenge for the adult care practitioner. Clinical
      management revolves around the physiologic consequences of a right-to-left shunt.
      The care of the cyanotic CHD patient must encompass not only the physiologic
      variables that set these patients apart from the "typical" adult with acquired
      cardiovascular disease but also the lifelong psychosocial impact of their
      congenital heart program.

PMID- 7515488
TI  - Sequence-dependent effects in drug-DNA interaction: the crystal structure of
      Hoechst 33258 bound to the d(CGCAAATTTGCG)2 duplex.
AB  - The bis-benzimidazole drug Hoechst 33258 has been co-crystallized with the
      dodecanucleotide sequence d(CGCAAATTTGCG)2. The structure has been solved by
      molecular replacement and refined to an R factor of 18.5% for 2125 reflections
      collected on a Xentronics area detector. The drug is bound in the minor groove,
      at the five base-pair site 5'-ATTTG and is in a unique orientation. This is
      displaced by one base pair in the 5' direction compared to previously-determined
      structures of this drug with the sequence d(CGCGAATTCGCG)2. Reasons for this
      difference in behaviour are discussed in terms of several sequence-dependent
      structural features of the DNA, with particular reference to differences in
      propeller twist and minor-groove width.

PMID- 7515489
TI  - The binding site for ribosomal protein S8 in 16S rRNA and spc mRNA from
      Escherichia coli: minimum structural requirements and the effects of single
      bulged bases on S8-RNA interaction.
AB  - Through specific interactions with rRNA and mRNA, ribosomal protein S8 of
      Escherichia coli plays a central role in both assembly of the 30S ribosomal
      subunit and translational regulation of spc operon expression. To better
      understand S8-RNA association, we have measured the affinity of S8 for a number
      of variants of its rRNA and mRNA binding sites prepared by in vitro transcription
      or chemical synthesis. With the aid of site-directed deletions, we demonstrate
      that an imperfect, 33-nucleotide helical stem encompassing nucleotides 588-603
      and 635-651 possesses all of the structural information necessary for specific
      binding of S8 to the 16S rRNA. This segment consists of two short duplexes that
      enclose a conserved, asymmetric internal loop which contains features crucial for
      protein recognition. The S8 binding site in spc operon mRNA is very similar in
      both primary and secondary structure to that in 16S rRNA except for the presence
      of two single bulged bases in one of the duplex segments. In addition, the
      apparent association constant for the S8-mRNA interaction is approximately
      fivefold less than that for the S8-rRNA interaction. We show that the difference
      in affinity can be attributed to the effects of the bulged bases. Deletion of the
      bulged bases from the mRNA site increases its affinity for S8 to a level similar
      to that of the rRNA, whereas insertion of single-base bulges at equivalent
      positions within the rRNA site reduces its affinity for S8 to a value typical of
      the mRNA. Single-base bulges in the proximity of essential recognition features
      are therefore capable of modulating the strength of protein-RNA interactions.

PMID- 7515492
TI  - Solution structure of a core peptide derived from scyllatoxin.
AB  - An analysis of the sequences of scyllatoxin and charybdotoxin suggested that it
      would be possible to design a core peptide sequence which would still fold to
      give the beta-hairpin and helix seen in the toxins, but which would eliminate one
      disulfide and connecting residues. The core sequence was modeled, then
      synthesized and purified. The cysteines oxidize in air to give the same disulfide
      pairings as seen in the parent toxins as the major product. The three-dimensional
      structure of the core sequence peptide, termed Max, was determined using proton
      NMR spectroscopy and found to be identical in secondary structure to the toxins.
      However differences were found in the relative orientation of the beta-hairpin
      and helix. The use of this structural motif, found in many insect toxins, as a
      disulfide framework for exploring sequence/structure/activity relationships is
      discussed.

PMID- 7515493
TI  - Activation of JAK2 tyrosine kinase by prolactin receptors in Nb2 cells and mouse
      mammary gland explants.
AB  - One of the earliest cellular responses to prolactin (PRL) binding in Nb2 cells, a
      rat pre-T lymphoma cell line, is an increase in tyrosine phosphorylation of
      cellular proteins. In this work, immunologic techniques have been used to
      demonstrate that in Nb2 cells and in mouse mammary gland explants, JAK2, a non
      receptor tyrosine kinase, is activated following stimulation with PRL. PRL
      stimulated tyrosine phosphorylation of JAK2 at times as early as 30 sec and
      concentrations of PRL as low as 0.5 ng/ml (2.5 pM) in Nb2 cells and 100 ng/ml (5
      nM) in mammary gland explants. When JAK2 was immunoprecipitated from solubilized
      Nb2 cells or mammary gland explants and incubated with [gamma-32P]ATP, 32P was
      incorporated into a protein migrating with an apparent molecular weight
      appropriate for JAK2 only when cells had been incubated with PRL, indicating that
      JAK2 tyrosine kinase activity is exquisitely sensitive to PRL. In Nb2 cells, JAK2
      was found to associate with PRL receptor irrespective of whether or not the cells
      had been incubated with PRL. These results provide strong evidence that JAK2 is
      constitutively associated with the PRL receptor and that it is activated and
      tyrosine phosphorylated upon PRL binding to the PRL receptor. These results are
      consistent with JAK2 serving as an early, perhaps initial, signaling molecule for
      PRL.

PMID- 7515494
TI  - Reaction of diphtheria toxin channels with sulfhydryl-specific reagents:
      observation of chemical reactions at the single molecule level.
AB  - The diphtheria toxin channel is believed to be a homooligomer of its T domain in
      which each subunit consists of two alpha-helices, lying within the membrane,
      connected by a short interhelical loop of four amino acids (residues 349-352). To
      investigate the validity and implications of this model, we singly mutated each
      of these amino acids to cysteines, formed channels with the mutant T-domain
      proteins in planar lipid bilayers, and added to the trans compartment sulfhydryl
      specific reagents [methanethiosulfonate derivatives (MTS-ER)] that introduce a
      positive or negative charge to reacted cysteines. The introduction of a positive
      charge at residue 351 or 352 (through the MTS-ER reactions) resulted in a step
      decrease in single-channel conductance, whereas the introduction of a negative
      charge resulted in a step increase. The opposite sign of these effects indicates
      the predominantly electrostatic nature of the phenomenon and implies that
      residues 351 and 352 lie close to the channel entrance. The same reactions at
      residue 350 resulted in very little change in channel conductance but instead
      changed the character of the natural rapid flickering of the channel between open
      and closed states to one in which the channel spent more time in the closed
      state; this may have resulted from the group introduced at position 350 acting as
      a tethered channel blocker. The MTS derivatives had no effect on channels
      containing a cysteine at position 349, suggesting that this residue faces away
      from the channel entrance. We propose that the step changes in conductance or
      flickering pattern result from the chemical reaction of one MTS-ER molecule with
      one cysteine, and thus a bimolecular chemical reaction is being witnessed at the
      single molecule level. From the distribution of waiting times between the
      appearance (i.e., the opening) of a channel and the step change in its
      conductance or flickering pattern, we can calculate a pseudo-first-order rate
      constant, which can then be converted to a second-order rate constant, for the
      chemical reaction.

PMID- 7515495
TI  - Role of scatter factor in the pathogenesis of AIDS-related Kaposi sarcoma.
AB  - Kaposi sarcoma (KS) is a complex multicellular neoplasm that is commonly
      associated with AIDS. The pathogenesis of KS is not well understood. KS tumor
      cells grow poorly in vitro and require medium conditioned by retrovirus-infected
      T lymphocytes. We observed that conditioned medium (CM) from type II human T-cell
      leukemia virus (HTLV-II)-infected T cells (HTLV-II CM) induces conversion of
      endothelial cells (ECs) to a KS tumor cell-like phenotype. ECs grown in HTLV-II
      CM acquired a spindle-shaped morphology, the ability to express factor XIIIa and
      other KS cell markers, and a cytokine production profile similar to that of KS
      cells. We found that HTLV-II CM contains large quantities of scatter factor (SF),
      an angiogenic cytokine that stimulates cell motility. SF induced ECs to become
      spindle-shaped and express factor XIIIa. Moreover, SF was found to be a mitogen
      for KS cells in vitro and was identified within KS lesions in vivo. SF mRNA was
      present in KS cells in vitro, and antibodies against SF inhibited the growth of
      KS cells. The receptor for SF, the c-met protein, was expressed by ECs, dermal
      dendrocytes, and KS tumor cells in vitro and in vivo. HTLV-II CM was highly
      angiogenic in vivo, which was blocked by antibodies against SF. Based on these
      findings, we suggest that SF plays a role in the initiation and maintenance of KS
      lesions.

PMID- 7515497
TI  - Expression of cytokeratin confers multiple drug resistance.
AB  - The cytokeratin network is an extensive filamentous structure in the cytoplasm
      whose biological function(s) is unknown. Based upon previous data showing the
      modification of cytokeratin by mitoxantrone, we investigated the ability of
      cytokeratin networks to influence the survival response of cells to
      chemotherapeutic agents. We have compared the survival of mouse L fibroblasts
      lacking cytokeratins with that of L cells transfected with cytokeratins 8 and 18
      in the presence of chemotherapeutic drugs. The expression of cytokeratins 8 and
      18 conferred a multiple drug resistance phenotype on cells exposed to
      mitoxantrone, doxorubicin, methotrexate, melphalan, Colcemid, and vincristine.
      The degree of drug resistance was 5-454 times that of parental cells, depending
      upon the agent used. Drug resistance could not be attributed to altered growth
      characteristics, altered drug accumulation, or an altered drug efflux in the
      transfected cells. Cytokeratin does not confer resistance to ionizing radiation,
      which damages DNA independently of intracellular transport mechanisms. These data
      suggest a role for cytokeratin networks in conferring a drug resistance
      phenotype.

PMID- 7515498
TI  - Bicarbonate conductance and pH regulatory capability of cystic fibrosis
      transmembrane conductance regulator.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial
      Cl- channel regulated by protein kinase A. The most common mutation in cystic
      fibrosis (CF), deletion of Phe-508 (delta F508-CFTR), reduces Cl- secretion, but
      the fatal consequences of CF have been difficult to rationalize solely in terms
      of this defect. The aim of this study was to determine the role of CFTR in HCO3-
      transport across cell membranes. HCO3- permeability was assessed from
      measurements of intracellular pH [pHi; from spectrofluorimetry of the pH
      sensitive dye 2',7'-bis(2-carboxyethyl)-5-(and -6)carboxyfluorescein] and of
      channel activity (patch clamp; cell attached and isolated, inside-out patches) on
      NIH 3T3 fibroblasts and C127 mammary epithelial cells transfected with wild-type
      CFTR (WT-CFTR) or delta F508-CFTR, and also on mock-transfected cells. When WT
      CFTR-transfected cells were acidified (pulsed with NH4Cl) and incubated in Na(+)
      free (N-methyl-D-glucamine substitution) solutions (to block Na(+)-dependent pHi
      regulatory mechanisms), pHi remained acidic (pH approximately 6.5) until the
      cells were treated with 20 microM forskolin (increases cellular [cAMP]); pHi then
      increased toward (but not completely to) control level (pHi 7.2) at a rate of
      0.055 pH unit/min. Forskolin had no effect on rate of pHi recovery in delta F508
      and mock-transfected cells. This Na(+)-independent, forskolin-dependent pHi
      recovery was not observed in HCO3-/CO2-free medium. Forskolin-treated WT-CFTR
      transfected (but not delta F508-CFTR or mock-transfected) cells in Cl(-)
      containing, HCO3(-)-free solutions showed Cl- channels with a linear I/V
      relationship and a conductance of 10.4 +/- 0.5 pS in symmetrical 150 mM Cl-. When
      channels were incubated with different [Cl-] and [HCO3-] on the inside and
      outside, the Cl-/HCO3- permeability ratio (determined from reversal potentials of
      I/V curves) was 3.8 +/- 1.0 (mean +/- SEM; n = 9); the ratio of conductances was
      3.9 +/- 0.5 (at 150 mM Cl- and 127 mM HCO3-. We conclude that in acidified cells
      the WT-CFTR functions as a base loader by allowing a cAMP-dependent influx of
      HCO3- through channels that conduct HCO3- about one-quarter as efficiently as it
      conducts Cl-. Under physiological conditions, the electrochemical gradients for
      both Cl- and HCO3- are directed outward, so CFTR likely contributes to the
      epithelial secretion of both ions. HCO3- secretion may be important for
      controlling pH of the luminal, but probably not the cytoplasmic, fluid in CFTR
      containing epithelia. In CF, a decreased secretion of HCO3- may lead to decreased
      pH of the luminal fluid.

PMID- 7515496
TI  - p56lck-independent activation and tyrosine phosphorylation of p72syk by T-cell
      antigen receptor/CD3 stimulation.
AB  - Activation of resting T lymphocytes by ligands to the T-cell antigen receptor
      (TCR)/CD3 complex is initiated by rapid tyrosine phosphorylation of cellular
      proteins. Protein-tyrosine kinases (PTKs) of the src family are known to be
      important, but the mechanism of their recruitment and their interactions with
      PTKs of other families are incompletely understood. We show that a member of
      another family of PTKs, the p72syk kinase, is constitutively bound to the TCR/CD3
      complex and becomes tyrosine phosphorylated and activated within 1 min after
      TCR/CD3 stimulation. This activation did not depend on the presence of p56lck in
      T cells and in transfected COS cells. In both cases, however, the phosphorylation
      of cellular substrates was augmented by src family PTKs. We propose that p72syk
      may act as an immediate receptor-activated kinase upstream of the related p70zap
      PTK and the src family PTKs p56lck and p59fyn in T cells and that these src
      family PTKs act as signal amplifiers.

PMID- 7515499
TI  - A conserved heptamer motif for ribosomal RNA transcription termination in animal
      mitochondria.
AB  - A search of sequence data bases for a tridecamer transcription termination
      signal, previously described in human mtDNA as being responsible for the
      accumulation of mitochondrial ribosomal RNAs (rRNAs) in excess over the rest of
      mitochondrial genes, has revealed that this termination signal occurs in
      equivalent positions in a wide variety of organisms from protozoa to mammals. Due
      to the compact organization of the mtDNA, the tridecamer motif usually appears as
      part of the 3' adjacent gene sequence. Because in phylogenetically widely
      separated organisms the mitochondrial genome has experienced many rearrangements,
      it is interesting that its occurrence near the 3' end of the large rRNA is
      independent of the adjacent gene. The tridecamer sequence has diverged in
      phylogenetically widely separated organisms. Nevertheless, a well-conserved
      heptamer--TGGCAGA, the mitochondrial rRNA termination box--can be defined.
      Although extending the experimental evidence of its role as a transcription
      termination signal in humans will be of great interest, its evolutionary
      conservation strongly suggests that mitochondrial rRNA transcription termination
      could be a widely conserved mechanism in animals. Furthermore, the conservation
      of a homologous tridecamer motif in one of the last 3' secondary loops of
      nonmitochondrial 23S-like rRNAs suggests that the role of the sequence has
      changed during mitochondrial evolution.

PMID- 7515500
TI  - Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains.
AB  - The immunophilin-immunosuppressant complexes cyclophilin-cyclosporin A (CsA) and
      FKBP12-FK506 inhibit the phosphatase calcineurin to block T-cell activation.
      Although cyclophilin A, FKBP12, and calcineurin are highly conserved from yeast
      to man, none had previously been shown to be essential for viability. We find
      that CsA-sensitive yeast strains are FK506 hypersensitive and demonstrate that
      calcineurin is required for viability in these strains. Mutants lacking
      cyclophilin A or FKBP12 are resistant to CsA or FK506, respectively. Thus, both
      the immunosuppressive and the antifungal actions of CsA and FK506 result from
      calcineurin inhibition by immunophilin-drug complexes. In yeast strains in which
      calcineurin is not essential, calcineurin inhibition or mutation of calcineurin
      confers hypersensitivity to LiCl or NaCl, suggesting that calcineurin regulates
      cation transport.

PMID- 7515501
TI  - Two distinct signaling pathways trigger the expression of inducible nitric oxide
      synthase in rat renal mesangial cells.
AB  - The expression of nitric oxide synthase (NOS; EC 1.14.13.39) is induced in rat
      glomerular mesangial cells by exposure to the inflammatory cytokine interleukin 1
      beta (IL-1 beta) or cAMP-elevating agents. Stimulation with IL-1 beta alone leads
      to an approximately 40-fold increase in NOS activity and nitrite synthesis,
      whereas the elevation of cAMP with forskolin, cholera toxin, salbutamol, or
      dibutyryl-cAMP for 24 h resulted in a 2- to 12-fold increase in NOS activity.
      Moreover, the combinations of IL-1 beta with each of the cAMP-elevating agents
      greatly enhanced NOS activity in a synergistic fashion. Northern-blot analysis
      demonstrated a single band of approximately 4.5 kb for the NOS mRNA in rat
      mesangial cells. IL-1 beta increased NOS mRNA levels in a dose- and time
      dependent fashion with a peak of NOS mRNA at 24 h. Dibutyryl-cAMP also increased
      NOS mRNA levels in mesangial cells in a dose- and time-dependent manner.
      Furthermore, combination of IL-1 beta and forskolin revealed a strong synergy
      with maximal mRNA levels 12 h after stimulation. Nuclear run-on transcription
      experiments suggest that IL-1 beta and cAMP synergistically interact to increase
      NOS gene expression at the transcriptional level. Furthermore, message stability
      studies established that NOS mRNA induced by cAMP has a longer half-life than the
      IL-1 beta-induced message. Moreover, cAMP exposure markedly prolonged the half
      life of NOS mRNA from 1 h to 3 h. These data suggest that the level of NOS mRNA
      is controlled by at least two different signaling pathways, one involving cAMP
      and the other being triggered by cytokines such as IL-1 beta. The two pathways
      act synergistically and thus potently up-regulate the expression of inducible NOS
      in rat mesangial cells.

PMID- 7515502
TI  - Estradiol causes the rapid accumulation of cAMP in human prostate.
AB  - Androgens are widely acknowledged to be central to the pathogenesis of benign
      prostatic hypertrophy (BPH). However, BPH increases in prevalence as men age, at
      precisely the stage of life when plasma androgens are decreasing. The decrease in
      total plasma androgens is amplified by an age-related increase in plasma sex
      hormone-binding globulin (SHBG) that results in a relatively greater decrease in
      free androgens than in total androgens. In addition, estrogens have long been
      suspected to be important in BPH, but a direct effect on the human prostate has
      never been demonstrated. We present data that are consistent with a role for
      estradiol, and for a decrease in androgens and an increase in SHBG, in the
      pathogenesis of BPH. We show that estradiol, but not dihydrotestosterone, acts in
      concert with SHBG to produce an 8-fold increase in intracellular cAMP in human
      BPH tissue. This increase is not blocked by an antiestrogen and is not provoked
      by an estrogen (diethylstilbestrol) that does not bind to SHBG, thus excluding
      the classic estrogen receptor as being operative in these events. Conversely,
      dihydrotestosterone, which blocks the binding of estradiol to SHBG, completely
      negates the effect of estradiol. Finally, we demonstrate that the SHBG-steroid
      responsive second-messenger system is primarily localized to the prostatic
      stromal cells and not to the prostatic epithelial cells. Thus, we have shown a
      cell-specific, powerful, nontranscriptional effect of estradiol on the human
      prostate.

PMID- 7515503
TI  - Analysis of gene expression in the preimplantation mouse embryo: use of mRNA
      differential display.
AB  - The analysis of differential gene expression during preimplantation embryogenesis
      has been hindered by the paucity of biological material. We report modifications
      of the recently described mRNA differential display method (Liang, P. & Pardee,
      A. B. (1992) Science 257, 967-971) to analyze differential gene expression during
      mouse preimplantation development. The method detects the appropriate changes in
      the temporal pattern of expression of an amplicon that by DNA sequence analysis
      is the cytokeratin endo A, a gene whose temporal pattern of expression has been
      previously determined by S1 nuclease digestion. In addition, this method
      identifies amplicons that likely represent genes (i) that encode maternal mRNAs,
      (ii) that are products of early and late zygotic gene activation, (iii) whose
      expression is greatest during the eight-cell stage (i.e., expressed in a stage
      specific manner), and (iv) whose expression is greatest in the blastocyst. In
      addition to endo A, sequence analysis of these amplicons reveals that an amplicon
      that displays a temporal pattern of expression consistent with it being a
      maternal mRNA is the alpha subunit of the mitochondrial F1 ATP synthase.

PMID- 7515504
TI  - Expression and growth inhibitory effect of decapentaplegic Vg-related protein 6:
      evidence for a regulatory role in keratinocyte differentiation.
AB  - Decapentaplegic Vg-related protein 6 (DVR-6 or bone morphogenetic protein BMP-6)
      is a member of the DVR subgroup of the transforming growth factor beta
      superfamily, a large group of multifunctional signaling polypeptides that are
      expressed as secreted disulfide-bonded dimers proteolytically cleaved from larger
      precursors. The predominant expression of DVR-6 in the differentiating
      postmitotic layers of stratified squamous epithelia strongly suggests a role for
      DVR-6 in regulation of epithelial differentiation. In primary mouse keratinocytes
      induced to differentiate by suspension culture in methylcellulose, new expression
      of DVR-6 mRNA and protein was detected within 8 h among a majority of the
      suspended cells, which preceded the induction of expression of the suprabasal
      keratins K1 and K10. To test the hypothesis that DVR-6 is a keratinocyte growth
      regulatory factor, a retroviral expression vector expressing human DVR-6 was used
      to infect attached cultures of undifferentiated basal cells. Expression of DVR-6
      in primary mouse keratinocytes before differentiation resulted in the secretion
      of prepro and processed (pro region) forms in the conditioned medium and a
      dramatic inhibition of cell growth. These findings suggest that inhibition of
      cell growth by DVR-6 may be a primary step in keratinocyte differentiation.

PMID- 7515505
TI  - Heterogeneity of T-cell receptor alpha-chain complementarity-determining region 3
      in myelin basic protein-specific T cells increases with severity of multiple
      sclerosis.
AB  - The pathogenesis of multiple sclerosis (MS) is thought to involve a T-cell
      mediated autoimmune process. Experimental allergic encephalomyelitis (EAE), an
      animal model resembling MS, can be induced by immunization with myelin antigens
      such as myelin basic protein. The T-cell antigen receptor (TCR) usage in EAE is
      highly restricted in some strains of animals and experimental treatments
      targeting the TCR have been successful in EAE. Examination of the TCR beta-chain
      variable-region (V beta) usage of MBP-specific T-cell lines in MS patients has
      produced conflicting results. Our previous studies of TCR alpha-chain variable
      region usage in monozygotic twins demonstrated a general skewing of the TCR
      repertoire in individuals with MS. This skewing became apparent only after
      stimulation with antigens; in peripheral blood lymphocyte preparations from
      individuals with MS V alpha 8-bearing T cells were preferentially selected by
      stimulation with myelin basic protein. In the present study we examined
      complementarity-determining region 3 of those V alpha 8-positive TCRs. Marked
      sequence heterogeneity was found in all individuals with severe MS. In contrast,
      restricted areas of complementarity-determining region 3 were found in healthy
      control individuals and in individuals with a mild form of MS. Sequences from
      tetanus toxoid-specific V alpha 8-positive T cells generated from the same
      individuals were relatively homogeneous within individuals regardless of disease
      activity and were distinct from the sequences of complementarity-determining
      region 3 in myelin basic protein-stimulated lines. These findings suggest that
      disease severity may be associated with increased heterogeneity of myelin antigen
      specific T cells and could reflect an impaired ability of the immune system to
      down-regulate these anti-self responses.

PMID- 7515507
TI  - Prospective controlled studies of the behavioral and biological effects of
      exogenous corticosteroids.
AB  - The brain is an important target organ for both endogenous and synthetic
      corticosteroid hormones, but the nature of steroid action there is complex. We
      review a series of studies that was designed to elucidate possible relationships
      between the behavioral and biological effects of exogenous corticosteroids. In
      these studies, corticosteroids were administered to intact animals or to
      currently healthy volunteers, and behavioral and biological indices of
      corticosteroid effects were jointly assessed. In the first study, chronic
      corticosterone administration to intact rats resulted in increased locomotor
      activity (consistent with increased caudate or nucleus accumbens dopamine
      activity) and increased caudate homovanillic acid (HVA) levels. In the second
      study, acute dexamethasone administration to healthy human volunteers resulted in
      increased plasma HVA levels. These findings in animals and humans may help
      explain vulnerability factors for experiencing psychotic reactions during chronic
      corticosteroid treatment. To more closely mimic clinical conditions in which
      "steroid psychoses" develop, we administered a higher dose and more chronic
      corticosteroid medication (prednisone, 80 mg/day for 5 days) in a double-blind
      manner to healthy volunteers. Consistent with prior clinical observations,
      behavioral changes were variable across subjects. Seventy-five percent of the
      individual volunteers developed mild behavioral side effects during prednisone
      administration; in addition, significant, specific deterioration in cognitive
      performance was observed. Prednisone administration was also associated with
      significant decreases in plasma levels of adrenocorticotropic hormone (ACTH),
      cortisol, and 3-methoxy,4-hydroxyphenyl glycol (MHPG) and in cerebrospinal fluid
      (CSF) levels of ACTH, beta-endorphin (BE), beta-lipotropin (BLPH), somatostatin
      like immunoreactivity (SLI), and norepinephrine (NE). It was also associated with
      significant slowing of brain wave electrical activity (viz., an increase in theta
      wave activity) on quantitative electroencephalography. Several behavioral
      changes, particularly those relating to mood or cognition, were related to
      changes in CSF levels of NE, MHPG, ACTH, BE, BLPH, and SLI and to the slowing of
      brain wave activity. Our preliminary data raise the possibility that the
      behavioral effects of exogenous corticosteroids have specific neural concomitants
      and that the pattern of biological changes produced contributes to the behavioral
      variability observed. Steroid effects on levels of biogenic amines, pro
      opiomelanocortin (POMC)-related peptides and somatostatin, among others, as well
      as on brain electrophysiology, may be behaviorally relevant and are highlighted
      as being worthy of further investigation.

PMID- 7515506
TI  - Anti-peptidyl transferase leader peptides of attenuation-regulated
      chloramphenicol-resistance genes.
AB  - The chloramphenicol (Cm)-inducible cmlA gene of Tn1696 specifies nonenzymatic
      resistance to Cm and is regulated by attenuation. The first eight codons of the
      leader specify a peptide that inhibits peptidyl transferase in vitro.
      Functionally similar, but less inhibitory, peptides are encoded by the leaders of
      Cm-inducible cat genes. However, the cat and cmlA coding sequences are unrelated
      and specify proteins of unrelated function. The inhibition of peptidyl
      transferase by the leader peptides is additive with that of Cm. Erythromycin
      competes with the inhibitory action of the peptides, and erythromycin and the
      peptides footprint to overlapping sites at the peptidyl transferase center of 23S
      rRNA. It is proposed that translation of the cmlA and cat leaders transiently
      pauses upon synthesis of the inhibitor peptides. The predicted site of pausing is
      identical to the leader site where long-term occupancy by a ribosome (ribosome
      stalling) will activate downstream gene expression. We therefore propose the
      inducer, Cm, converts a peptide-paused ribosome to the stalled state. We discuss
      the idea that cooperativity between leader peptide and inducer is necessary for
      ribosome stalling and may link the activation of a specific drug-resistance gene
      with a particular antibiotic.

PMID- 7515509
TI  - A geometric approach to the analysis of physiological flow data.
AB  - Physiological flow data are common in various medical fields. Examples include
      urinary, blood and expiratory flows. They are widely used in assessing functions
      in the urinary, circulatory, or pulmonary systems, respectively. Current
      statistical methods for analysing these flow data in clinical trials are either
      univariate analyses, which do not utilize all the information together, or some
      conventional multivariate methods (such as regression analyses) which yield
      results that do not render clear medical interpretations. This paper presents a
      new approach to analysing the flow data, using urinary flow as the primary focus.
      The basic idea and technical steps are applicable to other flow data as well. 
      The proposed method aims to transform the flow measurements back to the shape of
      the flow graphs. Since the whole geometric pattern of the flow graph provides
      more information about the patient's flow condition than any individual flow
      parameter alone, the method is a meaningful way of combining and analysing the
      flow data in both statistical and clinical senses. The method is a three-stage
      procedure. Patients are classified into three classes in the first stage and then
      ranked in sequence in the second stage, according to the geometry of the shape
      pattern and some clinical criteria. The classification procedure is shown to be
      very reliable when compared with the clinician's visual evaluation, and hence can
      be implemented by computer programming to aid clinical trials involving many
      patients. The whole ranking score is then readily analysed at the third stage for
      comparing treatment effects by the analysis of covariance method based on ranks,
      with the post-treatment score as the response variable and the baseline score as
      the covariate. An example of a urinary flow data set is provided to illustrate
      the use of the procedure.

PMID- 7515511
TI  - [Stem cell factor: a novel multipotent growth factor for hematopoiesis].

PMID- 7515510
TI  - [Nitric oxide: a new important messenger molecule in the central nervous system].

PMID- 7515512
TI  - Structure of the equine infectious anemia virus Tat protein.
AB  - Trans-activator (Tat) proteins regulate the transcription of lentiviral DNA in
      the host cell genome. These RNA binding proteins participate in the life cycle of
      all known lentiviruses, such as the human immunodeficiency viruses (HIV) or the
      equine infectious anemia virus (EIAV). The consensus RNA binding motifs [the
      trans-activation responsive element (TAR)] of HIV-1 as well as EIAV Tat proteins
      are well characterized. The structure of the 75-amino acid EIAV Tat protein in
      solution was determined by two- and three-dimensional nuclear magnetic resonance
      methods and molecular dynamics calculations. The protein structure exhibits a
      well-defined hydrophobic core of 15 amino acids that serves as a scaffold for two
      flexible domains corresponding to the NH2- and COOH-terminal regions. The core
      region is a strictly conserved sequence region among the known Tat proteins. The
      structural data can be used to explain several of the observed features of Tat
      proteins.

PMID- 7515508
TI  - [Animal models of bronchial hyperreactivity].
AB  - Airway responsiveness is increased in a variety of airway diseases. To understand
      the mechanism of enhanced airway responsiveness, in particular as it pertains to
      asthma, animal models have been developed and extensively explored. The guinea
      pig and Basenji-greyhound dog are the best characterized animals showing airways
      hyperresponsiveness and appear to bear substantial resemblances to asthmatic
      human subjects. Challenge with bronchoconstrictive agonist results in
      bronchoconstriction and transient vascular leak. Both phenomena contribute to the
      degree of airway narrowing. Adenosine challenge tests not only the responsiveness
      of the airways, but also that of the airway effector cells such as the mastocyte.
      Bradykinin and tachykinin cause indirect airway narrowing, probably by liberation
      of leukotrienes. Responsiveness can be enhanced by immune and non-immune
      challenges. Ozone, Sephadex, various contractile agonists (leukotriene D-4,
      bradykinin, platelet-activating factor), as well as certain cytokines (IL-1, IL
      2, TNF-alpha) can enhance airway responsiveness. Cyclooxygenase and lipooxygenase
      products appear to be involved. Allergen-induced hyperresponsiveness is
      associated with airway inflammation and appears to involve bradykinin and PAF
      acutely and growth of airway smooth muscle chronically.

PMID- 7515514
TI  - The dose-related effect of intradiscal chymopapain on rabbit intervertebral
      discs.
AB  - STUDY DESIGN: This study analyzed the histological and biochemical responses of
      intervertebral disc tissue to intradiscal injection of varying amounts of
      chymopapain. OBJECTIVE: To determine the appropriate amount of chymopapain needed
      to accomplish effective degradation of proteoglycans (PG) in the nucleus pulposus
      of intervertebral discs. SUMMARY OF BACKGROUND DATA: Chymopapain is an accepted
      treatment alternative for patients with disc herniations. The recommended
      clinical dose of 2,000-4,000 pKats per injection is derived from early animal
      studies and empirical results in man. A lower effective dose could reduce the
      complication rate while providing similar clinical results. METHODS: Twenty to
      4,000 pKat of chymopapain was injected into rabbit discs, and the level of
      keratan sulfate (KS) epitope in serum was measured at different times after the
      injection. The animals were killed after 6 days and the injected and two
      neighboring discs were examined histologically. RESULTS: The serum KS level did
      not change appreciably after injection of 20 pKat, rose moderately at 100 and 200
      pKat, and rose strongly at 500 pKat. Doses greater than 500 pKat did not result
      in further increase in the KS level. CONCLUSION: Degradation of the disc
      proteoglycans is dose dependent and reaches a maximum at 500 pKat. Higher doses
      appear not to cause further loss of aggrecan molecules, and injection of more
      than 1,000 pKat produces significant annular destruction.

PMID- 7515515
TI  - Reversal of bleomycin lung toxicity with corticosteroids.

PMID- 7515513
TI  - High-intensity chemotherapy with peripheral blood progenitor cell support.
AB  - In a series of clinical studies at Memorial Sloan-Kettering Cancer Center, we
      have used hematopoietic growth factors and peripheral blood-derived hematopoietic
      progenitor cells to facilitate delivery of multiple courses of high-dose
      chemotherapy at abbreviated treatment intervals. In these studies, we have
      demonstrated the feasibility of cross-over regimens involving induction
      chemotherapy with high-dose cyclophosphamide, supported by granulocyte colony
      stimulating factor and followed by multiple peripheral blood leukapheresis to
      harvest progenitor cells. These cells are then used as rescue for the
      consolidation component of treatment, which, in the earlier-generation studies,
      consisted of a single course of high-dose carboplatin/etoposide/cyclophosphamide
      chemotherapy. In subsequent studies, patients received either four courses of
      high-dose carboplatin or carboplatin/cyclophosphamide or tandem courses of
      thiotepa. In all cases, the planned interval between treatments was 14 days, and
      the achieved median was approximately 16 days. These studies show that the
      administration of high-intensity regimens that deliver multiple courses of very
      high-dose chemotherapy at relatively brief intervals is feasible. Our current
      research focuses on exploiting these findings to devise disease-specific regimens
      for breast and ovarian cancer.

PMID- 7515516
TI  - Exposure of bus and taxi drivers to urban air pollutants as measured by DNA and
      protein adducts.
AB  - Urinary 1-hydroxypyrene, lymphocyte DNA adducts, serum protein-bound PAH and
      hemoglobin-bound alkene adducts were analysed from 4 groups of non-smoking men:
      urban and suburban bus drivers, taxi drivers and suburban controls. The only
      differences between the groups were in DNA adducts between suburban bus drivers
      and controls, and in DNA adduct and plasma protein PAH-adducts between taxi
      drivers and controls.

PMID- 7515517
TI  - Assessment of occupational exposure to diesel exhaust. The use of an immunoassay
      for the determination of urinary metabolites of nitroarenes and polycyclic
      aromatic hydrocarbons.
AB  - In a repair shop for train engines a pilot study was conducted to investigate
      occupational exposure to diesel exhaust. 1-Nitropyrene was determined in
      stationary sampled total suspended particulate matter collected on 2 consecutive
      workdays. Air concentrations of particulate associated 1-nitropyrene varied from
      non-detectable to 5.6 ng/m3. In spot urine samples collected on Sunday, Monday
      and Tuesday urinary metabolites of polycyclic aromatic hydrocarbons and their
      nitro-substituted derivatives were determined using an immunoassay. In the urine
      samples of 3 diesel mechanics both cumulative and average excretion of urinary
      metabolites over 48 and 72 h were significantly enhanced (P < 0.05) as compared
      to the excreted levels in urine samples from 2 office clerks.

PMID- 7515518
TI  - Comparison of biological effects of different polycyclic aromatic hydrocarbons in
      lung cells of hamster and rat in vitro.
AB  - The cytotoxicity and frequencies of transformation induced by 5 environmental
      polycyclic aromatic hydrocarbons (PAH) in hamster (M3E3/C3) and rat (WRB K3) lung
      cells were compared. Both cell strains investigated here retain major metabolic
      characteristics of the target cells in vivo and are thus able to effectively
      metabolize, i.e. activate, PAH. Cytotoxic effects of the carcinogen were
      determined in colony-forming assays and the PAH tested induced dose-dependent
      cytotoxic responses in the M3E3/C3 and WRB cells. They could then be classified
      into strong and weak cytotoxicity. Compared to the hamster cell system, the WRB
      cells were generally shown to be more sensitive. The transforming capacity of the
      compounds was determined by a soft agar colony formation assay detecting cells
      with anchorage independency (AI). All PAH investigated induced transformation to
      AI growth in both cell systems. The transforming activity of the PAH, relative to
      benzo[a]pyrene (B[a]P) as a reference substance, was determined to facilitate
      their ranking. This order of transforming potency appears to be similar to that
      observed in animal studies.

PMID- 7515521
TI  - Priming of HIV replication by tRNA(Lys3): role of reverse transcriptase.
AB  - The fundamental role played by reverse transcriptase in the replication of
      retroviruses has stimulated the study of the mechanism of action of this enzyme.
      The reverse transcriptase of the type 1 human immunodeficiency virus forms a
      stable complex with its cognate transfer RNA replication primer (tRNA(Lys3)).
      Here, we outline the role of this enzyme in the selection of its primer tRNA, the
      annealing of primer tRNA to the complementary region of the retroviral genome,
      and the first attempts to use the reverse-transcriptase-tRNA complex as a new
      target for antiviral agents.

PMID- 7515520
TI  - Recent biologic studies on suicide.
AB  - This paper selectively reviews the author's recent studies on suicidal behavior
      in depression. Data are reviewed from a study of depressed patients who had
      monoamine metabolites measured in both the cerebrospinal fluid (CSF) and urine.
      Depressed patients who had attempted suicide had significantly reduced CSF
      concentrations of the dopamine metabolite homovanillic acid (HVA) and
      significantly lower urinary outputs of HVA than patients who had not attempted
      suicide. Similarly, patients who went on to reattempt suicide over a 5-year
      follow-up period had both significantly reduced CSF concentrations of HVA and
      lower urinary outputs of HVA than patients who did not reattempt. These data
      suggest a role for diminished central dopaminergic neurotransmission in suicidal
      behavior in depression. Patients who had made a violent suicide attempt also
      showed evidence of dysregulation of the hypothalamic-pituitary-adrenal axis.

PMID- 7515519
TI  - CSF 5-HIAA predicts suicide risk after attempted suicide.
AB  - Suicide risk after attempted suicide, as predicted by cerebrospinal fluid (CSF)
      monoamine metabolite concentrations, was studied in a sample of 92 psychiatric
      mood disorder inpatients admitted shortly after attempting suicide. The potential
      of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the CSF to
      predict suicide risk within the first year after attempted suicide was studied by
      means of survival analysis after after median split subgrouping. Eleven patients
      (12%) committed suicide within 1 year after attempted suicide. Eight of these
      belonged to the below-the-median (< 87 nM) CSF 5-HIAA subgroup, that is, the
      suicide risk was 17% as compared with 7% among those with above-the-median CSF 5
      HIAA. The cumulative number of survived patient-months during the first year
      after attempted suicide was significantly lower in the low CSF 5-HIAA subgroup.
      It was concluded that low CSF 5-HIAA predicts short-range suicide risk after
      attempted suicide in mood disorder psychiatric inpatients. These findings lend
      further support to the serotonin hypothesis of suicide risk.

PMID- 7515523
TI  - Genuine genetics or conceited convenience?

PMID- 7515522
TI  - Cortical columns as devices for maximizing neuronal diversity.
AB  - Columns are a fundamental feature of cerebral cortex organization, yet the
      function served by this architecture remains elusive. Here it is proposed that
      the columnar organization of the cortex serves to maximize diversity of neuronal
      connections in supragranular cortical layers.

PMID- 7515524
TI  - Histochemical localization of nitric oxide synthase in the CNS.

PMID- 7515525
TI  - Pathogenesis of Huntington's disease.

PMID- 7515527
TI  - Spontaneous Ca2+ spikes and waves in embryonic neurons: signaling systems for
      differentiation.
AB  - Many excitable cells are specialized to promote Ca2+ influx at early stages of
      development. This article focuses on spontaneous fluctuations of intracellular
      Ca2+ that are observed during this period. Removal of Ca2+ or suppression of
      influx alters subsequent differentiation. Thus these signals appear to regulate
      aspects of early maturation.

PMID- 7515528
TI  - Temporal and spatial properties of local circuits in neocortex.
AB  - A large body of anatomical data has detailed many complexities of neocortical
      circuitry, and physiological studies have indicated some roles for this circuitry
      in the complex functions of the cortex. Until recently, however, we have little
      precise information about the spatio-temporal properties of synaptic connections
      between individual neocortical neurones. Studies of synaptic responses elicited
      in one neocortical neurone by action potentials in another, and parallel
      morphological studies that have identified these neurones and the synaptic
      connections between them, have now described these parameters for certain types
      of local circuit connection in the neocortex. Some of these studies confirmed
      previous observations and inferences, but others provided major surprises.
      Evidence indicates that the class of both the presynaptic and postsynaptic
      neurone together determine a wide range of synaptic properties, such as the type
      of postsynaptic receptors involved and the temporal pattern of transmitter
      release, so that each type of synapse displays unique properties. A role for
      retrograde diffusable messages in determining the temporal properties of these
      circuits is postulated.

PMID- 7515526
TI  - Functional mapping of verbal memory and language.
AB  - Francis O. Schmitt wrote in his introduction to The Mindful Brain that 'Many
      theories of higher brain function (learning, memory, perception, self-awareness,
      consciousness) have been proposed; but in general these lack cogency with respect
      to the established anatomical and physiological facts and are without biophysical
      and biochemical plausibility'. A central aim of functional mapping studies of the
      human brain is a physiological and anatomical description of the brain regions
      that participate in different brain functions. Language and memory have become,
      with the advent of modern imaging technologies, the subject of a comparatively
      large number of mapping studies in recent years. The quality of the data and of
      the experimental design continue to evolve so that sophisticated questions are
      being addressed, and convergent findings are now being reported. This article
      will critically review mapping studies of language and memory and assess how they
      advance our knowledge of the functional organization of these human faculties.

PMID- 7515531
TI  - Spatial dynamics of second messengers: IP3 and cAMP as long-range and associative
      messengers.
AB  - Recent imaging experiments have revealed the distinct spatial dynamics of second
      messenger actions. In general, actions of Ca2+ tend to be local, whereas those of
      other messengers such as inositol 1,4,5-trisphosphate (IP3) and cAMP are long
      range. In pancreatic acinar cells, IP3 generated at the base can diffuse across
      the cell and evoke a spatially confined Ca2+ signal in the apical pole,
      triggering enzyme and fluid secretion. Similar mechanisms might also operate in
      other cell types. We propose that the distinct dynamics of messengers might be
      relevant to neuronal function: IP3 and cAMP could convey signals over long
      distances along neurites, and serve as mediators for association and co
      operation, for example, during learning.

PMID- 7515529
TI  - System-wide repercussions of damage to the immature visual cortex.
AB  - Damage of the primary visual cortex in mammals, including humans, severely
      disrupts vision by disconnecting much of the cognitive-processing machinery of
      extrastriate cortex from its source of visual signals in the retina. Studies of
      the anatomical consequences of damage to the immature primary visual cortex in
      cats reveal system-wide repercussions on neural circuitry that includes the
      retina, thalamus, midbrain and extrastriate cortex. The repercussions modify
      circuits that support relatively normal signal processing and the sparing of
      certain visually guided behaviors such as aspects of complex-pattern recognition
      and orienting to novel stimuli introduced into the visual field. These studies
      have implications for understanding the consequences of damage to the visual
      cortex in infant monkeys and humans, and for devising therapeutic strategies to
      attenuate defects in vision induced by cortical lesions.

PMID- 7515530
TI  - An opiate-receptor gene family reunion.

PMID- 7515532
TI  - [Value of bilio-digestive anastomosis in the treatment of pancreatic head
      cancer].

PMID- 7515533
TI  - Light microscopical immunohistochemical study on parathyroid adenoma in primary
      hyperparathyroidism.
AB  - Fifteen adenomatous parathyroid glands obtained from 15 patients with primary
      hyperparathyroidism were examined both pathologically and immunohistochemically
      and connected with the clinical data for each patient. Four consecutive sections
      of the largest section surface of each resected adenomatous parathyroid gland
      were utilized for 4 kinds of stains, that is, hematoxylin-eosin, Grimelius and
      the immunohistochemical stains for parathyroid hormone (PTH) and chromogranin A.
      The results were as follows: (1) The large adenomatous parathyroid glands showed
      strong reactions to PTH as well as chromogranin A and Grimelius. On the other
      hand, the parathyroid adenoma obtained from a 9-year-old boy with hypercalcemic
      crisis showed almost no stain-positive cells for both PTH and chromogranin A. It
      is assumed that the former phenomenon reflects a substantial storage of secretory
      granules, while the latter reflects exhaustion of these granules. (2) The normal
      parathyroid cells in the neoplastic parathyroid glands generally showed stronger
      reactions to PTH and chromogranin A than neoplastic parathyroid cells. This
      suggests that normal cells in the neoplastic parathyroid glands may have their
      release of PTH rather than its synthesis suppressed, and also might support the
      hypothesis of some authors that chromogranin A or SP-I might contribute to
      stabilization of PTH or the secretory vesicle.

PMID- 7515534
TI  - Prognostic value of urokinase plasminogen activator for prostatic carcinoma.
AB  - The usefulness of routine clinical application of the urokinase plasminogen
      activator in prostate cancer was evaluated. The urokinase values of prostate
      cancer confined to the organ, with extraprostatic spread and with metastatic
      disease did not differ and showed no significant difference in comparison with
      benign prostatic hyperplasia. Urokinase is not a useful parameter in clinical
      routine.

PMID- 7515536
TI  - Immunohistochemical staining of feline malignant fibrous histiocytomas.
AB  - Malignant fibrous histiocytoma was diagnosed in seven cats from biopsy specimens
      received at the University of Missouri Veterinary Medical Diagnostic Laboratory
      during a 4-year period from 1987-1991. Tissue blocks from formalin-fixed
      specimens were resectioned and stained for type I (AE1) and type II (AE3)
      cytokeratins, desmin, S100 protein, vimentin, and alpha 1-antitrypsin by the
      avidin biotin peroxidase complex method with diaminobenzidine (DAB) chromogen.
      None of the tumors stained positively for alpha 1-antitrypsin. Four of seven of
      the tumors had similar immunohistochemical staining results, with positive
      staining for type I and type II cytokeratins, desmin, S100 protein, and vimentin.
      Of the remaining three, one stained positively only for S100 protein and
      vimentin; one stained positively for vimentin only; and one was negative for all
      six antigens. Based only on immunohistochemical staining results, three of the
      tumors could possibly be reclassified: one as a melanoma, one as a probable
      fibrosarcoma, and one as unknown. These results also indicate that feline
      malignant fibrous histiocytomas show a diversity of intermediate filament
      expression, as do human tumors. Our results also do not support the theory that
      malignant fibrous histiocytomas are of histiocytic origin.

PMID- 7515535
TI  - [The mechanism of the action of local transrectal hyperthermia in treating
      prostatic adenoma].
AB  - Local transrectal hyperthermia (LTH) was used to treat 139 patients with
      prostatic adenoma aged 54-86 if they did not demand urgent surgery. LTH mechanism
      of action was studied by blood rheology, immunity characteristics, prostatic
      tissue gentamycin concentrations, morphological alterations after hyperthermia
      followed by TUR and adenomectomy. Clinical evaluation covered dysuria dynamics,
      uroflowmetry values, quantitation of residual urine and measurement of the
      prostate. The patients combined adenoma with chronic prostatitis, acute urine
      retention, cystostomy fistula (43, 22 and 16 patients, respectively). A microwave
      electromagnetic hyperthermia unit "Yakhta-4M" made in Russia (434 MHz, 200 W)
      heated the prostate to 43-44 degrees C. Two procedures a week of 60 min duration
      were performed within 3-5 weeks. LTH results in reduced blood viscosity, has no
      effect on blood coagulation, enhances neutrophil phagocytic function inhibiting
      their metabolic activity without affecting humoral immunity, raises 2-fold
      gentamycin concentrations in the prostatic tissue compared to blood and urine
      levels. Histologically, LTH does not alter prostatic parenchyma, but induces
      structural shifts in the muscular and connective tissue of the stroma producing
      stabilizing action on acinar epithelium. Clinical picture was characterized by
      subjective improvement in 72% of those treated, by urination recovery in 70% of
      the patients. 73% of the latter experienced cystostomy drainage which rid them of
      the fistula without operation. In general, mechanism of LTH action is brought to
      improvement of microcirculation, enhancement of cellular phagocytosis with a
      tendency to prostatic tissue sclerosing and stabilization of growth of the
      glandular tissue.

PMID- 7515537
TI  - Inhibitory effects of recombinant feline interferon on the replication of feline
      enteropathogenic viruses in vitro.
AB  - Antiviral activities of a recombinant feline interferon (rFeIFN) KT-80 were
      evaluated against feline enteropathogenic viruses in feline and canine cell
      lines. Sensitivity to antiviral activities of the rFeIFN varied with cell types;
      Felis catus whole fetus (fcwf-4) cells were more sensitive than Crandell feline
      kidney cells, but no sensitivity was found for Madin-Darby canine kidney cells
      when vesicular stomatitis virus was used as a challenge virus. Reductions were
      generally IFN dose-dependent and were more consistent when the cells were
      continuously treated with the rFeIFN than when they were pretreated only before
      viral challenge. Compared with each virus control culture of fcwf-4 cells, yields
      of rotavirus, feline panleukopenia virus (FPLV), feline calicivirus and feline
      infectious peritonitis coronavirus were reduced by ranges of 1.3 to < or = 3.1
      log10, 0.6 to 1.6 log2, 0.8 to 3.7 log10 and 0.5 to 0.6 log10, respectively, in
      the cultures continuously treated with 10 to 10000 U of the rFeIFN. The yield
      reduction of FPLV was considered to be in part attributable to inhibition of cell
      growth by the rFeIFN supplemented in the medium.

PMID- 7515539
TI  - Improvisation in wrap-around toe-to-thumb transfer.
AB  - Wrap-around partial great toe transfer, a one time dream, is now a well
      established and universally accepted method of thumb reconstruction. In this
      technique, part of the soft tissue of the great toe are wrapped around and shaped
      to the size of the graft from iliac bone in such a manner that a thumb of normal
      dimensions and shape is produced. Instead of the iliac bone graft, we found great
      merit in using the second metacarpal from the traumatised hand to be
      reconstructed. In this paper its use and merits are elaborated.

PMID- 7515538
TI  - Multipurpose vectors designed for the fast generation of N- or C-terminal epitope
      tagged proteins.
AB  - In this paper are described a set of new high-copy-number yeast vectors, which
      are specially designed for the conditional expression of epitope-tagged proteins
      in vivo. One of the major advantages of these plasmids is that they allow
      polymerase chain reaction-amplified open reading frames to be automatically fused
      in frame with the epitope-coding sequence, avoiding longer procedures such as
      site-directed mutagenesis. This heterologous construction can be realized either
      at the 5'-end of the coding sequence, in the pYeF1 vector, or at its 3'-end, in
      pYeF2, generating N- or C-terminal tagged proteins, respectively. Moreover, to
      increase the usefulness of the method, derivatives of the two basic URA3-borne
      pYeF1 and pYeF2 were constructed, carrying either the HIS3 or TRP1 gene as a
      marker of selection. These vectors could be of use for the purpose of functional
      analysis of the newly discovered genes resulting from the systematic sequencing
      of the yeast genome. Here, we present results showing the functional expression
      and the efficient immunoprecipitation of the epitope-tagged Rna15 protein, which
      is involved in Saccharomyces cerevisiae mRNA stability.

PMID- 7515541
TI  - Reconstruction of a devastating electric injury: case-report.
AB  - In the submitted case-report the authors describe a combination of a
      reconstruction operation with an orthopaedic approach to a devastating injury of
      the shoulder and elbow in a 26-year-old patient after an electric current injury.
      The total extent of the skin damage was 13% T.B.S.A. with localization on the
      right side of the chest, right arm, left elbow and shoulder. After fascial
      excisions the proximal part of the humerus was amputated with fixation by means
      of cerclage to the scapula. This defect was covered with the musculus latissimus
      dorsi flap and the defect on the elbow was covered by a tube pedicle flap.

PMID- 7515540
TI  - Sequelae of an injury from the Second World War treated by free flap transfer.
AB  - The authors present the case-history of patients with chronic osteomyelitis of
      the proximal third of the tibia-resulting from an injury during the Second World
      War. The defect of bone and soft tissues was treated by free transfer of a
      musculocutaneous flap. The behaviour of the flap in the osteomyelitic cavity is
      followed up and checked by repeated CT and NMR examinations.

PMID- 7515542
TI  - Reconstruction of penis by prefabrication on forearm.
AB  - Posttraumatic total loss of penis in a 20 years old patient was reconstructed by
      prefabrication of the organ on the forearm using distally based radial forearm
      flap before transferring it to the perineum using extracorporeal method of tissue
      transfer. In this case report merits of the technique and the concept are
      discussed.

PMID- 7515543
TI  - Reconstruction of the lower eyelid after excision of major tumours.
AB  - The authors report on a pretentious surgical procedure which is essential after
      excision of major tumours of the lower eyelid. They describe in detail the
      reconstruction of the lower lid in case of a 70% loss of the lid. They used
      Mustard's method during which the tarsoconjunctival defect was replaced by a
      mucochondral implant from the nasal septum. After suture of the implant the
      residual skin defect was covered by rotation of a cheek flap. A two-stage
      reconstruction of the lower lid was used in case of 95% excision of the width of
      the lid. In the first stage the authors transferred a tarsoconjunctival flap from
      the upper lid and covered the musculocutaneous part by a transplant of
      retroauricular skin. In the second stage they released the tarsoconjunctival flap
      with subsequent plastic surgery of the lower lid. In 100% loss of eyelid the
      authors used for replacement of the tarsus of the lower lid a mucochondral
      implant from the nasal septum and to cover the skin defect they used a bridge
      shaped myocutaneous flap from the upper lid in the defect of the-lower lid.

PMID- 7515544
TI  - Reduction mammaplasty at the Department of Plastic surgery in Prague.
AB  - The authors present a review of the history of surgery of hypertrophic breast at
      the Department of Plastic Surgery in Prague. The period from 1928 to the present
      time was divided into stages by the dominating surgical technique. The authors
      emphasize the importance of careful selection of the surgical procedure with
      regard to the type and grade of the defect.

PMID- 7515545
TI  - Tooth eruption in patients with cleft lip and palate.
AB  - In boys with a total unilateral cleft the course of eruption of deciduous and
      permanent teeth in the quadrant of the maxilla with the cleft was investigated
      and compared with the intact quadrant of the maxilla. The greatest retardation
      (two years) during eruption was found in deciduous and permanent second incisors
      in the maxillary quadrant affected by the cleft. This retardation is according to
      the authors associated with gross morphological changes such as duplication of
      the second incisor and its altered shape. The second upper permanent incisor
      erupts only in 60% of the patients and this can be explained by frequent
      hypodontia. Retarded eruption was observed also in the maxillary quadrant with
      the cleft in the permanent canine (one year), the first (one and a half year) and
      second permanent premolar (six months). In these teeth the crowns are not
      perceptibly malformed and the delayed eruption may be associated with lack of
      space in the hypoplastic quadrant of the maxilla on the side of the cleft. The
      permanent first incisor and permanent first and second molar erupt symmetrically
      in both maxillary quadrants.

PMID- 7515546
TI  - The use of bone grafts in orofacial clefts.
AB  - In the repair of orofacial clefts can be used various techniques of bone
      transplantations. The authors describe the long term experience with untoward
      effects of primary bone grafts on the growth of the maxilla. They discuss the
      effects of a secondary bone graft consisting of a compact bone. This bone graft,
      however, does not eliminate the defect of the alveolar process. They prefer the
      technique of an autotransplantation of spongious bone grafts applied after the
      onset of puberty. This graft reconstructs he threshold of the nostril and the
      alveolar process. It exerted favorable effects on the development of the alveolar
      process and of the anterior segment of the maxilla.

PMID- 7515547
TI  - Effects of soft tissue and osseous bridge on facial configuration in adults with
      unilateral cleft lip and palate.
AB  - Roentgencephalometric study was used for the assessment of 16 adult males with
      unilateral cleft lip and palate and an osseous bridge and of 10 males with a soft
      tissue bridge. They were compared with 32 individuals with a complete cleft and
      with a control group of 50 normal males. All patients were operated upon and
      subsequently treated with the same methods. In contrast to the soft bridge, an
      osseous bridge prevents the reduction of upper face height, and an increased
      width of the nasal cavity. Both an osseous and a soft tissue bridge exert a
      favorable effect on the shortening and retrusion of the maxilla and thus also on
      the maxillo-mandibular relations and on facial configuration. The thickness of
      the upper lip is related to the presence of a soft bridge, while deviations of
      the lower jaw and the posterior position of the maxilla are not related to the
      presence of either type of bridge. Alveolar retroinclination was insignificantly
      smaller in the presence of both types of bridges. These differences disclosed
      that clefts with soft bridges cannot be pooled with complete clefts (or with
      clefts with osseous bridges), when there is not definite evidence of the same
      proportion of both forms of clefts in the series used for comparison.

PMID- 7515548
TI  - Facial asymmetry: type, extent and range of normal values.
AB  - For analysis of facial asymmetry (signed, absolute, relative) a group of 720
      normal children aged 6-18 years was examined. Twelve direct dimensions measured
      on both sides of the face were assessed. The results revealed that the extent of
      facial asymmetry is the same in both sexes and does not change with age. Facial
      asymmetries have mostly a fluctuating character, usually with slight predominance
      of the right side. With the help of double standard deviations of signed
      asymmetry, the range of normal asymmetry for lateral facial dimensions was
      determined as 4-5 mm. The definition of the borderlines or normal and abnormal
      asymmetries may be of practical value in some medical disciplines.

PMID- 7515549
TI  - Integrin expression in middle ear cholesteatoma.
AB  - Cholesteatoma is lined by a squamous keratinizing epithelium exhibiting most of
      the features of normal epidermis. In this study, we investigated by
      immunohistochemistry the expression of integrin adhesion molecules in primary
      acquired and recurrent cholesteatomas, and compared it with common epidermal
      cysts and normal human skin. The results showed that cholesteatoma epithelium
      exhibited a markedly augmented expression of alpha v integrin subunit and a
      corresponding increased deposition of vitronectin (alpha v ligand) in the
      surrounding stroma as compared to epidermal cyst and normal human skin. In
      contrast, the expression pattern of alpha 2 beta 1, alpha 3 beta 1, and alpha 6
      beta 4 integrins as well as the distribution of laminin, collagen IV and
      fibronectin were similar in cholesteatomas, epidermal cysts and normal human
      skin. Similar staining pattern was observed in primary acquired and recurrent
      cholesteatoma.

PMID- 7515550
TI  - Localisation of secretory leucocyte proteinase inhibitor mRNA in nasal mucosa.
AB  - Human secretory leucocyte proteinase inhibitor (SLPI) is a low-molecular weight,
      acid-stable inhibitor of polymorph-nuclear granulocyte elastase and cathepsin G.
      Previous reports have demonstrated the existence of SLPI in the respiratory
      tract, salivary glands and cervical mucosa. Positive staining for SLPI using
      immunohistochemical techniques has been reported in serous glands in nasal
      mucosa. We now confirm this observation and show, using in situ hybridization,
      that the pattern of expression of mRNA corresponds to the distribution of the
      encoded protein, SLPI. This, together with the high concentration of SLPI in
      nasal secretions, confirms the hypothesis of a local production of SLPI in the
      mucous membranes.

PMID- 7515551
TI  - Squamous cell carcinoma of the respiratory tract following laryngeal
      papillomatosis.
AB  - With the object to disclose an association between laryngeal papillomatosis and
      laryngeal carcinoma, we reviewed 102 patients with laryngeal papillomatosis
      treated between 1950 and 1979. Seven cases of laryngeal carcinomas were recorded
      and 1 patient with spread of papilloma to the bronchial tree developed a
      bronchial carcinoma. The time between onset of papilloma and diagnosis of
      carcinoma was 4-55 years (mean 24 years). For laryngeal carcinoma the ratio of
      observed to expected cases was 88. Of the 8 patients developing respiratory tract
      carcinoma, 2 had received treatment with radiation and 2 had been treated with
      Bleomycin. Four of these 8 patients were known smokers. This study shows that
      papillomatosis is more often associated with laryngeal carcinoma than previously
      reported. It appears, however, that laryngeal papillomas alone seldom induce
      carcinomas. Apart from irradiation and smoking, Bleomycin could be an important
      co-factor.

PMID- 7515552
TI  - Diagnosis and treatment for Bell's palsy associated with diabetes mellitus.
AB  - The method of detecting diabetes mellitus and estimating the diabetic control
      status in patients with Bell's palsy, and the effect of high-dose steroid therapy
      for Bell's palsy accompanied by diabetes were investigated. From October 1987,
      hemoglobin A1c (HbA1c) was introduced to detect diabetes in 288 out of 372
      patients with Bell's palsy, as a screening test for DM. Thirty-six diabetics with
      complete facial palsy were treated by high dose steroid therapy as described by
      Stennert. Hemoglobin A1c was useful in diagnosing diabetes and in assessing the
      diabetic control. Many patients under diabetic therapy kept their diabetes under
      good control. In cases of complete palsy, high-dose steroid therapy, at a cure
      rate of 97.4%, was highly effective in treating diabetes-accompanied Bell's
      palsy.

PMID- 7515553
TI  - Factors affecting the efficiency of peripheral blood stem cell collection in
      children treated with chemotherapy and G-CSF.
AB  - This retrospective study attempts to clarify the optimal timing for peripheral
      blood stem cell (PBSC) collection after conventional chemotherapy followed by
      granulocyte-colony stimulating factor (G-CSF) administration. Leukapheresis was
      performed 32 times in nine children with various cancers during bone marrow
      recovery phase following transient pancytopenia after chemotherapy. (On two
      occasions, leukapheresis was excluded because many leukemic blasts were
      included). When the number of white blood cells (WBC) exceeded 1.8 x 10(10)/L
      after administration of G-CSF (200 micrograms/m2, continuous infusion), many more
      CD34+ cells were contained in the collected peripheral mononuclear cells (P >
      0.02) and a sufficient number of PBSC for transplantation (> or = 10 x 10(8)
      CD34+ cells/kg) was obtained after one run in 15 of 17 leukapheresis sessions. In
      contrast, sufficient PBSC were obtained only in one of 13 runs of leukapheresis
      when the number of WBC was < 1.8 x 10(10)/L. The number of WBC on the day when
      PBSC were collected correlated with collected nuclear cell number (r = 0.60), but
      not with the CD34+ cell ratio. The ratio was higher only when both platelets and
      reticulocytes increased in parallel with WBC. We conclude that sufficient PBSC
      collection is possible after conventional chemotherapy using G-CSF, when
      hematopoietic recovery is parallel, without the use of high-dose chemotherapy.

PMID- 7515554
TI  - Trypanosoma cruzi: studies on the reactivity of antibodies bound to the surface
      of blood forms at the early phase of infection.
AB  - The specificity and reactivity of antibodies bound to the surface of Trypanosoma
      cruzi blood forms at the very early acute phase of murine infection was
      investigated. Surface-bound antibodies of the IgG and IgM isotypes were recovered
      from blood forms upon incubation at 37 degrees C. The eluted antibodies
      immunoprecipitated several trypomastigote surface polypeptides from 80 to 100
      kDa. In contrast, for epimastigotes a very faint reactivity was detected only for
      antigens of 50 and 95 kDa. The shed antibodies promoted in vitro complement
      mediated lysis of live blood forms and reacted with fixed trypomastigotes by
      immunofluorescence. Thus, blood forms are already coated with active
      trypomastigote-specific antibodies with a potential role in the host defense,
      although the low levels of serum antibodies have prevented the demonstration of
      humoral protection at the early stages of infection.

PMID- 7515555
TI  - New use for alpha blockers: benign prostatic hyperplasia.
AB  - Treatment with alpha 1-adrenergic blockers can be a reasonable alternative to
      surgery for patients with symptomatic benign prostatic hypertrophy. Alpha
      blockers may also be useful as an adjunct to finasteride in the treatment of this
      disorder. Pretreatment evaluation is essential to ensure that the patient does
      not have an infection, prostate cancer or another serious cause of the prostatic
      symptoms. The patient should be monitored for side effects, and the dosage should
      be increased slowly. Side effects can be minimized by administering the
      medication at night and reversed by discontinuing the drug. In more than 50
      percent of patients, treatment with alpha blockers results in objective and
      subjective symptomatic relief.

PMID- 7515556
TI  - Low-protein diet regulates a proximal nephron insulin-like growth factor binding
      protein.
AB  - Previous studies have demonstrated that the glomerulus and proximal tubule
      basolateral membrane possess both insulin-like growth factor (IGF) receptors and
      IGF-binding proteins (IGFBPs). The purpose of this study is to examine the
      control of these proteins in defined nephron segments during dietary protein
      restriction. Animals were fed isocaloric 6% (low-protein [LP]) or 40% (high
      protein) protein diets for 7 to 10 days. 125I[IGF] affinity labeling of membranes
      prepared from isolated glomeruli or proximal tubule basolateral membranes
      demonstrated two proteins on autoradiograms of 6% polyacrylamide gels with
      molecular weights of 140,000 d and more than 200,000 d that were blocked by 300
      nmol/L unlabeled IGF-I. The lower molecular weight species has been identified
      previously as the alpha subunit of the IGF-I receptor and was upregulated by a 6%
      LP diet. The upregulation of the IGF-I receptor was evident on 12% polyacrylamide
      gels of both glomeruli and basolateral membranes. Another protein with a
      molecular weight of approximately 38,000 d also was upregulated by LP diet. The
      protein was evident on 125I-IGF-I ligand blots and was immunostained with IGFBP-5
      antibodies. Cytosol prepared from cortical tissue also demonstrated a 31,000-d
      protein that was immunostained with IGFBP-5 antibodies in animals fed a LP diet,
      but not in animals fed a high-protein or normal diet. RNA prepared from cortical
      tissue and hybridized with a IGFBP-5 cDNA probe revealed a 6.0-Kb transcript that
      was increase by LP diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515558
TI  - Correlation of intratumoral endothelial cell proliferation with microvessel
      density (tumor angiogenesis) and tumor cell proliferation in breast carcinoma.
AB  - Tumor angiogenesis is essential for tumor growth and metastasis, and intratumoral
      microvessel density correlates with prognosis in breast carcinoma. Yet, how
      intratumoral microvessel density correlates with tumor cell and intratumoral
      endothelial cell proliferation remains incompletely understood. To this end, we
      stained 57 formalin-fixed, paraffin-embedded breast carcinomas with antibody MIB1
      to determine tumor cell Ki67 labeling index and with anti-CD34 to observe
      microvessels. We correlated the tumor cell Ki67 labeling index and mitotic figure
      index with intratumoral microvessel density. Using a double labeling technique
      combining antibody MIB1 and anti-CD34, we measured intratumoral endothelial cell
      proliferation in 20 of these cases and correlated these findings with tumor cell
      Ki67 labeling index, mitotic figure index, and intratumoral microvessel density.
      The intratumoral Ki67-labeling index was 45-fold greater (P < 0.000001) than that
      of microvessels in adjacent benign breast. Yet, endothelial cell Ki67 labeling
      index did not correlate with intratumoral microvessel density, tumor cell Ki67
      labeling index, or mitotic figure index nor did intratumoral microvessel density
      correlate with tumor cell Ki67 labeling index or mitotic figure index. These
      findings suggest that, although endothelial cells are actively proliferating
      within the tumor, intratumoral microvessel density and intratumoral endothelial
      cell proliferation are independent of each other and of tumor cell proliferation.
      Thus, intratumoral microvessel density, endothelial cell proliferation, and tumor
      cell proliferation may be regulated by separate mechanisms.

PMID- 7515559
TI  - Differential expression of estrogen, progesterone, and epidermal growth factor
      receptors in normal, benign, and malignant human breast tissues using dual
      staining immunohistochemistry.
AB  - Distribution of estrogen (ER), progesterone (PR) receptors, and epidermal growth
      factor (EGF) receptors was assayed by dual staining immunohistochemistry on 28
      selected cytosolic ER-positive breast carcinomas and 22 nonmalignant breast
      tissues. ER-positive tumor cells were detected in 26 (93%) and EGF receptor
      positive tumor cells were detected in 7 (25%) carcinomas. In five tumors both ER
      and EGF receptors were detected but localized in distinct tumor cells. Only in
      one case of ductal carcinoma in situ co-expression was observed in a subset of
      tumor cells. In contrast, simultaneous expression of ER/PR and EGF receptors was
      observed in non-neoplastic ductal remnants in the majority of the carcinomas and
      the fibroadenomas. In addition, double-positive cells were occasionally detected
      in luminal epithelial cells of normal breast tissue and mastopathies. This study
      shows that ER/PR and EGF receptors in breast tumor cells are inversely related at
      the single cell level. However, demonstration of ER/PR and EGF receptors in
      individual normal luminal cells shows that expression is not mutually exclusive.

PMID- 7515557
TI  - Differential expression of beta 1 integrins in nonneoplastic smooth and striated
      muscle cells and in tumors derived from these cells.
AB  - Integrins are a superfamily of transmembrane alpha beta heterodimers that play an
      important role in cell-matrix and cell-cell interactions by acting as receptors
      for extracellular matrix proteins and for cell adhesion molecules. Using
      monoclonal antibodies against beta 1, alpha 1 to alpha 6, and alpha v subunits,
      the in situ distribution pattern of beta 1 integrins was examined
      immunohistochemically in nonneoplastic smooth and striated muscle cells and in
      their tumors. Nonneoplastic smooth muscle cells were beta 1+, alpha 1+, alpha 3+,
      alpha v+ and, in diverse localizations, also alpha 5+ or even alpha 6+. The
      expression of the beta 1 chain was conserved in all leiomyomas and
      leiomyosarcomas. The distribution pattern of the alpha subunits by contrast
      underwent several changes during malignant transformation of smooth muscle cells.
      These alterations consisted in a neoexpression of alpha 2, alpha 4, and alpha 6
      as well as in an abnormal abrogation of alpha 1 and alpha 3 in some
      leiomyosarcomas. Except for the absence of alpha 5 in the majority of epithelioid
      leiomyosarcomas, expression of the alpha 5 and alpha v subunits was mainly
      conserved. In addition, tumors with epithelioid differentiation differed from
      typical cases by the absence of alpha 1 and the simultaneous presence of alpha 4.
      Adult striated muscle cells were beta 1+ but alpha 1- to alpha 6- and alpha v-,
      whereas fetal striated muscle cells were not only beta 1+ but also alpha 3+/-,
      alpha 4+/-, alpha 5+ and alpha 6+. In all rhabdomyosarcomas the expression of
      beta 1 was retained. Furthermore, the majority of cases showed the expression of
      one or more alpha subunits most of which, ie, alpha 4, alpha 5, and alpha 6, were
      also found in fetal striated muscle cells. In conclusion, beta 1 integrins
      exhibited a differential expression pattern along the two lines of myogenic
      differentiation. This integrin profile underwent characteristic changes during
      malignant transformation. Nevertheless, the compiled distribution patterns of the
      alpha 1, alpha 3, and alpha v subunits allowed in most instances the
      discrimination between tumors of smooth (alpha 1+/alpha 3+/alpha v+) and striated
      muscle (alpha 1-/alpha 3-/alpha v-) differentiation.

PMID- 7515562
TI  - Control of H(+)-HCO3- plasma membrane transporters by urea hyperosmolality in rat
      medullary thick ascending limb.
AB  - Hyperosmolality inhibits bicarbonate absorption by the rat medullary thick
      ascending limb (MTAL) by unknown mechanisms. Intracellular pH (pHi) was monitored
      with use of 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein in rat MTAL tubule
      suspensions to specify the H(+)-HCO3- membrane transporters affected by
      hyperosmolality. Measurements were made after > or = 15-min incubation of the
      cells in media rendered hypertonic by urea to avoid any change in cell volume.
      Na(+)-H+ antiport activity, estimated from the Na(+)-induced initial rate of pHi
      recovery of Na(+)-depleted acidified cells in the presence of 0.1 mM furosemide
      to inhibit Na(+)-K(+)-2Cl- cotransport, was inhibited by 300 mM urea and 10(-8) M
      arginine vasopressin (AVP) in an additive manner. Na(+)-H+ antiport inhibition by
      urea hyperosmolality was maximal at 300 mM urea with a half-maximal inhibitory
      concentration of 75 mM and was due to a 28% decrease in maximum velocity (Vmax)
      with no effect on the Michaelis constant for sodium. Urea hyperosmolality (300
      mM) did not affect steady-state intracellular calcium concentration ([Ca2+]i),
      assessed with use of fura 2 fluorescence, and still inhibited Na(+)-H+ antiport
      in MTAL cells loaded with 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid to minimize any transient change in [Ca2+]i during the preincubation in urea
      medium. Furthermore, 300 mM urea did not stimulate basal or AVP-induced adenosine
      3',5'-cyclic monophosphate (cAMP) accumulation. Plasma membrane H(+)
      adenosinetriphosphatase (ATPase) activity and HCO3- transport, assessed by
      appropriate experimental protocols, were unaltered by 300 mM urea.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7515561
TI  - Time course of complement activation and inhibitor expression after ischemic
      injury of rat myocardium.
AB  - Activation of the complement (C) system has been documented in both experimental
      and clinical studies of myocardial infarction, but the exact time course and
      mechanisms leading to C activation have remained unclear. Our earlier postmortem
      study on human beings showed that formation of the membrane attack complex (MAC)
      of C was associated with loss of CD59 (protectin), an important sarcolemmal
      regulator of MAC, from the infarcted area. The recent discovery of a rat analogue
      of CD59 has now allowed the first experimental evaluation of the temporal and
      spatial relationship between C component deposition and loss of CD59 in acute
      myocardial infarction (AMI). After ligating the left coronary artery in rats the
      earliest sign of C activation, focal deposition of C3, was observed at 2 hours.
      Deposition of the early (C1, C3) and late pathway (C8, C9) components in the AMI
      lesions occurred at 3 hours. Glycophosphoinositol-anchored rat CD59 was expressed
      in the sarcolemmal membranes of normal cardiomyocytes. In Western blot analysis
      extracts of normal rat heart CD59 appeared as a band of 21 kd of molecular weight
      under nonreducing conditions. Loss of CD59 in the AMI lesions was observed in
      association with deposits of MAC from day one onward. Our results show that C
      activation universally accompanies AMI in vivo. It is initiated within 2 hours
      after coronary artery obstruction via deposition of C3, which may be due to
      generation of the alternative pathway C3 convertase in the ischemic area.
      Deposition of C1 and late C components also starts during the early hours (2 to 4
      hours) after ischemia. Subsequent loss of the protective CD59 antigen may
      initiate postinjury clearance of the irreversibly damaged tissue.

PMID- 7515560
TI  - Thrombospondin in human glomerulopathies. A marker of inflammation and early
      fibrosis.
AB  - Extensive damage is thought to occur to endothelial cells in renal vasculitis and
      other glomerulopathies. The state of inflammation of these endothelial cells was
      investigated through the use of a panel of monoclonal antibodies (MAb) directed
      against thrombospondin (TSP), von Willebrand factor (vWF), integrins (alpha IIb
      beta 3, alpha v beta 3), CD36, and classical markers of inflammation (P-selectin,
      E-selectin, ICAM-1, VCAM). Results show that the anti-TSP MAb (LYP10) stains
      large areas of interstitium in focal sclerosis, vasculitis, membranous
      glomerulonephritis (GN), and diabetic GN but does not in normal kidney. In
      contrast, very limited areas are stained by LYP10 in minimal change nephropathy
      and Berger's disease. On paraffin-embedded specimens these areas stained by LYP10
      appear edematous and early fibrous. Up-regulation of vWF and ICAM-1 is matched by
      an increased binding of LYP10 to the interstitium. In addition, fibrous crescents
      in injured glomeruli are stained by LYP10. This study reports for the first time
      an increased TSP secretion in glomerulopathies. Such TSP secretion may be part of
      physiological adaptive changes associated with inflammation and early fibrosis.

PMID- 7515563
TI  - Enhancement of gustatory nerve fibers to NaCl and formation of ion channels by
      commercial novobiocin.
AB  - Single fibers of the rat chorda tympani nerve were used to study the mechanism of
      action of the antibiotic novobiocin on salt taste transduction. In the rat,
      novobiocin selectively enhanced the responses of sodium-specific and amiloride
      sensitive chorda tympani nerve fibers (N type) without affecting more broadly
      responsive cation-sensitive and amiloride-insensitive fibers (E type). In the
      presence of amiloride, novobiocin was ineffective at enhancing the response of N
      type fibers toward sodium chloride. Novobiocin also increased the conductance of
      bilayers formed from neutral lipids by forming nonrectifying ion channels with
      low conductance (approximately 7 pS in 110 mM NaCl), long open times (several
      seconds and longer), and high cation selectivity. Amiloride did not alter either
      the conductance or kinetics of these novobiocin channels. These observations
      suggest that even though novobiocin is able to form cation channels in lipid
      bilayers, and possibly in cell membranes as well, its action on the salt-taste
      response is through modulation of existing amiloride-sensitive sodium channels.

PMID- 7515564
TI  - Endotoxin-stimulated alveolar macrophages impair lung epithelial Na+ transport by
      an L-Arg-dependent mechanism.
AB  - The Na+ transport function of alveolar epithelium represents an important
      mechanism for air space fluid clearance after acute lung injury. We studied the
      effect of endotoxin-stimulated rat alveolar macrophages on lung epithelial ion
      transport and permeability in vitro. Cultured rat distal lung (alveolar)
      epithelial monolayers incubated with both endotoxin and macrophages demonstrated
      a 75% decline in transepithelial resistance and a selective 60% reduction in
      amiloride-sensitive short-circuit current (Isc). Single-channel patch-clamp
      analysis demonstrated a 60% decrease in the density of 25-pS nonselective cation
      (NSC) channels on the apical membrane of epithelium exposed to both endotoxin and
      macrophages. A concurrent reduction in epithelial F-actin content suggested a
      role for actin depolymerization in mediating this effect. Incubation of
      cocultures with the methylated L-arginine (Arg) derivative NG-monomethyl-L
      arginine prevented the reduction in epithelial Isc, as did substitution of L-Arg
      with D-Arg or incubation in L-Arg-free medium. Furthermore, the stable and
      products of Arg metabolism were found to have no effect on epithelial ion
      transport. These studies show that endotoxin-stimulated alveolar macrophages
      impair distal lung epithelial ion transport by an L-Arg-dependent mechanism by
      inactivating amiloride-sensitive 25-pS NSC channels. This may represent a novel
      mechanism whereby local inflammatory cells regulate lung epithelial ion
      transport. This could affect the ability of the lung to clear fluid from the air
      space.

PMID- 7515565
TI  - Atrial natriuretic peptide enhances activity of potassium conductance in adrenal
      glomerulosa cells.
AB  - Aldosterone secretion from the adrenal glomerulosa (AG) cells is inhibited by
      atrial natriuretic peptide (ANP). Inasmuch as alterations in K+ conductance can
      modulate aldosterone secretion, the effect of ANP on intracellular K+ homeostasis
      was investigated. Intracellular K+ concentration ([K+]i) of AG cells was assessed
      by spectrofluorometry using the K(+)-sensitive dye, K(+)-binding benzofuran
      isophthalate. The resting value of [K+]i in AG cells was determined to be 120 +/-
      1.2 mM (n = 37) in a HCO3-free, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic
      acid-buffered medium. Exposure of AG cells to ANP led to a dose-dependent,
      transient decrease in [K+]i, from 21 +/- 3.2% (n = 7) at 100 pM to 31 +/- 2.3% at
      1 microM (n = 7). In the continued presence of ANP, a rapid recovery to near
      basal values of [K+]i was attained within 90 s. Measurements of membrane voltage
      using the potential sensitive dye 1-3(-sulfonatopropyl)-4-[beta-(-(di-n
      butylamino)-6-naphthyl)vinyl ]- pyridinium betaine documented an accompanying
      change in membrane potential. Pretreatment of AG cells with barium (0.5 mM),
      tetraethylammonium (0.1 mM), charybdotoxin (100 nM), or ethylene glycol-bis(beta
      aminoethylether)-N,N,N',N'-tetraacetic acid (0.5 mM) blunted the ANP-induced
      decrease in [K+]i. ANP-(7-23), the ANP-C-receptor selective agonist, which does
      not elevate guanosine 3',5'-cyclic monophosphate (cGMP) did not alter [K+]i in
      contrast to cGMP (50 microM), which did. We conclude that ANP via the activation
      of the ANP A receptor alters K+ homeostasis through a Ca(2+)-activatable K(+)
      conductive pathway likely to be the maxi-K channel.

PMID- 7515568
TI  - Detection and quantitation of EP3 prostaglandin E2 receptor mRNA along mouse
      nephron segments by RT-PCR.
AB  - mRNA of the EP3 prostaglandin E2 (PGE2) receptor was detected and quantitated in
      microdissected mouse nephron segments by a modified protocol of reverse
      transcription-polymerase chain reaction (RT-PCR). At the step of RT, a point
      mutation was introduced in cDNA, which made a new restriction site for the Mbo I
      enzyme. PCR was performed using a set of primers on the same exon, and genomic
      DNA was coamplified with cDNA by these primers. PCR products were treated with
      Mbo I, and signals from genomic DNA and mRNA were separately detected on gel
      electrophoresis. The relative amount of mRNA per cell was expressed as a ratio of
      amount of product from mRNA to that from genomic DNA. EP3 PGE2 receptor mRNA
      expression was abundant in thick ascending limb of Henle, present to a lesser
      extent in distal convoluted tubules and collecting ducts, and undetectable in
      glomeruli, proximal tubules, and descending thin limb. The results support the
      notion that PGE2 modulates water and solute transport through the EP3 receptor in
      specific structures of the kidney.

PMID- 7515567
TI  - Agonist-activated, ryanodine-sensitive, IP3-insensitive Ca2+ release channels in
      longitudinal muscle of intestine.
AB  - We have previously shown that Ca2+ mobilization in longitudinal muscle is not
      mediated by inositol 1,4,5-trisphosphate (IP3) and depends on an obligatory
      influx of Ca2+. The present study examined whether Ca2+ influx activates
      ryanodine-sensitive Ca2+ channels to cause Ca(2+)-induced Ca2+ release. Ryanodine
      bound with high affinity to longitudinal muscle cells [dissociation constant (Kd)
      7.3 +/- 0.3 nM] and microsomes (Kd 7.5 +/- 0.4 nM) and induced concentration
      dependent 45Ca2+ efflux [50% effective concentration (EC50) 1.3 +/- 0.5 nM],
      increase in cytosolic free Ca2+ (EC50 2.0 +/- 0.7 nM), and contraction (EC50 0.9
      +/- 0.2 nM) but had no effect in circular muscle cells. Ryanodine binding and
      ryanodine-induced Ca2+ release were enhanced by caffeine and inhibited by
      dantrolene and ruthenium red but were not affected by IP3 or heparin. Changes in
      Ca2+ concentration (50-500 nM) caused Ca2+ release from permeabilized
      longitudinal but not circular muscle cells loaded with 45Ca2+. The contractile
      agonist cholecystokinin-8 elicited 45Ca2+ efflux in both circular and
      longitudinal muscle cells; efflux in longitudinal muscle cells was abolished by
      Ca2+ channel blockers and by pretreatment of the cells with ryanodine.
      Pretreatment with thapsigargin abolished agonist-induced 45Ca2+ efflux in both
      cell types. We conclude that ryanodine-sensitive IP3-insensitive Ca2+ release
      channels with properties similar to those in cardiac muscle are present in
      longitudinal but not circular muscle cells of intestine and that agonist-mediated
      Ca2+ influx activates these channels, leading to Ca(2+)-induced Ca2+ release.

PMID- 7515566
TI  - Water channel vesicles from toad urinary bladder contain a family of proteins
      present in other tissues.
AB  - Antidiuretic hormone (ADH) stimulation causes the fusion and subsequent retrieval
      of cytoplasmic vesicles containing water channels (WCV) with the apical membrane
      of toad bladder granular cells. Previously, we showed that purified WCV contain
      12 major protein bands on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. To identify various WCV proteins, we screened a panel of mouse
      monoclonal antibodies and characterized an immunoglobulin G1 monoclonal antibody,
      5E5, that recognizes integral membrane WCV proteins of 38, 33, and 31 kDa.
      Immunocytochemistry and Western blot analyses show that 5E5 binds to
      multivesicular body endosomes shown previously to contain ADH water channels. In
      addition, 5E5 recognizes these proteins in selected cells of the skin, intestine,
      liver, kidney, spleen, and lung. However, 5E5 does not appear to recognize
      components of the water channel itself. We conclude that WCV contain several
      membrane proteins recognized by 5E5 that are present in certain cells of the
      other organs. Monoclonal 5E5 provides a probe to determine the structure and
      function of these endosomal proteins as well as their role in the ADH water
      permeability response.

PMID- 7515569
TI  - Differential modulation of large-conductance KCa channels by PKA in pregnant and
      nonpregnant myometrium.
AB  - Uterine excitability depends on ion channel activity, the expression of which is
      regulated by sexual hormones. We show now that the action of protein kinase A
      (PKA) on large-conductance calcium-activated K+ (KCa) channel activity also
      depends on the hormonal status. PKA-dependent phosphorylation of reconstituted
      KCa channels from midpregnant rats usually stimulated channel activity; in
      contrast, KCa channels from nonpregnant rat and human myometrium were primarily
      inhibited by this mechanism. Both effects were reversible by phosphatase
      treatment. These results suggest that one important factor modulating uterine
      contractility during pregnancy or the regular cycle may be the differential
      response of KCa channels toward PKA-induced phosphorylation.

PMID- 7515570
TI  - Both CFTR and outwardly rectifying chloride channels contribute to cAMP
      stimulated whole cell chloride currents.
AB  - From whole cell patch-clamp recordings at 35 degrees C utilizing either nystatin
      perforation or conventional methods with 5 mM MgATP in the pipette solution, it
      was demonstrated that both cystic fibrosis transmembrane conductance regulator
      (CFTR) chloride (Cl-) channels and outwardly rectifying Cl- channels (ORCC)
      contribute to adenosine 3',5'-cyclic monophosphate (cAMP)-activated whole cell Cl
      currents in cultured human airway epithelial cells. These results were similar
      whether recordings were performed on two normal human cell lines or on two cystic
      fibrosis (CF) cell lines stably complemented with wild-type CF gene. These
      results were obtained by exploiting dissimilar biophysical properties of CFTR and
      ORCC currents such as the degree of rectification of the current-voltage
      relationship, the difference in sensitivity to Cl- channel-blocking drugs such as
      4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), calixarenes, and
      diphenylamine carboxylic acid (DPC), and the opposing Cl- relative to I-
      permeabilities of the two channels. In normal cells or complemented CF cells, 8
      (4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate stimulated outwardly
      rectifying whole cell Cl- currents. Addition of DIDS in the presence of cAMP
      inhibited the outwardly rectifying portion of the cAMP-activated Cl- current. The
      remaining cAMP-activated, DIDS-insensitive, linear CFTR Cl- current was inhibited
      completely by DPC. Additional results showed that not only do ORCC and CFTR Cl-
      channels contribute to cAMP-activated Cl- currents in airway epithelial cells
      where wild-type CFTR is expressed but that both channels fail to respond to cAMP
      in delta F508-CFTR-containing CF airway cells. We conclude that CFTR not only
      functions as a cAMP-regulated Cl- channel in airway epithelial cells but also
      controls the regulation of ORCC.

PMID- 7515571
TI  - Hyperabsorption of Na+ and raised Ca(2+)-mediated Cl- secretion in nasal
      epithelia of CF mice.
AB  - We investigated the effect of homozygous genetic disruption of the murine cystic
      fibrosis transmembrane regulator (CFTR) gene on regulation of the rates of Na+
      absorption and Cl- secretion by nasal epithelia in cystic fibrosis (CF) mice. The
      basal in vivo nasal potential difference (PD; -28.8 +/- 1.8 mV, n = 10) and
      amiloride-sensitive PD (delta 13.8 +/- 1.0 mV, n = 10) were raised in CF mice
      compared with controls [-7.8 +/- 0.8 mV, n = 14 (basal); delta 4.5 +/- 0.7 mV, n
      = 14 (amiloride)], consistent with raised Na+ transport. In vitro studies of
      freshly excised nasal epithelia confirmed that CF epithelia exhibited a greater
      basal equivalent short-circuit current (Ieq; 63.5 +/- 12 microA/cm2, n = 15) vs.
      control (30.2 +/- 7.2 microA/cm2, n = 16) and amiloride-sensitive Ieq (delta 46.2
      +/- 12.5 microA/cm2) vs. control (delta 11.3 +/- 4.5 microA/cm2). Tissue from
      normal mice failed to secrete Cl- in response to ionomycin (delta Ieq: -1.2 +/-
      1.9 microA/cm2, n = 18), whereas CF murine tissue responded with a large rise in
      Ieq (delta 55.1 +/- 19.1 microA/cm2, n = 13). We conclude that CF murine nasal
      epithelia exhibit Na+ hyperabsorption, providing strong evidence for a regulatory
      link between CFTR and Na+ channel activity in airway epithelia. We speculate that
      upregulation of the Ca(2+)-mediated Cl- secretory pathway buffers the severity of
      airway disease in the CF mouse.

PMID- 7515573
TI  - Pancreatic enzyme synthesis and turnover in human subjects.
AB  - Animal studies have shown that pancreatic enzyme secretion is independent of
      enzyme synthesis. To investigate this relationship in humans, we have coinfused
      14C-labeled leucine tracer with cholecystokinin octapeptide in nine healthy
      adults for 4 h and measured the rate of appearance of secreted and newly labeled
      enzymes in the duodenum. Enzyme secretion was well maintained throughout, but
      newly labeled enzymes only appeared in juice between 75 and 101 min (median time,
      86 min), indicating that initial secretion was dependent on the release of
      zymogen stores and that the median production time for new enzymes was 86 min.
      Between 85 and 225 min there was a curvilinear increase in the enrichment of
      secreted enzymes with newly synthesized enzymes, suggesting a median turnover
      rate of zymogen stores of 29%/h (range 12-47%/h). In conclusion, our results
      suggest that in healthy humans, postprandial pancreatic enzyme secretion is
      maintained by the export of a large stored pool and is not rate limited by enzyme
      synthesis, since it takes approximately 86 min for newly synthesized enzymes to
      take part in the digestive process.

PMID- 7515574
TI  - Smooth muscle cells from guinea pig stomach possess high-affinity galanin
      receptors that mediate relaxation.
AB  - Galanin-like immunoactivity occurs in nerves and plexi in muscle layers
      throughout gastrointestinal tract including the stomach. Galanin can affect
      gastric emptying and contraction or relaxation of gastric muscle in different
      species. The aim of this study was to investigate the direct effect of galanin on
      dispersed gastric smooth muscle cells and to characterize any galanin receptors
      that mediated any effect. Dispersed gastric smooth muscle cells were prepared
      from guinea pig stomach by collagenase digestion. Porcine galanin (p-galanin; 1
      microM) did not stimulate contraction when present alone; however, p-galanin (1
      microM) inhibited carbachol-induced contraction with a half-maximal effect at 7
      nM. p-Galanin (1 microM) increased cellular adenosine 3',5'-cyclic monophosphate
      (cAMP) content by 10 s and caused a maximal increase of 80% over basal. 125I
      galanin (porcine) bound to dispersed cells in a time- and temperature-dependent
      manner. Binding was saturable, reversible, and specific. Binding of 125I-galanin
      was inhibited almost equally by porcine and rat galanin (Ki = 6-8 nM) but was not
      inhibited by the galanin-associated peptide [preprogalanin-(108-123)]. The
      fragment galanin-(1-16) was equally potent to rat galanin; however, the fragment
      galanin-(9-29) was 56-fold less potent (Ki = 370 nM). Computer analysis
      demonstrated there were two binding sites for p-galanin on gastric smooth muscle
      cells, a high-affinity site (Kd = 2.6 nM) with low capacity (Bmax = 175 fmol/mg
      protein) and a low-affinity site (Kd = 150 nM) with large capacity (Bmax = 3,611
      fmol/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515575
TI  - Structural and molecular changes in intestinal smooth muscle induced by
      Trichinella spiralis infection.
AB  - Infection with Trichinella spiralis in the rat causes altered intestinal motility
      and jejunal smooth muscle contractility by day 6 postinoculation. The purpose of
      this study was to determine structural and molecular changes in the smooth muscle
      that could account for the functional changes that have been reported. By day 6
      postinoculation, there was an increase in thickness of both muscle layers of the
      jejunum. This increase in mass was accompanied by an increase in total protein
      content of the seromuscular tissues. When specific proteins were analyzed,
      increases in actin and myosin heavy chain contents were found. On the other hand,
      there was no increase in collagen content. Alterations in gene expression at the
      pretranslational level were determined by monitoring total RNA and the proportion
      of mRNA that codes for alpha-smooth muscle actin. There was an increase in both
      parameters in longitudinal muscle from the jejunum of infected animals. The
      increase appeared to be site selective because there were no increases in either
      parameter in longitudinal muscle of the distal intestine. These results indicate
      that pretranslational upregulation of gene expression for actin isoforms occurs
      in smooth muscle of the proximal but not distal intestine during the early
      enteric phase of infection with T. spiralis. Thus the altered smooth muscle
      contractility that has been reported in experimental trichinosis may be related
      in part to an increased expression of smooth muscle protein.

PMID- 7515576
TI  - TRH and substance P independently affect gastric motility in nucleus raphe
      obscurus of the rat.
AB  - The purpose of this study was to investigate whether there exists a functional
      interaction between thyrotropin-releasing hormone (TRH) and substance P (SP) in
      the nucleus raphe obscurus (NRO) in their effects on gastric motor function. This
      was accomplished by microinjection of TRH (6-45 pmol) and SP (10 and 135 pmol)
      into the NRO alone and then either as a mixture or in rapid sequential order in
      alpha-chloralose-anesthetized rats, while intragastric pressure and pyloric and
      greater curvature motility were monitored. TRH (15 and 45 pmol) evoked
      significant increases in gastric motor activity, whereas SP (135 pmol) elicited
      decreases in intragastric pressure. SP at a dose of 10 pmol was ineffective alone
      in altering gastric motor function. Microinjection of a mixture of TRH (15 pmol)
      and SP (10 pmol) into the NRO resulted in significant increases in intragastric
      pressure, pyloric motility, and greater curvature motility; these changes in
      gastric motor function were similar to the effect of TRH (15 pmol) alone. A
      mixture of TRH (15 pmol) and SP (135 pmol) resulted in changes in gastric motor
      activity that were significantly less than the effect of TRH (15 pmol)
      microinjected into the NRO alone and appeared to be an additive effect of each
      peptide. The results of sequential microinjections of both peptides were
      consistent with these findings. The stimulative effect of TRH (15 and 45 pmol) on
      intragastric pressure, microinjected into the NRO 30 s after SP (135 pmol), did
      not differ from the effect of TRH microinjected at the same doses after
      vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515572
TI  - Regulation of porcine insulin-like growth factor I and growth hormone receptor
      mRNA expression by energy status.
AB  - Regulation of insulin-like growth factor I (IGF-I) and growth hormone (GH)
      receptor mRNA in liver and muscle by energy status was assessed in 2-mo-old pigs
      by altering thermoregulatory demand and energy intake over a 5-wk period to
      produce a range of plasma IGF-I concentrations from 3.5 +/- 0.7 to 28.9 +/- 6.2
      nmol/l. These values were related directly to growth rates (0.06 +/- 0.02 to 0.44
      +/- 0.01 kg/day) and total hepatic IGF-I mRNA levels. Increased growth rates were
      accompanied by an increase in hepatic class 1 and class 2 IGF-I mRNA levels and
      an increase in the ratio of class 2 to class 1 IGF-I mRNA in liver, suggesting a
      distinct role for class 2 expression in the endocrine growth response. High
      levels of class 1 transcripts and a virtual absence of class 2 transcripts
      characterized all muscle tissues examined, and there was no correlation with
      plasma IGF-I levels. This suggests that growth promotion in response to increased
      energy status is regulated via endocrine hepatic IGF-I rather than via a
      paracrine response. The levels of GH receptor mRNA were positively correlated
      with overall growth rate (P < 0.005) in liver and negatively correlated (P <
      0.05) in muscle, indicating distinct tissue-specific effects of energy status.

PMID- 7515577
TI  - Upregulation of secretin receptor gene expression in rat cholangiocytes after
      bile duct ligation.
AB  - Secretion stimulates ductular bile secretion by binding to receptors on
      intrahepatic bile duct epithelial cells (i.e., cholangiocytes). In the rat, this
      choleretic effect increases after bile duct ligation (BDL). Although
      cholangiocyte proliferation induced by BDL contributes to secretin-induced
      hypercholeresis, the mechanisms modulating these alterations in secretin-induced
      ductular bile secretion are obscure. Thus we studied the expression of secretin
      receptor mRNA (SR-mRNA) in purified liver cells from normal and BDL rats.
      Northern blot analysis and RNase protection assays with mRNA from purified liver
      cells demonstrated SR-mRNA only in cholangiocytes; moreover, SR gene expression
      showed a seven- to ninefold increase in individual cholangiocytes from BDL rats
      compared with controls. This increase in SR-mRNA expression was related to a
      similar increase in the rate of transcription of SR-mRNA in cholangiocytes from
      BDL rats. Thus our studies indicate that 1) SR-mRNA is detected in liver only in
      cholangiocytes; 2) BDL causes an increase in SR-mRNA in individual
      cholangiocytes; and 3) the increase in SR-mRNA after BDL is partly related to an
      increase in the rate of transcription of SR-mRNA by cholangiocytes after BDL. Our
      data suggest that upregulation of the SR gene may contribute to secretin-induced
      hypercholeresis.

PMID- 7515578
TI  - Calu-3: a human airway epithelial cell line that shows cAMP-dependent Cl-
      secretion.
AB  - Of 12 cell lines derived from human lung cancers, only Calu-3 cells showed high
      transepithelial resistance (Rte) and increases in short-circuit current (Isc) in
      response to mediators. Calu-3 cells formed polarized monolayers with tight
      junctions and Rte of approximately 100 omega.cm2. Baseline Isc was approximately
      35 microA/cm2 and was increased by approximately 75 microA/cm2 on elevation of
      intracellular adenosine 3',5'-cyclic monophosphate (cAMP) by isoproterenol. Flux
      studies showed that the increase in Isc was due to Cl- secretion. Forskolin and
      permeant analogues of cAMP also increased Isc. Consistent with the presence of
      cAMP-dependent Cl- secretion, immunoprecipitation demonstrated the presence of
      the cystic fibrosis transmembrane conductance regulator (CFTR). Bradykinin,
      methacholine, trypsin, and histamine all transiently (15-30 s) elevated Isc,
      probably by increasing intracellular Ca concentration. Experiments in which the
      basolateral membrane was permeabilized with nystatin indicated that CFTR was
      substantially activated under baseline conditions and that Ca-activated Cl-
      channels were absent from the apical membrane. We anticipate that Calu-3 cells
      will prove useful in the study of Cl- secretion and other functions of human
      airway epithelial cells.

PMID- 7515579
TI  - CFTR in Calu-3 human airway cells: channel properties and role in cAMP-activated
      Cl- conductance.
AB  - Calu-3, a cell line derived from a lung adenocarcinoma, forms tight junctions,
      expresses cystic fibrosis transmembrane conductance regulator (CFTR), and
      secretes Cl- in response to adenosine 3',5'-cyclic monophosphate (cAMP)-elevating
      agents. Anion conductance of Calu-3 cells was assessed with isotopic flux and
      patch-clamp methods at 22 degrees C. Iodide efflux was increased by cAMP
      elevating agents and brief trypsin treatment. A 7.1 +/- 0.4-pS voltage
      independent Cl- channel with linear current-voltage relation was the most common
      channel observed in cell-attached recordings and was identified as CFTR on the
      basis of shared features with recombinant CFTR. In unstimulated cells, the mean
      minimum number of active CFTR channels per patch was 1 +/- 1 (n = 12), increasing
      to 6 +/- 8 (n = 40) after stimulation with cAMP-elevating agents or after brief
      trypsin treatment. Channel closure after excision was biexponential with tau 1
      approximately 4 s and tau 2 approximately 79 s; typically channels were open
      continuously until closing permanently. In 11 of 12 excised patches, channels
      were reactivated by exposure to cAMP-dependent protein kinase (PKA) plus ATP.
      Efficacy of reactivation was inversely related to the duration from excision to
      addition of PKA. Channels were blocked by 20-40 microM 5-nitro-2-(3
      phenylpropylamino)benzoate on cytosolic but not external side. Active CFTR
      channels were recorded in 83% of total patches. Other types of Cl- channels were
      observed in 5 of 52 (10%) cell-attached patches and in 17 of 34 (50%) excised
      patches, including an outwardly rectifying channel in 2 patches. CFTR channels
      are the predominant pathway for cAMP-stimulated Cl- conductance in Calu-3 cells;
      the long open times in the absence of ATP are not explained by present models of
      CFTR activation.

PMID- 7515581
TI  - Potential-induced changes in intracellular pH.
AB  - In a variety of cell types and tissues there is a strong dependence of
      intracellular pH (pHi) on membrane potential (Vm). Since cell Vm values can be
      altered by hormones, ion concentrations, and changes in membrane conductances,
      the potential-dependent changes in pHi may serve as an important mechanism by
      which cells can alter their pHi to an environmental stimulus. The H+ flux across
      the cell membranes is thought to take place via putative H+ channels that are
      blocked by low concentrations of divalent metal ions. However, in Na(+)
      transporting epithelia, a major part of the H+ flux seems to be via the amiloride
      sensitive apical Na+ channels, which are not sensitive to divalent metal ions.
      The H+ flux via the Na+ channels can be modulated by natriferic hormones and
      intracellular second messengers. The H(+)-conductive pathways may play an
      important role in signal transduction in some cells.

PMID- 7515580
TI  - Identification of PDE isozymes in human pulmonary artery and effect of selective
      PDE inhibitors.
AB  - The effects of the nonselective phosphodiesterase (PDE) inhibitor 3-isobutyl-1
      methylxanthine (IBMX) and the selective PDE inhibitors motapizone (type III),
      rolipram (type IV), zardaverine (type III/IV), and zaprinast (type V and I) on
      prostaglandin F2 alpha (PFG2 alpha)-induced tone in human pulmonary arteries was
      investigated. Relaxation was achieved by IBMX [concentration eliciting 50% of
      maximum response (EC50): 11.3 microM, n = 10], motapizone (EC50:3.0 microM, n =
      7), zardaverine (EC50: 3.2 microM, n = 9), and zaprinast (EC50: 31.8 microM, n =
      6), whereas rolipram was almost ineffective. The combination of motapizone and
      zaprinast (10 microM) was the most effective relaxant with supra-additive
      relaxation and a motapizone EC50 of 575 nM. Biochemical studies revealed the
      presence of the PDE isozymes I, III, IV and V in the cytosolic and particulate
      phases of arterial homogenates; PDE II was not detectable. Partial inhibition of
      adenosine 3',5'-cyclic monophosphate (cAMP)-hydrolyzing PDE activity was achieved
      with rolipram (26 +/- 2.2%) or motapizone (60 +/- 5.4%), whereas there was almost
      complete inhibition of total PDE activity with zardaverine (81 +/- 2.0%) or the
      combination of motapizone and rolipram (82 +/- 2.3%). Inhibition of guanosine
      3',5'-cyclic monophosphate (cGMP)-hydrolyzing PDE activity was achieved with
      zaprinast (62 +/- 2.6%) and motapizone (13 +/- 2.3%), indicating the cGMP
      hydrolyzing activity of PDE III. We conclude that four out of the five recognized
      PDE isozyme families are present in human pulmonary artery. PGF2 alpha-induced
      tone in this tissue is effectively relaxed through PDE inhibitors with
      selectivity for type III, III/IV, and type V PDE.

PMID- 7515582
TI  - Expression of Na-P(i) cotransport in rat kidney: localization by RT-PCR and
      immunohistochemistry.
AB  - We have recently identified a rat kidney cortex Na-dependent transport system for
      phosphate (P(i)) by expression cloning (NaP(i)-2) (S. Magagnin, A. Werner, D.
      Markovich, V. Sorribas, G. Stange, J. Biber, and H. Murer. Proc. Natl. Acad. Sci.
      USA 90: 5979, 1993). In this study we have used reverse transcription-polymerase
      chain reaction (RT-PCR) and immunohistochemistry to establish the sites of
      expression of the NaP(i)-2-related mRNA and protein. RT-PCR was performed with
      single microdissected nephron segments. From these experiments we conclude that
      NaP(i)-2 mRNA is predominantly expressed in the proximal tubules of superficial
      and deep nephrons. No NaP(i)-2 mRNA was detected in the thick ascending limb of
      Henle's loop; however, faint NaP(i)-2 related PCR products were also observed in
      collecting ducts. Expression of the NaP(i)-2 protein was examined with the use of
      polyclonal antibodies raised against synthetic NaP(i)-2-derived peptides. Strong
      specific anti-NaP(i)-2 antiserum-mediated immunofluorescence was found in the
      convoluted part of proximal tubules and gradually decreased along the straight
      part. Immunofluorescence indicated that the NaP(i)-2 protein is present in the
      brush border of proximal tubular cells. In addition, NaP(i)-2-specific
      immunofluorescence was also observed in subapical vesicles. The described
      distribution of the NaP(i)-2 protein is in agreement with previously described
      nephron sites of P(i) reabsorption in the rat kidney and therefore suggests that
      the NaP(i)-2 transport system represents an Na-P(i) cotransporter involved in
      proximal tubular apical transport of phosphate.

PMID- 7515583
TI  - Fractal analysis of role of smooth muscle Ca2+ fluxes in genesis of chaotic
      arterial pressure oscillations.
AB  - We have investigated the role of vascular smooth muscle Ca2+ fluxes in the
      genesis of chaotic pressure oscillations induced by histamine in isolated
      resistance arteries from the rabbit ear. The responses exhibited distinct "fast"
      and "slow" components, with periods of 5-20 s and 1-5 min, respectively, which
      could be dissociated pharmacologically. The fast subsystem involved ion movements
      at the cell membrane and was inhibited by both low (< 2 mM) and high (> 5 mM)
      extracellular Ca2+ concentration ([Ca2+]o) by verapamil (which inhibits voltage
      dependent Ca2+ influx) and by charybdotoxin (ChTX) and apamin (which block Ca(2+)
      activated K+ channels). In contrast, the slow subsystem was intracellular and was
      selectively attenuated by ryanodine, which inhibits Ca(2+)-induced Ca2+ release
      from sarcoplasmic reticulum. The effects of these interventions on the complexity
      of the responses were quantified by calculating their fractal dimension, a
      parameter that estimates the minimum number of independent variables contributing
      to an irregular time series. Its mean value was generally > 2 under control
      conditions but decreased to < 2 in a concentration-dependent fashion in the
      presence of verapamil, ChTX, apamin, or ryanodine and when [Ca2+]o was outside
      the range of 2-3 mM. Each intervention thus removed one dimension of complexity
      from the mechanisms generating the rhythmic activity. We conclude that the
      interaction of a fast membrane oscillator, which involves Ca2+ influx, Ca(2+)
      activated K+ efflux, and therefore presumably changes in membrane potential, and
      a slow intracellular oscillator involving Ca2+ sequestration and release from
      stores is responsible for vascular chaos in our model. The coupling between these
      subsystems is likely to be mediated by cytosolic [Ca2+].

PMID- 7515584
TI  - PGD2 is an intermediate in agonist-stimulated nitric oxide release in rabbit skin
      microcirculation.
AB  - We investigated the role of endogenous prostaglandins and NO in the blood flow
      response of skin microcirculation in vivo. Test agents were injected
      intradermally in anesthetized rabbits and changes in skin blood flow measured
      with a laser-Doppler flow probe. Skin blood flow increased 75% at 7.33, 6.77,
      11.63, 10.30, 10.55, 8.20, and < 7 -log mol/site with acetylcholine, ATP,
      bradykinin, prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), NO gas in solution,
      and nitroprusside respectively. Co-injection of indomethacin (3 x 10(-9)
      mol/site) or NG-nitro-L-arginine methyl ester (L-NAME; 10(-7) mol/site) with
      either acetylcholine or bradykinin abolished the effects. This suggests a link
      between NO and prostaglandin release. Arachidonic acid increased blood flow,
      which was inhibited by indomethacin, L-NAME, or the PGD2-receptor antagonist BW
      A868C. Blood flow responses to either intradermal acetyl-choline or bradykinin,
      but not to NO in solution, were abolished by co-injection with BW-A868C. PGD2
      mediated vasodilation was abolished by L-NAME or BW-A868C, but not by
      indomethacin. There was no evidence of a link between NO and prostaglandin
      release in precontracted rabbit aortic rings in vitro. The results suggest that,
      in the microcirculation of rabbit skin, acetylcholine- and bradykinin-mediated
      vasodilation involve the arachidonic acid-PGD2-NO pathway.

PMID- 7515585
TI  - Hypertonic hydroxyethyl starch restores hepatic microvascular perfusion in
      hemorrhagic shock.
AB  - The influence of small-volume resuscitation (hypertonic saline-10% hydroxyethyl
      starch, HS/HES) on liver microcirculation (intravital fluorescence microscopy)
      was studied in a nonheparinized hemorrhagic shock model [mean arterial pressure
      (MAP) 40 mmHg for 1 h] in rats. Resuscitation was performed with Ringer lactate
      (RL, 4-fold shed volume/20 min; n = 7), 10% hydroxyethyl starch 200/0.6 (HES,
      shed volume/5 min; n = 6), or 7.2% NaCl-10% hydroxyethyl starch 200/0.6 (HS/HES,
      10% shed volume/2 min; n = 7). One hour after resuscitation, MAP increased in all
      groups, but it did not return to preshock values (P < 0.05). HES (16 +/- 2%
      nonperfused sinusoids) and HS/HES (14 +/- 2% nonperfused sinusoids), but not RL
      (24 +/- 2% nonperfused sinusoids), reduced (P < 0.05) shock-induced sinusoidal
      perfusion failure (28 +/- 3%) with restoration of leukocyte velocity in sinusoids
      (S) and postsinusoidal venules (V). Shock-induced stasis/adherence of leukocytes
      was further increased (P < 0.05) after resuscitation with RL (S, 38 +/- 6%; V, 55
      +/- 20%) and HES (S, 31 +/- 8%; V, 23 +/- 14%). In contrast, resuscitation with
      HS/HES prevented increased leukocyte stasis in sinusoids (-4 +/- 4%) as well as
      adherence to endothelial lining of postsinusoidal venules (-5 +/- 10%). We
      conclude that replacement of only 10% of actual blood loss by means of small
      volume resuscitation (HS/HES) can restore hepatic microvascular perfusion and
      prevent reperfusion-induced leukocyte stasis/adherence.

PMID- 7515587
TI  - Endothelium-dependent relaxations to adenosine in juvenile rabbit pulmonary
      arteries and veins.
AB  - We studied the actions of adenosine and its analogues 5'-(N-ethylcarboxamido)
      adenosine (NECA) and N6-cyclohexyladenosine (CHA) in pulmonary vessels isolated
      from juvenile rabbits. Pulmonary arteries relaxed in a concentration-dependent
      fashion to all three compounds. Pretreatment with the methylxanthine 8-p
      sulfophenyltheophylline shifted the concentration-response curves to adenosine
      and NECA rightward, indicating that the vasodilator effects were mediated by the
      adenosine receptor. The order of potency of adenosine compounds was NECA >
      adenosine > CHA, indicating that the A2-receptor mediates relaxations to
      adenosine in rabbit pulmonary arteries. Endothelium rubbing attenuated
      relaxations to adenosine at concentrations of < or = 3 x 10(-7) M and to all NECA
      concentrations. Inhibition of nitric oxide synthase with NG-nitro-L-arginine (L
      NNA) similarly attenuated relaxations at concentrations of < or = 3 x 10(-7) M
      for adenosine and < or = 3 x 10(-8) M for NECA. With the use of the same methods,
      a substantial endothelial contribution was additionally observed in pulmonary
      veins to the vasodilator effects of NECA. We conclude that adenosine, and the
      more specific A2-receptor agonist NECA, dilate pulmonary arteries and veins
      isolated from young rabbits via a mechanism that is partially dependent on
      endothelium-derived nitric oxide.

PMID- 7515586
TI  - Role of nitroxidergic nerve in dog retinal arterioles in vivo and arteries in
      vitro.
AB  - Functional role and anatomic location of nitroxidergic nerves were determined in
      dog retinal arteries and arterioles. Isolated retinal central arteries responded
      to nicotine with relaxations that were not influenced by atropine, timolol, or
      indomethacin and damage of the endothelium, but were abolished by hexamethonium,
      methylene blue, and oxyhemoglobin. The relaxation was abolished by NG-nitro-L
      arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and was restored by L
      arginine. Relaxations caused by NO were not affected by L-NNA. Transmural
      electrical stimulation at 5 Hz relaxed the strips; the relaxation was abolished
      by L-NNA and tetrodotoxin. In anesthetized dogs, intraarterial injections of
      nicotine dilated retinal arterioles in the fundus oculi. This effect was
      abolished by L-NNA and restored by L-arginine. Intravenous injections of L-NNA
      constricted retinal arterioles, the effect being prevented by hexamethonium.
      There were nerve bundles and fibers containing NO synthase immunoreactivity in
      the adventitia and media in the retinal artery. These findings are consistent
      with our hypothesis that NO liberated from vasodilator nerves acts as
      neurotransmitter in dog retinal arteries and arterioles, and the arteriolar
      muscle tone is regulated by vasodilator nerve activity in vivo.

PMID- 7515588
TI  - Endothelial and vascular smooth muscle responses are altered after left lung
      autotransplantation.
AB  - Left lung autotransplantation (LLA) increased the pulmonary vasoconstriction
      evoked by phenylephrine and attenuated the vasodilatation caused by acetylcholine
      or bradykinin in conscious dogs. To study the mechanisms responsible for these
      changes, pulmonary arterial rings were isolated from right (control) and left
      (LLA) lower lobes of dogs 1-26 mo after LLA and were suspended for isometric
      tension recording. Compared with control rings from the same anatomic location,
      contractions to phenylephrine were increased after LLA in rings with or without
      endothelium. In arterial rings contracted to 50% of their maximal response to
      phenylephrine, acetylcholine, bradykinin, and calcium ionophore caused
      endothelium-dependent relaxations that were reduced in LLA compared with control
      rings. In arterial rings from control and LLA lungs, relaxations to acetylcholine
      were not altered by inhibition of cyclooxygenase (indomethacin) but were reduced
      after inhibition of NO synthase [N omega-nitro-L-arginine methyl ester (L-NAME)].
      After L-NAME, there was no longer any significant difference in acetylcholine
      induced relaxation between arterial rings from control and LLA lungs. Relaxation
      to SIN-1, a NO donor, was similar in arterial rings (without endothelium) from
      control and LLA lungs. The results suggest that LLA causes an increased
      sensitivity of vascular smooth muscle to alpha 1-adrenergic activation and
      endothelial dysfunction that is mediated by a selective reduction in the activity
      of endothelium-derived relaxing factor/NO.

PMID- 7515589
TI  - Enhanced role of potassium channels in relaxations to acetylcholine in
      hypercholesterolemic rabbit carotid artery.
AB  - The effect of hypercholesterolemia for 10 wk on endothelium-dependent relaxations
      to acetylcholine was studied in isolated rings of rabbit carotid artery and
      abdominal aorta contracted with phenylephrine or elevated potassium. In these
      arteries obtained from hypercholesterolemic rabbits, endothelium-dependent
      relaxations to acetylcholine were not significantly different from those of
      normal rabbits. In normal and hypercholesterolemic arteries, partial relaxation
      persisted in the presence of NG-nitro-L-arginine methyl ester (L-NAME), which
      blocked acetylcholine-induced increases in arterial guanosine 3',5'-cyclic
      monophosphate (cGMP). Combined treatment with L-NAME and the calcium-dependent
      potassium-channel inhibitor, charybdotoxin, blocked relaxations in both groups,
      suggesting that L-NAME-resistant relaxations are mediated by an endothelium
      derived hyperpolarizing factor. Charybdotoxin alone or depolarizing potassium had
      no significant effect on normal carotid artery or normal and hypercholesterolemic
      abdominal aorta but significantly inhibited relaxations of the carotid artery
      from cholesterol-fed rabbits. The enhanced role of calcium-dependent potassium
      channels and the hyperpolarizing factor in relaxation of the hypercholesterolemic
      carotid artery suggested by these results was likely related to the fact that
      acetylcholine failed to stimulate cGMP only in that artery. These data suggest
      that endothelium-dependent relaxation in these rabbit arteries is mediated by
      nitric oxide-cGMP-dependent and -independent mechanisms. In hypercholesterolemia,
      the contribution of nitric oxide-cGMP in the carotid artery is reduced, but a
      hyperpolarizing factor and calcium-dependent potassium channels maintain normal
      acetylcholine-induced relaxation.

PMID- 7515590
TI  - Temporal analysis of the anti-inflammatory effects of decentralization of the rat
      superior cervical ganglia.
AB  - Bilateral decentralization of the superior cervical ganglia (SCG) reduced the
      pulmonary inflammation that develops 4-8 h after induction of anaphylaxis in
      Nippostrongylus brasiliensis-sensitized rats. Histamine levels in peritoneal
      lavage fluid and rat mast cell protease type II in serum were increased to
      comparable levels in sham-operated and decentralized rats. In vitro stimulation
      of alveolar macrophages (ALM) with lipopolysaccharide (LPS) provoked tumor
      necrosis factor-alpha (TNF-alpha) release that was two to three times greater
      with unchallenged decentralized rats than with sham-operated rats. However, after
      allergen challenge LPS-stimulated TNF-alpha release from ALM of sham-operated
      rats increased threefold and lasted at least 24 h, whereas with decentralized
      rats release of this cytokine actually decreased at 4 and 8 h. The increase in
      the phagocytosis and respiratory burst of circulating neutrophils seen at 4 and 8
      h after allergen challenge in sham-operated rats was reduced significantly by
      decentralization. These results suggest that the attenuation of anaphylaxis
      induced pulmonary inflammation that occurs with decentralization of the SCG is
      primarily associated with downregulation of neutrophil and macrophage functions.

PMID- 7515591
TI  - Neuropeptides in the Australian lungfish Neoceratodus forsteri: effects in vivo
      and presence in autonomic nerves.
AB  - The Australian lungfish Neoceratodus forsteri is one of the few extant species of
      a phylogenetically ancient group. Immunohistochemistry showed the presence of
      galanin-, vasoactive intestinal polypeptide (VIP)-, neurotensin-, substance P-,
      and calcitonin gene-related peptide (CGRP)-like immunoreactivities in nerve
      fibers in the heart, lung, and gut, with a coexistence of VIP-, galanin-, and
      somatostatin-like immunoreactivity in the lung and galanin- and somatostatin-like
      immunoreactivity in the gut. About 20% of the substance P-immunoreactive fibers
      in gut and lung contained CGRP-like material. Major vessels showed a sparse
      innervation. In free-swimming unanesthetized fish, neurotensin (1 nmol/kg),
      galanin (1 nmol/kg), and bombesin (10 nmol/kg) reduced the heart rate. In two
      specimens tested, the effect of neurotensin was partially antagonized by
      atropine. Galanin and bombesin reduced and cholecystokinin 8 (CCK-8-S) increased
      blood flow to the lung. Neurotensin decreased, CCK-8-S increased, and substance P
      had no effect on dorsal aortic pressure, and all three decreased flow to the gut.
      It can be concluded from the present study that the general vertebrate pattern of
      cardiovascular and visceral nervous control by several neuropeptides is present
      also in Neoceratodus.

PMID- 7515594
TI  - Short report: detection of Entamoeba histolytica and E. dispar directly in stool.
AB  - Current diagnosis of Entamoeba histolytica infection requires the direct
      microscopic identification of the parasite, a technique that is insensitive and
      cannot distinguish pathogenic E. histolytica from noninvasive E. dispar. Enzyme
      linked immunosorbent assay (ELISA) antigen detection tests were developed to
      distinguish E. histolytica from E. dispar infection in stool specimens. The ELISA
      result for E. histolytica antigen was positive in 26 of 27 E. histolytica
      positive stool specimens, three of 25 E. dispar-positive stools, and one of 30
      stools with other or no intestinal parasites, giving a specificity and
      sensitivity for the detection of E. histolytica infection of 93% and 96%,
      respectively. The assay result used to detect both E. dispar and E. histolytica
      was positive in 26 of 27 E. histolytica-positive stools, 19 of 25 E. dispar
      positive stools, and one of 30 stools negative by microscopy and culture for
      Entamoeba, giving a specificity and sensitivity of 97% and 87%, respectively.
      Because these ELISAs can be completed in several hours, they offer promise as
      rapid and sensitive means of detecting amebic infection.

PMID- 7515593
TI  - Antibodies to epitopes on merozoite and sporozoite surface antigens as serologic
      markers of malaria transmission: studies at a site in the dry zone of Sri Lanka.
AB  - Antibodies against repetitive epitopes on Plasmodium falciparum and P. vivax
      circumsporozoite (CS) proteins and epitopes on the 45-kD and 185-200-kD P.
      falciparum merozoite surface antigens were measured by radioimmunoassay in
      Weheragala, a malaria-endemic site in the dry zone of Sri Lanka. Antibodies were
      measured in sera collected in February at the end of the main malaria
      transmission season and three months later in May during the low transmission
      period. Ninety-seven percent of the sample population had antibodies to the P.
      falciparum CS repeat in February and a significant proportion possessed
      antibodies directed against all epitopes tested. Concentrations and prevalence of
      antibodies to the CS repeats decreased with time after the end of malaria
      transmission in adults and children. Similar temporal changes were observed with
      antibodies to the epitopes on merozoite surface antigens. Children 7-15 years of
      age had lower antibody concentrations against most epitopes than adults. Antibody
      concentrations to two different epitopes within the same merozoite surface
      antigen showed significant association as did antibody levels against the P.
      falciparum CS repeat and the predominant P. vivax CS repeat. However, antibody
      concentrations did not correlate with the presence of blood-stage malaria
      infections.

PMID- 7515592
TI  - Chemokines/intercrines and central regulation of feeding.
AB  - Chemokines/intercrines are structurally and functionally related cytokines that
      induce specific actions on the immune system and are released in response to
      infection, inflammation, and trauma. These pathological processes are frequently
      accompanied with food intake suppression. In the present study, the action of
      chemokines/intercrines on the regulation of feeding was investigated using the
      intracerebroventricular microinfusion of chemokine/intercrine-alpha subfamily
      members [interleukin-8 (IL-8); growth-related cytokine/melanoma growth
      stimulating activity (GRO-alpha/MGSA); platelet factor-4 (PF-4); beta
      thromboglobulin (beta-TG); and interferon-inducible protein-10 (IP-10)] and beta
      subfamily members [monocyte chemotactic protein-1/monocyte chemotactic and
      activating factor (MCP-1/MCAF); regulated upon activation normal T-cell expressed
      and presumably secreted (RANTES); macrophage inflammatory protein-1 alpha (MIP-1
      alpha); and macrophage inflammatory protein-1 beta (MIP-1 beta)]. The doses
      administered were 1.0, 20, and 100 ng/rat of the chemokine/intercrine. The
      intracerebroventricular administration of three members of the alpha-subfamily
      (IL-8, PF-4, and IP-10) and two members of the beta-subfamily (MCP-1/MCAF and
      RANTES) decreased the short-term (2-h) food intake. These effective
      chemokines/intercrines, however, were significantly less potent than IL-1 beta in
      decreasing feeding. The results support the hypothesis that only a subset of
      immunomodulators released during pathological processes may participate in the
      regulation of feeding with different potencies.

PMID- 7515597
TI  - In-tube cDNA cloning method using a biotinylated RNA probe.
AB  - We report a simple, practical method for isolating a particular cDNA from a
      single-stranded (ss) cDNA library in a tube without using a radioisotope. The
      method consists of three steps: (i) the capture of a target cDNA by a
      biotinylated RNA via intermolecular hybrid formation, (ii) the binding of the
      cDNA-RNA hybrid to an avidin-coated gel, (iii) the recovery of the target cDNA by
      degradation of the RNA under mild alkaline conditions. The effectiveness of the
      method was examined by isolating a clone carrying a metapyrocatechase gene from a
      model library. This model experiment achieved an enrichment of 4800-fold. This
      method was applied to cloning of a cDNA encoding interleukin 8 (IL-8) from a cDNA
      library prepared from phorbol myristate acetate-treated U937 cells. Using an RNA
      probe prepared from a truncated cDNA encoding IL-8, the corresponding full-length
      cDNA clones were successfully obtained.

PMID- 7515596
TI  - Detection of alginate lyase by activity staining after sodium dodecil sulfate
      polyacrylamide gel electrophoresis and subsequent renaturation.
AB  - A slab gel electrophoretic method for the study of bacterial alginate lyase has
      been developed. By incorporating alginate in acrylamide gels, the method is based
      on renaturation of the enzyme after polyacrylamide gel electrophoresis in the
      presence of sodium dodecyl sulfate, subsequent staining with cetylpyridinium
      chloride, and quantification of the spot by densitometric scanning. The molecular
      mass of alginate lyase can be determined from its position in the gel.

PMID- 7515598
TI  - Monochlorobimane does not selectively label glutathione in peripheral blood
      mononuclear cells.
AB  - Monochlorobimane (MCB) has been used by several investigators as a fluorescent
      label for quantifying glutathione (GSH) levels in human peripheral blood
      mononuclear cells (PBMC). This paper describes a biochemical evaluation of this
      approach. PBMC were incubated with MCB (10-100 microM) and the fluorescence in
      extracellular medium and cell lysates was measured. Nonlinear curves were
      obtained in both cases and no "plateau" was reached. The majority of the
      fluorescence was in the medium. Gel permeation (Sephadex G-25) of the lysate
      indicated a linear increase in protein-bimane adduct formation, reaching about
      50% of the intracellular fluorescence after 1 h. Fractionation of the
      deproteinized samples with Sephadex G-10 showed that only about one-third of the
      "low-molecular-weight" fluorescence could be ascribed to GSH-bimane, in either
      the lysate or the medium. Furthermore, about 40% of the free GSH in lysates
      appeared unbound even after 1 h of incubation. These data are in line with our
      observation of an extremely low activity in PBMCs of glutathione S-transferase
      under the conditions employed. Our findings indicate that many variables
      influence the cellular fluorescence, including the presence of alternative
      metabolic pathways for MCB and the rapid excretion of GSH-bimane out of the cell.
      This lack of specificity limits the value of MCB as a GSH probe for PBMC and
      confirms earlier suggestions that a careful biochemical evaluation is a
      prerequisite for its application to any particular cell type.

PMID- 7515599
TI  - Application of capillary electrophoresis to the post-polymerase chain reaction
      analysis of rat mRNA for gastric H+,K(+)-ATPase.
AB  - We have developed a competitive quantitative RNA/polymerase chain reaction (PCR)
      method using capillary electrophoresis in the post-PCR analysis for the
      quantitation of rat gastric H+,K(+)-ATPase mRNA. Analysis with CE allows quick
      and direct separation, evaluation, and characterization of DNA fragments similar
      in size, and it offers a convenient way of automatizing the post-PCR analysis. To
      estimate the magnitudes of different error contributions affecting the accuracy
      and reproducibility of the results, an analysis of variance was performed using
      the data obtained from quantitating mRNA levels in 10 different total RNA
      extracts from the Corpus region of Sprague-Dawley rats. The result showed that
      the reproducibility of the method of analysis was sufficient for the
      determination of H+,K(+)-ATPase mRNA levels among animals even when small
      fluctuations in RNA synthesis are to be measured. A comparison was also made of
      the mRNA levels of the beta- and alpha- subunits of H+,K(+)-ATPase, and the
      results were found to be in the same level.

PMID- 7515595
TI  - Physicochemical parameters affecting the charcoal adsorption assay for
      quantitative retinoid-binding measurement.
AB  - The different parameters affecting the accuracy and reliability of the dextran
      coated charcoal adsorption assay for characterization of retinoic acid receptors
      ligand binding activity were investigated. Using dextran-coated charcoal (DCC) at
      a final 10 mg/ml concentration, an efficient adsorption of free [3H]retinoic acid
      was observed with a yield in the range 99.2 to 99.8% for ligand concentrations
      varying from 10(-9) to 10(-4) M. Nonspecific adsorption of retinoic acid reached
      50% to polystyrene and silanized glass and 70% to uncoated glass. Results
      obtained by the DCC method and by gel-filtration assay were correlated; however,
      the DCC assay appeared easier to perform and gave more reproducible results. When
      a careful measurement of free retinoid concentration was performed, the apparent
      equilibrium dissociation constant (KD) of retinoic acid was 3.1 +/- 0.4 nM and
      the KD of CD367, a synthetic retinoid, was 1.8 +/- 0.3 nM. Optimal pH for the
      binding of [3H]retinoic acid or [3H]CD367 was in the range 7.5 to 8.5. Under the
      conditions described for the adsorption assay, bound retinoid measurement was
      linearly related to the protein concentration between 0.05 and 0.25 mg/ml. At a
      lower protein concentration, addition of bovine serum albumin exerted a
      stabilizing effect on retinoid binding, allowing an accurate measurement of the
      number of specific binding sites. Using retinoic acid as ligand, bacterial
      extracts often resulted in a level of nonspecific binding in the range 10-25%. It
      could be lowered (4-10%) when resorting to [3H]CD367.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7515601
TI  - N,N'-diethyldithiocarbamate as a stain for copper-zinc superoxide dismutase in
      polyacrylamide gels of red cell extracts.
AB  - N,N'-Diethyldithiocarbamate reacts with copper in the copper-zinc superoxide
      dismutase (EC 1.15.1.1) in polyacrylamide gels to form stable yellow-brown bands
      that are quantifiable at 448 nm. This method of examining superoxide dismutase
      has been applied to crude extracts of the enzyme obtained from red cell lysates
      from which hemoglobin has been removed by chloroform-ethanol precipitation. This
      treatment did not affect the activity and heterogeneity of purified dismutase
      added to lysates and recovered by the same method. The bands that develop in the
      dithiocarbamate-stained gels of the extracts correspond exactly to the bands of
      dismutase activity obtained with a positive activity stain using dianisidine,
      indicating that the dismutase is the only copper protein that gives rise to these
      bands. The amount of superoxide dismutase in the bands, determined by comparing
      the areas under unknown peaks to areas obtained with a standard dismutase sample,
      agrees with the amount predicted from indirect superoxide dismutase activity
      measurements. Any color in gels due to trace hemoglobin or hemoglobin degradation
      products is bleached overnight during staining with the dithiocarbamate.

PMID- 7515602
TI  - The elimination of keratin artifacts in immunoblots probed with polyclonal
      antibodies.

PMID- 7515600
TI  - Quantification of 35S-labeled proteoglycans complexed to alcian blue by rapid
      filtration in multiwell plates.
AB  - This paper describes a rapid filtration assay for the quantification of 35S
      labeled proteoglycans and/or 35S-labeled glycosaminoglycans in a large number of
      samples. Separation of 35S-labeled proteoglycans and 35S-labeled
      glycosaminoglycans from unincorporated [35S]sulfate is effected by forming
      insoluble complexes between alcian blue and the glycosaminoglycan moieties of the
      proteoglycans and then filtering the solutions through "Durapore membrane" discs
      (0.45 microns pore size) fitted in a 96-well plate. Following brief rinsing
      steps, the discs are punched out and 35S-labeled macromolecules retained on the
      membrane are then quantified by scintillation counting. In this rapid filtration
      assay, the relationship between the amount of [35S]-aggrecan applied and
      radioactivity measured was linear over a broad range of concentrations (2-800
      micrograms aggrecan/ml). The amount of 35S-labeled proteoglycans measured in
      media and 4 M guanidine HCl extracts of articular cartilage and three different
      chondrocyte culture systems (monolayer, agarose gel, and alginate bead) ranged
      between 90 and 101% of the value obtained by sieve chromatography on Sephadex G
      25. The presence in samples of unlabeled proteoglycans (up to 1 mg/ml), bovine
      serum albumin (up to 4 mg/ml), DNA (up to 20 micrograms/ml), serum (up to 30%),
      or guanidine hydrochloride at 4 M did not affect recovery of 35S-labeled
      proteoglycans measurably. CPM values obtained for 35S-labeled proteoglycans or
      35S-labeled glycosaminoglycans quantified by chromatography on Sephadex G-25 and
      the filtration assay showed a strong linear relationship (r > 0.99) irrespective
      of the type of culture medium, extract, or digest used.

PMID- 7515603
TI  - A new staining method for cyclic peptides after thin-layer chromatography.

PMID- 7515604
TI  - Recombinant allergens and diagnosis of grass pollen allergy.
AB  - To evaluate the use of recombinant allergens for the diagnosis of grass pollen
      allergies, we examined the levels of IgE antibodies specific for grass pollen as
      by immunoassays. SDS-PAGE analysis of two batches of Kentucky bluegrass pollen
      extracts demonstrated that there was considerable variability in allergen content
      of extracts, which in turn affected quantitation of specific IgE antibodies by
      different immunoassay procedures. Furthermore, the levels of IgE antibodies in
      human sera specific for a recombinant grass pollen allergen, rKBG8.3, were
      examined by enzyme immunoassay. The results demonstrated that quantitation of IgE
      antibodies specific for even one single allergen may be used to discriminate sera
      of allergic individuals with respect to IgE specific for grass pollen in general.
      A positive correlation, r = .82, was found for IgE binding of the recombinant
      allergen and the crude extracts of grass pollens. It is concluded from these
      results that a single recombinant allergen or a combination of a few major
      recombinant allergens can substitute the crude extract for in vitro as well as in
      vivo diagnostic purposes.

PMID- 7515605
TI  - Calcitonin gene-related peptide nasal provocation in humans.
AB  - Trigeminal sensory nerves release neurotransmitters such as calcitonin gene
      related peptide (CGRP), substance P, and others in human nasal mucosa. The
      effects of CGRP on nasal secretion were tested in humans in vivo by applying CGRP
      directly to nasal mucosa and then lavaging the nostrils ten minutes later.
      Concentrations of total protein, albumin, lysozyme, and orcinol-reactive
      mucoglycoconjugates were measured in lavage fluid. Calcitonin gene-related
      peptide (0.1 to 100 micrograms) did not stimulate secretion of any of these
      markers indicating that CGRP had no effect on glandular secretion or albumin
      exudation in vivo. These findings indicate that CGRP did not stimulate glands or
      endothelial cells of the vessels that regulate plasma extravasation. These data
      are consistent with previous studies that demonstrate 125I-CGRP binding sites on
      arterial vessels without detecting sites on glands or epithelium, the absence of
      effects of CGRP on glandular secretion from human nasal mucosal explants in
      vitro, and the apparently minor magnitude of sensory nerve axon responses in
      humans in vivo.

PMID- 7515606
TI  - Restoration of brain stem auditory-evoked potentials by gene transfer in shiverer
      mice.
AB  - We studied the shiverer mouse as a model for correcting hearing disorders
      resulting from genetic abnormalities of the central nervous system (CNS).
      Shiverer mice are homozygous for an autosomal recessive mutation (deletion) in
      the gene for myelin basic protein (MBP), a major protein component of the myelin
      sheath in the CNS. Under electron microscopic observation of the cochlear nerve,
      the CNS portion in shiverer mice showed hypomyelination, but the peripheral
      portion, including spiral ganglion cells, was normal. We produced MBP-transgenic
      mice by microinjection of an MBP cosmid clone into the pronucleus of fertilized
      eggs from shiverer mice. The transgenic mice were found to recover MBP levels up
      to 25% of normal. A greater number of axons in the transgenic mice were
      myelinated than in the shiverer mice, but the myelin sheath was not as thick as
      in normal controls. Every interpeak latency of brain stem auditory-evoked
      potentials was prolonged in the shiverer mice and improved in the transgenic
      mice. This study provides an example of gene therapy for hearing disorders caused
      by a CNS abnormality. We discuss some strategies for researching genetic hearing
      impairment or deafness in both animals and humans.

PMID- 7515607
TI  - Membrane potential of rat adipocytes: effect of phospholipase C, concanavalin A,
      and adenosine.
AB  - The change in transmembrane potential of rat adipocytes was measured using the
      fluorescent probe 3,3'-diethylthiadicarbocyanine iodide, diS-C2-(5). The method
      was calibrated by altering the potassium ion concentration while keeping the sum
      of potassium and sodium ions at a constant concentration of 153 mM (Bailey et al:
      Bioelectrochem. Bioenergetics 21:333-42, 1989). Two insulin-mimetic agents,
      phospholipase C from Clostridium perfringens and concanavalin A, induced a dose
      dependent hyperpolarization of rat epididymal adipocytes, like insulin. Removal
      of endogenous adenosine with adenosine deaminase or adenosine receptor blockade
      with isobutylmethylxanthine following the initiation of insulin-induced
      hyperpolarization resulted in depolarization. These same agents induced
      hyperpolarization of -6 to -8 mV when added without insulin. The replacement of
      adenosine with its analogue, N6-phenylisopropyladenosine, plus insulin
      depolarized the cells toward the transmembrane potential established by insulin, 
      2.0 mV. These studies suggest that adenosine receptor occupancy is required to
      maintain insulin-induced hyperpolarization.

PMID- 7515608
TI  - Swimming upstream: the strengths of women who survive homelessness.
AB  - A study of the strengths and personal resources of women who had overcome
      homelessness revealed that the experience of homelessness for these women was a
      temporary state of disruption resulting from an effort to free themselves from
      conditions associated with despair, such as abuse or addictions, and to search
      for a better life. Personal, interpersonal, and transpersonal categories of
      strengths were identified that enabled these women to move in a positive
      direction toward health and self-actualization. The synthesizing metaphor
      "swimming upstream" describes the stoic determination required to go against the
      overwhelming negative forces of their environment.

PMID- 7515610
TI  - Island living: the experience of loneliness in a psychiatric hospital.
AB  - The purpose of this study was to examine perceptions of loneliness among
      psychiatric patients. The sample included 12 adults receiving treatment in a
      psychiatric facility. Data consisted of audiotaped semistructured interviews. Ten
      empirical categories resulted. Further analysis of empirical data provided a
      description of psychiatric patient's experiences of loneliness. The metaphor of
      living on an island illustrated the core category. Subcategories included escape
      attempts and surviving tidal waves.

PMID- 7515609
TI  - Evaluation of the potent anti-hepatitis B virus agent (-) cis-5-fluoro-1-[2
      (hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in a novel in vivo model.
AB  - A murine model was developed to investigate the in vivo activity of anti
      hepatitis B virus (HBV) agents. Mice with subcutaneous tumors of HBV-producing
      2.2.15 cells showed reductions in levels of HBV in serum and in intracellular
      levels of HBV when the mice were orally dosed with (-) cis-5-fluoro-1-[2
      (hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (FTC). No effects on tumor size or
      alpha-fetoprotein levels were observed. FTC can selectively inhibit HBV
      replication at nontoxic doses.

PMID- 7515612
TI  - Interferon-gamma-inducible murine macrophage nitric oxide synthase: studies on
      the mechanism of inhibition by imidazole agents.
AB  - Citrulline formation by the interferon-gamma/lipopolysaccharide-inducible murine
      macrophage nitric oxide synthase is inhibited reversibly by imidazole, 1
      phenylimidazole, 4-phenylimidazole, and 2-phenylimidazole with IC50 values of 40
      microM, 6 microM, 225 microM, and > 1 mM, respectively. 1-Phenylimidazole
      inhibited the maximal velocity of citrulline formation but did not alter the
      concentration of arginine providing half-maximal activity. 1-Phenylimidazole
      inhibited citrulline formation by the murine macrophage nitric oxide synthase
      competitively versus (6R)-5,6,7,8-tetrahydro-L-biopterin (THB) with a Ki value of
      0.7 microM, but inhibited citrulline formation by Ca(2+)-calmodulin-dependent
      nitric oxide synthase from GH3 pituitary cells noncompetitively versus THB with a
      Ki value of 40 microM. Imidazole inhibited citrulline formation by the murine
      macrophage nitric oxide synthase noncompetitively versus THB with a Ki value of
      48 microM. Neither imidazole nor 1-phenylimidazole inhibited the cytochrome c
      reductase activity of murine macrophage nitric oxide synthase at concentrations
      100-fold higher than their IC50 values for inhibiting citrulline formation. The
      antifungal imidazoles miconazole, ketoconazole, and clotrimazole did not inhibit
      either citrulline formation or cytochrome c reduction by murine macrophage nitric
      oxide synthase at concentration as high as 200 microM. Ca(2+)-calmodulin
      dependent nitric oxide synthase from GH3 pituitary cells exhibited a Kact for THB
      of 80 nM, while the inducible murine macrophage nitric oxide synthase exhibited a
      Kact of 8 microM.

PMID- 7515611
TI  - Purification and characterization of the constitutive nitric oxide synthase from
      human placenta.
AB  - Human endothelial nitric oxide synthase (NOS) mRNA was detected in human
      placenta. In contrast, mRNAs for human neuronal NOS or for human inducible NOS
      were not detected in placenta. Subsequently, NOS was purified over 3800-fold from
      placental extract to greater than 80% homogeneity. A single band with an apparent
      molecular weight of 135 kDa was identified by [125I] calmodulin binding to
      proteins in a sodium dodecyl sulfate-polyacrylamide gel, which is consistent with
      the predicted size of the endothelial NOS. Furthermore, the sequence of eight
      internal peptides derived from this 135-kDa protein was identical to the
      published sequence of human endothelial NOS. As has been shown for all
      constitutive NOS isozymes, the purified NOS was absolutely dependent on calcium
      and calmodulin. NOS was also purified from human umbilical vein endothelial cells
      and, on the basis of similar kinetic parameters and dependence upon calcium and
      calmodulin, appeared to be the same as the purified placental NOS. Together,
      these data indicate that the placental NOS is the constitutive NOS isozyme from
      endothelial tissue.

PMID- 7515614
TI  - [Analysis of nuclear DNA heterogeneity of the hepatocellular carcinoma (HCC)].
AB  - To evaluate the objective proliferative activity in HCC nuclear DNA contents were
      measured by means of microspectrophotometry and at the same time the
      immunohistochemical technique using anti-PCNA antibody was employed. Surgically
      resected 26 HCCs were analyzed in terms of cell proliferative activity and
      regional heterogeneity. The analysis was performed by immunohistochemical
      demonstration of PCNA and pathologic histochemical study in formalin-fixed,
      paraffin-embedded specimens and cytophotometric measurements of nuclear DNA
      contents in fresh specimens. The results were as follows. 1) Nine HCCs showed
      regional ploidy heterogeneity. 2) PCNA labeling index and histological grade of
      the marginal area was much higher than that of the central area. From these
      results, we concluded that in the process of the HCC progression proliferative
      activity was decreased in the central area and was not decreased in the marginal
      area.

PMID- 7515613
TI  - The inhibition of the constitutive and inducible nitric oxide synthase isoforms
      by indazole agents.
AB  - Citrulline formation by Ca(2+)-calmodulin (CaM)-dependent nitric oxide synthase
      from bovine brain is inhibited reversibly by indazole, 5-nitro-, 6-nitro-, and 7
      nitroindazole with IC50 values of 2.3 mM, 1.15 mM, 40 microM, and 2.5 microM,
      respectively. Inhibition of citrulline formation by 7-nitroindazole exhibited a
      Ki value of 0.16 microM and was competitive versus both arginine substrate and
      (6R)-5,6,7,8-tetrahydrobiopterin cofactor. The NADPH oxidase activity of bovine
      brain CaM-dependent nitric oxide synthase was inhibited by 7-nitroindazole with
      an IC50 value of 0.6 microM. Citrulline formation by the interferon
      gamma/lipopolysaccharide-inducible nitric oxide synthase of murine macrophages
      (264.7 cell line) is inhibited reversibly by indazole, 5-nitro-, 6-nitro-, and 7
      nitroindazole with IC50 values of 470, 240, 56, and 20 microM, respectively.
      Inhibition of citrulline formation by 7-nitroindazole exhibited a Ki value of 1.6
      microM and was noncompetitive versus arginine substrate but competitive versus
      (6R)-5,6,7,8-tetrahydrobiopterin cofactor. None of the indazoles tested inhibited
      the cytochrome c reductase activity of either nitric oxide synthase isoform at
      concentrations up to 1000-fold higher than their IC50 values for inhibition of
      citrulline formation. These observations are consistent with the proposal that
      the indazoles exert their inhibitory actions by interaction with the heme-iron of
      nitric oxide synthase such that oxygen does not bind.

PMID- 7515615
TI  - [Microspectrophotometric analysis of nuclear DNA contents related to the presence
      of alpha-fetoprotein in human hepatocellular carcinoma].
AB  - A total of 28 surgically resected hepatocellular carcinomas, including both fresh
      smeared specimens and paraffin-embedded tissues, was stained with alpha
      fetoprotein (AFP) antibody. In all cases we measured the DNA contents using
      microspectrophotometry. In 5 cases, analyses of the nuclear DNA histogram of both
      the AFP-positive and negative cells from the same specimen were successfully
      performed. The ratio of the S-G2.M phase of the AFP-positive cells was 2.24 times
      more than that of the AFP-negative cells. In addition, not only the ratio of S
      G2.M phase cells, but also the incidence of aneuploidy pattern of AFP positive
      stained cases was higher than the negative stained cases. Histologically, the AFP
      positive cases contained various differentiated tissues more than the negative
      cases. From these results, we confirmed that AFP production was related to the
      growth of HCC, and the results suggest that AFP producing HCC have a higher
      potential for growth than AFP non-producing HCC.

PMID- 7515618
TI  - Hepatopancreatoduodenectomy for advanced gallbladder carcinoma.
AB  - OBJECTIVE: To assess the effectiveness of hepatopancreatoduodenectomy (HPD) in
      patients with advanced gallbladder carcinoma directly invading the liver and
      pancreas, generally considered to be nonresectable. PATIENTS AND METHODS: Sixty
      patients with gallbladder carcinoma admitted to our hospital from 1978 to 1992,
      of whom 55 had Nevin stage V carcinoma and 21 had resectable tumors. Of these
      patients, seven underwent HPD. The remaining 34 patients had nonresectable
      tumors. The outcomes of patients undergoing HPD and those with nonresectable
      tumors were compared and the effect on their quality of life was also analyzed.
      RESULTS: Postoperative complications occurred in five of the seven patients after
      HPD, but there were no operative deaths. The 1- and 2-year survival rates were
      57% and 28.6%, respectively, with a median survival time of 12 months. In
      contrast, the 1- and 2-year survival rates of the 34 patients with nonresectable
      tumors were both 5.8%, and the median survival time was 2 months. The median and
      mean durations of home stay after HPD were 6 and 10.5 months, respectively.
      CONCLUSION: Hepatopancreatoduodenectomy has the potential to improve both
      survival and the quality of life for carefully selected patients with advanced
      gallbladder carcinoma.

PMID- 7515616
TI  - False-positive immunostaining for muscle-specific actin on formalin-fixed tonsil.

PMID- 7515617
TI  - Bone marrow changes associated with recombinant granulocyte-macrophage and
      granulocyte colony-stimulating factors. Discrimination of granulocytic
      regeneration.
AB  - The hematopoietic growth factors recombinant human granulocyte-macrophage colony
      stimulating factor and recombinant human granulocyte colony-stimulating factor
      are associated with changes of the bone marrow. To evaluate the morphologic
      features and to differentiate them from leukemia, bone marrow specimens from 12
      patients who had been treated with one of these agents were evaluated. The bone
      marrow displayed marked promyelocytic hyperplasia and a less striking increased
      percentage of myeloblasts. In each of the 11 patients without leukemia at the
      time of bone marrow biopsy, the percentage of promyelocytes in the bone marrow
      was greater than that of myeloblasts. Cytologic features of stimulated
      regeneration included diffuse cytoplasmic hypergranulation of immature
      neutrophilic precursors that had prominent perinuclear spherical clear areas
      representing the Golgi zones. With consideration of bone marrow composition and
      careful attention to cytologic detail, the distinction of bone marrow
      regeneration from acute leukemia can be made in most patients who are being
      treated with recombinant hematopoietic growth factors.

PMID- 7515620
TI  - Increased Na+/K(+)-pump activity and adenosine triphosphate utilization after
      compound 48/80-induced histamine secretion from rat mast cells.
AB  - The Na+/K(+)-pump activity and the utilization of adenosine triphosphate (ATP)
      were studied in rat peritoneal mast cells after histamine secretion induced by
      compound 48/80. We measured the ouabain-sensitive K(+)-uptake by a radioactive
      technique (86Rb+). The ATP content and the glycolytic ATP-production were
      measured by the bioluminescence technique (firefly lantern) and by measurement of
      the lactate production under anaerobic conditions (antimycin A, oligomycin),
      respectively. There was an increased requirement for ATP after the secretory
      response associated with an increased activity of the Na+/K(+)-pump. The
      anaerobic, but not the aerobic, pathway for ATP-synthesis was able to respond to
      the increased ATP-requirement. The ATP-requirement of the Na+/K(+)-pump was only
      partly satisfied when ATP was supplied from either the glycolytic or the
      oxidative pathway. This may indicate that the availability of ATP was the
      limiting factor for the activity of the Na+/K(+)-pump following histamine
      secretion under these conditions. It is concluded that the large increase in
      Na+/K(+)-pump activity after a secretory response is a likely explanation for the
      long lasting ATP-decrease in mast cells that follows histamine secretion.

PMID- 7515621
TI  - Effects of the potassium channel openers cromakalim and pinacidil on
      catecholamine secretion and calcium mobilization in cultured bovine adrenal
      chromaffin cells.
AB  - The effects of two K+ channel openers, cromakalim and pinacidil, on voltage
      dependent and receptor-mediated catecholamine secretion and Ca2+ mobilization in
      bovine adrenal chromaffin cells were studied to determine the role of membrane K+
      channels in the regulation of a Ca(2+)-dependent secretory process. Both
      cromakalim and pinacidil stimulated the efflux of 86Rb (used to monitor K+
      permeability) from preloaded cells. Cromakalim and pinacidil did not affect the
      catecholamine secretion induced by excessive depolarization with 56 mM K+, but
      inhibited that induced by moderate depolarization with 31 mM K+ in a
      concentration-dependent manner (1 microM-100 microM). The 31 mM K(+)-induced
      45Ca2+ influx and increase in intracellular free Ca2+ concentration [Ca2+]i were
      also inhibited by these agents at similar concentrations to those for inhibition
      of catecholamine secretion. Cromakalim and pinacidil inhibited catecholamine
      secretion, 45Ca2+ influx and increase in [Ca2+]i induced by stimulation of
      nicotinic acetylcholine (ACh) receptors with carbamylcholine. Furthermore, both
      cromakalim and pinacidil inhibited the increase in [Ca2+]i induced by
      carbamylcholine in the absence of extracellular Ca2+, which is thought to be
      mediated by muscarinic ACh receptors. On the other hand, they did not affect
      catecholamine secretion induced by Bay-K 8644, Ba2+, A23187, histamine or
      bradykinin. These results indicate that the K+ channel openers, cromakalim and
      pinacidil, selectively inhibit catecholamine secretion induced by moderate
      depolarization or by nicotinic ACh receptor stimulation by inhibiting Ca2+ influx
      and increase in [Ca2+]i. Furthermore, the results suggest that these K+ channel
      openers-sensitive membrane K+ channels are involved in the regulation of
      catecholamine secretion mainly indirectly through effects on the voltage
      dependent membrane Ca2+ channels.

PMID- 7515622
TI  - Effect of signal transduction pathways on the action of thapsigargin on rat mast
      cells. Crosstalks between cellular signalling and cytosolic pH.
AB  - Thapsigargin elicits histamine release on rat mast cells, and this effect is
      increased if cells are pretreated with thapsigargin before the addition of
      external calcium. Okadaic acid does not modify the response of mast cells to
      thapsigargin, while sodium fluoride or the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA) increases several fold the sensitivity of
      cells to thapsigargin. On the other hand, pertussis and cholera toxins inhibit
      the response to thapsigargin. Thapsigargin increases the activity of the Na(+)-H+
      exchanger, this effect being blocked by fluoride and not modified by TPA. The
      metals cadmium and lanthanum completely block the effect of TPA or thapsigargin
      on the Na(+)-H+ exchanger. The influx of 45Ca in rat mast cells is not modified
      by thapsigargin, but if cells are treated with thapsigargin before the addition
      of calcium, the influx is markedly increased in the first 2 min before returning
      to normal. Our results indicate that exocytosis is modulated by crosstalks
      between intracellular calcium, cytosolic pH and external calcium.

PMID- 7515619
TI  - Changes in serum amylase level following hepatic resection in chronic liver
      disease.
AB  - OBJECTIVE: Factors that were likely to cause hyperamylasemia following hepatic
      resection were studied. DESIGN: Case-comparison study. SETTING: Institutional
      practice. PATIENTS: Seventy-one patients who underwent hepatic resection because
      of primary or secondary liver tumors and other benign disease, and who had no
      history of pancreatitis, were divided into four groups. Patients were divided
      into groups according to the presence or absence of underlying liver disease and
      the vascular occlusion methods used during hepatic resection (Pringle maneuver or
      the hemihepatic vascular occlusion technique). The Pringle maneuver was chosen
      for patients in whom the duration of liver parenchymal transection was expected
      to be short and/or the hepatic hilum had severe adhesion precluding the safe
      dissection of the hepatic artery and portal vein. MAIN OUTCOME MEASURES: Serum
      amylase levels were measured on the preoperative day and on postoperative days 1,
      2, 4, 6, 7, 10, and 14. Preoperative liver function, operative blood loss,
      operative time, and vascular occlusion time were examined. RESULTS: Patients with
      chronic liver disease (CLD group) had high serum amylase levels during the
      preoperative and postoperative periods. Patients in the CLD group who underwent
      the Pringle maneuver (Pringle-L group) had significantly elevated postoperative
      serum amylase levels in comparison with their preoperative serum amylase levels.
      Pancreatitis developed in two patients in the Pringle-L group--one of them died.
      CONCLUSION: These results strongly suggest that prolonged complete occlusion of
      the portal vein for hepatectomy in patients with chronic liver disease has a
      serious influence on postoperative serum amylase levels.

PMID- 7515623
TI  - AIDS, alcohol, endothelium, and immunity.
AB  - Analogies are drawn between important unknowns in AIDS and alcohol research,
      related to underlying common pathogenetic mechanisms, immunodysregulation,
      cofactors, and prominent vascular manifestations. The central role of the blood
      and lymphatic vasculatures and specifically their endothelial lining in many
      facets of the immune response is reviewed. Evidence is presented that both
      alcohol and HIV (as well as other coinfecting viruses in AIDS) target and alter
      endothelial cells and the angiogenic process. These concepts are further
      illustrated by a serendipitous viral epidemic among rats on continuous long-term
      alcoholic and control nonalcoholic diets, where synergism between alcohol and
      virus appeared to underlie multiple vascular proliferative lesions in the liver.
      In AIDS and alcoholism/alcoholic liver disease (ALD), the prominent features of
      dysregulated angiogenesis point to the endothelium as a key player in
      pathogenesis of these seemingly disparate disorders and potentially in
      immunomodulation.

PMID- 7515624
TI  - Mapping tRNA and 5S RNA tertiary structures by charge dependent Fe(II)-catalyzed
      cleavage.
AB  - Chemical and enzymatic footprinting experiments have made it possible to identify
      protein binding sites in DNA and RNA, and to localize structural differences
      within nucleic acids to a resolution of a single base pair. We show here that by
      combining three reagents, Fe(II).EDTA2-, Fe(II).EDDA and Fe2+, differential maps
      of sites in RNA that vary in their local conformation and/or charge can be
      constructed. Comparison of profiles with respect to controls in the absence of a
      counterion such as Mg2+ allows analysis of sites responsive to tertiary
      structure. A single site that is labile to metals such as Pb2+ exists in
      tRNA(Phe) and a number of other tRNA's; this site is hyper-reactive to Fe(II),
      but not to the other probes. Scission induced by the neutral complex,
      Fe(II).EDDA, offers the most general measure of surface accessibility, since its
      distribution about the target molecule is insensitive to charge. Enhanced
      cleavage by Fe(II) relative to the other agents is detected at several adjacent
      sites in 5S RNA, consistent with conformational mobility. Protection at a series
      of positions in the arm formed by loops E and D with helix IV suggests further
      that at low temperature this arm interacts with loop A and helix I.

PMID- 7515625
TI  - Inhibition of eukaryote signal-regulated protein kinases by plant-derived
      catechin-related compounds.
AB  - The cladodes of Phyllocladus trichomanoides, the bark of Pseudotsuga menziesii
      and the heartwood of Acacia melanoxylon contain catechin derivatives that are
      potent inhibitors of rat brain protein kinase C. Most of these compounds are also
      inhibitors of bovine heart cyclic AMP-dependent protein kinase catalytic subunit
      and wheat Ca(2+)-dependent protein kinase. However, these compounds are either
      not inhibitors or are relatively poor inhibitors of avian myosin light chain
      kinase. The most potent protein kinase inhibitors are the procyanidin dimer,
      trimer and tetramer from the bark of Pseudotsuga menziesii. These compounds are
      among the most potent plant-derived protein kinase inhibitors yet found.

PMID- 7515626
TI  - Cell cycle dynamics of microcarrier cultures.
AB  - In anchorage-dependent cell microcarrier cultures knowledge of the cell's growth
      kinetics is necessary in order to design and successfully operate bioreactors,
      particularly on a large scale. However, in addition to growth kinetics, an
      understanding of the physiological state of the culture is also important. In
      this paper the cell cycle progression of Vero and MRC-5 microcarrier cultures
      have been observed utilizing a flow cytometer. Flow cytometry analysis enabled
      the differentiation of the various phases of the cell cycle as the culture moved
      from initial inoculation to the stationary, or confluent stage. Not only was the
      flow cytometer able to distinguish contact inhibited cells from noncontact
      inhibited cells, but the measured fraction of contact inhibition cells were found
      to be in agreement with fractions predicted from a previously developed cellular
      automation model for microcarrier cultures. Further, the data from the stationary
      phase was used to quantify the death rate in microcarrier cultures.

PMID- 7515627
TI  - [Etiology of schizophrenia: neurochemical aspects].

PMID- 7515630
TI  - How long have I got doctor?

PMID- 7515629
TI  - Correlation between ultrastructural and histochemical parameters in lymphokine
      activated killer (LAK) cells reacting with target cells in vitro.
AB  - Ultrastructural and fluorescence data allowed us to study the most important
      moments of the interaction between lymphokine-activated killer (LAK) cells
      against target cells (Chang) in vitro. The LAK cells, maintained at low doses of
      recombinant interleukin-2, were able to recognize, bind and destroy the tumoral
      cells. Before the attack, the LAK cells were characterized by a cytoplasm with a
      high ribosomes content; after the identification and the interaction cell-cell, a
      degeneration of the tumoral cell was observed. These observations allowed us to
      suppose that the interaction between the two types of cells may be mediated by a
      receptoral membrane system without the action of lytic enzymes.

PMID- 7515632
TI  - Treatment of patients with metastatic melanoma with a one day regimen of
      dacarbazine, vincristine, bleomycin and lomustine plus interferon-alpha.

PMID- 7515628
TI  - Targeted chemotherapy for unresectable primary and metastatic liver cancer.
AB  - In targeted chemotherapy, Lipiodol Ultrafluid was used as a carrier of anticancer
      drugs; these combinations were termed oily anticancer agents. Arterial injection
      therapy with these oily anticancer agents was performed in 330 patients with
      unresectable hepatocellular carcinoma (HCC) and 110 patients with unresectable
      metastatic liver cancer. The alpha-fetoprotein (AFP) level decreased in 178 of
      186 AFP-positive patients with HCC. Tumor size was reduced in 256 of 269
      evaluable patients with HCC. The treatment seemed to prolong survival and in 193
      HCC patients who were good candidates for therapy (those without Child C liver
      cirrhosis, without tumor occupying all four segments of the liver, or without
      extrahepatic spread) the 1-, 2-, and 5-year survival rates were 85, 52, and 34%
      respectively. In the 110 patients with metastatic liver cancer, the
      carcinoembryonic antigen level and tumor size were reduced. The 1-, 2-, and 5
      year survival rates of these 110 patients were 61, 32, and 22% respectively.

PMID- 7515633
TI  - On the other hand: the stereoselectivity of drug action at ion channels.
AB  - Ion channels are pharmacological receptors with specific drug binding sites.
      These binding sites define specific structure-function relationships for the
      actions of drug classes. Interpretation of these structure-function relationships
      may be complex because of state-dependent drug-channel interactions. These state
      dependent interactions determine affinity and access of drug to binding sites and
      may result in both quantitative and qualitative changes in structure-function
      relationships including stereoselectivity. A channel-active drug may exhibit
      antagonist or activator properties according to membrane potential and the
      stereoselectivity of interaction may also change with channel state.

PMID- 7515631
TI  - Prediction of survival in a hospital-based continuing care unit.
AB  - Prediction of survival can be relevant in palliative care in those units with
      selective admission policies and limited resources, for planning patient
      management and in discharge planning for those patients expected to go home. In
      this study, factors most predictive of prognosis were identified. Those factors
      shown to have no effect on survival included the performance of investigations or
      procedures, anti-cancer therapy, morphine dose on admission and original
      admitting ward. Patients admitted primarily for pain control had a significant
      survival advantage over those patients admitted for palliation of some other
      symptom. Actual survival correlated well with predicted outcome. Factors most
      predictive of relative risk of death in a multivariate analysis were dyspnoea,
      decubitus ulcers, predicted outcome, interventions and a diagnosis of lung
      cancer. When symptoms alone were analysed, dyspnoea and immobility carried the
      highest relative risk of death.

PMID- 7515634
TI  - Improvement of host defenses with hemopoietic growth factors.

PMID- 7515635
TI  - Effect of granulocyte colony-stimulating factor on chemotherapy-induced
      neutropenia in children with cancer.
AB  - We investigated the effects of recombinant granulocyte colony-stimulating factor
      (G-CSF) administration on duration of neutropenia, antibiotic therapy, and
      hospitalization days in 25 children with malignancies (Group A: 12 leukemia and
      lymphoma; Group B: 13 tumors) who were undergoing chemotherapy. We compared the
      effect of G-CSF with a control group of 21 children with equivalent diseases and
      chemotherapy that did not receive G-CSF treatment. All 25 children received 5
      micrograms/kg/day of G-CSF at the end of chemotherapy courses when absolute
      neutrophil counts were < or = 1000/mm3. The effect of G-CSF on median neutrophil
      profiles, antibiotic therapy, and hospitalization days was studied for both
      groups at the 1st and 4th cycle of chemotherapy. During both cycles, children who
      received G-CSF showed a faster rise of absolute neutrophil count (P < 0.001) and
      fewer hospitalization days (P < 0.05), and not as many received systemic
      antibiotic therapy (P < 0.0001). We conclude that G-CSF accelerates neutrophil
      recovery in chemotherapy-induced neutropenia in childhood malignancies.

PMID- 7515637
TI  - Investigation of the expression of the extracellular matrix glycoproteins
      tenascin and fibronectin during acne vulgaris.
AB  - Tenascin and fibronectin are extracellular matrix glycoproteins which can
      interact with cells and alter their capacity to adhere, migrate and proliferate.
      In contrast with fibronectin, tenascin has a restricted distribution in normal
      skin, but is induced during epidermal proliferation, and in wound healing.
      Because acne involves hyperproliferation of ductal keratinocytes, and rupture of
      the duct may occur during inflammation, the distribution of tenascin and
      fibronectin was investigated in acne lesions, and also in acne keloids. Biopsies
      obtained from patients attending the acne clinics were cryostat-sectioned and
      stained with tenascin antiserum. The extent of tenascin staining in the dermis
      around the pilosebaceous unit was measured. Tenascin was continually expressed
      around normal control pilosebaceous ducts; it was maximal around the
      acroinfundibulum, extending 20.83 +/- 9.32 microns (n = 14) into the dermis,
      compared with staining around the infrainfundibulum (11.88 +/- 3.70 microns, n =
      14). This was not significantly different from staining around normal
      pilosebaceous ducts obtained from acne patients. In non-inflamed lesions tenascin
      staining increased significantly around the infrainfundibulum to 76.88 +/- 29.97
      microns (n = 12), compared with this region in the normal follicles. The staining
      around the acroinfundibulum did not change significantly. Around inflamed lesions
      the whole of the dermis was positive for tenascin. No changes were detected in
      the staining pattern for fibronectin, which stained the whole dermis in all the
      sections tested. The keloid samples stained strongly for both extracellular
      matrix glycoproteins. Thus, increased tenascin expression appears to be
      associated with the development of acne lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515636
TI  - Expression of tenascin, biglycan and decorin in disorders of keratinization.
AB  - The distribution of three (recently discovered) extracellular matrix components
      (tenascin, biglycan and decorin) was studied in normal adult human skin and in a
      number of monogenic disorders of keratinization, using immunohistology. The
      expression of tenascin, which is sparsely distributed in normal human dermis, was
      found to be grossly increased in epidermolytic hyperkeratoses and in Darier's
      disease. Tenascin expression in three types of ichthyosis (X-linked recessive
      ichthyosis, autosomal dominant ichthyosis vulgaris, non-erythrodermic lamellar
      ichthyosis) was similar to that of normal skin. The presence of biglycan and
      decorin did not show a marked variation between the different disorders studied,
      suggesting that their expression is subject to regulatory mechanisms distinct
      from those of tenascin. The increased expression of tenascin in two disorders of
      keratinization with a hyperproliferative phenotype, lends further support to the
      hypothesis that dermal tenascin expression is increased as a result of epidermal
      hyperproliferation.

PMID- 7515638
TI  - Epithelium-lining macrophages in psoriasis.
AB  - Epithelium-lining macrophages are spindle-shaped cells which line the epidermis
      and hair follicles. We studied the distribution and phenotype of this hitherto
      neglected member of the dermal monocyte/macrophage system in 25 lesional
      psoriatic, and five normal skin biopsies. Epithelium-lining macrophages were
      inconspicuous in normal skin, whereas their number was increased in almost two
      thirds of psoriatic cases; in nine out of 25 lesional skin biopsies, these
      flattened cells formed an almost continuous single-cell row at the dermo
      epidermal junction. Immunophenotyping revealed that these cells expressed the
      leucocyte common antigen CD45, and the macrophage markers CD14, CD36 and CD4, but
      not CD11b. Epithelium-lining macrophages strongly expressed HLA-DR-antigens and
      CD11a, but lacked the Langerhans cell marker CD1, and CD34. The dermal dendrocyte
      marker factor XIIIa was expressed in only a minority of these cells. It is
      concluded that epithelium-lining macrophages represent a separate subset of
      dermal monocytes/macrophages with a distinct tissue localization and
      immunophenotype. Their restricted distribution and close association with the
      epidermis may suggest a role in the regulation of epidermal growth.
      Alternatively, the expression of several immune-associated molecules may indicate
      that epithelium-lining macrophages are involved in the antigen-dependent or 
      independent activation of T cells.

PMID- 7515639
TI  - Topical treatment of pityriasis rubra pilaris with calcipotriol.
AB  - From a clinical, histological and therapeutic point of view, psoriasis and
      pityriasis rubra pilaris share important characteristics. Recently, calcipotriol
      has been shown to be an effective treatment in psoriasis, and we report three
      patients with pityriasis rubra pilaris who showed a favourable response to
      topical therapy with calcipotriol. In one case, analysis of markers for epidermal
      growth, differentiation and inflammation revealed reduction of suprabasal
      expression of keratin 16, and the number of T lymphocytes, monocytes and
      macrophages. It is of interest that a reduction of the recruitment of cycling
      epidermal cells, which is a consistent response pattern during treatment of
      psoriasis, was not observed during treatment of pityriasis rubra pilaris.

PMID- 7515640
TI  - Integrins, ICAMs, and selectins: role and regulation of adhesion molecules in
      neutrophil recruitment to inflammatory sites.

PMID- 7515641
TI  - Selectins in leukocyte extravasation: function of a common epitope on L- and E
      selectin.

PMID- 7515642
TI  - Early-stage Hodgkin's disease: long-term results with radiotherapy alone or
      combined radiotherapy and chemotherapy.
AB  - BACKGROUND: Controversy still exists over the optimal management of early-stage
      Hodgkin's disease (HD); presentation features may have a different prognostic
      impact according to initial therapy, and long-term toxicity must be fully
      evaluated. PATIENTS AND METHODS: This study included 164 patients with stage IA
      IIA HD treated with radiotherapy (RT) alone or combined radio- and chemotherapy
      (CT) according to presenting features and their attendant prognostic
      significance. The RT group included 88 patients with favorable prognostic
      features; the combined modality group included 76 patients with one or more
      unfavorable features. In the RT group, 85% of patients received extended-mantle
      or STNI; in the combined modality group, RT consisted of mantle- (49%), extended
      mantle- (37%), and involved-field irradiation (14%); CT consisted of 6 cycles of
      MOPP before 1984; 3 cycles of ABVD were substituted for MOPP thereafter. RESULTS:
      Complete remission was obtained in 94% and 99% of patients of the RT and combined
      modality groups, respectively. The 10-year actuarial relapse-free survival (RFS)
      in the RT group was 62% and was influenced by stage (p = 0.04) and histology (p =
      0.01); in the combined modality group, RFS was 88% and was influenced by the
      presence of bulky disease. Overall survival and tumor mortality between the
      therapy groups were comparable. RT-related toxicity consisted of mediastinal
      fibrosis (8 cases), myelitis (3), hypothyroidism (2); other long-term events
      included 2 cases of acute leukemia in the combined MOPP and RT group. Altogether,
      8 of 20 patients who died were in their first complete remission. CONCLUSIONS: In
      stage IA-IIA HD, the combined modality therapy reduced the risk of relapse
      compared to radiation alone; long-term toxicity of RT was not negligible and
      relapses could occur late.

PMID- 7515643
TI  - Preliminary results of the EORTC-GPMC controlled clinical trial H7 in early-stage
      Hodgkin's disease. EORTC Lymphoma Cooperative Group. Groupe Pierre-et-Marie
      Curie.
AB  - In this phase III trial, 770 patients with clinical stage I-II Hodgkin's disease
      (HD) have been enrolled since November 1988. Preliminary results are given for
      the 605 (79%) patients who have completed their initial therapy. Patients were
      grouped according to 6 pretreatment prognostic characteristics. In the very
      favourable (VF) group, treatment consisted of mantle field alone. In the
      favourable (F) group, patients were randomized to either subtotal nodal
      irradiation (STNI), or 6 cycles of EBVP (epirubicin, bleomycin, vinblastine,
      prednisone) followed by involved-field irradiation (IF-RT). Unfavourable (U)
      patients were randomized to either 6 cycles of EBVP plus IF-RT, or to 6 cycles of
      MOPP/ABV hybrid plus IF-RT. Of the 35 VF patients, none have progressed during
      radiotherapy. Four patients relapsed and were salvaged. Three-year failure-free
      survival (FFS) was 82%; overall survival (OS) was 100%. Of the 254 F patients,
      130 were treated with STNI and 124 with EBVP plus IF-RT. At 3 years, FFS rates
      were 81% (1 progression, 14 relapses) and 79% (5 progressions, 8 relapses),
      respectively. Corresponding OS rates were 99% and 100%. Of the 316 U patients,
      160 received EBVP and 156 MOPP/ABV. At 3 years, FFS rates were 72% (18
      progressions, 20 relapses) and 88% (7 progressions, 6 relapses), respectively (p
      < 0.001). Although OS rates were identical (92%), the entry in the U-EBVP arm was
      stopped in November 1992. We conclude that a treatment strategy based on
      prognostic factors allows the use of less aggressive treatment in favourable
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515644
TI  - Cytokine efficiency in the treatment of high-grade malignant non-Hodgkin's
      lymphomas: results of a randomized double-blind placebo-controlled study with
      intensified COP-BLAM +/- rhGM-CSF.
AB  - In high-grade malignant non-Hodgkin's lymphomas (hNHL) recombinant human
      granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was evaluated as
      support to chemotherapy. In a phase III trial, 172 patients (age 18-73 years,
      stage II-IV) were risk-stratified according to LDH levels and lymphoma size and
      randomized to receive rhGM-CSF (400 micrograms) (87 patients) or placebo (85
      patients) subcutaneously days 8-14 of each cycle of an intensified COP-BLAM
      regimen. RhGM-CSF significantly reduced the length and nadir of neutropenia, the
      length of fever episodes, the frequency of all and of severe infections, and of
      hospitalization and antibiotic requirements. Complete response rates were 63% for
      all patients and 64% vs. 61% (n.s.) in the rhGM-CSF vs. the control group.
      Deviations from protocol in applied dosages of myelotoxic drugs and in cycle
      intervals maintained differed slightly in favor of the rhGM-CSF arm. However,
      there were no significant differences in overall survival between the GM-CSF
      treatment and control groups (21 vs. 23 months). Early relapse rates were
      markedly lower than in the standard-dose COP-BLAM/IMVP-16 regimen. Thus, GM-CSF
      abates toxic side effects of chemotherapy and may help to maintain dose intensity
      in high-risk hNHL.

PMID- 7515645
TI  - Cost-benefit of granulocyte colony-stimulating factor administration in older
      patients with non-Hodgkin's lymphoma treated with combination chemotherapy.
AB  - BACKGROUND: Older patients with non-Hodgkin's lymphoma (NHL) display a poorer
      response to chemotherapy and a significantly higher treatment-associated toxicity
      than do younger individuals. We investigated the potential clinical benefits and
      the cost-effectiveness of accelerated granulocyte recovery induced by recombinant
      granulocyte colony-stimulating factor (G-CSF) in patients with aggressive NHLs,
      aged 60-70 years, during treatment with a second-generation combination
      chemotherapy. PATIENTS AND METHODS: 12 consecutive patients (median age 66 years)
      treated with six to eight courses of CHVmP/VB plus subcutaneous G-CSF (5
      micrograms/kg/day) were compared with 11 consecutive subjects (median age 65
      years) who received the same chemotherapy regimen without growth factor support.
      The two groups of patients were fully comparable as to the clinicopathologic
      features. A comparative analysis of treatment costs (including hospitalization,
      antimicrobial prophylaxis and therapy, supportive and diagnostic procedures, and
      G-CSF) was also performed. RESULTS: Both the overall response rate and the
      percentage of complete remissions were comparable in the two treatment groups. In
      the control group, 32.5% of chemotherapy courses were delayed, as opposed to 19%
      in the G-CSF group (p = 0.05). The mean duration of delay for patients receiving
      or not receiving G-CSF was 10.1 and 25.9 days, respectively (p = 0.02). Grade 3
      and 4 granulocytopenia complicated 27.7% of chemotherapy courses in control
      patients and only 4.8% in subjects receiving G-CSF (p < 0.001). Similarly, severe
      infections and mucositis were significantly higher in patients receiving
      chemotherapy alone (15.6% and 3.6%, respectively) compared to the G-CSF group
      (4.8%, p = 0.01; p = 0.04, respectively). A mean of 1.1 days/course of
      hospitalization was required in the control group, as opposed to 0.2 days/course
      in patients receiving G-CSF (p = 0.05). Although overall treatment costs were
      higher in the control group, single cost of the recombinant growth factor
      exceeded by far all the other expenses in the G-CSF group, reaching a statistical
      relevance (p = 0.01). CONCLUSIONS: The inclusion of prophylactic G-CSF in the
      treatment plan for aggressive NHL in older patients appears safe and cost
      effective in view of the peculiar clinical features of aged subjects and the
      possibility of delivering effective doses of antineoplastic drugs on an
      outpatient setting.

PMID- 7515646
TI  - High-dose therapy and autologous bone marrow transplantation in first complete
      remission for adult patients with high-grade non-Hodgkin's lymphoma: the EBMT
      experience. Lymphoma Working Party of the European Group for Bone Marrow
      Transplantation.
AB  - One hundred and eighteen patients presenting with high-grade non-Hodgkin's
      lymphoma, undergoing autologous bone marrow transplantation (ABMT) in first
      complete remission (CR), have been reported to the European Group for Bone Marrow
      Transplantation (EBMT). Of these, 102 were eligible for inclusion in this study
      following review of registration forms. Patients with lymphoblastic lymphoma were
      excluded. Remission induction and high-dose regimens varied between contributing
      centres. A maintained CR was observed in 90% of patients. Early relapse was
      observed in 6%, and 4% suffered toxic deaths. With a median follow-up of 45
      months (3-112 months), the 5-year actuarial overall and progression-free
      survivals are both 70%. Nineteen (18%) patients relapsed at a median of 3.5
      months (0.25-52 months) after ABMT, only 1 achieving a further durable CR. The
      only factor with prognostic significance was histological subtype, with diffuse
      small noncleaved-cell lymphoma having a significantly worse outcome. High-dose
      therapy and ABMT has produced effective consolidation of first remission in this
      group of patients, even in those with poor prognostic features at presentation.

PMID- 7515647
TI  - Comparable prognostic factors and survival in elderly patients with aggressive
      non-Hodgkin's lymphoma treated with standard-dose adriamycin-based regimens.
AB  - We retrospectively analysed the prognostic factors at diagnosis, clinical
      response, and survival of 192 patients with newly diagnosed aggressive NHL
      treated in a single institution between 1985 and 1991. Overall, 37.5% (72/192) of
      patients were 65 years or older (average age 71 years, range 65-85 years), and
      62.5% (120/192) were under 65 years of age (average age 45, range 16-64 years).
      All patients were completely staged and had intermediate- or high-grade NHL. 127
      patients were treated on similar regimens with the same chemotherapy dose
      intensity irrespective of age. Standard-dose m-BACOD (methotrexate, bleomycin,
      Adriamycin, cyclophosphamide, vincristine, prednisone) or CHOP were used to treat
      60/72 (83%) elderly patients and 67/120 (56%) patients less than 65 years. The
      remaining younger patients were treated with more intensive regimens. There were
      no significant differences between the groups with regard to stage, histological
      grade, cell type, elevated LDH, number of extranodal sites, presence of B
      symptoms, or bulky disease. More elderly patients had a significantly (p < 0.02)
      poorer performance status (PS), with 42% (25/60) having a PS of 2 or more,
      compared to 22% (15/67) in those less than 65 years of age. Elderly patients had
      an inferior complete response rate, 65% versus 76%. However, overall response
      rates of 95% and 92% were similar. The disease-free survival at 3 years for
      complete responders in elderly patients was 74% compared to 82% in those under
      65. The comparable 3-year overall survival was 59% and 62%,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515649
TI  - Chlorambucil/prednisone vs. CHOP in symptomatic low-grade non-Hodgkin's
      lymphomas: a randomized trial from the Lymphoma Group of Central Sweden.
AB  - Two hundred fifty-nine previously untreated patients with low-grade non-Hodgkin's
      lymphomas (NHLs), Ann Arbor stages III and IV, entered a randomized multicenter
      trial comparing the therapeutic effect of chlorambucil/prednisone (ChP) vs. CHOP.
      All patients had symptomatic disease. The therapeutic aim was to achieve an
      asymptomatic state in the ChP group (n = 132), while in CHOP-treated patients (n
      = 127) the intention was to reach a complete remission (CR). The response rate
      (CR+PR at 8 months) was 36% in the ChP and 60% in the CHOP group (p < 0.01).
      Three and 5-year survival rates were 59% and 41% in the ChP group and 64% and 44%
      in the CHOP group. The corresponding median survival times were 46 and 52 months.
      After correction for intercurrent deaths, the overall 5-year survival was 49% for
      ChP and 54% for CHOP-treated patients. The differences were statistically not
      significant. The time from diagnosis to randomization (time with asymptomatic
      disease) was longer than one year in half of the patients. The median survival
      time from diagnosis was 68 months, with no differences between the treatment
      groups. In all histological subgroups (CLL, IC, CC, and CB-CC), a higher
      remission rate was seen with the CHOP regimen but with no statistically
      significant influence on survival. Comparing patients below and above 65 years of
      age, no significant difference in survival was noted between the two treatment
      groups. The results do not support the use of intensive chemotherapy as first
      line therapy in symptomatic low-grade NHL.

PMID- 7515648
TI  - Analysis of long-term results and prognostic factors among 138 patients with
      advanced Hodgkin's disease treated with the alternating MOPP/ABVD chemotherapy.
AB  - BACKGROUND: A prospective study was conducted to assess (a) the long-term results
      and toxicity of the alternating MOPP/ABVD regimen in advanced Hodgkin's disease;
      (b) the prognostic value of pretreatment variables and of drug dose intensity.
      PATIENTS AND METHODS: A total 138 consecutive patients with advanced Hodgkin's
      disease entered this study; patient selection included stages IIB (33% of total),
      IIIB (26%), IV (25%), and stages IIA-IIIA (16%) with bulky disease and pulmonary
      hilum involvement. The MOPP/ABVD program was delivered in an 8-month program;
      adjuvant radiotherapy on sites of bulky disease was delivered in 24 patients.
      RESULTS: Complete remission was obtained in 106 (77%) patients; significant
      factors for CR in univariate analysis were stage, symptoms, histology, and bone
      marrow involvement. The five-year relapse-free survival (RFS) was 83%; in a
      multivariate analysis, histology only correlated with RFS (p = 0.04). The five
      year freedom from tumor mortality and overall survival (OS) were 79% and 67%,
      respectively. An adverse prognostic significance for OS was observed for B
      symptoms and bone marrow involvement. The median percentage of relative dose
      intensity (RDI) was as follows: Adriamycin 86, mechlorethamine 85, vincristine
      73, vinblastine 84, bleomycin 79, procarbazine 74, dacarbazine 81. No significant
      association was found between RDI and clinical outcome. No severe pancytopenia or
      life-threatening complications occurred during therapy. CONCLUSIONS: Alternating
      MOPP and ABVD cured more than 65% of patients with advanced HD; acute and late
      toxicity were acceptable. Prognostic analysis defined subgroups with a lower
      chance of cure which may deserve a more intensive initial therapy.

PMID- 7515651
TI  - EORTC study of non-Hodgkin's lymphoma: phase III study comparing CHVmP-VB and
      ProMACE-MOPP in patients with stage II, III, and IV intermediate- and high-grade
      lymphoma.
AB  - In the EORTC lymphoma cooperative group, a randomized phase III study was done
      for patients with stage II, III, IV intermediate- and high-grade lymphoma. Eight
      courses of CHVmP-VB were compared to eight courses of ProMACE-MOPP. Response was
      evaluated after 8 courses. Of 430 patients entered, 346 were eligible for this
      first analysis. Additional radiotherapy was given at initial large masses or
      residual disease after three courses. Response rate was higher in the CHVmP-VB
      arm in comparison to the ProMACE-MOPP arm, 82% vs. 65% (p < 0.0005). In the
      ProMACE-MOPP arm, treatment had to be interrupted because of patient refusal in
      7% of the patients. So far there has been no significant difference in freedom
      from progression at 5 years (49% vs. 47%), relapse-free survival (59% vs. 59%),
      or overall survival (55% vs. 49%). Patients with early response at 4 courses
      showed no better RFS in comparison with late responders between 4 and 8 courses.
      The International Index, based on age, stage, SLDH, performance status, and
      number of extranodal localizations showed a good prognostic significance in this
      series of patients.

PMID- 7515652
TI  - A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in
      patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG
      8516 (Intergroup 0067), the National High-Priority Lymphoma Study.
AB  - BACKGROUND: CHOP is a four-drug, first-generation combination chemotherapy
      regimen that has cured approximately 30% of all patients with advanced stages of
      intermediate- or high-grade non-Hodgkin's lymphoma in national cooperative group
      trials. Initial single-institution studies of third-generation regimens such as m
      BACOD, ProMACE-CytaBOM, and MACOP-B suggested that 55%-60% of these patients
      might be cured. PATIENTS AND METHODS: In order to make a valid comparison between
      these regimens, the Southwest Oncology Group and the Eastern Cooperative Oncology
      Group initiated a randomized phase III comparison of CHOP vs. m-BACOD vs. ProMACE
      CytaBOM vs. MACOP-B. Endpoints of the study were response rate, time to treatment
      failure, overall survival, and severe or life-threatening toxicity. Received dose
      intensity calculations and subset analyses were also performed. RESULTS: 1138
      patients were registered on this clinical trial. Each treatment arm contained
      between 218 and 233 eligible patients. Known prognostic factors were equally
      distributed. The initial results of this study were recently published. There
      were no significant differences in either the partial or complete response rates
      between treatment arms. Now after a median follow-up of 49 months and a maximum
      follow-up of 84 months, there is still no difference in time to treatment failure
      (p = 0.40) or overall survival (p = 0.68). No subset of patients was found to
      have significantly improved survival with the third-generation regimens. The
      received dose intensity data were comparable to previously published data for
      these regimens. Fatal toxicity was 1% for CHOP, 3% for ProMACE-CytaBOM, 5% for m
      BACOD, and 6% for MACOP-B. CONCLUSION: Based on similar failure-free and overall
      survival with lower cost and lower severe toxicity, CHOP remains the standard
      chemotherapy for patients with advanced-stage, intermediate- or high-grade non
      Hodgkin's lymphoma. New treatment strategies need to be developed to improve the
      prognosis of these patients.

PMID- 7515650
TI  - Intensive conventional-dose chemotherapy for stage IV low-grade lymphoma: high
      remission rates and reversion to negative of peripheral blood bcl-2
      rearrangement.
AB  - BACKGROUND: Advanced-stage low-grade lymphoma is characterized by initial
      responsiveness to many conventional therapies but ultimate relapse. Intensive
      therapy approaches with non-cross-resistant regimens have not been extensively
      explored. The polymerase chain reaction (PCR) can be used to monitor for the
      presence of cells with rearrangement of bcl-2, and provides a sensitive and
      stringent parameter of disease activity and treatment response that may have
      clinical utility. PATIENTS AND METHODS: From 1988 to 1992, 138 evaluable patients
      were treated with 3 sequential chemotherapy regimens, as well as with interferon
      alfa 2b (IFN) in combination with corticosteroids. Nineteen patients had serial
      PCR monitoring for bcl-2 rearrangement. RESULTS: Among a subset of 58 patients
      who had an initial phase of IFN plus prednisone, the response rate was 59%,
      mostly partial remissions (PR). With the chemotherapy program, 65% have achieved
      complete remission to date, and 30% PR. By PCR analysis, 13 of 19 tested achieved
      negative status ('molecular remission'), a much higher frequency of molecular
      remission than has been seen with standard therapies, and these molecular
      remissions appear to correlate with a lower likelihood of relapse. CONCLUSIONS:
      Intensive conventional-dose chemotherapy can achieve high rates of remission,
      even when monitored by the stringent PCR technique.

PMID- 7515654
TI  - The role of radiation therapy in the management of gastric cancer.
AB  - Gastric cancer continues to be one of the most important gastrointestinal
      cancers. Despite improved surgery and resection rates of 30%-60% still most of
      the patients die of loco-regional recurrence or distant metastasis. The role of
      adjuvant and palliative treatment of gastric cancer has world-wide been assessed
      in uncontrolled and prospective studies. Many of those were insufficient with
      respect to the number of patients and inclusion of prognostic factors as
      stratification criteria. Furthermore, the radiation oncologist would have
      preferred if these studies had looked at loco-regional tumor control instead of
      response rates or overall survival. A comprehensive overview of the currently
      available data for radiation therapy in adjuvant and palliative treatment
      schedules of gastric cancer is given and the limits of these studies are
      critically discussed. Until now, there is no clear evidence of improved overall
      survival from the addition of radiation therapy. However, the data suggest
      radiation therapy might be an effective measure to reduce loco-regional
      recurrence rates and similarly increase the recurrence-free survival. For the
      next future, optimally designed phase III trials with sufficient numbers of
      patients should be initiated to assess the definite value of radiation therapy
      for gastric cancer.

PMID- 7515655
TI  - Grieving related to development: a preliminary comparison of three age cohorts of
      parents of children with intellectual disability.
AB  - It is argued that a child with intellectual disability represents an ongoing
      source of loss and grief for parents. A developmental framework was employed to
      compare three age cohorts of parents. Grief was operationalized within the
      affective, behavioural and cognitive domains. Measures of intrusive thoughts,
      avoidance behaviours, current emotional distress over reminders of time of
      diagnosis of disability, and intensity of wishing for what might have been were
      used, collectively, to reflect the parents' grief reactions. As hypothesized, the
      results indicate no significant age-related differences in the responses of 58
      parent dyads but significant gender-related differences. Mothers scored higher
      than fathers on all measures. However, on the Wishing Scale, there were no
      significant differences between fathers and mothers. It is concluded that
      grieving, as defined, is an ongoing feature of rearing a child with intellectual
      disability and is more intense for mothers than fathers. Results are discussed
      within the implications for research and practice, with particular reference to
      the merit of programmes and services which empower parents and strengthen bonds
      of partnership between parents and professionals.

PMID- 7515653
TI  - Hodgkin's disease with a mediastinal mass greater than 10 cm: results of four
      different treatment approaches.
AB  - BACKGROUND: Management of Hodgkin's disease (HD) and large mediastinal adenopathy
      (LMA) usually includes intensive chemotherapy (CT) with or without radiation
      therapy (XT) regardless of stage. PATIENTS AND METHODS: One hundred and eighteen
      evaluable patients received one of four treatment regimens: (1) 6 cycles of MOPP
      or similar CT and XT; (2) 2 of MOPP followed by XT; (3) 6 of CVPP/ABDIC
      (cyclophosphamide, vincristine, procarbazine, prednisone/doxorubicin, bleomycin,
      decarbazine, prednisone, lomustine) followed by XT; or (4) 3 of NOVP
      (mitoxantrone, vincristine, vinblastine, procarbazine) and XT. XT doses included
      30-40 Gy to areas of nodal involvement noted prior to therapy. RESULTS: Complete
      remission (CR) rates for groups 1, 2, 3, and 4 were 100%, 85%, 87%, and 96%.
      Respective 3-year freedom from progression (FFP) results were 88%, 66%, 82%, and
      88%, and 3-year freedom from tumor mortality (FTM) results were 100%, 84%, 84%,
      and 100%. The presence of B symptoms and stage IV disease was correlated with
      lower CR and 3-year FFP rates but similar 3-year survival. CONCLUSIONS: Results
      of this study suggest that patients with stage I-III Hodgkin's disease and LMA
      greater than 10 cm treated with 3 NOVP and XT have results similar to those
      obtained for a similar group of patients treated with 2 to 6 MOPP or 6 CVPP/ABDIC
      and XT. NOVP has also been reported to produce limited toxicity in this trial and
      should be considered as an alternative to MOPP or doxorubicin-containing regimens
      in treatment of patients with early-staged disease and LMA greater than 10 cm.

PMID- 7515656
TI  - Testicular germ cell tumors of adults show deletions of chromosomal bands 11p13
      and 11p15.5, but no abnormalities within the zinc-finger regions and exons 2 and
      6 of the Wilms' tumor 1 gene.
AB  - We have studied the involvement of chromosomal bands 11p13 and 11p15.5 in 15
      testicular seminomas (SE) and 18 testicular nonseminomatous germ cell tumors
      (NS). No allelic imbalances were found in 40% of the SE and 44% of the NS. Loss
      of heterozygosity (LOH) at 11p15.5 was seen in 21% of the SE and 47% of the NS;
      the corresponding frequencies for 11p13 were 47% and 44%. Both regions were
      deleted in 13% of the SE and 44% of the NS, indicating that all NS with a
      complete LOH of 11p13 also lost the 11p15.5 region. In one (out of two) SE and in
      five (out of eight) NS, this was due to at least two separate deletions. Loss of
      the whole p-arm was likely in one SE and two NS. No gross genomic changes of the
      Wilms' tumor 1 (WT1) tumor suppressor gene were found using a cDNA probe (WT33).
      Nor were aberrations found in the zinc-finger regions and exons 2 and 6 of this
      gene, using polymerase chain reaction amplification, single stranded DNA
      polymorphism analysis, and sequencing. We suggest that loss of genetic
      information from the short arm of chromosome 11, without affecting the WT1 gene
      in the regions studied, is relatively frequent but not crucial in the
      pathogenesis of testicular germ cell tumors of adults.

PMID- 7515657
TI  - Polysomy of chromosome 12 in 60 patients with non-Hodgkin's lymphoma assessed by
      fluorescence in situ hybridization: differences between follicular and diffuse
      large cell lymphoma.
AB  - Sixty consecutive evaluable specimens from patients with non-Hodgkin's lymphoma
      (NHL) were studied for the incidence of polysomy of chromosome 12 by fluorescence
      in situ hybridization (FISH) with probes for the repetitive DNA sequence in the
      centromeric region of chromosome 12. Thirty-six samples were from follicular
      lymphomas (FLs), and twenty-four were from diffuse large cell lymphomas (DLCLs).
      Fifty-two specimens (86%) were obtained by fine-needle aspiration of a diseased
      node, seven (11.6%) were from involved bone marrows, and one specimen was from a
      pleural effusion. Twelve of the thirty-six (33%) cases with FL had trisomy 12 in
      3-41% of the cells (median, 10%) (normal controls had three signals in 1.4 +/-
      0.7% of cells). Trisomy 12 was found in 62% of the patients who had had FL for
      more than 5 years. Nine of the twenty-four cases (37%) with DLCL had more than
      two copies of chromosome 12 in 4-92% of the cells (median, 78%), and all nine
      cases were of B-cell phenotype. Unlike FL cells, some DLCL cells had 4-6 copies
      of chromosome 12. In previously untreated patients, 54% of DLCLs and 26% of FLs
      had subpopulations of cells containing more than two copies of chromosome 12 (P =
      0.04). Only 2/7 cases of DLCL with polysomy 12 had rearrangement of the BCL2
      gene, indicating that the majority of DLCL cases with polysomy 12 did not result
      from histologic transformation of low grade follicular lymphomas. These data
      demonstrate that FISH of interphase cells is a sensitive method for detecting
      numerical abnormalities of chromosome 12 in NHL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515658
TI  - Germ-line and somatic mutations of the APC gene in patients with Turcot syndrome
      and analysis of APC mutations in brain tumors.
AB  - The Turcot syndrome (TS) is a rare, probably autosomal recessive, disorder
      characterized by development of primary neuroepithelial tumors of the central
      nervous system (CNS) and numerous adenomatous colorectal polyps. To examine the
      possible involvement of mutations of the APC gene, which is responsible for
      familial adenomatous polyposis (FAP), in Turcot syndrome, we examined DNAs from
      TS patients for alterations in this gene by means of ribonuclease protection
      analysis. Germ-line APC mutations were detected in each of three unrelated cases
      of TS, and additional (somatic) mutations were observed in colonic adenomas that
      had developed in one of these patients. However, no somatic mutations in APC were
      found among 91 neuroepithelial tumors (medulloblastoma, glioblastoma,
      astrocytoma, and oligodendroglioma), whether sporadic or associated with TS.
      These results suggest that the APC gene is associated with pathogenesis of one
      feature of TS, but that at least one other gene is responsible for the genesis of
      neuroepithelial tumors in the CNS.

PMID- 7515659
TI  - Detailed analysis of loss of heterozygosity on chromosome band 17p13 in breast
      carcinoma on the basis of a high-resolution physical map with 29 markers.
AB  - We have constructed a physical map of chromosome band 17p13, using 29 markers
      that had been localized to 17p13 by means of fluorescence in situ hybridization
      (FISH) and analysis by pulsed-field gel electrophoresis (PFGE). The map spans
      nearly 8 Mb of genomic DNA, and the estimated average distance between each
      marker is roughly 290 kb. The p13 band of chromosome 17 is thought to contain a
      putative tumor suppressor gene in addition and distal to TP53. Deletion mapping
      in a large number of breast carcinomas indicated that the tumor suppressor gene
      lies between the loci defined by cC117-708 (D17S878) and p144D6 (D17S34), which
      are an estimated 7 Mb apart. Our results should contribute to construction of a
      contig map of chromosome band 17p13 with cosmid and/or YAC (yeast artificial
      chromosome) clones, and to isolation of the putative tumor suppressor gene.

PMID- 7515660
TI  - Numerical chromosomal aberrations in thyroid tumors detected by double
      fluorescence in situ hybridization.
AB  - Double fluorescence in situ hybridization with DNA probes specific for the
      (peri)centromeric regions of chromosomes 3, 7, 9, 11, 12, 18, and X was performed
      on fresh isolated nuclei and frozen tissue sections prepared from 2 nodular
      hyperplasias, 2 adenomas, and 7 papillary carcinomas of the thyroid in order to
      detect numerical chromosomal changes. Numerical chromosomal aberrations were
      found in all malignant specimens examined. A consistent presence of at least two
      trisomies was detected in most cases, especially in the follicular variant
      specimens; the highest degree of trisomy was observed for chromosome 12. Isolated
      monosomies of moderate degree for different chromosomes were found in 1 adenoma
      and 2 papillary carcinomas. Severe monosomy of chromosome 9 was the only
      significant feature observed in the single metastatic papillary carcinoma.

PMID- 7515661
TI  - t(12;21): a new recurrent translocation in acute lymphoblastic leukemia.
AB  - A t(12;21)(p11-p12;q22) was detected by chromosome painting in three patients
      with acute lymphoblastic leukemia (ALL) among eight ALL cases with 12p-
      abnormalities. The three leukemias had similar immunophenotypes (DR+, CD10+,
      CD19+). Fluorescence in situ hybridization (FISH) experiments using YAC clones
      from 21q21-q22 were performed to better localize the breakpoint on chromosome 21.
      This breakpoint was localized to 21q22.2 in one patient. Although only one case
      of ALL with t(12;21) has been reported previously, the present results suggest
      that t(12;21) is a recurrent translocation in ALL.

PMID- 7515662
TI  - Recurrent cytogenetic abnormalities in squamous cell carcinomas of the head and
      neck region.
AB  - We characterized the breakpoints, gains, and losses of chromosome material in
      squamous cell carcinomas of the head and neck region from 29 patients. Cell lines
      were karyotyped in 1/3 of cases, direct preparations or early in vitro harvests
      in 1/3, and both in 1/3 of cases. GTG-banding was employed in all cases, as were
      C-banding and RBG- and AgNOR-staining in most. Some tumors were near-diploid and
      others near-tetraploid, but many had mixed populations, with diploid, tetraploid,
      and octoploid subclones representing essentially the same karyotypic pattern. The
      most frequent changes were deletions. Losses affecting 3p13-p24, 5q12-q23, 8p22
      p23, 9p21-p24, and 18q22-q23 ranged in frequency from 40% to 60% of tumors. Loss
      of the short arm of the inactive X occurred in 70% of tumors from female
      patients, and loss or rearrangement of the Y occurred in 74% of tumors from male
      patients. Loss of 18q appeared to be associated with short survival, as did the
      presence of multiple deletions. There was gain (2-5 extra copies) of 3q21-qter,
      5p, 7p, 8q, and 11q13-q23 in 28-38% of tumors. Three tumors had an hsr involving
      11q13-q21. Gain of material at 11q13 is postulated to be associated with
      amplification of the PRADI/CCND gene at that locus. A translocation between
      proximal 1p and either an acrocentric short arm or proximal 8p or 9p was observed
      in squamous cell carcinomas of the head and neck region but not in female genital
      tract tumors. No other abnormalities appeared to be site specific, suggesting a
      pattern of genetic evolution in squamous cell carcinoma that is independent of
      anatomic site.

PMID- 7515664
TI  - Deletion of chromosome arm 1p in a Merkel cell carcinoma (MCC).
AB  - A case of neuroendocrine skin carcinoma (Merkel cell carcinoma) with a deletion
      of the short arm of chromosome 1 (1p) as the sole chromosomal abnormality was
      examined. The tumor originated in the skin of the left knee of a 67-year-old man.
      Histopathologic study showed an undifferentiated small cell tumor which expressed
      neuron-specific enolase, chromogranin, and cytokeratin (CAM 5.2). Cytogenetic
      analysis of a lymph node metastasis from the groin showed a pseudodiploid cell
      population with a deletion of the short arm of chromosome 1 as the only
      abnormality: 46,XY,del(1)(p36.1). In situ hybridization with the D1Z2 probe
      specific for the terminal band of 1p confirmed the terminal deletion. This is the
      first case of Merkel cell carcinoma in which only one chromosomal abnormality has
      been observed. Loss of the terminal portion of 1p suggests that a tumor
      suppressor gene on 1p plays a role in the pathogenesis of Merkel cell carcinoma.

PMID- 7515663
TI  - Cytogenetic aberrations in 188 benign and borderline adipose tissue tumors.
AB  - Chromosome studies of lipomas have revealed an extensive cytogenetic
      heterogeneity. To investigate the frequencies of previously recognized
      cytogenetic subgroups and to find out if more recurrent rearrangements can be
      identified, we have analyzed cytogenetically short-term tissue cultures of 237
      samples from 188 adipose tissue tumors obtained from 142 patients. Only one of 58
      tumors from 18 patients with multiple lipomas (more than two tumors) had
      karyotypic changes. Among the sporadic lipomas, 20 tumors had supernumerary ring
      chromosomes of unknown origin, 55 had different aberrations involving chromosome
      segment 12q13-15, 11 had changes of 6p or chromosome 13, but no rings or 12q13-15
      changes, and 14 had various other aberrations. Ring chromosomes were found in all
      cytogenetically abnormal lipomas histologically classified as atypical and in
      nine tumors classified as typical lipoma or spindle cell lipoma. Recombinations
      between 12q13-15 and a few other bands or segments were seen more than once: 3q27
      28 (15 tumors), 2p22-24 and 2q35 (four tumors), 1p32-34 and 13q12-14 (three
      tumors), and 5q33 (two tumors). Recombinations of 12q13-15 with 2q35 and 13q12-14
      have not been described before. Of eight tumors with chromosome 13 aberrations,
      five had loss of 13q material. Aberrations of 12q13-15, 6p, and/or chromosome 13
      were found simultaneously in nine tumors. Two to four samples from the same tumor
      were investigated in 29 tumors with clonal aberrations. Thirteen of these tumors
      displayed clonal evolution, also noted in another 17 tumors in which only one
      sample had been investigated. Thus clonal evolution occurred in 30% of the tumors
      and was particularly frequent in atypical lipomas.

PMID- 7515665
TI  - DNA rearrangements and altered transcripts of the MLL gene in a human T-ALL cell
      line Karpas 45 with a t(X;11) (q13;q23) translocation.
AB  - Translocations involving chromosome band 11q23 are found in both lymphoid and
      myeloid leukemias as well as in lymphomas, in these translocations. The
      chromosomes most frequently involved in reciprocal translocations include
      chromosomes 4, 6, 9, and 19, and we and others have reported that chromosomes 1,
      2, 10, 15, 17, 18, 22, and X are also involved. In the cell line Karpas 45, which
      has a t(X;11) (q13;q23) translocation, we report here that the MLL gene is
      rearranged and that there are two altered transcripts of MLL that come from the
      der(11) chromosome.

PMID- 7515666
TI  - Silver staining nucleolar organizer region in prostate cytology.
AB  - Amongst males, the prevalence of prostate cancer is third in frequency with a
      rising incidence. As the population grows older, the number of latent cancer of
      the prostate increases. Therefore, diagnostic tools for an early detection of
      this malignancy are necessary. Silver staining of nucleolus organizer regions
      (AgNOR) is a new technique in tumour analysis. It is especially valuable as an
      addition to classical prostate cytology. A report on 90 cases of transrectal
      prostate aspiration biopsies is presented. 81 of these had a histological
      evaluation (biopsy gun) at the same time. The air-dried slides were stained
      according to Ploton et al. [10]. The AgNORs were counted and measured by means of
      an interactive image analysis system. Patients without malignancy were reliably
      classified as negative both by routine cytology as well as by AgNOR analysis. The
      sensitivity in routine tumor diagnosis was ca. 87%. In contrast, the AgNOR index
      revealed a sensitivity of 96% and a specificity of 97%. Thus, AgNOR staining
      improves differential diagnosis in inconclusive cases. Our data suggests that the
      inexpensive AgNOR analysis improves differentiation between carcinomatous and
      benign prostatic cells. It is a useful tool, in addition to routine prostatic
      cytology.

PMID- 7515667
TI  - Guidelines of AgNOR quantitation. Committee on AgNOR Quantitation within the
      European Society of Pathology.

PMID- 7515668
TI  - Technical and methodological aspects of silver staining and measurement of
      nucleolar organizer region (NOR).
AB  - In the last few years the NOR silver-staining technique has been introduced in
      tumor pathology for both diagnostic and prognostic purposes, but the lack of a
      standardized staining protocol has frequently led to misinterpretation of actual
      structures evaluated by the various authors. Recent data have demonstrated that
      AgNOR area is closely related to the whole stained nucleolar area obtained by
      prolonging the silver staining reaction beyond the optimal time for selective NOR
      visualization. In order to compare data from different laboratories, we propose
      to stain the whole nucleolus by silver and to measure the dimensions of the
      silver-stained nucleoli by image analysis.

PMID- 7515670
TI  - Measuring of AgNORs using image analysis.
AB  - A method is presented for the measurement of AgNORs in histological section using
      an image analysis system. Measurements are performed at the highest magnification
      (objective 100x) using a CCD camera. In the first step the AgNORs are segmented,
      counted and measured. In the second step the AgNOR clusters are segmented.
      Several features for the description of the AgNORs, the AgNOR clusters and their
      spatial distribution throughout the nucleus are given. As an internal reference,
      lymphocytes are used and the size features are given relative to the mean size of
      AgNORs in the lymphocytes. The reproducibility of the features was tested on a
      series of astrocytomas. This should be carried out with at least 150 tumor cells
      and 20 reference cells in order for accurate measurements.

PMID- 7515669
TI  - AgNOR quantification with special reference to staining patterns.
AB  - Silver staining of nucleolar organizer regions (AgNORs) is now widely used as a
      marker of malignancy in tumor pathology. Standardization of the AgNOR technique
      has thereby been shown to be of central importance. Basically, three types of
      AgNOR evaluation have been used: the counting method, image analysis and pattern
      recognition. Today, image analytical determination of AgNOR area per nucleus is
      considered to be the state of art method of AgNOR evaluation. In contrast,
      counting of every single AgNOR dot is laborious and less reproducible. For
      routine purposes, however, a rapid evaluation of AgNORs would be desirable. In
      order to elucidate the value of AgNOR distribution patterns systematic in vitro
      studies using four different urothelial cell lines (HU609, RT4, J82, MGHU1) were
      performed. AgNOR number (NORN) and AgNOR area (NORA) were closely related to the
      population doubling time (PDT) and increased during transition from G0/G1 to S/G2
      cell cycle phase. In addition, both parameters were significantly elevated in the
      polyploid RT4 cell line. In contrast, number and area of AgNOR cluster
      (aggregates of at least two AgNOR dots) were less significantly correlated to
      PDT. Formation of large AgNOR clusters (maximum diameter over 6 microns) was,
      however, restricted to the well differentiated cell lines (HU609, RT4) although
      PDT was almost identical in all 4 cell lines at exponential growth phase. Thus,
      NORN and NORA are not only related to cell proliferation but also to cell cycle
      phases and ploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515672
TI  - Influence of fixation and preparation on the AgNOR distribution in routinely
      processed breast cancer specimens.
AB  - AgNOR staining is mostly performed on unstained sections from paraffin-embedded
      material. This well-established application may be limited, if only a small
      biopsy or cytologic material is available. In this study, we analyzed the
      influence of different routine preparation types from histology and cytology on
      AgNOR staining results. 15 cases of ductal breast carcinoma were investigated
      using five different preparations per case: frozen sections, sections from
      formalin-fixed and paraffin-embedded, previously frozen material, sections from
      routinely formalin-fixed and paraffin-embedded fresh material, alcohol-fixed and
      air-dried cytological smears. After application of a modified combined Feulgen
      AgNOR staining technique, AgNOR quantification on 150 nuclei per specimen was
      performed by TV-image analysis. For each preparation type adequate AgNOR staining
      results were obtained. Although there were a number of statistically significant
      correlations, the median values for the mean nuclear area, the mean number of
      AgNORs per cell, the mean AgNOR area per cell and the mean AgNOR sum area per
      cell were quite different within the 5 preparation types. This means that
      results, obtained with one preparation type, may not be taken as standard for a
      different one.

PMID- 7515673
TI  - [Histological grading of ductal pancreatic carcinomas. Relationship to silver
      staining of NOR-associated proteins and to p53 immunoreactivity].
AB  - The histological grading of 29 ductal pancreatic carcinomas was compared with
      that of silver stained NOR-associated proteins and with p53 immunoreactivity. The
      AgNOR number (NZ) and AgNOR areas (NF) of 10 grade I carcinomas, 13 grade II
      carcinomas and 6 grade III carcinomas were investigated by image analysis.
      Furthermore, the protein expression of the p53 gene was examined by
      immunohistochemistry. A significant difference was found in both AgNOR parameters
      between grade I, grade II and grade III carcinomas (NZ: p < 0.01; NF: p < 0.05;
      grade I carcinomas: NZ 5.1/NF 8.2 microns 2; grade II carcinomas: NZ 6.0/NF 11.3
      microns 2 grade III carcinomas: NZ 8.4/NF 15.2 microns 2). By contrast no
      relation was found between histological grading and p53 immunoreactivity. In 56%
      of all carcinomas positive evidence was found of the p53 gene product. (6 grade I
      carcinomas, 7 grade II carcinomas, 3 grade III carcinomas). 44% of the cases were
      p53-negative (4 grade I carcinomas, 6 grade II carcinomas, 3 grade III
      carcinomas). This study demonstrates that the AgNOR technique is useful in the
      grading of ductal pancreatic carcinomas, whereas the expression of the p53 gene
      product is not.

PMID- 7515674
TI  - [Prognostic value of AgNORs in breast cancer].
AB  - Silver stained AgNORs were investigated by means of a semiautomatic image
      analysis system. Paraffin sections from 137 invasive ductal carcinomas of the
      breast were available with clinical and histological data, several DNA
      distribution parameters, and follow-up data of about 10 years (45 to 165 months).
      By means of the Chi 2-test the correlation of AgNOR features with the other
      variables was investigated. A significant correlation was found between AgNORs
      and the histological grading, and between AgNORs and most of the DNA parameters.
      Tumor size (pT) and pTNM-stage showed significant correlation with one of the
      AgNOR parameters: standard deviation (SD) of average AgNOR area and of AgNOR
      number, respectively. No correlation was found between AgNORs and the axillary
      nodal status (pN). The prognostic significance of AgNORs was estimated by using
      Cox regression analysis. In a multivariate approach offering all parameters
      available one AgNOR feature (coefficient of variation of relative AgNOR area)
      ranked at the third position beyond the SD of DNA distribution and the pTNM
      staging. Considering the distant-recurrence free interval of patients instead of
      the survival time the same AgNOR feature showed an independent prognostic value.

PMID- 7515675
TI  - [Demonstration and possible prognostic value of the nucleolar organizer region
      (NOR), the microtubule-associated proteins 1A/1B (MAP) and the intermediate
      filaments vimentin and cytokeratin 19 in invasive ductal breast carcinoma].
AB  - We examined the expression of the nucleolar organizer region, the microtubule
      associated protein and the intermediate filaments vimentin and cytokeratin 19 and
      their possible value for prognosis in 51 infiltrating ductal breast carcinomas.
      We registered the highest NOR counts in pT2/3-tumors, in poorly differentiated
      breast carcinomas, in tumors with a strong MAP- and vimentin expression (this
      holds true for vimentin only in pT2/3-tumors). There was a relationship between
      areas of NOR and the differentiation degree on the one hand and the MAP- and
      vimentin expression on the other hand. The area of nucleolus increased with the
      decrease of differentiation and with the increase of vimentin expression,
      respectively. The expression of cytokeratin 19 showed no homogeneous relations to
      the traditional prognostic factors as well as to the parameters of the NOR. The
      area of nucleus had no prognostic value in our study. The value of the NOR is
      limited by its high variation. The NORs are suitable only as an adjuvant factor
      for the prognosis. Further studies into MAP and vimentin and their role in the
      prognosis of infiltrating ductal breast carcinomas appear to be important.

PMID- 7515671
TI  - Sequential quantification of AgNOR area and number during silver staining by
      means of an image analysing system.
AB  - Standardized AgNOR staining protocols are required to compare results obtained by
      means of image analysis systems (IAS) in different laboratories. In order to
      investigate the staining kinetics of the NOR silver staining, we evaluated
      automatically the area and number of AgNORs of a human transitional-cell
      carcinoma cell line (HOK-1) by IAS at one minute intervals over a total staining
      period of 30 minutes. Results showed a constant increase (standard error of
      estimate: 0.001; R squared: 0.8) of the AgNOR area reaching a plateau after 10
      minutes followed by further area increase. In contrast, in all experiments a
      pronounced variability in the AgNOR number (standard error of estimate: 0.042; R
      squared: 0.75) was noted, reflecting the aggregation of silver stained spots.
      Thus the evaluation of the AgNOR area yielded reliable and easily reproducible
      results, whereas the assessment of the AgNOR number by means of an automated IAS
      was associated with a marked variability.

PMID- 7515676
TI  - AgNOR proteins as a parameter of the rapidity of cell proliferation.
AB  - A series of studies on the relationship between AgNOR quantity and cell kinetics
      have been reviewed. The results indicate that the quantity of interphase AgNORs,
      evaluated by morphometric analysis, increases in cycling cells from early G1
      phase to the late S-phase. In cancer tissues the AgNOR value is also closely
      related to both the percentage of cycling cells (measured by Ki67 or PCNA
      immunolabelling) and S-phase cells (measured by BrdU incorporation or DNA flow
      cytometry). Data from cell lines cultured in vitro have clearly shown that
      interphase AgNOR quantity is related to cell doubling time: the faster the
      rapidity of cell proliferation, the greater the interphase AgNOR quantity.

PMID- 7515677
TI  - Nucleolar organizer regions (AgNORs) in primary and recurrent gliomas. A
      retrospective study.
AB  - To assess the diagnostic and prognostic relevance of nucleolar organizer regions
      (AgNORs) the silver-stained AgNOR structures of 46 human gliomas (22 primary
      gliomas, 21 first and 3 second recurrences) from 28 patients were counted and
      measured. Surgical specimens of two neuropathological centres were included in
      this retrospective study. The tumours were classified into 8 groups according to
      WHO criteria of diagnosis and grading and their state of recurrence: 1: primary
      glioma grade II; 2: primary glioma grade III; 3: glioblastoma grade IV; 4: first
      recurrence of glioma grade II; 5: first recurrence of glioma grade III; 6: first
      recurrence of glioblastoma grade IV; 7: second recurrence of glioma grade II and
      8: second recurrence of glioma grade III. AgNOR numbers demonstrated a positive
      correlation with increasing histological grade. Similarly, higher levels of
      AgNORs were in general found in recurrent tumours compared to primary tumours
      with few exceptions in groups, in which few numbers only could be analyzed. The
      present study demonstrates the utility of evaluating AgNOR in assessing malignant
      gliomas and indicates that recurrences have a higher proliferative potential than
      original tumours. The problems of standardization of the AgNOR technique are
      especially crucial for the retrospective evaluation of fixed and embedded
      pathological material.

PMID- 7515678
TI  - AgNOR- and PCNA-studies in astrocytomas of the optic nerve.
AB  - Nine pilocytic astrocytomas of the optic nerve were investigated with the AgNOR
      method and by immunohistochemistry with anti-PCNA antibodies. Four patients were
      male, 5 female (mean age 16.5 years, range 1-55 years). Seven pilocytic
      astrocytomas were low-grade tumors (grade I, WHO [2]), one tumor contained giant
      cells and prominent nuclei (grade II), the remaining tumor was anaplastic (grade
      III). In each case, 5 randomly chosen areas were investigated by light microscopy
      using objective 40. The PCNA staining index was defined as number of positive
      tumor cell nuclei divided by the total amount of tumor cell nuclei in the
      microscopic field. Tumors showing only one immunopositive cell nucleus at low
      magnification were considered to have a staining index below 0.1%. The staining
      index of the 7 grade I tumors was below 0,1%, the grade II tumor showed a
      staining index of 1%, and the anaplastic astrocytoma (grade III) demonstrated a
      2.5% staining index. Investigations with the AgNOR method confirmed the above
      results of a low growth fraction in grade I-III grade astrocytomas of the optic
      nerve. Though low growth fractions have been reported in anaplastic astrocytomas
      and glioblastomas of the cerebrum, the low staining index in the anaplastic
      pilocytic astrocytoma of our series is remarkable: Instead of histological
      parameters like cellular and nuclear polymorphism and cellular density, the
      growth fraction could be a better parameter for the clinical course, which has in
      fact been benign in this case of an anaplastic pilocytic astrocytoma of the optic
      nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515679
TI  - Nucleolar organizer regions (AgNORs) in astrocytic tumors.
AB  - 79 astrocytic tumors classified according to the WHO classification and stained
      with a modified AgNOR staining technique were analysed with the help of an
      automatic image analysing system. The number and area of AgNORs were determined.
      The mean AgNOR number per nucleus was 1.28 in pilocytic, 1.98 in differentiated,
      2.84 in anaplastic astrocytomas, 3.33 in small cell glioblastomas and 4.24 in
      multiforme glioblastomas. The area of all AgNORs per cell ranged from 0.95
      microns2 (pilocytic astrocytomas), 1.53 microns2 (differentiated astrocytomas),
      2.73 microns2 (anaplastic astrocytomas), 3.1 microns2 (small cell glioblastomas)
      to 4.12 microns2 (multiforme glioblastomas). With regard to AgNORs there are
      little differences between anaplastic astrocytomas and small cell glioblastomas.

PMID- 7515680
TI  - [Use of the AgNOR method for the differential diagnosis of tumors and for the
      quantification of non-neoplastic epidermal hyperproliferation in
      dermatohistology].
AB  - The AgNOR number (NN) and the AgNOR quotient (NQ) of 228 melanocytic, epidermal
      and fibrohistiocytic lesions were investigated by image analysis. In melanocytic
      nevi, dysplastic nevi and Spitz nevi, significantly less AgNORs were seen than in
      malignant melanomas and melanomas in situ. Significant differences in AgNOR
      expression were detected between the subtypes of melanoma, too. Epidermal
      carcinomas showed a significantly higher AgNOR expression than keratoacanthomas
      and other benign tumors. Between the G1 carcinomas and the G2 and G3 groups, an
      increase of the NN and NQ was found. Actinic keratosis demonstrated a
      significantly lower AgNOR expression than carcinomas and--like M. Bowen--higher
      NN and NQ than the benign lesions. The lowest AgNOR results of fibrohistiocytic
      lesions were registered in regressive palmar fibromatosis and in scars, the
      highest in malignant fibrous histiocytomas. Between dermato-fibrosarcoma
      protuberans, atypical fibroxanthoma and malignant fibrous histiocytomas,
      significant differences were found to exist. Furthermore we examined the
      suitability of the AgNOR technique for quantification of epidermal cell kinetics
      in non-neoplastic epidermal hyperproliferations. Especially in the grading of
      psoriasis this technique is helpful. First convincing results could be achieved
      for the use of the AgNOR method in the verification of antiproliferative effects
      of new substances in an experimental mouse tail test. This study demonstrated
      that the AgNOR technique in addition to the dermatohistological differential
      diagnosis of tumors is useful for the quantification of antiproliferative effects
      of different treatments in hyperproliferative epidermal dermatosis.

PMID- 7515681
TI  - On the mechanism of action of cytochrome P450: evaluation of hydrogen abstraction
      in oxygen-dependent alcohol oxidation.
AB  - The mechanisms of oxidation of primary and secondary benzylic alcohols to the
      corresponding carbonyl compounds by purified rabbit liver cytochrome P450 forms
      2B4 and 2E1 in a reconstituted enzyme system has been examined by linear free
      energy relationships, intramolecular and steady-state deuterium isotope effects,
      and the incorporation of an O2-derived oxygen atom or solvent-derived deuterium.
      The kcat and Km values were found to be relatively insensitive to the presence of
      electronic perturbations at the para position. The Hammett reaction constants for
      the oxidation of benzyl alcohols by P450s 2B4 and 2E1 are -0.46 and -0.37,
      respectively, and with 1-phenylethyl alcohols the corresponding reaction
      constants are -1.41 and -1.19, respectively. With [1-2H1]benzyl alcohol, P450s
      2B4 and 2E1 show similar intramolecular deuterium isotope effects of 2.6 and 2.8,
      respectively, whereas with [1-2H2]benzyl alcohol under steady-state conditions,
      the deuterium isotope effects on the catalytic constants are 2.8 and 1.3,
      respectively. No significant isotope effect on the catalytic constant was noted
      for either form of P450 with 1-phenylethyl alcohol. In D2O, acetophenone formed
      by either form of P450 from 1-phenylethyl alcohol does not contain a deuterium
      atom at the methyl group, whereas under an atmosphere of 18O2 approximately 30%
      of the labeled oxygen is incorporated into the carbonyl group with either form of
      the cytochrome. The results are consistent with a mechanism that involves
      stepwise oxidation of the alcohol to a carbon radical alpha to the alcohol
      function, followed by oxygen rebound to yield the gem-diol, dehydration of which
      gives the carbonyl product.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515683
TI  - Folding of insulin-like growth factor I is thermodynamically controlled by
      insulin-like growth factor binding protein.
AB  - Insulin-like growth factor I (IGF-I) is thermodynamically unable to
      quantitatively form its native disulfides under reversible redox conditions in
      vitro [Hober et al. (1992) Biochemistry 31, 1749-1756]. These results prompted
      the question of how IGF-I may overcome this energetic problem in its folding in
      vivo. Here, we report that an IGF-I precursor, IGF-I-Ea, shows disulfide-exchange
      folding properties similar to those of mature IGF-I and, thus, is concluded not
      to overcome the identified folding problem of mature IGF-I. However, correct
      disulfide bonds are formed very efficiently when insulin-like growth factor
      binding protein 1 is added in equimolar amounts to IGF-I to the refolding
      mixture. On the basis of these results, we propose that one important function of
      at least one of the six homologous insulin-like growth factor binding proteins is
      to assist in the formation and maintenance of the native disulfides of IGF-I. To
      our knowledge, this is the first example where the folding of a mammalian protein
      or peptide in circulation has been demonstrated to be thermodynamically
      controlled by its binding protein. Speculatively, this could provide a mechanism
      to regulate the half-life of IGF-I in vivo by altering the interaction with
      insulin-like growth factor binding proteins.

PMID- 7515684
TI  - Conformation states of gramicidin A along the pathway to the formation of
      channels in model membranes determined by 2D NMR and circular dichroism
      spectroscopy.
AB  - Gramicidin A incorporated into SDS (sodium dodecyl sulfate) micelles exists as a
      right-handed, N-to-N-terminal beta 6.3 helical dimer [Lomize, A. L., Orechov, V.
      Yu., & Arseniev, A.S. (1992) Bioorg. Khim. 18, 182-189]. In the incorporation
      procedure to achieve the ion channel state of gramicidin A in SDS micelles,
      trifluoroethanol (TFE) is used to solubilize the hydrophobic peptide before
      addition to the aqueous/micelle solution. The conformational transition of
      gramicidin A to form ion channels in SDS micelles, i.e., in TFE and 10%
      TFE/water, has been investigated using 2D NMR and CD spectroscopy. In neat TFE,
      gramicidin A was found to be monomeric and may possibly exist in an equilibrium
      of rapidly interconverting conformers of at least three different forms believed
      to be left- and/or right-handed alpha and beta 4.4 helices. It was found that the
      interconversion between these conformers was slowed down in 55% TFE as evident by
      the observation of at least three different sets of d alpha N COSY peaks although
      CD gave a net spectrum similar to that in neat TFE. In 10% TFE gramicidin A
      spontaneously forms a precipitate. The precipitated species were isolated and
      solubilized in dioxane where gramicidin conformers undergo very slow
      interconversion and could be characterized by NMR. At least seven different
      gramicidin A conformations were found in 10% TFE. Four of thes are the same types
      of double helices as previously found in ethanol (i.e., a symmetric left-handed
      parallel beta 5.6 double helix, an unsymmetric left-handed parallel beta 5.6
      double helix, a symmetric left-handed antiparallel beta 5.6 double helix, a
      symmetric right-handed parallel beta 5.6 double helix); the fifth is possibly a
      symmetric right-handed antiparallel beta 5.6 double helix. There is also evidence
      for the presence of at least one form of monomeric species. Previous observation
      on the solvent history dependence in the ease of channel incorporation may be
      explained by the presence of several different folding pathways to channel
      formation. To test this proposal, the conformation of gramicidin A in 10% DMSO
      and 10% methanol was studied. In the former environment, the major form was a
      random coil with a minor population of double-stranded helices, while in the
      latter, NMR spectra indicate the presence of the same double-helical conformers
      as found in neat methanol.

PMID- 7515682
TI  - Nonhydrolyzable phosphotyrosyl mimetics for the preparation of phosphatase
      resistant SH2 domain inhibitors.
AB  - Src homology 2 (SH2) domains participate in protein tyrosine kinase (PTK)
      mediated cellular signal transduction through their ability to bind with high
      affinity to phosphotyrosyl (pTyr)-bearing protein sequences. Although peptides
      containing pTyr competitively inhibit the binding between phosphoproteins and
      cognate SH2 proteins in a sequence-specific manner, such peptides are rapidly
      dephosphorylated by cellular phosphatases. We now describe our efforts to develop
      SH2 inhibitory peptides containing phosphatase-resistant pTyr surrogates. The
      parent compound, (phosphonomethyl)phenylalanine (Pmp), is a phosphonate-based
      mimetic of pTyr in which the phosphate ester oxygen (> COPO3H2) has been replaced
      by a methylene unit (> CCX2PO3H2, X2 = H2). Pmp analogues bearing fluorine (X2 =
      H, F or X2 = F2) or hydroxyl (X2 = H, OH) substituents on the phosphonate alpha
      methylene carbon have been prepared and incorporated into peptides for use as SH2
      domain inhibitors. In an assay using the C-terminal SH2 domain of
      phosphatidylinositol (PI) 3-kinase, peptides having a GXVPML sequence [where X =
      pTyr, Pmp, hydroxy-Pmp (HPmp), monofluoro-Pmp (FPmp), and difluoro-Pmp (F2Pmp)]
      exhibited binding potency in the order HPmp < Pmp < FPmp < F2Pmp = pTyr. Distinct
      peptide sequences which bind selectively with Src and Grb2 SH2 domains were also
      prepared with pTyr and F2Pmp. The F2Pmp peptides bound with high (0.2- to 5-fold)
      relative affinity, compared to analogous pTyr peptides. We conclude that peptides
      containing F2Pmp bind to SH2 domains with high affinity and specificity and,
      being resistant to cellular phosphatases, should provide a generally useful tool
      for disrupting SH2 domain-mediated signaling pathways in intact cells.

PMID- 7515685
TI  - Alamethicin pyromellitate: an ion-activated channel-forming peptide.
AB  - The synthesis and characterization of alamethicin pyromellitate (Alm-PM), a
      derivative of the channel-forming peptide alamethicin bearing three negative
      charges at the C-terminus, is described. The self-association of Alm-PM in small
      unilamellar vesicles of dioleoylphosphatidylcholine (DOPC), monitored using
      circular dichroism (CD) spectroscopy, occurs much less readily than the self
      association of unmodified alamethicin. Channel formation by Alm-PM also occurs
      less readily and exhibits a higher voltage threshold for activation in planar
      lipid bilayers and in lipid vesicles. An increase in the salt concentration, and
      particularly the addition of calcium ions, promotes Alm-PM self-association as
      monitored by CD spectroscopy. Calcium also facilitates channel formation by Alm
      PM both in planar lipid bilayers and in lipid vesicles by lowering the voltage
      threshold for activation. Thus Alm-PM behaves as an ion-activated ion channel.
      These results indicate that the self-association of alamethicin-like peptides in
      membranes is critical for channel formation and that transmembrane flip-flop of
      peptide helices is not required. In addition, these results demonstrate that the
      activity of channel-forming peptides may be controlled by controlling the process
      of self-association.

PMID- 7515687
TI  - Unique epitope of apolipoprotein A-I expressed in pre-beta-1 high-density
      lipoprotein and its role in the catalyzed efflux of cellular cholesterol.
AB  - The ability of mouse anti-apolipoprotein A-I (apo A-I) monoclonal antibodies to
      recognize pre-beta-HDL species in native plasma was determined. An antibody
      identifying residues 137-144 of the mature protein uniquely recognized pre-beta-1
      HDL, an HDL species of low molecular weight implicated in early cholesterol
      transport from cell membranes to plasma [Castro, G. R., & Fielding, C. J. (1988)
      Biochemistry 27, 25-29]. Incubation of plasma with this antibody significantly
      inhibited the efflux of labeled cholesterol from cultured fibroblast monolayers.
      A second antibody, binding to residues 93-99 of apo A-I, recognized a second pre
      beta-HDL species (pre-beta-2 HDL) but not pre-beta-1 HDL and did not inhibit
      cholesterol efflux. Several other antibodies had broad specificity for HDL
      (including pre-beta-1 HDL). This research suggests that apo A-I residues 137-144
      are adjacent to or part of a structural site in pre-beta-1 HDL active in
      promoting the efflux of cellular cholesterol and that this site is not exposed in
      other HDL species.

PMID- 7515688
TI  - Sequence and functional expression of an amphibian water channel, FA-CHIP: a new
      member of the MIP family.
AB  - A new member of the family of water channel proteins (aquaporin-CHIP) related to
      the major intrinsic protein (MIP) family is described. The cDNA coding for this
      amphibian CHIP was cloned from frog (Rana esculenta) urinary bladder, a model for
      the kidney collecting duct, using a RT-PCR cloning strategy. The encoded protein,
      designated FA-CHIP (frog aquaporin-CHIP), shows 77.4%, 42.4% and 35.6% identity
      with the three proteins now referred to as the aquaporins of the MIP family,
      i.e., human CHIP28, WCH-CD and gamma-TIP, respectively. Xenopus leavis injected
      with FA-CHIP cRNA exhibited a marked increase of the osmotic water permeability.

PMID- 7515689
TI  - Steady state levels of mitochondrial and nuclear oxidative phosphorylation
      transcripts in Kearns-Sayre syndrome.
AB  - The steady state levels of both mitochondrial and nuclear transcripts were
      examined in a Kearns-Sayre syndrome patient harboring a heteroplasmic 7.7 kb
      mitochondrial DNA deletion. Transcripts originating from the genes located
      outside of the deletion were present in similar amounts to those of control
      samples, with the transcript levels of each tissue linked to its oxidative
      phosphorylation capacities. Transcripts originating from genes within the
      deletion were reduced according to the percentage of mtDNA deleted molecules in
      the tissue. The fusion transcript resulting from the rearranged genome is
      expressed in all the tissues tested and its level is related to the amount of the
      deleted mtDNA. The RNA levels from three nuclear genes encoding two of the
      Adenine Nucleotide Translocator isoforms (ANT1 and 2) and the beta subunit of the
      ATPsynthase (ATPsyn beta) were significantly induced in the different tissues
      independently of the percentage of deleted mtDNA molecules. In contrast, the ANT1
      and ATPsyn beta levels were decreased in skeletal muscle. This result could be
      related to the different distribution of the deleted molecules in tissues.

PMID- 7515686
TI  - Divergent structure of the human synexin (annexin VII) gene and assignment to
      chromosome 10.
AB  - The human synexin (annexin VII) gene occurs as a single copy at chromosome
      10q21.1-21.2 and substantially deviates in size and in the location of splice
      junctions from the other two well-characterized members of the annexin gene
      family, lipocortin I (annexin I) and calpactin I (annexin II). The synexin gene
      contains 14 exons, including an alternatively spliced cassette exon, and spans
      approximately 34 kb of DNA. Only five of the fourteen splice junctions are
      conserved compared to other annexins, and the differences are particularly
      pronounced in the exons that encode the C-terminal third and fourth conserved
      repeats in the gene product. Although parallels between exons and protein domains
      were not apparent, we did observe clustering of splice junctions corresponding to
      either the unique N-terminal domain or the conserved C-terminal tetrad repeat
      domain, which is common to all annexins. Furthermore, a complete analysis of the
      5' flanking region of the annexin VII gene revealed an entirely different set of
      cis-acting and enhancer elements compared to other annexin genes. We conclude
      that the annexin VII gene may have arisen by a divergence from the evolutionary
      pathway taken by both annexins I and II.

PMID- 7515691
TI  - Cancer biology.

PMID- 7515690
TI  - N omega -monomethyl-L-arginine inhibits nitric oxide production in murine cardiac
      allografts but does not affect graft rejection.
AB  - Endogenous nitric oxide biosynthesis in mice receiving allogeneic heterotopic
      heart transplants was monitored as a function of time post-transplant. Nitric
      oxide production was measured by daily urine nitrate levels and by formation of
      paramagnetic heme-nitrosyl complexes in the cardiac tissue. Exogenous sources of
      urine nitrate and EPR signal were minimized by maintaining the animals on a low
      nitrite/nitrate diet. Urine nitrate peaked on postoperative day 7. A heme
      nitrosyl EPR signal also appeared in the cardiac tissue on postoperative day 7
      and remained unchanged in size until rejection on postoperative day 9 at which
      time the peak height of the signal nearly tripled. Some of the animals in the
      study were treated with the nitric oxide synthase inhibitor, N omega-monomethyl-L
      arginine which caused marked inhibition of urinary nitrate excretion and
      prevented heme-nitrosyl complex formation in beating hearts. However,
      administration of the inhibitor did not increase graft survival time. Low
      intensity heme-nitrosyl signals were identified in inhibitor-treated allogeneic
      hearts after rejection. Syngeneic heart transplants did not induce urinary
      nitrate excretion nor EPR signal formation. These results show that cytokine
      induced high output nitric oxide synthesis from L-arginine is a prominent
      biochemical component of the cell-mediated immune response to cardiac allografts
      in mice. However, nitric oxide production was not essential for rejection of
      cardiac allografts mismatched at the major histocompatibility locus.

PMID- 7515692
TI  - Molecular mediators of interactions with extracellular matrix components in
      metastasis and angiogenesis.
AB  - Metastasis and tumor angiogenesis are invasive phenomena and share many common
      properties at the physiological level and some similarities at the molecular
      level. Each consists of repetitive cycles of interaction with adjacent
      extracellular matrix components by mediating cellular adhesion, matrix
      dissolution, and cellular motility to achieve metastasis of cancer cells or
      neovascularization of tumors. Molecular factors which implement this triad of
      events are reviewed, as are several signal transduction components which may
      regulate them. Some potentially promising prognostic, diagnostic, and therapeutic
      modalities for tumor angiogenesis and metastatic disease are also discussed.

PMID- 7515693
TI  - Chronic myelogenous leukemia.
AB  - The Ph chromosome, the abnormality characteristic of chronic myelogenous
      leukemia, was discovered in 1963. However, the events responsible for the
      pathogenesis and transformation to accelerated and blastic phases are still
      unknown at the molecular level and are subjects of ongoing research. The positive
      outcome in a subset of patients with interferon therapy and the potential for
      cure with bone marrow transplantation have evoked controversy regarding the best
      approach for different groups of patients according to prognostic
      characteristics. At the same time, new therapies with promising results are being
      developed, both in the setting of chemotherapy and biologic therapy and in bone
      marrow transplantation. Homoharringtonine chemotherapy, the use of matched
      unrelated donors for bone marrow transplantation, and new modalities of purging
      for autologous bone marrow transplantation are some examples. Sensitive molecular
      techniques that allow for the detection of small numbers of bcr-abl-positive
      hematopoietic cells may provide new means of assessing the results of current and
      future therapies.

PMID- 7515694
TI  - Multiple myeloma.
AB  - The mortality associated with multiple myeloma is due to the progressive
      accumulation of a clonal population of plasma cells in the bone marrow. Tumor
      cells may also be found in the blood and other extramedullary sites, especially
      in the terminal stages of the disease. During disease progression, numerous
      effects lead to significant morbidity, including immunosuppression, increased
      bone turnover, anemia, and renal deterioration. For more than two decades it has
      been realized that chemotherapy and radiotherapy could provide effective
      temporary relief from the pain and suffering associated with this malignancy.
      Unfortunately, these benefits are usually short lived, and essentially all
      patients experience recurrent disease that is usually refractory to additional
      therapy.

PMID- 7515695
TI  - Lead and pollution--an overview.

PMID- 7515697
TI  - Expression of stratified squamous epithelia-type cytokeratin by canine mammary
      epithelial cells during tumorigenesis: type I (acidic) 57 kilodalton cytokeratin
      could be a molecular marker for malignant transformation of mammary epithelial
      cells.
AB  - Two monoclonal antibodies (MAbs) were established in 20 clones of MAbs generated
      against cytokeratin fraction extracted from canine squamous cell carcinoma to
      investigate the expression of intermediate filament proteins during
      tumorigenesis. These MAbs were confirmed to react with purified cytokeratin by
      ELISA. One monoclonal antibody, MAb32 reacted all layers of epidermis except the
      cornified layer and mammary myoepithelial cells but not any epithelial cells.
      Another antibody named MAb24 exclusively reacted the basal monolayer of
      epidermis, the stratum germinativum. Any positive reactions with MAb24 were not
      detected in normal mammary gland. From the analysis by two-dimensional gel
      electrophoresis followed by immunoblotting, it was revealed that MAb24
      recognizing cytokeratin subunit gave a molecular weight of 57 kilodalton and a
      isoelectric-pH value of pI5.1, indicating type I (acidic) cytokeratin. In
      intraductal papillomas developed in canine mammary glands, most tumor cells were
      positively stained with MAb32 in addition of myoepithelial cells while no
      positive reaction with MAb24 was seen. In ductal carcinomas, MAb24-positive
      cytokeratin was begun to express by tumor cells with positive reaction of MAb32
      where these cells showed infiltrative growth into the stroma. We therefore
      proposed that 57 kilodalton-type I cytokeratin was a molecular marker for
      malignant transformation in canine mammary tumor and these antibodies could be
      useful tools to investigate the change of cytokeratin expression during
      tumorigenesis.

PMID- 7515699
TI  - Confocal fluorescence microscopy of urokinase plasminogen activator receptor and
      cathepsin D in human MDA-MB-231 breast cancer cells migrating in reconstituted
      basement membrane.
AB  - Using confocal fluorescence microscopy with a monoclonal antibody, we have
      localized the receptor for urokinase plasminogen activator (uPAR) in MDA-MB-231
      human breast cancer cells migrating into a reconstituted basement membrane.
      Patchy and polarized uPAR immunoreactivity was found at the cell membrane, and
      strong staining was found both in the ruffled border or leading edge of the cells
      and at pseudopodia penetrating into the membrane. Intracellular uPAR staining was
      localized in the paranuclear region and in rounded granule-like structures; some
      of these were identified as lysosomes by double staining for uPAR and the
      lysosomal enzyme cathepsin D. Urokinase plasminogen activator (uPA) activity has
      previously been shown to play a role in migration of cells into basement
      membranes, and it has been proposed that uPAR also is involved in this process.
      uPA is known to be internalized and degraded after complex formation with the
      inhibitor PAI-1. Lysosomal uPAR immunoreactivity may result from concomitant
      internalization of the receptor.

PMID- 7515700
TI  - Staining and histomorphometry of microcracks in the human femoral head.
AB  - We developed staining techniques that permit identification and histomorphometric
      analysis of microcracks in the human femoral head 1) from thick, ground bone
      sections (100 microns) by prestaining with the Villanueva mineralized bone stain
      (MIBS), and 2) from plastic embedded, undecalcified thin bone sections (5-15
      microns) by staining in gallocyanin chrome alum-Villanueva blood stain methods.
      Both methods represent a significant improvement in the stainability of the
      microcracks, cellular and tissue elements, and the simultaneous assessment of
      osteoid seams and tetracycline markers by histomorphometry. Shrinkage and other
      artifacts were minimized, which helped to clarify some of the uncertainties
      arising from artifacts resulting from some bone staining methods.
      Histomorphometric analyses of microcracks were conducted on thick, ground
      sections of subchondral and trabecular bone. Microcracks were more prevalent in
      the subchondral bone and osteochondral junction than in the more distant
      trabeculae. We have consistently localized microcrack areas in bone tissues
      prepared in these ways.

PMID- 7515698
TI  - Phagocytosis of intravenously administered particles by leukocytes adhered to the
      aortic endothelium of the rat.
AB  - Phagocytosis has been used to characterize on a functional basis leukocytes
      adhered to the aortic endothelium of the rat. After intravenous administration of
      particles, phagocytosis was observed microscopically in esterase-positive
      leukocytes adhered to the endothelium in whole mounts of aorta. Polybead blue and
      red, 0.5 and 1 microns particle size, were inadequate because they were
      insufficiently colored to be identified individually at 400 x. Fluoresbrite YG
      0.25 and 0.50 micron at doses of 0.2 and 2 x 0.3 ml/100 g, respectively, produced
      endothelial lesions. The same occurred with Monastral blue B (MbB) at 0.3 ml/100
      g, red iron at 2 x 16 mg/100 g and India ink at different concentrations
      depending on the supplier. At lower particle doses, lesions were not found.
      Deferoxamine mesylate 1.5 mg/100 g intravenous and allopurinol 5 mg/100 g
      intraperitoneal administered before the particles diminished the number and
      intensity of lesions. In none of the cases studied was the percentage of
      phagocytic cells greater than 50%. Clearance curves of MbB and Fluoresbrite
      indicated rapid disappearance of particles from the blood. Results indicate that
      administration of particulate suspensions is not a good method for characterizing
      the phagocytic leukocytes adhering to the aortic endothelium because low doses
      produce rapid clearance of particles, thus impeding sufficient leukocyte loading,
      and higher doses produce endothelial lesions that often impair reliable counting
      of the adhering leukocytes.

PMID- 7515696
TI  - Identification of a bovine serum mannan-binding protein reactive with a Ra
      chemotype strain of Salmonella serovar typhimurium.
AB  - To study the relationship between a bovine serum mannan-binding protein (MBP) and
      a serum protein reactive with a Ra chemotype strain of Salmonella serovar
      Typhimurium (Ra-reactive factor, RaRF), both proteins were isolated by use of
      their affinity for yeast mannan and the Salmonella cells followed by affinity
      chromatography on mannobiose-Sepharose 4B. Both purified proteins showed a major
      protein band with a molecular weight of 33,000 and a few faint bands in sodium
      dodecyl sulfate-polyacrylamide slab gel electrophoresis under reducing
      conditions. In Western blotting with rabbit anti-bovine MBP antibody, the major
      subunit of both proteins were found to be immunologically identical. Similar
      findings were also obtained with purified human MBP and RaRF. From these
      findings, bovine and human serum MBP are suggested to be electrophoretically and
      immunologically the same as their corresponding RaRF.

PMID- 7515701
TI  - Disease due to the Mycobacterium avium complex in patients infected with human
      immunodeficiency virus: diagnosis and susceptibility testing.
AB  - Because the symptoms and laboratory abnormalities associated with disseminated
      disease due to the Mycobacterium avium complex (MAC) are nonspecific, diagnosis
      requires recovery of the organism from blood or other normally sterile body
      sites. Isolation of MAC by conventional mycobacterial culture on tubed solid
      medium generally takes 3-4 weeks. This interval can be decreased to 5-12 days
      with the radiometric BACTEC TB system and to 12-19 days with Septi-Chek AFB. For
      diagnosis of MAC bacteremia, blood is inoculated directly into a BACTEC TB 13A
      blood culture vial. For quantitative cultures, blood is collected in an Isolator
      lysis-centrifugation tube, and the sediment of the processed sample is inoculated
      onto agar plates. MAC is identified by conventional biochemical tests, which take
      several weeks or months, or with commercial DNA probes or chromatography, each of
      which provides results in a few hours. No standardized reference method for
      antimicrobial susceptibility testing exists, and no correlation between in vitro
      results and clinical efficacy is clear. Isolates appear more sensitive in broth
      than on agar. Evaluation of susceptibility in macrophage and animal models is
      helpful because drugs concentrated in cells may be more efficacious against MAC-
      an intracellular pathogen--than would be predicted by results in cell-free
      systems.

PMID- 7515703
TI  - Intraoperative coronary thrombosis: can protamine be incriminated?

PMID- 7515705
TI  - Autologous blood donation before myocardial revascularization: a Holter
      electrocardiographic analysis.
AB  - The influence of preoperative autologous blood donation on myocardial ischemia
      and arrhythmias was evaluated in 24 patients scheduled for coronary artery bypass
      grafting (CABG). All had a Holter recorder placed 24 hours before predonation
      (day 1), the cassette was changed prior to donation, and the recording continued
      for 24 hours thereafter (day 2). Each patient served as his or her own control,
      and observations made on day 2 were compared with those of day 1. Ischemia was
      quantitated by calculating the duration (C.Dur.) and the area (C. Area) of
      ischemic ST segment depressions, and ventricular premature beats (VPB) were
      classified according to the Lown grading system. Twenty-one men and 3 women were
      monitored. On day 1, 9 patients had 20 ischemic events, 3 being symptomatic. Nine
      patients demonstrated ischemia on day 2, representing a total of 3 symptomatic
      and 26 silent events. When comparing the two monitoring periods, 7 patients had
      longer or more severe ST segment depression whereas 6 other patients presented
      with more severe VPBs on day 2. Three patients had less ischemia on day 2, one
      remained stable, and 13 had no ischemia throughout the study. Silent ischemia was
      significantly more prolonged (C.Dur.Sil 316 v 152 sec, P < 0.05) and more intense
      (C. Area Sil 8 v 3.8 mm.min, P < 0.05) on day 2. Moreover, on top of a normal
      circadian distribution of ischemic events in the morning and in the evening, 40%
      of events were related to the donation or to a trip to the hospital. No
      preoperative characteristic helped to detect patients at risk.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7515702
TI  - Intraoperative coronary thrombosis: can aprotinin be incriminated?

PMID- 7515706
TI  - Magnesium and arrhythmias after coronary artery bypass surgery.
AB  - Arrhythmias are very common after cardiac surgery and are multifactorial.
      Magnesium is receiving increased consideration in the management of
      supraventricular and ventricular arrhythmias. This study was designed to evaluate
      the role of magnesium in preventing arrhythmias in hypokalemic (K < 3.5 mEq/L)
      and normokalemic (K > 3.5 mEq/L) patients with normal renal and ventricular
      function after coronary artery bypass grafting (CABG). One hundred forty patients
      ranging from 32 to 71 years of age who were scheduled for CABG were studied. They
      were divided into four groups: group I (control) received no magnesium; group II
      received 10 mg/kg of magnesium sulfate intravenously before cardiopulmonary
      bypass (CPB); group III received 10 mg/kg of magnesium soon after CPB; group IV
      received 10 mg/kg of magnesium before and after CPB. Serum potassium and
      catecholamine levels, as well as serum and urine magnesium levels, were measured
      and the incidence and type of arrhythmias were determined. There was a
      statistically significant difference in the occurrence of arrhythmias between the
      groups studied. The incidence of arrhythmias was highest in groups I and II and
      lowest in group IV (12 patients in group I, 14 in group II, 5 in group III; and 1
      in group IV). Magnesium levels were higher in group IV than any other group
      studied after completion of surgery. There was no difference in serum and urine
      magnesium levels between the hypokalemic and normokalemic patients within each
      group. Serum magnesium returned to normal in all patients after 48 hours.
      Therefore, it appears that administration of magnesium during and after cardiac
      surgery reduces the incidence of arrhythmias in hypokalemic and normokalemic
      patients.

PMID- 7515704
TI  - Alternative perioperative anticoagulation monitoring during cardiopulmonary
      bypass in aprotinin-treated patients.
AB  - Monitoring of anticoagulation during cardiopulmonary bypass by means of the
      activated coagulation time (ACT) has become questionable due to the prolongation
      in the clotting time of patients receiving aprotinin. Because the celite-based
      ACT only indicates intrinsic coagulation, and sufficient anticoagulation is
      needed to also prevent extrinsic coagulation, the ACT may not be reliable. Three
      different clotting times, the celite-based ACT, the kaolin-based activated
      coagulation time (AKT) and the high-dose thrombin time (HITT), were compared in a
      prospective, double-blind, placebo-controlled study of 20 patients who were to
      undergo cardiopulmonary bypass. As expected, neither the kaolin-based assay nor
      the high-dose thrombin time was influenced by aprotinin, whereas the celite-based
      ACT was significantly prolonged in aprotinin-treated patients as compared to
      control patients (P < 0.05). This study confirms that both kaolin-based and
      thrombin-based tests provide a reliable means of determining the degree of
      heparinization in the presence of aprotinin during cardiopulmonary bypass.

PMID- 7515707
TI  - Intraoperative coronary thrombosis: can aprotinin and protamine be incriminated?

PMID- 7515709
TI  - Anesthetic considerations for valve replacement surgery in a patient with
      carcinoid syndrome.

PMID- 7515708
TI  - Electrocardiographic ST segment changes associated with aprotinin and reversed
      with heparin in two patients having coronary artery reoperations.

PMID- 7515710
TI  - [Increase in nitric oxide generation in animal tissues during adaptation to short
      term stressor exposure (EPR study)].

PMID- 7515711
TI  - [Various components of the serotonin system in depressive disorders in
      psychopathic personalities].

PMID- 7515712
TI  - Association of p72 tyrosine kinase with Stat factors and its activation by
      interleukin-3, interleukin-6, and granulocyte colony-stimulating factor.
AB  - Hematopoietic cytokines, including interleukin-3 (IL-3), IL-6, and granulocyte
      colony-stimulating factor (G-CSF), induce the proliferation, differentiation, and
      activation of hematopoietic lineage cells. These cytokines activate the Jak/Stat
      mediated signal transduction pathway that is important in the biologic activities
      of these cytokines. In this study, we showed that hematopoietic cytokines, such
      as IL-3, IL-6, and G-CSF, all induced tyrosine-phosphorylation of Stat family
      proteins and Stat-associated 150-kD and 72-kD molecules in hematopoietic lineage
      cell lines. Furthermore, we showed that the 72-kD molecule had tyrosine kinase
      activity. The tyrosine kinase activity of the 72-kD molecule was enhanced by the
      stimulation through an IL-6 signal transducer, gp130, that was shared among the
      receptors for the IL-6-related cytokine subfamily, such as leukemia inhibitory
      factor, oncostatin M, IL-11, and ciliary neurotrophic factor. Because 72-kD
      tyrosine kinase was distinct from Syk, Tec, and Btk and coimmunoprecipitated with
      anti-Stat antiserum, we termed it Stat-associated 72-kD tyrosine kinase (p72sak).
      p72sak may directly activate Stat family proteins or other signal transducing
      molecules for IL-3, G-CSF, and the IL-6-related cytokine subfamily.

PMID- 7515713
TI  - Demonstration that Thy(lo) subsets of mouse bone marrow that express high levels
      of lineage markers are not significant hematopoietic progenitors.
AB  - We have been unable to reproduce experiments suggesting the existence of three
      lineage-restricted progenitor populations from mouse bone marrow. Thy1.1loMac
      1+B220+ cells were reported to give rise to greatly expanded numbers of myeloid
      and lymphoid cells, while Thy1.1loMac-1+B220- and Thy1.1loMac-1-B220+ cells were
      reported to be highly proliferative myeloid and B-lineage-restricted progenitors,
      respectively. Both Mac-1+ cell types appear to be much less frequent than
      previously reported, and we observed no activity consistent with their
      characterization as committed progenitors of expanded numbers of cells. The
      original identification of these populations may have resulted from a failure to
      distinguish bonafide signals from autofluorescent background and nonspecific
      staining. The progenitor activities originally associated with these populations
      may have been due to hematopoietic stem cell contamination. This study shows that
      low levels of Mac-1 are expressed on cells with multipotent progenitor activity.
      Thy1.1loB220+Mac-1- cells can be purified from bone marrow, but in these
      experiments they do not give rise to detectable levels of progeny on injection
      into lethally irradiated mice. Thy1.1loB220+Mac-1- cells appear to be pro-B cells
      without significant proliferation potential in vivo. The finding that the
      described populations do not have the reported progenitor activities leaves the
      pathways of stem cell differentiation open to further study.

PMID- 7515714
TI  - Total marrow failure induced by pegylated stem-cell factor administered before 5
      fluorouracil.
AB  - To examine the potential role of stem-cell factor (SCF) in cancer chemotherapy,
      we have administered it to mice either before or after 5-fluorouracil (5-FU).
      When polyethylene glycolated (PEG-ylated) SCF was administered to mice before 5
      FU, it had a significant sensitizing effect on primitive bone marrow cells.
      Examination of the hematopoietic status of these mice showed that the damage
      caused by 5-FU to both bone marrow and spleen hematopoiesis was exaggerated when
      it was preceded by SCF. SCF given before each of two 5-FU treatments at 7-day
      intervals resulted in the death of all treated mice. The time of death and
      hematopoietic status of these animals are compatible with the onset of
      hypoplastic marrow failure leading to pancytopenia and death. SCF given after 5
      FU had little impact either on the initial degree of hematopoietic damage or
      subsequent recovery. Gut populations were similarly sensitized to 5-FU by prior
      treatment with SCF, and the damage caused to intestinal populations was greater
      than that resulting from 5-FU alone. This indicates that the different tissues
      may be similarly sensitized by SCF. The sensitizing effect of SCF was reversed by
      concurrent administration of transforming growth factor (TGF)-beta 3, and
      survival of the majority of the mice was ensured. Examination of hematopoiesis in
      mice treated concurrently with SCF and TGF-beta 3 showed that the degree of
      marrow and spleen damage had reverted to that caused by 5-FU alone. In further
      experiments, 100% survival and normal hematopoiesis could be attained by
      transplantation of 1 million syngeneic bone marrow cells 24 hours after 5-FU
      treatment following SCF sensitization. These data indicate that PEG-ylated SCF
      can sensitize normally resistant hematopoietic and gut stem cells to the effects
      of 5-FU. This sensitization resulted in effective eradication of hematopoiesis in
      SCF-pretreated/5-FU-treated animals and their subsequent death from marrow
      failure. These findings imply that SCF pretreatment may represent a novel method
      of increasing the effectiveness of conventional chemotherapy, making marrow
      ablation more effective without drug dose escalation and perhaps sensitizing some
      tumor cells to the effects of therapy.

PMID- 7515715
TI  - C-kit gene is expressed by skin mast cells in embryos but not in puppies of
      Wsh/Wsh mice: age-dependent abolishment of c-kit gene expression.
AB  - The Wsh is a mutant allele at the W (c-kit) locus of mice, but no significant
      abnormalities are found at the coding region of the Wsh allele. Since cultured
      mast cells derived from the spleen of Wsh/Wsh mice do not express messenger RNA
      (mRNA) of c-kit, we studied the interrelation between the number of mast cells
      and the magnitude of c-kit mRNA expression in the skin of Wsh/Wsh mice of various
      ages. The number of mast cells in the skin of Wsh/Wsh embryos of 18 days
      postcoitum (pc) was approximately 40% that of normal control (+/+) embryos, but
      the number of mast cells decreased exponentially after birth; the number dropped
      to 0.6% that of +/+ mice at day 150 after birth. A weak but apparent signal of c
      kit mRNA was detectable in the skin of 18-day pc Wsh/Wsh embryos by RNase
      protection assay but not in the skin of 5-day-old Wsh/Wsh mice. The number of c
      kit protein-containing cells was significantly greater in the skin of 18-day pc
      Wsh/Wsh embryos than in the skin of 5-day-old Wsh/Wsh mice. The abolishment of c
      kit mRNA expression appeared to be specific, because the expression of mast cell
      carboxypeptidase A mRNA but not of c-kit mRNA was detectable by in situ
      hybridization in skin mast cells of 5-day-old Wsh/Wsh mice. Taken together, the
      expression of c-kit mRNA was abolished first, then the content of c-kit protein
      dropped to undetectable levels, and then the disappearance of Wsh/Wsh mast cells
      themselves followed.

PMID- 7515716
TI  - Identification of molecular defects in a subject with type I CD36 deficiency.
AB  - We performed a molecular analysis of a subject whose platelets and monocytes did
      not express any cell surface CD36 (designated as a type I CD36 deficiency).
      Amplification of the 5' half of platelet and monocyte CD36cDNA (corresponding to
      nucleotide [nt] 191-1009 of the published CD36 cDNA sequence [Oquendo et al,
      Cell, 58:95, 1989]) showed that two different-sized CD36 cDNAs existed. One cDNA
      was of predicted normal size, whereas the other was about 150 bp smaller than
      that predicted for normal CD36 cDNA. Amplification of the 3' region of CD36 cDNA
      (nt 962-1714) in this subject showed only normal-sized CD36 cDNA. Cloning and nt
      sequence analysis of the cDNAs showed that the smaller sized CD36 cDNA had 161-bp
      deletion (from nt 331 to 491), and a dinucleotide deletion starting at nt
      position 539. The same dinucleotide deletion was also detected in the normal
      sized CD36 cDNA. Both deletions caused a frameshift leading to the appearance of
      a translation stop codon. RNA blot analysis and quantitative assay using the
      reverse transcription-polymerase chain reaction (RT-PCR) showed that the CD36
      transcripts in both platelets and monocytes were greatly reduced. Comparison of
      the determined cDNA sequences with the genomic DNA sequence for the human CD36
      gene showed that the dinucleotide deletion was located in exon 5, and that the
      161-bp deletion corresponded to a loss of exon 4. PCR-based analysis using
      genomic DNA showed that this subject was homozygous for the dinucleotide deletion
      in exon 5. Except for the dinucleotide deletion, we could not find any
      abnormalities around exon 3, 4, and 5 including the splice junctions. These
      results suggested that the deletions in CD36 mRNA were likely to be responsible
      for instability of the transcripts, and the dinucleotide deletion in exon 5 might
      affect the splicing of exon 4.

PMID- 7515717
TI  - Piecemeal degranulation of mast cells in the inflammatory eyelid lesions of
      interleukin-4 transgenic mice. Evidence of mast cell histamine release in vivo by
      diamine oxidase-gold enzyme-affinity ultrastructural cytochemistry.
AB  - We used light and electron microscopy to analyze the eyelid inflammation that
      develops in transgenic mice that overexpress interleukin-4 (IL-4; Tepper et al,
      Cell 62:457, 1990). Analysis of alkaline Giemsa-stained plastic sections examined
      by light microscopy (Dvorak et al, J Exp Med 132:558, 1970), as well as by
      routine transmission electron microscopy, indicated that the mast cells in the
      inflammatory eyelid lesions were undergoing piecemeal degranulation, a form of
      secretion in which the cells' cytoplasmic granules exhibit characteristic
      morphologic changes that are thought to be associated with the prolonged, vesicle
      mediated release of the granules' constituents. Moreover, by using a newly
      reported enzyme affinity-gold method, which stains histamine based on binding to
      diamine oxidase-gold (Dvorak et al, J Histochem Cytochem 41:787, 1993), we show
      that these activated mast cells had released much of their histamine content. The
      eyelid lesions also exhibited increased numbers of mast cells; interstitial
      fibrosis, particularly around cutaneous nerves and blood vessels; activated
      fibroblasts; focal axonal damage; venules with endothelial cells containing
      numerous vesiculo-vacuolar organelles; and infiltrates of neutrophils and
      eosinophils. Our findings illustrate that overexpression of the IL-4 gene in vivo
      can result in eyelid lesions associated with piecemeal degranulation of mast
      cells, as well as tissue fibrosis and a variety of other pathologic changes.
      These results also represent the first direct morphologic evidence for histamine
      secretion by mast cells in vivo.

PMID- 7515718
TI  - RANTES- and interleukin-8-induced responses in normal human eosinophils: effects
      of priming with interleukin-5.
AB  - We report that responses of normal human eosinophils toward the chemokines RANTES
      and interleukin-8 (IL-8) are modulated and upregulated by priming with IL-5. In a
      modified Boyden chamber assay, we studied migratory responses toward the members
      of the chemokine family RANTES, monocyte chemotactic protein-1 (MCP-1), and
      macrophage inflammatory protein-1 alpha (MIP-1 alpha) (C-C subfamily), and IL-8,
      platelet factor-4 (PF-4), and neutrophil-activating peptide-2 (NAP-2) (C-x-C
      subfamily). These chemokines were also studied in terms of actin polymerization
      and ([Ca2+]i)-mobilizing properties, intracellular signals that are thought to
      play a role during migratory responses. We found that eosinophils showed
      significant migratory responses toward RANTES and IL-8 at concentrations of 10(
      9) to 10(-7) mol/L only after priming with IL-5 (10 pmol/L). At these
      concentrations, PF-4, NAP-2, MCP-1, and MIP-1 alpha induced no significant
      migratory responses after priming. Unprimed eosinophils only showed a significant
      migratory response toward RANTES (10(-6) mol/L). Changes in [Ca2+]i were found
      after addition of RANTES, MIP-1 alpha, and NAP-2 (10 nmol/L) to unprimed
      eosinophils. RANTES (10(-9) to 10(-7) mol/L) significantly induced actin
      polymerization both in primed and unprimed eosinophils, whereas IL-8 (10(-9) to
      10(-8) mol/L) and MIP-1 alpha (10(-8) mol/L) only induced actin polymerization
      after priming with IL-5. NAP-2, PF-4, and MCP-1 did not affect actin
      polymerization. These findings are further evidence for the hypothesis that
      cytokines like IL-5 and locally secreted chemokines like RANTES and IL-8 are both
      at the basis of specific eosinophil influx into the allergic inflammatory locus.

PMID- 7515719
TI  - Increased expression of the G gamma and A gamma globin genes associated with a
      mutation in the A gamma enhancer.
AB  - We have previously described a unique type of delta beta-thalassemia in a Chinese
      family characterized by increased expression of the G gamma and A gamma fetal
      globin genes in the absence of a large deletion in the beta-globlin gene cluster.
      Our earlier study of the beta-globin gene on this delta beta-thalassemia
      chromosome showed a promoter mutation in the TATA box. In this report, we
      describe the results of our study of the fetal globin domain of this delta beta
      thalassemia chromosome. We have cloned a 13-kb DNA fragment that includes the G
      gamma and the A gamma genes and the 3' A gamma enhancer element of this delta
      beta-thalassemia chromosome. DNA sequence analysis of the G gamma and A gamma
      globin genes including their promoters did not show any mutations, but analysis
      of the putative enhancer element downstream from the A gamma-globin gene showed a
      C to T substitution 2,401 nucleotides downstream from the A gamma cap site. We
      performed DNA linkage analysis to determine if this mutation is unique to this
      chromosome or represents a common polymorphism. Our linkage analysis showed that
      this mutation is not a common polymorphism and that it is also not an intrinsic
      part of the haplotype of the chromosome on which it was found. We also studied
      the interaction of nuclear proteins from erythroid and nonerythroid cells with
      the DNA sequences surrounding this mutation. We have shown by in vitro DNase I
      footprinting that this mutation falls within a region that is occupied by a novel
      DNA-binding protein that binds to this site in nuclear extracts from erythroid,
      but not nonerythroid cells. The binding of this nuclear protein to DNA appears to
      be dependent on GATA-1 binding to an adjacent GATA-1 site. We have also developed
      a new functional assay to compare the activity of the normal and mutant A gamma
      enhancer elements in erythroid cells. Analysis of the activity of the mutant
      enhancer shows that the mutation completely eliminates all enhancer activity in
      this assay. These findings suggest that this mutation of the A gamma enhancer on
      a chromosome that carries a partially inactivated beta-globin gene may be
      responsible for the increased expression of both gamma-globin genes seen in this
      condition.

PMID- 7515721
TI  - Patient characteristics associated with successful mobilizing and autografting of
      peripheral blood progenitor cells in malignant lymphoma.
AB  - For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose
      therapy with peripheral blood progenitor cell (PBPC) support may become a first
      line treatment. The duration of severe cytopenia in this setting is inversely
      related to the number of PBPCs autografted. In a retrospective analysis, we
      therefore looked for factors influencing the yield of PBPCs in 61 patients (16
      with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL],
      and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim
      (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6
      micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45
      were in partial remission (PR) or complete remission (CR) after conventional
      therapy. A median of three leukaphereses (range, one to 10) resulted in a median
      of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic
      chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each
      cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+
      cells/kg per leukapheresis in nonirradiated patients, while large-field
      radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg
      CD34+ cells. The collection efficiency was also significantly lower in patients
      with Hodgkin's disease. However, except for one, all had been previously
      irradiated. In contrast, age, sex, disease status, bone marrow involvement during
      mobilization, and the time since the last chemotherapy or radiotherapy were not
      significantly related to the collection efficiency. Following high-dose
      conditioning therapy, 42 patients were autografted with filgrastim-mobilized
      PBPCs. Hematological recovery (neutrophils > or = 0.5 x 10(9)/L and an
      unsupported platelet count > or = 20 x 10(9)/L) within 2 weeks was observed in
      patients autografted with > or = 2.5 x 10(6) CD34+ cells/kg. In seven patients,
      the quantity of CD34+ cells reinfused was below this threshold. They required a
      median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil
      and platelet recovery, respectively. If autografting with PBPCs in malignant
      lymphoma with poor prognosis is being considered, mobilization and harvesting
      should be planned early after initial diagnosis to avoid exhaustion of
      hematopoiesis by cumulative toxicity.

PMID- 7515720
TI  - Eastern European (delta beta) zero-thalassemia: molecular characterization of a
      novel 9.1-kb deletion resulting in high levels of fetal hemoglobin in the adult.
AB  - A novel deletion in the human beta-globin gene cluster associated with increased
      levels of fetal hemoglobin (HbF) in adult life was molecularly characterized in a
      member of a family of Eastern European descent. The phenotype of the deletion,
      documented in five members of the family, shows mild hypochromia and microcytosis
      (mean corpuscular Hb, 24 to 25.9 pg; mean corpuscular volume, 74 to 78.5 fL) but
      high production of HbF (13% to 24%) with heterocellular distribution (36% to 86%
      F cells). Extensive restriction enzyme mapping of the beta-globin cluster and
      sequencing of the region encompassing the breakpoints showed that the deletion
      starts 1,612 bp upstream of the cap site of the delta-globin gene, and terminates
      within the first intron of the beta-globin gene, deleting 9.1 kb of DNA. This
      length is definitely shorter than the average 12.0 kb of the previously
      characterized (delta beta) zero-thalassemias. The 5' breakpoint of the new
      deletion is close to that of the Yugoslavian delta beta-thalassemia deletion,
      whereas the 3' breakpoint is very close to those of the Turkish and the Greek
      beta zero-thalassemia deletions. The breakpoints of the deletion occur within a
      direct repeat containing a tetranucleotide exhibiting homology to a donor-splice
      site, and is symmetrically flanked by a set of 13- and 14-bp homologous
      complementary sequences, respectively. It is likely that the deletion may be the
      result of an "illegitimate" or "nonhomologous" recombination event to which these
      two short sequences may have contributed. It is of interest that the novel
      deletion (9.1 kb) is comparable to the Italian HPFH-5 deletion (12.9 kb),
      regarding both the size and the position of the breakpoints. However, the HPFH-5
      deletion includes sequences flanking the breakpoints that are preserved in the
      new deletion. Considering the resulting two discrete phenotypes (ie, delta beta
      thalassemia v HPFH), it can be hypothesized that the deleted sequences in the
      Italian HPFH-5 mutation may harbor regulatory elements that exert a negative
      control on the gamma-globin gene expression.

PMID- 7515722
TI  - Effects of granulocyte colony-stimulating factor and stem cell factor, alone and
      in combination, on the mobilization of peripheral blood cells that engraft
      lethally irradiated dogs.
AB  - The effects of recombinant canine granulocyte colony-stimulating factor (rcG-CSF)
      and recombinant canine stem cell factor (rcSCF), a c-kit ligand, on the
      circulation of hematopoietic progenitor and stem cells were studied in a canine
      model. Administration of rcG-CSF (10 micrograms/kg) for 7 days led to a 5.4-fold
      increase in CFU-GM/mL of blood, while 7 days of rcSCF (200 micrograms/kg) led to
      an 8.2-fold increase. Although treatment with low-dose rcSCF (25 micrograms/kg)
      had no effect on the level of peripheral blood progenitors, 7-day exposure to a
      combination of G-CSF plus low dose SCF led to a 21.6-fold increase (P = .03). To
      assess the ability of these factors to increase the circulation of cells capable
      of rescuing animals after lethal total body irradiation (TBI), 1 x 10(8)
      peripheral blood mononuclear cells (PBMC)/kg were collected and cryopreserved
      from animals after 7 days of treatment with G-CSF, SCF or a combination of the
      two. One month later, animals were exposed to 9.2 Gy TBI and transplanted with
      the previously collected cells. Control animals transplanted with 1 x 10(8)
      PBMC/kg collected without pretreatment died with marrow aplasia 11 to 29 days
      after TBI as did animals treated with only low-dose SCF before cell collection.
      In contrast, all animals given PBMC collected after G-CSF, high-dose SCF, or a
      combination of G-CSF plus low-dose SCF recovered granulocyte function. Recovery
      to 500 granulocytes/microL after transplant took 17, 18.8, and 13.6 days,
      respectively, (P = .056 for the difference between the combination G-CSF-SCF
      group and the other two groups). In both the G-CSF and SCF groups, 4 of 5 animals
      completely recovered while 1 of 5 in each group died with prolonged
      thrombocytopenia. In the combination group, all 5 animals became long-term
      survivors. These studies demonstrate that both G-CSF and SCF dramatically
      increase the level of peripheral blood hematopoietic progenitor and stem cells
      and support the view that these factors can act synergistically.

PMID- 7515723
TI  - In vivo blockade of CD28/CTLA4: B7/BB1 interaction with CTLA4-Ig reduces lethal
      murine graft-versus-host disease across the major histocompatibility complex
      barrier in mice.
AB  - We tested whether the in vivo infusion of recombinant, soluble CTLA4 fused with
      Ig heavy chains, as a surrogate ligand used to block CD28/CTLA4 T-cell
      costimulation, could prevent efficient T-cell activation and thereby reduce graft
      versus-host disease (GVHD). Lethally irradiated B10.BR recipients of major
      histocompatibility complex disparate C57BL/6 donor grafts received
      intraperitoneal injections of human CTLA4-Ig (hCTLA4-Ig) or murine CTLA4-Ig
      (mCTLA4-Ig) in various doses and schedules beginning on day -1 or day 0 of bone
      marrow transplantation (BMT). In all five experiments, recipients of CTLA4-Ig had
      a significantly higher actuarial survival rate compared to mice injected with an
      irrelevant antibody control (L6) or saline alone. Survival rates in recipients of
      hL6 or PBS were 0% at 29 to 45 days post-BMT. In recipients of CTLA4-Ig, survival
      rates were as high as 63% mice surviving 3 months post-BMT. However, protection
      was somewhat variable and recipients of CTLA4-Ig were not GVHD-free by body
      weight, clinical appearance, and histopathologic examination. There were no
      significant differences in the survival rates in comparing injection dose,
      injection duration, or species of CTLA4-Ig (hCTLA4-Ig v mCTLA4-Ig). Splenic and
      peripheral blood flow cytometry studies of long-term hCTLA4-Ig-injected survivors
      showed a significant peripheral B-cell and CD4+ T-cell lymphopenia, consistent
      with GVHD. A kinetic study of splenic reconstitution was performed in mice that
      received hCTLA4-Ig and showed that mature splenic localized CD8+ T-cell
      repopulation was not significantly different in recipients of hCTLA4-Ig compared
      with hL6, despite the significant increase in actuarial survival rate in that
      experiment. These data suggest that the beneficial effect of hCTLA4-Ig on
      survival is not mediated by interfering with mature donor-derived T-cell
      repopulation post-BMT. Neither hCTLA4-Ig nor mCTLA4-Ig interfered with
      hematopoietic recovery post-BMT. We conclude that CTLA4-Ig (most likely in
      combination with other agents) may represent an important new modality for GVHD
      prevention.

PMID- 7515724
TI  - Genetics of nanos localization in Drosophila.
AB  - The Drosophila gene nanos is required for two processes. During oogenesis, nanos
      function is required for the continued production of egg chambers, and nanos is
      expressed in the early germarium. During embryogenesis, nanos is required
      maternally to specify abdominal segmentation. Nanos shares this latter function
      with nine other genes, collectively known as the posterior group. Of this group,
      nanos encodes a determinant, and is localized as an RNA to the posterior pole of
      early embryos. This RNA is translated to form a gradient of nanos protein with
      highest concentrations at the posterior. Analysis of the distribution of nanos
      gene products in embryos mutant for posterior group genes shows that eight of
      these genes are required for localization, but not stability, of the nanos RNA.
      Embryos mutant for posterior group alleles which produce weak abdominal
      phenotypes show reduced amounts of localized nanos RNA. This correlation between
      nanos RNA localization and abdominal phenotype suggests that nanos acts as a
      localization-dependent posterior determinant. Localization of nanos is not
      affected by mutations in bicoid or torso, confirming that the three maternal
      systems of anterior-posterior determination initially act independently.

PMID- 7515725
TI  - Differentiation, extracellular matrix synthesis, and integrin assembly by
      Drosophila embryo cells cultured on vitronectin and laminin substrates.
AB  - Two contrasting substrates, Drosophila laminin and human vitronectin, caused
      determined primary Drosophila embryo cells to follow alternate intermediate
      differentiation steps without affecting the final outcome of differentiation.
      Integrin alpha PS2 beta PS3 was essential for the initial spreading of myocytes
      on vitronectin: focal contacts rich in beta PS3 integrins formed and were
      connected by actin- and myosin-containing stress fibers. While alpha PS2 beta PS3
      was unnecessary for myotube formation on laminin, it was required for the
      subsequent change to a sarcomeric cytoarchitecture. The differentiating primary
      cultures synthesized integrins and assembled them into detergent-insoluble,
      cytoskeleton-associated complexes. Collagen IV, laminin, glutactin, papilin, and
      other extracellular matrix proteins were made primarily by hemocytes and were
      secreted into the medium. Further differentiation within the cultures was
      influenced by secreted components and by later addition of vitronectin or bovine
      serum. Comparison of the differentiation of various cell types on the two
      substrates showed that vitronectin provided a selective advantage for the
      differentiation of myocytes, with enrichment over epithelia, epidermal cells, and
      neurites.

PMID- 7515726
TI  - Dynamic expression patterns of tenascin, proteoglycans, and cell adhesion
      molecules during human hair follicle morphogenesis.
AB  - The development of skin appendages such as hair, feathers, and teeth is brought
      about by reciprocal interactions between epidermal and mesenchymal tissues and is
      thought to be influenced in part by cell adhesion molecules and components of the
      extracellular matrix. The developmental distributions of tenascin, neural cell
      adhesion molecule (NCAM), E-cadherin, intercellular adhesion molecule 1 (ICAM-1),
      chondroitin sulfate proteoglycan (CSPG), and the heparan sulfate proteoglycan
      perlecan were studied in relation to hair follicle morphogenesis in fetal human
      skin. Tenascin first appeared in developing skin in focal concentrations at the
      epidermal-mesenchymal interface, just prior to, and presumably correlated with,
      hair follicle initiation. Tenascin immunostaining remained prominent in the
      basement membrane zone and extracellular matrix of the follicle sheath during
      subsequent morphogenetic stages. Two forms of tenascin (M(r) 250 x 10(3) and 280
      300 x 10(3)), were revealed by Western blots of skin extracts. NCAM
      immunolabeling was initially present throughout the dermis, and became
      progressively restricted to the dermal condensation and the follicle sheath.
      Western blot analysis revealed an isoform of NCAM (M(r) 160 x 10(3)) which lacked
      polysialic acid. At all stages, E-cadherin staining was diminished on follicle
      cells situated adjacent to the basement membrane, relative to cells in the
      follicle interior. Follicle-specific immunostaining for ICAM-1 was transient,
      appearing only at the pre-germ and hair germ stages of development. Antibodies to
      three distinct CSPG determinants revealed unique immunolabeling patterns
      following follicle initiation: One CSPG epitope co-distributed with tenascin in
      the follicle basement membrane and follicle sheath extracellular matrix; one CSPG
      epitope was similarly expressed, and was also found on follicle epithelial cells;
      and the third CSPG determinant was noticeably absent from the follicle sheath
      during elongation of the developing appendage. Perlecan was concentrated in the
      dermal papilla, in addition to its distribution in all skin basement membranes. A
      model for how these diverse molecules may interact to influence human hair
      follicle morphogenesis is presented.

PMID- 7515727
TI  - Alternative splicing of bovine terminal deoxynucleotidyl transferase cDNA.
AB  - Two cDNA fragments of terminal deoxynucleotidyl transferase, which contained new
      insertion sequences, were found from bovine thymus cDNA. One of the clones
      encoded 18 new amino acids and the other encoded 9 new amino acids. In the
      results of genomic structure analysis around the new insertion sequences,
      alternative splicing of the bovine terminal deoxynucleotidyl transferase gene was
      suggested.

PMID- 7515728
TI  - [Does oncogene c-ets 1 participate in the regulation of tumor angiogenesis?].
AB  - The formation of new blood vessels is an essential process in embryonic
      development and wound healing, for tumor growth and metastasis. In situ
      hybridization studies have revealed that the protooncogene c-est1 is expressed in
      endothelial cells at the beginning of blood vessel formation, in normal and
      pathological conditions. c-ets1 encodes a transcription factor, a protein which
      binds specifically to DNA and which regulates the transcription of genes
      containing these specific binding sequences in their promotors. Thus, in vitro
      experiments suggest that c-ets1 may activate the transcription of genes encoding
      collagenase 1, stromelysine 1 and urokinase plasminogen activator, proteases
      involved in extracellular matrix degradation. A working hypothesis is that c-ets1
      takes part in regulating angiogenesis by controlling the transcription of these
      genes whose activity is necessary for the migration of endothelial cells from pre
      existing capillaries. This hypothesis is discussed with respect to current
      experimental evidence and to the complexity of the regulatory network controlling
      gene transcription and extracellular matrix degradation.

PMID- 7515730
TI  - [Results of a combination of platinum-vindesin-ametycin-bleomycin (CEMB) in the
      treatment of stage IV non-small-cell lung cancers].
AB  - From July 1987 to July 1988, 35 patients with non small cell lung cancer, stage
      IV, were included in a phase II trial (GLOT NPC 87/01). The treatment was as
      follows: cisplatin 50 mg/m2 day 1, vindesin 3 mg/m2 day 1, mitomycin 6 mg/m2 day
      2, and bleomycin 15 mg/day, day 1 + 2 by continuous infusion. The evaluation for
      response was assessed after three courses of chemotherapy. The results were poor:
      an objective response was observed in three patients: three partial responses and
      no complete response. Because of tumor progression (18 patients) or toxicity
      (three patients), 21 patients did not complete the three cycles of chemotherapy.
      The median survival rate was 100 days. Toxicity was mild: grade III neutropenia
      occurred in one patient, grade IV thrombocytopenia was also observed in one
      patient. We conclude that this treatment has only a poor efficacy in stage IV non
      small cell lung cancer.

PMID- 7515729
TI  - [Chemotherapy of cancers of the uterine cervix with a combination of bleomycin,
      mitomycin, cisplatin and etoposide].
AB  - Sixty patients with advanced carcinoma of the cervix were treated with 3-week
      cycles of chemotherapy consisting of bleomycin (10 mg/m2, D1, 2, 3), mitomycin
      (10 mg/m2, D1), cisplatin (80 mg/m2, D3), etoposide (100 mg/m2, D1, 2, 3). Twenty
      six patients had prior therapy. Toxicities noted were primarily nausea, vomiting,
      asthenia, fever and myelosuppression, especially in the pre-treated patients. One
      patient died of pulmonary toxicity. Of the 34 untreated patients, 25 objective
      responses (74%) were observed, with two complete responses (6%) and among the 26
      pre-treated patients, ten objective responses (39%) with only one complete
      response. The mean duration of response was 3.8 months [2-14]. These data
      indicate that combination chemotherapy regimen is active against advanced and
      recurrent cervical cancer but caution is required for administration and
      continuation of treatment after four cycles. This method of chemotherapy has
      significant potential for primary treatment in patients with locally advanced
      disease.

PMID- 7515732
TI  - [Use of fluorine-19 nuclear resonance spectroscopy for the measurement of changes
      induced in blood perfusion volume in experimental tumors in vivo].
AB  - The biological response of some anti-cancer therapeutic agents is probably
      mediated via the tumour vasculature. A novel approach using 19F NMR spectroscopy
      in vivo has been developed to directly measure changes in vascular perfusion
      volume in experimental tumours. A 100% w/v perfluorooctylebromide (PFOB) emulsion
      was used as a tracer. For a fixed position of a 7 mm surface coil placed over the
      tumour, the signal from the PFOB rapidly reached an equilibrium value remaining
      unchanged for at least 2 hours. Since the strength of the fluorine signal is
      directly proportional to the perfusion volume of the tumour vasculature,
      reduction of signal intensity should correspond directly to any reduction in
      volume which may be a manifestation of a change in the tumour blood flow. This
      hypothesis was investigated using hydralazine as a physiological modifier of
      tumour blood flow. Administration of 5 mg/kg of hydralazine following dosing with
      the PFOB emulsion reduced the 19F signal intensity from the murine tumors RIF-1
      and KHT and from the human tumour HT29 with no or little reduction in the
      SCCVII/Ha murine and HX118 human tumours. Changes in blood volume in KHT tumour
      accompanied local changes in tumour blood flow rate as measured by the Xe-133
      clearance rate technique. Thus, these data demonstrate the potential of the PFOB
      emulsion as a 19F NMR tracer of the vasculature to measure changes induced by
      therapeutic agents on blood volume in accessible tumours. This method may also be
      useful to detect early changes in blood volume produced during angiogenesis of
      solid tumours or angiostatic activity of anti-cancer drugs.

PMID- 7515731
TI  - [CD44, the hyaluronic acid cell receptor. Its role in neoplastic invasion and
      metastatic dissemination].
AB  - The CD44 group of transmembrane glycoproteins encompasses several isoforms
      expressed in a variety of tissues. All isoforms are encoded by the same gene on
      chromosome 11 and are formed by alternative splicing of their mRNA. CD44 isoforms
      belong to the family of cell adhesion molecules and to the sub-family of the
      hyaladherins in consideration of their affinity for hyaluronate and their
      structural homology with the cartilage link protein. The standard form of CD44,
      CD44H exhibits a high affinity for hyaluronate, plays a role in the uptake and
      degradation of this glycosaminoglycan and participates in cell locomotion in its
      presence. In physiology, CD44H plays a role in the homing of lymphocytes into
      Peyer's patches, in organogenesis and in the degradation of hyaluronate in lung
      or lymphoid tissue. In pathology, CD44H probably enhances the tumorigenic
      properties of some lymphomas and melanomas. The variant form CD44E exhibits low
      affinity for hyaluronate and its role in cell-cell adhesion in epithelia is
      suspected. The variant form CD44V (or CD44M) confers metastatic properties to rat
      carcinoma cells and is expressed in human breast and colorectal cancer and in
      adenomatous polyps.

PMID- 7515733
TI  - [Interferons, a class of cytokines with a large therapeutic activity range].
AB  - Initially discovered as antiviral agents, the interferons (IFNs) proved to be a
      class of cytokines with multifunctional properties, including inhibition of cell
      growth and modulation of immune functions. A number of clinical trials were thus
      carried out in cancer and viral diseases, and IFN-alpha therapy was shown to have
      a wide range of indications in hematology and dermatology: B-cell malignancies
      (hairy cell leukemia, non-Hodgkin's lymphoma, multiple myeloma),
      myeloproliferations (chronic myeloid leukemia, thrombocytosis), cutaneous T
      lymphoma, basal-cell carcinoma, cutaneous squamous cell carcinoma, Kaposi's
      sarcoma. IFN therapy also showed efficacy in viral tumors (condyloma acuminatum
      and laryngeal papillomatosis) and chronic hepatitis B and C. The antitumoral
      action of IFN-alpha mainly involves its capacity to inhibit cell proliferation,
      partly via antagonistic effects on growth factors. The elucidation of IFN-alpha
      signalling pathway(s) leading to gene activation, a better understanding of the
      interactions between IFN-alpha and cytokine network, and the development of
      combination therapy with other biological treatments or chemotherapy should
      greatly improve the clinical use of IFNs.

PMID- 7515734
TI  - [Heterocomplex formation between high and low affinity FGF receptors is mediated
      by the formation of a FGF dimer].
AB  - Interactions between the two classes of fibroblast growth factor receptors 1) the
      high affinity receptors (HAR) a membrane glycoprotein containing an intrinsic
      tyrosine kinase activity, 2) low affinity receptors (LAR) cell surface
      proteoglycans containing heparan sulfate side chains (HSPG), and aFGF (MW: 15.5
      kDa) were studied in bovine lens epithelial (BEL) cells. By Scatchard analysis of
      the aFGF binding to the BEL cell surface, we show that heparin at 10
      micrograms/ml abolishes completely aFGF binding to LAR and reduces by half the
      number of aFGF HAR. By using cross-linking experiments, aFGF-HAR complexes are
      present in two forms (150 kDa and 135 kDa). Addition of heparin at 10
      micrograms/ml abolishes the formation of the 150 kDa complex and does not affect
      the 135 kDa complex. Furthermore, binding of aFGF to LAR induces the spontaneous
      formation of a 31 kDa aFGF dimer. The dimerization process of aFGF on LAR is
      abolished by addition of heparin. During aFGF internalization at 37 degrees C, we
      have shown that aFGF-dimer is internalized, accumulated and degraded in the cell
      as is the 15.5 kDa native form. Heparin at 10 micrograms/ml suppresses
      specifically aFGF dimer internalization and reduces by half the total amount of
      internalized aFGF native form. Moreover, after aFGF binding and internalization,
      the affinity of HAR for aFGF increases concomitantly with its downregulation.
      Heparin does not seem to affect this phenomenon. All these results strongly
      suggest that an heteroreceptor dimer-aFGF complex (150 kDa) is formed by one
      molecule of HAR associated to one molecule of LAR through their respective
      interaction with a very stable homodimer of aFGF. Such a three component receptor
      complex induced by FGF dimerization may be a general process of FGF receptor
      activation which could explain the diversity of the biological response to FGF of
      different cell type expressing different HAR and LAR or HSPG.

PMID- 7515735
TI  - [Treatment of high malignancy lymphoma with intensive short-term chemotherapy
      using the MACOP-B regimen].
AB  - We present our results of a MACOP-B regimen in a series of 46 patients with high
      grade NHL. The complete remission rate was 74% for patients with advanced stage
      disease. The excellent tolerance allowed this regimen to be given on an
      outpatient basis in the majority of cases. The median follow-up for the living
      patients is 28 months. Although some patients received additional treatment that
      could influence the results, the predicted DFS (disease-free survival) at 45
      months of 57% compares favorably with the best results published so far with more
      toxic regimens.

PMID- 7515737
TI  - The effect of paroxetine on cerebrospinal fluid concentrations of
      neurotransmitter metabolites in depressed patients.
AB  - This paper describes the effect of the selective serotonin reuptake inhibiting
      drug (SSRI), paroxetine, on cerebrospinal fluid concentrations of
      neurotransmitter metabolites in depressed patients. 5-Hydroxyindoleacetic acid (5
      HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were
      measured at baseline and after 3 weeks of treatment with 30 mg paroxetine daily.
      In line with similar studies on other SSRIs, influence on both the serotonin and
      noradrenaline metabolite was found. The mechanism behind the action of paroxetine
      on both 5-HIAA and MHPG is assumed to be an expression of the linkage between the
      serotonergic and noradrenergic systems in the brain. A frequently reported
      correlation between 5-HIAA and HVA was also found. The analysis of paroxetine in
      CSF proves the transportation of the drug into the central nervous system.

PMID- 7515736
TI  - Immunological mechanism of chronic liver injury in viral hepatitis.
AB  - Chronic hepatitis B and chronic hepatitis C centering on immunohistochemical
      studies of the liver were investigated as possible mechanisms of the chronicity
      of viral hepatitis. Although liver cell injury was presumed to be caused by CTL
      in both chronic hepatitis B and C, other mechanisms of cell injury were also
      presumed with chronic hepatitis, type C, including autoimmune mechanisms.

PMID- 7515738
TI  - Radioimmunoassays for IGFs and IGFBPs.

PMID- 7515739
TI  - Insulin-like growth factor binding proteins: a review of methodological aspects
      of their purification, analysis and regulation.
AB  - The reason why there are at least 6 distinct high affinity IGFBPs is obviously a
      great challenge for investigators to unravel. In order to undertake this
      challenge a wide range of techniques have now been developed for investigating
      IGFBPs. As the IGFBPs have been characterized it has become clear that they are
      complex multi-faceted molecules; the more tools that can be applied to examine
      them, the better are the chances for getting a complete picture. The return for
      the investment of all this technology is the hope that elucidation of the
      sophisticated system of IGFBPs will provide a much better understanding of how
      the pluripotential actions of the ubiquitous IGFs can be most appropriately
      regulated in a manner specific to each tissue and according to developmental and
      environmental conditions.

PMID- 7515740
TI  - Secondary myelodysplastic syndrome following bone marrow transplantation: report
      of two cases.
AB  - We report two cases of secondary myelodysplastic syndrome (SMDS) which followed
      successful treatment of a primary malignancy with high-dose chemotherapy
      supported by reinfusion of autologous stem cells. The SMDS was diagnosed 24
      months and 40 months, respectively, following autografting. Both patients lived
      for 7 months after the diagnosis of SMDS. Our cases support the view that there
      is an increased risk of SMDS/acute leukemia following autologous marrow
      transplantation.

PMID- 7515741
TI  - Marked increase of CD8+S6F1+ and CD8+CD57+ cells in patients with graft-versus
      host disease after allogeneic bone marrow transplantation.
AB  - Peripheral blood lymphocytes (PBL) from 24 allogeneic bone marrow transplant
      (BMT) recipients were studied serially using flow cytometry and two-color
      analysis. Dual labelling with two monoclonal antibodies (moAbs), CD8/S6F1 (CD11a)
      and CD8/CD57 was used to analyze the surface phenotypes of PBL after allogeneic
      BMT. In patients with acute and chronic GVHD, CD8+S6F1+ cells were markedly
      increased from the onset of GVHD and recovered to normal range 6 years after
      transplantation. By contrast, CD8+S6F1- cells fell below normal range and
      remained markedly decreased for 2-3 years after transplantation in patients with
      acute and chronic GVHD. A slight but significant increase of CD8+CD57- cells was
      observed with clinical signs of acute GVHD. On the other hand, CD8+CD57+ cells
      were increased after the onset of acute and chronic GVHD and recovered to normal
      range 6 years after transplantation. These results suggest that these subsets of
      CD8+ cells may play important roles in the pathophysiology of GVHD.

PMID- 7515743
TI  - Inhibition of human immunodeficiency virus proliferation by macrocyclic
      polyamines and their metal complexes.
AB  - The macrocyclic polyamines, cyclen and cyclam, and their derivatives have been
      tested for inhibitory activity against the cytopathogenic effect (CPE) of human
      immunodeficiency virus type 1 strain HTLV-IIIB (HIV-1IIIB) on CD4+ human
      lymphoblastoma MT-4 cells. Cyclam and its derivatives were complexed with a
      variety of transition metal ions NiII, ZnII, CuII, FeIII and CoIII. The divalent
      metal complexes effected lower toxicity and greater anti-HIV-1 activity, while
      the trivalent metal complexes had no effect on HIV-1-dependent CPE. When
      dimerized, the anti-HIV activity of monomers was significantly enhanced. A potent
      inhibition of CPE by biscyclam was transiently observed 4 d after the virus
      infection, but was not seen at 6 d due to severe toxicity. The toxicity of
      biscyclam, referred to as delayed toxicity, could be overcome by a metal
      complexation. The strain specificities of biscyclams were further studied by
      testing their effects on syncytium formation between HIV-infected and uninfected
      human acute lymphoblastic leukemia MOLT-4 cells. The 50% inhibitory
      concentrations of biscyclams against HIV-2GH-1-dependent syncytium formation were
      less than one hundredth those for the other HIV strains (HIV-1IIIB, HIV-1RF and
      HIV-1SF-2).

PMID- 7515742
TI  - The induction of interleukin-6 (IL-6) and colony-stimulating factors (CSFs) by
      FK565 and its thrombopoietic activity following in vivo administration.
AB  - The induction of macrophage colony-stimulating factor (M-CSF) in monkey plasma
      following administration of FK565 was observed within 2 h of injection peaked at
      4 h, and remained high after 24 h. Interleukin-6 (IL-6) and M-CSF levels
      increased in monkeys treated with FK565, even at doses as low as 0.01 mg/kg.
      Granulocyte CSF (G-CSF) levels increased slightly following a dose of 1 mg/kg,
      but granulocyte macrophage CSF (GM-CSF) was not detected at any doses of FK565
      studied. To examine the thrombopoietic activity of FK565 in vivo, single doses of
      drug (0.01, 0.1 or 1.0 mg/kg) were administered i.v. to cynomolgus monkeys or
      normal mice on day 0. The promotes platelet (PLT) count after FK565 injection
      decreased transiently on days 1 and 2, and then increased in a dose-dependent
      manner on day 5 and was still high on day 14. The experiment using anti-PLT
      antibody showed that the increased PLT count was not simply due to a rebound
      phenomenon after the transient decrease in PLT. The effect of i.v. FK565 was
      studied in mice myelosuppressed with a single dose of mitomycin C (MMC) (5.6
      mg/kg). The fall in PLT count was suppressed on day 7 by 0.1 and 1.0 mg/kg FK565.
      Although intact cells or tissues are necessary for an increase in PLT following
      FK565 treatment, FK565 suppressed the impaired hematopoietic function seen after
      chemotherapy. FK565 is proposed as a drug to restore reduced neutrophil and
      platelet counts found in AIDS or cancer therapy.

PMID- 7515744
TI  - Anti-inflammatory activities of methanolic extract and alkaloidal components from
      Corydalis tuber.
AB  - A methanolic extract (CM-ext) from Corydalis tuber (Corydalis turtschaninovii
      Besser forma yanhusuo Y. H. Chou et C. C. Hsu) has been screened for activity in
      experimental models of inflammation. CM-ext (200 or 500 mg/kg, p.o.) inhibited an
      increase in vascular permeability in mice induced by acetic acid, and reduced
      acute paw edema in rats induced by compound 48/80 or carrageenin. CM-ext
      suppressed the development of adjuvant-induced edema in arthritic rats. CM-ext
      and its alkaloidal components, dehydrocorydaline, d-glaucine and l
      tetrahydrocoptisine inhibited compound 48/80-induced histamine release from
      peritoneal mast cells of rats. Since these substances from C. tuber were found to
      be effective in both the acute and chronic phases of inflammation, the crude drug
      C. tuber can be considered to exert anti-inflammatory activity.

PMID- 7515745
TI  - Manipulation of renal disposition of human recombinant superoxide dismutase by
      chemical modification.
AB  - The renal disposition characteristics of superoxide dismutase (SOD) and its
      derivatives, including macromolecular conjugates with polyethylene glycol and
      carboxymethyl-dextran, a cationized derivative, and glycosylated derivatives with
      galactose and mannose, were studied in the isolated perfused rat kidney. Renal
      disposition processes, such as glomerular filtration, tubular reabsorption, and
      uptake from the capillary side, were quantitatively determined by single-pass
      indicator dilution experiments under filtering and nonfiltering kidney
      conditions. Native SOD had a high glomerular filtration rate (40% of that of
      inulin) and was effectively reabsorbed in the tubules, while no significant
      uptake was observed from capillary side. Macromolecular conjugates showed
      restricted glomerular filtration due to an increase in molecular size.
      Cationization of SOD greatly enhanced its association with the tissue, not only
      from the luminal side but also from the capillary side, based upon electrostatic
      interaction. Galactosylated and mannosylated SOD showed reduced tubular
      reabsorption and increased exposure of the luminal surface to the enzyme. In
      addition, a small but significant uptake of mannosylated SOD from the capillary
      side was observed. This uptake was dose-dependent and completely inhibited by
      mannan, suggesting that mannose receptor-mediated endocytosis existed in the
      capillary side of the kidney. Thus, we can manipulate the renal disposition
      profiles of SOD by changing its physicochemical or biological properties through
      chemical modification.

PMID- 7515746
TI  - Disposition of recombinant human insulin-like growth factor-I in normal and
      hypophysectomized rats.
AB  - The pharmacokinetics of recombinant human insulin-like growth factor-I (rhIGF-I)
      was examined in normal and hypophysectomized (Hypox) rats after i.v.
      administration. The plasma concentration of rhIGF-I administered i.v. (0.32, 1.0
      and 3.2 mg/kg) declined biexponentially in both normal and Hypox rats. Half-lives
      of the beta-phase were not significantly different among the doses examined in
      both animal groups, but were shorter in Hypox rats. In Hypox rats, the values of
      the area under the plasma concentration-time curve, the mean residence time, the
      variance of residence time and the apparent volume of distribution at steady
      state decreased, while the total body clearance (CLtotal) increased. The
      distribution of rhIGF-I after i.v. administration (1.0 mg/kg) was examined in
      normal rats. High distribution to the kidney was observed at early time points (5
      min and 1 h), but no significant distribution was found in other tissues. The
      ligation of renal vasculature greatly reduced the CLtotal, suggesting that the
      kidney is the main elimination organ. In spite of the rapid distribution of rhIGF
      I to the kidney, the urinary excretion of intact rhIGF-I was negligible. Thus,
      the metabolism of rhIGF-I in the kidney was examined in vitro, and the results
      showed extensive metabolism in the brush border and lysosomal fractions of
      tubular cells. In the plasma of normal rats, rhIGF-I formed the 50 kDa complex
      first, and the 150 kDa complex was formed slowly.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7515747
TI  - Evaluation of enhancers to increase nasal absorption using Ussing chamber
      technique.
AB  - The effects of eight prospective absorption enhancers on the nasal mucosa in
      rabbit have been assessed using an in vitro Ussing chamber technique. Sodium
      taurodihydrofusidate (STDHF), sodium deoxycholate (DC), polyoxyethylene-9-lauryl
      ether (BL-9), lysophosphatidylcholine (LPC) and sodium dodecyl sulfate (SDS) were
      found to possess relatively high protein leaching activity, while sodium
      glycocholate (GC), sodium taurocholate (TC) and EDTA had relatively low activity.
      The permeation of fluorescein isothiocyanate-labeled dextran (FD, M.W. 9400) as a
      model drug across the nasal mucosa was found to be greater in the presence of
      these enhancers. Their enhancement ratio was found to be in the order of BL-9 >
      STDHF > SDS > LPC > DC > EDTA > GC > TC, which correlated with the protein
      leaching activity. The differences in protein leaching and enhancement ratio
      dependent on the magnitude of change of membrane resistance (delta Rm),
      indicating that these enhancers damaged the membrane and increased FD permeation.
      delta Rm thus appears to be a useful indicator by which one can estimate nasal
      mucosa damage by the enhancers.

PMID- 7515748
TI  - GCG: the analysis of RNA secondary structure.

PMID- 7515749
TI  - GCG: comparison of sequences.

PMID- 7515752
TI  - A syndrome of osteogenesis imperfecta, optic atrophy, retinopathy and severe
      developmental delay in two sibs of consanguineous parents.
AB  - We report on two sibs of consanguineous parents with osteogenesis imperfecta,
      wormian bones, optic atrophy, retinopathy, fits and severe psychomotor
      retardation.

PMID- 7515753
TI  - An interstitial deletion of proximal 8q (q11-q13) in a girl with Silver-Russell
      syndrome-like features.
AB  - Silver-Russell syndrome (SRS) is characterized by pre- and postnatal growth
      retardation, a fine, triangular face, a high frontal hairline and prominent
      forehead, clinodactyly of the fifth fingers, and sometimes asymmetry of face,
      trunk and extremities. In a 10-year-old girl referred for SRS, cytogenetic
      examination disclosed a microdeletion of band 8q12. Dosage analysis of Southern
      blots hybridized to 8q markers revealed a deletion of three loci: MOS, D8S96 and
      D8S108, all mapping to 8q11-q12, however the deletion did not include PLAT (8q12
      q11). PCR analysis of the D8S166 microsatellite (8q11-q12) showed the lack of
      paternal inheritance, indicating that the deletion occurred in the paternal
      chromosome. The patient showed prenatal and postnatal growth retardation, mild
      developmental delay, microcephaly, a triangular face with high frontal hairline,
      shallow supraorbital ridges, hypoplastic alae nasi, small and prominent ears,
      prominent lateral palatine ridges, clinodactyly and brachymesophalangy of the
      fifth fingers. There were normal female genitalia and no asymmetry or detectable
      malformations. Screening of 19 other patients with the SRS for a similar
      cytogenetic and/or molecular deletion at 8q12 and for uniparental disomy 8 was
      negative. However, 8q12 still remains as one potential locus for a gene whose
      mutations may cause the clinical findings of SRS and which could be included in a
      larger deletion in a proband who has additional mild mental retardation.

PMID- 7515750
TI  - Fractionation of central nervous system myelin proteins by reversed-phase high
      performance liquid chromatography.
AB  - Chromatographic fractionation of central nervous system myelin proteins is
      hampered by their poor solubility in water and strong association with lipids.
      Moreover, several myelin membrane proteins undergo posttranslational acylation
      which further increases their hydrophobicity. Here, a method is described for a
      two-step delipidation and high-resolution fractionation by reversed-phase high
      performance liquid chromatography of all myelin proteins. The elution was
      monitored of the two major protein components, i.e. myelin basic protein (MBP)
      and proteolipid protein (PLP), as well as of minor components, viz. myelin
      associated glycoprotein (MAG) and myelin/oligodendrocyte glycoprotein (MOG).
      Whereas MBP and MOG elute as single sharp protein peaks upon chromatography, PLP
      and MAG are resolved into several different components. Following their
      delipidation and separation, all proteins including the hydrophobic transmembrane
      proteins can be transferred to fully aqueous solutions without detergents. The
      overall yield of myelin proteins obtained in this way exceeds 85%.

PMID- 7515751
TI  - Determination of two neuropeptide growth factor antagonists, [D-Arg1,D-Phe5,D
      Trp7,9,Leu11]-substance P and [Arg6,D-Trp7,9,N-MePhe8]- substance P(6-11), by
      high-performance liquid chromatography with electrochemical detection.
AB  - The neuropeptide growth factor antagonists [D-Arg1,D-Phe5,D-Trp7,9,Leu11]
      substance P (D) and [Arg6,D-Trp7,9, [corrected] N-MePhe8]-substance P(6-11) (G)
      are currently undergoing preclinical evaluation as potential anticancer agents
      and clinical trials are planned for G in the near future. A reversed-phase high
      performance liquid chromatographic separation has been developed which is both
      sensitive (limit of detection 250 pg/263 fmol for G; 500 pg/330 fmol for D) and
      selective, based on electrochemical detection of the two tryptophan residues
      present in each peptide. Two ion-pairing agents were included in the isocratic
      mobile phase to eliminate adsorption of the peptides onto the analytical column.
      Extensive sample clean-up procedures have been developed for plasma, tissue and
      tumour based on solid-phase extraction. Precision and accuracy of each assay was
      91.3 +/- 16.9% (between-day) for G and 99.3 +/- 16.9% (between-day) for D. The
      assays were able to detect the intact peptides and a number of their metabolites
      in plasma, liver and the WX 322 SCLC human xenograft in nude mice for at least 6
      hr after administration of therapeutic and pharmacological doses.

PMID- 7515754
TI  - A new syndrome: congenital thrombocytopenia, Robin sequence, agenesis of the
      corpus callosum, distinctive facies and developmental delay.
AB  - We present two female children with a distinctive pattern of malformation,
      including persistent thrombocytopenia, Robin sequence, agenesis of the corpus
      callosum, distinctive facies and developmental delay. We feel that these findings
      constitute a heretofore undescribed syndrome. Patient 1 presented during the
      newborn period with thrombocytopenia, Robin cleft, distinctive facies and
      agencies of the corpus callosum. Her thrombocytopenia has been persistent. Bone
      marrow aspirate showed adequate megakaryocytes. On follow-up she has mental
      retardation, microcephaly, growth delay and enamel hypoplasia. Patient 2 was also
      noted during the newborn period to have the Robin sequence, agenesis of the
      corpus callosum, a similar face to case 1 and persistent thrombocytopenia. Bone
      marrow aspirate showed decreased megakaryocytes. She also had delayed
      development, short stature, microcephaly and enamel hypoplasia. The combination
      of the Robin cleft, congenital onset of persistent thrombocytopenia and enamel
      hypoplasia appears particularly unique in combination. The aetiopathogenesis of
      this condition is unknown.

PMID- 7515755
TI  - Megakaryocytes and sinus walls in primary osteomyelofibrosis: transendothelial
      migration as revealed by three-dimensional reconstruction of serial sections
      following sequential double-immunostaining.
AB  - Using sequential double-immunostaining and a newly-developed three-dimensional
      (3D-) reconstruction technique on serially cut sections from bone marrow
      trephines, we studied the transmural passage of megakaryocytes through the sinus
      wall. Biopsies derived from patients with primary (idiopathic) osteomyelofibrosis
      were exposed to monoclonal antibody against type IV collagen to delineate the
      sinus walls and also the frequently thickened basement membrane. Staining with
      the primary antibody was followed by Y2/51 (CD61) to identify all elements of
      megakaryopoiesis. In most instances serial sectioning and 3D-reconstruction
      revealed an amoeboid shape of megakaryocytes and a tandem-like arrangement in
      close spatial contact with the abluminal surface of the sinus wall. Preceded by
      formation of cytoplasmic processes, straight penetration of entire megakaryocytes
      through gaps in the sinus walls into the lumen was seen. Where collagen deposits
      apparently presented a barrier, a mole-like tunnelling through the basement
      membrane material (type IV collagen) was recognizable. Our findings are in
      keeping with the assumption that megakaryocyte locomotion is an essential
      requirement for normal thrombocytogenesis.

PMID- 7515756
TI  - Demonstration of isolated follicular dendritic cells in lymphatic vessels around
      human immunodeficiency virus-infected lymph nodes.
AB  - Follicle lysis (FL) is a peculiar disruptive change of follicular dendritic cells
      (FDCs) commonly observed in the germinal centres of individuals with HIV
      infection. To clarify the fate of FDCs during FL, 30 HIV-infected lymph nodes
      were studied, mostly in the persistent generalized lymphadenopathy phase. FDCs
      were immunostained on paraffin sections with 1F8, a FDC-specific monoclonal
      antibody. In advanced FL, the FDC network was shown to be divided into cell
      clusters of various sizes. In the final phase of FL, these were fragmented into
      much smaller cell clusters and dispersed in the parafollicular area. Some of
      these small clusters were found in the lymphatic sinuses (6/30), and
      unexpectedly, even in extranodal lymphatic vessels (2/30, one being apparently
      located in efferent vessels). No efflux of these small FDC clusters into
      extranodal lymphatics was observed in 15 HIV-negative control lymph nodes. These
      FDC clusters located in the lymphatics may work as transporters of HIV to other
      lymph nodes downstream, as FDCs carry the greatest HIV load.

PMID- 7515760
TI  - Transurethral prostatectomy.

PMID- 7515759
TI  - Proteinase inhibitors of the Kunitz family in fallow deer organs: a comparative
      study.
AB  - Protein proteinase inhibitors belonging to the Kunitz family have been isolated
      and characterized in several fallow deer organs. In all the organs studied we
      found the basic pancreatic trypsin inhibitor (BPTI) while its isoforms,
      previously isolated and characterized in organs of other ruminant species (bovids
      and ovids), were absent. In the kidney, in addition to BPTI, active fragments of
      the inter-alpha-trypsin inhibitor were also isolated. The distribution of Kunitz
      type inhibitors in different species of ruminants is compared and discussed on
      the basis of the expression of their encoding genes.

PMID- 7515761
TI  - Effect of surgical trauma on muscle protein synthesis in the rat.
AB  - The rate of protein synthesis in skeletal muscle was measured in vivo in rats at
      various times during the first 2 days after abdominal surgery. Protein synthesis
      in abdominal muscle at the site of the wound was slightly reduced 2 h after
      operation, had returned to normal by 24 h and was massively increased by 48 h
      after surgery. In contrast, there was no change at any time in the rate of
      protein synthesis in either the gastrocnemius muscle or abdominal muscle distant
      from the wound site. Surgery had no effect on the weight or protein content of
      the gastrocnemius muscle, although urinary nitrogen excretion was increased
      relative to food intake, indicating the presence of a net catabolic response.
      Changes in whole-body protein turnover in response to uncomplicated abdominal
      surgery are thus likely to reflect the anabolic processes of wound healing and
      repair as well as any catabolic response in uninjured tissues.

PMID- 7515757
TI  - Cytomorphological, cytogenetic, and molecular biological characterization of four
      new human renal carcinoma cell lines of the clear cell type.
AB  - Four new permanent cell lines (RCC-A, -B, -C, and -D) derived from different
      human renal cell carcinomas of the clear cell type were established in tissue
      culture. The cell lines displayed characteristic differences in cell size and
      shape, which allowed individual identification by phase contrast microscopy.
      Ultrastructurally, the cell lines exhibited varying amounts of cytoplasmatic
      glycogen and lipid. Immunohistochemistry revealed co-expression of vimentin and
      cytokeratin in all cell lines. The mean population doubling time ranged from 27 h
      (RCC-A) to 104 h (RCC-D). RCC-B and -C cells produced slowly growing tumours
      after heterotransplantation into nude mice, whereas RCC-A and RCC-D cells were
      non-tumorigenic. The modal chromosome number was either near-diploid (RCC-A, -B,
      and -C) or near triploid (RCC-D). Clonal abnormalities affecting the short arm of
      chromosome 3 were seen in all cell lines. Northern blot analysis revealed no
      expression of the proto-oncogenes c-fos, c-ros, and c-mos, whereas c-Ki-ras
      expression was observed in all cell lines. Expression of c-myc was observed in
      RCC-A, RCC-B, and RCC-D cells, whereas c-raf expression could be detected in RCC
      B and RCC-D. Tumour suppressor gene p53 mRNA was observed in the cell line RCC-D.

PMID- 7515762
TI  - Amyloid beta protein-induced neuronal cell death: neurotoxic properties of
      aggregated amyloid beta protein.
AB  - The neurotoxic effects of soluble and aggregated synthetic amyloid beta protein
      (A beta P) have been investigated in rat primary cultures. Freshly solubilized
      beta(1-40) was neurotoxic not to immature, but to mature hippocampal neurons. On
      the other hand, aggregated beta(1-40) was neurotoxic to both. Neurotoxicity
      induced by aggregated beta(1-40) was 10-fold more potent than soluble beta(1-40)
      and was not prevented by substance P. The neurotoxicity of aggregated beta(1-40)
      to cultured neurons depended on the peptide concentration and the duration of
      exposure to it. Cerebral cortical and hippocampal neurons were significantly
      susceptible to aggregated beta(1-40) than cerebellar granular cells, and cultured
      astrocytes were not vulnerable to aggregated beta(1-40) even at high
      concentrations.

PMID- 7515763
TI  - Calcium-activated potassium channels in rat visceral sensory afferents.
AB  - The purpose of the present study was to describe, at the single-channel level,
      the activity of a calcium-sensitive potassium channel in rat visceral-sensory
      neurons which has been suggested to be involved in sensory neuron excitability.
      Single-channel recordings in the inside-out configuration identified a 220 pS
      conductance calcium-activated potassium channel (KCa). From a -20 mV holding
      potential, increasing [Ca2+]i from 0.01 microM to 1.0 microM increased the open
      probability of this channel 92% (from 0.12 to 0.23). However, from a +20 mV
      holding potential, increasing [Ca2+]i from 0.01 to 1.0 microM increased the open
      probability by 326% (from 0.15 to 0.64). In addition, this large conductance KCa
      channel was blocked by TEA (1.0 microM) and charybdotoxin (40 microM) when
      applied to the external surface. These results are the first to characterize a
      large conductance KCa channel in the sensory afferent neurons of the rat nodose
      ganglia and should further expand the understanding of the ionic currents
      involved in the regulation of sensory afferent neuronal activity.

PMID- 7515758
TI  - Cellular and substrate adhesion molecules (integrins) and their ligands in
      cerebral amyloid plaques in Alzheimer's disease.
AB  - Integrins belonging to different subfamilies can be identified
      immunohistochemically in cerebral amyloid plaques. Monoclonal antibodies against
      the VLA family beta 1-integrins show staining of the corona of classical amyloid
      plaques for beta 1, alpha 3 and alpha 6. Immunostaining reveal also the presence
      of collagen and laminin in the corona. Activated microglial cells in classical
      plaques strongly express receptors belonging to the LeuCAM family (beta 2
      integrins). The ligands ICAM and activated complement C3 are found in both
      amorphous and classical plaques. Vitronectin receptor (alpha v) is found in glial
      cells in classical plaques but its ligand vitronectin is seen in both amorphous
      and classical plaques. The data presented here demonstrate the presence of
      different cellular and substrate adhesive molecules (integrins) and their ligands
      in classical plaques. The findings suggest that amyloid plaques show signs of
      regeneration and tissue remodelling.

PMID- 7515765
TI  - Epidermal growth factor suppresses insulin-like growth factor binding protein 3
      levels in human papillomavirus type 16-immortalized cervical epithelial cells and
      thereby potentiates the effects of insulin-like growth factor 1.
AB  - Human ectocervical epithelial cells are a primary target for infection by
      oncogenic papillomaviruses, which are strongly implicated as causative agents in
      the genesis of cervical cancer. Growth factors have been implicated as agents
      that stimulate proliferation and enhance the possibility of malignant
      transformation. In the present study we utilize several human papillomavirus
      (HPV) type 16-immortalized ectocervical epithelial cell lines to investigate the
      effects of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I)
      on cell proliferation and the production of IGF binding proteins (IGFBPs). ECE16
      1 cells, an HPV16-immortalized/nontumorigenic cell line, maintained in defined
      medium, produce and release high levels of IGFBP-3 (38/42 kDa) as well as smaller
      amounts of a 24-kDa IGFBP. Supplementation of defined medium with EGF causes a
      dose-dependent increase in cell growth and a concomitant decrease in the levels
      of IGFBP-3 released into the culture medium. EGF suppression of IGFBP-3 is
      maintained even when EGF-stimulated cell growth is suppressed 67% due to the
      simultaneous presence of 3 ng/ml of TGF beta 1, indicating that EGF suppression
      of IGFBP-3 levels is independent of EGF effects on cell growth. EGF suppression
      of IGFBP-3 production is correlated with a reduction in IGFBP-3 mRNA level. In
      the presence of EGF, the growth response of the cells to ng amounts of IGF-I is
      significantly enhanced. Moreover, the simultaneous presence of both EGF and IGF-I
      reduces the level of IGFBP-3 more efficiently than EGF alone. We also observe
      that the IGFBP-3 level is decreased and the 24-kDa IGFBP level is increased in
      HPV16-positive tumorigenic versus nontumorigenic cell lines. This is the first
      report of EGF acting as a positive regulator of IGF-I action via the IGFBPs. On
      the basis of these findings, we propose that EGF stimulates ECE16-1 cell growth
      via a dual-action mechanism by (a) stimulating growth directly via the EGF
      mitogenic pathway and (b) stimulating growth indirectly by reducing the levels of
      inhibitory IGFBPs and thereby potentiating the effects of IGF-I. In addition, the
      observation that more highly transformed cell types produce lower levels of IGFBP
      3 and higher levels of 24-kDa IGFBP suggests that tumor cells in more advanced
      cervical cancers may have an altered response to IGF-I.

PMID- 7515766
TI  - Protection by galanin against gastric carcinogenesis induced by N-methyl-N'-nitro
      N-nitrosoguanidine in Wistar rats.
AB  - The effects of prolonged administration of the neuropeptide galanin on gastric
      carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, the
      norepinephrine concentration in the gastric wall, and the labeling index of the
      gastric mucosa were investigated in Wistar rats. The rats received 2 or 4
      micrograms/kg body weight of galanin s.c. every other day after 25 weeks oral
      treatment with the carcinogen. Prolonged administration of galanin at 4
      micrograms/kg body weight, but not at 2 micrograms/kg body weight, significantly
      decreased the incidence of gastric cancers in experimental week 52. However, it
      did not influence the histological types of cancers. Galanin at 4 micrograms/kg
      body weight also significantly decreased the labeling index of the antral
      epithelial cells but not the norepinephrine concentration in the gastric wall.
      These findings indicate that galanin inhibits gastric carcinogenesis and suggest
      that its effect may be related to the suppression of proliferation of the antral
      epithelial cells.

PMID- 7515764
TI  - Uterotrophic actions of estradiol and tamoxifen are associated with inhibition of
      uterine insulin-like growth factor binding protein 3 gene expression.
AB  - We have recently shown that uterine insulin-like growth factor I (IGF-I) gene
      expression is up-regulated by tamoxifen, a uterotrophic partial antagonist to the
      estrogen receptor, but down-regulated by the complete estrogen receptor
      antagonist ICI 182780, which causes uterine involution. This result is consistent
      with prior reports indicating that the uterotrophic effects of estradiol are
      mediated at least in part by estradiol-stimulated uterine IGF-I gene expression.
      We demonstrate here that the uterotrophic agents estradiol and tamoxifen each
      suppress expression of the IGF binding protein 3 (IGFBP-3) gene in uterus to less
      than one-third of control values, while oophorectomy or administration of the
      complete estrogen receptor antagonist ICI 182780, both of which result in uterine
      involution, are associated with a greater than 3-fold stimulation of uterine
      IGFBP-3 gene expression. The data reveal a negative correlation between uterine
      weight and uterine IGFBP-3 gene expression as well as reciprocal regulation by
      estradiol of expression in uterus of the genes encoding IGF-I and IGFBP-3. In
      vitro, IGFBP-3 protein accumulation in media conditioned by primary uterine
      cultures was decreased by estradiol treatment and increased by ICI 182780
      treatment. Together, these observations provide a novel mechanism by which
      estradiol and antiestrogens modulate uterine IGF-I physiology that is consistent
      with the view that the mitogenic activity of IGF-I is reduced in the presence of
      IGFBP-3. The uterotrophic toxicity of chronic estradiol or tamoxifen treatment
      may be causally related to both the inhibition of uterine IGFBP-3 expression and
      the stimulation of uterine IGF-I expression by these compounds.

PMID- 7515767
TI  - Involvement of very late activation antigen 4 (VLA-4) and vascular cell adhesion
      molecule 1 (VCAM-1) in tumor necrosis factor alpha enhancement of experimental
      metastasis.
AB  - In this study, we examined the effect of tumor necrosis factor alpha (TNF-alpha)
      on pulmonary metastasis of murine melanoma B16-BL6 by focusing on the
      intercellular adhesion molecules involved in the metastatic process. TNF-alpha
      administration before B16-BL6 inoculation significantly enhanced the experimental
      pulmonary metastasis. The enhancement was seen when TNF-alpha was administered 4
      h, but not 24 h, before B16-BL6 inoculation. Administration of 50-5000 units of
      TNF-alpha increased the number of metastatic lung colonies in a dose-dependent
      manner. Flow cytometric analysis demonstrated a high expression of very late
      activation antigen 4 (VLA-4) on the surface of B16-BL6 cells. Immunoperoxidase
      staining demonstrated that a ligand for VLA-4, vascular cell adhesion molecule 1,
      was expressed on lung vascular endothelium 4 h after administration of TNF-alpha.
      Pretreatment of B16-BL6 cells with an anti-VLA-4 monoclonal antibody abolished
      the TNF-alpha-enhanced pulmonary lung colonies. Administration of an anti
      vascular cell adhesion molecule 1 monoclonal antibody also abolished the
      enhancement. These results indicate that the interaction between VLA-4 on tumor
      cells and vascular cell adhesion molecule 1 on activated endothelial cells is
      critically involved in TNF-alpha enhancement of metastasis.

PMID- 7515768
TI  - Allelic loss in locally metastatic, multisampled prostate cancer.
AB  - In order to determine whether retention or loss of potential tumor suppressor
      loci that map to 8p, 10q, or 16q reflect genetic relationships among prostatic
      intraepithelial neoplasias (PINs), multicentric primary prostatic cancers, and
      regional lymph node metastases or are associated with the metastatic phenotype,
      we analyzed 19 cases of locally metastatic prostate carcinoma (stage D1)
      utilizing polymerase chain reaction techniques. In each case, tissue samples from
      metastatic tumor, the (dominant) primary tumor, and nonneoplastic prostatic
      tissue were examined. In selected cases, allelic loss in additional tumor foci,
      separate from the dominant tumor nodule, and areas of PIN were examined. Allelic
      loss of sequences on 8p, 10q, and 16q were observed in 20-29% of PINs, 18-42% of
      primary tumors, and 8-25% of metastatic tumors. Discrepancies in sequence dosage
      between histological components were most pronounced for 8p sequences, especially
      between the dominant tumor nodule and metastatic deposits in cases in which > or
      = 3 separate tumor foci/gland were identified. These results suggest that
      putative premalignant lesions, moderately or poorly differentiated,
      geographically separate primary tumor foci, and metastases within morphologically
      "complex" prostates (those with > or = 3 foci/gland) are likely to be more
      discordant for sequence dosage at 8p than those within "simpler" glands (< 3
      foci/gland). Also, our results suggest that lymph node metastases may be
      genetically related to either the dominant or additional primary tumor foci in
      more complex prostates and that accumulation of genetic aberration may differ in
      primary and metastatic lesions.

PMID- 7515769
TI  - Direct and indirect effects of recombinant human granulocyte-colony stimulating
      factor on in vitro colony formation of human bladder cancer cells.
AB  - Although the present experimental use of recombinant human granulocyte-colony
      stimulating factor (rG-CSF) has been proven to alleviate the myelosuppression
      induced by antitumor chemotherapy, it is also believed to stimulate growth of
      some nonhematopoietic tumor cells. We investigated both the direct and indirect
      effects of rG-CSF on in vitro colony formation of human bladder cancer cell lines
      using a modified human tumor clonogenic assay. Peripheral blood mononuclear cells
      (PBMC) were used as feeder cells (a mixture of 5 x 10(4) monocytes/dish and 5 x
      10(5) lymphocytes/dish obtained from healthy donors). Human bladder cancer cell
      lines KK-47, TCCSUP and T24, all derived from human transitional-cell carcinomas,
      were incubated continuously with various concentrations of rG-CSF ranging from
      0.01 ng/ml to 10 ng/ml both with and without PBMC for 7-21 days. The
      concentrations of rG-CSF used were chosen as being in the range of achievable
      serum concentrations in patients treated with rG-CSF. At the end of incubation,
      colonies were counted under an inverted phase-contrast microscope, and an
      increase in the number of colonies in comparison with the control was used to
      evaluate the effects of rG-CSF. Results were expressed as a percentage of
      controls. rG-CSF in the upper layer at concentrations ranging from 0.1 ng/ml to
      10 ng/ml stimulated the colony formation of all the cancer cell lines tested in
      the absence of PBMC in the feeder layer, whereas cells with PBMC in the feeder
      layer were significantly stimulated more than those without PBMC in the feeder
      layer (P < 0.05) up to a certain concentration, which varied from cell line to
      cell line. At higher concentrations of rG-CSF, no further stimulation but, on the
      contrary, a decrease in colony formation was observed in cells with PBMC in the
      feeder layer in all the cell lines tested. Colony formation in KK-47 and T24 cell
      lines was significantly inhibited at 5 ng/ml and/or 10 ng/ml rG-CSF compared with
      cells without PBMC in the feeder layer. Our results suggest that rG-CSF may have
      both direct and indirect stimulatory effects on the growth of human bladder
      cancer cell lines in vitro. The results obtained also raise the possibility of
      adverse effects of rG-CSF in bladder cancer patients whose malignant cells may be
      directly and indirectly stimulated by this factor while it is being used
      clinically to alleviate the myelosuppression induced by antitumor chemotherapy.

PMID- 7515770
TI  - Alteration in lymphocyte phenotype associated with administration of adjuvant
      levamisole and 5-fluorouracil.
AB  - Levamisole (LMS) and 5-fluorouracil (5FU) administered adjuvantly are effective
      in reducing the relapse rate following surgical resection of Duke's stage C colon
      carcinoma. It has been postulated that LMS acts to stimulate the immune system
      and that this is one mechanism through which this drug exerts its antitumor
      effects. In this study, peripheral blood mononuclear cells (PBMC) were analyzed
      in nine patients with surgically resected colon carcinoma prior to initiation of
      adjuvant LMS/5FU and at several subsequent times while patients were on therapy.
      Changes in lymphocyte phenotype and soluble interleukin-2 receptor (sIL-2R)
      between pre-study samples and samples obtained during adjuvant LMS/5FU were
      evaluated. Significant increases were seen in the proportion of PBMC expressing
      natural killer (NK) antigen CD56 (14.7 +/- 2.4% versus 18.1 +/- 2.6%; P < 0.05)
      and surface IL-2R (CD25; 0% versus 0.42 +/- 0.15%; P < 0.05), in sIL-2R (314 +/-
      86 U/ml versus 736 +/- 173 U/ml; P < 0.05), and in the CD4:CD8 ratio (2.34 +/-
      0.93 versus 3.47 +/- 1.23; P < 0.01). A significant decrease in the proportion of
      CD8+ PBMC (24.7 +/- 3.8% versus 18.8 +/- 2.6%; P < 0.01) and total CD8+ PBMC (537
      +/- 118 versus 324 +/- 37; P < 0.01) was seen. The increase in CD56+ cells
      correlated with sIL2R levels (r = 0.46; P < 0.05). No changes were noted for CD3,
      CD4, CD5, CD14, CD16, CD19, CDw49a, or TCR delta. The greatest increase in CD56+
      cells and the smallest reduction in CD8+ cells were seen in the subgroup of
      patients who remained disease-free following adjuvant chemotherapy. This study
      suggests that adjuvant LMS/5FU has significant stimulatory effects on the immune
      system, which correlate with patient outcome and may account at least in part for
      its clinical efficacy.

PMID- 7515771
TI  - A rationale for attached gingiva at the soft-tissue/implant interface: esthetic
      and functional dictates.
AB  - For many years, the ultimate goal of the periodontal/restorative team was to
      provide an environment for crowns that would provide long-term, successful
      results. Two essential goals of periodontal therapy were pocket elimination and
      an adequate zone of keratinized gingiva. The establishment of an adequate zone of
      keratinized gingiva, which is firmly attached to the underlying periosteum and
      osseous tissues, is critical for the long-term functional and esthetic results of
      implant restorative dentistry. Five cases are presented that illustrate the
      clinical management of soft tissue to achieve functional and esthetic zones of
      keratinized gingiva.

PMID- 7515772
TI  - Structure of human rhinovirus 3C protease reveals a trypsin-like polypeptide
      fold, RNA-binding site, and means for cleaving precursor polyprotein.
AB  - The structure of human rhinovirus-14 3C protease (3Cpro) has been determined at
      2.3 A resolution and refined to an R factor of 0.22. This cysteine protease folds
      into two topologically equivalent six-stranded beta barrels and in this sense is
      similar to trypsin-like serine proteases. However, there are differences in the
      lengths and positioning of individual beta strands as well as in loops connecting
      elements of secondary structure. The catalytic residues Cys-146, His-40, and Glu
      71 are positioned as in serine proteases, but the oxyanion hole is moved 1-1.2 A
      away. Residues that bind to the 5' noncoding region of rhinovirus genomic RNA are
      located on the opposite side of the molecule from the active site. Interactions
      between individual 3Cpro molecules in the crystal lattice suggest a model for
      intermolecular proteolytic cleavage of the 3CD polyprotein.

PMID- 7515773
TI  - [The evaluation of the oximetric and Doppler sonographic parameters in patients
      with chronic venous insufficiency. A controlled double-blind clinical study
      versus placebo].
AB  - Twenty four patients suffering from chronic venous insufficiency of the lower
      limbs were treated with sulfo-mucopolysaccharides (SMPS) or placebo in a double
      blind controlled study. At recruitment, and again at 60 and 120 days of ongoing
      treatment, each patient was tested for transcutaneous partial oxygen tension and
      for pressure in the posterior tibial vein and saphena by Doppler sonography.
      Findings were assessed in each case separately for the affected limb versus the
      unaffected, or for the more severely affected versus the contralateral limb in
      patients affected bilaterally. Patients treated with the test product, but not
      those treated with placebo, showed definite reduction of venous pressure in the
      posterior tibial vein and internal saphena of the affected or more severely
      affected limb at 60 days of treatment: namely -35% from basal for the posterior
      tibial vein and -28% for the internal saphena. Again on the affected or more
      severely affected side, patients treated with SMPS showed improved transcutaneous
      oxygen tension amounting to +13.8% from basal at 60 days, as opposed to worsening
      condition in the placebo group.

PMID- 7515774
TI  - Neuropsychologic issues in children with disabilities.

PMID- 7515776
TI  - Group II phospholipase A2 in serum in critically ill surgical patients.
AB  - OBJECTIVE: To study the association of increased serum group II phospholipase A2
      concentrations to C-reactive protein concentrations in the sera of critically ill
      surgical patients. DESIGN: Prospective study. SETTING: Surgical intensive care
      unit (ICU) of a university hospital. PATIENTS: Sixty-seven consecutive patients
      admitted to the surgical ICU. INTERVENTIONS: The catalytic activity of
      phospholipase A2 and the serum concentrations of group II phospholipase A2 and C
      reactive protein were measured daily during each patient's stay in the ICU. A
      total of 205 blood samples were taken. In addition, the preoperative serum levels
      of group II phospholipase A2 were determined in patients admitted for cardiac
      surgery. MEASUREMENTS AND MAIN RESULTS: Serum group II phospholipase A2 values
      correlated statistically significantly with the catalytic activity of
      phospholipase A2 and serum C-reactive protein values. In particular, severe
      infections, diseases involving tissue destruction, and elective operations per
      se, caused considerable increases in serum group II phospholipase A2
      concentrations. CONCLUSION: Our results support the earlier presented idea that
      group II phospholipase A2 is an acute-phase reactant.

PMID- 7515777
TI  - Pattern of failure and survival in endobronchial laser resection. A matched pair
      study.
AB  - To evaluate the influence of endobronchial laser resection on survival and the
      pattern of failure in patients with bronchial malignancies, we investigated 75
      patients prospectively. These patients had radiation therapy (mean external dose,
      53.1 Gy) and endobronchial laser resection to treat an inoperable or recurrent
      bronchial carcinoma occluding a major airway. Complete recanalization was
      achieved in 36 percent, partial recanalization was achieved in 51 percent, and no
      recanalization was achieved in 13 percent. These 75 patients were matched
      retrospectively with a group of 75 patients who received external radiation
      therapy because of the same indications, but because of endobronchial compression
      of a major airway by the tumor, received no laser resection. The patients were
      matched for age, sex, TNM-status, histologic features, external radiation dose
      and fractionation, lung resection, cytotoxic therapy, and brachytherapy; they
      were treated in the same period. The incidence of terminal hemorrhage was four
      times higher in patients who received endobronchial laser resection (34.5
      percent) compared with those who did not (7.7 percent). Successful laser
      reopening of a major airway influenced the pattern of failure: with full
      recanalization the cause of death in 23.3 percent of cases was respiratory
      failure and in 26.7 percent, terminal hemorrhage; whereas with no recanalization
      these figures were 56.3 percent and 18.8 percent, respectively. Laser resection
      did not influence overall survival, but in patients with full reopening of a
      bronchus, the time interval from treatment to death was prolonged by more than 4
      months compared with those patients in whom recanalization failed. Comparing our
      observations on the immediate cause of death with reports in the literature, we
      conclude that the higher percentage of terminal hemorrhage in patients receiving
      endobronchial laser resection is not directly related to the treatment, but
      reflects different patterns of tumor growth with respect to mucosal destruction
      not covered by the TNM system.

PMID- 7515778
TI  - Pseudomonas cepacia empyema necessitatis after lung transplantation in two
      patients with cystic fibrosis.
AB  - Lung transplantation is an accepted modality for patients with cystic fibrosis
      (CF) who have end-stage respiratory failure. The postoperative course of these
      patients is often complicated by serious infections with organisms such as
      Pseudomonas aeruginosa and Pseudomonas cepacia that may be multiply resistant to
      conventional antimicrobial agents. We describe two patients with CF who, after
      double lung transplantation, developed the unusual complication of empyema and
      empyema necessitatis due to P cepacia that was resistant to all tested
      antibiotics.

PMID- 7515775
TI  - Morphing as a means of generating variation in visual medical teaching materials.
AB  - In computer-based medical education, there is frequently a need to present
      students with pictorial data representative of the natural variation associated
      with disease presentations as well as the progression of disease within an
      individual. Because of the difficulty in acquiring such data, image acquisition
      is often the most resource-intensive phase of multimedia courseware development.
      In light of the resource demands associated with image content, many courseware
      designers do not make opportune use of image data, but rely instead upon text
      descriptions to provide variation in content. The resulting lack of adequate
      pictorial content often lessens the overall impact of the courseware. To overcome
      constraints imposed by the difficulty in acquiring pictorial content of
      sufficient richness, a methodology of generating variation in visual teaching
      materials has been developed through the use of morphing. These techniques have
      general applicability in creating variation in pictorial teaching materials in a
      variety of image-intensive domains.

PMID- 7515780
TI  - Talc slurry for pleurodesis.

PMID- 7515779
TI  - Multiple pulmonary nodules manifested in a patient with NK cell granular
      lymphocyte proliferative disorder.
AB  - An 18-year-old man was admitted to our hospital with high temperature and
      dyspnea. A chest radiograph revealed the presence of multiple round nodules
      compatible with a metastatic lung cancer. The peripheral white blood cell count
      was 22,000/mm3 and more than 85 percent were atypical large lymphocytes with
      azurophilic granules. He was diagnosed as having natural killer (NK)-cell
      granular lymphocyte proliferative disorder (NK-GLPD) as the lymphocytes were
      positive with CD56, a cell surface marker characteristic for NK cells. The major
      pathologic finding of the tissue collected from the pulmonary nodules by
      transbronchial lung biopsy was infiltration of mostly large granular lymphocytes.

PMID- 7515783
TI  - Human reflexes and late responses. Report of an IFCN committee.

PMID- 7515782
TI  - Effect of antibiotics on Bordetella pertussis adhering activity: hypothesis
      regarding mechanism of action.
AB  - Microbial adherence to epithelial cell surfaces has been implicated as the first
      step in the initiation of several infectious diseases. The ability of antibiotics
      to affect the properties of bacterial adherence to cell surfaces may be a
      criterion in selecting antibiotics for therapy. This study was performed in order
      to investigate the activity of amoxicillin, chloramphenicol, and clarithromycin
      in modifying the adhering activity of Bordetella pertussis to human epithelial
      cells. The actions of antibiotics, alone or combined with aprotinin, were
      compared with that of trypsin, aprotinin and trypsin+aprotinin, to investigate
      the chemical nature of the ligand where antibiotics could act. The adhering
      activity was evaluated on human epithelial cells, collected from the oral mucosa,
      challenged with B. pertussis A2963 previously incubated in the presence of the
      tested substances for 1 h at 37 degrees C in a shaker incubator. After staining,
      the percentage of mucosal cells with more than 50 adhering bacteria was
      evaluated. Under the described experimental conditions, trypsin significantly
      reduced the adherence of B. pertussis. Aprotinin had no effect but was able to
      counteract the inhibitory action of trypsin. Both clarithromycin and
      chloramphenicol markedly reduced adhering activity and their actions were not
      counteracted by aprotinin. Amoxicillin was without effect. It was hypothesized
      that chloramphenicol and clarithromycin, exerting their antimicrobial action by
      inhibiting bacterial protein synthesis, affected bacterial adhesion through an
      unknown mechanism without proteolytic effect.

PMID- 7515784
TI  - Central EMG and tests of motor control. Report of an IFCN committee.

PMID- 7515785
TI  - Periodic synchronous discharges and visual evoked potentials in Creutzfeldt-Jakob
      disease: PSD-triggered flash VEPs.
AB  - We have developed the technique of flash visual evoked potentials (VEPs)
      triggered by periodic synchronous discharges (PSDs) to investigate the
      interaction between PSDs and VEPs in 3 patients with Creutzfeldt-Jakob disease
      (CJD). This technique enables us to explore the cerebral pathophysiology
      underlying CJD. Unexpectedly, we found that PSDs and VEPs did not interact even
      when VEPs were evoked in close temporal proximity to PSDs. Thus, it appears that
      PSDs are generated by a different neuronal mechanism from that involved in VEP
      generation.

PMID- 7515781
TI  - Anti-HIV activity of dideoxynucleosides, foscarnet and fusidic acid is
      potentiated by human leukocyte interferon in blood-derived macrophages.
AB  - Blood-derived macrophages were acutely infected with HIV and treated with a
      combination of leucocyte interferon (IFN) and five anti-HIV drugs. HIV growth was
      assayed by quantitation of p24 antigen in the supernatant and in some experiments
      by determination of reverse transcriptase activity. Both IFN and all drugs, with
      the exception of fusidic acid, inhibited HIV growth in a dose-dependent manner.
      IFN in combination with zidovudine, dideoxycytidine or fusidic acid exerted a
      synergistic effect on HIV titers, while IFN combined with dideoxyinosine or
      foscarnet had an additive effect.

PMID- 7515786
TI  - Evaluation of a computerized system for recognition of epileptic activity during
      long-term EEG recording.
AB  - A new method of recognition of epileptic activity using adaptive segmentation in
      EEG during long-term intensive monitoring was developed in Tampere. The
      performance of the system was validated and compared to the commercially
      available discharge recognition system of Gotman. Twelve approximately 30 min EEG
      segments recorded during intensive monitoring from 6 patients were analysed. On
      these EEG segments two EEG specialists marked the occurrence of epileptic
      activity independently. Later they re-evaluated any differences in their scoring.
      This consensus file was used as a reference in validating the performance of the
      two computer programs. We found that the program developed in Tampere detected
      discharge activity more often than the Gotman system. Both systems performed
      poorly in spike recognition. In the specificity of the recognized segments, the
      Gotman system was better.

PMID- 7515788
TI  - Reversibility of brain-stem evoked potential abnormalities in abstinent chronic
      alcoholics: one year follow-up.
AB  - Brain-stem auditory evoked potentials (BAEPs) were studied in 34 chronic
      alcoholics who had been abstinent for 1 year, and in age- and sex-matched control
      subjects. The patients were examined 3 times, at 1 month, 5 months and 1 year
      after the start of the abstinence treatment. At 1 month of abstinence the
      alcoholics showed differences with respect to controls in the peak V latency (P <
      0.01), and in the III-V (P < 0.01) and I-V (P < 0.01) intervals. After 1 year of
      abstinence a significant improvement in the V (P < 0.01), III-V (P < 0.01) and I
      V (P < 0.01) parameters was recorded. The most notable development was in the 5
      12 month period, with shortening in V latency (P < 0.01) and in the I-V interval
      (P < 0.01); in the first 5 months there was only shortening in the III-V interval
      (P < 0.01). This improvement was also indicated by a decrease in the number of
      patients with BAEP parameter abnormalities. The recovery of the functions
      impaired by chronic alcohol consumption after 1 year of abstinence was
      incomplete, although the tendency was towards normalization.

PMID- 7515787
TI  - Multichannel EEG-based brain-computer communication.
AB  - Individuals who are paralyzed or have other severe movement disorders often need
      alternative means for communicating with and controlling their environments. In
      this study, human subjects learned to use two channels of bipolar EEG activity to
      control 2-dimensional movement of a cursor on a computer screen. Amplitudes of 8
      12 Hz activity in the EEG recorded from the scalp across right and left central
      sulci were determined by fast Fourier transform and combined to control vertical
      and horizontal cursor movements simultaneously. This independent control of two
      separate EEG channels cannot be attributed to a non-specific change in brain
      activity and appeared to be specific to the mu rhythm frequency range. With
      further development, multichannel EEG-based communication may prove of
      significant value to those with severe motor disabilities.

PMID- 7515789
TI  - Differentiation between finger, toe and tongue movement in man based on 40 Hz
      EEG.
AB  - Movements of right and left index fingers, right toe and tongue were studied by
      EEG measurement in the alpha and gamma (30-40 Hz) bands. The EEG was recorded
      with a 56-electrode array over pre- and postcentral areas. For each movement the
      average power decrease, as a measurement of the event-related desynchronization
      or power increase in narrow frequency bands, was calculated. Single-trial data
      from 8 electrodes, 3 frequency bands and 4 time points within a 1 sec window were
      subject to a classification task. It was found that, based on single EEG trials,
      the data from the 4 movements could be differentiated with an accuracy of 70%
      when alpha and gamma band activity were used but only with 58% in the case of the
      alpha band activity alone. This shows that the gamma band activity or 40 Hz EEG
      is strongly related to planning of a specific movement and therefore, improves
      the accuracy of classification significantly.

PMID- 7515790
TI  - Dynamics of event-related potentials to trains of light and dark flashes:
      responses to missing and extra stimuli in elasmobranch fish.
AB  - To characterize the dependencies of event-related potentials (ERPs) in lower
      vertebrates and brain levels upon recent history and sequences of stimuli, trains
      of flashes were delivered at various frequencies to unanesthetized rays while
      recording in optic tectum and telencephalon. ERPs to repetitive stimuli cannot be
      understood in terms of simple refractoriness and recovery. Processes must be
      invoked such as simultaneous excitation and suppression, facilitation and its
      opposite, rebound and induced rhythms, each with development and decay times and
      non-linearities. Some of these processes are uncovered by omitting a stimulus
      from a train. Omitted stimulus potentials (OSPs) act as though the brain expects
      a stimulus within 5-7 msec of the interstimulus interval (ISI) of the train. Very
      few ISIs suffice. The effect upon visual evoked potential (VEP) form and duration
      of the number of stimuli in short trains, before the steady state response (SSR)
      is established, is complex. Alternation of the amplitude of successive VEPs (1
      large every 2 VEPs, 1 in 3, 1 in 4) is one indication of complexities in the SSR.
      OSPs also alternate. A single extra stimulus interpolated into a regular train
      causes distinct effects according to its position. Sharp discontinuities in these
      effects appear with < 5 msec shifts. Total power of the SSR decreases with
      stimulation frequency but there is a large peak of increased power at 7 Hz and
      another at 12 Hz. Induced rhythms are a labile, late phase of OSPs as well as of
      rested VEPs and of the off response to a long light pulse. Jittered ISI
      experiments show that the apparent expectation of the OSP is little affected and
      that the intervals in the last few hundred milliseconds are most influential. The
      OSP studied here (ISI < 0.5 s) is quite different from that so far studied in
      human subjects (ISI > 1 sec). We predict further similarities when each taxon is
      tested in the other ISI range. A major category of response characteristics,
      besides sensitivity, receptive fields and recovery times, is dependence upon
      recent history of iterative events, including intervals, delays omissions and
      perhaps multiple facilitating and forgetting time constants. The variables
      examined parametrically in this study are only some of those available. Such
      dynamical characteristics are important neglected properties of afferent systems
      at each level.

PMID- 7515794
TI  - Quantitative EMG analysis of anticipatory postural adjustments of voluntary
      contraction of leg muscles in standing man.
AB  - The present experiment was undertaken to investigate the sequence of postural
      muscle activities involved in rapidly standing on the toes from a variety of
      standing positions. By varying the angle of incline of the platform on which the
      subject was standing, it was possible to study changes in the adaptability of the
      anticipatory postural muscle activity. Results showed that the initial
      inclination of the platform had a significant effect on the duration of soleus
      muscle activity and the onset and duration of tibialis anterior muscle activity.
      It appears that preparatory and focal motor activity can be modulated in an
      adaptive way according to the change in movement mechanics resulting from
      standing on an inclined platform.

PMID- 7515795
TI  - The effects of signal conditioning on the statistical analyses of gait EMG.
AB  - Ensemble averaged EMG profiles generated for leg muscles during gait have been
      used to clinically assess disease or injury. Several of the methods that have
      been reported for conditioning gait EMG signals were compared using data
      collected from clinically normal subjects walking on a treadmill. Specifically
      investigated were the effects of filtering and the quantity of data averaged upon
      several statistical tests that measure the variability of, or differences
      between, EMG profiles. Our results suggest that the variance ratio (VR) provides
      a reasonable test of data variability because of its modest sensitivity to both
      the degree of filtering and the amount of data averaged. They also suggest that
      of the comparison statistics: Pearson's r, the Kolmogorov-Smirnov T test and the
      ANOVA F ratio, the T test was the most reliable in detecting differences between
      given profiles for all test conditions. However, recognition of this ability of
      the T test must be tempered by the knowledge that while obvious EMG signal
      differences did exist, observable functional differences in gait did not. The
      relationship between statistically similar/dissimilar EMG patterns and clinically
      functional/dysfunctional gait patterns needs to be established. In addition,
      since all of the test statistics studied were affected to some degree by
      filtering and averaging, care should be used when comparing statistical results
      from separate studies unless it is known that the studies were conducted under
      similar conditions, including data processing. To that end, we recommend that at
      least 20 strides be used in the averaging process since the statistics we tested
      have reached or are asymptotically approaching their final values by this point.

PMID- 7515792
TI  - Early detection of distal symmetrical polyneuropathy during HIV infection by
      paired stimulation of sural nerve.
AB  - In 203 HIV infected patients in various clinical stages neurological examination,
      paired stimulation (LPSS), nerve conduction velocity (NCVS) and amplitude (AMPS)
      of the sural nerve, distal latency (DLP), nerve conduction velocity (NCVP),
      amplitude (AMPP) and F waves of the peroneal nerve were recorded. Neurological
      examination revealed symptoms and clinical signs of polyneuropathy in 67 (33%)
      (WR 1-6) of the patients. LPSS after paired stimulation was abnormal in 25.5%,
      NCVS in 14.2%, AMPS in 9.8%, NCVP in 11.8%, DLP in 11.2%, AMPP in 5.9% and FWP in
      14.6%. Our findings indicate a high incidence of peripheral nerve system
      involvement during HIV infection. In 11.5% of all patients only LPSS proved
      polyneuropathy. Neurophysiological results from HIV infected patients with
      symptoms and clinical signs of polyneuropathy were statistically significantly
      different from HIV infected patients without symptoms and clinical signs of
      polyneuropathy. The delay of LPSS represents the most sensitive
      neurophysiological indicator of polyneuropathy during HIV infection and announces
      the onset of peripheral nerve disease even in early stages of infection,
      according to Walter Reed staging classification 1 and 2 (approx. 20%).

PMID- 7515793
TI  - Quantitative surface EMG of pericranial muscles. Relation to age and sex in a
      general population.
AB  - Quantitative EMG levels in pericranial muscles were studied in 547 subjects
      randomly selected from the general population aged 25-64 years. Surface EMGs of
      the right frontal and both temporal muscles were examined during rest and maximal
      voluntary contraction by a blind, standardized method. The amplitude of the EMG
      was expressed as the root mean square and mean rectified voltage. The power
      spectrum was calculated and the mean and median frequencies were extracted.
      During rest no significant differences were found between amplitude levels of the
      temporal muscles, while higher frequency levels were detected on the left side.
      Amplitude and frequency levels were higher in the frontal than the temporal
      muscles during rest, but lower during maximal voluntary contraction, probably for
      morphological differences. In the frontal muscle, females had increased
      amplitudes during rest and decreased levels during maximal voluntary contraction
      compared to males, indicating a higher tension at rest and a reduced number
      and/or size of muscle fibers in females. During maximal voluntary contraction a
      highly significant decrease with age was seen in amplitude and frequency in the
      temporal muscles. The present study is the first population study of EMG levels
      in pericranial muscles and constitutes the necessary basis for evaluating the EMG
      in tension-type headache.

PMID- 7515791
TI  - Fasciculation potentials in foot and leg muscles of healthy young adults.
AB  - The occurrence of fasciculation potentials (FPs) was studied in healthy subjects
      aged 18-25. In 25 males and 25 females 3 intrinsic foot muscles, the tibialis
      anterior and the gastrocnemius muscles on both sides were monitored with surface
      electrodes for 2 min periods. Only potentials with a peak-to-peak amplitude of at
      least 50 microV were counted. The number of FPs per minute (FPs/min) was
      significantly higher in the abductor hallucis (AH) and significantly lower in the
      tibialis anterior as compared to all other muscles (P < 0.001). Men had
      significantly more FPs in the AH than women (P < 0.05). In all subjects FPs were
      found in at least 1 AH. Cooling of the foot did not influence the numbers of
      FPs/min in the foot muscles. To study diurnal variation, all 5 muscles on both
      sides were monitored 3 times/day on 10 different days in another 10 subjects (5
      males, 5 females). Only in the tibialis anterior did the number of FPs never
      exceed 3/min. In the other muscles considerable fluctuations were found,
      especially in the AH, where more than 100 FPs/min were occasionally recorded. In
      the course of the day a significant (P = 0.05) decrease in FPs/min was found for
      the AH muscle. In 8 subjects there was a significant correlation between the
      numbers of FPs in the left and right AH during successive recordings. This
      indicates that an, as yet unknown, general factor determines the fluctuations in
      numbers of FPs.

PMID- 7515796
TI  - Normalization of soleus H-reflex recruitment curves in controls and a population
      of spastic patients.
AB  - We examined soleus H-reflex recruitment in 30 controls and 33 patients with
      spinal cord lesions and spastic spinal paresis. H-reflex gain and threshold were
      determined from recruitment curves after normalization of stimulus intensity as a
      multiple of the current for a threshold M-response. Reflex gain was expressed as
      the mean slope of the H-reflex recruitment curve up to the half-maximal response
      size. Up to this point the curve follows an almost linear trajectory and will
      mainly reflect Ia afferent stimulation. This slope had a large variability but
      was clearly correlated with the H/M ratio. The mean gain was equal in controls
      and patients. The relation between H- and M-thresholds was expressed as a ratio
      which had a lower mean value in the patients. Though both H- and M-thresholds may
      be influenced by peripheral factors, this lower ratio suggests an increase in
      spinal motoneuron excitability in patients.

PMID- 7515797
TI  - Neural modulation of muscle contractile properties during fatigue: afferent
      feedback dependence.
AB  - H reflex amplitudes, an indirect measure of the excitability of the alpha
      motoneuron pool, were recorded from 10 males during fatigue induced by
      submaximal, isotonic, voluntary contractions of the soleus muscle. H reflex
      changes were correlated with electromyographic changes (mean power frequency
      (MPF); root mean square (rms EMG)), under ischemic and non-ischemic conditions.
      The purpose of the ischemia was to block transmission of Ia and possibly Ib
      afferents to assess whether changes in sensory feedback had any effect on alpha
      motoneuron and EMG activity during fatigue. Significant interactions were found
      between ischemic and non-ischemic conditions. After an initial decrease (1.21 +/-
      0.56 mV to 0.54 +/- 0.39 mV), H reflex amplitudes increased during non-ischemic
      trials (0.54 +/- 0.39 mV to 1.13 +/- 0.84 mV). Under ischemic conditions H reflex
      amplitudes decreased (2.11 +/- 1.10 mV to 0.70 +/- 0.74 mV; P < 0.003). During
      non-ischemic conditions, MPF decreased across 5 consecutive trials (157.7 +/-
      17.9 Hz to 124.7 +/- 17.2 Hz), as compared to an increase under ischemic
      conditions (132.8 +/- 21.2 Hz to 197.1 +/- 53.6 Hz; P < 0.001). Root mean square
      amplitude decreased during the non-ischemic trials (31.07 +/- 14.62 mV to 25.98
      +/- 8.26 mV). A greater decrease was noted during the ischemic trials (34.00 +/-
      23.61 mV to 4.95 +/- 3.77 mV; P < 0.001). Data suggest that the CNS modulates
      muscle contraction in order to preserve force output and neuromuscular
      transmission during fatigue. This modulation appears dependent on Ia and/or Ib
      afferent feedback.

PMID- 7515798
TI  - Relationship between force and electromyographic activity during rapid isometric
      contraction in power grip.
AB  - Force response and surface electromyographic (EMG) activity of extrinsic
      extensors and flexors of the hand were measured under 6 target force conditions
      during rapid pulse isometric contractions (power grip) targeted using an
      oscilloscope display of exerted and target forces. For target forces ranging from
      16.7% to 50% of maximum voluntary contraction (MVC), the rate of force rise
      increased with the peak force, while the time to peak force remained almost
      constant. However, at target forces between 66.7% and 100.0% MVC, the rate of
      force rise leveled off and the time to peak force was prolonged. In association
      with these changes in force trajectories, modulation of the EMG activity of the
      flexor digitorum superficialis muscle was observed. At the lowest target force
      (16.7 MVC), the EMG of this muscle showed a single initial activity; the activity
      increased linearly up to the 50% MVC target force, while the duration was
      relatively constant. However, at target forces above 50% MVC, no further increase
      of the initial activity was observed, while the amplitude and duration of an
      additional activity progressively increased. These results indicate that the
      neural control of rapid isometric contraction at target forces at and below 50%
      MVC differs from that operating at larger target force levels.

PMID- 7515799
TI  - Motor cortex inhibition in patients with ataxia.
AB  - We studied the effects of a subthreshold magnetic stimulus over the motor cortex
      and an electrical stimulus over the cerebellum on EMG responses produced by a
      suprathreshold magnetic stimulus over the motor cortex. In normal subjects, both
      subthreshold conditioning stimuli and cerebellar stimuli could suppress responses
      to suprathreshold magnetic test stimuli when given at appropriate timings:
      "cortico-cortical" and "cerebellar" inhibition, respectively. In all patients
      with degenerative ataxias and patients with a lesion in the cerebellar thalamus,
      the "cortico-cortical" inhibition was normal and the "cerebellar" inhibition was
      absent. We conclude that cerebellar systems make no or little contribution to the
      above-mentioned "cortico-cortical" inhibition.

PMID- 7515800
TI  - Differentiation of sensorimotor neuronal structures responsible for induction of
      motor evoked potentials, attenuation in detection of somatosensory stimuli, and
      induction of sensation of movement by mapping of optimal current directions.
AB  - Transcranial magnetic stimulation (TMS) of the sensorimotor cortex can evoke
      motor evoked potentials (MEPs), attenuation in detection of somatosensory stimuli
      (ADSS), and sensation of movement (SOM) referred to the same body part. In this
      study we tried to differentiate the substrates responsible for these effects. In
      6 normal volunteers, TMS was applied with a nearly monopolar Dantec stimulator
      and a butterfly coil. Optimal scalp location and current direction were
      determined for induction of MEPs in abductor pollicis brevis (APB), first dorsal
      interosseous (FDI), and adductor digiti minimi (ADM); SOM in digits 2 and 5 in an
      ischemically paralyzed hand; and ADSS applied to digits 2 and 5. All 3 muscles'
      MEPs and SOM and ADSS in both digits were optimally activated from a single scalp
      position. In all subjects, optimal current directions for MEPs pointed
      anteriorly; those for ADSS and SOM pointed posteriorly. Optimal current
      directions showed the same progression in all subjects for MEPs (ADM, FDI, and
      APB from antero-lateral to antero-medial), ADSS (digit 5 postero-medial, 2
      postero-lateral), and SOM (digit 1 through 5 postero-lateral to postero-medial).
      We conclude that neuronal networks targeting corticospinal neurons responsible
      for MEPs are different from those leading to SOM and ADSS (which could not be
      differentiated).

PMID- 7515801
TI  - A new method to determine pudendal nerve motor latency and central motor
      conduction time to the external anal sphincter.
AB  - By placing the earth electrode between the site of the stimulus and the site of
      derivation, peripheral motor latency to the external anal sphincter can be
      determined and thus central motor conduction time (CMCT) can be calculated. In 18
      volunteers we found a total motor conduction time of 19.4 msec (S.D. 1.71) after
      stimulation of the motor cortex and recording above the external anal sphincter.
      Latency was 5.6 msec (S.D. 0.66) when stimulated above L1 and pudendal latency
      (MEPuL) after stimulation above S3 was 2.5 msec (S.D. 0.32). CMCT to L1 (TMCT
      minus MCT to L1) was 13.8 msec (S.D. 1.13) and to S3 (TMCT minus MEPuL) it was
      16.9 msec (S.D. 1.67). This method allows us to locate spinal dysfunction more
      precisely and also improves diagnosis of a possible neuropathy of the pudendal
      nerve.

PMID- 7515803
TI  - Endoscopic treatment of esophago-gastric tumors.

PMID- 7515802
TI  - Blink reflex far fields mimicking putative cortical trigeminal evoked potentials.
AB  - The R1 component of the blink reflex was evoked by stimulation of the left
      supraorbital and infraorbital nerves in 10 subjects. In addition, an artificial
      dipole was placed over the left eyebrow, in order to simulate the occurrence of
      the R1 component of the blink reflex. These electrical events were recorded at
      scalp locations Fz, F8, F7, C6, C5, referred either to Cv7 (seventh cervical
      vertebra) or to Fz. It was found that the blink R1 and the field of the
      artificial dipole had similar behaviour across the scalp; larger amplitudes were
      recorded ipsilateral to the stimulus from derivations referred to Cv7, but when
      referred to Fz larger contralateral amplitudes were measured. In the latter
      condition, the scalp-recorded R1 shows similar amplitude behaviour to electrical
      events originating from the cortex and hence its appearance may be deceiving.

PMID- 7515805
TI  - Statistics of RNA melting kinetics.
AB  - We present and study the behavior of a simple kinetic model for the melting of
      RNA secondary structures, given that those structures are known. The model is
      then used as a map that assigns structure dependent overall rate constants of
      melting (or refolding) to a sequence. This induces a "landscape" of reaction
      rates, or activation energies, over the space of sequences with fixed length. We
      study the distribution and the correlation structure of these activation
      energies.

PMID- 7515804
TI  - Mechanosensitivity of cell membranes. Ion channels, lipid matrix and
      cytoskeleton.
AB  - Physical and biophysical mechanisms of mechano-sensitivity of cell membranes are
      reviewed. The possible roles of the lipid matrix and of the cytoskeleton in
      membrane mechanoreception are discussed. Techniques for generation of static
      strains and dynamic curvatures of membrane patches are considered. A unified
      model for stress-activated and stress-inactivated ion channels under static
      strains is described. A review of work on stress-sensitive pores in lipid-peptide
      model membranes is presented. The possible role of flexoelectricity in mechano
      electric transduction, e.g. in auditory receptors is discussed. Studies of
      flexoelectricity in model lipid membranes, lipid-peptide membranes and natural
      membranes containing ion channels are reviewed. Finally, possible applications in
      molecular electronics of mechanosensors employing some of the recognized
      principles of mechano-electric transduction in natural membranes are discussed.

PMID- 7515807
TI  - Alpha-subunit and human chorionic gonadotropin-beta immunoreactivity in patients
      with malignant endocrine gastroenteropancreatic tumours.
AB  - In the serum of patients with malignant endocrine gastroenteropancreatic (GEP)
      tumours, both alpha-subunit (alpha-SU), common to all glycoprotein hormones, as
      well as free beta-subunit of human chorionic gonadotropin (hCG-beta) have been
      reported to be elevated in a substantial fraction. Both have been discussed as
      markers of malignancy in these neoplasms. In the present study we evaluated the
      diagnostic significance of alpha-SU and hCG-beta as serum markers in patients
      with malignant endocrine gastroenteropancreatic tumours. The study group
      consisted of 52 patients with endocrine GEP-malignancies (24 nonfunctioning, 23
      carcinoid syndromes, four gastrinoma, one glucagonoma), located in the small
      intestine (n = 29), pancreas (n = 17), colon or rectum (n = 3), retroperitoneum
      (n = 2) and stomach (n = 1). alpha-SU and hCG-beta immunoreactivity was also
      assessed in the serum of patients with benign GEP-tumors (five insulinoma, and
      three gastrinoma). Concentrations of alpha-SU and hCG-beta were determined using
      two highly sensitive and specific immunoradiometric assays employing two
      monoclonal antibodies each. In 19 of 52 patients (37%), either alpha-SU (n = 9),
      hCG-beta (n = 7) or both subunits (n = 3) were elevated. In the subgroup of 24
      patients with nonfunctioning GEP-tumours, increased concentrations of either
      alpha-SU (n = 6) or hCG-beta(n = 3) or both subunits (n = 1) were found in 10 of
      24 patients (42%). In four of 23 patients with carcinoid syndrome (17%), either
      alpha-SU (n = 2), hCG-beta(n = 1) or both subunits (n = 1) were above the normal
      range.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515806
TI  - Toxicological approaches to complex mixtures.
AB  - This paper reviews the role of toxicological studies in understanding the health
      effects of environmental exposures to mixtures. The approach taken is to review
      mixtures that have received the greatest emphasis from toxicology; major mixtures
      research programs; the toxicologist's view of mixtures and approaches to their
      study; and the complementary roles of toxicological, clinical, and
      epidemiological studies. Studies of tobacco smoke, engine exhaust, combustion
      products, and air pollutants comprise most of the past research on mixtures.
      Because of their great experimental control over subjects, exposures, and
      endpoints, toxicologists tend to consider a wider range of toxic interactions
      among mixture components and sequential exposures than is practical for human
      studies. The three fundamental experimental approaches used by toxicologists are
      integrative (studying the mixture as a whole), dissective (dissecting a mixture
      to determine causative constituents), and synthetic (studying interactions
      between agents in simple combinations). Toxicology provides information on
      potential hazards, mechanisms by which mixture constituents interact to cause
      effects, and exposure dose-effect relationships; but extrapolation from
      laboratory data to quantitative human health risks is problematic. Toxicological,
      clinical, and epidemiological approaches are complementary but are seldom
      coordinated. Fostering synergistic interactions among the disciplines in studying
      the risks from mixtures could be advantageous.

PMID- 7515810
TI  - CD5- dendritic epidermal T cells are derived from CD5+ precursor cells.
AB  - Murine Thy-1+, TcR V gamma 3/V delta 1+ dendritic epidermal T cells (DETC) differ
      from most other T cell subsets by the absence of CD4 and CD8 antigens as well as
      the lack of CD5 expression. To see whether negativity for those antigens is an
      intrinsic feature of a given T cell population or if such triple-negative T cells
      go through a maturational stage where they express these antigens, we determined
      the phenotype of TcR V gamma 3+ fetal thymocytes which are the precursor cells of
      DETC. We found that TcR V gamma 3+ fetal thymocytes phenotypically differ from
      mature DETC in that they are CD5+, mostly CD8+ and partly CD4+. The injection of
      fetal thymic suspensions containing TcR V gamma 3+/CD5+ (but not TCR V gamma
      3+/CD5-) thymocytes into Thy-1-disparate athymic nude mice resulted in the
      appearance of donor-type TcR V gamma 3+/CD5- dendritic cells in the recipients'
      epidermis, indicating that TcR V gamma 3+ thymocytes are indeed the precursors of
      CD5- DETC. Tracing CD5 expression on DETC precursors during their intrathymic
      maturation and their migration to the fetal skin, we found that (i) the earliest
      DETC precursor cells as defined by TcR V gamma 3 expression express high levels
      of CD5 antigen (day 15 of gestation), (ii) after day 16 of gestation 70% of TcR V
      gamma 3+ thymocytes express high and 30% express intermediate levels of CD5,
      (iii) TcR V gamma 3+ cells in the fetal blood express low levels of CD5, (iv) the
      first TcR V gamma 3+ cells entering the epidermis express very low levels of this
      antigen and (v) TcR V gamma 3+ epidermal cells later than day 19 of gestation are
      CD5-. A similar down-regulation of CD5 expression on DETC precursors was also
      noted when TcR V gamma 3+ cells were cultured in vitro. Even the addition of PMA
      and ionomycin, which up-regulates CD5 expression on TcR alpha/beta-bearing
      thymocytes and lymph node T cells, could not prevent CD5 down-regulation on DETC
      precursors. The described cell system may serve as a useful tool in further
      experiments aimed to clarify the function of the CD5 glycoprotein as well as the
      mechanism(s) regulating its expression.

PMID- 7515808
TI  - Differential expression of lymphocyte homing receptors by human memory/effector T
      cells in pulmonary versus cutaneous immune effector sites.
AB  - The heterogeneous expression of lymphocyte homing receptors (HR) by the
      (CD45RA(low)/RO(high)) memory/effector T cell population in the human is thought
      to define subsets with tissue-selective recirculatory potential. To investigate
      further the localization characteristics of these T cells, we used multiparameter
      flow cytometry to quantitate T cell subsets defined by expression of the skin
      selective HR called the cutaneous lymphocyte-associated antigen (CLA), the
      peripheral lymph node (PLN) HR L-selectin, the mucosal-associated HR alpha 4 beta
      7-integrin, and the mucosal-associated adhesion molecule alpha e beta 7-integrin
      in either cutaneous or pulmonary immune effector sites and corresponding
      peripheral blood. Compared to peripheral blood, skin T cells were highly enriched
      for the CLA+/L-selectin+/alpha e beta 7-integrin- memory/effector subset, whereas
      lung memory/effector T cells were predominantly CLA-to low L-selectin-, and
      almost half were alpha e beta 7-integrin+. alpha 4 beta 7-integrin expressing
      memory/effector T cells were diminished in both skin and lung, suggesting that
      this HR is not a major participant in determining localization specificity in
      either of these sites. The characteristic pulmonary T cell HR phenotype did not
      significantly differ between the normal subjects and those with pulmonary
      inflammatory disease, and did not correlate with markers of T cell activation.
      Induction of a rapid up-regulation of pulmonary inflammation via intrabronchial
      allergen challenge in asthmatic patients tended to decrease localization
      specificity, resulting in a more general importation of memory/effector subsets.
      Taken together, these results suggest that tissue microenvironments play a major
      role in determining the character of local T cell infiltrates via their ability
      to import and retain memory/effector subsets selectively or, more generally,
      depending on the intensity of local inflammatory stimuli.

PMID- 7515809
TI  - Lipopolysaccharide-induced cytokine production in human monocytes: role of
      tyrosine phosphorylation in transmembrane signal transduction.
AB  - The signal transduction events that follow the binding of lipopolysaccharide
      (LPS) to the macrophage cell surface are not well defined. In the current studies
      LPS was found to induce alterations in phosphorylation of monocyte proteins on
      tyrosine. Herbimycin A and genistein, inhibitors of tyrosine kinases, markedly
      attenuated LPS-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
      (IL-6) protein and mRNA production. Reciprocally, the tyrosine phosphatase
      inhibitor sodium orthovanadate enhanced LPS-induced production of TNF-alpha. LPS
      induced a concentration-dependent increase in tyrosine phosphorylation of several
      proteins, which paralleled and preceded the onset of LPS-induced TNF-alpha
      production. LPS stimulation had different but reproducible effects on three
      members of the src family of tyrosine kinases. Both Hck and Lyn kinase activity
      increased before the onset of TNF-alpha production, consistent with their
      participation in the observed LPS-induced tyrosine phosphoprotein accumulation.
      In contrast, Yes kinase activity was not affected. These observations were made
      at concentrations of LPS that required serum rich in LPS-binding protein and the
      monocyte surface antigen CD14 for TNF-alpha production. These data indicate that
      tyrosine kinases and phosphatases are involved in the signal transduction cascade
      by which LPS induces production of TNF-alpha and IL-6 by human monocytes, and
      suggest that Lyn and Hck are candidate participants in this process.

PMID- 7515811
TI  - Pro-T cells in fetal thymus express c-kit and RAG-2 but do not rearrange the gene
      encoding the T cell receptor beta chain.
AB  - Ten percent of 15-day fetal thymocytes of mice were Pgp-1+Thy-1lo cells. Half
      were strongly stained with monoclonal antibodies (mAb) recognizing the oncogene
      product, c-kit, but were not stained with mAb against non-T cell markers such as
      B220, Mac-1 and Gr-1. The isolated Pgp-1+c-kit+ thymocytes showed no rearranged
      bands for V-DJ and D-J of T cell receptor (TcR) beta, but Pgp-1(-)-c-kit-
      thymocytes showed D-J rearranged bands. Both cells expressed the RAG-2 gene which
      is required for the V(D)J recombination process. When Pgp-1+c-kit+ thymocytes
      were cultured in 2-deoxyguanosine-treated alymphocytic fetal thymus, they became
      TcR-expressing mature type T cells, but this differentiation was reduced by the
      addition of anti c-kit mAb. These data indicate that Pgp-1+c-kit+ thymocytes are
      pro-T cells with the potential to differentiate mature T cells in the thymic
      environment. This study also indicates that c-kit-mediated signals promote the
      differentiation of thymocytes during their early stages.

PMID- 7515812
TI  - Characterization of brain-isolated rat encephalitogenic T cell lines.
AB  - In the present study, we have isolated and characterized five myelin basic
      protein (MBP)-reactive T cell lines directly from the brains of Lewis rats during
      the early paralytic phase of experimental autoimmune encephalomyelitis (EAE).
      Each T cell line responded to the dominant encephalitogenic epitope spanning
      residues 68-88, and did not react against the conserved encephalitogenic epitope
      [MBP(87-99)] or the nonencephalitogenic MBP epitope [MBP(50-69)]. We determined
      the T cell receptor (TcR) beta chain usage by polymerase chain reaction, DNA
      sequencing analysis and by generation of MBP-reactive hybridomas from one of the
      T cell lines (BT74). The results revealed that brain-infiltrating, MBP-reactive T
      cells freshly isolated early in the course of the disease exhibit TcR diversity.

PMID- 7515813
TI  - Signaling through CD50 (ICAM-3) stimulates T lymphocyte binding to human
      umbilical vein endothelial cells and extracellular matrix proteins via an
      increase in beta 1 and beta 2 integrin function.
AB  - Regulated adhesion of T lymphocytes to antigen-presenting cells, endothelial
      cells and extracellular matrix proteins is crucial in T lymphocyte activation and
      migration to the sites of injury. In this study, we show that three monoclonal
      antibodies (mAb) recognizing different epitopes on the CD50 (ICAM-3) molecule
      increase T lymphocyte adhesion to tumor necrosis factor (TNF)-stimulated human
      umbilical vein endothelial cells and extracellular matrix proteins. These
      phenomena are mediated by an increase in beta 1 and beta 2 integrin avidity since
      (a) CD50-induced adhesion to endothelial cells was abrogated by simultaneous
      blocking of beta 1- and beta 2-mediated adhesion pathways but not by interfering
      with either one individually, (b) CD50 mAb increased beta 1 integrin-mediated
      adhesion to extracellular matrix proteins and to fibronectin-derived synthetic
      peptides, (c) CD50 mAb enhanced T lymphocyte binding to ICAM-1 transfectants, and
      (d) CD50 mAb did not modify surface expression patterns of beta 1 or beta 2
      integrins on T lymphocytes. Our data suggest that constitutively expressed CD50
      (ICAM-3) can play a pivotal role in initiating a cascade of adhesion events which
      may be crucial in immune activation and in the development of inflammatory
      lesions.

PMID- 7515814
TI  - Expression of CD5 and CD38 by human CD5- B cells: requirement for special
      stimuli.
AB  - In this study the mode of expression of CD5 by human tonsillar CD5- B cells after
      stimulation with different agents was investigated. Resting B cells were
      separated into CD5+ and CD5- cells and the two cell fractions exposed to phorbol
      12-myristate 13-acetate (PMA). CD5- B cells expressed CD5 and maximum CD5
      expression was achieved after approximately 60 h of culture. Based upon the
      proportions of cells that express CD5 as well as those of the cells surviving in
      culture, it was calculated that 15-25% of the total CD5- B cells were induced to
      express CD5. Unlike CD5- B cells, CD5+ B cells proliferated vigorously in
      response to PMA as assessed by [3H]thymidine incorporation and cell cycle
      analysis in vitro. However, the expression of CD5 by CD5- B cells was not related
      to the selective expansion of some CD5+ B cells left over as contaminant cells
      since this occurred in the absence of cell proliferation. Upon exposure to PMA,
      CD5- B cells remained in the G0-G1 phases of the cell cycle and did not express
      the Ki67 antigen or incorporate [3H]thymidine. Furthermore, mitomycin C treatment
      of the CD5- B cells did not prevent CD5 expression. Phenotypic studies disclosed
      that CD5+ B cells but not CD5- B cells expressed CD39. This finding offered the
      opportunity to carry out an additional control experiment. Separation of the two
      populations according to the expression of CD39 confirmed the finding obtained by
      fractionating the cells into CD5+ and CD5- B cells. The cells induced to express
      CD5 also expressed CD38 that was not detected on resting CD5- B cells. In this
      respect, the CD5- B cells that converted into CD5+ cells (inducible CD5+ B cells)
      resembled the cells from the CD5+ B cell fractions that up-regulated CD5 and also
      expressed CD38 upon exposure to PMA alone. Another example of coordinate
      expression of these two antigens was the finding that exposure to PMA in the
      presence of recombinant interleukin-4 (rIL-4) resulted in inhibition of the
      expression of CD5 and CD38. Although virtually all of the tonsillar CD5- B cells
      expressed the CD69 activation marker, no cells other than those co-expressing CD5
      and CD38 were induced to express CD5 by PMA alone. Resting CD5- B cells failed to
      express CD5 and/or CD38 when cultured with PMA in the presence of EL4 T cells and
      IL-4-free T cell supernatants.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7515815
TI  - Interleukin-10 prevents experimental allergic encephalomyelitis in rats.
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease mediated
      by myelin protein-specific CD4+ T lymphocytes of the T(h)1-like phenotype. In
      rats, the disease is characterized by a monophasic clinical manifestation,
      followed by a subsequent spontaneous remission and the establishment of life-long
      resistance to reinduction of disease. Recent data indicate that intracerebral
      cytokine production, in particular synthesis of interleukin(IL)-10, is
      selectively up-regulated during the recovery phase of disease. This led us to
      assess the effects of IL-10 on different rat lymphoid cell functions in vitro and
      to consider the possibility of an IL-10-mediated treatment to prevent the
      induction of central nervous system (CNS) autoimmune disease in vivo. Human
      recombinant IL-10 suppressed interferon-gamma induced major histocompatibility
      complex class II up-regulation in rat peritoneal macrophages, exhibited
      pleiotropic effects on thymocytes and totally abrogated tumor necrosis factor
      production of encephalitogenic T lymphocytes in vitro, without simultaneously
      affecting proliferative responses of the cells. Upon systemic administration
      during the initiation phase of disease, IL-10 was effective in markedly
      suppressing the subsequent induction of EAE in Lewis rats. This suppression of
      clinical disease coincided with a significant and specific elevation of myelin
      basic protein-specific autoantibody production, a sustained T cell proliferative
      response to myelin basic protein and a diminution of CNS infiltrations and thymic
      involutions in diseased animals. These data implicate IL-10 as a possible
      candidate for treatment of T(h)1-mediated CNS (auto-) immune diseases.

PMID- 7515816
TI  - Induction of a cytotoxic T cell response by co-injection of a T helper peptide
      and a cytotoxic T lymphocyte peptide in incomplete Freund's adjuvant (IFA):
      further enhancement by pre-injection of IFA alone.
AB  - We have previously demonstrated that it is possible to induce a consistent and
      strong cytolytic T lymphocyte (CTL) response to synthetic peptides, corresponding
      to poorly immunogenic malaria CTL epitopes, by co-injecting them with peptides
      representing defined T helper (Th) epitopes in incomplete Freund's adjuvant
      (IFA). In this study we have tested different immunization protocols to improve
      further the elicitation of the CTL response. We show that the CTL response to a
      mixture of Th + CTL peptides administered in IFA was further enhanced by a
      previous injection of the Th epitope peptide in IFA. Moreover, we found that the
      response could be significantly augmented by a pre-injection of IFA alone. This
      enhancement was observed only if the Th epitope was also present in the second
      injection. The number of lymph node cells recovered was 2-3-fold higher in mice
      pre-injected with IFA, but the increase in specific CTL activity, expressed as
      lytic units per animal, by pre-injection of IFA was at least 10-20-fold. Thus,
      pre-injection of IFA clearly increases the magnitude of a subsequent CTL
      response.

PMID- 7515817
TI  - Non-NMDA receptor-mediated regulation of hypothalamic dopaminergic neurons in the
      rat.
AB  - The purpose of the present study was to examine the effects of non-NMDA receptor
      blockade and activation on the activity of tuberoinfundibular dopaminergic
      (TIDA), periventricular-hypophysial dopaminergic (PHDA) and, for comparison,
      nigrostriatal dopaminergic (NSDA) neurons in male and female rats. The activity
      of TIDA, PHDA and NSDA neurons was estimated by measuring the concentration of
      the primary dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the
      median eminence, intermediate lobe of the posterior pituitary and striatum,
      respectively. Systemic administration of the alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA)-selective antagonist 6-nitro-7-sulfamoyl
      benzo[f]quinoxaline-2,3(1H,4H)-dione (NBQX) increased DOPAC concentrations in the
      median eminence and intermediate lobe, and decreased plasma concentrations of
      prolactin and alpha-MSH, in a dose- and time-related manner. In contrast, NBQX
      had no effect on DOPAC concentrations in the striatum, suggesting that non-NMDA
      receptors are not involved in the tonic regulation of NSDA neurons. The increase
      in DOPAC concentrations in the median eminence and intermediate lobe, and the
      decrease in plasma concentrations of prolactin and alpha-MSH, produced by NBQX
      were prevented by AMPA but not by kainic acid. Taken together, the results
      demonstrate that endogenous excitatory amino acid neurotransmitters, acting at
      AMPA receptors, tonically inhibit both TIDA and PHDA neurons, and thereby
      increase the secretion of prolactin and alpha-MSH in male and female rats.

PMID- 7515818
TI  - Thaliporphine, a positive inotropic agent with a negative chronotropic action.
AB  - The effects of thaliporphine on contractions and electrophysiological properties
      of cardiac tissues were examined. In driven rat left atria and right ventricular
      strips, thaliporphine (1-30 microM) increased twitch tension dose-dependently.
      The positive inotropic effect of thaliporphine was unaffected by atenolol (3
      microM) and prazosin (1 microM) but was significantly suppressed by verapamil (1
      microM). An electrophysiological study revealed that thaliporphine (3-10 microM)
      markedly inhibited the action potential upstroke and prolonged the action
      potential duration (APD50) in rat and guinea pig atrial and ventricular cells. At
      1-30 microM, thaliporphine reduced the transient outward current (Ito) of the rat
      ventricular cells in a dose-dependent manner. The peak Ito in rat ventricular
      cells and the delayed rectifying K+ current (Ik in guinea pig ventricular cells
      were reduced by thaliporphine (10 microM) to 37.3 +/- 2.1% (n = 8) and 45.3 +/-
      1.8% (n = 4), respectively. In rat ventricular cells and guinea pig atrial cells,
      thaliporphine (1.5 microM) reduced the Na+ inward current (INa) with a negative
      shift (4-5 mV) relative to its half inactivation potential. For the Ca2+ inward
      current (ICa) in rat ventricular cells, 10 microM of thaliporphine caused a
      smaller increase in the peak ICa than 0.5 microM of Bay K 8644. The increase in
      ICa elicited by both agents was associated with a negative shift of its half
      activation potential from -10 +/- 2 mV to -18 +/- 2 mV (n = 6) by thaliporphine
      and -11 +/- 2 to -19 +/- 2 mV (n = 4) by Bay K 8644. These results indicate that
      thaliporphine is a weak Ca2+ channel agonist with strong Na+ and K+ channel
      blocking activities. The positive inotropic effect may be due to an increase in
      calcium entry mediated via partial activation of calcium channels or by
      inhibition of K+ efflux. Inhibition of K+ efflux would result in prolongation of
      APD50 and contribute to the negative chronotropic effect of thaliporphine.

PMID- 7515819
TI  - Muscarinic M1 and M3 receptor antagonist effects of a new pirenzepine analogue in
      isolated guinea-pig ileal longitudinal muscle-myenteric plexus.
AB  - The new pirenzepine analogue DF 545 has been tested for its muscarinic M1 and M3
      receptor antagonist properties in guinea-pig longitudinal muscle-myenteric plexus
      preparations. McN-A-343-induced inhibition of twitch contractions was taken as a
      parameter for muscarinic M1 receptor activation while electrical and
      acetylcholine-induced contractions were considered as a model for muscarinic M3
      receptor stimulation. An unexpected contractile effect evoked by McN-A-343 was
      also investigated. In contrast to pirenzepine, DF 545 only weakly counteracted
      the M1-mediated McN-A-343 inhibitory effect but blocked M3-related twitch- or
      acetylcholine-stimulated responses with a 2-fold higher affinity than
      pirenzepine. Therefore, in this preparation, our findings suggest that DF 545
      does not share the selectivity profile exhibited by pirenzepine at ileal
      muscarinic receptors. Studies on the McN-A-343 contractile effect provide
      evidence that this agonist may interact with ileal muscarinic effector sites in a
      different way from other cholinergic agents.

PMID- 7515820
TI  - Effects of histamine on 5-hydroxytryptaminergic neuronal activity in the rat
      hypothalamus.
AB  - Effects of pharmacological manipulations which mimic or enhance histaminergic
      neuronal transmission were determined on the activity of 5-hydroxytryptaminergic
      neurons projecting to the hypothalamus of male rats. Intracerebroventricular
      administration of histamine decreased 5-hydroxytryptamine (5-HT) and increased 5
      hydroxyindoleacetic acid (5-HIAA) concentrations in several hypothalamic nuclei;
      these effects were blocked by the histamine H1 receptor antagonist mepyramine but
      not the histamine H2 receptor antagonist zolantidine. Blockade of the 5-HT
      reuptake system by fluoxetine did not prevent histamine-induced decreases in 5-HT
      concentrations suggesting that histamine is not transported into nerve terminals
      via the 5-HT reuptake system to subsequently displace 5-HT stores. These data
      suggest that exogenous histamine increases 5-hydroxytryptaminergic neuronal
      activity through an action at histamine H1 receptors. In contrast, neither the
      histamine H3 receptor antagonist thioperamide, the histamine-N-methyltransferase
      inhibitor metoprine, nor combined thioperamide-metoprine treatment affected
      concentrations of 5-HT or 5-HIAA suggesting these agents, which purportedly
      enhance endogenous histaminergic transmission, do not affect 5
      hydroxytryptaminergic neuronal activity. These results reveal that procedures
      commonly employed to study central actions of histamine differentially affect 5
      hydroxytryptaminergic neuronal activity in the rat hypothalamus.

PMID- 7515821
TI  - delta-9-Tetrahydrocannabinol regulates substance P and enkephalin mRNAs levels in
      the caudate-putamen.
AB  - We have recently localized delta-9-tetrahydrocannabinol (THC) receptor in the
      projecting neurons of the striatum which are known to express the neuropeptides
      substance P and enkephalin. We now report for the first time, by quantitative in
      situ hybridization, that a 3-week treatment with THC significantly increases in
      the adult rat caudate-putamen the messenger RNAs levels for substance P and
      enkephalin. These data indicate that THC may regulate gene expression of
      neuropeptides in the brain.

PMID- 7515822
TI  - Desensitization, phosphorylation and palmitoylation of the human dopamine D1
      receptor.
AB  - The regulation and post-translational modifications of the human dopamine D1
      receptor were studied in the baculovirus-eukaryotic cell expression system.
      Baculovirus constructs containing either the DNA encoding the dopamine D1
      receptor or a DNA encoding a c-myc epitope tagged dopamine D1 receptor (c-myc
      dopamine D1 receptor) were used to infect Spodoptera frugiperda (Sf9) insect
      cells. Expressed dopamine D1 and c-myc-dopamine D1 receptors bound agonists and
      antagonists with affinities and a rank order of potency characteristic of a
      classical dopamine D1 receptor pharmacological profile. In membrane preparations
      from cells expressing c-myc-dopamine D1 receptor, the photoaffinity label
      [125I](3-methyl-2-[4'-azidophenyl]-2,3,5-tetrahydro-2H-3-benzazepine) ([125I]MAB)
      bound specifically upon photolysis. A major broad band of approximately 48 kDa
      was detected. This species was identified in immunoblots by the monoclonal
      antibody raised against the c-myc epitope of c-myc-dopamine D1 receptor was
      isolated by immunoprecipitation from whole cells and was shown to be post
      translationally modified by phosphorylation and palmitoylation. Exposure of cells
      expressing c-myc-dopamine D1 receptor to dopamine for 15 min resulted in a
      reduction in the maximal dopamine stimulated adenylyl cyclase activity, which was
      accompanied by an increased phosphorylation of the receptor and a rapid
      redistribution of surface c-myc-dopamine D1 receptor as detected by in situ
      immunofluorescence. Dopamine exposure also resulted in an increased level of
      incorporation of [3H]palmitic acid into the receptor. Thus, we provide the first
      evidence that the human dopamine D1 receptor undergoes agonist-dependent
      desensitization, phosphorylation and palmitoylation.

PMID- 7515823
TI  - Actions of phenylglycine analogs at subtypes of the metabotropic glutamate
      receptor family.
AB  - The functional effects of phenylglycine analogs on metabotropic glutamate
      receptor (mGluR) subtypes mGluR1 alpha, mGluR2 and mGluR4 were examined. (S)-4
      Carboxyphenylglycine (IC50 = 65 +/- 5 microM), (R,S)-alpha-methyl-4
      carboxyphenylglycine (IC50 = 155 +/- 38 microM) and (S)-3-carboxy-4
      hydroxyphenylglycine (IC50 = 290 +/- 47 microM) competitively antagonized
      glutamate-stimulated phosphoinositide hydrolysis in baby hamster kidney (BHK)
      cells stably expressing mGluR1 alpha. (S)-4-Carboxyphenylglycine and (R,S)-alpha
      methyl-4-carboxyphenylglycine competitively antagonized glutamate-induced
      inhibition of forskolin-stimulated cAMP-formation in BHK cells stably expressing
      mGluR2 with IC50 values of 577 +/- 74 microM and 340 +/- 59 microM, respectively.
      (R,S)-4-carboxy-3-hydroxyphenylglycine, (R)-3-hydroxyphenylglycine and (S)-3
      carboxy-4-hydroxyphenylglycine were agonists at mGluR2 with EC50 values of 48 +/-
      5 microM, 451 +/- 93 and 97 +/- 12 microM, respectively. In parallel experiments,
      no activities of these phenylglycine analogs at mGluR4 were observed. The present
      report demonstrates that phenylglycine analogs possess differential functional
      activities at subtypes of the mGluR family.

PMID- 7515824
TI  - Interferon-gamma modulates cAMP-induced mucin exocytosis without affecting mucin
      gene expression in a human colonic goblet cell line.
AB  - The regulation of intestinal mucin secretion by cytokines, soluble factors
      released by mucosal activated immune cells, is so far unknown. The aim of the
      present study was (1) to investigate the regulatory effects of interferon-gamma
      on baseline and stimulated mucin secretion elicited by an increase in
      intracellular cAMP, either a short-term increase (induced by vasoactive
      intestinal peptide or by forskolin) or a long-term increase (cholera toxin
      induced), and (2) to attempt to delineate the site of action of interferon-gamma.
      The in vitro model used was the human colonic goblet cell line Cl.16E, which has
      already been shown to respond to physiological secretagogues in terms of mucin
      secretion. We examined the effects of interferon-gamma 1) on mucin exocytosis,
      measured as release of [3H]glucosamine-labeled macromolecules trapped at the
      stacking/running gel interface of polyacrylamide gels, and 2) on mucin
      biosynthesis, examined at the RNA level using a cDNA probe directed to the MUC2
      mucin gene. We demonstrated that, while interferon-gamma did not alter baseline
      Cl.16E mucin secretion and MUC2 gene expression, it strongly inhibited the
      protein kinase A-dependent secretory response to VIP, forskolin, or cholera
      toxin. However, interferon-gamma had no effect on the protein kinase A-dependent
      MUC2 over-expression induced by cholera toxin. We thus concluded that the target
      for interferon-gamma inhibition of cAMP-stimulated Cl.16E mucin secretion is
      distal to protein kinase A and might be a component of the exocytotic machinery.
      Together, our results establish interferon-gamma as a pharmacologically powerful
      tool to specifically inhibit stimulated secretory processes without affecting
      baseline secretion.

PMID- 7515825
TI  - A nonhuman primate model for human cerebral malaria: rhesus monkeys
      experimentally infected with Plasmodium fragile.
AB  - We studied the brains of rhesus monkeys infected with the primate malaria
      parasite Plasmodium fragile. Electron microscopy showed that, in these animals,
      erythrocytes infected with P. fragile undergo sequestration and that parasitized
      red blood cells adhere to endothelial cells in the cerebral microvessels by means
      of knobs. Cerebral microvessels with sequestered parasitized red blood cells were
      shown by immunohistochemical analysis to possess the platelet glycoprotein CD36,
      thrombospondin, and intracellular adhesion molecule-1. The formation of rosettes
      also was observed in the cerebral microvessels. In a fashion similar to human
      cerebral malaria, P. fragile produced neurological symptoms in the animals. Thus,
      rhesus monkeys infected with P. fragile, like those monkeys infected with
      Plasmodium coatneyi, can be used as a primate model to study human cerebral
      malaria.

PMID- 7515826
TI  - Photochemical labeling of membrane-associated and channel-forming domains of
      proteins directed by energy transfer.
AB  - Singlet-singlet energy transfer reactions from excited tryptophan residues to
      photoactivatable probes possessing a suitable chromophore, generate reactive
      species in the vicinity of the protein, leading to its covalent labeling. This
      delayed labeling process can be used to map the membrane-surrounded regions of
      proteins with improved efficiency when it is applied with appropriate
      photoactivatable phospholipids. The same principle could also be applied to the
      labeling of channel-forming transmembrane domains of ion channels, provided that
      suitable photoactivatable permeant ions were available. Both applications will be
      discussed with regard to their potential and feasibility.

PMID- 7515827
TI  - Energy-coupled transport through the outer membrane of Escherichia coli small
      deletions in the gating loop convert the FhuA transport protein into a diffusion
      channel.
AB  - Active transport of Fe3+ as ferrichrome complex through the outer membrane of
      Escherichia coli is mediated by the FhuA outer membrane protein and the TonB-ExbB
      ExbD protein complex in the cytoplasmic membrane. The required energy is provided
      by the electrochemical potential of the cytoplasmic membrane which is assumed to
      induce a conformation of the TonB protein that causes a conformational change in
      FhuA so that bound ferrichrome is released into the periplasmic space located
      between the outer and the cytoplasmic membrane. Excision of segments as small as
      12 amino acids in the largest surface loop of FhuA converted FhuA into an open
      channel through which ferrichrome and antibiotics diffused independent of TonB
      ExbB-ExbD. It is proposed that FhuA forms a closed channel which is opened by
      movement of the gating loop through a kind of allosteric interaction with TonB.
      The gating loop is also involved in binding of all FhuA ligands which in addition
      to ferrichrome are the phages T1, T5, phi 80, colicin M and the antibiotic
      albomycin.

PMID- 7515828
TI  - Species variants of tachykinin receptor types.

PMID- 7515829
TI  - Protease activity and invasion of matrigel by the osteosarcoma-derived OSPR cell
      line.

PMID- 7515830
TI  - Nitric oxide toxicity in pancreatic islet cells: role of protein biosynthesis,
      calcium influx and arachidonic acid metabolism.

PMID- 7515831
TI  - Effects of cytokines and nitric oxide donors on insulin secretion, cyclic GMP and
      DNA damage: relation to nitric oxide production.

PMID- 7515833
TI  - The acute phase response.

PMID- 7515832
TI  - Ion channels and the molecular control of insulin secretion.

PMID- 7515835
TI  - Structural and molecular aspects of dioecy in Rumex acetosa.

PMID- 7515834
TI  - Neuropeptide Y-induced mast cell activation.

PMID- 7515836
TI  - Lipopolysaccharide binding protein: its role and therapeutical potential in
      inflammation and sepsis.

PMID- 7515837
TI  - The C-type carbohydrate recognition domain (CRD) superfamily.
AB  - The proteins of the CRD superfamily can be subdivided into six main groups, where
      members of a group have similar functions, molecular architecture and amino acid
      sequences. The determination of the tertiary structure of the CRD from MBP-A has
      defined the consensus structure for this module and can be considered a paradigm
      for the superfamily in general. The elegant work of Drickamer and colleagues has
      established the basic requirements for carbohydrate binding at both the tertiary
      and primary structure level, where the specificity of members of the CRD
      superfamily appears to correlate with specific sequence elements.

PMID- 7515838
TI  - Mannose binding protein.

PMID- 7515839
TI  - Immunolocalization and expression of insulin-like growth factor I (IGF-I) in the
      mammary gland during rat gestation and lactation.
AB  - We have studied the physiology and tissue expression of IGF-I and IGF-BP3 in
      pregnant and lactating rats. Specific assays (radioimmunoassays and a binding
      protein assay) were used to measure serum IGF-I, IGF-II, and IGF-BP levels. IGF-I
      and IGF-BP3 expression levels were determined in mammary gland and liver by slot
      blotting. A sensitive and IGF-I-specific ribonuclease (RNAse) protection assay
      was further used to detect RNAs transcribed from the IGF-I gene. In the first
      half of pregnancy, the maternal serum IGF-I concentration rises while the IGF-BP
      level decreases. This may modify IGF-I availability, thus promoting rapid tissue
      growth and differentiation. In the second half of pregnancy, the mean serum IGF-I
      concentration falls sharply from 1140 +/- 150 ng/ml at seven days of pregnancy to
      470 +/- 85 ng/ml at 20 days. Post-partum, serum IGF-I increases back to the level
      obtained in non-pregnant controls within 5 days. Serum levels of IGF-BP, during
      the same two periods, follow a similar pattern, decrease during pregnancy and
      increase after parturition. No IGF-II was detected at any time. From the onset of
      pregnancy to term, IGF-I gene expression in the mammary gland diminishes. In the
      liver, on the other hand, expression increases during very early pregnancy and
      diminishes thereafter, remaining below the level measured in non-pregnant animals
      from mid-pregnancy to term. The pattern of IGF-BP3 expression followed was
      similar in both organs, with a decrease during gestation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7515841
TI  - IGF-I stimulates granulosa cell-derived insulin-like growth factor binding
      protein-5: evidence for medication via type I IGF receptors.
AB  - Although the precise role of insulin-like growth factor binding proteins (IGFBPs)
      in ovarian physiology remains a matter of study, existing data suggest a possible
      antigonadotropic role in the context of follicular atresia. Given the above and
      the need for improved understanding of the regulation of ovarian IGFBPs, we have
      set out to explore the ability of IGF-I to modulate IGFBP levels in cultured rat
      granulosa cells. Specifically, granulosa cells (5 x 10(5) viable cells/dish) from
      immature (23-25 days old), estrogen-primed rats were cultured under serum-free
      conditions for 72 h in the absence or presence of IGF-I. At the conclusion of
      this incubation period, media samples were collected and subjected to Western
      ligand blotting. Treatment with IGF-I (100 ng/ml) resulted in a substantial (P <
      0.05) increase in the accumulation of IGFBP-5, the major 28-29 kDa IGFBP species.
      Subsequent studies revealed this effect of IGF-I to be both dose- and time
      dependent. A similar effect was noted for insulin at dose levels 1-10
      micrograms/ml at which cross-reaction with the type I IGF receptor (but not with
      IGFBPs) has been amply documented. Des (1-3) IGF-I, a type I receptor-selective
      ligand with markedly reduced avidity for IGFBPs, proved substantially more potent
      (as a promoter of IGFBP-5 accumulation) than its native counterpart. In contrast,
      treatment with IGF-II or [Leu27]IGF-II, type II IGF receptor-selective ligands,
      yielded a more limited effect on IGFBP-5 accumulation in keeping with an overall
      rank order of potency of des (1-3) IGF-I > IGF-I > IGF-II > or = [Leu27]IGF
      II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515840
TI  - Effect of transforming growth factor-beta 1 on the insulin-like growth factor
      system in cultured porcine Leydig cells.
AB  - Using as a model system, primary cultures of porcine Leydig cells, we have shown
      that transforming growth factor-beta 1 (TGF-beta 1) (2 ng/ml, 72 h) antagonizes
      the stimulatory action of insulin-like growth factor-I (IGF-I) on luteinizing
      hormone (LH/hCG) receptors. We therefore investigated the action of TGF-beta 1 on
      the different components of the IGF system, namely, IGF-I, II, IGF binding
      proteins (IGFBPs) and IGF-I receptor present in testicular Leydig cells. TGF-beta
      1 was shown to decrease in a dose and time dependent manner the binding of 125I
      IGF-I to Leydig cells. The maximal (40% decrease) effect was obtained with 1.3
      ng/ml (0.05 nM) after 72 h of treatment. Such a decrease in IGF-I binding by TGF
      beta 1 treatment was shown to be related to the number of receptor but not to
      their affinity. Affinity labeling of these receptors by covalently binding them
      to 125I-IGF-I with disuccinimidyl suberate and subsequent electrophoretic
      analysis of the labeled complex revealed that the inhibitory action of TGF-beta 1
      (2 ng/ml, 72 h) occurs at the level of a 135 kDa protein which represents the
      classical form of the binding subunit of the IGF-I receptor. Moreover, our study
      indicates that TGF-beta 1 was unable to affect the other components of the IGF
      system in cultured porcine Leydig cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515843
TI  - Bleomycin, cisplatinum and ifosfamide infusion chemotherapy in advanced/recurrent
      cancer of cervix.
AB  - Twenty one patients age ranging from 26-70 years, with biopsy proven
      recurrent/advanced carcinoma of the cervix were treated with bleomycin,
      cisplatinum and ifosfamide infusion therapy. 88% patients reported subjective
      improvement. The objective response rate was 66.6% (Complete 38% and partial
      28.5%). Side effects were mainly nausea, vomiting, and alopecia. Treatment
      related fever was common. Hematuria and reversible encephalopathy with ifosfamide
      were seen in three and two patients respectively. These results indicate that BIP
      infusion chemotherapy is an active and safe combination for treatment of
      advanced/recurrent cervical cancer.

PMID- 7515842
TI  - Treatment of early stage prostate cancer: radiotherapy.
AB  - PATIENTS with T1/T2 prostate cancer are well served by external beam radiation.
      1. T1/T2, N0, M0 PATIENTS: The 10-year outcome of N0 patients is equal to that
      obtained by radical prostatectomy in similar patients without the operative
      mortality or incontinence that accompanies the latter procedure. Ten-year cure
      has been confirmed by PSA studies in irradiated patients, while this has not yet
      been demonstrated in surgical patients. 2. T1, NX, M0 PATIENTS: After radiation
      therapy these patients show no excess mortality as long as 15 years after
      treatment, an outcome confirming a strict criteria of cure. 3. T2, NX PATIENTS:
      After radiation therapy, these patients show continuing excess mortality to 15
      years, but most 15-year survivors are NED, again supporting the concept of long
      term cure. 4. T1/T2 N+, M0 PATIENTS: We must have clinical trials in these
      patients that study the roles of radiation, androgen deprivation, and surgery. 5.
      Conformal treatment technology is improving the technical delivery and dose
      administered by radiation therapy and decreasing both the acute and late side
      effects of treatment. It remains to be proved whether the increased dose and
      accuracy will improve local control and cure as hoped.

PMID- 7515844
TI  - Intraluminal brachytherapy in carcinoma of the oesophagus: comparison of
      afterloading techniques.
AB  - For improved local control or palliation of oesophageal cancers, Intra-luminal
      brachytherapy (ILB) has emerged as an increasingly popular treatment modality of
      therapy in recent years. In combination with external radiotherapy, afterloaded
      ILB can increase local control rates and may prolong survival of these patients.
      In this paper two techniques of ILB viz., manual and low dose-rate remote after
      loading methods, using Caesium-137 tubes and pellets respectively, are described
      in detail. On comparison of these two techniques it was found that both of them
      were similar with respect to their physical characteristics (dose rate, dose fall
      off, maximum spinal cord dose, total reference air kerma, etc.). Clinically, the
      manual afterloaded ILB technique was found to be easier to use when compared with
      the low-dose rate remote afterloader. In addition, the number of patients with
      uterine cancers being high in a developing country, it was found that it was
      inappropriate to use the low dose remote afterloaders, designed for use in
      gynaecological cancers, for ILB of oesophageal cancers. Therefore, in the absence
      of high dose rate afterloaders, which can be utilized for intracavitary
      treatments of both uterine and oesophageal malignancies effectively, the manual
      after-loading ILB system as described in this paper could be a practical
      alternative. Cancer Oesophagus, Intraluminal radiotherapy technique.

PMID- 7515845
TI  - Maxillary extragonadal germ cell tumor: a case report.
AB  - A single case report of a patient with primary extragonadal endodermal sinus
      tumor affecting the maxillary region is reported here. The patient was treated
      with combination chemotherapy consisting of bleomycin, cisplatin and etoposide.
      The child achieved complete remission and is now disease free for three years.

PMID- 7515846
TI  - IFN-gamma abrogates IL-7-dependent proliferation in pre-B cells, coinciding with
      onset of apoptosis.
AB  - These studies investigated the mechanism by which interferon-gamma (IFN-gamma)
      inhibits the interleukin-7 (IL-7)-dependent proliferation of BALB/c bone marrow B
      cell precursors in vitro. Low concentrations (1 U/ml) of recombinant murine IFN
      gamma (rmIFN-gamma) caused a approximately 80% suppression of IL-7 colony-forming
      units (CFU) formation in semi-solid media, in part through a direct affect on
      isolated B220+ pre-B cells. IFN-gamma did not induce apoptosis in small resting
      pre-B cells in BALB/c bone marrow. There was no difference in the proportion of
      apoptotic B220+ pre-B cells in IFN-gamma-treated cultures compared to cultures
      treated with IL-7 alone. However, IL-7-responsive pre-B cells generated from bone
      marrow had a 30-50% loss in cells in S+G2/M phases of the cell cycle and an
      increase of up to twice as many in apoptotic cells within 48 hr of exposure to
      IFN-gamma. Notably, expression of the tyrosine phosphatase B220 was increased in
      the IFN-gamma-treated pre-B cells. Interestingly, although there was no
      substantial change in IL-7 receptor mRNA expression upon IFN-gamma treatment, a
      small decrease in binding of biotinylated IL-7 to IFN-gamma-treated pre-B cells
      was observed. These results suggest that IFN-gamma inhibits IL-7 responsiveness
      in pre-B cells, resulting in a subtle down-regulation of IL-7 binding, inhibition
      of proliferation and, ultimately, apoptosis.

PMID- 7515847
TI  - Site-directed primary in vitro immunization: production of HIV-1 neutralizing
      human monoclonal antibodies from lymphocytes obtained from seronegative donors.
AB  - The design of an in vitro immunization system based on a synthetic heterotope
      immunogen, which was a peptide containing both T- and B-cell epitopes, that
      elicited a neutralizing, primary human humoral immune response against the human
      immunodeficiency virus (HIV-1) is reported here. This heterotope construct
      contained the major neutralizing B-cell epitope, within the V3 region of
      glycoprotein 120 (gp120), linked to a promiscuous helper T-cell epitope of
      tetanus toxin. The peptide was used to induce a human humoral in vitro immune
      response against the V3 region, using lymphocytes obtained from healthy, sero
      negative blood donors. The in vitro immunized peripheral blood lymphocytes were
      Epstein-Barr virus infected and the antibody response to the synthetic peptide
      was evaluated using a solid-phase ELISA with the recombinant C-terminal fragment
      of gp120 (pB1, amino acid residues 287-467, derived from the HIV-1 LAI isolate).
      The heterotope construct yielded a significantly frequency of specifically
      immunized B cells, in contrast to the control immunizations with individual T and
      B epitopes, mixtures of these epitopes or no immunogen at all. This approach
      allowed us to generate human monoclonal antibodies, using lymphocytes derived
      from sero-negative donors, that cross-neutralized several HIV-1 strains,
      inhibited syncytia formation as well as prevented spreading of the viral
      infection from cell to cell. Thus, site-directed in vitro immunization using
      synthetic heterotopes might prove valuable in the dissection and induction of a
      protective humoral immune response.

PMID- 7515848
TI  - A murine cytomegalovirus-neutralizing monoclonal antibody exhibits autoreactivity
      and induces tissue damage in vivo.
AB  - The autoreactivity of murine cytomegalovirus (MCMV)-neutralizing monoclonal
      antibody (mAb) AC1 was examined in vitro and in vivo. Both mAb AC1 and a human
      antiserum reactive with U1-small nuclear ribonucleoprotein (U1-snRNP) stained
      uninfected mouse embryo fibroblasts (MEF) in a speckled nuclear pattern and
      reacted with 70,000 molecular weight (MW) MEF nuclear antigens by immunoblotting,
      suggesting that mAb AC1 cross-reacted with the 70,000 MW component of U1-snRNP.
      However, only mAb AC1 cross-reacted with an additional epithelial cytoplasmic
      autoantigen present in cultured HEp2 cells. On tissue sections from uninfected
      mice, mAb AC1 predominantly reacted with a component of central and peripheral
      nervous systems, although cross-reactivity with the stratum spinosum of the skin
      and the outer sheath of hair follicles was also observed. Immunoblotting revealed
      that mAb AC1 reacted with phosphorylated epitopes present on a 98,000 MW MCMV
      structural protein and the 200,000 MW mouse neurofilament protein (NFP).
      Treatment of uninfected mice with mAb AC1 resulted in a severe interstitial
      pneumonia with greatly thickened and congested alveolar septa. Severe oedema of
      the hypodermis and a mild mesangial proliferative glomerulonephritis were also
      observed. These results demonstrate that a mAb reacting with a MCMV structural
      phosphoprotein which can protect mice against the dissemination of MCMV, can also
      promote the development of autoimmune disease. Therefore, the production of such
      cross-reactive antibodies may be an important mechanism in the development of
      autoimmunity following viral infection.

PMID- 7515851
TI  - Two distinct interleukin-1 beta genes in the pig genome.

PMID- 7515850
TI  - Differential expression of complement regulatory proteins decay-accelerating
      factor (CD55), membrane cofactor protein (CD46) and CD59 during human
      spermatogenesis.
AB  - We have examined the distribution of the complement (C) regulatory proteins CD59,
      membrane cofactor protein (MCP) and decay-accelerating factor (DAF) on mature
      sperm and compared expression of these proteins in parallel both during
      spermatogenesis and in the prostate. Enhanced immunoperoxidase staining and
      radioimmunoassay confirmed that C regulators are differentially expressed on
      sperm; CD59 was strongly expressed on the surface of acrosome intact sperm while
      MCP and DAF appear to be located primarily on the inner acrosomal membrane. While
      the MW of CD59 on sperm is typical of other systems, we confirm that in addition
      to a novel 40,000-46,000 MW MCP protein, sperm also express a novel 55,000 MW DAF
      product. Examination of normal testis by immunostaining revealed that although C
      regulators are differentially expressed within the germinal epithelium, all three
      proteins were present on the acrosomal region of condensing spermatids. We show
      that novel, low MW forms of MCP and DAF are expressed in normal testis membranes
      but are absent from testis membranes obtained from patients undergoing gender
      reassignment surgery in whom the germinal epithelium is diminished. Novel MW C3
      convertase regulators are therefore associated with differentiating germinal
      epithelium. Typical CD59 components were also present on normal testis membranes
      confirming that CD59 is acquired during spermatogenesis. We demonstrate that the
      prostatic epithelium, in addition to MCP, expresses CD59 but not DAF. By
      comparison with CD59, therefore, our studies suggest that DAF may be acquired
      only in the testis. Overall, our data suggest that, on leaving the testis, sperm
      express the repertoire of C regulators required for protection from C during
      their transit through the male and female reproductive tracts.

PMID- 7515849
TI  - Tissue distribution of complement regulatory membrane proteins in rats.
AB  - Complement regulatory membrane proteins act either on C3/C5 convertase enzymes of
      the classical and alternative pathways or prevent the formation of membrane
      attack complexes (MAC). 5I2 is a monoclonal antibody (mAb) directed against a rat
      erythrocyte membrane inhibitor of the C3 convertase step which seems to be the
      rat counterpart of mouse Crry/p65. 6D1 is a mAb against rat CD59 which inhibits
      formation of MAC. Tissue distribution of these membrane inhibitors was visualized
      by immunohistochemical staining with the appropriate mAb. Rat CD59 (6D1 antigen)
      and 5I2 antigen were both widely distributed, being predominantly expressed on
      endothelial cells of the arteries, veins and capillaries as well as on all
      circulating cells. 6D1 antigen and 5I2 antigen were also detected on immature
      hepatocytes, systemic endothelial cells, skin fibroblasts, bronchial epithelial
      cells and bile canaliculi. Both were also expressed in the Schwann sheath of
      peripheral nerve fibres and ependymal cells. However, glial cells and myelin
      sheath in the central nervous system were not stained. Anti-CD59 (6D1) staining
      of epithelial and endothelial cells was observed in the cornea, while 5I2 stained
      only the epithelial cell layer.

PMID- 7515853
TI  - Nitric oxide synthase isozymes. Characterization, purification, molecular
      cloning, and functions.
AB  - Three isozymes of nitric oxide (NO) synthase (EC 1.14.13.39) have been identified
      and the cDNAs for these enzymes isolated. In humans, isozymes I (in neuronal and
      epithelial cells), II (in cytokine-induced cells), and III (in endothelial cells)
      are encoded for by three different genes located on chromosomes 12, 17, and 7,
      respectively. The deduced amino acid sequences of the human isozymes show less
      than 59% identity. Across species, amino acid sequences for each isoform are well
      conserved (> 90% for isoforms I and III, > 80% for isoform II). All isoforms use
      L-arginine and molecular oxygen as substrates and require the cofactors NADPH,
      6(R)-5,6,7,8-tetrahydrobiopterin, flavin adenine dinucleotide, and flavin
      mononucleotide. They all bind calmodulin and contain heme. Isoform I is
      constitutively present in central and peripheral neuronal cells and certain
      epithelial cells. Its activity is regulated by Ca2+ and calmodulin. Its functions
      include long-term regulation of synaptic transmission in the central nervous
      system, central regulation of blood pressure, smooth muscle relaxation, and
      vasodilation via peripheral nitrergic nerves. It has also been implicated in
      neuronal death in cerebrovascular stroke. Expression of isoform II of NO synthase
      can be induced with lipopolysaccharide and cytokines in a multitude of different
      cells. Based on sequencing data there is no evidence for more than one inducible
      isozyme at this time. NO synthase II is not regulated by Ca2+; it produces large
      amounts of NO that has cytostatic effects on parasitic target cells by inhibiting
      iron-containing enzymes and causing DNA fragmentation. Induced NO synthase II is
      involved in the pathophysiology of autoimmune diseases and septic shock. Isoform
      III of NO synthase has been found mostly in endothelial cells. It is
      constitutively expressed, but expression can be enhanced, eg, by shear stress.
      Its activity is regulated by Ca2+ and calmodulin. NO from endothelial cells keeps
      blood vessels dilated, prevents the adhesion of platelets and white cells, and
      probably inhibits vascular smooth muscle proliferation.

PMID- 7515852
TI  - Endothelin mobilizes calcium and enhances glucose uptake in cultured human
      skeletal myoblasts and L6 myotubes.
AB  - In this study we used endothelin as a paradigm to explore the concept that some
      vasoactive agents, acting through mobilization of Ca2+ and stimulation of protein
      kinase C, can interact with human skeletal muscle and modify its glucose
      transport. Cultured human skeletal myoblasts from the vastus lateralis
      demonstrated two subclasses of high-affinity endothelin receptors and a robust
      increase in cytosolic free Ca2+ upon exposure to endothelin. The endothelin
      evoked rise in cytosolic free Ca2+ primarily resulted from Ca2+ mobilization from
      intracellular organelles. Both endothelin and insulin enhanced [3H]deoxy-D
      glucose uptake in human myoblasts, but their effects were not additive. These
      findings also were observed in differentiated myotubes of L6 skeletal muscle
      cells. Moreover, [3H]deoxy-D-glucose uptake in human myoblasts was enhanced by
      treatment with phorbol 12-myristate 13-acetate. The endothelin- and insulin
      mediated increases in [3H]deoxy-D-glucose were totally ablated by treatment with
      calphostin C. Such observations suggest that endothelin can enhance glucose
      uptake in human skeletal muscle. This is mediated through mechanisms that are at
      least partially protein kinase C dependent. Thus, increased levels of endothelin
      in vascular beds may contribute to altered glucose metabolism in essential
      hypertension.

PMID- 7515855
TI  - Long-term nitric oxide synthase inhibition and distensibility of carotid artery
      in intact rats.
AB  - The goal of the present study was to evaluate the effect of long-term nitric
      oxide synthase inhibition by NG-nitro-L-arginine-methyl ester (L-NAME) on the
      morphology and viscoelastic properties of the carotid arteries in rats. Twelve
      week-old Wistar-Kyoto rats were treated for 6 weeks with either the nitric oxide
      synthase inhibitor L-NAME (0.4 g/L in drinking water; L-NAME rats, n = 13) or tap
      water (control rats, n = 13). Age-matched spontaneously hypertensive rats (SHR, n
      = 14) received tap water for the same period. The internal diameter of the common
      carotid artery was measured continuously with an echo-tracking device with the
      rats under anesthesia with halothane. Intra-arterial pressure was monitored on
      the contralateral side. L-NAME rats exhibited arterial pressures similar to those
      of SHR. The distensibility pressure-curve determined in L-NAME rats was a direct
      continuation of that obtained in control rats. In contrast the distensibility in
      SHR was increased (P < .01, SHR versus L-NAME rats). Carotid artery cross
      sectional area and left ventricular weight index were increased similarly in SHR
      and L-NAME rats compared with control rats. Thus the hypertension caused by long
      term nitric oxide synthesis inhibition was not associated with the increased
      arterial distensibility observed in SHR despite similar blood pressure
      elevations, similar arterial hypertrophy, and consequently similar wall stress.
      This suggests a role for nitric oxide in regulating the mechanical behavior of
      arteries exposed to high blood pressure.

PMID- 7515854
TI  - Role of kinins and nitric oxide in the antihypertrophic effect of ramipril.
AB  - We examined the effect of non-antihypertensive doses of the angiotensin
      converting enzyme inhibitor ramipril, kinins, and/or nitric oxide on left
      ventricular hypertrophy in rats with aortic coarctation. We investigated the
      effect of either HOE 140, a specific B2 receptor antagonist, or NG-nitro-L
      arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the
      antihypertrophic effect of ramipril at non-antihypertensive doses (10
      micrograms/kg per day) failed to alter left ventricular hypertrophy
      significantly, although a small decrease was obtained. Given at a dose of 1 mg/kg
      per day for 6 weeks, ramipril prevented increased blood pressure and left
      ventricular hypertrophy after aortic coarctation. Neither of these effects was
      blocked by simultaneous administration of HOE 140 (500 micrograms/kg per day). In
      rats with aortic coarctation treated with L-NAME, blood pressure increased
      further but left ventricular weight did not. Ramipril (1 mg/kg per day)
      significantly reduced left ventricular hypertrophy, although blood pressure was
      still higher than in rats given water alone. The slope of the correlation between
      left ventricular weight and blood pressure in rats that received L-NAME was
      significantly lower than in rats that did not (0.52 versus 1.29; P = .008). This
      suggests that for each 1 mm Hg that the blood pressure increased, the increase in
      left ventricular weight was less in the L-NAME groups. Thus, only
      antihypertensive doses of ramipril possessed antihypertrophic activity. Kinins
      did not participate in the chronic antihypertensive and antihypertrophic effects
      of ramipril. In hypertension induced or aggravated by chronic nitric oxide
      synthase, L-NAME partially impaired development of left ventricular hypertrophy
      for reasons that are unclear.

PMID- 7515856
TI  - Inhibition of angiogenesis in rats by IL-1 receptor antagonist and selected
      cytokine antibodies.
AB  - Daily administration of 50 ng recombinant human interleukin 1-alpha (IL-1 alpha),
      25 ng IL-8, 50 ng tumor necrosis factor-alpha (TNF-alpha), or 100 ng basic
      fibroblast growth factor (bFGF) caused intense neovascularization in a rat sponge
      model. These cytokine-induced neovascular responses were inhibited by
      coadministration of IL-1 receptor antagonist (IL-1ra; 50 micrograms), IL-8
      antiserum (IL-8-AS; 1: 1000), TNF-alpha antibody (TNF-AB; 500 ng), or a
      monoclonal antibody to bFGF (DG2; 1000 ng), respectively. These data suggest that
      it is possible to manipulate the angiogenic response elicited by a defined
      cytokine by its receptor antagonist or neutralizing antibody. In the absence of
      exogenous cytokines, the sponge-induced angiogenesis was profoundly suppressed by
      dexamethasone (5 micrograms/day), but not modified by IL-1ra, IL-8-AS, TNF-AB,
      and DG2 alone. However, the combination of these four reagents was able to
      inhibit the sponge-induced neovascular response almost completely. These findings
      provide direct evidence that IL-1 alpha, IL-8, TNF-alpha and/or bFGF have an
      intrinsic role in angiogenesis. Further work is necessary to characterize the
      profile of these cytokines during angiogenesis and to elucidate the nature of
      their interactions.

PMID- 7515857
TI  - Differences in altered expression of L-selectin and Mac-1 in monocytes and
      neutrophils.
AB  - We have measured the altered expression of the adhesion-promoting glucoproteins L
      selectin and Mac-1 on monocytes and neutrophils after incubation with different
      concentrations of the chemotactic factor FMLP. We found a time- and dose-related
      down-regulation of L-selectin on both monocytes and neutrophils, which was more
      pronounced on neutrophils as compared to monocytes at both low (10(-12) M) and
      high (10(-7) M) concentrations of the chemotactic factor FMLP. Presence of human
      albumin reduced the down-regulation of L-selectin on both monocytes and
      neutrophils but to a greater extent on monocytes. Mac-1 expression increased in a
      time and dose-dependent manner on both monocytes and neutrophils when they were
      incubated with both low (10(-12) M) and high (10(-7) M) concentrations of FMLP,
      but the expression was more pronounced on neutrophils. The up-regulation of Mac-1
      was equally reduced by albumin on monocytes and neutrophils. Presence of EDTA in
      RPMI medium reduced the FMLP-induced down-regulation of L-selectin on both
      monocytes and neutrophils, indicating that the down-regulation of L-selectin is
      partly divalent cation dependent. Differences in the altered expression of L
      selectin and Mac-1 in monocytes and neutrophils with sustained expression of L
      selectin on monocytes can contribute to the sequential recruitment of these cells
      into an inflammatory site.

PMID- 7515858
TI  - Peptidoleukotriene (pLT) release from guinea pig lung mast cells.
AB  - Guinea pig lung mast cells can be isolated and purified to high purity. This has
      given us the opportunity to study in greater detail mediator release from these
      cells. Both immunologic (ovalbumin sensitized) and nonimmunologic (calcium
      ionophore, CaI) stimuli caused a dose-dependent release of histamine and pLT from
      monodispersed lung cells and highly purified lung mast cells. Examination of the
      time release curve for pLT revealed a 5-min lag in the release of this mediator
      and a peak release at 60 min after challenge with antigen. Verification of pLT
      release was obtained by use of the 5-lipoxygenase inhibitor A64077 (Zileuton).
      Pretreatment of lung mast cells with the 5-lipoxygenase inhibitor prevented
      release of pLT by either antigen or CaI but had no appreciable effect on
      histamine release (HR). The pulmonary mast cell appears to be an important
      contributor to pLT release in the guinea pig lung.

PMID- 7515859
TI  - Phorbol ester induced rapid attachment and spreading of melanoma cells and the
      role of extracellular matrix proteins.
AB  - Phorbol 12-myristate 13-acetate (PMA) is a tumour promotor that acts as a potent
      protein kinase C (PKC) activator that has significant effects on tumour cell
      attachment and spreading. We tested whether these effects of PMA may be observed
      in human melanoma cells, and whether a specific response to extracellular matrix
      proteins may be mediated by shifts in the expression of beta 1 integrins. We used
      cell attachment assays, video time lapse cell spreading assays, flow cytometry,
      function blocking monoclonal antibodies (MAbs) and PKC inhibitor Calphostin C to
      address these questions. We established that PMA induces a rapid and temporary
      enhancement of cell attachment and spreading which was not accompanied by a
      significant change in the expression of beta 1 integrins. Spreading of melanoma
      cells that were not stimulated with PMA could be significantly blocked with a
      function blocking MAb (clone P4C10) against the common beta 1 integrin subunit.
      The spreading and attachment of the PMA treated cells was also significantly
      reduced, but less so, after MAb treatment. The PMA enhanced cell attachment and
      spreading could be effectively blocked by RGD sequences and PKC inhibitor. Taken
      together, our data indicate that PMA induces a rapid and temporary ECM-dependent
      enhancement of melanoma cell attachment and spreading, and that the response to
      ECM components appears not to be due to significant shifts in beta 1 integrin
      expression, but rather to activation of beta 1 integrins.

PMID- 7515860
TI  - E-selectin binding by pancreatic tumor cells is inhibited by cancer sera.
AB  - Tumor cells interact with endothelial cells during both intra- and extravasation.
      Understanding how these interactions are modulated could lead to the development
      of ways to alter the metastatic potential of tumor cells. Three pancreatic cancer
      cell lines, SW1990, CAPAN-2 and PANC-I, were examined for their ability to bind
      to the endothelial cell adhesion molecule E-selectin (ELAM-1). SW1990 cells
      exhibited highest binding, highest surface expression of the carbohydrate
      antigens sialylated Lewis(a) (sLe(a)) and sialylated Lewis(x) (sLe(x)) and
      released the most high m.w. sLe(a) and sLe(x) antigens. Expression of sLe(a) and
      sLe(x) antigens and binding to E-selectin were reduced by pre-treatment of SW1990
      cells with the O-linked glycosylation inhibitor benzyl-alpha-GalNAc but not with
      the N-linked glycosylation inhibitor tunicamycin. Expression of peptide epitopes
      associated with MUC1 apomucins was increased by benzyl-alpha-GalNAc. Cell binding
      was greatly reduced by mucins purified from SW1990 xenografts and by an antibody
      against sLe(a). An antibody against sLe(x) had a much less marked effect. Sera
      from pancreatic cancer patients reduced SW1990 cell binding to E-selectin but
      sera from normals did not. The degree of inhibition was related to the sLe(x)
      level in the sample. When cancer serum was separated by column chromatography on
      Sephacryl S-400, the void volume fractions contained most of the sLe(a) and
      sLe(x) antigens and most of the inhibitory activity to E-selectin binding.
      Differences in the relative availability of sLe(a) and sLe(x) ligands on serum
      molecules and on the SW1990 cell surface may account for the differences between
      antibody and serum inhibition results. Thus SW1990 cell adhesion to E-selectin is
      mediated by ligands on mucinous glycoproteins, and adhesion can be inhibited by
      mucins, high blood levels of sLe(x) and reduction of cellular O-linked
      glycosylation.

PMID- 7515861
TI  - Potentiation of cytotoxic cancer therapies by TNP-470 alone and with other anti
      angiogenic agents.
AB  - The ability of TNP-470, a synthetic analog of fumagillin which has been described
      as an anti-angiogenic agent, to potentiate cytotoxic cancer therapies was
      investigated in vivo in the murine FSaIIC fibrosarcoma and the Lewis lung
      carcinoma. TNP-470 was more toxic toward FSaIIC tumor cells from tumors treated
      in vivo than toward bone-marrow CFU-GM from the same animals. TNP-470 had a dose
      modifying effect on the toxicity of cyclophosphamide toward FSaIIC tumor cells
      which amounted to an 8-fold increase in tumor-cell killing at a cyclophosphamide
      dose of 500 mg/kg. Treatment with TNP-470 and minocycline increased the
      permeability of the FSaII fibrosarcoma in vivo to the fluorescent dye Hoechst
      33342 and increased the killing of both the bright and the dim tumor cells by
      cyclophosphamide. TNP-470, especially in combination with minocycline, formed a
      highly effective modulator combination for treatment of the Lewis lung carcinoma
      with cytotoxic cancer therapies against primary and metastatic disease. The
      combination of TNP-470/minocycline and cyclophosphamide led to 40 to 50% long
      term survivors in Lewis-lung-carcinoma-bearing animals. Our results indicate that
      the use of anti-angiogenic modulators in cancer therapy is a very promising area
      for further study.

PMID- 7515862
TI  - Teaching of patients undergoing total hip replacement surgery.
AB  - We studied the effect of patient teaching in 60 patients who underwent primary
      total hip replacement surgery. All the patients received an illustrated patient
      guide. In addition to the general patient teaching given by doctors, nurses and
      physiotherapists, a randomly chosen group of 27 patients received a session of
      intensified patient teaching. At the follow-up, 2-3 months postoperatively, 61%
      of patients thought that they had received the main part of their information
      from the physiotherapists, 9% from their doctors and 4% from the nursing staff.
      The importance of a well-illustrated guide was pointed out. The knowledge of
      potential complications, such as infection, remained poor; 37% could not name one
      single relevant complication. At the follow-up, the younger or better educated
      patients did not score any better. The experimental group who had received
      intensified teaching differed only slightly from the controls, but they knew
      significantly better when to inform their doctor of potential complications.
      Also, the experimental group showed greater interest in obtaining more
      information about their replaced hip. Patients in the experimental group showed
      significantly better adherence to the instructions for the postoperative
      rehabilitation programme.

PMID- 7515863
TI  - Peptidergic pathway in human skin and rat peritoneal mast cell activation.
AB  - The common pathway of heterogenous mast cell activation as mediated by antigens
      is through the cross-linking of IgE bound to Fc epsilon RI receptors. The
      peptidergic pathway of mast cell activation, achieved by cationic secretagogues,
      is restricted to "serosal" mast cells, the experimental models being rat
      peritoneal and human skin mast cells. Cationic secretagogues include positively
      charged peptides but also various amines such as compound 48/80 and natural
      polyamines. An early intracellular event of this pathway is the activation of
      pertussis toxin-sensitive G proteins. The correlation observed between the
      ability of basic compounds to trigger mast cell exocytosis and their potency to
      activate purified G proteins strongly suggests that cationic compounds activate
      mast cell G proteins via a receptor-independent but membrane-assisted process. In
      this paper, alternative mechanisms are discussed. The consequence of G protein
      stimulation is the activation of phospholipase C with an increase in inositol
      triphosphates. Natural polyamines are relatively poor triggers of mast cells (10(
      4) to 10(-2) M). Neuropeptides such as substance P, neuropeptide Y or vasoactive
      intestinal peptide, peptidic hormones such as kinins, and venoms such as
      mastoparan and mast cell degranulating peptide, are all active in a concentration
      range from 10(-7) to 10(-4) M. The cationic anaphylatoxin C3a also stimulates
      mast cells at concentrations below precursor complement C3 blood levels. The
      component C3 of the complement system is one of only a few plasma proteins having
      activation fragments (i.e. C3a) that can be generated at micromolar levels. The
      effects of basic secretagogues defines a peptidergic pathway of mast cell
      activation, which represents a potentially toxic process considering the tissue
      effects caused by exogenous basic compounds such as venom peptides and certain
      amine containing drugs. Peptidergic activation of mast cells may also be a
      pathophysiological process having an important role in neurogenic inflammation
      and in diseases involving extensive activation of the blood complement cascade.

PMID- 7515864
TI  - Interferon-gamma-activated macrophages enhance angiogenesis from endothelial
      cells of rat aorta.
AB  - The influence of interferon-gamma (IFN-gamma), an activator of macrophages, was
      investigated on angiogenesis in vitro from rat aortic endothelial cells (EC).
      Subcultured EC were cultured in 0.15% type I collagen gel with 2% fetal bovine
      serum (FBS)-Dulbecco's modified Eagle's medium. Tube formation by EC began on the
      first day of culture and reached a plateau that lasted from the second to the
      eighth day. A peritoneal macrophage preparation was co-cultured on overlaying
      collagen gel containing EC. The macrophage preparation increased tube length from
      the second to the fourth day in a time-dependent manner. IFN-gamma (2.2 and 6.5
      ng/ml) enhanced the effect of co-cultured macrophages from the fourth to the
      eighth day. The conditioned media derived from macrophages after 4 and 6 days of
      exposure to IFN-gamma (6.5 ng/ml) also showed significantly enhanced tube
      formation induced by macrophage-conditioned medium. However, IFN-gamma (6.5
      ng/ml) did not influence the activity of the macrophage-conditioned medium. These
      results suggest that IFN-gamma enhances angiogenesis from EC of rat aorta by
      releasing an angiogenic factor from macrophages.

PMID- 7515866
TI  - Polysaccharide distribution in the cellular junctions of immature fibre cells of
      flax seedlings.
AB  - The characteristic features of the pectins present in the walls of immature fibre
      cells of the hypocotyl of flax seedlings have been studied by a combination of
      three subtractive methods (treatment with boiling water, calcium chelator, and
      free endopolygalacturonase), three staining reactions (periodic acid
      thiocarbohydrazide-silver, Ruthenium Red, and ferric hydroxylamine) and labelling
      with an endopolygalacturonase-gold probe. The primary wall and the periphery of
      the tricellular junctions were shown to contain pectic molecules made of blocks
      either with free acidic functions or methyl-esterified, these molecules being
      removed from the wall by splitting alpha (1-4) linkages. On the contrary, the
      pectic molecules in the core of the tricellular junctions were mainly with free
      acidic groups, but with an appreciable acetylesterification of their hydroxyl
      groups; and they were linked with one another chiefly by calcium bonds. This
      unexpected constitution of the core of the tricellular junctions may be
      considered to be an early marker of the cells destined to give rise to the fibre
      bundles of the mature plant.

PMID- 7515867
TI  - Histochemical and ultrastructural studies of mast cells in the intestinal mucosa
      and skin of the opossum Didelphis albiventris.
AB  - The mast cells located in the intestinal mucosa of a non-eutherian mammal were
      studied in comparison with those in the skin of the ear. In the intestinal
      mucosa, the mast cells exhibited a more variable shape, larger cytoplasmic
      granules and greater sensitivity to fixatives regarding their staining towards
      Toluidine Blue. Ultrastructurally, these granules were more heterogeneous but
      lacked the crystalline content found in granules of skin mast cells; lipid body
      like organelles were found only in the mucosa-located mast cells.
      Histochemically, they differed from skin mast cells by the absence of periodic
      acid-Schiff (PAS)-positive granules. Unlike the mucosal mast cells of the rat,
      they fluoresced brilliant yellow after berberine treatment, which is evidence of
      the presence of heparin.

PMID- 7515868
TI  - Light microscopical detection of inter-alpha-trypsin inhibitor and its different
      mRNAs in cultured hepatoma Hep G2 cells using immunocytochemical and in situ
      hybridization techniques.
AB  - The Hep G2 hepatoma cell line synthesizes the inter-alpha-trypsin inhibitor
      (ITI). This protease inhibitor and the other proteins of this family include four
      polypeptides chains: three heavy chains (HC1, HC2, HC3) and one light chain
      (bikunin). In the present study, we have demonstrated by immunofluorescence that
      ITI is detected mainly in perinuclear cytoplasmic zones comparable to those of
      albumin or alpha-1-antitrypsin. The presence of the mRNAs of the four polypeptide
      chains in all Hep G2 cells of a non-synchronized culture have been demonstrated
      by in situ hybridization. An evaluation of the transcription of the four ITI
      genes through an analysis of markings brings to the fore a clearly much higher
      rate of mRNAs from the light chain than from the heavy chains. The mRNAs
      corresponding to the HC2 chains are more heavily represented than are those
      corresponding to the HC1 and HC3 chains. In Hep G2 cells in culture, a
      quantification of mRNAs based on the in situ hybridization technique shows that
      their relative quantities, in decreasing order, are those of L, HC2, HC3 and HC1.

PMID- 7515865
TI  - Cuprolinic blue visualization of cytosolic and membrane-associated
      glycosaminoglycans in the rat junctional epithelium and gingival epithelia.
AB  - The gingiva of rat molars was studied at the light microscope level using
      glutaraldehyde as fixative, Cuprolinic Blue for visualizing polyanionic
      glycosaminoglycans and the autometallographic technique for enhancing the copper
      signal of the cationic dye. The polyanions were located inside the epithelial
      cells in the junctional epithelium, whereas a network located along either the
      plasma membrane or the intercellular spaces, or both, of the gingival oral
      epithelium and sulcular oral epithelium was evident with autometallography. In
      these cases, positive staining was limited to the basal and spinous layers, the
      granular and keratinized layers being unstained. With the transmission electron
      microscope, electron-dense aggregates were seen in the gingival lamina propria,
      in the basement membrane and along the plasma membrane of the keratinocytes of
      the basal and spinous layers of the gingival and sulcular oral epithelia. In the
      junctional epithelium, Cuprolinic Blue-positive granules, 25 nm in diameter, were
      seen in the cytoplasm. Together with some vesicles containing electron-dense
      material, they may account for the staining process noted after
      autometallography. When the ultra-thin sections were digested with bovine
      testicular hyaluronidase, the staining was abolished. This indicates that
      glycosaminoglycans were primarily responsible for the staining pattern visualized
      with these methods. In the junctional epithelium, the cytosolic location of the
      25 nm granules reflects either transcellular transfer between the plasma membrane
      and the nucleus or accumulation of glycosaminoglycans in this group of
      keratinocytes. The glycoconjugates located inside vesicles or vacuoles are
      related to endocytosis and lysosomal degradation. Interstitial glycosaminoglycans
      seen in the two types of oral epithelium may play a role in the diffusion of
      water and nutriments.

PMID- 7515869
TI  - Differential surface characteristics of M cells from mouse intestinal Peyer's and
      caecal patches.
AB  - The mouse caecal patch is located near the blind end of the caecum, and consists
      of a group of lymphoid follicles. In common with the Peyer's patches, the
      follicle-associated epithelium overlying these follicles is largely composed of
      enterocytes, goblet cells and membranous epithelial (M) cells. Each of these
      types of cell was readily identified by electron microscopy, although caecal
      patch enterocytes and M cells were morphologically distinct from those of the
      Peyer's patches. Staining for alkaline phosphatase activity demonstrated that the
      majority of caecal follicle-associated epithelial cells were alkaline phosphatase
      negative, positive cells consisting of a mixture of enterocytes and M cells. In
      contrast, it has previously been found that Peyer's patch enterocytes are
      positive for alkaline phosphatase while the M cells are relatively lacking in
      alkaline phosphatase activity. Lectin histochemistry revealed that surface
      glycoconjugate expression differs between the caecal and Peyer's patch follicle
      associated epithelial cells; in particular, the characteristic staining of
      Peyer's patch M cells by Ulex europaeus agglutinin 1 was absent on the caecal
      patch follicle-associated epithelium. These altered surface characteristics
      indicate that the development of the caecal patch follicle-associated epithelial
      cells is influenced by the local environment, and these altered properties may be
      indicative of modified functional roles for the cells at this site.

PMID- 7515871
TI  - Detection and characterization of muscle-specific nuclear proteins.
AB  - To identify nuclear proteins related to muscle tissue specificity, we tried to
      prepare antibodies recognizing muscle-specific nuclear proteins. Taking advantage
      of the autoimmunity of some nuclear proteins, we prepared an antiserum against
      chick muscle nuclear proteins by injecting protein components of the nuclei
      isolated from chick breast muscles into breast muscle. Three proteins, named p30,
      p32, and p37, were detected with the antiserum in a two-dimensional SDS-PAGE
      pattern of the isolated nuclei. P30 and p32 were not detected in the nuclei of
      liver, brain, cardiac muscle, or slow type skeletal muscle (anterior latissimus
      dorsi). They were detected in those of fast type skeletal muscle (pectoralis
      major and semitendinosus) and smooth muscle (gizzard) at all developmental stages
      examined. On serial fractionation of muscle cell nuclei, they were detected in a
      fraction obtained after DNase I treatment of the sample, suggesting that the
      proteins weakly bind to chromatin. A homology search of amino acid sequences
      showed that there is no known protein similar to p32.

PMID- 7515873
TI  - Two sialidases which preferentially hydrolyze sialyl alpha 2-8 linkage from
      Bacteroides fragilis SBT3182.
AB  - Bacteroides fragilis SBT3182 produced two sialidases which differ in molecular
      weight on SDS-PAGE. These sialidases, a 50 kDa and a 55 kDa enzymes, were
      purified separately and their properties were compared. Both enzymes
      preferentially hydrolyze sialyl alpha 2-8 linkage rather than alpha 2-3 and alpha
      2-6 bonds. The Km values for Neu5Ac alpha 2-3lactose, Neu5Ac alpha 2-6lactose,
      and colominic acid, which is a homopolymer of N-acetylneuraminic acid linked by
      alpha 2-8 bonds, were identical between the two enzymes. These enzymes had Km
      value of 1.0-1.2 mM for Neu5Ac alpha 2-3lactose and 1.3-1.5 mM for Neu5Ac alpha 2
      6lactose, which are in the ranges reported for other sialidases. However, the Km
      values for colominic acid (0.03-0.04 mM) were lower than those of other
      sialidases, indicating that sialidases from B. fragilis SBT3182 show high
      affinity for the sialyl alpha 2-8 linkage. The two sialidases also had identical
      N-terminal amino acid sequences and did not reveal any homology to known
      sialidases. PAS-staining suggested that these two sialidases were glycoproteins.
      In the lectin analysis, the 50 kDa enzyme was stained with Con A, DBA, and UEA-I
      while the 55 kDa sialidase was stained only with Con A. This suggested that the
      difference in molecular weight may be due to the carbohydrate composition. When
      the 50 kDa enzyme was incubated with UEA-I, which is a lectin specific for alpha
      fucose residue, the activity decreased by 20%.

PMID- 7515870
TI  - The Pseudomonas aeruginosa algC gene encodes phosphoglucomutase, required for the
      synthesis of a complete lipopolysaccharide core.
AB  - We have constructed strains of Pseudomonas aeruginosa with mutations in the algC
      gene, previously shown to encode the enzyme phosphomannomutase. The algC mutants
      of a serotype O5 strain (PAO1) and a serotype O3 strain (PAC1R) did not express
      lipopolysaccharide (LPS) O side chains or the A-band (common antigen)
      polysaccharide. The migration of LPS from the algC mutant strains in Tricine
      sodium dodecyl sulfate-polyacrylamide gels was similar to that of LPS from a PAO1
      LPS-rough mutant, strain AK1012, and from a PAC1R LPS-rough mutant, PAC605, each
      previously shown to be deficient in the incorporation of glucose onto the LPS
      core (K. F. Jarrell and A. M. Kropinski, J. Virol. 40:411-420, 1981, and P. S. N.
      Rowe and P. M. Meadow, Eur. J. Biochem. 132:329-337, 1983). We show that, as
      expected, the algC mutant strains had no detectable phosphomannomutase activity
      and that neither algC strain had detectable phosphoglucomutase (PGM) activity. To
      confirm that the PGM activity was encoded by the algC gene, we transferred the
      cloned, intact P. aeruginosa algC gene to a pgm mutant of Escherichia coli and
      observed complementation of the pgm phenotype. Our finding that the algC gene
      product has PGM activity and that strains with mutations in this gene produce a
      truncated LPS core suggests that the synthesis of glucose 1-phosphate is
      necessary in the biosynthesis of the P. aeruginosa LPS core. The data presented
      here thus demonstrate that the algC gene is required for the synthesis of a
      complete LPS core in two strains with different LPS core and O side chain
      structures.

PMID- 7515872
TI  - Rat hepatic 3 alpha-hydroxysteroid dehydrogenase: expression of cDNA and
      physiological function in bile acid biosynthetic pathway.
AB  - 3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) [EC 1.1.1.213]2 plays
      important multifunctional roles in metabolizing steroid hormones, polycyclic
      aromatic hydrocarbons, and prostaglandins and also in transforming the steroid
      nucleus for the biosynthesis of bile acids from cholesterol in liver. To gain
      insight into the details and physiological functions of 3 alpha-HSD in the bile
      acid biosynthetic pathway, cDNA clones of 3 alpha-HSD were isolated from rat
      liver lambda phage cDNA libraries by using specific antibodies to 3 alpha-HSD
      purified from rat liver. Transfection of the 3 alpha-HSD cDNA in Simian COS7
      cells resulted in the expression of an immunoreactive protein to the antibodies
      against the purified enzyme, and the transfected cells exhibited activities for
      not only 7 alpha-hydroxy-5 beta-cholestan-3-one, the intermediate of bile acid
      biosynthesis, but also steroid hormones and 9,10-phenanthrenequinone. Northern
      blot analysis on poly(A)+ RNA by selective use of different cDNA fragments of the
      5'-untranslated region, the coding region, and the 3'-untranslated region as
      probes revealed three hybridizable bands, 3.6, 2.7, and 2.5 kb, in liver and four
      bands, 3.6, 2.7, 2.5, and 1.8 kb, in ovary. Of these, the 2.7- and 1.8-kb bands
      were predominant in liver and ovary, respectively. Northern hybridization
      analysis also revealed that the coding region of the various sizes of mRNA seemed
      to be common. Southern blot analysis of genomic DNA by the selective use of the
      cDNA fragments as probes indicated that the various mRNA species were derived
      from a single gene, probably due to an alternative splicing mechanism.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7515874
TI  - Transmembrane signal transduction by integrin cytoplasmic domains expressed in
      single-subunit chimeras.
AB  - Integrins are heterodimeric, transmembrane cell adhesion receptors that have
      recently been shown to function in transmembrane signal transduction. To examine
      the specific role of integrin intracellular domains in signal transduction,
      chimeric receptors containing various integrin intracellular domains coupled to a
      reporter consisting of the transmembrane and extracellular domains of the small,
      non-signaling subunit of the interleukin-2 receptor were expressed in cultured
      human fibroblasts and assayed for their ability to trigger tyrosine
      phosphorylation of the 125-kDa cytoplasmic tyrosine kinase, pp125FAK. Tyrosine
      phosphorylation of pp125FAK was induced in cultured fibroblasts that transiently
      expressed chimeric receptors containing either the beta 1, beta 3, or beta 5
      integrin intracellular domain and were selected by magnetic bead sorting.
      However, expression of chimeric receptors containing either the alpha 5 or an
      alternatively spliced form of the beta 3 intracellular domain (beta 3B), as well
      as those lacking an intracellular domain, failed to induce tyrosine
      phosphorylation of pp125FAK. These results indicate that information contained in
      the beta 1, beta 3, or beta 5 integrin intracellular domain is sufficient to
      stimulate integrin-mediated tyrosine phosphorylation of specific intracellular
      proteins and that integrin extracellular and transmembrane domains are not
      required for inducing tyrosine phosphorylation. Our results also indicate that
      alternative splicing can regulate the ability of beta integrin intracellular
      domains to participate in signal transduction, and they further suggest that the
      carboxyl-terminal region of specific beta integrins may play a role in the signal
      transduction pathway involving extracellular matrix molecules.

PMID- 7515875
TI  - Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide
      dependent activation of membrane-bound NO synthase in smooth muscle mediated by
      pertussis toxin-sensitive Gi1-2.
AB  - Plasma membranes isolated from dispersed gastric muscle cells exhibited
      calmodulin-dependent NOS activity that was stimulated by Ca2+ in the range 0.1-1
      mM (maximum 10 microM). Vasoactive intestinal peptide (VIP) and pituitary
      adenylate cyclase-activating peptide (PACAP) (in the presence of GTP), and GTP
      gamma S (guanosine 5'-O-(gamma-thio)triphosphate) stimulated NOS activity in a
      concentration-dependent fashion above that maximally stimulated by Ca2+. The
      increase in NOS activity induced by VIP, PACAP, and GTP gamma S was abolished by
      GDP beta S (guanosine 5'-O-(beta-thio)diphosphate), which had no effect on NOS
      activity stimulated by Ca2+. The NOS inhibitor NG-nitro-L-arginine and the
      calmodulin antagonist calmidazolium abolished NOS activity stimulated by all
      agents including Ca2+. NOS activity stimulated by GTP gamma S, VIP, and PACAP was
      inhibited by Gi alpha 1-2 antibody but not by Gq alpha, Gs alpha, and Gi alpha 3
      antibodies. NOS activity stimulated by VIP and PACAP was inhibited by 80-83% in
      membranes derived from pertussis toxin-treated cells. We conclude that a
      Ca2+/calmodulin-dependent NOS present in plasma membranes of gastric muscle cells
      is activated by two homologous peptide transmitters, VIP and PACAP, via a common
      receptor coupled to pertussis toxin (PTx)-sensitive Gi1-2. The study provides the
      first evidence of receptor-mediated G protein activation of NOS in smooth muscle
      cells.

PMID- 7515876
TI  - Cation sensitivity of inositol 1,4,5-trisphosphate production and metabolism in
      agonist-stimulated adrenal glomerulosa cells.
AB  - Angiotensin II (AII) evokes a biphasic increase in inositol 1,4,5-trisphosphate
      (Ins(1,4,5)P3) levels in adrenal glomerulosa cells, with an extracellular Ca(2+)
      independent early peak followed by a secondary sustained elevation that is highly
      dependent on the presence of extracellular Ca2+. The Ca(2+)-dependent sustained
      phase of agonist-induced Ins(1,4,5)P3 production was closely correlated with Ca2+
      influx and was inhibited by inorganic Ca2+ channel blockers with the potency
      ratio: La3+ >> Cd2+ > Mn2+ > Co2+ > Ni2+. Of the two Ca2+ surrogates, Sr2+ and
      Ba2+, Sr2+ was partially active compared with Ca2+, and Ba2+ was inactive in
      restoring Ins(1,4,5)P3 formation in cells stimulated with AII in Ca(2+)-free
      medium. However, unlike Ca2+, Sr2+ only weakly supported and Ba2+ failed to
      affect the calmodulin-activation of Ins(1,4,5)P3 3-kinase. Also, there was an
      accumulation of Ins(1,4,5)P3 and diminished formation of Ins(1,3,4,5)P4 and
      Ins(1,3,4)P3 when intact glomerulosa cells were stimulated by AII in the presence
      of Sr2+. This difference between the Sr2+ sensitivity of phospholipase C and
      Ins(1,4,5)P3 3-kinase provides a means for the potentiation of agonist-induced
      elevations of Ins(1,4,5)P3 in the intact cell and for direct analysis of the role
      of the inositol tris-/tetrakisphosphate pathway in cellular signaling.

PMID- 7515877
TI  - Regulatory role of major tyrosine autophosphorylation site of kinase domain of c
      Met receptor (scatter factor/hepatocyte growth factor receptor).
AB  - Ligand-induced tyrosine kinase activation of the scatter factor/hepatocyte growth
      factor receptor (c-Met) is thought to be essential for the biological responses
      of target cells. To assess the regulatory role of the major tyrosine
      autophosphorylation site (tyrosine 1233) of the mouse c-Met receptor in the
      tyrosine kinase activation of the receptor, we constructed a mutant receptor in
      which the tyrosine residue was replaced with phenylalanine. When the cells
      expressing the mutant receptor were incubated with the ligand, no biological
      responses were observed, and the level of tyrosine phosphorylation of the
      receptor was very low compared with that of the wild-type receptor. The in vitro
      kinase activity of the mutant receptor toward an exogenous substrate and the
      receptor itself was also low. Furthermore, tyrosine phosphorylation of the
      cellular proteins by ligand stimulation was not detected in intact cells
      expressing the mutant receptor. The low level of kinase activity and the lack of
      biological activity of the mutant receptor indicate that the major
      autophosphorylation site positively regulates the tyrosine kinase of the c-Met
      receptor and phosphorylation of cellular substrates in the scatter
      factor/hepatocyte growth factor signaling pathway.

PMID- 7515878
TI  - Activation of myosin light chain kinase and nitric oxide synthase activities by
      calmodulin fragments.
AB  - We have investigated the abilities of calmodulin (CaM) tryptic fragments 1-75
      (TRCI) or 78-148 (TRCII) to activate gizzard smooth muscle myosin light chain
      kinase (gMLCK), rabbit skeletal muscle myosin light chain kinase (skMLCK), and
      neural nitric oxide synthase (nNOS) activities. Our results indicate for all
      three enzymes that binding of CaM follows an ordered mechanism wherein the C
      terminal lobe, represented by TRCII, binds specifically to a site we designated
      as A, followed by binding of the N-terminal lobe, represented by TRCI, to a site
      designated as B. With TRCII and TRCI bound to their respective sites, skMLCK and
      gMLCK activities are both activated to about 80% of their maximum levels.
      Occupancy of both sites in the MLCK enzymes by TRCI results in only low levels of
      enzyme activation; occupancy of both sites by TRCII also results in low levels of
      gMLCK activity, but activates skMLCK activity to 65% of the maximum level. With
      TRCI bound at site B and either TRCII or TRCI bound at site A, nNOS activity is
      50% of the maximum level. Apparent dissociation constants for TRCII binding to
      site A and TRCI binding to site B are, respectively; 0.3 and 3 microM (skMLCK);
      1.2 and 0.8 microM (gMLCK); 10 nM and 150 microM (nNOS). Our results demonstrate
      that the CaM lobes can make distinct contributions to binding and/or activation
      of different CaM-dependent enzymes and that the tethering function of the central
      helix can be mimicked by sufficiently high concentrations of the CaM fragments.
      We have modeled tethering as if it stabilizes the CaM-enzyme complex by creating
      a high effective concentration of the N-terminal lobe. Calculated values for this
      concentration term indicate essentially identical contributions by the central
      helix to the observed nanomolar dissociation constants of the three CaM-enzyme
      complexes examined.

PMID- 7515879
TI  - Signaling by the cytoplasmic domain of hematopoietin receptors involves two
      distinguishable mechanisms in hepatic cells.
AB  - The receptor for granulocyte colony stimulating factor (G-CSFR) and chimeric
      receptors consisting of the extracellular domain of G-CSFR and the transmembrane
      and cytoplasmic domain of the leukemia inhibitory factor receptor, gp130, or c
      mpl function as homodimeric complexes. These receptors mediate a similar
      stimulation of gene transcription via separate regulatory elements of acute phase
      plasma protein genes. To identify the receptor regions within the cytoplasmic
      domains necessary for transcriptional regulation, the receptors were transiently
      expressed in rat hepatoma cells. Each receptor form reconstituted G-CSF-induced
      expression of a chloramphenicol acetyltransferase gene construct containing the
      cytokine response element of the rat alpha 1-acid glycoprotein gene. This
      regulation required the presence of two conserved sequence motifs (referred to as
      box 1 and box 2) in the cytoplasmic domains of each receptor. With the exception
      of G-CSFR-MPL chimera, the receptors also mediated a similarly high stimulation
      via the IL-6 response element of the rat beta-fibrinogen and hemopexin genes.
      Regulation of the IL-6 response element required, however, in addition to boxes 1
      and 2, a third sequence motif (box 3). This motif is absent in the cytoplasmic
      domain of c-mpl, possibly explaining its inability to activate the IL-6 response
      element. When cells which express receptor forms with prominent box 3 function
      were treated with suramin, a ligand-independent gene stimulation via the IL-6
      response element was observed. The suramin effect probably involves a receptor
      dimerization mediated by the extracellular G-CSFR domain and by the intracellular
      regions that include box 3.

PMID- 7515881
TI  - The voltage sensor of the mitochondrial permeability transition pore is tuned by
      the oxidation-reduction state of vicinal thiols. Increase of the gating potential
      by oxidants and its reversal by reducing agents.
AB  - Reaction of isolated mitochondria with a variety of agents that lead to oxidation
      or cross-linking of sulfhydryl groups leads to an increased "open" probability of
      the permeability transition pore, a cyclosporin A-sensitive channel. We have
      investigated the mechanism by which the pore is induced by menadione, diamide,
      arsenite, and tert-butylhydroperoxide. We find that these inducers increase the
      probability of pore opening by shifting its gating potential to higher values.
      Furthermore, the induced shift was prevented by treatment with N-ethylmaleimide
      or dithiothreitol. At moderate levels of depolarization an apparent I50 for N
      ethylmaleimide of bout 5 microM can be defined, while the N-ethylmaleimide or
      dithiothreitol effects are overcome by maximal depolarization. We conclude that
      the oxidation-reduction state of vicinal thiols in cysteinyl residues plays a
      critical role in tuning the voltage sensor of the transition pore, with an
      increase of gating potential (i.e. an increase in the probability of pore opening
      despite a high transmembrane potential difference) as the couple is poised to a
      more oxidized state. These findings may have implications for the mechanism of
      cell damage under oxidative stress.

PMID- 7515880
TI  - TRAP, the trp RNA-binding attenuation protein of Bacillus subtilis, is a
      multisubunit complex that appears to recognize G/UAG repeats in the trpEDCFBA and
      trpG transcripts.
AB  - A filter binding assay was developed to study interactions between purified TRAP,
      the trp RNA-binding attenuation protein of Bacillus subtilis, and trp specific
      transcripts. TRAP formed stable complexes with trpEDCFBA leader RNA; binding was
      L-tryptophan-dependent and was complete within 60 s. TRAP binds to a segment of
      the trp leader transcript that includes part of an RNA antiterminator structure.
      Binding to this segment allows formation of an RNA terminator structure, thereby
      promoting transcription termination. Using several trpEDCFBA leader deletion
      transcripts, we identified several closely spaced trinucleotide repeats (seven
      GAG and four UAG repeats) in the trp leader transcript that appeared to be
      required for TRAP binding. We also showed that TRAP binds to a segment of the
      trpG transcript that includes the trpG ribosome binding site; the nucleotide
      sequence of this segment contains several appropriately spaced trinucleotide
      repeats (seven GAG, one UAG, and one AAG). TRAP binding to the trpG transcript
      would block translation initiation. RNA footprint analysis confirmed interaction
      between TRAP and the trinucleotide repeats in the various transcripts. TRAP, in
      the presence or absence of L-tryptophan, appears to consist of 11 or 12 identical
      8-kDa subunits. Our findings suggest that each tryptophan-activated TRAP subunit
      can bind one G/UAG repeat in a target transcript. Multiple protein-RNA
      interactions are required for stable association.

PMID- 7515882
TI  - Stimulation of protein phosphatase-1 activity by phorbol esters. Evaluation of
      the regulatory role of protein kinase C in insulin action.
AB  - In this study, we examined the role of insulin, protein kinase C (PKC) and
      mitogen-activated protein kinase (MAPK) cascade in activation of protein
      phosphatase-1 (PP-1) by using three complementary approaches. First,
      differentiated L6 cells were acutely exposed to 12-O-tetradecanoylphorbol-13
      acetate (TPA, 400 nM) to activate PKC. In these cells, TPA caused 32% stimulation
      of PP-1 activity. The PP-1 stimulation by TPA was comparable to stimulation by
      insulin (t1/2 = 1 min and EC50 = 5 nM) with a maximum effect in 5 min. The
      effects of insulin and TPA were not additive. Insulin and TPA also stimulated
      MAPK (> 2-fold increase over basal, with myelin basic protein as a substrate). ML
      9, a myosin light chain kinase inhibitor, blocked the effects of insulin and TPA
      on both MAPK and PP-1 activation. In the second approach, PKC was down-regulated
      by chronic treatment with TPA. In these cells subsequent effects of insulin on
      MAPK and PP-1 activation were blocked, without an effect on basal enzyme levels.
      In the third approach, two selective inhibitors of PKC, calphostin and
      chelerythrine chloride, were used to inhibit PKC. These inhibitors completely
      prevented insulin and TPA stimulation of MAPK and PP-1 and blocked insulin
      induced translocation of PKC to the plasma membranes. We conclude that PKC plays
      an important role in insulin stimulation of PP-1 via the activation of MAPK
      cascade.

PMID- 7515883
TI  - Interaction of Clostridium botulinum C2 toxin with lipid bilayer membranes.
      Formation of cation-selective channels and inhibition of channel function by
      chloroquine.
AB  - Lipid bilayer experiments were performed with the C2-II binding component of the
      ADP-ribosylating C2 toxin from Clostridium botulinum. The trypsin-activated but
      not the nonactivated form of the protein was able to increase the specific
      conductance of artificial lipid bilayer membranes by the formation of ion
      permeable channels. The channels had on average a single-channel conductance of
      55 pS in 0.1 M KCl and were found to be cation-selective and voltage-dependent.
      The single-channel conductance was only moderately dependent on the bulk aqueous
      KCl concentration, which indicated point charge effects on the channel
      properties. Incubation of the activated C2-II binding component with antibodies
      against C2-II or with C2-I toxin inhibited channel formation to a large extent.
      Addition of chloroquine, a known inhibitor of endocytosis in cells, led to a dose
      dependent decrease of the C2-II-induced membrane conductance. This result
      suggested that the activated C2-II component contains a binding site for
      chloroquine inside the channel. It is discussed that the channels formed by C2-II
      component are involved in the translocation of C2-I toxin across the target cell
      membrane.

PMID- 7515884
TI  - Steel factor stimulates the serine/threonine phosphorylation of the interleukin-3
      receptor.
AB  - The murine interleukin-3 (IL-3) dependent cell line, B6SUtA1, which expresses
      high IL-3 receptor (IL-3R) numbers, was found to proliferate in a greater than
      additive fashion when grown in the presence of IL-3 and steel factor (SF).
      However, pretreatment of these cells with SF had no effect on the number of IL
      3Rs expressed at the cell surface nor their affinity for IL-3. Interestingly,
      although, SF did induce the rapid and transient serine- and threonine-specific
      phosphorylation of the beta IL-3 subunit of the IL-3R. This serine/threonine
      phosphorylation was also observed with the phorbol ester, 12-O
      tetradecanoylphorbol-13-acetate, and both the 12-O-tetradecanoylphorbol-13
      acetate- and SF-induced phosphorylation of the IL-3R could be inhibited with the
      highly specific protein kinase C inhibitor, bisindolylmaleimide (Compound 3),
      suggesting that SF might be stimulating this phosphorylation via protein kinase
      C. This SF-induced phosphorylation also occurred within 10 min of incubation at 4
      degrees C, indicating that this might be a relatively early event in the c-kit
      signaling pathway. Last, this SF-induced phosphorylation of the IL-3R occurred in
      the presence of the tyrosine kinase inhibitor, genistein, at levels which blocked
      the autophosphorylation of c-kit. This suggests that c-kit might be capable of
      mediating this cross-talk phenomenon in the absence of its endogenous tyrosine
      kinase activity.

PMID- 7515887
TI  - Activation of protein tyrosine kinase p72syk by Fc epsilon RI aggregation in rat
      basophilic leukemia cells. p72syk is a minor component but the major protein
      tyrosine kinase of pp72.
AB  - Aggregation of the high affinity IgE receptors (Fc epsilon RI) on rat basophilic
      leukemia RBL-2H3 cells results in protein tyrosine phosphorylations. Previously
      we reported that there is prominent tyrosine phosphorylation of approximately 72
      kDa proteins (pp72) and that the tyrosine kinase p72syk is one component of pp72.
      Here we studied further the relationship of p72syk to pp72. The aggregation of Fc
      epsilon RI induced the activation of p72syk which was parallel to its tyrosine
      phosphorylation. By in vitro kinase assay of immune complexes purified with anti
      phosphotyrosine antibodies, p72syk was the major pp72 tyrosine kinase. However,
      by immunoblotting with anti-phosphotyrosine antibodies, p72syk was a minor
      component of pp72. The heterogeneous nature of pp72 was indicated by different
      studies. Under optimum conditions of one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, pp72 consisted of a heterogeneous group of 69
      , 71-, and 72-kDa tyrosine-phosphorylated proteins. There were differences in the
      tyrosine phosphorylation of these proteins in cells activated in the absence of
      extracellular calcium or when stimulation was with the calcium ionophore A23187
      or with phorbol myristate acetate. One of the proteins migrating at 69 kDa was
      p72syk. By two-dimensional gel electrophoresis pp72 was found to consist of
      multiple tyrosine-phosphorylated protens including 71-80-kDa proteins that
      associate with p53/56lyn. A 75-kDa tyrosine-phosphorylated protein, different
      from pp72, was identified as p75HS1 (SPY75). These results demonstrate the
      heterogeneous nature of the pp72 and that p72syk is activated after Fc epsilon RI
      aggregation.

PMID- 7515885
TI  - Differential expression of a novel protein kinase in human B lymphocytes.
      Preferential localization in the germinal center.
AB  - B lymphocytes which reside in the germinal center region of lymphoid follicles
      are functionally and phenotypically distinct from the surrounding mantle zone B
      cells. We have isolated cDNA clones for several genes that are differentially
      expressed between these two populations of B lymphocytes. One such gene, BL44, is
      preferentially expressed in germinal center B cells. The nucleotide sequence of a
      2,874-base pair BL44 cDNA was determined and a 2,451-bp open reading frame found
      that encodes for a 97-kDa serine/threonine protein kinase referred to as GC
      kinase. It has an NH2-terminal catalytic domain most similar to that of the
      Drosophila NinaC protein and the yeast STE20 protein. GC kinase mRNA transcripts
      are not unique to germinal center B cells and are found in several other tissues,
      including brain, lung, and placenta. The GC kinase protein was immunoprecipitated
      from transfected COS cells and from the Burkitt cell line RAMOS. GC kinase
      immunoprecipitated from transfected COS cells phosphorylated the substrates
      casein and myelin basic protein. In addition, a 97-kDa phosphoprotein likely to
      be GC kinase itself was detected. GC kinase may participate in an important
      signal transduction pathway in germinal center B cells.

PMID- 7515886
TI  - Identification of chemoattractant receptors and G-proteins in the vomeronasal
      system of garter snakes.
AB  - Garter snakes respond to purified chemoattractants derived from prey. The
      specific binding sites for one of these chemoattractants, ES20, in the
      vomeronasal organ was saturable and reversible. Binding sites for ES20 were
      abolished by heating or greatly reduced by Pronase digestion. ES20
      chemoattractant activity and receptor binding required Ca2+. Binding of ES20 to
      sensory epithelium derived from animals with bipolar neurons depleted by
      denervation was reduced 22-43% as compared to control animals. However, there was
      an upregulation of the ES20 receptor population in the nonsensory cells following
      nerve cuts. Three G-proteins (Gs, Gi, and G(o)) were tentatively identified using
      immunoreactivity and ADP-ribosylation techniques. Gi and G(o) proteins were shown
      to be coupled with ES20-receptor and effectors as evidenced by: 1) the affinity
      of ES20-receptor was decreased by GTP gamma S; 2) ES20-receptor binding caused a
      reduction in ADP-ribosylation of pertussis toxin-susceptible G-proteins, and the
      inhibitory effect of ES20-receptor on ADP-ribosylation was attenuated by GDP beta
      S; 3) the effect of ES20-receptor on ADP-ribosylation of the pertussis toxin
      susceptible G-proteins could be mimicked by G-protein activators, such as GTP
      gamma S or AlF3; 4) ES20-receptor binding resulted in a decrease of the basal
      level of cAMP; 5) the binding of ES20 to its receptors caused an increase in the
      level of D-myo-inositol 1,4,5-trisphosphate.

PMID- 7515888
TI  - In migrating fibroblasts, recycling receptors are concentrated in narrow tubules
      in the pericentriolar area, and then routed to the plasma membrane of the leading
      lamella.
AB  - By following the intracellular processing of recycling transferrin receptors and
      the selective sorting of a-2 macroglobulin in chick embryo fibroblasts, we have
      shown that the concentration of 60 nm diam tubules which surrounds the centrioles
      represents a distal compartment on the recycling pathway. In migrating cells
      transferrin receptor tracers can be loaded into this compartment and then chased
      to the cell surface. When they emerge the recycling transferrin receptors are
      distributed over the surface of the leading lamella.

PMID- 7515889
TI  - Structural requirements for adhesion of soluble recombinant murine vascular cell
      adhesion molecule-1 to alpha 4 beta 1.
AB  - This study describes the identification of seven amino acid residues of the
      vascular cell adhesion molecule (VCAM-1) that influence binding to the alpha 4
      beta 1 receptor. Using recombinant murine VCAM-1-IgG, which is bound by both
      mouse (WEHI 231) and human (Ramos) lymphoid cells, two approaches demonstrated
      the crucial role of the first two NH2-terminal Ig-like domains in binding: (a)
      blocking monoclonal anti-mouse VCAM-1 antibodies bound to only truncation
      variants that included the first two domains; (b) site-direct mutagenesis of the
      first NH2-terminal domain showed that alanine substitution of the amino acid
      residues R36, D40, K46, S54, N65, T72, and E81 partially or completely reduced
      adherence by human and/or mouse cells. Of these D40, when mutated to A, N, or K
      (but not E), showed complete abrogation of adherence by mouse and human cells, as
      well as inability to bind blocking anti-murine VCAM-1 antibody MVCAM.A429, while
      not inducing gross structural perturbations in VCAM-1. By molecular modeling, the
      D40 residue was located on a beta turn connecting two beta strands defined as C
      and D. The residues R36, K46, S54, N65, T72, and E81, which perturb cell
      adherence and caused small changes to gross structure, are conformationally near
      or adjacent to D40. Although these residues, identified as crucial for cell
      adhesion, are all located in domain 1, it is evident that there is a structural
      requirement for domains 1 and 2 to be intact so that cell adhesive function can
      occur.

PMID- 7515890
TI  - CR3 (Mac-1, alpha M beta 2, CD11b/CD18) and Fc gamma RIII cooperate in generation
      of a neutrophil respiratory burst: requirement for Fc gamma RIII and tyrosine
      phosphorylation.
AB  - Cooperation among plasma membrane receptors in activating signal transduction
      cascades is not well understood. For almost 20 years, it has been clear that when
      a particulate foreign body is opsonized with complement as well as IgG, the
      efficiency of IgG effector functions is markedly enhanced. However, the molecular
      mechanisms involved in cooperation between IgG Fc receptors and complement
      receptors have not been elucidated. In this work, we show that when human
      neutrophils (PMN) are plated on a surface coated with both anti-CR3 and anti-Fc
      gamma RIII antibodies, the respiratory burst which occurs is equivalent to that
      stimulated by anti-Fc gamma RII. The CR3 ligand iC3b is as effective as anti-CR3
      for cooperating with anti-Fc gamma RIII in generation of a respiratory burst. The
      synergy between CR3 and Fc gamma RIII for activating the NADPH oxidase is
      abolished by Fab of anti-Fc gamma RII. Nonetheless, the observed synergy is not
      an artifact of unintended Fc gamma RII ligation, since (a) only this combination
      of antibodies works to generate H2O2; (b) coating plates with either of the
      antibodies alone cannot activate the respiratory burst at any dose; (c) LAD (CR3
      deficient) cells, which are perfectly competent to mount a respiratory burst when
      Fc gamma RII is engaged, are incapable of activating the respiratory burst when
      adherent to wells coated with anti-Fc gamma RIII and anti-CR3; (d) direct
      engagement of Fc gamma RII activates the respiratory burst by a pathway
      pharmacologically distinguishable from the synergistic respiratory burst. Fc
      gamma RIII/CR3 synergy is abolished by cytochalasin B and herbimicin, suggesting
      that both the actin cytoskeleton and tyrosine phosphorylation are necessary for
      activation of the synergistic respiratory burst. Further analysis shows that CR3
      and Fc gamma RIII have distinct roles in activation of this Fc gamma RII
      dependent assembly of the NADPH oxidase. Ligation of CR3 is sufficient to lead to
      Fc gamma RII association with the actin cytoskeleton on the adherent PMN surface.
      Coligation of Fc gamma RIII is required for tyrosine phosphorylation of Fc gamma
      RII. These data are consistent with a model in which phosphorylation of Fc gamma
      RII or a closely associated substrate initiates activation of a signal
      transduction pathway leading to oxidase assembly. These are the first data to
      demonstrate a molecular mechanism for synergy between IgG Fc and complement
      receptors in activation of phagocyte effector functions.

PMID- 7515892
TI  - Developmental expression of mucin genes MUC1 and MUC2.
AB  - The mucin gene MUC1, is expressed in a number of human ductal epithelia in vivo
      including those within the pancreas, mammary gland, kidney and genital ducts.
      Further it is expressed at a high level in certain tumours and tumour-derived
      cell lines. MUC2 was initially isolated from a human jejunum cDNA library and is
      thought to be one of the major intestinal mucin genes, though it is also
      expressed in the trachea. We have examined the developmental expression of these
      two mucin genes in human tissues. High level expression of MUC1 has been seen by
      12.5 weeks of gestation in the epithelial of the distal respiratory tract and the
      collecting ducts in the kidney. By 18 weeks MUC1 mRNA is detectable in the colon
      but pancreatic expression of MUC1 is not seen until late in gestation. MUC2 mRNA
      is seen by 12 weeks of gestation in the jejunum, ileum and colon, and in large
      bronchioles of the lung by 18 weeks. The pattern of expression of MUC1 suggests
      that this mucin may not be involved in early ductal obstruction in the CF
      pancreas, but both MUC1 and MUC2 may play a role in the development of intestinal
      disease and MUC1 in early respiratory disease associated with CF.

PMID- 7515893
TI  - Replication and transcription sites are colocalized in human cells.
AB  - HeLa cells synchronized at different stages of the cell cycle were permeabilized
      and incubated with analogues of nucleotide triphosphates; then sites of
      incorporation were immunolabeled with the appropriate fluorescent probes.
      Confocal microscopy showed that sites of replication and transcription were not
      diffusely spread throughout nuclei, reflecting the distribution of euchromatin;
      rather, they were concentrated in 'foci' where many polymerases act together.
      Transcription foci aggregated as cells progressed towards the G1/S boundary;
      later they dispersed and became more diffuse. Replication was initiated only at
      transcription sites; later, when heterochromatin was replicated in enlarged foci,
      these remained sites of transcription. This illustrates the dynamic nature of
      nuclear architecture and suggests that transcription may be required for the
      initiation of DNA synthesis.

PMID- 7515891
TI  - Monocyte rolling, arrest and spreading on IL-4-activated vascular endothelium
      under flow is mediated via sequential action of L-selectin, beta 1-integrins, and
      beta 2-integrins.
AB  - Leukocyte interactions with vascular endothelium at sites of inflammation can be
      dynamically regulated by activation-dependent adhesion molecules. Current models,
      primarily based on studies with polymorphonuclear leukocytes, suggest the
      involvement of multiple members of the selectin, integrin, and immunoglobulin
      gene families, sequentially, in the process of initial attachment (rolling),
      stable adhesion (arrest), spreading and ultimate diapedesis. In the current
      study, IL-4-activated human umbilical vein endothelium, which selectively
      expresses VCAM-1 and an L-selectin ligand but not E-selectin, and appropriate
      function blocking monoclonal antibodies, were used to study monocyte-endothelial
      interactions in an in vitro model that mimics microcirculatory flow conditions.
      In this system, L-selectin mediates monocyte rolling and also facilitates alpha 4
      beta 1-integrin-dependent arrest, whereas beta 2-integrins are required for
      spreading of firmly attached monocytes on the endothelial cell surface but not
      their arrest. These findings provide the first in vitro evidence for human
      monocyte rolling on cytokine-activated endothelium, and suggest a sequential
      requirement for both beta 1- and beta 2-integrin-dependent adhesive mechanisms in
      monocyte-endothelial interactions.

PMID- 7515894
TI  - Analysis of HPV16 E6 and mutant p53-transfected keratinocytes in reconstituted
      epidermis suggests that wild-type p53 inhibits cytokeratin 19 expression.
AB  - Using a reconstituted skin culture model we have analysed the effects of
      oncogenic human papillomavirus (HPV) and mutant TP53 genes on the proliferation
      and differentiation of human keratinocytes. Immortal cell lines generated by
      transfection of early passage normal human keratinocytes with HPV16 E7 plus
      mutant human TP53 (KN #1), HPV16 E7/E6 (KN #2), or HPV16 E7 plus murine p53 (KN
      #3) were examined. KN #1 and KN #2 behaved identically, reconstructing a tumor
      like epidermis characterized by the lack of differentiation and the presence of
      an aberrant epidermal architecture. In contrast, KN #3 reconstructed an epidermis
      that was more similar to that obtained with normal keratinocytes. KN #1 and KN #2
      were further characterized by the inversion of the proliferative compartment and
      the abnormal expression of cytokeratin 19 (CK19). Because p53 function is reduced
      in these cells, either by heterocomplex formation between endogenous wild-type
      p53 and transfected mutant p53 or by E6-induced degradation of wild-type p53, we
      hypothesized that CK19 expression may be normally repressed by wild-type p53.
      This hypothesis was supported by the strict correlation observed between TP53
      mutation and CK19 expression in a set of human skin tumors. CK19 was detected in
      all eight carcinomas containing a mutated TP53 gene but in none of the 16
      carcinomas containing only wild-type TP53. These results illustrate the utility
      of the in vitro reconstituted skin model for investigating the consequences of
      genetic alterations in human keratinocytes.

PMID- 7515895
TI  - Extracellular ATP triggers two functionally distinct calcium signalling pathways
      in PC12 cells.
AB  - We have investigated the effects of extracellular ATP on Ca2+ signalling, and its
      relationship to secretion in rat pheochromocytoma (PC12) cells. In single cells,
      extracellular ATP evoked two very distinct subcellular distributions of
      intracellular calcium concentration ([Ca2+]i), only one of which could be
      mimicked by the pyrimidine nucleotide UTP, suggesting the involvement of more
      than one cell surface receptor in mediating the ATP-induced responses. ATP and
      UTP were equipotent in activating a receptor leading to inositol phosphate
      production and the mobilisation of intracellular Ca2+. In some cells (19%) this
      rise in [Ca2+]i initiated at a discrete site and then propagated across the cell
      in the form of a Ca2+ wave. In addition to mobilising intracellular Ca2+ through
      a 'nucleotide' receptor sensitive to ATP and UTP, the results indicate that ATP
      also activates divalent cation entry through an independent receptor-operated
      channel. Firstly, ATP-induced entry of Ca2+ or Mn2+ was independent of Ca2+
      mobilisation, as prior treatment of cell populations with UTP abolished the ATP
      evoked release of intracellular Ca2+ stores, but left the Ca(2+)- and Mn(2+)
      entry components uneffected. Secondly, although UTP and ATP were equally
      effective in generating inositol phosphates, only ATP stimulated divalent cation
      entry, indicating that ATP-activated influx was independent of phosphoinositide
      turnover. Thirdly, single cell experiments revealed a subpopulation of cells that
      responded to ATP with divalent cation entry without mobilising Ca2+ from
      intracellular stores. Lastly, the dihydropyridine antagonist, nifedipine, reduced
      the ATP-induced rise in [Ca2+]i by only 24%, suggesting that Ca2+ entry was
      largely independent of L-type voltage-operated Ca2+ channels. The Ca2+ signals
      could also be distinguished at a functional level. Activation of ATP-induced
      divalent cation influx was absolutely required to evoke transmitter release,
      because ATP triggered secretion of [3H]dopamine only in the presence of external
      Ca2+, and UTP was unable to promote secretion, irrespective of the extracellular
      [Ca2+]. The results suggest that the same extracellular stimulus can deliver
      different Ca2+ signals into the same cell by activating different Ca2+ signalling
      pathways, and that these Ca2+ signals can be functionally distinct.

PMID- 7515896
TI  - Induction of human tenascin (neuronectin) by growth factors and cytokines: cell
      type-specific signals and signalling pathways.
AB  - The extracellular matrix protein tenascin (TN) is expressed with precise temporo
      spatial patterns during embryonic and fetal development and is induced in healing
      wounds, inflammatory lesions and solid tumors. These tissue patterns suggest that
      TN synthesis may be modulated by soluble factors present in developing tissues or
      released from injured, inflammatory or neoplastic cells. To characterize the
      extrinsic control of human TN we examined the effects of several signalling
      molecules on cultured neural, melanocytic and fibroblastic cells. Results
      obtained with alpha TN antibodies in enzyme-linked immunosorbent and
      immunoprecipitation assays indicate that TN expression is tightly regulated in a
      cell type-specific manner: (1) Primitive neuroectodermal tumor (PNET) cells grown
      in chemically defined, serum-free media show up to > 100-fold TN induction in
      response to fibroblast growth factors (aFGF, bFGF, K-FGF) and phorbol ester,
      independent of changes in cell proliferation or total protein synthesis; no
      induction is seen in PNET cultures stimulated with serum or other growth and
      differentiation factors. (2) Normal melanocytes, which require FGF and phorbol
      ester for survival in vitro, fail to express TN; however, they produce TN
      following oncogenic transformation. (3) Fibroblasts derived from disparate
      tissues differ up to 100-fold in basal TN production; for example, fetal lung
      fibroblasts are TNhigh, but conjunctival fibroblasts derived from the same donors
      and fetal leptomeningeal cells are TNlow. (4) TNlow fibroblasts treated with
      interleukin-1, tumor necrosis factor-alpha, and interleukin-4 show up to > 100
      fold increased TN secretion and TN incorporation into their extracellular matrix.
      Transforming growth factor-beta, which acts as an inducer of fibronectin,
      collagen, and integrin-type matrix receptors, has variable effects on fibroblast
      TN, ranging from increased deposition in the extracellular matrix of fetal
      conjunctival fibroblasts to reduced secretion in newborn foreskin fibroblasts. In
      contrast, FGFs (which are potent fibroblast mitogens), phorbol ester, bone
      morphogenetic proteins, and several other factors tested produced no discernible
      effects on fibroblast TN expression. These findings suggest that discrete sets of
      extrinsic signals modify TN expression in specific cell types, with the effects
      of a given ligand/receptor system determined by cell type-specific signalling
      pathways that may be linked to unique cis-regulatory elements of the TN gene. As
      a result, a limited set of regulatory peptides may produce highly diversified TN
      distribution patterns in developing and lesional tissues.

PMID- 7515897
TI  - Integrin expression and localization in normal MDCK cells and transformed MDCK
      cells lacking apical polarity.
AB  - Epithelial cells polarize in response to contacts with the extracellular matrix
      and with neighboring cells. Interactions of cells with the extracellular matrix
      are mediated mainly by the integrin family of receptors. To begin to understand
      the role of integrins in polarization, we have investigated the expression and
      localization of three integrin families in the polarized Madin-Darby canine
      kidney (MDCK) epithelial cell line and in transformed MDCK cells lacking apical
      polarity. We find that MDCK cells express several beta 1 integrins, including
      alpha 2 beta 1, alpha 3 beta 1, and an unidentified integrin designated alpha x
      beta 1. The beta 1 integrins are the major receptors for collagens I and IV and
      laminin in MDCK cells, since a blocking anti-beta 1 antibody almost totally
      abolishes adhesion to these proteins. They also express a vitronectin receptor
      tentatively identified as alpha v beta 3, and the epithelial-specific integrin
      alpha 6 beta 4. The latter is not a laminin receptor in MDCK cells because a
      function blocking anti-alpha 6 antibody has no effect on cell adhesion to
      laminin. All three integrin families are expressed exclusively on both the basal
      and lateral surfaces, as determined by immunofluorescence microscopy and surface
      biotinylation. Transformed MDCK cells express beta 1 integrins as well as alpha v
      beta 3 and alpha 6 beta 4, but show alterations in the beta 1 family. Expression
      of alpha x is lacking, and the relative amount of the beta 1 subunit is
      diminished, resulting in the accumulation of Endo-H-sensitive alpha 3. In
      addition, surface biotinylation and immunofluorescence indicate that significant
      amounts of both alpha 2 beta 1 and alpha 3 beta 1 appear on not only the
      basolateral but also the apical plasma membrane. These results indicate that
      integrins are the major receptors for the extracellular matrix in MDCK cells, and
      that they may affect epithelial cell polarization by mediating not only cell
      substratum but also cell-cell contacts.

PMID- 7515898
TI  - Affinity studies of human anti-MAG antibodies in neuropathy.
AB  - Human IgM anti-myelin associated glycoprotein (MAG) antibodies from patients with
      neuropathy bind to oligosaccharide determinants shared by MAG and several other
      glycoconjugates in peripheral nerve. The apparent affinities of human anti-MAG
      antibodies were determined by an ELISA system which measures free antibody
      concentration at equilibrium in solution. Intact MAG, which bears multiple
      antigenic oligosaccharides, and monovalent oligosaccharides generated by pronase
      digestion of MAG were used as antigen. The human antibodies bound to intact MAG
      with dissociation constants of between 2.5 x 10(-10) M and 2.1 x 10(-7) M, and to
      the monovalent oligosaccharides with up to 100-fold lower affinities. Reduction
      of the pentameric IgM to its monomeric counterpart reduced its affinity to intact
      MAG 5-fold, but its avidity for immobilized MAG was reduced 500-fold as
      determined by ELISA. These studies show that IgM Anti-MAG antibodies exhibit
      relatively low intrinsic affinities for the oligosaccharide antigen, but their
      affinities and avidities are significantly increased by the multivalent nature of
      the antibody-antigen interaction.

PMID- 7515899
TI  - Human T lymphocytes distinguish bovine from human P2 peripheral myelin protein:
      implications for immunological studies on inflammatory demyelinating
      neuropathies.
AB  - In patients with inflammatory demyelinating neuropathy, which is possibly
      mediated by autoreactive, myelin-specific T lymphocytes, most studies focusing on
      immune responses to the major neuritogenic myelin protein P2 have been performed
      with bovine P2. However, the primary structure of bovine P2 differs from the
      human protein by nine amino acid residues that may profoundly influence the
      antigen recognition by T lymphocytes. We purified bovine and human P2 from
      peripheral nervous tissue and established a total of 19 T cell lines (TCL)
      reactive with bovine P2 from blood of two patients with acute Guillain-Barre
      syndrome (n = 5 TCL) and from six healthy individuals. Only four of these TCL,
      all raised from the blood of the GBS patients, transiently cross-recognized human
      P2 protein. Our results suggest that the use of human autoantigen may be crucial
      for the characterization of T cellular immune responses against P2 protein both
      in patients with inflammatory demyelinating neuropathy and in healthy controls.

PMID- 7515900
TI  - Monoclonal and polyclonal antibody responses to the myelin basic protein epitope
      present in human urine.
AB  - The myelin basic protein (MBP)-like material (MBPLM) in human urine is expressed
      in a cryptic epitope(s) present in MBP peptide 80-89 and absent or inaccessible
      in intact MBP. These features of urinary MBPLM have made it difficult to produce
      reagents for its further characterization. Using an immunogen of keyhole limpet
      hemocyanin conjugated to MBP peptide cys 74-89, polyclonal antiserum to urinary
      MBPLM was prepared. With the same immunogen and screening with urine, the product
      from one of over 1600 wells from the original fusion, produced monoclonal
      antibody (mAb) which could detect urinary MBPLM. By radioimmunoassay two rabbit
      polyclonal reagents recognized a cryptic epitope in MBP peptide 84-89 while the
      two mAbs recognized another cryptic epitope in MBP peptide 80-85. Both could be
      used for quantitation of MBPLM in urine. These and previous results indicate the
      presence of at least three epitopes, one noncryptic and two cryptic, in the
      decapeptide of MBP 80-89. Of the two cryptic epitopes, the one near the carboxyl
      terminal is dominant to that in the amino-terminal portion. The detection of
      urinary MBPLM with reagents with two different specificities suggests the
      presence of two or more small MBP peptides in urine.

PMID- 7515901
TI  - Eosinophils within the healthy or inflamed human intestine produce substance P
      and vasoactive intestinal peptide.
AB  - The purpose of this study was to show if inflammatory cells within healthy or
      diseased human intestinal mucosa produce some regulatory neuropeptides. First,
      inflammatory cells were isolated from the intestinal lamina propria of 11
      patients with ulcerative colitis or Crohn's disease. Also collected were cells
      from anatomically normal intestine derived from five patients requiring bowel
      resection for diseases not related to inflammatory bowel disease. Extracts of
      these isolated cells contained authentic substance P (SP) and vasoactive
      intestinal peptide (VIP) as shown by RIA and their elution profiles on HPLC.
      Immunostaining of cells from nine of 13 additional patients localized
      immunoreactive SP and VIP to secretory granules within most mucosal eosinophils.
      No other cell types stained positive. Messenger RNA encoding SP and VIP was
      localized to lamina propria eosinophils by in situ hybridization. Mucosa
      inflammatory cells, from eight of nine more patients, cultured in vitro, released
      detectable amounts of VIP, but not SP. It is concluded that intestinal
      eosinophils produce SP and VIP. Since the eosinophils store and release more VIP
      than SP, it is possible that VIP is the preferred secretory product.

PMID- 7515902
TI  - Regulation of immunoglobulin production by nerve growth factor: comparison with
      anti-CD40.
AB  - Nerve growth factor (NGF) is a well-known neurotrophic factor acting on both the
      peripheral and the central nervous systems. In addition, it has been shown to
      play a role in the function of the immune system through specific receptors. The
      low-affinity NGF receptor (NGFR) is present on human B lymphocytes and has been
      shown to have structural homology with another specific B cell surface molecule,
      CD40. NGF and anti-CD40 have been shown to modulate B-cell proliferation and
      Immunoglobulin (Ig) secretion. However, there have been no studies directly
      comparing the properties of these putative B-cell growth factors, particularly
      similarities in receptor expression or their role in B cell function. In this
      study, we examined the expression of NGFR and CD40 in a number of B
      lymphoblastoid cell lines, representative of various stages of differentiation.
      We found that NGFR and CD40 are expressed on all B-cell lines to various degrees
      with the exception of plasma cells. Using two Ig secreting cell lines, both NGF
      and anti-CD40 decreased Ig secretion in a dose-dependent manner. The interaction
      of NGF and anti-CD40 with interleukin-4 (IL-4) was surprisingly different.
      Whereas IL-4 reversed the inhibitory effect of NGF on Ig secretion, it did not
      reverse that of anti-CD40. In addition, differences were observed at the level of
      receptor expression; IL-4 decreased the expression of NGFR, but increased that of
      CD40. These data indicate that although NGFR and CD40 are expressed in a co
      ordinate fashion on B cells and exert similar effects on Ig secretion,
      differences in interaction with other growth factors may be important in their
      activities at different stages of B-cell differentiation.

PMID- 7515903
TI  - Myelin basic protein gene polymorphism is not associated with chronic progressive
      multiple sclerosis.
AB  - In the present study a tetranucleotide (TGGA)n repeat polymorphism 5' to the
      myelin basic protein (MBP) gene was evaluated in a group of HLA-class II-typed,
      chronic progressive multiple sclerosis (MS) patients. This polymorphism has been
      reported by others to be associated with MS. Contrary to these reports we
      observed similar allele frequencies in patients and controls. Our results
      indicate that there is no association between MS and a polymorphism 5' to the MBP
      gene.

PMID- 7515904
TI  - NADPH diaphorase (nitric oxide synthase)-containing nerves in the
      enteropancreatic innervation: sources, co-stored neuropeptides, and pancreatic
      function.
AB  - Pancreatic ganglia are innervated by neurons in the gut and are formed by
      precursor cells that migrate into the pancreas from the bowel. The innervation of
      the pancreas, therefore, may be considered an extension of the enteric nervous
      system. NADPH-diaphorase is present in a subset of enteric neurons. We
      investigated the presence of NADPH-diaphorase in the enteropancreatic
      innervation, the contribution of extrinsic nerves to the NADPH-diaphorase
      containing fibers of the gut and pancreas, and the coincident expression of NADPH
      diaphorase NADPH-diaphorase in intrinsic neurons of these organs with
      neuropeptides. The possible role of nitric oxide in the neural regulation of
      pancreatic secretion was studied in isolated pancreatic lobules. Neuronal
      perikarya with NADPH-diaphorase activity were found in both Dogiel type I and
      type II neurons of the myenteric plexus of the stomach and duodenum. All galanin
      (GAL)-immunoreactive neurons and a small subset of vasoactive intestinal
      polypeptide (VIP)- and neuropeptide Y (NPY)-immunoreactive neurons contained
      NADPH-diaphorase activity. NADPH-diaphorase activity was also found in a subset
      of VIP and NPY-immunoreactive pancreatic neurons. Retrograde tracing with
      FluoroGold established that NADPH-diaphorase-containing neurons in the bowel
      project to the pancreas. NADPH-diaphorase-containing fibers were also found to be
      provided to both organs by neurons in dorsal root ganglia. Secretion of amylase
      was evoked by L-arginine. This effect was prevented by N(G)-nitro-L-arginine (L
      NNA), which also inhibited VIP-stimulated secretion of amylase; however, L-NNA
      had no effect on amylase secretion stimulated by carbachol. These results provide
      support for the hypothesis that nitric oxide plays a role in the neural
      regulation of pancreatic secretion.

PMID- 7515905
TI  - Primary olfactory fibres project to the ventral telencephalon and preoptic region
      in trout (Salmo trutta): a developmental immunocytochemical study.
AB  - We studied the development of the primary olfactory system of a teleost, the
      brown trout, with the aims of clarifying whether the caudal projection pertains
      to the olfactory or to the terminal nerve system, of identifying the brain
      regions receiving this projection, and of investigating its possible functional
      significance. As olfactory markers (OMs) we used two polyclonal antibodies (to
      substance P and to alpha-melanocyte-stimulating hormone) that were found to label
      the olfactory projection strongly after preadsortion of the antibody with the
      corresponding antigen (OMs), and as a terminal nerve marker we used an antiserum
      to FMRF-amide peptide. OM labelling was observed in both perikarya and axons of
      olfactory neurons. In adults, olfactory neurons projected not only to olfactory
      glomeruli in the olfactory bulb but also, as has been reported previously, to
      more caudal targets in the forebrain through the medial olfactory tract. Our
      results show that these targets include the ventral and commissural nuclei of the
      area ventralis telencephali, the periventricular preoptic region, and the organum
      vasculosum laminae terminalis. Glomeruli were not observed before hatching, and
      the extrabulbar olfactory projections appear late in development. Extensive
      periventricular preoptic olfactory plexuses and olfactory innervation of the
      organum vasculosum laminae terminalis did not appear until adulthood. The cells
      of the ganglion nervus terminalis, which form ganglionic groups along the
      olfactory nerves, were not stained with these olfactory markers at any
      developmental stage studied, nor was the medial olfactory tract FMRP-amide
      peptide immunoreactive. Our results thus confirm the existence of primary
      olfactory projections to extrabulbar targets in trout. The target regions
      identified in this study are implicated in sexual behaviour: We discuss the
      related possibility that, in teleosts, these extrabulbar olfactory projections
      (rather than projections of the terminal nerve, as is widely held) are the
      primary mediators of neuroendocrine response to pheromones.

PMID- 7515906
TI  - 5-HT innervation of reticulospinal neurons and other brainstem structures in
      lamprey.
AB  - In order to determine if reticulospinal neurons involved in the control of
      locomotion and responsive to exogenously applied 5-hydroxytryptamine (5-HT) are
      innervated by fibers that contain serotonin, the serotoninergic innervation of
      reticulospinal neurons, identified by retrograde labeling with fluorescein
      conjugated dextran-amine (FDA), was investigated by immunohistochemistry in the
      lamprey brainstem. A widespread distribution of 5-HT immunoreactive (5-HT-ir)
      fibers was seen within the basal plate of the brainstem, an area containing
      reticulospinal somata and dendritic aborizations. Numerous 5-HT varicose fibers
      were found in close relation to large reticulospinal cell bodies, particularly in
      the middle and anterior rhombencephalic reticular nuclei (MRRN and ARRN). Some of
      these reticulospinal somata were surrounded by a very dense pericellular 5-HT
      innervation. 5-HT-ir fibers were also seen in other brain structures that are
      known to influence reticulospinal neurons such as the rhombencephalic alar plate
      containing sensory relay interneurons, cranial nerves (III-X), cerebellum, and
      tectum. These findings suggest that, as in the spinal cord, motor behavior
      controlled by reticulospinal neurons may be subject to a serotoninergic
      modulation.

PMID- 7515907
TI  - Further characterization of the effects of brain-derived neurotrophic factor and
      ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor
      neurons.
AB  - Neurotrophins and neural cytokines are two broad classes of neurotrophic factors.
      It has been reported that ciliary neurotrophic factor (CNTF) and brain-derived
      neurotrophic factor (BDNF) prevent the degeneration of axotomized neonatal motor
      neurons. In addition, BDNF is transported retrogradely to alpha-motor neurons
      following injection into the muscle, and patterns of BDNF expressed in spinal
      cord and muscle suggest a physiological role for this factor in motor neurons. In
      the present study, we characterize the effects of BDNF on axotomized neonatal
      facial motor neurons and extend these observations to adult models of motor
      neuron injury (axotomy-induced phenotypic injury of lumbar motor neurons). BDNF
      reduces axotomy-induced degeneration of neonatal neurons by 55% as determined by
      Nissl staining (percentage of surviving neurons in vehicle-treated cases, 25%; in
      BDNF-treated cases, 80%). Rescued neurons have an intact organelle structure but
      appear smaller and slightly chromatolytic on electron microscopic analysis. As
      demonstrated by intense retrograde labeling with horseradish peroxidase (HRP)
      applied to the proximal stump of the facial nerve, neurons rescued by BDNF have
      intact mechanisms of fast axonal transport. CNTF did not appear to have
      significant effects on neonatal motor neurons, but the lack of efficacy of this
      factor may be caused by its rapid degradation at the application site. BDNF is
      not capable of reversing the axotomy-induced reduction in transmitter markers
      [i.e., the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT) or
      the degrading enzyme acetylcholinesterase (AChE) in neonatal or adult animals or
      the axotomy-induced up-regulation of the low-affinity neurotrophin receptor
      p75NGFR (nerve growth factor receptor) in adult motor neurons. However, BDNF
      appears to promote the expression of p75NGFR in injured neonatal motor neurons.
      In concert, the findings of the present study suggest that BDNF can significantly
      prevent cell death in injured motor neurons. However, this neurotrophin may not
      be a retrograde signal associated with the induction and/or maintenance of some
      mature features of motor neurons, particularly their transmitter phenotype.

PMID- 7515908
TI  - Cytotoxic T cell repertoire selection. A single amino acid determines alternative
      class I restriction.
AB  - CTL responses are governed by intracellular Ag processing, affinity of peptides
      for MHC class I molecules, and the T cell repertoire. In this report we
      demonstrate that a class I Dd-restricted 10-mer CTL epitope within the gp160
      envelope glycoprotein of HIV-1 strain IIIB (residues 318-327) contains a 9-amino
      acid peptide (residues 319-327), which efficiently binds to both the Dd and Ld
      class I molecules in vitro. The potential for broadening the naturally limited
      CTL response to include presentation on the Ld class I molecules in vivo was
      examined using a minigene-based vaccine strategy to insure cytosolic expression
      of "preprocessed" forms of the gp160 epitope. Immunization with recombinant
      vaccinia viruses (vac) expressing either the gp160 10 mer or 9 mer, both
      including an initiation methionine (M318-327 and M319-327, respectively), induced
      predominantly Dd-restricted CTL specific for native gp160. By contrast,
      recombinant vac expressing eight gp160 amino acids (M320-327) generated
      predominantly Ld-restricted CTL which are specific for synthetic gp160 peptides
      but not native gp160. The ability to induce Ld-restricted CTL suggests that the
      absence of an Ld-restricted response to native gp160 cannot be attributed to a
      limited T cell repertoire, but to inefficient processing of gp160 for
      presentation on Ld. The switch in class I restriction, controlled by a single
      amino acid within one epitope, demonstrates that nonanchor residues have a
      profound effect on differential MHC restriction and CTL induction. Thus, minigene
      based vaccines expressing minimal epitopes may be useful in inducing a more
      heterogeneous CTL response than previously appreciated.

PMID- 7515909
TI  - Activation induces sensitivity toward APO-1 (CD95)-mediated apoptosis in human B
      cells.
AB  - We have previously described the APO-1 (CD95) cell surface molecule, a novel
      member of the nerve growth factor/TNF receptor superfamily, identical with the
      Fas Ag. Triggering of APO-1-induced apoptosis in APO-1+, apoptosis sensitive
      cells. The data in this study demonstrate that human peripheral blood B cells
      acquire sensitivity to APO-1-mediated apoptosis on PWM activation. To also study
      APO-1-mediated apoptosis in an Ag-specific human B cell response, we
      reconstituted severe combined immunodeficient (SCID) mice i.p. with human PBMC
      (SCID-hu mice). SCID-hu mice were then injected i.p. with soluble, adjuvant-free
      tetanus toxoid or diphtheria toxoid, respectively, directly after transfer of the
      PBMC (day 1) and received an Ag-booster injection on day 14. Two weeks after PBMC
      transfer human Abs were detected and shown to be Ag specific. SCID-hu mice co
      injected with monoclonal anti-APO-1 Ab (IgG3,k) showed significantly suppressed
      anti-tetanus toxoid or anti-diphtheria toxoid titers, respectively. Sensitivity
      to anti-APO-1-mediated suppression was only observed in Ag-activated cells from
      day 0 to day 6 after Ag immunization. Suppression of Ab titers correlated with a
      decrease of Ag-specific Ig-secreting cells. Re-injection of syngeneic T cells and
      Ag did not reverse anti-APO-1-induced suppression. These data show a direct
      suppressive effect of anti-APO-1 on Ag-activated, "specific" B cells. Thus, APO-1
      mediated apoptosis in Ag-activated B cells may contribute to the regulation of
      the humoral immune response.

PMID- 7515910
TI  - Costimulation through CD28 enhances T cell-dependent B cell activation via CD40
      CD40L interaction.
AB  - Changes in T cell helper function were analyzed when anti-CD3-activated T cells
      were costimulated with mAbs to the CD28 receptor (anti-CD28). T cell-dependent B
      cell growth and differentiation were consistently augmented if anti-CD3
      stimulated-T cells were simultaneously activated with anti-CD28. Although anti
      CD28 enhanced IL-2 and IL-4 production, it did not increase B cell responses
      solely by augmenting production of soluble lymphokines. Anti-CD28 costimulation
      induced increases on T cells of CD40 ligand (CD40L), known to promote B cell
      proliferation and Ig secretion. Because anti-CD28 promoted T cell helper
      functions and expression of CD40L, we examined the dependence for CD40L during T
      cell-dependent B cell responses. Although soluble CD40 fusion proteins only
      partially inhibited T cell-dependent B cell activation, we found a strict
      requirement for CD40L expression at initiating B cell responses. Both CD40L
      expression and T cell help were blocked by cyclosporin A after TCR cross-linking,
      and, unlike T cell proliferation, both remained cyclosporin A sensitive during
      CD28 costimulation. In addition, anti-CD28 could not compensate for the T cell
      helper deficiency of hyper IgM syndrome patients who lack functional CD40L. Thus,
      anti-CD28-induced T cell help is delivered via a CD40L-dependent process. The
      fact that cross-linking CD40 on B cells promotes expression of the B7/BB-1 ligand
      for CD28 suggest T and B interactions may have a reciprocal amplification
      mechanism.

PMID- 7515911
TI  - Molecular context of a viral T cell determinant within a chimeric bacterial
      protein alters the diversity of its T cell recognition.
AB  - We genetically introduced two different viral CD4+ T cell epitopes within two
      internal sites of the Escherichia coli maltose-binding (MalE) protein. Affinity
      purified hybrid MalE proteins were used to analyze the influence of the molecular
      environment on the presentation of inserted epitope to T cells. In the first
      model, the 120 to 132 PreS T cell epitope was inserted alone or with its C
      terminal B cell epitope (132-145) at site 133 or 303 of MalE. The maltose-binding
      protein with PreS peptide inserts expressing the 120 to 132 sequence were able to
      induce in vivo and in vitro peptide-specific T cell response, whatever the length
      and the position of the insert. In the second model, the 103 to 115 T cell
      epitope from the C3 region of poliovirus type 1 (PV1) was inserted, with various
      flanking sequences, either at site 133 or 303 of MalE protein. The longer C3:86
      to 115 insert induced poliovirus-specific T cell responses at both sites of MalE,
      whereas the C3:93 to 115 insert did it only at site 303 but not at site 133.
      Moreover, C3:103 to 115 specific T cell hybridomas discriminated between the
      processed peptides generated from the different chimeric proteins, as a result of
      differences in the length and the position of the inserted sequence. Therefore,
      in this experimental model the loss of in vivo immunogenicity of an antigenic
      determinant within a chimeric protein is related to the activation of a reduced T
      cell repertoire. These observations involve important consequences for the
      engineering of recombinant vaccines.

PMID- 7515912
TI  - IL-4 treatment of small splenic B cells induces costimulatory molecules B7-1 and
      B7-2.
AB  - IL-4 has been shown to be involved in the early stages of B cell maturation.
      Changes induced by IL-4 include cell enlargement, increased viability, and
      increased MHC class II expression. However IL-4 alone does not induce B cell
      activation as defined by proliferation, lymphokine production, or Ig class
      switching. In this study, we demonstrate that incubation with IL-4 enhances the
      ability of small splenic murine B cells, normally poor stimulators of murine Th1
      clones, to stimulate lymphokine production and proliferation by Th1 clones.
      Moreover, small resting B cells induce anergy, whereas IL-4-treated B cells do
      not. IL-4-treated B cells were found to express both B7 (B7-1) and a second
      ligand for CTLA4Ig (B7-2). Although IL-4 induces both B7-1 and B7-2, the kinetics
      of expression of these molecules are different: B7-2 is detected by 6 h, whereas
      B7-1 is not detectable until 48 h. In addition, only CTLA4Ig fully blocks IL-4
      induced costimulatory activity; a mAb to B7-1 does not. Thus, these results
      suggest that IL-4 may function indirectly as a costimulatory factor by inducing
      costimulatory molecules on resting B cells. Additionally, these findings support
      our previous findings that an alternative ligand for CD28 and CTLA4 is important
      in providing costimulation.

PMID- 7515913
TI  - CD23 interacts with a new functional extracytoplasmic domain involving N-linked
      oligosaccharides on CD21.
AB  - Human CD21 has been described as a receptor for the C3d,g and iC3b proteins of
      complement, for the Epstein-Barr virus, and also for IFN-alpha. We reported
      recently that CD23, a low affinity receptor for IgE (Fc epsilon R2), is a new
      functional ligand for CD21. To determine the site of interaction of CD23 on CD21,
      we analyzed the ability of purified recombinant CD23 incorporated into
      fluorescent liposomes to bind CD21 mutants bearing various deletions of
      extracytoplasmic short consensus repeats (SCRs). We found that the site of
      interaction of CD23 on CD21 is on SCRs 5 to 8, with contribution of SCRs 1 and 2.
      Tunicamycin treatment of CD21-transfected K562 cells strongly inhibited the
      binding of CD23-liposomes, suggesting that an N-linked sugar, present on SCRs 5
      to 8, is involved in the CD23/CD21 interaction. By mutating together or
      individually, the three asparagines present on SCRs 5 to 8, asparagines (Asn) 370
      and 295, but not Asn 492, were shown to be involved critically in the binding of
      CD23. Furthermore, we mapped the binding sites of a panel of anti-CD21 mAbs and
      found that at least six epitopes can be detected on CD21. The mAbs that inhibit
      the most CD23 binding to CD21 map in SCRs 5 to 8. This study indicates that SCRs
      5 to 8 represent a novel functional domain on the CD21 molecule, and is the first
      demonstration of an activity of an extracytoplasmic region of the CD21 outside of
      SCRs 1 to 4.

PMID- 7515914
TI  - In vivo and in vitro functional examination of a conserved epitope of L- and E
      selectin crucial for leukocyte-endothelial cell interactions.
AB  - Selectins constitute a three-member gene family of carbohydrate-binding adhesion
      proteins found on the surface of leukocytes and endothelial cells that is central
      to inflammation-associated leukocyte recruitment and lymphocyte recirculation. E-
      and P-selectin are inducible and expressed on the surface of endothelial cells
      under inflammatory conditions, whereas L-selectin is constitutively expressed on
      most circulating leukocytes. Previously, we have characterized a unique mAb (EL
      246) that recognizes a common epitope on both E- and L-selectin, which is
      presented or determined by their short consensus repeat domains. This report
      defines the functional properties of EL-246 and its cognate epitope. In a novel
      in vitro physiologic shear system, we show that neutrophil rolling on activated
      HUVECs and on E-selectin cDNA transfectants is blocked 45 to 120 s after infusion
      of EL-246. The examination of the binding of neutrophils to E-selectin cDNA
      transfectants reveals that their adhesion is blocked by EL-246 treatment of
      either cell type. A unique Ab transfer mechanism is demonstrated in which El-246
      is delivered unidirectionally from L- to E-selectin to surpass the adhesion
      blocked by mAbs that recognize either L- or E-selectin alone. By using flow
      cytometry and in vivo homing techniques, we show that pretreating bovine
      lymphocytes with EL-246 blocks their ability to home to mouse peripheral lymph
      nodes by > 65%. Cumulatively, these results suggest that EL-246 is a uniquely
      potent pharmacologic inhibitor of leukocyte-endothelial cell interactions that
      are mediated by either E- or L-selectin.

PMID- 7515915
TI  - Monoclonal antibody to an activation neoepitope of alpha M beta 2 inhibits
      multiple alpha M beta 2 functions.
AB  - alpha M beta 2, a beta 2 integrin expressed on cells of myelomonocytic
      differentiation, functions as a receptor for factor X (X) and fibrinogen (Fg) and
      participates in leukocyte adhesion to vascular endothelium. Acquisition of high
      affinity ligand binding has been suggested to result from a conformational change
      of alpha M beta 2 in response to agonist-induced leukocyte stimulation. We now
      describe mAb 7A10, which preferentially binds to alpha M beta 2 on activated
      cells and reports the functional activation of this integrin. Agonist-stimulated
      monocytes and monocytic cells, but not resting cells, maximally expressed the
      7A10 neoepitope, whereas expression of other selected alpha M beta 2 epitopes
      remained unchanged. The neoepitope was elicited equally by exposure of cells to
      either ADP or FMLP and did not require divalent cations for expression.
      Saturation of the 7A10 neoepitope by this Ab on stimulated THP-1 cells inhibited
      both X and Fg binding and abolished the alpha M beta 2-driven cellular coagulant
      response. Stimulated monocytic cells, which bound X and/or Fg, exhibited a
      sustained adhesion to unstimulated endothelial cell monolayers and Ab 7A10
      inhibited this sustained adhesion. We conclude that activated conformers of alpha
      M beta 2 mediate X and Fg binding, that assembly of either X or Fg or both on
      alpha M beta 2 mediates leukocyte adhesion to unstimulated endothelium through
      sparse ICAM-1, and that mAb 7A10 can report and functionally inhibit this pathway
      of leukocyte adhesion.

PMID- 7515916
TI  - Transforming growth factor-beta 1 mediates mast cell chemotaxis.
AB  - It remains unknown which factor(s) control mast cell recruitment in chronic
      immune reactions. Although TGF-beta has been shown to function as a potent
      chemotactic factor for monocytes, fibroblasts, and neutrophils, its effect on
      mast cells has not been previously determined. In this study, TGF-beta 1 was
      shown to cause directed migration of cultured mouse mast cells at femtomolar
      concentrations, with a maximal chemotactic response observed at 25 fM. Moreover,
      chemotaxis to TGF-beta was also seen using freshly isolated rat peritoneal mast
      cells. Addition of neutralizing Ab to TGF-beta abrogated its chemotactic activity
      for both freshly isolated rat peritoneal mast cells and cultured mouse mast
      cells, whereas an irrelevant species-matched control Ab had no effect.
      Checkerboard analysis confirmed the mast cell chemotactic activity after exposure
      to concentration gradients of TGF-beta. Mast cells were observed to undergo rapid
      and extensive shape changes on exposure to TGF-beta, assuming a polarized
      morphology in preparation for migration. Other known mast cell chemoattractants
      including laminin, c-kit ligand, and IL-3 were found to be considerably less
      potent on a molar basis in inducing directed migration. Affinity cross-linking
      studies identified TGF-beta binding proteins with M(r) at 70 and 288 kDa,
      consistent with types I and III TGF-beta receptors on the mast cells. In summary,
      TGF-beta is the most potent chemoattractant described for mast cells and
      conceivably relevant, because pathologic processes mediated by TGF-beta are often
      associated with mast cell accumulation.

PMID- 7515918
TI  - CD31 (PECAM-1), CDw32 (Fc gamma RII), and anti-HLA class I monoclonal antibodies
      recognize phosphotyrosine-containing proteins on the surface of human
      neutrophils.
AB  - Although most studies of protein phosphorylation have focused on intracellular
      reactions, studies have provided evidence for the existence of ectoprotein kinase
      activity on the surface of some cells including human neutrophils. The
      identification and characterization of physiologic substrates of ectoprotein
      kinase activity should aid the understanding of the role of this enzyme activity
      in cell function. Immunoprecipitation and subsequent gel electrophoresis of
      proteins from neutrophils labeled with [gamma-32P]ATP under conditions initially
      designed to detect ectoprotein kinase activity revealed that CD31, CDw32, and
      anti-HLA class I mAbs specifically recognize phosphoproteins on the surface of
      human neutrophils. Phosphorylation of these proteins was inhibited by
      pretreatment of cells with an impermeant sulfhydryl reagent before radiolabeling.
      Phosphoamino acid analysis of the proteins revealed that they contained
      predominantly phosphotyrosine. However, controlled proteolysis of intact cells
      and purified HLA class I revealed that the HLA class I heavy chain was
      phosphorylated on the cytoplasmic domain. These results suggest that the
      molecules recognized by CD31 (PECAM-1) and CDw32 (Fc gamma RII) Abs may also be
      phosphorylated on cytoplasmic domains under conditions originally designed to
      detect ectoprotein kinase activity. Phosphorylation of CD31 (PECAM-1), Fc gamma
      RII, and HLA class I heavy chain on tyrosine may play a role in regulating their
      function. These results emphasize that the demonstration that a membrane protein
      is an ectokinase substrate is complex and requires the definitive localization of
      the phosphorylated residue to the extracellular domain of the protein.

PMID- 7515917
TI  - Recombinant soluble CD14 inhibits LPS-induced tumor necrosis factor-alpha
      production by cells in whole blood.
AB  - CD14 functions as a cell surface receptor for LPS in the activation of
      monocytes/macrophages and neutrophils by endotoxin. To assess the utility of
      soluble forms of the CD14 receptor as a possible therapeutic for endotoxin shock,
      we have produced recombinant human soluble CD14 using a baculovirus expression
      system. We find that the recombinant protein is not only expressed on the surface
      of the insect cells as a glycosyl phosphatidylinositol (GPI)-anchored protein,
      but is also released into the culture medium as a soluble form that lacks the GPI
      anchor. Functional analyses of recombinant human soluble CD14 show that it binds
      specifically to LPS and can inhibit the LPS-induced release of TNF-alpha by
      macrophages and mononuclear cells as well as by cells in whole human blood when
      used at concentrations of approximately 70 micrograms/ml. Thus, soluble CD14 may
      be useful as an adjunct in the treatment of endotoxin shock.

PMID- 7515919
TI  - B cell differentiation defects in common variable immunodeficiency are
      ameliorated after stimulation with anti-CD40 antibody and IL-10.
AB  - In these studies we show that although purified B cells of patients with common
      variable immunodeficiency (CVI) have a normal capacity to proliferate, they
      manifest differentiation defects at multiple levels. Compared with controls,
      circulating CVI B cell populations contain reduced numbers of sIgG+ and sIgA+
      cells with a commensurate increase in sIgM+ B cells, suggesting an in vivo defect
      in isotype switch. In addition, CVI B cells manifest Ig secretion defects on
      stimulation with either anti-CD40 and IL-10 or SAC and IL-2 and IL-10, which are
      of increasing severity for IgM, IgG, and IgA, respectively. These Ig secretion
      defects are not overcome by addition of a variety of cytokines, including TGF
      beta, to anti-CD40-driven cultures. In further studies we show that despite the
      above abnormalities, CVI B cells are induced to express normal or near-normal
      levels of C mu, C gamma, and C alpha mRNA after 7 days of stimulation with anti
      CD40 and IL-10. That this CH mRNA expression represents a recovery of CVI B cell
      differentiation is supported by studies of Ig secretion in which CVI B cells that
      are first stimulated for 7 days with anti-CD40 and IL-10 and then restimulated in
      coculture with activated normal allogeneic T cells and IL-10, secrete substantial
      levels of IgM and IgG and increased amounts of IgA. Overall, therefore, CVI B
      cell function can be significantly improved by maintenance in culture. These data
      suggest the abnormalities of B cell differentiation in CVI are reversible and
      that the defect is a form of B cell anergy.

PMID- 7515920
TI  - CD58 (LFA-3) stimulation provides a signal for human isotype switching and IgE
      production distinct from CD40.
AB  - Induction of an IgE response involves several discrete steps: 1) induction of
      epsilon germ line transcription, 2) DNA recombination, and 3) mature RNA
      transcription/translation. Here we show that ligation of B cell CD58 by CD2, its
      natural ligand on T cells, or by mAb, provides a novel IL-4-dependent signal for
      the latter two steps. Highly purified human B cells were induced to produce IgE
      by costimulation with IL-4 and CD58 mAb. Although CD58 ligation alone was unable
      to induce epsilon germ-line transcription, in concert with IL-4-stimulated
      epsilon germ-line transcription it induced the appearance of productive epsilon
      transcripts and IgE production. The direct involvement of CD2 was demonstrated: B
      cells cultured with IL-4 plus murine T hybridoma cells transfected with human CD2
      produced IgE. A CD40 Fc fusion protein had no effect on CD58-driven IgE
      production while inhibiting CD40-dependent responses. Furthermore, cells from
      patients with common variable immunodeficiency produced IgE in response to IL-4
      plus CD40 mAb but not to IL-4 plus CD58 mAb. CD58-driven IgE synthesis was IFN
      gamma independent and was not enhanced by exogenous IL-6. Functional differences
      between CD40 and CD58 IgE stimulation were demonstrated. Thus, the CD2:CD58
      ligand/counterligand system provides an alternative pathway by which cell contact
      signaling may regulate IgE. Given the relative importance of CD2 triggering on
      mucosal T cells and the mucosal location of IgE production, this may be
      especially true on mucosal surfaces.

PMID- 7515921
TI  - Human T cell-dependent B cell differentiation induced by staphylococcal
      superantigens.
AB  - Microbial superantigens (SAgs), by virtue of their binding to TCR V beta elements
      on T cells and to class II MHC molecules on accessory cells (AC), trigger T cell
      activation. Although anti-CD3 mAb (which also trigger T cell activation via
      surface CD3/TCR) can readily induce T cell-dependent B cell differentiation in
      unmanipulated PBMC cultures, induction of Ig production in SAg-stimulated
      cultures has usually required special manipulation of the T cells, such as
      irradiating them or treating them with mitomycin C. We now demonstrate that eight
      different staphylococcal SAgs, typically at concentrations 10- to 100-fold lower
      than those required for proliferation, can each trigger unmanipulated peripheral
      blood and tonsil T cells to drive polyclonal B cell differentiation. Such SAg
      induced T cell-dependent generation of Ig-secreting cells (IgSC) requires T cells
      and B cells only and occurs in the absence of monocytes as long as there are
      adequate numbers of B cells to serve as (DR+) AC. Physical contact among T cells,
      responder B cells, and AC (when different from the responder B cells) is
      required. The fusion protein CTLA4Ig inhibits SAg-induced IgSC generation in a
      dose-dependent fashion, whereas a control fusion protein has no such effect. In
      contrast, CTLA4Ig has, at best, only modest effects on SAg-induced T cell
      proliferation, indicating that CD28 (CTLA4)/B7 (B7-like) interactions play a more
      prominent role in SAg-induced IgSC generation than in SAg-induced T cell
      proliferation. These results establish SAg-induced T cell-dependent B cell
      differentiation as a useful model for T cell/B cell interactions, inasmuch as no
      other cell types are necessary for successful B cell differentiation; these
      results also demonstrate the importance of CD28 (CTLA4)/B7 (B7-like)-dependent
      mechanisms in this process.

PMID- 7515922
TI  - Plasmodium falciparum liver stage antigen-1 is well conserved and contains potent
      B and T cell determinants.
AB  - We have previously identified a Plasmodium falciparum liver stage-specific Ag
      (LSA-1) found to encode tandem 17 amino acid repeats harboring B cell
      determinants. Here we extend this study in terms of sequence analysis, protein
      localization, and immunologic properties. Analysis of the N- and C-terminal
      regions of LSA-1 from the T9/96 clone reveals high sequence conservation with LSA
      1 from NF54. This 200-kDa protein is detected throughout liver schizogony and
      accumulates in the parasitophorous vacuole space. In our investigation of T and B
      cell responses to LSA-1, we have focused on both the area of the C-terminal,
      nonrepetitive "hinge" region and the conserved repetitive region and derived
      synthetic peptides. These were found to contain major B and T cell determinants.
      High prevalences and elevated Ab levels to LSA-1, directed primarily, although
      not exclusively, to the repetitive region, were detected in sera of individuals
      from one moderately high and two low transmission malaria-endemic areas
      (prevalences of 97%, 75, and 77%, respectively). In one of these low transmission
      areas, secretion of the cytokine IFN-gamma, known to inhibit malaria liver
      stages, and T cell proliferation were detected in PBMC of 22 to 48% and 6 to 20%,
      respectively, of individuals in response to separate LSA-1 peptides. These
      results complement the recent finding of conserved CTL epitopes in LSA-1 and
      support the assertion that immune responses to LS Ag are involved in protection
      against malaria pre-erythrocytic stages.

PMID- 7515924
TI  - Discordant adaptation of human peritoneal macrophages to stimulation by
      lipopolysaccharide and the synthetic lipid A analogue SDZ MRL 953. Down
      regulation of TNF-alpha and IL-6 is paralleled by an up-regulation of IL-1 beta
      and granulocyte colony-stimulating factor expression.
AB  - Human peritoneal macrophages were exposed to increasing doses of LPS or a
      synthetic lipid A analogue (SDZ MRL 953) and production of the cytokines IL-1
      beta, IL-6, TNF-alpha, and G-CSF was assessed at the protein and mRNA level.
      Cells were also prestimulated with low doses of LPS and SDZ MRL 953 to study
      their adaptation to a secondary challenge with high doses of LPS. The ability of
      macrophages to produce high levels of TNF-alpha and IL-6 after stimulation with
      LPS could be relieved almost completely by preincubating cells with low doses of
      LPS. Decreases of TNF-alpha and IL-6 production resulted from inhibition of gene
      transcription and/or changes in mRNA stability, as transcript levels of these
      cytokines were down-modulated by the process of LPS adaptation. Surprisingly,
      however, adapted cells were able to synthesize even larger quantities of G-CSF
      and IL-1 beta when exposed to a secondary LPS challenge. mRNA levels of the
      adapted cells remained unaltered for IL-1 beta, but were slightly increased for G
      CSF as assessed by Northern blot analysis. High doses of the synthetic lipid A
      analogue SDZ MRL 953 were also able to adapt macrophages to a secondary LPS
      challenge by down-regulating TNF-alpha and IL-6 production, whereas priming
      secretion of G-CSF and IL-1 beta as well. We describe here the discordant
      adaptation of human peritoneal macrophages to a secondary LPS stimulus in vitro.
      These findings appear to have ramifications for the in vivo endotoxin response
      during inflammation and also Gram-negative septicemia.

PMID- 7515923
TI  - Hyaluronate is costimulatory for human T cell effector functions and binds to
      CD44 on activated T cells.
AB  - Lymphohematopoiesis, cell matrix adhesion, homing of leukocytes, T cell
      activation, and tumor metastasis are mediated through the CD44 family of cell
      surface receptors. We have recently shown that anti-CD44 mAb trigger protein
      tyrosine kinase-dependent activation of T cell effector functions. Here, we show
      that hyaluronate (HA), a CD44 ligand, in conjunction with CD3/TCR-mediated
      stimuli, is costimulatory for human peripheral blood T cell proliferation, for IL
      2 production by Th clones, and for release of trypsin-like esterase by cytolytic
      T cell clones. A human T cell line, HUT-78, was found to bind HA and on HA
      coating it was used as a target for cytolytic T cell clones. After anti-CD3
      stimulation, CD3+/CD8+ clones acquire the ability of lysing HA-coated HUT-78
      cells more efficiently than the same HA-uncoated targets. Resting peripheral
      blood T cells and T cell clones do not adhere to HA-coated plates. However, 24-h
      anti-CD3 mAb stimulation gives them the transient ability to bind HA. HA adhesion
      of activated T cells and T cell clones, as well as that of T cell lines, is
      blocked by one anti-CD44 mAb (J-173). Two other anti-CD44 mAbs induce a 10-fold
      increase in HA adhesiveness of anti-CD3-stimulated peripheral blood T cells. This
      impressive HA adhesiveness is also readily blocked by J-173 anti-CD44 mAb. These
      data indicate that 1) HA is costimulatory for human T cell effector functions in
      conjunction with CD3/TCR-mediated stimuli, 2) the capacity to bind HA is acquired
      by resting T cells and T cell clones after anti-CD3 stimulation, and 3) HA
      binding occurs via specific interaction with CD44 molecules expressed on
      activated T cells.

PMID- 7515925
TI  - CR2 is the primary acceptor site for C3 during alternative pathway activation of
      complement on human peripheral B lymphocytes.
AB  - Human cells infected with certain viruses acquire the ability to activate the
      alternative pathway (AP) of complement. Complement receptor 2 on EBV-infected
      lymphoblastoid cell lines has been reported to act as the covalent binding site
      for C3b during AP activation. Using flow cytometry, we investigated the ability
      of normal human peripheral blood leukocytes to activate the AP in homologous
      serum. Deposition of C3 fragments was determined as a measurement of complement
      activation on each of the subpopulations of the blood cells. Incubating human
      peripheral blood leukocytes with homologous or autologous serum resulted in C3
      deposition on B cells and, to a lesser extent, on monocytes and polymorphonuclear
      leukocytes. Complement activation in the presence of Mg2+ ions and EGTA revealed
      major involvement of the AP in the case of B cells, and to a lesser extent for
      other leukocyte populations examined. Preincubation of the leukocytes with
      polyclonal anti-complement receptor 2 Ab markedly decreased the C3 fragment
      deposition, as a result of in vitro AP activation, on B cells, indicating that on
      normal human B cells this receptor may be involved in AP activation. Freshly
      isolated, normal human B cells also bear low but significant amounts of C3d,g
      fragments on their membranes, indicating that this AP activation also occurs in
      vivo. AP activation was partially decreased in the presence of autologous
      erythrocytes (RBC) suggesting that complement regulatory proteins on RBC play a
      role in limiting the AP activation in vivo.

PMID- 7515926
TI  - Tyrosine phosphorylation in activated human neutrophils. Comparison of the
      effects of different classes of agonists and identification of the signaling
      pathways involved.
AB  - The tyrosine phosphorylation responses initiated in human neutrophils by soluble
      and particulate agonists were characterized. Chemotactic factors, hematopoietic
      growth factors, and inflammatory microcrystals stimulated in a time- and
      concentration-dependent manner the tyrosine phosphorylation of distinct patterns
      of substrates: pp120, pp85, pp70, and pp60 in the case of chemotactic factors;
      pp155, pp130, pp120, pp85, pp60, and pp40 in the case of granulocyte macrophage
      CSF; and pp130, pp120, pp70, and pp60 in the case of monosodium urate (MSU)
      crystals. Several of the single bands on one-dimensional blots (including pp40,
      pp70, and pp120) could be resolved into multiple spots on two-dimensional gels.
      The responses of several other chemotactic factors resembled those of FMLP.
      Cytokineplasts retained the capacity to respond to FMLP, granulocyte-macrophage
      CSF, or MSU crystals with a stimulation of tyrosine phosphorylation, and
      contained the major substrates detected in intact neutrophils. Several unrelated
      tyrosine kinase inhibitors (herbimycin A, genistein, and erbstatin) strongly
      diminished the tyrosine phosphorylation response to chemotactic factors.
      Pertussis toxin abrogated the tyrosine phosphorylation response to FMLP, whereas
      protein kinase C (Ro 21-8220, chelerithryn) inhibitors were without effect.
      Chelation of intracellular calcium attenuated the tyrosine phosphorylation
      response to FMLP. These results indicate that G proteins play a crucial role in
      the coupling of chemotactic factor receptors to tyrosine phosphorylation and that
      this coupling occurs in parallel to that of phospholipase C. These results also
      underline the complexity of the transduction pathways implicated in the
      initiation of tyrosine phosphorylation.

PMID- 7515927
TI  - Antigen receptor-mediated transmembrane signaling in Wiskott-Aldrich syndrome.
AB  - The X-linked immunodeficiency Wiskott-Aldrich syndrome (WAS) is a condition that
      includes a deficient anti-polysaccharide Ab response. Recently, it has been
      suggested that B cells from patients with WAS show a defective calcium
      mobilization response upon engagement of sIgM. Because primarily EBV-transformed
      cells were used in these studies, we tested freshly isolated blood B cells for
      their calcium mobilization capability upon engagement of sIg and CD19. No
      significant differences in the calcium mobilization capability of CD20+ B cells
      of four individual WAS patients compared with capability in normal controls were
      found. Receptor desensitization as assessed by calcium mobilization inhibition
      also seemed to be intact. T cells were tested for their anti-CD3-induced calcium
      flux and, again, no abnormalities could be observed when compared with T cells
      from healthy individuals. We conclude that WAS B and T cells can be stimulated
      into a normal calcium mobilization response when their AgRs are cross-linked. It
      is highly improbable that the immune dysfunction observed in WAS patients is
      related to a direct disorder of their B and/or T cell AgRs.

PMID- 7515928
TI  - Anergy and apoptosis in CD8+ T cells from HIV-infected persons.
AB  - CD8+T cells from HIV-infected persons increase early in infection, display
      increased levels of activation Ags, and abnormal MHC-restricted, HIV-specific and
      nonspecific cytotoxicity abilities. Paradoxically, these cells are also
      unresponsive to T cell signaling in vitro and have decreased in vitro cloning
      potential. HIV-specific CTL precursors also are lost late in infection. A
      quantitative Southern blotting technique showed that CD8+ T cells from
      asymptomatic, HIV-infected persons have increased DNA fragmentation after
      overnight incubation. DNA fragmentation was reduced by an endonuclease inhibitor
      but not by cycloheximide, suggesting that a pre-apoptotic state exists in vivo.
      Partial inhibition of DNA fragmentation also could be induced by IL-2 addition.
      No consistent difference in fragmentation was observed among CD8+ subpopulations
      from HIV-infected individuals, although only CD8+ T cells that did not express
      activation Ags (DR-, CD28+, CD57- phenotype) showed reduced fragmentation when
      incubated in IL-2. A dramatic increase in CD8+, CD28- cells was observed in
      asymptomatic HIV-infected people. A subset of CD8+, CD28- cells in both controls
      and HIV-infected people do not proliferate to T cell signals, and these cells
      from controls demonstrate increased DNA fragmentation in vitro after 3 days of
      incubation, regardless of stimulation conditions. This suggests that the cells
      are end-stage cells. Taken together, the data suggest an increase in anergic or
      apoptotic CD8+ T cells in HIV-infected persons. Eventual depletion of HIV
      specific CD8+ T cells may occur through a process of proliferation, anergy
      induction, and apoptosis.

PMID- 7515929
TI  - Costimulation of tumor-reactive CD4+ and CD8+ T lymphocytes by B7, a natural
      ligand for CD28, can be used to treat established mouse melanoma.
AB  - Interactions between the costimulatory molecule B7 on APC and its counter
      receptor CD28 on T lymphocytes play a key role in the induction of cell-mediated
      immune responses. We studied the role of costimulation of tumor-reactive T cells
      by B7 in the immune destruction of the K1735-M2 mouse melanoma into which the
      gene encoding the human melanoma-associated Ag, p97, had been transfected.
      Previous work has demonstrated that the p97 transfectant cl62 is immunogenic but
      still grows progressively in immunocompetent C3H/HeN mice and that adoptive
      transfer of p97-specific CD4+ T cells can induce the regression of small
      established cl62 tumors metastatic to the lungs. We have now shown that
      expression of B7 in cl62 after retroviral-mediated gene transfer eliminated its
      ability to grow in immunocompetent mice but not in T cell-deficient nude mice.
      Mice immunized with B7-transduced p97+ cells had an increased activity of both
      CD4+ T cells, which could proliferate in response to the p97 Ag, and CD8+ CTL,
      which could lyse a broad spectrum of cultured syngeneic p97+ and p97- tumor lines
      but not allogeneic tumor lines or syngeneic lymphoblasts. Both CD4+ and CD8+ T
      cell subsets were required for tumor rejection, and the depletion of CD4+ T cells
      in vivo decreased the tumoricidal activity of CD8+ CTL. Treatment of mice bearing
      an 8-day established s.c. cl62 melanoma by i.p. injection of B7+ cells from 2A, a
      highly immunogenic p97 transfectant, resulted in complete tumor regression and
      cure, injection of B7- 2A cells did not. The therapeutic effect was specific for
      the cl62 tumor. Our results demonstrate that costimulation by B7 can amplify both
      CD4+ and CD8+ T cell responses against small tumors toward therapeutic benefit.

PMID- 7515931
TI  - Dissociation rate of antibody-gp120 binding interactions is predictive of V3
      mediated neutralization of HIV-1.
AB  - mAbs specific for the V3 loop of HIV-1 are capable of neutralizing laboratory
      strains of HIV-1 in vitro. In this report we use surface plasmon resonance and
      biosensor technology to demonstrate that the ability of V3-specific mAbs to
      neutralize HIV-1(MN) correlated with the dissociation rate constant of the
      homologous mAb-gp120 binding interaction. mAbs capable of binding diverse strains
      of gp120 with similar association rate constants exhibited marked differences in
      the dissociation rate. The dissociation rate, and not the association rate, was
      found to be predictive of the neutralization capacity of the mAb. Furthermore,
      synthetic peptides corresponding to the V3 loop of HIV-1(IIIB, MN) yielded
      quantitatively similar binding kinetic profiles abrogating the need for purified
      recombinant gp120 protein and potentially facilitating the screening of more
      diverse isolates. Biosensor immobilized V3 peptides were found to mimic their
      conformational structure in solution. This offers advantages to peptides studied
      by ELISA where some degree of denaturation and masking of epitopes can occur upon
      adsorption of peptides to plastic surfaces. The impact of amino acid
      substitutions within epitopes on subsequent mAb binding was dissected by
      observing alterations in dissociation rates. The technique provides rapid kinetic
      analyses of V3 Ab binding interactions with diverse V3 sequences, facilitating
      the efficient screening and selection of those most likely to possess the
      broadest and most potent HIV-1 neutralizing potentials.

PMID- 7515930
TI  - Soluble CTLA-4 can suppress autoantibody production and elicit long term
      unresponsiveness in a novel transgenic model.
AB  - Activation of Ag-specific T cells often requires costimulatory signals in
      addition to the primary signal mediated through the TCR. The CD28-B7 interaction
      provides one important costimulatory signal. Previous studies have shown that a
      soluble CD28 homologue, CTLA4lg, binds B7 with high affinity and can inhibit CD28
      B7-mediated costimulation in vitro and in vivo. In this study we examined the
      ability of soluble human CTLA4lg to inhibit autoantibody production in vivo. For
      this purpose we used a novel transgenic (Tg) model of autoantibody production.
      Hepatitis B eAg-expressing Tg mice can be induced to produce autoantibody to the
      circulating autoantigen (HBeAg) by the injection of a T cell recognition site
      that fails to elicit T cell tolerance in these mice. Autoimmunity in this model
      is quantitative because serum autoantibody and autoantigen concentration are
      inversely correlated and easily measurable by ELISA. In this system a single
      regimen of CTLA4lg treatment significantly suppressed primary autoantibody
      production and variably led to long term unresponsiveness. Furthermore, in vivo
      treatment with CTLA4lg inhibited both T cell activation and T cell-B cell
      interactions.

PMID- 7515932
TI  - CD45-mediated regulation of extracellular calcium influx in a CD4-transfected
      human T cell line.
AB  - Transfection of a CD4- Jurkat leukemic T cell line with the human wild-type CD4
      gene resulted in the constitutive mobilization of calcium by these cells. The
      altered calcium phenotype was dependent on expression of a completely functional
      CD4 molecule on the cell surface. Transfectants receiving the vector alone or
      those in which a mutated CD4 gene lacking a functional Lck binding region failed
      to generate a constitutive calcium response. In addition, CD4 wild-type
      transfectants over time lost CD4 expression. These CD4- revertants failed to
      constitutively mobilize calcium. Treatment of CD4 wild-type transfected cells
      with either anti-CD45 mAb, EGTA, or PMA rapidly restored the cells to basal
      levels of intracellular calcium. Analysis of CD45 cross-linking on CD4+ and CD4-
      normal Jurkat lines demonstrated that CD4 expression was required for CD45
      mediated inhibition of TCR induced calcium responses. CD45-mediated inhibition
      affected the duration of the response rather than its magnitude. These results,
      taken together with the observations obtained with CD4 transfected Jurkats
      suggested that influx of extracellular calcium was the predominant reason for the
      elevated levels of calcium within the cell. In support of this hypothesis, we
      could find no evidence of phosphorylated phospholipase C gamma 1 or constitutive
      inositol 1,4,5 trisphosphate generation in the CD4 wild-type transfected cells,
      yet both were detectable after anti-CD3 mAb-induced activation. Immunokinase
      assays of Lck and Fyn precipitated from untreated or anti-CD45-treated wild-type
      transfectants demonstrated that CD45 cross-linking dephosphorylated Lck and
      reduced its capacity to phosphorylate enolase. In contrast, neither Fyn
      autophosphorylation nor its activity was affected by CD45 cross-linking.

PMID- 7515935
TI  - The role of N-linked oligosaccharides of MHC class II antigens in T cell
      stimulation.
AB  - A specific increase in T cell extracellular acidification rate has been
      demonstrated recently when complexes of purified MHC class II molecules and
      antigenic peptides interact with T cell receptors (TCRs) on cloned T cells. The
      present study shows that such measurements of an increase in extracellular
      acidification rate can be used to evaluate the functional role of various N
      linked oligosaccharides of MHC class II antigens. Affinity-purified murine IAk
      and IAs were deglycosylated in the presence of aspargine-amidase enzyme and were
      characterized by SDS-polyacrylamide gel electrophoresis. The complete removal of
      all three N-linked oligosaccharides from the alpha/beta heterodimer was confirmed
      by four different lectin-linked Western blot analyses. Similar to the native
      heterodimer, both deglycosylated IAk and deglycosylated IAs were fully capable of
      binding synthetic antigenic peptides derived from myelin basic protein (MBP).
      When equivalent amount of glycosylated and deglycosylated class II-peptide
      complexes were exposed to restricted cloned T cells, identical increases in T
      cell extracellular acidification rates were observed. The specificity of such
      increases in extracellular acidification rate was demonstrated by exposing cloned
      T cells to irrelevant complexes of glycosylated and deglycosylated class II and
      antigenic peptides. These results show how measurement of extracellular
      acidification rate can be used to study structure-function correlations of ligand
      receptor interactions, and support an earlier observation that N-linked
      oligosaccharides of murine MHC class II molecules are not involved in either
      antigenic peptide binding or T cell recognition.

PMID- 7515934
TI  - Characterization of monoclonal antibodies to apolipoprotein (a) and development
      of a chemiluminescent assay for phenotyping apolipoprotein (a) isomorphs.
AB  - Apo(a) is linked to Lp(a) through non-covalent interactions and disulfide bond
      with apo B. Monoclonal antibodies were raised to reduced and carboxymethylated
      apo(a) in order to study apo(a) interaction with apo B and to develop a sensitive
      immunoassay for apo(a) and Lp(a). Nine antibodies were characterized for
      overlapping epitopes and for single or multiple binding sites on native Lp(a) or
      denatured apo(a). All monoclonal antibodies bound to Lp(a) and denatured apo(a)
      when these preparations were absorbed on polystyrene. In contrast, three
      antibodies (3D1, 4B4 and 6H9) failed to react with Lp(a) in solution, in a
      competitive displacement assay. This observation indicates that these epitopes
      are masked in native Lp(a). Cross-reactivity with plasminogen was noted for only
      one monoclonal antibody (4B4). An assay of competitive binding to immobilized
      Lp(a) or apo(a) revealed that four distinct groups of epitopes were recognized by
      the monoclonal antibodies: (A) 1G7, 3A5 partially overlapping with 8B6, (B) 5C4,
      5B10 partially overlapping with 7C1, (C) 3D1 overlapping with 6H9, and (D) 4B4. A
      double antibody sandwich assay, using homologous and heterologous combinations of
      monoclonal antibodies, showed that monoclonal antibodies 1G7, 3A5 and 8B6 of
      group A, and 5C4 and 5B10 of group B recognized multiple epitopes on Lp(a) while
      all other antibodies (3D1, 6H9, 4B4) recognized single epitopes. Based on reports
      of others for the sequence of apo(a), deduced from the cDNA of the human apo(a)
      gene, it is proposed that monoclonal antibodies which recognize multiple epitopes
      are directed toward the repetitive kringle 4-like domains of apo(a) while those
      recognizing single epitopes are probably directed to the kringle 5 or the
      protease-like domain of apo(a). Monoclonal antibodies which recognized repetitive
      epitopes were used for the development of a highly sensitive chemiluminescent
      immunoblotting system for detection of apo(a) isomorphs after resolving plasma
      protein by polyacrylamide (4%) gel electrophoresis in the presence of sodium
      dodecyl sulfate. Seven relatively common isomorphs were identified and readily
      resolved as a mixture. The detection limit was 5-10 pg for each apo(a) isomorph.
      The high sensitivity allowed for the detection of isomorphs present in over 99%
      of plasma samples despite a wide range of ratios of apo(a) isomorphs.

PMID- 7515933
TI  - Activation of src family kinases in human pre-B cells by IL-7.
AB  - IL-7 was identified originally as a specific pre-B cell growth factor. We have
      investigated its signal transduction mechanism by using the human pre-B cell line
      Nalm-6, and have found that it stimulates tyrosine phosphorylation of various
      proteins: pp27, pp43, pp54, pp64, pp78, pp90, pp105, and pp120.
      Antiphosphotyrosine immunoprecipitates from IL-7-stimulated Nalm-6 showed two
      major proteins of M(r) = 60,000 and 55,000, capable of autophosphorylation.
      Autophosphorylation was maximal 10 min after the cells were challenged with the
      cytokine. Antiphosphotyrosine immunoprecipitates from IL-7-stimulated cells also
      increased tyrosine phosphorylation of the exogenously added substrate histone
      H2B. Furthermore, by using a polyclonal anti-IL-7 receptor (IL-7R) Ab in Western
      blotting analysis, we observed that antiphosphotyrosine immunoprecipitates were
      associated with the IL-7R in a transient manner. These data indicate that the IL
      7R associates with tyrosine-phosphorylated proteins as its amino acid sequence is
      devoid of a putative site of tyrosine phosphorylation. These results were
      confirmed as several 32P-labeled proteins were visualized after
      immunoprecipitation by using anti-IL-7R Ab. Anti-IL-7R immunoprecipitates from IL
      7-stimulated cells revealed a unique band of M(r) = 60,000 associated with the
      receptor able to autophosphorylate in the presence of ATP and Mn2+. Hence, we
      identified p59fyn and p53/56lyn to be stimulated by IL-7. In contrast to
      p53/56lyn, p59fyn was found to be associated constitutively with the cloned IL
      7R. These data emphasize the role of the src family in hematopoiesis.

PMID- 7515936
TI  - S.C.S. effectiveness in patients affected by peripheral chronic arterial disease:
      our 5 years experience.
AB  - Spinal cord stimulation (S.C.S.) showed a valid clinical effect in the treatment
      of chronic obliterative arteriopathy of the lower limbs at an advanced stage (III
      IV stages) and of phantom limb pain syndrome (P.L.P.S.). Secretion patterns of
      various biochemical mediators were evaluated and mechanism, by which analgesic
      and vasodilatator actions occur, were thus accounted for. There is not agreement
      on this subject. We report our experience on 60 patients (age range 28-91),
      observed over the period 1987-92. Blood values of some chemical mediators (beta
      endorphins, Kinins, Serotonin, PGE) were determined before and after
      stabilization of the S.C.S. implant (from 2 up to 6 months) and compared with the
      objective clinical and TCpO2 data. Statistical significance was checked of
      variations obtained (Student's "t" test). High significant increase of TCpO2,
      beta-endorphins, PGE, (p < 0.01) and the Kinins (p < 0.05) was found but there
      were no significant alteration of Serotonin. Results are explained and an S.C.S.
      effect at the spinal cord metamer level with a cortical integration (pointed out
      by the increase of the beta-endorphins) is suggested. Analgesic effectiveness and
      vasodilatator action of S.C.S. implant is stressed as long as it is carried out
      only when a correct indication is established in the absence of contraindications
      or important risk.

PMID- 7515937
TI  - Rift Valley fever virus L segment: correction of the sequence and possible
      functional role of newly identified regions conserved in RNA-dependent
      polymerases.
AB  - The sequence of Rift Valley fever virus L segment that we published in a previous
      paper was erroneous in the 3'-terminal region of the antigenomic RNA molecule.
      Here, we have shown that the L segment is in fact 6404 nucleotides long and
      encodes a polypeptide of 237.7K in the viral complementary sense. Sequence
      comparisons performed between the RNA-dependent RNA polymerases of 22 negative
      stranded RNA viruses revealed the existence of two novel regions located at the
      amino termini of the proteins and conserved only in the polymerases of bunya- and
      arenaviruses. In the region conserved in all RNA-dependent polymerases,
      corresponding to the so-called 'polymerase module', we identified a new motif,
      designated premotif A, common to all RNA-dependent polymerases, as well as amino
      acids located in the region between motifs preA and A which are strictly
      conserved for segmented negative-stranded RNA viruses. Using the recently
      released coordinates of human immunodeficiency virus reverse transcriptase and
      the alignment between all RNA-dependent polymerases in the 'polymerase module',
      we have determined the position of the conserved residues in these polymerases
      and discuss their possible functions in light of the available structural
      information.

PMID- 7515939
TI  - Replication of the satellite RNA of pea enation mosaic virus is controlled by RNA
      2-encoded functions.
AB  - The helper virus mediating replication of the satellite RNA (RNA 3) of pea
      enation mosaic virus (PEMV) consists of two autonomously replicating,
      taxonomically unrelated viral RNAs with ties to the luteovirus (RNA 1) and the
      newly proposed umbravirus (RNA 2) genera. The following study dissects the
      relative contribution of each of the genomic RNAs of PEMV to the subsistence and
      dissemination of this satellite RNA. Infectivity assays in a pea protoplast
      system demonstrate that RNA 2 alone is responsible for the replication of RNA 3,
      an observation that is supported in part by shared regions of sequence homology
      at the 5' and 3' termini of both RNAs. In pea seedlings, infectivity assays also
      demonstrated that the presence of RNA 2 alone is necessary for the systemic
      invasion of RNA 3. In contrast, the luteovirus-like phase of PEMV (RNA 1) is
      solely responsible for the encapsidation and aphid transmission of both RNA 2 and
      the satellite RNA. In a manner comparable to several other virus-satellite
      systems, the satellite of PEMV also displays a differential response in its
      capacity to attenuate symptom expression in selected host species. Thus, the
      satellite RNA of PEMV exists in a trilateral arrangement with its host and two
      viral RNAs, comparable in many respects to the satellite-virus-host interaction
      occurring with groundnut rosette disease.

PMID- 7515938
TI  - Infection of human macrophages with an endogenous tumour necrosis factor-alpha
      (TNF-alpha)-independent human immunodeficiency virus type 1 isolate is
      unresponsive to the TNF-alpha synthesis inhibitor RP 55778.
AB  - Monocyte-derived macrophages (MDM) were demonstrated to be susceptible to
      productive infection by the monocytotropic human immunodeficiency virus type 1
      (HIV-1) strain HIV-1/Ba-L and by three primary HIV-1 isolates, HIV-1/DAS, HIV
      1/PAR and HIV-1/THI. Production of tumour necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6) and IL-1 beta was monitored between days 3 and 26 after MDM
      infection. TNF-alpha and IL-6 were detected in cell culture supernatants from
      days 16 to 21 following HIV-1/DAS, HIV-1/PAR and HIV-1/Ba-L infection, at the
      time of high viral replication. IL-1 beta was not found at the same time points.
      TNF-alpha mRNA expression occurred around the peak of both TNF-alpha levels and
      supernatant RT activities. In HIV-1/THI-infected macrophage cultures no
      endogenously produced TNF-alpha was observed, despite high levels of HIV-1 in
      MDM. This result demonstrates that a primary isolate may replicate independently
      of TNF-alpha in MDM. To investigate the relationship between TNF-alpha and viral
      replication we used a TNF-alpha synthesis inhibitor, RP 55778. Treatment
      throughout the course of cell culture resulted in a significant decrease in both
      TNF-alpha levels and viral production in HIV-1/DAS-, HIV-1/PAR- and HIV-1/Ba-L
      infected MDM cultures. This phenomenon is reversed by adding recombinant human
      TNF-alpha to the RP 55778-treated cell cultures from day 14 post-infection. No
      effect of RP 55778 was observed in MDM cultures infected with the primary isolate
      HIV-1/THI, whose replication is independent of TNF-alpha production and therefore
      remained unchanged after RP 55778 treatment. We conclude that the clinical value
      of such a drug is directly dependent on the ability of the HIV-1 strains involved
      to induce TNF-alpha production at the time of viral replication.

PMID- 7515940
TI  - Expression of the beet yellows closterovirus capsid protein and p24, a capsid
      protein homologue, in vitro and in vivo.
AB  - The positive-sense RNA genome of beet yellows closterovirus (BYV) encompasses
      open reading frames (ORFs) for the viral capsid protein (CP, ORF 6) and for a CP
      homologue (p24, ORF 5). The sequences of the ORFs 5 and 6 were inserted into an
      Escherichia coli expression vector, pQE-9, under the control of the bacteriophage
      T5 promoter. The proteins were expressed in bacteria, purified, and used for
      antiserum production in rabbits. The recombinant BYV CP and p24 showed
      serological cross-reactions when probed with each antiserum on Western blots. The
      cross-reactions of the anti-p24 serum with the CP, and of the anti-CP serum with
      the p24, were abolished by preadsorption with the heterologous antigens,
      suggesting that CP and p24 share a common epitope(s) resistant to SDS
      denaturation. Cross-reactivity of the soluble CP and p24 was also observed in
      indirect plate-trapped antigen ELISA, whereas virtually none was encountered in
      double-antibody sandwich ELISA. Using a polyclonal anti-p24 serum preadsorbed
      with the recombinant CP, the p24 was detected in BYV-infected plants. Analysis of
      subcellular fractions of BYV-infected Tetragonia expansa indicated that both
      proteins are predominantly located in the soluble fraction of the host cells.
      Primer extension analysis of the individual double-stranded forms of the
      subgenomic RNAs bearing the CP and p24 genes allowed them to be mapped and their
      5' start sites to be located at nucleotide positions 13,588 and 12,815,
      respectively, in the complete genome sequence. This corresponds to the 5'
      untranslated regions of 52 and 105 nucleotides in the subgenomic RNAs for CP and
      p24, respectively. The data obtained indicate that the synthesis of both
      subgenomic RNAs is initiated on a negative RNA strand at an adenosine residue
      found within the conserved sequence 5' CCAUUUPyA (shown as positive-sense), which
      may thus represent a core element of the subgenomic promoter. This conserved
      sequence also resembles the sequences at the 5' ends of the CP subgenomic RNAs of
      tobamoviruses and the Bromoviridae family members, the viruses evolutionarily
      most closely related to BYV.

PMID- 7515941
TI  - Melatonin receptor-mediated inhibition of cyclic AMP accumulation in chick
      retinal cell cultures.
AB  - Melatonin receptors were characterized in cultured neurons and photoreceptors
      prepared from chick embryo retina. Cultured cells contained high-affinity 2
      [125I]iodomelatonin binding sites (KD = 41.6 pM), similar to those in intact
      retina. The effects of melatonin and related indoles on cyclic AMP accumulation
      were examined. Melatonin (10(-7) M) had no effect on basal or K(+)-stimulated
      cyclic AMP accumulation, but inhibited forskolin-stimulated cyclic AMP
      accumulation by approximately 50%. Melatonin inhibited forskolin-stimulated
      cyclic AMP accumulation in the presence or absence of the cyclic nucleotide
      phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, suggesting an effect on
      cyclic AMP synthesis rather than degradation. Half-maximal inhibition was
      observed at 5.9 x 10(-10) M melatonin. The relative order of potency among
      melatonin analogues was 2-iodomelatonin > melatonin approximately 6
      chloromelatonin > or = 6-hydroxymelatonin > N-acetylserotonin approximately 5
      methoxytryptophol > serotonin. The EC50 value for inhibition of cyclic AMP
      accumulation by 2-iodomelatonin (36.7 pM) was comparable to the KD value for
      binding of the radioligand, suggesting that the binding sites represent
      functional receptors. The inhibitory effect of melatonin was antagonized by the
      putative melatonin antagonists luzindole, N-acetyltryptamine, and N-(2,4
      dinitrophenyl)-5-methoxytryptamine, with estimated KB values of 0.12, 0.17, and 1
      microM, respectively. At a concentration of 10 microM, N-(2,4-dinitrophenyl)-5
      methoxytryptamine significantly inhibited forskolin-stimulated cyclic AMP
      accumulation when added alone; at 30 microM, luzindole and N-acetyltryptamine
      also had significant inhibitory effects. The inhibitory effect of melatonin was
      blocked by pretreatment with pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515945
TI  - Characterization of basal and morphine-induced histamine release in the rat
      periaqueductal gray.
AB  - Previous studies have shown that antinociceptive doses of systemic morphine
      increase extracellular histamine (HA) levels in the rat periaqueductal gray
      (PAG), although the cellular origin of basal and morphine-induced HA release in
      the PAG is unknown. Treatment with alpha-fluoromethylhistidine (FMH; 100 mg/kg,
      i.p.), the irreversible inhibitor of histidine decarboxylase, decreased basal HA
      release by a maximum of 80% and prevented morphine-induced HA release in the PAG.
      In addition, perfusion of this area with the sodium channel blocker tetrodotoxin
      (10(-6) M) decreased basal HA release by a maximum of 57% from baseline levels.
      When the perfusion medium was modified by substitution of magnesium for calcium,
      extracellular HA levels in the PAG decreased by a maximum of 72%, and morphine
      induced HA release was prevented. Thioperamide (5 mg/kg, i.p.), an H3 antagonist,
      increased HA release in the PAG to a maximum of 249% within the first 30-60-min
      period. Taken together, these results suggest that basal and morphine-induced HA
      release in the rat PAG have a neuronal origin.

PMID- 7515942
TI  - Expression of two types of nitric oxide synthase mRNA in human neuroblastoma cell
      lines.
AB  - Expression of nitric oxide synthase (NOS) was studied in nine human neuroblastoma
      and two human glioblastoma cell lines. Neuronal NOS (n-NOS) mRNA of approximately
      10 kb was detected in four of the nine neuroblastoma cell lines by northern blot
      analysis using human n-NOS cDNA as a probe. Expression of the n-NOS mRNA was also
      detected in another neuroblastoma cell line in a subsequent reverse transcriptase
      polymerase chain reaction (RT-PCR) study, but no n-NOS mRNA expression was
      observed in the other four neuroblastoma cell lines or in the glioblastoma cell
      lines. The level of NOS activity correlated well with that of n-NOS mRNA
      expression in neuroblastoma cell lines expressing n-NOS mRNA. Western blot
      analysis showed that the n-NOS expressed in neuroblastoma cells was a 160-kDa
      protein reacted with anti-n-NOS antibody. By using the RT-PCR method, a short n
      NOS (n-NOS-2) mRNA with a 315-bp inframe deletion from the entire n-NOS (n-NOS-1)
      mRNA was detected in the human neuroblastoma cells. The structural diversity of
      human n-NOS mRNA was demonstrated for the first time.

PMID- 7515944
TI  - Cyclothiazide selectively potentiates AMPA- and kainate-induced
      [3H]norepinephrine release from rat hippocampal slices.
AB  - Activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA) subtype of ionotropic glutamate receptors has been shown to result in a
      rapid desensitization of the receptor in the presence of certain agonists. One
      effect of AMPA receptor desensitization in the hippocampus may be to decrease the
      efficacy of AMPA receptor agonists at stimulating the release of norepinephrine
      from noradrenergic terminals. Recently, cyclothiazide was reported to inhibit
      AMPA receptor desensitization by acting at a distinct site on AMPA receptors. We
      have examined the effect of cyclothiazide on AMPA- and kainate (KA)-induced
      norepinephrine release from rat hippocampal slices to determine whether
      cyclothiazide would increase the efficacy of AMPA-induced [3H]norepinephrine
      release by inhibiting AMPA receptor desensitization. Cyclothiazide was observed
      to potentiate markedly both AMPA- and KA-induced [3H]-norepinephrine release.
      This potentiation is selective for AMPA/KA receptors as cyclothiazide did not
      potentiate N-methyl-D-aspartate-induced [3H]norepinephrine release or release
      induced by the nonspecific depolarizing agents veratridine and 4-aminopyridine.
      These results demonstrate that AMPA receptor-mediated modulation of
      [3H]norepinephrine release from rat brain slices is a useful approach to studying
      the cyclothiazide modulatory site on the AMPA receptor complex.

PMID- 7515943
TI  - Alpha 2-adrenoceptor-mediated inhibition of electrically evoked [3H]noradrenaline
      release from chick sympathetic neurons: role of cyclic AMP.
AB  - This study explores the role of cyclic AMP in electrically evoked
      [3H]noradrenaline release and in the alpha 2-adrenergic modulation of this
      release in chick sympathetic neurons. Along with an increase in stimulation
      evoked tritium overflow, applications of forskolin enhanced the formation of
      intracellular cyclic AMP. Both effects of forskolin were potentiated by the
      phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The forskolin-induced
      increase in overflow was abolished by the Rp-diastereomer of cyclic AMP-thioate,
      an antagonist at cyclic AMP-dependent protein kinases, and 1,9-dideoxy-forskolin,
      an inactive analogue at adenylyl cyclase, had no effect on the evoked overflow. A
      24-h pretreatment with either cholera toxin or forskolin reduced the subsequent
      forskolin-induced accumulation of cyclic AMP and inhibited the stimulation-evoked
      release. Basal cyclic AMP production, however, remained unaltered after forskolin
      treatment and was enhanced after 24 h of cholera toxin exposure. The alpha 2
      adrenergic agonist bromoxidine did not affect the formation of cyclic AMP
      stimulated by forskolin but reduced electrically evoked release. However, effects
      of bromoxidine on 3H overflow were attenuated by forskolin as well as by 8-bromo
      cyclic AMP. Effects of bromoxidine on [3H]noradrenaline release were paralleled
      by an inhibition of voltage-activated Ca2+ currents, primarily through a delayed
      time course of current activation. This effect was abolished when either
      forskolin or 8-bromo-cyclic AMP was included in the pipette solution. Both
      substances, however, failed to affect Ca2+ currents in the absence of
      bromoxidine. These results suggest that the signaling cascade of the alpha 2
      adrenergic inhibition of noradrenaline release involves voltage-activated Ca2+
      channels but not cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515947
TI  - A novel cyclic AMP response element, CACTTGATC, mediates forskolin induction of
      the myelin basic protein promoter in the rat Schwannoma line, D6P2T.
AB  - The rat Schwannoma cell line D6P2T constitutively expresses the mRNA encoding the
      major myelin protein, P0, but only expresses the mRNA encoding myelin basic
      protein (MBP) after exposure to forskolin or other substances that raise the
      levels of intracellular cyclic AMP. In this study we have investigated the
      molecular basis for forskolin induction of MBP transcription in D6P2T cells. We
      have found that a 9-bp sequence element, CACTTGATC, located between nucleotides 
      85 and -77 in the MBP promoter, is necessary for forskolin induction of
      chloramphenicol acetyltransferase (CAT) expression after transient transfection
      of MBP promoter-CAT fusion constructs into D6P2T cells. Although similar DNase I
      footprints, one of which is located within the above 9-bp sequence element, are
      produced by nuclear extracts prepared from both forskolin-treated and untreated
      cells, this same sequence can be shown to interact with a forskolin-inducible
      protein complex using an electrophoretic mobility shift assay. In addition,
      mutation of this 9-bp sequence abolishes both formation of this new protein--DNA
      complex and forskolin-inducible CAT expression from the heterologous SV40
      promoter. Finally, we have shown that the appearance of this forskolin-inducible
      protein--DNA complex precedes that of MBP mRNA. Taken together, these data
      strongly support the notion that the induction of MBP transcription by forskolin
      in D6P2T cells is mediated by the binding of a forskolin-inducible protein
      complex to the MBP promoter sequence CACTTGATC.

PMID- 7515949
TI  - Antipeptide polyclonal antibodies that recognize a substance P-binding site in
      mammalian tissues: a biochemical and immunocytochemical study.
AB  - We used complementary peptide methodology to obtain antibodies against the
      receptor for the neuropeptide substance P, specifically directed at the ligand
      binding domain. Rabbits were immunized with two distinct peptides derived from
      the sequence of the RNA complementary to the mRNA for substance P. Binding
      experiments revealed that antipeptide polyclonal antibodies were able to
      recognize, through their paratope, a specific binding site on the rat parotid
      cell membranes. Substance P and antibodies competed for this binding site,
      because preincubation of membranes in the presence of substance P significantly
      reduced antibody binding, and conversely, preincubation of membranes in the
      presence of antibodies partly inhibited the binding of radioiodinated substance
      P. Immunocytochemical experiments performed on the rat cervical spinal cord show
      that the distribution of labeling by antibodies is similar to that observed by
      conventional autoradiography using 125I-substance P. Here again, control
      experiments demonstrated that antibodies and substance P were competing for the
      same binding site on the spinal cord. These biochemical and immunocytochemical
      data indicate that antipeptide antibodies recognize a substance P membrane
      binding site in nervous and nonnervous mammalian tissues. This site is likely to
      correspond to the NK1 specific receptor for substance P.

PMID- 7515946
TI  - Localization and developmental changes of tau protein kinase I/glycogen synthase
      kinase-3 beta in rat brain.
AB  - tau protein kinase I (TPKI) purified from bovine brain extract has been shown to
      phosphorylate tau and to form paired helical filament (PHF) epitopes and was
      found recently to be identical to glycogen synthase kinase -3 beta (GSK-3 beta).
      Before elucidating a role of TPKI/GSK-3 beta in PHF formation, it is necessary to
      investigate the normal function of the enzyme. To study the distribution and
      developmental changes of the enzyme, specific polyclonal antibodies were prepared
      against TPKI and GSK-3 alpha. Immunoblot analysis demonstrated that TPKI was
      nearly specifically localized in the brain of adult rats. The level of TPKI in
      the rat brain was high at gestational day 18, peaked on postnatal day 8, and then
      decreased rapidly to a low level, which was sustained up to 2 years.
      Immunohistochemistry indicated primarily neuronal localization of TPKI. Growing
      axons were stained most intensely in the developing cerebellum, but the
      immunoreactivity became restricted to the gray matter in the mature tissue.
      Parallel fibers had a high level of TPKI and also stained intensely for tau.
      These findings indicate that tau is one of the physiological substrates of TPKI
      and suggest that the enzyme plays an important role in the growth of axons during
      development of the brain.

PMID- 7515948
TI  - Induction and regulation of nitric oxide synthase in retinal Muller glial cells.
AB  - Muller glial cells from the rat retina were examined for their capacity to
      produce nitric oxide (NO). Treatment of retinal Muller glial (RMG) cells with
      lipopolysaccharide (LPS), interferon-gamma, and tumor necrosis factor-alpha
      induced NO synthesis as determined by nitrite release in media. Simultaneous
      addition of LPS, interferon-gamma, and tumor necrosis factor-alpha caused the
      largest increase in NO synthesis. NO biosynthesis was detected after 12 h and was
      dependent on the dose of LPS, interferon-gamma, and tumor necrosis factor-alpha.
      Stereoselective inhibitors of NO synthase (NOS), cycloheximide and transforming
      growth factor-beta, blocked cytokine-induced NO production. Cytosol from
      LPS/cytokine-treated RMG cultures, but not from unstimulated cultures, produced a
      calcium/calmodulin-independent conversion of L-arginine to L-citrulline that was
      completely blocked by NOS inhibitor. The expression of NOS in RMG cells was
      confirmed by northern blot analysis, in which stimulation of these cells led to
      an increase in NOS mRNA levels. We conclude that RMG cells can express an
      inducible form of NOS similar to the macrophage isoform. High NO release from
      activated RMG cells might represent a protection from infection but may also
      contribute to the development of retinal pathologies.

PMID- 7515950
TI  - ADP-ribosylation of human myelin basic protein.
AB  - When isolated myelin membranes were ADP-ribosylated by [32P]NAD+ either in the
      absence of toxin (by the membrane ADP-ribosyltransferase) or in the presence of
      cholera toxin, the same proteins were ADP-ribosylated in both cases and myelin
      basic protein (MBP) was the major radioactive product. Therefore, cholera toxin
      was considered a good model for ADP-ribosylation of myelin proteins. Although
      purified human MBP migrates as a single band on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with a molecular mass of 20 kDa, the
      microheterogeneity that is masked under these conditions can be clearly
      demonstrated on alkaline-urea gels at pH 10.6. At this pH, MBP is resolved into
      several components that differ one from the other by a single charge (charge
      isomers). These charge isomers can be resolved on CM52 columns at pH 10.6, and
      several can be ADP-ribosylated. Component 1 (C-1), the most cationic charge
      isomer, incorporated 1.79 mol of ADP-ribose/mol of protein. C-2 and C-3 (which
      differ from C-1 by the loss of one and two positive charges, respectively)
      incorporated slightly less at 1.67 and 1.63 mol of ADP-ribose/mol of protein,
      respectively, whereas C-8, the least cationic, incorporated less than 0.11
      mol/mol of protein. In the presence of neutral hydroxylamine, the ADP-ribosyl
      bond was shown to have a half-life of about 80 min, suggesting an N-glycosidic
      linkage between ADP-ribose and an arginyl residue of the protein.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7515951
TI  - Formation of a disulfide bond in the immunoglobulin domain of the myelin P0
      protein is essential for its adhesion.
AB  - It is widely accepted, although never demonstrated, that the formation of a
      disulfide bond in the majority of immunoglobulin (Ig)-like domains stabilizes
      their final conformation and thus is essential to their functioning as
      adhesion/recognition molecules. The myelin P0 protein, which has been shown
      directly to behave as a homophilic adhesion molecule, contains a single Ig-like
      domain, stabilized by a putative Cys21-Cys98 disulfide bond. To test if this bond
      is indeed necessary to the adhesive function of P0, the nucleotides in the P0
      cDNA coding for Cys21 were altered to code for an alanine. The mutated P0 cDNA
      was transfected into Chinese hamster ovary cells, expression of the mutated P0
      protein was characterized, and the adhesiveness of Cys21-mutated P0-expressing
      cells and that of cells expressing equivalent surface amounts of the unmutated
      protein were compared. It was found, as we previously reported, that incubation
      of a single cell suspension of the unmutated P0-expressing cells resulted in the
      rapid formation of large aggregates. In contrast, after a similar incubation the
      cells expressing the Cys21-mutated P0 were still mostly single cells, a result
      indistinguishable from that observed with the control transfected cells. This
      suggests that the P0 protein, when mutated at Cys21, does not behave as a
      homophilic adhesion molecule, which in turn implies that the formation of an Ig
      domain disulfide bond is essential to the functioning of this molecule.

PMID- 7515953
TI  - Intraventricular administration of BDNF increases neuropeptide expression in
      newborn rat brain.
AB  - Brain-derived neurotrophic factor (BDNF) specifically enhances and maintains the
      expression of neuropeptide Y (NPY) and somatostatin (SOM) in cultured neocortical
      neurons (Nawa et al., 1993). In this article, we examined its effects in vivo on
      neuropeptide expression in various brain regions by injecting BDNF into the
      cerebroventricle of newborn rats. Repeated administration (2x) of BDNF increased
      contents of NPY-like immunoreactivity (NPY-LI) and substance P (SP)-LI most
      markedly in the anterior neocortex by 11- and 24-fold, respectively, in
      comparison to values in the animals receiving control injection. A smaller but
      significant increase was also observed in immunoreactivity for somatostatin
      (SOM), enkephalin (ENK), and cholecystokinin (CCK). mRNA for NPY, SP, and SOM was
      similarly upregulated in the anterior neocortex, suggesting that BDNF enhances
      peptide synthesis rather than inhibiting peptide release or degradation. Among
      the brain regions examined, however, peptidergic responses to BDNF were different
      with respect to their spatial distribution and time course. Induction of SP-LI,
      NPY-LI, and SOM-LI around the injection site was most pronounced in cortical
      layers II/III, layers IV-VI, and layer VI, respectively. Peptidergic
      immunoreactivity was also enhanced in other brain regions ipsilateral to the
      injection site, for example, NPY-LI in the hippocampus, thalamic nuclei, and
      striatum, and SOM-LI in the striatum. A single injection of BDNF elevated SP-LI
      to a plateau level within 12 hr while NPY-LI and SOM-LI reached maximum levels at
      48 hr, and then all returned to control levels at 68 hr. In contrast, the same
      dose of NGF had no influences on the neuropeptide levels at 48 hr. These
      observations suggest that BDNF regulates the development of neuropeptide
      expression in the CNS in a plastic manner.

PMID- 7515952
TI  - Hypomyelinating peripheral neuropathies and schwannomas in transgenic mice
      expressing SV40 T-antigen.
AB  - We have prepared transgenic mice carrying a temperature-sensitive mutant of the
      SV40 oncogene (tsA-1609) under the control of 5' flanking sequences from the
      Schwann cell-specific P0 gene. Four of six founder mice showed moderate to severe
      hypomyelination in peripheral nerves of tail biopsies, with only rare myelinated
      fibers. Offspring were obtained from three of these founders. Northern blot and
      immunohistochemical analyses showed that expression of T-antigen was restricted
      to the PNS. Mice expressing the highest levels of T-antigen exhibited the most
      severe hypomyelination. Mice expressing lower levels developed transient mild
      hypomyelination, but after long latencies developed sporadic schwannomas. An
      immortalized cell line exhibiting properties of Schwann cells at an arrested
      stage of differentiation, termed "SCT-1," was derived from one of these tumors.

PMID- 7515954
TI  - Willardiines differentiate agonist binding sites for kainate- versus AMPA
      preferring glutamate receptors in DRG and hippocampal neurons.
AB  - Concentration jump responses to 5-substituted (S)-willardiines were recorded from
      dorsal root ganglion (DRG) and hippocampal neurons under voltage clamp. After
      block of desensitization by concanavalin-A, dose-response analysis for activation
      of kainate-preferring receptors in DRG neurons gave the potency sequence
      trifluoromethyl > iodo > bromo approximately chloro > nitro approximately cyano >
      kainate > methyl > fluoro > (R,S)-AMPA >> willardiine; EC50 values for the most
      and least potent willardiine derivatives, 5-trifluoromethyl (70 nM) and 5-fluoro
      (69 microM), differed 1000-fold. The potency sequence for equilibrium responses
      at AMPA-preferring receptors in hippocampal neurons was strikingly different from
      that obtained in DRG neurons: fluoro > cyano approximately trifluoromethyl
      approximately nitro > chloro approximately bromo > (R,S)-AMPA > iodo >
      willardiine > kainate > methyl. In hippocampal neurons EC50 values for the most
      and least potent willardiine derivatives, 5-fluoro (1.5 microM) and 5-methyl (251
      microM), differed only 170-fold. Consistent with equilibrium potency
      measurements, in DRG neurons the kinetics of deactivation for willardiines,
      recorded following a return to agonist-free solution, were rapid for 5-fluoro
      (tau off = 43 msec) but slow for 5-iodo (tau off = 4.2 sec), while the opposite
      sequence was observed for hippocampal neurons, slow for 5-fluoro (tau off = 2.1
      sec) and rapid for 5-iodo (tau off = 188 msec). The kinetics of recovery from
      desensitization showed comparable agonist- and cell-dependent differences.
      Structure-activity analysis for agonist responses recorded from DRG and
      hippocampal neurons suggests that for both kainate-preferring and AMPA-preferring
      receptors the binding of willardiines involves interactions with polar groups
      such that potency is related to ionization of the uracil ring, and hence the
      electron-withdrawing ability of the 5-position substituent. However, kainate
      preferring receptors differ from AMPA-preferring receptors in possessing a
      lipophilic pocket that further enhances agonist potency by hydrophobic bonding of
      the 5-substituent. In contrast, AMPA-preferring receptors lack such a lipophilic
      site, and for 5-position substituents of the same electron-withdrawing ability,
      potency decreases with increase in size.

PMID- 7515955
TI  - The role of hemispherectomy in the treatment of holohemispheric
      hemimegaloencephaly.
AB  - The role of hemispherectomy in treating holohemispheric hemimegaloencephaly, a
      unilateral brain malformation, is still not well defined. The authors describe
      the cases of five infants presenting with intractable seizures, progressive
      neurological deficits, and severe developmental delay. Electroencephalography
      (EEG) showed generalized polyspikes from the megaloencephalic hemisphere and
      progressive slowing on the opposite side in all children; contralateral seizure
      spikes occurred in three children. Three of the five children underwent
      hemispherectomy for intractable seizures before 2 years of age, after which the
      seizures subsided completely in two children and improved remarkably in the
      third. Preoperative Wada testing proved useful in evaluating pharmacologically
      the effect of hemispherectomy on contralateral polyspikes. Postoperative EEG
      revealed the absence of polyspikes in the operated hemisphere and decreased
      slowing on the contralateral side. Psychomotor development in the surgically
      treated infants exceeded that of the children not undergoing hemispherectomy. Of
      the two children treated medically, one died at 4 years of age in status
      epilepticus and the other (now 5 years old) has frequent seizures and severe
      developmental delay. Based on these results, hemispherectomy appears to be a
      useful procedure for controlling seizures and improving psychomotor development
      in children with hemimegaloencephaly involving the entire hemisphere. Surgery in
      infancy can prevent or minimize seizure foci and encephalopathic changes that may
      develop in the contralateral hemisphere. Staging the procedure and exercising
      meticulous hemostasis make surgery relatively safe in infants who otherwise may
      have significant blood loss associated with increased blood flow to the
      megaloencephalic hemisphere.

PMID- 7515956
TI  - Do the differences between the amino acid compositions of acute-phase and muscle
      proteins have a bearing on nitrogen loss in traumatic states?

PMID- 7515957
TI  - Integrin common chain beta 1 immunoreactivity in hepatocellular carcinoma.

PMID- 7515958
TI  - Plasma amylase levels as a marker of disease severity in an isogenic murine model
      of paracoccidioidomycosis.
AB  - Survival patterns after peritoneal infection with Paracoccidioides brasiliensis
      vary according to the mouse strain and to the virulence of the fungal isolate. It
      has previously been observed that a significant increase in plasma amylase levels
      occurs only when susceptible mice (B10.A) were infected with a virulent isolate
      (Pb18). In order to verify if increased amylase levels correlate with
      susceptibility to P. brasiliensis infection, 12 mouse strains with different
      susceptibility patterns to this fungus were investigated after infection with
      Pb18. When compared with their respective controls, C57BI/6, B10D2/oSn,
      B10D2/nSn, C3H/HeJ, B10.A and BALB/c mice showed a conspicuous amylase increase
      and AKR, (NZB x NZW)F1, CBA/J, (A/Sn x B10.A)F1, A/Sn and DBA/2 absence of
      alteration. The influence of the infecting fungal isolate on this enzymatic
      parameter was investigated using B10.A mice and fungal isolates with diverse
      degrees of virulence. When compared with their non-infected controls, mice
      infected with Pb45 or Pb47 showed a very high amylase increase, with Pb44 or Pb18
      a high one and with Pb50 or Pb265 a discrete increase. On the whole, there is an
      inverse correlation between survival times after infection and the increase in
      amylase levels. Thus, measurement of plasma amylase is a satisfactory parameter
      to evaluate the severity of paracoccidioidomycosis in mice.

PMID- 7515959
TI  - Nature of the reactive epitopes in Paracoccidioides brasiliensis polysaccharide
      antigen.
AB  - Fava Nettos' polysaccharide antigen (FNPA), shown to detect humoral and cellular
      responses in paracoccidioidomycosis, was investigated. Skin tests with FNPA were
      negative after alkaline hydrolysis or depletion of gp43 peptide epitopes.
      Purified antibodies to FNPA or gp43 from paracoccidioidomycosis patients cross
      reacted, showing common epitopes and FNPA-specific ones. Normal human sera, in
      contrast to paracoccidioidomycosis sera, were unreactive with gp43 but recognized
      epitopes of FNPA susceptible to alkaline hydrolysis and pronase treatment.
      Histoplasmosis patients sera strongly reacted with FNPA carbohydrate epitopes.

PMID- 7515960
TI  - Cytokeratin profile of the junctional epithelium in partially erupted teeth.
AB  - This study uses cytokeratins (CK) as markers to investigate the phenotype of the
      junctional epithelium (JE) in partially erupted human teeth. The gingival
      samples, which were clinically healthy, were carefully dissected from the teeth.
      Cryostat sections were cut for histological staining, immunofluorescence
      microscopy and gel electrophoresis. Cytokeratins were extracted after
      microdissection. The basal and suprabasal epithelial cell markers, cytokeratins
      4, 5, 13, 14 and 19 were detected with specific monoclonal antibodies. They
      showed that the junctional epithelium in erupting teeth has a complex topography.
      The cytokeratin immunohistochemical profile distinguished between the primary
      junctional epithelium (CK 5, 14 and 19 in basal and suprabasal cells and CK 13
      faintly stained throughout the suprabasal layers) and the adjacent epithelium
      that had the same cytokeratin profile as the sulcular epithelium (CK 5, 14 and 19
      in basal cells and CK 4 and 13 intensively stained in the suprabasal cells).
      Extraction, two-dimensional electrophoresis and western blotting showed that this
      transitional JE during eruption also contained CK 6, 16 and perhaps CK 4. Thus,
      the JE in erupting teeth shows patterns of CK distribution that are very similar
      to that of developing oral epithelia.

PMID- 7515961
TI  - Acute-phase proteins in gingival crevicular fluid during experimentally induced
      gingivitis.
AB  - The dynamics of four acute-phase proteins were investigated in gingival
      crevicular fluid (GCF) during the course of a 21 day experimental gingivitis
      study. These acute-phase proteins were the protease inhibitors alpha 2
      macroglobulin (alpha 2-M) and alpha 1-antitrypsin (alpha 1-AT) and the iron
      binding proteins transferrin (TF) and lactoferrin (LF). 6 healthy volunteers
      ceased all oral hygiene procedures for 3 weeks. GCF was sampled at seven day
      intervals from two sites per subject by paper strips for 30 s during the
      experimental gingivitis period and for two additional weeks after the
      reinstitution of oral hygiene. The mainly serum derived alpha 2-M, alpha 1-AT and
      TF exhibited very similar dynamics which reflects their common origin in GCF.
      Their levels increased significantly from baseline and remained high for at least
      one week after the reinstitution of oral hygiene measures (repeated measures
      MANOVA; alpha 2-M: p = 0.015; alpha 1-AT: p = 0.012; TF: p = 0.02). This probably
      reflects increased vascular permeability in the gingivae and, to a lesser degree,
      local production by gingival inflammatory cells. In contrast to the serum derived
      acute-phase proteins, the neutrophil derived LF rose significantly from baseline
      (repeated measures MANOVA; p = 0.001) but dropped rapidly after the reinstitution
      of oral hygiene measures. This could be because dental plaque was removed and
      thus neutrophil chemotactic agents in the crevice were decreased.

PMID- 7515962
TI  - Comparative histochemical, biochemical and immunocytochemical studies of
      cathepsin B in human gingiva.
AB  - Cathepsin B activity was demonstrated histochemically in unfixed cryostat
      sections of inflamed human gingiva using the 2-methoxy-4-naphthylamide (MNA)
      substrates Z-Val-Lys-Lys-Arg-MNA and Z-Ala-Arg-Arg-MNA with a post-azo-coupling
      technique. Enzyme localisation was confirmed by immunocytochemistry with
      polyclonal sheep anti-human cathepsin B. In both cases, staining was found in
      connective tissue fibroblasts and also in cells varying in shape from rounded to
      more irregular forms. The latter were present both in areas of cellular
      infiltration and in the oral and pocket epithelium. Examination of adjacent
      sections with monoclonal antibodies directed against leukocyte differentiation
      antigens showed that the rounded to irregular cells were CD68 positive
      macrophages and monocytes. The histochemical staining had the form of fine
      cytoplasmic particles consistent with the known lysosomal occurrence of cathepsin
      B. Cells stained by the post-coupling method using the tryptase substrates Z-Ala
      Ala-Lys-MNA and D-Val-Leu-Arg-MNA showed a different distribution and morphology,
      with reaction product confined to mast cell granules. The differences between the
      cathepsin B and tryptase staining patterns were confirmed by differential
      extraction from cryostat sections with salt-free and high-salt buffers
      respectively. Biochemical characterisation of activities in the extracts with the
      7-amino-4-trifluoromethyl coumarin (AFC) substrates Z-Val-Lys-Lys-Arg-AFC and Z
      Ala-Ala-Lys-AFC and protease inhibitors confirmed the identity of the two
      enzymes. Selective inhibitors could also be used in histochemical incubations to
      distinguish between cathepsin B and tryptase staining.

PMID- 7515963
TI  - Polysaccharide production in Pseudomonas cepacia.
AB  - The effects of glucose, osmolarity, temperature and mode of growth on
      exopolysaccharide production in Pseudomonas cepacia was studied in batch culture
      using a chemically defined growth medium. Polymer production was maximal under
      conditions of a 2% (w/v) glucose supplement, 0.4 M NaCl and an incubation
      temperature of 35 degrees C. In addition, polysaccharide composition and
      molecular weight varied with mode of growth. On agar culture there was a decrease
      in pyruvate and rhamnose content yet an increase in the amount of acetate
      compared to the polymer isolated from broth culture equivalents. The clinical
      implications of these results are discussed in relation to the potential
      pathogenicity of P. cepacia in cystic fibrosis patients.

PMID- 7515964
TI  - Diagnostic and therapeutic potential of poly(benzyl L-glutamate).
AB  - Poly(benzyl L-glutamate) (PBLG) microcapsules, prepared by a solvent evaporation
      technique for intravenous injection, are evaluated for their potential use in
      diagnostic computed tomographic enhancement of liver images. The smaller
      microcapsules, < 3 microns, loaded with a radiopaque contrast material, ethyl
      iopanoate (IOPAE), produced prolonged opacification of the liver when delivered
      intravenously. In vivo tissue distribution studies of PBLG-131I-IOPAE (5
      microCi/rat, iv) showed that liver had the highest uptake (percent of injected
      dose/g of tissue) among other organs 24 h postinjection. An in vitro estrogen
      receptor assay in pig uteri indicated that PBLG conjugated with estrone did not
      interfere with estrogen receptor affinity, suggesting the estrogen therapy
      potential of PBLG-estrone.

PMID- 7515967
TI  - Ears for safe diving.

PMID- 7515965
TI  - Studies of a sperm/placenta cross-reacting antigen, STX-10.
AB  - A monoclonal antibody, HSA-10 initially produced against acrosome-reacted human
      sperm was also shown to cross-react with human placenta/trophoblast. Transmission
      electron microscopy, as well as indirect immunofluorescent assay, demonstrated
      that HSA-10 was found to react with antigen on the inner acrosome of human sperm.
      The cognate antigen, designated as STX-10, was found to exist as an aggregate in
      the native form when analyzed by Sephacryl S-300 gel filtration chromatography.
      When purified by HSA-10-immunoaffinity chromatography from human placenta
      extract, STX-10 was found to be predominantly a group of glycoproteins with a
      subunit molecular mass in the range of 75 +/- 5 kDa, whereas an additional group
      of three proteins with subunit molecular mass less than 20 kDa were copurified
      from human sperm extract. A sandwich enzyme immunoassay was designed to
      quantitatively determine the immunoactivity of STX-10 in solution, using HSA-10
      monoclonal antibody for coating and for signal detection via enzyme conjugation.
      Based on this assay, it was found that STX-10 could be detected only in human
      sperm and placenta extract, but not in any other human somatic tissues, such as
      serum, brain, heart, muscle, kidney and liver. The immunoactivity of STX-10 was
      found to be sensitive to proteolytic digestion, low pH, in the presence of
      reducing agent, but resistant to treatment with sodium periodate. This
      observation suggests that HSA-10 specific epitope is a peptide in nature and not
      a carbohydrate moiety. Results of antifertility studies revealed that HSA-10
      significantly inhibited human sperm penetration to zona-free hamster ova. Thus,
      the results of this study are consistent with those of WHO Workshop evaluations
      that seem to suggest that STX-10 is a highly gamete-specific antigen localized on
      the inner acrosome of human sperm and in human trophoblast/placenta. Therefore,
      it may play an important role during human fertilization and embryo development.

PMID- 7515966
TI  - Beethoven's illness: Whipple's disease rather than sarcoidosis?

PMID- 7515968
TI  - [Apoptosis in toxicology].

PMID- 7515969
TI  - The Cys-His motif of Ty3 NC can be contributed by Gag3 or Gag3-Pol3 polyproteins.
AB  - The major structural proteins capsid and nucleocapsid (NC) of the Saccharomyces
      cerevisiae retroviruslike element Ty3 are produced as domains within the Gag3 and
      Gag3-Pol3 precursor polyproteins. Ty3 NC contains one copy of the conserved motif
      CX2CX4HX4C found in most retroviral NC proteins. We show here that NC proteins
      derived by processing of these different precursor species differ at their
      carboxyl termini. To determine whether the Cys-His motifs of these nascent NC
      domains contribute differently to replication, Gag3 and Gag3-Pol3 fusion proteins
      containing wild-type or mutant Cys-His domains were expressed from separate
      constructs. Although the Cys-His box was shown to be essential for polyprotein
      processing of a wild-type Ty3 element, this domain could be contributed from Gag3
      or as part of Gag3-Pol3. These data suggest that the functions of the retroviral
      NC Cys-His domain contributed from Gag and Gag-Pol are redundant.

PMID- 7515970
TI  - High rates of frameshift mutations within homo-oligomeric runs during a single
      cycle of retroviral replication.
AB  - Homo-oligomeric runs were inserted into a spleen necrosis virus-based retrovirus
      vector to determine the nature and rate of mutations within runs of 10 to 12
      identical nucleotides during a single replication cycle. Clones of helper cells
      containing integrated copies of retroviral vectors were used to produce virus for
      infection of target (nonhelper) cells. Proviral sequences from target cell clones
      were compared with proviral sequences from helper cell clones to study mutations
      that occurred during a single cycle of replication. In addition to the internal
      region spanning the homo-oligomeric inserts, a naturally occurring run of 10 T's
      in the long terminal repeat (LTR) also was sequenced. Rates of mutation ranged
      from < 0.01 to 0.38 frameshift mutations per run per cycle for different
      nucleotide runs. Frameshift mutations ranged from deletions of 2 bases to
      additions of 5 bases; the most common mutations were +1 and -1. Frameshift
      mutation rates did not increase as the run length increased from 10 to 12 bases.
      Rates of frameshift mutation for runs of T's and A's were significantly higher
      than rates for runs of C's and G's, and rates for runs of pyrimidines were
      significantly higher than those for runs of purines. Interestingly, the vast
      majority of frameshift mutations in the internal region (95%) were positive,
      suggesting that the primer strand tends to slip backward on the template in this
      region. LTR runs had a significantly lower number of positive frameshift
      mutations than the internal runs. By analyzing the types of frameshift mutations
      within runs and by comparing the patterns of frameshift mutations in the 5' and
      3' LTRs of individual proviruses, we conclude that the majority of mutations
      observed in our system occurred during minus-strand DNA synthesis of reverse
      transcription.

PMID- 7515971
TI  - Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16
      transgenic mice.
AB  - To model human papillomavirus-induced neoplastic progression, expression of the
      early region of human papillomavirus type 16 (HPV16) was targeted to the basal
      cells of the squamous epithelium in transgenic mice, using a human keratin 14
      (K14) enhancer/promoter. Twenty-one transgenic founder mice were produced, and
      eight lines carrying either wild-type or mutant HPV16 early regions that did not
      express the E1 or E2 genes were established. As is characteristic of human
      cancers, the E6 and E7 genes remained intact in these mutants. The absence of E1
      or E2 function did not influence the severity of the phenotype that eventually
      developed in the transgenic mice. Hyperplasia, papillomatosis, and dysplasia
      appeared at multiple epidermal and squamous mucosal sites, including ear and
      truncal skin, face, snout and eyelids, and anus. The ears were the most
      consistently affected site, with pathology being present in all lines with 100%
      penetrance. This phenotype also progressed through discernible stages. An initial
      mild hyperplasia was followed by hyperplasia, which further progressed to
      dysplasia and papillomatosis. During histopathological progression, there was an
      incremental increase in cellular DNA synthesis, determined by 5-bromo-2'
      deoxyuridine incorporation, and a profound perturbation in keratinocyte terminal
      differentiation, as revealed by immunohistochemistry to K5, K14, and K10 and
      filaggrin. These K14-HPV16 transgenic mice present an opportunity to study the
      role of the HPV16 oncogenes in the neoplastic progression of squamous epithelium
      and provide a model with which to identify genetic and epigenetic factors
      necessary for carcinogenesis.

PMID- 7515972
TI  - Human immunodeficiency virus type 1 variants with increased replicative capacity
      develop during the asymptomatic stage before disease progression.
AB  - We examined the replicative properties of a series of sequential isolates and
      biological clones of human immunodeficiency virus type 1 (HIV-1) obtained from an
      individual who progressed from seroconversion to AIDS in approximately 5 years.
      HIV-1 isolated soon after seroconversion replicated slowly and to low levels in
      cultures of peripheral blood mononuclear cells; however, subsequent isolates
      obtained during asymptomatic infection showed a marked increase in replication
      kinetics. This was examined in more detail by using a panel of 35 biological
      clones of HIV-1 generated from sequential patient peripheral blood mononuclear
      cell samples. Each clone was evaluated for replication in primary macrophages and
      CD4+ T lymphocytes and for the ability to induce syncytium formation in MT-2 cell
      cultures. Consistent with earlier observations, we found that all of the clones
      isolated just after seroconversion were slowly replicating and non-syncytium
      inducing (NSI). However, NSI variants with increased replication kinetics in
      macrophages were identified soon thereafter. These variants preceded the
      appearance of NSI and syncytium-inducing variants, with rapid replication in both
      macrophages and CD4+ T lymphocytes. To determine whether changes in the rate of
      replication could be traced to the early stages of the virus life cycle, PCR
      assays were used to evaluate entry and reverse transcription of selected
      biological clones in macrophages and CD4+ T lymphocytes. We found there was no
      inherent block to entry or reverse transcription for the slowly replicating
      variants; however, this does not preclude the possibility that small differences
      in the rate of entry may account for larger differences in the replication
      kinetics over many cycles. Overall, our results demonstrate that rapidly
      replicating variants of HIV-1 emerge during the asymptomatic period in a patient
      who subsequently progressed clinically, suggesting that these variants may play
      an important role in HIV-1 pathogenesis.

PMID- 7515974
TI  - Unprocessed foot-and-mouth disease virus capsid precursor displays discontinuous
      epitopes involved in viral neutralization.
AB  - A foot-and-mouth disease virus (FMDV) cDNA cassette containing sequences encoding
      the capsid precursor P1, peptide 2A and a truncated 2B (abbreviated P1-2A) of
      type C FMDV, has been modified to generate the authentic amino terminus and the
      myristoylation signal. This construct has been used to produce a recombinant
      baculovirus (AcMM53) which, upon infection of Spodoptera frugiperda insect cells,
      expressed a recombinant P1-2A precursor with a high yield. This polyprotein
      reacted with neutralizing monoclonal antibodies (MAbs) that bind to continuous
      epitopes of the major antigenic site A (also termed site 1) of capsid protein
      VP1. Unexpectedly, it also reacted with neutralizing MAbs which define complex,
      discontinuous epitopes previously identified on FMDV particles. The reactivity of
      MAbs with P1-2A was quantitatively similar to their reactivity with intact virus
      and, in both cases, the reactivity with MAbs that recognized discontinuous
      epitopes was lost upon heat denaturation of the antigen. The finding that a
      capsid precursor may fold in such a way as to maintain discontinuous epitopes
      involved in virus neutralization present on the virion surface opens the
      possibility of using unprocessed capsid precursors as novel antiviral immunogens.

PMID- 7515973
TI  - Amino acid substitutions in the human immunodeficiency virus type 1 gp120 V3 loop
      that change viral tropism also alter physical and functional properties of the
      virion envelope.
AB  - The third variable (V3) region within the gp120 envelope glycoprotein of the
      human immunodeficiency virus type 1 (HIV-1) has been reported to be an important
      determinant of viral tropism. In this study a series of isogenic recombinant HIV
      1 viruses, containing V3 regions from fresh isolates, were examined to ascertain
      if a relationship exists between viral tropism and specific properties of the
      virion-associated envelope. All of the viruses were able to infect CD4+ primary
      lymphocytes, although with different infection kinetics. Several recombinants,
      however, were unable to infect a continuous CD4+ T-cell line permissive for the
      parental virus and exhibited a marked decrease in the kinetics of virion
      associated gp120 binding to a soluble form of CD4. A known macrophage-tropic HIV
      1 isolate, also unable to infect the T-cell line, bound CD4 with similarly slow
      reaction kinetics. Although the inability to infect T-cell lines is a commonly
      observed property of macrophage-tropic isolates of HIV-1, the loss of T-cell line
      tropism by the V3 recombinants was not accompanied by a substantial infectivity
      for monocyte-derived macrophages, as monitored by reverse transcriptase
      production. Additional analyses of the recombinant virion gp120s indicated that
      most of the V3 substitutions increased the inherent stability of the virion gp120
      gp41 envelope complex. These results indicate that V3-induced alterations in
      viral tropism are associated with changes in physical and functional properties
      of the virion envelope.

PMID- 7515976
TI  - Normal left ventricular diastolic compliance after regression of hypertrophy.
AB  - We wished to determine whether (a) left ventricular (LV) diastolic chamber
      compliance and tissue elastic modulus were decreased with hypertrophy and
      improved after reversal of hypertension and regression of hypertrophy and whether
      collagen concentration was a major determinant of LV chamber compliance during
      hypertrophy or aging. Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats
      (WKY), aged 8 months at time of study, were used for the hypertension-regression
      experiments. The aging study was based on 14- and 24-month-old Fischer-344 rats.
      LV chamber compliance was measured in isolated perfused hearts arrested in
      diastole. Length-tension curves (tissue elastic modulus) were obtained from
      ventricular strips, and hydroxyproline assays were used to estimate LV collagen
      content. Captopril and hydrochlorothizide were given for an 8-week period to both
      normotensive and hypertensive rats. Treatment normalized arterial pressure and
      caused regression of LV hypertrophy in SHR. LV diastolic compliance was less
      (pressure-volume curve steeper) in SHR than in WKY, but stiffness was similar in
      the two groups, as indicated by similar slopes when volume was adjusted for heart
      mass. Treatment significantly decreased ventricular stiffness in both SHR and
      WKY. Length-tension curves were almost identical in SHR and WKY, but treated SHR
      demonstrated less tension per given length. These changes occurred although
      collagen did not decrease in parallel to the decrease in LV mass. Aging was
      associated with 66 and 60% increases in collagen content and concentration,
      respectively, but did not alter LV chamber compliance significantly.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7515977
TI  - Pharmacologic profile of CGS 24128, a potent, long-acting inhibitor of neutral
      endopeptidase 24.11.
AB  - We compared the pharmacologic profiles of thiorphan, a neutral endopeptidase
      (NEP) inhibitor which is cleared rapidly from the circulation, and CGS 24128, an
      inhibitor with a much longer half-life (t1/2). Thiorphan and CGS 24128 inhibited
      NEP in vitro with IC50 values of 5.0 +/- 0.2 and 4.3 +/- 0.2 nM, respectively.
      After administration at 10 mg/kg intravenously (i.v.), the concentrations of CGS
      24128 in the plasma were > 500 nM for 4 h but plasma thiorphan was detectable for
      only 60 min. Thiorphan 3 mg/kg administered intraarterially (i.a.) increased
      plasma atrial natriuretic peptide immunoreactivity (ANPir) levels by 58 +/- 12%
      in rats administered exogenous ANP(99-126). This response lasted < 60 min,
      whereas the same dose of CGS 24128 produced an average increase of 191 +/- 19% in
      ANPir concentrations that persisted for 4 h. ANP-induced (1 microgram/kg i.v.)
      natriuresis was significantly potentiated in anesthetized rats pretreated (60
      min) with a bolus of CGS 24128 10 mg/kg i.v. The change in urinary sodium
      excretion (UNaV) produced by ANP was 28.8 +/- 4.0 and 15.8 +/- 1.8 muEq/kg/min in
      CGS 24128- and vehicle-treated rats, respectively. ANP-induced natriuresis was
      also greater during continuous infusion of thiorphan (5 mg/kg bolus + 0.1
      mg/kg/min i.v.; delta UNaV = 29.2 +/- 5.8 and 13.8 +/- 3.2 muEq/kg/min in drug-
      and vehicle-treated rats, respectively) but not when thiorphan was administered
      as a bolus (10 mg/kg i.v.) 60 min before the ANP challenge.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7515975
TI  - A novel, glycan-dependent epitope in the V2 domain of human immunodeficiency
      virus type 1 gp120 is recognized by a highly potent, neutralizing chimpanzee
      monoclonal antibody.
AB  - An anti-gp120 monoclonal antibody (MAb), C108G (gamma 1, kappa), was isolated
      from a chimpanzee that had been infected with strain IIIB of human
      immunodeficiency virus type 1 (HIV-1IIIB) and subsequently immunized with the
      recombinant glycoprotein rgp160MN. This MAb is specific for the IIIB strain of
      HIV-1 and related clones and exhibits very potent neutralization of these
      viruses; e.g., 100% neutralization of approximately 8 x 10(3) infectious units of
      HXB2 was achieved with 125 ng of C108G per ml. Commensurate with this potent
      neutralizing activity, the apparent affinity of C108G for rgp160LAI was very
      high, i.e., approximately 3 x 10(10) liters/mol. The C108G epitope was not
      destroyed by reduction of gp120 disulfide bonds but was profoundly disrupted by
      removal of N-linked sugars from gp120. Despite the importance of a glycan(s) in
      forming the C108G epitope, specific binding of C108G to synthetic peptides
      overlapping in amino acids 162 to 169 of the V2 region was detected, albeit with
      an affinity approximately 2,000-fold lower than that of C108G's binding to
      glycosylated envelope protein. This epitope mapping correlated with results of
      competition assays using MAbs of known epitope specificities. To our knowledge,
      this is the first description of an anti-V2 MAb raised in response to HIV-1
      infection. Its potent neutralizing activity and epitope specificity indicate that
      the V2 domain of gp120 may be an effective target of the protective immune
      response and, therefore, potentially an important component of HIV vaccines.

PMID- 7515978
TI  - Effects of preconditioning on reperfusion arrhythmias, myocardial functions,
      formation of free radicals, and ion shifts in isolated ischemic/reperfused rat
      hearts.
AB  - The effects of preconditioning on development of reperfusion-induced ventricular
      fibrillation (VF), ventricular tachycardia (VT), free radical formation, and ion
      shifts, particularly those of Na, K, Ca, and Mg, were studied in isolated rat
      heart. Hearts were randomly divided into four groups: group I, aerobically
      perfused time-matched controls with no preconditioning or ischemia; group II,
      hearts subjected to 30-min global ischemia followed by 30-min reperfusion; group
      III, hearts subjected to one cycle of preconditioning, consisting of 5-min global
      ischemia plus 10-min reperfusion, followed by 30-min global ischemia plus 30-min
      reperfusion; and group IV, hearts subjected to four cycles of preconditioning (5
      min ischemia plus 10-min reperfusion) followed by 30-min ischemia plus 30-min
      reperfusion. The incidences of VF and VT were reduced from their
      nonpreconditioned ischemic values of 100 and 100% in group II to 83 and 92% in
      group III and to 33% (p < 0.05) and 41% (p < 0.05) in group IV, respectively.
      Maximum malondialdehyde formation, as an indirect marker of free radicals, was
      observed after 30-min ischemia followed by 10-min reperfusion (0.72 +/- 0.1
      nmol/ml) in the nonpreconditioned ischemic group (protocol II). One and four
      cycles of preconditioning reduced formation of malondialdehyde from the
      nonpreconditioned ischemic value of 0.72 +/- 0.1 to 0.35 +/- 0.02 and 0.26 +/-
      0.02 nmol/ml (p < 0.05), respectively. The same trend was observed when free
      radical formation was directly detected by salicylic acid.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7515979
TI  - Electrophysiologic effects of intravenous E-4031, a novel class III
      antiarrhythmic agent, in patients with supraventricular tachyarrhythmias.
AB  - The electrophysiologic effects of intravenous (i.v.) E-4031, a new class III
      antiarrhythmic drug, were evaluated in 15 patients with supraventricular
      tachyarrhythmias [11 men, 4 women; mean age 41 +/- 19 (SD) years]. Eleven
      patients had accessory atrioventricular (AV) pathways, and 4 patients with no
      accessory pathway had paroxysmal atrial fibrillation. Electrophysiologic studies
      were performed before and after E-4031 administration (loading infusion 9
      micrograms/kg for 5 min + maintenance infusion 0.15 microgram/kg/min). QT and QTc
      intervals were significantly prolonged by E-4031 from 0.40 +/- 0.03 (mean +/- SD)
      to 0.46 +/- 0.03 s (p < 0.0001) and from 0.43 +/- 0.03 to 0.49 +/- 0.04 s (p <
      0.0001), respectively. No effect was observed on RR interval, PR interval, QRS
      duration, or AH and HV intervals. The effective refractory periods (ERPs) of the
      right atrium and ventricle were significantly prolonged from 219 +/- 27 to 236 +/
      26 ms (p < 0.001) and from 230 +/- 12 to 249 +/- 11 ms (p < 0.001),
      respectively. The ERP of the AV node did not change significantly after E-4031
      administration. In patients with ventricular preexcitation, E-4031 significantly
      prolonged the ERP of the antegrade accessory pathway conduction from 340 +/- 101
      to 362 +/- 106 ms (p < 0.001), but not retrograde accessory pathway conduction.
      AV reentrant tachycardia was induced in 3 of 11 patients with an accessory
      pathway, and repetitive atrial firing was induced in 3 of 4 patients with
      paroxysmal atrial fibrillation. E-4031 could prevent repetitive atrial firing in
      only 1 patient and could not prevent induction of AV reentrant
      tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515983
TI  - Inhibitory effect of trimetazidine on thrombin-induced aggregation and calcium
      entry into human platelets.
AB  - The antiaggregatory properties of trimetazidine were investigated further by
      analyzing its effects on cytosolic calcium and proton concentrations, well-known
      regulators of platelet reactivity. Aggregatory responses of washed platelets were
      assessed by turbidometry, and cytosolic Ca2+ concentration ([Ca2+]i) and pH (pHi)
      were determined by their respective fluorescent probes: Fura-2 and BCECF.
      Preincubation with trimetazidine dose-dependently inhibited platelet aggregation
      induced by 0.05 U/ml thrombin (p < 0.001). At concentrations < or = 1 mM,
      trimetazidine did not affect the resting [Ca2+]i value but slightly alkalinized
      the cytosol by 0.05 +/- 0.03 pH units (p < 0.02, n = 11). In platelets stimulated
      by 0.05 U/ml thrombin, 0.1 mM trimetazidine did not modify pHi variations but
      decreased [Ca2+]i variations (p < 0.003, n = 16), blunting by 28 +/- 6% the
      transient peak of [Ca2+]i (p < 0.006) and decreasing by 6 +/- 2% the equilibrium
      value (p < 0.005). These inhibitory effects were inversely dependent on thrombin
      concentrations (p < 0.004, n = 21) and were abolished in the virtual absence of
      external Ca2+. Trimetazidine therefore attenuates the Ca2+ influx evoked by
      thrombin, thereby limiting Ca2+ accumulation in stimulated platelets. Such a
      protective effect may participate in the antiaggregatory properties of
      trimetazidine.

PMID- 7515982
TI  - Involvement of calcium channels in fibroblast growth factor-induced activation of
      arterial cells in spontaneously hypertensive rats.
AB  - To gain insight into the mechanisms that could account for the abnormal vascular
      structure in spontaneously hypertensive rats (SHR) and to determine whether this
      could be affected by calcium channel blockers, we compared the influence of
      dihydropyridines on basic fibroblast growth factor (bFGF)-induced DNA synthesis
      in cultured adventitial fibroblasts isolated from SHR and Wistar-Kyoto rat (WKY)
      aorta. Our results showed that (a) bFGF was a potent mitogen for adventitial
      fibroblasts, much more active in SHR-derived than in WKY-derived cells, thus
      confirming the hyperreactivity of the SHR arterial cells; (b) the mitogenic
      potency of bFGF could be reduced by dihydropyridines (rank order of potency was
      nifedipine approximately nisoldipine > nitrendipine > nimodipine); and (c) the
      nifedipine inhibitory effect could be completely and partially antagonized in WKY
      and SHR-derived fibroblasts, respectively, by the calcium channel agonist Bay K
      8644. Moreover, the extent of nifedipine inhibitory extent increased and
      decreased in SHR- and WKY-derived fibroblasts, respectively, according to
      duration of treatment of cells with the drug, suggesting that SHR fibroblasts
      became progressively more sensitive whereas those of WKY became more refractory
      to the drug treatment. These data indicate that in aortic fibroblasts stimulated
      by bFGF, L-type calcium channels participate in the antimitotic effect of
      dihydropyridines and suggest the existence of interactions between these channels
      and the bFGF signaling pathways. They also suggest that nifedipine inhibits bFGF
      induced DNA synthesis by different mechanisms in SHR and WKY fibroblasts.

PMID- 7515980
TI  - Antiischemic effects of nifedipine in isolated working heart preparations of
      healthy, diabetic, and hypertensive rats.
AB  - We evaluated the antiischemic effects of nifedipine in isolated working rat
      hearts from age-matched normotensive Wistar-Kyoto rats (WKY), diabetic WKY,
      spontaneously hypertensive rats (SHR), and diabetic SHR. Diabetes was induced by
      streptozotocin. First, we constructed concentration-response curves for the
      negative inotropic effect of nifedipine in every group. After 15 min of
      pretreatment with nifedipine (EC60), low-flow ischemia (30 min) was induced by
      reducing the afterload from 51.5 to 11.0 mm Hg and nifedipine was infused
      simultaneously. The six measured parameters were left ventricular pressure (LVP),
      maximum rate of pressure increase (+dP/dtmax), maximum rate of pressure decrease
      (-dP/dtmax), aortic output (AO), coronary flow (CF), and cardiac output (CO),
      determined after 15-min equilibration in the working heart mode and at the end of
      the experiment. From these data, the recovery percentages were calculated. There
      were no significant differences in sensitivity to nifedipine (as measured by the
      EC50 concentration) between the four groups with respect to LVP, +dP/dtmax, 
      dP/dtmax, CF, and CO. However, hearts from SHR were less sensitive to nifedipine
      than those from diabetic SHR and nondiabetic WKY with regard to AO. In isolated
      hearts from nondiabetic WKY and SHR, there were no significant differences
      between vehicle-treated organs and nifedipine-treated preparations. In hearts
      from diabetic WKY and diabetic SHR, however, the nifedipine-treated group (LVP
      87.1 +/- 3.3 and 60.5 +/- 12.1%, respectively) recovered significantly (p < 0.05)
      better from ischemia as compared with the control group (LVP 35.7 +/- 14.7 and
      10.7 +/- 9.8%, respectively) (n = 6 for each group).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7515981
TI  - Platelets increase the tone of quiescent rat aortic rings by release of serotonin
      and potentiate the subsequent contractile response to norepinephrine.
AB  - To examine the effect of platelets on the tone of quiescent vessels, rat aortic
      rings with intact endothelium and others with denuded endothelium were exposed to
      platelets in an organ bath. Suspension of washed platelets induced a mild but
      consistent contraction of rings with intact endothelium. The subsequent
      contractile response of these rings to norepinephrine (NE) was also potentiated.
      Platelets caused a marked contraction of quiescent rings without intact
      endothelium and potentiated the subsequent contractile effects of NE. The
      procontractile effect of platelets in rat aortic rings with and without intact
      endothelium was not modulated by the selective thromboxane A2 (TXA2)/endoperoxide
      receptor antagonist SQ29,548 or the cyclooxygenase inhibitor indomethacin, but
      was completely blocked by serotonin (S2) receptor antagonist LY53,857, suggesting
      that release of serotonin from aggregating platelets is perhaps more important
      than release of TXA2 in the procontractile effects of platelets on quiescent rat
      aortic rings. To examine the role of vascular endothelium in the procontractile
      effect of platelets further, we treated aortic rings with intact endothelium with
      the inhibitor of endothelium-derived relaxing factor (EDRF) NG-monomethyl-L
      arginine (L-NMMA) or the adenine nucleotide scavenger apyrase. In rings treated
      with L-NMMA or apyrase, the contractile effect of platelets was enhanced (p <
      0.01) and mimicked that in rings without intact endothelium. These observations
      indicate that although basal release of EDRF modulates the contractile effect of
      platelets, the dominant effect of platelets on quiescent rat aortic rings with
      intact endothelium is procontractile and this effect is mediated exclusively by
      release of serotonin.

PMID- 7515984
TI  - Hemodynamic effects of the new antiarrhythmic agent restacorin in patients with
      normal and decreased left ventricular function.
AB  - The hemodynamic and pharmacokinetic effects of the novel class 1c antiarrhythmic
      drug restacorin were investigated in two groups of patients. Group I consisted of
      5 patients with normal left ventricular (LV) function, and group II consisted of
      10 patients with mild heart failure [New York Heart Association (NYHA) II; mean
      LV ejection fraction 33 +/- 6%]. The study had an open label, baseline
      controlled, single-dose design. Restacorin was infused in a total dosage of 1.2
      mg/kg. In group I, the only significant change as compared with baseline findings
      was a 25% increase in right atrial pressure. In group II; cardiac output (CO),
      dP/dt, and stroke work index (SWI) decreased significantly (-18, -11, and -24%,
      respectively). In addition, a significant 32% increase was noted in pulmonary
      artery wedge pressure (PAWP), and a 27% increase occurred in systemic vascular
      resistance (SVR). No changes were observed in heart rate (HR) or mean arterial
      blood pressure (MAP). CO and SVR at baseline correlated with the average plasma
      concentrations (r = -0.65 and p = 0.009 and r = 0.56 and p = 0.028 respectively).
      Creatinine clearance was inversely correlated to the restacorin plasma
      concentration (r = -0.51, p = 0.05). The half-life (t1/2) elimination time of
      restacorin was 2.60 h for group I, and 4.06 h for group II. Clearance was 51.4
      and 32.2 L.h-1, respectively. Restacorin appears to be well tolerated in patients
      with normal LV function. The drug is not recommended for use in patients with
      reduced LV function because of its moderate negative inotropic effect.

PMID- 7515985
TI  - Comparison of the antiatherogenic effects of isradipine and ramipril in
      cholesterol-fed rabbits: I. Effect on progression of atherosclerosis and
      endothelial dysfunction.
AB  - This study was designed to compare the effects of a calcium antagonist
      (isradipine) and a converting enzyme inhibitor (ramipril) on progression and
      regression of atherosclerosis in hypercholesterolemic rabbits. Sixty rabbits in
      three groups were fed a 0.3% cholesterol diet for 4 weeks. After this induction
      period, group II received the 0.3% cholesterol diet, group III received
      cholesterol diet with isradipine (0.33 mg/kg/day), and group IV received
      cholesterol with ramipril (0.33 mg/kg/day) for 12 more weeks. A group of 20
      rabbits received a standard diet throughout the study (group I). After 16 weeks,
      10 rabbits were randomly chosen from each group and used in the progression
      study. The other rabbits were placed on a standard diet and remained on their
      respective drug regimen for 12 more weeks. In the progression phase of the study,
      ramipril significantly attenuated the percentage of aortic lesions in group IV
      (35 +/- 6%) as compared with group II (56 +/- 6%, p < 0.05), whereas isradipine
      had no effect. Acetylcholine (ACh)-induced maximum endothelium-dependent
      relaxations (EDR) of aortic rings were significantly reduced by the atherogenic
      diet to 37 +/- 4 versus 77 +/- 2% in group I (p < 0.05). Treatment with ramipril
      significantly improved maximum EDR to 53 +/- 3% (p < 0.05 vs. group II).
      Isradipine had no significant effect on impaired EDR. Aortic rings with
      endothelium from group II developed supersensitivity to sodium nitroprusside
      (SNP) and had significantly reduced basal cyclic GMP levels as compared with
      those of group I. Both drugs prevented development of supersensitivity to SNP and
      blunted the cholesterol-induced reduction in basal cyclic GMP levels.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7515986
TI  - Comparison of the antiatherogenic effects of isradipine and ramipril in
      cholesterol-fed rabbits: II. Effect on regression of atherosclerosis and
      restoration of endothelial function.
AB  - We report the effects of isradipine and ramipril on regression of diet-induced
      atherosclerosis in rabbits. Regression of diet-induced atherosclerosis was not
      significantly affected by ramipril, but isradipine significantly retarded
      regression. Thirty rabbits in three groups were fed a 0.3% cholesterol diet for 4
      weeks. After this induction period, group IIr received the 0.3% cholesterol diet,
      group IIIr received the 0.3% cholesterol diet with isradipine (0.33 mg/kg/day),
      and group IVr received the 0.3% cholesterol diet with ramipril (0.33 mg/kg/day)
      for 12 more weeks. The rabbits then received a standard diet and remained on
      their respective drug regimen for 12 more weeks. Group Ir (10 rabbits) received a
      standard diet for 28 weeks. Acetylcholine (ACh)-induced maximal endothelium
      dependent relaxations (EDR) of aortic rings were significantly less in group IIr
      (22.8 +/- 3.2%) than in group Ir (66.4 +/- 4.0%; p < 0.05). Ramipril and
      isradipine did not improve EDR as compared with group IIr. Regression of
      atherosclerosis was accompanied by an improved endothelium-dependent releasing
      factor (EDRF) release from the endothelium, but ramipril and isradipine did not
      promote this process. In addition, regression was associated with increasing
      sensitivity of vascular smooth muscle to EDRF that was significantly retarded by
      isradipine but not ramipril. Basal cyclic GMP levels were significantly reduced
      in aortic rings from group IIr as compared with group Ir. Ramipril, but not
      isradipine, restored basal cyclic GMP levels to control values. Both isradipine
      and ramipril protect against endothelial degeneration in hypercholesterolemic
      rabbits. However, isradipine but not ramipril inhibits regression of diet-induced
      atherosclerosis in rabbits.

PMID- 7515987
TI  - Effects of aging and hypertension on vasorelaxant activity of calcitonin gene
      related peptide: a comparison with other vasodilator agents.
AB  - We investigated the influence of aging and hypertension on the vasorelaxant
      effect of calcitonin gene-related peptide (CGRP), examining the responses to
      stimulation of perivascular vasodilatory nerves and to administration of the
      peptide in isolated mesenteric vascular bed preparations of young (aged 2-3
      months) and old (aged 18 months) normotensive Wistar-Kyoto (WKY) rats and
      spontaneously hypertensive rats (SHR). We used preparations preconstricted by
      perfusion with 100 microM methoxamine with addition of 5 microM guanethidine. The
      stimulation-induced vasorelaxation in the preparations of young SHR animals was
      significantly lower than that in those of age-matched WKY rats. Moreover, the
      vasodilator response to stimulation displayed an age-dependent decline in
      vascular beds of normotensive animals. The degree of the relaxant response to
      CGRP (0.01-1 microM) did not differ significantly between vascular preparations
      of normotensive and hypertensive rats; but was significantly reduced in
      preparations of both SHR and WKY rats aged 18 months as compared with those of
      young animals. An age-dependent decrement in the vascular reactivity,
      qualitatively similar to that observed with CGRP, was also detected with two
      other vasodilators, i.e., the endothelium-dependent vasodilator acetylcholine
      (ACh 0.1-100 microM) and the directly acting nitrovasodilator sodium
      nitroprusside (SNP, 1-10 microM). We conclude that the vascular sensitivity to
      CGRP, as well as that to other vasodilator agents acting by different mechanisms,
      decreases with age in both normotensive and genetically hypertensive rats.

PMID- 7515988
TI  - Modulation of norepinephrine release in adriamycin-induced heart failure in
      rabbits: role of presynaptic alpha 2-adrenoceptors and presynaptic angiotensin II
      receptors.
AB  - In congestive heart failure (CHF), sympathetic neurotransmitter release is
      enhanced. We investigated the possibility that this is due in part to alterations
      in activation of either release-inhibiting alpha 2-adrenoceptors or release
      enhancing angiotensin II (AII) receptors at postganglionic sympathetic nerve
      endings. CHF was induced in rabbits by adriamycin [1 mg/kg intravenously (i.v.),
      twice weekly for 8 weeks] and was characterized by reduced cardiac output (CO)
      and enhanced norepinephrine (NE) release rate in pentobarbital-anesthetized
      rabbits. After pithing and stimulation of the spinal sympathetic outflow, there
      was no difference in NE release rate between the two groups, suggesting that the
      enhanced NE release rate observed in adriamycin-treated anesthetized rabbits was
      of central origin. The alpha 2-adrenoceptor-blocking drug yohimbine (1 mg/kg,
      i.v.) enhanced NE release rate, which is an indication of feedback inhibition of
      NE release through presynaptic alpha 2-adrenoceptors. In anesthetized rabbits,
      this effect of yohimbine was greater in adriamycin-treated than in vehicle
      treated animals. However, in pithed rabbits with electrically stimulated
      sympathetic outflow, there was no difference in the facilitative effect of
      yohimbine between the two groups, suggesting that inhibitory presynaptic alpha 2
      adrenoceptors are activated to a greater extent in heart failure due to the
      increased transmitter release. Removing inhibitory alpha 2-adrenoceptor input has
      a functional consequence in that yohimbine increased heart rate (HR) in
      adriamycin-treated but not in vehicle-treated anesthetized rabbits. Captopril (1
      mg/kg, i.v.) decreased NE release rate in pithed rabbits with stimulated
      sympathetic outflow but had no effect on NE release rate in anesthetized
      rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7515989
TI  - Effects of intracoronary glyburide on cesium-induced arrhythmias in anesthetized
      dogs.
AB  - Intracellular calcium plays an essential role in regulation of many cellular
      processes, but increases in internal calcium levels can also exacerbate
      pathophysiologic or pharmacologic responses, in particular myocardial
      arrhythmias. Pharmacologic increases in intracellular calcium may be obtained by
      opening calcium channels, either directly or indirectly, or by increasing calcium
      release from intracellular stores. In this study, cesium chloride administered
      intracoronarily (i.c.) through the left anterior descending coronary artery (LAD)
      dose-dependently elicited ventricular arrhythmias. Glyburide (3 micrograms/kg/min
      i.c.), clofilium (1 micrograms/kg/min i.c.) or ryanodine (0.03 micrograms/kg/min
      i.c.) exacerbated arrhythmias. Specifically, the ED50 values for cesium were
      shifted from 0.56 mM in the vehicle group to 0.17, 0.27, and 0.20 mM in the
      glyburide, clofilium, and ryanodine groups, respectively. Coronary blood flow
      (CBF) and blood pressure (BP) did not change significantly in any treatment
      group. Effects of glyburide were not mediated by either insulin or decreased
      glucose levels, since infusions of insulin (decreasing blood glucose to 20 mg/dl)
      did not exacerbate arrhythmias. In vitro electrophysiologic studies showed that
      glyburide (1 microM) and ryanodine (1 microM) did not significantly affect action
      potential durations (APD). In contrast, clofilium (1 microM) significantly
      prolonged APD. These results demonstrate that glyburide, clofilium, and ryanodine
      tend to exacerbate cesium-induced arrhythmias. We suggest that glyburide and
      ryanodine may exacerbate arrhythmias by increasing internal calcium from
      intracellular stores, whereas clofilium may increase internal calcium by
      increasing influx of calcium across the sarcolemma.

PMID- 7515990
TI  - Cooling augments human saphenous vein reactivity to electrical stimulation.
AB  - Human saphenous veins were obtained at operation and assayed immediately (n =
      10). The veins were cut into rings, suspended in organ chambers, and connected to
      force transducers for recording of isometric tension. One ring served as control;
      others were treated with either the alpha 1-adrenoceptor antagonist prazosin (Pz,
      3 x 10(-7) M) or the alpha 2-adrenoceptor antagonist rauwolscine (Rw1, 10(-7) M).
      Cooling from 37 degrees to 24 degrees C had no significant effect on the resting
      tone of quiescent rings. Electrical stimulation (0.2-16 Hz) caused frequency
      dependent contractions in control vessels. The contractions were inhibited by Pz
      (p < 0.001) and by Rw (p < 0.001). In control rings, cooling potentiated
      contractions evoked at all frequencies. Similar augmentations were induced by
      cooling in rings treated with the alpha 1-antagonist Pz. In contrast, rings
      treated with Rw before being electrically stimulated showed no significant change
      in contractile force when cooled. The data indicate that in the human saphenous
      vein, both alpha 1- and alpha 2-adrenoceptors are innervated, contributing to
      contractile response evoked by neuronal excitation. Cold augments saphenous vein
      reactivity to endogenously released norepinephrine (NE) by an apparent increase
      in the responsiveness of alpha 2-adrenoceptors to agonists. This relationship
      between temperature and adrenoceptor responsiveness is consistent with the
      hypothesized role of alpha 2-adrenoceptors in cold-induced vasospasm.

PMID- 7515991
TI  - Long-term systemic hemodynamic effects of cotinine in rats.
AB  - Cigarette smoking has been epidemiologically correlated with lower BP in humans,
      despite the acute BP effects of nicotine. Cotinine, a primary metabolite of
      nicotine, has been suggested as a mediator of the BP-lowering effect of smoking.
      To determine the cardiovascular effects of cotinine itself, arterial BP was
      monitored continuously in chronically instrumented Sprague-Dawley rats before,
      during, and after 14 days of intraarterial (i.a.) infusion of cotinine or
      placebo. Cardiovascular data were collected and analyzed by microcomputer for
      diurnal changes and for light- and dark-cycle averages. Heart rate (HR) was
      higher in both precotinine and placebo groups during the dark cycle than during
      the light cycle. HR was significantly lower (p < 0.025) during cotinine infusion
      in the cotinine group as compared with placebo. Five days after cotinine
      infusion, however, HR was not different from that of placebo controls. Arterial
      BP was not different between cotinine- and placebo-treated rats at any time
      period. The difference between HR but not arterial BP suggested that baroreceptor
      activity might differ after cotinine administration. Baroreceptor activity,
      assessed by analysis of HR changes evoked by phenylephrine, did not differ before
      and during cotinine administration, however. We conclude that cotinine did not
      decrease BP in rats under the present experimental conditions, but that cotinine
      was probably responsible for the observed bradycardia.

PMID- 7515992
TI  - Pharmacokinetics of amlodipine and its occupancy of calcium antagonist receptors.
AB  - We characterized the occupancy of dihydropyridine (DHP) calcium antagonist
      receptors by amlodipine in spontaneously hypertensive rats (SHR) in relation to
      its pharmacokinetics. Oral administration of amlodipine (10 mg/kg) in SHR
      produced a significant (20-70%) decrease in the number of specific (+)[3H]PN 200
      110 binding sites in cardiac tissues 0.5-18 h later, and the effect was greatest
      3 h later. In these rats, there was little change in cerebral cortical (+)[3H]PN
      200-110 binding. Occupancy of cardiac calcium antagonist receptors after oral
      administration of amlodipine correlated well with its plasma concentration. In
      vitro blockade of cardiac (+)[3H]PN 200-110 binding sites induced by amlodipine
      also persisted after the tissues were washed by centrifugation and suspension,
      whereas that induced by nifedipine was reversible under these conditions. Thus,
      our results suggest that the gradual onset and long-lasting pharmacologic effect
      of amlodipine are due to its slow binding kinetics (association and dissociation)
      of cardiovascular receptor sites in addition to its slow pharmacokinetics.

PMID- 7515994
TI  - Renal protective effects of amlodipine on partially nephrectomized spontaneously
      hypertensive rats fed a high-salt diet.
AB  - We examined the effects of a calcium-channel blocker amlodipine on progression of
      renal failure in 5 of 6 nephrectomized spontaneously hypertensive rats (SHR) fed
      a high-salt diet. Twelve SHR, 5 of 6 with nephrectomy and salt-loading, were
      divided into two group: group 1 as control (n = 6) and group 2 treated with 2
      mg/kg/day amlodipine (n = 6). During the 10 study weeks, body weight, systolic
      blood pressure (SBP), and daily urinary protein excretion were measured every 2
      weeks. At the end of the study, serum creatinine, urea nitrogen, and total
      protein and albumin were determined. Renal tissues were obtained for light
      microscopic examination. The increase in SBP after 10 study weeks was
      significantly less in the treated group than in the control group (control 287 +/
      5 mm Hg; amlodipine 237 +/- 23 mm Hg (p < 0.01)). Urinary protein excretion was
      also suppressed in the amlodipine-treated group (p < 0.01). Although in the
      control group glomerular sclerosis and hyalinosis were marked, they were
      significantly less in the amlodipine-treated group. These results illustrate that
      amlodipine can attenuate BP increase and inhibit progression of hypertensive
      renal injury in this rat model.

PMID- 7515993
TI  - Glibenclamide-induced oscillation of canine coronary artery is independent of
      myocardial ischemia.
AB  - To investigate the in vivo role of the ATP-sensitive potassium channel (KATP) in
      the coronary arteries, we examined the effects of intravenous (i.v.)
      glibenclamide (GLB, 0.3, 1.0, and 3.0 mg/kg), a specific KATP blocker, in
      chronically instrumented dogs. Epicardial coronary artery diameter (CoD) and
      coronary blood flow (CBF) were measured continuously. CoD and CBF oscillated in
      all 6 dogs after injection of 3 mg/kg GLB. CoD oscillated only slightly, with a
      decrease of 2.3 +/- 0.4%; CBF showed marked oscillation, with a peak flow rate of
      21.9 +/- 2.7 ml/min (+26.6%) and a trough flow rate of 10.3 +/- 2.9 ml/min (
      46.3%) (baseline flow rate was 17.8 +/- 2.4 ml/min). GLB 1 mg/kg produced a
      slight decrease in CBF without oscillation, and at 0.3 mg/kg had almost no
      effect. These oscillations were not associated with a decrease in myocardial
      blood flow as measured by the hydrogen gas clerance method. Nicorandil (0.2
      mg/kg), cromakalim (20 micrograms/kg), and diltiazem (0.2 mg/kg) almost
      completely suppressed the GLB-induced oscillations, but nitroglycerin (NTG 15
      micrograms/kg) did not. Thus, oscillation of large and small coronary arteries
      was induced by GLB and was independent of myocardial ischemia. In addition, these
      findings suggest that KATP has an important in vivo role in modulating large and
      small coronary artery tone through activation of the voltage-dependent Ca2+
      channel.

PMID- 7515995
TI  - Integrative cardiovascular actions of a novel catecholamine, GP-2-128.
AB  - Systematic modification in the chemical structure of dobutamine resulted in
      production of a long-acting, highly potent catecholamine, GP-2-128 [(1-(3,4
      dihydroxyphenyl)-2-[3-(4-carbamyl phenyl)-1-methylpropylamino] ethanol)]. The
      cardiovascular actions of GP-2-128 were compared with those of isoproterenol
      (ISO) and dobutamine (DOB) in anesthetized dogs. GP-2-128 significantly increased
      left ventricular pressure (LVdP/dtmax), cardiac output (CO), and heart rate (HR).
      It also reduced total peripheral vascular resistance (TPVR). For a given increase
      in contractility, changes in HR were greater after ISO than after GP-2-128
      administration. DOB did not change HR significantly. Both GP-2-128 and DOB
      reduced TPVR, but ISO was more effective than GP-2-128 and DOB in reducing TPVR.
      GP-2-128 was 18,000 and 52 times more potent than DOB and ISO, respectively, in
      increasing LVdP/dtmax. For a given increase in contractility, the cardiovascular
      actions of GP-2-128 lasted significantly longer than those of DOB or ISO. A 50%
      mixture of the RR and RS distereoisomer forms of GP-2-128 (GP-2-114) have the
      same pharmacologic profile as the pure RR distereoisomer. Both GP-2-128 and GP-2
      114 produced current-dependent cardiovascular actions when administered by
      transdermal iontophoresis. The inotropic and chronotropic effects of GP-2-128 are
      both largely due to stimulation of beta-adrenoceptors, as shown by receptor
      blockade with propranolol. GP-2-128 is a very potent, long-acting catecholamine
      that can be administered by other than intravenous (i.v.) route.

PMID- 7515998
TI  - Time course of direct cardiotoxic effects of high cocaine concentration in
      isolated rabbit heart.
AB  - Studies of acute cocaine cardiotoxicity are often confounded by the effects of
      cocaine on peripheral hemodynamics and an intact sympathetic nervous system. To
      study the direct effects of an acute dose of cocaine on heart, we used
      Langendorff-perfused isolated rabbit hearts. The hearts were attached to a
      Langendorff perfusion system through the aorta and were perfused with Krebs
      Henseleit buffer. In nonpaced hearts, cocaine in concentrations of 10, 25, and 50
      microM (reported to be in the range of drug concentrations lethal for humans)
      caused dose-dependent deterioration in heart contractility (decrease in +dP/dt, 
      dP/dt, and developed pressure) and coronary flow, when measured at 10, 20, and 30
      min of the protocol. Cocaine 25 and 50 microM also caused a decrease in heart
      rate (HR). In paced hearts treated with cocaine 50 microM, early events included
      a progressive decrease in +dP/dt (by 15% vs. baseline at 20 s of perfusion and by
      26% vs. baseline and 19% vs. control group at 30 s of perfusion; p < 0.05) and in
      -dP/dt (by 20% vs. baseline at 30 s of perfusion and by 25% vs. baseline and 15%
      vs. control group at 40 s of perfusion, p < 0.05). Decrease in HR (failure to
      pace) was observed only at 60 s of perfusion and averaged 20% versus both
      baseline and control group (p < 0.05). No changes in coronary flow were observed
      during the first 60 s after onset of cocaine administration.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7515997
TI  - Combination ethacizin and ethmozin treatment of resistant ventricular ectopy:
      theoretical, experimental, and clinical study.
AB  - Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with
      different rate constants of interaction with the sodium channel. Computer
      simulation using the "guarded-receptor" model predicted that the combination of
      ethacizin and ethmozin should exert a greater decrease in excitability and
      conduction at short coupling intervals, but little effect at normal heart rates
      (HR). To test this prediction, we measured intraventricular conduction delay in
      canine hearts in vivo. In agreement with the model, the combination more potently
      prolonged the delay only at intervals < 600 ms as compared with ethacizin alone.
      Combination therapy was tested in 6 patients with idiopathic ventricular ectopic
      depolarizations (VEDs). Three patients were resistant to either ethmozin or
      ethacizin monotherapy, and three could not tolerate effective doses because of
      side effects. Quantitative continuous ECG monitoring showed that total VEDs in
      the resistant group decreased 0 and 17 +/- 13% for 400 and 800 mg/day ethmozin
      and 18 +/- 12 and 55 +/- 12% for 100 and 200 mg/day ethacizin, respectively.
      Combined therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced
      the number of VEDs by 78 +/- 2% in these patients without side effects. In the
      "nonresistant" but intolerant group of patients, use of the combination allowed
      relief of symptomatic ectopy without side effects. A theoretical model correctly
      predicted an effective combination of class I antiarrhythmic drugs, one with
      "fast-off" and one with "slow-off" kinetics, which may provide a general
      rationale for choosing drug combinations.

PMID- 7515996
TI  - Interactions of a novel catecholamine, GP-2-128, with adrenoceptors.
AB  - GP-2-128 is a novel catecholamine designed for transdermal iontophoretic delivery
      in patients with limited mobility to prevent deconditioning and muscular wasting.
      We characterized the interactions of this agent with alpha- and beta
      adrenoceptors in vitro. In electrically stimulated rat left atria, GP-2-128
      produced a concentration-dependent increase in contractile force. pD2 values for
      GP-2-128, isoproterenol (ISO), and dobutamine (DOB) were 10.6 +/- 0.12, 8.55 +/-
      0.02, and 7.0 +/- 0.20, respectively. Metoprolol caused a shift in the
      concentration-effect curves for the three agonists. In spontaneously beating rat
      right atria, pD2 values of GP-2-128, ISO, and DOB are 10.4 +/- 0.24, 8.82 +/-
      0.18, and 6.92 +/- 0.18, respectively. The affinity constant (KA) of GP-2-128,
      ISO, and DOB for cardiac beta 1-adrenoceptors was determined by competition
      binding assays to be 8.09, 6.04 and 4.49, respectively. In guinea pig trachea
      precontracted with histamine, GP-2-128 and ISO produced a concentration-dependent
      relaxation. pD2 values were 10.0 +/- 0.1 and 8.2 +/- 0.1, respectively. DOB was
      more potent than GP-2-128 in contracting isolated rat aortic rings (alpha 1
      effect) and in displacing [3H]rauwolscine (alpha 2 effect). We also studied the
      interactions of GP-2-128 and ISO with the atypical beta-adrenoceptors (beta 3) in
      guinea pig ilea and rat and hamster adipocytes. Both agents inhibited twitches
      produced by transmural nerve stimulation in the presence of 10(-5) M nadolol. The
      EC30 for GP-2-128 and ISO at this atypical receptor site were 4.25 x 10(-10) and
      5.05 x 10(-8) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516000
TI  - Plasma erythrocyte relationship of catecholamines in human blood.
AB  - The equilibrating process of catecholamines (CAs) between plasma and red blood
      cells (RBC) was studied by measuring their erythrocyte/plasma concentration
      gradient (E/P ratio); ratio of E/P > 1 for a given amine was considered the
      consequence of its accumulation in or on RBC. We studied in vitro human blood
      obtained from 9 polycythemic patients from whom blood was drawn in control
      condition and in response to loading with exogenous CAs. Preliminary study showed
      a lack of difference in results obtained in these patients from those in 9
      healthy volunteers and confirmed that RBC accumulate dopamine (DA) and
      epinephrine (EPI) but not norepinephrine (NE). When a moderate amount of
      exogenous CAs was added, plasma and RBC concentrations were increased, with a
      delay between the two compartments indicated by a decrease in the E/P ratio of DA
      and EPI. When a large amount of exogenous CAs was added, their RBC concentrations
      were in direct proportion to their plasma concentrations. Thus, the kinetics of
      CA equilibration between plasma and RBC appears to be dependent on their chemical
      structure (DA is more easily accumulated than NE) and their plasma
      concentrations. Physiologically, the E/P ratio of DA was significantly greater
      than 1, suggesting that RBC maintained their capacity to accumulate DA even when
      DA plasma concentration was very high. Additional studies demonstrated that
      accumulation of CAs in or on RBC is a reversible process, inhibited by cold
      temperature and increased when blood pO2 is drastically reduced.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7516001
TI  - Enoximone in chronic stable angina: a double-blind placebo-controlled cross-over
      trial.
AB  - Enoximone, a phosphodiesterase inhibitor (PDEI), has both positive inotropic and
      vasodilatory properties. We examined the effect of a single oral dose of
      enoximone as compared with placebo on myocardial ischaemia and global left
      ventricular (LV) function using both exercise ECG and Doppler measurements of
      aortic blood flow, respectively. Twenty patients (16 men, 4 women) with a mean
      age of 59 years and stable angina were studied. Total exercise duration was
      significantly longer after enoximone as compared with placebo treatment, with a
      mean difference of 22.8 s (p = 0.003). Times (mean +/- SD) to onset of angina and
      development of significant ST-segment decrease were similar after placebo (454 +/
      101 and 352 +/- 155 s, respectively) or enoximone (500 +/- 155 and 413 +/- 192
      s, respectively), although both showed trends in favour of enoximone. As compared
      with placebo, significantly higher heart rate (HR) was measured for enoximone
      both at rest (75 +/- 18 vs. 90 +/- 22 beats/min, p < 0.01) and on recovery from
      exercise (81 +/- 18 vs. 89 +/- 19 beats/min, p < 0.05). Enoximone had no
      significant effect on systolic or diastolic blood pressure (SBP, DBP) or rate
      pressure product (RPP) generated at rest or during exercise. Changes in both
      acceleration and velocity of aortic blood flow during exercise were similar after
      administration of enoximone or placebo. We showed that a single oral dose of
      enoximone is well tolerated in patients with ischaemic heart disease, improving
      both exercise capacity and favourably influencing ST-segment changes with no
      increase in adverse events or significant haemodynamic disturbances.

PMID- 7515999
TI  - Effects of single intravenous administration of urapidil and diltiazem in
      patients with nonfixed pulmonary hypertension secondary to chronic obstructive
      lung disease.
AB  - In patients with chronic obstructive lung disease (COLD), pulmonary hypertension
      (PH) often develops in addition over the course of years. In this study, the
      acute effects of urapidil and diltiazem in patients with mild PH secondary to
      COLD were investigated. Eighteen male and 2 female patients, aged 42-78 years,
      received in randomized, single-blind fashion single intravenous (i.v.) doses of
      either urapidil (35-50 mg, n = 10) or diltiazem (25 mg, n = 10). Mean pulmonary
      artery pressure (MPAP), pulmonary wedge pressure (PWP), mean arterial blood
      pressure (BP) (MAP), and arterial and central venous blood gases were determined
      at rest and during exercise (starting with 25 W with increases in 25-W steps)
      before and after drug administration. Urapidil caused a significant reduction in
      MPAP (from 19 +/- 7 to 15 +/- 4 mm Hg, p < 0.01), PWP (from 9 +/- 3 to 7 +/- 2 mm
      Hg, p < 0.05), but not significantly in MAP at rest, whereas with diltiazem only
      MAP was decreased (from 103 +/- 14 to 98 +/- 12 mm Hg, p < 0.05) and MPAP and PWP
      were not significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516003
TI  - Angiotensin II (AII)-induced myocyte necrosis: role of the AII receptor.
AB  - Pathophysiologic levels of angiotensin II (AII) produce myocyte necrosis. We
      investigated whether the cardiotoxic effects of AII are mediated through the AII
      type I receptor (AT1). Seven groups (4-6 rats/group) were given AII (150 ng/min)
      alone or in combination with the AT1 antagonist losartan (7.5 mg/day). Groups
      were as follows: A1, A4, and L1 received AII for 2 days; A2 and L2 received AII
      for 9 days; and A3 and L3 received AII for 2 days and again for 2 days 5 days
      later. Groups L1, L2, and L3 also received losartan 2 days before and throughout
      the AII infusion period. All rats except those in group A4 were killed at the end
      of their respective infusion periods (group A4 rats were killed 7 days after
      infusion). Group A1 had multifocal areas of recent myocyte injury. Groups A2 and
      A4 had multifocal scars and only a few new areas of myocyte damage. Group A3, in
      addition to scar formation, had de novo areas of necrosis. There was no evidence
      of myocyte necrosis in groups L1, L2, and L3. Thus, AII-related myocyte necrosis
      is receptor mediated. Moreover, a chronic increase in AII appears to cause
      cardioprotective downregulation of the AT1 receptor.

PMID- 7516002
TI  - Epicardial and endocardial coronary microvascular responses: effects of ischemia
      reperfusion.
AB  - To examine whether endocardial microvascular function is preferentially impaired
      by ischemia and reperfusion, we studied endothelium-dependent responses of
      epicardial and endocardial coronary microvessels (130-220 microns) from control
      pigs and from pigs subjected to 1-h regional myocardial ischemia (circumflex
      occlusion) followed by 1-h reperfusion (n = 8) in vitro using videomicroscopy. In
      control animals (n = 8), no significant transmural differences were apparent in
      microvascular responses to the endothelium-dependent agents bradykinin or the
      calcium ionophore A23187, to the endothelium-independent agent sodium
      nitroprusside (SNP), or to adenosine. Serotonin caused a slight but statistically
      insignificant greater relaxation of endocardial than of epicardial microvessels.
      After ischemia-reperfusion, relaxations to all endothelium-dependent agents
      (serotonin, bradykinin, A23187) and to adenosine were significantly reduced (p <
      0.05 for all agents) as compared with the respective control responses. There
      were no significant differences between epicardial and endocardial responses in
      the ischemia-reperfusion group for any of the vasoactive agents. Endothelium
      independent responses to SNP were not affected by ischemia-reperfusion,
      indicating no alteration in the ability of vascular smooth muscle to relax
      through guanylate cyclase-mediated mechanisms. Control epicardial microvascular
      responses were examined after endothelial denudation and after pretreatment with
      NG-monomethyl-L-arginine (L-NMMA), indomethacin, or glibenclamide.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7516004
TI  - Reduction in myocardial infarct size by the new potassium channel opener
      bimakalim.
AB  - We examined the effect of a new potassium channel opener, bimakalim, on
      myocardial infarct size (IS) in dogs. Barbital-anesthetized dogs were subjected
      to 90 min of left circumflex coronary artery (LCX) occlusion followed by 5-h
      reperfusion. Bimakalim (3 micrograms/kg bolus followed by 0.1 microgram/kg/min
      intravenously, i.v.) was initiated either 15 min before LCX occlusion and
      continued throughout the experiments in one group of animals or initiated 5 min
      before and throughout reperfusion in a second group. A third group of dogs
      received i.v. vehicle (control) 15 minutes before LCX occlusion and throughout
      the remainder of the experiment. IS was determined by triphenyltetrazolium
      histochemical staining, regional myocardial blood flow (RMBF) by the radioactive
      microsphere technique, and neutrophil migration by measurement of tissue
      myeloperoxidase (MPO) activity. Bimakalim reduced mean aortic blood pressure
      (MBP, 25 mm Hg) during the occlusion and reperfusion periods in the group of dogs
      that received the drug throughout the experiment and reduced in BP, during
      reperfusion when administered immediately before the reperfusion period. In
      addition, bimakalim increased LCX coronary artery blood flow (CBF) and increased
      regional myocardial blood flow (RMBF) primarily during reperfusion in both drug
      treated groups, with the greatest increase to the subepicardial region. During
      occlusion, however, bimakalim had no effect on collateral blood flow to the
      ischemic region. In all three groups, left ventricular (LV) mass, area at risk
      (AAR) mass, and percentage of he left ventricle at risk were similar.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7516005
TI  - Ischaemia/reperfusion enhances phenylephrine-induced contraction of rabbit aorta
      due to impairment of neuronal uptake.
AB  - We studied the effect of ischaemia and reperfusion on vasoconstrictor and
      vasodilator mechanisms. Anaesthetized rabbits were subjected to 4-h abdominal
      aortic occlusion and 1-h reperfusion in vivo. Segments of the abdominal
      (ischaemic-reperfused) and thoracic (control) aorta were then removed for in
      vitro studies. Ischaemia/reperfusion had no significant effect on relaxant
      responses to either acetylcholine (ACh:endothelium-dependent) or sodium
      nitroprusside (SNP:endothelium-independent). The sensitivity of the aorta to
      contraction by phenylephrine was significantly increased in aortic rings with or
      without endothelium (by 2.2- and 3.7-fold, respectively), but was not different
      after 4-h ischaemia without reperfusion. In contrast, responses to methoxamine,
      serotonin, and U46619 were not affected by ischaemia/reperfusion. Moreover, the
      relative increase in aortic sensitivity to phenylephrine was prevented by
      treatment of control and ischaemic-reperfused aortic rings with the neuronal
      uptake inhibitor cocaine (10(-5) M). These results suggest that after 4-h
      ischaemia, reperfusion damages sympathetic neuronal uptake mechanisms in rabbit
      aorta. As a result, phenylephrine, an agonist normally susceptible to neuronal
      uptake, may exert more potent contractile effects. Endothelium-dependent and
      endothelium-independent relaxant mechanisms in the aorta appear to be resistant
      to acute ischaemia and reperfusion.

PMID- 7516006
TI  - Chronotropic cardiac effects of falipamil in conscious dogs: interactions with
      the autonomic nervous system and various ionic conductances.
AB  - The chronotropic cardiac effects of falipamil were studied in conscious dogs with
      chronic atrioventricular (AV) block. Falipamil (0.5-2 mg/kg) initially increased
      atrial rate dose dependently. After atropine and atropine-pindolol, falipamil (2
      mg/kg) decreased atrial rate, but after pindolol, it did not modify atrial rate.
      After atropine-pindolol-phenoxybenzamine, atropine-pindolol-yohimbine, atropine
      pindolol-verapamil, and atropine-pindolol-quinidine pretreatment, falipamil
      produced atrial bradycardia. Falipamil dose-relatedly decreased ventricular rate.
      Falipamil (2 mg/kg) decreased ventricular rate after atropine, pindolol, and
      atropine-pindolol more than under basal conditions. After the other four
      pretreatments, it also produced ventricular bradycardia. Falipamil did not affect
      mean blood pressure (MBP) at any dose. These results (a) show that the initial
      atrial cardio-acceleration produced by falipamil results from its direct
      vagolytic action; (b) show that absence of atrial bradycardia results from
      buffering by the vagolytic effect and/or a relatively low basal atrial rate; (c)
      suggest that the falipamil ventricular bradycardia is partly buffered by the
      vagolytic effect, norepinephrine (NE) release, and involvement of alpha 2
      adrenoceptors; (d) exclude involvement of postsynaptic muscarinic, alpha- and
      beta-adrenoceptors, and of the slow calcium current in the mechanism(s) by which
      falipamil decreases cardiac automaticity; and (e) suggest possible involvement of
      a quinidine-sensitive current in this (these) mechanism(s).

PMID- 7516009
TI  - Increased concentrations of angiotensin-converting enzyme in the intimal
      hyperplasia of experimental vein grafts.
AB  - Local renin and angiotensin-converting enzyme (ACE) activity were recently
      implicated in development of intimal hyperplasia after vascular injury, but
      little is known about the local responses of angiotensin I/II (AI/AII) and local
      ACE activity in vein graft physiology. The activity of the local ACE system of
      experimental vein grafts was examined in this study. The right carotid artery was
      divided and bypassed in 21 New Zealand White rabbits, using the right external
      jugular vein. The left external jugular vein was used as a control. Veins and
      vein grafts were harvested after 14 days. Rings from both vessels were studied in
      vitro under isometric tension, and dose-response curves to AI and AII were
      obtained. AI responses were also measured in the presence of captopril. The
      tissue concentrations of ACE in both vessels were estimated by spectrophotometry
      and were localized by immunohistochemistry. The responses of the veins to AI and
      AII were multiphasic, whereas the responses of vein grafts were sigmoid-shaped.
      Incubation of vein grafts with captopril significantly decreased the sensitivity
      to AI (p < 0.0001). Immunohistochemical localization identified ACE in the
      endothelial layer of the veins and vein grafts, but also at a greater density in
      the intimal hyperplasia of the vein graft. The concentration of ACE was 1.92 +/-
      0.16 U/g (wet weight; mean +/- SEM, n = 9) in vein grafts and 1.39 +/- 0.05 U/g
      in the veins (38% increase, p < 0.05, n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516007
TI  - Localization of endothelin immunoreactivity and demonstration of constrictory
      endothelin-A receptors in human coronary arteries and veins.
AB  - Strong immunoreactivity for endothelins (ETs) was observed in the endothelium of
      both human epicardial coronary arteries and veins. The contractile responses to
      ET-1, ET-2, and ET-3 were investigated in isolated circular human coronary vessel
      segments. ET-1, ET-2, and ET-3 induced significantly higher maximum contraction
      (measured in percentage of contraction induced by 60 mM potassium) and more
      potent responses in veins as compared with arteries. ET-1 as compared with ET-2
      induced equal maximum contraction and equipotent responses both when tested in
      arteries and veins, whereas ET-3 induced lower maximum contraction and less
      potent responses in both vessel types. FR 139317, a selective ETA receptor
      antagonist, significantly decreased the potency of ET-1 and ET-2 responses in
      both human coronary arteries and veins, but the maximum effect obtained did not
      change significantly. The existence of ET immunoreactivity (IR) in endothelial
      cells from both human coronary arteries and veins indicates that ETs may be
      released endogenously. The effect of the selective ETA receptor antagonist FR
      139317 indicates that the contraction induced by ET-1 and ET-2 in both arteries
      and veins is mediated by ETA receptors.

PMID- 7516008
TI  - Efficacy of angiotensin-converting enzyme inhibition and AT1 receptor blockade on
      cardiac pump performance after myocardial infarction in rats.
AB  - To determine whether cardiac unloading by inhibition of angiotensin I (AI) to AII
      conversion by captopril or blockade of the AII receptor (AT1) by losartan was
      more effective in prevention of the detrimental hemodynamic consequences of
      myocardial infarction (MI), inhibition of metabolic production of AII by
      captopril was compared with blockade of AT1 with losartan in Sprague-Dawley rats
      with large MI. Infarcts were created by surgical occlusion of the left main
      coronary artery and oral drug therapy initiated immediately and continued until
      hemodynamic evaluation seven days later. Heart weight was unchanged in untreated
      infarcted animals, whereas captopril reduced heart weight in control animals and
      losartan increased heart weight in infarcted animals. Left ventricular (LV) peak
      systolic blood pressure (SBP) was lower in treated and untreated infarcted
      animals. Although captopril reduced end-diastolic pressure (EDP) to a greater
      degree than losartan, all infarcted group showed an increase in this parameter
      with respect to similarly treated controls. LV peak rates of pressure increase
      and decay in infarcted hearts were decreased significantly more by captopril than
      by losartan administration. Captopril also impaired right side cardiac function
      more than losartan when peak rate of pressure increase was evaluated. Thus,
      inhibition of the effects of AII during cardiac failure improved but did not
      normalize cardiac pump performance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516010
TI  - Role of the endothelium and cyclic GMP in renal vasodilator responses to
      cryptolepine in rats.
AB  - Isolated perfused rat kidney was used to examine the possible mechanisms involved
      in the hypotensive/vasodilator actions of cryptolepine. In kidneys preconstricted
      by phenylephrine (PE 5-7.5 x 10(-7) M), cryptolepine at bolus doses of 2.5, 5,
      and 10 micrograms elicited dose-dependent reductions in perfusion pressure by
      29.8 +/- 4.1, 43.3 +/- 3.9, and 54.3 +/- 4.9 mm Hg, respectively. In the presence
      of indomethacin, cryptolepine-induced reduction in perfusion pressure was not
      significantly changed, suggesting a lack of a cyclooxygenase-mediated component
      in its renal vasodilator response. Removal of the endothelium with p
      bromophenacyl bromide (p-BPB 10 microM) inhibited the vasodilator response to
      cryptolepine 2.5, 5, and 10 micrograms to 10.2 +/- 1.8, 15.9 +/- 1.5, and 20.2 +/
      2.0 mm Hg, respectively (p < 0.01). The vasodilator response to acetylcholine
      (ACh 50 ng) was also reduced from a control value of 56.7 +/- 4.5 to 15.3 +/- 1.9
      mm Hg (p < 0.01); responses to sodium nitroprusside (SNP 5 micrograms) and
      isoprenaline (1 microgram) were not affected. In kidneys treated with
      hydroquinone (10(-5) and 10(-4) M), a specific inhibitor of endothelium-dependent
      vasodilation, cryptolepine- and ACh-induced vasodilation were inhibited dose
      dependently (p < 0.01). N omega-nitro-L-arginine (L-NNA 10(-5)-10(-4) M), a
      specific inhibitor of the synthesis/release of endothelium-derived relaxing
      factor/nitric oxide (EDRF/NO), attenuated the vasodilator response to
      cryptolepine and ACh (50 ng) dose dependently. At 10(-4) M L-NNA, cryptolepine
      induced vasodilation was reduced to 6.6 +/- 2.2 (2.5 micrograms), 10.9 +/- 2.2 (5
      micrograms), and 13.3 +/- 1.4 mm Hg (10 micrograms). L-Arginine (10(-4) and 3 x
      10(-4) M) but not D-arginine (10(-4) M) inhibited the effects of L-NNA, with
      vasodilatory effects of cryptolepine returning to control values, suggesting that
      the vasodilator material released by cryptolepine is EDRF, possibly NO. Methylene
      blue (MB 10(-4) M), the inhibitor of soluble guanylate cyclase which inhibited 50
      ng ACh and 5 micrograms SNP-induced vasodilation also reduced the vasodilatory
      responses to cryptolepine to 0.8 +/- 0.8 (2.5 micrograms), 4.2 +/- 4.2 (5
      micrograms), and 10.8 +/- 6.2 mm Hg (10 micrograms) suggesting that the effector
      pathway for cryptolepine-induced vasodilation is soluble guanylate cyclase-linked
      increase in cyclic GMP of vascular smooth muscle.

PMID- 7516011
TI  - Neurogenic vasodilation in rabbit hindlimb mediated by tachykinins and nitric
      oxide.
AB  - We investigated the role of nitric oxide (NO) in the mediation of nerve
      stimulation-induced vasodilation in skeletal muscle. Hindlimb blood flow and
      vascular resistance were measured in pentobarbital-anesthetized, paralyzed, and
      guanethidine-treated rabbits. Centrifugal electrical stimulation of the sciatic
      nerve bundle induced reproducible, frequency-, voltage-, and pulse duration
      dependent decrements in vascular resistance. The tachykinin antagonist CP-96,345
      (1 mg/kg intravenously, i.v.) attenuated the vasodilation induced by
      intraarterially (i.a.) administered substance P but not by adenosine.
      Furthermore, CP-96,345 attenuated the decrease in vascular resistance in response
      to nerve stimulation, from 22.9 +/- 3.2 to 4.5 +/- 4.1% of control resting
      resistance (p < 0.005), without affecting basal vascular resistance. An inhibitor
      of NO formation, N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg i.v.),
      increased vascular resistance from 6.1 +/- 0.5 to 9.1 +/- 1.2 resistance units (p
      < 0.05) and significantly attenuated the vascular response to i.a. administered
      substance P but not adenosine. Finally, nerve stimulation-induced reduction in
      vascular resistance was attenuated by L-NAME, from 22.6 +/- 2.7 to 7.0 +/- 1.0%
      of control (p < 0.001). These findings suggest that tachykinins and NO are
      involved in mediation of vasodilation in response to the present type of nerve
      stimulation. The data are consistent with the hypothesis that NO is produced
      subsequent to neural release of tachykinin-type transmitter(s).

PMID- 7516012
TI  - Molecular mechanism of cibenzoline-induced anticholinergic action in single
      atrial myocytes: comparison with effect of disopyramide.
AB  - The anticholinergic effects of cibenzoline were examined and compared with those
      of disopyramide in atrial myocytes isolated from guinea pig heart. The tight-seal
      whole-cell voltage clamp technique was performed with a patch pipette filled with
      guanosine-5'-triphosphate (GTP) or guanosine-5'-O-(3-thiotriphosphate) (GTP gamma
      S). In GTP-loaded cells, both acetylcholine (ACh) and adenosine (Ado) induced a
      specific K channel current through GTP-binding proteins by binding to the
      muscarinic and Ado receptors, respectively. Both cibenzoline and disopyramide
      suppressed the ACh-induced K current effectively in a concentration-dependent
      manner. The concentrations for half-maximal inhibition of the current (EC50)
      caused by cibenzoline and disopyramide were 8 and 3 microM, respectively. In GTP
      gamma S-loaded cells, the K current was irreversibly activated because GTP
      binding proteins were directly elicited by GTP gamma S. Cibenzoline effectively
      caused a decrease in the GTP gamma S-induced K current, whereas the extent of
      disopyramide action on the GTP gamma S-induced K current was much less.
      Cibenzoline also caused significant inhibition of Ado-induced K current in GTP
      loaded cells. However, the action of disopyramide was less effective in
      inhibiting Ado-induced K current. These results indicate that cibenzoline has
      less potent anticholinergic effects than disopyramide in atrial myocytes. In
      addition, cibenzoline effectively inhibits the muscarinic K channel itself and/or
      GTP-binding proteins coupled to the channel, whereas the effect of disopyramide
      is attributed mainly to blockade of muscarinic receptors. These findings provide
      novel understanding of the molecular mechanism of anticholinergic action of
      cibenzoline.

PMID- 7516013
TI  - High-calcium diet prevents salt-induced hypertension and impairment of renal
      hemodynamics in young spontaneously hypertensive rats.
AB  - We studied the effects of a high Ca (4.07%) diet on mean arterial pressure (MAP)
      and renal hemodynamics in young (6 weeks) spontaneously hypertensive rats (SHR)
      fed a normal (0.66%) or a high-salt (8.00%) diet for 4 weeks. The high-salt diet
      accelerated development of hypertension (213 +/- 5 vs. 159 +/- 2 mm Hg, p < 0.01)
      and increased renal vascular resistance (RVR) (26.4 +/- 2.3 vs. 18.2 +/- 1.2 U, p
      < 0.01) in young SHR. Simultaneous Ca supplementation prevented the salt-induced
      increase in MAP (158 +/- 3 mm Hg, p < 0.01) and in RVR (17.3 +/- 1.1 U, p <
      0.01). The high-Ca diet did not affect MAP (151 +/- 3 mm Hg, NS) and RVR (17.4 +/
      1.3 U, NS) in young SHR fed a normal salt diet. RVR and MAP were positively
      correlated in all rats (r = 0.634, n = 38, p < 0.001). The high-Ca diet also
      prevented salt-induced left ventricular (LV) hypertrophy. Dietary Ca
      supplementation attenuated the increased salt sensitivity of arterial pressure,
      possibly by normalizing renal hemodynamics, in salt-loaded young SHR.

PMID- 7516014
TI  - Effects of perindopril on serum lipids in hypertensive patients with
      hyperlipidemia.
AB  - The effect of the angiotensin-converting enzyme (ACE)-inhibitor perindopril on
      serum lipids and apolipoprotein concentrations were assessed in a multicenter,
      randomized, double-blind, placebo-controlled study in 51 hyperlipidemic patients
      treated for mild hypertension. Perindopril was given as a single morning dose (4
      mg) for 6 weeks. During the treatment period, blood pressure (BP) was
      significantly (p < 0.001) reduced from 159/99 to 148/90 mm Hg by verum treatment
      and from 158/101 to 151/95 mm Hg (NS) by placebo treatment. Neither total
      cholesterol and triglycerides nor high-density-lipoprotein and apolipoprotein AI
      and B levels were significantly altered by drug treatment as compared with
      placebo. Although perindopril had good antihypertensive effect in patients with
      mild hypertension and hyperlipidemia, it had no adverse effects on lipid
      metabolism in these patients. Therefore, perindopril is recommended for
      antihypertensive treatment, especially in hypertensive patients with concomitant
      hyperlipidemia.

PMID- 7516017
TI  - Neutrophil adherence to rat cardiac myocyte by proinflammatory cytokines.
AB  - Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) in cardiac
      myocytes may be a critical step in inflammation associated with ischemia
      reperfusion injury. We investigated the involvement of tumor necrosis factor
      alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) on neutrophil
      myocyte adhesion; These cytokines are increased in plasma of patients with acute
      myocardial infarction (AMI). ICAM-1 expression on cultured neonatal rat cardiac
      myocytes was determined through immunohistochemical and enzyme-linked
      immunosorbent assay (ELISA) analysis. ICAM-1 mRNA expression in myocytes was
      investigated by Northern blot hybridization. Rat neutrophils isolated from
      peripheral blood (PB) were used for adherence assay. In immunohistochemical
      study, cultured neonatal rat cardiac myocytes constitutively expressed ICAM-1
      molecules. In ELISA analysis, ICAM-1 molecule expression on myocytes was
      significantly stimulated by TNF-alpha (100 U/ml), but not by IL-6 (100 U/ml) or
      IL-8 (100 ng/ml) dose dependently. The effect of TNF-alpha was observed as early
      as 6 h after stimulation. Levels of ICAM-1 mRNA were very low or almost
      undetectable in unstimulated myocytes, but its expression was markedly induced
      after exposure to TNF-alpha for 3 h. IL-6 and IL-8 showed no effect on ICAM-1
      mRNA accumulation. Adhesion of rat neutrophils to myocytes was stimulated by TNF
      alpha, and the effect of TNF-alpha on adherence was significantly inhibited by an
      anti-ICAM-1 monoclonal antibody (MoAb). These results show that TNF-alpha, but
      not IL-6 and IL-8, promotes neutrophil-myocyte adhesion through ICAM-1
      expression, suggesting involvement of TNF-alpha in inflammation associated with
      ischemia-reperfusion injury.

PMID- 7516016
TI  - Is an intracellular renin-angiotensin system involved in control of cell
      communication in heart?
AB  - The possible influence of an intracellular renin-angiotensin system (RAS) on
      control of cell communication in heart muscle was investigated in cell pairs
      isolated from adult rats. Junctional conductance (gj) was measured with two
      separated voltage-clamp circuits. Intracellular dialysis of angiotensin I (AI 10(
      8) M) caused a decrease in gj of 76% (SE +/- 3.4) (p < 0.05) in 7 min. The effect
      of AI appears to be due mainly to its conversion to AII because enalaprilat (10(
      9) M) dialysed into the cell caused an appreciable reduction in the effect of AI.
      AII (10(-8) M) alone caused a decrease in gj of 60% (SE +/- 3.8) (p < 0.05) in 45
      s. The effect of AII on gj was suppressed by previous inhibition of protein
      kinase C (PKC), but enalaprilat could not alter the effect of the peptide. The
      results indicate that synthesis of AII inside cardiac myocytes plays an important
      role in modulation of gj and consequently on propagation of the electrical
      impulse in heart. The effect of AII on gj was blocked by DuP-753 (10(-9) M)
      administered intracellularly, whereas (Sar1Val5AlA8) AII also caused a slight
      decrease (1.97 +/- 0.07%) in gj. These findings indicate that an intracellular
      receptor is involved in the effect of the peptide on gj.

PMID- 7516015
TI  - Bradykinin accounts for improved postischemic function and decreased glutathione
      release of guinea pig heart treated with the angiotensin-converting enzyme
      inhibitor ramiprilat.
AB  - We investigated the role of bradykinin (BK) in cardioprotection elicited by
      angiotensin-converting enzyme (ACE) inhibition is isolated guinea pig heart
      performing pressure-volume work. Cardiac output (CO), coronary blood flow (CBF),
      and external heart work (EHW) were determined before and after ischemia and
      reperfusion (15 min each). Furthermore, the glutathione (GSH) content of hearts
      and the release of glutathione in coronary venous effluent were measured, as was
      lactate production. Addition of the ACE-inhibitor ramiprilat (RT) to the
      perfusate throughout the experiment improved postischemic function significantly
      (55% recovery of EHW for 25 microM RT vs. 30% for controls). RT was
      cardioprotective even if only given at onset of reperfusion (50% recovery). BK
      (0.1 and 1 nM) was similarly beneficial (55 and 76% recovery of EHW,
      respectively). The BK2-receptor antagonist HOE 140 (10 nM) inhibited the RT
      effect and attenuated the effect of 1 nM BK. Total CBF during reperfusion,
      lactate production, intracellular levels of GSH, and release of oxidized GSH
      (GSSG) did not differ among the groups. In contrast, release of reduced GSH
      during the first 5 min of reperfusion was considerably influenced by
      pharmacologic intervention, correlating inversely with postischemic heart
      function. Coapplication of Hoe 140 prevented the changes in GSH release. Our
      results demonstrate that BK, formed endogenously in the heart, is responsible for
      cardioprotection by the ACE inhibitor RT in isolated guinea pig heart and
      decreases GSH release during reperfusion. The exact mechanisms leading to
      hemodynamic improvement and metabolic changes by BK remain unclear.

PMID- 7516018
TI  - Comparison of the cardiac electrophysiologic effects of NE-10064 with sotalol and
      E-4031 and their modification by simulated ischaemia.
AB  - The electrophysiologic effects of a new anti-arrhythmic agent NE-10064 were
      compared with known class III drugs, E-4031 and sotalol, in sheep Purkinje fibres
      paced at 1 Hz under normal and simulated ischaemic conditions. NE-10064 0.3-3
      microM and sotalol 0.3-300 microM prolonged action potential duration at 90% of
      repolarization (APD90) and effective refractory period (ERP) concentration
      dependently without affecting APD50 under normal conditions. E-4031 0.3-300
      microM prolonged APD50, APD90, and ERP concentration dependently. Percentage
      increases in APD90 of 20 +/- 6, 27 +/- 6, and 33 +/- 9 were calculated for NE
      10064 3 microM, sotalol 300 microM, and E-4031 1 microM under normal conditions,
      respectively. The concentration-response curves for all three drugs were shifted
      to the right under simulated ischaemic conditions. The shift was more marked for
      NE-10064 and sotalol. Percentage increases in APD90 of 8 +/- 5, 13 +/- 2, and 23
      +/- 4 were observed with NE-10064 3 microM, sotalol 300 microM, and E-4031 1
      microM during simulated ischaemia. NE-10064 exhibits electrophysiologic
      characteristics similar to those of known class III agents. Its ability to
      prolong APD90 under normal conditions may explain its antiarrhythmic action in
      vivo.

PMID- 7516019
TI  - Relationships between acute and chronic beta-blocking effects of bisoprolol in
      healthy volunteers: a practical approach to predict intensity of beta-blockade.
AB  - Bisoprolol is a selective beta 1-adrenoceptor antagonist devoid of partial
      agonist activity that can be used for treatment of chronic and acute myocardial
      ischemia. In this condition, it is important to demonstrate that a stable beta
      blocking effect at steady state can be predicted by a mathematical model
      determined by plasma concentration-effect relationship after an acute intravenous
      (i.v.) dose. This relation was studied in 10 healthy volunteers in a double
      blind, randomized, cross-over, placebo-controlled study after a 5-min i.v.
      infusion of bisoprolol (5 mg) or placebo. Standardized exercise tests were
      recorded at different times for 48 h after infusion with simultaneous bisoprolol
      assay (high-performance liquid chromatography, HPLC) in plasma. After a 1-week
      interval, subjects received oral bisoprolol (10 mg once daily) for 5 days and
      exercise tests were repeated on day 5 before and 2, 3, and 4 h after dosing, with
      bisoprolol plasma level determined simultaneously. In the acute period,
      bisoprolol significantly decreased exercise heart rate (HR: peak effect -20.5 +/-
      4%) as compared with placebo. There was a direct relationship (no hysteresis)
      between beta-blockade and plasma concentrations with a sigmoid (7 subjects) or a
      linear (3 subjects) best-fit model. After repeated bisoprolol administration,
      steady-state plasma levels were achieved and 88% of the observed decreases in
      exercise HR were within the 95% confidence interval (CI) for individual
      prediction. These data suggest that bisoprolol-induced beta-blockade after
      repeated oral dosing can be predicted by single-test i.v. dose administration.

PMID- 7516020
TI  - Tetrachlorodecaoxygen, a wound healing agent, produces vascular relaxation
      through hemoglobulin-dependent inactivation of serotonin and norepinephrine.
AB  - We investigated the vasoactive actions of the wound-healing agent
      tetrachlorodecaoxygen (TCDO). TCDO (20 microM) had no direct effect on tone in
      isolated calf pulmonary arteries precontracted with potassium with or without 1
      microM reduced hemoglobin under O2 or N2 atmosphere. However, TCDO, in a reduced
      hemoglobin-dependent manner, attenuated contraction produced by serotonin,
      associated with spectral changes consistent with destruction of serotonin. The
      loss of tone induced by serotonin catalyzed by TCDO plus reduced hemoglobin was
      not altered in the presence of superoxide dismutase (SOD) plus catalase. TCDO
      plus reduced hemoglobin also produced rapid relaxation of isolated rabbit aorta
      precontracted with norepinephrine (NE), whereas with phenylephrine (PE)-induced
      bone, the observed relaxation was slow to develop. Neither did TCDO, with or
      without reduced hemoglobin, alter soluble guanylate cyclase activity in pulmonary
      artery. Thus, a highly reactive species produced by interaction of TCDO with
      reduced hemoglobin appears to attenuate the contractile actions of serotonin, NE,
      and PE, selectively potentially by destroying these vasoactive agents. The
      vasodilator actions of TCDO (plus reduced hemoglobin) may contribute to wound
      healing by increasing nutrient blood flow and O2 delivery needed for repair
      processes and bactericidal activity.

PMID- 7516021
TI  - Possible mechanisms of vasoinhibitory effects of mequitazine, an antiallergic
      agent, on the contractions of isolated rat aorta induced by K+, phenylephrine, 5
      hydroxytryptamine, and Ca2+.
AB  - Mequitazine, 10-(3-quinuclidinylmethyl) phenothiazine, inhibited contractile
      responses to KCl, phenylephrine (PE), 5-hydroxytryptamine (5-HT), and Ca2+ in rat
      aorta. Indomethacin or removal of endothelium did not affect the inhibitory
      effect of mequitazine on the responses to PE. In Ca(2+)-free medium containing
      EGTA and nifedipine, mequitazine inhibited both residual response to PE and
      subsequent response to Ca2+ in the presence of PE. Mequitazine potentiated the
      relaxation to nitroglycerin (NTG) and isoproterenol. In the presence of
      forskolin, mequitazine did not cause further potentiation of NTG relaxation.
      Mequitazine relaxation was slightly inhibited by nifedipine and was potentiated
      by theophylline. The relaxation was not affected by zaprinast, methylene blue, W
      7, propranolol, cimetidine, glyburide, or tetraethylammonium. Tissue level of
      cyclic AMP in rat aorta was increased by mequitazine. These results suggests that
      mequitazine may inhibit voltage-operated Ca2+ channels (VOC) and increases the
      level of cyclic AMP.

PMID- 7516022
TI  - Effects of MS-551, a new class III antiarrhythmic drug, on programmed stimulation
      induced ventricular arrhythmias, electrophysiology, and hemodynamics in a canine
      myocardial infarction model.
AB  - We examined the effects of MS-551 (1,3-dimethyl-6-[(2-[N-(2-hydroxyethyl)-3-(4-
      nitrophenyl)propylamino]ethylamino] 2,4(1H,3H)-pyrimidinedione hydrochloride), a
      new class III antiarrhythmic drug, on programmed electrical stimulation (PES)
      induced ventricular arrhythmias, the effective refractory period (ERP),
      intraventricular conduction, and hemodynamics in a canine myocardial infarction
      (MI) model. MS-551 was administered intravenously (i.v.) in two consecutive
      doses; the first dose (low dose) was 0.5 mg/kg/min after a bolus injection of 0.3
      mg/kg, and a second dose (high dose) was 0.1 mg/kg/min after a bolus injection of
      0.3 mg/kg. PES induced ventricular tachycardia (VT) or ventricular fibrillation
      (VF) in 10 of 12 animals. MS-551 abolished or lessened the ventricular
      arrhythmias in 7 of 10 animals at both doses. ERP was significantly prolonged by
      MS-551 in both the normal and infarcted zones in a dose-dependent fashion.
      Ventricular conduction of a premature excitation induced by a premature
      stimulation with various coupling intervals was decreased only at a coupling
      interval approximating that of ERP. MS-551 at either low or high dose did not
      significantly change the heart rate (HR), mean blood pressure (MBP), cardiac
      output (CO), or maximum rate of increase in left ventricular pressure (LVP)
      significantly. MS-551 produced a suppression of the PES-induced ventricular
      arrhythmias through prolongation of ERP without having any significant effect on
      hemodynamics in a canine MI model.

PMID- 7516024
TI  - Mathematical model of antiviral immune response. III. Influenza A virus
      infection.
AB  - We present an approach to studying theoretically the regularities and the kinetic
      characteristics of influenza A virus (IAV) infection in man. The estimates of the
      "numbers" (Zinkernagel et al., 1985) characterizing evolutionary established
      interferon and immune responses in uncomplicated IAV infection are explored by
      developing a multiparameter mathematical model which allows direct quantitative
      references to the biological reality. The system of equations of the mathematical
      model of antiviral immune response, applied earlier to acute hepatitis B virus
      infection (Marchuk et al., 1991a, b), is modified and extended to describe the
      joint reaction of the interferon and immune systems in IAV infection. Macrophages
      infiltrating the airway's epithelium are considered to be the principal source of
      interferon that induces antiviral resistance in lung epithelial cells. The model
      is formulated as a delay-differential system with about 60 parameters
      characterizing the rates of various processes contributing to the typical course
      of IAV infection. The key aspect of the adjustment between the model and various
      data on the immunity to influenza is the derivation of a consistent data set--the
      generalized picture of uncomplicated IAV infection. It serves as a consistent
      theoretical definition of the structure of the normal course of the infection and
      the antiviral immune response suitable for model fitting. The parameter estimates
      for the processes considered in the model are carefully discussed. The
      quantitative model is used to study the organization and dynamic properties of
      the processes contributing to IAV infection. The threshold condition for immune
      protection of virus-free host to infection with IAV is analyzed. The relative
      roles of humoral, cellular and interferon reactions for the kinetics of the
      uncomplicated IAV infection are studied. The contribution of parameters of virus
      sensitive tissue, interferon and IAV-specific immune processes to the variations
      of duration and severity of the infection is quantitatively estimated by
      sensitivity studies. It is shown that the variations in the parameters of a virus
      epithelial cell system are more influential on the severity of the infection
      rather than that of the antiviral immune response. The need for fine co
      ordination of the kinetics of the non-specific interferon response and the
      adaptive antigen-specific immune reactions to provide recovery from the infection
      is illustrated.

PMID- 7516025
TI  - Origin of spindle-shaped cells in Kaposi sarcoma.
AB  - Adult skin microvascular endothelial cells derived from new born foreskin were
      grown and maintained in tissue culture with and without dibutyryl cyclic AMP (DC
      AMP) and isobutyl methyl xanthine (IMX). Whereas in the presence of DC-AMP and
      IMX, the cells showed the typical cobblestone appearance of endothelium, in the
      absence of these agents the cultured cells permanently converted to a spindle
      shaped configuration. Because this phenomenon of transdifferentiation also occurs
      in the presence of specific cytokines, the profile of which is notoriously
      altered in acquired immunodeficiency syndrome (AIDS), the findings support the
      concept that in Kaposi sarcoma the spindle-shaped cells derive from dysfunction
      in the microvascular environment.

PMID- 7516023
TI  - Antithrombotic effects of DMP 728, a platelet GPIIb/IIIa receptor antagonist, in
      a canine model of arterial thrombosis.
AB  - The platelet glycoprotein IIb/IIIa receptor (GPIIb/IIIa, fibrinogen receptor)
      represents the final common pathway for platelet aggregation. Inhibition of
      GPIIb/IIIa with antibodies or peptides containing the RGD sequence has been
      reported to prevent arterial thrombosis. We examined DMP 728 [(cyclic[D-2-amino
      butyryl-N2-methyl-L-arginyl-glycyl-L-aspartyl-3-(a min o- methyl-benzoic acid],
      methanesulfonic acid salt], a cyclic peptidomimetic, GPIIb/IIIa receptor
      antagonist, for prevention of thrombosis and rethrombosis in a canine model of
      carotid artery thrombosis. Dogs were anesthetized, and both carotid arteries were
      instrumented with an electrode, a flow probe, and a stenosis. A 300-microA
      current was applied to the intimal surface in the right carotid artery (RCA,
      control) through the electrode; time to occlusive thrombus formation and thrombus
      mass was noted. The RCA served as the control vessel; the left carotid artery
      (LCA) served as the test vessel after DMP 728 administration (0.1 or 1. mg/kg,
      intravenously, i.v.). As compared with controls, occlusive thrombus formation was
      reduced by both doses of DMP 728 (control 100% n = 12; 0.1 mg/kg i.v. 17%, p <
      0.05, n = 6; 1.0 mg/kg i.v. 0%, p < 0.05, n = 6), time to occlusion was increased
      (p < 0.05), and thrombus weight was reduced (p < 0.05). Ex vivo platelet
      aggregation was inhibited in all groups. In a second group of animals, a carotid
      artery thrombus was formed and lysed with anisoylated plasminogen activator
      complex (APSAC; 0.05 U/kg intraarterially, i.a.) with or without DMP
      728.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516026
TI  - Phenotypic characterization of human B-lymphocyte subpopulations, particularly
      human CD5+ B-lymphocyte subpopulation within the mantle zones of secondary
      follicles.
AB  - We have investigated the precise distribution of human B-lymphocyte
      subpopulations (CD5+ B lymphocyte, Leu-8+ lymphocyte, immunoglobulin D (IgD)+
      lymphocyte, alkaline phosphatase (ALPase)+ B lymphocyte and bcl-2 protein+ B
      lymphocyte) within the mantle zones (MZs) and phenotypic characterization of
      human CD5+ B lymphocytes using immunohistochemical techniques and flow cytometric
      analysis. IgD+ lymphocytes and ALPase B lymphocytes were confined to the inner
      layer and outer layer of the MZs of secondary follicles, respectively. CD5+ B
      lymphocytes and Leu-8+ B lymphocytes were mostly located in the inner layer of
      the MZs. Bcl-2 protein+ B lymphocytes were seen throughout the MZs. The precise
      distribution pattern of human B-lymphocyte subpopulations may help further
      understanding of the histogenesis and features of B-cell lymphomas, particularly
      mantle cell-derived lymphomas as well as the B-cell differentiation pathway. A
      minor population of CD5+ B lymphocytes expressed IgD. Almost all the CD5+
      lymphocytes did not express ALPase. The data support the fact that CD5+ B
      lymphocytes are located more in the inner layer than in the outer layer of the
      MZs. Leu-8 and bcl-2 protein were detected in a large population of CD5+ B
      lymphocytes. In addition, Ki-67 antigen was not expressed on the CD5+ B
      lymphocytes. The data suggest that human CD5+ B lymphocytes may be long-living
      and resting (G0 and G1a stage) cells possessing the capability of continuously
      recirculating between blood and lymph nodes to participate in some immune
      responses. Moreover, Leu-8 and CD44 were detected in the majority of CD5+ B
      lymphocytes but intercellular adhesion molecule-1 (ICAM-1) and very late antigen
      4 (VLA-4) were detected in the minority. The data may account for a high
      percentage of Leu-8 and CD44 expression and a low percentage of ICAM-1 and VLA-4
      expression on B-chronic lymphocytic leukemia (B-CLL), which is considered to be a
      neoplastic counterpart of normal CD5+ B lymphocyte.

PMID- 7516028
TI  - Enhanced B-lymphocyte expression of IL-2R alpha associated with T lymphocytosis
      in BLV-infected persistently lymphocytotic cows.
AB  - Peripheral blood lymphocytes from bovine leukemia virus (BLV)-negative and BLV
      infected, aleukemic cows with persistent lymphocytosis were evaluated for
      expression of B and T lymphocyte subset-specific molecules and co-expression of
      the interleukin-2 receptor alpha (IL-2R alpha) molecule. Results demonstrate
      enhanced mitogen-induced expression of the IL-2R alpha molecule on B lymphocytes
      from BLV-infected, lymphocytotic cows. Lymphocyte subset analyses further
      demonstrate that BLV-infected, lymphocytotic cows are not only characterized by
      sustained elevations in CD5+ B lymphocytes, but also show significantly elevated
      numbers of CD3+, CD4+, and CD8+ T lymphocytes. These results provide evidence
      suggesting that B lymphocytes from BLV-infected, lymphocytotic cows are more
      sensitive to activation signals and up-regulation of the IL-2 signaling pathway
      than lymphocytes from clinically normal BLV-free cows, and that T lymphocytes may
      be involved in the aberrant regulatory pathways underlying BLV-induced persistent
      B lymphocytosis.

PMID- 7516027
TI  - Antiproliferative activity of cyclopentenone prostaglandins in early HTLV-1
      infection is independent of IL-2 and is associated with HSP70 induction.
AB  - Cyclopentenone prostaglandins PGA1 and PGJ2 can inhibit the growth of HTLV-1
      infected cord blood-derived human mononuclear cells (CBMC), both after acute
      infection and in chronically infected, immortalized cells. When CBMC were exposed
      to HTLV-1 infection by coculturing with lethally irradiated, virus-donor
      allogeneic MT-2 cells, they underwent a proliferative response, that peaked
      within the first week and then declined. PG treatment did not inhibit the initial
      proliferation (day 4) of cocultured CBMC, while multiple treatments with PGA1 and
      more efficiently with PGJ2, suppressed the late cell proliferation (from day 8
      onward). The pharmacological effects of PGA1 and PGJ2 were reversible and
      therefore multiple treatments were required to maintain their antiproliferative
      activity. Increasing concentrations (20, 40, 80 IU/ml) of recombinant IL-2 did
      not affect the virus-associated proliferative response of CBMC, and exogenous IL
      2 did not revert the antiproliferative effect of both PGs. Arrest of
      proliferation in cocultured CBMC occurred concomitantly with expression of high
      levels of HSP70 in the cells. In fact, though HSP70 expression was induced early
      (day 5) after exposure to HTLV-1, its expression was further increased after
      multiple PG treatments and high levels were found when the antiproliferative
      effect of PGs became manifest. Since HSP70 protein family is involved in the
      control of cell cycle as well as in antigen processing and presentation during
      the immune response against tumor cells and pathogens, the persistent expression
      of this protein in PG-treated cocultures suggested that, beside inhibiting the
      growth of virus-infected cells, HSP70 expression might play a role in modulating
      the immune function of CBMC. However, unlike in most virus infection models, in
      which cyclopentenone PGs exert clear antiviral effects by inhibiting the
      synthesis and maturation of virus proteins, no antiviral activity was found in
      this model of infection. This strongly suggests that the main effect of these PGs
      against HTLV-1 infected cells consists in inhibiting proliferation in vitro
      without affecting viral expression.

PMID- 7516030
TI  - P-glycoprotein expression as unfavorable prognostic factor in acute myeloid
      leukemia.
AB  - In order to further define the role of the MDR1 gene in acute myeloid leukemia
      (AML), we determined the association between the presence of P-glycoprotein on
      leukemic cells and the efficacy of therapy in patients with AML.
      Immunocytochemistry with monoclonal antibody C219 was performed to demonstrate
      the presence of P-glycoprotein. Positive staining ranged from 0 to 60% of the
      leukemic cells. For further analysis, patients were assigned into groups with 0
      5% staining cells (group 1, n = 33) and with > 5% staining cells (group 2, n =
      19). The complete remission rate of induction chemotherapy was 76% for group 1
      but only 32% for group 2 (p = 0.002). The median duration of overall survival was
      19 months for patients in group 1 as compared to 3 months for patients in group 2
      (p = 0.007). The data indicate that P-glycoprotein expression is associated with
      an unfavorable prognosis in patients with AML.

PMID- 7516029
TI  - Significantly lower P-glycoprotein expression in acute promyelocytic leukemia
      than in other types of acute myeloid leukemia: immunological, molecular and
      functional analyses.
AB  - Expression of P-glycoprotein (Pgp), the product of the multidrug resistance
      (MDR1) gene, detected by flow cytometric analysis of the binding of antibody
      4E3.16, was found on significantly fewer leukemic cells in 35 adult patients with
      de novo acute promyelocytic leukemia (APL) (mean 14.8%, median 7%) than in 184
      patients with non-APL acute myeloid leukemia (AML) at diagnosis (mean 28.3%,
      median 18%) (p = 0.0038). APL was diagnosed based on morphology, the detection of
      t(15;17) and of the chimeric fusion transcript PML/RAR alpha by PCR. To further
      substantiate low MDR1 expression in APL, we studied cells from 11 APL patients at
      the molecular and functional level in comparison to 48 non-APL cases. The
      diagnosis of APL was associated with the absence of Pgp function by the rhodamine
      efflux assay (p = 0.0001). Furthermore, MDR1-specific transcript levels,
      determined by quantitative PCR with two distinct sets of primers, were
      significantly lower in mononuclear cells from the APL than the other AML cases (p
      = 0.013). The frequency of leukemic cells positive for CD34, an antigen
      presumably associated with Pgp expression in AML, was significantly lower in APL
      than other AMLs (p = 0.0001). In contrast to non-APL leukemias, those few cases
      of CD34 strongly positive APL neither expressed Pgp nor contained significant
      MDR1 transcript levels. Low expression of Pgp by APL cells may provide the
      biologic basis for the high sensitivity of this leukemia subtype to
      chemotherapeutic agents in vivo.

PMID- 7516031
TI  - Flow cytometric analysis of glutathione-S-transferase-pi in acute leukemia.
AB  - Increased expression of glutathione-S-transferase isoenzyme pi (GST-pi) may
      account for drug resistance and treatment failure in hematologic malignancies
      when alkylating agents like cyclophosphamide, chlorambucil, busulfan and
      melphalan, or doxorubicin are used. We have studied the expression of GST-pi in
      peripheral blood lymphocytes of healthy blood donors. In peripheral and bone
      marrow lymphocytes/blasts of patients with other diseases than hematologic
      malignancies, and of patients with acute leukemia by using flow cytometry. We
      studied bone marrow cells of 35 patients diagnosed as having acute leukemia at
      initial presentation, 16 patients in the refractory stage, 20 in morphological
      remission and 15 controls. None of the samples obtained in remission contained
      more GST-pi-positive cells than the controls, whereas 51% of the samples obtained
      at diagnosis and 56% of those obtained in the refractory stage were GST-pi
      positive. The mean proportion of GST-pi-positive cells in the lymphocyte/blast
      cell gate of bone marrow cells of controls was 2.6% and of patients with acute
      leukemia studied at diagnosis 16.6%, respectively. We analyzed the samples also
      for P-glycoprotein expression. There was a significant positive association
      between GST-pi and P-glycoprotein expression in acute leukemia.

PMID- 7516032
TI  - Expression of the multidrug resistance P-glycoprotein and its relationship to
      hematological characteristics and response to treatment in myelodysplastic
      syndromes.
AB  - Expression of P-glycoprotein (PGP), the product of the multi-drug resistance mdr1
      gene was studied by immunocytochemistry on bone marrow slides using JSB1
      monoclonal antibody and the alkaline phosphatase-antialkaline phosphatase (APAAP)
      and avidin-biotin-peroxidase (ABC) techniques in 82 cases of untreated
      myelodysplastic syndromes (MDS), of whom ten had evolved to AML (MDS-AML). The
      relationship between PGP expression, myeloperoxidase activity and immunophenotype
      of blast cells, karyotype and outcome was also analyzed. PGP expression was found
      in the blasts of 34 of the 82 patients (41%), the majority of blasts being
      stained in positive cases. PGP positivity was rare in 'low risk' MDS (RA and
      RARS: 2/12 cases) as opposed to 'high risk' MDS (RAEB, RAEB-T, CMML: 25/60 cases)
      and MDS-AML (7/10 cases) (p = 0.04). PGP expression was positively correlated to
      the presence of myeloperoxidase activity in less than 3% of blasts (p = 0.025),
      and CD34 antigen expression (p = 0.04), whereas CD33 antigen expression had
      borderline significance (p = 0.07), demonstrating that PGP expression
      predominated in blasts with an immature phenotype. An abnormal karyotype, and
      especially the presence of monosomy 7, was not correlated to a higher incidence
      of PGP expression, however. There was a trend for more frequent progression to
      AML and for shorter survival in PGP-positive cases, but differences with PGP
      negative cases were not significant. Twenty patients received intensive
      anthracycline-Ara-C chemotherapy and ten (50%) achieved complete response,
      including 9/13 (69%) PGP-negative cases and 1/7 (14%) PGP-positive cases (p =
      0.03). Twenty other patients were treated with low-dose Ara-C and ten (50%)
      responded (complete or partial response). PGP-positivity did not negatively
      affect response to low-dose Ara-C: 4/11 responses in PGP-negative, and 6/9
      responses in PGP-positive patients (p = 0.18). Because the treatment choice in
      advanced MDS (especially between anthracycline-Ara-C or low-dose Ara-C,
      chemotherapy) is difficult, our preliminary therapeutic results suggest that the
      analysis of PGP expression could have practical importance in MDS. These findings
      however, will have to be confirmed on larger numbers of patients. Clinical trials
      using drugs potentially reverting mdr, activity could also be warranted in MDS.

PMID- 7516033
TI  - [Long-term evolution of immunologic and thyroid function in Graves disease
      according different therapeutic options].
AB  - BACKGROUND: A prospective study was carried out to compare the evolution of
      thyroid hormones, thyroglobulin (Tg) and immunoglobulins inhibiting the binding
      of thyrotropin to its receptor (TBII) in patients with Graves disease treated
      with antithyroid drugs, radioactive iodine and subtotal thyroidectomy. METHODS:
      Ninety-five patients with Graves disease were studied, being distributed
      according to clinical criteria: Group I (n = 35) patients treated with
      antithyroid drugs; Group II (n = 30) patients who received 131I; and Group III (n
      = 30) patients treated with subtotal thyroidectomy. The thyroid hormones, Tg,
      antithyroglobulin antibodies and TBII were determined by radioimmunoassay (RIA),
      prior to treatment, and at 1, 3, 6, 12, 24, and 36 months of follow up, except in
      those patients from Group III who were followed up to 24 months. RESULTS: The
      rate of reactivation at 12 months did not significantly differ among the three
      groups. At 24 months a higher percentage of reactivations was observed in Group I
      (42%), versus Group II (16%, p < 0.001) and Group III (13%, p < 0.005). At 36
      months reactivation was 30% in Group I, versus 5% in Group II (p < 0.01). Upon
      comparison of the TBII values among the three groups, the highest basal values
      corresponded to Group III with significant differences being found versus Group I
      (p < 0.05) and Group II (p < 0.001). TBII concentrations in the three groups
      studied remained high at 6 and 12 months with no significant differences being
      observed. Negativization was shown in the TBII at 24 months in Group II with a
      significant difference being seen versus Group I and III. At 36 months
      negativization was seen in the TBII in Group I with significant differences with
      respect to Group II. CONCLUSIONS: The rate of reactivation following antithyroid
      treatment is greater to that obtained in groups treated with iodine or surgery.
      The earliest negativization of TBII was obtained with radioiodine.

PMID- 7516034
TI  - [Prevalence of hepatitis C virus antibodies in homosexual men].

PMID- 7516035
TI  - Flowcytometric analysis of the effect of berberine on the expression of
      glucocorticoid receptors in human hepatoma HepG2 cells.
AB  - Berberine is an alkaloid found in many plants, including the Coptis chinensis and
      Arcangelisia flava. Berberine has been reported to have cytostatic effect on
      tumor growth. Previously, we have found that the level of glucocorticoid
      receptors (GR) was significantly higher in hepatoma than in adjacent liver
      tissues. Using human HepG2 hepatoma cells, we have found that GR were expressed
      not only in G0-G1 phases, but also in S and G2+M phases. The objective of the
      present study was to examine the effect of berberine on the expression of GR and
      its relation to cell cycle progression of HepG2 cells. Continuous exposure of
      HepG2 cells to various concentrations (1-50 microM) of berberine resulted in
      growth inhibition in a dose dependent manner. The viability of berberine-treated
      HepG2 cells was greater than 90% in all treatment groups. Flowcytometric analysis
      of berberine-treated HepG2 cells showed that the S phase fraction was
      significantly reduced. GR levels were higher in berberine-treated HepG2 cells
      than in vehicle (DMSO)-treated cells. In addition, the secretion of alpha
      fetoprotein by HepG2 cells was inhibited by berberine. Finally, the berberine
      induced cell growth arrest was partially reversible in HepG2 cells.

PMID- 7516036
TI  - Effect of beta-carotene on clastogenic effects of mitomycin C, methyl
      methanesulphonate and bleomycin in Chinese hamster ovary cells.
AB  - The effect of beta-carotene on the frequencies of micronuclei (MN) induced in
      cytochalasin blocked binucleated Chinese hamster ovary cells (CHO) by a
      bifunctional alkylating agent mitomycin C (MMC), a monofunctional alkylating
      agent methyl methanesulphonate (MMS) and a radio-mimetic agent bleomycin (BLEO)
      was investigated. Four different modes of application of the combination of
      clastogens and beta-carotene were examined (pre-treatment, simultaneous
      treatment, pre- +simultaneous treatment and post-treatment). The results obtained
      showed no effect of beta-carotene on the frequencies of MN induced by MMS, a
      slight but not statistically significant reduction of MMC-induced MN only when
      beta-carotene was used in low concentrations (0.25 and 0.5 microM) and a
      potentiation of the clastogenicity of bleomycin by beta-carotene in three of the
      treatment regimes utilized, post-treatment being ineffective. On the basis of
      these results it can be concluded that the effect of beta-carotene on
      clastogenesis induced by chemicals depends on the type and mechanism of action of
      the clastogen used as well as the treatment protocol employed.

PMID- 7516037
TI  - Regulating physician-assisted death.

PMID- 7516038
TI  - Cytotoxic T-cell memory without antigen.
AB  - Memory is a hallmark of the immune system and ever since its recognition there
      has been considerable interest in understanding how immunity is maintained. The
      current model is that long-term memory is dependent on persistent antigenic
      stimulation. We report here results that challenge this view and provide evidence
      that antigen is not essential for the maintenance of CD8+ T-cell memory. We show
      that memory CD8+ cytotoxic T lymphocytes persist indefinitely in the absence of
      priming antigen, retain the memory phenotype (CD44hi), and provide protection
      against virus challenge. These findings suggest a re-evaluation of our current
      thinking on mechanisms involved in maintaining immunity and have implications
      towards designing effective vaccination strategies.

PMID- 7516039
TI  - Virus-specific CD8+ T-cell memory determined by clonal burst size.
AB  - Although some viruses, particularly the herpes viruses, may never be eliminated
      from the body, others like influenza A, regularly reinfect humans and boost
      waning crossreactive CD8+ T-cell immunity. Prolonged T-cell memory is found for
      viruses that are unlikely to be re-encountered and which do not persist in the
      host genome, indicating that CD8+ T-cell memory might be independent of continued
      (or sporadic) antigenic exposure. A feature of virus-specific CD8+ T-cell memory
      is that antigen-specific cytotoxic T-lymphocyte precursors (CTLp) are greatly
      increased and remain high throughout life. The idea that persistence of the
      inducing antigen is essential is based on experiments in which adoptively
      transferred CD8+ memory T cells could not be detected for more than a few weeks
      in naive recipient mice without secondary challenge. Here we show that
      restimulation of such chimaeric mice with an inducing Sendai virus antigen
      increases the clonal burst size more than 7-fold within 8 days, making memory
      CTLp easier to detect in the longer term. We find that Sendai-virus-specific CTLp
      are maintained for > 250 days in irradiated uninfected recipients, including
      reconstituted beta 2-microglobulin-/- mice. To determine whether a source of
      viral peptide can persist after primary infection, we gave Sendai-virus-specific
      Thy1.1+ memory spleen cells to naive mice that had been minimally depleted of
      Thy1.2+ T cells, or to comparable recipients that had recovered from infection
      with Sendai virus or influenza virus. Although antibody against Sendai virus was
      never found in the naive recipients, Sendai-virus-specific CD8+ memory T cells
      were maintained equally well in each case for > 100 days after cell transfer. We
      find no evidence for persisting depots of viral protein that might feed into the
      endogenous processing pathway and maintain virus-specific CD8+ T-cell memory.

PMID- 7516041
TI  - Analysis of plasma and hematoma lipids related to choline glycerophospholipid in
      patients with chronic subdural hematoma.
AB  - The levels of platelet-activating factor (PAF) and lipid metabolites related to
      choline glycerophospholipid were measured in the plasma and hematoma samples
      obtained from patients with chronic subdural hematoma. The ratio of lyso-choline
      glycerophospholipids (lysoPC) to choline glycerophospholipids (PC) in hematoma
      correlated with the interval between the onset of symptoms and surgery. PC and
      lysoPC fatty acyl moieties in plasma and hematoma were essentially similar. These
      results suggest that the lysoPC to PC ratio in hematoma can determine the age of
      the chronic subdural hematoma, and that the origin of hematoma may be circulating
      blood. The levels of PAF in the plasma of chronic subdural hematoma patients were
      significantly greater than in healthy volunteers. PAF may be involved in the
      enlargement of chronic subdural hematoma.

PMID- 7516042
TI  - Immunophenotypic analysis of primary malignant lymphoma of the brain.
AB  - The immunophenotypes in three cases of primary malignant lymphomas of the brain
      were analyzed by flow cytometry using a panel of monoclonal antibodies. In all
      three cases the immunophenotypes were CD10 negative, CD19 positive, and CD20
      positive, and in two cases human leukocyte antigen (HLA)-DR positive. CD20 showed
      high positivity (80-97%), while CD19 revealed low positivity (30-50%). These
      neoplastic cells apparently became malignant at the B-cell differentiation stage,
      when they expressed both CD19 and CD20. Differentiation continued until CD19 was
      no longer expressed, when further differentiation stopped between the last stage
      of B-cell differentiation and the early stage of plasma cell formation (Case 3
      was CD38 positive). Case 1 was immunoblastic type lymphoma and the cells were
      both surface immunoglobulin and HLA-DR negative. At least 40% of Case 2 cells
      showed both B-cell and T-cell markers. Immunophenotypic study can help determine
      the cell lineage, clonality, and stage of differentiation of lymphoid neoplasms.

PMID- 7516040
TI  - The isoquinoline derivative LOE 908 selectively blocks vasopressin-activated
      nonselective cation currents in A7r5 aortic smooth muscle cells.
AB  - The effect of (R,S)-(3,4-dihydro 6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl- N,N
      di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908), a cation channel
      blocker in HL-60 promyeloblasts, was studied in the A7r5 smooth muscle cell line
      from rat thoracic aorta, using the whole-cell patch-clamp technique. At a holding
      potential of -60 mV, application of vasopressin induced a nonselective cation
      conductance in voltage-clamped A7r5 cells. The current-voltage relation was
      linear, and currents reversed close to 0 mV regardless of the chloride gradient.
      The activation of the nonselective cation conductance by vasopressin was not
      affected by dialysing cells with Ca(2+)-free internal solution. LOE 908 blocked
      this current in a concentration-dependent manner with an IC50 of 560 nM, whereas
      dihydropyridine-sensitive Ba2+ current through voltage-dependent Ca2+ channels
      was blocked with an IC50 of 28 microM. Another organic blocker of receptor
      mediated Ca2+ entry, 1-beta-[3-(4-methoxyphenyl)-propoxy]-4-methoxyphenethyl-1H
      imidazole hydrochloride (SK&F 96365), blocked both, the vasopressin-induced
      nonselective conductance and the voltage-activated Ba2+ current with similar IC50
      values of 13 microM and 8 microM, respectively. The rank order of potency of
      inorganic blockers on the vasopressin-induced inward current was Gd3+ > La3+ >
      Cd2+. Vasopressin-induced non-selective cation current was also observed in
      pertussis toxin-pretreated A7r5 cells but was completely abolished after infusion
      of the GDP analogue, guanosine 5'-O-[3-thio]diphosphate, from the patch pipette.
      Furthermore, vasopressin induced a transient outward current, suggesting a Ca(2+)
      activated K(+)-current, which overlapped with the nonselective cation
      conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516043
TI  - Improved bioassay for the detection of transforming growth factor-beta 1 and beta
      2 in malignant gliomas.
AB  - Growth inhibition assays using radioisotope or dye are used to detect
      transforming growth factor-beta (TGF-beta). Here, we describe a modified bioassay
      using crystal violet for the quantitative detection of TGF-beta 1 and TGF-beta 2.
      The procedure is based on staining Mv1Lu mink lung epithelial cells with crystal
      violet, followed by measurement of the absorbance at 570 nm in individual wells
      of a 96-well microtiter plate. The number of Mv1Lu cells correlated with the
      eluted dye intensity. The sensitivity of the bioassay to recombinant TGF-beta 1
      and TGF-beta 2 increased approximately twofold by using only 500 Mv1Lu cells in
      microtiter wells. The bioassay was used to measure TGF-beta activity in the
      culture supernatant from glioblastoma cells. Culture supernatants were untreated
      or acid-activated to quantify the active or total TGF-beta, and neutralized with
      anti-TGF-beta 1 and/or anti-TGF-beta 2 antibody to measure the activity. Both TGF
      beta 1 and TGF-beta 2 were detected in the untreated and acid-activated
      supernatants, and the amounts were calculated by extrapolating from the known
      recombinant TGF-beta 1 or TGF-beta 2 dilution curve. Our results show that the
      modified bioassay using crystal violet can measure the levels of TGF-beta 1 and
      TGF-beta 2 in culture supernatants from malignant glioma cells.

PMID- 7516044
TI  - Microsurgical anatomy of the cavernous sinus.
AB  - The cavernous sinuses of 50 adult cadavers were examined to investigate the
      relationships of the blood vessels and cranial nerves, important structures
      during surgery in this sinus. The first and second divisions of the fifth cranial
      nerve were embedded in the deep dural layer of the cavernous sinus and were
      supplied by the two main branches of the intracavernous carotid artery. The
      meningohypophyseal artery supplied the sixth cranial nerve in Dorello's canal and
      the third and fourth cranial nerves where they entered the dura. The
      inferolateral trunk supplied the third, fourth, fifth, and sixth cranial nerves.
      The size of the meningohypophyseal artery was usually inversely proportional to
      the size of the inferolateral trunk. The capsular artery did not supply the
      cranial nerves. The cavernous sinus can be approached through various routes: a)
      superior, through the anteromedial or medial triangle; b) lateral, through the
      paramedial, Parkinson's, anterolateral, and lateral triangles; c) inferior,
      through the posterolateral and posteromedial triangles; and d) from the
      inferomedial walls. The choice of surgical approach depends mainly on the
      location of the lesion to be treated.

PMID- 7516046
TI  - Fatal subarachnoid hemorrhage due to ruptured infundibular widening of the
      posterior communicating artery--case report.
AB  - A 57-year-old male suffered a fatal subarachnoid hemorrhage due to ruptured
      infundibular widening of the internal carotid-posterior communicating artery
      junction, confirmed by autopsy. Infundibular widening is a preaneurysmal or
      aneurysmal lesion and indicates angiographic follow-up and control of blood
      pressure when identified.

PMID- 7516045
TI  - Serial transcranial Doppler flow velocity and cerebral blood flow measurements
      for evaluation of cerebral vasospasm after subarachnoid hemorrhage.
AB  - Serial transcranial Doppler (TCD) and cerebral blood flow (CBF) examinations were
      performed in 73 patients with subarachnoid hemorrhage (SAH) due to ruptured
      intracranial aneurysm to evaluate cerebral vasospasm. Twenty-six (35.6%) of the
      73 patients developed ischemic neurological symptoms associated with cerebral
      vasospasm, which were reversible in all except four patients (5.5%) who
      demonstrated low-density areas associated with vasospasm on computed tomographic
      scans. In general, the flow velocities in the middle cerebral arteries began to
      increase soon after onset of SAH, reaching the maximum between days 8 and 10,
      subsequently decreasing gradually. There was no significant difference in the
      highest value and the time course of flow velocities between symptomatic
      vasospasm and asymptomatic vasospasm patients. Patients with symptomatic
      vasospasm demonstrated two typical time courses of flow velocities: rapid
      increases in flow velocities that preceded the clinical manifestations of
      vasospasm (16 patients, 61.5%), and no rapid increases in flow velocities despite
      the presence of ischemic symptoms (10 patients, 38.5%). In the latter, angiograms
      demonstrated vasospasm in segments distal to those evaluated by TCD examination.
      These results showed that the degree of cerebral vasospasm cannot be assessed
      only by the absolute flow velocities. CBF was measured two to 10 (mean 4.7) times
      within 3 weeks of SAH using the 133Xe intravenous injection method. The CBF value
      remained stable even during the period of major risk of vasospasm. However, the
      CBF was significantly lower in patients with symptomatic vasospasm on days 8, 9,
      10, 13, 14, and 15, when compared with patients without symptomatic
      vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516048
TI  - Metastatic leiomyosarcoma of the skull--case report.
AB  - A 65-year-old female presented with a rare intestinal leiomyosarcoma metastasis
      to the skull manifesting as a mass beneath the scalp. She was free of
      neurological and physical symptoms on admission. The tumor was totally removed
      with normal surrounding bone and dura. The histological diagnosis was
      leiomyosarcoma. Ultrastructural and immunohistochemical studies demonstrated the
      smooth muscle origin of the tumor. Such patients in good physical condition
      should be immediately treated surgically to achieve the best chance of survival.

PMID- 7516049
TI  - Choroid plexus metastasis from gastric cancer--case report.
AB  - A 64-year-old male presented with a unique choroid plexus metastasis from gastric
      cancer. Computed tomography and magnetic resonance imaging demonstrated a
      moderately enhanced mass in the lateral ventricle. The tumor was totally removed
      and histological examination revealed adenocarcinoma. Systemic investigation
      revealed gastric cancer. The differential diagnosis for intraventricular masses
      should include the possibility of metastasis from unidentified primary lesions.

PMID- 7516047
TI  - Meningioma associated with chronic subdural hematoma and meningothelial cell
      cluster within the hematoma capsule--case report.
AB  - A 47-year-old female presented with an unusual association of convexity
      meningioma with chronic subdural hematoma, manifesting as headache and left
      hemiparesis 10 days before admission. Computed tomography showed an isodense
      right frontal tumor with significant enhancement postcontrast and a hypodense
      subdural hematoma in the right frontotemporal area. Craniotomy exposed an
      extracerebral tumor facing a liquefied subdural hematoma encapsulated by outer
      and inner membranes. The hematoma was evacuated and the tumor was totally
      removed. Histological examination revealed a meningothelial meningioma with
      hemangiopericytic components. Microscopic examination of the hematoma capsule
      revealed a cluster of meningothelial cells in the outer membrane.

PMID- 7516050
TI  - Improved provocative test for the embolization of arteriovenous malformations-
      technical note.
AB  - A modified provocative test to assess the safety of embolization of cerebral and
      spinal arteriovenous malformations is described. The modified test uses
      successive amobarbital and lidocaine injections to elicit any possible
      neurological deficit, both mixed with radiopaque material to visualize the
      distribution of the anesthetic in the vessels. The modified provocative test
      caused no false negative results in 11 patients tested, compared to six of 27
      patients with the unmodified method.

PMID- 7516051
TI  - The Purkinje cell in olivopontocerebellar atrophy. A Golgi and immunocytochemical
      study.
AB  - Purkinje cells were examined in three familial cases of olivopontocerebellar
      atrophy (OPCA) by means of the Golgi method, and neurofilament and calcium
      binding protein immunocytochemistry. Reduced dendritic arborizations, as seen
      with different techniques, early formation of axonal spheroids, and abnormal
      accumulation of phosphorylated neurofilament epitopes in dendrites, somata and
      axonal spheroids, together with limited formation of proximal spine-like
      protrusions were the main changes in Purkinje cells. These lesions are unlikely
      to be the consequence of anterograde degeneration secondary to olivary atrophy,
      as postulated by some investigators, but probably represent primary damage to
      Purkinje cells in patients with OPCA. Reduced dendritic arborizations result in a
      decrease of receptor sites for parallel fibres and deprive granule cells of their
      main targets. Abnormal accumulation of neurofilaments in somata, dendrites and
      axonal spheroids may contribute to an abnormal transport and may impair protein
      turnover in the distal regions of Purkinje cells.

PMID- 7516052
TI  - Co-incidence of Guillain-Barre syndrome and spinal cord compression in non
      Hodgkin lymphoma.
AB  - Extradural, radicular and spinal cord compressions are severe neurological
      complications of lymphomas. Less frequently, involvement of the peripheral
      nervous system, polymyositis, myasthenia gravis and Guillain-Barre syndrome (GBS)
      occur. We report a patient with GBS along with a lymphoma of the spinal
      extradural space where at the beginning the features of GBS outweighed the
      symptomatology of the extradural spinal mass.

PMID- 7516053
TI  - Neurotensin modulates cholinergic and noncholinergic neurotransmission in guinea
      pig main bronchi in vitro.
AB  - Guinea-pig main bronchi were stimulated transmurally in vitro by electrical field
      stimulation in the presence of indomethacin 10(-6) M, propranolol 10(-6) M and
      phosphoramidon 10(-5) M. Two contractile neurogenic responses were successively
      observed. The second noncholinergic contraction was concentration dependently
      inhibited or abolished by neurotensin whereas the first cholinergic contraction
      was only partially inhibited. SR 48692, a novel antagonist of neurotensin
      receptors, reduced the inhibition induced by neurotensin (pKB = 9.75) whereas
      levocabastine, an antagonist of low-affinity neurotensin receptors, did not
      significantly modify the inhibitory effects of neurotensin on both neurally
      mediated contractions. These results demonstrate that neurotensin exerts an
      inhibitory effect on neurotransmission in guinea-pig airways. Furthermore, the
      present study shows that the newly developed neurotensin receptors antagonist, SR
      48692, is a potent inhibitor of the neurotensin inhibitory effects on cholinergic
      and noncholinergic contractions induced by electrical field stimulation of the
      guinea-pig isolated main bronchus.

PMID- 7516055
TI  - Anti-MAG antibodies: major effects of antigen purity and antibody cross
      reactivity on ELISA results and clinical correlation.
AB  - There is controversy regarding the relationship of polyneuropathy syndromes to
      the presence of serum antibody binding to myelin-associated glycoprotein (MAG).
      Using standard ELISA methodology, we identified 74 sera that appeared to have
      high titers of IgM binding to MAG and found that only 34% of these sera stained
      MAG using Western blot methodology. Follow-up studies showed that two factors
      greatly influence concordance between ELISA and Western blot testing for anti-MAG
      antibodies. Sera with high titers of binding to both MAG and histone H3
      identified by ELISA rarely stain MAG on Western blot. In addition, sera analyzed
      by ELISA often bind to impurities in the semipure MAG that is frequently used in
      ELISA assays. Further purifications to separate MAG from other contaminants
      improved concordance between ELISA and Western blot results to 85% to 90% in a
      retrospective analysis, as well as in a prospective study of 49 additional sera.
      Patients with a polyneuropathy and serum IgM binding to MAG preparations by ELISA
      but not by Western blot methodology had several different clinical syndromes,
      including gait disorders and asymmetric motor neuropathies. Patients with IgM
      binding to MAG by both assay methods usually had a distal, sensory-motor,
      symmetric polyneuropathy with some features of demyelination on electrodiagnostic
      testing.

PMID- 7516054
TI  - Expression of HIV-1 and interleukin-6 in lumbosacral dorsal root ganglia of
      patients with AIDS.
AB  - We examined the immunopathology and the expression of human immunodeficiency
      virus type 1 (HIV-1) in lumbosacral dorsal root ganglia (DRGs) from 16 patients
      with acquired immunodeficiency syndrome (AIDS) and 10 HIV-1-seronegative
      controls. Using in situ hybridization, we detected HIV-1 RNA in a few
      perivascular cells in DRGs from five of 16 AIDS patients (31%). In addition,
      using polymerase chain reaction, we detected HIV-1 DNA more frequently in DRGs
      from four of five AIDS patients (80%) examined. We detected interleukin-6 (IL-6)
      immunoreactivity in endothelial cells in DRGs from seven of 16 AIDS patients
      (44%) but from none of 10 HIV-1-seronegative controls (0%). We found more nodules
      of Nageotte, CD8+ T lymphocytes, and intercellular adhesion molecule-1 (ICAM-1)
      positive endothelial cells and mononuclear cells in DRGs from AIDS patients than
      in DRGs from controls. Increased numbers of nodules of Nageotte in DRGs of AIDS
      patients were associated with detection of HIV-1 RNA by in situ hybridization and
      detection of IL-6 by immunohistochemistry. We conclude that low levels of
      replication of HIV-1, through cytotoxic T lymphocytes or expression of cytokines,
      may play a role in the subclinical degeneration of sensory neurons frequently
      observed in DRGs of AIDS patients.

PMID- 7516056
TI  - Serum levels of soluble E-selectin (ELAM-1) in immune-mediated neuropathies.
AB  - Adhesion molecules are critically involved in inflammatory responses. We studied
      serum concentrations of the soluble form of E-selectin (endothelial-leukocyte
      adhesion molecule-1, ELAM-1) in 187 patients with neuropathies of diverse
      etiology, 54 patients with other noninflammatory, nondemyelinating neurologic
      disorders, and 15 healthy controls. Serum E-selectin levels, quantitated by a two
      site enzyme-linked immunosorbent assay, were significantly increased in 126
      patients with Guillain-Barre syndrome (GBS) (mean +/- SD, 45.1 +/- 16.3 ng/ml)
      and 13 patients with vasculitic neuropathies (47.1 +/- 19.1ng/ml) compared with
      patients with other neurologic diseases (19.8 +/- 7.4 ng/ml) and healthy controls
      (21.9 +/- 8.1 ng/ml). In GBS, E-selectin levels were temporally related to
      disease activity. Cytokine-mediated upregulation of E-selectin may be important
      in homing and attachment of leukocytes to endoneurial endothelial cells. Raised E
      selectin concentrations probably reflect endothelial cell activation occurring
      early in the sequence of immunopathologic events culminating in peripheral nerve
      damage.

PMID- 7516057
TI  - Glial differentiation in medulloblastoma. Case report.
AB  - A 30-year-old man suffered for a year of a typical syndrome of cerebellar tumor.
      At suboccipital craniectomy a soft tumor infiltrating both hemispheres and
      vermis, filling up part of the IV ventricle was found. After subtotal removal of
      the neoplasm the postoperative course was poor and the patient died 5 weeks
      later. Biopsy material consisted of three types of tissue: 1. large nests of
      carrot-shaped, hyperchromatic cells, 2. fields of "halo" cells presenting myelin
      basic protein (MBP) immunoreactivity and 3. fields and scattered strongly GFAP
      positive cells. The histological and immunocytochemical pattern of the neoplasm
      indicates differentiation of the tumor into oligodendrogliomatous and
      astrocytomatous line being an uncommon example of dual glial differentiation
      capability in medulloblastoma.

PMID- 7516060
TI  - Distinct conformations of p53 are observed at different stages of keratinocyte
      differentiation.
AB  - p53 is a multifunctional protein that has been shown to inhibit the growth of
      transformed cells, arrest the cell cycle of normal cells, regulate gene
      transcription and influence cellular differentiation, apoptosis and senescence.
      This study was undertaken to determine if the expression of p53 in keratinocytes
      varied during epidermal differentiation. Fresh frozen-sections of normal human
      epidermis were subjected to immunofluorescence using a panel of anti-p53
      monoclonal antibodies. The monoclonal antibody 122 specifically stained the basal
      layer of the epidermis. No staining was observed in other cell layers of the
      epidermis using the 122 antibody. When the 240 antibody was used, p53 was only
      detected in granular layer cells. No other anti-p53 monoclonal antibody stained
      normal epidermis. Immunofluorescent analyses of cultured keratinocytes revealed
      staining patterns that correlated with the staining pattern seen in vivo.
      Immunoprecipitation assays of the cultured keratinocytes indicated that each
      monoclonal antibody, with the exception of DO-1, could only detect a fraction of
      the total p53 present in the cultures. This diversity of reactivity was presumed
      to be due to the masking and exposing of the various epitopes on p53 through the
      binding of other proteins. Finally, in cultured human keratinocytes, p53 was
      found to be a relatively stable protein with a half-life of 5 h.

PMID- 7516059
TI  - Medical decisions near the end of life.

PMID- 7516058
TI  - [Primary retroperitoneal tumors. Our experience].
AB  - Primary retroperitoneal tumors are rare (0.05-0.2% of all tumors), often
      malignant and characterized by a poor and non-specific symptomatology and by a
      late diagnosis. Complete resection is possible in only a few patients, while
      recurrence is very common. The records of 29 adult patients who underwent
      operative treatment at Surgical Oncology Institute-University of Cagliari between
      November 1973 and June 1992 were reviewed; 9 were males, 20 females, median age
      46.4 years (range 12-82). There were 4 benign tumors (13.8%) and 25 malignant
      (86.2%). Fibrosarcoma (9 cases, 31%) and liposarcoma (3 cases, 10.3%) were the
      most frequent histologic types. There were also two fibroleiomyomas,
      leiomyosarcomas, malignant fibrous histiocytomas and neuroblastomas, one case of
      fibroma, neurofibroma, rhabdomyosarcoma and schwannoma. Five sarcoma were not
      otherwise specified. Abdominal mass (25 cases, 86.2%), flank or abdominal pain
      (15 cases, 51.7%) and weight loss (8 cases, 27.6%) were most common symptoms;
      change in bowel habit and constipation (6 cases, 20.7%), fever (5 cases, 17.2%),
      urinary disorders (4 cases, 13.8%) nausea and vomiting (2 cases, 6.7%) were less
      common. Diagnosis was made by ultrasonography, computed tomography and
      traditional radiographic studies. median interval between first symptoms and
      diagnosis was 11 months. Complete surgical resection was possible in only 13
      cases (46.4%): 10 of the 25 malignant tumors (40%) and 3 of the 4 benign tumors
      (75%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516061
TI  - Tyrosine dephosphorylation of pp60c-src is stimulated by a serine/threonine
      phosphatase inhibitor.
AB  - Incubation of NIH3T3-derived c-src overexpressor cells with okadaic acid, a
      specific serine/threonine phosphatase inhibitor, stimulates pp60c-src kinase
      activity about 2-3-fold. Activation is blocked if cells are simultaneously
      treated with orthovanadate, a tyrosine phosphatase inhibitor. Furthermore,
      okadaic acid treatment induces a small decrease in Tyr 527 phosphorylation of
      wild-type pp60c-src and a large decrease in Tyr 527 phosphorylation of kinase
      defective pp60c-src(Lys 295-->Arg). These results suggest that the activation is
      mediated by okadaic acid-induced changes in tyrosine phosphorylation of pp60c-src
      involving 'cross-over' from serine/threonine to tyrosine signal transduction
      pathways. Stimulation of pp60c-src activity and Tyr 527 dephosphorylation do not
      require changes in serine/threonine phosphorylation of pp60c-src, suggesting that
      these changes result from modulation of an upstream Tyr 527 phosphatase or kinase
      which is itself regulated by altered serine/threonine phosphorylation. Since
      okadaic acid induces a pseudo-mitotic phenotype in rodent cells (K. Yamashita, H.
      Yasuda, J. Pines, K. Yasumoto, H. Nishitani, M. Ohtsubo, T. Hunter, T. Sugimura
      and T. Nishimoto, EMBO J., 9: 4331-4338, 1990), it is possible that these
      phenomena are induced by a biochemical mechanism similar to that which causes
      transient tyrosine dephosphorylation of pp60c-src during mitosis.

PMID- 7516062
TI  - The protein tyrosine kinase substrate cortactin is differentially expressed in
      murine B lymphoid tumors.
AB  - Src family protein tyrosine kinases (PTKs) actively participate in signal
      transduction during lymphocyte activation. However, little is known about the
      roles of PTKs and their substrates in lymphocyte differentiation. To identify PTK
      substrates that may be differentially expressed during B lymphopoiesis, we
      screened a panel of murine B lymphoid tumor cell lines representing various
      developmental stages using monoclonal antibodies (MAbs) specific for pp60src
      substrates. A MAb specific for cortactin, a filamentous-actin binding pp60src
      substrate, immunoprecipitated proteins from murine plasma-cytoma cell lines but
      not from pre-B cell lymphoma or B cell lymphoma cell lines. We have cloned a
      murine cortactin cDNA which encodes a member of a family of proteins
      distinguished by amino-terminal repeat domains and carboxy-terminal Src Homology
      3 domains. Two members of this family (cortactin and HS1) were differentially
      expressed in murine B lymphoid tumor cell lines; both were detected in
      plasmacytoma cell lines, however HS1 was additionally detected in pre-B lymphoma
      and B lymphoma cell lines. Cortactin RNA was detected in most murine tissues, but
      was not detected in B lymphocytes or plasma cells. We hypothesize that cortactin
      expression is associated with transformed plasma cells and not with the terminal
      differentiation of normal B lymphocytes to plasma cells.

PMID- 7516063
TI  - Molecular cloning of lsk, a carboxyl-terminal src kinase (csk) related gene,
      expressed in leukocytes.
AB  - Regulation of the activity of src-family kinases is thought to occur, in part,
      through the phosphorylation of conserved carboxyl-terminal tyrosine residues.
      Although the src-family includes several molecules with tissue or cell-type
      restricted expression, the only kinase implicated in the regulatory
      phosphorylation of these enzymes is p50csk. Herein we report the molecular
      cloning of a tissue specific p50csk-related gene. Like p50csk, the deduced
      protein sequence of this novel cDNA includes a tyrosine kinase catalytic domain,
      SH2 and SH3 domains, a short amino terminus, and no autophosphorylation or
      carboxyl-terminal tyrosine residues. Additionally, neither this novel kinase nor
      p50csk contain the amino-terminal myristoylation site characteristic of the src
      family. However, whereas csk is ubiquitously expressed, mRNA corresponding to
      this novel gene is expressed in brain, natural killer (NK) cells, and activated T
      cells but not in a variety of other tissues and cell lines. In agreement with the
      mRNA expression pattern, antiserum reactive with the predicted carboxyl-terminus
      of the cDNA recognizes a 57 kDa polypeptide in immunoblots of NK cells and PHA
      activated T cells. Because of its limited expression and high homology to p50csk,
      we named this gene lsk; leukocyte carboxyl-terminal src kinase related gene.
      Identification of a molecule like lsk suggests the existence of tissue specific
      src-regulatory pathways that function in activated lymphocytes.

PMID- 7516065
TI  - Specific detection of minus strand hepatitis A virus RNA by Tail-PCR following
      reverse transcription.

PMID- 7516066
TI  - Simple and rapid 5' and 3' extension techniques in RT-PCR.

PMID- 7516064
TI  - Removal of 3'-phosphoglycolate from DNA strand-break damage in an oligonucleotide
      substrate by recombinant human apurinic/apyrimidinic endonuclease 1.
AB  - A recombinant human AP endonuclease, HAP1, was constructed and characterized with
      respect to its ability to recognize and act upon a model double-stranded 39-mer
      oligodeoxyribonucleotide substrate containing a strand break site with 3'
      phosphoglycolate and 5'-phosphate end-group chemistries. This
      oligodeoxyribonucleotide substrate exactly duplicates the chemistry and
      configuration of a major DNA lesion produced by ionizing radiation. HAP1 was
      found to recognize the strand break, and catalyze the release of the 3'
      phosphoglycolate as free phosphoglycolic acid. The enzyme had a Vmax of 0.1
      fmole/min/pg of HAP1 protein, and a Km of 0.05 microM for the 3'-phosphoglycolate
      strand break lesion. The mechanism of catalysis was hydrolysis of the phosphate
      ester bond between the 3'-phosphoglycolate moiety and the 3'-carbon of the
      adjacent dGMP moiety within the oligonucleotide. The resulting DNA contained a 3'
      hydroxyl which supported nucleotide incorporation by E. coli DNA polymerase I
      large fragment. AP endonucleolytic activity of HAP1 was examined using an
      analogous double-stranded 39-mer oligodeoxyribonucleotide substrate, in which the
      strand break site was replaced by an apyrimidinic site. The Vmax and Km for the
      AP endonuclease reaction were 68 fmole/min/pg of HAP1 protein and 0.23 microM,
      respectively.

PMID- 7516067
TI  - RNA recovery efficiency for cultured cells and organ-derived cell suspensions.

PMID- 7516068
TI  - Natural course of human benign prostatic hyperplasia with relation to urinary
      disturbance.
AB  - To examine the natural course of human benign prostatic hyperplasia (BPH), cases
      in health care examination with or without slight urinary symptoms were examined
      by echography. In comparison with these cases, the size of the prostate was
      examined in patients who received prostatectomy. Prostatic sizes of health care
      cases varied widely along with increasing age, but could be divided into two
      groups: increasing or no-change. According to serial determinations of prostatic
      sizes in the increasing group, the annual growth rate of the prostate was
      calculated as 1.65 +/- 1.13 and 0.85 +/- 0.44 g in men < 65 years old and in men
      > or = 65 years old, respectively. Distribution of prostatic sizes as a function
      of age in health care cases was similar to that in operated patients, showing
      that the size was not correlated with urinary symptoms or surgical indication.
      Since uroflow rates decreased along with increasing age in the no-change group of
      operated patients, aging was a factor in deterioration of uroflow. Between the
      increasing and the no-change groups in health care cases, differences were found
      in total cholesterol and neutral fat in serum, in addition to gamma
      seminoprotein; the latter may be due to differences in the size of the prostate.
      In conclusion, natural course of the prostatic hyperplasia is separated into two
      groups, increasing and no-change. Occurrence of urinary symptoms does not simply
      relate to an increase in prostatic weight but, at least in part, to the aging
      process.

PMID- 7516069
TI  - Nuclear shape and prognosis following orchiectomy in stage D2 prostate cancer.
AB  - In this study, we have examined whether tumor grade and morphometric nuclear
      features can predict the outcome of treatment by orchiectomy in patients with
      stage D2 prostate cancer. Two outcome groups based on duration of survival
      postorchiectomy were examined, a bad outcome group of 63 patients who died from
      prostate cancer within 12 months and a good outcome group of 34 patients who
      survived beyond 5 years. Tumors were histologically classified as well (17%),
      moderate (17%), or poorly differentiated (66%). Tumor grade and patient outcome
      were significantly associated (Mann-Whitney test; P < 0.005), with 76% of poorly
      differentiated tumors in the bad outcome group, and 65% of well-differentiated
      tumors in the good outcome group. Using discriminant function analysis, tumor
      grade correctly predicted outcome in 70% of cases. A statistically significant
      difference was also detected in nuclear shape values between the two outcome
      groups (P < 0.05) and histological grades (P < 0.05). Using discriminant function
      analysis, 51% of cases were correctly classified into outcome groups using
      nuclear shape factors, a figure which rose to 65% when all nuclear morphometric
      features were used. This demonstrates that nuclear morphometric features are of
      no clinical value in predicting the outcome of treatment in stage D2 disease.
      Furthermore, these evaluations cannot select patients who might be spared
      orchiectomy on the basis of a predicted poor response. However, nuclear shape and
      variance measurements of benign glandular epithelial cells within cancerous
      prostates were significantly different from those of malignant cells (P < 0.005).
      We conclude that, while video image analysis of prostatic nuclear shape can
      reliably discriminate between benign and malignant cells, nuclear morphometric
      features are of minimal prognostic value in men with stage D2 prostate cancer
      treated by androgen ablation.

PMID- 7516070
TI  - Cathepsin D cytosolic assay and immunohistochemical quantification in human
      prostate tumors.
AB  - We quantified cathepsin D by immunoradiometric assay (IRMA) and quantitative
      immunohistochemistry in fifteen human prostate cancers, seventeen BPH, and nine
      normal prostates. The cytosolic cathepsin D concentration was higher in prostatic
      carcinoma (mean: 31.5 pmol/mg cytosol proteins; range: 10.2-66.2) than in normal
      prostate (16.0 pmol/mg cytosol proteins; 7.2-25.5; P = 0.01). Prostatic
      hyperplasia showed intermediate values (20.2 pmol/mg cytosol proteins; 7.6-33.9).
      Immunostaining of cathepsin D and prostatic acid phosphatase on serial frozen
      sections of prostate tissues was only observed in glandular epithelial cells.
      Immunostaining was quantified by computer-assisted image analysis as an
      quantitative immuno-cytochemical score (QIC score) expressed in arbitrary units
      (A.U.). QIC scores for cathepsin D were dispersed and had a tendency to be higher
      in benign prostatic hyperplasia (mean: 178.3 A.U.; range: 95-297) compared to
      normal prostate (85.2 A.U.; 2-173 P < 0.01) and prostatic carcinoma (90.0 A.U.;
      21-179 P = 0.0002). Prostatic cathepsin D levels in cytosols or immunostaining
      sections were independent of other clinicobiological parameters.

PMID- 7516072
TI  - [Mechanism of HIV-1 reverse transcription initiation].

PMID- 7516071
TI  - Evaluation of a new tumor marker for cytokeratin 8 and 18 fragments in healthy
      individuals and prostate cancer patients.
AB  - The serological results from apparently healthy individuals and prostate cancer
      patients were evaluated with a new assay called TPAcyk ELISA. This assay has a
      biochemical specificity for fragments of cytokeratins 8 and 18, and exhibits a
      low within- and between-assay imprecision. The data indicate a significant
      difference between the results of males and females, but no significant age
      dependent relation was found. The cut-off value (95% specificity) for healthy
      individuals was estimated to be 1.27 ng/mL (n = 190) for males and 0.95 ng/mL (n
      = 81) for females. When using a cut-off value of 1.27 ng/mL, we found a
      sensitivity for prostate cancer patients with T2-3 N0M0 of about 20%. For
      patients with metastatic disease, a sensitivity of 75% was found. A higher
      sensitivity was obtained with patient sera analyzed with PSA than with TPAcyk,
      particularly in patients with early stages of the disease. We conclude that the
      results from this new TPAcyk assay were significantly elevated in patients
      initially diagnosed with poorly differentiated tumors, that patients with
      localized tumors exhibited low concentrations, and that patients with metastatic
      disease showed, on average, 8 times higher concentrations than patients with
      localized disease. The combination of the TPAcyk and PSA results increased the
      sensitivity for prostate cancer, particularly in patients with metastatic
      disease.

PMID- 7516073
TI  - [Transcription of chemically modified DNA].

PMID- 7516075
TI  - Hurricane growth of malignant trophoblastic teratoma.
AB  - The case history of a 27 year old male ex-intravenous drug user who presented
      with haemoptysis and indistinct lung shadowing is reviewed. During a 3 week
      period of investigation his lung shadowing increased dramatically and it became
      apparent that he had metastases from chorionic gonadotropin-producing testis
      cancer which had undergone spontaneous regression of the primary tumour.
      Unfortunately by the time he was referred for treatment he was in respiratory
      failure and died 48 hours after treatment started. The critical importance of the
      urinary pregnancy test (available in most casualty departments to diagnose
      ectopic pregnancy) in accelerating diagnosis and treatment of such a case is
      highlighted.

PMID- 7516076
TI  - Current approaches to sinusitis.

PMID- 7516074
TI  - Palliative medicine.

PMID- 7516077
TI  - Expression of adhesion molecules by endovascular trophoblast and decidual
      endothelial cells: implications for vascular invasion during implantation.
AB  - During the process of implantation, maternal spiral arteries within the decidua
      are invaded by trophoblast cells that adhere to and migrate along the luminal
      surface of the vascular endothelial cells. This phenomenon resembles the events
      that occur during the migration of neutrophils into an acute inflammatory site,
      therefore it is possible that similar mechanisms are involved. Indeed, previous
      observations have shown that endovascular trophoblast expresses the blood group
      related antigen sialyl Le(x). In this study, we show, by immunohistology, the
      expression of both E- and P-selectin by vascular endothelial cells only in the
      decidua basalis and not in decidua parietalis. In contrast, ICAM-1 is expressed
      by all vascular endothelium throughout the decidua. Expression of VCAM-1 is
      variable at the implantation site, and is not expressed by vascular endothelial
      cells in decidua parietalis. Interestingly, we demonstrate the strong expression
      of a polysialylated form of NCAM by endovascular trophoblast. Our data suggests
      that vascular invasion by trophoblast is regulated by the expression of
      appropriate adhesion molecules which permit interaction between endovascular
      trophoblast and decidual endothelial cells.

PMID- 7516078
TI  - In vivo dopamine-D2 and serotonin-5-HT2 receptor binding study of risperidone and
      haloperidol.
AB  - An in vivo receptor binding technique was applied to evaluate the affinities of
      risperidone and haloperidol for dopamine-D2 receptors (D2) and serotonin-5-HT2
      receptors (5-HT2) in rat brain with [3H]YM-09151-2 and [3H]ketanserin as
      selective ligands. Radioactivities were obtained in the striatum frontal cortex,
      and cerebellum of the rats treated with the ligands. Time course study of
      receptor occupancy at 25 to 250 min after single doses of the drugs (1 mg/kg, IP)
      showed higher 5-HT2 occupancy in the frontal cortex and lower D2 occupancy in the
      striatum by risperidone than by haloperidol. Dose-response analysis of receptor
      occupancy revealed risperidone demonstrated higher binding affinity for 5-HT2
      than for D2, while the reverse was observed with haloperidol. It appeared that
      risperidone (1 mg/kg, IP), but not haloperidol (1 mg/kg, IP), demonstrated
      regional selectivity in D2 occupancy favouring frontal cortex more than the
      striatum. That risperidone displayed a higher ratio of 5-HT2 to D2 in occupancy
      than haloperidol is in agreement with the previous findings obtained in vitro.

PMID- 7516079
TI  - Nitric oxide synthase inhibition selectively potentiates swim stress
      antinociception in rats.
AB  - Since nitric oxide (NO) has been implicated in nociceptive processing, the
      present study examined whether NO synthase inhibition with either Nw-nitro-L
      arginine (L-NA) or its methyl ester (L-NAME) would alter antinociception elicited
      by either continuous (CCWS) or intermittent cold-water swims (ICWS) on the tail
      flick and jump tests. Whereas CCWS antinociception on both tests was
      significantly potentiated by a dose range of L-NA (0.1-4 mg/kg IP) and L-NAME (1
      mg/kg IP), ICWS antinociception was largely unaffected by these manipulations. In
      contrast, administration of the less active D isomer (D-NAME) failed to alter
      CCWS antinociception and reduced ICWS antinociception. The ability of NO synthase
      inhibition to potentiate CCWS antinociception could not be explained by changes
      in CCWS hypothermia. Since ICWS antinociception is mediated by mu-opioid
      manipulations and CCWS antinociception is sensitive to delta-opioid and nonopioid
      manipulations, this indicates that NO synthase inhibition may be acting upon a
      selective form of pain inhibition.

PMID- 7516081
TI  - Temporal and spatial regulation of 1-aminocyclopropane-1-carboxylate oxidase in
      the pollination-induced senescence of orchid flowers.
AB  - Pollination of many flowers initiates a sequence of precisely regulated
      developmental events that include senescence of the perianth and development of
      the ovary. The plant hormone ethylene is known to play a key role in regulating
      the biochemical and anatomical changes that constitute the postpollination
      syndrome. For this reason, we have studied the pollination syndrome in
      Phalaenopsis orchids by examining the spatial and temporal location of ethylene
      biosynthesis within the orchid flower, and how this biosynthesis is regulated by
      factors that influence expression of genes that encode key enzymes in the
      ethylene biosynthetic pathway. In particular, we examined the role in the
      postpollination syndrome of the expression of the gene for 1-aminocyclopropane-1
      carboxylate (ACC) oxidase, which catalyzes the conversion of ACC to ethylene. In
      vivo incubation of tissues with the ethylene precursor ACC demonstrated that ACC
      oxidase activity increases after pollination in the stigma, contrary to the
      observation that activity is constitutive in petunia and carnation gynoecia. RNA
      blot hybridization of floral tissues indicates that the increase in ACC oxidase
      activity is due to de novo synthesis of mRNA and presumably protein, which is
      induced after pollination. Furthermore, the pattern of induction is consistent
      with a model of coordinate regulation of gene expression in which the pollination
      signal travels to other organs of the flower to induce their ethylene production.
      We have also used in situ hybridization to define further the temporal and
      spatial expression of ACC oxidase within the floral organs, showing that
      expression, and,by inference, the capability to oxidize ACC to ethylene, is
      induced in all living cells of the tissues examined after pollination. These
      findings contrast with work in petunia that suggests that ACC oxidase is
      localized to the stigmatic surface.

PMID- 7516083
TI  - Expression of the costimulatory molecule B7/BB1 in autoimmune thyroid disease.
AB  - Efficient antigen presentation requires the provision of a costimulatory signal,
      the best characterized of which is B7/BB1. It is unclear whether thyroid cells
      expressing class II molecules can present autoantigens to T cells, although this
      has been suggested as an important mechanism in the initiation of Graves' disease
      and Hashimoto's thyroiditis. We have found that thyroid cells from patients with
      thyroid autoimmunity do not express B7/BB1 in vivo or in vitro, even after
      activation with the cytokines interleukin-1 or gamma-interferon, or with a
      phorbol ester. Increased numbers of CD20+ B cells and CD14+ dendritic cells
      expressing B7/BB1 were found in intrathyroidal lymphocyte preparations from such
      patients compared to peripheral blood. These results suggest that conventional
      antigen-presenting cells rather than thyroid cells provide B7/BB1 costimulatory
      activity in autoimmune thyroid disease, and argue against a role for the thyroid
      cells themselves in autoantigen presentation to T cells via the B7/BB1 pathway.

PMID- 7516082
TI  - Differential expression within the glutamine synthetase gene family of the model
      legume Medicago truncatula.
AB  - The glutamine synthetase (GS) gene family of Medicago truncatula Gaertn. contains
      three genes related to cytosolic GS (MtGSa, MtGSb, and MtGSc), although one of
      these (MtGSc) appears not to be expressed. Sequence analysis suggests that the
      genes are more highly conserved interspecifically rather than intraspecifically:
      MtGSa and MtGSb are more similar to their homologs in Medicago sativa and Pisum
      sativum than to each other. Studies in which gene-specific probes are used show
      that both MtGSa and MtGSb are induced during symbiotic root nodule development,
      although not coordinately. MtGSa is the most highly expressed GS gene in nodules
      but is also expressed to lower extents in a variety of other organs. MtGSb shows
      higher levels of expression in roots and the photosynthetic cotyledons of
      seedlings than in nodules or other organs. In roots, both genes are expressed in
      the absence of an exogenous nitrogen source. However the addition of nitrate
      leads to a short-term, 2- to 3-fold increase in the abundance of both mRNAs, and
      the addition of ammonium leads to a 2-fold increase in MtGSb mRNA. The nitrogen
      supply, therefore, influences the expression of the two genes in roots, but it is
      clearly not the major effector of their expression. In the discussion section,
      the expression of the GS gene family of the model legume M. truncatula is
      compared to those of other leguminous plants.

PMID- 7516085
TI  - Effectiveness of concomitant setiptiline maleate (Tecipul) on negative symptoms
      of schizophrenia.
AB  - 1. Setiptiline maleate was administered to schizophrenic patients with the object
      of improving their negative symptoms. 2. Moderate improvements were observed in
      58% of the treated patients, thus usefulness of this drug was demonstrated. 3.
      There was no aggravation of symptoms, and side effects were minor. 4.
      Measurements of plasma monoamine metabolites showed a tendency of MHPG to
      decrease and a significant decrease in 5-HIAA, but no change in the level of HVA
      was observed, suggesting a relationship between the negative symptoms and
      noradrenaline and/or serotonin systems.

PMID- 7516084
TI  - Malignant biliary obstruction: preliminary results of palliative treatment with
      hepaticogastrostomy under fluoroscopic, endoscopic, and laparoscopic guidance.
AB  - PURPOSE: To report a technique of peripheral biliary decompression by means of
      anastomosis of a bile duct in segment II of the liver to the lesser curvature of
      the stomach. MATERIALS AND METHODS: Seven patients with unresectable biliary
      neoplasm were treated. After transhepatic catheterization of a segment II bile
      duct, the left lobe of the liver and the lesser curvature of the stomach were
      perforated under fluoroscopic and laparoscopic guidance. Anastomosis between the
      biliary tree and the stomach was maintained with a gastrostomy tube placed across
      the tract. After 2 weeks, the tube was removed and patency of the tract was
      preserved with a metallic stent. RESULTS: Three patients died, at 3, 6, and 9
      months, respectively, without reocclusion; the other four were alive at 5 months
      without jaundice. One patient had an episode of cholangitis, which was resolved
      with antibiotic therapy. CONCLUSION: This method yields a good patency rate with
      few problems. Further investigation is required to evaluate long-term patency and
      the necessity of laparoscopic guidance.

PMID- 7516080
TI  - Structure and expression of chloroplast-localized porphobilinogen deaminase from
      pea (Pisum sativum L.) isolated by redundant polymerase chain reaction.
AB  - Porphobilinogen (PBG) deaminase catalyzes the polymerization of four PBG
      monopyrrole units into the linear tetrapyrrole hydroxymethylbilane necessary for
      the formation of chlorophyll and heme in plant cells. Degenerate oligonucleotide
      primers were designed based on amino acid sequence data (generated by mass
      spectrometry) for purified PBG deaminase from pea (Pisum sativum L.)
      chloroplasts. These primers were used in TaqI polymerase-catalyzed polymerase
      chain reaction (PCR) amplification to produce partial cDNA and nuclear genomic
      fragments encoding the enzyme. Subsequently, a 1.6-kb cDNA was isolated by
      screening a cDNA library constructed in lambda gt11 from leaf poly(A)+ RNA with
      the PCR products. The cDNA encodes an approximately 40-kD polypeptide containing
      a 46-amino acid NH2-terminal transit peptide and a mature protein of 323 amino
      acids. The deduced amino acid sequence of the mature pea enzyme is similar to PBG
      deaminases from other species and contains the conserved arginine and cysteine
      residues previously implicated in catalysis. Northern blot analysis indicates
      that the pea gene encoding PBG deaminase is expressed to varying levels in
      chlorophyll-containing tissues and is subject to light induction.

PMID- 7516086
TI  - Radiotherapy in the management of epidemic Kaposi's sarcoma of the oral cavity,
      the eyelid and the genitals.
AB  - From January 1987 to December 1992, 420 patients with acquired immunodeficiency
      syndrome (AIDS)-related epidemic Kaposi's sarcoma (EKS) were treated with
      radiotherapy at the oncology department in the Henri Mondor Hospital. Of these,
      146 (34.7%) exhibited tumours at 186 sites; 35 were oral, 102 eyelid or
      conjunctival (ophthalmic), and 49 penile or scrotal (genital) sites. Most
      patients had received prior chemotherapy. Radiation therapy consisted of 4 MV or
      45 kV X-rays, depending on tumor size and location. Doses ranged from 10 to 30
      Gy, according to tumor response and toxicity. In oral lesions mucosal reactions
      were often observed after relatively low doses of radiotherapy. In 27 patients
      receiving 15 Gy, severe reactions were observed in 6 (22%), moderate reactions in
      4 (15%) and mild reactions in 17 (63%). By contrast, irradiation of eyelid or
      conjunctival lesions and genital lesions, was well-tolerated. Treatment was
      generally successful in achieving good symptom palliation. Eyelid and
      conjunctival Kaposi's sarcoma seemed to be more radiosensitive when compared with
      cutaneous sites: a high objective remission rate (96%, 98/102) was observed at
      doses ranging from 10 to 20 Gy. Penile and scrotal lesions showed a good response
      to low dose radiation (complete response was scored in 34/49 patients (69.4%)). A
      meticulous evaluation of tolerance was necessary. Toxicity of oropharyngeal
      irradiation at relatively low doses is an argument for a restrictive use of this
      procedure in oral lesions.

PMID- 7516087
TI  - Mitogenic action of TGF-beta and insulin in L-929 cell line in serum-free medium.
AB  - In serum-free medium, TGF-beta, in a wide range of concentrations, stimulated DNA
      synthesis. A similar effect was achieved with insulin even after relatively short
      times. When TGF-beta and insulin were present simultaneously, the mitogenic
      effect was stronger than the effect achieved by either one separately, but
      without synergism. The PDGF, which is not mitogenic by itself in this cell line,
      did not increase the response to TGF-beta. In the presence of fetal bovine serum
      TGF-beta and insulin DNA synthesis was not stimulated. Two of the most important
      mitogenic growth factors for L-cells present in serum could be insulin and TGF
      beta. Adenosine did not modify the mitogenic response to TGF-beta and insulin.
      However, in the presence of adenosine PDGF stimulated the growth of L-929. The
      results suggest that TGF-beta does not stimulate the growth of L-929 via an
      autocrine production of PDGF-related peptides in a serum-free model. TGF-beta
      blocked the inhibitory response to estradiol at high concentrations, but it did
      not affect the inhibitory response due to glucocorticoids. Insulin and TGF-beta
      caused an enhancement of beta-NGF and c-myc RNA expression. This effect appears
      much earlier with insulin. This difference suggests that mRNA accumulation
      provoked by TGF-beta is mediated by other factors. Fetal bovine serum had little
      effect on the expression of those two mRNAs.

PMID- 7516088
TI  - [Evaluation of 3 diagnostic methods in premature rupture of membranes: diamine
      oxidase assay, alpha-fetoprotein assay, colorimetric method evaluating the pH].
AB  - The authors set out to assess the three diagnostic methods available which can
      detect early breaking of the membranes: radio-enzymatic assay of diamine-oxidase
      (DAO), radioenzymatic assay of alpha-fetoprotein (AFP), colorimetric method for
      determining pH (Amnicator). Between June 1991 and March 1992, 114 samples of
      vaginal secretions were taken from 104 pregnant patients being followed up at
      Maternity Unit A, Bordeaux (France). The results of the assays were expressed in
      quantitative terms (microU/ml for DAO and ng/ml for AFP); ROC (Receiver Operating
      Characteristic) curves were used to determine the positivity threshold in terms
      of the sensitivity and specificity (20 microU/ml for DAO and 15 ng/ml for AFP).
      The sensitivity of the pH test was 97.5%, which was significantly better than
      that of DAO (90.2%) and even that of AFP (82.9%). However, there was no
      difference between the specificities of the pH, DAO and AFP tests (93.3%, 96.6%
      and 93.5% respectively). The data were compared with those in the literature. The
      problems in collecting the vaginal secretions probably accounts for the better
      results of the colorimetric test. This is a reliable, fast and easily
      reproducible test; these qualities make it the preferred test in EBM, and it can
      be completed using a radioenzymatic method (DAO) or immunoradiometric test (AFP).

PMID- 7516089
TI  - [First reported case of preoperative ultrasonic diagnosis and laparoscopic
      treatment of unilateral, twin tubal pregnancy].
AB  - Since the first case of a unilateral tubal twin pregnancy was reported by Deott
      in 1891, on average, one case is reported per year in the literature. Ninety-nine
      such cases have been described and the present case is described as the one
      hundredth. The unilateral twin pregnancies were diagnosed during or after surgery
      in all but two cases. Santos et al. described the first unilateral, tubal twin
      pregnancy to be diagnosed before surgery through the use of ultrasound. Sherer et
      al. describe the second such case detected by ultrasound from the beating of the
      fetal heart by the abdominal ultrasound probe. We describe here the first case of
      unilateral, tubal twin pregnancy to be documented by ultrasound, with cardiac
      activity of two foetuses detected by the endovaginal probe. Furthermore, this
      case was treated by laparotomy, which had not previously been described.

PMID- 7516090
TI  - Impaired lipopolysaccharide-induced interleukin-1-beta production in patients
      with anti-hepatitis C virus antibody-positive chronic liver disease.
AB  - The aim of our study was to determine the role of cytokine interleukin-1-beta (IL
      1-beta) in patients with chronic hepatitis C virus (HCV) infection. Twenty-eight
      patients with chronic HCV infection were studied and compared with 18 healthy
      subjects. IL-1-beta levels were measured with an enzyme-linked immunosorbent
      assay in plasma and in supernatants of peripheral blood mononuclear cells (PBMC)
      incubated alone or in the presence of lipopolysaccharide (LPS). No IL-1-beta was
      found in plasma or unstimulated PBMC supernatants. The mean LPS-induced IL-1-beta
      production was 20.0 +/- 4.0 ng/ml in patients with chronic HCV infection and 29.4
      +/- 3.7 ng/ml in the control group. The patients had significantly lower levels
      of LPS-induced IL-1-beta than the control group (p < 0.00001). No difference in
      LPS-induced IL-1-beta production was found in patients in relation to the
      histologic diagnosis (p > 0.05). There was no correlation between LPS-induced IL
      1-beta production and serum alanine aminotransferase levels in patients with
      chronic HCV infection (r = 0.37, p > 0.05). Although limited to a small number of
      cases, our results suggest that LPS-induced IL-1-beta production by PBMC is
      impaired in patients with chronic HCV infection.

PMID- 7516092
TI  - Risks in using transgenic plants?

PMID- 7516093
TI  - Standard chemotherapy in squamous cell head and neck cancer: what we have learned
      from randomized trials.

PMID- 7516091
TI  - [Which way ahead? Carcinoma of the exocrine pancreas, the gallbladder and the
      bile ducts--nonsurgical therapy in the locally advanced and in the metastasized
      stage].
AB  - Carcinomas of the pancreas, gallbladder and bile ducts in inoperable stages can
      be treated with chemotherapy, radiotherapy and a combination of both modalities.
      Therapy is always palliative. In the past 20 years treatment results have not
      improved. Patients treated should be entered in controlled clinical studies with
      new substances randomized versus less toxic 5-FU or optimum supportive care. Pain
      and jaundice can be relieved by radiotherapy, bypass surgery and stent insertion.
      The choice of an option should be made according to patient characteristics and
      risk factors, as well as the possibilities and experience of the treating center.

PMID- 7516094
TI  - Induction chemotherapy with and without recombinant human granulocyte colony
      stimulating factor support in locally advanced stage IIIA/B non-small cell lung
      cancer.
AB  - Patients with non-small cell lung cancer (NSCLC) in stage IIIA with more than
      minimal N2 involvement or in stage IIIB are considered unresectable. Response
      rates to chemotherapy for these patients are in the range of 40%. Reduction of
      tumor mass by induction chemotherapy may lead to resectability and to improved
      survival. We evaluated response rates and determined influence of induction
      chemotherapy on survival when followed by surgery and radiotherapy in 60 patients
      with primarily inoperable stage IIIA/IIIB NSCLC. The following cytotoxic regimens
      were used: cisplatin (100 mg/m2) and vindesine (3 mg/m2); ifosfamide (10 g/m2)
      and etoposide (360 mg/m2); or a combination of cisplatin (75 mg/m2), ifosfamide
      (6 g/m2), and etoposide (360 mg/m2). Sixty patients were treated with two to four
      cycles of these regimens between June 1988 and October 1992. In 40 patients
      chemotherapy was repeated every 4 weeks. In 20 patients chemotherapy was
      intensified by interval reduction to 3 weeks with recombinant human granulocyte
      colony-stimulating factor (r-metHuG-CSF, filgrastim) support. The median patient
      age was 54 years, and Eastern Cooperative Oncology Group performance status was 0
      to 2. Distribution of stages IIIA and IIIB was 21 and 39 in all patients and 5
      and 15 in the group treated with r-metHuG-CSF support, respectively. The overall
      response rate (complete plus partial responses) was 35%. In patients treated with
      intensified chemotherapy and r-metHuG-CSF support, the response rate was 60%. In
      37 patients (61.6%) tumor was resected 4 to 6 weeks after the last cycle of
      chemotherapy; R0 resection was achieved in 22 patients, R1 in eight patients, and
      R2 in seven patients. With a follow-up of 4 to 60 months, 1-year survival in
      patients with tumor regression after chemotherapy and tumor resection was 82.2%
      versus 35.7% in nonresponders; 2-year survival of responders and nonresponders
      was 50.9% and 12.8%, respectively; and median survival was 23 months and 9
      months, respectively (P < .001). Median survival rates for responders with stage
      IIIA and IIIB disease were 39 and 17 months, respectively. Median survival after
      response to chemotherapy and incomplete resection (11 patients) was 17 months,
      whereas median survival after response to chemotherapy and complete resection (18
      patients) has not yet been reached. Only four patients in this group have died
      with a follow-up of 4 to 60 months. Of 20 patients receiving accelerated
      chemotherapy with r-metHuG-CSF support, World Health Organization grades 3 and 4
      neutropenia occurred in five and eight patients, respectively.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7516095
TI  - [The global tuberculosis problem. An apparition from history?].
AB  - Tuberculosis is increasing, partly because of concomitant HIV-infection, but with
      poverty and lack of social welfare and public health services contributing
      substantially. Current treatment for tuberculosis has proved efficacious also in
      HIV-infected patients, and so far seems to have prevented increased transmission
      of the disease in Tanzania. Strictly controlled chemotherapy provides the only
      hope of preventing the emergence of multi-resistant tubercle bacilli. The World
      Bank has evaluated tuberculosis control as the most cost-effective form of health
      intervention among adults. Norway has made a substantial contribution to the
      development of a model for tuberculosis control in developing countries and to
      international mycobacterial research; and therefore has a special responsibility
      to meet the new challenge.

PMID- 7516096
TI  - Comparative hyaline droplet nephropathy in male F344/NCr rats induced by sodium
      barbital and diethylacetylurea, a breakdown product of sodium barbital.
AB  - Hyaline droplet nephropathy in male rats due to alpha 2u-globulin accumulation in
      proximal tubules is caused by chemicals from several chemical classes. We have
      previously shown that the well-known sedative/hypnotic barbiturate, sodium
      barbital, and its breakdown product, diethylacetylurea, are renal toxins and
      renal tumor promoters. To determine comparative induction of hyaline droplets in
      renal tubules by sodium barbital and diethylacetylurea, male F344/NCr rats, 6
      weeks of age, were given diets containing 0, 170, 341, 500, or 1000 ppm of
      diethylacetylurea or containing 500, 1000, or 4000 ppm of sodium barbital for
      periods of 2 or 10 weeks. Rats were terminated at 2 or 10 weeks and the histology
      of the kidney was evaluated using light microscopy with hematoxylin and eosin
      staining and staining by the Heidenhain method. Quantitative analysis showed dose
      responses for the degree of droplet accumulation in the P2 and P3 segments of the
      proximal tubules. Diethylacetylurea was more potent. Immunohistochemistry and
      ultrastructural evaluation revealed the nature of the droplets. Western blotting
      confirmed the presence of alpha 2u-globulin. Renal tubular necrosis,
      regeneration, and increased levels of cell proliferation using proliferating cell
      nuclear antigen immunohistochemistry were also found. Female rats similarly
      exposed to each chemical did not show tubule droplet accumulations nor renal
      lesions. We confirm for the first time that these two chemicals can be added to
      the enlarging list of nephrotoxic chemicals inducing alpha 2u-globulin
      nephropathy and possessing tumor promoting and renal carcinogenic properties.

PMID- 7516097
TI  - Dexamethasone, beta-estradiol, and 2,3,7,8-tetrachlorodibenzo-p-dioxin elicit
      thymic atrophy through different cellular targets.
AB  - The effects of single doses of dexamethasone (DEX), beta-estradiol-17-valerate
      (E2), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the kinetics of thymic
      atrophy and related bone marrow and thymocyte phenotype alterations were
      examined. The results imply differences in the mechanisms by which these
      compounds act. Of the three compounds, DEX induced maximal atrophy by 3 days with
      complete recovery by Day 12. At the point of maximal atrophy, the RAG
      1+TdT+CD4+8+3int thymocyte population was proportionately the most depleted. In
      contrast, TCDD and E2 caused maximal thymic atrophy by Day 12. E2 treatment, like
      DEX, resulted in a preferential decrease in the RAG-1+TdT+CD4+8+3int population,
      but unlike DEX, this decrease persisted. TCDD-induced thymic atrophy resulted
      from a proportional loss of all classes of thymocytes. There was no significant
      relative reduction of TdT+RAG-1+ cells by TCDD in the thymus. A slow and
      persistent reduction of TdT and RAG-1 in bone marrow by both TCDD and E2
      contrasted with the rapid reduction and quick recovery of these markers in marrow
      from DEX-treated animals. Additional studies showed that only DEX-induced atrophy
      was accompanied by the induction of thymocyte apoptosis, as detected by multiple
      nucleosomal length DNA fragments within the first 24 hr. The different kinetics
      and proportions of subsets in the atrophied thymuses, as well as the distinct
      patterns of alterations of RAG and TdT expression, and the presence or the
      absence of apoptosis provide evidence for different mechanisms of thymic atrophy
      by these agents. The slow induction and longer persistence of thymic atrophy
      induced by E2 and TCDD, as well as their effects on bone marrow stem cell
      markers, suggest that bone marrow thymocyte precursors are major targets for
      these agents.

PMID- 7516098
TI  - Effects of selected anti-tumor-promoting chemicals on metabolic cooperation
      between Chinese hamster V79 cells.
AB  - Many tumor-promoting chemicals inhibit gap junctional communication between
      cells. We investigated the possibility that antipromoting chemicals may act
      inversely and enhance gap junctional communication. The V79/metabolic cooperation
      assay is an in vitro test that measures gap junctional communication indirectly
      by determining the extent of metabolic cooperation between mutant and wild-type
      V79 Chinese hamster lung fibroblasts in culture. Six in vivo antipromoters
      (caffeine, 3-isobutyl-1-methylxanthine (IBMX), phenidone, dibromoacetophenone,
      tosylphenylalanine chloromethyl ketone (TPCK), and acetic acid) were tested in
      this assay to assess their effects on metabolic cooperation. Caffeine, IBMX,
      phenidone, and dibromoacetophenone had no effect on metabolic cooperation, while
      TPCK slightly inhibited metabolic cooperation in one V79 assay. Acetic acid
      appeared to facilitate metabolic cooperation. In tests where an antipromoter was
      combined with the established tumor promoter phorbol 12-myristate 13-acetate
      (PMA), acetic acid, caffeine, and IBMX counteracted PMA-induced inhibition of
      metabolic cooperation, while phenidone, dibromoacetophenone, and TPCK had little
      effect. These results indicate that some antipromoters interfere with the ability
      of a tumor-promoting chemical to inhibit metabolic cooperation and suggest that
      alteration of gap junctional communication can be a mechanism of antipromoter
      action.

PMID- 7516099
TI  - NADPH-diaphorase positive cells in the chick and rat thymus.
AB  - Nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d) positive cells
      were demonstrated in the medulla of the rat and chick thymus at light microscopic
      level. The NADPH-d positive cells were present as clusters and were predominantly
      localized near the corticomedullary boundary. These clusters were closely
      associated with the thymic cysts. Some cells were seen in close proximity to
      blood vessels. The presence of nitric oxide (NO) as indicated by the positive
      NADPH-d reaction in the cells forming the wall of the thymic cyst suggests a
      modulatory influence of NO over the activities of these cells. Other possible
      functions of NO are also discussed.

PMID- 7516100
TI  - [Treatment of cancer pain with continuous opioid via spinal catheters].
AB  - Continuous intrathecal morphine treatment of cancer pain is reviewed on the basis
      of a literature search. Clinical, pharmacological and technical aspects are
      described, and the indications and potential complications are discussed. Three
      case histories illustrate the practical conduct and problems. The authors
      conclude that continuous intrathecal morphine treatment offers significant
      therapeutical advantages, when pain relief is not provided by conventional
      methods.

PMID- 7516101
TI  - [Continuous subcutaneous morphine to patients with terminal cancer. Analgesia at
      home].
AB  - Since 1992 it has been possible for cancer patients in the county of Southern
      Jutland to receive terminal care in their own homes. An essential part of this
      management is effective pain relief; more than 60% of cancer patients have
      chronic pain. In cases where oral medication or epidural administration of
      morphine is insufficient or complicated by side-effects continuous subcutaneous
      morphine administration may be suitable. The patient may be treated in this
      latter manner for long periods of time. A case story is described where a cancer
      patient was treated with continuous subcutaneous morphine in his home for more
      than 257 days without complications or major side-effects.

PMID- 7516102
TI  - An investigation of the suitability of three support matrices for the culture of
      cells derived from the secretory alveoli of the bovine mammary gland.
AB  - The suitability of three support matrices, (thick collagen gels, aluminium oxide
      and cellulose ester membranes, the latter two both thinly coated with collagen)
      for the production of primary cultures of bovine mammary epithelial cells was
      investigated. Single secretory alveoli were isolated from mammary tissue of
      animals in early lactation by enzymatic digestion and differential filtration.
      Cell growth was monitored by light and scanning electron microscopy. The
      cellulose ester membrane was found to give the best results, allowing growth of
      monolayers with a morphology closely resembling that of the natural epithelium of
      the gland. There were low levels of fibroblast contamination, and the membranes
      could be easily manipulated for further studies.

PMID- 7516103
TI  - [The specific antigens in the biological substrates of patients with
      salmonellosis in connection with enterosorption therapy].
AB  - There have been under observation 172 patients with gastrointestinal
      salmonellosis who besides conventional treatment were given 45 g of enterosgel or
      activated carbon daily in a single dose and divided into three taking in 15 g
      each. It was shown that enterosorbents did not delay formation of immune
      complexes in serum, neither interfered they with fixation of specific antigens by
      immune complexes at blood cells of patients with salmonellosis. Co-administration
      of enterosorbents promotes elimination of Salmonella's antigens which can be
      detected in coprofiltrate. Activated carbon in a single dose had the most
      pronounced eliminative effect.

PMID- 7516105
TI  - [Results following percutaneous intramedullary pin fixation in distal radius
      fractures].
AB  - 42 distal radius fractures have been submitted to further examination after
      percutaneous intramedullary pin fixation. The outcome were 95.3% of very good to
      good anatomic results and 90.5% of satisfying functional results. This showed the
      close link between the radiological-anatomical and functional results. The
      success of the treatment was very acceptable, although the Morbus Sudeck as the
      major complication--with 7.2%--was still relatively frequently observed. It could
      be seen that particularly fractures at the risk of dislocation with smash zone
      constituted an indication for the percutaneous intramedullary pin fixation, that
      is to say all fractures for which a retention is primarily difficult. It
      constitutes a supplement, as well as an extension to the therapy of the distal
      radius fractures.

PMID- 7516107
TI  - Persistence of viral RNA in the central nervous system of mice inoculated with
      MHV-4.
AB  - In order to study the role that viral persistence may play in chronic central
      nervous system (CNS) disease induced by murine coronaviruses, we have used the
      reverse transcriptase-polymerase chain reaction (RT-PCR) to study viral RNA in
      the brains of mice after intracerebral inoculation of JHM virus (JHMV or MHV-4).
      Quantitative RT-PCR showed that JHMV RNA decreased from approximately 2 ng/ug
      total brain RNA at day 6 post-inoculation (PI) to 0.1 pg/ug total brain RNA at
      360 days PI. Double-stranded viral RNA could be detected up to day 20 PI. By the
      selective use of upstream or downstream primers during the RT step, it was
      possible to measure negative sense and positive sense JHMV RNA respectively, and
      we found that there was a marked rise in the ratio of positive to negative sense
      JHMV RNA after day 13 PI. Analysis of amplified products by dideoxy DNA
      sequencing showed that the characteristic mutation of our input virus (at
      position 3340 of gene 3) is maintained to at least day 42 PI. Taken together,
      these results favor a model of JHMV persistence in vivo in which viral RNA is
      present as double stranded forms initially and predominantly as single stranded,
      positive sense forms at late timepoints. Further analysis of this model in
      quantitative terms may contribute to our understanding of the biological
      significance of coronavirus persistence in the CNS.

PMID- 7516104
TI  - The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical
      role for tumor-derived vascular permeability factor.
AB  - Cerebral edema and fluid-filled cysts are common accompaniments of brain tumors.
      They contribute to the mass effect imposed by the primary tumor and are often
      responsible for a patient's signs and symptoms. Cerebral edema significantly
      increases the morbidity associated with tumor biopsy, excision, radiation
      therapy, and chemotherapy. Both edema and cyst formation are thought to result
      from a deficiency in the blood-brain barrier, with consequent extravasation of
      water, electrolytes, and plasma proteins from altered tumor microvessels. The
      resultant expansion of the cerebral interstitial space contributes to the
      elevated intracranial pressure observed with brain tumors. Departure from the
      typical blood-brain barrier microvascular architecture may only partially explain
      the occurrence of edema and tumor cyst formation. Biochemical mediators have also
      been implicated in vascular extravasation. Vascular permeability factor or
      vascular endothelial growth factor (VPF/VEGF) is a protein that has recently been
      isolated from a variety of tumors including human brain tumors. VPFb is an
      extraordinarily potent inducer of both microvascular extravasation (edemagenesis)
      and the formation of new blood vessels (angiogenesis). Its role in tumor growth
      and progression would therefore appear pivotal. Herein, the author presents an
      updated account of the investigation of VPF. Historical and clinical perspectives
      of the study and treatment of tumor associated edema are provided. The efficacy
      of high-dose dexamethasone in the treatment of neoplastic brain edema is
      discussed. A hypothetical role for VPF in edemagenesis is presented and
      discussed. It is hoped that an expanded understanding of the mechanisms
      responsible for the genesis of edema will ultimately facilitate therapeutic
      intervention.

PMID- 7516108
TI  - Enhancement of FIP in cats immunised with vaccinia virus recombinants expressing
      CCV and TGEV spike glycoproteins.

PMID- 7516109
TI  - Determination of the cytotoxic T cell epitopes of mouse hepatitis virus, using
      elution of viral peptides from class I MHC molecules as an approach.

PMID- 7516110
TI  - Induction of an immune response to transmissible gastroenteritis coronavirus
      using vectors with enteric tropism.

PMID- 7516111
TI  - Establishment of MHV-A59 S protein specific cytotoxic T lymphocyte clones.

PMID- 7516106
TI  - Mouse hepatitis virus and herpes simplex virus move along different CNS pathways.
AB  - The spread of mouse hepatitis virus, strain JHM and herpes simplex virus type 1
      in the central nervous system after inoculation into the nares and main olfactory
      bulb has been examined. The results show that each virus infects a subset of the
      possible connections of the olfactory bulb and that the subset infected by each
      virus is different. Thus, both viruses will be useful for studying the
      neuroanatomic connections of the olfactory bulb, and possibly for functional
      analyses as well.

PMID- 7516112
TI  - Functional relationship between cyclic AMP-dependent protein phosphorylation and
      platelet inhibition.

PMID- 7516113
TI  - The biological and pharmacological role of nitric oxide in platelet function.

PMID- 7516116
TI  - Determination of handwash removal efficiency: incomplete removal of the pesticide
      chlorpyrifos from skin by standard handwash techniques.
AB  - This study was designed to develop standard procedures whereby the removal
      efficiency of handwash techniques can be determined. A known amount of the
      insecticide chlorpyrifos (Dursban), was transferred to the hands of volunteers,
      which were washed by a standard technique. The following experimental variables
      were studied: time between exposure and washing, washing solvent, and skin
      loading. Ethanol removed only 30% of the chlorpyrifos on skin at loadings of
      approximately 7 micrograms/cm2, with residence time on skin having no effect.
      Prewashing with ethanol increased removal efficiency. A 10% isopropanol/distilled
      water wash removed 43% immediately following exposure, and 23% one hour post
      exposure, with skin loadings of approximately 12 micrograms/cm2. Removal
      efficiency immediately following contact decreased for lower skin loading levels
      (21-23% for loadings of 0.1-1 micrograms/cm2). These findings indicate that
      substantial amounts of the insecticide were either absorbed through or adsorbed
      to the skin, and that pesticide residue levels recovered by standard handwashing
      techniques are unlikely to represent accurate estimates of dermal exposure.
      Approximately two-fold to five-fold underestimations of exposure can occur for
      pesticides with handwash procedures similar to those tested. All experimental
      variables studied can each alter significantly the fraction of total pesticide on
      skin that handwashing removes. If handwashing is to be used to estimate dermal
      exposure in the workplace, appropriate laboratory-based removal efficiency
      studies should be conducted prior to field investigations. Further efforts should
      be made to develop accurate and reproducible hand measurement techniques.

PMID- 7516115
TI  - Misconceptions about morphine use in cancer patients.

PMID- 7516114
TI  - Rap1b and platelet function.

PMID- 7516117
TI  - The diagnostic value of silver nucleolar organizer region assessment in breast
      cytology.
AB  - Benign and malignant breast lesions in cytologic preparations can be difficult to
      distinguish. The authors applied the silver nucleolar organizer region (AgNOR)
      technique to cytologic preparations obtained from surgical specimens to evaluate
      its diagnostic usefulness in making this distinction. Sixty-two benign and 36
      malignant lesions were examined. AgNORs were counted and evaluated using a
      subjective scoring technique to examine AgNOR size, shape, and clustering. The
      benign lesions had a mean count of 4.44 AgNORs/nucleus (95% CI, 2.4-6.5) and the
      malignant cases, 9.52 AgNORs/nucleus (95% confidence interval, 7.4-11.7; P <
      .0005). The median score for benign cases was 7 and for malignant cases, 13 (P <
      .0001). With a few exceptions, cases with high counts had high scores. The
      diagnostic accuracy of combined counting and pattern assessment was 90%. The
      likelihood ratio for correct diagnosis using AgNOR counting was 14:1 and for
      AgNOR scoring, 13:1.

PMID- 7516118
TI  - DNA of Mycobacterium tuberculosis in formalin-fixed, paraffin-embedded tissue in
      tuberculosis and sarcoidosis detected by polymerase chain reaction.
AB  - Infection with Mycobacterium tuberculosis is a major cause of death worldwide.
      Identification of mycobacteria in tissue sections is usually easily achieved by
      acid-fast stains, but this method sometimes gives unsatisfactory results. The
      authors therefore compared conventional staining techniques and polymerase chain
      reaction (PCR) for mycobacterial DNA sequences in 24 selected tissue samples from
      patients with tuberculosis. In all samples, either positive or negative with acid
      fast stain, mycobacterial DNA fragments were detected. In addition, tissue
      samples from patients with clinically proven sarcoidosis were included as
      controls. Surprisingly, strong signals for mycobacterial DNA were found in 2 of
      15 cases. Polymerase chain reaction is a useful technique in the demonstration of
      mycobacterial DNA fragments in patients with clinically suspected tuberculosis
      who have acid fast stain-negative histology. An epithelioid granulomatous
      reaction in the lung, negative by acid-fast stain and positive for mycobacterial
      DNA by PCR, however, does not permit a diagnosis of tuberculosis, because a
      positive result can also be obtained in cases of sarcoidosis. In some cases of
      sarcoidosis, the causal agent might be either cell wall defective mycobacteria or
      persistent intracellular DNA from mycobacteria.

PMID- 7516120
TI  - Elevated MSAFP levels and congenital heart defects: lack of an association.
AB  - This study was undertaken to evaluate the relationship between elevated maternal
      serum alpha fetoprotein (MSAFP) levels and congenital heart defects. Thirty-two
      infants with isolated major congenital heart defects and whose mothers had had
      MSAFP screening were identified. In only one case was the MSAFP greater than 2.3
      multiples of the median. A review of our experience with women with elevated
      MSAFP levels did not document a higher rate of congenital heart malformations
      than would be expected based on estimated frequencies in the general population.

PMID- 7516119
TI  - Deletion (11)(q14.1q21).
AB  - We report on a 4-year-old girl with moderate developmental delay, horseshoe
      kidney, bilateral duplication of the ureters with right upper pole obstruction,
      hydronephrosis and nonfunction, and subsequent Wilms tumor of the right lower
      pole. She had an interstitial deletion of the long arm of chromosome 11 involving
      the region 11(q14.1q21).

PMID- 7516121
TI  - Mosaic tetrasomy 8p in two patients: clinical data and review of the literature.
AB  - We report on 2 girls with mosaic tetrasomy 8p. Patient 1 showed the extra iso 8p
      chromosome in 20% of cultured lymphocytes and 18% of cultured fibroblasts
      [46,XX/47,XX,+i(8p)]. She presented with growth retardation, mild facial
      alterations, and motor developmental delay. Patient 2 presented with
      developmental delay, hypotonia, and slight facial alterations; she had the extra
      iso 8p chromosome in 94% of cultured peripheral lymphocytes. The patients are
      compared to the 6 previously reported cases. In our experience, the presently
      reported patients clinically resemble children with inv dup(8)(p21-p22) and
      patients with mosaic trisomy 8.

PMID- 7516123
TI  - MS/MS with high detection efficiency and mass resolving power for product ions in
      Fourier transform ion cyclotron resonance mass spectrometry.
AB  - We present a new FT-ICR method for MS/MS of trapped ions. Parent ions isolated in
      the source trap of a dual-trap FT-ICR/MS instrument are subjected to off
      resonance dipolar excitation to promote collision-induced dissociation (CID),
      while product ions are simultaneously axialized by broad-band azimuthal
      quadrupolar excitation in the presence of argon collision gas. In this way,
      radial diffusional loss of product ions is greatly reduced; moreover, the
      axialized product ions may then be efficiently transferred to the analyzer trap
      for high-resolution detection. Significant improvements in FT-ICR detection
      efficiency, mass resolving power (m/delta m > or = 20,000 at m/z < or = 1000),
      and mass accuracy (< or = 50 ppm for peptide fragments of m/z < or = 1000) are
      demonstrated for CID product ions of the cyclic peptide, gramicidin S.

PMID- 7516122
TI  - [New immunobiologic trends concerning etiopathogenicity of cholesteatoma].
AB  - After an epoch in which was pretended to explain the etiopathogenetic phenomena
      observed in Cholesteatoma through enzymatic studies, nowadays other
      investigations focus the topic in the possible presence of immunobiologic
      alterations at cellular level, so the research work is directed to the
      occurrence, distribution and activity of several growth factors and leukins. In
      this paper the AA. made a perusal of the new acquisitions and devote themselves
      to two important aspects of the cholesteatoma: the biologic behaviour of the
      squamous cell epithelia with an uncontrolled growth and to the immunobiologic
      mechanisms responsible for the bone resorption.

PMID- 7516124
TI  - Localization of nitric oxide synthase in enteric neurons of the porcine and human
      ileocaecal junction.
AB  - Recent studies, using pharmacological or indirect morphological techniques,
      suggest that the non-adrenergic non-cholinergic (NANC) control of the ileocaecal
      junction (ICJ) is largely regulated by nitric oxide (NO). In this study, NO
      synthase (NOS) has been localized immunocytochemically and enzyme
      histochemically, using NADPH-diaphorase (NADPH-d), in enteric neurons of the
      myenteric and submucous plexuses of the ICJ of man and pig. The myenteric plexus,
      as well as the outer submucous plexus of both the porcine and the human ICJ,
      harboured NOS-containing neurons, which varied widely in size and shape, but
      which all displayed a multidendritic, uniaxonal appearance. Compared to the
      myenteric plexus, significantly fewer NOS-containing neurons were encountered in
      the outer submucous plexus. Neurofilament immunohistochemistry following NADPH-d
      application made it possible to distinguish a variety of cells that stained for
      both markers. Some of the larger neurons were of the Dogiel type-I morphology,
      whereas others showed a type III or a type VI-like morphology. A large number of
      NOS-immunoreactive nerve fibers were detected in the enlarged circular muscle of
      the ICJ and in the adjacent ileum. No NOS staining was detected in the smooth
      muscle cells of the outer circular or longitudinal muscle layer. The latter
      finding, together with the abundance of NOS positive nerve fibers in the smooth
      muscle layer, suggest a neuronal origin for NO as an important inhibitory
      neurotransmitter in the ICJ.

PMID- 7516125
TI  - Nitric oxide and synaptic function.

PMID- 7516126
TI  - GABAA receptor channels.

PMID- 7516127
TI  - [The nose: representation and symbolism].
AB  - The nose is a primordial element in the facial recognition among the human
      species. This privileged place, confirmed by experimental psychology, finds a
      professional application in the creation of the photofit. The physiognomonist
      drift, that flourished during the last century, lacked a scientific basis and
      gradually gave way. On the other hand, it is interesting to observe the artist's
      representations of the nose: except for the realistis school the nose is
      upsetting. It is therefore either stereotyped or deleted. As for the
      caricaturist, he illustrates the nose shamelessly. This representation is
      certainly related to the symbolic force of the nasal appendage, not only a vector
      of diverse and variable odours but also a passage for the spirit and to the
      heart. The nose is therefore a significative element of relation, of contact and
      of expression.

PMID- 7516128
TI  - Some environmental risk factors for childhood asthma: a case-control study.
AB  - A case-control study of the home environment of 140 asthmatic children and 140
      controls (matched for age, sex and socio-economic status) was carried out in two
      semi-urban Nigerian teaching hospitals. The mean age of the children was 66
      months, and the mean monthly family income was US $50.00. The average number of
      people in a household was seven, with a mean sleeping density of 4.9 persons per
      sleeping area. There was a strong and significant association between asthma and
      a damp, mouldy bedroom (OR = 11.2, p < 0.001), household pets (OR = 116.8, p <
      0.001), cigarette smoke (OR = 2.1, p < 0.01), mosquito coil (OR = 3.7, p <
      0.001), and rodents/cockroaches (OR = 113.7, p < 0.001). There was a curious but
      unexplained protective effect of indoor biomass smoke (OR = 0.6, p < 0.001),
      indoor plants (OR = 0.5, p < 0.01), mould growth elsewhere in the home (OR = 0.5,
      p < 0.01), and cosmetic aerosols (OR = 0.6, p < 0.05). Control of the micro- as
      well as the macro-environment of the asthmatic child as an adjuvant to drug
      therapy is discussed.

PMID- 7516129
TI  - Serotherapy in the management of scorpion sting in children in Saudi Arabia.
AB  - A total of 780 children with scorpion stings were admitted to a referral hospital
      in Saudi Arabia over a 7-year period. A similar number was managed in the
      outpatient department. The mortality was 4.8% initially, but no death occurred in
      the last 2 years of the study period. The reduction in mortality is attributed to
      the use of antivenom and improvement in case management.

PMID- 7516130
TI  - Immunodiagnosis of childhood pulmonary and extrapulmonary tuberculosis using
      Mycobacterium tuberculosis ES antigen by penicillinase ELISA.
AB  - The diagnostic potential for detection of IgG to Mycobacterium tuberculosis
      excretory secretory (ES) antigen in childhood pulmonary and extrapulmonary
      tuberculosis was explored. IgG antibody to M. tuberculosis ES antigen was
      detected by indirect penicillinase ELISA. Twenty (80%) out of 25 pulmonary
      tuberculosis cases (clinically diagnosed and/or AFB-positive), five of nine
      tuberculous pleural effusion cases and only six of 69 cases in the control group
      were positive for IgG antibody to M. tuberculosis ES antigen. All CSF and sera
      were positive for IgG antibody in 12 cases of clinically diagnosed tuberculous
      meningitis (TBM). Out of 35 cases in the control group for TBM, all five cases of
      pyogenic meningitis but none of the 13 cases of viral encephalitis, five cases of
      enteric encephalopathy and 12 cases with no CNS infection were positive for anti
      tubercular IgG antibody in CSF samples. Only two of them, i.e. one case of
      pyogenic meningitis and the other with no CNS infection, were positive for
      antibody in sera. The study demonstrated the potential of this assay in the
      diagnosis of tuberculosis in children where bacteriological confirmation is very
      difficult.

PMID- 7516132
TI  - The limitations of verbal autopsy in a malaria-endemic region.
AB  - Verbal autopsies are being used widely to describe the causes of mortality and to
      assess the effect of interventions against specific diseases in developing
      countries where many deaths occur at home. A verbal autopsy has been in use in
      the Upper River Division of The Gambia since 1988. In this paper we present the
      results of a validation study of this technique. One hundred and forty-one verbal
      autopsies were reviewed on two occasions by the same three physicians. In 38
      (27%) of the cases, the first and subsequent diagnoses differed. In 94 children
      admitted to Basse Health Centre, the results of verbal autopsies were compared
      with the diagnoses made by a paediatrician--only 44 (47%) matched. The poor
      sensitivity and specificity of the verbal autopsy in this study may have been due
      to the confounding effect of malaria, which can be difficult to distinguish from
      other causes of death in this community.

PMID- 7516131
TI  - Detection of naphthols and aflatoxins in Nigerian cord blood.
AB  - Widespread use of napthol-containing compounds and frequent contamination of
      foods by aflatoxins occurs in Nigeria. Napthols cause haemolysis and aflatoxins
      are hepatotoxic. A study was carried out to determine the extent of fetal
      exposure to these compounds and their influence on birthweight. Cord blood
      samples were collected at delivery from 625 babies and their sera were analysed
      for aflatoxins and naphthols. Mothers' histories and babies' weights were
      recorded. Naphthols were detected in 6.9% and aflatoxins in 14.6% of serum
      samples. No correlation was found between the presence of either compound and
      birthweight. Reported exposure to naphthalene-containing compounds was not
      related to detection of serum naphthol. Results show considerable fetal exposure
      to these potentially toxic compounds in Ibadan, Nigeria.

PMID- 7516133
TI  - Infant care in rural Malawi. A prospective study of morbidity and growth in
      relation to environmental factors.
AB  - In connection with the introduction of piped surface water delivered by community
      taps in a rural area of Malawi, 46 infants were studied prospectively during a 10
      month period to monitor infant care and health. Compared with the reference
      population, newborn infants generally weighed less and were shorter.
      Breastfeeding was universal and appeared adequate for catch-up in weight during
      the 1st 3 months. Growth faltering occurred from the age of 3 months when the
      prevalence of infectious diseases gradually increased and suitable supplementary
      foods were lacking. Babies were given highly contaminated water from the 1st days
      of life, but, in spite of this, diarrhoea was infrequent during the 1st 5 months
      when respiratory tract infections and episodes of fever were the most common
      symptoms of disease. Diarrhoea became a problem from the age of 5-6 months. No
      differences in morbidity or growth patterns were observed between infants using
      piped and traditional water sources. Thus, the quality of drinking water seemed
      to have no substantial effect on the health of the studied infants during the 1st
      months of life.

PMID- 7516135
TI  - Validity of clinical signs for the identification of pneumonia in children.
AB  - In a prospective study to determine simplified clinical signs predictive of
      pneumonia in children between 2 months and 5 years of age, and to test the
      validity of the signs recommended by the World Health Organization, clinical
      findings were correlated with X-ray evidence of pneumonia in 854 children, 400
      with pneumonia and 454 with upper respiratory infections (no pneumonia). A
      respiratory rate of > or = 50/min in infants 2-6 months of age, > or = 40/min in
      children 7-35 months, and > or = 35/min in children > or = 36 months was the best
      discriminator of radiological evidence of pneumonia. Use of a respiratory rate of
      > or = 50/min instead of > or = 40/min resulted in a 14%, 19% and 32% loss of
      sensitivity with little gain in specificity in the age groups 7-11 months, 12-35
      months and > or = 36 months, respectively. The age-specific respiratory rate
      (recommended by WHO) and/or chest indrawing, history of rapid or difficult
      breathing and/or chest indrawing, and nasal flaring were also sensitive and
      specific indicators of pneumonia in almost all the age groups studied.

PMID- 7516137
TI  - Hirschsprung's disease in Zaria, Nigeria: comparison of 2 consecutive decades.
AB  - This is a retrospective study of 136 histologically confirmed cases of
      Hirschsprung's disease (HD) seen and treated in a single centre over 2
      consecutive decades spanning the years from 1972 to 1991. Forty-six cases were
      seen in the 1st 10 years and 90 in the 2nd. Certain factors were considered to be
      responsible for the observed improvement during the 2nd decade; these included
      improvements in the mode of bowel preparation, the use of more effective
      antimicrobial agents with a wider spectrum of activity for prevention and
      treatment of established infections, and improvements in the pre-operative
      nutritional status of the patients and in the staging of the operations.
      Morbidity was minimal. Mortality dropped from 28.3% in the 1st decade to 5.6% in
      the 2nd. Causes of mortality in the 1st decade were pneumonia (8), aspiration of
      gastric contents (2), undernutrition (2) and haemorrhage from a dislodged clamp
      several days following a Duhamel procedure (1). In the early part of the 2nd
      decade, three patients died from anastomotic dehiscence following the Swenson
      procedure and two from aspiration pneumonia.

PMID- 7516138
TI  - Diagnostic and management problems in childhood visceral leishmaniasis in south
      western Saudi Arabia.
AB  - The diagnosis and management of childhood visceral leishmaniasis were studied in
      51 parasitologically proven cases from Abha, Saudi Arabia. Bone marrow aspiration
      was positive in 40 of 47 cases (85%). Splenic aspiration, though rarely used
      because of perceived dangers, was not associated with complications and revealed
      the parasite in all 12 cases in which it was used. There was prompt response to
      sodium stibogluconate, with defervescence in 93% and decrease of
      hepatosplenomegaly in 67% of patients within 1 week of commencing chemotherapy. A
      dose of 20 mg/kg/day for at least 3 weeks was generally safe and effective in
      achieving cure and preventing relapse. Two children with persistent massive
      splenomegaly after the first course responded to prolonged chemotherapy.
      Bronchopneumonia and severe cytopenia were common complications. Disseminated
      intravascular coagulation and hepatitis were associated with a poor outcome. The
      four patients who died had a progressive course with multiple complications.
      Early detection and appropriate management of complications may help to reduce
      morbidity and mortality in childhood visceral leishmaniasis.

PMID- 7516136
TI  - Autosomal recessive osteopetrosis in Arab children.
AB  - Nineteen Arab children including six boys and 13 girls in ten sibships were
      diagnosed as having osteopetrosis over a 5-year period in various hospitals in
      Kuwait. Eighteen patients had an isolated autosomal recessive form and one had
      autosomal recessive osteopetrosis associated with renal tubular acidosis. The
      mean age of diagnosis was 24 months. Parental consanguinity was high amongst them
      (68%). Anaemia, hepatosplenomegaly, failure to thrive, recurrent infections and
      neurological manifestations were common. Associated congenital abnormalities were
      found in 26%. Deafness, hydrocephalus and dental caries were relatively less
      common. A high mortality (37%) owing to infection was noted. The medical
      management and recommendations for patient care are discussed briefly.

PMID- 7516139
TI  - The occurrence of ataxia-telangiectasia and common variable immunodeficiency in
      siblings: case report.
AB  - Common variable immunodeficiency and ataxia-telangiectasia with immunodeficiency
      are both well recognized syndromes which occur in children. The aetiological
      factors responsible for both these conditions have yet to be defined clearly. The
      clinical and laboratory features in two siblings, one with common variable
      immunodeficiency and the other with ataxia-telangiectasia, are presented. This is
      the first report of these two entities occurring in siblings.

PMID- 7516140
TI  - Major congenital malformations among paediatric admissions at University College
      Hospital, Ibadan, Nigeria.
AB  - The pattern of major congenital malformations seen at University College
      Hospital, Ibadan, Nigeria among admitted children over a period of 5 years is
      reported. Their ages at presentation ranged from a few hours to 13 years, and the
      majority (72.7%) presented in infancy. The male:female ratio was 1.6:1.
      Cardiovascular, central nervous and gastro-intestinal malformations accounted for
      71.6% of all malformations. The commonest individual system malformations were
      congenital heart lesions, spina bifida, anorectal malformation and omphalocoele,
      while the highest case fatality rates were recorded in cases of oesophageal
      atresia, hydrocephalus, biliary atresia and posterior urethral valve. Overall
      mortality was 19.4%. The importance of both longitudinal and cross-sectional
      studies of congenital malformations in developing countries, while infectious
      diseases and malnutrition are being controlled, is emphasized.

PMID- 7516134
TI  - Meconium aspiration syndrome and neonatal outcome in a developing country.
AB  - The outcome in 148 inborn meconium-stained neonates was studied prospectively
      over a 5-month period. Fifty-three infants (38.5%) developed meconium aspiration
      syndrome (MAS). There was a significantly higher rate of MAS (p < 0.001),
      mechanical ventilation (p < 0.016) and hospital stay (p < 0.016) in neonates with
      meconium in the trachea than in neonates with no meconium in the oropharynx. The
      incidence of MAS was significantly higher and the duration of hospital stay
      longer in outborn than in inborn infants (p < 0.022).

PMID- 7516143
TI  - Impurities in granulocyte colony-stimulating factor?

PMID- 7516141
TI  - Double surface phototherapy on a fluid bed.
AB  - Jaundice is a common neonatal problem with a higher incidence in premature
      infants. Phototherapy is an established treatment modality, effective and safer
      than exchange transfusion. Double surface phototherapy is more effective. The
      present methods have drawbacks, viz limited availability, high cost of equipment
      and difficulties in nursing infants during phototherapy. A modification to the
      technique which overcomes these difficulties made with equipment available in
      most neonatal units is described with three case reports of hyperbilirubinaemia
      successfully treated using this method.

PMID- 7516142
TI  - Prevalence of nosocomial rotavirus infection in hospitalized children in Benin
      City, Nigeria.
AB  - A total of 1496 stool samples from 445 children admitted into the paediatric
      wards of the University of Benin Teaching Hospital, Benin City between November
      1989 and April 1990 were examined for the presence of rotavirus antigen. The
      total prevalence of rotavirus infection in this study was 28.1% (125 in 445).
      Fifty-four (12.1%) of the 445 children had nosocomial rotavirus infection: 22
      (9.6%) of the 230 children (neonates, infants and young children) who had
      diarrhoea and 32 (14.9%) of the 215 children (neonates, infants and young
      children) who had no diarrhoea. The importance of maintaining strict hygiene in
      hospital wards cannot be overemphasized.

PMID- 7516144
TI  - [Bronchopulmonary dysplasia. Course over 3 years in 88 children born between 1984
      and 1988].
AB  - BACKGROUND: The survival and outcome of infants with bronchopulmonary dysplasia
      (BD) depend on the patient's maturity, the severity of the BD and nutritional
      problems. This study evaluates the specific role of chronic pulmonary failure in
      the growth and development of infants recovering from BD. POPULATION AND METHODS:
      88 infants admitted for BD from January 1984 to December 1988, having gestational
      age from 25 to 41 weeks 5 days (mean: 29) and birth weight from 680 to 3,400 g
      (mean: 1,195) were studied. All infants were given respiratory support for 6 to
      914 days (mean 84) and oxygen therapy for 28 to 1,232 days (mean: 119). 29
      infants were given corticosteroids for more than 1 month. The outcome of the 80
      infants with gestational ages of less than 33 weeks was compared to that of 272
      infants with the same gestational age but not suffering from BD on their 28th
      day. The infants in both groups were examined at 2 years of age and classified
      as: a) handicapped (neurologic deficit, IQ < 80, hearing loss, blindness,
      convulsions); b) doubtful (transitory neurology dysfunction); c) normal. RESULTS:
      Of the 88 infants still living at the age of 28 days, 19 died before the age of 2
      years: 16 of the 64 surviving infants who could be followed until the age of 2
      years were classified as handicapped, 13 were considered doubtful and 35 were
      normal. The more significant risk factors for neurodevelopmental impairment were:
      a) the presence of porencephaly and/or ventricular dilatation on brain
      ultrasonography; b) head circumference < -2 SD at the end of hospital stay; c)
      oxygen therapy and hospitalization > 5-6 months. The group of infants with BD had
      a higher death rate (24% vs. 3.7 in the group without BD) and more frequent
      neurodevelopmental impairment at gestational ages of > 31-32 weeks. CONCLUSIONS:
      BD is an extra risk for the survival and neurodevelopment of infants with
      gestational age > 31 weeks.

PMID- 7516145
TI  - [The MASA syndrome (Mental retardation, Aphasia, Spastic paraplegia and Adducted
      thumbs), is it heterogeneous?].
AB  - BACKGROUND: MASA syndrome is the acronym for Mental retardation, Aphasia,
      Shuffling gait and Adducted thumbs. Linkage studies have shown linkage to markers
      in the Xq28 band. CASE REPORTS: Case no. 1: Mickael was examined at the age of 3
      yr 4 mo. He was mentally retarded (IQ = 40), aphasic, and had spastic gait,
      moderate facial dysmorphy and adducted thumbs. His parents were normal, except
      that his mother had similar facial dysmorphy. His brain CT scan was normal. Case
      no. 2: Philippe was the elder brother of Mickael. When examined at the age of 5
      years, he had the same features as his brother. His IQ was 40. His brain-CT scan
      was also normal. DNA analysis with markers for the Xq28 area showed that the
      brothers had received different X chromosomes from their mother. CONCLUSION: DNA
      studies suggest that the MASA syndrome is heterogeneous.

PMID- 7516147
TI  - Subunit interaction in B19 parvovirus empty capsids.
AB  - B19 parvovirus is a small single-stranded DNA virus with a genome that encodes
      only two structural proteins, designated VP1 and VP2. 60 copies of the structural
      proteins assemble into the viral capsid, with approximately 95% VP2 and 5% VP1.
      Recombinant empty capsids composed of VP2 alone or of VP2 and VP1 self-assemble
      into particles that are morphologically indistinguishable from full virions.
      Empty capsids containing both VP2 and VP1 elicit a strong neutralizing antibody
      response when used to immunize rabbits. Capsids containing only VP2 are similarly
      antigenic but elicit only weak neutralizing activity. We performed fine structure
      epitope mapping by measuring the reactivity of antisera raised against capsids
      composed of VP2 and VP1 or VP2 alone against 85 overlapping peptides spanning the
      sequence of the two structural proteins. A profile of the antigenic difference
      between empty capsids with and without VP1 was produced from the resulting data.
      This profile divided the sequence of the structural proteins into four regions
      that correlated well with expected viral structures. Thus, the addition of a
      small number of VP1 residues altered the antigenicity of the entire capsid. The
      major area of enhanced antigenicity is homologous to the spike of canine
      parvovirus, an area known to contain both neutralizing and host-range
      determinants. Our data are consistent with a model in which the unique region of
      VP1 is necessary for the virus to assume its mature capsid conformation.

PMID- 7516146
TI  - Restriction enzyme analysis of American region dengue viruses.
AB  - Restriction fragment heterogeneity of Hae III digestion products of cDNA to
      virion RNA was used to map the distribution of dengue virus topotypes found in
      the American region. By comparing the electrophoretic patterns of fragments
      produced, dengue virus isolates were placed in groups that agreed with those
      previously determined by oligonucleotide fingerprinting. Dengue-1 and dengue-4
      viruses occur throughout the western hemisphere as single genetic types, with
      most of the isolates sharing at least 70% of their Hae III restriction enzyme
      fragments. Dengue-2 virus exists as two topotypes in the region with apparently
      non-overlapping distributions. The Puerto Rico topotype, which has been in the
      Caribbean for at least 40 years, is genetically diverse, while the Jamaica
      topotype, first isolated in 1981, is more homogeneous and has expanded its range
      from the original Caribbean focus to South America.

PMID- 7516148
TI  - Granulomatous reaction to Bruch's membrane in age-related macular degeneration.
AB  - The histopathologic features of a granulomatous reaction in one eye of a patient
      with neovascular age-related macular degeneration are presented. Multiple
      multinucleated giant cells were found in intimate association with Bruch's
      membrane and at the margin of Bruch's membrane defects. Multinucleated giant
      cells appear to participate in the breakdown of Bruch's membrane and, together
      with diffuse disease of the retinal pigment epithelium and changes in the
      physicochemical properties of Bruch's membrane, may provide angiogenic stimulus
      for choroidal neovascularization in age-related macular degeneration.

PMID- 7516150
TI  - Operant extinction in the treatment of severe maladaptive behavior: adapting
      research to practice.
AB  - Operant extinction involves termination of reinforcement for a previously
      reinforced response. As a clinical intervention for severe maladaptive behavior
      operant extinction is often repudiated because of intensity of side effects,
      length of treatment time required, and implementation difficulties. This article
      discusses both theoretical and practical aspects of extinction, including
      components of the extinction process and the importance of functional assessment
      to its effective use. Potential strategies for increasing the effectiveness of
      extinction while diminishing intrusiveness are recommended. Based on recent
      research innovations, a technology is emerging for effective use of operant
      extinction in the treatment of severe maladaptive behavior.

PMID- 7516149
TI  - Identification and genotyping of hepatitis C virus in injectable and oral drug
      users in New Zealand.
AB  - BACKGROUND: Hepatitis C virus infections are known to be common in injectable
      drug users (IDU) both in New Zealand and overseas. Little is known of the
      hepatitis C genotype frequency in this population. AIMS: To confirm the high
      incidence of hepatitis C virus infections in IDU and compare this with the
      frequency in oral drug users (ODU) as well as identify the pattern of hepatitis C
      genotypes present. METHODS: Use was made of an experimental nucleocapsid assay as
      well as a conventional anti-HCV assay. HCV-RNA was identified using a polymerase
      chain reaction (PCR) technique and a variation of this method was used for HCV
      genotyping. RESULTS: Seventy-four per cent of IDU were reactive for anti-HCV in
      both types of assay. PCR testing detected several more reactive samples. Dominant
      genotypes were Types I and V, but Type IV was not detected. Mixed infections were
      noted in some patients. There was a low frequency of anti-HCV in ODU.
      CONCLUSIONS: Hepatitis C virus infections are a problem in IDU in New Zealand,
      and additional public health measures may be required. The distribution of
      genotypes of HCV-RNA are similar to those seen in other Western countries.

PMID- 7516154
TI  - Reconstitution of proteolipid protein: some properties and its role in
      interlamellar attachment.
AB  - Proteolipid apoprotein (PLP) isolated from human brain was reconstituted in
      dioleoylphosphatidylcholine vesicles by dialysis from 2-chloroethanol, using a
      dialysis buffer of pH 5.0. Under these conditions, and in contrast with dialysis
      carried out at pH 7.4, well-defined unilamellar vesicles containing the protein
      were formed. As judged by electron microscopy and quasi-elastic light scattering,
      the size of the vesicles was determined by the initial protein/lipid ratio used
      for reconstitution. When the vesicles were incubated in a buffer at neutral pH,
      aggregation of the vesicles was observed, but their structure remained intact.
      Asymmetric aggregation occurred when the reconstituted vesicles were incubated
      with large unilamellar vesicles (LUVs) devoid of protein. This aggregation was
      accompanied by loss of membrane integrity, as revealed by extensive leakage of
      the LUVs, and by membrane lipid dilution, indicative of the occurrence of
      membrane fusion. Destabilization of the vesicles depended on the presence of
      negatively charged phosphatidylserine in the membrane of the LUVs. Similar
      effects, but to a lesser extent, were seen when the LUVs contained sulphatide, a
      negatively charged lipid prominently present in myelin. DM 20, a natural mutant
      of PLP, appeared to be far less potent in causing membrane lipid dilution than
      PLP. This could suggest that a distinct protein sequence of PLP, which is absent
      from DM 20, may be involved in triggering the observed membrane destabilization.
      Temperature-dependent experiments indicate that this sequence in PLP displays
      dynamic properties, its exposure being affected by conformational criteria.
      Exposure of this particular domain, in conjunction with its affinity for
      negatively charged lipid, could be related to a perturbation of the integrity of
      the myelin sheath, as will be discussed.

PMID- 7516155
TI  - Antisense src expression inhibits U937 human leukemia cell proliferation in
      conjunction with reduction of c-myb expression.
AB  - To elucidate the role of pp60c-src in U937 human monoblastoid leukemia cell
      proliferation, recombinant plasmids containing the src gene or myb gene, which
      could produce antisense src or antisense myb RNA after dexamethasone treatment,
      were constructed and transfected into U937 cells (U937-ASRC, U937-AMYB). pp60c
      src synthesis in U937-ASRC was diminished by the third day after induction of
      antisense src RNA and the cell proliferation was reduced, furthermore, the amount
      of p75c-myb was significantly decreased by the third day. p75c-myb synthesis in
      U937-AMYB was diminished by the second day after induction of antisense myb RNA
      and the cell growth was significantly inhibited but the amount of pp60c-src in
      U937-AMYB was not reduced. These results suggest that a decrease in the amount of
      pp60c-src leads to an inhibition of p75c-myb expression and subsequent reduction
      in the U937 cell proliferation.

PMID- 7516151
TI  - Hydrodynamic and pharmacological characterization of putative alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-sensitive L-glutamate
      receptors solubilized from pig brain.
AB  - L-[3H]Glutamate binding sites with characteristics resembling that of membrane
      bound alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate
      subtype L-glutamate receptors have been solubilized from pig brain synaptic
      junctions by Triton X-114. Binding of [3H]AMPA to these soluble sites in the
      presence of KSCN results in a curvilinear Scatchard plot that can be resolved
      into a high-affinity component and a low-affinity component. These Triton-X-114
      solubilized sites can be further separated into two species of binding sites by
      gel-filtration chromatography or sucrose-density-gradient centrifugation. The
      pharmacological profiles of these two species of binding site are almost
      identical, and the rank orders of potency for glutamatergic drugs in displacing L
      [3H]glutamate binding to these sites are quisqualate > 6,7-dinitroquinoxaline-2,3
      dione > 6-cyano-7-nitroquinoxaline-2,3-dione > AMPA > L-glutamate > kainate >> N
      methyl-D-aspartate = L-2-amino-4-phosphonobutyrate. Both sites are found to bind
      [3H]AMPA, and in the presence of KSCN the binding activities are significantly
      enhanced. Analysis of the hydrodynamic behaviour of these binding sites by
      sucrose-density-gradient centrifugation in H2O- and 2H2O-based solvents and gel
      filtration chromatography has revealed that one of these sites (Stokes radius 8.3
      nm, sedimentation coefficient 18.5 S) consists of 562 kDa protein and 281 kDa
      detergent, and the other site (Stokes radius 9.6 nm, sedimentation coefficient
      13.4 S) consists of 352 kDa protein and 569 kDa detergent. Frictional
      coefficients of these sites indicate that these receptor-detergent complexes are
      asymmetrical in structure, consistent with large transmembrane proteins.

PMID- 7516153
TI  - Binding of lipoprotein lipase to alpha 2-macroglobulin.
AB  - The interaction between bovine lipoprotein lipase (bLPL) and human alpha 2
      macroglobulin (alpha 2M) was studied by use of non-denaturing PAGE and gel
      permeation, Zn(2+)-Sepharose and heparin-Sepharose chromatography. It was
      demonstrated that bLPL in vitro binds non-covalently to native alpha 2M, but not
      to the receptor-recognized form produced by treatment of alpha 2M with
      chymotrypsin or methylamine. A small amount of bLPL was bound covalently to alpha
      2M by disulphide interchange, when incubated together with chymotrypsin or
      methylamine. Whereas alpha 2M in complex with bLPL still bound to Zn(2+)
      Sepharose, bLPL lost the ability to bind to heparin-Sepharose. Preincubation of
      bLPL with heparin prevented complex-formation with alpha 2M, suggesting that
      alpha 2M interacts with the heparin-binding domain of bLPL. Experiments in which
      125I-bLPL was incubated with human plasma at 20 degrees C demonstrated an 11-17%
      binding of the labelled lipase to alpha 2M, indicating that this interaction may
      be of physiological significance.

PMID- 7516152
TI  - Structural and functional characterization of elastases from horse neutrophils.
AB  - In order better to understand the pathophysiology of the equine form of
      emphysema, two elastinolytic enzymes from horse neutrophils, referred to as
      proteinases 2A and 2B, have been extensively characterized and compared with the
      human neutrophil proteinases, proteinase-3 and elastase. Specificity studies
      using both the oxidized insulin B-chain and synthetic peptides revealed that
      cleavage of peptide bonds with P1 alanine or valine residues was preferred.
      Further characterization of the two horse elastases by N-terminal sequence and
      reactive-site analyses indicated that proteinases 2A and 2B have considerable
      sequence similarity to each other, to proteinase-3 from human neutrophils
      (proteinase 2A), to human neutrophil elastase (proteinase 2B) and to a lesser
      extent to pig pancreatic elastase. Horse and human elastases differed somewhat in
      their interaction with some natural protein proteinase inhibitors. For example,
      in contrast with its action on human neutrophil elastase, aprotinin did not
      inhibit either of the horse proteinases. However, the Val15, alpha-aminobutyric
      acid-15 (Abu15), alpha-aminovaleric acid-15 (Nva15) and Ala15 reactive-site
      variants of aprotinin were good inhibitors of proteinase 2B (Ki < 10(-9) M) but
      only weak inhibitors of proteinase 2A (Ki > 10(-7) M). In summary, despite these
      differences, the horse neutrophil elastases were found to resemble closely their
      human counterparts, thus implicating them in the pathological degradation of
      connective tissue in chronic lung diseases in the equine species.

PMID- 7516157
TI  - Concentration of serum amyloid P component in the CSF as a possible marker of
      cerebral amyloid deposits in Alzheimer's disease.
AB  - Serum amyloid P component (SAP) is a normal plasma protein produced in the liver
      and co-deposited with amyloid fibrils in all types of amyloidosis, including
      cerebral beta-protein amyloid deposits associated with Alzheimer's disease (AD).
      We have measured its concentration and those of alpha 2-macroglobulin, IgG and
      albumin in the CSF of 51 patients with AD and 50 healthy and disease control
      subjects. The mean levels of SAP were 12.8 ng/ml in AD and 8.5 ng/ml in controls
      (P < 0.0125); there was no difference in the levels of the other proteins
      studied. The observed concentrations of SAP were much lower than expected for a
      protein of molecular weight 254620. The difference between AD and controls
      suggests that the concentration of SAP in the CSF may be affected by the presence
      of cerebral amyloidosis.

PMID- 7516156
TI  - Appearance of a novel Ca2+ influx pathway in Sf9 insect cells following
      expression of the transient receptor potential-like (trpl) protein of Drosophila.
AB  - Activation of phospholipase C, elevation of free cytosolic Ca2+ concentration
      ([Ca2+]i) and stimulation of Ca2+ influx have been implicated in Drosophila
      phototransduction. Electrophysiological studies suggest that trp and trpl
      proteins may be important for the light-activated Ca2+ current found in
      Drosophila photoreceptor cells. Although these proteins exhibit homologies to
      voltage-gated Ca2+ and Na+ channels, their actual function in insect cells and
      their relation to proteins involved in mammalian cell Ca2+ signaling remains
      unknown. In the present study, [Ca2+]i was examined in fura-2-loaded Sf9 insect
      cells infected with recombinant baculovirus containing cDNA for the trpl protein.
      Ca2+ influx was examined by use of Ba2+, a Ca2+ surrogate that is not a substrate
      for Ca(2+)-pumps or carriers and by measurement of whole-cell membrane currents.
      The results suggest that expression of trpl is associated with appearance of a
      Ca2+ permeable, non-selective cation channel formed by the trpl protein.

PMID- 7516158
TI  - Nitric oxide limits transcriptional induction of nitric oxide synthase in CNS
      glial cells.
AB  - Nitric oxide (NO) can modulate directly and indirectly the activity of a variety
      of enzymes, including nitric oxide synthase (NOS). In addition, it appears that
      the NO formed by astroglial cells in which transcriptional induction of NOS has
      been evoked by cytokines affects NOS mRNA level. We have observed that induction
      in the presence of NOS inhibitors or NO-trapping agents amplifies NOS mRNA
      expression and that this effect is reversed by an NO donor. Rather than promoting
      mRNA instability, NO appears to inhibit the transcriptional induction of NOS.
      This effect of NO on induction of the NOS gene provides a mechanism by which the
      temporal and perhaps spatial production in the nervous system of NO, a reactive
      and potentially toxic mediator, can be finely regulated.

PMID- 7516159
TI  - Cloning and expression kinetics of porcine vascular cell adhesion molecule.
AB  - Human vascular cell adhesion molecule is believed to play a key role in
      recruiting leukocytes to sites of injury. Here we report the identification of a
      homologous molecule in the pig which has five Ig domains and an overall 77%
      homology with the human protein. The expression of this protein was also
      characterised on porcine endothelial cells. Like the human adhesion molecule, the
      porcine protein could be induced by LPS, TNF and IL-1 alpha, although differences
      were noted in the kinetics of expression.

PMID- 7516160
TI  - Protein tyrosine phosphorylation triggered by human Fc gamma RII.
AB  - The role of the cytoplasmic domain of human Fc gamma RII in cellular activation
      was studied by transfecting P815 cells with different isoforms or deletion
      mutants of this receptor and then assaying protein tyrosine phosphorylation after
      crosslinking with anti-CD32 monoclonal antibodies. Fc gamma RIIa, but not Fc
      gamma RIIb1 or b2, was able to trigger tyrosine phosphorylation. Deletion of just
      the carboxyl-terminal 19 amino acids of Fc gamma RIIa markedly reduced induction
      of protein tyrosine phosphorylation. Deletion of the carboxyl-terminal 38 amino
      acids of the cytoplasmic domain completely eliminated this response. These
      results indicate the cytoplasmic domain of human Fc gamma RIIa, the form of Fc
      gamma RII that predominates on human myeloid cells and platelets, contains
      sequences that allow activation of tyrosine phosphorylation; Fc gamma RIIb
      isoforms, the form of Fc gamma RII on human B lymphocytes, lack these sequences.

PMID- 7516161
TI  - Increase of phosphotyrosine levels in mouse urine and liver during liver
      regeneration after partial hepatectomy.
AB  - To determine how cell proliferation contributes to phosphotyrosine (P-Tyr) level
      in body we investigated the changes of P-Tyr levels in mouse urine and liver
      during liver regeneration after partial hepatectomy (PH). After PH, the P-Tyr
      contents in urine and liver increased approximately 14- and 1.7-fold,
      respectively, at 2-4 days, and P-Tyr phosphatase activity in liver decreased to
      50% at 2 days. These levels returned to the control level at 10 days. After
      orthovanadate administration, P-Tyr level increased as P-Tyr phosphatase activity
      decreased. These results suggest that P-Tyr level in liver is reflected in
      urinary P-Tyr level during liver regeneration, and P-Tyr phosphatase is important
      in the regulation of P-Tyr level.

PMID- 7516163
TI  - Evidence for loss of apo B from LDL in human atherosclerotic lesions:
      extracellular cholesteryl ester lipid particles lacking apo B.
AB  - Previous studies have demonstrated the accumulation of low density lipoprotein
      (LDL) in the extracellular spaces of the intima of normal and atherosclerotic
      human vessels. In this study we have assessed the degree of colocalization in
      vessels of apolipoprotein B (apo B), the major protein of LDL, with cholesteryl
      ester, the predominant lipid of LDL. Apo B was detected immunohistochemically and
      cholesteryl ester was detected after its enzymatic hydrolysis and staining with
      the fluorescent probe, filipin. Most normal intima showed apo B staining without
      associated cholesteryl ester staining. This result would be expected with LDL
      having intact apo B; intact apo B interferes with hydrolysis and filipin staining
      of LDL cholesteryl ester. Fatty streaks and fibrous plagues showed regions of
      congruent apo B and cholesteryl ester staining in the extracellular space,
      suggesting fragmentation of apo B without loss of its immunoreactivity. Still
      other areas of lesions showed cholesteryl ester staining in the extracellular
      space without apo B staining. This staining pattern suggests loss of apo B from
      LDL leaving only the cholesteryl ester-rich core of LDL. Progressive loss of apo
      B from LDL can explain the patterns of apo B and cholesteryl ester colocalization
      that occur in vessel wall intima. The distribution of these patterns in normal
      and atherosclerotic lesions suggests that loss of apo B from the cholesteryl
      ester core of LDL is associated with lesion development.

PMID- 7516162
TI  - Expression of ICAM-R (ICAM-3), a novel counter-receptor for LFA-1, in rheumatoid
      and nonrheumatoid synovium. Comparison with other adhesion molecules.
AB  - OBJECTIVE: To study the distribution of intercellular adhesion molecule receptor
      (ICAM-R, or ICAM-3), a novel ligand for the leukointegrin lymphocyte function
      associated antigen 1 (LFA-1), in normal and rheumatoid synovial membranes and to
      compare this with the distribution of ICAM-1, ICAM-2, vascular cell adhesion
      molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1).
      METHODS: We performed immunohistochemical analyses of frozen sections of normal
      and rheumatoid synovial tissue using monoclonal antibodies to the molecules
      examined. RESULTS: ICAM-1 staining was detectable on the vascular endothelium and
      the synovial lining cells of both normal and rheumatoid synovial membranes. A
      variable proportion of lymphocytes infiltrating rheumatoid tissues expressed ICAM
      1, ICAM-2 staining was demonstrable in the vascular endothelium of both normal
      and inflamed tissues, the latter demonstrating a significantly higher proportion
      of positive vessels. ELAM-1 staining was not detectable in normal synovial
      membranes but was seen on the endothelium of a limited number of rheumatoid
      synovial vessels, usually close to the synovial lining cell layer. VCAM-1
      staining was intense in both normal and rheumatoid synovial lining cells, but
      vascular staining was weak in both. In contrast, ICAM-R staining was not detected
      in association with any synovial blood vessels, but was widely expressed by
      lymphocytes and macrophages. Cells of the lining layer did not stain for ICAM-R.
      CONCLUSION: Although ICAM-R is a ligand for LFA-1 and shares considerable
      sequence homology with ICAM-1 and ICAM-2, it does not appear to be expressed by
      the endothelium of normal or inflamed synovial vessels. Intense expression of
      ICAM-R by rheumatoid synovial lymphocytes and macrophages suggests that it may
      play a role in processes requiring cell-cell contact, such as antigen
      presentation and homotypic aggregation.

PMID- 7516164
TI  - Studies on capillarization of the hepatic sinusoids in alcoholic liver disease.
AB  - It has been reported that basement membranes were found around the sinusoidal
      walls in cirrhotic livers, indicating the development of capillarization of the
      sinusoids. It has been also emphasized that capillarization of the sinusoids is
      more prominent in alcoholic liver disease (ALD). In the present study, factor
      VIII related antigen (VIII-Ag) and UEA-1 were identified immunohistochemically in
      order to analyze capillarization of the sinusoids in chronic liver diseases.
      Electron microscopic studies on the endothelial cells and sinusoids were also
      performed. Electron microscopic studies revealed that the number of fenestra in
      the endothelial cells decreased and basement membranes were clearly observed in
      the space of Disse from an early stage of ALD. However, these changes were not
      observed in the early stage of non-ALD. VIII-Ag or UEA-1 was not stainable in the
      sinusoidal cells of normal livers or at an early stage of non-ALD. However, in
      ALD, both VIII-Ag and UEA-1 were clearly demonstrated in the sinusoidal cells
      from the early stage of fibrosis. These results suggest that the sinusoidal
      endothelial cells may transform to vascular endothelial cells from an early stage
      of ALD. The alterations in the sinusoidal endothelium and the basement membrane
      formation in the Disse space indicate that capillarization of the sinusoid may
      occur. Capillarization of the sinusoid may cause a disturbance in exchanges of
      many bioactive substances between the sinusoidal blood and hepatocytes across the
      Disse space and may thereby contribute to the pathogenesis of ALD.

PMID- 7516165
TI  - Supplemental instruction: increasing student performance and persistence in
      difficult academic courses.

PMID- 7516166
TI  - Synthesis and muscarinic receptors affinity of a series of antagonist bivalent
      ligands.
AB  - A series of bivalent ligands (2-8) derived from 2,2-diphenyl-[1,3]-dioxolan-4
      ylmethyl-dimethylamine methiodide 1 has been synthesized and tested to evaluate
      affinity and selectivity for M1, M2 and M3 muscarinic receptor subtypes. In order
      to study the contribution of the spacer and of a second cationic head to the
      binding process, unsymmetrical ligands (9,10) have also been prepared. The
      results, expressed in terms of pA2 values, show that, although the spacer
      negatively affects the interaction of the bivalent ligands with the three
      receptor subtypes, affinity and selectivity are modulated by its length; this
      indicates that the pharmacophore binding sites are organized differently with
      respect to their mutual proximity and orientation, in each receptor subtype.

PMID- 7516167
TI  - Unilateral AMPA lesions of nucleus basalis magnocellularis induce a sensorimotor
      deficit which is differentially altered by arecoline and nicotine.
AB  - One week after unilateral alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid (AMPA) lesions of nucleus basalis magnocellularis, rats showed significant
      lateralised bias in spontaneous turning and in turning induced by tail pinch or
      by placing the rat on a 45 degrees grid. Turning was biased to the lesioned side
      and this side also showed increased responsiveness to pin-prick stimulation of
      the skin (somaesthesia), snout and whisker stimulation and ammonia olfaction.
      Arecoline (0.5 mg/kg), at a dose which did not affect responses to sensorimotor
      stimulation in sham-operated rats, corrected the lesion-induced biased turning to
      tail pinch and the 45 degrees grid test and reduced the bias in the open field.
      In contrast, nicotine (0.05 mg/kg), at a dose which also did not substantially
      affect responses to sensorimotor stimulation in sham-operated rats, switched the
      lesion-induced turning bias towards the contralateral side. Neither cholinoceptor
      agonist reduced the lesion-induced increased sensory responsiveness. The effects
      of nicotine were blocked by the centrally acting nicotinic antagonist,
      mecamylamine (1.0 mg/kg), but not by hexamethonium (1.0 mg/kg), or ondansetron
      (0.01 mg/kg). Amphetamine (up to 1.0 mg/kg) did not affect the lesion-induced
      motor asymmetry. The results confirm that the basal forebrain cholinergic system
      plays a role in sensorimotor cortical functions, but suggest different functional
      roles for muscarinic and nicotinic receptors.

PMID- 7516168
TI  - The Escherichia coli ribosomal RNA leader: a structural and functional
      investigation.
AB  - The structure of the E. coli ribosomal RNA leader was analyzed by treatment with
      single and double strand specific ribonucleases and by chemical modification. The
      experimentally derived data together with secondary structure calculations
      according to minimum free energy was used to construct a secondary structure
      model. The binding of purified Nus proteins to the ribosomal leader RNA was
      further tested. Contrary to the recently reported interactions of NusB and NusE
      with a nut RNA sequence we obtained evidence that the presence of NusA and NusE
      resulted in protection against hydroxyl radical reaction of the leader nut
      elements boxA, boxB and boxC. The possible significance of this interaction is
      discussed. In the second part of the study we analyzed effects of leader
      mutations, which are known to affect cell growth, on the activity of ribosomes in
      vivo. A system was used able to distinguish the proportion of ribosomes assembled
      from rRNA of chromosomal origin (wild type) and plasmid origin (mutant). It
      turned out that the amount of 16S RNA transcribed from genes with point mutations
      in the leader region decreased if ribosomal pools with different translational
      activities were compared. High amounts of transcripts from mutant operons were
      present in the free ribosomal RNA and the free 30S fractions. Significantly less
      16S RNA transcripts from the mutated genes were detected in the functionally
      active and homogeneous 70S tight couple preparations, and even less in the
      polysome fraction involved in active translation. The results allow a better
      understanding of the function of rRNA leader sequences in structure formation and
      correct ribosome biogenesis.

PMID- 7516169
TI  - Induction of intercellular adhesion molecule 1 expression on normal human
      keratinocytes by retinoic acid: comparison of cultured keratinocytes and skin
      explants.
AB  - As retinoic acid (RA, all trans) induces irritant reactions when applied
      topically to skin, we wondered whether it may be involved in the activation state
      of keratinocytes through ICAM-1 induction. Human skin explants and cultured
      keratinocytes were treated by RA and/or interferon-gamma (IFN gamma) at different
      concentrations during 24, 48 and 72 h. ICAM-1 expression was examined and
      quantified by immunohistochemistry, in situ, on cutaneous frozen sections and in
      cultured keratinocytes by flow cytometry analysis. Expression of mRNA was checked
      by Northern blot hybridizations using an oligonucleotide probe. Our results
      indicate: (1) the absence of spontaneous ICAM-1 expression by normal human
      keratinocytes both in skin explants and in cultures; (2) an ICAM-1-induced
      expression after 48 h of treatment by RA concentrations > 10(-6) M; this
      induction is dose- and time-dependent; in skin explants, ICAM-1 is occasionally
      observed on foci of epidermal cells; this protein induction is correlated with
      transcript expression in cultured keratinocytes; and (3) a synergistic effect of
      RA and IFN gamma (5 IU/ml) on the percentage of ICAM-1-positive cells and the
      level of expression of the protein. These findings indicate that RA, in a
      therapeutical range of concentrations can induce or stimulate ICAM-1 expression
      in normal human keratinocytes. This may in part explain the erythematous reaction
      observed in vivo after topical applications of RA which may be considered as a
      mediator of keratinocyte activation.

PMID- 7516170
TI  - High-frequency sonophoresis: permeation pathways and structural basis for
      enhanced permeability.
AB  - The mechanism of stratum corneum (SC) permeabilization by ultrasound
      (sonophoresis) is unknown. We studied here permeation pathways, and SC
      intercellular structural organization following applications of high-frequency
      sonophoresis to hairless mouse skin. Ruthenium tetroxide post-fixation and tracer
      solutions of LaNO3 and FITC-dextrans were employed to examine SC lamellar
      bilayers, lamellar body morphology and subcellular permeation pathways.
      Sonophoresis disrupted the compact organization of SC bilayers and LB-derived
      contents at the stratum granulosum (SG)-SC interface, leading to domain
      separation between 0 and 20 h, reverting by 48 h. Post-sonophoresis, tracers
      traversed the SC via lacunae within the lamellar bilayers, and via lamellae in
      sites that displayed domain separation. These studies provide insights about the
      penetration pathways, permeabilizing mechanisms, and kinetics of sonophoresis on
      the epidermis.

PMID- 7516171
TI  - Culture of pulmonary microvascular smooth muscle cells from intraacinar arteries
      of the rat: characterization and inducible production of nitric oxide.
AB  - Pulmonary arterial microvascular smooth muscle function governs many aspects of
      lung physiology and pathophysiology. Acutely, microvascular smooth muscle cells
      (SMC) modulate pulmonary vascular resistance; chronically, they contribute to
      vascular remodeling. Recent work has also suggested a possible immune function
      for pulmonary smooth muscle through cytokine-stimulated nitric oxide production.
      To facilitate study of the mechanisms underlying these functions, we have
      developed methods for isolating pulmonary arterial microvessels from the rat and
      culturing SMC from these vessels. The pulmonary arterial circulation was filled
      with a suspension of iron oxide in agar, and a subpleural tissue sample was
      obtained. The vessels were cleared of surrounding lung parenchyma by partial
      collagenase digestion, and the iron-containing arteries were separated
      magnetically. The diameter of the harvested arteries confirmed an intraacinar
      origin, and the cultured cells expressed smooth muscle isoforms of alpha-actin
      and myosin but did not take up acetylated low density lipoprotein. To assess a
      possible immune effector role for these cells, confluent monolayers were
      stimulated with cytokines and endotoxin. At 24 h, immunofluorescent staining for
      inducible nitric oxide synthase was prominent within these cells. Nitric oxide
      production, as measured by nitrite levels in the cell-conditioned medium, was
      also markedly elevated but reduced by adding NG-monomethyl-L-arginine. We
      conclude that rat pulmonary arterial microvascular SMC can be obtained by the
      iron oxide infusion method and that these cells express an inducible nitric oxide
      synthase after cytokine stimulation.

PMID- 7516172
TI  - Hypertrophic and hyperplastic changes of mucus-secreting epithelial cells in rat
      airways: assessment using a novel, rapid, and simple technique.
AB  - Determination of hyperplastic and hypertrophic changes of mucus-secreting cells
      in animal airways has been performed in the past by using histologic,
      immunologic, and/or molecular biologic approaches. Histologic techniques are
      tedious and time-consuming. The other approaches require specific antibodies and
      cDNA probes that have proved difficult to develop. Described here is a method for
      the rapid estimation of hyperplastic and hypertrophic changes of secretory
      epithelial cells in rat airways. The assay specifically measures acidic and
      neutral mucoproteins in a linear fashion from 0.5 microgram to at least 10
      micrograms. Male Sprague-Dawley rats were exposed to metabisulfite mist (10%
      wt/vol) for 5 days/wk for 3 wk. The lungs were removed and homogenized in a
      phosphate-buffered solution containing reducing agents and protease inhibitors.
      The particulate matter was removed by centrifugation, and the soluble extract was
      applied to a column packed with Sepharose CL-6B. The material eluting in the void
      volume was applied to a PVDF membrane and stained for either acidic or neutral
      mucosubstances using Alcian blue or periodic acid-Schiff (PAS) staining, and the
      absorbance was read using a 96-well plate reader. Lungs from sodium metabisulfite
      exposed animals showed a 7-fold and 3.5-fold increase in PAS-positive and Alcian
      blue-positive material, respectively. The increase in both PAS and Alcian blue
      staining was hyaluronidase and chondroitinase insensitive. The observed changes
      are consistent with morphometric measurements of mucus-containing cells in
      histologic sections of the tissues. This assay may be useful in determining which
      neurohumoral mediators might be involved in mucus cell hypertrophy and
      hyperplasia in animal models of chronic obstructive pulmonary disease.

PMID- 7516174
TI  - Coordinated expression of a 45 kD protein and ozone toxicity in a human bronchial
      epithelial cell line.
AB  - The human bronchial epithelial cell line, BEAS-2B, which was immortalized by
      transformation with SV40 virus, when grown biphasically between 0.1 and 1.0 ppm
      of ozone and liquid medium showed increased release of Cr, decreased synthesis of
      various macromolecules, and decreased cell viability. Cell injury was a function
      of the concentration of ozone to which the cells were exposed. Furthermore, in
      proportion to the extent of cell injury, ozone exposure also induced and/or
      enhanced synthesis of a 45 kD protein but not any of the well-characterized heat
      shock proteins, e.g., HSP 70. Actinomycin D prevented enhanced synthesis of the
      45 kD protein in cells exposed to ozone, suggesting transcriptional regulation of
      expression of the 45 kD protein. Enhanced synthesis of the 45 kD protein was not
      observed in cells treated with heat, cigarette smoke condensate, hydrogen
      peroxide, or bleomycin. High concentrations of glutathione added to the culture
      medium reduced ozone toxicity and ozone-enhanced synthesis of the 45 kD protein.
      These results suggest that ozone injury and enhanced expression of a gene
      encoding a 45 kD protein of as yet unknown function are coordinated in the SV40
      immortalized bronchial epithelial cells.

PMID- 7516175
TI  - Endocytosis of integrin alpha 5 beta 1 (fibronectin receptor) of mouse peritoneal
      macrophages in vitro: an immunoelectron microscopic study.
AB  - Localization and dynamic aspects of fibronectin receptor (alpha 5 beta 1
      integrin) were investigated by immunoelectron microscopy on freshly isolated
      mouse peritoneal macrophages and after cultivation in vitro. This receptor has
      only been characterized biochemically. Identity of macrophages was proved by
      binding of the antibody against the F4/80 specific macrophage marker.
      Demonstration of fibronectin receptor and mouse macrophage marker on the plasma
      membrane revealed that these glycoproteins were rapidly endocytosed within the
      first minutes after isolation. Endocytotic uptake of these glycoproteins was
      demonstrated by double immunolabeling and secondary labeling with gold particles
      of different size. Label was found in endocytotic and lysosome-like vesicles, but
      not in coated vesicles. During further cultivation the macrophage marker
      reappeared again on the plasma membrane after 3 hr, but the fibronectin receptor
      was not demonstrable. Treatment with cytochalasin B in culture and incubation at
      4 degrees C resulted in strongly labeled plasma membrane and inhibition of
      internalization. In contrast to macrophages, alpha 5 beta 1 integrin was
      demonstrable on marmoset skin fibroblasts even after 3 days in culture. In this
      cell type, endocytotic uptake was solely detectable in coated vesicles. These
      results suggest a high endocytotic activity of macrophages after isolation
      leading to a rapid disappearance of both glycoproteins, whereby, in contrast to
      the fibronectin receptor, only the macrophage marker is recycled again. These
      data indicate a change in plasma membrane (receptor content) after isolation and
      cultivation of macrophages and cell-specific differences in vitro.

PMID- 7516173
TI  - Glucocorticoid inhibition of interleukin-1-induced interleukin-6 production by
      human lung fibroblasts: evidence for transcriptional and post-transcriptional
      regulatory mechanisms.
AB  - Interleukin (IL)-6 is a pleiotropic cytokine produced by a wide variety of cells
      including fibroblasts, macrophages, endothelial cells, and T and B lymphocytes.
      Regulated IL-6 production is an important part of normal biologic homeostasis,
      and abnormal IL-6 production has been associated with a large number of diseases
      including asthma and lung allograft rejection. Glucocorticoids are potent anti
      inflammatory agents that are widely used to suppress pulmonary inflammation. To
      further understand the mechanisms underlying this inhibition, we determined
      whether glucocorticoid compounds regulate human lung fibroblast IL-6 production
      and characterized the mechanisms of the effects that were noted. These studies
      demonstrate that glucocorticoids inhibit IL-1-induced IL-6 production in a dose
      dependent fashion. A greater than 95% decrease in IL-6 production was seen with
      10(-6) and 10(-7) M dexamethasone, prednisolone, and hydrocortisone, and IC50
      values for these agents were approximately 5 x 10(-10), 5 x 10(-9), and 10(-8) M,
      respectively. mRNA analysis demonstrated that these alterations in protein
      production were associated with proportionate decreases in IL-6 mRNA
      accumulation, and that this suppression of IL-6 mRNA could be reversed by the
      glucocorticoid receptor antagonist RU 486. Nuclear run-on studies demonstrated
      that glucocorticoids inhibit-IL-1-induced IL-6 gene transcription. However, the
      magnitude of this effect could not fully account for the potency of the
      glucocorticoid-induced alterations in IL-6 mRNA accumulation and protein
      production since 10(-6) M dexamethasone caused only a 50% decrease in IL-1
      induced IL-6 gene transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516176
TI  - The sublaminar organization of corticogeniculate neurons in layer 6 of macaque
      striate cortex.
AB  - We examined the laminar distribution of corticogeniculate neurons in the macaque
      striate cortex labeled by axonal transport following injections of retrograde
      tracers into the lateral geniculate nucleus (LGN). Large injections of retrograde
      tracers involving all layers of the LGN resulted in a distinctive bilaminar
      distribution of labeled cells in cortical layer 6. One tier of labeled neurons
      was located along the layer 5-6 border and a second was located near the bottom
      of the layer, leaving the middle of layer 6 largely free of labeled neurons.
      Following injections of tracers that were restricted to the magnocellular layers
      of the LGN, almost all of the labeled neurons were located in the lower tier. In
      contrast, following injections of retrograde tracers confined to the
      parvocellular layers of the LGN, labeled cells were found in both tiers, with the
      greatest number in the upper tier. Thus, layer 6 of macaque striate cortex
      consists of three distinct sublayers only two of which are the source of
      descending projections to the LGN: an upper tier that projects exclusively to the
      parvocellular layers and a lower tier that projects to both magnocellular and
      parvocellular layers.

PMID- 7516178
TI  - Localization of substance P and GABA in retinotectal ganglion cells of the larval
      tiger salamander.
AB  - The present study was performed as part of a systematic examination of the
      transmitter specificity of neuronal populations in the larval tiger salamander
      retina. Backfill-labeling of ganglion cells from the optic tectum was combined
      with double-label immunofluorescence histochemistry to determine if substance P
      and GABA are localized to ganglion cell populations in the tiger salamander
      retina. The triple-label analysis revealed the presence of substance P- and GABA
      ganglion cells in both central and peripheral regions of the retina. Substance P
      immunoreactive ganglion cells comprised 2% of the total population of backfill
      labeled ganglion cells, while less than 1% of backfill-labeled ganglion cells
      expressed GABA immunoreactivity. Ganglion cells were not found to co-label for
      both substance P and GABA. Backfill-labeled displaced ganglion cells, which
      comprised 1.4% of the ganglion cell population, were not observed to be
      immunoreactive for either substance P or GABA. Forty-six point nine percent of
      substance P-cells in the ganglion cell layer were backfill-labeled and were
      identified as ganglion cells. GABA ganglion cells comprised less than 1% of GABA
      immunoreactive cells in the ganglion cell layer. Therefore, the present study
      provides evidence for the presence of small populations of substance P- and GABA
      ganglion cells in the larval tiger salamander retina. These observations suggest
      a functional diversity in the population of tiger salamander ganglion cells
      relative to their unique transmitter specificities.

PMID- 7516177
TI  - Reciprocal connections between the rabbit suprageniculate pretectal nucleus and
      the superior colliculus: tracer study with horseradish peroxidase and fluorogold.
AB  - Connections of the rabbit suprageniculate pretectal nucleus (SP) with the
      superior colliculus were explored by means of retrograde transport of horseradish
      peroxidase or Fluorogold. Large injections centered in the superficial and
      intermediate tectal layers resulted in bilateral retrograde transport to the
      medium-size multipolar neurons of the suprageniculate pretectal nucleus.
      Horseradish peroxidase was also transported anterogradely into the ipsilateral
      and contralateral neuropiles of the suprageniculate pretectal nucleus. The
      labeled cells in SP were dispersed throughout the nucleus, including its dorsal,
      wedge-shaped, internal portion. Labeling was mainly ipsilateral, and less
      abundant on the contralateral side.

PMID- 7516179
TI  - Voltage-gated currents of rabbit A- and B-type horizontal cells in retinal
      monolayer cultures.
AB  - In monolayer cultures prepared from immature early postnatal rabbit retina, small
      populations of neurons can be demonstrated to differentiate into apparently
      mature A- and B-type horizontal cells. Using whole-cell, single-channel, patch
      clamp recording techniques, we have analyzed the pattern of voltage-gated
      conductances expressed by mammalian horizontal cells under these conditions. A
      total of six different voltage-dependent ionic currents were recorded.
      Tetrodotoxin-sensitive fast sodium inward currents (INa) were found in 81% of the
      A-type and 90% of the B-type cells. Inward calcium currents could be demonstrated
      in all cells tested after blockade of other conductances. Two types of outward
      potassium currents with properties of the 4-aminopyridine-sensitive transient IA
      and the tetraethylammonium sensitive delayed rectifier IK, respectively, could be
      characterized in whole-cell recordings. An inward rectifying potassium current
      (Ianom) typical for horizontal cells was activated in response to hyperpolarizing
      voltage steps. These types of currents have also been described in dissociated
      adult horizontal cells from lower vertebrates and cat. With single-channel
      recordings on inside-out patches excised from B-type cells, an additional Ca(2+)
      dependent current (IK(Ca)) was observed which, so far, has not been described in
      horizontal cells developing in situ. Our results demonstrate that cultured rabbit
      horizontal cells express a set of voltage-gated currents which largely, but not
      completely, corresponds to that described in situ for horizontal cells of other
      species. The culture system will allow further investigation of developmental and
      functional aspects of mammalian horizontal cells.

PMID- 7516182
TI  - Secondary structure and backbone dynamics of human granulocyte colony-stimulating
      factor in solution.
AB  - The secondary structure and backbone dynamics of the cytokine, human granulocyte
      colony-stimulating factor (hG-CSF) have been determined by heteronuclear nuclear
      magnetic resonance (NMR) techniques. Virtually complete NH, C alpha H, C beta H
      15N, 13C alpha, and 13C beta assignment of the 175-residue recombinant protein,
      methionyl-[Cys-17-Ser]-hG-CSF, was achieved by use of three-dimensional (3D)
      heteronuclear 1H-15N and triple-resonance 1H-15N-13C experiments. Spectra
      recorded at 750 MHz aided the assignment of severely overlapped regions. The
      structures of G-CSF from several species have recently been determined by X-ray
      diffraction [Hill, C. P., Osslund, T. D., & Eisenberg, D. (1993) Proc. Natl.
      Acad. Sci. U.S.A. 90, 5167-5171; Lovejoy, B., Cascio, D., & Eisenberg, D. (1993)
      J. Mol. Biol. 234, 640-653]. Like several cytokines, hG-CSF has a four-helix
      topology (A-D) with overhand loop connections, but with an additional helical
      segment (A') identified in the connection between helix A and helix B. The
      solution-state determination of the secondary structure is based on short- and
      medium-range NOEs, backbone J-couplings, and NH exchange data and is corroborated
      by 13C alpha secondary shifts. The helices are defined as follows: A, 10-38;
      A',44-53; B, 71-91; C, 102-123; D, 143-172. The dynamics of the amide backbone
      resonances, investigated using 1H-15N heteronuclear NMR, indicate a rigid protein
      core with some increased mobility in the AB loop and more pronounced mobility in
      the CD loop.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516181
TI  - Effects of minor groove binding drugs on the interaction of TATA box binding
      protein and TFIIA with DNA.
AB  - TBP (TATA box binding protein), a general transcription factor required for
      proper initiation of gene expression by RNA polymerase II, and minor groove
      binding drugs (MGBs) both interact with DNA within the minor groove at AT sites.
      This study has evaluated MGBs as inhibitors of DNA/TBP complex formation by gel
      mobility shift assays. Our results demonstrate that reversible MGBs (DAPI,
      distamycin A, Hoechst 33258, and netropsin) are effective inhibitors of the
      formation of DNA/TBP complex and that distamycin A is the most potent (0.16
      microM inhibits TBP complex formation by 50%). CC-1065, a drug that covalently
      binds to DNA in the minor groove, is even more active than distamycin A (0.00085
      microM inhibits TBP complex formation by 50%). Significantly more CC-1065 (0.009
      microM) is required to break up preformed DNA/TBP complex compared to the drug
      concentration needed to prevent complex formation. In comparison, the order of
      drug addition has little influence on the ability of reversible MGBs to disrupt
      DNA/TBP complex. In the presence of TFIIA, a factor that enhances TBP association
      with DNA, greater drug concentrations (distamycin A and CC-1065, respectively)
      are needed to disrupt a preformed complex of DNA/TBP/TFIIA. In comparison to
      MGBs, drugs capable of binding to DNA by intercalation are generally weaker at
      blocking TBP complex formation except for hedamycin, which can intercalate and
      irreversibly bind to DNA and is as effective as reversible MGBs.

PMID- 7516180
TI  - The retinal targets of centrifugal neurons and the retinal neurons projecting to
      the accessory optic system.
AB  - In birds, neurons of the isthmo-optic nucleus (ION), as well as "ectopic"
      neurons, send axons to the retina, where they synapse on cells in the inner
      nuclear layer (INL). Previous work has shown that centrifugal axons can be
      divided into two anatomically distinct types depending on their model of
      termination: either "convergent" or "divergent" (Ramon y Cajal, 1889; Maturana &
      Frenk, 1965). We show that cytochrome-oxidase histochemistry specifically labels
      "convergent" centrifugal axons and target neurons which appear to be amacrine
      cells, as well as three "types" of ganglion cells: two types found in the INL
      (displaced ganglion cells) and one in the ganglion cell layer. Labeled target
      amacrine cells have distinct darkly labeled "nests" of boutons enveloping the
      somas, are associated with labeled centrifugal fibers, and are confined to
      central retina. Lesions of the isthmo-optic tract abolish the cytochrome-oxidase
      labeling in the centrifugal axons and in the target amacrine cells but not in the
      ganglion cells. Cytochrome-oxidase-labeled ganglion cells in the INL are large;
      one type is oval and similar to the classical displaced ganglion cells of Dogiel,
      which have been reported to receive centrifugal input; the other type is rounder.
      Rhodamine beads injected into the accessory optic system results in retrograde
      label in both types of cells, showing that two distinct types of displaced
      ganglion cells project to the accessory optic system in chickens. The ganglion
      cells in the ganglion cell layer that label for cytochrome oxidase also project
      to the accessory optic system. These have proximal dendrites that ramify in the
      outer inner plexiform layer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516183
TI  - Interaction of nucleotides with acidic fibroblast growth factor (FGF-1).
AB  - A wide variety of nucleotides are shown to bind to acidic fibroblast growth
      factor (aFGF) as demonstrated by their ability to (1) inhibit the heat-induced
      aggregation of the protein, (2) enhance the thermal stability of aFGF as
      monitored by both intrinsic fluorescence and CD, (3) interact with fluorescent
      nucleotides and displace a bound polysulfated naphthylurea compound, suramin, (4)
      reduce the size of heparin-aFGF complexes, and (5) protect a reactive aFGF thiol
      group. The binding of mononucleotides, diadenosine compounds (ApnA), and
      inorganic polyphosphates to aFGF is enhanced as the degree of phosphorylation of
      these anions is increased with the presence of the base reducing the apparent
      binding affinity. The nature of the base appears to have much less effect.
      Photoactivatable nucleotides (8N3-ATP, 2N3-ATP, 8N3-GTP, and 8N3-Ap4A) were
      employed to covalently label the aFGF nucleotide binding site. In general, Kd's
      in the low micromolar range are observed. Protection against 90% displacement is
      observed at several hundred micromolar nucleotide concentration. Using 8N3-ATP as
      a prototypic reagent, photolabeled aFGF was proteolyzed with trypsin and
      chymotrypsin and labeled peptides were isolated and sequenced resulting in the
      identification of 10 possible labeled amino acids (Y8, G20, H21, T61, K112, K113,
      S116, R119, R122, H124). On the basis of the crystal structure of bovine aFGF,
      eight of the prospective labeled sites appear to be dispersed around the
      perimeter of the growth factor's presumptive polyanion binding site. On residue
      (T61) is more distally located but still proximate to several positively charged
      residues, and another (Y8) is not locatable in crystal structures. Using heparin
      affinity chromatography, at least three distinct photolabeled aFGF species were
      resolved. These labeled complexes display diminished affinity for heparin and a
      reduced ability to stimulate mitogenesis even in the presence of polyanions such
      as heparin. In conclusion, nucleotides bind apparently nonspecifically to the
      polyanion binding site of aFGF but nevertheless are capable of modulating the
      protein's activity. Evidence for the presence of a second or more extended
      polyanion binding site and the potential biological significance of these results
      in terms of potential natural ligands of aFGF are also discussed but not
      resolved.

PMID- 7516184
TI  - TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex
      with the serum protein inter-alpha-inhibitor.
AB  - TSG-6 is a secreted 35-kDa glycoprotein, inducible by TNF and IL-1. The N
      terminal portion of TSG-6 shows sequence homology to members of the cartilage
      link protein family of hyaluronan binding proteins. The C-terminal half of TSG-6
      contains a so-called CUB domain, characteristic for developmentally regulated
      proteins. High levels of TSG-6 protein are found in the synovial fluid of
      patients with rheumatoid arthritis and some other arthritic diseases. Here we
      show that TSG-6 readily formed a complex with a protein present in human, bovine,
      rabbit, and mouse serum. This complex was stable during SDS-PAGE under reducing
      conditions, and in the presence of 8 M urea. The protein that binds TSG-6 was
      purified from human serum and identified as inter-alpha-inhibitor (I alpha I) by
      N-terminal microsequencing. Microsequencing of the complex itself revealed the
      presence of TSG-6 and two of the three polypeptide chains of I alpha I (bikunin
      and HC2). Experiments with recombinant TSG-6 and I alpha I purified from human
      serum showed that the TSG-6/I alpha I complex is rapidly formed even in the
      apparent absence of other proteins at 37 degrees C, but not at 4 degrees C. The
      TSG-6/I alpha I complex was cleaved by chondroitin sulfate ABC lyase, suggesting
      that cross-linking by chondroitin sulfate is required for the stability of the
      complex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516185
TI  - The role of protein kinase A and protein kinase C in prostanoid IP receptor
      desensitization in NG108-15 cells.
AB  - Pretreatment of NG108-15 cells for 1 h with 1 microM phorbol 12-myristate,13
      acetate produced no significant effect on the subsequent stimulation of adenylate
      cyclase activity by the IP receptor agonist, iloprost, the adenosine A2 receptor
      agonist, N-ethylcarboxamidoadenosine (NECA), or sodium fluoride, suggesting that
      protein kinase C activation does not produce desensitization in this system.
      Pretreatment of cells with 10 microM iloprost or forskolin for 17 h produced a
      decrease in the specific binding of [3H]iloprost, consistent with a decrease in
      IP receptor number. Iloprost pretreatment produced a decrease in responses to
      iloprost, NECA and sodium fluoride, whereas forskolin pretreatment produced a
      decrease in subsequent responsiveness to iloprost and NECA, but the response to
      sodium fluoride remained unaffected. The desensitization produced by forskolin
      could be completely inhibited by the inhibitor of protein kinase A and protein
      kinase C, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), but H7 had no
      effect on the desensitization produced by iloprost.

PMID- 7516186
TI  - The mechanism of stimulation of brain phospholipase C-alpha by myelin basic
      protein involves specific interactions.
AB  - The modulation of a brain phosphoinositide-specific phospholipase C-alpha
      activity was studied using a variety of compounds of different charge. Detergents
      such as sodium deoxycholate and cetyltrimethylammonium bromide stimulated the
      phospholipase C activity when used alone but when used together the effects were
      not additive. Spermine was an effective inhibitor of the enzyme activity while
      the cationic peptide, Melittin, had no effect. The inositol phosphates produced
      by hydrolysis with phosphoinositide-specific phospholipase C were inhibitory
      while diacylglycerol and inositol did not affect the phospholipase activity.
      Myelin basic protein, which was previously shown to stimulate phospholipase C
      activity by 2.5-fold, did not interact with the anionic inositol phosphatases to
      any significant extent. Thus we concluded that the mechanism of stimulation was
      not due to relief of product inhibition. Crosslinking studies with the
      photoactivatable reagent, N-hydroxysuccinimidyl-4-azidosalicylic acid, showed
      that peptide 24-33 of myelin basic protein, which stimulated the activity almost
      as much as the native protein, interacted specifically with the phospholipase C.
      Thus the mechanism by which myelin basic protein stimulated the enzyme appeared
      to be through specific protein-protein interaction.

PMID- 7516187
TI  - Fourier transform infrared spectra studies of protein in reverse micelles: effect
      of AOT/isooctane on the secondary structure of alpha-chymotrypsin.
AB  - The amide I region Fourier transform infrared (FTIR) spectra of alpha
      chymotrypsin have been studied in deuterium oxide (D2O) solution and also in
      reverse micellar solution of AOT/isooctane. The Fourier second derivative was
      applied to all spectra, revealing that the amide I band of alpha-chymotrypsin in
      D2O and in reverse micellar solution consists of nine components. The band
      frequencies are assigned to alpha-helix, beta-sheet, random and turn structure.
      The second derivative spectra of alpha-chymotrypsin have been shifted in the
      reverse micellar solution of AOT/isooctane in comparison with its spectra in D2O.
      This shift has also changed the intensity of each band. Through accurate
      measurement of the band intensities, the relative amount of different structure
      of alpha-chymotrypsin can be estimated. The comparison of the calculated results
      obtained in D2O with those obtained in reverse micellar solution provides the
      possibility to analyze the effect of reverse micellar solution of AOT/isooctane
      on the secondary structure of alpha-chymotrypsin. The results indicate that the
      reverse micellar solution has decreased the amount of alpha-helix and beta-sheet
      structure and increased the amount of random and turn structure in alpha
      chymotrypsin. The increase of the amount of random structure might loosen the
      structure of alpha-chymotrypsin and change the activity of the enzyme.

PMID- 7516188
TI  - Effects on monoamine levels in rat CNS after chronic administration of cocaine.
AB  - We have previously reported time-dependent and dose-dependent changes in the rat
      dopaminergic receptor system following chronic administration of cocaine
      (upregulation of cocaine, D1, and DA-uptake sites). We have now evaluated the
      effects of chronic cocaine exposure on the central catecholamine/indolamine
      neurotransmitter systems. Groups of rats were injected with cocaine (15 mg/kg,
      i.p., b.i.d.) or saline for 1, 3, 7, 14 or 21 days. Cortical and striatal tissues
      were analyzed for norepinephrine, dopamine, serotonin and their primary
      metabolites using a HPLC-ECD method. Chronic administration of cocaine did not
      change the cortical and striatal concentrations of the neurotransmitters under
      study; except, for a transient increase in the cortical MHPG concentration on day
      3. These results suggest that changes in the dopaminergic receptor system
      following chronic cocaine exposure are not due to changes in the neurotransmitter
      concentrations.

PMID- 7516189
TI  - Isolation and identification of a FK-506 C36-C37 dihydrodiol from erythromycin
      induced rabbit liver microsomes.

PMID- 7516190
TI  - Failure of combination therapy with recombinant granulocyte colony-stimulating
      factor and erythropoietin in myelodysplastic syndromes.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) and
      erythropoietin (rhE-PO) were used to treat ten patients with myelodysplastic
      syndromes (MDS). None of the patients showed a favorable response in erythrocyte
      and platelet counts following 10 weeks' treatment, although favorable responses
      in neutrophil counts were observed in eight of ten patients (80.0%) and in seven
      of eight patients (87.5%) following 2 weeks' and 10 weeks' treatment,
      respectively. However, one patient with refractory anemia had a delayed favorable
      response in erythrocyte and neutrophil counts at week 14 in spite of the
      cessation of combination therapy at week 10. These results indicate that
      combination therapy with rhG-CSF and rhEPO is not beneficial to patients with
      MDS, based on the presently used protocol.

PMID- 7516193
TI  - Biological half-life of prostate-specific antigen after radical prostatectomy.
AB  - The disappearance pattern of prostate-specific antigen from serum after a
      standard radical prostatectomy was studied in eight patients with cancer confined
      to the prostate. The results were used to plot an elimination curve and calculate
      the best fit. A biphasic pattern was found with an average biological half-life
      of 1.63 hours in the alpha-phase, and 4.63 days in the beta-phase. Based on these
      results it is concluded that determination of prostate-specific antigen
      concentrations less than one month after a standard radical prostato
      vesiculectomy has no value for the detection or exclusion of residual malignant
      processes.

PMID- 7516194
TI  - Evaluation of an immunoradiometric assay for bone alkaline phosphatase mass
      concentration in human sera.
AB  - The performance characteristics of an immunoradiometric assay for bone alkaline
      phosphatase mass concentration in human sera are reported. Within-run imprecision
      (n = 20) was 12.1% (mean = 7.8 micrograms/l) and 3.6% (mean = 22.8 micrograms/l),
      between-day imprecision (n = 8) was 10.1% (mean = 20.3 micrograms/l) and 2.8%
      (mean = 84.3 micrograms/l). There was a linear relationship between the
      concentrations of the standards employed and the counts per minute up to 120
      micrograms/l. The detection limit was 0.3 micrograms/l. In 102 apparently healthy
      persons (51 males and 51 females; range of age: 18-56 years) the following
      reference intervals were established: 3.8-21.3 micrograms/l (males) and 3.4-15.0
      micrograms/l (females). We compared the values obtained using the immunoassay
      with those obtained by precipitating of bone alkaline phosphatase with wheat-germ
      lectin (alkaline phosphatase activity concentration was determined at + 25
      degrees C by the optimized standard method according to the Recommendations of
      the German Society for Clinical Chemistry). For the reference individuals the
      relationship between the results of the two methods is given by the following
      regression equation: Bone alkaline phosphatase activity concentration [U/l] =
      14.81 + 3.28 x bone alkaline phosphatase mass concentration [micrograms/l] (r = +
      0.783). In 89 sera from 32 patients before and after renal transplantation (range
      of bone alkaline phosphatase mass concentration: 2-39 micrograms/l) comparison
      between the two methods yielded a linear correlation coefficient of r = +
      0.886.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516191
TI  - Cell cycle kinetics of hematopoiesis before and after in vivo administration of
      GM-CSF in refractory anemia: evidence for a shortening of the granulocyte release
      time.
AB  - GM-CSF administration to patients with refractory anemia (RA) induces an increase
      in neutrophils and eosinophils. We studied cell kinetic mechanisms underlying
      this observation using clonogenic assays and in vivo iododeoxyuridine labeling of
      bone marrow cells. Cell cycle kinetics were studied in three patients before and
      during GM-CSF administration (two daily subcutaneous injections of 54 or 108
      micrograms). No consistent effect on the relative number of bone marrow CFU-GM
      was noticed. The DNA synthesis time and potential doubling time of low-density
      bone marrow cells remained essentially the same. A slight decrease (1.5-3.7%) in
      labeling index was found, originating from the myelo(-mono)cytic lineage. In all
      three patients the release time of labeled granulocytes from the bone marrow into
      the peripheral blood was shortened (before GM-CSF treatment 5-7 days and during
      GM-CSF 3-4 days). Cell cycle kinetics of CD34+ cells were studied in order to
      obtain kinetic information on immature precursor and progenitor cells. The DNA
      synthesis time of the CD34+ cells was shortened during GM-CSF therapy, resulting
      in a shorter potential doubling time. GM-CSF administration to patients with RA
      results in a rise in granulocytes that might be due partly to an accelerated
      release of granulocytes from the bone marrow compartment into the circulating
      blood and partly to an increased proliferative activity of the immature precursor
      and progenitor cells.

PMID- 7516192
TI  - The association between enteric bacterial overgrowth and gastrointestinal
      motility after subtotal liver resection or portal vein obstruction in rats.
AB  - OBJECTIVE: To test the hypothesis that intestinal motility is delayed after
      hepatectomy, which alters the ecology of the enteric microflora and contributes
      to the development of bacterial translocation from the gut. DESIGN: Open
      experimental study. SETTING: University department of surgery. MATERIAL: Adult
      male Sprague-Dawley rats (n = 6 in each group at each time point). INTERVENTIONS:
      Sham operation, 90% hepatectomy, and portal venous obstruction. MAIN OUTCOME
      MEASURES: Intestinal morphology, immunocytochemistry of the enteric nervous
      system, enteric bacterial growth in the small intestine and colon, and intestinal
      transit time. RESULTS: Intestinal transit was already delayed one hour after 90%
      hepatectomy, and histopathological alterations and overgrowth by Escherichia Coli
      had developed after two hours. There were significant differences in intestinal
      transit time between sham operated rats and those subjected to portal venous
      obstruction on the one hand, and those that underwent 90% hepatectomy on the
      other. There was no difference in intestinal transit time between rats with
      portal venous obstruction and the sham operated animals. CONCLUSION: Delayed
      intestinal transit after 90% hepatectomy may contribute to enteric bacterial
      overgrowth and thereby contribute to the development of bacterial translocation
      from the gut.

PMID- 7516195
TI  - Genotypes of hepatitis C virus in Guangxi province, southern China.
AB  - Hepatitis C virus (HCV) has been subdivided into at least four genotypes, and the
      prevalence of each genotype has been reported to differ widely in different
      countries. Of 304 patients with chronic liver diseases (68 with chronic
      hepatitis, 50 with liver cirrhosis and 186 with hepatocellular carcinoma) from
      Guangxi Province in southern China, only 9 (3.0%) had antibodies to HCV as
      determined by a second-generation enzyme immunoassay with a cut-off index of 2.0
      or more. The HCV genotypes of these nine cases were examined using polymerase
      chain reaction with type-specific primers deduced from putative core gene. Seven
      of the nine cases had type II infection and the other two cases showed double
      infection with types II and IV. These findings indicate that the predominant HCV
      genotype in the Guangxi area is type II, as is the case in Japan, although the
      prevalence of HCV infection in patients with chronic liver diseases is much
      lower.

PMID- 7516196
TI  - Nitric oxide modulates endogenous dopamine release in bovine retina.
AB  - A study of the possible modulation by nitric oxide (NO) of endogenous dopamine
      (DA) release was performed in bovine retina in vitro. NO synthase activity was
      measured in retinal homogenates and totally blocked by L-nitroarginine methyl
      ester (L-NA). Intact retinas were also exposed to hydroxylamine, an NO-generator
      which significantly decreased both basal and potassium-induced liberation of DA.
      In contrast, dibutyryl cGMP was ineffective. Furthermore, L-NA was able to
      increase basal DA release, its effects being potentiated in calcium free medium.
      Taken together, these results suggest that endogenous NO regulates DA release via
      cGMP independent mechanisms.

PMID- 7516198
TI  - Enkephalins occur and colocalize with substance P in human trigeminal ganglion
      neurones.
AB  - Immunohistochemical evidence is provided for (i) the occurrence of a primary
      sensory neuronal population immunoreactive to methionine- and leucine-enkephalin
      (EK) in the human trigeminal ganglion; (ii) colocalization of EK and substance P
      (SP) in a subpopulation of ganglion neurones and in nerve fibres and terminal
      like structures in the human trigeminal spinal nucleus. The results obtained
      indicate that part of the EK-positive innervation of the spinal nucleus may be of
      ganglionic origin and raise the possibility that EK and SP are co-stored in and
      co-released from primary afferent terminals, thus adding to the complexity of the
      sites and ways of interaction between these neuropeptides in the processing of
      sensory information.

PMID- 7516197
TI  - beta-Amyloid related peptides exert differential effects on [3H]MK-801 binding to
      rat cortical membranes.
AB  - The effects of beta-amyloid protein 1-40 (beta AP 1-40), substance P (SP), and
      the amidated and carboxylic acid C-terminated forms of the SP homologous beta AP
      fragment 25-35 (beta AP 25-35-NH2 and beta AP 25-35-COOH) were studied on [3H]MK
      801 binding to the rat brain NMDA receptor cation channel. All peptides gave dose
      dependent enhancements of [3H]MK-801 binding stimulated by low glycine. beta AP
      25-35-COOH, but not beta AP 25-35-NH2 produced an inhibition of [3H]MK-801
      binding stimulated by high glycine in the presence of either low or high
      glutamate. Low glutamate-stimulated [3H]MK-801 binding was also inhibited by SP
      but not by beta AP 1-40. It is concluded that beta AP related peptides exert
      differential effects on the NMDA receptor complex at the glycine and possibly
      also the glutamate recognition sites.

PMID- 7516200
TI  - Neuroendocrine regulation of growth hormone secretion in sheep. VI.
      Intracerebroventricular administration of galanin.
AB  - The effects of intracerebroventricular (i.c.v.) administration of galanin on
      plasma growth hormone (GH) concentrations and its possible mechanism of action
      have been examined in sheep. Galanin administration icv resulted in a dose
      dependent increase in plasma GH concentrations (p < 0.01). Concurrent
      administration of somatostatin (0.5 microgram kg-1 i.v. over 30 min) caused a
      delay in the GH response to galanin, but did not inhibit the GH release. These
      data show that galanin can stimulate GH release in sheep, but the mechanism
      through which this effect is mediated remains unclear.

PMID- 7516199
TI  - Nitric oxide synthase immunoreactivity in the rat dura mater.
AB  - The dura mater has been implicated as a tissue where vascular headache develops.
      Identification of the neural components of this tissue is a prerequisite for
      understanding the mechanisms of this pathological process. The nitric oxide
      molecule, a potent vasodilator, may contribute to the vascular headache process
      by dilating dural vasculature. Our immunohistochemical study using nitric oxide
      synthase (NOS) antibodies revealed NOS-positive nerve fibers and a prominent mast
      cell population in the rat dura. A majority of the immunopositive fibers were
      associated with the anterior meningeal artery and its branches and sparse
      innervation with the middle meningeal artery, its branches, and superior sagittal
      sinus. We propose that the NOS-positive nerve fibers and mast cells be considered
      as possible participants in the pathogenesis of vascular headache.

PMID- 7516202
TI  - A practical approach to hyperamylasemia.

PMID- 7516203
TI  - Pancreatic cancer in 1994: diagnosis and treatment.

PMID- 7516201
TI  - Triticum aestivum puroindolines, two basic cystine-rich seed proteins: cDNA
      sequence analysis and developmental gene expression.
AB  - From a mid-maturation seed cDNA library we have isolated cDNA clones encoding two
      Triticum aestivum puroindolines. Puroindoline-a and puroindoline-b, which are 55%
      similar, are basic, cystine-rich and tryptophan-rich proteins. Puroindolines are
      synthesized as preproproteins which include N- and C-terminal propeptides which
      could be involved in their vacuolar localization. The mature proteins have a
      molecular mass of 13 kDa and a calculated isoelectric point greater than 10. A
      notable feature of the primary structure of puroindolines is the presence of a
      tryptophan-rich domain which also contains basic residues. A similar tryptophan
      rich domain was found within an oat seed protein and a mammalian antimicrobial
      peptide. The ten cysteine residues of puroindolines are organized in a cysteine
      skeleton which shows similarity to the cysteine skeleton of other wheat seed
      cystine-rich proteins. Northern blot analysis showed that puroindoline genes are
      specifically expressed in T. aestivum developing seeds. No puroindoline
      transcripts as well as no related genes were detected in Triticum durum. The
      identity of puroindolines to wheat starch-granule associated proteins is
      discussed as well as the potential role of puroindolines in the plant defence
      mechanism.

PMID- 7516204
TI  - The pancreas.

PMID- 7516205
TI  - Abnormalities of blood coagulation and fibrinolysis in psoriasis.
AB  - Contrasting data have been reported about cardiovascular diseases in psoriatic
      patients. The aim of this study was therefore to evaluate blood coagulation and
      fibrinolysis in psoriatic patients. For this purpose, in a first group of 48
      patients, we measured blood coagulation and fibrinolysis inhibitors [antithrombin
      III (AT), protein C (PC) and alpha 2-antiplasmin (AP)], the products of thrombin
      and plasmin activity [fibrinopeptide A (FpA) and B beta(15-42) (B beta)],
      plasminogen (PLG) and fibrinogen (FBG). When all patients were considered we
      found a significant increase in B beta and FpA levels, while PC, PLG and AP
      values were significantly decreased when compared to controls. FBG and AT were
      not different from the controls. In order to understand whether the observed
      abnormalities of blood coagulation and fibrinolysis were related only to
      psoriasis we divided all the patients into two groups: (1) patients with
      cardiovascular disease or other risk factors (n = 28) and (2) patients affected
      only by psoriasis (n = 20). Since no difference was observed between groups 1 and
      2, we conclude that these findings are related to psoriasis. Subsequently we
      considered a different group of psoriatic patients. In these patients we measured
      FpA and two new thrombin activation indicators, such as prothrombin fragment 1 +
      2 and thrombin-antithrombin complex (TAT). In addition we evaluated the levels of
      D-dimer, the product of the dissolution of cross-linking fibrin by plasmin. In
      this second group FpA, prothrombin fragment 1 + 2 and D-dimer were significantly
      higher than controls. Only TAT was not statistically different from those of the
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516206
TI  - Mucopolysaccharide histochemistry of the oviduct of the toad, Bufo melanostictus,
      before and during ovulation.
AB  - In both non-ovulating and ovulating toads of the species, Bufo melanostictus, the
      fimbrium stained only weakly for mucopolysaccharides (MPs) whereas the
      infundibulum stained strongly for neutral MPs and also for glycogen. In the non
      ovulating toad, only neutral and sulphated MPs were detected in the goblet cells
      of the upper magnum, whereas sulphated, neutral and sialomucins were detected in
      the glands. In the middle magnum, sulphated and sialic acid-containing
      carboxylated MPs were detected in both the goblet cells and glands. In the lower
      magnum, neutral, sulphated, and sialic acid-containing MPs were detected in the
      goblet cells and only sulphated and sialic acid-containing MPs were detected in
      the glands. In the isthmus and ovisac, only sulphated MPs were present in the
      goblet cells. During ovulation, there was no change in the distribution of
      sulphated MPs throughout the oviduct. Sialic acid-containing MPs could not be
      detected in many of the goblet cells of the upper and lower magnum nor in most of
      the glands of the lower magnum.

PMID- 7516207
TI  - Peculiarities of the thyroid gland structure (with special reference to the
      presence of ganglion cells).
AB  - We have performed a study on the comparative structure of the thyroid gland in
      several species of mammals (rat, cat, dog, lamb, pig, cow, and man). We have
      described the structural differences among them, paying special attention to the
      distribution of connective tissue, the intrafollicular and parafollicular cells.
      In the thyroid gland, we can confirm the existence of nerve cells, either
      isolated or forming vegetative ganglions in the interfollicular spaces, in some
      of the species studied, especially in the rat and the dog.

PMID- 7516209
TI  - Experimental rat pancreas transplant: surgical technique and immunological
      considerations.
AB  - Vascularized whole pancreas transplantation in the rat was performed on the
      abdomen using a cuff technique for vascular anastomoses. Two different exocrine
      drainage procedures, either intestinal or ureter drainage, were used. In the
      isograft transplant models, hyperglycemia was ameliorated immediately after
      transplantation and all of the grafts functioned during the observation period.
      In the allograft transplant models without immunosuppression, graft rejection, as
      defined by recurrence of hyperglycemia (blood glucose > 200 mg/dl) occurred 6-9
      days post-transplant. Allograft rejection could be delayed approximately 1 month
      after transplant with short-term use of FK506. These different models, using
      either intestinal or ureter exocrine drainage, are similar to dominant clinical
      pancreas transplantation with enteric exocrine drainage or urinary tract
      drainage, respectively. It is thus concluded that whole pancreas transplant with
      either intestinal or ureter exocrine drainage is an ideal model for physiological
      and immunological experimental studies in pancreas transplantation.

PMID- 7516208
TI  - 5-HT1-receptor-mediated vasoconstriction in bovine isolated pulmonary arteries:
      influences of vascular endothelium and tone.
AB  - Vasoconstrictor responses to 5-hydroxytryptamine (5-HT) and the 5-HT1D receptor
      agonist sumatriptan were studied in isolated bovine pulmonary artery rings. The
      effects of the antagonists, ketanserin (5-HT2A-receptors) and methiothepin (5-HT1
      and 5-HT2A-receptors) on these responses were determined. The influences of
      vascular tone and the effect of removal of the vascular endothelium and
      pretreatment with the inhibitor of nitric oxide synthase, N omega-nitro-L
      arginine methylester, were also studied. In the absence of tone, in the majority
      of vessels, sumatriptan did not induce significant contractions. 5-HT-induced
      responses were concentration-dependent and ketanserin and methiothepin
      antagonized these in a competitive fashion. Removal of the endothelium or
      inclusion of L-NAME potentiated responses to sumatriptan. The sensitivity to
      sumatriptan was increased by L-NAME only in the presence of the endothelium
      whilst maximum responses to sumatriptan were potentiated in both unrubbed and
      rubbed vessels. Removal of the endothelium and/or inclusion of L-NAME had no
      significant effect on responses to 5-HT. U46619-induced tone markedly increased
      sumatriptan-induced responses which were competitively antagonized by
      methiothepin but were relatively resistant to ketanserin, verifying activation of
      a 5-HT1D receptor. Responses to 5-HT were also potentiated and competitively
      antagonized by ketanserin, and further antagonized by methiothepin. With tone
      present, lower concentrations of 5-HT were ketanserin-resistant and methiothepin
      sensitive, indicating activation of a 5-HT1-like receptor.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7516212
TI  - [Treatment of short esophageal stricture in children].
AB  - The authors find it necessary to identify a nosological entity of short
      esophageal strictures, up to 1.5-2.0 cm long, from the specific features of their
      formation, clinical manifestations and from the possibility of widely using
      transesophageal methods of treatment. Among them, a procedure for intraesophageal
      compression of the scarring ring by using two types of devices in 64 patients was
      analysed. There was a positive result in 86% of the patients. The remaining
      children underwent surgical interventions: resection of an esophageal portion
      with esophagus-esophagus anastomosis and colesophagoplasty. No deaths were
      recorded. To objectivize the indications for either method of treatment, the
      authors recommend esophageal NMR tomography.

PMID- 7516211
TI  - [Duodenal function in some diseases of upper abdominal organs].
AB  - Eighty-five children with surgical parasurgical and pediatric abnormalities of
      upper abdominal organs were studied. In addition to the routine procedures, the
      authors used the following: endoscopic stepwise manometry, electromyography,
      polarography, pH-metry. In some chronic pediatric diseases, manometric,
      polarographic, electromyographic changes were found to correlate with the similar
      ones in surgical abnormalities. The findings provide strong evidence for the
      necessity of more comprehensive examinations of the duodenum in children with
      surgical and pediatric upper abdominal abnormalities in order to earlier detect
      the indications for surgical treatment, to assess the outcomes of treatment and
      to predict the course of rehabilitation.

PMID- 7516210
TI  - Limited effectiveness of FK506 administration for ongoing rejection in
      heterotopic rat heart transplantation.
AB  - A comparison was made of the histological findings for myocardial tissue of
      heterotopic transplanted rat hearts administered with FK506. ACI rats were used
      as donors and Lewis rats as recipients. FK506 was used for 6 days except for
      group I (control group). Group II received 0.32 mg/kg/day of FK506 from the day
      of operation while group III was given the same dosage from the 4th day after
      transplantation. Group IV was given 1.28 mg/kg/day of the agent from the day of
      grafting and group V received the same dose from the 4th postoperative day. The
      graft survival time was longer for all groups given FK506, but was significantly
      longer only for groups administered with FK506 from the day of operation.
      Histological studies performed 10 and 20 days after transplantation showed that a
      moderate rejection was seen in about half of the grafts receiving FK506 from the
      4th day after grafting. An ultrastructural study of these cases showed that
      infiltrating large lymphocytes still remained in the interstitial tissues and
      that the cytoplasmic organelles of the myocytes had been focally destroyed. These
      results suggest that, although FK506 suppressed any further rejection, the effect
      might be limited and the myocardial changes of the cardiac graft might persist
      even after administration for ongoing rejection.

PMID- 7516213
TI  - [Improvement of methods of surgical correction of congenital hydronephrosis in
      children].
AB  - The analysis of the authors' own results of surgical treatment for hydrohephrosis
      in 81 children after the Anderson-Haines-Kucher has revealed that the most common
      complication is stenosis of the anastomosis made. The authors' modified operation
      has indicated that the use of a less traumatic access to the pelvioureteral
      portion, of optic magnification, a microsurgical instrument, 7/0 synthetic suture
      material, drainage of the renal collecting system with a pyelostomic tube of
      original design allows the optimal conditions to be created for formation of the
      pelvioureteral anastomosis and the good results of hydronephrosis treatment to be
      obtained in children.

PMID- 7516214
TI  - [Use of ultra high-frequency electromagnetic fields in pediatric surgery].
AB  - The procedures associated with the application of a super-frequency
      electromagnetic field (SFEMF) are being introduced into a therapeutical process
      in their various modifications at the Pediatric Surgery Hospital of Russian State
      Medical University. This has been preceded by enormous experimental work aimed at
      evaluating the potentialities of SFEMF for potentiation of cryogenic exposure and
      for individual use for endovascular occlusion and local hyperthermia. A total of
      947 patients were treated with SFEMF from 1979 to 1990. The largest group
      included children with hemangiomas of various site (n = 465) and those with
      cheloid scars (n = 395). Thirty-one patients underwent intravascular coagulation
      with SFEMF in the treatment of arterial and venous malformations and 31 patients
      were treated for pigmentary spots of various site with SFEMF + cryodestruction.
      Local hypothermia was performed in 25 children with extensive hemangiomas of the
      face and neck with SFEMF. The total therapeutical benefits reached 98%. For these
      purposes the authors used a Plot routine apparatus, 915 mHz, with a set of
      contact and special emitters. The experience with SFEMF in pediatric surgery
      suggests that it is highly effective and the trend is promising.

PMID- 7516215
TI  - [Objective evaluation of the pain syndrome and postoperative analgesia in
      children].

PMID- 7516216
TI  - [Free calipsol concentration - the most objective criterion of anesthesia
      intensity in children].

PMID- 7516217
TI  - [Syndrome-based approach to the problem solving in pediatric surgery: theoretic
      rationale, achievements and perspectives].

PMID- 7516218
TI  - [Use of the current cardiac inotropic agent dobutamine in pediatric surgical
      clinics].

PMID- 7516219
TI  - [Continuous epidural infusion of lidocaine in children for intra- and
      postoperative analgesia].

PMID- 7516220
TI  - [Non-contact, biologically adequate, electromagnetic stimulation of reparative
      regeneration of osseous, cartilagenous and muscular tissues in children].
AB  - The authors analyse the results of using a Kaskad electromagnetic apparatus in
      508 children with long-term ununited fractures, false joints, contractures,
      sluggish wounds, decubituses, trophical ulcers, osteochondropathies, Pertes'
      disease, and crush syndrome. The efficiency of the therapy was 75-90%, depending
      on the type of an abnormality. The authors had developed and put into practice a
      Kaskad-synchro electromagnetic apparatus synchronized with the pulse of a
      patient's arterial vessel. Such a high efficiency of the electromagnetic therapy
      bioadequate to man is likely to be explained by the exposure of electromagnetic
      waves directly to the areas of bone marrow hemopoiesis. To elucidate this, the
      authors made an experiment on dogs. The results of this experiment are being
      processed.

PMID- 7516221
TI  - [Study on translocation of intestinal microflora into the blood of mesenteric
      vessels and lymph nodes in children with portal hypertension syndrome].
AB  - A total of 42 children aged 6 months to 14 years who had the portal hypertension
      syndrome were studied. Blood and a lymph node were taken during a planned surgery
      by applying venous anastomosis. Translocation to the veins of the small and large
      bowels and to the mesenteric lymph nodes were recorded in 35 (83.3%), 34 (81%),
      and 17 (41%) patients, respectively. Translocation of aerobic bacteria (81, 78.6,
      and 40.5%) was more common than that of anaerobic ones (11.9, 11.9, and 4.8%) to
      the blood of the small and large bowels and lymph nodes, respectively, gram
      negative bacteria heading the list in their frequency, Streptococci ranking next
      to the latter. The data on the composition of fecal microflora in the same
      children prior to surgery are given in the paper, which suggests that they had
      compensatory dysbacteriosis. A contribution of various factors (portal
      hypertension, operative stress, dysbacteriosis, etc.) to the development of
      translocation and its pathogenetic value are discussed too.

PMID- 7516222
TI  - [Endovascular occlusion of the spleen in pediatric practice].
AB  - A procedure has been developed for partial X-ray endovascular occlusion of the
      spleen in children. Splenic occlusion has been performed in 74 patients with
      various blood diseases and portal hypertension for 4 years. Indications for
      partial "disconnecting" of the splenic parenchyma have been identified depending
      on a specific disease. Its low traumatism, prevention of septic complications by
      using selective intestinal flora decontamination and choosing antibiotics at an
      individual level allow splenic occlusion to be made in young children. In
      patients with portal hypertension, partial splenic occlusion leads to
      decompression in the portal vein system and improves blood ejection along the
      natural vascular anastomoses.

PMID- 7516223
TI  - [Ultravist - drug of choice for radioopaque studies in children with renal
      disfunction].
AB  - The nonionic radioopaque ultravist and the high-molar radioopaque verograffin
      were studied for their effects on the blood osmotic status of children with lower
      renal concentrating function. A total of 36 children aged 8 months to 12 years
      who had pyelonephritis, hydronephrosis and renal injury at their acute stage were
      studied angiographically under general anesthesia. The radioopaque was injected
      in a mean dose of 2 ml/kg for 2-3 sec. Ultravist was found to have a less osmotic
      action on the blood osmotic status than did verograffin. The changes in the
      detectable major blood osmotic parameters: sodium, potassium, glucose, urea,
      creatine were less pronounced. Plasma osmolality was moderately increased with
      ultravist and much higher than its normal values with verograffin at min 1 after
      its administration and at hour 2 of the study. Ultravist is preferable as a
      radiopaque used in children with decreased renal concentrating function.

PMID- 7516225
TI  - [Treatment of children with myelodysplasia, complicated by vesicoureteral
      reflux].
AB  - Timely detection of various neurogenic urinary bladder dysfunctions in children
      with congenital lesions of caudal regions of the spine and their treatment in due
      time enable the urinary dynamics of the lower urinary tract to be stabilized
      early. The efficient application of conservative treatments contributes to the
      recovery of detrusor performance and urethral and anal sphincters in some spinal
      patients; however, the maximum effect was achieved in patients who had undergone
      intercostal autoneuroplasty. Microneurosurgical interventions on the lumbosacral
      roots of the spine are most likely to produce a pelvic reinnervation effect to
      some extent and promotes the regression of vesicoureteral reflux.

PMID- 7516224
TI  - [Laser reflexotherapy in the combined treatment of neurogenic bladder dysfunction
      in children with caudal regression syndrome].
AB  - The authors propose to introduce low-energy laser reflexotherapy to the complex
      of rehabilitative therapy for children with neurogenic dysfunction of the urinary
      bladder. The laser causes no pain, which enables the procedure to be used in
      infants, eliminates unretarded contractions of a detrusor rather effectively. A
      continuous reproduction of this therapeutic complex can be achieved by a
      relatively long-term stabilization of urination in a third of the children.

PMID- 7516226
TI  - [Sacral proctoplasty in the treatment of anorectal malformations in children].
AB  - The paper describes novel procedures for sacroperineal, sacroabdominoperineal and
      posterosagittal proctoplasties during radical correction of various types of
      anorectal malformations and their sequelae in children of all age groups,
      including neonates. Some technical features of their performance are considered
      and the outcomes of treating 84 children are analyzed. The proposed scheme for
      surgical treatment allows one to achieve good and satisfactory late functional
      results in 80 per cent of patients with anorectal atresias and incontinence of
      feces.

PMID- 7516227
TI  - [Lactate dehydrogenase X - specific enzyme of the testis].

PMID- 7516228
TI  - [Kidney autotransplantation in children].
AB  - A total of 4 renal autotransplantations were performed in children in the
      hospital. The indications for the surgery were ureteric injury (n = 2) and
      megaloureter associated with distal ureteric stenosis (n = 2). In all cases,
      autotransplantation was conducted into the ipsilateral iliac fossa after
      perfusion cooling of the kidney for an average of 28 min. No postoperative
      complications were observed. There was a complete recovery of renal function in
      all cases.

PMID- 7516229
TI  - A SV-40 immortalized murine endothelial cell line from peripheral lymph node high
      endothelium expresses a new alpha-L-fucose binding protein.
AB  - Endothelial cells from mouse peripheral lymph nodes were immortalized by cationic
      liposome-mediated transfection using a plasmid construct containing both the gene
      coding for the large T antigen of simian virus 40 and a geneticin resistance gene
      suitable for selection. A cell line (HECa10) was isolated on the basis of its
      capacity to specifically bind fucoside carrying glycoconjugates; these cells
      present the main characteristics of endothelial cells: production of angiotensin
      converting enzyme and of factor VIII-related antigen. Upon stimulation, they
      express E-selectin which binds oligosaccharides containing the Lewisx determinant
      (Fuc alpha 3[Gal beta 4 GlcNAc beta 3Gal beta) and the MECA 79 addressin which is
      characteristic for the peripheral lymph node high endothelium and is a L-selectin
      ligand. HECa10 cells, as well as peripheral lymph node high endothelial cells in
      primary culture, express a second fucoside binding protein which differs from E
      selectin. Indeed, this new fucoside-binding protein is constitutively expressed
      on unstimulated cells while E-selectin is not. Furthermore, HECa10 cells mediate
      selective lymphoid cell adhesion in a selectin/addressin-dependent mechanism,
      mainly inhibited by MECA 79 antibody and, in a fucose-binding lectin-dependent
      manner, mainly inhibited by the specific neoglycoprotein.

PMID- 7516230
TI  - Leishmania donovani flagellum-specific epitopes mediating host-parasite
      interactions.
AB  - Monoclonal antibodies were developed against flagellar components of
      promastigotes of Leishmania donovani. The monoclonal antibody produced by clone
      A11 (mAb A11) recognised epitopes in the polypeptides with molecular weights of
      86, 66 and weakly 53 kDa. These epitopes were found to be distributed along the
      flagellum and at the anterior end of promastigotes. The mAb A11 of IgG1 isotype
      strongly agglutinated the promastigotes of L. donovani. The prior treatment of
      promastigotes of L. donovani with mAb A11 resulted in a significant (P < 0.001)
      reduction in the attachment of promastigotes to cultured mouse peritoneal
      macrophages of line J774G8. The affinity-purified epitopes identified by mAb A11
      were recognised by human sera of cases of visceral leishmaniasis. The present
      study suggest that flagellar-specific epitopes mediate host-parasite interactions
      and, therefore, the role of these epitopes in the disease process is speculated.

PMID- 7516234
TI  - Identification of a 6 bp deletion (3195del6) in exon 17a of the cystic fibrosis
      (CFTR) gene.

PMID- 7516231
TI  - Polymorphonuclear granulocyte expression of CD11a/CD18, CD11b/CD18 and L-selectin
      in normal individuals.
AB  - In this study direct immunofluorescence and flow cytometry with calibration using
      quantitative bead standards were used to enumerate the cell surface receptors
      CD11a/CD18, CD11b/CD18 and L-selectin. Holding blood at room temperature and
      fixation of samples prior to staining induced changes in expression, while
      immediate staining of polymorphonuclear granulocytes (PMN) in whole blood
      followed by fixation produced accurate values. The ranges of PMN adhesion
      molecule expression in 10 normal individuals were CD11a/CD18: 14794-28725,
      CD11b/CD18: 5300-11939 and L-selectin: 35662-61654 receptors per cell.
      Differences within individuals over 4 h were also observed. Adhesion molecule
      expression is used as an index of the adhesive function and state of activation
      of the cell. The data presented here shows that there is inherent variability in
      the expression of the PMN adhesion molecules between and within individuals, thus
      direct comparisons of PMN adhesion molecule expression between patients and
      "normals" must be interpreted with caution.

PMID- 7516233
TI  - A novel splice site mutation in the first exon of the cystic fibrosis
      transmembrane regulator (CFTR) gene identified in a CBAVD patient.

PMID- 7516232
TI  - A new missense mutation (G27E) in exon 2 of the CFTR gene in a mildly affected
      cystic fibrosis patient.

PMID- 7516235
TI  - 1462V mutation in the human CYP1A1 gene: lack of correlation with either the Msp
      I 1.9 kb (M2) allele or CYP1A1 inducibility in a three-generation family of east
      Mediterranean descent.
AB  - A 15-member three-generation family of Eastern Mediterranean descent was
      previously studied, and an association between CYP1A1 (cytochrome P1450,
      benzo[a]pyrene hydroxylase) inducibility and a CYP1A1 3'-polymorphism (the Msp I
      1.9 kb allele) was reported (Petersen et al., Am J Hum Genet 1991:48, 720-725).
      Here we have re-examined the original DNA (and in some cases, newly prepared DNA
      from freshly drawn blood) from these same individuals, in order to assess the
      association between CYP1A1 inducibility and both the CYP1A1 gene Msp I RFLP
      polymorphism and the CYP1A1 gene A-->G polymorphism at codon 462. This latter
      nucleotide change results in an altered amino acid (462Ile-->Val), which is
      purported to increase CYP1A1 enzyme activity and mutagenicity towards
      benzo[a]pyrene about two-fold among Japanese. Among the 15 members of this three
      generation family examined, no absolute correlation was observed between the
      1462V genotype and either the Msp I 1.9 kb allele or the CYP1A1 inducibility
      phenotype. We also found no absolute correlation between the Msp I 1.9 kb allele
      and the CYP1A1 inducibility phenotype.

PMID- 7516236
TI  - Salmonella javiana in Europe.

PMID- 7516237
TI  - Toxic shock syndrome and related conditions in the United Kingdom: 1992 and 1993.

PMID- 7516238
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7516239
TI  - Prediction of RNA secondary structure by energy minimization.

PMID- 7516240
TI  - Submission of nucleotide sequence data to EMBL/GenBank/DDBJ.

PMID- 7516241
TI  - Use of hydrophobic affinity partitioning as a method for studying various
      conformational states of the human alpha-macroglobulins.
AB  - The serum proteins alpha 2-macroglobulin and pregnancy zone protein undergo major
      conformational changes when complexed with proteinases. It is shown that the
      changes in delta log Kmax determined by hydrophobic affinity partitioning is a
      measure of the extent of changes in the conformation of these alpha
      macroglobulins. We introduce a new term for the changes of surface hydrophobicity
      in a protein as delta log Kacc. This defines the difference of delta log Kmax
      between a modified and an unmodified conformational state of a specific protein
      and can be useful as a parameter to describe the apparent conformational changes
      in the protein.

PMID- 7516242
TI  - Partitioning of chemically modified low-density lipoprotein in aqueous polymer
      two-phase systems.
AB  - Aqueous polyethylene glycol (PEG)-dextran two-phase systems containing 10 mM
      Tris.HCl (pH 7.4) were used for the partitioning of chemically modified low
      density lipoprotein (LDL). Anionic modification connected with an increase in the
      negative surface charge of lipoproteins favours the accumulation of modified LDL
      in the top phase. The partition coefficient increases depending on the extent of
      modification. Cationic modification yields lower values for the partition
      coefficient. Positively charged LDL favours a bottom-phase accumulation. With
      weakly charged and nearly neutral particles, the Van der Waals interaction
      between polymer and particle preponderates over electrostatic interactions,
      leading to a favoured accumulation of LDL in the PEG-rich top phase. Results of
      measurements of the relative electrophoretic mobility and the determination of
      free amino groups are in agreement with the calculated values of the partition
      coefficient. Because the partitioning of LDL is accompanied by aggregation at the
      interface, experimental techniques have to be carefully standardized. Subtle
      differences in the surface properties of modified LDL can be detected.

PMID- 7516243
TI  - Integration of aqueous two-phase extraction and affinity precipitation for the
      purification of lactate dehydrogenase.
AB  - Integration of extraction in aqueous two-phase system and affinity precipitation
      was investigated as a technique for purification of lactate dehydrogenase (LDH)
      from porcine muscle extract. An enteric coating polymer, Eudragit S 100, which
      can be made reversibly soluble and insoluble by change in pH was used as the
      ligand carrier. The ligand used was Cibacron blue 3GA. The polymer is nearly
      totally partitioned to the top phase (> 98%) in PEG-dextran aqueous two-phase
      system. The enzyme, lactate dehydrogenase, was first spontaneously partitioned to
      the bottom phase in a 6% (w/w) PEG 8000-8% (w/w) dextran T250 phase system. New
      PEG phase and Eudragit-dye were then added to the bottom phase, which helped in
      extraction of LDH to the top phase. After a washing step with a fresh bottom
      phase, Eudragit-dye-target protein affinity complex was precipitated out from the
      top phase by lowering the pH to 5.1. The enzyme was recovered by treatment of the
      complex with 0.5 M NaCl with a yield of 54% and a specific activity of 245
      units/mg. The purification of LDH by this procedure was better than that obtained
      by a single step of affinity partitioning.

PMID- 7516244
TI  - Revealing surface changes associated with maturation of ram spermatozoa by
      centrifugal counter-current distribution in an aqueous two-phase system.
AB  - Centrifugal counter-current distribution (CCCD) in an aqueous two-phase system
      was used to detect changes associated with maturation of ejaculated ram
      spermatozoa. Spermatozoa obtained from three successive ejaculates of rams
      maintained in abstinence for one, two and three days were fractionated by CCCD.
      The results show that these ejaculates are relatively enriched in a cell
      population which presents a very high enhanced affinity to the lower dextran-rich
      phase. This cell population is not associated with loss of acrosomal integrity.
      In addition, it tends to disappear with longer abstinence periods, or after
      successive ejaculations at the same abstinence period, strongly suggesting that
      it is composed of immature cells. Therefore, phase partitioning can detect
      surface changes accompanying sperm maturation and offers a new possibility for
      sperm quality analysis.

PMID- 7516245
TI  - Cell partitioning in two-polymer aqueous phase systems and cell electrophoresis
      in aqueous polymer solutions. Red blood cells from different species.
AB  - A correlation, with some exceptions, between the partitioning behavior of red
      blood cells (RBCs) from different species in charge-sensitive dextran
      poly(ethylene glycol) (PEG) aqueous phase systems and their relative
      electrophoretic mobilities (EPMs) in phosphate-buffered saline (PBS) has
      previously been reported. This relationship has now been further probed by
      carrying out RBC electrophoresis in media (i.e., dextran-rich bottom or PEG-rich
      top phases) more closely approximating the environment in which RBC partitioning
      takes place to see whether a better correlation would ensue. The ratios of
      viscosity-corrected EPMs of different species' RBCs in (diluted) dextran-rich or
      PEG-rich phases/EPMs of the respective species' RBCs in PBS differ for a number
      of species, and from each other, reflecting thereby differences in kind (i.e.,
      dextran or PEG) and nature of polymer interaction with these RBCs. There is a
      general tendency for EPMs in any of the tested media to correlate with both the
      cells' relative partition ratios as well as with their relative EPMs in one of
      the other media. However, examination of the behavior of different species' RBCs
      taken two species at a time indicates that their relative EPMs in any two
      suspending media or in one suspending medium and partitioning often differ. Thus,
      both the cell partition ratio and the cell EPMs obtained in polymer media must,
      at least in some cases, reflect surface properties other than or in addition to
      the charge reflected by EPM measurements in PBS or saline. Cell electrophoresis
      in polymer solutions thereby provides an additional parameter for discriminating
      between surface properties of certain closely related cell populations.

PMID- 7516246
TI  - Experimental basis for separation of membrane vesicles by preparative free-flow
      electrophoresis.
AB  - In practice it has been possible to separate membrane particles of different
      origins but of similar chemical composition by preparative free-flow
      electrophoresis. Examples include the vacuolar (tonoplast) and plasma membranes
      of plants and membranes derived from the cis and trans regions of the rat liver
      Golgi apparatus. Yet, when analyzed for intrinsic molecules that might contribute
      to significant differences in surface charge, the separated membranes were
      surprisingly similar. As more information was generated, it became apparent that
      the membranes with greatest electrophoretic mobility (i.e. lysosomes, rightside
      out tonoplast vesicles and membranes from the trans region of the Golgi
      apparatus), where those membranes with an inherent ability to acidify their
      interiors. By so doing, the vesicles generate a membrane potential, negative
      outside, which might serve as a basis for enhanced electrophoretic mobility. To
      test the hypothesis, tonoplast membranes were incubated with ATP to drive proton
      import or with monensin to dissipate the ATP-supported proton gradient. With ATP,
      mobility was enhanced. Also, when ATP-treated vesicles were analyzed in the
      presence of monensin, the ATP effect on mobility was reversed. Similarly with
      Golgi apparatus, mobility of the most electrophoretically mobile portions of the
      separation was enhanced by ATP and the ATP effect was reversed with monensin. A
      trans origin of the vesicles was verified by assay of the trans Golgi apparatus
      marker, thiamine pyrophosphatase. Finally, incubation with ATP (and reversal by
      monensin) was employed as an aid to the free-flow electrophoretic separation of
      kidney endosomes from complex mixtures. These lysosomal derivatives also are
      capable of acidification of their interiors in an ATP-dependent process and of
      generating, at the same time, a negative (outside) membrane potential. The
      findings provide both an experimental basis to enhance membrane separations by
      preparative free-flow electrophoresis and, at the same time, a theoretical basis
      to help explain why certain membranes of very similar overall chemical
      composition may be separated by electrophoretic methods.

PMID- 7516247
TI  - Interactions between fluoroquinolones, Mg2+, DNA and DNA gyrase, studied by phase
      partitioning in an aqueous two-phase system and by affinity chromatography.
AB  - The primary target of fluoroquinolones has been identified as the enzyme DNA
      gyrase, but the mechanism of action of these antibacterial agents is still a
      matter of controversy. Using partitioning in aqueous polyethylene glycol (PEG)
      dextran systems, the affinities of several fluoroquinolones for DNA were
      determined with accuracy and at equilibrium. It was proved that the binding was
      strongly dependent on the ability of the drugs to bind Mg2+, with KA values of
      about 40 000 l mol-1, but was poorly related to the antibacterial activity
      [minimal inhibitory concentration (MIC) and gyrase inhibition]. Using affinity
      chromatography on immobilized fluoroquinolone, it was shown that DNA gyrase was
      unable to bind fluoroquinolones in the absence of DNA, but that a DNA-quinolone
      gyrase complex was formed in the presence of Mg2+.

PMID- 7516248
TI  - Improved method for preparation of lipopolysaccharide-binding protein from human
      serum by electrophoretic and chromatographic separation techniques.
AB  - Recent work has established the importance of serum proteins which interact with
      endotoxin (lipopolysaccharide, LPS) from Gram-negative bacteria. Thus human
      monocytes are activated after binding LPS complexed with a serum protein. LPS
      binding protein (LBP) is a protein present in both normal and acute phase sera
      which binds LPS with high affinity. We describe the purification of LBP from
      human acute phase serum. The purification procedures combine preparative
      isoelectric focusing (IEF) and either preparative polyacrylamide gel
      electrophoresis (PAGE) or alternatively an anion-exchange chromatographic step
      using a Mono Q HR 5/5 column. This allows the isolation of biologically active
      LBP. LBP was characterized by N-terminal sequence analysis and by measuring the
      biological activity using flow cytometry (fluorescence-activated cell sorter,
      FACS) and a luminol enhanced chemiluminescence (LECL) assay.

PMID- 7516249
TI  - Reflection confocal imaging of type I and type III isozymes of hexokinase in PC12
      cells.
AB  - Reflection confocal microscopy was used to determine the intracellular
      distribution of Type I and III isozymes of hexokinase (ATP:D-hexose 6
      phosphotransferase, EC 2.7.1.1) in PC12 cells; detection was by staining with
      diaminobenzidine as a substrate for horseradish peroxidase-conjugated antimouse
      immunoglobulins bound to isozyme-specific monoclonal antibodies. With both
      isozymes, detection of the staining pattern was significantly enhanced by
      reflection confocal imaging compared with viewing with transmitted brightfield
      optics. For Type I, prominent staining of cytoplasmic organelles having a
      distribution consistent with that of mitochondria was noted. For Type III,
      intense staining at the nuclear periphery was observed. A distinct punctate
      pattern along the nuclear surface implied a nonuniform distribution of the Type
      III hexokinase and may represent preferential association with nuclear pore
      structures. A study of technical factors involved in optimizing the reflection
      image was conducted. We demonstrate that both the choice of objective and the
      thickness of the mounting medium are critical to successful imaging, and we
      describe a simple test for assessing the suitability of objectives in any system.

PMID- 7516251
TI  - Infectious complications of lung transplantation. Impact of cystic fibrosis.
AB  - It has been suggested that the presence of airway pathogens prior to lung
      transplantation (LT) in patients with cystic fibrosis (CF) may place these
      patients at a higher risk for infectious complications after LT. There is
      particular concern regarding patients colonized with multiresistant Pseudomonas,
      including P. cepacia, and fungi, including Aspergillus. We report our experience
      with LT for patients with CF and compare the results with those of patients with
      LT for other indications. Between January 1990 and March 1993, we performed LT
      for 27 patients with CF and 32 without CF. Nearly all (89%) of the patients with
      CF were colonized with P. aeruginosa; many were cultured with P. cepacia (19%)
      and Aspergillus (63%). The non-CF group rarely had organisms identified pre-LT.
      No patients with CF underwent pre-LT sinus drainage or received pre-LT treatment
      for Aspergillus. All of the patients received perioperative antibiotics and a
      standard regimen of immunosuppression and prophylactic antibiotics. The incidence
      of infectious complications was the same in the two groups; however, there was an
      association between obliterative bronchiolitis and pulmonary infections. One of
      the patients with CF with P. cepacia died as a result of this organism. None of
      the patients with CF required treatment for Aspergillus post-transplant. We
      conclude that patients with CF, despite the presence of airway pathogens, are at
      no greater risk of infectious complications after LT than are other patients.

PMID- 7516253
TI  - [The hospital as a miniature corporation. The concept of organizational culture
      as root metaphor between quality and quantity of care].

PMID- 7516252
TI  - In vivo measurement of neutrophil activity in experimental lung inflammation.
AB  - Positron emission tomography (PET) was used to quantify 18fluorodeoxyglucose
      (18FDG) uptake in rabbits with experimental pneumonitis localized to the right
      upper lobe. In Streptococcus pneumoniae-induced pneumonia, which causes a
      profound inflammatory response lasting several days before it resolves, 18FDG
      uptake was pronounced at 15 h after the onset of inflammation, but by 48 h there
      was little uptake. In bleomycin injury, which progresses from an acute
      inflammatory stage to chronic inflammation and scarring, 18FDG uptake detectable
      by PET persisted for up to 21 d. Autoradiography of histologic sections after
      intravenous administration of [3H]deoxyglucose 15 h after streptococcal
      instillation and 2 wk after bleomycin instillation showed that, in both models,
      deoxyglucose uptake was localized to neutrophils. In the streptococcal model
      there was little 18FGD signal at 6 h, when major neutrophil migration occurs. At
      15 h, [3H]deoxyglucose-labeled neutrophils were present in the airspaces but not
      in the alveolar septa, suggesting that the deoxyglucose signal reflected a
      postmigratory neutrophil event, probably the respiratory burst. Thus, PET of
      18FDG uptake may provide a novel and readily repeatable, noninvasive approach to
      the in vivo study of neutrophil activity at otherwise inaccessible sites.

PMID- 7516250
TI  - Physiologic responses and histamine release after nasal antigen challenge. Effect
      of atropine.
AB  - We enrolled nine allergic subjects in a double blind, placebo-controlled study to
      examine the effect of premedication with 0.6 mg of atropine on nasal antigen
      challenge. The challenge consisted of unilaterally stimulating the nasal septum
      with diluent followed by three increasing doses of antigen and recording
      responses bilaterally. Sneezes, symptoms, and nasal airway resistance (NAR) were
      recorded. Secretions were collected using preweighed filter paper discs and
      histamine was measured. Antigen challenge with the subjects on placebo led to
      significant dose-dependent increases in sneezes, symptom scores, ipsilateral and
      contralateral secretion weights, ipsilateral NAR, and total amount of ipsilateral
      histamine (p < 0.05 versus diluent). Bilaterally applied atropine led to
      significant inhibition of ipsilateral and contralateral nasal secretions as well
      as rhinorrhea scores (p < 0.05 versus placebo) but had no significant effect on
      other parameters. Challenge after atropine premedication led to higher increases
      in histamine concentration than placebo (p < 0.01). These results suggest that
      parasympathetically stimulated fluids did not contain histamine and diluted the
      histamine released by mast cells. To support this hypothesis, we challenged the
      same subjects with methacholine. The concentration of histamine decreased and was
      significantly lower than after challenge with antigen (p < 0.01). The data
      suggest that: (1) histamine is released locally at the site of antigen challenge,
      (2) the volume of glandular secretions is primarily controlled by parasympathetic
      stimulation, and (3) the total amount of a mediator recovered in a fixed time
      interval best reflects the underlying pathophysiologic events.

PMID- 7516254
TI  - Involvement of neurokinins in the non-cholinergic response to activation of 5-HT3
      and 5-HT4 receptors in guinea-pig ileum.
AB  - 1. The involvement of neurokinins in the non-cholinergically-mediated contractile
      response induced by stimulation of 5-HT3 and 5-HT4 receptors has been examined in
      the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum. 2.
      The 5-HT3 receptor agonist, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT), showed
      a lower potency in this preparation than the more selective 5-HT4 receptor
      agonist 5-methoxytryptamine. The effect of both drugs was markedly reduced by
      atropine. 3. Substance P (SP) and neurokinin B (NKB) produced biphasic
      concentration-response curves in the preparation. Neurokinin A (NKA), the NK1
      receptor agonist, [Sar9,Met(O2)11]SP and the NK3 receptor agonist, senktide
      yielded monophasic concentration-response curves. 4. After desensitization of the
      NK1 receptor with SP or [Sar9,met(O2)11]SP, in the presence of atropine, the
      contractile response to 2-methyl-5-HT was entirely blocked. Desensitization of
      NK3 receptors with NKB, also in the presence of atropine, fully suppressed the 5
      HT4 receptor-mediated contraction evoked by 5-methoxytryptamine. 5. In
      preparations prelabelled with [3H]-choline, SP produced a concentration-dependent
      increase in tritium overflow, an index of [3H]-acetylcholine release, while an
      inverse relationship was found with NKB. At low neurokinin concentrations, the
      releasing effect of NKB was much more marked. 6. It is suggested that in the
      response to 5-HT3 receptor stimulation, there is a role for SP and acetylcholine.
      NKB appears to be preferentially involved in the release of acetylcholine
      elicited by stimulation of 5-HT4 receptors.

PMID- 7516255
TI  - Inhibition of olfactory cyclic nucleotide-activated current by calmodulin
      antagonists.
AB  - 1. In amphibian olfactory receptor neurones, much of the depolarizing current in
      response to odours is carried by cationic channels that are directly gated by
      cyclic AMP. The effects of four calmodulin antagonists on the cyclic AMP
      activated receptor current were studied in single olfactory cilia of the frog. 2.
      Two antagonists, W-7 and trifluoperazine, were potent and reversible inhibitors
      of the cyclic AMP-activated current. IC50 values were 5 microM for W-7 and 13
      microM for trifluoperazine. A third antagonist, calmidazolium, irreversibly
      blocked the current. The fourth, mastoparan, had little effect. 3. Calmodulin was
      unable to reverse the effects of W-7 and trifluoperazine, suggesting that these
      inhibitors act directly on the cyclic AMP-gated channels. 4. Neither W-7 nor
      trifluoperazine inhibited a Ca(2+)-activated Cl- current which also contributes
      to the odorant response. These compounds thus allow the two components of the
      olfactory receptor current to be discriminated.

PMID- 7516256
TI  - Effect of nitric oxide synthase inhibition on long-term potentiation at
      associational-commissural and mossy fibre synapses on CA3 pyramidal neurones.
AB  - 1. The sensitivity of long-term potentiation (LTP) to nitric oxide synthase (NOS)
      inhibition was determined for two synaptic input systems onto CA3 pyramidal
      neurones the LTP of which display differential sensitivity to N-methyl-D
      aspartate (NMDA) receptor antagonists: the fimbrial input which activates the
      associational-commissural synapses on the distal apical dendrites and the mossy
      fibre input which synapses on the proximal apical dendrites of CA3 pyramidal
      neurones. 2. Following high-frequency stimulation (HFS) of the fimbrial input,
      average e.p.s.p. amplitude increased by 92.4 +/- 22.0% (mean +/- s.e.mean; n = 6
      cells) when compared to the pre-HFS average. In the presence of 100 microM N
      omega-nitro-L-arginine methyl ester (L-NAME), the enhancement was reduced
      significantly to 32.2 +/- 11.6% (n = 5 cells; P < 0.05). In the presence of 300
      microM L-NAME, the inhibition was more complete, with post-HFS e.p.s.p. amplitude
      increasing an average 6.2 +/- 9.3% (n = 7 cells, P < 0.05). 3. Following high
      frequency stimulation of the mossy fibre input, average e.p.s.p. amplitude
      increased by 57.9 +/- 13.0% (n = 6 cells) when compared to the pre-HFS average.
      The presence of 100 microM L-NAME had no significant effect on the enhancement,
      averaging 63.6 +/- 5.9% (n = 4 cells; P > 0.05). Similarly, increasing the
      concentration of L-NAME to 300 microM had no significant effect on the
      potentiation, with the post-HFS amplitude increasing by an average 55.6 +/- 9.5%
      (n = 5 cells, P > 0.05). 4. These results suggest that LTP at associational
      commissural synapses (fimbrial input) is significantly depressed in the presence
      of the NOS inhibitor L-NAME, while mossy fibre LTP is unchanged.

PMID- 7516257
TI  - New possibilities for cancer therapy with advances in cancer immunology.
AB  - There has been progress over the last decade in addressing three questions: Are
      there cancer-associated antigens that could be targets for immunotherapy? Can the
      human immune system recognize cancer-associated antigens? Can an anti-cancer
      immune response affect cancer cells and lead to increased survival? Results from
      animal model studies have been interpreted by optimists as encouraging, and by
      pessimists as being irrelevant to human cancer. Earlier studies on "cancer
      vaccines" utilized heterogeneous cell extracts of cell components. Monoclonal
      antibodies have enabled identification of relevant cancer-associated antigens or
      epitopes, such as the ganglioside GM2, the carbohydrates TF and STn, and the
      peptide sequences of MUC-1. In parallel with research on immune adjuvants and
      measures designed to inhibit suppressor activity, these epitopes are being tested
      for their potential in the immunotherapy of solid tumors. It is clear that some
      of these cancer-associated epitopes are immunogenic in humans. Mixed responses
      may relate to cancer heterogeneity and may indicate the importance of multi
      epitopic vaccines. Responses are encouraging, but are they relevant? Prolonged
      disease stability challenges us to re-think the goals of cancer therapy. Recent
      advances in the knowledge of the effect of cytokines on tumor antigen expression
      and the regulation of the immune response, coupled with advances in active
      specific immunotherapy, provide hope that biomodulation may become an important
      part of the therapy of solid tumors in the next century.

PMID- 7516258
TI  - Delayed expression of c-fos protein in rat hippocampus and cerebral cortex
      following transient in vivo exposure to hypoxia.
AB  - The time course of c-fos protein expression after hypoxia was examined in rat
      hippocampus and cerebral cortex using an immunohistochemical method. The rats
      were exposed to in vivo hypoxia for 30 min in a chamber containing 5% O2 and 95%
      N2. Immediately after the treatment, c-fos protein-like immunoreactivity was
      observed in the granule cell layer of the dentate gyrus. The change was
      transient, and the density of immunoreactive cells returned quickly to a control
      level 3 h after the exposure. However, the density of positive cells was again
      increased 1 day after hypoxia and reached the maximum 7 days after. In the
      cerebral cortex, on the other hand, no change was detected in the pattern of
      staining at any time, with an exception on 21 days after hypoxia. At this period,
      positively stained neurons were significantly increased in both density and
      intensity throughout the entire extent of the cerebral cortex including the
      cingulate gyrus. These results clearly indicate that hypoxia induces different
      patterns of c-fos protein expression among various regions of the brain. The
      biphasic pattern seen in the dentate gyrus as well as the delayed expression in
      the cerebral cortex may be related to delayed neuronal damages induced by
      hypoxia.

PMID- 7516259
TI  - A study of tachykinin-immunoreactivity in the cat visual cortex.
AB  - The localization of tachykinin-immunoreactivity in the cat visual cortex (area
      17) was investigated using immunohistochemical methods. Strong laminar
      specificity was observed, with immunoreactivity highest in layer V, followed by
      layers I, VI, II and III, and the lowest density in layer IV. Most of the
      immunoreactive product was localized in neuronal processes. A few immunopositive
      cell bodies were also present. The immunopositive neurons were non-pyramidal,
      multipolar, or bipolar in shape, and mostly found in layer V. There were
      particularly dense immunopositive fibers and varicosities around somata in layer
      V. These may represent tachykinin-containing presynaptic terminals (boutons). The
      results provide anatomical evidence that tachykinins may primarily affect layer V
      neurons in the cat visual cortex.

PMID- 7516261
TI  - A toxin from the venom of the predator snail Conus textile modulates ionic
      currents in Aplysia bursting pacemaker neuron.
AB  - Conus textile crude venom and a peptide component ('King Kong' toxin) purified
      from this venom, alter membrane excitability of Aplysia neurons. Venom, applied
      to the medium bathing an abdominal ganglion, changes dramatically the electrical
      activity of bursting pacemaker neuron. The effects on bursting neuron R15 was
      examined in current-clamp and voltage-clamp modes. A dual phase effect of both
      the venom and the purified toxin were observed. The first phase starts
      immediately after venom or toxin application and is observed as an increase in
      membrane excitability, resulting in an enhancement of bursting. The second phase
      begins about 15 min later and consists of a long-lasting hyperpolarization. The
      dual phase effect of the venom and the toxin persists even when synaptic input is
      eliminated either by axotomy, or by recording from freshly dissociated neurons or
      from neurons in primary cell culture. The ionic currents affected are an inward
      current, INSR, which is activated upon depolarization and an anomalously
      rectifying potassium current, IR, which is activated upon hyperpolarization. In
      the first phase of toxin action INSR is increased. In the second phase both the
      venom and the toxin block INSR and increase IR. The toxin effects may be due to
      complex alteration of one or more second messenger cascades rather than a direct
      action on ion channels.

PMID- 7516260
TI  - Adrenalectomy increases the number of substance P and somatostatin immunoreactive
      nerve cells in the rat lumbar dorsal root ganglia.
AB  - Using an immunocytochemical technique we have analyzed changes in substance P,
      somatostatin, calcitonin gene-related peptide, and galanin immunoreactivity
      pattern in the rat dorsal root ganglia. After 7 days of adrenalectomy, sham
      operated rats were compared with adrenalectomized animals either receiving a
      daily intraperitoneal injection of 10 mg/kg b.wt. corticosterone or vehicle.
      Three lumbar ganglia from each animal were blocked, serially cut, and
      immunostained for each neuropeptide by means of the biotin-avidin-peroxidase
      technique. A systematic sampling of immunoreactive ganglion cells was performed
      and the sample number of immunoreactive ganglion cells was calculated. After
      adrenalectomy, the number of substance P and somatostatin immunoreactive ganglion
      cells markedly increased ((means +/- S.E.M.): 245 +/- 68 versus 123 +/- 12 for
      sham operated animals, P < 0.01 (substance P) and 42 +/- 8 as compared to 22 +/-
      9 for sham operated animals, P < 0.01 (somatostatin)). No significant changes
      were found in the number of calcitonin gene-related peptide and galanin
      immunoreactive cells after adrenalectomy. These results suggest that adrenal
      steroid hormones may reduce the synthesis of both substance P and somatostatin in
      the dorsal root ganglion cells. Daily treatment with a high dose of
      corticosterone, mimicking its serum levels after stress, failed to prevent the
      increase of peptide contents after adrenalectomy. These observations also
      indicate that a tonic action of corticosterone on mineralocorticoid receptors may
      be crucial for peptide regulation in the spinal ganglia. These results may be of
      relevance to adrenalectomy induced changes in sensory mechanisms, neurogenic
      inflammation and pain transmission and to a role of substance P and somatostatin
      in these processes.

PMID- 7516262
TI  - The New American Joint Committee on Cancer and International Union Against Cancer
      TNM classification of prostate cancer. Clinicopathologic correlations.
AB  - BACKGROUND: The 1992 American Joint Committee on Cancer and International Union
      Against Cancer TNM classification system for prostate cancer includes categories
      for the increasingly common nonpalpable cancers detected by serum prostate
      specific antigen (PSA) levels and transrectal ultrasonography (TRUS), but few
      details have been published about the pathologic features and prognosis of such
      cancers. METHODS: We analyzed the clinical and pathologic features of 400
      patients with clinical Stages T1-T3, NO or NX, M0 cancer treated with radical
      prostatectomy. We compared volume, grade, extension, and prognosis of cancers
      detected by PSA or TRUS to those detected by the traditional techniques of
      transurethral resection (TURP) or digital rectal examination. RESULTS: As
      clinical stage increased in the TNM classification, the volume, grade, and
      frequency of extraprostatic spread increased significantly. The 33 nonpalpable,
      nonvisible tumors detected because of an elevated PSA (T1c) were similar in size
      and frequency of extension to TURP-detected (T1a-b) cancers, but more often were
      poorly differentiated (52% vs. 22%) (P < 0.03). No T1c cancer has recurred to
      date. Nonpalpable T2 cancers detected by TRUS (n = 42) were significantly more
      likely (47% vs. 18%) to extend outside the prostate than were T1c cancers.
      Compared to palpable T2 cancers, TRUS-detected T2 cancers were smaller but were
      similar in grade, extension, and prognosis. T3 cancers were extensive and
      recurred rapidly; only 6% were confined to the prostate. In contrast, 24% of the
      T1 and 57% of the T2 cancers were not confined (> or = pT3), but only 6-9% of T1
      T2a cancers exhibited advanced pathologic features (seminal vesicle invasion or
      lymph node metastases), compared with 26% of the T2b-c cancers. CONCLUSION: The
      new TNM staging system provides appropriate new categories for inclusion of
      nonpalpable cancers detected by PSA and ultrasound. This new classification is
      logical and generally reflects the pathologic extent and prognosis of these
      tumors, although cancers in the advanced T2 categories are often more extensive.

PMID- 7516263
TI  - Transcatheter oily chemoembolization for hepatocellular carcinoma. A 4-year study
      of 127 French patients.
AB  - BACKGROUND: In Western countries, only a small proportion of patients with
      hepatocellular carcinoma (HCC) can be treated with surgical resection. For other
      patients, locoregional management by transcatheter oily chemoembolization seems
      to be useful and warrants evaluation. METHODS: One hundred and twenty-seven
      French patients with an inoperable HCC were treated by transcatheter oily
      chemoembolization. The efficiency of the treatment was assessed by a comparison
      of this group with a group of 127 untreated patients. Each patient of the treated
      group was matched closely with an untreated patient for all the main clinical,
      anatomic, and biologic features that characterize the spontaneous evolution of
      HCC. RESULTS: The overall probabilities of survival in the treated group were
      64%, 38%, 27%, and 27% at 1, 2, 3, and 4 years, respectively; those for the
      untreated group were 18%, 6%, and 5% at 1, 2 and 3 years, respectively (P <
      0.0001). The survival was significantly increased in patients with Okuda Stage I
      and II disease (P < 0.0001), but not in those with Stage III. Karnofsky and Child
      Pugh scores remained stable during the follow-up period and dropped only shortly
      before patients died. CONCLUSION: Transcatheter oily chemoembolization is an
      efficient treatment for unresectable HCC for the palliation of symptoms as well
      as for the prolongation of survival with a good quality of life.

PMID- 7516264
TI  - Detection of hepatocellular carcinoma-specific alpha-fetoprotein by isoelectric
      focusing.
AB  - BACKGROUND: Serum alpha-fetoprotein (AFP) is elevated in up to 80% of patients
      with hepatocellular carcinoma (HCC). Modestly raised AFP levels (10-400 ng/ml)
      are also found in patients with nonmalignant liver diseases. In the present
      study, isoelectric focusing of AFP was used to differentiate the AFP found in
      patients with HCC. METHODS: To establish the assay conditions, isoelectric
      focusing was performed on sera from 14 patients with HCC and 13 with nonmalignant
      liver diseases. Sera was also analyzed under coded conditions from 16 patients
      with HCC, 14 with chronic active hepatitis (CAH), and 6 with cirrhosis to
      determine the specificity and sensitivity of the assay in the diagnosis of HCC.
      RESULTS: Isoelectric focusing of sera from patients with HCC and various non
      malignant liver diseases identified AFP variants (AFP I-IV). All 14 patients with
      HCC had AFP variants I and III, and 7 of the 14 also had variant IV. When
      analyzed in the coded study 13 of the 16 cases of HCC were predicted correctly by
      the presence of AFP variants III or III and IV. AFP bands III and IV were not
      discernible in 12 of the 14 patients with CAH and 4 of the 6 with cirrhosis.
      CONCLUSION: Isoelectric focusing of sera from patients with HCC and nonmalignant
      liver disease identified two AFP variants apparently specific for HCC. In the
      setting of borderline elevation of AFP, this technique has a sensitivity of 81%
      and specificity of 85% for detecting the presence of bands III or IV and may
      prove suitable for use in a routine laboratory as a screening assay.

PMID- 7516265
TI  - Split genes and RNA splicing.

PMID- 7516266
TI  - Synthesis of 4-alkoxyaryl beta-D-glucopyranosides and their inhibitory effects on
      histamine release from rat peritoneal mast cells induced by concanavalin A.
AB  - The inhibitory effects of newly synthesized 4-alkoxyaryl beta-D-glucopyranosides
      on histamine release from rat peritoneal mast cells induced by concanavalin A
      were examined. A plot of hydrophobicity (k') against inhibitory activity of the
      compounds showed a distinct maximum, and 4-decyloxy-2,3,6-trimethylphenyl beta-D
      glucopyranoside was the most potent inhibitor among the tested compounds.

PMID- 7516267
TI  - Acute phase proteins and lipoprotein(a) in patients with severe
      hypercholesterolaemia and normal subjects.

PMID- 7516268
TI  - Disturbed immunoregulatory properties of the neuropeptide substance P on
      lymphocyte proliferation in HIV infection.
AB  - The neuropeptide substance P (SP) is known to increase cell-mediated immune
      responses in animal models and healthy subjects. Several studies have suggested
      an involvement of neuropeptides in the immunopathogenesis of some diseases. The
      study of the immunomodulatory effects of neuropeptides, namely SP, may represent
      a model for the analysis of immunoregulatory defects in HIV infection at the
      level of the interaction between the immune and nervous systems, both of which
      are known to be affected by the virus. In the present study, we investigate the
      possibility of a disturbance in the immunomodulatory properties of SP in HIV
      infection by analysing the effects of SP (10(-10)-10(-6) M) on the lymphocyte
      proliferative responses to concanavalin A (Con A) and phytohaemagglutinin (PHA)
      assessed by 3H-thymidine incorporation in peripheral blood lymphocytes from 34
      HIV-infected patients (16 asymptomatic (ASY)/persistent generalized
      lymphadenopathy (PGL); 18 ARC/AIDS) and in 37 healthy subjects. In ASY/PGL HIV
      infected patients, SP 10(-7) M was identified as the concentration inducing the
      maximal increase in the lymphocyte responses to Con A and PHA, similarly to what
      was observed in healthy subjects. In ARC/AIDS patients, SP appeared to inhibit
      the mitogenic responses, particularly those induced by Con A, in contrast to the
      effects found either in healthy subjects or in ASY/PGL patients. These results
      suggest the existence of an alteration in the in vitro immunomodulatory
      properties of SP in ARC/AIDS patients compared with healthy subjects and ASY/PGL
      patients. In conclusion, the unexpected finding of an inhibitory effect of SP on
      lymphocyte proliferation from ARC/AIDS patients justifies further investigation
      of the neuropeptide-dependent immunoregulatory systems in HIV infection.

PMID- 7516269
TI  - Adenovirus infection induces loss of HLA class I and CD3 antigens, but does not
      induce cell surface presentation of the La (SS-B) autoantigen.
AB  - Antibodies to the RNA polymerase III transcription termination factor La are
      frequently found in the serum of patients with various autoimmune diseases. The
      mechanisms by which autoimmune responses are evoked remain largely obscure, but
      the presentation of autoantigens on the cell surface during stress conditions has
      been reported as a possible factor. In this study we analysed the effects of
      adenovirus infection on the binding of anti-La antibodies to the surface of
      several human cell lines and on the levels of the membrane-expressed
      glycoproteins HLA class I, CD44 and the CD3 complex. In addition, we studied the
      relative amount and the intracellular distribution of the La protein as well as
      its association with the major species of non-coding virus-associated (VAI) RNA.
      While immunofluorescence patterns revealed a redistribution and possibly cell
      surface expression of the La protein during infection, this could not be
      confirmed by other techniques. In contrast, surface levels of HLA class I
      proteins and CD3 complex were severely affected. The data suggest that the
      subcellular distribution of the La protein is not detectably influenced by
      adenovirus infection.

PMID- 7516270
TI  - Molecular basis for antibody cross-reactivity between the hepatitis C virus core
      protein and the host-derived GOR protein.
AB  - The presence of antibodies reactive to a recently cloned host-derived antigen GOR
      is highly correlated with the presence of antibodies to the hepatitis C virus
      (HCV). We explored the molecular basis for this observation, and address the
      following question: are antibodies reactive with GOR19-27 (QKAKSNPNR) a result of
      a cross-reactivity triggered by the antigenic region at residues 9-17 of HCV core
      (RKTKRNTNR)? We compared the relative antibody avidity between antibodies
      reactive to both regions, and determined the residues essential for antibody
      binding using substitution peptide analogues. Of 96 sera assayed, 60 were found
      positive for anti-HCV, and of these 55 were found to react with HCV core. Twenty
      nine sera were found reactive to the GOR peptide, and these were all reactive to
      HCV core. In most cases the relative antibody avidity of antibodies reactive to
      GOR was higher for the HCV core peptide. In 21 of the GOR-reactive sera we were
      able to determine the essential residues for antibody binding. The essential
      residues in > 50% of all tested sera coincided with the well conserved residues
      Lys10, Lys12, Asn14, and Asn16. Also, reactivity to GOR was not related to any
      certain serotype of antibodies to HCV. Taken together, these findings explain at
      the molecular level the observed cross-reactivity between these two proteins,
      since sequence homology per se is not evidence for cross-reactivity.

PMID- 7516271
TI  - Some patients with anti-myeloperoxidase autoantibodies have a C-ANCA pattern.
AB  - Rapidly progressive glomerulonephritis with or without other signs of systemic
      vasculitis is often accompanied by antibodies to myeloperoxidase. Such antibodies
      normally produce a perinuclear pattern on ethanol-fixed neutrophils (perinuclear
      anti-neutrophil cytoplasm antibodies (P-ANCA)) at indirect immunofluorescence. We
      report here sera from three patients that are anti-myeloperoxidase-positive in
      ELISA that instead produce a cytoplasmic pattern (classical anti-neutrophil
      cytoplasmic antibodies (C-ANCA)), a pattern normally seen in conjunction with
      antibodies to proteinase 3. These sera did not react with proteinase 3. For two
      of the sera the specificity of the anti-myeloperoxidase reaction was confirmed
      with inhibition-ELISA experiments and with immunoblotting. A mouse anti
      myeloperoxidase MoAb that produces a cytoplasmic pattern is also described.
      Competition ELISA experiments show that this antibody and anti-myeloperoxidase
      sera with cytoplasmic pattern recognize epitopes that are separate from epitopes
      recognized by another perinuclear pattern producing anti-myeloperoxidase MoAb.
      'Cytoplasmic pattern' epitopes as well as 'perinuclear pattern' epitopes can be
      found on all three major myeloperoxidase isoforms, after separation by ion
      exchange chromatography. Affinity chromatography, using the cytoplasmic pattern
      producing anti-myeloperoxidase monoclonal antibody, shows that the epitope
      recognized by this MoAb is present on all myeloperoxidase molecules. This epitope
      is not confined to any special subpopulation. These findings indicate that all
      myeloperoxidase do not relocate after ethanol fixation, and that C-ANCA and P
      ANCA epitopes exist simultaneously on the same myeloperoxidase molecule. We
      propose that the two immunofluorescence patterns arise due to different
      availabilities of the epitopes in the microenvironment where myeloperoxidase is
      present.

PMID- 7516272
TI  - Fine specificity of the murine immune response to SV40 large tumour antigen
      utilizing synthetic peptides that define selected epitopes.
AB  - Baculovirus-derived recombinant simian virus 40 large tumour antigen (SV40 T-ag)
      was used to immunize BALB/c, C57Bl/6 and CB6/F1 mice and their anti-SV40 T-ag
      antibody responses were examined for the ability to bind synthetic peptides
      representing six predicted B cell epitopes on SV40 T-ag. In C57Bl/6 mice, anti
      SV40 T-ag antibodies failed to bind any of the six SV40 T-ag peptides. However,
      the antibody responses induced in both BALB/c and CB6/F1 mice recognized
      synthetic peptides corresponding to two distinct epitopes (amino acids 690-708
      and 660-679, respectively) associated with the carboxyl-terminal half of SV40 T
      ag. In addition, murine MoAbs (BALB/c) generated to native SV40 T-ag, and
      previously characterized as recognizing the carboxyl-terminus of SV40 T-ag by
      deletion mutant analysis, also bound the synthetic peptide (residues 690-708)
      defining the carboxyl-terminus of SV40 T-ag. These data indicate that the
      antibody responses induced in BALB/c and CB6/F1 mice by immunization with
      baculovirus-derived recombinant SV40 T-ag are capable of recognizing sequential
      carboxyl-terminal epitopes on SV40 T-ag defined by peptides 690-708 and 660-679,
      respectively. No statistically significant differences in anti-SV40 T-ag antibody
      titres were observed between the three inbred mouse strains. These data suggested
      that the fine specificities of the anti-SV40 T-ag responses as assessed by
      synthetic peptide binding were different in the three inbred strains of mice
      examined. Finally, in vivo tumour challenge studies comparing recombinant SV40 T
      ag with the two carboxyl-terminus peptide epitopes indicated that some tumour
      immunity was induced in BALB/c, but not CB6/F1 mice, by immunization with peptide
      690-708 conjugated to a carrier protein. These studies suggest that the carboxyl
      terminal region of SV40 T-ag represents a continuous sequential epitope involved
      in both the antibody response to SV40 T-ag and tumour immunity in BALB/c mice.

PMID- 7516273
TI  - Effects of ethanol consumption and withdrawal on B cell subpopulations in murine
      bone marrow.
AB  - We designed studies to examine the effects of ethanol consumption and withdrawal
      on the numbers of pre-B and B cells in murine bone marrow. Flow cytometric
      analysis of B220 and surface IgM expression on bone marrow cells revealed that
      consumption of ethanol by mice for 7 days led to a significant reduction in pre-B
      cells. The number of mature B cells in the bone marrow of these animals, however,
      did not differ from that of control mice. In contrast, examination of bone marrow
      obtained from mice at various times after withdrawal from ethanol showed
      significantly fewer numbers of mature B cells and an even greater loss of pre-B
      cells. This effect was seen for relatively long periods after withdrawal. These
      study findings are interpreted to suggest that ethanol consumption results in
      changes in the pre-B cell population in murine bone marrow. It also appears that
      withdrawal from ethanol results in more profound changes in the mature B cell
      population of the bone marrow than those that occur during ethanol consumption.

PMID- 7516274
TI  - Hepatitis-C virus (HCV) in peritoneal dialysis.

PMID- 7516275
TI  - Partial reversal of established bleomycin-induced pulmonary fibrosis by rh
      urokinase in a rat model.
AB  - Pulmonary fibrosis was induced in male Sprague-Dawley rats by intratracheal
      instillation of bleomycin. By 30 d post-bleomycin, the lungs exhibited elevated
      interstitial collagen levels. Thirty d after exposure to bleomycin, animals were
      further treated by intratracheal administration of phosphate-buffered saline
      (PBS) or 12,500 units of recombinant human urokinase (rh-UK). Three days later,
      the animals were sacrificed and the lungs fixed, sectioned, and assessed for
      fibrosis. The presence of interstitial collagen was quantitated using a BioQuant
      Image Analysis System (R and M Biometrics, Inc., Nashville, TN). Urokinase
      treatment of animals with established pulmonary fibrosis induced by exposure to
      0.5 units of bleomycin was found to diminish the collagen content of lungs to
      near control levels by 3 d post-UK treatment. By 36 d post-UK treatment (66 d
      post-bleomycin), values for interstitial collagen were again partially elevated,
      indicating that UK treatment interfered with established fibrosis but did not
      stop the bleomycin-mediated process. However, the extent of fibrosis was less
      than that observed in lungs from non-UK treated animals 66 d post-bleomycin. UK
      treatment initiated 63 d post-bleomycin exposure again revealed a decline in the
      extent of fibrosis, but the values did not return to baseline levels. A repeat of
      the short-term experiment with a higher dose of bleomycin (0.85 units) again
      revealed that UK treatment was effective in diminishing the extent of fibrosis
      from 22% to 12% collagen. These results indicate that exogenous UK may be an
      effective therapeutic modality in the treatment of pulmonary fibrosis induced by
      some stimuli or developing in association with diseases such as scleroderma.

PMID- 7516276
TI  - Cellular receptors for tenascin.

PMID- 7516278
TI  - Fine-needle aspiration cytology of metastatic basal cell carcinoma of the skin to
      the lung.
AB  - Metastatic basal cell carcinomas of the skin are rare. We present the cytologic
      features of a metastatic basal cell carcinoma to the lung diagnosed by fine
      needle aspiration biopsy. Cytologic examination revealed syncytial groups of
      relatively small cells with hyperchromatic, oval to spindle-shaped nuclei having
      high nuclear to cytoplasmic ratios. Immunocytochemical studies performed on the
      cell block sections revealed the malignant cells to be positive for cytokeratin
      (AE1/3) and negative for neuroendocrine markers, [neuron specific enolase (NSE)
      and chromogranin (Phe-5)]. We reviewed the literature related to metastatic basal
      cell carcinoma of the skin and discuss risk factors and mechanisms of metastatic
      spread. In addition, a discussion of the other entities that can enter into the
      differential diagnosis is presented along with the role of ancillary studies. To
      the best of our knowledge, we believe this is the first case report of the fine
      needle aspiration (FNA) cytology of a basal cell carcinoma metastatic to the
      lung.

PMID- 7516277
TI  - Screening for neural tube defects.
AB  - The birth prevalence of neural tube defects fell by 95% in England and Wales
      between 1970 and 1990 largely as a result of antenatal screening, subsequent
      diagnosis and selective abortion of affected pregnancies. Anencephaly can be
      diagnosed using ultrasound, whereas both amniotic fluid biochemistry and
      ultrasound are required for the diagnosis of spina bifida. Both methods have a
      false-positive rate of about two per 1000 when carried out in high-risk
      pregnancies. The diagnostic results are likely to be better if the two methods
      are used in parallel. Maternal serum alpha-fetoprotein screening at 16-18 weeks
      gestation can detect about 75% of pregnancies affected by spina bifida. Routine
      ultrasound anomaly screening, usually performed at 18-20 weeks gestation, can
      detect a similar proportion. New developments indicate that earlier, more
      accurate detection may be possible but more research will be needed before this
      can be established.

PMID- 7516279
TI  - Clue helping to distinguish hyalinizing trabecular adenoma from carcinoma of the
      thyroid in fine-needle aspirates.
AB  - Fine-needle aspirates from four hyalinizing trabecular thyroid adenomas stained
      with May-Grunwald-Giemsa showed a distinctive component of purplish red stromal
      deposits corresponding to accumulations of basement membrane material occurring
      in such tumors. Recognition of these deposits helps to prevent cytologic
      overdiagnosis of malignancy in this rare benign tumor, which has a number of
      traits in common with both papillary and medullary carcinoma of the thyroid.

PMID- 7516280
TI  - Presentation of a general algorithm to include effect assessment on secondary
      poisoning in the derivation of environmental quality criteria. 2. Terrestrial
      food chains.
AB  - In a previous study a simple algorithm was presented for effect assessment on
      secondary poisoning of birds and mammals. This algorithm (MPC = NOECfish
      eater/BCFfish) was drawn up by analyzing a two-step aquatic food chain (water
      fish-bird/mammal). The algorithm was used to test whether quality criteria set
      for surface water, based on effect assessment for aquatic organisms, constitute a
      "safe" level for secondary poisoning. The present study analyzes whether this
      algorithm can equally well be used for effect assessment in a terrestrial food
      chain. The pathway soil-earthworm-bird/mammal was used as an example for a
      terrestrial food chain. Literature data of six selected compounds (lindane,
      dieldrin, DDT, PCP, cadmium, and mercury) on both bioconcentration factors for
      earthworms and toxicity data for birds and mammals were studied. Important
      differences were found between BCFs for this terrestrial pathway and BCFs for the
      aquatic pathway analyzed in the previous study. It was found that BCFs for
      earthworms were more dependent on soil-related properties than on compound
      specific properties. Hence, it was concluded that the algorithm MPC = NOECworm
      eater/BCFworm can be used only for effect assessment on terrestrial food chain in
      defined situations. By calculating maximum permissible concentrations for
      secondary poisoning (MPCsp) for a standard soil situation and comparing these to
      MPCs for soil organisms, it was concluded that secondary poisoning could be a
      critical pathway for cadmium and methyl mercury. For methyl mercury secondary
      poisoning in an aquatic food chain was also a critical pathway. Secondary
      poisoning of fish-eating birds and mammals is not likely to occur for cadmium at
      concentrations in water below the MPC calculated for aquatic organisms.

PMID- 7516281
TI  - A field study of environmental impacts at a bleached kraft pulp mill site on the
      Baltic Sea coast.
AB  - The rate of technical development in bleaching of chemical pulp and the upgrading
      of process control and wastewater treatment systems in the pulp industry have
      been extremely rapid over the past few years. When assessing the environmental
      impacts of bleached kraft pulp mill effluents (BKMEs), it is therefore more
      important than ever to carefully characterize the bleaching process, the
      composition of the treated effluent, and the degree of exposure of sensitive
      target organisms in the receiving water body. These requirements have not always
      been fulfilled in previous reports on biological effects of BKMEs in Scandinavia.
      This work presents the results of a comprehensive field study of the impacts of a
      350,000-tonne kraft mill, bleaching softwood and hardwood pulp in campaigns
      according to the sequence O(D25,C70+D5)(EOP)D(EP)D. The effluent is treated in an
      aerated lagoon with a mean retention time of 8-9 days, practically eliminating
      chlorate and resin acids, and reducing the discharge of adsorbable organic
      halogen (AOX) to an average of 1 t/day (1.3 and 0.4 kg/ADt for softwood and
      hardwood, respectively). The treated effluent is discharged through a 1.3-km-long
      diffuser, at a water depth of 9-12 m, into a well ventilated coastal area, giving
      a 1000-fold dilution within 3-4 km from the diffuser. The actual exposure of the
      coastal ecosystem to BKME components was determined by analysis of extractable
      organic chlorine in suspended solids and of conjugates of chlorophenolics in the
      bile of feral perch. Despite a major damage to the benthic communities that
      occurred about 10 years ago, and was due to large chlorate discharges at the
      time, no direct detrimental effects on benthic flora and fauna could be ascribed
      to the present BKME discharge. Instead, a clear recovery of the Fucus community,
      although not yet completed, could be demonstrated. Studies of the composition,
      abundance and biomass of the fish community, the recruitment and survival of fish
      fry, and the physiological status of perch, using a set of biomarkers, revealed
      that even in the most BKME-exposed area, only minor effects were detected. These
      effects were related to eutrophication/enrichment rather than to the action of
      toxic substances. The general effect picture, thus, was essentially of a
      different type than the one recorded in previous studies of mills, which used
      older technology and less effective process and effluent treatment control, and
      which were discharging into enclosed, shallow bays of the Baltic Sea.

PMID- 7516282
TI  - Toxic effects of pollutants on the mineralization of chloroform in river
      sediments.
AB  - The influence of pollutants on the formation of 14CO2 from 3 micrograms/liter
      labeled chloroform was studied in anaerobic Dutch river sediments. All
      incubations were performed under anaerobic conditions. Addition of toxicants to
      sediment microcosms showed logistic dose-effect curves. The concentration giving
      10% inhibition of the chloroform mineralization rate (IC10) was derived from
      these dose-effect curves. The IC10 values of added cadmium, chloropyrifos,
      benzene, mercury, or 1,2-dichloroethane were 1300, 1300, 140, 90, and 0.07 mg/kg
      dry sediment, respectively. Mud samples taken at different dates from the same
      site indicated a significantly different sensitivity to added pentachlorophenol
      and zinc. The IC10 of added pentachlorophenol was 150 mg/kg in one and 15 mg/kg
      in another sample. Chloroform-mineralizing bacteria are very sensitive to
      addition of zinc. The IC10 of added zinc was 700 mg/kg for one sample and 11
      mg/kg for another sample of the sediment which contained a background
      concentration of 800 mg Zn/kg. Therefore, a partial inhibition of the
      mineralization of chloroform by the high concentrations of zinc present in Dutch
      river sediments cannot be excluded. The high concentration of zinc might cause
      persistence of otherwise biodegradable pollutants in Dutch sediments.

PMID- 7516283
TI  - Some effects of elevated levels of chromium (III) in sediments to the Mullet
      Chelon labrosus (R.).
AB  - An investigation into the possible toxic effects of elevated levels of chromium
      (III) in estuarine sediments as a result of leather tanning operations was
      conducted in parallel to a control study. The gray mullet Chelon labrosus (R.),
      which feeds directly on sediments, was monitored in a field study and in an
      aquarium experiment. Growth, mortality, gross tissue damage, and liver
      bioaccumulation were assessed. Growth was found not to be adversely affected by
      the elevated chromium levels in either field or aquarium studies and no
      macroscopic physiological damage was detected. In the aquarium experiment of 2
      month duration, there were no mortalities, although significant bioaccumulation
      was measured in the livers of exposed mullet (P < 0.01). In contrast, the
      concentrations of chromium in the livers of mullet sampled from the contaminated
      site were not significantly elevated compared to those of controls. It is
      suggested that the levels of chromium in the estuary are not overtly toxic to
      mullet and, although short-term accumulation occurs, long-term exposure appears
      to lead to a stabilization in liver chromium levels.

PMID- 7516284
TI  - An outdoor replicated artificial stream system: design, operating conditions, and
      initial invertebrate colonization.
AB  - The design and operating conditions of an outdoor replicated stream system are
      described. The facility is composed of a long inlet stream, a header weir which
      diverts inflowing water to six artificial stream channels (each 45 m long and 40
      cm wide), a settlement pond at the end of the channels, and an outlet stream
      which diverts the water back to an irrigation channel. Flow regulation is
      achieved by "V-notched" gates at the head of each stream and depth by a second
      set of gates at the end of each stream. Physicochemical conditions were monitored
      over a 260-day period and even though significant temporal variation was
      detected, little between-stream variation was observed for most parameters.
      Small, but significant, between-stream differences in dissolved oxygen and pH
      were detected but were attributed to sampling procedure rather than real between
      stream differences. A relatively rich invertebrate fauna colonized the streams.
      Invertebrate densities increased rapidly after initiation of flow and stabilized
      after 38 days. Chironomoid midge larvae were numerically the most important taxa,
      although the proportion of total density contributed by this group changed
      significantly with time. Taxon richness, chironomid taxon richness, diversity,
      and eveness also increased with time until a stable point was reached after 90
      days of flow. No significant between-stream difference in any of these parameters
      was detected suggesting that colonization dynamics were similar in each stream.

PMID- 7516285
TI  - Accumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents by double-crested
      cormorant (Phalacrocorax auritus, Pelicaniformes) chicks in the North American
      Great Lakes.
AB  - Concentrations of polychlorinated biphenyls (PCBs), and 2,3,7,8-tetrachlordibenzo
      p-dioxin equivalents (TCDD-EQ) were determined in eggs and chicks of double
      crested cormorants (DCC) which were collected in 1989 from eight locations in the
      Laurentian Great Lakes. The mean biomagnification factor (BMF) from forage fish
      to eggs was found to be 31.3. Absolute and relative concentrations as well as
      rates of accumulation of total concentrations of PCBs and TCDD-EQ were measurable
      in all of the samples. The concentrations of both PCBs and TCDD-EQs decreased
      immediately upon hatching of chicks, due to growth dilution. Initial decreases in
      absolute masses of TCDD-EQ in chicks were also observed, which indicates that
      there can be significant elimination of these compounds during early development.
      The initial rates of accumulation by chicks were dependent only on the mass of
      fish consumed. After the chicks began thermoregulating, the rates of
      accumulation, expressed as a concentration, normalized to body weight, became
      greater. Rates of accumulation of both PCBs and TCDD-EQ were correlated with
      their respective concentrations in forage fish consumed by the chicks. The
      relative potency, expressed as the ratio of the concentration of TCDD-EQ to that
      of total PCBs was calculated to determine if there was significant trophic-level
      enrichment of the TCDD-EQs, relative to total concentrations of PCBs. A
      significant enrichment was observed at the more and less contaminated locations,
      but the degree of enrichment was greater at the less contaminated locations (26
      vs 72 micrograms/g).

PMID- 7516286
TI  - Toxicity of metals on Daphnia magna and Tubifex tubifex.
AB  - The toxicity of Hg2+ [HgCl2], Cr6+(1) [(NH4)2CrO4], Cr6+(2) [CrO3], Cd2+
      [CdCl2.2,5H2O], Pb2+ [Pb(CH3COO)2.3H2O], and As5+ [Na2HAsO4.7H2O] on the
      sensitivity and survival of Daphnia magna and Tubifex tubifex has been studied.
      All test metals were dissolved and determined under standardized conditions
      (dilution water, Bringmann and Kuhn, 1982) and 96 hr LC50 for T. tubifex and 48
      hr LC50 for D. magna were compared in rank orders toxicity. For D. magna rank
      order toxicity was Hg2+ > Cr6+(2) > Cd2+ = Cr6+(1) > Pb2+ > As5+ and for T.
      tubifex it was Hg2+ > Cd2+ > Cr6+(2) > Cr6(1) > Pb2+ > As5+. D. magna was a more
      sensitive organism than T. tubifex and its LC50 values for all metals were
      several times lower than LC50 values for T. tubifex. Correlation between toxicity
      of various metals and biological subjects may be useful in predicting toxicity to
      various biologically important organisms connected with food chains.

PMID- 7516287
TI  - Modulation of protein metabolism in selected tissues of the crab, Oziotelphusa
      senex senex (Fabricius), under fenvalerate-induced stress.
AB  - Crabs, Oziotelphusa senex senex, were exposed to sublethal concentration (0.2
      ppm) of fenvalerate, and changes in the protein metabolism of hepatopancreas and
      muscle were investigated. The levels of total and soluble proteins were
      decreased, whereas the levels of the free amino acids and activity levels of
      protease, alanine transaminase, aspartate transaminase, and glutamate
      dehydrogenase were significantly increased in the tissues of crabs exposed to
      fenvalerate. The changes were more pronounced with an increase in the period of
      exposure. The possible adaptive significance of these changes during fenvalerate
      intoxication in the crab is discussed.

PMID- 7516288
TI  - The cell biology of bone growth.
AB  - The field of bone cell biology is clearly of relevance to the problem of stunting
      in children, as in the final analysis the cells of the growing long bone are the
      ultimate 'regulators'. It is the alterations in the functions of these cells that
      manifests as a reduction in height. Normal longitudinal growth is achieved by the
      coordinated recruitment, proliferation, differentiation, maturation and eventual
      death of the cells of growth plate and bone. Cellular activity is closely
      regulated by endocrine factors acting directly or indirectly, with factors
      produced locally and stored within the bone and cartilage microenvironment having
      a critical role in intercellular communication. Disruption of any of these
      processes can lead to growth disturbances, since it only requires a defect in a
      single gene to have profound effects. Studies in recent years have shed light on
      the biochemical and molecular effects of cytokines and growth factors and have
      shown that these regulatory molecules may mediate the effects of certain hormones
      important in controlling growth. However, the complex interrelationship of these
      molecules is still not clear. Notwithstanding, understanding of the mechanisms
      involved in bone remodelling is increasing, as this area attracts much research
      because of the high incidence of metabolic bone disease in Western society.
      Although studies of adult bone remodelling are of relevance, there is a
      requirement for increased research directed specifically at the mechanisms of
      endochondral ossification and its regulation. Longitudinal bone growth is a
      challenge to the cell biologist, since it is an accelerated cycle of cellular
      division and differentiation, within which it is not easy to separate events
      temporally and spatially. In addition, different regulatory mechanisms are
      probably important at different stages of growth. Another difficulty impeding
      progress in this field is the lack of appropriate animal models for research.
      Much information has come from studies involving rodents, and species differences
      must always be taken into account. Larger mammals such as the growing piglet or
      the calf are probably more appropriate for the study of postnatal longitudinal
      growth in man. If the mechanisms of stunting are to be established at a cellular
      level, a number of approaches need to be considered. Studies need to be designed
      using more appropriate animal models, and conditions such as nutritional intake,
      immunological challenges, chronic intestinal diseases and mechanical loading need
      to be manipulated. Any effects on longitudinal growth may then be studied
      temporally and correlated with non-invasive measurements including assays of
      hormones, cytokines, growth factors and proteins known to regulate their
      activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7516289
TI  - New cell biological applications of the laser microbeam technique: the
      microdissection and skinning of muscle fibers and the perforation and fusion of
      sarcolemma vesicles.
AB  - In a novel approach, the laser microbeam technique was used to selectively
      perforate the sarcolemma of skeletal muscle fibers, to prepare fragments of
      myofibrillar bundles of very small dimensions, and to induce fusion of sarcolemma
      vesicles. Using a highly focused UV laser microbeam with an effective beam
      diameter of down to 0.5 micron, very small (< 3 microns) myofibrillar fragments
      with an intact sarcomere striation pattern were obtained. When small amounts of
      Ca2+ were released in the vicinity of such a fragment by laser-photolysis of the
      photolabile compound Ca(2+)-nitr-7 the bundle shortened due to the development of
      calcium-activated force. We also show that very small selected areas from
      myopathic single muscle cells can be dissected with a precision unmatched by
      other current techniques. The microbeam was also used to remove very small
      patches of the sarcolemma of murine skeletal muscle fibers so giving diffusional
      access to the myoplasmic interior and thus resulting in a "skinning" of the
      fiber. To ensure that such laser-skinned fiber segments were physiologically
      intact we determined the Ca(2+)-activated force and caffeine-induced Ca(2+)
      release from the sarcoplasmic reticulum. The fibers showed normal characteristics
      for force production, Ca(2+)-release and uptake by the sarcoplasmic reticulum. To
      test the effects of the laser microbeam on the muscle membrane directly, we
      prepared sarcolemma vesicles of skeletal muscle fibers. The vesicles could be
      selectively perforated with single laser pulses to allow entry of fluorescein
      isothiocyanate (FITC)-dextran as a fluorescent marker. Adjacent vesicles were
      caused to fuse by a few pulses at low intensity of the laser microbeam.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7516291
TI  - Evidence that FK506 alleviates ischemia/reperfusion injury to the rat liver: in
      vivo demonstration for suppression of TNF-a production in response to
      endotoxemia.
AB  - The mechanism by which FK506 (FK) prevents hepatic injury induced by
      ischemia/reperfusion was studied. Adult Sprague-Dawley rats were subjected to 60
      min normothermic liver ischemia. Animals were divided into two groups: group I,
      controls, saline vehicle treatment; group II, FK treatment. FK (1 mg/kg/day,
      p.o.) was given for 4 consecutive days prior to inducing ischemia. In addition to
      a survival study, plasma levels of endotoxin and serum activities of tumor
      necrosis factor-alpha (TNF) and aspartate aminotransferase (AST) were assessed in
      the blood collected from suprahepatic vena cava. Results showed: (1) FK therapy
      significantly improved 7-day survival (80.0%) compared with nontreated animals
      (50.0%, p < 0.05); (2) both TNF and endotoxin were elevated following
      reperfusion, reaching maximum values at 3 h after reperfusion (217.0 +/- 40.6 and
      280.5 +/- 31.4 pg/ml, respectively, in the control; mean +/- SEM), and (3) serum
      activities of TNF and AST following reperfusion were substantially suppressed
      with FK treatment, whereas FK did not reduce the rise in endotoxin. These
      findings suggest that suppression of TNF production in response to endotoxemia
      might account at least in part for the protective effect of FK against ischemia
      induced hepatic injury.

PMID- 7516292
TI  - Effect of verapamil and iloprost (ZK 36374) on endothelin release after
      mesenteric ischemia-reperfusion injury.
AB  - In this experimental study we studied the effect of verapamil and iloprost on
      endothelin release in ischemia/reperfusion (IR) injury of the rat intestine.
      Endothelin levels in the portal blood and malondialdehyde (MDA), PGE2, and LTC4
      levels in the intestinal tissue were determined. The MDA levels increased in the
      control group and this increase was reversed with iloprost, verapamil and both.
      The change in the LTC4 levels was insignificant between the groups. Iloprost
      reduced PGE2 and endothelin release, but verapamil was not as effective and no
      synergistic effect was encountered. The increased PGE2/LTC4 ratio was also
      reversed in the experimental groups, verapamil being less effective. Endothelin
      release seems to be related to both PGE2 levels and the PGE2/LTC4 ratio after
      mesenteric IR injury.

PMID- 7516290
TI  - Membrane traffic and sorbitol release during osmo- and volume regulation in
      isolated rat renal inner medullary collecting duct cells.
AB  - In response to hypotonic stress, cells of the inner medullary collecting duct
      (IMCD) undergo swelling followed by a regulatory volume decrease (RVD) and a
      transient release of organic osmolytes such as sorbitol. In this study, we tested
      the hypothesis whether membrane recycling is involved in the latter process.
      Therefore, the state of submembranal actin and the cellular uptake or release of
      the fluid-phase marker fluorescein isothiocyanate (FITC)-dextran (FD) were
      investigated as related to changes in membrane permeability for sorbitol. After
      exposure to hypotonic medium the submembranal actin web rapidly disaggregated but
      it started to reorganize after 5 min of incubation. The basal-lateral pole of
      IMCD cells showed a significant uptake of extracellular FD after 100 sec. After 5
      min, part of this fluorescence intensity had moved towards the cell center but
      the main part remained submembranal. Disintegration of the actin network by
      cytochalasin D diminished the uptake of FD during hypotonicity as did a permanent
      increase in intracellular calcium induced by ionomycin treatment. During a second
      osmotic stimulation of IMCD cells preloaded with FD, FD was released in a linear
      time course reaching a plateau after 1 min. Isotonic ionomycin treatment of
      preloaded cells also generated a rapid FD release during the first minute but
      induced a further 2-fold increase during the next 4 min. Under both conditions
      initial FD release was highly correlated with the simultaneously determined
      increase in sorbitol permeability. A similar strong correlation was found when
      different incubation temperatures were used (0 degree C, 15 degrees C, 37 degrees
      C). These results suggest that during exposure of IMCD cells to hypotonicity the
      submembranal actin web rapidly disintegrates, and "reserve" vesicles, probably
      containing sorbitol transporter, move to and fuse with the basal-lateral plasma
      membrane. The fusion causes a rapid increase in sorbitol permeability. These
      membrane areas are recovered by internalization, and the transport systems for
      sorbitol are concomitantly retrieved. In parallel to this internalization the
      submembranal actin filament network is rearranged. This process seems to be
      regulated by changes in intracellular calcium.

PMID- 7516293
TI  - Predominance of myeloid antigens in CD34-positive peripheral blood stem cells
      over those in bone marrow after administration of granulocyte colony-stimulating
      factor.
AB  - We analyzed the surface phenotype of CD34-positive (CD34+) cells in peripheral
      blood (PB) during the period of hematopoietic recovery following myelosuppressive
      chemotherapy. A significantly higher proportion of PB CD34+ cells coexpressed the
      CD13 and CD33 myeloid antigens (80.8%, 78.1%, respectively) than did BM CD34+
      cells (45.8%, 37.8%, respectively) (both p < 0.01). In particular, the CD13
      positivity of PB CD34+ cells harvested with granulocyte colony-stimulating factor
      (G-CSF) was significantly higher than that of those without G-CSF. Most of the PB
      CD34+ cells possessed the HLA-DR antigen, and less than 10% of the CD34+ cells
      coexpressed a mature cell antigen, such as CD14, GPA or Plt-1. The administration
      of G-CSF enhanced the appearance of significantly larger amounts of CD13+ 34+ and
      CD33+ 34+ cells (both p < 0.01). This G-CSF mobilization also resulted in an
      increased number of CD13- 34+ and CD33- 34+ cells and all types of colony-forming
      cells. On the other hand, macrophage colony-stimulating factor administration
      exerted little influence on the mobilization of PB CD34+ cells. Thus, G-CSF
      seemed to induce not only an expansion of circulating hematopoietic stem cells
      but also the myeloid differentiation of stem cells.

PMID- 7516296
TI  - The difficulties of researching prevention.

PMID- 7516294
TI  - Primary plasma cell leukaemia. A case report emphasizing some aspects of cellular
      adhesion molecules in plasmacytic proliferations.

PMID- 7516295
TI  - Adjuvant growth hormone treatment during in vitro fertilization: a randomized,
      placebo-controlled study.
AB  - OBJECTIVES: To explore the effect of recombinant, human GH on follicular
      development and oocyte retrieval after gonadotropin stimulation with the addition
      of GH or placebo to a standard IVF treatment regimen. Further, to investigate
      whether GH is a more effective adjuvant if the standard treatment regimen is
      preceded by GH injections. DESIGN: A randomized, double-blind, parallel, placebo
      controlled study. SETTING: The IVF unit at university hospital. PATIENTS: Forty
      normally ovulating women, age 25 to 38 years, with infertility because of tubal
      factors and being classified as "poor responders" with at least two previously
      performed and failed IVF attempts. INTERVENTIONS: Human, recombinant GH
      (Genotropin, Kabi Pharmacia, Uppsala, Sweden) or placebo (0.1 IU/kg body weight
      per day) was given SC as pretreatment during down regulation with GnRH and during
      stimulation with hMG according to the randomized protocol. MAIN OUTCOME MEASURES:
      Number of oocytes retrieved after stimulation, total amount of gonadotropin used,
      time required for stimulation, number of follicles developing, rate of
      fertilization, and cleavage in vitro. Further, the quality of embryos,
      development of the endometrium, rate of clinical pregnancy, and serum and
      follicular fluid (FF) concentrations of insulin-like growth factor I (IGF-I),
      insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 were
      estimated. RESULTS: The number of oocytes retrieved did not differ significantly
      between the groups, nor did the amount of hMG required for stimulation. The
      fertilization rate increased in patients who had received GH. Growth hormone
      caused a significant increase in serum and FF levels of IGF-I. An increase in
      serum IGFBP-3 could also be recorded in patients who had received GH. CONCLUSION:
      Although certain beneficial effects were noted in GH-treated patients, the
      overall results did not support GH as a clinically useful adjuvant treatment.

PMID- 7516297
TI  - Transdermal scopolamine for reduction of drooling in developmentally delayed
      children.
AB  - Ten developmentally delayed children with excessive drooling were randomized in a
      double-blind, placebo-controlled study to assess the efficacy and safety of
      transdermal scopolamine. Over half of the patients had a statistically
      significant reduction in drooling, and one-third had cessation of drooling, while
      wearing the scopolamine patch. This short-term study supports earlier reports of
      the safety and efficacy of transdermal scopolamine for reducing excessive
      drooling in developmentally disabled children.

PMID- 7516298
TI  - Subtle anomalies of the septum pellucidum and neurodevelopmental deficits.

PMID- 7516300
TI  - Mechanisms of methylmercury-induced neurotoxicity.
AB  - Mercury in both organic and inorganic forms is neurotoxic. Methylmercury (MeHg)
      is a commonly encountered form of mercury in the environment. Early
      electrophysiological experiments revealed that MeHg potently affects the release
      of neurotransmitter from presynaptic nerve terminals. Recently, the hypothesis
      that these alterations may be mediated by changes in the intracellular
      concentration of Ca2+ ([Ca2+]i) has been supported. MeHg alters [Ca2+]i by at
      least two mechanisms. First, it disrupts regulation of Ca2+ from an intracellular
      Ca2+ pool and second, it increases the permeability of the plasma membrane to
      Ca2+. MeHg also blocks plasma membrane voltage-dependent Ca2+ and Na+ channels in
      addition to activating a nonspecific transmembrane cation conductance. Chronic
      MeHg exposure results in ultrastructural changes and accumulation of MeHg within
      mitochondria. In vitro, MeHg inhibits several mitochondrial enzymes and
      depolarizes the mitochondria membrane subsequently reducing ATP production and
      Ca2+ buffering capacity. Inhibition of protein synthesis is observed after in
      vivo or in vitro exposures of MeHg and may be an early effect of MeHg. Thus, the
      early cellular effects of exposure to MeHg are diverse and cell damage likely
      occurs by more than one mechanism, the effects of which may be additive or
      synergistic.

PMID- 7516299
TI  - Chlordecone pretreatment alters [14C]chlordecone and [14C]cholesterol transport
      kinetics in the perfused rat liver.
AB  - Previous work demonstrated that pretreatment of mice with low doses of the
      organochlorine insecticide chlordecone (CD) altered the tissue disposition of a
      subsequent [14C]CD or [14C]cholesterol challenge dose. The profile of these
      changes was consistent with the induction of a protein integral to hepatic
      CD/cholesterol turnover. The present study was undertaken to confirm similar in
      vivo effects in the rat and to analyze potential CD-induced changes in hepatic
      transport kinetics in the perfused rat liver. For in vivo experiments, male,
      Sprague-Dawley rats were treated with CD (5, 15, or 40 mg/kg) and challenged 3 or
      7 days later with a 5 mg/kg [14C]CD tracer dose. Rats challenged 3 days after
      treatment and evaluated 16 hr later showed a dose-dependent decrease in hepatic
      [14C]CD relative to controls. This decrease could not be attributed to
      alterations in liver mass or total liver lipid. For kinetics studies, rats
      received 15 mg/kg CD and livers were perfused 3 days later. Following a brief (5
      7 min) single-pass perfusion, the perfusate was replaced with recirculating
      buffer containing albumin-bound [3H]oleic acid or high-density lipoprotein-bound
      [14C]CD or [14C]cholesterol. Livers from pretreated animals had significantly
      decreased rates of [14C]CD and [14C]cholesterol uptake. Efflux of [14C]CD and
      biliary excretion of [14C]cholesterol were increased. No changes were observed in
      uptake or biliary excretion of [3H]oleic acid. SDS-PAGE of hepatic cytosol
      revealed an enhanced band intensity corresponding to a M(r) of 25,600 in livers
      from pretreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516302
TI  - Expression of manganese superoxide dismutase promotes cellular differentiation.
AB  - Manganese superoxide dismutase (MnSOD) is a nuclear encoded mitochondrial matrix
      enzyme that scavenges toxic superoxide radicals. It has been shown that increased
      generation of reactive oxygen species is associated with the differentiation of
      microorganisms. To test the hypothesis that the ability of mitochondrial
      superoxide dismutase to neutralize a cellular hyperoxidant state is important for
      differentiation of mammalian cells, we examined the effect of transfection of
      MnSOD into mouse embryo fibroblasts on cellular differentiation. C3H10T1/2 cells
      served as a model for differentiation because these cells can be triggered to
      differentiate into myoblasts, adipocytes, and chondrocytes by treatment with 5
      azacytidine. In this report, myoblast differentiation was defined by the presence
      of multinucleated cells, appearance of Z-bands, and expression of actin and
      desmin in the differentiated cells. Transfection of MnSOD gene was found to
      greatly enhance differentiation of C3H10T1/2 cells into myoblasts by 5
      azacytidine. This result identifies MnSOD as an important factor for cell
      differentiation and supports a role for reactive oxygen species in the process of
      cellular differentiation.

PMID- 7516301
TI  - The Drosophila maternal effect locus deadhead encodes a thioredoxin homolog
      required for female meiosis and early embryonic development.
AB  - This study describes the identification, function and molecular characterization
      of deadhead, a Drosophila thioredoxin homolog. Although in vitro studies have
      shown that thioredoxin can post-translationally regulate the activity of many
      different proteins, we find that this homolog is not essential for viability. The
      phenotypic analysis of two different mutations which eliminate function suggests
      that dhd is essential for female meiosis. The majority of eggs laid by females
      homozygous for null mutations are fertilized but fail to complete meiosis. A
      small number of escaper embryos initiate development and display a range of
      phenotypes suggesting functions in both preblastoderm mitosis and head
      development. Our analysis of deadhead's RNA expression pattern is consistent with
      its maternal effect function: the RNA is predominately expressed in the nurse
      cells of the ovary, is maternally deposited into the egg, but does not appear to
      be zygotically expressed during embryogenesis. Thus both our genetic and
      molecular data are consistent with a function during meiosis and preblastoderm
      mitosis. Whether the head defect indicates an additional function or is an
      indirect consequence of earlier defects remains to be determined.

PMID- 7516304
TI  - Keratin 9 gene mutational heterogeneity in patients with epidermolytic
      palmoplantar keratoderma.
AB  - Mutations in the human keratin 9 gene have recently been shown to be involved in
      the etiology of palmoplantar keratoderma (PPK). We have investigated eleven
      unrelated German kindreds with the epidermolytic variant of PPK (EPPK) for
      mutations in the keratin 9 gene. We have identified two novel mutations, M156V
      and Q171P, both in the coil 1A segment of keratin 9. Mutation M156V was detected
      in two unrelated patients with EPPK, and mutation Q171P was shown to cosegregate
      with the disease in a large four-generation family. These findings confirm the
      functional importance of coil 1A integrity for heterodimerisation in keratins and
      for intermediate filament assembly. Our results provide further evidence for
      mutational heterogeneity in EPPK, and for the involvement of keratins in diseases
      of hyperkeratinisation and epidermolysis.

PMID- 7516307
TI  - Northwestern lab may change future of dental education.

PMID- 7516305
TI  - Identification of three novel mutations (457 TAT-->G, D192G, Q685X) in the
      Slovenian CF patients.
AB  - Chromosomes from a cohort of 60 Slovenian families, corresponding to the 121
      cystic fibrosis (CF) chromosomes available, were fully scanned for mutations in
      the coding sequence of the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene (The 60 families yielded 121 CF alleles because the mother of one
      patient was also affected). This corresponds to the 27 exons and intron/exon
      boundaries that have been studied in chromosomes carrying unidentified alleles.
      As a result of this survey 84% of the alleles are now clearly identified and we
      describe in this paper three novel mutations (457 TAT-->G, D192G, and Q685X).

PMID- 7516306
TI  - Affected sib-pair analysis of the GLUT1 glucose transporter gene locus in non
      insulin-dependent diabetes mellitus (NIDDM): evidence for no linkage.
AB  - Despite the strong evidence for a major role played by genetic factors in the
      aetiology of non-insulin-dependent diabetes mellitus (NIDDM), the genes involved
      are still unknown. Association studies of candidate genes for the inheritance of
      NIDDM have so far yielded inconclusive results. Some evidence exists for an
      association between NIDDM and the glucose transporter gene GLUT1, involved in
      basal glucose transport, although this has not been confirmed. In the present
      study we have tested the hypothesis of linkage between NIDDM and the GLUT1 gene,
      using affected sib-pairs. With this method the concordance observed for a given
      gene marker is compared with that expected under the assumption of no linkage
      between that marker and the disease. Fifty-four pedigrees (22 Italians and 32
      British), for a total of 82 sib-pairs were studied by the affected sib-pair
      method proposed by Weeks and Lange, using two restriction fragment length
      polymorphisms (RFLPs) at the GLUT1 locus, the MspI RFLP, at an estimated 0.171
      recombination frequency from the GLUT1 gene, and the XbaI RFLP, located within
      the GLUT1 gene and previously shown to be associated with the disease. Results
      showed that the MspI marker and NIDDM segregate independently; for the XbaI RFLP,
      linkage could be shown only if the results were weighted by the allele frequency
      [f(p) = 1/p], and only in the Italian and the combined (Italian and British) sib
      pair groups. Multilocus analysis with both markers was also negative. We conclude
      that the GLUT1 gene is very unlikely to play a major role in the aetiology of
      NIDDM, although an accessory role cannot be excluded, and studies of the gene
      sequence should help to clarify this question.

PMID- 7516303
TI  - Properties of cardiac I(leak) induced by photosensitizer-generated reactive
      oxygen.
AB  - We reported previously that photomodification of single frog cardiac cells by
      Rose Bengal induces a time-independent current, designated I(leak)++, having a
      linear current-voltage (I/V) relationship. The purpose of the present study is to
      better characterize the properties of I(leak)++. Initially, I(leak)++ has a
      reversal potential (ER) near -70 mV, but with time, ER shifts toward a final
      value near 0 mV. This shift in ER is accompanied by a marked increase in
      conductance (slope of I/V relationship). Evidence is presented that the
      depolarizing shift in ER with time during photomodification results from a loss
      of membrane selectivity allowing sodium to make an increasing contribution to
      I(leak)++. Potassium also contributes to I(leak)++, as indicated by marked
      depolarizing shifts in ER following replacement of intracellular potassium with
      either cesium or tetraethylammonium. Since these results occur in calcium-free
      external media, the depolarizing shifts in ER and increased conductance are not
      related to activation of a calcium-dependent nonselective cation channel.
      However, I(leak) does have some properties similar to nonselective cation
      currents recently reported to be activated by membrane breakdown products such as
      arachidonic acid and lysophosphoglycerides.

PMID- 7516308
TI  - Is asparagine-linked protein glycosylation an obligatory requirement for
      angiogenesis?
AB  - Dependence of protein N-glycosylation on capillary endothelial cell proliferation
      has been studied. Amphomycin, a potent N-glycosylation inhibitor, inhibited
      capillary endothelial cell proliferation in a dose-dependent manner. beta-Agonist
      isoproterenol as well as other intracellular cAMP enhancing agents, viz. cholera
      toxin, prostaglandin E1 and 8Br-cAMP, also enhanced capillary endothelial cell
      proliferation. In addition to cell proliferation, isoproterenol also enhanced
      protein glycosylation in these cells. Isoproterenol effect was mediated by beta
      adrenoreceptors, as it got reduced on pre-treatment of cells with either atenolol
      or ICI 118, 551 or propranolol. Furthermore, isoproterenol stimulation of protein
      glycosylation by exogenous dolichyl monophosphate and its inhibition by
      tunicamycin (GlcNAc-1P transferase inhibitor) supported the concept that
      isoproterenol specifically stimulated protein N-glycosylation event(s) in the
      cell.

PMID- 7516310
TI  - Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and
      interleukin-6 by human monocytes.
AB  - Purified cell walls representing a wide variety in teichoic acid and
      peptidoglycan structure prepared from eight different gram-positive bacterial
      species induced the production of tumor necrosis factor alpha (TNF-alpha) and
      interleukin-6 from human monocytes in the presence of 10% plasma or serum.
      Significant amounts of cytokines began to be produced at concentrations above 100
      ng to 1 microgram of cell walls per ml, with maximal production requiring 10 to
      100 micrograms of cell wall material per ml. In the absence of plasma, the
      cytokine-inducing capacity of cell wall preparations was lower by at least an
      order of magnitude. The serum-derived cofactor was inactivated by heating at 90
      degrees C for 30 min, suggesting that the activity is associated with a protein.
      On the other hand, replacement of normal with hypogammaglobulinemic plasma,
      inactivation of complement (at 56 degrees C), and blockade by the monoclonal
      antibody MY4 of the CD14 receptors on monocytes did not inhibit the production of
      TNF-alpha induced by whole cell walls. Cell walls also stimulated production of
      TNF-alpha induced by whole cell walls. Cell walls also stimulated production of
      TNF-alpha in the presence of polymyxin B, and macrophages derived from the
      lipopolysaccharide-insensitive cell line of C3He/HeJ mice also produced this
      cytokine when stimulated by cell walls. Both peptidoglycan and the soluble glycan
      teichoic acid component prepared by an enzymatic method from the same wall
      preparation exhibited a serum-dependent induction of TNF-alpha from monocytes,
      while stem peptides and disacharride peptides had only poor, if any, activity.
      Cell walls may contribute to the septic shock induced by gram-positive bacteria.

PMID- 7516309
TI  - Soluble intercellular adhesion molecules in human schistosomiasis: correlations
      with disease severity and decreased responsiveness to egg antigens.
AB  - Granuloma formation, the principal pathologic consequence of infection with
      Schistosoma mansoni, is a complex process involving intricate cell-cell
      interactions in which intercellular adhesion molecules are likely to participate.
      To examine this possibility, sera of schistosomiasis patients in various clinical
      groups were assayed for the presence of soluble intercellular adhesion molecule 1
      (sICAM-1) and soluble E-selectin (sE-selectin). Comparisons were made between
      groups with different infection intensities (as predicted by fecal egg count) as
      well as between groups with severe (hepatosplenic) or milder (intestinal)
      pathology. All groups had elevated levels of sICAM-1 compared with controls.
      Also, patients in the high egg-excreting and hepatosplenic groups had
      significantly higher levels of serum sICAM-1 than patients in the low-egg
      excreting and intestinal groups, respectively. The levels of sE-selectin were
      significantly elevated in the sera of all patients except those in the
      hepatosplenic group compared with controls. Patients in the intestinal group had
      significantly higher levels of sE-selectin in their sera than did hepatosplenic
      group patients, but serum sE-selectin levels of high- and low-egg-excreting
      patients were comparable. A striking finding of this study was the inverse
      correlation observed between sICAM-1 levels and peripheral blood mononuclear cell
      responses to schistosome soluble egg antigens (SEA) but not with responses to
      other schistosome antigens, purified protein derivative, or mitogen. Because ICAM
      1 can perform a costimulatory function in antigen-presenting cell-T cell
      interactions, it is possible that shedding of ICAM-1 in the granuloma
      microenvironment interrupts proper costimulation, leading to unresponsive SEA
      specific T cells. In this way, sICAM-1 could be one factor contributing to the
      observed modulation of cellular responses to SEA in chronic human
      schistosomiasis.

PMID- 7516311
TI  - Gamma interferon induces rapid and coordinate activation of mitogen-activated
      protein kinase (extracellular signal-regulated kinase) and calcium-independent
      protein kinase C in human monocytes.
AB  - Gamma interferon plays an important role in regulating the functional properties
      of mononuclear phagocytes. In the present study, the role of activated protein
      kinases in the mechanism of action of gamma interferon cell signaling in human
      peripheral blood monocytes was investigated. Analysis in vitro of 100,000 x g
      cytosolic fractions from untreated and interferon-treated cells showed that
      agonist treatment resulted in time- and concentration-dependent increases in
      phosphotransferase activity when myelin basic protein (MBP) was used as the
      substrate. Anion-exchange chromatography of high-speed supernatants prepared from
      detergent extracts of interferon-treated cells revealed two discrete peaks of MBP
      phosphotransferase activity. Immunoblotting of fractions from these peaks with
      antiphosphotyrosine antibodies and with antibodies that specifically recognize
      the family of mitogen-activated protein (MAP) kinases detected a MAP kinase with
      a subunit M(r) of 42,000 in the earliest-eluting peak (peak 1). Phosphorylation
      of the 42,000-M(r) protein on tyrosine was observed only after treatment of cells
      with interferon. The contribution of MAP kinase to the interferon-stimulated
      activity in peak 1 was confirmed by quantitative immunoprecipitation with anti
      MAP kinase and antiphosphotyrosine antibodies. The conclusion that the interferon
      activated MBP kinase in peak 1 could be accounted for by an activated MAP kinase
      was also supported by the finding that fractions from Mono Q peak 1 demonstrated
      activity towards a MAP kinase-specific substrate. The later-eluting peak of
      interferon-activated MBP phosphotransferase activity appeared to be accounted for
      by an activated protein kinase C (PKC). This conclusion is based upon analyses of
      immunoblotting and immunoprecipitation experiments with antibodies to PKC and was
      also supported by the observed inhibition of this kinase with a PKC
      pseudosubstrate peptide. The interferon-stimulated PKC present in Mono Q peak 2
      was active in the absence of calcium ions, suggesting that it is a calcium
      independent isoform of PKC.

PMID- 7516313
TI  - Tn916-generated, lipooligosaccharide mutants of Neisseria meningitidis and
      Neisseria gonorrhoeae.
AB  - A library of Tn916-generated, tetracycline-resistant (Tc) mutants of the group B
      Neisseri meningitidis strain NMB was screened by using monoclonal antibodies
      (MAbs) that recognize structural differences in neisserial lipooligosaccharide
      (LOS). The LOS of parental strain NMB had a relative molecular mass of 4.5 kDa,
      reacted with MAbs 3F11 and 6B4 but not with MAb 4C4 or 6E4, and contained a lacto
      N-neotetrose unit. Two phenotypically stable mutants, SS3 and R6, altered in LOS,
      were identified by colony immunoblots, electrophoresis, and Western immunoblots.
      The LOS of mutant SS3 was 3.4 kDa and reacted with MAbs 4C4 and 6E4 but not MAb
      3E11 or 6B4. The LOS of mutant R6 was 3.1 to 3.2 kDa and reacted with MAb 6E4 but
      not MAb 3F11, 6B4, or 4C4. Thus, the LOSs of the R6 and SS3 mutants were
      predicted to contain different truncations of the core oligosaccharide. The LOS
      phenotype of each mutant was linked to Tc(r), as determined by transformation of
      the parent strain with DNA from the mutant. Southern hybridizations and single
      specific-primer PCR revealed in each mutant a single truncated tn916 insertion
      which had lost genes required for mobilization. Tn916 mutagenesis was used to
      identify two distinct genetic sites in the meningococcal chromosome involved in
      biosynthesis of the oligosaccharide chain of LOS and to create genetically
      defined LOS mutants of N. meningitidis and Neisseria gonorrhoeae.

PMID- 7516312
TI  - Neutralizing monoclonal antibodies to an extracellular Pseudomonas cepacia
      protease.
AB  - Pseudomonas cepacia produces at least two extracellular proteases with apparent
      molecular masses of 36,000 and 40,000 Da. The 36-kDa protease has high
      proteolytic activity and the 40-kDa protease has low proteolytic activity with
      hide powder azure as a substrate. Monoclonal antibodies (MAbs) were raised
      against the purified 36- and 40-kDa proteases. Several MAbs directed against the
      36-kDa protease were found to recognize the 40-kDa protease by Western immunoblot
      analysis. Similarly, a MAb directed against the 40-kDa protease recognized the 36
      kDa protease, suggesting that these two proteases may be immunologically related.
      A MAb directed against the 36-kDa protease, designated 36-6-8, and a MAb directed
      against the 40-kDa protease (MAb G-11) cross-reacted with other extracellular
      proteases, such as Pseudomonas aeruginosa elastase and alkaline protease,
      Pseudomonas pseudomallei protease, and the Vibrio cholerae
      hemagglutinin/protease. MAb 36-6-8 neutralized the P. cepacia 36-kDa protease, P.
      aeruginosa elastase, P. pseudomallei protease, and V. cholerae
      hemagglutinin/protease but did not affect P. aeruginosa alkaline protease
      activity. In contrast, MAb G-11 to the 40-kDa protease neutralized only the P.
      cepacia 36-kDa protease. This evidence suggests that the neutralizing MAb, 36-6
      8, recognizes an epitope conserved among some metalloproteases. This epitope may
      lie at or near the active site of the P. cepacia 36-kDa protease and P.
      aeruginosa elastase.

PMID- 7516316
TI  - Symbolic representation and the components of a group-as-a-whole model.
AB  - As participants engage in the group psychotherapy process, they often generate
      figurative forms (i.e., metaphoric images) representative of their experiences
      together. Metaphors function as symbols when they depict important information
      about the group-as-a-whole, as well as about the individuals that comprise it.
      Symbols are cultural phenomena that express, contain, and transform the group
      process. This article presents a model of how metaphoric and symbolic images
      arise spontaneously as organizational phenomena and how they might be elaborated
      therapeutically. A bridge is made between individualistic and group-as-a-whole
      perspectives on the group process by demonstrating how members come together
      through the evolution of shaping circumstances, bipolar themes, talking points,
      particularizations of experience, and organizing images.

PMID- 7516314
TI  - G(AnH)MTetra, a naturally occurring 1,6-anhydro muramyl dipeptide, induces
      granulocyte colony-stimulating factor expression in human monocytes: a molecular
      analysis.
AB  - N-Acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-isoglutam yl-m-
      diaminopimelyl-D-alanine [G (Anh)MTetra], a naturally occurring breakdown product
      of peptidoglycan from bacterial cell walls, was studied for its ability to induce
      granulocyte colony-stimulating factor (G-CSF) mRNA and protein expression in
      human adherent monocytes. Resting monocytes did not express G-CSF mRNA or secrete
      G-CSF protein. In contrast, monocytes exposed to G(Anh)MTetra showed a dose
      dependent increase in G-CSF mRNA accumulation, which correlates with the
      secretion of G-CSF protein. Maximal levels of G-CSF mRNA were reached within 2 h
      of activation. Expression of G-CSF was mediated by an increase in the stability
      of G-CSF transcripts rather than by an increase in the transcription rate of the
      G-CSF gene. Experiments with the protein synthesis inhibitor cycloheximide
      revealed that G(Anh)MTetra-induced G-CSF mRNA expression was independent of new
      protein synthesis. Furthermore, it was shown that the effect of G(Anh)MTetra was
      regulated by a protein kinase C-dependent pathway, whereas protein kinase A and
      tyrosine kinases were not involved. Finally, it was shown that G(Anh)MTetra also
      induced G-CSF mRNA expression in human endothelial cells. The data indicate that,
      besides lipopolysaccharide, other naturally occurring bacterial cell wall
      components are able to induce G-CSF expression in different hematopoietic cells.

PMID- 7516315
TI  - Epitope specificity and isoforms of the mycobacterial 19-kilodalton antigen.
AB  - The topography and specificity of B- and T-cell stimulatory epitopes from the 19
      kDa protein of Mycobacterium tuberculosis were investigated by using overlapping
      synthetic peptides. Murine antisera identified two cryptic epitopes (residues 11
      to 30 and 61 to 80) and one species-specific immunodominant epitope (residues 140
      to 159). Immunoglobulins G1 and G2a antibody isotypes varied for the respective
      peptide immunogens but without relationship to the T-cell cytokine profiles which
      were characterized by high gamma interferon and low interleukin 5 levels.
      Antisera to recombinant M. tuberculosis 19-kDa protein (rGST-19) cross-reacted
      with homologous proteins of similar size from organisms of the Mycobacterium
      avium-intracellulare complex. Two-dimensional gel electrophoresis revealed
      differences in the number, relative mobility, and charge of isoforms of the 19
      kDa protein, possibly reflecting posttranslational modifications. The
      immunodominant T-cell epitope from the M. tuberculosis 19-kDa protein (residues
      61 to 80) and the corresponding peptide sequence from Mycobacterium avium subsp.
      intracellulare (residues 64 to 83), differing at five residues, were both
      recognized in a genetically permissive manner. Peptides 61-80 and 64-83
      stimulated cross-reactive responses in BALB/c (H-2d) mice, while in the C57BL/10
      (H-2b) strain, responses to peptide 61-80 were species specific. In purified
      protein derivative-positive healthy individuals, the M. avium subsp.
      intracellulare peptide stimulated stronger responses than did the M. tuberculosis
      peptide, whereas patients with active tuberculosis had enhanced in vitro T-cell
      responses to both peptides.

PMID- 7516317
TI  - Androgen receptor expression in the cervix of androgen-treated female-to-male
      transsexuals: association with morphology and chain-specific keratin expression.
AB  - Long-term androgen treatment of female-to-male transsexuals is associated with
      morphological changes of the ectocervical epithelium. This study was designed to
      correlate the histological changes of the ectocervix to modulation of androgen
      receptor (AR) and keratin expression. We evaluated AR expression by
      immunohistochemistry using monoclonal antibody F39.4 specific for the N-terminal
      domain of the human AR. In the cervix of five of six transsexuals, the epithelium
      of the ectocervix displayed areas of increased cellularity lacking complete
      maturation into flattened squamous epithelial cells. This morphological change
      was associated with the acquisition of keratins 8 and 19 by all cell layers. In
      the normal ectocervix, these keratins are characteristic of the basal cell layer.
      The morphologically altered ectocervix of transsexuals displayed an intense AR
      expression in all cell layers, which contrasts with the selective, faint nuclear
      staining of the basal cells of the ectocervix of both premenopausal and
      postmenopausal women. Additionally, long-term androgen treatment led to
      consistently increased AR expression by the stromal cells of the endocervix and
      ectocervix. Our data imply that the morphological changes in the transsexual
      ectocervix reflect an androgen-mediated arrest of maturation. The observed
      increase in AR expression by the stromal cells of the ectocervix of androgen
      treated transsexual females provides an example of androgen-mediated upregulation
      of AR expression in human tissues.

PMID- 7516318
TI  - Binding of enkephalin/dextran conjugates to opioid receptors.
AB  - [ala2]Enkephalin molecules were connected to dextran, and the affinities of the
      enkephalin/dextran conjugates for opioid receptors were studied. Two kinds of
      enkephalin derivatives, YaGFLGK-NH2 and YaGFLGS'S'PS'S'PS'KP-OMe (S' represents a
      Sar residue) were prepared. They retained the high affinity of the enkephalin
      unit toward opioid receptors. On the other hand, receptor affinity of the
      enkephalin derivative/dextran conjugates became lower than that of the enkephalin
      derivatives. Fluorescence from the Tyr residue of the conjugates in a buffer
      solution was less quenched by succinimide than that of the enkephalin
      derivatives. Therefore, in these conjugates, the binding of the enkephalin
      moieties to receptors should be hindered by a steric effect of the dextran
      matrix. However, the receptor affinity (as defined on the basis of an enkephalin
      unit) increased on increasing the amount of enkephalin units connected to the
      dextran matrix, especially in the case of the connection through a shorter spacer
      arm, suggesting simultaneous binding to a few receptors by the conjugate.

PMID- 7516319
TI  - Modification of metabolism of transplantable and spontaneous murine tumors by the
      nitric oxide synthase inhibitor, nitro-L-arginine.
AB  - PURPOSE: To determine the effects of the nitric oxide synthase inhibitor, nitro-L
      arginine on energy metabolism in transplantable and spontaneous murine tumors.
      METHODS AND MATERIALS: The responses of the transplantable murine tumor SCCVII/Ha
      and a range of spontaneously arising murine mammary adenocarcinomas to 10 mg/kg
      IV nitro-L-arginine were examined using in vivo 31P magnetic resonance
      spectroscopy (MRS). The influence of Hypnorm/Hypnovel anesthesia on the response
      to nitro-L-arginine was also determined in the SCCVII/Ha tumors. Data were
      expressed as changes in the inorganic phosphate peak area relative to the sum of
      all peak areas from the 31P MR spectrum, or Pi/total. RESULTS: Nitro-L-arginine
      at 10 mg/kg IV increased Pi/total 2-3-fold in the SCCVII/Ha tumors for at least 2
      h after administration, in both anesthetized and nonanesthetized mice, consistent
      with increased tumor hypoxia. Similar increases in Pi/total were observed after
      10 mg/kg IV nitro-L-arginine in 13 spontaneous murine tumors from three different
      mouse strains, where anesthetic was used. CONCLUSION: The results indicate that
      tumor metabolism may be modified by an inhibitor of nitric oxide synthesis, that
      this modification occurs in both transplantable and spontaneous murine tumors and
      is not affected by anesthetic.

PMID- 7516320
TI  - Comparative studies of UV-induced DNA cleavage by structural isomers of an
      iodinated DNA ligand.
AB  - PURPOSE: To evaluate the importance of the position of the halogen atom in
      iodinated DNA-binding bibenzimidazoles, with respect to sensitization of UV-A
      induced DNA breakage. METHODS AND MATERIALS: Three analogues of iodoHoechst
      33258, denoted ortho-, meta- and paraiodoHoechst, according to the site of iodine
      substitution, were synthesized. Plasmid DNA (pBR322) was used to assay UV-A
      induced DNA single-strand breaks (ssbs). The location of the sites of strand
      breakage was determined by DNA sequencing gel analysis, using a 32P-endlabelled
      oligoDNA with a single binding site for the ligands. RESULTS: A clear trend in
      decreasing activity of sensitization of UV-induced DNA ssbs was established:
      ortho- > meta-, para- > iodoHoechst 33258. The sequencing gel studies showed that
      orthoiodoHoechst was distinct from the other three compounds, with respect to the
      sites of DNA strand breakage and the chemistry of the cleavage reaction.
      CONCLUSION: The position of iodine substitution in iodinated bibenzimidazoles
      determines the location of the carbon-centered radical on the ligand in the minor
      groove of DNA. DNA strand cleavage is mediated by abstraction of a nearby
      deoxyribosyl H-atom. Hence, the position of the radical species determines: which
      deoxyribosyl group is attacked (i.e., site of cleavage relative to the ligand
      binding site); which H-atom is abstracted, more specifically which of the five
      deoxyribosyl carbons is involved (i.e., the chemistry of the cleavage reaction),
      and the stereochemistry of the transition state for the H-atom abstraction (and
      hence the efficiency or extent of strand breakage). The ortho-compound represents
      the best example to date of iodinated DNA ligands designed as potential radiation
      sensitizers, as an extension of the well-established sensitization by halogenated
      DNA precursors.

PMID- 7516321
TI  - Phase II trial of external beam radiation with etanidazole (SR 2508) for the
      treatment of locally advanced prostate cancer.
AB  - PURPOSE: To evaluate the efficacy and toxicity of the addition of etanidazole
      (ETA) to external beam radiation. METHODS AND MATERIALS: Fifty eight previously
      untreated patients with locally advanced adenocarcinoma of the prostate were
      entered on a Phase II trial of etanidazole (ETA) combined with standard external
      beam radiation therapy. ETA was given concurrently with irradiation. Four
      patients received less than 25% of the intended dose of ETA and were ineligible
      for further analysis. The stage of the remaining patients were T2c-11, T3-39, T4
      1, bulky local recurrence after prostatectomy-1, and T3, N1-2. RESULTS: Forty
      five of 54 patients (83.3%) achieved a clinical complete response (CCR) in the
      prostate and seminal vesicles as judged by digital rectal exam (DRE). Responses
      were rapid with a median time to CCR of 3.4 months, range 0-22.8 months. Local
      control was maintained in 82% of the patients who achieved a CCR. Fifteen of 32
      eligible patients with a normal DRE underwent prostate biopsies from 12-20 months
      after treatment, seven had negative biopsies (46.6%). Distant metastases occurred
      in 18 patients (33.3%). Pretreatment prostatic specific antigen (PSA), Gleason
      score, and stage were not associated with treatment outcome in a univariate
      analysis. CONCLUSION: While ETA plus radiation was associated with a rapid CCR,
      the overall treatment outcome of these patients appeared to be similar to
      published reports of patients receiving RT alone. The rapid response rate may
      imply biologic activity of the ETA. In future trials, it may be reasonable to
      focus on patients at lower risk for the subsequent development of distant
      disease.

PMID- 7516322
TI  - Contribution of potassium channels to active hyperemia of the canine diaphragm.
AB  - Glibenclamide, iberiotoxin, and apamin (blockers of ATP-sensitive, large
      conductance, and small-conductance Ca(2+)-activated K+ channels, respectively)
      were infused into the diaphragmatic vasculature of anesthetized indomethacin
      treated dogs to assess the contribution of K+ channels to active hyperemia.
      Diaphragmatic blood flow (Qphr) and O2 uptake (VO2di) were measured at rest and
      during 2 min of continuous left phrenic nerve stimulation at 0.5, 1, 2, and 4 Hz.
      These measurements were repeated before (control) and after the infusion of a
      selective K+ channel blocker in three groups of animals. Glibenclamide at 10(-5)
      M significantly attenuated Qphr at rest and in response to all stimulation
      frequencies. Whereas resting VO2di remained unchanged, glibenclamide infusion
      significantly reduced VO2di in response to all stimulation frequencies. The slope
      of the linear relationship between Qphr and VO2di, however, was not affected by
      glibenclamide. By comparison, infusion of iberiotoxin (10(-7) M) in a second
      group reduced Qphr at rest and in response to 0.5- and 1-Hz stimulation, whereas
      Qphr measured in response to 2- and 4-Hz stimulation remained similar to control
      values. Apamin (10(-6) M) infusion in a third group reduced only resting Qphr
      with no effect on active hyperemia during phrenic nerve stimulation. Neither
      iberiotoxin nor apamin influenced resting or stimulated VO2di. In all groups
      diaphragmatic tension measured after the infusion of K+ channel blockers remained
      similar to control values. These results indicate that K+ channels, especially
      those sensitive to glibenclamide, modulate the increase in Qphr and VO2di in
      response to moderate augmentation of metabolic demands.

PMID- 7516324
TI  - The Arkansas Cancer Pain Initiative.

PMID- 7516326
TI  - Transrectal fine needle aspiration of prostate.
AB  - 56 patients with prostatic enlargement were subjected to transrectal fine needle
      aspiration (FNA) of prostate. The cytologic diagnosis was correlated with
      histology in 55 cases. Benign prostatic hyperplasia (BPH) was diagnosed in 44
      cases. In 18 of these, there was associated chronic prostatitis in three cases
      acute prostatitis and in two cases granulomatous prostatitis. One case of
      tuberculous prostatitis and 11 cases of prostatic carcinoma could also be
      diagnosed on cytologic basis. There was only one false negative and no false
      positive cytodiagnosis was made.

PMID- 7516325
TI  - A case of barium carbonate poisoning.

PMID- 7516323
TI  - Canine hindlimb blood flow and O2 uptake after inhibition of EDRF/NO synthesis.
AB  - The nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester
      (L-NAME) was used to determine whether the decrease in canine hindlimb blood flow
      (QL) with NOS inhibition would limit skeletal muscle O2 uptake (VO2). Arterial
      inflow and venous outflow from the hindlimb were isolated, and the paw was
      excluded from the circulation. Pump perfusion from the right femoral artery kept
      the hindlimb perfusion pressure near the auto-perfused level. Six anesthetized
      dogs received L-NAME (20 mg/kg i.v.), whereas another group of five dogs received
      the stereospecific enantiomer N omega-nitro-D-arginine methyl ester (D-NAME 20
      mg/kg i.v.). Efficacy of NOS inhibition was tested with intra-arterial boluses of
      acetylcholine. QL was measured continuously, and whole body and hindlimb VO2 were
      measured 60 and 120 min after L-NAME or D-NAME. Whole body VO2 remained at
      control levels, but cardiac output decreased from 117 +/- 17 to 57 +/- 7 ml.kg
      1.min-1 60 min after L-NAME (P < 0.05) and remained at that level for the
      duration of the experiment. Cardiac output was significantly higher in the D-NAME
      group than in the L-NAME group at 60 min. After L-NAME, QL fell 24% but VO2
      increased from 5.2 +/- 0.4 to 7.4 +/- 0.6 ml.kg-1.min-1 (P < 0.05). No change in
      QL or VO2 occurred after D-NAME. NOS inhibition did not limit hindlimb VO2,
      despite decreases in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516327
TI  - A cleavable N-terminal signal peptide is not a prerequisite for the biosynthesis
      of glycosylphosphatidylinositol-anchored proteins.
AB  - During the biosynthesis of glycosylphosphatidylinositol (GPI)-anchored proteins,
      an N-terminal signal peptide is used to direct biosynthesis to the endoplasmic
      reticulum. It was previously unknown whether or not this signal must be removed
      during the biosynthesis of GPI-anchored proteins. Using neutral endopeptidase (EC
      3.4.24.11), a well characterized type II membrane protein that is attached to the
      membrane via an uncleaved N-terminal signal peptide, we extended its C terminus
      with 33 of the 37 amino acids of the GPI anchor signal sequence of decay
      accelerating factor. When expressed in COS-1 and Chinese hamster fibroblast (CHW)
      cells, the protein was shown to possess both transmembrane and GPI anchors,
      indicating that a cleavable N-terminal signal peptide is not a prerequisite for
      the biosynthesis of GPI-anchored proteins.

PMID- 7516328
TI  - Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B
      with predominance of p50 homodimers.
AB  - Stimulation of the human monocytic cell line Mono Mac 6 with lipopolysaccharide
      (LPS) leads to rapid and transient expression of cytokines like tumor necrosis
      factor (TNF). When such cells are precultured for 2 days with a low dose of LPS
      (20 ng/ml) followed by stimulation with a high dose of LPS (1 microgram/ml),
      expression of the TNF gene is minimal, i.e. the cells are tolerant. In nuclear
      run-on analysis, such tolerant cells show only a low degree of transcription,
      indicating that tolerance operates at or upstream of the transcription level. The
      CD14 LPS receptor is, however, up-regulated (not down-regulated) in tolerant
      cells, and LPS can, in fact, still lead to activation of tolerant cells as
      evidenced by mobilization of the transcription factor nuclear factor kappa B (NF
      kappa B). Resolution of the NF-kappa B complex in gel shift analysis shows that
      the binding protein, mobilized in naive Mono Mac 6 cells, consists mainly of p50
      p65 heterodimers, while in tolerant cells, the p50 homodimer is predominant. This
      increase in p50 homodimers coincides with an increase in p105 mRNA, suggestive of
      a transcriptional up-regulation of p50. Reporter gene analysis reveals that the
      NF-kappa B complex mobilized in tolerant cells is functionally inactive in that
      NF-kappa B-dependent luciferase constructs containing the human immunodeficiency
      virus long terminal repeat or the TNF 5'-region show only minimal transactivation
      after LPS stimulation. Similar to Mono Mac 6 cells, primary blood monocytes, when
      precultured with a low dose of LPS, also become tolerant and produce little TNF
      after LPS stimulation. The tolerant blood monocytes also up-regulate CD14, and
      they mobilize NF-kappa B with a predominance of p50 homodimers. Taken together,
      these results demonstrate that tolerance to LPS is determined by post-receptor
      mechanisms that involve an altered composition of the NF-kappa B complex.

PMID- 7516329
TI  - Regulation of fibrinolytic activity of neutrophil leukocyte elastase, plasmin,
      and miniplasmin by plasma protease inhibitors.
AB  - The effect of solid-phase fibrin on the inactivation of plasmin, miniplasmin, and
      neutrophil leukocyte elastase (PMN-elastase) by plasma protease inhibitors (alpha
      2-antiplasmin, alpha 1-protease inhibitor, alpha 2-macroglobulin) was studied. In
      Hanks' balanced salt solution, fibrin reduces the second-order rate constant for
      the inhibition of PMN-elastase by alpha 1-protease inhibitor from 8,760 x 10(4)
      to 4 x 10(4) M-1.s-1 and by alpha 2-macroglobulin from 121 x 10(4) to 1.8 x 10(4)
      M-1.s-1. The rate constant for miniplasmin inactivation by alpha 2-antiplasmin
      decreases from 99 x 10(4) to 1 x 10(4) M-1.s-1, by alpha 2-macroglobulin from 78
      x 10(4) to 1.8 x 10(4) M-1.s-1, and by alpha 1-protease inhibitor from 0.11 x
      10(4) M-1.s-1 to 0. Plasmin bound to fibrin is completely protected against alpha
      2-macroglobulin and alpha 1-protease inhibitor, whereas the rate constant for the
      inactivation by its primary plasma inhibitor alpha 2-antiplasmin is reduced from
      430 x 10(4) to 1.08 x 10(4) M-1.s-1. The competition of substrate and inhibitor
      for the enzyme was also studied, using fibrin preincubated with inhibitor. Under
      our pseudo-first-order experimental conditions, fibrin completely eliminates
      those interactions, the second-order rate constant of which is 1.1 x 10(5) M-1.s
      1 or less in a system without fibrin surface.

PMID- 7516330
TI  - Internalization of fibroblast growth factor receptor is inhibited by a point
      mutation at tyrosine 766.
AB  - Binding of fibroblast growth factor (FGF) to the fibroblast growth factor
      receptor leads to autophosphorylation of the receptor on several tyrosine
      residues. Wild-type FGF receptor 1 (flg) and a mutated receptor (Y766F), in which
      an autophosphorylation site (Tyr-766) was mutated to phenylalanine, were
      expressed in rat myoblasts and in hematopoietic Ba/F3 cells. It was found that
      the point mutation at Tyr-766 resulted in a decrease in FGF receptor
      internalization, as well as a reduction in both ligand-induced FGF receptor down
      regulation and degradation. It has been shown previously that phosphorylation of
      Tyr-766 is essential for interaction with phospholipase C gamma and that the
      Y766F FGF receptor mutant is unable to stimulate phosphatidylinositol hydrolysis
      and Ca2+ release from internal stores. The results presented in this report
      indicate that Tyr-766 is also essential for cellular trafficking of FGF receptor.

PMID- 7516331
TI  - Tetanus toxin light chain cleaves a vesicle-associated membrane protein (VAMP)
      isoform 2 in rat pancreatic zymogen granules and inhibits enzyme secretion.
AB  - Pancreatic acinar cells, a model cell type for the study of exocytosis in non
      excitable cells, were used here to test the hypothesis that molecular mechanisms
      regulating exocytosis from neuronal and neuroendocrine cells may also be utilized
      in exocrine cells. Using specific antisera raised against vesicle-associated
      membrane protein (VAMP) isoforms 1 and 2, we have identified VAMP-2, but not VAMP
      1, immunoreactive proteins on rat pancreatic acinar cell secretory (zymogen)
      granules. This 18-kDa protein co-migrated with rat brain synaptic vesicle VAMP-2.
      Tetanus toxin (TeTx) light chain caused complete cleavage of this protein, which
      was prevented by the addition of EDTA. This toxin also inhibited in a dose
      dependent manner Ca(2+)-stimulated enzyme secretion by up to approximately 30% in
      streptolysin O-permeabilized acini. This effect of TeTx on secretion was
      prevented by the zinc endopeptidase inhibitor captopril or by boiling the toxin.
      Incomplete inhibition of secretion by TeTx may suggest that TeTx-insensitive or
      VAMP-2-independent mechanisms also regulate exocytosis. In support, TeTx light
      chain was without effect on Rab3AL (effector domain peptide of Rab3)-mediated
      potentiation of Ca(2+)-stimulated secretion. These results indicate that a TeTx
      sensitive VAMP-2-like protein on zymogen granules participates in Ca(2+)
      regulated pancreatic enzyme secretion and that undefined Rab3AL-activated
      mechanisms may act independently to regulate exocytosis.

PMID- 7516333
TI  - Differences in intracellular calcium signaling after activation of the thrombin
      receptor by thrombin and agonist peptide in osteoblast-like cells.
AB  - Thrombin and the thrombin receptor agonist peptide (TRAP) caused a rise in
      intracellular calcium concentration ([Ca2+]i) in the human osteoblast-like cell
      line Saos-2. Striking differences in the [Ca2+]i signals elicited by these
      agonists were revealed. In cell populations, thrombin induced a transient
      increase in [Ca2+]i while TRAP caused a biphasic [Ca2+]i response consisting of
      an initial peak and a sustained plateau phase. In individual cells, thrombin
      mainly caused a single [Ca2+]i transient while TRAP induced repetitive [Ca2+]i
      spikes. Neither tyrosine phosphorylation, cAMP-dependent phosphorylation, nor
      pertussis toxin-sensitive G proteins appeared to be involved in thrombin receptor
      [Ca2+]i signaling in this cell line. However, the sustained [Ca2+]i response
      caused by TRAP was converted into a transient, thrombin-like response by
      pretreatment with serine/threonine phosphatase inhibitors. Pretreatment with the
      phorbol ester phorbol 12-myristate 13-acetate (PMA) abrogated thrombin receptor
      [Ca2+]i signaling, and TRAP-induced Ca2+ entry was inhibited by the acute
      treatment with PMA. In contrast, Ca2+ entry stimulated by thapsigargin was not
      sensitive to agents affecting serine/threonine phosphorylation. The observation
      that thrombin and TRAP, despite being agonists for a common receptor, induce
      dissimilar [Ca2+]i responses indicates that binding of TRAP alone is insufficient
      to fully regulate the thrombin receptor in Saos-2 cells.

PMID- 7516332
TI  - Differential ligand binding specificities of recombinant CD11b/CD18 integrin I
      domain.
AB  - The alpha subunits of leukocyte CD11/CD18 integrins contain an approximately 200
      amino acid "inserted" domain (I-domain) that may be important for multivalent
      adhesive recognitions. A recombinant form of the I-domain of CD11b/CD18 was
      generated and analyzed directly for interaction with complementary integrin
      ligands. CD11b I-domain bound the activation-dependent monoclonal antibody 7E3,
      and the functionally blocking anti-CD11b monoclonal antibodies OKM9, 60.1, and
      LM2/1, but not OKM1 or M1/70. Fibrinogen or soluble intercellular adhesion
      molecule-1 associated with CD11b I-domain in a concentration-dependent manner.
      Binding of 125I-fibrinogen to recombinant CD11b I-domain was saturable, governed
      by a Kd of approximately 0.22 +/- 0.06 microM, and fully inhibited by molar
      excess of unlabeled fibrinogen, or by the P1 peptide (KY)GWTVFQKRLDGSV (IC50
      approximately 2.5-5 microM), duplicating the fibrinogen gamma chain sequence
      Gly190-Val202. In contrast, 125I-factor X binding to CD11b I-domain was only
      partially inhibited (50-60%) by a molar excess of unlabeled factor X, and
      entirely unaffected by functionally blocking anti-CD11b monoclonal antibodies or
      by factor X-derived synthetic peptidyl antagonists. We conclude that the I-domain
      of CD11b participates in qualitative mechanisms of receptor activation and
      contains the binding site(s) for the CD11b/CD18 ligands fibrinogen and
      intercellular adhesion molecule-1, while it is only minimally implicated in the
      recognition of factor X.

PMID- 7516334
TI  - Slippage synthesis at the galP2 promoter of Escherichia coli and its regulation
      by UTP concentration and cAMP.cAMP receptor protein.
AB  - An intriguing mechanism in regulating transcription initiation from the gal
      operon in Escherichia coli is described. Initiation from galP2, one of the two
      promoters of the E. coli galactose operon, is shown to be subject to promoter
      clearance control in responding to changes in UTP concentration. In vitro, RNA
      polymerase (RNAP) makes a large amount of nonproductive "stuttering" initiation
      products at the galP2 promoter at high concentrations of UTP and less of the
      stuttered products at low concentrations of UTP. Conversely, RNAP makes more
      productive initiation products at low UTP concentration than at high UTP
      concentration. The transcription factor cAMP.CRP complex which normally inhibits
      transcription from galP2 also represses the stuttering synthesis from galP2. When
      galactose is used as a sole carbon source and the internal UTP pools are adjusted
      externally, a cya mutant (in which galP2 is mainly responsible for the expression
      of the gal operon and galP1 activity is minimal) has a slower growth rate and
      lower expression of the gal operon at high UTP pools than at low UTP pools. Such
      an apparent correlation between the in vitro and in vivo results allows one to
      speculate that changes in UTP concentration can modulate the expression of the
      gal operon. The implication of a gal promoter being controlled by UTP is
      discussed.

PMID- 7516335
TI  - Multiple components of the B cell antigen receptor complex associate with the
      protein tyrosine phosphatase, CD45.
AB  - Signal transduction via the B cell antigen receptor complex is regulated by
      changes in tyrosine phosphorylation of several proteins. The equilibrium between
      tyrosine phosphorylation and dephosphorylation is regulated by the combined
      action of protein tyrosine kinase and protein tyrosine phosphatase enzymes. In
      particular, the protein tyrosine phosphatase, CD45, has been shown to play an
      essential role in signal transduction via the B cell antigen receptor. Therefore,
      experiments were performed to examine the intermolecular associations between
      CD45 and phosphotyrosine-containing proteins in the B cell to identify potential
      substrates for CD45. Based on coprecipitation experiments, CD45 was found to be
      physically associated with multiple components of the B cell antigen receptor
      complex including the MB-1/B29 heterodimer. Additionally, CD45 was selectively
      associated with the src family protein tyrosine kinase, lyn. Neither blk nor fyn
      were observed to interact with CD45 even though they have been implicated in
      antigen receptor signal transduction. This finding suggests that CD45 may
      preferentially regulate the phosphorylation of lyn and thus, its activity. In
      summary, these studies provide evidence to support the hypothesis that CD45
      regulates antigen receptor-mediated signal transduction by controlling the
      tyrosine phosphorylation of multiple components of the antigen receptor complex.

PMID- 7516336
TI  - Incorporation of Rap 1b into the platelet cytoskeleton is dependent on thrombin
      activation and extracellular calcium.
AB  - Rap 1b is a 22-kDa low molecular mass GTP-binding protein which is both a member
      of the Ras superfamily and a substrate for cAMP-dependent protein kinase.
      Recently, evidence has been presented to show that Rap 1b is incorporated into
      the detergent-extracted cytoskeleton of platelets during thrombin-induced
      activation. The aims of this study were to compare the incorporation of Rap 1b
      into the detergent-extracted cytoskeleton after activation with different
      agonists, to examine the role of extracellular calcium on the incorporation of
      Rap 1b into the cytoskeleton, to investigate the relationship between the
      association of Rap 1b and other proteins with the cytoskeleton, and to determine
      the effect of phosphorylation of Rap 1b incorporation into the cytoskeleton.
      Platelets were activated with thrombin, A23187, phorbol myristate acetate, ADP,
      epinephrine, and collagen in the presence and absence of calcium. The time
      dependence of Rap 1b incorporation into the detergent-extracted cytoskeleton was
      then measured. When platelets were activated by thrombin in the presence of
      extracellular calcium, conditions which permit aggregation, incorporation of Rap
      1b into the detergent-extracted cytoskeleton was biphasic. Approximately 20% of
      the total cellular Rap 1b incorporated into the cytoskeleton within seconds and
      was followed by a slower second phase of incorporation. In contrast, when
      platelets were activated by thrombin in the absence of calcium, conditions which
      inhibit aggregation, or by the other agents in the presence or absence of
      calcium, only the initial phase of Rap 1b incorporation into the cytoskeleton was
      measured. The incorporation of Rap 1b paralleled the incorporation of membrane
      glycoproteins (GP) IIb/IIIa and PECAM-1, but not the incorporation of pp60c-src.
      The GTPase-activating protein for Ras (Ras-GAP) did not associate with the
      detergent-extracted cytoskeleton. Two-dimensional isoelectric focusing SDS
      polyacrylamide gel electrophoresis of the total cellular and cytoskeletal Rap 1b
      showed that unphosphorylated as well as phosphorylated isoforms of Rap 1b were
      incorporated into the cytoskeleton in the same molar ratio as was present in the
      intact cell. Furthermore, the rates of incorporation of phosphorylated and
      unphosphorylated Rap 1b into the cytoskeleton were similar. These experiments
      show that Rap 1b can regulate events that take place within seconds after
      activation, such as the initial formation of the cytoskeleton, as well as longer
      term changes in the cytoskeleton that occur in response to thrombin-induced
      aggregation. Furthermore, phosphorylation could modulate the (unknown) functions
      of Rap 1b as a component of the cytoskeleton.

PMID- 7516337
TI  - The T-cell antigen receptor utilizes Lck, Raf-1, and MEK-1 for activating mitogen
      activated protein kinase. Evidence for the existence of a second protein kinase C
      dependent pathway in an Lck-negative Jurkat cell mutant.
AB  - T-cell antigen receptor (TCR) ligation of an Lck-deficient Jurkat mutant, J.CaM1,
      with anti-CD3 or anti-TCR beta monoclonal antibodies failed to induce tyrosine
      phosphorylation and activation of p42MAPK. The same stimuli activated mitogen
      activated protein (MAP) kinase in J.CaM1 cells transfected with Lck,
      demonstrating that Lck plays a critical role in MAP kinase activation. Utilizing
      immunocomplex kinase assays, we demonstrated that TCR/CD3 ligation activated a
      MAP kinase kinase kinase (Raf-1) as well as a MAP kinase kinase (MEK-1) in Jurkat
      but not in J.CaM1 cells. It was possible, however, to activate Raf-1, MEK-1, and
      p42MAPK in J.CaM1 cells during treatment with the phorbol ester phorbol 12
      myristate 13-acetate, which activates protein kinase C (PKC). This demonstrates
      the presence of a PKC-dependent pathway which functions independently from Lck in
      MAP kinase activation. Stimulation of Jurkat cells with either anti-TCR beta or
      anti-CD3 monoclonal antibody failed to induce substantial tyrosine
      phosphorylation of Shc proteins or their association with Grb2 which forms a
      complex with the guanine nucleotide exchange factor hSOS. However, the same
      stimuli induced tyrosine phosphorylation of another putative guanine nucleotide
      exchange factor, p95Vav, in Jurkat but not J.CaM1 cells. Moreover, Lck was
      reversibly co-immunoprecipitated with p95Vav, and the stoichiometry of binding
      increased in anti-CD3-treated Jurkat cells. Phorbol 12-myristate 13-acetate did
      not induce tyrosine phosphorylation of p95Vav. These data show that the TCR
      activates MAP kinase by way of a signaling cascade, which depends upon Lck, and
      may be mediated by downstream events involving PKC or p95Vav which act on Raf-1
      and MEK-1.

PMID- 7516338
TI  - Evaluation of magnetic alginate beads as a solid support for positive selection
      of CD34+ cells.
AB  - Paramagnetic alginate beads with a 10-100 microns size range have been developed.
      These beads, when activated with chloroacetic anhydride and covalently coupled to
      avidin (30 micrograms/mg beads), were able to bind biotinylated goat anti-mouse
      (B-GAM) antibody (Ab). The beads with immobilized antibody were then used as a
      model system for the capture and non-enzymatic release of CD34+ (KG1a) cells. A
      maximum of 82% KG1a (average = 65 +/- 16.1%) cell capture, and 57% (average = 51
      +/- 5.9%) cell release has been attained using this model system. Optimization of
      the system in terms of further bead size reduction, and in terms of developing a
      system to recover released cells with high purity, will make an excellent system
      for cell capture and nonenzymatic release.

PMID- 7516339
TI  - Inhibition of platelet spreading from plasma onto glass by an adsorbed layer of a
      novel fluorescent-labeled poly(ethylene oxide)/poly(butylene oxide) block
      copolymer: characteristics of the exclusion zone probed by means of polystyrene
      beads and macromolecules.
AB  - We have investigated the anti-adhesive properties of a newly synthesized
      fluorescent triblock copolymer containing poly(ethylene oxide). This adsorbs from
      aqueous solution onto glass that has been rendered hydrophobic. When the polymer
      treated surface was exposed to human platelet-rich plasma (PRP) or whole blood at
      37 degrees C, platelet adhesion and spreading were prevented. Avid adhesion and
      rapid platelet spreading occurred along tracks scraped in the adsorbed polymer
      coating, as seen by video-enhanced interference reflection microscopy. Leukocytes
      from whole blood are eventually able to adhere to the polymer-treated surface and
      were seen to remove labeled polymer from their vicinity and accumulate it at the
      cell body. Interferometry using polystyrene spheres showed that they do not
      adhere to polymer-coated glass and are unable to approach closer than 70-95 nm.
      On scraped tracks, beads make molecular contacts with the glass. Because the
      fully extended solvated (EO)400 arms may extend up to 100 nm from the glass, this
      suggests that the polymer forms a monolayer with the hydrophilic arms projecting
      into the water, whereas the hydrophobic (BO)55 segment binds the molecule to the
      hydrophobic surface. Another tri-bloc copolymer with shorter hydrophilic arms
      allows particles to approach more closely.

PMID- 7516340
TI  - Cytolocation of prosome antigens on intermediate filament subnetworks of
      cytokeratin, vimentin and desmin type.
AB  - Analysis by double-label indirect immunofluorescence of PtK1 and HeLa cells had
      previously demonstrated that prosome* antigens form networks that superimpose on
      those of the intermediate filaments of the cytokeratin type. We show here that in
      PtK1 cells various prosomal antigens also reside to a variable extent on
      intermediate filaments subnetworks of the vimentin type. In proliferating human
      fibroblasts the prosome and vimentin networks were found to coincide, while in
      proliferating myoblasts of the C2.7 mouse myogenic cell line the prosomal
      antigens seem to superimpose on the intermediate filaments of the desmin type.
      Thus, the prosomes, which are RNP particles of variable composition and
      subcomplexes of untranslated mRNP, and carry a multicatalytic proteinase
      activity, seem to co-localize with the specific kind of cytoplasmic intermediate
      filament in relation to the cell type. These results, which generalize the
      previous data, are discussed in view of possible role(s) for prosomes in mRNA
      metabolism and/or intermediate filaments remodelling.

PMID- 7516341
TI  - Molecular analysis of the gamma heavy chain of Chlamydomonas flagellar outer-arm
      dynein.
AB  - We report here the complete sequence of the gamma dynein heavy chain of the outer
      arm of the Chlamydomonas flagellum, and partial sequences for six other dynein
      heavy chains. The gamma dynein heavy chain sequence contains four P-loop motifs,
      one of which is the likely hydrolytic site based on its position relative to a
      previously mapped epitope. Comparison with available cytoplasmic and flagellar
      dynein heavy chain sequences reveals regions that are highly conserved in all
      dynein heavy chains sequenced to date, regions that are conserved only among
      axonemal dynein heavy chains, and regions that are unique to individual dynein
      heavy chains. The presumed hydrolytic site is absolutely conserved among dyneins,
      two other P loops are highly conserved among cytoplasmic dynein heavy chains but
      not in axonemal dynein heavy chains, and the fourth P loop is invariant in
      axonemal dynein heavy chains but not in cytoplasmic dynein. One region that is
      very highly conserved in all dynein heavy chains is similar to a portion of the
      ATP-sensitive microtubule-binding domain of kinesin. Two other regions present in
      all dynein heavy chains are predicted to have high alpha-helical content and have
      a high probability of forming coiled-coil structures. Overall, the central one
      third of the gamma dynein heavy chain is most conserved whereas the N-terminal
      one-third is least conserved; the fact that the latter region is divergent
      between the cytoplasmic dynein heavy chain and two different axonemal dynein
      heavy chains suggests that it is involved in chain-specific functions.

PMID- 7516342
TI  - Regulation of epithelial cell surface polarity reversal by beta 1 integrins.
AB  - The role of extracellular matrix in the regulation of epithelial cell surface
      polarity development was studied using MDCK cells. Previous work has demonstrated
      that MDCK cells cultured in suspension form epithelial cysts having polarized
      cell surface distributions of several membrane proteins. When MDCK suspension
      cysts are incubated within collagen gel, a dynamic epithelial membrane remodeling
      occurs that is accompanied by the reversal of cell surface polarity (Wang et al.,
      1990b, J. Cell Sci. 95, 153-165), suggesting that extracellular matrix is
      important in the modulation of epithelial polarity development. To determine if
      members of the integrin receptor family were involved, MDCK cyst binding studies
      were done utilizing antifunctional monoclonal antibodies (AIIB2 and AJ2) against
      the beta 1 integrin subunit. These antibodies inhibited cyst binding to type I
      collagen, type IV collagen and laminin, providing evidence that functional beta 1
      integrin heterodimers were present on the cyst outer membrane. Integrin
      localization on suspension cysts demonstrated that the alpha 2, alpha 3 and alpha
      6 integrin subunits had a non-polarized cell surface distribution and were
      localized to both the apical and basolateral membranes. Interestingly,
      immunofluorescence microscopy determined that the beta 1 subunit had a polarized,
      basolateral membrane distribution although cyst binding studies using inhibitory
      monoclonal antibodies suggested that functional beta 1 subunits were present on
      the cyst outer membrane. After incubation of suspension cysts in collagen gel for
      8 hours, the beta 1 integrin subunit was detected on the outer membrane,
      suggesting that the formation of additional integrin alpha/beta heterodimers
      could be involved in epithelial remodeling. To establish the role of beta 1
      integrins in polarity reversal, experiments were done on cysts incubated in
      collagen gel. After 6 hours in collagen gel, considerable membrane remodeling had
      occurred as determined by a reduction in outer membrane microvilli. However, the
      presence of monoclonal antibody AIIB2 inhibited membrane remodeling by preventing
      both microvillar loss and the endocytosis of the apical membrane glycoprotein
      gp135. These results provide strong evidence that members of the beta 1 integrin
      family are involved in the regulation of epithelial polarity reversal, and
      demonstrate that MDCK cysts constitute an excellent model system for studying the
      role of cell-extracellular matrix interactions in the regulation of epithelial
      plasticity and cell surface polarity development.

PMID- 7516343
TI  - Effect of some poly(ethylene glycol)-bound and dextran-bound affinity ligands on
      the partition of synaptic membranes in aqueous two-phase systems.
AB  - Ligands with an apparent affinity for various structural elements on the surface
      of synaptic membrane fragments have been bound to the polymers poly(ethylene
      glycol) and dextran. The ligand-polymer derivatives have been included in aqueous
      two-phase systems composed of water, poly(ethylene glycol) and dextran. The
      uneven distribution of the polymers resulted in the concentration of the polymer
      bound ligand in one of the two phases. The effect of the ligand-polymer on the
      partition of membranes was studied by using synaptic membranes from calf brain,
      obtained by standard centrifugation methods. By using ligand-containing two-phase
      systems for nine-step counter-current distribution of membranes, it was shown
      that the distribution behaviour of various parts of the membrane preparation
      could be affected. The distribution was followed by determination of opiate
      binding, acetylcholinesterase, and total membrane (using protein and light
      scattering measurements).

PMID- 7516344
TI  - Detection of feline immunodeficiency virus p24 antigen and p24-specific
      antibodies by monoclonal antibody-based assays.
AB  - A panel of monoclonal antibodies (mAbs) detecting distinct B-cell epitopes on p24
      core viral protein of feline immunodeficiency virus (FIV) were employed to
      develop immunoassays to measure p24 concentration in culture and serum samples,
      to localize p24 in FIV-infected cells and tissues, and to detect anti-p24
      antibodies in cat sera. In its optimized configuration the p24 capture assay
      detected as little as 0.25 ng/ml of protein. The assay was found at least as
      sensitive as the reverse transcriptase activity assay in FIV-infected lymphocyte
      cultures and proved capable of detecting p24 antigen in acid pretreated sera from
      a high proportion of FIV-infected cats. The mAbs were also successfully used to
      detect the p24 antigen in permeated FIV-infected cells by flow cytometry and in
      tissue sections from FIV-infected cats by immunohistochemical staining. Anti-p24
      antibodies in FIV-infected cat sera were assayed by a competitive capture ELISA
      which readily identified occasional false positive results provided by a standard
      ELISA using purified whole FIV-coated wells.

PMID- 7516345
TI  - PCR and reverse dot hybridization for the detection of endogenous retroviral
      transcripts.
AB  - Two degenerated oligonucleotide primers, known to amplify a fragment of the pol
      gene in all retroviruses tested so far have been used to amplify pol related
      sequences from human genomic DNA. Cloning and sequencing these fragments confirm
      a retroviral relationship for most of them and define 96 groups on the basis of
      their internal similarity. 96 pol fragments were probed with PCR amplified cDNA
      in reverse dot hybridization to investigate pol related transcripts. PCR
      amplified genomic DNA served as a control for contamination of genomic DNA in the
      RNA preparations. Isopycnic centrifugation in cesium trifluoroacetate yielded RNA
      with the lowest possible amounts of contaminating DNA. This technique is a
      powerful and a well-controlled tool for the detection of endogenous retroviral
      transcripts and may be helpful for investigating the involvement of endogenous
      retroviruses in various diseases.

PMID- 7516346
TI  - Predominant role for nitric oxide in the relaxation induced by acetylcholine in
      human uterine artery.
AB  - The effect of acetylcholine on the isolated human uterine artery rings was
      investigated. Acetylcholine (10(-10) M to 6 x 10(-5) M) induced concentration-
      and endothelium-dependent relaxation (pD2 = 7.4 +/- 0.02, maximal response was
      77.5 +/- 6.3% of relaxation induced by papaverine at 3 x 10(-4) M) of the pre
      contracted arterial segments. Indomethacin (10(-5) M), diethylcarbamazine (10(-4)
      M) and tetra-ethylammonium (3 x 10(-4) M) had no effects on acetylcholine-evoked
      relaxation. Methylene blue (10(-5) M) and NG-monomethyl-L-arginine (L-NMMA) (3 x
      10(-6) to 3 x 10(-5) M) antagonized relaxation induced by acetylcholine. The
      inhibition of endothelium-dependent relaxation by L-NMMA (10(-5) M) was reversed
      by L-arginine (10(-5) M) but not by D-arginine (10(-4) M). It is concluded that
      in uterine artery acetylcholine induces endothelium-dependent relaxation of
      isolated uterine artery is probably mediated via endothelial nitric oxide
      formation.

PMID- 7516349
TI  - Direct projections from the ventrolateral medulla oblongata to the limbic
      forebrain: anterograde and retrograde tract-tracing studies in the rat.
AB  - Neurons in the ventrolateral medulla oblongata, a brain region implicated in
      central vasomotor regulation, have previously been reported to project to some
      forebrain limbic structures. The aim of the present study was (1) to describe the
      termination pattern of ventral medullary afferents in forebrain limbic areas
      using anterograde tract tracing, and (2) to determine the location and some
      morphological characteristics of the projection neurons using retrograde tract
      tracing from selected forebrain sites. Following ionophoretic microinjections of
      the anterograde tract tracer Phaseolus vulgaris leucoagglutinin into the rostral
      ventrolateral medulla, labelled afferents were observed in the hippocampus,
      entorhinal and retrosplenial cortices, dorsal septum, nucleus accumbens, and the
      medial prefrontal cortex. Anterogradely labelled axons, ascending from the caudal
      ventrolateral medulla, could be traced only to the rostral aspects of the
      investigated forebrain limbic structures. Here, the main target of the ascending
      projection was in the ventral septum. However, labelled terminals were also
      present in the nucleus accumbens, the dorsolateral septum, and in the infralimbic
      cortex. The density of the ventrolateral medullary projections into all examined
      forebrain areas was low. The location of the cells in the ventral medulla
      oblongata which give rise to direct forebrain projections was examined using
      retrograde tract tracing with wheat germ agglutinin conjugated horseradish
      peroxidase (WGA-HRP). Following WGA-HRP injections into the septo-accumbens
      region, retrogradely labelled cells were present in both the rostral and caudal
      ventrolateral medulla. When the tract tracer injection was restricted to the
      ventral region of the septal complex, the labelled cells were concentrated in the
      caudal aspects of the ventrolateral medulla (and the nucleus of the solitary
      tract). Following tracer injections into the anterior cingulate cortex or the
      hippocampus or the entorhinal cortex, retrogradely labelled cells in the medulla
      oblongata were predominantly in the rostral ventrolateral medulla. As a first
      attempt to reveal the chemical nature of the projection cells, the contribution
      of tyrosine hydroxylase-immunoreactive cells to the innervation of the septo
      accumbens area was also investigated: tyrosine hydroxylase-immunoreactive cells
      of both the caudal ventrolateral medulla and the nucleus of the solitary tract
      were found to contribute to the innervation of the septo-accumbens area. The
      distribution of retrogradely labelled cells as well as the termination pattern of
      the anterogradely labelled terminals indicated that the innervation of the
      various forebrain limbic areas arises from cells, diffusely distributed in the
      rostral and/or the caudal ventrolateral medulla oblongata.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7516348
TI  - Induction of follicular growth and production of a normal hormonal milieu in
      spite of using a constant low dose of luteinizing hormone in women with
      hypogonadotrophic hypogonadism.
AB  - This study was designed to examine ovarian performance, i.e. follicular growth,
      normal steroidogenesis and luteal phase function, following the administration of
      multiple increasing doses of human follicle stimulating hormone (FSH) with a
      constant low dose of luteinizing hormone (LH) in women with isolated
      hypogonadotrophic hypogonadism. Human menopausal gonadotrophin (HMG) was used in
      the first treatment cycle, starting with 150 IU of LH and 150 IU of FSH per day,
      for 7 days. The dose was increased daily with 75 IU of LH and 75 IU of FSH for
      another 7 days if no response was detected by serial ultrasound measurements and
      serum oestradiol determinations. In the second treatment cycle, a constant dose
      of 75 IU of LH (using HMG) was administered per day and up to 150 IU of FSH
      (using urofollitrophin) was supplemented. If no response was detected after 7
      days of treatment, the dose of FSH was increased. For the final stage of
      ovulation induction, human chorionic gonadotrophin (HCG) was administered in the
      presence of at least one follicle > 17 mm in diameter but with no more than three
      follicles > 16 mm in diameter. To verify the adequacy of the luteal phase, a
      pharmacokinetic/pharmacodynamic study of beta-HCG, oestradiol and progesterone
      was performed following the second treatment cycle only. Ovarian stimulation
      using a constant dose of 75 IU of LH and increasing doses of FSH up to 225 IU,
      resulted in normal follicular growth and hormonal milieu. Both women showed
      normal luteal phase oestradiol and progesterone production and both women
      conceived following the second treatment cycle.

PMID- 7516347
TI  - Endometrial endothelial cell proliferation during the menstrual cycle.
AB  - Adult endometrium is a tissue in which physiological angiogenesis occurs
      regularly and provides an accessible source of material for study. Endometrial
      biopsies and immunohistochemistry were used to test two hypotheses: firstly, that
      there are peaks of endothelial cell proliferation in human endometrium during the
      menstrual cycle, and secondly that in-vitro endothelial cell migratory signal
      production by human endometrium (measured in a previous study) accompanies
      endothelial cell proliferative activity in vivo. Proliferating cells were
      identified using anti-proliferating cell nuclear antigen, and endothelial cells
      were identified using anti-CD34. The method was validated by a smaller, separate
      study using bromodeoxyuridine incorporation and detection with formalin-fixed
      biopsies, and comparison with proliferating cell nuclear antigen staining. The
      main study (n = 50) showed that significant peaks of endometrial endothelial cell
      proliferation could not be identified, due to the large variability in
      endothelial cell proliferative activity between individuals at the same stage of
      the menstrual cycle. Endometrial endothelial cell migratory signal production did
      not correlate with endothelial cell proliferation (n = 27). Results suggest that
      blood vessel growth in the endometrium may occur by a process that differs from
      the traditional concept of angiogenesis, which has been derived mainly from in
      vitro or in-vivo experimental studies.

PMID- 7516350
TI  - Compartmentation of glutamate and glutamine in the lateral cervical nucleus:
      further evidence for glutamate as a spinocervical tract neurotransmitter.
AB  - Previous observations indicate that spinocervical tract terminals contain
      relatively high levels of glutamate. To examine whether these high glutamate
      levels are likely to represent a neurotransmitter pool or an elevated metabolic
      pool, the distributions of glutamate- and glutamine-like immunoreactivities were
      examined in adjacent immunogold-labeled sections of the lateral cervical nucleus.
      Spinocervical tract terminals were identified by anterograde transport of
      horseradish peroxidase and wheat germ agglutinin-horseradish peroxidase conjugate
      from the spinal cord. Spinocervical tract terminals were found to contain
      significantly higher levels of glutamate-like immunoreactivity than other
      examined tissue compartments (large neuronal cell bodies, terminals with
      pleomorphic vesicles, astrocytes, and average tissue level). In contrast, the
      highest levels of glutamine-like immunoreactivity were detected in astrocytes.
      The different analyzed tissue elements formed three groups with respect to
      glutamate:glutamine ratios: one high ratio group including spinocervical tract
      terminals, a second group with intermediate ratios consisting of neuronal cell
      bodies and terminals containing pleomorphic synaptic vesicles, and a third low
      ratio group including astrocytes. Our findings indicate the presence of a
      compartmentation of glutamate and glutamine in the lateral cervical nucleus,
      similar to that postulated in biochemical studies of the central nervous system.
      The results also show that spinocervical tract terminals have high glutamate:
      glutamine ratios, similar to those previously observed in putative glutamatergic
      terminals in the cerebellar cortex. Thus, spinocervical tract terminals display
      biochemical characteristics that would be expected of glutamatergic terminals and
      the present findings therefore provide further evidence for glutamate as a
      spinocervical tract neurotransmitter.

PMID- 7516351
TI  - Localization of preganglionic neurons of the accessory ciliary ganglion in the
      midbrain: HRP and WGA-HRP studies in the cat.
AB  - Localization of preganglionic neurons of the accessory ciliary ganglion (ACG),
      including ectopic intraocular ganglion cells, was investigated in the cat with
      the aid of horseradish peroxidase (HRP) and HRP-conjugated wheat germ agglutinin
      (WGA-HRP) methods. When HRP or WGA-HRP was injected into the anterior and
      posterior chambers of the eye, no retrogradely labeled cells were found in the
      visceral oculomotor nuclei, although most neurons of the ACG and the main ciliary
      ganglion (CG) were intensely labeled. When a microsyringe needle was inserted
      into the ciliary body, the tracer diffused into the suprachoroid lamina and the
      intraocular ganglion cells, and a small number of labeled neurons appeared in the
      midplane between each side of the somatic oculomotor nuclei. After injection into
      the ACG, many labeled neurons were observed in the anteromedian nucleus, Edinger
      Westphal nucleus, and midplane between the somatic oculomotor nuclei, their
      ventral continuations of the ventral tegmental area, and the periaqueductal gray.
      HRP/WGA-HRP injection into the CG labeled cells in all these areas and in the
      lateral border zones of the anteromedian, Edinger-Westphal and somatic oculomotor
      nuclei, and their ventral continuations of the ventral tegmental area. These
      findings indicate that the visceral oculomotor neurons which project to the ACG
      tend to be located more medially than those to the CG.

PMID- 7516352
TI  - Atrioatrial conduction after orthotopic heart transplantation.
AB  - OBJECTIVES: In two patients with orthotopic heart transplantation, the surface
      electrocardiogram suggested interaction between the donor right atrium and the
      recipient right atrium. An electrophysiologic investigation was performed to
      assess possible atrioatrial conduction. BACKGROUND: After orthotopic heart
      transplantation, both recipient and donor atrial activities are usually
      independent, but in humans they may synchronize for short periods during
      exercise. METHODS: Electrophysiologic recordings were made using standard
      techniques. The atrial electrode locations (anterior for the donor and posterior
      for the recipient right atria) were confirmed by fluoroscopy. Incremental and
      programmed donor and recipient right atrial pacing protocols were performed.
      RESULTS: Unidirectional conduction between native and graft atria occurred in
      both patients. This phenomenon was evident at rest, during normal sinus rhythm
      and at various pacing rates, resulting in frequent atrial bigeminy and trigeminy.
      CONCLUSIONS: Possible atrioatrial conduction after orthotopic heart
      transplantation may potentially be arrhythmogenic for the chamber where
      extrasystoles occur. This should be taken into account in attempting to devise
      new pacing modes if both atria are rendered electrically common.

PMID- 7516353
TI  - Angiogenesis and low molecular weight heparin.

PMID- 7516354
TI  - Subnormal albumin gene expression is associated with weight loss in
      immunodeficient/DNA-repair-impaired wasted mice.
AB  - OBJECTIVE: Mice bearing the autosomal recessive mutation wst express a disease
      syndrome of immunodeficiency, neurologic dysfunction, increased sensitivity to
      the killing effects of ionizing radiation, and dramatic weight loss that begins
      at 21 days of age and progresses until death at 28-32 days of age. Because of the
      reported association between abnormal liver status and weight loss, we designed
      experiments to examine expression of a variety of liver-specific genes in wst/wst
      mice relative to littermates (wst/.) and parental strain (BCF1) controls. METHOD:
      Animals were individually weighed from ages 21-28 days to determine relative
      weight comparisons between wst/wst mice and controls. Dot blot hybridizations
      were set up to quantitate the accumulation of transcripts specific for alpha
      fetoprotein, albumin and other liver-specific gene products. RESULTS: These
      results showed a 67% reduction in albumin mRNA expression in livers derived from
      wst/wst mice relative to both controls. Expression of alpha-fetoprotein, as well
      as a variety of other liver-specific genes [secretory component (SC),
      metallothionein (MT-2), cytochrome P1-450 (Cyt P1-450), transferrin receptor (Tf
      Rec), tumor necrosis factor (TNF), and immune-associated antigen (Ia)], was
      unaffected. CONCLUSIONS: These results suggest a relationship between low albumin
      expression and wasting syndromes in mice. In addition, our data suggest that the
      wasted mouse may serve as a unique model for subnormal albumin expression.

PMID- 7516355
TI  - Possible dual role of anti-idiotypic antibodies in combined passive and active
      immunotherapy in honeybee sting allergy.
AB  - BACKGROUND: Passive infusion of beekeepers' plasma was shown to protect patients
      against systemic reactions occurring during active immunotherapy by mechanisms
      still to be clarified. It is tempting to speculate that anti-idiotypic antibodies
      could play a role because they are found in beekeepers' plasma and are involved
      in the regulation of IgE synthesis. METHODS: In this report we studied the
      effects of passive infusion of a beekeeper's plasma rich in anti-idiotypic
      antibodies to a patient who experienced systemic reactions to honeybee venom.
      RESULTS: We reported, during the days after the infusion, a decrease of clinical
      sensitivity to the honeybee venom. Indeed, the patient tolerated a cumulative
      dose of 280 micrograms of venom without adverse reactions. We also observed
      decreases in skin mast cell and in basophil sensitivity. After the plasma
      infusion, a modified rush immunotherapy with honeybee venom was initiated in our
      patient. In the following 76 weeks, increased levels of anti-idiotypic antibodies
      in the serum of the patient were associated with a diminution of specific
      antibodies (IgG and IgE) to honeybee venom. CONCLUSION: These results suggest a
      dual role of anti-id in our combined protocol of passive and active
      immunotherapy: an immediate action on clinical sensitivity along with a decrease
      of skin mast cell and basophil sensitivity and an immunoregulatory role on
      specific antibody production.

PMID- 7516356
TI  - Antithyroid drug-induced agranulocytosis: clinical experience with ten patients
      treated at one institution and review of the literature.
AB  - The frequency, predisposing factors and course of agranulocytosis (granulocytes <
      250/microliter) secondary to antithyroid drugs were studied in a cohort of 1256
      continuously treated outpatients with hyperthyroidism during the 15 year period
      from 1973 to 1987. Two cases of agranulocytosis were detected; the frequency was
      0.18% (95%-confidence intervals, 0.0-0.44%). This prevalence appears to be lower
      than reported in previous studies (up to 1.8%). For other adverse drug reactions,
      there was a clear-cut relationship to initial thionamide dose and to the body
      mass index; most reactions occurred during the first weeks of treatment. In
      addition, eight patients referred for thionamide drug- induced agranulocytosis
      were studied, and the following results obtained: Methimazole dose in patients
      with agranulocytosis was almost twice as in other patients (63.3 +/- 19.7 vs 34.3
      +/- 29.7 mg daily) suggesting that this complication was related to dose. The
      interval between start of antithyroid drug treatment and first symptoms of
      agranulocytosis was 33 days (median; range, 23-55 days); hence, prolonged
      treatment beyond this period would appear relatively safe. Withdrawal of the
      causative agent and treatment of infection led to recovery of leukocyte counts
      within 15 days (median; range, 5-31 days). Two fatal outcomes were seen in
      referred patients. In one severely hyperthyroid patient with methimazole-induced
      agranulocytosis, recombinant human granulocyte/macrophage colony stimulating
      factor induced clinical and hematologic recovery within a few days of
      administration. In conclusion, agranulocytosis is the most severe side effect of
      antithyroid drugs. According to our results and a literature review, it occurs
      almost exclusively during the first ten weeks of treatment and is probably
      related to the drug dose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516358
TI  - Effects of luxabendazole on the tegument of Fasciola hepatica.
AB  - The effects in vivo of 5, 10, and 20 mg/kg of luxabendazole (LBZ) on the tegument
      of Fasciola hepatica have been examined 48 h, 7 days and 14 days post-treatment
      of experimentally-infected rats. As early as 48 h post-treatment, the drug is
      shown to provoke significant damage to the tegument. The pathological phenomena
      characterizing LBZ damage are blebbing of the apical plasmalemma, formation of
      microvillus-like projections over the free surface, swelling of the basal infolds
      and stimulation of autophagy. The spines are often fractured; the tegument in the
      vicinity of spines seems more strongly altered than that in other foci. The basal
      layer is often changed, from increase of electron density to lack of integrity
      with the apical cytoplasm. The progress of the ultrastructural damage with time
      is not expressed. However, cytochemical data show that a longer post-treatment
      intervals the surface-coat structure becomes irregular and patches of ruthenium
      red positive material of variable thickness are focally accumulated. Only a
      slight dose-effect is noted 48 h after LBZ application when the alterations
      provoked by 5 mg/kg are less evident than those by 10 and 20 mg/kg.

PMID- 7516357
TI  - Cross-reactive antibodies in the serum of balb/c mice immunized with thyroid or
      eye muscle membranes.
AB  - During the course of immunizing balb/c mice with eye muscle (EM) or thyroid (THY)
      membranes for monoclonal antibody (MCAB) production their sera frequently contain
      antibodies which react against both EM and THY membranes in enzyme-linked
      immunosorbent assay (ELISA) and SDS-polyacrylamide gel electrophoresis (SDS-PAGE)
      and Western blotting. In order to further study this phenomenon we have analyzed
      sera from 27 balb/c mice, including 10 that were studied serially, and their
      tissues examined histologically at sacrifice. Following immunization serum and,
      in some cases, the corresponding MCAB produced by fusion of the mouse spleen
      cells with a mouse myeloma cell line, were tested for EM and THY cross-reactivity
      in an ELISA and by immunoblotting. The number of antibodies demonstrated in
      Western blotting identified as bands of reactivity, and ELISA levels, expressed
      as optical density--increased with time, each peaking at around 10-12 weeks. THY
      and EM antibody cross-reactivity was demonstrated in the majority of mice, serum
      from mice immunized with THY membranes reacting with these membranes as well as
      with pig EM membranes in both ELISA and immunoblotting and, conversely, sera from
      mice immunized with pig EM membranes also reacting with THY membranes in the two
      tests. In Western blotting a variety of THY and EM-reactive antibodies were
      demonstrated including those directed against a 64 kDa protein, shown to be an
      important autoantigen in thyroid-associated ophthalmopathy. There was also some
      cross-reactivity with brain membranes, used as control antigen in both tests and
      in immunization, although to a lesser degree, but very little to liver and
      orbital connective tissue membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516359
TI  - Adenosine triphosphate protection of chlordecone-amplified CCl4 hepatotoxicity
      and lethality.
AB  - Dietary exposure to a nontoxic level of chlordecone (10 ppm for 15 days) followed
      by a single exposure to a subtoxic dose of CCl4 (100 microliters/kg, ip) is known
      to result in a 67-fold amplification of CCl4 toxicity. The hypothesis that the
      underlying mechanism is due to incapacitation of hepatocytes leading to an
      ablation of the early-phase hormetic response of tissue repair as a consequence
      of precipitous decline in hepatic glycogen and ATP, received experimental support
      from Mehendale in 1990. The present study was designed to investigate if direct
      administration of ATP to rats maintained on the chlordecone diet would result in
      protection from the hepatotoxic and lethal effects of the chlordecone+CCl4
      combination. Male Sprague-Dawley rats (125-150 g) were maintained either on a
      diet containing no added contaminants (control) or on a diet containing 10 ppm
      chlordecone for 15 days, and were challenged with CCl4 (100 microliters/kg, ip)
      on day 16. Without ATP administration all rats died within 72 h, while
      administration of ATP (100 mg/rat, sc) to chlordecone-pretreated rats at -1, +1,
      3, 5, 12, 24 and 36 h of CCl4 injection resulted in 100% survival. Injection of
      ATP, at -1, +1, 3 and 5 h of CCl4 administration to chlordecone pretreated rats
      decreased plasma enzyme elevations (alanine and aspartate aminotransferase,
      sorbitol dehydrogenase) as well as substantially preventing elevation of plasma
      bilirubin levels at 6, 12 and 24 h. Hepatic ATP levels were also elevated at 6
      and 12 h, but not at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516360
TI  - Detection of hepatitis C virus antigen by immuno-histochemical staining: a
      histological marker of hepatitis C virus infection.
AB  - Hepatitis C virus has been recognized as a major cause of non-A, non-B viral
      hepatitis. Although serologic tests have been commercialized, no specific
      histological or immuno-histochemical markers for hepatitis C virus infection are
      available for routine use. In an effort to detect hepatitis C virus antigen in
      liver tissue we investigated the immuno-reactivity to monoclonal antibodies on
      frozen liver tissue from a chimpanzee and patients with chronic non A, non B
      hepatitis. Monoclonal antibodies were developed in mice immunized with a
      synthetic peptide derived from hepatitis C virus core antigen. One monoclonal
      antibody was reactive and showed typical cytoplasmic granules in chimpanzee
      hepatocytes. Using this monoclonal antibody a similar staining pattern was found
      in the liver biopsies of 21 out of 28 chronic non-A, non-B hepatitis patients,
      positive for hepatitis C virus-RNA and anti-HCV. The granular immuno-reactivity
      was abolished after pre-incubation of this monoclonal antibody with infected
      chimpanzee liver or with hepatitis C virus synthetic peptide but not with normal
      chimpanzee or human liver tissue. There was no reactivity in four patients with
      hepatitis C virus-RNA-negative, anti-HCV-positive chronic non-A, non-B hepatitis,
      in 11 patients with chronic type B hepatitis or in 12 hepatitis C virus-RNA
      negative, anti-HCV-negative patients with various liver diseases. However,
      staining was found in three out of four additional chronic type B hepatitis
      patients suspected of co-infection with non-A, non-B agents.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7516361
TI  - Total paracentesis with dextran 40 vs diuretics in the treatment of ascites in
      cirrhosis: a randomized controlled study.
AB  - The aim of the current study was to compare total paracentesis associated with
      dextran-40 infusion with diuretics in the treatment of tense ascites in patients
      with cirrhosis. Eighty patients were randomly allocated to two groups: 40
      patients were treated with paracentesis plus dextran-40 infusion (8 g per liter
      of ascitic fluid removed), and 40 patients with diuretics. After treatment
      patients were discharged with diuretics, and patients developing tense ascites
      during follow up (54 +/- 4 weeks) were treated according to their initial
      schedule. Paracentesis was more effective than diuretics in mobilizing the
      ascitic fluid. The incidence of complications was significantly higher (p < 0.05)
      in the diuretic group (38%) than in the paracentesis group (15%). This difference
      was mainly due to a higher incidence of hepatic encephalopathy in the former
      group (30% vs. 2.5%). A significantly higher incidence of hepatic encephalopathy
      was also observed in the diuretic group during the follow-up readmissions for
      ascites recurrence. There were no significant differences between the two
      treatment groups in the probability of survival after inclusion. Plasma renin
      activity and plasma aldosterone concentration measured before and 2 and 6 days
      after paracentesis in 20 randomly selected patients increased significantly (p <
      0.05) (baseline values: 5.3 +/- 1.4 ng.ml-1.h-1 and 63 +/- 21 ng/dl; 48 h after
      paracentesis: 11.7 +/- 3.9 ng.ml-1.h-1 and 99 +/- 31 ng/dl; 6 days after
      paracentesis: 10.9 +/- 3 ng.ml-1.h-1 and 110 +/- 27 ng/dl).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7516362
TI  - Early prediction of successful alpha-interferon therapy of chronic hepatitis C by
      core-IgM antibodies to hepatitis C virus.

PMID- 7516363
TI  - Inhibition of hepatitis B virus replication by adenine arabinoside monophosphate
      coupled to lactosaminated albumin. Efficacy and minimal active dose.

PMID- 7516364
TI  - Prevalence of antibodies to hepatitis C virus in Greek patients with chronic
      liver disease.

PMID- 7516365
TI  - [Non Surgical Treatment of Benign Prostatic Hyperplasia. Proceedings of an
      international symposium. Aquila, Italy, 30 April 1993].

PMID- 7516366
TI  - [Non surgical treatment of benign prostatic hypertrophy].

PMID- 7516368
TI  - [Clinical aspects of benign prostatic hypertrophy].

PMID- 7516367
TI  - [Epidemiological aspects of benign prostatic hypertrophy].

PMID- 7516369
TI  - [Non surgical treatment of benign prostatic hypertrophy: phytotherapy].
AB  - Pharmacological treatment of voiding disorders due to benign prostatic
      hypertrophy offers a wide variety of pharmacological options. Phytotherapy
      represents one of the oldest drug used in the treatment of BPH. In the last
      decade, many studies have been performed to demonstrate efficacy and tolerability
      of this drug. We report a short literature review on mechanism of action and
      objective and subjective results of treatments with plant extracts. We report on
      a comparation between literature data and data of our trials. Safety,
      tolerability and subjective results seems to indicate that plant extract are
      still a good pharmacological option in the treatment of BPH micturitional
      disorders.

PMID- 7516370
TI  - [Mepartricin as medical treatment of benign prostatic hypertrophy].

PMID- 7516372
TI  - [Finasteride in the treatment of benign prostatic hypertrophy].
AB  - Finasteride acts by blocking the conversion of testosterone to 5a
      dihydrotestosterone, the active androgen metabolite in the human prostate. In
      large, double-blind, placebo-controlled phase III-studies recruiting over 1,600
      patients, it was shown that the administration of Finasteride, either 5 or 1 mg a
      day, reduced the size of the prostate by a mean of 22%, following 6 months of
      therapy. Despite this reduction in prostate size, urinary flow rate only improved
      by a mean of 1.7 ml per second, and symptom score improved only marginally, but
      statistically significantly different from placebo. The future role for
      Finasteride therapy is emerging but it appears as if patients with mild to
      moderate symptoms would be a group who could benefit the most. Whether or not
      Finasteride can stop the long-term natural course of benign prostatic hyperplasia
      has still to be demonstrated.

PMID- 7516371
TI  - [Androgen deprivation in benign prostatic hypertrophy].
AB  - Benign prostatic hypertrophy is the cause of urinary outflow obstruction in the
      majority of men older than 50 years. Even if the pathophysiology of BPH is
      multifactorial, its development needs testicular androgens and aging. Androgen
      deprivation is the only approach that may reduce the hyperplastic state. This
      article reviews the endocrine aspect of BPH and the various hormonal treatment
      strategies, concerning clinical efficacy and side effects.

PMID- 7516374
TI  - [Aromatase inhibitors in the medical treatment of benign prostatic hypertrophy].

PMID- 7516373
TI  - [Physiopathological aspects of the treatment of benign prostatic hypertrophy.
      Role of prostatic stroma and estrogens].
AB  - The hypothesis of the etiopathogenesis of Benign Prostatic Hypertrophy (BPH) on
      the basis of stroma-epithelium interaction is presented. The fetal prostate has
      its origin in the urogenital sinus depending on the dehydrotestosterone
      stimulating the stromal cells having androgenic receptors. This stroma
      hyperplasia is considered to be the initial factor in the BPH formation. The
      inequality in growth factors is also relevant for its formation. Stimulating
      factors, especially the epidermal growth factor (EGF) prevail on involution
      factors. The stromal cell has estrogenic receptors. The estrogens from the
      testosterone aromatization are the first stimulus on the prostatic stroma on the
      transitional and periurethral area stimulating the glandular epithelium causing
      BPH. The knowledge of BPH etiopathogenesis will make its rational medical
      treatment possible, and eventually slow or stop its growth when therapy in its
      early evolutive stages is prescribed.

PMID- 7516376
TI  - [Terazosine in the treatment of benign prostatic hypertrophy].
AB  - A review is presented of the current status of terazosin in the treatment of BPH.
      The results of many clinical trials indicate a definite and significant
      improvement in both subjective and objective parameters. Attention is drawn to
      certain possible problems and limitations of placebo controlled trials with alpha
      adrenergic blockers for BPH. Parameter improvements appear to be dose-related,
      and the importance of dose titration is stressed. The pharmacokinetic properties
      of the drug enables a once daily administration. Long term treatment for more
      than two years indicates that efficacy is maintained.

PMID- 7516375
TI  - [Alfuzosin in the treatment of benign prostatic hypertrophy].

PMID- 7516377
TI  - [Doxazosin in the treatment of benign prostatic hypertrophy].

PMID- 7516378
TI  - [Pharmacological combinations in the treatment of benign prostatic hypertrophy].
AB  - In the development of the obstructive symptomatology of benign prostatic
      hypertrophy (BPH), two components may be identified, mechanical and dynamic. In
      the mechanical component, the interaction of a stromal and a epithelial
      compartment determines prostatic mass growth. The dynamic component involves
      smooth muscle tone in the prostate and urethra. The consideration that prostatic
      disease is not only epithelial in origin, but also stromal, leads to the
      association of an antiandrogen (which acts on the epithelial component) and an
      antiestrogen (active on the stromal component) in the medical therapy of BPH. In
      1985 we carried out a randomized study on 256 BPH patients treated with
      Cyproterone acetate (CPA) plus Tamoxifen (TAM). Recently, we performed a
      multicenter double blind study on BPH patients treated with the association CPA
      plus Serenoa Repens. A statistically significant difference in prostate volume
      reduction between the groups treated with the combinations and those with the
      monotherapies was observed. The development of new compounds, such as 5 alpha
      reductase and aromatase inhibitors, consents to introduce a combination therapy
      with less side effects. A second pharmacological association may be obtained with
      drugs acting on the mechanical and others acting on the dynamic (alpha blockers)
      component of BPH. This combination may associate the early symptomatic effect of
      alpha blockers with the long term results of a 5 alpha reductase inhibitor,
      antiestrogen or aromatase inhibitor.

PMID- 7516379
TI  - [The intraurethral catheter. A 3-year experience].
AB  - One hundred and thirty prostatic stents were inserted in 94 patients with benign
      prostatic hyperplasia. Seventy eight of these patients (83%) had an indwelling
      catheter because of chronic urinary retention. The other 16 patients had severe
      obstructive symptoms. Of the 130 IUCs inserted, 80.8% were successful. Fifty
      three stents were left for 1 to 6 months and 52 remained in place for 6 to 19
      months. All patients were continent. The IUC may be an alternative to surgery in
      patients with a high risk for prostatectomy, or may replace an indwelling
      catheter until surgery is possible.

PMID- 7516380
TI  - [Intraprostatic prostheses].
AB  - Intraprostatic stents appeared as an alternative to surgery in high surgical risk
      obstructed patients. A critical review of the different types of endoprostatic
      prostheses is made. Finally we tried to establish the true cost/effectiveness
      ratio in our country, comparing the temporary prostheses with the indwelling
      catheter and the permanent prostheses with prostatic surgery.

PMID- 7516381
TI  - [Long-term temporary prosthesis in prostatic obstruction. ProstaCoil, an
      expanding, self-fixating implant of large caliber].
AB  - The spiral metallic stent for insertion into the prostatic urethra developed by
      Fabian a decade ago, and its various modifications have a fixed external caliber
      of up to 21F and does not allow passage of instruments larger than 5-6F through
      it. Thus, they cannot be used in patients who need frequent trans-urethral
      manipulations. Since all temporary prostatic stents, in the long term develop
      incrustations they have to be changed once a year, or earlier, if they become
      occluded by stone formation. Permanent stents cannot be used in patients who are
      temporarily unfit for surgery because their removal necessitate traumatic
      manipulations. In order to overcome these disadvantages, a new large caliber,
      self-expanding and self-retaining intra-prostatic stent was developed
      (ProstaCoil). This stent is inserted under fluoroscopic guidance using topical
      anaesthesia. During the last 36 months the ProstaCoil was inserted into 65
      patients suffering from complete prostatic obstruction due to BPH. Follow-up of
      our patients was 3-28 months (mean 16 months). Forty-eight patients could void
      either immediately or within 48 hours after insertion of the stent. Thirty
      patients underwent TURP or open prostatectomy 3-12 months after insertion of the
      stent. In all these cases the stent was removed easily before surgery. Only in 1
      case the stent was removed because of severe urge incontinence. Seven patients
      died during this period. Twenty-seven patients still are passing urine through
      their stents (the longest 32 months).

PMID- 7516382
TI  - [The Wallstent prosthesis in the treatment of prostatic obstruction].

PMID- 7516383
TI  - [The ASI Titane intraprostatic implant].

PMID- 7516384
TI  - [Experience with prostatic hyperthermia].

PMID- 7516386
TI  - [Transurethral thermotherapy by radiofrequency at various temperatures in benign
      prostatic hypertrophy. Clinical experience with Thermex II Direx].
AB  - Over 2 years, 191 patients with symptomatic benign prostatic hypertrophy (BPH)
      have been treated by transurethral radiofrequency heating of the prostate at
      various temperatures (44.5 and 47-48 degrees C) in one session. At 44.5 degrees
      C, 60% of the patients were subjectively improved and 71% at 47-48 degrees C. 58%
      of the patients in retention were catheter free after treatment. The mean
      increase in the peak flow was not significant no matter the temperature used. A
      subjective improvement is obviously demonstrated by the significant decrease in
      the overall symptom score and essentially by the reduction in the irritative
      symptoms such as nocturia and urgency. This new alternative approach may play a
      meaningful role in the symptomatic management of selected patients with BPH.

PMID- 7516385
TI  - [Transurethral thermotherapy by microwaves in patients with benign obstructive
      prostatic hypertrophy].
AB  - The effect of transurethral microwave thermotherapy (TUMT) with Prostatron in
      patients with benign prostatic hypertrophy was investigated. Two hundred and one
      patients were treated between January 1991 and June 1992 after informed consent
      was signed. The following examinations were carried out at screening: interview
      (including symptoms score evaluation), physical examination (including digital
      rectal examination), haematology and blood chemistry (including prostate specific
      antigen), ECG, chest Xray, kidney, bladder and prostate (transrectal) ultrasound
      sonography (USS) and uroflowmetry; pressure-flow study was performed in a
      selected group of patients. All enrolled patients had Madsen symptom score > or =
      8; peak flow rate < or = 15 ml/s and post void residual urine < or = 200 ml.
      Patients with obstructive middle lobe of the prostate, any BPH complication or
      any suspicion of prostatic carcinoma were excluded from the study. Microwave
      thermotherapy with Prostatron was carried out according to software generation
      2.0 (Prostasoft 2.0), the c10 (black) catheter was used in all patients. Follow
      up visits were scheduled at 1 week, 1, 3, 6, 12, 18 months after microwave
      thermotherapy. Overall short- and long-term morbidity rates were 6.09 and 2.73
      per cent, respectively. At 12 months, Madsen score was found to be reduced from
      11.7 +/- 4.78 to 4.43 +/- 3.30; maximum flow rate (Qmax) was increased from 8.91
      +/- 4.20 to 13.20 +/- 4.86; post void residual urine (PVRU) was reduced from 131
      +/- 17.6 to 67.40 +/- 34.50.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516387
TI  - [Tissue ablation by high-intensity focused ultrasound in benign prostatic
      hypertrophy].

PMID- 7516388
TI  - [Ablation of the prostate by laser (ELAP)].

PMID- 7516389
TI  - [Therapy by endoscopic laser for prostatic obstruction].
AB  - As part of the search for alternatives to transurethral resection of the prostate
      (TURP) attention has (re)turned to laser methods. We describe our experience with
      the currently available endoscopic beam deflection devices, particularly the
      Prolase II. 25 patients, generally with medical reasons to avoid TURP, and with
      proven bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPH)
      underwent prostatic laser coagulation. Average age was 72 years (range 57-84),
      mean prostatic size by transrectal ultrasound (TRUS) was 48 g (15-100), average
      pretreatment peak flow rate (FR) was 7.6 ml/s (4.56-12.4). All patients were
      markedly symptomatic. Patients underwent clinical examination, Prostate specific
      antigen assay (PSA = 3.75, range 0.1-10.2), and TRUS preoperatively to exclude
      prostate cancer. After cystoscopic assessment the prostate was lasered according
      to the device manufacturers recommendations and clinical experience. A suprapubic
      catheter (SPC) and urethral catheters were inserted, the urethral for 24 hours.
      If voiding was satisfactory the SPC was removed after 24-48 hrs. Alternatively
      the patient was discharged and assessed at weekly intervals for SPC removal. Mean
      duration of SPC drainage was 11 days. Total mean impatient stay was 4.5 days (2
      13) during a mean of 2 admissions. Blood loss was minimal and there were no other
      significant complications. At a minimum follow up of 3 months mean peak FR was
      15.3 ml/s (9-31). Symptom scores (IPSS) fell from a mean of 21 to 10 by 3 months
      after treatment. There was an initial period of irritability for up to 12 weeks
      but symptomatic improvement was noted in all.

PMID- 7516390
TI  - [Extracorporeal shock waves. An alternative to hyperthermia for the treatment of
      benign prostatic hypertrophy].

PMID- 7516391
TI  - [New technologies for the treatment of benign prostatic hypertrophy: bases for
      change].

PMID- 7516392
TI  - [Current state of the surgical treatment of benign prostatic hypertrophy].

PMID- 7516393
TI  - [Medicolegal aspects of non-surgical treatment of benign prostatic hypertrophy].

PMID- 7516394
TI  - [Non surgical treatment of benign prostatic hypertrophy. Past, present and
      future].

PMID- 7516395
TI  - Characterization of expression and modulation of cell adhesion molecules on an
      immortalized human dermal microvascular endothelial cell line (HMEC-1).
AB  - We have recently reported the creation of the first immortalized cell line
      derived from human dermal microvascular endothelial cells (HMEC-1). In
      preliminary studies this line was found to closely resemble microvascular
      endothelial cells in regard to many phenotypic characteristics. Because two key
      functional features of endothelial cells are their ability to bind to peripheral
      blood leukocytes and extracellular matrix proteins via cell adhesion molecules,
      we have now characterized HMEC-1 in terms of expression and regulation of cell
      adhesion molecules of the integrin, immunoglobulin gene superfamily, and selectin
      families. HMEC-1 can either constitutively express or can be induced to express
      key integrins, including alpha-1, -2, -3, -4, -5, -6, and -V, as well as beta-1, 
      3, -4, and -5. They also express or are capable of expressing immunoglobulin gene
      superfamily molecules, such as intercellular adhesion molecule-1 and vascular
      cell adhesion molecule-1, and a member of the selectin family, E-selectin. A
      number of important cell adhesion molecules that are either constitutively
      expressed or that must be induced are regulated in a time- and dose-dependent
      fashion by selected cytokines. Experiments comparing the phenotypic
      characteristics of HMEC-1 with human dermal microvascular endothelial cells or
      human umbilical vein endothelial cells reveal HMEC-1 to have features of both
      small- and large-vessel endothelial cells.

PMID- 7516397
TI  - Retinoic acid suppression of loricrin expression in reconstituted human skin
      cultured at the liquid-air interface.
AB  - Retinoids have been shown to modulate the expression of proteins involved in
      epidermal differentiation. To examine this effect in an in vitro skin model, we
      evaluated the effect of retinoic acid on the expression of two cell envelope
      proteins, loricrin and involucrin, and an early marker of epidermal
      differentiation, keratin 1, in a reconstituted human skin equivalent cultured at
      the liquid-air interface. Retinoic acid, a known inhibitor of keratinization in
      monolayer and raft cultures, was evaluated for its ability to alter the
      expression and distribution of these markers of epidermal differentiation.
      Retinoic acid (10(-6) M) suppressed loricrin expression in skin cultures as
      determined by both protein and mRNA analysis. In contrast, no inhibition of
      involucrin or K1 expression was observed at the protein level at the same
      retinoic acid concentration. However, some suppression of K1 mRNA transcription
      was observed in retinoic acid-treated cultures. These results demonstrate that in
      differentiating cultures of reconstituted human skin, loricrin expression is
      markedly inhibited by retinoids, K1 less so, and involucrin not at all.

PMID- 7516396
TI  - Development of an ELISA to detect anti-BP180 autoantibodies in bullous pemphigoid
      and herpes gestationis.
AB  - Autoantibodies associated with the subepidermal blistering disorders bullous
      pemphigoid and herpes gestationis react with a 180-kD transmembrane
      hemidesmosomal protein, designated BP180. The BP180 ectodomain is composed of a
      series of interrupted collagen triple helical domains. Located on one of the
      noncollagenous extracellular segments of this protein is an immunodominant
      epitope, designated MCW-1, recognized by patient autoantibodies. In this
      investigation we have developed an enzyme-linked immunosorbent assay system to
      detect antibody reactivity against the MCW-1 epitope with the use of a bacterial
      fusion protein containing the BP180 autoantibody-reactive site. The following
      sera were assayed for reactivity with this recombinant protein: bullous
      pemphigoid (n = 62), herpes gestationis (n = 28), endemic pemphigus foliaceus (n
      = 17), lupus erythematosus (n = 15), and normal human sera (n = 22). This enzyme
      linked immunosorbent assay-based protocol was shown to be highly specific (98.3%)
      in detecting autoantibody activity in bullous pemphigoid and herpes gestationis
      patients. Fifty-three percent of bullous pemphigoid sera and 71% of herpes
      gestations sera, but none of the control sera, yielded positive results in this
      assay. Of the patient sera that were known to react with full-length BP180,
      almost all showed reactivity with the MCW-1 antigenic site of this protein.
      Autoantibodies detected in this assay were predominantly of the immunoglobulin G
      class. The results presented here lend support to the hypothesis that this well
      defined antigen/antibody system may be relevant in pathogenesis.

PMID- 7516399
TI  - Localization of type I human skin collagenase in developing embryonic and fetal
      skin.
AB  - Type I human skin collagenase (HSC-1) was localized in developing embryonic and
      fetal skin ranging from 6 to 20 weeks estimated gestational age using an antigen
      specific, affinity-purified, polyclonal antiserum to HSC-1 and an avidin-biotin
      alkaline phosphatase procedure. Double immunolabeling with monoclonal antibodies
      for Factor VIII-related antigen, type IV collagen, and the 68-kilodalton
      neurofilament subunit was performed using a direct peroxidase procedure. By 8
      weeks estimated gestational age, HSC-1 localized to the periderm, the basal cell
      epidermal keratinocytes, dermal fibroblasts, and surrounding extracellular
      matrix. At 12 weeks estimated gestational age, HSC-1 immunolabeling showed a
      continued association with the epidermis and dermis. Dermal and subcutaneous
      blood vessels and the surrounding extracellular matrix were positive for HSC-1
      labeling. HSC-1 staining was also found around developing nerves and in
      association with dermal fibroblasts. In the developing hair follicle, HSC-1 was
      present in keratinocytes of the pre-germ, germ, hair peg, and bulbous hair peg.
      HSC-1 immunoreactivity was also found in association with the hair canal, the
      bulge, and the dermal papillae, but was absent from the fetal sebaceous gland.
      These data demonstrate the association of HSC-1 with the development of
      interfollicular epidermis, the dermal collagenous matrix, the process of
      angiogenesis, the development of nerves, and hair follicle morphogenesis.

PMID- 7516398
TI  - The chemokine RANTES is more than a chemoattractant: characterization of its
      effect on human eosinophil oxidative metabolism and morphology in comparison with
      IL-5 and GM-CSF.
AB  - Eosinophils were shown to play a major role in the allergic inflammatory process
      leading to the clinical symptoms of atopic dermatitis. Only selected cytokines
      are capable of inducing a chemotactic response in eosinophils. In particular, the
      chemokine RANTES was recently shown to be a potent eosinophil chemotaxin. To
      examine the role of RANTES in eosinophil activation, we investigated the effect
      of RANTES and other chemokines on morphology and oxidative metabolism of highly
      purified eosinophils of normal nonatopic blood donors by assessment of functional
      as well as morphologic criteria. RANTES, and, to a lesser extent, MIP-1 alpha
      significantly induced the production of reactive oxygen species by human
      eosinophils, whereas MCP-1, MIP-1 beta, and interleukin (IL)-8/NAP-1 had no
      significant effects. RANTES stimulated only a subpopulation of the normal
      eosinophils. With the exception of IL-8, none of the cytokines tested had any
      significant effect on polymorphonuclear neutrophilic granulocytes. By scanning
      electron microscopy, RANTES induced characteristic changes that were completely
      abrogated in the presence of cytochalasin B. Based on functional and
      ultrastructural assays significant extracellular but not intracellular H2O2
      production was detected and completely inhibited by cytochalasin B. Separation of
      eosinophils by discontinuous density gradients revealed the existence of two
      hypodense eosinophil populations, one which showed significantly reduced
      responses upon stimulation with RANTES. RANTES-induced production of reactive
      oxygen species was almost completely inhibited by staurosporine, wortmannin, or
      pertussis toxin. Based on these data it is evident that RANTES represents a
      potent eosinophil-specific activator of oxidative metabolism. Besides its
      chemotactic activity on T cells and eosinophils, therefore, RANTES may be
      involved in the functional activation of eosinophils in the skin of patients with
      atopic dermatitis.

PMID- 7516401
TI  - Prostate specific antigen density: a method for differentiating prostate
      carcinoma from benign prostatic hypertrophy demonstrates ethnic variation.

PMID- 7516400
TI  - Hailey-Hailey disease is not allelic to Darier's disease.
AB  - Hailey-Hailey (Familial Benign Chronic Pemphigus) Disease is a rare autosomal
      dominant disorder characterized by blisters caused by suprabasal epidermal
      acantholysis. Another autosomal dominant skin disease, Darier's disease, has
      clinical and histologic features which overlap those of Hailey-Hailey disease and
      recently has been mapped to chromosome 12q23-q24.1. We have used linkage analysis
      to test whether or not a mutation in this region might also underlie Hailey
      Hailey disease. This analysis, using polymorphic loci tightly linked to Darier's
      disease, excluded this region as the site for the disease-causing mutation in two
      kindreds affected with Hailey-Hailey disease.

PMID- 7516402
TI  - Lymphoid and myeloid differentiation of fetal liver CD34+lineage- cells in human
      thymic organ culture.
AB  - In this article, we report that the human fetal thymus contains CD34bright cells
      (< 0.01% of total thymocytes) with a phenotype that resembles that of multipotent
      hematopoietic progenitors in the fetal bone marrow. CD34bright thymocytes were
      CD33-/dull and were negative for CD38, CD2, and CD5 as well as for the lineage
      markers CD3, CD4, and CD8 (T cells), CD19 and CD20 (B cells), CD56 (NK cells),
      glycophorin (erythrocytes), and CD14 (monocytes). In addition, total CD34+
      lineage negative (lin-) thymocytes contained a low number of primitive myeloid
      progenitor cells, thus suggesting that the different hematopoietic lineages
      present in the thymus may be derived from primitive hematopoietic progenitor
      cells seeding the thymus. To investigate whether the thymus is permissive for the
      development of non-T cells, human fetal organ culture (FTOC) assays were
      performed by microinjecting sorted CD34+lin- fetal liver cells into fragments of
      HLA-mismatched fetal thymus. Sequential phenotypic analysis of the FTOC-derived
      progeny of CD34+lin- cells indicated that the differentiation into T cells was
      preceded by a wave of myeloid differentiation into CD14+CD11b+CD4dull cells.
      Donor-derived B cells (CD19+CD20+) were also generated, which produced
      immunoglobulins (IgG and IgM) when cultured under appropriate conditions, as well
      as functional CD56+CD3- NK cells, which efficiently killed K562 target cells in
      cytotoxicity assays. These results demonstrate that the microinjection of fetal
      liver hematopoietic progenitors into fetal thymic organ fragments results in
      multilineage differentiation in vitro.

PMID- 7516403
TI  - A pathogenic autoimmune process targeted at a surrogate epitope.
AB  - Immunization with the retinal interphotoreceptor retinoid-binding protein (IRBP)
      induces in a variety of animals an inflammatory eye disease, experimental
      autoimmune uveoretinitis (EAU). We have previously shown that sequence 1181-1191
      of bovine IRBP (BOV 1181-1191) is immunodominant and highly uveitogenic and
      immunogenic in Lewis rats. Sequence 1181-1191 of the rat IRBP (RAT 1181-1191)
      differs from BOV 1181-1191 by two residues, at positions 1188 and 1190, that are
      pivotal for the immunological activity of the bovine epitope. Here we show that,
      unlike its bovine homologue, RAT 1181-1191 did not induce EAU or an immune
      response in Lewis rats. The immunological inactivity of RAT 1181-1191 in Lewis
      rats is due at least in part to its poor affinity toward the antigen-presenting
      cells of these rats, as shown by its failure to compete with binding of BOV 1181
      1191 to Lewis adherent spleen cells. Moreover, unlike all other known autologous
      homologues of immunopathogenic epitopes, RAT 1181-1191 was not recognized by
      lymphocytes sensitized against BOV 1181-1191 and failed to stimulate
      proliferation, uveitogenic capacity or signal transduction in these cells. These
      findings thus suggest that RAT 1181-1191 is not a likely target for lymphocytes
      sensitized against BOV 1181-1191 in the process in which these cells recognize
      IRBP in the rat eye and trigger the inflammatory reaction of EAU. Our data
      further suggest that the target for the disease-inducing lymphocytes is sequence
      273-283 of the rat IRBP: (a) sequence 273-283 is highly conserved and is
      identical in the bovine and rat proteins; (b) determinant 273-283 is a "repeat"
      of 1181-1191 in the fourfold structure of IRBP and shares seven residues with BOV
      1181-1191; (c) rat peptide 273-283 is recognized by lymphocytes sensitized
      against BOV 1181-1191 and stimulates them for proliferation and for acquisition
      of uveitogenicity; and (d) moreover, sequence 273-283 is superior to BOV 1181
      1191 in its capacity to generate uveitogenicity in lymphocytes sensitized against
      this bovine peptide. The present study thus describes for the first time a system
      in which an autologous homologue of an immunopathogenic epitope is inactive and a
      "surrogate" determinant apparently serves as the target for lymphocytes
      sensitized against the immunopathogenic peptide.

PMID- 7516405
TI  - gp39-CD40 interactions are essential for germinal center formation and the
      development of B cell memory.
AB  - gp39, the ligand for CD40 expressed on activated CD4+ T helper cells, is required
      for the generation of antibody responses to T-dependent (TD) antigens. Treatment
      of mice with anti-gp39 in vivo inhibits both primary and secondary antibody
      formation to TD, but not T-independent antigens. However, the role of this
      receptor-ligand pair in the development of germinal centers and the generation of
      B cell memory is as yet undefined. Using an antibody to gp39, this study examines
      the in vivo requirement for gp39-CD40 interactions in the induction of germinal
      center formation, as well as in the generation of B cell memory. Animals were
      immunized, treated in vivo with anti-gp39, and evaluated using
      immunohistochemical staining for the presence of splenic germinal centers 9-11 d
      after immunization. The results demonstrate that the formation of germinal
      centers was completely inhibited as a result of treatment with anti-gp39.
      Moreover, adoptive transfer experiments demonstrate that the generation of
      antigen-specific memory B cells is also inhibited as a consequence of blocking
      gp39-CD40 interactions. Taken together, the data demonstrate that gp39-CD40
      interactions are critical not only for the generation of antibody responses, but
      also in the development of B cell memory.

PMID- 7516404
TI  - Memory B cell development but not germinal center formation is impaired by in
      vivo blockade of CD40-CD40 ligand interaction.
AB  - To study the role of the CD40-CD40 ligand interaction in the development of
      memory B cells and its level of action during primary antibody responses in vivo,
      mice were injected with a soluble CD40 fusion protein (sCD40-gamma 1), so as to
      block the interaction. The effects of the treatment on the primary antibody
      response were reminiscent of hyper-immunoglobulin M (IgM) syndrome (HIMG1):
      antigen-specific IgG responses were grossly inhibited whereas the IgM response
      was augmented severalfold. The latter observation suggests that there is a T
      dependent, CD40 ligand-independent pathway of B cell activation that leads to IgM
      responses and that a significant component of the IgM in HIMG1 patients is
      derived from T-dependent responses. The secondary response was not readily
      blocked by sCD40-gamma 1 treatment, indicating a relative independence of CD40
      ligation of antigen-experienced B cells. The most striking finding from these
      studies is that the development of memory B cell populations (measured by
      adoptive transfer) is grossly impaired by administration of sCD40-gamma 1 during
      the early induction phase of the response. It is surprising that although the
      generation memory is diminished, there is no quantitative difference in the
      development of germinal centers. Whereas entry of B cells into the memory cell
      pathway is dependent on CD40 ligation, the clonal expansion of the potential
      memory precursors in germinal centers seems not to require a CD40 signal.

PMID- 7516406
TI  - CD19 has a potential CD77 (globotriaosyl ceramide)-binding site with sequence
      similarity to verotoxin B-subunits: implications of molecular mimicry for B cell
      adhesion and enterohemorrhagic Escherichia coli pathogenesis.
AB  - The glycosphingolipid globotriaosyl ceramide (CD77) and other globo-series
      glycolipids containing terminal galactose (Gal)alpha 1-4Gal residues function as
      receptors for the verotoxin (Shiga-like toxin) family of Escherichia coli
      elaborated toxins. CD77 is also a marker for germinal center B lymphocytes and
      Burkitt's lymphoma cells. The pan B cell marker CD19 is a 95-kD membrane protein
      that appears early in B cell differentiation and is only lost upon terminal
      differentiation to plasma cells. CD19 is involved in signal transduction and has
      a regulatory role in B cell proliferation and differentiation in response to
      activation in vitro. However, an endogenous ligand for CD19 has not yet been
      identified. We report herein that the extracellular domain of CD19 has a
      potential CD77-binding site with extensive sequence similarity to the verotoxin B
      subunits. These B-subunit-like sequences on CD19 are in close proximity following
      the organization of intervening amino acids into disulfide-linked domains.
      Cocapping of CD19 and CD77 on Burkitt's lymphoma-derived Daudi cells with anti
      CD19 antibodies indicates that CD19 and CD77 are associated on the B cell
      surface. Cell surface binding of anti-CD19 antibodies is decreased on CD77
      deficient mutant Daudi cells, suggesting that CD77 expression influences the
      surface expression of CD19. Wild-type Daudi cells, but not the CD19/CD77
      deficient mutants, bind to matrices expressing the carbohydrate moiety of CD77 or
      other Gal alpha 1-4Gal containing glycolipids. This binding can be inhibited by
      anti-CD77 antibodies, the CD77-binding verotoxin B-subunit or anti-CD19
      antibodies. Daudi cells exhibit a degree of spontaneous homotypic adhesion in
      culture while the CD77/CD19-deficient Daudi mutants grow as single cells. The
      stronger homotypic adhesion that occurs in B cells after antibody ligation of
      CD19 and that involves, to some extent, the integrin system, is also dramatically
      lower in the mutant cells relative to the parent cell line. However,
      reconstitution of mutant cells with CD77 restores the anti-CD19 mAb-induced
      adhesion to wild-type Daudi cell levels. These studies represent the first time
      that CD19-mediated signaling has been reconstituted in a low-responder B cell
      line. These convergent observations provide compelling evidence that CD19/CD77
      interactions function in adhesion and signal transduction at a specific stage in
      B cell development and suggest that such interactions have a role in B lymphocyte
      homing and germinal center formation in vivo. By targeting CD77+ B cells,
      verotoxins may suppress the humoral arm of the immune response during
      infection.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7516407
TI  - Serum amyloid A is a chemoattractant: induction of migration, adhesion, and
      tissue infiltration of monocytes and polymorphonuclear leukocytes.
AB  - Serum amyloid A (SAA) is an acute phase protein that in the blood is bound to
      high density lipoproteins; SAA is secreted mainly by hepatocytes, and its
      concentration increases in the blood up to 1000 times during an inflammatory
      response. At present, its biological function is unclear. Since some forms of
      secondary amyloidosis are caused by deposition in tissues of peptides derived
      from the SAA and leukocytes seem to be involved in this process, we investigated
      the effect of human SAA on human monocytes and polymorphonuclear cells (PMN).
      When recombinant human SAA (rSAA) was used at concentrations corresponding to
      those found during the acute phase (> 0.8 microM), it induced directional
      migration of monocytes and polymorphonuclear leukocytes. Preincubation of rSAA
      with high density lipoproteins blocked this chemoattractant activity for both
      monocytes and PMN. rSAA also regulated the expression of the adhesion proteins
      CD11b and leukocyte cell adhesion molecule 1 and induced the adhesion of PMN and
      monocytes to umbilical cord vein endothelial cell monolayers. When subcutaneously
      injected into mice, rSAA recruited PMN and monocytes at the injection site. On
      the basis of these data, we suggest that SAA may participate in enhancing the
      migration of monocytes and PMN to inflamed tissues during an acute phase
      response.

PMID- 7516408
TI  - Interleukin 12 synergizes with B7/CD28 interaction in inducing efficient
      proliferation and cytokine production of human T cells.
AB  - Several receptors and counter-receptor pairs on T cells and on antigen-presenting
      cells (APCs) deliver costimulatory signals to T cells during antigen
      presentation. The CD28 receptor on T cells with its ligand B7 represents one of
      the best characterized and most important examples of this costimulation. We show
      here that interleukin 12 (IL-12), a cytokine also produced by APCs
      (monocyte/macrophages and B cells) and active on T and natural killer cells, has
      a strong synergistic effect with the B7/CD28 interaction in inducing
      proliferation and cytokine production in both mitogen-activated and freshly
      isolated peripheral blood T cells. Together with anti-CD28 antibodies, IL-12
      induces proliferation of T cells to levels higher than those obtained with IL-2
      stimulation and it is effective at IL-12 concentrations 100- to 1,000-fold lower
      than effective concentrations of IL-2. The proliferative effect of anti-CD28 and
      IL-12 is resistant to moderate doses of cyclosporin A and is largely independent
      of endogenous IL-2, IL-12, in synergy with anti-CD28 or B7-transfected cells, is
      most effective in inducing interferon gamma (IFN-gamma) production, but
      production of tumor necrosis factor alpha and granulocyte/macrophage colony
      stimulating factor is also observed. IL-12-induced IFN-gamma production in
      peripheral blood mononuclear cells is inhibited by the chimeric molecule CTLA-4
      immunoglobulin, which prevents binding of CD28 to B7, suggesting that endogenous
      B7 on the mononuclear cells and IL-12 cooperate in inducing IFN-gamma production.
      IL-10 inhibits both IL-12 production and B7 expression on monocytes. These two
      effects are largely responsible for the ability of IL-10, acting on accessory
      cells, to inhibit IFN-gamma production by lymphocytes, because anti-CD28
      antibodies and IL-12 can reverse the inhibitory effect of IL-10 on IFN-gamma
      production. Our results in vitro suggest that the synergy between B7 and IL-12, a
      surface antigen and a soluble product of APCs, respectively, plays a role in
      regulating T cell activation and immune response in the microenvironment of
      inflamed tissues.

PMID- 7516409
TI  - B7 and interleukin 12 cooperate for proliferation and interferon gamma production
      by mouse T helper clones that are unresponsive to B7 costimulation.
AB  - We have previously shown that dendritic cells isolated after overnight culture,
      which can express B7 and are potent stimulators of naive T cell proliferation,
      are relatively poor at inducing the proliferation of a panel of murine T helper 1
      (Th1) clones. Maximal stimulation of Th1 clones was achieved using unseparated
      splenic antigen presenting cells (APC). An explanation for these findings is
      provided in the present study where we show that FcR+ L cells transfected with B7
      stimulate minimal proliferation of Th1 clones in response to anti-CD3 antibodies,
      in contrast to induction of significant proliferation of naive T cells. However,
      addition of interleukin 12 (IL-12) to cultures of Th1 cells stimulated with anti
      CD3 and FcR+ B7 transfectants resulted in a very pronounced increase in
      proliferation and interferon gamma (IFN-gamma) production. Exogenous IL-12 did
      not affect the B7-induced proliferation of naive T cells. This showed that
      whereas costimulatory signals delivered via B7-CD28 interaction are sufficient to
      induce significant proliferation of naive T cells activated through occupancy of
      the T cell receptor, Th1 T cell clones require cooperative costimulation by B7
      and IL-12. This costimulation was shown to be specific by inhibition of
      proliferation and IFN-gamma production using chimeric soluble cytolytic T
      lymphocyte-associated antigen 4-human IgG1Fc (CTLA4-Ig) and anti-IL-12
      antibodies. Furthermore, the significant antigen specific proliferation and IFN
      gamma production by Th1 clones observed when splenocytes were used as APC was
      almost completely abrogated using CTLA4-Ig and anti-IL-12 antibodies. Thus two
      costimulatory signals, B7 and IL-12, account for the ability of splenic APC to
      induce maximal stimulation of Th1 clones. IL-10 downregulates the expression of
      IL-12 by IFN-gamma-stimulated macrophages and this may account largely for t the
      ability of IL-10 to inhibit APC function of splenic and macrophage APC for the
      induction of Th1 cell proliferation and IFN-gamma production. Indeed we show that
      IL-12 can overcome the inhibitory effect of IL-10 for the APC-dependent induction
      of proliferation and IFN-gamma production by Th1 clones. These results suggest
      that proliferation by terminally differentiated Th1 clones, in contrast to naive
      T cells, requires stimulation via membrane-bound B7 and a cytokine, IL-12. It is
      possible that these signals may result in the activation of unresponsive T cells
      during an inflammatory response. IL-10, by its role in regulating such innate
      inflammatory responses, may thus help to maintain these T cells in an
      unresponsive state.

PMID- 7516411
TI  - Identification of the immunodominant peptides of the MART-1 human melanoma
      antigen recognized by the majority of HLA-A2-restricted tumor infiltrating
      lymphocytes.
AB  - Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase-related protein
      1 (gp75) were evaluated for recognition by HLA-A2-restricted melanoma-specific
      cytotoxic T lymphocytes (CTLs) derived from the tumor-infiltrating lymphocytes
      (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100
      (including 3 that also recognized MART-1), but none of the TIL recognized
      tyrosinase or gp75. Based on the known HLA-A2.1 peptide binding motifs, 23
      peptides from MART-1 were synthesized in an attempt to identify the epitopes
      recognized by TIL. Three peptides were recognized by TIL when pulsed on T2 target
      cells. One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing
      the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2
      restricted melanoma-specific CTLs. Therefore, this peptide appears to be a very
      common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be
      useful for the development of immunotherapeutic strategies.

PMID- 7516410
TI  - PUVA bath therapy strongly suppresses immunological and epidermal activation in
      psoriasis: a possible cellular basis for remittive therapy.
AB  - Psoriasis is characterized by alterations in both the epidermis and dermis of the
      skin. Epidermal keratinocytes display marked proliferative activation and
      differentiate along an "alternate" or "regenerative" pathway, while the dermis
      becomes infiltrated with leukocytes, particularly interleukin 2 (IL-2) receptor
      bearing "activated" T cells. Psoralens, administered by the oral route, have
      therapeutic effects in psoriasis when photochemically activated by ultraviolet A
      light (PUVA therapy). Recently psoralen bath therapy has been introduced to more
      effectively deliver this agent to the diseased skin. We have correlated the
      efficacy of PUVA bath therapy with its effects on specific molecular and cellular
      parameters of disease, in 10 consecutive patients with recalcitrant psoriasis.
      Rapid clearing of lesions occurred in 8 out of 10 patients. Biopsies were taken
      from lesional and nonlesional skin before and after a single round of therapy,
      and observation was continued in our Clinical Research Center at The Rockefeller
      University. Enumeration of cycling keratinocytes with the Ki-67 monoclonal
      antibody showed that PUVA reduced cell proliferation by 73%. The pathological
      increase in insulin-like growth factor 1 (IGF-1) receptors was reversed, whereas
      epidermal growth factor (EGF) receptors, which are also increased in psoriasis,
      remained unchanged. Keratinocyte proteins that are expressed in abnormal sites of
      the epidermis during psoriasis, i.e., keratin 16, filaggrin, and involucrin,
      were, after PUVA treatment, localized to their normal sites. Epidermal and dermal
      T-lymphocytes (CD3+), as well as CD4+, CD8+, and IL-2 receptor+ subsets, were
      strongly suppressed by PUVA, with virtual elimination of IL-2 receptor+ T cells
      in some patients. Consistent with diminished lymphocyte activation, HLA-DR
      expression by epidermal keratinocytes was markedly reduced in treated skin. In
      comparison to cyclosporine treatment of psoriasis, PUVA therapy leads to more
      complete reversal of pathological epidermal and lymphocytic activation, changes
      which we propose to be the cellular basis for a more sustained remission of
      disease after PUVA treatment.

PMID- 7516412
TI  - Induction of nitric oxide synthase protects against malaria in mice exposed to
      irradiated Plasmodium berghei infected mosquitoes: involvement of interferon
      gamma and CD8+ T cells.
AB  - Exposure of BALB/c mice to mosquitoes infected with irradiated Plasmodium berghei
      confers protective immunity against subsequent sporozoite challenge. Immunized
      mice challenged with viable sporozoites develop parasitemia when treated orally
      with substrate inhibitors of nitric oxide synthase (NOS). This suggests that the
      production of nitric oxide (NO) prevents the development of exoerythrocytic
      stages of malaria in liver. Liver tissue from immunized mice expressed maximal
      levels of mRNA for inducible NOS (iNOS) between 12 and 24 h after challenge with
      sporozoites. Intraperitoneal injection of neutralizing monoclonal antibody
      against interferon gamma (IFN-gamma) or in vivo depletion of CD8+ T cells, but
      not CD4+ T cells, at the time of challenge blocked expression of iNOS mRNA and
      ablated protection in immunized mice. These results show that both CD8+ T cells
      and IFN-gamma are important components in the regulation of iNOS in liver which
      contributes to the protective response of mice immunized with irradiated malaria
      sporozoites. IFN-gamma, likely provided by malaria-specific CD8+ T cells, induces
      liver cells, hepatocytes and/or Kupffer cells, to produce NO for the destruction
      of infected hepatocytes or the parasite within these cells.

PMID- 7516414
TI  - Tumor necrosis factor alpha-induced angiogenesis depends on in situ platelet
      activating factor biosynthesis.
AB  - Tumor necrosis factor (TNF) alpha, a potent inhibitor of endothelial cell growth
      in vitro, is angiogenic in vivo. Therefore, it was suggested that the angiogenic
      properties of this agent might be consequent to the production of secondary
      mediators. Since TNF-alpha stimulates the synthesis of platelet-activating factor
      (PAF) by monocytes and endothelial cells, we investigated the possible
      involvement of PAF in the angiogenic effect of TNF-alpha. Angiogenesis was
      studied in a murine model in which Matrigel was used as a vehicle for the
      delivery of mediators. In this model the angiogenesis induced by TNF-alpha was
      shown to be inhibited by WEB 2170, a specific PAF receptor antagonist. Moreover,
      in mice injected with TNF-alpha, PAF was detected within the Matrigel, 6 and 24 h
      after TNF-alpha injection. The synthesis of PAF within the Matrigel was
      concomitant with the early migration of endothelial cells and infiltration of
      monocytes. No infiltration of lymphocytes or polymorphonuclear leukocytes was
      observed. Synthetic PAF as well as PAF extracted and purified from mice
      challenged with TNF-alpha induced a rapid angiogenic response, inhibited by WEB
      2170. These results suggest that the angiogenic effect of TNF-alpha is, at least
      in part, mediated by PAF synthesized from monocytes and/or endothelial cells
      infiltrating the Matrigel plug.

PMID- 7516413
TI  - Eosinophil adhesion to nasal polyp endothelium is P-selectin-dependent.
AB  - Tissue eosinophilia is a characteristic feature of a number of inflammatory
      diseases including asthma and nasal polyposis. Eosinophil migration into tissues
      is controlled in part by interactions between eosinophil adhesion receptors and
      counter-structures on the vascular endothelium. To determine the receptors used
      by eosinophils to adhere to vascular endothelium in allergic inflammation we have
      adapted the Stamper-Woodruff frozen section assay (FSA) to study eosinophil
      adhesion to nasal polyp endothelium. Immunohistology indicated that intercellular
      adhesion molecule 1 (ICAM-1), E-selectin and P-selectin were well expressed by
      nasal polyp endothelium, whereas expression of vascular cell adhesion molecule 1
      (VCAM-1) was weak or absent. Unstimulated human peripheral blood eosinophils
      adhered specifically to nasal polyp endothelium. Adherence was temperature and
      divalent cation-dependent and saturable at cell densities > 5 x 10(6) cells/ml.
      Eosinophil adhesion was almost completely inhibited by a monoclonal antibody
      (mAb) against P-selectin and by a chimeric molecule consisting of the Fc portion
      of human IgG and the lectin binding domain of P-selectin, which binds to the P
      selectin ligand on leucocytes. Anti-Mac-1 mAb partially inhibited eosinophil
      adhesion whereas mAb against E-selectin, L-selectin, ICAM-1, VCAM-1, very late
      activation antigen 4, and lymphocyte function-associated antigen 1 had no effect.
      P-selectin is stored in intracellular granules within the endothelial cell and in
      vitro is only transiently expressed. To determine if P-selectin was expressed on
      the membrane of the nasal polyp endothelium we compared P-selectin expression in
      normal skin and nasal polyps after acetone fixation, which permeabilizes cells,
      and paraformaldehyde, which only allows staining of membrane expressed receptors.
      In the skin, good expression was seen with acetone fixation but no expression was
      seen after paraformaldehyde treatment, whereas in nasal polyps, similar
      expression was observed with both fixatives. In addition immunofluorescence with
      confocal microscopy demonstrated lumenal staining of nasal polyp endothelium
      indicating that P-selectin was located on the surface of endothelial cells while
      in skin only an intracellular granular distribution was apparent. Lastly, whereas
      eosinophils bound consistently to nasal polyp endothelium, no binding was
      observed to blood vessels in normal skin further supporting the idea that
      eosinophils were binding to membrane expressed and not intracellular P-selectin.
      The importance of P-selectin in eosinophil adhesion to nasal polyp endothelium
      suggests that P-selectin antagonists may be effective at inhibiting eosinophil
      accumulation at sites of allergic inflammation.

PMID- 7516415
TI  - Hyaluronan binding function of CD44 is transiently activated on T cells during an
      in vivo immune response.
AB  - Though CD44 functions as a cell surface receptor for hyaluronan (HA) in some cell
      lines, most normal hematopoietic cells expressing CD44 do not bind HA. Certain
      CD44-specific monoclonal antibodies (mAbs) can rapidly induce CD44-mediated HA
      binding in normal murine T cells. This observation suggests that in vivo
      mechanisms may exist for activating the HA receptor function of CD44 on normal T
      cells. Here, it is shown that up to one third of splenic T cells are capable of
      CD44-mediated binding of fluorescein-conjugated HA (Fl-HA) during an in vivo
      allogeneic response. HA binding activity peaks at 7-8 d postinjection and
      declines rapidly. These rapid kinetics could be the result of transient
      activation of CD44 function and/or differentiation or expansion of short-lived
      population(s) that have constitutive HA-binding function. Both CD4 and CD8 T
      cells are included in the HA binding population which is strongly CD44 positive.
      After separation of HA-binding cells from nonbinding cells by cell sorting, it is
      shown that almost all cytotoxic effector cells are found in the HA-binding
      population. However, there is no evidence that CD44-mediated HA recognition is
      directly involved in the killing of target cells, since cytotoxicity could not be
      inhibited by CD44-specific mAbs that inhibit HA binding or by soluble HA. PCR
      amplification of cDNA reverse transcribed from RNA of sorted HA-binding cells
      indicated no evidence for CD44 isoforms other than the standard (hematopoietic)
      form. Though CD44 expression is known to be elevated upon T cell activation, and,
      as shown here, HA-binding function is induced in a portion of CD44-expressing T
      cells including cytotoxic effector cells, the role of CD44 and HA-recognition in
      immune responses is not known.

PMID- 7516416
TI  - Antibodies inhibit the protease-mediated processing of a malaria merozoite
      surface protein.
AB  - When merozoites of the malaria parasite Plasmodium falciparum are released from
      infected erythrocytes and invade new red cells, a component of a protein complex
      derived from the merozoite surface protein 1 (MSP-1) precursor undergoes a single
      proteolytic cleavage known as secondary processing. This releases the complex
      from the parasite surface, except for a small membrane-bound fragment consisting
      of two epidermal growth factor (EGF)-like domains, which is the only part of MSP
      1 to be carried into invaded erythrocytes. We report that, a group of monoclonal
      antibodies specific for epitopes within the EGF-like domains, some interfere with
      secondary processing whereas others do not. Those that most effectively inhibit
      processing have previously been shown to prevent invasion. Other antibodies, some
      of which can block this inhibition, not only do not prevent invasion but are
      carried into the host cell bound to the merozoite surface. These observations
      unequivocally demonstrate that the binding of antibody to the COOH-terminal
      region of MSP-1 on the merozoite surface may not be sufficient to prevent
      erythrocyte invasion, and show that the interaction of different antibodies with
      adjacent epitopes within the EGF-like domains of MSP-1 can have distinct
      biochemical effects on the molecule. Inhibition of MSP-1 processing on merozoites
      may be a mechanism by which protective antibodies interrupt the asexual cycle of
      the malaria parasite.

PMID- 7516419
TI  - Detection of the negative strand of hepatitis E virus RNA in the livers of
      experimentally infected rhesus monkeys: evidence for viral replication.
AB  - Hepatitis E virus (HEV), the causative agent of enteric non-A, non-B hepatitis,
      is a positive-stranded RNA virus. Because of the virus's inability to grow in
      culture, several nonhuman primates have been used for the propagation of HEV.
      Using strand-specific reverse transcription-polymerase chain reaction (RT-PCR),
      we demonstrate the presence of negative-stranded HEV RNA replicative
      intermediates in the livers of infected animals. This constitutes the first
      direct evidence of HEV replication in the liver of the infected animals and
      reinforces the validity of such a model to study HEV infection, disease
      pathogenesis, and immunity.

PMID- 7516418
TI  - Interleukin 13: novel role in direct regulation of proliferation and
      differentiation of primitive hematopoietic progenitor cells.
AB  - The recently cloned interleukin 13 (IL-13) shares most investigated biological
      activities on B lymphocytes and monocytes with IL-4. In this study we
      investigated for the first time the potential role of IL-13 in the regulation of
      the growth of hematopoietic progenitor cells. IL-13 enhanced stem cell factor
      (SCF)-induced proliferation of Lin-Sca-1+ bone marrow progenitor cells more
      potently than IL-4. The effect of IL-13 was purely synergistic, since IL-13 alone
      stimulated no colony formation. Single cell experiments suggested that the
      synergistic effect of IL-13 on Lin-Sca-1+ progenitors was directly mediated. In
      contrast, IL-13 had no synergistic activity on SCF-induced proliferation of the
      more mature Lin-Sca-1- progenitor cells. Thus, the cloning frequency in response
      to SCF + IL-13 was at least 20-fold higher in the Lin-Sca-1+ than the Lin-Sca-1-
      progenitor cell population. Furthermore, IL-13 but not IL-4 synergistically
      enhanced colony formation of Lin-Sca-1+ progenitors in response to
      granulocyte/macrophage colony-stimulating factor (GM-CSF) (threefold), whereas
      both IL-4 and IL-13 enhanced G-CSF-induced colony formation (threefold), and
      neither of the two significantly affected CSF-1 and IL-3-induced proliferation.
      Finally, whereas stimulation of Lin-Sca-1+ progenitors by SCF + G-CSF resulted in
      the formation of 90% granulocytes, the addition of IL-13 resulted in the
      production of macrophages exclusively. This novel effect on differentiation was
      directly mediated, shared with IL-4, and could not be observed on Lin-Sca-1-
      progenitor cells. Collectively, these findings indicate a novel role of IL-13 in
      early myelopoiesis, partially overlapping but also different from that of IL-4.

PMID- 7516417
TI  - Interaction between CD44 and hyaluronate is directly implicated in the regulation
      of tumor development.
AB  - CD44 is implicated in the regulation of tumor growth and metastasis but the
      mechanism by which expression of different CD44 isoforms determines the rate of
      primary and secondary tumor growth remains unclear. In the present study we use a
      human melanoma transfected with wild-type and mutant forms of CD44 to determine
      which functional property of the CD44 molecule is critical in influencing tumor
      behavior. We show that expression of a wild-type CD44 isoform that binds
      hyaluronic acid augments the rapidity of tumor formation by melanoma cells in
      vivo, whereas expression of a CD44 mutant, which does not mediate cell attachment
      to hyaluronate, fails to do so. The importance of CD44-hyaluronate interaction in
      tumor development is underscored by the differential inhibitory effect of soluble
      wild-type and mutant CD44-Ig fusion proteins on melanoma growth in vivo. Whereas
      local administration of a mutant, nonhyaluronate binding, CD44-Ig fusion protein
      has no effect on subcutaneous melanoma growth in mice, infusion of wild-type CD44
      Ig is shown to block tumor development. Taken together, these observations
      suggest that the tumor growth promoting property of CD44 is largely dependent on
      its ability to mediate cell attachment to hyaluronate.

PMID- 7516420
TI  - Detection of hepatitis C virus RNA genome in liver tissue by nonisotopic in situ
      hybridization.
AB  - A rapid technique for the detection of hepatitis C virus (HCV) RNA in liver
      section using nonisotopic in situ hybridization was described. Only 3 of the 10
      patients seropositive for antibody to HCV and HCV RNA had detectable HCV RNA in
      the hepatocytes (1%, 2%, and 15% of cells positive). No specific signal was
      detected in sinusoidal, biliary epithelial, and mononuclear cells. The positive
      hepatocytes were scattered in the liver lobule with occasional clusters. The
      positive signal was confined to the cytoplasmic compartment. These data support
      the previous observation of the hepatocyte tropism of HCV.

PMID- 7516421
TI  - Hepatitis C virus-RNAs in plasma and in peripheral blood mononuclear cells of
      hemophiliacs with chronic hepatitis C: evidence for viral replication in
      peripheral blood mononuclear cells.
AB  - Hemophiliacs who have been exposed to unheated and/or dry heated pooled clotting
      factor concentrates are at high risk of chronic hepatitis C. Although the
      mechanism and site of hepatitis C virus (HCV) replication are not yet known, HCV
      is thought to replicate through a complementary negative RNA strand, as has been
      shown for flaviviruses. The detection of negative RNA strands has therefore been
      regarded as a marker of replication. We investigated the prevalence of HCV-RNA
      and of negative HCV-RNA strands in peripheral blood mononuclear cells (PBMC) and
      plasma of hemophiliacs. Forty-three of 47 patients studied (91%) had anti-HCV
      antibodies and in 36 patients HCV-RNA was detectable in PBMC. In one group of 20
      patients negative HCV-RNA strands were present in PBMC and 10 of these patients
      also had negative HCV-RNA strands in plasma. In another group of nine patients
      HCV-RNA was detected in PBMC, although cDNA synthesis was carried out in the
      absence of primers. Only in two of these nine patients negative and positive HCV
      RNA strands were demonstrated specifically in PBMC using a modified reverse
      transcription step. If the presence of negative HCV-RNA strands can be considered
      as marker of viral replication, the findings indicate that HCV can replicate in
      PBMC. Furthermore, in certain patients it is impossible to use the currently
      available technique to detect selectively positive or negative HCV-RNA strands.

PMID- 7516424
TI  - Cerebrospinal fluid cytology in granulocytic sarcoma with meningeal extension but
      without bone marrow involvement.
AB  - Granulocytic sarcoma (GS) is a localized tumour of immature granulocytes that is
      usually associated with myelogenous leukaemia. We report an unusual case of
      mastoid GS with meningeal extension but no bone marrow involvement on
      presentation. Histological examination of the surgical specimen and the
      characteristic cerebrospinal fluid (CSF) cytology showing cytoplasmic
      granulations and Auer bodies led to the diagnosis of GS. Positive cytochemical
      staining of the immature CSF cells for naphthol-ASD chloroacetate esterase and
      myeloperoxidase confirmed their myeloid origin. Immunophenotyping did not reveal
      common acute lymphoblastic leukaemia antigen, cytokeratin, T- or B-cell antigens.
      The patient underwent surgical resection of the localized tumour, followed by
      radiation therapy, intrathecal and systemic chemotherapy, as if he had acute
      myelogenous leukaemia (AML). He did not develop AML in the 21 months after the
      tumour resection. This case emphasizes the value of CSF cytological examination
      of tumour cells and the use of an immunocytochemical marker for differentiating
      GS from malignant lymphoma.

PMID- 7516422
TI  - Genotypes and titers of hepatitis C virus for predicting response to interferon
      in patients with chronic hepatitis C.
AB  - Interferon induces remission in about 50% of patients with chronic hepatitis C,
      but it is difficult to predict which patients will respond. Host and viral
      factors were evaluated for correlation with response to interferon in patients
      with chronic hepatitis C. Recombinant interferon alpha-2b with a total dose of
      480-560 million units was given to 136 patients, of whom 74 (54%) responded.
      Genotypes of hepatitis C virus (HCV) in sera, I, II, III, IV, and V, were
      determined by polymerase chain reaction (PCR) with type-specific primers. In 72
      patients, pretreatment levels of HCV RNA were titrated by PCR in serial tenfold
      dilutions of RNA extracted from serum. Response to interferon occurred in 34
      (40%) of 85 patients infected with HCV of genotype II, less frequently than in 22
      (85%) of 26 with genotype III (P < 0.001) or in 7 (70%) of 10 with genotype IV.
      Of 51 patients with genotype II HCV, 6 of 8 (75%) with HCV RNA titers < 10(6)
      responded, more frequently than 4 of 43 (9%) with titers > or = 10(6) (P <
      0.001). Responders were younger than non-responders (45.7 +/- 11.7 vs. 50.3 +/-
      9.6 yr) and had received transfusions less frequently (26/74 or 35% vs. 37/62 or
      60%, P < 0.01). Response to interferon correlated inversely with the severity of
      liver histopathology. These results indicate that response to interferon is
      influenced by HCV genotypes and pretreatment levels of HCV RNA in serum.

PMID- 7516423
TI  - IgM antibody to a hepatitis C virus core peptide (CP14) for monitoring activity
      of liver disease in patients with acute or chronic hepatitis C.
AB  - Antibodies to the hepatitis C virus (HCV) core of various immunoglobulin classes
      were determined by enzyme immunoassays with three synthetic peptides, CP14 (amino
      acids 5-40 of the core protein), CP10 (5-23), and CP9 (39-74). In 135 patients
      with chronic type C liver disease, anti-CP14, anti-CP10, and anti-CP9 of IgG
      class were detected in 99%, 94%, 82%, respectively; those of IgM class in 86%,
      69%, and 39%; and those of IgA class in 56%, 40%, and 4%. Thus anti-CP14 was more
      prevalent than anti-CP10 or anti-CP9 in every immunoglobulin class. The
      prevalence of IgM anti-CP14 was much higher (P < 0.001) in patients (116/135 or
      86%) than in asymptomatic carriers of HCV (13/39 or 33%). In seven patients with
      acute hepatitis C, IgM anti-CP14 continued to decrease in two in whom hepatitis
      resolved, but increased in five in whom hepatitis once resolved and then
      exacerbated. IgM anti-CP14 was followed in 30 patients with chronic hepatitis C
      during 24 weeks while they received recombinant interferon alpha-2a. IgM anti
      CP14 decreased remarkably within 8 weeks in all of them. Thereafter, it continued
      to decrease in nine patients who responded to interferon and lost HCV RNA from
      circulation, but started to increase in five non-responders who continued to have
      high titers of HCV RNA. In the remaining 16 patients in whom HCV RNA decreased
      once and then increased, IgM anti-CP14 continued to decrease till 20 weeks and
      then increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516425
TI  - Gene expression of cellular retinol-binding protein I (CRBP I) is affected by
      dietary proteins in the rat liver.
AB  - The effect of dietary proteins and vitamin A status on the gene expression of
      cellular retinol-binding protein I (CRBP I) was studied in the rat liver. The
      gene expression was estimated as amounts of transcript (mRNA) by Northern blot
      analysis using rat CRBP I cDNA. Though vitamin A status is known to positively
      regulate the gene expression of CRBP I in the extrahepatic tissues, in the
      present study we observed that the amount of the CRBP I transcript in liver was
      neither reduced by vitamin A-deficiency, nor affected by replenishment with an
      excess dose of all-trans retinoic acid. These results indicate that in the liver,
      different from the extrahepatic tissues, the gene expression of CRBP I may not be
      controlled by vitamin A. However, when the rats were fed on the diets that
      differed in dietary proteins, the gene expression of CRBP I in liver was enhanced
      by higher quality and quantity of dietary proteins, though no effect of dietary
      proteins was observed upon the hepatic contents of retinol. The concentrations of
      serum retinol were almost proportional to the mRNA levels of CRBP I. In contrast,
      the hepatic gene expression of another retinol-binding protein, RBP, and one
      subtype of retinoic acid receptor, RAR alpha was not influenced in the
      nutritional condition tested here. Our findings suggest that the gene expression
      of CRBP I in liver may be under control of the intake of dietary proteins. Thus,
      it is likely that in the light of the function of CRBP I on cellular transport
      and metabolism of retinol, dietary proteins may affect the actions of vitamin A
      in the extrahepatic tissues through changing the amounts of CRBP I in liver.

PMID- 7516426
TI  - Effects of diethylenetriamine and Aerosol OT on the stability of oil-in-water
      emulsion stabilized by interfacial polyurea film.
AB  - The stability of oil-in-water emulsions containing a triisocyanate soluble in the
      oil phase and an amine in the water phase was investigated. The oil component was
      di-n-butyl phthalate (DBP) containing Aerosol OT as an emulsifier. The time
      required for the average size parameter to reach a constant value was studied. It
      was found that the polyurea film produced by an interfacial polymerization
      reaction between the amine and the triisocyanate contributed to forming a stable
      emulsion at a lower Aerosol OT concentration, but at a higher Aerosol OT
      concentration the amine did not show any effect on the emulsion stability.

PMID- 7516428
TI  - Effects of heparin on excitation-contraction coupling in skeletal muscle toad and
      rat.
AB  - 1. Intracellularly applied heparin was found to cause a novel, use-dependent
      block of excitation-contraction (E-C) coupling in skinned skeletal muscle fibres
      of the toad. After one to four depolarizations in the presence of 100 micrograms
      ml-1 heparin, no further depolarization-induced responses could be elicited, even
      though addition of caffeine or lowering [Mg2+] could still induce massive Ca2+
      release. This effect could not be reversed by extensive wash-out of the heparin
      (> 15 min). 2. Heparin (100 micrograms ml-1) did not abolish subsequent
      depolarization-induced responses if applied while the voltage sensors were in
      either their resting or inactivated states, that is (a) while a fibre remained
      fully polarized, (b) when a fibre was already chronically depolarized or (c)
      after a fibre had been depolarized in the presence of D600 (gallopamil) and then
      repolarized. 3. When a toad fibre was depolarized in heparin, with the associated
      Ca2+ release blocked by the presence of 10 mM intracellular Mg2+, subsequent E-C
      coupling was abolished. Heparin did not interrupt E-C coupling when Ca2+ release
      was triggered in the absence of any depolarization, by either caffeine or low
      [Mg2+]. Thus, the opening of the Ca2+ release channels was neither necessary nor
      sufficient for heparin to abolish E-C coupling. 4. Heparin had direct effects on
      the contractile apparatus in toad fibres, increasing the Ca2+ sensitivity and
      decreasing the maximum Ca(2+)-activated force. These effects could only be partly
      reversed by extensive wash-out of heparin. 5. At 100 micrograms ml-1, both low
      molecular weight heparin and pentosanpolysulphate, another highly sulphated
      polysaccharide, were less effective than heparin in blocking the depolarization
      induced response and in changing the properties of the contractile apparatus, and
      these effects could be substantially reversed by wash-out. Two other polyanions,
      de-N-sulphated heparin (100 micrograms ml-1), which lacked N-sulphate groups, and
      polyglutamate (500 micrograms ml-1), had no measurable effect on either E-C
      coupling or the contractile apparatus. 6. In skinned fibres of the extensor
      digitorum longus muscle of the rat, 100 micrograms ml-1 heparin had little or no
      effect on E-C coupling and on the Ca2+ sensitivity of the contractile apparatus,
      but caused a larger reduction of the maximum Ca(2+)-activated force than in
      skinned fibres of the toad. 7. These results indicate that heparin blocks E-C
      coupling in toad muscle if, and only if, it is present when the voltage sensors
      are activated by depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7516427
TI  - Gating, selectivity and blockage of single channels activated by cyclic GMP in
      retinal rods of the tiger salamander.
AB  - 1. Patches in the inside-out configuration were excised from the membrane of
      outer and inner segments of the larval tiger salamander, Ambystoma tigrinum. The
      current flowing through single channels opened by cyclic GMP was studied with the
      voltage clamp technique. 2. Amplitude histograms of current recordings from
      patches containing only one flickering channel, excised from the inner segment
      and in the presence of 100 microM cyclic GMP, could be fitted by a theoretical
      scheme in which the single channel conductance was at least 55 pS at +40 mV and
      at least 45 pS at -40 mV. The mean open time was no longer than the time constant
      of our recording system, about 35 microseconds. Similar results were obtained by
      analysis of the amplitude histograms of patches from the outer segment containing
      many channels, and in the presence of 1-5 microM cyclic GMP. 3. In membrane
      patches excised from the outer segment, reducing the temperature from 24 to 8
      degrees C did not reduce the flickering, but changed the amplitude histograms of
      current fluctuations activated by 1 microM cyclic GMP in a way consistent with a
      decrease of 50% in the single channel conductance and a decrease of 50% in the
      open probability. 4. In the presence of 1 microM cyclic GMP at +60 mV, when Na+
      was replaced by NH4+ or K+, brief outward current transients flowing through
      single channels were observed. When Na+ was replaced with Li+, Rb+ or Cs+,
      current transients were very small. 5. The shape of the power spectrum of current
      fluctuations induced by 1 microM cyclic GMP at +60 mV did not change when the
      permeating ion was Na+, K+ or NH4+. Analysis of the amplitude histogram did not
      show any effect of the tested monovalent cations on the open probability or on
      channel gating. At +60 mV, the estimated single channel currents were at least 4,
      2.8 and 2 pA for NH4+, Na+ and K+ respectively. 6. The addition of 0.5 or 1 mM
      Ca2+ to the medium bathing the cytoplasmic side of the membrane greatly reduced
      the frequency of openings, but single channel activity could still be observed.
      The blocking effect of 1 mM Ca2+ on the channel activity induced by 2 microM
      cyclic GMP could be counterbalanced by increasing the cyclic GMP concentration.
      The addition of 0.5 or 1 mM Ca2+ did not change the shape of power spectra
      obtained at membrane voltages between -100 and +100 mV.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7516429
TI  - Seropositive versus seronegative rheumatoid arthritis--time for a new definition.

PMID- 7516430
TI  - Interrelationship of outcome measures and process variables in early rheumatoid
      arthritis. A comparison of radiologic damage, physical disability, joint counts,
      and acute phase reactants.
AB  - OBJECTIVE: To investigate the relationship between different outcome and process
      measures in early rheumatoid arthritis (RA). METHODS: A 3-year prospective study
      of 149 patients with early RA (symptoms < 1 year at entry). Results of serial
      measurements of process variables were transformed into time integrated values
      for comparison with the outcome measures. RESULTS: A highly significant
      correlation was found between the acute phase response, swollen joints, and
      radiological progression whereas none of these measures correlated with joint
      tenderness. Physical disability as estimated by the Health Assessment
      Questionnaire (HAQ) however, appeared to be determined by joint tenderness rather
      than by joint swelling. CONCLUSION: In early RA, joint swelling and acute phase
      reactants appear to be the most appropriate process variables for the prediction
      of radiological outcome, whereas joint tenderness is a strong determinant of
      physical disability (HAQ).

PMID- 7516431
TI  - Anticytoskeletal autoantibody development in adjuvant arthritis.
AB  - OBJECTIVE: Because the presence of autoantibodies against cell components is a
      common feature of most autoimmune diseases and some of these autoantibodies have
      been detected in sera of patients with rheumatic diseases such as rheumatoid
      arthritis (RA), we studied the presence of autoantibodies to cell components in
      an experimental model of chronic inflammation in rats, adjuvant arthritis (AA),
      to determine possible similarities between AA and human RA. METHODS: Sera from
      arthritic rats were initially tested by indirect immunofluorescence using rat
      liver sections as a substrate. Afterwards, arthritis sera were further studied in
      cultures of human skin fibroblasts and the HEp-2 cell line, with or without
      colchicine treatment. RESULTS: Results using liver as substrate showed that 31%
      of the arthritic rats showed a cytoskeleton staining pattern throughout the
      cytoplasm, with higher intensity of staining along the surface membranes,
      particularly in pericanalicular regions. This staining was suggestive of
      intermediate filament autoantibodies. When sera were analyzed on cultured cells,
      the results showed that the pattern is identical to the arrangement described for
      intermediate filaments and different from those seen with antiactin antibodies.
      Colchicine pretreatments ruled out antitubulin activity. Further analysis by
      immunoblotting revealed that autoantibodies did not recognize intermediate
      filament proteins when these were denatured in the electrophoretic process.
      CONCLUSION: The development of autoantibodies to intermediate filament proteins,
      both cytokeratin and vimentin, has been demonstrated in sera from rats with AA,
      in a similar manner to that described in human RA.

PMID- 7516432
TI  - Structure-function relationships in diphtheria toxin channels: I. Determining a
      minimal channel-forming domain.
AB  - Diphtheria Toxin (DT) is a 535 amino acid exotoxin, whose active form consists of
      two polypeptide chains linked by an interchain disulphide bond. DT's N-terminal A
      fragment kills cells by enzymatically inactivating their protein synthetic
      machinery; its C-terminal B chain is required for the binding of toxin to
      sensitive cells and for the translocation of the A fragment into the cytosol.
      This B fragment, consisting of its N-terminal T domain (amino acids 191-386) and
      its C-terminal R domain (amino acids 387-535) is responsible for the ion
      conducting channels formed by DT in lipid bilayers and cellular plasma membranes.
      To further delineate the channel-forming region of DT, we studied channels formed
      by deletion mutants of DT in lipid bilayer membranes under several pH conditions.
      Channels formed by mutants containing only the T domain (i.e., lacking the A
      fragment and/or the R domain), as well as those formed by mutants replacing the R
      domain with Interleukin-2 (IL-2), have single channel conductances and
      selectivities essentially identical to those of channels formed by wild-type DT.
      Furthermore, deleting the N-terminal 118 amino acids of the T domain also has
      minimal effect on the single channel conductance and selectivity of the mutant
      channels. Together, these data identify a 61 amino acid stretch of the T domain,
      corresponding to the region which includes alpha-helices TH8 and TH9 in the
      crystal structure of DT, as the channel-forming region of the toxin.

PMID- 7516433
TI  - Structure function relationships in diphtheria toxin channels: II. A residue
      responsible for the channel's dependence on trans pH.
AB  - Ion-conducting channels formed in lipid bilayers by diphtheria toxin are highly
      pH dependent. Among other properties, the channel's single channel conductance
      and selectivity depend on proton concentrations on either side of the membrane.
      We have previously shown that a 61 amino acid fragment of DT is sufficient to
      form a channel having the same pH-dependent single channel properties as that of
      the intact toxin. This region corresponds to an alpha-helical hairpin in the
      recently published crystal structure of DT in solution; the hairpin contains two
      alpha-helices, each long enough to span a membrane, connected by a loop of about
      nine residues. This paper reports on the single channel effects of mutations
      which alter the two negatively charged residues in this loop. Changing Glutamate
      349 to neutral glutamine or to positive lysine has no effect on the DT channel's
      single channel conductance or selectivity. In contrast, mutations of Aspartate
      352 to neutral asparagine (DT-D352N) or positive lysine (DT-D352K) cause
      progressive reductions in single channel conductance at pH 5.3 cis/7.2 trans (in
      1 M KCl), consistent with this group interacting electrostatically with ions in
      the channel. The cation selectivity of these mutant channels is also reduced from
      that of wild-type channels, a direction consistent with residue 352 influencing
      permeant ions via electrostatic forces. When both sides of the membrane are at pH
      4, the conductance difference between wild-type and DT-D352N channels is minimal,
      suggesting that Asp 352 (in the wild type) is neutral at this pH. Differences
      observed between wild-type and DT-D352N channels at pH 4.0 cis/7.2 trans (with a
      high concentration of permeant buffer in the cis compartment) imply that residue
      352 is on or near the trans side of the membrane. Comparing the conductances of
      wild-type and DT-D352K channels at large (cis) positive voltages supports this
      conclusion. The trans location of position 352 severely constrains the number of
      possible membrane topologies for this region.

PMID- 7516435
TI  - Correlations between changes in membrane capacitance induced by changes in ionic
      environment and the conductance of channels incorporated into bilayer lipid
      membranes.
AB  - The action of metal polycations and pH on ionic channels produced in bilayer
      lipid membranes (BLM) by three different toxins was studied by measuring membrane
      capacitance and channel conductance. Here, we show that critical concentrations
      of Cd2+, La3+ or Tb3+ induce complex changes in membrane capacitance. The time
      course of capacitance changes is similar to the time course of channel blocking
      by these ions at low concentration. No changes in BLM capacitance or conductance
      were observed in the range of pH 5.8-9.0. A pH shift from 7.4 to 3-4 or 11-12
      induced large changes in BLM capacitance and channel conductance. For all studied
      channel-forming proteins, the initial capacitance increase preceded the
      conductance decrease caused by addition of polycations or by a change in pH. A
      close relationship between membrane lipid packing and ion channel protein is
      suggested.

PMID- 7516438
TI  - Nucleolytic inactivation and degradation of the RNase III processed pnp message
      encoding polynucleotide phosphorylase of Escherichia coli.
AB  - The two cleavages made by RNase III in the transcripts of the pnp gene of
      Escherichia coli, 80 nucleotides upstream of the coding sequence of
      polynucleotide phosphorylase, were previously demonstrated to trigger the rapid
      degradation of the pnp messenger. In this paper, we demonstrate that the 5' end
      of the RNase III processed pnp mRNA is attacked by ribonucleases more efficiently
      than the rest of the molecule. Several 5' extremities resulting from cleavages
      occurring in the first 500 nucleotides of the pnp transcript have been
      identified. Three of them referred to as X, Y and W occur in the wild-type strain
      at the beginning of the coding sequence of the pnp mRNA. The mRNA appears to be
      cleaved more efficiently at the X site, proximal to the initiation codon, than at
      sites Y and W located downstream. In vitro, the maturation at X is catalysed by
      RNase E but not by RNase III. Accumulation of RNA processed at X in RNase E
      deficient strains leads us to postulate that X is a high affinity primary site
      which is slowly cleaved by the residual activity of thermosensitive RNase E at
      non-permissive temperature and that secondary sites located downstream are
      processed less efficiently than X. Taken together, our results suggest that in
      wild-type E. coli the degradation of the RNase III processed mRNA is mediated by
      RNase E.

PMID- 7516436
TI  - Adenosine discriminates between the caffeine and adenine nucleotide sites on the
      sheep cardiac sarcoplasmic reticulum calcium-release channel.
AB  - Calcium-release channels of sheep cardiac sarcoplasmic reticulum were
      incorporated into phosphatidylethanolamine bilayers and single channel currents
      were recorded under voltage-clamp conditions. The effect of adenosine on single
      channel conductance and gating was investigated, as were the interactions between
      adenosine and caffeine and adenosine and alpha, beta-methylene ATP. Addition of
      adenosine (0.5-5 mM) to the cytosolic but not the luminal side of the membrane
      increased the open probability of single calcium-activated calcium-release
      channels by increasing the frequency and duration of open events, yielding an
      EC50 of 0.75 mM at 10 microM activating Ca2+. Addition of 1 mM caffeine
      potentiated the effects of adenosine at 10 or 100 microM-activating cytosolic
      calcium, but had no effect on the inability of adenosine to activate the channel
      at 80 pM calcium, suggesting discrete sites of action on the calcium-release
      channel for adenosine and caffeine. In contrast, addition of 100 microM alpha,
      beta-methylene-ATP decreased single channel open probability in the presence of
      adenosine, suggesting that these compounds act on the same site on the channel.
      Activation of single channel opening by adenosine, or by adenosine together with
      caffeine, had no effect on single channel conductance or the Ca2+/Tris+
      permeability ratio. Channels activated by adenosine were characteristically
      modified by ryanodine and blocked by microM ruthenium red or mM magnesium. These
      results show that adenosine activates the sheep cardiac sarcoplasmic reticulum
      Ca(2+)-release channel by increasing the frequency and duration of open events in
      a Ca(2+)-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516437
TI  - Basolateral potassium membrane permeability of A6 cells and cell volume
      regulation.
AB  - The K+ permeabilities (86Rb(K) transport) of the basolateral membranes (JbK) of a
      renal cell line (A6) were compared under isosmotic and hypo-osmotic conditions
      (serosal side) to identify the various components involved in cell volume
      regulation. Changing the serosal solution to a hypo-osmotic one (165 mOsm)
      induced a fast transient increase in Cai (max < 1 min) and cell swelling (max at
      3-5 min) followed by a regulatory volume decrease (5-30 min) and rise in the SCC
      (stabilization at 30 min). In isosmotic conditions (247 mOsm), the 86Rb(K)
      transport and the SCC were partially blocked by Ba2+, quinidine, TEA and
      glibenclamide, the latter being the least effective. Changing the osmolarity from
      isosmotic to hypo-osmotic resulted in an immediate (within the first 3-6 min)
      stimulation of the 86Rb(K) transport followed by a progressive decline to a
      stable value higher than that found in isosmotic conditions. A serosal Ca(2+)
      free media or quinidine addition did not affect the initial osmotic stimulation
      of JbK but prevented its "secondary regulation", whereas TEA, glibenclamide and
      DIDS completely blocked the initial JbK increase. Under hypo-osmotic conditions,
      the initial JbK increase was enhanced by the presence of 1 mM of barium and
      delayed with higher concentrations (5 mM). In addition, cell volume regulation
      was fully blocked by quinidine, DIDS, NPPB and glibenclamide, while partly
      inhibited by TEA and calcium-free media. We propose that a TEA- and glibenclamide
      sensitive but quinidine-insensitive increase in K+ permeability is involved in
      the very first phase of volume regulation of A6 cells submitted to hypo-osmotic
      media. In achieving cell volume regulation, it would play a complementary role to
      the quinidine-sensitive K+ permeability mediated by the observed calcium rise.

PMID- 7516440
TI  - [Amylase producing tumor].

PMID- 7516441
TI  - [Alpha fetoprotein-producing primary lung cancer].

PMID- 7516439
TI  - Five viral peptide-HLA-A2 co-crystals. Simultaneous space group determination and
      X-ray data collection.
AB  - We prepared and crystallized five complexes of the human histocompatibility
      molecule HLA-A2 with peptides derived from human immunodeficiency virus type 1,
      human T lymphotropic virus type 1, influenza A virus and hepatitis B virus
      proteins. Each HLA-A2 complex was refolded in vitro from insoluble proteins
      produced in bacteria; to crystallize, two of the complexes required seeding with
      microcrystals of another complex. Maintained at -160 degrees C, single co
      crystals of each of the five peptide-HLA-A2 complexes yielded complete X-ray
      diffraction data sets to a resolution of approximately 2.5 A. After a sufficient
      number of diffraction peaks were acquired during data collection, the direct
      analysis of integrated intensities established the point group of the co-crystal,
      thus allowing an efficient data collection strategy to be designed. The
      subsequent examination of systematic absences revealed that the five peptide-HLA
      A2 co-crystals formed in space groups P1, P2(1), or P2(1)2(1)2(1). Molecular
      replacement structure solutions yielded unambiguous protein electron density
      maps, thus confirming the space group determinations. The system of obtaining HLA
      A2 co-crystal structures described here is applicable to other crystallographic
      problems where structures of several related molecules from uncharacterized
      single crystals are required.

PMID- 7516442
TI  - [Whipple's disease].

PMID- 7516434
TI  - Structure-function relationships in diphtheria toxin channels: III. Residues
      which affect the cis pH dependence of channel conductance.
AB  - The conductance of channels formed by diphtheria toxin (DT) in lipid bilayer
      membrane depends strongly on pH. We have previously shown that a 61 amino acid
      region of the protein, denoted TH8-9, is sufficient to form channels having the
      same pH-dependent conductance properties as those of whole toxin channels. One
      residue in this region, Aspartate 352, is responsible for all the dependence of
      single channel conductance on trans pH, whereas another, Glutamate 349, has no
      effect. Here, we report that of the seven remaining charged residues in the TH8-9
      region, mutations altering the charge on H322, H323, H372, and R377 have minimal
      effects on single channel conductance; mutations of Glutamates 326, 327, or 362,
      however, significantly affect single channel conductance as well as its
      dependence on cis pH. Moreover, Glutamate 362 is titratable from both the cis and
      trans sides of the membrane, suggesting that this residue lies within the
      channel; it is more accessible, however, to cis than to trans protons. These
      results are consistent with the membrane-spanning topology previously proposed
      for the TH8-9 region, and suggest a geometric model for the DT channel.

PMID- 7516443
TI  - [Drug-induced organic mood disorders].
AB  - Firstly, we reviewed the drugs (ex, corticosteroid, interferon) which were
      thought to be related to organic mood disorders in the literature, and discussed
      a number of problems with assessment of drug-induced mental disorders. Next, we
      investigated 1) the antidepressant-induced switch rate from depression to mania
      and 2) the latency from administration to manic onset in three groups (Major
      depression: single episode, Major depression: recurrent, Bipolar disorder:
      depressed). Our data showed, 1) the switch rate was 17.2, 14.3, 32.0% and 2) the
      latency to onset was 69.9, 65.9, 37.1 days, respectively. The latency to onset
      showed no significant difference in three groups. (ANOVA, p < 0.05) Clomipramine,
      amitriptyline, imipramine, and dosulepin had the higher switch rate above 10%.

PMID- 7516444
TI  - Roles of histological findings and serum AFP levels in the prognosis of AFP
      producing gastric cancers.
AB  - We investigated the roles of histological findings and serum AFP levels in the
      prognosis of gastric cancers which produce AFP. We considered the typical
      features of such gastric cancers to be the medullary growth of undifferentiated
      cancer cells with clear, or slightly eosinophilic, abundant cytoplasm and
      pleomorphic large round nuclei, forming either papillary clear carcinomas or
      hepatoid carcinomas. Seventeen patients with AFP-producing gastric cancers were
      observed in the period, 1979-1991. They were divided into two groups: those with
      (n 5) and those without (n 12) the typical histological features mentioned above.
      Their clinicopathological findings and prognoses were compared. Both groups
      showed a male dominance, gross Borrmann's type 2 or 3 appearances, diagnoses made
      at an advanced stage and metastatic involvements of the liver. The patients with
      the typical histological features showed a significantly higher AFP serum level
      and a significantly shorter survival. The patients who lacked the typical
      findings, and with serum AFP levels > or = 100 ng/ml, had poorer prognoses, while
      those lacking the typical histological features, and serum AFP levels < 100 ng/ml
      had better prognoses. The combination of histological findings and serum AFP
      level appeared to be useful in predicting the prognosis of AFP-producing gastric
      cancers. Intensive adjuvant therapy, e.g., chemotherapy administered via hepatic
      arterial infusion, may be indicated for patients at a high risk of recurrence
      following curative surgery.

PMID- 7516445
TI  - Clinical significance of prostate specific antigen for early stage prostate
      cancer detection.
AB  - The characteristics of serum prostate specific antigen (PSA) in normal Japanese
      men were studied in 1480 subjects examined by mass screening (MS) for prostate
      cancer (Pca) in Gunma Prefecture in 1992. The serum PSA concentration was
      correlated with patient age. The average serum PSA level increased by 0.04
      ng/ml/year. The upper normal limits (95 percentiles) of age specific PSA for
      normal men are 1.33 ng/ml for those aged 39-49 years, 3.65 ng/ml for those aged
      50-59 years, 4.06 ng/ml for those aged 60-69 years, 5.09 ng/ml for those aged 70
      79 years and 5.66 ng/ml for those aged 80-89 years. Among 227 normal men examined
      by our MS in 1991 and 1992, the PSA velocity (PSAV) was calculated to be 0.05
      ng/ml/year. Among 10 Pca patients with normal PSA levels (< 6 ng/ml) detected
      previously by our MS, three had an abnormal PSAV. We demonstrated the possibility
      that PSA density could distinguish between Pca and benign prostate hypertrophy.
      The significance of PSA as a Pca screening modality should be evaluated across
      multiple age ranges and in combination with previous PSA data and/or prostate
      volume estimated by sonography.

PMID- 7516446
TI  - Developmental changes of transmitter gated channels.

PMID- 7516447
TI  - A stretch-activated cation channel in the apical membrane of A6 cells.
AB  - A stretch-activated (SA) cation channel was investigated in the apical membrane
      of cultured kidney tubule cells (A6) with the patch-clamp technique. The mean
      numbers of open channels increased from 0.005 (without suction) to 0.05, 0.11,
      and 0.30 at pressures of -32, -48, and -64 cmH2O in the pipette, respectively
      (cell-attached patch). The channel activity increased at hyperpolarized membrane
      potentials and decreased with increasing Ca2+ in the pipette. It was completely
      blocked by 10 microM gadolinium in the pipette when suction was between -16 and 
      48 cmH2O. The channel was permeable to Na+, K+, and Ca2+, but not to Cl-. The
      single-channel conductances (120 mM NaCl in the pipette) were decreased by adding
      2-10 mM Ca2+ in the pipette solution: they were 57.8 +/- 1.6, 36.4 +/- 3.3, 28.2
      +/- 3.4, and 25.9 +/- 1.3 pS with 0.5, 2, 4, and 10 mM Ca2+, respectively. When
      the NaCl in the pipette was replaced with 80 mM CaCl2, the conductance was 25.6
      pS. These results indicate that when cells are stretched in a standard solution
      (Ca(2+)-containing Na(+)-rich solution), Na+ and Ca2+ enter the cell through the
      SA channel. The SA channel in A6 cells may be responsible for the Na+ and Ca2+
      entry pathway which is sensitive to membrane stretch.

PMID- 7516448
TI  - [Neurogenic inflammation in nasal hyperreactivity].
AB  - The role of neuropeptides in nasal hyperreactivity was examined in guinea pigs by
      histochemical and pharmacological study. Intranasal application of toluene
      diisocynate (TDI) induced nasal hyperreactivity symptoms: sneezing and watery
      rhinorrhea, and decreased histamine content in the nasal mucosa in guinea pigs
      sensitized with TDI. The immunoreactivity of substance P (SP) and calcitonin gene
      related peptide (CGRP) in the nerve terminals in the nasal mucosa was increased
      after intranasal application of TDI. We also observed a decrease in the
      immunoreactivity of SP and CGRP, and an increase in their mRNA expression in
      trigeminal ganglion neurons. These findings indicate that exposure to TDI
      enhanced the biosynthesis of both SP and CGRP in the trigeminal ganglion neurons
      and their axonal transportation to the terminals in the nasal mucosa. In animals
      pretreated with capsaicin before sensitization, TDI did not induce nasal allergy
      like behavior and histamine release in the nasal mucosa. Since capsaicin depletes
      SP and CGRP in the sensory nerves, this finding indicates neuropeptide-mediated
      histamine release in the nasal mucosa. All these findings suggest that, on
      exposure to TDI, the antidromic release of SP and CGRP in the nasal mucosa
      triggers the release of histamine, resulting in the development of symptom of
      nasal hyperreactivity.

PMID- 7516449
TI  - [Expression of adhesion molecules in bronchial asthma].
AB  - Eosinophilic infiltration into the airway is thought to be a key process to
      induce late asthmatic response, and it seems to be very important for the
      treatment of bronchial asthma to study the precise mechanisms of selective
      infiltration of eosinophils. In this study, we examined which adhesion molecules
      were involved in selective eosinophil infiltration into the airway, by
      immunohistochemistry, immuno-electron microscopy and in situ hybridization
      methods. In the sputum and peripheral blood eosinophils of asthmatics, Mac-1 was
      strongly expressed and LFA-1, VLA-4 and sLe-X were also expressed. In the
      bronchial submucosa of lung tissues from autopsy and biopsy of patients with
      bronchial asthma, immunoreactivity of ICAM-1 was detected in the endothelial
      cells, the basal layer of the bronchial epithelium, mononuclear cells and
      extracellular spaces, and VCAM-1 was also detected in the endothelial cells, but
      ELAM-1 was weakly detected. In addition, immunoreactivities of Mac-1, LFA-1, and
      VLA-4 were detected in eosinophils infiltrated into the bronchial submucosa, but
      sLe-X was weakly detected. These results suggest that binding between ICAM-1 and
      Mac-1 or LFA-1, VCAM-1 and VLA-4, not but ELAM-1 and sLe-X, is mainly involved in
      eosinophil infiltration into the airway in allergic reaction such as bronchial
      asthma.

PMID- 7516451
TI  - [Pathogenesis of idiopathic pulmonary fibrosis--is hepatitis C virus involved?].
AB  - Hepatitis C virus (HCV) is a new virus discovered in 1989. Since HCV is known to
      cause fibrotic changes in the liver, we studied whether HCV is involved in the
      pathogenesis of idiopathic pulmonary fibrosis (IPF). Firstly, we assessed anti
      HCV antibodies by enzyme-linked immunosorbent assay (ELISA) in the sera obtained
      from 66 IPF patients (46 males and 20 females; mean age +/- SEM, 61.5 +/- 10.1).
      We observed a significantly high prevalence of anti-HCV antibodies in IPF
      compared with 9,464 age-matched controls (28.8% vs 3.66%, p < 0.05). To confirm
      the results, recombinant immunoblotting assay (RIBA) was conducted on the 19
      ELISA-positive sera, and 8 sera (12.2%) were found to be definitely positive.
      Secondly, we searched for HCV in the blood of IPF patients by reverse
      transcription-polymerase chain reaction. As preliminary data, four out of 28
      cases (14.3%), all of which were pathologically diagnosed as UIP, were positive
      for HCV. In conclusion, although further investigation is required, a high
      prevalence of anti-HCV antibodies and the existence of HCV itself in the blood
      may suggest the possibility that HCV infection plays an important role in the
      pathogenesis of IPF.

PMID- 7516450
TI  - [Chemotherapy for small cell lung cancer].
AB  - This paper describes the results of a randomized trial comparing alternating
      chemotherapy with standard chemotherapy and of a trial of dose intensive
      chemotherapy with or without recombinant human granulocyte-colony stimulating
      factor (G-CSF) in small cell lung cancer (SCLC). 1) Between April 1985 and May
      1988, the Japan Clinical Oncology Group conducted a randomized phase III trial of
      cyclophosphamide, doxorubicin and vincristine (CAV) versus cisplatin and
      etoposide (PE) versus CAV alternating with PE (CAV/PE). Three hundred patients
      were entered in the study, and 288 of them were eligible for analysis. The
      response rates for PE (78%) and CAV/PE (76%) were significantly higher than the
      rate for CAV (55%) (p < 0.01). The median survival time (MST) with CAV/PE (11.8
      months) was superior to that with CAV (9.9 months) (p = 0.027) or that with PE
      (9.9 months) (p = 0.056); however, the survival advantage of CAV/PE disappeared
      when the data were adjusted for prognostic factors. These results have shown that
      CAB/PE is a reasonable approach for the management of SCLC. 2) Between May 1989
      and September 1991, we carried out a randomized study to determine whether the
      dose intensity of the weekly CODE (cyclophosphamide, Oncovin, doxorubicin and
      etoposide) chemotherapy could be increased by the addition of G-CSF support.
      Sixty-three patients were entered in this study. The use of G-CSF was associated
      with a reduced incidence of neutropenic fever and an increase in the dose
      intensity. The MST for the patients treated with CODE plus G-CSF (58 weeks) was
      significantly longer than that for the patients treated with CODE alone (36
      weeks). The results of this study showed that dose intensive weekly chemotherapy
      may improve the outcome of patients with ED-SCLC.

PMID- 7516452
TI  - Induction of nitric oxide synthase in rat immune complex glomerulonephritis.
AB  - Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine
      by a family of nitric oxide synthases (NOS). Previously we have shown that NO is
      synthesized ex vivo by glomeruli obtained from animals with acute immune complex
      glomerulonephritis. We have now sought evidence for the in vivo induction of NOS
      in glomeruli by immunohistochemistry using specific antisera raised against a
      peptide sequence of inducible mouse macrophage NOS and by in situ hybridization.
      The expression of the enzyme was studied in kidneys of rats with acute unilateral
      immune complex glomerulonephritis, induced by cationized IgG, by
      immunohistochemistry. Inducible NOS (iNOS) was present in glomeruli in nephritic
      (left) kidneys at the time of maximum macrophage infiltration, both within
      intraglomerular mononuclear cells and cells emigrating into Bowman's space. iNOS
      expressing cells were also present in interstitial infiltrates. There was no
      expression in normal rat kidneys or in glomeruli in the non-nephritic (right)
      kidneys of experimental rats. In situ hybridization confirmed the
      immunohistochemical localization. These results provide the first direct evidence
      for the presence and localization of inducible NOS in glomeruli and support a
      significant role for NO in the pathogenesis of immune complex glomerulonephritis.

PMID- 7516453
TI  - Location of an inducible nitric oxide synthase mRNA in the normal kidney.
AB  - An inducible nitric oxide synthase (iNOS) mRNA was found primarily in the outer
      medulla of normal rat kidney. Identification of the mRNA was based upon the
      specificity of the oligonucleotide primers used for PCR amplification, PCR
      Southern blot analysis and the nucleic acid sequence of the cloned PCR product.
      In addition to the outer medulla, glomeruli prepared from normal rat kidney
      contained significant amounts of an iNOS mRNA. These results suggest that there
      may be tonic influences in the outer medulla of the normal rat kidney resulting
      in the "steady-state" presence of an iNOS mRNA. Cortical tubules and the inner
      medulla were found to contain detectable but lesser amounts of the iNOS mRNA. The
      outer medulla was microdissected into proximal straight tubule (PST), medullary
      thick ascending limb (MTAL), medullary collecting duct (MCD) and vasa recta
      bundle (VRB). The iNOS mRNA was found primarily in the MTAL with minor amounts in
      the MCD and VRB of normal rat kidney. Animals were injected with
      lipopolysaccharide (LPS) and sacrificed 24 hours later. Treatment with LPS caused
      at least a 20-fold increase in the amount of iNOS mRNA in the liver or in
      macrophages isolated from the peritoneum. Endotoxin treatment led to over a 10
      fold increase in iNOS mRNA content in glomeruli and the inner medulla. The iNOS
      mRNA level of the outer medulla was increased two- to threefold due to LPS
      treatment.

PMID- 7516454
TI  - Incidence of antibodies to hepatitis C virus in patients undergoing chronic
      dialysis and CAPD.
AB  - We measured antibodies to hepatitis C virus (anti-HCV) in patients who were
      receiving hemodialysis or continuous ambulatory peritoneal dialysis (CAPD). Sixty
      seven patients (28%) were anti-HCV positive. The anti-HCV positive frequency
      increased with the time of treatment with dialysis, the frequency being 50% with
      a dialysis period > or = 10 years. The frequency of anti-HCV positivity was
      similar in patients with a history of blood transfusion (48/152, 32%) and in
      those without this history (19/89, 21%, p > 0.05). Therefore, in addition to
      blood transfusion, there may be other routes of HCV infection associated with
      long-term dialysis. Chronic liver disease was observed in 31% (21/67) of the
      patients positive for anti-HCV but in only 6% (11/174) of the negative patients
      (p < 0.01). HCV seems to be important as a cause of chronic liver disease in
      dialysis patients.

PMID- 7516455
TI  - Comparison of proteolytic variables in a lean and obese strain of pig at the ages
      of 2.5 and 7 months.
AB  - The mode(s) of skeletal muscle protein turnover as well as muscle and animal
      growth may be studied by using lean and obese animals as models. The objectives
      of this study were to look at proteolytic variables implicated in these
      processes. A lean and obese strain of swine from similar genetic lineage (Duroc x
      Yorkshire, 50:50) have been well established and may prove ideal for this
      purpose. This study was done in two phases. Phase I included eight lean and eight
      obese pigs at 2.5 months of age, and phase II was identical, but the pigs were 7
      months old. Longissimus muscle samples were processed immediately after
      euthanasia for activity measurements of mu-calpain, m-calpain, calpastatin, and
      lysosomal cathepsins B and B + L. Additional samples were taken for DNA, RNA, and
      total protein determinations. In phase I, total calpastatin activity, total and
      specific cathepsin B+L activity, and total protein/g muscle were greater in the
      obese pigs than in the lean pigs. In contrast, DNA and RNA/g muscle were greater
      in the lean pigs. No other differences were observed in phase I. In phase II,
      total calpastatin activity and total cathepsin B activity were greater in the
      obese pigs than in the lean pigs. No other differences were observed in phase II.
      From phase I to phase II, mu-calpain total activity increased in the lean pigs
      but not in the obese pigs and calpastatin activity decreased in both lean and
      obese pigs; however, the phase-II-obese and phase-I-lean total calpastatin
      concentrations were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516456
TI  - Silver stained nucleolar organizer region proteins and Helix pomatia agglutinin
      immunostaining in esophageal carcinoma: correlated prognostic factors.
AB  - The number of nucleolar organizer region proteins identified by silver staining
      (AgNORs) and alterations in cell surface glycoproteins identified by Helix
      pomatia agglutinin (HPA) immunostaining were studied in 96 primary esophageal
      carcinomas. The number of AgNORs increased with increasing depth of cancer
      invasion, venous involvement, lymphatic invasion, and tumor stage. Positivity of
      HPA staining correlated significantly with increasing depth of cancer invasion,
      venous invasion, and tumor stage. Forty of 42 HPA negative cases had low AgNORs
      numbers (< 4), while 39 of 54 HPA positive cases had high AgNORs numbers (> or =
      4) (P = 0.0001). The survival rate of patients with stage III and IV disease was
      significantly poorer for those with a high AgNORs score and HPA positivity than
      in those with a low AgNORs score and HPA negativity. The present study indicates
      that the AgNORs score is positively correlated with positive HPA staining and
      that tumors having both factors represent a subgroup of esophageal carcinomas
      with poor prognosis.

PMID- 7516457
TI  - Prostate cancer screening.

PMID- 7516458
TI  - Deranged activity of the CD44 gene and other loci as biomarkers for progression
      to metastatic malignancy.
AB  - About one in three people in modern industrialised countries die of the
      consequences of malignant tumours or are found to carry an unsuspected one at the
      time of autopsy. Early resection of such lesions and appropriate adjuvant therapy
      is very effective in curing the disease. There is therefore a strong clinical
      incentive to find effective methods of early diagnosis, assessment of prognosis
      and treatment of neoplastic lesions and research on this topic is directed at a
      numerically significant medical problem. Recently it has been found that many
      human tumours show severe abnormalities in the expression of the CD44 gene which
      increase with progression to metastatic malignancy. By alternative splicing
      mechanisms this gene codes for a family of heavily glycosylated cell surface
      proteins involved in many important cellular activities. In neoplasia there is
      gross overexpression of various products of the gene associated with disorderly
      splicing, which can be detected in clinical samples with the sensitive technique
      of reverse transcription-polymerase chain reaction (RT-PCR). These disturbances
      begin early in the neoplastic process and can be detected in very small biopsy
      samples. It has also been shown that it is possible to achieve non-invasive
      diagnosis of malignancy by analysis of CD44 expression in exfoliated cells in
      body fluids and waste products. The potential significance of these observations
      for early diagnosis of symptomatic cancer and for screening of the population for
      asymptomatic lesions are readily seen and await further investigation. Separate
      work in our laboratory has succeeded in DNA-mediated transfer of metastatic
      capability through two rounds of transfection into non-metastatic tumour cells
      and a metastasis-associated human DNA fragment has been recovered from the
      transfectants and sequenced. Using primers designed to anneal to a coding region
      identified by computer analysis within the novel sequence, it has been shown with
      RT-PCR that it is heavily expressed in metastatic cancer tissues, but not in
      corresponding normal ones. This could be of value in assessing the prognosis of
      patients using small biopsy samples from their primary tumours and the potential
      of this sequence for such purposes and for possible therapeutic intervention is
      currently being explored. Recent work in several laboratories has shown that
      elevated expression of certain other specific growth factor genes, including c
      met and EGFR, correlates with metastatic capability. Combined evaluation of such
      markers in further studies will in time give useful information on the prognosis
      of individual patients to guide therapeutic decisions and the implications of
      these recent advances for clinical practice and future research are discussed
      below.

PMID- 7516459
TI  - Genetic testing and counselling for congenital bilateral absence of the vas
      deferens.

PMID- 7516462
TI  - [Certain inhibitors of proteolysis in blood serum of workers engaged in
      production of iron-manganese alloys].
AB  - In metallurgic workers exposed to manganese, ferric oxides, chromates, noise,
      thermal radiation and enhanced temperature in surroundings, a lower level of
      alpha 2-macroglobulin at an unlowered level of alpha 1-antitrypsin was observed.
      There was no relationship between either the length of employment or chronic
      bronchitis and level of alpha 1-antitrypsin and alpha 2-macroglobulin in the
      blood of workers under study.

PMID- 7516461
TI  - Diagnosis of growth hormone deficiency in adults.

PMID- 7516460
TI  - Prevalence of hepatitis C antibodies in clinical health-care workers.
AB  - Health-care workers are known to be at risk from occupational transmission of
      blood-borne viruses, including hepatitis C. There may be serious implications
      following infection with hepatitis C including possible transmission to patients.
      We determined the prevalence of hepatitis C virus (HCV) antibodies among health
      care workers at risk of occupational contact with blood and body fluids and among
      source patients in reported blood-exposure incidents. Anonymised stored blood
      samples from health-care workers immunised against hepatitis B virus since 1991
      (n = 1053) and blood samples from source patients in needlestick injuries
      (retrospective and prospective) since 1989 (n = 373) were analysed. 3 (0.28%) of
      the serum samples from health-care workers were found to be anti-HCV-positive. 17
      (8.5%) of 200 source patients tested retrospectively between January 1989 and
      January 1992, and 24 (13.9%) of 173 source patients tested prospectively between
      January 1992 and June 1993 were anti-HCV-positive. During the second period, 15
      (10.6%) of 142 source patients tested for human immunodeficiency virus (HIV) were
      positive and 7 (3.8%) of 184 source patients tested for hepatitis B surface
      antigen were positive. 6 of 24 (25%) HCV-infected patients were diagnosed only
      after the incident; for hepatitis B, 2 (33%) of patients were diagnosed after the
      incident, and for HIV all patients were previously diagnosed. The seroprevalence
      of HCV among these health-care workers is no higher than that reported in blood
      donors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516463
TI  - Properties of the ryanodine receptor present in the sarcoplasmic reticulum from
      lobster skeletal muscle.
AB  - Microsomal sarcoplasmic reticulum (SR) fractions from lobster skeletal muscle
      were found to bind [3H]-ryanodine. [3H]-ryanodine binding was enhanced by AMP,
      Ca2+ and caffeine, and significantly diminished by ATP, Ba2+ and Sr2+.
      Furthermore, dantrolene and ruthenium red, two classical inhibitors of Ca2+
      release from the SR, blocked [3H]-ryanodine binding. Similarly, tetracaine, known
      to block the charge movement associated with excitation-contraction coupling in
      vertebrate muscle, inhibited the binding of the alkaloid. Our lobster SR
      preparation exhibited a single high-affinity ryanodine binding site (Kd = 6.6 nM,
      Bmax = 10 pmol/mg protein). Since SDS-PAGE of the SR proteins revealed a major
      band c. 565 kDa which comigrated with the putative ryanodine receptor from both
      rat and chicken skeletal muscle, we concluded that lobster skeletal muscle is
      equipped with the 565 kDa ryanodine receptor. Finally, incorporation of the SR
      microsomal fraction from lobster into planar bilayer membranes revealed the
      presence of a ryanodine-sensitive Ca2+ channel activity (160 pS in symmetrical
      200 mM CsCl solutions). We concluded that both the crustacean and vertebrate
      skeletal muscle ryanodine receptor share the relevant properties such as
      molecular weight and affinity for ryanodine and inositol 1,4,5 triphosphate.
      However, there are important differences between the two receptors including
      differential effects of the alkaloid on the Ca2+ release channel and modulation
      of the receptor by nucleotides.

PMID- 7516464
TI  - Acute hemodilution--a review.

PMID- 7516465
TI  - Proliferating cell nuclear antigen (pol30) mutations suppress cdc44 mutations and
      identify potential regions of interaction between the two encoded proteins.
AB  - In addition to its role as a processivity factor in DNA replication,
      proliferating cell nuclear antigen (PCNA) may function in the regulation of cell
      cycle progression. We present genetic evidence that PCNA interacts with the gene
      product of CDC44, an essential nucleotide-binding protein that encodes the large
      subunit of yeast replication factor C (K. Fien and B. Stillman, personal
      communication). Mutations in POL30 (PCNA) suppress cold-sensitive alleles of
      cdc44 that contain mutations in or near nucleotide-binding consensus domains, but
      they do not suppress a null allele. Thus, it appears that PCNA interacts with
      Cdc44p but cannot substitute for its function. pol30 mutations suppress
      additional phenotypes of cdc44 mutations, including the cold sensitivity that
      they were selected to suppress. This observation suggests an intimate association
      between PCNA and Cdc44p. Each of five independent pol30 mutants contains a unique
      single mutation that maps to a localized region on one face of the predicted
      three-dimensional structure of PCNA. This face identifies a region likely to be
      important for functional interaction between the CDC44 and POL30 gene products.

PMID- 7516466
TI  - Expression of a peptide inhibitor of protein phosphatase 1 increases
      phosphorylation and activity of CREB in NIH 3T3 fibroblasts.
AB  - We have examined the activity and phosphorylation state of the cyclic AMP (cAMP)
      response element binding factor (CREB) in intact NIH 3T3 cells following
      microinjection of expression plasmids encoding regulatory proteins of type 1
      (PP1) and 2A (PP2A) serine/threonine-specific protein phosphatases. Changes in
      CREB phosphorylation in the injected cells were monitored by indirect
      immunofluorescence using an affinity-purified antiserum (Ab5322) which
      specifically recognizes CREB phosphorylated at Ser-133, and changes in
      transcriptional activity of CREB were monitored by expression of a reporter gene
      regulated by cAMP. cAMP-stimulated phosphorylation in NIH 3T3 cells is normally
      transient, and as expected, after stimulation of cells with cell-permeable cAMP
      analogs, the level of phosphorylated CREB was found to initially increase and
      then return to a basal level within 4 h. Microinjection of an expression vector
      encoding a constitutively active form of inhibitor 1 (I-1), a PP1-specific
      inhibitor, by itself resulted in an apparent increase in phosphorylated CREB in
      unstimulated cells. Moreover, injection of the I-1 vector resulted in the
      prolonged appearance of phosphorylated CREB in cells after cAMP stimulation. In
      contrast, injection of a plasmid encoding simian virus 40 small t antigen, which
      interacts with PP2A to inhibit its activity towards several phosphoprotein
      substrates, had no effect on the phosphorylation state of CREB in stimulated or
      unstimulated NIH 3T3 cells. Consistent with these results, injection of the I-1
      expression vector activated expression from a coinjected CRE-lacZ reporter
      plasmid, indicating that the increased phosphorylation of CREB also activated its
      transcriptional activity. These results provide further evidence for a role of a
      PP1 as the primary protein (Ser/Thr) phosphatase regulating the dephosphorylation
      of Ser-133 and thereby limiting the transcriptional activity of CREB.

PMID- 7516468
TI  - An in vivo assay for the reverse transcriptase of human retrotransposon L1 in
      Saccharomyces cerevisiae.
AB  - L1 elements constitute a highly repetitive human DNA family (50,000 to 100,000
      copies) lacking long terminal repeats and ending in a poly(A) tail. Some L1
      elements are capable of retrotransposition in the human genome (Kazazian, H. H.,
      Jr., C. Wong, H. Youssoufian, A. F. Scott, D. G. Phillips, and S.E. Antonarakis,
      Nature (London) 332:164-166, 1988). Although most are 5' truncated, a consensus
      sequence of complete L1 elements is 6 kb long and contains two open reading
      frames (ORFs) (Scott, A. F., B. J. Schmeckpeper, M. Abdelrazik, C. T. Comey, B.
      O'Hara, J. P. Rossiter, T. Cooley, P. Health, K. D. Smith, and L. Margolet,
      Genomics 1:113-125, 1987). The protein encoded by ORF2 has reverse transcriptase
      (RT) activity in vitro (Mathias, S. L., A. F. Scott, H. H. Kazazian, Jr., J. D.
      Boeke, and A. Gabriel, Science 254:1808-1810, 1991). Because L1 elements are so
      numerous, efficient methods for identifying active copies are required. We have
      developed a simple in vivo assay for the activity of L1 RT based on the system
      developed by Derr et al. (Derr, L. K., J. N. Strathern, and D. J. Garfinkel, Cell
      67:355-364, 1991) for yeast HIS3 pseudogene formation. L1 ORF2 displays an in
      vivo RT activity similar to that of yeast Ty1 RT in this system and generates
      pseudogenes with unusual structures. Like the HIS3 pseudogenes whose formation
      depends on Ty1 RT, the HIS3 pseudogenes generated by L1 RT are joined to Ty1
      sequences and often are part of complex arrays of Ty1 elements, multiple HIS3
      pseudogenes, and hybrid Ty1/L1 elements. These pseudogenes differ from those
      previously described in that there are base pairs of unknown origin inserted at
      several of the junctions. In two of three HIS3 pseudogenes studied, the L1 RT
      appears to have jumped from the 5' end of a Ty1/L1 transcript to the poly(A)
      tract of the HIS3 RNA.

PMID- 7516467
TI  - GRB2 and phospholipase C-gamma 1 associate with a 36- to 38-kilodalton
      phosphotyrosine protein after T-cell receptor stimulation.
AB  - GRB2, a 25-kDa protein comprising a single SH2 domain flanked by two SH3 domains,
      has been implicated in linking receptor protein tyrosine kinases (PTKs) to the
      Ras pathway by interacting with the guanine nucleotide exchange protein SOS.
      Previous studies have demonstrated that GRB2 directly interacts with Shc, a proto
      oncogene product that is tyrosine phosphorylated upon receptor and nonreceptor
      PTK activation. In this report, we detected low levels of tyrosine
      phosphorylation of Shc and induced association with GRB2 upon T-cell receptor
      (TCR) stimulation. Instead, a prominent 36- to 38-kDa tyrosine phosphoprotein
      (pp36-38) associated with the SH2 domain of GRB2 and formed a stable complex with
      GRB2/SOS upon TCR stimulation. Cellular fractionation studies showed that whereas
      both GRB2 and SOS partitioned to the soluble and particulate fractions, pp36-38
      was present exclusively in the particulate fraction. This phosphoprotein had the
      same apparent mobility in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis as the phosphoprotein that associates with phospholipase C-gamma
      1 (PLC-gamma 1). Furthermore, following partial immunodepletion of GRB2 and of
      the associated pp36-38, there was a significant reduction in the amount of the 36
      kDa phosphoprotein associated with PLC-gamma 1, suggesting that a trimeric PLC
      gamma 1/pp36-38/GRB2 complex could form. In support of this notion, we have also
      been able to detect low levels of PLC-gamma 1 in GRB2 immunoprecipitates. We
      suggest that pp36-38 may be a bridging protein, coupling different signalling
      molecules to cytoplasmic PTKs regulated by the TCR.

PMID- 7516469
TI  - Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a
      function of SH3 domains.
AB  - Src homology 3 (SH3) domains mediate protein-protein interactions necessary for
      the coupling of cellular proteins involved in intracellular signal transduction.
      We previously established solution-binding conditions that allow affinity
      isolation of Src SH3-binding proteins from cellular extracts (Z. Weng, J. A.
      Taylor, C. E. Turner, J. S. Brugge, and C. Seidel-Dugan, J. Biol. Chem. 268:14956
      14963, 1993). In this report, we identified three of these proteins: Shc, a
      signaling protein that couples membrane tyrosine kinases with Ras; p62, a protein
      which can bind to p21rasGAP; and heterogeneous nuclear ribonucleoprotein K, a pre
      mRNA-binding protein. All of these proteins contain proline-rich peptide motifs
      that could serve as SH3 domain ligands, and the binding of these proteins to the
      Src SH3 domain was inhibited with a proline-rich Src SH3 peptide ligand. These
      three proteins, as well as most of the other Src SH3 ligands, also bound to the
      SH3 domains of the closely related protein tyrosine kinases Fyn and Lyn. However,
      Src- and Lyn-specific SH3-binding proteins were also detected, suggesting subtle
      differences in the binding specificity of the SH3 domains from these related
      proteins. Several Src SH3-binding proteins were phosphorylated in Src-transformed
      cells. The phosphorylation of these proteins was not detected in cells
      transformed by a mutant variant of Src lacking the SH3 domain, while there was
      little change in tyrosine phosphorylation of other Src-induced phosphoproteins.
      In addition, the coprecipitation of v-Src with two tyrosyl-phosphorylated
      proteins with M(r)s of 62,000 and 130,000 was inhibited by incubation with a Src
      SH3 peptide ligand, suggesting that the binding of these substrate proteins is
      dependent on interactions with the SH3 domain. These results strongly suggest a
      role for the Src SH3 domain in the recruitment of substrates to this protein
      tyrosine kinase, either through direct interaction with the SH3 domain or
      indirectly through interactions with proteins that bind to the SH3 domain.

PMID- 7516470
TI  - The U1 small nuclear ribonucleoprotein (snRNP) 70K protein is transported
      independently of U1 snRNP particles via a nuclear localization signal in the RNA
      binding domain.
AB  - Expression of the recombinant human U1-70K protein in COS cells resulted in its
      rapid transport to the nucleus, even when binding to U1 RNA was debilitated.
      Deletion analysis of the U1-70K protein revealed the existence of two segments of
      the protein which were independently capable of nuclear localization. One nuclear
      localization signal (NLS) was mapped within the U1 RNA-binding domain and
      consists of two typically separated but interdependent elements. The major
      element of this NLS resides in structural loop 5 between the beta 4 strand and
      the alpha 2 helix of the folded RNA recognition motif. The C-terminal half of the
      U1-70K protein which was capable of nuclear entry contains two arginine-rich
      regions, which suggests the existence of a second NLS. Site-directed mutagenesis
      of the RNA recognition motif NLS demonstrated that the U1-70K protein can be
      transported independently of U1 RNA and that its association with the U1 small
      nuclear ribonucleoprotein particle can occur in the nucleus.

PMID- 7516471
TI  - A DNA end-binding factor involved in double-strand break repair and V(D)J
      recombination.
AB  - We have identified a nuclear factor that binds to double-stranded DNA ends,
      independently of the structure of the ends. It had equivalent affinities for DNA
      ends created by sonication or by restriction enzymes leaving 5', 3', or blunt
      ends but had no detectable affinity for single-stranded DNA ends. Since X rays
      induce DNA double-strand breaks, extracts from several complementation groups of
      X-ray-sensitive mammalian cells were tested for this DNA end-binding (DEB)
      activity. DEB activity was deficient in three independently derived cell lines
      from complementation group 5. Furthermore, when the cell lines reverted to X-ray
      resistance, expression of the DEB factor was restored to normal levels. Previous
      studies had shown that group 5 cells are defective for both double-strand break
      repair and V(D)J recombination. The residual V(D)J recombination activity in
      these cells produces abnormally large deletions at the sites of DNA joining (F.
      Pergola, M. Z. Zdzienicka, and M. R. Lieber, Mol. Cell. Biol. 13:3464-3471, 1993,
      and G. Taccioli, G. Rathbun, E. Oltz, T. Stamato, P. Jeggo, and F. Alt, Science
      260:207-210, 1993), consistent with deficiency of a factor that protects DNA ends
      from degradation. Therefore, DEB factor may be involved in a biochemical pathway
      common to both double-strand break repair and V(D)J recombination.

PMID- 7516473
TI  - Disease-activated transcription factor: allergic reactions in human skin cause
      nuclear translocation of STAT-91 and induce synthesis of keratin K17.
AB  - Epidermal keratinocytes have important immunologic functions, which is apparent
      during wound healing, in psoriasis, and in allergic and inflammatory reactions.
      In these processes, keratinocytes not only produce cytokines and growth factors
      that attract and affect lymphocytes but also respond to the polypeptide factors
      produced by the lymphocytes. Gamma interferon (IFN-gamma) is one such signaling
      polypeptide. Its primary molecular effect is activation of specific transcription
      factors that regulate gene expression in target cells. In this work, we present a
      molecular mechanism of lymphocyte-keratinocyte signaling in the epidermis. We
      have induced cutaneous delayed-type hypersensitivity reactions that are
      associated with an accumulation of lymphocytes. These resulted in activation and
      nuclear translocation of STAT-91, the IFN-gamma-activated transcription factor,
      in keratinocytes in vivo and subsequent induction of transcription of keratin
      K17. Within the promoter of the K17 keratin gene, we have identified and
      characterized a site that confers the responsiveness to IFN-gamma and that binds
      the transcription factor STAT-91. Other keratin gene promoters tested were not
      induced by IFN-gamma. These results characterize at the molecular level a
      signaling pathway produced by the infiltration of lymphocytes in skin and
      resulting in the specific alteration of gene expression in keratinocytes.

PMID- 7516472
TI  - Direct stimulation of Vav guanine nucleotide exchange activity for Ras by phorbol
      esters and diglycerides.
AB  - We recently identified Vav as a Ras-activating guanine nucleotide exchange factor
      (GEF) stimulated by a T-cell antigen receptor-coupled protein tyrosine kinase
      (PTK). Here, we describe a novel, protein kinase-independent alternative pathway
      of Vav activation. Phorbol ester, 1,2-diacylglycerol, or ceramide treatment of
      intact T cells, Vav immunoprecipitates, or partially purified Vav generated by in
      vitro translation or COS-1 cell transfection stimulated the Ras exchange activity
      of Vav in the absence of detectable tyrosine phosphorylation. GEF activity of gel
      purified Vav was similarly stimulated by phorbol myristate acetate (PMA).
      Stimulation was resistant to PTK and protein kinase C inhibitors but was blocked
      by calphostin, a PMA and diacylglycerol antagonist. In vitro-translated Vav
      lacking its cysteine-rich domain, or mutated at a single cysteine residue within
      this domain (C528A), was not stimulated by PMA but was fully activated by p56lck.
      This correlated with increased binding of radiolabeled phorbol ester to COS-1
      cells expressing wild-type, but not C528A-mutated, Vav. Thus, Vav itself is a PMA
      binding and -activated Ras GEF. Recombinant interleukin-1 alpha stimulated Vav
      via this pathway, suggesting that diglyceride-mediated Vav activation may couple
      PTK-independent receptors which stimulate production of lipid second messengers
      to Ras in hematopoietic cells.

PMID- 7516474
TI  - Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of
      human T lymphocytes.
AB  - Peripheral blood T lymphocytes require two sequential mitogenic signals to
      reenter the cell cycle from their natural, quiescent state. One signal is
      provided by stimulation of the T-cell antigen receptor, and this induces the
      synthesis of both cyclins and cyclin-dependent kinases (CDKs) that are necessary
      for progression through G1. Antigen receptor stimulation alone, however, is
      insufficient to promote activation of G1 cyclin-Cdk2 complexes. This is because
      quiescent lymphocytes contain an inhibitor of Cdk2 that binds directly to this
      kinase and prevents its activation by cyclins. The second mitogenic signal, which
      can be provided by the cytokine interleukin 2, leads to inactivation of this
      inhibitor, thereby allowing Cdk2 activation and progression into S phase.
      Enrichment of the Cdk2 inhibitor from G1 lymphocytes by cyclin-CDK affinity
      chromatography indicates that it may be p27Kip1. These observations show how
      sequentially acting mitogenic signals can combine to promote activation of cell
      cycle proteins and thereby cause cell proliferation to start. CDK inhibitors have
      been shown previously to be induced by signals that negatively regulate cell
      proliferation. Our new observations show that similar proteins are down-regulated
      by positively acting signals, such as interleukin 2. This finding suggests that
      both positive and negative growth signals converge on common targets which are
      regulators of G1 cyclin-CDK complexes. Inactivation of G1 cyclin-CDK inhibitors
      by mitogenic growth factors may be one biochemical pathway underlying cell cycle
      commitment at the restriction point in G1.

PMID- 7516477
TI  - Checks for chromosomal instability in Gorlin and non-Gorlin basal-cell carcinoma
      patients.
AB  - The naevoid basal-cell carcinoma syndrome (NBCCS) is an autosomal dominant
      disorder with multiple basal-cell carcinomas, an increased risk for other
      neoplasms, and various malformations. Chromosome instability has been implicated
      in the pathogenesis of this syndrome, but these reports are somewhat
      contradictory. We have investigated five patients, two with confirmed NBCCS and
      three suspected. No evidence for chromosome instability was found in lymphocytes
      at three sample times after stimulation using metaphase aberration analysis,
      sister-chromatid exchange (SCE) in second division cells, or micronuclei. A
      significant lengthening of the cell cycle was found for the two confirmed NBCCS
      patients, but not for the suspected cases.

PMID- 7516479
TI  - Protein patterns in tissues of fetuses with radiation-induced gastroschisis.
AB  - We have used two-dimensional gel electrophoresis coupled with computer-assisted
      data analysis to monitor protein expression in the liver of mouse fetuses with
      and without gastroschisis after X-irradiation of embryos during the 1-cell stage.
      A significantly higher frequency of changes in protein expression was observed in
      liver from irradiated fetuses with gastroschisis than from irradiated fetuses
      without gastroschisis. It was found that the frequency of abnormal protein
      patterns in the malformed fetuses is higher by approximately a factor of 2. Two
      proteins showed changes simultaneously in liver, kidney and/or skin of one
      individual fetus. The changes in protein expression probably result from
      mutations induced by the radiation exposure of the embryos at the 1-cell stage of
      prenatal development. We discuss these results in terms of increased mutation
      frequencies in irradiated fetuses with gastroschisis.

PMID- 7516478
TI  - Statistical versus biological significance of genetic toxicity data.

PMID- 7516480
TI  - Strategies and philosophies of genotoxicity testing: highly sophisticated versus
      pragmatic regulatory approaches (reply to Zeiger (1994), strategies and
      philosophies of genotoxicity testing: what is the question?)

PMID- 7516475
TI  - Nuclear localization of the PEP protein tyrosine phosphatase.
AB  - PEP is an intracellular protein tyrosine phosphatase expressed primarily by cells
      of hematopoietic origin that can be divided structurally into a catalytic domain
      and a large carboxy-terminal domain. The carboxy-terminal domain is enriched in
      proline, glutamic acid, serine, and threonine residues (PEST sequences) and
      contains a nonperfect tandem repeat sequence enriched in proline residues and a
      carboxy terminus enriched in basic amino acids. Here we show that PEP is
      diffusely expressed in lymphoid tissues, consistent with expression by many
      different cell types. Analysis of the PEP protein identifies a nuclear
      localization sequence within the extreme carboxy terminus. Transfer of 18 amino
      acids from the carboxy terminus of PEP to beta-galactosidase conferred nuclear
      localization, indicating that this sequence was sufficient for nuclear
      localization. Proteins enriched in PEST sequences are often rapidly degraded.
      However, pulse-chase analysis indicates that PEP has a half-life of greater than
      5 h.

PMID- 7516481
TI  - Propositions in genetic toxicology and their erasure.

PMID- 7516482
TI  - Storage in methanol of smears intended for acridine orange staining.

PMID- 7516483
TI  - Novel types of mutation identified at the hprt locus of human T-lymphocytes.
AB  - The T-cell cloning assay detecting mutations at the hypoxanthine-guanine
      phosphoribosyl transferase (hprt) locus provides a well developed system for
      studying human somatic gene mutation. The hprt mutational spectrum comprises
      missense, nonsense and splice mutations, as well as large structural alterations
      including deletions, duplications and insertions. Only few of the hprt deletions,
      which represent 10-15% of background in vivo mutations in T-cells of adults, have
      been characterized in detail at the genomic level, and the mechanisms involved in
      the majority of hprt structural alterations remain unknown. Illegitimate activity
      of V(D)J recombinase resulting in deletion of hprt exons 2 + 3 has been shown to
      account for 40% of the hprt mutations in T-lymphocytes of human newborns and a
      few percent of the mutations in adults. In this report, novel recombinational
      mechanisms were identified by characterization of two T-cell mutants. One mutant
      derived from a healthy adult was found to have a 3.2-kb genomic insertion in the
      first intron of the hprt gene, and a 369-bp T-cell receptort (TCR) alpha gene
      sequence between exons 1 and 2 of its hprt cDNA. This mutation provides unique
      and direct evidence for illegitimate recombination between the TCR gene and the
      hprt gene in human T-lymphocytes in vivo. Moreover, the mutation identifies a
      novel cDNA sequence for the TCR alpha chain variable region. Another hprt-
      mutant, obtained from a T-cell culture treated with acetaldehyde, showed that
      splice mutation can be caused by a large deletion detectable on Southern blot.
      This 3.4-kb deletion involved both intron 1 and exon 2 sequences and was flanked
      by 5-bp direct repeats. The utilization of a novel cryptic acceptor site in
      intron 1, located far upstream from the lost consensus splice site, resulted in a
      partial inclusion of the intron 1 sequence in the hprt cDNA.

PMID- 7516476
TI  - RNA binding by Sxl proteins in vitro and in vivo.
AB  - Sxl has been proposed to regulate splicing of specific target genes by directly
      interacting with their pre-mRNAs. We have therefore examined the RNA-binding
      properties of Sxl protein in vitro and in vivo. Gel shift and UV cross-linking
      assays with a purified recombinant MBP-Sxl fusion protein demonstrated
      preferential binding to RNAs containing poly(U) tracts, and the protein
      footprinted over the poly(U) region. The protein did not appear to recognize
      either branch point or AG dinucleotide sequences, but an adenosine residue at the
      5' end of the poly(U) tract enhanced binding severalfold. MBP-Sxl formed two
      shifted complexes on a tra regulated acceptor site RNA; the doubly shifted form
      may have been stabilized by protein-protein interactions. Consistent with its
      proposed role in pre-mRNA processing, in nuclear extracts Sxl was found in large
      ribonucleoprotein (RNP) complexes which sedimented significantly faster than bulk
      heterogeneous nuclear RNP and small nuclear RNPs. Anti-Sxl staining of polytene
      chromosomes showed Sxl protein at a number of chromosomal locations, among which
      was the Sxl locus itself. Sxl protein could also be targeted to a new chromosomal
      site carrying a transgene containing splicing regulatory sequences from the Sxl
      gene, following transcriptional induction. After prolonged heat shock, all Sxl
      protein was restricted to the heat-induced puff at the hs93D locus. In contrast,
      a presumptive small nuclear RNP protein was observed at several heat puffs
      following shock.

PMID- 7516484
TI  - Effects of deuterium labeling on azido amino acid mutagenicity in Salmonella
      typhimurium.
AB  - The mutagenic effects of azide (N3-) anion in bacterial test systems require the
      formation of the novel mutagenic metabolite, 3-azido-L-alanine (AZAL). Although
      the mechanism of AZAL-induced mutagenicity is unknown, subsequent bioactivation
      of this metabolite appears likely. Earlier studies have shown that other azide
      containing amino acids are mutagenic as well. In fact, the mutagenic potency of
      the synthetic AZAL homologue, L-2-amino-4-azidobutanoic acid (HomoAZAL), was
      several times that of AZAL. To gain insight into the biochemical processing and
      mutagenicity of azido amino acids in Salmonella typhimurium, several specifically
      deuterium-labeled azido amino acids have been prepared and tested for mutagenic
      potency. In addition, the effect of (aminooxy)acetic acid (AOA) (a potent
      inhibitor of pyridoxal-dependent processes) on AZAL-induced mutagenesis was
      examined. The results showed that 2-deuterium substitution of AZAL resulted in a
      slight increase in mutagenic potency, while AOA treatment resulted in no change
      in AZAL potency. Taken together these findings did not support the involvement of
      pyridoxal-dependent processes in AZAL bioactivation. In contrast, deuterium
      substitution adjacent to the azide group in HomoAZAL and 5-azido-L-norvaline (N3
      Norval) resulted in a large decrease in mutagenic potency when compared to the
      non-deuterium labeled compounds. These observations are consistent with a
      bioactivation mechanism involving rate-limiting C-H bond cleavage in the
      formation of the ultimate mutagen. Moreover, this effect of deuterium labeling
      points to processing of the azide-containing side chain as a key feature in the
      mutagenic activation mechanism.

PMID- 7516485
TI  - Mutagenicity of 5-bromouracil and N6-hydroxyadenine studied by yeast
      oligonucleotide transformation assay.
AB  - The mutagenicity of 5-bromouracil (BrU) and N6-hydroxyadenine (HA) was tested by
      means of the yeast oligonucleotide transformation procedure. BrU-containing
      oligonucleotide was not mutagenic; although two mutants (per 200 micrograms
      oligonucleotide) were obtained, they were attributed to base insertion or base
      substitution at positions different from BrU. This result supports the view that
      BrU mutagenesis is dependent on intracellular nucleotide pool imbalance. In
      contrast, HA-containing oligonucleotide was highly mutagenic; 56 mutants (per 140
      micrograms oligonucleotide) were obtained. Of 21 induced mutants examined, 20 had
      G and one had C at the HA position, a result indicating that HA-->G changes took
      place. To provide back-up evidence, we carried out a general reversion assay for
      base HA using a set of yeast tester strains, and the results showed that HA
      induces exclusively AT-to-GC and GC-to-AT transitions. We conclude that in S.
      cerevisiae HA is a classic base analog mutagen, causing AT-to-GC and GC-to-AT
      transitions by ambiguous base pairing. The present work has clearly demonstrated
      the usefulness of the oligonucleotide transformation procedure for elucidating
      mutagenicity of modified bases.

PMID- 7516487
TI  - Low hprt mRNA levels and multiple hprt mRNA species in 6-thioguanine-resistant
      Chinese hamster cell mutants possessing nonsense mutations.
AB  - Previous studies suggested that many Chinese hamster ovary (CHO) cell hprt
      mutants having point mutations in the protein coding region also have low steady
      state hprt mRNA concentrations. In addition, polymerase-chain reaction (PCR)
      amplification of hprt cDNA synthesized from some of these mutants results in
      multiple products containing deleted exons indicating that these mutants possess
      multiple species of hprt mRNA. In this study, we have used northern blot analysis
      to quantify the concentrations of hprt mRNA in 86 mutants known to possess point
      mutations leading to either missense or nonsense mutations. 28 of 35 nonsense
      mutants (80%), but only 7 of 51 missense mutants (14%), had < 50% of the hprt
      mRNA concentration found in parental CHO cells. Furthermore, all the nonsense
      mutants with premature termination codons in the internal exons of the gene
      (i.e., exons 3, 4, 5, 6 and 7) showed a significant reduction (averages < 16% of
      parental) in the steady-state levels of hprt mRNA, while nonsense mutants with
      termination codons situated in the extreme 5' and 3' regions of the gene had near
      parental hprt mRNA levels. In the same collection of mutants, the proportion of
      mutants producing multiple cDNA PCR products was much greater (18/35) for mutants
      having nonsense mutations than for mutants with missense mutations (2/51). All
      nonsense mutants with mutations in exons 3, 4 and 5 produced multiple species,
      while all those with mutations in exons 7, 8 and 9 produced a single PCR product.
      These results suggest that sequence changes in mammalian genes that affect
      protein chain length can also affect mRNA concentration and the splicing of pre
      mRNA molecules.

PMID- 7516486
TI  - Beta subunit of DNA polymerase III holoenzyme is induced upon ultraviolet
      irradiation or nalidixic acid treatment of Escherichia coli.
AB  - Exposure of Escherichia coli to UV irradiation or nalidixic acid, which induce
      both the SOS and heat shock responses, led to a 3-4-fold increase in the amount
      of the beta subunit of DNA polymerase III holoenzyme, as assayed by Western blot
      analysis using anti-beta antibodies. Such an induction was observed also in a
      delta rpoH mutant lacking the heat shock-specific sigma 32 subunit of RNA
      polymerase, but it was not observed in recA13 or lexA3 mutants, in which the SOS
      response cannot be induced. Mapping of transcription initiation sites of the dnaN
      gene, encoding the beta subunit, using the S1 nuclease protection assay showed
      essentially no induction of transcription upon UV irradiation, indicating that
      induction is regulated primarily at the post-transcriptional level. Analysis of
      translational gene fusions of the dnaN gene, encoding the beta subunit, to the
      lacZ reporter gene showed induction of beta-galactosidase activity upon UV
      irradiation of cells harboring the fusion plasmids. Elimination of a 5' flanking
      DNA sequence in which the dnaN promoters P1 and P2 were located, did not affect
      the UV inducibility of the gene fusions. Thus, element(s) present from P3
      downstream were sufficient for the UV induction. The induction of the dnaN-lacZ
      gene fusions was dependent on the recA and lexA gene products, but not on the
      rpoH gene product, in agreement with the immunoblot analysis. The dependence of
      dnaN induction on the SOS regulators was not mediated via classical repression by
      the LexA repressor, since the dnaN promoter does not contain a sequence
      homologous to the LexA binding site, and dnaN mRNA was not inducible by UV light.
      This suggests that SOS control may be imposed indirectly, by a post
      transcriptional mechanism. The increased amount of the beta subunit is needed,
      most likely, for increased replication and repair activities in cells which have
      been exposed to UV radiation.

PMID- 7516488
TI  - Formation and identification of carcinogenic heterocyclic aromatic amines in
      boiled pork juice.
AB  - Bacterial frameshift mutagens have been found in boiled pork juice. The mutagenic
      compounds of boiled pork juice were purified and analyzed by HPLC. The mutagenic
      fractions corresponding to the peaks of the standard mutagens 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) were
      confirmed by comparison of UV and mass spectra. One gram equivalent of original
      lean ground pork was estimated to contain 4.1 ng of MeIQx, 3.7 ng of IQ, and 1.2
      ng of MeIQ, which accounted for 21.0%, 30.4%, and 38.1%, respectively, of the
      total mutagenicity. The remaining mutagenic fractions might be diMeIQx isomers.
      This will be further confirmed by mass spectrometry in future studies. The amount
      of IQ-type mutagens in boiled pork juice was about 4-fold higher than in broiled
      beef. Furthermore, we investigated the effects of 20 amino acids, three
      monosaccharides, and creatinine on mutagen formation when added to the pork juice
      to elucidate possible precursors leading to the formation of mutagens. Results
      showed that five amino acids (glutamine, tyrosine, glycine, alanine, and
      threonine) and two monosaccharides (ribose and glucose) might participate in
      mutagen formation in boiled pork juice.

PMID- 7516490
TI  - Autoregulation and kinetics of induction of the Rhizobium phaseoli recA gene.
AB  - A fusion between the recA gene of Rhizobium phaseoli and the lacZ gene was
      constructed in vitro and cloned in a mini-Tn5 transposon derivative to obtain
      chromosomal insertions which make it possible to quantitatively examine their
      transcriptional regulation in both R. phaseoli and E. coli. Likewise, and by
      insertion of a spectinomycin-resistance gene cassette into the recA gene of R.
      phaseoli and subsequent marker exchange, a RecA- derivative of this bacterial
      species has been obtained. Analysis of this recA-lacZ fusion showed that it was
      inducible by DNA damage in the RecA+ strain of R. phaseoli but not in the RecA-
      mutant. On the other hand, the recA-lacZ fusion of R. phaseoli was not induced in
      DNA-damaged RecA+ cells of E. coli. Furthermore, the range of UV doses which give
      rise to dose dependence in the induction of its respective recA genes is
      different in R. phaseoli from that in E. coli.

PMID- 7516489
TI  - In vitro and in vivo genotoxicity evaluation of hormonal drugs. II.
      Dexamethasone.
AB  - Genotoxicity evaluation of a widely used glucocorticoid medicine, dexamethasone,
      was undertaken using in vitro and in vivo assays. Analyses of chromosomal
      aberrations, sister-chromatid exchanges (SCEs) in human lymphocytes and
      micronuclei and SCEs in mouse bone marrow showed the drug to be capable of
      attacking the genetic material. However, the Ames/Salmonella assay, both with and
      without S9 mix, did not show any increase in His+ revertants.

PMID- 7516491
TI  - Identification of a specific epitope on the extracellular domain of the LDL
      receptor of Trypanosoma brucei brucei.
AB  - We have previously shown that an antiserum raised against the 86-kDa fragment of
      the low-density lipoprotein-receptor (LDL-receptor) of bloodstream Trypanosoma
      brucei brucei shows extensive cross-reactivity with the mammalian LDL-receptor.
      Here we report on the production and characterisation of 30 monoclonal antibodies
      (mAbs) raised against the same 86-kDa fragment of the T. b. brucei LDL-receptor.
      Of these, only 8 mAbs recognise in an ELISA test the purified (presumably intact)
      145-kDa LDL-receptor. Seven of them also recognise the LDL-receptors isolated
      from rat and rabbit, whereas one mAb (1A9) is specific for the trypanosome LDL
      receptor. A pool of several mAbs inhibits by 90% the specific binding of 125I-LDL
      to trypanosomes at 4 degrees C, but does not interfere with binding of 125I-LDL
      to rat fibroblasts. 125I-mAb 1A9 is efficiently taken up by T. b. brucei at 30
      degrees C and its uptake is inhibited by an excess of unlabelled LDL particles,
      indicating that mAb 1A9 follows the LDL-receptor pathway. Uptake of 125I-mAb 1A9
      by rat fibroblasts is less efficient and is not significantly reduced by an
      excess of unlabelled LDL. MAb 1A9 as well as other pooled mAbs activate rabbit
      complement, leading to lysis of trypanosomes in vitro. We conclude that the T. b.
      brucei LDL-receptor contains at least one specific epitope that is accessible on
      live cells to antibodies and which can activate the complement system.

PMID- 7516492
TI  - Possible localisation of dolichol-dependent mannosyltransferase of Trypanosoma
      brucei to the rough endoplasmic reticulum.
AB  - The glycosylphosphatidylinositol membrane anchor of variant surface glycoprotein
      of the African trypanosome Trypanosoma brucei contains several mannosyl residues
      for which dolichol phosphoryl mannose is supposed to be the precursor; this
      itself is probably synthesised by a dolichol-dependent mannosyltransferase. We
      have characterised and localised a mannosyltransferase activity of T. brucei
      which transfers mannose from GDP-[14C]mannose to exogenously added dolichyl
      phosphate. The enzyme was saturable for both its substrates and had a Km of 7.8
      microM and 3.3 microM, respectively, for dolichyl phosphate and GDP-mannose.
      Mannosyltransferase was labile at 37 degrees C in the presence of Triton X-100,
      but its activity remained constant for at least 60 min at temperatures between 10
      15 degrees C. The enzyme was inhibited by amphomycin and this inhibition was
      potentiated by the presence of 10 mM CaCl2. After subcellular fractionation of
      cell homogenates by differential centrifugation, mannosyltransferase was
      recovered mainly in the microsomal fraction and its distribution was very similar
      to that of RNA, a marker for the rough endoplasmic reticulum. After isopycnic
      centrifugation in a linear sucrose gradient the distribution of
      mannosyltransferase also resembled that of RNA. Both constituents exhibited a
      shift towards lower densities after pre-treatment of microsomal membranes with
      inorganic pyrophosphate, while other membrane markers such as acid phosphatase
      and nucleoside diphosphatase did not. It is concluded that the formation of
      dolichol phosphoryl mannose from GDP-mannose and dolichyl phosphate in T. brucei
      occurs mainly in the rough endoplasmic reticulum.

PMID- 7516493
TI  - Expression and antigenicity of Plasmodium falciparum major merozoite surface
      protein (MSP1(19)) variants secreted from Saccharomyces cerevisiae.
AB  - Four antigenic variants of the 19-kDa carboxy terminal fragment of Plasmodium
      falciparum merozoite surface protein, MSP1 (MSP1(19)), were expressed in
      Saccharomyces cerevisiae as a histidine-tagged, secreted polypeptides
      (rMSP1(19)s). Structural analysis of the rMSP1(19)s indicated that a single amino
      acid change (E to Q) in the first EGF-like domain of the yeast-secreted rMSP1(19)
      proteins caused a significant change in their disulfide bond-dependent
      conformation. The antigenicity of the rMSP1(19)s were qualitatively and
      quantitatively analyzed by direct and competitive binding ELISAs. The data
      indicate that conserved and variant B cell determinants of MSP1(19), as well as
      epitopes that are known targets of protective antibodies, were recreated
      authentically in the rMSP1(19)s. Secretion of histidine-tagged rMSP1(19)s using
      the expression system described may be an efficient and effective means of
      producing a properly folded immunogen for a human vaccine against the blood
      stages of P. falciparum.

PMID- 7516494
TI  - Treating cancer pain.

PMID- 7516495
TI  - Treating cancer pain.

PMID- 7516496
TI  - Treating cancer pain.

PMID- 7516497
TI  - Myelination in the absence of myelin-associated glycoprotein.
AB  - The hypothesis that myelin-associated glycoprotein (MAG) initiates myelin
      formation is based in part on observations that MAG has an adhesive role in
      interactions between oligodendrocytes and neurons. Furthermore, the over- or
      underexpression of MAG in transfected Schwann cells in vitro leads to accelerated
      myelination or hypomyelination, respectively. Here we test this idea by creating
      a null mutation in the mag locus and deriving mice that are totally deficient in
      MAG expression at the RNA and protein level. In adult mutant animals the degree
      of myelination and its compaction are normal, whereas the organization of the
      periaxonal region is partially impaired. Mutant animals show a subtle intention
      tremor. Our findings do not support the widely held view that MAG is critical for
      myelin formation but rather indicate that MAG is necessary for maintenance of the
      cytoplasmic collar and periaxonal space of myelinated fibres.

PMID- 7516498
TI  - Cortical localization of temporal lobe language sites in patients with gliomas.
AB  - In a series of 40 patients undergoing an awake craniotomy for the removal of a
      glioma of the dominant hemisphere temporal lobe, cortical stimulation mapping was
      used to localize essential language sites. These sites were localized to distinct
      temporal lobe sectors and compared with 83 patients without tumors who had
      undergone language mapping for the treatment of intractable epilepsy. In patients
      with and without temporal lobe gliomas, the superior temporal gyrus contained
      significantly more language sites than the middle temporal gyrus. Both patient
      populations also had language sites anterior to the central sulcus in the
      superior temporal gyrus (12-16%). The patients without tumors had significantly
      more language sites in the superior temporal gyrus, compared with the superior
      temporal gyrus of patients with temporal lobe tumors. Multiple variables were
      studied for their effect on preoperative and postoperative language deficits and
      included age, sex, number of language sites, histology, size of the tumor, and
      the distance of tumor resection margins from the nearest language site. The
      distance of the resection margin from the nearest language site was the most
      important variable in determining the improvement in preoperative language
      deficits, the duration of postoperative language deficits, and whether the
      postoperative language deficits were permanent. If the distance of the resection
      margin from the nearest language site was > 1 cm, significantly fewer permanent
      language deficits occurred. Cortical stimulation mapping for the identification
      of essential language sites in patients with gliomas of the dominant hemisphere
      temporal lobe will maximize the extent of tumor resection and minimize permanent
      language deficits.

PMID- 7516499
TI  - Specific bradycardic agents block the hyperpolarization-activated cation current
      in central neurons.
AB  - A class of pharmacologically active substances, known as "specific bradycardic
      agents", exerts a negative chronotropic influence on cardiac activity, which
      heavily relies upon a potent blockade of the hyperpolarization-activated cation
      current in Purkinje fibers. Since the cation conductance activated by
      hyperpolarization seems to represent an ubiquitous class of membrane channel in
      mammals, the present study was undertaken to evaluate the influence of specific
      bradycardic agents [UL-FS 49 (zatebradine) and its derivative DK-AH 268] on
      excitable cells of the central nervous system. Thalamocortical relay neurons of
      the dorsolateral geniculate nucleus, prepared from the guinea-pig thalamus as in
      vitro slices, were taken as model cells, because the significance of the
      hyperpolarization-activated cation current (Ih) for electrogenic activity is well
      documented in these neurons. Local application to relay neurons of the
      bradycardic agents at concentrations in the range 10(-5) to 10(-3) M resulted in
      a significant reduction in the amplitude of the Ih current, in the amplitude of
      the Ih activation curve, and in the slope of the fully activated Ih I/V
      relationship. The bradycardic agents did not affect the instantaneous currents
      with no contribution of Ih, the time course of Ih activation, the voltage range
      of Ih activation, or the reversal potential of Ih. The inhibitory effect was
      critically dependent upon Ih activation with open Ih channels probably
      representing a sufficient condition for blockade. Significant recovery from block
      did not occur. Under current-clamp conditions, slow anomalous inward
      rectification of the membrane in the hyperpolarizing direction was blocked, and
      the resting input resistance increased by 30% associated with a negative shift
      (average 10 mV) of the membrane potential into a region of Ca(2+)-mediated burst
      activity. Parameters of electrophysiological activity outside the range of Ih
      activation were not significantly affected. These data indicate a selective and
      use-dependent blockade exerted by specific bradycardic substances on the
      conductance underlying Ih with no alteration in the gating properties. In view of
      the existence of hyperpolarization-activated cation conductances in neurons from
      various regions of the mammalian peripheral and central nervous systems, the
      results of the present study remind us of possible neuronal side-effects of
      bradycardia-producing agents.

PMID- 7516500
TI  - Progressive degeneration of nigrostriatal dopamine neurons following
      intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde
      tracing and immunocytochemical study in the rat.
AB  - In order to develop a rodent model displaying a progressive degeneration of the
      dopamine neurons of the substantia nigra, we bilaterally injected the tracer
      substance FluoroGold into the terminal field of the nigrostriatal projection,
      i.e. the striatum. One week later, rats received unilateral injections of 20
      micrograms 6-hydroxydopamine into one of the two striatal tracer deposits. Groups
      of animals were killed one, two, four, eight and 16 weeks later. Ipsilateral to
      the lesion there was a progressive loss of FluoroGold-labelled nigral cells, with
      cell counts dropping from 96% of the contralateral side at one week to 59% at two
      weeks, 35% at four weeks, 23% at eight weeks and down to 15% at 16 weeks.
      Labelled nigral neurons ipsilateral to the lesion showed a moderate to marked
      atrophy at all investigated time points. The number of tyrosine hydroxylase
      immunoreactive cells was decreased to 83% of contralateral at one week, 39% at
      two weeks, 44% at four weeks, 34% at eight weeks and 52% at 16 weeks postlesion.
      Rhodamine fluorescence immunocytochemistry showed that the proportion of
      surviving ipsilateral fluorogold-labelled cells displaying immunoreactivity for
      tyrosine hydroxylase was 69% at one week postlesion, 51% at two weeks, 63% at
      four weeks, 69% at eight weeks and 76% at 16 weeks. We conclude that injection of
      6-hydroxydopamine into the terminal field of nigral dopaminergic neurons causes a
      progressive degeneration of these cells, starting between one and two weeks after
      lesion and continuing over eight to 16 weeks. This degeneration is preceded, and
      accompanied by, cellular atrophy and a partial loss of marker enzyme expression,
      thus yielding an animal model which mimics the degenerative processes in
      Parkinson's disease more closely than the animal models available so far. The
      present model may be helpful in investigating the in vivo effects of putative
      neuroprotective agents and neurotrophic factors.

PMID- 7516501
TI  - Nitric oxide synthase immunoreactivity in rat pontine medullary neurons.
AB  - Nitric oxide synthase immunoreactivity was detected in neurons and fibers of the
      rat pontine medulla. In the medulla, nitric oxide synthase-positive neurons and
      processes were observed in the gracile nucleus, spinal trigeminal nucleus,
      nucleus of the solitary tract, dorsal motor nucleus of the vagus, nucleus
      ambiguus, medial longitudinal fasciculus, reticular nuclei and lateral to the
      pyramidal tract. In the pons, intensely labeled neurons were observed in the
      pedunculopontine tegmental nucleus, paralemniscal nucleus, ventral tegmental
      nucleus, laterodorsal tegmental nucleus, and lateral and medial parabrachial
      nuclei. Labeled neurons and fibers were seen in the interpeduncular nuclei,
      dorsal and median raphe nuclei, central gray and dorsal central gray, and
      superior and inferior colliculi. Double-labeling techniques showed that a small
      population (< 5%) of nitric oxide synthase-positive neurons in the medulla also
      contained immunoreactivity to the aminergic neuron marker tyrosine hydroxylase.
      The majority of nitric oxide synthase-immunoreactive neurons in the dorsal and
      median raphe nuclei were 5-hydroxytryptamine-positive, whereas very few 5
      hydroxytryptamine-positive cells in the caudal raphe nuclei were nitric oxide
      synthase-positive. Virtually all nitric oxide synthase-positive neurons in the
      pedunculopontine and laterodorsal tegmental nuclei were also choline
      acetyltransferase-positive, whereas nitric oxide synthase immunoreactivity was
      either low or not detected in choline acetyltransferase-positive neurons in the
      medulla. The results indicate a rostrocaudal gradient in the intensity of nitric
      oxide synthase immunoreactivity, i.e. it is highest in neurons of the tegmentum
      nuclei and neurons in the medulla are less intensely labeled. The majority of
      cholinergic and serotonergic neurons in the pons are nitric oxide synthase
      positive, whereas the immunoreactivity was either too low to be detected or
      absent in the large majority of serotonergic, aminergic and cholinergic neurons
      in the medulla.

PMID- 7516503
TI  - The distribution of nitric oxide synthase immunoreactivity in the human brain.
AB  - Nitric oxide is a free radical which is produced in the brain and is thought to
      be the first of a new class of neural messenger molecules. It is postulated to
      act by inducing an increase in cyclic guanosine monophosphate levels in target
      cells. The neuronal isoform of nitric oxide synthase, the enzyme responsible for
      the calcium-dependent synthesis of nitric oxide from L-arginine, has been
      purified from brain homogenate. Using a specific polyclonal antibody, we have
      localized brain nitric oxide synthase to the cytosol of discrete neuronal
      subpopulations and glial elements. These include non-pyramidal cells in the
      cerebral cortex, pyramidal and non-pyramidal cells of the hippocampus, aspiny
      neurons of the corpus striatum, basket, Purkinje and granule cells in the
      cerebellum and neurons of various brain stem nuclei. The localization of nitric
      oxide-producing neurons in morphologically different and neurochemically diverse
      cell types suggests a widespread neuromodulatory role for nitric oxide in the
      central nervous system of man.

PMID- 7516502
TI  - Rat spinal cord neurons contain nitric oxide synthase.
AB  - We describe the distribution and characteristics of nitric oxide synthase
      containing neurons in rat spinal cord using a polyclonal affinity-purified
      antibody against rat cerebellar nitric oxide synthase. Numerous neurons were
      stained throughout the entire rostrocaudal extent of the spinal cord. Cell
      bodies, dendrites and axons stained in a uniform manner. Nitric oxide synthase
      immunoreactivity was intense in neurons of laminae I-IV and X throughout the
      entire spinal cord. Neurons in the intermediolateral cell column of the thoracic
      and lumbar spinal cord were also intensely stained for nitric oxide synthase. The
      sacral cord demonstrated substantial nitric oxide synthase immunostaining within
      lamina VII. For the entire cord, scattered neurons in laminae V, VI, VII, and
      VIII were weakly positive. In addition, punctate nitric oxide synthase staining
      throughout laminae I, III and surrounding some large motor neurons in the ventral
      horn suggested the presence of nitric oxide synthase at synapses. Axons and
      dendritic terminals located in the gray and white matter were also stained. The
      majority of nitric oxide synthase positive neurons in the intermediolateral cell
      column were double-labelled by subcutaneously injected FluoroGold confirming that
      these cells were preganglionic autonomic neurons. Most NADPH-diaphorase-stained
      neurons were also nitric oxide synthase-positive. The distribution of nitric
      oxide synthase-containing neurons in spinal cord suggests that nitric oxide plays
      a role in spinal cord neurotransmission including: preganglionic sympathetic and
      parasympathetic, somatosensory, visceral sensory and possibly motor pathways. In
      particular, the autonomic nervous system appears enriched with nitric oxide
      synthase immunoreactivity. The precise role of each neuron type remains to be
      demonstrated in physiologic and pathophysiologic paradigms.

PMID- 7516504
TI  - The age-related increase in galanin binding sites in the rat brain correlates
      with behavioral impairment.
AB  - The regional distribution of [125I]galanin specific binding sites was determined
      in young (three- to four-month-old), 14-15-month-old and aged (26-27-month-old)
      male Sprague-Dawley rats, previously tested for their performances in the Morris
      water-maze task, using the radioautographic method on brain sections. A
      significant increase in specific binding was observed in piriform and entorhinal
      cortex, ventral subiculum, and dorsal dentate gyrus in the aged rats, whereas no
      significant changes were observed in dorsal subiculum, amygdala, septal area and
      various subcortical structures. The area-specific regional increase in specific
      binding density in aged rats was significantly correlated with the impairment of
      the behavioral performance in the Morris water-maze task. The change in
      [125I]galanin specific binding was a result of an increase in the number of
      galanin binding sites, but not of an increase in affinity.

PMID- 7516505
TI  - The organization of midbrain projections to the ventral striatum in the primate.
AB  - Because the dopaminergic neurons of the midbrain form a continuum, boundaries
      between the ventral tegmental area, substantia nigra pars compacta, and
      retrorubral area are difficult to distinguish in the primate. Therefore,
      dopaminergic neurons have been subdivided into more readily discernible dorsal
      and ventral tiers. The projections from these dorsal and ventral tier neurons of
      the ventral mesencephalon to the ventral striatum were labeled by injections of
      horseradish peroxidase conjugated to wheatgerm agglutinin and Lucifer Yellow
      conjugated to dextran amines into different regions of the nucleus accumbens, the
      ventral caudate nucleus, and the rostral, ventral putamen in the primate. Neurons
      projecting to the ventral striatum are not topographically organized in the
      ventral mesencephalon. Retrogradely labeled neurons are found in the medial
      densocellular zone of the ventral tier following injections into all regions of
      the ventral striatum except the ventromedial shell region of the nucleus
      accumbens. These medial nigral neurons have diverging projections throughout the
      mediolateral extent of the ventral striatum. In addition, neurons of the dorsal
      tier project to all ventral striatal regions examined. Notably, neurons
      projecting to the shell region of the nucleus accumbens are limited to the dorsal
      tier, throughout the rostrocaudal extent of the substantia nigra. Both dorsal and
      ventral tier neurons innervate the ventral striatum. Not only do neurons of the
      ventral tegmental area project to the ventral striatum, but also many of the pars
      compacta. The projections to the shell region of the nucleus accumbens are more
      restricted, suggesting that the dopaminergic regulation of this accumbens
      subterritory is distinct from the rest of the ventral striatum.

PMID- 7516506
TI  - The organization of midbrain projections to the striatum in the primate:
      sensorimotor-related striatum versus ventral striatum.
AB  - In order to examine the organization of nigrostriatal projections in the primate,
      the retrograde tracers Lucifer Yellow conjugated to dextran amines and
      horseradish peroxidase conjugated to wheatgerm agglutinin were injected into
      different regions of the dorsolateral and ventral striatum. Based on the
      topography of cortical inputs to the striatum, the dorsolateral striatum is
      associated with the motor system, and the ventral striatum is related to the
      limbic system. Our results indicate that although midbrain neurons projecting to
      the ventral and dorsolateral striatum are mostly separate, there are neurons
      projecting to these different striatal territories that overlap in the medial
      substantia nigra. The dopaminergic neurons of the ventral mesencephalon can be
      subdivided into dorsal and ventral tiers that include the cells of the ventral
      tegmental area, the substantia nigra pars compacta, and the retrorubral area.
      Neurons projecting to the ventral striatum are found in both the dorsal and
      ventral tiers. A large number of neurons occupying the medial densocellular zone
      of the ventral tier are labeled following injections into different regions of
      the ventral striatum. Neurons projecting to the sensorimotor-related striatum are
      derived almost exclusively from the ventral tier. Many of these neurons are
      located very ventrally in the substantia nigra, where clusters of neurons invade
      the pars reticulata. In addition, labeled neurons are found throughout the
      mediolateral extent of the densocellular zone of the pars compacta. Notably,
      neurons are labeled in the medial densocellular zone following injections into
      the dorsolateral and ventral striatum. Mesencephalic neurons projecting to
      different striatal territories are distinct in that dorsal tier neurons mainly
      innervate the ventral striatum, whereas the ventral columns of neurons in the
      ventral tier innervate the sensorimotor-related striatum. Thus, the dopaminergic
      regulation of the sensorimotor-related striatum and the ventral striatum may be
      different. However, a subgroup of dopaminergic neurons in the medial
      densocellular zone projects to both striatal territories. Such divergent
      projections may allow the substantia nigra to serve as a link, connecting
      different striatal territories, via their connections with the substantia nigra.

PMID- 7516507
TI  - Development of Purkinje cell bodies and processes with basic fibroblast growth
      factor-like immunoreactivity in the rat cerebellum.
AB  - The development of basic fibroblast growth factor-like immunoreactivity was
      investigated in the nuclei, cell bodies and processes of Purkinje cells with
      attention to basic fibroblast growth factor-containing neuronal input to the deep
      cerebellar nuclei. Immunoblot analysis with the use of the antisera against basic
      fibroblast growth factor revealed that crude homogenate of the developing rat
      cerebellum exhibits a main band with the same molecular weight (18,000 mol. wt)
      as basic fibroblast growth factor in all the postnasal stages examined.
      Cerebellar cells were not labeled with the antisera during embryonic life. Under
      light microscopy, basic fibroblast growth factor-like immunoreactivity was
      detected initially in cortical cells located close to deep cerebellar fissures of
      the newborn rat but not in superficial cortical regions. It was difficult to
      determine whether or not they are Purkinje cells at the fusiform stage. On
      postnatal day 7, immunoreactive Purkinje cells were identified throughout the
      cerebellar cortex, and they expressed basic fibroblast growth factor-like
      immunoreactivity mainly in the apical cytoplasm and proximal dendrites. From
      postnatal day 14 to postnatal day 28, basic fibroblast growth factor-like
      immunoreactivity was noted not only throughout the cytoplasm of Purkinje cells
      but also in the nuclei of the immunopositive cells. Our statistical analysis
      showed that Purkinje cells with nuclear immunoreaction peaked on postnatal day
      21. At these stages, nerve fibers immunoreactive for basic fibroblast growth
      factor were numerous in the cerebellar medulla and deep cerebellar nuclei. After
      postnatal day 42, Purkinje cells with intense immunoreactivity in the nuclei
      showed a marked decrease in number, and immunoreactive structures were
      distributed in the cerebellum in a fashion similar to that in adult rats.
      Electron microscopy demonstrated that immunoreactivity was located mainly in the
      apical cytoplasm of Purkinje cells on postnatal day 7 and throughout the
      cytoplasm and in the nuclear euchromatin from postnatal day 14 to postnatal day
      28, as was expected from light-microscopic observations. Immunoreactivity, even
      though distributed diffusely in the cytoplasm, was absent from the lumen of
      endoplasmic reticulum and mitochondria. A small population of Purkinje cell axon
      terminals forming synapses with the soma and dendrites of deep cerebellar nucleus
      neurons began to express basic fibroblast growth factor on postnatal day 21. This
      is much later than the starting age for synaptogenesis between Purkinje cells and
      deep cerebellar nucleus neurons. The age-dependent changes in the localization of
      basic fibroblast growth factor within Purkinje cell nucleus, soma and processes
      suggest a complex transport system of this factor within Purkinje cells during
      postnatal development.

PMID- 7516510
TI  - Electrophysiological and morphological differentiation of chandelier and basket
      cells in the rat hippocampal formation: a study combining intracellular recording
      and intracellular staining with biocytin.
AB  - Using standard intracellular recording techniques 38 nonpyramidal cells or
      interneurons have been sampled in hippocampal slices of the rat. Among 38
      physiologically identified interneurons, all 27 cells labeled with biocytin were
      morphologically demonstrated to be nonpyramidal and nongranule cells. The vast
      majority of these cells showed typical fast spiking discharges, i.e., a shorter
      duration action potential followed by a brief but prominent after
      hyperpolarisation potential without frequency adaptation in response to prolonged
      depolarizing current injection. However, 4 cells clearly exhibited frequency
      adaptation. Based on their axonal arborizations, the former group included basket
      interneurons innervating the principle cell body layers and axodendritic
      interneurons projecting to the molecular layer of the dentate gyrus; whereas the
      latter 4 cells belonged to chandelier interneurons selectively terminating the
      axon initial segments of principle cells. These results support the notion that
      interneurons in the hippocampal formation are heterogeneous with respect to their
      morphology and electrophysiological characteristics, suggesting that the
      electrophysiological behavior of hippocampal interneurons may be associated with
      their functional activities.

PMID- 7516509
TI  - Sensory ganglia as a target of autonomic and sensory nerve fibres in the guinea
      pig.
AB  - The distribution of neuropeptide- (neuropeptide Y, substance P, vasoactive
      intestinal peptide) and catecholamine-synthesizing enzyme-immunoreactive axons in
      guinea-pig trigeminal, nodose, and cervical dorsal root ganglia was studied by
      double-labelling immunofluorescence in controls and after extirpation of either
      the cervical sympathetic trunk or the stellate ganglion; tyrosine hydroxylase-
      and dopamine-beta-hydroxylase-immunoreactive terminals in dorsal root ganglia
      were ultrastructurally investigated. Six neurochemically identifiable axons
      innervated the trigeminal ganglion, five kinds were found in the nodose and
      dorsal root ganglia. Two of them (catecholaminergic with and without neuropeptide
      Y) were of sympathetic origin and, besides their termination at arteries,
      provided a direct innervation of capsule cells of the trigeminal and cervical
      dorsal root ganglia facing the subarachnoid space. Varicosities which were
      interpreted as being of sensory origin were equally numerous in all ganglia,
      whereas those being likely of parasympathetic origin decreased in numbers from
      the trigeminal to the dorsal root and nodose ganglia. It is concluded that the
      sensory ganglia are the target of postganglionic sympathetic, parasympathetic and
      primary afferent neurons, each of which are specifically organized with respect
      to the neurochemical phenotype and inter- and intraganglionic distribution. Among
      other targets, these "nervi gangliorum" appear to be intimately linked to the
      ganglionic capsular cells and meningeal sheaths facing the liquor spaces.

PMID- 7516508
TI  - Neuropeptide expression by newborn and adult rat sensory neurons in culture:
      effects of nerve growth factor and other neurotrophic factors.
AB  - Adult rat dorsal root ganglion sensory neurons in culture require nerve growth
      factor for synthesis of substance P and calcitonin gene-related peptide but
      express vasoactive intestinal peptide independently of nerve growth factor. In
      contrast, the same neurons from newborn rats do not express detectable vasoactive
      intestinal polypeptide when cultured with nerve growth factor. To further explore
      the mechanisms regulating neuropeptide expression in these cells, I compared the
      effects of nerve growth factor, brain-derived neurotrophic factor, neurotrophin
      3, ciliary neurotrophic factor and leukaemia inhibitory factor on substance P,
      calcitonin gene-related peptide, vasoactive intestinal polypeptide and
      somatostatin expression in rat dorsal root ganglion cultures. As with neurons
      from adult animals, newborn rat sensory neurons required nerve growth factor for
      synthesis of substance P and calcitonin gene-related peptide. This effect was
      independent of neuronal survival since most neurons capable of expressing these
      peptides appeared to survive without added neurotrophic factors. Neurons
      surviving in the absence of nerve growth factor also expressed vasoactive
      intestinal polypeptide, suggesting that nerve growth factor suppresses vasoactive
      intestinal polypeptide expression in immature neurons. However, nerve growth
      factor withdrawal after eight days' culture failed to cause vasoactive intestinal
      polypeptide induction which therefore appears to depend on other factors also.
      Neither ciliary neurotrophic factor nor leukaemia inhibitory factor affected
      peptide levels when used alone, but both inhibited nerve growth factor-stimulated
      expression of substance P and calcitonin gene-related peptide in adult rat
      neurons. They also stimulated vasoactive intestinal polypeptide expression in
      newborn rat neurons in the presence of nerve growth factor but not to such high
      levels as those seen under conditions of nerve growth factor deprivation. Neither
      brain-derived neurotrophic factor nor neurotrophin-3 affected peptide expression
      significantly. Somatostatin was defected in adult rat neurons, but was unaffected
      by neurotrophic factors. No somatostatin was detected in newborn rat neurons.
      These results suggest that in immature animals at least, the increased expression
      of vasoactive intestinal polypeptide seen in sensory neurons following peripheral
      nerve injury in vivo, could result from deprivation of target-derived nerve
      growth factor in combination with increased availability of ciliary neurotrophic
      factor or leukaemia inhibitory factor from the injured nerve.

PMID- 7516511
TI  - Substance P produces an inward current by suppressing voltage-dependent and 
      independent K+ currents in bullfrog primary afferent neurons.
AB  - A whole-cell patch-clamp study was carried out to examine the effect of substance
      P (SP) on the excitability of neurons in bullfrog dorsal root ganglia (DRG). SP
      (3 nM to 1 microM) produced an inward current associated with decreased membrane
      conductance at voltage range between -10 and -130 mV. Neurokinin A (NKA) and
      neurokinin B (NKB) also produced the inward current in DRG cells; the rank order
      of agonist potency was NKA = SP much greater than NKB. An antagonist for SP
      receptors, [D-Arg1, D-Trp7,9, Leu11]SP, did not prevent the response to SP. SP (3
      nM to 1 microM) suppressed the voltage-dependent non-inactivating K+ current, the
      M-current (IM) by reducing the maximum M-conductance. A voltage-independent
      background K+ current, IK(B), could be recorded at a hyperpolarizing voltage (<
      or = -60 mV) from DRG neurons. SP (3 nM to 1 microM) produced the inward current
      associated with decreased IK(B) at a holding potential more negative than -60 mV.
      The SP-induced inward current reversed its polarity at the equilibrium potential
      for K ions. Intracellular dialysis with Cs+ blocked the SP-induced responses.
      Depletion of intracellular ATP reduced SP-induced inward current. These results
      suggest that the SP-induced inward current was due to suppression of both the IM
      and IK(B) that are regulated by intracellular activity of ATP in bullfrog DRG
      neurons.

PMID- 7516513
TI  - Fractured jaw--your role after surgery.

PMID- 7516512
TI  - Involvement of substance P and excitatory amino acids in aversive behavior
      elicited by intrathecal capsaicin.
AB  - The rat given an intrathecal injection of capsaicin (0.3-10 nmol/rat) through a
      lumbar puncture showed biting or licking the tail and hind paws. The substance P
      antagonist, CP-96,345 (3 nmol/rat), co-administered intrathecally with capsaicin
      (10 nmol/rat), caused a significant inhibition of the behavioral responses to
      capsaicin (10 nmol/rat). When co-administered intrathecally with the NMDA
      antagonist, 2-amino-5-phosphonovaleric acid (APV, 10 nmol/rat), the capsaicin (10
      nmol/rat) -induced behavioral responses were significantly inhibited. A co
      administration of the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX, 10 nmol/rat), resulted in a significant reduction of the behavioral
      responses produced by capsaicin (10 nmol/rat). Administration of the combination
      of two antagonists (CP-96,345 and either APV or CNQX, or APV and CNQX) more
      markedly inhibited the behavioral responses to capsaicin (10 nmol/rat) than when
      either antagonist was co-administered with capsaicin. The results suggest that
      aversive behaviors induced by intrathecal capsaicin are mediated not only by the
      activation of NK-1 receptors but also by that of NMDA and non-NMDA receptors.

PMID- 7516514
TI  - Fetal oculocerebrorenal syndrome of Lowe associated with elevated maternal serum
      and amniotic fluid alpha-fetoprotein levels.
AB  - OBJECTIVE: To report an association between fetal oculocerebrorenal syndrome of
      Lowe and elevations in maternal serum alpha-fetoprotein (MSAFP) and amniotic
      fluid alpha-fetoprotein (AFAFP). METHODS: Case 1 was identified during routine
      MSAFP screening. Cases 2-5 were identified through review of a data base of
      individuals with oculocerebrorenal syndrome enrolled at the National Institutes
      of Health. To estimate the frequency of this association, only those whose
      mothers would have been in the early second trimester from February 1987 to
      August 1993 were enumerated. The MSAFP was assumed to be normal unless explicitly
      reported or unless information outside the data base confirmed that MSAFP was not
      determined. RESULTS: An elevated MSAFP (2.5 multiples of the median [MoM] or
      greater) was detected in five of 20 pregnancies with a fetus affected by
      oculocerebrorenal syndrome. Maternal serum alpha-fetoprotein was greater than 5.0
      MoM in three pregnancies undergoing amniocentesis, and all had an elevated AFAFP
      without significant acetylcholinesterase activity. No abnormalities were found by
      ultrasound, and there was no other cause of elevated AFP identified postnatally.
      Family history was positive in three of the five cases. The mothers were carriers
      in four of the five cases, whereas the fifth case appeared to be a spontaneous
      mutation. CONCLUSIONS: Elevated MSAFP and AFAFP appear to occur at a higher than
      expected frequency in pregnancies carrying an oculocerebrorenal syndrome fetus.
      The mechanism of elevation of AFP may be related to fetal renal tubular
      dysfunction. A directed interview, focusing on a maternal family history of male
      relatives with unexplained mental retardation, early institutionalization, or
      congenital rubella, is appropriate with unexplained MSAFP elevations and,
      particularly, with unexplained AFAFP elevations without acetylcholinesterase
      activity.

PMID- 7516515
TI  - The relation between human fetal growth and fetal blood levels of insulin-like
      growth factors I and II, their binding proteins, and receptors.
AB  - OBJECTIVE: To determine the relation between normal human fetal growth and the
      levels of insulin-like growth factors (IGF-I, IGF-II), their receptors, and IGF
      binding protein-3 (IGFBP-3) in both the maternal and fetal compartments. METHODS:
      Serum samples were obtained from normal pregnant women (n = 52) and their fetuses
      (n = 32) via funipuncture at 21-34 weeks' gestation (mean 29 +/- 4.3) and from
      term neonates (n = 20) between 38-41 weeks (mean 39 +/- 0.9). Neonates were
      divided into two groups: the "large" group, whose weights were above the mean for
      gestational age, and the "small" group, whose weights were below the mean.
      Aliquots of amniotic fluid (AF) and serum samples were analyzed for levels of IGF
      I, IGF-II, and IGFBP-3. Type 1 IGF receptors were assayed from placental extracts
      of first-trimester elective abortions and from term deliveries. RESULTS: Fetal
      IGF-I serum levels remained stable throughout most of pregnancy until 34 weeks'
      gestation (56 +/- 30 ng/mL). Thereafter, IGF-I increased significantly until term
      (79 +/- 8 ng/mL) (P < .05). Fetal IGF-II levels were relatively unchanged from 23
      weeks to term except for a significant increase at 34 weeks. Fetal serum levels
      of IGFBP-3 averaged 0.8 +/- 0.05 microgram/mL up to 30 weeks' gestation and then
      increased slightly toward term, at 0.96 +/- 0.05 micrograms/mL. At term, the
      levels of IGF-I and IGF-II in the AF were not different from the levels in the
      neonatal serum, but were lower (P < .005) than those in maternal blood. All
      placental tissue obtained from first-trimester terminations of pregnancy assayed
      positive for IGF type 1 receptors. There was a direct correlation between
      neonatal weight and the levels of IGF-I (P < .02), but not with the levels of IGF
      II. There were no significant correlations between newborn weights and IGFBP-3,
      or maternal serum levels of IGF-I and IGF-II. Amniotic fluid IGF-I and IGF-II
      levels were almost similar to fetal serum levels. CONCLUSION: These data
      demonstrate the presence of type 1 receptors and the bioavailability of IGF-I,
      IGF-II, and IGFBP-3 throughout pregnancy. Insulin-like growth factor-I is shown
      to be adjunctively and directly associated with fetal size in normal pregnancies.
      The precise role that IGFs play in deviant fetal growth or whether IGFs can be
      used to treat reduced fetal growth remains unknown and awaits further
      investigation.

PMID- 7516516
TI  - Clinicopathologic features of surgically excised choroidal neovascular membranes.
AB  - PURPOSE: The purpose of this study is a descriptive correlation of the clinical,
      fluorescein angiographic, and pathologic features in a large series of patients
      who underwent surgical removal of choroidal neovascular membranes. METHODS: The
      patients' clinical data were recorded for each surgically removed choroidal
      neovascular membrane received in the authors' laboratory. Fluorescein
      angiographic characteristics of the membranes, including well-demarcated versus
      poorly demarcated preoperative appearance, postoperative choroidal atrophy, and
      membrane recurrence, were recorded whenever possible. The pathologic features of
      the membranes, including cellular and extracellular constituents, were determined
      on light and electron microscopic examination. RESULTS: A total of 123 membranes
      were studied. Underlying diseases in decreasing order of frequency were age
      related macular degeneration, ocular histoplasmosis syndrome, myopia, idiopathic
      and pattern dystrophy. The cellular and extracellular constituents of the
      membranes were similar, regardless of underlying disease, with the exception of
      basal laminar deposit, seen almost exclusively in age-related macular
      degeneration. Well-demarcated membrane components were localized with a central
      subretinal pigment epithelium fibrovascular core. Poorly demarcated membranes
      were represented by a subneurosensory retinal (breakthrough) component, although
      most of these membranes had associated retinal pigment epithelium. Fragments of
      Bruch's membrane were common in specimens from patients with postoperative
      choroidal atrophy, and there was generally a lack of vascular channels in
      membranes that led to recurrence. CONCLUSIONS: This study suggests that choroidal
      neovascular membranes represent a stereotypic, nonspecific response, regardless
      of underlying disease. Most membranes are subretinal pigment epithelium, and what
      is recognized angiographically as a subneurosensory retinal component contains
      associated retinal pigment epithelium in most instances. Fragments of Bruch's
      membrane in the specimen correlate with postoperative choroidal atrophy. Lack of
      vascular channels in the surgical specimen may correlate with a risk for
      postoperative membrane recurrence.

PMID- 7516517
TI  - Histopathologic examination of vascular patterns in subfoveal neovascular
      membranes.
AB  - BACKGROUND: Subfoveal neovascular membranes cause significant visual loss in age
      related macular degeneration (AMD) and the ocular histoplasmosis syndrome. The
      frequency of post-laser treatment persistence or recurrence of subfoveal
      membranes in AMD is as high as 51%. The reason for the high incidence of failure
      after laser treatment is unknown. The authors performed a histopathologic study
      of subfoveal membranes to determine the distribution of blood vessels within the
      neovascular complex, and to see if the blood vessel pattern would provide insight
      into the reason for laser treatment failure. METHODS: The authors used light
      microscopy to examine serial sections of subfoveal membranes from six patients (4
      with AMD, 2 with the ocular histoplasmosis syndrome). The data from this
      examination were used to create detailed two-dimensional vascular maps of each
      membrane. RESULTS: The authors found that subfoveal membranes from patients with
      AMD and the ocular histoplasmosis syndrome, whether occurring de novo or after
      laser treatment, have a nonuniform distribution of blood vessels, and that large
      areas which include the membrane margin may be avascular. CONCLUSIONS: Using
      current laser treatment protocols, it is likely that avascular or poorly perfused
      peripheral areas of the neovascular complex would be left untreated after laser
      photocoagulation. Partial treatment of the neovascular complex may contribute to
      the high rate of post-laser treatment persistence or recurrence of subfoveal
      membranes.

PMID- 7516519
TI  - HIV transmission and healthcare settings.

PMID- 7516518
TI  - Hyperopia and choroidal neovascularization.

PMID- 7516520
TI  - Straight talk about AIDS. Dr. Bruce Dixon addresses PDA at Scientific Session.

PMID- 7516521
TI  - Discrimination & confidentiality issues and the HIV-infected patient.

PMID- 7516523
TI  - Cooking for life nutrition and AIDS.

PMID- 7516522
TI  - Diagnosis & treatment of common oral manifestations associated with HIV disease.

PMID- 7516525
TI  - Back in a heartbeat.

PMID- 7516524
TI  - Image and substance: reflections on the proposed restructuring at the ADA.

PMID- 7516526
TI  - OSHA bloodborne pathogens standard: a guide to dental practice compliance.

PMID- 7516527
TI  - Voluntary OSHA inspection and evaluation: a case report.

PMID- 7516528
TI  - The dental laboratory and infection control.

PMID- 7516529
TI  - Keynote speaker Maury Kelley talks about consumer needs.

PMID- 7516530
TI  - Ethics and professionalism no easy answers.

PMID- 7516531
TI  - Air-driven dental handpieces: selection and infection control.

PMID- 7516532
TI  - Tuberculosis: a born-again adversary for the dental health care worker.

PMID- 7516533
TI  - Antinociception following implantation of mouse B16 melanoma cells in mouse and
      rat spinal cord.
AB  - B16 F1C29 melanoma cells, which are thought to contain and release
      catecholamines, were implanted in mouse and rat spinal subarachnoid space. B16
      F1C29 cell implants augmented the antinociceptive effect of morphine in tail
      flick test, and this interaction was blocked by either the alpha 2-adrenergic
      antagonist idazoxan or the opioid antagonist naloxone. B16 F1C29 cell implants
      also augmented the antinociceptive effect of the catecholamine re-uptake blocker
      desipramine. Substance P-induced biting and scratching behaviors were inhibited
      in mice receiving B16 F1C29 cell implants, and this effect of B16 F1C29 cell
      implants was blocked by the alpha 2-adrenergic antagonist idazoxan. Mice
      receiving B16 F1C29 cell implants showed tolerance to intrathecal administration
      of the alpha 2-adrenergic agonist UK 14304. These results suggest that B16 cell
      implant-induced antinociception was mediated by catecholamines secreted from the
      cell implants and acting at spinal alpha 2-adrenergic receptors. Spinal
      implantation of catecholamine-releasing cells may provide an alternative approach
      for the therapy of chronic intractable pain and a useful model to study alpha 2
      adrenergic receptor tolerance.

PMID- 7516534
TI  - Porphyromonas gingivalis lipopolysaccharide stimulation of human monocytes:
      dependence on serum and CD14 receptor.
AB  - The purpose of this study was to investigate factors influencing the ability of
      lipopolysaccharide (LPS) derived from Porphyromonas gingivalis to elicit
      secretion of tumor necrosis factor-alpha (TNF alpha) from human monocytes
      (adherent mononuclear cells). The results indicate that P. gingivalis LPS
      stimulation of TNF alpha from monocytes is comparable to LPS from Escherichia
      coli. Both LPS, although structurally different, increased TNF alpha secretion in
      a dose-dependent manner. In serum-free conditions, TNF alpha secretion was
      relatively low, but it dramatically increased at human serum concentrations as
      low as 1%. Maximal secretion was observed in the presence of 10% serum, with a
      slight decrease at higher serum concentrations. The CD14 molecule is a putative
      monocyte LPS receptor. When cells were pre-incubated with a blocking monoclonal
      antibody (My4) to CD14, TNF alpha-mRNA accumulation and TNF alpha secretion were
      reduced to control levels at LPS concentrations of up to 10 ng/ml. At higher LPS
      concentrations, the blocking effect was only partial, in spite of 50-fold excess
      antibody concentration. The blocking effect was observed only in the presence of
      serum. The effect of the CD14 antibody was dose-dependent with saturation at 2.5
      micrograms/ml. The results suggest that CD14 is one of the major receptors for P.
      gingivalis LPS but highlight the necessity to investigate other cell-surface
      receptors mediating P. gingivalis-LPS interactions. These interactions are
      believed to be important in the pathogenesis of periodontal destruction.

PMID- 7516535
TI  - Schistosoma mansoni: immunolocalization of two different fucose-containing
      carbohydrate epitopes.
AB  - We have used two monoclonal antibodies, 128C3/3 and 504B1, to immunolocalize
      their carbohydrate epitopes in different developmental stages of Schistosoma
      mansoni. Both epitopes contain fucose: mAb 128C3/3, as we have shown previously,
      recognizes fucose in a novel, possibly internal linkage (Levery et al. 1992)
      while mAb 504B1, as we show here, bound to the Le(x) epitope, which contains
      fucose alpha 1-->3 linked to N-acetyl-glucosamine. The tissue expression of these
      epitopes was strikingly different and both elicit an immune response in infected
      hosts. The mAb 128C3/3-defined epitope was exposed on the surface of all larval
      stages but not on adult worms; however, it was found in the excretory system of
      adult worms of both sexes. In contrast, surface expression of the Le(x) epitope
      was initiated after the transformation of cercariae to schistosomula and was
      maintained throughout the adult life in both sexes.

PMID- 7516536
TI  - The team approach to pediatric asthma education.
AB  - An interdisciplinary pediatric pulmonary team of nurses, pharmacists, and social
      workers developed an asthma education program for presentation to children with
      asthma, ages 7-11, in a camp setting. Sound educational principles provide the
      foundation for this program, which includes a variety of teaching methods
      including puppet shows, games, crafts, and song. Informal evaluation methods of
      observation and feedback indicated that children's knowledge of asthma and asthma
      management increased.

PMID- 7516537
TI  - Nurse education. Sound sense.

PMID- 7516538
TI  - Fragmented research: costly to the patient, the investigator, and society.

PMID- 7516540
TI  - Study of late potentials and ventricular arrhythmias in hypertensive patients
      with normal electrocardiograms.
AB  - INTRODUCTION: Although an increase in the occurrence of ventricular arrhythmias
      has been observed in hypertensive patients, some basic questions remain
      unresolved regarding the prevalence and the pathophysiology of these arrhythmias.
      The basic aims of this study were as follows: (1) to examine the incidence and
      severity of ventricular arrhythmias in a substantial number of hypertensive
      patients without electrocardiographic indications of hypertrophy; and (2) to
      examine the correlation between late potentials, hypertrophy, and ventricular
      arrhythmias in these patients. MATERIALS AND METHODS: We studied 78 consecutive
      patients (31 men, 47 women), aged 60.5 +/- 7.8 years, with a history of
      hypertension but a normal electrocardiogram. All patients had an
      echocardiographic study, 24-hour ambulatory monitoring, exercise test, and signal
      averaged electrocardiogram. The latter was analyzed using a 40- to 250-Hz filter
      and with a noise level < or = 0.3 microV. RESULTS: Of the 78 patients studied, 21
      (26.9%) had severe ventricular arrhythmias, while 57 (73.1%) had either no
      ventricular ectopics or sporadic isolated ventricular extrasystoles. Left
      ventricular hypertrophy, defined by echocardiography, was found in 58 patients
      (74.3%), of which 16 (27.58%) had severe ventricular arrhythmias. Five (25%) of
      the 20 patients without hypertrophy also had severe ventricular arrhythmias (P =
      NS). Ventricular late potentials were recorded in 19 (24.5%) of the 78 patients.
      Of these, 11 (57.89%) had severe arrhythmias, while of the 59 patients without
      late potentials 10 (16.94%) had severe ventricular ectopic activity. CONCLUSIONS:
      In hypertensive patients without electrocardiographic signs of hypertrophy, the
      higher prevalence of ventricular arrhythmias does not appear to be related to
      left ventricular hypertrophy but is correlated with the existence of ventricular
      late potentials.

PMID- 7516541
TI  - Effect of pacing site on the atrial electrogram at target sites for slow pathway
      ablation in patients with atrioventricular nodal reentrant tachycardia.
AB  - Atrial electrograms recorded from target sites during radiofrequency catheter
      ablation of the slow atrioventricular (AV) nodal pathway are often fractionated
      and may be associated with a late, high frequency component (the slow pathway
      potential). The purpose of the current study was to assess the effects of slow
      pathway ablation on the morphology of the atrial electrogram and to determine
      whether target site electrograms display direction dependent changes in
      morphology during atrial pacing maneuvers. Twenty-six patients with typical AV
      nodal reentry had electrograms recorded from target sites before and after
      successful ablation of the slow AV nodal pathway and during pacing from the high
      right atrium and distal coronary sinus at cycle lengths of 500 and 300 msec.
      There was no significant change in the duration or degree of fractionation of the
      atrial electrogram as the result of slow pathway ablation. In contrast, the
      duration and degree of fractionation were less when pacing from the coronary
      sinus compared with sinus rhythms or right atrial pacing. Pacing rate did not
      affect electrogram morphology. These data suggest that the morphology of the slow
      pathway target site electrogram is dependent on the direction of atrial
      activation and that the "slow pathway potential" does not represent activation of
      an anatomically discrete pathway.

PMID- 7516539
TI  - Low dose disopyramide often fails to prevent neurogenic syncope during head-up
      tilt testing.
AB  - Low dose disopyramide has been used to prevent neurally-mediated syncope during
      head-up tilt testing but a correlation between blood levels and efficacy has not
      been described. We measured disopyramide levels in 15 patients with recurrent
      syncope and positive 70 degrees head-up tilt tests who underwent one or more
      repeat tests on the drug. There were 9 males and 6 females, age range 15-78
      years. Fourteen of the 15 patients had structurally normal hearts. The daily
      disopyramide dose was 645 +/- 165 mg (mean +/- SD). Patients developed syncope
      during 9 tests and had no syncope during 12 tests. The mean disopyramide level in
      patients with positive tests was significantly lower than the level in patients
      with negative tests (2.4 +/- 0.15 mu/mL vs 3.2 +/- 0.22 mu/mL, P = 0.018). Six
      patients were tested twice on different disopyramide doses. Five of these six
      patients had syncope during head-up tilt testing on the lower dose and negative
      tests on the higher dose (disopyramide levels 2.2 +/- 0.17 mu/mL vs 3.2 +/- 0.17
      mu/mL, P = 0.004). Thus, disopyramide is effective in preventing neurogenic
      syncope during head-up tilt testing, but higher blood levels are often necessary
      for efficacy. In a given patient, failure to respond to low dose disopyramide
      does not preclude success on higher doses.

PMID- 7516542
TI  - Radiofrequency catheter ablation of accessory pathways during entrainment of AV
      reentrant tachycardia.
AB  - Radiofrequency ablation of accessory pathways must sometimes be done during
      orthodromic atrioventricular reentrant tachycardia when manifest anterograde
      accessory pathway conduction is absent or retrograde fusion obscures accessory
      pathway location during ventricular pacing. Unfortunately, abrupt heart rate
      slowing upon radiofrequency induced termination of atrioventricular reentrant
      tachycardia often causes catheter dislodgment. We report our experience in
      circumventing this problem during radiofrequency ablation by using entrainment of
      atrioventricular reentrant tachycardia. The latter maintains retrograde
      activation pattern over the accessory pathway while preventing abrupt ventricular
      rate change. Eight patients (4 men and 4 women, mean age 37.3 +/- 17.9) with
      eleven left-sided accessory pathways were included. Ablation during entrainment
      was used as the first approach in three patients with concealed accessory
      pathways and one patient with a bidirectional accessory pathway. In another four
      patients, ablation during entrainment was used after technical difficulties in
      ablating during tachycardia. Only 1-3 radiofrequency applications were required
      to eliminate the accessory pathway using the entrainment technique. The catheter
      remained stable when accessory pathway conduction was interrupted by
      radiofrequency current. In conclusion, entrainment of atrioventricular reentrant
      tachycardia during radiofrequency application is useful for maintaining catheter
      position for accessory pathway ablation during atrioventricular reentrant
      tachycardia.

PMID- 7516543
TI  - Automated precision current delivery: an alternative method for cardiac
      defibrillation.
AB  - Substantial evidence suggests that the current associated with the discharge is a
      more precise predictor of defibrillation success than is the total energy of the
      discharge. However, virtually all commercially available defibrillators are
      calibrated in terms of energy. This article describes an alternative type of
      experimental defibrillator, which provides a precisely controlled current
      throughout the discharge waveform, independent of the load presented to the
      discharge electrodes (or "paddles"). The discharge current waveform is designed
      to have the classical critically damped sinusoid waveform, identical to that of
      the traditional energy-based defibrillator when it is properly matched with its
      ideal load (the heart/thorax combination). The techniques used to obtain a
      controlled current discharge are discussed in addition to special operational
      features.

PMID- 7516545
TI  - Differentiation of beats of ventricular and sinus origin using a self-training
      neural network.
AB  - Despite advances in the computerized detection of arrhythmias, arrhythmia
      recognition by morphological waveform analysis still poses a difficult problem.
      Artificial neural networks, computer algorithms that are self-trained by an
      analog of biological synaptic modification to perform pattern recognition, hold
      great promise for the differentiation of various cardiac rhythms. The goal of
      this study was to differentiate beats of sinus and ventricular origin on a global
      basis and on a patient-specific basis by the use of artificial neural network
      analysis. Neural networks were trained to recognize digitized intracardiac
      electrograms (9 patients) and surface electrocardiograms (11 patients) obtained
      during sinus rhythm and ventricular tachycardia. After training, sinus rhythm or
      ventricular tachycardia beats were input into the neural network, and classified
      as to their origin. By the use of modified receiver operating characteristic
      curve plots, it was possible to differentiate with high sensitivity and
      specificity between beats of sinus origin and ventricular origin in all patients.
      The addition of high amounts of noise to the beats did not markedly degrade the
      performance of the surface ECG neural networks, and still allowed high
      sensitivity in differentiating beats of sinus origin from beats of ventricular
      origin, especially when noise was added to the training set. Neural networks
      provided sensitive and specific detection of cardiac electrical activity during
      sinus rhythm and ventricular tachycardia, and may play an important role in
      allowing development of improved arrhythmia recognition and management systems.

PMID- 7516544
TI  - Efficacy and safety of ventricular rate responsive pacing in children with
      complete atrioventricular block.
AB  - Single chamber rate responsive pacing offers many potential advantages over the
      more complex dual chamber atrial tracking pacing mode in children, and the
      preservation of atrioventricular synchrony could be unnecessary in selected
      groups of pediatric patients. Twenty-two pediatric patients (age range 9 months
      to 12 years; mean 6.5 years) had implantation of ventricular rate responsive
      (VVIR) pacemakers over a 2-year period. All patients had chronic third-degree
      atrioventricular block, and a normal ventricular function at rest. During the
      follow-up each patient underwent a 24-hour Holter monitoring, and ten performed a
      graded treadmill test in both ventricular fixed rate (VVI) and rate responsive
      (VVIR) pacing mode. Paced ventricular rates were found to be normal for age in
      all 22 patients; maximum rate did not reach the higher programmed rate during
      daily activities in any patient. Comparing the mean paced ventricular rate to the
      mean rates of blocked P waves, six patients showed a difference of more than 20
      beats/min, which induced the pacemaker parameters to be reprogrammed. In all
      patients a significant correlation was found between variations of paced
      ventricular rate and variations of spontaneous blocked atrial rhythm (P < 0.05);
      this correlation persisted in the subsequent Holter controls in the ten patients
      with longer follow-up. Exercise tolerance resulted normal in the ten patients who
      performed a treadmill test either in VVIR or VVI mode, with increased maximal
      heart rates and maximal systolic blood pressure in VVIR mode (P < 0.0013). Rate
      responsive ventricular pacemakers seem to adequately respond to the physiological
      needs of daily life of this selected group of children requiring permanent
      pacing.

PMID- 7516546
TI  - Plasma ANP and cyclic GMP levels versus left ventricular performance at different
      AV delays in AV sequential pacing.
AB  - Eleven resting patients with an implanted DDD pacemaker were studied. After 30
      minutes of AV sequential pacing at a rate of 80 beats/min with three consecutive
      atrioventricular delays (AVDs; 100, 150, and 200 msec) peripheral venous blood
      was drawn for further analyses by specific radioimmunoassays of atrial
      natriuretic peptide (ANP) and the ANP second messenger, cyclic guanosine
      monophosphate (cGMP). Relative changes in left ventricular (LV) stroke volume
      following alterations of AVD were assessed by means of pulsed-Doppler
      echocardiography through measurement of LV outflow time-velocity integrals (TVI).
      The optimal AVD (oAVD) was defined in individual patients as that which was
      associated with the greatest TVI and with improvement over both other AVDs of
      more than 4%. The oAVD was found in nine patients. For these nine patients no
      significant differences in either plasma ANP or cGMP between various AVDs were
      observed. However, we found such differences with respect to values measured at
      oAVD; both ANP and cGMP levels were lowest at oAVD. Pooling together the data
      obtained in 11 patients at three AVDs, a positive correlation between ANP and
      cGMP levels was found (r = 0.7, P < 0.0001, n = 33). Moreover, changes of plasma
      ANP and cGMP induced by every AVD increment of 50 msec were also correlated (r =
      0.6, P < 0.01, n = 22). It is concluded that in AV sequential pacing at rest
      plasma ANP reaches minimal levels at the AVD, which provides the best LV
      performance. Although levels of cGMP changed in parallel with those of ANP, low
      relative values of cGMP differences may limit the usefulness of cGMP assays in
      optimization of the AVD.

PMID- 7516547
TI  - The clinical significance of nonsustained ventricular tachycardia: current
      perspectives.

PMID- 7516548
TI  - Inappropriate discharge by an implantable cardioverter defibrillator: recognition
      of myopotential sensing using telemetered intracardiac electrograms.
AB  - Inappropriate therapy from implantable anti-tachyarrhythmia devices is a common
      problem with a variety of etiologies. The verification of arrhythmias or other
      sensed events that precipitate defibrillating shocks is difficult with first- and
      second-generation devices due to the absence of sufficient data storage and the
      inability to examine stored and real-time intracardiac electrograms. In addition,
      the absence of premonitory symptoms is an unreliable marker for the
      appropriateness of defibrillator shocks. The incorporation of improved data
      storage and the ability to inspect intracardiac electrograms in newer devices
      have greatly increased the ability to diagnose abnormal device behavior as shown
      in the following case report. Inappropriate implantable cardioverter
      defibrillator discharge due to myopotential sensing is described. The diagnosis
      was facilitated by telemetered intracardiac electrograms.

PMID- 7516550
TI  - Permanent ventricular pacing via the great cardiac vein.
AB  - Two cases of left ventricular pacing via the great cardiac vein are presented. A
      64-year-old female with a mechanical prosthetic tricuspid valve and slow atrial
      fibrillation had a failed attempt at pacing from the middle cardiac vein. In a 58
      year-old male with hypertrophic obstructive cardiomyopathy and bradycardia
      tachycardia syndrome, transvenous permanent pacing could not be achieved via the
      right ventricle or middle cardiac vein. In both cases, successful pacing via the
      great cardiac vein was achieved but with an elevated stimulation threshold. These
      cases illustrate an alternate transvenous route when difficulties occur using
      standard ventricular pacing sites.

PMID- 7516549
TI  - Histopathological changes following laser ablation of a left-sided accessory
      pathway in a human.
AB  - Laser ablation was performed intraoperatively in a patient with coronary artery
      disease and Wolff-Parkinson-White syndrome. Histopathological evaluation of the
      laser ablation site revealed a transverse laser incision in the left atrial
      septum and mitral valve annulus. There was hemorrhage in the atrioventricular
      (AV) groove with interruption of a posterolateral AV connection. The laser lesion
      was confined largely to the atrial aspect of the AV annulus. We conclude that
      laser catheter ablation of accessory pathways is feasible in humans.

PMID- 7516551
TI  - A 42-year-old female patient received endocardial pacing.

PMID- 7516552
TI  - A serious case of radiofrequency EMI, when an ICD wearer manipulated a remote
      control of a toy car.

PMID- 7516553
TI  - STIMAREC report.

PMID- 7516554
TI  - The Bilitch report.

PMID- 7516555
TI  - Performance of implantable cardiac rhythm management devices.

PMID- 7516556
TI  - [Treatment of drug induced agranulocytosis with granulocyte-macrophage colony
      stimulating factor (G-CSF)].
AB  - G-CSF was applied in three patients with acute, iatrogenic, immunological
      agranulocytosis (after ticlopidine, thimazol and aminoglutethimide) complicated
      by severe infections. Before this treatment was started no improvement had been
      achieved despite the administration of antibiotics, and corticosteroids for 4 to
      9 days. Two patients had anaemia and one--thrombocytopenia probably due to the
      damage to the earlier, common progenitor cells. In bone marrow smears a
      plasmocytic reaction reaching 11-13% of total cell counts was observed. After G
      CSF all patients showed a prompt amelioration of clinical symptoms, and the
      leucocyte count raised in several days up to 11.0-73.0 x 10(3)/microliters.
      Simultaneously young cellular forms of granulocyte lineage appeared in peripheral
      blood.

PMID- 7516557
TI  - Extraction of neuropeptides from joint tissue for quantitation by
      radioimmunoassay. A study in the rat.
AB  - The feasibility of extracting neuropeptides from rat knee joints for quantitation
      by radioimmunoassay was tested. The investigation, based on 25 adult Lewis rats,
      focused on substance P, calcitonin gene-related peptide, neuropeptide Y, and
      vasoactive intestinal polypeptide. The relative recovery of the peptides in
      different extraction media was assessed Both knee joints including the
      articulating epiphysis were dissected and cut into small pieces. The series was
      divided into five subgroups, 10 joints in each, for extraction in five different
      media: 1) 1 M acetic acid in 4% EDTA, 2) 2 M acetic acid in 4% EDTA, 3) neutral
      water in 4% EDTA, 4) 2 M acetic acid in 4% EDTA and 95% alcohol, and 5) 2 M
      acetic acid without EDTA. Measureable concentrations of the four neuropeptides
      were reproducibly assessed by RIA. Although all extraction media provided
      measurable concentrations, 2 M acetic acid in 4% EDTA was found to give the
      highest overall yield of the four neuropeptides analyzed. Reverse-phase HPLC
      confirmed that the immunoreactivities assessed by RIA corresponded to the four
      neuropeptides of interest. Experimental and clinical evidence suggest a
      neurogenic involvement in the pathophysiology of inflammatory joint disease,
      e.g., rheumatoid arthritis. The extraction procedure described offers a means of
      determining neuropeptide concentrations in joint tissue under normal and
      pathologic conditions by RIA.

PMID- 7516558
TI  - Effect of capsaicin on distribution of binding sites for tachykinins and
      calcitonin gene-related peptide in rat urinary bladder: a quantitative
      autoradiographic study.
AB  - The autoradiographic localization of binding sites for [125I]BH
      [Sar9,Met(O2)11]SP, [125I]NKA, and [125I]CGRP was investigated in adjacent
      sections of urinary bladder body, from adult rats pretreated 14 days before with
      capsaicin or vehicle. Location of silver grains was assessed both qualitatively
      and quantitatively using computerized densitometry. Dense labeling of smooth
      muscle was seen with both [125I]BH-[Sar9,Met(O2)11]SP ([125I]BHSar-SP) and
      [125I]NKA; in addition, [125I]BHSar-SP labeled submucosal blood vessels. For
      these radioligands, no differences were apparent between sections from capsaicin-
      and vehicle-pretreated rats. Specific binding of [125I]CGRP was observed over the
      epithelium and weakly over submucosal arterioles, but not over smooth muscle. The
      density of [125I]CGRP binding sites on the epithelium, but not blood vessels, was
      increased (p < 0.05) by 22% after chronic capsaicin pretreatment, suggesting
      receptor upregulation. This study demonstrates that although all three peptides
      are colocalized in primary afferent sensory fibers in rat urinary bladder, the
      receptors for these neuropeptides are located on different cell types and may be
      subject to different neural influences.

PMID- 7516559
TI  - Blockade of sensitization to the toxic effects of cocaine in mice by nitric oxide
      synthase inhibitors.
AB  - Repeated administration of cocaine to animals results in sensitization to several
      reactions to the drug, including seizures and mortality. These consequences are
      thought to be related to the pathology that develops in humans abusing cocaine.
      Previous studies implied the involvement of the N-methyl-D-aspartate (NMDA) type
      of glutamate receptors in cocaine-induced toxicity, and recent studies documented
      a role for nitric oxide in NMDA-receptor mediated neurotoxicity. The present
      study was undertaken to determine whether nitric oxide synthase inhibitors block
      the development of sensitization to the toxic effects of cocaine in mice.
      Repeated administration of cocaine (45 mg/kg/day; intraperitoneally) to Swiss
      Webster mice, for 7 days, resulted in a progressive increase in the duration of
      the convulsive response to cocaine, an increase in the number of animals that had
      seizures, and augmentation in lethality rate. Pretreatment with NG-nitro-L
      arginine methyl ester (L-NAME; 100 mg/kg/day; intraperitoneally) or NG-nitro-L
      arginine (NO-Arg; 25 mg/kg/day; intraperitoneally) completely abolished the
      sensitization to the convulsive and lethal responses to cocaine. Receptor binding
      assays indicated first, that pretreatment with L-NAME apparently diminished
      cocaine-induced upregulation of cortical NMDA receptors, and second, that the
      effects of the nitric oxide synthase inhibitors tested are not mediated via a
      direct interaction of the drugs with the phencyclidine/NMDA receptor complex.
      Taken together, the present study suggests an important role for nitric oxide in
      the development of sensitization to the toxic effects of cocaine, and further
      supports the relationship between NMDA-receptor mediated neurotoxicity and nitric
      oxide.

PMID- 7516560
TI  - Identification of 72-kilodalton type IV collagenase at sites of trophoblastic
      invasion of macaque spiral arteries.
AB  - The walls of uterine spiral arteries are invaded by extravillous trophoblast
      cells and are thereby converted to the uteroplacental arteries of pregnancy. The
      mechanisms by which this invasion occurs are not understood, but the
      extracellular matrices that are breached suggest participation by specific
      proteinases. In this report we describe the immunohistochemical localization of
      72-kd type IV collagenase (gelatinase A or MMP-2) among intra-arterial
      trophoblast cells and endometrial cells during development of macaque
      uteroplacental arteries. Cytokeratin-positive trophoblast cells were identified
      within arteries at each stage studied (between days 22-128 of gestation). Many of
      these cells, whether located in the arterial lumen or within the vessel wall,
      were immunoreactive for the proteinase. Early in the invasive process these
      trophoblast cells were associated with discontinuities of the endothelial
      basement membrane and later became interspersed with smooth muscle cells of the
      tunica media. While trophoblast cells comprised the entire thickness of the
      arterial wall in many locations, typically only a subset of these cells expressed
      the proteinase. Many endometrial stromal cells were also immunoreactive for the
      proteinase, as were some arterial endothelial and smooth muscle cells. It is
      concluded that this, and probably other, proteinases are active throughout
      gestation in the restructuring of uterine spiral arteries and other endometrial
      tissues as necessary to accommodate the development of the fetus.

PMID- 7516561
TI  - Methods in pathology. Optimization of proliferating cell nuclear antigen
      immunohistochemical staining by microwave heating in zinc sulfate solution.
AB  - Immunohistochemical staining of routinely processed formalin-fixed, paraffin
      embedded archival tissue sections with proliferating cell nuclear antigen (PCNA)
      monoclonal antibody has facilitated the understanding of the regulation of cell
      proliferation. However, false-negative staining due to masking or poor
      preservation of antigen epitopes by fixatives or other unknown conditions has
      been a major problem in PCNA immunohistochemical studies. Microwave heating (MWH)
      has been used to retrieve antigen in archival tissue. However, optimal staining
      conditions have not yet been defined. We therefore investigated the effect of MWH
      with or without a metal solution (zinc sulfate) on routinely processed paraffin
      embedded tissue to determine the optimal conditions for retrieval of PCNA. The
      results were compared with routine immunohistochemical staining. We found that
      MWH in 1% zinc sulfate solution successfully retrieved PCNA; the optimal MWH time
      was 7.5 mins. In contrast, when MWH was performed in water, the specific
      intensity of PCNA expression was not increased because MWH not only enhanced the
      intensity of the antigen staining but also increased the background staining. In
      summary, MWH technique in zinc-sulfate solution allowed successful PCNA retrieval
      from formalin-fixed archival tissue and thus facilitated accurate
      immunohistochemical evaluation of cell proliferative activity in cancers.

PMID- 7516562
TI  - [A proposal for the use of tridimensional reconstruction in oncology to better
      assess tumor stage and response to therapy].
AB  - Besides radiation therapy, diagnostic imaging has always been considered the main
      medical application of three-dimensional (3D) reconstruction. On the contrary,
      our study focused mainly on the use of 3D reconstruction for both spatial
      characterization and morphometric evaluation of the reconstructed objects. We
      aimed at assisting physicians to solve clinical and therapeutic problems. In
      particular, in oncology, 3D reconstruction may allow the objective and accurate
      quantification of the volume of neoplastic lesions. Therefore, we decided to
      focus our attention on the spatial characterization and morphometric assessment
      of the examined neoplastic masses. Volumetric measurements based on 3D
      reconstruction may be of great value to assess volume changes after irradiation
      and/or chemotherapy of neoplastic lesions. This might also allow to compare, on
      the basis of such changes, the role of different treatment protocols on similar
      neoplastic lesions and, possibly, to lead to a new TNM staging system no longer
      based on 2D measurements but on volumes. To meet these clinical requirements, we
      developed a software system for accurate volume measurements. We believed 3D
      reconstruction to be suited to this purpose and therefore we implemented a
      software incorporating 3D reconstruction capabilities of abnormal anatomical
      structures from 2D images, the rotation of the volume of interest for better
      assessment of spatial relationships, and finally morphometric evaluation, for
      accurate volume measurements. Instead of calculating the volume of a neoplastic
      lesion by means of a 3D reconstruction algorithm considering voxels as
      indivisible (voxel-based approach), we implemented a surface rendering algorithm
      using a cell-based approach, because it allowed voxels to be represented as small
      volume units, which could be further divided by means of linear interpolation.
      Thus, great flexibility was possible in the determination of surfaces, together
      with a good approximation of the volume of the neoplastic lesions. To assess the
      reliability of the developed software system, we used a real phantom. Its known
      actual volume was compared with the one measured by our system and the
      difference, expressed as a percentage of the actual volume itself, was compared
      with the one obtained by using reconstruction algorithms with a voxel-based
      approach (1.4% vs 4.4%). The error produced by the latter is three times greater
      than the one produced by our algorithm. This is a major result for the physician:
      better approximation of the actual volume of a neoplastic lesion means better
      evaluation of the number of neoplastic cells in the lesion. This may be useful
      for the clinical management of the patient. In the paper, the first clinical
      applications of our algorithm are reported.

PMID- 7516563
TI  - Effects of amino acid sequence changes on antibody-antigen interactions.

PMID- 7516566
TI  - Protein epitopes: functional vs. structural definitions.

PMID- 7516565
TI  - Do antiidiotypic antibodies mimic antigen?

PMID- 7516564
TI  - Structural implications of somatic mutations during the immune response to 2
      phenyloxazolone.

PMID- 7516567
TI  - [Isolated inflammatory syndrome: think of benign tumors of the liver].
AB  - The authors report seven cases of benign tumors of the liver revealed by elevated
      acute phase reactants. They show that these elevated acute phase reactants are
      not linked with a particular histological diagnosis, the presence of tumor
      necrosis and that they disappear with the chirurgical cure of the tumor.

PMID- 7516568
TI  - [Systemic mastocytosis: incidence and risks of vasomotor seizures].
AB  - We report on 9 cases of systemic mastocytosis which underline the frequency and
      the potential severity of this disease. All patients had intercritical signs
      (usually urticaria). Seven patients had also typical crises with flush and
      vascular collapses are observed together, doctors should measure histamine blood
      level and perform correct biopsy.

PMID- 7516570
TI  - [Fatal peripheral neuropathy with predominant motor involvement associated with
      anti-MAG IgM monoclonal gammapathy].
AB  - A 75 year old woman died of predominantly motor peripheral neuropathy with
      amyotrophy and fasciculations progressing to tetraplegia and death within 19
      months. There was a mild distal sensory loss. At electrophysiology, the pattern
      was initially demyelinating and later became axonal. Nerve biopsy disclosed
      severe myelinated and unmyelinated fiber loss with wallerian degeneration. The
      remaining fibers had demyelination widening of the external myelin lamellae and
      intense hypermyelination. Serum contained an anti-MAG monoclonal IgM reacting
      with SGPG. Two siblings without monoclonal gammopathy had died of definite
      amyotrophic lateral sclerosis. This family association is discussed.

PMID- 7516571
TI  - Amino acids in the peptide-binding groove influence an antibody-defined, disease
      associated HLA-DR epitope.
AB  - A shared amino-acid sequence on the alpha helix of certain DR beta 1 chains is
      predicted to generate a 'shared epitope' that is implicated in susceptibility to
      the development of rheumatoid arthritis (RA). Different relative risks (RR) for
      disease susceptibility and severity conferred by these DR beta 1 chains suggest
      that their 'shared epitopes' are not equivalent. A set of monoclonal antibodies
      (MoAb) that map to the critical region, and for which optimal binding depends on
      DR context and cell lineage, was used to test this idea. Mapping experiments
      using mutated DR beta 1* molecules showed that the antibody-binding epitopes are
      overlapping; residue 70Q is pivotal for each, but neighbouring residues on the
      alpha helix and on the floor of the groove are also involved. Importantly, these
      epitopes are profoundly modified by peptide loading of DR beta 1*0401 molecules.
      These data suggest that 'shared epitopes' on DR molecules that are associated
      with RA are influenced by their context; such structural modifications may be the
      basis for the varying susceptibilities conferred by these DR molecules for the
      development of RA.

PMID- 7516569
TI  - [Quality of life in geriatric surgery].

PMID- 7516572
TI  - Basic amino acids predominate in the sequential autoantigenic determinants of the
      small nuclear 70K ribonucleoprotein.
AB  - Autoantibodies binding the 70K nRNP polypeptide are commonly found in the serum
      of patients with systemic lupus erythematosus. IgG antibodies binding overlapping
      octapeptides of 70K nRNP have been evaluated in 10 patients with anti-nRNP
      precipitins, seven patients with other autoimmune serology, and four normal human
      sera. Neither normal controls nor patients without an anti-nRNP precipitin
      significantly bind any of the 70K nRNP octapeptides. Sera containing an anti-nRNP
      precipitin strongly bind various combinations of eleven different regions of the
      70K nRNP protein. One antigenic region is consistently the most reactive in nine
      of ten nRNP precipitin positive sera tested. This sequence, KDKDRDRKRRSSRSR, is
      highly charged and has a similar pattern of alternating basic amino acids also
      present in seven of the other purported humoral autoimmune epitopes of the 70K
      nRNP polypeptide. The closely related DRKR and ERKR are important components of
      two of these epitopes. All regions of the 70K peptide bound by human anti-nRNP
      precipitin positive sera are very rich in the basic amino acids, especially
      lysine (chi-square = 23.03, odds ratio = 13.3, P < 0.000001).

PMID- 7516573
TI  - Peptide specificity of anti-myelin basic protein antibodies in patients with
      acute optic neuritis and the HLA system.
AB  - Multiple sclerosis (MS) may be an autoimmune disease, partially caused by
      autoreactivity to myelin basic protein (MBP) and other central nervous system
      proteins. Acute optic neuritis (ON) is a frequent first symptom of MS. The role
      of the HLA system in anti-MBP antibody production in ON was investigated
      employing a restriction fragment length polymorphism system for genomic HLA-DQ
      and -DR typing and an immunospot assay for the detection of individual cells
      secreting antibodies to three different synthetic MBP peptides. Thirty-two out of
      40 patients (80%) with ON had cells in cerebrospinal fluid secreting anti-MBP
      peptide antibodies while this occurred in 10/19 patients with other neurological
      diseases (53%; mainly in patients with inflammatory diseases in the central
      nervous system). This difference was statistically significant (P = 0.03). None
      of the three examined peptides were immunodominant in any patient group. It was
      found, however, that presence of HLA DR15, which is associated with MS, may be
      associated further with predominant production of antibodies to the MBP amino
      acids 63-88 in patients with ON (P = 0.002, corrected for multiple comparisons).

PMID- 7516574
TI  - Individuals from different populations identify multiple and diverse T-cell
      determinants on mycobacterial HSP70.
AB  - The 70 kDa heat-shock protein (HSP) of Mycobacterium leprae stimulates both
      cellular and antibody responses in leprosy patients and subclinically infected
      individuals despite partial homology with host HSP70. Furthermore, mycobacterial
      HSP70 can act as a carrier protein in unprimed mice, suggesting the presence of
      widely shared T-cell determinants on this protein. In order to elucidate the
      frequency and genetic restriction of these T-cell epitopes, we have undertaken a
      systematic analysis of the proliferative responses to 20mer peptides encompassing
      the whole protein in different populations. Caucasian BCG vaccinees who responded
      to recombinant M. leprae HSP70 identified multiple scattered T-cell determinants,
      four of which were recognized by 60% of subjects in association with a variety of
      HLA-DR haplotypes. When a group of Nepali leprosy and tuberculosis patients were
      tested, significant differences in the pattern of peptide recognition were
      observed. The dominant peptides recognized by Caucasian subjects were
      infrequently reactive and other peptides were stimulatory, again in association
      with a variety of HLA-DR phenotypes. The C-terminal 70 residues of the M. leprae
      HSP70 are specific to M. leprae and sera from lepromatous leprosy patients bind
      to this region. However, few T-cell determinants were identified in these
      residues, indicating that this region is unhelpful as a diagnostic tool for
      detecting M. leprae-specific T-cell responses. When compared with the equivalent
      regions of the human HSP70, the commonly recognized peptides showed significant
      differences in amino-acid sequence. When taken in conjunction with the failure of
      human HSP70 to stimulate M. leprae HSP70-reactive T-cell clones (E. Adams et al.,
      unpublished observations), this finding indicates that the human T-cell response
      to this protein is largely directed at mycobacterial-specific determinants. The
      presence of multiple T-cell epitopes on M. leprae HSP70 with varied patterns of
      HLA-DR association suggests that the whole protein is required for stimulating
      effective T-cell responses in genetically diverse populations.

PMID- 7516575
TI  - Precision of a patient-weighted symptom score in prostatism. The DAN-PSS-1
      questionnaire.
AB  - The Danish Prostatic Symptom Score (DAN-PSS-1) comprises 12 questions related to
      voiding problems in benign prostatic hyperplasia. The patient himself scores each
      symptom as regards severity (symptom score) and impact on daily life (bother
      score). The precision of this patient-weighted (postal) questionnaire was
      investigated in terms of repeat frequencies of replies from 197 randomly selected
      men on two sequential occasions. The questionnaire was well understood by the
      patients. The median frequency of repeat in answers to the questions was 83.5%
      (range 0-99.7%). This frequency depended on the nature of the question and the
      severity or bother of the symptom. Repeatability as regards bother rose markedly
      when the bother score was made dependent of the symptom score, suggesting a
      relationship between the two. As with other questionnaires, the precision of
      those dealing with prostatism should be established before clinical use. The
      observed relationship between symptom score and bother score may be of diagnostic
      value.

PMID- 7516577
TI  - Transurethral microwave thermotherapy for uncomplicated benign prostatic
      hyperplasia. A prospective study with emphasis on symptomatic improvement and
      complications.
AB  - A single session of transurethral microwave thermotherapy (TUMT) was used in 115
      patients with symptomatic uncomplicated benign prostatic hyperplasia (BPH).
      Subjective symptoms and urodynamic parameters were assessed before treatment, at
      6 weeks, 3, 6 and 12 months after treatment and complications recorded. There was
      significant improvement in obstructive, irritative and total symptom scores at
      all time intervals. The maximum and corrected flow rate improved significantly at
      all time intervals as well as the decrease in residual urine. Complications
      occurred in 45.2% patients with no mortality. The most frequent complications
      were urinary tract infection (32.1%) and urinary retention (28.6%). Two patients
      experienced retrograde ejaculation. No patient was hospitalized due to
      complication. Four (3.5%) patients required transurethral resection of the
      prostate during the follow-up period due to persistent symptoms; 96.5% have
      remained satisfied. In conclusion, TUMT is a promising treatment option in
      selected patients with BPH, is well tolerated and complications are easy to
      treat. Its main advantage is the fact that it can be administered on an
      outpatient basis, thus reducing patient inconvenience and costs.

PMID- 7516576
TI  - 29-week doxazosin treatment in patients with symptomatic benign prostatic
      hyperplasia. A double-blind placebo-controlled study.
AB  - In a placebo-controlled study, the safety and efficacy of the selective alpha 1
      adrenoceptor-blocking agent doxazosin 4 mg once daily in the symptomatic
      treatment of benign prostatic hyperplasia (BPH) were evaluated. One hundred
      patients were primarily included in a 9-weeks study, and after this 75 patients
      accepted to continue in the present 20 weeks extension. Of the patients in the
      doxazosin-group (DG) 61% reported overall improvement against 53% in the placebo
      group (PG)--(p = 0.56). In the DG, 49% of obstructive symptoms were improved
      compared to 27% in the PG (p < 0.01), and a reduction of 60% of irritative
      symptoms was found in the DG against 36% in the PG (p < 0.01). Daytime frequency
      was reduced by median 1.5 in the DG and remained unchanged in the PG (p < 0.01).
      Nocturia was reduced by median 1 and 0.5 respectively (p = 0.06). Maximum urinary
      flow rate (MFR) was improved by median 1.5 ml/s in the DG, while it deteriorated
      by median 0.5 ml/s in the PG (p < 0.05), Considering postvoid residual urine
      volume, cystometry variables (first sensation and bladder capacity), changes in
      sexual function and adverse events there was no difference between the two
      groups. In conclusion, doxazosin 4 mg once daily in long-term treatment of
      patients with BPH reduces both obstructive and irritative symptoms, daytime
      voiding frequency and although only slightly, significantly augments MFR without
      interference with sexual function and without other serious adverse effects.

PMID- 7516578
TI  - The use of ethanol-tagged mannitol in transurethral resection of the prostate
      does not alter the bleeding time in patients who absorb irrigation fluid.
AB  - To increase patient safety ethanol tagging of irrigation fluid is practised at
      several hospitals in Sweden to detect absorption of irrigation fluid during
      transurethral prostatic resection. Using this method it is found that almost half
      of the patients undergoing transurethral prostatic resections absorb irrigation
      fluid to some extent. Patients absorbing irrigation fluid bleed more than others.
      The phenomenon has been blamed on the open veins and sinusoides. Further, these
      patients are older, have larger prostates and longer operating times. To exclude
      an effect of ethanol-tagged irrigation fluid on the skin bleeding time this was
      measured before and after the operation in 57 patients. In 18 (32%) 160-1760 ml
      of irrigation fluid was absorbed, and in 9 patients over 480 ml. No difference in
      skin bleeding time emerged between absorbers and non-absorbers, and absorbers
      showed no differences in bleeding time between preoperative and postoperative
      values. There was a slight but insignificant decrease in the skin bleeding time
      after the operation in both absorbers and non-absorbers.

PMID- 7516579
TI  - Antigenic variation in African trypanosomes.

PMID- 7516580
TI  - Structures of ternary complexes of rat DNA polymerase beta, a DNA template
      primer, and ddCTP.
AB  - Two ternary complexes of rat DNA polymerase beta (pol beta), a DNA template
      primer, and dideoxycytidine triphosphate (ddCTP) have been determined at 2.9 A
      and 3.6 A resolution, respectively. ddCTP is the triphosphate of dideoxycytidine
      (ddC), a nucleoside analog that targets the reverse transcriptase of human
      immunodeficiency virus (HIV) and is at present used to treat AIDS. Although
      crystals of the two complexes belong to different space groups, the structures
      are similar, suggesting that the polymerase-DNA-ddCTP interactions are not
      affected by crystal packing forces. In the pol beta active site, the attacking 3'
      OH of the elongating primer, the ddCTP phosphates, and two Mg2+ ions are all
      clustered around Asp190, Asp192, and Asp256. Two of these residues, Asp190 and
      Asp256, are present in the amino acid sequences of all polymerases so far studied
      and are also spatially similar in the four polymerases--the Klenow fragment of
      Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, T7 RNA
      polymerase, and rat DNA pol beta--whose crystal structures are now known. A two
      metal ion mechanism is described for the nucleotidyl transfer reaction and may
      apply to all polymerases. In the ternary complex structures analyzed, pol beta
      binds to the DNA template-primer in a different manner from that recently
      proposed for other polymerase-DNA models.

PMID- 7516581
TI  - Crystal structure of rat DNA polymerase beta: evidence for a common polymerase
      mechanism.
AB  - Structures of the 31-kilodalton catalytic domain of rat DNA polymerase beta (pol
      beta) and the whole 39-kilodalton enzyme were determined at 2.3 and 3.6 angstrom
      resolution, respectively. The 31-kilodalton domain is composed of fingers, palm,
      and thumb subdomains arranged to form a DNA binding channel reminiscent of the
      polymerase domains of the Klenow fragment of Escherichia coli DNA polymerase I,
      HIV-1 reverse transcriptase, and bacteriophage T7 RNA polymerase. The amino
      terminal 8-kilodalton domain is attached to the fingers subdomain by a flexible
      hinge. The two invariant aspartates found in all polymerase sequences and
      implicated in catalytic activity have the same geometric arrangement within
      structurally similar but topologically distinct palms, indicating that the
      polymerases have maintained, or possibly re-evolved, a common nucleotidyl
      transfer mechanism. The location of Mn2+ and deoxyadenosine triphosphate in pol
      beta confirms the role of the invariant aspartates in metal ion and
      deoxynucleoside triphosphate binding.

PMID- 7516582
TI  - Sequestration of GPI-anchored proteins in caveolae triggered by cross-linking.
AB  - Glycosyl-phosphatidylinositol (GPI)-anchored proteins have been reported to
      reside in clusters collected over small membrane invaginations called caveolae.
      The detection of different GPI-anchored proteins with fluorescently labeled
      monoclonal antibodies showed that these proteins are not constitutively
      concentrated in caveolae; they enter these structures independently after cross
      linking with polyclonal secondary antibodies. Analysis of the cell surface
      distribution of the GPI-anchored folate receptor by electron microscopy confirms
      these observations. Thus, multimerization of GPI-anchored proteins regulates
      their sequestration in caveolae, but in the absence of agents that promote
      clustering they are diffusely distributed over the plasma membrane.

PMID- 7516583
TI  - Nicotine on the revascularization of bone graft. An experimental study in
      rabbits.
AB  - STUDY DESIGN: In 24 rabbits, the authors transplanted autologous cancellous bone
      to the anterior chamber of the eye. Half of the rabbits received nicotine and
      half received placebo (albumin) from mini-osmotic pumps that were implanted
      subcutaneously. Revascularization of the bone graft was evaluated postoperatively
      using ophthalmology slit-lamp and fluorescein angiography, and after sacrifice
      using microvascular silicone injection and histology. OBJECTIVES: The hypothesis
      that nicotine inhibits the revascularization of bone graft because of its
      pharmacologic action on the microvasculature was tested. SUMMARY OF BACKGROUND
      DATA: Pseudoarthrosis after spinal fusion occurs more frequently in smokers as
      compared with nonsmokers. METHODS: Observations of the bone graft were made
      regarding the time after implantation when vessels within the graft were noted
      and the pattern of these vessels. Revascularization of the graft was graded based
      on the observed percent area of fluorescence after injection of fluorescein.
      Serum levels of nicotine were measured weekly. Colored silicone was injected at
      sacrifice to fix the vasculature of the bone graft. Histologic analysis of
      undecalcified sections was performed. RESULTS: Nicotine, as compared with
      placebo, was associated with delayed revascularization within the graft, a
      smaller percent area of revascularization, and a larger number of grafts showing
      necrosis. CONCLUSIONS: Nicotine inhibits, but does not prevent, the
      revascularization of cancellous bone grafts. Inhibition of early
      revascularization by nicotine is proposed as the pathophysiologic mechanism by
      which smoking may adversely affect the healing of spinal fusions.

PMID- 7516584
TI  - [Patient admission and induced abortion. The Tuesday meeting].

PMID- 7516585
TI  - [Prostate-specific antigen and prostatic cancer].

PMID- 7516586
TI  - Treatment with FK506 prevents rejection of rat colon allografts.
AB  - Colon transplantation has been proposed as a method to improve the function of an
      intestinal allograft. The present study examined the risk of colon rejection and
      the effect of FK506 on colon rejection in BN-->LEW rats with orthotopic bowel
      transplants. The first 4 groups included rats with untreated allografts (group
      1), rats with isografts treated with 0.6 mg/kg FK506 (group 2), rats with
      allografts treated with 0.6 mg/kg FK506 (group 3), and rats with allografts
      treated with 0.4 mg/kg FK506 (group 4). In each of these groups (10-12 rats),
      half of the animals received a small bowel graft only (SB), while the other half
      received a small bowel, ascending colon, and cecum graft (SBC). The animals were
      followed daily until they died or were killed at 4 weeks. In group 5, an
      additional 18 untreated rats with SBC allografts were randomly killed on the
      third, fifth, seventh, and tenth postoperative days to study the sequential
      histopathologic and immunopathologic changes of colon rejection. There was no
      difference in survival, body weight, nutritional parameters, or bacterial
      contamination after SB and SBC transplantation. Intestinal transit was slower
      after SBC than SB transplantation (P < 0.05). Sequential histopathologic studies
      revealed that (1) the severity and time course of colon rejection was similar to
      small intestine rejection, and (2) the features of colon rejection were similar
      to ulcerative colitis. There was no evidence of graft-versus-host disease after
      SBC transplantation. In summary, adding a segment of large bowel to a small bowel
      allograft does not increase the risk of rejection or surgical complications. The
      transplanted colon slows intestinal transit. Treatment with FK506 effectively
      prevents colon rejection. These data suggest that adding a colon graft may
      improve the outcome of clinical small bowel transplantation.

PMID- 7516587
TI  - An evaluation of the ability of dextrans to reduce acute tubular necrosis during
      cold storage preservation.
AB  - In this study, the ability of low molecular dextrans to prevent morphologically
      detectable acute tubular necrosis during cold storage was evaluated. Rat kidneys
      were flushed with a sodium phosphate buffer (pH 7.2) containing different
      concentrations of dextran 10 (m.w. of 10,000 or less) and stored at 0-2 degrees C
      for up to 5 days (samples taken at 24-hr intervals). It was found that solutions
      containing 20% or more of dextran 10 provided significantly improved
      morphological preservation of kidney nephrons when compared with currently
      popular kidney cold storage preservation solutions (i.e. University of Wisconsin
      and Euro-Collins solutions). Adding smaller amounts (i.e., 15%) of dextran 10 to
      a cold storage solution already containing another effective osmotic agent (i.e.,
      sucrose) also resulted in superior morphological preservation, indicating a
      beneficial additive effect of using more than one osmotic agent. Dextran 40 (m.w.
      40,000) did not provide as good morphological preservation as did a similar
      concentration of dextran 10. It is concluded that the use of the proper kind and
      proper amount of low molecular weight dextrans in preservation solutions can
      significantly reduce the morphologically detectable acute tubular necrosis during
      cold storage.

PMID- 7516589
TI  - A fatal thrombotic complication during liver transplantation after aprotinin
      administration.

PMID- 7516588
TI  - Emergence of inflammatory alveolar macrophages during rejection or infection
      after lung transplantation.
AB  - Local activation of macrophages may play an important role in immune
      complications following lung transplantation. To document such a phenomenon, we
      have investigated the possible changes of alveolar macrophage surface antigen
      expression after lung transplantation. Using immunocytofluorometry, we have
      analyzed the phenotype of alveolar macrophages from 41 bronchoalveolar lavage
      fluids obtained from 19 lung transplant recipients displaying various
      complications. The strong expression of HLA-DR observed on almost all alveolar
      macrophages was similar among groups I (no complication), II (minimal acute
      rejection), and III (mild to severe acute rejection), but was enhanced in group
      IV (bronchial infection) (P < 0.03). We observed no significant variation in the
      monocyte lineage CD14 antigen expression among the 4 groups, and about 83% of
      alveolar macrophages expressed this marker strongly. Membrane expression of the
      27E10 antigen that characterizes infiltrating macrophages in acute inflammatory
      lesions was significantly higher during mild to severe rejection episodes than in
      controls (P < 0.02) and during bronchial infections (P < 0.05) but not during
      minimal rejection. Double staining experiments confirmed that 27E10-positive
      cells in groups III and IV belonged to the macrophage lineage. In addition, the
      expression of the 27E10 antigen on cultured alveolar macrophages was found to be
      increased after stimulation by bacterial lipopolysaccharide or IFN-gamma. These
      results indicate that a particular alveolar macrophage subpopulation is activated
      during immune events after lung transplantation. This population, recognized by
      the 27E10 mAb, might be involved in cytokine production during severe acute
      rejection and infection episodes.

PMID- 7516590
TI  - Postoperative glucose metabolism in liver transplant recipients. A two-year
      prospective randomized study of cyclosporine versus FK506.

PMID- 7516591
TI  - [The cytophotometric determination of the transferrin content of rat hepatocytes
      by using monoclonal antibodies].
AB  - Monoclonal antibodies specifically recognizing rat transferrin were produced.
      Optimal conditions of fixation and carrying out immunocytochemical reaction were
      determined. A combined method is proposed based on the indirect immunoperoxidase
      reaction and Feulgen procedure to be used for studying transferrin contents in
      hepatocytes with different ploidy. The transferrin content increased
      proportionally to the cell ploidy. It is concluded that the cytophotometric
      method may be used for a quantitative study of transferrin content in isolated
      rat hepatocytes.

PMID- 7516593
TI  - [RNA transport in neurons--a new background for understanding of the nervous
      system plasticity?].

PMID- 7516592
TI  - [Diagnosis and treatment of acute sinusitis by Danish general practitioners].
AB  - We studied Danish general practitioners' (GP) weighting of symptoms, clinical
      findings and use of paraclinical investigations when diagnosing acute sinusitis
      in adults. Questionnaires were sent to 300 representative GPs. Sixty-seven
      percent answered the questionnaire. The GPs weighted pain and tenderness on
      application of pressure over the sinuses as the most important symptom and
      finding. Only a few used paraclinical investigations. The GPs estimated their own
      diagnostic certainty as being 70%. Detumescent nose-drops were prescribed in 95%
      of the cases, and antibiotic treatment was given in 50%, most frequently as V
      penicillin.

PMID- 7516594
TI  - Improved sensitivity in the diagnosis of dermatophytosis by fluorescence
      microscopy with calcafluor white.

PMID- 7516595
TI  - Location of antibody epitopes within the mouse hepatitis virus nucleocapsid
      protein.
AB  - Thirteen monoclonal antibodies (Mab) specific for the nucleocapsid (N) protein of
      mouse hepatitis virus were mapped using a panel of carboxy-terminal N protein
      truncations expressed by recombinant vaccinia viruses. All of the Mab recognized
      both native protein and full-length N protein expressed in this vector by both
      Western blot and enzyme-linked immunoabsorbent assays (ELISA), indicating that
      they recognized linear epitopes. The results obtained by both Western blot and
      ELISA for binding to the truncated N proteins coincide for seven of the Mab
      tested. The linear epitopes recognized localize to four domains dispersed between
      amino acids 171 and 196, 231 and 277, and 374 and 455. The epitopes for six Mab
      were localized to domains comprising 29 amino acids or less as determined by
      ELISA. Seven Mab showed different reactivity patterns in Western blot versus
      ELISA, suggesting binding may be influenced by local conformation. Therefore, the
      fine specificity of these Mab could not be determined with certainty. These data
      represent the first determination of antibody binding domains within the mouse
      hepatitis virus N protein which forms the viral helical nucleocapsids and appears
      to perform a number of regulatory functions during virus replication.

PMID- 7516596
TI  - Sequence requirements for Rev multimerization in vivo.
AB  - Multimerization of the human immunodeficiency virus type 1 (HIV-1) Rev protein is
      believed to be critical to its biological activity. However, the precise protein
      sequence requirements for Rev multimerization in vivo, and whether
      multimerization is facilitated by specific RNA binding or vice versa, has
      remained controversial. In this report, we describe a sensitive in vivo assay for
      the multimerization of HIV-1 Rev on its cognate RRE primary RNA binding site.
      Using this assay, we demonstrate that an intact Rev arginine-rich domain, while
      critical to specific RNA binding, is dispensable for multimerization on the RRE.
      Mutations introduced into Rev sequences that flank this basic domain produce a
      partial multimerization phenotype in vivo even though these mutations are known
      to block Rev multimerization in vitro. Similarly, mutations introduced into the
      leucine-rich activation domain of Rev, which appear to have no effect on in vitro
      multimerization, also markedly inhibit multimerization of Rev on the RRE in vivo.
      Overall, these data appear consistent with the hypothesis that in vivo formation
      of the multimeric Rev:RRE ribonucleoprotein complex is facilitated by both the
      RRE RNA substrate and, as first proposed by Bogerd and Greene U. Virol. 67, 2496
      2502, 1993), by bridging by a cellular cofactor for Rev that likely interacts
      with multiple Rev activation domains.

PMID- 7516597
TI  - The flavivirus nonstructural protein NS3 is a dominant source of cytotoxic T cell
      peptide determinants.
AB  - Vaccinia virus recombinants encoding regions of the Murray Valley encephalitis
      virus (MVE) genome, which together cover the entire viral coding region, were
      employed to identify the MVE protein which is the dominant source of CD8+,
      cytotoxic, T cell antigenic determinant(s) presented by the mouse H-2Kk major
      histocompatibility antigen. MVE and West Nile virus-immune, H-2k-restricted,
      effector cells recognized peptides derived from the MVE nonstructural polyprotein
      segment, and in this region the immunodominant determinant mapped to protein NS3.
      Interestingly, mapping of cytotoxic T cell antigenic determinants of other
      flaviviruses also identified the NS3 protein as the dominant source of antigenic
      peptides (A. B. Hill, A. Mullbacher, C. Parrish, G. Coia, E. G. Westaway, and R.
      V. Blanden, 1992, J. Gen. Virol. 73, 1115-1123; A. L. Rothman, I. Kurane, C.-J.
      Lai, M. Bray, B. Falgout, R. Men, and F. A. Ennis, 1993, J. Virol. 67, 801-806).
      Using an allele-specific peptide motiff for H-2Kk, we predicted 12 peptides in
      the MVE NS3 protein as ligands for the restriction element and identified three
      peptides which were recognized in association with H-2Kk by MVE-immune cytotoxic
      T cells. We also examined the effect of proteolytic processing in the MVE
      nonstructural polyprotein segment mediated by the viral proteinase NS3 on antigen
      processing and presentation of the MVE H-2Kk-restricted T cell determinant.
      Processing of the MVE polyprotein by the viral proteinase did not markedly
      influence the availability of this peptide determinant.

PMID- 7516598
TI  - Neutron diffraction reveals the site of amantadine blockade in the influenza A M2
      ion channel.
AB  - The influenza A M2 protein forms proton channels which are blocked by the anti
      influenza drug amantadine. Using the technique of neutron diffraction with both
      deuterium-labeled amantadine and influenza A M2 peptides, this study has directly
      located the position of interaction between the drug and the transmembrane domain
      of M2. Amantadine is found 0.5 nm from the center of the bilayer in an area
      between Val 27 and Ser 31, a location consistent with the formation of a steric
      block within the ion channel. Similar experiments with amantadine and an
      amantadine-resistant mutant peptide showed no such interaction.

PMID- 7516599
TI  - Bovine leukemia virus induces CD5- B cell lymphoma in sheep despite temporarily
      increasing CD5+ B cells in asymptomatic stage.
AB  - To investigate bovine leukemia virus (BLV)-induced leukemogenesis, we infected
      sheep with BLV and used flow-cytometric and immunohistological analysis to
      characterize the phenotypic alterations in lymphocytes from peripheral blood and
      lymph nodes taken from the animals with lymphoma at various stages. In sheep at
      the asymptomatic stage, depending on the extent of progression of the disease,
      the proportions of CD2(+)-, CD4(+)-, CD8(+)-, and gamma delta TCR(+)-T cells that
      coexpressed CD5 decreased, but CD5+ sIgM+ cells as well as CD5- sIgM+ cells
      increased for a period. The number of CD5+ B cells, however, rapidly decreased in
      the lymphoma stage. On the other hand, neoplastic lymphocytes appeared to be a
      monoclonal population derived from a single cell with surface phenotypes of
      sIgM+, B-cell-specific molecule B2+, major histocompatibility complex (MHC) class
      II+, OvCD5-, OvCD2-, OvCD4-, OvCD8-, gamma delta TCR-, which suggests that only
      CD5- B cells proliferate clonally when the disease proceeds to the lymphoma
      stage. Thus, rapid decrease of CD5+ B cells may be used as a marker of lymphoma
      stage. To identify the BLV provirus in the CD5- B and CD5+ B cells throughout the
      course of disease, each fraction of CD5- B and CD5+ B cell was sorted from the
      peripheral blood by flow cytometry and nested double polymerase chain reaction
      was performed. In BLV-infected but healthy sheep, BLV integrated both CD5- B and
      CD5+ B cells. In lymphoma, however, BLV provirus was detected only in CD5- B
      cells but not in CD5+ B cells. Therefore it appears that a disappearance of BLV
      infected CD5+ cells is one of the critical events leading to CD5- B cell lymphoma
      in sheep. This is in contrast to the BLV-induced lymphoma in cattle which shows
      CD5+ phenotype.

PMID- 7516600
TI  - Cytotoxic T lymphocyte responses to the envelope proteins of endogenous ecotropic
      and mink cytopathic focus-forming murine leukemia viruses in H-2b mice.
AB  - To study the possible role of immune selection in the in vivo generation of
      pathogenic recombinant murine leukemia viruses (MuLV), we have constructed
      recombinant vaccinia viruses (rVV) expressing the envelope genes of three MuLV:
      AKR623, MCF247, and MCF13. rVV expressing either AKR623 or MCF247 env could prime
      H-2b mice for anti-AKR/Gross virus CTL responses, and stimulate the in vitro
      generation of CTL from the spleens of mice immunized with an AKR/Gross virus
      positive lymphoma. MC57 (H-2b) cells infected with either 623EnvVac or 247EnvVac
      could serve as targets for ARK/Gross virus-specific CTL. Cells infected with the
      rVV expressing MCF13 env, however, were lysed much less efficiently by these CTL.
      13EnvVac was also ineffective in priming or stimulating retrovirus-specific CTL.
      Finally, experiments with synthetic peptides and minigenes suggested that the
      reduced immunogenicity of the MCF13 envelope protein likely resulted from a
      single amino acid substitution within an immunodominant epitope of the p15E (TM)
      protein. The region of MCF13 env that encodes this epitope is derived from an
      endogenous xenotropic virus, while the allelic sequences in MCF247 are of
      ecotropic virus origin. These results suggest the potential for recombination
      within the MuLV envelope gene to allow escape from host cellular immune
      responses.

PMID- 7516601
TI  - Expression of the myelin basic protein gene in transgenic mice expressing human
      neurotropic virus, JCV, early protein.
AB  - Transgenic mice containing the early region of the JC virus encoding T-antigen
      developed neurological disease resulting from dysmyelination in the central
      nervous system. In this study, we investigate expression of the myelin basic
      protein (MBP) gene, a major constituent of the myelin sheath, at the RNA level by
      Northern blot and S1 nuclease assay and at the protein level by Western blot
      analysis using anti-MBP antibody in two distinct transgenic lines exhibiting
      different degrees of dysmyelination. Results from Western blot analysis of
      proteins from the brains of these mice revealed great reductions in MBP levels
      that parallel the severity of dysmyelination in the corresponding animals.
      Analysis of MBP RNA by Northern and quantitative S1 assays exhibited no
      alterations in the transcription initiation sites of the MBP gene in these
      animals; however, a significant decrease in the level of MBP mRNA was detected,
      suggesting that T-antigen may negatively influence transcription of the MBP gene.
      Results from Northern and Western blot analysis of proteolipid protein revealed
      low-level expression of this gene. Expression of JCV T-antigen is developmentally
      regulated in the transgenic mice; it appears at 8 days postnatal, peaks at 15
      days, and substantially decreases in 18-day-old mice. The programmed expression
      of JCV T-antigen, which overlaps with MBP gene transcription at the early stage
      of myelination, suggests the involvement of a pathway which modulates stage
      specific regulation of myelin genes and viral gene expression in transgenic mice
      during brain development.

PMID- 7516602
TI  - The value of prostatic specific antigen in prostate cancer screening in the
      community.
AB  - At a one-day screening for prostate cancer in 1991, a urologist evaluated 142 men
      ages 50 years-84 years (mean: 67 years) utilizing a digital rectal exam (DRE),
      serum prostatic specific antigen (PSA), and a detailed questionnaire. The 44 men
      with an abnormal DRE and/or PSA were recontacted by letter one year later to
      determine the outcome. By 12 months, 31 men (70%) with abnormal findings had seen
      a physician as recommended. Of the 13 men followed with abnormal DRE only, three
      were biopsied with no cancer found. Of the 11 with an elevated PSA only, six were
      biopsied and two had cancer. Of the men with both abnormal PSA and DRE, six were
      biopsied and two had cancer. Thus, after 12 months, the preliminary cancer
      detection rate was 2.8% for the entire study population, 22% for those with an
      elevated PSA, and 10% for those with an abnormal DRE. The results suggest that
      the use of PSA combined with DRE is a more efficient strategy for detecting
      prostate cancer than DRE alone.

PMID- 7516603
TI  - [Pediatric dysphasia. II. The current concepts of its neurobiological
      mechanisms].
AB  - This survey deals with the underlying biological causes and pathogenetic
      mechanisms of developmental dysphasia. There can be a basic syndrome of "pure
      dysphasia"; these children are very likely to have a genetically determined
      developmental disorder on a limited neuronal level (no cerebral damage of any
      kind) on a developmental disorder by other factors such as an abnormal cortical
      architecture and abnormal symmetry of the hemispheres. In somewhat more than half
      the patients, the basic syndrome of pure dysphasia is accompanied by other
      neurological signs, most of which are indicative of functional disorders of the
      left hemisphere. There can also be symptoms of the right hemisphere, of the
      corpus callosum and of the afferent pathway systems for auditory perception. The
      nature and causes of these anomalies can be multifarious, so that it is
      unfeasible to speak of the substrate or the pathogenesis.

PMID- 7516604
TI  - [Effects of praeruptorin-C on cytosolic free calcium in cultured rat heart
      cells].
AB  - The negative inotropic effect of Pra-C was supposed to be related to the blocking
      of extracellular calcium influx but direct evidence is not known. We, therefore,
      examined the effects of Pra-C on [Ca2+]i in isolated rat ventricular myocytes
      using the fluorescent Ca(2+)-indicator Fura-2/AM. It was found that Pra-C
      inhibited the elevation of [Ca2+]i induced by potassium-depolarization, high
      extracellular calcium and calcium agonist Bay K 8644 in a dose-dependent manner.
      At 1.0 mumol.L-1, it decreased the [Ca2+]i at the presence of 75 mmol.L-1 KCl, 10
      mol.L-1 CaCl and 3 mumol.L-1 Bay K 8644 by 50, 31 and 42% respectively. No
      significant effect on ouabain evoked [Ca2+]i increase was found, showing that it
      does not affect sarcolemmal Na(+)-Ca2+ exchange. These results further indicate
      that Pra-C may decrease the [Ca2+]i of myocyte by blocking voltage-dependent
      calcium channels.

PMID- 7516606
TI  - [Studies on pharmacologic disposition of adriamycin in dog after hepatic arterial
      embolization with adriamycin carboxymethyl-dextran-microspheres].
AB  - The ion exchange adriamycin carboxymethyl-dextran-microspheres (AD-CM-DMS) was
      chosen as a model preparation. Pharmacokinetics, targeting and embolization
      effects of the microspheres were studies after hepatic arterial embolization in
      vivo in dogs. After hepatic arterial infusion, the concentrations of ADM in
      peripheral vein blood and hepatic tissue were determined by HPLC. The peak
      concentrations were (0.558 micrograms/ml for AD-CM-DMS and 1.013 micrograms/ml
      for ADM solution. T1/2 (alpha), T1/2 (beta) and MRT of AD-CM-DMS were
      respectively 2.82, 3.19 and 1.28 times as much as those of ADM solution. At the
      target site, the tissue concentrations of AD-CM-DMS were respectively 8.0 and 9.1
      times those of ADM solution. The dynamic vessel angiography revealed no external
      and internal collaterals and no complete degradation of AD-CM-DMS after sixteen
      weeks was observed. These results suggest that AD-CM-DMS are useful as embolic
      agent for the treatment of hepatic cancer. It could facilitate intensive
      chemotherapy with minimum systematic side effect.

PMID- 7516607
TI  - Proceedings of the 2nd international symposium on ion channels and calcium
      antagonists (ISICCA). 1993 Nov 9-12. Abstracts.

PMID- 7516605
TI  - [Effects of linesinine on slow action potentials in myocardium and slow inward
      current in canine cardiac Purkinje fibers].
AB  - Standard microelectrode and two-microelectrodes voltage clamp techniques were
      used to study the effects of linesinine (Lien), an alkaloid extracted from the
      green seed embryo of Nelumbo nucifera Gaertn, on slow action potentials (AP) and
      slow inward current (Isi). Lien 10-100 mumol/L was shown to concentration
      dependently decrease the action potential amplitude (APA), the maximal velocity
      of phase 0 depolarization (Vmax) and prolong the sinus cycle length (SCL) of slow
      AP in isolated sinoatrial node (SAN) pacemaker cells of rabbits. On both slow APs
      of rabbit SAN cells and guinea pig papillary muscles partly depolarized by high
      K+, Bay K 8644 0.03 mumol/L markedly increased the APA and Vmax, which were
      obviously antagonized by Lien 10 mumol/L. Moreover, Lien 1-100 mumol/L was found
      to inhibit the Isi of canine cardiac Purkinje fiber in concentration-dependent
      manner. Lien 3 and 100 mumol/L reduced the peak value of Isi by 14% and 88%
      respectively. The results suggest that Lien possesses calcium antagonistic
      effects.

PMID- 7516608
TI  - Whole-cell patch clamp measurements and berberine inhibition of hyperpolarization
      activated inward current in rabbit sinoatrial node cells.
AB  - Single rabbit sinoatrial node (SAN) cells were isolated by means of an enzymatic
      dispersion procedure and used for the whole-cell patch clamp experiment. At a
      holding potential of -40 mV, a time- and voltage-dependent inward current, I(f),
      was activated at different hyperpolarization potentials from -60 mV to -110 mV.
      The current-voltage relation curve showed that I(f) was activated at potential
      more negative than -40 mV. Five min after treatment by CsCl 2 mmol.L-1-containing
      Tyrode solution, I(f) was almost completely blocked. At a hyperpolarization
      potential of -110 mV, I(f) was reduced from 1.7 +/- 0.2 nA of the control to 1.2
      +/- 0.4 nA after superfusing with Tyrode solution containing berberine (Ber) 1
      mumol.L-1 for 5 min. And it was difficult to wash out this action. Ber also had
      inhibitory effects on other currents to a certain extent. The results indicate
      that I(f) is a Cs(+)-sensitive current and that the negative chronotropic effect
      of Ber may be due to the inhibition of I(f) that functions as an important
      pacemaking modulator for the spontaneous depolarization of SAN tissue.

PMID- 7516609
TI  - Effects of nicotinamide on cardiac contraction force and slow inward current.
AB  - The effects of nicotinamide (Nic) on cardiac contraction force and on slow inward
      current (Isi) in guinea pigs were studied with atrial strips and voltage clamp
      techniques. Verapamil (Ver), MnCl2, nifedipine (Nif), and propranolol (Pro)
      depressed markedly the positive inotropic effect induced by Nic in a
      noncompetitive manner. The pD2 values of Ver, MnCl2, Nif, and Pro were 6.19,
      3.41, 5.00, and 6.43, respectively. The action of Nic was reduced by a low Ca2+
      Tyrode solution and disappeared in a Ca(2+)-free solution. Nic 33 mmol.L-1
      elevated the Isi from 6.5 +/- 1.3 microA to 10.3 +/- 2.2 microA. The results
      suggest that Nic promotes the Ca2+ influx and its site of action is different
      from that of both Pro and the calcium antagonists.

PMID- 7516610
TI  - Effects of aprotinin in platelet aggregation and cytosolic free calcium in swine
      platelets.
AB  - Aprotinin inhibited platelet aggregation induced by thrombin (0.25 U.ml-1) with
      IC50 200 kIU.ml-1, and inhibited the rise of cytosolic free calcium concentration
      in platelets stimulated by thrombin (0.1 U.ml-1) in the absence and in the
      presence of Ca2+ 0.5 mmol.L-1 (IC50 117 and 50 kIU.ml-1, respectively), but had
      no effect on the amounts of actin and myosin heavy chain associated with
      cytoskeletons. These suggest that aprotinin is an anti-platelet agent and may
      exert its action through inhibiting the Ca2+ flux.

PMID- 7516611
TI  - [Single channel analysis on calcium channel blockade action of panaxadiol and
      panaxatriol saponins on cultured rat ventricular myocytes].
AB  - Wistar rat ventricular myocytes were isolated. Panaxadiol saponins 1500
      micrograms.ml-1, panaxatriol saponins 300 micrograms.ml-1, verapamil 37.5
      micrograms.ml-1, or BAY k 8644 5 mumol.L-1 were added into the bath solution
      separately. The single channel activities of L, T, and B type calcium channels
      were recorded before and after the administration, using voltage patch-clamp
      technique in cell-attached configuration. The calcium channel blockade effect of
      these 2 groups of ginsenosides was authenticated verified. The mechanism existed
      in the decrease in both the open time and the open-state probability of the
      calcium channel.

PMID- 7516612
TI  - [Drug resistance of doxorubicin-resistant CHO cell line].
AB  - Some characteristics of doxorubicin-resistant CHO cell line (RC1) were studied by
      means of cell biological methods and SDS-PAGE electrophoresis. The resistance
      factor was 16.5-fold, and RC1 revealed cross-resistances to colchicine,
      actinomycin and harringtonine. By indirect immunofluorescence assay, P
      glycoprotein was not detected. Compared with CHO, the doxorubicin (Dox) uptake
      and accumulation of RC1 decreased, but the membrane fluidity of RC1 increased.
      The reduction in drug accumulation was correlated with increase in membrane
      fluidity. Dox was mainly distributed in the cell nucleus of CHO, but in both
      cytoplasm and nucleus of RC1. This suggested that Dox was transported more slowly
      in RC1 cytoplasm than in CHO cytoplasm, resulting in less Dox entrance into the
      cell nucleus of RC1 than into that of CHO. We also found that a 30-40 kDa nuclear
      protein which was expressed normally in CHO disappeared in RC1.

PMID- 7516613
TI  - Chondrocytes of the adult rat express mRNA for insulin-like growth factor binding
      protein-4 (IGFBP-4).

PMID- 7516614
TI  - Phage-related conversion of enterotoxin A, staphylokinase and beta-toxin in
      Staphylococcus aureus.
AB  - The conversion of enterotoxin A, staphylokinase and beta-toxin in Staphylococcus
      aureus is related with lysogeny stage. Bacteriophages able to convert enterotoxin
      A were used for lysogenization of the standard NCTC 8325-4 strain. Lysogenic,
      enterotoxigenic derivatives of this strain were characterized. The conversion of
      enterotoxin A was obtained in 7 examined derivatives, the conversion of
      enterotoxin A and staphylokinase at the same time was obtained in one case and
      the loss of beta hemolysin production ability was observed in all of 8 examined
      derivatives of the NCTC 8325-4 standard strain.

PMID- 7516615
TI  - Synergistic effect of cefotaxime and normal human serum on bactericidal activity
      against urinary strains of Escherichia coli with capsular antigen K1.
AB  - About 11% of Escherichia coli strains isolated from patients with urinary tract
      infections produced capsular antigen K1. In a group of strains resistant to
      normal human serum the percentage of strains with K1 antigen was higher than that
      without this antigen. Cefotaxime and serum showed synergistic action in the
      bactericidal reaction against E. coli strains resistant to the serum. Lack of
      synergistic effect of thermally inactivated serum with subminimal concentrations
      of cefotaxime indicated participation of complement in this reaction. The
      antibiotic used in subminimal concentrations caused significant elongation of E.
      coli bacilli.

PMID- 7516616
TI  - Comparison of Delmee and Polish serogroup-specific Clostridium difficile strains.
AB  - In this study we compared Delmee and Polish serogroup-specific Clostridium
      difficile strains by slide agglutination, observation of flagella and SDS-PAGE
      protein patterns. Among Delmee serogroup specific strains we observed flagella in
      groups A, D and K. Among Polish serogroup-specific Clostridium difficile strains
      we did not observe flagella. The Polish serogroup-specific strains gave different
      protein patterns compared to Delmee strains. SDS-PAGE protein pattern analyses of
      Polish serogroup-specific strains divide these strains into 3 groups: 71, 88 and
      third embracing 18, 27, 70, 72, and 89.

PMID- 7516617
TI  - Epidemiological estimation of Pseudomonas aeruginosa strains isolated from
      different environments.
AB  - 117 P. aeruginosa strains have been isolated from hospital material (vascular
      ward), from ambulatory patients, from lake water samples and from animal
      environment. The serological characters of the above strains, their phage--typing
      patterns, their capability of producing ONPG hydrolase were compared in order to
      find out the strain with identical features responsible for nosocomial infections
      and also to find endemic infections. There were eleven polyagglutinable strains
      (isolated from sinks in the vascular ward) which agglutinated with two sera and
      one strain isolated from lake water. Apart from one exception there were no
      confirmations of the occurrence of the strains of identical features in different
      environments. Possible variability within the scope of somatic antigen and the
      phage typing of microorganism confirm the necessity to use several techniques to
      carry out studies of epidemiological significance.

PMID- 7516618
TI  - A study of purified pyocyanine produced by Pseudomonas aeruginosa: properties and
      grouping.
AB  - A study of more than one thousand strains of Pseudomonas aeruginosa was
      performed. These were collected from different sources, i.e. humans, animals,
      environment and food. Cumulative results revealed the existence of three
      different groups of pyocyanine. The biological importance of grouping this
      pigment is due to its activity against other bacteria in comparison with other
      antibiotics such as cyanomycin produced by Streptomyces cyanoflavus. No such
      grouping or any other classification was found in the literature. Stability test
      and MIC (minimum inhibitory concentration) measurements revealed the priority of
      group (I); also isolates of animal origin were found preferable. This may be due
      to the resistance of strains isolated from animals to antibiotics especially to
      carbenicillin and gentamycine. Observations indicate differences in optical
      properties of the blue pigment, i.e. absorption centres in the UV region. Some
      differences in their physical properties were also noted.

PMID- 7516619
TI  - Fungi in activated sludge biocenosis.
AB  - It has been found that yeasts and yeast-like microorganisms are stable
      constituents of activated sludge biocenosis treating municipal wastewaters with a
      mixture of different industrial wastewaters at B upsilon values in the range of
      1.3-1.7 kg COD m-3day-1 and B chi = 0.22-0.42 kg COD kg-1day-1. The number of
      these microorganisms reached about 10(4) cells mg VSS-1 and as typical species
      Saccharomyces cerevisiae and Candida famata can be considered. Considerably less
      numerous (4-8 cells mg VSS-1) was the mycoflora of high loaded treatment systems
      of petrochemical wastewaters (B upsilon = 10.3-14.1 kg COD m-3day-1 and B chi =
      1.06-1.92 kg COD kg-1day-1) and municipal wastewaters with a mixture of aromatic
      amines (B upsilon = 1200-2400 mg COD l-1 day-1 and B chi = 0.43-0.94 mg COD mg
      1day-1). Typical species for these sludges were Geotrichum candidum, G.klebahnii,
      G.sericeum, Trichosporon cutaneum and Sporobolomyces lactosus.

PMID- 7516620
TI  - Ozone as sensitizer of bacteria to the bactericidal action of complement.
AB  - The purpose of this study was to answer the question whether the exposure of
      bacterial cells to ozone results in changes of their sensitivity to the
      bactericidal action of normal bovine serum (NBS). Our initial studies have
      demonstrated that contact of bacteria with O3 enhances serum-mediated killing.

PMID- 7516622
TI  - In vitro translation of fractionated virus-specific RNA isolated from plasma of
      chicken infected by avian myeloblastosis virus. Unprocessed and processed
      myeloblastosis-associated virus env-polypeptide precursors.
AB  - The 60 S viral RNA complex isolated from leukaemic plasma of chicken infected by
      avian myeloblastosis virus (AMV) was denatured, the poly(A)-RNA selected and
      centrifuged in a linear sucrose density gradient. RNA from each fraction was
      translated in vitro and the products were analyzed by slab polyacrylamide gel
      electrophoresis (PAGE). Unprocessed primary translation product (p64env) of MAV
      env gene from 21 S RNA fraction was immunoprecipitated by anti-gp85 serum. If,
      however, this RNA was translated in the presence of dog pancreas microsomal
      membranes (DPM), the processed 92 K MAV glycoprotein precursor (p92env) was
      immunoprecipitated by anti-gp85 serum. This precursor, unlike p64env was
      resistant to exogenous protease.

PMID- 7516621
TI  - Analysis of computer-predicted antibody inducing epitope on Japanese encephalitis
      virus.
AB  - Theoretical methods to delineate antibody inducing epitopes have been employed to
      predict antigenic determinants on envelope glycoprotein (gpE) of Japanese
      encephalitis (JE), West Nile (WN) and Dengue (DEN) I-IV viruses. A predicted
      region on JE virus gpE 74CPTTGEAHNEKRAD87 was synthesized, conjugated to KLH (KLH
      peptide) and used in immunization of mice. A mouse monoclonal antibody (MoAb
      IVB4) reactive to the peptide was also found to react with native JE virus gpE.
      Characterization of the idiotypic (ID) determinants with the help of polyclonal
      domain-specific anti-ID antibodies revealed that polyclonal anti-KLH-peptide
      antibodies and MoAb IVB4 are flavivirus-cross-reactive to Hx and NHx domains,
      respectively. The region 74-87 in JE virus gpE has been mapped as a linking area
      between Hx and NHx domains. Reactivity of the peptide with sera from JE patients
      and vaccinees also indicated the feasibility of using predicted peptides for
      diagnostic and prophylastic purposes.

PMID- 7516623
TI  - Assessment of exposure to arsenic among smelter workers: a five-year follow-up.
AB  - In a group of 43 smelter workers exposed to inorganic arsenic dust for 13-45
      years, nerve conduction velocities (NCVs) were significantly lower in two
      peripheral nerves as compared with matching referents. With multivariate data
      analysis, a significant negative correlation was found between cumulative
      absorption of arsenic and NCV in four examined nerves and the sural amplitude.
      Clinical symptoms of neuropathy and other symptoms related to arsenic exposure
      were moderate, though the difference between the groups was significant. The mean
      total absorption of arsenic was calculated to be less than 5 g, and the maximal
      absorption about 20 g. These data indicate that the adverse effect of arsenic on
      the peripheral nerves is dependent on long-term exposure rather than on short
      term fluctuations in exposure levels.

PMID- 7516624
TI  - Mortality among taxi drivers in Rome: a cohort study.
AB  - The mortality pattern of taxi drivers in Rome as possibly exposed mainly to
      gasoline engine exhausts was evaluated by means of a historical cohort study. A
      total of 2,311 male subjects registered as taxi drivers between 1950 and 1975 was
      followed from 1965 through 1988. The overall mortality was lower than expected on
      the basis of regional (Latium) reference rates (692 deaths, standardized
      mortality ratio [SMR] = 0.89, 95% confidence interval [CI] 0.82-0.96), whereas
      the number of recorded deaths for malignant neoplasms was about the expected (205
      deaths, SMR = 0.99, 95% CI 0.86-1.13). Mortality from circulatory and respiratory
      diseases was lower than expected. Diabetes was significantly increased (42
      deaths, SMR = 1.73, 95% CI = 1.25-2.34). An increased SMR appeared for
      respiratory cancer (SMR = 1.23, 95% CI = 0.98-1.50), mainly due to lung cancer
      (observed [O] = 76, SMR = 1.23, 95% CI = 0.97-1.54); two pleural cancers were
      also recorded. The excess of lung cancer deaths was present only among those
      enrolled in the most recent period (1965-1975) (45 deaths, SMR = 1.40, 95% CI =
      1.02-1.87), especially among those of younger age (< 65 years) (SMR = 1.86);
      there was no relation between lung cancer mortality and latency since first
      enrollment in the cooperatives or duration of membership. There are difficulties
      in interpreting the excess of lung cancer on the basis of occupational exposures;
      however, the increased risk observed among workers employed in more recent
      calendar periods may be due to heavier exposure in the last decades; further
      follow-up of the cohort may elucidate whether there is an increasing lung cancer
      risk among taxi drivers.

PMID- 7516625
TI  - Duplication 20p identified via fluorescent in situ hybridization.
AB  - A 3-year-old girl is reported with dup (20p) resulting from 3:1 segregation of a
      de novo t(20;21). The proposita presented with minor anomalies, developmental
      delay, a clinical phenotype suggestive of 20p trisomy, and a karyotype with a
      21p+ and an additional small marker chromosome. Conventional cytogenetic
      techniques were not informative for the identification of the origin of the extra
      material of chromosome 21p nor for the marker chromosome. The 21p+ and marker
      chromosomes were successfully characterized using fluorescent in situ
      hybridization (FISH).

PMID- 7516627
TI  - Cerebral blood flow in primates is increased by isoflurane over time and is
      decreased by nitric oxide synthase inhibition.
AB  - BACKGROUND: Cerebral blood flow (CBF) decreases over time in dogs and goats
      during volatile anesthesia. In the current study, we determined CBF during
      administration of isoflurane for 4 h in cynomolgus monkeys. In addition, we
      determined if nitric oxide (NO) contributes to cerebrovascular tone during
      isoflurane anesthesia by determining the CBF (microsphere) response to inhibition
      of NO synthase with N omega-nitro-L-arginine methyl ester (L-NAME). METHODS: CBF
      was measured in five monkeys anesthetized with isoflurane (1.0% end-tidal). After
      4 h of isoflurane (1.0% = 1 MAC), the effects of intravenous L-NAME (60 mg/kg
      over 10 min) followed by intravenous L-arginine (600 mg/kg over 10 min) on CBF
      were measured at constant cerebral perfusion pressure and arterial carbon dioxide
      tension. RESULTS: CBF was unchanged over time (4 h) in cerebellum but increased
      by 50 +/- 18% in both forebrain and hindbrain (P < 0.05). CBF decreased by 41-48%
      (P < 0.05) 20 min after L-NAME in forebrain, cerebellum, and hindbrain, at which
      time brain NO synthase activity was less than 10% of baseline. Twenty minutes
      after L-arginine, CBF was increased in cerebellum by 32 +/- 8% and in forebrain
      by 41 +/- 9% (P < 0.05). The cerebral metabolic rate of oxygen consumption was
      unaffected by time or by L-NAME or L-arginine. CONCLUSIONS: These data
      demonstrate that CBF increases over time during isoflurane anesthesia in
      primates. Tonic production of NO contributes to control of CBF in primates during
      isoflurane anesthesia. Increased CBF by L-arginine after L-NAME supports the
      hypothesis that L-NAME decreases CBF via a mechanism requiring NO synthesis.

PMID- 7516629
TI  - Evidence of linkage between high-glycine-tyrosine keratin gene loci and wool
      fibre diameter in a Merino half-sib family.
AB  - Candidate genes for quantitative trait loci have been studied in a Medium Peppin
      Merino flock. Obvious candidates for effects on wool production traits are genes
      for the major proteins expressed in the wool fibre, the keratin and keratin
      associated protein genes. Two keratin-associated protein loci, KRTAP6 and KRTAP8,
      have previously been shown to be linked. The results of analyses between these
      two loci and production traits gave significant evidence of linkage with wool
      fibre diameter in one out of eight half-sib groups tested. High-glycine-tyrosine
      proteins (KRTAP6, 7 and 8) are known to vary considerably in abundance in wool
      fibres and it is possible that a gene for major effect on fibre diameter is
      located within the same chromosomal region as KRTAP6 and KRTAP8.

PMID- 7516626
TI  - Growth hormone (GH), insulin-like growth factors (IGFs), and IGF-binding protein
      3 (IGFBP-3) in a child with Proteus syndrome.
AB  - Proteus syndrome is a congenital hamartomatous disorder characterized by partial
      overgrowth involving all germ layers. A somatic mutation model has been proposed
      since familial cases are extremely rare. We report on a 3-year-old girl with
      typical manifestations of Proteus syndrome, including local, asymmetric
      hypertrophy of various parts of the body. Total body length was reduced. Serum
      levels of IGF-I and especially IGF-II and their major growth hormone dependent
      binding protein (IGFBP-3) were significantly reduced, although growth hormone
      secretion after a pharmacological stimulus was normal. In vitro studies of
      fibroblasts derived from hypertrophied tissue showed normal IGF-I production and
      somewhat reduced IGF-II and IGFBP-3 production as compared to normal human skin
      fibroblasts. Affinity cross-linking experiments showed that fibroblasts of the
      affect tissue in Proteus syndrome produced an unusual pattern of IGF bindings
      proteins containing large amounts of an IGFBP with high affinity to IGF-II. The
      data suggest that IGF production is generally disturbed in Proteus syndrome with
      imbalanced levels of specific IGFBP in affected tissue.

PMID- 7516628
TI  - Nitric oxide and prostanoids contribute to isoflurane-induced cerebral hyperemia
      in pigs.
AB  - BACKGROUND: The mechanism of isoflurane-induced cerebral hyperemia is poorly
      understood. Data from studies in vitro suggest that volatile anesthetics release
      a vasodilator prostanoid. We hypothesized that prostanoids and nitric oxide (NO)
      are mediators of this response in vivo. If true, inhibition of cyclooxygenase by
      indomethacin (5 mg/kg intravenously) or of nitric oxide synthase by N omega-nitro
      L-arginine methyl ester (L-NAME; 40 mg/kg intravenously) should attenuate
      isoflurane-induced hyperemia. Any response to L-NAME occurring via nitric oxide
      should be competitively reversed by L-arginine. METHODS: The cerebral blood flow
      (microsphere) response to 1 MAC isoflurane was tested at three time points (0,
      90, and 180 min) in pentobarbital-anesthetized pigs. Isoflurane challenges were
      separated by 60-min periods of continuous intravenous pentobarbital alone.
      Control animals (n = 7) received no additional pharmacologic intervention.
      Experimental animals were randomized to receive L-NAME before the second and
      indomethacin before the third isoflurane challenge (n = 7); L-NAME before the
      second and L-arginine (400 mg/kg intravenously) before the third isoflurane
      challenge (n = 9); or indomethacin before the second and L-NAME before the third
      isoflurane challenge (n = 8). RESULTS: In control animals, isoflurane
      reproducibly increased cerebral blood flow (whole brain; 113 +/- 18%, 120 +/-
      18%, and 103 +/- 19% increase above baseline at each time point, respectively).
      Both indomethacin and L-NAME attenuated (10 +/- 10% and 52 +/- 11% increase,
      respectively) the hyperemic response to isoflurane. The effect of L-NAME was
      reversed by L-arginine. CONCLUSIONS: We conclude that both prostanoids and nitric
      oxide contribute to isoflurane-induced hyperemia. We are unable to determine from
      our data what, if any, interaction exists between these two mechanisms.

PMID- 7516633
TI  - Effectiveness of poloxamer 188 in arresting calcein leakage from thermally
      damaged isolated skeletal muscle cells.

PMID- 7516631
TI  - Specificity of bronchoalveolar lavage for the diagnosis of fat embolism syndrome.
AB  - The diagnosis of fat embolism syndrome (FES) is relatively difficult because
      simple, quantitative criteria have been lacking. The results of a recent study,
      however, suggest that the diagnosis of FES can be made if more than 5 per cent of
      the cells in fluid obtained by bronchoalveolar lavage are lipid-laden. Our study
      was designed to assess the specificity of this lipid staining test of
      bronchoalveolar cells for diagnosing FES in a series of patients coming to the
      pulmonology clinic. Thirty-four consecutive patients with suspected pulmonary
      diseases, but not FES, underwent routine bronchoscopy. Bronchoalveolar fluid was
      applied to slides, fixed with formalin, and stained with oil red 0. Three hundred
      consecutive cells of each specimen were observed for red-staining droplets. More
      than 5 per cent of bronchoalveolar lavage cells stained for lipids in 25 of the
      34 subjects. The calculated specificity, assuming a negative finding is defined
      as < or = 5 per cent lipid-laden cells in the sample, was 26.5 per cent. We
      conclude that staining of bronchoalveolar lavage cells for lipids is not a
      specific test for FES.

PMID- 7516630
TI  - Hypertonic saline/dextran improves septic myocardial performance.
AB  - An isolated perfused heart preparation was used to determine the effects of
      hypertonic saline dextran on contractile performance in both control and septic
      animals. Myocardial performance was assessed by developed pressure (DP), maximal
      rate of tension development (dp/dtmax) and relaxation (-dp/dt). Coronary flow
      rate was measured and myocardial oxygen consumption (MVO2) determined in the
      septic preparations. The hypertonic perfusate had negligible effects on
      contraction and relaxation in the control group. In the septic group, perfusion
      with the hypertonic solution improved myocardial contractility to 150 per cent of
      baseline DP and +dp/dt and 134 per cent of baseline -dp/dt. These improvements in
      myocardial performance were unrelated to changes in coronary flow or MVO2.

PMID- 7516635
TI  - Towards engineering pathways for the synthesis of analgesics and antitussives.

PMID- 7516634
TI  - Bleomycin biosynthesis: structure of the resistance genes of the producer
      organism.

PMID- 7516632
TI  - Autoantibodies to band 3 during aging and disease and aging interventions.
AB  - An aging antigen, senescent cell antigen, resides on the 911-amino acid membrane
      protein band 3. It marks cells for removal by initiating specific IgG
      autoantibody binding. Band 3 is a ubiquitous membrane transport protein found in
      the plasma membrane of diverse cell types and tissues, and in nuclear,
      mitochondrial, and golgi membranes. Band 3 in tissues such as brain performs the
      same functions as it does in red cells. Senescent cell antigen is generated on
      brain menbranes. Oxidation is a mechanism for generating senescent cell antigen.
      Neither cross-linking nor hemoglobin appears to play a role in generating
      senescent cell antigen. Although storage is the only in vitro model that mimics
      cellular aging in situ, we have discovered three alterations/mutations of band 3
      that permit insight into aging in situ. One mutation with an addition to band 3
      has normal or decelerated red cell aging. In contrast, another band 3 alteration
      with a suspected deletion or substitution that renders band 3 more susceptible to
      proteolysis, shows accelerated aging. The third alteration, which is also more
      susceptible to proteolysis, is associated with neurologic defects. Peptide
      technology was used to map the aging antigenic sites and anion transport sites on
      band 3 using a competitive inhibition assay and immunoblotting with IgG directed
      against the aging antigen on old cells. Results indicate that: a) aging antigenic
      sites reside on human band 3 residues 538-554, and 812-830; b) a putative ankyrin
      binding region peptide is not involved in senescent cell antigen activity; and
      (c) carbohydrate moieties are not required for the antigenicity or recognition of
      senescent cell antigen since synthetic peptides alone abolish binding of
      senescent cell IgG to erythrocytes. Peptide residues 588-594 (a 7-amino acid
      peptide), 822-839, and 869-883 were the most active inhibitors of anion transport
      (p < or = 0.001 compared to control without peptide). Localization of the active
      antigenic and transport sites on band 3 molecule facilitates definition of the
      molecular changes occurring during aging that initiate molecular as well as
      cellular degeneration. The role of senescent cell antigen and band 3 in brain
      aging and Alzheimer's disease is discussed. Antibodies to one component of
      synthetic senescent cell antigen distinguish between Alzheimer's and normal
      tissue.

PMID- 7516636
TI  - Simple mucins (T, sialosyl-T, Tn and sialosyl-Tn) are not diagnostic for
      malignant breast lesions.
AB  - Immunohistochemical study of the distribution of carbohydrate core-structures on
      O-linked glycoproteins (T, sialosyl-T, Tn and sialosyl-Tn) was performed using
      specific monoclonal antibodies on 148 primary breast lesions, including 10 normal
      breast tissues, 16 benign lesions and 122 invasive carcinomas (79 localized and
      43 metastatic lesions). T antigen, not observed in normal breast tissue, was
      present in 31% of the benign lesions and in some cases of morphologically normal
      epithelium adjacent to tumor cells, compatible with altered glycosylation being
      an early event. Sialosyl-T (s-T) antigen was present in all cases of normal
      epithelium and in 81% of the benign lesions. Both Tn and sialosyl-Tn (s-Tn)
      antigen were present in normal breast lesions. Both Tn and sialosyl-Tn (s-Tn)
      antigen were present in normal breast tissue (30%) and benign lesions (31% and
      19%). In the malignant lesions, 20% were positive for T antigen, 82% for s-T
      antigen, 66% for Tn antigen and 22% for s-Tn antigen. The staining pattern was
      nearly identical for carcinomas with and without lymph node metastases. In
      conclusion, immunostaining for simple mucins does not permit a clear distinction
      between benign and malignant breast lesions.

PMID- 7516638
TI  - Prognostic value of cytokeratins and carcinoembryonic antigen expression in
      primary surgically treated cervical cancer.
AB  - In a previous study we have shown the prognostic value of expression of
      cytokeratins and carcinoembryonic antigen (CEA) in cervical cancer FIGO stage
      III. The present study was performed to evaluate the prognostic value of
      cytokeratins and CEA in patients with cervical primary cancer stage IB to IIB,
      surgically treated by radical hysterectomy and lymphadenectomy. Seventy-six
      patients were included in the study. By application of immunohistochemistry we
      found AE1/AE3 (cytokeratins) expression in 27 (35.5%) cases and CEA expression in
      56 (73.7%) cases. Multivariate analysis for the end points of relapse-free
      survival and overall survival showed that neither AE1/AE3 expression nor CEA
      expression had a prognostic value in the studied population. In contrast to
      patients with primary irradiated cervical carcinoma FIGO stage III, patients with
      primary surgically treated tumors stage IB to IIB showed no significant
      prognostic value of cytokeratin or CEA expression of the tumor.

PMID- 7516640
TI  - The increase of CD5LOW+NK cells in patients with multiple myeloma and
      plasmacytoma.
AB  - CD5 antigen is present on all normal alpha beta T cells and some B cells. Human
      NK cells do not usually express CD5 antigen, but we found a novel subset of
      CD5LOW (low density of CD5) positive (CD5LOW+) natural killer cells (NK cells) in
      patients with multiple myeloma (MM) and plasmacytoma. To detect CD5LOW+NK cells,
      we examined the lymphocytes of 23 patients with MM and plasmacytoma by flow
      cytometry. Five out of 23 patients had CD5LOW+NK populations. These patients had
      many more NK cells than the other patients in the peripheral blood and bone
      marrow. The CD5LOW+NK cells had CD2, low density of CD8, CD16 and CD56, but no
      CD3, CD19, or CD20. Most of the CD5LOW+NK cells had HLA-DR, unlike the CD5-NK
      cells. Sorted CD5LOW+CD16+ populations were large granular lymphocytes (LGL). The
      CD5LOW+NK cells had some lytic activity on K562 cells in a 4-hour 51Cr release
      assay. Our results indicate that there is a novel subset of NK cells in some
      patients with MM and plasmacytoma and that CD5LOW+NK cells may be associated with
      NK cell activation.

PMID- 7516637
TI  - Cisplatin, 5-fluorouracil and alpha interferon in non small cell lung carcinoma:
      a toxicity study.
AB  - Data are presented on the general and hematological toxicity of a cisplatin
      (DDP), 5-fluorouracil (5-FU) and alpha interferon (IFN-alpha) association in
      patients with stage III B or IV non small cell lung cancer (NSCLC). Twenty
      patients received DDP (100 mg/mq i.v., day 1) and 5-FU (750 mg/mq/day i.v.
      continuous infusion, days 1 to 4). In ten of these patients IFN-alpha (3 MU s.c.,
      three times weekly, days 1 to 21) was added. General and hematological toxicity
      was of a similar degree in both groups. Recombinant granulocyte colony
      stimulating factor (G-CSF; 5 micrograms/kg b.w. s.c. days 7 to 18) induced a
      sharp increase in peripheral blood GM-CFU level in patients receiving DDP and 5
      FU but not in DDP, 5-FU, IFN-alpha treated patients. The results appear to
      indicate that IFN-alpha modulation of a DDP, 5-FU combination induces an
      acceptable degree of toxicity.

PMID- 7516641
TI  - A prospective randomized trial of thymopentin versus granulocyte--colony
      stimulating factor with or without thymopentin in the prevention of febrile
      episodes in cancer patients undergoing highly cytotoxic chemotherapy.
AB  - One hundred patients with advanced carcinoma undergoing highly cytotoxic
      chemotherapy were enrolled in a prospective randomized trial comparing
      subcutaneous G-CSF, thymopentin, a combination of the two, and placebo as
      preventive treatment of febrile leukopenia. Data from this study show that G-CSF
      was very active in reducing the incidence of chemotherapy-related fever and
      leukopenia as compared to placebo (22% versus 64%). This difference was
      statistically highly significant (P < 0.001). Thymopentin was associated with a
      reduction in febrile episodes as compared to placebo (52% versus 64%), but this
      difference did not reach statistical significance. Moreover, the addition of
      thymopentin to G-CSF did not result in a statistically significant improvement of
      results obtained with G-CSF alone. Similar results were achieved for fungal
      infections. Tolerance to thymopentin was excellent, while less than 9% of
      patients on G-CSF treatment complained of mild nausea and generalized bone pain.

PMID- 7516642
TI  - Intracavitary treatment of malignant pleural and peritoneal effusions in cancer
      patients.
AB  - Authors present a review of the intracavitary treatment of malignant effusions in
      cancer patients, experience with tetracycline, mechloretamine, quinacrine, radio
      isotopes, interferon beta and interferon alpha are reviewed. Personal experience
      with interferon alpha is reported.

PMID- 7516643
TI  - Modulation of ion channels by protein phosphorylation and dephosphorylation.
AB  - Modulation of the properties of membrane ion channels is of fundamental
      importance for the regulation of neuronal electrical activity and of higher
      neural functions. Among the many potential molecular mechanisms for modulating
      the activity of membrane proteins such as ion channels, protein phosphorylation
      has been chosen by cells to play a particularly prominent part. This is not
      surprising given the central role of protein phosphorylation in a wide variety of
      cellular, metabolic, and signaling processes (26, 27, 48). As summarized here,
      regulation by phosphorylation is not restricted to one or another class of ion
      channel; rather, many, and perhaps all, ion channels are subject to modulation by
      phosphorylation. Similarly, a number of different protein kinase signaling
      pathways can participate in the regulation of ion channel properties, and it is
      not unusual to find that a particular channel is modulated by several different
      protein kinases, each influencing channel activity in a unique way. Finally, the
      biophysical mechanisms of modulation also exhibit a striking diversity that
      ranges from changes in desensitization rates to shifts in the voltage dependence
      and kinetics of channel activation and inactivation. The convergence of channel
      molecular biology with patch-clamp technology has been spectacularly productive,
      even allowing the identification of particular amino acid residues in ion channel
      proteins that participate in specific modulatory changes in channel biophysical
      properties. This task is far from complete, and no doubt there remain surprises
      in store for us, but nevertheless it is appropriate to ask where we go from here.
      One important direction will be to relate functional modulation, produced by
      phosphorylation, to changes in the three-dimensional structure of the ion channel
      protein. Unfortunately, structural studies of membrane proteins are extremely
      difficult, and to date there is no high resolution structure available for any
      ion channel protein. A complementary strategy that is more feasible with current
      technology is to investigate the ways in which channel modulation contributes to
      the regulation of cellular physiology. Novel computational approaches are being
      brought to bear on this complex issue, and their combination with channel
      molecular biology and biophysics should significantly advance our understanding
      of molecular mechanisms of neuronal plasticity.

PMID- 7516639
TI  - Two cases of "multicystic peritoneal mesothelioma": description and critical
      review of the literature.
AB  - Two cases of multicystic peritoneal mesothelioma (MPM) are reported.
      Ultrastructural and immunohistochemical techniques confirmed the mesothelial
      nature of the lesion. The biologic and clinical behaviour, pathogenesis and
      differential diagnoses of this rare pathology are discussed. Although regarded as
      a neoplasm, many analogies seem to link MPM to fibromatoses and other non
      neoplastic lesions, suggesting a reactive hyperplastic process. The relationships
      between mesothelium and the secondary Mullerian system, to date not fully
      investigated, are stressed and a classification of the coelomatic reactive and
      neoplastic processes, both metaplastic (mullerian metaplasia) and non
      metaplastic, is suggested.

PMID- 7516644
TI  - Vesicle targeting and ion secretion in epithelial cells: implications for cystic
      fibrosis.
AB  - The cellular mechanisms that lead to the asymmetric distribution of ion transport
      proteins and the capacity for cAMP-stimulated Cl- secretion at the cell and
      organelle level are beginning to emerge. Testable models exist for many of the
      steps involved in the generation and maintenance of epithelial plasma membrane
      protein asymmetry. The challenge today for the cellular physiologist is to
      integrate these findings into an understanding of epithelial targeting phenomena
      and the manner in which these mechanisms are altered by disease states.

PMID- 7516645
TI  - Ryanodine receptor/Ca2+ release channels and their regulation by endogenous
      effectors.

PMID- 7516647
TI  - Use of expandable wire stents for malignant airway obstruction.
AB  - The symptoms of progressive dyspnea and stridor in the setting of malignant
      airway obstruction are severe and distressing. Conservative nebulizer and oxygen
      therapy offer little relief, and conventional stenting with T tubes requires a
      tracheostomy. In this article, we describe our experience with stenting in the
      treatment of malignant mediastinal disease using the Gianturco expanding metal
      wire stents. The technique of placement is simple and the procedure was
      successful in all 21 cases. Relief of stridor was immediate and the dyspnea
      usually abated. These benefits continued through the mean survival period after
      stenting of 134 days (range, 2 to 799 days). The patients required only brief
      hospitalization (2.83 days) before returning home or to the referring
      institution. It appears that expandable wire stents may offer a simple yet
      effective intervention in the palliative treatment of mediastinal malignancy.

PMID- 7516648
TI  - [Aprotinin in cardiac surgery in patients with platelet anti-aggregant
      treatment].
AB  - A large number of coronary patients referred for coronary bypass surgery receive
      platelet anti-aggregant therapy which has the disadvantage of increasing per and
      postoperative haemorrhage. The aim of this study was to assess the effects of
      aprotinin in 60 patients under platelet antiaggregant therapy (aspirin 250
      mg/day) for over 30 days before surgery for coronary bypass grafting. The
      clinical (age, weight, diagnosis, bypass time, number of grafts) and biological
      features (preoperative haemoglobin concentration, platelet count and fibrinogen
      levels) were identical in a group treated by aprotinin (Group A, n = 30) and a
      control group (Group B, n = 30). The aprotinin treatment protocol was an
      intravenous injection of 2 million KIU (kallikrein inhibitory units) before
      starting the cardiopulmonary bypass and 2 million KIU in the filling liquid of
      the bypass circuit. A significant reduction in blood loss was observed in Group A
      with respect to Group B (370 +/- 154 ml versus 651 +/- 323 ml at day 1, p <
      0.01). The haemoglobin concentration was higher in Group A than in Group B (11.9
      +/- 1.6 g/100 ml versus 10.3 +/- 1.4 g/100 ml, p < 0.001) and fewer patients
      required blood transfusion (Group A: 16% versus Group B: 43%, p = 0.04). In
      conclusion, high doses of aprotinin given to patients on aspirin therapy
      undergoing coronary bypass surgery, significantly reduce postoperative blood loss
      and the number of patients transfused.

PMID- 7516646
TI  - Angiogenesis: an indicator of metastasis in non-small cell lung cancer invading
      the thoracic inlet.
AB  - We have attempted to identify a biologic rationale for the local aggressiveness
      and late treatment failure of resected non-small cell lung cancer involving the
      thoracic inlet. Tumor specimens from 28 patients who underwent a new
      transcervical approach were analyzed for the expression of tumor proliferative
      activity, suppressor-gene p53, intratumoral and peritumoral blood vessel invasion
      by tumor cells, the presence and degree of angiogenesis (induction of new
      capillaries and venules), and other biologic variables. Eighty-nine percent of
      the neoplasms were moderately or poorly differentiated, 89% expressed either an
      intermediate or high proliferative activity, 39% showed p53 aberrations, 71%
      exhibited induction of angiogenesis, and 39% had tumors that were positive for
      blood vessel invasion. With a median follow-up time of 3.5 years (range, 8 to
      145+ months), the overall projected 5-year survival was 29% and the median
      disease-free interval was 23 months. Results of univariate and multivariate
      analysis of survival and the disease-free interval identified the degree of
      angiogenesis (density less than 1 versus more than 1 and number of neovessels
      less than 6 versus more than 6) as the only independent and significant
      predictors of the disease-free interval. Patients whose tumor showed a density of
      angiogenesis of 1 or greater and a number of neovessels of 6 or greater faced a
      significantly (p = 0.0001) higher relative risk of suffering systemic recurrence
      of their primary tumor than did their low-risk counterparts. Results demonstrate
      that angiogenesis significantly correlates with late treatment failure
      (metastasis), and this is acquired at a critical density and number of vessels.

PMID- 7516649
TI  - [Heart rate and rhythm during flight in civil pilots undergoing aerobatics. A
      Holter study].
AB  - Variations in heart rate and arrhythmic risk were analysed during aerobatic
      manoeuvres carried out by 23 amateur pilots, affiliated to an air club or in the
      French national team, during training or competitive flight, by 43 Holter 2
      channel continuous electrocardiographic recordings. The maximum, mean and minimum
      heart rates were raised before the flight started and were observed to attain or
      even exceed the age-predicted maximum heart rate during the manoeuvres. These
      values were independent of age, the pilot's experience, the acceleration forces,
      the duration of the flight or the aerobatic figures performed. On the other hand,
      the heart rate was much higher during competition than during training and pilot
      experience modified its variations, indicating that psychological stress played a
      major role in inducing the tachycardia. Aerobatic flying was only mildly
      arrhythmogenic, inducing some isolated extrasystoles and one short run of
      asymptomatic supraventricular tachycardia. Holter recording is a simple and
      economic method of monitoring aerobatic pilots and could help to improve training
      methods and our understanding of the physiological changes observed during
      flight.

PMID- 7516650
TI  - Interferon inhibitors and/or inactivators in sera from patients with neoplasias.
AB  - Measurements of interferons, their inhibitors and/or inactivators and tumor
      necrosis factor-like activities in sera from patients with neoplasias were
      performed. Interferon activity could not be detected in 96% of the sera samples
      examined. In contrast, both interferon inhibitors and/or inactivators and tumor
      necrosis factor-like activities were found in a high proportion (25-100%) of sera
      from cancer patients but not in sera from normal individuals.

PMID- 7516652
TI  - Prostatic cancer.

PMID- 7516651
TI  - Interferon caused alterations of human cell response to bleomycin in vitro.
AB  - HeLa cells were exposed to recombinant interferon-alpha (rIFN-alpha) in
      combination with bleomycin (BLM) concentrations known to exert single as well as
      double-strand breakages of cellular DNA. rIFN-alpha is added before or/and after
      cell treatment with BLM. The sensitivity of HeLa cells to BLM or/and rIFN was
      assessed from the number and the size of cell colonies formed. rIFN-alpha alone
      at concentrations of 250 IU/ml had no effect on the development of HeLa cell
      colonies, in combination with BLM, rIFN-alpha increased the already marked
      inhibition of HeLa cell colony formation caused by 1 microgram/ml BLM. At BLM
      concentrations of 5 and 10 micrograms/ml the inhibition of HeLa cell colony
      formation was almost complete and no overlapped effect of BLM and rIFN-alpha can
      be distinguished. However, rIFN-alpha afforded protection of HeLa cells colony
      formation when it was added before BLM treatment or it was present continuously
      thereafter.

PMID- 7516653
TI  - Histological comparison of the third interdigital nerve in patients with Morton's
      metatarsalgia and control patients.
AB  - This study compares the histology of the plantar-digital nerve supplying the
      third web space in asymptomatic patients with those who have clinically diagnosed
      Morton's metatarsalgia. Despite several studies concentrating on the histological
      changes in the interdigital nerve, the relevance of these changes is a matter of
      contention while the exact pathological process responsible for the symptoms has
      not been determined. The histological findings in control patients were identical
      to Morton's patients with the exception of demyelination, which was more common
      in the Morton's group. This suggests that the characteristic nodule and fibrotic
      changes seen in the interdigital nerves of patients with Morton's neuroma cannot
      account for the symptoms and that the changes seen in the neurovascular bundle
      are degenerative in origin and are found in asymptomatic patients.

PMID- 7516654
TI  - Decreased arachidonic acid metabolism in human platelets by autologous
      neutrophils: possible role of cell adhesion.
AB  - The amount of the 12-lipoxygenase and cyclo-oxygenase products, 12(S)-hydroxy
      (Z,Z,E,Z)-5,8,10,14-eicosatetraenoic acid (12-HETE) and 12(S)-hydroxy-(E,E,Z)
      5,8,10-heptadecatrienoic acid (HHT), in human platelets stimulated by thrombin
      (0.1 and 2.5 units/ml), was studied in the presence of autologous neutrophils. A
      decreased formation of both products was induced by unstimulated neutrophils or
      neutrophils challenged with N-formylmethionyl- leucyl-phenylalanine (0.1 microM)
      or Ca2+ ionophore A23187 (0.15 microM). The effect of neutrophils was observed
      only in the presence of Ca2+. 12-HETE and HHT were also produced in platelets
      stimulated with thrombin in the absence of Ca2+ and/or Mg2+, but their level was
      not altered by neutrophils. 12(S),20-Dihydroxy-(Z,Z,E,Z)-5,8,10,14
      eicosatetraenoic acid (12,20-DHETE), the cytochrome P-450 product from 12-HETE in
      neutrophils, was hardly detected, and its level did not compensate for the
      decrease in 12-HETE observed after platelet and neutrophil co-incubation.
      5(S),12(S)-Dihydroxy-(E,Z,E,Z)- 6,8,10,14-eicosatetraenoic acid (5(S),12(S)
      DHETE), the 5-lipoxygenase product of 12-HETE in neutrophils, was never
      detectable. In addition, the inhibition of 12-HETE and HHT formations appeared
      not to be due to degradation or thrombin uptake by neutrophils, nor was the
      decrease observed when the two cell populations were physically separated. A
      monoclonal antibody against the human platelet glycoprotein GMP140 (CD62),
      mediating Ca(2+)-dependent platelet-neutrophil adhesion, mimicked the inhibitory
      effect of neutrophils in a dose-dependent fashion. Furthermore, the 12-HETE and
      HHT productions were not affected when platelets were stimulated in the presence
      of neutrophils previously incubated with sialidase, which removes the sialic acid
      from a sialyl Lewis(x) structure assumed to be the neutrophil receptor for
      platelet GMP140. We conclude that the decrease in thrombin-stimulated 12-HETE and
      HHT formation observed when platelets were co-incubated with autologous
      neutrophils might be the consequence of platelet-neutrophil adherence, presumably
      through platelet GMP140.

PMID- 7516655
TI  - Agonist regulation of cellular Gs alpha-subunit levels in neuroblastoma x glioma
      hybrid NG108-15 cells transfected to express different levels of the human beta 2
      adrenoceptor.
AB  - Neuroblastoma x glioma hybrid NG108-15 cells endogenously express at least three
      receptors which activate adenylate cyclase via the intermediacy of the
      stimulatory G-protein, Gs. Sustained exposure of the cells to agonists at the IP
      prostanoid receptor results in a substantial decrease in cellular levels of the
      alpha-subunit of Gs (Gs alpha) [McKenzie and Milligan (1990) J. Biol. Chem. 265,
      17084-17093; Adie, Mullaney, McKenzie and Milligan (1992) Biochem J. 285, 529
      536]. By contrast, equivalent treatments of the cells with agonists at either the
      A2 adenosine receptor or the secretin receptor have no measurable effect on
      cellular amounts of Gs alpha. To examine whether this is a feature specific to
      the IP prostanoid receptor or is related to the level of expression of the
      individual receptors, NG108-15 cells were transfected with a construct containing
      a human beta 2-adrenoceptor cDNA under the control of the beta-actin promoter.
      Two clones of these cells were examined in detail, beta N22, which expressed some
      4000 fmol/mg of membrane protein, and clone beta N17, which expressed approx. 300
      fmol/mg of membrane protein of the receptor. Exposure of beta N22 cells to the
      beta-adrenergic agonist isoprenaline resulted maximally in some 55% decrease in
      membrane-associated levels of Gs alpha, without effect on membrane levels of Gi2
      alpha, Gi3 alpha, G(o) alpha or Gq alpha/G11 alpha. Dose-response curves to
      isoprenaline in beta N22 cells indicated that half-maximal down-regulation of Gs
      alpha was produced by approx. 1 nM agonist. Equivalent exposure of beta N17 cells
      to isoprenaline did not significantly modify levels of any of the G-protein alpha
      subunits, including Gs alpha. In beta N22 cells the IP prostanoid receptor was
      expressed at similar levels to those in wild-type NG108-15 cells, and treatment
      with iloprost resulted in a similar down-regulation of cellular Gs alpha levels.
      Iloprost was also effective in causing down-regulation of Gs alpha levels in
      clone beta N17. Concurrent addition of both isoprenaline and iloprost to clone
      beta N22 resulted in less than additive down-regulation of Gs alpha. These
      results demonstrate that the phenomenon of agonist-induced specific G-protein
      down-regulation is determined by the levels of expression of the receptor.

PMID- 7516657
TI  - Enhancement of antineoplastic activity of 5-fluorouracil in mice bearing colon 38
      tumor by (6R)5,10-dideazatetrahydrofolic acid.
AB  - (6R)5,10-Dideazatetrahydrofolic acid (DDATHF, Lometrexol), a potent antitumor
      drug in vivo and in vitro, is an inhibitor of the two folate-dependent enzymes in
      the de novo purine biosynthesis pathway: glycinamide ribonucleotide (GAR) and
      amino imidazole carboxamide (AICAR) transformylases. A single dose of DDATHF (50
      mg/kg, i.p.) in C57/BL6 mice caused a prolonged depletion of purine nucleotides
      (ATP and GTP) in colon 38 tumor and only a temporary effect in liver. GAR
      transformylase activity was higher in colon 38 tumor than in liver, but a kinetic
      analysis on the purified enzyme showed no differences in Ki values for DDATHF or
      Km values for the folate substrate. As a consequence of de novo purine synthesis
      inhibition, there was a 2- to 3-fold elevation of 5-phosphoribosyl-1
      pyrophosphate pools in colon 38 tumor between 4 and 12 hr after DDATHF
      administration. When DDATHF (50 mg/kg) was administered 4 or 8 hr prior to 5
      fluorouracil (5-FU; 85 mg/kg, i.p., weekly), these biochemical effects
      significantly increased the antitumor activity of 5-FU, with a modest increase in
      toxicity. Lower doses of DDATHF (25 and 37.5 mg/kg) when combined with 5-FU also
      resulted in an improved antitumor activity without additional toxicity. The two
      different schedules of administration for DDATHF, 4 and 8 hr prior to 5-FU,
      showed no differences in antitumor activity or toxicity.

PMID- 7516656
TI  - The role of Glu-60 in the specificity of the recombinant ribonuclease from
      Bacillus amyloliquefaciens (barnase) towards dinucleotides, poly(A) and RNA.
AB  - A computer model of the complex between G2'p5'G and barnase, the recombinant
      ribonuclease of Bacillus amyloliquefaciens, was constructed, based on the known
      structure of the complex RNAase T1.G2'p5'G. This model suggests that the
      conserved residue Glu-60 plays an important role in the specificity of barnase
      for guanosine. A barnase mutant was therefore made in which Glu-60 was replaced
      by Gln. This mutation increases the Km for the dinucleotides GpC and GpA, by a
      factor of 10, but does not change the kcat. For ApA, the kcat/Km decreases by a
      similar factor, but the individual parameters could not be determined. The
      mutation, however, has no influence on the kcat and the Km of barnase action
      towards RNA and poly(A). This demonstrates that the interactions between the
      substrate and the residue at position 60 must be different in the case of ApA and
      poly(A). For RNA, this conclusion is also likely, but not absolutely certain,
      because barnase/RNA might be a Briggs-Haldane type enzyme/substrate pair.
      Therefore, if the effect of the mutation were limited to an increase of the
      dissociation rate constant of the substrate (k-1), this would not be evident in
      Km or kcat/Km. In view of the clear cut situation with poly(A), the pH profile
      for and the effect of salt concentration on the kinetic parameters of the mutant
      barnase were studied for this substrate. The influence of salt on the Km can be
      interpreted via the linked function concept and shows a cooperative dissociation
      of 7-10 counterions upon poly(A) binding. The binding of the substrate is
      strongly reduced at high pH, and the pKa involved decreases strongly at high salt
      concentrations. Poly(A) and RNA show a pH dependency of their absorbance
      spectrum, indicating a pH-dependent change of base stacking, which may influence
      the catalytic parameters.

PMID- 7516658
TI  - Kinetic studies with the non-nucleoside human immunodeficiency virus type-1
      reverse transcriptase inhibitor U-90152E.
AB  - The bisheteroarylpiperazine U-90152E is a potent inhibitor of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and possesses
      excellent anti-HIV activity in HIV-1-infected lymphocytes grown in tissue
      culture. The compound inhibits both the RNA- and DNA-directed DNA polymerase
      functions of HIV-1 RT. Kinetic studies were carried out to elucidate the
      mechanism of RT inhibition by U-90152E. Michaelis-Menten kinetics, which are
      based on the establishment of a rapid equilibrium between the enzyme and its
      substrates, proved inadequate for the analysis of the experimental data. The data
      were thus analyzed using Briggs-Haldane kinetics, assuming that the reaction is
      ordered in that the template:primer binds to the enzyme first, followed by the
      addition of dNTP and that the polymerase is a processive enzyme. Based on these
      assumptions, a velocity equation was derived, which allows the calculation of all
      the essential forward and backward rate constants for the reactions occurring
      between the enzyme, its substrates and the inhibitor. The results obtained
      indicate that U-90152E acts exclusively as a mixed inhibitor with respect to the
      template: primer and dNTP binding sites for both the RNA- and DNA-directed DNA
      polymerase domains of the enzyme. The inhibitor shows a significantly higher
      binding affinity for the enzyme-substrate complexes than for the free enzyme and
      consequently does not directly impair the functions of the substrate binding
      sites. Therefore, U-90152E appears to impair an event occurring after the
      formation of the enzyme-substrate complexes, which involves either inhibition of
      the phosphoester bond formation or translocation of the enzyme relative to its
      template:primer following the formation of the ester bond.

PMID- 7516659
TI  - Inhibition of nitric oxide synthase by antineoplastic anthracyclines.
AB  - Nitric oxide synthase, the enzyme responsible for the synthesis of nitric oxide
      and citrulline from arginine, was potently inhibited by the anthracycline
      antibiotics doxorubicin (Ki = 24 microM) and aclarubicin (Ki = 50 microM). These
      drugs were non-competitive inhibitors with respect to arginine. This action on
      nitric oxide synthase may explain some of the cardiovascular and cytotoxic
      actions of these chemotherapeutic drugs.

PMID- 7516661
TI  - De novo methylation of an MHC class I transgene following transformation with
      human adenoviruses is not correlated with its altered expression.
AB  - The biological importance of class I histocompatibility antigens in a large
      variety of immune mechanisms is widely recognized, and their role in tumor
      rejection has been proven in several experimental tumor systems. Reduced
      expression of class I antigens, which is correlated with enhanced tumorigenicity,
      was shown in these systems to be mainly the result of transcriptional down
      regulation. Mouse embryonal fibroblasts expressing H-2 antigens and the product
      of a miniature swine class I transgene, transformed by adenovirus 12, exhibit low
      levels of all class I antigens on the cell surface. Half of the cell lines
      demonstrate a suppressed level of class I mRNAs. Cell lines derived from
      transformation with the early region of adenovirus 5 express a high level of
      class I antigens. DNAs from adenovirus-transformed cells are extensively
      hypermethylated both in the 5' and the coding regions of the transgene compared
      to DNAs from immortalized cell lines and primary embryonal fibroblasts.
      Nevertheless, hypermethylation of these sequences is not correlated with mRNA
      level or cell-surface expression of the transgene product. Treatment of the
      transformed cells with high concentration of 5-azacytidine (5 Aza-C) induced
      merely a minor enhancement in the expression of class I mRNAs and class I
      antigens. Thus, this system is a perfect example of where viral transformation is
      associated with induced methylation of a class I gene, but hypermethylation does
      not affect its expression. The role of de novo methylation of genes in this
      system might be associated with transformation, or generation of mutations in CpG
      rich sequences.

PMID- 7516660
TI  - Effect of covalent labeling of dextran-benzenehexacarboxylate on hemoglobin.
AB  - The covalent fixation of benzenehexacarboxylate (BHC) onto dextran was carried
      out according to several reaction schemes. The polyanionic polymers thus
      synthesized were capable of decreasing the oxygen affinity of hemoglobin by
      specifically interacting with the 2,3-diphosphoglycerate (2,3-DPG) binding site
      of the protein. The intensity of this effect was correlated to both the chemical
      structure of the polyanionic polymers and the BHC content in polymer. The
      polyanionic polymer, containing 0.035 mol BHC/g and presenting no cross-linking
      between its polymer chains, possessed the best effector properties. These
      properties were used to direct the covalent fixation of the dextran
      benzenehexacarboxylate onto the phosphate binding site of the protein. The
      resulting hemoglobin was mainly substituted at the same time by one or more
      linked BHC onto both alpha beta dimers in the vicinity of the 2,3-DPG site. Thus,
      the modification of hemoglobin led to an increase in the hydrodynamic volume of
      each dimer sufficient to limit the diffusion of the conjugates through the kidney
      membrane, even if the conjugates had dissociated into alpha beta dimers. Compared
      to that of free hemoglobin, the oxygen affinity of the conjugates was
      significantly decreased. This type of covalent conjugate exhibited general
      properties quite suitable for use as blood substitutes.

PMID- 7516662
TI  - Mapping of antigenic and immunogenic sites of Haemophilus influenzae outer
      membrane protein P6 using synthetic lipopeptides.
AB  - The immune response to the P6 protein of Haemophilus influenzae was characterized
      with 24 synthetic icosapeptides and 45 dodecapeptides conjugated to the immune
      stimulator N-palmitoyl-S-[2,3-(bispalmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-( S)
      serine . The antigenicity of these lipopeptides was investigated by enzyme-linked
      immunosorbent assays with rabbit anti-P6 serum. The epitopes of P6 protein were
      identified and localized within residues 31-46 and 59-70 and in the C-terminal
      part of the P6 protein. Mice were immunized with lipoicosapeptides without using
      additional adjuvants or carriers and the antibody titers were measured with
      isolated P6 protein and lipopeptides in a dot blot assay. Lipopeptides containing
      the sequence pattern QILDAHAA (P6 47-54) and the mouse B cell epitope GEYV (P6 43
      46) induced high titers of anti P6 antibodies. These murine antibodies were able
      to neutralize the intact bacterium Haemophilus influenzae.

PMID- 7516665
TI  - HIV-1 gp41 shares a common immunologic determinant with normal human blood
      lymphocytes and monocytes.

PMID- 7516664
TI  - Signaling mechanisms in thymocyte selection.
AB  - The processes known as positive and negative selection that determine the fate of
      T and B cells depend on finely tuned interactions between the T-cell receptor
      complex, CD4 or CD8 co-receptors, and a peptide-MHC complex. New work indicates
      that the avidity of this interaction is critical in the determination of its
      outcome. The effects of these interactions on developing thymocytes are also a
      function of the unique activation properties with which thymocytes are programmed
      just before they undergo selection.

PMID- 7516666
TI  - Anti-angiogenesis agent DS-4152 is a potent and selective inhibitor of HIV-1
      replication in vitro.
AB  - OBJECTIVE: To determine whether the anti-angiogenesis agent DS-4152 inhibits the
      replication of HIV-1 in vitro. DESIGN: A sulfated polysaccharide-peptidoglycan DS
      4152 has recently been identified as a potent and selective inhibitor of Kaposi's
      sarcoma (KS). Therefore, it is important to evaluate the anti-HIV-1 activity of
      DS-4152 alone and in combination with dideoxynucleosides. METHODS: Activity of DS
      4152 against HIV-1 replication was examined in MT-4, Molt-4, and peripheral blood
      lymphocyte cells. The inhibitory effect of the compound on syncytium-formation
      was determined by cocultivation of Molt-4 cells with Molt-4/IIIB cells.
      Inhibition of virus adsorption to the host cells was measured by a p24 antigen
      capture enzyme-linked immunosorbent assay. RESULTS: DS-4152 showed potent and
      selective inhibition of HIV-1 replication in the cell systems. Its 50% effective
      concentration for HIV-1 (IIIB strain) in MT-4 cells was 0.7 microgram/ml. The
      compound was not cytotoxic at concentrations < or = 100 micrograms/ml. DS-4125
      proved inhibitory to syncytium-formation and virus adsorption. The anti-HIV-1
      activities of zidovudine, dideoxycytidine and dideoxyinosine were not affected by
      the presence of DS-4152. CONCLUSION: DS-4152 has the potential, from these in
      vitro studies, to function as an anti-HIV-1 as well as an anti-angiogenesis
      agent. In order to determine this possibility, consequences of DS-4152 infusion
      on HIV-1 p24 serum levels and CD4+ cell counts over time are being examined in
      ongoing clinical trials in the United States on patients with AIDS-associated KS.

PMID- 7516667
TI  - The wisdom of hindsight.
AB  - This essay is a highly personalized account of some of the important conceptual
      contributions to immunology. I have asked myself, "What were the ideas that
      caught my attention and how and by whom were they presented?" I have learned that
      most of what immunologists have called concepts deal with too small a slice of
      the subject. They are essentially inductive extrapolations from one experiment to
      a possible next step. Historically, these extrapolations extended over too narrow
      a chasm to account for the information available at the time. The result was that
      an extrapolation from one misleading observation could dominate and distort, for
      a significant time, the course of the field. It is also why there has been an
      inverse relationship between the clarity of a theory and its ease of acceptance
      by immunologists. Looking to the past, I have used two areas to illustrate the
      role of conceptualization: the self-nonself discrimination and the origin of the
      humoral repertoire. To illustrate all of this I have chosen as a cast of
      characters the founding fathers of immunology as we know it today. I hope that by
      taking this look into the rear view mirror our efforts will be guided in more
      productive ways. The take-home lesson is that we need to widen our horizon
      constantly to make more general concepts that then render the manipulation of the
      immune system more useful.

PMID- 7516668
TI  - Structure of peptides associated with class I and class II MHC molecules.
AB  - Class I and class II molecules encoded by genes within the major
      histocompatibility complex play a central role in regulation of immune responses
      through their ability to bind and display small peptides derived from foreign
      antigens. Within the last few years, considerable progress has been made in
      understanding the structures of class I and class II MHC molecules, as well as
      the features of the peptides that are their principal ligands. This review
      summarizes this information and describes how it accounts for both the
      specificity and degeneracy of peptide binding. It also considers how the origin
      and structural features of peptides that have been isolated from MHC molecules,
      so-called "naturally processed" peptides, have provided insight into the pathways
      through which the peptides are produced. Finally, the use of new structural
      information and techniques for peptide characterization for the identification of
      peptides that comprise epitopes for individual antigen-specific T cells are
      considered.

PMID- 7516669
TI  - The CD40 antigen and its ligand.
AB  - CD40 is an integral membrane protein found on the surface of B lymphocytes,
      dendritic cells, follicular dendritic cells, hematopoietic progenitor cells,
      epithelial cells, and carcinomas. It is a 45-50 kDa glycoprotein of 277 aa, which
      is a member of the tumor necrosis factor receptor superfamily. The CD40 gene maps
      to human chromosome 20q11-2-q13-2. CD40 binds to a ligand (CD40-L) which is an
      approximately 35 kDa glycoprotein of 261 aa, a member of the tumor necrosis
      factor superfamily. The CD40-L gene maps to human chromosome Xq24. This CD40-L is
      expressed on activated T cells, mostly CD4+ but also some CD8+ as well as
      basophils/mast cells. The CD40-L is defective in the X-linked hyper-IgM syndrome.
      Cross-linking of CD40 with immobilized anti-CD40 or cells expressing CD40-L
      induces B cells to proliferate strongly, and addition of IL-4 or IL-13 allows the
      generation of factor-dependent long-term normal human B cell lines and the
      secretion of IgE following isotype switching. Addition of IL-10 results in very
      high immunoglobulin production with limited cell proliferation. IL-10 induces
      naive B cells to produce IgG3, IgG1, and IgA1, and further addition of TGF beta
      permits the secretion of IgA2. Several evidences suggest that CD40-dependent
      activation of B cells is important for the generation of memory B cells within
      the germinal centers: (i) CD40 activated germinal center B cells cultured in the
      presence of IL-4 acquire a memory B cell phenotype, (ii) CD40 activated B cells
      can undergo isotype switching, (iii) the deficit of CD40-L results in the hyper
      IgM syndrome characterized by lack of germinal centers in secondary lymphoid
      organ follicles and lack of IgG, IgA, and IgE, and (iv) CD40-L positive T cells
      are present in secondary follicles. Thymic epithelial cells, activated monocytes,
      and dendritic cells express CD40 antigen which may be involved in an enhanced
      cytokine production by these cells, allowing an amplification of T cell
      proliferation. Finally, as other members of the tumor necrosis factor receptor
      family have been shown to bind several ligands, it is possible that CD40 may bind
      other ligands that may trigger CD40 on different cell types such as hematopoietic
      cells or epithelial cells.

PMID- 7516671
TI  - Rules for peptide binding to MHC class II molecules.
AB  - CD4+ T lymphocytes recognize peptide fragments of antigens that lie in the
      antigen binding pocket of class II major histocompatibility complex (MHC)
      molecules expressed on antigen-presenting cells. Specificity of T cells is
      determined by structural features of both the MHC molecule and antigenic peptide.
      MHC class II amino acid sequences are highly polymorphic within a population, and
      correlate with individual differences in response to infectious agents, vaccines,
      tumour antigens, and autoantigens. In the last few years several important
      breakthroughs and technological advances have made it possible to clarify the
      role of polymorphism and the molecular events in peptide interaction with major
      histocompatibility complex (MHC) class II proteins. The X-ray structural analysis
      of a MHC class II molecule together with the use of peptide libraries has
      permitted determination of the structural features of the complex between peptide
      antigen fragments and MHC class II proteins. The purpose of this article is to
      review our own studies and those of others on the requirements for peptide-class
      II molecule interaction and discuss possible implications for active immune
      intervention.

PMID- 7516672
TI  - Isoprinosine stimulates granulocyte chemiluminescence and inhibits monocyte
      chemiluminescence in vitro.
AB  - Isoprinosine may delay disease progression in human immunodeficiency virus
      infection, presumably through modulation of lymphocyte function. However, the
      influence of isoprinosine on phagocyte function is largely unknown. This study
      describes the effects of isoprinosine and azidothymidine on phagocyte
      chemiluminescence and migration. Incubation with isoprinosine concentrations of
      250 micrograms/ml and above increased the chemiluminescence of granulocytes.
      Random migration of granulocytes was decreased at isoprinosine concentrations of
      50 micrograms/ml and higher, but chemotaxis was not affected. Azidothymidine
      exerted no effect on the chemiluminescence or migration of granulocytes. For
      monocytes, luminol-enhanced chemiluminescence was reduced at isoprinosine
      concentrations of 250 micrograms/ml and above, whereas migration was not
      affected. These findings suggest that the immunomodulatory properties of
      isoprinosine may extend to phagocytic cells. This may be of significance in the
      treatment of immunodeficiency states.

PMID- 7516663
TI  - Clinical toxicity of the interferons.
AB  - Since their initial description in 1957, the interferons (IFNs) have been
      increasingly used to treat a wide array of diseases. Acute adverse effects, i.e.
      'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and
      gastrointestinal disorders, occur within the first hour or day after starting
      treatment. They are seldom treatment-limiting and are easily manageable. Sub
      acute and chronic effects develop after several days, usually within 2 and 4
      weeks of therapy. The most typical is neurological toxicity, including
      fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may
      seriously impair quality of life and result in treatment discontinuation.
      Seizures have seldom been described. Other infrequent central nervous system
      adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal
      paraesthesias and peripheral neuropathy have been reported. IFN-associated
      autoimmunity is quite rare but a matter of concern. Biological or clinical
      manifestations usually require several months to become apparent. Autoantibodies
      have been shown to develop in most patients but have been inconsistently
      associated with clinical symptoms of systemic lupus erythematosus, rheumatoid
      like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been
      described but are usually reversible. Other infrequent autoimmune reactions
      include diabetes, pemphigus and worsening of multiple sclerosis. Although several
      patients present with a pre-existing autoimmune disorder, no predisposing factor
      has been clearly established. While hypotension and tachycardia are the most
      frequent acute cardiovascular complications, a few additional cases of cardiac
      arrhythmias and myocardial ischaemia have been reported after a short course or
      several weeks of treatment. These latter complications do not appear to be dose
      dependent or age-related. Isolated cases of congestive heart failure have also
      been described. Mild proteinuria has been observed in 15 to 25% of patients, but
      acute renal toxicity is uncommon. A transient rise in serum aminotransferase
      levels is frequently noted during the first stage of therapy, especially in
      patients receiving the highest dosages. Direct hepatotoxicity is extremely rare.
      Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de
      novo induction of autoimmune hepatitis, account for the majority of liver
      diseases. Haematotoxicity is relatively common but mild to moderate, and develops
      gradually during the first weeks of treatment. Neutropenia is the most common
      haematological toxicity, but is usually not dose-limiting and resolves rapidly
      upon drug discontinuation. Myelosuppression, autoimmune and immune allergic
      haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous
      adverse effects comprised nonspecific erythema and hair loss and, less
      frequently, vasculitis, local ulcerations at the site of injection and
      exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516674
TI  - Occupational risk linked to leptospirae in Apulia.

PMID- 7516675
TI  - Community perception and role in prevention of Guinea worm disease.

PMID- 7516670
TI  - Toward a vaccine for AIDS: the emergence of immunobiology-based vaccine
      development.
AB  - Over a decade has passed since the identification of the human immunodeficiency
      virus (HIV) as the causative agent of AIDS. During this time, HIV has been
      extensively characterized, and a variety of vaccine constructs and strategies
      have been explored. For the most part, these have been driven by successes of the
      past with other pathogens, or by novel approaches enabled by technologies of the
      present. With the maturing of our insights into the immunopathology of HIV and
      basic immunological mechanisms, we are presented with unprecedented opportunities
      to rationally develop vaccine approaches strategically designed to counter the
      immunopathology of HIV. As opposed to absolute prevention of infection, the
      primary goal of these strategies may be to limit infection and to assure a
      response to infection that prevents disease and transmission. Thus, such vaccines
      may find utility in both preventive and therapeutic roles. In this paper, we
      present the background and current state of immunobiology-driven vaccine
      development for AIDS.

PMID- 7516676
TI  - A survey of human dracunculiasis in Kitgum District, Uganda.

PMID- 7516677
TI  - [Definition of objectives in surveillance of hospital infections].

PMID- 7516673
TI  - Alteration of immunoreactivity by hydrated autoclaving, microwave treatment, and
      simple heating of paraffin-embedded tissue sections.
AB  - The effects of treatment in a hydrated autoclave (121 degrees C, 2 atm for 20
      min), microwave oven (in water), and simple heating (60 degrees C overnight in
      distilled water or 90 degrees C for 10 min in ZnSO4) on the stainability of 56
      antigens by commercially available antibodies in formalin-fixed paraffin-embedded
      tissue sections were evaluated. The detectability of nuclear antigens,
      glycoprotein, lymphocytic surface markers, and chromogranin A was significantly
      and reproducibly improved by these treatments, whereas the detectability of viral
      antigens and peptide hormones was attenuated or unchanged. This enhancement
      includes not only the distinctiveness of the positive staining, but also the
      number of positive cells, as revealed by comparing serial sections. Among these
      four heating procedures, microwave heating and autoclaving were more effective
      than the others on p53, c-erbB-2, and CA125, whereas simple heating was best for
      smooth-muscle actin (HHF35 and CGA7). Generally the effects of the heating
      procedures for these antigens were consistent among the cases, but the effects on
      GFAP varied with the case. The alterations we observed could significantly
      influence the interpretation of immunohistochemical staining of currently popular
      tumor markers such as p53 in terms of their prevalence (28% vs 64% in gastric
      cancer; 36% vs 82% in metastatic liver cancer) and other diagnostically important
      markers.

PMID- 7516678
TI  - [Cost evaluation in hospital infections of the urinary tract].

PMID- 7516679
TI  - [Echographic activities in a polyclinic: a preliminary study].

PMID- 7516680
TI  - [Coordinated protocol for prevention of HIV and HBV infections in exposed health
      personnel of the Province of Viterbo].

PMID- 7516681
TI  - [Analytical approach to the bacteriological characterization of mineral waters].

PMID- 7516683
TI  - Transcription of circular and noncircular forms of Sry in mouse testes.
AB  - Although its expression in adult testis was immediately apparent, the role for
      Sry (sex determining region, Y) in testicular function remains elusive. We have
      performed transcriptional studies in an effort to elucidate potential roles of
      Sry by studying the time and location of its transcription in mouse testes.
      Northern analyses and more sensitive nuclease protection assays detected
      transcripts in 28-day-old testes and beyond. The highly sensitive technique of
      reverse transcription polymerase chain reaction (RTPCR) could not detect Sry
      expression in 14-day testes when primers for the most conserved portion of the
      gene, the high mobility group (HMG) box, were used, but primers for the circular
      form detected Sry transcription at all postnatal stages studied. The same HMG box
      primers were able to detect expression of Sry in XX, Sxra or Sxrb testes. This
      suggested that Sry is expressed in cells other than germ cells, which was
      confirmed with studies on fractionated cells--RTPCR detected transcription of Sry
      in the highly pure interstitial cell fraction. However, Leydig cells and a Leydig
      cell tumor were negative for Sry expression. We performed in situ studies in an
      attempt to localize the expression of Sry in the testes. Abundant expression of
      an Sry cross-hybridizing transcript was found in spermatogonia, in early
      spermatocytes, and in some interstitial cells with antisense probes to the HMG
      box or a more specific, 3' region, whereas the sense probe gave little or no
      hybridization. It is probable that the circular transcripts, which are seen in
      reverse transcriptase positive (RT+) and RT- reactions by PCR because of the RT
      activity of Taq polymerase, are responsible for the hybridization seen in
      spermatogonia and spermatocytes, whereas linear and circular forms are detected
      later. Thus Sry is expressed in pre- and postmeiotic germ cells and in somatic
      cells of the testes.

PMID- 7516682
TI  - [Characterization and dynamics of microbial facies of natural mineral water].

PMID- 7516684
TI  - Characterization of mouse-hamster-human cross-reacting antioocyte monoclonal
      antibodies produced by intrasplenic immunization of mice with 12 zona-free mouse
      oocytes.
AB  - Several intrasplenic immunizations with batches of approximately 15 or
      approximately 30 zona-free, unfertilized mouse oocytes resulted in 200-300
      hybrids, respectively, among which about 20 positive clones were selected from
      each fusion between splenic plasma cells and SP2/0 myeloma cells. When
      nonimmunized splenic plasma cells were used, only one antibody, showing weak
      immunoreaction, was obtained from approximately 370 hybrids collected from 2
      fusions. From one immunization with a total of 12 zona-free, unfertilized mouse
      oocytes, 15 positive clones were selected for further study. Eleven of these 15
      antibodies reacted with antigens only in unfertilized oocytes but not in
      fertilized, pronuclear stage oocytes. Three antibodies, which recognized antigens
      in paraffin-embedded oocyte sections, did not label growing ovarian oocytes,
      indicating that the antibodies were specific to ovulated, unfertilized oocytes.
      These antibodies did not detect any antigen epitopes in the panel of tissues
      examined. The molecular weight of one antigen, corresponding to a IgM antibody
      that is present both in ooplasma and zona pellucida, was approximately 116 kDa.
      Cross-reactivity to blots of unfertilized zona-free hamster oocytes was
      demonstrated by 6 antibodies and to unfertilized human oocytes by 7 antibodies.
      Three antibodies cross-reacted with both hamster and human oocytes. The study
      indicates that the intrasplenic immunization is an appropriate means of raising
      antibodies against unfertilized, zona-free mouse oocytes and that the method
      applied offers an easy way to select antibodies against human oocytes for
      functional studies.

PMID- 7516685
TI  - Auxiliary subunits of voltage-gated ion channels.

PMID- 7516686
TI  - Cyclic AMP modulates fast axonal transport in Aplysia bag cell neurons by
      increasing the probability of single organelle movement.
AB  - Stimulation of Aplysia bag cell neurons triggers elevation of cAMP and prolonged
      secretion of ELH neuropeptide. Using video-enhanced microscopy to track
      individual organelle movements in bag cell neurons, we find that organelle
      translocation consists of periods of movement interrupted by stationary episodes.
      cAMP elevation leads to a 2- to 3-fold enhancement of the average rate of
      organelle transport in both anterograde and retrograde directions. This effect
      does not result from alteration of the instantaneous velocity of organelle
      transport along microtubules, but rather from an increase in the proportion of
      time individual organelles spend in motion. Biochemical measurements also
      provided evidence that cAMP elevation promotes ELH peptide translocation from the
      somata into axons. Enhanced transport of ELH as a result of these effects may
      contribute to the replenishment of neuropeptide-containing vesicles at release
      sites during prolonged periods of secretion.

PMID- 7516688
TI  - Embryonic expression of myelin genes: evidence for a focal source of
      oligodendrocyte precursors in the ventricular zone of the neural tube.
AB  - 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) is an abundant protein of
      myelinating oligodendrocytes. We report that one of the alternatively spliced CNP
      mRNAs is also expressed in cultured oligodendrocyte progenitor cells. In situ
      hybridization revealed a thin longitudinal column of CNP-positive cells in the
      ventral ventricular zone of the embryonic day 14 rat spinal cord, coincident in
      time and space with cells that express the platelet-derived growth factor alpha
      receptor, another putative marker of the oligodendrocyte lineage. These data
      support the hypothesis that the oligodendrocyte lineage originates at a discrete
      location in the ventral ventricular zone of the embryonic day 14 rat spinal cord.
      We further report that transcripts encoding the myelin proteolipid protein
      (PLP/DM-20) are expressed in an unidentified population of neural progenitors in
      the ventricular zone abutting the floor plate. Our results support the idea that
      the ventricular zone is a mosaic of specialized progenitor cells.

PMID- 7516687
TI  - Angiotensin II inhibits calcium and M current channels in rat sympathetic neurons
      via G proteins.
AB  - We characterized inhibition of N-type Ca2+ and M current K+ channels in rat
      superior cervical ganglion neurons by angiotensin II (angioII) using the patch
      clamp. Of 120 neurons, 97 showed inhibition of ICa (mean 32%), which was slow in
      onset and very slow to reverse under whole-cell recording conditions. This
      inhibition was blocked by the AT1 receptor antagonist losartan, attenuated by
      inclusion of 2 mM GDP-beta-S in the pipette, mostly pertussis toxin insensitive,
      half-sensitive to N-ethylmaleimide, and wholly voltage independent. With 20 mM
      instead of 0.1 mM BAPTA in the pipette, the inhibition was strongly attenuated;
      however, we detected no angioII-induced [Ca2+]i signal using the fluorescent
      indicator indo-1. IBa from cell-attached patches was reduced by bath-applied
      angioII (mean 33%), suggesting use of a diffusible cytoplasmic messenger. M
      currents were inhibited by angioII in 8 of 11 neurons (mean 50%) cultured
      overnight. Hence, a second agonist, angioII, may share the slow, second messenger
      utilizing, pertussis toxin-insensitive signaling pathway used by muscarinic
      agonists.

PMID- 7516690
TI  - Management of unresectable oesophageal cancer: a review of 537 patients.
AB  - We compared and contrasted the potentials of palliation afforded by various
      management methods in a retrospective study of all patients referred to one
      surgical team in a 20-year period. Five hundred thirty-seven patients had
      unresectable oesophageal cancer. There were five treatment groups: group 1
      dilatation plus external radiotherapy (DXR, n = 95), group 2-gastrostomy plus DXR
      (n = 18), group 3-permanent intubation (n = 329), group 4-oesophageal bypass (BP,
      n = 70), and group 5-YAG laser plus brachytherapy (n = 25). Groups 1 and 2 had
      high mortality (4% and 25%) and poor symptom relief, with an average survival of
      2.5 and 3.5 months, respectively. Group 3 had a 20% mortality rate, moderate-to
      good symptom relief and an average survival of 4.2 months. This method was best
      for lower oesophageal cancer. Group 4 had a 22% mortality rate, good symptom
      relief and an average survival of 10.5 months. The BP method was suitable for
      patients with oesophago-airway fistula (OAF) and those with lower oesophageal
      cancer found unresectable at operation. Group 5 had a hospital mortality rate of
      8%, good symptom control and an average survival of 6.2 months. This was suitable
      for all patients (except those with OAF). In palliation of carcinoma of the
      oesophagus the selection of method should be made to suit the characteristic and
      location of the tumour.

PMID- 7516689
TI  - The charybdotoxin receptor of a Shaker K+ channel: peptide and channel residues
      mediating molecular recognition.
AB  - Charybdotoxin (CTX) is a peptide of known structure that inhibits Shaker K+
      channels by a pore-blocking mechanism. Point mutagenesis of all 30 solvent
      exposed residues identified the part of the CTX molecular surface making contact
      with the receptor in the K+ channel. All close-contact residues are clustered in
      a well-defined interaction surface; the shape of this surface implies that the
      outer opening of the Shaker channel conduction pore abruptly widens to a 25 x 35
      A plateau. A mutagenic scan of the S5-S6 linker sequence of the Shaker K+ channel
      identified those channel residues influencing CTX binding affinity. The Shaker
      residues making the strongest contribution to toxin binding are located close to
      the pore-lining sequence, and more distant residues on both sides of this region
      influence CTX binding weakly, probably by an electrostatic mechanism.
      Complementary mutagenesis of both CTX and Shaker suggests that Shaker-F425
      contacts a specific area near T8 and T9 on the CTX molecular surface. This
      contact point constrains Shaker-F425 to be located at a 20 A radial distance from
      the pore axis and 10-15 A above the "floor" of the CTX receptor.

PMID- 7516691
TI  - Modulation of inducible nitric oxide synthase in RINm5F cells.
AB  - The rat insulinoma beta-cell line RINm5F, which shares some homology with
      pancreatic islets, was used to study nitric oxide synthase induction. Nitric
      oxide is involved during beta-cell destruction and possibly in propagation of
      insulin-dependent diabetes mellitus. The cytokine interleukin-1 (IL-1) turned out
      to be the ultimate inducer, whereas tumour necrosis factor-alpha (TNF) and
      unexpectedly the phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate; 10 nM)
      synergistically promoted nitrite accumulation. Besides employing TPA directly,
      the synergistic effect of TNF could be traced back to protein kinase C activation
      since protein kinase C inhibitors (IC50 value for staurosporine: 4 nM) potently
      suppressed nitrite production in the case of IL-1/TNF administration. Further
      experiments using anti-TNF antibodies aimed to an autocrine loop following IL-1
      addition to RINm5F cells, possibly involved in nitrite generation. Moreover, the
      nitric oxide synthase inductive IL-1 signal was antagonized by lipophilic cAMP
      analogues. Our results for nitrite accumulation in RINm5F cells point to
      activating protein kinase C and inhibitory protein kinase A signalling pathways.

PMID- 7516692
TI  - Two new formylated peptides able to activate chemotaxis and respiratory burst
      selectively as tools for studying human neutrophil responses.
AB  - Two new For-Met-Leu-Phe-OH (FMLP) methyl ester analogues, For-Thp-Leu-Ain-OMe
      [Thp1, Ain3] and For-Met-delta zLeu-Phe-OMe [delta zLeu2], able to activate
      selectively chemotaxis and superoxide anion (O2-) release, respectively modulate
      intracellular cyclic AMP (cAMP) levels in different ways. FMLP and [delta zLeu2]
      enhance human neutrophil cAMP levels per se, and this effect is potentiated by Ro
      201724, a non-xanthinic phosphodiesterase (PDE) inhibitor, whereas it is
      counteracted by 3-isobutyl-1-methyl-xanthine (IBMX), a blocker of both
      phosphodiesterase and adenosine receptors. In contrast, [Thp1, Ain3] is
      ineffective. However, no formylated peptides influence cAMP phosphodiesterase
      activity. Neutrophil preincubation with Ro 201724 or IBMX drastically reduces
      chemotaxis and superoxide anion (O2-) production triggered by peptides. Our
      results suggest that: (1) peptide-induced cAMP increase is probably indirect, and
      due mainly to the action on adenosine-sensitive adenylate cyclase; (2) formylated
      peptide, endowed solely with chemotactic activity is unable to increase
      neutrophil cAMP concentration; (3) cAMP elevation may represent a feed-back
      mechanism to inhibit the physiological responses induced by formylated peptides.

PMID- 7516693
TI  - Cholera situation in the Americas.

PMID- 7516694
TI  - Polycythaemia vera. III. Burst-forming units-erythroid (BFU-E) response to stem
      cell factor and c-kit receptor expression.
AB  - We previously demonstrated that highly purified normal human blood burst-forming
      units-erythroid (BFU-E) need the direct action of recombinant human stem cell
      factor (rSCF) in the presence of recombinant human erythropoietin (rEP) and
      recombinant human interleukin-3 (rIL-3) for further development in a serum-free
      medium. To study the response of polycythaemia vera (PV) BFU-E to rSCF, we
      performed dose-response experiments in a serum-free medium using highly purified
      BFU-E from PV patients. A marked increase in the number of PV bursts occurred
      with increasing concentrations of rSCF, compared to normal burst formation, when
      the cells were cultured in the presence of rIL-3 at 1 U/ml. The percentage of
      maximum growth for normal BFU-E was 31 +/- 11% while for PV it was 64 +/- 9% at
      the highest concentration of rSCF (P < 0.01). Without rIL-3, only 11% of maximum
      normal BFU-E growth occurred as the rSCF concentration was increased and the size
      of the colonies was very small, but PV BFU-E still expressed 48% of the maximum
      number of large erythroid bursts (P < 0.001). This demonstrated an enhanced
      sensitivity of PV BFU-E to rSCF, compared to normal BFU-E. The pattern of 59Fe
      incorporation into haem after 8 d of cell culture indicated that PV BFU-E had a
      time course of maturation and a degree of cellular maturity similar to normal BFU
      E. The percentage positivity and intensity of c-kit receptors on PV erythroid
      cells were examined using immunofluorescence flow cytometry. When BFU-E, CFU-E,
      or erythroblasts were incubated with phycoerythrin-conjugated SR-1 anti-c-kit
      receptor monoclonal antibody, 90% of the PV and normal BFU-E displayed c-kit
      receptor at comparable intensities, as well as 80% of the PV and normal CFU-E. A
      distinct loss of c-kit expression occurred with erythroid differentiation beyond
      the CFU-E stage, but at all stages no difference of c-kit receptor expression was
      evident for PV erythroid precursors compared to normal precursors. These results
      indicate that the hypersensitivity to rSCF did not appear to be related to the
      number of c-kit receptors. Since we have previously shown that highly purified PV
      BFU-E are hypersensitive to rIL-3 and rGM-CSF, as well as rEP, it is now evident
      that PV BFU-E are hypersensitive to each of the cytokines that have a prominent
      role in guiding their normal proliferation and differentiation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7516695
TI  - The variation with gestational age of the rheological properties of the blood of
      the new-born.
AB  - A study has been made of the variation of blood viscosity and related factors
      with the gestational age of neonates from 24 weeks to normal term. Viscosity
      increases significantly over this period by 36% at high shear rate (128.5 s-1)
      and 250% at low shear (0.277 s-1). The high shear rate changes can be explained
      largely by the effects of variations in haematocrit and plasma viscosity. At low
      shear rate the same factors are involved together with changes in the plasma
      protein composition, in particular the age-related increase in the concentration
      of the proteins known to induce rouleaux formation. The variation in the degree
      of sialination of fibrinogen with gestational age may also play a part.

PMID- 7516696
TI  - Use of granulocyte colony-stimulating factor (G-CSF) for mobilizing peripheral
      blood stem cells: risk of mobilizing clonal myeloma cells in patients with bone
      marrow infiltration.
AB  - Peripheral blood stem cells have been used for autologous reconstitution of
      haemopoiesis after high dose cytotoxic therapy and produce similar disease
      response rates as autologous bone marrow transplants. Peripheral blood stem cell
      transplants are an especially attractive option for patients in whom marrow
      harvest is not feasible due to bone marrow damage or infiltration. Recombinant
      growth factors mobilize adequate numbers of stem cells from the marrow but their
      effect on tumour cell circulation kinetics is not known. We report a patient with
      multiple myeloma and bone marrow infiltration in whom the use of G-CSF for stem
      cell mobilization led to release of plasma cells into the peripheral circulation
      and contamination of the stem cell harvest.

PMID- 7516698
TI  - The Australian type of nondeletional G gamma-HPFH has a C-->G substitution at
      nucleotide -114 of the G gamma gene.
AB  - Nondeletional hereditary persistence of fetal haemoglobin (HPFH) results in the
      continued production of 2-25% haemoglobin F (Hb F) in the adult who is
      heterozygous for this mutation. This increase is associated with single-base
      mutations in the promoter region of either the G gamma- or A gamma-globin genes.
      Affected positions include -202, -175, -161, -158 and -114 of the G gamma gene,
      and -202, -198, -196, -195, -175, and -117 of the A gamma gene. There is now
      evidence that these mutations produce their effect by changing the binding of
      certain regulatory proteins. We describe a novel C-->G transversion at position 
      114 of the G gamma gene which is associated with the phenotype of G gamma-HPFH.

PMID- 7516697
TI  - Localized, late-onset, high-grade lymphoma following bone marrow transplantation:
      response to combination chemotherapy.
AB  - Non-Hodgkin's lymphoma is the commonest secondary cancer following bone marrow
      transplantation (BMT). We report the case of a 42-year-old man who developed a
      laryngeal high-grade B-cell lymphoma 5 years following a matched T depleted BMT
      for CML. Polymerase chain reaction (PCR) analysis using the microsatellite marker
      Cyp 19 demonstrated the donor origin of involved tissue. Epstein-Barr virus (EBV)
      genomic sequences were identified by PCR. Although EBV related B-cell
      lymphoproliferative disorders (BLPD) post BMT are difficult to treat, there was a
      complete remission in this patient following three courses of chemotherapy (CHOP)
      administered with G-CSF. This case of late-onset BLPD appears clinically distinct
      from the well-defined, aggressive, early post-transplant BLPD.

PMID- 7516699
TI  - Expression of collagen alpha 1(IV), laminin and nidogen genes in the embryonic
      mouse lung: implications for branching morphogenesis.
AB  - The patterns of laminin A, B1, B2, nidogen and collagen alpha 1(IV) gene
      expression in the embryonic mouse lung were determined using in situ
      hybridization histochemistry at a stage when branching morphogenesis is taking
      place. Collagen alpha 1(IV), laminin B1 and B2 genes were expressed throughout
      the mesenchyme and epithelium. Nidogen gene expression was uniform throughout the
      mesenchyme but was not detected in epithelial cells. Laminin A mRNA was localized
      to cells closely associated with a basement membrane at the epithelial
      mesenchymal interface. However, expression of the laminin A gene was limited to
      the mesenchymal cells in bronchial regions and to epithelial cells in distal
      terminal lobules. We propose that the pattern of laminin A gene expression in
      different regions of the developing lung will influence the structure of the
      basement membrane at the epithelial-mesenchymal interface and thus have a role in
      branching morphogenesis.

PMID- 7516700
TI  - Cortical projections to anterior inferior temporal cortex in infant macaque
      monkeys.
AB  - Inferior temporal (IT) cortex is a "high-order" region of extrastriate visual
      cortex important for visual form perception and recognition in adult primates.
      The pattern of cortical afferents from both ipsilateral and contralateral
      hemispheres to anterior IT cortex was determined in infant macaque monkeys 7-18
      weeks of age following injections of wheat-germ agglutinin-HRP. Within the
      ipsilateral hemisphere, the locations and laminar distribution of labeled cells
      were similar to those observed after comparable injections in adult monkeys.
      Specifically, ipsilateral afferents derived from visual areas V4, TEO, anterior
      and posterior IT, and STP, from parahippocampal, perirhinal, and parietal zones,
      and from several anterior zones including lateral and ventral frontal cortex, the
      insula, and cingulate cortex. Within the contralateral hemisphere, we observed
      labeled cells in homotopic regions of IT and in parahippocampal and perirhinal
      areas, as has been reported for adult monkeys. However, we also identified
      additional contralateral regions not previously known to provide input to
      anterior IT, including lateral and ventral frontal cortex, cingulate cortex, and
      STP. Overall, the strongest and most widespread projections from outside the
      temporal lobe were found in the youngest monkey, suggesting that some of these
      projections may represent transient circuitry necessary for the development of
      complex visual response properties in anterior IT.

PMID- 7516701
TI  - The postnatal development of geniculocortical axon arbors in owl monkeys.
AB  - To characterize the postnatal development of geniculocortical axon arbor
      morphology in owl monkeys at a series of ages from birth to adulthood, individual
      arbors were bulk-filled with HRP in brain slice preparations and were
      reconstructed from serial sections. At all ages, cortical layers and sublayers
      were obvious. Presumed M or magnocellular arbors were largely confined to layer
      IV alpha, but they also extended into layer IIIc (IVB of Brodmann, 1909);
      presumed P or parvocellular arbors were almost exclusively confined to layer IV
      beta. Other axons that may reflect feedback projections from MT terminated in
      layer IIIc. Overall, M axon arbors increased in size and complexity from birth to
      adulthood with mean surface-view arbor areas ranging from 0.08 +/- 0.01 mm2 in
      newborns to 0.24 +/- 0.02 mm2 in adults. The developing P arbor areas were, on
      average, as large or larger than adult (newborn = 0.07 +/- 0.01 mm2, adult =
      0.047 +/- 0.01 mm2; n.s.) but the arbors were somewhat less complex. Since the
      brain and area 17 increase in size postnatally, the proportion of area 17
      subserved by each P arbor would decrease in postnatal development. Terminal
      boutons with immature features were evident in both M and P populations at all
      developmental ages. The results indicate that, while both LGN axon types in
      monkeys undergo morphological changes postnatally, M arbors appear to mature by
      increasing arbor size and terminal branching complexity, whereas P arbors
      increase in complexity but not in size. These distinct programs of axon arbor
      development suggest that the periods of susceptibility of geniculocortical axon
      arbors to postnatal influences of the environment, and the types of plastic
      responses they potentially exhibit, are class-specific.

PMID- 7516702
TI  - Use of guanidinated dietary protein to measure losses of endogenous amino acids
      in poultry.
AB  - Guanidinated proteins when fed to non-ruminants provide values for both
      endogenous amino acid losses and amino acid digestibilities, provided that the
      homoarginine residues in the treated protein are randomly distributed. Earlier
      studies have established that guanidination has only minor effects on the
      structure of the protein and, in particular, on its susceptibility to
      proteolysis. Furthermore, we have confirmed that homoarginine behaves as a
      typical amino acid in the small intestine. Lysine residues in casein and soya
      bean protein, and in the proteins of cotton-seed meal, meat meal, soya-bean meal,
      maize, sorghum and wheat were converted to homoarginine by guanidination, the
      extent of conversion ranging from 37-68%. Sequential proteolysis in vitro of
      these guanidinated materials showed that the ratios of homoarginine to other
      amino acids remained unchanged for casein and soya-bean protein, indicating
      random distribution of homoarginine residues, but not for all the amino acids in
      meals and cereals. The use of guanidinated casein as the sole protein source in
      diets fed to broiler chickens allowed measurement of endogenous losses of amino
      acids under normal feeding conditions and calculation of true digestibilities of
      dietary amino acids at the ileum. Endogenous amino acid losses measured by the
      use of guanidinated casein (15.3 g/kg dry matter (DM) intake) were significantly
      higher (P < 0.001) than values obtained by feeding a N-free diet (5.4 g/kg DM
      intake), or by regression analysis to zero N intake (7.2 g/kg DM intake).

PMID- 7516704
TI  - Secondary structure of the nicotinic acetylcholine receptor: implications for
      structural models of a ligand-gated ion channel.
AB  - The secondary structure and effects of two ligands, carbamylcholine and
      tetracaine, on the secondary structure of affinity-purified nicotinic
      acetylcholine receptor (nAChR) from Torpedo has been studied using Fourier
      transform infrared spectroscopy (FTIR). FTIR spectra of the nAChR were acquired
      in both 1H2O and 2H2O buffer and exhibit spectral features indicative of a
      substantial alpha-helical content with lesser amounts of beta-sheet and random
      coil structures. The resolution enhancement techniques of Fourier self
      deconvolution and Fourier derivation reveal seven component bands contributing to
      both the amide I band and amide I' band contours in 1H2O and 2H2O, respectively.
      Curve-fitting estimates of the nAChR secondary structure are consistent with the
      qualitative analysis of the FTIR spectra as follows: 39% alpha-helix, 35% beta
      sheet, 6% turn, and 20% random coil. Of particular interest is the estimated
      alpha-helical content as this value places restrictions on models of the nAChR
      transmembrane topology and on the types of secondary structures that may
      contribute to functional domains, such as the ligand-binding site. The estimated
      alpha-helical content is sufficient to account for four transmembrane alpha
      helices in each nAChR subunit as well as a substantial portion of the
      extracellular and/or the cytoplasmic domains. FTIR spectra were also acquired in
      the presence and absence of 1 mM carbamylcholine and 5 mM tetracaine to examine
      the effects of ligand binding on the secondary structure of the nAChR. The
      similarity of the spectra, even after spectral deconvolution, indicates that the
      secondary structure of the nAChR is essentially unaffected by
      desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516703
TI  - Design and chemical synthesis of a neoprotein structural model for the
      cytoplasmic domain of a multisubunit cell-surface receptor: integrin alpha IIb
      beta 3 (platelet GPIIb-IIIa).
AB  - Integrins are a class of heterodimeric cell adhesion receptors involved in cell
      migration, cell anchorage, and cell-cell interactions. The cytoplasmic domains of
      integrins are of key importance in these activities. We have designed and
      chemically synthesized a 126 amino acid model protein (MP-1) containing both
      cytoplasmic tails of the platelet-derived integrin alpha IIb beta 3 covalently
      linked via a helical coiled coil. The coiled-coil tertiary structure was
      incorporated to mimic the membrane-spanning domain of the integrin and to act as
      a topological constraint fixing the two cytoplasmic tails in a parallel
      arrangement. This molecule, which contains two C-termini, was constructed by
      chemical dovetailing. The bromoacetylated and cysteinyl peptide synthons were
      unambiguously ligated through the formation of a thioether linkage. Ultraviolet
      circular dichroism (CD) spectroscopy has been performed on MP-1 and related
      compounds, confirming that a helical coiled coil is present within the MP-1
      molecule. Significantly, the helicity apparently extends beyond the predicted
      amphiphilic region of MP-1. Fluorescence measurements suggest that a defined
      tertiary structure has formed by the association of the two cytoplasmic domains.
      We conclude that this is a practical design strategy for the study of the
      cytoplasmic domain of multisubunit cell-surface receptors.

PMID- 7516705
TI  - Mechanism for the channel-opening reaction of strychnine-sensitive glycine
      receptors on cultured embryonic mouse spinal cord cells.
AB  - The strychnine-sensitive glycine receptor, a member of a superfamily of proteins
      involved in chemical reactions that regulate signal transmission between cells of
      the nervous system, forms an anion-specific transmembrane channel in response to
      glycine binding. A rapid-reaction technique, a cell-flow method with a 10-ms time
      resolution, was adapted for measurements with cultured embryonic mouse spinal
      cord cells containing glycine receptors. Whole-cell current responses resulting
      from the opening of glycine receptor channels were measured at pH 7.4, 22-24
      degrees C, and transmembrane voltages of -40 and -75 mV. Two different receptor
      forms, A alpha and A beta, were detected. At saturating glycine concentrations,
      an average of 70% of the whole-cell current amplitude was associated with form A
      alpha and 30% with A beta. The constants pertaining to the minimum mechanisms
      that account for the concentration of the two open-channel receptor forms over a
      100-fold range of glycine concentration were determined by cell-flow measurements
      of the current amplitudes and of the falling (desensitizing) rate of the current.
      The dissociation constant of the site controlling channel opening was 220 microM
      on the basis of three binding sites for A alpha and 380 microM on the basis of
      two binding sites for A beta. The channel-opening equilibrium constant, phi-I,
      was 170 for A alpha and 110 for A beta. The rate coefficients for
      desensitization, alpha and beta, associated with these two forms have maximum
      values of 0.7 and 0.1 s-1, respectively. The rates at which the receptors
      recovered from desensitization were also measured, using a double-flow mixing
      device, and were found to be 0.06 s-1 for A alpha and 0.02 s-1 for A beta. In the
      presence of 100 microM glycine, the apparent dissociation constant for the
      inhibitor picrotoxinin from receptor form A alpha was 80 microM, and that from A
      beta was 460 microM. This suggests that A beta contains beta-subunits (58 kD),
      because this subunit confers picrotoxinin insensitivity to glycine receptors
      (Pribilla, I., et al. (1992) EMBO J. 11, 4305). In the case of one receptor form
      (A alpha), the chemical mechanism and its constants led to two measurements that
      could be assessed by an independent method, the single-channel current-recording
      technique: (i) the fraction of receptor channels open at a given glycine
      concentration (ALn)o and (ii) the rate coefficient for desensitization.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7516706
TI  - Solution structure of residues 1-28 of the amyloid beta-peptide.
AB  - The three-dimensional solution structure of residues 1-28 of the amyloid beta
      peptide was determined using nuclear magnetic resonance spectroscopy, distance
      geometry, and molecular dynamic techniques. The nuclear magnetic resonance data
      used to derive the structure consisted of nuclear Overhauser enhancements,
      vicinal coupling constants, and temperature coefficients of the amide-NH chemical
      shifts. The beta-peptide is the major proteinaceous component of amyloid deposits
      in Alzheimer's disease. In membrane-like media, the peptide folds to form a
      predominately alpha-helical structure with a bend centered at residue 12. The
      side chains of histidine-13 and lysine-16 are close, residing on the same face of
      the helix. Their proximity may constitute a binding motif with the heparan
      sulfate proteoglycans. The molecular details of the structure shown here could
      facilitate the design of rational treatments to curtail the binding of heparan
      sulfate proteoglycans or to prevent an alpha-helix-->beta-sheet conversion that
      may occur during the early stages of amyloid formation in Alzheimer's disease.

PMID- 7516707
TI  - Alpha-deoxyadenosine, a major anoxic radiolysis product of adenine in DNA, is a
      substrate for Escherichia coli endonuclease IV.
AB  - Oligonucleotides containing a unique alpha-deoxyadenosine or tetrahydrofuran (a
      model abasic site) were synthesized using phosphoramidite chemistry. Repair
      enzymes from Escherichia coli, including endonucleases III, IV, and VIII,
      exonuclease III, formamidopyrimidine N-glycosylase, and deoxyinosine 3'
      endonuclease, as well as UV dimer N-glycosylases from T4 (den V) and Micrococcus
      luteus, were examined for their ability to recognize alpha-deoxyadenosine and
      tetrahydrofuran. In agreement with prior studies, a tetrahydrofuran-containing
      oligonucleotide was a substrate for endonuclease IV and exonuclease III, but not
      for the other repair enzymes. However, an oligonucleotide containing alpha
      deoxyadenine was a substrate only for endonuclease IV. Competitive inhibition
      studies with both substrates confirmed that the activity recognizing alpha
      deoxyadenine was endonuclease IV and not a possible contaminant in the
      endonuclease IV preparation. Using E. coli extracts, the activity that recognized
      alpha-deoxyadenine was dependent on nfo, the structural gene of endonuclease IV,
      further substantiating that endonuclease IV is the enzyme that recognized alpha
      deoxyadenine. Kinetic measurements indicated that alpha-deoxyadenosine was as
      good a substrate for endonuclease IV as tetrahydrofuran; the Km and Vmax values
      for both substrates were similar. Using substrates that were labeled at either
      the 3'- or 5'-terminus, endonuclease IV was shown to hydrolyze the phosphodiester
      bond 5' to either alpha-deoxyadenosine or tetrahydrofuran, leaving the lesion,
      alpha-deoxyadenosine or tetrahydrofuran, on the 5'-terminus of the nicked site.
      The ability of endonuclease IV to recognize alpha-deoxyadenosine suggests that
      endonuclease IV is able to recognize a new class of DNA base lesions that is not
      recognized by other DNA N-glycosylases and AP endonucleases.

PMID- 7516708
TI  - The role of posttranscriptional modification in stabilization of transfer RNA
      from hyperthermophiles.
AB  - The influence of posttranscriptional modification on structural stabilization of
      tRNA from hyperthermophilic archaea was studied, using Pyrococcus furiosus
      (growth optimum 100 degrees C) as a primary model. Optical melting temperatures
      (Tm) of unfractionated tRNA in 20 mM Mg2+ are 97 degrees C for P. furiosus and
      101.5 degrees C for Pyrodictium occultum (growth optimum, 105 degrees C). These
      values are approximately 20 degrees C higher than predicted solely from G-C
      content and are attributed primarily to posttranscriptional modification. Twenty
      three modified nucleosides were determined in total digests of P. furiosus tRNA
      by combined HPLC-mass spectrometry. From cells cultured at 70, 85, and 100
      degrees C, progressively increased levels of modification were observed within
      three families of nucleosides, the most highly modified forms of which were N4
      acetyl-2'-O-methylcytidine (ac4Cm), N2,N2,2'-O-trimethylguanosine (m2(2)Gm), and
      5-methyl-2-thiouridine (m5s2U). Nucleosides ac4Cm and m2(2)Gm, which are unique
      to the archaeal hyperthermophiles, were shown in earlier NMR studies to exhibit
      unusually high conformational stabilities that favor the C3'-endo form [Kawai,
      G., et al. (1991) Nucleic Acids Symp. Ser. 21, 49-50; (1992) Nucleosides
      Nucleotides 11, 759-771]. The sequence location of m5s2U was determined by mass
      spectrometry to be primarily at tRNA position 54, a site of known thermal
      stabilization in the bacterial thermophile Thermus thermophilus [Horie, N., et
      al. (1985) Biochemistry 24, 5711-5715]. It is concluded that selected
      posttranscriptional modifications in archaeal thermophiles play major stabilizing
      roles beyond the effects of Mg2+ binding and G-C content, and are proportionally
      more important and have evolved with greater structural diversity at the
      nucleoside level in the bacterial thermophiles.

PMID- 7516709
TI  - Dissecting the mechanism of protein disulfide isomerase: catalysis of disulfide
      bond formation in a model peptide.
AB  - As a model for understanding how protein disulfide isomerase (PDI) catalyzes
      disulfide bond formation in proteins, its action on a 28-residue disordered
      peptide containing only two cysteine residues has been examined. Disulfide
      formation in the peptide using the chemical reaction with small molecule
      thiol/disulfide reagents, such as oxidized and reduced glutathione or cystamine
      and cysteamine, occurs in two steps, via two alternative intermediate mixed
      disulfides between the reagent and either peptide cysteine residue. All
      thiol/disulfide forms of the peptide could be trapped and quantified, so the
      rates of their interconversion could be measured. Catalytic amounts of PDI
      increased the rates of these reactions. All rate enhancements were independent of
      the concentration of the peptide, indicating that it bound to PDI with an
      apparent Km of less than 3 microM. In the presence of glutathione, PDI
      accelerated the formation of both single mixed disulfide species, plus their
      subsequent rearrangement to form the peptide disulfide bond, but not interchange
      of the mixed disulfide glutathione between the two cysteine residues. In
      contrast, PDI did not catalyze the reaction of the reagent cystamine with the
      reduced peptide to form the mixed disulfide, nor the interchange of this mixed
      disulfide between cysteine residues, but did catalyze the subsequent
      intramolecular step of peptide disulfide bond formation to a similar extent as
      with the glutathione mixed disulfide. These effects on the two steps involving
      the mixed disulfides with glutathione or cystamine accounted for much of the
      overall catalytic effect of PDI on disulfide bond formation in the peptide,
      indicating that direct transfer of disulfide bonds from PDI to the peptide
      occurred less frequently. These findings demonstrate the utility of using such
      peptides as PDI substrates and have implications for the mechanism of action of
      PDI.

PMID- 7516710
TI  - Characterization of Ca2+ transport in Euglena gracilis mitochondria.
AB  - The present study was designed to establish the characteristics of the Ca2+
      fluxes in isolated mitochondria of the protist Euglena gracilis. Uptake of Ca2+
      and Sr2+ was supported by succinate and lactate oxidation. Ca2+ influx was
      slightly inhibited by 5 microM Ruthenium red and completely blocked by La3+ with
      a half-maximal inhibition attained at 50 microM. The addition of inorganic
      phosphate induced a 3-fold stimulation of Ca2+ uptake. Ca2+ uptake was inhibited
      by Mg2+ only in the absence of phosphate. Ca2+ efflux was induced by Na+, Li+ and
      K+ through a diltiazem-insensitive reaction. Ca2+ release, collapse of membrane
      potential and swelling were induced by Hg2+ and Cd2+ but not by
      carboxyatractyloside; cyclosporin A did not prevent the Ca2+ release induced by
      the heavy metal ions. Ca2+ uptake was achieved in the presence of 3 microM
      antimycin or 0.1 mM cyanide; this finding indicates that the alternative
      respiratory chain present in Euglena mitochondria can support this energy
      dependent reaction. The data obtained suggest similar pathways, but different
      regulatory mechanisms, for Ca2+ transport between protist and mammalian
      mitochondria.

PMID- 7516712
TI  - Use of hematopoietic growth factors in marrow transplantation.
AB  - Results of clinical trials in bone marrow transplantation (BMT) patients have
      shown that morbidity associated with myelosuppressive chemo- or radiotherapy is
      reduced in patients receiving hematopoietic growth factors such as recombinant
      human granulocyte colony-stimulating factor or recombinant human granulocyte
      macrophage colony-stimulating factor. Recombinant human granulocyte-macrophage
      colony-stimulating factor has been approved by the Food and Drug Administration
      to speed neutrophil recovery, to reduce the severity and duration of infection,
      and to shorten hospital stays of patients with lymphoid malignancy who undergo
      autologous BMT. Recombinant human granulocyte colony-stimulating factor is not
      approved by the Food and Drug Administration as therapy in BMT; however, results
      of phase I and phase II trials suggest similar beneficial effects in autologous
      BMT. Both molecules are well tolerated in patients undergoing autologous or
      allogeneic BMT. Other hematopoietic growth factors, such as recombinant Human
      macrophage colony-stimulating factor, recombinant human interleukin (rhIL)-3,
      rhIL-3-GM-CSF (rh-PIXY 321), rhIL-6, rhIL-1, rhc-kit ligand (rh-KL), and
      erythropoietin (rh-EPO), are also being studied singly or in combination in
      patients undergoing BMT. The use of hematopoietic growth factors in marrow
      transplantation is reviewed.

PMID- 7516711
TI  - Cytokines other than growth factors in bone marrow transplantation.
AB  - The role of cytokines during transplantation is currently an area of intense
      research. In particular, cytokines are increasingly appreciated as critical
      mediators of inflammatory responses to allogeneic tissue. Allogeneic bone marrow
      transplantation (BMT) involves cytokines not only in their capacity as
      hematopoietins but also as inducers of systemic inflammation after conditioning
      for BMT and during graft-versus- host disease (GVHD). GVHD is, in fact, a
      paradigm disease of systemic cytokine dysregulation, and the onset of severe
      acute GVHD can be considered a "cytokine storm." Advances in our understanding of
      the cytokine networks involved in BMT and GVHD should increase our ability to
      modify the complex interactions among cytokines and their cellular targets that
      lead to transplant-related morbidity.

PMID- 7516713
TI  - [Evaluation of the Chromotitre EIA test in the diagnosis of human brucellosis].
AB  - BACKGROUND: The aim of the study was to evaluate the diagnostic efficacy of
      Chromotitre EIA test for the diagnosis of human brucellosis and compare the same
      with other classical serologic test. METHODS: A prospective study was performed
      in 50 patients with active brucellosis. Thirty blood donors, 64 patients with
      different neoplastic and autoimmune infectious processes, 20 patients with
      history of brucellosis and 8 subjects with continuous exposure to Brucella at
      work were analyzed as the control group. RESULTS: Forty-five patients with
      brucellosis (90%) presented a positive IgM or IgG ELISA, 32 (62%) only IgM, 34
      (68%) only IgG and 22 (44%) both immunoglobulins were positive. The sensitivity
      and specificity of ELISA test jointly evaluating IgM and IgG was 90 and 68%,
      respectively with these numbers being 62 and 98% and 68% and 38% for ELISA IgM
      and ELISA IgG. A moderate correlation was found between ELISA IgM with Bengal's
      Rose test (r = 0.53, p = 0.003) and sero-agglutination (r = 0.63, p = 0.0001) and
      ELISA IgG with the Coombs test (r = 0.55, p = 0.003). Only acceptable concordance
      was observed between ELISA IgM and sero-agglutination (kappa = 0.55, p = 0.0001).
      CONCLUSIONS: The ELISA test evaluated was very useful for the detection of IgM
      antibodies but was found to be insufficient with respect to IgG antibodies.
      Despite the slight diagnostic efficacy of the ELISA IgG the combined parallel use
      of both immunoglobulins achieved a performance similar to that achieved with the
      classical tests.

PMID- 7516715
TI  - [Infection with hepatitis B and C viruses in the mentally retarded].
AB  - AIM: To study the prevalence of hepatitis C virus infection (HCV) and the
      associated risk factors in an institution for the mentally retarded, in addition
      to its relation with hepatitis B infection (HBV). METHODS: The presence of
      antibodies against the HCV (anti-HCV) and markers for the HBV was evaluated in 94
      mentally retarded subjects admitted to a single institution. Information
      concerning the sex, age, length of admission, type and degree of mental
      retardation, history of sexual promiscuity, surgery and blood transfusions was
      collected in every individual. RESULTS: The prevalence of infection by HBV was
      22.3%. Only one individual was detected as being positive for the HCV.

PMID- 7516714
TI  - [Evaluation of screening methods (catalase, sediment, reactive strip and Gram
      stain) in urinary tract infection in a Colombian university hospital].
AB  - BACKGROUND: To evaluate the catalase test as a screening method in urinary tract
      infection (UTI) versus sediment, reactive strip and Gram. METHODS: Two hundred
      forty-five's stain urine samples were prospectively analyzed in the Hospital
      Universitario San Ignacio de Bogota (Colombia). The culture was used as a
      reference test for the evaluation of the screening parameters in UTI patients.
      RESULTS: Of the 245 urine samples 45 were discarded. The remaining 200 urine
      samples were cultured being 100 positive and 100 negative. The former were
      analyzed by screening methods. The sensitivity and specificity of the catalase
      test was 97% and 94%, respectively with a positive predictive value of 94% and
      negative of 97%. The most frequently isolated microorganism was E. coli (84%),
      followed by Proteus sp. (6%). CONCLUSIONS: The use of the catalase test in
      urinary tract infection is a safe, economic and rapid method providing advantages
      due to its high sensitivity and specificity values, its good correlation with the
      different parameters evaluated in this study (sediment, strip, Gram's stain), and
      offers optimum diagnosis in urinary tract infection in developing countries such
      as Colombia.

PMID- 7516716
TI  - The role of interferons in the therapy of melanoma.

PMID- 7516717
TI  - Immunohistochemical detection of Coxiella burnetti in formalin-fixed placenta.

PMID- 7516718
TI  - Differential immunohistochemical staining of peste des petits ruminants and
      rinderpest antigens in formalin-fixed, paraffin-embedded tissues using monoclonal
      and polyclonal antibodies.

PMID- 7516720
TI  - Role of granulocyte colony-stimulating factor in the management of infection with
      Fusarium oxysporum in a neutropenic child.

PMID- 7516719
TI  - Disseminated Mycobacterium genavense infection in two patients with AIDS.
AB  - Mycobacterium genavense is a recently defined fastidious organism that has been
      identified as a cause of disseminated infection in patients with AIDS. We report
      the cases of two patients who had advanced AIDS and a clinical syndrome of fever,
      anorexia, abdominal pain, diarrhea, and weight loss. In addition, splenomegaly
      and lymphadenopathy were prominent in both cases, and in one patient's case
      radiographic findings were suggestive of splenic abscesses. Mycobacteria isolated
      from specimens of blood and bone marrow grew in liquid media but not on solid
      media. The results of DNA probe tests for Mycobacterium tuberculosis and
      Mycobacterium avium complex were false-positive for both patients. After
      treatment of the broth cultures to lyse red blood cells, the results of DNA probe
      tests were negative for these pathogens. Amplification and sequencing of 16S rRNA
      with use of the polymerase chain reaction indicated that the mycobacterial
      isolates from both patients had sequences identical to those previously reported
      for M. genavense. One patient survived 5 months after diagnosis, the other 2
      months after diagnosis; only one patient responded (transiently) to
      antimycobacterial chemotherapy.

PMID- 7516723
TI  - Suppression of experimental glomerulonephritis by the interleukin-1 receptor
      antagonist: inhibition of intercellular adhesion molecule-1 expression.
AB  - Interleukin-1 is a proinflammatory cytokine produced in glomerulonephritis.
      Blocking the action of interleukin-1 by the administration of the interleukin-1
      receptor antagonist (IL-1ra) has been shown to prevent renal function impairment,
      reduce glomerular injury, inhibit leukocyte infiltration, and suppress
      tubulointerstitial damage in experimental antiglomerular basement membrane
      disease. A key mechanism in the entry of leukocytes into the kidney is the
      interaction between the interleukin-1 inducible intercellular adhesion molecule-1
      (ICAM-1; CD54) and lymphocyte function-associated antigen-1 (CD11a/CD18).
      Therefore, this study investigated whether the inhibition of this mechanism was
      the means by which IL-1ra suppressed leukocyte infiltration in rat accelerated
      antiglomerular basement membrane glomerulonephritis. Disease was induced in two
      groups of six rats; animals were treated by constant sc infusion of recombinant
      human IL-1ra or saline from the initiation of disease until being euthanized 14
      days later. In saline-treated animals, there was marked up-regulation of ICAM-1
      in the glomerulus and interstitium, In which was associated with leukocyte
      infiltration. In particular, focal accumulation of CD11a+ and CD18+ cells was
      apparent in areas of tubulointerstitial damage exhibiting intense ICAM-1
      expression. IL-1ra treatment partially reduced glomerular ICAM-1 expression and
      leukocyte infiltration. However, IL-1ra treatment resulted in a dramatic
      inhibition of interstitial ICAM-1 expression, interstitial leukocyte
      infiltration, and tubulointerstitial damage. In conclusion, this study has shown
      that interleukin-1 is a major inducer of ICAM-1 expression within the renal
      tubulo-interstitium--a process associated with focal leukocyte infiltration and
      tubulointerstitial damage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516722
TI  - Glucocorticoid-dextran conjugates as potential prodrugs for colon-specific
      delivery: steady-state pharmacokinetics in the rat.
AB  - Chronic colitis, e.g., ulcerative colitis and Crohn's disease, is presently
      treated with glucocorticoids and other antiinflammatory agents. Side-effects
      limit chronic glucocorticoid therapy. The dose, and consequently the side
      effects, may be reduced by using prodrugs that selectively deliver drug to the
      colon. We previously synthesized glucocorticoid-dextran conjugates in which
      dexamethasone was attached to dextran (weight-average molecular weight = 72,600)
      using dicarboxylic acid linkers (succinate and glutarate). In the present study,
      dexamethasone-succinate-dextran and dexamethasone-glutarate-dextran were
      administered to two groups of male Sprague-Dawley rats by intragastric infusion.
      In two additional groups, disodium dexamethasone phosphate and dexamethasone
      hemisuccinate were each administered by subcutaneous infusion. In a fifth group,
      dexamethasone was administered by intragastric infusion. All groups were infused
      for sufficient time for steady state to be achieved. Colon-specific delivery was
      quantified using a drug-delivery index (DDI) in which steady-state dexamethasone
      concentrations in the cecum and colon were compared with those measured in blood
      after separate administrations of dexamethasone and dexamethasone-dextran
      conjugate. The colonic DDI values for dexamethasone-succinate-dextran and
      dexamethasone-glutarate-dextran were approximately seven and four, respectively.
      These values were a result of higher tissue concentrations and lower blood
      concentrations of dexamethasone after intragastric administration of the
      conjugates compared to subcutaneous and intragastric administration of
      dexamethasone. The pharmacokinetics of methyl-prednisolone was also investigated
      after subcutaneous infusion. Observed cecal and colonic tissue-to-blood ratios of
      19:1 and 12:1, respectively, showed that this drug is extensively delivered to
      the large intestine even after subcutaneous administration.

PMID- 7516724
TI  - Chronic idiopathic neutropenia associated with abnormal expression of granulocyte
      colony-stimulating factor mRNA of bone marrow stromal cells.
AB  - Chronic idiopathic neutropenia is an uncommon condition characterized by a low
      level of neutrophils without any causative disease. We report the details of 4
      patients whose stromal cytokine mRNA expressions were examined by reverse
      transcription polymerase chain reaction. Three patients showed a lower expression
      of granulocyte colony-stimulating factor (G-CSF) mRNA both in constructive and
      lipopolysaccharide (LPS)-induced conditions and normal colony forming unit
      granulocyte-macrophage (CFU-GM) from the bone marrow cells. One patient showed an
      increase of G-CSF mRNA and a decrease of CFU-GM. No abnormal expression of other
      cytokines including interleukin (IL)-1 beta, IL-6 and IL-8 were observed. These
      findings indicate that cytokine mRNA analysis of stromal cells is useful for
      elucidation of the etiology.

PMID- 7516721
TI  - Mutations in the M4 domain of Torpedo californica acetylcholine receptor
      dramatically alter ion channel function.
AB  - Site-directed mutagenesis was used to mutate alpha Cys418 and beta Cys447 in the
      M4 domain of Torpedo californica acetylcholine receptor expressed in Xenopus
      laevis oocytes. The M4 region is a transmembrane domain thought to be located at
      the lipid-protein interface. By whole-cell voltage clamp analysis, mutation of
      both alpha subunits to alpha Trp418 increased maximal channel activity
      approximately threefold, increased the desensitization rate compared with wild
      type receptor, and shifted the EC50 for acetylcholine from 32 microM to 13
      microM. Patch measurements of single-channel currents revealed that the alpha
      Trp418 increased channel open times approximately 28-fold at 13 degrees C with no
      effect on channel conductance. All of our measured functional changes in the
      alpha Trp418 mutant are consistent with a simple kinetic model of the
      acetylcholine receptor in which only the channel closing rate is altered by the
      mutation. Our results show that changes in protein structure at the putative
      lipid-protein interface can dramatically affect receptor function.

PMID- 7516725
TI  - Levels of L-T3 in maternal and foetal compartments following experimental
      modifications of the maternal thyroid state in rats.
AB  - In pregnant female rats, concentrations of tri-iodo-L-thyronine in maternal
      serum, amniotic fluid and placental tissue after 15, 18 and 20 days of gestation
      were measured by homologous radioimmune-analysis. The three experimental groups
      of pregnant rats were: 1) euthyroid (or control), 2) hypothyroid, provoked by
      iodine-deficient diet for two months before conception and during gestation, 3)
      hyperthyroid, provoked by subcutaneous injections of L-thyroxine during
      gestation. Maternal serum L-T3 was measured in order to check the thyroid state.
      Significant decreases in L-T3 concentrations were found at all stages of
      gestation in the amniotic fluid of hypothyroid group. The hormonal concentrations
      in the placental tissues were correlated with the different treatments (decreased
      in hypothyroid state and increased in hyperthyroid state). This could suggest
      that the transfer of maternal iodothyronines to the foetus influences its foetal
      thyroid development.

PMID- 7516726
TI  - Stimulation of prepubertal, pubertal and adult rat testis with low-intensity
      pulsed ultrasound.
AB  - Testes of prepubertal, pubertal and adult Wistar rats were stimulated with low
      intensity pulsed ultrasound for 20 min a day, for 7 days. No significant changes
      were found in the spermatogenic activity as well as in plasma LH and FSH levels
      following ultrasound treatment. The testicular androgenic activity, however, was
      significantly increased in prepubertal treated animals, in addition to a
      significant increase in seminal vesicle growth and secretory activity. In spite
      of normal androgenic levels, pubertal treated rats presented also an increase in
      the seminal vesicle secretory activity, thus suggesting a direct action of
      ultrasound on the gland.

PMID- 7516727
TI  - Glucose-induced secretion of ACTH-like products by rat pancreatic islets.
AB  - This work was performed to study the release of proopiomelanocortin (POMC)
      derived peptides from isolated pancreatic islets and the effect of ACTH--a member
      of that peptide family--on insulin secretion. Islets were incubated with 3,3 and
      16.6 mM glucose and insulin and ACTH-like products (ACTH-LP) were measured by
      radioimmunoassay. Glucose stimulated the simultaneous release of insulin and ACTH
      LP, the ACTH-LP concentration being higher when assayed with an antibody reacting
      with the N-terminus of ACTH. However, the increment in this release in the
      presence of the higher glucose concentration was larger when measured with an
      antibody against the ACTH mid-portion. Thus, although the islets would release
      more of a smaller ACTH-LP, 16.6 mM glucose would selectively increase the release
      of peptides of larger molecular size. Islets incubated with different
      concentrations of synthetic ACTH (50-500 pg/ml) increased the release of insulin
      in a dose-dependent manner. These results suggest that the release of endogenous
      ACTH-LP could contribute to the paracrine regulation of insulin secretion.

PMID- 7516729
TI  - Interactive effects of variations in [Na]o and [Ca]o on rat atrial spontaneous
      frequency.
AB  - The effects of varying the extracellular concentrations of Na and Ca ([Na]o and
      [Ca]o) on both, the spontaneous beating and the negative chronotropic action of
      verapamil, were studied in the isolated rat atria. Basal frequency (BF) evaluated
      by surface electrogram was 223 +/- 4 beats/min. in control Krebs-Ringer
      containing 137 mM Na and 1.35 mM Ca (N). It decreased by 16 +/- 3% by lowering
      [Na]o to 78 mM (LNa), 23 +/- 2% by lowering simultaneously [Na]o to 78 mM and
      [Ca]o to 0.675 mM (LNa+LCa) and 31 +/- 5% by lowering [Na]o to 78 mM plus
      increasing [Ca]o to 3.6 mM (LNa+HCa). At normal [Na]o, decrease (0.675 mM) or
      increase (3.6 mM) of [Ca]o did not modify BF; a reduction of ten times (0.135 mM
      of normal [Ca]o was effective to reduce BF by 40 +/- 13%. All negative
      chronotropic effects were BF-dependent. Dose-dependent bradycardia induced by
      verapamil was potentiated by LNa, LCa, and HCa. Independent but not additive
      effects of Na and Ca are shown by decreases in the values of [verapamil]o needed
      to reduce BF by 30% (IC30) with the following order of inhibitory potency: LNa >
      LCa > HCa > N, resulting LNa+HCa similar to LNa. The [verapamil]o that arrested
      atrial beating (AC) was also potentiated with the order LNa = LNa+LCa = LNa+HCa =
      LCa > HCa = N. The results indicate that rat atrial spontaneous beating is more
      dependent on [Na]o than on [Ca]o in a range of +/- 50% of their normal
      concentration. Also the enhancement of verapamil effects on atrial beating was
      more pronounced at LNa than at LCa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516728
TI  - Exercise-induced increase of plasma lactate is abolished by a pre-exercise
      epinephrine infusion.
AB  - The purpose of this study was to determine the effect of a higher than normal
      epinephrine content in skeletal muscles, on metabolic and hormonal adjustments
      during a subsequent exercise. Four groups of 10 rats were studied: two control
      groups, one at rest and one after an exercise leading to exhaustion on a
      treadmill (28 m.min-1, 8% grade) and two epinephrine-infused groups (EI), one at
      rest and one after the same type of exercise. Epinephrine-infused rats (EI)
      received an infusion of epinephrine (5 nM.kg.min-1, i.v.) for 20 minutes, and
      were rested 20 minutes before the start of the exercise or rest period. In the
      soleus muscle, epinephrine content was shown to be multiplied by 15 and 8 times
      the control values, respectively following 20 and 60 min after the end of the
      infusion. Control rats received a corresponding volume of sterile saline with the
      same schedule. The exercise lasted 49 +/- 14 vs 54 +/- 6 minutes respectively for
      EI and control rats (not significant). At rest, plasma concentrations of
      epinephrine, norepinephrine, plasma free fatty acids, glycerol, glucose and
      lactate as well as the glycogen content of the liver, the soleus, gastrocnemius
      lateralis and superficial vastus lateralis muscles were not different between
      saline and epinephrine-infused rats. Immediately after exercise, plasma lactate
      concentration was not increased after exercise in EI vs (2.26 +/- 0.39 vs 4.53 +/
      0.73 mM). One possible explanation of this observation is that re-released
      epinephrine might induce a vasodilation in the splanchnic or the skeletal muscle
      vascular beds and thus favors lactate clearance during exercise.

PMID- 7516730
TI  - [New studies on 3-dehydroecdysteroids in the biosynthetic pathway of ecdysone in
      Locusta migratoria].
AB  - Prothoracic glands of the locust, Locusta migratoria, incubated in vitro,
      converted in the same manner 3-dehydroketodiol (14 alpha-hydroxy-5 beta-cholest-7
      en-3,6-dione) tritiated either on the side chain (22,23,24,25)3H4 or on the
      nucleus (1,2)3H2. Conversion products always appeared in two forms: one oxidized
      at C-3 corresponding with 3-dehydroecdysteroids, and the other corresponding with
      "classical" ecdysteroids which are usually obtained by conversion of ketodiol.
      All the different intermediate ecdysteroids between ketodiol and ecdysone are
      presents. A non-hemolymphatic reductase is conceivably responsible for the
      conversion of 3-dehydroecdysteroids at one or several places in the course of the
      biosynthetic pathway. Quantitatively the two forms (oxidized or hydroxylated at C
      3) appeared in changeable ratios according to the different ecdysteroids but with
      a prevailing tendency to 1:1. The specificity of the conversion from nucleus
      tritiated-dehydroketodiol depended on an enormous production of polar degradation
      products (more than 50% of total radioactivity). Consequently the quantities of 3
      dehydro- and 3-hydroxy-ecdysteroids were lower than those which could be obtained
      after the conversion of side-chain-tritiated-3-dehydroketodiol. By means of an
      incubation with locust-larval-hemolymph, each 3-dehydroecdysteroid was totally
      (or at least in a great part: 3-dehydro-2-deoxyecdysone) converted into the
      corresponding reduced ecdysteroid. This fact confirms the reducing function of
      the hemolymph.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516731
TI  - Lactate threshold determination: a Monte Carlo comparison of two interpolation
      methods.
AB  - A heuristic model of the relation between blood lactate (L) and VO2 during
      exercise was used to assess the comparative merits of two methods of reference
      threshold determination: the habitual linear interpolation method (LT), and a new
      method using inverse parabolic (second degree) interpolation (PT); the new method
      capitalizes on the demonstrated curvilinear relation between blood lactate and O2
      uptake. Both types of interpolated thresholds were computed, and their error
      evaluated against the "true" 4-mmol lactate threshold. A combined parametric and
      Monte Carlo investigation showed that parabolic thresholds are generally
      superior, being less biased and more precise than their linear counterpart.

PMID- 7516732
TI  - Influence of the medium conditions on the 1-anilino-8-naphthalene sulfonate
      bovine serum albumin binding.
AB  - The effect of medium conditions on the binding of 1-anilino-8-naphthalene
      sulfonate (ANS) to bovine serum albumin (BSA) was studied. The intensity of
      binding was affected by the type of the monovalent salts used. While F- and Cl-
      decreased, SCN- and ClO4- promoted the binding. The relative order in which
      various anions influence the ANS binding to albumin process followed the
      lyotropic series. Some changes in the solvent structure affect the extent of
      binding. Urea exhibited two opposite effects. At low concentration urea induced
      the binding; at concentration above 1 M the binding was decreased. pH increase
      between 3 to 6 decreased dramatically primary and secondary sites. At pH higher
      than 6 only the secondary site affinity was increased. pH effect on the ANS
      binding to albumin is due to a participation of the acid and neutral
      conformational change of BSA.

PMID- 7516734
TI  - Effect of cold-exposure on rat organ blood flows.
AB  - Rat tissue blood flows and heart output were determined in adult Wistar rats
      under up to two hours of cold (4 degrees C) exposure, using radioactive 46Sc
      microspheres. Circulating glucose, lactate and triacylglycerol levels were also
      determined. Glucose concentrations increased with cold exposure in spite of the
      drainage of substrates induced by the activation of thermogenesis. Plasma
      triacylglycerol levels agree with a high involvement of fats in the sustenance of
      heat production. Cold-exposure had an immediate effect decreasing skin
      circulation, but increased that of muscle and brown adipose tissue. Kidney and
      intestine blood flows were maintained. In liver, blood flow increased
      progressively with cold-exposure. White adipose tissue showed--at first--low
      blood flow, but increased in parallel to that of liver. The data presented show a
      distribution of the blood in the body of the cold-exposed rat in which
      thermogenic responsibilities and supply of blood are evenly distributed
      throughout. The importance of haemodynamic changes in brown adipose tissue was
      considerable but the increased share of muscle blood flow suggests that it may
      have a global role in maintaining thermal homeostasis.

PMID- 7516733
TI  - Action of capsaicin and related peptides on the ionic transport across the skin
      of Rana esculenta.
AB  - Capsaicin at low concentrations increases the short circuit current (SCC) across
      frog skin. Simultaneous measurements of both transepithelial fluxes of 22Na or
      36Cl demonstrate that the SCC increase is due to stimulation of sodium active
      absorption. Capsaicin acts through the liberation of several peptides; thus these
      peptides were tested on the SCC across frog skin. Those more active are, in order
      of potency: Cyclic Calcitonin Gene Related Peptide (CGRP), Kassinin and
      Eledoisin, Substance P (SP) and Neurokinin A. Neurokinin B and Vasoactive
      Intestinal Peptide (VIP) have no effect. Also the actions of SP and CGRP are due
      mainly to stimulation of Na+ active absorption. A strict parallelism regarding
      the sensitivity to inhibitors (Naproxen, SQ22536 and CP96345) between SP, CGRP
      and Capsaicin strengthens the hypothesis that SP and CGRP are liberated by
      Capsaicin in this tissue.

PMID- 7516735
TI  - Prediction of exhaustion time from heart rate drift.
AB  - Beaury and Eclache (1978) proposed to extrapolate the drift of the heart rate up
      to maximal heart rate (Hrmax measured during an incremental maximal test) as a
      convenient way of estimation of the exhaustion tim (tlim) of an exercise at
      constant power (75 or 80% of Maximal Aerobic Power (MAP)). The purpose of this
      study was to evaluate this method of estimation of exhaustion time for a large
      range of power (60, 73, 86, 100 and 120% MAP). We compared the exercise duration
      calculated with this method (1limtheo) and the actual exhaustion time (tlim). The
      results showed that the subjects did not reach their maximal heart rate (Hrmax)
      at tlim and consequently that tlimtheo, calculated by extrapolation of heart rate
      drift, overestimated tlim, for all the loads in our study. The difference between
      tlimtheo and tlim (delta tlim expressed as a percentage of tlim) is significantly
      lower at 86% MAP than delta tlim at the other loads. It is likely that delta tlim
      is minimal around 80% MAP, i.e. the loads used in the study by Beaury and Eclache
      (1978). The values of heart rate (Hrlim), oxygen uptake (VO2lim) and oxygen puls
      (O2pulslim) measured at exhaustion suggested that the high level of energy cost
      is one of the main limiting factors at 86% MAP, in contrast with other loads.

PMID- 7516736
TI  - Blood levels of reduced/oxidized glutathione and plasma concentration of ascorbic
      acid during eccentric and concentric exercises of similar energy cost.
AB  - In an attempt to assess the possible oxidative stress associated with the
      transient exercise-induced activation of polymorphonuclear neutrophils (PMN), we
      compared the effects of eccentric and concentric exercises (downhill run: DR and
      uphill walk: UW, respectively) of equal duration (35 min) and similar energy cost
      (60% VO2max) on plasma levels of ascorbic acid ([AA]) and blood concentration of
      reduced ([GSH]) and oxidized ([GSSG]) glutathione. Eight healthy male subjects
      took part in this study. Plasma concentration of myeloperoxidase ([MPO]) was used
      as a specific marker of PMN activation. While there were no significant changes
      in [MPO] and [AA] in UW experiments, [MPO] increased (+80%) and [AA] decreased
      significantly during DR tests (P < 0.01 and P < 0.05, respectively). A
      significant negative relationship was observed between [AA] and [MPO] in DR
      experiments only (r = -0.49; P < 0.01). Mean (+/- SEM) basal GSH and GSSG
      concentrations, calculated by pooling the values measured before both tests, were
      0.54 +/- 0.02 and 0.12 +/- 0.007 mM, respectively. The blood concentration of
      these compounds remained practically unchanged in both exercise tests. These
      results confirm the role played by the eccentric component of muscle contraction
      in transient exercise-induced PMN activation and suggest that this activation was
      partly involved in the decrease in [AA] observed in DR experiments. The oxidant
      stress associated with the exercise protocol used in this study was insufficient
      to alter blood levels of reduced and oxidized glutathione.

PMID- 7516737
TI  - A new system for gastric emptying analysis using impedance measurement.
AB  - A tetra-polar electrical impedance device has been constructed to permit study of
      gastric emptying using a microcomputer. An alternative current of 100 kHz, 4 mM
      peak-to-peak, is injected through a pair of surface electrodes on the upper
      abdomen. The voltage variations picked up across the second pair of electrodes
      correspond to the variations of epigastric impedance in response to the applied
      current. The low frequency voltage corresponding to gastric emptying and
      recording noise is then conditioned and digitised at a sampling frequency of 1
      Hz. A parallel 8-bit signal is finally converted to standard serial form and
      sent, in real time, to a microcomputer via a serial port. In a process of off
      line analysis, the emptying trace was extracted from measured traces by taking
      successive Fast Fourier Transform (FFT) of length 64 points and was then fit by
      three mathematical models: linear, exponential and Weibull. The rate of emptying
      was calculated in terms of the time needed to achieve 50% emptying (T 1/2) from
      the best fit model. A clinical experiment was done in 20 healthy volunteers to
      investigate the reproducibility of the method and compared to a scintigraphic
      method. Successive measurements on the same subject gave statistically similar
      results and were statistically independent. No correlation has been observed
      between impedance and scintigraphic methods.

PMID- 7516738
TI  - Proton pumps in fish gill pavement cells?
AB  - The gill epithelium which comprises several types of cell faces multiple
      functions (O2/CO2 transfer, acid-base balance and ionic regulation). Little is
      known of the respective cellular localization of these functions. TEM examination
      of the catfish gill shows, in pavement cells, cytoplasmic vesicles and apical
      pits, both ornamented with studs reminiscent of the proton pumps observed in H+
      secretory epithelia. Ornamented apical pits are more frequently observed in
      acidotic fish. Taking together with our previous studies, this finding suggests
      that pavement cells play an important role, in addition to transfer of gas, by
      secreting protons. A new model of gill exchanges is proposed.

PMID- 7516740
TI  - [The protective action of adaptation to hypoxia in audiogenic epilepsy and its
      prolongation by using pharmacologic agents].

PMID- 7516739
TI  - Rapidly induced modulation of beta-N-acetylglucosaminidase activity in pancreatic
      islets.
AB  - The aim of this work was to determine the possible rapid modulatory effect of
      glucose on the activity of pancreatic islet lysosomal enzymes. For this purpose,
      beta-N-acetylglucosaminidase and beta-galactosidase activities were measured in
      homogenates of isolated rat islets after a 5, 15, 30 or 60-min exposure to either
      3.3 or 16.6 mM glucose. The enzyme activities were determined
      spectrofluorometrically by means of their respective 4-methylumbelliferyl
      derivatives as substrates. beta-N-acetylglucosaminidase activity measured in
      freshly isolated non-incubated islets was 5.482 +/- 0.281 mumol/mg protein/h at
      37 degrees C. In islets incubated with 3.3 mM glucose, this activity dropped
      significantly after 5 min and remained almost constant until the end of the
      incubation period. In islets incubated with 16.6 mM glucose, beta-N
      acetylglucosaminidase activity also decreased significantly at 5 min, and
      attained its lowest value after 15 min of incubation. After this interval, the
      activity began to recover and thereafter gained a value close to that measured in
      non-incubated islets by 60 minutes' time. Despite this ultimate recovery, the
      enzyme activities measured were significantly lower than those found in islets
      incubated with 3.3 mM glucose. beta-galactose activity in freshly isolated non
      incubated islets was 0.515 +/- 0.094 mumol/mg protein/h at 37 degrees C. This
      value remained almost unchanged throughout the incubation period in the presence
      of either 3.3 or 16.6 mM glucose. These results show that beta-N
      acetylglucosaminidase activity, a lysosomal hydrolase of pancreatic rat islets,-
      and only this enzyme--is modulated by glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516741
TI  - [Dynamic expression of the c-myc and Ca-ATPase genes in heart muscle during
      adaptation to repeated stress].

PMID- 7516742
TI  - [Location and fate of epithelial thymus cells of endodermal origin that
      synthesize cytokeratin 18].

PMID- 7516743
TI  - S-phase determination of immunoselected cytokeratin-containing breast cancer
      cells improves the prediction of recurrence.
AB  - Estimation of S-phase fraction in breast carcinomas with single parameter flow
      cytometry may include errors due to dilution of cancer cells by host cells. Use
      of tissue specific markers may to some extent correct for the effect of dilution.
      S-phase fraction was estimated by flow cytometry with and without immunoselection
      in 80 DNA-euploid breast carcinomas in stage I-II. The tumor tissue was
      mechanically disintegrated and fixed in ethanol. A primary antibody, specific for
      cytokeratins 8 and 18, was added before incubation with the secondary FITC
      conjugated antibody. S-phase fraction was calculated for both the gated
      (cytokeratin-positive) and the ungated cell population. An increasing proportion
      of tetraploid cells compared to diploid cells was found when the immunoselection
      method was used. The gated population tended to have a higher S-phase fraction
      than the ungated population. In univariate analysis S-phase fraction estimated
      from both ungated and gated cell populations yielded significant information for
      predicting recurrence when stratified for tumor size and nodal status. In
      bivariate analysis S-phase fraction of the gated population contributed
      prognostic information in addition to S-phase fraction of the ungated population
      when both variables were included in the analysis. Our conclusion is that S-phase
      fraction calculated from cytokeratin-positive cells provides prognostic
      information in addition to ungated S-phase values in DNA euploid breast
      carcinomas.

PMID- 7516745
TI  - Evaluation of antibody against AR142, a synthetic peptide derived from the core
      sequence of hepatitis C virus, in the diagnosis of non-A, non-B chronic liver
      disease.
AB  - We evaluated serum anti-hepatitis C virus (HCV) using a synthetic peptide (AR142)
      which includes an epitope in the core region of HCV. The incidence of anti-AR142
      in 98 patients with type non-A, non-B chronic liver diseases (NANB-CLD) was
      89.8%, while all the 28 patients with non-type C chronic liver diseases were
      negative for anti-AR142. Among 98 NANB-CLD patients, 74 were positive for both
      anti-AR142 and anti-C100-3, 23 showed discordant results, and one was positive
      for neither. Eighty-one NANB-CLD patients underwent reverse transcription
      polymerase chain reaction assay to detect viremia and 76 (93.8%) had a detectable
      level of HCV-RNA. Titers of anti-AR142 were not different among groups of
      different disease activities, genotypes of HCV, nor amount of serum HCV-RNA.
      These observations suggest that anti-AR142 could be a useful marker for chronic
      HCV infection.

PMID- 7516744
TI  - Normal and abnormal development of the blood-brain barrier.
AB  - The blood-brain barrier is responsible for the maintenance of the neuronal
      microenvironment. This is accomplished by isolation of the brain from the blood
      by the tight junctions that join endothelial cells in cerebral microvessels, and
      by selective transport and metabolism of substances from blood or brain by the
      endothelial cells. This review describes the growth and maturation of the brain
      vasculature, and the development of the special properties of the endothelia at
      the blood-brain interface. Evidence suggests that the development of the unique
      properties of the brain microvasculature is a consequence of tissue-specific
      interactions between endothelial cells of extraneural origin and developing brain
      cells. The cellular and molecular mechanisms that control these processes are as
      yet unknown but this review will include experimental studies which have used in
      vivo and in vitro systems to investigate what factors may be involved, and some
      pathological conditions in which abnormal barrier development is thought to be an
      important aspect of the disease process.

PMID- 7516746
TI  - Leukemoid reaction associated with diabetic ketoacidosis--with measurement of
      plasma levels of granulocyte colony-stimulating factor.
AB  - A 40-year-old man with diabetic ketoacidosis showed marked leukocytosis reaching
      60,970/mm3 which subsided within 5 days to a level of 4,140/mm3. He had no
      evidence of infection. During the entire clinical course, no elevation of
      granulocyte colony-stimulating factor (G-CSF) was observed. No case of leukemoid
      reaction associated with diabetic ketoacidosis has been reported with the
      determination of plasma G-CSF levels.

PMID- 7516747
TI  - Y353/B: a candidate multiple-copy spermiogenesis gene on the mouse Y chromosome.
AB  - There is evidence from Y Chromosome (Chr) deletion mapping that there is a gene
      on the long arm of the mouse Y Chr that is needed for the normal development of
      the sperm head. Since mice with partial Y long arm deletions show incomplete
      penetrance of the sperm head defect, whereas mice with no Y long arm show
      complete penetrance, it has been suggested that the 'spermiogenesis' gene may be
      present in multiple copies. A Y-specific genomic DNA sequence (Y353/B) has
      previously been described that is present in multiple copies on the long arm of
      the mouse Y and identifies testis-specific transcripts. We have suggested that
      Y353/B could be the proposed multiple copy 'spermiogenesis' gene. In support of
      this suggestion, we show here that mice with a partial Y long arm deletion
      associated with a 3.5-fold increase in the frequency of abnormal sperm heads have
      a marked reduction in genomic Y353/B copies and a corresponding reduction in
      Y353/B-related transcripts. Thus, the incompletely penetrant phenotype correlates
      with a reduction in Y353/B-related transcription. Furthermore, by in situ
      hybridization with a Y353/B riboprobe to testis sections, we show that the Y353/B
      related transcripts are confined to the round spermatid stage of spermiogenesis,
      just prior to the shaping of the sperm head. The transcripts sediment with the
      fraction of cytoplasmic RNA in adult testis that is loaded on polysomes,
      suggesting that the transcripts are actively translated.

PMID- 7516748
TI  - Secondary structures of lipid-associating peptides: a Fourier transform infrared
      study.
AB  - Four peptides from 20 to 28 residues in length were studied by Fourier transform
      infrared (FTIR) spectroscopy in solution and in complexes with
      dimyristoylphosphatidylcholine (DMPC). The four peptides included the 20-residue
      lipid-associating peptide, LAP-20, which was predicted to form an amphipathic
      helical structure in the presence of lipids, and three other peptides whose
      sequences had less amphipathic helix-forming properties. The complexes were shown
      by electron microscopy to be discoidal in shape with mean diameters of 21-27 nm.
      At the concentrations used for IR, the peptides appeared to form oligomers
      consisting of intermolecular beta-sheets. In the presence of lipids, the amount
      of beta-structure decreased; however, amounts of beta-structure were still
      approximately equal to amounts of alpha-helix. The IR results for LAP-20
      contradicted previous circular dichroism results that predicted 50%-90% alpha
      helix in DMPC complexes. Convex constraint analysis (CCA) deconvolution of the
      circular dicroism (CD) spectrum to estimate secondary structures predicted
      amounts of helix similar to those predicted by IR, but there was still
      substantial disagreement between IR and CD estimates of other secondary
      structures. For LAP-20 in complexes, CD predicted random structure. Possible
      physiological consequences of partial disordering of peptide structures are
      discussed.

PMID- 7516750
TI  - After intensive care--what then?
AB  - The total dependence that, from necessity, must be the lot of an intensive care
      patient can lead to a state of learned helplessness as they recover. In addition,
      the physical frailty of these patients further confounds their first attempts at
      independence. It is at this stage that patients need clear information about the
      road ahead and in a form that they can refer back to as needed when they are
      discharged to the general wards and then home. As many intensive care patients
      have little or no memory of the intensive care unit (ICU) afterwards and only
      gradually come to understand how ill they have been, the provision of an
      information booklet on discharge to the general wards seemed likely to be the
      most sensible approach. The booklet addresses topics such as transfer to the
      wards and possible problems patient might face during their convalescence. In
      addition common sense advice is offered to help patients regain their
      independence and control of their own health. The information is presented in a
      clear concise way and the booklet is liberally illustrated with cartoons.
      Relatives are encouraged to read the booklet as well and provisional results have
      shown it to be well received by both patients and relatives.

PMID- 7516751
TI  - Serum alpha 1-antitrypsin and alpha 2-macroglobulin in Alzheimer's and
      Binswanger's disease.
AB  - The deposition of beta A4-amyloid in senile plaques and small cerebral vessels is
      one of the pathological hallmarks of Alzheimer's disease. Recent data suggest
      that protease inhibitors such as alpha 2-macroglobulin may be involved in the
      process of forming beta A4 amyloid deposits. Compared to 34 persons without
      neurological diseases, the serum content of alpha 1-antitrypsin was increased in
      16 patients with Alzheimer's disease and 15 with Binswanger's disease. In the
      latter alpha 2-macroglobulin was also elevated in serum. Our results show no
      evidence of a blood-borne origin of the protein or peptid deposited in the walls
      of small vessels in Alzheimer's or Binswanger's disease. Nevertheless, the
      elevated proteinase inhibitor concentrations may play a role in the pathogenesis
      of these diseases.

PMID- 7516752
TI  - Expression of dystrophin-associated proteins in dystrophin-positive muscle fibers
      (revertants) in Duchenne muscular dystrophy.
AB  - The dystrophin-glycoprotein complex spans the sarcolemma to provide a linkage
      between the subsarcolemmal cytoskeleton and the extracellular matrix in skeletal
      muscle. In Duchenne muscular dystrophy (DMD), the absence of dystrophin leads to
      a drastic reduction in all of the dystrophin-associated proteins in the
      sarcolemma, thus causing the disruption of the dystrophin-glycoprotein complex
      and the loss of the linkage to the extracellular matrix. This is presumed to lead
      to sarcolemmal instability which could render muscle fibers susceptible to
      necrosis. In DMD, a very small percentage of muscle fibers show dystrophin
      staining along the sarcolemma, presumably due to a second in-frame deletion in
      the dystrophin gene. However, the functional significance of these rare
      dystrophin-positive muscle fibers (revertants) in DMD has been unclear. Here we
      report the co-expression of the dystrophin-associated proteins with dystrophin in
      revertants of DMD skeletal muscle. Our results suggest that the entire dystrophin
      glycoprotein complex is restored in revertants and, thus, the linkage between the
      subsarcolemmal cytoskeleton and the extracellular matrix is restored in these
      muscle fibers.

PMID- 7516749
TI  - Molecular diagnostics of polycyclic aromatic hydrocarbon biodegradation in
      manufactured gas plant soils.
AB  - Traditional methods for quantifying specific catabolic bacterial populations
      underestimate the true population count due to the limitations of the necessary
      laboratory cultivation methods. Likewise, in situ activity is also difficult to
      assess in the laboratory without altering the sample environment. To circumvent
      these problems and achieve a true in situ bacterial population count and activity
      measurement, new methods based on molecular biological analysis of bacterial
      nucleic acids were applied to soils heavily contaminated with polycyclic aromatic
      hydrocarbons (PAH). In addition, a naphthalene-lux reporter system was used to
      determine bioavailability of naphthalene within these soils. DNA extracted from
      seven PAH-contaminated soils and hybridized with the nahA gene probe indicated
      that the naphthalene degradative genes were present in all samples in the range
      of 0.06 to 0.95 ng/100 microliters DNA extract which was calculated to represent
      3.2 x 10(6) to 1.1 x 10(10) cells/g soil (assuming one copy of these genes per
      cell). 14C-naphthalene mineralization was observed in all contaminated soils with
      14CO2 mineralization rates ranging from 3.2 x 10(-5) to 304,920.0 x 10(-5)
      micrograms g soil-1 h-1. Phenanthrene, anthracene, and benzo(a)pyrene were
      mineralized also in several soils. Messenger RNA transcripts of nahA were
      isolated and quantified from 4 soils. Only one soil tested, soil B, was inducible
      with salicylate above the in situ nahA gene transcript level. Two of the soils, C
      and G, were already fully induced in situ. The naphthalene mineralization rate
      correlated positively with the amount of nahA gene transcripts present (r =
      0.99). Naphthalene was bioavailable in soils A, D, E, G, and N as determined by a
      bioluminescent response from the naphthalene-lux reporter system. Taken together,
      these data provided information on what the naphthalene-degrading bacterial
      population was experiencing in situ and what approaches would be necessary to
      increase activity.

PMID- 7516755
TI  - Analysis of streptomycin and dihydrostreptomycin in milk by liquid
      chromatography.
AB  - A method developed for the determination of the aminoglycoside antibiotics
      streptomycin and dihydrostreptomycin in tissues was applied to the analysis of
      fluid milk. Samples are extracted with 3.6% perchloric acid, and then injected
      onto a trace enrichment column, from which they are eluted onto a reversed-phase
      analytical column. The analytes are detected by fluorescence following postcolumn
      derivatization with 1,2-naphthoquinone-4-sulfonic acid. Recovery of analytes was
      in the range of 50-65% for skim or partially defatted fluid milk, while
      recoveries for homogenized whole milk were lower. Limits of quantitation were 10
      ppb for streptomycin and 20 ppb for dihydrostreptomycin.

PMID- 7516753
TI  - Effect of various commercially available enzymes in the liquid chromatographic
      determination with external standardization of thiamine and riboflavin in foods.
AB  - The efficacy of various commercially available enzymes in the determination of
      thiamine and riboflavin in foods was studied by liquid chromatography (LC) using
      external standards. Different enzymes, as well as the same enzyme produced by
      different manufacturers, very strongly affected the determination of both
      vitamins. The recoveries for different foods ranged from 85 to over 100% for
      thiamine and from 80 to 100% for riboflavin. The present LC method was accurate
      and precise when tested on a food and a feed reference material, and coefficients
      of variation were 5.5% for thiamine and 10% for riboflavin in a rye flour
      reference material tested for 8 months.

PMID- 7516756
TI  - [The physical and mental development of the child].

PMID- 7516754
TI  - Enzymatic/chemical analysis of dietary fiber.
AB  - The Uppsala methodology for rapid analysis and characterization of total dietary
      fiber, defined as the sum of dietary fiber polysaccharides (DFP) and Klason
      lignin, was studied. A sugar- and starch-free residue was prepared by treatment
      with a thermostable amylase and amyloglucosidase. Neutral DFP residues were
      quantified by gas chromatography as alditol acetates after acid hydrolysis of
      this residue, and the acid-insoluble fraction, Klason lignin, was determined
      gravimetrically. Uronic acid residues were quantified by decarboxylation of the
      original sample. The efficacy of the Uppsala methodology was tested with foods
      varying in fiber content and composition, including heat-treated samples. The
      present method allowed the analysis of up to 40 samples per week. It had good
      repeatability and coefficients of variation of 3-5% for the main fiber
      components. Fiber contents determined with the method were higher than those
      determined with a similar method that excludes Klason lignin and starch resistant
      to amylases but soluble in dimethyl sulfoxide and lower than those determined
      with an enzymatic/gravimetric method. Important aspects of fiber analysis, like
      enzyme purity and the recovery of soluble fiber on ethanol precipitation, also
      were investigated.

PMID- 7516757
TI  - [Use of intra-arterial chemotherapy in the treatment of malignant tumors in
      children].
AB  - Transcatheter arterial chemotherapy has been perfected in the treatment of 66
      patients with various severe malignant tumors. A total of 75 arterial cytostatic
      injections were made, out of them 57 were given in primary tumors and 18 in tumor
      metastases. The children's age ranged from 1 to 14 years. High arterial
      therapeutic doses in combination with extracorporeal blood purification by
      hemosorption in the treatment of hepatic metastases yielded 100% efficiency.
      Prolonged arterial chemotherapy for pulmonary metastases provided an excellent
      therapeutic effect. Thus, 75 arterial injections of cytostatics gave rise to 32%
      of complete remissions, 48% of partial remissions. There was no benefit in 20% of
      cases. Adverse reactions were absent.

PMID- 7516758
TI  - [A new method to determine the type of scar-changed tissue].
AB  - The mechanical parameters of the skin and scarring tissues were assessed in
      children aged 3-14 years who had various scar types, by using an ACA apparatus,
      which measures the propagation rates of superficial acoustic waves in the skin.
      It was found that the types (atrophic, hypertrophic, keloid) of scars could be
      significantly differentiated from the value of this parameter. The comparison of
      clinical and acoustic data shows high (as high as 90%) significance of the
      latter.

PMID- 7516759
TI  - [First trial of the clinical use of beforal in analgesia in children in long
      lasting microsurgical operations].

PMID- 7516760
TI  - [Long-term results of treatment of children with severe congenital intestinal
      obstruction].
AB  - A total of 295 children were operated on for severe ileus. The late outcomes of
      treating 88 children were studied for some months to 18 years. The assessment of
      the therapy results, the detection of causes of complications and the
      determination of the functional status were made by using a complex of study
      methods. Thirty-one children required surgical correction of complications. Five
      groups of children were identified and complications and reconstructive surgical
      techniques were determined and characterized.

PMID- 7516761
TI  - [Ecological immunodeficiency: immunogenetic aspects of its etiology and
      correction].
AB  - The examinations of auto-transport Kazakh drivers have indicated that there is a
      significant reduction in some immunological parameters HLA-B5 and HLA-DR5
      proliferative responses of lymphocytes to mitogens, production of interleukin-1
      and interleukin-2, activity of NK and LAK-cells. It is suggested that these
      impairments occur with their long-term exposure to automobile transport effluents
      (ATE), since the same changes in immunological parameters were found previously
      in the experiments with animals exposed to ATE for a long time. Some of the
      detected immunoresponsive disorders are associated with the availability of
      definite HLA antigens, such as HLA-B5 and HLA-P5. The new immunomodulating agents
      thymohexin (TH) and phyto-extraction drugs C4 and C6 used in vitro substantially
      restored the lower functional activity of immunocompetent cells and production of
      cytokines (thymohexin was particularly effective). The most marked recovery was
      observed in the drivers with the phenotype HLA-B6+ and HLA-P5+, i.e. in persons
      with maximally ATE-reduced immunological parameters.

PMID- 7516764
TI  - [Main trends in the studies of diabetes mellitus epidemiology].
AB  - At present there are three main research trends in the development of Russian
      epidemiology of diabetes mellitus: 1) study of the prevalence of diabetes
      mellitus and its factors that have an influence on its occurrence and development
      in various economic geographic areas of the country; 2) examination of the
      prognosis of its occurrence, and 3) exploration of the natural history and
      pathogenesis of diabetes mellitus under the natural living conditions of
      populations. The results of the epidemiological surveys which have been conducted
      since 1978 suggest that there are varying contrasting parameters in the spread of
      diabetes mellitus in different areas of the country, these are 0 to 4.1%. There
      is a relationship between diabetes mellitus and various factors, such as
      inheritance, obesity, dyslipoproteinemia, impaired carbohydrate and lipid
      metabolism, coronary heart disease, arterial hypertension, etc. There is a trend
      for diabetes mellitus to increase in the Russian Federation. Taking into account
      socioeconomic changes in our country, one cannot rule out the fact that the
      diabetes mellitus epidemiological situation and the pattern of its aggravation
      may change. So the studies in the third direction are acquiring its most
      importance.

PMID- 7516763
TI  - [Indications for surgery and methods of surgical correction of infundibuliform
      abnormality of the chest in children].
AB  - Based on the survey of 104 patients, a method has been developed for early
      diagnosis of progression of infundibuliform chest deformity (ICD), which defines
      indications for thoracoplasty in children over 2 years. A differential approach
      has been applied to the stabilization of the sternocostal complex, taking into
      account various ICD types. Experience in surgical management of 247 patients with
      simple and complex ICD types has been generalized. A procedure has been improved
      to stabilize the sternocostal complex with a metallic plate in critical ICD
      types. The sparing thoracoplasty variants have been developed for simple ICD
      types and Degree I progressive ICD ones, stabilizing the sternocostal complex
      with a niticolic brace and a CPK-22 apparatus in the modified resistant case.

PMID- 7516765
TI  - [Cryohemosorption--a method of removal of lipoprotein-antibody immune complexes
      and other atherogenic substances in patients with atherosclerosis].
AB  - The efficacy of extracorporeal cryohemosorption was estimated in the treatment of
      atherosclerotic patients in terms of the autoimmune theory of the pathogenesis of
      this disease. There was a slight decrease in the plasma levels of total
      cholesterol and triglycerides, there was over 2-fold reduction in the plasma
      levels of fibrinogen and fibronectin. All major components of apo B-containing
      lipoproteins and immunoglobulin G were found as part of the cryoprecipitate. An
      extremely high concentration of lipid hydroperoxides in the precipitate suggest
      that cryoprecipitation removes not only autoimmune complexes, but highly
      atherogenic peroxide-modified lipoproteins. The three-fold decrease in the levels
      of lipoprotein-antibody complexes resulted in lower atherogenicity of apo B
      containing lipoproteins. It is suggested that the mechanism responsible for
      beneficial clinical action of cryohemosorption sessions is largely associated
      with the removal of autoimmune lipoprotein-antibody complexes and peroxide
      modified apo B-containing lipoproteins than correction of lipid metabolism.

PMID- 7516766
TI  - [Allotransplantation of cultured neonatal androgen-producing Leydig cells].
AB  - The paper describes the procedure for grafting the cultural neonatal androgen
      producing Leydig's cells to the rat gonad, the status of the gonad and the graft
      in different periods following transplantation. The transplanted Leydig's cells
      preserve their structure within 6 months after allotransplantation. There is a
      normal spermatogenesis in the seminal canals. No phenomena of lymphoid
      infiltration, thrombosis of small vessels and other manifestations of
      histocompatibility were noted.

PMID- 7516762
TI  - [Comparison of the effectiveness of various types of therapy].
AB  - The paper deals with the analysis of one of the most characteristic problems in
      medical statistics,--comparison of the efficiency of various therapies (including
      those with different drugs) from clinical evidence; it gives a detailed account
      of the applied issues--identification of homogeneous groups and obtaining the
      estimates of distributed characteristics) of the required accuracy. Standardly,
      the best agent is identified, by comparing the mean values of the distributed
      characteristics. Such an approach cannot be considered satisfactory for some
      reasons. To arrive at a conclusion that it is advisable to introduce a new drug
      or a new treatment, the appropriate distributions should be more fully compared.
      A complete analysis of all these aspects has been made on a common basis and a
      general scheme of their practical decision has been identified.

PMID- 7516767
TI  - [Hybrid recombinant proteins: structure, properties and use].
AB  - The paper deals with the problem pertaining to immunotoxins which consist of two
      components, namely: catalytic (effector) and receptor-binding (ligand) ones. The
      immunotoxins are promising pharmaceutical drugs of a new generation, which are
      successfully used in clinical practice to treat tumor diseases, allergy, AIDS,
      and to transplant organs and tissues. Immunotoxins for the therapy of diabetes,
      autoimmune diseases, and bacterial, viral, and parasitic infections are being
      developed.

PMID- 7516770
TI  - [Evaluation of the effectiveness of vesicoureteral reflux treatment in children
      by endoscopic implantation of Teflon paste].
AB  - The paper assesses the results of treating 193 vesicoureteral refluxes of all
      forms and degrees in 135 children aged 1.5-14 years by endoscopic submucosal
      implantation of Teflon paste. The contraindication for surgery is acute urinary
      infection. With a flexible injection needle, Teflon paste (ETHICON, Germany) in
      doses 0.3 to 4.5 ml was infused under the ostium of the diseased ureter under
      endoscopic control to form a tight tubercle with closed ostia on the apex. Five
      (2.6%) cases displayed obstructive pyelonephritis in the early period. Late
      outcomes were followed for on 55 ureters. There was a positive result in 51
      (92.7%). In come cases repeated interventions were needed for acute liquidation
      of the reflux.

PMID- 7516769
TI  - [Scientific bases of health].
AB  - The usefulness of the change of paradigm, which treats health as a passive
      process, for the concept of activity, is substantiated: health is the ability of
      active self-protection... . The concept is worked out as a computer database, it
      generalizes the laws of self-smoothing, homeostasis, phylogenetic and ontogenetic
      regulating, following, compensation, self-disposing, systematic genesis and
      equilibration. The research work has shown that collection of mistakes does not
      make a barrier on the way of improving and does not limit the duration of health;
      the research work has also allowed to divide general regularities and individual
      affairs: the reactions' individuality is dropped by general adaptation syndrome,
      but because of non-typical situations the changes have an individual character
      and they cannot be generalized. The last idea gives specific requires on the
      control technology, if individuality (situationality) of conditions, state and
      abilities were taken into account. These regulations are hard to be done, but
      they do not have principle limitations. The author makes a conclusion: the
      perspective of using the models, uniting in the real time the abilities of men
      and the abilities of global computer networks, for the control and improvement of
      individual health, which adapt to the owner, is determined.

PMID- 7516768
TI  - [Extracorporeal irradiation of the total volume of circulating blood with low
      energy helium-neon laser].

PMID- 7516771
TI  - [Differential diagnosis and treatment of metatypic cancer].
AB  - Fifty one patients with metatypic carcinoma (MC), 10 with basalioma, and 10 with
      squamous cell carcinoma were clinically and immuno-morphologically studied. There
      were great differences in the localization of basal cell antigen in the epidermis
      during MC, basalioma, squamous carcinoma of the skin. Expression of fixed
      immunoglobulins A, M, G in tumor tissues revealed no significant differences.
      Fifty one patients underwent a complex treatment with prospidin in a total dose
      of 3,000-3,500 mg (in a daily dose of 100 mg) followed by near-focus X-ray
      therapy in a total dose of 3,000 Gy (a single dose being 500 Gy). Good immediate
      and late (the duration of the follow-up was as long as 5 years) results were
      obtained.

PMID- 7516772
TI  - [Possibilities of using Salmonella cya, crp mutants as vectors of an oral
      recombinant vaccine].
AB  - The Salmonella typhimurium B-2/1 double mutant with cya and crp mutations was
      obtained by a recombination process. The mutant exhibited a low virulence and
      inability to utilize citrate. In terms of these properties, the mutant differs
      from the wild-type strain. The mutant is able to persist in the body of mice,
      cattle, and monkeys, provoking the immune response to its oral administration.

PMID- 7516773
TI  - [Characteristics of blood supply and determination of growth proportionality of
      abnormal limb in children with partial gigantism].
AB  - The authors followed up 50 children with various types of partial gigantism of
      the upper and lower extremities. The specific features of vascularization in the
      diseased organs were defined and the prognostically important measure--the growth
      proportionality index--was determined. A classification of partial gigantism in
      children was proposed.

PMID- 7516774
TI  - Adhesion molecules in the lymphoid cell distribution in rheumatoid synovial
      membrane.
AB  - The staining pattern of a group of adhesion molecules on the immunoreactive cells
      in the lining layer of lymphocytic infiltrates of the rheumatoid synovial
      membrane was studied, using monoclonal antibodies by immunoperoxidase staining
      method against LFA-1, VLA-4, VLA-5, ELAM-1, and ICAM-1. The cells of the lining
      layer were strongly ICAM-1+ and VLA-5+, suggesting (1) that ICAM-1 may function
      to facilitate the adhesion of ICAM-1 bearing type A cells to type B cells, and
      (2) that the lining cells may utilize VLA-5 for anchorage to fibronectin at the
      surface of the synovial membrane. In the lymphocyte-rich and transitional area,
      the endothelial cells of the postcapillary venules were both ELAM-1+ and ICAM-1+.
      ICAM-1 staining of mononuclear cells was weak in lymphoid aggregates, but strong
      in the transitional area, indicating a paucity of ICAM-1 bearing cells in the
      lymphocyte-rich areas. On the other hand, LFA-1 staining was very strong in the
      lymphoid aggregates and only moderate in transitional areas. This suggests that
      the large numbers of T4 cells in the lymphocyte rich areas are sufficiently
      activated to express substantial levels of LFA-1, and also that the LFA-1
      molecule is an important receptor for emigration from postcapillary venules. In
      germinal center-like areas in lymphoid aggregates, most of the cells stained
      strongly for ICAM-1 and VLA-4, suggesting that the proliferation of B lymphocytes
      may be facilitated by LFA-1 and VLA-4 dependent T and B cell interaction. The VLA
      molecules stained in the transitional areas may provide appropriate adhesion and
      anchorage for the achievement of the variety of immune reactions which occur in
      these areas.

PMID- 7516775
TI  - Antibody raised to the short sequence from the zinc-finger domain of the EGR-1
      recognizes 102 KD protein in mouse fibroblasts.
AB  - EGR (early growth response) genes represent a family of the proteins whose
      structure includes a zinc finger domain(s) interacting with the specific site in
      regulatory sequences of different genes. Using as an antigen the short sequence
      RSNHLTTHIR from the middle of the zinc finger domain of EGR-1 we have generated a
      clone of the hybridoma cells producing the monoclonal antibody (mAb) that binds
      to 102 kD and 58 kD proteins, but apparently does not bind EGR-1 protein. The 102
      kD protein is probably made of the 58 kD subunit and another one of 44 kD.
      Expression of these proteins is strongly induced in serum stimulated mouse
      fibroblasts.

PMID- 7516777
TI  - G1244V: a novel missense mutation in exon 20 of the CFTR gene in a Bulgarian
      cystic fibrosis patient.

PMID- 7516776
TI  - Human microsomal epoxide hydrolase: genetic polymorphism and functional
      expression in vitro of amino acid variants.
AB  - Human microsomal epoxide hydrolase (mEH) is a biotransformation enzyme that
      metabolizes reactive epoxide intermediates to more water-soluble trans
      dihydrodiol derivatives. We compared protein-coding sequences from six full
      length human mEH DNA clones and assessed potential amino acid variation at seven
      positions. The prevalence of these variants was assessed in at least 37 unrelated
      individuals using polymerase chain reaction experiments. Only Tyr/His 113 (exon
      3) and His/Arg 139 (exon 4) variants were observed. The genotype frequencies
      determined for residue 113 alleles indicate that this locus may not be in Hardy
      Weinberg equilibrium, whereas frequencies observed for residue 139 alleles were
      similar to expected values. Nucleotide sequences coding for the variant amino
      acids were constructed in an mEH cDNA using site-directed mutagenesis, and each
      was expressed in vitro by transient transfection of COS-1 cells. Epoxide
      hydrolase mRNA level, catalytic activity, and immunoreactive protein were
      evaluated for each construct. The results of these analyses demonstrated
      relatively uniform levels of mEH RNA expression between the constructs. mEH
      enzymatic activity and immunoreactive protein were strongly correlated,
      indicating that mEH specific activity was similar for each variant. However,
      marked differences were noted in the relative amounts of immunoreactive protein
      and enzymatic activity resulting from the amino acid substitutions. These data
      suggest that common human mEH amino acid polymorphisms may alter enzymatic
      function, possibly by modifying protein stability.

PMID- 7516778
TI  - Urinary tract glycoprotein: distribution and antigenic specificity.
AB  - It has previously been demonstrated that the urinary tract contains a unique
      glycoprotein (GP1) that appears to serve a function in the clearance of
      pathogenic bacteria. We prepared a panel of monoclonal antibodies (mAbs) to human
      GP1 and examined its antigenic specificity and distribution in the human urinary
      tract. This was also observed in relation to another glycoprotein associated with
      infection, Tamm-Horsfall protein (THP), as well as to URO-5, a protein used in
      identifying the lower urinary tract. In enzyme-linked immunoadsorbent assays
      (ELISA), all of the GP1 mAbs reacted with GP1 prepared from both human urine and
      rabbit bladder mucosa. No immunoreactivity was observed with either THP mAbs or
      URO-5 mAbs. Western-blot analyses using GP1 mAbs with human urine GP1
      preparations detected a single band of approximately 50-52 kDa. Human urinary
      tract tissues were also examined by immunohistochemical techniques using the GP1
      mAbs, commercial THP, and URO-5 mAbs. In paraffin-embedded bladder sections, only
      GP1 mAbs reacted with the urothelium. Selective staining of distal collecting
      tubules, renal pelvis, and ureters was demonstrated for GP1 mAbs. Proximal
      convoluted tubules, loops of Henle, and Bowman's capsule failed to stain for GP1.
      In the same tissues, THP mAbs reacted with the thick and thin segments of
      medullary loops of nephrons (Henle's loops). URO-5 mAbs stained fresh frozen
      sections of bladder urothelium, distal collecting tubules, and portions of
      Henle's loops; however, they failed to stain paraffin-embedded tissue sections.
      These GP1 mAbs provide a new tool for biochemical and histochemical
      investigations of the mucin layer in both healthy and diseased urinary tract
      tissue.

PMID- 7516779
TI  - Interaction between bacteria and the lumenal bladder surface: modulation by
      pentosan polysulfate, an experimental and theoretical approach with clinical
      implication.
AB  - An attempt was made to interpret bacterial adsorption to the lumenal surface of
      the urinary bladder wall under normal and pathological conditions according to
      the DLVO theory of lyophobic colloid stability, which describes the interaction
      between a bacterium and the bladder-wall surfaces as a balance of attraction and
      repulsion forces. Computer modeling suggested that a decrease in the surface
      potential of the bladder wall may well explain an increased bacterial adsorption,
      possibly associated with bacterial cystitis. With the intent of preventing
      bacterial adsorption, treatment of bacterial cystitis by intravesical
      instillation of pentosan polysulfate (PPS) was evaluated. PPS is a polysaccharide
      with high affinity (4 +/- 2 mg/bladder) to the bladder. The attachment of PPS
      strongly depends on the intrinsic properties of the bacterial surface.
      Theoretical considerations indicate that either complete coverage of the
      bacterium with PPS or an absence of PPS affinity is a prerequisite for obtaining
      steric interaction or prevention of bacterial sorption. Experimentally, an
      absence of PPS affinity (0-0.7 microgram/mg bacteria) was found for bacteria
      commonly found during cystitis. Immunological treatment of superficial bladder
      cancer by bacillus Calmette-Guerin (BCG) depends on the interaction of BCG with
      the bladder wall. Improvement of the treatment may be obtained by increasing BCG
      adsorption. In this respect, the phenomenon of bridging in which PPS binds
      simultaneously to both BCG and the bladder-wall surface was investigated.
      Theoretical considerations and experimental results appeared to be in good
      agreement. It was found that BCG binds a considerable amount of PPS (3.4 +/- 0.3
      microgram/mg BCG). In a guinea pig model the theoretical considerations,
      indicating the occurrence of bridging at a low and narrow range of PPS
      concentrations, seemed to be confirmed. In contrast to a high PPS concentration
      of 10 mg/ml, at a low (0.1 mg/ml) PPS concentration a significant stimulation of
      the BCG-associated immune reaction(s) was observed. The results suggest that to
      obtain PPS-induced bridging between BCG and the bladder wall and to prevent
      steric interaction, PPS should be instilled prior to BCG, separated by extensive
      washout of free PPS.

PMID- 7516781
TI  - [Screening for the early diagnosis of prostatic carcinoma in Ossola: results
      after 1 year of effort].
AB  - Data concerning 1 year calls activity in the early diagnosis of the prostate
      cancer are published. Taking into consideration the results of the screening the
      Authors wonder whether its costs are justified.

PMID- 7516780
TI  - Treatment of renal calcium stone disease with the synthetic glycosaminoglycan
      pentosan polysulphate.
AB  - Glycosaminoglycans (GAGs) are potent inhibitors of calcium oxalate growth and
      aggregation. The synthetic GAG pentosan polysulphate (PPS) was used in the
      treatment of patients with renal calcium stone disease. Altogether, 121 patients
      were included in an open trial over a 3-year-period. The average stone episode
      rate and the stone operation rate were no different during treatment and in the
      pretreatment period. Altogether 48% of the patients were entirely stone-free
      during follow-up, whereas 29/56 patients who continued to form stones reported
      smaller stones that were more easily passed. It is concluded that there may be a
      role for PPS in the treatment of recurrent renal calcium stone disease, but a
      controlled study may be needed.

PMID- 7516782
TI  - Y body association with morphologic heterogeneity of human sperm.
AB  - OBJECTIVE: The purpose of this study was to determine a possible association
      between the Y body and sperm head shape, since sperm head shape may be a factor
      that influences the rate of migration of X- and Y-bearing sperm cells. MATERIALS:
      Sperm cell (n = 1,065) preparations from seven donors were fluorochrome stained
      for the Y body, and area and shape of Y body-positive and -negative cells were
      measured from digitized images. The distributions of the segregated cell
      population measurements were statistically analyzed nonparametrically. RESULTS:
      Of the total cells, 528 were Y body-positive and 537 were not, and the ratio
      (0.983) of the two cell categories, both within and between donors, was
      equivalent to the theoretical ratio of 1.0 expected for the X:Y sperm cell
      population. Sperm head area distributions were equal between the two populations.
      However, the length-width ratios of Y-bearing cells were significantly higher (P
      < .0001) and calculated roundness was significantly (P = .006) less than non Y
      body-bearing cells. CONCLUSIONS: The Y body may represent the Y chromosome.
      Furthermore, the Y body may impart a more ellipsoidal shape to sperm cells. Sperm
      shape may influence the migration rate of cells through cervical mucus such that
      differences in the male-to-female sex ratio of conceptuses, and at birth, may
      reflect a shape-imparted advantage in the migration rate of Y-bearing sperm in
      reaching the oocyte.

PMID- 7516783
TI  - RNA from normal anterior endoderm/mesoderm-conditioned medium stimulates
      myofibrillogenesis in developing mutant axolotl hearts.
AB  - In the axolotl, Ambystoma mexicanum, a recessive cardiac lethal mutation causes
      an incomplete differentiation of the myocardium. Mutant hearts do not contain
      sarcomeric myofibrils nor do they beat. We have previously shown that normal
      anterior endoderm, medium conditioned by endoderm, or total RNA extracted from
      endoderm stimulates differentiation of mutant hearts in culture as indicated by
      the presence of organized myofibrils and rhythmic contractions of the "rescued"
      mutant heart tube. In this study, to get a more highly purified sample of the
      "active" molecule, RNA extracted from endoderm-conditioned medium and was assayed
      for its ability to promote myofibrillogenesis in mutant hearts. Mutant heart
      mesoderm responded to conditioned-medium RNA in a dose-dependent manner.
      Proteinase K treatment of the RNA did not affect inductive activity, while
      digestion with RNase A completely abolished the ability to rescue mutant hearts.
      Confocal laser scanning microscopy of immunostained, organ-cultured hearts
      revealed that mutant hearts contain reduced amounts of the sarcomeric protein
      tropomyosin in an amorphous distribution, whereas normal and corrected mutant
      hearts contain tropomyosin primarily in organized myofibrils.

PMID- 7516785
TI  - Nosocomial septicaemia due to Enterobacter cloacae.

PMID- 7516784
TI  - Pharmacological interaction between neuropeptides and pethidine or fentanyl in
      rat spinal cord.
AB  - Male Wistar rats were treated with pethidine (PT) or fentanyl (FN) subcutaneously
      (sc) followed by intrathecal (ith) non analgesic doses of methionine- (MENK) or
      leucine-enkephalin (LENK), neurotensin, (NT), substance P (SP) or cholecystokinin
      octapeptide 26-33 (CCK-8). Then the antinociceptive effect was measured during 1
      h using tail-immersion test. LENK potentiated strongly PT and FN analgesia. MENK
      antagonized PT analgesia only transiently 30 min after administration and
      transiently potentiated FN analgesia. SP and CCK-8 potentiated significantly PT
      analgesia, whereas NT acted biphasically: increasing and then decreasing PT
      analgesia. SP, CCK-8 and NT augmented FN analgesia. Naloxone inhibited analgesia
      elicited by the studied opioids and neuropeptides. These data show that LENK
      affects similarly the analgesic effects of both studied opioids, whereas MENK
      acted differently on PT and FN analgesia. This may suggest that individual
      enkephalins have different pharmacological features when interacting with
      different analgesics. Also NT interacted differently with pethidine and fentanyl.

PMID- 7516786
TI  - Human platelet antigen-1 (Zw) typing of fetuses by analysis of polymerase chain
      reaction-amplified genomic DNA from amniocytes.
AB  - Prenatal typing for the human platelet antigens-1 (HPA) permits identification of
      a fetus at risk for neonatal alloimmune thrombocytopenia (NAITP) in cases of HPA
      1 incompatibility in which the father is heterozygous for the HPA-1a antigen.
      Diagnostic cordocentesis and phenotyping of the fetal platelets are used for this
      purpose. We applied allele-specific restriction enzyme analysis on polymerase
      chain reaction (PCR)-amplified DNA purified from amniocytes. This assays allows
      early second trimester typing for HPA-1 alleles. We were able to determine the
      genotype of three fetuses at risk. Iatrogenic fetal loss is lower with
      amniocentesis than with cordocentesis. Therefore, this technique is a welcome
      addition to the antenatal management of NAITP.

PMID- 7516787
TI  - Detection of HCV RNA in subjects with antibody to hepatitis C virus among the
      general population of Fukuoka, Japan.
AB  - Volunteer blood donors and aged people who came to hospitals for a thorough
      physical checkup were surveyed to evaluate the exact prevalence of hepatitis C
      virus (HCV) infection in the general population of Fukuoka, Japan. We tested for
      antibody to HCV (anti-HCV) by second-generation assay and, to distinguish active
      HCV infection from past resolved infection, we tested for HCV RNA in reactive
      serum samples by polymerase chain reaction. The prevalence of anti-HCV was 286
      (2.0%) of 14,341 subjects, increasing with advancing age, from 0.4% in the under
      29 age group to 12.0% in the over-70 age group. There were no differences between
      sexes. HCV RNA was detected in 170 of 286 (59.4%) anti-HCV-positive subjects. The
      ratio of HCV RNA-positive to anti-HCV-positive subjects was higher in males than
      in females (P < 0.05) and decreased with advancing age, from 72.2% to 46.5%. The
      prevalence of elevated alanine aminotransferase (ALT) was only 15.9% in subjects
      with HCV RNA, higher in males (21.4%) than in females (8.3%) (P < 0.05). This
      study revealed that the prevalence of anti-HCV was high in the aged population,
      but that the ratio of HCV RNA-positive to anti-HCV-positive subjects was low, and
      most of the HCV RNA-positive subjects had normal ALT levels.

PMID- 7516788
TI  - Age and sex-dependent alterations of serum amylase and isoamylase levels in
      normal human adults.
AB  - Total amylase and salivary- and pancreatic-type isoamylase levels were assayed in
      sera from 606 apparently healthy adults of different sex and age groups. There
      were significant differences in both total amylase and isoamylase levels,
      depending on age and sex, one of the characteristics being that levels of these
      three enzymes were significantly higher in the elderly group in both men and
      women than in other age groups. Another feature was that all of these enzyme
      levels were significantly greater in women in the third and fourth decade than in
      men. Age and sex differences should be taken into consideration in the evaluation
      of mild hyperamylasemia.

PMID- 7516791
TI  - Molecular characterization of pyrimidine biosynthesis genes from the thermophile
      Bacillus caldolyticus.
AB  - The genes encoding the six pyrimidine biosynthesis enzymes from the thermophile
      Bacillus caldolyticus were characterized by cloning and complementation in
      Escherichia coli, and by nucleotide sequence analysis. Nine cistrons are
      clustered within an 11 kb region of the chromosome, the gene order being: orf1
      pyrB-pyrC-pyrAa-pyrAb-orf2-p yrD-pyrF-pyrE. This organization of the cluster is
      very similar to that of the pyr operon of Bacillus subtilis. Different parts of
      the B. caldolyticus cluster were cloned in two orientations in the expression
      shuttle vector pHPS9. Complementation studies in B. subtilis established that
      expression of the pyr genes was dependent on the vector-borne promoter,
      suggesting that they are part of an operon, and that the native promoter of the
      operon had not been cloned. The deduced amino acid sequence of the individual
      cistrons showed 49 to 78% identity with the corresponding B. subtilis cistrons.
      Measurements of the aspartate transcarbamylase (pyrB), orotidine monophosphate
      decarboxylase (pyrF) and orotate phosphoribosyltransferase (pyrE) levels in cells
      grown under different conditions indicated that expression of the operon is
      repressed 7-9-fold by addition of uracil to the growth medium. Based on the
      nucleotide sequence in the intercistronic region between orf1 and pyrB a
      regulatory mechanism involving transcriptional termination and antitermination is
      proposed to control expression of the operon.

PMID- 7516790
TI  - [The morphological characteristics of the parasympathetic innervation of the
      pyloric sphincter in the cat].
AB  - The method of axonal transport of horse-radish peroxidase was used to detect the
      localization of neurons in the dorsal motor nucleus of the vagus nerve sending
      the axons to the pyloric sphincter. The investigation was carried out in cats.
      Under study were also morphological features of the nodular ganglion responsible
      for afferent innervation of the sphincter. The maximum amount of the
      corresponding cells are found in the dorsomedial part of the dorsal motor nucleus
      in the area from +1.0 to +2.0 mm (with respect to obex). The afferent neurons to
      which information comes from interoceptors of the sphincter zone along the vagus
      nerve fibers, are distributed in the left and right nodular ganglia almost
      evenly. The major part of these cells have the area of 300-800 mkm2.

PMID- 7516789
TI  - Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation.
AB  - A detailed evaluation of the antioxidant and pro-oxidant properties of lipoic
      acid (LA) and dihydrolipoic acid (DHLA) was performed. Both compounds are
      powerful scavengers of hypochlorous acid, able to protect alpha 1-antiproteinase
      against inactivation by HOCl. LA was a powerful scavenger of hydroxyl radicals
      (OH.) and could inhibit both iron-dependent OH. generation and peroxidation of ox
      brain phospholipid liposomes in the presence of FeCl3-ascorbate, presumably by
      binding iron ions and rendering them redox-inactive. By contrast, DHLA
      accelerated iron-dependent OH. generation and lipid peroxidation, probably by
      reducing Fe3+ to Fe2+. LA inhibited this pro-oxidant action of DHLA. However,
      DHLA did not accelerate DNA degradation by a ferric bleomycin complex and
      slightly inhibited peroxidation of arachidonic acid by the myoglobin-H2O2 system.
      Under certain circumstances, DHLA accelerated the loss of activity of alpha
      antiproteinase exposed to ionizing radiation under a N2O/O2 atmosphere and also
      the loss of creatine kinase activity in human plasma exposed to gas-phase
      cigarette smoke. Neither LA nor DHLA reacted with superoxide radical (O.2-) or
      H2O2 at significant rates, but both were good scavengers of
      trichloromethylperoxyl radical (CCl3O2.). We conclude that LA and DHLA have
      powerful antioxidant properties. However, DHLA can also exert pro-oxidant
      properties, both by its iron ion-reducing ability and probably by its ability to
      generate reactive sulphur-containing radicals that can damage certain proteins,
      such as alpha 1-antiproteinase and creatine kinase.

PMID- 7516792
TI  - Small cytoplasmic RNA of Bacillus brevis: transcriptional and phylogenetic
      analysis.
AB  - Using a DNA fragment of Bacillus subtilis scRNA as a probe, a Bacillus brevis
      gene encoding the small cytoplasmic RNA was cloned and characterized. B. brevis
      scRNA consists of 273 nucleotides; the sequence has comparatively low homology
      (approximately 70%) with other Bacillus sequences. Phylogenetic analysis
      indicated that B. brevis forms a line of descent distinct from other Bacillus
      species. However, despite the low overall homology, both functional nucleotide
      sequence and secondary structural features defined among signal recognition
      particle (SRP) RNA family members were well conserved.

PMID- 7516793
TI  - Isolation and characterization of the outer-membrane proteins of Burkholderia
      (Pseudomonas) pseudomallei.
AB  - Membranes obtained from whole-cell lysates of Burkholderia (Pseudomonas)
      pseudomallei (strain 319a) were separated into four fractions by sucrose density
      gradient centrifugation. Membranes were characterized by enzymic and chemical
      analyses, and by SDS-PAGE. Cytoplasmic membranes and two forms of outer membranes
      (OM-1, OM-2) were detected. The major outer-membrane proteins had M(r) values of
      70,000, 38,000, 31,000, 24,000 and 17,000. To determine which outer-membrane
      proteins were common to B. pseudomallei strains, OM-1 fractions from 12 different
      strains were prepared. SDS-PAGE analysis of these fractions demonstrated that the
      five major outer-membrane proteins were common to the strains tested. Further
      studies have shown that an M(r) 110,000 protein, which is oligomeric in that it
      migrates as an M(r) 38,000 protein upon heating at 95 degrees C and which is
      peptidoglycan-associated, serves as a porin in B. pseudomallei. Using
      proteoliposomes reconstituted from this protein and phospholipid, it was
      demonstrated by the liposome-swelling assay that this protein acts as a porin
      through which small saccharides may diffuse. Further characterization of this
      M(r) 38,000 protein will be important in delineating the role of this molecule in
      the permeability of the B. pseudomallei outer membrane.

PMID- 7516794
TI  - Reactivity of antibodies to heteroclitic peptides based on the Chlamydia
      trachomatis major outer-membrane protein.
AB  - One problem of peptide vaccines is that antibodies generated against them react
      poorly with the target sequence on the native protein. Using monoclonal
      antibodies (mAbs) to the serovar L1 type-specific epitope on the major outer
      membrane protein of Chlamydia trachomatis as our model in conjunction with the
      Pin Technology Epitope Scanning technique, we had previously identified the
      critical binding site at this epitope as DAVP. Amino acid substitution showed
      that AV were essential residues for binding. A series of structurally related
      (heteroclitic) peptides retaining AV were synthesized. Some of these were found
      to be much more reactive with the model mAb than peptides of cognate sequence. It
      was hypothesized that the DAVP peptide only approximated to the conformation of
      the homologous sequence in the native protein, whereas some of the flexible
      heteroclitic peptides produced conformations which more closely resembled the
      native constrained sequence. The key question was whether the most reactive
      heteroclitic peptide would also generate antibody capable of more efficient
      binding to the native protein. We therefore immunized mice with one of six
      heteroclitic peptides or one of two native sequence control peptides. The
      reactivity of these antisera with the peptide immunogens and with native
      chlamydial elementary bodies was then evaluated by enzyme immunoassay. Pooled
      antisera to two of the heteroclitic peptides reacted with significantly greater
      absorbance (P < 0.05) and at higher dilution with whole chlamydiae than did
      pooled antisera to the control peptides. This suggests that heteroclitic peptides
      may in some circumstances be useful to increase the reactivity of site-specific
      antibodies with epitopes on the native protein important for vaccine development
      or for serodiagnosis.

PMID- 7516795
TI  - Two types of 16S rRNA gene are found in Campylobacter helveticus: analysis,
      applications and characterization of the intervening sequence found in some
      strains.
AB  - In the recently described species Campylobacter helveticus, two sizes of PCR
      amplicon were detected with primers homologous to conserved regions of the 16S
      rRNA gene. A conventionally sized gene was sequenced from the type strain, NCTC
      12470, placing the new species as phylogenetically related to C. upsaliensis and
      the thermotolerant campylobacters. This nucleotide sequence enabled PCR primers
      to be designed for use in rapid molecular identification of C. helveticus and its
      closest phylogenetic relative, C. upsaliensis. When this assay was employed to
      characterize 22 'C. upsaliensis-like' isolates, twelve were identified as C.
      helveticus and nine as C. upsaliensis, in agreement with data obtained with a C.
      helveticus-specific DNA probe. A 550 bp amplicon internal to the 16S rRNA gene of
      C. helveticus was used to determine restriction fragment length polymorphisms
      (RFLPs) in genomic Southern blots, confirming that the copy number of the C.
      helveticus gene was three, and identifying nine 16S rRNA gene profiles. In 5/12
      C. helveticus isolates identified by PCR, an enlarged amplicon was detected. The
      enlarged 16S rRNA gene of one of these strains, NCTC 12838, was sequenced and
      shown to contain an atypical intervening sequence (IVS) of 148 nucleotides. The
      position and size of such an IVS was inferred in the other four isolates by PCR
      with primers 5' and 3' to its position in NCTC 12838. This is a first report of
      an IVS in the 16S rRNA gene of a eubacterium.

PMID- 7516796
TI  - Cloning the ribosomal RNA operons of Mycoplasma flocculare and comparison with
      those of Mycoplasma hyopneumoniae.
AB  - In contrast to other mycoplasma species the 16S/23S rRNA and 5S rRNA operons of
      Mycoplasma flocculare and Mycoplasma hyopneumoniae map at least 150 kb apart (20%
      of the genome). Both operons from M. flocculare have been cloned and sequenced.
      The 23S rRNA gene sequence showed 96.7% homology with the corresponding gene of
      M. Hyopneumoniae, equalling that found earlier for 16S rRNA and confirming the
      close phylogenetic relationships of these organisms. A possible upstream promoter
      was identified. Sequence elements upstream and downstream from each structural
      gene could form a stem needed for maturation of the immature rRNA transcript to
      mature 16S and 23S rRNA. We also identified two possible stem-and-loop sequences
      3' to the 23S rRNA gene. The 5S rRNA gene itself also showed high homology with
      the corresponding structural gene of M. hyopneumoniae, although the upstream and
      downstream sequences were highly heterologous.

PMID- 7516797
TI  - Effect of hepatocyte growth factor/scatter factor and other growth factors on
      motility and morphology of non-tumorigenic and tumor cells.
AB  - Using an automated cell analyzer system, the effect of hepatocyte growth
      factor/scatter factor (HGF/SF), epidermal growth factor (EGF), basic fibroblast
      growth factor (bFGF), endothelial acidic fibroblast growth factor (a-FGF),
      platelet derived growth factor (PDGF), and recombinant human insulinlike growth
      factor (IGF) on the motility and morphology of Madin-Darby canine kidney (MDCK),
      rat hepatomas, C2, and H5-6 and murine mammary carcinoma (EMT-6) cells was
      investigated. Treatment of MDCK cells with HGF/SF, bFGF, EGF, and a-FGF resulted
      in an increase in average cell velocity and in the fraction of moving cells.
      Cells treated with the PDGF and IGF did not show significant alterations in
      velocity. MDCK cells treated with each growth factor were classified into groups
      of "fast" and "slow" moving cells based on their average velocities, and the
      average morphologic features of the two groups were quantitated. Fast-moving
      cells had larger average area, circularity, and flatness as compared to slow
      moving cells. Factors that stimulated cell movement also induced alterations in
      cell morphologic parameters including spreading, flatness, area, and circularity.
      HGF/SF also scattered and stimulated motility of C2 and H5-6 hepatoma cells. In
      contrast to MDCK cells, there was no significant difference between the
      morphology of the fast moving and slow moving C2 and H5-6 cells. These studies
      suggest that growth factor cytokines have specific effects on motility of normal
      and tumor cells.

PMID- 7516798
TI  - Growth of wool follicles in culture.
AB  - A procedure for the culture of isolated wool follicles from Merino sheep is
      described. Follicles were microdissected from midside skin samples of 2-yr-old
      wethers and transferred, individually, to 24-well tissue culture plates. When
      maintained in supplemented Williams' E medium containing 5 to 10% fetal bovine
      serum (FBS), insulin, hydrocortisone, and a trace element mixture, fibre growth
      rates of 40 to 80 microns/day were observed. Follicles maintained their
      morphologic integrity for up to 7 days, incorporated [methyl-3H]thymidine into
      DNA and [35S]methionine into intermediate-filament keratins of the growing fiber.
      Insulin and hydrocortisone stimulated fiber growth at concentrations of 10
      micrograms/ml and 50 ng/ml, respectively, but higher doses were inhibitory. The
      growth of fibers in response to hydrocortisone and the changes in follicle
      morphology was similar to those induced in skin after systemic administration of
      cortisol in vivo. A positive interaction between hydrocortisone and trace
      elements for follicle survival and hydrocortisone, insulin, and FBS for fiber
      growth was also found. The successful culture of Merino sheep follicles provides
      a model with which to study the direct influence of endocrine, nutritional and
      local factors on wool keratin synthesis independently of systemic shifts in the
      animals' metabolism.

PMID- 7516799
TI  - Facilitatory effects of selective agonists for tachykinin receptors on
      cholinergic neurotransmission: evidence for species differences.
AB  - 1. Exogenous tachykinins modulate cholinergic neurotransmission in rabbit and
      guinea-pig airways. We have investigated the effect of selective tachykinin
      receptor agonists and antagonists on cholinergic neurotransmission evoked by
      electrical field stimulation (EFS) of bronchial rings in rabbit, guinea-pig and
      human airways in vitro to assess which type of tachykinin receptor is mediating
      this facilitatory effect. 2. Bronchial rings were set up for isometric tension
      recording. Contractile responses to EFS (60 V, 0.4 ms, 2 Hz for 10 s every min)
      and exogenous acetylcholine (ACh) were obtained and the effects of selective
      tachykinin agonists and antagonists were investigated. 3. In rabbit bronchi the
      endogenous tachykinins, substance P (SP) and neurokinin A (NKA) (10 nM)
      potentiated cholinergic responses to EFS (by 287.6 +/- 121%, P < 0.01 and 181.4
      +/- 56.5%, P < 0.001 respectively). 4. The NK1 receptor selective agonist,
      [Sar9]SP sulphone (10 nM) evoked a maximal facilitatory action on cholinergic
      responses of 334.9 +/- 63% (P < 0.01) (pD2 = 8.5 +/- 0.06) an effect which was
      blocked by the selective NK1-receptor antagonist, CP 96,345 (100 nM) (P < 0.05)
      but not by the NK2 receptor antagonist, MEN 10,376 (100 nM). The NK2 receptor
      selective agonist, [beta Ala8]NKA(4-10) (10 nM), produced a maximum enhancement
      of 278 +/- 83.5% (P < 0.01) (pD2 = 8.7 +/- 0.1) an effect which was blocked by
      MEN 10,376 (100 nM) (P < 0.05) and not by CP 96,345. [MePhe7]NKB, an NK3 receptor
      selective agonist was without effect. 5. The rank order of potency of NK2
      receptor antagonists against enhancement of cholinergic responses by [Beta
      Ala8]NKA(4-10) was MEN 10,376> L 659,877> R 396. This pattern together with the
      observation of the full agonist activity of MDL 28,564 indicates that the NK2
      receptors in the rabbit bronchus are similar to those which are present in the
      rabbit pulmonary artery.6. Neither [Sar9]SP sulphone (5 nM) nor [Beta Ala8]NKA(4-
      10) (1 nM) had any effect on contractile responses to ACh (10 MicroM) suggesting
      a pre-junctional mechanism of action.7. By contrast, in guinea-pig bronchi only
      the NK1-receptor agonist [Sar9]SP sulphone (3 nM) was effective in enhancing
      cholinergic neurotransmission but the effect was relatively small (maximal
      enhancement 25.7 +/- 5.5%, P<0.01). In human bronchial rings all the selective
      neurokinin agonists were without effect on cholinergic neurotransmission.8. These
      results suggest that tachykinins may play an important role in modulating
      cholinergic neurotransmission in rabbit (via NK1 and NK2 receptors) and guinea
      pig airways (via NK1 receptor) but have no demonstrable effect on human airways

PMID- 7516800
TI  - A study of the mechanism of MDMA ('ecstasy')-induced neurotoxicity of 5-HT
      neurones using chlormethiazole, dizocilpine and other protective compounds.
AB  - 1. An investigation has been made in rats into the neurotoxic effect of the
      relatively selective 5-hydroxytryptamine (5-HT) neurotoxin, 3,4
      methylenedioxymethamphetamine (MDMA or 'Ecstasy') using chlormethiazole and
      dizocilpine, both known neuroprotective compounds and also gamma-butyrolactone,
      ondansetron and pentobarbitone. 2. Administration of MDMA (20 mg kg-1, i.p.)
      resulted in a 50% loss of cortical and hippocampal 5-HT and 5-hydroxyindole
      acetic acid (5-HIAA) 4 days later. This reflects the long term neurotoxic loss of
      5-HT that occurs. Injection of gamma-butyrolactone (GBL; 400 mg kg-1, i.p.) 5 min
      before and 55 min after the MDMA provided substantial protection. Pentobarbitone
      (25 mg kg-1, i.p.) using the same dose regime was also protective, but
      ondansetron (0.5 mg kg-1 or 0.1 mg kg-1, i.p.) was without effect. 3. MDMA (20 mg
      kg-1) had no significant effect on striatal dopamine concentration 4 days later
      but did produce a small decrease in 3,4-dihydroxyphenylacetic acid (DOPAC)
      content. There were few significant changes in rats given MDMA plus GBL,
      ondansetron or pentobarbitone. 4. A single injection of MDMA (20 mg kg-1, i.p.)
      resulted in a greater than 80% depletion of 5-HT in hippocampus and cortex 4 h
      later, reflecting the initial rapid release that had occurred. None of the
      neuroprotective compounds (chlormethiazole, 50 mg kg-1; dizocilpine, 1 mg kg-1;
      GBL, 400 mg kg-1; pentobarbitone, 25 mg kg-1) given 5 min before and 55 min after
      the MDMA injection, altered the degree of 5-HT loss. 5. Acute MDMA injection
      increased striatal dopamine content (28%) and decreased the DOPAC content. In
      general, administration of the drugs under investigation did not significantly
      alter these MDMA-induced changes. Both chlormethiazole and GBL produced a greater
      increase in dopamine than MDMA alone, but this was apparently an additive effect
      to the action of either drug alone. 6. The 5-HT loss 4 h following administration
      of the neurotoxin p-chloroamphetamine (2.5 mg kg-1,i.p.) was not affected by
      chlormethiazole or dizocilpine. p-Chloroamphetamine did not appear to alter
      striatal dopamine metabolism.7. None of the protective drugs inhibited the
      initial 5-HT loss following MDMA, rendering unlikely any proposal that they are
      protective because they inhibit 5-HT release and the subsequent formation ofa
      toxic indole derivative. All the protective compounds (unlike ondansetron)
      probably inhibit dopamine release in the striatum. Since the neurotoxic action of
      some substituted amphetamines is dependent on the integrity of nigro-striatal
      neurones, this fact may go some way to explain the protective action of this
      diverse group of compounds.

PMID- 7516802
TI  - Suramin and reactive blue 2 are antagonists for a newly identified purinoceptor
      on rat megakaryocyte.
AB  - 1. The effects of purinoceptor antagonists on ATP-induced oscillatory K(+)
      currents in rat isolated megakaryocytes were investigated. 2. Both reactive blue
      2 (RB-2), a selective antagonist of the P2Y purinoceptor, purinoceptor, at
      concentrations of 0.3-10 microM and suramin, a non-selective P2 purinoceptor
      antagonist, at 1-30 microM blocked the ATP-induced oscillation in a concentration
      dependent manner. 3. RB-2 and suramin also blocked the ADP-induced K(+)-current
      oscillation at the same concentration range as in the case of ATP. However, both
      suramin and RB-2 had no effect on thrombin- and inositol 1,4,5-trisphosphate
      (IP3)-induced K+ current oscillation, indicating that they act as specific
      purinoceptor antagonists. 4. Thus, the purinoceptors on megakaryocytes show the
      properties of the P2 subtype according to their blockade by antagonists.

PMID- 7516803
TI  - Prevention by phosphodiesterase inhibitors of antigen-induced contraction of
      guinea-pig colonic smooth muscle.
AB  - 1. The ability of various phosphodiesterase (PDE) inhibitors to reduce the
      initial and/or late response to ovalbumin (OVA) in isolated strips of guinea-pig
      colonic smooth muscle from sensitized animals was examined. 2. Both the initial
      and late responses to OVA (0.05 mg ml-1) were inhibited by the non-selective PDE
      inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX, EC50 = 26.0 and 6.1 microM,
      respectively), and the selective inhibitors of low Km cyclic AMP specific PDE
      (PDE IV), (R)- and (S)-rolipram. The (S)-isomer (EC50 = approximately 1.0 microM
      for both responses) was about 10 fold less potent than the (R)-isomer (EC50 =
      approximately 0.1 microM for both responses). 3. Zaprinast, a selective inhibitor
      of the cyclic GMP-specific PDE (PDE V) inhibited only the late response (EC50 =
      1.4 microM). 4. SK&F 94120, a selective inhibitor of the cyclic GMP-inhibited low
      Km cyclic AMP PDE (PDE III), inhibited the initial response (45.9 +/- 11.9%, P <
      0.05) at the highest concentration tested (100 microM), and had no effect on the
      late response. 5. The results suggest that PDE inhibitors, especially PDE IV
      inhibitors, can attenuate the contractile response of guinea-pig colon to OVA.

PMID- 7516801
TI  - Effects of cyclopiazonic acid on phenylephrine-induced contractions in the rabbit
      ear artery.
AB  - 1. Upon stimulation with phenylephrine, the rabbit ear artery displays
      endothelium-regulated rhythmic contractions, which may be attributed to the
      periodical activation of the dihydropyridine-sensitive Ca2+ channel, presumably
      regulated by the Ca(2+)-activated K+ channel. The effect of cyclopiazonic acid
      (CPA), an inhibitor of the Ca(2+)-ATPase of the sarcoplasmic reticulum (SR), on
      phenylephrine-induced contractions was examined in endothelium-denuded rabbit ear
      arteries suspended in an organ chamber for isometric tension recordings. 2.
      Phenylephrine-induced tonic contractions were converted to rhythmic ones by the
      addition of CPA. 3. The CPA-induced rhythmic contractions were abolished by the
      blockade of the dihydropyridine-sensitive Ca2+ channel and the Ca(2+)-activated
      K+ channel by nifedipine and charybdotoxin, respectively. In contrast,
      glibenclamide, an ATP-sensitive K+ channel antagonist, had no effect on the CPA
      induced rhythmic responses. 4. CPA attenuated both Ca2+ repletion by the SR and
      Ca2+ influx across the plasmalemma without having a significant effect on Ca2+
      release from the SR, as evaluated by phenylephrine-induced contractions. In
      contrast, these three parameters were not altered by the presence of the
      endothelium. 5. These findings indicate that the CPA-induced rhythmic
      contractions in the endothelium-denuded rabbit ear artery may be induced by the
      same ionic mechanism as endothelium-regulated rhythmic responses, by which the K+
      channel could regulate the probability of the Ca2+ channel being opened. The CPA
      induced rhythmic contractions may correlate with the inhibitory effects of CPA on
      the SR function, although this is not true for the endothelium-regulated rhythmic
      contractions.

PMID- 7516804
TI  - Mechanism underlying substance P-induced relaxation in dog isolated superficial
      temporal arteries.
AB  - 1. In helical strips of dog superficial temporal arteries with intact
      endothelium, substance P elicited a concentration-related relaxation with an EC50
      of 2.8 (2.4-3.2) x 10(-10) M. 2. The relaxant response to the peptide in low
      concentrations (1-4 x 10(-10) M) sufficient to produce approximately half maximal
      relaxation was not inhibited by indomethacin, but was markedly suppressed by NG
      nitro-L-arginine (L-NOARG), a nitric oxide (NO) synthase inhibitor, and by
      endothelium denudation. 3. High concentration (10(-7) M) of substance P produced
      marked relaxations in endothelium-intact strips. Removal of the endothelium
      attenuated the relaxation, and indomethacin or tranylcypromine suppressed the
      endothelium-independent relaxation. In indomethacin-treated strips with intact
      endothelium, L-NOARG attenuated but did not abolish the relaxation. The residual,
      L-NOARG-resistant relaxation was not significantly inhibited by ouabain,
      glibenclamide or tetraethylammonium. 4. Substance P (10(-7) M) increased the
      levels of cyclic GMP and cyclic AMP. The increase in cyclic GMP was abolished by
      endothelium denudation and treatment with L-NOARG, whereas the cyclic AMP
      increment was abolished by indomethacin. 5. Three different mechanisms may be
      involved in the substance P-induced relaxation: (1) an endothelium-dependent
      relaxation mediated by the release of NO from the endothelium, resulting in an
      increase of cyclic GMP (low and high concentrations of the peptide); (2) an
      endothelium-independent relaxation in association with cyclic AMP increment
      caused by prostaglandin I2 released from subendothelial tissues (high
      concentration), and (3) another endothelium-dependent relaxation possibly
      mediated by unidentified mediator(s) released from the endothelium (high
      concentration).

PMID- 7516806
TI  - Design and fabrication of biodegradable polymer devices to engineer tubular
      tissues.
AB  - Engineering new tissues by transplanting cells on polymeric delivery devices is
      one approach to alleviate the vast shortage of donor tissue. However, it will be
      necessary to fabricate cell delivery devices that deliver cells to a given
      location and promote the formation of specific tissue structures from the
      transplanted cells and the host tissue. This report describes the design and
      fabrication of a polymeric device for guiding the development of tubular
      vascularized tissues, which may be useful for engineering a variety of tissues
      including intestine, blood vessels, tracheas, and ureters. Porous films of poly
      (D, L-lactic-co-glycolic acid) have been formed and fabricated into tubes capable
      of resisting compressional forces in vitro and in vivo. These devices promote the
      ingrowth of fibrovascular tissue following implantation into recipient animals,
      resulting in a vascularized, tubular tissue. To investigate the utility of these
      devices as cell delivery devices, enterocytes (intestinal epithelial cells) were
      seeded onto the devices in vitro. Enterocytes were found to attach to these
      devices and form an organized epithelial cell layer. These results suggest that
      these devices may be an appropriate delivery vehicle for transplanting cells and
      engineering new tubular tissues.

PMID- 7516805
TI  - The effects of BTS 54,505, a metabolite of sibutramine, on monoamine and
      excitatory amino acid-evoked responses in the rat dorsolateral geniculate nucleus
      in vivo.
AB  - 1. The effects of BTS 54,505, the primary amine metabolite of the non-tricylic
      putative antidepressant sibutramine, on the responses evoked by visual
      stimulation and ionophoretic application of noradrenaline (NA), 5
      hydroxytryptamine (5-HT) and excitatory amino acids (EAAs) in the rat
      dorsolateral geniculate nucleus (dLGN) have been investigated. 2. Ionophoretic
      application of 5-HT to dLGN neurones attenuated visually-evoked (n = 46), NMDA
      evoked (n = 21) and AMPA-evoked responses (n = 21), while ionophoretic
      application of NA potentiated visually-evoked activity in these cells (n = 27).
      3. Simultaneous application of BTS 54,505 with 5-HT (over 120 s) resulted in a
      prolongation of the recovery time (i.e. the period required by a neurone to
      recover by 50%, RT50) from the 5-HT-mediated suppression of discharge activity
      (approximately 275% increase in RT50). BTS 54,505 also prolonged the recovery
      time from a NA-mediated potentiation of firing (approximately 450% increase in
      RT50). These effects on recovery time are attributed to the inhibition of uptake
      of both 5-HT and NA by BTS 54,505. The amplitude of the response to 5-HT or NA
      was unaffected by co-ejection of BTS 54,505. 4. Ionophoretic application of N
      methyl-D-aspartate (NMDA) produced a current-dependent increase in neuronal
      firing, as did application of the non-NMDA receptor agonist alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA). A simultaneous 120 s application of
      BTS 54,505 inhibited the NMDA response in all cells studied (mean ED50 = 16 +/- 5
      nA) but had no effect on AMPA-evoked activity in the majority of the same cells
      (n = 15/21).5. Short 10 s applications of BTS 54 505, at ejecting currents (>30
      nA) that attenuated NMDA-evoked activity in all cells studied, had no effect on
      either response amplitude or recovery time from ionophoretic application of 5-HT,
      suggesting that inhibition of NMDA-evoked activity by BTS 54 505 was not mediated
      by 5-HT uptake blockade.6. These results suggest that BTS 54 505 inhibits NMDA
      evoked activity, and the observation that this effect is unlikely to be due to
      raised levels of endogenous 5-HT following monoamine uptake blockade indicate
      that BTS 54 505 may interact directly with the NMDA receptor ionophore complex.

PMID- 7516808
TI  - Prostate-specific antigen corrected for prostate volume improves differentiation
      of benign prostatic hyperplasia and organ-confined prostatic cancer.
AB  - OBJECTIVE: To determine whether the ratio of PSA and prostate volume provides
      additional useful information for the discrimination of benign prostatic
      hyperplasia from prostatic carcinoma. PATIENTS AND METHODS: Since 1989, a
      prospective study has been in progress involving 229 patients (49 with locally
      confined prostatic carcinoma, 180 with benign prostatic hyperplasia) to establish
      whether the ratio of prostate-specific antigen (PSA) and prostate volume,
      determined by transrectal ultrasound (longitudinal x anterior-posterior x
      transverse diameter x 0.52), allows a better differentiation than the absolute
      PSA values. RESULTS: In this population of patients with prostatic disease, the
      positive predictive value for diagnosis of a prostatic carcinoma was 26% with an
      absolute PSA threshold value of 4.0 ng/ml, and 36% at a threshold value of 10
      ng/ml. With a threshold value of the PSA/prostate volume ratio of 0.25 ng/(ml x
      cm3), the positive predictive value was 56% compared with 93% for a threshold
      value of 0.4 ng/(ml x cm3). CONCLUSION: The ratio PSA/prostate volume is a
      superior method for the diagnosis of prostatic carcinoma both with regard to its
      sensitivity and its specificity in patients with absolute PSA values in excess of
      4 ng/ml.

PMID- 7516809
TI  - Carcinoma of the prostate mimicking lymphoma.

PMID- 7516810
TI  - Supporting evidence for negative modulation by protons of an ion channel
      associated with the N-methyl-D-aspartate receptor complex in rat brain using
      ligand binding techniques.
AB  - The addition of L-glutamic acid (Glu) alone, both Glu and glycine (Gly) or
      Glu/Gly/spermidine (SPD) was effective in potentiating [3H]5-methyl-10,11-dihydro
      5H-dibenzo[a,d]cyclohepten-5,10- imine (MK-801) binding before equilibrium to an
      ion channel associated with the N-methyl-D-aspartate (NMDA) receptor complex in
      brain synaptic membranes extensively washed and treated with Triton X-100. The
      binding dependent on Glu almost linearly increased in proportion to decreasing
      proton concentrations at a pH range of 6.0 to 9.0 in external incubation medium,
      while a Gly-dependent portion of the binding increased with decreasing proton
      concentrations up to a pH of 7.5 with a plateau thereafter. In contrast, the SPD
      dependent binding increased in proportion to decreasing proton concentrations up
      to a pH of 7.0 with a gradual decline thereafter. Similar profiles were also
      obtained with [3H]MK-801 binding at equilibrium, with an exception that
      significant binding of [3H]MK-801 was detected in the absence of any added
      agonists. The potency of SPD to potentiate [3H]MK-801 binding before equilibrium
      increased in proportion to decreasing proton concentrations, with those of both
      Glu and Gly being unchanged. In contrast, the ability of (+)MK-801 to displace
      [3H]MK-801 binding at equilibrium was not significantly affected by a decrement
      of external proton concentrations from pH 7.5 to pH 8.5 in the presence of
      Glu/Gly and Glu/Gly/SPD added. However, similar changes in external proton
      concentrations did not similarly affect binding of several radioligands for the
      NMDA and Gly domains on the receptor complex. Decreasing proton concentrations
      were effective in exponentially potentiating binding of [3H]SPD at a pH range of
      6.0 to 9.0 without virtually altering [3H]D,L-alpha-amino-3- hydroxy-5-methyl
      isoxazole-4-propionic acid binding. In addition, [3H]kainic acid binding markedly
      decreased with decreasing proton concentrations only in the presence of Ca2+
      ions. These results suggest that protons negatively modulate neuronal responses
      mediated by the NMDA receptor ionophore complex through interference with opening
      mechanisms of the channel domain without disturbing association processes of the
      endogenous agonists with the respective recognition domains in rat brain.
      Moreover, possible modulation by protons of responses mediated by the kainate
      receptor in the presence of Ca2+ ions at concentrations that occur in vivo is
      also suggested.

PMID- 7516807
TI  - Effect of platelet activating factor (PAF) on the formation of blood vessels in
      subcutaneous implants in mice.
AB  - Angiogenesis accompanies inflammatory processes and many other pathological
      conditions. We have studied the effect of platelet-activating factor (PAF) a well
      known inflammatory mediator, as a promoter of angiogenesis in the sponge implant
      model in mice. Development of blood vessels and blood flow were monitored by use
      of a 133Xe washout technique. The results showed PAF to have angiogenic activity,
      which was inhibited by WEB 2086, and the PAF-induced vasculature to have normal
      pharmacological reactivity.

PMID- 7516811
TI  - Whole-cell patch-clamp recordings from visualized bulbospinal neurons in the
      brainstem slices.
AB  - The purpose of this study was to develop a method for electrophysiological
      characterization of retrogradely labeled bulbospinal neurons in the specific
      cytoarchitectonic regions in the brainstem slices. Several days after the spinal
      cord was injected with the carbocyanine dye, DiI, retrogradely labeled
      bulbospinal neurons were visualized by epifluorescence optics in the brainstem
      slices with the aid of a silicon intensifier tube (SIT) camera. Labeled somata
      were routinely seen in the caudal raphe nuclei, rostroventral medial and lateral
      portions of the medulla, the A5 group and in other medullary sites known to
      project to the spinal cord. Electrophysiological properties of the DiI-labeled
      neurons were assessed by whole-cell recordings using micropipettes filled with
      biocytin. The slices were subsequently processed for dual visualization of
      biocytin and serotonin or a marker for noradrenergic neurons, tyrosine
      hydroxylase (TH). The electrophysiological properties of bulbospinal neurons were
      correlated with their morphology and neurochemical content. This technique may be
      useful in other areas of CNS for studying morphology, neurochemical content and
      physiology of retrogradely labeled neurons.

PMID- 7516812
TI  - Effects of ageing on sensory nerve function in rat skin.
AB  - Human studies have shown an age-related decrease in modulation of skin vascular
      reactivity by sensory nerves that correlates with a decline in wound repair
      efficacy. Using a vacuum-induced blister model in the rat hind footpad, we have
      investigated age-related changes in pre- and post-terminal activity of primary
      afferents involved in skin neurovascular function. Changes in local skin blood
      flow were monitored using a laser Doppler flowmeter. Pre-terminal stimulation was
      achieved by electrical stimulation of the distal end of the sciatic nerve (10 V,
      15 Hz and 0.5 ms) in three groups of young, old and neonatally pretreated
      capsaicin rats (3, 24 and 3 months old, respectively). The effect of post
      terminal stimulation, achieved using local perfusion of 1 microM substance P (SP)
      over the blister base, was examined in young (3 months old), mature (12 months
      old) and aged (24 months old) rats. In addition to changes in SP responsiveness,
      other post-terminal changes studied included changes in smooth muscle reactivity
      to sodium nitroprusside (SNP), which acts directly on smooth muscle and to
      endothelial cell function using N-nitro-L-arginine (L-NORAG), a selective
      inhibitor of nitric oxide synthesis and endothelium-dependent relaxation.
      Electrical stimulation of the sciatic nerve in young rats induced an increase in
      local blood flow (within 1 min) that was maintained during the stimulation
      period, while the capsaicin group and the old group showed a significantly
      increased latency and decreased amplitude of the response.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7516813
TI  - Nitric oxide synthase immunoreactivity colocalized with NADPH-diaphorase
      histochemistry in monkey cerebral cortex.
AB  - The distributions of reduced nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d) and nitric oxide synthase (NOS) containing neurons and the
      extent of NADPH-d and NOS colocalization have been analyzed by histochemical and
      immunocytochemical techniques in the neocortex of Macaca fuscata monkeys. NADPH-d
      positive cells were consistently also NOS positive and presented a relatively
      uniform distribution from area to area, but area-specific differences were
      observed in the pattern of distribution of fiber plexuses.

PMID- 7516814
TI  - Epitope analysis of isoforms of the major allergen Phl p V by fingerprinting and
      microsequencing.
AB  - The major allergen of timothy grass pollen (Phleum pratense), designated as Phl p
      V, consists of isoallergenic components of 38 and 32 kDa with pl values of 5.2
      7.5 and 4.8-5.9, respectively. The different-sized proteins reveal similarities
      in IgE reactivity, N-terminal sequence and protein staining. For epitope analysis
      of these allergens a combination of enzymatic cleavage of electrophoretically
      separated proteins and immunoblotting techniques with subsequent N-terminal
      sequencing was performed. After isolation of the components from two-dimensional
      PAGE gels, proteins were enzymatically cleaved and separated by SDS-PAGE. By
      endoproteinase Glu-C cleavage six IgE-reactive fragments of each 32 kDa protein
      and three of each 38 kDa allergen were obtained. Microsequencing of the fragments
      revealed internal sequences that did not show any similarities between the
      different-sized allergens. Therefore, we assume only slight structural variations
      among allergens of similar sizes, whereas the 32 and 38 kDa proteins reveal great
      differences.

PMID- 7516815
TI  - In vitro basophil histamine-releasing activity of circulating IgG1 and IgG4
      autoanti-IgE antibodies from asthma patients and the demonstration that anti-IgE
      modulates allergen-induced basophil activation.
AB  - In this study we have examined the relationship between the in vitro basophil
      histamine-releasing activity of human IgG anti-IgE, isolated as euglobulin
      fractions from sera of asthmatic patients, and its IgG1/IgG4 subclass
      distribution. In particular, we have investigated whether IgG anti-IgE modulates
      allergen-induced basophil activation. The study has revealed that only a small
      proportion of IgG anti-IgE samples triggered histamine release from basophils of
      an asthmatic individual (4/21; 19%), a hay fever sufferer (4/10; 40%) and a
      healthy person (7/21; 33%). The basophil histamine-releasing activity of IgG anti
      IgE did not seem to be determined by the IgG1/IgG4 subclass composition of the
      IgG anti-IgE preparation used. Furthermore, we have demonstrated that autoanti
      IgE antibodies modulate allergen-induced basophil histamine release. The three
      modulatory effects exerted by IgG anti-IgE antibodies on allergen-triggered
      basophil activation (i.e. additive, synergistic and blocking) were not dependent
      on the subclass nature of IgG anti-IgE or the use of histamine-releasing anti-IgE
      preparations. Our data suggest that IgG anti-IgE antibodies in asthma patients
      may consist of two functionally distinct subpopulations: those which up-regulate
      (pro-allergic) and those which down-regulate (anti-allergic) the allergic release
      of mediators from mast cells and basophils.

PMID- 7516816
TI  - Induction of a low voltage-activated, fast-inactivating Ca2+ channel in cultured
      bone marrow stromal cells by dexamethasone.
AB  - The production of biochemical markers associated with the osteoblastic phenotype,
      and accompanying changes in the expression of voltage-operated Ca2+ channels,
      have been examined in rat bone marrow stromal cell cultures treated with
      dexamethasone (10(-8) M). Whole cell clamp analysis of voltage-operated Ca2+
      channels in control cultures (using Ba2+ as the charge carrier) revealed
      primarily a high voltage-activated (HVA), slowly inactivating current, which was
      enhanced two- to threefold by treatment of the cells with Bay K 8644 (300 nM) and
      inhibited by nifedipine (4 microM). In dexamethasone-treated cultures, the I-V
      relationship for inward current was shifted to more positive potentials in
      comparison with control cells. Most cells in these cultures possessed both the
      HVA current and also a faster inactivating, low-voltage-activated (LVA),
      nifedipine-resistant current. These two currents could be separated both by
      nifedipine and by the use of steady state inactivation of the LVA current. The
      two components of the Ba2+ current varied widely in their relative size. The
      combination of LVA and HVA currents seen in dex-induced stromal cells resembles
      records of voltage-operated Ca2+ channels from cultures of calvarial osteoblasts.

PMID- 7516817
TI  - Effects of lead on osteoclast-like cell formation in mouse bone marrow cell
      cultures.
AB  - To examine an effect of lead (Pb) on the process of osteoclast-like cell
      formation from its progenitors, we used a mouse bone marrow culture system in
      which osteoclast-like multinucleated cells (MNCs) were formed in response to bone
      resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC
      formation over the concentration range 2-10 microM, whereas at 40 microM Pb, MNC
      formation declined. In an 11-day culture period, MNC formation reached a maximum
      at 5 microM Pb and decreased with increasing concentration of Pb at 10-40 microM.
      Pb-stimulated MNC formation was inhibited by both indomethacin and SC19220, an
      antagonist of prostaglandin E2 (PGE2) receptor. Pb stimulated the production of
      PGE2 in marrow cell cultures, suggesting that Pb-stimulated MNC formation is
      dependent on the production of PGE2. 3-Isobutyl-1-methylxanthine potentiated Pb
      stimulated MNC formation and 2',5'-dideoxyadenosine, an inhibitor of adenylate
      cyclase, inhibited it. A calcium ionophore A23187 increased Pb-induced MNC
      formation and verapamil, a calcium channel blocker, depressed it. It is possible
      that a PGE2-induced increase in the levels of cyclic adenosine 3',5'
      monophosphate (cAMP) and calcium ions in marrow cells is involved in Pb-induced
      MNC formation. Pb and parathyroid hormone showed a synergistic stimulation on MNC
      formation. From these results, Pb is thought to induce osteoclast-like cell
      formation by a mechanism involving PGE2 which increases the intracellular levels
      of cAMP and calcium ions.

PMID- 7516818
TI  - Canine colonic circular muscle generates action potentials without the pacemaker
      component.
AB  - Two dominant types of action potentials in canine colon are slow wave type action
      potentials (slow waves) and spike-like action potentials (SLAPs). The slow waves,
      originating at the submuscular surface where a network of interstitial cells of
      Cajal (ICCs) is found, possess a pacemaker component. Activation of the pacemaker
      component is insensitive to voltage changes and L-type calcium channel blockers,
      and is postulated to involve a metabolic clock sensitive to cyclic AMP. SLAPs are
      more prominent in the longitudinal muscle. To understand the contribution
      circular muscle cells make to the generation of these action potentials, a
      circular muscle preparation (devoid of the submuscular ICC-smooth muscle network,
      longitudinal muscle, and myenteric plexus) was developed. Circular muscle
      preparations were spontaneously quiescent, with a resting membrane potential of 
      62.9 +/- 0.6 mV. Ba2+ (0.5 mM) depolarized the cells to -51.8 +/- 0.6 mV and
      induced electrical oscillations with a frequency, duration, amplitude, and rate
      of rise equal to 6.6 +/- 0.4 cpm, 2.2 +/- 0.2 s, 19.4 +/- 0.9 mV, and 21.8 +/-
      1.7 mV/s, respectively. In most cases, Ba(2+)-induced oscillations were preceded
      by a prepotential of 4.4 +/- 0.3 mV, with a rate of rise of 1.1 +/- 0.1 mV/s.
      Ba(2+)-induced oscillations were abolished by 1 microM D600 as well as by
      repolarization of 6-12 mV. Addition of 0.1 microM Bay K8644 in the presence of
      Ba2+ further depolarized circular muscle cells to -42.4 +/- 0.8 mV and increased
      the oscillation frequency to 16.8 +/- 1.8 cpm. The electrical oscillations
      induced in circular muscle preparations by Ba2+ and Bay K8644 were similar to the
      SLAPs exhibited by the isolated longitudinal muscle layer, indicating that
      generation of SLAPs is an intrinsic property of smooth muscle cells. Forskolin (1
      microM), previously shown to dramatically decrease the frequency but not the
      amplitude of slow waves in preparations including the submuscular ICC network,
      decreased the amplitude of the Ba(2+)-induced oscillations in circular muscle
      preparations without changing the frequency. These results provide strong
      evidence for the hypothesis that the submuscular ICC-smooth muscle network is
      essential for the initiation of the pacemaker component of the colonic slow
      waves. The mechanism for regulating the frequency of slow waves is different from
      that responsible for the Ba(2+)-induced oscillations in circular muscle
      preparations. Circular muscle cells are shown to be excitable and capable of
      generating oscillatory activity dominated by L-type calcium channel activity,
      which is regulated by K+ conductance.

PMID- 7516820
TI  - In vivo radiation protection by nitric oxide modulation.
AB  - Drugs that affect blood flow have been shown to be whole body radiation
      protectors. Using NG-nitro-L-arginine, a specific inhibitor of nitric oxide
      synthase, and the NO-releasing agent (C2H5)2N[N(O)NO-]Na+ (DEA/NO), we have
      studied the ability of NO to modulate whole body radiation toxicity in C3H mice.
      NG-Nitro-L-arginine given to mice between 15 and 60 min prior to radiation
      afforded significant protection from whole body irradiation, e.g., the estimated
      whole body irradiation dose required to kill 50% of mice by 30 days after
      radiation (LD50/30) in mice treated with NG-nitro-L-arginine 60 min before
      irradiation was 1051 cGy compared with a whole body radiation LD50/30 of 822 cGy
      in control mice (P < 0.00001). Treatment of mice with DEA/NO prior to whole body
      irradiation also significantly reduced toxicity; the estimated whole body
      radiation LD50/30 was 1063 and 945 cGy in mice treated with DEA/NO 10 or 30 min
      before irradiation, respectively (P < 0.00001 for radiation LD50/30 of either
      DEA/NO-treated group compared with control). Measurement of [14C]etanidazole
      binding to bone marrow demonstrated that DEA/NO and NG-nitro-L-arginine
      exacerbated bone marrow hypoxia. Perturbations of NO levels have profound effects
      on in vivo radiosensitivity of normal tissues. We hypothesize that alterations in
      regional blood flow may underlie the changes in radiosensitivity that we have
      observed.

PMID- 7516819
TI  - Surface protein expression and messenger RNA-splicing analysis of CD44 in uterine
      cervical cancer and normal cervical epithelium.
AB  - Variant CD44 has recently been shown to serve as a metastasis marker in human
      breast cancer. Certain variant epitopes on primary tumors predict poor survival
      probabilities for the patients. In this study, immunohistochemical analysis of 16
      uterine cervical carcinomas showed strong expression of several CD44 variant
      epitopes in all samples. In normal cervical epithelia from 5 patients, expression
      of these epitopes was restricted to particular cell layers, with expression being
      strong in basal and spinal cells but absent in superficial cells. Fifteen of 16
      cancer samples were stained strongly with an antibody which recognizes one
      particular CD44 epitope that is encoded by both variant exons v7 and v8. This
      epitope was not detectable in normal cervical epithelium. CD44-mRNA splicing
      analysis showed qualitative and quantitative differences between malignant and
      normal tissues with a much more complex splice pattern and high expression of a
      large CD44 isoform containing variant exons v3 to v10 (including the v7/v8
      transition epitope) in about one-half of the cancer samples. Interestingly,
      patients with lymph node metastases were in this group only. These differences in
      CD44 epitope expression and mRNA splicing in cervical carcinoma reveal dynamic
      changes in CD44 expression during carcinogenesis. Such changes could provide
      metastatic cells with a selective advantage during the carcinogenic process.
      Furthermore, the v7/v8 epitope may be suitable for screening early stages of
      cervical cancer.

PMID- 7516821
TI  - Effect of isotype on internalization and cytotoxicity of CD19-ricin A
      immunotoxins.
AB  - We analyzed the effect of isotype variation on effectiveness of B-cell CD19
      immunotoxins (IT) by using class switch variants (CLB-B4-IgG1 and CLB-B4-IgG2a)
      conjugated to ricin A. Notably, IgG1-IT appeared to be approximately 100-fold
      more potent than IgG2a-IT toward B-cell lines Daudi and KM3. Binding and
      internalization studies with 125I-labeled monoclonal antibodies (mAbs) revealed a
      higher cellular uptake of IgG1 compared to IgG2a, despite similar binding
      affinities. Following removal of the Fc part, both mAbs internalized at the same
      rate as IgG2a, indicating that the Fc part of IgG1 is involved in enhanced
      cellular uptake. The involvement of Fc gamma RII (CD32) in this process was
      demonstrated by a decreased cytotoxicity of IgG1-IT (and not IgG2a-IT) in the
      presence of Fc gamma RII-blocking mAbs AT10 or IV.3. To identify the isoform
      responsible for this phenomenon, internalization of IgG1 and IgG2a in 11 B-cell
      lines and malignant B-cells of 8 patients was compared with expression of Fc
      gamma RII subclasses. In addition to four cell lines (Daudi, KM3, Nalm6, and
      Raji), the malignant B-cells of two patients showed enhanced uptake of IgG1
      relative to IgG2a. Only the Fc gamma RIIa transcript was found in all B-cells.
      Furthermore, enhanced uptake of IgG1 correlated with rosetting of erythrocytes
      sensitized with anti-glycophorin A mAb of IgG1 isotype rather than with Fc gamma
      RIIa membrane expression levels. These data support the idea that functional Fc
      gamma RIIa is involved in the enhanced IgG1 uptake observed in a subset of B
      cells. Our study, therefore, points to an important role for the Fc region of IT
      in the delivery of cytotoxic effects.

PMID- 7516822
TI  - Effects of neuropeptide analogues on calcium flux and proliferation in lung
      cancer cell lines.
AB  - Small cell lung cancers (SCLC) and some non-small cell lung cancers (NSCLC) have
      neuroendocrine features which include production of a variety of neuropeptides,
      cell surface expression of the receptors for these peptides, and autocrine
      stimulation by the peptides. Previous studies showed that some peptide
      antagonists and anti-peptide antibodies inhibited the growth of SCLC cell lines
      which expressed receptors for the specific peptide. We and others showed that the
      heterogeneity of peptide receptor expression and responsiveness was a major
      potential obstacle for developing therapeutic uses of peptide antagonists. In
      this manuscript we evaluated the effects of 11 peptide antagonists (3 bombesin
      specific, 2 cholecystokinin-specific, 1 arginine vasopressin (AVP)-specific, and
      5 substance P derivatives with broad specificity) on peptide-induced calcium
      mobilization and growth of SCLC and NSCLC cell lines. For each antagonist, we
      determined the dose-response effects, specificity of peptide antagonism, and
      biological stability in serum using Indo-1AM-based flow cytometric assays. We
      found that the three bombesin antagonists, S30, SC196, and L336,175, varied in
      potency from 10 nM to 10 microM, varied in serum stability from 6 h to more than
      24 h, and had no effect on the calcium response elicited by other peptides. None
      of these compounds effectively inhibited the growth of SCLC cell lines in
      [3H]dThd and cell growth assays in vitro. Similarly, the three cholecystokinin
      and AVP antagonists were highly specific for cholecystokinin and AVP,
      respectively, had widely varying potency, but had little inhibitory effect on
      SCLC growth in vitro. In contrast, the five substance P derivatives inhibited the
      calcium response to bombesin, AVP, bradykinin, and fetal bovine serum. None of
      these five antagonists were as potent as the six specific antagonists described
      above, but they were more effective in inhibiting the growth of SCLC cell lines
      in vitro. These substance P derivatives inhibited the growth of peptide-sensitive
      SCLC cell lines more efficiently than their inhibition of peptide-insensitive
      NSCLC or breast cancer cell lines. Relatively high concentrations of these
      substance P derivatives were required to inhibit in vitro growth, even in the
      absence of added peptide. It is likely that more potent broad spectrum
      antagonists, toxins, or radiolabeled stable antagonists will need to be developed
      for maximal clinical development of this type of anti-growth factor therapy.

PMID- 7516823
TI  - Structural studies of the O-polysaccharide from the lipopolysaccharide of
      Moraxella (Branhamella) catarrhalis serotype A (strain ATCC 25238).
AB  - The polysaccharide of the Moraxella (Branhamella) catarrhalis serotype A
      lipopolysaccharide was prepared by mild acid hydrolysis followed by gel
      permeation chromatography. The structure was established by methylation analysis,
      mass spectrometry, and NMR spectroscopy. It is concluded that the O-antigenic
      polysaccharide has the following structure. [formula see text] Methylation
      analysis of the intact lipopolysaccharide showed that the lipid A portion
      consisted of 6-substituted glucosamine residues. Methylation followed by
      methanolysis showed that two Kdo residues were present, one terminal and one 4,5
      substituted residue. A terminal Kdo thus substitutes the branch-point Kdo in the
      4-position.

PMID- 7516824
TI  - Differential scanning calorimetry study on the binding of nucleic acids to
      dimyristoylphosphatidylcholine-sphingosine liposomes.
AB  - Binding of DNA and RNA to sphingosine-containing dimyristoylphosphatidylcholine
      (DMPC) liposomes was characterized by differential scanning calorimetry. The
      thermal phase behaviour of neat DMPC liposomes was unaffected by the presence of
      the nucleic acids. However, significant alterations in the melting profiles of
      the DMPC/sphingosine composite membranes were produced by DNA and RNA, thus
      revealing their binding to the liposomes. For example, for 79:21 (molar ratio)
      DMPC/sphingosine liposomes a single endotherm at 29.1 degrees C with an enthalpy
      of 6.3 kcal/mol lipid was observed. In the presence of DNA at the
      nucleotide/sphingosine ratio of 0.6 this endotherm separated into three distinct
      peaks at 28.0, 31.4 and 35.1 degrees C, together with an approximately 22%
      reduction in the total enthalpy. Further increase in DNA concentration up to 1.5
      nucleotides per sphingosine led to complete loss of the original heat absorption
      peak of the DMPC/sphingosine liposomes, while an endotherm at 34.3 degrees C with
      delta H of 2.7 kcal/mol developed. By visual inspection, rapid and extensive
      aggregation of the liposomes due to DNA was evident. Evidence for DNA-induced
      phase separation was also provided by compression isotherms of sphingosine
      containing DMPC monolayers recorded over an aqueous buffer both in the presence
      and absence of DNA. The effects of RNA on the thermal phase behaviour of the
      composite liposomes were qualitatively similar to those described above for DNA.
      Notably, the presence of eggPA abolished the nucleic acid induced heat capacity
      changes for DMPC/sphingosine liposomes probably because of neutralization of the
      positive charge of sphingosine. The binding of DNA to DMPC/sphingosine liposomes
      occurred both below and above the lipid phase transition temperature, as shown by
      fluorescence resonance energy transfer utilizing adriamycin-labelled DNA as a
      quencher and membrane incorporated pyrene-labelled phospholipid as a donor.
      However, the apparent binding to liquid crystalline liposomes was slightly more
      effective.

PMID- 7516825
TI  - Modification of vasopressin microvascular responses by endotoxin, endothelin, and
      nitric oxide.
AB  - The sensitivity of rat cremaster muscle arterioles to topically applied arginine
      vasopressin (AVP) is greatly increased by endotoxin (ENDT) [1]. The hypothesis is
      that the increase in vasoconstrictor sensitivity is in part due to modification
      of the AVP responses by endothelial compounds such as nitric oxide (NO) and
      endothelin. Reactivity of left cremaster muscle microvessels of pentobarbital
      anesthetized Sprague-Dawley rats was measured using videomicroscopy. Femoral
      arterial pressure as well as second and third order arteriolar (A2 and A3)
      vasoconstrictor threshold responses were determined for topical AVP (10(-15)-10(
      6) M). These measurements were repeated in the presence of ENDT (6 mg/kg) alone
      and in the presence of the NO synthase inhibitor L-NAME (N omega-nitro-L-arginine
      methyl ester; 1 mg/kg) and ENDT (group 1). The control threshold (M)(-log) for
      arteriolar constriction by AVP was 9.4 +/- 0.7. After ENDT the threshold
      decreased significantly (P < 0.05) to 13.8 +/- 0.5, but returned to 9.0 +/- 0.5
      after i.v. injected L-NAME. Acetylcholine (ACh) injected i.a. during AVP
      constriction significantly increased diameters at control and after ENDT, but not
      after L-NAME. In group 2 the AVP threshold was determined at control, after L
      NAME plus hydroquinone (HQ), and at 30, 90, and 120 min post-ENDT in the presence
      of L-NAME + HQ. The AVP threshold at control was 9.0 +/- 0.3, after L-NAME 9.0 +/
      0.6, and after HQ 8.0 +/- 0.7. After L-NAME + HQ, the threshold was
      significantly increased to 7.3 +/- 0.2. After ENDT, in the presence of both
      antagonists, the threshold remained elevated at 7.4 +/- 0.2.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7516826
TI  - Two independent sets of monoclonal antibodies define neoepitopes linked to
      soluble ligand binding and leukocyte adhesion functions of activated alpha M beta
      2.
AB  - The integrin alpha M beta 2 mediates a variety of events, adhesive, phagocytic,
      and inflammatory. Evidence has suggested that the functional events may be
      mediated by the "activated" conformational forms of alpha M beta 2 produced by
      appropriate stimulation of myeloid and monocytic lineage. The activation of alpha
      M beta 2 may be associated with new epitopes on alpha M beta 2, sites that may be
      related to the acquired receptor functions. Monoclonal antibodies were produced
      that preferentially bind neoepitopes expressed by activated alpha M beta 2. These
      anti-neo antibodies each inhibited three activation-associated specific receptor
      alpha M beta 2 functions, though to different extents. One set of anti-neo
      antibodies inhibited in a concordant manner the binding of factor X and of
      fibrinogen by > 90%, abolished the alpha M beta 2-initiated cellular coagulant
      response, and inhibited monocyte adhesion to unstimulated endothelial monolayers.
      A second set of anti-neo antibodies only diminished factor X and fibrinogen
      binding by approximately 40% to 50% but markedly suppressed Xa generation and
      only partially inhibited monocyte adherence to unstimulated endothelium.
      Concordance was observed between binding of factor X or fibrinogen and competence
      for leukocyte adhesion to unstimulated endothelium. Antibody competition assays
      segregated the anti-neo antibodies into the same two distinct sets, consistent
      with recognition of separate neoepitopes that are linked to alpha M beta 2
      function. These data support the conclusion that the activated conformer of alpha
      M beta 2 that binds fibrinogen and factor X also mediates monocyte-endothelial
      interactions as well as the alternative cellular coagulation pathway.

PMID- 7516827
TI  - Acute cholinergic blockade with low dose pirenzepine reduces the insulin and
      glucose responses to a mixed meal in obese women with the polycystic ovary
      syndrome.
AB  - OBJECTIVES: Pirenzepine, a selective muscarinic cholinergic antagonist, reduces
      plasma insulin and plasma glucose responses to a mixed meal in a dose dependent
      fashion in normals and in patients with non-insulin dependent diabetes. We have
      studied the effects of pirenzepine on plasma insulin, plasma glucose, growth
      hormone (GH), androstenedione, testosterone, insulin-like growth factor-I (IGF-I)
      and IGF binding protein 1 (IGFBP-1) responses to a mixed meal in obese clinically
      hyperandrogenic women with the polycystic ovary syndrome. SUBJECTS AND METHODS:
      Six obese women with polycystic ovary syndrome (BMI range 27.3-39.8 kg/m2) were
      studied in random sequence, and received either placebo or pirenzepine (single
      doses of 50, 100, or 200 mg) one hour before a standard test meal. Blood was
      sampled every 15 minutes for 2 hours after the meal and every 30 minutes
      thereafter for a total of 4 hours. RESULTS: Mean fasting plasma insulin
      concentrations were increased. Peak post-prandial plasma insulin concentrations
      were reduced significantly by all three doses used. Post-prandial integrated
      plasma insulin concentrations were reduced by the two higher doses. Peak post
      prandial plasma glucose concentrations were also reduced. The late post-prandial
      GH surge was significantly suppressed by all three doses. However, plasma
      androstenedione, testosterone, IGF-I and IGFBP-1 concentrations were not
      significantly different when placebo was compared with pirenzepine 200 mg.
      CONCLUSIONS: Acute cholinergic muscarinic blockade with pirenzepine significantly
      reduces meal stimulated plasma insulin and plasma glucose concentrations in
      clinically hyperandrogenic women with polycystic ovary syndrome. The ability of
      pirenzepine to reduce plasma insulin without worsening glycaemia is a particular
      advantage and may be therapeutically relevant. Further studies are under way to
      assess the usefulness of pirenzepine in long-term suppression of plasma insulin
      in this group of patients.

PMID- 7516829
TI  - Characterization and measurement of prostate-specific antigen using monoclonal
      antibodies.
AB  - Monoclonal and polyclonal antibodies were produced using a pure preparation of
      prostate-specific antigen (PSA) as determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). By SDS-PAGE, the apparent
      molecular weight of PSA was about 33 kD. Eighty-four monoclonal antibodies were
      produced, 77 of which bind PSA with an affinity higher than 10(9) M-1. Use of
      these monoclonal antibodies to study the immunological characteristics of PSA
      revealed the presence of 4 epitopes. Injection of PSA into goats resulted in a
      production of polyclonal antibodies with high affinity. These polyclonal
      antibodies were purified by affinity chromatography and adsorbed on plastic
      tubes. By an immunometric assay, we have also demonstrated that polyclonal
      antibodies bind PSA at a fifth epitope that is different from those of monoclonal
      antibodies. Using an iodinated monoclonal antibody and polyclonal antibodies
      adsorbed on plastic tubes, a sensitive immunoradiometric assay could be
      developed, and a further increase in sensitivity could be achieved by using a
      mixture of 2 monoclonal antibodies. The serum PSA levels in 2,250 patients
      measured with this immunoradiometric assay were identical to the values
      determined by Tandem-R, although the present assay reached a minimum detectable
      value of 0.05 ng/ml compared with 0.2 ng/ml by Tandem-R.

PMID- 7516828
TI  - Biochemical markers of bone turnover in girls during puberty.
AB  - OBJECTIVE: Bone turnover and the rate of bone growth increase dramatically during
      puberty. A number of new assays for the estimation of bone resorption and
      formation rates have been developed over recent years, and puberty acts as a
      convenient model for evaluation of these measurements. The aim of this study was
      to explore the interrelationships between pubertal development, biochemical
      markers of bone turnover, insulin-like growth factor I and oestradiol in healthy
      pubertal girls. SUBJECTS: Ninety-one healthy girls (ages 11.6-15.5 years) were
      studied. All subjects were apparently healthy, and were not taking medications
      known to influence calcium homeostasis. Breast examination was performed to
      assess pubertal stage according to Tanner. The adult reference range for
      biochemical markers of bone turnover was obtained from concurrent studies on 42
      healthy premenopausal women ranging in age between 20 and 45 years. DESIGN AND
      MEASUREMENTS: Blood samples were obtained from subjects between 0800 and 1000 h.
      Urine samples were collected between 1330 and 1600 h. We measured total and bone
      specific alkaline phosphatase, osteocalcin, and type I procollagen
      carboxyterminal propeptide as markers of bone formation. Tartrate resistant acid
      phosphatase, carboxyterminal pyridinoline cross-linked telopeptide, creatinine
      corrected urinary deoxypyridinoline, immunoreactive urinary pyridinolines, and
      urinary galactosyl hydroxylysine were measured as markers of bone resorption.
      RESULTS: Bone turnover as reflected by each of the markers was maximal in mid
      puberty (breast Tanner stages II and III) and decreased towards adult levels in
      late puberty (P < 0.001). However, the magnitude of the mid-pubertal increase
      differed between markers. In particular, the pubertal increase in levels of bone
      specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline were
      higher than the increase shown by the other markers. All markers were
      significantly lower after the menarche. Circulating insulin-like growth factor I
      and insulin like growth factor binding protein-3 were not important determinants
      of pubertal changes in bone turnover. In contrast, there was a significant
      negative correlation between oestradiol and all markers of bone formation and
      resorption during puberty. CONCLUSIONS: The greater pubertal increase in levels
      of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline
      suggests that these markers may be relatively more sensitive as indicators of
      skeletal health during puberty. The differences between markers may reflect
      differences in the bone specificity of the analytes, or differing mechanisms of
      production and clearance. The negative correlation between oestradiol and markers
      of bone resorption and formation suggests that this hormone may be responsible
      for the reduction in bone turnover in late puberty.

PMID- 7516830
TI  - Issues on standardization of immunoassays for prostate-specific antigen: a
      review.
AB  - The proposed use of serum prostate-specific antigen (PSA) for annual screening of
      men over age 50 will require careful standardization of the various commercial
      immunoassays to allow year-to-year comparisons for individual patients. Some
      current PSA assays give significantly different results on testing the same
      sample. The standardization process will require several steps. First, a primary
      antigen standard should be purified from seminal plasma (a convenient source),
      using a reproducible technique. The modified Sensabaugh-Blake purification of PSA
      yields a suitable pure antigen. Next, PSA values need to be assigned to PSA
      containing serum samples. These secondary serum-based reference materials can be
      used by manufacturers and regulatory agencies to develop and monitor the
      performance of PSA assays. In serum, 2 forms of PSA are detected immunologically:
      a free form (M(r) = 30 kD) and a form complexed with alpha-1-antichymotrypsin
      (M(r) = 100 kD). Different immunoassays for PSA detect these 2 forms in different
      molar ratios. The most promising approach to this problem is to select a
      reference immunoassay that detects both forms of PSA in equal molar ratios. A
      series of samples containing various and known levels of naturally occurring
      serum PSA can then serve as secondary serum-based reference materials for
      calibration of other commercial PSA immunoassays. Equimolar standardization is a
      useful method for any set of assays that detect free and bound forms of a ligand
      in differing molar ratios. The technical simplicity and power of this approach
      should allow early agreement on standardization of PSA immunoassays and will
      greatly assist PSA screening programs for prostate cancer now in progress.

PMID- 7516831
TI  - Optimized strategy for detection of early stage, curable prostate cancer: role of
      prescreening with prostate-specific antigen.
AB  - In 1,002 men aged 45-80 y, 81% of the cancers detectable by serum prostate
      specific antigen (PSA), digital rectal examination (DRE), and transrectal
      ultrasonography (TRUS) were present in a subpopulation (19% of total) identified
      by serum PSA above the threshold value of 3.0 micrograms/L. This study was
      extended to 7,350 men using serum PSA and DRE as first approach, followed by TRUS
      only when 1 of these 2 tests was abnormal. Because the aim of prostate cancer
      detection is to find cancers at an early, potentially curable stage, it is of
      major interest that 71.8% of evaluable cancers were clinical stage B; 8.4% and
      10.7% were stages C1 and C2, respectively; only 9.2% were stage D (metastatic) at
      first visit while none was at stage D at follow-up visits. This study, the first
      performed in an unselected, unscreened population, shows that serum PSA is the
      most sensitive technique to identify men at high risk of having prostate cancer
      and that 12% more cancers can be found at first visit by doing DRE in addition to
      PSA. Follow-ups can be done every second year using serum PSA alone, as 97% of
      the cancers detected at annual follow-up by DRE + PSA were PSA+. Cancers are
      discovered by the present approach at an estimated cost of $2,665 per cancer.
      Such cancers are potentially curable in at least 80% of cases detected at first
      visit and in 97% of cases at follow-up. This strategy offers the possibility to
      improve markedly morbidity and mortality from prostate cancer, presently the
      second leading cause of cancer death in North American men.

PMID- 7516832
TI  - Early detection of prostate cancer following repeated examinations by multiple
      modalities: results of the American Cancer Society National Prostate Cancer
      Detection Project.
AB  - The American Cancer Society National Prostate Cancer Detection Project (ACS
      NPCDP) is a multicenter, interdisciplinary demonstration project to assess the
      impact on early detection of transrectal ultrasound (TRUS), prostate-specific
      antigen (PSA), and digital rectal examination (DRE). Preliminary data are
      available from the first 3-5 y of planned observation. The results show declining
      rates of detection for each succeeding examination. Cancer detection rates are
      highly dependent on age. The positive predictive value of a solitary examination
      is low regardless of modality, but any combination of positive results has a much
      better predictive value. The cancers detected were predominantly clinically
      localized tumors, and detection of advanced stage cancer was uncommon after the
      initial examination. Radical prostatectomy was the most common form of treatment.
      These findings have implications for prostate cancer early detection guidelines
      and practice.

PMID- 7516833
TI  - Prostate Cancer Awareness Week, 1992: a summary of key findings.
AB  - Prostate Cancer Awareness Week was begun in 1989 to investigate whether men could
      be recruited to participate in free prostate cancer screening. Initially designed
      to raise public awareness of "the ignored male disease", it has become the
      largest single cancer screening program in the United States. In 1992, more than
      500,000 men were examined by digital rectal examination (DRE) and more than half
      of these also by measuring prostate-specific antigen (PSA). Although the
      populations examined have been generally better educated than the national
      average, predominantly white, and typically (> 40%) experiencing some symptom of
      prostate disease, adherence to annual prostate examinations remains low among
      successive cohorts of participants. Prostate cancers detected through this
      program exhibit a more favorable stage distribution than the national average.
      From 1989 through 1992, many cancers were detected by using the effective
      combination of DRE and PSA testing, which resulted in more stage A disease being
      diagnosed and fewer stage B, C, and D tumors. Data from 1992 suggest that
      increasing sophistication is possible with PSA test results, and age-specific PSA
      reference ranges have been developed.

PMID- 7516834
TI  - Prostate-specific antigen and transrectal ultrasound of the prostate in detection
      of prostate cancer.
AB  - Detection of prostate cancer can be enhanced over the level historically obtained
      by digital rectal examination through the combined use of serum prostate-specific
      antigen and digital rectal examination, followed by transrectal ultrasonic
      examination of the prostate and ultrasonically guided biopsy if either of the
      initial studies is abnormal. Use of age-specific reference ranges for prostate
      specific antigen results in greater sensitivity of this serum marker in patients
      below the age of 60 y and greater specificity in older patients.

PMID- 7516835
TI  - Neoadjuvant hormonal therapy in stage C adenocarcinoma of the prostate.
AB  - This report describes the effects of neoadjuvant hormonal therapy on 16 patients
      (mean age = 65 y) with clinical stage C adenocarcinoma of the prostate (CaP) who
      underwent radical prostatectomy from December 1991 to June 1993 at the University
      of Colorado Health Sciences Center. Staging of CaP was determined by digital
      rectal exam, transrectal ultrasonography (TRUS), radionuclide bone scanning,
      abdominal and pelvic computed tomography scanning, transrectal coil magnetic
      resonance imaging, and serum acid phosphatase. Most patients underwent a
      laparoscopic lymph node dissection to rule out micrometastasis. Every patient was
      treated for 4 months with a combination of a gonadotrophin-releasing hormone
      (GnRH) agonist (Lupron) and an anti-androgen (flutamide, Eulexin). Serial
      prostate-specific antigen (PSA) levels, post-treatment prostate volume measured
      by TRUS, and whole-mount sectioning of the surgical specimen were studied. The
      PSA levels decreased from a mean of 39.1 ng/ml (Hybritech method) to a mean of
      0.43 ng/ml; (p < 0.0001). Prostate volumes in all patients demonstrated a mean
      decrease of 52% (p < 0.0001), and pathological effects of hormonal deprivation
      were observed in all patients. By whole-mount sectioning of the radical
      prostatectomy specimens, 3 patients had organ-confined disease (stage B), 6
      showed invasion of the capsule with surgical margins free of tumor (stage C1), 3
      had extracapsular extension with positive surgical margins (stage C2), and 4 had
      extracapsular extension with seminal vesicle involvement (stage C3). We conclude
      that by downsizing and markedly decreasing serum PSA values, neoadjuvant hormonal
      therapy offers an alternative treatment for stage C carcinoma of the
      prostate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516838
TI  - Conflicting duties: plague and the obligations of early modern physicians towards
      patients and commonwealth in England and The Netherlands.

PMID- 7516837
TI  - Beyond the Hippocratic Oath.

PMID- 7516836
TI  - Neoadjuvant hormonal deprivation before radical prostatectomy.
AB  - Hormonal deprivation by combination therapy before radical prostatectomy has been
      recently introduced. The main purpose of such treatment is to achieve
      downstaging, downgrading, improvement of surgical results, and prolonged
      survival. Our experience with the last 100 patients who underwent radical
      prostatectomy at our hospital, of whom 40 received complete androgen blockade
      (luteinizing hormone-releasing hormone (LHRH) superagonist and flutamide) before
      radical surgery, has shown a definitive decrease in prostatic volume of 40-50%.
      Of these 40 patients, 25 were clinical stage T2 and 15 stage T3 at diagnosis. The
      reduction in volume facilitates dissection of the prostate from close vulnerable
      structures, resulting in reduced blood loss and operating time. Also, return of
      urinary continence is more rapid. Combination therapy resulted in clinical
      downstaging in one third of the patients; at histopathology, upstaging occurred
      in 12.5% (5 of 40) of patients, compared with the expected 30-50% upstaging in
      patients untreated before surgery. Serum prostate specific antigen (PSA) dropped
      to undetectable levels in 59% of the patients 3 months after hormonal
      suppression. Among these, 80% had PT2, and only 13% had PT3, tumor; one patient
      had a PT0 tumor. On the other hand, all patients who still had PSA > 4 ng/ml
      after neoadjuvant combination therapy had stage PT3-PT4 disease. Histological
      changes were observed in both the non-neoplastic tissue and the prostatic
      carcinoma, with more marked effects in the latter. The surgical margins were
      positive in 32% of the treated patients, compared with 57% in the control
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516839
TI  - Ethics in the eighteenth century: Hoffmann in Halle.

PMID- 7516841
TI  - The ethical discourse on animal experimentation, 1650-1900.

PMID- 7516840
TI  - Infanticide and medico-legal ethics in eighteenth century Prussia.

PMID- 7516842
TI  - Thomas Gisborne: physicians, Christians and gentlemen.

PMID- 7516843
TI  - Does a certificate of lunacy affect a patient's ethical status? Psychiatric
      paternalism and its critics in Victorian England.

PMID- 7516844
TI  - Medical ethics in transition in the Latin medicine of the thirteenth and
      fourteenth centuries: new perspectives on the physician-patient relationship and
      the doctor's fee.

PMID- 7516845
TI  - The medical ethics of Gabriele de Zerbi.

PMID- 7516846
TI  - Medical ethics in early modern England.

PMID- 7516847
TI  - Children and poverty: issues in contemporary research.
AB  - The state-of-the-art research in this volume is based on complex,
      multidimensional conceptions of poverty. Current research goes beyond description
      to emphasize analysis of processes by which effects occur and variations in
      effects associated with race, gender, and ethnicity. Child care, school,
      neighborhood, and community are studied as well as family contexts. The child
      outcomes investigated include both intellectual development and socioemotional
      functioning. It is multidisciplinary, using a broad range of analytic frameworks
      and research methods from economics, sociology, health, psychology, and other
      disciplines. In this introduction, the overall research trends are described, and
      new questions for future research are identified.

PMID- 7516848
TI  - Poverty and child development: relevance of research in developing countries to
      the United States.
AB  - Data from low-income countries are helpful in understanding the effects of
      poverty on child development in the U.S. Illustrative are 3 public health issues:
      (1) In the U.S., among poor African-American and Hispanic babies anemia is as
      high as 20%-24%, while in low-income countries, iron deficiency anemia (IDA)
      causes poor performance on mental and motor tests among babies and children.
      These data suggest that IDA is a major public health problem among poor minority
      children that requires prompt attention. (2) In 1993 the U.S. government
      appropriated $2.86 billion for the Special Supplemental Food Program for Women,
      Infants, and Children (WIC). Evaluations of WIC, however, have failed to yield
      conclusive information on the benefits of the program. In low-income countries,
      nutritional supplements targeted to at-risk groups have resulted in developmental
      benefits. Thus, WIC is likely to buffer intellectual development against the
      adverse effects of malnutrition observed among poor children. (3) Evidence from
      developing countries suggests that concurrent illnesses and poor nutrition
      interfere with schooling. However, in the U.S., attention to such issues has
      declined, while common illnesses have increased among the poor. A reappraisal of
      this issue is warranted to meet the education and health goals proposed for the
      year 2000 in the U.S.

PMID- 7516850
TI  - Role of the insulin-like growth factors in the endocrine control of glucose
      homeostasis.
AB  - There is a growing body of evidence that the insulin-like growth factors (IGF-I
      and IGF-II) are dynamically involved in the regulation of glucose homeostasis,
      with one of their binding proteins, IGFBP-1, playing a counterregulatory role.
      The IGFs are structurally and functionally related to insulin and in the
      circulation they represent a huge hypoglycemic potential which is buffered by
      their association with the IGFBPs. The predominant IGFBP in serum, IGFBP-3, is
      able to form a high molecular weight complex with the IGFs and this complex is
      retained in the circulation and appears to act as a reservoir of IGFs. The IGFs
      and IGFBP-3 are regulated in the long term by changes in nutritional status. In
      contrast, IGFBP-1 is acutely regulated in a manner similar to glucose
      counterregulatory hormones. IGFBP-1 is able to block the insulin-like actions of
      the circulating IGFs and when administered alone as a bolus infusion causes an
      increase in blood glucose levels. There is recent evidence that more IGFs are
      available for an endocrine glucoregulatory role than indicated by estimates of
      steady-state 'free' IGF levels. The IGF/IGFBP system may thus play a
      complementary role to insulin and the classical counterregulatory hormones in the
      control of blood glucose.

PMID- 7516849
TI  - Economic deprivation and early childhood development.
AB  - We consider 3 questions regarding the effects of economic deprivation on child
      development. First, how are developmental outcomes in childhood affected by
      poverty and such poverty correlates as single parenthood, ethnicity, and maternal
      education? Second, what are the developmental consequences of the duration and
      timing of family economic deprivation? And, third, what is the comparative
      influence of economic deprivation at the family and neighborhood level? We
      investigate these issues with longitudinal data from the Infant Health and
      Development Program. We find that family income and poverty status are powerful
      correlates of the cognitive development and behavior of children, even after
      accounting for other differences--in particular family structure and maternal
      schooling--between low- and high-income families. While the duration of poverty
      matters, its timing in early childhood does not. Age-5 IQs are found to be higher
      in neighborhoods with greater concentrations of affluent neighbors, while the
      prevalence of low-income neighbors appears to increase the incidence of
      externalizing behavior problems.

PMID- 7516851
TI  - Cytotoxic activity in children with insulin-dependent diabetes mellitus.
AB  - We determined the percentage of circulating natural killer (NK) cells, using the
      monoclonal antibodies anti-CD57 and anti-CD16, NK cytotoxic activity (lytic
      units/10(6)) and lymphokine-activated killer (LAK) activity in 25 IDDM patients
      aged 3-23 years, 12 with disease for < 1 year (Group I) and 13 with disease for >
      3 years (Group II). Nine age-matched healthy subjects served as controls. The
      percentage of CD57+ cells was similar in IDDM patients and controls, while the
      percentage of CD16+ cells was lower in IDDM patients (P < 0.05) than in controls.
      NK cell cytotoxic activity was lower in IDDM patients than in controls (P <
      0.01), in Group I and II compared with controls (P < 0.005). LAK activity was
      similar in IDDM patients and in controls. No correlation was found between NK
      cytotoxic activity and metabolic control, HLA typing, while a negative
      correlation was found between NK cytotoxic activity and insulin requirement (P <
      0.05). The decreased NK cytotoxic activity observed in our patients, in
      particular in long-standing diabetics, with normal NK cell number, could be due
      to a qualitative defect of the NK cells, or to a deficient IL-2 and/or TNF-alpha
      production, or to a immunomodulatory or immunosuppressing effect of insulin.

PMID- 7516852
TI  - Metabolism of 3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2 (1H)-one (L
      696,229), an HIV-1 reverse transcriptase inhibitor, by rat liver slices and in
      humans.
AB  - Healthy subjects were administered single oral doses of 800 mg or 400 mg 3-[2
      (benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-o ne (L-696,229), a
      nonnucleoside inhibitor of the human immunodeficiency virus-type 1 (HIV-1)
      reverse transcriptase (RT). Plasma or urine samples were collected over a period
      of 48 hr. Pooled plasma (0.5-6 hr) and urine (0-24 hr) samples were analyzed by
      HPLC-UV and HIV-1 RT inhibition assay using poly rC.dG as a template primer. The
      parent compound and several common metabolites were detected in both samples. The
      metabolic profiles were also similar to those obtained from a rat liver slice
      incubation with [3H]L-696,229. The in vitro metabolites were identified by NMR
      and MS as 5 alpha-hydroxyethyl- (major), 5,6-dihydrodiol-, 6'-hydroxy-, 6
      hydroxymethyl-, and 5-vinyl analogs, and a benzoxazole ring hydrolysis product.
      Most of the significant metabolites in human plasma and urine were found to be
      identical to the in vitro metabolites, as established by HPLC-UV and MS.
      Hydrolysis of the plasma and urine with beta-glucuronidase/sulfatase indicated
      the presence of significant amounts of conjugates of the parent compound and 5
      alpha-hydroxyethyl metabolite. Most of the other primary metabolites were also
      present in conjugated forms, albeit in small quantities. In addition, two
      secondary metabolites were isolated and identified from the hydrolyzed urine as 5
      acetyl-6'-hydroxy- and 5 alpha-hydroxyethyl-6-hydroxymethyl- analogs.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7516853
TI  - Metabolism of isbufylline in humans. Isolation, identification, and synthesis of
      plasma and urine metabolites.
AB  - Isbufylline metabolism after oral administration to humans was studied. The main
      metabolites detected by the HPLC method, in plasma, were 1-methyl-7-(2-hydroxy-2
      methyl-propyl) xanthine (I), 1,3-dimethyl-7-(2-hydroxy-2-methyl-propyl) xanthine
      (II), and 1-methyl-7-(2-methyl-propyl) xanthine (III). The main metabolites
      detected in urine were 1-methyl-7-(2-hydroxy-2-methyl-propyl) xanthine (I), 1,3
      dimethyl-7-(2-carboxy-propyl) xanthine (IV), and 1,3-dimethyl-7-(2-hydroxymethyl
      propyl) xanthine glucuronic acid (V)-Gluc. They were isolated by HPLC, identified
      by GC/MS, HPLC/MS, or HPLC/MS/MS, and finally synthesized. Recovery of these
      metabolites, along with the absence of unmetabolized isbufylline in the urine,
      indicated biotransformation and renal excretion as the main routes of isbufylline
      elimination in humans. HPLC quantitation of the characterized urine metabolites
      revealed that 49% of the drug was eliminated as (I), 9% as (V)-Gluc, and 5% as
      (IV).

PMID- 7516854
TI  - In vitro metabolism of L-696,229, an HIV-1 reverse transcriptase inhibitor in
      rats and humans. Hepatic and extrahepatic metabolism and identification of
      enzymes involved in the hepatic metabolism.
AB  - The metabolism of L-696,229, 3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin
      2(1H)-o ne, a potent human immunodeficiency virus-type 1 reverse transcriptase
      inhibitor, by rat liver, lung, gut, and kidney microsomes has been studied. L
      696,229 was metabolized by rat liver microsomes to several products: the 5 alpha
      hydroxyethyl (M1); 5,6-dihydrodiol (M2); 6'-hydroxy (M3); 6-hydroxymethyl (M4);
      and 5-vinyl (M5) metabolites. For these pathways, liver was the most active
      metabolizing organ, whereas lung was the major extrahepatic organ in the drug
      metabolism. In all tissues tested, M1 was the major metabolite. With the
      exception of M3, gender differences in the hepatic formation of all metabolites
      were observed. Enzymes responsible for the hepatic metabolism of L-696,229 in
      rats were also investigated using various enzyme inducers and polyclonal
      antibodies to rat P-450. Treatment of male rats with dexamethasone (DX) or
      phenobarbital (PB) caused significant increases in the hepatic formation of the
      gender-dependent metabolites. Methylcholanthrene (3-MC) greatly enhanced the
      hepatic formation of M1, M3, and M4. Immunoinhibition studies suggested that
      CYP2B1/2 and 2E1 were not involved in L-696,229 metabolism, whereas CYP1A was
      partly responsible for the formation of M1 in untreated rats. CYP3A played an
      important role in the formation of M1, M2, M4, and M5 in untreated and DX-treated
      rats. In PB-treated rats, CYP2B1/2 was involved in the increased formation of M1
      and M4, whereas CYP3A was partly involved in the enhanced M2 and M4 formation,
      and primarily responsible for the increased M5 formation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7516855
TI  - The influence of protease inhibitors of the organism, especially bovine
      aprotinin, on the production of virulent hog cholera virus in tissue cultures.
AB  - The influence of biological protease inhibitors, especially aprotinin, on the
      production of virulent hog cholera virus in cell cultures. Production of number
      and size of fluorescent plaques after infection PK 15 cells with HC virus
      depended on properties of fetal calf sera added to the medium. By affinity
      chromatography on bovine alpha-chymotrypsin bound to CM-cellulose inhibitory
      proteins against chymotrypsin-like proteases could be eliminated from inhibiting
      sera. The fraction free from inhibitors did not inhibit plaque formation of HC
      virus in contrast to the fraction containing the eluted inhibitor(s). The
      inhibitory properties of fetal calf sera could be measured by a plaque inhibition
      test. By this test no inhibitory component could be demonstrated in 30 individual
      serum samples from pigs which on subsequent infection with HC virus exhibited
      virus growth to high titres. The serum from one pig, however, was found to
      inhibit HC virus plaque formation in PK 15 cells. When infected, this animal
      reacted with an unexpected low virus replication and mild disease symptoms. The
      production of virulent HC virus could likewise be inhibited by addition to the
      medium of the bovine protease inhibitor aprotinin; the degree of inhibition being
      dependent on the concentration. Virulent virus was produced again after
      elimination of this inhibitor from the medium. A weak inhibitory effect on plaque
      formation was also achieved by addition of the protease inhibitor chymostatin (3
      mg/5 mg) and human alpha 1x plasma inhibitor to the medium of infected cells. The
      inhibitory effect appears to be very specific.

PMID- 7516856
TI  - Selecting appropriate antihypertensive drug dosages.

PMID- 7516857
TI  - Gangliosides. Their role in clinical neurology.
AB  - Gangliosides are normal constituent of mammalian vertebrate cell membranes and
      are particularly abundant in the central and peripheral nervous systems. The
      biological effects of exogenously administered gangliosides have been extensively
      investigated in vitro and in experimental animal models where they have
      neuronotrophic and neuritogenic properties. Despite these findings there is still
      little evidence that treatment with parenteral gangliosides in humans can be
      effective in peripheral neuropathies or other neuromuscular diseases. The initial
      preliminary reports on the positive effects of GM1 in cerebrovascular diseases
      and spinal cord injury need to be confirmed in larger controlled trials. At the
      same time the occasional development of an acute motor neuropathy clinically
      presenting as the Guillain-Barre syndrome and associated with high titres of anti
      ganglioside antibodies highlights the risks of their widespread use before more
      consistent data on their efficacy become available.

PMID- 7516858
TI  - The clinical potential of renin inhibitors and angiotensin antagonists.
AB  - The renin angiotensin system is a major contributor to the pathophysiology of
      cardiovascular diseases such as congestive heart failure and hypertension. For
      this reason, attempts to specifically block this system have been a
      pharmacological goal for over 25 years. Blockade of the renin system has been
      attempted at 3 pivotal sites: the rate limiting angiotensinogen-renin step,
      conversion of angiotensin I to angiotensin II, and the active receptor sites for
      the terminal products of angiotensin II and aldosterone. Converting enzyme
      inhibitors have been successfully studied and utilised in clinical cardiovascular
      disorders, but questions persist regarding the specificity of their action. Thus,
      other more specific approaches remain under evaluation. Inhibition of the action
      of renin on angiotensinogen was demonstrated with early inhibitory peptides and
      in experimental studies with specific antibodies. Most currently available renin
      inhibitors are nonpeptides, which nonetheless require intravenous administration.
      An oral renin inhibitor with clinical effects has been evaluated in early human
      trials. Like renin inhibitors and converting enzyme inhibitors, specific
      angiotensin antagonists were studied early in the course of renin system
      pharmacological blockade. Early angiotensin antagonists were limited, due to the
      requirement for intravenous administration and because of their short half-lives.
      They also had the potential for mixed agonist/antagonist physiological and
      pharmacological effects, which could result in a pressor, rather than a
      depressor, response. The angiotensin receptor antagonists have the appeal of
      blocking the specific receptor at its target tissue site, analogous to other well
      described systems. Newer angiotensin antagonists do not have the limitations of
      the precursor peptides. Losartan (DUP753) is a specific angiotensin II AT1
      receptor antagonist. It is orally effective without agonist activity, and has
      high receptor binding characteristics. Early studies indicate that it is a
      specific probe of the renin system, and is providing newer insights into the role
      of the renin system in cardiovascular disorders. Emerging clinical studies
      indicate that it is effective for blood pressure reduction and as a vasodilator.
      Aldosterone antagonists such as spironolactone have been available for decades.
      Spironolactone is being used in an ongoing trial to assess the impact of combined
      converting enzyme and aldosterone inhibition. Newer aldosterone antagonists could
      add to targeted blockade of aldosterone without the adverse effects of the
      precursor compound, and the potential for combined specific renin system
      blockade.

PMID- 7516860
TI  - Glycaemia control in diabetes mellitus. Towards the normal profile?
AB  - The Diabetes Control and Complications Trial and the Stockholm Study have
      conclusively demonstrated that improving the blood glucose control in patients
      with insulin-dependent diabetes mellitus (IDDM) reduces the risk of developing
      retinopathy, nephropathy and neuropathy. Each patient with IDDM should be
      carefully evaluated for the appropriateness of institution of an intensive
      insulin treatment programme. In particular, the risk of severe hypoglycaemia must
      be considered and the goals modified if necessary to reduce the risk. Successful
      implementation of an intensive treatment programme requires an experienced
      healthcare team and a knowledgeable and well motivated cooperative patient.
      Several variations of intensive treatment programmes can be used, with no
      definite superiority of one treatment method over the others. Individualization
      is the key to success. Each programme has the same general principles. Regular
      insulin is used to control the postprandial glucose excursion and a slow infusion
      of regular insulin by a pump or injected intermediate or long-acting insulin is
      used to balance fasting glucose utilisation and production. The treatment will
      not be successful without self-monitoring of blood glucose by the patient and
      frequent adjustment of the insulin doses to compensate for variations in blood
      glucose levels, diet and activity. The treatment should be followed with
      quarterly glycated haemoglobin determinations and a regular follow-up plan.
      During follow-up the main challenge for the healthcare team will be to maintain
      motivation in the patient and to assist with behaviour modification. A detailed
      understanding of intensive treatment programmes may be beyond the skill of the
      average primary care physician, but any physician caring for patients with
      diabetes will benefit from an understanding of the general treatment principles
      outlined in this article.

PMID- 7516859
TI  - Use of psychotropic drugs in patients with HIV infection.
AB  - Psychotropic drugs are frequently employed to treat the wide range of
      neuropsychiatric syndromes that patients infected with the human immunodeficiency
      virus (HIV) may develop. In order to administer these agents properly, physicians
      should take certain factors into account: the central nervous systems of these
      patients are often impaired, the patients tend to suffer from medical illnesses,
      and they may be taking various other drugs. The possible interactions between
      substances taken by these patients may sometimes make it necessary to adjust the
      dosage of psychotropic agents administered. In addition, some of the
      antimicrobial, antifungal and antiviral agents used in the management of HIV
      infection may have adverse effects that include neuropsychiatric symptoms. The
      use of antipsychotic agents in these patients frequently results in the
      development of extrapyramidal symptoms. Tricyclic antidepressants are not well
      tolerated by patients with AIDS, due to the anticholinergic effects of these
      agents. The new antidepressants, which have fewer and milder adverse effects, are
      safer and have shown their efficacy in the treatment of the depressive episodes
      often seen in HIV-infected patients. Benzodiazepines must be prescribed with
      caution in patients with HIV infection and organic brain syndrome, since they can
      produce amnesia, confusion, lack of inhibition and paradoxical reactions. The
      indications for the use of psychostimulants in certain clinical situations, such
      as HIV-associated dementia and depression, is open to debate. Opiates are
      indicated in pain treatment, and in methadone maintenance programmes. Lithium and
      carbamazepine are advisable only in very restricted situations.

PMID- 7516865
TI  - Recombinant thyroid peroxidase-specific autoantibodies. II. Role of individual
      heavy and light chains in determining epitope recognition.
AB  - Most thyroid peroxidase (TPO) autoantibodies in man recognize closely associated
      epitopes in two domains (A and B) on TPO. These epitopes were defined by
      recombinant monoclonal human autoantibodies expressed as antigen-binding
      fragments [F(ab)]. Only five heavy (H) and light (L) chain gene combinations
      encoded 34 F(ab), all of which have high affinity (Kd, approximately 10(-10) M)
      for TPO. We, therefore, investigated the roles of H and L chain genes in TPO
      domain recognition in two ways. First, we created hybrid F(ab) by forced
      recombination of H and L chain genes from 4 F(ab) recognizing the A or B domains.
      These hybrid F(ab) proteins, expressed in bacteria, bound extremely poorly (or
      not at all) to TPO, even at concentrations more than 100-fold higher than those
      required for detection of TPO binding by the original F(ab). Nucleotide
      sequencing of the cDNA as well as gel electrophoresis of the expressed proteins
      confirmed that poor hybrid F(ab) binding to TPO was not the result of cloning
      artifacts. Therefore, contrary to prevailing views on combinatorial libraries, we
      found no tolerance for H and L chain cross-combinations in high affinity TPO
      binding. These observations strengthen the likelihood that the H and L chain
      combinations from combinatorial libraries reflect those of TPO autoantibodies in
      vivo. In a second approach to examine the roles of H and L chains in TPO binding,
      we focused on three original F(ab) with similar L chains (encoded by KL012-like
      germline genes) and similar H chains (encoded by V1-3B-like germline genes), but
      different diversity (D) regions. All F(ab) bound predominantly to TPO domain A,
      as observed previously for a F(ab) with a KL012 L chain and a different H chain.
      Conversely, a F(ab) with a V1-3B-like H chain but a different L chain (A') bound
      to TPO domain B. These data indicate that the L chain plays a major role in
      defining TPO epitope recognition.

PMID- 7516864
TI  - Insulin and insulin-like growth factor-I receptors similarly stimulate
      deoxyribonucleic acid synthesis despite differences in cellular protein tyrosine
      phosphorylation.
AB  - Signal transduction pathways stimulated by insulin or insulin-like growth factor
      I (IGF-I) were compared in transfected NIH3T3 fibroblast cell lines expressing
      the human insulin receptor, IGF-I receptor, or a chimeric IGF-I receptor with its
      carboxy-terminal tail replaced with that of the insulin receptor (approximately 1
      x 10(6) receptors/cell). Although receptor autophosphorylation was very similar
      in the three cell lines overexpressing receptors (EC50 = 1-3 nM), there were
      differences detected in the protein tyrosine phosphorylation stimulated by
      insulin and IGF-I in these cells. Although no substrates specific for the insulin
      receptor were detected, phosphorylation of a 170-kilodalton (kDa; IRS-1) and a 70
      kDa protein was 10 times more sensitive to insulin than to IGF-I (EC50 = 1.5-2.5
      vs. 14-23 nM). The chimeric receptor stimulated significantly lower levels of
      phosphorylation of several proteins relative to the wild-type IGF-I receptor.
      Activation of phosphatidylinositol 3'-kinase paralleled phosphorylation of the
      170- and 70-kDa proteins. Despite these differences in protein tyrosine
      phosphorylation, stimulation of mitogen-activated protein (MAP) kinase and DNA
      synthesis were very similar in the three cell lines overexpressing receptors.
      Little difference was detected in Shc phosphorylation or MAP kinase activation
      through the three receptors, although activation of MAP kinase was more
      efficiently coupled to the platelet-derived growth factor receptor than to any of
      the overexpressed receptors. All three receptors stimulated DNA synthesis to
      levels comparable to 10% serum, with similar sensitivities (EC50 = 1.5-3.5 nM).

PMID- 7516866
TI  - Cloning, expression, and mutational analysis of the pigeon prolactin receptor.
AB  - A full-length PRL receptor (PRLR) complementary DNA from pigeons was obtained by
      screening pigeon crop sac libraries and by reverse transcription coupled with
      polymerase chain reaction. The deduced sequence of 830 amino acids revealed a new
      member of the PRL/GH/cytokine receptor superfamily; it contained a single
      transmembrane domain, all of the conserved cysteine pairs and the WSxWS motif in
      its extracellular domain, and a conserved proline-rich motif in its intracellular
      domain. The cytoplasmic domain of the pigeon PRLR was similar to the long form of
      mammalian PRLRs in both length and general sequence characteristics. There was no
      evidence of short or intermediate form receptor in any of the clones examined.
      Unlike mammalian PRLRs, which have a single extracellular domain, the pigeon PRLR
      had two highly homologous units in its extracellular domain. Amino acid sequences
      of the repeated units were 64% identical to each other and were 52-59% (membrane
      distal unit) and 60-71% (membrane-proximal unit) identical to the extracellular
      domain of the mammalian PRLRs. To study the significance of the repeated
      extracellular units in pigeons, a mutated pigeon PRLR complementary DNA that
      contained only the membrane-proximal unit in the extracellular domain was
      constructed. Both the wild-type and mutated pigeon PRLRs bound to rat PRL (rPRL)
      with equally high affinities (Ka = 0.6 nM-1). The ligand specificities of both
      forms of the pigeon PRLR were also identical.

PMID- 7516862
TI  - Parnaparin. A review of its pharmacology, and clinical application in the
      prevention and treatment of thromboembolic and other vascular disorders.
AB  - Parnaparin is a low molecular weight (LMW) heparin which, like other members of
      its class, apparently demonstrates a greater antithrombotic effect relative to
      its anticoagulant activity when compared with the unfractionated heparin
      (heparin) from which it is derived. Moreover, subcutaneous parnaparin has a
      greater bioavailability and longer half-life than heparin, permitting once-daily
      administration for the prophylaxis of deep venous thrombosis (DVT) or the
      treatment of established vascular disorders. Prophylaxis with a 7-day regimen of
      parnaparin 3200 or 6400 IUaXa/day has consistently been associated with a lower
      incidence of confirmed DVT compared with usual prophylactic regimens of heparin.
      This intertreatment difference reached statistical significance in a large
      multicentre study involving a total of 610 surgical patients (3.2% for parnaparin
      vs 6.3% for heparin). Thus far, however, comparisons of parnaparin with other LMW
      heparins for this indication are unavailable. Parnaparin has demonstrated
      equivalent efficacy to heparin in the treatment of established vascular
      disorders, including phlebopathies and related syndromes, as well as peripheral
      arterial occlusive disease. Parnaparin also showed some benefit as an adjunctive
      therapy in patients with angina pectoris. The risk of general bleeding appears to
      be similar with parnaparin or heparin, although parnaparin results in fewer
      haematomas at the site of injection, partly because of the less frequent
      administration regimen. Parnaparin has also been associated with a lower
      incidence of pain and/or burning sensation at the injection site compared with
      heparin. As with other LMW heparins, the possibility that parnaparin will be
      infrequently associated with thrombocytopenia cannot be excluded. Thus,
      parnaparin may be preferred over traditional heparin for the prophylaxis of
      thromboembolic events in surgical patients (particularly those at high risk for
      DVT), as well as the treatment of established vascular disorders with a
      thrombotic aetiology. Compared with heparin, parnaparin offers the advantages of
      a more convenient administration regimen coupled with improved local
      tolerability. However, the therapeutic advantages of parnaparin relative to other
      LMW heparins have yet to be established in large scale comparative trials.

PMID- 7516861
TI  - Sumatriptan. A reappraisal of its pharmacology and therapeutic efficacy in the
      acute treatment of migraine and cluster headache.
AB  - Sumatriptan is a potent and selective agonist at a vascular serotonin1 (5
      hydroxytryptamine1; 5-HT1) receptor subtype (similar to 5-HT1D) and is used in
      acute treatment of migraine and cluster headache. Following administration of
      sumatriptan 100mg orally, relief of migraine headache (at 2 hours) was achieved
      in 50 to 67% of patients compared with 10 to 31% with placebo in controlled
      clinical trials. In a comparative study, oral administration of sumatriptan 100mg
      consistently achieved significantly greater response rates than a fixed
      combination of ergotamine 2mg plus caffeine 200mg during 3 consecutive migraine
      attacks (66 vs 48% for first attack). Oral sumatriptan 100mg was also more
      effective than aspirin 900mg plus metoclopramide 10mg orally in a similar study.
      In the majority of controlled clinical trials, headache relief (at 1 hour after
      administration) was achieved in 70 to 80% of patients with migraine receiving
      sumatriptan 6mg subcutaneously compared with 18 to 26% of placebo recipients.
      Approximately 40% of patients who initially responded to oral or subcutaneous
      sumatriptan experienced recurrence of their headache, usually within 24 hours,
      but the majority of these patients responded well to a further dose of
      sumatriptan. Patients with cluster headache were treated for acute attacks with
      sumatriptan 6mg subcutaneously or placebo in 2 crossover trials. Headache relief
      was achieved within 15 minutes in 74 and 75% of patients receiving sumatriptan in
      these studies compared with 26 and 35%, respectively, with placebo. Patients
      receiving sumatriptan 12mg had a similar response rate as those receiving 6mg,
      but the higher dose was associated with an increased incidence of adverse events.
      Based on extensive safety data pooled from controlled clinical trials,
      sumatriptan is generally well tolerated and most adverse events are transient.
      The most frequently reported adverse events following oral administration include
      nausea, vomiting, malaise, fatigue and dizziness. Injection site reactions (minor
      pain and redness of brief duration) occur in approximately 40% of patients
      receiving subcutaneous sumatriptan, although the incidence appears to be markedly
      reduced when patients self-administer the drug with an auto-injector. Chest
      symptoms (mainly tightness and pressure) occur in 3 to 5% of sumatriptan
      recipients, but have not been associated with myocardial ischaemia except in a
      few isolated cases. Sumatriptan is contraindicated in patients with ischaemic
      heart disease, angina pectoris including Prinzmetal (variant) angina, previous
      myocardial infarction and uncontrolled hypertension, but is not contraindicated
      in patients with migraine and asthma. Data from long term studies in acute
      treatment of migraine and cluster headache suggest that sumatriptan remains
      effective and well tolerated over several months.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7516867
TI  - Human osteoblast-like cells produce nitric oxide and express inducible nitric
      oxide synthase.
AB  - Nitric oxide (NO) is a short-lived free radical that plays an important
      regulatory role in several biological processes. Cytokines such as interleukin-1,
      tumor necrosis factor, and interferon-gamma have been shown to stimulate NO
      production in many cells types. Although these cytokines are known to have potent
      effects on bone remodeling and osteoblast function, the role of NO as an effector
      molecule in bone has been little studied. Here we investigate the effects of
      cytokines and calciotropic hormones on NO production by human osteoblast-like
      cells (hOB) and the role of NO as a modulator of osteoblast growth. Unstimulated
      hOB produced little NO, as reflected by measurement of nitrite concentrations in
      hOB-conditioned medium. NO production was not significantly altered by PTH and
      1,25-dihydroxyvitamin D or human recombinant interleukin-1 beta (10 U/ml), tumor
      necrosis factor-alpha (25 ng/ml), and interferon-gamma (100 U/ml) individually.
      Combinations of all three cytokines at these concentrations, however,
      dramatically increased both NO generation and cGMP production. The stimulatory
      effect of cytokines on NO production began 12 h after exposure and was inhibited
      by cycloheximide, actinomycin-D, dexamethasone, and the competitive inhibitor of
      NO synthase L-NG-monomethylarginine. Reverse transcription/polymerase chain
      reaction analysis of hOB RNA, followed by direct sequencing of the amplified
      products, showed that hOB express the inducible, rather than the endothelial or
      neuronal, forms of NO synthase. Cytokine-induced increases in NO production were
      associated with a marked inhibition of [3H]thymidine uptake to less than 10% of
      that observed in control cultures. Abrogation of NO synthesis with L-NG
      monomethylarginine under these conditions significantly increased [3H]thymidine
      uptake to approximately 20% of the control value, suggesting that NO may partly
      be responsible for the inhibition of osteoblast proliferation induced by these
      cytokines. Our data indicate that proinflammatory cytokines induce NO production
      in osteoblast-like cells and show and that this mediator plays a role in
      regulating cell growth. These findings may have important implications for the
      pathogenesis and management of bone loss in diseases associated with cytokine
      activation, such as rheumatoid arthritis.

PMID- 7516869
TI  - Insulin-like growth factor-binding protein-3 (IGFBP-3) concentration in rat
      Sertoli cell-conditioned medium is regulated by a pathway involving association
      of IGFBP-3 with cell surface proteoglycans.
AB  - Rat Sertoli cells in culture produce insulin-like growth factor-I (IGF-I), and
      IGF-binding protein-3 (IGFBP-3) is the predominant IGFBP. Previous studies
      suggested that the concentration of IGFBP-3 in Sertoli cell-conditioned medium is
      regulated by a clearance pathway involving association of IGFBP-3 with the
      Sertoli cell surface. The purpose of these studies was to characterize further
      the nature of the interaction of IGFBP-3 with the cell surface and to examine how
      this interaction might be regulating IGFBP-3 concentrations in conditioned
      medium. Recombinant nonglycosylated human IGFBP-3 was added to cultured Sertoli
      cells derived from 15-day-old rats, and the change in concentration over time in
      the medium was measured by [125I]IGF-I ligand blot analysis and Western blot
      analysis using an antiserum specific for human IGFBP-3. Chloroquine, an inhibitor
      of lysosomal enzymes involved in internalization of proteins and reduction of
      temperature, inhibited IGFBP-3 reduction in Sertoli cell medium. Soluble heparin,
      at a half-maximal concentration of approximately 5 microgram/ml, inhibited the
      decrease in IGFBP-3 in the medium. In addition, soluble heparin decreased the
      amount of IGFBP-3 detectable on the cell surface, as determined by performing
      ligand blots on plasma membrane preparations. Finally, pretreatment of Sertoli
      cells with sodium chlorate, an inhibitor of cell surface proteoglycan sulfation,
      also retarded the decrease in recombinant IGFBP-3. Taken together, these data
      suggest that an important mechanism influencing the concentration of IGFBP-3 3 in
      Sertoli cell-conditioned medium is a pathway involving IGFBP-3 interaction with
      the cell surface proteoglycans.

PMID- 7516863
TI  - Levofloxacin. A review of its antibacterial activity, pharmacokinetics and
      therapeutic efficacy.
AB  - Levofloxacin, an oral fluoroquinolone antibacterial agent, is the optical S-(-)
      isomer of ofloxacin. In vitro it is generally twice as potent as ofloxacin.
      Levofloxacin is active against most aerobic Gram-positive and Gram-negative
      organisms and demonstrates moderate activity against anaerobes. Drug penetration
      into body tissues and fluids is rapid and widespread after oral administration.
      In clinical trials conducted in Japan, oral levofloxacin has demonstrated
      antibacterial efficacy against a variety of infections, including upper and lower
      respiratory tract, genitourinary, obstetric, gynaecological and skin and soft
      tissues. In comparative trials with ofloxacin, levofloxacin, at half the daily
      dosage of ofloxacin, showed equivalent efficacy and a reduced incidence of
      adverse effects in the treatment of lower respiratory tract and complicated
      urinary tract infections. Levofloxacin has a tolerability profile similar to that
      of other oral fluoroquinolones, with gastrointestinal and central nervous system
      effects reported most commonly. Theophylline dosage adjustment does not appear to
      be necessary in patients receiving concomitant levofloxacin. Coadministration
      with antacids or with other drugs containing divalent or trivalent cations
      reduces levofloxacin absorption. Thus, levofloxacin has potential as a broad
      spectrum antibacterial drug in the treatment of a variety of infections. However,
      clinical trials recruiting non-Japanese patients are in progress and these
      results will form a basis on which future recommendations for the broader use of
      levofloxacin can be made.

PMID- 7516868
TI  - Cytokine regulation of parathyroid hormone-related protein messenger ribonucleic
      acid levels in mouse spleen: paradoxical effects of interferon-gamma and
      interleukin-4.
AB  - Under normal physiological conditions, PTH-related protein (PTHrP) is produced in
      a wide variety of tissues and is thought to act locally in an autocrine or
      paracrine fashion more analogous to cytokines than to classic hormones such as
      PTH. In addition, we have recently shown that, like cytokines, PTHrP is induced
      in the spleen during the response to sublethal doses of endotoxin
      [lipopolysaccharide (LPS)] an effect that is mediated by tumor necrosis factor
      (TNF). As complex cytokine cascades are induced in response to infectious or
      inflammatory stimuli, the effects of other prototypical inflammatory [interferon
      gamma (IFN gamma)] or antiinflammatory [interleukin-4 (IL-4)] cytokines on PTHrP
      gene expression were studied. Paradoxically, IFN gamma (50 micrograms), a
      cytokine that usually synergizes with TNF, inhibited LPS induction of splenic
      PTHrP messenger RNA (mRNA) levels in LPS-sensitive C3H/OuJ (OuJ) and LPS
      resistant C3H/HeJ (HeJ) mice. The stimulation of splenic PTHrP mRNA levels caused
      by the administration of TNF alpha or interleukin-1 beta was similarly inhibited
      by IFN gamma, a type II interferon. In contrast, IFN alpha (50 micrograms), a
      type I interferon, stimulated splenic levels of PTHrP mRNA. IL-4, a prototypical
      antiinflammatory cytokine, also had a paradoxical effect on LPS induction of
      splenic PTHrP mRNA levels. Instead of inhibiting LPS induction of splenic PTHrP
      mRNA levels in OuJ or HeJ mice, IL-4 (200 ng) actually stimulated PTHrP mRNA
      levels. These complex cytokine interactions suggest that the expression of PTHrP
      in response to infectious or inflammatory stimuli depends on the counterbalancing
      effects of the specific cytokine networks induced by each stimulus.

PMID- 7516871
TI  - Identification of thyroid hormone receptor isoforms in thyrotropin-releasing
      hormone neurons of the hypothalamic paraventricular nucleus.
AB  - TRH gene expression in hypophysiotropic neurons of the hypothalamic
      paraventricular nucleus (PVN) is under regulation by thyroid hormone circulating
      in the bloodstream. To determine whether thyroid hormone could exert effects
      directly on TRH-producing neurons in the PVN, the presence of thyroid hormone
      receptors (TR) in these neurons was determined by double labeling
      immunocytochemical techniques, using specific antiserum to each of the functional
      TRs, TR alpha 1, TR beta 1, and TR beta 2, followed by antiserum to prepro-TRH
      (25-50) as a marker for TRH neurons. In addition, the presence of the TR variant,
      TR alpha 2, was sought in these cells. Immunoreactive TR alpha 1 and TR beta 2
      were found in the greatest percentage of TRH neurons in the PVN (91.1 +/- 2.5%
      and 83.8 +/- 2.1%) and intensely stained the nucleus. Immunoreactive TR beta 1
      was also found in the majority of TRH neurons, but stained PVN cells only lightly
      compared to the other TRs. TR alpha 2 was found to coexist in only a minority of
      TRH neurons in the PVN and also lightly immunostained the nucleus compared to its
      more intense labeling in other regions of the brain. We conclude that
      hypophysiotropic TRH neurons contain functional TRs, and therefore, these neurons
      could be directly influenced by thyroid hormone. The relative paucity of TR alpha
      2 in these cells could contribute to the selectivity of this population of TRH
      neurons to the effects of circulating levels of thyroid hormone.

PMID- 7516870
TI  - Insulin-like growth factor-II (IGF-II), type 2 IGF receptor, and IGF-binding
      protein-2 gene expression in rat lung alveolar epithelial cells: relation to
      proliferation.
AB  - Pulmonary alveolar type 2 cells act as a reservoir of stem cells which can be
      induced to proliferate during periods of lung growth and repair after lung
      injury. Despite the importance of this process, the mechanisms that regulate type
      2 cell proliferation have not been well characterized. We show in this study that
      insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) accumulates to high
      levels in culture medium of growth-arrested type 2 cells. This is associated with
      an increased expression of IGFBP-2 messenger RNA (mRNA). Study of the other
      components of the IGF system also reveals induction of IGF-II and type 2 IGF
      receptor mRNA during the process of type 2 cell block of proliferation. When
      growth-arrested cells are allowed to resume proliferation by the addition of
      serum, the level of expression of IGFBP-2, type 2 IGF receptor, and IGF-II
      rapidly decreased. Despite the similarities in the timing of induction, it is
      likely that these components are not necessarily linked to mediate effects
      through a single pathway. Indeed, we show that the addition of conditioned medium
      from growth-arrested cells on proliferative cells results in down-regulation of
      IGFBP-2 and increased expression of IGF-II and type 2 IGF receptor mRNA.
      Treatment of the cells with various concentrations of IGF-II affects only the
      level of expression of type 2 IGF receptor, whereas IGF-I and insulin appear to
      influence only the expression of IGFBP-2. From the results presented in this
      study, it can be suggested that IGFBP-2, IGF-II, and type 2 IGF receptor play an
      important role in the transition of lung alveolar epithelial cells in and out of
      the cell cycle.

PMID- 7516872
TI  - Cell proliferation and renal carcinogenesis.
AB  - Enhanced cell proliferation occurs at several stages of renal tumorigenesis.
      Initiation by genotoxic nephrocarcinogens such as dimethylnitrosamine (DMN) is
      likely a result of DNA damage coupled with an initial burst of DNA synthesis
      associated with the cytotoxic effects of the compound. The level of initiation by
      DMN can be further enhanced by unilateral nephrectomy or hydronephrosis, which
      induces a brief burst of cell proliferation followed by tumorigenesis in the
      contralateral kidney. The role of sustained cell proliferation in renal tumor
      development is less well understood. The most compelling evidence comes from
      studies with nongenotoxic renal carcinogens such as unleaded gasoline and d
      limonene, which induce alpha 2u-globulin (alpha G) nephropathy and renal
      epithelial tumors exclusively in male rats. Sustained increases in cell
      proliferation in these studies depend on the presence of a chemical-alpha G
      complex in phagolysosomes of P2 proximal tubule cells, which results in
      cytotoxicity and compensatory hyperplasia only in male F344 rats, but not female
      F344 rats or alpha G deficient male NBR rats. Furthermore, initiation-promotion
      experiments demonstrated a strong correlation between the dose-response of cell
      proliferation and the incidence of preneoplastic and neoplastic lesions. Clearly,
      similar correlative studies with a number of other renal carcinogens and non
      carcinogens are warranted before general conclusions can be made. Cell
      proliferation is excessively elevated in tubules affected by chronic progressive
      nephropathy, but the significance of the lesion to renal carcinogenesis is
      unclear. Elucidating mechanisms of renal cell proliferation are necessary for our
      understanding of cause and effect relationships. An exciting recent finding is
      altered expression of transforming growth factor-alpha in hereditary rat renal
      cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516874
TI  - Retrospective study of possible alpha-2 mu-globulin nephropathy and associated
      cell proliferation in male Fischer 344 rats dosed with t-butyl alcohol.
AB  - Tert-butyl alcohol, an important commodity chemical, additive to unleaded
      gasoline, and contaminant of drinking water, was evaluated for toxicity and was
      found to enhance nephropathy in male Fischer 344 rats. Because male rats treated
      with t-butyl alcohol for 2 years had a low incidence of renal cortical tumors,
      additional renal sections for the 90-day toxicity study were examined for the
      presence of hyaline droplet accumulation, nephropathy, and evidence of
      replicative DNA synthesis (S-phase nuclei) to indirectly and retrospectively
      investigate a possible role of alpha-2 mu-globulin in the pathogenesis of the
      nephropathy. Dose levels for t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4%
      (w/v) administered in drinking water. Significant body weight gain depressions
      were observed in all treated males, and there was an absolute weight loss in the
      4% male group, none of which survived to the end of the study. Except for the 4%
      dose group, there was a treatment-related increase in hyaline droplet
      accumulation in the renal proximal tubules with crystalline, rectangular, and
      rhomboid forms of the protein evident. The severity of nephropathy was enhanced
      in treated rats, except for the 4% dose group. Replicative DNA synthesis, as
      measured by immunohistochemical staining for proliferating cell nuclear antigen,
      was increased in proximal tubules of rats dosed with 2% t-butyl alcohol. It is
      concluded that t-butyl alcohol exacerbated nephropathy in male Fischer 344 rats
      and increased renal accumulation of hyaline protein material consistent with
      alpha-2 mu-globulin deposition.

PMID- 7516875
TI  - Crystal structure and site-directed mutagenesis of a bleomycin resistance protein
      and their significance for drug sequestering.
AB  - The antibiotic bleomycin, a strong DNA cutting agent, is naturally produced by
      actinomycetes which have developed a resistance mechanism against such a lethal
      compound. The crystal structure, at 2.3 A resolution, of a bleomycin resistance
      protein of 14 kDa reveals a structure in two halves with the same alpha/beta fold
      despite no sequence similarity. The crystal packing shows compact dimers with a
      hydrophobic interface and involved in mutual chain exchange. Two independent
      solution studies (analytical centrifugation and light scattering) showed that
      this dimeric form is not a packing artefact but is indeed the functional one.
      Furthermore, light scattering also showed that one dimer binds two antibiotic
      molecules as expected. A crevice located at the dimer interface, as well as the
      results of a site-directed mutagenesis study, led to a model wherein two
      bleomycin molecules are completely sequestered by one dimer. This provides a
      novel insight into antibiotic resistance due to drug sequestering, and probably
      also into drug transport and excretion.

PMID- 7516873
TI  - Cellular origin of cancer: dedifferentiation or stem cell maturation arrest?
AB  - Given the fundamental principle that cancer must arise from a cell that has the
      potential to divide, two major nonexclusive hypotheses of the cellular origin of
      cancer are that malignancy arises a) from stem cells due to maturation arrest or
      b) from dedifferentiation of mature cells that retain the ability to proliferate.
      The role of stem cells in carcinogenesis is clearly demonstrated in
      teratocarcinomas. The malignant stem cells of teratocarcinomas are derived from
      normal multipotent stem cells and have the potential to differentiate into normal
      benign mature tissue. A widely studied model supporting dedifferentiation has
      been the putative origin of hepatocarcinomas from "premalignant" foci and nodules
      induced in the rat liver by chemicals. However, the dedifferentiation concept for
      hepatocarcinogenesis is challenged by more recent interpretations indicating that
      hepatocellular carcinoma arises from maturation arrest caused by aberrant
      differentiation of determined stem cells. Either hypothesis is supported by the
      cellular changes that occur in the rodent liver after different
      hepatocarcinogenic regimens. The formation of foci and nodules from altered
      hepatocytes supports dedifferentiation; the proliferation of small oval cells
      with the potential to differentiate into either biliary ducts or hepatocytes
      supports arrested maturation of determined stem cells. It is now postulated that
      foci and nodular change reflect adaptive changes to the toxic effects of
      carcinogens and not "preneoplastic" stages to cancer. The stem cell model
      predicts that genotoxic chemicals induce mutations in the determined stem cell
      which may be expressed in its progeny. Proliferation of initiated cells is
      induced by promoting events which also allow additional mutations to occur.

PMID- 7516876
TI  - Signal transduction pathways regulating Rho-mediated stress fibre formation:
      requirement for a tyrosine kinase.
AB  - Lysophosphatidic acid (LPA) and bombesin rapidly stimulate the formation of focal
      adhesions and actin stress fibres in serum-starved Swiss 3T3 fibroblasts, a
      process regulated by the small GTP binding protein Rho. To investigate further
      the signalling pathways leading to these responses, we have tested the roles of
      three intracellular signals known to be induced by LPA: activation of protein
      kinase C (PK-C), Ca2+ mobilization and decreased cAMP levels. Neither PK-C
      activation nor increased [Ca2+]i, alone or in combination, induced stress fibre
      formation, and in fact activators of PK-C inhibited this response to LPA and
      bombesin. The G(i)-mediated decrease in cAMP was not required for the response to
      LPA, and increased cAMP levels did not prevent stress fibre formation. In
      contrast, the tyrosine kinase inhibitor genistein inhibited the formation of
      stress fibres induced by both extracellular factors and microinjected Rho
      protein. Genistein also inhibited the Rho-dependent clustering of phosphotyrosine
      containing proteins at focal adhesions, and the increased tyrosine
      phosphorylation of several proteins including pp125FAK, induced by LPA and
      bombesin. This suggests a model where Rho-induced activation of a tyrosine kinase
      is required for the formation of stress fibres.

PMID- 7516879
TI  - Platelets and atherosclerosis.
AB  - Despite the broad array of mechanisms designed to protect the endothelial lining
      of every blood vessel in the body and maintain the fluid state of blood, injury
      does occur. Chronic and recurrent damage result in development of lesions
      characteristic of atherosclerosis. The loss of vascular integrity associated with
      the pathological process of atherogenesis triggers the haemostatic mechanism. As
      a result, fibrin and platelets become a part of atherosclerotic lesions and play
      a role in their progression. Growth of the plaques and destruction of normal
      endothelium triggers further involvement of platelets leading to occlusion of
      arteries in the heart and brain, resulting in myocardial infarction and stroke.
      Understanding the role of platelets in atherosclerosis and limiting its
      contribution may reduce morbidity and mortality of this dread disease.

PMID- 7516880
TI  - Markers of platelet activation in coronary heart disease patients.
AB  - We have applied flow cytometry to the detection of activated platelets in
      patients with coronary heart disease. Paraformaldehyde-fixed platelets were
      incubated with one of the following monoclonal antibodies (MAbs): Bx-1 (anti-GP
      Ib), AP-2 (anti-GP IIb-IIIa complex), VH10 (anti-GMP-140, a glycoprotein of the
      alpha-granule membrane), or PAC-1 (directed against an activation-dependent
      determinant on GP IIb-IIIa complexes). Bound antibody was quantitated after the
      addition of FITC-conjugated anti-immunoglobulin. This report highlights studies
      on 16 unstable angina patients undergoing transluminal angioplasty. Blood samples
      were taken at different periods before and after the angioplasty. Levels of
      activated platelets were variable, remaining in the 2-4% range of control donors
      for some, but increasing to 10-30% post-angioplasty for others (despite all
      patients receiving heparin and aspirin). Maximum numbers of activated platelets
      were detected at 24 or 48 h. Nonetheless, the amount of antibody bound to
      individual platelets rarely reached the levels seen when control platelets were
      stimulated with thrombin in vitro. Results with VH10 and PAC-1 often, but not
      always, correlated suggesting different pathways of platelet activation.

PMID- 7516877
TI  - The decoding region of 16S RNA; a cross-linking study of the ribosomal A, P and E
      sites using tRNA derivatized at position 32 in the anticodon loop.
AB  - A photo-reactive diazirine derivative was attached to the 2-thiocytidine residue
      at position 32 of tRNA(Arg)I from Escherichia coli. This modified tRNA was bound
      under suitable conditions to the A, P or E site of E.coli ribosomes. After photo
      activation of the diazirine label, the sites of cross-linking to 16S rRNA were
      identified by our standard procedures. Each of the three tRNA binding sites
      showed a characteristic pattern of cross-linking. From tRNA at the A site, a
      major cross-link was observed to position 1378 of the 16S RNA, and a minor one to
      position 936. From the P site, there were major cross-links to positions 693 and
      to 957 and/or 966, as well as a minor cross-link to position 1338. The E site
      bound tRNA showed major cross-links to position 693 (identical to that from the P
      site) and to positions 1376/1378 (similar, but not identical, to the cross-link
      observed from the A site). Immunological analysis of the concomitantly cross
      linked ribosomal proteins indicated that S7 was the major target of cross-linking
      from all three tRNA sites, with S11 as a minor product. The results are discussed
      in terms of the overall topography of the decoding region of the 30S ribosomal
      subunit.

PMID- 7516881
TI  - Antiplatelet drugs.
AB  - The evidence in support of the safety and efficacy of aspirin in the secondary
      prevention of platelet dependent vascular occlusion is compelling. The utility of
      this drug has stalled the development of potential competitors, such as
      thromboxane antagonists. The emergence of glycoprotein IIb/IIIa antagonists as
      the most promising competitors for aspirin has focused attention on the
      possibility of delivering these drugs at an effective dose safely.

PMID- 7516878
TI  - Adhesive proteins in platelet-endothelial interactions.
AB  - Adhesion molecules mediate the interaction between endothelium and platelets as
      well as other blood cells and the endothelium. The structure and function of some
      of these molecules will be reviewed and discussed. The expression of these
      molecules is largely affected by disease states such as hypertension, diabetes,
      and cardiac failure. Determination of adhesion molecules expressed on the surface
      of endothelial cells and platelets by cytoflowmetry enables a new approach to
      estimate the activity state of these cells and might be helpful to identify
      patients with an increased thrombotic risk.

PMID- 7516882
TI  - Role of neutrophils and mucosal blood flow in gastric adaptation to aspirin.
AB  - Gastric mucosa adapts to ulcerogenic action of aspirin but the mechanism of this
      phenomenon is unknown. In this study, acute gastric lesions were produced by
      single or repeated oral administration of acidified aspirin in rats with intact
      or deactivated (by capsaicin) sensory nerves and with intact or suppressed
      synthase of nitric oxide (NO). Single oral dose of aspirin produced a dose
      dependent increase in the area of gastric lesions accompanied by a significant
      increase in blood neutrophils, neutrophil infiltration into the mucosa,
      leukotriene B4 formation and almost complete suppression of prostaglandin
      synthesis. After repeated administration of aspirin, the mucosal damage
      progressively declined and this was accompanied by a significant augmentation in
      gastric blood flow. In addition, a reduction in blood neutrophil count, mucosal
      neutrophil infiltration and leukotriene B4 release was observed during this
      adaptation of the stomach to repeated aspirin insults. Capsaicin denervation of
      sensory nerves aggravated the damage induced by the first exposure of the stomach
      to aspirin and caused a significant reduction in gastric blood flow, but with
      repeated aspirin administration, gastric adaptation to this agent and a rise in
      gastric blood flow were observed. Pretreatment NG-nitro-L-arginine with (L-NNA),
      a specific inhibitor of nitric oxide synthase, eliminated the hyperemic response
      to repeated aspirin insults but failed to affect the adaptation to aspirin. We
      conclude that the rat stomach adapts readily to repeated aspirin insults despite
      sustained inhibition of prostaglandin biosynthesis and this adaptation appears to
      be mediated by a significant increase in gastric blood flow and a reduction in
      neutrophil activation and leukotriene B4 release.

PMID- 7516884
TI  - Comparative effects of N omega-nitro-L-arginine and N omega-nitro-L-arginine
      methyl ester on vasodilator responses to acetylcholine, bradykinin, and substance
      P.
AB  - N omega-Nitro-L-arginine methyl ester has been reported to have muscarinic
      receptor blocking activity whereas the nonesterified analog does not bind to
      muscarinic receptors. The present study was, therefore, undertaken to compare the
      inhibitory effects of N omega-nitro-L-arginine methyl ester with those of N omega
      nitro-L-arginine on baseline tone and on vasodilator responses to acetylcholine,
      bradykinin, and substance P in the mesenteric vascular bed of the cat under
      constant flow conditions. Administration of N omega-nitro-L-arginine methyl ester
      and N omega-nitro-L-arginine in doses of 100 mg/kg i.v. increased baseline tone
      in the mesenteric vascular bed and inhibited mesenteric vasodilator responses to
      acetylcholine, bradykinin, and substance P. The increase in mesenteric arterial
      perfusion pressure and the decrease in vasodilator responses to the three
      endothelium-dependent vasodilator agents following administration of N omega
      nitro-L-arginine methyl ester and N omega-nitro-L-arginine did not differ
      significantly. The nitric oxide synthase inhibitors did not attenuate vasodilator
      responses to agents that induce vasodilation by nonendothelium-dependent
      mechanisms and enhanced responses to the nitrovasodilators. Atropine blocked
      vasodilator responses to acetylcholine but did not alter responses to bradykinin
      or substance P. The similarity in the inhibitory effects of N omega-nitro-L
      arginine methyl ester and N omega-nitro-L-arginine on responses to acetylcholine,
      bradykinin, and substance P suggest that the L-arginine analog, N omega-nitro-L
      arginine, as well as the methyl ester of N omega-nitro-L-arginine, are useful
      probes for studying endothelium-dependent vasodilator responses in the mesenteric
      vascular bed of the cat.

PMID- 7516883
TI  - Manganese potentiation of nitric oxide-mediated vascular relaxation.
AB  - The half-life of nitric oxide (NO) and the relaxation of aortic-rings are
      enhanced by superoxide dismutase. Manganese and manganese-containing preparations
      have been reported to mimic superoxide dismutase activity. In the current study,
      manganese was tested for its ability to potentiate the activity of NO both in
      vitro and in vivo. Manganese relaxation of aortic segments was endothelium
      dependent as well as concentration dependent. Cyclic GMP concentrations in the
      segments were increased 2- and 4-fold with 5 and 300 microM manganese,
      respectively. N-Monomethyl-L-arginine pretreatment of aortic rings abolished the
      relaxation and cyclic GMP accumulation mediated by manganese. Infusion of
      manganese into conscious, restrained rats resulted in a decrease of blood
      pressure which was abolished by N-nitro-L-arginine pretreatment. Therefore,
      manganese may prolong the half-life of NO by a mechanism that mimics the action
      of superoxide dismutase resulting in potentiation of NO actions in vascular
      tissue.

PMID- 7516885
TI  - Comparison of tachykinin NK1 receptors in human IM9 and U373 MG cells, using
      antagonist (FK888, (+/-)-CP-96,345, and RP 67580) binding.
AB  - We have used one peptide (FK888) and two non-peptide ((+/-)-CP-96,345 and RP
      67580) antagonists, along with the preferred endogenous agonist, substance P, to
      compare the pharmacological (binding) profile of NK1 receptors expressed by human
      B lymphoblastoma (IM9) and astrocytoma (U373 MG) cells. Of the ligands tested,
      substance P was the most potent in both cell lines: binding affinities were 0.1
      nM for IM9 cells, and 0.3 nM for U373 MG cells, respectively. The high-affinity
      dipeptide antagonist, FK888, bound to NK1 receptors in both cell lines with
      similar potencies: Ki values were 1.2 nM and 3.6 nM for IM9 cells and U373 MG
      cells, respectively. Of the non-peptide antagonists, as expected, (+/-)-CP-96,345
      displayed higher affinity (0.4 nM in IM9 cells, and 1.2 nM in U373 MG cells) than
      did RP 67580 (33 nM and 223 nM in IM9 cells and U373 MG cells, respectively) in
      both cell lines. We conclude that the pharmacological profile of NK1 receptors is
      similar in the human lymphoblastoma and astrocytoma cells, i.e. if NK1 receptor
      subtypes exist in humans, these cell lines are likely to express a similar
      subtype. Because IM9 cells grow faster and are easier to maintain, this cell line
      may be preferable to the astrocytoma cells as a primary screen to identify NK1
      receptor antagonists.

PMID- 7516886
TI  - Galanin-induced membrane depolarization of neonatal rat cultured dorsal root
      ganglion cells.
AB  - In this study we examined the effects of galanin on membrane currents recorded
      from neonatal rat cultured dorsal root ganglion neurones using the whole-cell
      patch-clamp technique. When neurones were voltage-clamped at -60 mV, galanin (1
      300 nM) evoked an inward current associated with an increase in input
      conductance. These effects were observed in 21 of the 33 dorsal root ganglion
      neurones studied and were not attenuated by the galanin receptor antagonist
      galantide. Galanin fragments, galanin-(1-16) and galanin-(21-29) (300 nM) also
      elicited an inward current at -60 mV. The inward current induced by galanin was
      not linearly related to membrane potential indicating that the membrane current
      response was the result of more than one ionic event.

PMID- 7516887
TI  - Altered responses of purified blast cells from the myelodysplastic syndromes to
      colony-stimulating factors in vitro: comparison with normal blast cells.
AB  - To evaluate the effects of colony-stimulating factors (CSFs) on pathological
      cells from myelodysplastic syndromes (MDS), the blast cells from 19 MDS patients
      (eight low-risk MDS, six high-risk MDS, and five leukemic transformation of MDS
      [LT-MDS]) and four normal volunteers were successfully enriched by separating
      CD34-positive cells by the use of immunomagnetic beads, and their responsiveness
      to granulocyte or granulocyte-macrophage CSF (G-CSF or GM-CSF) was examined in
      short-term liquid suspension culture. The proliferation of MDS blast cells was
      clearly promoted by these CSFs in all cases examined, but considerable
      percentages of them often remained immature compared with the favorable
      maturation of normal blast cells, especially in the more advanced disease groups
      (LT-MDS and high-risk MDS) that included two prominent cases with a remarkable
      blast cell growth without maturation induction by CSFs. The expression of
      esterase activities was rather sluggish in the MDS cases, in contrast to normal
      expression. These data showed that MDS blast cells proliferate in response to
      CSFs but that maturation is less than that observed with normal blast cells in
      vitro. Much care should be taken with in vivo application of CSFs to high-risk
      MDS patients.

PMID- 7516888
TI  - Replication and endoreplication in developing megakaryocytes in vitro.
AB  - To study the relation in time between replication and endoreplication and the
      relation between appearance of platelet-specific proteins and endoreplication in
      maturing megakaryocytes, peripheral blood mononuclear cells highly enriched in
      hematopoietic progenitors were cultured in liquid cultures and plasma clots in
      the presence of either interleukin-3 (IL-3) and stem cell factor (SCF) or medium
      conditioned by blood mononuclear cells stimulated by phytohemagglutinin (PHA). In
      plasma clots, megakaryocytic (MK) colonies appeared first on day 5 and reached a
      maximum by day 8, whereas the number of cells per colony increased until day 10,
      indicating that there was a single wave of MK colony formation. In liquid
      cultures, the first immunologically recognizable megakaryocytes appeared on day 5
      and expressed GPIIb/IIIa and thrombospondin only, but all other platelet-specific
      protein markers appeared within 24 hours. Replating cells from liquid medium into
      plasma clots showed that 92 +/- 8% of day 6 GPIIb/IIIa-positive cells are capable
      of replicating. Their replicative potential decreased with age, however, so that
      between days 6 and 11, a linear correlation was noted between the logarithm of
      the percentage of megakaryocytes with replicative capacity and their age in
      culture. Replication ceased completely after day 10. In the presence of IL-3,
      polyploid megakaryocytes appeared at the same time that GPIIb/IIIa was expressed,
      and the megakaryocyte distribution into ploidy classes remained unchanged until
      day 20. In the presence of PHA-leukocyte conditioned medium (PHA-LCM), ploidy of
      megakaryocytes was shifted toward higher classes after day 6, and the process of
      endoreplication was completed by day 10. No changes in ploidy distribution were
      noted between days 10 and 20. These findings indicate that in the cohort of
      megakaryocytes derived from colony-forming units-megakaryocyte (CFU-MK),
      endoreplication can occur at an early stage of development, proceeds
      synchronously with replication, and is completed before the megakaryocytes
      exhaust their replicative potential.

PMID- 7516889
TI  - Evidence for internal autocrine regulation of growth in acute myeloblastic
      leukemia cells.
AB  - Blast cells from 70% of patients with acute myeloid leukemia (AML) show some
      evidence of in vitro autonomous growth, which appears to be related to the
      autocrine secretion of growth factors, particularly granulocyte-macrophage colony
      stimulating factor (GM-CSF). In the majority of cases, the growth factors appear
      to be involved in classical extracellular autocrine or paracrine loops with
      neutralizing antibodies to the relevant cytokine inhibiting growth. In a
      minority, however, antibodies do not inhibit growth despite evidence of secretion
      of the cytokine. There is evidence for intracellular autocrine loops in murine
      leukemic cell lines. In this study, we wished to investigate for the presence of
      such intracellular loops involving GM-CSF in AML blast cells. Blast cells from 11
      patients with AML were cultured in the presence of either neutralizing GM-CSF
      antibody or an antisense oligonucleotide directed against GM-CSF. We also studied
      the effect of the oligonucleotide on the autonomous growth of cells whose
      production of GM-CSF had been apparently abolished by either interleukin-1
      receptor antagonist (IL-1Ra) or following blast cell purification using the CD34
      antigen. The autonomous growth of the blast cells from nine of the 11 patients
      was inhibited by the antisense oligonucleotide (but not by the control sense
      oligonucleotide). However, only six of the nine were inhibited by the anti-GM-CSF
      antibody. Similarly, in one patient whose CD34 purified blast cells continued to
      show a high degree of autonomous growth but did not produce detectable GM-CSF,
      growth was inhibited by the antisense oligonucleotide but not by antibody, while
      in another patient whose cells were inhibited by IL-1Ra with, again, loss of
      detectable GM-CSF, growth could be further inhibited by the addition of the
      oligonucleotide but not the antibody. These studies provide evidence that
      intracellular autocrine loops involving GM-CSF are involved in the autonomous
      growth of some AML blast cells.

PMID- 7516891
TI  - GABAergic boutons establish synaptic contacts with the soma and dendrites of
      cuneothalamic relay neurons in the rat cuneate nucleus.
AB  - This study investigates the synaptic relation between gamma-aminobutyric acid
      immunoreactive (GABA-IR) and cuneothalamic relay neurons (CTNs) in the rat
      cuneate nucleus. Retrograde transport of wheat germ agglutinin conjugated with
      horseradish peroxidase complex (WGA-HRP) was used to label CTNs while anti-GABA
      immunogold serum was used for the detection of GABA-IR boutons associated with
      CTNs. With these procedures, immunogold-labelled GABA-IR boutons were found to
      form axosomatic, axodendritic and axospinous synapses with the WGA-HRP-labelled
      but immunonegative CTNs. Quantitative estimation showed that the mean ratios of
      GABA-IR to GABA-immunonegative boutons making synaptic contacts with somata,
      proximal dendrites, and distal dendrites were 47.9%, 49.1% and 34.7%,
      respectively. Statistical analysis showed that the incidence of GABA-IR boutons
      on the somata and proximal dendrites of CTNs was significantly higher than on the
      distal dendrites. Our results indicate that GABA is the primary inhibitory
      neurotransmitter in the cuneate nucleus, thereby emphasizing the importance of
      postsynaptic inhibition on cuneothalamic relay neurons.

PMID- 7516890
TI  - The high affinity Fc gamma receptor (CD64) induces phagocytosis in the absence of
      its cytoplasmic domain: the gamma subunit of Fc gamma RIIIA imparts phagocytic
      function to Fc gamma RI.
AB  - The high affinity Fc gamma receptor, Fc gamma RI, is unique among the three
      classes of macrophage Fc gamma receptors not only in its affinity for IgG, but
      also in the structure of its cytoplasmic domain. Fc gamma RIIA and the gamma
      subunit of Fc gamma RIIIA have tyrosine-containing motifs within their
      cytoplasmic domains that are phosphorylated when crosslinked and that are
      required for phagocytosis by COS-1 cell transfectants. In contrast to these other
      Fc gamma receptors, Fc gamma RI does not contain cytoplasmic tyrosines and does
      not induce phagocytosis in COS-1 transfectants. We transfected wild-type (WT) and
      mutant (MT) Fc gamma RI lacking the cytoplasmic domain into COS-1 cells and
      murine macrophages and assessed phagocytosis using IgG-coated red blood cells
      (RBCs) and RBCs conjugated with Fab anti-human Fc gamma RI monoclonal antibody
      (mAb). Fc gamma RI, in contrast to Fc gamma RIIA, did not induce phagocytosis in
      COS cells. However, both WT and MT Fc gamma RI induced phagocytosis in murine
      macrophages, and phagocytosis was inhibited by the tyrosine kinase inhibitor
      tyrphostin 23. Human monocytes also phagocytosed Fc gamma RI-targeted RBCs, and
      activation of Fc gamma RI on monocytes with Fab anti-Fc gamma RI induced
      phosphorylation of Fc gamma RII on tyrosine residues. However, Fc gamma RI
      activation of Fc gamma RI-Fc gamma RIIA COS-1 cotransfectants did not induce
      tyrosine phosphorylation of Fc gamma RIIA, and coexpression of Fc gamma RI and Fc
      gamma RIIA in COS cells did not confer Fc gamma RI phagocytic capability. In
      contrast, coexpression in COS-1 cells of Fc gamma RI with the gamma subunit of Fc
      gamma RIIIA conferred phagocytic function to both Fc gamma RI and the MT Fc gamma
      RI lacking the cytoplasmic domain. Thus, Fc gamma RI does not require its
      cytoplasmic domain to mediate a phagocytic signal and interacts with the gamma
      subunit of Fc gamma RIIIA to induce phagocytosis.

PMID- 7516893
TI  - Treatment by human recombinant soluble TNF receptor of pulmonary fibrosis induced
      by bleomycin or silica in mice.
AB  - Intratracheal instillation of bleomycin (0.08 U) or silica (2 mg) to mice leads,
      after 15 days, to a patchy pulmonary fibrosis associated with a significant
      increase of the lung hydroxyproline. Since tumour necrosis factor (TNF) seems to
      be an important mediator in pulmonary fibrosis, we wondered whether this fibrosis
      might be prevented by a new TNF-alpha antagonist. Infusion of a 55 kD human
      recombinant soluble TNF receptor rsTNFR-beta, at a rate of 20 micrograms.day-1,
      prevented the bleomycin/silica induced increase of lung hydroxyproline content,
      as measured 15 days after instillation. Infusion of rsTNFR-beta was also
      effective in the treatment of an established fibrosis, i.e. administered 25 or
      more days after instillation of bleomycin or silica, since it reduced lung
      collagen content. Recombinant soluble TNFR-beta had no significant influence on
      the number of cells, mostly macrophages, recovered by bronchoalveolar lavage. The
      examination of histological sections indicated that the rsTNFR-beta reduced the
      proportion of areas of damaged lung and, in silicosis, the formation of nodules
      with a rich collagen content. This study suggests that rsTNFR-beta might be
      useful in the therapy of pulmonary fibrosis.

PMID- 7516894
TI  - Acetylcholine receptors of the Drosophila brain: a 900 bp promoter fragment
      contains the essential information for specific expression of the ard gene in
      vivo.
AB  - The ard gene encodes a beta-subunit of Drosophila nicotinic acetylcholine
      receptors specifically expressed in a subset of neurons. To identify the cis
      regulatory region responsible for this cell-specific expression, various 5'
      fragments of the ard gene were fused to a lacZ reporter gene and introduced into
      the Drosophila genome. A DNA fragment spanning approximately 760 bp upstream and
      approximately 140 bp downstream of a cluster of putative transcription start
      sites produced a pattern of beta-galactosidase activity that resembles the
      distribution of ARD transcripts. Both in embryos and adults the levels of lacZ
      RNA were similar to those of endogenous ARD transcripts, suggesting that the 900
      bp fragment harbors all essential elements for proper expression of the ard gene.

PMID- 7516892
TI  - A functional role for nitric oxide in locus coeruleus: immunohistochemical and
      electrophysiological studies.
AB  - Immunohistochemical analysis of the localization of nitric oxide synthase-(NOS)
      like immunoreactivity revealed the presence of this enzyme in a few neuronal cell
      bodies and in dendritic and axonal processes within the rat locus coeruleus (LC).
      Also cells in the pericoeruleus area were NOS-positive. Intracellular recordings
      were made from LC neurons in brain slices. Bath application of the NOS inhibitors
      nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMMA)
      potently enhanced the excitatory postsynaptic potential (EPSP) evoked by focal
      electrical stimulation of the slice. Hemoglobin, which binds extracellular NO,
      also enhanced the EPSP. This enhancement was reversed by coadministration of L
      arginine, a precursor of neuronal nitric oxide (NO). Neither NOS inhibitors, L
      arginine, nor hemoglobin had effects on the resting membrane potential or
      impedance. These results suggest a role for NO in synaptic transmission in the
      LC.

PMID- 7516895
TI  - Inhibition of rat mast cell protease 1 by vitronectin.
AB  - Rat mast cell protease 1 (RMCP-1) is a chymotrypsin-like serine protease
      specifically expressed by connective tissue-type mast cells. The enzyme is stored
      in the secretory granules in a macromolecular complex with heparin proteoglycan.
      In the present investigation it was shown that RMCP-1 is inhibited by vitronectin
      (VN), an RGD-containing adhesive glycoprotein with heparin-binding properties.
      RMCP-1 that had been separated from heparin proteoglycan was less susceptible to
      inhibition than RMCP-1 present in complex with heparin proteoglycan. Pre
      incubation of VN with purified heparin partially blocked the RMCP-1 inhibiting
      activity of VN. Plasma VN had negligible RMCP-1-inhibiting activity. However,
      heat treatment of plasma VN, which is known to expose the heparin-binding domain,
      induced RMCP-1-inhibiting activity. Affinity chromatography on immobilized VN
      showed that RMCP-1 bound with high affinity to VN. The binding of RMCP-1 to VN
      was not heparin-dependent since free RMCP-1 bound with equal affinity to the
      immobilized VN as RMCP-1 present in complex with heparin. The inhibition of RMCP
      1 by VN was shown to be reversible.

PMID- 7516896
TI  - The lamin B receptor-associated protein p34 shares sequence homology and
      antigenic determinants with the splicing factor 2-associated protein p32.
AB  - The lamin B receptor (p58) is an inner nuclear membrane protein that forms an in
      vivo complex with the nuclear lamins, a nuclear envelope kinase, and two other
      nuclear proteins with apparent M(r) of 18,000 (p18) and 34,000 (p34). We now
      report the isolation of p34 by partial dissociation of the immunoaffinity
      purified p58 protein complex. Determination of the N-terminal amino acid sequence
      of purified p34 shows that this polypeptide is homologous to p32, a splicing
      factor 2 (SF2)-associated protein. The relatedness between p34 and p32 can be
      further established by showing that antibodies raised against N- and C-terminal
      peptides of p32 cross-react with purified p34. As the amino acid sequence of p58
      contains an arginine/serine (RS)-rich region similar to the RS-rich region found
      in SF 2, we speculate that these domains provide binding sites for p34 and that
      this protein may be a linker between the nuclear membrane and intranuclear
      spliceosomal substructures.

PMID- 7516897
TI  - Identification of the GABAA receptor subtype mRNA in human pancreatic tissue.
AB  - Evidence suggests a physiological role of the GABAA receptor in the pancreas.
      Clinically, an autoimmune reaction involving the GABA biosynthesizing enzyme,
      glutamic acid decarboxylase has been implicated in the development of insulin
      dependent diabetes mellitus. To determine the subtypes of GABAA receptor
      expressed in human pancreas, we analyzed, with the use of the reverse
      transcription/polymerase chain reaction technique human pancreatic tissue for the
      presence of GABAA receptor subunits alpha 1-6, beta 1-3, and gamma 1-2
      transcripts. Unlike brain tissue, pancreatic tissue only expresses the alpha 2,
      beta 3 and gamma 1 subunits. Our results provide evidence of a specific GABAA
      receptor subtype expressed in human pancreatic tissue.

PMID- 7516898
TI  - Functional regulation of the human integrin VLA-1 (CD49a/CD29) by divalent
      cations and stimulatory beta 1 antibodies.
AB  - We have investigated the regulation by divalent cations Mg2+, Ca2+ and Mn2+ of
      the functional activity of the human integrin VLA-1 expressed on neuroblastoma
      NB100 cells. VLA-1-mediated adhesion of NB100 cells to ligand collagen type I was
      supported by either mM concentrations of extracellular Mg2+ or microM levels of
      Mn2+. In contrast, Ca2+ alone did not induce activation of VLA-1 but exerted a
      potent inhibitory effect on the Mg(2+)-supported cell adhesion. We have also
      demonstrated that VLA-1 can be directly activated by the stimulatory monoclonal
      antibody TS2/16 specific for the integrin beta 1 subunit, resulting in effective
      adhesion of NB100 cells to type I collagen. This study has been possible by using
      a novel blocking VLA-alpha 1 specific monoclonal antibody, 5E8D9.

PMID- 7516899
TI  - Tyrosine phosphorylation and stimulation of protein kinase C delta from porcine
      spleen by src in vitro. Dependence on the activated state of protein kinase C
      delta.
AB  - Native protein kinase C delta from porcine spleen is phosphorylated in vitro by
      the tyrosine kinase src and to a much smaller extent by fyn. The tyrosine
      phosphorylation of PKC delta is restricted to the activated state of the enzyme,
      i.e. it occurs only in the presence of an activator, such as TPA or bryostatin.
      Upon phosphorylation at tyrosine, the apparent molecular weight of PKC delta
      increases by 6 kDa. Phosphorylation by src induces a stimulation of PKC delta
      activity apparently exhibiting some substrate selectivity. Other PKC isoenzymes,
      such as cPKC (alpha, beta, gamma), are not phosphorylated by src or only to a
      very small extent. This phosphorylation is not dependent on TPA and does not
      cause an increase in activity and molecular weight of the enzyme.

PMID- 7516900
TI  - Iloprost reduces leukocyte adhesion in skeletal muscle venules following
      ischaemia in a rat model of femorodistal bypass.
AB  - Intraarterial bolus treatment with the prostacyclin analogue iloprost appears to
      have a prolonged beneficial effect on femorodistal bypass graft flow which
      extends beyond the duration of its vasodilator properties. The effect of iloprost
      on the microcirculation rendered ischaemic over the time course of a distal
      bypass operation was investigated in this study without the use of fluorescent
      light. METHODS: A rat model was designed to allow prolonged direct observation of
      leukocyte-venular endothelial adhesion in a femorodistal bypass simulation. The
      extensor digitorum longus (EDL) muscle of 10 rats was subjected to two 30 minute
      periods of ischaemia by a non-venous occluding tourniquet and to simulate some of
      the changes of chronic ischaemia the adverse effect of ischaemia was accentuated
      by indirect electrical stimulation via the lateral popliteal nerve. RESULTS:
      Intraarterial bolus treatment with iloprost significantly reduced the total
      numbers of leukocytes observed in EDL venules, and the numbers exhibiting
      evidence of adhesion by rolling or sticking to venule endothelium compared with
      saline controls at one hour post ischaemia. Ischaemia induced vasodilatation and
      reduced shear stress by a similar and significant amount in both groups.
      CONCLUSION: Two periods of ischaemia and reperfusion similar to those which occur
      during bypass grafting resulted in changes in the distal microcirculation
      consistent with reperfusion injury. Intraarterial bolus treatment with iloprost
      prevented these leucocyte-endothelial changes. It appears iloprost may have a
      role in reducing leukocyte-induced reperfusion injury in femorodistal bypass
      surgery.

PMID- 7516901
TI  - T lymphocyte effector mechanisms in the retina in posterior uveitis.
AB  - Loss of vision in posterior uveitis is often the consequence of chronic retinal
      oedema and immune-mediated damage to the retinal parenchyma. Research in other
      putative autoimmune diseases such as rheumatoid arthritis, and in animal models
      of autoimmune disease, has uncovered a number of mechanisms which may contribute
      to the development of inflammatory disease within the eye. With recent
      developments in specific anti-cytokine therapy an understanding of these
      mechanisms, most of which are cytokine-mediated, is essential in order to plan
      more effective therapeutic strategies. In this paper we review recent research
      investigating the functional characteristics of the T cells which are recruited
      into the retina in experimental autoimmune uveoretinitis, including activation
      status, antigen-specific proliferation in vitro and cytokine mRNA production in
      the inflamed retina.

PMID- 7516902
TI  - [Role of hepatitis C virus in the genesis of hepatic lesions observed in
      alcoholic patients with liver cirrhosis].
AB  - The aim of study was to assess the role of hepatitis C virus (HCV) infection in
      164 alcoholic cirrhotic patients. We studied the prevalence of anti-HCV
      antibodies using ELISA and RIBA first and second generation tests. Twenty-two %
      of the patients had anti-HCV antibodies detected by ELISA 2, RIBA 2 test was
      positive in 10% of the patients and indeterminate in 3%. We compared
      epidemiological, biological and histological characteristics according to the
      results of the tests. By comparing ELISA 2-RIBA 2 positive patients to ELISA 2
      negative patients, we observed, in the former, a) a higher serum aminotransferase
      activity, b) a lower serum gammaglutamyl transpeptidase activity, and c) a lower
      histological score of alcoholic hepatitis. In addition, in a group of ELISA 2
      positive RIBA 2 negative patients, the values were intermediate between those of
      the two former groups. However, most of these patients had a negative third
      generation ELISA test. The whole results suggest that HCV is likely to play a
      role in the pathogenesis of liver damage in a high number of alcoholic cirrhotic
      patients.

PMID- 7516903
TI  - [Is the identification of acute biliary and alcoholic pancreatitis by early
      pancreatic enzyme assay possible?].
AB  - Early and appropriate treatment of acute pancreatitis (AP) depends on early
      causal diagnosis. Published studies have shown favourable results following
      sphincterotomy performed within the 72 hours of onset of severe gallstone
      associated AP. Among the various bio-clinical indices, the lipase/amylase (L/A)
      ratio, computed within 72 hours after onset, has been shown to discriminate
      between alcoholic and non alcoholic AP. Our study evaluates the data of
      biochemical disorders in 51 patients presenting with an episode of AP; these
      patients were divided into 3 groups: A: alcoholic AP, n = 15; B: biliary AP, n =
      25; and C: post-ERCP AP, n = 11. These 3 groups were similar with respect to
      clinical severity of AP and CT scan. The time delays between onset of the
      symptoms and the biochemical assay were 1.9 +/- 0.3, 1.9 +/- 0.2 and 0.6 +/- 0.3
      d (P < 0.01). AST, ALT, bilirubin, GGT and alkaline phosphatase were
      significantly (P < 0.05) greater in group B. Blamey's score was 0.5 +/- 0.2, 2.8
      +/- 0.2 and 2.5 +/- 0.4 in groups A, B and C respectively. Serum amylase, serum
      lipase and L/A ratio were identical in groups A and B. The decrease in serum
      amylase after 48 hours was more important only in group B (56 +/- 8, 80 +/- 4, 47
      +/- 3% respectively in groups A, B and C). L/A ratio was significantly greater in
      group C when compared with group A and B (1.7 +/- 0.4, 1.5 +/- 0.2 and 2.2 +/-
      0.3 in groups A, B and C respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516904
TI  - Endoscopic palliation of inoperable malignant dysphagia: long-term follow up.

PMID- 7516905
TI  - [Transvaginal color-coded Doppler ultrasound in ovarian tumors].
AB  - In 129 patients with ovarian tumours, a preoperative examination by transvaginal
      colour Doppler sonography (ATL UM9 HDI) was performed. 45 were malignant and 84
      benign. 46 patients were premenopausal and 83 postmenopausal. All tumour vessels
      were analysed by spectrum analysis. The number of tumour vessels and the lowest
      resistance index (RImin) and pulsatility index (PImin) of all vessels were
      evaluated as diagnostic criteria of the neovascularisation. Up to 19 vessels were
      found in 115 (89%) tumours. In benign lesions, the number of vessels was
      significantly lower than in malignancies (median 3 versus 9, p < 0.0001). The
      RImin and PImin values between benign and malignant tumours were also
      significantly different, independent of the menopausal status. In postmenopausal
      patients, the median RImin in 42 benign tumours was 0.62 (0.26-1.0) and in 41
      malignancies 0.40 (0.22-0.66). The median PImin was 0.98 (0.31-5.84) in benign
      tumours and 0.53 (0.25-1.22) in malignant tumours. However, due to the
      overlapping range between benign and malignant tumours, these parameters do not
      allow an accurate differentiation. With a cut off value for RImin = 0.5 and PImin
      = 0.7, the sensitivity is 85% or 82.5% respectively. The specificity for RImin
      and PImin is 77%, and the diagnostic accuracy is 84% and 80% respectively. The
      correlation coefficient between RImin and PImin is 0.99 in benign and malignant
      tumours and both indices are adequate. The calculation of the RI is more easily
      available and should be preferred as a diagnostic parameter.

PMID- 7516906
TI  - Characterization of Mip proteins of Legionella pneumophila.
AB  - The Mip ('macrophage infectivity potentiator') protein of Legionella pneumophila
      has been shown to be an essential virulence factor, exhibiting peptidyl-prolyl
      cis/trans isomerase (PPIase) activity that can be inhibited by the
      immunosuppressant FK506. The cloning and sequencing of mip genes from three
      different L. pneumophila strains revealed a single amino acid substitution which
      did not affect the isomerase property of the enzyme. Mip proteins isolated from
      two wild-type L. pneumophila strains and from two corresponding Escherichia coli
      K-12 recombinant clones derived from these strains exhibited identical enzymatic
      properties and the precursor proteins are processed at identical cleavage sites.
      The mature Mip proteins exist in an oligomeric form. Site-directed mutagenesis
      demonstrated that a substitution of an Asp residue at position 142 by a Leu
      residue affects PPIase activity of Mip.

PMID- 7516907
TI  - The Warthin-Starry stain in the diagnosis of small intestinal microsporidiosis in
      HIV-infected patients.
AB  - A protocol for the handling of small intestinal biopsies from HIV-infected
      patients is presented. This protocol includes the Warthin-Starry stain for the
      detection of microsporidia. This stain has proved a reliable and sensitive
      diagnostic technique for microsporidial infections as it stains both
      Enterocytozoon bieneusi and Septata intestinalis in duodenal enterocytes. Because
      the stain demonstrates Septata intestinalis in lamina propria macrophages as well
      as enterocytes, it allows for the practical differentiation of these two
      microsporidial infections. The Warthin-Starry stain has also demonstrated Septata
      intestinalis in nasal and colonic biopsies in some of these patients. Since the
      completion of an earlier study, a further 40 cases of Enterocytozoon bieneusi and
      three cases of Septata intestinalis have been diagnosed in just over 240
      consecutive duodenal biopsies from HIV positive patients presenting with
      diarrhoea and other gastrointestinal complaints. Other opportunistic infections
      include cytomegalovirus in four cases, mycobacteria in eight cases,
      cryptosporidia in nine cases, giardia in four cases and Isospora belli in one
      case. Since the ratio of these opportunistic infections has remained much the
      same as in the previous study of 180 consecutive duodenal biopsies, we suggest
      that these rates may reflect the actual prevalence of microsporidial infections
      in AIDS patients in Sydney, Australia.

PMID- 7516908
TI  - Staining of microsporidian spores by optical brighteners with remarks on the use
      of brighteners for the diagnosis of AIDS associated human microsporidioses.
AB  - Conditions for the effective fluorescence labelling of microsporidian spores by
      optical brighteners, based on the presence of chitin in the spore wall, are
      described. Spores of Vairimorpha ephestiae, V. necatrix, V. plodiae, Nosema
      bombycis, N. apis, N. algerae, Encephalitozoon cuniculi and Enterocytozoon
      bieneusi were examined. The degree of binding of Calcofluor White M2R (CFW) to
      untreated spores depends on the conditions and time of storage and the degree of
      bacterial contamination of the spore sample. Unpurified spores, stored in water
      are unreliable as control material for the estimation of CFW labelling. However,
      spores subjected to alkaline treatment by NaOH before CFW application are
      visualized with ease under all experimental conditions by their bright, not
      quenching fluorescence in shortwave light (approximately 350 nm) in CFW dilutions
      of 10(-4) or even lower. Similar improvement in labelling is achieved by exposing
      spores to CFW dissolved in 0.5-1N NaOH. As well as Calcofluor White M2R other
      optical brighteners (e.g. Uvitex 2B, Ciba-Geigy or Rylux BA, Ostacolor) can be
      used for labelling of spores.

PMID- 7516909
TI  - Molecular biological analysis of paraffin-embedded tissues.
AB  - Molecular biology techniques have been adapted to the analysis of paraffin
      embedded tissues (PETs), expanding their clinical utility. In vitro amplification
      with the polymerase chain reaction (PCR) promises to be the most useful means of
      retrospective analysis because it can be performed successfully on nucleic acids
      that have been partially degraded during fixation, paraffin embedding, and the
      extraction process. Five clinical situations in which DNA analysis of PETs can be
      helpful are: (1) confirmatory molecular diagnosis of lymphoma in which fresh
      tissue has not been obtained at the time of surgery, (2) identification of
      infectious agents, (3) genetic characterization of a putative inherited disease
      in which the affected individual has died, (4) confirmation of donor cell
      malignancy in transplant recipients, and (5) specimen identification. The role of
      the pathologist in molecular diagnosis will grow because of the feasibility of
      using PETs, a venue unique to our profession.

PMID- 7516910
TI  - Extramammary Paget's disease associated with prostate adenocarcinoma.
AB  - A case of scrotal and penile extramammary Paget's disease (EMPD) and concurrent
      prostate adenocarcinoma in a 59-year-old patient is presented.
      Immunohistochemically, the tumor cells of both the EMPD and prostate stained
      positively for prostate-specific antigen. Six previously reported cases of EMPD
      associated with prostate adenocarcinoma are reviewed, along with a discussion of
      current theories of the pathogenesis of EMPD.

PMID- 7516912
TI  - Reduced expression of apoptosis-related antigens in thymuses from patients with
      myasthenia gravis.
AB  - Expression of the apoptosis-related antigens, Fas and BM-1, in thymuses from
      patients with myasthenia gravis (MG) was examined using immunohistochemistry and
      reverse transcription-polymerase chain reaction (RT-PCR). Fas antigen was
      markedly decreased in lymphoid follicles in thymuses from patients with MG, but
      was expressed diffusely in the remaining thymus tissues and in neonatal thymuses.
      BM-1 antigen was not expressed in the lymphoid follicles or other parts of the
      thymus. Fas mRNA was also decreased to various degrees in the thymuses from MG
      patients. Therefore, Fas antigen may play an important role in autoimmune
      diseases including MG.

PMID- 7516911
TI  - Cross-linking of a sequential epitope within the beta-chain of HLA-DR/DP
      molecules suppressing B lymphocyte growth and inducing homotypic cell
      aggregation.
AB  - A monoclonal antibody (SU2) directed against HLA class II antigens has been
      produced by immunizing BALB/c mice with a lymphoblastoid cell line, RPMI-8866
      cells. The specificity of this mAb has been determined using a panel of HLA class
      II transfectants. SU2 stained all HLA-DR and HLA-DP transfectants tested, but
      reacted with only one HLA-DQ (HLA-DQw2). From comparison of the available data
      sequences of known HLA class II molecules, it appeared that the epitope
      recognized by the SU2 mAb contains a sequence of 6 amino acids (DSDVGE) at
      position 41-46 of the beta-chain of HLA-DR/DP. Functional studies indicated that
      SU2 mAb strongly induced cell aggregation and large clumping in resting tonsillar
      B cells. SU2 mAb inhibited the spontaneous growth and proliferation of B
      lymphoblastoid cell lines and drastically inhibited [3H]thymidine uptake by
      phorbol 12-myristate 13-acetate (PMA)-activated resting B cell. Results are
      discussed in relation to the dual recognition of HLA-DR/DP by SU2 mAb.

PMID- 7516913
TI  - Binding of human beta 2-microglobulin to murine EL4 thymoma cells upregulates MHC
      class I heavy-chain epitopes, inhibits IL-2 secretion and induces resistance to
      killing by natural killer cells.
AB  - A variety of murine tumor cell lines was studied for its binding of exogeneously
      added human beta 2-microglobulin (h beta 2m). Three T lymphomas and one IL-2
      dependent T-cell line (HT-1) bound substantial amounts of h beta 2m, whereas P815
      mastocytoma cells, an Abelson virus-infected pre-B cell line (ABLS-8), X63 B
      lymphoma cells and YAC cells did not bind h beta 2m. In two of the T lymphomas,
      EL4 and BW5147, binding of h beta 2m led to an increase in major
      histocompatibility complex class I (MHC-I) heavy-chain epitope expression as
      measured by anti-H-2K/D antibody binding and FACS analysis. EL4 cells which had
      bound h beta 2m decreased their rate of constitutive IL-2 secretion and became
      resistant to activated natural killer (NK) cell killing. The present data suggest
      the binding of h beta 2m to mouse T cells leads to conformational changes of MHC
      I heavy chains which influence both effector and target functions of the cell.

PMID- 7516914
TI  - Potentiation of GM-CSF or G-CSF induced mobilization of circulating progenitor
      cells by pretreatment with IL-3 and harvest by apheresis.
AB  - Recombinant human colony-stimulating factors (CSFs) are increasingly used for
      mobilizing progenitor cells in the peripheral blood (PB). 7 patients were treated
      with GM-CSF or G-CSF at a dose of 5 micrograms/kg/d for 5 days and after a
      treatment free interval received another cycle of the same cytokine after
      pretreatment with IL-3. Pretreatment with 5 micrograms/kg/d of IL-3 for 7 days
      did not mobilize by itself but significantly potentiated GM-CSF or G-CSF induced
      mobilization of PB progenitor cells in all 5 patients tested. As compared to the
      mobilization capacity of GM-CSF or G-CSF alone, 7 day IL-3 pretreatment
      potentiated maximum values of CFU-GM by 3.7-6.3 fold in patients receiving GM-CSF
      (n = 2) and by 1.8-3.3 fold in patients receiving G-CSF leading to a 10-23 fold
      increase in numbers of circulating CFU-GM by the combination IL-3/GM-CSF, and a
      26-101 fold increase by IL-3/G-CSF, respectively. Stem cell apheresis in patients
      treated with IL-3 + G-CSF or GM-CSF yielded enough PB-stem cells to ensure
      complete engraftment after ablative chemotherapy.

PMID- 7516915
TI  - Cyclophosphamide 4 g/m2 plus rhG-CSF for mobilization of circulating progenitor
      cells in malignant lymphomas.
AB  - We report the preliminary results of a study exploring the possibility of
      collecting circulating progenitor cells (PBSC) with a protocol based on the
      administration of single doses (4 g/m2) of cyclophosphamide and G-CSF (5 or 10
      micrograms/kg) in 9 patients with non Hodgkin's lymphoma. The peak level of CD34+
      cells occurred after a median of 10 days (range 8-11), generally coinciding with
      the median peak level of CFU-GM, with a mean 31.27 fold increase above basal
      levels. 3 (range 2-5) leukaphereses were required to harvest a median number of
      25.1 x 10(4)/kg (8-105) CFU-GM and of 9.4 x 10(6)/kg (1.2-25) CD34+ cells. No
      difference was recorded between 5 and 10 micrograms/kg of G-CSF in terms of PBSC
      yield. In transplanted patients, a strong correlation was found between CD34+
      cells infused/kg and platelet recovery (r = -0.8, p = 0.002). No toxicity was
      observed and apheretic procedures were regularly performed outpatiently. Our
      conclusion is that this protocol is particularly suitable for an outpatient
      treatment/collection program.

PMID- 7516916
TI  - Clinical application of growth factors for collection of circulating
      hematopoietic progenitors in breast cancer patients treated with high-dose
      cyclophosphamide.
AB  - Seventy-seven (68 operable breast cancer with > 9 metastatic axillary nodes and 9
      inflammatory breast cancer) entered this study. During hematopoietic recovery
      after cancer therapy with high-dose cyclophosphamide (7 g/m2; HD-CTX) circulating
      hematopoietic progenitors were collected by leukapheresis (LK) in all patients
      and then cryopreserved for autologous transplantation. Following HD-CTX, 70
      patients were treated with hematopoietic growth factor(s) for 14 days: 38 with
      rhGM-CSF (group a), 16 with rhIL-3 (group b), 11 with sequential rhIL-3 and rhGM
      CSF (group c), 5 with sequential rhIL-3 and rhG-CSF (group d). Seven control
      patients (group e) did not receive any growth factor. Leukaphereses, carried out
      over 2-4 consecutive days per patient, were started earlier in group c and in
      group d patients (mean day: +12 after HD-CTX). The sequential administration of
      rhIL-3 and rhG-CSF (group d) resulted in clearly higher yield of CFU-GM and CD34+
      cells per leukapheresis (65.9 x 10(4)/Kg versus 20.9 x 10(6)/Kg, respectively) if
      compared with other groups of treatment.

PMID- 7516917
TI  - Treatment of multiple myeloma with autologous blood stem cell transplantation.
      Preliminary results of an Italian multicentric pilot study.
AB  - Starting from May, 1991, 35 untreated myeloma patients entered a multicentric
      pilot study to evaluate the feasibility of a program of PBSC transplantation for
      previously untreated myeloma patients. The schedule was as follows: 2 cycles of
      VAD followed by CY, 7 g/mq+G-CSF (Granulokine, Roche) for 14 days, to increase
      and collect PBSC. The subsequent conditioning regimen was Melphalan+Busulfan
      followed by G-CSF. As maintenance R alpha-2 IFN was given, until relapse. The
      median follow-up is 14 months (4-22). On April 1993, 34 patients received at
      least 2 cycles of VAD, 27 were submitted to PBSC collection, 22 received
      conditioning regimen plus PBSC and 16 of them are in the maintenance treatment
      with IFN. Considering 28 patients for an intention to treat evaluation (35-7 in
      treatment), responding patients are 71% with 46% who achieved CR. White cells and
      platelets raised to > 1000/mmc and > 50,000/mmc after a median period of 10 and
      13 days, from CY, and 11 and 14 days from transplant, respectively. Two patients
      relapsed, 2 others died while in PR because of CMV epatitis and candida
      pneumonia. The median number of CD34+ cells and CFU-GM was 24.75 x 10(6)/kg b.w.
      and 28.1 x 10(4)/kg b.w. respectively. In conclusion this treatment seems to be
      feasible and with low toxicity, but a longer follow-up is needed to evaluate the
      progression free survival of the high proportion of responding patients that we
      observed.

PMID- 7516918
TI  - PBSC collection after high dose chemotherapy followed by G-CSF in patients with
      malignancies: analysis of results regarding factors affecting the yield of
      hemopoietic progenitors.
AB  - High-dose non ablative chemotherapy followed by growth factors efficiently
      mobilizes and amplifies Peripheral Blood stem Cells (PBSC). Cytofluorimetric PBSC
      monitoring reduces the number of leukapheresis needed to collect sufficient
      amounts of progenitors to restore hemopoiesis after myeloablative therapy. Twenty
      eight patients, affected by lymphoproliferative disorders, were primed with non
      myeloablative chemotherapy followed by G-CSF 5 micrograms/kg/die subcutaneously,
      until leukapheresis. A total number of 90 leukaphereses was performed (median: 3
      per patient) using blood cell separator CS 3000 Plus Baxter; we collected 1 +/-
      0.8 x 10(8)/kg mononuclear cells (MNC), 6 +/- 9 x 10(4)/kg CFU-GM and 4 +/- 5 x
      10(6) CD34+ cells for each procedure. The statistical analysis showed that the
      number of progenitors collected was dependent on the age, number and type of
      previous chemotherapies and interval between the last chemotherapy and the
      priming; the type of priming, type and status of disease, sex, and bone marrow
      involvement were not significant. Duration of neutropenia after megachemotherapy
      was very short; in two cases platelet support was necessary and only two patients
      needed hospitalization. Our experience shows that high-dose non ablative
      chemotherapy followed by G-CSF is safe and yields large amounts of PBSC; several
      factors influence the quality of collections mainly regarding age and the
      previous treatment.

PMID- 7516920
TI  - Quantization of CD34+ peripheral blood hematopoietic progenitors for autografting
      in cancer patients.
AB  - After myeloablative regimens, combined reinfusion of peripheral blood
      hematopoietic circulating progenitor cells (CPC) and bone marrow, yields a very
      rapid hematopoietic recovery. Therefore, based on the knowledge that CPC express
      the CD34 and CD33 differentiation antigen, we have developed a direct
      immunofluorescence flow cytometry assay to detect the peak of CPC in the
      peripheral blood of patients treated with high dose chemotherapy and growth
      factors. This assay, compared to CFU-GM assay, has the following advantages: 1)
      easy to do 2) standardized method 3) real time information on CPC number. This
      work illustrates the practical aspects of this assay and substantiate the
      widespread use of the CD34/33 flow cytometry assay to guide harvesting of
      circulating hematopoietic progenitors for autologous transplantation.

PMID- 7516919
TI  - Peripheral blood stem cell (PBSC) mobilization and transplantation (PSCT) in
      patients with malignant lymphomas and solid tumors.
AB  - Peripheral blood stem cells can reconstitute bone marrow function after high-dose
      chemo-/radiotherapy. We describe 44 patients related with a three-day course of
      chemotherapy, for hematopoietic stem cell mobilization, consisting of
      cyclophosphamide or ifosfamide and etoposide (malignant lymphoma and germ cell
      tumor) or a one-day course of 5-fluorouracil, epirubicin and cyclophosphamide
      (breast cancer), followed by the administration of recombinant human granulocyte
      colony-stimulating factor (G-CSF). Maximum numbers peripheral blood stem cells
      (PBSC) were recruited on day 9-10 of the G-CSF administration. The total number
      of PBSC cells harvested with median 3.6 leukaphereses was 46 x 10(4)/kg (7.5-136)
      CFU-GM or 8 x 10(6)/kg (0.7-25.0)CD34+ cells for patients with solid tumors and
      26 (4.5-258) CFU-GM's or 6.1 (1-0-39.2) CD34+ cells for patients with malignant
      lymphomas. Thirty-five patients with malignant lymphomas or solid tumors received
      high-dose chemotherapy followed by bone marrow and PBSC infusion (n = 8) or PBSC
      cell infusion alone (n = 27). The recovery of granulocytes, platelets and
      reticulocytes after peripheral stem cell transplantation (-PSCT) in addition to
      or instead of bone marrow, was markedly accelerated compared with the infusion of
      BM alone. The accelerated haemopoietic recovery was associated with a reduction
      in platelet and red blood cell transfusion, reduction in fever periods and
      earlier discharge from hospital. PSCT is an important alternative to autologous
      bone marrow transplantation (ABMT). This transplantation technique may also
      allows application of multiple-cycle intensive chemotherapy.

PMID- 7516921
TI  - Peripheral blood cell harvests yield primitive multilineage progenitor cells in
      the CD34+/33- fraction.
AB  - The presence of primitive hematopoietic progenitor cells or stem cells in
      peripheral blood (PBSC's) harvests was investigated in a single cell culturing
      assay and compared with the results obtained in aspirates of normal bone marrow.
      Based on the presence of CD33, rather differentiated progenitor cells (CD34+/33+)
      were distinguished from more primitive cells (CD34+/33-). The growth potential of
      CD34+/33+ and CD34+/33- cells have been studied. Single cell sorting was
      performed from peripheral blood harvests, obtained from three patients with
      multiple myeloma during hematopoietic recovery after treatment with high dose
      cyclophosphamide and rhu-GM-CSF. To test the effect of "stem cell recruiting
      factors" the cells were sorted in 96-well plates, prefilled with liquid medium
      both in the presence of IL-3 + G-CSF+GM-CSF+Epo and the same growth factors
      supplemented with SCF+IL-6. Addition of SCF and IL-6 to the culturing medium
      enhanced the plating efficiency of CD34+/33- cells considerably more than that of
      CD34+/33+ cells. This was observed in harvests of peripheral blood as well as in
      aspirates of normal bone marrow. The differences between CD34+/33+ and CD34+/33-
      were even more pronounced when only the large colonies (> 500 cells/well) were
      taken into consideration. Assuming that IL-6 and SCF are "stem cell recruiting
      factors," the CD34+/33- fraction contains more clonogenic cells than the
      CD34+/33+ fraction. In all three patients the first CD34+ cells appearing in the
      peripheral blood (PB) after cytoreductive treatment were predominantly CD34+/33-
      (> 80%). At later stages when the leukocyte counts had reached higher values the
      CD34+/33+ cells predominated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516922
TI  - In vitro expansion of CD34+ cells mobilized with chemotherapy and G-CSF.
AB  - Hemopoietic CD34+ progenitors were isolated by immunomagnetic method from normal
      bone marrow (BM) or from peripheral blood (PB) of patients with non-Hodgkin's
      lymphoma treated with chemotherapy and granulocyte colony-stimulating factor
      (GCSF). Aliquots were seeded in long-term cultures (LTC) on bone marrow-derived
      stromal layers; non-adherent and adherent clonogenic content of the cultures was
      assayed weekly. The final recovery and the clonogenic efficiency of the CD34+
      cells were slightly higher in PB samples than in BM controls. In long term
      cultures PB cells sustained hemopoiesis as much as BM cells; at week 3 and 4 PB
      total mononuclear cells and CD34+ cells showed a non-adherent cell recovery
      higher than the respective BM controls. Furthermore, PB CD34+ cells were expanded
      in liquid culture in the presence of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) or G-CSF alone or combined with interleukin 3 (IL3), stem cell
      factor (SCF), interleukin 1 (IL1), interleukin 6 (IL6). The combination of GM
      CSF, IL3, SCF, IL1 and IL6 produced the maximum increase of both mononuclear
      cells (30-fold) and granulocyte-macrophage colony forming units (CFU-GM) (4.6
      fold) after 7 days of cultures; yet after 14 days a strong decrease of the CFU-GM
      occurred. These data suggest that G-CSF following chemotherapy mobilizes both
      early and committed hemopoietic progenitors.

PMID- 7516923
TI  - CD34+ cell selection: focus on immunomagnetic beads and chymopapain.
AB  - The aim of the present study was to develop immunoadsorption techniques for
      purifying CD34+ cells from the peripheral blood (PB) and the bone marrow (BM).
      First, we compared two methods for isolating CD34+ cells from patients with acute
      non-lymphocytic leukemia. Twenty-two samples (17 PB, 5 BM) were obtained from 19
      patients, were density cut and, after incubation with My10 antibody, were
      separated by panning or by immunomagnetic beads. Beads allowed a significantly
      better separation, either in terms of purification of CD34+ cells (85.5% +/-
      11.1% vs 55.7 +/- 23.8%, p = 0.003) or in terms of depletion of CD34+ cells from
      the negative fractions (3.9 +/- 7.6 vs 30.9 +/- 25.1%, p = 0.008). In a second
      study, 2 BMs from healthy subjects and 1 BM and 2 PBs from chronic myeloid
      leukemia patients were separated using immunomagnetic beads. The results
      confirmed the previous study the overall frequency of CD34+ cells in the isolated
      positive fractions was 85.0 +/- 10.6% (with a recovery of 64.0 +/- 5.7%), while
      it was only 2.7 +/- 6.6% in the negative fractions. In particular the purity in
      the two normal BMs was respectively 86 and 97%. According to these results, the
      great majority of clonogenic cells was separated in the CD34+ fractions.
      Chymopapain, that was used to detach the beads from the cells, was shown to be
      non-toxic to the clonogenic cells. Positive selection of CD34+ cells with
      immunomagnetic beads and chymopapain is a useful method for isolating almost pure
      progenitors from the PB and the BM for experimental use and is under
      investigation for clinical applications.

PMID- 7516924
TI  - A novel strategy of c-myc oncogene in NK activity regulation not related to the
      W6/32 MHC class-I epitope.
AB  - The c-myc gene encodes a nuclear protein whose precise function is still not
      fully understood. Introduction of a c-myc gene into a number of cell lines leads
      to an increase in their susceptibility to NK-cell lysis. It was reported earlier
      that c-myc can induce a decrease in the membrane expression of the MHC class-I
      molecules and this may be one of the factors that render target cells relatively
      more susceptible to NK lysis. In this contribution, we show, in a human LCL line
      transfected with a constitutively active c-myc gene, an increased sensitivity to
      NK lysis, which correlates with an augmented effector-target binding ability of c
      myc-transfected LCLs and with a high ICAM-I expression rather than with down
      regulation of MHC class-I W6/32 epitope expression.

PMID- 7516927
TI  - Regulation of ICAM-1 (CD54) expression in human breast cancer cell lines by
      interleukin 6 and fibroblast-derived factors.
AB  - Four human breast cancer cell lines (T47D, ZR-75-1, MCF7D and HS578T) were
      examined for the effects of cytokines on expression of cell surface antigens.
      Interferon (IFN)gamma up-regulated the expression of ICAM-I (CD54) in all the
      cell lines and coordinately up-regulated both CD54 and CD40 expression in T47D.
      Tumour necrosis factor (TNF)alpha, interleukin (IL)1 alpha, IL1 beta and IL6 also
      up-regulated the expression of CD54 in all the cell lines but CD40 was
      unaffected. Levels of expression of CD11a, CD18, CD49b, CD58 and CD71 were
      unaltered by these cytokines. Conditioned medium (CM) generated from human
      fibroblasts, and in particular from foetal cells, was highly effective in up
      regulating expression of ICAM-1 but not of CD40 in the breast cancer cell lines.
      ICAM-1 induction correlated with IL6 bioactivity in these CMs. Combinations of
      IL6 with other cytokines, such as IL1, resulted in further increases in ICAM-1
      expression. Our observations suggest that IL6 is involved in intercellular
      signalling between mesenchyme and breast cancer epithelium.

PMID- 7516925
TI  - Increased production of immune activation marker neopterin by colony-stimulating
      factors in gynecological cancer patients.
AB  - Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) have recently been introduced in the treatment of
      chemotherapy-induced neutropenia. Effects of these CSFs on the cellular immune
      system were evaluated in 38 neutropenic gynecological cancer patients during
      chemotherapy. In addition to restoring the leukocyte count, GM-CSF--to a greater
      extent than G-CSF--also induced neopterin, a sensitive marker of macrophages
      activated by interferons. This effect was confirmed in vitro by investigating the
      effects of these CSFs on interferon-gamma-mediated pathways in THP-I human
      myelomonocytic cells. The results suggest activation of immune effector cells by
      GM-CSF.

PMID- 7516926
TI  - Melanoma-specific CD4+ T lymphocytes recognize human melanoma antigens processed
      and presented by Epstein-Barr virus-transformed B cells.
AB  - While much emphasis has been placed on the role of MHC class I-restricted CD8+ T
      cells in the recognition of tumor-specific antigens (Ag), evidence has
      accumulated that CD4+ T cells also play a critical role in the anti-tumor immune
      response. However, little information exists on the nature of MHC class II
      restricted human tumor Ag. In an attempt to develop in vitro systems to
      characterize such Ag, we examined the ability of Epstein-Barr virus (EBV)
      transformed B cells to present melanoma-associated Ag to melanoma-specific CD4+
      cells. CD4+ T cells cultured from lymphocytes infiltrating a s.c. melanoma
      metastasis secreted TNF-alpha and GM-CSF specifically in response to autologous
      cultured melanoma cells expressing MHC class II molecules. These CD4+ cells also
      recognized MHC class II-compatible EBV-B cells pulsed with extracts of autologous
      melanoma cells, but failed to recognize EBV-B cells pulsed with autologous non
      transformed cells or a variety of allogeneic tumors or normal cells. B cells pre
      fixed with paraformaldehyde were incapable of Ag presentation, suggesting that
      intracellular processing events were occurring. Antibody-blocking studies defined
      HLA-DR as the dominant if not exclusive restriction locus in this T-B
      interaction, and HLA-DR genotyping revealed DRBI*0404 to be the probable
      restriction element. In a second patient, a CD4+ T-cell clone cultured from a
      melanoma lesion recognized autologous tumor Ag presented by autologous EBV-B; no
      corss-reactivity was observed with the other tumor system investigated, nor with
      autologous CD4+ T cells specific for tetanus toxoid. These findings demonstrate
      that tumor Ag can be processed and presented by EBV-transformed B cells to MHC
      class II-restricted tumor-specific CD4+ T cells. They also provide a model system
      for direct identification of these tumor-derived antigens.

PMID- 7516928
TI  - Structure and function of the cyanelle genome.

PMID- 7516929
TI  - Swainsonine, a glycosylation inhibitor, enhances both lymphocyte efficacy and
      tumour susceptibility in LAK and NK cytotoxicity.
AB  - Swainsonine (SW) inhibits the formation of N-linked complex oligosaccharides and
      has previously been shown to inhibit experimental metastasis in nude mice models.
      The present studies with human effector cells have shown that SW enhanced both
      lymphokine activated killer cell (LAK) and natural killer (NK) cytotoxicity in
      standard 51Cr-release assays. SW also increased the susceptibility of human K562
      and Colo 320 target cells to NK and LAK cytotoxicity. The peak response of both
      LAK effectors and targets to SW occurred at 1-2 micrograms/ml SW. A novel finding
      was that SW enhanced the interleukin 2 (IL-2) beta chain receptor subunit
      expression on both LAK and NK cells to a greater extent than its enhancement of
      the IL-2R alpha (CD25 or TAC) receptor expression on LAK effectors. In addition,
      increases in both these receptors occurred at the doses of SW which augmented LAK
      cytotoxicity. We conclude that the anti-metastatic effects of SW have an
      immunological component which is maximal at 1-2 micrograms/ml SW. This suggests
      that dosage may be an important consideration to obtain optimal potential of SW
      in any future human cancer therapy.

PMID- 7516933
TI  - Visual design for the user interface, Part 1: Design fundamentals.
AB  - Digital audiovisual media and computer-based documents will be the dominant forms
      of professional communication in both clinical medicine and the biomedical
      sciences. The design of highly interactive multimedia systems will shortly become
      a major activity for biocommunications professionals. The problems of human
      computer interface design are intimately linked with graphic design for
      multimedia presentations and on-line document systems. This article outlines the
      history of graphic interface design and the theories that have influenced the
      development of today's major graphic user interfaces.

PMID- 7516930
TI  - Interaction of interleukin-1 and interferon-gamma on fibroblast growth factor
      induced angiogenesis.
AB  - The interaction of interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) actions
      on several aspects of angiogenesis in vitro and in vivo was studied. The
      proliferation and migration of human umbilical vein endothelial cells cultured
      with basic fibroblast growth factor (bFGF) were synergistically inhibited by
      cotreatment with IL-1 and IFN-gamma. Endothelial cell adhesion to collagen was
      suppressed by IL-1 and the effect was slightly enhanced by the combination of IL
      1 and IFN-gamma. Local administration of IL-1 (10,000 U) and IFN-gamma (1,000 U)
      inhibited bFGF-induced angiogenesis in the skin of mice, and synergistic
      inhibitory activity of the combination was demonstrated. Expression of FGF
      receptors was strongly downregulated by the combination, whereas expressions of
      epidermal growth factor (EGF) receptors, integrin beta 1 and integrin beta 3 were
      not. EGF partially abrogated the growth-inhibitory effects of IL-1 and IFN-gamma.
      These findings indicate that IL-1 and IFN-gamma are each able to act an
      angiogenesis inhibitor in a situation where FGF plays a major role in
      angiogenesis, and the activity is synergistically enhanced when they are used in
      combination.

PMID- 7516932
TI  - Large nerve cells with long axons in the granular layer and white matter of the
      murine cerebellum.
AB  - The murine cerebellum was investigated by light microscopy using an improved
      modification of Ehrlich's methylene blue supravital staining technique. The dye
      exhibited a special affinity for the perikarya as well as the axons of Purkinje
      cells. In addition, large fusiform or stellate nerve cells which were
      characterised by long descending axons were seen to be distributed diffusely
      within the granular layer and the subcortical white matter. These findings
      indicate the existence of a 2nd type of projection neuron besides the Purkinje
      cells and are therefore in full accordance with older neuroanatomical
      observations based on silver impregnation. When correlated with recent studies on
      the occurrence of different calcium-binding proteins, the results show that the
      large perikarya demonstrated immunohistochemically within the granular layer seem
      to belong to the group of methylene blue positive neurons. Nevertheless, the
      definitive association of a single neuron with a nerve cell class is only
      possible if the axon is stained and clearly identifiable. Because of its
      selectivity for a special type of nerve cell, including its axon, the
      histological method used in this study may therefore also be suitable for
      investigating other parts of the brain and the spinal cord.

PMID- 7516934
TI  - Can the biomedical communications unit survive?

PMID- 7516931
TI  - Nitric oxide synthase in neurons of the gastrointestinal tract of an avian
      species, Coturnix coturnix.
AB  - The distribution of reduced nicotinamide adenine dinucleotide phosphate (NADPH)
      diaphorase staining and its colocalisation with nitric oxide synthase
      immunoreactivity was examined in neurons of the quail gastrointestinal tract.
      Immunoreactivity and enzyme activity were found in identical populations of
      neurons. Nitric oxide synthase activity was present in 30-40% of myenteric nerve
      cells in each region. Numerous reactive cells were also in the submucous plexus
      and many positive nerve fibres innervated the muscle. In the small intestine,
      some of the fibres innervating the circular muscle formed a deep muscular plexus
      and in the large intestine there was a submuscular plexus. Nerve fibres formed
      baskets around nerve cells of myenteric and submucous ganglia. Intramural
      arterioles were innervated, most prominently in the oesophagus and stomach. Very
      few fibres innervated the mucosa, except for some oesophageal glands and the core
      of villi in the cloaca. It is concluded that nitric oxide is probably involved in
      transmission to muscle of the avian intestine, as it is in mammals, and that it
      is probably also produced at neuroneuronal and neurovascular junctions.

PMID- 7516936
TI  - Infarct measurement methodology.

PMID- 7516937
TI  - Variability in adaptive behavior in children with developmental delay.
AB  - Although diagnosticians have become increasingly sensitized to the importance of
      assessing adaptive behavior in persons with intellectual delay, few empirical
      data have been available with respect to the relationship between these two
      dimensions of development in referred clinical populations. Subjects in this
      study were 117 children aged 9 to 111 months who had significantly intellectual
      delay. All subjects were administered the Developmental Profile II (DPII), a
      parent-report measure of functional and adaptive skills. Seventy-nine percent of
      the children with mild intellectual delay obtained Self-Help age scores on the
      DPII and 74.2% Social Age scores that were within broad chronological age
      expectations. A surprising percentage of children with moderate and severe
      intellectual delays also obtained adaptive age scores at this level.

PMID- 7516935
TI  - Alterations in tau immunostaining in the rat hippocampus following transient
      cerebral ischemia.
AB  - Previous studies in gerbils have shown that cytoskeletal disruption and a loss of
      the dendritic microtubule-associated protein, MAP2, may occur after short periods
      of transient global ischemia. tau, a predominantly axonal microtubule-associated
      protein, has not been examined following ischemia. We compared neuronal damage
      with alterations in MAP2, tau, and 72-kD heat shock protein (HSP72)
      immunostaining at various reperfusion times following 20 min of ischemia in the
      rat four-vessel occlusion model. tau accumulated in neuronal cell bodies
      throughout the hippocampal formation 30 min to 2 h after the ischemic insult.
      Perikaryal tau immunostaining was transient in most regions, but persisted in
      polymorphic hilar neurons. This was accompanied by a loss of immunostaining in
      the target of many hilar neurons, the inner molecular layer of the dentate gyrus.
      The same neuronal populations that exhibited increased tau immunostaining of
      perikarya later displayed an induction of HSP72 immunoreactivity. In contrast,
      loss of MAP2 immunostaining was not consistently observed before neuronal death
      and did not correspond to HSP72 induction. The altered tau immunostaining is not
      the direct result of excitotoxic insult, as intrahippocampal injection of kainic
      acid did not cause the somal accumulation of tau, but did cause disruption of
      MAP2 immunostaining. Taken together, the results suggest that the somal
      accumulation of tau is an early, sensitive, and selective marker of ischemic
      insult.

PMID- 7516940
TI  - Palliative care nursing education: a review of research findings.
AB  - Recently, there has been considerable interest shown in research studies that
      identify the needs of dying patients and their families, as well as the needs of
      health care professionals who care for the dying. This particular type of
      research has significantly contributed to an increase in the awareness of health
      care professionals of the need to look critically at the ways dying patients and
      their families are cared for. Moreover, this awareness has led to demands for
      death education and, in recent years, advances have been made in identifying a
      body of palliative care knowledge to teach health care professionals. This
      progress has been particularly notable within nursing. This paper presents an
      analysis of some of the key education research undertaken, focusing specifically
      on studies related to death education. Some potential areas for future research
      in palliative nursing education are also discussed.

PMID- 7516938
TI  - Gingival metastasis as first sign of an undifferentiated carcinoma of the lung.
AB  - BACKGROUND: Metastases of internal tumors to the oral cavity are unusual and
      involve in most cases maxilla and mandible. Metastases to the gingival soft
      tissue are extremely rare. OBJECTIVE: To report a case of gingival metastasis
      from undifferentiated carcinoma of the lung. METHODS: The lesion was removed and
      hematoxylin and eosin sections were performed. Immunohistochemical investigations
      were performed with a standard three-step immunoperoxidase technique on formalin
      fixed, paraffin-embedded tissue sections using anti-CEA, anti-S-100, HMB45, and
      anti-LCA antibodies. RESULTS: Based on clinicopathologic findings, a diagnosis of
      metastasis from undifferentiated carcinoma of the lung was established. Further
      investigations revealed a primary undifferentiated carcinoma of the lung.
      CONCLUSION: Metastasis from internal neoplasms should be considered among other
      differential diagnoses in the evaluation of gingival tumors. In the present case,
      onset of oral lesion preceded detection of the primary lung tumor. Complete
      screening of the patient should therefore follow a diagnosis of gingival neoplasm
      of unknown origin.

PMID- 7516939
TI  - Components of preoperative patient teaching in Kuwait.
AB  - Even before the invasion of Kuwait by the Iraqis in August 1990, the Ministry of
      Health (MOH) hospitals were overcrowded with patients. This overcrowding was very
      obvious on surgical floors. Two major reasons for the overcrowding were the high
      rate of admissions and the overstaying of some patients. The main reasons for
      overstaying were postoperative complications and patients' anxiety regarding
      their wounds, both of which could have been prevented or minimized through
      preoperative patient teaching. This study was done in order to identify the major
      components of a preoperative patient teaching programme as viewed by Arab and non
      Arab surgical nurses and patients, which will serve as a guide in formulating a
      structured teaching programme for surgical patients. It will also assess the
      adequacy of preoperative patient teaching done by nurses.

PMID- 7516942
TI  - A case report. Underdiagnosis of an odontogenic keratocyst: common cyst can be
      controversial lesion.
AB  - A mass removed from a 68-year-old patient was misdiagnosed as a benign squamous
      epithelial cyst. The lesion actually represented an odontogenic keratocyst. The
      patient had no sign of the basal cell nevus syndrome. After 12 months, there has
      been no recurrence.

PMID- 7516941
TI  - Changes in immunoglobulin, complement and acute phase protein levels in the
      depressed patients and normal controls.
AB  - Recently, several authors have reported that immunoglobulin IgM, complement C3c,
      complement C4, and positive acute phase proteins (e.g., haptoglobin, alpha 1-acid
      glycoprotein and alpha 1-antitrypsin) were significantly increased, while
      negative acute phase proteins (e.g., albumin and transferrin), were decreased in
      depressed patients. In the present study, the levels of the immunoglobulin IgM,
      complement C3c, C4, alpha 1-antitrypsin and haptoglobin were found to be
      significantly increased in 20 unipolar depressed patients compared to healthy
      controls. The concentrations of total protein and albumin were significantly
      reduced in these patients. The concentrations of alpha 1-protein, (which is
      related to alpha 1-antitrypsin), and alpha 2-protein (which related to
      haptoglobin), were also significantly elevated in unipolar depressed patients.
      The results suggest that unipolar depression is associated with an acute phase
      response, which is possibly caused by changes in cytokines and corticosteroid
      secretion in depressed patients.

PMID- 7516943
TI  - The sympathetic efferent innervation of the cutaneous and muscle veins in cats. A
      comparative study using retrograde localization with horseradish peroxidase.
AB  - Previous studies using electrical stimulation, tension recording and fluorescence
      histochemical methods indicate that variations in the sympathoadrenergic
      innervation exist in regional veins of the limb. In the present experiment, we
      used horseradish peroxidase (HRP) as a retrograde tracer to localize and
      quantitate the sympathetic innervations to the saphenous, femoral and muscle
      veins in the cat. The animal was anesthetized with pentobarbital. In three groups
      of cats, a segment of saphenous (n = 8), femoral (n = 8) and muscle (n = 10) vein
      was isolated. HRP was applied on the outer vein wall for 3-4 h to allow uptake
      into the nerve endings. The paravertebral sympathetic chain on the same side of
      HRP application was dissected after the animal was killed and fixed 60 h
      following the application of tracer. HRP-labeled neurons were counted in each
      sympathetic ganglion from L1 to S1. The average number of neurons (mean +/- SE)
      were 913 +/- 99, 732 +/- 70 and 234 +/- 32, respectively, for saphenous, femoral
      and muscle vein. There was no statistical difference between the saphenous and
      femoral vein (P > 0.1). The muscle vein was far less innervated (P < 0.001). When
      the surface area (mm2) of the vein segment for HRP application was taken into
      account, the neurons per mm2 were 44.1 +/- 4.8 for saphenous vein, 24.6 +/- 1.8
      for femoral vein and 10.2 +/- 1.3 for muscle vein. The neuron density was
      significantly different among the three groups (P < 0.01). In a single ganglion,
      the distribution of HRP-neurons appeared to be scattering in pattern.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7516944
TI  - The distribution and colocalization of neuropeptides in fish cardiac neurons.
AB  - Most if not all intracardiac nerve cell bodies in four species of teleost fish
      and a primitive air breathing fish contained immunoreactivity (IR) to vasoactive
      intestinal peptide (VIP). Intracardiac nerve cell bodies contained no other
      neuropeptide although galanin (GAL)-, substance P (SP)- and calcitonin gene
      related peptide (CGRP)-IR were detected in cardiac axons. Varicose VIP-IR axons
      were observed in close association to the cardiac muscle in the sinus venosus and
      atrium, but not in the ventricle. Slightly less than half the total number of VIP
      IR axons also contained colocalised GAL-IR. A smaller number of varicose axons
      containing colocalised SP- and CGRP-IR were also present in the sinus venous and
      atrium. In addition, a subpopulation of CGRP-IR axons present in the sinus
      venosus and atrium did not contain SP-IR. SP-IR axons lacking CGRP-IR formed
      boutons around the axon hillock and soma of the majority of VIP-IR nerve cell
      bodies. Associated with a small number of VIP/-ganglion cells were VIP/- boutons.
      No neuropeptides were observed in the ventricle of any species of fish studied
      here. These results suggest that a VIP-like peptide is localised in the
      cholinergic postganglionic parasympathetic neurons. Associated with some of these
      neurons are nerve boutons containing either SP alone or VIP alone. In addition,
      the fish heart is innervated by extrinsic nerve fibres containing: GAL/VIP; CGRP
      alone; and CGRP/SP.

PMID- 7516945
TI  - Dynorphin B is present in sensory and parasympathetic nerves innervating pial
      arteries.
AB  - Dynorphin B (dyn B) in trigeminal ganglion cells and in perivascular nerve fibers
      in pial arteries was demonstrated in rat, guinea-pig, and monkey by
      immunohistochemistry. The pathway from the trigeminal ganglion, which runs via
      the nasociliary nerve and ethmoidal foramen to the pial arteries, was shown in
      rat by retrograde tracer technique and nerve section. In the guinea-pig the
      peptide was demonstrated to coexist with substance P and calcitonin gene-related
      peptide in neurons of the trigeminal ganglion and pial nerve fibers, i.e., it was
      present in cerebrovascular sensory nerves with primarily nociceptive function.
      Another finding in guinea-pig was a coexistence of dyn B with vasoactive
      intestinal polypeptide in the pial nerve fibers and neurons of the sphenopalatine
      ganglion, indicating a presence also in parasympathetic nerves to the cerebral
      vessels. No vasomotor effect of dyn B could be detected in isolated segments of
      rat pial arteries, which rules out a direct postsynaptic effect on vascular tone.
      The peptide did not display a prejunctional modulatory action on the adrenergic
      nerves present in the vessels. The function of dyn B in the cerebrovascular
      nerves is discussed.

PMID- 7516946
TI  - Bulbospinal neuropeptide Y-immunoreactive neurons in the rat: comparison with
      adrenaline-synthesising neurons.
AB  - Immunohistochemistry and retrograde tracing using cholera toxin B subunit
      colloidal gold (CTB-gold) has been used to identify neurons in the medulla that
      contain neuropeptide Y and project to the area of the intermediolateral cell
      column in either the upper (T2-T4) or the lower (T8-T9) thoracic spinal cord. The
      rostrocaudal distributions of neuropeptide Y neurons and neuropeptide Y/CTB-gold
      neurons have been compared with the distributions of adrenaline-synthesising,
      phenylethanolamine N-methyltransferase-containing neurons and phenylethanolamine
      N-methyltransferase/CTB-gold neurons visualised in adjacent sections. In
      particular areas of the rostral medulla similarities in the numbers and
      distributions of neuropeptide Y neurons and phenylethanolamine N
      methyltransferase neurons suggested a coexistence of the peptide within the
      catecholamine neurons. However, at the most rostral levels of the rostral ventral
      medulla, the large numbers of phenylethanolamine N-methyltransferase neurons were
      not matched by similar numbers of neuropeptide Y neurons, so that the
      phenylethanolamine N-methyltransferase neurons in this area could not all contain
      neuropeptide Y. In the rostral ventral medulla fewer neuropeptide Y/CTB-gold
      neurons than phenylethanolamine N-methyltransferase/CTB-gold neurons were
      observed, so that these bulbospinal peptide neurons might define a subset of the
      phenylethanolamine N-methyltransferase/CTB-gold neurons, accounting for 25% of
      the total phenylethanolamine N-methyltransferase bulbospinal projection from the
      rostral ventral medulla. Other neuropeptide Y/CTB-gold neurons in the dorsal
      medulla are also likely to contain phenylethanolamine N-methyltransferase.
      Finally, a population of neuropeptide Y/CTB-gold neurons was identified in the
      caudal ventral medulla, these neurons appear not to contain catecholamine
      synthesising enzymes.

PMID- 7516948
TI  - Induction of autoimmune phenomena in patients with chronic hepatitis B treated
      with gamma-interferon.
AB  - All interferons display antiviral properties, but gamma-interferon especially has
      an immunomodulatory effect and may induce autoimmune phenomena. Therefore the
      formation of autoantibodies was investigated in patients with chronic hepatitis B
      treated with gamma-interferon. Eleven patients (all HBs-Ag and HBe-Ag positive)
      were treated for 6 months with recombinant gamma-interferon. The following
      antibodies were tested: anti-nuclear antibodies, smooth muscle antibodies, anti
      actin, anti-mitochondrial antibodies of subgroup anti-M2 and anti-M9 as well as
      naturally occurring antibodies, antibodies to liver-kidney microsomes, vascular
      endothelial cell antibodies, sarcolemmal antibodies, parietal cell antibodies,
      thyroglobulin antibodies and antibodies to laminin and keratin. All patients
      produced autoantibodies during therapy. The maximum antibody formation and the
      highest titres were observed in the period between the 3rd and 6th month after
      therapy began. The cumulative frequencies of the different antibody specificities
      were as follows: n = 6 anti-nuclear antibodies, n = 7 smooth muscle antibodies, n
      = 1 anti-actin, n = 12 antibodies to laminin or keratin, n = 6 endothelial cell
      antibodies/sarcolemmal antibodies, n = 6 anti-mitochondrial antibodies, n = 1
      antibodies to liver-kidney microsomes, n = 2 thyroglobulin antibodies, n = 4
      parietal cell antibodies. Antibodies persisted in six patients over a period of 3
      months (two cases of parietal cell antibodies and one case of antibodies to liver
      kidney microsomes) and were still detectable in three patients 6 months after
      therapy. In three patients new antibody formation occurred 1 month after therapy.
      So far, clinical signs of an autoimmune disorder have not appeared in any of the
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516947
TI  - Production of age-synchronous mass cultures of Caenorhabditis elegans.
AB  - Methods are described for culturing large populations of age-synchronous
      Caenorhabditis elegans throughout the adult life span. Contamination of adult
      populations by progeny was prevented by constructing double-mutant strains that
      produce progeny at a frequency of less than .005 per adult at the nonpermissive
      temperature (25.5 degrees C). Of four double-mutant strains that we have
      characterized, three have wild-type life spans at 25.5 degrees. The other strain
      contains a mutant allele, age-1(hx542), that results in an increase in life span
      of 60% over wild type. All four strains produced sufficient numbers of progeny at
      the permissive temperature (20 degrees C) to generate populations containing 1-5
      x 10(6) nematodes within two weeks. Age-synchronous young adult populations were
      produced using these strains and have been maintained as adults both in liquid
      culture and on agar medium. Procedures that reduce E. coli contamination by 30
      fold in harvested samples of adults are also described.

PMID- 7516950
TI  - THF gamma 2 stimulates cytokine release by peripheral blood mononuclear cells of
      patients with chronic hepatitis B virus infection.
AB  - A recent study indicated that thymic hormones have antiviral effects in human
      hepatitis B virus infection and woodchuck hepatitis virus infection. These
      hormones are known to exert immunomodulatory effects on lymphocyte maturation and
      function; because these are abnormal in patients with chronic hepatitis B virus
      infection, we have examined the effects of a thymic hormone (THF gamma 2) on
      peripheral blood mononuclear cells from patients with chronic hepatitis B virus
      infection. THF gamma 2 (50 or 150 ng/ml) alone was without effect; in the
      presence of low doses of the mitogen phytohaemagglutinin, it had a broad effect
      in patients and controls. The effect on interleukin-2 production was greater in
      patients than controls with a significant increase in production at 150 ng/ml for
      patients alone (p = 0.037). Tumour necrosis factor alpha production was enhanced
      in all patients and controls, with a greater effect seen at 150 ng/ml THF gamma 2
      than 50 ng/ml. There was no effect on interferon gamma production or on the
      expression of membrane markers of T-cell activation. THF gamma 2 has substantial
      immunomodulatory activity in chronic hepatitis B virus carriers and in vivo
      assessment of THF gamma 2 in chronic hepatitis B virus is indicated.

PMID- 7516953
TI  - Long-term effect of interferon therapy in chronic hepatitis B.

PMID- 7516954
TI  - Preface: policy issues related to clinical practice guidelines.

PMID- 7516952
TI  - Hepatitis C virus replication and antibodies to structural and nonstructural
      viral proteins in chronic hepatitis C.
AB  - The correlation between hepatitis C virus replication and antibodies to both
      structural (core) and nonstructural (C100-3) hepatitis C virus proteins (anti
      HCVcore and anti-C100-3, respectively) was assessed. The concentration of serum
      hepatitis C virus RNA was determined by a competitive reverse transcription
      polymerase chain reaction assay, and antibody titers were determined by endpoint
      dilution. No correlation was found between viremic levels and antibody titers in
      42 chronic hepatitis C patients. At the end of a 6-month course of interferon
      alpha therapy, 18 patients became negative for hepatitis C virus RNA. In the
      other 24 patients, post-treatment viremic levels ranged from 10(-6.5)-10(0.5) of
      pretreatment levels. Both anti-C100-3 and anti-HCVcore frequently decreased in
      patients whose viremic levels dropped to the negative range or to < 10(-2) of
      pretreatment levels. Anti-C100-3 decreased in all such cases (25/25), while anti
      HCVcore decreased in 18/25 (72%) (p < 0.01), indicating that anti-C100-3 is more
      likely to decrease following suppression of viral replication than anti-HCVcore.
      These data suggest that hepatitis C virus antibodies may serve as a marker of
      suppression of viremia following interferon therapy even in patients who do not
      clear the virus.

PMID- 7516951
TI  - Interferon antibodies in patients with chronic hepatitic C virus infection
      treated with recombinant interferon alpha-2 alpha.
AB  - Patients treated with alpha-2a interferon for chronic hepatitis C may produce
      anti-interferon antibodies whose effect, if any, on the individual response to
      therapy has not been fully clarified. The prevalence and kinetics of anti
      interferon, including those of neutralizing type, have been studied in 60
      patients with chronic hepatitis C enrolled in a randomized controlled trial of
      recombinant alpha-2a interferon. Thirty patients received interferon while 30
      were untreated controls. Two different methods, an enzyme immunoassay and an
      antiviral neutralization bioassay, were used and serial serum samples from each
      patient were analyzed. Enzyme immunoassay-positive anti-interferon appeared in
      60.7% of treated patients within 6 months of therapy; antiviral neutralization
      bioassay-positive anti-interferon appeared in 52.9% of these enzyme immunoassay
      positive patients, and was associated with high enzyme immunoassay reactivity and
      long-term persistence. Anti-interferon was detected in 75% of patients showing no
      response to interferon. Antibodies were also detected in three out of six
      patients who showed alanine aminotransferase normalization persisting up to the
      end of treatment and in 8 out of 14 patients who showed an initial marked
      reduction or even normalization of alanine aminotransferase, followed by
      reactivation of liver damage during treatment. Interestingly, patients who became
      anti-interferon positive before complete alanine aminotransferase normalization
      later showed reactivation of liver damage independently of interferon dose
      reduction, while patients who became positive for anti-interferon after complete
      alanine aminotransferase normalization either did not reactivate or did so only
      after interferon dose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516955
TI  - Liability issues in the management of pain.
AB  - Liability issues associated with pain management are important to health-care
      providers, patients, pharmaceutical companies, manufacturers of pain-management
      devices, health-care payors, and society at large. This article discusses five
      specific legal liability concerns: (a) health-care providers' liability to
      patients and/or exposure to professional discipline for inappropriate pain
      management, (b) health-care providers' liability to third parties for injury
      caused by patients treated for pain, (c) the legal distinction between pain
      management and euthanasia or physician-assisted suicide, (d) health-care payors'
      liability to patients for cost-containment decisions that impact on pain
      management, and (e) manufacturers' and health-care providers' liability for the
      risks and side effects of prescription drugs and pain-management devices.

PMID- 7516949
TI  - PreS1 deleted variants of hepatitis B virus in patients with chronic hepatitis.
AB  - Defective hepatitis B virus lacking 183 bases of the 3'-terminus part of the
      preS1 region was found in the sera of two patients with chronic hepatitis B virus
      infection. Results of sequencing analysis of samples with or without polymerase
      chain reaction yielded the same result, proving that this deletion was not due to
      an artifact obtained during polymerase chain reaction. One of the deletion ends
      lay in TCAGG that appeared five times in the genome of subtype adr and the other
      end was identified as TCAGG in direct repeats of the genome. The mutated
      hepatitis B virus became predominant in one patient's serum only after
      consecutive interferon therapy, suggesting that the deleted part might play a
      role in viral elimination from the circulation.

PMID- 7516956
TI  - Ethics and pain management: respecting patient wishes.
AB  - The fear of pain is common among cancer patients. The management of cancer pain
      can raise troubling ethical issues for medicine and society. Medical caregivers
      have an ethical duty to provide therapy that benefits patients by achieving one
      or more goals of medicine at all points. Pain and symptom relief may be the only
      achievable goal when curative therapy has failed. Relief of pain can restore
      decision-making capacity and enhance the patient's right to self-determination.
      The underpinning ethical principles and extensions of these principles in the
      medical context of pain control with varying medical goals in cancer care,
      including dying patients, is explored.

PMID- 7516958
TI  - Effects of pain duration on psychosocial adjustment in orthopedic patients: the
      importance of early diagnosis and treatment of pain.
AB  - Six hundred thirty-five orthopedic patients who were consecutively referred to an
      outpatient pain assessment service were grouped into one of five pain-duration
      categories: 0-3 mo, 4-6 mo, 7-9 mo, 9-12 mo, and more than 12 mo. Comprehensive
      psychosocial assessment of the patients revealed that longer pain-duration
      patients are older, complain of greater body surface in pain, have had more
      surgery, have been out of work longer, report taking more pain medication, have
      been married more times, are more likely to be involved in worker's compensation,
      and report a greater likelihood of current suicidal ideation. In addition,
      patients with longer pain duration showed higher pain intensity and sensitivity,
      less confidence in coping ability, higher dependency traits, and greater
      reliability of self-report. Finally, longer pain duration was associated with
      reports of more symptoms of psychopathologic disturbance, especially in patients
      with pain durations from 9 to 12 mo. Because the data presented are correlation
      in nature, prospective analysis of the psychosocial adjustment of orthopedic pain
      patients is suggested.

PMID- 7516959
TI  - Probable cervical midline epidural septum complicating the treatment of a patient
      with upper extremity sympathetically maintained pain.
AB  - We present a woman who developed left arm sympathetically maintained pain (SMP,
      or "shoulder-hand syndrome") as a result of brachial plexus injury. After
      confirmatory diagnosis with both stellate local anesthetic block and intravenous
      phentolamine infusion, the patient had a cervical epidural catheter placed and a
      local anesthetic infusion started. After numerous unilateral blocks were
      obtained, a cervical epidurogram demonstrated a probable cervical midline
      epidural septum. Catheter placement was adjusted, and a successful chemical
      sympathectomy was performed for 6 days. This resulted in significant relief of
      the patient's shoulder pain as well as almost complete resolution of the
      patient's left arm SMP symptoms. This case represents, to our knowledge, the
      first documentation of the use of phentolamine for the diagnosis of SMP secondary
      to pathology at a site proximal to that of symptomatology, as well as the first
      documentation of presumptive cervical midline epidural septum.

PMID- 7516957
TI  - The ethics of pain management for cancer patients: case studies and analysis.
AB  - Numerous national guidelines have addressed the ethical issues of pain
      management. Despite these efforts, many cancer patients get inadequate pain
      control. While there are many reasons for this situation, part of the problem is
      the complexity of applying these ethical standards to particular cases. In an
      effort to strengthen such clinical judgment, this essay analyzes two cases of
      pain management for cancer patients.

PMID- 7516960
TI  - Definition of a nonlinear conformational epitope for the apolipoprotein B-100
      specific monoclonal antibody, MB47.
AB  - The apolipoprotein (apo) B-100-specific monoclonal antibody MB47 has been widely
      used in lipoprotein metabolism and atherosclerosis research. When bound to apoB
      100 on low density lipoproteins (LDL), antibody MB47 completely blocks the
      binding of LDL to the LDL receptor. The epitope for antibody MB47 has previously
      been mapped to the vicinity of apoB-100 amino acid (aa) residue 3500. To map the
      epitope for antibody MB47 more precisely, we used recombinant bacterial fusion
      proteins. Antibody MB47 bound strongly to a fusion protein containing apoB-100 aa
      3214-3728, but no specific binding was observed to fusion proteins containing aa
      3214-3351, 3214-3506, 3351-3506, or a fusion protein containing aa 3214-3351 and
      3506-3728. Although antibody MB47 did not bind to aa 3214-3506, it did bind to aa
      3214-3510. Further fusion protein studies revealed that antibody MB47 bound to aa
      3429-3510, but bound only very weakly to aa 3453-3510, indicating that aa 3429
      3453 constitute an important part of the MB47 epitope. Subsequent fusion protein
      studies revealed that MB47 bound much more strongly to aa 3429-3523, 3429-3544,
      3429-3565, and 3429-3590 than to aa 3429-3510. Thus, aa 3507-3523 also constitute
      an important part of the MB47 epitope. In summary, the fusion protein data
      indicated that two nonlinear domains of apoB-100 separated by approximately 53 aa
      (the 25 residues from aa 3429 to 3453 and the 17 residues from aa 3507 to 3523)
      form key parts of the MB47 epitope.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516961
TI  - The molecular basis for epitopes on the free beta-subunit of human chorionic
      gonadotrophin (hCG), its carboxyl-terminal peptide and the hCG beta-core
      fragment.
AB  - The molecular basis for antigenic determinants on the free beta-subunit of human
      chorionic gonadotrophin (hCG beta), its carboxyl-terminal peptide (hCG beta CTP)
      and the hCG beta-core fragment (hCG beta cf) was elucidated by means of
      monoclonal antibodies (MCAs). The objective of the present study was to resolve
      the antigenic topography of these three molecules in terms of epitope
      identification at different levels of structural organization as well as analysis
      of their spatial arrangement. An hCG beta cf preparation, a synthetic peptide
      corresponding to the hCG beta CTP (beta 109-145), overlapping synthetic peptides
      spanning the entire amino acid sequence of hCG beta, and a reduced and alkylated
      hCG beta preparation were assayed in a solid-phase one-site enzyme-linked
      immunoassay and in a soluble-phase direct-binding radioimmunoassay (RIA) or
      competitive RIA. The antigenic topography was mapped by incorporating the MCAs
      into two-site binding assays. On the surface of free hCG beta, nine different
      epitopes (beta 1-beta 9), arranged in three spatially distinct domains, could be
      distinguished. Epitopes beta 1-beta 7 were located in a single large domain on
      both hCG beta and the hCG beta cf whereas hCG beta CTP contained two
      topographically distant determinants, designated beta 8 and beta 9 respectively.
      All but the two epitopes located on hCG beta CTP (beta 8 and beta 9) were
      destroyed by reducing and alkylating hCG beta, suggesting that most antigenic
      determinants are predominantly non-contiguous and require an intact tertiary
      structure whereas the molecular structure of hCG beta CTP is linear. At a
      molecular level, amino acid residues spanning hCG beta 45-52, hCG beta 137-144
      and hCG beta 113-116 contributed to the formation of epitopes beta 5, beta 8 and
      beta 9 respectively. We have also shown that the hCG beta cf represents the
      immunodominant part of the free beta-subunit of hCG, containing seven mainly
      conformationally determined epitopes, one of which has a share of the sequence
      beta 45-52. The hCG beta CTP does not play a critical role in the immunologically
      important tertiary structure of hCG beta and was itself found to be a
      predominantly continuous sequence also within the native hormone, expressing two
      spatially distant antigenic determinants located within residues beta 113-116 and
      beta 137-144 respectively.

PMID- 7516963
TI  - Control of Aedes albopictus larvae using time-release larvicide formulations in
      Louisiana.
AB  - The ability of time-release formulations of larvicides and insect growth
      regulators (IGRs) to provide long-term control of Aedes albopictus was
      investigated in the field. Larvicides used in the study were Bactimos pellets
      (Bacillus thuringiensis var. israelensis, active ingredient) and Abate pellets
      (temephos, active ingredient). The IGR Altosid (methoprene, active ingredient)
      was used in pellet and sand formulations. Application rates were higher than
      label recommendations. In a preliminary test, clay flower bowls were treated with
      2 g of material. Bactimos pellets failed to provide control after 60 days. Abate
      pellets and the Altosid formulations provided essentially 100% control for 150
      days. After 360 days in the field, the Abate pellets produced 100% larval
      mortality, and significant levels of control were provided by the Altosid
      formulations and the Bactimos pellets. In a small-scale operational trial of this
      technique, 1 g of Altosid pellets was applied to every container that could be
      located in 2 urban residential neighborhoods in Lake Charles, LA. Aedes
      albopictus biting populations were monitored weekly in the treated areas and in
      an untreated control area. Biting population densities declined significantly in
      treated areas compared with the control area. Results suggested that long-term
      control of Ae. albopictus populations can be achieved economically with one
      application of Altosid pellets or Abate pellets in containers.

PMID- 7516962
TI  - Response of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) and
      IGFBP-3 to IGF-I treatment in severe insulin resistance.
AB  - It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential
      therapeutic agent in diabetes mellitus. It is known to have glucose-lowering
      effects in normal individuals, in patients with non-insulin-dependent diabetes
      (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs)
      have the potential to affect the biological activity of rhIGF-I. We have studied
      the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with
      Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20
      mg rhIGF-I, glucose concentrations fell from 44.1 +/- 7.2 to 31.5 +/- 7.2
      (S.E.M.) mmol/l (P = 0.001), and insulin and C-peptide levels fell from 920 +/-
      62 to 542 +/- 45 mU/l (P = 0.008) and 5466 +/- 633 to 3071 +/- 297 pmol/l (P =
      0.02) respectively. Significant lowering of phosphate, magnesium and alkaline
      phosphatase concentrations was also noted. IGF-I levels rose from 48 +/- 10.2 to
      410 +/- 50.1 micrograms/l (P = 0.001), and those of IGF-II fell from 279.8 +/-
      8.3 to 104.3 +/- 7.9 micrograms/l (P = 0.001). IGFBP-1 concentrations did not
      significantly change during the infusion but those of IGFBP-3 increased from 1655
      +/- 127 to 2197 +/- 334 micrograms/l (P = 0.002), despite a significant fall in
      GH concentrations from 10.7 +/- 2.6 to 4.1 +/- 1.1 mU/l (P = 0.007), suggesting
      that IGFBP-3 regulation is also IGF-I-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7516964
TI  - Tolerance of the planarian Dugesia tigrina (Tricladida: Turbellaria) to
      pesticides and insect growth regulators in a small-scale field study.
AB  - Two insect growth regulators, methoprene and a benzyl-1,3,benzodioxole (J-2931),
      had no detrimental effects on Dugesia tigrina under field conditions. Three other
      compounds, resmethrin, temephos, and cyromazine, had only minimal effects.
      Asexual multiplication among these planarian predators exceeded 68% when combined
      with Culex quinquefasciatus larvae and methoprene at different concentration
      levels. Also, this combined treatment with D. tigrina and methoprene resulted in
      high level (98.9%) reduction of Cx. quinquefasciatus populations through the 7-wk
      field study.

PMID- 7516966
TI  - Effect of granulocyte colony-stimulating factor on neutropenia in liver
      transplant recipients with hypersplenism.
AB  - The authors present details of their initial experience with use of recombinant
      human granulocyte colony-stimulating factor (rhG-CSF) for preventing neutropenia
      caused by hypersplenism, and, possibly, for reducing the risk of postoperative
      infections in pediatric liver transplant recipients. Seven patients with end
      stage liver disease, three of whom had severe hypersplenism, underwent living
      related liver transplantation (LRLT). The rhG-CSF was administered to the latter
      three patients. Peripheral neutrophil counts decreased immediately after
      reperfusion (to 1500 +/- 300/microL) in the three patients, and returned to
      normal with use of rhG-CSF 3 to 10 days after transplantation. The dosage was
      adjusted to maintain peripheral leukocyte and granulocyte counts above
      5,000/microL and 2,000/microL, respectively. This initial clinical trial showed
      that rhG-CSF administration restores the leukocyte counts of patients who have
      hypersplenism, without any significant adverse effects, and that rhG-CSF holds
      promise for reducing the risk of infections after liver transplantation.

PMID- 7516968
TI  - Misoprostol stimulates leukocyte cyclic adenosine 3',5' monophosphate production
      and synergizes with colchicine: novel combination of established drugs may boost
      anti-inflammatory potential.
AB  - Elevation of intracellular cyclic adenosine 3',5' monophosphate (cAMP) inhibits
      various proinflammatory and immune responses of leukocytes. Among agents known to
      stimulate cAMP production in these cells, prostaglandins E (PGEs) have received
      particular attention as potential immunosuppressive and/or anti-inflammatory
      drugs. Their clinical use, however, is limited by poor oral absorption and
      extreme metabolic instability. Misoprostol, a synthetic analog of PGE1 that can
      be given orally and that has a significantly longer biological half-life, is now
      used to prevent or treat nonsteroidal anti-inflammatory drug (NSAID)-induced
      gastric injury. Because it might also exert anti-inflammatory effects on
      leukocytes, we have characterized the effects of misoprostol on cAMP production
      in these cells. We have found that misoprostol does stimulate cAMP production,
      although with some-what less potency and maximal effect than PGE1; this
      stimulation is synergistically increased by pretreatment of cells with
      colchicine; a clinically relevant dose of colchicine is effective given
      sufficient pretreatment time, and preexposure of cells to colchicine enables a
      clinically relevant dose of misoprostol to stimulate cAMP generation. We conclude
      that colchicine and misoprostol represent a drug combination that might prove
      clinically useful for therapy of inflammatory disease.

PMID- 7516969
TI  - Characterization of cholecystokininA receptor agonist activity by a family of
      cholecystokininB receptor antagonists.
AB  - The dipeptoid cholecystokinin (CCK)B antagonists PD136450, Cam-1279 and CI988
      stimulated amylase release from isolated rat pancreatic acini with an efficacy
      similar to CCK8, but with a much weaker potency (ED50, 0.6, 0.9 and 1.3 microM,
      respectively). In contrast to CCK8, however, none of these compounds elicited
      inhibition of amylase release at supramaximal concentrations. In addition, 10(-4)
      M PD136450 blocked the inhibition induced by high concentrations of CCK8.
      Competitive inhibition of [125I]BH-CCK8 binding by PD136450 indicated that this
      compound bound with a single affinity state to all CCK receptors on acini.
      Maximal stimulation of amylase release by PD136450 was dependent upon occupation
      of virtually the entire complement of CCK receptors. PD136450 at all
      concentrations examined had only a limited ability to stimulate total
      phosphoinositide hydrolysis and at maximum induced only 20% of maximal CCK
      stimulation. Measurement of intracellular calcium ([Ca++]i) by digital imaging of
      Fura-2 indicated that 1 microM PD136450 induced repetitive [Ca++]i oscillations
      with a magnitude of 346.0 +/- 4.5 nM and frequency of 1.3 cycles per min. These
      oscillations were still present in Ca(++)-free medium and were blocked by the
      phospholipase C inhibitor, U73122. Because the dipeptoid compounds can occupy all
      available pancreatic CCKA receptors, these compounds must induce a configuration
      of the receptor different from either CCK8 or the previously characterized
      partial agonist CCK-JMV-180, thereby inducing a distinct signaling pattern.
      Because the dipeptoid compounds do not fully mimic CCK actions, it is likely that
      they interact with only some of the critical binding sites within the CCKA
      receptor normally occupied by CCK8.

PMID- 7516967
TI  - L-citrulline reverses the inhibition of nonadrenergic, noncholinergic relaxations
      produced by nitric oxide synthase inhibitors in guinea pig trachea and human
      bronchus.
AB  - Nonadrenergic, noncholinergic relaxations were elicited by field stimulation (8
      Hz, 1 msec, 12 V for 15 sec) of guinea pig trachea desensitized with capsaicin (1
      microM), pretreated with atropine (1 microM), propranolol (1 microM),
      indomethacin (3 microM) and alpha-chymotrypsin (2 U/ml) and contracted with 3
      microM histamine. These relaxations averaged 60 to 80% of the contractions to
      histamine. The relaxations were inhibited markedly by the addition of the nitric
      oxide (NO) synthase inhibitor L-nitro-n-arginine (L-NNA)(30 microM), suggesting
      that these relaxations are due to the release of NO. The inhibition produced by L
      NNA was reversed by either L-arginine or L-citrulline. L-Citrulline was both more
      potent and efficacious than L-arginine in this regard. The ability of L
      citrulline to reverse the inhibition produced by L-NNA was not altered by L
      glutamine (1 mM). The addition of L-citrulline (1 mM) added before L-NNA was
      without effect on the relaxant responses to field stimulation but was able to
      prevent the inhibition produced by L-NNA. L-Citrulline also reversed the
      inhibition produced by another NO synthase inhibitor, L-nitro monomethyl
      arginine. Relaxations to field stimulation (16 Hz, 1 msec, 12 V for 15 sec) of
      human bronchus also were inhibited by 30 microM L-NNA and, as in the guinea pig,
      this inhibition by L-NNA could be reversed by L-citrulline. These results suggest
      that L-citrulline is able to overcome the inhibition of NO synthase by NO
      synthase inhibitors in the guinea pig trachea and human bronchus.

PMID- 7516970
TI  - Involvement of dopamine and excitatory amino acid transmission in novelty-induced
      motor activity.
AB  - The increase in locomotor activity expressed by rats in a novel environment
      demonstrates individual variability, and the present study evaluated an
      hypothesis that the variability resides, in part, in differences in
      neurotransmission in the nucleus accumbens, ventral tegmental area or ventral
      pallidum. Rats were divided into equal groups expressing either a high or low
      response in a novel open field. Subsequently, dopamine, the excitatory amino acid
      agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or the mu
      opioid agonist [D-Ala2, MePhe4, Gly-ol5] enkephalin (DAMGO) was microinjected
      into one of the three brain nuclei, and motor activity was monitored. All three
      drugs produced a dose-dependent elevation in motor activity in all three brain
      nuclei. However, the motor response elicited by dopamine in the ventral pallidum
      and nucleus accumbens was significantly greater in the rats demonstrating a high
      locomotor response to novelty. Similarly, the motor response elicited by AMPA in
      the ventral pallidum, nucleus accumbens or ventral tegmental area was enhanced in
      the high versus low responding rats. In contrast, at no dose and in no brain
      nucleus was the motor response to DAMGO different between high and low responding
      rats. These data indicate that alterations in dopamine and excitatory amino acid
      but not enkephalin neurotransmission in the ventral pallidum, nucleus accumbens
      and ventral tegmental area are associated with differences in motor activity
      expressed by animals in a novel environment.

PMID- 7516971
TI  - Effects of activin A on ionic channels in human FSH-secreting tumour cells.
AB  - 1. Effects of activin A on ionic channels were examined in human FSH-secreting
      tumour cells using electrophysiological techniques. 2. Under voltage clamp with
      the conventional whole-cell clamp technique, the voltage-gated Na+ channel, the T
      and L-type Ca2+ channels, the delayed K+ channel and the A-channel were
      observed. 3. With the nystatin-perforated whole-cell clamp technique, the same
      voltage-gated channels were recorded. Activin A (10(-7) M) increased the
      amplitude of the L-type Ca2+ current, whereas it decreased the amplitude of the
      delayed K+ current. 4. Under current clamp with the perforated whole-cell clamp
      technique, more than 80% of the cells exhibited spontaneous action potentials.
      Application of 10(-7) M activin A depolarized the membrane with a conductance
      increase and augmented action potential frequency. The reversal potential of the
      activin A-induced current was -20 to 0 mV. The activin A-induced current was
      abolished in a Na(+)-free extracellular solution, indicating that the membrane
      depolarization caused by activin A was due to the conductance increase to Na+
      ions through non-selective cation channels.

PMID- 7516965
TI  - SPECT quantitation of cobalt-57-bleomycin to predict treatment response and
      outcome of patients with lung cancer.
AB  - Our hypothesis is that the concentration of 57Co-bleomycin (Co-bleo) in lung
      tumors reflects tumor cell kinetics and thus, prognosis. The relationship between
      the tumor concentration of Co-bleo measured in vivo by quantitative SPECT,
      response to chemotherapy and survival was investigated. METHODS: Twenty patients
      with small-cell lung carcinoma (SCLC) and 49 patients with non-small-cell lung
      carcinoma (NSCLC) were studied. The concentration of Co-bleo was measured by
      SPECT in vivo in the tumor. The correlation between Co-bleo concentration in the
      tumor and the fraction of Co-bleo bound to DNA was investigated in an EMT6 murine
      tumor model and in samples of eight human tumors. RESULTS: Tumors that did not
      respond to treatment showed a significantly higher Co-bleo concentration 8 hr
      after injection than tumors that responded (5.83% +/- 1.97% ID/cc * 10(-3) versus
      2.55% +/- 1.23% ID/cc * 10(-3), p < 0.001). Values of Co-bleo concentration of
      2.97% ID/cc * 10(-3) for SCLC and 2.72% ID/cc * 10(-3) for NSCLC were found to
      best separate patients into short- and long-term survival groups. In the EMT6
      murine tumor model, a good correlation was found between the concentration of Co
      bleo in the tumor and the fraction of Co-bleo bound to DNA (r = 0.75). In human
      tumor samples, a good correlation was found between DNA-bound Co-bleo measured in
      vitro and the concentration measured in vivo by SPECT (r = 0.85). CONCLUSIONS:
      SPECT-measured Co-bleo concentration predicts the response to treatment and the
      outcome in patients with lung tumor by showing Co-bleo binding to DNA and tumor
      cell kinetics.

PMID- 7516972
TI  - Block by amiloride and its derivatives of mechano-electrical transduction in
      outer hair cells of mouse cochlear cultures.
AB  - 1. The effects of amiloride and amiloride derivatives on mechano-electrical
      transducer currents in outer hair cells of the cultured neonatal mouse cochlea
      were examined under whole-cell voltage clamp. 2. At -84 mV transducer currents
      were reversibly blocked by the extracellular application of the
      pyrazinecarboxamides amiloride, benzamil, dimethylamiloride,
      hexamethyleneiminoamiloride, phenamil and methoxynitroiodobenzamil with half
      blocking concentrations of 53, 5.5, 40, 4.3, 12 and 1.8 microM, respectively.
      Hill coefficients were determined for all but the last of these compounds and
      were 1.7, 1.6, 1.0, 2.2 and 1.6, respectively, suggesting that two drug molecules
      co-operatively block the transducer channel. 3. Both the structure-activity
      sequence for amiloride and its derivatives and the mechanism of the block of the
      transducer channel appear to be different from those reported for the high
      affinity amiloride-sensitive epithelial Na+ channels but similar to those of
      stretch-activated channels in Xenopus oocytes. 4. The block by all
      pyrazinecarboxamides was voltage dependent with positive membrane potentials
      releasing the block. The form of the voltage dependence is consistent with a
      voltage-independent binding of the drug to a site that is accessible at
      hyperpolarized but not at depolarized potentials, suggesting that the transducer
      channel undergoes a voltage-dependent conformational change. The channel was not
      blocked by 1 mM amiloride from the intracellular side at either negative or
      positive membrane potentials. 5. The kinetics of the block were studied using
      force steps or voltage jumps. The results suggest that the drug binding site is
      only accessible when the transducer channel is open (open-channel block) and that
      the channel cannot close when the drug molecules are bound. 6. The time
      dependence and voltage dependence of the block together reveal that the
      transducer channel has at least two open conformational states, the transition
      between which is voltage dependent.

PMID- 7516973
TI  - Regulation of A-currents by cell-cell interactions and neurotrophic factors in
      developing chick parasympathetic neurones.
AB  - 1. The developmental regulation of ion channel expression was studied in
      parasympathetic neurones isolated from the chick ciliary ganglion. Whole-cell
      patch clamp recordings were made from ciliary ganglion neurones that were removed
      from the embryo on the ninth embryonic day (E9) and maintained in dissociated
      cell culture for an additional 4 days. Previous studies have shown that the
      expression of a transient voltage-activated K+ current (IA) is regulated by
      unidentified environmental stimuli during these developmental stages. 2. The
      effect of interactions between neurones and target tissue on the expression of IA
      was tested by co-culturing ciliary ganglion neurones with chick striated muscle
      cells. Neurones from the nerve-muscle co-cultures expressed normal amplitudes of
      IA, but the neurones did not express normal levels of IA when they were plated
      onto lysed muscle fibres. 3. The effect of interactions between ganglionic
      neurones and non-neuronal ganglionic cells was tested by culturing ganglia as
      explants rather than as dissociated cells. Neurones isolated from the explant
      cultures did not express normal levels of IA. Similarly, when dissociated
      ganglionic neurones were co-cultured with fibroblasts isolated from embryonic
      chick skin, they did not express normal amplitudes of IA. 4. Chronic
      depolarization caused by growing ciliary ganglion neurones in the presence of
      elevated K+ concentrations did not allow for the normal expression of IA,
      although it did promote the survival of these neurones in vitro. 5. Addition of
      40 ng ml-1 of recombinant human ciliary neurotrophic factor (CNTF) or basic
      fibroblast growth factor (bFGF) to the cell culture medium had no effect on IA
      expression in developing chick ciliary ganglion neurones. However, 40 ng ml-1 of
      acidic fibroblast growth factor (aFGF) stimulated the expression of IA. All
      trophic factors promoted the growth and survival of ciliary ganglion neurones in
      vitro. 6. Dissociated ciliary ganglion neurones were maintained in a culture
      medium containing an aqueous extract of the whole brain. Neurones developing
      under these conditions expressed normal levels of IA. The stimulatory activity of
      the brain extract was destroyed by heating. 7. The expression of IA in chick
      ciliary ganglion neurones developing in vitro can be regulated by soluble growth
      factors and by interactions with certain other cell types. Similar interactions
      may regulate the expression of IA in ciliary ganglion neurones developing in
      situ.

PMID- 7516974
TI  - Modulation of single hyperpolarization-activated channels (i(f)) by cAMP in the
      rabbit sino-atrial node.
AB  - 1. The hyperpolarization-activated 'pacemaker' current (i(f)) was recorded in
      inside-out patches excised from rabbit sino-atrial (SA) node cell membranes. 2.
      Single-channel activity could be resolved in patches containing only a few
      channels; the voltage dependence of single-channel size and single-channel
      conductance (0.97 pS) were similar to those measured previously in cell-attached
      conditions. 3. Perfusion of the intracellular side of the patch membrane with 10
      microM cAMP facilitated the opening of single i(f) channels on hyperpolarization.
      The cAMP-induced i(f) current activation occurred without modification of the
      single-channel conductance. 4. Modification by cAMP of the probability of channel
      opening was investigated with respect to the latency to first opening during
      hyperpolarization and in patches containing a large number of channels (macro
      patches). First-latency histograms showed that cAMP shifts the probability curve
      of first openings to shorter times, in agreement with a cAMP-induced facilitation
      of channel opening. In macro-patches, measurement of the voltage dependence of
      the open probability by a slow voltage ramp protocol showed that cAMP shifts the
      probability curve to more positive voltages without modifying its shape. 5. In
      cell-free macro-patches the normalized open probability curve in control
      solutions was centred around -121.9 mV, a voltage some 30 mV more negative than
      in cell-attached macro-patches. Negative shifting of the curve after patch
      excision could only partly be explained by the removal of intracellular cAMP, and
      progressed with time during the ramp protocol, suggesting the presence of a run
      down process independent from cAMP.

PMID- 7516975
TI  - Ankylosing spondylitis: clinical course in women and men.
AB  - OBJECTIVE: To compare the clinical course; laboratory and radiological features
      of women and men with ankylosing spondylitis (AS). METHODS: Retrospective review
      of charts of 41 women and 41 men with AS (25 B27+ and 16 B27- in each group)
      individually matched for age at onset and disease duration. RESULTS: No
      differences were observed in the clinical picture in either sex, but the disease
      was less severe in women than in men with lesser duration of uveitis attacks,
      lower leukocyte counts (p < 0.05), lower levels of gamma-globulins (p < 0.05),
      and longer asymptomatic periods. At the end of the study, women had less
      restriction of spinal extension (p = NS), less sequelae of uveitis without
      significant visual loss (p = NS), required fewer hip replacements, had less
      frequency of bamboo spine (p < 0.02), and better functional class (p < 0.0027)
      than men. CONCLUSION: There are no significant clinical or radiographic
      differences between women and men with AS. However, the disease was more severe
      in men and these features may be due to sexual dimorphism.

PMID- 7516976
TI  - Expression and regulation of steroid 5 alpha-reductase 2 in prostate disease.
AB  - The androgen dihydrotestosterone is synthesized by the enzyme steroid 5 alpha
      reductase, and it is required for growth and development of the prostate. We used
      immunohistochemistry to examine the expression of the type 2 isozyme of 5 alpha
      reductase in benign prostatic hyperplasia and prostate cancer. The type 2 isozyme
      is highly expressed within stromal cells in both disease states. No type 2
      isozyme is detectable in a lymph node metastasis. Immunoblotting studies show
      that androgen ablation therapies substantially decrease isozyme expression in the
      epididymis but have a lesser effect on expression in the prostate. Finasteride
      therapy (2 weeks to 3 years) did not abolish expression of the prostatic type 2
      isozyme nor did this drug treatment induce expression of the type 1 isozyme.

PMID- 7516977
TI  - The relevance of preoperative cystometrography in patients with benign prostatic
      hyperplasia: correlating the findings with clinical features and outcome after
      prostatectomy.
AB  - Preoperative water cystometrograms in 437 patients with benign prostatic
      hyperplasia (BPH) were examined in a retrospective study. The cystometrographic
      results were analyzed regarding the preoperative clinical features: patient age,
      presence or absence of urinary incontinence, history of urinary retention and
      rate of residual urine. The prognostic value in improvement in voiding difficulty
      and postoperative urinary incontinence was also analyzed at 1 and 6 months after
      elective prostatectomy. Subjective symptoms of the patients were the primary
      reasons for prostatectomy, the majority of which were performed by a single
      competent resectionist (K. T.) who evaluated the outcome but was blinded to the
      cystometric findings. Of these patients 263 (60.2%) had detrusor instability
      (group 1), while 174 did not (group 2). Vesical denervation supersensitivity to
      bethanechol chloride was noted in 47 of 375 patients (12.5%). The difference in
      clinical features was significant between the 2 groups, with group 1 showing
      older patient age (p < 0.01), and a greater incidence of urinary incontinence (p
      < 0.001) and retention (p < 0.001). The difference between groups 1 and 2 in mean
      bladder capacity (p < 0.01), compliance (p < 0.01) and a greater positive rate of
      vesical denervation supersensitivity (p < 0.001) was also significant. The
      clinical and cystometrographic parameters studied worsened with advancing patient
      age. Although the majority of the patients (94.7%) were relieved of obstructive
      symptoms after transurethral prostatectomy (6 months later), 113 (25.9%) were not
      at 1 month. Compared to 324 patients with early improvement (74.1%), those
      without improvement at 1 month were characterized by older age (p < 0.01),
      greater prevalence of preoperative incontinence (p < 0.05), retention (p < 0.01),
      greater residual rate (p < 0.05), a less compliant bladder (p < 0.01) and a
      higher positive rate of vesical denervation supersensitivity (p < 0.05).
      Cystometrographic findings, however, had no relevance to late (6 months) outcome
      of voiding difficulty. On the other hand, postoperative incontinence was noted in
      100 patients (22.9%) at 1 month after transurethral prostatectomy, with the
      majority having episodes similar to those experienced preoperatively (70.0%) as
      well as detrusor instability (87.0%). They also were older (p < 0.01), and had a
      less compliant bladder (p < 0.01) and a higher positive rate of vesical
      denervation supersensitivity (p < 0.01) than did continent patients. Only 18
      elderly patients (4.1%) remained incontinent 6 months later, all with a less
      compliant (p < 0.01) and more unstable (p < 0.01) bladder initially. The genesis
      of this detrusor dysfunction was believed to be aging in male patients, in whom
      BPH evolves and progresses. In conclusion, preoperative cystometrography in
      patients with BPH is valuable in that it correlated well with the clinical
      features and it can predict to some extent the outcome of obstructive symptoms
      and urinary incontinence after transurethral prostatectomy.

PMID- 7516979
TI  - A sham controlled trial of transurethral microwave therapy with subsequent
      treatment of the control group.
AB  - To investigate whether there is a significant placebo component to the
      improvements seen after 1-session transurethral microwave treatment, 40 patients
      with significant symptoms of prostatism and unequivocally benign glands were
      recruited to take part in a sham controlled study. After an active treatment the
      mean American Urological Association symptom scores improved by 63% (19.2 to 7.1)
      while after a sham treatment symptom scores improved only marginally (18.8 to
      16.2, p < 0.001). Residual volumes decreased by 50% (104 to 52 ml.) and flow
      rates increased by 2.3 ml. per second after an active treatment with no
      improvement after a sham treatment. There was a consistently greater improvement
      after an active treatment compared to a sham treatment. Patients who had received
      a sham treatment were then offered an active treatment and showed improvements
      similar to those in the original actively treated group and much greater than
      after the original sham treatment. Mean symptom scores decreased from 16.2 to 9.9
      (p < 0.004). Residual volumes decreased from 94 to 40 ml. (p < 0.005) and flow
      rates increased by 1.6 ml. per second, while these same criteria had deteriorated
      after a sham treatment. Side effects were mild and short lived, with no patients
      reporting sexual dysfunction as a consequence of treatment. Transurethral
      microwave therapy is an effective well tolerated treatment for select patients
      with benign prostatic hypertrophy and the placebo effect of treatment is minimal.

PMID- 7516978
TI  - Safety, side effects and patient acceptance of the luteinizing hormone releasing
      hormone agonist leuprolide in treatment of benign prostatic hyperplasia.
AB  - The luteinizing hormone releasing hormone agonist leuprolide was investigated in
      a double-blind, randomized, placebo-controlled study comprising 50 evaluable
      patients with moderate to severe symptoms resulting from benign prostatic
      hyperplasia. Patients received 3.75 mg. leuprolide depot or placebo as an
      injection every 28 days for 24 weeks. Hemoglobin level decreased by 0.8 gm/100
      ml. (p = 0.0052) for patients receiving leuprolide. Mean testicular volume
      decreased by 28.9% (p < 0.001) compared to placebo. Of 26 patients receiving
      leuprolide 5 had a weight gain of more than 3 kg. Almost all patients receiving
      leuprolide experienced hot flushes. Breast changes, and loss of energy and vigor
      were not more pronounced than for patients receiving placebo. Erectile function
      and sexual activity were lost during treatment. Libido also decreased but was
      still partially retained. Despite this, patients receiving leuprolide were
      generally contented with their sexual life during treatment. Side effects were
      bothersome for some patients but were reversible. Of the patients in our study
      73% expressed that they could repeat or continue treatment if that had been
      possible. The high cost of these drugs will limit their use for a benign
      condition, such as benign prostatic hyperplasia.

PMID- 7516980
TI  - Benign prostatic hyperplasia.

PMID- 7516981
TI  - Colovesical fistula: an unusual complication of prostatomegaly.
AB  - Colovesical fistula as a sequela to long-term bladder outflow obstruction is to
      our knowledge a previously unreported complication. We report a case in which
      single stage colonic resection and anastomosis with bladder repair and
      transurethral resection of the prostate resolved the condition.

PMID- 7516982
TI  - Re: The value of serial prostate specific antigen determinations 5 years after
      radiotherapy: steeply increasing values characterize 80% of patients.

PMID- 7516983
TI  - Re: BPH/obstruction special issue.

PMID- 7516984
TI  - Capsaicin-induced bladder hyperactivity in normal conscious rats.
AB  - Capsaicin, instilled intravesically in normal, unanesthetized rats induced a
      concentration-dependent bladder hyperactivity, which could be abolished by
      hexamethonium, given intra-arterially near the bladder, or by morphine
      administered intrathecally. The effect was reversible and could be repeated. The
      NK-2 receptor selective antagonist SR 48,968 and the nonselective NK receptor
      antagonist spantide, given intra-arterially near the bladder, which by
      themselves, in the concentrations used, did not affect cystometric parameters,
      both counteracted the capsaicin-induced hyperactivity, whereas the NK-1 receptor
      selective antagonist RP 67,580 failed to do so. Blockade of tachykinin receptors
      in the urinary bladder does not seem to produce changes of the micturition reflex
      associated with bladder filling in the conscious rat. However, tachykinins
      released from capsaicin-sensitive nerves by various stimuli may, through
      stimulation of NK-2 receptors, lower the threshold for initiation of the
      micturition reflex. In the rat, intravesical capsaicin may be a suitable model
      for studies of afferent activity caused by stimuli releasing peptides from
      sensory nerves in the bladder, thereby provoking bladder hyperactivity.

PMID- 7516985
TI  - Characteristics of ventricular premature contractions and their clinical course.
AB  - One hundred patients with frequent (> 1,000 beats/day) ventricular premature
      contractions (VPCs) were followed for 4 years. All of the patients, except those
      with non-cardiac death (n = 8), were classified into 3 groups based on their
      outcome. Group A consisted of 29 patients with idiopathic VPCs who survived the
      study period. Group B consisted of 49 patients with underlying diseases who
      survived the study period. Group C consisted of 14 patients who suffered cardiac
      death. There was no significant difference in the daily number of VPCs. However,
      groups B and C had more patients with Lown grade 4a or 4b VPCs than group A. The
      mean coupling interval was significantly longer in group C than in group A, and
      the standard deviation of the coupling interval was significantly larger in group
      C than in group A. Forty patients underwent serial Holter monitorings to assess
      changes in the number of VPCs. VPCs spontaneously decreased in 13 patients, while
      the other 27 patients continued to have frequent VPCs. Most of these 13 patients
      were classified as Lown grade 2. The results suggest that in patients with
      frequent VPCs, longer and more varied coupling intervals may predict a poor
      prognosis, and Lown grade 2 may predict a spontaneous regression.

PMID- 7516988
TI  - Radiotherapy for isolated increases in serum prostate-specific antigen levels
      after radical prostatectomy.
AB  - OBJECTIVE: To assess the outcome of radiotherapy in patients with increased serum
      prostate-specific antigen (PSA) levels 6 months or more after radical
      prostatectomy. DESIGN: In 27 Mayo Clinic patients, we examined the results of
      radiotherapy relative to various potentially prognostic factors during a median
      follow-up of 25 months. MATERIAL AND METHODS: All 27 patients had no nodal
      involvement at the time of prostatectomy and no clinical evidence of disease, as
      determined by history, physical examination, a radionuclide bone scan, computed
      tomography of the abdomen and pelvis, chest roentgenography, complete blood cell
      counts, and serum chemistry profiles. With use of 10-MV photons and a four-field
      approach, these patients received irradiation to the prostatic bed (60 to 67 Gy
      in 1.8- to 2.0-Gy fractions). RESULTS: Levels of PSA initially decreased in 24 of
      the 27 patients (89%). In 16 of the 27 patients (59%), the PSA level decreased to
      0.3 ng/mL or less without hormonal intervention. "Freedom from failure" (defined
      as the actuarial chance of maintaining a PSA level of 0.3 ng/mL or less) was 58%
      at 2 years and 48% at 3 years. The response to salvage radiotherapy was more
      favorable in patients with no tumor spread into the seminal vesicles and those
      with serum PSA levels of less than 1.1 ng/mL at the beginning of radiotherapy
      than in those with seminal vesicle involvement or higher PSA levels. In addition,
      patients who received radiation doses of 64 Gy or more had more favorable
      responses than did those who received lesser doses. Radiotherapy resulted in no
      severe toxicity. No patient had clinical evidence of disease at the time of this
      report. CONCLUSION: Isolated increases in serum PSA after prostatectomy indicate
      the presence of residual or recurrent disease, and radiotherapy effectively
      decreases the PSA in approximately half the cases. This result is achieved by
      eradicating residual or recurrent cancer in the postoperative tumor bed.

PMID- 7516986
TI  - Aberrant expression of membrane cofactor protein and decay-accelerating factor in
      the endothelium of patients with systemic sclerosis. A possible mechanism of
      vascular damage.
AB  - BACKGROUND: One of the main features of systemic sclerosis (SSc) is vascular
      damage, the mechanism of which is not understood. The aim of this study was to
      investigate if complement (C) regulatory molecules, membrane cofactor protein
      (MCP), decay-accelerating factor (DAF), and CD59, which normally protect
      endothelial cells from damage by autologous C, are absent or down-regulated in
      vascular endothelium of patients with SSc. A deficiency or persistent down
      regulation of the above molecules is likely to render vascular endothelium of
      these patients susceptible to damage by physiologically or pathologically
      activated C. From this point of view, expression of MCP, DAF, and CD59 was tested
      on endothelium of skin of normal subjects and patients with diffuse and limited
      forms of SSc. EXPERIMENTAL DESIGN: Punch biopsies of normal skin (N = 11) and
      lesional and non-lesional skin of patients with diffuse (N = 5) and limited (N =
      5) forms of SSc were obtained and serial sections prepared. Immunoperoxidase
      staining of these sections was carried out using four monoclonal antibodies
      (MoAbs) directed to different epitopes of DAF, four to different epitopes of MCP,
      one to CD59 and one to von Willebrand factor. von Willebrand factor served as a
      marker of endothelial cells. Besides normal skin, lesional skin of systemic lupus
      erythematosus and several inflammatory and proliferative diseases, described
      below, served as controls. RESULTS: The endothelium of normal skin strongly
      expressed all the three proteins. However, the endothelium of lesional and
      nonlesional skin of all the 10 patients with diffuse or limited forms of the
      disease tested, expressed either decreased or undetectable amounts of MCP and
      DAF. CD59 expression was normal in some patients and lower than normal in others.
      Aberrant expression of MCP, DAF, or CD59 was not found in other control
      inflammatory, connective tissue and proliferative diseases studied. CONCLUSIONS:
      In view of the common function of MCP and DAF to protect self cells from
      autologous C, their decrease or virtual absence from the endothelium of patients
      with SSc strongly suggests that this deficiency may contribute to vascular
      damage, resulting in intima proliferation and, finally, fibrosis.

PMID- 7516989
TI  - When should radiation therapy follow radical prostatectomy in the management of
      prostatic cancer?

PMID- 7516987
TI  - Hyalin degeneration is present in acute myocardial infarction.

PMID- 7516990
TI  - Pulmonary toxicity and bleomycin.

PMID- 7516991
TI  - Epidermal keratinocyte expression of inducible nitric oxide synthase in skin
      lesions of psoriasis vulgaris.

PMID- 7516993
TI  - Thalidomide and the immune system. 3. Simultaneous up- and down-regulation of
      different integrin receptors on human white blood cells.
AB  - Time-dependent changes in the surface receptor expression of various maturational
      and integrin receptors on peripheral blood cells were studied in two healthy
      human volunteers following oral applications of thalidomide (Thd). In each
      measurement the receptor density was quantified by prior calibration of the flow
      cytometer with latex beads bearing a determined number of fluorescence molecules.
      The effects observed in the course of the Thd-treatment were practically
      identical or at least very similar in both the volunteers during four different
      trials, and were in accord with previous results obtained in large-scale studies
      (68 treated animals) with non-human primates. It should be stressed that no clear
      cut changes were observed in the percentage or absolute numbers of primary
      lymphocyte subsets such as CD3, CD4 and CD20. After the first two doses of 7 mg
      Thd/kg body wt the CD18 (the common beta-chain of the beta 2-integrins) marker
      already decreased in surface density or was no longer detectable on granulocytes,
      monocytes and lymphocytes. This effect persisted throughout the treatment period
      and slowly subsided after discontinuation of treatment. With a few days lag
      phase, the surface density of CD54 (ICAM-1) on granulocytes increased and many
      cells previously not bearing this receptor newly acquired such surface markers.
      On monocytes however, the CD54 receptor was lost on many cells. Within the
      lymphocyte fraction a loss of the CD54 marker could be noted on CD4 cells but not
      on CD8 cells, where an increase of the receptor expression could be observed.
      Other markers, such as the alpha chains of the beta 1 integrins CD49b (VLA alpha
      2) and CD49d (VLA alpha 4) showed contrasting reactions to the Thd-treatment.
      Whereas a pronounced loss of the receptor density of CD49d was observed and only
      few cells with high epitope density were left in the blood at the end of the
      complete dosing schedule, no such effect was observable on cells bearing the
      CD49b epitope. A distinct reduction of the number of receptors was also
      noticeable on L-selectin (Leu8) bearing cells. On CD4 positive lymphocytes, the
      majority of the described effects on the integrin and adhesion receptors was seen
      on cells bearing the CD45R0 maturational epitope. This functional receptor is
      strongly down-regulated and the pathway of CD45RA to CD45R0 maturation is
      apparently altered by Thd-treatment. These multiple changes we observed may
      explain the large variety of therapeutic effects experienced in the treatment
      with Thd.

PMID- 7516992
TI  - Microvessel count and cerebrospinal fluid basic fibroblast growth factor in
      children with brain tumours.
AB  - Tumour growth is angiogenesis-dependent; brain tumours have more intense
      neovascularisation than other tumours and produce basic fibroblast growth factor,
      a potent angiogenic mediator. Because little is known about the release of basic
      fibroblast growth factor from brain tumours into extracellular fluids, we tested
      cerebrospinal fluid (CSF) from 26 children and young adults with brain tumours
      and 18 controls for basic fibroblast growth factor and for proliferative activity
      on cultured capillary endothelial cells. We also measured the density of
      microvessels in tumours by immunohistochemical staining. Basic fibroblast growth
      factor was detected in the CSF of 62% (16 of 26) patients with brain tumours but
      in none of the controls. Specimens with basic fibroblast growth factor stimulated
      DNA synthesis of capillary endothelial cells in vitro. Endothelial proliferative
      activity was blocked by neutralising antibodies to basic fibroblast growth
      factor. Basic fibroblast growth factor correlated with mitogenic activity in CSF
      in vitro (p < or = 0.0001), and with density of microvessels in histological
      sections (p < or = 0.005). A microvessel count of > or = 68 per 200 x field was
      associated with tumour recurrence (p = 0.005) and with mortality (p = 0.02).
      Basic fibroblast growth factor in brain tumours may mediate angiogenesis as
      measured by microvessel density in histological sections, so has potential as
      both a marker for neoplasia and a target for tumour treatments. Furthermore,
      evaluation of cerebrospinal fluid basic fibroblast growth factor, along with
      microvessel quantitation in biopsied tumours, may provide improved prognostic
      information for the management of patients with brain tumours.

PMID- 7516994
TI  - Expression of nitric oxide synthase and colocalisation with Jun, Fos and Krox
      transcription factors in spinal cord neurons following noxious stimulation of the
      rat hindpaw.
AB  - Expression of nitric oxide synthase (NOS) was investigated in neurons of lumbar
      spinal cord of adult rats following subcutaneous injection of formalin (FOR) in
      one hindpaw. NOS was visualized immunocytochemically using a specific antibody
      and by the NADPH-diaphorase reaction (NDP). In the untreated rat, NOS
      immunoreactivity (IR) and NDP were present in neurons of the superficial dorsal
      horn (sDH) predominantly in layers II-III, and in the deep dorsal horn (dDH)
      predominantly in layer X. Twenty-four hours following FOR, the numbers of neurons
      labelled for NOS and NDP and the density of NDP containing nerve fiber
      varicosities significantly increased in sDH of the ipsilateral L3-L4 segments.
      NOS-IR and NDP gave a rather congruent distribution of labelled neurons in the
      dorsal horn. In contrast, distinct NOS-IR but not NDP was visible in large
      diameter motoneurons and in the lateral spinal nucleus. Double labelling
      demonstrated that in sDH most of the NDP-reactive neurons show a close spatial
      relationship to fibers and varicosities immunoreactive for substance P and CGRP.
      These neuropeptides are considered mediators of synaptic input from nociceptive
      primary afferents. Colocalization of NDP with c-Jun, JunB, JunD, c-Fos, FosB and
      Krox-24 transcription factors was investigated in neurons of lumbar spinal cord.
      c-Jun, JunB, c-Fos and Krox-24 reached their maximal levels of expression 2 h
      after FOR and returned to basal levels after 10 h. FosB and JunD reached their
      maximal expression after 5 h, persisted up to 10 h and were still visible in 60%
      70% of the maximal number of labelled nuclei after 24 h. This persistent
      expression of transcription factors might contribute to the up-regulation of NOS
      expression between 10 h and 24 h. In a low number of NDP neurons, suprabasal
      immunoreactivity of JunB, c-Fos and Krox-24 proteins was visible up to 10 h, and
      of JunD and FosB up to 24 h in sDH neurons; c-Jun was not expressed in NDP
      labelled neurons of sDH, but, similar as JunD, showed basal colocalization in
      preganglionic sympathetic and parasympathetic neurons. In dDH, colocalization of
      Jun, Fos and Krox-24 proteins in few neurons was only observed following a second
      FOR stimulus given 24 h after the first one. Double-staining also demonstrated
      that many Jun, Fos and Krox labelled neurons are in close proximity to NDP
      labelled nerve fibers suggesting a functional relationship between expression of
      immediate-early gene encoded transcription factors and presence of nitric oxide
      in the rat spinal cord.

PMID- 7516995
TI  - Nitric oxide synthase mRNA expression in human subthalamic nucleus, striatum and
      globus pallidus: implications for basal ganglia function.
AB  - The distribution of NOS mRNA within human basal ganglia was investigated using in
      situ hybridisation histochemistry (ISHH). Greater than 95% of subthalamic nucleus
      neurons were NOS mRNA-positive, between 1.5% and 2% of striatal neurons were
      positive and scattered NOS mRNA-positive neurons were detected in the medial, but
      not lateral globus pallidus. Levels of NOS mRNA expression per neuron were
      considerably higher in the striatum than in the pallidum or subthalamus. These
      findings have implications for basal ganglia function and disease states.

PMID- 7516996
TI  - Effect of morphine on hypothalamic tyrosine hydroxylase mRNA levels in
      dopaminergic neurons and on preoptic DOPAC levels measured by microdialysis.
AB  - Morphine not only suppresses norepinephrine-induced increases in LHRH mRNA levels
      but, in these same animals, it simultaneously amplifies norepinephrine (NE)
      induced LH release. These observations suggest that NE may activate parallel
      mechanisms which independently increase LHRH mRNA levels and LHRH release and
      suggest that some of these effects could be mediated indirectly via morphine's
      action on different components of the hypothalamic dopamine (DA) system.
      Accordingly, in the present studies we examined the effects of morphine on
      various components of this dopamine system using as our index of altered DA
      neuronal activity, the changes which occur in tyrosine hydroxylase (TH) mRNA
      levels following morphine. As an ancillary index of changes which occur in
      dopamine neuronal activity, we measured, by microdialysis, the changes which
      occur in preoptic dihydroxyphenylacetic acid (DOPAC) levels after either
      subcutaneous injections or following microinfusions of morphine into the zona
      incerta (ZI). In a final study, we evaluated whether DA when given alone (icv
      infusion) or prior to icv NE would altered LH release. Single cell levels of TH
      mRNA in preoptic A15 and periventricular anterior hypothalamic A14 DA neurons
      were not affected by morphine 1, 5 and 24 h later. In contrast, within 1 h after
      morphine, TH mRNA levels in ZI A13 neurons were significantly elevated and they
      remained high at 5 nd 24 h compared to controls. Morphine also resulted in a
      significant rise in TH mRNA levels in tuberoinfundibular DA neurons (TIDA) (A12)
      within 1 h and these levels remained high to 5 h. Thereafter, by 24 h, message
      levels had returned to control values. Morphine also resulted in a rapid rise in
      plasma prolactin (Prl) with peak values occurring at 20 min and then returning to
      baseline by 90 min. When morphine was given sc it resulted, within 15 min, in a
      rapid rise in preoptic DOPAC levels and these levels continued to rise such that
      they were 217% higher than pretreatment values by 105 min. Preoptic 5
      hydroxyindoleacetic acid (5-HIAA) levels also increased by 25-75% after sc
      morphine. The microinfusion of morphine into ZI also resulted in elevated
      preoptic DOPAC but not 5-HIAA levels within 15 min. The icv infusion of DA alone
      had no effect on plasma LH whereas, NE (icv) produced a modest but significant
      increase in plasma LH. When DA was given 15 min prior to the infusion of NE,
      neither amplification nor inhibition of NE-induced LH release occurred. From
      these and other studies we conclude that the morphine-induced suppression of TIDA
      neuronal activity may allow NE to release greater amounts of LHRH from axon
      terminals in the median eminence.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7516998
TI  - Recent evolutionary history of American Onchocerca volvulus, based on analysis of
      a tandemly repeated DNA sequence family.
AB  - Polymerase chain reaction (PCR) products were characterized for a repeated
      sequence family (designated "O-150") of the human filarial parasite Onchocerca
      volvulus. In phylogenetic inferences, the O-150 sequences clustered into closely
      related groups, suggesting that concerted evolution maintains sequence homology
      in this family. Using a novel mathematical model based on a nested application of
      an analysis of variance, we demonstrated that African rainforest and savannah
      strain parasite populations are significantly different. In contrast, parasites
      collected in the New World are indistinguishable from African savannah strains of
      O. volvulus. This finding supports the hypothesis that onchocerciasis was
      recently introduced into the New World, possibly as a result of the slave trade.

PMID- 7516999
TI  - Nitric-oxide synthase assays.

PMID- 7517000
TI  - Isoforms of nitric-oxide synthase: purification and regulation.

PMID- 7516997
TI  - A conserved Streptococcus pyogenes extracellular cysteine protease cleaves human
      fibronectin and degrades vitronectin.
AB  - Streptococcus pyogenes secretes an extracellular cysteine protease that cleaves
      human interleukin 1 beta precursor to form biologically active IL-1 beta, a major
      cytokine mediating inflammation and shock. To further investigate the potential
      role of the cysteine protease in host-parasite interactions, the enzyme was
      purified to apparent homogeneity and tested for ability to degrade several human
      extracellular matrix proteins. Purified protease cleaved fibronectin, apparently
      at specific sites, and rapidly degraded vitronectin. In contrast, the protease
      did not have substantial activity against laminin. The cysteine protease also
      cleaved fibronectin from human umbilical vein endothelial cells grown in vitro.
      Allelic variation in the cysteine protease structural gene was studied in 67
      strains expressing 39 M protein serotypes and five provisional M serologic types,
      and representing 50 phylogenetically distinct clones identified by multilocus
      enzyme electrophoresis. The gene is well conserved and allelic variation is due
      solely to accumulation of point mutations. Based on predicted amino acid
      sequences, one mature cysteine protease variant would be made by clones
      expressing serotypes M2, M3, M4, M5, M6, M9, M10, M11, M12, M14, M18, M22, M23,
      M25, M27, M41, M49, M56, M59, two provisional M types, and two clones non
      typeable for M protein. Moreover, 33 of the 39 speB alleles identified encode one
      of three mature protease variants that differ from one another at only one or two
      amino acids clustered in a ten-amino acid region. All 39 alleles, and virtually
      all strains, encode a product that reacts with polyclonal antisera specific for
      purified cysteine protease. No compelling evidence was found for a primitive
      differentiation of the speB gene into two distinct classes, as has been proposed
      for M protein, opacity factor phenotype, and vir regulon architecture. The
      results demonstrate that the cysteine protease is well conserved in natural
      populations of S. pyogenes, provide additional evidence that this enzyme is
      involved in host-parasite interactions, and suggest that the protease plays a
      role in bacterial dissemination, colonization, and invasion, and inhibition of
      wound healing.

PMID- 7517001
TI  - Purification, cloning, and expression of nitric-oxide synthase.

PMID- 7517002
TI  - Measurement of iron and copper in biological systems: bleomycin and copper
      phenanthroline assays.

PMID- 7517003
TI  - Alteration in the agonist/antagonist balance of antiestrogens by activation of
      protein kinase A signaling pathways in breast cancer cells: antiestrogen
      selectivity and promoter dependence.
AB  - We find that stimulation of the protein kinase A (PKA) signaling pathway in MCF-7
      human breast cancer cells changes the agonist/antagonist activity of tamoxifen
      and related antiestrogens; it activates or enhances their estrogen agonist
      activity and reduces their ability to antagonize the effects of estradiol (E2).
      In MCF-7 human breast cancer cells which contain high levels of endogenous
      estrogen receptor (ER), the antiestrogen trans-hydroxy-tamoxifen (TOT) fails to
      stimulate transcription of the estrogen-responsive promoter-reporter constructs
      estrogen response element (ERE)-TATA-chloramphenicol acetyl transferase (CAT),
      (ERE)2-TATA-CAT, and pS2-CAT. However, when cells are treated with isobutyl
      methylxanthine plus cholera toxin (which increases intracellular cAMP
      approximately 10-fold), or with 8-bromo-cAMP, or are transfected with expression
      vectors for the PKA catalytic subunits, the transcriptional activity of the
      antiestrogen-ER complex is now increased, to levels 20-75% that of E2, and TOT
      also becomes much less effective in antagonizing the stimulation of transcription
      by E2. Although this alteration in the agonist and antagonist activity of TOT is
      observed with three promoter-reporter constructs, containing a simple TATA
      promoter or a more complex, pS2 promoter, elevation of cAMP did not enhance the
      transcription by either TOT or E2 of the reporter plasmid ERE-thymidine kinase
      CAT. Thus, this phenomenon is promoter specific. The maximal stimulatory effects
      of isobutylmethylxanthine plus cholera toxin and PKA catalytic subunits on TOT
      and E2 transcriptional enhancement were not additive, consistent with the
      hypothesis that they are both acting via stimulation of the same signal
      transduction pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517004
TI  - Involvement of RecF pathway recombination genes in postreplication repair in UV
      irradiated Escherichia coli cells.
AB  - Mutations affecting the RecF pathway of recombination (recF, recG, recJ, recN,
      recO, recQ, recR, ruvA, ruvC) were systematically introduced into two sets of
      strains: (a) uvrA and uvrA recA2020, (b) uvrA recBC sbcBC and uvrA recBC sbcBC
      recA2020. We examined: (i) the effect of these mutations on the repair of DNA
      daughter-strand gaps which are produced in the nascent DNA synthesized after UV
      irradiation, and (ii) the ability of recA2020 (a suppressor for the recF
      mutation) to suppress the UV radiation sensitivity caused by these mutations. In
      the uvrA cells, mutations in recF, recR or recO genes produced a major deficiency
      in the repair of daughter-strand gaps, whereas mutations in recJ, recG, recN,
      recQ, ruvA or ruvC genes had no effect on the repair of daughter-strand gaps. In
      both uvrA and uvrA recBC sbcBC backgrounds, the UV radiation sensitivity caused
      by recF, recG, recR, recO, ruvA, or ruvC mutations was partially suppressed by
      recA2020, whereas the UV radiation sensitivity caused by recJ, recN, or recQ
      mutations was not suppressed by recA2020. Partial suppression of the UV
      sensitivity of recG, ruvA and ruvC mutants was not observed with other
      suppressors for recF, i.e., recA441, recA720 and recA730. Taken together, these
      results further support the notion that the recF, recR and recO gene products
      (abbreviated as RecFOR) function at the same step in recombination repair,
      possible as a complex. It also suggests that this putative RecFOR complex does
      not contain proteins encoded by other genes involved in the RecF pathway of
      recombination.

PMID- 7517005
TI  - Effects of arsenic on DNA damage and repair in human fetal lung fibroblasts.
AB  - Previous studies suggest that arsenic may be both mutagenic and co-mutagenic. In
      this report, we examined the effects of sodium arsenite (As) and N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG) on unscheduled DNA synthesis (UDS) in human fetal
      lung fibroblasts (2BS cells) by 3H/14C double-labeling and liquid-scintillation
      counting techniques. Arsenic at concentrations of 1, 5 and 10 microM increased
      UDS value, indicating that arsenic directly damaged DNA and did not inhibit DNA
      repair. In addition, UDS induced by 34 microM MNNG in combination with arsenic
      was significantly increased by 3 microM As and not affected by 0.1, 0.5, 1.0 and
      5 microM As, also indicating that arsenic did not inhibit the excision and
      polymerization steps of DNA repair. Based on the results and a previous study
      that 3 microM As is more efficient than 1 and 5 microM As in the induction of DNA
      protein crosslinks, we proposed that arsenic may enhance the mutagenicity of
      other compounds by inducing DNA-protein crosslinks rather than inhibiting DNA
      repair.

PMID- 7517006
TI  - Electroporation and streptolysin O--a comparison of poration techniques.
AB  - CHO (Chinese hamster ovary), xrs5 (X-ray sensitive Chinese hamster) and HF19
      (untransformed human fibroblast) cells, were exposed to a lethal dose of the
      restriction enzyme Pvu II during electroporation or poration with the bacterial
      toxin streptolysin O. The uptake of the exclusion dye trypan blue was used as a
      measure of poration and compared with survival as measured by subsequent colony
      formation. It was assumed that any surviving cells had not been permeabilized and
      therefore did not receive any restriction enzyme. Electroporation alone proved to
      be more cytotoxic to the cells, whilst streptolysin O was more efficient at
      permeabilizing both hamster and human cells.

PMID- 7517007
TI  - Effect of deoxyribonucleosides on the hypersensitivity of human peripheral blood
      lymphocytes to UV-B and UV-C irradiation.
AB  - We have previously shown that non-cycling (unstimulated) human lymphocytes from
      normal donors show extreme hypersensitivity to UV-B irradiation, and are killed
      by an excisable lesion which is not a pyrimidine dimer or 6-4 photoproduct. In
      this paper we show that addition of the 4 deoxyribonucleosides to the medium,
      each at 10(-5) M, substantially increased the survival of non-cycling normal
      human T-lymphocytes following UV-B irradiation and substantially reduced the
      frequency of excision-related strand breaks in human mononuclear cells. Addition
      of ribonucleosides to the medium did not enhance excision-break rejoining. The
      survival of fibroblasts, of cycling T-lymphocytes and of unstimulated xeroderma
      pigmentosum T-lymphocytes was not enhanced by deoxyribonucleosides. This suggests
      that the hypersensitivity is due to reduced rejoining of excision breaks as a
      consequence of low intracellular deoxyribonucleotide pools and that it can be
      redressed by supplementation of the medium with deoxyribonucleosides or
      upregulation of ribonucleotide reductase following mitogen stimulation. We
      suggest that UV-B forms an additional DNA lesion which is not a pyrimidine dimer
      or 6-4 photoproduct, which is relatively common, and at which incision is
      particularly efficient. In fibroblasts, repair of this lesion is completed with
      high efficiency, whereas in normal unstimulated T-lymphocytes, rapid incision
      exacerbates the effects of the reduced rate of strand rejoining and leads to cell
      death.

PMID- 7517008
TI  - A comparison of the DNA-damaging, the cytotoxic and genotoxic properties of
      tetracycline in human fibroblasts in the presence and absence of light.
AB  - The reduction of the colony-forming ability, the induction of DNA strand breaks
      and DNA repair were determined in human fibroblasts after treatment with
      tetracycline (TC) in the presence and absence of light. In all experiments human
      fibroblasts were more sensitive to incubations of TC in the light than in the
      dark. Induction of DNA single-strand breaks and DNA repair were detected in the
      cells after a 1-h incubation with TC under light but not in the dark. In contrast
      to these results, TC induced single-strand breaks in isolated PM2 DNA in the
      dark, however, to a lower extent than in the presence of light. In both cases
      strand break formation was totally suppressed by adding catalase. The formation
      of a TC-derived radical by ESR and a decomposition product by UV-vis spectroscopy
      was observed in the presence and absence of light; their rate of formation in the
      dark was much smaller than in the light.

PMID- 7517009
TI  - Nomenclature of human DNA repair genes.

PMID- 7517010
TI  - DNA repair in the genomic region containing the beta-actin gene in xeroderma
      pigmentosum complementation group C and normal human cells.
AB  - The limited DNA excision repair in UV-irradiated fibroblasts from xeroderma
      pigmentosum complementation group C (XP-C) occurs in selected chromatin regions.
      The small beta-actin gene (3.5 kb) is one of these and is repaired as part of a
      large region (about 50 kb). We show here that only one of the DNA strands is
      repaired through this extended region. Several genomic fragments spanning about
      70 kb in the beta-actin region have been cloned and mapped and some have been
      examined for repair activity. Both strands of one fragment (14 kb) in the
      immediate vicinity of the gene are repaired. Transcripts associated with both
      strands are detected. In normal cells, both strands of the same fragment are
      preferentially repaired relative to the genome overall and also associated with
      transcription. The repair activity in XP-C cells associated with other defined
      DNA fragments indicates that termini for the repaired regions in either strand
      can be located. Results are consistent with those of others indicating that
      transcription promotes repair in XP-C cells and that several levels of repair
      activity, at least one coupled to transcription, occur in normal cells. We
      conclude that the beta-actin repair domain, defined in XP-C cells, comprises both
      strands of a small region (about 14 kb) in the vicinity of the beta-actin gene
      and a single strand extending through a larger region of about 50 kb. We suggest
      that a similar genomic organization for repair exists in normal cells.

PMID- 7517012
TI  - Biological inactivation of pBR322 plasmid DNA by enzyme- and radiation-induced
      single-strand damage under various conditions.
AB  - The influence of three different kinds of single-strand breaks (ssb) on the
      biological activity of plasmid DNA (pBR322) was studied. The single-strand breaks
      were produced either by gamma-irradiation (together with base and sugar damage)
      or by DNase I digestion which introduced ligatable ssb. Non-ligatable ssb--single
      strand gaps of three nucleotides in length--were generated in the nicked DNA by
      exonuclease III treatment. The biological activity (N/N(o)) of this damaged DNA
      was assessed in vivo by transformation of E. coli (CMK) repair wild-type cells.
      The activity of the enzymes of E. coli was studied in vitro by incubation in a
      protein extract of E. coli making use of an in vitro assay introduced earlier,
      which makes it possible to distinguish between enzymatic degradation (dsb
      formation) and repair of damaged plasmid DNA. The biological activity (D37) of
      DNA with non-ligatable ssb, as determined by electrotransformation, was about 56%
      lower than that of DNA with ligatable ssb. The biological activity of
      enzymatically damaged DNA is greater in calcium-treated cells than in
      electroporated cells. It is proposed that this is due to a calcium-dependent
      inhibition of nucleases. In contrast to the enzymatically damaged DNA, with gamma
      radiation-damaged DNA a calcium-dependent increase in survival was not observed.
      Therefore, calcium-dependent nucleases do not play a role in the repair of damage
      produced by gamma-irradiation. The enzyme activity data show that the single
      strand damages are either converted into dsb or repaired. A comparison of the
      efficiency of dsb formation in the extract for two of the single-strand damages
      is presented. The efficiency depends on the kind of damage and on the presence of
      cofactors, especially ATP and dNTPs.

PMID- 7517011
TI  - Stable expression in rat glioma cells of sense and antisense nucleic acids to a
      human multifunctional DNA repair enzyme, APEX nuclease.
AB  - We have cloned mouse and human cDNAs for a multifunctional DNA repair enzyme
      (APEX nuclease) having apurinic/apyrimidinic (AP) endonuclease, 3',5'
      exonuclease, DNA 3' repair diesterase and DNA 3'-phosphatase activities. To
      investigate the biological role of APEX nuclease, sense or antisense APEX RNA was
      stably expressed at a high level in cultured rat glioma cells by introducing
      plasmids (pABWN-HAPX1F for expression of sense RNA or pABWN-HAPX2R for expression
      of antisense RNA) constructed from the human APEX cDNA and an expression vector
      pABWN. Multiple copies of the construct were integrated into the glioma cells
      transfected with pABWN-HAPX1F or pABWN-HAPX2R. These transfectants showed
      markedly high expression of RNA hybridizable to human APEX cDNA, indicating the
      expression of the sense or antisense RNA. Activity blotting analyses of salt
      extracts of these transfectants showed that the sense RNA-expressed cells had
      higher AP endonuclease activity and that the antisense RNA-expressed cells had
      extremely lower AP endonuclease activity than the control cells. The APEX
      nuclease-depressed glioma cells became more sensitive to methyl methanesulfonate
      and hydrogen peroxide than the control cells or the APEX nuclease-overexpressed
      cells. The results indicate that APEX nuclease plays an important role in repair
      of DNA damage caused by these genotoxic agents. The present stable expression
      systems for the sense and antisense APEX RNAs should be useful for analyzing the
      biological functions such as an antimutagenic function of the enzyme.

PMID- 7517013
TI  - Recent advances in DNA repair, mutation and recombination. A report of the
      meeting of the British Photobiology Society, London, 20 December 1993.
AB  - The 1993 British Photobiology Society DNA Repair meeting was held at City
      University, London, on December 20th. The well supported meeting heard
      presentations covering diverse aspects of repair, mutation and recombination in
      both prokaryotes and eukaryotes. The meeting particularly aims to provide a forum
      for presentations from postgraduate and postdoctoral workers, and contributions
      were received from many of the British laboratories engaged in these fields.

PMID- 7517014
TI  - Images in clinical medicine. Pressure tracings in obstructive cardiomyopathy.

PMID- 7517017
TI  - Hamsters and interferon.

PMID- 7517016
TI  - Hamsters and interferon.

PMID- 7517015
TI  - Schizophrenia.

PMID- 7517018
TI  - [Palliative therapy in neurology].
AB  - Palliative therapy aims at increasing the quality of life in patients with a
      terminal illness. This article provides an overview of the available therapeutic
      options for the most important symptoms occurring in late-stage neurological
      disease, including restlessness, drowsiness, death-rattle, shortness of breath,
      pain, seizures, raised intracranial pressure, thirst and hunger.

PMID- 7517019
TI  - Evidence against transmission of hepatitis C virus through hemodialysis
      ultrafiltrate and peritoneal fluid.
AB  - Hepatitis C virus (HCV) infection is highly prevalent in the chronic renal
      failure population treated in dialysis units. Transmission of HCV via blood
      transfusions is becoming an increasing problem, but, nevertheless, the routes by
      which this transmission occurs are incompletely known. We have searched for the
      presence of HCV RNA by the polymerase chain reaction (PCR) in serum and dialysis
      ultrafiltrate in 12 hemodialysis and 5 continuous ambulatory peritoneal dialysis
      (CAPD) patients, all of whom were HCV-antibody-positive. Serum PCR were positive
      for HCV RNA in all the cases, whereas PCR performed on samples of hemodialysis
      ultrafiltrate or peritoneal effluent were always negative for HCV RNA. In
      addition, 13 patients tested positive for HCV antibodies and 19 out of 32
      patients sharing the dialysis monitors with 17 PCR-positive individuals remained
      negative. From these findings, we conclude that the dialysis ultrafiltrate or
      peritoneal fluid seems to be an improbable source of HCV dissemination in the
      dialysis setting. Moreover, a significant group of patients remained HCV-antibody
      negative although they shared the same dialysis machine with positive patients.
      Therefore, the importance of other sources of HCV transmission, namely blood
      contaminated material, should be emphasized.

PMID- 7517020
TI  - FK 506 for vascular permeability factor production in minimal change nephrotic
      syndrome.

PMID- 7517021
TI  - NADPH diaphorase (nitric oxide synthase) in the central nervous system of spiders
      (Arachnida: Araneida).
AB  - The distribution of NADPH diaphorase (nitric-oxide synthase) in the CNS of
      spiders was determined in 10 species of five families, applying enzyme
      histochemical technique on sections of fresh frozen, unfixed material. Positively
      reacting cells could be found only in the peripheral neuropil and along internal
      and external lamellae of all species studied. These cells were numerous and
      showed long and widespread arborizations in the ventral cord of orthognath
      species. The results obtained are discussed in view of possible glial functions
      of such cells and the relation of nitric oxide to other neurotransmitters in the
      condensed brain of the Araneida.

PMID- 7517022
TI  - Glutamic acid decarboxylase immunoreactivity in some dorsal thalamic nuclei in
      Crocodilia.
AB  - Glutamic acid decarboxylase (GAD) immunocytochemical properties of thalamic
      nuclei known to project to the telencephalon were investigated in reptiles,
      Caiman crocodilus and Alligator mississippiensis, by monoclonal antibodies to GAD
      epitopes designated as GAD-1, GAD-2 and GAD-5. GAD-immunoreactive puncta were
      observed with all three monoclonal antibodies in the following dorsal thalamic
      nuclei by avidin-biotin complex methodology: dorsolateralis anterior,
      dorsomedialis anterior, diagonalis, rotundus, reuniens pars centralis and pars
      diffusa, and the medialis complex. In general, immunoreactivity to GAD was more
      robust in Alligator than in Caiman. GAD-2 immunoreactivity was more intense than
      immunoreactivity to GAD-1 or GAD-5 at similar antibody concentrations in both
      species. Thalamic nuclei varied in the pattern and intensity of GAD (+)puncta
      staining in Caiman and Alligator. No GAD-immunoreactive neurons were observed in
      any of these seven thalamic nuclei with any GAD antibody in either species.

PMID- 7517024
TI  - Memantine selectively depresses NMDA receptor-mediated responses of ratspinal
      neurones in vivo.
AB  - The clinically used agent memantine (1-amino-3,5-dimethyladamantane) can act as
      an antagonist of NMDA (N-methyl-D-aspartate) when tested in vitro, but whether
      this applies with clinically relevant doses under in vivo conditions is not
      clear. In this study memantine has been compared with the known NMDA channel
      blocker ketamine, by intravenous administration in anaesthetized rats, for
      effects on the responses of spinal neurones both to iontophoretic administrations
      of excitatory amino acids and to peripheral noxious stimuli. Spontaneous
      activity, nociceptive responses and blood pressure were not significantly
      affected by memantine and ketamine, whereas both agents selectively reduced
      responses to NMDA.

PMID- 7517025
TI  - Evidence for an inhibitory effect of nitric oxides on neuropeptide secretion from
      isolated neural lobe of the rat pituitary gland.
AB  - The present study aims at investigating the effect of pharmacological
      manipulation of nitric oxides (NOs) formation in the rat neurohypophysis on the
      secretion of vasopressin (AVP). We found that the NO synthase antagonist L-NAME
      and free-ferrous hemoglobin (an NO inactivator) produced a transient and
      significant enhancement of basal secretion of AVP from incubated glands.
      Conversely, the NO precursor L-arginine (but not its inactive counterpart D
      arginine) antagonized the stimulatory influence of L-NAME on both AVP and
      oxytocin (OT) output. Elevation of NOs formation triggered by means of the NO
      donor SIN-1 likewise dampened spontaneous, as well as stimulated, AVP release. It
      is concluded that NOs molecules show up as potent regulators of neuropeptide
      secretion at the level of nerve terminals in the neurohypophysis.

PMID- 7517023
TI  - Dephosphorylation of tau protein from Alzheimer's disease patients.
AB  - Tau protein-prepared post-mortem from brains of Alzheimer's disease patients was
      treated with protein phosphatase 1 catalytic subunit, 2A catalytic subunit, and
      2B (calcineurin). Dephosphorylation was monitored by immunoblotting with two
      monoclonal antibodies, TAU-1 and SMI31, which recognize in tau the dephospho- and
      phospho-states, respectively, of proline-directed protein kinase phosphorylation
      sites. Out of the three enzymes tested, protein phosphatase 2A was only effective
      in dephosphorylating tau at these Alzheimer-type epitopes.

PMID- 7517026
TI  - Multiple types of tachykinin receptor mediate a slow excitation of rat spinal
      motoneurones in vitro.
AB  - Using intracellular current clamp recording from motoneurones of the neonatal rat
      spinal cord in vitro, the action of tachykinin receptor agonists was
      investigated. Test drugs included the endogenously occurring neuropeptide
      substance P and synthetic compounds, such as substance P methylester (SPMeO),
      [beta Ala8]neurokinin A4-10 ([Ala]NKA), [MePhe7]neurokinin B ([MePhe]NKB) and
      senktide. SPMeO and [Ala]NKA were used as selective agonists at NK1 and NK2
      receptors, respectively, while [MePhe]NKB or senktide were employed to activate
      NK3 receptors. In control solution, all compounds produced sustained
      depolarization with increase in input resistance although at comparable levels of
      membrane depolarization different patterns of motoneuronal firing were observed
      dependent on the type of agonist tested. In tetrodotoxin (TTX; 1 microM)
      solution, the depolarization caused by substance P or SPMeO largely persisted
      while in the majority of cells the effect of [Ala]NKA, [MePhe]NKB or senktide was
      blocked. It is suggested that NK1 receptors primarily mediated the actions of
      substance P on spinal motoneurones and that activation of NK2 or NK3 receptors,
      predominantly found on interneurones, induced motoneuronal depolarization with
      different firing patterns.

PMID- 7517027
TI  - [Significance of various examination methods in the management of prostatic
      cancer].
AB  - The authors investigated the sensitivity and specificity of four methods: rectal
      digital examination, prostate specific antigen (PSA), prostatic acid phosphatase
      (PAP) and transrectal ultrasound in the diagnosis of 100 prostate cancer and 50
      suffering in benign prostatic hypertrophy patients. In 21 patients the prostate
      cancer was proved by perineal punch biopsy and in 79 cases by biopsy and by TUR
      as well. Because of its simplicity the rectal investigation has to be first one,
      after that the PSA has to be determined. The specificity of transrectal
      ultrasound is low. The determination of PAP in addition of PSA is not necessary.

PMID- 7517028
TI  - Identification and diagnostic value of a major antibody epitope on the 12 kDa
      antigen from Echinococcus granulosus (hydatid disease) cyst fluid.
AB  - An IgG1 monoclonal antibody (MoAb), designated C9E7H8, has been produced against
      an epitope on the 12 kDa antigen of Echinococcus granulosus cyst fluid, believed
      to represent the smallest subunit of antigen B. This MoAb, raised against
      purified 12 kDa antigen eluted from a reducing SDS-PAGE gel, demonstrated strong
      binding to native sheep cyst fluid in ELISA and recognition of all three subunits
      of antigen B (at 12, 16, 23 kDa) by immunoblot under both reducing and non
      reducing conditions. Immunoblot analysis also indicated that the complementary
      epitope is conserved amongst cyst fluids from different intermediate hosts of E.
      granulosus, including fluids from cysts of two distinct strains, and is present
      in cyst fluid from E. multilocularis. The monoclonal displays binding to a cDNA
      clone, EgPS-3, which we have previously shown expresses part of the 12 kDa
      molecule. EgPS-3, expressed as a glutathione-S-transferase fusion protein, was
      successful in positive detection of 74% of cystic hydatid patients, although
      cross-reactions were observed with 25% of sera from alveolar hydatid and 22% of
      sera from schistosomiasis japonica patients. Three peptides, based on the
      predicted amino acid sequence of EgPS-3, showed increased specificity but
      slightly reduced sensitivity in the detection of antibody from E. granulosus
      patients. The predominant epitope recognized by human antibody occurs in the N
      terminal 27 amino acids (peptide 65) of EgPS-3 which also correlates with the
      location of the monoclonal antibody epitope.

PMID- 7517029
TI  - Theileria annulata sporozoite surface antigen (SPAG-1) contains neutralizing
      determinants in the C terminus.
AB  - SPAG-1 is a surface antigen on Theileria annulata sporozoites that is a candidate
      both for inclusion in a subunit vaccine and as a ligand for host cell
      recognition. We have pinpointed major neutralizing epitopes to the C terminus. To
      facilitate this we expressed SPAG-1 as a series of defined fragments in the pGEX
      system. These constructs were validated by sequencing and by their spectrum of
      reactivity with monoclonal antibody (MoAb) BA4. This MoAb recognizes the elastin
      motif VGVAPG, that is predicted to occur three times in the N terminal half of
      SPAG-1. The recombinant proteins were then tested by Western blotting with a
      neutralizing MoAb (1A7) and two neutralizing bovine sera (10T and 34A). The
      results demonstrate that 1A7 and the bovine sera react with determinants unique
      to the C terminus. We mapped the neutralizing determinant recognized by MoAb 1A7
      to a 16 residue sequence (residues 807-822) using synthetic peptides.
      Interestingly the bovine sera do not recognize the 1A7 epitope. The potential
      role of the C terminus as a ligand for host cell recognition and the implications
      for sub-unit vaccine production are discussed.

PMID- 7517030
TI  - Poorly selective cation channels in the apical membrane of A6 cells.
AB  - This paper describes a Ca(2+)-blockable, poorly selective cation pathway in the
      apical membrane of A6 epithelia. This pathway has properties that resemble the
      cation-selective channels in the toad urinary bladder and frog skin.
      Transepithelial short circuit currents (Isc) and power density spectra (PDS) of
      the fluctuations in current were recorded. The basolateral surface of the tissues
      was exposed to Cl- or SO4(2-) solutions with Na+ as the major cation. Ca(2+)
      blockable inward oriented currents and Lorentzian noise were recorded with
      isotonic (215 mosmol/kg) mucosal Cl- and hypotonic (144 mos-mol/kg serosal SO4(2
      ) solution with Na+, K+, Rb+ or Cs+ as the major mucosal cation. Experiments with
      mucosal K+ demonstrated that the cation-selective channel was markedly activated
      by serosal hypotonicity. Effects of an increased electrical driving force were
      excluded on the basis of the results obtained with microelectrode experiments and
      transepithelial voltage clamping. Cell volume expansion induced by isotonic
      replacements of serosal sucrose by glycerol or urea also activated the cation
      selective pathway. Furthermore, the presence of Cl- in the mucosal solution was a
      prerequisite for a sustained response to hypotonicity or replacements of the
      organic compounds. Moreover, we found that the cation-selective channels are
      mainly expressed in the cells during the early period of epithelial growth.

PMID- 7517031
TI  - Effect of ATP, carbachol and other agonists on intracellular calcium activity and
      membrane voltage of pancreatic ducts.
AB  - The pancreatic duct has been regarded as a typical cAMP-regulated epithelium, and
      our knowledge about its Ca2+ homeostasis is limited. Hence, we studied the
      regulation of intracellular calcium, [Ca2+]i, in perfused rat pancreatic ducts
      using the Ca(2+)-sensitive probe fura-2. In some experiments we also measured the
      basolateral membrane voltage, Vbl, of individual cells. The resting basal [Ca2+]i
      was relatively high, corresponding to 263 +/- 28 nmol/l, and it decreased rapidly
      to 106 +/- 28 nmol/l after removal of Ca2+ from the bathing medium (n = 31).
      Carbachol increased [Ca2+]i in a concentration-dependent manner. At 10 mumol/l
      the fura-2 fluorescence ratio increased by 0.49 +/- 0.06 (n = 24), corresponding
      to an increase in [Ca2+]i by 111 +/- 15 nmol/l (n = 17). ATP, added to the
      basolateral side at 0.1 mmol/l and 1 mmol/l, increased the fluorescence ratio by
      0.67 +/- 0.06 and 1.01 +/- 14 (n = 46; 12), corresponding to a [Ca2+]i increase
      of 136 +/- 22 nmol/l and 294 +/- 73 nmol/l respectively (n = 15; 10).
      Microelectrode measurements showed that ATP (0.1 mmol/l) hyperpolarized Vbl from 
      62 +/- 3 mV to -70 +/- 3 mV, an effect which was in some cases only transient (n
      = 7). This effect of ATP was different from that of carbachol, which depolarized
      Vbl. Applied together with secretin, ATP delayed the secretin-induced
      depolarization and prolonged the initial hyperpolarization of Vbl (n = 4).
      Several other putative agonists of pancreatic HCO3- secretion were also tested
      for their effects on [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517032
TI  - Guanylate-cyclase-mediated inhibition of cardiac ICa by carbachol and sodium
      nitroprusside.
AB  - We studied the role of cyclic guanosine monophosphate (cGMP) as a mediator of the
      reduction of L-type calcium current (ICa) induced by muscarinic receptor
      stimulation and by nitric oxide in isolated guinea-pig ventricular cells using
      the whole-cell patch-clamp technique. Our results show that when the level of
      cyclic adenosine monophosphate was increased by the phosphodiesterase inhibitor
      isobutylmethylxanthine (IBMX), stimulation of a pertussis-toxin (PTX)-sensitive
      muscarinic receptor by carbachol (1 microM) reduced the calcium current increase
      from 80.6 +/- 23.5% to 19.8 +/- 9.6% over the control and this effect was
      prevented by methylene blue (10 microM), an inhibitor of the soluble guanylate
      cyclase. Pipette solution containing 10 microM cGMP reduced the enhancement of
      ICa by IBMX from 121.9 +/- 11.6% to 14.2 +/- 5.4% above the control. Sodium
      nitroprusside (10 microM), a spontaneous donor of nitric oxide, and consequently
      a stimulator of soluble guanylate cyclase, also reduced IBMX-stimulated ICa from
      115.2 +/- 13.2% to 32.2 +/- 6.9% above control and the sodium nitroprusside
      effect was also suppressed by methylene blue. The latter two reagents were
      ineffective on basal ICa.

PMID- 7517034
TI  - Voltage clamping of Xenopus laevis oocytes utilizing agarose-cushion electrodes.
AB  - Two-electrode voltage clamping of expressed ion channels in intact oocytes of the
      South African clawed frog Xenopus laevis has been refined to allow stable, low
      resistance electrical access to the cytosol (50-800 k omega). Glass
      microelectrodes were filled with a cushion of 1% agarose at their tips to prevent
      KCl leakage (agarose-cushion electrodes). Insertion of these electrodes into X.
      laevis oocytes yielded stable preparations for periods of more than 1 h with a
      stable input resistance of 1-4 M omega. Furthermore, a simple modification of the
      voltage-clamp circuit (charging compensator) is described that increases the
      flexibility of arrangements for differential recording of the membrane potential
      in order to subtract voltage drops across a series resistance. The result is a
      considerable increase in the practically attainable speed of the voltage clamp
      with the conventional two-electrode arrangement. The performance of the charging
      compensator was tested on an equivalent circuit that simulates the oocyte and
      electrodes. In addition, the combination of agarose-cushion electrodes and the
      charging compensator was tested on oocytes expressing Shaker H4 currents. The
      fidelity of the voltage-clamp circuit was also verified by measuring the membrane
      potential with additional independent microelectrodes connected to a differential
      amplifier, independent of the two-electrode voltage clamp system. The system
      described here will be useful for ion channel studies in X. laevis oocytes
      requiring long-term recordings and/or measurements of large, fast ion currents.

PMID- 7517033
TI  - Tetraethylammonium block of Slowpoke calcium-activated potassium channels
      expressed in Xenopus oocytes: evidence for tetrameric channel formation.
AB  - Unitary currents were recorded from inside-out membrane patches pulled from
      Xenopus oocytes that had been injected with RNA transcribed from a cDNA encoding
      the Drosophila maxi-K channel (Slowpoke). Site-directed mutagenesis was used to
      make cDNAs encoding channel subunits with single amino acid substitutions (Y308V
      and C309P). The extracellular side of the patch was exposed to tetraethylammonium
      (TEA) in the pipette solution; unitary currents in the presence of TEA were
      compared with currents in the absence of TEA to compute the inhibition. Amplitude
      distributions were fit by beta functions to estimate the blocking and unblocking
      rate constants. For wild-type channels, TEA blocked with an apparent Kd of 80
      microM at 0 mV and sensed 0.18 of the membrane electric field; the voltage
      dependence lay entirely in the blocking rate constant. TEA blocked currents
      through C309P channels with a similar affinity to wild-type at 0 mV, but this was
      not voltage-dependent. Currents through Y308V channels were very insensitive to
      any block by TEA; the apparent Kd at 0 mV was 26 mM and the blockade sensed 0.18
      of the electric field. Oocytes injected with a mixture of RNAs encoding wild-type
      and Y308V channels showed unitary currents of four discrete amplitudes in the
      presence of 3 mM TEA; at 40 mV these corresponded to inhibitions of approximately
      80%, 55%, 25% and 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517035
TI  - Substance P inactivating enzymes in human cerebrospinal fluid.
AB  - The Km and Vmax values were determined for enzymes in human lumbar cerebrospinal
      fluid (CSF) that inactivate synthetic substance P (SP = RPKPQQFFGLM-NH2) and
      produce metabolic products. For the human lumbar CSF samples analyzed in this
      study, Km = 2.24 +/- 0.93 mM and Vmax = 0.113 +/- 0.035 nmol/ml/min (n = 10; mean
      +/- SEM) for the rate of decrease of SP. HPLC analysis of the incubated synthetic
      peptide fragments demonstrated that the primary enzymatically produced fragment
      is SP(3-11), with minor amounts in decreasing order of SP(1-4), SP(1-7), and SP(1
      9). Electrospray ionization mass spectrometry (ESI-MS) confirmed the appropriate
      molecular weights for the four peptides, SP(3-11), SP(1-4), SP(1-7), and SP(1-9).
      These data demonstrate that the primary enzyme in human lumbar CSF that acts on
      synthetic SP is a post-proline cleaving enzyme (PPCE).

PMID- 7517036
TI  - Sorting single molecules: application to diagnostics and evolutionary
      biotechnology.
AB  - A method is described that provides for detection and identification of single
      molecules in solution. The method is based on fluorescence correlation
      spectroscopy, which records spatio-temporal correlations among fluctuating light
      signals, coupled with devices for trapping single molecules in an electric field.
      This technique is applied to studies of molecular evolution, where it allows fast
      screening of large mutant spectra in which targets are labeled by specific
      fluorescent ligands. The method expands the horizon in molecular diagnostics by
      making it possible to monitor concentrations down to (less than) 10(-15) M
      without any need for amplification.

PMID- 7517037
TI  - Comparison of directional selectivity in identified spiking and nonspiking
      mechanosensory neurons in the crayfish Orconectes limosus.
AB  - We have recorded electrical activity from two identified synaptically coupled
      mechanosensory interneurons in the abdominal nervous system of the crayfish
      Orconectes limosus and have studied their responses to constant-velocity water
      jet stimuli presented from different directions. The two neurons, the ascending
      caudal photoreceptor (CPR) and the local directionally selective neuron,
      responded preferentially to stimuli delivered ipsilaterally to their dendritic
      input regions. Both neurons featured responses consisting of a phasic excitatory
      "on" response and a tonic depolarizing plateau. The different response components
      showed various degrees of directional selectivity: The initial "on" peak of the
      response was the least sensitive and the plateau was the most sensitive to
      stimulus direction. The CPR showed a sharp cut-off in responsiveness to
      contralateral stimuli, whereas the local directionally selective neuron showed a
      more gradual decrease in its directional responsiveness. This difference is a
      consequence of the feed-forward lateral inhibition that the local directionally
      selective neuron exerts on the CPR and of the threshold for initiation of action
      potentials in the CPR. A comparison of the spiking response of the CPR with its
      generator potential shows that the number and frequency of action potentials are
      a more sensitive indicator of directional preference than the generator potential
      response. The directional characteristic of the CPR is discussed as a filter
      matched to a specific spatial aspect of biologically relevant water movements.

PMID- 7517039
TI  - Developmentally regulated loss of ubiquitin and ubiquitinated proteins during
      pollen maturation in maize.
AB  - Eukaryotic cells typically contain 0.2-1.0% of their total protein as the highly
      conserved protein ubiquitin, which exists both free and covalently attached to
      cellular proteins. The attachment of ubiquitin to cellular proteins occurs
      posttranslationally by a three-enzyme pathway and results in a peptide linkage of
      the C terminus of ubiquitin either to a lysyl epsilon-amino group of a substrate
      protein or to a lysyl epsilon-amino group of a previously linked ubiquitin
      molecule. The multiple conjugation of ubiquitin to substrate proteins via
      ubiquitin-ubiquitin linkages is thought to be necessary, but not sufficient, for
      recognition and degradation by a ubiquitin-dependent protease. In higher plant
      cells the steady-state level of ubiquitinated proteins is generally constant and
      can be readily detected in all somatic tissues. In contrast, we have found that a
      developmentally regulated loss of free ubiquitin and ubiquitinated proteins
      occurs during maize (Zea mays L.) pollen maturation. This dramatic loss of
      ubiquitin correlates temporally with commitment to the gametophytic developmental
      program. Northern blot analysis indicates that the loss of ubiquitin is not due
      to low levels of ubiquitin mRNA, suggesting that a posttranscriptional regulatory
      mechanism is responsible.

PMID- 7517040
TI  - Emergence of a replicating species from an in vitro RNA evolution reaction.
AB  - The technique of self-sustained sequence replication allows isothermal
      amplification of DNA and RNA molecules in vitro. This method relies on the
      activities of a reverse transcriptase and a DNA-dependent RNA polymerase to
      amplify specific nucleic acid sequences. We have modified this protocol to allow
      selective amplification of RNAs that catalyze a particular chemical reaction.
      During an in vitro RNA evolution experiment employing this modified system, a
      unique class of "selfish" RNAs emerged and replicated to the exclusion of the
      intended RNAs. Members of this class of selfish molecules, termed RNA Z, amplify
      efficiently despite their inability to catalyze the target chemical reaction.
      Their amplification requires the action of both reverse transcriptase and RNA
      polymerase and involves the synthesis of both DNA and RNA replication
      intermediates. The proposed amplification mechanism for RNA Z involves the
      formation of a DNA hairpin that functions as a template for transcription by RNA
      polymerase. This arrangement links the two strands of the DNA, resulting in the
      production of RNA transcripts that contain an embedded RNA polymerase promoter
      sequence.

PMID- 7517038
TI  - Importance of nitric oxide for local increases of blood flow in rat cerebellar
      cortex during electrical stimulation.
AB  - The endothelium-derived relaxing factor, probably nitric oxide (NO), is a potent
      vasodilator that regulates the vascular tone in several vascular beds, including
      the brain. We explored the possibility that NO might be of importance for the
      increase of cerebral blood flow (CBF) associated with activity of the well
      defined neuronal circuits of the rat cerebellar cortex. Laser-Doppler flowmetry
      was used to measure increases of cerebellar blood flow evoked by trains of
      electrical stimulations of the dorsal surface. The evoked increases of CBF were
      frequency-dependent, being larger on than off the parallel fiber tracts,
      suggesting that conduction along parallel fibers and synaptic activation of
      target cells were important for the increase of CBF. This was verified
      experimentally since the evoked CBF increases were abolished by tetrodotoxin and
      reduced by 10 mM Mg2+ and selective antagonists for non-N-methyl-D-aspartate
      receptors. The cerebellar cortex contains high levels of NO synthase. This raised
      the possibility that NO was involved in the increase of CBF associated with
      neuronal activation. NO synthase inhibition by topical application of NG-nitro-L
      arginine attenuated the evoked CBF increase by about 50%. This effect was
      partially reversed by pretreatment with L-arginine, the natural substrate for the
      enzyme, while NG-nitro-D-arginine, the inactive enantiomer, had no effect on the
      evoked CBF increases. Simultaneous blockade of non-N-methyl-D-aspartate receptors
      and NO synthase had no further suppressing effect on the blood flow increase than
      either substance alone, suggesting that the NO-dependent flow rise was dependent
      on postsynaptic mechanisms. These findings are consistent with the idea that
      local synthesis of NO is involved in the transduction mechanism between neuronal
      activity and increased CBF.

PMID- 7517041
TI  - Life-spans of human T-cell responses to determinants from the circumsporozoite
      proteins of Plasmodium falciparum and Plasmodium vivax.
AB  - The longevity of specific human memory T-cell responses is largely unknown.
      However, a knowledge of the duration of memory is important for understanding
      immunity to an organism and for planning vaccine intervention. To address this,
      we have examined T-cell memory to malaria by determining T-cell responses by
      subjects recently exposed to peptides spanning the circumsporozoite (CS) proteins
      of two species of malaria-causing organisms, Plasmodium falciparum and Plasmodium
      vivax. Responses to vivax CS peptides by exposed Thai subjects were more frequent
      than responses by nonexposed individuals, permitting identification of
      determinants seen by vivax-induced responses. At the population level, there
      appears to be life-long memory, as the time since individuals were exposed did
      not diminish responsiveness to these determinants. In contrast, falciparum
      exposed subjects were largely indistinguishable from nonexposed controls in
      responsiveness to falciparum CS determinants. However, a single peptide (F16:
      DNEKLRKPKHKKLKQPGDGN) was recognized significantly more frequently by P.
      falciparum-exposed than nonexposed Thai subjects. T cells responsive to this
      peptide were CD450+ and produced gamma-interferon. In contrast to the response to
      the vivax determinants and the other falciparum determinants, responsiveness to
      F16 was undetectable or minimal 2 years after exposure. Our data provide the
      average life-spans of certain malaria-specific T cells and are consistent with,
      but do not prove, the hypothesis that antigenic persistence (in the form of P.
      vivax hypnozoites) correlates with persistence of human T-cell memory.

PMID- 7517042
TI  - Expression cloning of a high-affinity melatonin receptor from Xenopus dermal
      melanophores.
AB  - Using an expression cloning strategy, a high-affinity melatonin receptor cDNA has
      been isolated from Xenopus laevis dermal melanophores. Transient expression of
      the cDNA in COS-7 cells resulted in high-affinity 2-[125I]-iodomelatonin binding
      (Kd = 6.3 +/- 0.3 x 10(-11) M). In addition, six ligands exhibited a rank order
      of inhibition of specific 2-[125I]iodomelatonin binding that was identical to
      that reported for endogenous high-affinity receptors. Functional studies of CHO
      cells stably expressing the receptor cDNA showed that melatonin acting through
      the cloned receptor inhibited forskolin-stimulated cAMP accumulation in a dose
      dependent manner. Northern blot analysis showed that melatonin receptor
      transcripts are moderately expressed in Xenopus dermal melanophores. The cDNA
      encodes a protein of 420 amino acids, which contains seven hydrophobic segments.
      Structural analysis revealed that the receptor protein is a newly discovered
      member of the guanine nucleotide binding protein-coupled receptor family.

PMID- 7517043
TI  - Preimplantation single-cell analysis of multiple genetic loci by whole-genome
      amplification.
AB  - Due to the limited amount of DNA in a single diploid cell, preimplantation
      genetic diagnosis has relied on single- or dual-locus analyses in biopsied
      blastomers. We have applied single-cell whole-genome preamplification to PCR
      based analysis of multiple disease loci from the same diploid cell. This method
      allows diagnosis of multiple disease genes, analysis of multiple exons/introns
      within a gene, or corroborative embryo-sex assignment and specific mutation
      detection at sex-linked loci. A blinded study of six genetic loci was performed
      with whole-genome preamplification followed by nested PCR. Amplification was
      observed in 103 of 105 assays (98%) and a correct diagnosis was made in 98%. All
      human blastomeres were correctly diagnosed (100%) at loci where the genotype
      could be confirmed, attesting to the reliability of the technique.
      Preamplification has now been applied successfully to the analysis of the two
      major mutations responsible for Tay-Sachs disease and of a common restriction
      polymorphism in the gene responsible for hemophilia A. The fidelity and length of
      product derived from this preamplification step make it an appealing technique
      for preimplantation genetic diagnoses requiring analyses at more than one locus.

PMID- 7517046
TI  - Isolation and characterization of a soluble form of the LDL receptor, an
      interferon-induced antiviral protein.
AB  - Interferons (IFNs) act by inducing several intracellular antiviral proteins. We
      report here that IFNs also induce an extracellular soluble protein that inhibits
      vesicular stomatitis virus (VSV) infection. This protein accounts for 25%-50% of
      the total antiviral activity elicited by IFN. The antiviral protein was purified
      to homogeneity from culture supernatants of IFN-treated cells by several
      chromatographic steps, to give a single 28-kDa active polypeptide. Upon
      sequencing, this novel protein corresponded to the N-terminal ligand-binding
      domain of the human 160-kDa low-density lipoprotein receptor (LDLR). In addition,
      we find that IFN induces the cell surface LDLR and this phenomenon may explain
      previous reports on reduction of serum cholesterol in IFN-treated patients.
      Viruses produce soluble cytokine receptors that inhibit their respective
      cytokines, thereby assisting virus infection. It appears now that host cells
      employ similar molecules for the opposite role of controlling virus infections.

PMID- 7517047
TI  - The Janus kinase family and signaling through members of the cytokine receptor
      superfamily.
AB  - Many cytokines initiate cellular responses through their interaction with members
      of the cytokine receptor superfamily which contain no catalytic domains in their
      cytoplasmic domains. Irrespective, ligand binding induces tyrosine
      phosphorylation, which requires a membrane proximal region of the cytoplasmic
      domain. Recent studies have shown that members of the Janus kinase (JAK) family
      of protein tyrosine kinases associate with the membrane proximal region, are
      rapidly tyrosine phosphorylated following ligand binding and their in vitro
      kinase activity is activated. The JAKs are 130-kDa proteins which lack SH2/SH3
      domains and contain two kinase domains, an active domain and a second kinase-like
      domain. Individual receptors associate with, or require, one or more of the three
      known family members including JAK1, JAK2, and tyk2. Substrates of the JAKs
      include the 91-kDa and 113-kDa proteins of the interferon-stimulated
      transcription complex ISGF3. These proteins, when tyrosine phosphorylated,
      migrate to the nucleus and participate in the activation of gene transcription.
      Recent evidence suggests that the 91- and 113-kDa proteins are members of a large
      family of genes that are potential substrates of JAK family members and may
      regulate a variety of genes involved in cell growth, differentiation or function.

PMID- 7517045
TI  - The identification of JAK2 tyrosine kinase as a signaling molecule for growth
      hormone.
AB  - The intracellular pathways by which the binding of growth hormone (GH) to its
      receptor elicits its diverse effects have eluded investigators for many years.
      Studies showing that GH rapidly stimulates tyrosyl phosphorylation of cellular
      proteins, and that tyrosine kinase activity co-purifies with GH-GH receptor
      complexes, led us to hypothesize that activation by GH of a receptor-associated
      tyrosine kinase is an important early, and perhaps, initiating step in signal
      transduction by GH. Here, we review the work identifying JAK2 as a GH receptor
      associated tyrosine kinase that is rapidly activated by ligand binding.

PMID- 7517044
TI  - Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored
      complement regulatory protein, is a receptor for several echoviruses.
AB  - Echoviruses are human pathogens belonging to the picornavirus family. Decay
      accelerating factor (DAF) is a glycosylphosphatidylinositol (GPI)-anchored
      surface protein that protects cells from lysis by autologous complement. Anti-DAF
      monoclonal antibodies prevented echovirus 7 attachment to susceptible cells and
      protected cells from infection. HeLa cells specifically lost the capacity to bind
      echovirus 7 when treated with phosphatidylinositol-specific phospholipase C, an
      enzyme that releases GPI-anchored proteins from the cell surface, indicating that
      the virus receptor, like DAF, is a GPI-anchored protein. Although Chinese hamster
      ovary cells do not bind echovirus 7, transfectants expressing human DAF bound
      virus efficiently, and binding was prevented by pretreatment with an anti-DAF
      monoclonal antibody. Anti-DAF antibodies prevented infection by at least six
      echovirus serotypes. These results indicate that DAF is the receptor mediating
      attachment and infection by several echoviruses.

PMID- 7517048
TI  - Receptor domains involved in signal transduction of prolactin and growth hormone.
AB  - Prolactin (PRL) and growth hormone (GH) receptors are members of a superfamily
      that include receptors for a number of cytokines. GH and its receptor form an
      unusual homodimer consisting of one molecule of GH and two molecules of receptor.
      A similar homodimer of the PRL receptor is probably required for biological
      effects to be seen. Using specific assays to measure the functional activity of
      PRL and GH receptors, a 25 amino acid juxtamembrane region has been identified as
      essential but not sufficient for normal action. More detailed studies have
      limited the region to eight amino acids, rich in prolines, that is highly
      conserved in many members of the receptor superfamily. Finally, GH and PRL have
      been shown to induce the rapid tyrosine phosphorylation of an associated kinase,
      Janus kinase 2, and of the receptor itself.

PMID- 7517049
TI  - Effects of cilostazol, a cyclic nucleotide phosphodiesterase III inhibitor, on
      substance P-induced airflow obstruction and airway microvascular leakage in
      guinea pigs.
AB  - We studied the effect of cilostazol, a cyclic nucleotide phosphodiesterase (PDE)
      III inhibitor, on a substance P (SP)-induced increase in lung resistance and in
      airway microvascular leakage in guinea pigs in vivo. Four minutes after
      intravenous (i.v.) administration of cilostazol (1.5 and 5 mg/kg) or vehicle,
      Evans blue dye (20 mg/kg) was given i.v. One minute later, 30 nmol/kg SP was
      administered i.v. The SP-induced increase in lung resistance was measured for 6
      min. Following the measurement of lung resistance, microvascular leakage at the
      trachea, main bronchi and intrapulmonary airways was also examined. Cilostazol
      attenuated the SP-induced increase in lung resistance, with a significant
      inhibition at the concentration of 5 mg/kg. Five milligrams per kilogram
      cilostazol also significantly inhibited SP-induced Evans blue dye extravasation
      at the trachea and main bronchi. These results suggest that cilostazol might
      reduce airflow obstruction which is seen in diseases such as asthma through
      attenuation of bronchoconstriction and, possibly, airway edema resulting from
      airway microvascular leakage in man.

PMID- 7517050
TI  - Reverse transcriptase inhibition as prescreen for potential antiviral bioactives.
AB  - Extracts from higher plants were evaluated for inhibitory activity against avian
      myeloblastosis virus reverse transcriptase. The assay may serve as a useful
      prescreen for potential anti-HIV bioactives.

PMID- 7517051
TI  - Effect of recombinant human granulocyte colony-stimulating factor on efficacy of
      radiation therapy in tumor-bearing rats.
AB  - The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF)
      on radiation-induced neutropenia and on growth of transplanted tumors treated by
      irradiation was investigated using tumor-bearing rats as a model for radiation
      therapy. In a preliminary study using normal rats, neutropenia induced by upper
      hemi-body irradiation at 3 Gy/day 5 times a week for 3 weeks was prevented by
      consecutive subcutaneous injections of rhG-CSF at 100 micrograms/kg/day. Rats
      bearing Walker-256, a mammary tumor, were scheduled to receive upper hemibody
      irradiation at 3 Gy/day for 15 times in 3 weeks if white blood cell (WBC) counts
      were maintained above 3,000/microliters. In control tumor-bearing rats not
      receiving rhG-CSF, irradiation was often withheld because of the decrease in WBC
      counts below 3,000/microliters. In contrast, a decrease in WBC counts below
      3,000/microliters was rarely found in tumor-bearing rats injected daily with rhG
      CSF. The average number of radiation treatments in control rats and rats treated
      with rhG-CSF was about 8 and 14, respectively, out of the scheduled 15 treatments
      in 3 weeks. Treatment with rhG-CSF made it possible to complete the radiation
      therapy regimen and thus inhibit the growth of the transplanted tumor more
      effectively. These results suggest that rhG-CSF may be useful to ensure radiation
      therapy on schedule in cancer patients.

PMID- 7517053
TI  - Diverse mechanisms for regulating ribosomal protein synthesis in Escherichia
      coli.

PMID- 7517054
TI  - [Activation of thiolester bond containing proteins].

PMID- 7517055
TI  - [Development of molecular biology].

PMID- 7517052
TI  - Court holds "charting by exception" policy negligent. Case in point: Lama v.
      Borras 16F. 2d 473 PR (1994).

PMID- 7517056
TI  - Localization and inhibitory actions of galanin at the feline lower esophageal
      sphincter.
AB  - Intrinsic reflexes of the lower esophageal sphincter (LES) are mediated by
      specific arrangements of excitatory and inhibitory nerves. We have previously
      described an excitatory reflex at the feline LES mediated by a bombesin-like
      peptide (BN) which causes release of substance P (SP) to directly contract the
      LES. Galanin is a neurotransmitter in the enteric nervous system which
      colocalizes in neurons containing vasoactive intestinal peptide (VIP). The aims
      of this study were to determine: (1) the distribution of galanin at the feline
      LES; (2) the effect of galanin on basal LES tone; (3) the effect of galanin on
      agonist-induced LES contractions by BN, SP and bethanechol; and (4) the effect of
      galanin on LES relaxation induced by esophageal distension and exogenous VIP.
      Galanin-like immunoreactivity (galanin-LI) was localized in neurons that were
      widely distributed throughout the LES and adjacent organs. Galanin-LI was most
      abundant in the circular muscle, muscularis mucosa and myenteric plexus of the
      LES. In anesthetized cats, intra-arterial galanin had no effect on basal LES
      pressure in a dose range of 10(-11) to 10(-6) g/kg. Galanin (5.10(-7) g/kg)
      reduced the LES contractile response to SP by 65 +/- 8% (P = 0.0001). This
      galanin-mediated inhibition of SP was not blocked by tetrodotoxin. Galanin
      similarly decreased the LES contractile response to BN (63 +/- 7%, P = 0.005) and
      bethanechol (55 +/- 17%, P = 0.012). Galanin had no effect on the LES relaxation
      induced by esophageal distension or exogenous VIP. We conclude: (1) galanin-LI is
      present in neurons at the feline LES; (2) galanin has no effect on basal
      sphincter tone, but inhibits contractions of the LES by both direct and indirect
      agonists; and (3) galanin does not effect the LES relaxation induced by
      esophageal distension or VIP.

PMID- 7517057
TI  - [Aprotinin and extracorporeal circulation. What is the benefit? What is the
      cost?].

PMID- 7517058
TI  - [Use of high doses of aprotinin in cardiac surgery].
AB  - OBJECTIVES: To study the efficacy of aprotinin in reducing whole blood loss after
      cardiac surgery with extracorporeal circulation. PATIENTS AND METHODS: Two groups
      of patients undergoing cardiac surgery with extracorporeal circulation were
      studied. Group I (n = 51) received 2 x 10(6) KIU (kallikrein inhibiting units) of
      aprotinin upon anesthetic induction, a similar dose in the extracorporeal
      circulation priming pump, and a maintenance dose of 500,000 KIU/h until removal
      from the operating theater. Group II (n = 51) was the control group. Patients
      that had previously undergone surgery with extracorporeal circulation were
      excluded, as were those being treated with anti-coagulants or anti-aggregants.
      Data recorded were blood volume, transfusions needed in the first 24 h, and blood
      derivatives used throughout the hospital stay. Postoperative kidney function was
      also determined. The occurrence of acute myocardial infarction in patients
      undergoing myocardial revascularization was also noted. RESULTS: Group I required
      a mean of 2.40 U of concentrated red blood per patient during the first
      postoperative day, as opposed to a mean of 4.3 U in group II (p < 0.001). Blood
      loss through drains was also less in group I than in group II (431.82 vs 895.29
      ml; p < 0.001). Total blood needed during the hospital stay was 3.50 units per
      patient in group I vs 5.40 U in group II (p < 0.001). Urea and creatinine were
      similar in the two groups before and after surgery (p = NS), and there were no
      significant differences in the number of cases of acute myocardial infarction in
      the two groups (3 in group I and 2 in group II). CONCLUSIONS: Administration of
      high doses of aprotinin is an effective technique for reducing the need for whole
      blood in patients requiring extracorporeal circulation during surgery. The
      technique does not compromise kidney function or increase the risk of
      perioperative acute myocardial infarction.

PMID- 7517059
TI  - [A case of prolonged QT syndrome].

PMID- 7517060
TI  - [The "arrhythmic pattern": a new method with prognostic significance in
      myocardial infarct].
AB  - OBJECTIVES: To establish a score or arrhythmic pattern for the prediction of long
      term cardiac deaths on patients who have survived to the first acute myocardial
      infarction. PATIENTS AND METHODS: We studied prospectively 200 patients that
      survived at a first myocardial infarction and in whom ambulatory ECG monitoring
      during 24 hours between days 7th and 18th (mean 12th) from the infarction was
      performed. The mean follow-up time was 51 +/- 18 months. The number and type of
      ventricular arrhythmias were analyzed and a score was measured, accordingly with
      Castellanos and Lown's classifications. An "arrhythmic pattern" or "total
      punctuation" was defined and compared among two groups: group 1 > 65 points and
      group 2 < 65 points. RESULTS: The differential characteristics of both groups
      were: age (60 +/- 9 versus 56 +/- 10 years old; p = 0.004); hypertension (63%
      versus 29%; p < 0.001); clinic stage II-III (23% versus 11%; p = 0.02);
      echocardiographic ejection fraction (45 +/- 11% versus 50 +/- 10%; p = 0.04);
      positive exercise testing (73% versus 56%; p = 0.01); arrhythmias on the exercise
      test (15% versus 25%; p = 0.006). The long-term cardiac mortality was 25% versus
      6% (p = 0.01), with an incidence of sudden death of 11% versus 3% (p < 0.05).
      Specificity, sensibility, positive predictive value and negative predictive value
      (reference cut point of 100) were 94, 65, 71 and 91%, respectively. CONCLUSIONS:
      The use of a score of arrhythmic pattern may identify 2 groups of patients with
      different clinic profiles that probably justify a different long-term prognosis
      after a first acute myocardial infarction.

PMID- 7517061
TI  - [Hemoperitoneum supporting difficult diagnosis of diffuse hepatocarcinoma in
      liver cirrhosis].
AB  - The cases of two patients with liver cirrhosis HCV-related, admitted in our
      Department in consequence of the development of ascites, anemia and clinical
      deterioration, are reported. Both patients had all major risk factors for
      hepatocellular carcinoma and anamnestic and physical findings suggesting this
      diagnosis; nevertheless, the alpha-1-fetoprotein serum levels and the
      ultrasonographic findings were not diagnostic for primary hepatic neoplasm.
      Explorative paracentesis was diagnostic, demonstrating the presence of
      hemoperitoneum (the hematocrit ratio in the ascitic fluid was 12 and 10,
      respectively). Magnetic resonance revealed extensive diffuse hepatocellular
      carcinoma on both cases. Hemoperitoneum, in patients with liver cirrhosis, in
      face of non diagnostic levels of alpha-1-fetoprotein and ultrasonographic
      findings, can be indicative of the spontaneous rupture of a diffuse type of
      hepatocellular carcinoma.

PMID- 7517062
TI  - Simplified "landmark injection" for ICG angiography.

PMID- 7517063
TI  - Instruments for submacular surgery.

PMID- 7517064
TI  - Steroidogenic impairment after lindane treatment in male rats.
AB  - The effect on testicular steroidogenesis after lindane (delta-isomer of
      hexachlorocyclohexane) administration of 4 and 8 mg/kg, i.p. daily for 45 days to
      male mature rats was investigated. A significant decline in testicular weight of
      both test groups was observed. Cellular degeneration in Leydig cells of the 8
      mg/kg treated group was conspicuous. A sharp decline in the Leydig cell's
      population and morphological deformation were supported by the decreased
      activities of testicular hyaluronidase and 3 beta delta 5-hydroxysteroid
      dehydrogenase. A high level of testicular cholesterol and depletion of ascorbic
      acid were also responsible for steroidogenic impairment in the treated groups.
      These impairments also led to a significant diminution in serum testosterone.

PMID- 7517065
TI  - Antimicrobial factors, sialic acid, and protein concentration in whole saliva of
      the elderly.
AB  - Concentrations of salivary antimicrobial factors are well documented in children
      and young adults, but little information is available on such defense factors in
      healthy elderly persons. We determined the levels of total IgA, total IgG,
      lysozyme, lactoferrin, myeloperoxidase, salivary peroxidase, amylase, sialic
      acid, and total protein in a group of 71 subjects aged 76, 81, and 86 yr, as well
      as their correlations to paraffin-wax-stimulated salivary flow rate. Participants
      were either unmedicated (n = 67) or using medicines with no oral significance (n
      = 4). Statistically significant negative correlations existed between flow rate
      and total IgA, lysozyme, lactoferrin, sialic acid, and total protein.
      Concentrations of sialic acid and salivary peroxidase were highest in the oldest
      age group. Total IgA concentration was higher in women than in men, although men
      showed higher concentrations of sialic acid and higher sialic acid/total protein
      ratios. Subjects with poor gingival health had higher concentrations of total
      protein than did those with no need for periodontal treatment. Edentulous
      subjects with complete dentures showed significantly lower concentrations of IgG,
      lactoferrin, and myeloperoxidase than did dentate subjects. Our results suggest
      that, when compared with data from previous studies, concentrations of salivary
      antimicrobial agents do not decline with age in unmedicated elderly people.
      However, defense factors which are derived also from gingival crevicular fluid
      are decreased in the absence of teeth.

PMID- 7517066
TI  - Recent developments in diagnosis and treatment of metastatic carcinoid tumours.
AB  - In carcinoid patients a tumour of enterochromaffin cell origin is present, which
      dependent on the site of origin can result in increased serotonin production.
      Metastasized carcinoids are often diagnosed by measuring 5-hydroxyindoleacetic
      acid excretion in the urine. This excretion, however, can be influenced by food
      intake. On the other hand, serotonin measured in blood platelets is unaffected by
      food intake and, in addition, is found to be more sensitive. Therapy of
      metastasized carcinoids is directed at tumour reduction or only reduction of
      symptoms. Tumour reduction can be achieved surgically or by embolization.
      Combination chemotherapy has a maximum response percentage of about 33%. Over the
      last few years, both octreotide and interferon alpha have been used in these
      patients. They rarely result in a reduction of the tumour size (10-20%). Symptom
      reduction is achievable in most patients with these agents, however. Recently,
      increasing knowledge obtained concerning the various serotonin receptors and
      their antagonists is now being used in the treatment of patients with a
      metastasized carcinoid. In the future it is expected that the different
      modalities will be combined increasingly.

PMID- 7517067
TI  - Environmental impact of vehicular traffic in Nigeria: health aspects.
AB  - Blood lead levels were analysed and pulmonary function tests were performed on
      Nigerian traffic wardens, comprising sixty from Lagos (ages 24-52 years; 27 +/-
      6), thirteen from the sparsely populated university town of Ile-Ife (ages 22-40
      years; 27 +/- 8) and a control group of twenty-four subjects (age 19-55 years; 31
      +/- 8). Perkin-Elmer Zeeman 3030/HGA 600 AAS was used for blood analysis. The
      mean lead level in Lagos wardens was 18.1 +/- 6.4 micrograms/dl, which was
      significantly higher than the level of 10.2 +/- 2.7 micrograms/dl in Ife wardens
      and 12.9 +/- 7.0 micrograms/dl obtained in the controls (P < 0.001). However,
      there was no significant difference between the levels of blood lead in Ife
      traffic wardens and normal controls. Significant differences (P < 0.0005) in
      spirometric measurements--peak flow rate (PEFR), forced expiratory volume in 1
      second (FEV1) and forced vital capacity (FVC)--were observed between traffic
      wardens and control subjects. The noise levels measured along traffic roads
      exceeded the threshold for hearing damage.

PMID- 7517069
TI  - Metal dispersion and transportational activities using food crops as biomonitors.
AB  - The multielement (Al, Ca, Cd, Ce, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Si, and Zn) levels
      of various common vegetables (bean, broccoli, cabbage, cauliflower, lettuce,
      marrow, onion, parsnip, spinach, sprouts, sweet corn, and tomato); fruits (grape
      and strawberry); herbs (garlic, lemon balm, marjoram, mint, rosemary and
      tarragon); local pasture species and surface soils collected from a commercial
      garden centre located within a distance of 30 m of the London Orbital Motorway
      (M25) is presented. Comparative values are given from a background area, namely a
      domestic garden located in the North Yorkshire Dales National Park area. Analysis
      was undertaken by inductively coupled plasma optical emission spectrometry (ICP
      OES) and inductively coupled plasma-source mass spectrometry (ICP-MS) with
      quality control assessment using four international biological reference
      materials; BCR:CRM 62 Olive Leaves, NIST 1575 Pine Needles, NIST 1573 Tomato
      Leaves, and NIST 1572 Citrus Leaves. Inter-analytical method comparison is given
      using two methods of ICP-MS; namely conventional pneumatic nebulisation of sample
      solution, and direct solids analysis by laser ablation; and neutron activation
      analysis methods (NAA). For the elements listed there is a good precision
      obtained by ICP-MS and NAA. In particular levels of < +/- 1-10% (rsd) are
      obtained. Comparison of data with certified values and other analytical methods
      are generally of very good agreement. Lead levels in background areas ranged from
      0.0008 to 0.340 microgram/g (fresh weight) for plant material; with the lead
      magnitude greater for grasses > herbs > vegetables > cereals > fruits. Measured
      values are in good agreement with reported literature values. The lowest Pb
      values are for marrow, lettuce, tomato and sweet corn samples (approximately
      0.001-0.021 microgram/g). 'Green' leaf material levels were approximately 0.02
      0.10 microgram/g (i.e. sprouts and cabbage). Root vegetables contain higher
      levels, approximately 0.02-0.125 microgram/g (especially carrot), reflecting
      possible metal uptake from soil. The highest vegetable Pb values are for leek and
      onion (approximately 0.35 microgram/g). Background values are also provided for
      nineteen elements (Al, As, B, Ba, Br, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Rb, Se,
      Sr, V, and Zn). Exposure to motor vehicle activities at a site some 30 m from the
      M25 shows only significant increases in Pb for unwashed plant material and
      surface soils. Typically Pb levels of 40-80% can be removed by washing plant
      surfaces resulting in metal levels similar to background areas.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7517068
TI  - Elemental status of grazing animals located adjacent to the London Orbital (M25)
      motorway.
AB  - The elemental (Br, Cd, Cr, Cu, Mn, Ni, Pb, Se, V, and Zn) content of blood and
      wool or hair from animals (sheep, horses and alpacas) exposed to motor vehicle
      emissions alongside the London Orbital (M25) motorway is reported. Elemental
      values were determined by inductively coupled plasma mass spectrometry (ICP-MS)
      quality control assessment using flameless atomic absorption spectroscopy (for
      Pb, correlation coefficients of whole blood r = +0.87, and hair r = +0.82), and
      replicate (n = 10) analysis of the international reference material IAEA A13
      Animal Blood. For Pb very good agreement was obtained between ICP-MS values 0.16
      +/- 0.002 microgram/g and non-certified values 0.18 microgram/g. Only Pb and Cd
      showed significantly elevated blood levels in sheep grazing alongside the M25
      motorway when compared with control (background) animals. The range of Pb blood
      values was 0.15-0.51 microgram/ml (M25) and 0.04-0.18 microgram/ml (control),
      respectively. The elemental content of the outside (tip) end of wool samples for
      the two study groups were significantly elevated in Br, Cd, Cr, Cu, Ni, Pb, V,
      and Zn for M25-exposed animals compared with controls. Elevated Pb and Cd were
      also found in horses' and alpacas' blood or hair in animals exposed to
      transportational activities. The relationship between whole blood and outer wool
      or hair Pb showed a very highly significant correlation for sheep (r = +0.89),
      horses (r = +0.69), and alpacas (r = +0.74) grazing alongside the M25 motorway.

PMID- 7517070
TI  - Unanticipated benefits of automotive emission control: reduction in fatalities by
      motor vehicle exhaust gas.
AB  - In 1970, before the implementation of strict controls on emissions in motor
      vehicle exhaust gas (MVEG), the annual USA incidence of fatal accidents by carbon
      monoxide in the MVEG was approximately 800 and that of suicides approximately
      2000 (somewhat less than 10% of total suicides). In 1987, there were
      approximately 400 fatal accidents and approximately 2700 suicides by MVEG.
      Accounting for the growth in population and vehicle registration, the yearly
      lives saved in accidents by MVEG were approximately 1200 in 1987 and avoided
      suicides approximately 1400. The decrease in accidents continues unabated while
      the decrease in expected suicides by MVEG reached a plateau in 1981-1983. The
      reasons for this disparity are discussed. Juxtaposition of these results with the
      projected cancer risk avoidance of less than 500 annually in 2005 (as compared
      with 1986) plainly shows that, in terms of mortality, the unanticipated benefits
      of emission control far overshadow the intended benefits. With the spread of MVEG
      control these benefits will accrue worldwide.

PMID- 7517071
TI  - Meniscal ossification. II. The normal pattern in the tiger knee.
AB  - Examination of knee menisci of Bengal tigers revealed ossicles within the
      cartilaginous anterior horn of each medial meniscus. This ossification was not
      evident in the neonatal animal, but was present in animals aged 20 months or
      older. The ossicle appeared prior to the completion of skeletal maturation at the
      knee, and was composed of normal remodeling trabecular bone. While most animals
      had a single, variably sized ossicle, multiple ossicles also occurred. The
      meniscal cartilage apposed to the femoral articulation exhibited a distinct
      columnar pattern in the region of the ossicle, in contrast to the non-columnar
      pattern throughout the bulk of the meniscus, including the ossicle side apposed
      to the tibial plateau. In this particular large mammalian species medial meniscal
      ossification appears to be a normal anatomical variation that progressively
      develops following birth, and may serve as a model for the phylogenetic
      (developmental) theory of etiology.

PMID- 7517072
TI  - Contralateral haemorrhagic pulmonary metastases ("choriocarcinoma syndrome")
      after pneumonectomy for primary pulmonary choriocarcinoma.

PMID- 7517073
TI  - Non-specific fluorescent whitener stains in the rapid recognition of pulmonary
      dirofilariasis: a report of 20 cases.
AB  - BACKGROUND: Solitary lung nodules in humans caused by the dog parasite
      Dirofilaria immitis are steadily increasing in number. The organisms can be
      easily missed in haematoxylin and eosin stained tissue when they are degenerated
      and pale staining. METHODS: The value of Tinopal CBS-X (TCBS-X) and Calcofluor
      white (CFW), two rapid, inexpensive, simple non-specific fluorescent whitening
      stains, were assessed in the identification of these worms. Deparaffinised
      rehydrated tissue slides prepared from the pulmonary nodules were stained for one
      minute in 1% w/v aqueous solutions of TCBS-X or CFW, counterstained,
      coverslipped, and viewed with a fluorescent microscope. RESULTS: The stains
      demonstrated the intact worm and worm fragments in 20 cases of pulmonary
      dirofilariasis collected from hospitals in Houston. The filariae and fragments of
      filariae stained bright green while the background tissue stained red,
      delineating the internal structures of the worm. CONCLUSIONS: Dirofilariasis
      should be included in the differential diagnosis of subpleural masses, and non
      specific fluorescent whitening stains can help in the rapid recognition of the
      fragmented organism in cytological or surgical material.

PMID- 7517074
TI  - Masking of heparin activity in the activated coagulation time (ACT) by platelet
      procoagulant activity.
AB  - The effect of platelet procoagulant activity in the Activated Coagulation Time
      (ACT) was measured in whole blood anticoagulated with various levels of heparin
      before or after reversal with protamine. Similar studies were carried out on
      blood anticoagulated with hirudin to distinguish procoagulant activity from
      heparin neutralization in platelet preparations. At 0.5-1.0 units/mL antithrombin
      activity with heparin or hirudin, the ACT was lowered progressively by the
      addition of increasing concentrations of lysed platelets to as much as 20 seconds
      below the baseline clotting time obtained with unanticoagulated blood samples.
      Neutralization of higher concentrations of heparin with protamine produced an ACT
      below baseline in the presence of lysed platelets. Aprotinin (400 KIU/mL)
      prolonged the ACT slightly in heparinized whole blood, but did not prevent the
      lowering of the ACT by lysed platelets to baseline or below. Recirculation of
      heparinized whole blood in a simulated cardiopulmonary bypass circuit generated
      platelet microparticles detected by flow cytometry. An increase in platelet
      microparticles was associated with a decrease in the amount of protamine needed
      to reach the baseline ACT in blood samples removed from the circuit at various
      time points during recirculation. A chromogenic anti-Factor Xa assay of heparin
      did not show a change with increasing microparticle concentration during
      recirculation. These findings indicate a masking of heparin activity by the
      procoagulant activity of platelet membrane microparticles that could affect
      reversal of heparin based on the ACT.

PMID- 7517075
TI  - Myotoxin a reduces the threshold for calcium-induced calcium release in skeletal
      muscle.
AB  - Myotoxin a, isolated from the venom of the prairie rattlesnake Crotalus viridis
      viridis, induces necrosis in skeletal muscle. In isolated organelles, it has been
      reported that myotoxin a reduces Ca2+ uptake into the sarcoplasmic reticulum. The
      effects of the toxin on Ca2+ regulation were examined in heavy sarcoplasmic
      reticulum fractions from human and equine skeletal muscle. Ca2+ uptake and
      release (the threshold of Ca(2+)-induced Ca2+ release) were examined by dual
      wavelength spectrophotometry. The toxin lowered the threshold of Ca(2+)-induced
      Ca2+ release in a dose-dependent manner (1-10 microM) and this effect was
      antagonized by ruthenium red, a Ca2+ release channel blocker. Ca2+ uptake into
      equine heavy sarcoplasmic reticulum was not decreased by myotoxin a (10 microM)
      when Ca2+ release was blocked by ruthenium red. [3H]Ryanodine binding to equine
      heavy sarcoplasmic reticulum was converted from a relatively low affinity state
      to a higher affinity state by myotoxin a. These results suggest that the dominant
      effect of myotoxin a is to increase the Ca2+ sensitivity for the opening of the
      calcium release channel (ryanodine receptor). Myotoxin a may prove to be a useful
      tool to probe the modulation of calcium release in sarcoplasmic reticulum
      fractions.

PMID- 7517076
TI  - The antimicrobial activities of cyclosporine, FK506, and rapamycin.

PMID- 7517077
TI  - Cardiac allograft atherosclerosis in the rat. The effect of histocompatibility
      factors, cyclosporine, and an angiotensin-converting enzyme inhibitor.
AB  - Cardiac transplant atherosclerosis is thought to result from immune-mediated
      vessel wall injury. The present experiments were designed to test whether CsA
      alone or in combination with the ACE-inhibitor cilazapril has any effect on graft
      atherosclerosis in a rat cardiac transplant model. Cardiac grafts were
      transplanted heterotopically into either syngeneic or allogeneic recipients and
      followed by daily palpation; long-surviving grafts were removed after 100 days
      and the extent and degree of atherosclerosis was assessed using computerized
      morphometry. Atherosclerosis was more extensive in grafts removed from untreated
      allogeneic recipients compared with syngeneic recipients; CsA treatment increased
      the extent of atherosclerosis in syngeneic transplants. The extent and degree of
      vascular occlusion in allogeneic grafts from recipients treated with 15 mg/kg of
      CsA every other day was not different from that in grafts removed from recipients
      that received initially higher CsA doses. Cilazapril had no effect on the extent
      of graft atherosclerosis but decreased the degree of luminal narrowing in grafts
      from CsA-treated recipients significantly. Some grafts showed neovascularization
      in the subendocardial region adjacent to organized intraventricular clots,
      suggesting the release of angiogenic factors from such clots; such growth factors
      may contribute to the atherosclerotic vessel wall reaction in this model. We
      conclude that CsA promotes the development of graft atherosclerosis in
      heterotopically transplanted syngeneic cardiac grafts in the rat. We furthermore
      found that cilazapril has a beneficial effect on the degree of atherosclerosis in
      CsA-treated recipients.

PMID- 7517078
TI  - The direct effect of FK506 and rapamycin on interleukin 1(beta) and
      immunoglobulin production in vitro.

PMID- 7517080
TI  - Rejection and hepatitis in liver transplants.

PMID- 7517079
TI  - Pediatric intravenous FK506--how much are we really infusing?

PMID- 7517081
TI  - [Control over prostatic functional activity].
AB  - The investigation of the tendency in the development of benign hyperplasia of the
      prostate is a crucial point in decision on the treatment initiation, schedule and
      policy. In view of this, the knowledge of the intensity of cellular proliferation
      and secretion, i.e. prostatic functional activity, in line with detrusor
      assessment is held essential. Optimal criteria of this value can be obtained by
      histological examination of prostatic biopsies, investigation of androgen and
      estrogen receptors in distant adenomatous nodes, by comparison of various
      biochemical ingredients in prostatic secretion. Twelve biochemical ingredients of
      prostatic secretion were studied in patients of the control group, in those with
      prostatic stones, adenoma, chronic prostatitis. The treatment included either
      androgenic, or antiandrogenic, or estrogenic therapy. Prostatic secretion
      biochemistry analyzed mathematically showed fluctuations in zinc ions
      concentration which appeared most significant. It is inferred that zinc ion
      concentration in prostatic secretion must be considered a significant means of
      overall evaluation of prostatic function able to represent the capacity of
      glandular epithelium for response to androgenic stimulation or estrogenic
      (antiandrogenic) inhibition of secretory and proliferative processes.

PMID- 7517082
TI  - [Transurethral hyperthermia in the treatment of prostatic adenoma].

PMID- 7517085
TI  - [Cryotherapy].
AB  - Cryotherapy is defined as cooling of definitive parts of the body by means of ice
      packs, ice cubes, ice water or ethylchloride sprays. It is used in the treatment
      of a range of conditions including spasticity and hypertonus of the muscles, soft
      tissue lesions, arthritises, edema and pain. The known physiological effects and
      clinical efficacy associated with cooling are considered. Further research i.e.
      randomized, controlled studies in the field of clinical application is high
      lighted.

PMID- 7517083
TI  - [The antiviral action of recombinant forms of the human T-lymphocyte CD4
      receptor].
AB  - A recombinant protein containing the first 179 N-terminus amino acids of human T
      lymphocyte CD4-receptor was synthesized in E. coli cells. This recombinant
      protein was shown to interact with OKT4A and Leu3a monoclonal antibodies
      competing with HIV gp120 glycoprotein for binding with the native CD4 receptor.
      Experiments in vitro in human T-lymphocyte cultures showed that the recombinant
      CD4-protein in concentrations of 1 to 10 micrograms/ml inhibited the virus
      induced syncytium formation, HIV replication in cell culture, synthesis of HIV
      reverse transcriptase and other virus-specific proteins, that is, behaved as a
      HIV inhibitor.

PMID- 7517084
TI  - [The determination of the antigenic activity of recombinant virus-specific
      polypeptides from the herpes simplex virus types 1 and 2 and their use in
      immunoenzyme analysis].
AB  - The structural and nonstructural recombinant proteins of HSV type 1 and type 2
      were expressed in E. coli by fusion with cro-beta-galactosidase proteins. These
      proteins containing amino acid sequences of ICP4, ICP27, ICP47, ICP22, major
      capsid protein and major DNA-binding proteins of HSV types 1 and 2 reacted in
      immunoblotting with the corresponding anti-HSV sera from hyperimmune rabbits. The
      nonstructural recombinant proteins can be used for enzyme immunoassay detection
      of HSV1 or HSV2 type-specific antibodies in sera from patients with acute HSV
      infection.

PMID- 7517087
TI  - High, not low, amylase and lipase levels indicate severe acute pancreatitis!
AB  - Serum amylase, lipase and C-reactive protein (CRP) levels upon and CRP again
      within 72 hours after admission were estimated in 115 consecutive patients with
      acute pancreatitis and correlated with contrast-enhanced computed tomography (CT)
      results performed within 72 hours after admission and scored for morphological
      changes and necroses. Serum enzyme levels > or = 3 times the upper limit of
      normal and CRP levels > or = 10 times on admission and maximal CRP levels > or =
      10 times within 72 hours after admission significantly correlated with severe
      pancreatic morphological changes. Thus, contrary to previous belief, high, not
      low, enzyme levels indicate severe acute pancreatitis. Furthermore, maximal CRP
      levels > or = 10 times the upper limit of normal within 72 hours in all patients
      and amylase admission levels of > or = 3 times the upper limit of normal in
      alcoholics were significantly indicative of pancreatic necroses. Thus, serum
      enzyme estimation upon, and maximal CRP levels within 72 hours after, admission
      may help the clinician to evaluate the severity of acute pancreatitis when
      imaging procedures are not immediately available.

PMID- 7517088
TI  - Serine/threonine phosphatases play a role in stimulus-secretion coupling in
      pancreatic acinar cells.
AB  - The role of serine/threonine phosphatases in Ca2+/IP3- and cAMP- mediated
      stimulus-secretion coupling was investigated in isolated pancreatic acinar cells.
      Cyclosporine A, an inhibitor of type 2b serine/threonine phosphatases, maximally
      reduced CCK-8-stimulated amylase secretion by 33%. In contrast, the secretory
      response to secretin or PACAP-(1-27) was not significantly altered by
      cyclosporine A independent of the secretagogue-concentration okadaic acid
      significantly reduced amylase release, induced by Ca2+/IP3-mediated- (CCK-8) or
      cAMP-mediated agonists (secretin, PACAP-(1-27), VIP) at concentrations that
      primarily inactivate type 1 and 2b phosphatases. Calyculin A, another type 1 and
      2a phosphatase inhibitor, had a similar inhibitory effect on CCK-8-, secretin- or
      PACAP-(1-27)-induced secretion. In permeabilized acini, cyclosporine A reduced
      calcium-induced amylase release by 20%, whereas okadaic acid and calyculin A had
      an inhibitory effect by 55% and 52%, respectively. The ultrastructure of CsA
      incubated acinar cells was not different from vehicle-incubated control lobules.
      In contrast, incubation with okadaic acid for 60 min resulted in morphological
      alterations of the Golgi apparatus, leading to a fragmentation of Golgi cisternae
      into small vesicles. Our data suggest a role of type 1 and 2b phospatases in
      stimulus-secretion coupling of both signal-transduction pathways in pancreatic
      acinar cells. These phosphatases might also be important for the maintenance of
      pancreatic cellular ultrastructure.

PMID- 7517086
TI  - [Combined treatment of metastatic endocrine tumors of the gastrointestinal tract
      with octreotide and interferon-alpha].
AB  - 14 patients with metastatic endocrine gastro-entero-pancreatic carcinoma (6
      patients with Carcinoid-syndrome, 3 with gastrinoma and 5 with non-functioning
      tumor) have been treated with Octreotide 3 x 200 micrograms/die plus Interferon
      Alpha 3 x 5 Mio U/week after documented tumor progression during preceding
      Octreotide-monotherapy. 6 out of 14 patients responded favourable to the
      treatment: one patient with partial regression and 5 patients with stillstand of
      tumor growth. In only one patient initial tumor stillstand for 6 months was
      followed by tumor progression whereas in five patients a beneficial effect on
      tumor growth could be documented up to 34 months. Inhibition of tumor growth and
      tumor progression was not necessarily paralleled by respective changes in
      peripheral hormone levels. These results should initiate a controlled prospective
      study to prove the hypothesis that in patients with metastasized endocrine gastro
      entero-pancreatic tumors the combination of Octreotide and Interferon-Alpha is
      superior to monotherapy with Octreotide or Interferon-Alpha and to identify those
      patients who respond to this combined therapy.

PMID- 7517089
TI  - Epidermal growth factor inhibits amylase secretion and activation of
      phospholipase C in response to calcium-mobilizing secretagogues in rat pancreatic
      acini.
AB  - We recently showed that epidermal growth factor (EGF) inhibits cholecystokinin
      octapeptide (CCK-8)-induced activation of phospholipase C and amylase release in
      isolated rat pancreatic acini. In the present study the effect of EGF on amylase
      release and inositol 1,4,5-trisphosphate (1,4,5-IP3) production in response to
      other calcium-mobilizing secretagogues, i.e. bombesin and carbachol, was examined
      in isolated pancreatic acini. EGF (17 nM) inhibited bombesin (100 nM)-stimulated
      amylase secretion from 10.3 +/- 1.7% to 0.8 +/- 1.6% of total above basal.
      Different from CCK-8, EGF reduced amylase release at both submaximal (< or = 1
      microM) and supramaximal (> 1 microM) carbachol concentrations. Moreover, EGF (17
      nM) inhibited bombesin-, carbachol-, and CCK-8-induced 1,4,5-IP3-production at
      five seconds after beginning of the incubation by 81 +/- 19%, 65 +/- 15%, and 60
      +/- 12%, respectively. In conclusion, these results show that EGF inhibits
      amylase secretion in response to diverse calcium-mobilizing secretagogues in the
      exocrine pancreas and suggests that this inhibition is mediated by inhibition of
      phospholipase C.

PMID- 7517090
TI  - Effect of short-term pancreatico-biliary duct obstruction with intraductal
      hypertension on subcellular organelle fragility and pancreatic adenylate energy
      metabolism in rats: protective effect of a new protease inhibitor, E-3123.
AB  - Blockage of the rat pancreatico-biliary duct (PBDO) for 4 hours and secretin
      infusion (0.2 CU [Clinical Unit]/kg/hr) caused significant rises in portal serum
      amylase, cathepsin B levels, pancreatic water content, and pancreatic amylase
      content as well as lysosomal and mitochondrial fragility. Impaired pancreatic
      adenylate energy charge levels were also noted. These changes tended to continue
      for 12 hours after the release of PBDO and disappeared after 24 hours. All the
      changes induced by PBDO with secretin infusion were no longer observed at 48
      hours. The administration of a new potent protease inhibitor, E-3123 at a dose of
      5 mg/kg/hr during PBDO markedly attenuated all the parameters examined, exerting
      a significant protective effect on acinar cells in this model. These results
      indicate the important roles of subcellular organelle fragility and impaired
      pancreatic energy metabolism in the pathogenesis of pancreatic injuries induced
      by common channel obstruction with intraductal hypertension, and also indicate
      the possible usefulness of E-3123 in the treatment of acute pancreatitis such as
      gallstone pancreatitis.

PMID- 7517091
TI  - Staining of cerebral amyloid plaque glycoproteins in patients with Alzheimer's
      disease with the microglia-specific lectin from mistletoe.
AB  - Glycoconjugates in the amyloid plaques in the cerebral cortex of patients with
      Alzheimer's disease were stained with a lectin from mistletoe (ML-I). This lectin
      selectively stains microglial cells which can be found in the centre of many
      plaques. Since the terminal carbohydrate moieties of some but not all of the
      plaques, which mainly consist of beta A4 protein, are identical to those of the
      microglial cells it is concluded that glycoproteins within these plaques have
      been synthesised by the microglial cell. These microglia deposited glycoproteins
      may be of importance for the formation of mature amyloid plaques.

PMID- 7517093
TI  - The visual outcome of peripapillary choroidal neovascular membranes.
AB  - Twenty eyes with age related peripapillary choroidal neovascular membranes were
      studied retrospectively to establish visual outcome in relation to treatment with
      argon laser, position and size. There was no statistical difference in final
      visual acuity in relation to laser treatment, size of membrane, nor position of
      the membrane at presentation. Despite these findings, there is evidence that
      laser treatment may delay the progression of visual loss.

PMID- 7517092
TI  - Comparative study of spinal cord ubiquitin expression in post-poliomyelitis and
      sporadic amyotrophic lateral sclerosis.
AB  - This study addresses the suggested possible pathogenetic relationship between the
      late-onset muscular atrophy in patients with the prior diagnosis of poliomyelitis
      and amyotrophic lateral sclerosis (ALS). For this purpose we applied
      immunohistochemical techniques to determine the presence of pathological
      structures that were stained for ubiquitin (a protein involved in degenerative
      processes) in the spinal cords of patients with a history of poliomyelitis and
      compared the results with those of ALS, a condition in which cytoplasmic
      ubiquitin-positive inclusions are invariably found in the anterior horn cells.
      Our results indicate that post-poliomyelitis patients have no ubiquitin-reactive
      inclusion bodies in these cells; however, some immunopositive globular and cord
      shaped structures are seen in less-affected areas. Similar structures were also
      found in the spinal cords from patients with ALS and from normal individuals. Our
      findings would suggest that the pathogenesis of late muscular atrophy in post
      poliomyelitis patients is dissimilar to that of ALS.

PMID- 7517094
TI  - Topical nasal sprays: treatment of allergic rhinitis.
AB  - Topical nasal sprays, especially steroids, have regained favor as treatment for
      allergic rhinitis. Nasal steroids are widely used and are as safe and effective
      as antihistamines in controlling symptoms of rhinitis. However, if improperly
      used, steroids can have side effects. It is essential that patients learn correct
      techniques for administering nasal steroids and understand complications that can
      result from nasal steroid use. New steroid drugs, such as budesonide, tripedane
      and fluticasone, are being evaluated and will be available in the near future.
      Other topical drugs, such as cromolyn and ipratropium, are also effective. Over
      the-counter decongestants are helpful in reducing nasal congestion and allowing
      other topical medicines to penetrate effectively into the nasal cavity, but their
      use should be limited to no more than three days. Prolonged use of topical nasal
      decongestants has no place in the treatment of allergic rhinitis and can be
      associated with significant side effects.

PMID- 7517095
TI  - Percutaneous valvuloplasty to relieve stenosis of a bioprosthetic tricuspid valve
      in a patient with bacterial endocarditis.

PMID- 7517096
TI  - Observations on the reliability of the Ashman phenomenon.

PMID- 7517098
TI  - Low formation of nitric oxide in polymorphonuclear cells in unstable angina
      pectoris.

PMID- 7517097
TI  - Supernormal atrial conduction and its relation to atrial vulnerability and atrial
      fibrillation in patients with sick sinus syndrome and paroxysmal atrial
      fibrillation.
AB  - The purpose of this study was to evaluate prospectively the relationship between
      supernormal atrial conduction (SNC) and the atrial vulnerability to fibrillation
      in patients with sick sinus syndrome (SSS) and paroxysmal atrial fibrillation
      (PAF). Programmed atrial stimulation was performed in 32 age-matched control
      patients (group I), 26 with SSS but without tachyarrhythmias (group II), and 24
      with both SSS and PAF (group III) to assess some determinants of atrial
      vulnerability, SNC, and atrial fibrillation inducibility. Supernormal atrial
      conduction was observed in 20 (63%) patients of group I, 12 (46%) patients of
      group II, and 5 (21%) patients of group III (group I vs group III; p < 0.002).
      The SNC zone was 46 +/- 44 msec in group I, 36 +/- 42 msec in group II, and 12 +/
      24 msec in group III. (group I vs group III; p < 0.001). The absence of SNC
      showed a specificity of 89% and a positive predictive accuracy of 79% in
      predicting inducibility of atrial fibrillation. The sensitivity was 33% and the
      negative predictive accuracy was 52%. The SNC zone showed a significant inverse
      correlation with P wave duration (r = -0.32; p < 0.003), intraatrial conduction
      time (r = -0.28; p < 0.02), and maximum conduction delay (r = -0.23; p < 0.05).
      The maximum decrease in conduction time during supernormal conduction showed a
      significant inverse correlation with P wave duration (r = -0.27; p < 0.02),
      intraatrial conduction time (r = -0.26; p < 0.02), and with the maximum
      conduction delay (r = -0.27; p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517099
TI  - Sjogren's syndrome without mixed cryoglobulinemia is not associated with
      hepatitis C virus infection.
AB  - OBJECTIVES: Hepatitis C virus infection has been associated with the formation of
      autoantibodies. Furthermore, several autoimmune and immune-complex mediated
      disorders have been proposed to be associated with hepatitis C virus infection.
      The best documented of these associations is between hepatitis C virus infection
      and essential mixed cryoglobulinemia. Essential mixed cryoglobulinemia is itself
      frequently associated with Sjogren's syndrome, and hepatitis C virus infection
      has been reported to be accompanied by lymphocytic sialadenitis and by
      xerophthalmia. We therefore searched for hepatitis C virus RNA and antibodies in
      48 patients with SS-A/SS-B autoantibodies. METHODS: Patients with both SS-A and
      SS-B autoantibodies were included if stored serum samples and medical records
      were available. No patients had clinically apparent chronic liver disease, and no
      patients had cryoglobulinemia. Six patients (group 1) had abnormally high
      aminotransferase values on one or more occasion, a history of acute hepatitis, or
      blood product exposure through transfusion or intravenous drug use. In 18 cases
      (group 2) no liver disease could be established, but there was insufficient
      information to exclude it. The 24 remaining patients (group 3) had no risk
      factors for liver disease, no known history of acute or chronic liver disease, a
      normal physical examination for signs of chronic hepatitis, and repeatedly normal
      aminotransferase values. Antibody to hepatitis C virus was determined by RIBA-2
      (Chiron Corp, Emeryville, CA). The samples were tested for hepatitis C virus RNA
      after polymerase chain reaction amplification. RESULTS: No patient had detectable
      antibody to hepatitis C virus; 47 were negative, and one sample from group 1 was
      indeterminate. No patients were positive for hepatitis C virus RNA. CONCLUSIONS:
      We conclude that our patients with Sjogren's syndrome, without cryoglobulinemia
      and with detectable SS-A/SS-B autoantibodies, do not have clinically apparent
      liver disease, hepatitis C viremia by polymerase chain reaction, or antibodies to
      hepatitis C virus by second-generation testing using RIBA-2.

PMID- 7517101
TI  - Pharmacist's international experience puts pain medications in a new light.

PMID- 7517100
TI  - A case of syncytial giant-cell hepatitis treated with an extracorporeal liver
      assist device.
AB  - Syncytial giant cell hepatitis (SGCH) has recently been reported to be a cause of
      severe hepatitis, with little chance of patient recovery without orthotopic liver
      transplantation. We have recently seen a patient with multisystem disease and
      histologic features of SGCH. Upon reaching stage IV coma, she was treated with an
      extracorporeal liver assist device containing 200 g of cultured liver cells.
      There was an immediate improvement in her galactose elimination capacity, and her
      own liver recovered to the point that therapy could be discontinued after 58 h.
      The patient recovered slowly from her multisystem disease and was discharged with
      mildly elevated transaminases and biochemical evidence of cholestasis. All
      laboratory values are normal at 2 yr, and the patient appears to have no sequelae
      of her disease.

PMID- 7517102
TI  - Doing occupational therapy: dimensions of satisfaction and dissatisfaction.
AB  - OBJECTIVES: A phenomenological study was conducted to gain understanding of the
      nature of the lived experience of doing occupational therapy. METHOD: One hundred
      and forty-eight occupational therapists nationwide were asked to describe
      especially satisfying and dissatisfying experiences of practice. The resulting
      narrative data were analyzed with dimensional analysis techniques. RESULTS: With
      the metaphor of therapy as story, three overarching dimensions of practice were
      derived from the narrative data: Change, Community, and Craft. The dimension of
      Change is strongly related to the ending or outcome of the story, Community
      encompasses the harmony or disharmony of the interrelationships in the shared
      story, and Craft includes both the skills of therapy and the broader core
      experience of doing therapy. CONCLUSION: These findings are complementary to the
      three-track mind discussed in the clinical reasoning study and contribute further
      to our understanding of the experience of doing occupational therapy.

PMID- 7517104
TI  - Fibrosarcoma versus fibromatoses and cellular nodular fasciitis. A comparative
      study of their proliferative activity using proliferating cell nuclear antigen,
      DNA flow cytometry, and p53.
AB  - We analyzed the proliferative activities, immunoreactivity of the p53 protein,
      and aneuploidy in patients with benign and malignant fibrous lesions, including
      19 with nodular fasciitis (cellular type) (6-88 years old, mean 42.9), 11 with
      abdominal fibromatoses (22-74 years old, mean 37.9), 13 with extraabdominal
      fibromatoses (2-38 years old, mean 19.5), and 23 with fibrosarcomas (adult type:
      16-71 years old, mean 47.3; infantile type: 3 months to 9 years, mean 2.9) using
      immunohistochemistry to determine proliferating cell nuclear antigen (PC10) and
      p53 protein (CM1) as well as performing DNA flow cytometry. The proliferating
      cell nuclear antigen (PCNA) score was measured as the ratio of PCNA-positive
      nuclear size/total nuclear size determined by an image analysis computer system.
      The distribution pattern of the PCNA-positive cells was uneven in each instance
      of nodular fasciitis, in contrast to the distribution in abdominal fibromatosis,
      extraabdominal fibromatosis, and fibrosarcoma. Both fibrosarcoma (28.4 +/- 20.0)
      and nodular fasciitis (33.6 +/- 20.9) exhibited a larger value and a greater
      variation in the PCNA score than did either abdominal (13.5 +/- 14.5) or
      extraabdominal fibromatosis (19.9 +/- 21.5). Abdominal fibromatosis exhibited a
      smaller value and less variation in the score. In short, the PCNA score did not
      correlate with the malignant potential. The proliferative index (S + G2 + M
      fraction) in fibrosarcoma was significantly higher than in either nodular
      fasciitis or abdominal fibromatosis. Aneuploidy was detected in five cases (26%)
      of fibrosarcoma, while six (26%) fibrosarcomas showed p53 positivity.
      Furthermore, p53-positive patients had a worse survival (0.01 < p < 0.05), and
      p53 positivity correlated with the proliferative index (p < 0.01). In conclusion,
      the PCNA score simply indicates the proliferative activity independent of
      malignant potential. On the other hand, p53 positivity, proliferative index, and
      aneuploidy are all indicators of malignant potential in fibroblastic lesions, and
      p53 positivity may reflect a poor prognosis.

PMID- 7517106
TI  - Pharmacokinetics of aprotinin in preoperative cardiac surgical patients.
AB  - BACKGROUND: Aprotinin, a polypeptide protease inhibitor, reduces bleeding and
      transfusion requirements during cardiac surgery. To investigate aprotinin's
      pharmacokinetics, we administered therapeutic doses to patients scheduled to
      undergo cardiac surgery. METHODS: Preoperative doses of 500,000 and 1,000,000
      kallikrein inhibitor units (KIU) were administered as an infusion over 30 min to
      28 patients, and plasma concentrations were measured for 48 h. Aprotinin
      concentrations were determined using a sandwich-enzyme-linked immunosorbent
      assay. A three-compartment model was fit to the measured aprotinin concentrations
      using extended nonlinear least-squares regression. RESULTS: Plasma aprotinin
      concentrations at the end of the 30-min infusion were 147 +/- 61 KIU/ml for the
      1,000,000-KIU dose and 60 +/- 19 KIU/ml for the 500,000-KIU dose. Elimination
      clearance was 35.5 ml/min, and volume of distribution at steady state was 26.5 l.
      CONCLUSIONS: A 2,000,000-KIU dose is needed to produce the plasma concentration
      of 200 KIU/ml associated with kallikrein inhibition. Plasma concentrations in
      excess of 50 KIU/ml, the concentration required to inhibit plasmin, can be
      achieved by a significantly smaller dose. Based on the derived pharmacokinetic
      parameters, an infusion model was developed to appropriately administer and
      maintain effective plasma concentrations of aprotinin, depending on the plasma
      concentration desired and the target proteases to be inhibited.

PMID- 7517103
TI  - Comparison of individual and group/consultation treatment methods for preschool
      children with developmental delays.
AB  - OBJECTIVES: Although alternative treatment methods are becoming more widely
      discussed and implemented in pediatric occupational therapy, empirical data
      demonstrating the effectiveness of these treatment methods are lacking. The
      present study compares the effectiveness of an alternative treatment method
      (group/consultation) to traditional direct therapy. METHOD: Eighteen preschool
      subjects classified as developmentally delayed received either individual/direct
      therapy or group/consultation therapy. Each child was assessed initially and
      again 7 months later with three standardized tests assessing fine motor and gross
      motor development, functional skills in the home, and nonverbal intelligence.
      RESULTS: Subjects in both treatment methods demonstrated significant increases in
      both fine and gross motor skills with the rate approximating that of the normal
      distribution of typically developing children. CONCLUSION: There were no
      statistically significant differences between treatment methods on any of the
      assessments.

PMID- 7517105
TI  - Antibody-mediated fluorescence enhancement based on shifting the intramolecular
      dimer<-->monomer equilibrium of fluorescent dyes.
AB  - A novel concept is described for directly coupling fluorescence emission to
      protein-ligand binding. It is based on shifting the intramolecular monomer<-
      >dimer equilibrium of two fluorescent dyes linked by a short spacer. A 13-residue
      peptide, recognized by a monoclonal antibody against human chorionic
      gonadotrophin (hCG), was labeled with fluorescein (F) and tetramethylrhodamine
      (T) at its N- and C-terminus, respectively. Spectral evidence suggests that when
      the conjugate is free in solution, F and T exist as an intramolecular dimer.
      Fluorescence quenching of fluorescein and rhodamine is approximately 98% and
      approximately 90%, respectively, due to dimerization. When the double-labeled
      peptide is bound to anti-hCG, however, the rhodamine fluorescence increases by up
      to 7.8-fold, depending upon the excitation wavelength. This is attributed to the
      dissociation of intramolecular dimers brought about by conformational changes of
      the conjugate upon binding. Fluorescein fluorescence, on the other hand, was
      still quenched because of excited-state energy transfer and residual ground-state
      interactions. Antibody binding also resulted in a approximately 3.4-fold increase
      in fluorescence anisotropy of the peptide. These changes in intensity and
      anisotropy allow direct measurement of antigen-antibody binding with a
      fluorescence plate reader or a polarization analyzer, without the need for
      separation steps and labeling antibodies. Because recent advances in peptide
      technology have allowed rapid and economical identification of antigen-mimicking
      peptides, the double-labeled peptide approach offers many opportunities for
      developing new diagnostic assays and screening new therapeutic drugs. It also has
      many potential applications to techniques involving recombinant antibodies,
      biosensors, cell sorting, and DNA probes.

PMID- 7517110
TI  - [Heparin induced thrombopenia].

PMID- 7517108
TI  - [Monitoring of hemostasis during liver transplantation: contribution of
      thromboelastography].
AB  - Monitoring of coagulation is mandatory during liver transplantation (LT).
      Standard coagulation tests may be routinely used. However, they give static
      information and may be inadequate in case of severe coagulation defect. Interest
      has been recently focused on thromboelastography (TEG) which could give more
      suitable and rapid information in these cases. Few studies have evaluated the
      clinical interest of TEG compared to conventional tests. This comparison was the
      aim of the present study, performed in 89 patients scheduled for LT. The
      anaesthetic management as well as procedure of transfusion were similar in all
      patients. Before unclamping, 5000 KIU.kg-1 of aprotinin were injected. Routine
      tests and TEG were performed at the beginning and end of both pre-anhepatic and
      anhepatic phases, and 5, 30, 60, and 120 min after the revascularisation of the
      new liver. A phase of hypocoagulability was observed after unclamping. Biological
      signs included an increase in activated thromboplastin time, a reduction of alpha
      angle and maximum amplitude on TEG with a lengthening of its r + k component. A
      strong correlation existed between maximum amplitude and platelets, maximum
      amplitude and fibrinogen, alpha and fibrinogen at each time of the surgical
      procedure. Euglobulin lysis time decreased significantly after clamping, whereas
      fibrin degradation products increased at the same time. However, typical
      fibrinolysis with a clot lysis index (CLI) below 55% was only observed in 15
      patients. Twelve of them had a CLI value reaching 0%, associated with severe
      generalized oozing. Aprotinin (200,000 to 600,000 KIU) corrected these
      abnormalities. These results show that TEG may not be very helpful to determine
      whether platelets or fibrinogen are involved in the phase of hypocoagulability
      detected after unclamping.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517109
TI  - [Anaphylactic shock during the use of high doses of aprotinin in cardiac
      surgery].
AB  - A 77-year-old man was admitted for mitral valve replacement, 46 days after a
      failed conservative mitral surgery where he received high-dose aprotinin. Twenty
      minutes after induction of anaesthesia, 250 UPh E of aprotinin were infused
      intravenously; before the end of this infusion, bronchospasm, systemic
      hypotension and generalized rash were noted. Immediate treatment included
      intravenous adrenaline and methylprednisolone; cardiovascular stability was
      restored after 10 minutes. Immediate histamine liberation was confirmed by the
      analysis of the time course of the clinical events, a previous contact and
      positive skin tests. Aprotinin has the antigenic molecular structure of natural
      proteins. Since 1987, it is used in cardiac surgery to reduce postoperative blood
      loss: to prevent serious allergic reactions to aprotinin, it is necessary, in
      patients known to have had previous aprotinin therapy, to perform skin testing
      with diluted aprotinin before infusion.

PMID- 7517107
TI  - The dose-related effects of nitric oxide synthase inhibition on cerebral blood
      flow during isoflurane and pentobarbital anesthesia.
AB  - BACKGROUND: Recent work in animals suggests that nitric oxide may play a role in
      the cerebral blood flow (CBF) changes produced by anesthetics, particularly the
      vasodilation seen with volatile anesthetics. It is not clear, however, whether
      nitric oxide causes the flow increase or simply plays some constitutive role. To
      distinguish between these possibilities, we studied the dose-related effects of
      nitric oxide synthase inhibition in rabbits with varying baseline CBFs, produced
      by anesthesia with isoflurane, low-dose pentobarbital, or high-dose
      pentobarbital. METHODS: New Zealand White rabbits were anesthetized with 1 MAC
      isoflurane, low-dose pentobarbital (50-mg/kg load, 7.5-mg.kg-1.h-1 infusion), or
      high-dose pentobarbital (50-mg/kg load, 20-mg.kg-1.h-1, deep burst-suppression on
      the electroencephalogram), and prepared for the measurement of CBF using
      radioactive microspheres. The confluence of sinuses was also exposed to permit
      sampling of cerebral venous blood and the determination of cerebral metabolic
      rate for O2 (CMRO2). Normocapnia and normothermia were maintained throughout.
      After baseline measurements, animals were sequentially given a cumulative total
      of 3, 13, and 43 mg/kg intravenous N omega-nitro-L-arginine methyl ester (L
      NAME), an inhibitor of nitric oxide synthase. CBF and CMRO2 were recorded
      approximately 10 min after each dose. RESULTS: L-NAME produced a dose-related
      reduction in CBF in all three anesthetic groups. Statistical examination
      indicated that the dose response curves were parallel. For example, in isoflurane
      anesthetized rabbits, CBF decreased from 77 +/- 19 to 47 +/- 11 ml.100 g-1.min-1
      after the 43 mg/kg L-NAME, whereas in high-dose pentobarbital animals, CBF
      decreased from 42 +/- 15 to 26 +/- 8 ml.100 g-1.min-1 (all values mean +/- SD).
      Decreases in CMRO2 did not quite achieve significance (P = 0.08), and the
      CBF/CMRO2 ratio decreased in all animals, suggesting that the CBF reductions were
      due primarily to direct vasoconstriction. There were no electroencephalographic
      changes. In separate groups of isoflurane-anesthetized rabbits given 3 mg/kg L
      NAME, treatment with 300 mg/kg L-arginine partially reversed the decreases in
      CBF. By contrast, the effects of 43 mg/kg L-NAME were not reversible with 430
      mg/kg L-arginine. CONCLUSIONS: Although L-NAME reduced CBF in all three
      anesthetic conditions, it did not alter the relative differences among them: CBF
      in the presence of isoflurane remained much higher than that seen with the
      barbiturates. This suggests that nitric oxide may not the primary mediator of
      anesthetic CBF effects, but rather acts to influence background vascular tone in
      these anesthetized animals.

PMID- 7517112
TI  - Controversy over sclerotherapy for malignant pleural effusions.

PMID- 7517111
TI  - Identification of subspecies- and serotype 1-specific epitopes on the 80- to 90
      kilodalton protein region of Chlamydia psittaci that may be useful for diagnosis
      of chlamydial induced abortion.
AB  - Genus-, subspecies-, and serotype 1-specific antigens of Chlamydia psittaci were
      characterized by immunoblot analysis, using monoclonal antibodies that recognize
      2 C psittaci strains: AB7 isolated from an ewe that had aborted, and iB1 isolated
      from feces of a healthy ewe. Genus-specific epitopes were detected on
      lipopolysaccharide, on a 47-kd protein, and on a 27- to 30-kd doublet. Subspecies
      specific epitopes were located on a 30-kd protein, and a 80- to 90-kd protein
      region was identified, which bore subspecies- and serotype 1-specific epitopes.
      These 80- to 90-kd proteins were highly reactive with serum from ewes that had
      aborted and could be a useful antigen for diagnosis of chlamydial induced
      abortion of ruminants.

PMID- 7517113
TI  - Controversy over sclerotherapy for malignant pleural effusions.

PMID- 7517114
TI  - Role of selectins in leukocyte adhesion to platelets and endothelium.

PMID- 7517115
TI  - A GP IIIa ligand-induced binding site antibody detects multiple GP IIb-IIIa
      conformations, and its binding is modulated by various ligands.

PMID- 7517116
TI  - Cell size and surface area determined by flow cytometry.

PMID- 7517117
TI  - Platelet activation and inhibition. Novel signal transduction mechanisms.

PMID- 7517118
TI  - Management of inoperable pelvic carcinomas with complex fistulas: a new approach.

PMID- 7517119
TI  - Interferon and the incorporation of 5-fluorouracil into RNA of normal tissues and
      a secondary liver carcinoma in rat.
AB  - The cytotoxicity of 5-fluorouracil (5-FU) has been related to its incorporation
      into RNA and blocking of DNA synthesis. Interferon may enhance the therapeutic
      efficacy of 5-FU in colorectal cancer. In a model of secondary liver cancer in
      the rat, the incorporation of 5-FU into the acid-soluble fraction (ASF), RNA and
      DNA of several normal tissues and the tumor was determined. The liver nucleotide
      profile and NADPH-cytochrome c reductase activity was examined. A therapeutic
      dose of 5-FU was given for 2 h via the hepatic artery and the rats were killed 1
      h later. Half of them were pretreated with the interferon inducer polyinosinic
      polycytidylic acid (poly(I)-poly(C) and interferon. Pretreatment increased the
      nucleotide (NT)/DNA and RNA/DNA ratios, decreased the cellularity and left the
      specific RNA labelling unchanged in the bone marrow. In the liver the
      pretreatment decreased the NT/DNA and RNA/DNA ratios, (F)UTP, and the NADPH
      cytochrome c reductase activity. The 5-FU incorporation into liver DNA decreased.
      No changes were found in the tumor. The pretreated rats decreased in body weight.
      A decreased RNA synthesis in the liver might indicate a decreased 5-FU
      metabolism, explaining the increased 5-FU AUC in the clinic at interferon
      treatment.

PMID- 7517121
TI  - The biological effects of a high molecular weight form of IGF II in a
      pluripotential human teratocarcinoma cell line.
AB  - The human teratoma cell line Tera 2 synthesizes and secretes insulin like growth
      factors into the culture medium. Size fractionation of conditioned medium by
      acidic gel filtration chromatography showed that the medium contains the
      canonical 7 kD IGF II, as well as a large IGF II variant, immunologically
      crossreactive with canonical IGF II. Amino acid analysis of the Tera 2 secreted
      large IGF II variant has shown that it is biochemically distinct from previously
      isolated high molecular weight variants of IGF II. Both species of IGF II support
      cell multiplication of Tera 2 cultures, albeit with different potency. In spite
      of the resulting potential for autocrine growth of Tera 2, we failed to observe
      such a situation. We propose that one reason for this failure to observe such a
      situation. We propose that one reason for this failure is the co-secretion of the
      29 kD IGF binding protein type 1 with IGF II, which we have demonstrated to
      inhibit the biological effects of the growth factor on Tera 2 cells.

PMID- 7517120
TI  - Inhibition of angiogenesis by aurintricarboxylic acid.
AB  - The triphenylmethane derivative, aurintricarboxylic acid (ATA), but not aurin, is
      a potent inhibitor of angiogenesis in the chick chorioallantoic membrane. ATA
      alone showed potent anti-angiogenic activity in a dose-related manner. The
      presence of heparin or bFGF decreased the anti-angiogenic activity of ATA. ATA
      also potentiated the anti-angiogenic activity of the angiostatic steroids,
      cortisol-21-phosphate, 17 alpha-hydroxyprogesterone, tetrahydrocortisol,
      tetrahydrocortexolone and medroxyprogesterone acetate. These results indicate
      that ATA is a potent inhibitor of angiogenesis and potentiates the activity of
      the angiostatic steroids. These novel findings with this negatively charged,
      nonsulfated aromatic compound may be the basis for important new therapeutic
      approaches for the diseases of neovascularization.

PMID- 7517123
TI  - Experimental therapy of relapsing-remitting multiple sclerosis with copolymer-1.

PMID- 7517124
TI  - Prevention strategies for multiple sclerosis.
AB  - The design of effective prevention strategies for multiple sclerosis (MS) is
      hampered by ignorance of the basic pathophysiology of the disease. An
      understanding of specific immune mechanisms, the nature of genetic
      susceptibility, and environmental triggers will permit rational decision making
      from among the many proposed therapeutic directions available. It is reasonable
      to hypothesize that inhibition of central nervous system inflammation will be of
      benefit in MS, regardless of the trigger (autoantigen, exogenous antigen, or
      nonspecific trigger). Emerging concepts are reviewed to provide guideposts for
      the design of rational therapy for MS.

PMID- 7517122
TI  - Plasmid rescue of an oncogenic sequence containing a mouse mammary tumor virus
      gene.
AB  - Plasmid rescue was performed on an oncogenically transformed cell line
      established by transfection of NIH/3T3 cells with normal mouse DNA and plasmids
      containing a murine leukemia virus long terminal repeat, and a selectable marker.
      One of the rescued plasmids contained newly acquired DNA 3,500 basepairs in
      length. This sequence was present in several extra copies in the parental cell
      line. It was also found to be transcribed. NIH/3T3 cells transfected with the
      rescued plasmid proved to be oncogenic in nude mice. The acquired sequence
      appeared to contain (part of) the long terminal repeat of mouse mammary tumor
      virus.

PMID- 7517125
TI  - Pregnancy and multiple sclerosis.

PMID- 7517126
TI  - Animal models.
AB  - Different models of experimental autoimmune encephalomyelitis (EAE) have been
      successfully applied to investigate and manifold aspects of the autoimmune
      pathogenesis of multiple sclerosis. Studies using myelin-specific T-cell lines
      that transfer EAE to naive recipient animals established that only activated
      lymphocytes are able to cross the endothelial blood-brain barrier and cause
      autoimmune disease within the local parenchyma. All encephalitogenic T cells are
      CD4+ Th1-type lymphocytes that recognize autoantigenic peptides in the context of
      MHC class II molecules. In the case of myelin basic protein (MBP) specific EAE in
      the Lewis rat, the T-cell response is directed against one strongly dominant
      peptide epitope. The encephalitogenic T cells preferentially use one particular
      set of T-cell receptor genes. Although MBP is a strong encephalitogen in many
      species, a number of other brain protein are now known to induce EAE. These
      include mainly myelin components (PLP, MAG, and MOG), but also, the astroglial S
      100 beta protein. Encephalitogenic T cells produce only inflammatory changes in
      the central nervous system, without extensive primary demyelination. Destruction
      of myelin and oligodendrocytes in these models requires additional effector
      mechanisms such as auto-antibodies binding to myelin surface antigens such as the
      myelin-oligodendrocyte glycoprotein.

PMID- 7517127
TI  - Cloning and DNA sequencing of bgaA, a gene encoding an endo-beta-1,3-1,4
      glucanase, from an alkalophilic Bacillus strain (N137).
AB  - The gene bgaA encoding an alkaline endo-beta-1,3-1,4-glucanase (lichenase) from
      an alkalophilic Bacillus sp. strain N137, isolated in our laboratory, was cloned
      and expressed from its own promoter in Escherichia coli. The nucleotide sequence
      of a 1,416-bp DNA fragment containing bgaA was determined and revealed an open
      reading frame of 828 nucleotides. The deduced protein sequence consists of 276
      amino acids and has a 31-amino-acid putative signal peptide which is functional
      in E. coli, in which the BgaA protein is located mainly in the periplasmic space.
      The lichenase activity of BgaA is stable between pH 6 and 12, it shows optimal
      activity at a temperature between 60 and 70 degrees C, and it retains 65% of its
      activity after incubation at 70 degrees C for 1 h. This protein is similar to
      some other lichenases from Bacillus species such as B. amyloliquefaciens, B.
      brevis, B. licheniformis, B. macerans, B. polymyxa, and B. subtilis. However, it
      has a lysine-rich region at the carboxy terminus which is not found in any other
      published lichenase sequence and might be implicated in the unusual biochemical
      properties of this enzyme. The location of the mRNA 5' end was determined by
      primer extension and corresponds to nucleotide 235. A typical Bacillus sigma A
      promoter precedes the transcription start site.

PMID- 7517128
TI  - Group-specific 16S rRNA hybridization probes to describe natural communities of
      methanogens.
AB  - Eight oligonucleotides which are complementary to conserved tracts of 16S rRNA
      from phylogenetically defined groups of methanogens were designed and
      characterized for use as hybridization probes for studies in environmental and
      determinative microbiology. The target-group specificity and temperature of
      dissociation for each probe were characterized. In general, the probes were very
      specific for the target methanogens and did not hybridize to the rRNAs of
      nontarget methanogens. Together, the eight probes circumscribe methanogens now
      represented in pure culture (with the exception of members of the family
      Methanothermaceae). Three probes are order specific; two identify members of the
      order Methanobacteriales, and one is specific for the order Methanococcales. The
      fourth probe encompasses three families belonging to the order
      Methanomicrobiales, the third order within the current classification. The fifth
      probe is specific for the remaining family within this order
      (Methanosarcinaceae). Three additional probes encompass different genera within
      the Methanosarcinaceae.

PMID- 7517129
TI  - Quantification of methanogenic groups in anaerobic biological reactors by
      oligonucleotide probe hybridization.
AB  - The microbial community structure of anaerobic biological reactors was evaluated
      by using oligonucleotide probes complementary to conserved tracts of the 16S
      rRNAs of phylogenetically defined groups of methanogens. Phylogenetically defined
      groups of methanogens were quantified and visualized, respectively, by
      hybridization of 32P- and fluorescent-dye-labeled probes to the 16S rRNAs from
      samples taken from laboratory acetate-fed chemostats, laboratory municipal solid
      waste digestors, and full-scale sewage sludge digestors. Methanosarcina species,
      members of the order Methanobacteriales, and Methanosaeta species were the most
      abundant methanogens present in the chemostats, the solid-waste digestors, and
      the sewage sludge digestors, respectively.

PMID- 7517130
TI  - Identification of Bifidobacterium strains by rRNA gene restriction patterns.
AB  - Total DNA from 21 collection or industrial Bifidobacterium strains was cleaved
      with various restriction endonucleases. Following electrophoresis, the fragments
      were subjected to Southern blot hybridization with a heterologous [alpha-32P]dCTP
      labeled rDNA (genes coding for rRNA) 23S gene probe. The ribosomal patterns
      allowed all tested strains to be differentiated and previous classifications to
      be confirmed. The same method was used to characterize DNA from 121
      Bifidobacterium isolates collected from the intestinal flora of five human
      volunteers after the induction of colonic bacterial imbalance by antibiotics and
      absorption of a resistant exogenous Bifidobacterium strain. Hybridizations with
      the ribosomal probe revealed 11 different ribosomal patterns in addition to that
      of the exogenous strain. They permitted the Bifidobacterium populations belonging
      to the dominant colonic flora to be monitored over time. This experiment revealed
      significant and sustained alterations of the endogenous intestinal flora; indeed,
      some strains were eliminated, while others, probably belonging to subdominant
      flora, replaced them. Furthermore, even 2 months after the end of antibiotic
      treatment, the colonic flora remained different from that observed before
      treatment. Finally, our results showed that antibiotherapy did not allow colonic
      colonization by the exogenous strain.

PMID- 7517132
TI  - Inhibitory effects of enrichment media on the Accuprobe test for Listeria
      monocytogenes.
AB  - During an evaluation of the Accuprobe kit for the detection of Listeria
      monocytogenes, some of the enrichment media used were found to interfere with the
      test. Microscopic examination during the lysis step of the test revealed that
      media containing high salt greatly reduced or prevented cell lysis. This
      prevented the probe from binding to the cellular RNA, resulting in false-negative
      results.

PMID- 7517131
TI  - Cultural and phylogenetic analysis of mixed microbial populations found in
      natural and commercial bioleaching environments.
AB  - A range of autotrophic and heterotrophic enrichment cultures were established to
      determine the cultural bacterial diversity present in samples obtained from the
      acidic runoff of a chalcocite overburden heap and from laboratory-scale (1- to 4
      liter) batch and continuous bioreactors which were being used for the commercial
      assessment of the bioleachability of zinc sulfide ore concentrates. Strains
      identified as Thiobacillus ferrooxidans, Thiobacillus thiooxidans,
      "Leptospirillum ferrooxidans," and Acidiphilium cryptum were isolated from both
      the natural site and the batch bioreactor, but only "L. ferrooxidans," a
      moderately thermophilic strain of T. thiooxidans, and a moderately thermophilic
      iron-oxidizing bacterium could be recovered from the continuous bioreactor
      running under steady-state conditions. Sequence analysis of the 16S rRNA genes of
      33 representative strains revealed that all of the strains were closely related
      to strains which have been sequenced previously and also confirmed the
      phylogenetic diversity of bacteria present in bioleaching environments.

PMID- 7517133
TI  - Quality of life in surgically palliated complex congenital heart disease.
AB  - The outcome of surgical palliation was evaluated in 26 children with complex
      cyanotic congenital heart disease. Outcome was examined in terms of ongoing
      symptoms, exercise tolerance, and the ability to participate in normal childhood
      activities. An activity score was calculated and each child performed graded
      treadmill exercise testing. Breathlessness (24 (92%) children), respiratory
      infections (nine (35%) children), and leg cramps (eight 31%) children) were the
      most common physical disorders. Although formal exercise testing showed a clear
      reduction in exercise tolerance compared with age and sex matched controls,
      palliation had allowed 23 (89%) to function with moderate exercise limitation,
      three (11%) having severely limited activity. Parents underestimated the child's
      exercise tolerance in 80% of cases. Sixteen (62%) patients attended school full
      time, eight (31%) attended part time, and two (8%) received only home tuition.
      Palliative surgery can give children with a single functional ventricle a level
      of activity which allows them to take part in most childhood activities.
      Subjective estimates of exercise tolerance are inaccurate in this group of
      children, and formal exercise testing can contribute useful information to
      decision making about further surgical intervention.

PMID- 7517134
TI  - Central nervous system toxicity related to FK506 in patients with Behcet's
      disease.

PMID- 7517136
TI  - Immunohistochemical evidence for the presence of nerve fibres with substance P-
      or calcitonin gene-related peptide-like immunoreactivity in the proliferating
      epithelium in the developing teeth of rats.
AB  - By immunohistochemistry using the avidin-biotin peroxidase complex method, nerve
      fibres with substance P- or calcitonin gene-related peptide (CGRP)-like
      immunoreactivity (IR) were examined in the dental lamina, cells external to the
      reduced ameloblasts and oral epithelium in the developing upper first molars of
      postnatal rats. At birth, very few varicosities with substance P- or CGRP-IR were
      found in the dental lamina over the mesial cusp of the dental germ. In 5-day-old
      rats, nerve fibres with substance P- or CGRP-IR in the dental lamina over the
      mesial cusp gradually increased in number. In 7-day-old rats, over the mesial
      portion of the dental germ, the oral half of the dental lamina began to thicken
      on the buccopalatal side, in which many nerve fibres with substance P- or CGRP-IR
      were observed. A few nerve fibres began to penetrate the cells external to the
      reduced ameloblasts over the middle buccal cusp. In 10-day-old rats, the oral
      epithelium over the mesial cusp gradually thickened, and nerve fibres with
      substance P- or CGRP-IR were found especially in its basal layer. In 13-15-day
      old rats, a great many nerve fibres with substance P- or CGRP-IR were distributed
      all over the fused, thickened dental lamina and cells external to the reduced
      ameloblasts proliferated over the middle and distal cusps. Nerve fibres with
      substance P- or CGRP-IR formed a plexus in the thickened oral epithelium, which
      spread to the mesiopalatal end of the mesial cusp.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7517137
TI  - Immunocytochemical correlation of peptides and tyrosine hydroxylase in nerve
      fibres of the human parotid gland.
AB  - The peptidergic innervation of parenchymal and vascular components in the human
      parotid gland was investigated by double-labelling fluorescence. Peptide
      immunoreactivity in nerve fibres was correlated with the presence of tyrosine
      hydroxylase (TH). By light microscopy, acinar innervation consisted of fibres
      with the combinations neuropeptide Y (NPY)/TH and NPY/vasoactive intestinal
      polypeptide (VIP). Some fibres were solely NPY, TH or VIP immunoreactive. Rarely,
      substance P (SP)/calcitonin gene-related (CGRP)-immunolabelled fibres were
      associated with acini. Intercalated ducts were often approached by NPY/TH- and
      VIP-containing fibres. VIP innervation of excretory ducts was sparse.
      Intralobular and intralobar excretory ducts, in addition to NPY and TH, revealed
      CGRP and CGRP/SP innervation, whereas nerve fibres on interlobar excretory ducts
      very rarely contained NPY and none of the other mediators. Vascular innervation
      consisted of NPY/TH and SP/CGRP fibres; in a few fibres SP was colocalized with
      leu-enkephalin. Large arteries were encircled by some VIP-positive fibres. The
      findings suggest a specific participation of neuropeptides and of peptide
      combinations in the regulation of parotid exocrine function.

PMID- 7517138
TI  - The effect of vinblastine on the incorporation of [3H]-glycine into proteins of
      the periodontal ligament of impeded and unimpeded mouse incisors.
AB  - The effect of vinblastine on the protein metabolism of the periodontal ligament
      of impeded and unimpeded mouse incisors was studied by [3H]-glycine labelling and
      radioautography. The silver-grain concentration was determined in areas adjacent
      to the tooth, areas adjacent to bone and, as an internal control, in the dentine
      matrix. From 1 to 12 h there was no difference between treated and control
      animals; thus the drug did not alter protein biosynthesis. Later, the silver
      grain concentration was significantly higher in areas adjacent to both bone and
      tooth in vinblastine-treated animals, suggesting a longer half-life of the
      labelled proteins. No significant differences between normal or unimpeded
      erupting incisors of both groups were detected. Dentine matrix showed a possibly
      higher re-utilization of the labelled amino acid in vinblastine-treated animals.
      The amount of labelled protein removed by collagenase was similar in both groups,
      while the concentration of grains due to collagenase-resistant proteins was
      significantly higher in treated animals, particularly at 96 h after the injection
      of labelled glycine. The relation between the increased amount of non-collagenous
      proteins in the periodontal ligament and the decrease in the rate of eruption
      caused by vinblastine was not established. However, among these proteins,
      fibronectin and proteoglycans are thought to be important factors in tooth
      eruption.

PMID- 7517139
TI  - The effect of vitamin A on the proliferation of oral epithelium in the rat.
AB  - This study assessed the effect of topical and systemic 13-cis-retinoic acid on
      rat palatal epithelial proliferation with bromodeoxyuridine labelling and silver
      stained nucleolar organizer regions. Sixty male Wistar rats were assigned
      randomly to a control group or treatment groups of topical orabase, RA in
      orabase, 5 times/week or twice weekly systemic doses of 12 mg RA in coconut oil.
      The rats were treated for 1, 2, 4 or 8 weeks and killed 1 h post-injection of 40
      mg/kg BrdUrd. The palatal mucosae were processed, using immunoperoxidase staining
      or silver stain to visualize BrdUrd utilization or AgNORs, respectively. The
      number of BrdUrd positive nuclei/mm overlying epithelium and number and area of
      AgNORs in the basal cells were assessed using image analysis. ANOVA indicated
      there was no significant effect of treatment on LN/mm or the numbers or areas of
      AgNORs. The LN/mm for the 8 w group (29.5) was significantly lower than the other
      groups. RA did not influence rat palatal epithelial proliferation, but across all
      groups increased age was associated with decreased proliferation. It would appear
      that the proliferation of normal oral mucosa may not be subject to altered
      proliferation when treated with therapeutic doses of topical or systemic RA.

PMID- 7517140
TI  - Improvement of impaired brain monoamine metabolism by the cognition-enhancing
      agent nefiracetam after microsphere-induced cerebral embolism in rats.
AB  - Nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide DM-9384,
      CAS 77191-36-7), a pyrrolidone (cyclic GABA) derivative, is a newly developed
      cognition-enhancing (nootropic) agent. In the present study, the effects of
      nefiracetam on cerebral monoamine metabolism in rats after microsphere-induced
      cerebral embolism have been examined. For cerebral embolization, microspheres
      were injected into the left internal carotid artery. Nefiracetam (3, 10 and 30
      mg/kg p.o.) was administered daily to the animals for 13 days from the 9th day
      after the operation. The levels of DA, DOPAC and HVA in the control (embolism
      induced, but untreated) group were significantly decreased compared with those of
      the normal (non-operated) group. In animals treated with nefiracetam (3 mg/kg
      p.o.), these monoamine levels were higher than controls in the cortex and
      hippocampus, whereas they were not significantly changed in the striatum. 5-HT
      contents in the control group significantly decreased from normal levels in the
      cortex and hippocampus, on which nefiracetam at various doses had no effect. The
      levels of 5-HIAA in the control group also decreased, which were, however,
      significantly increased by 3 mg/kg of nefiracetam. The results suggest that
      nefiracetam has improving actions on the dysfunction of the dopaminergic and
      serotonergic systems induced by cerebral embolism.

PMID- 7517141
TI  - Proteinase activity and proteinase inhibitor detection by SDS-PAGE.

PMID- 7517135
TI  - Women's sexual and emotional responses to male- and female-produced erotica.
AB  - Whether erotic films made by women are more arousing for women than erotic films
      made by men was studied. Forty-seven subjects were exposed to both a woman-made,
      female-initiated, and female centered, erotic film excerpt. Photoplethysmographic
      vaginal pulse amplitude was recorded continuously. Self-report ratings of sexual
      arousal and affective reactions were collected after each stimulus presentation.
      Contrary to expectation, genital arousal did not differ between films, although
      genital response to both films was substantial. Subjective experience of sexual
      arousal was significantly higher during the woman-made film. The man-made film
      evoked more feelings of shame, guilt, and aversion. Correlations between
      subjective experience of sexual arousal and photoplethysmographic measures of
      sexual arousal were nonsignificant. The largest contribution to female sexual
      excitement might result from the processing of stimulus-content and stimulus
      meaning and not from peripheral vasocongestive feedback.

PMID- 7517142
TI  - Thrombin inhibition by fetal distal lung epithelium is different in fetal and
      adult plasma.
AB  - Intra-alveolar fibrin deposition is a cardinal feature of neonatal respiratory
      distress syndrome and likely contributes to short-term and long-term morbidity.
      Previous studies have shown that fetal distal lung epithelial cell (FDLE)
      surfaces express procoagulant activity when incubated with adult plasma and may
      therefore provide one mechanism by which fibrin is generated. However, plasma
      concentrations of prothrombin and thrombin inhibitors differ significantly at
      birth and during the first weeks of life compared with adult values. Therefore,
      we measured thrombin-generating capacity and inhibitor complex formation in cord
      and adult plasma incubated in the presence of FDLE. Although starting cord plasma
      concentrations of prothrombin were 43% of adult values, the amount of thrombin
      generated was decreased by only 21%. When cord plasma concentrations of
      prothrombin were selectively increased to adult values, the amount of thrombin
      generated surpassed adult plasma by 89%. The latter observations suggested that
      thrombin inhibition was impaired in cord plasma compared with adult plasma and
      supplementation of cord plasma with antithrombin III (ATIII) as well as
      prothrombin returned thrombin generation to adult levels. However, the percentage
      of thrombin complexed to inhibitors (59%) at the completion of the experiments
      was similar in cord, cord plus prothrombin, cord plus prothrombin plus ATIII, and
      adult plasmas. Although a higher proportion of thrombin was inhibited by alpha 2
      macroglobulin (alpha 2M) in cord plasma and cord plasma plus prothrombin, this
      did not compensate for the decreased amount of thrombin inhibited by ATIII. When
      cord plasma was supplemented with ATIII as well as prothrombin, the proportions
      of thrombin complexed by the different inhibitors were similar to those of adult
      plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517143
TI  - Glucocorticoids do not alter peptidase expression on a human bronchial epithelial
      cell line.
AB  - Respiratory epithelial cell surface neutral endopeptidase 24.11 (NEP-24.11)
      degrades proinflammatory peptides, and it has been suggested that glucocorticoids
      may reduce airway inflammation, in part, by upregulation of NEP-24.11. Despite
      the potential importance of the epithelium as a metabolic barrier, little is
      known regarding what other peptidases may be present on the epithelial cell
      surface. Using an immortalized bronchial epithelial cell line (BEAS-2B), we have
      shown that human epithelial cells express no detectable angiotensin-converting
      enzyme, carboxypeptidase N, or dipeptidyl(amino)peptidase IV, but express
      significant levels of aminopeptidase M (AmM), as well as NEP-24.11. The presence
      of these enzymes was demonstrated via their degradation of biologically active
      peptides and by flow cytometry. Exposure of cells to the glucocorticoid
      budesonide (10(-7) M) for up to 5 days did not markedly alter the expression of
      NEP-24.11 or AmM, as assessed by flow cytometry, nor did glucocorticoid treatment
      modify rates of peptide hydrolysis by NEP-24.11 or AmM. Thus, BEAS-2B cells have
      both AmM and NEP-24.11 on their surface, and expression of these enzymes is not
      altered by glucocorticoids.

PMID- 7517145
TI  - Expression of phenotypic markers during regeneration of rat tracheal epithelium
      following mechanical injury.
AB  - We examined epithelial regeneration in mechanically injured rat trachea using
      phenotypic markers that identify unique differentiated stages of epithelial
      cells. Following a focal denuding wound, the cells from the adjacent nonwounded
      epithelium flattened and migrated into the wounded site during the first 12 h. At
      24 h, these cells dedifferentiated into poorly differentiated (PD) cells that did
      not precisely resemble any of the mature tracheal cells. Proliferation of PD
      cells produced a multilayered epithelium by 48 h. Mitotic activity, measured as
      mitotic rate (MR) following a 6-h colchicine metaphase blockade, was high at 24 h
      (MR 23.4%) and 48 h (MR 24.0%). These PD cells expressed keratin 14 and Griffonia
      simplicifolia I-isolectin B4 (GSI-B4) lectin binding sites, which are specific
      for basal cells in normal epithelium but did not react with secretory or ciliated
      cell markers. At 72 h, MR fell to 1.8% (control MR 0.38%). The wound was covered
      with a pseudostratified epithelium; secretory cell markers were present at the
      apex of differentiating columnar cells, and a few preciliated cells expressing
      ciliated cell markers appeared. Basal cells also became distinctly recognizable
      and expressed keratin 14 and GSI-B4 binding sites. Newly appearing secretory or
      ciliated cells also expressed these markers but lost them gradually as they
      acquired new sets of specific markers. During epithelial regeneration after
      mechanical injury, "dedifferentiation," "proliferation," and "redifferentiation"
      of epithelial cells occurred, and the PD cell was pivotal in this process.

PMID- 7517144
TI  - Ultrastructural localization of variant forms of cystic fibrosis transmembrane
      conductance regulator in human bronchial epithelial of xenografts.
AB  - Cystic fibrosis (CF) is caused by mutations in the gene encoding a cyclic
      adenosine monophosphate (cAMP)-regulated chloride (CI) channel called the CF
      transmembrane conductance regulator (CFTR). Previous in vitro studies have
      indicated that the most common mutation, delta F508 CFTR (a deletion of
      phenylalanine 508), encodes a protein that is trapped in the endoplasmic
      reticulum (ER), leading to loss of cAMP-regulated CI transport at the plasma
      membrane. Another common variant, G551D CFTR (a G-->D missense mutation at
      position 551), is properly transported to the plasma membrane but is unresponsive
      to cAMP. These hypotheses are based primarily on studies in culture cells. We
      have attempted to extend the in vitro experiments by characterizing the molecular
      pathogenesis of the common mutations, delta F508 and G551D, in the context of a
      more relevant setting, the pseudostratified epithelium of a proximal human
      airway. Recombinant adenoviruses were used to transduce normal and variant forms
      of CFTR into surface epithelial cells of human bronchial xenografts grown in
      nu/nu mice. Recombinant forms of CFTR RNA and protein were expressed at levels
      that exceed expression of the endogenous gene. Immunolocalization of CFTR at the
      light and electron microscopic level indicated that products of the wild type and
      G551D alleles are found primarily at the apical plasma membrane of ciliated
      cells, while the delta F508 variant is distributed diffusely throughout the ER.
      Our data support previous observations primarily made in vitro that the G551D
      variant is a dysfunctional channel that is properly processed and that the delta
      F508 variant undergoes biosynthetic arrest at the level of the ER.

PMID- 7517146
TI  - [Neuro-acanthocytosis with associated myopathy. A case report].
AB  - Abnormalities of striated muscle histology in patients with neuroacanthocytosis
      have been previously attributed to chronic denervation. This hypothesis is based
      in the presence of axonal peripheral neuropathy. In this 37-year-old patient
      clinical, biochemical and histologic data revealed a non specific primary
      myopathy. Other important findings were decreased levels of 5-hydroxy
      indoleacetic acid (5-HILA) and homovanillic acid (HVA) in the CSF, cerebellar and
      basal ganglia atrophy seen in MRI and infertility of probable gonadal origin.

PMID- 7517147
TI  - Multiepitope polypeptide of the HIV-1 envelope induces neutralizing monoclonal
      antibodies against V3 loop.
AB  - A gene encoding a multiepitope polypeptide (MEP) has been synthesized. It
      contains the information for (1) an 11-amino acid (aa) epitope from the C1 region
      of gp120 of HIV-1 and (2) 3 epitopes of 15 amino acids each, from the central
      part of the V3 loop of isolates MN, SC, and WMJII. These four segments are linked
      by the short spacer peptide AGGGA. This gene was cloned in a plasmid vector and
      expressed in Escherichia coli as a fusion product with a 62-aa fragment of human
      IL-2. The recombinant protein TAB1 was purified by washed pellet procedures and
      reversed-phase HPLC. TAB1 was recognized in ELISAs by 25 of 27 sera from
      seropositive individuals. Mice were immunized and several hybridomas were
      obtained. Two of them secrete monoclonal antibodies that react with synthetic
      peptides from isolates MN, WMJI, WMJIII, and SC with an affinity constant in the
      range of 10(8) M-1. They also recognized peptides from isolates SF2 and WMJII,
      but at much lower affinity. The results obtained from peptide ELISAs indicate
      that the putative epitope recognized by these MAbs lies within the sequence
      IHIGPGRAFYT. Classic neutralization assays demonstrated that MAb 2C4 neutralizes
      50% of the MN isolate at 0.6 micrograms/ml but fails to neutralize IIIB and SF2
      strains. The presence of antibodies directed against every one of the component
      peptides in the sera of rabbits immunized with TAB1 was also documented.

PMID- 7517148
TI  - Cross-reactivity between autoimmune anti-U1 snRNP antibodies and neutralizing
      epitopes of HIV-1 gp120/41.
AB  - We report extensive amino acid sequence homology between HIV-1 gp120/41, and >
      33% of a U1 RNA-associated splicing protein, 70K. The latter is a target of
      autoimmune anti-RNP antibodies in mixed connective tissue disease (MCTD). The
      homologies, involving dominant epitopes of 70K and neutralizing epitopes of
      gp120/41, are the basis for mutual antibody cross-reactivity. A key finding is
      that the epitope GRAFVTIG in the V3 loop of gp120 (strain IIIB) is homologous to
      the functionally essential U1 RNA-binding site of 70K. ELISA data reveal a mean
      reactivity of anti-RNP antibodies to V3 IIIB that is as high as that of HIV sera.
      V3 MN, containing the framework sequence G-AF-T, also cross-reacts with anti-RNP
      antibodies, as do hydrophilic epitopes in gp41 homologous to the COOH end of 70K.
      Further, there is strong cross-reactivity between HIV sera and 70K in Western
      blots. In contrast, antibodies from a related autoimmune disorder, Sjogren's
      syndrome (SS), are neither V3 nor gp41 selective. We conclude that the
      substantial cross-reactivities reported here are due to conserved, antigenically
      dominant B cell epitopes having homologous counterparts in 70K and gp120/41.
      Because antibody production in both MCTD and HIV-1 infection is T cell dependent,
      the results imply that common T cell clones are also activated in these two
      disease paradigms. Further exploration of the mechanisms that activate these
      clones, and that control their divergent fates in MCTD and AIDS, may provide new
      insights into immune dysregulation in HIV infection.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7517149
TI  - The costs of peripheral blood progenitor cell reinfusion mobilised by granulocyte
      colony-stimulating factor following high dose melphalan as compared with
      conventional therapy in multiple myeloma.
AB  - In a retrospective study, we calculated the treatment costs of 26 patients, who
      received either high dose melphalan combined with granulocyte colony-stimulating
      factor (G-CSF; filgrastim)(n = 7) or without G-CSF (n = 11) or alternatively,
      peripheral blood progenitor cell reinfusion (PBPC) mobilised by G-CSF following
      high dose melphalan. In comparison with the control group, a shortening of the
      pancytopenic period and platelet recovery was noticed in the PBPC group. This
      resulted in a reduction in hospital costs, diagnostics, laboratory services,
      total parenteral nutrition and transfusions. The average costs per treatment in
      the PBPC group amounted to about US$ 17,908 as compared to US$ 32,223 in the
      control group, implying a cost reduction of 44% when changing to PBPC reinfusion.

PMID- 7517151
TI  - Acidic and basic fibroblast growth factors in human breast tissue.
AB  - Previously we have reported changes in fibroblast growth factors (FGF) in
      conditioned medium (CM) derived from rat mammary tumours undergoing remission. We
      have used a similar approach to assay for the presence of FGFs in human breast
      tissue and cell lines. The majority of cancer tissues (35/50), benign tissues
      (8/9) and all cancer adjacent normal tissues (20/20) released heat labile, NR6
      transforming activity which coeluted from heparin with acidic FGF (aFGF) at 0.9
      1.1 M NaCl and was neutralised by antibodies to aFGF. The conclusion that the
      majority of breast cancers contain active aFGF was supported by immunoblotting.
      The CM of a minority (15/50) of cancers and one benign tissue had highly
      transforming activity for NR6 cells, and was mitogenic for a breast cancer cell
      line, was heat labile, and strongly heparin binding, eluting at 1.5-2.0 M salt.
      It was not immunoreactive with antibodies to aFGF, basic FGF (bFGF) or Kaposi's
      FGF (kFGF) and its activity was reduced by the presence of aFGF, suggesting
      competition for the same receptor. Very little aFGF was observed in the CM of
      these tumours, and neither aFGF nor other FGF activity was detected in CM of
      breast cell lines.

PMID- 7517150
TI  - Combination chemotherapy with epirubicin and mitomycin C as first-line treatment
      in advanced breast cancer.
AB  - From December 1988 to February 1991, 112 consecutive patients were submitted to
      epirubicin + mitomycin C chemotherapy as first-line treatment for advanced breast
      cancer. Epirubicin (75 mg/m2) was given every 3 weeks and mitomycin C (10 mg/m2)
      every 6 weeks. Only patients with visceral involvement or with a disease-free
      interval of less than 12 months were considered eligible. 102 patients were
      evaluated for response and toxicity in the present analysis. The main sites of
      involvement were viscera, soft tissues, bone in 71 (69.6%), 19 (18.6%) and 12
      (11.8%) patients, respectively. Multiple site involvement was present in 66
      (64.7%) cases. A total of 726 courses of therapy were administered (range 2-14;
      mean 7.2). Follow-up ranged from 96 to 210 weeks (median follow-up 138 weeks).
      Response rate was complete response (CR): 21.6% [95% confidence interval (CI) +/-
      0.8], partial response (PR) 49.0% (95% CI +/- 0.1), stable disease (SD) 12.7%
      (95% CI +/- 0.1), progressive disease (PD) 16.7% (95% CI +/- 0.1), CR + PR: 70.6%
      (95% CI +/- 0.1). Median values of survival and time to progression were 79.4 and
      42 weeks, respectively. At 2 years, 37.2 +/- 4.7% and 12.8 +/- 3.3% of the
      patients, respectively, were alive or without evidence of progression. Toxicity
      was generally mild. One hundred and four (14.3%) cycles in 53 patients were
      delayed due to haematological (82) or cardiac (3) toxicity, infectious disease
      (11) or causes not related to the treatment (8).

PMID- 7517152
TI  - Taxol in epithelial ovarian cancer.
AB  - Epithelial ovarian cancer is the fifth most common cause of cancer death in
      women. The management of patients with advanced disease involves surgery followed
      by platinum-based chemotherapy, but most patients will have either residual or
      recurrent disease. Salvage therapy in these patients is poor, with response rates
      less than 20%. Taxol, a new antineoplastic agent, was first noted to have
      activity in platinum-resistant ovarian cancer in a phase I study. Since then,
      response rates of 20% to 35% have been noted in several phase II studies
      involving hundreds of patients. Major toxicities include neutropenia and
      peripheral neuropathy. Taxol dose escalation with granulocyte-colony stimulating
      factor support, and Taxol in combination with cisplatin, have been tested and
      shown to be feasible. Intraperitoneal administration of Taxol is possible and
      appears advantageous from a pharmacokinetic perspective. A phase III study of
      Taxol and cisplatin in suboptimal disease was completed, and toxicity data show
      that Taxol administration is safe in a multi-institutional setting. Planned
      clinical development of Taxol includes use in less bulky stage III disease and
      dose escalation in platinum-resistant disease. Taxol has already become a major
      treatment of platinum-resistant disease. Further investigation will determine its
      role in the overall management of ovarian cancer.

PMID- 7517153
TI  - Taxol plus recombinant human granulocyte-colony stimulating factor as initial and
      as salvage chemotherapy for metastatic breast cancer: a preliminary report.
AB  - Twenty-eight patients received Taxol as their first chemotherapy for stage IV
      breast cancer. An additional 51 patients with extensive prior exposure to other
      chemotherapeutic agents received Taxol as salvage therapy. We found significant
      activity for the drug in both situations, as well as a strong clinical suggestion
      of non-cross-resistance with doxorubicin. An excellent response in previously
      irradiated skin was noted in one case. The routine use of recombinant human
      granulocyte-colony stimulating factor seemed to ameliorate some of the dose
      limiting toxicity of neutropenia. Other toxicity was mild to moderate in most
      cases. With further development, Taxol should play a significant role in the
      systemic management of breast cancer.

PMID- 7517154
TI  - Phase I study of Taxol, doxorubicin, plus granulocyte-colony stimulating factor
      in patients with metastatic breast cancer.
AB  - The objective of this phase I trial was to determine the maximal tolerated dose
      (MTD) of Taxol and doxorubicin administered as a simultaneous intravenous
      infusion over 72 hours every 21 days. Granulocyte-colony stimulating factor (G
      CSF) 10 micrograms/kg, was administered on days 4-18 of each cycle. The treated
      population consisted of metastatic breast cancer patients previously untreated
      with chemotherapy for metastatic disease, who had not received doxorubicin in the
      adjuvant setting and who had bidimensionally measurable disease. The MTD was
      determined to be 75 mg/m2 of doxorubicin and 160 mg/m2 of Taxol. The dose
      limiting toxicity of the combination was clinical typhlitis in three of three
      patients. Other significant toxicities included grade 3 diarrhea at the higher
      dose levels and grade 4 neutropenia in all patients. Eighteen patients were
      treated on this initial phase I study. The overall response rate was 62%, with 6%
      complete responses and 56% partial responses. The combination of doxorubicin and
      Taxol by 72-hour continuous infusion with G-CSF is an active regimen in patients
      with metastatic breast cancer.

PMID- 7517156
TI  - An experimental evaluation of an AIDS educational intervention for WIC mothers.
AB  - The purpose of this study is to determine which of two educational approaches
      have the greater effect on the AIDS/human immunodeficiency virus (HIV) knowledge
      and attitudes of women participating in the Women, Infants, and Children (WIC)
      Program. A modified version of the Centers for Disease Control's (CDC) 1989
      Health Risk Survey was administered to 217 women, who were then randomly assigned
      to either a control group receiving the usual written material, a nurse-educated
      group, or a videotape-educated group. The questionnaires were repeated
      immediately after and 2 months after the intervention. Chi square, Kruskall
      Wallis ANOVA, and a repeated measures ANOVA were used for data analysis. Ninety
      five percent of the subjects were black and the mean age was 25.8 years (+/-
      5.9). The control group had significantly lower (p < or = 0.003) AIDS knowledge
      scores at both posttests, with the lowest knowledge level at 2 months. The
      videotape group had a greater (p < or = 0.048) intent to reduce risky behaviors
      at the initial posttest. Tolerance towards AIDS patients was significantly (p <
      or = 0.025) greater in the videotape and nurse groups. Both videotape and nurse
      education programs increased knowledge and influenced attitudes and behavioral
      intent. The more efficient videotape program had similar effects as the nurse
      program, and may be more generalizable to other populations.

PMID- 7517157
TI  - Urinary excretion of microelements in endurance-trained volunteers during
      restriction of muscular activity and chronic rehydration.
AB  - The objective of this investigation was to determine the effect of daily intake
      of fluid and salt supplementation (FSS) on increased urinary losses of
      microelements that developed during hypokinesia (decreased number of walking
      steps/d). The studies were performed on 30 endurance-trained male volunteers aged
      23-26 yr, with an averaged maximum oxygen uptake of 65 mL/kg/min during 364 d of
      hypokinesia (HK). All volunteers were divided into three equal groups: Ten
      volunteers were placed continuously under an average of 10,000 running steps/d
      (14.2 km/d) (control subjects), ten volunteers subjected continuously to HK
      without the use of FSS (hypokinetic subjects), and ten volunteers were
      continuously submitted to HK and consumed daily FSS (hyperhydrated subjects). For
      the simulation of the hypokinetic effect the hypokinetic and hyperhydrated
      volunteers were kept under an average of 3,000 walking steps/d (2.7 km/d) for 364
      d. Prior to their exposure to HK the volunteers were on an average of 10,000
      running steps/d (14.2 km/d). During the prehypokinetic period of 60 d and during
      the hypokinetic period of 364 d were determined renal excretion of microelements
      responses of endurance-trained volunteers. In the hyperhydrated volunteers
      urinary excretion of iron, zinc, copper, manganese, cobalt, nickel, lead, tin,
      chromium, aluminum, molybdenum, and vanadium decreased, whereas in the
      hypokinetic volunteers it increased significantly. It was concluded that chronic
      hyperhydration may be used to attenuate urinary excretion of microelements in
      endurance-trained volunteers during prolonged restriction of muscular activity.

PMID- 7517155
TI  - Reducing AIDS and other STDs among inner-city Hispanics: the use of qualitative
      research in the development of video-based patient education.
AB  - We report on the use of qualitative research in the design of video-based
      interventions aimed at reducing AIDS and other sexually transmitted diseases
      (STDs) among inner-city Hispanics. Focus groups, personal interviews, and clinic
      observations were conducted in the South Bronx and Queens, New York, to inform
      the development of culturally sensitive video-based materials for improving
      prevention education provided at inner-city STD clinics. Findings elucidate
      culturally defined gender roles and responsibilities regarding the introduction
      of condom use into primary and nonprimary relationships, as well as other norms,
      attitudes, and behaviors reducing the effectiveness of current AIDS and other STD
      prevention efforts. Too often, educational materials--including an increasing
      number of videos--are based on untested assumptions about what information should
      be provided rather than adequate formative research. One reason may be that the
      literature contains few accounts of how the empirical evidence obtained through
      such research can be translated into theoretically sound interventions. This
      paper explicates such a process.

PMID- 7517158
TI  - Comparison between total and ultrafiltrable serum zinc as test to diagnose zinc
      deficiency in infants and children.
AB  - Total Serum Zinc (TSZn) and albumin were determined, and low molecular weight
      serum Zn measured by radiochemical UltraFiltration (UFSZn) in healthy Dutch
      infants and children, and in samples obtained from those with diseases that are
      expected to alter TSZn. Our control TSZn values, 10.2 +/- 3.5 mumol/L, were low
      compared to those reported in the literature. Variation in serum albumin could
      not explain this: No correlation of TSZn with serum albumin was found (p > 0.5).
      Likely explanations are the nonfasting state and the stress owing to hospital
      surroundings at the time of sampling. A range of other influences not registered
      may be active and are discussed. No significant age-dependence was found (p <
      0.8). Boys over 9 yr of age showed higher TSZn compared with girls of the same
      age (p < 0.08). In a separate experiment a 17% decrease in TSZn was demonstrated
      by food intake (eggs). These results support the opinion that TSZn is of little
      value to measure Zn status. There was no discrimination in TSZn between healthy
      subjects and patients. Our UFSZn values, 0.28 +/- 0.13 mumol/L in the controls as
      well as in the patients, were correlated with TSZn and therefore not a suitable
      alternative for the measurement of TSZn as parameter to determine the Zn status.
      The UFSZn was not correlated with serum albumin (p < 0.7). UFSZn values were
      higher in infants (p < 0.01), no sex dependence was found. We conclude that TSZn
      as well as UFSZn are of limited clinical relevance.

PMID- 7517159
TI  - Uptake, distribution, and turnover rates of selenium in barley.
AB  - The present communication elucidates initially the topographic distribution of
      selenium in barley grains. Then by the fluorimetric method the uptake of selenium
      (selenite) in 8-16 d old germinating barley was estimated. Finally by means of
      75Se the anabolic and catabolic rates (turnover) of 75Se (selenite) was compared.
      The distribution of selenium in barley was evaluated after micro-dissection of
      barley grains. In dried grains the highest concentration was found in husk and
      pericarp with about 0.6 ppm Se. Then followed Scutellum with 0.4 and 0.3 ppm in
      embryon. The aleurone layer, embryonic leaves, and initial root did only have 0.2
      ppm Se. In order to know more about the uptake and distribution of selenium in 8
      d-old barley, the plants were cultivated for a further 8 d in the culture medium
      with variation in selenite concentration. In roots and leaves, the uptake did not
      arrive at saturation during the period studied since the dose-response curve
      increased up to 0.34 mM selenite in the medium, whereas the selenium levels were
      about 200 ppm in roots and 30 ppm in leaves. However, the uptake was linear, with
      concentration during 8 d of cultivation up to 0.84 microM selenite for grain and
      stem. At higher concentrations the dose-response curve diminished its slope. At
      0.34 mM selenite the concentration in grain increased to 6.87 ppm and in the stem
      to 8.13 ppm. The uptake, distribution, and catabolic rate of selenium components
      in germinating barley were further evaluated by exposing the plants to 0.0492
      microCi 75Se (12.6 microM selenite) for up to 4 d. Then the plants were moved to
      a selenium deficient medium for further 4 d. Then finally the medium was
      supplemented with high doses of cold selenite (0.126 mM selenite) for further 4
      d. The first third period made it possible to estimate the rate of uptake. It was
      highest in roots (313 fmol/h/mg dw), i.e., about 10 times those of grains, stems,
      and leaves. The intermediate period where the barley was transferred to a
      selenium deficient medium made it possible to estimate the kinetics and eventual
      sparing mechanisms. The selenium losses were highest for leaves (39%), then
      followed by roots and stems (22 and 25%, respectively). The losses were lowest in
      grain with 9% Se losses. The losses were three times more pronounced during the
      first day than in the following 3 d. These data may argue that the selenium is
      distributed into different pools and that sparing mechanisms may be in
      function.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7517160
TI  - Serum copper and zinc in industrial centers in Slovakia.
AB  - The association between serum copper and zinc concentrations and age, sex, and
      other risk factors of cardiovascular disease in randomly selected adult
      volunteers aged 19-59 were investigated. There was a positive relationship
      between copper and age in both sexes, but zinc was negatively correlated with age
      in males only. Serum zinc was positively related to HDL-cholesterol in males.
      Serum copper was positively related to total cholesterol and LDL-cholesterol but
      negatively correlated to HDL-cholesterol in males. A positive relationship to
      body mass index was observed in females only. Subjects have been divided into a
      control group and a group with marked risk factors of cardiovascular disease. The
      levels of zinc were not different, whereas the levels of copper in both males and
      females were significantly higher in the risk group. Our results suggested a
      positive relationship between serum copper and cumulation of more factors of
      cardiovascular disease, however, their causal effect in human has to be
      investigated further.

PMID- 7517162
TI  - Sodium selenite therapy and thyroid-hormone status in cystic fibrosis and
      congenital hypothyroidism.
AB  - The effectiveness of a peroral sodium selenite therapy (115 micrograms Se/m2
      BSA/d) administered to cystic fibrosis patients (n = 32) could after three months
      be identified in a significant serum selenium increase (0.69-->0.96 mumol/L), a
      significant malondialdehyde decrease (2.72-->1.64 mumol/L), as well as in a
      significant serum vitamin E increase (4.31-->5.72 micrograms/mL). Parallel to
      that, a serum T3 increase as well as a highly significant decrease in the serum
      T4/T3-ratio were found, too, which point to improved peripheral T4-->T3
      conversion during selenium medication. Type-I-iodothyronine-5'-deiodinase has
      recently been identified as a specific selenoenzyme. In the case of congenital
      hypothyroidism (n = 37) application of sodium selenite in the above specified
      dosage yielded a mean serum selenium increase (0.87-->1.12 mumol/L), a not
      significant T3 increase (2.57-->2.61 nmol/L) as well as a not significant TSH
      decrease (5.34-->4.49 mIU/L) without an expected T4 decrease. With the serum
      lipids, however, a lowering of total cholesterol (4.85-->4.53 mmol/L)
      simultaneous with a mean increase in HDL-cholesterol (1.52-->1.66 mmol/L) as well
      as a decrease in LDL-cholesterol (2.93-->2.52) could be observed. We view the
      reduction of the atherogenic serum lipid constellation in the course of selenium
      medication as an expression of increased thyroid-hormone efficacy. Apart from an
      improvement of the antioxidant status a stimulation of thyroid-hormone efficacy
      owing to increased T4--T3 conversion is also noteworthy in sodium selenite
      medication.

PMID- 7517161
TI  - Thyroid function and deiodinase activities in rats with marginal iodine
      deficiency.
AB  - The hypothesis tested was whether marginal iodine deficiency for a period of 6 wk
      affects iodothyronine deiodinase activities in liver and brain of rats. Male rats
      were fed purified diets either deficient or sufficient in iodine; the diets were
      fed on a restricted basis (60% of ad libitum intake). Body weight gain of the two
      groups was comparable. Iodine deficiency was evidenced by increased thyroid
      weight (26%), reduced urinary iodine excretion (80%), and reduced plasma T4
      concentrations (22%). Activities of liver type I and brain type III deiodinase
      were unchanged, but the activity of type II deiodinase in brain was increased
      (28%) in the iodine-deficient rats. Food restriction per se significantly lowered
      T3 (30%) and T4 (22%) concentrations in plasma and decreased type III deiodinase
      activity in brain (30%). These results indicate that in marginal iodine
      deficiency the activities of hepatic type I deiodinase and brain type III
      deiodinase are unchanged, whereas that of brain type II deiodinase is increased.

PMID- 7517163
TI  - Mercury and selenium distribution in human kidney cortex.
AB  - Concentration of mercury and selenium were analyzed in tissue fractions of human
      kidney cortex samples from seven autopsy cases. Total mercury content ranged
      between 0.3-9.0 nmol Hg/g wet wt. Between 27-61% of the total mercury was found
      in the 105,000g supernatant of the tissue homogenate from six cases. In kidney
      cortex from the seventh case, a decreased dentist with the highest concentration
      of mercury, only 3% of the total mercury was found in the 105,000g supernatant
      and about 88% in a SDS-insoluble fraction. In this fraction the molar ratio
      between mercury and selenium was close to 1:1. This study supports results from
      previous animal studies and indicates that mercury in human kidney cortex could
      be deposited in forms with different solubility. It could be of importance to
      speciate different forms of mercury in tissues according to solubility and
      association to selenium when interpretations of mercury concentrations are made.

PMID- 7517164
TI  - Changes in drinking water selenium and mortality for coronary disease in a
      residential cohort.
AB  - In a part of the municipal territory of Reggio Emilia, northern Italy, selenium
      in drinking water decreased from 7 micrograms/L to less than 1 micrograms/L. In a
      cohort of 4419 individuals, previously exposed for at least 5 yr to the drinking
      water with higher selenium content, the 7-yr temporal distribution of deaths for
      coronary disease and for stroke was analyzed to examine a possible relationship
      with changes in drinking water selenium. From January 1986 until August 1988,
      when tap water selenium was 7 micrograms/L, deaths for coronary disease were one
      in males and two in females. After the decrease in drinking water selenium, 21
      and 10 coronary deaths were observed, respectively, in males and in females from
      September 1988 to December 1992. No significant difference in the temporal
      distribution of stroke deaths was observed both in males and in females. Even if
      an effect of chance and aging in the temporal distribution of coronary deaths may
      not be excluded, findings of the study seem to be consistent with the hypothesis
      of a beneficial effect of selenium on coronary disease mortality.

PMID- 7517166
TI  - Biokinetics of iodine-131 in rat thyroid following lead and lithium
      supplementation.
AB  - The impact of lead as an environmental pollutant on the I-131 uptake and
      retention in rat thyroid was assayed alone and in combination with lithium
      treatment. Lead treatment significantly stimulated the 2- and 24-h uptake of I
      131 in the thyroid, and the 24-h uptake showed the maximum stimulation after 3 mo
      of lead treatment. On the contrary, lithium supplementation reduced the uptake
      significantly and the maximum decrease was noticed after 2 mo of lithium
      administration. Further, simultaneous lead and lithium treatment resulted in more
      pronounced increase in the uptake of I-131 by the thyroid, which was maximum
      after 3 mo of combined treatment. The thyroid biological half-life of I-131
      (Tbiol) was found to be increased significantly following lead and lithium
      treatments when given separately. Interestingly, combined lead and lithium
      treatment given up to 2 mo further prolonged the Tbiol of I-131, thus reflecting
      its increased retention.

PMID- 7517165
TI  - Factors affecting the selenium intake of people in Transbaikalian Russia.
AB  - The selenium concentration in foods grown and consumed and in plasma, red blood
      cells, and toenails of people living in the district of Chita in the
      transbaikalian part of Russia were studied in August 1991. Preliminary results
      from the area have suggested low selenium intakes and the possible occurrence of
      cardiomyopathy (Keshan disease) in the population. A low selenium concentration
      in foods grown locally was found: mean selenium concentration in wheat grains was
      1, 5, and 28 micrograms/kg, respectively, in three villages studied, that of oats
      was between 3-6 micrograms/kg, and of cow's milk 10-27 micrograms/kg dry matter.
      The selenium concentration of bread was considerably higher, between 87-337
      micrograms/kg dry wt, presumably because wheat imported from the US had been used
      for baking. Occasional samples of pork, beef, and mutton contained between 32-218
      micrograms selenium/kg dry wt. Low selenium concentrations were observed in
      samples of soil and river water. The mean plasma selenium concentration of 52
      persons was 1.02 mumol/L, including 33 children and 19 adult subjects. The
      selenium concentrations in red blood cells and toenails were 1.95 mumol/L and
      0.61 mg/kg, respectively. No symptoms of heart disease caused by selenium
      deficiency were observed. It is concluded that the selenium status of people was
      fairly good thanks to the contribution to dietary intake of imported wheat with a
      high selenium content. As the selenium concentration was very low in foods grown
      in the area, the selenium intake of the population will be reduced to a very low
      level if only locally produced foods are consumed.

PMID- 7517167
TI  - Metallothionein and zinc homeostasis during tumor progression. Effect of
      methotrexate treatment.
AB  - Zinc homeostasis was studied during the induction, growth, and methotrexate (MTX)
      treatment of Dark Agouti rat mammary adenocarcinomas (DAMA). A progressive fall
      in plasma Zn concentration (pZn), significant at a tumor burden of less than 1%
      body weight (bw), was sustained during tumor enlargement to give a 54% reduction
      in pZn at 16.3% bw (n = 6/group). The hypozincemia was attributed to the
      increasing Zn demand for tumor growth. Zn content of the 16.3% bw tumors equaled
      that of muscle (normally 60% of total body Zn). Tumor metallothionein (tMT) was
      sufficient to bind < 3% of total tumor Zn, and hepatic MT (hMT) remained at basal
      concentrations during early tumor growth, doubling only in the presence of
      significant necrosis in large tumors. Methotrexate (MTX, 0.5 mg/Kg im x 2 d) at
      respective tumor burdens of 5 and 10% bw (n = 9, 10/group) gave 2 therapeutic
      effects, dependent on tumor size: 1.5% bw tumors in 7 rats remained close to
      their original size until experiment end when pZn, hMT, and tMT were typical of
      5% bw untreated tumors. 2. Tumors in 5 rats given MTX at 10% bw had marked
      subcapsular necrosis and regression to a size similar to those in group 1; pZn
      returned toward normal, whereas hMT was 6 times its 5% bw counterpart. Host
      weight loss was significantly reduced, as were tumor-associated changes in plasma
      glucose and calcium. In summary, neither tMT nor hMT appears to play a role in
      the hypozincemia that follows DAMA Zn sequestration and growth. Critically timed
      MTX can result in tumor regression and return of plasma Zn, Ca, and glucose
      toward normal. This is associated with an increase in hMT and reduction in host
      weight loss, suggesting a flow of Zn from the resorbing tumor to the host,
      enabling the synthesis of hMT and retention of host structural proteins.

PMID- 7517168
TI  - Immunogenicity of recombinant human interleukin-2: biological features and
      clinical relevance.
AB  - The immunogenicity of recombinant interleukin-2 (rIL-2, EuroCetus, Amsterdam,
      Netherlands) was studied in seventy-six patients receiving different subcutaneous
      immunotherapy regimens. Patients presented with progressive metastatic renal cell
      carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's
      disease. An enzyme immunoassay (EIA) was employed to screen patients for
      development of non-neutralizing antibodies against rIL-2, antibody specificity
      was confirmed by a standard Western blot. Neutralizing serum activity against rIL
      2 was detected using a standard CTLL mouse proliferation assay. Additionally,
      serum levels of soluble interleukin-2 receptors and lymphocyte subsets expressing
      the CD56 natural killer (NK) associated antigen were measured. In a proportion of
      approximately 35% to 90% of the patients treated, non-neutralizing antibodies
      against rIL-2 could be detected after all treatment courses were evaluated.
      Antibodies were of the IgG, IgM, IgA and IgD subtypes. None of the 76 patients
      exhibited serum neutralizing activity after one treatment course. Five patients
      exhibited neutralizing anti-rIL-2 serum activity after two or more treatment
      courses of systemic rIL-2. In three of these patients, antibodies neutralized
      both recombinant and natural IL-2. Patients developing neutralizing anti-rIL-2
      antibodies, exhibited significantly lower serum sIL-2 receptor levels upon the
      emergence of serum neutralizing activity than patients without antibody.
      Additionally, NK cell associated CD56 positivity was significantly lower in
      patients who exhibited neutralizing anti-rIL-2 serum activity than in patients
      who did not. A significant decrease in levels of soluble IL-2 receptors and CD56
      NK cell positivity was observed, when comparing values prior to and after onset
      of serum neutralizing activity against rIL-2. However, while emergence of
      neutralizing antibodies to rIL-2 diminished rIL-2 induced biological activation,
      it did not coincide with abrogation of treatment response.

PMID- 7517169
TI  - Phase II trial of megestrol in the supportive care of patients receiving dose
      intensive chemotherapy.
AB  - Megestrol acetate was given daily to lung cancer patients undergoing therapy with
      CODE and to recurrent head and neck cancer patients receiving DEB/M in an attempt
      to prevent weight loss. The outcomes in this study were compared with the same
      outcomes in similar groups of patients treated with the same chemotherapy
      regimens, but in which prednisone was used as the main supportive drug along with
      co-trimoxazole, ketoconazole, and either cimetidine or sucralfate. Weight loss
      was less pronounced in the current patients than in the previous ones.
      Nevertheless, there were several factors that led us to conclude that megestrol
      is not an adequate substitute for prednisone in patients receiving this kind of
      chemotherapy.

PMID- 7517170
TI  - Toxicity of ifosfamide, cyclophosphamide and their metabolites in renal tubular
      cells in culture.
AB  - Ifosfamide (IF) and cyclophosphamide (CP) are highly effective alkylating
      cytostatic drugs. IF and CP have to be activated through a metabolic step in
      vivo; numerous metabolites are known. While both IF and its structural isomer CP
      have severe urotoxic side effects, only IF is also a nephrotoxic drug, causing
      tubular damage resulting in Fanconi syndrome in some cases. Little information is
      available regarding the pathogenic mechanism of tubular damage by IF. We used the
      renal epithelial cell line LLC-PK1, which has many properties of the proximal
      tubule, in order to investigate the toxicity of IF and CP and of their reactive
      metabolites 4-hydroxy-IF (4-OH-IF), 4-hydroxy-CP (4-OH-CP), acrolein and
      chloroacetaldehyde (CAA). Protein content of monolayers, DNA and RNA synthesis
      were determined by standard techniques (thymidine and uridine incorporation). IF
      and CP had the lowest toxicities of all compounds tested. Both drugs inhibited
      thymidine incorporation by about 30% at a concentration of 300 mumol/l after 1 h
      incubation. 4-OH-IF and 4-OH-CP were significantly more toxic than the parent
      drugs. Thymidine incorporation, the most sensitive parameter, was reduced by
      about 70% by 300 mumol/l of either compound. In addition, 4-OH-CP reduced the
      total protein content of monolayers. 4-OH-IF did not effect protein content and
      RNA synthesis. Acrolein, the most toxic metabolite tested, reduced all three
      parameters significantly at concentrations of 50-75 mumol/l after 1 h.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7517171
TI  - Comparison of FK-506 and cyclosporine regimens in pediatric renal
      transplantation.
AB  - Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were
      evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and
      discontinuation of prednisone was employed only in children receiving FK-506 who
      experienced minor or no rejection episodes during the 1st posttransplant month.
      At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts
      were receiving no prednisone (n = 13) or a mean dosage of 0.07 mg/kg per day (n =
      4). During the 1st month, acute cellular rejection was more common in the FK-506
      group (0.58 vs. 0.21 rejections per patient, P < 0.05) but allograft survival
      (92%) and renal function at 1 year posttransplant were identical in both groups.
      Compared with the cyclosporine regimen, FK-506 immunosuppression may be
      associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr
      virus-induced lymphoproliferative disease. However, the FK-506 group had less
      hirsutism and gingival hypertrophy and required fewer antihypertensive
      medications independent of steroid use. Height standard deviation scores and
      weight-for-height index improved only in pre-adolescents receiving FK-506 but no
      prednisone (P < 0.02 and P < 0.05, respectively), but did not differ between
      children on FK-506 plus prednisone and those in the cyclosporine group. We
      conclude that the major advantages of FK-506 over cyclosporine immunosuppression
      are a reduced severity of hypertension and an improved cosmetic appearance which
      may improve long-term medical compliance. When used as monotherapy, FK-506 also
      shows promise in relieving the growth retardation associated with cyclosporine
      regimens that include prednisone.

PMID- 7517174
TI  - Control of sensitivity to induction of apoptosis in myeloid leukemic cells by
      differentiation and bcl-2 dependent and independent pathways.
AB  - Induction of differentiation in M1 myeloid leukemic cells by the hematopoietic
      cytokines interleukin 6 and granulocyte-colony stimulating factor, or by the
      glucocorticoid dexamethasone, was associated with down-regulation of the
      apoptosis inhibiting gene bcl-2. The cytokine treated leukemic cells showed an
      increased sensitivity to induction of apoptotic cell death by the cancer
      chemotherapy compounds Adriamycin and cytosine arabinoside and by heat shock and
      cycloheximide. Dibutyryl cyclic AMP neither induced differentiation nor down
      regulated bcl-2 expression, but it sensitized the cells to induction of apoptosis
      by some of these agents. Although dexamethasone induced differentiation and down
      regulated bcl-2 expression, it did not sensitize the cells to induction of
      apoptosis and inhibited the apoptosis sensitizing effect of the cytokines and
      dibutyryl cyclic AMP. Dexamethasone did not inhibit induction of apoptosis by
      wild-type p53 or viability factor withdrawal. The apoptosis sensitizing effect of
      the cytokines and dibutyryl cyclic AMP was reversible upon their
      withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517175
TI  - CSF concentrations of neurotensin in schizophrenia: an investigation of clinical
      and biochemical correlates.
AB  - Neurotensin (NT), a peptide which colocalizes with dopamine in some midbrain and
      hypothalamic neurons, has been speculated to play a role in schizophrenic illness
      and in the action of antipsychotic drugs. Previous work suggested a bimodal
      distribution of NT in patients with schizophrenia, with a subgroup having low
      drug-free NT concentrations which normalize with neuroleptic treatment. We
      studied 15 schizophrenic patients with CSF samples collected both off and on
      neuroleptic medication, 12 with only drug-free (DF) samples, and 10 controls.
      There was no significant difference in CSF NT concentrations between patients and
      controls, or between patients off and on medication. However, 7 patients with
      DFNT CSF concentrations below the patient mean showed an increase with
      neuroleptic treatment. Moreover, NT was significantly lower for women.
      Significant correlations with NT concentrations in CSF were found with deficit
      symptoms in patients, and with the age of the CSF sample for all subjects. There
      was no correlation between CSF NT concentrations and patient age, duration of
      illness, or levels of amine metabolites (MHPG, 5HIAA, HVA).

PMID- 7517173
TI  - Prediction of accumulation of 131I-labelled meta-iodobenzylguanidine in
      neuroblastoma cell lines by means of reverse transcription and polymerase chain
      reaction.
AB  - Radiolabelled meta-iodobenzylguanidine (mIBG) currently provides one of the most
      promising options for targeted radiotherapy of neuroblastoma. No means currently
      exists for prediction of mIBG uptake in tumour cells of individual patients other
      than semiquantitative inferences from diagnostic scanning which depend on the
      continued existence of a macroscopic tumour mass. A biological rapid assay which
      could be applied at initial biopsy would be invaluable in selecting patients for
      therapeutic strategies which incorporate radiolabelled mIBG. We have assessed the
      expression of the noradrenaline transporter gene in six human neuroblastoma cell
      lines and in three non-neural crest-derived cell lines using reverse
      transcription followed by the polymerase chain reaction. Transcription of this
      gene was observed in five out of six neuroblastoma cell lines but in none of the
      control cells. A highly significant correlation was established (P < 0.01)
      between gene expression and active cellular accumulation of mIBG. It is suggested
      that semiquantitative evaluation of noradrenaline transporter gene transcripts
      may be predictive of mIBG uptake by tumours in vivo.

PMID- 7517172
TI  - Aggressive lymphomas with renal involvement: a study of 48 patients treated with
      the LNH-84 and LNH-87 regimens. Groupe d'Etude des Lymphomes de l'Adulte.
AB  - In order to describe renal involvement in aggressive non-Hodgkin's lymphomas
      (NHLs) and its prognostic significance, we reviewed the outcome of 48 patients
      with renal involvement treated with the LNH-84 or LNH-87 regimen. Histology was
      diffuse large cell in 29 (60%) patients; immunoblastic, diffuse mixed cell and
      lymphoblastic in four each; follicular large cell, diffuse small cleaved cell and
      diffuse small non-cleaved cell in one each; and unclassified in four. Ann Arbor
      stage was IV in 44 patients, and IE or IIE in four. Tumour mass > or = 10 cm,
      performance status (ECOG scale) > 2 and increased LDH level were present in 69%,
      20% and 76% of patients respectively. Fifteen patients (31%) had multiple
      intraparenchymal nodules, 14 (29%) had direct spread into the kidney from a
      perirenal mass, ten (21%) had a single intraparenchymal nodule and nine (19%) had
      diffuse infiltration. Twenty-one patients (43%) presented with bilateral lesions.
      Three patients (6%) presented with acute renal failure. Ten other patients (21%)
      had serum creatinine > 120 mumol l-1. In 12 of these 13 patients renal function
      was restored with chemotherapy. Twenty-eight patients (57%) achieved complete
      remission. Estimated 4 year disease-free survival was 39%. Disease-free survival
      and actuarial survival at 4 years were estimated to be 58% respectively. Two
      renal parameters had adverse prognostic significance for survival: renal hilum
      involvement (P = 0.02) and diffuse renal infiltration (P = 0.01). A Cox model
      identified only two independent prognostic factors for survival, namely
      performance status > or = 2 and tumour size > or = 10 cm. We conclude that
      alteration in renal function occurs in 27% of patients with renal involvement.
      Systemic chemotherapy improves renal function rapidly. Long-term outcome is
      similar to that expected in NHL patients presenting with the same prognostic
      factors.

PMID- 7517176
TI  - Proliferation and apoptosis of B220+CD4-CD8-TCR alpha beta intermediate T cells
      in the liver of normal adult mice: implication for lpr pathogenesis.
AB  - Small numbers of T cells have been isolated from the normal mouse liver and many
      of these are of the CD4-CD8-TCR alpha beta+ phenotype. Larger numbers of such
      cells are present in the livers of mice homozygous for the lpr mutation and the
      liver has been proposed to be the site of an extrathymic T cell development
      pathway that is expanded in lpr/lpr mice. Using a modified separation procedure
      that increases the liver T cell yield, we have been able to characterize a subset
      of CD4-CD8-TCR alpha beta intermediate T cells that express the B220 epitope of
      the CD45 molecule, and resemble in this and many other ways the accumulating T
      cells in lpr lymph nodes. These cells are an actively dividing population and
      even in healthy, unmanipulated mice a large proportion of them are undergoing
      apoptosis. We propose the model that the normal liver is a major site for T cell
      destruction and that the lpr defect results in failure of this process with
      leakage of B220+CD4-CD8-TCR alpha beta+ cells from the liver to peripheral
      lymphoid tissues, particularly lymph nodes.

PMID- 7517177
TI  - Differential rat T cell recognition of cathepsin D-released fragments of
      mycobacterial 65 kDa heat-shock protein after immunization with either the
      recombinant protein or whole mycobacteria.
AB  - T cells specific for the mycobacterial 65 kDa heat-shock protein (hsp65) play a
      pivotal role in the development of adjuvant arthritis (AA) in Lewis rats. Upon
      adoptive transfer, CD4+ T cells recognizing a particular hsp65 epitope trigger
      the onset of disease. Activation of hsp65-reactive T cells can be achieved by
      immunization with heat-killed mycobacteria in mineral oil--complete Freund's
      adjuvant (CFA)--or with purified recombinant hsp65. Arthritis, however, will only
      develop after immunization with CFA. In fact, preimmunization with hsp65 protects
      against any subsequent attempt to induce AA. In this study, we examined
      polyclonal lymph node cell responses in Lewis rats, immunized with either CFA or
      purified recombinant hsp65 in incomplete Freund's adjuvant, to a set of hsp65
      fragments generated by a mild digestion with cathepsin D. Proliferative responses
      to several hsp65 fragments varied with the type of antigen used for immunization.
      A cathepsin D-released fragment, identified as residues 376-408, preferentially
      triggered proliferation of rat T cells after hsp65 immunization. Preimmunization
      of Lewis rats with this peptide delayed the onset and reduced the severity of AA.
      Preimmunization with another fragment which was preferentially recognized after
      CFA immunization, representing residues 40-60, did not have such a protective
      effect. Our findings suggest the presence of mycobacterial hsp65 determinants
      that selectively trigger AA-regulating T cells and illustrate that cathepsin D
      may be used as an experimental tool to generate such determinants.

PMID- 7517178
TI  - Endoplasmic reticulum signal sequence facilitated transport of peptide epitopes
      restores immunogenicity of an antigen processing defective tumour cell line.
AB  - The identification of MHC-restricted and tumour-specific cytotoxic T lymphocytes
      (CTLs) provides strong evidence in support of T cell-mediated immune surveillance
      against human tumour cells. These CTLs recognize short peptides derived from
      tumour-associated antigens in conjunction with class I molecules expressed on
      tumour cells. In contrast to these observations there are now numerous examples
      to suggest that a number of tumours escape this CTL-mediated control either by
      down-regulating accessory molecules or by blocking the intracellular processing
      of tumour-specific antigens. Recently a number of tumour cell lines have been
      identified which display a transcriptional deficiency of transporters associated
      with antigen processing (also referred to as TAP). The Epstein-Barr virus (EBV)
      associated tumour, Burkitt's lymphoma (BL), is a classic example in this
      category. In the present study we have restored class I-restricted antigen
      processing in a BL cell line by transfecting a minigene expression vector
      encoding a CTL epitope derived from EBV linked to an endoplasmic reticulum
      translocation signal sequence. These minigene transfected BL cells were not only
      susceptible to lysis by virus-specific CTL but were also capable of efficiently
      activating an antigen-specific CTL response. Interestingly, the immunogenicity of
      these BL cells was not affected by the significantly down-regulated expression of
      adhesion molecules such as LFA1 alpha, LFA1 beta and LFA3. These findings suggest
      that resistance of tumour cells to CTL-mediated immune control can be reversed if
      the relevant peptide epitopes are appropriately presented on the cell surface.

PMID- 7517179
TI  - A novel ligand for CD44 is sulfated proteoglycan.
AB  - We report herein identification of a novel ligand for CD44, a cell surface
      glycoprotein implicated in tumor metastasis, lymphocyte differentiation and
      homing. A mouse T cell line CTLL-2 transfected with cDNA encoding a hemopoietic
      form of mouse CD44 exhibited a new self-adhesive phenotype, forming large
      aggregates. The aggregation was blocked by anti-CD44 mAb but little affected by
      hyaluronidase, indicating the involvement of CD44 and its non-hyaluronate ligand
      in the cell aggregation. The ability to induce CD44-dependent aggregation was
      observed in culture supernatants of CTLL-2 and its CD44 transfectants.
      Immunoprecipitation analysis using a CD44-Ig chimeric molecule indicated that
      CTLL-2 and its transfectants synthesized a macromolecule (gp600) which bound
      specifically to CD44. gp600 was readily labeled with radioactive sulfate and
      treatment of gp600 with chondroitinase ABC or AC II generated a lower molecular
      weight species (18-22 kDa), suggesting that gp600 consists of a small core
      protein heavily modified with chondroitin sulfate glycosaminoglycan side chains.
      However, when binding of CD44 was tested in vitro to chondroitinase-sensitive
      purified glycosaminoglycans, such as chondroitin-4-sulfate, chondroitin-6-sulfate
      and dermatan sulfate, no binding was demonstrable, suggesting either that a novel
      type of chondroitinase-sensitive glycosaminoglycan is recognized by CD44 or that
      association of the glycosaminoglycan with a core protein is required for
      recognition by CD44.

PMID- 7517181
TI  - Low dose aspirin in women with raised maternal serum alpha-fetoprotein and
      abnormal Doppler waveform patterns from the uteroplacental circulation.
AB  - OBJECTIVE: To investigate the use of low dose aspirin in the reduction of
      perinatal morbidity and mortality in women with unexplained raised maternal serum
      alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns. DESIGN:
      Prospective randomised controlled trial. SETTING: A tertiary referral obstetric
      service. SUBJECTS: One hundred and sixty-four women referred to our unit with
      raised maternal serum alpha-fetoprotein and a structurally normal fetus had
      abnormal uteroplacental Doppler waveform patterns at 24 weeks of gestation.
      INTERVENTION: Women were randomly allocated to two groups, receiving either low
      dose aspirin 75 mg (n = 76) or placebo (n = 88) daily until delivery. MAIN
      OUTCOME MEASURES: Preterm labour, low birthweight, the occurrence of placental
      abruptions and perinatal mortality. RESULTS: The frequency of severely small for
      gestational age infants (birthweight < 5th centile) was reduced in the aspirin
      treated group to 16% compared with 25% in the placebo group (95% CI-21% to 13%).
      The frequency of delivery before 34 weeks of gestation was 26% in the aspirin
      group and 42% in the placebo group (95% CI--30% to 1%). The perinatal mortality
      was 240/1000 in the aspirin group and 320/1000 in the placebo group (95% CI--22%
      to 6%). None of these reductions was statistically significant. Although the
      frequency of placental abruptions was similar in the two groups, significantly
      more babies died from abruption in the aspirin treated group (91% versus 30%, 95%
      CI 28% to 94%). Low dose aspirin did cause a significant reduction (P = 0.008) in
      deaths from causes other than placental abruption. CONCLUSION: This trial
      revealed a benefit of low dose aspirin therapy in women with raised maternal
      serum alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns,
      but the effect was smaller than expected. Although a reduction in deaths from
      small preterm babies was observed, there was an increase in the number of deaths
      following placental abruption without a significant increase in the number of
      abruptions. We recommend that this should be considered before giving aspirin to
      these high risk women and that other investigators should specifically look for
      this effect.

PMID- 7517180
TI  - Doppler ultrasound of the uteroplacental circulation in the prediction of
      pregnancy outcome in women with raised maternal serum alpha-fetoprotein.
AB  - OBJECTIVE: To determine whether Doppler waveforms from the uteroplacental
      circulation could improve the prediction of pregnancy outcome in women with
      raised maternal serum alpha-fetoprotein and a structurally normal fetus. The
      study further attempts to determine whether the presence of an early diastolic
      notch would constitute a better screening test than waveform patterns. DESIGN: An
      observational study. SETTING: A tertiary referral obstetric service. SUBJECTS:
      All women referred to St George's Hospital with a raised maternal serum alpha
      fetoprotein had waveform measurements from the uteroplacental circulation after
      exclusion of fetal abnormalities. Pregnancy outcome was determined by
      questionnaire sent to the referring clinicians. MAIN OUTCOME MEASURES: Adverse
      perinatal outcome in the form of preterm labour, low birthweight and perinatal
      mortality. RESULTS: Data from 332 cases were available for analysis. Women with a
      normal pattern of uteroplacental waveforms had a perinatal mortality of 9.6/1000.
      Women with a uniform high resistance pattern had a perinatal mortality of
      846/1000, and those with a mixed resistance pattern had a perinatal mortality of
      268/1000. Overall there were 27 cases of placental abruption which accounted for
      eight of the 50 perinatal deaths. The remainder were due to prematurity or low
      birthweight or both. The presence of the early diastolic notch did not improve on
      the waveform patterns in the prediction of perinatal death. CONCLUSION: Women
      with raised maternal serum alpha-fetoprotein and normal Doppler waveform patterns
      from the uteroplacental circulation can be reassured, but mixed or uniform high
      resistance patterns should encourage increased surveillance and a search for
      intervention therapies.

PMID- 7517182
TI  - The cell adhesion molecule, VCAM-1, is selectively elevated in serum in pre
      eclampsia: does this indicate the mechanism of leucocyte activation?
AB  - OBJECTIVE: To determine whether circulating levels of cell adhesion molecules,
      markers of endothelial damage and leucocyte activation, were increased in pre
      eclampsia. DESIGN: Serum was prepared from peripheral venous blood and stored at 
      70 degrees C. The cell adhesion molecules, VCAM-1, E-Selectin and ICAM-1, were
      measured by ELISA. SETTING: Department of Obstetrics and Gynaecology, Royal
      Infirmary, Glasgow. SUBJECTS: Sixteen primigravid women with pre-eclampsia were
      recruited for the study. The preeclampsia group were compared with 18 healthy
      primigravid women with uncomplicated pregnancies. RESULTS: The pre-eclamptic
      group had significantly higher serum levels of the cell adhesion molecule VCAM-1
      (t = 3.673; P < 0.001). There were no significant differences in the adhesion
      molecules ICAM-1 or E-Selectin. CONCLUSIONS: Endothelial damage and dysfunction
      are common to all the pathological features of pre-eclampsia. This study shows
      that concentrations of cell adhesion molecules, which indicate leucocyte
      endothelial attachment and activation, are elevated in the serum of patients with
      pre-eclampsia. Such increases in soluble circulating cell adhesion molecules may
      reflect increased expression of these molecules on the endothelium and thereby
      explain the mechanism for leucocyte activation in pre-eclampsia.

PMID- 7517184
TI  - Platelet activation results in a redistribution of glycoprotein IV (CD36).
AB  - To investigate the possibility that thrombin and/or other platelet activators
      change the platelet surface expression of glycoprotein IV (GPIV, CD36), we used a
      panel of five GPIV-specific monoclonal antibodies (OKM5, 5F1, FA6-152, 8A6, and
      F13) directed against different epitopes. All these antibodies bound to resting
      platelets in a concentration-dependent and saturable manner, as determined by
      flow cytometry of washed platelets. Thrombin (1 U/mL) induced an approximately
      twofold increase in the platelet surface binding of each of these monoclonal
      antibodies. Immunofluorescence microscopy demonstrated an internal pool of GPIV
      that, after thrombin stimulation, redistributed to the platelet surface. In a
      whole-blood flow-cytometric assay, alpha-thrombin and the thromboxane A2 analogue
      U46619 each resulted in an approximately twofold increase in the platelet surface
      binding of OKM5, whereas ADP had a more modest effect, and collagen and
      epinephrine had little effect. The activation-induced up-regulation of the
      platelet OKM5 epitope occurred in vivo as demonstrated by flow cytometric
      analysis of whole blood emerging from a standardized skin puncture site. In
      summary, both in vitro and in vivo platelet activation results in increased
      platelet surface expression of GPIV, as a result of a redistribution of GPIV from
      an internal pool.

PMID- 7517185
TI  - Role of the lipopolysaccharide (LPS)-binding protein/CD14 pathway in LPS
      induction of tissue factor expression in monocytic cells.
AB  - Endotoxic shock is associated with a coagulopathy, organ failure, and death.
      Tissue factor (TF) expression by monocytes exposed to bacterial endotoxin
      (lipopolysaccharide [LPS]) may mediate the coagulopathy and contribute to the
      high mortality of this disease. We examined the role of the LPS-binding protein
      (LBP)/CD14 receptor pathway in the LPS induction of TF expression in human
      monocytic THP-1 cells and peripheral blood monocytes. In THP-1 cells, the
      threshold concentration of LPS required to induce TF activity in serum-free
      medium was reduced 20-fold by purified LBP, which also enhanced TF mRNA
      synthesis. Similarly, monocytes cultured in the presence of serum were induced to
      express TF antigen at LPS concentrations 100 times lower than monocytes cultured
      in serum-free medium. An anti-LBP monoclonal antibody indicated that this effect
      was dependent on the presence of LBP in serum. LPS/LBP induction of TF activity
      and TF antigen expression in these monocytic cells were also inhibited by an anti
      CD14 monoclonal antibody, indicating a requirement for the CD14 receptor. Thus,
      we suggest that low levels of LPS (5 to 100 pg/mL) present during sepsis induce
      TF expression in monocytes via the LBP/CD14-dependent pathway.

PMID- 7517183
TI  - Serum screening for Down's syndrome.

PMID- 7517186
TI  - Effect of membrane surface potential on the uptake of anionic compounds by
      liposomes.
AB  - The effect of membrane surface potential on the uptake of several anionic
      compounds by liposomes (large unilamellar vesicles), which contain various
      amounts of dipalmitoylphosphatidylserine (DPPS), was investigated. The uptake
      amount of four tested anionic compounds (cefixime, benzyloxyindoleacetic acid
      (BOIAA), ceftibuten and S-1006) decreased with an increase in the DPPS content of
      liposomes, and was correlated with the membrane surface potential monitored using
      a fluorescent dye, 8-anilino-1-naphthalene sulfonate (ANS). Moreover, for all of
      the tested anionic compounds, a good correlation was observed between the ratio
      of the uptake value (5 min) by each of the liposomes comprising various amounts
      of DPPS to the uptake value by liposomes containing 10% DPPS and a relative
      membrane surface potential monitored by ANS. On the other hand, the uptake of
      zwitterionic compounds (enoxacin, cephradine and benzyloxytryptophan (BOTP)) was
      independent of DPPS content. These results suggest that the uptake of tested
      anionic compounds by large unilamellar lipid vesicles is dependent on the
      membrane surface potential which originates in the surface negative charge.

PMID- 7517188
TI  - Gene transfer into nonhuman primate CD34+CD11b- bone marrow progenitor cells
      capable of repopulating lymphoid and myeloid lineages.
AB  - We investigated whether rhesus monkey CD34+CD11b- hematopoietic stem cells can be
      transduced with recombinant retroviruses carrying the human adenosine deaminase
      (hADA) gene by co-cultivation with a virus-producing cell line. Following
      autologous transplantation, polymerase chain reaction (PCR) analysis on
      peripheral blood mononuclear cells and granulocytes showed that the hADA
      retrovirus was present in approximately 0.1% of the cells for at least 400 days
      post transplantation in 2 monkeys. Bone marrow that was harvested 16 months after
      transplantation carried ADA-overexpressing myeloid progenitor cells capable of in
      vitro colony formation. In addition, hADA activity could be demonstrated in T
      lymphocytes that were harvested 9 months post transplantation. Thus, in vitro
      transduction of CD34+CD11b- cells led to long-term repopulation of the
      hematopoietic system with transduced cells of lymphoid and myeloid lineages
      expressing the hADA gene. To investigate whether infusion of virus-producing
      cells into a rhesus monkey undergoing autologous bone marrow transplantation
      could lead to in vivo transfer of the recombinant retrovirus, 1 monkey was
      infused with CD34+CD11b- bone marrow cells (BMC) and a large quantity of virus
      producing cells. Few provirus-carrying cells could temporarily be detected in
      this animal. This shows that in vivo gene transfer into a regenerating
      hemopoietic system can occur, albeit at very low efficiency.

PMID- 7517187
TI  - Analysis of the mechanism of glucocorticoid-mediated down regulation of the mouse
      alpha-fetoprotein gene.
AB  - Regulation of alpha-fetoprotein gene expression by dexamethasone was examined in
      vivo and in vitro using primary mouse fetal liver cell cultures. Dexamethasone
      accelerates the developmental down regulation of AFP mRNA pools. However,
      treatment of primary fetal liver cells in culture does not reduce the AFP mRNA
      pool and may stabilize both AFP and albumin gene expression. These results
      indicate that in vivo the effect of dexamethasone may require interaction with
      another tissue or cell type. The mechanism of the dexamethasone mediated
      inhibition of AFP was examined by DNase I footprinting and transient expression
      assays. Two protein-binding regions of the proximal promoter (III and IV) show
      significant homology to the GRE consensus sequence. DNase I footprinting shows
      that only region IV can bind purified GR and competition with GRE
      oligonucleotides indicate that, using adult liver nuclear proteins, no GR is
      bound in either region. Nuclear protein from adrenalectomized mice show the same
      protection as controls. These results indicate that GR may not bind to the AFP
      proximal promoter in the adult. AFP promoter-CAT expression vectors were used to
      further examine the effect of dexamethasone on AFP expression. AFP promoter-CAT
      constructs were inhibited by 10(-6) M dexamethasone; while linking of an AFP
      enhancer to the promoter abolished the effect. We conclude that the in vitro
      effects on transiently expressed AFP directed expression vectors may be a
      function of vector structure and/or characteristics of the cells used whereas the
      in vivo effect may reflect normal regulatory mechanisms.

PMID- 7517191
TI  - Interferon responses in schizophrenia and major depressive disorders.
AB  - The spontaneous and induced interferon (IFN) production in whole blood cultures
      was examined in 45 psychiatric inpatients and in 65 normal controls. Among
      inpatients there were 32 who were chronic schizophrenics (14 women, 18 men) and
      13 who were severely depressed (11 women, 2 men). The analysis of the pooled
      results of assays in the heterogeneous population showed that leukocytes of the
      psychiatric patients produced significantly lower levels of IFN after stimulation
      with virus (NDV), lipopolysaccharide (LPS), and IFN spontaneously released
      without the inducers that control cells. In contrast, there was no difference
      between the psychiatric patients and controls in IFN response to
      phytohemagglutinin and phorbol myristate acetate (PHA + PMA). The results
      apparently confirmed observations made by Moises et al (1985) and Katila et al
      (1989). We have also tested our hypothesis that the statistics may mask the
      individual pattern of IFN response related to the specific psychiatric diagnosis,
      however. In fact, in the group of chronic schizophrenics we have found either
      high or low responders to all IFN inducers (NDV, PHA + PMA and LPS). Furthermore,
      the patients with high IFN response had dominant positive symptoms of
      schizophrenia (delusions, hallucinations, bizarre behavior and thought disorder).
      Whereas, in the patients with low IFN response the negative symptoms prevailed
      (asociality or withdrawal, flat affect, attention impairment, abolition or
      apathy). In plasma samples of schizophrenics, factors were detected that
      transferred a hypersensitivity to the IFN inducers to normal donor leukocytes.
      For instance, in leukocytes cultured in the presence of plasma from
      schizophrenics, there were 71% of high IFN responders after stimulation with NDV,
      versus 26% of high IFN responders in the presence of plasma from normal controls.
      We suggest that the factors may belong to the class of opioid peptides, which
      interact with the production of cytokines including IFNs.

PMID- 7517192
TI  - On the syntactic structure and redundancy distribution of the genetic code.
AB  - By means of an algorithm for finding rules in data, it is shown that the genetic
      code may be written as a codon-tree, independent of amino acid assignments.
      Considering this tree as a structural description, a low-complexity, context-free
      grammar of the code is built and its grammar complexity and grammar redundancy
      calculated. The relationship between the codon-tree and the hierarchy of amino
      acid categorizations previously introduced by the author is investigated.
      Interpreting the obtained code's structure as a record of its evolution, some
      inferences about the divergences of the code series are made.

PMID- 7517190
TI  - In vitro response of blasts to IL-3, GM-CSF, and G-CSF is different for
      individual AML patients: factors that stimulate leukemic clonogenic cells also
      enhance Ara-C cytotoxicity.
AB  - In vivo, growth factors are currently investigated for their capacity to trigger
      leukemic stem cells into cycle and thus overcome kinetic drug resistance. In this
      study, the susceptibility of leukemic clonogenic cells to individual growth
      factors was related to cytosine-arabinoside (Ara-C) sensitivity. The effects of
      interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (G-CSF),
      granulocyte colony-stimulating factor (G-CSF), and combinations of these
      recombinant hematopoietic factors were tested on blast cells of nine acute
      myeloid leukemia (AML) patients. Growth factor responses were assessed in semi
      solid clonogenic assay and in a 10-day liquid culture followed by clonogenic
      assay. Heterogeneity in growth factor response was observed in both test systems,
      resulting in a variable pattern for individual leukemias. In the majority of
      cases (six of nine) the response patterns in the semi-solid and liquid cultures
      were divergent. To test the Ara-C sensitivity, leukemic blasts were exposed in
      liquid to various concentrations of Ara-C in the absence and presence of
      preselected growth factors. After 10 days, the number of surviving leukemic
      colony-forming cells (CFU-L) was assessed. Exposure to Ara-C in the presence of
      optimal stimulatory factor(s) resulted in a 3- to 1000-fold increase of the Ara-C
      toxicity in seven patients. The Ara-C concentrations resulting in 50% inhibition
      of clonogenicity (ID50) were 0.48-123 x 10(-8) M Ara-C in the absence of
      stimulatory growth factors, versus only 0.12-0.40 x 10(-8) M Ara-C in the
      presence of these factors. In two patients, addition of one or more factors
      neither increased the number of CFU-L in liquid nor enhanced the Ara-C toxicity.
      Even in the absence of growth factors the ID50 values in these cases were as low
      as 0.20 and 0.28 x 10(-8) M Ara-C and in the same range as the ID50 values
      observed with maximum growth factor stimulation in the other seven patients.
      These results indicate that Ara-C cytotoxicity can be enhanced by individually
      selected, clonogenic cell growth-promoting hematopoietic factors.

PMID- 7517189
TI  - Gene transfer to freshly isolated human respiratory epithelial cells in vitro
      using a replication-deficient adenovirus containing the human cystic fibrosis
      transmembrane conductance regulator cDNA.
AB  - Cystic fibrosis (CF) results from mutations of the CF transmembrane conductance
      regulator (CFTR) gene and subsequent defective regulation of cAMP-stimulated
      chloride (Cl-) permeability across the apical membrane of epithelial cells. In
      vitro transfer of normal CFTR cDNA corrects this defect, and studies in
      experimental animals have shown successful gene transfer to airway epithelium in
      vivo using a recombinant adenoviral vector containing the human CFTR cDNA
      (AdCFTR), supporting the feasibility of in vivo AdCFTR-mediated gene therapy for
      the respiratory manifestations of CF. One step in applying this therapy to CF
      patients is to evaluate the safety and efficacy of AdCFTR-mediated gene transfer
      in the actual target for human gene therapy, human airway epithelium. The present
      study demonstrates that AdCFTR restores cAMP-stimulated Cl- permeability in human
      CF bronchial epithelial cells. In addition, the study utilizes freshly isolated
      human airway epithelial cells from the nose and/or bronchi of normal individuals
      and/or individuals with CF to demonstrate that after in vitro AdCFTR-mediated
      gene transfer: (i) AdCFTR DNA does not replicate as a function of dose and time;
      (ii) CF epithelial cells express AdCFTR-mediated normal human CFTR mRNA; and
      (iii) CF epithelial cells, including terminally differentiated ciliated cells
      (the most common airway epithelial cell type), express the normal human CFTR
      protein. Together, these data support the use of AdCFTR in human gene therapy
      trials and suggest that biologic efficacy should be achievable in vivo.

PMID- 7517194
TI  - Modification of striatal arginine and citrulline metabolism by nitric oxide
      synthase inhibitors.
AB  - The effects of NG-substituted L-arginine (ARG) analogues on striatal ARG and
      citrulline (CIT) levels were investigated using in vivo microdialysis technique.
      A microdialysis probe was implanted into the striatum of anaesthesized Sprague
      Dawley rats. Direct intrastriatal perfusion with 1 mM NG-nitro-L-arginine methyl
      ester (n = 8) increased striatal ARG release and decreased CIT release,
      suggesting suppressed NO synthase activity in the tissue. On the other hand, 1 mM
      NG-monomethyl-L-arginine (L-NMMA) (n = 6) evoked a persistent increase in both
      ARG and CIT. Considering that 4-320 microM L-ARG (n = 8) failed to increase CIT
      formation, CIT seems to be synthesized in the striatal tissue from L-NMMA by the
      enzyme that has been demonstrated in the kidney and aortic endothelium (NG,NG
      dimethylarginine dimethyl-aminohydrolase).

PMID- 7517193
TI  - The regularity of changes of the Chou-Fasman parameters within the genetic code.
AB  - It has been shown that Chou-Fasman conformational parameters of amino acids,
      which reflect their ability to adopt a definite conformation within the peptide
      chain, change very regularly within the genetic code, arranged in the manner
      discussed recently by Siemion and Stefanowicz (1992a) (BioSystems 27, 77-84). Two
      mutually perpendicular C2 axes of pseudosymmetry appear in the center of the
      diagrams (between ACY and ACR threonine codons) presenting the changes of P alpha
      and P beta parameters. The left and right parts of diagrams superimpose on each
      other quite well when the symmetry operation involving a proper axis is
      performed. This phenomenon is due, in our opinion, to the regular arrangement of
      equivalent codons in the 'one-step mutation' ring formed by 64 triplets of the
      genetic code.

PMID- 7517196
TI  - Nitric oxide synthase expression in vagal complex following vagotomy in the rat.
AB  - Peripheral axotomy of the spinal nerve and avulsion of the ventral roots have
      been found to induce increase in expression of nitric oxide synthase (NOS) in the
      spinal motor neurones and the dorsal root ganglion. The present study
      investigated changes of NOS, using NADPH-diaphorase (NADPH-d) reactivity as the
      marker, in vagal complex after axotomy in the rat. Eight days after left cervical
      vagotomy the NADPH-d reactivity was found to be markedly enhanced in the dorsal
      motor nucleus of the vagus nerve, the ambiguus nucleus, the solitary tract and
      the nucleus of the tractus solitarius, and the nodose ganglion. This study offers
      the first evidence of changes in NOS expression in cranial visceral components
      following axotomy.

PMID- 7517195
TI  - Tolerance to diacetyl morphine antinociception: effects on brain serotonin.
AB  - The effects of 5 mg kg-1 diacetyl morphine (DAM) on brain serotonin metabolism of
      rats were investigated following tolerance to the antinociceptive effects of 2.5
      mg kg-1 DAM. Brain levels of tryptophan and 5-hydroxy indoleacetic acid (5-HIAA)
      were higher in the DAM-tolerant rats killed 24 h after last daily administration
      of 2.5 mg kg-1 DAM. Administration of 5 mg kg-1 DAM produced less antinociception
      in DAM-tolerant than DAM-naive rats and increased brain tryptophan concentration
      in both tolerant and naive rats. 5-HIAA concentrations increased only in naive
      rats. Combined use of drugs interfering with brain 5-HT turnover along with
      opiates may be of future benefit for the treatment of chronic pain.

PMID- 7517197
TI  - Cerebellar injury induces NOS in Purkinje cells and cerebellar afferent neurons.
AB  - Purkinje cells of the cerebellar cortex and neurons of most precerebellar nuclei
      are conspicuous by the absence of constitutive (neuronal) nitrix oxide synthase
      (nNOS). Here we show that following mechanical, chemical or thermal injury to the
      cerebellar cortex there is an induction of nNOS in Purkinje cells as identified
      with NADPH-diaphorase (NADPH-d) histochemistry and nNOS immunocytochemistry.
      Induced nNOS and NADPH-d (inNOS/NADPH-d) first appeared 72 hours post-treatment
      and persisted in excess of 8 weeks. Precerebellar neurons throughout the brain
      stem also exhibited induced nNOS and NADPH-d with a similar time course. These
      results indicate that brain lesions can induce nNOS in local neurons and in
      neurons which are afferent to the leasioned area.

PMID- 7517200
TI  - [Methodology for oral presentations on advances in gastroenterology].

PMID- 7517199
TI  - Nitric oxide synthase-containing nerve fibres and neurones in the gall bladder
      and biliary pathways of the guinea-pig.
AB  - We investigated the distribution pattern of nitric oxide (NO) synthesizing nerve
      cell bodies and axons in the biliary system of the guinea-pig using
      immunohistochemistry for nitric oxide synthase (NOS). Nerve fibres staining for
      NOS were found to contact non-vascular smooth myocytes and to course beneath the
      epithelium. No perivascular NOS fibres were observed. The innervation density
      varied in different parts of the biliary tree. The lower portion of the common
      bile duct was more richly innervated than the remaining parts of the duct system.
      NOS-containing neurones encompassed a subpopulation of intramural ganglion cells.
      Sympathetic neurones in the coeliac ganglion were not stained. It is suggested
      that intrinsic NOergic neurones are involved in inhibitory motor control of the
      biliary musculature, including the sphincter of Oddi.

PMID- 7517198
TI  - cGMP acts within cerebellar Purkinje cells to produce long term depression via
      mechanisms involving PKC and PKG.
AB  - Long term depression (LTD) of parallel fibre-Purkinje cell responses may result
      from desensitization of AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid) type glutamate receptors, for which a cascade of reactions involving
      calcium, inositol-1,4,5-trisphosphate, nitric oxide (NO), guanosine-3'5'
      monophosphate (cGMP) and protein kinases C and G has been previously proposed.
      The involvement of cGMP in synaptic LTD was confirmed by direct injection of cGMP
      and 8-bromo-cGMP (8-Br-cGMP) into the dendrites of Purkinje cells. Pairing
      injections with parallel fibre stimulation led to a LTD of synaptic transmission
      which both occluded and was occluded by heterosynaptically induced LTD.
      Inhibition of either protein kinases C or G prevented induction of both forms of
      LTD.

PMID- 7517202
TI  - Stem cell factor promotes proliferation of human primitive megakaryocytic
      progenitors, but not megakaryocytic maturation.
AB  - The effect of soluble c-kit ligand (stem cell factor, SCF) on human
      megakaryocytopoiesis of the cells from umbilical cord blood was evaluated in a
      methylcellulose culture containing human plasma. SCF alone did not stimulate
      megakaryocyte colony formation by non-phagocytic mononuclear cells (NPMNC), but
      did so in combination with interleukin (IL)-3, dose-dependently. This stimulatory
      effect was exhibited more strongly on large megakaryocyte colonies than on small
      ones. The effects of SCF + IL-3 on the number and size of megakaryocyte colonies
      exceeded those of IL-6 + IL-3 or of IL-11 + IL-3. The synergistic interaction of
      SCF with IL-3 was confirmed by using CD34-positive cells. In particular, addition
      of SCF to the culture with optimal and suboptimal concentrations of IL-3,
      significantly increased mixed megakaryocyte colony formation as compared with IL
      3 alone. Although SCF in combination with IL-6 or IL-11 induced megakaryocyte
      colonies from NPMNC, these interactions disappeared entirely in the culture using
      CD34-positive cells. IL-6 or IL-11 significantly increased the size and DNA
      content of megakaryocytes in the presence of IL-3, while SCF did not affect, or
      rather decreased, the DNA content. These findings suggest that SCF promotes more
      strongly the proliferation of primitive rather than mature megakaryocytic
      progenitors, but does not affect megakaryocytic maturation.

PMID- 7517203
TI  - Isolation and characterization of human bone marrow microvascular endothelial
      cells: hematopoietic progenitor cell adhesion.
AB  - To examine potential mechanisms by which hematopoiesis may be regulated by
      endothelial cells within the bone marrow (BM) microenvironment, we have devised a
      technique for the in vitro study of the interaction of human BM microvascular
      endothelial cells (BMEC) with hematopoietic cells. Microvessels isolated by
      collagenase digestion of spicules obtained from filtered BM aspirate were plated
      on gelatin-coated plastic dishes, and colonies of endothelial cells grown from
      microvessel explants were further purified by Ulex europaeus lectin affinity
      separation. BMEC monolayers isolated by this technique grew in typical
      cobblestone fashion, stained positively with antibody to factor VIII/von
      Willebrand factor, and incorporated acetylated LDL. Immunohistochemical studies
      showed that BM microvessels and BMEC monolayers express CD34, PECAM, and
      thrombospondin. Incubation of resting BMEC with BM mononuclear hematopoietic
      cells resulted in the selective adhesion of relatively large numbers of CD34+
      progenitor cells and megakaryocytes. The binding of purified BM-derived CD34+
      progenitor cells to BMEC was dependent on divalent cations and was partially
      blocked by antibodies to CD34. IL-1 beta treatment of BMEC monolayers resulted in
      an increase of CD34+ progenitor cell adhesion by mechanisms independent of CD34
      or divalent cations. BMEC exhibit specific affinity for CD34+ progenitor cells
      and megakaryocytes, suggesting that the BM microvasculature may play a role in
      regulating the trafficking, proliferation, and differentiation of lineage
      specific hematopoietic elements, and possibly of pluripotent stem cells within
      the CD34+ population.

PMID- 7517201
TI  - Effects of stem cell factor (SCF) on human marrow neutrophil,
      neutrophil/macrophage mixed, macrophage and eosinophil progenitor cell growth.
AB  - The effects of stem cell factor (SCF) on the subpopulations of
      granulocyte/macrophage colony-forming units (CFU-GM) were examined. Hematopoietic
      progenitor cells were enriched from normal adult bone marrow specimens by
      immunomagnetic beads using an anti-CD34 antibody and lineage marker antibodies
      for positive selection and negative selection, respectively. SCF enabled
      neutrophil and neutrophil/macrophage mixed progenitors to respond to
      granulocyte/macrophage colony-stimulating factor (GM-CSF) or interleukin 3 (IL-3)
      and to develop the colony and further cluster formation. The neutrophil colonies
      stimulated by GM-CSF or IL-3 consisted mainly of immature cells, while the
      colonies stimulated by granulocyte colony-stimulating factor (G-CSF) consisted of
      mature neutrophils irrespective of the addition of SCF. In macrophage and
      eosinophil lineages, SCF augmented the colony formation in the presence of GM-CSF
      or IL-3, whereas the enhancement of total progenitor cell growth (colonies plus
      clusters) was not so marked as compared with the neutrophil lineage. Time-course
      observation revealed that SCF could stimulate macrophage and eosinophil
      progenitors to form colonies rapidly. These findings indicate that SCF acts on
      late myeloid progenitor cells in manners different from the lineages of
      commitment.

PMID- 7517204
TI  - Generation of T cells from cytokine-mobilized peripheral blood and adult bone
      marrow CD34+ cells.
AB  - The present study compared the T-cell progenitor content of CD34+ lineage (Lin)-
      cells isolated from normal adult bone marrow (ABM) and mobilized peripheral blood
      (MPB). Both cell populations were found to differentiate into T cells when
      injected into human fetal thymi implanted into severe combined immunodeficient
      mice. Cytokine-MPB cells were less efficient than ABM cells in engrafting in the
      fetal human thymus, although both gave rise to thymocytes with identical
      phenotypes based on the analysis of CD1a, CD3, CD4, and CD8 expression.
      Thymocytes derived from adult CD34+ Lin- cells were capable of fully
      differentiating into mature CD3+ T cells expressing either the T-cell receptor
      (TCR) gamma delta or the TCR alpha beta (the later associated with CD4 or CD8),
      showing that the T-cell progenies of adult CD34+ cells were polyclonal and
      functional. Our data indicate that human MPB CD34+ cells are qualitatively
      identical to their BM counterparts, and demonstrate the existence of T-lymphoid
      progenitor cell activity in MPB.

PMID- 7517205
TI  - Hepatocyte growth factor stimulates expression of plasminogen activator inhibitor
      type 1 and tissue factor in HepG2 cells.
AB  - HGF is a powerful mitogen for both rat and human hepatocytes, epithelial cells
      and endothelial cells in vitro, and is angiogenic in vivo. It has considerable
      homology with plasminogen and has been shown to upregulate urokinase-type
      plasminogen activator (u-PA) in endothelial cells as well as u-PA and its
      receptor in kidney epithelial cells. In this study, we report that human
      recombinant HGF stimulates expression of plasminogen activator inhibitor type 1
      (PAI-1) and tissue factor (TF) in the human hepatoma cell line HepG2. PAI-1
      antigen as determined by a specific enzyme-linked immunosorbent assay increased
      up to threefold in conditioned media of HepG2. This increase was dose dependent
      with maximum stimulation achieved with a concentration of 50 ng/mL of hepatocyte
      growth factor (HGF). PAI-1 antigen also increased up to fourfold in the
      extracellular matrix in HGF treated HepG2. The production of the PAI-1 binding
      protein vitronectin (Vn) was not affected by HGF. In contrast, TF activity in
      HepG2 treated with HGF increased up to twofold. As determined by Northern
      blotting, PAI-1 and TF-specific mRNA were increased significantly in the presence
      of HGF, whereas Vn mRNA was not affected. The increase in PAI-1 and TF mRNA was
      also seen when HepG2 were incubated with HGF in the presence of cycloheximide,
      thereby indicating that de novo protein synthesis is not required to mediate the
      effect. u-PA could be detected neither in unstimulated or HGF-stimulated HepG2
      cells on the antigen level nor on the mRNA level. In conclusion, our data give
      evidence that HGF, in addition to its proliferative effect for different cell
      types, is also involved in the local regulation of fibrinolysis and coagulation.
      One could speculate that HGF might modulate processes requiring matrix
      degradation by increasing the expression of the protease u-PA in one cell type
      and by upregulating the expression of the serine protease inhibitor PAI-1 in a
      different cell type. Because u-PA has been shown to activate latent HGF to the
      active form, it could furthermore be speculated that by upregulating PAI-1, which
      in turn could inhibit u-PA, HGF might regulate its own activation.

PMID- 7517206
TI  - Neutrophil cathepsin G modulates the platelet surface expression of the
      glycoprotein (GP) Ib-IX complex by proteolysis of the von Willebrand factor
      binding site on GPIb alpha and by a cytoskeletal-mediated redistribution of the
      remainder of the complex.
AB  - The effects of neutrophil cathepsin G on the glycoprotein (GP) Ib-IX complex of
      washed platelets were examined. Cathepsin G resulted in a concentration- and time
      dependent decrease in the platelet surface GPIb-IX complex, as determined by flow
      cytometry, binding of exogenous von Willebrand factor (vWF) in the presence of
      ristocetin, and ristocetin-induced platelet agglutination. Cathepsin G resulted
      in proteolysis of the vWF binding site on GPIb alpha (defined by monoclonal
      antibody [MoAb] 6D1), as determined by increased supernatant glycocalicin
      fragment (a proteolytic product of GPIb alpha); decreased total platelet content
      of GPIb; and lack of effect of either cytochalasin B (an inhibitor of actin
      polymerization), prostaglandin I2 (an inhibitor of platelet activation), or prior
      fixation of the platelets. However, cathepsin G resulted in minimal decreases in
      the binding to fixed platelets of MoAbs TM60 (directed against the thrombin
      binding site on GPIb alpha) and WM23 (directed against the macroglycopeptide
      portion of GPIb alpha). In contrast to its proteolytic effect on GPIb alpha, the
      cathepsin G-induced decrease in platelet surface GPIX and the remnant of the GPIb
      IX complex (defined by MoAbs FMC25 and AK1) was via a cytoskeletal-mediated
      redistribution, as determined by lack of change in the total platelet content of
      GPIX and the GPIb-IX complex; complete inhibition by cytochalasin B,
      prostaglandin I2, and prior fixation of platelets. Experiments with Serratia
      protease-treated and Bernard-Soulier platelets showed that neither platelet
      surface GPIb nor cathepsin G-induced proteolysis of GPIb were required for the
      cathepsin G-induced redistribution of the remnant of the GPIb-IX complex or the
      cathepsin G-induced increase in platelet surface P-selectin. In summary,
      neutrophil cathepsin G modulates the platelet surface expression of the GPIb-IX
      complex both by proteolysis of the vWF binding site on GPIb alpha and by a
      cytoskeletal-mediated redistribution of the remainder of the complex. Prior
      studies show that, although thrombospondin 1, antiserine proteases, and plasma
      are all inhibitors of cathepsin G, the effects of cathepsin G on platelets,
      including an increase in surface GPIIb-IIIa, occur during close contact between
      neutrophils and platelets in a protective microenvironment (eg, thrombosis and
      local inflammation).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7517207
TI  - Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium
      dependent epitopes on the glycoprotein IIb/IIIa complex.
AB  - Drug-dependent IgG antibodies (DDAb) induced by sulfamethoxazole (SMX) and
      sulfisoxazole (SIX) were identified by flow cytometry in 15 patients who
      developed thrombocytopenia while taking one of these medications. Fourteen of the
      15 DDAb were specific solely for the glycoprotein (GP)IIb/IIIa complex, and 13 of
      these reacted wholly or in part with epitopes present only on the intact
      GPIIb/IIIa heterodimer. None of 12 SMX-induced DDAb cross-reacted with SIX, but
      one of three SIX-induced antibodies reacted with SMX. Each of 10 SMX-induced DDAb
      tested reacted with the N1-acetyl metabolite of SMX, but only one reacted fully
      with the N4-acetyl derivative. Detection of the SMX- and SIX-dependent antibodies
      was facilitated by using bovine serum albumin (BSA) to achieve suspension of
      these weakly soluble drugs in an aqueous medium. Our findings indicate that DDAb
      induced by SMX and SIX, in contrast to those induced by quinidine and quinine,
      are mainly specific for GPIIb/IIIa and react preferentially with calcium
      dependent epitopes present only on the intact GPIIb/IIIa heterodimer.

PMID- 7517208
TI  - The N-domain of the biliary glycoprotein (BGP) adhesion molecule mediates
      homotypic binding: domain interactions and epitope analysis of BGPc.
AB  - The biliary glycoproteins (BGPs) represent a group of at least eight
      differentially spliced molecules belonging to the carcinoembryonic antigen (CEA)
      subgroup of the CEA family. These molecules are recognized by the CD66 monoclonal
      antibodies (MoAbs) and function as homotypic and heterotypic adhesion molecules.
      The extracellular region of the BGPc splice variant comprises an N-terminal IgV
      like domain and three IgC2-set domains (A1, B1, and A2). Using soluble
      recombinant BGP domain variants, we demonstrate in this report that the N
      terminal domain mediates homotypic adhesion. Furthermore, this adhesion is both
      temperature- and cation-dependent. The soluble domain variants of BGP are ideal
      molecules for epitope mapping. Using these constructs, we have mapped 11 MoAbs
      that react with the CEA family to different domains of BGPc and have shown that
      the CD66 MoAbs, YTH71.3.2 and CLBgran 10 (M38), recognize epitopes in the N
      terminal domain.

PMID- 7517209
TI  - Cytokine gene expression in B-cell chronic lymphocytic leukemia: evidence of
      constitutive interleukin-8 (IL-8) mRNA expression and secretion of biologically
      active IL-8 protein.
AB  - To extent our knowledge on the cytokines possibly involved in the pathophysiology
      of B-cell chronic lymphocytic leukemia (B-CLL), the mRNA expression of a panel of
      10 cytokines was investigated on purified B-CLL cells using a reverse
      transcriptase polymerase chain reaction method. Whereas negative RT-PCR signals
      were recorded for interleukin-1 alpha (IL-1 alpha), IL-2, IL-3, IL-4, IL-5, IL-7,
      tumor necrosis factor beta (TNF beta), and granulocyte-macrophage colony
      stimulating factor, we detected the expression of IL-1 beta, IL-6 and TNF alpha.
      Furthermore, the constitutive expression of IL-8 mRNA was observed in all 17 B
      CLL samples analyzed. mRNA expression was associated with the capacity of the
      leukemic cells to release IL-8 both constitutively (4.6 +/- 8.1 SD ng/mL) and, to
      a further extent, after stimulation (14.5 +/- 19.4 ng/mL). The circulating levels
      of IL-8 were also evaluated in 12 untreated B-CLL sera samples and the overall
      mean level was significantly higher (P < .01) than in normal sera. In addition,
      supernatants of purified B-CLL cells cultured in the presence of 12-O
      tetradecanoylphorbol-13-acetate showed chemotactic activity towards neutrophils;
      this activity was neutralized in the presence of an anti-IL-8 antiserum. The mRNA
      for IL-8 was absent in five B-cell preparations from hairy cell leukemia cases
      and in four B-cell lines. Normal tonsil CD5+ B cells showed a low expression of
      IL-8 mRNA only in two of the nine preparations tested and the overall quantity of
      IL-8 released by these cells after 3 days' incubation was significantly lower
      compared with that released by B-CLL cells (0.4 +/- 0.3 and 1.6 +/- 0.9 ng/mL
      under basal and stimulated conditions, respectively). These findings point to an
      involvement of a member of the proinflammatory chemokine supergene family in
      human CD5+ B lymphocytes. The different IL-8 behavior observed between B-CLL
      cells and their normal counterpart is likely to reflect an activation state of
      the leukemic population.

PMID- 7517210
TI  - Serum CD44 in malignant lymphoma: an association with treatment response.
AB  - CD44, a cell surface glycoprotein, is involved in lymphocyte trafficking from the
      blood to lymphatic tissues, and is of importance in dissemination of lymphoma. A
      variant form of CD44 that has additional amino acids in the common protein
      backbone (CD44v6) also seems to play a role in the metastatic dissemination of
      malignancies. We measured serum CD44 and CD44v6 in 34 patients with lymphoma and
      in healthy controls by dot blot assay. Small amounts of both CD44 (range, 10 to
      80 ng/mL) and CD44v6 could be detected in sera of all controls. Serum CD44 was
      elevated in all patients with lymphoma before treatment (range, 70 to > 2,000
      ng/mL, P < .0001), and CD44v6 was also slightly elevated. Serum CD44 levels
      correlated with response to treatment. Patients with complete response achieved
      similar CD44 levels as the controls, whereas those with progressive disease had
      increased serum CD44 levels. We conclude that both the standard and the variant
      form of CD44 are detectable in sera of healthy individuals, and that serum CD44
      may be useful in monitoring treatment response in patients with lymphoma.

PMID- 7517213
TI  - Interleukin-2-dependent T-cell lines established from paroxysmal nocturnal
      hemoglobinuria patients.
AB  - Peripheral blood T lymphocytes obtained from two patients with paroxysmal
      nocturnal hemoglobinuria (PNH) were immortalized with human T-lymphotropic virus
      type 1 (HTLV-1). These cells showed interleukin-2 (IL-2)-dependent cell growth in
      culture. Cell surface analysis showed that they had the phenotype of a
      helper/inducer T subset that was positive for CD2, CD3, and CD4, but negative for
      CD8, similar to adult T-cell leukemia cells induced by HTLV-1. These cell lines
      lacked glycosylphosphatidylinositol (GPI)-anchored proteins, CDw52, CD55 (decay
      accelerating factor; DAF), and CD59 on the cell surface, whereas intracellular
      DAF protein was detected. These T-subset cell lines with a PNH phenotype did not
      synthesize GPI anchor, whereas a control cell line, similarly prepared from the T
      cells of a healthy volunteer, produced the anchor. The control cells expressed
      CDw52, DAF, and CD59 on the cell surface and showed the phenotype of a
      helper/inducer subset. Southern blot analysis confirmed the clonality of each
      cell line. These CD4+ T-cell lines with a PNH phenotype and a subset-matched
      control counterpart could be a useful model for PNH investigation.

PMID- 7517212
TI  - NB4 cells show bilineage potential and an aberrant pattern of neutrophil
      secondary granule protein gene expression.
AB  - NB4 is an acute promyelocytic leukemia cell line that has been shown to be
      inducible to terminal neutrophil maturation with all-trans retinoic acid (ATRA).
      HL60 cells are differentially inducible with 12-O-tetradecanoylphorbol-13-acetate
      (TPA) or dimethyl sulfoxide (DMSO) to monocytes or granulocytes, respectively.
      HL60 cells induced with DMSO undergo defective neutrophil maturation, manifested
      by a coordinate failure of secondary granule protein gene expression. We observed
      a similar defect in granulocytic maturation in ATRA-induced NB4 cells. In
      addition, because normal promyelocytes are known to have bilineage potential, we
      have investigated differentiation along monocytoid lines induced with TPA. We
      observed a striking phenotypic change along monocytoid/macrophage lines with TPA
      induction. Flow cytometry showed a TPA-induced increase in HLA-DR expression, and
      Northern blot analysis showed induction of expression of CD18, c-fos, and human
      neutrophil gelatinase (HNG). HNG is unique among the neutrophil secondary granule
      protein genes in that it is expressed in both the neutrophil and monocyte
      lineages. This again parallels our findings in TPA-induced HL60 cells, which
      retain the ability to express HNG. These findings confirm bilineage potential in
      NB4 cells. They also support the hypothesis of coordinate neutrophil secondary
      granule protein gene expression and a defect in this control as part of the
      leukemic phenotype.

PMID- 7517211
TI  - HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a
      previously unrecognized form of acute leukemia potentially misdiagnosed as French
      American-British acute myeloid leukemia-M3.
AB  - We have identified and characterized a previously unrecognized form of acute
      leukemia that shares features of both myeloid and natural killer (NK) cells. From
      a consecutive series of 350 cases of adult de novo acute myeloid leukemia (AML),
      we identified 20 cases (6%) with a unique immunophenotype: CD33+, CD56+, CD11a+,
      CD13lo, CD15lo, CD34+/-, HLA-DR-, CD16-. Multicolor flow cytometric assays
      confirmed the coexpression of myeloid (CD33, CD13, CD15) and NK cell-associated
      (CD56) antigens in each case, whereas reverse transcription polymerase chain
      reaction (RT-PCR) assays confirmed the identity of CD56 (neural cell adhesion
      molecule) in leukemic blasts. Although two cases expressed CD4, no case expressed
      CD2, CD3, or CD8 and no case showed clonal rearrangement of genes encoding the T
      cell receptor (TCR beta, gamma, delta). Leukemic blasts in the majority of cases
      shared unique morphologic features (deeply invaginated nuclear membranes, scant
      cytoplasm with fine azurophilic granularity, and finely granular Sudan black B
      and myeloperoxidase cytochemical reactivity) that were remarkably similar to
      those of acute promyelocytic leukemia (APL); particularly the microgranular
      variant (FAB AML-M3v). However, all 20 cases lacked the t(15;17) and 17 cases
      tested lacked the promyelocytic/retinoic acid receptor alpha (RAR alpha) fusion
      transcript in RT-PCR assays; 12 cases had 46,XX or 46,XY karyotypes, whereas 2
      cases had abnormalities of chromosome 17q: 1 with del(17)(q25) and the other with
      t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/RAR alpha fusion
      transcript. All cases tested (6/20), including the case with t(11;17), failed to
      differentiate in vitro in response to all-trans retinoic acid (ATRA), suggesting
      that these cases may account for some APLs that have not shown a clinical
      response to ATRA. Four of 6 cases tested showed functional NK cell-mediated
      cytotoxicity, suggesting a relationship between these unique CD33+, CD56+, CD16-
      acute leukemias and normal CD56+, CD16- NK precursor cells. Using a combination
      of panning and multiparameter flow cytometric sorting, we identified a normal
      CD56+, CD33+, CD16- counterpart cell at a frequency of 1% to 2% in the peripheral
      blood of healthy individuals. Our studies suggest that this form of acute
      leukemia may arise from transformation of a precursor cell common to both the
      myeloid and NK cell lineages; thus we propose the designation myeloid/NK acute
      leukemia. Recognition of this new leukemic entity will be important in
      distinguishing these ATRA-nonresponsive cases from ATRA-responsive true APL.

PMID- 7517216
TI  - Expression of interleukin-1 beta gene in candidate human hematopoietic stem
      cells.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect
      interleukin-1 beta (IL-1 beta) mRNA in candidate human hematopoietic stem cells.
      The cells, obtained from adult bone marrow (BM) or umbilical cord blood, had a
      CD34+ CD45RAlo CD71lo phenotype and were further fractionated into CD38+ and CD38
      or Thy-1+ and Thy-1- subpopulations. The purity of these fractions was always
      more than 99%. IL-1 beta and CD34 mRNA were detected in pools of 30 BM-derived
      CD34+ CD45RAlo CD71lo cells. To further exclude any contribution by contaminating
      cells, individual cells were analyzed for CD34 and IL-1 beta mRNA. Positive
      results were obtained with 2 of 5 individual BM-derived CD34+ CD45RAlo CD71lo
      CD38+ cells isolated by micromanipulation after overnight culture in serum-free
      medium without any exogenous cytokines, and 1 of 10 individual CD34+ CD45RAlo
      CD71lo CD38- cells isolated immediately after sorting. Moreover, of 10 pools of
      three BM-derived CD34+ CD45RAlo CD71lo cells cultured overnight in the presence
      of a mixture of various cytokines (Steel factor, IL-3, IL-6, macrophage colony
      stimulating factor [M-CSF], erythropoietin, and IL-3/granulocyte-macrophage
      colony-stimulating factor [GM-CSF] fusion protein), 5 were positive for IL-1 beta
      mRNA. This result was compatible with more than 20% (95% confidence limit 0.06
      0.61) of the BM cells with the CD34+ CD45RAlo CD71lo phenotype expressing IL-1
      beta mRNA. IL-1 beta expression was also consistently observed from day 0 to day
      9 in liquid cultures of cord-blood-derived CD34+ CD45RAlo CD71lo Thy-1+ or Thy-1-
      cells. The cultures contained the same combination of cytokines and resulted in
      an expansion of cell numbers of up to 400-fold. GM-CSF mRNA was not detected in
      the equivalent of 75 cells at any day, even though it could be detected with high
      sensitivity in control stromal cells. Because IL-1 beta is a powerful and
      pleiotropic biomodulator of cytokines and adhesion molecules, our observations
      suggest that at least some primitive hematopoietic cells do not merely respond
      passively to signals from their environment, but may themselves regulate the
      paracrine production of cytokines from neighboring stromal cells.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7517214
TI  - A potential regulatory region for the expression of fetal hemoglobin in sickle
      cell disease.
AB  - We describe a 0.5-kb region located 1.65 to 1.15 kb upstream of the G gamma fetal
      globin gene with three polymorphisms of erythroid and ubiquitous nuclear protein
      binding motifs (GATA, CRE, and a new protein binding site). These three
      polymorphisms result in high-affinity and low-affinity motifs for nuclear
      proteins, and are combined in four arrangements called pre-G gamma frameworks (pG
      gamma Fs). Each pG gamma F is linked with one of the major haplotypes of the beta
      globin gene cluster observed in sickle cell disease (SCD) associated with
      different mean levels of hemoglobin F (Hb F) expression (P < .001). This strong
      linkage and the differing affinities suggest that this region may be involved in
      the modulation of Hb F expression in SCD.

PMID- 7517215
TI  - Induction of fetal hemoglobin production in subjects with sickle cell anemia by
      oral sodium phenylbutyrate.
AB  - Intravenous arginine butyrate has been shown to increase fetal hemoglobin (HbF)
      in sickle cell and thalassemia patients. Recently, we observed that sodium 4
      phenylbutyrate, a drug administered orally to treat urea cycle disorders,
      increases HbF production in nonanemic children and adults. We treated six
      subjects with sickle cell disease over a period of 14 to 179 days. All subjects
      received their initial therapy of 9 to 13 g/m2/day as 0.5-g tablets of sodium 4
      phenylbutyrate as inpatients. All subjects showed a rapid increase in the
      percentage of F-reticulocytes (pretreatment, 1% to 20%; posttreatment, 10% to
      44%). Four subjects were treated only 11 to 25 days as inpatients. Two of these
      four subjects failed to respond to the outpatient component because of their
      inability to maintain an intake of 30 to 40 tablets per day. One subject (C)
      developed a rash at day 10 and discontinued treatment at day 14. Another subject
      (B) was transfused for a painful crisis on day 25. Subject A, treated for 179
      days, has an increased percentage of F cells, from 54% to 77%, and increased HbF
      levels, from 10.6% to 18%. Subject F, treated for 154 days, has an increased
      percentage of F cells, from 59% to 73%, and an increased percentage of HbF, from
      10.4% to 16%. All subjects showed some increase in weight. Subject A developed
      mild transient ankle edema. Myelotoxicity was not seen in any treated patient.
      Oral administration of sodium 4-phenylbutyrate rapidly increases F-cell
      production in sickle cell disease.

PMID- 7517217
TI  - Functional and biochemical analysis of the cloned Duffy antigen: identity with
      the red blood cell chemokine receptor.
AB  - The Duffy blood group antigen has been postulated to be a receptor on red blood
      cells (RBCs) for the malarial parasite Plasmodium vivax and a promiscuous
      receptor for the chemokine superfamily of inflammatory proteins. Recently, the
      Duffy antigen glycoprotein D cDNA has been cloned (Chaudhuri et al: Proc Natl
      Acad Sci USA 90:10793, 1993). We have analyzed the binding properties of the
      cloned Duffy antigen. Duffy-antigen cDNAs expressed in human embryonic kidney
      cells produced cell-surface proteins that reacted with two known anti-Duffy
      monoclonal antibodies. Direct ligand binding and displacement experiments using
      recombinant chemokine proteins also show that the cloned Duffy protein is the RBC
      chemokine receptor. Radiolabeled chemokines of both the C-C (RANTES and MCP-1)
      and C-X-C (IL-8 and MGSA/gro) subclasses bound reversibly to transfected cells
      with dissociation constants in the nanomolar range. Chemokines of either class
      displaced heterologous chemokines, indicating that they were competing for a
      single site on the transfected cells. Although the chemokines bound to the
      transfected cells with high affinity, there was no evidence for signal
      transduction, as measured by transient increases in intracellular calcium ion
      concentration, through the Duffy antigen/RBC chemokine receptor in transfected
      cells. Lastly, we have performed a computer analysis on the amino acid structure
      of the Duffy antigen/RBC chemokine receptor. Although the cloned Duffy antigen
      has been postulated to be a nine-transmembrane-spanning receptor, our analysis
      suggests that the molecule most likely belongs to the seven-transmembrane
      spanning receptor superfamily and is therefore similar to other chemokine
      receptors previously identified.

PMID- 7517218
TI  - CD34+ peripheral blood progenitors as a target for genetic correction of the two
      flavocytochrome b558 defective forms of chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) can result from any of four single gene
      defects involving components of the superoxide (O2-.)-generating phagocyte NADPH
      oxidase (phox). The phox transmembrane flavocytochrome b558 is composed of two
      peptides, gp91phox and p22phox. Mutations of gp91phox cause X-linked CGD, whereas
      mutations of p22phox cause one of the three autosomal recessive forms of CGD. We
      used the Maloney leukemia virus-based MFG retrovirus vector to produce
      replication defective retroviruses encoding gp91phox or p22phox. To maximize
      viral titer MFG retroviruses do not contain internal promoter or resistance
      elements. Epstein-Barr virus transformed B-lymphocyte cell lines (EBV-B) derived
      from normal individuals contain phox components and produce O2-., whereas those
      derived from CGD patients show the CGD defect. Transduction of gp91phox or
      p22phox-deficient CGD EBV-B lines resulted in correction of O2-. production from
      a barely detectable baseline to an average 7.2% and 13.8% of normal control,
      respectively, without any selective regimen to enrich for transduced cells. CD34+
      hematopoietic progenitor cells, the therapeutic target for gene therapy of CGD,
      were isolated from peripheral blood of CGD patients, transduced with MFG-phox
      retroviruses, and differentiated in culture to mature phagocytes. Transduction of
      progenitors corrected the gp91phox (seven patients) and p22phox (two patients)
      CGD phagocyte oxidase defect to 2.5% and 4.9% of normal O2-. production,
      respectively, representing an 87-fold and 161-fold increase. These studies show
      correction of flavocytochrome b558-deficient CGD in primary hematopoietic
      progenitors, providing a basis for development of gene therapy for the X-linked
      gp91phox and autosomal p22phox-deficient forms of CGD.

PMID- 7517219
TI  - Mast cell growth factor modulates CD36 antigen expression on erythroid
      progenitors from human bone marrow and peripheral blood associated with ongoing
      differentiation.
AB  - To study the differentiation process of erythroid progenitors from normal human
      bone marrow and peripheral blood, CD34/CD36 sorted cells were cultured in the
      presence of Erythropoietin (Epo) and Epo plus mast cell growth factor (MGF). The
      CD34+/CD36- cell fraction from bone marrow supported 74 +/- 33 erythroid burst
      forming units (BFU-E)/10(4) cells (mean +/- SD, n = 4) in the presence of Epo,
      which increased 2.1-fold by coculturing with MGF. However, erythroid colony
      forming units (CFU-E) were not cultured from the CD34+/CD36- cell fraction. In
      contrast, the CD34-/CD36+ cell fraction supported CFU-Es in the presence of Epo
      (152 +/- 115/10(5)) or Epo plus MGF (180 +/- 112/10(5)), whereas BFU-Es were
      hardly noticed. However, the transition of the BFu-E to CFU-E was observed by
      incubating CD34+/CD36- cells (10(4)/100 microL) in suspension with Epo plus MGF
      for 7 days followed by Epo in the colony assay. This was reflected by the
      appearance of CD34-/CD36+/Glycophorin A+/CD14- cells. In addition high numbers of
      CFU-Es (1,000 +/- 150, n = 4) were cultured from this cell fraction. In contrast
      to bone marrow erythroid progenitors, no peripheral blood CFU-Es were cultured
      from either the CD36+ or CD36- fraction, whereas BFU-Es were predominantly
      present in the CD36+ fraction. However, the CD34+ progenitor cell from peripheral
      blood did have intrinsic capacity to differentiate to CFU-Es because CD34+/CD36-
      cells incubated with Epo plus MGF for 7 days and followed by Epo in the colony
      assay, supported high numbers of CFU-Es (1,200 +/- 400, n = 3). To study whether
      additional growth factors have similar effects on erythroid progenitors,
      experiments were performed with interleukin 1 (IL-1), IL-3, and IL-6. IL-1 and IL
      6 did not modulate the Epo supported proliferation and differentiation. In
      contrast, IL-3 in the presence of Epo did support CFU-Es, from CD34+/CD36- cells
      after 7 days in suspension culture. However, flow cytometry analysis showed that
      Epo plus IL-3 not only supported CD34-/CD36+/Glycophorin A+ cells but also
      CD36+/CD14+ cells, indicating the differentiation along different cell lineages.
      In summary, the data show a phenotypic distinction between bone marrow and
      peripheral blood erythroid progenitors with regard to CD36 expression. In
      addition, the results suggest that Epo plus MGF or IL-3 and preincubation in
      suspension culture are prerequisites for the transition of the BFU-E to the CFU
      E.

PMID- 7517220
TI  - The nature of the B lymphocyte in B-chronic lymphocytic leukemia.
AB  - We have analyzed phenotypic, functional, and molecular properties of B-chronic
      lymphocytic leukemia (B-CLL) cells as compared to normal B cell differentiation
      stages and/or subsets. The possibility that the target B cell population
      transformed by the I primary oncogenic event(s) belongs to the normal CD5+ B cell
      subset from B mantle zone of secondary follicles is highly likely on phenotypic
      grounds. Though the genes responsible for the primary oncogenic event are
      presently unknown, a number of functional and molecular findings indicate that
      the end-product of their transforming activity is a cell frozen in the G0 phase
      of the cell cycle. This cell has several abnormalities that prevent an
      appropriate mitogenic response and presents a pattern of apoptosis-related gene
      expression that hinders apoptotic death. Pivotal to this apoptosis-escaping
      capacity is the expression of Bcl-2. We suggest that the increased expression of
      Bcl-2 together with an asynchronism between the expression of Bcl-2, c-myc, and
      APO1/Fas gene products shift the cellular balance away from apoptosis thereby
      helping the progressive accumulation in G0 of malignant CD5+ B cells.

PMID- 7517221
TI  - Tumor angiogenesis in node-negative breast carcinomas--relationship with
      epidermal growth factor receptor, estrogen receptor, and survival.
AB  - Angiogenesis is essential for tumor growth and metastases. Studies in breast
      carcinomas suggest that microvessel quantitation as a measure of angiogenesis
      might be one of the most powerful prognostic tools available. Node negative
      breast cancer is a particular group for which better prognostic markers would be
      helpful. We therefore measured microvessel density in a series of well
      characterised node negative breast carcinomas to evaluate angiogenesis as a
      prognostic marker and assess its relationship to epidermal growth factor receptor
      (EGFR) and estrogen receptor (ER), which have previously been reported to be of
      value. 109 patients with a mean age of 55 years and a median follow-up of 25
      months were examined. Vessels were immunohistochemically highlighted using an
      antibody to platelet endothelial cell adhesion molecule CD31, and microvessel
      density was quantified using a Chalkley point eyepiece graticule. No significant
      correlation was observed with patient age, tumor size, grade, ER, or EGFR
      expression. In a univariate analysis of survival, whereas ER expression was not a
      significant indicator of either relapse-free (RFS) or overall survival (OS),
      vascular count (VC) predicted both early RFS and OS (p = 0.01) and p = 0.028
      respectively). Furthermore, in patients with ER positive tumors, a subgroup
      usually considered to have a good prognosis, there was a significant reduction in
      RFS and OS if tumors had high VCs (p = 0.05 and p = 0.002 respectively). A
      further statistically significant reduction in RFS (p = 0.05) was observed for
      EGFR positive highly vascular tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517222
TI  - Determination of epidermal growth factor receptor provides additional prognostic
      information to measuring tumor angiogenesis in breast carcinoma patients.
AB  - Recent studies have shown that women with invasive breast carcinoma having high
      microvessel density (MVD) (a measure of tumor angiogenesis) or epidermal growth
      factor receptor (EGFR) expression have increased risk for metastasis and/or
      decreased survival. To determine if MVD and EGFR expression provide additive
      prognostic information, we analyzed these two prognostic indicators in the
      primary invasive breast carcinomas from 165 consecutive patients, who were
      followed for a median of 51 months. Univariate analysis showed a highly
      significant (p < 0.001) association of MVD with overall and relapse-free survival
      in all patients, including both node-negative and node-positive groups (see JNCI
      84:1875-1887, 1992). For EGFR, although univariate analysis suggested that women
      with tumors showing EGFR expression relapsed earlier and, perhaps, died earlier,
      the differences were not statistically significant. Multivariate analysis, in
      contrast, revealed that determination of EGFR did provide significant additional
      information to that already provided by MVD for predicting relapse-free survival
      in all women (p = 0.001) and in the subset of node-positive women (p = 0.007).
      Among node-negative women, however, the contribution of EGFR expression in
      predicting relapse-free survival was not significant (p = 0.12). Likewise, EGFR
      measurement did not provide significant additional information beyond that of MVD
      alone for predicting overall survival. Thus, EGFR provides additional prognostic
      information to determination of MVD, but only for relapse-free survival in node
      positive women with invasive breast carcinoma.

PMID- 7517223
TI  - Apoptosis in human skin development: morphogenesis, periderm, and stem cells.
AB  - During human skin development, embryonic- and fetal-specific periderm cells and
      incompletely keratinized cells are replaced by keratinocytes that differentiate
      while stratifying to form the fully functional epidermis. Proliferating basal
      cells of fetal skin also develop into epidermal appendages such as hair follicles
      and glands. We demonstrate that programmed cell death, not emphasized in
      conventional epidermal biology, has an important function in establishing the
      final architecture of the human epidermis and its appendages. Immunohistochemical
      localization of transglutaminases in fetal periderm, intermediate epidermal
      cells, and within appendages coincides with DNA fragmentation indicating that
      apoptosis is involved in deletion of these stage-specific cells and remodeling of
      appendages. The data also suggest that terminal differentiation of epidermal
      cells might be a specialized form of apoptosis. The pattern of expression of bcl
      2, a gene associated with survival of some cells, is exclusive of the
      distribution patterns of markers of the cell death pathway. Bcl-2 protein is
      correlated with specific morphogenetic events in hair follicles and eccrine sweat
      glands, and its presence in single cells of the hair follicle bulge suggests that
      Bcl-2 may be a stem cell marker.

PMID- 7517225
TI  - Markers for pancreatic allograft rejection: comparison of serum anodal
      trypsinogen, serum amylase, serum creatinine and urinary amylase.
AB  - Currently, the markers of acute rejection in pancreas allografts are not
      consistently reliable. The purpose of this study was to evaluate the ability of
      sAT to predict acute rejection as compared to serum creatinine (sCr), urinary
      amylase (uAmy) and serum amylase (sAmy). Eleven first-time acute rejection
      episodes in bladder-drained SPK recipients were studied. All rejection episodes
      were biopsy-proven (core kidney 9, fine needle kidney 2, fine needle pancreas 5).
      Sera obtained from days -7 to -1 (pre-treatment), day 0 (start of anti-rejection
      treatment), and +1 to +7 (post-treatment) periods were analyzed. Peak median sAT
      and sAmy levels occurred at day 0 compared to day 1 for sCr. uAmy trough levels
      occurred on days -4, -5 and +2. The difference between pre-treatment levels and
      those on day 0 were significant for sAT, sAmy and sCr but not for uAmy. Only in
      the case of sAT was the difference between day 0 levels and post-treatment levels
      significant. Both sAmy (0.87) and sCr (0.85) demonstrated positive correlation
      when compared to sAT whereas uAmy demonstrated a weak negative correlation (
      0.24). This study confirms that sAT accurately predicts rejection after SPK
      transplantation.

PMID- 7517224
TI  - Deficient outgrowth of the ureteric bud underlies the renal agenesis phenotype in
      mice manifesting the limb deformity (ld) mutation.
AB  - Mice which are homozygous for the limb deformity (ld) mutation also manifest an
      incompletely penetrant unilateral or bilateral renal agenesis phenotype.
      Intercross experiments suggest that the differences in penetrance of the renal
      agenesis phenotype between homozygous mice with different ld alleles are due to
      intrinsic differences in the strength of the mutant alleles or to one or more
      closely linked modifying loci, and not to generalized differences in genetic
      background. Analysis of ld/ld embryos between embryonic days 11-13 reveals
      delayed outgrowth or complete absence of the ureteric bud, the inducer of
      metanephric mesenchyme. Since explants of ld/ld metanephric mesenchyme
      differentiate in culture when apposed to embryonic spinal cord, we conclude that
      deficient ureteric bud outgrowth is the morphologic basis for renal agenesis in
      ld/ld mice. However, since ld transcripts can be detected in both metanephric
      mesenchyme and ureteric bud, the molecular basis for the deficiency in ureteric
      bud outgrowth could reside in either component.

PMID- 7517226
TI  - FK 506: an update.
AB  - A metabolite of the fungus Streptomyces tsukubaensis was isolated in 1984. It was
      given the investigative code name FK 506 and was found to have potent
      immunosuppressive effects in vitro and vivo. In 1989 the first human trials were
      begun in Pittsburgh. Based on the positive findings of those trials two large
      multicenter trials were started, one in the United States and one in Europe. In
      the U.S. trial the study group was treated with FK 506 and corticosteroids at
      half the dose of the control group. The control group was treated with
      cyclosporine, azathioprine and corticosteroids. The protocol design grew out of
      the observations and concerns raised at the early trial in Pittsburgh. The 1-year
      patient survival was 80% in both groups, and the graft survival was 82% in FK 506
      and 79% in the control group (NS). However, at the end of the 1st year 32% of the
      study group had not had any rejections vs 24% of the control group (p < 0.002).
      This was accentuated in the pediatric patients, of whom 58% of the FK 506-treated
      patients were free of rejections vs 28% of the control group at 6 months. The
      incidence of OKT3 treatment for steroid-resistant rejection was significantly
      lower (16%) in the FK 506 group compared to the control group (29%); p = 0.0001.
      The main adverse experiences were renal and neurotoxicity which were more common
      in the FK 506 patients than in the control group. FK 506 has been used
      extensively for rescue of treatment-resistant rejections. Unfortunately, no such
      trials have been randomized.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517227
TI  - Syntheses and antibacterial activities of gramicidin S analogs containing L
      ornithine in place of L-valine.
AB  - A gramicidin S analog ([Orn1,1']GS.4HCl) containing L-ornithine in place of L
      valine at the 1,1' positions was synthesized by the conventional solution method
      in order to examine whether this analog had antibacterial activity toward Gram
      negative bacteria. In the synthesis of [Orn1,1']GS.4HCl, two intermediate analogs
      ([Orn1,1', Orn(For)2,2']GS.2HCl and [Orn(Z)1,1']GS.2HCl) were obtained.
      [Orn1,1']GS.4HCl and [Orn1,1', Orn(For)2,2']GS.2HCl showed no activity toward
      either Gram-negative or Gram-positive bacteria, whereas [Orn(Z)1,1']GS.2HCl
      showed appreciable activity toward only Gram-positive bacteria.

PMID- 7517229
TI  - Long-term survival in a patient with malignant carcinoid treated with high-dose
      octreotide.
AB  - Octreotide acetate, a long-acting somatostatin analogue, is effective in
      controlling and markedly reducing the symptoms of carcinoid crisis. We report a
      patient with carcinoid syndrome with prolonged survival for 4.5 years with high
      dose octreotide therapy and survived for 7.5 years after the first flushing, in
      spite of episodes of severe carcinoid crisis. Dose escalation was required in
      order to control carcinoid symptoms, and the final dosage was 5,950
      micrograms/day. Although administration of such a high dosage of octreotide has
      never been reported before, we found that octreotide could be used at this dosage
      safely without inducing serious side effects, and probably prolonged the
      patient's survival. Our experience with this case indicates that octreotide
      acetate is an effective drug in controlling carcinoid crisis and prolonging
      survival without serious side effects.

PMID- 7517228
TI  - Hemagglutination activity of Lactobacillus acidophilus group lactic acid
      bacteria.
AB  - The cells of 28 strains of the Lactobacillus acidophilus group were evaluated for
      hemagglutination (HA) activity. The activity was found in the surface layer (SL)
      protein fraction extracted by 2 M guanidine hydrochloride. The most SL proteins
      from the A group strains (L. acidophilus (A1), L. crispatus (A2), L. amylovorus
      (A3), and L. gallinarum (A4)) showed HA activity, but the proteins from the B
      group strains (L. gasseri (B1) and L. johnsonii (B2)) showed no activity. The SL
      proteins from the A group strains were composed in common of a main component
      having molecular mass of about 40-45 kDa on SDS-PAGE. The SL proteins from JCM
      1034 strain that showed the highest HA activity was fractionated by CM-Toyopearl
      ion-exchange chromatography. The highest HA activity was detected in the major
      protein of 41 kDa. This protein was purified and shown to be composed of about
      50% of hydrophobic amino acids. The HA activity of the protein (1034 lectin) was
      specifically inhibited by fetuin and bovine lactoferrin at the concentrations of
      80 and 160 micrograms/ml, respectively. The removal of N-acetylneuraminic acid
      from fetuin significantly decreased the inhibitory activity.

PMID- 7517230
TI  - Capillary leak syndrome likely the result of granulocyte colony-stimulating
      factor after high-dose chemotherapy.
AB  - Two cases of malignant lymphoma complicated with capillary leak syndrome
      following super high-dose chemotherapy and administration of granulocyte colony
      stimulating factor (G-CSF) are presented. Subsequent to the nadir of
      granulocytes, and at the stage of rapid increase of granulocytes, the symptoms of
      fever, hypotension, dyspnea, pleural effusion and edema appeared, and laboratory
      data revealed hypoxia, hypocapnia and hypoalbuminemia. In addition, an abscess
      like lesion was observed in the liver in one patient. After the administration of
      G-CSF was ceased or decreased, and pulse therapy with methylprednisolone was
      initiated, these symptoms disappeared quickly.

PMID- 7517231
TI  - Peptides for inducing cross-reactive anti-malarial antibodies.
AB  - Immunological cross-reactions between malarial proteins are frequently observed.
      This paper describes an approach to generate such antibody responses that target
      many parasite proteins using a limited number of peptides as immunogens. Peptides
      used contained a known epitope, NKND, that is common to many malarial proteins or
      combinations of tri-peptides which are commonly present in parasite proteins. One
      of the two NKND-containing peptides elicited antibodies reacting to six parasite
      proteins and fusion proteins containing NKND. The antibody specificity was
      directed to NKND. Two of the four combination peptides were recognized by
      hyperimmune human sera and mouse immune serum in vitro, and one elicited
      antibodies recognizing parasites on immunofluorescence assay.

PMID- 7517232
TI  - The influence of water-miscible alcohols on the conformation of antibodies
      directed against a defined epitope.
AB  - Antiserum was raised against peptide P513 (CSQRSTNSAST) conjugated to diphtheria
      toxoid. P513 is a sequence derived from the Plasmodium falciparum merozoite
      surface antigen (MSA-2) containing the STNS epitope recognized by antibodies that
      inhibit parasite growth. Although antibodies directed against other STNS
      containing peptides can bind to the native MSA-2 antigen, polyclonal anti-P513
      serum failed to react in immunofluorescence assays with parasites or with MSA-2
      by Western blotting. However, addition of methanol, ethanol or 1-propanol
      modified the specificity of the anti-P513 interaction, resulting in recognition
      of MSA-2. The effect was concentration dependent: at high alcohol concentrations,
      the specificity was further modified, and a previously undescribed rhoptry
      antigen was recognized. These results indicate that addition of alcohols to
      immunoassays may provide a way of modifying the specificity of antibodies in
      general, and the reactivity of anti-peptide serum with the parent protein in
      particular.

PMID- 7517233
TI  - HCH residues in rain water from Hardwar, India.

PMID- 7517234
TI  - Morphogenesis of Dictyostelium discoideum treated with lindane.

PMID- 7517235
TI  - Interaction of lindane and carbaryl on hepatic microsomal enzymes in rats.

PMID- 7517237
TI  - [Is blockade of histamine receptors before protamine administration of value?].

PMID- 7517236
TI  - Sequential observation of mitochondrial distribution in mouse oocytes and
      embryos.
AB  - OBJECTIVE: The purpose of this study was to elucidate changes in the distribution
      of mitochondria through the cell cycle. MATERIALS AND METHODS: Mouse oocytes and
      embryos were recovered sequentially from mice and stained with the vital
      fluorescent mitochondrial stain rhodamine 123. Mitochondrial staining pattern
      were classified into three types: aggregation (Ag), homogeneous (H), and
      perinuclear accumulation (PA). RESULTS: Sequential observations revealed that
      mitochondria of oocytes and embryos grown in vivo translocated in the cytoplasm
      during the cell cycle, showing the H pattern before human chorionic gonadotropin
      (hCG) administration, the PA pattern 8-9 hr post-hCG, the H pattern again 10-14
      hr post-hCG, and the PA pattern again 24 and 31-32 hr post-hCG following
      fertilization. In the two-cell stage, the Ag pattern was shown 35 hr post-hCG,
      the H pattern was observed 40 hr post-hCG, and the PA pattern was found 48 hr
      post-hCG. In the embryos cultured in vitro and showing developmental block,
      mitochondrial translocation was shown to be inhibited after they aggregated in
      the early two-cell stage (35 hr post-hCG). Moreover, the translocation of
      mitochondria was restored by the addition of superoxide dismutase or thioredoxin
      to the culture medium. Both of these enzymes have already been shown to have the
      ability to overcome developmental block. CONCLUSION: The present study revealed
      that mitochondria translocated in the cell cycle and suggested that there is a
      close relationship between mitochondrial translocation and developmental arrest.

PMID- 7517238
TI  - [Effectiveness of preventing hypotension with H1/H2 antagonists before protamine
      administration].
AB  - BACKGROUND: This prospective randomized study was undertaken to evaluate the
      effects of prophylactic administration of H1/H2 receptor blockers on histamine
      release and hemodynamic changes after administration of protamine in two groups
      of patients (n = 20) undergoing elective coronary artery bypass graft surgery.
      PATIENTS AND METHODS: Group 1 (n = 10) patients were pretreated intravenously
      with 1 mg/kg ranitidine and 0.1 mg/kg dimetinden 15 min before termination of the
      extracorporeal circulation; group 2 patients (n = 10) received no medication.
      After termination of the extracorporeal circulation, heparin was neutralized by
      administration of 350 U/kg protamine, injected during 4 min via a peripheral
      vein. Hemodynamic measurements were carried out before the administration of
      protamine and at 1-min intervals up to 10 min after the injection. Before
      administration of protamine and 2, 4, 6, 8, and 10 min thereafter, plasma
      histamine levels were measured using central venous blood samples. RESULTS: In
      group 1 patients, who were treated prophylactically with H1/H2 receptor blockers,
      the plasma histamine concentration was 0.21 +/- 0.15 ng/ml (mean +/- SD) and
      reached a peak value of 0.30 +/- 0.17 ng/ml within 4 min. In group 2 patients,
      the plasma histamine concentration increased from 0.17 +/- 0.15 to 0.26 +/- 0.24
      ng/ml after 10 min. The hemodynamic reactions were comparable in both groups
      (group 1: decrease in systolic arterial pressure from 118 +/- 16 to 104 +/- 15 mm
      Hg; group 2: from 111 +/- 19 to 108 +/- 21 mm Hg; differences statistically not
      significant). The Spearman rank correlation revealed no statistically significant
      relationship between the slight plasma histamine release and clinically severe
      decreases of blood pressure that were observed in single patients. CONCLUSION:
      Histamine release appears unlikely as the mechanism of protamine-induced
      hypotension. Therefore, general prophylaxis using H1/H2 receptor antagonists does
      not seem to be justified and cannot be recommended.

PMID- 7517239
TI  - [Autotransfusion with leap-frog technique in patients with coronary heart disease
      and planned aortocoronary venous bypass].
AB  - OBJECTIVE: The goal of the study is to test and control the quality of a special
      leap-frog technique which enables saving heterologous blood. DESIGN: In a
      randomized double-blind placebo-controlled study homologous blood was taken in 40
      out of 100 patients with coronary heart disease before aortocoronary bypass
      operation. The leap-frog technique was used. Within 8 weeks 3-4 erythrocyte
      concentrates and 0.9-1.2 liters plasma were sampled. The volume (verum: HES
      200/0.5 10%; placebo: 0.9% NaCl solution) substituted corresponding to the volume
      of blood donated. Each patient received 200 mg Fe2+/day p.o. RESULTS: Clinically,
      only patients treated with HES in stage of autologous blood sampling benefited
      significantly. Two patients showed adverse effects. The peri- and postoperative
      course was comparable. In the NaCl group one of the patients received homologous
      erythrocyte concentrates. None of the patients died pre-, peri- or post
      operatively. CONCLUSIONS: 40% of the cardiosurgical patients could be considered
      for autologous blood donation. Isovolemic hemodilution with HES 200/0.5 10% was a
      suitable and safe measure in preoperative blood sampling. Physical exercise
      should be performed before and after autologous blood donation. A reduced
      exercise tolerance suggests that autologous blood donation should be stopped.

PMID- 7517241
TI  - Stereospecific assignments of glycine in proteins by stereospecific deuteration
      and 15N labeling.
AB  - A method is described for stereospecifically assigning the alpha-protons of
      glycine residues in proteins. The approach involves the stereospecific
      deuteration and 15N labeling of glycine and subsequent selective incorporation of
      this residue into the protein. The stereospecific assignments of the glycine
      alpha-protons are obtained from a comparison of a 3D 15N-resolved TOCSY spectrum
      of the uniformly 15N-labeled protein with a 2D/3D 15N-edited TOCSY spectrum of
      the protein, containing the stereospecifically deuterated and 15N-labeled
      glycine. The approach is demonstrated by stereospecifically assigning the glycine
      alpha-protons of the FK506 binding protein when bound to the immunosuppressant
      ascomycin.

PMID- 7517242
TI  - Sequence-dependent conformational heterogeneity of a hybrid DNA.RNA dodecamer
      duplex.
AB  - Two- and three-dimensional homonuclear NMR studies of a hybrid duplex RI, formed
      by annealing r(GCGCAAAACGCG) and d(CGCGTTTTGCGC) strands are described. NMR
      parameters, such as intra- and interresidue proton-proton NOEs and sugar proton
      coupling constants were analyzed with reference to those of the corresponding
      DNA.DNA duplex. Furthermore, spectral analyses were conducted on the basis of
      model structures of nucleic acid duplexes. Distinctive spectral patterns of the
      hybrid duplex reveal unique heterogeneous conformations which co-exist throughout
      the sequence and are significantly different from those of model structures of
      either canonical A- or B-forms. Features of an intermediate conformation were
      observed in the DNA and RNA strands in duplex RI, the former being more B-like
      and the latter more A-like. Three-dimensional NOESY-NOESY spectra were analyzed
      and their use was demonstrated for resolving superimposed resonances and cross
      peaks, especially those originating from the RNA strand. The application of a
      useful strategy that combines the use of 2D NMR data and the known structural
      information for efficient 3D spectral analyses is demonstrated.

PMID- 7517240
TI  - On the role of AP2 in epithelial-specific gene expression.
AB  - Transcription factor AP2 plays an important role in transcription of keratin
      genes, and it has been suggested that AP2 confers epithelial specificity.
      Promoters of keratin genes contain AP2 sites, usually within tight clusters of
      binding sites for other nuclear transcription factors. The role of AP2 was
      examined by in vitro gel shift analysis, AP2 binding site mutagenesis, and stable
      and transient transfection experiments. Nonepithelial cells, such as GM10
      fibroblasts and melanocytes, neither express keratin nor become phenotypically
      epithelial when transfected with an AP2-expressing vector. However, in 3T3 and
      HeLa cells, co-transfection of an AP2-expressing vector increases the level of
      transcription from keratin gene promoters. This increase requires an intact AP2
      binding site. Thus, the role of AP2 in keratin gene expression is quantitative
      rather than qualitative. AP2 interacts with other transcription factors and may
      convey extracellular regulatory signals to the transcription complex in the
      promoters of keratin genes.

PMID- 7517244
TI  - Homeopathic remedies: scepticism abounds.

PMID- 7517245
TI  - Infantile endodermal sinus tumor presenting with vaginal bleeding: report of a
      case.
AB  - Endodermal sinus tumor (EST) of the vagina is extremely rare and primarily
      affects infants. We report on a six-month-old female infant with EST of the
      vagina who presented with vaginal spotting of one month's duration. Pelvic
      ultrasound and computerized tomography showed a 3.8 x 3.5 cm heterogeneous mass
      between the bladder and the rectum. The serum alpha-fetoprotein (AFP) level was
      high (1270 ng/mL) and the beta-human chorionic gonadotropin was undetectable. She
      received surgical intervention followed by chemotherapy. The patient was disease
      free and serum AFP remained undetectable during the eight-month follow-up period.

PMID- 7517243
TI  - [Prostaglandin instillation versus tubotomy. Results of a prospective study].

PMID- 7517246
TI  - Risperidone for schizophrenia.

PMID- 7517247
TI  - Palliative care.
AB  - Though many of the treatment strategies used in palliative care have never been
      subjected to clinical trial, it has been argued that advances in palliative care
      have outstripped those in many other specialties. This article is not a
      comprehensive review of therapeutic options, nor even of recent advances in this
      topic, but concentrates on the latest developments and controversies in the
      pharmacological treatment of four frequent and important symptoms: neuropathic
      pain, anorexia and cachexia, intestinal obstruction, and breathlessness. It is
      difficult to perform blinded, randomised trials in patients with advanced disease
      and poor performance status, yet it is these patients who may gain most from the
      adoption of new well evaluated treatment strategies.

PMID- 7517248
TI  - Cancer of the upper gastrointestinal tract. Palliative chemotherapy unproved in
      advanced gastric cancer.

PMID- 7517249
TI  - Synthesis of heat shock proteins in Thermoanaerobacterium thermosulfurigenes EM1
      (Clostridium thermosulfurogenes EM1).
AB  - The response to heat stress was examined in Thermoanaerobacterium
      thermosulfurigenes EM1. Upon a temperature shift-up from 50 degrees to 62 degrees
      C, four heat shock proteins (hsps) were synthesized at an elevated level. Two
      proteins were found to be immunologically related to the Escherichia coli GroEL
      protein and the Mycobacterium tuberculosis hsp71 (DnaK similar protein), and the
      corresponding groE and dnaK homologous sequences were detected in the chromosome
      of T. thermosulfurigenes EM1. The heat shock response in this thermophile was
      transient, with a maximum synthesis of hsps between 10 and 15 min after the
      shock. The enhanced synthesis of DnaK and GroEL was consistent with increased
      mRNA levels of the genes, which reached a maximum 15 min after heat treatment.

PMID- 7517250
TI  - Worldwide patterns of cancer mortality, 1985-89.
AB  - Histograms of all age-standardized death certification rates from 26 cancers or
      groups of cancers and total cancer mortality for the most recent calendar
      quinquennium (generally 1985-89) were produced for 55 countries: 26 in Europe,
      the former Soviet Union (USSR), three in North America, 13 in Latin America and
      the Caribbean, two in Africa, eight in Asia and two in Oceania, providing
      interpretable data to the World Health Organization database. Major differences
      were observed for all common cancer sites, including stomach (49/100,000 males in
      Costa Rica, 38 in the USSR and Japan vs 5/100,000 in the United States),
      intestines (over 25/100,000 males in Czechoslovakia, Hungary and New Zealand vs
      10-15/100,000 in Japan and Southern Europe and less than 5/100,000 in most Latin
      American and Asian countries), lung (over 70/100,000 in Belgium, Scotland, The
      Netherlands, Czechoslovakia and Hungary, and less than 20/100,000 in most Latin
      American and Asian countries; over 20/100,000 females in Britain, Hong Kong, the
      United States and Denmark vs less than 5/100,000 in France, Spain and again most
      areas of Asia and Africa providing data; breast (over 25/100,000 females in Great
      Britain, New Zealand, Belgium, The Netherlands and Uruguay, vs less than
      10/100,000 in Japan, Hong Kong and most Latin American countries). Thus, there
      was over a fivefold variation in total cancer mortality for both sexes, the
      highest rates being in Hungary (237/100,000) and Czechoslovakia (229/100,000) for
      males, and in Denmark (142/100,000) and Scotland (138/100,000) for females.
      Although problems of validity and reliability of cancer death certification,
      mostly in developing countries, may in part explain this variation, these
      substantial differences are at least in part real and essentially reflect,
      besides the impact of breast cancer in females and of stomach and colorectal
      cancer in both sexes, the different spectrum of the tobacco-related lung cancer
      epidemic in the two sexes and in various areas of the world.

PMID- 7517251
TI  - Evaluation of CYFRA 21-1 as a new marker for non-small cell lung cancer.
AB  - The levels of the new tumour marker CYFRA 21-1 were assessed in 115 patients with
      non-small cell lung cancer (NSCLC) and in 45 patients with non-malignant lung
      disease. Increased levels of CYFRA 21-1 were observed in 47.8%, mostly in
      patients with squamous cell carcinoma (SCC; 69.1%). Serum CYFRA 21-1 levels were
      correlated with the stage of SCC type. Positive CYFRA 21-1 levels in patients
      with SCC were present in 40% of stage I, 61.1% of stage II, and 85.2% of stage
      III. In addition, SCC patients who presented mediastinal lymph nodes (N2)
      demonstrated higher serum CYFRA 21-1 levels, compared with patients without
      mediastinal lymph nodes metastases (N0 or N1). With regard to tumour size,
      significant difference was observed between T1, T2 and T3. The study also showed
      that the percentage of patients who survived 18 months with normal preoperative
      level of CYFRA 21-1 was higher compared with those patients with elevated
      preoperative levels of this marker, but the differences were not statistically
      significant.

PMID- 7517252
TI  - The variant mRNA isoform of human metastasis gene (CD44V) detected in the cell
      lines of human hepatocellular carcinoma.
AB  - The interaction of the cell surface receptor CD44 molecular with its ligands
      (addressin, extracellular matrix etc.,) plays an important role in fulfilling the
      lymphocyte homing and immune reaction. Recently alternatively spliced products of
      CD44 gene are found to be involved in tumor metastasis as well. Our report found
      that CD44 prototype RNA (CD44S) was present in all five tumor cell lines. Isoform
      CD44 RNA (CD44V) was recognized in three metastasized hepatocellular carcinoma
      cell lines, J5, HCC36, HEP3B. In addition, the J5 CD44 RNA isoform expressed two
      distinct transcripts which are of the same size as MDA-231 breast tumor cell
      line. The MDA-231 CD44 RNA variant (CD44V) has been confirmed to contain
      metastasis domain 4 and 5. It is implicated that the alternative RNA splicing may
      also play a major role in hepatocellular carcinoma metastasis.

PMID- 7517253
TI  - The water channel gene in human uterus.
AB  - The cDNA coding the water channel was isolated from a human uterus cDNA library
      template by a one-step polymerase chain reaction (PCR). The oligonucleotide
      primers corresponding to the 5' untranslated nucleotide sequence and
      complementary to the 3' untranslated nucleotide sequence of the cDNA coding the
      28 kDa erythrocyte integral membrane protein (CHIP28) were synthesized and used
      to initiate the reaction. A 1340 bp cDNA coding the human uterine water channel
      (hUWC) was cloned and sequenced. The hUWC showed 99.8% and 99% identity with the
      nucleotide and amino-acid sequences of CHIP28, respectively. The deduced hUWC
      polypeptide is composed of 269 amino acid residues with a single amino acid
      variant from CHIP28 protein at position 45, where valine replaces alanine. The
      hUWC cDNA translated in a prokaryotic protein expression system produced a
      protein with an estimated Mr of 28 kDa, equivalent to the size of the human red
      cell CHIP28 protein. The present results suggest that the human uterus contains
      water channels that may play an important role in regulating water transport and
      imbibition in the uterus.

PMID- 7517257
TI  - Peripheral blood stem cells for allogeneic transplantation.

PMID- 7517255
TI  - Peripheral blood progenitors mobilised by G-CSF (filgrastim) and reinfused as
      unprocessed autologous whole blood shorten the pancytopenic period following high
      dose melphalan in multiple myeloma.
AB  - Growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) is
      effective at progenitor release into the peripheral blood. After high-dose
      chemotherapy haematopoietic reconstitution occurs after reinfusion of these
      peripheral blood progenitor cells (PBPC). However, the collection by
      leukapheresis and further processing of PBPC are very time consuming and
      expensive. We have studied the transplantation potential of a small volume of
      unprocessed autologous whole blood after G-CSF mobilisation. Six patients with
      plasma cell disorders received G-CSF 10 micrograms/kg sc during 6 days.
      Subsequently 11 of whole blood was collected by phlebotomy, kept unprocessed at
      room temperature and reinfused 24 h after high-dose melphalan 140 mg/m2. CFU-GM
      content was 845 per ml blood (median, range 320-3472) and CD34+ cells rose to a
      median percentage of 0.9 (range 0.4-2.0). Haematological recovery was
      significantly faster in the study group compared with the control group of 20
      patients who received the same dose of melphalan without reinfusion of PBPC. The
      neutrophil count reached 0.5 x 10(9)/l at a median of 12.5 days after infusion of
      PBPC vs 38 days in the control group (p = 0.0003). The platelet count reached 20
      x 10(9)/l after a median of 23.5 days vs 38 days (p = 0.0218). The shortened
      recovery was reflected by less transfusions, less antibiotic use and shortening
      of hospital stay (19 days vs 43 days, p = 0.0003). We conclude that this easy
      technique of mobilisation and collection of PBPC is very effective for hastening
      haematologic recovery after high-dose chemotherapy.

PMID- 7517254
TI  - Comparison of the effects of CD3 and CD5 donor T cell depletion on graft-versus
      leukemia in a murine model for MHC-matched unrelated-donor transplantation.
AB  - Studies were designed to prospectively evaluate the effects of selective
      depletion for donor T cells strongly expressing the CD3 and CD5 pan-T antigens on
      the incidence of leukemia relapse following bone marrow transplantation. This
      evaluation was performed under controlled conditions in a mouse model for MHC
      matched unrelated-donor transplantation, employing Rauscher leukemic SJL/J mice
      as the recipients and leukemia-resistant B10.S mice as the donors. Selective
      donor cell depletion for CD3 and CD5 was accomplished ex vivo prior to
      transplantation by incubation with the appropriate monoclonal antibody plus
      complement. When untreated, Rauscher leukemia resulted in a 97% fatality
      incidence. This was reduced to 30% by the transplant of non-depleted B10.S cells,
      with another 37% recipients dying from GVHD and graft failure. CD3 depletion
      reduced the GVHd deaths to 6% but increased relapse to 62%. Conversely, CD5
      depletion had no effect on relapse or on GVHD but did significantly increase
      graft failure, thus negatively affecting survival. Evaluation of the results,
      done in conjunction with flow cytometry analysis of the effects of CD3 versus CD5
      depletion on the donor cells, suggests that the T cells involved in suppressing
      leukemic relapse in these studies, and hence contributing to the GVL response,
      most probably had a phenotype of CD3+, CD5-.

PMID- 7517256
TI  - Controlled trial of orally administered immunoglobulin following bone marrow
      transplantation.
AB  - Between May 1987 and September 1989, 72 patients undergoing marrow
      transplantation at a single institution were randomized to receive 50 mg/kg of a
      commercial gammaglobulin preparation or placebo daily in four divided doses for
      28 days following transplantation. Patients receiving oral gammaglobulin had
      significantly increased concentrations of stool IgG (p = 0.01) compared with the
      placebo group. There was no difference in the amount of diarrhea, frequency of
      GVHD, duration of hospitalization or survival in the two groups. The present
      study demonstrates that orally administered IgG can survive passage through the
      gastrointestinal tract of bone marrow transplantation recipients but there was no
      effect of oral administration of immunoglobulin on morbidity or mortality
      following bone marrow transplantation.

PMID- 7517258
TI  - Lymphocyte content in peripheral blood mononuclear cells collected after the
      administration of recombinant human granulocyte colony-stimulating factor.
AB  - The effects of rhG-CSF on peripheral blood lymphocytes and lymphocyte populations
      in the apheresis product has been determined in 13 individuals (11 autografts and
      2 normal donors) who had peripheral blood mononuclear cells (PBMCs) collected on
      days 3, 4, and 5 of administration of rhG-CSF 16 micrograms/kg/day x 5 days. The
      absolute number of CD34+ cells increased 9 and 25-fold from pretreatment levels
      after 4 and 5 days of rhG-CSF, respectively. All patients demonstrated an
      increase in CD3, CD4, CD8, CD19 and CD20 lymphocytes after 3 days of rhG-CSF with
      T lymphocytes increasing 1.5-2.0 times baseline by day 3 or rhG-CSF
      administration. All lymphocyte phenotypes returned to below pretreatment levels
      on days 4 and 5 of rhG-CSF administration. The ratio of CD4/CD8 lymphocytes was
      not affected by rhG-CSF. Collection of PBMCs on 3 consecutive days yielded a mean
      of 8.77 x 10(8) CD34 cells, 14.03 x 10(10) total nucleated cells and 3.17 x
      10(10) CD3 lymphocytes. These data suggest that rhG-CSF mobilized PBMCs have
      approximately one log more T cells than marrow and the effect of rhG-CSF on the
      quantity and phenotype of lymphocytes is minimal. Strategies for coping with an
      increased incidence of GVHD, if it occurs, could include the utilization of both
      methotrexate and cyclosporine as immunoprophylaxis, selective T cell depletion or
      CD34 positive selection.

PMID- 7517259
TI  - Positive selection of hematopoietic CD34+ stem cells provides 'indirect purging'
      of CD34- lymphoid cells and the purging efficiency is increased by anti-CD2 and
      anti-CD30 immunotoxins.
AB  - Human CD34+ hematopoietic cells were purified using the avidin-biotin
      immunoabsorption technique. The selected population showed 78.6 +/- 3% CD34+
      cells and the overall recovery of CD34+ cells, CFU-GM and BFU-E from the starting
      population was 34 +/- 5%, 71 +/- 4% and 67 +/- 2%, respectively. Hematopoietic
      progenitor cell purification also resulted in 3 log of normal T cell depletion
      from the bone marrow (BM) by immunofluorescence analysis. Moreover, when
      unseparated BM cells were mixed with the CD34- lymphoma cell lines D430B and
      Raji, the removal of greater than 3 log of tumor cells from the enriched CD34+
      cell fraction was demonstrated. To increase the neoplastic cell purging, several
      immunotoxins (IT) containing the ribosome-inactivating protein (RIP) saporin and
      directed toward the lymphoid-associated antigens CD30 and CD2 were prepared. Our
      experiments showed only a minimal toxicity of the immunoconjugates on colony
      forming cells (CFC) derived from purified CD34+ cells. Conversely, all the ITs
      were very effective in inhibiting protein synthesis and growth of normal and
      neoplastic lymphoid cells. Further experiments demonstrated that the sequential
      combination of CD34+ cells purification and IT treatment resulted in 5 or more
      log of tumor cell purging with no additional loss of BM progenitor cells.

PMID- 7517260
TI  - Correlation of colony-forming cells, long-term culture initiating cells and CD34+
      cells in apheresis products from patients mobilized for peripheral blood
      progenitors with different regimens.
AB  - Peripheral blood progenitor cell (PBPC) populations used for transplantation were
      analyzed for the presence of CD34+ cells, colony-forming cells (initial CFC), and
      long-term culture initiating cells (LTC-IC) cultured on irradiated stroma for 5
      weeks. Thirty-eight leukapheresis products were studied from 11 patients with
      breast cancer, 2 with non-Hodgkin's lymphoma and 1 with ovarian cancer harvested
      during recovery from either cyclophosphamide (CY) chemotherapy or
      cyclophosphamide-VP16 with G-CSF (CY-VP-G). CY-VP-G products had a threefold
      higher median number of mononuclear cells collected, a fivefold higher median
      concentration of CD34 and LTC-IC and a threefold higher concentration of initial
      CFC when compared with CY products. CY-VP-G products had a significantly higher
      ratio of CFU-GM to BFU-E than the CY-mobilized products. Significant correlations
      of r = 0.89 and r = 0.68 were observed when comparing CD34 and CFC in products
      from CY or CY-VP-G patients, respectively. Analysis of the regression lines
      indicated that slopes of these regression lines were significantly different with
      a ratio of CD34 to initial CFC of 15:1 in the CY-VP-G products versus 5.2:1 with
      the CY products. These data indicate a higher cloning efficiency of the CD34+
      population in the products from CY-mobilized patients. Significant correlations
      of r = 0.9 (CY) and r = 0.53 (CY-VP-G) were observed when the initial CD34
      concentration and the LTC-IC were compared. Comparison of initial CFC with LTC-IC
      also showed significant correlations (r = 0.94, CY; r = 0.58, CY-VP-G) in samples
      from both patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517262
TI  - General anesthesia and bone marrow harvesting procedure have no effect on the
      concentration of CD34 stem cells in peripheral venous blood.

PMID- 7517261
TI  - Clostridium septicum abscess in hepatic metastases: successful medical
      management.
AB  - Clostridium septicum bacteremia is frequently associated with hematologic and
      colonic malignancies and neutropenia. It frequently produces 'metastatic'
      gangrene with excessive mortality. Standard therapy usually includes surgical
      debridement and antibiotics. We present a patient with metastatic breast cancer
      treated with high-dose chemotherapy and bone marrow transplantation. She was
      treated successfully with antibiotics alone despite developing Cl. septicum
      bacteremia and gas in hepatic metastases. The pathophysiology of this infection
      is reviewed.

PMID- 7517263
TI  - Inhibitory effect of fatty acids on 8-hydroxydeoxyguanosine formation in calf
      thymus DNA treated with bleomycin-Fe(II).
AB  - The effect of fatty acids on 8-hydroxydeoxyguanosine (8-OH-dG) formation in calf
      thymus DNA treated with bleomycin (BLM)-Fe(II) in vitro was studied. The
      formation of 8-OH-dG was greatly reduced in the presence of stearic acid (18:0)
      or oleic acid (18:1), however, it increased to the control level with an increase
      in the number of unsaturated bonds of fatty acids (18:2, 18:3). This increase in
      8-OH-dG formation may have resulted from the indirect oxidation of DNA by the
      peroxidized unsaturated fatty acids formed by BLM-Fe(II). The inhibitory effect
      of saturated fatty acids on 8-OH-dG formation was observed with those possessing
      more than 12 methylene chains. Stearic acid also inhibited peroxidation of
      unsaturated fatty acids (18:2, 18:3) treated with BLM-Fe(II), however, it had no
      effect on ribose degradation of DNA treated with BLM-Fe(II). These results
      suggest that different active oxygen species are probably involved in DNA
      degradation and in formation of 8-OH-dG in DNA and of peroxidized products in
      fatty acids.

PMID- 7517264
TI  - Analysis of the CFTR gene in the Spanish population: SSCP-screening for 60 known
      mutations and identification of four new mutations (Q30X, A120T, 1812-1 G-->A,
      and 3667del4).
AB  - In order to determine the spectrum of CF mutations in the Spanish population, we
      have analysed 40 unrelated Spanish CF patients, with at least one chromosome
      negative for mutations delta F508, G542X, and N1303K. Exons 1-7,10
      14a,15,16,17b,18-21 of the CFTR gene were studied by Single Strand Conformation
      Polymorphism (SSCP) analysis, using 60 known CF mutations as controls. SSCP
      screening allowed us to detect 28 different mutations in 52 CF chromosomes, and
      to identify four new mutations (Q30X in exon 2, A120T in exon 4, 1812-1G-->A in
      intron 11 and and 3667del4 in exon 19). Further analysis of the four new
      mutations in a total of 950 Spanish CF chromosomes showed a final frequency of
      0.4%, 0.1%, 0.1%, and 0.1% for 1812-1G-->A,Q30X, A120T, and 3667del4,
      respectively. No mutations were detected in exons 1, 3, 14a, 16, and 18. We have
      also detected 10 intragenic polymorphisms and DNA sequence variants and have
      analysed their frequencies in our population. The total of 28 mutations
      identified in the 80 CF chromosomes highlight the molecular heterogeneity of CF
      in the Spanish population.

PMID- 7517265
TI  - Screening for CF mutations in adult cystic fibrosis patients with a directed and
      optimized SSCP strategy.
AB  - Twenty adolescent and adult cystic fibrosis (CF) patients have been studied for
      the presence of mutations in the CFTR gene. Mutations other than deltaF508 have
      been detected by comparison to the single-stranded conformation polymorphism
      (SSCP) pattern of known mutations in eight exons, in which 80% of the more common
      mutations are present. Each mutation was confirmed by direct sequencing. For each
      of the analyzed exons, optimal SSCP conditions have been determined that allow
      all available known mutations in that exon to be distinguished from each other.
      This approach allowed mutations to be defined in 75% of the non deltaF508 alleles
      and 92% of all CF alleles in this cohort.

PMID- 7517266
TI  - Hb FM-Fort Ripley: confirmation of autosomal dominant inheritance and diagnosis
      by PCR and direct nucleotide sequencing.
AB  - We describe a normal neonate who presented at four days of age with asymptomatic
      cyanosis. There was no evidence of cardiac or pulmonary abnormality and an
      extended family history included 13 other affected family members with
      asymptomatic cyanosis lasting one to three months. Polymerase chain reaction
      (PCR) amplification and direct nucleotide sequencing of the proband's G gamma
      chain gene revealed the mutation at codon 92 (CAC-->TAC) previously shown in
      haemoglobin FM-Fort Ripley (alpha 2 gamma G gamma 92 (F8) His-->Tyr). This is the
      first family with Hb FM-Fort Ripley reported so far. It demonstrates autosomal
      dominant inheritance of this condition and incomplete penetrance.

PMID- 7517268
TI  - Identification of four new mutations in the cystic fibrosis transmembrane
      conductance regulator gene: I148T, L1077P, Y1092X, 2183AA-->G.

PMID- 7517267
TI  - A cystic fibrosis patient with delta F508, G542X and a deletion at the D7S8
      locus.

PMID- 7517269
TI  - Structure and induction of a lysozyme gene from the tobacco hornworm, Manduca
      sexta.
AB  - Lysozyme is hypothesized to play a central role in initiating and maintaining the
      antibacterial defense response of Manduca sexta. We isolated a cDNA clone
      encoding a M. sexta lysozyme. Results of Northern blot analyses using this cDNA
      as a probe indicated that the abundance of lysozyme transcripts increased in
      seven tissues following treatment with peptidoglycan, with the highest level of
      accumulation occurring in the fat body. An analysis of the kinetics of
      accumulation of the transcripts in the fat body demonstrated low levels of
      transcripts in the naive larvae which increased rapidly after treatment and
      remained elevated over several days. A genomic fragment containing a lysozyme
      gene was also isolated and the nucleotide sequence and transcription start site
      of the gene was determined.

PMID- 7517271
TI  - Students with word finding disorders: three case studies.
AB  - Case studies of three students of different ages with different types and degrees
      of word finding disorders are presented. One student is at the beginning of his
      school career, one has been in school for 7 years, and the third individual is a
      young adult who left school after completing only 11 grades. Each student's word
      finding profile and characteristics are presented as well as the impact of the
      disorder upon school performance particularly in the area of reading.
      Recommendations are made for intervention involving collaboration between speech
      language pathologists and educators.

PMID- 7517272
TI  - Diphtheria in the United Kingdom: two recent imported cases.

PMID- 7517273
TI  - Salmonella infections, England and Wales: reports to the PHLS (salmonella data
      set).

PMID- 7517270
TI  - Characterization of four pupal wing cuticular protein genes of the silkmoth
      Antheraea polyphemus.
AB  - Three different clones have been isolated from a genomic library of the silkmoth
      Antheraea polyphemus by employing a subtractive hybridization technique. The
      clones with inserts of 13-16 kb of DNA each, code for mRNAs expressed in the wing
      epidermis during JH induced second pupal cuticle deposition. While two of the
      clones code for a single mRNA each, the third one codes for two mRNAs. All the
      four mRNAs code for distinct polypeptides that can be precipitated with
      antibodies raised against pupal cuticular proteins. These genes are activated at
      the same period of pupal development and their transcripts follow similar
      patterns of accumulation. Although these genes are expressed in a tissue and time
      specific manner attesting to their pupal wing epidermal specificity, three of
      them are expressed in the adult wing epidermis also, but not at the larval stage.
      While DNAs from other silkmoths and insects hybridize to these genes, only one of
      the A. polyphemus genes hybridizes to RNA from second pupal wings of two other
      silkmoths tested.

PMID- 7517274
TI  - Salmonella in humans, England and Wales: quarterly report.

PMID- 7517276
TI  - Using granulocyte colony-stimulating factor for neutropenia during neonatal
      sepsis.

PMID- 7517275
TI  - Experience with buccal phentolamine mesylate for impotence.
AB  - Satisfactory erection with penetration can be obtained in impotent men by the
      oral or buccal administration of the alpha-adrenergic antagonist, phentolamine.
      This agent is also used in conjunction with papaverine HCl for intracavernous
      injection. The previous observation by Gwinup, that 50 mg of phentolamine HCl po,
      1.5 hours before coitus resulted in erection in 11/16 patients, is confirmed.
      This study, using phenoxybenzamine as the placebo, was repeated with success in
      36/85 (42.3%) patients. Because of cost and to decrease the waiting time, a
      buccal form of phentolamine mesylate was administered (20 mg) with erection and
      penetration in 21/69 (31.8%). There was no correlation between the degree of
      penile vascular insufficiency or age and the effectiveness of phentolamine.
      Buccal phentolamine is shown to increase flow velocity in the dorsal penile
      artery. Phentolamine produces minimal side effects, including hypertension in the
      subjects.

PMID- 7517278
TI  - Experimental neurobiology of epilepsies.
AB  - Epileptic discharges are a pathological extreme of neuronal synchrony.
      Experimental models of both focal and primary generalized epilepsies reveal the
      importance of the interaction of intrinsic (membrane current) properties of
      neurons and the synaptic networks which connect them. Focal epilepsies depend on
      excitatory networks within individual cortical structures, but full seizures may
      require widely dispersed neuronal networks. Absence seizures are generated by the
      thalamocortical system, and depend on inhibitory postsynaptic potentials, Ca2(+)
      activated K+ currents and low threshold "T" currents. Other forms of
      synchronization can occur under particular circumstances, including field effects
      and gap junctions, but at the moment appear to be less generally involved in
      epileptogenesis. The cellular and network mechanisms of chronic experimental
      epilepsies are more complex and involve synaptic reorganization, and functional
      disconnection of inhibitory neurons.

PMID- 7517277
TI  - Developmental disorders.

PMID- 7517279
TI  - Altered calcitonin gene-related peptide, substance P and enkephalin
      immunoreactivities and receptor binding sites in the dorsal spinal cord of the
      polyarthritic rat.
AB  - The dorsal horn of the spinal cord, which forms the locus of first synapses in
      pain pathways, is an important site of interaction between calcitonin gene
      related peptide (CGRP), substance P and enkephalin--the neuropeptides considered
      to be especially involved in the regulation of pain perception. Since adjuvant
      induced arthritic rats provide a suitable model for peripheral inflammation and
      hyperalgesia, the possible alterations of immunoreactive CGRP, substance P and
      enkephalin as well as the binding sites for [125I]hCGRP alpha, [125I]substance
      P/neurokinin-1, (NK1) and [125I]FK-33-824/mu-opioid receptors were studied in the
      dorsal horn of the spinal cord receiving projections from the inflamed limbs. In
      arthritic rats compared to control animals, a bilateral increase in CGRP- and
      substance P-immunoreactive fibres and the presence of enkephalin-immunoreactive
      cell bodies were noted in the dorsal horn of the spinal cord. As for receptors,
      while a significant decrease in [125I]hCGRP alpha and [125I]substance P/NK1
      binding sites was observed in selective layers, no measurable alteration in
      [125I]FK-33-824/mu-opioid binding sites was noted in any regions of the arthritic
      rat dorsal horn compared to the unaffected control rats. Following unilateral
      section of the peripheral nerve prior to induction of arthritis, CGRP- and
      substance P-immunoreactive fibres were markedly depleted and no enkephalin
      positive neurons were observed in the ipsilateral dorsal horn. Analysis of
      receptor binding sites in denervated arthritic rats, however, exhibited
      differential responses, i.e. a significant increase in [125I]hCGRP alpha, a
      marked decrease in [125I]FK-33-824/mu-opioid and apparently no alteration in
      [125I]substance P/NK1 receptor binding sites were observed in the ipsilateral
      dorsal horn compared to the intact contralateral side. These results taken
      together provide anatomical evidence for a concerted role of these peptides in
      the regulation of adjuvant-induced hyperalgesia accompanying peripheral
      inflammation.

PMID- 7517281
TI  - Supernormal conduction in the left bundle branch.
AB  - This report describes a patient with tachycardia-dependent left bundle branch
      block (LBBB) and atrial extrasystoles, some of which were followed by an
      unexpectedly narrow QRS complex. His-bundle recordings and premature atrial
      stimulation were performed to analyze the mechanism underlying the normalized
      intraventricular conduction of some of the early atrial impulses. The results
      suggested the presence of supernormal conduction in the left bundle branch (LBB),
      because: (1) the HV interval was identical in LBBB complexes and in early narrow
      QRS complexes; (2) during single test stimulation using different paced atrial
      cycle lengths, there was a well-defined range of H1H2 intervals resulting in
      normalization of intraventricular conduction; and (3) atrial pacing with a cycle
      length of 500 msec resulted in alternation between wide and narrow QRS complexes.
      These findings rule out alternative mechanisms that could explain the
      unexpectedly normal intraventricular conduction of early impulses.

PMID- 7517280
TI  - Rostrocaudal subregional differences in the response of enkephalin, dynorphin and
      substance P synthesis in rat nucleus accumbens to dopamine depletion.
AB  - Quantitative in situ hybridization histochemistry was used to examine the effects
      of unilateral 6-hydroxydopamine lesions of the ascending dopaminergic fibres on
      levels of mRNA encoding the neuropeptides enkephalin, dynorphin and substance P
      in subregions of the nucleus accumbens. The nucleus accumbens was divided into
      quadrants and changes in mRNA were measured along the rostrocaudal extent of the
      nucleus. Two weeks after the lesion an increase was found in enkephalin mRNA in
      the lesioned side compared to the non-lesioned side, whereas a decrease was
      observed for dynorphin and substance P mRNA. The changes in mRNA levels differed
      from quadrant to quadrant and were not uniformly distributed along the
      rostrocaudal axis. Both types of changes, i.e. increase and decrease, were much
      higher in rostral parts of the nucleus than in caudal parts, indicating regional
      differences in the effects of blockade of the dopaminergic neurotransmission. The
      lesion-induced increases and decreases in mRNA levels occurred in both the shell
      and the core subregions of the nucleus accumbens and were not specifically
      related to either of these areas. Factors are discussed that may contribute to
      the rostrocaudal gradient in the changes of enkephalin, substance P and dynorphin
      mRNA levels. On the basis of their afferent and efferent connections, the rostral
      and caudal parts of the nucleus accumbens are considered to be involved in
      different functions. The present results suggest that dopamine depletion may
      affect these functions in a differential manner.

PMID- 7517282
TI  - Is the "funny" current funnier than we thought?

PMID- 7517284
TI  - Clear lens extraction and intraocular lens implantation in normally sighted
      hyperopic eyes.
AB  - BACKGROUND: Currently used corneal refractive procedures do not offer a perfect
      solution for high hyperopia. This article proposes clear lens extraction and
      intraocular lens (IOL) implantation for the correction of high hyperopia.
      METHODS: Extracapsular clear lens extraction and posterior chamber IOL
      implantation was performed in 10 normally sighted eyes of five patients with a
      hyperopic spherical equivalent refraction between +7.88 and +9.75 D. The follow
      up period was 18 months. RESULTS: Mean uncorrected visual acuity improved from
      count fingers to 20/25. All eyes saw 20/30 or better without correction.
      Postoperative correction ranged from -0.37 to +0.50 diopters (mean, 0.01). The
      mean endothelial cell loss percentage at 18 months was 11.2% +/- 1.87% (range, 8%
      to 13%). CONCLUSIONS: The excellent results of contemporary cataract surgery, the
      reduced morbidity, patient satisfaction, as well as accuracy and rapid stability
      of the refraction suggest that clear lens extraction and IOL implantation are
      useful refractive procedures for the correction of high hyperopia.

PMID- 7517283
TI  - Characterization of the inherent error in a spherically-biased corneal topography
      system in mapping a radially aspheric surface.
AB  - BACKGROUND: Accurate measurement of corneal topography is crucial for many
      clinical applications. Also, the human cornea is known to be an asphere.
      Therefore, the purpose of this study was to quantitatively evaluate the accuracy
      of the EyeSys Corneal Analysis System in measuring a radially aspheric test
      surface and characterize the error function. METHODS: Curvature of a calibrated
      ellipsoid was determined using three techniques: 1) calculating theoretically, 2)
      modeling with a spherically-biased algorithm, and 3) measuring experimentally
      using the EyeSys system, both with the surface aligned and under conditions of
      misalignment. RESULTS: The inherent error steadily increased from center to
      periphery, with a maximum error greater than 3.00 diopters at a radius of 4 mm
      for an eccentricity of 0.5 and apical radius of curvature of 7.5 mm. CONCLUSIONS:
      The EyeSys Corneal Analysis System does not accurately measure the instantaneous
      radii of curvature of an ellipsoid. Misalignment error is small compared to the
      inherent error due to a spherically-biased reconstruction.

PMID- 7517286
TI  - Visual function before and after photorefractive keratectomy for myopia.
AB  - BACKGROUND: To date, Snellen visual acuity and postoperative refraction have been
      used to evaluate the results of photorefractive keratectomy. However, other
      parameters, such as contrast sensitivity function and glare, may be affected by
      refractive surgery and lead to unsatisfactory visual performance. This
      prospective study is aimed at evaluating the effect of photorefractive
      keratectomy on contrast sensitivity function and glare. SUBJECTS AND METHODS:
      Static contrast sensitivity function, dynamic contrast sensitivity function, and
      glare sensitivity were evaluated in 22 myopic eyes before as well as 1, 3, and 6
      months after photorefractive keratectomy. The eyes tested were divided into three
      groups, according to the amount of myopia: group I, from -4.00 to -8.00 diopters
      (D); group II, from -8.25 to -11.00 D; group III, from -11.25 to -20.00 D.
      RESULTS: Both static and dynamic contrast sensitivity function at the
      intermediate spatial frequencies were altered at 1 month after photorefractive
      keratectomy, with a trend toward recovery at 3 and 6 months postoperatively.
      Glare sensitivity was not significantly affected by surgery. CONCLUSIONS:
      Contrast sensitivity function and glare testing may show abnormalities in the
      presence of optimal visual and refractive results. These tests may result
      especially important for the evaluation of new refractive surgical procedures.

PMID- 7517285
TI  - Corneal power correction factor for photorefractive keratectomy.
AB  - BACKGROUND: Studies of corneal power changes resulting from photorefractive
      keratectomy generally rely on keratometer or videokeratograph measurements. These
      instruments convert corneal radius of curvatures values to optical powers by
      means of the single refracting surface formula, which incorporates an index of
      refraction value of 1.3375. This index approximates that of the tears but not the
      1.376 index of the corneal epithelium or stroma. A hypothetical optical model was
      used to determine the most appropriate index to be chosen with respect to corneal
      power calculations relative to photorefractive keratectomy. METHODS: The
      contribution of each refractive element in the tear lens-corneal surface to the
      total power of the eye was calculated in order to identify which index of
      refraction was most appropriate for the corneal power calculation. RESULTS: The
      outer tear surface has significant optical power but the tear layer as a whole
      has nearly zero power due to the offsetting negative power of the posterior test
      surface. There is no significant difference in the effective power of light
      leaving the corneal anterior surface when considered with or without the tear
      layer. Photorefractive keratectomy changes the epithelium and anterior surface of
      the corneal stroma, but does not affect the posterior stroma or other ocular
      media. Hence the refractive index for the corneal epithelium or stroma of 1.376
      should be used in converting radius to optical power values. The error in
      assuming a corneal index of 1.3375 is a constant proportion equal to 11.4% of the
      corneal power reading. CONCLUSIONS: Photorefractive keratectomy presents a
      situation in which the actual corneal refractive index of 1.376 should be used
      for correct corneal radius to power conversions. This may be accomplished by
      changing the index value in the instrument algorithm for keratometry and
      videokeratography to 1.376 or by adding a correction factor of either 11.4% of
      the regular reading to its value or multiplying by the factor 1.114. In other
      applications of keratometry or videokeratography, the index 1.3375 may be more
      appropriate.

PMID- 7517287
TI  - Evaluation of corneal thickness and endothelial cells before and after excimer
      laser photorefractive keratectomy.
AB  - BACKGROUND: The possible endothelial damage induced by photorefractive
      keratectomy was investigated in myopic eyes. METHODS: A morphometric analysis of
      the endothelial cells was performed in 19 patients before and 2 months after
      photorefractive keratectomy for the correction of various degrees of myopia.
      Central ultrasonic pachometry was also recorded at the same examination times.
      RESULTS: No significant changes (p = .816) of the endothelial cell density were
      found between preoperative and postoperative measurements. The pleomorphic index
      did not show any significant changes after treatment (p = .955). Central corneal
      thickness was reduced to a various extent (range from 50 microns to 250 microns)
      according to the amount of myopic correction intended. CONCLUSIONS: Our
      preliminary data suggest that photorefractive keratectomy for the correction of
      myopia does not induce endothelial cell damage, at least in the short term.

PMID- 7517289
TI  - Aerosol application of cyanoacrylate adhesive.
AB  - BACKGROUND: Cyanoacrylate adhesive has been used to treat corneal perforations
      and stromal melting disorders. We examined the efficacy of aerosolization as a
      means of applying cyanoacrylate to the cornea. METHODS: Central corneal
      perforations were created with a 1-millimeter trephine in cadaver eyes. A small
      amount of N-butyl cyanoacrylate was delivered to the perforation site via
      aerosol. Experiments were also conducted with cadaver eyes which had received
      lamellar keratectomies to stimulate corneal thinning disorders. RESULTS: Adequate
      seal of the 1-millimeter perforation was achieved following aerosol application
      of cyanoacrylate adhesive. In experiments conducted with eyes which had been
      perforated and those which received lamellar keratectomies, smooth anterior
      surface contours were achieved using the aerosol technique. CONCLUSIONS:
      Aerosolization may be an effective method of applying cyanoacrylate adhesive.

PMID- 7517288
TI  - Electron microscopic evaluation of intrastromal corneal rings explanted from
      nonfunctional human eyes.
AB  - BACKGROUND: Intrastromal corneal rings (ICRs) often exhibit small deposits in
      association with their suture holes. We assessed the morphology of four such
      deposits. METHODS: Four ICRs, explanted from nonfunctional human eyes, were
      examined by scanning electron microscopy and transmission electron microscopy.
      RESULTS: The surface of the suture hole deposits consisted of a disorganized
      convolution of collagenous lamellae. Within individual lamellae, however, the
      collagen fibrils tended to orientate parallel with one another. The deposits
      consisted of an amorphous material interspersed with curved cellular processes,
      collagen fibrils of variable diameter, and proteoglycan macromolecules.
      CONCLUSIONS: We propose that the mechanism which regulates stromal remodeling is
      amended in the region of the ICR suture holes. Due to their location, suture hole
      deposits have no optical significance; however, evaluation of their morphology
      provides insights into the wound-healing properties of the corneal stroma
      following ICR insertion.

PMID- 7517290
TI  - Corneal stability and avoidance of hyperopia following incisional keratotomy.

PMID- 7517292
TI  - Excimer laser: a step-up in complexity and responsibility for the ophthalmic
      laser surgeon?

PMID- 7517293
TI  - Excimer laser photorefractive keratectomy for myopia: comparison of 4.00- and
      5.00-millimeter ablation zones.
AB  - BACKGROUND: To date, there has been no systematic study of the effects of
      ablation zone diameter on the outcome of photorefractive keratectomy. To address
      these issues, we examined a series of eyes with bilateral corrections using
      different-sized ablation zones. METHODS: Thirty-three patients underwent
      bilateral photorefractive keratectomy (Summit Excimed UV200, Waltham, Mass) with
      identical dioptric corrections in both eyes, except first eyes had 4.00
      millimeter and second eyes had 5.00-millimeter ablation zones. Identical
      postoperative eyedrop regimens were used in both eyes of each subject and the
      interval between treatments was 12 months. The mean depth of the programmed
      central ablation was 24 microns in eyes treated with 4.00-millimeter and 39
      microns with 5.00-millimeter zones. RESULTS: There was no statistically
      significant difference in the preoperative refraction between first and second
      eyes. Mean changes in refraction at 1, 3, 6, 9, and 12 months were significantly
      greater in eyes treated with 5.00-millimeter ablation diameters (p < .001). No
      eyes treated with 4.00-millimeter zones were overcorrected, but five eyes (15%)
      treated with 5.00-millimeter beams had a refraction greater than +1.00 diopter
      (D) at 12 months postoperatively. There was no significant difference in the
      amount of anterior stromal haze between the two eyes at any stage. In 14
      patients, less night halo was noticed in the eye treated with a 5.00-millimeter
      zone. Using a computer program, halo measurements were made in both eyes of 12
      patients whose pre- and postoperative refractions were within 0.50 D. The
      magnitude of halo was significantly less in eyes treated with 5.00-millimeter
      zones (p < .01). CONCLUSIONS: Despite greater depths of stromal ablation with
      5.00-millimeter diameters, there was no increased anterior stromal haze or
      postoperative regression of refraction. The biological and physical constraints
      governing the optimum size of the photorefractive keratectomy ablation zone are
      discussed.

PMID- 7517291
TI  - FDA panel recommends conditional approval of excimer laser phototherapeutic
      keratectomy (PTK)

PMID- 7517297
TI  - Retreatment of undercorrected photorefractive keratectomy for myopia.
AB  - Fourteen eyes treated by photorefractive keratectomy (PRK) for myopia required
      retreatment because of undercorrection. The mean preoperative refraction of these
      eyes had been -9.82 D (range 5.25 to 17.13). No eyes before photorefractive
      keratectomy had low myopia, three eyes had myopia between -3.10 and -6.00 D, four
      were between -6.10 and -10.00 D, and seven had more than -10.00 D of myopia.
      Retreatment was required for manifest scars in association with regression,
      unresponsive to topical corticosteroids. The retreatments were performed using a
      Summit ExciMed UV200LA excimer laser with a dual ablation technique utilizing a
      phototherapeutic keratectomy followed by a photorefractive keratectomy. Follow-up
      ranged from 1 to 9 months. Eight eyes followed more than 3 months had a mean
      spherical equivalent refraction of -0.58 D (range -7.35 to +1.25).

PMID- 7517295
TI  - Laser corneal surgery proceedings of the Third Annual Congress of the Summit
      International Laser User Group. Montreaux, Switzerland, September 17-19, 1993.

PMID- 7517296
TI  - Photorefractive keratectomy for myopia of more than -10 diopters.
AB  - Twenty-seven consecutive eyes of 18 patients with myopia of more than -10.00
      diopters (D) were treated by photorefractive keratectomy (PRK) using the ExciMed
      UV200LA excimer laser and a double ablation technique in an attempt to achieve a
      refraction of plano. The preoperative mean spherical equivalent refraction was 
      13.32 D (standard deviation 2.54, range -10.25 to -20.50). Preoperative spectacle
      corrected visual acuity ranged from 6/6 to 6/60 and one eye had had two previous
      refractive keratotomies. Follow up ranged from 3 to 15 months (mean 8.9). At 6
      months after surgery, the mean change in refraction was 11.03 D, from a
      preoperative mean of -13.32 D to a postoperative mean of -2.29 D. The mean
      keratometric flattening was 5.83 D, from a preoperative mean of 42.92 D to a
      postoperative mean of 39.09 D. The reason for this large difference is uncertain.
      At three months the mean spherical equivalent refraction was +0.07 D (SD 2.94,
      range -10.50 to +3.25). The 14 eyes that had achieved 12 months follow up had a
      mean spherical equivalent of -1.91 D (SD 3.87, range -11.00 to +2.50). Seven of
      these 14 eyes have been reablated for manifest scars in association with
      regression. All 14 eyes had best spectacle corrected visual acuity at or better
      than their preoperative level.

PMID- 7517298
TI  - Photorefractive keratectomy for myopia: one-year follow-up in 97 eyes.
AB  - We made a comprehensive study of 97 eyes that received photorefractive
      keratectomy (PRK) for myopia and followed them for one year. In 95 eyes,
      uncorrected visual acuity improved and best-corrected acuity remained unchanged.
      In eyes with myopia of more than -3.0 diopters (D), the postoperative refraction
      was within -1.0 D of attempted correction. Predictability decreased with higher
      myopia. We also examined the changes of both epithelium and endothelium with the
      specular microscope and found no significant changes after photorefractive
      keratectomy. Videokeratography showed an average of inferior decentration in most
      eyes by 0.51 mm +/- 0.31 (n = 60); only one clinical problem was noted--one eye
      experienced monocular diplopia for seven months. Pachometry showed a small
      percentage had corneal thinning--the amount depended on the degree of myopia. A
      rise in intraocular pressure over 21 mm Hg was observed in 8.9% of eyes but it
      was controlled without surgery. Haze was observed in most eyes, but faded
      gradually without significant problems. Reduced contrast sensitivity in night
      vision was noted and some patients experienced glare. Day vision contrast
      sensitivity was related to corneal haze.

PMID- 7517294
TI  - Cytotoxicity of viscoelastics on cultured corneal epithelial cells measured by
      plasminogen activator release.
AB  - BACKGROUND: Plasminogen activator has been shown to be released by epithelial
      cells following corneal injury. The demonstration of the release of plasminogen
      activator from cultured corneal epithelial cells has been used for developing a
      cytotoxicity test, the Corneal Epithelial Plasminogen Activator test, which
      compares changes in the level of plasminogen activator in tissue culture media
      following chemical exposure as an index of chemical injury. METHODS: Cultured
      rabbit corneal epithelial cells were exposed to varying concentrations of several
      viscoelastics for 1 hour. Release of plasminogen activator into the tissue
      culture media following exposure to the viscoelastic agent was studied as an
      index of chemical injury. RESULTS: The least cytotoxicity to cultured rabbit
      epithelium was associated with those viscoelastic agents containing
      methylcellulose. A 1-hour exposure to most concentrations of methylcellulose and
      chondroitin sulfate (Phacote) and methylcellulose (Occucoat) demonstrated release
      of greater amounts of plasminogen activator than was seen following a similar
      exposure to balanced salt solution, suggesting the greatest protective effect of
      these two viscoelastics. In contrast, sodium hyaluronate and chondroitin sulfate
      (Viscoat) showed decreased amounts of plasminogen activator release after a 1
      hour exposure to cultured corneal epithelial cells demonstrating cytotoxicity.
      Polyacrylamide (Orcolon) and most diluted preparations of sodium hyaluronate
      (Healon and Healon Yellow) showed only mild reductions in the release of
      plasminogen activator, whereas undiluted sodium hyaluronate preparations were
      nearly as cytotoxic as Viscoat. CONCLUSIONS: This study suggests that
      viscoelastic agents containing methylcellulose (Phacote and Occucoat) may be most
      protective of the corneal epithelium during ophthalmic surgery. The clinical
      success of several dilute viscoelastic solutions as tear substitutes was
      corroborated by the lack of cytotoxicity seen in this study. Viscoat and
      undiluted sodium hyaluronate preparations showed the greatest cytotoxicity to
      cultured rabbit corneal epithelium.

PMID- 7517300
TI  - Short-term corneal endothelial changes after photorefractive keratectomy.
AB  - Clinical results show that photorefractive keratectomy (PRK) offers good
      predictability, efficacy, and safety. However, its potential risks on the human
      corneal endothelium are poorly known. We report the results of a prospective
      study conducted to evaluate the corneal endothelium changes after photorefractive
      keratectomy. Preoperative and serial postoperative specular microscopy was
      performed in 14 eyes undergoing excimer laser photorefractive keratectomy. The
      endothelium was analyzed for a variety of parameters, including cell density,
      coefficient of variation in cell size, and hexagonality. The follow-up was 6
      months. The mean cell density was unchanged from 2463 cells/mm2 to 2498 cells/mm2
      at 6 months after photorefractive keratectomy. The coefficient of variation of
      cell size (polymegathism) changed from 0.303 to 0.280 at 1 month, to 0.293 at 3
      months, and to 0.290 at 6 months after surgery. The changes in this parameter
      were statistically significant when comparing pre- versus 1 month postoperative
      values. The hexagonality was unchanged from 72.08% at baseline to 73.35% at 6
      months. No endothelial abnormalities were found after photorefractive
      keratectomy. Our results suggest a cell migration from the peripheral to central
      cornea after photorefractive keratectomy in contact lens wearing patients prior
      to photorefractive keratectomy.

PMID- 7517299
TI  - The learning curve in myopic photorefractive keratectomy.
AB  - BACKGROUND: The aim of this study was to assess the role of surgeons' skill on
      the final results of photorefractive keratectomy (PRK) in the correction of
      myopia. METHODS: We evaluated the results of 160 consecutive unilateral
      treatments performed by four surgeons in a multicenter study group, with a one
      year follow up. Eighty-eight patients were males (55%) and 72 females (45%). Mean
      age was 33.7 years (median = 33, standard deviation = 10.22, range 18-65).
      Attempted correction ranged between -1.50 and -15.00 D. All the eyes received
      topical corticosteroid therapy postoperatively. At the one year follow up, we
      evaluated the following: uncorrected visual acuity lines gained and refractive
      error (spherical equivalent) as parameters of efficacy and predictability; best
      spectacle corrected visual acuity loss and corneal clarity as safety parameters.
      We also examined the centration or decentration of the ablation zone. In order to
      draw up a kind of learning curve, the mean values for each parameter were
      calculated by arbitrarily grouping the first 10 cases of each surgeon in the
      first group (40 patients), the second 10 cases in the second group (40 patients)
      and so on. RESULTS: We found that increase in uncorrected visual acuity, final
      refractive error and corneal clarity appeared to improve as the surgeon became
      more experienced, while loss of best spectacle corrected visual acuity was not
      significantly influenced by increased surgical experience. CONCLUSIONS: We think
      experience with photorefractive keratectomy in at least 40 eyes is necessary to
      obtain best results.

PMID- 7517303
TI  - Measurement of corneal thickness by ultrasound after photorefractive keratectomy
      in high myopia.
AB  - BACKGROUND: Photorefractive keratectomy (PRK) has been used to treat myopia in
      human eyes since 1988. METHODS: We evaluated corneal ablation depth after excimer
      laser myopic photorefractive keratectomy with the Summit Technology ExciMed
      UV200LA laser. Preoperative refraction was: mean 9.58 diopters (D) +/- 2.01,
      (range 6 to 17). We used ultrasound pachometry (1640 m/sec) in 40 eyes of 33
      patients. Mean follow-up was of 49.5 weeks (range 16 to 76). RESULTS: The
      measurement of the corneal thickness showed a reduction of the initial thickness
      followed by an inconsistent increase caused by wound healing and tissue
      proliferation. CONCLUSION: The data showed no direct correlation between diopters
      of refractive correction and the change in corneal thickness.

PMID- 7517301
TI  - Photorefractive keratectomy in 176 eyes: one year follow-up.
AB  - Beginning in March 1992, 176 eyes from 176 patients underwent photorefractive
      keratectomy with the Summit Technology Eximed UV200LA. This study was designed to
      evaluate the efficacy of this method.

PMID- 7517304
TI  - Transverse keratotomy combined with spherical photorefractive keratectomy for
      compound myopic astigmatism.
AB  - This is a report of a study of 40 eyes in which transverse keratotomy was
      performed in conjunction with spherical photorefractive keratectomy. The
      preoperative range of myopia was -1.50 to -13.50 diopters (D). The mean attempted
      cylindrical correction was -1.73 D (range -0.75 to -4.00). After 6 months 47.8%
      achieved unaided visual acuity of 6/6, 60% achieved 6/9 or better and 75%
      achieved 6/12 or better. The mean postoperative spherical equivalent refraction
      was -0.01 D at 6 months. The mean astigmatism postoperatively was 0.32 D. A group
      of 179 eyes with six months follow-up after photorefractive keratectomy who had
      not had transverse keratotomy was compared. Their mean postoperative spherical
      equivalent refraction was -0.07 D and mean astigmatism was 0.21 D. Uncorrected
      visual acuity was 6/12 or better in 93.3%. Until there is an improvement in the
      mechanism of the ablatable mask this combined procedure offers patients with
      significant astigmatism the opportunity of achieving good visual results.

PMID- 7517305
TI  - The treatment of pain following photorefractive keratectomy.
AB  - The most effective management of the pain that follows excimer laser
      photorefractive keratectomy (PRK) appears to be the use of topical nonsteroidal
      anti-inflammatory agents. A bandage contact lens for 2 days after photorefractive
      keratectomy is additive to pain relief. The helpfulness of patching was not
      confirmed. Surprisingly, drops of local anesthetic were not an efficacious means
      of managing the pain. This was possibly because they were not used frequently
      enough. The findings showed trends, but were not statistically significant.

PMID- 7517302
TI  - Photorefractive keratectomy following penetrating keratoplasty.
AB  - We present 3 eyes that underwent photorefractive keratectomy (PRK) for residual
      myopia after penetrating keratoplasty, and 1 eye that was treated for recurrent
      granular dystrophy and myopia following penetrating keratoplasty. The 3
      refractive eyes experienced improvements in visual acuity and refractive error
      through 3 months postoperative, but exhibited regression of effect after 6 months
      postoperative. One eye also exhibited substantial corneal haze at three months
      postoperative that was not responsive to steroid retreatment. The eye with
      granular dystrophy obtained symptomatic relief as well as improvement in vision.
      We tentatively conclude that the corneal transplant reacts to photorefractive
      keratectomy in much the same way as a normal cornea. Eyes with substantial
      degrees of post-graft myopia exhibit regression of refractive effect, much like
      high myopes following primary photorefractive keratectomy. Photorefractive was
      unable to prevent the recurrence of granular dystrophy in the transplanted
      tissue. The eyes reported here achieved only modest long-term visual and
      refractive improvements.

PMID- 7517306
TI  - Some problems after photorefractive keratectomy.
AB  - We analyzed the data from 1821 patients (2920 eyes) who received photorefractive
      keratectomy (PRK) to investigate the postoperative complications which cause a
      significant decrease in visual acuity. A corneal haze of grade 2 or more
      developed in 9 patients (11 eyes, 0.38%) and corticosteroid-induced ocular
      hypertension occurred in 3 patients (4 eyes, 0.14%). Three patients (4 eyes) who
      had corneal haze of grade 2 or more underwent repeated photorefractive
      keratectomy and one patient (2 eyes) with steroid-induced ocular hypertension
      underwent trabeculectomies. A decrease of best spectacle corrected visual acuity
      of two lines or more was detected in 7 patients (8 eyes, 0.27%), caused by
      irregular astigmatism, steroid-induced cataract, incidental choroidal neovascular
      membrane, and an unknown origin. Good predictability and stabilization after
      photorefractive keratectomy was maintained at the 2 year follow-up. However, some
      subjective symptoms were reported by many patients and some complications
      occurred in a minority of eyes despite the excellent visual outcome in a large
      majority.

PMID- 7517308
TI  - Photorefractive keratectomy for residual myopia after previous refractive
      keratotomy.
AB  - Photorefractive keratectomy (PRK) was performed on 91 eyes of 71 patients who had
      previous radial keratotomy, radial combined with astigmatic keratotomy or
      astigmatic keratotomy alone (refractive keratotomy). Residual myopia, prior to
      photorefractive keratectomy, ranged from -1.50 to -8.00 D (mean -3.62) and
      cylinder from 0 to 2.25 D (mean 0.78). Uncorrected visual acuity was 20/40 or
      better in 89.7% at one year. At the 12 month follow-up 75.9% of patients were
      within +/- 1.00 D of intended correction.

PMID- 7517307
TI  - Photorefractive keratectomy for myopia in 98 eyes.
AB  - Photorefractive keratectomy (PRK) was performed on 98 consecutive normal myopic
      eyes with the Summit OmniMed laser System. The minimum follow-up was 3 months and
      31 were followed for 6 months. Preoperative myopia ranged from -1.25 to -12.00 D.
      The myopic eyes were divided into 4 groups according to the amount of myopia:
      group 1 (-1.25 to -3.00 D), 17 eyes; group 2 (-3.12 to -6.00 D), 42 eyes; group 3
      (-6.12 to -9.00 D), 29 eyes and group 4 (> 9.00 D), 10 eyes. In group 1 mean
      uncorrected visual acuity was 0.87 at 3 months, 1.0 at 6 months and all of the
      eyes were within 0.50 D of the attempted correction. In group 2 mean uncorrected
      visual acuity was 0.76 at 3 months, 0.87 at 6 months and 92.3% of the eyes were
      within 0.50 D of the attempted correction. In group 3 mean uncorrected visual
      acuity was 0.65 and 0.66 at 3 and 6 months respectively and 77.8% of eyes were
      within 0.50 D of the attempted refractive correction. In group 4, mean
      uncorrected visual acuity was 0.46 and 0.7 at 3 and 6 months, respectively, and
      100% were within 0.50 D of the attempted correction. Two eyes lost 2 lines and 4
      eyes gained 2 or more lines of their preoperative best spectacle corrected visual
      acuity. Three eyes exhibited steroid induced rise in intraocular pressure that
      was controlled with topical timolol. No serious complications occurred. Despite
      the short follow-up, photorefractive keratectomy with the 193 nm excimer laser
      appears to be an effective and safe treatment for the correction of myopia.

PMID- 7517309
TI  - Treatment of myopic astigmatism with photorefractive keratectomy using an
      erodible mask.
AB  - The Summit Technology erodible mask treatment of astigmatism does not alter the
      keratometric astigmatism significantly, even though the refractive astigmatism
      appears to improve by about 50%. Myopia is satisfactorily treated with the
      erodible mask, but there is slightly more undercorrection compared to
      photorefractive keratectomy (PRK) using an expanding diaphragm. Increasing the
      minus power in ordering the mask cylinder improves the myopia result, but not the
      keratometric astigmatism result. The following factors do not influence the
      keratometric astigmatism result: 1) The type of astigmatism (with-, against-the
      rule, or oblique); 2) The initial keratometry readings; and 3) The time from the
      commencement of epithelial removal to laser treatment.

PMID- 7517312
TI  - Keratomileusis-in-situ using manual dissection of corneal flap for high myopia.
AB  - Overcorrection, regression and haze are some side-effects found after excimer
      laser photorefractive keratectomy (PRK) for high myopia. A new method attempts to
      avoid photoablation through Bowman's layer, using the stroma to flatten the
      cornea without use of a microkeratome. Manual surgical instruments such as the
      diamond blade, spatula, Pierce forceps, and Vannas scissors are used to remove a
      disc of anterior cornea. Minimal topical corticosteroids are used, avoiding the
      complications of prolonged corticotherapy. Six eyes underwent manual excimer
      laser keratomileusis-in-situ. Postoperatively, the epitheliums in these eyes
      initially were dry and excoriated. By the twentieth day, however, the eyes had re
      epithelialized and recovered. The optical effect is the same as when
      keratomileusis is used. No more than three-fourths of the pre-existing myopia was
      used in the program as some undercorrection was desired.

PMID- 7517313
TI  - Energy fluctuations in an excimer laser during photorefractive keratectomy.
AB  - We performed an experiment with the MEL 60 excimer laser (Aesculap Meditec
      Technology) to demonstrate the variations of energy of the laser beam that could
      happen during a refractive surgical procedure. In order to quantify such
      variations, we measured the whitening of a photographic paper after a series of
      exposures to the laser beam with the X rite 400 B/W reflection densitometer. The
      energy fluctuations noted between two series of pulses averaged 11.02% (minimum
      0; maximum 46). These fluctuations tended to decrease progressively during the
      procedure. The energy of the laser beam decreased with time. At the end of the
      experiment, the total loss of energy was 45.16%. These results suggest that
      clinically meaningful energy variations could happen during the photorefractive
      keratectomy and reduce refractive predictability.

PMID- 7517315
TI  - OmniMed II: a new system for use with the emphasis erodible mask.
AB  - Clinical experience has shown the emphasis erodible mask to be an effective
      method for performing photorefractive keratectomy (PRK) using an eyecup placed in
      contact with the corneal surface. A new system (OmniMed II) which incorporates
      the erodible mask as an element in the optical delivery system has been developed
      for performing photorefractive keratectomy. With this new configuration the
      eyecup is no longer used. We describe in detail the advantages of the erodible
      mask, the associated hardware of the optical delivery system, and the mask shape
      transfer process.

PMID- 7517314
TI  - Cooling the cornea to prevent side effects of photorefractive keratectomy.
AB  - Complaints after photorefractive keratectomy (PRK) include both severe pain and a
      decrease in quality of vision due to corneal subepithelial haze. We suspect that
      one of the causes of these troubles is a temperature rise at the corneal surface
      during ablation. We cooled down the eye with cold balanced salt solution before
      and after photorefractive keratectomy. Postoperatively, this reduced severe pain,
      subepithelial corneal haze and any damage to the corneal endothelium.

PMID- 7517310
TI  - A simplified method to perform photorefractive keratectomy using an erodible
      mask.
AB  - BACKGROUND: Photorefractive keratectomy (PRK) using the current erodible mask
      technique is difficult to perform, because of the stringent requirements in the
      alignment of the eye to the mask and in the centration of the mask under the
      laser beam. The surgeon has to manually control the eye-cup over 5 degrees of
      freedom. If not accurately done this may lead to decentration of the ablation and
      bring about technical problems during treatment. The aim of this study was to
      find a way to improve and simplify the erodible mask procedure. METHOD: We used a
      modified non-contact mask eye-cup with a rigid mechanical support to obtain a
      precise and reliable positioning in space of the mask itself. Eye centration over
      the pupillary aperture was obtained with conventional patient fixation on the
      reference aiming light, coaxial to the laser beam path, and controlled using two
      He-Ne beams aimed at the corneal apex. RESULTS: Good reliability was demonstrated
      in the first 22 eyes operated on using this technique. All the masks were ablated
      with good centration of the laser beam over the polymethylmethacrylate (PMMA)
      button, and all the treatments were satisfactorily centered over the pupillary
      aperture. No complications or side effects were encountered during the
      treatments. CONCLUSIONS: Compared to the conventional erodible mask procedure,
      this technique proved much faster to perform, was more comfortable for both
      patient and surgeon, and was technically easier for the operator.

PMID- 7517311
TI  - Correction of myopia and astigmatism using an ablatable mask.
AB  - BACKGROUND: Most excimer laser refractive procedures use a computer driven
      mechanical diaphragm to shape the laser beam. Studies are currently underway
      using an ablatable polymethylmethacrylate (PMMA) mask to transfer a new spherical
      or toric curve to the cornea for the correction of myopia and astigmatism; it may
      leave a smoother corneal surface than diaphragm procedures. METHODS: As part of a
      Phase IIb FDA clinical study, 25 eyes of 25 patients underwent excimer laser
      photorefractive keratectomy using a hand held ablatable mask. Fifteen eyes had
      attempted spherical corrections of up to 6.00 diopters (D) and 10 had toric
      corrections of up to 6.00 D of sphere and 2.75 D of astigmatism. RESULTS: Seventy
      four percent of all eyes achieved uncorrected visual acuity of 20/40 or better-
      86% in the spherical group and 63% in the astigmatism group. Sixty-nine percent
      of eyes were within +/- 1 D of the attempted correction. In eyes treated for
      astigmatism, mean astigmatism decreased from 1.48 D preoperatively to 0.86 D
      postoperatively. Approximately one half of the eyes treated for astigmatism had a
      decrease in cylinder of more than 0.5 D. One eye lost 2 Snellen lines of best
      spherical corrected visual acuity. Video keratography showed toric ablations to
      result in an elliptical optical zone. Analysis of centration of the procedure
      showed 66% of ablations centered within 1.0 mm of the center of the pupil
      aperture. CONCLUSIONS: The ablatable mask represents a promising modality for the
      treatment of eyes with both myopia and myopic astigmatism.

PMID- 7517316
TI  - Scraping of epithelium for treatment of undercorrection and haze after
      photorefractive keratectomy.
AB  - We report an easy, safe technique to treat regression and haze after excimer
      laser photorefractive keratectomy (PRK), in which the hyperplastic epithelium is
      removed manually. The results of scraping of epithelium in 21 eyes of 20 patients
      are presented. Mean follow-up time was 3 months (range 1 to 7). The mean
      spherical equivalent refraction before photorefractive keratectomy was -9.93 +/-
      2.95 diopters (D); the mean spherical equivalent refraction before epithelial
      scraping was -3.82 +/- 2.87 D; after scraping it declined to -2.63 +/- 4.04 D.
      The uncorrected visual acuity after scraping was 20/50 or better in 6 eyes. In 5
      others it was between 20/60 and 20/100, and in 10 eyes it was worse than 20/100.
      The corrected visual acuity after scraping was 20/30 or better in 8 eyes, between
      20/40 and 20/60 in 8 eyes, and between 20/60 and 20/100 in 5 eyes.

PMID- 7517318
TI  - Discrimination between the origins and functional implications of haze and halo
      at night after photorefractive keratectomy.
AB  - A series of 84 eyes with up to -6.00 diopters (D) of myopia were treated by
      photorefractive keratectomy (PRK) using a 5.00 mm ablation zone. Three months
      postoperatively, 43 eyes (51%) complained of disturbed night vision, compared to
      12 (14%) preoperatively. Ten (12%) had significant problems, ie, interference
      with driving at night. At 12 months, there were 32 patients (38%) with minor
      disturbances of night vision, 4 (5%) with significant problems.

PMID- 7517319
TI  - Astigmatic keratotomy followed by photorefractive keratectomy in the treatment of
      compound myopic astigmatism.
AB  - Eleven eyes of 9 patients that had compound myopic astigmatism were treated by
      astigmatic keratotomy followed 1 month later by photorefractive keratectomy
      (PRK). In 9 eyes arcuate incisions were performed, in 1 eye a modified Ruiz
      procedure was performed, and in 1 eye radial T cuts were done. The mean spherical
      equivalent was -8.26 +/- 2.51 diopters (D) after the astigmatic keratotomy but
      before photorefractive keratectomy, and -0.36 +/- 0.93 D after photorefractive
      keratectomy. The mean cylinder was -3.11 +/- 1.16 D preoperatively, and -0.14 +/-
      0.9 D postoperatively. Combined astigmatic keratotomy and photorefractive
      keratectomy are effective treatments for compound myopic astigmatism.

PMID- 7517320
TI  - Photorefractive keratectomy for the treatment of myopia after epikeratoplasty: a
      case report.
AB  - An aphakic eye with a +9.00 diopter (D) refraction developed high myopia of 
      13.00 D after applying epikeratoplasty using a +14.00 D lenticule. We preformed
      photorefractive keratectomy by excimer laser. The procedure was uneventful, with
      no postoperative pain. Epithelialization occurred as usual. Recovery of the
      cornea followed the usual course with initial overcorrection followed by certain
      regression. After 7 months follow-up the spherical equivalent was -3.25 D and the
      lenticule was clear. In myopia after epikeratoplasty photorefractive keratectomy
      is an effective alternative to lenticule exchange.

PMID- 7517321
TI  - Use of topical nonsteroidal anti-inflammatory drugs after photorefractive
      keratectomy.
AB  - BACKGROUND: Photorefractive keratectomy (PRK) requires a careful pharmacologic
      regimen during the postoperative period to reduce corneal haze and refractive
      myopic regression. Noncorticosteroidal anti-inflammatory drugs limit postablative
      corneal inflammation without the complications that may occur during
      corticosteroid treatment. METHODS: Twenty consecutive eyes of 10 patients with
      attempted correction ranging from 4.00 to 9.00 D of myopia were studied. During
      the postoperative period, corticosteroid drops (dexamethasone 0.1%) were
      instilled in the first eye of each patient, and the second eye was treated with
      diclofenac sodium ophthalmic solution 0.1% (Voltaren). Follow-up was 12 months
      after surgery. RESULTS: Corneal haze and refraction were studied. Six of the 10
      eyes treated with noncorticosteroidal anti-inflammatory drugs did not show any
      significant difference in corneal haze and refractive evolution compared to the
      contralateral eyes treated with corticosteroids. Two eyes (20%) showed less
      corneal haze and more refractive stability than the contralateral eyes. In two
      eyes (20%), we observed similar corneal haze but more refractive regression than
      in the contralateral eyes. CONCLUSIONS: Eyes treated with topical diclofenac
      sodium had a similar postoperative course as those treated with corticosteroids,
      but without the adverse effects of corticosteroids. Topical nonsteroidal anti
      inflammatory drugs are represented by diclofenac (Voltaren), which has
      significant ocular penetration. This permits reduction of the possibility of
      general and ocular complications that frequently occur with corticosteroids. The
      aim of this study was to evaluate the efficacy of topical nonsteroidal
      antiinflammatory drugs vs. corticosteroidal eyedrops after photorefractive
      keratectomy (PRK) to reduce moderate and high myopia.

PMID- 7517323
TI  - Laser corneal surgery. Bibliography.

PMID- 7517322
TI  - Phototherapeutic keratectomy in the treatment of corneal scarring from trachoma.
AB  - Trachoma is still one of the world's major blinding diseases. Characteristically,
      trachoma causes deep scarring of the conjunctiva and tarsus that can result in
      tear deficiency, trichiasis, and entropion. Another common finding is a diffused
      corneal opacity that is the end stage of peripheral and central corneal
      infiltrates. The conventional treatment of the corneal opacities is keratoplasty,
      which has a guarded prognosis because of severe dryness and trichiasis. We report
      on our experience in treating patients with corneal trachoma with
      phototherapeutic keratectomy (PTK) with the excimer laser.

PMID- 7517324
TI  - [Neoplasms in the elderly].

PMID- 7517317
TI  - Holmium:YAG laser thermokeratoplasty for hyperopia.
AB  - Holmium:YAG laser thermokeratoplasty (LTK), a procedure using a solid-state
      infrared laser to treat hyperopia, was performed on 10 patients in phase I and 16
      patients in phase II--in a total of 29 eyes at the Hunkeler Eye Clinic. Phase II
      was redesigned after phase I results showed undercorrection and regression. The
      follow-up period ranged from 1 to 24 months (mean 10.9 months). A total of 79% of
      phase II patients were within +/- 1.00 D of intended correction at the 6-month
      visit. Looking at both phases together, no patients had J2 or better near vision
      preoperatively, but 75% had J2 or better at the 6-month visit. A total of 43% of
      eyes in phase II lost 1 line and 7% lost two lines of best spectacle corrected
      visual acuity due to induction of irregular astigmatism. The surgical challenges
      are to insure appropriate centration of the procedure about the optical axis.
      Concerns about regression and stability will be defined as these patients are
      followed through their 2-year visits.

PMID- 7517327
TI  - Tachykinin NK1 receptor subtypes in the rat urinary bladder.
AB  - 1. Following the recent proposal that the selective agonist septide,
      ([pGlu6,Pro9]SP(6-11)), acts on a novel tachykinin receptor distinct from the
      'classical' NK1 receptor, the aim of the study was to investigate the possible
      heterogeneity of tachykinin NK1 receptors in the rat urinary bladder. 2. The
      synthetic tachykinin receptor agonists, septide (pD2 7.87) and [Sar9]substance P
      (SP) sulphone (pD2 7.64) produced concentration-dependent contractions of the rat
      isolated urinary bladder. 3. The NK1 receptor antagonists GR82,334, (+/-)
      CP96,345, and RP67,580 competitively antagonized (slopes of Schild plot not
      significantly different from unity) the response to septide with the rank order
      of potency (pKB values in parentheses): RP 67,580 (7.57) > GR 82,334 (7.01) > (+/
      )-CP 96,345 (6.80). The same antagonists were significantly less potent when
      tested against [Sar9]SP sulphone, while maintaining the same rank order of
      potency: RP 67,580 (7.00) > GR 82,334 (5.93) > (+/-)-CP 96,345 (< 6). The
      antagonists did not affect the concentration-response curve to bombesin. 4. To
      exclude the involvement of the NK2 receptor, a second series of experiments was
      performed in the presence of the potent nonpeptide NK2 receptor antagonist, SR
      48,968. SR 48,968 (1 microM) produced a rightward shift of the concentration
      response curve to the NK2 receptor selective agonist, [beta Ala8]neurokinin A
      (NKA) (4-10). SR 48,968 did not significantly modify the response to SP, NKA,
      neurokinin B (NKB), neuropeptide K (NPK), neuropeptide gamma (NP gamma), SP(4
      11), SP(6-11), septide or [Sar9]SP sulphone. 5. In the absence or presence of SR
      48,968, RP 67,580 antagonized in a competitive manner the response to septide,
      [Sar9]SP sulphone, SP(4-11) and SP(6-11): pKB values obtained in the absence and
      presence of SR 48,968 were not significantly different for any of these four
      agonists.6. RP 67,580 antagonized the response to SP and NKA both in the absence
      and presence of SR 48,968.In both cases, the slopes of the Schild plots were
      significantly different from unity. Mean dose-ratios produced by RP 67,580 in the
      presence of SR 48,968 were larger than those measured without NK2receptor
      blockade for both SP and NKA.7. RP 67,580 (3 MicroM) did not antagonize the
      response to NKB in the absence of SR 48,968. In the presence of SR 48,968, RP
      67,580 acted as a competitive antagonist of NKB-induced contractions with apKB
      value (7.63) not significantly different from that measured towards septide. In
      the present of SR48,968, RP 67,580, GR 82,334 and (+/-)-CP 96,345 antagonized the
      response to NKB with a rank order of potency identical to that measured towards
      septide or [Sar9]SP sulphone.8. In the absence of SR 48,968, RP 67,580 (3 MicroM)
      produced a small shift of the concentration-response curve to neuropeptide K and
      was ineffective toward neuropeptide T. In the presence of SR 48,968 a clear shift
      of the curve to both agonists was observed.9. These findings are compatible with
      the idea that a septide-sensitive tachykinin receptor may exist in the rat
      urinary bladder. The septide-sensitive receptor is recognized by NK1 receptor
      antagonists with higher affinity than the 'classical' NK1 receptor recognized by
      [Sar9]SP sulphone. Our data suggest that NKB, after NK2 receptor blockade, is a
      more suitable ligand than SP for activation of the 'septidesensitive'receptor.
      While the final proof for the existence of possible NK1 receptor subtypes must
      await confirmation at the molecular level, the present findings provide strong
      pharmacological evidence that either NK, receptor subtypes or a novel type of
      tachykinin receptor exist in the rat urinary bladder.

PMID- 7517326
TI  - Local anaesthetic blockade of neuronal nicotinic ACh receptor-channels in rat
      parasympathetic ganglion cells.
AB  - 1 The effects of the local anaesthetics QX-222 and procaine on nicotinic
      acetylcholine (ACh)-evoked currents in cultured parasympathetic cardiac neurones
      of the rat were investigated by use of the whole-cell, perforated-patch, and
      outside-out recording configurations of the patch clamp method. 2 QX-222 and
      procaine, applied to the extracellular surface, reversibly inhibited the peak
      amplitude of the whole-cell nicotinic ACh-evoked current in a concentration
      dependent manner, with half-maximal inhibitory concentrations (IC50) of 28 microM
      and 2.8 microM, respectively, at -80 mV. In these neurones, the sustained inward
      current mediated by M1 muscarinic receptor activation was unaltered by QX-222,
      and neither local anaesthetic affected the adenosine 5'-triphosphate (ATP)-evoked
      current. 3 QX-222 and procaine block of nicotinic ACh-evoked inward current was
      voltage-dependent and enhanced by hyperpolarization. An e-fold change in their
      dissociation equilibrium constants (Kd) resulted from a 62 mV and a 122 mV change
      in membrane potential, respectively. 4 Both local anaesthetics produce a
      concentration-dependent increase in the half-time of decay of the nicotinic ACh
      evoked inward current. 5 Measurements of unitary currents in outside-out patches
      showed that QX-222 reversibly increased the mean burst duration and closed time
      and reduced the mean channel open time and open-state probability of the
      nicotinic ACh receptor-channel (AChR) in a concentration-dependent manner. 6 The
      Kd and voltage sensitivity of local anaesthetic block of the nicotinic AChR in
      rat intracardiac neurones suggests that the pore-forming region of this channel
      differs from that of the AChR in frog and rat skeletal muscle and from the
      neuronal alpha 4 beta 2 ACh receptor-channel.

PMID- 7517325
TI  - Relaxation of rat thoracic aorta induced by the Ca(2+)-ATPase inhibitor,
      cyclopiazonic acid, possibly through nitric oxide formation.
AB  - 1 The effect of the Ca(2+)-ATPase inhibitor, cyclopiazonic acid (CPA), was
      studied on rat thoracic aortic ring preparations. 2 At concentrations above 0.3
      microM, CPA induced relaxation in the arteries precontracted with phenylephrine.
      Removal of the endothelium abolished CPA-induced relaxation. 3 The nitric oxide
      (NO) synthase inhibitor NG-nitro L-arginine (3-300 microM), the free radical
      scavenger haemoglobin (0.1-3 microM), the soluble guanylate cyclase inhibitor,
      LY83583 (0.1-10 microM), each inhibited the endothelium-dependent relaxation to
      CPA. The potassium channel blocker, glibenclamide (10 microM) and cyclo-oxygenase
      inhibitor, indomethacin (100 microM for 60 min and then washed out) did not alter
      the action of CPA. 4 The calmodulin inhibitors calmidazolium (3-10 microM) and W
      7 (100 microM) also abolished CPA-induced relaxation. 5 CPA (10 microM) increased
      guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in arteries with an
      intact endothelium, without affecting adenosine 3':5'-cyclic monophosphate
      (cyclic AMP) levels. 6 The inhibitors of NO synthesis and actions, the calmodulin
      inhibitor and removal of the endothelium abolished the CPA-stimulated increase in
      the levels of cyclic GMP. 7 In Ca(2+)-free solution, CPA failed to induce
      relaxation or to stimulate cyclic GMP production. Relaxation to nitroprusside was
      not affected under these conditions. 8 These results suggest that CPA can
      stimulate NO synthesis, possibly by inhibiting a Ca(2+)-ATPase, which replenishes
      Ca2+ in the intracellular storage sites in endothelial cells. Depletion of the
      Ca2+ store in the endothelium may then trigger influx of extracellular Ca2+,
      contributing to an increase in free Ca2+ in the endothelial cells, which
      activates NO synthase and NO formation.

PMID- 7517328
TI  - Characterization of NK1 and NK2 tachykinin receptors in guinea-pig and rat
      bronchopulmonary and vascular systems.
AB  - 1. NK1 and NK2 tachykinin receptors were characterized in guinea-pig and rat
      bronchopulmonary systems and in the vasculature of the rat by use of radioligand
      binding and/or functional studies. 2. The radioligands for NK1 and NK2 receptors
      ([3H]-SP and [3H]-pNKA, respectively) did not label tachykinin receptors in
      homogenates of rat lungs or bronchi. In contrast, in the guinea-pig, [3H]-SP
      bound with high affinity to these tissues (KD = 0.23 +/- 0.08 nM and 0.34 +/-
      0.05 nM, for lungs and bronchi, respectively). The total number of binding sites
      was 4.6 fold greater in bronchus (Bmax = 135 +/- 27 fmol mg-1 protein) than in
      lung homogenates (Bmax = 29.3 +/- 0.1 fmol mg-1 protein). Furthermore, this
      binding was markedly displaced by CP-96,345 (pKi = 9.5 +/- 0.1) and RP 67580 (pKi
      = 7.6 +/- 0.1), antagonists of NK1 receptors, slightly displaced by SR 48968 (pKi
      = 6.6 +/- 0.1), but not affected by actinomycin D or L-659,877, antagonists of
      NK2 receptors. Specific binding of [3H]-pNKA, detected in guinea-pig bronchi (KD
      = 5.2 +/- 0.1 nM, and Bmax = 203 +/- 19 fmol mg-1 protein) but not in lungs, was
      similarly (40 to 53%) displaced by RP 67580 (1 microM), CP-96,345 (10 and 100 nM)
      or SR 48968 (10 and 100 nM). The displacement approximately doubled (87 to 91%)
      when SR 48968 (10 nM) was combined with either RP 67580 (1 microM) or CP-96,345
      (10 nM), but not when RP 67580 was combined with CP-96,345. 3. In urethane
      anaesthetized guinea-pigs, i.v. injections of the NK1 receptor agonists SP,
      [Pro9]-SP, [Sar9,Met(O2)11]-SP and septide, as well as the NK2 receptor agonists
      NKA and [Lys5,MeLeu9,NLeu10]-NKA(4-10) (0.1-10 micrograms kg-1, i.v.), dose
      dependently increased lung inflation pressure. The most potent of these peptides
      were septide and [Lys5, MeLeu9,NLeu10]-NKA(4-10) (EC50 = 0.38 +/- 0.07 and 0.07
      +/- 0.02 microgram kg-1, respectively). Interestingly, septide was 130 fold less
      potent than SP in displacing [3H]-SP from its binding sites in the guinea-pig
      lung, whereas it was 14 fold more potent than SP as a bronchoconstrictor. RP
      67580 (0.3-5 mg kg-1, i.v.) and CP-96,345 (0.01-3 mg kg-1, i.v.) dose-dependently
      reduced the bronchoconstriction produced by the NK1 receptor agonists.
      Conversely, the NK2 receptor antagonists actinomycin D (1-10 mg kg-1, i.v.) and
      SR 48968 (0.03-0.3 mg kg-1, i.v.) inhibited specifically the responses induced by
      NK2 receptor agonists.4. In pentobarbitone-anaesthetized rats, the NK1 and NK2
      receptor agonists (0.01-4 microg kg-1, i.v.)produced dose-dependent hypotensive
      responses. The order of potency was SP = [Sar9, Met(0211]-SP = [Pro9]-SP >
      septide = NKA >[Lys5, MeLeu9, NLeu 10-NKA.(4-10). RP 67580 (0.13-0.5 mg kg
      1,i.v.) and CP-96,345 (0.5-2 mg kg-1, i.v.) antagonized in a dose-related manner
      (20 to 64%) the vascular effects of both NK, and NK2 receptor agonists, whereas
      actinomycin D (3 mg kg-1, i.v.) and SR 48968(2 mg kg-1, i.v.) did not. RP 67580
      was approximately 4 times more potent than CP-96,345.5. These studies indicate
      that NK1 and NK2 receptors are both present in the guinea-pig bronchopulmonary
      system whereas only NK1 receptors are detectable in the rat vasculature under our
      experimental conditions. Furthermore, NK1 receptors in the guinea-pig
      bronchopulmonary system are pharmacologically distinct from those present in the
      rat vascular system, since both agonist potencies and antagonist affinities
      differ between the two species.

PMID- 7517331
TI  - The 33 kDa protein of the oxygen-evolving complex: a multi-gene family in tomato.
AB  - A cDNA was isolated by chance from tomato which had a high similarity to a cDNA
      clone from potato known to code for the 33 kDa protein of the oxygen-evolving
      complex [van Spanje et al. (1991) Plant Mol. Biol. 17: 157]. The sequence of a
      previously described partial cDNA clone from tomato [Ko et al. (1990) Plant Mol.
      Biol. 14: 217] which has also a high similarity but is not identical to the
      sequence described here indicates that tomato contains at least two genes coding
      for 33 kDa proteins per haploid genome. This conclusion is supported by Southern
      blot analysis. The tissue specific expression of the corresponding genes is
      described.

PMID- 7517332
TI  - Intrathecal co-administration of morphine and excitatory amino acid agonists
      produce differential effects on the tail-flick of intact and spinal rats.
AB  - Previous reports, that intrathecal morphine is more potent on the tail-flick test
      of acute spinal rats than intact rats, suggested that spinal opiate analgesia was
      attenuated by neurotransmitter release from descending pathways. To determine if
      this phenomenon involved excitatory amino acids (EAAs), 0.25 nm of N-methyl-D
      aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid
      (AMPA) were i.t. co-administered with morphine to Intact and Spinal rats. NMDA
      potentiated morphine antinociception in Intact but not Spinal rats; AMPA had no
      effect in Intact rats, but significantly reduced morphine antinociception in
      Spinal rats. The data suggest a reciprocal descending, modulatory influence on
      the spinal interaction between EAAs and morphine.

PMID- 7517334
TI  - An RNA pattern matching program with enhanced performance and portability.

PMID- 7517330
TI  - Evidence that nitric oxide is an endogenous antiangiogenic mediator.
AB  - 1. The involvement of nitric oxide (NO) in the regulation of angiogenesis was
      examined in the in vivo system of the chorioallantoic membrane (CAM) of the chick
      embryo and in the matrigel tube formation assay. 2. Sodium nitroprusside (SNP)
      (0.37-28 nmol/disc), which releases NO spontaneously, caused a dose-dependent
      inhibition of angiogenesis in the CAM in vivo and reversed completely the
      angiogenic effects of alpha-thrombin (6.7 nmol/disc) and the protein kinase C
      (PKC) activator 4-beta-phorbol-12-myristate-13-acetate (PMA) (0.97 nmol/disc). In
      addition, SNP (28 x 10(-6) M) stimulated the release of guanosine 3'-5'-cyclic
      monophosphate (cyclic GMP) from the CAM in vitro. 3. In the matrigel tube
      formation assay, an in vitro assay of angiogenesis, both SNP (1-3 x 10(-6) M) and
      the cell permeable cyclic GMP analogue, Br-cGMP (0.3-1.0 x 10(-3) M) reduced tube
      formation. 4. The inhibitors of NO synthase, NG-monomethyl-L-arginine (L-NMMA)
      (3.8-102 nmol/disc) and NG-nitro-L-arginine methylester (L-NAME) (1.3-34.2
      nmol/disc) stimulated angiogenesis in the CAM in vivo, in a dose-dependent
      fashion. D-NMMA and D-NAME on the other hand had no effect on angiogenesis in
      this system. 5. L-Arginine (10.9 nmol/disc), although it had a modest
      antiangiogenic effect by itself, was capable of abolishing the angiogenic effects
      of L-NMMA (34.2 nmol/disc) and of L-NAME (3.8 nmol/disc). 6. Dexamethasone, an
      inhibitor of the induction of NO synthase, at 0.2-116.1 nmol/disc, stimulated
      angiogenesis in the CAM, whereas at 348.4-1161 nmol/disc it inhibited this
      process. Combination of 38.7 nmol/disc dexamethasone with L-NAME (9.3 nmol/disc)
      resulted in a potentiation of the angiogenic effect of the former. It appears
      therefore that both the constitutive and the inducible NO synthase may contribute
      to the NO-mediated inhibition of angiogenesis. 7. Superoxide dismutase (SOD),
      which prevents the destruction of NO, at 300 i.u./disc had a modest
      antiangiogenic effect in the CAM, by itself. In addition, SOD, prevented alpha
      thrombin (6.7 nmol/disc) and PMA (0.97 nmol/disc) from stimulating angiogenesis
      in the CAM.8. These results suggest that NO may be an endogenous antiangiogenic
      molecule of pathophysiological importance.

PMID- 7517333
TI  - Inhibition of nitric oxide synthase does not block the development of
      sensitization to the behavioral activating effects of amphetamine.
AB  - Pretreatment with the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine
      methyl ester (L-NAME), a competitive blocker of NO production, did not interfere
      with the development of sensitization to the behavioral activating effects of
      amphetamine (AMPH). On five pre-exposure sessions, at 3-day intervals, rats were
      given two i.p. injections, either 50 mg/kg L-NAME 30 min prior to 1.5 mg/kg D
      AMPH sulfate, saline and AMPH, L-NAME and saline, or saline only. L-NAME reduced
      the levels of activity recorded during the pre-exposure session but had no effect
      on the degree of sensitization shown to a challenge injection of 0.5 mg/kg AMPH
      given 10 days later. A separate study using in vivo microdialysis showed that
      pretreatment with L-NAME did not alter AMPH-stimulated dopamine release in
      nucleus accumbens.

PMID- 7517335
TI  - [Regionalization of the expression of tenascin as a response to the inducers of
      mesoderm].
AB  - Tenascin (TN) is an extracellular matrix (ECM) glycoprotein which possesses
      antiadhesive properties and thus is able to modulate cell interactions with
      molecules of the ECM. In Xenopus embryos, TN is expressed dorsally in a very
      restricted pattern. We have studied the distribution of TN mRNA in tailbud-stage
      embryos by in situ hybridization. We show that TN transcripts are principally
      expressed in myotome cells. No TN mRNA could be detected in lateral plate
      mesoderm. This had led us to study TN expression in response to mesodermal
      inducers. Analysis of the distribution of TN after mesodermal induction of
      blastula animal caps with activin A and bFGF or after ectopic expression of XBra
      shows that TN expression is elicited when dorsal or posterior structures are
      formed. Our results show that TN regionalization in Xenopus embryos depends on
      mesoderm patterning.

PMID- 7517336
TI  - [Expression of cytokine messenger RNA in mice in physiological conditions].
AB  - The expression of the cytokine genes was studied under physiological conditions
      in normal adult mice using RT-PCR method capable of detecting low levels of mRNA.
      Total RNA was prepared from brain, spinal cord, lung, spleen, liver and kidney of
      6 to 8 week-old specific pathogen-free BALB/c mice by acid guanidinium
      thiocyanate-phenol-chloroform (AGPC) method. cDNA was synthesized by M-MLV
      reverse transcriptase, and amplified using the specific oligonucleotide primers
      for IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, IFN-beta and IFN
      gamma by PCR method. Although IL-1 mRNA was detected in all the organs, IL-3 mRNA
      was not detected in any organs tested. IL-2 or IL-4 mRNA and IL-5 mRNA were
      produced only in spleen and lung, respectively. However, IL-6, TNF-alpha and IFN
      mRNA were detected in some different organs. These results suggest that many
      kinds of cytokine mRNA were produced in vivo under physiological conditions in
      normal mice.

PMID- 7517329
TI  - Species-dependent functional properties of non-NMDA receptors expressed in
      Xenopus laevis oocytes injected with mammalian and avian brain mRNA.
AB  - 1. Species-dependent variation in the functional properties of non-NMDA receptors
      was investigated by intracellular recording in Xenopus laevis oocytes injected
      with rat, chick and calf brain mRNA. 2. In all mRNA-injected oocytes, kainic acid
      (KA), domoic acid (Dom) and 5-bromowillardiine (BrW) evoked large, maintained
      membrane currents, in contrast to the smaller, desensitizing responses elicited
      by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic
      acid (QA) and L-glutamic acid (L-Glu). Dose-response curves for KA in oocytes
      injected with calf (EC50 = 96.4 +/- 12.3 microM; mean +/- s.e. mean), chick (87.0
      +/- 8.9 microM) or rat (88.7 +/- 4.3 microM) brain mRNA were similar. 3. Current
      voltage (I-V) relationships determined with KA inwardly rectified in oocytes
      injected with calf or chick mRNA; whereas, outward rectification was observed in
      oocytes injected with rat brain mRNA. 4. In oocytes injected with rat brain mRNA,
      AMPA antagonized responses evoked by KA in a competitive manner. The absolute
      amplitudes of KA and AMPA responses in the same oocytes were significantly
      correlated, which is consistent with both agonists acting on the same receptor
      ionophore complex. 5. In contrast, in oocytes injected with calf or chick brain
      mRNA, AMPA (QA and L-Glu) antagonized the response evoked by KA in a non
      competitive manner. The response amplitudes of KA compared to AMPA, QA or L-Glu
      in the same oocytes were not correlated suggesting discrete receptor-ionophores.
      6. This study favours the existence of distinct non-NMDA receptor subtypes that
      are equi-sensitive to KA. The expressed receptors from different species of mRNA
      may be distinguished by their voltage sensitivities and the type of antagonism
      exerted by AMPA on KA-activated responses. Our observations may reflect further
      heterogeneity of non-NMDA receptors in the central nervous system of different
      vertebrate species.

PMID- 7517337
TI  - [Effects of toxins, apamine, charybdotoxin and iberiotoxin on the relaxation of
      the smooth muscular fiber induced by imidazo(1,2-a)pyrazine derivative].
AB  - Experiments have been performed in order to analyse the mechanism whereby SCA40,
      a new imidazo[1,2-a]pyrazine derivative relaxes airway smooth muscle. We
      investigated the effect of different toxins, known to be K(+)-channel blockers on
      guinea-pig smooth muscle relaxant activity of SCA40. The small conductance Ca(2+)
      activated K(+)-channel blocker apamin (100 nM) did not antagonize the relaxant
      activity of SCA40 in 1 microM carbachol-contracted isolated guinea pig trachea.
      The large conductance Ca(2+)-activated K(+)-channel blocker, iberiotoxin (30, 60
      and 180 nM) antagonized the relaxant activity of SCA40 in an apparently
      competitive manner. The concentration-relaxation curves to SCA40 were shifted to
      the right with no significant alteration in the maximum response. The relaxant
      activity of SCA40 in 1 microM carbachol-contracted isolated trachea was
      antagonized by both charybdotoxin (60 nM) and iberiotoxin (60 nM), but the
      antagonism induced by iberiotoxin appears to be more potent than that induced by
      charybdotoxin. It is concluded that the potent relaxant activity of SCA40 on
      guinea-pig airway smooth muscle in vitro involves a charybdotoxin and iberiotoxin
      sensitive K(+)-channel.

PMID- 7517338
TI  - [Induction of messenger RNA of cytokines by Herpes simplex virus infection in
      mice].
AB  - The induction of the cytokine mRNA after infection with Herpes simplex virus
      (HSV) was studied using RT-PCR method capable of detecting low levels of mRNA.
      Total RNA was prepared from spleen lymphocytes 3 h after infection with HSV-1
      (+GC virulent variant and -GCr attenuated variant of Miyama strain) by acid
      guanidinium thiocyanate-phenol-chloroform (AGPC) method. cDNA was synthesized by
      M-MLV reverse transcriptase, and amplified using the specific oligonucleotide
      primers for IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, IFN-beta
      and IFN-gamma by PCR method. After HSV-1 infection, IFN-alpha, IFN-beta, IFN
      gamma, IL-1 beta, IL-4, IL-6 and TNF-alpha mRNA were significantly induced, but
      IL-2, IL-3 and IL-5 mRNA were not induced. Although IFN-alpha, IFN-gamma and IL-6
      mRNA were more strongly induced by infection with +GC virulent variant than -GCr
      attenuated variant, there was no significant difference in the expression of
      other cytokine mRNA between two variants. These results demonstrate that cytokine
      mRNA in addition to IFN was induced by HSV infection, and suggest that cytokines
      as well as IFNs may play a role in the defense mechanism against HSV infection.

PMID- 7517339
TI  - Identification of Clavibacter michiganensis subsp. sepedonicus using the
      polymerase chain reaction.
AB  - From the sequence of a subcloned DNA fragment of a highly conserved plasmid of
      Clavibacter michiganensis subsp. sepedonicus a pair of oligonucleotides were
      devised for use as polymerase chain reaction primers. The primer sequences do not
      show significant homology with any other sequence deposited in public databases.
      Polymerase chain reactions carried out using this primer pair and untreated cells
      of all strains of C. michiganesis sepedonicus tested resulted in the
      amplification of a DNA fragment of about 670 base pairs. No amplification was
      observed when bacteria belonging to other species were submitted to polymerase
      chain reaction under the same conditions. The detection limit of the assay was 4
      x 10(3) bacteria.

PMID- 7517340
TI  - The connection between the nuclei of binucleated hepatocytes: an ultrastructural
      study.
AB  - Hepatocytes commonly have double nuclei and polyploidy. Both increase with age.
      The relationship of the double nuclei to each other has never been investigated
      at the ultrastructural level. Using a newly developed extraction and embedding
      technique we observed that the two nuclei were often linked by connecting DNA
      strands which span the gap between the two nuclei. The DNA nature of these
      filaments was determined by digestion with DNase. Artifactual intermolecular
      disulfide bonds were prevented by the employment of iodoacetamide in the
      extracting medium. It was further shown that partially fused and/or separated
      nuclei were observed by phase microscopy of living cultures as well as in fixed
      liver tissue. The results may indicate that one way in which binucleation occurs
      is through nuclear separation when the nucleus contains multiples of DNA
      (polyploid).

PMID- 7517342
TI  - In vitro TNF-alpha production and in vivo alteration of TNF-alpha RNA in mouse
      peritoneal macrophages after treatment with different bacterial derived agents.
AB  - Since muramyl dipeptide (MDP) was recognized as a potent monocyte/macrophage
      activating agent, many MDP analogues were synthesized and tested for their
      ability to augment the host immune defence system against neoplasms. This study
      was performed to determine whether the newly synthesized desmuramyl N-acyl
      dipeptides LK 409 and LK 410 were also capable of affecting the immune system.
      For this purpose, the peritoneal macrophages were incubated in vitro with these
      two agents and TNF-alpha production was measured. In addition, the effect of LK
      409 and LK 410 on TNF-alpha and IL-1 RNA levels in in vivo stimulated macrophages
      was determined by quantitative polymerase chain reaction (RT-PCR). None of the LK
      409 and LK 410 concentrations tested were able to render macrophages in vitro to
      excrete a detectable amount of TNF-alpha in the supernatant fluid. However, the
      TNF-alpha and IL-1 RNA levels in macrophages of in vivo treated mice (C57Bl/6)
      were increased in comparison to mock-treated mice. The results indicate that LK
      409 and LK 410 are capable of inducing an increase in TNF-alpha and IL-1 RNA
      levels, yet in vitro TNF-alpha production remains under detectable levels (40
      U/ml).

PMID- 7517343
TI  - Membrane ion channels and cardiovascular ATP-sensitive K+ channels.
AB  - Ion channels are the primary target for a variety of clinically important drugs
      including local anesthetic, antihypertensive, antianginal, antiarrhythmic,
      antidiabetic, anticonvulsant hypnotic and anxiolytic agents. Ion channels are
      specialized proteins inserted in the ion-impermeable cellular membrane, which
      have a water-filled pore permitting the selective passage of a few biologically
      important ions (Na+, K+, Ca++ and Cl-) across the membrane. Multiple channels for
      a given ion can co-exist on the same cell where they have specific functions. The
      flow of ions through channels produces electrical currents which often act as
      biological messengers to change and modulate the functional state of the cell.
      Thus, the influx of Na+ and Ca++ are activating signals whereas the exit of K+
      drives the activated cell to a resting state or strengthen the resting state.
      Interestingly, K+ channels are the most diverse group of ion channels. At least 9
      families of K+ channels co-exist in cardiac myocytes where they regulate the
      heart repolarization and excitability processes under physiological and
      pathological conditions. ATP-sensitive K+ channels of cardiac myocytes are of
      particular interest since they have a very high membrane density and are closed
      under normoxic conditions, becoming operational during ischemic stress when the
      intracellular levels of ATP decline. Their major function has been proposed to be
      the preservation of viability of the myocyte during ischemia. ATP-sensitive K+
      channels are also present in other tissues, such as the blood vessels, where
      their opening causes strong relaxing effects. Cardiac and vascular ATP-sensitive
      K+ channels are the primary target of a novel class of drugs, called K+ channel
      openers, such as nicorandil and aprikalim.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517341
TI  - Kupffer cell/tumor cell interactions and hepatic metastasis in colorectal cancer.
AB  - The degree of interaction with Kupffer cells of two moderately well
      differentiated cell lines, CX-1 and CCl-188 of high metastatic potential (61%)
      were compared to two poorly differentiated cell lines, MIP-101 and Clone A of low
      metastatic potential (6%) in the intrasplenic injection model for liver
      metastasis. MIP-101 and Clone A bound significantly better to mouse Kupffer cells
      in vitro than either CX-1 or CCL-188. We also identified specific cell surface
      proteins mediating attachment of colorectal carcinoma cells to murine Kupffer
      cells. Kupffer cells were radiolabelled and their surface proteins incubated with
      MIP-101 and CX-1. Two radiolabelled proteins from murine Kupffer cells of 14 and
      34 kDa were identified consistently binding to the tumor cells. Binding of both
      proteins was inhibited by asialofetuin but not by fetuin. This suggests that the
      major binding proteins between Kupffer cells and colorectal cancer cells are
      galactose binding lectins.

PMID- 7517345
TI  - Palliative versus curative beliefs regarding tropical epilepsy as a function of
      traditional and medical attributions.
AB  - Although epilepsy may be successfully managed with appropriate medication, in
      Africa epileptics are often vilified, sometimes because of traditional beliefs
      about the illness. We investigated the strength of beliefs which 112 rural
      Malawians held regarding traditional and medical explanations for the cause,
      treatment and cure of epilepsy. Those who believed in traditional causes of
      epilepsy also endorsed traditional treatment for it, though they did not see such
      treatment as curative. Those who believed in a medical treatment, did however see
      such treatment as curative. Knowledge of a local medical facility for the
      treatment of epilepsy was also positively related to the belief that epilepsy is
      curable. The ability of people to simultaneously hold medical and traditional
      beliefs about epilepsy was noted.

PMID- 7517344
TI  - Cytokeratin 18 is an M-cell marker in porcine Peyer's patches.
AB  - The intermediate filaments of the dome epithelium of porcine Peyer's patches were
      studied by immunohistochemistry. The labelling patterns of monospecific
      antibodies directed against cytokeratins 8, 18 and 19 differed considerably.
      About 40% of the dome epithelial cells were intensely labelled by three different
      anti-cytokeratin 18 antibodies, indicating that large amounts of cytokeratin 18
      are present in these cells. In order to verify that these cytokeratin-18
      immunoreactive cells were M-cells, uptake studies using fluorescein-labelled
      yeast particles were performed. Numerous yeast particles were found exclusively
      in dome epithelial cells that were highly positive for cytokeratin 18, thus
      representing M-cells. In contrast, the content of cytokeratin 19 in M-cells was
      lower than that in neighbouring enterocytes. The labelling intensity of
      cytokeratin 8 did not differ between M-cells and enterocytes. In addition, the
      absence of vimentin and desmin from the dome epithelium of porcine Peyer's
      patches was demonstrated. The results show (1) that porcine M-cells differ from
      enterocytes in the composition of their cytoskeleton, (2) that cytokeratin 18 is
      a useful marker for detecting porcine M-cells and (3) that this marker directly
      correlates with M-cell function.

PMID- 7517346
TI  - Inhibitory effects of (4-alkoxy-2, 3, 6-trimethylphenyl) glycopyranosides on
      histamine release induced by antigen-antibody reaction.
AB  - The inhibitory effects of newly synthesized 4-alkoxy-2, 3, 6-trimethylphenyl D
      glycopyranosides on histamine release induced by antigen-antibody reaction were
      examined. Among the compounds tested, 4-hexoxy-2, 3, 6-trimethylphenyl alpha-D
      mannopyranoside exhibited the strongest inhibitory effect. Furthermore, 4-hexoxy
      2, 3, 6-trimethylphenyl alpha-D-glucopyranoside and alpha-D-galactopyranoside
      markedly inhibited antigen-induced histamine release, and their activities were
      more potent than those of the corresponding beta-anomers. These results suggest
      that these compounds may possess excellent anti-allergic activities.

PMID- 7517349
TI  - Mechanism of bradycardia-dependent appearance of manifest extrasystoles in
      concealed ventricular trigeminy.
AB  - A man with ventricular extrasystoles is described. To our knowledge, this is the
      first report of bradycardia dependent appearance of manifest extrasystoles in
      concealed trigeminy. The mechanism was satisfactorily explained, using the
      concepts of longitudinal dissociation and concealed 3:2 Wenckebach periodicity in
      the reentrant pathway of extrasystoles.

PMID- 7517348
TI  - Polyclonal in vitro T cell proliferation and T cell-dependent B cell
      differentiation supported by activated autologous B cells.
AB  - Although anti-CD3-induced T cell proliferation and T cell-dependent B cell
      differentiation are not supported well by resting (nonactivated) B cells as AC,
      human peripheral blood B cells activated in vitro with SAC, rIL2, or anti-IgM
      effectively subserve AC function in a manner qualitatively similar to that of
      blood monocytes and support polyclonal anti-CD3-driven T cell-dependent B cell
      differentiation. Physical contact among T cells, responder B cells, and
      (irradiated) activated B cells is required, and the ability of activated B cells
      to support anti-CD3-driven generation of IgSC parallels surface B7 expression by
      the activated B cells. The fusion protein CTLA4Ig, which binds to B7 and B7-like
      molecules with high avidity and disrupts the interaction of T cell surface CD28
      with B7, inhibits B cell differentiation in a dose-dependent fashion, whereas a
      control fusion protein has no such effect. Thus, activated B cells support
      polyclonal T cell-dependent B cell differentiation via a CD28 (CTLA4)/B7 (B7
      like)-dependent mechanism.

PMID- 7517350
TI  - Self-expanding stents in the treatment of tracheobronchial obstruction.
AB  - The self-expandable stainless steel stents (Gianturco, William Cook, Bjaeverskov,
      Denmark) used extensively in biliary ducts and the vascular system have recently
      been modified for use in the tracheobronchial tree. Between March 1991 and
      September 1992, six patients with unresectable tracheobronchial and mediastinal
      diseases were treated with the placement of one or more self-expanding stents
      under direct vision with a fiberoptic bronchoscope. All patients had been
      intubated for severe respiratory insufficiency. In all cases, immediate relief of
      respiratory symptoms was achieved and all patients were extubated 1 or 2 days
      after stent placement. Tolerance of the stents was excellent. No patient
      complained of pain, discomfort, or foreign body sensation. No infection or
      obstruction of the stents was observed. The chest roentgenogram and the
      bronchoscopies performed during follow-up have shown no change in the position of
      the stents. Our results seem promising since these devices provide effective
      palliation of airway obstructions and are well tolerated.

PMID- 7517347
TI  - Cell adhesion molecule expression within the microvasculature of human colorectal
      malignancies.
AB  - In situ expression of intercellular adhesion molecule-1 (ICAM-1), endothelial
      leukocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1
      (VCAM-1) was investigated in 20 human colorectal cancers using
      immunohistochemical techniques. Tumor microvessels, detected with endothelial
      marker Ulex Europaeus Agglutinin-I (UEAI), were consistently present within both
      stromal and glandular areas. Vessels expressing cell adhesion molecules (CAMs)
      were less frequent but more common within the tumor stroma. Although ICAM-1 and
      ELAM-1 vessel staining was present in all tumors, ICAM-1 staining was the most
      consistent with primary localization to stroma while ELAM-1 was variable with
      localization to both stroma and glandular areas. VCAM-1 staining was inconsistent
      and was rare in glandular areas. A significant increase in the number of vessels
      expressing CAMs with a concomitant decrease in the total number of vessels was
      noted in bowel muscularis adjacent to tumor compared to remote bowel. No
      relationship between number of vessels or frequency of CAM positive vessels and
      tumor site, grade, or stage was noted. These studies demonstrate enhanced
      microvascular expression of CAMs in close proximity to colorectal tumors despite
      decreases in total number of vessels, suggesting that factors within the tumor
      microenvironment effect tumor microvascular development. Correlation between
      these studies and previous microscopic studies suggest that vessels expressing
      CAMs play a role in immune cell infiltration and may provide new targets for anti
      tumor therapies.

PMID- 7517353
TI  - Trends in auto emissions and gasoline composition.
AB  - The invention of the spark-ignited internal combustion engine provided a market
      for a petroleum middle distillate, gasoline, about 100 years ago. The internal
      combustion engine and gasoline have co-evolved until motor vehicles now annually
      consume about 110 billion gallons of gasoline in the United States. Continuing
      air pollution problems and resulting regulatory pressures are driving the need
      for further automotive emissions reductions. Engine and emissions control
      technology provided most earlier reductions. Changing the composition of gasoline
      will play a major role in the next round of reductions. The engineering and
      regulatory definition of a reformulated gasoline is proceeding rapidly, largely
      as the result of an auto and oil industry cooperative data generation program. It
      is likely that this new, reformulated gasoline will be introduced in high-ozone
      regions of the United States in the mid-1990s. Alternative clean fuels, primarily
      methane, methanol, and liquid petroleum gas, will become more widely used during
      this same period, probably first in fleet operations.

PMID- 7517351
TI  - Alpha 2u-globulin nephropathy: review of the cellular and molecular mechanisms
      involved and their implications for human risk assessment.
AB  - This paper reviews what is known about the induction of alpha 2u-globulin
      nephropathy and carcinogenesis. This unique male-rat-specific disease is
      associated with exposure to an ever-increasing number of chemicals. The processes
      leading to nephropathy and renal cancer are among the best-understood mechanisms
      for nongenotoxic chemicals and strongly support that it is a male-rat-specific
      process that is not relevant for human risk assessment. Nevertheless, the data
      available for individual chemicals vary greatly. This necessitates a case-by-case
      analysis of the available data when determining the relevance for humans of this
      chemically induced renal disease in male rats.

PMID- 7517352
TI  - Interpretation of male rat renal tubule tumors.
AB  - Based on an analysis of recent scientific studies, a Technical Panel of the U.S.
      Environmental Protection Agency's (EPA) Risk Assessment Forum recently advised
      EPA risk assessors against using information on certain male rat renal tubule
      tumors to assess human risk under conditions specified in a new Forum report.
      Risk assessment approaches generally assume that chemicals producing tumors in
      laboratory animals are a potential cancer hazard to humans. For most chemicals,
      including classical rodent kidney carcinogens such as N-ethyl-N
      hydroxyethylnitrosamine, this extrapolation remains appropriate. Some chemicals,
      however, induce accumulation of alpha 2u-globulin (alpha 2u-g), a low molecular
      weight protein, in the male rat kidney. The alpha 2u-g accumulation initiates a
      sequence of events that appears to lead to renal tubule tumor formation. Female
      rats and other laboratory mammals administered the same chemicals do not
      accumulate low molecular weight protein in the kidney, and they do not develop
      renal tubule tumors. Because humans appear to be more like other laboratory
      animals than like the male rat, in this special situation, the male rat is not a
      good model for assessing human risk. The Forum report stresses the need for full
      scrutiny of a substantial set of data to determine when it is reasonable to
      presume that renal tumors in male rats are linked to a process involving alpha 2u
      g accumulation and to select appropriate procedures for estimating human risks
      under such circumstances.

PMID- 7517354
TI  - cDNA cloning and deduced amino acid sequence of two ferritins: soma ferritin and
      yolk ferritin, from the snail Lymnaea stagnalis L.
AB  - Pulmonate freshwater snails contain two different ferritin types, soma ferritin
      and yolk ferritin. A cDNA library was constructed from midgut gland poly(A)-rich
      RNA of the snail Lymnaea stagnalis L. and recombinant clones encoding both
      ferritin types were obtained by immunoscreening. The longest cDNA inserts had a
      length of 859 bp (soma ferritin) and 1548 bp (yolk ferritin) and the specificity
      of these inserts was confirmed by immunoprecipitation of both ferritin types
      translated in vitro from hybrid-selected mRNAs. The 5' untranslated region (UTR)
      of the soma ferritin mRNA contains a 28-bp element which shows 64% sequence
      identity with the iron-responsive element (IRE) of vertebrate ferritin mRNAs. The
      soma ferritin mRNA is strongly translated in the wheat germ system but poorly
      translated in rabbit reticulocyte lysate. The yolk ferritin mRNA, which contains
      no IRE, is equally well translated in both in vitro translation systems. The
      deduced amino acid sequence of the soma ferritin subunit (174 amino acid
      residues, M(r) 20140) shows 50-70% sequence identity with subunits of vertebrate
      ferritins. After removal of an 18-amino-acid-residue signal sequence the deduced
      protein sequence of yolk ferritin contains 221 amino acids (M(r) 25438). Sequence
      identity of this chain with other eukaryotic ferritin chains is only 31-42%. Both
      snail ferritin sequences are more similar to the H-subunit type of vertebrate
      ferritins than to the L-type and both have the H-specific amino acid residues of
      the ferroxidase centre. The yolk ferritin sequence has a 42-amino-acid-residue
      insertion predicted to reside in the L loop of the subunit.

PMID- 7517355
TI  - Effect of low pH and heparin on the structure of acidic fibroblast growth factor.
AB  - Changes in the fluorescence of the single tryptophan of acidic fibroblast growth
      factor have been used to monitor the effect of low pH on the conformation of the
      molecule, and the consequences of heparin binding and high ionic strength under
      such conditions. These studies demonstrate that the conformation of the protein
      changes reversibly below pH 5, and that heparin, depending on the conditions, may
      either prevent that change or induce a new irreversible modification of the
      structure, which runs parallel to the partial inactivation of the protein. It is
      also demonstrated that secondary heparin-binding sites appear at low pH, which
      favor the formation of precipitates at some protein/heparin ratios. Precipitation
      and inactivation of fibroblast growth factor at low pH may hinder its wound
      healing activity, since acidification seems frequent in wounds.

PMID- 7517357
TI  - Neutralizing monoclonal antibodies define two different functional sites in human
      interleukin-4.
AB  - Human interleukin-4 (IL-4) is a small four-helix-bundle protein which is
      essential for organizing defense reactions against macroparasites, in particular
      helminths. Human IL-4 also appears to exert a pathophysiological role during
      various IgE-mediated allergic diseases. Seven different monoclonal antibodies
      neutralizing the activity of human IL-4 were studied in order to identify
      functionally important epitopes. A collection of 41 purified IL-4 variants was
      used to analyse how defined amino acid replacements affect binding affinity for
      each individual mAb. Specific amino acid positions could be assigned to four
      different epitopes. mAbs recognizing epitopes on helix A and/or C interfered with
      IL-4 receptor binding and thus inhibited IL-4 function. However, other mAbs also
      inhibiting IL-4 function recognized an epitope on helix D of IL-4 and did not
      inhibit IL-4 binding to the receptor protein. One mAb, recognizing N-terminal and
      C-terminal residues, partially competed for binding to the receptor. The results
      of these mAb epitope analyses confirm and extend previous data on the functional
      consequences of the amino acid replacements which showed that amino acid residues
      in helices A and C of IL-4 provide a binding site for the cloned IL-4 receptor
      and that a signalling site in helix D interacts with a further receptor protein.

PMID- 7517358
TI  - A liquid-phase binding analysis for L-selectin. A strong dependency on highly
      clustered sulfate groups.
AB  - L-selectin, together with E- and P-selectins, forms a newer group of cell
      adhesion molecules which are believed to interact with carbohydrate ligands
      [Lasky, L. A., Singer, M. S., Yednoch, T. A., Dowbenko, D., Fennie, C.,
      Rodriguez, H., Nguyen, T., Stachel, S. & Rosen, S. D. (1989) Cell 56, 1045-1055].
      Using radiolabeled fucoidan as a reference ligand, we have developed a new liquid
      phase microcentrifugation assay where fine differences in binding affinity can be
      compared accurately. We found that glucan sulfates strongly inhibited the binding
      of fucoidan by murine L-selectin-IgG chimera. The efficacy of inhibition is
      extremely dependent on the size (up to 12 kDa) and the sulfate density (up to two
      sulfate groups/glucose molecule) of the glucan sulfates. The nature of the inter
      glucose linkages is also important. These data suggest that the binding by L
      selectin prefers certain clustering and proper spatial arrangement of the anionic
      groups.

PMID- 7517356
TI  - Determination of membrane-bound fragments of cytochrome P-450 2B4.
AB  - Membrane-bound sites of cytochrome P-450 2B4 (LM2) were determined by means of
      two different methods, photoactivated binding of membrane phospholipids to the
      protein and epitope mapping by antibodies. Phospholipids bearing photoreactive
      labels at different distances from the their polar 'head' were used in the former
      case. Phosphatidylcholine labelled at the apolar end of the fatty acid chain
      bound only to the N-terminal region of the hemoprotein. Other phospholipids
      labelled nearer to the head group bound not only to the N-terminus but also to
      the segments 273-314 and 427-491. Epitope mapping of the domain next to the N
      terminus (residues 21-119) of the isolated hemoprotein was performed with the
      help of a peptide-scanning method, a programmable peptide synthesis on pins
      followed by ELISA testing with the polyclonal antiserum against cytochrome P-450
      2B4. This domain was shown to possess a considerable density of sites with high
      antigenic activity. No membrane-penetrating part of this domain was found except
      for the fragment 1-21. A model of structure of P-450 2B4 was computed by
      comparison with the structure of cytochrome P-450cam on the basis of an alignment
      of 47 cytochromes P-450 with the former hemoprotein. Major parts of the protein
      sequences photoreacting with the phospholipid probes, but not the antibody
      reactive epitopes of the region 21-119, are located at the membrane-facing side
      in this model.

PMID- 7517359
TI  - Induction of B cell costimulatory function by recombinant murine CD40 ligand.
AB  - T cell-dependent regulation of B cell growth and differentiation involves an
      interaction between CD40, a B cell surface molecule, and the CD40 ligand (CD40L)
      which is expressed on activated CD4+ T cells. In the current study, we show that
      recombinant membrane-bound murine CD40L induces B cells to express costimulatory
      function for the proliferation of CD4+ T cells. CD40L- or lipopolysaccharide
      (LPS)-activated, but not control-cultured B cells were strong costimulators of
      anti-CD3 or alloantigen-dependent T cell responses. The molecular interactions
      responsible for the increased costimulatory functions were examined by analyzing
      the activated B cells for changes in the expression of two costimulatory
      molecules, B7 and heat-stable antigen (HSA), as well as by the use of antagonists
      of B7 and HSA (CTLA4.Fc and 20C9, respectively). The expression of both B7 and
      HSA was enhanced on B cells activated with LPS. As observed in previous studies,
      the costimulatory activity of the LPS-activated B cells was dependent on both B7
      and HSA and was completely inhibited in the presence of a combination of CTLA4.Fc
      and 20C9. In contrast, activation of B cells with CD40L induced the expression of
      B7 but did not enhance the expression of HSA. In addition the costimulatory
      activity of the CD40L-activated B cells was partially, but not completely,
      inhibited by the combination of CTLA4.Fc and 20C9. These results demonstrate that
      CD40L regulates costimulatory function of B cells in part by inducing the
      expression of B7 and suggest that CD40L-activated B cells express an additional
      costimulatory activity that is not associated with LPS-activated B cells.

PMID- 7517361
TI  - Skin disease-related T cells bind to endothelial selectins: expression of
      cutaneous lymphocyte antigen (CLA) predicts E-selectin but not P-selectin
      binding.
AB  - Cutaneous lymphocyte antigen (CLA), defined by the HECA-452 antibody, is a cell
      surface glycoprotein found on a subset of T cells in peripheral blood that binds
      specifically to E-selectin. This marker is present on the majority of T cells at
      sites of cutaneous inflammation and immune responses. Based upon such evidence,
      an association between T cell CLA expression and skin homing has been proposed.
      To understand better this relationship, we asked whether putative disease
      related, antigen-specific T cells expressed CLA. In this study, we employed T
      helper type 2 (TH2) T cell clones specific for house dust mite (Dermatophagoides
      pteronyssinus) antigens. These cells were derived from challenged skin of an
      individual known to react positively to epicutaneous challenge with this agent.
      In this study, we show that these cloned T cells showed very high homogeneous
      expression of CLA (nearly 500-fold higher than T cell clones derived from
      peripheral blood) and bound specifically to recombinant E-selectin. The CLA
      molecule on these cells was identified not only by HECA-452, but also by CSLEX-1,
      indicating that it contained sialyl-Le(x) (S-Le(x)) determinants. T cells cloned
      under similar conditions from peripheral blood were CLA negative or low and bound
      poorly to E-selectin. Surprisingly, both skin and blood clones bound comparably
      to P-selectin. This binding was independent of S-Le(x) or CLA expression. We
      conclude that in sensitized individuals, antigen-specific T cells expressing high
      levels of CLA localize in skin promptly after epicutaneous challenge. This
      localization is likely to involve the interaction of S-Le(x) determinants on the
      CLA molecule with E-selectin on the dermal microvasculature. We further conclude
      that T cells can interest with P-selectin on endothelium and that S-Le(x) does
      not appear to be necessary for this interaction.

PMID- 7517360
TI  - B cells from CBA/N mice do not proliferate following ligation of CD40.
AB  - The CBA/N mouse carries the X-linked immunodeficiency xid, resulting in defective
      B cell development. B cells from these animals cannot mount antibody responses to
      type 2 T-independent antigens, and do not synthesize DNA when stimulated with
      anti-immunoglobulin (Ig) antibodies which are mitogenic for normal B cells. The
      primary antibody responses of CBA/N mice to T-dependent antigens have also been
      reported to be abnormal. Here we describe the results of experiments which
      demonstrate that the B cells from these animals respond abnormally to ligation of
      CD40, a B cell surface molecule now known to play a key role during T cell-B cell
      interactions, via its interaction with the counterligand (CD40L) expressed by
      activated T cells. Hence, xid B cells fail to proliferate when cultured with
      preactivated T helper type 2 (Th2)T cells (known to express CD40L), with a
      soluble CD40L-CD8 fusion protein, or in response to monoclonal antibodies to
      CD40, even in the presence of IL-4 and/or anti-Ig reagents. However, xid B cells
      do receive abortive activation signals following ligation of CD40, as manifested
      by up-regulation of class II major histocompatibility complex and CD23 antigens.
      Since the xid defect has now been identified as a point mutation in the protein
      tyrosine kinase Btk, our results point to an important role for this kinase in
      the downstream signaling cascade elicited in response to ligation of either
      surface Ig or CD40.

PMID- 7517362
TI  - T cell receptor stimulation, but not CD28 costimulation, is dependent on LFA-1
      mediated events.
AB  - Accessory molecules play a crucial role in the development of the T cell response
      to antigenic challenge. In this manuscript we specifically examine the role of
      two accessory molecules, CD28 and LFA-1, in modulating the T cell proliferative
      response to a variety of stimuli. We demonstrate that the proliferation induced
      by staphylococcal enterotoxins A and B in combination with CD28 costimulation is
      dependent on LFA-1-mediated events. This requirement for LFA-1 is independent of
      T cell-accessory cell adhesion. Similarly, an allogeneic mixed lymphocyte
      reaction, which has previously been shown to be a CD28-dependent response, can be
      inhibited by blockade of LFA-1. This suggests LFA-1 plays an essential role in
      these responses, either by enhancing intercellular adhesion or by an independent
      signal transduction event. In contrast, when the primary activating stimulus is
      delivered by immobilized anti-CD3 antibody or by PMA, and the secondary stimulus
      by either alpha-CD28 or cell-bound CD28 ligand B7, there is no requirement for
      LFA-1. In addition, we demonstrate that cross-linking of LFA-1 with immobilized
      monoclonal antibody, or engagement of LFA-1 with ICAM-1 expressed on the surface
      of a CHO cell, provide an insufficient costimulus for T cell proliferation
      initiated by enterotoxin, immobilized alpha-CD3 or phorbol ester. Our data
      suggests that LFA-1, in contrast to CD28, functions not as a costimulatory
      molecule, but serves primarily to modulate the signal delivered through the T
      cell receptor.

PMID- 7517363
TI  - Development and proliferation of lymphocytes in mice deficient for both
      interleukins-2 and -4.
AB  - Interleukin (IL)-2 and IL-4 are considered as important regulators of growth and
      differentiation of lymphocytes. We report that in mice made deficient for both IL
      2 and IL-4 by gene targeting all major T cell subsets and B cells were normal,
      indicating that IL-2 and IL-4 are not essential for development of the immune
      system. Paradoxically, proliferation of T cells was increased in both IL-2 and IL
      4-deficient homozygous mice.

PMID- 7517365
TI  - Determination of amino acids on agretopes of pigeon cytochrome c-related peptides
      specifically bound to I-A allelic products.
AB  - In our prior study it was demonstrated that residues 46 and 54 on a synthetic
      peptide, AEGFSYTVANKNKGIT (50V), work as an agretope (site contacts with major
      histocompatibility complex molecules) and residues 50 and 52 function as an
      epitope (site contacts with T cell receptor), when tri-molecular complexes are
      formed among 50V,I-Ab and the T cell receptor. 50V was composed of residues 43 to
      58 of pigeon cytochrome c (p43-58) except that the aspartic acid (D) at residue
      50 was substituted by valine (V). Substitution of agretopic residues on 50V
      changed this I-Ab-binding peptide to an I-Ak-binding peptide, suggesting that
      positions 46 and 54 work as an agretope in I-Ak-restricted T cell responses. In
      the present study we examined whether residues 46 and 54 of 50V worked as
      agretopes in T cell responses restricted to other I-A haplotypes. The 50V-related
      peptides with phenylalanine (F) at position 46 and alanine (A) at position 54
      bound tightly to I-Ab, I-Ad, I-Aq and I-As molecules and stimulated T cells most
      potently in mice bearing these I-A haplotypes. In contrast, 50V-related peptides
      carrying D at position 46 and A at position 54 bound most potently to I-Ak
      molecules, and the peptides with arginine (R) at position 46 and A at position 54
      bound most efficiently to I-Av molecules. The present findings, thus, demonstrate
      that the agretopic positions on the p43-58 related peptides are preserved in T
      cell responses restricted to each I-A haplotype studied, and that the specific
      amino acids on the agretopic positions exist a priori for each I-A allele
      specific structure.

PMID- 7517366
TI  - Tyrosine phosphorylation of alpha tubulin in human T lymphocytes.
AB  - N-terminal sequencing of the 55- and 50-kDa polypeptides affinity purified on a
      phosphotyrosine monoclonal antibody column from activated Jurkat T cells
      identified alpha and beta tubulin. Two-dimensional gel analysis indicated that
      alpha tubulin was directly phosphorylated on tyrosine. beta Tubulin was not
      detectably tyrosine phosphorylated but was precipitated by anti-phosphotyrosine
      (PTyr) antibody by virtue of its association with the alpha subunit as a
      heterodimer. Phosphotyrosyl alpha tubulin was not incorporated into intact
      microtubules and was all in the unpolymerized soluble fraction. These results
      suggest that tyrosine phosphorylation of alpha tubulin may inhibit the ability of
      this subunit to polymerize into microtubules. Stimulation of Jurkat T cells via T
      cell receptor increased the amount of tubulin precipitated by the anti-PTyr
      antibody. These data raise the possibility that the polymerization of tubulin
      heterodimers may be regulated by phosphorylation on tyrosine during T cell
      activation.

PMID- 7517367
TI  - Expression, intracellular localization, and gene transcription regulation of the
      secretory protein 7B2 in endocrine pancreatic cell lines and human insulinomas.
AB  - 7B2 is a 23-kDa protein encoded by a single gene that is expressed in a variety
      of neuroendocrine tissues. Although its physiological role has not yet been
      elucidated, its presence in secretory granules suggests a function in the
      secretory machinery of certain neuronal and endocrine cells in various species.
      The present study characterizes the expression of 7B2 in endocrine pancreatic
      cells. We demonstrate that: (i) 7B2 is highly expressed in human insulinomas;
      (ii) its ultrastructural localization, associated with secretory granules of A
      and B cells of the islets, suggests a participation of 7B2 in the secretion of
      insulin and glucagon; (iii) sequences located in the first intron of the 7B2 gene
      are required for its transcription in either insulinoma or glucagonoma cell
      lines; and (iv) in a B cell-like insulinoma cell line, the transcription of 7B2
      is regulated by protein kinase A and protein kinase C activators, while in an A
      like insulinoma cell line, 7B2 gene transcription seems to be constitutively
      activated.

PMID- 7517368
TI  - Rat connexins 30.3 and 31 are expressed in the kidney.
AB  - Six connexin genes have previously been shown to be expressed in the rat kidney.
      Given the structural and functional diversity of the kidney, we hypothesize that
      other connexin genes may be expressed. We have partially screened a rat kidney
      cDNA library using low-stringency hybridization conditions with cDNA probes from
      rCx 43 and rCx 26 and report here the isolation of two connexin cDNA clones, rCx
      30.3 and rCx 31, that have not previously been shown to be expressed in the rat
      kidney. Furthermore, rCx 30.3 utilizes two distinct transcripts in the kidney,
      while rCx 31 utilizes two transcripts in skin but only one in the kidney.

PMID- 7517364
TI  - Professional presentation of antigen by activated human T cells.
AB  - Activated human T cells express class II molecules, but their capacity to present
      soluble antigens and stimulate T cells has been repeatedly questioned. Two lines
      of evidence indicate that T cells may indeed function as professional antigen
      presenting cells. First, T cells that have been recently activated can
      efficiently capture, process and present tetanus toxoid to class II-restricted T
      cell clones. This capacity correlates with the rate of class II synthesis.
      Second, activated T cell clones express high levels of B7, are powerful
      stimulators in mixed lymphocyte reactions, and their stimulatory capacity is
      inhibited by soluble CTLA4 or anti-B7 antibody. Furthermore, expression of B7 can
      be detected in vivo on T cells from biopsies of patients with liver disease.
      Presentation of soluble antigen by activated T cells may play a role in the
      amplification of the specific response, and possibly in immunopathological
      states.

PMID- 7517369
TI  - Modulation of connexins during differentiation of oval cells into hepatocytes.
AB  - The connexins are a family of related gap-junction proteins, implicated in
      embryonic development, cell growth control, and cellular differentiation. To
      identify connexins involved in liver cell differentiation, both in vivo and in
      vitro systems were employed to study expression of connexins 26, 32, and 43.
      Northern blot analysis and in situ hybridization were used to measure the levels
      of connexin expression and cellular localization of the transcripts,
      respectively. Normal liver expressed high connexin 32, low connexin 26, and
      barely detectable connexin 43. In vivo proliferation and differentiation of oval
      cells was at first accompanied by increased connexin 43 and decreased connexin 32
      expression; later as the oval cells differentiated into hepatocytes, connexin 43
      disappeared and connexin 32 increased to control levels. In situ hybridization
      showed that both oval cells and bile duct epithelial cells, but not hepatocytes,
      expressed connexin 43. A switch from connexin 43 to connexin 32 expression was
      observed following in vitro transformation and differentiation of rat liver
      epithelial cells toward the hepatocytic lineage. These results suggest that early
      progenitor cells in the liver express connexin 43 and a switch from connexin 43
      to connexin 32 may signal commitment to hepatocytic differentiation.

PMID- 7517371
TI  - The biochemistry of ancient DNA in bone.
AB  - The amount of DNA in ancient bone was determined by ethidium bromide staining
      after the removal of the potent Taq inhibitor, fulvic acid. A complete
      decalcification and a perfusion protocol were used to recover DNA from bone. A
      variety of purification techniques including molecular sieve, hydroxyapatite
      binding and 'Magic' preparations yielded DNA that spanned from 3.4 micrograms/g
      of bone to below detectable limits. Fulvic acid was shown to interfere with the
      quantification of DNA derived from ancient human skeletal material one hundred to
      over seven thousand years old. Scanning UV in the 300 to 230 nm range is a simple
      and sensitive technique for documenting fulvic acid contamination in ancient bone
      extracts.

PMID- 7517372
TI  - Expression of adhesion molecules in endothelial cells during allogeneic bone
      marrow transplantation.
AB  - Endothelial cell activation during allogeneic bone marrow transplantation, mainly
      in acute graft-versus-host disease (aGvHD) was studied in 23 recipients and 5
      controls using anti-von Willebrand factor (vWF) antibody, antibodies to
      endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion
      molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and anti-HLA
      DQ antibody, by immunohistological staining of skin. vWF extravasation, ELAM-1
      and VCAM-1 expression were present in most recipients with a cutaneous rash which
      was confirmed as an aGvHD by histological examination (documented aGvHD) (p =
      0.005 for vWF extravasation and ELAM-1 expression and p = 0.03 for VCAM-1
      expression in comparison with the controls). In recipients with a rash, the cases
      displaying vWF extravasation and ELAM-1 expression were significantly more
      numerous in those with a documented aGvHD than in those without histological
      features of aGvHD (p = 0.01). vWF extravasation and ELAM-1 occurred concomitantly
      (p < 0.01). This study demonstrates that, during the course of skin aGvHD
      following bone marrow transplantation, there is transient expression of ELAM-1
      and VCAM-1 by endothelial cells and simultaneous vWF extravasation, indicating an
      intense inflammation with endothelial cell participation.

PMID- 7517370
TI  - Separation of phenotypically distinct subpopulations of cultured human retinal
      pigment epithelial cells.
AB  - Like most epithelial cells that are isolated from tissues and placed in culture,
      the phenotype of human retinal pigment epithelial cells (RPE) in vitro is more
      variable than for the same cells in situ. The phenotypic heterogeneity of the
      cultures has been attributed to varying stages of differentiation of the cells
      induced by the culture environment. In this study we show that within the same
      cultures RPE cells exist as phenotypic variants which are distinct and stable.
      Two phenotypically distinct subpopulations were identified, one epithelioid and
      one fusiform, that were present from the first spreading event in primary culture
      through multiple serial passages and when maintained for extended periods at
      confluency. Cell aggregation studies indicated differences in cellular adhesions,
      known determinants of cell shape, between the subpopulations. Methods to separate
      the subpopulations were developed which are based on the differential trypsin
      sensitivity of adhesions. The separated subpopulations had the same RPE
      cytokeratins by immunoblotting, but cytokeratin filaments (and actin filaments)
      had different organizations. The study indicates that RPE cell cultures contain
      at least two subpopulations of phenotypically distinct cells under identical
      culture conditions that can be separated and propagated independently. The
      phenotypic variants offer a model system for investigating determinants of
      epithelial cell shape in RPE. Further, the separation methods might be applied to
      test for phenotypic variants in other types of cultured epithelia.

PMID- 7517374
TI  - Involvement of neurokinin 1 and 2 receptors in viscerosensitive response to
      rectal distension in rats.
AB  - BACKGROUND/AIMS: Tachykinins participate in somatic pain and intestinal motility
      control. The role of tachykinin receptors in both colonic motor disturbances and
      visceral pain (abdominal contractions as an index of visceral pain) induced by
      rectal distension were investigated. METHODS: Rats were surgically prepared with
      electrodes implanted on the proximal colon and the abdominal striated muscles.
      Catheters were implanted in lateral ventricles of the brain. Rectal distension
      was performed by inflation of a balloon (0.1-1.6 mL) rectally inserted. CP-96,345
      and RP-67,580 (neurokinin [NK] 1 antagonists) and SR-48,968 (NK2 antagonist) were
      injected intraperitoneally (IP) or intracerebroventricularly (ICV) 20 minutes
      before distension. GR-73,632 and GR-64,639 (NK1, NK2 agonists) were infused
      intravenously at 0.15 micrograms.kg-1.min-1. RESULTS: Rectal distension evoked a
      significant inhibition of colonic motility and an increase in abdominal
      contractions. CP-96,345 injected ICV (0.2-0.8 mg/kg) or IP (5-10 mg/kg) and RP
      67,580 (0.2 mg/kg IP) eliminated distension-induced colonic inhibition but did
      not affect abdominal response. SR-48,968 did not affect colonic response but
      significantly reduced visceral pain (0.4, 0.8 mg/kg ICV: 5-10 mg/kg IP). GR
      73,632 enhanced the rectal distension-induced colonic inhibition, whereas GR
      64,349 induced a greater abdominal response. CONCLUSIONS: NK1 receptors mediate
      the rectocolonic inhibitory reflex, whereas NK2 receptors participate in visceral
      pain; both responses involve central structures.

PMID- 7517375
TI  - Salmonella typhimurium enterotoxin epitopes shared among bacteria.
AB  - The deduced amino acid sequence of the cloned Salmonella enterotoxin gene (stn)
      was used to prepare anti-peptide antibodies. These antibodies were then employed
      to screen isolates of this enteric pathogen for the synthesis of protein
      enterotoxin (Stn). Cell lysates of all Salmonella isolates tested displayed a
      prominent immunoblot band of approximately 29 kDa, which was consistent with the
      size of the cloned stn gene product. Among other Gram-negative bacteria examined,
      isolates of Klebsiella, Enterobacter, and Citrobacter exhibited a similar-sized
      protein that reacted strongly with the Stn antibodies. Since the stn gene was
      located opposite the hydrogenase regulatory genes (hydHG) required for hydrogen
      metabolism in bacteria, our data suggested that only in Salmonella and some other
      members of the family Enterobacteriaceae had the DNA sequence evolved, presumably
      through point mutations, into an expressed gene product of similar size.

PMID- 7517373
TI  - Acute responses of rat stomach enterochromaffinlike cells to gastrin: secretory
      activation and adaptation.
AB  - BACKGROUND/AIMS: Evidence for gastrin-induced histamine secretion from isolated
      rat enterochromaffinlike (ECL) cells was presented recently. We have investigated
      the gastrin-evoked secretory activation and adaptation of ECL cells in intact
      rats over a time span of a few minutes to several hours. METHODS: Fasted rats
      received a maximally effective dose of synthetic human Leu15-gastrin-17 by
      continuous intravenous infusion. ECL cell ultrastructure and ECL cell-related
      parameters (e.g., mucosal histamine and pancreastatin concentrations, histidine
      decarboxylase [HDC] activity, and messenger RNA [mRNA] concentration) were
      analyzed. RESULTS: Gastrin reduced the number of cytoplasmic vesicles in ECL
      cells while reducing the concentrations of histamine and pancreastatin in the
      oxyntic mucosa. The effects were maximal within a few hours after the start of
      gastrin infusion. The concentration of pancreastatin in serum was elevated for
      the duration of the study. The mucosal concentrations of histamine and
      pancreastatin returned to prestimulation values after 4-6 hours. The HDC activity
      and mRNA concentration increased progressively until after 6-8 hours of gastrin
      infusion. CONCLUSIONS: Gastrin promptly degranulates the ECL cells, releasing
      histamine and pancreastatin from the vesicles. Synthesis of histamine and
      pancreastatin is accelerated, a process associated with renewal of vesicles. The
      increase in HDC activity and mRNA concentration continues for several hours after
      restoration of the vesicles.

PMID- 7517376
TI  - A murine monoclonal antibody directed against a yeast cell wall glycoprotein
      antigen of the yeast genus Saccharomyces.
AB  - Murine monoclonal antibodies (mAbs) were selected against a cell wall
      glycoprotein of Saccharomyces cerevisiae. One of the mAbs (92-276/018)
      specifically identified S. cerevisiae and the sibling species S. paradoxus, S.
      pastorianus and S. bayanus in immunofluorescence studies and immunoblot analyses,
      while no other yeast genera except Saccharomyces were recognized. Further
      analysis indicated that the mAb 92-276/018 reacts with an epitope in the
      carbohydrate chain of the cell wall glycoproteins.

PMID- 7517378
TI  - Is there IgA of gut mucosal origin in the serum of HIV1 infected patients?
AB  - This study was performed in 77 HIV1 seropositive adult patients to characterise
      the IgA hyperglobulinaemia seen in the serum during the course of HIV infection.
      It was shown that both IgA1 and IgA2 subclass concentrations were simultaneously
      increased but the IgA1 increase was predominant. Secretory IgA (SIgA)
      concentration was significantly increased and IgA activity to gliadin, bovine
      serum albumin, and casein could be detected and was correlated with SIgA
      concentration. In contrast, IgA activity to cytomegalovirus and to tetanus toxoid
      did not correlate with total IgA concentration. These data suggest the presence
      of IgA from gut mucosal origin in the serum of these patients. Hyper IgA was
      inversely correlated with the CD4+ cell number. The increase of all parameters
      studied varied according to the total IgA concentration in the serum but was also
      directly related to the stage of immune deficiency in patients with hyper IgA.

PMID- 7517377
TI  - BPH: new guidelines based on symptoms and patient preference. The Agency for
      Health Care Policy and Research.
AB  - Benign prostatic hyperplasia (BPH) is the most common tumor in the aging human
      male. BPH is rarely a life-threatening condition, but it can affect the quality
      of an older man's life when it causes urinary symptoms. Several interventions are
      available for BPH: surgery, most often transurethral resection of the prostate
      (TURP); medication, including alpha blockers and 5-alpha reductase inhibitors;
      and balloon dilation. An appropriate option for many men is no active treatment
      but "watchful waiting." The common nature and cost of BPH and the range of
      available therapies stimulated the development of a guideline by a
      multidisciplinary panel sponsored by the federal Agency for Health Care Policy
      and Research (AHCPR).

PMID- 7517379
TI  - Inflammatory response in the early prediction of severity in human acute
      pancreatitis.
AB  - The role of the inflammatory response in acute pancreatitis and its relation with
      the clinical course was examined. This study examined if the serial measurement
      of polymorphonuclear granulocyte (PMN) elastase/A1PI complex, phospholipase A
      catalytic activity, C reactive protein, and other acute phase proteins, and the
      protease inhibitor alpha 2-macroglobulin, provides meaningful information for
      prognosis. Eighty non-consecutive patients with acute pancreatitis, classified
      according to their clinical outcome into mild (n = 40) and severe pancreatitis (n
      = 40), were followed up daily. Between 48 hours, median values of PMN-elastase, C
      reactive protein--and most of the acute phase proteins--and phospholipase A
      activity, were significantly higher in the severe pancreatitis group. PMN
      elastase shows a dynamic course and it reaches an early peak value at days 1-2,
      followed by C reactive protein (days 2-4) phospholipase A (day 3), and a negative
      peak for alpha 2-macroglobulin (days 4-5). PMN elastase (day 1) and C reactive
      protein (day 2) were selected by discriminant analysis as the most useful
      variables studied to allow the early accurate prediction of severity (sensitivity
      100%, specificity 95%). Little or no predictive additional value was found for
      all other variables studied. These results strongly suggest a close relation
      between inflammatory parameters and clinical course in acute pancreatitis, and
      discriminant analysis of these variables provides a useful method to classify
      severity.

PMID- 7517384
TI  - Diagnostic and clinical implications of the different genotypes of hepatitis C
      virus.

PMID- 7517382
TI  - Effect of obstructive cholestasis on membrane traffic and domain-specific
      expression of plasma membrane proteins in rat liver parenchymal cells.
AB  - We investigated the effect of bile duct ligation and its release on membrane
      traffic and plasma membrane protein distribution in rat hepatocytes.
      Immunofluorescence studies with monoclonal antibodies against six domain-specific
      surface antigens revealed that bile duct ligation leads to an accumulation of
      pericanalicular vesicles containing canalicular antigens. All apical antigens
      could be demonstrated in the basolateral plasma membrane, whereas only one out of
      three basolateral antigens redistributed to the canalicular plasma membrane.
      After release of bile duct ligation, the accumulated pericanalicular vesicles
      disappeared within minutes, whereas the plasma membrane polarity was not restored
      within 1 hr. Monitoring secretion of polymeric IgA and horseradish peroxidase
      into bile demonstrated that bile duct ligation also inhibits the transcytotic
      vesicle pathway and severely impairs the function of tight junctions. In
      contrast, bile duct ligation appears not to affect the endoplasmic reticulum to
      basolateral membrane traffic as assessed by determination of newly synthesized
      albumin and transferrin in serum nor does it influence receptor mediated
      endocytosis at the basolateral plasma membrane.

PMID- 7517383
TI  - Tetrahydroaminoacridine-induced ribosomal changes and inhibition of protein
      synthesis in rat hepatocyte suspensions.
AB  - Tacrine (tetrahydroaminoacridine) is currently the only drug approved for the
      treatment of Alzheimer's disease. Unfortunately, tetrahydroaminoacridine therapy
      is often limited by this drug's propensity to induce reversible hepatotoxicity.
      Using suspensions of freshly isolated rat hepatocytes, we investigated the
      mechanism of tetrahydroaminoacridine cytotoxicity by examining the effect of
      tetrahydroaminoacridine on hepatocyte viability, protein synthesis, protein, DNA
      and RNA levels and ultrastructure. Our experimental findings support the
      explanation that tetrahydroaminoacridine-induced hepatotoxicity results from
      tetrahydroaminoacridine's adverse effect on protein synthesis and ribosomal
      structure and function. We found that viable, tetrahydroaminoacridine-treated
      hepatocytes (1.0 to 2.0 mmol/L or 118 to 235 micrograms/10(6) cells) demonstrated
      a dose-dependent and dramatic aggregation of ribosomes on endoplasmic reticulum
      as well as the aggregation of other nucleic acids found in the nucleus
      (chromatin) and in mitochondria. These electron microscopy data suggest that
      tetrahydroaminoacridine treatment results in severe ribosomal dysfunction. This
      was confirmed by the observed rapid loss of cellular RNA content (but not DNA or
      protein) and the rapid and complete inhibition of protein synthesis in
      tetrahydroaminoacridine-treated cells (lowest concentration tested was 0.5 mmol/L
      or 58 micrograms/10(6) cells). Thus tetrahydroaminoacridine treatment appears to
      aggregate hepatocellular nucleic acids, and in doing so adversely affects
      ribosomal function and protein synthesis. We propose that these adverse effects
      of exposure to tetrahydroaminoacridine are responsible for
      tetrahydroaminoacridine-induced hepatotoxicity.

PMID- 7517380
TI  - A phase II study of high-dose cisplatin, vinblastine, bleomycin, and etoposide
      (PVeBV regimen) in malignant nondysgerminomatous germ-cell tumors of the ovary.
AB  - Fourteen patients with malignant nondysgerminomatous germ-cell tumors of the
      ovary were treated with a combination of high-dose cisplatin, vinblastine,
      bleomycin, and etoposide (PVeBV regimen). Nine patients received PVeBV as primary
      postoperative therapy, of whom four had no residual disease. Four patients
      received PVeBV for recurrent disease. One patient underwent PVeBV therapy as
      second-line treatment. Three patients with initial poor prognostic features were
      treated with early high-dose chemotherapy with autologous bone marrow rescue as
      consolidation therapy after two cycles of PVeBV. Ten of 14 patients (71%) are
      progression-free with a median follow-up of 6 year. Equal efficacy and less
      toxicity favor the combination of bleomycin, etoposide, and cisplatin (BEP) as
      standard treatment of ovarian germ-cell tumors in the 1990s.

PMID- 7517386
TI  - Reverse transcription-polymerase chain reaction detection of transcribed
      sequences on human chromosome 21.
AB  - Seventy-four pairs of oligonucleotides derived from sequence-tagged sites (STSs)
      on the long arm of human chromosome 21, specifically from bands 21q22.1 to
      21q22.3, were used in reverse transcription-polymerase chain reactions (RT-PCR)
      to detect the presence of expressed sequences in a fetal brain. These STSs
      included 69 that had not been related to transcribed sequences and 5 that had
      detected two known genes and three previously isolated cDNA clones. Of the 69
      STSs analyzed in RT-PCR, 25 allowed amplification of specific cDNA fragments. The
      sizes of amplified cDNA fragments match those amplified from either human genomic
      DNA or somatic hybrid cells containing human chromosome 21. Of the 11 cDNA
      analyzed in Northern blot hybridizations, 6 hybridized to specific RNA species.
      The rapid screening for cDNA using previously mapped STSs has provided insight
      into the distribution of expressed sequences in this region of chromosome 21.
      Northern blot analysis of the amplified cDNA fragments has revealed interesting
      candidate genes in two disease loci. The marker D21S267 was previously mapped in
      the Down syndrome region of chromosome 21, and the marker D21S113 is closely
      linked to progressive myoclonus epilepsy. The cDNA fragments amplified using the
      primer sequences derived from D21S267 and D21S113 hybridized to 7- and 6.5-kb
      transcripts, respectively, which seem to express predominantly in brain.

PMID- 7517381
TI  - Mitochondrial dysfunction during anoxia/reoxygenation injury of liver sinusoidal
      endothelial cells.
AB  - Sinusoidal endothelial cell injury plays a pivotal role in anoxia/reoxygenation
      liver damage. However, the mechanisms culminating in anoxia/reoxygenation
      endothelial cell injury remain unclear. Our aims were to determine whether
      anoxia/reoxygenation injury of sinusoidal endothelial cells causes mitochondrial
      dysfunction. In cultured rat liver sinusoidal endothelial cells, the
      mitochondrial membrane potential, cytosolic free calcium and cytosolic pH were
      quantitated by means of fluorescent probes and multiparameter digitized video
      microscopy. Cell viability was measured on the basis of lactate dehydrogenase
      release, and ATP was quantitated with a luciferin/luciferase assay. Mitochondrial
      membrane potential was stable during 90 min of aerobic perfusion. After 60 and 90
      min of anoxia, mitochondrial membrane potential decreased gradually to 97% +/- 6%
      and 79% +/- 7% of the basal value, respectively. However, mitochondrial membrane
      potential decreased abruptly with reoxygenation after 60 min of anoxia to 45% +/-
      12% of the basal value and did not recover over 30 min of aerobic perifusion.
      Loss of mitochondrial membrane potential could not be attributed to changes of
      cytosolic free calcium, cytosolic pH, nitric oxide generation or activity of
      poly(ADP-ribose) polymerase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517385
TI  - Human genes encoding the voltage-dependent anion channel (VDAC) of the outer
      mitochondrial membrane: mapping and identification of two new isoforms.
AB  - The voltage-dependent anion channel of the mitochondrial outer membrane (VDAC) is
      a small, abundant pore-forming protein found in the outer membranes of all
      eukaryotic mitochondria. The VDAC protein is believed to form the major pathway
      for movement of adenine nucleotides through the outer membrane and to be the
      mitochondrial binding site for hexokinase and glycerol kinase. Previous studies
      have indicated that at least two human VDAC isoforms are expressed. Here, we
      report the mapping of VDAC1 to the X chromosome in the interval Xq13-q21 and
      VDAC2 to chromosome 21 by polymerase chain reaction and restriction analysis of a
      human/rodent somatic cell mapping panel. In the process of mapping these genes,
      we identified and mapped two additional sequences highly homologous to VDAC1.
      VDAC3 maps to chromosome 12 and VDAC4 maps to chromosome 1. The locations of
      VDAC1 and VDAC4 have been confirmed by fluorescence in situ hybridization
      analysis. Future studies will be aimed at defining the specific physiological
      role of each member of this family of channel proteins.

PMID- 7517387
TI  - Dual-color detection of DNA sequence variants by ligase-mediated analysis.
AB  - Genetic screening for sequence variants associated with disease is assuming
      increasing importance in clinical medicine as well as in research. We describe an
      efficient method for such analyses, comprising a combination of practical
      features: (1) Amplified DNA samples are analyzed for their ability to serve as
      templates in standardized allele-specific ligation reactions between
      oligonucleotide probes; (2) Two allele-specific probes, differentially labeled
      with either of two lanthanide labels, compete for ligation to a third
      oligonucleotide (the signal from the two labeled probes can thus be directly
      compared in a sensitive time-resolved fluorescence detection reaction); and (3)
      Large sets of analyses are processed in parallel using a 96-pin capture manifold,
      serving to reduce pipetting steps and the risk of contamination. We present here
      the basis of the technique and its application to the screening for two common
      mutations causing cystic fibrosis and alpha 1-antiytrypsin deficiency.

PMID- 7517388
TI  - Genes for TDP-rhamnose synthesis affect the pattern of lipopolysaccharide
      heterogeneity in Escherichia coli K-12.
AB  - The rough lipopolysaccharide (LPS) of commonly used strains of Escherichia coli K
      12 has two distinctly different band patterns when analyzed by high-resolution
      polyacrylamide gel electrophoresis. The LPS of ancestral strains such as W1485F-
      consists primarily of a single broad gel band. In contrast, the LPS of strains
      derived from strain Y10 such as AB1133 or C600 gives three sharp gel bands.
      Complementation studies using DNA fragments from the rfb gene cluster of Shigella
      dysenteriae 1 indicated that the difference between the two gel patterns is due
      to a mutation in the gene encoding the TDP-rhamnose synthetase, the final enzyme
      involved in TDP-rhamnose biosynthesis. This mutation arose during the
      construction of strain Y10, and not in strain 679-680 as previously thought. The
      requirement for the rfaS gene for synthesis of the broad major band seen in
      W1485F- LPS and the shift in gel migration of a component of this band when an
      rfaQ mutation was introduced indicated that this broad band contained the unique
      form of rough E. coli LPS which has been termed lipooligosaccharide. This finding
      indicates that lipooligosaccharide is likely to contain rhamnose and suggests a
      model in which one of the functions of partial substituents such as rhamnose may
      be to direct core synthesis into different pathways to produce alternative forms
      of LPS.

PMID- 7517389
TI  - Multiple replicons constituting the genome of Pseudomonas cepacia 17616.
AB  - Macrorestriction fragment analysis of DNA from Pseudomonas cepacia 17616, in
      conjunction with Southern hybridization experiments using junction fragments
      containing rare restriction enzyme sites as probes, indicated that this bacterium
      contains three large circular replicons of 3.4, 2.5, and 0.9 megabases (Mb).
      Inclusion of the 170-kb cryptic plasmid present in this strain gave an overall
      estimate of genome size of 7 Mb. Other Southern hybridization experiments
      indicated that the three large replicons contained rRNA genes as well as
      insertion sequence elements identified previously in this strain. The
      distribution of SwaI, PacI, and PmeI sites on the three replicons was determined.
      A derivative of Tn5-751 carrying a SwaI site was used to inactivate and map genes
      on the 2.5- and 3.4-Mb replicons. Mutants were isolated in which the 2.5- and 0.9
      Mb replicons had been reduced in size to 1.8 and 0.65 Mb, respectively. The loss
      of DNA from the 2.5-Mb replicon was associated with lysine auxotrophy, beta
      lactamase deficiency, and failure to utilize ribitol and trehalose as carbon and
      energy sources. DNA fragments corresponding in size to randomly linearized forms
      of the different replicons were detected in unrestricted DNA by pulsed-field gel
      electrophoresis. The results provide a framework for further genetic analysis of
      strain 17616 and for evaluation of the genomic complexities of other P. cepacia
      isolates.

PMID- 7517390
TI  - Genetic analysis of the O-specific lipopolysaccharide biosynthesis region (rfb)
      of Escherichia coli K-12 W3110: identification of genes that confer group 6
      specificity to Shigella flexneri serotypes Y and 4a.
AB  - We recently reported a novel genetic locus located in the sbcB-his region of the
      chromosomal map of Escherichia coli K-12 which directs the expression of group 6
      positive phenotype in Shigella flexneri lipopolysaccharide, presumably due to the
      transfer of O-acetyl groups onto rhamnose residues of the S. flexneri O-specific
      polysaccharide (Z. Yao, H. Liu, and M. A. Valvano, J. Bacteriol. 174:7500-7508,
      1992). In this study, we identified the genetic region encoding group 6
      specificity as part of the rfb gene cluster of E. coli K-12 strain W3110 and
      established the DNA sequence of most of this cluster. The rfbBDACX block of
      genes, located in the upstream region of the rfb cluster, was found to be
      strongly conserved in comparison with the corresponding region in Shigella
      dysenteriae type 1 and Salmonella enterica. Six other genes, four of which were
      shown to be essential for the expression of group 6 reactivity in S. flexneri
      serotypes Y and 4a, were identified downstream of rfbX. One of the remaining two
      genes showed similarities with rfc (O-antigen polymerase) of S. enterica serovar
      typhimurium, whereas the other, located in the downstream end of the cluster next
      to gnd (gluconate-6-phosphate dehydrogenase), had an IS5 insertion. Recently, it
      has been reported that the IS5 insertion mutation (rfb-50) can be complemented,
      resulting in the formation of O16-specific polysaccharide by E. coli K-12 (D. Liu
      and P. R. Reeves, Microbiology 140:49-57, 1994). We present immunochemical
      evidence suggesting that S. flexneri rfb genes also complement the rfb-50
      mutation; in the presence of rfb genes of E. coli K-12, S. flexneri isolates
      express O16-specific polysaccharide which is also acetylated in its rhamnose
      residues, thereby eliciting group 6 specificity.

PMID- 7517392
TI  - Genetic insertion and exposure of a reporter epitope in the ferrichrome-iron
      receptor of Escherichia coli K-12.
AB  - The ferrichrome-iron receptor of Escherichia coli K-12 is FhuA (M(r), 78,992),
      the first component of an energy-dependent, high-affinity iron uptake pathway.
      FhuA is also the cognate receptor for bacteriophages T5, T1, phi 80, and UC-1,
      for colicin M and microcin 25, and for albomycin. To probe the topological
      organization of FhuA which enables recognition of these different ligands, we
      generated a library of 16 insertion mutations within the fhuA gene. Each
      insertion spliced a 13-amino-acid antigenic determinant (the C3 epitope of
      poliovirus) at a different position within FhuA. Immunoblotting of outer
      membranes with anti-FhuA and anti-C3 antibodies indicated that 15 of 16 FhuA.C3
      proteins were present in the outer membrane in amounts similar to that observed
      for plasmid-encoded wild-type FhuA. One chimeric protein with the C3 epitope
      inserted after amino acid 440 of FhuA was present in the outer membrane in
      greatly reduced amounts. Strains overexpressing FhuA.C3 proteins were subjected
      to flow cytometric analysis using anti-FhuA monoclonal antibodies. Such analysis
      showed that (i) the chimeric proteins were properly localized and (ii) the wild
      type FhuA protein structure had not been grossly altered by insertion of the C3
      epitope. Twelve of sixteen strains expressing FhuA.C3 proteins were proficient in
      ferrichrome transport and remained sensitive to FhuA-specific phages. Three
      FhuA.C3 proteins, with insertions after amino acid 321, 405, or 417 of FhuA, were
      detected at the cell surface by flow cytometry using anti-C3 antibodies. These
      three chimeric proteins were all biologically active. We conclude that amino
      acids 321, 405, and 417 are surface accessible in wild-type FhuA.

PMID- 7517391
TI  - Structure of the O antigen of Escherichia coli K-12 and the sequence of its rfb
      gene cluster.
AB  - Escherichia coli K-12 has long been known not to produce an O antigen. We
      recently identified two independent mutations in different lineages of K-12 which
      had led to loss of O antigen synthesis (D. Liu and P. R. Reeves, Microbiology
      140:49-57, 1994) and constructed a strain with all rfb (O antigen) genes intact
      which synthesized a variant of O antigen O16, giving cross-reaction with anti-O17
      antibody. We determined the structure of this O antigen to be -->2)-beta-D-Galf
      (1-->6)-alpha-D-Glcp- (1-->3)-alpha-L-Rhap-(1-->3)-alpha-D-GlcpNAc-(1-->, with an
      O-acetyl group on C-2 of the rhamnose and a side chain alpha-D-Glcp on C-6 of
      GlcNAc. O antigen synthesis is rfe dependent, and D-GlcpNAc is the first sugar of
      the biological repeat unit. We sequenced the rfb (O antigen) gene cluster and
      found 11 open reading frames. Four rhamnose pathway genes are identified by
      similarity to those of other strains, the rhamnose transferase gene is identified
      by assay of its product, and the identities of other genes are predicted with
      various degrees of confidence. We interpret earlier observations on interaction
      between the rfb region of Escherichia coli K-12 and those of E. coli O4 and E.
      coli Flexneri. All K-12 rfb genes were of low G+C content for E. coli. The
      rhamnose pathway genes were similar in sequence to those of (Shigella)
      Dysenteriae 1 and Flexneri, but the other genes showed distant or no similarity.
      We suggest that the K-12 gene cluster is a member of a family of rfb gene
      clusters, including those of Dysenteriae 1 and Flexneri, which evolved outside E.
      coli and was acquired by lateral gene transfer.

PMID- 7517393
TI  - Involvement of the galactosyl-1-phosphate transferase encoded by the Salmonella
      enterica rfbP gene in O-antigen subunit processing.
AB  - rfbT of Salmonella enterica LT2 was previously thought, together with rfaL, to be
      involved in the ligation of polymerized O antigen to core-lipid A, and three
      mutants were known. We report the mapping of the mutations to rfbP, the
      galactosyl-1-phosphate transferase gene, which is now shown to encode a
      bifunctional protein. The mutations which have the former rfbT phenotype are
      referred to as rfbP(T). We also show that rfbP(T) mutants are not blocked in the
      ligation step as previously believed but in an earlier step, possibly in flipping
      the O-antigen subunit on undecaprenyl pyrophosphate from the cytoplasmic to
      periplasmic face of the cytoplasmic membrane.

PMID- 7517394
TI  - Insertional activation of cepA leads to high-level beta-lactamase expression in
      Bacteroides fragilis clinical isolates.
AB  - Bacteroides fragilis is an important opportunistic pathogen of humans and is
      resistant to many drugs commonly used to treat anaerobic infections, including
      beta-lactams. A strain set comprised of B. fragilis isolates producing either low
      or high levels of the endogenous cephalosporinase activity, CepA, has been
      described previously (M. B. Rogers, A. C. Parker, and C. J. Smith, Antimicrob.
      Agents Chemother. 37:2391-2400, 1993). Clones containing cepA genes from each of
      seven representative strains were isolated, and the DNA sequences were
      determined. Nucleotide sequence comparisons revealed that there were few
      differences between the cepA coding sequences of the low- and high-activity
      strains. The cepA coding sequences were cloned into an expression vector, pFD340,
      and analyzed in a B. fragilis 638 cepA mutant. The results of beta-lactamase
      assays and ampicillin MICs showed that there was no significant difference in the
      enzymatic activity of structural genes from the high- or low-activity strains.
      Comparison of sequences upstream of the cepA coding region revealed that 50 bp
      prior to the translation start codon, the sequence for high-activity strains
      change dramatically. This region of the high-activity strains shared extensive
      homology with IS21, suggesting that an insertion was responsible for the
      increased expression of cepA in these isolates. Northern (RNA) blot analysis of
      total RNA by using cepA-specific DNA probes supported the idea that differential
      cepA expression in low- and high-activity strains was controlled at the level of
      transcription. However, the insertion did not alter the cepA transcription start
      site, which occurred 27 bp upstream of the ATG translation start codon in both
      expression classes. Possible mechanisms of cepA activation are discussed.

PMID- 7517395
TI  - Thiobacillus ferrooxidans tyrosyl-tRNA synthetase functions in vivo in
      Escherichia coli.
AB  - The tyrosyl-tRNA synthetase gene (tyrZ) from Thiobacillus ferrooxidans, an
      acidophilic, autotrophic, gram-negative bacterium that participates in
      bioleaching of minerals, was cloned and sequenced. The encoded polypeptide
      (TyrRZ) is 407 amino acids in length (molecular mass; 38 kDa). The predicted
      protein sequence has an extensive overall identity (44%) to the sequence of the
      protein encoded by the Bacillus subtilus tyrZ gene, one of the two genes encoding
      tyrosyl-tRNA synthetases in this microorganism. Alignment with Escherichia coli
      TyrRS revealed limited overall identity (24%), except in the regions of the
      signature sequence for class I aminoacyl-tRNA synthetases. Complementation of an
      E. coli strain with a thermosensitive mutation in TyrRS showed that the protein
      encoded by the T. ferrooxidans tyrZ gene is functional and recognizes the E. coli
      tRNA(Tyr) as a substrate. TyrZ is a single-copy gene as revealed by Southern blot
      analysis. The gene was localized upstream from the putative promoters of the
      rrnT2 ribosomal RNA operon. Although no rho-independent transcription terminator
      was found between the two genes, a 1.3-kb RNA hybridized to a DNA probe derived
      from the tyrZ gene. The functional relationship between these two transcription
      units is discussed.

PMID- 7517397
TI  - Physical association between Src homology 3 elements and the protein product of
      the c-cbl proto-oncogene.
AB  - To investigate the nature of proteins recognized by Src homology 3 (SH3) domains,
      a cDNA expression library was prepared from macrophages and screened with a probe
      representing the three SH3 domains of p47nck. Two clones were isolated, and one,
      designated SAKAP I (for Src A box Nck-associated protein I), contained the
      carboxyl-terminal half of the cbl proto-oncogene product. Studies in vitro
      demonstrated reactivity between SAKAP I and SH3 domains derived from a variety of
      molecules. Wide variations in this assay suggested a high degree of specificity
      inherent in SAKAP I binding. Moreover, it was possible to demonstrate an in vivo
      association between p47nck and p120c-cbl in HL60 cells. These findings suggest
      that proteins containing SH3 elements regulate Cbl function.

PMID- 7517396
TI  - Cloning and analysis of a locus (mcr) involved in mitomycin C resistance in
      Streptomyces lavendulae.
AB  - Two genes (mcrA and mcrB) from Streptomyces lavendulae that together confer
      resistance to mitomycin C were identified. This DNA appears to comprise a
      polycistronic operon with a drug-inducible leaderless mRNA. The deduced amino
      acid sequence of mcrA shows similarity to sequences of a special class of
      bacterial, plant, and animal oxygen oxidoreductases.

PMID- 7517398
TI  - Bactericidal/permeability-increasing protein and lipopolysaccharide (LPS)-binding
      protein. LPS binding properties and effects on LPS-mediated cell activation.
AB  - We have previously shown that human bactericidal/permeability-increasing protein
      (BPI) is able to inhibit serum-dependent lipopolysaccharide (LPS)-mediated
      activation of human monocytes and neutrophils in vitro, and to counteract the
      lethal effects of LPS challenge in vivo. Lipopolysaccharide-binding protein (LBP)
      is a serum protein which participates in LPS-mediated activation of cells
      (Tobias, P. S., Mathison, J., Mintz, D., Lee, J. D., Kravchenko, V., Kato, K.,
      Pugin, J., and Ulevitch, R. J. (1992) Am. J. Respir. Cell. Mol. Biol. 7, 239
      245). We have proposed that BPI functions in a negative feedback loop which
      opposes this activation (Marra, M. N., Wilde, C. G., Collins, M. S., Snable, J.
      L., Thornton, M. B., and Scott, R. W. (1992) J. Immunol. 148, 532-537). We have
      now cloned and expressed recombinant forms of human BPI and LBP. Here we
      demonstrate that purified recombinant human LBP can replace the serum requirement
      for both LPS binding to human monocytes and LPS-mediated secretion of tumor
      necrosis factor alpha from these cells. These activities of LBP are inhibited by
      a neutralizing anti-CD14 monoclonal antibody. We further demonstrate that
      purified recombinant human BPI can inhibit LBP-mediated LPS binding to cells and
      their subsequent activation. Comparison of the LPS binding properties of BPI and
      LBP in enzyme-linked immunosorbent type assays and in the Limulus amebocyte
      lysate assay suggest that BPI has a stronger affinity for LPS than does LBP.
      Direct competition between BPI and LBP for LPS may explain the inhibition by BPI
      of the proinflammatory effects of LBP in the presence of LPS.

PMID- 7517399
TI  - Rapid filtration studies of the effect of cytosolic Ca2+ on inositol 1,4,5
      trisphosphate-induced 45Ca2+ release from cerebellar microsomes.
AB  - Using microsomal membrane vesicles derived from sheep cerebellum, we measured the
      rate of inositol 1,4,5-trisphosphate (InsP3)-dependent 45Ca2+ efflux from
      45Ca(2+)-loaded compartments during rapid perfusion with a medium containing
      InsP3 and various concentrations of free 40Ca2+ on the cytosolic side (pH 7.1, 5
      mM Mg2+, in the absence of ATP at 20 degrees C). At 0.15 microM InsP3 and pCa
      6.5, half-45Ca2+ release was attained within less than 200 ms. At low Ca2+
      concentrations, the initial rate of 45Ca2+ release depended smoothly on InsP3
      concentration, and InsP3 activated release with moderate positive cooperativity.
      Preliminary experiments performed at various free 40Ca2+ concentrations were
      consistent with a bell-shaped 40Ca2+ dependence of 45Ca2+ release. In the range
      of micromolar or higher free 40Ca2+ concentrations, the apparent inhibition of
      45Ca2+ release was dependent on InsP3 concentration, and 45Ca2+ release for
      intermediate InsP3 concentrations was transient; under selected conditions, a
      second perfusion period, identical to the first one but separated from it by a
      short recovery period, was found to allow renewed 45Ca2+ efflux. At high Ca2+
      concentration, fast reversible Ca(2+)-dependent desensitization of the channel,
      and not heterogeneity, was therefore responsible for the termination of InsP3
      triggered 45Ca2+ efflux at submaximal concentrations of InsP3. At lower Ca2+
      concentrations, a large fraction of the apparent activating effect of
      submicromolar 40Ca2+ concentrations on 45Ca2+ efflux that we had observed in the
      preliminary experiments proved to be the artifactual consequence of an inhibitory
      effect exerted by metal-free Ca2+ chelators on InsP3-dependent efflux at
      nanomolar 40Ca2+ concentrations. 1,2-Bis(2-aminophenoxy)ethane-N,N,N'-N'
      tetraacetic acid, EGTA, and fluo-3 were all effective inhibitors. When this
      inhibition was taken into account, a rise in free 40Ca2+ concentration from 30 to
      300 nM only weakly enhanced 45Ca2+ fluxes in the presence of a low concentration
      of InsP3. As a result, submicromolar free 40Ca2+ appears to be only a poor
      activator of InsP3-induced Ca2+ release under these experimental conditions.

PMID- 7517402
TI  - Mechanism of cigarette smoke condensate induced adhesion of human monocytes to
      cultured endothelial cells.
AB  - Cigarette smoking is ranked among the leading risk factors in the etiology of
      atherosclerotic vascular disease. The mechanisms, however, that link cigarette
      smoking to increased incidence of atherosclerosis are not understood. The
      adherence of circulating monocytes to the endothelium, migration into the
      subendothelium, and subsequent formation of foam cells are principal initial
      events in the development of atherosclerosis. We therefore determined whether
      cigarette smoke caused increased adherence of monocytes to endothelial cells and
      the cellular mechanism of this increased adherence. Cigarette smoke condensate
      (CSC), the particulate fraction of cigarette smoke derived from 2R1 standard
      research cigarettes, at a concentration of 25-30 micrograms/ml (average yield of
      CSC is 26.1 mg/cigarette), augmented (70-90%) basal adherence of human peripheral
      blood monocytes to a cultured monolayer of endothelial cells derived from bovine
      aorta (BAEC) and human umbilical vein (HUVEC). There was a concomitant increase
      in the expression of CD11b ligand on the surface of monocytes as determined by
      flow cytometry, utilizing FITC conjugated Mab MO-1 (CD11b). However, nicotine (1
      15 micrograms/ml) and cadmium sulfate (10 micrograms/ml), constituents of CSC,
      individually or in combination had no effect either on CD11b expression or
      adherence of monocytes to endothelial cells. Treatment of HUVEC with CSC for 60
      min also resulted in an increased expression of ICAM-1 and ELAM-1 as determined
      by mean fluorescence intensity of ICAM-1 and ELAM-1 labeled cells in flow
      cytometric analysis. The CSC induced expression of CD11b in monocytes was optimal
      at 25-30 min and was inhibited by protein kinase C inhibitors, staurosporine and
      H-7, and also by baicalein, a lipoxygenase inhibitor. Similarly, CSC induced ICAM
      1 and ELAM-1 expression in HUVEC was inhibited by protein kinase C inhibitors.
      CSC stimulated the adherence of human monocytes but not the monocytic cell lines
      HL-60, U937, and THP-1 to endothelial cells. The CSC stimulated adherence of
      human monocytes was inhibited (80%) by MAb to CD11b and 50% by Mab to ICAM-1 and
      ELAM-1. These results suggest that cigarette smoke particulate constituents
      activate protein kinase C, leading to increased surface expression of adhesive
      ligand CD11b on peripheral blood monocytes and counter receptor(s) ICAM-1 and
      ELAM-1 in endothelial cells. The expression of ligand and counter receptor leads
      to potentiated adherence of monocytes to endothelial cells, an initial event in
      the pathogenesis of cigarette smoke induced inflammatory response in the vessel
      wall.

PMID- 7517401
TI  - Raf-1 interacts with Fyn and Src in a non-phosphotyrosine-dependent manner.
AB  - To identify novel proteins capable of associating with the Raf-1 serine/threonine
      kinase, we investigated whether Raf-1 could interact with the Src homology 2
      (SH2) domains of various signal-transducing molecules. In this report, we
      demonstrate that Raf-1 associated with the SH2 domain of Fyn (a member of the Src
      tyrosine kinase family) but not with the SH2 domains of phospholipase C-gamma 1,
      the p85 alpha subunit of phosphatidylinositol 3-kinase, and SH2-containing
      protein tyrosine phosphatase 2. Unlike most SH2 domain interactions that require
      tyrosine-phosphorylated residues, the Raf-1/Fyn SH2 domain association was
      dependent on the serine phosphorylation of Raf-1. Our results also demonstrate
      that Raf-1 interacted with the SH2 domain of Src and that this interaction was
      destabilized by mutation of Arg175 found within the conserved SH2 domain FLVRES
      sequence. In addition, we show that inclusion of additional Src sequences
      containing the SH3 domain increased the association of Raf-1 with the Src SH2
      domain. Finally, using the baculovirus/Sf9 cell system, we show that coexpression
      of Raf-1 with full-length Fyn/Src resulted in the coimmunoprecipitation of Raf-1
      with Fyn/Src, the tyrosine phosphorylation of Raf-1, and the stimulation of Raf-1
      kinase activity. These results suggest that Raf-1 may form a functional complex
      with Fyn/Src mediated in part by SH2 domains and the serine phosphorylation of
      Raf-1.

PMID- 7517400
TI  - Identification and characterization of a promiscuous chemokine-binding protein in
      a human erythroleukemic cell line.
AB  - The erythrocyte chemokine receptor is a cell surface protein that binds a wide
      array of chemokines including interleukin-8 (IL-8), melanoma growth stimulating
      activity (MGSA), monocyte chemotactic protein-1 (MCP-1), and RANTES (Regulated on
      Activation, Normal T Expressed and Secreted). This protein has also been
      identified as the Duffy blood group antigen, a cell surface receptor for the
      malarial parasite Plasmodium vivax. In the present study, we have identified a
      chemokine receptor-like binding protein in a human erythroleukemic cell line
      (HEL), which, based on its molecular properties, may be related to the
      erythrocyte chemokine receptor. Saturation binding studies with 125I-IL-8
      revealed a single class of IL-8 binding sites in HEL cells with a KD of 7.4 +/-
      1.9 nM and a receptor density of 12,818 +/- 965 binding sites/cell. In
      competition studies unlabeled IL-8 MGSA, MCP-1, and RANTES were fully able to
      inhibit the binding of 125I-IL-8 to HEL cells. Chemical cross-linking with
      radiolabeled IL-8 resulted in a cross-linked species of 60 kDa in membranes from
      HEL cells. The labeling was specific since it was inhibited by pre-incubation
      with 1 microM unlabeled IL-8 or MGSA. A monoclonal antibody (Fy6) to the human
      erythrocyte Duffy blood group antigen/chemokine receptor blocked the binding of
      IL-8 and other chemokines to the HEL cell chemokine receptor-like binding
      protein. Cell membranes from HEL cells and from erythrocyte ghosts were subjected
      to SDS-PAGE and analyzed by Western blotting with anti-Fy6. The antibody bound to
      a molecule with a molecular mass of 50 kDa in HEL cell membranes and 40 kDa in
      erythrocyte ghosts. Northern blot analysis of mRNA revealed that the HEL
      chemokine-binding protein hybridized to a cDNA probe to the Duffy
      antigen/chemokine receptor.

PMID- 7517404
TI  - Laminin SIKVAV peptide-induced angiogenesis in vivo is potentiated by
      neutrophils.
AB  - Angiogenesis has been investigated in vivo using subcutaneously injected
      reconstituted basement membrane (Matrigel) supplemented with angiogenic factors.
      Previously we found that the laminin-derived synthetic peptide containing SIKVAV
      (ser-ile-lys-val-ala-val) promoted angiogenesis in vivo. In parallel studies, it
      was observed that new vessel formation in response to this peptide occurred
      several days after basic fibroblast growth factor-induced angiogenesis. Since
      this delay suggested that SIKVAV-induced angiogenesis may be secondary to other
      events, we investigated here earlier time points to determine if both indirect
      and direct mechanisms of angiogenesis are involved. We found that neutrophils are
      continuously recruited to the SIKVAV-containing plugs between 4 hours to 3 days
      following the initial injection. By day 7, columns of endothelial cells begin to
      migrate into the plug and form small blood vessels. In contrast, neutropenic mice
      had a 62% reduction in SIKVAV-induced angiogenesis when compared to control mice.
      Freshly isolated neutrophils also degraded laminin, the major component of the
      basement membrane Matrigel. These cells also produced factors in response to
      SIKVAV peptide which induced proliferation of human umbilical vein endothelial
      cells relative to a control peptide. In vitro experiments utilizing human
      neutrophils demonstrated that these cells migrate to the SIKVAV peptide and
      possess a specific cell surface SIKVAV binding protein of approximately 56 kD.
      These data suggest that neutrophils are induced to migrate to the Matrigel plugs,
      at least in part, by SIKVAV peptide, where they may release their own angiogenic
      factors and degrade the matrix, thus physically facilitating cell migration and
      liberating additional angiogenic matrix fragments and/or cytokines.

PMID- 7517403
TI  - Complex pattern of insulin-like growth factor binding protein expression in
      primary rat osteoblast enriched cultures: regulation by prostaglandin E2, growth
      hormone, and the insulin-like growth factors.
AB  - Primary osteoblast-enriched (Ob) cultures from fetal rat bone synthesize insulin
      like growth factor (IGF) I and IGF-II, which each enhance Ob function. While a
      number of agents modulate IGF-I production, IGF-II is constitutively expressed in
      this culture model. Independent of their expression, however, the activity of the
      IGFs can be modified by a small group of proteins termed IGF binding proteins
      (IGFBPs), but little is known about the regulation of individual IGFBPs that are
      synthesized by Ob cells. Northern blot analysis revealed that serum-deprived
      primary rat Ob cells express transcripts encoding IGFBP-2, IGFBP-3, IGFBP-4,
      IGFBP-5, and IGFBP-6, but undetectable levels of IGFBP-1 transcripts. Western
      ligand blots of Ob culture medium probed with 125I-IGF-I or 125I-IGF-II showed
      predominant IGFBPs migrating at 30/32 kDa, with minor bands at 24 and 38-47 kDa.
      Western antibody analysis identified IGFBP-2 and IGFBP-5 within the 30/32 kDa
      complex, while gel mobility shift on SDS-PAGE following deglycosylation
      determined that IGFBP-3 comprised the 38-47 kDa complex. By Northern analysis, 6
      h treatment with prostaglandin E2 (PGE2), growth hormone (hGH), IGF-I, or IGF-II
      revealed a complex pattern of regulatory effects on steady-state IGFBP transcript
      expression. PGE2 increased the transcript levels of IGFBP-3, IGFBP-4, and IGFBP
      5, (approximately 22-, approximately 2- and approximately 4-fold respectively),
      but had no effect on IGFBP-2 or IGFBP-6 transcripts. hGH enhanced IGFBP-3 and
      IGFBP-5 transcripts (each approximately twofold). IGF-I and IGF-II had no effect
      on IGFBP-2 steady-state transcript levels but enhanced the level of IGFBP-5
      transcripts (approximately fourfold). By Western ligand blot analysis, 24 h
      treatment with PGE2 elevated the 24 and 38-47 kDa IGFBPs and to a lesser extent
      the 30/32 kDa complex, hGH elevated the 38-47 kDa IGFBPs, and IGF-I and IGF-II
      each increased the 30/32 kDa IGFBP complex. Therefore, a comparison of results
      obtained from Northern, Western ligand, and Western antibody studies indicates
      that multiple IGFBPs are expressed by primary rat Ob cultures. While IGFBP-2 and
      IGFBP-6 synthesis in Ob cultures is relatively unaffected by short-term treatment
      with PGE2, hGH, or the IGFs, these agents modify IGFBP-3, IGFBP-4, and IGFBP-5
      expression with individual patterns of effects. In addition, some changes in
      IGFBP polypeptide levels that are independent of alterations in transcript
      expression may result from the formation of complexes between IGFs and certain
      IGFBPs, which could serve to store IGFs for future utilization in the formation
      phase of bone remodeling.

PMID- 7517405
TI  - Inhibition of angiogenesis by tissue inhibitor of metalloproteinase.
AB  - Matrix proteases play a critical role in cell invasion and migration, including
      the process of angiogenesis. The ability of specific factors to induce angiogenic
      responses correlates with their stimulation of matrix protease synthesis and
      release. Using an in vivo angiogenesis assay, the endothelial cell response to
      known angiogenic factors, basic fibroblast growth factor (bFGF) and adipocyte
      conditioned medium, was blocked by an inhibitor of matrix metalloproteinase
      activity, TIMP-1. The TIMP effect was mediated, at least in part, through the
      inhibition of endothelial cell migration, as determined by the ability of TIMP to
      block chemotaxis in a Boyden chamber assay. These results indicate that the
      inhibition of migration is a direct effect on the endothelial cells and does not
      require accessory cells. An additional observation was that the RNA levels for
      TIMP were significantly reduced in differentiated adipocytes, compared to
      undifferentiated F442A controls. Therefore, the acquisition of an angiogenic
      phenotype may involve not only the induction of positive factors, but also the
      suppression of angiogenesis inhibitors.

PMID- 7517406
TI  - Senescence and cell density of human diploid fibroblasts influence metabolism of
      insulin-like growth factor binding proteins.
AB  - In order to analyze changes in metabolism of insulin-like growth factor binding
      proteins (IGFBPs) related to cell senescence and cell density, we compared human
      diploid fibroblasts (HDF) in the proliferatively vigorous first half (young
      cells) and senescent HDF in the last 10% (old cells) of the replicative lifespan
      after seeding cells over an eightfold range and proliferation to high density.
      Increasing the seeding cell density of both young and old HDF led to elevated
      rates of IGFBP-3 secretion, an increasing ratio of the 42/38 kDa species of IGFBP
      3, and degradation of all species of IGFBPs derived from both the fetal bovine
      serum component of the culture medium and from HDF. At a given seeding density
      old HDF produced more IGFBP-3 and degraded more IGFBPs than young HDF. IGFBP-4
      was degraded by a protease that appeared to be different from the protease(s)
      involved in degradation of the other IGFBPs. Young HDF at all seeding densities
      contained a cell-associated 29 kDa IGFBP, whereas this protein could not be
      detected in old cells. Thus, although certain changes in IGFBP metabolism are
      similar in young HDF seeded at high densities and in old HDF, young and old
      phenotypes can be distinguished by characteristic qualitative and quantitative
      changes in IGFBPs derived from fetal bovine serum and from HDF.

PMID- 7517407
TI  - Age and development-related changes in osteopontin and nitric oxide synthase mRNA
      levels in human kidney proximal tubule epithelial cells: contrasting responses to
      hypoxia and reoxygenation.
AB  - Osteopontin (OPN) encodes a secreted glycosylated phosphoprotein containing a
      GRGDS motif that can mediate cell attachment through the alpha v beta 3 integrin,
      and has recently been shown to down-regulate nitric oxide synthase (NOS)
      expression. We report here that primary cultures of renal proximal tubule
      epithelial (PTE) cells prepared from human kidneys of different developmental
      stages and ages show a positive correlation between developmental age and the
      expression, at the mRNA level, of both OPN and constitutive NOS. However, OPN and
      NOS responded in different manners, as assessed by mRNA measurements, to hypoxia
      reoxygenation injury. The OPN mRNA level, assessed by Northern blotting,
      increased slightly during 60 min of hypoxia and more substantially during
      subsequent reoxygenation of primary PTE cells derived from the kidneys of young
      but not of aged donors. The abundance of NOS mRNA, measured using a cDNA probe to
      the constitutive form of the enzyme, was enhanced during hypoxia in kidneys
      derived from humans of all ages, and then decreased during reoxygenation-
      possibly as the result of increased OPN expression. PTE cells from aged kidneys
      are more susceptible to cell death under hypoxic conditions that PTE cells from
      young kidneys. An investigation of the effect of an oxidant on OPN and NOS mRNA
      levels revealed that within 30 min of exposure to H2O2, NOS mRNA levels decreased
      simultaneously with an increase in OPN mRNA levels. Nitric oxide (NO), the
      product of NOS, is at low levels an important signal transduction molecule
      participating in the regulation of vascular tone and renal reabsorption; at high
      levels it is cytotoxic. We suggest that the diminished ability of cells from old
      kidneys to down-regulate NO production and to increase OPN expression after
      hypoxia-reoxygenation may contribute to their increased susceptibility to oxidant
      injury.

PMID- 7517410
TI  - A study of SMI 32-stained pyramidal cells, parvalbumin-immunoreactive chandelier
      cells, and presumptive thalamocortical axons in the human temporal neocortex.
AB  - Immunocytochemical studies in the primate neocortex have shown that particular
      populations of pyramidal cells can be identified by antibody SMI 32 that
      recognizes a nonphosphorylated epitope of neurofilament protein, while chandelier
      cells (a powerful type of cortical inhibitory interneuron) and presumptive
      thalamocortical axons can be identified by antibodies directed against the
      calcium-binding protein parvalbumin (PV). We used these antibodies in correlative
      light and electron microscopic immunocytochemical studies to analyze certain
      aspects of the synaptic circuitry of human temporal neocortex. In sections cut in
      the tangential plane, many PV-immunoreactive chandelier cell axon terminals and
      apical dendrites of SMI 32-stained pyramidal cells were distributed in small
      clusters. Combination of immunocytochemistry for PV and SMI 32 revealed four
      subpopulations of pyramidal cells with regard to the immunocytochemical staining
      by SMI 32 and the innervation of their axon initial segments by PV-positive or 
      negative chandelier cell axon terminals, but there were differences in the
      concentration and proportion of these subpopulations by layers. Furthermore, we
      present electron microscopic evidence suggesting that the characteristic layer
      III dense band of PV-immunoreactive puncta is made up mainly of presumptive
      thalamocortical axon terminals. Besides, coincidence was found between the dense
      PV-immunoreactive band and the dendritic plexus formed by the SMI 32-stained
      pyramidal cells in the lower half of layer III, which leads us to think that they
      are probably a major target of PV-immunoreactive thalamic terminations.

PMID- 7517409
TI  - Effect of zatosetron on ipecac-induced emesis in dogs and healthy men.
AB  - Serotonin receptor (5-HT3) antagonists provide effective antiemetic therapy in
      cancer patients receiving emetogenic chemotherapy, such as cisplatin. Animal
      studies have shown that 5-HT3 receptor antagonists also have antiemetic activity
      in ipecac-induced emesis. The authors investigated the antiemetic activity of
      zatosetron maleate, a 5-HT3 receptor antagonist, on ipecac-induced emesis in dogs
      and healthy men. They also evaluated the effect of ipecac administration on
      serotonin release and metabolism by measuring urinary 5-hydroxyindoleacetic acid
      (5-HIAA) excretion in healthy men. In separate randomized, placebo-controlled
      trials, 20 dogs received zatosetron intravenously and eight healthy men received
      zatosetron (50 mg) orally, followed by ipecac syrup. In both trials, emetic
      response to ipecac was recorded, including the number and time of vomits and
      retches. Zatosetron treatment inhibited and delayed ipecac-induced emesis in both
      groups. In dogs, zatosetron inhibited ipecac-induced emesis in a dose-dependent
      manner with a 100-micrograms/kg dose producing complete inhibition. In men,
      zatosetron administration resulted in fewer emetic episodes after ipecac than had
      occurred with placebo administration (P = .03); vomiting was completely inhibited
      by zatosetron. In men, ipecac administration did not affect the urinary 5
      HIAA/creatinine ratio (mg/g) or 5-HIAA excretion rate (microgram/hour). Our study
      demonstrates that zatosetron has similar efficacy on ipecac-induced emesis in
      healthy men, as has been shown previously with other 5-HT3 receptor antagonists
      in chemotherapy-induced emesis in cancer patients. We did not observe the
      increase of urinary 5-HIAA in our study with ipecac-induced emesis, however, as
      has been described previously in cisplatin-induced emesis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7517408
TI  - Recovery of nuclear matrix ultrastructure of interphase CHO cells after heat
      shock.
AB  - Heat shock induces changes in G1 CHO cell nuclear matrix (NM) ultrastructure that
      may be related to heat-induced nuclear protein accumulation (Wachsberger and
      Coss, 1993, J. Cell. Physiol., 155:615-634). The present study quantitates
      recovery of alterations in NM fine structure in CHO cells heated in G1 and
      compares structural recovery with recovery of bulk RNA synthesis and surviving
      fraction (SF). Morphology of NM preparations was quantified 30 min and 20 hr
      following heat shock by 1) measurement of the number of fiber anastomosing points
      per unit area per NM, and 2) measurement of the length of fibers between points
      of anastomoses within individual NMs. Architectural recovery was nearly complete
      within 20 hr in cells heated at 43 degrees C or 45 degrees C with SFs of 0.27 or
      greater. No recovery of architecture was observed in heated cells with SFs of
      approximately 0.01 or less. The residual damage to NMs was associated with RNA
      containing fiber networks as determined by means of RNase gold labeling. Recovery
      from inhibition of RNA synthesis following heat shock was related to recovery of
      NM architecture. It is suggested that 1) repair of NM architecture does not
      require full recovery of bulk RNA synthesis, and 2) partial or complete
      irreversible collapse of the NM may be responsible, in part, for heat-induced,
      interphase cell death.

PMID- 7517412
TI  - An observational study of the role of pain control and food adaptation of elderly
      patients with terminal cancer.
AB  - Anorexia and a distaste for food are common in patients with terminal cancer and
      often lead to the use of invasive therapeutic measures. In our prospective study
      involving 116 elderly patients with terminal cancer, we found that this
      nutritional behavior could be modified by making certain changes in the
      treatment. The most important of these are control of pain and distressing
      symptoms and nutritional adaptation to the condition and tastes of the patients.
      Ninety-two percent of the subjects could eat until the day they died. The eating
      pattern of these patients was found to be identical to that observed in elderly
      patients without cancer. Only 15 patients who had cancer (13%) refused food
      containing meat.

PMID- 7517411
TI  - Merkel cells and prurigo nodularis.
AB  - BACKGROUND: Increased numbers of dermal nerves have been demonstrated in prurigo
      nodularis and have been theoretically linked to the intense pruritus. We
      hypothesized that the neuronal proliferation in prurigo nodularis might be
      associated with an increased density of Merkel cells because they are also a
      component of the neurocutaneous system. METHODS: We examined skin biopsy
      specimens from 20 cases of prurigo nodularis for Merkel cells with the use of a
      standard immunohistochemical assay (avidin-biotin-peroxidase complex system) with
      an antibody to cytokeratin 8 (CAM 5.2). Six cases of lichen simplex chronicus
      were examined as controls. RESULTS: Merkel cells were present in the
      interfollicular area of the basal cell layer in 15 (75%) of 20 prurigo nodularis
      cases and in one (17%) of six cases of lichen simplex chronicus. CONCLUSION:
      Merkel cells are increased in number in prurigo nodularis and may be a component
      of the neurocutaneous abnormality associated with this disorder.

PMID- 7517413
TI  - 5-HT-related, anxiety- and/or aggression-driven depression.
AB  - Mood lowering is considered to be the prime factor in the diagnosis of
      depression. However, it has been proposed that in a subset of cases of
      depression, the primary symptoms are anxiety and/or aggression. It has also been
      shown that these symptoms coincide with disturbance of 5-hydroxytryptamine (5
      HT), which is frequently seen in depressed patients and has been suggested to be
      a vulnerability factor in the onset of depressive phases. If the concept of this
      proposed subset of depression--termed "5-HT-related, anxiety-and/or aggression
      driven depression"--is accepted, this will lead to a review of the mode of
      diagnosis of depression and a reorientation of research into antidepressant
      drugs.

PMID- 7517414
TI  - Studies of the distribution and functional roles of transitory amoeboid
      microglial cells in developing rat brain using exogenous horseradish peroxidase
      as a marker.
AB  - When HRP was injected intraperitoneally (i. p.), labelled amoeboid microglial
      cells (AMC) were consistently localized in the subcortical white matter and
      circumventricular zones in early postnatal (1 and 7 days old) but absent in late
      postnatal (14-day-old) rats. The ingested HRP disappeared from the labelled cells
      5 days after IP injection. Subcutaneous injection of HRP had also resulted in the
      labelling of amoeboid microglial cells in the corpus callosum of early postnatal
      rats. When the injected HRP was followed ultrastructurally over a time course
      sequence in intravenously (i. v.) injected rats, it was first detected in the
      invaginations on the luminal side of endothelium and in the endothelial cytoplasm
      30 min after injection. HRP was present both in the endothelium and amoeboid
      microglial cells 3 hours later. With time, the tracer was progressively
      accumulated in the cytoplasm of AMC and it was sequestered in the vacuoles and
      lysosomes. It is concluded from this study that when injected i. p., i. v. or
      subcutaneously in the early postnatal rats, HRP is circulated to the blood
      vessels in the subcortical white matter and circumventricular zones where it
      gains access into the nervous tissues by transendothelial transport. The
      extravasated tracer is then phagocytosed by the residential AMC and subsequently
      degraded. The absence of labelling of AMC is attributed to the maturation of BBB
      which impedes the entry of exogenous tracer by the 14th postnatal day.

PMID- 7517415
TI  - Central projections of the octaval nerve in larval lamprey: an HRP study.
AB  - HRP tracing techniques and silver staining methods were used to investigate the
      central projections of the octaval nerve of the larval sea lamprey (Petromyzon
      marinus). We compare our findings with those reported for the adult and for other
      anamniotes. The general pattern of afferent projections (to the ventral
      octavolateral area of the medulla oblongata and to the cerebellar plate) is
      similar to that in the adult, although we did not observe projections to the
      trigeminal, reticular or contralateral medullary areas. We describe the pattern
      of connections of the octaval afferents with the different octaval nuclei (i.e.
      subdivisions of the ventral octavolateral area), and report the presence of a
      small number of efferent vestibular neurons.

PMID- 7517417
TI  - Afferent and efferent connections of the dorsal column nuclear complex and
      adjacent regions in the turtle.
AB  - Anterograde and retrograde tracer substances were injected into the dorsal
      spinomedullary region (DSM), which in the turtle comprises especially the dorsal
      column nuclear complex (DC) and the solitary nucleus (Sol). The fibers arising
      from the DSM ascended ipsi- and contralaterally via the lateral and the ventral
      fiber tracts respectively. These tracts could not be assigned clearly to
      particular target areas except that the dorsal thalamic regions presumably
      receive their afferents exclusively from the lateral tract. The efferent
      projections to rhombencephalic and mesencephalic regions were restricted
      essentially to the nucleus visceralis secundarius, the nucleus profundus
      mesencephalicus and the nucleus interstitialis commissuralis posterior.
      Diencephalic target areas were found in the hypothalamus, the nucleus
      suprapeduncularis, the nucleus reuniens, the rostral perirotundal region and the
      area triangularis. Most impressive were the telencephalic projections to the
      areas c, d and h. Unlike the thalamic projections which were predominantly
      labeled ipsilaterally, the telencephalic target regions were more heavily
      involved contra- than ipsilaterally. Area d, in addition, gave rise to a
      predominantly ipsilateral projection to DSM. Other areas reciprocally connected
      with DC and/or Sol were the periventricular and intermediate regions of the
      hypothalamus, the nucleus interstitialis commissuralis posterior, the nucleus
      visceralis secundarius and the nucleus profundus mesencephali. A major descending
      projection originated from the griseum centrale (including the nucleus laminaris
      of the torus semicircularis), while minor areas of origin, apart from isolated
      reticular cells, were the nucleus and the interstitial nucleus of the fasciculus
      longitudinalis medialis, the red nucleus, the locus coeruleus and the raphe
      nuclei. The demonstrated projections were discussed in regard to their relations
      to DC and/or Sol and compared with corresponding connections in birds and
      mammals.

PMID- 7517416
TI  - A light and electron microscopical localisation of the superior salivatory
      nucleus of the rat.
AB  - The present study localised the superior salivatory nucleus (SSNc) in the
      reticular formation in rats using the retrograde axonal transport of fluorogold
      (FG). An ultrastructural study using the retrograde transport of horseradish
      peroxidase (HRP) was also carried out. After FG or cholera toxin conjugated-HRP
      (CT-HRP) injections into the lingual nerve, the labelling of SSNc in both the
      experiments was comparable. The retrogradely labelled cells were located in the
      ipsilateral parvocellular reticular formation (PCRt), dorsolateral to the facial
      nucleus and medial to the nucleus of the spinal tract of the trigeminal nerve.
      The rostrocaudal extent of the nucleus was about 0.9-1.05 mm, between the levels
      of the ascending facial nerve fibres caudally and the root of the facial nerve
      rostrally. The number of cells labelled was between 300-360, most of them being
      small to medium sized (14 x 22 mm) and appeared fusiform or polygonal. In rats
      receiving intraglandular injections of the tracers, the localisation and the
      rostrocaudal extent of the SSNc were similar, but the number of its containing
      labelled cells was only about 1/2 of the above. The SSNc cells that supplied the
      intra-glandular submandibular ganglion were not topographically arranged. On
      electron microscopy, the SSNc cells showed the typical features of preganglionic
      autonomic neurons. The cells contained a prominent round or oval nucleus. Their
      cytoplasm was rich in organelles especially conspicuous was the aggregations of
      the cisternae of rough endoplasmic reticulum in distinct clumps. In the neuropil
      between the SSNc cells were present numerous dendrites, axons, axon terminals and
      neuroglial cells. Most of the axon terminals contained predominantly round
      agranular vesicles with a few dense-cored or flattened agranular vesicles. The
      majority of the synapses associated with the HRP-labelled SSNc cells were on the
      dendrites with occasional axosomatic or axoaxonal synaptic contacts. A remarkable
      feature was the occurrence of synaptic contacts between HRP-labelled axons and
      some labelled soma.

PMID- 7517418
TI  - Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on
      human leukocytes.
AB  - Recirculation of mouse lymphocytes to the gut involves binding of the lymphocyte
      integrin alpha 4 beta 7 to the mucosal vascular addressin, MAdCAM-1. In humans,
      indirect evidence suggests that CD4+ T cells that express high levels of alpha 4
      beta 7 migrate selectively to the gut. We now report that human adult blood CD8+
      T cells and B cells, like CD4+ T cells, have heterogeneous expression of alpha 4
      beta 7. In contrast, NK cells, eosinophils, and newborn blood T and B cells have
      relatively homogeneous expression of alpha 4 beta 7. CD4+ and CD8+ T cell
      expression of alpha 4 beta 7 was related to age, CD45RA expression, and integrin
      beta 1 (CD29) expression, suggesting that alpha 4 beta 7 expression changes after
      primary activation of CD4+ and CD8+ T cells in vivo. To directly determine
      whether human alpha 4 beta 7 mediates adhesion to MAdCAM-1, we performed in vitro
      adhesion assays with two alpha 4 beta 7+ human lymphoma cell lines. The results
      indicate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alpha 4
      beta 1 is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn2+, whereas
      adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at
      least two distinct functional states. The ability of lymphocytes to bind to
      MAdCAM-1 and recirculate to mucosal organs is likely to be influenced both by the
      level of alpha 4 beta 7 expression and by the functional state of the alpha 4
      beta 7 molecule.

PMID- 7517420
TI  - Cross-linking CD40 on human B cell precursors inhibits or enhances growth
      depending on the stage of development and the IL costimulus.
AB  - The function of the cell surface molecule CD40 on B cell precursors (BCP) is not
      well understood. We now report studies using the L cell/CD40 system (anti-CD40
      mAb immobilized on CD32+ mouse L cells) to assess the potential function of CD40
      during human B cell ontogeny. Stimulation of human B lineage cells with IL-4 in
      the L cell/CD40 system yielded a hierarchy of responsiveness: high density
      tonsillar B cells > fetal splenic B cells > fetal bone marrow surface Ig+
      immature B cells > fetal bone marrow surface Ig- BCP. Using a microsphere/flow
      cytometry growth quantitation assay, we found that substituting IL-3 for IL-4 in
      the L cell/CD40 system provided a stronger growth stimulus for fetal bone marrow
      BCP and immature B cells. We also found that FACS-purified fetal bone marrow
      CD10+/CD34+/CD40+/cytoplasmic mu- pro-B cells responded maximally to IL-3 plus IL
      7. Surprisingly, anti-CD40 inhibited the pro-B cell response to IL-7. In
      contrast, FACS-purified fetal bone marrow CD10+/CD34-/CD40+/cytoplasmic mu+ pre-B
      cells were essentially nonresponsive to IL-3, IL-7, or anti-CD40 alone, but were
      uniquely responsive to IL-3 plus anti-CD40. B-lineage cells derived after 14 days
      from IL-7-stimulated pro-B cells were predominantly CD19+/L chain-, whereas pre-B
      cells stimulated with IL-3 plus anti-CD40 were predominantly CD19+/L chain+. The
      L chain+ cells from pre-B cell cultures were both mu+/delta+ and mu-/delta+. Our
      results demonstrate that the response to CD40 signaling depends upon the BCP
      developmental stage and the IL costimulus, and indicate that normal human pro-B
      cells and pre-B cells have different growth factor requirements.

PMID- 7517421
TI  - T lymphocyte T cell-B cell-activating molecule/CD40-L molecules induce normal B
      cells or chronic lymphocytic leukemia B cells to express CD80 (B7/BB-1) and
      enhance their costimulatory activity.
AB  - Activation-induced cell surface molecules are involved in mediating bidirectional
      T-B lymphocyte signaling that is important in the induction of T or B lymphocyte
      effector functions. In this regard, T-BAM/CD40-L is an activation-induced CD4+ T
      cell surface molecule known to be important in inducing B cell effector
      functions. This report demonstrates that T-BAM/CD40-L molecules on a Jurkat T
      cell leukemia subclone (D1.1) or nonlymphoid 293 kidney cell transfectants induce
      B cells or B-CLL cells to express CD80 (B7/BB-1) in a manner that is specifically
      inhibited by anti-T-BAM/CD40-L mAb 5C8. Because activation-induced B cell surface
      molecules, such as CD80, deliver costimulatory signals to T cells that augment T
      cell proliferation, the functional costimulatory capacity of T-BAM/CD40-L-primed
      B cells and B-CLL cells was studied. T-BAM/CD40-L-primed B cells or B-CLL cells
      augment the proliferative responses of allogenic T cells. Furthermore, T-BAM/CD40
      L priming is specifically inhibited by mAb 5C8. Together, these studies
      demonstrate that T-BAM/CD40-L induces CD80 expression on resting B cells or B-CLL
      cells. Moreover, T-BAM/CD40-L signaling enhances B cell costimulatory capacity.
      These studies suggest that T-BAM/CD40-L molecules not only induce B cell
      differentiative processes that result in Ab secretion, but also enable B cells to
      prime Ag-specific T cells for subsequent clonal expansion.

PMID- 7517422
TI  - Identification of a structural epitope by using a peptide library displayed on
      filamentous bacteriophage.
AB  - The screening of phage-displayed random peptide libraries has recently emerged as
      a powerful technique for probing Ab-Ag interactions. We have used this method to
      identify the epitope recognized by a mAb, CB5B10, raised against plasminogen
      activator inhibitor type-1 (PAI-1). Two phage libraries, displaying random
      hexapeptides with or without flanking cysteine residues, were screened for
      binding to mAb CB5B10. The selected phages were shown to contain similar peptide
      sequences, all of which were flanked by cysteines. When compared with the crystal
      structure of PAI-1, the selected peptides closely resemble the sequence of a
      solvent-exposed loop connecting the COOH-terminal of an alpha-helix at Phe114 to
      a beta-sheet at Ser119. Because of the constraints imposed by the flanking
      cysteine residues, the selected peptides appear to mimic the structure and the
      sequence of the PAI-1 epitope. Specific contacts between the amino acids
      displayed by the phage and the mAb were explored using site-directed mutants of
      the phage peptide. The effects of these substitutions on binding to the mAb
      correlated well with the accessibility of the corresponding residues in the PAI-1
      epitope. This is the first example of the use of phage-displayed peptide
      libraries to identify a structural epitope.

PMID- 7517419
TI  - TNF-alpha associated with fibronectin enhances phorbol myristate acetate- or
      antigen-mediated integrin-dependent adhesion of CD4+ T cells via protein tyrosine
      phosphorylation.
AB  - The effects of cytokines on immune cells may be influenced by their milieu, such
      as the extracellular matrix (ECM), in the vicinities of which cytokines and
      inflammatory cells interact and function. Previously, we demonstrated that TNF
      alpha bound to fibronectin (FN) and augments the level of adhesion of activated
      CD4+ cells. Herein, we examined the mechanisms of this pro-adhesive activity of
      TNF-alpha and its putative physiologic consequences using human or rat CD4+
      cells. A brief exposure of CD4+ cells to low dosages of soluble TNF-alpha or of
      FN- or laminin-bound TNF-alpha synergized with PMA to enhance the integrin
      mediated binding of CD4+ cells to these immobilized ECM moieties. TNF-alpha
      enhanced adhesion of CD4+ cells did not delay or inhibit the subsequent
      detachment of the cells from the substrate, and adhesion was increased provided
      the cells were treated with TNF-alpha immediately after their exposure to PMA.
      This indicates that the enhancing effect of TNF-alpha requires a previous
      activation of the cells. When TNF-alpha was immobilized on FN, less TNF-alpha was
      required to induce CD4+ cell binding to FN. Soluble, and to a greater extent FN
      bound, TNF-alpha synergizes with PMA to intensify protein tyrosine
      phosphorylation in FN-bound CD4+ cells, and this effect of TNF-alpha was
      inhibited by inhibitors of tyrosine kinase. That FN-bound or soluble TNF-alpha
      also amplified the binding of an Ag-specific autoimmune rat T cell line to
      immobilized FN, emphasizes the physiologic relevance of our findings. Thus, the
      signal transduction and cell adhesive properties of ECM glycoproteins may be
      modulated upon their association with TNF-alpha, and matrix-linked TNF-alpha may
      recruit and direct immune cells to inflammatory sites.

PMID- 7517423
TI  - Dual regulation of cytosolic phospholipase A2 in mast cells after cross-linking
      of FC epsilon-receptor.
AB  - We have reported previously that cultured mast cells (MC) express three discrete
      phospholipases A2 (PLA2s), one of which corresponds to arachidonoyl-preferential
      cytosolic PLA2 (cPLA2). In the present study, we investigated the possible role
      of cPLA2 in eicosanoid synthesis by activating mouse bone marrow-derived mast
      cells (BMMC) through cross-linking of the high affinity IgE receptor (Fc epsilon
      RI) with a specific Ag. BMMC released arachidonic acid within 2 min after Fc
      epsilon RI cross-linking. A rapid, transient phosphorylation of cPLA2 was
      observed after Fc epsilon RI cross-linking, reaching the maximum within 2 min,
      and accompanied by an increase of cPLA2 activity in the cell lysate. Exposure of
      BMMC to the IgE-Ag for longer periods resulted in a time-dependent increase of
      the cPLA2 protein. The increase was detected within 10 h after stimulation and
      reached the maximum within 30 h. Dexamethasone inhibited the Ag-stimulated cPLA2
      induction significantly. cPLA2 activity in cells stimulated for 24 h was
      increased significantly, and suppressed in cells treated with dexamethasone. When
      the cells were exposed to IgE-Ag for 36 h and then challenged with a secondary
      agonist, thrombin, arachidonate release was augmented significantly in comparison
      with cells without the Ag pretreatment. Thus, cPLA2 activation in BMMC by short
      term exposure to the Ag might be regulated by post-Fc epsilon RI modification
      (phosphorylation) of pre-existing enzyme, whereas that observed after long term
      exposure might be explained by the increase in cPLA2 protein.

PMID- 7517424
TI  - ME1 epitope of HLA-B27 confers class I-mediated modulation of gram-negative
      bacterial invasion.
AB  - We have previously demonstrated that the presence of the MHC class I molecule,
      HLA-B27, on the surface of transfected fibroblasts differentially alters Gram
      negative bacterial invasion as compared with class I alleles that are not
      implicated in the seronegative spondyloarthropathies. We have now extended this
      analysis to show that fibroblasts transfected with HLA-B7, a cross-reactive
      allele with HLA-B27, also demonstrate a similar altered bacterial invasion
      phenotype. The decrease in the ability of the bacteria to penetrate the HLA-B27
      and HLA-B7 transfectants is an invasion-mediated event, as demonstrated by
      differential invasion events using Escherichia coli transfected with the inv gene
      of Yersinia enterocolitica. The lysine at position 70, although unique to the HLA
      B27 subtypes, is shown to be not involved in mediating the decrease in invasion.
      However, the ME1 epitope is the critical factor in determining allele-specific
      alteration in invasion on the basis of the following: 1) ME1 mAb preincubation
      reverses the decrease; 2) ME1-binding alleles act like HLA-B27; 3) a class I
      allele that is intermediate in ME1 binding (HLA-B14) also demonstrates a relative
      decrease in invasion; and 4) mutation at residue 67 (C-->Y) in HLA-B27, which
      eliminates the ME1 epitope, normalizes the decreased invasion seen in the native
      HLA-B27-transfected cells. Thus, the ME1 epitope relates to the disease
      susceptibility for reactive arthritis that is conferred by both HLA-B27 and cross
      reactive group Ags.

PMID- 7517425
TI  - Epitope and functional specificity of peripheral tolerance induction in
      experimental autoimmune encephalomyelitis in adult Lewis rats.
AB  - Intravenous treatment of Lewis rats with neuroantigen-coupled splenocytes 7 days
      before the induction of experimental autoimmune encephalomyelitis with guinea pig
      myelin basic protein (GP-MBP) resulted in a significant reduction of both the
      incidence and severity of clinical disease. To test the epitope and functional
      specificities of the unresponsiveness, splenocytes (SP) coupled with the major
      encephalitogenic MBP determinant, GP-68-86, were compared with those coupled with
      intact GP-MBP for the ability to down-regulate clinical disease and Ag-specific T
      cell responses (proliferation, cytokine production, and delayed-type
      hypersensitivity) in animals primed with either intact GP-MBP/CFA or GP-68
      86/CFA. GP-MBP-SP and GP-68-86-SP were equally efficient at significantly
      inhibiting clinical disease in animals primed with GP-68-86/CFA. In contrast,
      tolerization with intact GP-MBP-SP was significantly more efficient than that
      with GP-68-86-SP at reducing disease incidence and severity in GP-MBP/CFA-primed
      animals, which indicates a role for secondary (cryptic) encephalitogenic epitopes
      in GP-MBP-induced disease. By testing a panel of GP-68-86 peptides that contained
      conservative amino acid substitutions at either position 75 (A75) or 80 (P80) or
      at both, residues that previously had been shown to be TCR contact residues, for
      their ability to inhibit experimental autoimmune encephalomyelitis induction,
      were assessed for the fine specificity of tolerance induction. None of the
      substituted peptides were capable of affecting the course of paralytic disease
      that had been induced by sensitization with the native GP-68-86 epitope, but all
      significantly reduced a milder form of the disease that had been produced by
      priming with the (A75,P80) 68-86 substituted peptide. With regard to the
      functional specificity of tolerance induction, lymph node T cells derived from
      either GP-MBP-SP- or GP-68-86-SP-treated animals exhibited a marked reduction in
      both proliferation and production of Th1-derived cytokines (IL-2, IFN-gamma, and
      lymphotoxin/TNF-alpha) in response to either GP-MBP or GP-68-86 in culture. In
      contrast, no consistent significant differences in delayed-type hypersensitivity
      responses were observed in any of the experimental groups relative to controls.
      Histologic examination of central nervous system tissues from the tolerant and
      control groups revealed significantly reduced, but still demonstrable, levels of
      perivascular infiltration even in asymptomatic animals.

PMID- 7517428
TI  - Managing a palliative oncology program: the role of a business plan.
AB  - Today's health-care environment demands that palliative-care programs operate in
      a businesslike manner. This report summarizes the business plan and the process
      followed to develop the Palliative Care Program at the Cleveland Clinic
      Foundation (CCF). The benefits generated from this effort and the lessons learned
      that may be helpful to other program managers are described. By disciplining
      itself to focus on financial, marketing, and operational issues, the Palliative
      Care Program is in a better position to advance its clinical services within the
      organization and in its market area, and can thereby serve its patients more
      effectively.

PMID- 7517427
TI  - Identification of an N-terminally acetylated encephalitogenic epitope in myelin
      proteolipid apoprotein for the Lewis rat.
AB  - Proteolipid apoprotein (PLP) is a major component of the central nervous system
      myelin. As such, it is capable of inducing experimental allergic
      encephalomyelitis (EAE) in many subhuman species. On the basis of a putative MHC
      class II binding motif in Lewis rats (RT-1B1) recently identified in our
      laboratory, the present study identifies one pathogenic T cell epitope of PLP for
      the Lewis rat, located in the area between amino acid residues 217 and 240. Four
      overlapping synthetic peptides derived from this region were tested for their
      antigenicity and encephalitogenicity. Although the longer peptides could not
      induce EAE in the Lewis rats in their "theoretically" native form after
      immunization, they were endowed with encephalitogenic ability when modified by N
      terminal acetylation. All animals immunized with N-acetylated peptides PLP 217
      233 and PLP 224-240 developed inflammation in the lower spinal cord, but with
      very low incidence of clinical EAE (1 of 12). In contrast, none of the animals
      immunized with nonacetylated peptides developed either clinical or histologic
      EAE. Mild inflammation of the spinal cord was also found in two of four rats
      immunized with N-acetylated peptide PLP 220-234. The animals immunized with the
      decapeptide, N-acetylated PLP 224-233, did not develop inflammation of the spinal
      cord. Despite the low incidence of clinical disease, it was possible to generate
      vigorous T cell lines against all the peptides synthesized from this region of
      PLP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517429
TI  - Altered sexual function and decreased testosterone in patients receiving
      intraspinal opioids.
AB  - Altered sexual function has been reported in individuals addicted to opioids or
      on methadone maintenance, yet little literature is available regarding the effect
      of intraspinal opioids on libido or sex hormone levels. We evaluated sexual
      function and plasma sex hormone levels in six men treated with chronic
      intraspinal opioids. All patients had some reduction in libido and four patients
      had difficulty obtaining or maintaining an erection. These changes were noted
      within 1 month of beginning intraspinal opioid therapy. Serum testosterone levels
      ranged from 26 to 367 ng/dL (normal, 350-1500 ng/dL); the mean serum level was
      197.7 ng/dL (SD = 119.8). Serum testosterone levels and other sex hormones,
      including follicle-stimulating hormone, luteinizing hormone, sex-hormone-binding
      globulin, and prolactin, should be measured prior to and at various points during
      intraspinal opioid therapy. Patients should be queried regarding sexual function
      and should be cautioned regarding the possibility of these adverse effects prior
      to initiating spinal opioids. Supplemental testosterone should be considered to
      treat this dysfunction.

PMID- 7517426
TI  - Definition of encephalitogenic and immunodominant epitopes of guinea pig myelin
      basic protein (Gp-BP) in Lewis rats tolerized neonatally with Gp-BP or Gp-BP
      peptides.
AB  - Two distinct epitopes of guinea pig basic protein (Gp-BP), residues 72-89 and 87
      99, possess encephalitogenic activity in Lewis rats. The purpose of this study
      was to determine to what degree the 87-99 epitope functions in rats that have
      been injected with whole Gp-BP, and whether additional epitopes in Gp-BP are
      encephalitogenic. To address these questions, we induced neonatal tolerance to
      the dominant synthetic (S)72-89 peptide or to the combination of both S72-89 and
      S87-99 peptides, and evaluated resistance to experimental autoimmune
      encephalomyelitis (EAE) induced by Gp-BP, as well as T cell responses to peptides
      that encompassed most of the Gp-BP molecule. The results demonstrated that
      virtually all of the encephalitogenic activity of Gp-BP resides within the two
      described encephalitogenic epitopes. Moreover, deletion of responses to the
      dominant epitopes prompted T cell responses to other nonencephalitogenic epitopes
      of Gp-BP, a pattern of response observed previously in rats that had recovered
      from EAE and in those protected from EAE by vaccination with TCR peptides. These
      data may have relevance to human autoimmune diseases such as multiple sclerosis
      in that naturally or immunologically regulated responses to dominant epitopes
      that are likely to be encephalitogenic may be obscured by increased responses to
      relatively innocuous determinants of basic protein. Elevated responses to
      potentially pathogenic autoantigens will likely involve both types of
      determinants, thus, underscoring the importance of distinguishing
      encephalitogenic from nonencephalitogenic determinants.

PMID- 7517431
TI  - DNA found in human immunodeficiency virus type 1 particles may not be required
      for infectivity.
AB  - We have studied the presence and significance of retroviral genome-derived DNA in
      the core of human immunodeficiency virus (HIV) particles produced from
      transfections of HXB2 expression vectors in COS-7 cells and from HIV type 1 IIIB
      chronically infected H9 cells. Viruses purified by sucrose cushion centrifugation
      and treated with DNase I contained 1000-fold more viral RNA than DNA. However,
      protease-defective viruses that contained only p160gag-pol had less than 100
      times the amount of DNA in their cores than wild-type viruses suggesting that the
      p66/p51 form of reverse transcriptase was responsible for DNA transcription.
      Viruses produced by transfections in the presence of 3'-azido-3'-deoxythymidine
      (AZT) contained the viral RNA genome but only DNA of premature length because of
      the chain terminating effects of AZT. However such viruses were as infections for
      CD4+ cells as wild-type virus. We conclude that retrovirus-derived DNA in HIV-1
      particles is not required for infection and does not play a significant role in
      this process.

PMID- 7517430
TI  - High rate of nonspecific anti-hepatitis C reactivity amongst homosexual men in
      comparison with that found in other sexually active groups and blood donors.
      Viral Hepatitis and AIDS Study Group.
AB  - OBJECTIVES: To investigate the concordance of anti-hepatitis C virus (anti-HCV)
      reactivity by a second-generation enzyme immunoassay (EIA-2) and by a four
      antigen recombinant immunoblot assay (4-RIBA) in homosexual men, in comparison
      with that found in other sexually active groups and blood donors. DESIGN:
      Prospective study. SETTING: Tertiary referral centre, Seville, Spain. SUBJECTS: A
      total of 1203 subjects were studied. Eight hundred and three were sexually active
      individuals: 547 female prostitutes, 88 heterosexual men who had frequent sexual
      intercourse with prostitutes, and 168 homosexual men. All of them denied blood
      transfusion and parenteral drug use. In addition, 400 voluntary blood donors were
      selected at random. MAIN OUTCOME MEASURES: All serum samples were screened for
      anti-HCV by EIA-2 and repeatedly reactive sera were tested by 4-RIBA. Homosexual
      men were also screened for anti-human immunodeficiency virus (anti-HIV),
      hepatitis B virus (HBV) markers and gammaglobulin concentration. Finally, serum
      samples from homosexual men reactive for anti-HCV by EIA-2 were analyzed for HCV
      RNA by polymerase chain reaction (PCR). RESULTS: Concordance between EIA-2 and 4
      RIBA in female prostitutes (71.4%), clients of prostitutes (75.0%), and blood
      donors (83.3%) was significantly higher than in homosexual men (38.8%) (P <
      0.04). In this collective the concordance between 4-RIBA and PCR was 85.7% for
      positive cases and 88.8% for negative ones, and EIA-2 ratios in reactive sera
      were significantly higher in 4-RIBA confirmed cases (P < 0.0001). No correlation
      between false positive EIA-2 results and presence of HIV infection, HBV markers
      or hypergammaglobulinaemia was found in homosexual men by univariate analysis.
      CONCLUSIONS: There is a high level of non-specific anti-HCV reactivity by EIA-2
      amongst homosexual men in comparison with that found in other sexually active
      groups and blood donors. The true prevalence of HCV infection amongst homosexual
      men could be even lower than previously described.

PMID- 7517432
TI  - Hepatitis C virus particle detected by immunoelectron microscopic study.
AB  - To clarify the morphology of hepatitis C virus (HCV), an indirect immunogold
      electron microscopic study was carried out on two plasma samples with high HCV
      RNA titres using polyclonal and monoclonal antibodies specific to the putative
      HCV envelope protein. Spherical virus-like particles, 55 to 65 nm in diameter
      with spike-like projections, were found in 1.14 to 1.16 g/ml fractions after
      sucrose density gradient centrifugation. These particles were found only in HCV
      infected blood donors and had morphological features similar to those of
      flaviviruses. Moreover, these particles specifically reacted with the polyclonal
      and monoclonal antibodies to the putative HCV envelope protein. This is the first
      known report in which the morphology of the HCV particle is clearly shown.

PMID- 7517434
TI  - Sequence and expression of a baculovirus protein with antigenic similarity to
      telokin.
AB  - A protein from baculovirus-infected cells reacted with an antibody against the
      smooth muscle protein telokin. Because of this unusual similarity, the protein,
      termed telokin-like protein-20 (TLP20), was isolated and characterized. Its M(r)
      on denaturing polyacrylamide gels was 28K and the protein contained a high
      proportion of beta structure. A cDNA for TLP20 was isolated and sequenced. The 3'
      non-coding sequence contained a region of high identity with the 5' end of two
      other baculovirus genes. The 5' non-coding region contains several baculovirus
      regulatory elements. Surprisingly, the derived amino acid sequence showed no
      homologies to telokin. The cDNA was cloned into a bacterial expression vector and
      the subsequently expressed protein had a slightly lower M(r) than the native
      protein, but cross-reacted with telokin antibody. This paper reports the
      characterization of a new baculovirus protein that shares some antigenic
      similarities to the smooth muscle protein telokin.

PMID- 7517433
TI  - Sialoglycoproteins that bind influenza A virus and resist viral neuraminidase in
      different animal sera.
AB  - Sialoglycoproteins that are resistant to degradation by viral neuraminidase can
      effectively neutralize influenza A viruses, because they bind irreversibly to the
      viruses. To detect such proteins in animal sera, we developed an immunochemical
      assay based on Western blotting techniques. We assessed the binding activity of
      sialoglycoproteins in sera from nine different animals toward the A/Aichi/2/68
      (H3N2) and A/PR/8/34 (H1N1) strains of influenza virus, with or without viral and
      bacterial neuraminidase treatment. Using this assay, we found that animal sera
      contain a spectrum of sialoglycoproteins defined by differing abilities to bind
      influenza A viruses and to resist the viral neuraminidase. Structural analysis of
      these inhibitors would provide useful information for the development of anti
      influenza virus compounds.

PMID- 7517436
TI  - Hu neuronal proteins are expressed in proliferating neurogenic cells.
AB  - We have utilized immunochemical techniques to investigate the developmental
      expression of the Hu proteins, a neuron-specific family of RNA binding proteins
      in vertebrates. Previous work suggests that these proteins may play an important
      role in neuronal development and maintenance. For the present study, we developed
      a monoclonal antibody (MAb 16A11) that binds specifically to an epitope present
      in gene products of all known Hu genes, including HuD, HuC, and Hel-N1. Using
      brief pulses (1-2 h) of the DNA precursor analog bromodeoxyuridine (BrdU) in
      conjunction with MAb 16A11, we observed Hu+/BrdU+ cells in nascent sensory and
      sympathetic ganglia in vivo, and in populations of cultured neural crest cells.
      In addition, a few Hu+ cells were ambiguously BrdU+ in the neural tube. We
      conclude that Hu+ cells first appear in avian neurogenic populations immediately
      before neuronal birthdays in the peripheral nervous system, and at the time of
      withdrawal from the mitotic cycle in the central nervous system. Consistent with
      these conclusions, we have also observed neural crest-derived cells that are both
      Hu+ and in metaphase of the cell cycle. We suggest that Hu proteins function
      early in neurogenic differentiation.

PMID- 7517435
TI  - Galanin and vasoactive intestinal peptide messenger RNAs increase following
      axotomy of adult sympathetic neurons.
AB  - The adult rat superior cervical ganglion (SCG) contains low levels of galanin-
      and vasoactive intestinal peptide-(VIP) like immunoreactivity, with very few
      immunostained principal neurons. Immunoreactivity for both neuropeptides
      increases in these neurons after explantation or postganglionic axotomy in vivo.
      Northern blot analysis has demonstrated concomitant increases in mRNAs encoding
      these peptides. To localize cells in axotomized ganglia which increase their
      expression of these mRNAs, we performed in situ hybridization studies. In control
      SCG, only a few principal neurons contained mRNA for either galanin or VIP. After
      48 h in organ culture, galanin mRNA was expressed in the majority of principal
      neurons. At 48 h after in vivo axotomy of both postganglionic trunks of the SCG,
      the internal and external carotid nerves, the distribution and number of neurons,
      expressing galanin mRNA increased similarly to that seen in culture. Lesioning
      either trunk alone produced increases in galanin mRNA localized to those regions
      of the ganglion containing neurons that project into the lesioned trunk.
      Transection of the predominantly preganglionic cervical sympathetic trunk
      increased galanin mRNA expression in a small population of neurons near that
      nerve trunk. The distributions of these labeled neurons, together with previous
      neuroanatomical studies, suggests that they had been axotomized by the lesions.
      Similar studies examining VIP mRNA expression demonstrated that although
      considerably fewer VIP mRNA expressing neurons than galanin mRNA expressing
      neurons were present after axotomy, the distribution of neuropeptide mRNA
      positive cells were similar in both cases. These observations suggest that
      increases in the peptides galanin and VIP after nerve transection result from
      changes in the levels of their mRNAs in those neurons that have been axotomized.

PMID- 7517437
TI  - Female marsh wrens do not provide evidence of anatomical specializations of song
      nuclei for perception of male song.
AB  - In songbirds the forebrain nuclei HVC (high vocal center) and RA (robust nucleus
      of the archistriatum) are larger in individuals or species that produce larger
      song repertoires, but the extent to which the size of these nuclei reflects a
      need for either producing or perceiving large repertoires is unknown. We,
      therefore, tested the hypothesis that species differences in the size of song
      nuclei reflect a commitment of "brain space" to the perceptual processing of
      conspecific song. The two species of marsh wren (Cistothorus palustris western
      and eastern) provide a good test case. Western males produce larger song
      repertoires, and have larger HVC and RA than do eastern males. Female marsh wrens
      do not sing, and if they use their song nuclei to assess conspecific male song
      repertoires, then we predicted that measurable cellular and nuclear parameters of
      HVC and RA would be greater in western than eastern female wrens. For males we
      confirmed that the volumes of HVC and RA, and cellular parameters of HVC, are
      greater in western than in eastern birds. These nuclei were also considerably
      larger in males than in conspecific females. Western and eastern female wrens,
      however, did not differ in any measured parameters of HVC or RA. Females of these
      wren species thus do not provide any direct evidence of anatomical
      specializations of song nuclei for the perceptual processing of conspecific male
      song.

PMID- 7517438
TI  - Neurite outgrowth from cultured CNS neurons is promoted by inhibitors of protein
      and RNA synthesis.
AB  - We examined the effects of changes caused by the blocking of protein and RNA
      synthesis on neurite outgrowth from neurons of the central nervous system (CNS)
      in primary culture. Exposure to cycloheximide and actinomycin-D led to dramatic
      increases in the length of neurites in cultures of neurons from various rat or
      chick CNS regions. Inhibitor-induced neurite outgrowth was observed (1) from
      dopaminergic neurons in mixed cultures of the rat substantia nigra or (2) in pure
      cultures of rat and chick neurons grown on a polyornithine/laminin substratum.
      These results suggest that neurite outgrowth from CNS neurons is kept restricted,
      at least in culture, by the continuous production of a labile neurite-inhibiting
      protein intrinsic to the neurons, which rapidly decays following inhibition of
      protein or RNA synthesis.

PMID- 7517439
TI  - Spiroquinazoline, a novel substance P inhibitor with a new carbon skeleton,
      isolated from Aspergillus flavipes.
AB  - A novel substance P inhibitor, spiroquinazoline [1], was isolated from the fungus
      Aspergillus flavipes, which was originally obtained from soil. The structure of 1
      was determined by analysis of spectroscopic data and 1 was shown to contain a new
      carbon skeleton containing a spiro-carbon center. Also isolated from the same
      culture extract were the new natural product, benzodiazepiedione [3], and the
      known compounds, acyl aszonalenin [4], N-benzoyl-L-phenylalaninol, and seven
      diketopiperazines.

PMID- 7517440
TI  - Mast cells in experimental allergic encephalomyelitis: characterization,
      distribution in the CNS and in vitro activation by myelin basic protein and
      neuropeptides.
AB  - Mast cells (MC) have been implicated in the pathogenesis of experimental allergic
      encephalomyelitis (EAE). In order to further evaluate their role, several
      morphological and functional studies were performed. Semiquantitative counts of
      histological sections showed a significant reduction in MC numbers in EAE brains.
      In addition, a higher proportion of EAE MC (about 50-70%) appeared degranulated
      compared with about 20% degranulation in controls. Central nervous system (CNS)
      MC exhibited staining properties of connective tissue MC and about 98% of them,
      both in diseased and control rats, were located in the thalamus. They were not
      present in the spinal cord and did not relate to EAE lesions. In vitro incubation
      of peritoneal MC (of connective tissue phenotype) with either MBP, or with
      neuropeptides such as substance P or bradykinin resulted in release of beta
      hexosaminidase and histamine. The latter responses were similar in both EAE and
      control rats. It is suggested that the decrease in number and in granular content
      of CNS MC in EAE may reflect prior in vivo activation. The fact that MC were
      activated by MBP and by neuropeptides in vitro suggests a possible mechanism of
      MC activation in EAE.

PMID- 7517441
TI  - Pattern of nervous tissue immunostaining by human anti-glycolipid antibodies.
AB  - Immunostaining of human, bovine and rodent unfixed nervous tissue sections was
      performed in order to characterize the structures recognized by anti-glycolipid
      antibodies. Four human sera from patients, two with M-IgM and motor neuron
      syndrome or motor neuropathy and two with motor neuropathy and polyclonal IgG
      antibody activity against gangliosides (GL; i.e. GM1, GD1b, GD1a), were utilized.
      Serum from a patient with sensory neuropathy and M-IgM immunoglobulins with
      antibody activity against sulfatide (SUL) was included in this series. This study
      shows that polyclonal and monoclonal anti-glycolipid antibodies give three
      different patterns of staining. The first is cholera toxin-like showing a more
      restricted neuronal pattern of staining. The second is peanut agglutinin-like,
      which includes the carbohydrate epitope shared by a group of glycoproteins in the
      gray and white matter. The third (anti-SUL) gives a preferential myelin staining.
      However, sera with anti-GM1 and anti-SUL antibodies recognize a number of closely
      situated determinants in the gray matter of the spinal cord and in the granule
      cells, while in peripheral nerves or in neuronal cells in culture their binding
      produces a different pattern (nodes of Ranvier for anti-GL; myelin for anti-SUL).
      These findings indicate that immunohistochemistry with anti-GL and anti-SUL
      antibodies may provide information regarding the glycolipid-bearing anatomical
      structures as target antigens and further substantiate the role of these
      molecules in the pathogenesis of autoimmune neurological disorders.

PMID- 7517444
TI  - Euthanasia and the care of cancer patients.

PMID- 7517443
TI  - Prostate-specific antigen decline: a major prognostic factor for prostate cancer
      treated with radiation therapy.
AB  - PURPOSE: To assess the prognostic significance of serum prostate-specific antigen
      (PSA) in the monitoring of patients with localized prostate cancer treated with
      primary radiation therapy, we analyzed the data from 179 patients treated at our
      institution between 1987 and 1990. PATIENTS AND METHODS: One hundred seventy-nine
      previously untreated patients received radiation at 69 Gy to the prostate with
      curative intent for prostate adenocarcinoma. The median follow-up duration is now
      41 months. PSA levels were measured before radiotherapy and then evaluated
      periodically. RESULTS: Baseline levels were greater than 4 ng/mL in 83% of cases
      and were significantly correlated with clinical tumor stage (P = .002). Six
      months after completion of therapy, PSA values had returned to normal in 53% of
      the patients with initially elevated values. At the time of analysis, 32 patients
      have relapsed, including three of 30 patients (10%) with normal initial and 6
      month values, five of 79 patients (6%) with initially elevated but normal 6-month
      values, and 24 of 69 patients (35%) with persistently elevated PSA levels at 6
      months. Actuarial 4-year relapse-free survival was significantly correlated with
      initial and 6-month PSA values (84% in patients with normal 6-month values v 60%
      in patients with persistently elevated levels). Furthermore, when the relative
      decline between initial and 6-month PSA values exceeded 50%, the crude rate of
      recurrence was 14% as opposed to 34% when it failed to exceed 50%. The 4-year
      relapse-free survival rates were 77% and 59%, respectively (P = .008). By
      multivariate analysis restricted to the patients with elevated baseline PSA
      levels, the rate of decline of PSA values reached the highest prognostic
      significance (P < .0001). Age at diagnosis, clinical tumor stage, and Gleason
      score only reached statistical significance in univariate analysis. CONCLUSION:
      PSA values are of major prognostic significance in assessing the 4-year results
      of radical radiation therapy for localized prostate cancer. The rate of decline
      of PSA values is the strongest predictor of outcome and might help to identify a
      subset of patients with poorer prognosis who may benefit from early hormonal
      therapy.

PMID- 7517442
TI  - MACOP-B versus ProMACE-MOPP in the treatment of advanced diffuse non-Hodgkin's
      lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma
      Cooperative Study Group.
AB  - PURPOSE: The aim of our study was to compare in a multicentric randomized trial
      two regimens widely used in the treatment of advanced-stage intermediate- to high
      grade non-Hodgkin's lymphoma and to assess whether a third-generation regimen
      (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine,
      prednisone, and bleomycin [MACOP-B]) was superior to a second-generation regimen
      (procarbazine, methotrexate with leucovorin, doxorubicin, cyclophosphamide, and
      etoposide [ProMACE-MOPP]). PATIENTS AND METHODS: Between January 1987 and August
      1991, 221 patients with diffuse intermediate- to high-grade non-Hodgkin's
      lymphoma (Working Formulation groups F, G, H, and K), stage II bulky (> 10 cm),
      III, or IV, were randomized by the Non-Hodgkin's Lymphoma Cooperative Study Group
      (NHLCSG) to receive ProMACE-MOPP for six cycles or MACOP-B for 12 weeks.
      Survival, progression-free survival, and disease-free survival were determined,
      and multivariate analysis of prognostic factors was performed. RESULTS: In the
      two groups of patients, there was no significant difference in terms of complete
      remission (CR) rate (49.1% with ProMACE-MOPP and 52.3% with MACOP-B), 3-year
      overall survival rate (45.2% with PROMACE-MOPP and 52.3% with MACOP-B), and 3
      year progression-free survival rate (36.4% with ProMACE-MOPP and 36.1% with MACOP
      B). In terms of toxicity, no significantly greater toxicity occurred in either
      arm. Overall toxicity was acceptable. The most frequent side effects were grade
      II through IV leukopenia, infection, mucositis, and anemia. Treatment-related
      deaths were equally distributed. CONCLUSION: No significant differences in terms
      of efficacy and/or toxicity between ProMACE-MOPP and MACOP-B are evident. These
      results are consistent with recent randomized trials showing that the new
      generation aggressive regimens are no better than previous ones.

PMID- 7517445
TI  - Maternal estimates of developmental age in preschool children.
AB  - OBJECTIVE: To investigate the accuracy of maternal estimates of developmental age
      in preschool children with suspected developmental delay. METHODS: In a sample of
      139 preschool children, aged 5 to 60 months, mothers were asked before evaluation
      to estimate the developmental age of their child. Maternal estimates were
      converted to a developmental quotient (DQ) and compared with results from
      standardized tests of cognitive functioning, adaptive abilities, expressive and
      receptive language, and visual-motor skills. RESULTS: A high correlation was
      found (r = 0.82; p < 0.0001) between maternal-estimate DQ and actual DQ (mean of
      test scores). Most mothers estimated within 15% of their child's actual
      functioning, and 84% of mothers estimated within +/- 5 months of actual
      functioning. Multiple regression found no factors that would identify mothers who
      were more or less accurate in estimating developmental age. Maternal-estimate DQ
      was sensitive (83%) and specific (83%) for mental retardation. CONCLUSION:
      Maternal estimates provide an accurate measure of developmental functioning and
      could be successfully incorporated into routine developmental surveillance of
      preschool children.

PMID- 7517446
TI  - Severe respiratory failure in neonates: mortality and morbidity rates and
      neurodevelopmental outcomes.
AB  - OBJECTIVE: To compare the survival, neurodevelopmental, and health outcomes of
      children with severe respiratory illness treated with and without extracorporeal
      membrane oxygenation (ECMO). DESIGN: Prospective collection of clinical and
      demographic data of all neonates reaching illness severity criteria, with follow
      up at 8 and 20 months of age. Patients were assigned to treatment by the
      attending physician. PATIENTS: Consecutive sample of 74 neonates during a 24
      month period with an alveolar-to-arterial gradient exceeding 620 for 8 or more
      hours. RESULTS: Eighteen (69%) of 26 neonates treated with conventional therapy
      survived to 20 months, in comparison with 43 (90%) of 48 neonates treated with
      ECMO. The conventionally treated group had significantly more chronic lung
      disease, longer duration of oxygen therapy, more chronic reactive airway disease,
      and more rehospitalizations than those treated with ECMO. Hospital charges were
      similar in the two groups. Macrocephaly was noted in 24% of those treated with
      ECMO and in none of the conventional group. Of those completing evaluation, 4
      (24%) of 17 conventionally treated survivors and 20 (26%) of 38 ECMO-treated
      survivors had neurodevelopmental impairment. CONCLUSION: Survivors of severe
      neonatal respiratory illness have significant pulmonary and neurodevelopmental
      impairment, regardless of the treatment used. Neonates treated with ECMO had
      neurodevelopmental outcomes similar to those of patients treated conventionally,
      but better pulmonary outcomes.

PMID- 7517447
TI  - Distribution and protein binding of FK506, a potent immunosuppressive macrolide
      lactone, in human blood and its uptake by erythrocytes.
AB  - The distribution of FK506 in the blood was estimated in-vitro. At a drug level of
      5 ng mL-1, FK506 mainly distributed in erythrocytes (95-98%) in dog, monkey and
      human blood, and its distribution was affected by drug concentration,
      temperature, and haematocrit values. In erythrocytes most of FK506 was
      distributed in cytoplasmic components and was bound strongly to a protein having
      a molecular weight of 10-11 kDa. The molecular weight of this protein agrees with
      FK506-binding protein found in various cells. Greater than 98.8% of FK506 was
      bound to the plasma proteins in all species studied. FK506 bound to various
      plasma proteins such as lipoproteins, globulins, alpha 1-acid glycoprotein and
      albumin.

PMID- 7517448
TI  - HIV-1 syncytium-inducing phenotype, virus burden, codon 215 reverse transcriptase
      mutation and CD4 cell decline in zidovudine-treated patients.
AB  - The variable rate of disease progression in HIV-1-infected patients treated with
      zidovudine may be related to certain viral characteristics, such as, antiviral
      drug resistance, virus burden, and viral syncytium-inducing (SI) capacity. Thirty
      two HIV-1-infected patients treated with zidovudine (mean of 34 months) were
      studied to determine the relationship of SI phenotype and the codon 215 pol gene
      mutation (a marker of zidovudine resistance) to virus burden and CD4 cell
      decline. Patients with SI strains and the codon 215 mutation in their proviral
      DNA had a 54% decline in CD4 cells and a virus burden of 21,480 proviral DNA
      copies/10(6) CD4 cells. In contrast, patients with non-SI (NSI) strains and wild
      type at codon 215 had a 10% increase in CD4 cells and had a viral burden 1/46
      that of patients with SI and the 215 mutation. Among patients with NSI strains,
      changes in CD4 cells depended on the presence of the codon 215 mutation (-160 CD4
      cells/microliters), compared with those wild-type at codon 215 (+28 CD4
      cells/microliters) (p < 0.01). There was a concordant rise in virus burden
      between proviral DNA and plasma HIV RNA depending on HIV phenotype and genotype.
      Using multiple linear regression, SI phenotype and the codon 215 mutation were
      found to independently predict CD4 cell decline and increased virus burden in
      zidovudine-treated patients.

PMID- 7517449
TI  - P-type calcium channels in rat neocortical neurones.
AB  - 1. The high threshold, voltage-activated (HVA) calcium current was recorded from
      acutely isolated rat neocortical pyramidal neurones using the whole-cell patch
      technique to examine the effect of agents that block P-type calcium channels and
      to compare their effects to those of omega-conotoxin GVIA (omega-CgTX) and
      nifedipine. 2. When applied at a saturating concentration (100 nM) the peptide
      toxins omega-Aga-IVA and synthetic omega-Aga-IVA blocked 31.5 and 33.0% of the
      HVA current respectively. 3. A saturating concentration of nifedipine (10 microM)
      inhibited 48.2% of the omega-Aga-IVA-sensitive current, whereas saturating
      concentrations of both omega-Aga-IVA (100 nM) and omega-CgTX (10 microM) blocked
      separate specific components of the HVA current. 4. Partially purified funnel web
      spider toxin (FTX) at a dilution of 1:1000 blocked 81.4% of the HVA current and
      occluded the inhibitory effect of omega-Aga-IVA. Synthetic FTX 3.3 arginine
      polyamine (sFTX) at a concentration of 1 mM blocked 61.2% of the HVA current
      rapidly and reversibly. The effects of sFTX were partially occluded by pre
      application of omega-Aga-IVA. We conclude that neither FTX nor sFTX blocked a
      specific component of the HVA current in these cells. 5. In view of the
      specificity of omega-Aga-IVA for P-type calcium channels in other preparations
      and for a specific component of the HVA current in dissociated neocortical
      neurones we conclude that about 30% of the HVA current in these neurones flow
      through P-channels.

PMID- 7517450
TI  - Capsaicin-sensitive stretch responses in ferret trachealis muscle.
AB  - 1. Stretch-induced electrical and mechanical responses in segments of ferret
      trachealis muscle were studied. Stretches and post-stretch length changes were
      quantified by measuring distances between two marker spheres placed on the muscle
      surface. Electrical responses were determined by measuring membrane potential in
      the muscle cell syncytium. 2. Smooth muscle mechanical and electrical responses
      to the stretch manoeuvre were characterized by an initial shortening and
      depolarization phase and a reversal-repolarization phase. Both phases were
      resistant to atropine and tetrodotoxin. During the initial phase, the membrane
      depolarized to potentials as low as -20 mV. For stretches to 1.0 Lmax, from a
      holding length of 0.75 Lmax, 50% repolarization occurred at 6.8 +/- 0.4 min post
      stretch; 50% reversal of shortening of the stretched segment occurred at 6.9 +/-
      0.8 min post-stretch. 3. Depolarizing currents generated within muscle cells in
      the stretched segment spread into cells in non-stretched muscle. Space constants
      in the transverse and longitudinal directions averaged 480 +/- 46 and 146 +/- 50
      microns, respectively. 4. During infusion of capsaicin (10 microM), muscle cells
      depolarized by 5.5 +/- 2.3 mV. Maximal depolarization was achieved after 15-20
      min. After inhibition of neutral enkephalinase, capsaicin-evoked depolarization
      occurred more rapidly. Muscles depolarized by 11.2 +/- 2.1 mV after about 10 min
      of capsaicin and then slowly repolarized during continued treatment. When muscle
      segments were stretched during administration of capsaicin, the initial phase was
      similar to that observed before capsaicin, but the reversal-repolarization phase
      was prolonged. Following wash exposure to capsaicin, maximal stretch-induced
      depolarization was unchanged, but the time for 50% repolarization (t50
      repolarization) decreased from the pre-capsaicin value of 8.4 +/- 1.3 to 4.1 +/-
      0.5 min. The t50-reversal of stretch-evoked muscle shortening decreased to 54% of
      control values. 5. Short exposures (< 2 min) to substance P (SP, 1-7.5 microM)
      depolarized smooth muscle cells. Maximal depolarization was delayed, and occurred
      after [SP] had decreased to < 10 nM. Repolarization was delayed as long as 6 min
      following wash-out of SP. Stretches performed when SP-induced depolarization had
      nearly reversed showed no changes in the initial mechanical or electrical
      responses, but t50-repolarization increased to 162% of control values. 6.
      Immunochemical studies showed networks of neurones which react with SP
      antibodies. 7. These findings suggest that stretch induces SP release from
      capsaicin-sensitive C fibres, and that released SP affects smooth muscle ionic
      mechanisms which control and delay the reversal of stretch-induced membrane
      depolarization and shortening.

PMID- 7517451
TI  - Increased submucosal factor XIIIa-positive dendrocytes in oral lichen planus.
AB  - Factor XIIIa+ "dendrocytes", normal residents of the submucosa and dermis, are a
      morphologically and phenotypically distinctive subset of the monocyte-macrophage
      system. Because these cells are believed to participate in the regulation of
      immune responses, we postulated that they may play a role in the pathogenesis of
      lichen planus, a condition of immune dysregulation. Tissue sections of oral
      lichen planus were evaluated immunohistochemically for evidence of differences in
      dendrocyte populations in lesional and non-lesional areas from the same patient.
      In addition to factor XIIIa, sections were stained for antigens (CD68, S-100
      protein, CD36) that may be expressed by other cells that occasionally exhibit
      dendritic profiles. CD18 (found on leukocytes and dendrocytes) and its ligand
      ICAM-1 (intercellular adhesion molecule) were also identified in sections to
      determine if these antigens are operative in lichen planus. Results showed that
      XIIIa+ dendrocytes were significantly increased in number (and size) in lichen
      planus. The mean number of dendrocytes in connective tissue subjacent to basement
      membrane (0.064 mm2) was 27 in lichen planus as compared to 10 in adjacent
      unaffected tissue. Similar increases were also evident in connective tissue deep
      to this zone (mean of 20 dendrocytes vs. mean of 8). CD68+ macrophages were also
      abundant in the lichen planus infiltrate, and S-100+ connective tissue cells were
      frequently seen. CD36+ dendritic cells were seen in relatively small numbers in
      the same sites where dendrocytes were found. ICAM-1+ connective tissue dendritic
      cells of undetermined lineage were also evident in the diseased areas.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7517452
TI  - Comparison of a lesion-inducing isolate and a non-lesional isolate of Candida
      albicans in an immunosuppressed rat model of oral candidiasis.
AB  - Two distinct strain-related patterns of organism-host interaction on dorsal
      tongue of immunocompetent rats have been identified for Candida albicans: some
      isolates induce mucosal lesions, while other isolates penetrate the keratin layer
      but do not produce a lesion. This study examined the behavior of each of the two
      types of isolates in a cyclosporin-immunosuppressed rat model. Groups B (normal)
      and D (cyclosporin) were orally inoculated with a lesion-inducing isolate of C.
      albicans, while a non-lesional isolate was given to Groups A (normal) and C
      (cyclosporin). A typical dorsal tongue lesion developed in 4/18 rats in Group B
      and in 13/16 in Group D (P = 0.00267). No significant difference in infection
      rate between the normal and cyclosporin-treated animals was seen for the non
      lesional isolate. The lack of a host inflammatory response associated with the
      non-lesional isolate may represent an ecologic advantage for the organism.

PMID- 7517454
TI  - Identification of a grpE heat-shock gene homolog in the archaeon Methanosarcina
      mazei.
AB  - A grpE heat-shock gene was found by sequencing in the genome of the methanogenic
      archaeon Methanosarcina mazei S-6. It is the first example of grpE from the
      phylogenetic domain Archaea. Since the other seven sequenced homologs are from
      the domain Bacteria, it may be concluded that grpE appeared early in evolution,
      before the two domains separated. The archaeal grpE is located in the dnaK locus,
      431 base-pairs upstream of dnaK, which is followed downstream by the dnaJ gene.
      The organization of these three genes is known for Bacillus subtilis, Clostridium
      acetobutylicum, Borrelia burgdorferi and Mycobacterium tuberculosis. The archaeal
      locus organization, grpE-dnaK-dnaJ, is similar to that of the former three
      bacteria, but different from that of M. tuberculosis. This, and sequence
      homologies, suggest that the M. tuberculosis GrpE belongs, together with the
      Streptomyces coelicolor homolog, to a subgroup of the GrpE proteins. The M. mazei
      grpE gene encodes a protein of 209 amino acid residues. The deduced amino acid
      sequence shows 28.2 to 34.6% identities, and 50.3 to 58.9 similarities
      (identities plus conservative substitutions) with the other six complete GrpE
      sequences available. These percentages fall within the range observed for the
      other GrpEs. Two regions in the second and fourth quarters of the GrpE molecule
      show higher homology, particularly in three stretches of nine, six and nine amino
      acid residues, respectively. The archaeal gene uses all codons but three, whereas
      the bacterial homologs lack higher numbers of codons. The M. mazei grpE responded
      to heat-shock by increasing transcription, in a manner similar to that of the
      nearby heat-shock gene dnaK.

PMID- 7517455
TI  - Toxic neurofilamentous axonopathies and fast axonal transport. V. Reduced
      bidirectional vesicle transport in cultured neurons by acrylamide and
      glycidamide.
AB  - Fast axonal transport deficiencies as mechanisms of action of acrylamide in
      producing axonal degeneration are under evaluation. The current study determines
      the effects of acrylamide and several analogues on the number of vesicles moving
      within the neurite processes of cultured rat embryonic neurons. Acrylamide
      produced severe, concentration-dependent (0.25-1.0 mM) and time-dependent (0-60
      min) reduction in the quantity of vesicles translocated in both the anterograde
      and retrograde directions. Glycidamide, a potential neurotoxic metabolite of
      acrylamide, produced a time-dependent but not a concentration-dependent (in the
      0.25-1.0 mM range) reduction in bidirectional transport. Based on inhibition at
      60 min, glycidamide was estimated to be 4 times more potent than acrylamide in
      altering transport. Propionamide, a C1-C2 saturated nonneurotoxic acrylamide
      analogue, had no effect on axonal transport. While a tendency for methylene
      bisacrylamide (MbACR) to reduce vesicle transport was noted, at the concentration
      used no statistically significant differences from control were observed. The
      data support the correlation between toxicant-induced fast anterograde and
      retrograde axonal transport reductions and axonal degeneration produced by
      acrylamide and its analogues.

PMID- 7517457
TI  - Peptide bond specificity of calpain: proteolysis of human myelin basic protein.
AB  - In order to determine the peptide bond specificity of calpain, human myelin basic
      protein (HMBP) was treated with purified calpain of bovine brain. Upon
      incubation, HMBP component I (HMBP-I) was degraded into several peptides as
      demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      Component I was more susceptible to degradation than components II and III. HMBP
      degradation products were separated by high performance liquid chromatography
      (HPLC) and the cleavage sites in HMBP molecules were determined by peptide
      sequence analysis and by N- and C-terminal analyses. The major cleavage site was
      found to be 94Val-95Thr with several minor cleavages at 49Arg-50Gly, 18Ala-19Ser,
      23His-24Ala, 27Gly-28Phe, 59Asp-60Ser, 70Gly-71Ser, 97Arg-98Thr, 110Ser-111Leu,
      145Asp-146Ala, and 156Leu-157Gly. These results indicate that calpain is involved
      in the limited proteolysis of human myelin basic protein and prolonged incubation
      causes further digestion of the large peptides.

PMID- 7517453
TI  - Possible roles of insulin and insulin-like growth factors in rat preimplantation
      development: investigation of gene expression by reverse transcription-polymerase
      chain reaction.
AB  - The sensitive mRNA phenotyping technique of reverse transcription-polymerase
      chain reaction was used to demonstrate that insulin receptor mRNA is present in
      rat embryos during the preimplantation period. In addition, mRNA encoding insulin
      like growth factor (IGF) type I and type II receptors have also been detected in
      rat preimplantation embryos. IGF-I mRNA was not detected in preimplantation
      embryos but was found in oviducts and uteri of prepubertal and early pregnant
      rats. IGF-II mRNA was present in both embryos and in oviducts and uteri during
      the preimplantation period. These findings suggest that insulin and IGF-I could
      influence early embryo development in endocrine or in paracrine fashions, whereas
      IGF-II may have an additional autocrine mode of action in affecting
      preimplantation embryos in rats.

PMID- 7517456
TI  - Immunological determinants of nerve growth factor involved in p140trk (Trk)
      receptor binding.
AB  - Monoclonal anti-NGF antibodies that specifically inhibit the biological activity
      of mouse beta-NGF were used to study the structural determinants involved in the
      interaction of NGF with its receptors gp75LNGFR and Trk. None of the three
      antibodies--N60, M15, and 27/21--showed any reactivity toward denatured NGF.
      Three experimental methods--radioimmunoassay (RIA), enzyme-linked immunoassay
      (ELISA), and slot blots--detected no significant cross reactivity between the
      antibodies and BDNF or NT-3. RIA showed that M15 and N60 recognize the same or an
      overlapping antigenic site, but 27/21 recognizes a different epitope. Only 27/21,
      and not N60 or M15, immunoprecipitated beta-NGF crosslinked to LNGFR receptor.
      Thus, the epitope recognized by 27/21 does not overlap the LNGFR receptor binding
      site. N60, M15, and 27/21 all block binding of NGF to Trk in a manner consistent
      with competitive inhibition. Purified Fab fragments of N60 and M15 gave similar
      results to the intact antibodies. The other subunits present in the 7S complex of
      NGF, i.e. the alpha and gamma subunits, competitively inhibited binding of
      antibodies to beta-NGF. Only the gamma subunit inhibited phosphorylation of Trk
      and biological activity of beta-NGF. These findings suggest that the M15, N60,
      and 27/21 antibodies bind to a specific site on the surface of NGF where they
      competitively inhibit binding to the Trk NGF receptor. The region encompassing
      the N-terminus, the C-terminus, and the loop on the surface of beta-NGF
      containing residues 60-80 is proposed as important for binding to the Trk
      receptor.

PMID- 7517458
TI  - Tyrosine phosphorylation of glycoproteins in the adult and developing rat brain.
AB  - The tyrosine phosphorylation of glycoproteins in the adult and developing rat
      brain was investigated. Immunoblotting with anti-tyr(P) antibodies identified a
      glycoprotein with an apparent Mr of 180,000 (GP180) as the major tyrosine
      phosphorylated protein in the concanavalin A (con A)-binding fraction prepared
      from forebrain homogenates. This glycoprotein had the same electrophoretic
      mobility as the postsynaptic density (PSD)-associated glycoprotein PSD-GP180.
      Tyrosine-phosphorylated GP180 was enriched 24-fold in isolated PSDs relative to
      homogenates. Digestion with endoglycosidase F/N-glycosidase F demonstrated that
      GP180 present in total homogenates and PSD-GP180 present in isolated PSDs
      contained similar amounts of N-linked oligosaccharide suggesting that they are
      the same glycoprotein. The tyrosine phosphorylation of GP180 in homogenates
      varied between brain regions with the highest levels occurring in cortical areas
      and the amygdala and low or undetectable amounts being present in hindbrain
      regions. Incubation of homogenates with adenosine triphosphate (ATP) resulted in
      the tyrosine phosphorylation of GP180 in all regions examined except the
      cerebellum and identified a second con A-binding glycoprotein, GP110, which was
      phosphorylated on tyrosine. GP180 was not phosphorylated on tyrosine following
      the incubation of cerebellar homogenate, synaptic membranes, or PSDs and ATP.
      Tyr(P)-GP180 was not detected prior to the onset of synaptogenesis, increased in
      parallel with the formation of synapses during the first 4 weeks of postnatal
      development of the frontal cortex and hippocampus, and then decreased 50-60% to
      adult levels. The results suggest that GP180 corresponds to the PSD glycoprotein
      PSD-GP180 and are consistent with a role for this glycoprotein in synaptic
      development and signal transduction at the synapse.

PMID- 7517460
TI  - Visual hallucinations in patients with choroidal neovascularization.

PMID- 7517459
TI  - Phenotypic and cytogenetic characterization of human bladder urothelia expanded
      in vitro.
AB  - A simple method for the harvest of bladder cell types from surgical specimens was
      used to generate strains of normal human urothelial cells that could be
      reproducibly cultivated, passaged and extensively expanded in serum-free medium.
      Immunostaining of the bladder epithelial cells with broadly reacting anti
      cytokeratin antibodies and with an anti-cytokeratin antibody specific to
      cytokeratin 7, a transitional cell marker, indicated that they expressed a stable
      epithelial phenotype with serial passage. Low levels of immunostaining for E
      cadherin and low levels of E-cadherin messenger ribonucleic acid, as determined
      by Northern blot analysis, and strongly positive immunostaining with an anti
      vimentin antibody indicated collectively that the uroepithelial cells express a
      nonbarrier-forming phenotype under these culture conditions. However, when the
      urothelial cells were implanted subcutaneously into athymic mice on biodegradable
      synthetic polymers, they formed multilayered structures, suggesting that they
      retain the capability to differentiate in a living host. The urothelial cells
      proliferated in an epidermal growth factor independent manner and expressed high
      levels of transforming growth factor-alpha and amphiregulin messanger ribonucleic
      acids, suggesting the possibility of autocrine regulation of growth by epidermal
      growth factor-like factors. Cytogenetic analysis indicated that urothelial cells
      cultured for 6 passages possessed a normal chromosomal complement. These results
      demonstrate that primary cultures of autologous human bladder epithelial cells
      can be extensively expanded in vitro and, consequently, might be used in cell
      transplantation strategies for genitourinary reconstruction.

PMID- 7517462
TI  - Days required for 75% suppression of ventricular premature contractions by
      antiarrhythmic agents obtained from continuous in-hospital ECG monitoring.
AB  - To determine the number of days required to obtain 75% suppression of ventricular
      premature contractions (VPCs) by antiarrhythmic agents, which was expressed as
      t1/4, we performed 32 in-hospital continuous all day ECG monitoring trials in
      four groups of 28 symptomatic patients (ages; 54 +/- 20 years-old) with frequent
      VPCs. Nine patients had no organic heart disease (group 1, 11 trials), nine had
      valvular heart disease (group 2, 10 trials), three had dilated cardiomyopathy
      (group 3, 3 trials) and seven had myocardial infarction within two to four weeks
      onset (group 4, 8 trials). All patients were monitored by ECG telemetry with an
      arrhythmia analyzer, which could count hourly and daily VPCs. Class I
      antiarrhythmic agents were given in 18 trials, class II in two trials and class
      I+ class II in 12 trials. Plasma concentrations of the antiarrhythmic agents were
      monitored in 11 trials. In 21 trials, t1/4 could be obtained; ten (91%), six
      (60%), three (100%) and two trials (25%) in the four groups, respectively (p <
      0.05). The value of t1/4 in the four groups was 6 +/- 6, 7 +/- 6, 14 +/- 11 and
      13 +/- 2 days, respectively (mean 8 +/- 7 days; N.S.). Immediate response to the
      initial antiarrhythmic agent administration, expressed as percent VPC count after
      three hours, correlated significantly with t1/4 (r = 0.696, p = 0.0006), but
      ejection fraction, patient's age, control VPC counts or plasma antiarrhythmic
      agent level did not correlate with t1/4. In conclusion, t1/4 is a useful index
      for the evaluation of VPC suppression, revealing wide inter-individual variations
      and can be roughly estimated from the immediate response to the initial
      antiarrhythmic agent administration.

PMID- 7517463
TI  - [Molecular cloning, expression and epitope mapping of nuclear antigen].
AB  - The antinuclear antibody is a major characteristic phenomenon in systemic type of
      autoimmune diseases. There is a good correlation between symptoms or diseases and
      the types of antinuclear antibodies in these patients. Therefore, the study of
      the mechanisms of antinuclear antibody production is thought to be important in
      the elucidation of the pathogenesis of such autoimmune diseases. The conventional
      methods to detect antinuclear antibodies have been useful to date in clinical
      studies. However, these methods are not sufficient for more precise
      investigations. Thus, we have applied the recently developed molecular biology to
      this field. cDNAs which encode nuclear antigens have been cloned and their
      protein products were expressed as recombinant fusion protein in E. coli. By this
      procedure, we could establish simple and reproducible method to detects
      antinuclear antibodies. Furthermore, epitope mapping of nuclear antigens could be
      performed using deletion mutants generated by enzymatic manipulations of the
      cDNAs. These epitope studies are facilitating a more precise understanding of the
      mechanisms of antinuclear antibody production.

PMID- 7517461
TI  - Influence of arotinolol hydrochloride on heart rate spectrum in hypertensive
      subjects.
AB  - Influence of arotinolol hydrochloride and atenolol on the balance between the
      sympathetic and parasympathetic nervous systems was evaluated in 8 hypertensive
      subjects by spectral analysis of heart rate (HR) and systemic blood pressure
      (BP). Before and after administration of either arotinolol (n = 7) or atenolol (n
      = 7) for 2 weeks, BP was continuously and non-invasively monitored by a finger
      cuff manometry (Finapres). A time series of instantaneous HR was constructed from
      the BP signal. A time series of mean BP was also constructed. Spectral analysis
      was performed by the use of an autoregressive algorithm on these time series
      (approximately 180 sec). Each spectrum was subdivided into low-(0.05-0.15 Hz, LF)
      and high-frequency (0.15-0.4 Hz, HF) components, and each component was divided
      by the sum of the two for normalization. As a measure of the balance between the
      sympathetic and parasympathetic nervous systems, the ratio of LF to HF (LF/HF)
      was evaluated. Arotinolol increased fractional HF in the HR spectrum from 0.45 +/
      0.12 to 0.73 +/- 0.08 (p < 0.01) and decreased fractional LF from 0.55 +/- 0.12
      to 0.27 +/- 0.08 (p < 0.01); consequently, it decreased LF/HF from 1.4 +/- 0.5 to
      0.4 +/- 0.2 (p < 0.01). Atenolol had similar effects on these parameters. Neither
      of these beta-adrenergic blockades produced a discernible decrease in LF/HF in
      the BP spectrum. In conclusion, these beta-adrenergic blockades decreased LF/HF
      in the HR spectrum in hypertensive subjects, which suggests that they improved
      the balance between the sympathetic and parasympathetic nervous systems.

PMID- 7517464
TI  - [Time-resolved-fluoroimmunoassay for the determination of prostate-specific
      antigen in capillary-blood spotted on filter paper and its clinical significance
      in prostate cancer patients].
AB  - Prostate-specific-antigen (PSA) has recently become widely recognized as an
      important tumor marker for prostate cancer. For relieving the examinee from pain
      and saving the time in blood collection, we developed a new method, based on time
      resolved fluoroimmunoassay (TR-FIA), using a dried disc paper to collect
      capillary-blood. The standard curve ranged from 1.0 to 300 ng/ml, the intraassay
      (CV% was 4.09 to 6.36 (n = 10), while the interassay CV% was 3.45 to 8.87 (n = 2,
      k = 7). The diluted linearity and analytical recovery (91.5 to 98.2%) seemed to
      be satisfactory for routine use. All the samples from 30 healthy male adults had
      non-detectable serum PSA less than 1.0 ng/ml. When the cut-off value was set at
      3.4 ng/ml (MEAN + SD of BPH), the positive rate in prostate cancer cases was
      85.7% (12/14), in BPH cases was 20.0% (2/10) and in other benign urological
      disease was 0.0% (0/20). The clinical sensitivity was 85.7%, the specificity
      93.3% and the efficacy 90.9%, accordingly. In conclusion, the newly developed TR
      FIA method using dried disc paper to collect capillary-blood was quantitatively
      suitable as a routine test for prostate cancer, because of its simplicity in
      blood collection and less invasiveness to the examinee.

PMID- 7517465
TI  - [VEPA and ML-Y1 regimen for elderly non-Hodgkin's lymphoma].
AB  - A total of 32 previously untreated patients aged 65 years or older with non
      Hodgkin's lymphoma (NHL) were treated with VEPA (vincristine, cyclophosphamide,
      prednisolone and doxorubicin) or ML-Y1 (doxorubicin, cyclophosphamide,
      vincristine, methotrexate, bleomycin, procarbazizin and prednisolone). The median
      age of the patients was 70 years (range 65-77), 19 males and 13 females. The
      outcome of 16 patients with VEPA and 16 patients with ML-Y1 was retrospectively
      evaluated. There were no significant differences in response or survival between
      VEPA and ML-Y1, complete remission rates were 37.5% vs. 31.3% and duration of 50%
      survival were 20 months and 13 months, respectively. Major side effects of both
      regimens were myelosuppression, hair loss, nausea, vomiting and peripheral
      neuropathy. There was no increased toxicity in ML-Y1 but this regimen seemed like
      VEPA, to be insufficient for NHL in elderly patients. A new intensive regimen
      should be designed to treat NHL in the elderly patients.

PMID- 7517466
TI  - Neurogenic "off" contractions are mediated by NK2-receptors in the circular
      muscle of guinea pig ileum.
AB  - In guinea pig ileal circular muscle, electrical stimulations by a train of 10-100
      pulses (0.05-msec duration, 10 Hz) produced tetrodotoxin-sensitive "off"
      contractions that were initiated upon the termination of stimulations. Atropine
      at 10(-6) M did not inhibit the "off" contractions. FK224 at 10(-5) M, a dual
      antagonist for NK1- and NK2-receptors, but not 10(-7) M CP-96,345, an antagonist
      for NK1-receptors, almost abolished the "off" contractions in the presence of
      atropine. These results suggest that the neurogenic "off" contraction was
      mediated mainly by NK2-receptors in the circular muscle of guinea pig ileum.

PMID- 7517467
TI  - Calphostin C, a potent and specific inhibitor of protein kinase C, reduces
      phorbol ester-induced but not primary Ca(2+)-induced catecholamine secretion from
      digitonin-permeabilized bovine adrenal medullary cells.

PMID- 7517468
TI  - [Diagnosis of prostate cancer by means of the ratio of prostate specific
      antigen/gamma-seminoprotein (P/S ratio)].
AB  - Prostate specific antigen (PSA) and gamma-seminoprotein (gamma-Sm) are revealed
      to be the same protein. However, the serum concentrations of PSA and gamma-Sm in
      the same samples are frequently different. We previously measured a ratio of
      serum PSA concentration and gamma-Sm concentration (P/S ratio), and evaluated its
      usefulness for diagnosis of prostate cancers. In this paper, we tried to
      determine the cutoff value which brings better efficiency and diagnose prostate
      cancer by means of P/S Ratio. Between April 1988 and September 1992, 221 men
      underwent prostatic biopsy and/or TUR-P, and were diagnosed pathologically. Of
      221 patients, 130 were diagnosed as BPH, prostatis or normal prostate (no cancer;
      NC) and 91 were diagnosed as prostate cancer (CaP). 1) The mean +/- SD of P/S
      ratio in 130 patients with NC was 0.919 +/- 0.563. While, the mean +/- SDs of P/S
      ratio were 12.447 +/- 44.353 in 91 patients with CaP and 2.052 +/- 0.751 in 39
      Cap patients with serum PSA level of < or = 10 ng/ml. The mean P/S Ratios in CaP
      patients with serum PSA of < or = 10 ng/ml as well as in all CaP patients were
      significantly higher than those in NC patients (p < 0.0001). 2) When the cutoff
      value of P/S Ratio was determined to be 1.45, the highest efficiency (=
      sensitivity x specificity divided by 100), 83.4, was obtained. The sensitivity
      and specificity were 91.2% and 91.5%, respectively as a cutoff value of
      1.45.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517469
TI  - From efficacy to value.

PMID- 7517470
TI  - Arterial Diseases: A New Socioeconomic Approach. Proceedings of a symposium.
      Paris, France, May 14, 1993.

PMID- 7517471
TI  - The introduction of economic criteria into the management of arterial disease: an
      illustration with regard to the socioeconomic consequences of peripheral
      occlusive arterial disease of the lower limbs.
AB  - A survey of studies was used to investigate the economic repercussions of
      arterial disease; these repercussions included the cost of the disease and its
      management, and cost/efficacy, cost/utility, and cost/benefit studies of
      preventive, diagnostic, and therapeutic strategies. The study presented is an
      evaluation of the socio-economic consequences of peripheral occlusive arterial
      disease of the lower limbs (POADLL). The cost of health care was measured by
      means of a prospective 6-month study of 85 patients recruited in 6 centers. The
      average cost over the 6-month period was 15,735 FF (1991 francs) ($2,760 U.S.).
      The 85 patients were classified by age, sex, risk factors, concomitant disease,
      and how the illness was managed, notably in terms of hospitalization and vascular
      surgery. The four-group classification was used to calculate an annual management
      cost for POADLL, which ranged from 9,500 FF ($1,667 U.S.) for a stage II patient
      (mean age, 66 years) with no major risk factors and not presenting any
      complication requiring admission to hospital, to 35,000 FF ($6,140 U.S.) for
      patients (mean age, 62 years) who presented major risk factors and who required
      vascular surgery during the year.

PMID- 7517472
TI  - Treatment costs of peripheral arterial occlusive disease in Germany: a comparison
      of costs and efficacy.
AB  - Significant increases in the costs of the health system in all Western countries
      indicate the importance of both economic and efficacy studies in evaluating the
      various treatments for peripheral arterial occlusive disease (PAOD). On the basis
      of this background, an attempt was made to compare the efficacy and the costs of
      different treatment regimens for PAOD using data from the literature. In severe
      PAOD, the therapeutic approaches are supplementary methods that must be applied
      according to the patient's situation; the treatment cannot be chosen on the basis
      of its costs. In patients with claudication, different treatment alternatives
      such as physical exercise, oral or intravenous medical treatment, and
      percutaneous transluminal angioplasty (PTA) exist, and cost-efficacy comparisons
      can be made among these. Oral treatment with vasoactive compounds results in
      efficacy costs ranging from DM 37.31 ($22.61 U.S.) to DM 146.16 ($88.58 U.S.) per
      patient for a drug-induced 10% increase of pain-free walking distance (PFWD)
      using the cheapest therapeutic alternative. Long-term physical exercise (twice
      for 2 h/week for 24 months) leads to efficacy costs of DM 189.09 ($114.60 U.S.)
      per patient for a 10% increase of PFWD. Intensive therapeutic regimens using
      intravenous infusions produce efficacy costs of DM 116.61 ($98.27 U.S.) to DM
      2,529.81 ($1,533.22 U.S.) per patient, but result in an average improvement in
      PFWD of 21% to 62% within 2 to 4 weeks. PTA with a cost of DM 6,000 ($3,636.40
      U.S.) per intervention is the most expensive method of treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7517474
TI  - Quality of life: is it a practical tool in patients with vascular disease?
AB  - With increasing pressure on resources, health care managers are interested in
      evaluating both drug and surgical treatments. A single measure of the quality of
      life of patients may be a useful tool in such an evaluation. We have assessed two
      methods of measuring quality of life in this preliminary study and have found
      them to be useful and simple to assess in patients undergoing vascular surgery.
      Changes between the preoperative values and postoperative values correlate well
      with the clinical impression.

PMID- 7517473
TI  - Health status and quality of life: which matters to the patient?
AB  - The effect of treatment on the health status of patients suffering from
      claudication of the lower limbs has seldom been studied, and their quality of
      life (QOL) not at all. These terms are distinguished and defined. Studies of both
      are important, but it is believed that QOL is of more interest to the patient, as
      representing the individual's appreciation of and reaction to factors of personal
      importance. The many methods employed can be classified according to (a) their
      emphasis on the individual as against the group and (b) their attention to
      internal as against external variables. Problems met in creating new methods for
      the study of QOL are discussed. These include eliciting features of their
      condition that are of specific importance to patients, and establishing the
      different degrees of importance that individuals attach to these. The new
      instrument must be phrased in an acceptable, reliable, and valid form for
      subsequent use. Its validity is most convincingly demonstrated by the ability to
      discriminate between patients with different degrees of disease severity or those
      who have been differently treated, as in a clinical trial. Comparative advantages
      of general and specific methods of inquiry, results expressed as profiles or
      single indicators, and the influence of contextual factors (bias due to timing,
      the effect of the investigator-subject relationship, etc.) are also discussed.

PMID- 7517475
TI  - Serotonin, 5-HT2 receptors, and their blockade by naftidrofuryl: a targeted
      therapy of vascular diseases.
AB  - The importance and the various effects of serotonin (5-HT) in cardiovascular
      diseases are reviewed, with particular emphasis on the involvement of 5-HT2
      receptors as mediators of the biological responses of vessels and blood platelets
      to 5-HT. The importance of 5-HT in peripheral and cerebral ischemia is shown by
      the key role it plays in inducing vasoconstriction, platelet aggregation,
      vascular permeability, and cell proliferation. Of particular importance is the 5
      HT-selective hypersensitivity developing in vessels/platelets shortly after acute
      ischemia or early in the development of chronic vascular diseases. The mechanisms
      of action of naftidrofuryl are described, showing that this drug offers a
      particularly interesting profile of having both metabolic and vascular effects.
      Naftidrofuryl improves glucose aerobic metabolism by an action on
      succinodehydrogenase and improves the blood supply and the ischemic damage of the
      vessel wall by blocking specifically 5-HT2 receptors. The latter property permits
      an inhibition of the deleterious, multiple effects of 5-HT at sites of vascular
      injury, without influencing the general circulatory bed. Therefore, naftidrofuryl
      appears to be an anticonstrictor and not, as previously thought, a vasodilator.
      As a consequence, naftidrofuryl has a targeted impact without vasodilator-linked
      side effects such as hypotension or the steal phenomenon.

PMID- 7517476
TI  - Economic evaluation of drugs in peripheral vascular disease and stroke.
AB  - Increased pressures on health-care budgets mean that governments require good
      value for money from the resources devoted to health care. In many countries,
      measures have been introduced to increase efficiency or to contain health-care
      costs. These include price controls, limitations on reimbursement of health
      technologies, budgetary reform in health-care institutions, and the encouragement
      of competition. Given this changing environment, it is important that drugs and
      other health technologies be shown to give good value for money. The methods of
      economic evaluation, such as cost-benefit and cost-effectiveness analysis, can be
      used to assess the value of drugs and other health technologies. They have been
      widely applied. The economic evaluation of drugs in peripheral vascular disease
      and stroke would compare the cost of adding the drug with its benefits. These
      would include improvements in length and quality of life and the savings in
      treating vascular events that may be postponed, or lessened in intensity, by
      effective drug therapy. One study, following a clinical trial of naftidrofuryl in
      stroke, suggested that there would be significant reductions in costs through
      reductions in hospital stay if recovery was aided. Further research and a large
      multicenter trial are under way to confirm these findings. In peripheral artery
      disease there are no economic data collected alongside clinical trials. It is
      known, however, that the costs of leg ischemia can be significant. A study in the
      U.K. found that arterial construction would cost around pounds 7,750 per person
      (1989 prices) and amputation around pounds 11,000 per person.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7517477
TI  - An evaluation of patients with severe intermittent claudication and the effect of
      treatment with naftidrofuryl.
AB  - A randomized placebo-controlled study was undertaken in 188 patients with severe
      intermittent claudication attending two vascular clinics in Manchester and
      Liverpool. After a 4-week run-in period, patients received active or placebo
      treatment for 24 weeks. Patients were assessed on a treadmill prior to the 4-week
      run-in period, at randomization, and at 8, 16, and 24 weeks. Outcome was measured
      in terms of change in pain-free walking distance, maximum walking distance, and
      pressure indices. In this severe claudication population, in which the patients
      presented with a mean pain-free walking distance of 60 m, an intention-to-treat
      analysis demonstrated that the outcome in the naftidrofuryl-treated group was
      significantly better than in the group receiving placebo (p = 0.045).
      Additionally, 7% of patients in the naftidrofuryl group deteriorated compared
      with 22% in the placebo group (p = 0.005). Of the various risk factors that were
      recorded during the study--smoking habits, the presence of hypertension,
      diabetes, obesity, and duration of illness--only duration of illness had a
      significant influence on outcome. Maximum walking distances alone were not
      significantly influenced by treatment, but the use of a combined index of pain
      free walking distance, maximum walking distance, and pressure indices to record
      success or failure confirmed a significant treatment effect (p = 0.047). A higher
      incidence of minor gastrointestinal symptoms was recorded in the naftidrofuryl
      treated group. Treatment with naftidrofuryl was shown to prevent or slow the
      deterioration observed in a group of patients with severe claudication over a 24
      week period.

PMID- 7517478
TI  - Naftidrofuryl in intermittent claudication: a retrospective analysis.
AB  - A retrospective analysis was performed on all five published clinical trials in
      which naftidrofuryl was given at a dosage of 600 mg daily. Two studies were
      undertaken in France, two in Germany, and one in Great Britain. Data for the
      analysis, which included the presence of risk factors, treadmill walking
      distances, and cardiovascular critical events that occurred during the course of
      the study, were generated from the patients' original study file. Included in the
      analysis were 888 patients, 447 receiving naftidrofuryl and 441 receiving
      placebo. Although there were significant differences between the studies with
      regard to certain variables, distribution was comparable between the treatment
      groups justifying an analysis on the pooled sample. An intention-to-treat
      analysis based on a success/failure outcome was in favor of active treatment (p =
      0.003) as was an analysis of change in pain-free walking distance (PFWD) (p <
      0.002). None of the risk factors had any significant influence on change in PFWD.
      A further analysis indicated that there were significantly fewer cardiovascular
      critical events in the naftidrofuryl group than in the placebo group (p = 0.029).
      Because the incidence of cardiovascular critical events was lower in those
      patients who showed the greatest improvement in PFWD, and as surgical
      intervention was the most frequently encountered critical event, it is possible
      that treatment with naftidrofuryl may lead to a reduction or postponement of
      surgery. Such a finding would have implications for health-care resources.

PMID- 7517479
TI  - Epidemiology of peripheral arterial disease.
AB  - With the aging of the population of most developing nations, arteriosclerosis is
      becoming a major health problem. Although much research has concentrated on the
      coronary and cerebral forms of the disease, peripheral arterial disease has
      received little attention from epidemiologists. The "Rose questionnaire" has been
      used extensively to diagnose intermittent claudication; however, the current
      method of choice for the diagnosis of peripheral arterial disease in
      epidemiologic studies is the ankle brachial pressure index. The prevalence of
      intermittent claudication, diagnosed by the Rose questionnaire, differs according
      to age, sex, and geographical location varying between 0.4 and 14.4%; similar
      variability (from 4.2 to 35%) is seen for disease diagnosed by the ankle brachial
      pressure index. The major risk factor for peripheral arterial disease is
      cigarette smoking; hypertension and diabetes have been identified as risk factors
      in a number of studies; impaired glucose metabolism, dislipidemia, degree of
      physical activity, and coagulation factors have been identified in some
      populations. The coexistence of cardiocerebrovascular and peripheral vascular
      diseases enhances the risk of early death, which is more than double that in the
      general population: The most frequent cause of death is myocardial infarction.
      More work is required to document the natural history of the disease, the risk
      factors for its progression, its relationship with cardiovascular disease, and
      the effect of intervention strategies.

PMID- 7517480
TI  - Impaired cell-mediated immunity to cytomegalovirus (CMV) in leukemic children
      with prolonged CMV viruria.
AB  - To determine the role of cell-mediated immunity (CMI) to cytomegalovirus (CMV) in
      leukemic children after CMV infection, CMI to CMV antigen was studied using CMV
      specific lymphocyte blastogenic responses (LBR) and interferon (IFN) production.
      Four children, who continuously secreted CMV in urine more than 2 years after
      symptomatic CMV infection (CMV disease) (group 1), showed impaired LBR to CMV
      antigen, though they had normal LBR to phytohemagglutinin (PHA) and concanavalin
      A (Con A). Impairment of LBR either to AD-169 strains or autologous and
      heterologous wild strains was observed. IFN production was not detected in three
      of four children. Six leukemic children, who had no viruria after cessation of
      CMV disease (group 2), showed good responses to CMV antigens. IFN was detected in
      all six children in group 2. Eight leukemic children, who were seropositive to
      CMV at the onset of leukemia (group 3), showed good responses to CMV antigens and
      IFN production. These results suggest that impaired cell-mediated immunity to CMV
      antigen might contribute to prolonged excretion of CMV in urine in leukemic
      children.

PMID- 7517481
TI  - Modulation and intracellular transport of CD20 and CD21 antigens induced by B1
      and B2 monoclonal antibodies in RAJI and JOK-1 cells--an immunofluorescence and
      immunoelectron microscopy study.
AB  - By fluorescence microscopy (FM), flow cytometry (FCM) and immunoelectron
      microscopy (IEM) we have shown that B1 and B2 monoclonal antibodies (MoAbs) were
      able to induce modulation of CD20 and CD21 in RAJI and JOK-1 cell lines.
      Redistribution and internalization of both antigens (Ags) after binding with
      MoAbs was readily demonstrated by FM, and by IEM CD20 and CD21 were found to be
      processed by the pathway of receptor-mediated endocytosis. The rate of
      intracellular transport varied: CD21 > CD20 and RAJI > JOK-1. Approximately 65
      and 55% of CD20 and 60 and 45% of CD21 were cleared from the surface of RAJI and
      JOK-1 cells, respectively (FCM and IEM). These values, however, clearly exceeded
      those corresponding to internalization (11, 9, 24 and 16%) indicating shedding of
      Ag-MoAb complexes. No evidence of recycling was found. The present data support
      the hypothesis that the kinetics of modulation vary from one Ag to another and
      probably also reflect the stage of differentiation of the malignant B-cells. The
      results are discussed in the context of the possible usefulness of B1 and B2
      MoAbs in the therapy of B-cell malignancies.

PMID- 7517482
TI  - Suicide, carbon dioxide, and suffocation.

PMID- 7517484
TI  - Intraepithelial lymphocyte subpopulations and dendritic accessory cells in normal
      and hypertrophic adenoids.
AB  - The adenoids have been studied by immunocytochemistry and electron microscopy in
      children with and without adenoidal enlargement. Compared with normal adenoids,
      the enlarged ones showed a marked increase in the number of intraepithelial gamma
      delta TCR+ lymphocytes and a slight increase in the number of intraepithelial
      CD8+ lymphocytes. This was accompanied by large amounts of dendritic human
      lymphocyte antigen (D related) (HLA-DR+) S-100+ accessory cells in the lymphoid
      tissue underlying the epithelium. By electron microscopy, dead epithelial cells
      apposed to intraepithelial lymphocytes, and clefts of the epithelial lamina,
      could be seen frequently in the enlarged adenoids, whereas, in the normal ones,
      they could not. Based on these findings, the hypothesis is drawn that imbalance
      of the system of the intraepithelial cytotoxic lymphocytes may lead to increased
      killing of epithelial cells and uncontrolled penetration of exogenous agents, and
      hence be involved in the pathogenesis of adenoidal hypertrophy.

PMID- 7517485
TI  - Cloning and characterization of the RNase P RNA genes from two porcine
      mycoplasmas.
AB  - We report the cloning of the RNase P RNA genes from the primary aetiological
      agent of porcine pneumonia, Mycoplasma hyopneumoniae, and the closely related
      commensal, Mycoplasma flocculare. The monocistronic genes each have promoters
      with AT-rich -35 regions and Rho-independent-like transcription terminators which
      are retained in the RNase P RNA. Both of these RNase P RNA variants are shown to
      be catalytically active in vitro in spite of a low overall GC content (30%). Our
      results suggest a new example of a stable mini-helix in the conserved core of the
      mycoplasmal RNase P RNAs. Deletion of the corresponding structural element in
      Escherichia coli RNase P RNA (M1 RNA) generated an RNase P RNA with an impaired
      substrate interaction. Displacement of this structural element with the
      mycoplasmal mini-helix resulted in an enzyme with a phenotype similar to that of
      wild-type M1 RNA. In addition, this structural element is important for lead ion
      induced cleavage at specific sites in M1 RNA.

PMID- 7517486
TI  - Coupling between mRNA synthesis and mRNA stability in Escherichia coli.
AB  - Transiently stable products derived from the endonuclease cleavage of transcripts
      from the secEnusG and rplKAJLrpoBC operons have been identified. Cleavage sites
      for RNase III occur in the leader of the secEnusG transcript and in the L12-beta
      intercistronic space of the rplKAJLrpoBC transcript. A single RNase E cleavage
      site was located in the L1-L10 intergenic space. Inactivation of RNase III and
      RNase E results respectively in a one- to twofold and a greater than 10-fold
      stabilization of five mRNA sequences from within the secE, nusG, L11-L1, L10 and
      beta encoding cistrons. The relative amounts of each of these five mRNA sequences
      were found to be nearly constant when measured either in the presence or absence
      of cleavage by RNase III or RNase E. This clearly implies that any increases in
      the stability of these mRNA sequences resulting from the inactivation of
      processing by RNase III or RNAase E are counterbalanced by changes in the mRNA
      synthesis rates. The mechanism that links mRNA synthesis to mRNA decay is not
      known.

PMID- 7517487
TI  - Interaction of the Chlamydia trachomatis histone H1-like protein (Hc1) with DNA
      and RNA causes repression of transcription and translation in vitro.
AB  - The 18 kDa histone H1-like protein from Chlamydia trachomatis (Hc1) is a DNA
      binding protein thought to be involved in condensation of the chlamydial
      chromosome during late stages in the chlamydial life cycle. Expression of Hc1 in
      Escherichia coli results in an overall relaxation of DNA and severely affects
      DNA, RNA and protein synthesis. We have analysed the interaction of Hc1 with
      single-stranded DNA and RNA by Southwestern and Northwestern blotting.
      Furthermore, we show that purified, recombinant Hc1 dramatically affects
      transcription and translation in vitro at physiologically relevant
      concentrations. These results were found to coincide with the formation of
      condensed Hc1-DNA and Hc1-RNA complexes as revealed by agarose gel
      electrophoresis and electron microscopy. The implications of these results for
      possible functions of Hc1 in vivo are discussed.

PMID- 7517483
TI  - Tumor necrosis factor-alpha production in human head and neck squamous cell
      carcinoma.
AB  - Recent studies suggest that tumor necrosis factor-alpha (TNF-alpha), a
      pleiotropic cytokine, is responsible for some of the systemic and local effects,
      including tumor-associated cachexia and neoplastic bone destruction, seen in
      patients with cancer. This study was undertaken to determine if TNF-alpha is
      produced by human squamous cell carcinoma of the head and neck, and, if so, to
      determine its source and cellular distribution. Tumor specimens from nine
      patients with squamous cell carcinoma of the head and neck region were
      immunohistochemically examined for the presence of TNF-alpha. TNF-alpha was
      localized with antibody to human TNF-alpha by the immunoperoxidase method to the
      tumor and vessel endothelial cells in all nine specimens. By Western blot
      analysis, two protein bands recognized by anti-human TNF-alpha antibody in the
      soluble proteins of the tumor specimens were identified. These proteins--25 KD
      and 17 KD--represent the precursor and mature forms of TNF-alpha. To verify
      squamous cell carcinoma production of TNF-alpha, a cell culture of human head and
      neck squamous carcinoma was examined. The 25 KD immunoreactive protein, the TNF
      alpha precursor, was found in extracts from this culture by Western blot
      analysis. These findings suggest that tumor cells are able to produce TNF-alpha;
      this production may explain some of the systemic and local effects seen in
      patients with squamous cell carcinoma of the head and neck.

PMID- 7517488
TI  - Thrombin-induced increase of F-actin in human umbilical vein endothelial cells.
AB  - The actin cytoskeleton of the endothelium plays a key role in the maintenance of
      an endothelial permeability barrier. Inflammatory agonists, such as thrombin,
      cause an increase in vascular permeability associated with changes in the actin
      filament system. However, the full nature and extent of agonist-induced changes
      to endothelial actin have not been documented. We have studied the actin
      cytoskeleton in human umbilical vein endothelial cells (HUVEC) growing on tissue
      culture plastic coverslips or 0.4-micron pore-size polycarbonate membranes. We
      found: (1) Thrombin (0.3 U/ml) induced a rapid (within 5 min) increase in the
      number of microfilaments in HUVEC. (2) Using a quantitative assay for cellular
      filamentous actin (F-actin), thrombin induced a 1.7-fold increase in HUVEC F
      actin within 1 min which persisted for at least 30 min. (3) Blockage of the
      thrombin-induced intracellular calcium ion ([Ca2+)i) signal did not block the
      thrombin-induced increase in F-actin, and calcium ionophores did not cause an
      increase in F-actin. (4) Protein kinase C inhibitors (calphostin C and
      staurosporine both at 100 nM) partially blocked the actin increase. Higher doses
      of staurosporine (500 nM) resulted in complete blockage of the thrombin-induced
      increase in F-actin. (5) Treatment with phorbol ester (100 nM PMA) or mezerein
      (100 nM) did not produce significant changes in F-actin content. These results
      suggest that an increase in [Ca2+]i is not necessary for the thrombin-induced
      increase in endothelial F-actin and, further, that the effect is mediated by
      protein kinases not yet identified.

PMID- 7517490
TI  - Electrophysiological characteristics of cultured human umbilical vein endothelial
      cells.
AB  - Electrophysiological characteristics of cultured human umbilical vein endothelial
      cells (HUVEC) were determined using the patch-clamp technique in the whole cell
      configuration. In isolated cells, membrane potential, capacitance, and input
      resistance were (Mean +/- SD) - 16.3 +/- 12.7 mV, 53.9 +/- 26 pF, and 2.3 +/- 1.3
      G omega, respectively (N = 26); and in confluent cells - 23.6 +/- 5.5 mV, 127 +/-
      59 pF, and 0.254 +/- 0.077 G omega, respectively (N = 6). The almost 10 times
      higher input resistance, and smaller capacitance of isolated versus confluent
      cells, indicated that the latter were in electrical communication, presumably
      through open gap junctions, which was confirmed by intercellular diffusion of
      Lucifer Yellow. Whole-cell currents of isolated cells were made up of at least
      three components: First, two outward currents, an early transient one with
      activation-inactivation kinetics and a small delayed sustained component with
      6.75 +/- 4.8 and 0.73 +/- 0.089 nS conductance, respectively. Second, an inward
      component which was rectified and had 1.58 +/-1.2 nS conductance. In contrast to
      a reported lack of voltage-gated channels in HUVEC, the above currents were
      voltage dependent. Inhibition of the whole-cell currents by external Ba2,
      internal Cs, and other K+ blockers indicates that the three observed currents are
      carried by K+. This was confirmed by changes of outside K+ concentrations
      shifting the I-V curve intercept in the direction expected for K(+)-selective
      channels. Voltage-gated Ca2+ currents were not apparent in the whole-cell current
      records. HUVEC membrane potential was as low as that of microvascular cells,
      while inward current rectification at normal external K+ was like that in
      arterial endothelial cells. This mixed phenotypic expression and multipotential
      behavior suggests that the electrical features of HUVEC may be primarily
      determined by embryonic origin and the local effect of the microenvironment
      rather than strictly by vessel size.

PMID- 7517489
TI  - Quantitation of angiogenesis and antiangiogenesis in the chick embryo
      chorioallantoic membrane.
AB  - A novel method for quantitating angiogenesis and its inhibition has been
      developed for the chick embryo. The method is based on the vertical growth of new
      capillary blood vessels into a collagen gel through two parallel nylon meshes
      which align the capillaries for counting. Angiogenesis is induced by basic
      fibroblast growth factor contained within the gel and slowly released by aluminum
      sucrose octasulfate (sucralfate) or by tumor cells implanted on the gel. The
      potency of four different angiogenesis inhibitors was compared at concentrations
      of 0.6 to 600 nmole. This technique may facilitate the discovery and development
      of angiogenesis inhibitors for clinical application.

PMID- 7517491
TI  - Involvement of nitric oxide and cyclooxygenase products in photoactivation
      induced microvascular occlusion.
AB  - Photoactivation of intravascular dyes with high doses of light is a technique
      used clinically to treat tumors. This procedure results in arteriolar
      constriction, mast cell degranulation, platelet thrombus formation, and,
      ultimately, microvascular stasis. In vivo microscopy was utilized in the current
      study to examine if the endothelial release of prostaglandins and nitric oxide
      could participate in the microvascular effects of photoactivation. Diameter
      changes and thrombus formation of arterioles and venules of the cremaster muscle
      of male Sprague-Dawley rats were quantitated during continuous light activation
      of intravascular fluorescein isothiocyanate conjugated to bovine serum albumin.
      Vasoconstriction and thrombus development were assessed separately, using the
      relationships between the width of the red blood cell column, the inner wall
      diameter, and the thickness of the plasma layer. Venular photoactivation resulted
      in thrombus growth which reached 30% of the maximum size by 16.8 +/- 3.71 min and
      a subsequent growth rate of 6.2 +/- 1.64 microns/min. In arterioles, 30% thrombus
      growth occurred at 14.0 +/- 2.02 min with a growth rate of 3.0 +/- 0.57
      microns/min. Continuous arteriolar photoactivation led to a vasoconstriction of
      34.4 +/- 6.87% of the initial vessel diameter. Thirty percent of the maximal
      constriction occurred after 10.6 +/- 1.26 min of photoactivation. Constriction
      proceeded at a rate of 3.8 +/- 1.32 microns/min. Topically applied mefenamic acid
      (a cyclooxygenase inhibitor) and Nw-nitro-L-arginine methyl ester (L-NAME, a
      nitric oxide synthase inhibitor) each enhanced both the arteriolar and the
      venular thrombus growth due to photoactivation. Photoactivation-induced
      arteriolar constriction was augmented by L-NAME and inhibited by mefenamic acid.
      These data suggest that the photoactivation of intravascular dyes is accompanied
      both by the release of nitric oxide, which inhibits thrombus development and
      arteriolar constriction, and by the release of cyclooxygenase products, which
      inhibit thrombus growth and induce vasoconstriction. Rats treated with busulfan
      to induce thrombocytopenia exhibited a 90% decrease in circulating platelets. In
      these animals, photoactivation caused significantly delayed thrombus growth in
      arterioles and venules, while arteriolar constriction remained unaltered,
      suggesting that the vasoconstrictor prostanoid is not of platelet origin.

PMID- 7517492
TI  - Angiogenesis induced by mast cell secretion in rat peritoneal connective tissue
      is a process of three phases.
AB  - In the present study methods for morphometric evaluation of angiogenesis in the
      mesenteric window model were developed and used to assess kinetics of
      angiogenesis induced by either ip saline or the mast cell secretagogue 48/80.
      Morphometric variables included vessel density (VD), vessel luminal diameter
      (VLD), vessel luminal surface area (VSA), vessel luminal volume (VLV),
      vascularized area (VA), and number of circumferential vessels (CV). The kinetic
      pattern induced by 48/80 consisted of three phases. The first phase was
      characterized by a pronounced increase of CV, VD, VSA, and VLV and a decrease of
      VLD on Day 9. The second protracted phase (Day 9 to Day 37) was characterized by
      a continuing increase of VA together with remodeling of the vascular network
      (decrease of CV, VD, VSA, VLV and normalization of VLD). In the third phase (Days
      37-65) no further expansion of the vascular network was present. Following saline
      injections ip, the characteristic kinetic pattern was a transient initial
      expansion of the vessel trees with significant increases of CV, VSA, and VLV on
      Day 9, while VD and VLD were unchanged, followed by a continuous regression. The
      results, including a protracted distinguishing second angiogenesis phase after
      48/80 injections, strongly argues against short-lived mediators released from
      mast cells as decisive for the process but rather indicate that other factors,
      possibly related to macrophage infiltration are important.

PMID- 7517494
TI  - Progress toward global eradication of poliomyelitis, 1988-1993.
AB  - In May 1988, the World Health Organization (WHO) adopted a resolution to
      eradicate poliomyelitis by the year 2000. Since then, all six WHO regions have
      made substantial progress toward this goal using three major control strategies:
      1) maintaining high coverage of children with at least three doses of oral
      poliovirus vaccine (OPV3); 2) administering supplementary doses of OPV to all
      young children (generally those aged < 5 years) during National Immunization Days
      (NIDs)* and during door-to-door vaccination campaigns in areas where wild
      poliovirus circulation persists at low levels; and 3) developing sensitive
      systems of epidemiologic and laboratory surveillance (1). This report summarizes
      progress of the global polio eradication initiative from 1988 through 1993.

PMID- 7517493
TI  - [Chronic viral hepatitis and its treatment with interferon].

PMID- 7517496
TI  - Antagonist-mediated down-regulation of 5-hydroxytryptamine type 2 receptor gene
      expression: modulation of transcription.
AB  - Prolonged exposure to an agonist results in a progressive loss of most G protein
      coupled receptors, whereas exposure to an antagonist causes increased receptor
      response. The 5-hydroxytryptamine (5-HT)2 receptor is down-regulated by agonists
      but, paradoxically, antagonists can also elicit a decrease in receptor density.
      Here we show that long term treatment with serotonin or mianserin, an antagonist
      and antidepressant, results in reduced levels of both the 5-HT2 receptor and its
      RNA. Antagonist-induced down-regulation requires the presence of the 5-HT2
      receptor, it occurs at the level of transcription, and it is mediated by a drug
      response sequence in the 5' flanking region of the 5-HT2 receptor gene. The
      effect of mianserin might result, at least in part, from its ability to modulate
      transcription.

PMID- 7517495
TI  - Introduction of purified alpha 2A-adrenergic receptors into uniformly oriented,
      unilamellar, phospholipid vesicles: productive coupling to G proteins but lack of
      receptor-dependent ion transport.
AB  - Introduction of highly purified alpha 2A-adrenergic receptors (alpha 2AAR) into
      lipid vesicles resulted in vesicle preparations that were unilamellar in
      structure, nonleaky to monovalent cations, and uniformly oriented such that the
      cytoplasmic domains of the alpha 2AAR faced the vesicle exterior. In this
      orientation, addition of Gi/G(o) G proteins yielded a 4-5-fold stimulation of
      agonist-dependent guanosine-5'-O-(3-[35S]thio)triphosphate binding to the G
      protein alpha subunit. These nonleaky, uniformly oriented, alpha 2AAR-containing
      vesicle preparations allowed us to explore the hypothesis that the alpha 2AAR
      itself, or in combination with Gi/G(o) proteins, is able to effect ion
      translocation. Measurements of 22Na+ uptake, 22Na+ efflux, and H+ movement
      revealed no detectable agonist-stimulated, receptor-dependent, ion translocation,
      even in the presence of G proteins, suggesting that allosteric regulation of
      alpha 2AAR by cations and amiloride analogs is not an indication that the alpha
      2AAR itself is an ion transporter. Nonetheless, the methodology developed in the
      present studies for preparation of nonleaky vesicles containing receptor and G
      proteins should be well suited for evaluating the stoichiometry and selectivity
      of receptor-G protein interactions and, in particular, G protein specificity in
      mediating receptor-dependent regulation of voltage-gated or receptor-operated ion
      channels.

PMID- 7517497
TI  - Inhibition of phosphoprotein phosphatases blocks metabotropic glutamate receptor
      effects in the rat nucleus tractus solitarii.
AB  - Whole-cell recordings were made from dorsomedial nucleus tractus solitarii
      neurons in thin coronal medullary slices of the rat, at the level of the area
      postrema. Monosynaptic excitatory postsynaptic currents (EPSCs) were evoked in
      the tractus solitarius by electrical stimulation in the presence of D-2-amino-5
      phosphonopentanoic acid (AP5) and bicuculline. Currents were also evoked by
      pressure ejection of (S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate
      (AMPA) in the presence of AP5, bicuculline, and tetrodotoxin or muscimol in the
      presence of 6,7-dinitroquinoxaline-2,3-dione and AP5. The metabotropic glutamate
      receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate [(1S,3R)
      ACPD] reversibly depressed the EPSC and muscimol currents and reversibly
      potentiated AMPA currents. The effects of (1S,3R)-ACPD were blocked in the
      presence of a low concentration of the phosphoprotein phosphatase (PP)1 and PP2A
      inhibitor okadaic acid (OA) but not by a low concentration of the PP inhibitor
      calyculin A. The immunosuppressant agent FK506 failed to block (1S,3R)-ACPD
      effects on AMPA currents. However, (1S,3R)-ACPD applied in the presence of FK506
      produced a reversible potentiation of muscimol currents. We previously
      demonstrated that the cell-permeant cGMP analog 8-Br-cGMP can mimic many of the
      effects of (1S,3R)-ACPD. OA antagonized the effects of 8-Br-cGMP in the present
      investigation. Finally, we previously demonstrated that brief tetanic stimulation
      results in the activation of a presynaptic mGluR autoreceptor and depression of
      subsequently evoked EPSCs. OA similarly blocked tetanus-induced depression of
      EPSCs. These findings suggest that mGluRs on tractus solitarius afferents and
      first-order nucleus tractus solitarii neurons may modulate glutamate release and
      AMPA and gamma-aminobutyric acid type A receptor activity via activation of one
      or more PPs, such as PP2A and/or calcineurin.

PMID- 7517499
TI  - Effects of alcohols and volatile anesthetics on the activation of nicotinic
      acetylcholine receptor channels.
AB  - The n-alcohols butanol through nonanol and the volatile anesthetic ether increase
      the frequency of bursts of nicotinic acetylcholine (ACh) receptor channels
      induced by low concentrations of agonists. For example, 10 mM butanol increases
      the burst frequency induced by 0.2 microM ACh (a full agonist) and 1 microM
      decamethonium (a partial agonist) by 1.6-fold and 2.7-fold, respectively. An
      increase in burst frequency could arise from effects of the drug on agonist
      binding, channel gating, or desensitization. To distinguish among these
      alternatives, we measured the current response to rapid application of saturating
      concentrations of agonists. We found that 10 mM butanol increases the peak
      current induced by 100 microM decamethonium by 2-fold. In addition, 20 mM butanol
      and 3 mM pentanol both decrease the onset time of the current response to 10 mM
      ACh by about 40%. In contrast, ether does not increase the current response to
      100 microM decamethonium and does not significantly change the onset time for 10
      mM ACh. Neither ether nor butanol changes the degree of steady state
      desensitization induced by 0.2 microM ACh. We conclude that butanol and pentanol
      increase burst frequency by increasing the channel opening rate, whereas ether
      does so by increasing the agonist binding affinity of the ACh receptor.

PMID- 7517498
TI  - Pharmacological characterization of five cloned voltage-gated K+ channels, types
      Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines.
AB  - We have analyzed the biophysical and pharmacological properties of five cloned K+
      (Kv) channels (Kv1.1, Kv1.2, Kv1.3, Kv1.5, and Kv3.1) stably expressed in
      mammalian cell lines. Kv1.1 is biophysically similar to a K+ channel in C6 glioma
      cells and astrocytes, Kv1.3 and Kv3.1 have electrophysiological properties
      identical to those of the types n and l K+ channels in T cells, respectively, and
      Kv1.5 closely resembles a rapidly activating delayed rectifier in the heart. Each
      of these native channels may be formed from the homomultimeric association of the
      corresponding Kv subunits, and pharmacological compounds that selectively
      modulate them may be useful for the treatment of neurological, immune, and
      cardiac disorders. The cell lines described in this report could be used to
      identify such drugs and we have therefore embarked on a pharmacological
      characterization of the five cloned channels. The compounds tested in this study
      include 4-aminopyridine, capsaicin, charybdotoxin, cromakalim, dendrotoxin,
      diltiazem, D-sotalol, flecainide, kaliotoxin, mast cell degranulating peptide,
      nifedipine, noxiustoxin, resiniferatoxin, and tetraethylammonium.

PMID- 7517500
TI  - Cinnamaldehyde-induced micronuclei in rodent liver.
AB  - Cinnamaldehyde, a widely used flavoring agent, has so far been subjected to a
      limited range of genotoxicity tests, mainly carried out in vitro, which produced
      contradictory results. Therefore we have examined cinnamaldehyde using additional
      in vivo genotoxicity end-points. In Sprague-Dawley rats, a single oral dose equal
      to 1/2 LD50 did not induce DNA fragmentation in liver and gastric mucosa as
      evaluated by the alkaline elution technique, increased the frequency of
      micronucleated hepatocytes but not of bone marrow micronucleated polychromatic
      erythrocytes, and gave rise to a significantly higher incidence of total nuclear
      anomalies but not of micronucleated cells in forestomach mucosa. In Swiss mice,
      the equitoxic dose of cinnamaldehyde caused the same clastogenic effect in the
      liver, whilst a negative response was observed in both bone marrow and
      forestomach mucosa. Finally, in rats initiated with N-nitrosodiethylamine the
      administration of 500 mg/kg/day cinnamaldehyde for 14 successive days produced a
      modest but statistically significant increase of the average diameter and area of
      gamma-glutamyltranspeptidase-positive foci that, together with changes observed
      in other parameters, might be considered indicative of a potential promoting
      activity. Taken as a whole, these findings confirm that high doses of
      cinnamaldehyde may induce genetic alterations at the chromosomal level, and
      suggest that the liver is the preferential target of its undesirable effects.

PMID- 7517503
TI  - Induction of genotoxicity by salted deep-fried fish and mutton.
AB  - Salted, sun-dried and deep-fried fish and mutton were screened for their
      mutagenicity by the Ames test, single cell gel electrophoresis assay (SCG),
      chromosomal aberrations (CA), and micronucleus test. Fish and mutton given at 20%
      in the diet to the rats daily for 2 months resulted in cytogenetic damage which
      could not be repaired on withdrawal. However, the temporary damage was reversed
      at a 10% dose upon withdrawal after the same period. The maximum chromatid
      damage, found as breaks and gaps, was in agreement with the increased number of
      strand breaks. Treated rats also showed DNA strand breaks in hepatocytes and
      lymphocytes, more so in hepatocytes. Lime and onion extracts inhibited the
      nitrosation of fish and mutton, and were antitoxic.

PMID- 7517501
TI  - Inhibitory activity of cigarette-smoke condensate on the mutagenicity of
      heterocyclic amines.
AB  - Cigarette-smoke condensate (CSC) is a complex mixture containing over 3800
      identified chemicals including nicotine, water, mutagens, antimutagens,
      cytotoxins and inert chemicals. Although CSC is mutagenic in the Ames test, its
      effect on the activity of other mutagens has not been characterized. Using the
      Ames Salmonella bacterial mutagenesis assay, we found CSC exerts a significant
      inhibitory effect on mutagens requiring bioactivation. Those studied included
      heterocyclic amines (Glu-P-1, Glu-P-2, IQ, MeIQ, Trp-P-1 and Trp-P-2),
      benzo[a]pyrene (B[a]P) and aflatoxin B1. However, CSC had no effect on the
      activity of direct-acting mutagens (2-nitrofluorene, sodium azide, 4-nitro-1,2
      phenylenediamine, 4-nitroquinoline N-oxide and methyl methanesulfonate). With
      indirect-acting mutagens, the reduced number of revertants observed in the
      presence of CSC was not attributable to cytotoxicity. CSC exhibited a potent
      inhibitory effect on the cytochrome P-450 dependent monooxygenases,
      ethoxyresorufin O-deethylase and B[a]P hydroxylase. This suggests inhibition of
      the cytochrome P-450 isozymes as one possible mechanism for the antimutagenicity
      of CSC. Fractionation studies of CSC revealed that the neutral, weakly acidic
      (phenolic) and basic fractions are all effective as antimutagens against Glu-P-1,
      a representative heterocyclic amine. This indicates that several classes of
      chemicals contribute to the inhibitory effect of CSC on the mutagenicity of the
      heterocyclic amines.

PMID- 7517504
TI  - Carboplatin treatment induces dose-dependent increases in the frequency of
      micronuclei in Ehrlich ascites tumor cells.
AB  - The effect of various doses (75-300 mg/kg b.w.) of carboplatin on the induction
      of micronuclei in Ehrlich ascites tumor (EAT) cells was studied. Carboplatin
      treatment resulted in a dose-dependent increase in the frequency of
      micronucleated EAT cells. Carboplatin treatment also decreased the mitotic index.
      The dose-effect curves were linear-quadratic for all the parameters studied. The
      maximal effect of the drug was obtained in all the treatments after 48 h.

PMID- 7517502
TI  - Genotoxicity studies with chloroethane.
AB  - In a recent 2-year inhalation study with F344 rats and B6C3F1 mice conducted as
      part of the U.S. National Toxicology Program (NTP, 1989), chloroethane (ECl) at
      an exposure concentration of 15,000 ppm induced a high incidence of endometrial
      uterine carcinomas only in female mice but not in rats, leading to the conclusion
      of "clear evidence of carcinogenicity" for the mouse. In order to elucidate
      whether a genotoxic effect may be a critical factor for the carcinogenicity of
      ECl in the mouse, we have performed three genotoxicity tests: (1) in vitro HPRT
      test with CHO cells according to a specially developed gas protocol, (2) in
      vivo/in vitro UDS with female B6C3F1 mice at an exposure concentration of 25,000
      ppm (6 h/day, 3 days), (3) in vivo micronucleus assay with male and female B6C3F1
      mice exposed to 25,000 ppm ECl according to the same schedule. In the in vitro
      HPRT test a mutagenic potential of ECl was detected in the presence as well as in
      the absence of S9 mix. In contrast, both in vivo test systems failed to detect
      any indications of genotoxicity of chloroethane at an exposure concentration even
      higher than that of the NTP study. It is suggested that in vivo the genotoxic
      potential of ECl is so low that an assumed genotoxic damage is below the
      detection limit of the test systems used. This leads to the conclusion that
      genotoxicity may not be a key factor in the induction of the uterine carcinomas
      in the B6C3F1 mouse.

PMID- 7517505
TI  - Micronuclei, chromosomal aberrations and aflatoxin-albumin adducts in
      experimental animals after exposure to aflatoxin B1.
AB  - Rats and mice differ markedly in sensitivity to aflatoxin B1 (AFB1)
      hepatocarcinogenicity, the former being sensitive and the latter resistant.
      Animals were treated with single doses of different concentrations of AFB1,
      between 0.01 and 1.0 microgram AFB1/g body weight. The frequency of chromosomal
      aberrations and micronuclei in the bone marrow was measured and compared to the
      level of AFB1 bound covalently to albumin in the peripheral blood. Both
      chromosomal aberrations and micronuclei were significantly increased in treated
      rats compared to the control group at doses above 0.1 microgram/g. In contrast,
      in mice, a slight increase in chromosome aberrations was seen in the highest dose
      group (1.0 microgram/g) but no increase in micronuclei was observed at any of the
      doses. The level of chromosomal aberrations was about 10 times higher in rats
      than in mice at the highest dose of AFB1. AFB1-albumin (AF-alb) adducts did not
      show a strong dose-response increase after treatment in mice, whereas in rats the
      levels increased linearly with dose of AFB1 and there were strong correlations at
      the individual rat level with both chromosomal aberrations (r = 0.92; p < 0.0001)
      and micronucleus frequency (r = 0.86; p < 0.0001). These data suggest that the AF
      alb may reflect the level of genetic alteration resulting from the initial
      binding of this carcinogen to cellular DNA. Therefore, this adduct used as a
      biomarker in studies of human exposure to aflatoxin may provide information not
      only on exposure but also on the risk of genetic alterations consequent to that
      exposure.

PMID- 7517506
TI  - Comparison of the aneugenic activity of diazepam in mouse oocytes and other
      mammalian cells.
AB  - Previous studies have reported that diazepam (DZ) is capable of inducing mitotic
      meiotic arrest and increasing the frequency of aneuploidy in mammalian cells both
      in vitro and in vivo. We now report that DZ failed to induce either meiotic
      arrest or aneuploidy in mouse oocytes. In fact, doses of 0, 50, 100, or 150 mg/kg
      DZ administered at the same time as human chorionic gonadotropin did not induce
      the ovulation of metaphase I oocytes or of hyperploid metaphase II oocytes. A
      reduction in the number of ovulated oocytes was observed in the treated groups
      relative to controls, but this reduction was only significant (p < 0.01) at the
      highest dose. These findings indicate that different results are found among the
      assays used for detecting chemically induced aneuploidy. Determining the factors
      responsible for these differences is an important area for future research.

PMID- 7517507
TI  - Detection of hyperdiploidy and chromosome breakage in interphase human
      lymphocytes following exposure to the benzene metabolite hydroquinone using
      multicolor fluorescence in situ hybridization with DNA probes.
AB  - Increased frequencies of structural and numerical chromosomal aberrations have
      been observed in the lymphocytes of benzene-exposed workers. Similar aberrations
      occurring in bone-marrow cells may contribute to the increased incidence of
      leukemia seen in these populations. Fluorescence in situ hybridization with
      chromosome-specific DNA probes is a relatively new technique which shows promise
      for the identification of aneuploidy-inducing agents. In these studies,
      fluorescence in situ hybridization with several chromosome-specific DNA probes
      was used to investigate the ability of the benzene metabolite hydroquinone to
      induce hyperdiploidy in interphase human lymphocytes. Using a classical satellite
      probe specific for human chromosome 9, a significant dose-related increase in the
      frequency of cells containing 3 or more hybridization regions was observed
      following the in vitro exposure of lymphocytes to hydroquinone at concentrations
      from 75 to 150 microM. At the 100-microM concentration of hydroquinone, the
      frequency of nuclei containing 3 or more hybridization regions was determined
      using probes for chromosomes 1, 7 and 9. Significantly higher frequencies of
      affected nuclei were observed using the chromosome 1 and 9 probes when compared
      to the chromosome 7 probe. To establish whether this difference was due to the
      nonrandom involvement of these chromosomes in hydroquinone-induced hyperdiploidy
      or to chromosomal breakage within the chromosomal region targeted by these
      probes, a multicolor fluorescence in situ hybridization approach was developed
      using probes to two adjacent regions on chromosome 1. Using this tandem-labeling
      approach, the frequency of nuclei with multiple hybridization regions and the
      origin of the regions was determined by scoring slides labeled simultaneously
      with the chromosome 7 alpha satellite probe and the adjacent alpha and classical
      satellite probes for chromosome 1. The results of these studies confirmed that
      hydroquinone exposure resulted in a significant increase in hyperdiploid nuclei,
      but indicated that the different frequency of nuclei containing 3 or more
      hybridization regions observed using the chromosome 1 and 7 probes, was due to
      breakage within the chromosomal region targeted by the chromosome 1 classical
      satellite probe. These results indicate that hydroquinone may contribute
      significantly to the numerical and structural aberrations observed in benzene
      exposed workers. In addition, the multicolor fluorescence in situ hybridization
      approach utilized in these studies promises to be a powerful technique for the
      detection of chromosomal breakage occurring in interphase human cells.

PMID- 7517508
TI  - A reduced level of multiple mutation in a shuttle vector passaged in Sjogren's
      syndrome cells.
AB  - Sjogren's syndrome is a systemic disorder with unknown etiology, displaying many
      signs of autoimmunity. Although the basic mechanism of this disease is unknown, a
      defect in somatic mutagenesis of antibody genes has been suggested. Using a
      shuttle vector plasmid, we here show that the number of vectors with multiple
      base changes in a marker gene was reduced in B cell lines from two patients with
      Sjogren's syndrome (8% in both), as compared with values reported for cell lines
      from normal human donors (16-27%). This finding suggests that a reduction of the
      rate of somatic mutagenesis may influence the development of symptoms in Sjogren
      patients.

PMID- 7517510
TI  - Subtelomeric chromosome instability in Plasmodium falciparum: short telomere-like
      sequence motifs found frequently at healed chromosome breakpoints.
AB  - The stability of chromosome ends of the human malaria parasite P. falciparum was
      analysed using a polymerase chain reaction (PCR) assay that detects potential
      chromosome breaks that have been healed by the addition of telomere repeats. The
      data show that the Pf332 and Pf87 genes located in subtelomeric positions of
      chromosomes 3 and 11, respectively, represent fragile sites. Breakpoints were
      observed in different regions of these genes. In the broken genes, the DNA
      sequences preceding the telomere addition sites generally have complementarity to
      the predicted RNA template of a P. falciparum telomerase ribonucleoprotein enzyme
      complex. We propose a model for the creation of new telomeres in P. falciparum
      adjacent to broken ends containing short telomere-like sequence motifs.

PMID- 7517509
TI  - The presence of KCl in the exposure medium strongly influences the mutagenicity
      of metabolites of polycyclic aromatic hydrocarbons in Escherichia coli.
AB  - Previous studies demonstrated that the ion composition of the exposure medium may
      strongly influence the mutagenicity of many compounds in the liquid preincubation
      modification of the reversion assay with his- Salmonella typhimurium strains.
      Similar influences were now observed in the reversion assay with trp- Escherichia
      coli strain WP2 uvrA. The exposure medium was 8 mM sodium phosphate buffer (pH
      7.4), containing no other ions or 125 mM KCl. Omission of KCl resulted in an
      about 10-fold enhancement of the mutagenic activity of 7-methylbenz[a]anthracene
      5,6-oxide, but in a strong decrease in the mutagenicity of 1-hydroxymethylpyrene
      sulphate, close to the limit of detection. The findings with these two
      representative mutagens are very similar to those previously observed in S.
      typhimurium, suggesting that unobtrusive medium components may exert strong
      influences on the results with many test compounds in various bacterial test
      systems.

PMID- 7517513
TI  - Effects of ethylene on micronucleus formation in the bone marrow of rats and mice
      following four weeks of inhalation exposure.
AB  - Male Fischer 344 rats and male B6C3F1 mice (10/species/group) were exposed to
      ethylene 6 h/day, 5 days/week, for 4 weeks. The ethylene target concentrations
      were 0, 40, 1000, and 3000 ppm. An ethylene oxide (EO) control group for each
      species was exposed under the same conditions at a target concentration of 200
      ppm. Bone marrow was collected approximately 24 h after the final exposure.
      Polychromatic erythrocyte (PCE) to normochromatic erythrocyte (NCE) ratios were
      determined and 2000 PCE/animal were scored for the presence of micronuclei.
      Ethylene did not produce statistically significant, exposure-related increases in
      the frequency of micronucleated PCE (MNPCE) in the bone marrow of either rats or
      mice when compared to air-exposed control animals. As expected, EO exposure
      resulted in significant increases in the frequencies of MNPCE in both species.

PMID- 7517512
TI  - Todralazine influence upon the mutagenicity of some direct- and indirect-acting
      mutagens.
AB  - Todralazine decreased the mutagenic activity of tested direct- and indirect
      acting mutagens. Despite the marked differences between efficient todralazine
      doses (ED50) it was observed that, in the case of tested indirect mutagens as
      well as in some of the direct mutagens, the decrease of mutagenicity by
      todralazine was very strong, exceeding 80% in some cases.

PMID- 7517511
TI  - Effect of scavengers of active oxygen species on cell damage caused in CHO-K1
      cells by phenylhydroquinone, an o-phenylphenol metabolite.
AB  - Phenylhydroquinone (PHQ), a metabolite of o-phenylphenol (OPP), is easily
      autoxidized to phenylbenzoquinone (PBQ) via the semiquinone (phenylsemiquinone,
      PSQ) with concomitant production of superoxide anion radicals (O2-.). We have
      used scavengers of active oxygen species to examine whether or not O2-. produced
      during oxidation of PHQ is related to cell damage in CHO-K1 cells. PHQ at 10
      micrograms/ml (3-h treatment) induced sister-chromatid exchange (SCE),
      endoreduplication (ERD) and cell-cycle delay in CHO-K1 cells. These effects were
      inhibited by catalase (280 U/ml), a scavenger of hydrogen peroxide (H2O2), as
      well as by the reductants, ascorbate (3 mM) and GSH (1 mM). Mannitol (50 mM), a
      scavenger of hydroxyl radical (OH.), was ineffective and superoxide dismutase
      (SOD, 150 U/ml), a scavenger of O2-., or SOD plus catalase rather intensified the
      toxicity as did aminotriazole (20 mM), an inhibitor of catalase. Analyses of
      incubation solutions by HPLC showed that the extent of cell damage is correlated
      with PHQ loss; catalase suppressed PHQ loss, whereas SOD promoted it. The
      correlation was more clearly seen in the time courses of cell death and PHQ loss
      during incubation of PHQ with each of the scavengers of active oxygen species.
      These results show that neither O2-. nor OH. participates in the cell damage, but
      rather H2O2 generated via dismutation of O2-. may participate, probably by
      accelerating the autoxidation of PHQ and thus causing an increase in the
      production of toxic intermediates. In fact, conversion of PHQ to PBQ, a reactive
      product, was demonstrated during incubation with PHQ in phosphate-buffered saline
      by following the changes in UV-visible spectra of PHQ. Inclusion of H2O2 (0.2 or
      1 mM) in the incubation mixture accelerated the PHQ loss. The present results can
      be explained in terms of the autoxidation mechanism of hydroquinone proposed by
      O'Brien (1991). Different from the results in the absence of S9 mix, the cell
      damage induced by 50 micrograms/ml OPP in the presence of S9 mix was not
      influenced by any of the scavengers of active oxygen species used. We conclude
      that PHQ causes cytotoxic and genotoxic effects through its autoxidation, both
      enzymatic and nonenzymatic, and that reactive intermediate(s) such as PSQ and/or
      PBQ may be ultimately responsible for the effects. H2O2 formed during the
      oxidation process participates in the damaging effects caused in the absence of
      S9 mix, probably by accelerating the autoxidation.

PMID- 7517515
TI  - Emerging perspectives on the mechanism of action of gabapentin.
AB  - Significant advances have been made in understanding the molecular and cellular
      mechanisms underlying seizure disorders and the actions of antiepileptic drugs.
      Agents with new mechanisms of action or enhanced activity via known mechanisms
      might provide improved seizure control or more selective therapy for specific
      epilepsies. Gabapentin is a new antiepileptic drug that is structurally similar
      to the neurotransmitter GABA and the endogenous amino acid L-leucine. The
      mechanism of action of gabapentin is not fully understood, but its distinct
      profile of anticonvulsant activity in animal seizure models and its lack of
      activity at many drug binding sites associated with other antiepileptic drugs
      indicate that its mechanism of action is novel.

PMID- 7517514
TI  - A comparative study of four different staining methods for estimation of live
      yeast form cells of Paracoccidioides brasiliensis.
AB  - A comparative study of four different staining methods for estimation of live
      yeast form cells of Paracoccidioides brasiliensis was carried out. The staining
      methods used were fluorescent staining, vital dye exclusion tests with erythrosin
      B and by Janus green and lactophenol cotton blue staining. Colony forming units
      (cfu) of the yeast form of eight P. brasiliensis isolates on brain heart infusion
      agar (BHIA) supplemented with 4% horse serum plus 5% P. brasiliensis cell extract
      (BHIA + HS + EXT) were examined for reliability of staining in determining the
      number of live fungal units in eight different isolates. Cfu on BHIA + HS + EXT
      plates showed an excellent plating efficiency over 96% in all isolates tested.
      The percentage of the live cells indicated by fluorescent staining (FL) or vital
      dye exclusion test with erythrosin B (EB) or Janus green (JG-1) was lower than
      that of cfu. By contrast, the percentage due to modified dye exclusion test with
      Janus green (JG-2) and that due to lactophenol cotton blue staining (LPCB) showed
      a close correration to that of cfu. Our results indicate that the modified dye
      exclusion test with Janus green and lactophenol cotton blue staining are useful
      for estimating cell viability of yeast form cells of P. brasiliensis.

PMID- 7517516
TI  - Examination of tonic nociceptive behavior using a method of substance P-receptor
      desensitization in the dorsal horn.
AB  - Substance P (SP) has been suggested as a neuromediator of nociception in the
      dorsal horn. Following a single injection of SP onto the rat spinal cord,
      nociceptive reflexes are facilitated. Following successive administration of a
      high dose of SP, these responses are attenuated. We have administered multiple
      injections of SP onto the rat spinal cord in order to produce desensitization to
      the SP response. With this procedure, we have observed that phasic behaviors
      (short-term reflex) are attenuated for up to 150 min and are associated with a
      reduction in the number and affinity of SP-binding sites in the dorsal horn. This
      study was performed to examine the effect of SP-receptor desensitization in two
      well-established models of tonic (prolonged) nociception: the formalin test and
      the monosodium urate (MSU) test. Repeated intrathecal administration of SP (15
      micrograms) reduced the first phase but did not alter the second phase of
      formalin-induced pain-related behavior. Similarly, repeated administration of SP
      did not alter MSU-induced pain-related behavior. In both tests, an analgesic dose
      of morphine administered in combination with SP did reduce the nociceptive
      behavior. These data show that alteration of SP-receptor activity in the dorsal
      horn does not alter responses to two longer acting agents considered to be
      nociceptive. These results suggest that SP in the dorsal horn does not directly
      mediate tonic nociception but rather may be involved in the expression of phasic
      pain-related behavior.

PMID- 7517517
TI  - Analysis of the high molecular weight rhoptry complex of Plasmodium falciparum
      using monoclonal antibodies.
AB  - Twenty-one monoclonal antibodies, obtained after immunization of mice with
      erythrocytic stages of Plasmodium falciparum, produced a double dot image in IFA.
      Immunoelectronmicroscopy indicated that the mAbs reacted with the rhoptries.
      Rhoptries are pear-shaped apical organelles, believed to be involved in invasion
      of the host cell by the parasite. The mAbs all immunoprecipitated the high
      molecular weight antigen complex. Some mAbs recognized on immunoblots only 1
      protein of this complex, whereas others reacted with RhopH1 and RhopH3, or RhopH2
      and RhopH3 or with the 3 proteins. An additional antigen of 52 kDa was also
      recognized by some of the mAbs. The epitopes defined by the mAbs were present in
      most of the 40 P. falciparum strains or isolates studied by IFA. Interestingly,
      the mAbs also reacted with high titres on P. vivax and P. ovale, but produced
      images that did not indicate an apical location. The mAbs failed to react on the
      non-human malaria parasites studied, P. cynomolgi and P. inui. On P. berghei or
      P. chabaudi parasites, only 5 mAbs gave a positive reaction, labelling a large
      network outside the parasite. Finally, the mAbs did not react with P. falciparum
      sporozoites, indicating that the rhoptries of merozoites and sporozoites, the two
      invasive stages of the malaria life-cycle are equipped with distinct sets of
      proteins.

PMID- 7517518
TI  - Toxoplasma gondii-structure variations of the antigen P30.
AB  - The major surface immunodominant antigen (P30) of Toxoplasma gondii was purified
      by two methods (i) SDS-PAGE and (ii) immunoaffinity chromatography. The secondary
      elements within this protein were assessed by circular dichroism and spectra
      obtained were compared to those proposed by Manavalan & Johnson (1983). The
      results allowed us to determine an all beta protein status for this antigen. This
      experimental result was in agreement with the predicted secondary structures
      deduced from the P30 primary sequence. Modifications in conformation according to
      pH and temperature were recorded without any change in immunoactivity. The
      epitope, which was always recognized by a monoclonal antibody against P30, could
      be a linear epitope.

PMID- 7517520
TI  - North American Society of Pacing and Electrophysiology (NASPE) 15th annual
      scientific sessions. Nashville, Tennessee, May 11-14, 1994. Abstracts.

PMID- 7517519
TI  - Immune responses of Texel sheep to excretory/secretory products of adult
      Haemonchus contortus.
AB  - The excretory/secretory (E/S) products of adult Haemonchus contortus comprise of
      at least 15 polypeptides with molecular weights ranging from 10 to > 100 kDa.
      These E/S products induce an immune response in infected Texel sheep, as
      demonstrated by specific IgG1 levels and a significant lymphocyte proliferation
      index. Moreover, immunoblotting analysis revealed that sera of primary H.
      contortus-infected sheep specifically recognize a 24 kDa E/S product. In
      addition, sera of challenged sheep react strongly with a 15 kDa E/S product. The
      other E/S products of H. contortus showed immunoreactivity with serum samples of
      Haemonchus-infected sheep as well as with samples of sheep harbouring other
      trichostrongylid infections. These cross-reacting epitopes are the main cause of
      the lack of specificity of an E/S material-based ELISA. This ELISA can
      differentiate Haemonchus infections from Nematodirus battus infections, but not
      from Ostertagia circumcincta or Trichostrongylus colubriformis infections.

PMID- 7517521
TI  - Patterns of catheter ablation practice in the United States: results of the 1992
      NASPE survey. North American Society of Pacing and Electrophysiology.
AB  - Any conclusion drawn must be made within the context of all the limitations
      inherent in a voluntary retrospective survey. The primary purpose of this survey
      is to provide a general picture of current catheter ablative procedure practiced
      in the United States. This is felt to be of value in calling attention to
      significant trends and to highlight those areas in which improvement is needed.
      Improvement may be required in terms of operator experience as well as improved
      catheters and energy delivery systems. The striking finding was a plateau in
      total number of procedures from 1991 to 1992. The decline in numbers of patients
      undergoing ablation of accessory pathways was more than compensated for by
      impressive growth in numbers of patients undergoing ablative procedures for
      atrioventricular nodal reentry, atrial tachycardia/atrial flutter, and
      ventricular tachycardia. The ablative data suggest that continued improvements
      are needed for successful ablation of patients with right-sided accessory
      pathways. The anatomy of the tricuspid annulus makes for difficulty in achieving
      catheter stability and this report highlights the need for better catheters
      designed for right-sided pathway ablation. Equally concerning is the incidence of
      procedure related deaths (0.2%) and significant complications (2.1%) for patients
      with accessory pathways. This is no doubt related to the need for left heart
      catheterization in the majority of patients. The latter involves either
      retrograde aortic passage of the relatively stiff ablation catheters or use of
      transseptal puncture. In addition, we found that 35 of the 164 centers performed
      less than 20 procedures a year and low volume centers had a higher incidence of
      complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517522
TI  - Strength-interval curves in canine myocardium at very short cycle lengths.
AB  - While ventricular electrophysiological properties have been intensively studied
      at normal heart rates, little is known about these properties at the very short
      cycle lengths (approximately 100 msec), which are present in ventricular
      fibrillation. We examined refractoriness in the right ventricles of six dogs at
      stimulation intervals of 80 to 300 msec. Starting at 300 msec, the basic (S1)
      cycle length was decremented by 10 msec each beat to 200, 150, or 125 msec. A 1
      msec premature (S2) stimulus of 1, 5, 10, or 20 mA was then introduced. The S1-S2
      interval was decremented until capture was lost. The refractory period was
      considered to be the shortest interval that captured the heart for each S2
      strength. Only pacing episodes that did not induce fibrillation were included.
      Strength-interval curves maintained the same hyperbolic shape but shifted to very
      short refractory periods as the S1-S1 interval was decreased. At the shortest S1
      S1 intervals, premature stimuli were capable of capturing the heart without
      inducing ventricular fibrillation for S1-S2 intervals as short as 83 +/- 3 msec.
      Thus, decremental rapid pacing can produce refractory periods shorter than the
      cycle length during ventricular fibrillation. This finding suggests that there is
      no need to postulate a discontinuous jump to new electrophysiological properties
      or relationships at the onset of fibrillation, but that the capability for
      fibrillation is an integral part of normal electrophysiological parameters when
      they are pushed to values that do not occur normally. The results of this study
      should be useful in the further development of active membrane models and
      cellular automata models of cellular electrical behavior.

PMID- 7517523
TI  - Short AV interval VDD pacing does not prevent tilt induced vasovagal syncope in
      patients with cardioinhibitory vasovagal syndrome.
AB  - Eleven subjects (mean age 50 years, range 33-71 years), who had previously
      received permanent dual chamber pacemakers for cardioinhibitory vasovagal
      syncope, underwent paired Westminster protocol tilt tests, one with short AV
      delay VDD pacing and one without pacing, to test the hypothesis that continuous
      ventricular pacing would prevent the cardiac initiation of vasovagal syncope.
      Nine (82%) of the paced tilts produced positive vasovagal outcomes compared with
      seven (64%) of the unpaced tilts. No important differences in the heart rate or
      blood pressure behavior during tilt or the time to positive vasovagal outcomes
      were observed between the paired tilts. There was more accelerated
      syncope/presyncope once symptoms had developed during the paced tilts of subjects
      in whom both study tilts were positive, although this did not reach statistical
      significance (P = 0.054). This study shows that atrial synchronous ventricular
      pacing does not prevent the initiation, or progression, of tilt induced vasovagal
      syncope in predisposed subjects.

PMID- 7517524
TI  - Comparison of spectral temporal mapping to the time domain signal-averaged
      electrocardiogram in normal subjects and in patients with coronary artery disease
      and sustained ventricular tachycardia.
AB  - Spectral temporal mapping is a new form of analysis for signal-averaged
      electrocardiography, which has the goal of improving the sensitivity and
      specificity of traditional time domain analysis. Our objective in this study was
      to determine the effectiveness of one form of spectral temporal mapping, in the
      face of conflicting results that have so far been reported with this approach. We
      prospectively performed both spectral temporal mapping and time domain analysis
      on 50 patients with a history of coronary artery disease and inducible sustained
      monomorphic ventricular tachycardia (Group 1) and on 25 normal subjects with
      normal electrocardiograms and no history of heart disease (Group 2). We found
      that for the 40 Group 1 patients without bundle branch block (Group 1A), the
      sensitivity of spectral temporal mapping was lower than that for time domain
      analysis (45% vs 80%, P < 0.005). The results of spectral temporal mapping for
      Group 1A patients were similar to that for all of Group 1. The sensitivity of
      spectral temporal mapping was 60% (n = 10) for patients with bundle branch block
      (Group 1B). The specificity noted in Group 2 was 88% by each means of analysis;
      however, no one in Group 2 had an abnormal finding by time domain and spectral
      temporal mapping. Attempts to optimize the criteria for an abnormal spectral
      analysis did not identify criteria that were superior to those currently in use.
      We conclude that spectral temporal mapping using Haberl's method is inferior to
      time domain analysis in identifying patients with sustained ventricular
      tachycardia, but may be of value in conjunction with the traditional approach in
      identifying normal subjects.

PMID- 7517526
TI  - The anatomical determinants for the design of intracardiac mapping and ablation
      catheters.
AB  - An important factor in the efficient and successful completion of the ablation
      procedure is the design characteristics of the mapping/ablation catheters. These
      procedures are often hampered by the inability to maneuver the catheter to the
      desired location, in part because the catheters only have a single plane
      deflection capability and are not designed for the specific cardiac anatomical
      structures that contain the arrhythmogenic substrate. Single and Biplane
      Deflectable Catheters: Using measurements taken from six normal human cadaver
      hearts, ablation catheter design characteristics are presented for posterior,
      posterior septal, lateral, and posterior lateral pathways for retrograde and
      transseptal approaches. Three catheter designs based on anatomical
      characteristics were also evaluated. Pigtail Catheter: This catheter adapts to
      the atrial side of the mitral ring and improves positioning and stability for
      mapping and ablation of left-sided accessory pathways. Loop Catheter: This
      catheter is positioned at the perivalvular tricuspid ring and provides
      simultaneous mapping and ablation capabilities without the need to move the
      catheter or the need for additional catheters. Rotating Tip Catheter: The tip of
      this catheter is made up of three elongated teeth, which were curved 120 degrees
      apart into the rotating tip electrode. This electrode was designed to negotiate
      the surfaces of the atrial and intraventricular chambers. It is capable of
      discrete movements and has a large electrode-tissue contact area for the ablation
      of atrial and ventricular arrhythmias. Catheter designs presented in this article
      are based on the ability of the catheter to adapt to the anatomical location of
      the arrhythmogenic tissue as well as the maneuverability of the catheter's
      mapping and ablation electrodes. An anatomical approach to the design of ablation
      catheter technology is likely to reduce the x-ray radiation exposure for patient
      and operator, and may further increase the success rate of the procedure.

PMID- 7517525
TI  - The effects of pacing site on left ventricular epicardial surface velocity
      patterns during systole.
AB  - Changes in epicardial LV velocity patterns during isovolumic contraction and
      ejection as induced by ventricular pacing were studied in 15 canines. A
      noninvasive imaging technique that provided high temporal resolution was used to
      study the timing of an outward expansion of the LV during isovolumic contraction
      and the propagation pattern of an inward LV velocity wavefront during ejection.
      With this technique, surface displacements were measured (+/- 0.1 mm SD) at 50-70
      locations on the LV free wall at 5-msec intervals. Velocities were calculated by
      differentiating the surface displacement waveforms and an interpolation procedure
      was used to provide detailed color coded velocity maps of the LV surface. LV
      surface velocities were determined from data obtained during closed-chest
      endocardial pacing from each of four sites: right atrium, right ventricular apex,
      left ventricular apex, and right ventricular outflow tract. These surface
      velocities showed a distinct spatial and temporal pattern for each pacing site.
      The results show that this noninvasive mapping procedure has potential for
      determining the location of an ectopic ventricular focus.

PMID- 7517527
TI  - Inappropriate sinus tachycardia following radiofrequency ablation of AV nodal
      tachycardia: incidence and clinical significance.
AB  - The incidence and consequences of inappropriate sinus tachycardia following
      modification of the AV nodal area with radiofrequency energy were prospectively
      studied in a consecutive series of 118 patients. Twelve (10%) patients developed
      this complication, which persisted less than 1 week in all but three patients.
      Inappropriate sinus tachycardia was only observed after fast pathway ablation.
      Only four patients required temporary treatment with a beta blocker.

PMID- 7517529
TI  - Spiral waves in a computer model of cardiac excitation.
AB  - Spiral excitation fronts have been demonstrated in association with reentry in a
      computer model of propagated excitation. Fronts were initiated by the reentrant
      circuits but the spiral configurations themselves occurred outside the circuits.
      Excitation initiated near the initial portion of reentrant circuits propagated
      greater distances during a particular time period than excitation initiated from
      later portions of the circuit. This resulted in spiral configuration of
      excitation fronts in which the front was located at increasing distance from the
      latest initiating event. Excitation fronts that did not themselves have spiral
      configurations in certain matrices were identifiable as parts of spiral
      configurations that occurred when the same reentrant events were present in other
      matrices. Spiral waves were initiated by either leading circle reentry associated
      with functional block to propagation or reentry associated with structural
      obstacles. They also occurred in the presence of initially uniform refractory
      periods and resulted in self-sustained reentrant excitation. This however,
      required particular conditions of excitation such that recovery times constituted
      a functional block permitting leading circle reentry.

PMID- 7517530
TI  - Plasma levels of natriuretic peptides during ventricular pacing in patients with
      a dual chamber pacemaker.
AB  - The mechanism(s) responsible for the release of brain natriuretic peptide (BNP),
      a cardiac hormone of ventricular origin, are still not completely understood. We
      measured plasma atrial natriuretic peptide (ANP) and BNP in 15 subjects (10 men,
      mean age 67 +/- 3 years) with a dual chamber pacemaker and unimpaired heart
      function during ventricular pacing, which is known to induce an increase in
      atrial pressure and plasma ANP concentration. Under ECG monitoring, all subjects
      received sequential atrioventricular pacing for 30 minutes and ventricular pacing
      for 30 minutes, at the same rate of 80 beats/min. Arterial pressure and plasma
      BNP and ANP levels were measured every 10 minutes throughout the study.
      Ventricular pacing led to atrioventricular dissociation in eight subjects and to
      retrograde ventriculo-atrial conduction in seven. Arterial pressure remained
      unchanged in all subjects. In the group with atrioventricular dissociation,
      plasma ANP increased from 10.14 +/- 0.58 to 16.72 +/- 0.92 fmol/mL at the 60th
      minute (P < 0.0001), whereas plasma BNP did not change at all (from 1.26 +/- 0.07
      to 1.16 +/- 0.09 fmol/mL). In the group with retrograde conduction, plasma ANP
      concentration doubled (from 10.95 +/- 1.66 to 21.40 +/- 1.51 fmol/mL, P <
      0.0001), BNP increased 1.5-fold (from 1.16 +/- 0.06 to 1.64 +/- 0.14 fmol/mL, P <
      0.001), and the ANP:BNP ratio augmented from 10:1 to 13.4:1. These results
      indicate that the release of ANP and BNP is regulated by different mechanisms,
      supporting the view that there is a dual natriuretic peptide system, comprising
      ANP from the atria and BNP from the ventricles.

PMID- 7517528
TI  - Evaluation of outpatients experiencing implantable cardioverter defibrillator
      shocks associated with minimal symptoms.
AB  - Patients receiving minimally symptomatic shocks from their implantable
      cardioverter defibrillators were studied prospectively using transtelephonic ECG
      loop monitoring. The time course to the first subsequent shock was evaluated.
      Twenty-nine consecutive patients who received a shock preceded by mild
      palpitations or no symptoms were given a transtelephonic ECG loop monitor and
      instructed to activate the monitor if a subsequent shock occurred. Kaplan-Meier
      analysis was used to quantitate the time to first shock during the study period.
      The point estimate +/- standard error of patients receiving a shock during the
      study period was 31% +/- 9% at 30 days, 41% +/- 9% at 60 days, and 60% +/- 9% at
      120 days. The ECG was successfully transmitted in 7 of 13 patients who had shocks
      in the 60-day monitoring period, and demonstrated inappropriate shocks in 6 of 7.
      Determination of the cause of shock led to a change in subsequent management in
      all 7 patients. We conclude that the incidence of inappropriate shocks may be
      higher than estimated previously in patients with minimal symptoms prior to the
      shock. There are thousands of patients with implantable cardioverter
      defibrillators that have no storage function for treated tachycardias;
      transtelephonic ECG loop monitoring can determine the cause of implantable
      cardioverter defibrillator discharge in these patients, and the diagnosis is
      invaluable in their management.

PMID- 7517532
TI  - Risk of sudden arrhythmic death in the Wolff-Parkinson-White syndrome: current
      perspectives.

PMID- 7517531
TI  - VDD pacing at short atrioventricular intervals does not improve cardiac output in
      patients with dilated heart failure.
AB  - Atrial synchronous pacing with short, nonphysiological atrioventricular (AV)
      intervals has been reported to increase cardiac output in selected patients with
      severe dilated heart failure. The aim of this study was to determine the acute
      effect of atrial synchronous pacing with short AV intervals in a consecutive
      series of patients with dilated heart failure. Twelve patients with a mean
      ejection fraction of 21% +/- standard error 2.5% were studied. Pacing catheters
      were placed in the high right atrium and right ventricular apex and a balloon
      flotation catheter in the pulmonary artery for measurement of cardiac output.
      Simultaneous transthoracic echocardiography was performed for measurement of left
      ventricular filling time and mitral regurgitation. In a randomized crossover
      design, measurements were made during VDD pacing at programmed AV intervals of
      100 and 60 msec and during a control period in sinus rhythm. Left ventricular
      filling time increased at AV intervals of 100 and 60 msec (mean difference 37 +/-
      9 and 34 +/- 11 msec, respectively, both P < 0.01 compared to control). Despite
      increases in ventricular filling time, stroke, and cardiac index declined with
      short atrioventricular intervals (at an AV interval of 60 msec, stroke index fell
      by 2.1 +/- 0.5 mL/m2, P < 0.05 and cardiac index by 125 +/- 45 mL/m2; P = NS).
      Heart rate was unchanged at both AV intervals (78 +/- 4.9 at control, 78 +/- 5.2
      at 100 msec and 79 +/- 4.9 beats/min at 60 msec; P = NS).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7517533
TI  - Maneuvering on the Internet.

PMID- 7517534
TI  - Service consolidation--an idea whose time is coming.

PMID- 7517535
TI  - Radiofrequency catheter ablation of an accessory pathway in a young man with
      dextroversion.
AB  - We report an observation of a radiofrequency catheter ablation of an accessory
      pathway (AP) in a patient with Wolff-Parkinson-White syndrome (WPW) and
      dextroversion. Atrioventricular rings were mapped by the ablation catheter to
      locate the shortest local atrioventricular conduction time in sinus rhythm and
      ventriculoatrial conduction time during orthodromic tachycardia or ventricular
      pacing. Successful ablation confirmed a right posteroseptal AP localization.
      Thus, the electrocardiographic modifications due to an AP in this location in the
      presence of dextroversion were defined.

PMID- 7517537
TI  - Sinus dysrhythmia in Kearns-Sayre syndrome.
AB  - Kearns-Sayre syndrome is the triad of progressive external ophthalmoplegia,
      pigmentary retinopathy, and complete AV block. The etiology is unknown, but is
      thought to be due to a mitochondrial DNA deletion. Reported electrocardiographic
      abnormalities include first-degree AV block, fascicular blocks, and complete
      heart block, as well as non-specific S-T segment changes and T wave
      abnormalities, but has not included sinus node dysfunction. We report a case with
      episodes of sinus arrest in an asymptomatic patient with Kearns-Sayre syndrome
      resulting in pauses lasting up to 6 seconds.

PMID- 7517538
TI  - Pacemaker communications.

PMID- 7517536
TI  - Radiofrequency ablation of an accessory pathway in a patient with corrected
      Ebstein's anomaly.
AB  - Ebstein's anomaly of the tricuspid valve has a known association with the Wolff
      Parkinson-White syndrome. Radiofrequency ablation has become the treatment of
      choice for the latter, but there have been no reports of the feasibility of this
      procedure after tricuspid valve replacement. We present a patient who first
      exhibited evidence of intermittent preexcitation and associated symptomatic
      arrhythmia 9 years after tricuspid valve replacement for Ebstein's anomaly, and
      describe the challenges posed by this case.

PMID- 7517540
TI  - STIMAREC report.

PMID- 7517539
TI  - Improvement of cardiac function in patients with severe congestive heart failure
      and coronary artery disease by dual chamber pacing with shortened AV delay.

PMID- 7517541
TI  - Effect of naftopidil on urethral obstruction in benign prostatic hyperplasia:
      assessment by urodynamic studies.
AB  - Thirty-two patients with voiding dysfunction attributable to symptomatic benign
      prostatic hyperplasia were treated with naftopidil, an alpha 1-blocker, at doses
      of 25-75 mg/day for 4-6 weeks. The efficacy of the drug was assessed from the
      changes in urinary symptoms and urodynamic data. Total symptom scores were
      significantly reduced after treatment (P < 0.001). Average flow rate and maximum
      flow rate were significantly increased (P < 0.001 and P < 0.001, respectively),
      and residual urine volume, residual urine rate (ratio of residual urine
      volume/sum of voided volume and residual urine volume), and maximum urethral
      closure pressure were significantly (P < 0.05, P < 0.01, and P < 0.05,
      respectively) reduced, and at bladder capacity, the first desire to void was
      significantly (P < 0.05) increased. The pressure/flow study demonstrated no
      changes in intravesical pressure at maximum flow, but a significant (P < 0.05)
      reduction in minimum urethral resistance. A mild side effect (dizziness) was
      noted in one patient (3.3%), which soon disappeared after the dose was decreased.
      The efficacy was good or excellent in 21 of 30 patients (70.0%). The drug was
      evaluated to be promising in the treatment of bladder outlet obstruction due to
      benign prostatic hyperplasia.

PMID- 7517542
TI  - Prostatic cancer and BPH.

PMID- 7517543
TI  - Inhibition of pancreatic exocrine secretion by galanin.
AB  - The influence of extrapancreatic nerves on the inhibition of meal- and
      secretogogue-induced pancreatic secretion by galanin was studied in conscious
      dogs. Chronic pancreatic fistulae were created in five mongrel dogs and a second
      group of five dogs also underwent complete pancreatic denervation. After
      recovery, galanin dose response (150-1,200 pmol/kg/h) revealed that 600 pmol/kg/h
      was the lowest dose of galanin to significantly inhibit pancreatic exocrine
      secretion. Pancreatic responses to a mixed meal, cholecystokinin (CCK) dose
      response (12.5-200 ng/kg/h), and secretin dose response (16-500 ng/kg/h) were
      determined. The experiments were then replicated with a continuous background
      infusion of galanin (600 pmol/kg/h). Galanin inhibited meal-, CCK-, and secretin
      induced bicarbonate outputs in both the innervated and denervated pancreas.
      Galanin also inhibited meal- and CCK-induced protein responses in both groups. We
      conclude that extrapancreatic nerves do not mediate the inhibitory effects of
      galanin.

PMID- 7517544
TI  - Therapeutic and protective effect of subcutaneous injections of L-364,718 on
      caerulein-induced acute pancreatitis.
AB  - The prophylactic and therapeutic effects of a potent cholecystokinin (CCK)
      receptor antagonist, L-364,718, on acute pancreatitis induced by caerulein were
      evaluated, analyzing morphologic and functional pancreatic parameters jointly.
      Edematous pancreatitis was induced by four subcutaneous injections of caerulein
      (20 micrograms/kg) in rats at 1-h intervals. Prophylactic administration of L
      364,718 (0.1 mg/kg) prevented rise in serum amylase levels, interstitial edema,
      vacuolization, and impairment of pancreatic enzyme secretion that accompany
      caerulein-induced acute pancreatitis. After 7 days, a spontaneous regression of
      the morphologic alterations caused by caerulein-induced acute pancreatitis
      occurs; however, recovery of the secretory function of the pancreas was only
      reached after this period of time when L-364,718 was administered therapeutically
      (0.1 mg/kg/day). Prophylactically or therapeutically administered, L-364,718
      exerts a beneficial effect on caerulein-induced acute pancreatitis, indicating
      that CCK (exogenous or endogenous) plays an important role in the development of
      this pathology.

PMID- 7517545
TI  - Apolipoprotein E polymorphism in patients with acute pancreatitis.
AB  - We have shown that patients with previous acute pancreatitis (AP) may have an
      abnormal catabolism of chylomicron remnants (CMR). Because apoprotein E (Apo E)
      genetic polymorphism has an important influence on CMR clearance, we compared
      frequency distribution of Apo E phenotypes in 52 patients with AP, 109 patients
      with gallstones, and 110 control subjects. Apo E phenotypes were detected by
      isoelectric focusing and immunoblotting. After adjusting for differences in age
      and gender, fasting triglyceride level was comparable between the study groups.
      The frequency distribution of Apo E phenotypes was not different between the
      three study groups and it was in Hardy-Weinberg equilibrium. The gene frequency
      for Apo E2 was 0.212, 0.273, and 0.243 in AP, gallstone, and control group,
      respectively. For Apo E3 it was 0.701, 0.627, and 0.674, and for Apo E4 0.090,
      0.100, and 0.083 in the same groups, respectively. Differences were not
      statistically significant (chi 2). In conclusion, the abnormal catabolism of CMR
      in patients with AP is not attributable to Apo E polymorphism. An alternative
      explanation may be sought in the activity of the recently identified hepatocytic
      Apo E receptor [LDL-related receptor protein (LRP)].

PMID- 7517546
TI  - The aquaporin family of molecular water channels.

PMID- 7517547
TI  - Cyclic nucleotide- and inositol phosphate-gated ion channels in lobster olfactory
      receptor neurons.
AB  - The idea of having two second messenger pathways in olfaction, one mediated by
      cAMP and the other by inositol 1,4,5-trisphosphate, is supported by evidence that
      both second messengers directly activate distinct ion channels in the outer
      dendrite of lobster olfactory receptor neurons. Evidence that both types of
      second messenger-gated channels can occur in the same patch of membrane suggests
      that channels of both types can be expressed in one neuron. Evidence of more than
      one type of inositol phosphate-gated channel in this highly specialized region of
      the neuron furthers the idea that the output of individual olfactory receptor
      cells is regulated through multiple effectors and allows that effector diversity
      may contribute to functional diversity among olfactory receptor cells.

PMID- 7517549
TI  - Three distinct human thymopoietins are derived from alternatively spliced mRNAs.
AB  - Thymopoietin (TP) was originally isolated as a 5-kDa 49-aa protein from bovine
      thymus in studies of the effects of thymic extracts on neuromuscular transmission
      and was subsequently observed to affect T-cell differentiation and function. We
      now report the isolation of cDNA clones for three alternatively spliced mRNAs
      that encode three distinct human T-cell TPs. Proteins encoded by these mRNAs,
      which we have named TP alpha (75 kDa), TP beta (51 kDa), and TP gamma (39 kDa),
      contain identical N-terminal regions, including sequences nearly identical to
      that of the originally isolated 49-aa protein, but divergent C-terminal regions.
      TP mRNAs are expressed in many tissues, most abundantly in adult thymus and fetal
      liver of the tissues so far examined. Distinct structural domains and functional
      motifs in TPs alpha, beta, and gamma suggest that the proteins have unique
      functions and may be directed to distinct subcellular compartments.

PMID- 7517550
TI  - Structure of a single-chain antibody variable domain (Fv) fragment complexed with
      a carbohydrate antigen at 1.7-A resolution.
AB  - We describe here the 1.7-A resolution structure of a single-chain antibody
      variable domain (scFv) molecule, based on the carbohydrate-binding antibody Se155
      4, complexed with the trisaccharide ligand alpha-D-Gal(1-->2)[alpha-D-Abe(1-
      >3)]alpha-D-Manp1-->OMe, where Abe is abequose. The scFv expressed in Escherichia
      coli has the variable region light chain to heavy chain polarity with the domains
      connected by a 19-residue linker. Although the linker is partially disordered in
      the crystal, the packing of the molecules suggests a monomeric state of the scFv.
      The carbohydrate adopts a different conformation about the Man-Gal linkage than
      was observed previously in the Fab-trisaccharide complex. Instead of a direct
      hydrogen bond between O2Abe and O2Gal, these two atoms are bridged by a water
      molecule in the present complex.

PMID- 7517548
TI  - Molecular cloning and expression of a member of the aquaporin family with
      permeability to glycerol and urea in addition to water expressed at the
      basolateral membrane of kidney collecting duct cells.
AB  - Water transport in highly water-permeable membranes is conducted by water
      selective pores--namely, water channels. The recent cloning of water channels
      revealed the water-selective characteristics of these proteins when expressed in
      Xenopus oocytes or reconstituted in liposomes. Currently, it is assumed that the
      function of water channels is to transport only water. We now report the cloning
      of a member of the water channel that also transports nonionic small molecules
      such as urea and glycerol. We named this channel aquaporin 3 (AQP3) for its
      predominant water permeability. AQP3 has amino acid sequence identity with major
      intrinsic protein (MIP) family proteins including AQP-channel-forming integral
      membrane protein, AQP-collecting duct, MIP, AQP-gamma tonoplast intrinsic
      protein, nodulin 26, and glycerol facilitator (33-42%). Thus, AQP3 is an
      additional member of the MIP family. Osmotic water permeability of Xenopus
      oocytes measured by videomicroscopy was 10-fold higher in oocytes injected with
      AQP3 transcript than with water-injected oocytes. The increase in osmotic water
      permeability was inhibited by HgCl2, and this effect was reversed by a reducing
      agent, 2-mercaptoethanol. Although to a smaller degree, AQP3 also facilitated the
      transport of nonionic small solutes such as urea and glycerol, while the
      previously cloned water channels are permeable only to water when expressed in
      Xenopus oocytes. AQP3 mRNA was expressed abundantly in kidney medulla and colon.
      In kidney, it was exclusively immunolocalized at the basolateral membrane of
      collecting duct cells. AQP3 may function as a water and urea exit mechanism in
      antidiuresis in collecting duct cells.

PMID- 7517552
TI  - Axonal transport of herpes simplex virions to epidermal cells: evidence for a
      specialized mode of virus transport and assembly.
AB  - To examine the transmission of herpes simplex virus (HSV) from axon to epidermal
      cell, an in vitro model was constructed consisting of human fetal dorsal root
      ganglia cultured in the central chamber of a dual-chamber tissue culture system
      separated from autologous skin explants in an exterior chamber by concentric
      steel cylinders adhering to the substratum through silicon grease and agarose.
      Axons grew through the agarose viral diffusion barrier and terminated on
      epidermal cells in the exterior chamber. After inoculation of HSV onto dorsal
      root ganglia, anterograde axonal transport of glycoprotein and nucleocapsid
      antigen was observed by confocal microscopy to appear in exterior chamber axons
      within 12 h and in epidermal cells within 16 h, moving at 2-3 mm/h. Although both
      enveloped and unenveloped nucleocapsids were observed in the neuronal soma by
      transmission electron microscopy, only nucleocapsids were observed in the axons,
      closely associated with microtubules. Nodule formation at the surface of HSV
      infected axons, becoming more dense at the axon terminus on epidermal cells, and
      patches of axolemmal HSV glycoprotein D expression were observed by scanning
      (immuno)electron microscopy, probably representing virus emerging from the
      axolemma. These findings strongly suggest a specialized mode of viral transport,
      assembly, and egress in sensory neurons: microtubule-associated intermediate-fast
      anterograde axonal transport of unenveloped nucleocapsids with separate transport
      of glycoproteins to the distal regions of the axon and assembly prior to virus
      emergence at the axon terminus.

PMID- 7517551
TI  - Nitric oxide mediates sexual behavior in female rats.
AB  - Nitric oxide (NO), an active free radical formed during the conversion of
      arginine to citrulline by the enzyme NO synthase (NOS), mediates vasorelaxation,
      cytotoxicity, and neurotransmission. Neurons containing NOS (NOergic) are located
      in the hypothalamus. These NOergic neurons control the release of several
      hypothalamic peptides. Release of NO from these NOergic neurons stimulates
      pulsatile release of luteinizing hormone-releasing hormone (LHRH) in vivo and
      LHRH release in vitro. LHRH not only induces LH release, which induces ovulation,
      but also facilitates female sexual behavior. Sexual behavior can be induced
      reliably in estrogen-primed ovariectomized female rats by progesterone (P). This
      behavior consists of proceptive behavior to attract the male and the assumption
      of a clear characteristic posture, lordosis, when mounted by the male. To
      ascertain the role of NO in the control of sexual behavior in female rats, an
      inhibitor of NOS, NG-monomethyl-L-arginine was microinjected into the third
      cerebral ventricle (3V) of conscious, ovariectomized, estrogen-primed rats with
      indwelling cannulae. NG-Monomethyl-L-arginine (10-1000 micrograms) prevented P
      facilitated lordosis when administered intracerebroventricularly into the 3V, 20
      min prior to the 3V injection of P. NG-Monomethyl-D-arginine, which does not
      inhibit NOS, did not inhibit lordosis under the same experimental conditions.
      Microinjection into the 3V of sodium nitroprusside (SNP), which spontaneously
      releases NO, facilitated lordosis in estrogen-primed rats in the absence of P.
      The facilitation of lordosis induced by either P or SNP was prevented by
      intracerebroventricular injection of hemoglobin, which binds NO. Lordosis
      facilitated by P or SNP was blocked by injection of LHRH antiserum into the 3V.
      The results are interpreted to mean that the P-facilitated lordosis response is
      mediated by LHRH release. Furthermore, since NO release from SNP also facilitates
      lordosis in the absence of P and this response could be blocked by LHRH
      antiserum, we conclude that P brings about the release of NO, which stimulates
      LHRH release that facilitates lordosis. Thus, the results indicate that NO
      induces LHRH release and that LHRH then plays a crucial role in mediation of
      sexual behavior in the female rats.

PMID- 7517554
TI  - Reverse chemical mutagenesis: identification of the mutagenic lesions resulting
      from reactive oxygen species-mediated damage to DNA.
AB  - An understanding of the contribution of reactive oxygen species to mutagenesis
      has been hampered by the vast number of different chemical modifications they
      cause in DNA. Even though many of these DNA alterations have been catalogued, the
      identification of specific lesions that cause mutations has depended on testing
      one modification at a time. In this study we present another approach to identify
      key mutagenic lesions from a pool of oxidatively modified nucleotides. dCTP was
      treated with an oxygen radical-generating system containing FeSO4, H2O2, and
      ascorbic acid. The modification products were separated by reverse-phase and
      anion-exchange HPLC and then incorporated by human immunodeficiency virus reverse
      transcriptase into a DNA that contains a target gene for scoring for mutations.
      One of the mutagenic species isolated was identified as 5-hydroxy-2'
      deoxycytidine. It is incorporated efficiently into DNA and causes C-->T
      transitions in Escherichia coli at a frequency of 2.5%, which is more mutagenic
      than any previously identified oxidative DNA lesion.

PMID- 7517553
TI  - Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT)
      inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV
      1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants.
AB  - Mutant HIV-1 that expresses a Glu138-->Lys substitution in its RT [(E138K)RT] is
      resistant to the HIV-1-specific RT inhibitor 2',5'-bis-O-(tert
      butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"
      dioxide)pyrimidine (TSAO). However, cell cultures infected with this mutant were
      completely protected against virus-mediated destruction by micromolar
      concentrations of the HIV-1-specific RT inhibitors tetrahydroimidazo[4,5,1
      jk][1,4]benzodiazepin-2(1H)-one and -thione (TIBO), nevirapine, and
      bis(heteroaryl)piperazine (BHAP). In contrast, cells infected with a virus mutant
      that expresses a Tyr181-->Cys substitution in its RT [(Y181C)RT] were not
      protected by nevirapine and TIBO and were only temporarily protected by BHAP. HIV
      1 mutant that emerged under the latter conditions contained a Cys181-->Ile
      substitution in their RT [(LC181I)RT]. This mutant proved highly resistant to all
      HIV-1-specific RT inhibitors tested, except for several 1-(2-hydroxyethoxymethyl)
      6-(phenylthio)thymine (HEPT) derivatives. When recombinant (C181I)RT was
      evaluated for susceptibility to the HIV-1-specific RT inhibitors, it was
      resistant to all inhibitors except the HEPT compounds. Since a (Y181F)RT HIV
      mutant strain was isolated from cells infected with (Y181C)RT HIV-1 and treated
      with BHAP, we postulate that the Ile codon was derived from a Cys-->Phe
      transversion mutation (TGT-->TTT), followed by a Phe-->Ile transversion mutation
      (TTT-->ATT).

PMID- 7517556
TI  - On producing more complexity than entropy in replication.
AB  - RNA replication in the bacteriophage Q beta system can, in principle, transmit
      sequence complexity at a higher rate than it increases entropy. Expanding the
      variety of nucleotides, through novel base-pair interactions, would move the
      threshold at which synthesis produces more complexity than entropy away from near
      equilibrium while accelerating the system approach to equilibrium. A decrease in
      sequence complexity during polymerization, leading to a many-to-one monomer
      correspondence with template, cannot be reversed, owing to symmetry restrictions.
      In terms of the kinetic mechanism, uncertainty associated with the the path of
      depolymerization yields a path entropy which selectively prolongs the reverse
      reaction. Together with an elevation in thermodynamic entropy, therefore, there
      are two possible sources of irreversibility in a physical process. Some
      implications of kinetic irreversibility are considered in relation to the second
      law of thermodynamics and to the processing and translation of mRNA.

PMID- 7517555
TI  - Two-photon scanning photochemical microscopy: mapping ligand-gated ion channel
      distributions.
AB  - The locations and densities of ionotropic membrane receptors, which are
      responsible for receiving synaptic transmission throughout the nervous system,
      are of prime importance in understanding the function of neural circuits. It is
      shown that the highly localized liberation of "caged" neurotransmitters by two
      photon absorption-mediated photoactivation can be used in conjunction with
      recording the induced whole-cell current to determine the distribution of ligand
      gated ion channels. The technique is potentially sensitive enough to detect
      individual channels with diffraction-limited spatial resolution. Images of the
      distribution of nicotinic acetylcholine receptors on cultured BC3H1 cells were
      obtained using a photoactivatable precursor of the nicotinic agonist
      carbamoylcholine.

PMID- 7517559
TI  - Alternative splicing generates secretory isoforms of human CD1.
AB  - Human CD1 genes are a family of five non-polymorphic genes that, although
      homologous to both class I and II major histocompatibility complex genes, map to
      chromosome 1. Only three of the antigens, CD1a, -b, and -c, have been clustered
      with monoclonal antibodies. They are noncovalently associated with beta 2
      microglobulin and may function as nonclassical antigen-presenting molecules. Here
      we analyze their expression in mouse myeloma transfectants and human thymocytes
      and find mRNA splicing complexity. This manifests itself as incomplete splicing,
      alternative splicing, utilization of cryptic splice sites, and the generation of
      alternative reading frames. In the case of CD1A transfectants, we demonstrate
      that the major protein product is secreted and show by amino acid sequence
      analysis that this is derived from an unspliced transcript. A second major CD1a
      component appears to be retained intracellularly. The production of alternatively
      spliced transcripts in the thymus is not a feature of all CD1 genes. Although in
      the case of CD1A only the transcript encoding the cell surface CD1a isoform is
      found, CD1C and -E produce complex intrathymic splicing patterns. The CD1C
      transcripts predict the expression of a secreted CD1c isoform in the human
      thymus, which we detect in CD1C transfectant culture supernatants. CD1 gene
      expression is thus characterized by considerable splicing complexity, and the
      difference between the splicing patterns found in different environments suggests
      that this is tissue specific.

PMID- 7517558
TI  - Drosophila telomere transposon HeT-A produces a transcript with tightly bound
      protein.
AB  - Telomeres from Drosophila appear to be very different from those of other
      organisms. A transposable element, HeT-A, plays a major role in forming telomeres
      and may be the sole structural element, since telomerase-generated repeats are
      not found. The structure of the HeT-A element, deduced from cloned fragments of
      DNA, suggests that transposition of the element is mediated by a polyadenylylated
      RNA intermediate. We now report analyses of HeT-A transcripts. The major RNA is
      of the appropriate size and strandedness to serve as a transposition
      intermediate. This RNA is found in cultured cells and in intact flies and is
      unusual in that it is associated with protein after treatments that apparently
      remove all protein from other RNAs.

PMID- 7517560
TI  - Delineation of a T-cell activation motif required for binding of protein tyrosine
      kinases containing tandem SH2 domains.
AB  - To define the T-cell receptor signal transduction motif, we have transfected
      human and murine T-cell lines with a chimeric receptor consisting of the
      extracellular and transmembrane domains of human CD8 alpha and the membrane
      proximal portion of CD3 zeta containing at its C terminus either an 18-amino acid
      segment (NQLYNELNLGRREEYDVL) or alanine-scanning point mutant derivatives.
      Crosslinking of the extracellular domain of the chimera is sufficient to initiate
      Ca2+ flux, interleukin 2 production, and tyrosine phosphorylation of cellular
      proteins including the chimera. Subsequently, the chimera becomes associated with
      several tyrosine-phosphorylated proteins, among them the 70-kDa protein tyrosine
      kinase ZAP70. Mutational data identify the T-cell activation motif as
      Y(X)2L(X)7Y(X)2L and show that each of the four designated residues is necessary
      for the above activation events. Recombinant protein containing the two tandem
      SH2 domains derived from ZAP70 binds to a synthetic peptide corresponding to the
      above 18-amino acid motif but only when both tyrosines are phosphorylated; in
      contrast, little or no binding is observed to monophosphorylated or
      nonphosphorylated analogues. These results imply that after receptor crosslinking
      in T cells, and by inference also in B cells and mast cells, the motif is
      phosphorylated on both tyrosine residues, thereafter serving as a docking site
      for protein tyrosine kinases containing tandem SH2 domains.

PMID- 7517563
TI  - Membrane properties of microglial cells isolated from the leech central nervous
      system.
AB  - Membrane potentials and channel properties of microglial cells isolated from the
      leech central nervous system and maintained in culture on different substrates
      were investigated by using the patch-clamp technique. As expected, microglia on
      concanavalin A (con-A) were round and stationary, whereas those on extract of
      extracellular matrix (ECM) were spindle shaped and mobile. The mean membrane
      capacitance was 9 +/- 1 pF (s.e., n = 46), and the input resistance ranged from
      0.135 G omega to 21 G omega with a mean of 4.2 +/- 1.6 G omega (n = 19). On-cell
      patches exhibited no single-channel activity. Voltage-dependent Na+, K+ and Ca2+
      currents typical of neurons were absent. Currents evoked in response to voltage
      ramps from -100 mV to +100 mV or to steps of 4 s duration reversed in sign at or
      near 0 mV and exhibited single-channel activity of increasing amplitude for
      incrementally larger positive and negative voltage steps. No differences between
      the membrane properties of microglial cells on con-A and on ECM were evident.
      Currents were increased in fluid in which Na+ was substituted with K+, and were
      decreased when Na+ was substituted with N-methyl-D-glucamine. Varying external
      [Cl-] was without effect, as was addition to the fluid of 100 microM anthracene-9
      carboxylate, a Cl- channel blocker. Together these characteristics indicated a
      cation channel. Bath application of 100 microM serotonin reversibly increased
      both inward and outward currents as well as single-channel activity. It is
      concluded that cultured microglial cells isolated from the adult leech have high
      membrane resistance and cation channel activity influenced by serotonin.

PMID- 7517561
TI  - Paradoxical fate and biological action of peroxynitrite on human platelets.
AB  - Peroxynitrite (ONOO-), which is formed from the reaction of nitric oxide (NO) and
      superoxide (O2-), has been suggested to be responsible for some of the cytotoxic
      effects of these molecules. When protonated, ONOO- gives rise to hydroxyl (OH.)
      and nitrogen dioxide (NO2) radicals, which are capable of inducing tissue damage.
      We have investigated the effects of ONOO- on human platelets in vitro in order to
      explore the potential of this oxidant to contribute to tissue damage. ONOO-
      caused aggregation of washed platelets and reversed the inhibition of aggregation
      induced by S-nitroso-N-acetyl-DL-penicillamine (SNAP), prostacyclin, and
      indomethacin. However, in platelet-rich plasma, ONOO- not only did not possess
      proaggregatory properties but acted as an inhibitor of platelet aggregation. This
      reversal of the aggregatory effect of ONOO- could also be achieved in washed
      platelets by adding low concentrations of plasma, human serum albumin, or
      glutathione and was inhibited by hemoglobin. An analysis of the reaction products
      of ONOO- and glutathione revealed the presence of both NO and S
      nitrosoglutathione in quantities sufficient to account for the antiaggregatory
      effects observed. Thus the fate and therefore the actions of ONOO- in biological
      systems are critically dependent on the biological environment in which this
      oxidant is present.

PMID- 7517557
TI  - The low density lipoprotein receptor-related protein mediates the cellular
      degradation of tissue factor pathway inhibitor.
AB  - The low density lipoprotein receptor-related protein/alpha 2-macroglobulin
      receptor (LRP) is a cell-surface glycoprotein of 4525 amino acids that functions
      as a hepatic endocytosis receptor for several plasma proteins. These include
      alpha 2-macroglobulin-protease complexes, free plasminogen activators as well as
      plasminogen activators complexed with their inhibitors, and beta-migrating very
      low density lipoproteins complexed with either apolipoprotein E or lipoprotein
      lipase. In the current study we used human and rat hepatoma cell lines to
      demonstrate that LRP can mediate the degradation of tissue factor pathway
      inhibitor (TFPI), a Kunitz-type plasma serine protease inhibitor that regulates
      tissue factor-induced blood coagulation. The cellular degradation of 125I-labeled
      TFPI (125I-TFPI) was inhibited more than 80% both by antibodies directed against
      LRP and by the LRP-associated 39-kDa protein, a protein that inhibits the binding
      and/or cell-mediated degradation of all ligands by LRP. Using rat hepatoma cells,
      we report that at 4 degrees C, 125I-TFPI binds to approximately 2 x 10(6) sites
      per cell with an equilibrium dissociation constant of approximately 30 nM. 125I
      TFPI binding to the cell surface is not inhibited by the 39-kDa protein. Taken
      together, our results suggest that TFPI binds to an as-yet-unidentified cell
      surface molecule. After binding, LRP mediates the cellular degradation of TFPI.

PMID- 7517562
TI  - The Fanconi anemia polypeptide FACC is localized to the cytoplasm.
AB  - Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital
      anomalies, aplastic anemia, and chromosomal instability. A cDNA encoding the FA
      complementation group C (FACC) polypeptide was recently cloned [Strathdee, C. A.,
      Gavish, H., Shannon, W. R. & Buchwald, M. (1992) Nature (London) 356, 763-767].
      To further characterize this polypeptide, we generated a rabbit polyclonal
      antiserum against its carboxyl terminus. We used this antiserum to analyze the
      FACC polypeptide from normal or mutant (FA) lymphoblast cell lines. By
      immunoprecipitation, the wild-type FACC was a 60-kDa protein, consistent with its
      predicted molecular mass. FA group C cell lines expressed full-length FACC,
      truncated FACC, or no detectable FACC polypeptide. In addition, the antiserum
      specifically immunoprecipitated a 50-kDa and a 150-kDa FACC-related protein (FRP
      50 and FRP-150). Unexpectedly, cell fractionation and immunofluorescence studies
      demonstrated that the FACC polypeptide localizes to the cytoplasm. In conclusion,
      we have generated an antiserum specific for the human FACC polypeptide. The
      antiserum should be useful for screening FA cells for mutant FACC polypeptides
      and for identifying and cloning FACC-related proteins.

PMID- 7517565
TI  - From sequences to shapes and back: a case study in RNA secondary structures.
AB  - RNA folding is viewed here as a map assigning secondary structures to sequences.
      At fixed chain length the number of sequences far exceeds the number of
      structures. Frequencies of structures are highly non-uniform and follow a
      generalized form of Zipf's law: we find relatively few common and many rare ones.
      By using an algorithm for inverse folding, we show that sequences sharing the
      same structure are distributed randomly over sequence space. All common
      structures can be accessed from an arbitrary sequence by a number of mutations
      much smaller than the chain length. The sequence space is percolated by extensive
      neutral networks connecting nearest neighbours folding into identical structures.
      Implications for evolutionary adaptation and for applied molecular evolution are
      evident: finding a particular structure by mutation and selection is much simpler
      than expected and, even if catalytic activity should turn out to be sparse of RNA
      structures, it can hardly be missed by evolutionary processes.

PMID- 7517564
TI  - Ion channel gating and time interval omission: statistical inference for a two
      state Markov model.
AB  - Statistical inference is considered for a two-state Markov model of a single ion
      channel, when time interval omission is incorporated. A simple method of
      obtaining confidence sets for the mean open and closed sojourn times for the
      underlying single channel, based on the method-of-moments estimators, is
      presented. Time interval omission induces non-identifiability, in that the method
      of-moments usually leads to two distinct estimates of the mean open and closed
      sojourn times, one corresponding to the true values and the other being an
      artefact of time interval omission. A new method of overcoming such non
      identifiability on the basis of one single channel record is described. The
      methodology is illustrated by a numerical example.

PMID- 7517568
TI  - [The efficacy and rapidity of action of granulocyte colony-stimulating factor in
      a case of agranulocytosis due to noramidopyrine].

PMID- 7517571
TI  - [Chronic pancreatitis: surgical indications and treatment].

PMID- 7517566
TI  - Iloprost attenuates trauma-related pulmonary sequestration of leucocytes and
      platelets.
AB  - The purpose of this study was to investigate the effects of iloprost, a synthetic
      prostacyclin analogue, on the pulmonary cellular trapping after a standardized
      soft tissue trauma. In two groups 1 and 2 iloprost was given in doses of 100
      ng/kg/min commencing 30 and 20 min respectively prior to trauma and ceasing 10
      min after trauma. 111Indium-oxine was used to label neutrophils in 6 animals from
      each group. Platelets were labelled in 6 and 7 animals respectively. A third
      group of 11 pigs served as a control and did not receive iloprost. The pulmonary
      sequestration of platelets and neutrophils was studied dynamically with a gamma
      camera and directly after trauma was significantly less in group 1 when compared
      to the control group. A rise in pulmonary vascular resistance and pulmonary
      arterial pressure was seen in the control group immediately after trauma but this
      was not evident in the iloprost groups. PaO2 decreased significantly in group 1
      and 2 during the iloprost infusion. The results indicate that iloprost attenuates
      the pulmonary cellular sequestration and changes in central hemodynamics during
      trauma in this model.

PMID- 7517569
TI  - The effect of neutralizing monoclonal antibodies on early events in Rift Valley
      fever virus infectivity.
AB  - Monoclonal antibodies (mAb) were used to examine possible stages at which
      antibody-mediated neutralization of Rift Valley fever virus occurs, and to assess
      whether binding of antibody is dependent on viral protein structure in order that
      antibody recognition take place. Analysis of the structural properties of the
      antigenic determinants revealed that the neutralizing sites are highly
      conformation-dependent. None of the mAb prevented virus binding, suggesting that
      the epitopes they define are spatially separate from the site(s) responsible for
      virus attachment to the cellular receptor. The finding that many of the mAb also
      did not inhibit virus entry into the cell demonstrated that neutralization of
      RVFV infectivity by immune antibodies is not dependent on blocking at the early
      stages in the viral life cycle.

PMID- 7517570
TI  - Mixed-effects regression models for studying the natural history of prostate
      disease.
AB  - Although prostate cancer and benign prostatic hyperplasia are major health
      problems in U.S. men, little is known about the early stages of the natural
      history of prostate disease. A molecular biomarker called prostate specific
      antigen (PSA), together with a unique longitudinal bank of frozen serum, now
      allows a historic prospective study of changes in PSA levels for decades prior to
      the diagnosis of prostate disease. Linear mixed-effects regression models were
      used to test whether rates of change in PSA were different in men with and
      without prostate disease. In addition, since the prostate cancer cases developed
      their tumours at different (and unknown) times during their periods of follow-up,
      a piece-wise non-linear mixed-effects regression model was used to estimate the
      time when rapid increases in PSA were first observable beyond the background
      level of PSA change. These methods have a wide range of applications in
      biomedical research utilizing repeated measures data such as pharmacokinetic
      studies, crossover trials, growth and development studies, aging studies, and
      disease detection.

PMID- 7517572
TI  - [Percutaneous transluminal treatment of stenoses and obstructions in the venous
      system using vascular endoprostheses (stents)].
AB  - Benign and malignant obstructions of the superior and inferior V. cava and large
      central veins are often difficult to treat by conservative and surgical means. In
      this overview we report a new technique which keeps obstructed veins patent by
      means of percutaneously-inserted metal endoprostheses. The technique allows rapid
      and lasting relief of the clinical signs of venous inflow obstruction. The high
      clinical success rate and longterm patency of 70 to 100% in malignant stenoses,
      and close to 100% in benign obstruction, makes this technique the method of
      choice for treating superior and inferior inflow obstructions secondary to
      diseases of the V. cava and the pelvic and brachiocephalic veins. Patients
      suffering from malignancies benefit in particular from rapid improvement of their
      quality of life using an effective method with a low complication rate. Vascular
      stents may also be used in venous outflow stenosis of hemodialysis shunts.
      However, because of the high recurrence rate secondary to intimal hyperplasia,
      particularly in peripheral stenoses in the region of the arm, we recommend a
      conservative attitude. The use of stents is only indicated after one or more
      trials with conventional balloon angioplasty.

PMID- 7517567
TI  - [Progressive systemic sclerosis and cardiac arrhythmias].

PMID- 7517573
TI  - [Color Doppler flow data of breast tumors].
AB  - The recent development of high-quality colour Doppler instruments allows flow
      detection in small vessels below the resolution of B-mode imaging. Therefore,
      Doppler is now frequently used for flow detection in tumours. For breast
      examinations, CW Doppler has been in use for many years, which allows a
      sufficient definition of diagnostic criteria. Nevertheless, it is surprising that
      new studies using colour Doppler try to define different diagnostic criteria. To
      characterise the vascularity of breast lesions by colour Doppler we investigated
      127 symptomatic patients. In 54 carcinomas the average flow velocity was 32 cm/s
      and 12.6 cm/s in 73 benign conditions (p > 0.0001). Total tumour vascularisation
      was characterised by a new parameter: the sum of all flow velocities in all
      tumour vessels. In carcinomas the mean total flow as 197.9 cm/s, and 52.7 cm/s in
      benign pathologies (p > 0.0001). Mean RI (resistance index) and PI (pulsatility
      index) were calculated to describe the flow profiles. The wide variation did not
      allow for a differentiation between benign and malignant lesions.

PMID- 7517575
TI  - Beta 2-microglobulin-independent MHC class Ib molecule expressed by human
      intestinal epithelium.
AB  - A major histocompatibility complex class Ib protein, CD1d, is expressed by human
      intestinal epithelial cells (IECs) and is a ligand for CD8+ T cells. CD1d was
      found to be expressed on the surface of human IECs as a 37-kilodalton protein
      that was beta 2-microglobulin (beta 2M) independent with no N-linked
      carbohydrate. Transfection into a beta 2M- cell line confirmed that CD1d could be
      expressed at the cell surface in the absence of beta 2M. These data indicate that
      IECs use a specialized pathway for CD1d synthesis and that a beta 2M-independent
      class Ib protein may be the normal ligand for some intestinal T cells.

PMID- 7517576
TI  - The boundaries of the self and the unhealthy other: reflections on health,
      culture and AIDS.
AB  - Most accounts of the cultural stigmas associated with AIDS have not adequately
      considered the meanings through which the stigmatizing self imagines his/her
      difference from the stigmatized other. This paper argues that 'health' is a key
      concept in the fashioning of identity for the modern and contemporary middle
      class and that the 'unhealthy' come to be represented as the other of this self.
      'Healthy' and 'unhealthy,' however, must be understood both in their biomedical
      meanings and in their implicit metaphorical meanings. The 'unhealthy,'
      'contagious,' 'sexually deviant,' and 'addicted-minority' other--all condensed in
      the negative symbolism of AIDS--have become images which are mobilized as part of
      a cultural politics of reconstructing the self in conformity with intensified
      mandates for self-control. The expulsion of 'unhealthy' meanings from the self,
      an act of patrolling the borders of identity, finds its projected physical
      location in the figure of the person with HIV-AIDS.

PMID- 7517574
TI  - Homozygous human TAP peptide transporter mutation in HLA class I deficiency.
AB  - Human lymphocyte antigen (HLA) class I proteins of the major histocompatibility
      complex are largely dependent for expression on small peptides supplied to them
      by transporter associated with antigen processing (TAP) protein. An inherited
      human deficiency in the TAP transporter was identified in two siblings suffering
      from recurrent respiratory bacterial infections. The expression on the cell
      surface of class I proteins was very low, whereas that of CD1a was normal, and
      the cytotoxicity of natural killer cells was affected. In addition, CD8+ alpha
      beta T cells were present in low but significant numbers and were cytotoxic in
      the most severely affected sibling, who also showed an increase in CD4+CD8+ T
      cells and gamma delta T cells.

PMID- 7517577
TI  - Nurses' views of the coping of patients.
AB  - The findings of a study that explored the beliefs, assumptions and ideas nurses
      have about the coping of patients are presented. Interactive interviews with 26
      nurses were used to elicit explanations of the meaning of coping and stories from
      their practice that illustrated coping. Analysis of the interview transcripts
      revealed three themes in the form of idioms or particular and different ways of
      talking about coping. Each idiom represented a different perspective or view of
      coping. The first idiom represented a view of coping as a rational, cognitive
      problem-solving response to illness. The nurses attributed, and thus valued, this
      view to science. In the second idiom the nurses spoke of coping as permeated with
      values that contrasted with the prior view of coping as a rational process. In
      the final idiom the nurses spoke of coping as courage--they told stories of
      patients who had faced existential situations with strength and will. The focus
      of this idiom was on issues of spirituality, struggle, personal meaning and
      acceptance. After each idiom is delineated and illustrated by data, the
      discussion is concentrated on the orientational and ontological metaphors that
      underlie them. Interpretation of the origin and construction of these different
      ways of talking about coping, and their underlying metaphorical meanings, is made
      in the context of cultural and subcultural influences.

PMID- 7517578
TI  - Serologic diagnosis of viral hepatitis.
AB  - Recent advances have made available to the clinician multiple serologic tests for
      the diagnosis and evaluation of acute and chronic viral hepatitis. While the
      multiplicity of tests available can be confusing, selective use of these
      serologic tests tailored to the clinical situation can be of great value in
      identifying the agent causing the liver disease. I present a clinically oriented
      discussion of the serologic tests available to diagnose viral hepatitis.

PMID- 7517579
TI  - Sclerotherapy for malignant pleural effusions: alternatives to tetracycline.
AB  - Malignant pleural effusion (MPE) causes significant morbidity in cancer patients.
      Management is often challenging because of the recurrent nature of MPE and the
      inconsistent response rates of various treatments. In patients whose underlying
      malignancy is unresponsive to systemic chemotherapy or radiation, MPE is usually
      managed by tube thoracostomy with subsequent sclerotherapy. Selection of a
      sclerosing agent should be based on several factors, including efficacy,
      toxicity, cost, and convenience. Of the numerous agents available for managing
      MPE, doxycycline, bleomycin, and talc have emerged as the most promising. Even
      these agents have disadvantages, such as the high cost of bleomycin and the
      possible need for multiple dosing of doxycycline. Talc is clearly the most
      controversial of the three. Although its efficacy is well documented, its role
      remains unclear because of its unattractive side effect profile and inconvenient
      preparation and administration. Results of controlled comparative trials are
      needed to identify the optimal sclerosing agent.

PMID- 7517580
TI  - Prostate-specific antigen and digital rectal examination in screening for
      prostate cancer: a community-based study.
AB  - In this study, 1,027 healthy men over age 40 were screened for prostate cancer
      with digital rectal examinations (DRE) and prostate-specific antigen (PSA)
      levels. Findings were abnormal in 189 (18%). PSA levels alone were abnormal (>
      4.0 ng/mL) in 111 men (12%), 60 men (8%) had abnormal DRE and normal PSA, and 18
      men had abnormal results of both examinations. Of the 189 men, 176 (93%) were
      referred for follow-up studies, and 39 cases of prostate cancer were detected. Of
      the 60 men with abnormal findings on DRE and normal PSA levels, only 2 men (3%)
      were found to have prostate cancer. Twenty-two of the 107 men (21%) with PSA
      levels between 4.0 and 9.9 ng/mL and 14 of 22 men (64%) with a PSA level greater
      than 10 ng/mL had prostate cancer. Conversely, 36 of the 39 men (92%) with
      prostate cancer had a PSA level greater than 4.0 ng/mL. Of 18 men with both
      abnormal DRE and elevated PSA, 9 (50%) were found to have prostate cancer.
      Overall, the 39 men found to have prostate cancer constituted 3.8% of the
      population screened; 25 of them (64%) had disease clinically confined to the
      prostate. PSA in combination with DRE appears to be useful in detecting prostate
      cancer in its early stages. Prospective randomized trials must be completed to
      determine whether early detection will have an impact on overall mortality from
      prostate cancer.

PMID- 7517581
TI  - Pathology of BPH.
AB  - Much research has been conducted to determine which tissue (epithelium or stroma)
      in the prostate gives rise to benign prostatic hyperplasia (BPH). Considering
      that BPH displays two structural compartments, stromal and epithelial and that
      the periurethral and transitional regions are particularly involved, the
      immunohistochemical and regional evaluation of steroid receptors concentration, 5
      alpha reductase, DHT and estrogen activity, may show important data on the role
      of these factors in BPH development. We started a immunohistochemical study on
      the epidermal growth factor (EGF) concentrations in the periurethral, central and
      pericapsular zones of BPH samples, considering the stroma-epithelium ratio;
      investigations are performed on BPH patients submitted to transvesical
      prostatectomy. Considering that the periurethral zone is particularly involved in
      BPH, the presence of high concentration of growth factors in this region, may
      support the concept of their involvement in BPH.

PMID- 7517582
TI  - Plant extracts in BPH.
AB  - In Italy plant extracts represent 8.6% of all pharmacological prescriptions for
      Benign Prostatic Hyperplasia (data from 1991). This review evaluates all the
      suggested mechanisms of action for plant extracts. Recently we demonstrated an
      antiestrogenic effect of Serenoa Repens in BPH patients. Clinical trials with
      plant extracts have yielded conflicting results. In a recent review by Dreikorn
      and Richter, only five placebo controlled studies were found. Moreover, as
      opposed to chemically defined drugs, it is possible that for these extracts the
      active ingredients are not known; consequently pharmacodynamic and
      pharmacokinetic data are often missing. The International Consultation of Benign
      Prostatic Hyperplasia (Paris, June 1991) concluded that, to date,
      phytotherapeutic agents must be considered as a symptomatic treatment. Now more
      adequate pharmacological and clinical studies, placebo controlled, should
      determine the exact role of these drugs in the treatment of BPH.

PMID- 7517583
TI  - [Bladder instability in the elderly patient with obstructive prostatic
      hypertrophy: comparative urodynamic study using non-obstructed women of the same
      age].
AB  - 62 men with prostatic hypertrophy and bladder obstruction and 31 age matched
      women without lower urinary tract obstruction, underwent urodynamic testing which
      included uroflowmetry, gas cystometry, urethral pressure measurement:
      electromyography and pressure flow study was only performed to the patients with
      prostatic hypertrophy. No patient with neurological disease, diabetes mellitus,
      pelvic operation, neoplasm or stone of the bladder was admitted to the study.
      Involuntary detrusor contractions (unstable detrusor) were found in 74.2% of male
      patients and in 25.8% of female patients. In male patients aged over 72 the
      percentage was 81.8% while in the female patients of the same age was 60%. All
      the 62 male patients underwent prostatectomy. Two months after surgery,
      acystometry was done. Unstable detrusor was found in 63.1% of cases. Patients
      over 80 had a percentage of 100%. These data suggest obstructive prostatic
      hypertrophy as an important factor in development of involuntary bladder
      contractions, but the primary pathophysiological factor appears to be age of
      patients.

PMID- 7517584
TI  - HLA-B67: a member of the HLA-B16 family that expresses the ME1 epitope.
AB  - HLA-B67 is an uncommon antigen that has been defined by serological
      crossreactivity with the HLA-B7 and HLA-B16 (B38 and B39) antigens. It is found
      at highest frequency in certain Oriental populations and has been best defined in
      the Japanese. Nucleotide sequencing of cDNA encoding B67 reveals the B*6701
      allele to be a subtype of B39 which differs from B*39011 by substitution at
      residues 67-71 of the alpha 1 helix. In the region of difference B*6701 is
      identical in sequence to B7, B22, B27 and related molecules that express the
      epitope recognized by the ME1 monoclonal antibody. That the HLA-B67 molecule
      binds strongly to the ME1 antibody was demonstrated by immunoprecipitation and
      cell surface binding assays. Identical B*6701 nucleotide sequences were obtained
      for the B67 alleles isolated from 2 unrelated Japanese and 1 North American
      caucasoid.

PMID- 7517585
TI  - Behavior of embryonic chick heart cells in culture. 3. Spatial distribution of
      epidermal growth factor in heart muscle cells.
AB  - Muscle cell-enriched primary cell cultures were prepared from 8-day embryonic
      chick heart ventricles. Immunostaining with an anti-EGF antibody detected the
      presence of EGF in the heart muscle cells, in a perinuclear distribution. In
      addition, some of the EGF appeared to be associated with the sarcomeres.
      Moreover, immunostaining with an anti-EGF receptor antibody also detected
      perinuclear localization, albeit not among the sarcomeres. Previous studies have
      shown that the heart muscle and non-muscle cells in culture respond to EGF to
      increase [3H]thymidine incorporation and cell division (Lau, 1993b). These data
      suggest the roles of EGF as a natural regulator in the development of the
      embryonic chick heart.

PMID- 7517587
TI  - Oxygen-sensitive ion channels: how ubiquitous are they?

PMID- 7517586
TI  - Aprotinin efficacy on intraoperative bleeding and transfusion requirements in
      orthotopic liver transplantation.
AB  - BACKGROUND: Bleeding complications frequently occur during orthotopic liver
      transplantation (OLT), particularly in patients with liver cirrhosis. Enhanced
      fibrinolytic activity in plasma was seen to play a key role in the development of
      the hemostatic disorder and of hemorrhages. Aprotinin, a serine protease
      inhibitor, has been used in the prevention and/or treatment of hyperfibrinolytic
      states. STUDY DESIGN AND METHODS: In the present study, the effect of aprotinin
      on bleeding complications and transfusion requirements was investigated in OLT
      patients with liver cirrhosis. Seven consecutive cirrhotic patients undergoing
      OLT were infused with aprotinin following an original protocol (1,000,000-KIU
      intravenous loading dose plus 500,000 kallikrein-inhibitory units per hour until
      skin closure). Seven previous cirrhotic OLT patients not receiving aprotinin were
      used as controls. RESULTS: In the treated group, a significant decrease in the
      number of transfused units of packed red cells (48.7%, p < 0.01), fresh-frozen
      plasma (24.4%, p < 0.05), platelets (35.9%, p < 0.01), and autologous blood
      (55.2%, p < 0.01) was observed as compared with the control group. Moreover, the
      mean length of operation was significantly shorter in the aprotinin-infused
      patients than in untreated patients (8.3 +/- 1.2 vs. 10.1 +/- 1.8 hours,
      respectively; p < 0.01)). In the aprotinin-treated group, the antifibrinolytic
      efficacy was confirmed by the lack of increase in D-dimer levels and decrease of
      fibrinogen in plasma; on the contrary, these changes were always seen in the
      group not receiving aprotinin. CONCLUSION: Infusion of aprotinin during OLT in
      cirrhotic patients can be recommended for the prevention of hyperfibrinolysis
      triggered bleeding, thus reducing transfusion requirements. A possible protective
      effect on the primary nonfunction of the grafted liver is suggested.

PMID- 7517589
TI  - Brain injury in a dish: a model for reactive gliosis.
AB  - Reactive gliosis is a powerful response to brain injury and subsequent neuronal
      damage in vivo. Neuronal cell cultures are now well established as assays to
      study this process in vitro. However, equivalent studies of purified glial cell
      populations have only recently been achieved, following the realization that
      glial cells produce many of the neuropeptides, transmitters and growth factors
      that are produced also by neurons. There is now scope for studies in vitro that
      use mixed, identified populations of glial and neuronal cells to dissect the
      interactions between the two. Such cultures also lend themselves to assays for
      potential therapeutic strategies for brain injury that take account of all the
      different cell types found in the brain.

PMID- 7517588
TI  - CNS stress response: too hot to handle?

PMID- 7517590
TI  - Tools for investigating functional interactions between ligands and G-protein
      coupled receptors.
AB  - A general assay for evaluating functional interactions between ligands and G
      protein-coupled receptors within minutes has been developed. The system uses the
      principles employed by animals such as reptiles, amphibians and fish to control
      their colors. In nature, activation of G-protein-coupled receptors expressed by
      skin cells called chromatophores effects pigment redistribution within the cells
      to change an animal's coloration. The in vitro 'chameleon in a dish' equivalent
      can use essentially any cloned G-protein-coupled receptor.

PMID- 7517591
TI  - Conductance injection.

PMID- 7517593
TI  - Neurotransmission--the link integrating Alzheimer research?

PMID- 7517592
TI  - The puzzle of PrPSc and infectivity--do the pieces fit?

PMID- 7517595
TI  - Na(+)-activated K+ channels: a new family of large-conductance ion channels.
AB  - Sodium-activated K+ channels (IK(Na)) are a class of large-conductance ion
      channels expressed in several populations of vertebrate neurons, mammalian
      cardiac myocytes and Xenopus oocytes. These channels are activated by the binding
      of Na+ to sites located on the cytoplasmic face of the channel. The physiological
      functions of IK(Na) channels have been difficult to ascertain, in part because
      their activation typically requires Na+ concentrations considerably higher than
      those that are normally present in the cytosol. However, there is now evidence
      suggesting that IK(Na) can play a role in the regulation of neuronal
      excitability, the modulation of the action-potential waveform, and the responses
      of excitable cells to hypoxia and ischemia.

PMID- 7517596
TI  - Dendritic attenuation of synaptic potentials and currents: the role of passive
      membrane properties.
AB  - The dendritic trees of neurons are structurally and functionally complex
      integrative units receiving thousands of synaptic inputs that have excitatory and
      inhibitory, fast and slow, and electrical and biochemical effects. The pattern of
      activation of these synaptic inputs determines if the neuron will fire an action
      potential at any given point in time and how it will respond to similar inputs in
      the future. Two critical factors affect the integrative function of dendrites:
      the distribution of voltage-gated ion channels in the dendritic tree and the
      passive electrical properties, or 'electrotonic structure', upon which these
      active channels are superimposed. The authors review recent data from patch-clamp
      recordings that provide new estimates of the passive membrane properties of
      hippocampal neurons, and show, with examples, how these properties affect the
      shaping and attenuation of synaptic potentials as they propagate in the
      dendrites, as well as how they affect the measurement of current from synapses
      located in the dendrites. Voltage-gated channels might influence the measurement
      of 'passive' membrane properties and, reciprocally, passive membrane properties
      might affect the activation of voltage-gated channels in dendrites.

PMID- 7517598
TI  - Reduced cavitation-induced cellular damage by the antioxidative effect of vitamin
      E.
AB  - Fragmentation of human urinary and biliary stones by shock waves in
      extracorporeal lithotripsy is accompanied by tissue damage. Both the
      fragmentation as well as the side effects are often attributed to cavitation. The
      hazardous potential of cavitation is not only of a physical nature but also of a
      chemical nature, because of the generation of free radicals, e.g. .OH, .H and
      .O2. After the application of shock waves, we have demonstrated cavitation
      generated free radicals in cell-free solutions and also in the surviving and
      intact suspended MGH-U1 cells by hydroethidine measurements. Under electron
      microscopical inspection, the same cells exhibited perinuclear cisternae, damaged
      mitochondria and numerous intracellular vacuoles. The contribution of free
      radicals to cell damage was investigated by reducing the vitamin E level in rats
      by a tocopherol free diet and by incubating L1210 cells in a tocopherol enriched
      medium. After 250 shock waves, ex vivo erythrocytes revealed a 75% increase in
      total cell disruption over cells from non-depleted rats. The in vitro experiments
      with L1210 cells exhibited a moderate protection by the addition of this
      scavenger of free radicals.

PMID- 7517597
TI  - Processing of information from different sources: spatial synaptic integration in
      the dendrites of vertebrate CNS neurons.
AB  - Most synapses on a neuron are distributed along the dendrites. Inputs from
      different types of presynaptic neurons often distribute to different dendritic
      compartments. This provides an anatomical framework for spatial synaptic
      integration. At the same time, a plethora of time- and voltage-dependent
      responses are present, usually with a distinct distribution over the somato
      dendritic membrane. These intrinsic conductances shape the local dendritic
      response to ligand-gated conductances, and provide the dendrites with a dynamic
      way of regulating the interaction between synapses. Recent results from neurons
      in the vertebrate CNS exemplify these mechanisms of dendritic integration.

PMID- 7517594
TI  - Neurotoxins: overview of an emerging research technology.
AB  - Neurotoxins have highly specific actions on molecular targets, and thus offer an
      effective means of characterizing the growing number of identified ion channels
      and receptors in the nervous system. This article and the Neurotoxins Supplement
      accompanying this issue of TINS provide a convenient reference source to
      facilitate the use of toxins as selective, diagnostic ligands in research.
      However, while many toxins exert potent actions on target receptors, it must be
      emphasized that their effects can be complex, and certain general pitfalls often
      become apparent. Some examples will be given illustrating these complexities and
      their impact on experimental interpretation. In addition, the potential for the
      purposeful creation of new 'designer' toxins using molecular cloning will also be
      addressed.

PMID- 7517599
TI  - Interferon.

PMID- 7517600
TI  - Recent developments in the treatment of human papillomavirus.

PMID- 7517601
TI  - [The value of sequential CD 34 measurement for carrying out stem cell pheresis].
AB  - The recent significant improvement in disease-free survival in patients with
      certain haematological malignancies is due to high-dose chemotherapy and
      subsequent autologous bone marrow and/or stem cell transplantation. The
      proliferation and egression of stem cells into the peripheral blood must first be
      stimulated by defined chemotherapy and/or by administration of cytokines.
      However, the increase of circulating stem cells in peripheral blood is limited to
      only a few days. By immunologically analysing white blood cells for the
      expression of the surface antigen CD 34 it is possible to calculate the numbers
      of haematopoietic progenitor cells. Thus, besides monitoring haematopoietic
      recovery, the estimation of CD34+ cells in the peripheral blood can be used to
      indicate the optimal time point for stem cell collection. Two to four stem cell
      pheresis (one per day) may then yield sufficient stem cells to enable the safe
      and rapid reconstitution of haematopoiesis following supralethal chemotherapy.

PMID- 7517602
TI  - Immunogenicity of a mycobacterial T-cell epitope expressed in outer membrane
      protein PhoE of Escherichia coli.
AB  - The outer membrane protein PhoE of Escherichia coli can be used for the
      expression of foreign antigenic determinants. Previously, a T-cell epitope of the
      65 kDa heat shock protein (hsp65) of Mycobacterium tuberculosis, comprising amino
      acids 180 to 188, was expressed in PhoE. The hybrid protein induced proliferation
      of epitope-specific T-cell clones in vitro. In this report, the potential of the
      hybrid protein to induce an in vivo T-cell response against the 180-188 T-cell
      epitope was assessed. Popliteal lymph node cells, isolated from rats immunized
      with PhoE containing the hsp65 epitope, showed high proliferative responses to a
      synthetic peptide consisting of amino acids 180 to 188 of hsp65, indicating that
      the epitope is immunogenic in the PhoE-associated conformation.

PMID- 7517603
TI  - Termination of pregnancy in mice following administration of antibodies to the
      pentadecapeptide 10-24 of chicken riboflavin carrier protein: identification of a
      bioneutralizing epitope of chicken riboflavin carrier protein.
AB  - Our studies have shown that the administration of antibodies to chicken
      riboflavin carrier protein (cRCP) or disulfide-reduced carboxymethylated cRCP
      (RCM-RCP) leads to termination of pregnancy in mice. In an attempt to delineate
      the bioneutralizing epitopes, a combination of chemical modification and
      predictive methods was used. The results led to the identification of the region
      10-24 of cRCP as a potential candidate. A single injection of antipeptide
      antibodies to pregnant mice on day 11 resulted in 100% pregnancy termination.
      This was accompanied by a drastic reduction in circulatory progesterone as early
      as 24 h after the antibody administration. These results thus demonstrate that
      the amino acid sequence 10-24 of cRCP harbours a bioneutralizing epitope of cRCP.

PMID- 7517604
TI  - [Effect of hypoxia on nitric oxide formation and leukotriene metabolism in the
      perfused rat liver].
AB  - Endotoxinaemia stimulates the generation of cysteinyl leukotrienes (LT), potent
      mediators of inflammation which are preferentially eliminated into the bile.
      Nitric oxide (NO) is a mediator molecule that has a possible protective role in
      liver injury. As sepsis and shock often lead to the development of hypoxic
      regions in the liver, the influence of hypoxia on the metabolism of cysteinyl
      leukotrienes and the hepatic production of NO were investigated in the isolated
      perfused rat liver. Livers were perfused in a non-recirculating haemoglobin-free
      system from the portal to the caval vein. Perfusion medium was equilibrated with
      95% O2/5% CO2. In hypoxia experiments, gassing was changed to 95% N2/5% CO2 for
      20 min. Tritiated leukotrienes were infused to the portal vein and metabolites in
      effluent and bile were measured by HPLC. Hypoxia did not influence the uptake of
      3H-LTC4 and 3H-LTE4 but biliary elimination was reduced by 50-60% compared to
      normoxic control experiments. In hypoxia, the metabolite pattern in bile was also
      significantly changed with a decrease of omega-oxidation products. Following
      reoxygenation larger amounts of leukotrienes were excreted from the liver into
      the bile. To induce NO synthase in the liver, rats were injected
      intraperitoneally with endotoxin 6 hours before livers were isolated for
      perfusion. In contrast to nontreated livers, nitrite and nitrate, the oxidation
      products of NO, were detectable in the effluent perfusate. Basal NO2(-)+NO3-
      release was 5.3 (1.2) nmol/g liver/min. NO2(-)+NO3- release was stimulated by L
      arginine infusion, whereas hypoxia resulted in an almost complete
      inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517605
TI  - [An immunocytochemical study of neuropeptide-like in a ciliated protozoan,
      Stylonychia mytilus].
AB  - An immunocytochemical investigation with both B-SA and ABC methods, under LM and
      EM, was carried out on Stylonychia mytilus by using 7 antisera to vertebrate
      neuropeptides, hormones and TH. The immunotests showed the presence of substance
      p-, neuropeptide y-, cck-8-, somatostatin-, beta-endorphin, adrenocorticotropic
      hormone-, and TH-like immunoreactive molecules in Stylonychia mytilus. The
      distributions of these immunoreactive substances in Stylonychia mytilus were
      described.

PMID- 7517606
TI  - Granulocyte colony-stimulating factor for neutropenia secondary to ticlopidine.

PMID- 7517607
TI  - Peripheral blood B lymphocytes in multiple myeloma.
AB  - Multiple myeloma (MM) is a disease of terminally differentiated B lineage cells
      and thus alterations in circulating B cells may be anticipated. We studied
      peripheral blood B cells by flow cytometry in 45 untreated MM patients and
      compared the results to 25 age-matched controls. The total lymphocyte count and
      the absolute number and percentage of CD20+ cells were significantly decreased in
      MM patients. Analysis of the relative amounts of CD20+ cells expressing surface
      immunoglobulin kappa or lambda light chain isotype did not show either clonal B
      cell excess or light chain isotype suppression. The percentages of CD10+ and
      CD20+10+ cells were low both in MM patients and in controls. We consider that the
      CD20+ cells analysed in this study mainly consisted of normal polyclonal B cells.
      However, the percentage of the CD20+ cells in the peripheral blood of MM patients
      was a prognostic factor for survival, both as a continuous and as a dichotomized
      variable.

PMID- 7517609
TI  - Histochemical aspects of calcium regulation by the enamel forming cells during
      matrix formation and maturation.

PMID- 7517608
TI  - Transverse nail ridgings (Beau's lines) induced by chemotherapy.
AB  - Transverse grooves of the nails, designated as Beau's lines, were observed in a
      patient with malignant lymphoma given chemotherapy. Beau's lines disappeared in
      the treatment-free intervals. This observation supports the concept that these
      lines are the result of the suppressed growth of the nail matrix caused by
      antimitotic drugs.

PMID- 7517612
TI  - Interferons in the treatment of advanced breast cancer.
AB  - In the past two decades interferons have undergone extensive phase I and II
      evaluations in various types of cancers, including breast cancer. This article
      reviews the experience, obtained from preclinical and clinical studies, about the
      clinical rationale efficacy and toxicity of interferons in cancer treatment. In
      particular, we examine the preclinical experience in which antineoplastic
      activity of interferon against breast cancer has been demonstrated. Finally we
      discuss clinical data accumulated using interferon-alpha, interferon-beta and
      lymphoblastoid interferon alone or in combination in metastatic breast cancer
      patients. The use of the interferons in the treatment of breast cancer remains
      investigational and the optimal scheduling undetermined. New methods of
      administration may maximize the antitumor effects in order to better understand
      the role of interferon in clinical oncology.

PMID- 7517610
TI  - A new computer analysis technique using automatic threshold selection algorithm,
      available for quantitative estimation of the immunostained dendrites of the
      cerebellum.
AB  - We developed a new computer image analysis technique with application of an
      automatic threshold selection (ATS) algorithm which was successfully used in the
      quantitative evaluation of a highly complex texture of immunostained brain
      tissue. We applied this new method for estimation of the volume of the Purkinje
      dendrites, which were immunohistochemically stained for inositol 1,4,5
      trisphosphate receptor protein (P400), and demonstrated a significant reduction
      of the dendritic arborization of the Purkinje cells of a neurological mutant
      mouse. Wriggle mouse Sagami, which would appear normal if stained with
      conventional methods such as H-E and Nissle staining.

PMID- 7517611
TI  - Symptoms in schizophrenic syndromes in relation to age, sex, duration of illness
      and number of previous hospitalizations.
AB  - In studies by means of the Swedish version of the Positive and Negative Syndrome
      Scale, we have demonstrated a 5-factor model of schizophrenia, including
      positive, negative, excited, anxious/depressive and cognitive factors. In this
      study, the 5 factors were correlated with background factors in a series
      comprising 140 patients with schizophrenic syndromes. None of the 5 factors
      revealed any significant age or sex differences. The positive factor correlated
      positively with the number of previous hospitalizations and the negative factor
      correlated negatively. The excited factor correlated negatively with age at
      onset, age at first hospitalization and positively with the duration of the
      illness and the number of previous hospitalizations. The cognitive factor
      correlated negatively with age at onset and age at first hospitalization and
      positively with the duration of the illness. Age at onset was positively
      correlated with delusions, excitement, unusual thought content and poor impulse
      control and negatively with lack of spontaneity. The duration of illness
      correlated positively with excitement, difficulty in abstract thinking and
      mannerisms. The number of previous hospitalizations correlated positively with
      delusions, excitement, unusual thought content and poor impulse control and
      significant negative correlations were demonstrated as concerns blunted affect
      and lack of spontaneity.

PMID- 7517613
TI  - Absence of transsynaptic transport in cerebello-thalamo-cortical path of the rat.
AB  - Attempts to visualize the cerebello-thalamo-cortical path in the rat were made
      with different approaches. We tried (1) double labelling with somatopetal tracing
      from the motor cortex and somatofugal from the cerebellar nuclei, (2)
      transmembrane labelling by depositing biocytin or wheat germ agglutinin (WGA)
      into the motor cortex or cerebellum. WGA was either iodinated with 125I or
      conjugated with horseradish peroxidase (HRP). The double labelling technique
      showed an overlap of the tracers in the same thalamic region but no evidence of
      transsynaptic transport in either direction was obtained. Our results indicate a
      difference in the organization of this system in primates and rodents, since
      transsynaptic labelling in the cerebellar nuclei after injections of WGA-HRP
      conjugate in the monkey motor cortex has been found.

PMID- 7517614
TI  - Differential response of microtubule-associated protein 2 (MAP-2) in rat
      hippocampus after exposure to trimethyltin (TMT): an immunocytochemical study.
AB  - Several neurotoxins induce changes in microtubule-associated protein 2 (MAP-2),
      the cytoskeletal protein primarily and highly enriched in the dendritic
      compartment of neurones. The present study aimed to investigate the fate of MAP-2
      after administration of trimethyltin (TMT), an environmental neurotoxin. An
      immunocytochemical staining was performed in the hippocampus, known to be the
      most vulnerable brain region after TMT exposure. Prolonged survival time (21
      days) following i.p. injection of a single dose of TMT (8 mg/kg) led to a
      considerable changes in intensity and pattern of distribution of MAP-2
      immunoreactivity within the structure. A significant decrease in the staining was
      observed in the hippocampus proper especially in CA4/CA3 and CA1 subfields. This
      decrease was correlated with the severity in pyramidal cell loss previously
      reported by others. On the contrary, an increased density of MAP-2 immunostained
      dendrites was found in the molecular layer of dentate gyrus. Since TMT has been
      recognized as an agent damaging not only the hippocampus but also other limbic
      structures, the latter result might be interpreted in terms of postsynaptic
      changes due to hippocampal deafferentation.

PMID- 7517615
TI  - Allergen-induced airway responses in rats pretreated with Sephadex.
AB  - Even though the eosinophil is potentially an important contributor to airway
      narrowing during the late allergic airway response, direct evidence of its
      participation is lacking. Therefore, we examined the effects of eosinophilia
      induced by Sephadex on the magnitude of the late airway response of sensitized
      rats following allergen challenge. Brown Norway rats were actively sensitized to
      ovalbumin (OA). At the same time and 14 days later, a test group was administered
      Sephadex G200 (0.5 mg intravenously). The animals were challenged with an aerosol
      of OA and pulmonary resistance (RL) was measured over 6 h. The early response to
      OA reached a peak more rapidly and the magnitude of the late response, measured
      as the area under the curve of RL against time, was significantly greater in the
      Sephadex-treated group (48.3; geometric mean) compared to the control animals
      (18.9; p < 0.02). The percentage of eosinophils was increased in the
      bronchoalveolar lavage of Sephadex-treated animals (4%) compared to the controls
      (0.9%; p < 0.02) following OA challenge. These results demonstrate that Sephadex
      induces eosinophilia in Brown Norway rats and is associated with an increase in
      the late allergic airway response. This is consistent with the hypothesis that
      the eosinophil is an important determinant of the late response.

PMID- 7517618
TI  - Isolation and identification of Cryptosporidium parvum oocysts with continuous
      Percoll gradients and combined alcian blue-giemsa staining.

PMID- 7517619
TI  - [Experience of a double Malecot polyurethane intraurethral catheter in patients
      with dysuria].
AB  - We reviewed our experience of using double Malecot polyurethane intraurethral
      catheters (IUC). Ten patients with dysuria were treated between April 1991 and
      April 1993. Seven patients with benign prostatic hypertrophy (BPH) were judged as
      in a high risk group for operation. The three other patients had neurogenic
      bladder (two had underactive bladder and 1 had overactive bladder). Under local
      anesthesia, 150 ml of 0.1% Povidone iodine solution was infused into the bladder
      through a Nelaton catheter. Under guidance by ultrasonography, an IUC was placed
      into the bladder neck and posterior urethra using the specially designed
      introduction set. An long-term follow up of the BPH patients, two IUCs were
      removed for operation and one was exchanged for an indwelling catheter because of
      deterioration in general condition. In the neurogenic bladder patients, all IUC
      were removed because of the increase of residual urine, formation of a
      pseudourethra, or dislocation into the bladder. Side effects were observed in 6
      patients such as, urethral bleeding and stone formation in the stent. Erosion and
      bleeding tendency in the urethral mucosa were shown in the prolonged duration
      cases. We conclude that a urethral stent is an effective devise for a high risk
      patient with benign prostatic hypertrophy but we must keep each patient under
      strict observation for complications during IUC placement.

PMID- 7517620
TI  - [Dynamic study of the hormonal levels and tumor markers after the first
      administration of long-acting LH-RH analogue in patients with prostate cancer].
AB  - The dynamics of hormonal levels and tumor markers after the first administration
      of long-acting luteinizing hormone-releasing hormone (LH-RH) analogue were
      evaluated in patients with prostate cancer. Eight patients with
      histopathologically proved prostate cancer who were previously untreated were
      studied. The surge in plasma testosterone was recognized in 7 patients after the
      first administration of a long-acting LH-RH analogue, and reached the highest
      level after the 3rd day in 6 patients and 14th day in 1 patient. The onset of
      flare-up reaction due to a transient increase in plasma testosterone was
      recognized in 3 patients, whose clinical symptoms and signs were increased bone
      pain in 2 patients and acute urinary retention in 1 patient. An abnormal level of
      serum prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) was
      observed in 7 of the 8 patients before treatment. The serum PAP and PSA levels
      slightly increased after treatment in 4 and 3 patients, respectively. These
      findings suggest that the combination of estrogen or antiandrogen would allow a
      safer use of long-acting LH-RH analogue to prevent the risk of a flare-up
      reaction associated with the first administration of long-acting LH-RH analogue.

PMID- 7517616
TI  - S35b, a new phenylsulfonylfuroxan compound, inhibits thrombin-induced synthesis
      of platelet-activating factor and prostacyclin in human endothelial cells.
AB  - Endothelial cells (EC) produce platelet activating factor (PAF) and prostacyclin
      (PGI2) in response to inflammatory agents such as thrombin. Upon cell stimulation
      a calcium-dependent phospholipase A2 (PLA2) is activated which hydrolyzes a
      membrane phospholipid to yield 1-0-alkyl-2-lyso-sn-glycero-3-phospho-choline
      (lyso-PAF) and free arachidonic acid. Lyso-PAF is in turn converted into PAF by a
      specific acetyltransferase and arachidonic acid is metabolized via cyclic
      endoperoxides to PGI2. In the present study we report that S35b (4-methyl-3
      phenylsulfonylfuroxan), a new phenyl-sulfonylfuroxan compound with potent
      antiaggregatory effect, inhibits thrombin-induced PAF synthesis and
      acetyltransferase activation as well as PGI2 production in human umbilical vein
      endothelial cells (HUVEC) in a concentration-dependent way. Additionally, we show
      that S35b stimulates the production of cyclic GMP (cGMP) in HUVEC in a
      concentration- and time-dependent manner. At high concentration, S35b potentiates
      the cAMP increase induced by iloprost or forskolin without having a significant
      influence on cAMP level itself. Potentiation of cAMP increase during agonist
      induced EC stimulation seems not to be important for the effect of S35b on
      cellular function as the compound is active in inhibiting PAF production when
      endothelial cells are pretreated with indomethacin to block PGI2 synthesis. The
      increase of cGMP evoked by S35b may account for the effect on endothelial cell
      function.

PMID- 7517621
TI  - [Concentrations of new quinolone agents in serum and prostate tissue].
AB  - Twenty five patients with benign prostate hypertrophy were administered ofloxacin
      (OFLX) simultaneously with norfloxacin (NFLX) in 6 patients, ciprofloxacin (CPFX)
      in 10, tosfloxacin (TFLX) in 5 and enoxacin (ENX) in 4 patients. The dose of
      these new quinolones was 100 mg (except 150 mg of TFLX). Their concentrations in
      the serum and the prostate tissue were measured by high performance liquid
      chromatography (HPLC). The serum concentration of OFLX was significantly higher
      than that of NFLX, CPFX, TFLX or ENX. The prostate tissue concentration of OFLX
      was significantly higher than that of CPFX or TFLX. The ratio of tissue versus
      serum concentration of each new quinolone agent was not significantly different.
      The high OFLX tissue concentration appeared to be caused by the high serum
      concentration.

PMID- 7517622
TI  - [Adrenal hepatoid carcinoma producing alpha-fetoprotein: a case report].
AB  - A case of left adrenal hepatoid carcinoma is reported. The patient was a 57-year
      old male and his chief complaint was general fatigue. Preoperative laboratory
      data showed markedly increased levels of alpha-fetoprotein (AFP) (30,500 ng/ml)
      and PIVKA-II (3.01 AU/ml). Both computed tomography (CT) and magnetic resonance
      computed tomography (MRCT) showed left adrenal tumor (8 x 5 cm). Angiography
      showed hypervascular tumor over the upper pole of the left kidney.
      Thoracoabdominal nephro-adrenalectomy was performed. Histological examination
      demonstrated hepatoid carcinoma of the left adrenal gland. AFP was positive in
      the tumor cells. The levels of both AFP and PIVKA-II dropped to the normal range
      postoperatively. Hepatoid carcinoma in the urological field is very rare. As
      hepatoid carcinoma in the Japanese literature in the urological field, there were
      only 4 cases of renal tumor, 2 cases of renal pelvic tumor, 2 cases of
      retroperitoneal space and 1 case of urachal tumor. This is the first report of
      adrenal hepatoid carcinoma in Japan.

PMID- 7517617
TI  - NK1 receptors mediate tachykinin-induced plasma extravasation in the rat knee
      joint.
AB  - The tachykinin receptor type that mediates tachykinin-induced plasma
      extravasation in the rat knee joint was identified by using selective antagonists
      as well as natural or synthetic agonists. Substance P (SP) and neurokinin (NK) A
      induced plasma extravasation with almost the same potency and the maximum
      response was obtained at 5 nmol/knee. NKB was about ten times less potent than SP
      or NKA. The NK1 selective agonist, [Sar9, Met(O2)11]-SP, was about ten times more
      potent than SP, and the NK2 selective agonist, [Nle10]-NKA4-10, was about fifty
      times less potent than NK1 agonist. The NK3 agonist, Senktide, was totally
      ineffective at 0.5-50 nmol/knee. All responses induced by SP (5 nmol/knee), NKA
      (5 nmol/knee), NKB (50 nmol/knee), NK1 agonist (0.5 nmol/knee) or NK2 agonist (25
      nmol/knee) were significantly and profoundly inhibited by the NK1 selective
      antagonist, RP67580, but not by the NK2 selective antagonist, SR48968. Taken
      together, we conclude that tachykinin-induced plasma extravasation in the rat
      knee joint is mediated via NK1 receptors.

PMID- 7517623
TI  - [Transurethral hyperthermic treatment in patients with benign prostatic
      hypertrophy].
AB  - Transurethral hyperthermic treatment was performed on 30 patients with benign
      prostatic hypertrophy (BPH). Two patients had a urethral catheter because of
      urinary retention. The prostate was heated transurethrally. The treatment
      consisted of 3-8 sessions of 60 min. each. To evaluate this treatment, the
      following parameters were determined before and 1-5 weeks after the last
      hyperthermia session; subjective symptoms score, and as objective data residual
      urine volume and uroflowmetry. The symptoms score improved in 25 (83%) patients.
      Of 2 patients with a catheter, the catheter could be removed from 1 patient.
      Although there was no change in prostatic volume, significant decreases in
      residual urine volume, and increases of maximum flow rate and mean flow rate were
      observed. No adverse reactions were seen. Judging from the above results, this
      treatment is considered to be useful for patients with BPH.

PMID- 7517624
TI  - Loratadine and ventricular tachycardia.

PMID- 7517625
TI  - Nitric oxide in the kidney: synthesis, localization, and function.
AB  - The characterization and cloning of constitutive and inducible nitric oxide (NO)
      synthesizing enzymes and the development of specific inhibitors of the L-arginine
      NO pathway have provided powerful tools to define the role of NO in renal
      physiology and pathophysiology. There is increasing evidence that endothelium
      derived NO is tonically synthesized within the kidney and that NO plays a crucial
      role in the regulation of renal hemodynamics and excretory function. Bradykinin
      and acetylcholine induce renal vasodilation by increasing NO synthesis, which in
      turn leads to enhancement of diuresis and natriuresis. The blockade of basal NO
      synthesis has been shown to result in decreases of renal blood flow and sodium
      excretion. These effects are partly mediated by an interaction between NO and the
      renin angiotensin system. Intrarenal inhibition of NO synthesis leads to
      reduction of sodium excretory responses to changes in renal arterial pressure
      without an effect on renal autoregulation, suggesting that NO exerts a permissive
      or a mediatory role in pressure natriuresis. Nitric oxide released from the
      macula densa may modulate tubuloglomerular feedback response by affecting
      afferent arteriolar constriction. Nitric oxide produced in the proximal tubule
      possibly mediates the effects of angiotensin on tubular reabsorption. In the
      collecting duct, an NO-dependent inhibition of solute transport is suggested. The
      L-arginine NO pathway is also active in the glomerulus. Under pathologic
      conditions such as glomerulonephritis, NO generation is markedly enhanced due to
      the induction of NO synthase, which is mainly derived from infiltrating
      macrophages. An implication of NO in the mechanism of proteinuria, thrombosis
      mesangial proliferation, and leukocyte infiltration is considered. In summary,
      the data presented on NO and renal function have an obvious clinical implication.
      A role for NO in glomerular pathology has been established. Nitric oxide is the
      only vasodilator that closely corresponds to the characteristics of essential
      hypertension. Using chronic NO blockade, models of systemic hypertension will
      provide new insights into mechanisms of the development of high blood pressure.

PMID- 7517626
TI  - Founder mitochondrial haplotypes in Amerindian populations.
AB  - It had been proposed that the colonization of the New World took place by three
      successive migrations from northeastern Asia. The first one gave rise to
      Amerindians (Paleo-Indians), the second and third ones to Nadene and Aleut
      Eskimo, respectively. Variation in mtDNA has been used to infer the demographic
      structure of the Amerindian ancestors. The study of RFLP all along the mtDNA and
      the analysis of nucleotide substitutions in the D-loop region of the
      mitochondrial genome apparently indicate that most or all full-blooded
      Amerindians cluster in one of four different mitochondrial haplotypes that are
      considered to represent the founder maternal lineages of Paleo-Indians. We have
      studied the mtDNA diversity in 109 Amerindians belonging to 3 different tribes,
      and we have reanalyzed the published data on 482 individuals from 18 other
      tribes. Our study confirms the existence of four major Amerindian haplotypes.
      However, we also found evidence supporting the existence of several other
      potential founder haplotypes or haplotype subsets in addition to the four
      ancestral lineages reported. Confirmation of a relatively high number of founder
      haplotypes would indicate that early migration into America was not accompanied
      by a severe genetic bottleneck.

PMID- 7517627
TI  - mtDNA and Native Americans: a Southern perspective.

PMID- 7517628
TI  - Acute retinal pigment epitheliitis and hepatitis C.

PMID- 7517629
TI  - Antidiuretic hormone-responding nonselective cation channel in distal nephron
      epithelium (A6).
AB  - Arginine vasotocin (AVT, 70 mU/ml) added from the basolateral side transiently
      activated a nonselective cation (NSC) channel with a single-channel conductance
      of 28.5 pS and almost identical selectivity for Na+ and K+ in the apical membrane
      of distal nephron cells (A6) cultured on permeable supports for 10-12 days in
      media containing 10% fetal bovine serum without supplemental aldosterone. The
      open probability (Po) of the NSC channel at the apical resting membrane potential
      in cell-attached patches was approximately 0.09 and increased when the apical
      membrane depolarized. The Po of the NSC channel was decreased by a rise in
      cytosolic Ca2+ concentration within a range of 30 nM-1 microM but not affected by
      cytosolic pH within a range of 6-8. The channel was activated by the application
      of negative pressure (10-60 cmH2O) into the patch pipette. Gadolinium (2 microM),
      an inhibitor of stretch-activated channels, decreased the Po by 40%. This
      blocking action of gadolinium was more effective after the channel was activated
      by stretch, i.e., 2 microM gadolinium decreased the Po by 70% when a negative
      pressure (60 cmH2O) was applied into the patch pipette. Amiloride (10 and 100
      microM) showed a blocking action on the channel only when the NSC channel was
      activated by stretch.

PMID- 7517630
TI  - Physiological role of Ca(2+)-activated and voltage-dependent K+ currents in
      rabbit coronary myocytes.
AB  - The properties and function of Ca(2+)-activated K+ (KCa) and voltage-dependent K+
      (IK) currents of rabbit coronary myocytes were studied under whole cell voltage
      clamp conditions (22 degrees C). Inhibition of KCa by tetraethylammonium chloride
      (1-10 mM) or charybdotoxin (50-100 nM) suppressed noisy outward rectifying
      current elicited by 5-s voltage steps or ramp at potentials > 0 mV, reduced the
      hump of the biphasic ramp current-voltage relation, and shifted by less than +5
      mV the potential at which no net steady-state current is recorded (Enet; index of
      resting membrane potential). Inhibition of steady-state inward Ca2+ currents
      [ICa(L)] by nifedipine (1 microM) displaced Enet by -11 mV. Analysis of steady
      state voltage dependence of IK supported the existence of a "window" current
      between -50 and 0 mV. 4-Aminopyridine (2 mM) blocked a noninactivating component
      of IK evoked between -30 and -40 mV, abolished the hump current during ramps, and
      shifted Enet by more than +15 mV; hump current persisted during 2-min ramp
      depolarizations and peaked near the maximum overlap of the steady-state
      activation and inactivation curves of IK (about -22 mV). A threefold rise in
      extracellular Ca2+ concentration (1.8-5.4 mM) enhanced time-dependent outward K+
      current (6.7-fold at +40 mV) and shifted Enet by -30 mV. It is concluded that,
      under steady-state conditions, IK and ICa(L) play a major role in regulating
      resting membrane potential at a physiological level of intracellular Ca2+
      concentration, with a minor contribution from KCa. However, elevation of
      intracellular Ca2+ concentration enhances KCa and hyperpolarizes the myocyte to
      limit Ca2+ entry through ICa(L).

PMID- 7517631
TI  - A Na(+)-sensitive cation channel modulated by angiotensin II in cultured
      intestinal myocytes.
AB  - Single-channel currents were recorded in excised inside-out and cell-attached
      patches of cultured cells from the longitudinal smooth muscle of the guinea pig
      ileum. In the presence of symmetrical high-K+ solutions, we identified a voltage
      dependent 12-pS channel. It was reversibly blocked by addition of either Ba2+ or
      Cs+ at the cellular side of the patch but was insensitive to Ca2+ or ATP. This
      channel had poor selectivity concerning cations (PLi > PK = PNa = PCa, where P is
      permeability) and low permeability to anions. Isosmotic substitution of NaCl for
      KCl in the solution facing the cellular side enhanced the channel activity by
      increasing NPo values where N is number of channels and Po is open probability.
      In the cell-attached configuration, the channel was also activated by addition of
      angiotensin II in the bath solution. We propose that this nonselective cation
      channel might play a role in the control of the membrane potential during the
      contractile response of the guinea pig ileum to agonists by keeping the voltage
      sensitive Ca2+ channels open.

PMID- 7517632
TI  - Anion-induced dynamic behavior of apical water channels in vasopressin-sensitive
      epithelia exposed to mercury.
AB  - We showed recently that, in toad skins preexposed to Hg, water permeability is
      high in SO4-Ringer and low in Cl-Ringer. This anion effect was further
      investigated in Hg-treated skins and bladders of toads (Bufo marinus) in a
      variety of experimental conditions, including glutaraldehyde fixation and
      stimulation by vasopressin (VP) or isoproterenol (IP). In fixed bladders either
      unstimulated or stimulated with VP, net water flow (Jw) in SO4-Ringer [Jw (SO4)]
      was always significantly higher than Jw in Cl [Jw (Cl)]; the same applies to
      fixed toad skins, either unstimulated or stimulated with IP. In unfixed isolated
      toad epidermis challenged with IP before Hg exposure, Jw(SO4)/Jw(Cl) >> 1
      approaching the ratio Jw (maximally stimulated)/Jw (basal). Therefore, anion
      induced Jw changes were present whether Hg acted on epithelial water channels
      exocytosed by Hg itself or by hydrosomotic agents and suggest a switching between
      open and closed configurations of the channel protein. This anion effect was not
      abolished by glutaraldehyde and might be correlated with changes in intracellular
      chloride.

PMID- 7517633
TI  - Radiotracer studies of cystic fibrosis transmembrane conductance regulator
      expressed in Xenopus oocytes.
AB  - We measured fluxes of radiotracers in Xenopus oocytes expressing the cystic
      fibrosis transmembrane conductance regulator (CFTR). Addition of adenosine 3',5'
      cyclic monophosphate (cAMP)-elevating agents [forskolin and 3-isobutyl-1
      methylxanthine (I/F)] led to large increases in uptake of 36Cl, 125I, and 82Br
      into oocytes expressing wild-type CFTR or delta F508 CFTR but not sham-injected
      oocytes. I/F also stimulated halide efflux from CFTR and delta F508 oocytes in
      the sequence Cl > Br > I. cAMP-induced increases in 36Cl efflux from delta F508
      oocytes were approximately 20% of those in CFTR oocytes. Increases in halide
      efflux were blocked by diphenylamine-2-carboxylic acid but not by 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid. The phorbol ester, phorbol 12
      myristate 13-acetate, also stimulated 36Cl efflux from CFTR oocytes. ATP uptakes
      into CFTR and sham oocytes were similar, and both were reduced by I/F. However,
      ATP uptake into I/F-treated CFTR oocytes was slightly greater (approximately 40%)
      than into I/F-treated sham oocytes. Urea uptake into CFTR and sham oocytes was
      similar and in both cases was increased by I/F. However, the I/F-induced increase
      in urea uptake into CFTR oocytes was significantly greater than for sham oocytes.
      I/F stimulated formate uptake into CFTR oocytes but not into sham oocytes. Fluxes
      of 22Na, 86Rb, 35SO4, 32PO4, and mannitol were unaltered by expression and
      activation of CFTR.

PMID- 7517634
TI  - Perforated-patch recording does not enhance effect of 3-isobutyl-1-methylxanthine
      on cardiac calcium current.
AB  - Conventional whole cell voltage-clamp recording results in washout of the cardiac
      Ca2+ current (ICa) response to the beta-adrenergic agonist isoproterenol (Iso),
      for reasons which are not clear. When dose-response curves for the
      phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) were
      compared using perforated-patch vs. conventional whole cell recording in guinea
      pig ventricular myocytes, the conventional whole cell IBMX responses were
      unexpectedly larger than the perforated-patch responses. Furthermore, during
      conventional whole cell recording the response to repeated application of Iso
      declined rapidly, whereas the IBMX response initially increased and then
      declined. When pipette [Ca2+] was increased to 10(-7) M, conventional whole cell
      responses to 300 microM IBMX and 10(-9) M Iso were identical to perforated-patch
      responses. Thus loss of the Iso response during conventional whole cell recording
      seems to not be solely due to a washout of some constituent of the adenosine
      3',5'-cyclic monophosphate pathway. We suggest that unphysiological intracellular
      [Ca2+] enhances the relative PDE activity and that this contributes to the rapid
      decline of the Iso response and the initial enhancement of the IBMX response.

PMID- 7517636
TI  - Heterogeneity of endosomal populations in the rat renal cortex: light endosomes.
AB  - The endosomal pathway of the rat renal cortex was labeled by intravenous infusion
      of fluorescent dextran small enough to cross the glomerular ultrafiltration
      barrier and be taken up by luminal endocytosis in the proximal tubule. Using
      Percoll gradient centrifugation, we isolated and characterized a previously
      undetected renal cortical endosomal fraction slightly lighter than basolateral
      membranes. Assay of entrapped dextran on a vesicle-by-vesicle basis using small
      particle flow cytometry techniques demonstrates homogeneity for entrapped
      dextran. Flow cytometry colocalization of entrapped markers with brush-border
      enzymes in > 99% of the vesicles and the absence of Na-K-adenosinetriphosphatase
      (ATPase) suggest both that these vesicles are of apical origin and that apical
      enzymes traffic into endosomal elements. Furthermore, two glycoproteins derived
      from intermicrovillar clefts are detectable in this fraction. Ultrastructurally
      the vesicles are heterogeneous, consisting of multivesicular bodies together with
      vesicles of diverse size and coating. Populations of vesicles can be cleanly
      separated from each other and basolateral membranes according to their surface
      charge by high-resolution free-flow electrophoresis. Multiparameter flow
      cytometry analysis demonstrates that a more abundant population of smaller
      vesicles has brisker H(+)-ATPase activity, whereas a less abundant population of
      larger vesicles has slower H(+)-ATPase activity. In contrast, brush-border
      membrane vesicles contained no entrapped markers and lacked H(+)-ATPase activity.
      Analysis of vesicles prepared after addition of dextran to the homogenate
      confirms that the vesicles form in vivo. Hence a heterogeneous renal cortical
      endosomal population is of apical origin.

PMID- 7517637
TI  - Somatostatin inhibits CCK release by inhibiting secretion and action of CCK
      releasing peptide.
AB  - We hypothesized that somatostatin exerts its inhibitory action on cholecystokinin
      (CCK) release and pancreatic secretion by inhibiting the secretion and/or action
      of a CCK-releasing peptide (CCK-RP) secreted from the small intestine. Our
      studies demonstrated that intravenous infusion of somatostatin (25 micrograms.kg
      1.h-1) completely inhibited the increase in amylase output evoked by diversion of
      bile-pancreatic juice and 80 +/- 10% of the increase in plasma CCK. Intraduodenal
      administration of concentrated intestinal perfusate containing the CCK-RP
      collected from a donor rat with bile-pancreatic juice diversion raised amylase
      output by 2.3-fold and elevated plasma CCK levels to 7 +/- 0.8 pM in a recipient
      rat. The stimulatory effect of the concentrated intestinal washings was abolished
      when the "donor" rat was pretreated with somatostatin. In addition, in
      somatostatin-treated "recipient" rats, intraduodenal administration of intestinal
      washings containing CCK-RP also failed to elicit an increase in plasma CCK and
      amylase secretion. Furthermore, using duodenal mucosal explants, we demonstrated
      that the inhibitory action of somatostatin on CCK release evoked by CCK-RP was
      antagonized by pretreatment with pertussis toxin. These observations strongly
      suggest that somatostatin inhibits feedback regulation of pancreatic enzyme
      secretion by inhibiting both the secretion and action of CCK-RP.

PMID- 7517635
TI  - K+ modulation of microglial superoxide production: involvement of voltage-gated
      Ca2+ channels.
AB  - A variety of cytoactive factors produced during injury and inflammation are known
      to activate the central nervous system (CNS) macrophage, the microglia. Since
      extracellular potassium levels are known to rise rapidly at sites of injury in
      the CNS, we examined the possibility that changes in extracellular potassium
      could mediate changes in microglial function. The effect of an increase in
      potassium concentration on microglial superoxide anion production was studied in
      cultured neonatal rat microglia. Rather than directly inducing superoxide anion
      production, exposure to media containing 25 and 55 mM potassium enhanced the
      production of superoxide induced by phorbol 12-myristate 13-acetate. This
      potentiation was blocked by nifedipine, a voltage-gated calcium channel blocker.
      Treatment of the microglia with BAY K 8644, an agonist for voltage-gated calcium
      channels, produced an enhancement of superoxide levels similar to that of
      potassium. Because these data indicated the presence of a voltage-gated calcium
      channel, we also examined whole cell current in cultured microglia. A small,
      voltage-dependent inward calcium current was seen that was increased by exposure
      of the microglia to BAY K 8644. The presence of a small but finite calcium influx
      via these channels may be an important factor in the regulation of intracellular
      microglial events such as activation of the NADPH oxidase and the consequent
      production of superoxide anion.

PMID- 7517638
TI  - Microvascular permeability in isolated vascularly perfused small intestine of
      rats.
AB  - Intestinal microvascular permeability was studied in the isolated vascularly
      perfused small intestine of the rat by arterial injection of tracer molecules and
      collection of venous samples. The injection mixture contained a rhodamine-labeled
      dextran and a fluorescein-labeled dextran or free fluorescein. Pharmacokinetic
      analysis, based on statistical moment theory, of the tracer outflow concentration
      time curve and the application of either the well-stirred model (WSM) or parallel
      tube model (PTM) was used to assess vasopermeability. The results indicate that
      the experimental system cannot be considered a pure WSM or a PTM. No different
      intrinsic clearance (Clint,i) values were found by applying the two models:
      Clint,i (in ml/min) = 1.23 +/- 0.14 (radius 0.5 nm); 0.44 +/- 0.09 (radius 1.4
      nm); 0.31 +/- 0.08 (radius 2.2 nm); 0.02 +/- 0.01 (radius 6.0 nm); and 0 (radius
      20.8 nm). Infusion of histamine (10(-5)-10(-3) M) and destruction of the
      endothelium via perfusion with distilled water increased the permeability for the
      tracers. We have established a technique for measurement of microvascular
      permeability characteristics in the rat small intestine. Histamine-induced
      changes and destruction of the endothelium can be detected in a quantitatively
      reliable way.

PMID- 7517639
TI  - Pancreatic tumoral cell line AR42J: an amphicrine model.
AB  - AR42J cells derive from azaserine-induced malignant nodules from the rat
      pancreas. They differ from normal acinar cells for at least three reasons: 1)
      they proliferate rapidly; 2) they synthesize, store, and secrete digestive
      enzymes but the regulation of their exocrine function is abnormal, from the
      emergence of atypical receptors (e.g., cholecystokinin octapeptide type B and
      pituitary adenylate cyclase-activating polypeptide type I receptors) to unusual
      inositol phosphate metabolism and cytoskeleton disorganization; and 3) they
      possess an added neuroendocrine-regulated pathway characterized by voltage
      sensitive ionic currents, post-translational processing of peptidic prohormones
      (and possibly autocriny), and the release of small neurotransmitters (gamma
      aminobutyric acid, glycine, and glutamic acid). These amphicrine cells represent,
      therefore, a cancerous version of the primordial pancreatic ductular epithelium.
      Dexamethasone favors their differentiation toward the exocrine phenotype. The
      mitogenic pathway is favored by the occupancy of receptor tyrosine kinases,
      adenosine 3',5'-cyclic monophosphate, ornithine decarboxylase expression, and
      Na(+)-H+ exchange. Somatostatin opposes proliferation through protein
      phosphatases.

PMID- 7517640
TI  - Nitric oxide synthase type I and type III gene expression are developmentally
      regulated in rat lung.
AB  - The successful transition from fetal to neonatal life involves a marked decline
      in pulmonary vascular resistance which is modulated in part by endothelium
      derived nitric oxide. To define the molecular processes which prepare the
      pulmonary circulation for nitric oxide mediation of vasodilatation at the time of
      birth, we determined the ontogeny of endothelial nitric oxide synthase (NOS-III)
      gene expression in lungs from fetal and newborn rats. Maturational changes in
      lung neuronal NOS (NOS-I) expression were also investigated; the latter isoform
      has been localized to rat bronchiolar epithelium. NOS proteins were examined by
      immunoblot analysis, and mRNA abundance was assessed in reverse transcription
      polymerase chain reaction assays. Both NOS-III and NOS-I protein were detectable
      in 16-day fetal lung, they increased 3.8- and 3.1-fold, respectively, to maximal
      levels at 20 days of gestation (term = 22 day), and they fell postnatally (1-5
      days). In parallel with the findings for NOS-III protein, NOS-III mRNA increased
      from 16 to 20 days gestation and fell after birth. In contrast, NOS-I mRNA
      abundance declined during late fetal life and rose postnatally. These findings
      were confirmed by Northern analyses. Thus NOS-III and NOS-I gene expression are
      developmentally regulated in rat lung, with maximal NOS-III and NOS-I protein
      present near term. The regulation of pulmonary NOS-III may primarily involve
      alterations in transcription or mRNA stability, whereas NOS-I expression in the
      maturing lung may also be mediated by additional posttranscriptional processes.

PMID- 7517641
TI  - Immunochemical detection of inducible NO synthase in human lung.
AB  - Type II (inducible) nitric oxide synthase (NOS) may play an important role in
      pulmonary pathophysiology, yet it remains controversial whether human tissues are
      capable of expressing this protein. Therefore, a polyclonal antibody (8196) was
      raised against type II NOS from induced RAW 264.7 macrophages and used to
      investigate the expression of this enzyme in human lung tissue. Anti-type II NOS
      antibody did not cross-react with either neuronal (type I) or endothelial (type
      III) constitutive NOS, whereas a 130-kDa protein was detected in cytosol from
      induced macrophages or liver removed from lipopolysaccharide (25 mg/kg)-treated
      rats. Cells or tissues that lacked NOS activity did not express immunoreactive
      proteins. Similarly, in grossly normal human lung tissue, no immunoreactivity was
      detected with the anti-type II NOS antibody. In contrast, strong immunoreactivity
      was detected in alveolar macrophages present in lung tissue from a patient with
      bronchiectasis and acute bronchopneumonia. These data demonstrate that human
      alveolar macrophages are able to express type II NOS and support a role for this
      enzyme in pulmonary inflammatory pathophysiology.

PMID- 7517642
TI  - H(+)-ATPases of renal cortical and medullary endosomes are differentially
      sensitive to Sch-28080 and omeprazole.
AB  - Adenosinetriphosphatase (ATPase) activity stimulated by K+ and inhibited by Sch
      28080 (SCH), omeprazole (OME), and vanadate has been measured in microsomes from
      mammalian renal medulla and attributed to a kidney isoform of the H(+)-K(+)
      ATPase. To determine whether the H(+)-K(+)-ATPase inhibitors could also inhibit
      the vacuolar (V)-type H(+)-adenosinetriphosphatase (H(+)-ATPase, i.e., H+ pump)
      in mammalian intracellular vesicles, we examined their effects on bafilomycin
      sensitive acidification in renal cortical vesicles (CEV) and medullary endocytic
      vesicles (MEV). Rats were injected with fluorescein isothiocyanate-labeled
      dextran, and labeled endosomes were enriched from kidney tissue homogenates by
      differential and Percoll density gradient centrifugation. In the CEV, the V-type
      H+ pump was inhibited 25% by SCH and 30% by OME (100 microM each). Whereas the
      inhibition by OME was concentration and time dependent, the inhibition by SCH was
      only concentration dependent. Inhibition by these compounds was similar in the
      presence of 50 mM K+ (in = out) and in the complete absence of K+, thus ruling
      out a significant involvement of H(+)-K(+)-ATPase-mediated acidification.
      Inhibition, however, was not observed with 10 microM SCH and OME. The sensitivity
      of the V-type H+ pump to 100 microM SCH and OME in CEV was confirmed by the
      comparable inhibitions of intravesicular acidification observed in acridine
      orange fluorescence quench studies and by inhibition of Pi liberation in an
      ATPase assay. We also found that the V-type H+ pump in isolated rat liver
      endosomes is sensitive to 100 microM SCH and OME to a similar degree. In the MEV,
      acidification was only weakly affected by 100 microM SCH and OME, thus suggesting
      that H(+)-ATPases in endosomes from cortical and medullary tubules are different,
      possibly due to a previously described selective expression of subunit isoforms.
      Our finding indicates the importance of using low concentrations (< 10 microM) of
      OME and SCH in studies of H(+)-K(+)-ATPase in nongastric tissues to avoid
      misinterpretation of the data due to nonspecific inhibition of V-type H(+)
      ATPases.

PMID- 7517643
TI  - Inhibition of bicarbonate transport in peanut lectin-positive intercalated cells
      by a monoclonal antibody.
AB  - Intercalated cells (ICC) of the collecting duct are believed to secrete acid
      (alpha-type) or HCO3 (beta-type). Although these two types of ICC are
      functionally mirror images of each other, several components in their cell
      membranes are clearly unique. As a first step in defining the molecular
      composition of beta-ICC membranes, we raised cell-specific monoclonal antibodies
      (MAb) against surface antigens. One of these MAb, designated B63, reacts with the
      apical membrane of peanut lectin agglutinin (PNA)-positive cells of the kidney
      cortex. B63-positive cells do not react with antibodies against band 3 (the
      basolateral C1/HCO3 exchanger) or ST.48, markers for alpha-ICC and principal
      cells, respectively. Despite a significant positive correlation between PNA and
      B63 staining intensities, determined by flow cytometry, these markers react with
      separate antigens, as indicated by competition studies and the different
      distribution of the two antigens. In addition to renal beta-ICC, B63 antigen is
      present in tissues that are involved in HCO3 secretion, such as the pancreas,
      salivary glands, and the small intestine, suggesting that it might play a role in
      HCO3 secretion. To test this hypothesis more directly, we tested the effect of
      MAb B63 on HCO3 secretion and on changes in intracellular pH (pHi) in isolated
      perfused cortical collecting ducts. Luminal Cl removal in the presence of luminal
      4,4'-diisothiocyanostilbene-2,2'-disulfonic acid resulted in a reversible
      increase in pHi. Luminal application of MAb B63 prevented this change in pHi. MAb
      B63 also significantly inhibited (by 37.7 +/- 7.3%) HCO3 secretion by isolated
      perfused tubules, whereas another MAb (MAb 601), which reacts with a separate
      antigen on beta-ICC, did not alter HCO3 secretion or pHi. These results indicate
      that B63 antigen plays an important role in HCO3 secretion: it might be either
      the apical anion exchanger of beta-ICC or an associated regulatory protein.

PMID- 7517644
TI  - Macrophages, monocyte chemoattractant peptide-1, and TGF-beta 1 in experimental
      hydronephrosis.
AB  - Early cellular and molecular derangements have been evaluated as potential
      pivotal factors for the late development of interstitial fibrosis after
      experimental hydronephrosis. In this study, we delineated the kinetics of renal
      cortical macrophage infiltration as well as the cortical expression of
      transforming growth factor-beta 1 (TGF-beta 1) and monocyte chemoattractant
      peptide-1 (MCP-1) at 12, 48, and 96 h after unilateral ureteral obstruction
      (UUO). Interstitial macrophage number in the obstructed kidney versus the
      contralateral unobstructed kidney (CUK) significantly increased by 12 (11.1 +/-
      0.9 vs. 4.5 +/- 0.6), 48 (27.5 +/- 0.9 vs. 4.0 +/- 0.8), and 96 h (71.4 +/- 4.6
      vs. 3.2 +/- 0.4) after UUO. MCP-1 mRNA was detected from 12 to 96 h in the
      obstructed kidney but was absent in the CUK specimens at all time points. Apical
      tubular MCP-1 expression, on immunolabeling, was present from 12 through 96 h
      after UUO in the obstructed kidney but not the CUK specimen. On Northern
      analysis, there were highly significant 2.6-, 5.8-, and 7.0-fold increments in
      renal cortical TGF-beta 1 mRNA levels at 12, 48, and 96 h, respectively, in the
      obstructed kidney versus the CUK specimen. Intracellular TGF-beta 1, on
      immunolabeling, was detected only in the obstructed kidneys of UUO rats at all
      three time points and was confined to peritubular cells of the renal
      interstitium. A significant (P < 0.005) correlation (r = 0.95) between
      interstitial macrophage number and cortical TGF-beta 1 mRNA levels was
      noted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517645
TI  - Determination of capillary tube hematocrit during arteriolar microperfusion.
AB  - Intracapillary hematocrit is known to be substantially lower than arterial
      hematocrit. We hypothesized that capillary hematocrit might be influenced by
      interactions between plasma macromolecules and the endothelial cell surface.
      Microvessel perfusion pipettes were inserted in second- or third-order vessels,
      and capillaries were perfused with three different artificial bloods composed of
      50% red cells plus the following suspension media: fetal calf serum (group I),
      serum albumin plus serum globulins (fractions II and III; group II), and bovine
      serum albumin plus dextran (group III). The mean hematocrits of the pipette
      perfused capillaries averaged close to 50% of the systemic value with all
      perfusion fluids and were not different from the hematocrits of the capillaries
      perfused by the animal. These data suggest that bifurcations proximal to the
      pipette location did not contribute to the reduction in mean tube hematocrit
      normally seen in the animal. Furthermore, interactions between the plasma
      macromolecules and the endothelial cell surface do not appear to contribute to
      the low intracapillary hematocrit. Analysis of the data indicate that the
      capillary Fahraeus effect, the network Fahraeus effect in terminal vessels of the
      arterial tree, and intracapillary events all contribute to the reduction in
      intracapillary hematocrit.

PMID- 7517647
TI  - Comparative effects of L-NNA and alkyl esters of L-NNA on pulmonary vasodilator
      responses to ACh, BK, and SP.
AB  - The comparative effects of the nitric oxide (NO) synthase inhibitors N omega
      nitro-L-arginine (L-NNA), N omega-nitro-L-arginine methyl ester (L-NAME), and N
      omega-nitro-L-arginine benzyl ester (L-NABE) on baseline tone and on vasodilator
      responses to acetylcholine (ACh), bradykinin (BK), and substance P (SP) were
      compared in the pulmonary vascular bed of the cat under constant flow conditions.
      After administration of the NO synthase inhibitors in intravenous doses of 100
      mg/kg, the increase in lobar arterial pressure and the attenuation of vasodilator
      responses to ACh, BK, and SP were similar, whereas responses to adenosine and
      felodipine, endothelium-independent vasodilator agents, were not altered. In
      addition to inhibiting responses to ACh, BK, and substance P, the NO synthase
      inhibitors enhanced vasodilator responses to S-nitroso-N-acetylpenicillamine and
      NO. Moreover, atropine inhibited pulmonary vasodilator responses to ACh but not
      to SP or BK, and L-NAME or L-NABE had no effect on the decrease in heart rate in
      response to efferent vagal stimulation, a muscarinic receptor-mediated response
      that is independent of NO release. The similar inhibitory effects of L-NNA, L
      NAME, and L-NABE on vasodilator responses to ACh, BK, and SP suggest that the L
      arginine analogue, L-NNA, as well as the methyl and benzyl esters of L-NNA are
      useful probes for studying NO-mediated endothelium-dependent responses in the
      pulmonary vascular bed of the intact-chest cat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517646
TI  - Analysis of responses to bradykinin in the pulmonary vascular bed of the cat.
AB  - Responses to bradykinin (BK) were investigated in the pulmonary vascular bed of
      the cat under conditions of controlled pulmonary blood flow and constant left
      atrial pressure when lobar arterial pressure was elevated to a high steady level.
      Under elevated-tone conditions, BK caused dose-related decreases in lobar
      arterial pressure. After administration of Hoe-140, a BK B2-receptor antagonist,
      vasodilator responses to BK were reduced in a selective manner. Vasodilator
      responses to BK were unchanged by atropine, glibenclamide, meclofenamate, or
      bronchial occlusion, suggesting that responses are not dependent on the
      activation of muscarinic receptors or K+ATP channels, the release of vasodilator
      prostaglandins, or changes in bronchomotor tone. The nitric oxide (NO) synthase
      inhibitors N omega-nitro-L-arginine benzyl ester and N omega-nitro-L-arginine
      reduced vasodilator responses to BK in a selective manner, indicating that
      responses to BK are mediated in part by the release of NO. Methylene blue, an
      inhibitor of the activation of soluble guanylate cyclase, increased lobar
      arterial pressure and decreased responses to BK. The increases in lobar arterial
      pressure in response to methylene blue were partially reversed by the
      administration of superoxide dismutase, indicating that generation of O2- may
      inactivate basally released NO. The duration of the response to BK was enhanced
      by the guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor
      Zaprinast, suggesting that responses to BK involve increases in cGMP levels.
      Responses to BK were enhanced by captopril, indicating that BK is rapidly
      inactivated by kininase II in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517648
TI  - The clinical challenge of multiple pancreatic pseudocysts.
AB  - To evaluate the frequency of multiple pancreatic cysts, the likelihood of
      preoperative diagnosis, and therapeutic outcome, we retrospectively reviewed the
      records of 157 patients who underwent operation for pancreatic pseudocysts at 2
      institutions between 1970 and 1992. Multiple pseudocysts were found in 29
      (18.5%). The 8 women and 21 men ranged in age from 21 to 79 years. The etiology
      was alcohol abuse in 15 (52%), biliary tract disease in 6 (21%), alcohol abuse
      and biliary tract disease in 3 (10%), and a variety of other causes in the
      remaining 5 (17%). There was no difference in age, sex, race, etiology, or
      presenting signs and symptoms between patients with single pseudocysts and those
      with multiple cysts. Serum amylase levels were significantly higher in patients
      with multiple cysts compared to those with single cysts (P < 0.05). Computed
      tomography accurately demonstrated the extent of disease in 20 of 25 patients
      (80%), while 1 or more cysts were missed in 5 (20%). The mean number of cysts per
      patient was 2.7, with a range of 2 to 5. Average pseudocyst diameter was 7.8 cm,
      with a range from 3 to 20 cm. Multiple internal drainage procedures were
      performed in 19 patients, a combination of internal and external drainage in 6,
      external drainage in 1, and resection of multiple cysts in the tail in 2. There
      was no operative mortality. With a mean follow up of 38.5 months, only 1
      recurrent pseudocyst has been found. There were six attempts at percutaneous
      drainage in six patients. Two of these patients were referred to our institution
      following failure of percutaneous drainage at other hospitals. Three other
      patients had residual symptomatic pseudocysts following percutaneous drainage at
      our hospitals and then underwent multiple internal drainage. The sixth patient
      refused operative drainage despite the persistence of residual symptomatic
      pseudocysts after attempted percutaneous drainage. The incidence of multiple
      pseudocysts (18.5%) is higher than previously reported. There is no difference in
      the clinical features of patients with single versus multiple pseudocysts.
      Patients with multiple cysts have higher serum amylase levels. Preoperative
      computed tomography underestimated the number of cysts in 20% of patients.
      Careful intraoperative exploration is still needed to avoid missing multiple
      pseudocysts. Internal drainage is the preferred therapy. A thorough search for
      multiple cysts at the initial operation should eliminate one potential cause for
      pseudocyst recurrence.

PMID- 7517651
TI  - Gene transfer into hematopoietic cells. Implications for cancer therapy.

PMID- 7517650
TI  - Cause of hypotension after isolated limb perfusion with tumor necrosis factor.

PMID- 7517652
TI  - Gene therapy and endothelial cell targeting for cancer.
AB  - The endothelium represents a potentially critical target for gene therapy because
      of its anatomical location and its importance in the viability in both normal and
      malignant tissues. Protecting the endothelium of normal tissues, such as the
      lungs, from the toxic effects of current antineoplastic agents and the
      destruction of the tumor vasculature are reasonable goals. As a target, however,
      the endothelium continues to represent a significant challenge. While gene
      delivery to cultured endothelial cells is possible, improved delivery systems are
      required, as well as cell-specific promoters, before in vivo gene therapy to
      important endothelial populations can be accomplished.

PMID- 7517653
TI  - Adenovirus-mediated in vivo gene transfer.
AB  - Adenovirus vectors are efficient vehicles for in vivo gene transfer to many
      different cell types. Recombinant adenovirus vectors containing exogenous genes
      for transfer are derived from adenovirus type 5 and are made replication
      deficient by the deletion of the E1 region. Based on the observation that many
      natural adenovirus infections are targeted to airway epithelial cells, a
      replication-deficient adenovirus vector was constructed containing the cystic
      fibrosis transmembrane conductance regulator cDNA for the potential therapy of
      the respiratory manifestations of cystic fibrosis. Using this vector, the normal
      human CFTR cDNA has been successfully transferred to airway epithelial cells of
      experimental animals via the trachea. This finding has led to the development of
      human gene therapy protocols for the evaluation of the safety and efficacy of
      adenovirus-mediated CFTR cDNA transfer to lungs of individuals with cystic
      fibrosis. In addition to the airways, adenovirus vectors have been demonstrated
      to mediate in vivo gene delivery to cells of the liver, blood vessels, brain,
      muscle, heart, peritoneum, and salivary glands. Adenovirus vectors containing
      marker genes have also been demonstrated to transfer genes to human tumor cells
      in nude mice. Such vectors may be useful for a variety of therapeutic
      applications for in vivo gene transfer for the therapy of cancer and other
      diseases.

PMID- 7517649
TI  - Living related liver transplantation in children.
AB  - We reviewed 37 living related liver transplantations (LRLT) performed by our
      department during the last 27 months on children with end-stage liver disease.
      The patients were 15 boys and 22 girls aged 7 months to 15 years with biliary
      atresia (27), cryptogenic cirrhosis (3), Budd-Chiari syndrome (2), progressive
      intrahepatic cholestasis (2), protoporphyria (1), Wilson's disease (1), and
      fulminant hepatitis (1). The donors were 14 fathers and 23 mothers. Grafts were
      made from the left lateral segment (19), left lateral segment with partial S4
      (11), left lobe (6), and right lobe (1). After graft harvesting all donors
      resumed normal liver function and normal life. The recipient underwent total
      hepatectomy with preservation of the inferior vena cava. FK506 and low-dose
      steroids were used for immunosuppression. The survival rate was 90% (27/30) in
      elective cases and 57% (4/7) in emergency cases. Six recipients had functioning
      grafts but died of extrahepatic complications. Hepatic vein stenosis occurred in
      3 cases at 3 months after LRLT and was successfully treated by balloon
      dilatation. Portal vein stenosis occurred in 1 case at 8 months after LRLT and
      was also safely dilated. We incurred no hepatic artery thrombosis after
      introducing microsurgery techniques. Among 12 viral, 5 bacterial, and 3 fungal
      postoperative infections, 1 Candida pneumonia and 1 EBV-associated lymphoma were
      lethal. Three patients with ABO-blood group compatible grafts and one with an
      incompatible graft developed acute rejection, which was controlled in evey case
      by steroid bolus and/or increasing the dose of FK506. There were no definite
      episodes of rejection in ABO-identical cases. Children with moderate growth
      retardation (> or = -1.5 SD of normal growth) caught up in growth soon after
      LRLT, but those with severe retardation (<-1.5 SD) were slow to attain age-normal
      height. Appropriate timing, meticulous surgical procedures, and comprehensive
      management of complications are crucial for successful outcome with LRLT. LRLT is
      a promising option for alleviating the shortage of livers for pediatric
      transplantation and may be regarded as an independent modality to supplement
      cadaver donation.

PMID- 7517655
TI  - Immunohistochemistry of port-wine stains and normal skin with endothelium
      specific antibodies PAL-E, anti-ICAM-1, anti-ELAM-1, and anti-factor VIIIrAg.
AB  - BACKGROUND AND DESIGN: Immunohistochemical analysis using four monoclonal
      antibodies specific for endothelium was performed to evaluate the possible role
      the endothelium may play in the pathogenesis of port-wine stains. In 11 patients
      with port-wine stains, biopsy specimens were obtained from involved and normal
      skin. On frozen tissue sections, we studied and compared the distribution and
      staining pattern of PAL-E, anti-intercellular adhesion molecule-1 (ICAM-1), anti
      endothelial leukocyte adhesion molecule-1 (ELAM-1), and anti-factor VIIIrAg
      (FVIIIrAg), all recognizing specific epitopes of vascular endothelial cells.
      RESULTS: The PAL-E, anti-FVIIIrAg, and anti-ICAM-1 antibodies showed a similar
      distribution and staining pattern. The intensity of staining was equally strong
      with PAL-E and FVIIIrAg, while the expression of ICAM-1 was moderate. The ELAM-1
      antibody exhibited only a weak expression in about 70% of evaluated specimens. No
      substantial differences in the intensity and distribution pattern of expression
      of these proteins could be demonstrated between normal skin and port-wine stains.
      CONCLUSION: Our findings suggest that the abnormal vessel pathologic findings in
      port-wine stains are not due to defects associated with the endothelium.
      According to PAL-E antibody staining properties, port-wine stain vessels could be
      classified as capillaries and/or postcapillary venules and small veins.

PMID- 7517654
TI  - Parkinson's disease and brain levels of organochlorine pesticides.
AB  - Epidemiological studies have suggested an etiologic relationship between
      pesticide exposure and Parkinson's disease (PD). Organochlorine pesticides were
      assayed in postmortem brain samples from 20 PD, 7 Alzheimer's disease (AD), and
      14 nonneurological control cases. The three groups were similar in age at death,
      sex, and demographic variables. Only two of 16 pesticide residues screened were
      detected. A long-lasting residue of DDT (pp-DDE) was found in the majority of
      cases of PD and AD, as well as in all the control cases; pp-DDT was significantly
      more likely to be found in AD controls than the PD cases (Fisher's exact two
      tailed, p = 0.04). Dieldrin was detected in 6 of 20 PD brains, 1 of 7 AD, and in
      none of 14 control samples. Despite the relatively small number of brains
      assayed, the association between Dieldrin and the diagnosis of PD was highly
      significant (p = 0.03). Dieldrin, a lipid-soluble, long-lasting mitochondrial
      poison, should be investigated as a potential etiological agent of Parkinsonism.

PMID- 7517656
TI  - [The advantages of palliative embolization and with preoperative ethanol in
      hypernephroma].
AB  - We report thirty-one embolizations of renal cell carcinomas, using ethanol
      injected through a balloon-tipped catheter. This technique is performed both as a
      palliative and as a preoperative treatment. Renal function (urea and creatinine)
      before and a week after embolization showed no important variations. The CT scan
      six days after embolization disclosed intratumoral gas formation due to necrosis,
      without infection. Less time and fewer transfusions were required with this
      procedure and the morbidity and mortality rates were lower. There were no major
      complications and the duration of the postembolization syndrome was reduced to 48
      hours. A histopathological examination of the tumor and the vascular changes was
      done, showing the effects of ethanol on the arterial and venous walls.

PMID- 7517658
TI  - Human chorionic gonadotropin beta-subunit synthesis by undifferentiated
      urothelial carcinoma with syncytiotrophoblastic differentiation.
AB  - An undifferentiated deeply invasive ureteral carcinoma with syncytiotrophoblastic
      differentiation was analyzed for the synthesis of human chorionic gonadotropin
      beta-subunit by immunohistochemistry and Northern blot analysis. Human chorionic
      gonadotropin beta-subunit was localized immunohistochemically to
      syncytiotrophoblastic cells and scattered mononuclear tumor cells. Human
      chorionic gonadotropin beta-subunit gene was expressed at a high level by
      Northern blot analysis. To our knowledge, this is the first report demonstrating
      the synthesis of human chorionic gonadotropin beta-subunit at the transcriptional
      level in a urothelial carcinoma.

PMID- 7517659
TI  - The significance of lymphoid follicles in the interpretation of gastric biopsy
      specimens.
AB  - Lymphoid follicles are a common feature of Helicobacter pylori-associated
      gastritis. Recently, by using gastric mapping, we demonstrated lymphoid follicles
      in all of 62 patients with H pylori infection. This study was designed to address
      (1) the prevalence of lymphoid follicles in routine gastric biopsy specimens, (2)
      their correlation with chronic active gastritis, and (3) their predictive value
      with respect to H pylori infection. Slides from 174 patients whose gastric biopsy
      findings carried a nonneoplastic diagnosis were evaluated for the presence of (1)
      chronic active gastritis, (2) lymphoid follicles, and (3) H pylori. When either
      follicles or active gastritis was found, but H pylori could not be identified by
      the hematoxylin-eosin stain, additional slides were prepared with a newly
      developed silver-hematoxylin-eosin-alcian blue stain. Active gastritis was
      present in 153 patients (88%). Helicobacter pylori was identified on hematoxylin
      eosin-stained slides in 123 patients and by the modified Steiner stain in 11
      additional patients. Thus, 87% of the patients with chronic active gastritis had
      histologically detectable H pylori infection. One or more lymphoid aggregates
      were present in 110 patients (82% of patients with H pylori and 72% of those with
      chronic active gastritis). Of these, 101 (92%) had H pylori infection. In six of
      the nine H pylori-negative patients with lymphoid aggregates, biopsy specimens
      were taken from the edges of an ulcer. In summary, except when biopsy specimens
      are obtained from the immediate vicinity of a gastric ulcer, lymphoid aggregates
      in a gastric biopsy specimen are virtually always associated with chronic active
      gastritis and provide a useful marker for H pylori infection.

PMID- 7517657
TI  - Useful predictors of bile duct stones in patients undergoing laparoscopic
      cholecystectomy. McGill Gallstone Treatment Group.
AB  - OBJECTIVE: The authors determined the most useful predictors of common bile duct
      (CBD) stones as diagnosed by endoscopic retrograde cholangiopancreatography
      (ERCP) in patients who underwent laparoscopic cholecystectomy (LC). METHODS:
      Prospective and retrospective collection of historical, biochemical and
      ultrasonographic data was used. Receiver operating characteristics curve analysis
      was used to determine optimal biochemical cut-off values. Multivariate analysis
      using logistic regression with generation of the best model identifying
      independent predictors of CBD stones also was employed. Prospective validation of
      the model was performed on an independent group of patients. RESULTS: Endoscopic
      retrograde cholangiopancreatographies were performed before LC in 106 patients,
      and after LC in 33. Only four of ten clinical variables evaluated independently
      predicted the presence of CBD stones. The optimal model predicted a 94%
      probability of CBD stones in a patient older than 55 years of age who presented
      with an elevated bilirubin (over 30 mumol/L) and positive ultrasound findings (a
      dilated CBD, and a CBD stone seen on ultrasound). This model was validated
      prospectively in a subsequent series of 49 patients in which the probability of
      CBD stone was only 8% when all four predictors were absent. CONCLUSIONS: The
      identified independent clinical predictors of a CBD stone helps select a
      population of symptomatic gallstone bearers who benefit most from
      cholangiographic assessment.

PMID- 7517662
TI  - Postoperative recurrence of hepatocellular carcinoma. Two hundred five
      consecutive patients who underwent hepatic resection in 15 years.
AB  - OBJECTIVES: To report the results of our investigation of the postoperative
      intrahepatic recurrent rates and the patterns of recurrence and to determine the
      factors that influenced these patterns of recurrence. DESIGN: Case series.
      SETTING: Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan.
      PATIENTS: Between 1977 and 1991, 162 men and 43 women with hepatocellular
      carcinoma underwent hepatic resection. RESULTS: The surgical mortality rate was
      4.4%. Of the 196 patients who were discharged from the hospital, 114 have since
      died and 20 were not available for follow-up. The overall cumulative recurrent
      rates for the last 5 years (1987 through 1991) were 59.7%, 65.0%, 76.5%, 77.0%,
      and 79.7%, respectively. Eighty patients experienced intrahepatic recurrence. Of
      these, 21 (26.2%) had recurrence near the resected stump, 43 (53.8%) had a single
      nodular recurrence in the remnant liver, and 16 (20%) had wide-spread
      multinodular recurrence. The patients with resected margins of less than 1 cm in
      diameter had relatively higher recurrence rates than those with resected margins
      of greater than 1 cm in diameter. All recurrences were noted within 3 years of
      the resection. The preoperative serum alpha-fetoprotein levels were directly
      related to the length of time to recurrence (ie, the higher the serum alpha
      fetoprotein level, the sooner the recurrence). CONCLUSIONS: The postoperative
      intrahepatic remnant rate is very high; 80% by 5 years after resection. The
      preoperative serum alpha-fetoprotein level and adequacy of the cut margin
      significantly influenced the recurrence rate.

PMID- 7517660
TI  - Rhodococcus equi pneumonia and pulmonary malakoplakia in acquired
      immunodeficiency syndrome. Pathologic features.
AB  - Pulmonary infection with Rhodococcus equi is rare, and most cases are seen in
      immunocompromised patients, particularly those with acquired immunodeficiency
      syndrome. We describe the pathologic features in four cases of culture-positive R
      equi pneumonia occurring in patients infected with human immunodeficiency virus.
      All four patients had a solitary cavitary pulmonary mass that was resected (n =
      3) or had undergone biopsy (n = 1). Pathologically, all specimens revealed sheets
      of histiocytes with abundant foamy to eosinophilic cytoplasm with numerous
      phagolysosomes that were positive for periodic acid-Schiff, Gomori methenamine
      silver, and Grocott stains. Occasional histiocytes contained Michaelis-Gutmann
      bodies, diagnostic of malakoplakia. The Michaelis-Gutmann bodies yielded positive
      results with periodic acid-Schiff, Gomori methenamine silver, Grocott, Giemsa,
      and von Kossa stains (three of three cases studied) and with alizarin red and
      Prussian blue stains (two of three cases studied). Many gram-positive
      coccobacilli within histiocytes and associated with neutrophils were found in one
      case. Ultrastructural study of one case showed histiocytes containing abundant
      phagolysosomes with degenerated bacterial components and Michaelis-Gutmann
      bodies. The latter had a targetoid appearance with variegated phagolysosome cores
      that were mineralized by deposition of electron-dense spicules surrounded by
      peripheral rings of granular and membranous material. Based on our observations
      and reports in the literature, there appears to be a more than coincidental
      association between pulmonary R equi infection, malakoplakia, and human
      immunodeficiency virus infection.

PMID- 7517661
TI  - The malignant transformation of liver cell adenomas.
AB  - OBJECTIVE: To investigate clinical experience with the apparent malignant
      transformation of benign liver cell adenomas. DESIGN: Retrospective review of
      personal experience and literature. SETTING: University hospital and affilated
      community hospitals. PATIENTS: All patients diagnosed with liver cell adenomas
      over a 30-year period. INTERVENTIONS: Liver resection and/or tumor biopsy. MAIN
      OUTCOME MEASURES: Gender, age, drug associations, alpha-fetoprotein levels,
      response to treatment, and survival. RESULTS: Thirteen patients from personal
      experience and 26 patients from the reports of others had liver cell adenomas
      that were not resected. Five of these patients subsequently developed
      hepatocellular carcinoma. CONCLUSIONS: Malignant transformation of a liver cell
      adenoma is a rare phenomenon, but it does occur. Alpha-fetoprotein levels may be
      more helpful in diagnosis than expected from previous reports. Solitary benign
      adenomas should be resected whenever possible. Patients with diffuse multiple
      tumors should be observed closely over a long period.

PMID- 7517663
TI  - Effect of a long-term change from a mixed to a lactovegetarian diet on human
      saliva.
AB  - The effects of this long-term dietary change on secretion rate, buffer capacity,
      concentration of sodium and potassium and amylase activity of stimulated parotid
      and whole saliva was studied in 20 healthy, normal-weight, non-smoking omnivores.
      Salivary counts of mutans streptococci and lactobacilli were also made. Dietary
      surveys were carried out and saliva samples collected before (baseline) and 3, 6
      and 12 months after the dietary change as well as 3 yr after the end of the
      lactovegetarian diet period. The dietary data showed an increase in the
      consumption of fruits, vegetables and dairy products and a decrease in meat,
      fish, eggs, sweets and biscuits. These changes led to an increased intake of
      carbohydrates, fibre and water. After 12 months on the vegetarian diet, the
      secretion rate, buffer capacity and sodium concentration of whole saliva and the
      secretion rate of parotid saliva had increased significantly. At the 3-yr follow
      up, the buffer capacity and sodium concentration were still elevated, while the
      secretion rate had almost returned to the baseline values. The potassium content
      of whole saliva showed a tendency to increase during the vegetarian diet period,
      but had decreased again at the 3-yr follow-up.

PMID- 7517664
TI  - Binding and bioeffects of Ipriflavone on a human preosteoclastic cell line.
AB  - Ipriflavone, a synthetic isoflavone derivative, reduces bone resorption by
      inhibiting osteoclasts activity. In order to evaluate the role of Ipriflavone on
      osteoclast growth and differentiation, we tested Ipriflavone and its four "in
      vivo" main metabolites (Metabolites I, II, III, and V) on a clonal population of
      human osteoclast precursor cells (FLG 29.1). Pharmacological doses of Ipriflavone
      and Metabolite III were able to inhibit cell proliferation and interleukin 6
      release. In co-cultures of FLG 29.1 cells and osteoblastic (Saos-2) cells
      Ipriflavone at 1 microM dose inhibited the adhesion of FLG 29.1 cells to the
      osteoblastic monolayer and reduced the immunocytochemical reaction of the
      vitronectin receptor. Binding studies with tritiated Ipriflavone showed the
      presence of a single specific binding site, wtih a Kd of about 70 nM and a
      binding capacity of 8 fmol/10(6) cells. These results demonstrate a direct effect
      of Ipriflavone and of Metabolite III on the human osteoclast precursor cell line
      FLG 29.1.

PMID- 7517665
TI  - Tyrosine phosphorylation of phospholipase C-gamma 2 is involved in the activation
      of phosphoinositide hydrolysis by Fc receptors in human neutrophils.
AB  - The stimulation of phosphoinositide hydrolysis by a number of agonists
      (phosphoinositide response) is a ubiquitous transmembrane signalling process for
      the regulation of several cell functions. Two mechanisms of activation have been
      identified that involve different phospholipases C: one regulated by G-proteins
      and another regulated by receptors having an intrinsic tyrosine kinase domain or
      that stimulate intracellular tyrosine kinase activity. This last mechanism is
      activated in several immunological cells, including lymphocytes, mastocytes, NK
      cells and monocytes, in response to agonists that bind antigen receptors, and
      receptors for IgE and IgG. In the present study, we have investigated the role of
      tyrosine phosphorylation in the stimulation of phosphoinositide hydrolysis
      mediated by Fc gamma Rs in human neutrophils. The results demonstrated that: 1)
      the activation of Fc gamma Rs with insoluble immune complexes (IIC) induced a
      tyrosine phosphorylation of several proteins that was dose-dependently inhibited
      by the tyrosine kinase inhibitor, genistein; 2) the activation of Fc gamma Rs
      caused a stimulation of phosphoinositide hydrolysis measured as [3H]inositol
      phosphates formation; 3) genistein depressed the activation of phosphoinositide
      hydrolysis; 4) among the several proteins that became tyrosine phosphorylated
      upon Fc gamma Rs activation by IIC, one 145 kDa protein was identified as PLC
      gamma 2, using a specific antiserum. The phosphorylation of PLC-gamma 2 was
      completely inhibited by genistein. These results demonstrate that the
      phosphoinositide response to activation of Fc gamma Rs involves the tyrosine
      phosphorylation of PLC-gamma 2.

PMID- 7517666
TI  - A new LIM protein containing an autoepitope homologous to "senescent cell
      antigen".
AB  - Autoantibody eluted from aged human red blood cells was used to immunoscreen a
      human fetal liver expression library and led to the isolation of a cDNA encoding
      a novel 35.8 kDa protein with five LIM domains. An autoepitope homologous to the
      "senescent cell antigen" on the red blood cell membrane anion exchange protein
      identified by Kay et al. (P.N.A.S. 87:5734, 1990) was present in the first zinc
      finger of the third LIM domain. The gene for this novel protein is highly
      conserved in vertebrates, and its 4.6 kb mRNA is widely expressed in human
      tissues. Recombinant autoantigens such as the one reported here have potential
      applications in vitro for the purification, identification and quantitation of
      autoantibodies, and in vivo for the removal of autoantibodies, increasing red
      blood cell lifespan and reducing the need for transfusion.

PMID- 7517667
TI  - Evidence that alpha-fetoprotein suppresses the immunological function in
      transgenic mice.
AB  - We examined the in vivo immunosuppressive effect of alpha-fetoprotein (AFP) by
      infection experiments with Listeria monocytogenes, a facultative intracellular
      pathogen, using transgenic mice that express and produce human AFP. The
      transgenic mice showed diminished ability to eliminate bacteria in the early
      stage of infection. In addition, the transgenic mice had significantly reduced
      production of IFN-gamma in their livers and sera and TNF in their spleens. These
      data indicate that AFP suppresses the production of the cytokines, IFN-gamma and
      TNF in NK cells and macrophages so that the mice could not eliminate the
      bacteria. This is the first report that AFP has an in vivo immunosuppressive
      effect on cytokine production related to the early host defense against infection
      by microorganisms.

PMID- 7517669
TI  - Common structural patterns of cytokine outer surfaces.
AB  - Schemes of the four-helix bundle surfaces of interleukin-2, -4, -5,
      granulocyte/macrophage-, granulocyte-, macrophage-colony-stimulating factor,
      interferon-beta, -gamma and growth hormone were designed. All cytokines appeared
      to have the structurally similar "holes" on the surfaces. They were suggested to
      serve as a part of the main receptor-binding sites.

PMID- 7517670
TI  - Calyculin A, okadaic acid and W-7 interfere with a distal step in pancreatic
      acinar signal transduction.
AB  - The effects of the serine/threonine phosphatase inhibitors calyculin A, okadaic
      acid and the calmodulin antagonist W-7 on amylase secretion were studied in
      pancreatic acini. Calyculin A and okadaic acid dose-dependently inhibited amylase
      secretion to basal levels when stimulated with the intracellularly acting
      secretagogues thapsigargin, 8-br-cAMP or PMA. W-7 dose-dependently inhibited
      thapsigargin- or 8-br-cAMP-induced amylase secretion. In combination,
      thapsigargin, 8-br-cAMP and PMA induced amylase secretion comparable to the
      stimulation by cholecystokinin. Their effect was significantly inhibited by
      calyculin A, okadaic acid or W-7. These data imply that type 1- and 2b
      phosphatases and calmodulin play a key role in the stimulation of exocrine
      pancreatic secretion at a distal step of both the Ca2+/IP3- and cAMP-mediated
      signal-transduction pathways.

PMID- 7517668
TI  - Sensitivity of (138 Glu-->Lys) mutated human immunodeficiency virus type 1 (HIV
      1) reverse transcriptase (RT) to HIV-1-specific RT inhibitors.
AB  - Human immunodeficiency virus type 1 (HIV-1) recombinant reverse transcriptase
      (RT) containing lysine (Lys) instead of glutamic acid (Glu) at position 138
      proved fully resistant to the inhibitory effect of TSAO derivatives, but retained
      marked sensitivity to all other HIV-1-specific inhibitors investigated. In
      contrast, 181 Tyr-->Cys mutated RT lost sensitivity to all HIV-1-specific
      inhibitors. There was a close correlation between the sensitivity/resistance
      pattern of HIV-1-specific inhibitors against mutated (138 Glu-->Lys) recombinant
      HIV-1 RT and mutant virus strains selected for resistance against TSAO-m3T in
      cell culture and proven to contain the 138-Lys mutation as the sole mutation
      within the amino acid 50-270 region of their RT.

PMID- 7517673
TI  - Antisense src expression inhibits proliferation and erythropoietin-induced
      erythroid differentiation of K562 human leukemia cells.
AB  - We constructed a recombinant plasmid which expresses antisense src RNA in human
      cells and used it as a tool for investigating the role of pp60c-src in
      proliferation and differentiation of K562 human leukemia cells. In erythropoietin
      (EPO)-responsive cells, EPO induces rapid tyrosine phosphorylation of several
      cellular proteins including EPO receptor (EPOR) although EPOR has no tyrosine
      kinase domain. Here we show that antisense src RNA expression suppresses pp60c
      src synthesis in the recombinant plasmid-transfected K562 cells, reduces the
      proliferation and inhibits hemoglobin synthesis and glycophorin A expression
      promoted by EPO in K562 cells. These findings suggest that pp60c-src plays
      crucial roles in the proliferation and EPO-induced erythroid differentiation of
      K562 cells.

PMID- 7517672
TI  - Increased coexpression of CFTR and S100 calcium binding proteins MRP8 and MRP14
      mRNAs in cystic fibrosis human tracheal gland cells.
AB  - We have demonstrated for the first time, by Northern analysis, the presence of
      the S-100 calcium binding proteins MRP8 (also called "cystic fibrosis protein")
      and MRP14 mRNAs in cultured human tracheal gland cells, obtained from normal and
      cystic fibrosis (CF) patients. A significant increase of these mRNAs in cells of
      CF origin (as well as that of CFTR mRNA) is shown. These results allow us to
      assume a potential pretranslational regulation of MRP8 and MRP14 gene expression
      related to the presence of a mutated CFTR gene.

PMID- 7517671
TI  - Regulation of cholecystokinin secretion by calcium-dependent calmodulin kinase
      II: differential effects of phenylalanine and cAMP.
AB  - The release of cholecystokinin was investigated in STC-1 cells, an intestinal
      cholecystokinin-secreting cell line. Fifteen minute incubation of cells with the
      amino acid, L-phenylalanine (20 mM), or the phosphodiesterase inhibitor, IBMX
      (100 microM), stimulated cholecystokinin secretion. Stimulation of secretion by
      both agents was associated with an increase in cytosolic calcium and was
      inhibited by the calcium channel blocker, diltiazem (10 microM). The calcium
      calmodulin kinase II inhibitor, KN-65 (1.4 microM), markedly reduced IBMX
      stimulated secretion, but had no effect on phenylalanine-mediated activity. KN-62
      also inhibited IBMX-induced increases in cytosolic calcium, suggesting that cAMP
      may activate diltiazem-sensitive calcium channels by a calmodulin-dependent
      process.

PMID- 7517674
TI  - BiP is a substrate for src kinase in vitro.
AB  - In a study to investigate the ability of chaperones to modulate src kinase
      activity, it was observed that BiP, a member of the HSP70 family found in the
      endoplasmic reticulum, is an excellent substrate for src kinase in vitro. The
      reaction requires polylysine and the results suggest that two tyrosine residues
      are phosphorylated. Although there is no evidence for this reaction in vivo, it
      does provide a very efficient method to label BiP.

PMID- 7517675
TI  - Tenascin distribution in articular cartilage from normal subjects and from
      patients with osteoarthritis and rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether tenascin is present in normal and diseased human
      cartilage. METHODS: Immunohistochemical and biochemical assays with a monoclonal
      antibody against all tenascin isoforms (BC-4) were used. RESULTS: Cartilage
      samples from osteoarthritis and rheumatoid arthritis patients contained increased
      amounts of tenascin compared with the levels in normal cartilage. Human fetal
      cartilage was also found to contain tenascin. In normal cartilage explants
      treated with interleukin-1 beta, tenascin was present in pericellular areas of
      all layers. Immunolocalization studies revealed that tenascin was most abundant
      in the superficial layers of osteoarthritic cartilage. Western blot analysis
      performed from dissociative extracts of diseased cartilage confirmed the presence
      of subunits of the native molecule. CONCLUSION: Tenascin is increased in
      arthritic cartilage and is weakly expressed in normal cartilage.

PMID- 7517676
TI  - N-monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the
      development of adjuvant arthritis in rats.
AB  - OBJECTIVE: To test the hypothesis that nitric oxide (NO) is involved in the
      pathophysiology of arthritis. METHODS: Arthritis was induced in male Lewis rats
      by the injection of adjuvant into the base of the tail. The NO synthase (NOS)
      inhibitor, NG-monomethyl-L-arginine (L-NMA), was administered daily by the oral
      route for 19 days. Paw swelling, plasma fibrinogen levels, and urinary NO2/NO3
      levels were measured to assess the effect of L-NMA on the arthritic response and
      whole-body NO production, respectively. On day 20, the ankle joints were
      processed for histopathologic evaluation. RESULTS: The onset of clinical symptoms
      was preceded by elevated biosynthesis of NO. In a dose-dependent manner, L-NMA
      inhibited both NO biosynthesis and paw swelling; histopathologic changes in the
      ankle joints were also prevented. D-NMA had no effect on the development of
      arthritis, while L-arginine reversed the effects of L-NMA. Fibrinogen levels in
      rats with arthritis were unaffected by L-NMA. CONCLUSION: NO is critical to the
      development of both the inflammatory and erosive components of adjuvant arthritis
      in rats. There may be a future clinical role for suitable inhibitors of NO
      production or activity.

PMID- 7517678
TI  - Expression of Clara cell 10-kD gene in the human endometrium and its relationship
      to ovarian menstrual cycle.
AB  - Clara cell 10-kD (cc10-kD) protein has been suggested to be the human counterpart
      of rabbit uteroglobin (UG). Like UG, this protein is also a potent inhibitor of
      phospholipase A2 (PLA2) and a substrate of transglutaminase. Although it has been
      established that UG gene expression in the rabbit endometrium is stimulated by
      progesterone, the expression of cc10-kD gene in the human endometrium is not
      clearly understood. The present study was undertaken to determine whether the
      cc10-kD gene is expressed in the human endometrium and whether its level of
      expression changes in relation to the ovarian menstrual cycle. Using reverse
      transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence, we
      demonstrate that the cc10-kD gene is expressed in different stages of the
      menstrual cycle and that the highest level of expression is reached during the
      luteal phase. These results suggest that like rabbit UG, cc10-kD gene expression
      in the human endometrium may be stimulated by progesterone. Since cc10-kD is a
      potent inhibitor of PLA2 activity, this protein may play an important
      physiological role in regulating eicosanoid levels in the human uterus.

PMID- 7517677
TI  - Serotonin neurotoxicity after (+/-)3,4-methylenedioxymethamphetamine (MDMA;
      "Ecstasy"): a controlled study in humans.
AB  - (+/-)3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy"), an increasingly popular
      recreational drug, is known to damage brain serotonin 5-hydroxytryptamine (5-HT)
      neurons in experimental animals. Whether MDMA is neurotoxic in humans has not
      been established. Thirty MDMA users and 28 controls were admitted to a controlled
      inpatient setting for measurement of biologic and behavioral indexes of central 5
      HT function. Outcome measures obtained after at least 2 weeks of drug abstinence
      included concentrations of monoamine metabolites in cerebrospinal fluid (CSF),
      prolactin responses to L-tryptophan, nociceptive responses to ischemic pain, and
      personality characteristics in which 5-HT has been implicated (i.e., impulsivity
      and aggression). Subjects with a history of MDMA exposure had lower levels of CSF
      5-hydroxyindoleacetic acid (the major metabolite of 5-HT) than controls (p =
      .001). Although they resembled controls in their prolactin response to L
      tryptophan and their response to ischemic pain, MDMA users had lower scores on
      personality measures of impulsivity (p = .004) and indirect hostility (p = .009).
      The CSF findings suggest that 5-HT neurotoxicity may be a potential complication
      of MDMA use. Further, differences in personality support the view that 5-HT
      systems are involved in modulating impulsive and aggressive personality traits.
      Additional studies of MDMA-exposed individuals are needed to confirm and extend
      the present findings. Such studies could help elucidate the role of 5-HT in
      normal brain function as well as in neuropsychiatric disease states.

PMID- 7517679
TI  - Antibodies specific for the neuronal form of the Src protein elicited by an
      antigenized antibody.
AB  - To elicit antibodies directed specifically against the neuron-specific form of
      the c-src gene product, pp60c-src(+), we used an antigenized antibody comprising
      a decamer containing the amino acid sequence specific to pp60c-src(+) inserted
      into the third hypervariable loop of the heavy (H)-chain variable (V)-region.
      This was used to raise anti-idiotype antibodies reacting with the peptide epitope
      in rabbits. The antisera reacted with pp60c-src(+), as judged by immune blotting,
      immunoprecipitation, immune complex kinase assay, and indirect immunofluorescence
      staining, but did not react with the fibroblast form of the c-src gene product,
      pp60c-src. Antigenized antibody is a useful approach for producing antibodies
      able to distinguish between isoforms of the same gene product and specific for
      the neuronal form of the Src protein.

PMID- 7517680
TI  - Complete structure and expression of the rat alpha B-crystallin gene.
AB  - alpha B-Crystallin, a member of the small heat shock family of proteins, is
      synthesized as a component of various developmental programs, in response to
      stress and in a number of pathological states. We have determined the complete
      structure of the alpha B-crystallin gene (6,806 bp encompassing 2,299 bp upstream
      from ATG and 859 bp at the 3' end, past the first polyadenylation signal).
      Comparison of the rat and the human alpha B-crystallin genes reveals significant
      conservation of the nucleotide sequences in almost all regions except in intron
      2. The 1-kb region immediately upstream of ATG shows about 75% overall homology.
      A 78-bp sequence in the intron 1 and sequences in the 3' untranslated region show
      about 95% and 85% sequence identity, respectively. Characterization of the
      expression of this gene in different tissues in the rat by extensive analyses,
      utilizing primer extension. RNase protection, and rapid amplification of cDNA
      ends (RACE) revealed a predominant transcription initiation site 44 bp upstream
      of ATG. Northern analyses with "coding-only" and upstream "noncoding" probes did
      not support the thesis that heterogeneity in the alpha B-crystallin mRNAs arises
      from variations in the sequences immediately upstream of the predominant
      transcription initiation site. Importantly, the known relative levels of alpha B
      crystallin protein in different tissues correlate best with the presence of
      transcripts starting from this initiation site.

PMID- 7517681
TI  - Establishment of a human malignant T lymphoma cell line carrying retrovirus-like
      particles with RT activity.
AB  - We have established an IL-2 independent malignant lymphoma line (CM-1) from
      peripheral T lymphocytes donated by a female patient with nervous system disease,
      the biological characteristics of CM-1 cells was studied in this paper. Another T
      lymphocytes, such as peripheral T lymphocytes donated by a male patient with
      multiple sclerosis, could be transformed into a malignant lymphoma line by using
      filtered supernatant of the CM-1 cultured medium, thus the CM-2 cell line was
      established. The CM-1 and CM-2 cells were transplanted by subcutaneous
      inoculation into nude mice, and could cause the occurrence of typical malignant
      lymphoma. The observation of electron micrographs suggested the existence of
      virions in the CM-1 and CM-2 cells, and these virions were similar to retrovirus
      in the ultra-structure characteristics. It was found that this virus possesses
      reverse transcriptase activity. Results obtained from serological assay,
      molecular hybridization and PCR excluded the existence of other human viruses,
      which were commonly used in our laboratory. The unknown virus possesses strong
      transformation activity, and probably is a new retrovirus. Meanwhile, the work on
      the clone and sequence analysis of this virus are being carried out.

PMID- 7517682
TI  - Is mastocytosis a mast cell neoplasia or a reactive hyperplasia? Clues from the
      study of mast cell growth factor.

PMID- 7517684
TI  - Overlapping protection in the ribonuclease protection assay due to complementary
      vector sequences.

PMID- 7517685
TI  - RT-PCR assay for detection of transcripts from very few cells using whole cell
      lysates.

PMID- 7517686
TI  - From RNA to sequenced clones within three days: a complete protocol.
AB  - Detection of specific mRNA transcripts by the reverse transcription/polymerase
      chain reaction (RT/PCR) technique has become increasingly important. The
      technique is fast and has a very high resolution. Cloning of these PCR fragments
      into vectors is sometimes necessary for identification of alternative splicing
      products, for bacterial expression or for generation of a DNA probe. Here we
      present a complete protocol for RT/PCR, cloning and sequencing of PCR, cloning
      and sequencing of PCR products beginning with the total RNA and ending with the
      DNA sequence within three days. To illustrate the procedure as an example, a
      fragment of the human glyceraldehyde-3-phosphate dehydrogenase mRNA was amplified
      from total RNA, cloned and partially sequenced. The protocol has been optimized
      for small scale to facilitate handling and to reduce costs.

PMID- 7517687
TI  - The isolation of differentially expressed genes in fibroblast growth factor
      stimulated BC3H1 cells by subtractive hybridization.
AB  - We have developed a subtractive hybridization procedure based on the
      hybridization of a single-stranded phagemid cDNA library (target) to biotinylated
      RNA (driver). We have applied this method to fibroblast growth factor (FGF)
      induced-uninduced mouse brain tumor-derived muscle-like cell. BC3Hl cDNA
      libraries. After hybridization to a C(o)t value of 1000, cDNAs common to the
      target and driver populations were subtracted up to 231-fold, whereas several
      highly induced genes were enriched from 2-15-fold. Interestingly, moderately
      induced genes (e.g., the 12-fold-induced nur/77 gene) were subtracted even at a
      low C(o)t value of 50. Therefore, at every C(o)t tested, subtractive
      hybridization tended to equalize the uninduced and moderately induced common
      sequences within target populations regardless of the abundance of the gene
      species. These observations suggest that subtractive hybridization should only be
      used for identifying target genes that are either uniquely expressed or highly
      induced.

PMID- 7517683
TI  - Proliferating cell nuclear antigen counts as markers of cell proliferation in
      head and neck cancer.
AB  - Proliferating cell nuclear antigen (PCNA) expression was investigated
      immunhistochemically in 53 squamous cell carcinomas of the head and neck. PCNA is
      a 36-kDa nuclear protein associated with the cell cycle. Results were compared
      with Ki67 counts, with this latter marker used to demonstrate proliferative
      compartments. Overall, the PCNA and Ki67 labelling index showed a similar
      distribution pattern in normal and tumor tissue. A strong correlation was found
      to histological differentiation. There was no significant difference between PCNA
      and Ki67 counts (r = 0.8), and PCNA immunostaining allowed assessment of
      proliferative activity in the head and neck cancers studied. The application of
      formalin-fixed, paraffin-embedded tumor material demonstrated the advantage of
      this method and showed that it is an excellent alternative to Ki67 counts.

PMID- 7517688
TI  - Protein kinase regulation: insights from crystal structure analysis.
AB  - The crystal structures of three protein kinases in various states of activity
      have recently been determined. Analysis of these structures is providing
      unprecedented insight into the precise atomic movements underlying protein kinase
      regulation.

PMID- 7517689
TI  - Spatial and temporal signalling by calcium.
AB  - Recent research has shown the importance of the spatial and temporal aspects of
      calcium signals, which depend upon regenerative properties of the inositol
      trisphosphate and ryanodine receptors that regulate the release of calcium from
      internal stores. Initiation sites have been found to spontaneously release
      calcium, recognized as 'hot spots' or 'sparks', and can trigger a wave that
      spreads through a process of calcium-induced calcium release.

PMID- 7517690
TI  - [A 85-year-old right-handed woman with aphasia and left hemiparesis].
AB  - We report a 85-year-old woman who developed speech disturbance and left
      hemiparesis. She had a gradual onset of gait disturbance 3 years prior to the
      present admission. Five days before admission, she started to pace up and down in
      her house; she did not want to take food on the following day, and she developed
      fever of 39 degrees C; it was also noted that she became mute. On the next day,
      she developed left hemiparesis; she was still mute but was able to communicate by
      hand writing to some extent. She was admitted to our service on February 24,
      1992. On admission, she was alert but mute; her body temperature was 37.1 degrees
      C, and her BP 110/70 mmHg. The lungs were clear and general physical examination
      was unremarkable. Neurologic examination revealed that she did not utter even a
      word. She was unable to understand examiner's simple questions; communication by
      hand writing was also difficult, but she could draw her name and a circle;
      repetition was also impaired. Examination of other higher cerebral functions such
      as praxis and gnosis was impossible. Her optic fundi were unremarkable; no
      anisocoria was noted; extraocular muscles appeared intact, and the vestibulo
      ocular reflex was normally elicited. The nasolabial fold was shallower on the
      left; the tongue showed a slight deviation to the left. She had near complete
      spastic left hemiplegia; deep tendon reflexes were increased
      bilaterally.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517691
TI  - Polyarthralgia and amenorrhea as a complication of intrathecally infused morphine
      and Dilaudid in the treatment of chronic benign back pain.

PMID- 7517692
TI  - Establishment and characterization of a novel immature T-ALL cell line, UHKT-42,
      with TCR beta/delta expression.
AB  - A novel immature human T-ALL cell line, UHKT-42, was established from a 12 year
      old male patient with acute undifferentiated leukemia. The cell line expressed
      surface CD7, CD5 and cytoplasmic CD3 antigens. All other T-lymphocytic antigens
      were undetectable on the surface or in the cytoplasm of cultured cells.
      Expression of the T-cell receptor (TCR) beta, TCR delta, CD3 delta and CD3
      epsilon genes was detected by Northern blotting in total cellular RNA extracts,
      however, the expression of TCR alpha and TCR gamma was undetectable. After
      stimulation by TPA for 3 days, only the appearance of CD25 (Tac antigen) was
      detected by immunofluorescence and flow cytometry. Secretion of interleukin-2 (IL
      2) into the culture media was also detected after stimulation by PHA or TPA, but
      not in unstimulated cells. These results suggest that UHKT-42 cells are early
      precursors of T cells, with TCR beta/delta expression.

PMID- 7517694
TI  - Immunogenicity and protective efficacy of solubilized merozoite-enriched
      Theileria sergenti immunogens. III. Characterization of immunodominant peptides.
AB  - Immunoblot analysis utilizing bovine sera from naturally or experimentally
      infected with Theileria sergenti were used to determine the immunodominant
      polypeptides of T. sergenti (Korean isolate). The previously recognized major
      bands, 18 kDa, 29 kDa, 34 kDa and 45 kDa, were excised after electrophoresis and
      transfer to PVDF membrane. The individual bands were sequenced. The 34 kDa
      polypeptide which was the most antigenic and immunogenic peptide was observed in
      the Western blot. However, Chou-Fasman prediction sites (antigenic site) for
      antigen determinants of the 45 kDa, 24 kDa, 29 kDa and 18 kDa polypeptide were 6,
      4, 2 and 0, respectively. However, the 45 kDa polypeptide showed no reaction with
      anti-T, sergenti hyperimmune serum.

PMID- 7517693
TI  - Fibroblast attachment to Arg-Gly-Asp peptide-immobilized poly(gamma-methyl L
      glutamate).
AB  - The attachment of MRC-5 human fibroblasts was investigated on poly(gamma-methyl L
      glutamate) (PMLG), and upon cell adhesion peptides Arg-Gly-Asp-Ser (RGDS)- and
      Gly-Arg-Gly-Asp-Ser (GRGDS)-immobilized PMLG (RGDS-PMLG and GRGDS-PMLG). The
      peptides were immobilized by their N-terminal amine to activated PMLG surfaces.
      Prior to peptide immobilization, the aminolysis of PMLG surfaces was performed
      with hydrazine hydrate (HA), ethylenediamine (EDA), and hexamethylenediamine
      (HMDA) and was followed by the activation with hexamethylene diisocyanate.
      Surface characterization of these films was carried out by means of a Fourier
      transform IR (FT-IR) spectrometer equipped with an attenuated total reflectance
      (ATR) attachment. The amount of immobilized RGDS could be controlled by the
      reaction time of the aminolysis. The effects of HA, EDA, and HMDA as a spacer on
      the cell attachment were also investigated, and it was suggested that a longer
      spacer promoted the cell attachment via specific receptor-ligand interaction.

PMID- 7517696
TI  - Is laparatomy the first step in treatment of childhood liver tumors?--The
      experience from the German Cooperative Pediatric Liver Tumor Study HB-89.
AB  - In the cooperative study on childhood liver tumors (HB-89) of the German Society
      for Pediatric Oncology and Hematology an initial laparotomy was recommended for
      all children with a primary liver tumor. Now a more differentiated surgical
      strategy has been worked out on the basis of study data. Patient's age, alpha
      fetoprotein or other tumor markers, imaging techniques and histological
      investigations were predictive for differential diagnosis in most, but not all
      cases. Surgical complications occurred infrequently, there was no perioperative
      mortality. Results of therapy were satisfactory in hepatoblastoma, but poor in
      hepatocellular carcinoma, since chemotherapy and radiation were not effective on
      this tumor. In conclusion, primary chemotherapy without histological confirmation
      is justified, if in children between six months and three years of age with a
      high serum-alpha-fetoprotein a hepatoblastoma is certain, and the tumor involves
      both lobes of the liver. All other patients should have an initial laparotomy for
      resection of small or biopsy of large tumors. In case of hepatocellular carcinoma
      a primary resection should be attempted on principle.

PMID- 7517695
TI  - Expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell
      adhesion molecule-1 (VCAM-1) on proliferating vascular endothelial cells in
      diabetic epiretinal membranes.
AB  - The present study demonstrated the expression of intercellular adhesion molecule
      1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), the proliferating
      status of the neovascular endothelial cells, and the activation of vascular
      endothelial cells bearing the two cell adhesion molecules in diabetic epiretinal
      membranes by using double immunofluorescence and APAAP techniques. The results
      showed that ICAM-1 was detected in 36 out of 40 (90%) proliferative diabetic
      retinopathy epiretinal membranes, VCAM-1 was found in 32 out of 40 cases (80%);
      in 21 out of 26 (81%) vascularised membranes the endothelial cells of the new
      vessels in the membranes were still in a proliferative stage (positive for
      proliferating endothelial cell marker EN 7/44) and, further, in 20 out of 26
      cases (77%) ICAM-1 was detected on the proliferating endothelial cells and VCAM-1
      was found in 21 cases (81%). The expression of cell adhesion molecules,
      especially ICAM-1 and VCAM-1 in diabetic epiretinal membranes suggests that cell
      to cell interactions may play a significant role in the development of PDR
      membranes. In particular, the expression of ICAM-1 and VCAM-1 on proliferating
      endothelial cells indicates the activation of these cells, which is the first
      critical step for lymphocyte/endothelial cell interactions and the initiation of
      immune responses. The significance of proliferating status of the
      neovascularisation in the membranes may be related to the clinical course and
      prognosis of the disease.

PMID- 7517697
TI  - N9 neuraminidase complexes with antibodies NC41 and NC10: empirical free energy
      calculations capture specificity trends observed with mutant binding data.
AB  - X-ray crystallographic coordinates of influenza virus N9 neuraminidase complexed
      with monoclonal antibodies NC41 and NC10 [Tulip et al. (1992) J. Mol. Biol. 227,
      122-148] served as a starting point for calculations aimed at estimating free
      energy changes (delta G) of complex formation between the two antibodies and the
      neuraminidase. Using an empirical function incorporating hydrophobic,
      electrostatic, and conformational entropy effects, we estimated contributions
      individual neuraminidase residues make to complex formation (delta G(residue))
      and compared the calculated values to experimentally measured differences in
      antibody binding between the wild-type and mutated neuraminidases [Nuss et al.
      (1993) Proteins 15, 121-132; calculations done without prior knowledge of the
      experimental data]. A good correspondence was found between the calculated delta
      G(residue) values and the mutant binding data in that side chains with large
      calculated delta G contributions (delta G(residue) < -1 kcal/mol) lie at sites of
      mutation which cause a marked reduction in antibody binding, and side chains for
      which delta G(residue) > -1 kcal/mol are sites at which a mutation does not have
      a marked effect on binding. Because most of the delta G(residue) < -1 kcal/mol
      side chains also make hydrogen bonds/salt bridges with the antibody, the
      correspondence of the effect of antibody binding with these electrostatic
      interactions (18 out of 27 for NC41 and, tentatively, 5 out of 7 for NC10) is
      about as good as that with predicted energetic residues. All the delta G(residue)
      < -1 kcal/mol neuraminidase side chains cluster around the most protruding
      surface regions and are thus spread over different epitope segments.
      Surprisingly, different residues were found to make the most critical
      contributions to the NC41 and NC10 complex stabilities despite the fact that the
      NC41 and NC10 antigenic epitopes overlap, having approximately 70% of surface
      residues in common. It is thus possible, for two different antibodies, to
      recognize the same protein surface in strikingly different ways. As only a
      fraction of the neuraminidase residues appear to make large contributions to
      antibody binding, the results also support the hypothesis of a "functional"
      epitope in antigen-antibody interactions. Positive trends between both backbone
      rigidity and residue accessibility in the complexed state, and contributions of
      these residues to binding, were also observed for the NC41 complex.

PMID- 7517698
TI  - Interaction of immobilized recombinant mouse C-type macrophage lectin with
      glycopeptides and oligosaccharides.
AB  - Inflammatory and tumoricidal macrophages express galactose- and N
      acetylgalactosamine-specific Ca(2+)-dependent lectins on their surfaces. This
      lectin is a family member of membrane-bound C-type animal lectins and consists of
      304 amino acid residues (molecular weight 34,595). In the present study,
      expression vectors containing a nucleotide sequence corresponding to the
      carbohydrate-binding domain of mouse macrophage lectin cDNA have been prepared.
      The carbohydrate-binding specificity of the recombinant macrophage lectin
      expressed in Escherichia coli was investigated by comparing elution profiles of
      various glycopeptides having defined carbohydrate structures on immobilized
      lectins. When elution profiles of high mannose-type and complex-type Asn-linked
      carbohydrate chains were compared, the degree of retardation from immobilized
      macrophage lectin column was in the order tetraantennary complex-type with
      terminal galactosyl residues > triantennary complex-type with terminal galactosyl
      residues > biantennary complex-type with terminal galactosyl residues > high
      mannose-type glycopeptides. N-Terminal octapeptides from human glycophorin A that
      bore three NeuAc alpha 2-3Gal beta 1-3(NeuAc alpha 2-6)GalNAc serine/threonine
      linked tetrasaccharide chains and their sequentially deglycosylated derivatives
      were also applied to this column. Glycopeptides carrying three constitutive
      GalNAc-Ser/Thr(Tn-antigen) had the strongest affinity, whereas those with fully
      sialylated carbohydrate tetrasaccharide chains showed weak interaction. The
      association kinetics of Asn-linked glycopeptides from bovine asialofetuin to
      recombinant macrophage lectin was determined by surface plasmon resonance
      spectroscopy. The results indicate k(assoc) value of 1.63 x 10(4) M-1 s-1. The
      calculated value for Ka was 6.20 x 10(7) M.

PMID- 7517699
TI  - High incidence of uterine inversion in mast cell-deficient osteopetrotic mutant
      mice of mi/mi genotype.
AB  - Mutations at either W or mi (microphthalmia) loci in the mouse can lead to a
      deficiency in melanocytes and mast cells. In addition, W mutants can be anemic
      and sterile, whereas mi mice are osteopetrotic because of a
      monocyte/macrophage/osteoclast defect. Since c-kit receptor tyrosine kinase is
      the gene product of the W locus and mi mutation has been suggested to affect the
      transduction of signals from the c-kit and c-fms receptors, we here examined the
      effect of mi mutation on fertility. Testes and ovaries from mi/mi mice were
      histologically normal, and the pattern of c-kit protein expression was not
      different from that of +/+ mice. Homozygous mutant crosses (mi/mi x mi/mi) were
      fertile, but inversion of the uterus occurred in 86% of the deliveries. In some
      cases, the placenta was found still attached to the inverted uterus after
      delivery. Decidual cells were present and expressed c-kit protein normally in the
      placenta of mi/mi mice. The inversion was also observed in mi/mi females mated to
      +/+ males. No uterine inversion was noted when +/mi females were crossed with
      mi/mi or +/mi males, suggesting that the genotype of the mother but not of the
      father or fetus is important for the pathogenesis. The numbers and body weights
      of mi/mi newborns were less than those of +/mi littermates. Mast cells were
      absent, but c-kit-positive cells were present, in the uterine muscle layers of
      pregnant mi/mi mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517700
TI  - Insulin-like growth factor I (IGF-I), IGF-I receptors, and IGF binding proteins 1
      4 in human uterine tissue: tissue localization and IGF-I action in endometrial
      stromal and myometrial smooth muscle cells in vitro.
AB  - The objective of the present study was to elucidate the presence and cellular
      distribution of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR),
      and IGF binding proteins (IGFBPs) in human uterine tissue at various reproductive
      stages, and to determine the effect of IGF-I and its interaction with epidermal
      growth factor (EGF) and platelet-derived growth factor (PDGF) in endometrial
      stromal and myometrial smooth muscle cells in primary culture. Using specific
      antibodies, immunohistochemical observations indicated that luminal and glandular
      epithelial cells were the major sites of immunoreactive IGF-I, IGF-IR, and IGFBPs
      1-4, followed by myometrial smooth muscle and endometrial stromal cells. The
      immunostaining intensity of IGF-I, IGF-IR, and IGFBPs in endometrial but not
      myometrial tissue was cycle-dependent and higher in the late proliferative and
      early/mid-secretory periods than in the late secretory and postmenopausal
      periods, with little immunostaining at the early proliferative phase of the
      menstrual cycle. Stromal and smooth cells in primary cell culture also contained
      immunoreactive IGF-I, IGF-IR, and IGFBPs. IGF-I at 10-100 ng/ml stimulated 3H
      thymidine incorporation in quiescent stromal and smooth muscle cells with maximal
      effect at 100 ng/ml (p < 0.05). However, in the presence of 2% serum, which
      induces half-maximal stimulation, IGF-I (100 ng/ml) further increased the rate of
      3H-thymidine incorporation in stromal but not smooth muscle cells (p < 0.05). The
      effect of IGF-I was significantly lower than that induced by EGF (10 ng/ml), PDGF
      BB (10 ng/ml) and their combination (p < 0.005), and higher in stromal cells from
      proliferative, than secretory phase of the cycle in the presence of 2% fetal
      bovine serum, but not serum-free condition (p < 0.005). The effect of IGF-I on
      myometrial smooth muscle cells was significantly higher than that induced by EGF,
      but lower than that induced by PDGF-BB or by EGF+PDGF-BB, without the cycle
      specificity seen with stromal cells. EGF, PDGF-BB, and their combination with IGF
      I, but not IGF-I alone, stimulated stromal and smooth muscle cell growth as
      determined by a cell proliferation assay. The results indicate that human uterine
      tissue at various reproductive stages contains immunoreactive IGF-I, IGF-IR, and
      IGFBPs 1-4. Although IGF-I alone was found to be a weak mitogenic factor for
      stromal and smooth muscle cells, by interacting with EGF and PDGF-BB in a cycle
      dependent manner it may regulate the growth and differentiation of these and
      other uterine cell types.

PMID- 7517701
TI  - Opposing effects on modulation of angiogenesis by protein kinase C and cAMP
      mediated pathways.
AB  - The role of cAMP-mediated pathway in modulating angiogenesis was investigated. We
      have shown previously that activators of protein kinase C (PKC) caused a marked
      increase in angiogenesis, while the specific inhibitor of PKC, Ro 318220
      suppressed angiogenesis. Here we show that forskolin, which activates adenylate
      cyclase and elevates the intracellular levels of cAMP, and the Sp-diastereomer of
      adenosine cyclic-3',5'-monophosphothioate (Sp-cAMPS), caused a dose-dependent
      suppression of collagenous protein biosynthesis and angiogenesis in the chick
      chorioallantoic membrane system (CAM). The opposite modulation of angiogenesis by
      activators of PKC and elevated cAMP levels was further confirmed by the
      suppression of 4 beta-phorbol-12-myristate-13-acetate (4 beta-PMA)-stimulated
      angiogenesis by either forskolin or Sp-cAMPS. On the contrary, the Rp
      diastereomer of adenosine cyclic-3',5'-monophosphothioate (Rp-cAMPS), which
      antagonises endogenous cAMP biochemical actions, had no effect on angiogenesis
      alone and did not suppress 4 beta-PMA stimulated angiogenesis. However, Rp-cAMPS
      antagonised the effect of forskolin and Sp-cAMPS on 4 beta-PMA induced
      angiogenesis. Similar results were obtained in the human umbilical vein
      endothelial cell tube formation assay. In this system, the PKC inhibitor, Ro
      318220, caused a dose-dependent inhibition of 4 beta-PMA reversed this effect.
      Also, forskolin and Sp-cAMPS caused an inhibition in tube formation. These
      results indicate that increased levels of intracellular cAMP have a negative
      effect in normal angiogenesis and cause a large reduction of the promotion of
      angiogenesis resulting from PKC activation.

PMID- 7517703
TI  - Growth characteristics of cultured human macrovascular venous and arterial and
      microvascular endothelial cells.
AB  - The morphological and growth characteristics of human macrovascular endothelial
      cells (ECs) from venous and arterial umbilical cord vessels and microvascular ECs
      from foreskin were compared during cultivation. By means of time-lapse
      microcinematography and phase-contrast microscopy, differences in cell morphology
      and migratory activity between the different types of ECs were found. Growth
      characteristics were dependent on the type of EC, the nature of the substrates on
      which the ECs were grown and the presence of growth factors. For all types of ECs
      optimal growth and formation of a monolayer were observed when the ECs were
      cultured on fibronectin or gelatin substrates in the presence of EC growth factor
      and heparin. Under these conditions confluent cultures of macrovascular ECs
      reached maximal cell densities of 1,400-1,900 ECs/mm2, whereas microvascular ECs
      reached maximal cell densities of about 700-900 ECs/mm2. The cell cycle times
      calculated from the population-doubling time and the stathmokinetic index,
      respectively, amounted to 63 and 83 h for microvascular ECs, 33 and 35 h for
      venous macrovascular ECs, and 29 and 35 h for arterial macrovascular ECs.

PMID- 7517702
TI  - Neovascularization of embryonic rat hearts cultured in oculo closely mimics in
      utero coronary vessel development.
AB  - Coronary neovascularization was studied following grafting of avascular hearts
      from gestation day-12 (E-12) rat embryos to the anterior eye chambers of adult
      rats. Volume densities (Vv) of vessels, myocytes, and the extracellular matrix
      (ECM) after 3-7, 14, 21, and 35 days in oculo were compared to Vv in hearts
      developing in utero at E-15, E-18, and E-20. The myocardium in both models
      exhibited similar vessel Vv and capillary developmental stages: (1) clustering of
      endothelial cells and red blood cells; (2) endothelial cell migration, and (3)
      tube formation/maturation. The Vv of myocytes increased while that of the ECM
      remained constant over time. Cross-species grafting utilizing species-specific
      antibodies determined that the majority, but not all, of the 10-day graft
      vasculature was of graft origin. Therefore, both de novo growth (vasculogenesis)
      and sprouting (angiogenesis) were occurring in oculo. Tracer molecules infused
      into host rats reached the outermost graft vessels only after 10 days in oculo,
      suggesting a functional link with the host circulation after this time. Thus, we
      have shown that both models exhibit similar: (1) vascular Vv; (2) shifts in Vv of
      nonvascular components; (3) stages of neovascularization, and (4) mechanisms of
      neovascularization. In conclusion, coronary neovascularization occurring in oculo
      closely mimics normal coronary vessel development.

PMID- 7517705
TI  - Autoantibodies to IGF-1 binding sites in thyroid associated ophthalmopathy.
AB  - Graves' disease is an autoimmune disorder but the nature of the association
      between hyperthyroidism and ophthalmopathy is not yet understood. Serum
      autoantibodies to orbital tissues have previously been identified and the cross
      reactivity with orbital and thyroid antigens has been implicated in the
      development of thyroid-associated ophthalmopathy (TAO). The ophthalmopathy of
      Graves' disease is remarkable for the hypertrophy of extraocular muscles and
      proliferation of fibroblasts within the orbit; features which suggest a possible
      involvement of growth factors. The present study was therefore undertaken to
      investigate the interaction of IgGs extracted from the sera of patients with
      Graves' disease, with or without overt ophthalmopathy, with respect to IGF-1
      receptor binding sites on fibroblasts from human orbital tissue. IGF-1 binding
      sites were demonstrated on human orbital fibroblast monolayers grown from eye
      muscle explants. These cells exhibited a population of high affinity IGF-1
      binding sites (Kd, 0.5nM SEM +/- 0.05). IgG prepared from sera taken from
      patients with Graves' disease (n = 23) significantly inhibited [125I]IGF-1
      binding to orbital fibroblasts when compared to IgGs prepared from normal
      volunteers (n = 13, p < 0.002). It was found that 12 of 23 (52%) patients' IgG
      samples gave rise to significant levels of inhibition of [125I]IGF-1 binding to
      orbital fibroblasts. The IgG preparations did not bind directly to IGF-1. This
      study demonstrates that IgG prepared from patients with Graves' disease with or
      without overt ophthalmopathy interact with IGF-1 binding sites on orbital
      fibroblasts whereas IgG from normal subjects had no significant effect.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7517704
TI  - T cell activation by autoantigens in multiple sclerosis.
AB  - A panel of autoantigens (myosin, actin, myelin basic protein MBP, and
      thyroglobulin) was used to analyze antigen recognition by the peripheral blood
      leukocytes (PBL) of patients with active and stable multiple sclerosis (MS),
      patients with other neurological diseases (OND) and healthy individuals. The
      immune responsiveness was studied by examining the in vitro cell proliferation
      and the increase in the expression of two T-cell-surface activation markers (the
      interleukin-2 receptor IL-2R, and a late activation antigen recognized by the
      19.2 monoclonal antibody). In MS, autoantigen recognition occurred more
      frequently than in the other groups and it was manifested by moderate
      proliferation or marked elevation of the expression of the IL-2R, whereas
      autoantigen recognition in the other groups concerned essentially the expression
      of the late activation antigen. Results similar to those described above were
      obtained with enriched T lymphocytes either in the presence or absence of IL-2.
      Our results suggest that the peripheral immune system in MS patients may
      recognize and can be activated by different autoantigens and not only by MBP, and
      that this response is quantitatively and qualitatively different from that of PBL
      from OND patients and healthy individuals.

PMID- 7517706
TI  - Monoclonal anti-gamma interferon antibodies enhance experimental allergic
      encephalomyelitis.
AB  - Interferon-gamma (IFN-gamma) is a cytokine with multiple activities on a variety
      of cells. Under various circumstances, IFN-gamma can exhibit either pro
      inflammatory or inhibitory actions. Treatment of SJL/J mice with a monoclonal
      antibody (Mab) to IFN-gamma during the afferent limb of the immune response to
      myelin protein produced an enhancement of acute experimental allergic
      encephalomyelitis (EAE), with increased morbidity, mortality and earlier onset of
      disease. Systemic administration of IFN-gamma did not improve or worsen clinical
      outcome, but delayed disease onset. Passive transfer of immune lymph node cells
      co-activated with MBP and anti-IFN-gamma Mab resulted in more sever disease than
      that induced by MBP stimulated cells or MBP and IFN-gamma co-stimulated cells.
      However, in vitro proliferation of an MBP specific T cell line was not influenced
      by IFN-gamma nor anti-IFN-gamma treatment. Mab to IFN-gamma inhibited suppressor
      function, in a non-specific assay. These in vivo and in vitro results suggest
      that systemic IFN-gamma serves as a physiological regulator of a suppressor
      mechanism in EAE. The abrogation of this regulatory mechanism by anti-IFN-gamma
      administration contributes to a more severe form of experimental allergic
      encephalomyelitis.

PMID- 7517707
TI  - Alpha and beta subunits of the gastric H+/K(+)-ATPase are concordantly targeted
      by parietal cell autoantibodies associated with autoimmune gastritis.
AB  - We have previously shown that parietal cell autoantibodies predominantly react
      with a 60-90 kDa gastric autoantigen, subsequently identified as the beta subunit
      of the gastric H+/K(+)-ATPase (EC 3.6.1.3) (proton pump) whereas Karlsson et al
      showed that these autoantibodies primarily target the 95 kDa alpha subunit of the
      pump. In view of these discordant results, we have reassessed the reactivity of
      parietal cell autoantibodies with the two subunits of the gastric H+/K(+)-ATPase.
      We show here that all 26 parietal cell autoantibody-positive sera immunoblot both
      subunits under appropriate, but mutually exclusive, conditions. Thus, reactivity
      of anti-parietal cell autoantibodies with the 95 kDa alpha subunit is optimal
      when the SDS-PAGE is carried out with samples which are reduced but not boiled.
      Whereas reactivity with the 60-90 kDa beta subunit is optimal with samples which
      are boiled but not reduced. Autoantibody reactivity with the beta subunit is
      critically dependent on the presence of a full complement of N-linked glycans
      since partially deglycosylated protein, and recombinant beta subunit expressed in
      COS cells, bearing high mannose N-glycans, failed to bind to the autoantibody.
      These studies also suggest that B cell auto-epitopes are located on the lumenal
      domain of the beta subunit. Reactivity of parietal cell autoantibodies with a
      bacterial fusion protein incorporating the catalytic cytoplasmic domain of the
      alpha subunit suggests the presence of auto-epitopes in this region of the
      molecule.

PMID- 7517708
TI  - Cross-reactivity of an anti-proteinase 3 antibody to elastase.

PMID- 7517709
TI  - Sera from JRA patients contain antibodies against a defined epitope in
      chromosomal protein HMG-17.
AB  - Autoantibodies against the nonhistone nucleosomal protein HMG-17 have been
      detected in a high percentage of ANA-positive patients with pauciarticular-onset
      JRA4. Here we report on the epitope mapping of the HMG-17 autoantigen with a set
      of overlapping and nested synthetic peptides spanning the entire amino acid
      sequence of the human HMG-17 protein. Competition ELISA experiments defined a
      proline and lysine rich octapeptide PKPEPKPK as the major epitope recognized by
      more than 70% of the HMG-17 positive JRA sera. Point mutations introduced in the
      autoimmune peptide determined the amino acid residues important for autoantibody
      recognition. Computer based sequence comparison shows close homology between the
      HMG-17 autoimmune epitope and certain infectious organisms, supporting the
      possibility that molecular mimicry is an important factor in the etiology of JRA.

PMID- 7517711
TI  - In vitro study of olfactory receptor neurones expressing the dipeptide carnosine.
AB  - Olfactory neuroepithelial (OE) cells were dissociated from late stage embryonic
      mice and analysed for carnosine expression. The yield of carnosine neurones was
      twice as high when the OE cells were seeded along with the olfactory bulb cells.
      Carnosine neurones resulted from both in vitro survival and neurogenesis, and
      were associated with clusters of underlying flat cells immunopositive for
      keratin. Our results demonstrate that olfactory neurones expressing their
      neurotransmitter carnosine can be studied in culture, and the close association
      with keratin-immunopositive basal cells suggests that they are dependent on these
      cells for survival and/or differentiation.

PMID- 7517712
TI  - A carboxyl terminal truncation mutant of CD36 is secreted and binds
      thrombospondin: evidence for a single transmembrane domain.
AB  - CD36 has been implicated in several intracellular signalling events, including
      platelet and monocyte activation, and receptor-mediated internalization of bound
      ligands such as oxidized low-density lipoprotein and apoptotic neutrophils. These
      processes are presumably mediated by the intracytoplasmic domain(s) of the
      molecule. By analysis of hydrophobicity plots and by analogy to rat LIMPII, which
      has a 60% homology to CD36, a two-transmembrane domain model has been proposed.
      To characterize the structure-function relationships of CD36 involved in
      transducing the signal, we have defined the number of transmembrane and
      intracellular domains experimentally using a mutagenesis approach. A truncated
      CD36 cDNA was constructed that encodes a protein that terminates just proximal to
      the putative C-terminal transmembrane domain. This mutant was cloned into
      eukaryotic expression plasmid vectors to generate short-term and stable
      transfected cells. Our results indicate that the truncated mutant is secreted by
      the transfectants into the postculture medium, indicating that there is only one
      transmembrane domain in CD36, which is present at the C-terminal end. The soluble
      secreted protein from all of these cells is functional as indicated by its
      binding to thrombospondin.

PMID- 7517713
TI  - Stem cell factor enhances the survival but not the self-renewal of murine
      hematopoietic long-term repopulating cells.
AB  - The effects of stem cell factor (SCF) have been tested on a murine bone marrow
      subpopulation (RH123lo, Lin-, Ly6A/E+) that is highly enriched for long-term
      hematopoietic repopulating cells. SCF maintained cells from this population with
      long-term repopulating ability for up to 10 days in vitro. However, compared with
      freshly isolated cells, the level of engraftment in vivo by the cultured cells
      declined during the in vitro culture period, suggesting that SCF alone was unable
      to stimulate the self-renewal of long-term repopulating cells. By direct
      visualization of cultures, only small numbers of cells survived and rarely
      underwent cell division. However, SCF did directly stimulate proliferation of a
      population (Rh123med/hi,Lin-,Ly6A/E+) enriched for short-term repopulating cells.
      These data suggest that stem cell differentiation is associated with the
      development of mitogenic activity by SCF at least in some progenitor cell
      populations.

PMID- 7517714
TI  - Adhesion of NFS-60 myeloid leukemia cells to MC3T3-G2/PA6 stromal cells induces
      granulocyte colony-stimulating factor production.
AB  - To examine the interaction between immature myeloid cells and stromal cells in
      the induction of granulocyte colony-stimulating factor (G-CSF) production,
      stromal cells of the MC3T3-G2/PA6 (PA6) murine cell line, which has preadipocyte
      characteristics and can support hematopoiesis, were cocultured with various
      myeloid cell lines and G-CSF mRNA expression was examined by Northern and reverse
      transcriptase-polymerase chain reaction analyses. A significant amount of G-CSF
      mRNA was induced by the culture of an interleukin-3/G-CSF-dependent murine
      myeloid leukemia cell line, NFS-60, on PA6 stromal cells for 16 hours. Using a G
      CSF-dependent subline of DA-1 (DA-1N), the biologic activity of G-CSF was also
      detected in PA6/NFS-60 coculture supernatants, but not in the culture supernatant
      of PA6 or NFS-60 alone. Direct contact of NFS-60 cells with the PA6 stromal layer
      was essential for the induction of G-CSF mRNA, as indicated by the following
      observations: (1) NFS-60 cells efficiently adhered to PA6 cells; (2) medium
      conditioned by NFS-60 cells did not contain the activity to induce G-CSF mRNA in
      PA6 cells; and (3) induction of G-CSF mRNA was not observed when NFS-60 cells
      were separated from PA6 cells by a microporous membrane (0.45-microns pore size).
      Several other myeloid cell lines, including FDC-P2, 32Dcl3, WEHI-3, and DA-1, did
      not induce G-CSF mRNA expression after the coculture with PA6 cells, although
      significant numbers of these cells adhered to PA6 cells. Therefore, NFS-60 cells
      may express or overexpress a molecule that is involved in adhesion-mediated
      induction of G-CSF production.

PMID- 7517710
TI  - In vivo cytokine gene expression in various T cell subsets of the autoimmune
      MRL/Mp-lpr/lpr mouse.
AB  - We have used the reverse transcriptase polymerase chain reaction (RT-PCR)
      technique to assess the expression of cytokine genes in various T cell subsets of
      autoimmune-prone mice. Our study confirmed the previously described features in
      lpr mice that IFN-gamma, TNF-alpha, and TNF-beta were transcribed by various T
      cell subsets. We in this study demonstrated that double negative (DN) T cells,
      the major cell population in lpr mice, failed to express interleukin-3 (IL-3), IL
      4, IL-5, and IL-6 genes that influence B cell growth and activation. In contrast,
      DN T cells expressed Eta-1 gene that is shown to augment polyclonal activation of
      B cells and immunoglobulin production. Thus, it is conceivable that T cell
      derived B cell-stimulatory activities in MRL/lpr mice can be attributed to Eta-1,
      rather than IL-3, IL-4, IL-5 or IL-6. We also demonstrated that CD4+ T cells
      infiltrating into kidney tissues of MRL/lpr mice expressed various cytokine genes
      such as IL-1, IL-5, IL-6, IFN-gamma, TNF-alpha, TNF-beta and TGF-beta.

PMID- 7517715
TI  - Human fetal bone marrow early progenitors for T, B, and myeloid cells are found
      exclusively in the population expressing high levels of CD34.
AB  - Experimentation on human stem cells is hampered by the relative paucity of this
      population and by the lack of assays identifying multilineage differentiation,
      particularly along the lymphoid lineages. In our current study, phenotypic
      analysis of low-density fetal bone marrow cells showed two distinct populations
      of CD34+ cells: those expressing a high density of CD34 antigen on their surface
      (CD34hi) and those expressing an intermediate level of CD34 antigen (CD34lo).
      Multiple tissues were used to characterize the in vitro and in vivo potential of
      these subsets and showed that only CD34hi cells support long-term B lymphopoiesis
      and myelopoiesis in vitro and mediate T, B, and myeloid repopulation of human
      tissues implanted into SCID mice. CD34lo cells repeatedly failed to provide long
      term hematopoietic activity in vivo or in vitro. These results indicate that a
      simple fractionation based on well-defined CD34 antigen levels can be used to
      reproducibly isolate cells highly enriched for in vivo long-term repopulating
      activity and for multipotent progenitors, including T- and B-cell precursors.
      Additionally, given the limited variability in the results and the high
      correlation between in vitro and in vivo hematopoietic potential, we propose that
      the CD34hi population contains virtually all of the stem cell activity in fetal
      bone marrow and therefore is the population of choice for future studies in
      hematopoietic stem cell development and gene therapy.

PMID- 7517718
TI  - Fc-independent cross-linking of a novel platelet membrane protein by a monoclonal
      antibody causes platelet activation.
AB  - A monoclonal antiplatelet antibody (MA-13G8E1) is described that dose-dependently
      induces platelet aggregation and serotonin release in an Fc-independent fashion.
      Whereas platelets were equally aggregated by F(ab')2 fragments of this monoclonal
      antibody (MoAb), its Fab fragments, on the other hand, were inactive, indicating
      that divalent interaction is an essential requirement to induce platelet
      activation by MA-13G8E1. In addition, we could show that platelet epitope cross
      linking by MA-13G8E1 occurred on the same platelet. MA-13G8E1 stimulated platelet
      phospholipase C (PLC) and induced activation of protein kinase C (PKC), both of
      which were almost unaffected by aspirin pretreatment. Furthermore, PLC activation
      appeared to be a direct antibody-mediated effect, since intracellular Ca2+ rises
      were not inhibited by EGTA, cytochalasin B, or aggregation-blocking MA-16N7C2
      (antiglycoprotein [anti-GP]IIb/IIa). The MA-13G8E1 antigen is constitutively
      expressed on resting platelets of different species (7,100 +/- 800 molecules per
      human platelet), but not on other cell types tested. Both immunoprecipitation and
      affinity isolation by MA-13G8E1 showed two low-molecular weight proteins (45 and
      36 kD), having slightly acidic isoelectric pH levels (4.5 to 5.5) and forming
      multimolecular complexes. In conclusion, we found an MoAb that is able to induce
      platelet activation in an Fc-independent fashion. The mechanism involves cross
      linking of a hitherto undescribed platelet membrane protein, leading to PLC and
      PKC stimulation.

PMID- 7517717
TI  - The development of assays for the detection of fibrin(ogen)olysis based on COOH
      terminal A alpha chain epitopes.
AB  - The COOH-terminal two-thirds of the fibrinogen A alpha chain is a substrate for
      both factor XIIIa and plasmin and is, therefore, a source of structural markers
      for the clinical detection of fibrin(ogen)olysis. Monoclonal antibodies (MoAbs)
      that bind to epitopes within this region (F-102, A alpha 563-578; F-103, A alpha
      259-276) have been applied towards the development of two sensitive and specific
      enzyme-linked immunosorbent assays (ELISAs). The first assay, a capture (F-102)
      tag (F-103) ELISA, measures plasma fibrinogen molecules whose A alpha chains are
      intact. The second assay, a solution phase competitive ELISA based on MoAb F-102,
      quantifies circulating COOH-terminal A alpha chain degradation products (A alpha
      FDPs), among the earliest peptides released from fibrinogen during plasmin
      mediated fragment X formation. This assay features a novel preliminary plasma
      absorption step on concanavalin A to recover A alpha FDPs (if present in the
      sample) in a milieu free of immunologically cross-reactive fibrinogen. Both
      ELISAs use highly purified fibrinogen as the assay standard for quantitation. In
      control plasmas, circulating A alpha FDPs accounted for less than 2% of their
      respective intact fibrinogen A alpha chain concentration, suggesting a
      physiologic low level of proteolysis occurring at the extreme COOH-terminal
      portion of the molecule. Plasma A alpha FDPs were elevated (2.3% to 7.8% of their
      respective intact fibrinogen A alpha chain concentration) in a group of plasma
      from patients with documented, high serum FDPs (21 to 41 micrograms/mL).
      Application of the two ELISAs to characterize the course of A alpha chain
      proteolysis during thrombolytic therapy (TIMI phase 1) indicated that A alpha
      FDPs were a very early marker of the lytic state (detectable 15 minutes after
      treatment had been initiated), and that streptokinase and recombinant tissue
      plasminogen activator appeared to produce significantly different A alpha chain
      degradation profiles.

PMID- 7517716
TI  - A functionally active retrovirus vector for gene therapy in Fanconi anemia group
      C.
AB  - Fanconi anemia (FA) is a rare genetic disorder characterized by progressive
      pancytopenia, congenital abnormalities, and a predisposition to malignancy.
      Recently, mutation in a novel gene named FACC (Fanconi anemia C complementing)
      has been identified as causing one type of FA. Here, we report successful
      functional complementation of four FA(C) cell lines using a retroviral vector to
      transfer a copy of the normal FACC gene. The hallmark of the FA cell phenotype is
      extreme sensitivity to cross-linking agents such as mitomycin C (MMC). Cell lines
      transduced by FACC viral vectors were distinguished by their ability to grow at
      concentrations of MMC several orders of magnitude higher than those
      concentrations inhibitory of parental controls. The genetically corrected cell
      lines were analyzed for susceptibility to MMC-induced chromosomal breakage and
      were found to have been normalized. These two different assays confirmed that our
      retroviral vectors were capable of transferring a functional FACC gene to
      lymphoid cell lines established from FA(C) patients. We next analyzed the ability
      of our viral vectors to functionally correct hematopoietic progenitor cells from
      a patient bearing a splice donor mutation. Progenitor cells were purified by an
      immunoaffinity column to enrich for cells with high CD34 expression. Similar to
      FA lymphoid cell lines, this patient's CD34-enriched cells were extremely
      sensitive to MMC. After infection of these progenitor cells with viral vectors
      bearing normal FACC, increased numbers of colonies formed both in the absence and
      presence of < or = 5 nmol/L MMC, but no colonies formed from uninfected cells,
      even in the absence of MMC. Polymerase chain amplification was used to confirm
      proviral DNA integration. Thus, retroviral vectors can be engineered to transfer
      a normal FACC gene to lymphoid cell lines and primary hematopoietic cells bearing
      four different FACC mutations. FA stem cells rescued by gene transduction should
      have a selective growth advantage within the hypoplastic FA marrow environment in
      vivo. These experiments suggest that gene therapy may be an effective treatment
      strategy for FA.

PMID- 7517719
TI  - Killing of autologous B-lineage malignancy using CD3 x CD19 bispecific monoclonal
      antibody in end stage leukemia and lymphoma.
AB  - To develop an effective tumor immunotherapy for B-lineage non-Hodgkin's lymphoma
      (NHL) and acute lymphoblastic leukemia (ALL), a bispecific monoclonal antibody
      (BsAb) has been generated with the first specificity for the CD3 epsilon-chain
      and the second for the CD19 antigen. Peripheral blood mononuclear cells (PBMCs)
      isolated from patients with NHL or ALL during remission or relapse rapidly
      proliferated (up to 179-fold increase) on in vitro activation combining
      phytohemagglutinin or CD3 monoclonal antibody with interleukin-2. After 3 weeks
      of stimulation, more than 90% of the PBMCs was CD3+ and CD8+, even when cultures
      were started with only 5% CD3+ cells. Cytotoxic activity against autologous
      malignant B cells was markedly enhanced (from 5% baseline to 70% lysis) by the
      addition of the CD3 x CD19 BsAb in all samples tested. Immunophenotypic
      examination of a series of tumor target cells showed that all samples examined
      showed CD54 (intercellular adhesion molecule-1) and HLA class I, but showed no B7
      expression. CD11a (lymphocyte function-associated antigen-1) expression was
      heterogeneous. Various types of experiments showed that efficient CD3 x CD19 BsAb
      mediated cytolytic capacity was not dependent on expression of either of these
      surface proteins. This contrasts with normal major histocompatibility complex
      restricted antigen-specific cytotoxicity and may be essential for effective in
      vivo application of this BsAb.

PMID- 7517720
TI  - Differences in constitutive and post-methotrexate folylpolyglutamate synthetase
      activity in B-lineage and T-lineage leukemia.
AB  - Folylpolyglutamate synthetase (FPGS) is responsible for the metabolism of natural
      folates and a broad range of folate antagonists to polyglutamate derivatives.
      Recent studies indicated increased accumulation of methotrexate (MTX)
      polyglutamates (MTX-PG) in blast cells as a predictor of favorable treatment
      outcome in childhood acute lymphoblastic leukemia (ALL). We determined the
      expression of FPGS activity in blasts from children with ALL at diagnosis and
      after treatment with MTX as a single agent, before conventional remission
      induction therapy. The levels of enzyme activity in ALL blasts at diagnosis
      (median of 689 pmol/h/mg protein) were significantly higher (P = .003) than those
      found in acute nonlymphoblastic leukemia (ANLL) blasts (median of 181 pmol/h/mg
      protein). Comparable lineage differences in normal lymphoid versus nonlymphoid
      cells suggest a lineage-specific control of FPGS expression, FPGS activity
      increased in ALL blasts after in vivo exposure to MTX. The median increase in
      FPGS activity was significantly higher (P = .003) in B-lineage ALL (188%) than in
      T-lineage ALL (37%). Likewise, the percentage of intracellular long chain MTX-PG
      (Glu3-6) was significantly higher (P = .02) in B-lineage ALL (92%) than in T
      lineage ALL (65%), consistent with higher FPGS activity in B-lineage blasts. This
      finding could explain, at least in part, the superior outcome in children with B
      lineage ALL treated with antimetabolite therapy.

PMID- 7517721
TI  - Evidence for nonclonal hematopoietic progenitor cell populations in bone marrow
      of patients with myelodysplastic syndromes.
AB  - Clonality of marrow hematopoietic progenitor cells in myelodysplastic syndromes
      (MDS) was analyzed by X-chromosome inactivation pattern using polymerase chain
      reaction (PCR). Five female patients were included in this study; two with
      refractory anemia (RA) and three with RA with excess blasts (RAEB). They were
      heterozygous for BstXI restriction fragment length polymorphisms (RFLP) of the X
      chromosome-linked phosphoglycerate kinase (PGK) gene. In each patient, erythroid
      and nonerythroid colonies, grown in the presence of erythropoietin and
      granulocyte-macrophage colony-stimulating factor (GM-CSF), exhibited no
      remarkable difference in clonal constitution. Two patients showed only one
      methylation pattern, suggesting the monoclonal origin of hematopoietic progenitor
      cells. Colonies of two other patients exhibited predominant and minor methylation
      patterns in PGK gene, indicating that nonclonal progenitor cells remain a minor
      population. The bone marrow of one patient appeared to contain a greater
      proportion of nonclonal progenitors. Stem cell factor (SCF), a potent colony
      stimulating factor, enhanced both erythroid and nonerythroid colony formation.
      However, it did not notably alter the clonal constitutions. We conclude that
      nonclonal hematopoietic progenitor cells can persist in a substantial number of
      MDS patients.

PMID- 7517722
TI  - Antibodies to myeloid precursor cells in autoimmune neutropenia.
AB  - Antibodies to mature blood neutrophils and to bone marrow myeloid cells have been
      described in the sera of some patients with apparent autoimmune neutropenia. To
      further explore the prevalence and specificities of antibodies to myeloid
      precursor cells, we evaluated sera from 148 patients with suspected autoimmune
      neutropenia for the presence of antibodies to neutrophils, to cultured myeloid
      cell lines, and to highly purified bone marrow myeloid progenitor cells. Using an
      immunofluorescence flow cytometric assay, we identified IgG antibodies in 42
      (28%) of these sera that bound specifically to K562 cells, a multilineage cell
      line originally derived from a patient with chronic myelogenous leukemia. Twenty
      two (15%) of the sera also contained IgG antibodies that bound specifically to
      the primitive myelomonocytic leukemia cell line KG1a. Twenty-five (17%) of the
      sera had IgG antibodies to myeloid cell lines in the absence of antibodies to
      mature neutrophils. There was a trend toward more severe neutropenia in patients
      with antibodies to K562 cells, without antineutrophil antibodies. In further
      studies, antibodies from 12 sera bound to mononuclear CD34+ cells that had been
      purified from normal human bone marrow by an immunomagnetic separation procedure.
      Moreover, two of these sera suppressed the growth of granulocyte-macrophage
      colony-forming units (CFU-GM) in methylcellulose cultures. The presence of
      antibodies to primitive hematopoietic cells in the sera of some patients with
      suspected immune neutropenia suggests that these antibodies may have a role in
      the pathogenesis of the neutropenia observed.

PMID- 7517723
TI  - The acute chest syndrome in sickle cell disease: incidence and risk factors. The
      Cooperative Study of Sickle Cell Disease.
AB  - The acute chest syndrome (ACS), a pneumonia-like illness in sickle cell patients,
      is one of the most frequent causes of their morbidity and hospitalizations.
      Repeated ACS events may predict the development of chronic lung disease. ACS is
      reported as a frequent cause of death in these patients. We examine here the
      incidence and risk factors of ACS in 3,751 patients with sickle cell disease who
      were observed prospectively for at least 2 years (19,867 patient-years [pt-yrs])
      as part of a multicenter national study group. The ACS, defined by a new
      pulmonary infiltrate on x-ray, occurred at least once in 1,085 patients (2,100
      events). ACS incidence was higher in patients with homozygous sickle cell disease
      (SS; 12.8/100 pt-yrs) and in patients with sickle cell-beta(0) -thalassemic
      (9.4/100 pt-yrs), and lower in patients with hemoglobin (Hb) SC disease (5.2/100
      pt-yrs) and patients with sickle cell-beta(+) thalassemia (3.9/100 pt-yrs). alpha
      Thalassemia did not affect the rate of ACS incidence in SS patients. Within each
      Hb type the incidence was strongly but inversely related to age, being highest in
      children 2 to 4 years of age (25.3/100 pt-yrs in SS) and decreasing gradually to
      its lowest value in adults (8.8/100 pt-yrs in SS). In SS children (< 10 years of
      age), we documented an age-related within-person reduction in ACS attack rates.
      Adults with a higher ACS rate had a higher rate of mortality (from all causes)
      than those with low ACS rates. This increased rate of mortality might also have
      contributed to the decline in ACS rate with age. In multivariate analysis, other
      factors affecting incidence in SS patients were degree of anemia (lower ACS rates
      in patients with lower steady-state Hb levels) and fetal Hb (lower rates in
      patients with high fetal Hb). There was also a positive association between ACS
      rate and steady-state leukocyte count. The relationship of ACS rate to higher
      steady-state Hb levels in SS patients is unexplained but might be caused by
      increased blood viscosity.

PMID- 7517724
TI  - Erythrocyte membrane proteins reactive with IgG (warm-reacting) anti-red blood
      cell autoantibodies: II. Antibodies coprecipitating band 3 and glycophorin A.
AB  - In our initial immunochemical study of the red blood cell (RBC) membrane proteins
      targeted in 20 cases of warm-antibody autoimmune hemolytic anemia (AHA), RBC
      eluates of 6 patients mediated immunoprecipitation (IP) of both band 3 and
      glycophorin A (GPA). This dual IP pattern had previously been observed with
      murine monoclonal antibodies (MoAbs) against the high frequency blood group
      antigen, Wrb (Wright), suggesting that the Wrb epitope may depend on a band 3-GPA
      interaction. Earlier, anti-Wrb had been identified serologically as a prominent
      non-Rh specificity of AHA autoantibodies. In the present study, 6 autoantibody
      eluates immunoprecipitating band 3 and GPA from common Wr(b+) RBCs were retested,
      in parallel with murine anti-Wrb MoAbs, against very rare Wr(a+b-)En(a+)RBCs. One
      patient's autoantibodies were unreactive with the Wr(b-) RBCs by either IP or
      indirect antiglobulin test (IAT) and were judged to have "pure" anti-Wrb
      specificity. Two other patients' autoantibodies displayed both IP and serologic
      evidence for anti-Wrb as a major component in combination with one or more
      additional specificities. However, among 3 other patients whose autoantibodies
      coprecipitated band 3 and GPA, there was no reduction in IP or IAT reactivity
      with Wr(b-) RBCs in 2 and only slight reduction in the third. We conclude (1)
      that human anti-Wrb autoantibodies, like their murine monoclonal counterparts,
      coprecipitate band 3 and GPA from human RBCs; but (2) that not all antibodies
      with this IP behavior have anti-Wrb serologic specificity, as defined by this
      donor's Wr(b-) RBCs. The possibility of an additional (non-Wrb) RBC epitope
      dependent on a band 3-GPA interaction is raised.

PMID- 7517727
TI  - Light microscopic visualization of diamine oxidase using a cerium method.
AB  - Diamine oxidase (DAOX) can be localized in the light microscope using
      immunohistochemistry, but a reliable procedure for detecting the activity of the
      enzyme does not exist. A method was thus developed in which cerium ions trap
      H2O2, generated by DAOX, and a diaminobenzidine-H2O2-Co sequence serves for the
      visualization of the primary reaction product cerium perhydroxide. With this
      method and diamine substrates cadaverine or putrescine, or polyamine substrates
      spermidine or spermine as substrates, DAOX was localized species-independently
      but substrate-dependently in the basolateral cytoplasm and/or plasma membrane of
      small intestinal enterocytes of rats, mice and gerbils. Less, or even no, final
      reaction product was seen in these cells of guinea-pigs and marmosets. Colonic
      enterocytes were positive for DAOX solely in gerbils. Furthermore, species
      dependent diamine oxidase was present in special cells of the mouse and guinea
      pig kidney, immune organs and liver of rats and gerbils, marmoset placenta and in
      decidual cells of the human, rat and mouse placenta.

PMID- 7517725
TI  - Hepatitis C virus antibody seroconversion in bone marrow transplant recipients
      treated with immune globulin: the impact of the problem.

PMID- 7517726
TI  - Ion fragmentation activated by matrix-assisted laser desorption/ionization in an
      ion-trap/reflectron time-of-flight device.
AB  - An ion-trap storage/reflectron time-of-flight mass spectrometer has been used to
      study the decay of large ions following activation by matrix-assisted laser
      desorption/ionization (MALDI). It is shown that large ions may undergo
      fragmentation over long periods of time, extending even to milliseconds in some
      cases. These fragments are stored in the trap and detected as stable ions in the
      reflectron device, rather than as metastable ions due to decay during the flight
      time to the detector. The ion decay is found to depend strongly on the laser
      intensity, while a smaller effect may be due to the matrix used in the MALDI
      process. The fragmentation observed was found to also depend strongly on the RF
      voltage applied to the ring electrode; higher RF voltage produced enhanced
      fragmentation. A gated RF experiment further demonstrated the importance of the
      level of the RF voltage, during the initial activation event, in producing
      fragmentation. A study of the effects of buffer gas composition and pressure
      showed that increased pressure may result in reduced fragmentation due to
      collisional cooling in the trap. However, the use of argon or nitrogen buffer gas
      at increased pressure in the trap may result in fragmentation upon extraction
      from the trap, producing metastable ions in the flight tube. The implications of
      the use of the time variable for obtaining fragmentation in the trap for rapid
      sequencing are discussed.

PMID- 7517728
TI  - Metachromatic dye-Ca++ATPase method in pathological muscle: a study of 382 muscle
      biopsies.
AB  - The metachromatic dye-Ca++ATPase method, that in normal muscle distinguishes
      fiber types on the basis of their metachromatic or orthochromatic staining, was
      applied to 382 pathological muscle biopsies. Results were compared in serial
      sections with those obtained with the conventional ammonium sulphide method. In
      pathological muscle the metachromatic dye-Ca++ATPase method confirms the
      advantages already showed in normal muscle: fast and easy performance, neat fiber
      typing, simultaneous staining of nuclei. Moreover in pathological muscle the
      metachromatic dye-Ca++ATPase method showed some muscle changes which are missed
      by the conventional ammonium sulphide one, namely central nuclei, macrophagic
      invasion and some structural abnormalities. This allows immediate correlation
      between those alterations and fiber typing.

PMID- 7517734
TI  - Sex, hormones, and the developing neuron.

PMID- 7517732
TI  - On the structural differences in the membranes between ciliated bronchial and non
      ciliated lymphoepithelium in rats.
AB  - The membrane structure of bronchial ciliated epithelium and lymphoepithelium was
      studied in rats by lectin histochemistry. The lymphoepithelium, contrary to
      bronchial ciliated epithelium, did not contain terminal beta-D-galactose
      residues. Moreover L-fucose and beta-D-Gal (1-3)-D-GalNAc residues, being masked,
      could be visualized only after enzymatic digestion of terminal sialic acid. These
      structural differences in membranes provide a basis for the different functions
      of bronchial lymphoepithelium.

PMID- 7517731
TI  - Recurrent chromosome alterations in non-small cell lung cancer.
AB  - Cytogenetic analysis of 28 cases of non-small cell lung cancer (NSCLC) was
      carried out in an attempt to determine karyotype changes involved in the early
      state of disease. Our findings indicate that, even though karyotypes are very
      complex, recurrent cytogenetic changes can be identified. The most common
      structural rearrangements were deletions of chromosomes 3, 17 and 9. The most
      frequent numerical alterations were gain of chromosomes 7 and 20 and loss of
      chromosomes 1 and Y. In particular, the high frequency of deletions suggests a
      critical role of suppressor oncogenes in these chromosome regions in tumor
      development.

PMID- 7517729
TI  - A new fluorescence reaction in protein cytochemistry: formation of naphthalimide
      fluorophores from primary amino groups and 1,8-naphthalic anhydride derivatives.
AB  - In this work we describe the formation of fluorescent naphthalimide derivatives
      as a new cytochemical method for revealing protein amino groups. The reaction is
      based on the condensation of 1,8-naphthalic anhydrides in organic solvents with
      primary aliphatic amines. Under optimal violet-blue (436 nm) excitation, a strong
      yellow-green emission is observed in specific cell components from blood smears
      treated with 3-amino-1,8-naphthalic anhydride in N,N-dimethylformamide, which
      were the most suitable reagent and solvent for microscopic studies. Cytoplasmic
      granules of mammalian eosinophils and avian heterophils showed the highest
      fluorescence reaction, which was abolished by blocking procedures for amino
      groups. Spectrofluorometric analysis confirmed the emission characteristics of
      the naphthalimides produced from n-butylamine and gelatin. Taking into account
      the chemical reactivity of 1,8-naphthalic anhydrides and present results, the
      reaction can be considered selective for lysine and arginine residues of
      proteins.

PMID- 7517730
TI  - Influence of ammonia solution on gastric mucosa and acetic acid induced ulcer in
      rats.
AB  - Aqueous ammonia in concentrations of 0.02 or 0.1% was continuously administered
      to rats to study its effect on the gastric mucosa histologically and cell
      kinetically. Furthermore, acetic acid ulcer, which is a model of chronic gastric
      ulcer, was experimentally induced in the stomachs of rats to assess the influence
      of 0.02% ammonia on the course of this ulcer. Male Donryu rats were divided into
      three groups given 0.02% ammonia, 0.1% ammonia or tap water. On several occasions
      (1, 3 and 5 days and 1, 4, 8, 12 and 24 weeks from the beginning of the
      experiment), the gastric mucosa in the fundic gland region and the antrum was
      examined histologically, and from the viewpoint of cell kinetics. The assessment
      in the 8th and 24th weeks employed the double labeling technique with
      bromodeoxyuridine and 3H-thymidine. The assessment on the other occasions used
      the flash labeling technique with bromodeoxyuridine. Both the 0.02% and 0.1%
      ammonia treatment groups showed a decrease in PAS-positive mucus and an enhanced
      cell cycling in the early stage of the experiment. After long periods of
      treatment, these groups showed a reduction in the gland height, a recovery in PAS
      positive mucus and a suppression of cell cycle, suggesting direct toxicity of
      ammonia on the gastric mucosa. Although glandular atrophy was observed in these
      animals, infiltration of inflammatory cells was not observed. Thus, the
      relationship between ammonia and gastritis remained obscure. No ulcer developed
      in any group. Subsequently, we experimentally induced Ul-IV or Ul-V acetic acid
      ulcers in the stomachs of rats, according to the method of Okabe et al. (1971,
      1972). These rats were divided into two groups given 0.02% ammonia or tap water.
      In the 4th and 8th weeks of the experiment, the stomachs of these rats were
      examined histologically and from the viewpoint of cell kinetics. The 0.02%
      ammonia treatment group showed a significant increase in the ulcer index (long
      diameter x short diameter; mm2) in the 4th and 8th weeks. This group also showed
      suppressed cell cycling of the regenerative epithelium and fibroblasts in the
      ulcer margin, suggesting direct toxicity of ammonia. Thus, healing of peptic
      ulcer was delayed by continuous administration of 0.02% ammonia.

PMID- 7517733
TI  - Neurotensin immunoreactive cells in the gastrointestinal epithelium of the
      chicken, pigeon and Japanese quail.
AB  - Distribution and frequency of neurotensin immunoreactive cells were investigated
      in the digestive tract of the chicken, pigeon and Japanese quail by an
      immunohistochemical technique. Immunoreactive cells were distributed in the
      epithelium of the pylorus, duodenum, jejunum, ileum, caecum and colon, but not in
      the epithelium of the tongue, crop and esophagus. The pylorus showed the highest
      frequency of the immunoreactive cells in the three species and the chicken
      revealed the highest frequency among them. In the chicken and Japanese quail,
      there were a few immunoreactive cells in the epithelium of the proventriculus and
      gizzard. In the caecum, the pigeon showed the highest frequency in the three
      species, although the size of the caecum is very small. These results indicate
      that neurotensin cells in the avian digestive tract show similar patterns of
      localization and suggest that the avian gastrointestinal tract acts as a wide
      source of neurotensin secretion.

PMID- 7517736
TI  - Endothelial cell proteases: physiological role and regulation.
AB  - Endothelial cell-derived proteases can be classified according to their
      physiological role. The proteases involved in extracellular matrix degradation
      are important in endothelial cell migration and thereby in angiogenesis. They
      include the urokinase-type plasminogen activator (uPA) and the metalloproteases,
      collagenases, gelatinases and stromelysin. uPA secreted from endothelial cells
      remains associated with the cell membrane, on specific receptors localized in the
      vicinity of the receptors for plasminogen. This favours the local activation of
      plasminogen into plasmin. Plasmin, generated on the cell surface, is fully active
      as it is not inhibited by alpha 2-antiplasmin. Plasmin acts directly by degrading
      some components of the extracellular matrix and indirectly by activating the
      prometalloproteases. Secretion of PAI by migrating cells is generally stimulated
      by the same factors that induce uPA secretion, limiting the degradation of the
      matrix to the pericellular path. The degradation of the fibrin clot involves the
      tissue-type plasminogen activator tPA, which like the uPA activates plasminogen
      to plasmin. This system is also regulated by two different mechanisms. On the one
      hand, fibrin itself favours its own degradation by formation of a ternary
      complex, fibrin-plasminogen-tPA, in which the affinity of tPA for plasminogen is
      markedly increased, as compared to the affinity of unbound tPA. In addition,
      plasmin generated on the clot is protected from inhibition by alpha 2
      antiplasmin. On the other hand, as for uPA, tPA is inhibited by PAI-1. The
      importance of the regulation of this system is illustrated by the thrombotic risk
      observed when there is either a decrease in tPA or an increase in PAI-1, and
      inversely by haemorrhages in the case of increase in tPA.

PMID- 7517737
TI  - Transcellular biosynthesis of arachidonic acid metabolites: from in vitro
      investigations to in vivo reality.
AB  - The discovery that arachidonic acid metabolism in a multicellular environment
      could be different from that expected from the sum of individual cell types has
      led to the concept of transcellular metabolism. In this process, several cells
      can contribute to the formation of a novel compound with potent biological
      action. The study of this mode of synthesis is important in the context of the
      current appraisal of thrombotic diseases as part of an inflammatory reaction. In
      this context, blood cell-vessel wall interactions present a regulated expression
      of adhesive molecules on either type of cell. These complex processes are
      initiated by signalling molecules such as cytokines that can deeply modify the
      phenotype of endothelial cells, which may ultimately lead to a change in the
      vascular tone and to atherosclerotic complications. Such reaction processes are
      part of the autocrine-endocrine system whereby cells can control and modify their
      own phenotype through the action of a local network of mediators. In this
      context, arachidonic acid metabolites may be an important part of unifying signal
      molecules that participate in these changes. The significance of transcellular
      biosynthesis where combined cells acquire a different metabolic potential can be
      viewed as an additional modification of blood cell and vessel cell phenotype in
      thrombotic diseases.

PMID- 7517735
TI  - Histochemical reactions of the secretory cells of the Stannius corpuscles in
      Palamys sarda L.
AB  - Two cell types have been identified in the Stannius corpuscles of Palamys sarda
      L. They are distinguished by the presence or absence of granules. Histochemical
      studies have shown that the granules contain proteins with - NH2 radicals,
      glycoproteins, sulfomucins, carboxymucins and cholesterol. The two cell types
      might represent different stages of a single functional cell type.

PMID- 7517738
TI  - Tumour angiogenesis.
AB  - The progressive emergence of a close relationship between the formation of blood
      vessels in the vicinity of tumour cells and the development and spreading of
      tumours, strongly suggests that angiogenesis might be a prerequisite for tumour
      development. Angiogenesis starts and develops in response to two sets of
      extracellular signals: soluble angiogenic factors and extracellular matrix.
      Different experimental models have been used to study angiogenesis in vivo, but
      they have numerous limitations. Three-dimensional culture systems reconstitute
      normal interactions between endothelial cells and the surrounding extracellular
      matrix. Numerous parameters including angiogenic growth factors and cytokines,
      cell-to-cell interactions and cell-to-extracellular matrix adhesion influence the
      growth and differentiation of endothelial cells in vitro as well as in vivo.
      Angiogenesis plays a major role not only in tumour growth but also in metastasis
      development. Mechanisms of switching to angiogenic phenotype have been recently
      described and onset of angiogenic activity is now recognized as another discrete
      step in tumorigenesis. Tumour cells can induce b-FGF expression and exportation,
      VEGF and VEGF receptor expression and inactivation of the cancer suppressor gene
      encoding for a fragment of thrombospondin. A controlled net proteolytic balance
      produced by tumour cells or endothelial cells is required to favour migration and
      invasion of endothelial cells and angiogenesis. The hypothesis that assessment of
      tumour angiogenesis might predict tumour aggressiveness in human cancer has
      recently gained support from several clinical studies. This has been shown for
      cutaneous melanoma, breast carcinoma, and non-small-cell lung cancer by
      quantitation of microvessels in human biopsies using von Willebrand factor or CD3
      antigen labelling with specific antibodies. However, more specific and sensitive
      markers are needed to improve this approach for predicting tumour aggressiveness.
      Folkman proposed twenty years ago that inhibition of angiogenesis might represent
      a suitable complementary strategy for the treatment of various forms of cancer.
      Since then numerous angiostatic compounds have been identified but very few of
      them fit the required criteria of a potential drug. Fumagillin and particularly
      its synthetic analogue AGM 1470 might be developed for use in humans in the near
      future.

PMID- 7517741
TI  - Hepatitis C virus infection. Treatment with interferon reduces viraemia.

PMID- 7517739
TI  - Using outcomes research in clinical practice.

PMID- 7517740
TI  - Hepatitis C virus infection. Define seropositivity.

PMID- 7517742
TI  - A cooperative study on ProMACE-CytaBOM in aggressive non-Hodgkin's lymphomas.
AB  - Chemotherapy using cyclophosphamide, doxorubicin, etoposide, cytarabine,
      bleomycin, vincristine, methotrexate with leucovorin, and prednisone (ProMACE
      CytaBOM) for patients with intermediate or high grade non-Hodgkin lymphomas (G, H
      and K according to the Working Formulation), was tested by the Gruppo Cooperativo
      Lombardo to confirm the activity of the regimen and to test the feasibility and
      safety of administering third-generation drug regimen in a cooperative group
      setting. Among 64 previously untreated patients, aged between 20 and 71 years, 7
      had stage IB-IIB, 12 had stage IIIA-B, 45 (67%) had stage IVA-B. There were 44
      complete remissions (CRs) (69%) and 14 partial remissions (22%); the difference
      between patients in stage I-II-III (84% complete remissions) and those in stage
      IV (62% complete remissions) was statistically significant. The median length of
      follow up was 20 months (range 1-60 months), with 56% of patients alive at 60
      months and 53% of CRs patients free of disease at 60 months. Patients in stage I
      II-III have the best survival and disease free survival compared to stage IV, 87%
      versus 42% and 72% versus 32% respectively (both with high statistical
      significance). Grade 3-4 (WHO) haematological toxicity was observed in 39% of
      patients, with 3 septic deaths. Two more patients died with chemotherapy related
      toxicity (1 stroke and 1 acute renal insufficiency). Administration of ProMACE
      CytaBOM is a feasible and safe regimen although it presents moderate toxicity.
      ProMACE-CytaBOM may represent improved treatment for aggressive lymphomas, in
      terms of duration of response and survival, but a longer follow up is needed.

PMID- 7517744
TI  - The response of diffuse large cell and other intermediate grade non-Hodgkin's
      lymphomas to adriamycin containing combination chemotherapy.
AB  - Adriamycin containing combination chemotherapy (ACCC) is usually delivered to
      patients with stages III, IV diffuse large cell (DLCL) non-Hodgkin's lymphoma
      (NHL). Although this mode of therapy is also commonly used in other intermediate
      grade lymphomas, it's role in the latter subset of patients is not well defined.
      In a retrospective analysis we evaluated and compared the outcome of previously
      untreated DLCL and non-DLCL intermediate grade lymphoma patients who received as
      initial therapy, "first generation" ACCC. No differences in response and relapse
      rates between these subgroups were observed. The trend towards the survival
      advantage observed for the non-DLCL patients, is probably due to a lower
      mortality over 5-8 years, for complete responders.

PMID- 7517745
TI  - The leukemic myeloid cell line OMA-AML-1: an in vitro model of hematopoietic cell
      differentiation.
AB  - The OMA-AML-1, acute myelogenous leukemia cell line is unique in that it
      spontaneously maintains both a CD34+ precursor cell compartment and a CD15+
      differentiating cell compartment in vitro. A third transitional cell type with co
      expression of CD34 and CD15 can also be identified in in vitro cultures. The cell
      line shows dynamic fluctuations in the relative sizes of these three cell
      compartments in suspension culture. In contrast, OMA-AML-1 fails to show
      phenotypic or morphologic evidence of differentiation when grown subcutaneously
      in immunodeficient mice. OMA-AML-1 responds to a number of hematopoietic
      cytokines. Delineation of cytokine responses on FACS isolated populations of
      CD34+ versus CD15+ cells demonstrated that proliferative responses occurred
      primarily at the level of the precursor cell (CD34+) while the production of
      endstage eosinophils occurred within the CD15+ compartment. OMA-AML-1 mimics a
      number of features of normal hematopoiesis and is proving to be a useful in vitro
      model for the study of hematopoietic differentiation.

PMID- 7517746
TI  - The study of acute leukemia cells by means of acridine orange staining and flow
      cytometry.
AB  - The studies described here explored the staining of acute leukemia cells with
      acridine orange (AO). The red fluorescence curve of AML specimens was usually
      bimodal, suggesting the presence of subpopulations of cells which have different
      RNA contents. In almost every AML specimen, small leukemic blast cells comprised
      at least part of the "low RNA content" subpopulation. Residual granulocytes and
      lymphocytes also contributed to this population. Frequently, the green
      fluorescence, indicative of the binding of AO to DNA, was slightly less in these
      cells than in the majority of cells present. There was no evidence however, that
      the leukemia cells with these characteristics represented a G0 or kinetically
      quiescent population of cells. In ALL specimens, the presence of multiple
      cytogenetically distinct clones was easily detectable in AO stained specimens.
      The red fluorescence curve of G0/G1 ALL cells was unimodal.

PMID- 7517747
TI  - CD23 antigen density is related to serum gamma globulin level, bone marrow
      reticulin pattern, and treatment in B chronic lymphocytic leukemia.
AB  - The CD23 antigen density was evaluated by a cytofluorometric technique in 55
      patients with chronic lymphocytic leukemia. The quantification method was based
      on the use of biological standards in indirect immunofluorescence. The CD23
      antigen density was correlated with the percentage of CD23 positive cells, but
      antigen density appeared to be a more informative parameter. CD23 antigen density
      was lower in stage B than in stages A or C patients, and higher in patients
      undergoing chemotherapy or previously treated than in untreated patients. There
      was a significant negative correlation between CD23 antigen density and serum
      gamma globulin and IgG levels, that existed only in patients in an advanced stage
      of the disease. CD23 antigen density was higher in patients with abnormal bone
      marrow reticulin pattern. Serum gamma globulin level was lower in these patients,
      as well as in patients with prognostically unfavorable histologic bone marrow
      infiltration pattern. These data emphasize the interest of antigen density as an
      additional parameter and the complex relationship between CD23 expression,
      hypogammaglobulinemia, bone marrow histologic findings, and treatment in chronic
      lymphocytic leukemia.

PMID- 7517743
TI  - Evidence against the role of hepatitis C virus in severe liver damage occurring
      early in the course of acute leukemia in children.
AB  - Severe liver damage revealed by a sharp transaminase elevation may be seen in
      patients with leukemia. This may be due to several possible causes, including
      viral hepatitis, chemotherapy-induced hepatotoxicity and leukemic infiltration.
      HCV infection may be suspected to play a relevant role as these patients are
      often heavily transfused after the onset of their hematologic disorder. We have
      therefore examined the role of HCV in 15 children with leukemia who developed
      severe liver damage shortly after the diagnosis of leukemia. All patients were
      tested for HCV-RNA by the polymerase chain reaction at the time of peak SGPT
      elevation and for anti-HCV on serial serum samples taken thereafter. Only one
      patient (6.6%) showed hepatitis C viremia and none developed confirmed anti-HCV
      positivity during follow-up, suggesting that HCV had not played a major role in
      causing these severe episodes of liver necrosis. This is in agreement with
      observations made in non-immunocompromised patients in whom fulminant hepatitis
      is only exceptionally due to HCV.

PMID- 7517748
TI  - Effect of hypothalamic 5,7-dihydroxytryptamine lesion on the anterograde
      transport of serotonin as measured with labeled alpha-methyl serotonin.
AB  - The anterograde axonal transport of serotonin along the medial forebrain bundle
      (MFB) 5 days after unilateral dorsal hypothalamic 5,7-dihydroxytryptamine (5,7
      DHT) lesion was examined in rat brain. Measurements were done using in vivo
      synthesized radioactively labeled alpha-methyl serotonin (used here as a
      serotonin tracer), from i.v. injected labeled alpha-methyl-L-tryptophan, a
      substitute neurotransmitter and analog of serotonin. Data indicated that after
      destruction of the presynaptic terminals with 5,7-DHT, the rate of axonal
      transport of serotonin and/or the rate of serotonin synthesis in the spared
      and/or damaged neurons was increased. The rate of serotonin anterograde transport
      on the lesioned side was above 25 mm/d compared to 12.31 +/- 0.49 mm/d on the
      contralateral side and 12.13 +/- 0.44 mm/d in control (sham injected) rats. The
      difference in rate between the lesioned and control rats was highly significant;
      P < 0.005 (two-tailed t-test). The amount of neurotransmitter anterogradely
      transported along the medial forebrain bundle and/or synthesized in the neurons
      was 18.8 +/- 4.1 times greater on the side of the 5,7-DHT hypothalamic lesion
      than that on the contralateral sides or that found in the saline-injected rats.
      There was no difference in the radioactivity found on the left or right side of
      the medial forebrain bundle in the rats 5 days after lesion in the rostal
      midbrain with 5,7-DHT. Five days after the lesion there was also no difference in
      the anterograde protein transport measured by stereotaxic injection of
      [3H]proline into the dorsal raphe.

PMID- 7517751
TI  - Developmental disability: myths and realities.

PMID- 7517752
TI  - Influenza C in the United Kingdom.

PMID- 7517749
TI  - Neurotrophic effects of testosterone on the medial nucleus of the amygdala in
      adult male rats.
AB  - Our previous reports of major sex differences in the substance P-immunoreactive
      (SPir) innervation of the medial posterior divisions of the bed nucleus of the
      stria terminalis (BST) and medial nucleus of the amygdala in rats raised the
      question of the hormonal regulation of this innervation. We now report the
      results of two experiments which examined the effects of castration of adult
      males on the SPir innervation of these regions. In experiment 2 we asked whether
      castration might also alter the cytoarchitecture of these regions. In experiment
      1 three groups; sham operated (Sham), castrated (C) and castrated plus
      testosterone (C+T) were examined at each of the three survival periods (2, 4 and
      8 weeks) post castration. Animals of the C+T groups each received a 45 mm
      silastic implant of testosterone sc at the time of castration to maintain
      testosterone levels postoperatively. Castration produced a consistent and highly
      significant decrease in the area of dense SPir fiber staining in the posterior
      medial amygdala which became greater with increasing survival. By 8 weeks the
      area of staining was 42% smaller in group C as compared to the matched sham
      operated group. Smaller decreases were seen in the size of the dense field of
      SPir fibers in the posterior part of the dorsomedial BST. Testosterone implants
      maintained the size of the SPir fields of fibers in both the medial amygdala and
      BST, as the areas of staining in the C+T groups were not significantly different
      from those in the Sham groups at any of the 3 survival times. In experiment 2 we
      measured the area and optical density of SPir fiber staining in the medial
      amygdala and medial BST at 8 weeks post-castration. In addition, we measured the
      size of the cell groups within these regions using cresyl-stained sections. As in
      experiment 1, at 8 wks following castration there was a marked decrease in the
      area of dense SPir staining in both the BST and medial amygdala. The sizes of the
      dense fields of fibers were reduced by approximately 23% in the BST and by 40% in
      the posterior medial amygdala. Castration also significantly reduced the optical
      density of staining within the medial amygdala. The major finding of experiment 2
      is that castration affects the cytoarchitecture as well as the SPir staining in
      these areas. In the BST, the cell group BSTMPM receives most of the dense SPir
      innervation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7517750
TI  - Estrogen receptor immunoreactivity in specific brain areas of the prairie vole
      (Microtus ochrogaster) is altered by sexual receptivity and genetic sex.
AB  - The prairie vole is a small rodent with an unusual reproductive strategy. A
      sexually naive female vole requires male contact to initiate the maturation of
      her reproductive functions. Contact with an unfamiliar adult male vole increases
      blood estrogen levels, reproductive tissue weights, and brain nuclear estrogen
      receptor binding levels of female voles. What is not known is: 1) What is the
      precise distribution of estrogen receptor containing neurons in the prairie vole
      brain? 2) Does male induced sexual receptivity alter the distribution or number
      of estrogen receptors in specific brain areas of the female vole? 3) Do male and
      female voles differ in the distribution or number of estrogen receptor containing
      neurons? We compared sexually receptive-male-exposed females, sexually naive
      females, and sexually naive males, for the presence of estrogen receptor
      immunoreactive (ER-IR) neurons in specific cell groups of the brain. The number
      of ER-IR neurons per cell group was counted and the relative amount of
      immunoreactivity per neuron was measured by densitometry. The neuroanatomical
      distribution of estrogen receptor containing neurons in the vole was similar to
      the distribution of estrogen receptors in most rodents. The mean number of ER-IR
      neurons did not differ between naive and male-exposed females. The induction of
      sexual receptivity however significantly decreased the concentration of estrogen
      receptor immunoreactivity per neuron in the medial preoptic nucleus, the medial
      preoptic area, the encapsulated bed nucleus of the stria terminalis, and the
      ventromedial nucleus of the hypothalamus. Compared with naive males, the mean
      number of ER-IR neurons was up to four fold greater in naive females in the
      medial preoptic nucleus, anteroventral periventricular preoptic nucleus, the
      encapsulated bed nucleus of the stria terminalis, the medial amygdala, and the
      ventromedial nucleus of the hypothalamus. Additionally the amount of estrogen
      receptor immunoreactivity per neuron was considerably greater in the medial
      preoptic nucleus, the medial preoptic area, the encapsulated bed nucleus of the
      stria terminalis, and the ventromedial nucleus of the hypothalamus of naive
      females. If the amount of estrogen receptor per cell is a determinant of a
      tissue's responsiveness to estrogen, reduced estrogen receptor immunoreactivity
      in males, and in females exposed to males suggests that they may be less
      responsive to estrogen than naive females. We propose that this reduced estrogen
      receptor immunoreactivity in males is a result of reduced estrogen receptor
      protein levels. Currently, we cannot definitively prove our working hypothesis
      that decreased estrogen receptor immunoreactivity in females exposed to males is
      due to reduced receptor levels, and not due to ligand altered epitope
      availability.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7517754
TI  - Infectious and congenital syphilis in England.

PMID- 7517753
TI  - Poliomyelitis in Azerbaijan.

PMID- 7517755
TI  - AIDS and HIV infection worldwide.

PMID- 7517757
TI  - Improved fractionation of sialylated glycopeptides by pellicular anion-exchange
      chromatography.
AB  - The glycoprotein bovine fetuin was treated with trypsin and the Asn-81 tryptic
      glycopeptide was purified (90% pure by Edman sequencing) by reversed-phase
      chromatography (RP-HPLC). The Asn-81 glycopeptide, which eluted as a single peak
      by RP-HPLC, was separable into five peaks on the NucleoPac PA100 column, a
      pellicular anion-exchange column. Each of the five Asn-81 glycopeptide peaks was
      shown to contain N-linked oligosaccharides by treatment of each peak with peptide
      N4-(N-acetyl-beta-D-glucosaminyl) asparagine amidase F (PNGase F) and subsequent
      oligosaccharide analysis by high-pH anion-exchange chromatography with pulsed
      amperometric detection. High-pH anion-exchange chromatography-pulsed amperometric
      detection oligosaccharide analysis revealed that each peak contained a different
      population of sialylated N-linked oligosaccharides. Hence each peak contained a
      different group of glycopeptide glycoforms. It was observed that the longer the
      retention time of the Asn-81 glycopeptide peak on the anion-exchange column, the
      greater the oligosaccharide sialylation. Two glycopeptide peaks which differed in
      their distribution of disialylated oligosaccharides demonstrated that the
      glycopeptide separation was a result of something more than gross differences in
      sialic acid content. The two other N-linked tryptic glycopeptides of fetuin were
      also separated into multiple peaks on the NucleoPac PA100 column and these
      separations were shown to be due to differences in oligosaccharide sialylation.
      The separations of the three fetuin N-linked glycopeptides demonstrate that
      pellicular anion-exchange chromatography offers improved separation speed and
      resolution for the separation of sialylated glycopeptides.

PMID- 7517759
TI  - Inflammatory pseudotumor of the urinary bladder with an aberrant expression of
      cytokeratin.
AB  - A case of inflammatory pseudotumor of the urinary bladder in a 47 year old
      Japanese male patient is presented. Inflammatory pseudotumor of the urinary
      bladder is a benign but rare proliferative lesion of the submucosal stroma,
      easily mistaken for a malignant neoplasm. Based on the clinical diagnosis of
      bladder cancer by cystoscopy and magnetic resonance imaging (MRI), urologists
      started chemotherapy before results of the histological report were available
      which described inflammatory pseudotumor on the biopsy. Biopsied materials showed
      marked proliferation of irregularly bundled spindle cells, varied in size and
      shape and separated in severe loose myxoid stroma with moderate infiltration of
      the inflammatory cells and capillary proliferations. At a glance, these findings
      resemble the sarcomatous pattern. However neither severe nuclear atypism nor
      atypical mitoses were present. Immunohistochemically, these spindle cells, which
      were positive for vimentin and alpha-smooth muscle actin, showed a diffuse
      aberrant expression of cytokeratin. Some of them were positive for
      phosphotungstic acid hematoxylin. Electron microscopy revealed only the
      fibroblasts. No recurrence has been observed for 10 months. These findings
      indicate that inflammatory pseudotumor is a benign mesenchymal lesion that must
      be discriminated from true sarcoma to avoid subjecting the patient to unnecessary
      therapy. Only careful histological examination can enable a successful diagnosis.

PMID- 7517756
TI  - Capillary zone electrophoresis of synthetic opioid and tachykinin peptides.
AB  - Capillary zone electrophoresis was performed on fourteen synthetic opioid
      peptides and one tachykinin peptide (substance P = SP) at pH values of 2.5, 5.5
      and 8.5 to rationalize the electrophoretic behavior of these neuropeptides. A
      plot of the theoretical q/M(r)2/3 values (where q = peptide charge) calculated
      across the pH range of 1 to 10 for these peptides was used to understand and to
      predict their separation. The experimentally determined electrophoretic
      mobilities (mu) were correlated to the estimate of the relative mu predicted by
      q/M(r)2/3 and by [ln (q + 1)]/n0.43 (where n = number of constituent amino
      acids), where q values were calculated using amino acid pKa values for an
      isolated amino acid and for an amino acid in a peptide. In general, relatively
      high correlations were obtained with either mathematical expression and with both
      sets of amino acid pKa values for data at a single pH value. However, the
      combination of the former expression and the adjusted pKa values gave the best
      prediction of electrophoretic behavior when data for the three pH values were
      correlated across these different separation conditions.

PMID- 7517758
TI  - Neoplastic and non-neoplastic intermediate trophoblasts: an immunohistochemical
      and ultrastructural study.
AB  - Five cases of non-molar trophoblastic disease including one placental site
      trophoblastic tumor (PSTT), two exaggerated placental sites and two
      choriocarcinomas were compared with each other and with normal chorionic villi
      and placental site. This involved light microscopic, immunohistochemical and
      ultrastructural studies. Comparison of PSTT with choriocarcinoma suggested that
      the former represented a neoplastic transformation of placental site intermediate
      trophoblast. The PSTT showed a characteristic immunohistochemical distribution of
      human placental lactogen and human chorionic gonadotropin, resembling that of the
      placental site intermediate trophoblast. Placental site trophoblastic tumor cells
      were also characterized ultrastructurally by prominent perinuclear filaments,
      abundant rough endoplasmic reticulum, or both. Infiltrating intermediate
      trophoblasts in exaggerated placental sites were similar to PSTT cells rather
      than normal placental site intermediate trophoblasts. However cells with
      vacuolated cytoplasm or spindle-shaped intermediate trophoblastic cells were
      observed more frequently in the PSTT than the exaggerated placental sites. The
      intermediate trophoblastic cells in the choriocarcinomas showed a morphologically
      transitional form from cytotrophoblastic cell to syncytiotrophoblastic cell, but
      did not share unique ultrastructural similarities with placental site
      intermediate trophoblasts.

PMID- 7517760
TI  - Mixed tumor of the external auditory canal.
AB  - A mixed tumor with apocrine differentiation seen in the external auditory canal
      of a 39 year old male is reported. The well demarcated polypoid tumor showed
      proliferation of elongated gland-like or duct-like structures lined by two rows
      of epithelial cells, occasionally accompanied by foci of keratinization. There
      were fat cells in the myxoid stroma, in which no chondroid elements were seen.
      This neoplasm is considered to have arisen from the ceruminous gland, the
      modified apocrine gland of the skin.

PMID- 7517762
TI  - Fibronectin and tenascin in rat tracheal wound healing and their relation to cell
      proliferation.
AB  - To investigate the relationship between cell proliferation and distribution of
      fibronectin and tenascin during wound healing, light and electron microscopy and
      immunohistochemistry for fibronectin, tenascin, and 5-bromodeoxyuridine (BrdU)
      were performed following mechanical injury of rat trachea. Tenascin staining
      appeared 18 h after curettage, when the percentage of BrdU-positive nuclei was
      maximal in the epithelium. Once tenascin appeared, the labeling index of BrdU
      positive epithelial nuclei decreased rapidly. Distribution of tenascin was
      restricted to granulation tissue in curetted areas which were covered with
      regenerating epithelium, while fibronectin stained diffusely in both curetted and
      non-curetted areas. Analysis of the relative intensity of fibronectin and
      tenascin staining showed that decreases of fibronectin staining were followed by
      increasing tenascin staining. It is proposed that fibronectin and tenascin may
      contribute differently to tissue repair in the trachea by interfering with cell
      proliferation of epithelial cells and fibroblasts.

PMID- 7517761
TI  - Sarcomatoid carcinoma of the urinary tract.
AB  - Sarcomatoid carcinoma is a rare variant of malignant tumor arising from the
      urinary tract. This tumor had been termed carcinosarcoma because of its
      carcinomatous and sarcomatous components. There is still some confusion in the
      terminology between true carcinosarcoma and sarcomatoid carcinoma; however, the
      latter is now regarded as primarily a malignant epithelial tumor with
      pseudosarcomatous transformation. Four cases of sarcomatoid carcinoma arising
      from the urinary tract are reported. The patients were a 77 year old female, and
      three males aged 62, 69 and 80 years. All but the eldest patient complained of
      gross hematuria. Surgical removal was performed in the younger three cases, and
      an autopsy was done in the remaining case. All the tumors were macroscopically
      polypoid. Histopathologic examination revealed fasciculated spindle-cell tumors
      with myxoid stroma or malignant fibrous histiocytoma-like spindle cell tumors.
      The epithelial nature was proven in these sarcomatous cells by
      immunohistochemical and/or electron-microscopic examinations. Only a small amount
      of squamous cell carcinoma components was also evident in the latter three cases.
      Although the younger three patients were alive at 44, 23 and 39 months' follow
      up, respectively, constant careful monitoring is recommended.

PMID- 7517763
TI  - Nucleolar organizer regions and PCNA expression in prostatic cancers.
AB  - Argyrophilic nucleolar organizer regions (AgNOR) of 79 prostatic adenocarcinomas,
      and an immunohistochemical stain using a monoclonal antibody against
      proliferating cell nuclear antigen (PCNA) of 54 prostatic adenocarcinomas,
      obtained by needle biopsy and transurethral resection of the prostate between
      1986 and 1989, were investigated. A morphological classification was devised to
      count silver dots based on the relations between intra- and extra-nucleolar AgNOR
      (type A, B, C and D). Total AgNOR counts were significantly higher in carcinoma
      (4.2 +/- 1.57) than in the benign prostatic lesions (1.90 +/- 0.24). Count
      differences of AgNOR were evident in histological differentiation, nuclear
      anaplasia, and presence of nucleoli, mitosis, lymphatic invasion and vascular
      invasion. Higher total AgNOR counts were almost always associated with type B and
      C AgNOR (intranucleolar AgNOR), but were not associated with type A (nucleolus
      without small dot) nor type D (extra-nucleolar AgNOR). This study shows the
      diagnostic value of AgNOR in prostatic cancer, and the importance of
      morphological classification of AgNOR. The survival of patients with higher AgNOR
      counts (> or = 4.3) was significantly poorer than survival of those with lower
      AgNOR counts (< 4.3). Significantly more PCNA positive cells were identified in
      cancer by immunohistochemical stain and correlated with the presence of mitosis,
      but there was no significant difference in survival rate groups classified by
      PCNA positivity. It is also suggested that PCNA can be a useful marker of cell
      proliferation in prostatic lesions, but the AgNOR counts were diagnostically and
      prognostically more valuable than immunohistochemical PCNA in prostatic lesions.
      The correlation between AgNOR and PCNA immunoreactivity was not significant.

PMID- 7517764
TI  - An autopsy case of hepatic sarcomatoid tumor: immunohistochemical comparison with
      a sarcomatous component of hepatocellular carcinoma.
AB  - A case of primary hepatic tumor exclusively composed of malignant cells with
      sarcomatous features is described and compared immunohistochemically with two
      cases of hepatocellular carcinoma (HCC) with a sarcomatous component. More than
      30% of HCC cells were positively stained with anti-cytokeratin (CAM5.2), anti
      albumin, anti-fibrinogen and anti-alpha 1-antitrypsin antibodies, and some with
      anti-epithelial membrane antigen. The present sarcomatoid tumor and the
      sarcomatous component with HCC showed similar immunohistochemistry; many tumor
      cells were strongly immunoreactive for vimentin and some positive for
      cytokeratin, albumin, fibrinogen and alpha 1-antitrypsin. Other
      immunohistochemical markers, indicating specific differentiations to lineage of
      macrophages, muscle cells, glial cells, endothelial cells and so forth, were not
      detected in sarcomatous tumor cells of all cases. These findings suggest that the
      present sarcomatoid tumor would belong to an anaplastic sarcomatous variant of
      HCC.

PMID- 7517765
TI  - Phenotypic comparison between rhizosphere and clinical isolates of Burkholderia
      cepacia.
AB  - The phenotypic characteristics of four Burkholderia cepacia strains isolated from
      the rhizosphere and the clinical environment were compared. Tests included
      optimum growth temperature, utilization of carbon sources, production of HCN,
      indole-3-acetic acid (IAA) and siderophores, proteolytic activity, nitrogen
      fixation, inhibition of some phytopathogenic fungi, adherence to human mucosal
      and plant root epithelia, and greenhouse-based plant-growth promotion experiments
      using cucumber (Cucumis sativus). Results indicated that the strains of B.
      cepacia isolated from the rhizosphere differ markedly from their clinical
      counterparts. Strains isolated from the rhizosphere grew over a wider temperature
      range, fixed nitrogen and produced IAA, did not produce proteases, displayed a
      wider antibiosis against the phytopathogenic fungi studied, did not adhere to
      human uroepithelial cells, promoted growth of C. sativus and only produced a
      hydroxamate-like siderophore. In contrast, clinical isolates could not fix
      nitrogen or produce IAA, produced proteases, adhered to human uroepithelial
      cells, did not promote the growth of C. sativus and, in addition to a hydroxamate
      like siderophore, produced pyochelin and salicylate siderophores. All four
      isolates exhibited the ability to adhere to the root tissue of C. sativus and
      were unable to produce HCN.

PMID- 7517766
TI  - Frequencies of lipopolysaccharide core types in Escherichia coli strains from
      bacteraemic patients.
AB  - We have investigated the distribution of the various core types (R1, R2, R3, R4
      and K-12) in 138 Escherichia coli isolates obtained from positive blood cultures.
      Rabbit antisera, raised against five rough strains expressing the respective core
      types, were made monospecific by extensive absorption. The reactivity of the
      antisera was tested in ELISA with bacterial cells that had been autoclaved for
      full exposure of core epitopes. One hundred and thirty strains could be typed
      directly, while eight strains required prior digestion with proteinase K for
      removal of cross-reactions. Ninety-four of the strains (68%) expressed the R1
      type, and 9 (6.5%), 12 (8.7%), 7 (5.1%) and 3 (2.2%) strains expressed the R2,
      R3, R4 and K-12 core types, respectively. An R1R4 mixed core type, hitherto not
      yet described, was found in 13 (9.4%) strains. Results obtained with polyclonal
      antisera were in agreement with those obtained with monoclonal antibodies to the
      R1, R2 and R3 core types. Core typing may serve as an additional serological
      marker next to conventional typing of O-, H- and K-antigens.

PMID- 7517767
TI  - The psi operon of Rhizobium leguminosarum biovar phaseoli: identification of two
      genes whose products are located at the bacterial cell surface.
AB  - We have delineated three short open reading frames, psiA, ORF-P and psiB within
      the psi operon of Rhizobium leguminosarum biovar phaseoli. psiA, in a multi-copy
      plasmid, causes inhibition of exopolysaccharide synthesis in R. leguminosarum. In
      addition, the suppression of exopolysaccharide synthesis due to the multi-copy
      psiA caused R. leguminosarum strains to stain with the dye calcofluor, a response
      that does not occur with wild-type strains of this species. Insertions of a
      defective phoA gene (lacking its promoter, ribosomal binding site and leader
      sequence) into psiA and psiB were isolated and the precise locations of the
      insertions were established. PsiA-PhoA and PsiB-PhoA protein fusions were found
      to express alkaline phosphatase activity indicating that PsiA and PsiB span the
      inner membrane or are translocated across it.

PMID- 7517769
TI  - The complex role of nitric oxide in the pathophysiology of focal cerebral
      ischemia.
AB  - Nitrogen monoxide (NO) has recently emerged as an important mediator of cellular
      and molecular events which impacts the pathophysiology of cerebral ischemia.
      Although tempting to ask whether NO is "good or bad" for cerebral ischemia, the
      question underestimates the complexities of NO chemistry and physiology as well
      as oversimplifies the pathophysiology of focal cerebral ischemia. Important
      vascular and neuronal actions of NO have been defined which both enhance tissue
      survival and mediate cellular injury and death, and these will be reviewed.
      Strategies which modify NO synthesis and/or metabolism may someday assume
      therapeutic importance, but not until the tissue compartments generating NO, the
      activities of the enzymes that are inducibly and constitutively expressed, and
      the redox state of NO during the stages of ischemic injury, are defined with
      greater precision. Our knowledge of these processes is rudimentary. This review
      will summarize the evidence from animal models which supports an emerging role
      for NO in ischemic pathophysiology. Important aspects of NO synthesis and
      inhibitors of this process will also be discussed.

PMID- 7517771
TI  - Properties of single calcium-activated potassium channels of large conductance in
      rat hippocampal neurons in culture.
AB  - Patch-clamp recordings were made on rat hippocampal neurons maintained in
      culture. In cell-attached and excised inside-out and outside-out patches a large
      single-channel current was observed. This channel had a conductance of 220 and
      100 pS in 140 mM [K+]i/140 mM [K+]o and 140 mM [K+]i/3 mM [K+]o respectively.
      From the reversal potential the channel was highly selective for K+, the PK+/PNa+
      ratio being 50/1. Channel activity was voltage-dependent, the open probability at
      100 nM [Ca2+]i increasing by e-fold for a 22 mV depolarization. It was also
      dependent on [Ca2+]i at both resting and depolarized membrane potentials. Channel
      open states were best described by the sum of two exponentials with time
      constants that increased as the membrane potential became more positive. Channel
      activity was sensitive to both external (500 microM) and internal (5 mM)
      tetraethylammonium chloride. These data are consistent with the properties of
      maxi-K+ channels described in other preparations, and further suggest a role for
      maxi-channel activity in regulating neuronal excitability at the resting membrane
      potential. Channel activity was not altered by 8-chlorophenyl thio cAMP,
      concanavalin A, pH reduction or neuraminidase. In two of five patches lemakalim
      (BRL 38227) increased channel activity. Internal ruthenium red (10 microM)
      blocked the channel by shortening the duration of both open states. This change
      in channel gating was distinct from the 'mode switching' seen in two patches,
      where a channel switched spontaneously from normal activity typified by two open
      states to a mode where only short openings were represented.

PMID- 7517772
TI  - Retrograde axonal transport of the alpha-subunit of the GTP-binding protein GZ in
      mouse sciatic nerve: a potential pathway for signal transduction in neurons.
AB  - We have utilized antibodies against the alpha subunit of GZ in fluorescence
      immunohistochemistry to determine whether this GTP-binding protein can
      translocate along nerves by intra-axonal transport. After ligation of the mouse
      sciatic nerve we found an increase in GZ-like immunoreactivity on the proximal
      and distal side with time, suggesting that the alpha subunit undergoes orthograde
      axonal transport and also returns to the cell body by retrograde axonal transport
      in the sciatic nerve. Unlike the retrograde transport of Gi alpha, shown in a
      previous study to be present in most sciatic axons, GZ alpha only accumulated in
      a subpopulation of axons, suggesting that different G-proteins could convey
      information specific to neuronal subtypes. These results support our proposal
      that GZ may play a second messenger role in communicating information from the
      terminals back to cell bodies. Gi alpha and GZ alpha may be representative of
      relatively stable signalling molecules by which the signal from some neurotrophic
      molecules can be translocated from the neuron periphery to the cell body without
      the need for the retrograde transport of the neurotrophic factor itself.

PMID- 7517770
TI  - The extracellular matrix molecule janusin regulates neuronal morphology in a
      substrate- and culture time-dependent manner.
AB  - Janusin is an extracellular matrix glycoprotein with structural homology to
      tenascin. In search of extracellular matrix components which govern the
      differentiation of neurons in the central nervous system, we have investigated
      the influence of janusin on the differentiation of hippocampal neurons in vitro.
      Janusin coated onto nitrocellulose was a good substrate for attachment of cell
      bodies and neurite outgrowth after 21 h of culture. Most cells exhibited a
      polarized morphology with one long major neurite and one or two short minor
      neurites. When janusin was coated onto a polyornithine-conditioned plastic
      surface, it increased the polarity of neurons in that the length of major
      neurites was increased and the length and number of minor neurites were decreased
      when compared with the control polyornithine-conditioned plastic without janusin.
      As we have shown before for tenascin, laminin and fibronectin, polarization was
      preceded by an increase in the number and length of all neurites during the first
      hours after cell plating. This study therefore adds janusin to the increasing
      number of extracellular matrix glycoproteins which promote axonal but not
      dendritic growth.

PMID- 7517773
TI  - Up-regulation of neurotensin mRNA in the rat striatum after acute methamphetamine
      treatment.
AB  - The effect of acute subcutaneous administration of methamphetamine on the
      expression of neurotensin mRNA was investigated in the adult rat striatum. At
      different time points (2, 6 and 24 h) following drug administration rats were
      killed, and mRNA levels were quantified both on films and emulsion-dipped tissue
      sections from two striatal levels. Two hours after methamphetamine injection, a
      dramatic increase in neurotensin mRNA levels was detected in different areas of
      the striatum at both rostral and caudal levels. Numerous positive cells were
      observed in the dorsomedial, dorsolateral and ventrolateral parts of the
      striatum. This up-regulation reflected an increase both in the number of cells
      expressing neurotensin mRNA and in the mean mRNA levels. This increase was still
      present after 6 h and was similar to the 2 h treated group at the rostral level
      of the striatum, but lower at the caudal one. Twenty-four hours after
      methamphetamine injection, neurotensin mRNA levels were back to control values,
      or in some areas even below. A strong increase in neurotensin mRNA-expressing
      cells was also seen in the olfactory tubercle, and the time-course was similar to
      the one observed in the striatum. In a second set of experiments, the effect of
      methamphetamine was evaluated on adjacent striatal sections hybridized with
      probes directed against neurotensin and substance P mRNAs, respectively. Two
      hours after drug administration, a significant increase in the levels of both
      peptide mRNAs was observed (+190% for neurotensin, +80% for substance P). These
      results demonstrate that methamphetamine is able to induce a dramatic, rapid and
      transient increase in striatal neurotensin mRNA levels, which may partly account
      for the elevation in neurotensin peptide levels observed in the striatonigral
      pathway after methamphetamine. The different anatomical localization of
      neurotensin mRNA-expressing cells observed after haloperidol and methamphetamine
      treatments, as well as the fact that the D1 receptor antagonist SCH-23390 is able
      to counteract the effect of methamphetamine but not that of haloperidol on
      neurotensin mRNA expression, suggests that there are at least two different
      subpopulations of neurotensin cells in the striatum. One population is regulated
      via D1 receptors and projects to the substantia nigra pars reticulata. The second
      is sensitive to D2 receptor stimulation and may project to the globus pallidus
      and/or may represent interneurons.

PMID- 7517768
TI  - [Oligodeoxyribonucleotides complementary to sections of the mollicute ribosomal
      operon as transcription inhibitors in vitro].
AB  - Antisense oligodeoxyribonucleotides have been studied for their effect on the
      transcription in vitro in mollicutes. A synthetic fragment of DNA [symbol: see
      text] complementary to that part of DNA which codes the 1510-1521 area of the 3'
      terminal sequence 16S-pRNA of all mollicutes was used in the study as well as its
      modifications by imidasophenasine derivatives: [symbol: see text], [symbol: see
      text] [symbol: see text]. Maximal inhibition of the mollicute transcription in
      vitro was observed with 100 nM oligonucleotide concentration. Lower or higher
      concentrations were less effective. Transcription initiated by RNA-polymerase of
      M. fermentans PG-18 (a mollicute strain referring to AIDS disease) proved to be
      the most sensitive to the effect of modified oligonucleotide: it was inhibited by
      75-80%. It is concluded that modified oligonucleotides exert a dual effect on
      transcription: firstly, they participate in nonspecific interaction with RNA
      polymerase which induces insignificant inhibition of transcription and, secondly,
      they complementary interact with homologous sections of one-stranded DNA-matrix
      and block the RNA synthesis. Binding of modified oligonucleotides with DNA is
      rather strong.

PMID- 7517774
TI  - Iris claw lens: anterior and posterior iris surface fixation in the absence of
      capsular support during penetrating keratoplasty.
AB  - BACKGROUND: Intraocular lens implantation in eyes with pseudophakic or aphakic
      corneal edema and insufficient posterior capsular support presents a surgical
      challenge. The iris claw lens has the advantage that it can be fixated to the
      iris without sutures because the peripheral iris is incarcerated between the
      claws. METHODS: We present the results of a study with implantation of an iris
      claw lens in combination with penetrating keratoplasty in 19 eyes of 19 patients
      with pseudophakic or aphakic corneal edema which lacked posterior capsular
      support. The lens was fixated on the anterior iris surface (12 eyes) or posterior
      iris surface (seven eyes). RESULTS: Mean follow-up time was 11.8 months (7 to 21
      months). All grafts remained clear. One patient was lost for follow up after 3
      months. Visual acuity improved in 83% of the patients. Twenty-eight percent of
      the patients had a visual acuity of > or = 20/40. Complications such as pigment
      dispersion, glaucoma, peripheral synechiae, and lens decentration were rare.
      CONCLUSIONS: We feel iris claw lens implantation combined with penetrating
      keratoplasty is a safe alternative to achieve pseudophakia in eyes with corneal
      edema and inadequate posterior capsular support.

PMID- 7517777
TI  - Severe ocular trauma without corneal rupture after radial keratotomy: case
      reports.
AB  - The vulnerability of the ocular coat to trauma following radial keratotomy is an
      issue of concern to both patients and physicians. Herein, we report two cases of
      eyes which were exposed to severe trauma after previously undergoing radial
      keratotomy procedures. In the first case, a woman sustained multiple facial bone
      fractures in a fatal airplane crash. In the second case, a man was involved in a
      case of blunt ocular trauma involving a high velocity racquetball. Rupture of the
      ocular coat did not occur in either case.

PMID- 7517775
TI  - Diffractive smoothing of excimer laser ablation using a defocused beam.
AB  - OBJECTIVE: To determine if excimer laser myopic ablation with a defocused laser
      image produces a smoother ablation profile than does focused laser light.
      METHODS: An ArF excimer laser was used to ablate a 5.00-diopter myopic correction
      in test blocks using both a contracting and expanding iris aperture. Defocused
      ablation was performed using a contracting iris aperture by translating the
      target away from the laser source. A confocal laser scanning microscope was used
      to analyze the surface smoothness at 55x and 275x magnifications. RESULTS: The
      confocal laser scanning micrographs revealed a series of sharply demarcated
      concentric ridges in the focused ablation, and less prominent, slightly wavy
      lines in the defocused ablation performed with a contracting aperture. The
      focused ablation with an expanding aperture also created concentric ridges toward
      the periphery, but with slightly smoother edges.

PMID- 7517778
TI  - Radial thermokeratoplasty is inadequate for overcorrection following radial
      keratotomy.

PMID- 7517776
TI  - Inverse arcuate incision: a new approach to the correction of astigmatism.
AB  - Standard concentric arcuate transverse corneal relaxing incisions flatten the
      meridian incised and steepen the meridian 90 degrees away, a phenomenon
      designated "coupling". We have demonstrated a new method of reducing the steep
      corneal curvature without inducing coupling, by utilizing both transverse and
      radial components of an inverse arcuate incision. This technique has been found
      useful in cases of myopic astigmatism because it reduces the myopic spherical
      equivalent, which is left unchanged by standard arcuate incisions, without having
      to place radial incisions.

PMID- 7517779
TI  - Traumatic corneal abrasions following photorefractive keratectomy.
AB  - BACKGROUND: During excimer laser photorefractive keratectomy, central Bowman's
      layer and superficial stroma are removed. A potential disadvantage of this
      technique is whether proper epithelization of the cornea will occur in the event
      of a corneal abrasion. A potential advantage of photorefractive keratectomy over
      radial keratotomy in the event of blunt trauma is the presumably sound structural
      integrity of the cornea following superficial removal of stroma in
      photorefractive keratectomy compared to the weakened cornea following deep
      incisions in radial keratotomy. METHODS: We report two patients who sustained
      corneal abrasions from blunt trauma to the eye and orbit following
      photorefractive keratectomy--one following a fist injury and the other following
      a karate kick. RESULTS: In both patients, the corneal abrasions healed without
      incident and without recurrent erosions and both corneas remained intact.
      CONCLUSIONS: Corneal abrasion following trauma in two patients who has undergone
      photorefractive keratectomy healed as expected in a normal cornea. Although it is
      uncertain whether the trauma in these patients would have been sufficient to
      rupture radial keratotomy incisions, as would be expected from a superficial
      photorefractive keratectomy, the corneas remained intact following blunt trauma.

PMID- 7517781
TI  - Intraoperative pachometry during automated lamellar keratoplasty: a preliminary
      report.
AB  - BACKGROUND: The hinge technique greatly improves the results of automated
      lamellar keratoplasty but makes it impossible to measure the thickness of the
      corneal cap with a micrometer. We developed a technique of measuring cap and
      stromal disc thickness with a pachometer and compared the results with those
      obtained with a micrometer. METHODS: Measurements of the thickness of the stromal
      disc and/or corneal cap were taken with the Mitutoyo micrometer and the Chiron
      Corneo-Gage System III pachometer in five myopic and three hyperopic cases
      undergoing automated lamellar keratoplasty with complete cap resection. The
      intended postoperative refraction was plano. Postoperative refractions were taken
      at two months. RESULTS: In most cases, the corneal cap measured thinner while the
      stromal disc measured thicker by the micrometer than by the pachometer because of
      the hydration status of the stromal bed. In both myopic and hyperopic cases, the
      thickness measurements taken with the pachometer correlated better with the
      postoperative spherical equivalent values than those taken with the micrometer.
      CONCLUSIONS: The thickness measurement of corneal resections by both micrometry
      and pachometry is greatly influenced by tissue hydration status. When hydration
      is similar, the pachometer provides more accurate thickness readings than does
      the micrometer, as determined by correlations with intended refractive results.

PMID- 7517782
TI  - Does the progressive increasing effect of radial keratotomy (hyperopic shift)
      correlate with undetected early keratoconus?
AB  - Keratoconus suspect is a new clinical entity revealed by videokeratography. We
      perform systematic videokeratography on all candidates for refractive surgery,
      and have identified a keratoconus suspect in more than 10% of eyes. A lot of
      patients with undetected early keratoconus have been operated on since 1980. We
      suggest a possible correlation between early keratoconus suspect and the
      hyperopic shift following radial keratotomy. Our arguments are based on clinical
      observations, knowledge about pathogenesis of keratoconus and the mechanism of
      action of radial keratotomy, and epidemiological considerations.

PMID- 7517783
TI  - Refractive corneal surgery with the Draeger rotary microkeratome in human cadaver
      eyes.
AB  - BACKGROUND: Instrumentation for performing a uniform lamellar keratoplasty has
      been undergoing various stages of refinement. Reliable reproduction and uniform
      thickness and diameter of lamellar resections is required before lamellar
      refractive keratoplasty can be considered safe and effective. METHODS: The
      authors used the Draeger rotary microkeratome with mechanical blade advance for
      lamellar dissections in 61 human cadaver eyes prepared by injecting Swinger
      Kornmehl (SK) solution into the anterior chamber to a pressure of 35 to 40 mm Hg
      and by soaking for 30 minutes in SK solution. Spacer sizes of 0.25 to 0.40 units
      were utilized using an anterior lamellar disc diameter estimate between 8.0 and
      8.5 mm and a stromal lamellar disc diameter estimate between 5.5 and 6.5 mm.
      Preoperative pachometry, anterior and stromal lamellar disc thicknesses, and
      anterior and stromal lamellar disc diameters were measured. RESULTS: The Draeger
      unit created anterior lamellar thickness between 100 and 268 microns. Stromal
      lamellar disc thicknesses were consistently between 90 and 161 microns. The
      continuous, unidirectional, rotary blade and the uniform mechanical advance of
      the instrument produced a generally uniform bed as evaluated by scanning electron
      microscopy, although undulations were still present. CONCLUSION: The Draeger
      microkeratome produced regular lamellar dissections; however, predictability of
      the thickness of the lenticules varied 10% to 20%, and of the diameter, 1.5% to
      15%. Predictability improved with experience. This variability may reduce
      predictability of refractive outcome.

PMID- 7517784
TI  - First ever eye donor: a lesson from Indian history and Kannappa Nayanar.

PMID- 7517780
TI  - Viability of bacteria in glycerin and ethanol preserved sclera.
AB  - BACKGROUND: Sclera is commonly preserved in glycerin or ethanol before being used
      for ophthalmic surgery. The purpose of this study was to determine the ability of
      bacteria to survive in sclera preserved in glycerin or ethanol. METHODS: Fresh
      sclera was inoculated with Staphylococcus aureus, Streptococcus pneumoniae, or
      Pseudomonas aeruginosa and transferred to preservative vials containing glycerin,
      95% ethanol, or trypticase soy broth (control) and stored at room temperature.
      Pieces of sclera were removed from preservative at designated intervals over a 14
      day period. The sclera was then homogenized, plated on blood agar, and incubated
      at 37 degrees C. Colonies were counted at 24, 48, and 72 hours. RESULTS: S.
      pneumoniae, P. aeruginosa, and S. aureus were recovered from glycerin preserved
      sclera for up to 12 hours, 1.5 days, and 8 days, respectively. No bacteria was
      recovered from the ethanol preserved sclera. CONCLUSIONS: Bacteria cannot be
      recovered from ethanol preserved sclera but can survive in glycerin preserved
      sclera for at least 8 days. Ethanol may offer advantages over glycerin as a
      scleral preservative due to its greater antibacterial activity.

PMID- 7517785
TI  - Optimists predict photorefractive keratectomy approval in 1994.

PMID- 7517786
TI  - NMR studies of the FK506 binding protein bound to a spin-labeled ascomycin
      analog.

PMID- 7517787
TI  - Cloning of a complementary DNA that encodes an acidic chitinase which is induced
      by ethylene and expression of the corresponding gene.
AB  - A complementary DNA encoding an ethylene-inducible acidic chitinase of azuki bean
      (Vigna angularis) was isolated, and its complete nucleotide sequence was
      determined. The nucleotide and deduced amino-acid sequence were very similar to
      those of an acidic chitinase from cucumber leaves that had been infected with
      tobacco necrosis virus. The mRNA for the acidic chitinase was not detected in
      leaves of azuki bean that had not been treated with ethylene, but it appeared 3 h
      after initiation of treatment with ethylene and its level gradually increased
      over a period of 19 h. The mRNA also accumulated in response to salicylate or
      wounding. The expression of the gene in response to wounding was suppressed by
      2,5-norbornadiene, but that in response to salicylate was not affected by this
      inhibitor.

PMID- 7517788
TI  - Cloning and sequencing of cDNA for glycolate oxidase from pumpkin cotyledons and
      northern blot analysis.
AB  - A cDNA clone for glycolate oxidase (EC 1.1.3.1) was isolated by an immunochemical
      method from a cDNA expression library constructed from poly(A)+-RNA of green
      pumpkin cotyledons. The analysis of in vitro transcription-translation products
      of the cDNA insert revealed that the cDNA clone contained the complete coding
      region for glycolate oxidase. The entire insert of the cDNA was 1,440 nucleotides
      in length and encoded 367 amino acid residues, equivalent to a molecular mass of
      40,353 daltons. The amino acid sequence of the C-terminal tripeptide was Pro-Arg
      Leu, which is slightly different from the proposed signal for targeting to
      microbodies, Ser-Lys/Arg/His-Leu. Characteristic hydrophilic domains observed in
      the C-terminal regions of most microbody proteins were found in the deduced
      sequence of glycolate oxidase by hydropathy analysis. Immunoblot analysis showed
      that the amount of glycolate oxidase was low in dark-grown cotyledons and
      increased during greening of pumpkin cotyledons. Northern blot analysis showed
      that the probe could hybridize with a single 1.5-kb species of mRNA from pumpkin
      cotyledons and that the amount of the hybridizable mRNA increased dramatically
      during greening of the cotyledons. This observation indicates that the induction
      of glycolate oxidase during greening of the cotyledons is due to an increase in
      the level of the mRNA.

PMID- 7517789
TI  - Structure of the gene for an auxin-binding protein and a gene for 7SL RNA from
      Arabidopsis thaliana.
AB  - A genomic clone encoding an auxin-binding protein (ABP) from the endoplasmic
      reticulum was isolated from Arabidopsis thaliana. The ABP gene consisted of 5
      exons and 4 introns and encoded a polypeptide of 198 residues. A gene encoding
      the 7SL RNA of the signal recognition particle was located downstream of the ABP
      gene.

PMID- 7517790
TI  - Ventricular arrhythmias induced by chemically modified intrinsic cardiac
      neurones.
AB  - OBJECTIVE: The aim was to investigate whether intrinsic cardiac neurones can be
      involved in the genesis of ventricular arrhythmias. METHODS: Nicotinic,
      muscarinic, beta adrenergic, peptidergic, and amino acidergic agonists, as well
      as purinergic compounds, were individually administered in microliter quantities
      adjacent to spontaneously active in situ right atrial neurones in 57
      anaesthetised dogs before and after acute decentralisation. RESULTS: Ventricular
      arrhythmias were induced in one third of the dogs following neurochemical
      administration. Ventricular arrhythmias are induced much less frequently when
      intrathoracic extracardiac neurones are modified chemically. Salvos of
      ventricular premature contractions or ventricular tachycardias were elicited when
      intrinsic cardiac neurones were modified locally applied nicotine, bethanechol,
      isoprenaline, angiotensin II, bradykinin, substance P, vasoactive intestinal
      polypeptide, glutamate, or adenosine. In 60% of those instances in which
      intrinsic cardiac neuronal activity was modified by a neurochemical, ventricular
      arrhythmias were elicited. When arrhythmias were induced, activity generated by
      chemically modified intrinsic cardiac neurones increased from 0.7(SD 0.2) to
      2.2(0.4) impulses.s-1 (p < 0.05). Following decentralisation of the intrinsic
      cardiac nervous system, repeat administration of the same neurochemicals into the
      same loci elicited ventricular arrhythmias in 42% of those dogs in which
      ventricular arrhythmias had been elicited previously. Neuronal activity increased
      [0.8(0.5) to 2.1(0.6) impulses.s-1; p < 0.05] in 86% of these instances.
      CONCLUSIONS: Intrinsic cardiac neurones can be involved in the genesis of
      ventricular arrhythmias.

PMID- 7517791
TI  - Effects of purified perforin and granzyme A from cytotoxic T lymphocytes on
      guinea pig ventricular myocytes.
AB  - OBJECTIVE: Involvement of cytotoxic T lymphocytes (CTL) in heart transplant
      rejection as well as in viral myocarditis is well established, but the precise
      mechanisms whereby infiltrating CTL damage the myocardium are unknown. The aim of
      the study was to investigate how CTL derived perforin, the serine protease
      granzyme A, and the combination of both, damage guinea pig ventricular myocytes.
      METHODS: Action potentials and membrane currents were recorded by means of the
      whole cell configuration from guinea pig ventricular myocytes. RESULTS:
      Resembling the effects of CTL derived lytic granules, perforin caused gradual
      myocyte shortening and contracture, leading to complete loss of the rod shaped
      morphology and to cell destruction. These changes were preceded by shortening of
      action potential duration and reduction of resting potential and action potential
      amplitude, followed by complete inexcitability. Granzyme A alone was ineffective,
      but accelerated the deleterious effects of perforin on the morphological and
      electrophysiological properties of myocytes. The effects of perforin were further
      evaluated by measuring membrane currents by means of the whole cell voltage
      clamp. Perforin induced discrete changes in membrane current, reminiscent of
      single ion channels, with large conductance and open time of up to several
      seconds. Linear regression analysis of the channel I-V relations resulted in a
      conductance of 890 pS and a reversal potential of -7.6 mV. These results suggest
      that perforin induces large non-selective channels, which can account for most of
      the observed adverse effects. CONCLUSIONS: As CTL participate in the
      immunological rejection of the transplanted heart, it is conceivable, but remains
      to be shown, that part of this damage is inflicted by perforin containing lytic
      granules.

PMID- 7517792
TI  - Influence of arterial diameter on vasomotor responses in the porcine coronary
      vasculature.
AB  - OBJECTIVE: The aim was to determine whether regional differences in arterial
      responses to vasoconstrictor and vasorelaxant agonists exist within the minipig
      coronary vasculature. METHODS: Hearts were obtained from miniature pigs (20-40
      kg) immediately after death. First and third order arterial branches of the left
      anterior descending artery were dissected from within the subepicardium and
      mounted as ring preparations in a small vessel myograph for measurement of
      isometric tension under standardised conditions. Contractile responses to
      acetylcholine, noradrenaline, and U46619, and the relaxation responses to
      noradrenaline, bradykinin, and substance P were measured. Arterial tone was
      increased with KCl or acetylcholine prior to addition of vasodilator agonists.
      RESULTS: First order branches were more sensitive to the constrictor influence of
      acetylcholine than third order branches [pD2 values 6.42(SEM 0.07), n = 13, and
      6.26(0.07), n = 13, for first and third order respectively, p < 0.05]. U46619 did
      not induce contractile responses in arteries less than 210 microns in diameter.
      Noradrenaline only induced small contractile responses in the presence of
      propranolol following removal of the endothelium. In arteries preconstricted with
      40 mM KCl, noradrenaline induced relaxation which was inhibited by propranolol
      and was uninfluenced by arterial calibre. In the presence of propranolol,
      noradrenaline-mediated relaxations of acetylcholine-preconstricted arteries were
      endothelium dependent and alpha 2 adrenoceptor mediated, and greater in first
      order than in third order branches [58(5)%, n = 9, and 26(8)%, n = 9, for first
      and third order branches respectively, p < 0.05]. Relaxations mediated by
      bradykinin and substance P were not influenced significantly by arterial calibre
      but were greater in arteries preconstricted with acetylcholine than with KCl.
      CONCLUSIONS: In isolated minipig coronary arteries the vasoconstrictor responses
      to acetylcholine and U46619, and the endothelium dependent, noradrenaline
      mediated relaxations, differ according to the branching order studied. These data
      provide further evidence for a regional heterogeneity of vascular responses in
      the porcine coronary vasculature.

PMID- 7517793
TI  - Antibodies to murine CD40 protect normal and malignant B cells from induced
      growth arrest.
AB  - We have previously described the production of polyclonal anti-murine CD40
      antibodies that specifically bind recombinant murine CD40 expressed on L cells
      and induce vigorous proliferation of normal murine B lymphocytes. The current
      study utilizes these antibodies to explore the distribution and function of CD40
      in murine B cell development. Murine CD40 is expressed at high levels by normal
      splenic B cells and all Ig-positive B cell lymphomas tested to date. It is not
      expressed by the 70Z/3 pre-B cell line, BaF3 pre-B cell line, or by numerous T
      cell and myeloid cell lines. 70Z/3 pre-B cells can be induced to express CD40 by
      LPS stimulation of the cells. Stimulation of purified splenic B cells with anti
      CD40 antibodies causes upregulation of class II MHC antigens, CD23, and ICAM-1
      and results in extensive aggregation of the cells. Antibodies to murine CD40 are
      extremely effective at rescuing malignant and normal B cells from induced growth
      arrest. Anti-CD40 antibodies protect WEHI-231 and CH31 B lymphoma cells from
      growth arrest induced by soluble anti-IgM antibodies, TGF beta, or a combination
      of both stimulants. Similarly, anti-IgM preactivated normal splenic B cells which
      normally die rapidly from growth arrest after 1 or 2 days culture produce a
      vigorous proliferative response to subsequent stimulation with anti-CD40
      antibodies plus IL-4. Interestingly, anti-CD40 antibodies provide little to no
      protection against B lymphoma growth arrest induced by immobilized anti-IgM
      antibodies. These data confirm and extend functional properties assigned
      previously to human CD40 and identify numerous defined murine model systems to
      explore the molecular basis of CD40-mediated protection from induced B cell
      growth arrest.

PMID- 7517795
TI  - Repertoire of rat MBP-reactive T cells: DNA sequencing analysis further
      demonstrates the clonal heterogeneity of rat T cells reactive against
      encephalitogenic epitopes.
AB  - Reports of the expression of very similar TCR structures by disparate rodent
      encephalitogenic T cells reactive with regions of MBP have aroused much interest
      for both theoretical and practical reasons. To ascertain the extent to which
      structural requirements of epitope recognition constrain TCR expression by MBP
      reactive T cells, we set out to estimate the size of the overall repertoire of
      TCR beta-chain V beta-D beta-J beta (VDJ) assemblies in T cells of Lewis rats
      specific for MBP(68-88) as well as those specific for MBP(87-99). We previously
      reported that such T cells can express a diversity of V beta genes as revealed by
      PCR analysis. In this study, we have used direct sequencing of PCR products
      amplified from encephalitogenic T-cell clones and pauciclonal T-cell lines to
      demonstrate that VDJ structures of the rat T cells specific for either residues
      68 to 88 or 87 to 99 of MBP are highly heterogeneous. Our results showed that (1)
      no pattern is evident in the utilization of germline J gene segments by
      individual T-cell clones; from a total of over 100 successfully sequenced clones
      displaying in-frame rearrangements, all the J beta segments have been
      demonstrated. (2) Even among the T-cell clones which share the V beta expression,
      J beta is variable. (3) Due to joining variations between the V beta, D beta, and
      J beta gene segments, no two of the T-cell clones examined share entire VDJ
      structures. Our study is the first report of nucleotide and amino acid sequences
      of TCR beta-chains from rat encephalitogenic T cells expressing V beta genes
      other than V beta 8.2. It demonstrates that the TCR repertoire of the MBP
      reactive as well as encephalitogenic T cells is heterogeneous, even though a
      certain T-cell subset frequently dominated by the mechanism needs to be
      clarified.

PMID- 7517794
TI  - An HIV p24 heptapeptide down-regulates antigen-specific responses in vitro
      interfering at the level of the T3-Ti complex.
AB  - Ch7 (RGSDIAG), a synthetic heptapeptide derived from a conserved region of HIV
      p24 (aa 232-238), was previously shown to suppress antigen-induced responses in
      cultures of normal human peripheral blood lymphocytes (PBL). We show in this
      paper that Ch7 is the shortest peptide retaining full inhibitory capacity.
      Further, the peptide inhibited efficiently and in a dose-dependent manner the
      induction of a specific antibody response to the antigens SRC (sheep red cells)
      and Candida albicans but did not exert any effect on the induction of
      immunoglobulin-secreting cells in PWM-stimulated cultures. Finally, Ch7 inhibited
      anti-CD3-induced lymphoproliferation but did not affect anti-CD2 activation.
      These results suggest that a conserved epitope of HIV p24 may be able to prevent
      the induction of antigen-specific antibody responses by interfering with
      lymphocyte activation via the T3-Ti complex, resulting in the abrogation of
      immune functions that are defective in HIV-infected individuals.

PMID- 7517796
TI  - Inhibition of human B lymphocyte cell cycle progression and differentiation by
      rapamycin.
AB  - In this study, we have analyzed the effects of the immunosuppressive agent
      rapamycin on the activation of highly purified normal human B lymphocytes. When
      the polyclonal activators Staphylococcus aureus (SA) and soluble CD40 ligand
      (CD40L) were used to stimulate B cells, rapamycin inhibited both interleukin 2
      (IL2)-dependent and -independent proliferation, as well as IL2-dependent
      differentiation into antibody-secreting cells. Cell cycle analysis indicated that
      rapamycin inhibited the progression of SA+IL2-stimulated B cells past the mid-G1
      phase of the cell cycle. To begin to identify rapamycin-sensitive signaling
      events essential for B cell activation, we examined the effects of rapamycin on
      p34cdc2 and p33cdk2 kinase activities. SA+IL2 stimulation induced the activation
      of both cyclin-dependent kinases. Of interest, rapamycin abrogated the activation
      of both p34cdc2 and p33cdk2. Our results indicate therefore that rapamycin
      inhibits a number of SA- and CD40L-inducible events that may be necessary for
      both entry into S phase and for permitting subsequent B cell differentiation.
      These studies emphasize the utility of this drug as a tool to begin to dissect
      the activation pathways utilized by human B cells, as well as to provide
      implications for the therapeutic use of rapamycin in vivo.

PMID- 7517797
TI  - [The palliative treatment of hepatocarcinoma: chemoembolization vs. the
      combination of tamoxifen plus beta-interferon].
AB  - Clinical and experimental data show that beta-IFN enhances the effect of
      tamoxifen on advanced breast cancer. There is a similarity between breast and
      liver as far as the proliferating effect on normal and neoplastic tissue of
      estrogen and progestin receptors is concerned. The authors tested this
      pharmacological association in unresectable liver neoplasms. They considered 76
      (not randomized) patients affected with HCC; 38 were treated by trans-arterial
      chemoembolization (TACE) and 38 to beta-INF and tamoxifen (the 2 groups were
      comparable according to age, sex, Child-Pugh score, Okuda and TNM stages,
      cirrhosis etiology). The treatment response (positive when a tumor diameter
      decreased or stabilization was observed) was similar in the two groups; in the
      TACE group, the presence of a peritumoral capsula had a significant influence on
      survival (p < 0.02); on the other hand, in the patients treated with beta-INF and
      tamoxifen important factors for a better prognosis were the TNM stage (I and II,
      p < 0.02) and a symptom-free condition (p < 0.04). The authors believe the beta
      INF and tamoxifen treatment could represent an effective alternative in the
      management of unresectable HCC. A better knowledge of the presence and meaning of
      estrogen and progestin receptors in the neoplastic tissue may allow a better
      selection of patients.

PMID- 7517798
TI  - Induction of nitric oxide synthase gene by interleukin-1 beta in cultured rat
      cardiocytes.
AB  - BACKGROUND: Impaired myocardial contractility in septic shock is protracting,
      which may be caused by cytokine-induced nitric oxide (NO) synthesis in the heart.
      However, the cellular mechanism by which cytokines induce nitric oxide synthase
      (NOS) in cardiocytes remains obscure. METHODS AND RESULTS: We studied the effect
      of human recombinant interleukin-1 beta (IL-1 beta) on synthesis of NO2-/NO3-
      (NOx) and the expression of NOS mRNA and protein in cultured neonatal rat
      cardiocytes. IL-1 beta dose-dependently (0.1 to 10 ng/mL) stimulated NOx
      production as a function of time (6 to 48 hours). Northern blot analysis using
      complementary DNAs for rat brain-type constitutive (c) NOS and mouse macrophage
      type inducible (i) NOS as probes showed that IL-1 beta induced expression of mRNA
      for iNOS but not for cNOS, starting after 6 hours and reaching a maximum after 48
      hours in cardiocytes. IL-1 beta similarly induced iNOS mRNA expression in
      cultured adult rat cardiocytes in a time-dependent manner. Western blot analysis
      using specific antibody against the N-terminal fragment of mouse iNOS revealed
      the expression of 130-kD iNOS-like protein in IL-1 beta-treated cardiocytes.
      Northern blotting and immunocytochemical study revealed that IL-1 beta-induced
      iNOS mRNA and iNOS-like immunoreactivity were exclusively localized to cardiac
      myocytes but also to nonmyocytes, to a lesser extent. NG-mono-methyl-L-arginine,
      an NOS inhibitor, completely blocked the IL-1 beta-induced NOx production, whose
      effect was reversed by L-arginine but not by D-arginine. Dexamethasone inhibited
      the IL-1 beta-induced NOx production as well as iNOS mRNA expression.
      Cycloheximide and actinomycin D completely inhibited the IL-1 beta-induced NOx
      production and iNOS mRNA expression. Neither a calmodulin inhibitor (W-7), a
      protein kinase C inhibitor (calphostin C), nor a Ca2+ channel antagonist
      (nicardipine) showed any effect on the IL-1 beta-induced NOx production.
      CONCLUSIONS: These data demonstrate that IL-1 beta induces macrophage-type iNOS
      mRNA expression mainly by cardiac myocytes but also by nonmyocytes to a lesser
      extent, and subsequent de novo protein synthesis of iNOS leads to excessive local
      production of NO by cardiocytes.

PMID- 7517799
TI  - Potential importance of tissue angiotensin-converting enzyme inhibition in
      preventing neointima formation.
AB  - BACKGROUND: Angiotensin II (Ang II) induces vascular smooth muscle cell migration
      and growth in vitro and induces DNA synthesis in vascular smooth muscle in vivo.
      Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor
      antagonists inhibit neointimal hyperplasia in many experimental models of
      restenosis. However, recent clinical trials (MERCATOR and MARCATOR) reported that
      treatment with low (antihypertensive) doses of an ACE inhibitor (cilazapril)
      failed to prevent restenosis. Because ACE activity is induced in the neointima
      after injury, we hypothesize that the inhibition of neointimal development may be
      dependent on the suppression of tissue ACE activity, which in turn is dependent
      on the dose of the ACE inhibitor. METHODS AND RESULTS: To test this hypothesis,
      we treated rats with increasing doses of an ACE inhibitor, quinapril, before
      injury of the carotid artery. Blood pressure, serum and tissue ACE activity, and
      neointimal area were measured. The results demonstrated a dose-dependent
      inhibition by quinapril of serum and tissue ACE activities and neointima
      formation. However, the IC50s for blood pressure reduction and serum ACE
      inhibition were significantly lower than that observed for the suppression of
      neointima formation. The degree of neointimal formation showed a better
      correlation with residual tissue ACE than with serum ACE or blood pressure.
      CONCLUSIONS: These results demonstrate a dissociation of the ability of an ACE
      inhibitor to decrease blood pressure and inhibit circulating ACE activity from
      its ability to inhibit tissue ACE activity. These results suggest that the need
      for a higher dose of an ACE inhibitor for the inhibition of neointima formation
      may be due to the relative difficulty in inhibiting tissue ACE activity.

PMID- 7517801
TI  - Characterization and development of glial and other non-neuronal cells in chick
      Edinger Westphal cultures.
AB  - Cultures of dissociated Edinger Westphal nuclei, dissected from embryonic chick
      brainstems, were screened immunohistochemically for a variety of non-neuronal
      cell markers. In young cultures, small clusters of cells were stained by the
      oligodendrocyte-specific antibodies 04 and 01. In older cultures, larger groups
      of cells were 04 and 01 positive, sheets of myelin-like membrane were elaborated,
      and immunoreactivity for proteolipid protein appeared. This sequence resembles
      that observed in well-characterized rodent brain cultures and suggests that
      oligodendrocytes in chick Edinger Westphal cultures differentiate in a pattern
      similar to rodent oligodendrocytes in culture. Variable numbers of cells were
      immunoreactive for glial fibrillary acidic protein. Many vimentin positive cells
      were observed, some of which morphologically resembled flat astrocytes. Together
      with the widespread presence of vimentin, large patches of fibronectin-like
      immunoreactivity suggested the presence of fibroblasts and/or endothelial cells.
      An anti-thymocyte polyclonal antibody stained a subset of cobblestone-shaped
      cells, possibly endothelial cells, in both Edinger Westphal cultures and control
      cultures of skin fibroblasts. Staining for smooth muscle myosin was detected in
      several patches of cells, tentatively identifying them as pericytes or smooth
      muscle cells. In conclusion, Edinger Westphal cultures contain a diverse and
      varying population of non-neuronal cells loosely organized in large, overlapping
      islands of cell types and including oligodendrocytes, astrocytes, possibly
      fibroblasts, endothelial cells, pericytes and/or smooth muscle cells.

PMID- 7517800
TI  - Developmental changes in modulation of calcium currents of rabbit ventricular
      cells by phosphodiesterase inhibitors.
AB  - BACKGROUND: We have previously shown major differences in beta-adrenergic and
      muscarinic modulation of L-type calcium currents (ICa) in newborn and adult
      rabbit heart. However, little is known about developmental changes in modulation
      of ICa by phosphodiesterases (PDEs), which also regulate intracellular cAMP
      concentration by its hydrolysis. METHODS AND RESULTS: Enzymatically isolated
      adult and newborn (1- to 3-day-old) rabbit ventricular myocytes were used to
      study the effects of PDE inhibitors on ICa measured by the whole-cell patch-clamp
      method. 3-Isobutyl-1-methyl-xanthine (IBMX), a nonselective PDE inhibitor,
      increased ICa in a dose-dependent manner for both groups. The maximal effect of
      IBMX, expressed as percentage increase in ICa over control levels, was greater
      for newborn myocytes than for adult myocytes, but the effects of IBMX applied
      alone were observed only at concentrations > 10 mumol/L. The concomitant use of
      0.1 mumol/L isoproterenol produced a significant potentiation of the IBMX effect
      on ICa, with a significant additive effect of IBMX in newborn myocytes even at
      0.05 mumol/L IBMX. The concomitant use of a subthreshold concentration of IBMX
      (0.1 mumol/L) did not potentiate the dose dependence of adult ICa on
      isoproterenol but did markedly potentiate the dose dependence of newborn ICa on
      isoproterenol. The Emax and EC50 of isoproterenol in the presence of 0.1 mumol/L
      IBMX on newborn ICa were 235% and 8 nmol/L, respectively, whereas the Emax and
      EC50 of isoproterenol in the absence of IBMX on newborn ICa were 111% and 81
      nmol/L, respectively. The addition of 50 mumol/L IBMX to 10 mumol/L isoproterenol
      markedly increased the newborn ICa density up to a level equivalent to that
      reached with 200 mumol/L cAMP in the pipette (14.9 +/- 1.2 versus 13.4 +/- 0.7
      pA/pF). Our data suggest that the inhibition constant (Ki) of IBMX for inhibiting
      PDEs that participate in the regulation of ICa is much lower in newborn than in
      adult myocytes. Milrinone 1 mumol/L, a selective PDE III inhibitor, increased the
      0.1 mumol/L isoproterenol-stimulated ICa of adult myocytes but had no significant
      additive effect for the 0.1 mumol/L isoproterenol-stimulated ICa of newborn
      myocytes. Rolipram 1 mumol/L, a selective PDE IV inhibitor, increased the 0.1
      mumol/L isoproterenol-stimulated ICa for newborn myocytes but had no significant
      additive effect for the 0.1 mumol/L isoproterenol-stimulated ICa for adult
      myocytes. CONCLUSIONS: These results suggest that the most important PDE isozyme
      for regulation of ICa of rabbit myocytes changes from PDE IV to PDE III during
      the postnatal period.

PMID- 7517803
TI  - Private practice and public research: the patients of R. T. H. Laennec.

PMID- 7517804
TI  - The development of medical specialization in nineteenth-century Paris.

PMID- 7517802
TI  - Developmental expression of N-CAM epitopes in the rat spinal cord during
      corticospinal tract axon outgrowth and target innervation.
AB  - The neural cell adhesion molecule (N-CAM) is an integral membrane glycoprotein
      which mediates the adhesion of neurons to neurons and to other types of cells.
      During development, the N-CAM molecule is converted from a microheterogenous,
      highly sialylated, embryonic form (200-230 kDa) to several distinct, less
      sialylated but more adhesive, adult forms (120, 140 and 180 kDa). Monoclonal
      antibodies to epitopes of N-CAM (designated 5A5, 12F8, 5B8, 12F11 and 14E6) were
      used to investigate the spatial and temporal distribution of these neural cell
      adhesion molecules during the development of the corticospinal tract (CST) in rat
      spinal cord, from postnatal day 1 (P1) until adulthood. The light microscopical
      observations indicate that the embryonic form of N-CAM (200-230 kDa) recognized
      by 5A5 and 12F8 antibodies, respectively, is probably involved in the process of
      initial ingrowth of pioneer CST-fibers into the ventralmost part of the dorsal
      funiculus. The adult forms of N-CAM (120, 140, 180 kDa) recognized by 5B8, 12F11,
      and 14E6 antibodies, respectively, are present during later stages of CST white
      matter ingrowth and probably involved in fasciculation of the later arriving CST
      axons. During the period of CST target innervation (P4-P21), a gradual shift from
      embryonic (200-230 kDa) to adult (120, 140 and 180 kDa) forms of N-CAM occurs in
      spinal white matter and in the spinal gray matter adjacent to the ventral most
      part of the dorsal funiculus. The presence of embryonic N-CAM (200 kDa), with its
      low adhesive capacity in the CST outgrowth area may allow the CST axons to
      branch. If this branching is no longer desirable, only the higher affinity forms
      of N-CAM (120, 140 and 180 kDa) are expressed. The absence of N-CAM on CST target
      interneurons in the base of the dorsal horn and intermediate spinal gray matter
      strongly suggest that N-CAM is not involved in CST synapse formation. Together,
      these results suggest that various forms of N-CAM are involved in CST spinal
      white matter tract formation and subsequent target innervation, but not in the
      process of synapse formation.

PMID- 7517807
TI  - From religious to bio-medical anti-semitism: the career of Jules Soury.

PMID- 7517806
TI  - The uses of male hysteria: medical and literary discourse in nineteenth-century
      France.

PMID- 7517805
TI  - Doctors and families in France, 1880-1930: the cultural reconstruction of
      medicine.

PMID- 7517808
TI  - Academic medicine and medical industrialism: the regulation of secret remedies in
      nineteenth-century France.

PMID- 7517809
TI  - Vicq d'Azyr, anatomy and a vision of medicine.

PMID- 7517810
TI  - Medical microscopy in Paris, 1830-1855.

PMID- 7517811
TI  - Bacteriological research and medical practice in and out of the Pastorian school.

PMID- 7517812
TI  - La Visite: Mary Putnam Jacobi and the Paris Medical Clinics.

PMID- 7517813
TI  - Consultation by letter in early eighteenth-century Paris: the medical practice of
      Etienne-Francois Geoffroy.

PMID- 7517814
TI  - Cytokine control of nutrition and metabolism in critical illness.
AB  - During the last two decades, major advances in technology and in our fundamental
      understanding of the biologic aspects of sepsis and cancer cachexia have
      dramatically affected the therapeutic strategies available to the surgeon to care
      for critically ill patients. It is clear, however, that cytokines affect whole
      body nutrition and metabolism and are responsible for many of the clinically
      observed nutritional effects of injury, infection, and cancer, including fever,
      hypermetabolism, anorexia, protein catabolism, cachexia, and altered fat,
      glucose, and trace mineral metabolism. These metabolic and nutritional effects of
      cytokines are influenced by the nutritional status of the host, which is
      generally altered during the course of the critical illness. In the future, the
      use of specialized diets and the use of selective cytokine blockade are likely to
      be important components of the overall care of the catabolic patient.

PMID- 7517815
TI  - Practical aspects of fixatives in high resolution nuclear image analysis.
AB  - Three different methods of fixation (ethanol/Carbowax, formaldehyde, and Carnoy)
      and four different protocols (without Bohm post-fixation on an uncoated slide,
      and with Bohm post-fixation on Poly-L-Lysine coated slide, an uncoated slide and
      a previously Papanicolaou stained slide) were evaluated for their application in
      high resolution image analysis of Feulgen stained nuclei. The aim of the study
      was to find a combination with the best reproducibility and the least variance
      under normal laboratory conditions. Care was taken not to exclude any "normal"
      laboratory variability. The combinations were evaluated for densitometric,
      geometric, as well as texture features. Selected features were determined on a
      CAS-100 using the Cell Measurement Program (Cell Analysis Systems, Inc. Lombard,
      IL). Diploid and tetraploid rat liver nuclei were used. Ethanol/Carbowax fixation
      with Bohm post-fixation proved most stable. This fixation method also gave
      feature values for previously Papanicolaou stained slides that were comparable to
      direct Feulgen stained nuclei. Acceptable results were achieved with all three
      fixatives and the various combinations if one adhered strictly to protocol. In
      routine practice this usually does not happen. Therefore Ethanol/Carbowax
      fixation with Bohm post-fixation was considered most suited for routine
      determination of feature values on the CAS-100.

PMID- 7517818
TI  - Enteroglucagon. A putative humoral factor inducing pancreatic hyperplasia after
      proximal small bowel resection.
AB  - The present study evaluated pancreatotrophic factors after massive small bowel
      resection. Specifically, we examined the role of enteroglucagon in compensatory
      pancreatic hyperplasia after proximal small bowel resection (PSBR) by using rats
      fed a fiber-free elemental diet or an elemental diet containing pectin. PSBR
      increased the net pancreatic weight as well as the protein, DNA, RNA, and amylase
      contents, and elevated plasma enteroglucagon levels. Pectin addition to the diet
      provoked a further increase in these parameters and significant positive
      correlations were found between the plasma enteroglucagon levels and the protein,
      DNA, and RNA contents of the pancreas. Plasma gastrin and CCK levels were not
      affected by the small bowel resection. These results indicate that enteroglucagon
      may exert a potent trophic effect on the pancreas after PSBR.

PMID- 7517816
TI  - Immunofluorescent quantification of tyrosine phosphorylation of cellular proteins
      in whole cells by flow cytometry.
AB  - Tyrosine phosphorylation of proteins, a major event in the transduction of
      mitogenic signals, was analysed by flow cytometry with a fluorescent
      antiphosphotyrosine monoclonal antibody, on formaldehyde-fixed, permeabilized
      cells. We have used this method (PY-Facs) to study activation of normal human T
      lymphocytes and cells of a leukemic T-cell line: Jurkat. In contrast to normal T
      cells, Jurkat cells as well as three other leukemic cell lines display a higher
      constitutive level of tyrosine phosphorylation. This level of tyrosine
      phosphorylation results from an equilibrium that can be up-regulated by the
      tyrosine phosphatase inhibitor, vanadate peroxide, and down-regulated by the
      tyrosine kinase inhibitors, genistein and staurosporine. We have also observed an
      increased tyrosine phosphorylation of proteins after mitogenic stimulation of
      Jurkat cells via T-cell receptor triggering. In addition, the entry of normal
      purified T cells from G0 phase into the cell cycle after co-stimulation with a
      phorbol ester and an anti-receptor antibody is correlated with a pronounced
      increase in tyrosine phosphorylation. We thus confirmed that this biochemical
      event was tightly associated with the activation status of the cells. The
      rapidity and sensitivity of the method we describe here make it particularly
      convenient for routine use and processing of a large number of samples, e.g.,
      during analysis of human tumors. Moreover, because it retains sufficiently the
      integrity of treated cells and does not alter expression of membrane antigens,
      this method is suitable for multiparametric analysis, particularly for
      simultaneous studies associating the measure of tyrosine phosphorylation levels
      with possible modifications of membrane or intracellular structures as well as
      with cell cycle status.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517817
TI  - Helicobacter pylori potentiates histamine release from rat serosal mast cells
      induced by bile acids.
AB  - In the present study we have experimentally addressed the effects of Helicobacter
      pylori on the bile acid capability of histamine release. Bile acids alone were
      confirmed to be able to induce in vitro histamine release from rat serosal and
      mucosal mast cells. On the contrary, no significant histamine release was
      obtained when incubating any Helicobacter pylori preparations alone with mast
      cells. However, histamine release induced by bile acids was significantly
      enhanced, without any significant increase in lactate dehydrogenase activity,
      when whole washed or formalin-killed bacterial cells or crude cell walls were
      incubated with mast cells in the presence of cholic (0.3 mM), deoxycholic (0.3
      mM), or lithocholic (0.3 mM) acids, chenodeoxycholylglycine (0.3 mM), and
      deoxycholyltaurine (3 mM). The electron microscopic features of mast cells
      incubated with Helicobacter pylori were consistent with an exocytotic secretion.
      The release of histamine induced by 0.3 mM deoxycholic acid in the presence of
      Helicobacter pylori was inhibited by the preincubation of the cells with dimaprit
      (an H2 agonist) and potentiated by the H2 antagonist, ranitidine. The current
      results suggest a link between human Helicobacter pylori infection and histamine
      release and a possible involvement of gastric mucosal mast cells in the
      pathogenesis of Helicobacter pylori-associated gastritis.

PMID- 7517819
TI  - Helicobacter pylori activates gastric mucosal mast cells.

PMID- 7517821
TI  - Tramadol analgesia: synergy in research and therapy. Proceedings of a satellite
      symposium associated with the 7th World Congress on Pain. Paris, France, 24
      August 1993.

PMID- 7517820
TI  - Tramadol analgesia. Synergy in research and therapy.

PMID- 7517822
TI  - Tramadol for the management of acute pain.
AB  - This paper reviews the use of tramadol in the management of acute pain. Tramadol
      is a weak opioid analgesic with a potency comparable to that of pethidine. While
      it is not recommended as a supplement to general anaesthesia because of its
      insufficient sedative activity, tramadol has been successful in the treatment of
      postoperative pain. Several studies have demonstrated its analgesic efficacy
      after intramuscular and intravenous application, both in adults and children.
      Moreover, negligible respiratory depressant activity and only minor side effects
      have consistently been shown. Patient-controlled analgesia with tramadol has been
      frequently employed and was well accepted by the patients. There have been only a
      few studies of oral or spinal application of tramadol in acute pain states.
      Tramadol has also been used for the control of pain associated with labour and
      acute myocardial infarction, as well as for the management of trauma pain. In
      summary, tramadol can be recommended as a basic analgesic for the treatment of
      patients with moderate to severe pain.

PMID- 7517823
TI  - The pharmacology of tramadol.
AB  - (+/-)-Tramadol is a central analgesic with low affinity for opioid receptors. The
      rate of production of its M1 metabolite (O-demethyl tramadol) is influenced by
      debrisoquine-type polymorphism, and this metabolite shows a higher affinity for
      opioid receptors than the parent drug. Experimental and clinical data suggest
      that tramadol may also exert its analgesic effect through direct modulation of
      central monaminergic pathways. Indeed, after a single oral dose, the role of the
      mu-receptor agonist component of the antinociceptive effect of tramadol appears
      to be minor, with most of the analgesic effect being attributable to nonopioid
      properties of the parent compound. Approximately 2-fold accumulation of the
      parent compound and the M1 metabolite may be expected during multiple dose
      treatment. The duration of analgesic effect after a single oral dose of tramadol
      100 mg is about 6 hours. Clinical experience has confirmed that tramadol is an
      effective and relatively safe analgesic that may be of value in several pain
      conditions not requiring treatment with strong opioids.

PMID- 7517825
TI  - Acute effects of tramadol in methadone-maintained volunteers.
AB  - The opioid agonist and antagonist properties of tramadol were assessed in 6 male
      opioid-dependent volunteers enrolled in a methadone maintenance programme.
      Subjects participated in 3 experimental sessions in which the effects of
      intramuscular tramadol 100 and 300 mg and placebo were evaluated. Tramadol
      neither produced morphine-like effects nor precipitated a withdrawal syndrome;
      its subjective, behavioural and physiological effects were not different from
      those of placebo. Although the results of this study suggest that tramadol has a
      low abuse liability in opioid-dependent subjects, higher doses should be tested
      to confirm these data.

PMID- 7517824
TI  - Chronic pain--challenge and response.
AB  - Tramadol is effective in treating both acute and chronic pain, exhibiting a
      potency equivalent to that of pethidine, and it has an acceptable adverse event
      profile. Whilst the most common adverse events are nausea, vomiting, drowsiness
      and dizziness, as would be expected from an opioid, there is a noticeable lack of
      respiratory depression. This latter property, together with its low potential for
      the development of tolerance and dependence, make tramadol a most interesting
      agent for clinical use. The studies reported in this article illustrate the
      beneficial and adverse effects of tramadol to enable the clinician to judge the
      value of this agent.

PMID- 7517828
TI  - Treatment of lipoprotein disorders in women. Proceedings of a workshop.
      Frankfurt, October 8-9, 1993.

PMID- 7517826
TI  - New clinical experience with tramadol.
AB  - The analgesic efficacy of tramadol has been recently reassessed as part of a new
      clinical development programme to support an application for registration in the
      USA. This article reviews the results of single dose and short term studies of
      oral tramadol 50, 75, 100 and 150 mg in various acute pain conditions. In a
      double-blind single dose study conducted in 161 patients with severe pain
      following caesarean section, tramadol 75 and 150 mg and the combination of
      paracetamol 650 mg with dextropropoxyphene napsylate 100 mg were shown to be
      effective and statistically superior to placebo. The results from this and 17
      other similar studies in patients with pain after surgery (n = 1594) or dental
      extraction (n = 1859) including other comparators were included in a pooled
      analysis. Tramadol 100 mg was the optimal single dose for acute pain and tramadol
      50 mg showed similar analgesic efficacy to codeine 60 mg. Multiple dose short
      term studies (n = 520) with tramadol 50, 75 and 100 mg demonstrated a
      statistically significant and dose-dependent reduction in the consumption of
      either ibuprofen or morphine as escape medication. New pharmacokinetic data show
      that steady-state plasma tramadol concentrations reached after oral
      administration of 50 mg doses every 6 hours are similar to those obtained after
      administration of a 100 mg single oral dose (250 micrograms/L). This rationale is
      supported by the results of long term studies in which the average daily dose of
      tramadol was approximately 250 mg.

PMID- 7517827
TI  - Lipoprotein metabolism. An overview.
AB  - The biological benefits of lipids as sources of energy and precursors of cell
      components have led to the evolution of a complex plasma lipoprotein transport
      system, through which gram quantities of cholesterol, triglyceride, and
      phospholipid pass each day. A wide variety of tissues make demands on this pool.
      The adrenal glands and gonads avidly assimilate lipoprotein cholesterol for the
      production of steroid hormones, and rapidly dividing intestinal villus cells take
      up the sterol for membrane synthesis. Metabolically active tissues such as
      skeletal muscle use plasma triglyceride for energy production, while in times of
      surfeit this lipid is directed into adipocytes for storage. Two organs, the liver
      and intestine, play a particularly important role in corporeal lipid metabolism,
      and together are responsible for the majority of lipoprotein synthesis and
      catabolism. In the plasma, lipid transport is regulated by specific
      apolipoproteins (apo), lipoprotein receptors, lipolytic enzymes and transfer
      proteins, which act in concert to maintain the balance of cholesterol and
      triglyceride homeostasis in tissues and plasma; their malfunction may cause or
      contribute to the development of dyslipidaemia.

PMID- 7517829
TI  - Analysis of angiographic trial data in women.
AB  - There are few angiographic trials of cholesterol lowering in women. Two trials
      have included a sufficient number of women for meaningful assessment of lesion
      change, as determined by quantitative coronary angiography. In the University of
      California, San Francisco Specialized Center of Research in Arteriosclerosis
      (UCSF SCOR) trial, 72 patients (57% women) with familial hypercholesterolaemia
      (90% of whom had no overt coronary heart disease) were randomised to receive
      either diet and intensive drug therapy (combinations of colestipol, nicotinic
      acid and lovastatin) or diet and modest doses of colestipol, according to
      baseline low density lipoprotein cholesterol level. Coronary angiograms were
      obtained at 2-year intervals. Change in percentage area of stenosis (the primary
      end-point) in women receiving intensive drug treatment was -2.06% compared with
      +1.07% for the controls (p = 0.05). For the intensively treated men,
      corresponding values were -0.88% compared with +0.41% for the controls
      (difference not significant). In a recently completed trial in Canada, 269 men
      and 62 women with established coronary heart disease were randomised to receive
      either diet alone, or diet and lovastatin (up to 80 mg daily). In men, the
      increase in percentage diameter of stenosis was reduced by 43% (p = 0.05), and in
      women by 40% (not significant). By contrast, new lesions appeared in 4% of women
      assigned to intensive drug treatment, compared with 45% of those randomised to
      diet (p < 0.001). In men, new lesions appeared in 18% and 29% of patients,
      respectively (p = 0.047). These data suggest that coronary artery lesions in
      women respond at least as well as those in men to cholesterol lowering.

PMID- 7517831
TI  - Postmenopausal hormone replacement therapy, coronary heart disease and plasma
      lipoproteins.
AB  - This review outlines the changes in serum lipoprotein (Lp) concentrations at the
      menopause. The effect of hormone replacement therapy with estrogen and a variety
      of progestogens is illustrated by a number of recent studies. Analysis of the
      effects of estrogen replacement in the primary prevention of coronary heart
      disease (CHD) is discussed. During the last 4 years, there have been 4
      observational studies of the use of estrogen in postmenopausal women with CHD as
      assessed by coronary angiography. In all of these studies, estrogen has been
      associated with a reduction in CHD, most strikingly in a study of survival over
      10 years. However, there is an overwhelming need for a randomised controlled
      trial of estrogen for secondary prevention. The role of estrogen in the treatment
      of type II hyperlipoproteinaemia has been recognised, and a study describing its
      effect is discussed. Again, there is need for data from well controlled clinical
      trials to clearly establish the benefits of estrogen therapy. A further aspect
      for investigation is a study of the non-lipoprotein-mediated effects of estrogen,
      particularly those on vasomotion. Finally, the intriguing effects of both
      androgenic and estrogenic steroids on Lp(a) are discussed.

PMID- 7517830
TI  - Postmenopausal hormone replacement therapy and cardiovascular risk reduction. A
      review.
AB  - Administration of unopposed postmenopausal estrogen therapy protects against
      coronary heart disease (CHD) in women. This is mediated, in part, through
      beneficial effects on lipid and lipoprotein metabolism. Fewer data are available
      with regard to CHD risk reduction when a progesterone is required in addition to
      estrogen. Administration of continuous, rather than cyclic, estrogen-progesterone
      therapy may maintain the beneficial effects of estrogen and yet protect against
      the increase in endometrial cancer observed with estrogen therapy alone. Clinical
      guidelines for hormone replacement therapy await the completion of adequate
      controlled clinical trials.

PMID- 7517832
TI  - Hormone replacement therapy and the cardiovascular system. Nonlipid effects.
AB  - Coronary heart disease (CHD) is the leading cause of death in women, and the risk
      of this disease rises markedly after loss of ovarian function. Hormone
      replacement therapy (HRT) can reduce the incidence of CHD in postmenopausal women
      by 50%. HRT causes changes in lipids and lipoproteins, but it is now clear that
      many other effects of gonadal steroid hormones have important influences on the
      cardiovascular system. These nonlipid effects include a variety of changes in
      other metabolic risk factors for CHD, as well as direct arterial effects. Insulin
      resistance and hyperinsulinaemia may be pivotal disturbances in the pathogenesis
      of CHD. Estradiol reverses the effects of menopause on glucose and insulin
      metabolism, resulting in an increase in pancreatic insulin secretion and a
      decrease in insulin resistance, although other types of estrogen may not do this.
      Androgenic progestogens may oppose this potentially beneficial effect on insulin
      resistance. Central obesity is linked with many CHD risk factors, and HRT
      reverses the increased fat distribution that results from loss of ovarian
      function at the menopause. HRT may also improve the balance between coagulation
      and fibrinolysis, resulting in a reduction in arterial thrombosis. Finally,
      estradiol acts directly on the arterial wall, modifying both endothelium
      dependent and calcium-dependent processes. These actions result in improved blood
      flow and reduced blood pressure and, importantly, have the potential to reduce
      myocardial ischaemia.

PMID- 7517833
TI  - Effects of estrogen treatment on arterial wall structure and function.
AB  - Premenopausal women are relatively protected against coronary heart disease (CHD)
      compared with men, but lose this advantage after surgical or natural menopause.
      Consequently, estrogens are believed to confer significant protection against
      coronary artery atherosclerosis (CAA). In addition, epidemiological studies have
      shown lower rates of CHD in postmenopausal users of estrogen replacement therapy
      than in women not taking hormone therapy. The cynomolgus monkey model (Macaca
      fascicularis) has proved valuable for gaining a better understanding of the
      effects of estrogen on coronary artery function and CAA. We have found that
      premenopausal cynomolgus monkeys have less CAA than male monkeys and surgically
      postmenopausal female monkeys, and that the hyperestrogenic state of pregnancy
      further inhibits CAA progression. Ovarian-deficient stressed females had more
      extensive CAA and impaired vascular function compared with unstressed monkeys,
      and estrogen-treated females (premenopausal or postmenopausal) had less CAA than
      untreated monkeys. The treatment effect in this model appears to be partially
      mediated by a decrease in low density lipoprotein uptake and/or degradation, and
      an improvement in coronary artery vascular function.

PMID- 7517834
TI  - Gender-related response to fluvastatin in patients with heterozygous familial
      hypercholesterolaemia.
AB  - Hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors are potent
      cholesterol reducing agents that have been successfully used for the treatment of
      heterozygous familial hypercholesterolaemia (FH). A recent investigation revealed
      that several constitutional and genetic factors significantly determined the
      response of plasma lipids and lipoproteins to the HMG CoA reductase inhibitor
      fluvastatin. Gender has been identified through multivariate analysis as a major
      determinant of the plasma high density lipoprotein (HDL) cholesterol response.
      The current analysis was undertaken to determine possible gender-related
      fluvastatin dose-response differences. The analysis revealed that for HDL
      cholesterol, gender-related differences reach statistical significance only at
      the highest fluvastatin dose of 40 mg/day (females 22.9%, males 12.9%, p < 0.01).
      In parallel, the change in low density lipoprotein (LDL) cholesterol: HDL
      cholesterol ratio, an indicator of ischaemic heart disease risk, was also found
      to be affected by gender (females -38.4%, males -32.2%, p < 0.01). For LDL
      cholesterol, no consistent gender-related differences were found. In conclusion,
      the response of plasma lipid levels to fluvastatin in heterozygote FH patients is
      significantly affected by gender, with females achieving a more marked overall
      response, as indicated by higher HDL cholesterol levels and a lower LDL
      cholesterol: HDL cholesterol ratio.

PMID- 7517836
TI  - Efficacy and safety of fluvastatin in women with primary hypercholesterolaemia.
AB  - Women with primary hypercholesterolaemia are often considered for lipid-lowering
      drug therapy at a later age than men. With regard to the prevention of
      cardiovascular morbidity, women can expect to receive the same benefits from
      lipid-lowering treatment as men. Thus, it is of interest to evaluate the
      efficacy, safety and tolerability of the new lipid-lowering agent fluvastatin in
      women. A retrospective analysis was made on the basis of data from controlled
      clinical trials in which 1815 patients were treated with fluvastatin at a daily
      dose of > or = 20 mg, and 783 patients received placebo. 782 of the fluvastatin
      treated patients (43.1%) and 315 patients on placebo (40.2%) were women. Within
      these groups, 577 patients (73.8%) treated with fluvastatin and 183 patients
      receiving placebo (78.4%) were at least 50 years of age. The effect of
      fluvastatin 40 mg/day on low density lipoprotein (LDL) and high density
      lipoprotein (HDL) cholesterol was more favourable in women than in men. In women,
      the change from baseline was -26.7% for LDL cholesterol and 5.3% for HDL
      cholesterol. In men, the equivalent changes from baseline were -23.8% and 4.0%,
      respectively. All changes from baseline were highly significant (p < 0.001).
      Fluvastatin lowered triglycerides to a similar extent in women and men (7.1% vs
      6.9%, respectively). More women than men experienced a confirmed increase in
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) when
      receiving fluvastatin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517835
TI  - Efficacy and safety of fluvastatin, a new HMG CoA reductase inhibitor, in elderly
      hypercholesterolaemic women.
AB  - This multicentre open 6-week study evaluated the efficacy, safety and
      tolerability of fluvastatin, the first fully synthetic 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG CoA) reductase inhibitor, in elderly women with type IIa
      hypercholesterolaemia. After a 4-week single-blind placebo period, 22 elderly
      women (mean age 68 +/- 5 years) with primary hypercholesterolaemia [low density
      lipoprotein (LDL) cholesterol > 160 mg/dl] were enrolled in the trial.
      Fluvastatin 40 mg was administered once in the evening. At baseline, and after 3
      and 6 weeks of treatment, total cholesterol, LDL cholesterol, high density
      lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins B (apo B) and A-I
      (apo A-I) were measured. Safety and tolerability were assessed by monitoring
      routine laboratory parameters and by recording spontaneously reported side
      effects. The mean (+/- SD) baseline total cholesterol, LDL cholesterol,
      triglyceride, HDL cholesterol, apo B and apo A-I levels were 325 +/- 43, 236 +/-
      43, 128 +/- 56, 61 +/- 16, 221 +/- 60 and 164 +/- 28 mg/dl, respectively. After 6
      weeks, fluvastatin significantly (p < 0.001, ANOVA test) reduced total
      cholesterol, LDL cholesterol and apo B levels by 22%, 29% and 23%, respectively.
      These significant reductions were already reached at week 3 (total cholesterol, 
      21%; LDL cholesterol, -27%). The total cholesterol: HDL cholesterol ratio was
      reduced by 22% at week 3 and by 21% at week 6 (from 5.3 to 4.2). 78% of the
      patients showed a reduction > or = 20% for LDL cholesterol. Triglycerides were
      reduced by 16% (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517837
TI  - Serum and urinary alpha-1 microglobulin levels in renal disease.
AB  - Serum and urinary levels of alpha 1-microglobulin (AM) were measured in healthy
      volunteers and patients with varying degrees of renal insufficiency (from mild
      impairment to functionally anephric patients). In all 33 healthy volunteers, 57
      chronic renal disease and 22 functionally anephrics were studied. Serum
      creatinine (sCr) and 24-hour creatinine clearance (CCr) were used to assess renal
      function. Serum AM (SAM) increased with declining glomerular filtration and
      correlated well with CCr (r = -0.89, n = 90, P < 0.001) and sCr (r = 0.90, n =
      112, P < 0.001). sAM increased faster than sCr as the filtration function
      diminished and may be a more sensitive indicator of impairment in renal
      glomerular filtration. Urinary AM (uAM) also increased as renal filtration
      decreased and the number of functional nephrons reduced. uAM correlated with sAM
      (r = 0.62, P < 0.001) and CCr (r = -0.50, P < 0.001). uAM had a higher percentage
      increase compared with sAM during the decline in renal function but was more
      poorly correlated with CCr or glomerular filtration function. It is concluded
      that AM is useful in assessing glomerular filtration function in addition to its
      well established relevance in tubular evaluation, and has potential in the
      longitudinal assessment of changes in renal function in renal disease and
      systemic diseases that affect the kidney.

PMID- 7517838
TI  - IFCN guidelines for topographic and frequency analysis of EEGs and EPs. Report of
      an IFCN committee. International Federation of Clinical Neurophysiology.

PMID- 7517839
TI  - IFCN recommended standards for brain-stem auditory evoked potentials. Report of
      an IFCN committee. International Federation of Clinical Neurophysiology.

PMID- 7517841
TI  - Quantitative analysis of the EEG in the intracarotid amobarbital procedure. I.
      Amplitude analysis.
AB  - Thirty-seven subjects underwent bilateral internal carotid artery injections of
      amobarbital prior to surgery for intractable epilepsy. The electroencephalogram
      (EEG) of these patients was continuously monitored during these 74 procedures and
      was later subjected to quantitative analysis. Topographic mapping of these data
      suggested that the areas of inactivation were largely restricted to the anterior
      2/3 of the hemisphere injected, corresponding to the vascular distributions of
      the anterior and middle cerebral arteries. Graphical representation of the data
      demonstrated that delta and theta band activity peaked in the first 2 min post
      injection and decreased gradually thereafter, becoming stable at around 12 min
      post injection. Examination of the alpha, beta 1, and beta 2 bands suggested that
      activity increased and decreased more gradually than that for delta and theta,
      with perhaps a longer latency. Although EEG changes were most prominent in the
      anterior 2/3 of the inactivated hemisphere, similar (though smaller) changes were
      also observed in both ipsilateral and contralateral zones thought to be outside
      of the vascular distribution of the internal carotid artery.

PMID- 7517840
TI  - IFCN recommended standards for long-latency auditory event-related potentials.
      Report of an IFCN committee. International Federation of Clinical
      Neurophysiology.

PMID- 7517842
TI  - Dynamics of cognitive brain dysfunction in patients with cirrhotic liver disease:
      an event-related P300 potential perspective.
AB  - The dynamics of cognitive brain functions of 104 patients with both chronic non
      cirrhotic (NC) and cirrhotic liver disease (C: C1, non-encephalopathic; C2,
      encephalopathic) were investigated by means of visual P300 potentials elicited in
      both the paradigms of transient (PI) and selective attention (PII). Conventional
      PVEPs, psychometric tests and quantitative liver function tests were also
      performed. As compared to both an age-matched control group (N) and the non
      cirrhotic patients (NC), the N250 and P300 latencies of the cirrhotics (C) were
      equally prolonged in both P300 paradigms (P = 0.0001). By contrast, the P300
      amplitudes were not different between the patient groups in either P300 paradigm.
      In the cirrhotics, however, the P300 amplitude differences between PII and PI (+
      3.7 +/- 2.8 muV, mean +/- 1 S.D.) were significantly (P < 0.01) smaller than in
      the non-cirrhotics (+ 7.5 +/- 5.2 muV) reflecting disturbances in the dynamics of
      visual attention. Interestingly, these P300 amplitude differences between both
      paradigms were positively correlated (r = 0.35; P = 0.005) with hepatic metabolic
      capacity, but not with liver blood flow (r = 0.23; P > 0.05). The diagnostic
      efficacy of the visual P300 in PI (sensitivity, 48%; specificity, 100%) was lower
      than that of the visual P300 in PII (79%; 100%) and that of the psychometric
      tests (63%; 94%), but it remained superior to that of the PVEPs (29%; 97%). It is
      concluded that in patients with cirrhotic liver disease visual P300 potentials
      can even reveal the dynamics of minor cognitive brain dysfunction and may also
      provide interesting pathophysiological information.

PMID- 7517843
TI  - Dynamic properties of human visual evoked and omitted stimulus potentials.
AB  - Visual evoked potentials (VEPs) and omitted stimulus potentials (OSPs) are re
      examined in scalp recordings from 19 healthy subjects. The principal finding is a
      distinction in form, latency and properties between OSPs in the conditioning
      stimulus range < 2 Hz, used in previous human studies, and those in the range > 5
      Hz, used in previous studies of selected elasmobranchs, teleost fish and
      reptiles. We cannot find OSPs between 2 and 5 Hz. The high frequency ("fast,"
      ca.6- > 40 Hz) and the low frequency ("slow," ca. 0.3-1.6 Hz) OSPs have different
      forms and latencies but both tend to a constant latency after the omission, over
      their frequency ranges, suggesting a temporally specific expectation. Fast OSPs
      (typically N120, P170-230 and later components including induced rhythms at 10-13
      Hz) resemble an OFF effect, and require fixation but not attention to the
      interstimulus interval. Slow OSPs (usually P500-1100) require attention but not
      fixation; they are multimodal, unlike the fast OSPs. Based on cited data from
      fish and reptiles, fast OSPs probably arise in the retina, to be modified at each
      subsequent level. We have no evidence on the origin of slow OSPs. In both ranges
      not only large, diffuse flashes, but weak, virtual point sources (colored LEDs)
      meters away suffice. They are difficult to habituate. Both require very short
      conditioning periods. The transition from the single, rested VEP to the steady
      state response (SSR) at different frequencies is described. Around 8-15 Hz in
      most subjects larger SSRs suggest a resonance. Alternation between large and
      small SSR amplitude occurs around 4 Hz in some subjects and conditions of
      attention, and correlates with an illusion that the flash frequency is 2 Hz or is
      irregular. Jitter of the conditioning intervals greatly reduces the slow OSP but
      only slightly affects the fast OSP. Differences between scalp loci are described.

PMID- 7517844
TI  - Event-related potentials to omitted visual stimuli in a reptile.
AB  - Visual omitted stimulus potentials (OSPs) were recorded from awake pond turtles
      with arrays of 3-20 electrodes in the dorsal cortex (DC), dorsal ventricular
      ridge (DVR) and optic tectum. Since they are generally longer in duration than
      the interstimulus interval (ISI), the standard experiment is a short conditioning
      train of regular light or dark flashes (1-20 Hz) whose termination elicits the
      OSP. Tectal surface OSPs after trains > 7 Hz have 2 major positive peaks, P120
      140 and P220-250 after the due-time of the first omission; after < 7 Hz down to
      the minimum of 1.5 Hz only the slower peak appears. Some deep tectal loci also
      have one to three 100 msec wide negative waves peaking at variable times from 200
      to 1300 msec. Forebrain OSPs in DC and DVR are approximately 30 msec later and
      often include induced 17-25 Hz oscillations, not phase-locked and attenuated in
      averages. Both tectal and forebrain OSP main waves tend toward a constant latency
      after the due-time, over a wide range of ISIs, as though the system expects a
      stimulus on schedule. Jitter of ISI around the mean does not greatly reduce the
      OSP. At all loci higher conditioning rates cause the amplitudes of the steady
      state response (SSR) VEPs to decline and of the OSPs to increase. Some
      similarities and correlations of regional amplitude fluctuations between OSPs and
      VEPs are noted. The OSP dynamics are consistent with the hypothesis of a
      postinhibitory rebound of temporally specific VEP components increasingly
      inhibited with higher stimulation rates; much of this response is retinal but
      each higher brain level further modulates. OSPs in this reptile are similar to
      those known in fish and to the "high frequency" type in humans, quite distinct in
      properties from the "low frequency" OSPs. It will be important to look at the
      high frequency type in laboratory mammals to determine whether they are present
      in the midbrain and retina, as in fish and reptiles.

PMID- 7517845
TI  - IFCN recommended standards for short latency somatosensory evoked potentials.
      Report of an IFCN committee. International Federation of Clinical
      Neurophysiology.

PMID- 7517846
TI  - Night sleep does not predict day sleep in narcolepsy.
AB  - It has been suggested that the increased day sleep in narcolepsy-cataplexy is
      secondary to the known fragmentation and reduction of night sleep, there being no
      differences in 24 h sleep totals from normals. Twenty-two untreated patients
      underwent 24 h sleep wake recordings by ambulatory monitoring. Correlations were
      assessed by stepwise multiple regression between day sleep and night sleep
      measures. Almost no significant or near significant correlations emerged. It is
      concluded that day sleep in narcolepsy is based upon a different mechanism,
      perhaps a diurnal "subvigilance syndrome" of impaired arousal mechanisms.

PMID- 7517848
TI  - Comments on the paper of Soustiel et al. (1993) on a physiological coma scale.

PMID- 7517847
TI  - The influence of stimulus intensity, contralateral masking and handedness on the
      temporal N1 and the T complex components of the auditory N1 wave, by John F.
      Connolly.

PMID- 7517849
TI  - Evoked potential findings in Behcet's disease. Brain-stem auditory, visual, and
      somatosensory evoked potentials in 44 patients.
AB  - We studied 54 patients with Behcet's disease, 41 males and 13 females, mean age
      28 years. Forty-four patients had auditory brain-stem evoked potential (BAEP)
      recordings, 39 had pattern reversal visual evoked potentials (VEP), 27 had median
      nerve somatosensory evoked potential (SEP) recordings, and 25 tibial nerve SEPs.
      BAEPs were abnormal in 16 patients (52%) with neurological manifestations and in
      4 (31%) without, because of decreased amplitude of wave V, prolonged I-III or III
      V interpeak latencies, or uncertain/absent waves III and/or V. Eleven patients
      (40%) with neurological symptoms and 3 patients (25%) without, had abnormal VEPs.
      Absent potentials, decreased amplitude, with or without prolonged P100 latency,
      were found in 75% of the cases, the rest had prolonged P100 latency only. Median
      SEPs were abnormal in 8 patients (38%) with neurological manifestations. Four
      patients (21%) had abnormal tibial SEPs. Decreased amplitude with or without mild
      slowing in central conduction was the predominant SEP abnormality. SEPs were
      normal in all patients without neurological symptoms. In total, 84% of patients
      with, and 38% of patients without, neurological symptoms had abnormalities of one
      or more EP modality. When used cautiously, EP studies in Behcet's disease might
      be helpful to separate neuro-Behcet from other disorders with similar
      symptomatology, to disclose subclinical CNS involvement, to evaluate and monitor
      CNS disease activity, and to provide objective measures of treatment response.

PMID- 7517850
TI  - Subdural grid recordings of distributed neocortical networks involved with
      somatosensory discrimination.
AB  - Previous studies suggest that evidence for the sub-second activation of
      distributed neural networks can be obtained by computing the covariance between
      segments of the scalp-recorded evoked potential. However, the cortical
      representation of such potentials is not known. Here we report a case study where
      the evoked potential covariance (EPC) measure was applied to data recorded from a
      58-channel subdural grid implanted in an epilepsy patient. Recordings were made
      while the patient performed a task that required judging the somatosensory
      intensities of electrical stimuli and executing precise finger flexion responses
      in response to a subset of those stimuli. Post-stimulus EPC patterns involved
      covariances between somatosensory, motor, and temporal regions. Pre-stimulus EPC
      patterns involved these same regions, but only when it could be anticipated that
      the upcoming stimulus would likely require a response. The majority of the
      observed EPCs occurred with non-zero time-lags, and these EPCs often involved non
      adjacent electrode pairs. Thus, the observed EPCs were unlikely to arise solely
      from volume conduction. Rather, they appeared to reflect the transient
      integration of activity across distinct cortical processing nodes.

PMID- 7517851
TI  - SEP topographies elicited by innocuous and noxious sural nerve stimulation. I.
      Identification of stable periods and individual differences.
AB  - Scalp potential topographies evoked by innocuous and noxious sural nerve
      stimulation were obtained from 15 human subjects. The SEP scalp topography could
      be separated into 6 different stable periods (SP), that is, consecutive time
      points where there were no major changes in the topographic pattern. SP1
      (occurring 58-90 msec post stimulus) was characterized by a contralateral frontal
      positivity and a central negativity oriented ipsilateral to the evoking stimulus;
      SP2 (92-120 msec) by a bilateral frontal positivity and a symmetrical central
      negativity; SP3 (135-158 msec) by a widespread negativity with a minimum at the
      contralateral temporo-frontal region; and SP4 (178-222 msec), SP5 (223-277 msec)
      and SP6 (282-339 msec) by a widespread positivity with a maximum located along
      the centro-parietal midline. SP4, SP5, and SP6 could be distinguished by changes
      in the orientation of the isovoltage contour lines and/or by changes in the
      location of the maximum. The stable periods had similar onset and offset
      latencies and the same major features across subjects. However, the topographic
      patterns were not identical across subjects. These individual differences are
      likely due to the expected variability in the orientation of the equivalent
      regional dipole sources generating these potentials.

PMID- 7517852
TI  - SEP topographies elicited by innocuous and noxious sural nerve stimulation. II.
      Effects of stimulus intensity on topographic pattern and amplitude.
AB  - The effects of innocuous and noxious sural nerve stimulation on the SEP scalp
      topography were examined in 15 human subjects. This analysis focused on the 6
      stable periods (i.e., consecutive time points where the topography did not
      change) that were identified in the companion paper (Dowman 1994). Stable period
      1 (SP1: 58-90 msec post stimulus), SP4 (178-222 msec) and SP5 (223-277 msec)
      showed amplitude-stimulus intensity relationships that are similar to those of
      neurons involved in the sensory-discriminative aspects of innocuous
      somatosensation. The SP1 topographic pattern showed little or no change across
      the innocuous and noxious stimulus levels, which together with the amplitude data
      suggests that SP1 is largely generated by neurons involved in innocuous
      somatosensation. The SP4 topographic pattern did not change appreciably across
      the innocuous and noxious stimulus levels, but its amplitude decreased with
      increasing noxious stimulation. These data suggest that SP4 is generated by
      neurons involved in innocuous somatosensation and that noxious inputs inhibit
      these cells. There were differences in the SP5 topographic patterns evoked at the
      innocuous and the noxious stimulus levels, which suggest SP5 also receives a
      contribution from neurons involved in noxious somatosensation. SP3 (135-157 msec)
      and SP6 (282-339 msec) are probably generated by neurons involved in noxious
      somatosensation. The topographic patterns of both were different at innocuous and
      noxious levels. SP3's amplitude-stimulus intensity function suggests that it is
      generated by neurons that respond to noxious inputs in a non-graded fashion. The
      amplitude and offset latency of SP6 increased with increasing noxious
      stimulation, which suggests that SP6 is generated by neurons that respond to
      noxious inputs in a graded fashion.

PMID- 7517853
TI  - Neural conduction velocity of the human auditory nerve: bipolar recordings from
      the exposed intracranial portion of the eighth nerve during vestibular nerve
      section.
AB  - We measured the conduction velocity of the intracranial portion of the auditory
      nerve in 3 patients undergoing vestibular nerve section to treat Meniere's
      disease. The conduction velocity varied from patient to patient, with an average
      value of 15.1 m/sec. The latency of peak III of the brain-stem auditory evoked
      potentials (BAEPs) increased by an average of 0.5 msec as a result of exposure of
      the eighth nerve, and if that increase is assumed to affect the entire length of
      the auditory nerve (2.6 cm) evenly, then the corrected estimate of conduction
      velocity would be 22.0 m/sec. Estimates of conduction velocity based on the
      interpeak latencies of peaks I and II of the BAEP, assuming that peak II is
      generated by the mid-portion of the intracranial segment of the auditory nerve,
      yielded similar values of conduction velocities (about 20 m/sec).

PMID- 7517854
TI  - Two-channel brain-stem frequency-following responses to pure tone and missing
      fundamental stimuli.
AB  - In 2 separate experiments the brain-stem frequency-following response (FFR) was
      recorded to a pure tone (200 Hz) and complex "missing fundamental" (MF) stimuli
      differing in temporal fine structure and envelope modulation depth. FFRs were
      simultaneously recorded in 2 channels with horizontal and vertical dipole
      orientations. Horizontal electrodes were identical in both experiments (right
      left ear), but the vertical configuration was varied (vertex-left ear; vertex
      linked mastoids). The horizontal channel yielded a well defined FFR to tone
      stimulation at a latency consistent with an origin along the auditory nerve.
      However, there was no horizontal response to MF stimulation. This latter finding
      provides electrophysiological support for the conclusion that MFs are not
      directly coded in the peripheral neural response. Vertical recordings, however,
      showed equally well defined FFRs to tone and MF stimuli. Thus, a representation
      of the missing fundamental frequency is registered in the brain-stem. Vertical
      latencies were consistent with a source at the level of the lateral lemniscus.
      The FFR is well suited to elucidate certain brain-stem mechanisms of auditory
      information processing. Important additional information results when responses
      are compared in horizontal and vertical dipole orientations. Thus, the present
      results provide the first evoked response demonstration of a peripheral-brain
      stem dichotomy of MF coding.

PMID- 7517856
TI  - Event-related potentials to faces: the effects of priming and recognition.
AB  - Short-term visual memory, as in both implicit priming and explicit recognition
      tasks, can be demonstrated by decreased reaction times, the ability to
      preferentially select previously presented objects from lists and the ability to
      more readily complete previously exposed words from fragmented letters. The
      visual processing of faces occurs separately from the visual processing of non
      face stimuli, within discrete areas of bilateral posterior inferotemporal
      cortices. While visual recognition and memory of faces are independent of those
      for non-faces, their processing appears to be similar. We have demonstrated an
      electrophysiologic correlate of short-term visual memory in a face-matching
      paradigm. We have observed a series of evoked potential components consisting
      predominantly of a C140, C180 and C240 with a posterior, bitemporal distribution.
      The priming effect is reflected by a diminution of C240 amplitude in the response
      to repeated pictures of faces compared to novel pictures of faces. These data
      reflect a previously unreported set of neurophysiological observations on short
      term visual memory for faces.

PMID- 7517855
TI  - Movement-related cortical potentials preceding sequential and goal-directed
      finger and arm movements in patients with cerebellar atrophy.
AB  - To determine the influence of cerebellar involvement on the preparatory state of
      the cerebral cortex for voluntary movements, we studied the movement-related
      cortical potentials (Bereitschaftspotential, BP) preceding sequential and goal
      directed finger and arm movements in patients with cerebellar atrophy (CA). The
      first task (paradigm 1) consisted of a sequential finger movement at a self-paced
      rate of every 3 sec or longer, in which patients and control subjects pushed
      rapidly 7 keys on a keyboard in a sequence visually predetermined on a screen.
      The second task (paradigm 2) consisted of a goal-directed self-paced movement
      with visual feedback on a screen. In both paradigms, control subjects and
      patients had distinct movement-related cortical potentials, but peak amplitudes
      (close to movement onset) were reduced in the patient group (paradigm 2), whereas
      in the overall analysis the mean amplitude 600-800 msec before movement onset
      (NS1) was larger in the patient group (paradigms 1 and 2). Accordingly, the
      difference (NS2) between peak amplitude and NS1 was smaller in the patient group
      (paradigms 1 and 2). Whereas control subjects' peak amplitude (paradigm 2) and
      NS2 (paradigm 1) were focused at Cz, this topographical differentiation was
      abolished in the patient group. The onset of the BP was earlier in the patients
      than in the control subjects (paradigms 1 and 2). Our results suggest that
      pathways from the cerebellum to the cortex do play a role in generating movement
      related cortical potentials. A strong input from the cerebellum seems to be
      crucial for the generation of a normal motor potential close to the movement
      onset, reflecting a specific deficit in patients with CA. Patients with CA may
      try to compensate for their motor deficits by a longer cortical activation
      preceding voluntary movements (earlier onset of the BP). The increased NS1 could
      be the result of larger effort, by which patients try to compensate for their
      motor deficits as well.

PMID- 7517857
TI  - P3 latency jitter assessed using 2 techniques. I. Simulated data and surface
      recordings in normal subjects.
AB  - Latency variability measurement using cross-correlational techniques has the
      drawback of alignment to background noise not related to ERP activity. We
      compared latency jitter estimation in simulated and real P3 recordings using
      Woody's algorithm and a non-cross-correlational technique, the maximum likelihood
      technique (MLT). Simulated ERPs (with introduced latency jitter) were generated
      using either a 1/2 cycle 2 Hz sine wave or an averaged P3 ERP with 1 of 3 added
      noise types in 5 signal to noise ratios (SNRs): (i) white noise; (ii) a 10 Hz
      sine wave; (iii) a 7.5 Hz sine wave. Jitter measurement accuracy was assessed
      using mean square error (MSE) for 1 iteration of the Woody method and each of 4
      iterations of the MLT. Lowest MSEs occurred for higher SNRs and 1 iteration of
      the MLT. The MLT and Woody method were applied to P3 ERPs of 13 subjects with
      SNRs greater than 0.4 P3 latency jitter was significantly lower for the MLT.
      Latency jitter (both methods) did not differ between homologous electrodes and
      was highest in posterior electrodes. In the latency corrected ERP data of
      subjects with persistent alpha activity periodic components occurred in the Woody
      corrected average (not seen in the conventional or the MLT corrected averages).
      Our data indicate that the MLT is the more accurate method for determining
      latency jitter.

PMID- 7517858
TI  - Distributed current analyses of bi-hemispheric magnetic N1m responses to
      ipsi/contralateral monaural stimuli from a single subject.
AB  - Magnetoencephalographic (MEG) responses of both auditory cortices to simple
      auditory stimuli presented monaurally to either ear were recorded from a single
      subject. A distributed current model and a current dipole model were used to
      analyse the responses at the latency of the dominant N1m complex. At the N1m the
      current density was localised to a single area and was consequently well modelled
      by a single current dipole close to the peak current density. In the left
      hemisphere, the contralateral response (as identified by the peak current
      density) preceded the ipsilateral response by 3 msec. This value was 7 msec for
      the right hemisphere. Evidence was found in the right hemisphere of a posterior
      anterior movement along the sylvian fissure. Also, the left hemisphere N1m
      sources were all represented more posterior than the right hemisphere N1m
      sources.

PMID- 7517859
TI  - P300 from families.
AB  - The P3(00) event-related brain potential (ERP) was elicited using auditory and
      visual stimuli in an oddball paradigm in 10 families, each consisting of a
      biologically related father, mother, and 2 children. P3 amplitude and latency
      measures from both stimulus modalities were more highly correlated between family
      members than between non-family individuals. Similar effects were found for the
      N1, P2 and N2 components. The results support findings from twin studies
      suggesting that genetic factors contribute to P3 morphological characteristics.

PMID- 7517860
TI  - An investigation of the factors controlling the staining and destaining of
      electrophoresis gels.
AB  - A general analysis is developed for the effect of mass transport and kinetic
      parameters on the rate of staining and destaining of electrophoresis gels. The
      various contributions to these overall processes are discussed and, in
      particular, the ways in which the rate of solution flow, temperature and gel
      properties can influence staining procedures are highlighted. It is shown that
      for reproducible, rapid and uniform staining a rotating gel system, analogous to
      a rotating disc, provides the necessary controlled laminar flow. The theoretical
      equations derived are compared with experiments and it is shown that at high gel
      rotation speeds mass transport in solution does not have a major controlling
      influence on rates of staining and destaining. The temperature dependence of
      these rates also suggests that there is no significant control by the rate of
      interaction between stain and protein molecules. The major controlling factor
      under these conditions is then concluded to be the transport of stain in the gel
      itself, and the theoretical analysis and time-dependent experimental results
      allow a determination of the corresponding diffusion parameters.

PMID- 7517861
TI  - Glucose, fructose, mannose and/or glucose-1-phosphate-releasing activity stains
      for glycosidases and glycosyltransferases in gels after isoelectric focusing.
AB  - beta-Fructofuranosidase, alpha-glucosidase, beta-glucosidase, alpha-mannosidase,
      beta-mannosidase, sucrose phosphorylase, glucosyltransferase and
      fructosyltransferase were separated by isoelectric focusing and sensitively
      detected to be slightly diffuse and insoluble spots in thin-layer gels, supported
      by a glass plate, by release of monosugars or a sugar phosphate, followed by
      conversion to glucose-6-phosphate (G6P) and then by reduction of NADP+ to NADPH,
      terminated by the formation of reduced Nitroblue Tetrazolium (NBT). Approximately
      1-10 mU of enzyme was focused and the gel, after washing with a buffer, was
      partially dried and directly stained by uniformly spreading on the gel surface a
      staining medium containing sucrose or nitrophenyl glycosides as substrates,
      intermediary enzymes such as hexokinase, mutase and/or isomerase, NADP+, ATP,
      Mg+, phenazine methosulfate (PMS) and NBT. Specific staining procedures for each
      of these activities, on sucrose or on the glycosides as substrates, and staining
      procedures for multiple activities are described, with the conditions necessary
      for optimal development.

PMID- 7517862
TI  - Use of antibodies against synthetic peptides for analysis of molecular
      multiplicity: human deoxyribonuclease I polymorphism.
AB  - Eight different antibodies were raised in rabbits and chickens by injecting them
      with two synthetic N- and C-peptides, which corresponded to the N- and C-terminal
      15 residues of human deoxyribonuclease I (DNase I). These two peptides were used
      as immunogens, both free and conjugated with keyhole limpet hemocyanin (KLH). A
      rabbit antiserum against the C-peptide conjugated with KLH (rabbit anti-C/KLH)
      and two chicken antisera against the C-peptide itself (chicken anti-C) and
      conjugated with KLH (chicken anti-C/KLH) reacted well with purified DNase I,
      blotted onto a transfer membrane after isoelectric focusing in a polyacrylamide
      gel. A clear isoenzyme pattern identical to that detected with a rabbit antiserum
      against the parent enzyme (rabbit anti-DNase I) was observed. Surprisingly, the
      chicken anti-C antiserum was found to be a powerful and highly specific tool for
      the determination of urinary DNase I phenotypes (Kishi et al., Hum. Genet. 1989,
      81, 295-297) and was not inferior in any respect to the rabbit anti-DNase I.
      These findings show that the selection of immune animal is one of the most
      important factors for producing an effective anti-peptide antibody.
      Unfortunately, the anti-peptide antisera obtained in this study neither blocked
      DNase I enzyme activity nor did it bind to the enzyme.

PMID- 7517864
TI  - Three-dimensional crystal structure of the A-tract DNA dodecamer d(CGCAAATTTGCG)
      complexed with the minor-groove-binding drug Hoechst 33258.
AB  - The molecular structure of the DNA A-tract dodecamer d(CGCAAATTTGCG) complexed
      with the drug Hoechst 33258 has been determined by X-ray diffraction analysis.
      The Hoechst molecule binds in the DNA minor groove covering the sequence AATTT of
      the central A-tract, with the piperazine group close to one of the GC regions.
      The drug molecule makes two three-centered hydrogen bonds from the nitrogen atoms
      of the benzimidazole rings to the N3 and O2 atoms of the DNA bases. Although a
      high propeller twist is observed in the A-tract, only one unsymmetrical three
      centered hydrogen bond is present in the DNA major groove. The structure is
      compared with other minor-groove-binding drug complexes and the influence of
      these drugs on DNA A-tracts is discussed.

PMID- 7517865
TI  - Two human antibodies reacting with different epitopes on integrin beta 3 of
      platelets and endothelial cells.
AB  - Glanzmann's thrombasthenia is an inherited bleeding disorder that results from a
      deficit of glycoprotein (GP) IIb-IIIa complexes in platelets. Patient (EBV) is an
      adult male with GP IIb-IIIa levels < 5% of normal values and a history of blood
      transfusions. Western-blot analysis revealed a strong IgG antibody to GP IIIa in
      his plasma. The determinants were localized to the minimum-sized fragment of GP
      IIIa (50 kDa) retained on chymotrypsin-treated platelets and were lost on
      reduction of disulphides. A female patient (AF), previously described by us
      [Jallu, V., Pico, M., Chevaleyre, J., Vezon, G., Kunicki, T.J. & Nurden, A.T.
      (1992) Hum. Antibod. Hybridomas 3, 93-106] developed her anti-GP-IIIa antibody
      during pregnancy. This antibody was poorly reactive with the 50-kDa proteolytic
      fragment, yet bound to 115-kDa and 60-kDa hydrolytic products of GP IIIa.
      Antibodies from both patients recognized the GP-IIIa-like protein of endothelial
      cells, thus confirming that they were directed against the integrin beta 3
      subunit. The (EBV) antibody reacted strongly with GP IIb-IIIa in an antigen
      capture assay performed with each of a panel of four murine monoclonal antibodies
      (mAbs) recognizing different epitopes on GP IIb-IIIa. In contrast, that from (AF)
      was specifically inhibited by AP-3, a murine mAb whose epitope is thought to be
      localized between amino acids 324-422 of GP IIIa. The residual GP IIb and GP IIIa
      contents of platelets from each patient were assessed in Western blotting using
      chemiluminescence detection. SZ-22, a murine mAb to the GP IIb heavy chain (140
      kDa), located small amounts of a 130-kDa protein in (EBV) platelets. The anti-GP
      IIIa mAbs XII F9, P 37 and P 97 revealed trace amounts of protein with a relative
      mobility identical to that of GP IIIa in both (AF) and (EBV) platelets. This
      residual GP IIIa represented less than 0.5% of the amount in normal platelets.
      When, for each patient, plasma was tested in Western blotting against their own
      platelets, autoantibody activity to the residual GP IIIa was detected in both
      cases. Thus, patients (AF) and (EBV) have developed anti-GP-IIIa antibodies with
      restricted and distinct epitopes but recognizing self antigens.

PMID- 7517866
TI  - Probing the interaction of the multidrug-resistance phenotype with the
      polypeptide ionophore gramicidin D via functional channel formation.
AB  - It has been proposed that the multidrug resistance (MDR) transporter, P
      glycoprotein (P-170), may be physiologically involved in the transport of
      polypeptides. As a step towards understanding the interaction of P-170 with
      polypeptides, we isolated various gramicidin-D-resistant mammalian cell lines.
      Gramicidin D is a hydrophobic pentadecapeptide ionophore that forms proton and
      alkali metal cation-permeable channels in lipid bilayers. Gramicidin-D-resistant
      cells displayed a prominent MDR gene amplification, P-170 overexpression, reduced
      drug accumulation, and consequent resistance to MDR-type cytotoxic agents.
      Modulators of the MDR phenotype, including verapamil, reserpine and quinidine,
      rendered these cells sensitive to gramicidin D. Using these cell lines, we
      established an assay that probes for the intra-membranal interaction between P
      170 and gramicidin D. Gramicidin-D channel formation was followed by cellular
      accumulation of 86Rb+. Ionophore-resistant cells, and other MDR cells, did not
      show an appreciable increase in 86Rb+ influx rates, in the presence of increasing
      gramicidin-D concentrations. In contrast, parental cells displayed a dose
      dependent increase in the 86Rb+ influx rates. Interestingly, in the absence of
      serum, gramicidin-D-resistant cells resumed the wild-type, ionophore-dose
      dependent increase in 86Rb+ influx rates. MDR modulators caused a resumption of
      channel formation in ionophore-resistant cells. We conclude that acquisition of
      the MDR phenotype is an efficient means of cellular protection against gramicidin
      D. Hence, a new approach is offered in which P-170 interaction with gramicidin D
      is quantitatively followed by a rapid assessment of the biological activity (i.e.
      channel formation) of the substrate itself. Possible mechanisms of P-170
      interaction with free ionophore monomers, and membrane-associated gramicidin D
      are discussed.

PMID- 7517863
TI  - Polypeptide requirements for assembly of functional Sindbis virus replication
      complexes: a model for the temporal regulation of minus- and plus-strand RNA
      synthesis.
AB  - Proteolytic processing of the Sindbis virus non-structural polyproteins (P123 and
      P1234) and synthesis of minus- and plus-strand RNAs are highly regulated during
      virus infection. Although their precise roles have not been defined, these
      polyproteins, processing intermediates or mature cleavage products (nsP1-4) are
      believed to be essential components of viral replication and transcription
      complexes. In this study, we have shown that nsP4 can function as the polymerase
      for both minus- and plus-strand RNA synthesis. Mutations inactivating the nsP2
      proteinase, resulting in uncleaved P123, led to enhanced accumulation of minus
      strand RNAs and reduced accumulation of genomic and subgenomic plus-strand RNAs.
      In contrast, no RNA synthesis was observed with a mutation which increased the
      efficiency of P123 processing. Inclusion of this mutation in a P123 polyprotein
      with cleavage sites 1/2 and 2/3 blocked allowed synthesis of both minus- and plus
      strand RNAs. We conclude that nsP4 and uncleaved P123 normally function as the
      minus-strand replication complex, and propose that processing of P123 switches
      the template preference of the complex to minus-strands, resulting in efficient
      synthesis of plus-strand genomic and subgenomic RNAs and shut-off of minus-strand
      RNA synthesis.

PMID- 7517868
TI  - Site-directed mutagenesis of signal-recognition particle RNA. Identification of
      the nucleotides in helix 8 required for interaction with protein SRP19.
AB  - The RNA component of signal recognition particle (SRP) consists of eight helices
      which form a functional unit with the proteins of the SRP. The primary binding
      site of the 19-kDa protein of SRP (SRP19) is a tetranucleotide loop (tetraloop)
      in helix 6 of the SRP RNA, but additional determinants are located in helix 8,
      which might play important roles in the assembly and the function of the
      particle. To determine the structural features in helix 8 essential for
      interaction with SRP19, we altered helix 8 systematically by site-directed
      mutagenesis, and determined the ability of protein SRP19 to interact with the
      various mutant SRP RNAs. Binding of SRP19 was affected by base changes introduced
      into the 5' portion (192A, 193G, 194G in the human SRP RNA), but not into the 3'
      portion (205 A, 206G, 207C) of the distally located conserved internal loop of
      helix 8. Of the three bases at positions 192-194, only a pyrimidine at position
      192 impaired the association with SPR19. An important feature of the SRP19-RNA
      interaction were the three base pairs U195-G204, C196-G203 and G197-C202 which
      shape the helix-8 tetraloop. Some base-specific features in the base pairs were
      also recognized. The tetraloop bases of helix 8 were dispensable for the
      interaction with SRP19.

PMID- 7517867
TI  - Beta 1-integrin-mediated adhesion of melanoma cells to the propolypeptide of von
      Willebrand factor.
AB  - Cell-adhesion activity of the bovine propolypeptide of von Willebrand factor (pp
      vWF) was assessed by means of an in vitro assay with several cell lines of both
      normal and tumor-cell origin. pp-vWF promoted adhesion and spreading of B16 mouse
      melanoma cells and G-361 human melanoma cells. However, it could not induce
      adhesion of any other cell lines tested including endothelial cells, normal
      fibroblasts, and tumor cells of sarcoma, carcinoma, neuroblastoma and leukemia
      origin. A monospecific polyclonal antibody against pp-vWF, but not against
      fibronectin, laminin, and von Willebrand factor (vWF), completely blocked the pp
      vWF-mediated adhesion, indicating that the cell adhesion was due to the pp-vWF
      molecule and not due to possible contamination of these three well-known adhesive
      proteins. The cell-adhesion activity was also observed with human pp-vWF and,
      furthermore, the adhesion to both bovine and human pp-vWF was not affected by a
      peptide containing the Arg-Gly-Asp sequence while the peptide abolished the cell
      adhesion to vWF. The adhesion was completely dependent on Mg2+ and inhibited by
      Ca2+. Inhibition by an anti-(beta 1 integrin) mAb (4B4) indicates that the
      receptor for this protein belongs to the beta 1-integrin family. A monoclonal
      antibody (TC4) among several antibodies directed against bovine pp-vWF inhibited
      the B16 adhesion to immobilized pp-vWF. The epitope for this monoclonal antibody
      lies in a central 8-kDa portion of pp-vWF, suggesting that this region is
      important for the cell-adhesion activity. This idea was supported by the finding
      that purified 8-kDa fragment promoted adhesion of B16 cells in a concentration
      dependent manner. As pp-vWF shows unique cell-type specificity in its adhesion
      activity, which is completely different from that of fibronectin, laminin, vWF
      and collagen, it may be a novel type of adhesive glycoprotein that utilizes a
      beta 1-integrin receptor.

PMID- 7517869
TI  - Expression of the gene encoding alpha 1-acid glycoprotein in rabbit liver under
      acute-phase conditions involves induction and activation of beta and delta CCAAT
      enhancer-binding proteins.
AB  - Transcription of the gene encoding alpha 1-acid glycoprotein is highly induced
      during acute inflammation which has been previously shown to be mediated by some
      inducible members of the CCAAT-enhancer-binding (C/EBP) transcription-factor
      family. In this study, we demonstrate that the involved inducible C/EBP isoforms
      are C/EBP-beta and C/EBP-delta, and together they control the high-level
      induction of the alpha 1-acid glycoprotein gene in response to inflammatory
      signals. We observed that dephosphorylation severely inhibits the DNA-binding
      ability of C/EBP-delta and its transactivating potential increases in the
      presence of cellular phosphatase inhibitors, such as okadaic acid and sodium
      orthovanadate. These results suggest that C/EBP-delta is regulated by
      phosphorylation. Transient transfections using expression vectors of C/EBP-alpha,
      C/EBP-beta and C/EBP-delta have shown that while individually all three isoforms
      can transactivate the alpha 1-acid glycoprotein-chloramphenicol-acetyltransferase
      gene transcription, co-expression of C/EBP-alpha and C/EBP-beta isoforms results
      in lower levels of reporter gene expression than the levels predicted from their
      additive transactivation level. In vitro DNA-binding studies have shown that
      C/EBP-alpha and C/EBP-beta isoforms both interact and form complexes with the
      alpha 1-acid glycoprotein gene C/EBP-binding element under normal noninduced
      conditions during which alpha 1-acid glycoprotein is expressed at a very low
      level. Higher than additive levels of reporter gene expression are observed when
      combinations of C/EBP-delta and C/EBP-beta or C/EBP-delta and C/EBP-alpha are
      used. Together, these data demonstrate that C/EBP-beta and C/EBP-delta are the
      major proteins responsible for the acute-phase induction of alpha 1-acid
      glycoprotein gene expression and they require phosphorylation for transactivation
      potential.

PMID- 7517870
TI  - Induction of murine cytotoxic T lymphocytes against Plasmodium falciparum
      sporozoite surface protein 2.
AB  - Sporozoite surface protein 2 has been identified as a target of malaria vaccines
      designed to produce protective CD8+ cytotoxic T lymphocytes (CTL) because mice
      immunized with mastocytoma cells expressing a fragment of Plasmodium yoelii
      sporozoite surface protein 2 (PySSP2) are protected against malaria by an immune
      response that requires CD8+ CTL. To define CTL epitopes in the Plasmodium
      falciparum sporozoite surface protein 2 (PfSSP2), spleen cells (SC) from mice
      immunized with irradiated sporozoites (irr spz) were stimulated with synthetic
      peptides, and these effectors were tested for cytolytic activity against peptide
      pulsed, major histocompatibility complex (MHC)-matched targets. Two peptides
      containing CTL epitopes, A6 (Pf SSP2 3D7 214-233) and BH1 (Pf SSP2 3D7 3-11) were
      identified in bulk cultures of SC from immune C57BL/6 mice, and by production of
      CTL lines. Immunization with recombinant vaccinia expressing the full length
      PfSSP2 induced antigen specific, MHC-restricted, CD8+ T cell-dependent cytolytic
      activity against these two peptides. Finally, CTL were induced by immunization
      with a bacteria-derived recombinant fragment of PfSSP2 (rPfSSP2) mixed with a
      liposomal formulation containing a cationic lipid (Lipofectin Reagent, LPF).
      Induced CTL lysed target cells pulsed with peptide A6 or with LPF/rPfSSP2, but
      not targets pulsed with only rPfSSP2. These studies demonstrate that CTL specific
      to PfSSP2 are present in C57BL/6 mice and that immunization with purified rPfSSP2
      delivered with LPF induces a cytotoxic T cell response.

PMID- 7517871
TI  - Human immunodeficiency virus-1 reverse transcriptase immunodominant CD4+ T cell
      epitopes: a peptide-based multiparametric assessment in the mouse.
AB  - We previously identified an immunodominant CD4+ T cell determinant in the carboxy
      terminal region of HIV-1 reverse transcriptase (RT528-543). The present study
      aimed at enumerating all the potential sites of HIV-1 RT recognized by Th cells
      in the BALB/c (H-2d) mouse model. To achieve this we used a panel of 62
      overlapping 15-mer synthetic peptides covering the whole RT sequence to assay the
      following parameters: (i) immunogenicity in naive BALB/c mice injected either
      with peptides pools or individual peptides; (ii) antigenicity, as detected by
      their ability to restimulate in vitro T cells from BALB/c mice primed with native
      RT; (iii) MHC class II (Ad)-binding capacity as measured by the inhibition of the
      antigen-specific, Ad-restricted presentation of unfolded apamin (4-Acm) by fixed
      antigen-presenting cells to Ad/4-Acm-specific, interleukin-2-producing T
      hybridoma cells; and (iv) the presence of typical or degenerate consensus Ad
      binding motifs. The results in this study permitted identification of three novel
      immunodominant RT mouse CD4+ T cell sites (RT276-290, RT375-389 and RT411-425)
      located in regions of limited polymorphism among RT from several HIV isolates.
      Some of these RT segments were found to be in the vicinity of B cell or H-2Kk- or
      HLA-A2-restricted cytotoxic T lymphocyte epitopes. Finally, the approach used in
      this study was found to be very efficient for enumerating most T cell recognition
      sites in a complex protein, a result that would have not been achieved by a
      single parameter-based analysis.

PMID- 7517872
TI  - CD57+ T lymphocytes are derived from CD57- precursors by differentiation
      occurring in late immune responses.
AB  - CD3+ T cells expressing the 110-kDa CD57 antigen are found in survivors of renal,
      cardiac and bone marrow transplants, in patients with acquired immune deficiency
      syndrome and in patients with rheumatoid arthritis. They are also present in
      normal individuals and expand upon ageing. They do not grow in culture and their
      role in the immune response is poorly understood. The expression of the various
      isoforms of the leukocyte common antigen (CD45) identifies a spectrum of
      differentiation in CD4+ and CD8+ T cells ranging from naive
      (CD45RA+CD45RBbrightCD45RO-) through early primed cells (CD45RA-RBbrightROdull)
      to highly differentiated memory cells which are CD45RA-RBdullRObright. CD45
      isoforms expressed by CD57+ T cells showed distinct differences between CD4+ and
      CD8+ populations, but in each case indicated an advanced state of
      differentiation. The expression of T cell receptor V beta families was highly
      variable between individuals, but both CD57+ and CD57- cells show a full range of
      the specificities tested. V beta expression was more closely related within
      either the CD4+ or the CD8+ subsets, irrespective of CD57 expression, than
      between these subsets, suggesting a relationship between CD57+ and CD57- cells
      within the same T cell pool. This possibility was supported by experiments
      showing that CD3+CD57+ lymphocytes were similar to CD3+CD57- T cells in terms of
      the production of basic T cell cytokines [interleukin (IL)-2, IL-4, and
      interferon-gamma]. Furthermore, in vitro stimulation of CD3+CD57- T cells in
      secondary mixed leukocyte reaction or by co-culture with IL-2 and IL-4 induced
      the appearance of CD3+CD57+ cells with phenotypic and functional similarities to
      in vivo CD3+CD57+ cells. These data strongly suggest that the expression of CD57
      is a differentiation event which occurs on CD57- T cells late in the immune
      response.

PMID- 7517873
TI  - Fine antigen specificity of human gamma delta T cell lines (V gamma 9+)
      established by repetitive stimulation with a serotype (KTH-1) of a gram-positive
      bacterium, Streptococcus sanguis.
AB  - We have established human gamma delta T cell lines specific for Streptococcus
      sanguis (S. sanguis) KTH-1 present in normal oral cavity flora. The CD4-CD8-CD3+V
      gamma 9+V delta 1-CD45RO+ CD25+ T cell lines showed a proliferative response to
      the streptococcal antigen (Ag) in the presence of autologous antigen-presenting
      cells without apparent evidence of HLA restriction. The proliferative response of
      the gamma delta T cell lines was completely blocked by anti-TcR gamma delta
      monoclonal antibody (mAb) and anti-HLA class I mAb (W6/32), whereas anti-HLA
      classical class Ia mAb (B-H9; anti-HLA-A,B,C), anti-HLA class II mAb (anti-DR,
      anti-DQ, and anti-DP) and anti-CD4 mAb did not have any inhibitory effects.
      Surprisingly, the gamma delta T cell lines showed the proliferative response
      against the original bacterial Ag KTH-1 exclusively, and exhibited no cross
      reactivity with nominal Ag such as purified protein derivative of tuberculin,
      tetanus toxoid and Mycobacterium tuberculosis, or the same species but different
      strain of S. sanguis, American Type Culture Collection (ATCC) standard strain
      (10556), or even with the same strain but different serotype of S. sanguis, KTH
      3. Moreover, cytokine production of the gamma delta T cell lines was similar to
      the Th1 pattern [interferon-gamma, tumor necrosis factor (TNF)-alpha and TNF
      beta]. They also produced interleukin-8 that functions as one of chemoattractants
      for polymorphonuclear cells. Using direct sequencing technique of the polymerase
      chain reaction products, we found that junctional diversity of the T cell
      receptor (TcR) used by the parental KTH-1 specific gamma delta T cell line and
      its subclones is rather limited. It is suggested that gamma delta T cells with
      canonical TcR could preferentially respond to KTH-1 Ag. Thus, in addition to a
      broad or cross-reactivity of gamma delta T cells against phylogenetically
      conserved stress/heat-shock protein, which is well characterized by others, some
      peripheral blood gamma delta T cells could recognize and kill exogenous agents
      with fine antigenic specificity to protect the body against them.

PMID- 7517874
TI  - CD4 engagement induces Fas antigen-dependent apoptosis of T cells in vivo.
AB  - CD4 is a T lymphocyte receptor for major histocompatibility complex class II
      antigens. It is referred to as coreceptor because it synergizes with the T cell
      receptor for antigen when both receptors become engaged simultaneously. We show
      here in mice that when engaged by antibody independently of the T cell antigen
      receptor, CD4 induces T cells to undergo apoptosis. Several features of this
      process were identified. The expression of an intact Fas protein is a requirement
      for CD4-mediated T cell death. Mice homozygous for the lpr mutation which are
      defective in the expression of Fas and in their ability to delete lymphocytes
      apoptotically fail to delete anti-CD4-reactive T cells. Sessile anti-CD4-reactive
      T cells leave their homing environment in lymphoid organs and modulate their cell
      surface molecules, e.g. CD2, CD3, CD4. A massive influx of lymphoid cells with
      null-cell phenotype occurs in the blood where they begin to reexpress cell
      surface markers. With their arrival in the circulation, anti-CD4-reactive T cells
      develop features of DNA degradation typical of apoptosis. More than one third of
      the circulating lymphoid cells show apoptotic features 7-8 h after anti-CD4
      injection. Their frequency declines subsequently presumably due to their physical
      disintegration via shedding of apoptotic bodies and phagocytosis. Our data show
      that when not obliged to the activation process by the antigen receptor, CD4 can
      mediate deletion signals. Thus, besides functioning as coreceptor with the
      antigen receptor, CD4 has a function of its own in facilitating the induction of
      apoptosis.

PMID- 7517875
TI  - Multiple self epitopes on the Rhesus polypeptides stimulate immunologically
      ignorant human T cells in vitro.
AB  - The extent of autoreactive T cell repertoire in the normal individual has
      previously been unclear. Here we demonstrate that T cells from healthy humans can
      be stimulated by multiple epitopes on a self protein to give primary
      proliferative responses in vitro. Synthetic 15-mer peptides, corresponding to the
      sequence of a human red blood cell Rhesus polypeptide, were tested for the
      ability to stimulate normal T cells. Multiple peptides were found to provoke
      responses reproducibly, and the proliferation could be blocked consistently by
      antibodies to HLA-DR, but not -DP or -DQ. T cells from each donor proliferated in
      response to different patterns of peptides, but this variation in pattern was
      less marked in individuals with the same HLA-DR type. The responses were
      comparable in kinetics to those elicited by the non-recall foreign antigen
      keyhole limpet hemocyanin, and the responding cells are most commonly derived
      from the CD45RA+ subpopulation, indicating that they had not been activated in
      vivo. It is considered that T cells are "immunologically ignorant" of many self
      peptides, presumably because they correspond to cryptic epitopes that are not
      normally presented in vivo.

PMID- 7517877
TI  - Expression and function of CD59 on colonic adenocarcinoma cells.
AB  - The expression and function of CD59, a 19-25 kDa membrane glycoprotein that
      inhibits formation of the membrane attack complex of complement, was analyzed on
      normal and malignant human colonic epithelial cells. Analysis by
      immunofluorescence demonstrated a weak apical expression of CD59 on normal
      intestinal epithelium, with an increased expression on adenocarcinoma cells. The
      expression of CD59 was greatest on tumor cells with poor differentiation. The
      functional activity of CD59 on human adenocarcinoma cells was investigated using
      the colonic adenocarcinoma cell line HT29. CD59 on HT29 cells was glycosyl
      phosphatidylinositol-linked, and had a molecular mass of 19-25 kDa. HT29 cells
      expressed approximately four times more CD59 than leukocytes, and showed a high
      resistance to antibody-dependent complement-mediated lysis. Blocking of CD59 with
      divalent antigen-binding F(ab')2 fragments of the anti-CD59 monoclonal antibody
      1F5 resulted in a dose-dependent increase in complement-mediated lysis,
      suggesting that CD59 may be of importance in protecting colonic adenocarcinoma
      cells against complement-mediated cytolysis.

PMID- 7517878
TI  - Lipopolysaccharide-dependent transactivation of the temporally regulated
      immunoglobulin heavy chain 3' enhancer.
AB  - To execute different biological functions, the expression pattern of
      immunoglobulin heavy chain genes (IgH) is altered during B lymphocyte
      differentiation. Early in B cell differentiation, it is assumed that the heavy
      chain promoter and the intragenic enhancer (E mu) ensure VDJ recombination. This
      leads to the expression of the immunoglobulin receptor on the cell surface. An
      additional strong enhancer in the far 3' end of the IgH locus has, however,
      prompted a re-evaluation of the regulation of immunoglobulin gene expression. To
      define the temporal and spatial regulation of the IgH 3' enhancer, transgenic
      mice harboring an enhancer-dependent reporter gene construct were generated. Here
      we demonstrate that IgH 3' enhancer activity is largely restricted to activated
      immunocompetent B cells. Furthermore, the enhancer can be transactivated
      following mitogen stimulation with lipopolysaccharide and 12-O
      tetradecanoylphorbol 13-acetate. We propose a model whereby 3' enhancer
      activation is linked to the activation of resting immunocompetent B cells. The
      implications of the enhancer being active in late B lymphocyte differentiation,
      when heavy chain class switching occurs, are discussed.

PMID- 7517876
TI  - The degradation product of the C5a anaphylatoxin C5adesarg retains basophil
      activating properties.
AB  - The complement cleavage product C5a is a potent agonist of different leukocyte
      types and also has anaphylatoxic properties through the release of mediators by
      basophils and tissue mast cells. C5a is very rapidly degraded by serum
      carboxypeptidase N which cleaves the functionally important carboxy-terminal
      arginine, generating C5desarg, a chemotactic agonist with little mast cell
      activating ability. Here we show that natural human C5adesarg is still a trigger
      for basophil mediator release superior to other endogenous IgE-independent
      agonists such as monocyte chemotactic protein (MCP)-1, interleukin (IL)-8, C3a
      and platelet-activating factor. On a molar basis C5adesarg is only one order of
      magnitude less potent and about half as efficacious as C5a at inducing basophil
      degranulation. Priming of basophils with either IL-3, IL-5, granulocyte
      macrophage-colony-stimulating factor (GM-CSF) or nerve growth factor (NGF) (with
      comparable efficacies, but different potencies: IL-3 > NGF > IL-5 > GM-CSF)
      enhanced histamine release and conditioned the cells to produce large amounts of
      leukotriene C4 (LTC4), which is not generated by basophils exposed to C5adesarg
      alone. The efficacy of C5a and C5adesarg at inducing histamine and LTC4 release
      by primed basophils was similar. Thus, C5adesarg is a stable inducer of release
      of inflammatory mediators by human basophils, particularly in primed cells, and
      complement may, therefore, play a role in immediate-type hypersensitivity
      diseases in allergic late-phase reactions.

PMID- 7517879
TI  - Lymphocyte populations and immune responses in CD5-deficient mice.
AB  - The CD5 antigen is expressed at a high level on T cells from early on in
      thymocyte ontogeny and continues to be expressed on the surface of all mature T
      cells. In addition, it marks a population of B lymphocytes (B-1a) with distinct
      physiological properties. To study the in vivo function of CD5, the murine gene
      was inactivated using the technique of homologous recombination in embryonic stem
      cells. In homozygous mutant mice the CD5 antigen is not expressed on the surface
      of either T or B lineage cells, indicating that in both cell populations this
      antigen is encoded by the same gene. CD5-deficient (CD5T) mice are healthy and
      populations of T and B lymphocytes in these mice look unchanged when compared to
      control mice. The mutant mice are able to mount effective immune responses to T
      cell-dependent and -independent antigens.

PMID- 7517882
TI  - Hypothermia induced by cholinomimetic drugs is blocked by galanin: possible
      involvement of ATP-sensitive K+ channels.
AB  - Central administration of galanin in the mouse dose-dependently blocked the
      hypothermia induced by the muscarinic receptor agonist, 2-ethyl 8-methyl-2,8
      diazospiro[4,5]decan-1,3-dion hydrobromide, RS86 (minimum effective dose, MED = 3
      nmol) and the acetylcholinesterase inhibitor tetrahydroaminoacridine, (MED = 3
      nmol). This inhibitory effect was reversed over the dose range (0.1, 0.3, 1, 3
      nmol) by the galanin receptor antagonist galantide (MED = 0.3 nmol). Furthermore,
      the ATP-sensitive K+ channel blockers glibenclamide (MED = 1 nmol) and gliquidone
      (10 nmol) both prevented the inhibitory effects of galanin on RS86 induced
      hypothermia. Glibenclamide (10 nmol) also reversed the inhibitory effects of
      galanin on tetrahydroaminoacridine induced hypothermia. Preincubation of rat
      cortical membranes with galanin (10 nM, 1000 nM) in vitro had no effect on
      binding affinity, receptor number or pharmacology of the rat cortical muscarinic
      receptor. In contrast to the high affinity of glibenclamide, galanin only weakly
      displaced [3H]glibenclamide binding in mouse whole brain homogenates (36% at 10
      microM). These studies suggest that the inhibitory effect of galanin on
      cholinergically mediated hypothermia induced by RS86 and tetrahydroaminoacridine
      may be exerted via an action at ATP-sensitive K+ channels but is unlikely to be
      acting directly at the site labelled by [3H]glibenclamide.

PMID- 7517880
TI  - CHF 2206, a new potent vasodilating and antiaggregating drug as potential nitric
      oxide donor.
AB  - The effects of the new 3,4-disubstituted furoxan, CHF 2206, on vascular tone,
      platelet aggregation and platelet cyclic 3',5'-guanosine monophosphate (cGMP)
      levels were investigated. The compound was a potent inhibitor of rabbit aortic
      ring contraction induced by norepinephrine, the stable prostaglandin F2 alpha
      analogue, U-46619, and KCl; this activity was independent of endothelium
      integrity. When pre-incubated with platelet-rich plasma, CHF 2206 potently
      reduced in a dose-dependent manner the aggregation induced by the threshold
      aggregating concentration of collagen, ADP or platelet activating factor (PAF).
      In the same experimental conditions, the test compound increased the platelet
      cGMP levels and this rise was clearly associated with the inhibition of platelet
      aggregation. Moreover, 3-isobutyl-1-methyl-xanthine (IBMX) 5 microM potentiated
      the antiaggregating activity of CHF 2206. These results indicate that the
      increase in cGMP plays a key role in the CHF 2206-elicited responses.
      Oxyhemoglobin reduced all the pharmacological actions of the test compound. This
      evidence, along with the capacity of CHF 2206 to cause inorganic nitrite
      production in the presence of platelet-rich plasma, strongly suggests that nitric
      oxide (NO) may be a common reactive intermediate responsible for the effects
      induced by the drug. In conclusion, the furoxan derivative CHF 2206 exerts a
      potent antiaggregating and vasodilating activity with a pharmacological profile
      similar to the one described for NO-donating pro-drugs.

PMID- 7517881
TI  - Effects of d-fenfluramine on feeding and hypothalamic 5-hydroxytryptamine and
      dopamine in male and female rats.
AB  - Male and female rats were given d-fenfluramine and its effects on feeding and on
      hypothalamic concentrations of the drug, its metabolite norfenfluramine and 5
      hydroxytryptamine (5-HT) and dopamine determined. ID50 values (i.p.) for the
      hypophagic effect of the drug on 30-, 42- and 100-day-old rats measured over 2 h
      during the light phase after 24 h food deprivation did not vary significantly
      with sex but tended to decrease with age approximately in parallel with daily
      percentage increases and (after deprivation) of decreases in body weight.
      However, male but not female 30-day-old rats showed a rebound of feeding during
      the subsequent 2 h. ID50 values of 42-day-old rats on a palatable diet or
      measured during the dark phase when freely feeding also did not vary with sex.
      Male 30-day-old rats killed at 2-10 h after an ID75 (p.o.) dose of d-fenfluramine
      had substantially lower hypothalamic concentrations of the drug and comparable or
      slightly lower concentrations of its metabolite norfenfluramine than 30-day-old
      females. Similarly treated 100-day-old males also had lower concentrations of
      fenfluramine but significantly higher norfenfluramine levels than females so that
      drug plus metabolite concentrations were essentially independent of sex. 100-day
      old females killed 2 h, 24 h and 7 days after d-fenfluramine (3.8 mg/kg p.o. =
      ID75) had larger percentage decreases of hypothalamic 5-HT than identically
      treated males. Percentage decreases of 5-HT and 5-hydroxyindoleacetic acid (5
      HIAA) tended to become less marked with time after injection in males but not
      females.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517883
TI  - Central serotoninergic system involvement in the anorexia induced by NG-nitro-L
      arginine, an inhibitor of nitric oxide synthase.
AB  - The effects of NG-nitro-L-arginine, an inhibitor of brain nitric oxide (NO)
      synthase, on central serotoninergic system were studied in male obese Zucker rats
      and in their lean age-matched controls (FA/?; FA/FA), both groups aged 14 weeks.
      Acute injection of NG-nitro-L-arginine (50 mg/kg i.p.) or repeated administration
      of NG-nitro-L-arginine (50 mg/kg i.p. daily, for 7 days) reduced food intake and
      body weight in obese rats. Acute administration of NG-nitro-L-arginine reduced
      food intake in lean rats. However, lean rats showed tolerance to the NG-nitro-L
      arginine effects after repeated administration. NG-Nitro-L-arginine
      administration significantly increased serotonin metabolism in the cortex,
      diencephalon and medulla-pons of obese Zucker rats after either acute or repeated
      administration of NG-nitro-L-arginine. In contrast, NG-nitro-L-arginine increased
      serotonin metabolism in lean rats only after acute administration, and the
      appearance of tolerance to NG-nitro-L-arginine anorectic effects paralleled the
      failure of NG-nitro-L-arginine to increase serotonin metabolism. The present data
      extend our previous findings indicating that NG-nitro-L-arginine possesses
      anorectic activity in obese Zucker rats, and clearly suggest that the central
      serotoninergic system mediates the anorexia induced by inhibitors of brain NO
      synthase.

PMID- 7517884
TI  - Functional evidence that balloon angioplasty results in transient nitric oxide
      synthase induction.
AB  - Since serious vasospastic episodes limit the efficacy of percutaneous
      transluminal coronary angioplasty, this study has examined the time-dependent
      changes in vascular reactivity that occur following rat carotid artery balloon
      angioplasty. Relative to vessels from sham-operated animals, angioplasty caused
      an immediate increase in endothelin-1 contractile potency, an observation not
      made with noradrenaline or KCl, implicating endothelin-1 in the pathogenesis of
      acute arterial vasospasm. This hyperreactivity, possibly resulting from the loss
      of endothelin-1-induced nitric oxide release from the endothelium, was transient
      and was followed by a non-specific decrease in reactivity to all three
      spasmogens. Since the delayed reduction in endothelin-1 contractile potency was
      restored by N omega-nitro-L-arginine methyl ester, this hyporeactivity appeared
      to result from nitric oxide synthase induction. Furthermore, since the
      regenerating endothelium was dysfunctional, the generation of nitric oxide was
      from a non-endothelial source (possibly the smooth muscle or infiltrating
      macrophages). This response may function to ameliorate the spasmogenic and
      proliferative actions of chronically acting vasoactive factors and oppose
      platelet aggregation.

PMID- 7517885
TI  - Different Ca2+ influx pathways mediate tachykinin receptor-induced contraction in
      circular muscle of guinea-pig colon.
AB  - We used an electrophysiological approach (single sucrose gap) to compare the
      mechanism of action of selective tachykinin NK1 and NK2 receptor agonists
      ([Sar9]substance P sulfone and [beta ala8]neurokinin A-(4-10), respectively) in
      producing contraction of the circular muscle of the guinea-pig proximal colon.
      [Sar9]Substance P sulfone produced a marked depolarization, action potentials and
      increase in membrane conductance. On the other hand, [beta Ala8]neurokinin A-(4
      10) produced less depolarization of the cell membrane and did not change membrane
      resistance. Nifedipine (1 microM) greatly reduced (80% inhibition) the
      contraction due to [Sar9]substance P sulfone while that due to [beta
      Ala8]neurokinin A-(4-10) was slightly affected (13% inhibition). Action
      potentials induced by either agonist were suppressed by nifedipine, while
      depolarization was reduced only to a minor extent. When tested in a Ca(2+)-free
      medium, the contraction produced by either agonist was greatly reduced (84-89%)
      as compared to the control. In organ bath experiments [Sar9]substance P sulfone
      and [beta Ala8]neurokinin A-(4-10) produced concentration-dependent contraction
      of the circular muscle of the colon (EC50 8 and 12 nM, respectively). Nifedipine
      (1 microM) markedly suppressed the response to [Sar9]substance P sulfone while
      that to [beta Ala8]neurokinin A-(4-10) was only slightly depressed. These
      findings demonstrate that NK1 receptor-mediated contraction is strictly linked to
      membrane depolarization and action potentials generation through nifedipine
      sensitive Ca2+ channels (electromechanical coupling) while the NK2 receptor
      mediated contraction is substantially unrelated to depolarization and, while
      being largely dependent upon extracellular Ca2+, is nifedipine-resistant,
      possibly linked to the opening of non-selective (Ca(2+)-permeable) receptor-gated
      cation channels (pharmacomechanical coupling).

PMID- 7517886
TI  - Effect of interventions that increase cyclic AMP levels on susceptibility to
      ventricular fibrillation in unanesthetized dogs.
AB  - Although the autonomic nervous system has been implicated in the formation of
      ventricular fibrillation, the precise mechanism by which this is mediated remains
      undetermined. In particular, the role of second messengers, generated by beta
      adrenoceptor activation, has been postulated to mediate the pro-arrhythmic
      effects of the sympathetic nervous system. Thus, a 2 min occlusion of the left
      circumflex coronary artery was initiated during the last minute of exercise in
      canines with healed myocardial infarctions (produced by ligation of left anterior
      descending artery). Fifteen dogs were found to be susceptible to the formation of
      ventricular fibrillation while 17 animals were resistant. Nine resistant dogs
      were treated with the phosphodiesterase inhibitor isobutylmethyl xanthine (IBMX,
      1 mg/kg) in combination with an infusion of 8-bromo-cAMP (100-150
      micrograms/kg/min beginning 45 min prior to exercise). Heart rate and left
      ventricular dP/dtmax significantly increased, but failed to elicit, arrhythmias
      during the exercise and ischemia test. Nine resistant animals were also treated
      with the adenylate cyclase activator forskolin, (100 micrograms/kg), which
      provoked the same hemodynamic changes as the cyclic AMP infusion but also failed
      to induce ventricular fibrillation. Both forskolin (n = 3) and IBMX (n = 3)
      induced large increases in myocardial cAMP levels (control 5.2 +/- 0.5, forskolin
      8.1 +/- 0.8 pmol/mg non-collagen protein; control 5.0 +/- 0.8, IBMX 6.8 +/- 0.3
      pmol/mg non-collagen protein). Ten resistant animals were treated with the beta
      adrenoceptor agonist isoproterenol (1-10 micrograms/kg/min), which failed to
      cause ventricular fibrillation despite significant increases in the hemodynamic
      parameters described above. Finally, experiments were repeated after 8-bromo-cAMP
      infusion and IBMX pretreatment in 8 susceptible animals with pharmacologic
      denervation (atropine+propranolol+prazosin). In spite of hemodynamic increases
      indicative of an increase in myocardial cyclic AMP levels, arrhythmias were not
      re-introduced. These data suggest that changes in cAMP may not be responsible for
      ventricular fibrillation in this model of sudden cardiac death.

PMID- 7517887
TI  - Effect of platelet-activating factor and its antagonists on colonic dysmotility
      and tissue levels of colonic neuropeptides.
AB  - We investigated whether platelet-activating factor (PAF) alters colonic tissue
      levels of substance P and vasoactive intestinal peptide (VIP), two neuropeptides
      that regulate colonic motility. Left colons were harvested from NZ White Rabbits
      and underwent vascular perfusion via the inferior mesenteric artery. Strain gauge
      transducers were sewn onto the serosal surface of the colon to evaluate colonic
      motility. Colons were perfused with either buffered saline alone or with 5.0 x
      10(-5) M PAF. PAF administration increased tissue VIP and substance P levels and
      decreased the force of colonic contractions. Pretreatment with WEB-2170 or
      alprazolam decreased concentrations of both tissue neuropeptides, and decreased
      the force of colonic contractions and minute motility index. These results
      suggest that both VIP and substance P are stimulated by PAF and may participate
      in colonic dysmotility during inflammatory states.

PMID- 7517888
TI  - Nitric oxide synthase inhibitors 7- and 6-nitroindazole relax smooth muscle in
      vitro.
AB  - 7-Nitroindazole induced concentration-dependent relaxation of precontracted
      rabbit aorta, dog middle cerebral artery, rat anococcygeus muscle and rat stomach
      fundus. Relaxations to 7-nitroindazole in rabbit aorta were unaffected by nitric
      oxide synthase blockade or endothelial removal. 6-Nitroindazole also caused
      concentration-dependent relaxation in dog middle cerebral artery and rabbit
      aorta, being equipotent with 7-nitroindazole in both tissues. These data suggest
      that indazole derivatives can induce an endothelium- and nitric oxide synthase
      independent relaxation of smooth muscle in vitro.

PMID- 7517889
TI  - Protective effect of the metabotropic glutamate receptor agonist, DCG-IV, against
      excitotoxic neuronal death.
AB  - (2S,1'R,2'R,3'R)-2-(2,3-Dicarboxycyclopropyl)glycine (DCG-IV), a potent agonist
      of subtypes 2 and 3 of metabotropic glutamate receptors (mGluR2 or 3), protected
      cultured cortical neurons against excitotoxicity induced either by a brief
      exposure to N-methyl-D-aspartate (NMDA) or a prolonged exposure to kainate. As a
      neuroprotective agent, DCG-IV was much more potent than the mixed agonists 1S,3R
      aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) or (2S,1'S,2'S)-2
      (carboxycyclopropyl)glycine (L-CCG-I), suggesting a neuroprotective role for
      mGluR2 or 3 against excitotoxic neuronal death.

PMID- 7517890
TI  - Role of Ca2+ in the vascular contraction caused by a thrombin receptor activating
      peptide.
AB  - Thrombin receptor activating peptide (TRAP) caused a slowly developing, sustained
      contraction of endothelium denuded rat aortic rings. Both nifedipine (10 microM)
      and removal of Ca2+ from the physiological salt solution (PSS) caused significant
      (60-75%) reductions in the contractile response to TRAP. In Ca(2+)-free PSS the
      response to both phenylephrine and TRAP were markedly reduced. Readministration
      of Ca2+ quickly restored the full response to phenylephrine. In contrast,
      readministration of Ca2+ only partially restored the TRAP response. Depletion of
      TRAP-sensitive intracellular Ca2+ stores had no effect on the phenylephrine
      response in Ca(2+)-free PSS. A threshold contracting concentration of TRAP (10
      microM) enhanced contractions to the activator of voltage regulated Ca2+ channels
      Bay K 8644. Similarly, Bay K 8644 enhanced responses to TRAP. It is concluded
      that the contractile response of rat aortic rings to TRAP is largely mediated by
      influx of extracellular Ca2+. Furthermore, the intracellular Ca2+ pool(s)
      activated appears to be different from the phenylephrine-sensitive pools, which
      cannot be depleted by TRAP.

PMID- 7517891
TI  - Non-peptide angiotensin receptor antagonists bind to tachykinin NK3 receptors of
      rat and guinea pig brain.
AB  - [3H]Senktide, a highly selective tachykinin NK3 receptor agonist, was used to
      study tachykinin NK3 receptors of rat and guinea pig brain. Guinea pig brain
      membranes had a Kd of 3.9 +/- 0.5 nM and a Bmax of 42 fmol/mg. Dose-displacement
      experiments with neurokinins and selective tachykinin receptor agonists revealed
      the following order of potency: [MePhe7]neurokinin B > neurokinin B > substance P
      > neurokinin A. This order is typical for a tachykinin NK3 receptor. To further
      characterize the specificity of this receptor, the effects of unrelated compounds
      such as: bradykinin, angiotensin II, bombesin and their structural analogs were
      also evaluated on the binding of [3H]senktide. Unexpectedly, the angiotensin AT1
      receptor antagonists, DuP 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H
      tetrazol-5-yl)bip hen yl-4-yl)methyl]imidazole potassium salt), L-158,809 (5,7
      dimethyl-2-ethyl-3-[(2'-(1H-tetrazol-5-yl) [1,1'-biphenyl]-4-yl) methyl]-3H
      imidazo[4,5-beta]pyridine H2O) and EXP 3174 (2-n-butyl-4-chloro-1-[2'-(1H
      tetrazol-5-yl)biphenyl-4-yl)methyl]i midazole- 5-carboxylic acid), inhibited the
      binding of [3H]senktide to its receptor in the guinea pig brain membranes with
      IC50 values of 18 microM, 25 microM and 50 microM, respectively. Similar effects
      were also observed with rat brain membranes. Angiotensin II, saralasin
      ([Sar1,Val5,Ala8]angiotensin II, a peptide angiotensin AT1 receptor antagonist)
      and PD 123,319 (1-[4-(dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl)-4,5,
      6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid, a known non-peptide
      angiotensin AT2 receptor antagonist) did not inhibit the binding of [3H]senktide
      to either type of membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517893
TI  - Hypoxic coronary vasodilatation and cGMP overproduction are blocked by a nitric
      oxide synthase inhibitor, but not by a guanylyl cyclase ANF receptor antagonist.
AB  - Myocardial hypoxia is known to be accompanied by the release of atrial
      natriuretic factor (ANF), a peptide which dilates the coronary vessels by
      stimulating particulate guanylyl cyclase. We have assessed whether ANF plays a
      paracrine role in hypoxic coronary vasodilatation, a reaction which we had
      previously found to be associated with increased cyclic GMP production. Compound
      HS 142-1 (100 micrograms/ml), a specific antagonist of the guanylyl cyclase ANF
      receptor, inhibited by 50-70% the coronary-vasodilating effects of human ANF (1
      10 micrograms) administered to isolated guinea pig hearts, but affected neither
      hypoxic coronary vasodilation nor cyclic GMP overflow. In contrast, the nitric
      oxide synthase inhibitor N omega-methyl-L-arginine (300 microM) reduced hypoxic
      coronary vasodilatation and cyclic GMP overproduction by approximately 70% and 50
      60%, respectively. Thus, unlike nitric oxide, ANF appears not to play a paracrine
      role in hypoxic coronary vasodilatation.

PMID- 7517895
TI  - Signal transduction of the GLP-1-receptor cloned from a human insulinoma.
AB  - GLP-1 (glucagon-like peptide 1 (7-36) amide) plays an important role in the
      regulation of insulin secretion and proinsulin gene expression of pancreatic beta
      cells. Patients with insulinoma tumors show uncontrolled insulin hypersecretion.
      This study demonstrates the molecular cloning of a cDNA for the GLP-1 receptor
      from a human insulinoma employing a lambda-gt11 cDNA library. The cloned cDNA
      encoded a seven transmembrane domain protein of 463 amino acids which showed high
      homology to the GLP-1 receptor in normal human pancreas. Four amino acid
      exchanges were found in comparison to a receptor sequence obtained from regular
      pancreatic islets. When transfected transiently into COS-7 or stably into
      fibroblast CHL cells a high affinity receptor was expressed which coupled to the
      adenylate cyclase with normal basal cAMP and increasing intracellular cAMP levels
      under GLP-1 stimulation. The receptor accepted GLP-1 and the non-mammalian
      agonist exendin-4 as high affinity ligands. In transfected COS-7 cells, GLP-1 did
      not influence intracellular calcium, whereas in the stably transfected
      fibroblasts GLP-1 transiently increased intracellular calcium to a small extent.
      The understanding of GLP-1 receptor regulation and signal transduction will aid
      in the discovery of compounds that act as agonists of the GLP-1 receptor for
      potential use in the treatment of diabetes and will facilitate the understanding
      of its expression under normal and pathophysiological conditions.

PMID- 7517894
TI  - Aging effects on hepatic NADPH cytochrome P450 reductase, CYP2B1&2, and polymeric
      immunoglobulin receptor mRNAs in male Fischer 344 rats.
AB  - Aging perturbs the expression of many liver proteins, but the mechanisms remain
      unresolved. Expression of hepatic NADPH cytochrome P450 reductase, phenobarbital
      induced CYP2B1&2, and the polymeric immunoglobulin receptor (pIgR) decline as a
      function of aging. We examined the effect of aging on the expression of the mRNA
      transcripts of these proteins, as well as those of alpha 2u-globulin and beta
      actin in male F344 rats. Despite age-related losses in the expression of P450
      reductase and plasma membrane-bound pIgR in the rat liver (approximately 30-50%),
      aging is is accompanied by 1) no change and 2) a modest decline (< 20%) in their
      respective mRNA steady state levels. On the other hand, the expression of
      phenobarbital-induced microsomal CYP2B1&2 and the steady state level of its mRNA
      exhibit parallel age-dependent shifts. The mRNA transcript for alpha 2u-globulin
      declines between maturity and old age, whereas the beta-actin mRNA level remains
      unchanged. These preliminary data are consistent with previous studies which
      suggest that aging may perturb hepatic CYP2B1&2 and alpha 2u-globulin at the
      transcriptional level, whereas changes in the expression of P450 reductase and
      pIgR may reflect posttranscriptional modifications.

PMID- 7517892
TI  - Inhibition by calmodulin antagonists of the neurogenic relaxation in cerebral
      arteries.
AB  - The present study was aimed to determine the effect of calmodulin inhibitors on
      the relaxant response of isolated dog and monkey cerebral arteries to vasodilator
      nerve stimulation, which is hypothesized to be mediated by nitric oxide (NO) from
      nerve endings. The relaxations caused by nerve stimulation by electrical pulses
      in endothelium-denuded arteries were attenuated by treatment with calmidazolium
      and W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide hydrochloride) and
      were abolished by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, and
      tetrodotoxin. The calmodulin inhibitors also attenuated the relaxations caused by
      nicotine and substance P, which were endothelium-independent and -dependent,
      respectively, but did not influence the relaxant response to NO. It is concluded
      that calmodulin is required for activation of the NO synthase present in the
      vasodilator nerve as well as that in the endothelium.

PMID- 7517897
TI  - VCAM-1 expression on reactive and tumour astrocytes.
AB  - In our studies we used a monoclonal antibody recognizing the vascular adhesion
      molecule (VCAM-1). Tissue samples were collected at autopsy from human brain
      infarcts and from brain tumours, removed during surgical procedure (Neurological
      and Neurosurgical Clinic, Cracow). A novel, unexpected finding were VCAM-1
      positive fibrous astrocytes in the stroke tissue, and astrocyte-like cells in the
      tumours. No staining was obtained either in the contralateral hemisphere or
      outside of ischemic areas. Likewise, no positive staining of cells was seen
      outside the tumour tissue. The above findings, taken together, strongly support
      the concept that astrocytes take part in the immune defense during various
      pathological processes in the human brain.

PMID- 7517896
TI  - Functional expression of 2-amino-4-phosphonobutyrate (APB) receptors in Xenopus
      laevis oocytes by injection of poly(A)+ RNA from quail brain.
AB  - The glutamate analogue 2-amino-4-phosphonobutyrate (APB) is known to activate a
      subtype of metabotropic glutamate receptor in the central nervous system,
      including the retina. In the present study, APB receptors were studied using the
      Xenopus oocyte expression system. No endogenous APB sensitivity was detected in
      control oocytes. In contrast, microinjection of mRNA, extracted from quail brain,
      into Xenopus oocytes resulted in the functional expression of APB receptors after
      3-5 days incubation. Application of 50 microM-1 mM APB to injected oocytes
      voltage clamped at a holding potential of -60 mV produced a sustained outward
      current which was associated with a significant decrease in membrane conductance;
      the reversal potential was around -11 mV. The response to APB was dose-dependent
      and non-desensitizing. This is the first demonstration of the expression of a
      conductance-decreasing receptor mechanism in Xenopus oocytes.

PMID- 7517898
TI  - Modulation of angiogenesis in vitro by laminin-entactin complex.
AB  - Laminin is a cross-shaped glycoprotein whose inner cross-region binds to the
      glycoprotein entactin (nidogen) forming a stable complex extractable from
      basement membrane matrices with chelating agents. In this study we evaluated the
      effect of the laminin-entactin complex on angiogenesis in serum-free collagen gel
      culture of rat aorta. Laminin-entactin stimulated or inhibited angiogenesis
      depending on its concentration in the gel. Stimulatory concentrations of laminin
      entactin (30 to 300 micrograms/ml) promoted an increase in the number and length
      of microvessels. A similar effect was observed with purified laminin. Elongation
      of microvessels was also obtained with the laminin fragments E1' and E8 and with
      entactin, all of which have binding sites for endothelial cells. By contrast the
      E4 fragment of laminin, which has no cellular binding sites, failed to promote
      microvascular elongation. Inhibitory concentrations of laminin-entactin (3000
      micrograms/ml) allowed formation of only a few stubby endothelial sprouts.
      Laminin-entactin promoted dose-dependent stabilization of microvessels preventing
      their regression. Microvessels stabilized by laminin-entactin were surrounded by
      thick patches of basement membrane-like material, whereas untreated microvessels
      prone to regression had a highly attenuated basement membrane. The angiogenic
      effect of laminin-entactin was enhanced by exogenous bFGF. However, bFGF was
      unable to stimulate angiogenesis over control values when incorporated in gels
      containing a high concentration of laminin-entactin. Our results indicate that
      laminin and its supramolecular complex laminin-entactin play an important
      modulatory role in angiogenesis. The dose-dependent effects of the laminin
      entactin complex suggest that the basement membrane is a dynamic regulator of
      angiogenesis whose function varies depending on the concentration of its
      molecular components.

PMID- 7517899
TI  - Human uterine cervical epithelial cells grown on permeable support--a new model
      for the study of differentiation.
AB  - The purpose of the present study was to establish culture conditions for human
      uterine cervical epithelial cells on permeable support and to determine how it
      affects cervical cell differentiation. Human ectocervical epithelial cells
      (hECE), HPV-16 immortalized hECE cells (ECE16-1) and Caski cells were grown on
      collagen-coated filters. Culture conditions, density of cells in culture and
      expression of epithelial and cervical-cell phenotypic markers were determined and
      compared in cells grown on filter and on solid support. Compared with the latter,
      cultures on filter had a higher cell density, hECE cells stratified to 5-12 cell
      layers compared to 1-3 on solid support, and cells of all three types expressed
      intercellular tight junctions. The cytokeratin profiles revealed differences
      between the three cell types as well as differences within the same cell species
      when grown on filter, compared to solid support. Of particular importance was the
      finding of a higher expression of K-13 in hECE grown on filter compared to solid
      support; K-13 is a marker of ectocervical cell differentiation. The cytokeratin
      profiles of the cultured hECE, ECE16-1 and Caski cells resembled those of
      ectocervical, squamous metaplastic and endocervical epithelia, respectively. hECE
      and ECE16-1 expressed involucrin protein, the level of which in both was higher
      in cells grown on filter compared to solid support. Polarization of the cultures
      was determined by morphology (stratification of hECE cells, expression of
      pseudomicrovilli in the apical cell membrane), selective apical vs. basolateral
      secretion of [35S]methionine- and [35S]cysteine-, [3H]fucose- and
      [14C]glucosamine-labeled molecules, and positive short-circuit current (Isc)
      under voltage-clamp conditions. Confluency of the cultures was determined by
      measuring transepithelial unidirectional fluxes of inert molecules with different
      molecular weights (MWs) through the paracellular pathway, and by measuring
      transepithelial conductance. The results indicated transepithelial permeability
      of 7-22.10(-6) cm.sec-1, which was 5-100 fold smaller compared to blank inserts,
      with a cut-off MW of 40-70 kDa for hECE and Caski cells. Transepithelial
      conductance ranged 18.5 to 51.5 mS.cm-2, indicating a leaky but confluent
      epithelia. Collectively the results indicate the epithelial nature of the cells
      and their improved differentiation when grown on filter support; hECE is a model
      for ectocervical epithelium while ECE16-1 and Caski express phenotypic
      characteristics of squamous metaplastic cervical epithelium and endocervical
      epithelium respectively.

PMID- 7517902
TI  - Effect of arabinosylcytosine derivative cyclocytidine on hepatal functions in
      rats and on Zajdela hepatoma.
AB  - 1. The effectivity of the arabinosylcytosine (araC) derivative, cyclocytidine
      (cC), against Zajdela hepatoma was evaluated. It was established that the cC
      effect was dose-dependent. 2. Zajdela hepatoma-bearing rats, given a single dose
      of 500 mg of cC per kg of body weight, showed an increased life span of 48 and
      39%. 3. cC significantly decreased the number of Zajdela hepatoma cells in
      ascitic fluid and affected the cytochrome content in hepatal mitochondria. 4. The
      overall cC effect on the hepatal function of normal and hepatectomized liver was
      marginal, thus making this araC derivative an interesting candidate for further
      evaluation of its effectivity against non-hematological tumors.

PMID- 7517900
TI  - Fetal rat glandular stomach epithelial cells differentiate into surface mucous
      cells which express cathepsin E in the absence of mesenchymal cells in primary
      culture.
AB  - It is well established that the differentiation of glandular stomach epithelial
      cells is affected by many factors including epithelial-mesenchymal interactions.
      To clarify the control mechanism of their differentiation, we developed a primary
      culture system for fetal rat glandular stomach epithelial cells, and examined
      their differentiation in the absence of mesenchyme. Pure glandular stomach
      epithelial tissues obtained from 16.5-day fetal rats proliferated rapidly,
      increasing their number about 20 times in the first 7 days. The epithelial nature
      of the cells was confirmed by the presence of cytokeratin in the cells. Glandular
      stomach epithelial cells formed simple cuboidal/squamous epithelia with many
      mucous granules in their cytoplasm, and exhibited epithelial polarity with
      microvilli on the luminal surface, basal lamina-like material on the basal
      surface, and junctional complexes in the apical region. Biochemical analysis
      showed that the cells expressed acid protease activity in culture. Previous
      studies showed that glandular stomach epithelial cells specifically expressed two
      types of acid proteases: pepsinogens in chief and mucous neck cells, and
      cathepsin E in surface mucous cells. Immunohistochemical studies using specific
      antibodies showed that the cultured cells expressed cathepsin E but not
      pepsinogens, and the result was confirmed by zymogram and Western blotting
      analysis. We thus concluded that fetal rat glandular stomach epithelial cells
      differentiated into surface mucous cells that expressed cathepsin E in primary
      culture in the absence of mesenchyme.

PMID- 7517901
TI  - Sialogogic activities of SNI-2011 compared with those of pilocarpine and McN-A
      343 in rat salivary glands: identification of a potential therapeutic agent for
      treatment of Sjorgen's syndrome.
AB  - 1. We examined the sialogogic activities in rat major salivary glands of SNI
      2011, in comparison with those of pilocarpine and McN-A-343, and we characterized
      the subtypes of muscarine receptors that are involved in the sialogogic responses
      to SNI-2011 and McN-A-343. 2. SNI-2011 at doses ranging from 1 to 10 mg/kg (i.v.)
      increased the secretion of saliva in a dose-dependent manner. The dose-response
      curves for SNI-2011 were approximately parallel to curves for pilocarpine but the
      potency of SNI-2011 was about 25-fold lower than that of pilocarpine. 3. The
      total volume of saliva secreted in response to McN-A-343 was very much less than
      that secreted in response to SNI-2011. 4. The salivation induced by SNI-2011 and
      by McN-A-343 was inhibited by various antagonists with the following rank order
      of potency: 4-DAMP >> pirenzepine >> AF-DX 116. 5. Our results suggest that the
      sialogogic effects of SNI-2011 and McN-A-343 are mediated by direct stimulation
      of M3 receptors in salivary glands and that SNI-2011 may prove useful in the
      management of xerostomia in patients with Sjogren's syndrome.

PMID- 7517903
TI  - A regional difference of the effect of tachykinin on cholinergic response evoked
      by electrical field stimulation in the rabbit airway.
AB  - 1. Experiments were designed to determine whether regional differences exist in
      the effects of phosphoramidon (a metalloprotease inhibitor) and [D-Arg,1D-Pro,2 D
      Trp,7,9Leu,11]-substance P (a tachykinin antagonist: rpwwL-SP) on contractile
      responses to electrical field stimulation (EFS) in rabbit airways. 2. EFS
      contractions were potentiated by phosphoramidon and were attenuated by rpwwL
      substance P at low frequencies (less than 10 Hz). 3. Potentiating effect of
      phosphoramidon was more pronounced in distal bronchus than trachea and was
      proportional to total proteinase activity. 4. The rank order of inhibitory effect
      of rpwwL-SP was: trachea > proximal bronchus > distal bronchus, and inverse
      relationship was observed between the drug's inhibitory effect of drug and total
      proteinase activity in three different regions. 5. Good correlation was observed
      between total proteinase activity and pD2 value of neurokinin A in each airway
      region. 6. In conclusion, tachykinin modulates acetylcholine release in the
      contractile response to EFS at low frequencies (less than 10 Hz), and regional
      differences in the effects of the inhibitor and the antagonist on EFS-evoked
      contractions in the rabbit airway were suggested to be due to heterogenous
      distribution of the metalloprotease which metabolized tachykinins.

PMID- 7517906
TI  - Transcriptional analysis and heterologous expression of the gene encoding beta
      lactamase inhibitor protein (BLIP) from Streptomyces clavuligerus.
AB  - Transcription of bli, the gene encoding beta-lactamase (Bla) inhibitor protein
      (BLIP) of Streptomyces clavuligerus, was analyzed by promoter-probe studies,
      Northern hybridization and high-resolution S1 nuclease mapping. The 1-kb SalI DNA
      fragment immediately upstream from the bli open reading frame (ORF) showed
      promoter activity when tested using the xylE-based promoter-probe vector,
      pIJ4083. The promoter activity was approx. 36-fold higher in S. clavuligerus than
      in S. lividans. Northern hybridization analysis of S. clavuligerus RNA revealed
      that bli was expressed as a 0.7-kb monocistronic transcript. High-resolution S1
      nuclease mapping identified the transcription start point as an A residue 47 bp
      upstream from the bli start codon. When the bli ORF, along with 111 bp of
      upstream sequence including the promoter, was introduced into S. lividans, the
      transformants produced BLIP, but in amounts approx. 12-fold lower than that
      produced by S. clavuligerus. Involvement of some additional regulatory element
      that is present in S. clavuligerus, but absent in S. lividans, could explain the
      difference in the promoter activities and therefore the difference in the overall
      expression of bli in the two hosts.

PMID- 7517907
TI  - Cloning vectors for the synthesis of epitope-tagged, truncated and chimeric
      proteins in Saccharomyces cerevisiae.
AB  - A series of cloning vectors, designated YCpIF, was constructed to facilitate the
      conditional synthesis of epitope-tagged, truncated and chimeric proteins in
      Saccharomyces cerevisiae. These vectors contain a translation start codon
      upstream from a multiple cloning site (MCS) in each of the three reading frames.
      Protein synthesis is under the control of the GAL1 promoter, which drives
      transcription when cells are grown on galactose-containing medium, but not when
      they are grown on glucose-containing medium. Different versions of the vectors
      contain four different commonly used selectable markers. In addition, YCpIF15,
      YCpIF16 and YCpIF17 contain a sequence encoding an epitope from influenza virus
      hemagglutinin upstream from the MCS. These vectors facilitate the addition of
      this epitope tag to the N terminus of any protein. The epitope is recognized by a
      commercially available monoclonal antibody.

PMID- 7517908
TI  - [Potentiating effect of hexachlorane and sodium nitrite on rat erythrocytes].
AB  - Combined effect of hexachloran (HCh) and sodium nitrite (SN) on rats was studied.
      HCh potentiated SN effect on blood methemoglobin level.

PMID- 7517904
TI  - The role of calcium and alpha-adrenoceptors in contractile response of chick
      expansor secundariorum muscle to field stimulation.
AB  - 1. The effects of some alpha-adrenergic agonists and antagonists on electrically
      evoked contractions and tension of chick expansor secundariorum muscle (ESM), and
      dependence of these events on extracellular calcium was investigated. 2. Both
      train and continuous electrical stimulation can produce regular contractions in
      preparations obtained from 40-60 day old chicks. 3. Clonidine had a biphasic
      action on the contractions produced by train electrical stimulation. In
      concentrations ranging from 10(-8) to 3 x 10(-7) M, clonidine decreased the
      contraction amplitude, but in higher concentrations, it caused an increase in
      both the muscle tension and the contraction amplitude. These effects were
      reversed by application of yohimbine although yohimbine by itself had no effect
      on the contractions. 4. Introduction of calcium free isotonic high potassium
      medium decreased muscle tone which was followed by further dose-dependent
      increase in tension, along with the addition of cumulative doses of CaCl2 (ED50 =
      2.8 x 10(-3) M). 5. Nifedipine reduced the amplitude of ESM contractions produced
      by continuous electrical stimulation in a dose dependent manner (IC50 = 6.7 x 10(
      7) M). 6. Methoxamine induced a completely dose dependent increase in muscle
      tension which was dependent on extracellular calcium and was inhibited by
      nifedipine. In the presence of 10(-8) M nifedipine, ED50 of methoxamine
      stimulatory effect increased from the control value of 2.2 x 10(-7) to 8.4 x 10(
      7) M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517909
TI  - [Hygienic evaluation of photochemical transformation of automobile exhaust fumes
      as effected by ozone].
AB  - Ozonizing of exhausted motor transport gases increases their toxicity. The most
      dangerous of formed substances are: nonanal, acetophenon, octanal, benzaldehyde,
      heptanal, decanal, 2-butanone.

PMID- 7517905
TI  - Antigenic diversity within a family of M proteins from group A streptococci:
      evidence for the role of frameshift and compensatory mutations.
AB  - The genes (emm) encoding M proteins, from isolates of group-A streptococci (GAS)
      serotyped as M52, M53, M80 and M nontypeable (MNT; serologically related to M53
      and M80), were examined. Characterization of emm from these GAS revealed some
      discrepancies with serotyping, illustrating the difficulty in serotype
      determination when cross-reactions occur. DNA sequences corresponding to the N
      terminal region of M proteins from the isolates showed considerable similarity
      both in the hypervariable region and the repeat regions. We propose that these
      serotypes form a family of closely related M types. Frameshift mutations in the
      hypervariable region followed by a corrective (compensatory) frameshift were
      observed. This may be an effective mechanism for generating antigenic diversity
      in the M protein.

PMID- 7517910
TI  - Photosensitization with anticancer agents 19. EPR studies of photodynamic action
      of calphostin C: formation of semiquinone radical and activated oxygen on
      illumination with visible light.
AB  - When calphostin C was illuminated with visible light, the semiquinone radical,
      singlet oxygen, and superoxide anion radical were detected. The formation of the
      semiquinone radical and activated oxygen species and the transformations and
      competitions between them depend upon the quinone and oxygen concentrations, time
      and intensity of illumination, and the nature of the substrate. In anaerobic
      solution, the semiquinone radical was predominantly photoproduced via the self
      electron transfer between the excited and ground species. In aerobic solution,
      singlet oxygen is the principal product in the photosensitization of calphostin
      C. In addition to singlet oxygen, superoxide anion radical is also generated by
      the quinones upon illumination in aerobic solution, but to a lesser extent than
      singlet oxygen. The superoxide anion is produced via the reduction of oxygen by
      the semiquinone radical, and this process is significantly enhanced by the
      presence of electron donors.

PMID- 7517911
TI  - A comparative immunohistochemical study of uterine smooth muscle neoplasms with
      emphasis on the epithelioid variant.
AB  - We evaluated the immunophenotypes of 22 spindled and 36 epithelioid uterine
      smooth muscle neoplasms (SMNs) and 16 extrauterine nongastrointestinal spindled
      smooth-muscle neoplasms for various markers. The epithelioid neoplasms were
      subdivided into two histological groups designated true and intermediate, the
      former showing typical epithelioid features and the latter showing epithelioid
      features that could be explained by cross-sectioning of blunt spindled cells.
      Desmin, muscle-specific actin, and smooth muscle actin were equally sensitive in
      detecting muscle differentiation in all these neoplasms. The true epithelioid
      variants were more frequently keratin positive but less frequently positive for
      vimentin, CD34 or the muscle markers, compared with their spindled counterparts.
      The intermediate epithelioid variants more closely resembled the spindled
      neoplasms in their immunostaining for muscle markers, vimentin, and CD34 but like
      the true epithelioid variants were relatively frequently positive for keratin.
      CD34 was positive in 36% of the spindled and 6% of the true epithelioid uterine
      SMNs, in most cases faintly. Antikeratin AE1 was positive more frequently than
      CAM5.2, with 18% of the spindled and 35% of the true epithelioid neoplasms being
      AE1 positive. The immunophenotype of uterine SMNs, including the epithelioid
      variant, permits their distinction from carcinomas based on their frequent
      reactivity for muscle markers in spite of their high rate of keratin positivity.
      They show sufficient overlap in immunoreactivity with endometrial stromal
      sarcomas to preclude definitive differentiation from them on immunohistochemical
      features alone.

PMID- 7517912
TI  - Solid cell nests of the thyroid: light microscopy and immunohistochemical
      profile.
AB  - The morphological, histochemical, and immunohistochemical findings of seven cases
      of solid cell nests (SCNs) of the thyroid are described. Light microscopy showed
      two cell types forming the SCNs, which we refer to as "main cells" and "C cells."
      In all cases "mixed thyroid follicles" (a unique structure lined by follicular
      epithelium and epidermoidlike cells) were observed in which the histochemical
      study confirmed the presence of intraluminal acid mucins. Adult adipose tissue
      and cartilage were found in one case and foci of cartilage were observed in
      another case in association with the SCN. Immunohistochemical studies showed
      positivity of "main cells" for carcinoembryonic antigen (CEA), high- and low
      molecular weight keratins, neurotensin, and somatostatin. "C cells" were positive
      for calcitonin, calcitonin gene-related peptide (CGRP), and chromogranin. The two
      cell types in SCNs were consistently negative for thyroglobulin. Neuron-specific
      enolase (NSE)-positive cells were found in the vicinity of the SCN. The unusual
      association of adipose tissue and cartilage as well as the results of the
      extended immunohistochemical study in this series provides further support to the
      belief that SCNs and "mixed thyroid follicles" represent remnants of the
      ultimobranchial body and should be considered normal components of the thyroid
      gland.

PMID- 7517913
TI  - A generalized ionic model of the neuronal membrane electrical activity.
AB  - A new ionic model of the neuronal-membrane electrical activity has been
      developed. The proposed model generalizes those usually quoted in the literature,
      taking into account the significant ionic currents, the temperature dependence of
      the electrical parameters, and the stochastic synaptic inputs. The model allows
      us to simulate both the membrane firing activity, as a function of the
      temperature, and the membrane resistance behavior, as a function of temperature
      and of intracellular calcium concentration. The I-V nonlinear characteristic,
      together with histograms and correlograms of the time intervals between spikes,
      have been numerically reproduced. Various comparisons we have carried out with
      available experimental data show a good theoretical-experimental agreement.

PMID- 7517914
TI  - Mutants of cultured mouse cells deficient in Ly-2 antigen.

PMID- 7517916
TI  - Flow cytometric evaluation of the acrosome reaction of human spermatozoa: a new
      method using a photoactivated supravital stain.
AB  - A flow cytometric assay using a double-stain method for the measurement of the
      acrosome reaction of human spermatozoa is described. The use of a stable
      photoactivated stain, ethidium monoazide, allowed evaluation of the viability of
      spermatozoa. This stain was more stable in fixed samples than propidium iodide,
      which is not bound covalently to DNA and is therefore removed readily during the
      washing procedure. The permeabilized acrosome was labelled with Pisum sativum
      agglutinin conjugated with fluoroisothiocyanate. Since this lectin binds to the
      acrosome and acrosomal contents, a decrease in the fluorescence intensity allows
      the cytometric evaluation of the acrosome reaction. Microscopic analysis and flow
      cytometric analysis were well correlated and cell sorting was performed to ensure
      the homogeneity of each different subpopulation encountered.

PMID- 7517915
TI  - HLA-B73: an atypical HLA-B molecule carrying a Bw6-epitope motif variant and a B
      pocket identical to HLA-B27.

PMID- 7517917
TI  - Expression of the c-kit protein product in carcinoma-in-situ and invasive
      testicular germ cell tumours.
AB  - Carcinoma-in-situ of the testis (CIS) is the precursor of invasive germ cell
      tumours. It is believed that CIS cells may originate from early fetal gonocytes.
      Recently, the proto-oncogene c-kit has been implicated as crucial for the
      development and migration of primordial germ cells. In this study, CIS and
      overtly invasive human male germ cell tumours were analysed immunohistochemically
      for expression of the c-kit proto-oncogene protein product. Testicular tissue
      samples from 36 patients with various types of testicular germ cell neoplasia and
      19 control specimens were stained using an indirect immunoperoxidase method. High
      expression of c-kit was found in almost all cases of CIS, both when the lesion
      was the only pathology, and when CIS was adjacent to invasive tumours. The Kit
      staining was retained in seminomas with variable intensity; the majority of cells
      in tumour mass exhibited c-kit expression in 61% of the samples while focal
      expression was observed in 39% of the samples studied. No expression of c-kit was
      detected in non-seminomas or in normal testicular germ cells. High expression of
      the proto-oncogene in CIS cells supports the hypothesis of their origin from
      primordial germ cells. In addition, we propose that the c-kit protein product is
      a new marker for carcinoma-in-situ of the testis.

PMID- 7517918
TI  - Biased utilization of immunoglobulin variable region heavy- and light-chain genes
      by the malignant CD5- B lymphocytes from patients with Burkitt's lymphoma.
AB  - Twenty-six established Burkitt's lymphoma (BL) cell lines from endemic or
      sporadic groups of patients were examined for the expression of cross-reactive
      idiotypes (CRI) associated with VHI, VHIII, VHIV, VHVI, VKIIIa and VKIIIb heavy-
      and light-chain gene products, using a panel of anti-CRI and anti-subgroup
      monoclonal antibodies (MAbs). Membrane, cytoplasmic and secreted immunoglobulins
      (Ig) were analysed by immunofluorescence, immunoperoxidase and ELISA
      respectively. While 35% of the lines expressed either of the VHIV-associated CRI,
      recognised by the MAbs 9G4 or LCI, none expressed the other VH-associated CRI
      included in our study. Of the kappa light chain expressing BL lines 54% and 46%
      belonged to the VKIII subgroup and VKIIIb sub-subgroups respectively. None,
      however, was found to express the VKIIIa or VKIIIb-associated CRI, recognised by
      the 6B6.6 and 17-109 MAbs. A significant association has been observed between
      the expression of the VHIV-associated CRI and the VKIII subgroup within the BL
      lines derived from the sporadic group of patients as compared with their endemic
      counterparts. Our results suggest that the expressed repertoire of Ig variable
      region genes within the malignant B lymphocytes of BL is not random and that a
      highly selective mechanism(s) may operate on this subset of B lymphocytes, as
      evidenced by the expression of the VH and VK gene products.

PMID- 7517920
TI  - Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1
      (MCP-1) in vivo and in vitro.
AB  - Expression of the monocyte chemoattractant protein-1 (MCP-1) was examined in
      human central nervous system tumours (glioblastomas and astrocytomas) and normal
      human brain. Northern blot analysis demonstrated constitutive expression of MCP-1
      mRNA in 6 of 12 glioblastoma cell lines. Expression could be stimulated by
      interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha in all cell lines
      tested. Immunoprecipitation demonstrated secretion of both isoforms, MCP-1 alpha
      and -beta, of the MCP-1 protein. Reverse-transcription polymerase chain reaction
      and Northern blot analysis on tissues demonstrated MCP-1 mRNA expression in 17 of
      17 glioblastomas, 3 of 6 anaplastic astrocytomas and 6 of 6 low-grade
      astrocytomas, as well as in fetal brain but not in normal adult brain. In situ
      hybridization on 2 glioblastomas and 1 low-grade astrocytoma indicates that
      neoplastic astrocytes and endothelial cells express MCP-1 mRNA in vivo. Moreover,
      tumour cyst fluids of glioblastomas and astrocytomas were able to induce monocyte
      chemoattraction in an in vitro assay. This chemotactic activity was specifically
      neutralized by anti-MCP-1 antibodies in 9 of 10 samples, further demonstrating
      the production of bioactive MCP-1 in vivo and supporting an important role for
      this factor in the infiltration of monocytes/macrophages into tumour tissue.

PMID- 7517919
TI  - Stimulation of angiogenesis as an explanation of Matrigel-enhanced
      tumorigenicity.
AB  - Matrigel, a reconstituted extract of basement membrane, enhances the growth of
      different human cancer cell lines when transplanted into nude mice. Here that
      stimulation was confirmed in the BALB/c murine mammary-tumor cell line M3MC, as
      well as in human colon (SW948) and mammary (MDA-MB-468) carcinoma cell lines
      transplanted in nude and SCID mice, respectively. Subcutaneous and intra-mammary
      fat-pad inoculations of Matrigel alone generated an angiogenic response which was
      macroscopically evident by day 9. Histological analysis of the local host
      reaction occurring at the site of injection revealed an early peripheral
      fibroblast response, followed by mononuclear cell infiltration, solid and hollow
      fibroblast cords projections from the edge to the center of the Matrigel plug,
      and finally capillary ingrowths. Conditioned media obtained from the gels
      generated in vivo, acted as very strong chemoattractants for mouse lung capillary
      endothelial cells, stimulating their motility between 38 and 82 times with
      respect to the control. Our results suggest an important role of host cells
      recruited by Matrigel, which could favor angiogenesis of the area and thus
      facilitate the growth of tumor cells co-inoculated with the basement membrane
      extract.

PMID- 7517921
TI  - Scattered micrometastases visualized at the single-cell level: detection and re
      isolation of lacZ-labeled metastasized lymphoma cells.
AB  - To study metastasis at the single-cell level we transduced highly metastatic ESb
      lymphoma cells with a retroviral expression vector containing the lacZ (bacterial
      beta-galactosidase) gene. This allowed single ESb-lacZ tumor cells to be detected
      in infiltrated target organs by means of X-Gal staining. Despite expression of
      the lacZ gene, the tumor cells were still tumorigenic, highly metastatic,
      unchanged in phenotype and therefore comparable to parental ESb cells. After
      spontaneous metastasis, whole-organ staining revealed metastatic foci at the
      surface of the liver. In histological liver sections, metastatic clusters and
      single dispersed tumor cells could be detected. In contrast to whole-organ
      staining, histological examination revealed scattered distribution of tumor cells
      throughout the organ, which was not evident with parental ESb cells. In addition,
      clusters with diffuse or dense (focal) appearance were found, in correlation with
      the whole-organ staining. Expression of the foreign lacZ gene allowed the
      metastatic spread of tumor cells to liver and spleen to be quantified
      approximately by FACS analysis. Furthermore, it was shown that the newly
      expressed beta-gal was expressed not only intercellularly but also at the cell
      surface. There it could be recognized by MAbs and cytotoxic T-cells (CTL). beta
      gal did not affect CTL recognition of the ESb tumor-associated antigen. In
      conclusion, lacZ could be used as a genetic marker for a highly metastatic
      lymphoma, to define scattered metastatic spread in the liver at the single-cell
      level and to quantify the tumor load by FACS analysis.

PMID- 7517924
TI  - Substance P: correlation of CSF and plasma levels.
AB  - OBJECTIVE: To determine the correlation between cerebrospinal fluid and plasma
      concentrations of substance P. PATIENTS: 37 patients undergoing lumbar puncture
      for various diagnostic purposes. MEASUREMENTS: Samples of cerebrospinal fluid and
      blood were obtained at the same visit. Substance P was measured by
      radioimmunoassay technique. At least 4 separate measurements were conducted on
      each sample to insure accuracy. RESULTS: The mean plasma SP level was 1.195 (+/-
      1.1). The mean cerebrospinal fluid substance P level was 1.075 (+/- .07). There
      was a statistically significant positive correlation between substance P level in
      the plasma and cerebrospinal fluid. The Pearson correlation coefficient was 0.656
      (P < .0001) and the Spearman correlation coefficient was 0.698 (P < .0001).
      CONCLUSIONS: Plasma substance P levels closely correlate with cerebrospinal fluid
      substance P levels. This will simplify the measurement of substance P in the
      evaluation of therapeutic agents for headache.

PMID- 7517922
TI  - In vivo evidence of the role of alpha 4 beta 1-VCAM-1 interaction in sarcoma, but
      not in carcinoma extravasation.
AB  - Tumor-cell invasion can occur via either lymphatics or blood vessels. When in the
      blood circulation, tumor cells have to adhere to endothelium lining the blood
      vessels before they can extravasate. Several families of adhesion molecules have
      been recognized: selectins and their oligosaccharide-containing ligands and
      integrins and their counter-receptors belonging to the immunoglobulin
      superfamily. Besides their essential role in leukocyte extravasation, these
      adhesion molecules have been proposed by vitro experiments to be involved in
      tumor-cell invasion by facilitating the adhesion of malignant cells to
      endothelium leading to extravasation and metastasis. We have previously shown
      that, in vitro, several sarcoma cell lines adhere strongly to cultured
      endothelial cells via alpha 4 beta 1-VCAM-1 interaction. Here we show that
      sarcoma cells, especially in the metastatic lesions, were strongly alpha 4 beta 1
      positive but did not express alpha 4 beta 7, which is another receptor for VCAM
      I. Furthermore, we demonstrate that the capillary endothelium within metastatic
      sarcoma lesions reacted strongly with anti-VCAM-I antibody and very often the
      alpha 4 beta 1-expressing sarcoma cells were localized in the close vicinity of
      VCAM-I-expressing vessels. As control material we analyzed carcinoma specimens,
      but could not detect any alpha 4-integrin expression on malignant cells even
      though the endothelial cells were often VCAM-I positive. These results suggest
      that carcinomas do not use alpha 4 beta 1-VCAM-I in extravasation and, taken
      together, provide circumstantial evidence that in vitro findings of alpha 4 beta1
      VCAM-I-dependent sarcoma cell adhesion to endothelium can be extended to in vivo
      situations.

PMID- 7517925
TI  - Persistent post-dural-puncture headache treated with epidural infusion of
      dextran.
AB  - A retrospective review was done on medical records of 13 patients with persistent
      post-dural-puncture headaches after one or more epidural blood patches. Headache
      occurred in nine patients with post-laminectomy syndrome after "wet taps" while
      performing epidural blocks. In two patients post-dural-puncture headache appeared
      after long term implanted intrathecal catheters were removed. In two other cases
      headache developed after spinal anesthesia. Treatment included bed rest,
      intravenous hydration and at least one epidural blood patch; three patients were
      given 60 milliliters of epidural saline, without success. Eight epidural
      catheters were inserted through the lumbar access and five through the caudal
      approach. Initially, a bolus of 20 milliliters of dextran-40 was given followed
      by an infusion of 3 mL/hr, until 12 hours after the head pain and any other
      related symptoms subsided. In all patients the headache disappeared within 20
      hours after initiating therapy (9.55 mean hours, SD +/- 0.79). In five patients
      headache ceased in less than five hours. Nausea and photo-phobia subsided
      earlier. Patients with post-dural-puncture headache resistant to other
      treatments, including at least one epidural blood patch, were successfully
      treated by a bolus followed by continuous epidural infusion of dextran-40.

PMID- 7517926
TI  - Polychromatic staining of epoxy semithin sections: a new and simple method.
AB  - A simple, rapid method is described for the polychromatic coloration of semithin
      sections, which is applicable to material routinely processed for transmission
      electron microscopy. Material fixed with a glutaraldehyde-paraformaldehyde
      mixture and postfixed in osmium tetroxide with or without potassium ferrocyanide
      and embedded in different types of resin (Durkupan-ACM, Spurr resin, Taab resin)
      can be used. Constant and homogenous results are obtained with this technique,
      the staining procedure being achieved at room temperature in no more than 10 min.
      Sections of 0.5-1 microns in thickness are oxidised and bleached. After washing,
      sections are stained in two steps with carbol methylene blue/carbol gentian
      violet solution and pararosaniline solution. Using the method described in this
      paper, a polychromatic coloration of the different cells and tissues was obtained
      (epithelial cells in various shades of blue-violet, connective tissue and elastic
      laminae of blood vessels in pink or red, etc.). This procedure provides greater
      contrast between cytoplasm and nuclei, and among the different types of cells and
      tissues than is seen with toluidine blue, which is very useful for observation
      and photography of semithin sections. Polychromatic methods found in the
      literature are normally complex and require a lengthy staining time or cannot be
      applied on material routinely processed for transmission electron microscopy. Our
      method is simple, rapid and can be used on any type of material routinely
      processed for transmission electron microscopy and embedded in epoxy resins.

PMID- 7517928
TI  - Iodoplatinate visualization of phospholipids in rat incisor predentine and
      dentine, compared with malachite green aldehyde.
AB  - The iodoplatinate (IP) reaction, a selective method for visualization of
      phospholipids, was applied to the predentine and dentine of rat incisors and
      compared with malachite green aldehyde (MG) fixation/staining. Spot tests
      indicated (1) that IP specifically stains phospholipids, but not amino acids,
      displaying as do phospholipids, quaternary ammonium groups; and (2)
      phosphatidylserine and sphingomyelin were also stained by MGA. Although this
      reagent is known to interact with phosphorus, phosphoproteins remained unstained.
      In the rat incisor, an IP-positive network including granules and thin filaments
      was seen in predentine in the inter-collagen spaces, in many cases closely
      associated with collagen fibres and their periodic striations. In dentine,
      positively stained needle-like structures were located along individual collagen
      fibres, or at the surface of groups of collagen fibres. This staining pattern was
      unchanged on sections of material pretreated with acetone, whereas the staining
      was abolished or markedly reduced when the samples were treated either with
      chloroform/methanol or phospholipase C prior to the IP reaction. Pretreatment of
      the samples with hyaluronidase promoted subsequent diffusion of the staining. A
      very similar staining pattern was observed with MGA, in accordance with earlier
      reports. The present findings validate the histochemical results reported
      previously on the distribution and potential role(s) of phospholipids in dentine
      biomineralization.

PMID- 7517923
TI  - 371 bladder calculi in a benign prostatic hyperplasia patient.
AB  - We describe a patient with 371 bladder calculi secondary to benign prostatic
      hyperplasia. To our knowledge this patient had one of the highest numbers of the
      bladder calculi reported.

PMID- 7517927
TI  - Colocalization of cytokeratin 18 and villin in type III alveolar cells (brush
      cells) of the rat lung.
AB  - Alveoli of the rat lung are lined by three different cell types, the flat type I
      cells and the cuboidal type II and type III cells. Type III cells differ from
      type II cells by the presence of an apical tuft of microvilli and the absence of
      lamellar type secretory granules. In the present study we show by double
      immunolabelling that type III cells of the rat lung can be identified at the
      light- and electron microscope level by antibodies against both cytokeratin 18
      and the actin-crosslinking protein villin. At the ultrastructural level,
      microvilli and their rootlets in the apical cytoplasm were labelled by the anti
      villin antibodies, whereas a monoclonal antibody against cytokeratin 18 (Ks18.04)
      labelled bundles of intermediate filaments. In conclusion, antibodies against
      villin and certain monoclonal antibodies specific for cytokeratin 18 can be used
      as tools for selective visualization of type III cells in the rat lung.

PMID- 7517929
TI  - Antibody against single-stranded DNA detects both programmed cell death and drug
      induced apoptosis.
AB  - Cyclophosphamide induced fragmented nuclei in mouse thymic epithelial cells.
      Agarose gel electrophoresis showed the fragmentation of the DNA extracted from
      mouse thymus exposed to cyclophosphamide. The cell death induced by
      cyclophosphamide was considered to be apoptotic. Polyclonal antibody against
      single-stranded DNA was used immunohistochemically to detect apoptotic cell death
      in thymic epithelial cells. This antibody also detected programmed cell death in
      the interdigital necrotic zone of the mouse limb plate on day 14 of gestation,
      and in the ganglion of the trigeminal nerve on day 13 of gestation. These results
      show that the antibody specific for single-stranded DNA detected both drug
      induced apoptosis and programmed cell death during embryogenesis.

PMID- 7517930
TI  - Heterogeneity in calbindin-D28k expression in oxytocin-containing magnocellular
      neurons of the rat hypothalamus.
AB  - We have used a double-labeling immunofluorescence method to examine whether
      oxytocin-containing magnocellular neurons possess a calcium-binding protein,
      calbindin-D28k, in the hypothalamus of the rat. In the supraoptic nucleus, most
      oxytocin-immunoreactive cells were also stained for calbindin-D28k. However, in
      the magnocellular part of the paraventricular nucleus nearly all oxytocin-labeled
      cells were devoid of calbindin-D28k. In the anterior commissural nucleus,
      approximately one-third of oxytocin-stained cells were also calbindin-D28k
      immunoreactive, but the other cells were negative for calbindin-D28k. This study
      indicates that there may be distinct chemical features between oxytocin
      containing magnocellular neurons of the supraoptic nucleus compared to those of
      the paraventricular nucleus.

PMID- 7517932
TI  - On the mechanism of the nitric oxide synthase-catalyzed conversion of N omega
      hydroxyl-L-arginine to citrulline and nitric oxide.
AB  - The mechanism of oxidation of N omega-hydroxyl-L-arginine (NHA) by the iron
      dioxygen complex in nitric oxide synthase (NOS) is still uncertain. The
      uncertainty has not been helped by a lack of precision in the notation used to
      describe the oxidation states and electrical charges on the iron and oxygen in
      some of the suggested mechanisms. These problems of notation are addressed, and,
      in addition, a cyclic voltammetric measurement of the oxidation potential of NHA,
      namely +0.10 +/- 0.04 V versus normal hydrogen electrode, is used to argue that
      the sometimes postulated oxidation of NHA by the iron-dioxygen complex to form an
      intermediate radical cation, NHA.+, is very unlikely for thermodynamic reasons.
      Instead, it is suggested that this oxidation occurs by a thermodynamically
      favored abstraction of the hydrogen atom from the > C = NOH moiety of NHA to form
      an intermediate iminoxyl radical, > C = NO(.). A subsequent nucleophilic attack
      by the iron-hydroperoxide species formed by this H-atom abstraction on the carbon
      atom of the iminoxyl radical moiety leads to the production of nitric oxide (NO)
      and citrulline.

PMID- 7517931
TI  - Analysis of overlapping T- and B-cell antigenic sites on rubella virus E1
      envelope protein. Influence of HLA-DR4 polymorphism on T-cell clonal recognition.
AB  - A CTL antigenic site located between residues 273 and 291 of the E1 envelope
      protein of RV was identified by 51Cr-release assays employing SPs. Two E1
      specific CTL clones were examined for immune recognition of RV wild-type and
      attenuated vaccine strains and recombinant E1 protein. The exact sequence (273
      284) recognized by both clones was delineated by using truncated and overlapping
      SPs covering these residues. The defined T-cell site overlapped almost completely
      with a virus neutralizing antibody-binding site previously identified with mouse
      monoclonal and human antibodies. A series of single aa-substituted SP analogues
      of E1(273-284) was used to define residues critical for T-cell recognition. Using
      EBV-BL displaying different HLA-DR haplotypes and -DR4 subtypes as targets to
      determine MHC class II restriction elements, immune recognition by both T-cell
      clones was shown to be associated with HLA-DR4. Three HLA-DR4 subtypes (DR4Dw13A,
      DR4Dw13B, and DR4KT2) sharing a common residue, glutamic acid at position 74 in
      their beta 1 chains, were able to present SP E1(273-284) to the T-cell clones.

PMID- 7517934
TI  - Nodulin 26, a nodule-specific symbiosome membrane protein from soybean, is an ion
      channel.
AB  - Nodulin 26 is an integral symbiosome membrane protein of nitrogen-fixing soybean
      nodules. Nodulin 26 is a member of a family of structurally homologous membrane
      proteins with diverse transport functions. Thus, it has been proposed to be
      involved in symbiosome membrane transport. Despite this claim, there has not been
      any evidence that nodulin 26 has a transport activity. In this study, nodulin 26
      was purified from soybean nodules by a non-denaturing protocol and was
      reconstituted into liposomes for channel studies in planar lipid bilayers.
      Nodulin 26 readily incorporated into bilayers, forming single channels with a
      maximum unitary conductance of 3.1 nanosiemens (nS) in a recording buffer of 20
      mM 3-(N-morpholino)propanesulfonate-NaOH, pH 7.4, 1 M KCl. Nodulin 26 also
      exhibited multiple, discreet lower conductance states ranging from 0.5 to 2.5 nS.
      Nodulin 26 channels were voltage-sensitive. The maximal 3.1-nS state was
      preferentially occupied at lower applied voltages, whereas the lower conductance
      states were more frequently occupied at higher voltage potentials. Nodulin 26
      channels transported both cations and anions, but showed a weak selectivity for
      anions. These results represent the first purification and functional
      characterization of the nodulin 26 channel and support a role for this protein in
      symbiosome membrane transport.

PMID- 7517933
TI  - Premature translation termination mutations are efficiently suppressed in a
      highly conserved region of yeast Ste6p, a member of the ATP-binding cassette
      (ABC) transporter family.
AB  - The requirements for efficient translation termination are incompletely
      understood. Since the local context surrounding stop codons can influence the
      efficiency of translation termination, premature termination codons introduced by
      random mutation may not always terminate at the optimal efficiencies expected of
      naturally occurring stop codons. To investigate whether this could result in
      physiologically significant levels of read through, we examined the suppression
      of premature translation termination mutations within a sequence motif of the
      yeast Ste6 protein (Ste6p) that is highly conserved among members of the ATP
      binding cassette (ABC) transporter family. The human cystic fibrosis
      transmembrane conductance regulator (CFTR), which is defective in individuals
      with the disease cystic fibrosis, is also a member of this protein family. The
      mutations examined in Ste6p were chosen because a premature termination codon at
      the corresponding residue of CFTR has previously been reported to cause less
      severe pulmonary involvement than some missense mutations, suggesting that low
      level suppression of this stop codon could be occurring. Our results indicate
      that these premature stop codons in Ste6p can be suppressed at frequencies as
      high as 10%. Characterization of this phenomenon using a beta-galactosidase read
      through assay system showed that a limited sequence context surrounding this site
      contained information that was sufficient to cause suppression of translation
      termination. Amino acid sequence analysis of the full-length translation products
      produced by read through of an amber codon demonstrated that termination
      suppression was mediated by near-cognate tRNA mispairing that resulted in the
      insertion of tyrosine, lysine, or tryptophan.

PMID- 7517935
TI  - OmpA protein of Escherichia coli outer membrane occurs in open and closed channel
      forms.
AB  - OmpA protein of Escherichia coli outer membrane can produce diffusion channels
      when reconstituted into proteoliposomes (Sugawara, E., and Nikaido, H. (1992) J.
      Biol. Chem. 267, 2507-2511). The pore size is similar to that of the classical E.
      coli porins OmpF and OmpC, but the penetration rates of small solutes through the
      OmpA channel are about 50 times slower than that through the OmpF channel. Here
      we examined the possibility that only a small fraction of the OmpA molecules
      produces open channels. Unilamellar proteoliposomes were made so that each
      vesicle contained only a small number of OmpA molecules. These vesicles,
      containing 0.3 M urea within, were fractionated on a linear iso-osmolar density
      gradient made of urea and sucrose. This resulted in the clear separation of
      vesicles not containing any open channel, staying on top of the gradient, from
      those containing at least one open channel, sedimenting close to the bottom.
      Calculation using Poisson distribution indicated that only between 2 and 3% of
      the OmpA molecules contained open channel. The open form is estimated to allow
      the diffusion of L-arabinose at a rate comparable with that through the OmpF
      porin channel. The open and closed states were relatively stable properties of
      the protein. Denaturation of open form OmpA and its subsequent renaturation
      converted it into a nonfunctional or closed form, suggesting that the open and
      closed forms represent two alternative conformers of this protein.

PMID- 7517936
TI  - Cellular catabolism of normal very low density lipoproteins via the low density
      lipoprotein receptor-related protein/alpha 2-macroglobulin receptor is induced by
      the C-terminal domain of lipoprotein lipase.
AB  - Lipoprotein lipase (LPL) binds to the low density lipoprotein receptor-related
      protein (LRP)/alpha 2-macroglobulin receptor and induces catabolism of normal
      human very low density lipoproteins (VLDL) via LRP in vitro. Recent studies
      showed that the C-terminal domain of LPL can bind LRP in solid phase assays and
      inhibit cellular catabolism of two LRP ligands, activated alpha 2-macroglobulin
      and the 39-kDa receptor-associated protein (Williams, S.E., Inoue, I., Tran, H.,
      Fry, G. L., Pladet, M.W., Iverius, P.-H., Lalouel, J.-M., Chappell, D.A., and
      Strickland, D.K. (1994) J. Biol. Chem. 269, 8653-8658). The current study
      investigated the potential for this region of LPL to promote cellular catabolism
      of VLDL via LRP. A fragment comprising the C-terminal domain of LPL (designated
      LPLC) was expressed in bacteria and found to promote cellular binding, uptake,
      and degradation of normal human VLDL in a dose-dependent manner. These effects
      were present whether LPLC was added simultaneously with 125I-VLDL or was prebound
      to cell surfaces prior to the assay. Mutations involving Lys407, Trp393, Trp394,
      or deletion of the C-terminal 14 residues reduced the effects of LPLC. Three LRP
      binding proteins, the receptor-associated protein, lactoferrin, and a polyclonal
      antibody against LRP, competed for 125I-VLDL degradation induced by LPLC. Heparin
      or heparinase treatment of cells prevented LPLC-induced 125I-VLDL catabolism.
      Thus, cell-surface proteoglycans play an important role in this pathway.
      Interestingly, either LPLC or LPL when added in excess could block LPL-induced
      125I-VLDL degradation presumably by interacting directly with LRP. However,
      unlabeled VLDL could not prevent catabolism of 125I-labeled LPLC or LPL. These
      data show that cellular fates for VLDL versus LPLC or LPL are divergent. This is
      probably due to independent catabolism of the latter via cell-surface
      proteoglycans. In summary, these in vitro studies indicate that a fragment of LPL
      corresponding to the C-terminal domain mimics the native enzyme with respect to
      induction of VLDL catabolism via LRP. Because LPLC lacks the catalytic site of
      native LPL, these studies establish that lipase activity is not required for LRP
      mediated lipoprotein catabolism.

PMID- 7517937
TI  - The mechanism of translational coupling in Escherichia coli. Higher order
      structure in the atpHA mRNA acts as a conformational switch regulating the access
      of de novo initiating ribosomes.
AB  - Bacterial genes are commonly transcribed to form polycistronic mRNAs bearing
      reading frames whose respective translational efficiencies are not independently
      determined. As in many bacterial operons, expression of the atp genes of
      Escherichia coli is strongly influenced by translational coupling. The gene pair
      atpHA is tightly coupled, whereby atpA is translated at least three times more
      efficiently than atpH. However, there is no fixed stoichiometry of coupling:
      mutations in atpH lead to increases in the translation ratio (atpA/atpH) of up to
      approximately 40-fold. We have demonstrated that secondary structure sequestering
      the atpA translational initiation region (TIR) is important to the coupling
      mechanism in that it inhibits de novo translational initiation at the atpA start
      codon. Genetic and structural analyses indicate that this inhibitory structure
      can be induced to refold into a less inhibitory conformation either by
      introducing two single-base substitutions or as a result of ribosomes translating
      atpH. We propose a model in which the secondary structure of the atpA TIR acts
      analogously to a "gating device" in that it restricts de novo ribosomal
      initiation until it is "switched" into a more open conformation. This contrasts
      with the function of a stem-loop structure located immediately downstream of atpA
      and upstream of the Shine-Dalgarno region of atpG, which was found to inhibit
      translation, but not to mediate tight coupling. Results obtained using the
      "specialized" ribosome system of Hui and de Boer ((1987) Proc. Natl. Acad. Sci.
      U.S.A. 84, 4762-4766) indicate that primarily ribosomes reinitiating after
      termination on atpH are responsible for inducing refolding of the atpA TIR. The
      principle of alternative mRNA conformations with different functional properties
      embodied in the model presented here can only be fulfilled by certain types of
      structure. It is likely to operate in several steps of prokaryotic gene
      expression, underlying a range of regulatory events including transcriptional
      attenuation and translational activation.

PMID- 7517938
TI  - Afamin is a new member of the albumin, alpha-fetoprotein, and vitamin D-binding
      protein gene family.
AB  - A novel human serum protein with a molecular mass of 87,000 daltons was purified
      to homogeneity and subjected to amino acid sequence analyses. These sequences
      were used to design oligonucleotide primers and to isolate a full-length cDNA.
      The amino acid sequence encoded by the cDNA shares strong similarity to albumin
      family members and shares the characteristic pattern of Cys residues observed in
      this family. In addition, the gene maps to chromosome 4 as do other members of
      the albumin gene family. Based upon these observations, we conclude that the
      87,000-dalton protein, which we designate afamin (AFM), is the fourth member of
      the albumin family of proteins. Afamin cDNA was stably transfected into Chinese
      hamster ovary cells and recombinant protein (rAFM) was purified from conditioned
      medium. Both rAFM and AFM purified from human serum react with a polyclonal
      antibody that was raised against a synthetic peptide derived from the deduced
      amino acid sequence of AFM.

PMID- 7517939
TI  - Nucleotide-specific transcriptional pausing in the pyrBI leader region of
      Escherichia coli K-12.
AB  - Expression of the pyrBI operon, which encodes the subunits of the pyrimidine
      biosynthetic enzyme aspartate transcarbamylase, is regulated primarily through a
      UTP-sensitive transcriptional attenuation control mechanism in Escherichia coli.
      In this mechanism, the extent of coupling between transcription and translation
      within the pyrBI leader region determines the level of p-independent
      transcriptional termination at an attenuator preceding the pyrB gene. A key
      feature in this mechanism is transcriptional pausing that occurs before the
      attenuator in the pyrBI leader region when UTP concentrations are low. In this
      study, we characterized in detail this UTP-sensitive transcriptional pausing in
      vitro. Our results show that pausing occurs, to different extents, before the
      addition of every uridine residue in the leader transcript. This pausing occurred
      only at low UTP concentrations (20-200 microM) that cause high levels of pyrBI
      expression in vivo. Transcriptional pausing did not occur in the pyrBI leader
      region at 20 microM CTP or ATP and only occurred strongly at one site at 20
      microM GTP. We also demonstrated that NusA functions as a general enhancer of UTP
      sensitive transcriptional pausing in the pyrBI leader region. Finally, we
      identified at the 3' end of the pyrBI attenuator a 3-base region at which
      termination occurs. Selection of termination sites within this region was shifted
      by varying the UTP concentration or including NusA in the transcription reaction
      mixture.

PMID- 7517940
TI  - The FLI-1 and chimeric EWS-FLI-1 oncoproteins display similar DNA binding
      specificities.
AB  - Although recent data have demonstrated that the chimeric EWS-FLI-1 cDNA isolated
      from cases of Ewing's sarcoma can transform NIH 3T3 cells, little is known about
      the basis for this transformation. Since FLI-1 and EWS-FLI-1 contain an Ets
      domain, both proteins may act as sequence-specific transcription factors. Here
      the DNA binding properties of FLI-1 and EWS-FLI-1 have been examined. An epitope
      tagging strategy was developed to determine the optimum DNA-binding sequence of
      FLI-1. The alignment of cloned binding sequences showed a consensus DNA-binding
      site of ACCGGAAG/aT/c. This consensus sequence shows greater specificity for
      sequence 5' of the GGAA core site than those of other Ets proteins. Using several
      truncated forms of FLI-1, we show that the Ets domain is necessary and sufficient
      for the DNA binding specificity of FLI-1. The EWS-FLI-1 protein displayed the
      same DNA binding specificity and affinity as FLI-1 did. Despite their DNA binding
      similarities, the EWS-FLI-1 translocation product is likely to have a distinct
      pattern of expression from that of FLI-1 since the translocation results in the
      replacement of the 5' regulatory region of Fli-1 with that of EWS. Consistent
      with this we found that Fli-1 mRNA expression in lymphocytes was high in
      quiescent cells and disappeared upon activation while EWS mRNA expression was low
      in resting cells and increased in activated T cells. In summary, our data suggest
      that EWS-FLI-1 might act through the same target genes normally regulated by FLI
      1, and EWS-FLI-1-induced transformation may result from dysregulation of FLI-1
      target genes during cell proliferation and differentiation.

PMID- 7517941
TI  - Diffusive and convective solute transport through hemodialysis membranes: a
      hydrodynamic analysis.
AB  - Recent clinical studies have shown that the overall effectiveness of hemodialysis
      is determined by both the convective and diffusive transport of a wide range of
      different molecular weight solutes. In this study, transport data were obtained
      for vitamin B12 and for polydisperse dextrans with a wide range of molecular
      weights using flat sheet Cuprophan and AN69 polyacrylonitrile membranes. The flux
      dependence of the actual sieving coefficient was described using classical
      membrane transport theory, allowing accurate measurements of both the diffusive
      and convective contributions to the overall solute transport through the porous
      structure of these dialysis membranes. Asymptotic membrane sieving coefficients
      and hindered diffusivities were in good agreement with a hydrodynamic model that
      accounts for the membrane pore size distribution through an expression for the
      solute partition coefficient in a random porous medium. This model provides an
      accurate quantitative description of both solute diffusion and convection through
      hemodialysis membranes, which is critical for the effective design and operation
      of hemodialyzers.

PMID- 7517942
TI  - Characterization of caveolin-rich membrane domains isolated from an endothelial
      rich source: implications for human disease.
AB  - Caveolae are 50-100-nm membrane microdomains that represent a subcompartment of
      the plasma membrane. Previous morphological studies have implicated caveolae in
      (a) the transcytosis of macromolecules (including LDL and modified LDLs) across
      capillary endothelial cells, (b) the uptake of small molecules via a process
      termed potocytosis involving GPI-linked receptor molecules and an unknown anion
      transport protein, (c) interactions with the actin-based cytoskeleton, and (d)
      the compartmentalization of certain signaling molecules, including G-protein
      coupled receptors. Caveolin, a 22-kD integral membrane protein, is an important
      structural component of caveolae that was first identified as a major v-Src
      substrate in Rous sarcoma virus transformed cells. This finding initially
      suggested a relationship between caveolin, transmembrane signaling, and cellular
      transformation. We have recently developed a procedure for isolating caveolin
      rich membrane domains from cultured cells. To facilitate biochemical
      manipulations, we have applied this procedure to lung tissue--an endothelial and
      caveolin-rich source-allowing large scale preparation of these complexes. These
      membrane domains retain approximately 85% of caveolin and approximately 55% of a
      GPI-linked marker protein, while they exclude > or = 98% of integral plasma
      membrane protein markers and > or = 99.6% of other organelle-specific membrane
      markers tested. Characterization of these complexes by micro-sequencing and
      immuno-blotting reveals known receptors for modified forms of LDL (scavenger
      receptors: CD 36 and RAGE), multiple GPI-linked proteins, an anion transporter
      (plasma membrane porin), cytoskeletal elements, and cytoplasmic signaling
      molecules--including Src-like kinases, hetero-trimeric G-proteins, and three
      members of the Rap family of small GTPases (Rap 1--the Ras tumor suppressor
      protein, Rap 2, and TC21). At least a fraction of the actin in these complexes
      appeared monomeric (G-actin), suggesting that these domains could represent
      membrane bound sites for microfilament nucleation/assembly during signaling.
      Given that the majority of these proteins are known molecules, our current
      studies provide a systematic basis for evaluating these interactions in vivo.

PMID- 7517943
TI  - Induction of cell migration by pro-urokinase binding to its receptor: possible
      mechanism for signal transduction in human epithelial cells.
AB  - A human epithelial cell line, WISH, and a mouse cell line, LB6-uPAR, transfected
      with the human urokinase receptor (uPAR), both expressed high affinity uPAR but
      undetectable levels of urokinase (uPA). In two independent assays, binding of
      exogenous pro-uPA produced an up to threefold enhancement of migration. The
      migration was time and concentration dependent and did not involve extracellular
      proteolysis. This biologic response suggested that uPAR can trigger an
      intracellular signal. Since this receptor is a glycosyl-phosphatidylinositol
      linked protein, we postulated that it must do so by interacting with other
      proteins, among which, by analogy to other systems, would be a kinase. To test
      this hypothesis, we carried out a solid phase capture of uPAR from WISH cell
      lysates using either antibodies against uPAR or pro-uPA adsorbed to plastic
      wells, followed by in vitro phosphorylation of the immobilized proteins. SDS-PAGE
      and autoradiography revealed two phosphorylated protein bands of 47 and 55 kD.
      Both proteins were phosphorylated on serine residues. Partial sequence of the two
      proteins showed a 100% homology to cytokeratin 18 (CK18) and 8 (CK8),
      respectively. A similar pattern of phosphorylation was obtained with lysates from
      A459 cells, a lung carcinoma, but not HL60, LB6-uPAR or HEp3 cell lysates,
      suggesting that the identified multiprotein uPAR-complex may be specific for
      simple epithelia. Moreover, immunocapture with antibody to another glycosyl
      phosphatidylinositol-linked protein, CD55, which is highly expressed in WISH
      cells, was ineffective. The kinase was tentatively identified as protein kinase
      C, because it was inhibited by an analogue of staurosporine more specific for PKC
      and not by a PKA or tyrosine kinase inhibitors. The kinase was tentatively
      identified as PKC epsilon because of its resistance to PMA down-modulation,
      independence of Ca2+ for activity, and reaction with a specific anti-PKC epsilon
      antibody in Western blots. Cell fractionation into cytosolic and particulate
      fractions revealed that all four proteins, the kinase, uPAR, CK18, and CK8, were
      present in the particulate fraction. In vivo, CK8, and to a lesser degree CK18,
      were found to be phosphorylated on serine residues. Occupation of uPAR elicited a
      time-dependent increase in the phosphorylation intensity of CK8, a cell shape
      change and a redistribution of the cytokeratin filaments. These results strongly
      suggest that uPAR serves not only as an anchor for uPA but participates in a
      signal transduction pathway resulting in a pronounced biological response.

PMID- 7517945
TI  - Human fetal uterine cells: culture, characterization, and analysis of growth
      factor receptor gene expression.
AB  - Peptide growth factors are postulated to have a role in uterine maturation during
      organogenesis. The purpose of this investigation was to establish a model to
      study human fetal uterine development. To that end, we describe an in vitro
      culture system and have characterized the cell types present during the period of
      uterine maturation. In addition, we evaluated the pattern of growth factor
      receptor gene expression in these cultured cells. Uteri were dissected from human
      first and second trimester fetuses (n = 20). Characterization studies were
      performed against three intermediate filament proteins, cytokeratin, vimentin,
      and desmin, and against a fibroblast-associated cell surface antigen. Ribonucleic
      acid was extracted from pure stroma-like cultures, and reverse transcription
      polymerase chain reaction (RT-PCR) was used to amplify sequences specific for the
      epidermal growth factor receptor (EGF-R), fibroblast growth factor receptor (FGF
      R), and the insulin receptor (I-R). Two predominant cell types were identified in
      the cultured fetal tissue: stroma-like cells and clusters of uterine epithelium.
      Immunofluorescent studies demonstrated positive expression of cytokeratin,
      vimentin, and a fibroblast-associated antigen in the fetal stroma-like cells, in
      contrast to adult stromal cells, which consistently expressed only vimentin.
      Using RT-PCR, the uterine cells were positive for the EGF-R, two forms of the FGF
      R, and two forms of the I-R. In conclusion, we provide the first report of a
      human fetal cell culture system. Characterization studies of fetal stroma-like
      cells demonstrate immunoreactivity to vimentin, cytokeratin, and a fibroblast
      antigen, in contrast to the adult stromal cell, which consistently expressed only
      vimentin. Using RT-PCR, we found that messenger ribonucleic acids for the EGF-R
      and two forms of both the FGF-R and I-R are expressed. This model may be useful
      for studying the dynamics of human uterine development in vitro.

PMID- 7517944
TI  - Activation of the alpha 4 beta 1 integrin through the beta 1 subunit induces
      recognition of the RGDS sequence in fibronectin.
AB  - Lymphocyte attachment to fibronectin is mainly mediated by the interaction of
      alpha 5 beta 1 and alpha 4 beta 1 integrins with the RGD and CS-1/Hep II sites,
      respectively. We have recently shown that the anti-beta 1 mAb TS2/16 can convert
      the partly active alpha 4 beta 1 present on certain hemopoietic cells that
      recognizes CS-1 but not Hep II, to a high avidity form that binds both ligands.
      In this report we have studied whether mAb TS2/16 also affects alpha 4 beta 1
      ligand specificity. Incubation of the B cell lines Ramos and Daudi (which lack
      alpha 5 beta 1) with mAb TS2/16 induced specific attachment to an 80-kD fragment
      which lacks CS-1 and Hep II and contains the RGD sequence. mAbs anti-alpha 4 and
      the synthetic peptides CS-1 and IDAPS inhibited adhesion to the 80-kD fragment
      thus implying alpha 4 beta 1 as the receptor for this fragment. Interestingly,
      the synthetic peptide GRGDSPC and a 15-kD peptic fibronectin fragment containing
      the RGD sequence also inhibited B cell adhesion to the 80-kD fragment. Because we
      have previously shown that RGD peptides do not affect the constitutive function
      of alpha 4 beta 1, we tested whether TS2/16-activated alpha 4 beta 1 acquired the
      capacity to recognize RGD. Indeed RGD peptides inhibited TS2/16-treated B cell
      adhesion to a 38-kD fragment containing CS-1 and Hep II but did not affect
      binding of untreated cells to this fragment. An anti-fibronectin mAb reactive
      with an epitope on or near the RGD sequence also efficiently inhibited cell
      adhesion to the 80-kD fragment, indicating that the RGD sequence is a novel
      adhesive ligand for activated alpha 4 beta 1. These results emphasize the role of
      alpha 4 beta 1 as a receptor with different ligand specificities according to the
      activation state, a fact that may be important for lymphocyte migration,
      localization, and function.

PMID- 7517946
TI  - Polyclonal and monoclonal thyroid nodules coexist within human multinodular
      goiters.
AB  - Although somatic mutations have been identified in a subset of thyroid nodules,
      the pathogenesis of nodules in multinodular goiters remains unclear. Clonal
      analysis indicates whether a nodule arises from the polyclonal proliferation of a
      group of cells or forms a clone from a genetically altered cell. Individual
      thyroid nodules have been shown to be of polyclonal or monoclonal origin. In this
      study we examined the clonality of several different nodules in patients with
      multinodular goiters. Clonality was established using the X-chromosomal probe M27
      beta, which detects a multiallelic polymorphism at the locus DXS255 in 90% of
      females. Twenty-five nodules from 9 multinodular goiters were analyzed; 9 nodules
      were polyclonal, and 16 were monoclonal. Three goiters contained only polyclonal
      nodules, whereas 3 contained only monoclonal nodules. Polyclonal and monoclonal
      nodules coexisted in 3 goiters. In 2 goiters, the monoclonal nodules were shown
      to derive from different progenitor cells. We conclude that polyclonal and
      monoclonal nodules may coexist in multinodular goiters and that monoclonal
      nodules can originate from different cells. The coexistence of polyclonal and
      monoclonal nodules suggests that different pathogenic mechanisms occur
      simultaneously or that monoclonal nodules emerge secondarily from a polyclonal
      population due to a growth advantage from a genetically altered cell.

PMID- 7517948
TI  - Messenger RNA encoding the insulin-like growth factors and their binding
      proteins, in women with fibroids, pretreated with luteinizing hormone-releasing
      hormone agonists.
AB  - The primary objective of this study was to suggest a possible mechanism of action
      of luteinizing hormone-releasing hormone agonist (LHRHa) on fibroids. This was
      performed by investigating insulin-like growth factor (IGF)-I, IGF-II and IGF
      binding protein (IGFBP)-1, -2 and -3 mRNA expression in uterine fibroids from
      women rendered hypo-oestrogenic by LHRHa, using Northern blot analysis. Nine
      women with fibroids, who were rendered hypo-oestrogenic from at least 4 months
      pretreatment with LHRHa therapy prior to undergoing myomectomy were investigated.
      Our results showed that IGF-I, IGF-II, IGFBP-2 and -3 mRNAs were expressed in
      uterine fibroids, and that IGFBP-1 mRNA or protein was not detected in fibroids.
      Western ligand blotting showed the presence of IGFBP-2 and -3 proteins, and when
      compared with a group of women with fibroids not treated with LHRHa (B.J.
      Vollenhoven et al., 1993, J. Clin. Endocrinol. Metab., 76, 1106-1110) we found
      that there was no difference in the relative abundance for each of the factors
      between the two groups of women. Therefore, LHRHa act to decrease fibroid size
      via induction of a hypo-oestrogenic state rather than by changes in the IGFs and
      their IGFBPs.

PMID- 7517947
TI  - Follistatin antagonizes the effects of activin-A on steroidogenesis in human
      luteinizing granulosa cells.
AB  - Activin-A decreases progesterone secretion and aromatase activity in cultured
      human luteinizing granulosa cells. Follistatin is a binding protein for activin
      and inhibin produced by granulosa cells and present in follicular fluid. The
      present study examines the hypothesis that follistatin reverses the actions of
      activin-A on human granulosa cells. Granulosa cells from women undergoing ovarian
      stimulation for in vitro fertilization were cultured in defined medium with
      recombinant human (rh) activin-A and purified porcine follistatin. Follistatin
      completely reversed the inhibition of basal progesterone production by rh-activin
      A, but only when added in a greater than 2:1 molar ratio to activin-A. Although
      variable effects of activin-A on aromatase activity were observed in these
      studies, follistatin also antagonized these effects. Follistatin had no effect in
      the absence of added activin-A. rh-Inhibin-A did not alter steroidogenesis by
      granulosa cells either with or without added activin-A. Even when added in a 45
      fold molar excess, inhibin-A did not displace sufficient activin-A from
      follistatin to inhibit progesterone secretion. This suggests that the affinity of
      inhibin-A for follistatin is much lower than that of activin-A, and/or that
      activin-A bound to follistatin dissociates slowly. alpha 2-Macroglobulin, another
      activin-binding protein, did not alter the inhibition of progesterone production
      by activin-A. We conclude that in human granulosa cells, follistatin, but not
      alpha 2-macroglobulin or inhibin-A, acts to modulate the actions of activin-A.
      Follistatin and activin may be viewed as components of an autocrine/paracrine
      system within the human follicle that regulate the differentiated functions of
      granulosa cells.

PMID- 7517949
TI  - Decidualization of human endometrial stromal cells in vitro: effects of progestin
      and relaxin on the ultrastructure and production of decidual secretory proteins.
AB  - Decidual cells arise by proliferation and differentiation of endometrial stromal
      cells of the uterus after appropriate stimulation by ovarian hormones. Previously
      we have shown that progestin and relaxin stimulate the secretion of several
      decidual-cell-specific secretory proteins in a long-term primary cell culture
      system. We now report the effects of progestin and relaxin on the morphology of
      stromal cells in association with the production rate of two major decidual
      secretory proteins, prolactin and insulin-like growth factor binding protein-1
      (IGFBP-1). Stromal cells were cultured in RPMI 1640 and 2% fetal bovine serum for
      22 days under control conditions (no hormone), with relaxin or
      medroxyprogesterone acetate (MPA), or MPA plus relaxin. Cells treated with MPA
      alone or MPA plus porcine relaxin grew to a high density with many areas of
      heaping while control cells and cells grown in medium containing relaxin alone
      formed discontinuous layers. The cytoplasm was distinguished by aggregates of
      rough endoplasmic reticulum and secretory granules. Surfaces of cells treated
      with MPA plus relaxin had clusters of short blunt processes containing secretory
      granules. The processes were rarely seen in cells exposed to MPA alone and
      completely absent in control cells or cells exposed to relaxin alone.
      Intercellular space was greatly widened in cells treated with MPA alone or MPA
      plus relaxin. There were many extended gap junctions in MPA- and relaxin-treated
      cells in contrast to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517950
TI  - Molecular analysis of rRNA and cholera toxin genes carried by the new epidemic
      strain of toxigenic Vibrio cholerae O139 synonym Bengal.
AB  - Vibrio cholerae O139 synonym Bengal recently caused large epidemics of cholera
      like disease in Bangladesh and India. We compared the restriction fragment length
      polymorphisms of ctxA and rRNA genes (ribotypes) in 27 isolates of V. cholerae
      O139 from patients in Bangladesh and India with those of 48 isolates of V.
      cholerae O1 from patients and 21 V. cholerae isolates from surface waters in
      Bangladesh, which included 2 O139 and 19 other non-O1 isolates. Ribotyping of the
      isolates with BglI revealed that all 29 isolates of O139 vibrios belonged to a
      single ribotype, suggesting a clonal nature of the infection. However, the O139
      vibrios comprised two ctxA genotypes and carried three or more copies of the ctxA
      gene, and the chromosomal locations of these copies were unlike those of the El
      Tor or classical vibrios. Analysis of the restriction fragment length
      polymorphisms of the rRNA genes suggested that V. cholerae O139 isolates are more
      closely related to El Tor strains of V. cholerae O1 than were 19 other non-O1
      vibrios and 33 classical V. cholerae O1 isolates that were studied. However,
      further studies are needed to determine whether V. cholerae O139 originated from
      mutations and genetic changes in a V. cholerae O1 strain or was due to the
      acquisition of virulence genes by a previously unknown V. cholerae non-O1 strain.

PMID- 7517951
TI  - Modified technique for efficient detection of microsporidia.
AB  - Changes in temperature (from room temperature to 50 degrees C) and staining time
      (from 90 to 10 min) were evaluated as a means of improving the detection of
      microsporidia from stool specimens. A blinded and independent comparison of 50
      known positive matched-specimen pairs by three technologists resulted in
      consistently easier microscopic detection. The background is clearer, and spores
      stain more intensely. Staining time is reduced by 80 min.

PMID- 7517952
TI  - Importance of the fiberoptic endoscope cleaning procedure for detection of
      Helicobacter pylori in gastric biopsy specimens by PCR.
AB  - A 16S ribosomal DNA-based PCR appeared to be a sensitive test for the detection
      of infection by Helicobacter pylori in 31 patients when compared with culturing
      and histological and serological techniques. For five patients, PCR was the only
      test with a positive result. H. pylori DNA was also found in gastrointestinal
      equipment even after standard intensive combined manual and machine cleaning. We
      therefore conclude that a reliable validation of PCR for the detection of H.
      pylori in gastric biopsy specimens is possible only when the cleaning and
      disinfection method used has been proven to remove all H. pylori DNA from
      gastrointestinal equipment. An adequate cleaning and disinfection method for the
      removal of H. pylori DNA from fiberoptic endoscopes is described.

PMID- 7517953
TI  - Linkage analysis of geographic and clinical clusters in Pseudomonas cepacia
      infections by multilocus enzyme electrophoresis and ribotyping.
AB  - Multilocus enzyme electrophoresis and ribotyping were used to characterize 83
      strains of Pseudomonas cepacia, mostly isolated from cystic fibrosis (CF)
      patients, although a number of isolates from non-CF nosocomial infections and
      reference environmental strains were represented. Twenty enzyme electrophoretic
      types (ETs) were determined; of these, one clone (ET12) was associated with six
      of nine ribotypes (RTs) said to be geographically representative of the United
      Kingdom and all of the Ontario (Canada) isolates from CF patients. This clone was
      not associated with nosocomial infections or environmental strains and was never
      found in CF isolates from British Columbia or Nova Scotia, Canada, or a center in
      the eastern United States. Individual isolate EcoRI RT signatures did not cluster
      geographically as did the ET signatures by clonal analysis. Frequently RTs
      occurred in more than a single ET. Known point source focal nosocomial outbreaks
      were typified by single ETs and stable RTs. Dendrographic analysis of the strains
      grouped those strains from CF patients, nosocomial outbreaks, and environmental
      sources into separate ET families, and diversity analysis indicated that, with
      the exception of ET17, CF isolates clustered in unique and closely related ETs
      different from those from nosocomial and environmental sources. This study has
      also shown the potential of multilocus enzyme electrophoresis to monitor the
      intercontinental spread of P. cepacia strains in CF patients, and this may have a
      significant impact on plans for CF patient summer camps and design of infection
      control practices. Whether the intercontinental ET12 clone, which predominates in
      the United Kingdom and the province of Ontario, linked by summer camp
      acquisition, has increased virulence for CF patients remains to be established.

PMID- 7517954
TI  - Guidelines for investigation of the alpha and beta thalassaemia traits. The
      Thalassaemia Working Party of the BCSH General Haematology Task Force.

PMID- 7517955
TI  - Cytokeratin immunostaining for detection of biliary epithelium: its use in
      counting bile ducts in cases of liver allograft rejection.
AB  - AIMS: To see how useful the application of a bile duct specific cytokeratin
      antibody (AE1) was in identifying and counting bile ducts in liver allograft
      biopsy specimens. METHODS: Eighteen liver biopsy specimens showing acute
      rejection and 17 biopsy specimens plus six hepatectomy specimens showing chronic
      rejection were studied. Serial sections were cut and stained with haematoxylin
      and eosin and AE1 antibody. Two pathologists (RFH and KP) examined the sections
      with respect to a range of histological features. RESULTS: Similar numbers of
      bile ducts were identified on haematoxylin and eosin sections as on corresponding
      sections stained by AE1 in cases of acute rejection and end stage chronic
      rejection. Greater numbers of bile ducts were identified by AE1 during the early
      stages of chronic rejection, especially when dense portal inflammatory
      infiltrates were present. These were often incomplete structures or individual
      cells within portal tracts, and bile ducts subsequently disappeared in all cases.
      Ductular proliferation was clearly shown by AE1 in acute rejection and the extent
      seemed to correlate with the severity of rejection present. By contrast, no
      ductular proliferation was observed in chronic rejection. CONCLUSIONS:
      Haematoxylin and eosin stained sections are adequate for counting bile ducts in
      most biopsy specimens from patients with suspected chronic rejection.
      Immunostaining for biliary cytokeratins using AE1 is of limited use in occasional
      cases where bile ducts are obscured by inflammatory cells.

PMID- 7517956
TI  - An unusual epithelial pleomorphic giant cell tumour of the pancreas with
      osteoclast-type cells.
AB  - A case of giant cell tumour of the pancreas with a mixture of pleomorphic giant
      cells and osteoclast-like cells is described. This association is rare and its
      histogenesis has been debated. The presence of a small differentiated
      adenocarcinomatous area at the periphery of the tumour indicates an epithelial
      origin. Moreover, some pleomorphic cells were positive for keratin (KL1). The
      osteoclast-like cells strongly expressed CD68 (a marker of histiomonocytic
      lineage) and did not show proliferative activity. They probably correspond to an
      unusual reaction of the stroma. Their clinical importance in this type of tumour
      remains unknown.

PMID- 7517957
TI  - Recent advances in the study of tumour invasion and metastasis.

PMID- 7517958
TI  - Evaluation of a safe sputum processing method for detecting tuberculosis.
AB  - AIMS: To evaluate a safe sputum processing method for detection of tuberculosis
      in developing countries. METHODS: A sample processing method was developed in
      which acid fast bacilli were killed with 1% sodium hypochlorite and concentrated
      by flotation on a layer of xylene before staining by the Ziehl Neelsen or
      auramine O methods. RESULTS: Best results were obtained by auramine O staining
      after flotation. Staining by the Ziehl Neelsen method after flotation gave better
      results than direct Ziehl Neelsen staining without flotation. CONCLUSIONS: The
      flotation method with Ziehl Neelsen staining offers advantages for smear
      preparation in the tuberculosis control programmes of developing countries.

PMID- 7517959
TI  - VS38: a new monoclonal antibody for detecting plasma cell differentiation in
      routine sections.
AB  - AIMS: To characterise a new mouse monoclonal antibody, VS38, which recognises an
      intracytoplasmic antigen of 64 kilodaltons present in normal and neoplastic
      plasma cells; and to establish its value as a diagnostic reagent for routine
      pathological practice. METHODS: A range of normal and neoplastic tissue sections,
      both frozen and routinely fixed, were immunostained, using the microwave method
      of antigen retrieval for routinely fixed specimens. The antibody was also tested
      on blood and bone marrow specimens and a range of human cell lines. The molecular
      weight of the antigen recognised by the antibody was obtained by western blot
      analysis. FACS analysis was used to demonstrate the cellular location of the
      antigen and its presence on tonsil cell suspensions and myeloma cases. RESULTS:
      VS38 recognised normal and neoplastic plasma cells in all of the tissues,
      including all routinely fixed plasma cell neoplasms tested. The antibody also
      weakly stained epithelial elements within the tissue but was absent from
      haemopoietic cells of other lineages. CONCLUSION: Antibody VS38 is of potential
      value in identifying myeloma or plasmacytoma in bone marrow or other tissues. It
      differentiates lymphoplasmacytoid lymphoma from lymphocytic and follicular
      lymphoma. It also subdivides large cell lymphomas into two groups which may be a
      more reliable method of separating these tumours than morphology alone.

PMID- 7517960
TI  - Microwave antigen retrieval in immunocytochemistry: a study of 80 antibodies.
AB  - AIMS: To evaluate the effect of microwave irradiation on the staining quality of
      a range of commonly used primary antibodies in archival, formalin fixed, paraffin
      wax embedded material, with emphasis on antibodies that have previously worked
      successfully only on frozen tissue. METHODS: Immunocytochemistry (streptavidin
      biotin complex technique) was performed on histological sections of a range of
      normal and pathological tissues, after varying treatment with microwave
      irradiation. The staining quality of each antibody was compared with that
      achieved without prior treatment of the sections or after enzyme predigestion.
      RESULTS: Microwave irradiation permitted successful immunostaining with 20
      antibodies that stained only frozen tissues before. The staining characteristics
      of 21 antibodies that were already known to stain formalin fixed, paraffin wax
      embedded material were improved. Another 39 antibodies did not show enhanced
      staining with microwave irradiation. The method preserves tissue morphology and
      produces more consistent staining than that achieved by enzyme predigestion with
      many antibodies. Microwave irradiation may also allow some primary antibodies to
      be used at higher working dilutions. The citrate buffer used in this study avoids
      the necessity of exposure to heavy metal salts. CONCLUSIONS: Microwave antigen
      retrieval represents an important technical advance within immunocytochemistry
      that will greatly increase the range of antibodies which can be used to study
      formalin fixed, paraffin wax embedded tissues.

PMID- 7517961
TI  - The return of phosphorylated and nonphosphorylated epitopes of neurofilament
      proteins to the regenerating optic nerve of Xenopus laevis.
AB  - Neurofilament proteins of mammalian axotomized peripheral axons, which regenerate
      effectively, resemble those of embryonic axons. However, injured centrally
      projecting mammalian axons, which fail to regenerate, have very different
      neurofilament compositions than during development. If changes in neurofilament
      composition after injury reflect the ability of axotomized neurons to regenerate
      effectively, then the neurofilaments of centrally projecting axons that can
      regenerate should more closely resemble those of developing axons. In this study,
      the neurofilament compositions of injured optic axons of the frog, Xenopus
      laevis, were examined, since these axons can regenerate a fully functional
      projection. Antibodies to phosphorylated and nonphosphorylated forms of
      neurofilament proteins that had been used previously to study the neurofilament
      composition of newly developing X. laevis optic axons were used in
      immunocytochemical studies to examine the return of neurofilaments to the optic
      nerve after an intraorbital nerve crush. Intraocularly injected wheat germ
      agglutinin conjugated to horseradish peroxidase was used to label the
      regenerating axons independently of their neurofilaments. Neurofilament
      immunoreactivities disappeared rapidly from crushed axons during the first week
      after surgery. By nine days after surgery, antibodies to nonphosphorylated forms
      of middle (NF-M) and low molecular weight (NF-L) neurofilament proteins and the
      Xenopus neuronal intermediate filament protein (XNIF) began to stain the nerve
      just beyond the lesion. By this time, however, growing axonal terminals had
      reached the optic chiasm. Antibodies to phosphorylated epitopes of NF-M began to
      stain axons at 15 days, just as growing axons began to arrive at the optic
      tectum. Nonphosphorylated high molecular weight neurofilament protein (NF-H)
      began to appear in axons between 18 and 21 days after surgery. Thus, the
      reappearance of neurofilaments during optic axon regeneration resembled the
      general pattern seen during development. The chief difference between development
      and regeneration was that neurofilament epitopes took longer to emerge during
      regeneration. One possibility is that cues encountered along the optic pathway
      influence the neurofilament composition of retinal ganglion cell axons. Then, the
      greater distances travelled by regenerating axons could account for the longer
      time taken for their neurofilament compositions to mature.

PMID- 7517962
TI  - Distribution of substance P-like immunoreactive neurons and terminals throughout
      the nucleus of the solitary tract in the human brainstem.
AB  - The anatomical distribution of substance P-like immunoreactivity across the
      subnuclear divisions of the nucleus of the solitary tract has been examined in
      the human medulla oblongata. A differential distribution of neurons, fibres, and
      terminals was observed throughout the ten subnuclear divisions of this nucleus.
      Substance P-like immunoreactive neurons were observed most frequently in the
      nucleus gelatinosus, with moderate numbers in the medial, intermediate subnuclei
      and very few in the commissural, ventral, dorsal, and dorsolateral subnuclei. The
      paracommissural, ventrolateral, and interstitial subnuclei did not contain
      substance P-like-immunoreactive neurons. These neurons were typically bipolar and
      moderate-sized to large, except for the neurons in the nucleus gelatinosus, which
      were substantially smaller. The highest densities of fibres and terminals were
      observed in the gelatinosus, medial, and intermediate nuclei, with moderate
      densities in the paracommissural and dorsal subnuclei. Sparse substance P-like
      immunoreactive fibres and terminals were seen in the ventral and interstitial
      nuclei as well as within the solitary tract. The dorsolateral nucleus was
      characterized by a light distribution of fibres and terminals, except for a dense
      aggregation along its lateralmost border. A prominent innervation of pigmented
      neurons by substance P-like-immunoreactive terminals and fibres was also observed
      in the dorsolateral nucleus. The results reveal that the subnuclear complexity of
      the nucleus of the solitary tract is richly reflected by its differential pattern
      of substance P-like-immunoreactive structures.

PMID- 7517963
TI  - Differential expression of keratins in goldfish optic nerve during regeneration.
AB  - The goldfish visual pathway, unlike the visual pathway of higher vertebrates,
      retains continuous growth and development throughout life and is capable of
      functional regeneration. The structure and expression of proteins that support
      the physiological attributes of this system are of interest. Glial cells in this
      pathway express keratins as the predominant intermediate filament proteins rather
      than the expected glial fibrillary acidic protein. Previously we identified and
      characterized cDNA clones representing two type I keratins from the goldfish
      optic nerve, GK48 and GK49. The GK48 protein is the type I keratin partner to the
      type II keratin ON3, while the GK49 protein is expressed in a different cell
      type. Here, we extend our studies on the expression of mRNA for the GK48, GK49,
      and ON3 proteins at the early stages of optic nerve regeneration. RNase
      protection assays show that at 10 days post-crush, there is no overall change in
      levels of mRNA for these proteins as compared to uncrushed control nerves and
      nerves from unoperated fish. In addition, we show by in situ hybridization that
      the GK49 protein shows no changes in its distribution of mRNA in the optic nerve
      after crush. In contrast, the levels of GK48 and ON3 mRNA are greatly reduced
      within the crush zone. However, these two mRNAs are differentially expressed at
      different time points during regeneration, with GK48 mRNA appearing in the crush
      zone before ON3. These results indicate that the mRNA for the GK48 and ON3
      proteins are differentially regulated during regeneration and that these two
      proteins are expressed in a different cell type from the GK49 protein.

PMID- 7517964
TI  - Topographic spinocerebellar mossy fiber projections are maintained in the lurcher
      mutant.
AB  - A variety of recent studies of cerebellar development have focused attention on
      the role of Purkinje cells as organizing elements for the topography of afferent
      fiber connectivity in the cerebellum. We have investigated the involvement of
      Purkinje and granule cells in the maintenance of topographic spinocerebellar
      mossy fiber projections by analyzing the distribution of spinocerebellar mossy
      fiber terminals in lurcher (+/Lc) mutant mice. Purkinje cells in the +/Lc mutant
      degenerate starting after the first week of postnatal development because of an
      intrinsic genetic defect. The loss of their Purkinje cell targets also results in
      the death of 90% of the granule cells. We examined the distribution of
      spinocerebellar mossy fiber terminals in the juvenile and adult +/Lc mutant to
      determine how the pattern of afferent projections is affected by the loss of
      Purkinje cells shortly after innervation of the cerebellum. Labeling of
      spinocerebellar mossy fiber terminals with WGA-HRP in the P38 and adult +/Lc
      mutant showed that, despite the loss of almost all Purkinje cells and 90% of the
      granule cells, spinocerebellar mossy fibers project to the appropriate folia and
      segregate into relatively normal parasagittal bands. While we cannot rule out the
      possibility that Purkinje cells may be involved in the initial establishment of
      topographic maps, our results indicate that Purkinje cells are not necessary for
      the maintenance of the normal spinocerebellar mossy fiber topographic map.

PMID- 7517965
TI  - Distribution and proportions of GABA-immunoreactive neurons in cat primary
      somatosensory cortex.
AB  - Certain receptive field properties of cortical neurons depend upon inhibitory,
      GABAergic inputs. In the somatosensory cortex, iontophoresis of bicuculline, a
      GABAA receptor blocker, results in enlargement of receptive fields. However,
      bicuculline's effectiveness in changing receptive field size varies with the
      neuron's adaptation characteristics, location within a particular submodality
      region, and laminar location. To test whether regional differences in the
      effectiveness of bicuculline are correlated with the distribution of cortical
      GABAergic neurons, we determined the numbers and proportions of GABA
      immunoreactive [GABA(+)] neurons within cat primary somatosensory cortex. The
      laminar distribution of GABA(+) neurons was similar across all four
      cytoarchitectonic areas of primary somatosensory cortex, with layer II containing
      the highest areal density of GABA(+) neurons. Numerical proportions of GABA(+)
      neurons in the total neuron population were similar in areas 3b and 2 (29.8% and
      22.6%, respectively). Laminar distributions of the proportions of GABA(+) neurons
      were also similar in these two areas; in both areas, layer I contained the
      highest proportion of GABA(+) neurons. The laminar distributions of GABA(+)
      neuron densities as well as GABA(+) neuron proportions differed from the reported
      laminar distribution of bicuculline effects on receptive field size. Moreover,
      within area 3b, these measures showed no evident patterns that might correspond
      to rapidly adapting and slowly adapting submodality regions.

PMID- 7517967
TI  - Compartmentation of brain-type creatine kinase and ubiquitous mitochondrial
      creatine kinase in neurons: evidence for a creatine phosphate energy shuttle in
      adult rat brain.
AB  - Multiple isoforms of creatine kinase (CK) are expressed in specific cell types as
      part of an energy delivery or shuttle system. To test the hypothesis that neurons
      utilize a creatine phosphate energy shuttle, we examined the pattern of CK
      isoform expression and localization in adult rat brain. Two isoforms of CK are
      present in brain extracts, "brain-type," or BCK, and the ubiquitous form of the
      mitochondrial CK (uMtCK), as detected by enzyme activity following nondenaturing
      electrophoresis and by Western blotting following denaturing electrophoresis. In
      formalin-fixed and paraffin-embedded sections of rat brain, uMtCK immunostaining
      is detected in the somata of all Golgi type I neurons in the cerebellum, pontine
      reticular formation, red nucleus, hippocampus, and cerebral cortex.
      Immunostaining for uMtCK appears throughout the cell body but not in nuclei. BCK
      immunostaining is also present in somata of Golgi type I neurons in the
      cerebellum, red nucleus, and pons and is distributed throughout the cell body and
      within nuclei. BCK immunostaining also appears in neuronal processes and is
      concentrated in the molecular layers of the cerebellum and the hippocampus and in
      cortical pyramidal cell dendrites. These results demonstrate a coordinate pattern
      of expression and compartmentation of BCK and uMtCK isoforms in neurons, which
      provides an anatomic basis for the transfer of metabolic energy via a creatine
      phosphate energy shuttle.

PMID- 7517968
TI  - Influence of carbon dioxide anesthesia on chlorpyrifos toxicity in the German
      cockroach (Dictyoptera: Blattellidae).
AB  - Insecticide-susceptible (Orlando normal) and multi-insecticide-resistant (Village
      Green) adult male German cockroaches, Blattella germanica (L.), were exposed to
      carbon dioxide (CO2) gas in either varying durations or multiple exposures of
      fixed duration followed by topical treatment with acetone or chlorpyrifos (LD25)
      to evaluate the effect of CO2 anesthesia on chlorpyrifos toxicity. CO2 anesthesia
      did not increase chlorpyrifos toxicity in either strain regardless of exposure
      duration up to 1 h. However, multiple CO2-induced knockdowns alone caused
      mortality and increased chlorpyrifos toxicity. Twenty-four-hour weight loss was
      independent of CO2 duration exposure by strain. Village Green and Orlando
      cockroaches lost 5.3 and 7.6% of their weight in 24 h when treated with acetone
      and 10.5 and 12.8% when treated with chlorpyrifos, respectively. Conversely, 0-
      and 24-h weight loss increased with increasing CO2-induced knockdowns regardless
      of strain or topical treatment. Based on these results, CO2 used either once of
      limited duration (< or = 15 min) or multiple times of short duration, not to
      exceed four total knockdowns, does not increase chlorpyrifos toxicity in the
      adult male German cockroach.

PMID- 7517966
TI  - Localization of immunoreactive ubiquitin in the nervous system of the Manduca
      sexta moth.
AB  - Selective neuronal death is a normal component of metamorphosis in the moth,
      Manduca sexta. In particular, the three unfused abdominal ganglia of the ventral
      nerve cord serve as a useful experimental preparation in which to study the
      regulation of the molecular mechanisms that mediate programmed cell death.
      Ubiquitin, a highly conserved 76-amino acid protein found in all eukaryotic
      cells, has previously been shown to be present in increased amounts in some
      tissues undergoing programmed cell death (e.g., larval intersegmental muscles in
      Manduca sexta moths, dying cells in developing tunicates), but not in others (T
      cells, Drosophila ommatidial cells, cultured sympathetic neurons deprived of
      nerve growth factor). It has been hypothesized that the need for ubiquitin
      dependent proteolysis is increased in dying cells, and that the accumulation of
      ubiquitin might serve as an early marker for cells committed to die.
      Immunohistochemical localization of ubiquitin at the light microscopic level in
      the abdominal ganglia of Manduca sexta suggests that this protein plays a number
      of important roles in neuronal physiology and may be associated with the death of
      some neurons in this tissue. The most intense staining of neuronal cytoplasm,
      however, was found not in dying neurons, but instead in sets of persisting
      neurons that may serve a primarily neurosecretory or neuromodulatory function.
      The staining obtained in these cells with antibodies directed against ubiquitin
      was developmentally regulated.

PMID- 7517969
TI  - Human monoclonal or polyclonal antibodies recognize predominantly discontinuous
      epitopes on bee venom phospholipase A2.
AB  - BACKGROUND: Two hybridomas, which secrete human monoclonal antibodies of IgG4
      isotype specific for the main bee venom antigen/allergen phospholipase A2, were
      generated. The antigenic determinants recognized by these antibodies were mapped
      and compared with the binding sites of murine monoclonal and human polyclonal
      antibodies raised against the same antigen. METHODS: Two hybridomas were
      developed by fusing heteromyelomas to Epstein-Barr virus immortalized B cells
      obtained from beekeepers. The cloned hybridomas were stable and secreted up to 40
      mg/L of antibody into the culture supernatant. Phospholipase A2 specificity of
      the human monoclonal antibodies was confirmed by binding and inhibition ELISA and
      by Western blot analysis. Epitope mapping on phospholipase A2 was done with the
      PEPSCAN method and ELISA techniques. RESULTS: The epitopes recognized by the
      human monoclonal antibodies were shown to be discontinuous and did not contain
      the sugar residue. Similar results were obtained with polyclonal antibodies of
      IgG4 isotype (from beekeepers) specific for phospholipase A2, which could also
      inhibit the binding of the human monoclonal antibodies to phospholipase A2. In
      contrast, antigen binding of the human monoclonal antibodies could not be
      inhibited by murine monoclonal antibodies against bee venom phospholipase A2.
      CONCLUSIONS: The data indicate that the human monoclonal antibodies obtained are
      representative of a part of the polyclonal immune response to phospholipase A2
      from beekeepers and may allow a more precise analysis of the humoral immune
      response to phospholipase A2 that is associated with protection.

PMID- 7517970
TI  - Interference with the binding of a naturally processed peptide to class II alters
      the immunodominance of T cell epitopes in vivo.
AB  - T lymphocytes elicited in response to an immunizing Ag usually recognize only one
      or a few immunodominant peptides. The mechanisms governing this process are
      poorly understood. This study examines the consequences of peptide competition on
      immunodominance. Immunization of B10.A mice with the native Staphylococcus aureus
      nuclease protein primes T cells to the dominant 86-100 peptide presented in
      association with I-Ek class II molecules. To render the 86-100 peptide incapable
      of binding to the class II molecule, single amino acid substitutions were
      introduced in the native Staphylococcus aureus nuclease protein within a putative
      I-Ek class II binding motif. Introduction of residue changes at positions 89 and
      91 in the protein prevents 86-100-specific T cell clone recognition of the
      protein in vitro. Competition studies demonstrate that substitutions at residues
      89 or 91 decreased the I-Ek binding affinity of the 86-100 peptide. Immunization
      of B10.A mice with the L89F or Y91S mutant proteins does not prime T cells to the
      dominant 86-100 peptide; T cells are primed instead to I-Ek-restricted
      subdominant peptide(s) encompassed by the residues 111-135. In vitro binding
      studies demonstrate that both the 111-130 and 116-135 synthetic peptides compete
      with a labeled I-Ek-binding peptide 20-fold less efficiently than the dominant 86
      100 peptide, suggesting that these subdominant peptides may be of lower binding
      affinity than the dominant 86-100 peptide. These results support the hypothesis
      that dominance is dependent on peptide binding affinity for the appropriate class
      II molecule and the ability to compete with other peptides, derived from the same
      Ag, for class II binding.

PMID- 7517971
TI  - The role of CD40-CD40 ligand interaction in human T cell-B cell collaboration.
AB  - Interactions between CD40 on B cells and its ligand on activated T cells have
      been reported to play an important role in T cell-B cell collaboration. In this
      current study, a mAb against the human CD40 ligand (5c8) was used to investigate
      the impact of CD40-CD40 ligand interactions in the initial activation of normal
      human peripheral blood B cells and in subsequent proliferation and
      differentiation. B cells were activated by co-culture with anti-CD3-stimulated
      normal T cells. mAb against CD40 ligand blocked initial T cell-dependent B cell
      activation, as assessed by [3H]uridine incorporation and IL-2R expression.
      Subsequent B cell proliferation and differentiation were also inhibited by this
      mAb. In addition to its effect on B cell activation, 5c8 also inhibited the
      capacity of B cells to augment IL-2 production by anti-CD3 activated T cells,
      implying a role for CD40-CD40 ligand interactions in the accessory function of B
      cells. Despite the importance of CD40-CD40 ligand interactions in T cell-B cell
      collaboration, CD40 ligand-deficient T cell clones were found to induce initial
      activation of B cells and support Ig production. This effect was only marginally
      effected by mAb to LFA-1 and ICAM-1, suggesting that additional interaction
      molecules play a role in T cell-B cell collaboration. Taken together, the data
      indicate that CD40-CD40 ligand interactions plays an important role in T cell
      dependent B cell activation and subsequent differentiation but additional
      interaction structures are also involved in T cell-B cell collaboration.

PMID- 7517972
TI  - Structural analysis of the rat homologue of CD1. Evidence for evolutionary
      conservation of the CD1D class and widespread transcription by rat cells.
AB  - The cDNA encoding the rat homologue of CD1 was isolated and the complete
      nucleotide sequence was determined. It contained an open reading frame of 1008 bp
      that was capable of encoding a polypeptide with 336 amino acids composed of
      hydrophobic leader and transmembrane sequences, three extracellular domains, and
      5' and 3' untranslated sequences. Comparison of the amino acid sequence of rat
      CD1 with those of other species revealed that it showed the highest similarity to
      mouse CD1, which belongs to the CD1D class of the CD1 system and is distinct from
      the classic CD1 class including CD1a, CD1b, and CD1c expressed primarily on human
      thymocytes and some dendritic cells. Widespread transcription of rat CD1 was
      readily detected by Northern blot analysis in nonlymphoid organs, including the
      liver, kidney, and heart, as well as in lymphoid organs, including the thymus,
      lymph node, and spleen. Intestinal expression was also demonstrated by the more
      sensitive reverse transcription-PCR method. Immunoprecipitation with a rabbit
      anti-rat CD1 Ab showed that rat CD1 was expressed on the cell surface as a beta 2
      microglobulin-associated heterodimer. Southern blot analysis of inbred rat
      strains suggested that rat CD1 shows limited polymorphism and that only one CD1
      gene is detectable in the F344 rat genome. These results provide evidence for the
      conservation of CD1D class through mammalian evolution and an apparent lack of
      the classic CD1 class genes in rodents. Functional similarity of rodent CD1 is
      implied.

PMID- 7517973
TI  - A V lambda x-bearing monoclonal antibody with similar specificity and sequence to
      encephalitogenic T cell receptors.
AB  - The fine specificity of mAb F28C4 to myelin basic protein (MBP), acetyl residues
      1-9, has been compared with the previously described specificity of an
      encephalitogenic T cell clone, PJR-25. F28C4 has been found to express a cross
      reactive idiotope (CRI) that is shared with MBP acetyl peptide 1-9-specific TCR.
      The CRI seems to be located at or near the Ag-combining site of F28C4 and the TCR
      and, thus, might possibly result from overlapping epitope specificity. We tested
      the fine epitope specificity of F28C4 by using alanine-substituted peptide
      analogues and found that residues critical for TCR recognition, Cln3 and Pro6,
      are also necessary for F28C4 recognition. By using nuclear magnetic resonance, we
      found that the MBP acetyl peptide 1-9 binds F28C4 in an extended conformation and
      that the central residues are more tightly bound than the terminal residues, much
      like the MBP-TCR interaction. Furthermore, sequence homology (75% overall) was
      found between the regions that contained CDR3 of F28C4 VL and VH and the VDJ
      junction of the TCR V beta. This homology is not shared by other Ig CDR3 regions
      and arises, in part, because F28C4 uses an unusual V lambda light chain, V lambda
      x. Thus, F28C4 shares a CRI with the TCRs, possibly as a result of having similar
      fine epitope specificity and sequence homology. The anti-CRI mAb can down
      modulate experimental allergic encephalomyelitis; thus, it is possible that Abs
      that are similar to F28C4 may play an important immunoregulatory role in
      experimental allergic encephalomyelitis in vivo.

PMID- 7517974
TI  - Partial purification of murine tumor-associated peptide epitopes common to
      histologically distinct tumors, melanoma and sarcoma, that are presented by H-2Kb
      molecules and recognized by CD8+ tumor-infiltrating lymphocytes.
AB  - The B16/BL6 melanoma is a relatively nonimmunogenic tumor expressing low levels
      of MHC class I molecules. BL6 clones expressing transfected H-2Kb class I
      molecules were, by contrast, highly immunogenic in immunocompetent mice. Tumor
      infiltrating lymphocytes (TILs) generated from the H-2Kb+ BL6 lesions (Thy 1.2+,
      CD8+, CD4-) efficiently lysed H-2Kb+ melanoma (CL8-1 and 2Kb38) and the H-2Kb+
      nonrelated 3-methylcholanthrene (MCA)-105 sarcoma, but not the H-2Kb- parental
      melanoma BL6-8. This strongly suggests that CL8-1, 2Kb38, and MCA-105 express
      identical or cross-reactive T cell epitopes recognized by CL8-1 TILs in the
      context of the H-2Kb class I allele. To identify the T cell epitopes, peptides
      were acid-eluted from various cells, and fractionated by HPLC. Five HPLC
      fractions (F1mel-F5mel) of 70 tested contained peptides derived from H-2Kb+ CL8-1
      melanoma (but not H-2Kb- melanomas) that were capable of conferring
      susceptibility to CL8-1 TIL lysis on H-2b-expressing target cells (EL4, C1R.Kb),
      but not on H-2d-expressing P815 target cells. CL8-1 TILs failed to recognize
      peptides derived from H-2Kb+ nonmelanoma targets such as EL4 or normal B6
      splenocytes. Interestingly, CL8-1 TILs appeared to recognize peptide species
      contained in two HPLC fractions derived from the MCA-105 sarcoma (F1sar and
      F5sar). Conversely, TILs derived from MCA-105 lesions recognized MCA-105 and CL8
      1 tumor cells, as well as F5mel and F5sar peptides presented by EL4 targets.
      These data support common murine tumor-associated peptide epitopes presented by H
      2Kb and recognized by CD8+ CTLs derived from histologically distinct tumors,
      melanoma and sarcoma.

PMID- 7517975
TI  - Expression of functional B7 and CTLA4 on rheumatoid synovial T cells.
AB  - To assess the role of B7, CTLA4, and CD28 in the pathogenesis of chronic
      synovitis we analyzed the expression and function of these cell surface molecules
      in patients with rheumatoid arthritis, osteoarthritis, and psoriatic arthritis,
      and in normal controls. Immunoperoxidase staining of rheumatoid synovial
      membranes showed reactivity of 30% of T cells with anti-B7 mAb, in contrast to
      osteoarthritic and normal synovial membranes, in which no such staining was seen.
      In addition, rheumatoid synovial fluid T cells were positive by flow cytometric
      analysis for B7 (mean 20%, range 0 to 96%), as measured by staining with anti-B7
      mAb or the CTLA4 Ig fusion protein, whereas no B7 expression was detected on
      peripheral blood T cells (mean 1%). To analyze the functional importance of B7
      expressed on synovial fluid T cells, we used these cells as stimulator cells in
      primary allogeneic MLC. Purified synovial fluid T cells were far stronger
      stimulator cells compared with paired peripheral blood T cells and resulted in a
      fivefold greater increase in allogeneic T cell proliferation. Furthermore, the
      proliferation induced by purified synovial T cells was markedly inhibited by
      addition of the CTLA4 Ig fusion protein (77%). Moreover, anti-B7 mAb (37%), anti
      CTLA4 mAb (33%), and Fab fragments of anti-CD28 mAb (52%) partially inhibited the
      primary MLC. The expression of functional B7, together with the increased
      expression of MHC class II molecules, indicates that synovial T cells may serve
      as functional APCs and may be capable of autocrine stimulation via the CD28
      activation pathway.

PMID- 7517976
TI  - Dual stimulatory and inhibitory effect of NK cell stimulatory factor/IL-12 on
      human hematopoiesis.
AB  - NK cell stimulatory factor, or IL-12 (NKSF/IL-12), is a heterodimeric cytokine
      produced by monocyte-macrophages, B cells, and possibly other accessory cell
      types. Although the major biologic effects of NKSF/IL-12 have been demonstrated
      on mature T and NK cells, in which it induces cytokine secretion, increased
      cytotoxicity, and proliferation, recent evidence in the murine system has
      suggested that NKSF/IL-12 may play a role in the differentiation of early
      lymphohematopoietic progenitor cells and thymocytes. In this paper, we have
      analyzed the effect of human rNKSF/IL-12 on the formation of colonies by highly
      enriched hematopoietic progenitor cells from human peripheral blood and bone
      marrow. At concentrations between 1 and 10 ng/ml, NKSF/IL-12 synergizes with a
      combination of steel factor and IL-3 to induce formation of mixed, erythroid, and
      myeloid colonies. Therefore, human NKSF/IL-12, like murine NKSF/IL-12, seems to
      belong to a small group of early acting cytokines, including IL-6, granulocyte
      CSF, leukemia-inhibitory factor, and IL-11, which are able to synergize with
      steel factor and IL-3 to induce proliferation and differentiation of very early
      hematopoietic progenitor cells. However, in the presence of enriched preparations
      of NK cells cultured together with the progenitor cells, NKSF/IL-12 inhibits
      formation of hematopoietic colonies supported by IL-3 and granulocyte-macrophage
      CSF, by inducing production of IFN-gamma and TNF-alpha, two cytokines with
      synergistic inhibitory effects on hematopoietic colony formation. Because cell
      types that are able to produce NKSF/IL-12 are present in normal bone marrow and
      NKSF/IL-12 production in vivo and can be stimulated during bacterial or parasitic
      infection, it is possible that the direct stimulatory effect of NKSF/IL-12 on
      hematopoietic progenitor cells and the indirect inhibitory effect mediated by
      secondary cytokine production by lymphoid cells may play a role in the regulation
      of physiologic hematopoiesis and in its alterations during infection.

PMID- 7517977
TI  - Limited T cell response to donor MHC peptides during allograft rejection.
      Implications for selective immune therapy in transplantation.
AB  - Previously, we have demonstrated that during allograft rejection, MHC molecules
      of the donor are processed and presented to alloreactive CD4+ T lymphocytes in
      the form of peptides associated with the MHC class II molecules of the recipient.
      There is an increasing body of evidence that this indirect pathway of
      allorecognition may play a major role in allograft rejection. Herein, we have
      used a series of overlapping MHC peptides progressing along the sequence of the
      donor MHC molecule in single residue steps. We have mapped all potential MHC Ag
      determinants to which T cell responses could be generated after s.c. injection of
      allogeneic splenocytes. We have shown that splenic T cell proliferative responses
      to the beta 1 domains of donor Ak, Ad, and A(s) mouse MHC class II molecules were
      directed toward a single immunodominant determinant in each of three
      donor/recipient combinations. Interestingly, after allogeneic spleen cell
      transplantation, an additional determinant on donor MHC could be detected in the
      draining lymph nodes. This result shows that the fine specificity of T cell
      response to donor transplantation Ags can differ between lymphoid organs. Then,
      we investigated whether limitation of T cell response to donor MHC peptides
      applies to the clinical situation of a graft. We have shown that after an
      allogeneic skin graft, self-restricted alloreactive T cells proliferated to the
      same determinant on the donor MHC molecule. These results indicate that immune
      intervention, such as tolerance induction to the dominant T cell determinant on
      donor MHC molecules, may be developed for the prevention of allograft rejection.

PMID- 7517978
TI  - Engagement of CD14 on monocytes inhibits the synthesis of human Igs, including
      IgE.
AB  - Engagement of CD14 on normal human monocytes results in monocyte activation and,
      furthermore, delivers a negative signal that terminates T cell proliferation. We
      show herein that engagement of selected CD14 epitopes by specific mAbs inhibited
      PWM-induced IgM and IgG synthesis, as well as IL-4-dependent IgE synthesis by
      human PBMCs. Inhibition by anti-CD14 mAb was still evident when the Ab was added
      after 6 days of culture, suggesting that inhibition targets a late B cell
      activation event. In experiments that focused on the role of CD14 in IgE
      regulation, suppression of IgE synthesis after CD14 engagement did not result
      from the release of inhibitory monokines (IL-10, TGF-beta, and PG). In fact,
      neutralizing Abs and specific inhibitors did not restore the IgE response and
      anti-CD14-conditioned monocyte supernatants did not inhibit IgE synthesis. On the
      other hand, inhibition of IgE synthesis by anti-CD14 mAb was not likely to be
      caused by the lack of soluble factors with amplificatory effects on the IgE
      response, because addition of either rIL-6 or rTNF-alpha did not overcome CD14
      dependent inhibition of IgE production. IgE inhibition after CD14 engagement was
      exerted at the B cell level, inasmuch as it was observed not only in T cell
      dependent IgE induction i.e., mononuclear cells stimulated with IL-4, but also in
      T cell-independent systems, i.e., T cell-depleted populations stimulated with IL
      4 plus anti-CD40 mAb or IL-4 plus hydrocortisone. These data indicate that CD14
      plays a regulatory role in B cell responses.

PMID- 7517979
TI  - Distribution of constitutive nitric oxide synthase immunoreactivity and NADPH
      diaphorase activity in murine telogen and anagen skin.
AB  - The freely diffusible radical nitric oxide is generated by nitric oxide synthase,
      and is a pleiotropic, bioregulatory molecule that regulates, e.g., the vascular
      tone, functions as a major neurotransmitter, and is involved in macrophage
      mediated cytotoxicity and platelet aggregation. Constitutive nitric oxide
      synthase exhibits NADPH-diaphorase activity that can be demonstrated
      histochemically. To study whether this enzyme is present in mammalian skin during
      distinct phases of the murine hair cycle, we have examined cryosections of C 57
      BL-6 mouse skin in telogen and depilation-induced anagen VI. Histochemical
      analysis of NADPH-diaphorase activity was complemented by immunohistology, using
      two specific rabbit antisera against constitutive neuronal nitric oxide synthase.
      Epidermis and the outer root sheath showed both immunoreactivity for the enzyme
      and NADPH-diaphorase activity, whereas dermal papilla and sebaceous glands
      displayed only strong NADPH-diaphorase activity, suggesting that this enzyme
      histochemical test measures additional enzymes besides nitric oxide synthase.
      Intrinsic nitric oxide synthase immunoreactivity was also detected by immunoblot
      in mouse skin homogenates, staining proteins of an apparent 160-kDa molecular
      weight. Compared to telogen skin, these immunoreactive proteins were
      quantitatively increased in anagen VI skin. Thus, our study suggests that defined
      epithelial compartments of normal murine skin are capable of synthesizing nitric
      oxide and that the molecule may be involved in skin physiology, growth, and
      remodeling.

PMID- 7517980
TI  - Selective upregulation of intercellular adhesion molecule (ICAM-1) by ultraviolet
      B in human dermal microvascular endothelial cells.
AB  - Although a portion of ultraviolet light (UV) penetrates into the dermis,
      histologic changes that occur within the dermal microvasculature have largely
      been attributed to the elaboration of biologic substances, such as interleukin 1
      (IL-1), from other constitutive cells of the skin, as opposed to a direct effect
      of UV on the endothelial cell. As a potential model for understanding early
      molecular events occurring in UV-induced cutaneous inflammation, we have examined
      the direct effects of UVB, as well as cytokine-positive controls, upon human
      dermal microvascular endothelial cells (HDMEC) cell adhesion molecule (CAM) gene
      expression. Cultured HDMEC were exposed to varying dosages of UVB, and examined
      for cell surface and mRNA expression of the CAMs intercellular adhesion molecule
      1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin (formerly
      ELAM-1). Following UVB exposure, dose-dependent increases in baseline cell
      surface expression of ICAM-1 were demonstrated by fluorescence-activated cell
      sorter analysis with concomitant increases in ICAM-1 mRNA, as shown by Northern
      blot analysis; there was no induction of either E-selectin or VCAM-1. The UVB
      induced ICAM-1 upregulation could not be blocked by antibodies to IL-1 or tumor
      necrosis factor alpha (TNF-alpha). In fact, ICAM-1 gene regulatory region based
      CAT reporter gene plasmids, including constructs containing IL-1- and TNF-alpha
      responsive elements, did not display increased CAT expression after transfection
      into HDMEC followed by UVB exposure, though control cytokine-treated
      transfectants did. Thus, UVB selectively upregulates ICAM-1, but not E-selectin
      or VCAM-1, mRNA and cell surface expression in HDMEC, and this upregulation is
      not dependent upon the autologous secretion and activity of either IL-1 or TNF
      alpha.

PMID- 7517981
TI  - Immunosuppressive effects of azelastine hydrochloride on contact hypersensitivity
      and T-cell proliferative response: a comparative study with FK-506.
AB  - Azelastine hydrochloride (AZE) is an anti-allergic drug that inhibits the release
      of various chemical mediators from mast cells. We compared the immunosuppressive
      effects of AZE and FK-506 in vivo and in vitro. Topical application of AZE
      strongly inhibited the efferent phase of contact hypersensitivity, as did
      application of FK-506. In in vitro experiments, we found that 1) the suppression
      by AZE on interleukin (IL)-2 production from splenic T cells was partial and
      considerably large amounts of IL-2 were still produced, even in the presence of
      10(-5) M of AZE, which was in sharp contrast to the observed marked inhibition of
      [3H]-TdR incorporation; 2) AZE significantly inhibited the phorbol myristate
      acetate-induced IL-2 responsiveness; 3) AZE did not inhibit the IL-2 receptor
      alpha expression of activated T cells; and 4) the significant inhibitory action
      was still observed even when AZE was added at 48 h after the initiation of
      culture. In regard to FK-506, we found that 1) FK-506 completely blocked the
      production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced
      inhibition; 3) FK-506 affected the phorbol myristate acetate-induced IL-2
      responsiveness very little, if any; and 4) the significant suppression was
      observed only when FK-506 was added within 24 h after the initiation of culture.
      Thus, AZE exerts its in vitro immunosuppressive activity preferentially by
      interfering with the IL-2 responsiveness, with partial inhibition of IL-2
      production. Conversely, FK-506 acts as a strong inhibitor of IL-2 production
      without a prominent effect on IL-2 responsiveness. The immunosuppressive activity
      of AZE shown in vitro may also be operative in vivo and may be applicable for
      topical use.

PMID- 7517982
TI  - Expression of B7 costimulatory molecule in cultured human epidermal Langerhans
      cells is regulated at the mRNA level.
AB  - Langerhans cells (LC) belong to the dendritic cell lineage and are the principal
      antigen-presenting cells of squamous epithelia. Short-term cultured LC (cLC)
      exhibit a marked augmented capacity to stimulate allogeneic T cells and acquire
      the ability to activate naive T cells, probably in relation to enhanced
      expression of accessory signals. In this study, we evaluated the expression of B7
      costimulatory molecule (CD80) in human freshly isolated (fLC) and cLC at both the
      protein and mRNA level. Staining of frozen skin sections did not reveal any
      epidermal dendritic cell reactive with either of two different anti-B7 monoclonal
      antibodies. fLC in suspension did not exhibit any B7 staining as evaluated by two
      color flow-cytometry analysis and immunoelectron microscopy. In contrast, LC that
      were cultured for 24-72 h displayed strong surface B7 reactivity with a
      characteristic patchy pattern. Treatment with dispase and trypsin did not reduce
      B7 staining of cLC. Following warming to 37 degrees C, cLC tagged with anti-B7
      monoclonal antibody and gold-conjugated secondary antibody could internalize
      surface B7 by using the organelles of receptor-mediated endocytosis. B7 mRNA,
      detected by the reverse-transcriptase polymerase chain reaction technique, was
      expressed at a low level in purified (> 90% HLA-DR+) fLC but not in LC-depleted
      epidermal cells, and was markedly upregulated in purified cLC. The results
      indicate that 1) fLC do not express B7 protein on their surface, but acquire B7
      during culture, 2) surface B7 is not sensitive to trypsin, 3) B7 expression is
      regulated primarily at the mRNA level, and 4) membrane B7 can be internalized
      within cLC. B7 molecule on CLC may be relevant to their increased antigen
      presenting cell potency and ability to stimulate naive T lymphocytes.

PMID- 7517983
TI  - Peripheral blood mononuclear cells from patients with bullous pemphigoid have an
      increased frequency of response to synthetic peptides encoded by BPAG1.
AB  - We determined the response of peripheral blood mononuclear cells from patients
      with bullous pemphigoid and normal subjects to synthetic peptides encoded by
      BPAG1. Peripheral blood mononuclear cells from patients and normal subjects were
      cocultured in the presence of 15-22-amino-acid-long amphipathic and hydrophilic
      peptides selected from the BPAG1 sequence. Seven of 10 patients (70%) with
      bullous pemphigoid had an increased response of peripheral blood mononuclear
      cells (> 3.25/10(6) cells) when cultured with amphipathic sequences encoded by
      BPAG1 compared to 3 of 10 (30%) normal subjects. Peripheral blood mononuclear
      cells from 3 of 15 (20%) patients and 3 of 15 normal subjects (20%) demonstrated
      an increased response when cultured with hydrophilic peptides. Peptides
      associated with an increased peripheral blood mononuclear cell response in
      patients with bullous pemphigoid were adjacent to regions of BPAG1 recently
      demonstrated to contain epitopes recognized by circulating autoantibodies in the
      sera of patients with bullous pemphigoid. Increased peripheral blood mononuclear
      cell responses were more commonly observed in patients with bullous pemphigoid
      with generalized disease and those who had their disease for longer than 2 months
      (p < 0.05). The observation that increased duration and generalized disease was
      associated with increased peripheral blood mononuclear cell responses to peptides
      encoded by BPAG1 supports the hypothesis that responses to BPAG1 may occur as a
      consequence of ongoing inflammation at the basement membrane.

PMID- 7517984
TI  - Three-dimensional model of a human interferon-alpha consensus sequence.
AB  - A computer-built, three-dimensional, atomic-level model for human interferon
      alpha (IFN-alpha) was constructed. This model was prepared using the primary
      amino acid sequence of consensus IFN-alpha (IFN-alpha Con1) and the alpha-carbon
      Cartesian coordinates of murine IFN-beta as a homolog guide to the model
      building. In agreement with an earlier report from this laboratory, the two
      domains 29-35 and 123-140 are in close spatial proximity in this model, and may
      constitute a receptor recognition domain, whereas the region bounded by residues
      78-95 is somewhat removed from this region on the molecule and may constitute an
      alternative active site. Extrapolating from the model, we propose that, of the
      stretch 123-140, the residues that are exposed are 123, 125, 126, 128-130, and
      132-139; and of the stretch 29-35, all are accessible. Additionally, we propose
      that there may be sufficient complexity in the Type 1 IFN receptor to account for
      the differential sensitivities between IFN-alpha s and IFN-beta that may be
      associated with residue differences in the region 78-95, specifically at residues
      84, 86, and 87. This model conforms with experimental data that identify specific
      amino acid residues in human IFN-alpha that either do, or do not, affect the
      active conformation and biological activities of the molecule.

PMID- 7517986
TI  - [A simple and rapid confirmation method of the bacterial contamination using
      polymerase chain reaction].
AB  - We studied the method for detection of bacterial contamination. Polymerase chain
      reaction (PCR) was used to amplify the 888 base pair of 16S ribosomal RNA (rRNA)
      gene fragment of various strains of bacterial species. The supernatant of
      bacterial suspension after treatment for 10 min at 100 degrees C was used for a
      template DNA. A total of 151 strains of 16 genus of Gram-negative rod and of one
      genus of Gram-positive cocci were confirmed and were divided into five categories
      by comparing digestion patterns resulting from restriction endonuclease (MluI,
      Eco RI and Hind III) cleavage of target rDNA fragment. These five types, such as
      Shigella spp. and E. coli group (Group I), other nine genera of Enterobacteria
      excluding Group I and Aeromonas spp. (Group II), Vibrio spp. (Group III),
      Campylobacter spp. and P. aeruginosa (Group IV), and S. aureus (Group V), were
      recognized. The group I was digested by three enzymes used, group II was by Mlu I
      and Eco RI but not by Hind III, group III was only by MulI, and group IV was not
      digested with all enzymes. The group V was sensitive to Eco RI and Hind III but
      was resistant to Mlu I. This method is a widely applicable technique for
      detection of bacterial contamination.

PMID- 7517985
TI  - Suppression of mitochondrial mRNA levels and mitochondrial function in cells
      responding to the anticellular action of interferon.
AB  - A lambda cDNA library prepared from polyadenylated RNA isolated from Daudi cells
      was differentially screened to isolate cDNAs that recognize mRNA whose levels are
      reduced following interferon (IFN) treatment. Southern blot and DNA sequence
      analysis of 20 cDNA clones that were isolated revealed that they represented
      mitochondrially encoded mRNAs for the following proteins: cytochrome c oxidase
      subunits II and III, ATPase 6, cytochrome b, and subunit 1 of the NADH
      dehydrogenase. Northern blot analysis employing these cDNAs and oligonucleotides
      generated to the remaining mitochondrially encoded mRNAs demonstrated that IFN
      alpha treatment of Daudi cells mediates a time-dependent suppression of the level
      of all of the mitochondrially encoded mRNAs. Study of this IFN-mediated effect
      reveals that: (i) the suppression of the level of these mRNAs is dependent on
      protein synthesis, (ii) it can be observed to occur prior to any detectable
      effect on thymidine incorporation, (iii) the degree of suppression correlates
      with the sensitivity of the cells to the anticellular action of IFN, and (iv) the
      suppression of the level of these RNAs appears to result from an effect on the
      level of transcription rather than on the stability of these mRNAs. A study of
      the level of cellular respiration in IFN-treated Daudi cells reveals a clear
      suppression 3 h following IFN treatment.

PMID- 7517987
TI  - [Effect of biological response modifiers against pulmonary candidiasis in
      neutropenic mice].
AB  - We investigated the prophylactic and therapeutic effects of biological response
      modifiers (rHG-CSF, M-CSF, rhIL-2) on pulmonary candidiasis in neutropenic mice.
      Cyclophosphamide treated mice were injected by the intratracheal route with 5 x
      10(6) Candida yeast cells. Prophylactic treatment with rhG-CSF afforded
      significant protection against pulmonary candidiasis in neutropenic mice.
      Treatment with rhG-CSF also increased the number of peripheral blood neutrophils.
      The histopathological investigations in our experiments showed that the assembly
      of PMNs to the infected lung at 24 hrs after bacterial challenge was more
      remarkable in the rhG-CSF treated mice than that in the vehicle alone. Number of
      viable candida cells in the infected lung in the rhG-CSF treated mice were
      significantly decreased. The combination of rhG-CSF and fluconazole was more
      effective than those of each monotherapy. Prophylactic treatment with M-CSF or
      rhIL-2 had no influence on pulmonary candidiasis. These results show the
      possibility that rhG-CSF could be of help for treating human deep candidiasis not
      successfully treated with antimicrobial agents alone.

PMID- 7517988
TI  - Clear cell carcinoma arising in a pleomorphic adenoma of the submandibular gland.
AB  - Clear cell carcinoma of salivary gland is a rare neoplasm. We report a third case
      of clear cell carcinoma arising in a pleomorphic adenoma and also in an
      extraparotid location. We document the immunohistochemical profile of the tumour
      including reactivity with a marker for the c-erbB-2 oncoprotein and suggest a
      myoepithelial origin for these lesions. The presence of a tetraploid stemline may
      account for the rapid tumour progression in this case.

PMID- 7517989
TI  - The CD14 differentiation antigen mediates the development of endotoxin
      responsiveness during differentiation of mononuclear phagocytes.
AB  - The CD14 antigen was originally described as a differentiation antigen on
      mononuclear cells. The purpose of this study was to investigate the relationship
      between the appearance of surface CD14 and the acquisition of lipopolysaccharide
      (LPS) responsiveness during maturation of mononuclear phagocytes. Immature THP-1
      cells responded poorly to LPS in the absence or presence of serum. Treatment with
      the maturational agent calcitriol caused a dose- and time-dependent increase in
      CD14 mRNA and surface CD14 and enhanced the responsiveness of THP-1 cells to
      smooth and rough form LPS, complexes of LPS and lipopolysaccharide-binding
      protein (LBP), and LPS in low concentrations of serum. Monoclonal antibodies to
      CD14 blocked the responses of THP-1 to LPS, LPS-LBP complexes and LPS in serum.
      Immunodepletion of LBP from serum also inhibited the effect of LPS in serum. The
      data show that maturation of the response of THP-1 cells to LPS and LPS-LBP
      complexes depends on the appearance of CD14 on the cell surface. Maturation of
      the response to LPS in serum depends in large part on the appearance of CD14 on
      the cell surface and the presence of LBP in serum.

PMID- 7517990
TI  - Changes in subcellular localization and surface expression of L-selectin,
      alkaline phosphatase, and Mac-1 in human neutrophils during stimulation with
      inflammatory mediators.
AB  - The localization of the adhesion protein L-selectin in human neutrophils was
      determined by subcellular fractionation and immunoelectron microscopy and
      compared with the localization of Mac-1 (alpha m beta 2) and alkaline
      phosphatase, the marker for secretory vesicles. L-selectin was found to be
      localized exclusively on the plasma membrane of unstimulated cells and also of
      stimulated cells, although markedly diminished. This was in contrast to Mac-1,
      which was also localized in secretory vesicles and in specific/gelatinase
      granules as shown previously [Sengelov, H., et al. J. Clin. Invest. (1993) 92,
      1467-1476]. Stimulation of neutrophils with inflammatory mediators such as tumor
      necrosis factor (TNF), platelet-activating factor (PAF), or f-Met-Leu-Phe (fMLP),
      induced parallel up-regulation of the surface membrane content of alkaline
      phosphatase and Mac-1 and down-regulation of L-selectin, as evidenced by flow
      cytometry. Preimbedding immunoelectron microscopy confirmed that L-selectin was
      present mainly on tips of microvilli in unstimulated cells and showed that
      alkaline phosphatase and Mac-1 were randomly distributed on the surface membrane
      of fMLP-stimulated cells. These studies indicate that the transition of
      neutrophils from L-selectin-presenting cells to Mac-1-presenting cells induced by
      inflammatory mediators is mediated by incorporation of secretory vesicle
      membrane, rich in Mac-1 and devoid of L-selectin, into the plasma membrane.

PMID- 7517992
TI  - PSA screening.

PMID- 7517991
TI  - [Hemorheologic changes in preoperative hemodilution during total hip replacement.
      Randomized study comparing hydroxyethyl starch 200,000/0.62 (HES) and a dextran
      60,000].
AB  - Hemodilution can be used to save blood transfusion during total hip replacement.
      We have carried out a randomized study to compare the hemorheological effects of
      two plasma substitutes: a hydroxyethylstarch 200,000/0.62 versus a dextran
      60,000. Twenty-two patients were hemodiluted with 20 mk/kg of either substitute,
      just after the spinal anesthesia. Whereas the hematocrit have fallen by 30% in
      the two groups, significant differences are observed about hemorheological
      parameters. The plasma viscosity express a greater increase at hour 4 in the
      dextran group. The whole blood viscosities are more increased in the dextran
      group at hour 4 and 24. The erythrocyte aggregation is decreased in the HES group
      at hour 4 and 24, but is increased in the dextran group. The fibrinogen is more
      increased in the dextran group at day 7. In spite of similar hemodilutions, the
      two substitutes express different hemorheological effects with a favourable role
      of HES on erythrocyte aggregation and blood viscosities. This can improve the
      microcirculation and decrease the activation of the endothelial cells, reducing
      the inflammatory reaction.

PMID- 7517993
TI  - Reid's Colposcopic Index.
AB  - Reid's Colposcopic Index (RCI) is a systematic, objective method of
      colposcopically grading the severity of premalignant cervical lesions. The index
      considers four colposcopic signs: lesion margin, color of acetowhitening, blood
      vessels, and iodine staining. The RCI can accurately predict the histologic grade
      of cervical disease, readily permitting differentiation between low-grade
      cervical disease and high-grade disease. Hence, use of the index helps direct the
      clinician to perform a biopsy of the most significant abnormal cervical lesions
      and enhances the formulation of the colposcopic impression.

PMID- 7517994
TI  - Morphological evidence that hypothalamic substance P-containing afferents are
      capable of filtering the signal flow in the monkey hippocampal formation.
AB  - This study in the African green monkey (Cercopithecus aethiops) was designed to
      characterize the neurochemical features of hippocampal nonpyramidal neurons that
      are specific synaptic targets of substance P-containing projective neurons
      located in the supramammillary nucleus. Our previous studies provided evidence
      for an excitatory nature to this hypothalamo-hippocampal pathway and described
      the mode of termination of these afferents on hippocampal principal neurons. The
      present correlated light and electron microscopic immunocytochemical analysis,
      using the nickel-diaminobenzidine/diaminobenzidine double-labeling technique,
      revealed that this hippocampal afferent system establishes multiple, exclusively
      asymmetric synapses with three specific subpopulations of nonpyramidal cells: (1)
      a small portion of parvalbumin-containing basket cells located periodically in or
      adjacent to the granule cell layer of the dentate gyrus, which therefore inhibit
      only a subpopulation of granule cells; (2) some of the calbindin-immunoreactive
      local circuit neurons located in the hilar area; and (3) calbindin-positive cells
      occurring exclusively in the stratum molecular of the middle portion of the CA3
      subfield. Postembedding studies revealed that the aforementioned calbindin
      containing cells are GABAergic inhibitory neurons. Our studies indicate that
      hypothalamic afferents can effectively filter the information flow at different
      levels of the excitatory signal loop in the monkey hippocampal formation. Dentate
      granule cells, which are only stimulated by hypothalamic afferents, will transfer
      excitatory signals differently than those that are controlled by a feedforward
      inhibitory mechanism initiated by these fibers. In the CA3 subfield, the signal
      flow can again be depressed by those pyramidal neurons that are inhibited by
      calbindin-containing cells receiving an excitatory hypothalamic input.

PMID- 7517995
TI  - Sodium nitroprusside evokes the release of immunoreactive calcitonin gene-related
      peptide and substance P from dorsal horn slices via nitric oxide-dependent and
      nitric oxide-independent mechanisms.
AB  - The results of behavioral studies suggest that nitric oxide (NO) participates in
      certain spinal mechanisms that contribute to hyperalgesia. Additionally, previous
      studies indicate that the release of immunoreactive calcitonin gene-related
      peptide (iCGRP) and substance P (iSP) is increased in the dorsal horn of the
      spinal cord during hyperalgesia. Therefore, the aim of this study was to
      determine whether NO acts to enhance peptide release in the dorsal horn of rats
      using an in vitro superfusion technique. Sodium nitroprusside (SNP) was used as
      an NO donor. The results of this study indicate that SNP caused a dose-related,
      calcium-dependent increase in the release of iCGRP and iSP from dorsal horn
      slices of the rat spinal cord. Furthermore, pretreatment with SNP reduced the
      ability of capsaicin to evoke the release of either peptide, suggesting that a
      target for SNP exists on certain capsaicin-sensitive primary afferent terminals.
      In addition to increasing peptide release, SNP also caused a significant five to
      sixfold increase in the levels of immunoreactive guanosine 3',5'-monophosphate (i
      cGMP) in the dorsal horn. This SNP-evoked increase was significantly decreased by
      the guanylate cyclase inhibitor methylene blue in a dose-dependent manner. In
      addition, the release of iCGRP was also significantly reduced in the presence of
      methylene blue, although the relationship between peptide release and i-cGMP
      production remains unclear. Sodium nitroprusside-evoked peptide release was
      significantly reduced in the presence of hemoglobin (an oxide radical scavenger),
      suggesting that the drug effect was due to the generation of NO. However, the
      release of iCGRP and iSP was also evoked by sodium ferricyanide (the coproduct of
      SNP) and by 7-d-old, photoinactivated SNP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7517997
TI  - Distribution of carbohydrate epitopes among disjoint subsets of leech sensory
      afferent neurons.
AB  - Carbohydrate recognition plays an important role in the development of normal
      projections of sensory afferent neurons in the leech CNS. Four different
      carbohydrate epitopes are expressed by sensory afferents on their 130 kDa surface
      proteins: all sensory afferents share a common carbohydrate epitope (CE0) that
      helps them to enter and project diffusely across the synaptic neuropil; a
      restricted expression of three other carbohydrate epitopes (CE1, CE2, and CE3)
      serves to distinguish three subsets of sensory afferents. We examined the subsets
      of sensory afferents defined by their subset carbohydrate epitopes in the leech
      lip, skin, gut, and CNS. We established that the CE1, CE2, and CE3 subset
      epitopes define disjoint subsets of neurons by double labeling sensory afferents
      with monoclonal antibodies for different pairs of subset epitopes. We found that
      CE2 and CE3 afferents populate the lip and skin, but not the gut, and that these
      two subsets of sensory afferents have convergent projection patterns in the CNS.
      We found that CE1 afferents populate the gut and skin, but not lips; furthermore,
      their CNS projections diverge from those of CE2 and CE3 afferents. Our data fit
      the hypothesis that these carbohydrate epitopes are related to sensory modality
      of afferent subsets.

PMID- 7517998
TI  - Vascularization and microvascular permeability in solid versus cell-suspension
      embryonic neural grafts.
AB  - Vascularization and microvascular permeability were assessed in a comparative
      study of solid (organized) and cell-suspension (dissociated) fetal nigral grafts
      implanted in the dopamine-deprived striatum of adult rats. Both graft types were
      analyzed by chromogen detection of intravenously injected horseradish peroxidase
      (HRP), which outlined vessel walls, and, in cases in which the blood-brain
      barrier was compromised, permeated the graft and host parenchyma. Survival of
      graft-derived dopaminergic cells was assessed using tyrosine hydroxylase (TH)
      immunocytochemistry. Glial reactivity to cell-suspension grafts was similarly
      assessed with an antibody directed against glial fibrillary acidic protein.
      Morphometry revealed significantly higher microvessel density in the cell
      suspension grafts (p < 0.001), which effectively equaled that found in the
      contralateral striatum despite rather prominent surrounding glial reactivity.
      Capillaries in the cell-suspension grafts were not permeable to blood-borne HRP
      at postimplantation study times of 7, 14, and 30 days whereas, in the solid
      grafts, permeability in some cases could be detected for up to 30 days. Large
      numbers of cells immunoreactive for TH were seen in cell-suspension grafts; in
      contrast, few if any were found in the majority of solid transplants. The
      multiple-fragment solid graft implant model used clinically compares poorly with
      the cell-suspension model because it lacks consistency in early revascularization
      and shows a greater (albeit temporary) tendency for blood-brain barrier
      dysfunction. Delayed and inadequate vascularization of the solid graft is likely
      to account for graft failure more often than in the cell-suspension graft.
      Similarly, a certain critical number of specific grafted cells are required to
      achieve sufficient expression to bring about a favorable response in the disabled
      host, and this expression appears to be achieved less consistently with the solid
      implant technique.

PMID- 7517996
TI  - Activation of metabotropic glutamate receptors differentially affects two classes
      of hippocampal interneurons and potentiates excitatory synaptic transmission.
AB  - Based on responses to metabotropic glutamate receptor (mGluR) activation, we have
      characterized two distinct classes of interneuron in stratum (st.) oriens of the
      CA1 region of hippocampus. One type of interneuron was strongly excited by 1S,3R
      aminocyclopentane dicarboxylic acid (ACPD), responding with a large inward
      current accompanied by increased baseline noise and prominent current
      oscillations. A second interneuron population responded with a modest inward
      current with no changes in baseline noise. These two classes of responses
      persisted in the presence of tetrodotoxin and antagonists of ionotropic glutamate
      and GABA receptors, suggesting that the inward currents result from mGluRs on the
      interneurons themselves. The two physiologically defined cell types correspond to
      two distinct morphological cell types in st. oriens/alveus, distinguished by very
      different patterns of local axonal connections. Large oscillatory inward current
      responses were recorded predominantly from an interneuron type whose axons
      heavily innervated st. lacunosum. The more modest inward current response was
      generally found in interneurons whose axons innervated the somata and proximal
      dendrites of CA1 pyramidal neurons. These differences in physiology and local
      circuitry imply that activation of mGluRs in st. oriens will cause very strong
      excitation of interneurons synapsing in st. lacunosum, and weaker excitation of
      interneurons innervating pyramidal cells at the soma and proximal dendrites.
      These data suggest that each interneuron population has a specific role in
      hippocampal function, and that mGluR activation will affect the local circuit
      differently for each interneuron type. Metabotropic GluR activation also markedly
      enhanced the amplitudes of the evoked and spontaneous EPSCs received by all
      interneurons in the region, independent of changes in the postsynaptic holding
      current and with no change in the kinetics of the EPSC. In contrast to the
      enhancement of evoked and spontaneous EPSCs, miniature EPSCs recorded in the
      presence of tetrodotoxin were not increased. These data suggest that ACPD acts at
      a presynaptic site to potentiate the EPSC. Taken together, these results
      highlight an important modulatory role for metabotropic receptors located at
      sites both pre- and postsynaptic to CA1 st. oriens interneurons.

PMID- 7517999
TI  - Nursing care for children with developmental disabilities in Israel, Part II:
      Programs illustrating the expanding role of the nurse.

PMID- 7518000
TI  - Correlates of cognitive development in low-birth-weight infants from low-income
      families.
AB  - A descriptive correlational design was used to investigate the relationship
      between environmental and perinatal variables and cognitive development in a
      sample of 30 low-birth-weight (LBW) preterm infants from low-income families. The
      incidence of mental or gross motor delay in this convenience sample was 20% (n =
      6). Quality of home environment (Home Observation for Measurement of the
      Environment, Caldwell & Bradley, 1984) was significantly correlated with
      cognitive development as measured by the Bayley Scales of Mental Development
      (Mental Development Index [MDI]) (r = .54, p = 0.002). The HOME score predicted
      29% of the variance (beta = .542, p = 0.002) in MDI scores. Birth weight and
      maternal education level were not significantly correlated with cognitive
      development in this sample. The correlation between the level of maternal
      depressive symptoms and the MDI scores of the infants approached significance at
      the p = 0.05 level, (r = -.35, p = 0.055). These findings demonstrate that the
      home environment is significant to developmental outcomes in high-risk infants.
      Implications for further research and nursing practice are discussed.

PMID- 7518001
TI  - Approaches toward selective inhibition of nitric oxide synthase.

PMID- 7518002
TI  - Studies on neurokinin antagonists. 4. Synthesis and structure-activity
      relationships of novel dipeptide substance P antagonists: N2-[(4R)-4-hydroxy-1
      [(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl]-N- methyl-N-(phenylmethyl)-3-(2
      naphthyl)-L-alaninamide and its related compounds.
AB  - As an extension of our studies on discovering a novel substance P (SP)
      antagonist, we modified the previously reported dipeptide, N2-[N2-(1H-indol-3
      ylcarbonyl)-L-lysyl]-N-methyl-N-(phenyl-methyl) -L- phenylalaninamide (2b). The
      lysine part in 2b was first optimized to a (2S,4R)-hydroxyproline derivative
      (3h), which is 2-fold more potent than 2b in [3H]SP binding assay using guinea
      pig lung membranes. Next we modified the 1H-indol-3-ylcarbonyl part in 3h.
      Introduction of a methyl group at the indole nitrogen enhanced the oral activity,
      while retaining the binding activity. Finally, we modified the phenylalanine part
      to culminate in the most potent compound 7k (FK888), which is a potent SP
      antagonist with NK1 selectivity as well as oral activity.

PMID- 7518004
TI  - Proteolipid protein interactions in transfectants: implications for myelin
      assembly.
AB  - The proteolipid proteins (PLP and DM20) are major constituents of CNS myelin, but
      how they are delivered to and organized within the oligodendrocyte plasma
      membrane is incompletely understood. We have expressed both PLP and DM20 singly
      or together in a host cell line, HeLa. In either DM20 or PLP transfectants, at
      early time points (24 hours), the expressed proteins are found within
      intracellular compartments. In DM20 transfectants, the protein is delivered to
      the plasma membrane by 48 hours. In HeLa cells, PLP remains intracellular when
      expressed in the absence of DM20; only when it is coexpressed with DM20 is it
      transported to the plasma membrane. In cotransfectants, PLP can also be localized
      to organelles involved in both the protein biosynthetic and the endocytic
      pathways. Since, in HeLa cells at least, the delivery of PLP to the plasma
      membrane is facilitated by the coexpression of DM20, we suggest that the two
      proteins interact intracellularly to form a complex. In some PLP/DM20
      cotransfectants, the proteolipids are concentrated in regions of cell-cell
      contact. The regional accumulation of these proteins at cell-cell interfaces is
      highly reminiscent of the behavior in transfected cells of another myelin
      protein, P0, and certain cadherin polypeptides, both of which have readily
      demonstrable membrane adhesive properties. Our data suggests that at certain
      stoichiometric ratios, proteolipids can become stabilized at cell surfaces to
      form adhesive bonds.

PMID- 7518006
TI  - Many naturally occurring mutations of myelin proteolipid protein impair its
      intracellular transport.
AB  - The primary structure of the proteolipid protein (PLP) from the central nervous
      system (CNS) myelin of mammals is highly conserved with only three amino acid
      differences between the mouse, rat, dog, bovine, and human proteins. Furthermore,
      within a particular species no polymorphisms in the protein have been identified.
      Recent interest has focused on the targeting of PLP in oligodendrocytes and the
      role that mutant forms of this protein play in generating dysmyelinating or
      hypomyelinating diseases. We previously expressed the human cDNA encoding PLP in
      transiently transfected Cos-7 cells and characterized the subcellular
      distribution of the protein in this simple heterologous system. In the current
      study we have used the same paradigm to examine the effect of five missense
      mutations in the PLP gene on processing of the encoded protein. The mutations
      chosen span the carboxy-terminal half of PLP and encompass that part of the
      protein in which most mutations have been identified. Our results show that
      transport of all mutations examined was arrested in the secretory pathway at an
      early stage, causing the mutant proteins to accumulate in the endoplasmic
      reticulum. Thus, a common mechanism of protein misfolding and failure of PLP to
      reach the cell surface of oligodendrocytes rather than the inability of the
      mutant protein to perform some crucial function at the cell surface may be
      responsible for the diseases caused by many PLP mutations. Our results, together
      with those of others, prompt us to speculate that the pathobiology observed in
      PLP mutants may result from oligodendrocyte cell death caused by the accumulation
      of misfolded protein in the endoplasmic reticulum. This speculation is consistent
      with the observations that oligodendrocytes bearing misfolded PLP, as in the
      jimpy mutant, proliferate but die rapidly while oligodendrocytes from PLP
      deletion survive and produce a myelin-like membrane which lacks PLP.

PMID- 7518005
TI  - Intracellular transport and sorting of the oligodendrocyte transmembrane
      proteolipid protein.
AB  - Delineating the properties and functions of the major central nervous system
      myelin proteins has been the focus of intensive research for decades. For PLP,
      this task has been confounded by its unusual properties, the complexity of the
      cellular membrane in which it resides, and the absence of a functional assay for
      the protein. The development of new experimental paradigms in which to study PLP
      may shed fresh light on the properties and functions of this intrinsic membrane
      protein. In the present communication we have used indirect, double label,
      immunofluorescence, and confocal microscopy to examine the distribution of PLP in
      Cos-7 cells transfected with an expression vector bearing the human PLP cDNA. Our
      results show that PLP is synthesized in the rough endoplasmic reticulum of
      transfected cells and passes through the Golgi apparatus to the cell surface.
      These results are consistent with previous studies showing PLP reaches the cell
      surface by transport through the secretory pathway. Levels of PLP at the cell
      surface are modest, most likely because protein deposited in this compartment can
      be endocytosed and subsequently transported to perinuclear lysosomes. Similar
      results are reported in the companion communication by Sinoway et al. (J Neurosci
      Res, 37:551-562, 1994). Using transfected HeLa cells they show that DM20 alone
      and PLP coexpressed with DM20 assume appropriate conformations for transport to
      the cell surface. The presence of PLP in subcellular compartments beyond the
      endoplasmic reticulum in Cos-7 cells indicates that the protein achieves a
      conformation appropriate for transport in the absence of other oligodendrocyte
      specific factors; however, accumulation of large amounts of PLP in the
      cytoplasmic membrane compartment may require interactions with such glial
      specific factors. Thus, the transfection paradigm described herein should prove a
      useful tool for investigating the folding and sorting of wild type and mutant
      forms of PLP as well as its membrane topology and posttranslational processing.

PMID- 7518003
TI  - 12(S)-HETE enhancement of prostate tumor cell invasion: selective role of PKC
      alpha.
AB  - BACKGROUND: Prostate carcinoma has become the second most fatal cancer in
      American men. In Dunning R3327 rat prostate adenocarcinoma cells, elevated
      invasiveness positively correlates with metastatic potential. However, the
      mechanism(s) responsible for regulation of tumor cell motility and invasion is
      poorly understood. We have reported that a lipoxygenase metabolite of arachidonic
      acid, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], augments tumor cell
      metastatic potential through activation of protein kinase C (PKC). PURPOSE: We
      proposed to determine the effect of 12(S)-HETE on the motility and invasion of
      low-metastatic rat prostate AT2.1 tumor cells and the effect of 12(S)-HETE
      activation of specific PKC isoform(s) in these processes. METHODS: The motility
      of AT2.1 cells was determined by the colloidal gold phagokinetic track assay and
      the invasiveness measured as their ability to invade through basement membrane
      Matrigel-coated filters. Expression of PKC isoforms was determined by Western
      blotting of the whole cell lysate with isoform-specific anti-PKC antibodies.
      Cytosol and membrane fractions were prepared and the subcellular distribution of
      PKC was analyzed by Western blotting and activity assay. The effect of 12(S)-HETE
      on cell proliferation was examined. Data were analyzed for significance of
      difference with the two-sampled, two-sided Student's t test. RESULTS: 12(S)-HETE
      increased the motility and invasion of AT2.1 cells, and this 12(S)-HETE-increased
      motility and invasion were inhibited by a selective PKC inhibitor, calphostin C,
      as well as a Ca2 chelator, bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid/tetra(acetoxy-methyl)ester. AT2.1 cells expressed the PKC isoforms alpha and
      delta, and 12(S)-HETE increased the membrane association of PKC alpha but not
      delta. Further, the motility and invasion of AT2.1 cells were increased by
      thymelea toxin, a selective activator of PKC alpha over PKC delta. CONCLUSION:
      12(S)-HETE augments the invasiveness of AT2.1 cells via selective activation of
      PKC alpha. IMPLICATIONS: 12(S)-HETE modulation of PKC alpha invasiveness may be
      an important mechanism of action for the regulation of the invasive potential of
      rat prostate carcinoma cells, and the 12-lipoxygenase enzyme and/or PKC alpha may
      serve as key targets for the development of anti-invasive agents useful for
      combating the spread of prostate cancer.

PMID- 7518007
TI  - Axotomy induces preprotachykinin gene expression in a subpopulation of dorsal
      root ganglion neurons.
AB  - The distribution of dorsal root ganglion (DRG) cell sizes that show changes in
      preprotachykinin (PPT) gene expression and substance P (SP) levels following
      axotomy was examined using RNA blot analysis, in situ hybridization
      histochemistry, and immunocytochemistry. PPT mRNA was induced in medium-sized
      (1,000-2,000 microns 2) and large-sized (> 2,000 microns 2) cells in the DRG
      after axotomy. There was a 165% increase in the number of labeled cells after
      sciatic transection and a 260% increase after spinal nerve transection which
      results in axotomy of all the cells in the ganglion. The further increase after
      spinal nerve transection suggests that the induction occurred in axotomized
      neurons. PPT mRNA label was also present in a reduced number of small (< 1,000
      microns 2) cells after axotomy. SP immunoreactivity was also induced in medium-
      and large-sized cells and reduced in small-sized cells. Our findings suggest that
      the expression of the PPT gene and SP is differentially regulated in different
      subpopulations of DRG neurons after axotomy and is consistent with the hypothesis
      that tachykinins may be important in both sensory transmission and regeneration.

PMID- 7518008
TI  - Involvement of protein kinase C in cAMP regulation of myelin basic protein gene
      expression.
AB  - Since synthesis of myelin components has been seen to be stimulated by cAMP in
      both oligodendrocytes and Schwann cells we have begun investigating the specific
      sequence(s) in the 5' flanking region of the myelin basic protein (MBP) gene that
      are responsible for the induction of MBP transcription by cAMP. Using stably
      transfected cell lines containing various deletions of the MBP promoter directing
      the bacterial chloramphenicol acetyltransferase (CAT) gene we have identified a
      region of the MBP gene that is inhibitory to stimulation by increased cAMP
      levels. This inhibition can be overcome by pretreating the cells with 12-O
      tetradecanoylphorbol 13-acetate (TPA) for 48 hr. The effects on MBP gene
      expression modulated by TPA and cAMP involve altered DNA-protein interactions in
      the 5' end of the MBP promoter. The effect of TPA also appears to be mediated by
      down-regulation of protein kinase C.

PMID- 7518009
TI  - Retinal ganglion cell survival in vitro maintained by a chondroitin sulfate
      proteoglycan from the superior colliculus carrying the HNK-1 epitope.
AB  - We recently reported evidence implicating a superior colliculus-derived
      chondroitin sulfate proteoglycan (SCCP) in the trophic support of cultured
      retinal ganglion cells (Schulz et al., 1990). In the present work we show
      preparations of the SCCP to be reactive with an antibody (CS-56) to chondroitin
      sulfate types A and C and with the HNK-1 antibody. Reaction with the HNK-1
      antibody allowed us partially to purify the native proteoglycan by immunoaffinity
      chromatography. HNK-1 reactive material was further processed by a combination of
      molecular sieve chromatography in the presence of 4M guanidine HCL followed by
      anion exchange chromatography to yield a product that migrated
      electrophoretically as a single band in polyacrylamide gel with an apparent
      molecular weight of not less than 400 k. The SCCP, when added to a fully defined
      culture medium, maintained the survival of the vast majority (80%) of the
      ganglion cells over a 16 hr culture period with 86% of these cells showing a
      profusion of processes; few ganglion cells (10%) survived in the absence of the
      proteoglycan. Electrophoretic analysis of nonreduced preparations of the molecule
      did not reveal any low molecular weight silver stained components that may have
      remained associated with the molecule after guanidine HCL treatment. However, two
      bands corresponding to molecular weights of around 60 and 80 k were reproducibly
      observed on polyacrylamide gels following electrophoresis of the molecule in the
      presence of beta-mercaptoethanol. Our findings provide further evidence
      suggesting a role for a chondroitin sulfate proteoglycan carrying the HNK-1
      epitope in the trophic support of central neurones.

PMID- 7518010
TI  - Myelin basic protein content of aggregating rat brain cell cultures treated with
      cytokines and/or demyelinating antibody: effects of macrophage enrichment.
AB  - The demyelinative potential of the cytokines interleukin-1 alpha (IL-1 alpha),
      interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) has
      been investigated in myelinating aggregate brain cell cultures. Treatment of
      myelinated cultures with these cytokines resulted in a reduction in myelin basic
      protein (MBP) content. This effect was additively increased by anti
      myelin/oligodendrocyte glycoprotein (alpha-MOG) in the presence of complement.
      Qualitative immunocytochemistry demonstrated that peritoneal macrophages, added
      to the fetal telencephalon cell suspensions at the start of the culture period,
      successfully integrated into aggregate cultures. Supplementing the macrophage
      component of the cultures in this fashion resulted in increased accumulation of
      MBP. The effect of IFN-gamma on MBP content of cultures was not affected by the
      presence of macrophages in increased numbers.

PMID- 7518011
TI  - The pentafraction of hydroxyethyl starch inhibits ischemia-induced compartment
      syndrome.
AB  - Pentafraction (PF), a solution of biodegradable hydroxyethyl starch
      macromolecules with molecular weights of 10 to 100 x 10(4) daltons, has been
      shown to minimize tissue edema by sealing interendothelial clefts at the
      capillary level. The effect of PF on ischemia-reperfusion-induced compartment
      syndrome was studied. Ten rabbits underwent bilateral femoral artery occlusion
      following ligation of branches from the terminal aorta to the popliteal artery.
      After 7 hours of ischemia, reperfusion was established with heparinized
      polyethylene shunts. Experimental animals (n = 5) received PF and control animals
      (n = 5) received normal saline (NS) as an intravenous infusion (30 mL/kg) for 1
      hour, beginning 10 minutes after shunt placement. During reperfusion, anterior
      compartment pressure was continuously monitored in the left lower extremity. To
      quantitate oxidative metabolism, triphenyltetrazolium chloride (TTC) reduction
      (micrograms of TTC per milligram of protein) of tibialis anterior muscle from the
      right lower extremity was measured at femoral artery occlusion, 7 hours of
      ischemia, and 2 hours of reperfusion. In the NS group, anterior compartment
      pressure significantly increased from the end of the ischemic interval, 10.8 +/-
      4.14 to 36.4 +/- 9.9 mmHg and 44.6 +/- 15.4 mmHg, after 1 and 2 hours of
      reperfusion (p < 0.007) compared with the PF group, which did not change
      significantly, 10.6 +/- 2.6 to 11.4 +/- 12.9 mmHg and 7.4 +/- 2.8 mmHg, after 1
      and 2 hours of reperfusion (p < 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518013
TI  - [Clinical features and diagnosis of paroxysmal nocturnal hemoglobinuria:
      correlates with the deficiency of GPI-anchored membrane proteins].
AB  - Glycosyl phosphatidylinositol (GPI)-anchored membrane proteins are deficient in
      the blood cells affected by paroxysmal nocturnal hemoglobinuria (PNH). The
      relation of the deficiencies of CD59 and CD14 with the clinical features of PNH
      are reported. CD59 binds to complement components C8 and C9 derived from human
      sera and inhibits the C5b-9-mediated hemolysis in a species-selective manner. The
      CD59-binding sites were revealed to be localized in the alpha subunit of C8 and
      in the "b" domain of C9 (thrombin fragment). The deficiency of CD59 in PNH is
      causatively related to the hemolytic features in PNH. A monocyte differentiation
      antigen, CD14, is deficient in the affected PNH monocytes. CD14 is reported to be
      one of the receptors to lipopolysaccharide (LPS). LPS-binding to the monocytes
      were revealed to be mediated through CD14 on monocytes. Enhancement of LPS
      binding to monocytes by the presence of serum was not seen to PNH-affected
      monocytes. PNH-affected monocytes showed impaired TNF-alpha production in
      response to LPS. The deficiency of CD14 indicates the abnormality in PNH-affected
      monocytes, however, its significance in the clinical features of PNH is to be
      clarified.

PMID- 7518014
TI  - [Peripheral blood stem cell transplantation: present status and future
      prospects].
AB  - This is a comprehensive review of autologous peripheral blood stem cell
      transplantation (PBSCT). Collection of peripheral blood stem cells (PBSC) does
      not require anesthesia and is less invasive compared to harvesting marrow cells.
      As the hematopoietic recovery speed after autologous PBSCT is fast, the procedure
      is associated with less complication compared to marrow transplantation. Thus,
      high-dose therapy can safely be administered, without the use of aseptic
      measures, in a larger number of hospitals. Preliminary therapeutic results for
      the treatment of relapsed childhood acute lymphoblastic leukemia appears to be
      equivalent to that obtained by application of allogeneic bone marrow
      transplantation. Alternate use of PBSC includes routine application after
      consolidation therapy as one of growth factors. Use of PBSC in allogeneic setting
      has been under intense investigation. Collection, processing and storage of PBSC
      will shortly become a part of routine procedure in major blood centers and banks.

PMID- 7518015
TI  - Sensitivity of intestinal alkaline phosphatase to L-homoarginine and its
      regulation by subunit-subunit interaction.
AB  - The inhibitory effect of levamisole and L-homoarginine on alkaline phosphatases
      (ALP, orthophosphoric monoester phosphohydrolase, EC. 3.1.3.1) in various tissues
      was studied to characterize differences in the mechanism of inhibition of ALP
      isoenzymes. The ALP activity from the placenta, kidneys, and a clonal osteogenic
      cell line, MC3T3-E1, was hyperbolically inhibited with a dependency on the
      concentration of levamisole (Ki0.5 = 10-12 microM) or L-homoarginine (Ki0.5 = 1
      mM), but the activity of intestinal ALP was little inhibited by 240 microM
      levamisole and sigmoidally inhibited by L-homoarginine (Ki0.5 = 13 mM). Hill plot
      analysis of the L-homoarginine inhibition data showed that the Hill coefficient
      values of the placenta, kidney, and osteogenic cells were around 0.9-1.0 and that
      of the intestine was 1.8. The effect of sodium dodecyl sulfate (SDS), which may
      decrease the subunit-subunit interaction, on the L-homoarginine inhibition of the
      intestinal ALP was tested. The L-homoarginine concentration-dependent inhibition
      curve changed from sigmoidal to hyperbolic, and the Hill coefficients decreased
      with increasing concentrations of SDS. These results suggest that the differences
      in inhibition by L-homoarginine and affinity changes of intestinal ALP for L
      homoarginine are caused by the subunit-subunit interaction of oligomers.

PMID- 7518012
TI  - From the Centers for Disease Control and Prevention. Progress toward global
      eradication of poliomyelitis, 1988-1993.

PMID- 7518016
TI  - Development of a monoclonal antibody-based competitive inhibition enzyme-linked
      immunosorbent assay for detection of Bacillus piliformis isolate-specific
      antibodies in laboratory animals.
AB  - A competitive inhibition enzyme-linked immunosorbent assay (ELISA) was developed
      to detect Bacillus piliformis isolate-specific antibodies in serum specimens from
      rats and gerbils experimentally infected with B. piliformis isolates R1, R2, or
      M. Detection was based on the ability of serum antibodies to block binding of B.
      piliformis isolate-specific monoclonal antibodies to purified B. piliformis
      flagella. Application of this assay to serum specimens collected from sham
      infected or experimentally infected rats and gerbils demonstrated that the serum
      specimens were capable of specifically inhibiting the binding of B. piliformis
      isolate-specific monoclonal antibodies to homologous flagella preparations (> 70%
      inhibition) only when the serum specimens were from animals infected with the
      homologous B. piliformis isolate. Only one false-negative and false-positive
      result were obtained when 80 serum specimens were tested by this competitive
      inhibition ELISA. In addition, we demonstrated that little nonspecific inhibition
      of monoclonal antibody binding occurred (< 30% inhibition) in this immunoassay
      specific inhibition of monoclonal antibody binding by serum was due to serum
      antibody and a serum's ability to inhibit binding of monoclonal antibodies to
      purified B. piliformis flagella was correlated with antibody reactivity with B.
      piliformis flagella but not with serum antibody reactivity to whole B. piliformis
      organisms. These results suggest that this monoclonal antibody-based competitive
      inhibition assay could be successfully applied to the serologic identification of
      isolates involved in naturally occurring B. piliformis infections in laboratory
      animals.

PMID- 7518017
TI  - Interleukin 1 and tumor necrosis factor production as the initial stimulants of
      liver ischemia and reperfusion injury.
AB  - The mechanisms by which polymorphonuclear neutrophils (PMNs) are recruited by the
      ischemic and reperfused liver are still unknown. The purpose of this study was to
      determine whether tumor necrosis factor-alpha (TNF) and/or interleukin-1 alpha
      (IL-1) acted as potential mediators for PMN infiltration after liver ischemia and
      reperfusion. The potential effect of FK 506, a powerful immunosuppressant, was
      also studied. Male Sprague-Dawley rats were subjected to 60 and 90 min of total
      hepatic ischemia, with an extracorporeal porto-systemic shunt. FK 506 (0.3 mg/kg)
      was intravenously administered 4 hr before ischemia (FK 506 group), and control
      animals received normal saline solution (NS group). Plasma TNF, IL-1 levels, and
      PMN infiltration in liver tissue were serially examined at the end of ischemia,
      5, 30, 60, and 360 min after reperfusion. The degree of liver necrosis was
      assessed at 360 min following reperfusion. In the NS group, IL-1 and TNF revealed
      a transient elevation at 30 and 60 min after reperfusion, following 60 min of
      ischemia. When the ischemia was increased to 90 min, the IL-1 activity had a
      rapid elevation (330.5 +/- 129 pg/ml) at 5 min, which remained at high levels
      (197.8 +/- 70.4 pg/ml) until 6 hr after reperfusion, whereas the TNF activity
      decreased to normal levels following a similar peak (355 +/- 181.9 pg/ml) at 5
      min after reperfusion. The time course of IL-1 release in the NS group, with 90
      min of ischemia, correlated directly with the PMN infiltration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7518018
TI  - Primary thymic carcinoma: a clinicopathological and immunohistochemical study.
AB  - During the treatment of five cases of thymic carcinoma, we conducted a
      clinicopathological and immunohistochemical study. The patients included four
      males and one female, whose ages ranged from 50 to 69 years. The histologic
      breakdown was squamous cell carcinoma in four and small cell carcinoma in one.
      Immunohistochemically, the squamous cell carcinomas were positive for cytokeratin
      (intermediate molecular weight) and keratin. However, staining was negative for
      Leu-7 and chromogranin. A complete resection was achieved in only one case. In
      all four of the remaining cases, the resection was incomplete due to invasion
      into adjacent organs and disseminated lesions. Thymic carcinoma is a tumor for
      which a higher response rate can be expected from multidisciplinary therapy than
      that for lung cancer. Therefore, it is desirable, from the clinical view, to
      determine clinical staging and to establish standard operative procedures
      comprising mediastinal lymph node dissection as well as effective chemotherapy.
      With respect to pathology, it is hoped that an improved histologic classification
      will be developed.

PMID- 7518019
TI  - Malignant germ cell tumors in childhood.
AB  - The outlook for patients with germ cell tumors was poor before the advent of
      effective chemotherapy. In this study the outcome of multiagent chemotherapy in
      children treated for germ cell tumor is assessed. Between January 1984 and
      December 1990, 107 patients were diagnosed to have germ cell tumors. Postsurgical
      therapy was based on tumor site, stage, and histology. Combination chemotherapy
      was employed in patients with Stages I and II disease with postoperative raised
      tumor markers and all patients with Stages III and IV. Between 1984-1988,
      patients received cisplatin, vinblastin, bleomycin, and methotrexate (PVB-M), and
      thereafter between 1988-1990, they received bleomycin, etoposide, and cisplatin
      (BEP). Of 34 patients treated with PVB-M and 27 treated with BEP, the complete
      remission rate was 40% and 85%, respectively, and the overall survival was 30% at
      5 years for PVB-M and 80% at 3 years for BEP. We conclude that etoposide with
      cisplatin is superior to vinblastin with cisplatin in the treatment of advanced
      germ cell tumors because of greater efficacy, decreased toxicity, and better
      compliance in children.

PMID- 7518020
TI  - Induction chemotherapy in the treatment of patients with carcinoma of the
      esophagus.
AB  - A prospective randomized phase III trial was carried out at Songklanagarind
      Hospital from August 1988 to December 1990. The objectives of the study were to
      evaluate the effect of chemotherapy regimen in squamous cell carcinoma of the
      esophagus and to determine whether induction chemotherapy improves symptom-free
      period and survival in these patients compared to surgical treatment alone.
      Twenty-four patients were randomized to receive 2 cycles of chemotherapy, cis
      platinum 100 mg/m2 intravenously on day 1, bleomycin 10 mg/m2 loading dose on day
      3, followed by 10 mg/m2/day continuous intravenous infusion on days 4 through 7,
      and vinblastine 3 mg/m2 given intravenously on days 1, 8, 15, 22. The cycle was
      repeated on day 29. Fifteen patients completed 2 courses of chemotherapy and
      among these, 2 patients had a complete clinical response (13%), 6 (40%) had a
      partial response, and 7 patients (47%) had no response. Four patients died during
      chemotherapy treatment. Grade 3 hematologic toxicity (ECOG criteria) was observed
      in 47% (7/15) of patients. Twenty-two patients were randomized to conventional
      treatment (surgery alone). Median survival time was 17 months in both groups.
      However, early survival appeared to be better in the control group. Kaplan-Meier
      survivals at 6 months were 69% and 89% and at 3 years were 31% and 36% for the
      induction chemotherapy group and control group, respectively. The survival time
      differences were not statistically significant (P = 0.186). These findings
      demonstrate that although this chemotherapy regimen had some effect on squamous
      cell carcinoma of esophagus, it did not improve survival. On the contrary,
      survival seems to be better in the control group. The 6-month survival
      discrepancy between both groups might be due to the poor nutritional status of
      our patients, who may better tolerate smaller dosages of chemotherapy.

PMID- 7518021
TI  - Loss of alpha 1 beta 1 and reduced expression of other beta 1 integrins and CAM
      in lung adenocarcinoma compared with pneumocytes.
AB  - Alterations in expression of various cell-adhesion molecules have been reported
      in a variety of malignant tissues. However, little is known about how lung
      adenocarcinomas differ in CAM expression from the normal lung. We analyzed the
      expression of integrins alpha 1 beta 1 through alpha 6 beta 1, intercellular
      adhesion molecule (ICAM)-1, neural cell adhesion molecule (NCAM), and lymphocyte
      function antigen (LFA)-3, CD44, and the two carbohydrate antigens, Lewisx (Le(x))
      and sialosyl-Le-Le(x) of lung adenocarcinoma cells, and compared them with
      autologous pneumocytes. CAM expression was studied by an immunohistochemical
      method using monoclonal antibodies, and computerized image analysis was used to
      quantify the immunoperoxidase-staining intensity. The normal lung alveolar cells
      strongly expressed the integrins alpha 1 beta 1 and alpha 3 beta 1, and fairly
      expressed alpha 2 beta 1, alpha 4 beta 1, alpha 5 beta 1, and alpha 6 beta 1.
      ICAM-1, LFA-3, and CD44 were strongly expressed, whereas NCAM, the Le(x) and
      sialosyl-Le-Le(x) antigens, were expressed weakly. In contrast, we did not detect
      expression of the alpha 1 beta 1 integrin on any autologous lung adenocarcinoma
      cells, and they showed on average a 50% reduction in labeling relative intensity
      units for the integrin common chain marker beta 1, the specific integrins alpha 3
      beta 1, alpha 5 beta 1, and alpha 6 beta 1, and ICAM-1, and LFA-3. Examination of
      the adjacent small blood vessel endothelium in malignant lung tissues did not
      reveal any major alterations in CAM expression, the small vessel endothelium of
      the normal and malignant lung tissues appeared with a similar CAM profile. These
      results suggest that lung adenocarcioma cells have a lack of alpha 1 beta 1
      expression and significant reduction in some other integrin beta 1 and CAM
      expression in comparison with their autologous pneumocytes. This aberration in
      CAM expression by the lung adenocarcinoma cells may be involved in their loss of
      proliferation control and may interfere with leukocyte adhesion to tumor cells,
      enabling the tumor to escape immunodestruction.

PMID- 7518023
TI  - [Early diagnosis of prostatic cancer: state of the art].

PMID- 7518022
TI  - Aprotinin improves myocardial recovery after ischemia and reperfusion. Effects of
      the drug on isolated rat hearts.
AB  - The effects of aprotinin, a protease inhibitor, on the ischemic and nonischemic
      isolated rat heart was investigated with the use of the modified Langendorff
      model. During phase I of the study, hearts were perfused with either low-dose
      aprotinin (10(5) KIU/L), high-dose aprotinin (10(6) KIU/L), or normal saline
      solution added to modified Krebs-Henseleit solution. No statistically significant
      differences in contraction amplitude, contractility, coronary flow, and wet/dry
      heart weight ratio were observed among the three groups of hearts. In phase II,
      hearts were exposed to a 40-minute period of global ischemia at 31 degrees C.
      Ischemic arrest was induced by warm cardioplegia. Before ischemia and during
      cardioplegia, hearts were perfused with either aprotinin 10(6) KIU/L (n = 10) or
      normal saline solution (n = 10) for 30 minutes. On reperfusion, recovery of
      hearts treated with aprotinin was significantly better than that of control
      hearts, as reflected by better contractility (analysis of variance, p = 0.011),
      higher coronary flow (p < 0.025), and lower creatine kinase levels (p < 0.05). No
      statistically significant differences in contraction amplitude were observed
      between the two groups. When the effect of ischemia within each group of hearts
      was analyzed, the preserving effect of aprotinin was even more pronounced. In the
      control group, ischemia caused a decrease in contractility (p < 0.025) and a
      decrease in oxygen consumption (p = 0.006); by contrast, in the aprotinin group
      the preischemic values were maintained. Accordingly, we conclude that aprotinin
      at concentrations up to 10(6) KIU/L has no deleterious effect on normally
      perfused hearts and has a significant protective effect on the ischemic heart
      when used in high doses in the preischemic period.

PMID- 7518024
TI  - [The paradox of G-CSF].

PMID- 7518025
TI  - Role of selectins in development of adult respiratory distress syndrome.
AB  - The acute lung injury of adult respiratory distress syndrome (ARDS) is
      characterised by inflammatory cell accumulation and activation in the lung.
      Selectins are a family of adhesion molecules implicated in leucocyte-endothelial
      adhesion, whose receptors can exist in a cleaved, soluble form. We investigated
      whether circulating soluble selectin adhesion molecules, obtained from ARDS at
      risk patients, were associated with subsequent ARDS development. 82 patients, at
      risk of ARDS, were enrolled from three well-defined groups (multiple trauma,
      pancreatitis, perforated bowel). Plasma samples were obtained on hospital
      presentation and soluble L, E, and P, selectins were quantified with a sandwich
      enzyme-linked immunosorbent assay (ELISA). 14 patients subsequently developed
      ARDS. Initial plasma soluble L-selectin (sL-selectin) levels were significantly
      lower in patients who progressed to ARDS compared to those who did not (p =
      0.0001; 95% Cl for mean in ARDS patients as percent of that in non-ARDS patients,
      27-61%). Moreover concentrations were lower than in 62 normal volunteers (range
      0.37-6.55, median 1.83 micrograms/mL, n = 62), suggesting that a selective
      reduction of sL-selectin correlates with susceptibility. In addition, a
      significant correlation was found between low values of sL-selectin and indices
      of subsequent lung injury including requirement for ventilation (p = 0.0001) and
      degree of respiratory failure (p = 0.0001). A significant correlation was also
      found between low values of sL-selectin and patient mortality (p = 0.002). These
      results elucidate the inflammatory cell endothelial interactions in the early
      stages of ARDS and may be of prognostic value.

PMID- 7518026
TI  - [Hospices--palliative care throughout the world].

PMID- 7518027
TI  - Early childhood intervention: the law.

PMID- 7518030
TI  - Localization of tyrosine hydroxylase mRNA in the axons of the hypothalamo
      neurohypophysial system.
AB  - With in situ hybridization we examined the localization of mRNA coding for
      tyrosine hydroxylase (TH) in the rat hypothalamo-neurohypophysial system (HNS)
      under conditions of acute osmotic stress. Fifteen min after salt loading,
      hybridization signal of TH mRNA could be located in the magnocellular
      hypothalamic nuclei and in the median eminence (ME). In untreated animals, TH
      mRNA was detected only in the ME. In osmotically challenged animals that had been
      pretreated with colchicine, signals for TH mRNA remained confined to the ME,
      while pretreatment of salt loaded rats with a polymerase II transcription
      inhibitor resulted in labelling of the magnocellular perikarya but a decrease of
      the hybridization signal in the ME. Our results suggest that also TH mRNA is
      among the RNAs which are axonally transported in the HNS. TH mRNA can probably be
      stored in axons of the hypothalamo-neurohypophysial tract, to be transported
      retrogradely and translated upon certain stimuli.

PMID- 7518028
TI  - Nitric oxide synthase gene expression in cholinergic neurons in the rat brain
      examined by combined immunocytochemistry and in situ hybridization
      histochemistry.
AB  - The expression of mRNA for the calmodulin-dependent form of brain nitric oxide
      synthase (NOS) was examined in cholinergic cells of the rat brain using a method
      combining in situ hybridization histochemistry with immunocytochemistry for
      choline acetyltransferase (ChAT) in the same brain sections. We constructed a
      riboprobe specific for brain NOS by subcloning a 493 bp fragment of the coding
      region which displayed low homology to other forms of NOS. The general
      distribution of NOS mRNA was in excellent agreement with previous studies using
      the full-length probe or NADPH diaphorase histochemistry. NOS mRNA was observed
      in many brain structures and relative levels were quantitated using grain
      counting procedures in a number of cholinergic and non-cholinergic neuronal
      groups throughout the brain. In the forebrain, ChAT-immunoreactive cells or cell
      groups were observed in medial septum (MS), vertical limbs of diagonal band (DBV)
      and horizontal limbs of diagonal band (DBH), nucleus basalis magnocellularis
      (NBM), substantia innominata (SI), and striatum (ST). In the brainstem, the
      cholinergic groups studied included those located in the pedunculopontine
      tegmental nucleus (PPTN), the laterodorsal tegmental nucleus (LDTN), the nucleus
      parabigeminalis and several motor nuclei. For NOS mRNA quantitation, silver
      grains overlying ChAT-stained neuronal profiles in sections on emulsion-dipped
      slides were counted digitally. In the LDTN and PPTN, virtually all the ChAT
      positive cells expressed NOS mRNA at high levels. In MS, DBV and SI, about 30-50%
      of the ChAT-positive cells expressed NOS mRNA at low-to-moderate levels. Less
      than 20% of ChAT-positive neurons in the other cholinergic populations studied
      expressed NOS mRNA; the NBM was one of these low-expressing populations. Many
      scattered non-cholinergic cells expressing NOS mRNA were found in the striatum
      and cerebral cortex. In other non-cholinergic regions, high NOS mRNA expression
      was observed in the islands of Calleja, thalamic and hypothalamic nuclei, several
      amygdaloid nuclei, regions related to the optic tract, the interpeduncular
      nucleus, and the supramammillary nucleus. The heterogeneous distribution of NOS
      mRNA implies complex roles for nitric oxide neurotransmission in brain function,
      including for the cholinergic phenotype. Additionally, given the postulated
      involvement of nitric oxide in neurodegeneration, the widely varying levels of
      expression of NOS within identified central cholinergic neurons may relate to
      differential vulnerability of this phenotype in disease or aging.

PMID- 7518031
TI  - Processing, axonal transport and cardioregulatory functions of peptides derived
      from two related prohormones generated by alternative splicing of a single gene
      in identified neurons VD1 and RPD2 of Lymnaea.
AB  - The VD1/RPD2 mRNA precursor in identified neurons VD1 and RPD2 of the freshwater
      snail Lymnaea stagnalis is alternatively spliced to yield two related variants
      encoding two distinct yet related preprohormones, named the VD1/RPD2-A and -B
      preprohormones. Here, we report the isolation and structural characterization of
      alpha 1, alpha 2 and beta peptides from dissected neurons VD1 and RPD2. The alpha
      1 and alpha 2 peptides are derived from VD1/RPD2-A and B prohormones,
      respectively, whereas beta peptide is identical for both prohormones. In
      addition, we report the isolation and structural characterization of the alpha 2
      peptide from the heart, demonstrating that the mature peptides are transported
      and released in the heart. The pharmacological actions of synthetic alpha 1 and
      alpha 2 peptides on isolated auricle preparations of the Lymnaea heart were
      examined. The two alpha peptides have similar excitatory effects on beat rate and
      beat amplitude, while their potencies differed considerably, indicating that
      alternative splicing results in structurally and functionally overlapping,
      through non-identical, sets of peptides.

PMID- 7518029
TI  - Differential influence of haloperidol and sulpiride on dopamine receptors and
      peptide mRNA levels in the rat striatum and pituitary.
AB  - We examined the effect of chronic administration (14 days) of haloperidol (2
      mg/kg/day) or sulpiride (100 mg/kg/day), on the mRNA levels of various genes in
      the rat striatum and pituitary by quantitative in situ and Northern blot
      hybridizations. In the pituitary, haloperidol and sulpiride induced similar
      increases of mRNAs of pro-opiomelanocortin (POMC) (+65% and +73%), prolactin
      (PRL) (+821% and +840%) and growth hormone (GH) (+32% and +47%), but sulpiride
      induced a greater increase of D2R mRNA (+125%) than haloperidol (+92%). In the
      striatum, sulpiride and haloperidol had different effects: sulpiride induced a
      higher increase than haloperidol of both preproenkephalin A (PPA) mRNA (+67%
      versus +47%) and D2 dopamine receptor (D2R) mRNAs (+72% versus +40%). Moreover,
      haloperidol and sulpiride had opposite effects on substance P (SP) mRNA.
      Haloperidol decreased the amount of SP mRNA by 20% while sulpiride increased it
      by 20%. The D1 dopamine receptor (D1R) mRNA level was not significantly modified
      after either treatment. Our results demonstrate that the effect of a chronic
      haloperidol treatment on striatal dopamine receptors and neuropeptide mRNA levels
      is different to that of sulpiride, whereas it is similar on pituitary hormones
      mRNA levels.

PMID- 7518033
TI  - The expression of neuropeptides and their mRNAs in the trigeminal mesencephalic
      nucleus following masseteric nerve transection.
AB  - By in situ hybridization and immunohistochemistry, we examined the expression of
      neuropeptides such as neuropeptide Y (NPY), galanin (Gal), substance P (SP),
      vasoactive intestinal polypeptide (VIP) and their mRNAs in the rat mesencephalic
      trigeminal nucleus (Mes5) following masseteric nerve transection. On the side
      contralateral to the nerve transection, none of the peptides examined were
      labeled in Mes5 cell bodies. However, on the side ipsilateral to the lesion, NPY,
      Gal and preprotachykinin (PPT) mRNAs appeared in Mes5 cell bodies. Double
      labeling for mRNAs by in situ hybridization and retrograde tracer fluoro-gold
      (FG) revealed that almost all (96-97%) the FG-labeled neurons which were cut
      expressed NPY and Gal mRNAs, whereas less neurons (87%) expressed PPT mRNA. NPY
      and Gal-like immunoreactivities were detected in Mes5 cell bodies ipsilateral to
      the axotomy. The results suggested that these neuropeptides play roles in
      adaptive processes after peripheral nerve injury in Mes5 neurons as they are
      thought to do so in dorsal root ganglion neurons.

PMID- 7518032
TI  - Molecular analysis of expression in rat brain of NSP-A, a novel neuroendocrine
      specific protein of the endoplasmic reticulum.
AB  - Previous studies have established that the novel neuroendocrine-specific NSP gene
      encodes three carboxy-terminally overlapping proteins, NSP-A, NSP-B and NSP-C
      which are anchored to membranes of the endoplasmic reticulum. Here, we report
      results of studies in which expression of NSP-A in rat brain was investigated.
      Immunization of mice with a bacterial hybrid protein containing almost all NSP-A
      sequences led to the isolation of five monoclonal anti-NSP-A antibodies. The
      corresponding epitopes were found to be mapping to two regions unique to NSP-A.
      In Western blot analysis of rat cerebrum and cerebellum using these antibodies,
      proteins of about 145 kDa were detected. An immunohistochemical study of rat
      brain revealed the presence of NSP-A in many brain regions, particularly in
      cerebellar Purkinje cells, in neurons of the superior colliculus and of the
      pyriform and enthorhinal cortex, in fibers of the basal ganglia and several
      hippocampal regions including CA3 (stratum lucidum) and the dentate gyrus, in the
      induseum griseum and in the subcommissural organ, suggesting a role of NSP-A in
      many areas of the brain.

PMID- 7518034
TI  - [The level of the eosinophils in the blood, serum immunoglobulins and circulating
      immune complexes and interferon production in patients with unilocular
      echinococcosis depending on the location of the cysts].
AB  - The correlations between blood eosinophils, serum immunoglobulins (Ig),
      circulating immune complexes (CIC) content, alpha- and gamma-interferon (IFN)
      production and HLA class I antigens were analyzed in 33 patients with hydatid
      disease aged 37.5 +/- 1.5 years. Direct correlation between the activity of gamma
      IFN production, blood eosinophils, IgG and specific IgE content was found in
      patients with multiple pulmonary damage. In this group the high level of CIC
      correlated with the high content of IgG and specific IgE. In patients with
      solitary and multiple cysts in the liver in spite of high alpha- and gamma-IFN
      production the levels of total and specific IgE were low, IgG and CIC contents
      were moderate and eosinophils percent was low. In patients with combined damage
      of the liver and multiple cysts in the abdominal cavity high CIC production
      correlated directly with high total IgE content. In the total group of patients
      percent of HLA B5 carriers was significantly higher than in controls: 36.6 and
      14.7 respectively (R = 0.01 after Fischer) that correlated with comparatively
      active gamma-IFN production in patients with the pulmonary and the liver cysts.
      The possible explanation of the different immune response in patients with the
      different localisation of the parasite cysts are discussed.

PMID- 7518035
TI  - An analysis of sequence variation in the beta chain framework and complementarity
      determining regions of an allo-reactive T cell receptor.
AB  - Current models of T cell receptor (TCR) structure are generally based on the
      homology observed between the TCR and the immunoglobulins. Furthermore, these
      models have predicted the locations of framework and complementarity determining
      regions within the alpha- and beta-chain variable regions. In order to test the
      validity of these models, we have generated a series of mutations within the V
      beta domain of an allo-reactive TCR and determined their effect on antigen
      recognition.

PMID- 7518036
TI  - Construction of a specific DNA probe for diagnosis of melioidosis and use as an
      epidemiological marker of Pseudomonas pseudomallei.
AB  - Pseudomonas pseudomallei is a causative agent of melioidosis. The disease
      manifestations range from fulminant sepsis to asymptomatic seroconversion. In
      septicemic cases, a mortality rate of 80-90% is reported. Rapid and specific
      diagnosis has become important to the clinical microbiology laboratory. We have
      developed a P. pseudomallei-specific DNA probe. The cloned fragment, herein
      designated pKKU-S23L, contained 1.5 kb of P. pseudomallei chromosomal DNA. A
      radioactively labelled pKKU-S23L insert could detect 1.5 ng of its genomic DNA or
      40,000 P. pseudomallei cells. The probe was highly specific for P. pseudomallei
      DNA and did not cross-hybridize with DNAs prepared from other related bacteria.
      Using pKKU-S23L as a probe in total cellular DNA digestions and Southern blot
      hybridization, we were able to classify 60 P. pseudomallei clinical isolates
      obtained from individual melioidosis patients into eight categories. Therefore,
      this probe has a potential not only for use in development of specific detection
      of bacterial DNA in clinical specimens but also for application in
      epidemiological studies of P. pseudomallei.

PMID- 7518039
TI  - Effect of transfection of human poly(ADP-ribose)polymerase in Chinese hamster
      cells on mutagen resistance.
AB  - Poly(ADP-ribose)polymerase (PARP) is a DNA-binding protein that is activated upon
      induction of DNA breaks and supposed to play a role in DNA repair. To elucidate
      the effect of overexpression of PARP on the resistance of cells to mutagens,
      Chinese hamster ovary cells (both the line CHO-9 and the mutagen-hypersensitive
      derivative 27-1) were transfected with the human PARP cDNA along with pSV2neo.
      Treatment of the transfected cell population with a high dose of MNNG and
      selection with G418 gave rise to a significant increase of neo+ clones, as
      compared to the control transfection with pSV2neo + salmon sperm DNA. The
      frequency of survivors in these mass culture experiments was lower, however, than
      after transfection with the bacterial ada gene encoding the DNA repair protein O6
      alkylguanine-DNA alkyltransferase. Thus transfection of PARP cDNA in CHO cells is
      only weakly effective in inducing alkylation resistance. This was confirmed by
      analyzing the mutagen resistance of individual PARP transfectant clones derived
      from CHO-9 and 27-1 cells that expressed increased levels of PARP mRNA, protein
      and PARP activity. These strains were slightly more resistant to the toxic effect
      of MMS and showed a reduced frequency of MMS-induced chromosomal aberrations. CHO
      9-PARP transfectants also gained resistance to UV. From these data we conclude
      that, in CHO cells, PARP is limiting in handling critical lesions during the
      repair process and that increase of the amount of PARP protein can elicit some
      protection against genotoxic effects of mutagens.

PMID- 7518037
TI  - Characterization of contaminating DNA in Taq polymerase which occurs during
      amplification with a primer set for Legionella 5S ribosomal RNA.
AB  - An amplification product that occurred in negative controls of a PCR using a
      primer system for Legionella 55 ribosomal RNA was characterized by direct
      sequencing. The amplification product did not hybridize to a Legionella specific
      oligonucleotide. It was derived from bacterial DNA contaminating Taq DNA
      polymerase, a phenomenon that was previously reported for amplification reactions
      with universal primer sets for bacterial 16S rRNA. The sequence of the 5S
      ribosomal fragment had close homology to the 5S-rRNA of the species Pseudomonas
      fluorescens, Pseudomonas aeruginosa, Alcaligenes faecalis, and Azotobacter
      vinelandii. These findings confirm that the DNA contaminations in Taq DNA
      polymerase belong to other species than Thermus aquaticus or Escherichia coli.

PMID- 7518038
TI  - Mutation spectrum of 4-nitroquinoline 1-oxide-damaged single-stranded shuttle
      vector DNA transfected into monkey cells.
AB  - 4-Nitroquinoline 1-oxide (4NQO) is a potent mutagen and carcinogen which induces
      two main guanine adducts at positions C8 and N2. We recently determined the
      mutation spectrum induced by the ultimate metabolite of 4NQO, acetoxy-4
      aminoquinolone 1-oxide in the M13lacZ'/E. coli lacZ delta M15 alpha
      complementation assay. Our data suggested that dGuo-C8-AQO induces (per se or via
      AP sites) G to Pyr transversions. Here we report our study on 4NQO mutagenesis in
      monkey cells. 4NQO lesions were induced in vitro on a single-stranded (ss) DNA
      shuttle vector carrying the supF tRNA gene. This vector was able to replicate
      both in mammalian cells and in bacteria. The mutations induced in monkey cells
      were screened by the white/blue beta-galactosidase activity assay in E. coli. We
      took advantage of the peculiar feature of ss supF DNA in which the extent of
      secondary structure may be a function of the temperature, with the dependence of
      the 4NQO-specific adduct spectrum on DNA secondary structure. We reasoned that
      mutational spectra derived from damage induced in the presence (20 degrees C) or
      absence (70 degrees C) of DNA secondary structure should be different. The result
      of sequencing a total of 89 induced and spontaneous mutants confirmed that the
      spectra are statistically different. These data suggest that the two 4NQO guanine
      adducts may induce different mutations.

PMID- 7518040
TI  - Mutagenicity of K-region oxides and imines of chrysene, benzo[c]phenanthrene and
      benzo[g]chrysene in Salmonella typhimurium.
AB  - The K-region oxides and imines of chrysene, benzo[c]phenanthrene and
      benzo[g]chrysene were investigated for mutagenicity in Salmonella typhimurium
      TA98 and TA100, using two different exposure media. All six compounds were
      mutagenic under all four experimental conditions. The imines were 17-3800 times
      more potent than the corresponding oxides. Omission of KCl (125 mM) from the
      exposure medium resulted in enhanced mutagenic effects. The enhancement was
      stronger in strain TA98 (3.1-5.2-fold) than in strain TA100 (1.3-2.5-fold),
      suggesting an influence on the bacteria rather than on the chemicals.

PMID- 7518042
TI  - Modulation of the spontaneous G2 phase blockage in Fanconi anemia cells by
      caffeine: differences from cells arrested by X-irradiation.
AB  - The effect of caffeine on the endogenous G2 phase cell cycle blockage of Fanconi
      anemia (FA) cells was compared with the effect of caffeine on the G2 phase
      blockage induced in control cells by X-irradiation. The G2 phase accumulations in
      FA cells could be completely resolved by exposure to 1.5 mM caffeine. This was
      also observed in three brothers with endogenous G2 phase blockage due to unusual
      BrdU sensitivity. In contrast, G2 phase blockage induced by X-irradiation was
      only partially resolved by exposure to caffeine. The rescued G2 phase cells from
      FA patients were arrested within the following G1 phase compartments. This was
      not seen in X-irradiated cells from control donors. These results point towards a
      different nature and/or repair mechanism of the endogenous G2 phase lesion in FA
      cells compared to that induced by X-irradiation in control cells.

PMID- 7518041
TI  - Co-mutagenic effect of tannic acid on ring-X chromosome loss induced by mitomycin
      C in sperm cells of Drosophila melanogaster.
AB  - To investigate the effects of tannic acid (TA) on ring-X chromosome loss,
      Drosophila melanogaster females exposed to different TA concentrations were
      crossed with untreated, methyl methanesulfonate (MMS)- or mitomycin C (MMC)
      treated males which carried a ring-X chromosome. Progeny were analyzed for loss
      of the ring-X. The results of this in vivo study showed that TA had no
      suppressing effect on chromosome loss occurring spontaneously or after induction
      by MMS in mature spermatozoa. In contrast, TA caused a significant increase in
      the frequency of MMC-induced ring-X loss. The increase caused by this co
      mutagenic effect reached values of 34, 33 and 40% at TA concentrations of 10, 25
      and 50 mM, respectively. These increments may reflect the action of TA on a
      uvrABC-type enzyme which, by increasing the double-strand breaks (DSBs), somehow
      interferes with the post-replicational repair responsible for the final DSB
      correction.

PMID- 7518043
TI  - Oxidative mutagens induce intrachromosomal recombination in yeast.
AB  - Active oxygen species are thought to be involved in the causation of a number of
      diseases including cancers. We have investigated the effect of 5 oxidative
      mutagens, methyl viologen (paraquat), mitomycin C, phenylhydrazine, cumene
      hydroperoxide and hydrogen peroxide, on the frequency of both intrachromosomal
      recombination and interchromosomal recombination in the yeast Saccharomyces
      cerevisiae. All of the chemicals significantly increased the frequency of
      intrachromosomal recombination in a dose-dependent manner. Only hydrogen peroxide
      increased the frequency of interchromosomal recombination at the doses tested in
      this study. A role for hydroxyl radical (.OH) in the effect of H2O2 on
      recombination is indicated by the ability of the radical scavenger dimethyl
      sulfoxide (DMSO) to significantly inhibit the induction of both intrachromosomal
      and interchromosomal recombination by H2O2. The results presented here give
      further support for the suitability of intrachromosomal recombination
      measurements as a short-term test for the detection of mutagens and carcinogens.

PMID- 7518044
TI  - Clonal rearrangements in human irradiated fibroblasts.
AB  - The cytogenetic dose response following in vivo localized irradiation is
      difficult to establish because of the occurrence of clones defined by chromosome
      alterations, with various proliferative rates. The biological meaning of these
      clones is not well understood. Two sets of experiments were performed to follow
      their behavior. R-banded karyotypes were established on human fibroblasts
      irradiated either before or after initiation of the cultures. Clones were
      observed in cultures developed after irradiation of biopsies, whereas irradiated
      cultures exhibited karyotypes with multiple non-clonal rearrangements. This
      difference suggests that most radiation-induced chromosome anomalies do not
      confer a selective advantage on the carrier cells in vitro. The appearance of
      clonal anomalies following biopsy irradiation would rather be a consequence of a
      strong selection at the time of the growth of the cells out of the explants,
      which would give rise to the progeny of a limited number of progenitor cells.

PMID- 7518045
TI  - The inhibitory effects of coffee on radical-mediated oxidation and mutagenicity.
AB  - Hydrogen peroxide (H2O2) has been implicated as a major contributor to coffee
      mutagenicity and genotoxicity in vitro. We have used three assays to show the
      gradual formation of H2O2 in freshly prepared roasted ground coffee and in
      instant coffees over time reaching levels of 400-450 microM after a 1-h
      incubation period. Formation of H2O2 occurs through an auto-oxidation process
      where polyphenolics, in the presence of transition metals, reduce atmospheric
      oxygen. However, because of these polyphenolics, coffee also possesses in vitro
      antioxidant activity as shown by its capacity to inhibit lipid peroxidation in
      Fenton-catalysed hydroxylation reactions. The pro- and antioxidative effects of
      coffee are also reflected in its mutagenic and antimutagenic activity in the Ames
      test. Coffee is directly mutagenic in strains TA100 and TA102 due to H2O2
      formation. However, coffee is also an antioxidant and antimutagen. This beverage
      exerts a strong protective effect against the mutagenicity and cytotoxicity
      induced by the oxidant t-butylhydroperoxide (t-BOOH). Thus, coffee, like many
      antioxidants, exhibits dual effects in vitro which are highly dependent upon
      parameters such as dose, atmospheric oxygen, transition metals as well as the
      biological and chemical endpoints used for measurement. Consequently, the data
      obtained on the pro- and antioxidant properties of foods and beverages from in
      vitro bioassays must be interpreted with caution and the results are not easily
      extrapolated in vivo to assess the impact on human health.

PMID- 7518047
TI  - Two-dimensional DNA electrophoresis in mutation detection.
AB  - Accurate detection of gene mutations is important in many areas of biology and
      medicine. In fundamental studies of mutagenesis it is often necessary to assess
      all possible mutations, either spontaneous or induced by genotoxic agents, in a
      particular gene or gene sequence to explain a given cellular or physiological
      endpoint. In molecular medicine comprehensive detection of all possible mutations
      in a disease gene is required before clinical genetic testing becomes feasible.
      Of the many mutation detection methods currently available none is capable of
      scanning for all possible mutations in a cost-effective manner. Here we show that
      by two-dimensional DNA electrophoretic separation, on the basis of both size and
      base pair sequence, in principle all mutations in a given gene can be detected.
      This is illustrated by some data on 2-D electrophoresis of 10 exons of the cystic
      fibrosis gene.

PMID- 7518046
TI  - Mechanisms of the in vitro antimutagenic action of chlorophyllin against
      benzo[a]pyrene: studies of enzyme inhibition, molecular complex formation and
      degradation of the ultimate carcinogen.
AB  - Mechanisms of the antimutagenic action of chlorophyllin (CHL) towards
      benzo[a]pyrene (BP) were studied in vitro. In the Salmonella assay, CHL inhibited
      the mutagenic activity of BP in the presence of an S9 activation system and was
      particularly effective against the direct-acting ultimate carcinogen,
      benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). Spectral studies indicated
      that the time-dependent hydrolysis of BPDE to tetrols was augmented in the
      presence of CHL concentrations on the order of 5 microM. Dose-related inhibition
      of several cytochrome P450-dependent enzyme activities was observed upon addition
      of CHL to in vitro incubations. Spectral changes for the interaction between CHL
      and cytochrome P450 indicated that CHL does not bind to the active site of the
      enzyme, but exerts its inhibitory effect indirectly. This was achieved by
      inhibiting NADPH-cytochrome P450 reductase (Ki approximately 120 microM with
      cytochrome c as substrate), and did not involve lowering of the effective
      substrate concentration by complex formation with the procarcinogen. It is
      concluded that the in vitro antimutagenic activity of CHL towards BP involves
      accelerated degradation of the ultimate carcinogen, with inhibition of carcinogen
      activation occurring only at high CHL concentrations. The latter mechanism is
      unlikely to occur in vivo following p.o. administration due to the limited uptake
      of CHL from the gut, but tissue concentrations may be sufficiently high to cause
      degradation of BPDE.

PMID- 7518050
TI  - DNA strand breakage, cytotoxicity and mutagenicity of hydrogen peroxide treatment
      at 4 degrees C and 37 degrees C in L5178Y sublines.
AB  - Cells from the L5178Y murine lymphoma subline LY-R are twofold more resistant to
      killing by ionizing radiation than the subline LY-S. In contrast, LY-R cells are
      more sensitive to killing by hydrogen peroxide. Cells of the two sublines in
      logarithmic growth phase were treated with hydrogen peroxide in phosphate
      buffered saline for 1 h at 4 degrees C or 37 degrees C. From the comparison of
      D(o) values it followed that at 37 degrees C LY-R were 3.6 times more sensitive
      to the killing effect of H2O2 than LY-S cells; at 4 degrees C they were 11 times
      more sensitive. Treatment with hydrogen peroxide at 4 degrees C gave a
      considerable sparing effect, which was substantially greater for the LY-S
      subline; for LY-S cells D(o) was 5.7 times lower at 37 degrees C than at 4
      degrees C, for LY-R cells only 1.9 times. The mutation frequency (HGPRT) in LY-R
      cells was increased in proportion to H2O2 concentration and was the same at both
      treatment temperatures. In contrast, mutation frequencies initially increased,
      then decreased with increasing H2O2 concentration in LY-S cells treated at 4 or
      37 degrees C. The concentration at which the decline was initiated was higher at
      4 than at 37 degrees C. DNA damage after H2O2 treatment (both temperatures, 5
      min) was estimated from the 'comet' assay (single-cell gel electrophoresis). The
      initial damage, but not the residual damage, differed significantly in LY
      sublines. A period of slower repair (between 3 and 10 min) was found in LY-R
      cells.

PMID- 7518051
TI  - Regulatory requirement for three dose levels and proof of tissue localisation in
      rodent genetic toxicity assays--a call for supporting data.

PMID- 7518049
TI  - Determination of hprt mutant frequencies in T-lymphocytes from a healthy
      pediatric population: statistical comparison between newborn, children and adult
      mutant frequencies, cloning efficiency and age.
AB  - Somatic cell mutant frequencies at the hprt locus of the X-chromosome were
      measured with the T-lymphocyte cloning assay in a healthy pediatric population.
      Assays were performed on 49 subjects (29 males and 20 females) ranging in age
      from 0.08 to 15.2 years. A statistical analysis of the thioguanine-resistant
      (TGr) mutant frequency (MF), unselected cloning efficiency (CE) and age was
      performed using data obtained in this study and those previously obtained in our
      laboratory on 66 newborn umbilical cord blood samples and 230 adult blood
      samples. For statistical comparisons pediatric subjects were divided into 4
      groups. Group I included cord blood samples (age 0 years); Group II were subjects
      between 0 and 5 years; Group III were between 6 and 11 years and Group IV were
      between 12 and 17 years. The ln MF of Groups I and II were significantly lower
      than Groups III and IV (p < 0.05). The mean ln MF for each of Groups I-IV was
      significantly lower than the adult value. The cloning efficiency for Group I was
      significantly lower than that for Groups II-IV and adults. The relationships
      among the ln MF, unselected CE and age were expressed by the equations: ln (MF) =
      0.945 -2.453 CE (p < 0.001) and ln (MF) = 0.114 + 0.063 age (p 0.004). The slope
      coefficients for unselected CE and age were significantly different from adults
      (p < 0.05). Regression analysis of combined data from Groups I-IV and adults were
      performed using both age and unselected CE as well as terms to reflect
      differences in their relationships with ln MF in adults and children. The results
      showed that the intercept and the age coefficients differ significantly for
      children and adults after adjustment for CE and yielded the following equations:
      ln (MF) = 0.548 -1.676 CE + 0.075 age, (Groups I-IV) and ln (MF) = 2.263 -1.676
      CE + 0.014 age (adults). An alternative statistical model using ln (age ), ln
      (MF) = 0.381 -1.767 CE + 0.673 ln (age + 1), (p < 0.001), describes the rapid
      increase in MF with age that levels off in late adolescence. These findings
      demonstrate the changing influence of age on mutant frequency in the pediatric
      population as compared to the adult populations. These studies also illustrate
      that the increase in background somatic mutant frequencies at the hprt locus in T
      lymphocytes is not linear from birth to adolescence and is significantly
      different from that seen in the adult population.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7518052
TI  - Mycoflora of post-harvest maize and wheat grains and the implication of their
      contamination by molds.
AB  - Thirteen fungi including toxigenic Aspergillus nidulans and A. clavatus were
      isolated from the grains. The isolated fungi grew well at 25-30 degrees C. A.
      clavatus and A. nidulans were grown in liquid maize yeast extract medium and
      wheat yeast extract medium. Both fungi produced amylases on the two media and on
      the basal medium at 30 degrees C. During incubation more total reducing sugars
      were detected in maize grains than in wheat while non-reducing sugars were
      detected than reducing sugars in both grains. A. clavatus showed highest amylase
      activities at 25-30 degrees C and at a pH 7-8 while 30 degrees C and pH 6.0 were
      the optimum conditions for highest amylase activities of A. nidulans. During
      incubation with both fungi a decrease in the protein and carbohydrate contents of
      both grains was recorded while more fat was accumulated in the grains.

PMID- 7518048
TI  - The effects of antioxidants and enzymes involved in glutathione metabolism on
      mutagenesis by glutathione and L-cysteine.
AB  - The effects of small molecular weight antioxidants and antioxidant enzymes on the
      mutagenicities of glutathione (GSH) and L-cysteine were studied in Salmonella
      typhimurium strain TA102. GSH and cysteine mutagenesis were inhibited by
      antioxidants and radical scavengers such as alpha-tocopherol, Trolox C, butylated
      hydroxyanisole (BHA), and retinyl acetate. Superoxide dismutase (SOD) had no
      effect, but catalase and horseradish peroxidase (HRP) inhibited mutagenesis. The
      heat-denatured enzymes had no effect on mutagenesis. Cysteine mutagenesis was
      enhanced by native and by heat-denatured rat-kidney post-mitochondrial
      supernatant, and by ferric ions. H2O2 and the H2O2-generating system of glucose
      glucose oxidase (GOX) were mutagenic in TA102. Synergistic increases in
      mutagenesis were obtained in systems containing combinations of GSH or cysteine,
      with either H2O2 or the H2O2-generating system of glucose-GOX. GSH peroxidase
      (GPX) had no effect on mutagenesis of GSH or of H2O2, whereas the synergistic
      increase in mutagenesis by a combination of GSH and H2O2 was effectively
      inhibited by GPX. The results suggest strongly that, at least in biochemically
      defined systems, GSH and cysteine mutagenesis are oxidative in nature, and
      involve reactive forms of oxygen and/or other radicals.

PMID- 7518053
TI  - Modulation of neurotransmission in guinea-pig airways by galanin and the effect
      of a new antagonist galantide.
AB  - Galanin is localised to sensory nerve fibres and cholinergic nerves in airways.
      Galantide has been shown to be a novel high affinity antagonist to galanin, since
      it inhibits galanin-mediated inhibition of glucose-induced insulin secretion and
      the neuronal action of galanin in the brain. We investigated the effects of
      galanin on cholinergic and non-adrenergic, non-cholinergic (NANC) responses to
      electrical field stimulation in guinea-pig airways, and examined whether
      galantide antagonised the effect of galanin on neurotransmission. Galanin (10(
      6)M) had no effect on cholinergic bronchoconstrictor responses and inhibitory
      NANC relaxation responses in trachea, but significantly inhibited excitatory NANC
      bronchoconstrictor responses in bronchi which is due to the release of
      tachykinins. Galantide (10(-8)-10(-6)M) had no effect on the galanin-induced
      inhibition of the excitatory NANC responses. Galanin may be important in the
      modulation of excitatory NANC responses but not cholinergic and inhibitory NANC
      responses in guinea-pig airways. This modulatory effect may be via a different
      type of galanin receptor than is present in other organs.

PMID- 7518054
TI  - Effects of sequential removal of rats from a group cage, and of individual
      housing of rats, on substance P, cholecystokinin and somatostatin levels in the
      periaqueductal grey and limbic regions.
AB  - The effect of specific stressful stimuli on neuropeptide levels was studied in
      rat brain regions known to be involved in the mediation of stress responses and
      anxiety. Rats were sequentially removed, one by one with 20-min intervals from
      group cages and immediately decapitated. A selective increase of the somatostatin
      level was observed in the amygdala in the rats taken for sacrifice second last
      and last, compared to the rats taken earlier from the respective group cage
      (increases by 40 to 69%, p < 0.05 or p < 0.01). Isolation of rats in single cages
      for 24 h or 1 week before sacrifice, increased the substance P level in the
      dorsal periaqueductal grey by 26 and 27% (p < 0.05 in both cases), respectively,
      compared to group housed rats. In group housed rats treated with diazepam (5
      mg/kg, s.c.) 140 min before sacrifice, the level of substance P in the rostral
      hippocampus and dorsal periaqueductal grey was reduced by 40% (p < 0.001) and 28%
      (p < 0.05), respectively, compared to saline treated controls. In conclusion,
      handling, as well as a single dose of the anxiolytic drug diazepam, appears to
      induce rapid, selective and region-specific changes of regional brain peptide
      levels in the rat. The effects of handling are likely to be related to the acute
      stress response and are probably not secondary to increased plasma glucocorticoid
      levels.

PMID- 7518055
TI  - [AIDS and palliative cures].

PMID- 7518056
TI  - [Sudeck's atrophy. 3 clinical cases].
AB  - Three patients fulfilling criteria for Sudeck's atrophy (reflex sympathetic
      dystrophy syndrome--RSDS) are described and etiological, pathogenetic and
      clinical features of the disease are reviewed. RSDS is associated with a wide
      variety of precipitating factors, each of whom, often in concomitance with
      metabolic diseases and psychiatric disturbances, may cause the same clinical
      syndrome, which continues in a "vicious circle" of feed-back mechanisms,
      correlated with sympathetic hyperactivity. The symptoms may begin gradually and
      the disorder progresses in stages lasting from weeks to months. The management
      has not yet been established. Generally, the earlier the syndrome is recognized,
      the better the results of treatment will be. Analgesics, salmon calcitonin and
      physiokinesitherapy are recommended. Psychological support is advisable. In more
      severe patients sympathetic blockade and surgical sympathectomy may be necessary.
      The effects of hyperbaric oxygen treatment must still be assessed.

PMID- 7518057
TI  - Reciprocal connections of lateral septal neurons and neurons in the lateral
      hypothalamus in the rat: a combined phaseolus vulgaris-leucoagglutinin and Fluoro
      Gold immunocytochemical study.
AB  - Reciprocal connections between lateral septal neurons and neurons in the lateral
      hypothalamus/lateral preoptic area were studied in the rat. The anterograde
      tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde tracer
      Fluoro-Gold (FG) were simultaneously injected into the lateral septum. After
      double-immunocytochemistry, PHA-L-labeled terminals were found in synaptic
      contact with dendrites of retrogradely FG-labeled neurons in the lateral
      hypothalamic/lateral preoptic area.

PMID- 7518058
TI  - Block of nicotinic acetylcholine-activated channels of cultured mouse myotubes by
      isoflurane.
AB  - It is well known that volatile anesthetics cause muscle relaxation. A block of
      nicotinic acetylcholine-activated receptors (nAChRs) in staedy state by
      isoflurane was recently reported. Pulses of acetylcholine (ACh) were applied to
      outside-out patches from mouse myotubes using a system for ultra-fast solution
      exchange allowing the study of the block of nAChRs by isoflurane under conditions
      similar to the situation during synaptic transmission. Isoflurane in
      concentrations used during general anesthesia blocked approximately 50% of the
      receptors within 0.5 ms after application. The block of nAChRs could be partially
      relieved by application of high concentrations of ACh. Therefore, muscle
      relaxation and the reduction of the amplitude of postsynaptic currents by
      isoflurane may be caused by the block of nAChRs reported here.

PMID- 7518059
TI  - Protein-synthesis inhibitor blocks (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole
      4-propionic acid (AMPA)-or substance P-induced phase shift of the circadian
      rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro.
AB  - The mammalian suprachiasmatic nucleus (SCN) has been identified as a circadian
      pacemaker. N-methyl-D-aspartate (NMDA), non-NMDA and substance P receptors have
      been suggested to be involved in handling of photic information in the SCN. In
      the Aplysia eyes, in which the circadian clocks are involved, serotonin- or cAMP
      induced phase changes of the circadian rhythm were reported to be blocked by
      protein-synthesis inhibitors. Therefore, we investigated whether protein
      synthesis inhibitor can block the non- NMDA receptor agonist (R,S)-alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA)- or substance P
      (SP)-induced phase changes of SCN activity rhythm. Although application of 10
      microM cycloheximide alone during the early part of the subjective night did not
      cause phase change, it blocked both 10 microM AMPA- and 1 microM SP-induced phase
      delay. The present result suggests that protein synthesis may be required in the
      manifestation of AMPA- and SP-induced phase change of circadian clock.

PMID- 7518061
TI  - Tachykinin induced regulation of excitatory amino acid responses in the rat
      spinal cord in vitro.
AB  - The interaction between neurokinin and excitatory amino acid receptors in the
      spinal cord have been characterised using the neonatal rat spinal cord in vitro
      preparation. Ventral root (VR) depolarization evoked by N-methyl-D-aspartate
      (NMDA) and quisqualate was reversibly enhanced in the presence of subthreshold
      concentrations of neurokinin A (NKA; 1.0-10 nM), but not by substance P (1.0-5.0
      nM). When substance P (SP) was replaced by the metabolically stable substance P
      methyl ester (SPOMe), both NMDA and quisqualate responses were significantly
      enhanced. VR depolarization evoked by kainate was not altered by any of the
      neurokinin (NK) receptor agonists. In the presence of the endopeptidase
      inhibitors, bestatin, captopril and thiorphan (each 1.0 microM), SP significantly
      enhanced NMDA-evoked responses. The selective NK1 receptor antagonist (+/-) CP96
      345 (100 nM) reversibly blocked the enhancement of NMDA-evoked depolarization by
      SPOMe. Furthermore, MEN10 376 (50 nM), a selective NK2 receptor antagonist
      blocked the enhancement of NMDA- and quisqualate-evoked depolarization by NKA.
      The protein kinase C and protein kinase A inhibitor staurosporine (1.0 microM)
      blocked the enhancement of excitatory amino acid-induced responses by NK-receptor
      activation. However, whilst NKA-evoked ventral root depolarization was completely
      abolished in the presence of staurosporine, SPOMe- and SP-induced depolarizations
      were unaffected. These data show that activation of NK1 or NK2 receptors enhances
      NMDA- and quisqualate-evoked ventral root depolarization in the neonatal rat
      spinal cord. The interaction between neurokinin and excitatory amino acid
      receptors involves protein kinase C activation.

PMID- 7518060
TI  - Multiple mitogenic signalling pathways in chromaffin cells: a model for cell
      cycle regulation in the nervous system.
AB  - Adult rat chromaffin cells proliferate in vivo in response to neurally derived
      signals. Their proliferation in vitro is stimulated either by peptide growth
      factors or by activators of adenylate cyclase or protein kinase C that mimic the
      effects of neurotransmitters in adrenal medullary nerve endings. Differing
      susceptibilities to inhibitors and potentiators suggest that growth factors,
      cyclic AMP-dependent protein kinases and protein kinase C act via partially
      distinct and partially overlapping signalling pathways. Depolarization inhibits
      the mitogenic response to NGF, through a mechanism that apparently involves
      activation of voltage-gated calcium channels, while sparing the response to
      phorbol esters that activate PKC. Activators of adenylate cyclase also inhibit
      the response to NGF. The findings suggest that during normal development,
      neurally derived signals supersede growth factors in regulating proliferation of
      chromaffin cells by selectively inhibiting or co-opting portions of growth factor
      signalling pathways. This model might be generally applicable to the development
      of the nervous system.

PMID- 7518062
TI  - Further evidence that pyrroloquinoline quinone interacts with the N-methyl-D
      aspartate receptor redox site in rat cortical neurons in vitro.
AB  - In this study, we show that the essential nutrient pyrroloquinoline quinone (PQQ;
      50 microM) regulates N-methyl-D-aspartate (NMDA; 10 microM) receptor activity
      primarily by reversing the increase in the frequency of openings of the receptor
      associated ion channel after chemical reduction with dithiothreitol (DTT; 1 mM).
      Similar to other redox-active agents, PQQ (50-200 microM) had no effect on the
      single-channel conductance or arithmetic mean open time of NMDA-activated events.
      In other experiments, we observed that inhibitory effects of PQQ (50 microM) on
      NMDA (30 microM)-induced whole-cell responses could be abolished by prior N
      ethylmaleimide (500 microM) alkylation of the putative thiol residues that likely
      comprise the redox site of the receptor. These results demonstrate that PQQ
      modulates the NMDA receptor by directly oxidizing its redox modulatory site.

PMID- 7518063
TI  - The consequence of delayed versus immediate nerve repair on the properties of
      regenerating sensory nerve fibres in the adult rat.
AB  - Transected saphenous neurones were allowed to regenerate for 3 months via distal
      stumps of sural nerve following an immediate or a 3 month delayed repair. The
      number of DRG neurons surviving following the 3 months regeneration period were
      approximately 60% of normal after both immediate and delayed repair. The
      percentage of DRG cell bodies identified by the application of Fluro-gold
      proximal to the repair site and immunopositive for SP, CGRP and galanin was
      increased following both early and delayed repair compared to baseline values.
      These values were not significantly different for early repair compared to late
      repair. Similarly, peripheral measurements of SP in the proximal stump of
      saphenous nerve (by radioimmunoassay) were not significantly different between
      models with primary repair compared to delayed repair. These results suggest that
      the intrinsic regeneration properties of primary sensory neurones are not
      impaired when repair is delayed.

PMID- 7518064
TI  - Nitric oxide synthase in the CNS of the Atlantic salmon.
AB  - This study describes for the first time the presence and distribution of the
      nitric oxide (NO) synthesizing enzyme, NO synthase (NOS), in the retina of a
      teleost. NADPH diaphorase (NADPHd) histochemistry and NOS immunohistochemistry
      revealed both NOS immunoreactive and NADPHd positive structures in photoreceptor
      outer segments, amacrine cells, horizontal cells and ganglion cells. Since NO is
      known to stimulate the synthesis of cGMP, our results implicate an important role
      for NO in retinal function, especially in cGMP related events in the
      photoreceptors.

PMID- 7518067
TI  - Cerebellar nitric oxide synthase, cGMP and motor function in two lines of
      cerebellar mutant mice, Staggerer and Wriggle Mouse Sagami.
AB  - We investigated the hypothesis that nitric oxide (NO) is involved in the
      cerebellar motor function, by measuring nitric oxide synthase (NOS) activities
      and cGMP in the cerebellum using two lines of mutant mice having motor
      dysfunction, Staggerer (SG) and Wriggle Mouse Sagami (WMS). In SG, the NOS
      activity per cerebellum was reduced to 5.8% of that of the controls, while no
      significant change was observed in WMS. The cerebellar cGMP in SG was reduced to
      3.3% of that of the controls and to 43% in WMS. In contrast with these
      neurochemical markers of NO, the locomotor dysfunction and the number of falls
      were greater in WMS than in SG. The reductions of the neurochemical markers of NO
      are consistent with the results of the previous neuropathological studies in SG
      and WMS whereas the cerebellar motor dysfunction was independent of these
      neurochemical and neuropathological changes.

PMID- 7518068
TI  - Stimulation of protein-tyrosine phosphorylation in gerbil hippocampus after
      global forebrain ischemia.
AB  - Tyrosine phosphorylation in the gerbil hippocampus after a transient ischemia was
      analyzed by immunoblotting and immunohistochemistry. In control hippocampus, the
      phosphotyrosine was detected in many proteins of 165 to 10 kDa and the
      immunostain showed a distinct distribution. The ischemic insult induced various
      alterations of the phosphotyrosine immunoreactivities in both ischemia-resistant
      and -vulnerable neurons which were associated with alterations in the expression
      of 165 to 19 kDa-immunoreactive bands. These results suggest that tyrosine
      phosphorylation is involved in the ischemic hippocampus to play a role in the
      development of early and delayed neuronal deaths in CA4 and CA1 neurons,
      respectively.

PMID- 7518065
TI  - Early regeneration in vitro of adult mouse sciatic axons is dependent on local
      protein synthesis but may not involve neurotrophins.
AB  - The sensory axons of the adult mouse sciatic nerve were shown to regenerate after
      a local test crush lesion in vitro in a serum-free medium. The average outgrowth
      distance of the leading axons after culturing for 3 days was 2.8 +/- 0.1 mm,
      which was shorter than in vivo (3.8 +/- 0.2 mm). With the use of a
      compartmentalised culture system we could show that regeneration was partially
      dependent on local protein synthesis in the injury region. The initial stages of
      regeneration did not seem to involve neurotrophins since both K252a and K252b,
      selective and nontoxic inhibitors of the neurotrophin actions, failed to inhibit
      axonal growth. The present in vitro model system offers favourable conditions to
      investigate the early events of the regeneration process in an adult mammalian
      peripheral nerve.

PMID- 7518069
TI  - Dermatome mapping in the rat hindlimb by electrical stimulation of the spinal
      nerves.
AB  - In rats treated with Evans blue (i.v.), electrical stimulation of the lumbar
      spinal nerves produced an extravasation zone in the skin. Stimulation of L1
      produced extravasation in the lower abdomen; that of L2, in the cranial region of
      the hindlimb; that of L3, in the ventral region of the hindlimb and the medial
      paw; that of L4, in the lateral region of the hindlimb and the middle paw; that
      of L5, in the caudal region of the hindlimb and the lateral paw; and that of L6,
      in the caudal region of the hindlimb and the scrotum. Since the substance P
      antagonist FK224 inhibited the extravasation caused by stimulation of the sciatic
      nerve, the extravasation zones appeared to be related to antidromic activation of
      afferent C-fibers. Thus, a dermatome of afferent C-fibers was revealed in rats.

PMID- 7518066
TI  - Interaction between substance P and excitatory amino acid receptors in modulation
      of nociceptive responses of cat spinal dorsal horn neurons.
AB  - Co-effects of microelectrophoretic application of 2-amino-5-phosphonovalerate
      (APV), ketamine, 6,7-dinitroqinoxaline-2,3-dione (DNQX), kynurenate (Kyn) and
      spantide on 34 spinal dorsal horn neurons were studied. Co-application of
      spantide and APV or DNQX produced a synergetic inhibition of responses by tibial
      stimulation in 10/23 and 3/8 neurons, respectively, and also in 3/8 neurons by
      administration of DL-sodium homocysteate. Spantide enhanced APV- or ketamine
      induced inhibition of C responses of 8/19 neurons to sural stimulation, DNQX
      induced that of 2/4 neurons to gastrocnemius-soleous stimulation (GS), and Kyn
      induced that to both sural (8/19) and GS (2/4). The results suggest an
      interaction of SP and NMDA, non-NMDA receptors in processing spinal nociception.

PMID- 7518070
TI  - Peripheral odontogenic keratocyst.
AB  - The gingival cyst of the adult exhibits an epithelial lining that is essentially
      the same as the lateral periodontal cyst. Although the gingival cyst of the adult
      exhibits some morphologic variability, its lining is generally considered to be
      nonkeratinized. Nonetheless, rare cases of gingival cyst of the adult that
      exhibit a keratinized epithelial lining have been reported in the literature.
      There is now a growing tendency to consider this variant as a separate entity.
      This article describes six cases of gingival cysts that exhibit the histologic
      features of the odontogenic keratocyst. Evidence from this series suggests that
      the biologic behavior of this subset of gingival cysts is different from that of
      the generic gingival cyst of the adult and that the term peripheral odontogenic
      keratocyst more accurately describes this entity.

PMID- 7518071
TI  - Rare case of keratin-producing multiple gingival cysts.
AB  - A rare case of multiple keratin-containing gingival cysts is presented. It is
      suggested that either a common dental lamina stem cell with diverging
      differentiation pathways or another cell of origin may be responsible for the
      formation of these unique cysts.

PMID- 7518072
TI  - [Measurements of amylase isoenzymes in sera and saliva of patients after
      radiotherapy because of larynx carcinoma].
AB  - Serum and salivary alpha-amylase were measured for controls and patients with
      laryngeal carcinoma before, and after localised irradiation including salivary
      glands. Additionally amylase isoenzymes in sera were measured using mini-column
      method. A significant increase in amylasemia was observed after irradiation.
      Alpha-amylase activity in saliva was decreased after irradiation but differences
      were not statistically significant due to the significant decrease of protein in
      saliva of irradiated group. An increase of salivary isoenzyme S activity was
      observed while pancreatic isoenzyme activity was not altered. This method allows
      easy differentiation of hyperamylasemia due to irradiation of parotid gland and
      disorders of the pancreas. Alpha-amylase activity measurements may detect
      metabolic changes in salivary glands after irradiation.

PMID- 7518073
TI  - [Immunocytochemistry in the differential diagnosis of the head and neck tumors].
AB  - Immunocytochemical analysis in fine-needle aspirates were performer in 46 cases
      of head and neck tumors. Immunocytochemical studies helped to establish the
      differential diagnosis of all diagnostically difficult cases. The application of
      3 monoclonal antibodies against keratin, vimentin and LCA permitted to
      differentiate basic types of malignant tumors.

PMID- 7518074
TI  - Distribution of intraepithelial nerve fibers in the feline glottis.
AB  - It is well known that the protective laryngeal closure is elicited by mechanical
      or chemical stimulation of the epithelium in the glottis. In this study we used
      light microscopic observation and relative examination of the intraepithelial
      nerve fibers in the glottis to clarify the perceptive mechanism using
      immunohistochemical methods. In the anterior glottis, a moderate number of
      protein gene product 9.5-immunoreactive intraepithelial nerve fibers were
      observed, most of which were found to be located just anterior to the vocal
      process. The number of fibers in the upper surface of the vocal fold was larger
      than that in the free edge and the lower surface. Only a few calcitonin gene
      related polypeptide-immunoreactive fibers were seen, and substance P
      immunoreactive fibers were rarely seen. On the other hand, a dense distribution
      of protein gene product 9.5-immunoreactive nerve fibers was observed throughout
      the epithelium of the posterior glottis. The number of calcitonin gene-related
      peptide-immunoreactive fibers was about 20% that of protein gene product 9.5
      immunoreactive fibers, whereas the number of substance P-immunoreactive fibers
      was only 1% to 2%. The results of this study suggest that possible existence of
      regional differences in the perceptive mechanism between the anterior and
      posterior glottis.

PMID- 7518076
TI  - An intervening sequence (IVS) in the 16S rRNA gene of the eubacterium
      Helicobacter canis.
AB  - PCR amplicons enlarged by approximately 250bp were generated from the 16S rRNA
      (rrs) genes of certain strains of the recently described Helicobacter species, H.
      canis. The DNA sequence of the rrs gene of one such strain was determined, and it
      was shown that an intervening sequence (IVS) of 235bp followed nucleotide 199 in
      the rrs sequence. In four other H. canis strains, identical or similar IVSs were
      found, always at the same location in the rrs gene. The secondary structures of
      the RNA transcripts of the IVSs were predicted. They were characterised by the
      presence of a conserved stem-loop structure, a potential recognition site for RNA
      processing enzymes. Ribosomal RNA was compared from a strain of H. canis with and
      without the IVS-containing rrs gene. In the former 16S rRNA appeared as two
      fragments, whose sizes were consistent with cleavage at either side of the IVS,
      and which were not subsequently religated. The IVS sequence was not represented
      elsewhere in the H. canis genome. Its evolutionary significance is discussed.

PMID- 7518077
TI  - Recognition of oxidized abasic sites by repair endonucleases.
AB  - The recognition of 'regular' and 'oxidized' sites of base loss (AP sites) in DNA
      by various AP endonucleases was compared. Model substrates with regular AP sites
      (resulting from mere hydrolysis of the glycosylic bond) were produced by damaging
      bacteriophage PM2 DNA by exposure to low pH; those with AP sites oxidized at the
      C-4'- and C-1'-position of the sugar moiety by exposure to Fe(III)-bleomycin in
      the presence of H2O2 and to Cu(II)-phenanthroline in the presence of H2O2 and
      ethanol, respectively. The results confirmed that AP sites-together with single
      strand breaks-are indeed the predominant type of DNA modification in all three
      cases. For the recognition of 4'-oxidized AP sites, a 400-fold higher
      concentration of Escherichia coli exonuclease III and between 5-fold and 50-fold
      higher concentrations of bacteriophage T4 endonuclease V, E. coli endonuclease
      III and E. coli FPG protein were required than for the recognition of regular AP
      sites. In contrast, the recognition of 4'-oxidized AP sites by E. coli
      endonuclease IV was effected by 4-fold lower concentrations than needed for
      regular AP sites. 1'-oxidized AP sites (generated by activated Cu(II)
      phenanthroline) were recognized by endonuclease IV and exonuclease III only
      slightly (3-fold and 13-fold, respectively) less efficiently than regular AP
      sites. In contrast, there was virtually no recognition of 1'-oxidized AP sites by
      the enzymes which cleave at the 3' side of AP sites (T4 endonuclease V,
      endonuclease III and FPG protein). The described differences were exploited for
      the analysis of the DNA damage induced by hydroxyl radicals, generated by
      ionizing radiation or Fe(III)-nitrilotriacetate in the presence of H2O2. The
      results indicate that both regular and 1'-oxidized AP sites represent only minor
      fractions of the AP sites induced by hydroxyl radicals.

PMID- 7518078
TI  - The heterodimeric subunit SRP9/14 of the signal recognition particle functions as
      permuted single polypeptide chain.
AB  - The targeting of nascent polypeptide chains to the endoplasmic reticulum is
      mediated by a cytoplasmic ribonucleoprotein, the signal recognition particle
      (SRP). The 9 kD (SRP9) and the 14 kD (SRP14) subunits of SRP are required to
      confer elongation arrest activity to the particle. SRP9 and SRP14 form a
      heterodimer which specifically binds to SRP RNA. We have constructed cDNAs that
      encode single polypeptide chains comprising SRP9 and SRP14 sequences in the two
      possible permutations linked by a 17 amino acid peptide. We found that both
      fusion proteins specifically bound to SRP RNA as monomeric molecules folded into
      a heterodimer-like structure. Our results corroborate the previous hypothesis
      that the authentic heterodimer binds to SRP RNA in equimolar ratio. In addition,
      both fusion proteins conferred elongation arrest activity to SRP(-9/14), which
      lacks this function, and one fusion protein could functionally replace the
      heterodimer in the translocation assay. Thus, the normal N-and C-termini of both
      proteins have no essential role in folding, RNA-binding and in mediating the
      biological activities. The possibility to express the heterodimeric complex as a
      single polypeptide chain facilitates the analysis of its functions and its
      structure in vivo and in vitro.

PMID- 7518079
TI  - A novel RNA-binding motif in omnipotent suppressors of translation termination,
      ribosomal proteins and a ribosome modification enzyme?
AB  - Using computer methods for database search, multiple alignment, protein sequence
      motif analysis and secondary structure prediction, a putative new RNA-binding
      motif was identified. The novel motif is conserved in yeast omnipotent
      translation termination suppressor SUP1, the related DOM34 protein and its
      pseudogene homologue; three groups of eukaryotic and archaeal ribosomal proteins,
      namely L30e, L7Ae/S6e and S12e; an uncharacterized Bacillus subtilis protein
      related to the L7A/S6e group; and Escherichia coli ribosomal protein modification
      enzyme RimK. We hypothesize that a new type of RNA-binding domain may be utilized
      to deliver additional activities to the ribosome.

PMID- 7518075
TI  - Molecular evolution of SRP cycle components: functional implications.
AB  - Signal recognition particle (SRP) is a cytoplasmic ribonucleoprotein that targets
      a subset of nascent presecretory proteins to the endoplasmic reticulum membrane.
      We have considered the SRP cycle from the perspective of molecular evolution,
      using recently determined sequences of genes or cDNAs encoding homologs of SRP
      (7SL) RNA, the Srp54 protein (Srp54p), and the alpha subunit of the SRP receptor
      (SR alpha) from a broad spectrum of organisms, together with the remaining five
      polypeptides of mammalian SRP. Our analysis provides insight into the
      significance of structural variation in SRP RNA and identifies novel conserved
      motifs in protein components of this pathway. The lack of congruence between an
      established phylogenetic tree and size variation in 7SL homologs implies the
      occurrence of several independent events that eliminated more than half the
      sequence content of this RNA during bacterial evolution. The apparently non
      essential structures are domain I, a tRNA-like element that is constant in
      archaea, varies in size among eucaryotes, and is generally missing in bacteria,
      and domain III, a tightly base-paired hairpin that is present in all eucaryotic
      and archeal SRP RNAs but is invariably absent in bacteria. Based on both
      structural and functional considerations, we propose that the conserved core of
      SRP consists minimally of the 54 kDa signal sequence-binding protein complexed
      with the loosely base-paired domain IV helix of SRP RNA, and is also likely to
      contain a homolog of the Srp68 protein. Comparative sequence analysis of the
      methionine-rich M domains from a diverse array of Srp54p homologs reveals an
      extended region of amino acid identity that resembles a recently identified RNA
      recognition motif. Multiple sequence alignment of the G domains of Srp54p and SR
      alpha homologs indicates that these two polypeptides exhibit significant
      similarity even outside the four GTPase consensus motifs, including a block of
      nine contiguous amino acids in a location analogous to the binding site of the
      guanine nucleotide dissociation stimulator (GDS) for E. coli EF-Tu. The
      conservation of this sequence, in combination with the results of earlier genetic
      and biochemical studies of the SRP cycle, leads us to hypothesize that a
      component of the Srp68/72p heterodimer serves as the GDS for both Srp54p and SR
      alpha. Using an iterative alignment procedure, we demonstrate similarity between
      Srp68p and sequence motifs conserved among GDS proteins for small Ras-related
      GTPases. The conservation of SRP cycle components in organisms from all three
      major branches of the phylogenetic tree suggests that this pathway for protein
      export is of ancient evolutionary origin.

PMID- 7518081
TI  - Multiple myeloma: current treatment.

PMID- 7518082
TI  - Engineering a uniquely reactive thiol into a cysteine-rich peptide.
AB  - Cysteine mutagenesis for the purpose of chemical labelling was applied to the K+
      channel neurotoxin charybdotoxin, a 37-residue peptide with six functionally
      essential cysteines. An additional 'spinster cysteine' was introduced at a
      position far away in space from the toxin's known interaction surface where it
      contacts its K+ channel receptor. Despite the presence of the extra unpaired
      cysteine residue, the toxin still folds efficiently and may be labelled by
      fluorescent and radioactive reagents to give a functionally competent toxin.

PMID- 7518080
TI  - Palliative care. A model response.

PMID- 7518083
TI  - Modulation of enzyme activity by antibody binding to an alkaline phosphatase
      epitope hybrid protein.
AB  - An epitope from the HIV-1 gp120 protein V3 loop has been inserted onto the
      surface of bacterial alkaline phosphatase at different positions in the vicinity
      of the enzyme active site, creating hybrid proteins that can bind to an anti
      gp120 monoclonal antibody. One of the hybrid proteins, API1, has a 13 amino acid
      V3 loop sequence inserted between residues 407 and 408 of alkaline phosphatase.
      The enzymatic activity of this protein is modulated upon antibody binding. API1
      maintains the full activity of the wild type alkaline phosphatase but in the
      presence of the anti-gp120 antibody, the enzyme activity is inhibited by 40-50%.
      Thus, the hybrid enzyme can be used to detect the presence of antibody in
      solution. The concept of signalling proteins may have a wide application. Two
      models for the mechanism of modulation, steric hindrance and allosteric
      regulation, are discussed.

PMID- 7518084
TI  - Expression of immunoglobulin and scavenger receptor superfamily domains as
      chimeric proteins with domains 3 and 4 of CD4 for ligand analysis.
AB  - One approach to the analysis of leucocyte cell surface proteins is to express
      their domains with part of another protein as a carrier. We report the use of two
      immunoglobulin superfamily (IgSF) domains from rat CD4 (CD4d3 + 4) in producing
      domains from various superfamilies as chimeric proteins in Chinese hamster ovary
      cell lines. Four types of construct were successfully expressed containing: (i)
      the two IgSF domains of CD48; (ii) the IgSF domain of mb-1 which is part of the B
      cell antigen recognition complex; (iii) a T cell receptor V domain; and (iv) the
      N-terminal domain of CD5 which belongs to the scavenger receptor superfamily.
      This CD5 chimeric protein was antigenic for a panel of CD5 mAbs showing that mAbs
      with functional effects reacted with the N-terminal domain of CD5. The CD48
      chimeric protein has been used both as multivalent complexes produced by cross
      linking with mAbs recognizing CD4 and in a monomeric form to analyse the kinetics
      of the interaction between CD48 and CD2 [van der Merwe et al. (1993) EMBO J., 12,
      4945-4954].

PMID- 7518085
TI  - Serotonergic neurotoxic lesions facilitate male sexual reflexes.
AB  - The effects of the neurotoxin 5,7 dihydroxytryptamine (5,7 DHT) on the
      urethrogenital reflex was examined in anesthetized male rats. Both ICV and
      intrathecal administration of 5,7 DHT produced a marked depletion (92%) of spinal
      5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HT IAA) levels. ICV
      but not intrathecal administration of 5,7 DHT also caused a moderate reduction in
      5-HT and 5-HT IAA levels in the medulla and hypothalamus (40-48%). No reduction
      in adrenergic levels were observed. In spinally intact, vehicle-treated rats the
      urethrogenital reflex could not be evoked. However, the urethrogenital reflex
      could be evoked in rats pretreated with either ICV or intrathecal 5,7 DHT prior
      to section of the spinal cord. These data support the hypothesis that 5-HT
      mediates the descending inhibition of male sexual reflexes.

PMID- 7518087
TI  - Characteristics of IS401, a new member of the IS3 family implicated in plasmid
      rearrangements in Pseudomonas cepacia.
AB  - We have determined the nucleotide sequence of IS401, an insertion sequence
      implicated in rearrangements of a 170-kb cryptic plasmid from Pseudomonas
      cepacia. Our analysis focused on a 4066-bp plasmid fragment containing adjacent
      copies of IS401 and of IS408, an element reported previously to activate gene
      expression in P. cepacia. One objective was to determine if an apparent increase
      in the copy number of IS401 in strains carrying adjacent plasmid copies of these
      two elements might be due to readthrough transcription of an IS401 transposase
      gene from an outwardly directed promoter within IS408. This possibility was ruled
      out by nucleotide sequence analysis of the 4066-bp plasmid fragment, which
      indicated that the major open reading frames of IS401 were oriented in the
      direction of IS408. IS401 was 1316 bp in length and had 26-bp terminal inverted
      repeats flanked by 3-bp direct duplications of adjacent DNA. It was closely
      related to the IS3 family elements IS51 from P. savastanoi and IS3411 from
      Escherichia coli. Pertinent features of IS408 are also discussed.

PMID- 7518086
TI  - Penile erection and yawning induced by paraventricular NMDA injection in male
      rats are mediated by oxytocin.
AB  - The effect of N-methyl-D-aspartic acid (NMDA), (+-)-alpha-amino-3-hydroxy-5
      methyl-isoxazole-4-propionic acid (AMPA), or (+-)-trans-1-amino-1,3-cyclo
      pentanedicarboxylic acid (ACPD) (5-60 ng in 0.3 microliter of saline)
      microinjected in the paraventricular nucleus of the hypothalamus on penile
      erection and yawning was studied in male rats. NMDA induced both penile erection
      and yawning in a dose-dependent manner. AMPA and ACPD also induced penile
      erection but less potently than NMDA, but were ineffective in causing yawning.
      NMDA effect on penile erection and yawning was prevented by (+)-MK-801 (0.05-0.1
      mg/kg IP, 10 min before NMDA), by the oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-
      vasotocin (50-100 ng ICV 10 min before NMDA), but not by haloperidol (0.1-0.5
      mg/kg IP 10 min before NMDA). The results suggest that NMDA induces penile
      erection and yawning by increasing oxytocinergic transmission by acting in the
      paraventricular nucleus of the hypothalamus.

PMID- 7518088
TI  - Molecular cloning and expression of a new class of ortho-diphenol-O
      methyltransferases induced in tobacco (Nicotiana tabacum L.) leaves by infection
      or elicitor treatment.
AB  - In tobacco (Nicotiana tabacum L. cv Samsun NN), three distinct enzymes account
      for ortho-diphenol-O-methyltransferase (OMT) activity. OMT I is the major enzyme
      of healthy leaves, whereas enzymes OMT II and III are preferentially induced
      during the hypersensitive reaction to tobacco mosaic virus (TMV). Using an anti
      OMT III antiserum, we isolated a partial OMT III cDNA clone by immunoscreening an
      expression library made from mRNA of TMV-infected tobacco leaves. Using this OMT
      III clone as a probe, we isolated a full-length clone with a deduced amino acid
      sequence encompassing all of the sequences obtained by Edman degradation of both
      purified proteins II and III. Thus, OMT II and III of tobacco are likely to be
      encoded by the same genes and to arise from different posttranslational
      modifications. Sequence analysis showed that this OMT clone represents a new
      class of OMT enzymes (class II) with a low level of similarity (53-58%) to OMTs
      cloned previously from other dicotyledonous plants. Southern analysis indicated
      that a small family of class II OMT genes inherited from ancestors related to
      Nicotiana sylvestris and Nicotiana tomentosiformis occurs in the tobacco genome.
      RNA blot analysis demonstrated that class II OMT genes, unlike class I OMT genes,
      are not expressed at a high constitutive level in lignified tissues of tobacco.
      Class II OMT transcripts were found to accumulate in tobacco leaves infected with
      TMV or treated with megaspermin, a proteinaceous elicitor from Phytophthora
      megasperma, but not in leaves treated with salicylic acid, a molecule known to
      trigger many defense genes. In TMV-infected or elicitor-treated tissues, a marked
      increase in catechol-methylating activity accompanied the accumulation of class
      II OMT gene products.

PMID- 7518090
TI  - Involvement of intracellular calcium in anaerobic gene expression and survival of
      maize seedlings.
AB  - Ca-mediated processes are known to be involved in transducing many developmental,
      hormonal, and environmental cues in plant cells. In this study, the role of Ca in
      the perception of anoxic stress signals by maize (Zea mays L. cv B73) roots was
      assessed by studying the effect of various Ca antagonists on the induction of
      alcohol dehydrogenase (ADH) and sucrose synthase mRNA as well as ADH activity
      under anoxia. The effect of these compounds on the poststress recovery of the
      seedlings was also monitored. Ruthenium red (RR), an inhibitor of organellar Ca
      fluxes, repressed the anoxic activation of the alcohol dehydrogenase1 and
      shrunken1 genes as measured by their transcript levels as well as ADH activity.
      Furthermore, RR-treated seedlings could not recover even after only 2 h of
      flooding, in contrast to untreated B73 seedlings that survived 72 h of
      submergence. Ca, when supplied along with RR, allowed normal anoxic gene
      expression and also prevented the RR-imposed death of the seedlings from short
      term anoxia. Ca (45Ca) fluxes were measured in maize roots to elucidate the mode
      of action of RR. RR abolished anoxia-stimulated 45Ca influx into maize roots but
      did not affect aerobic Ca2+ uptake, unlike a few other antagonists that blocked
      both the aerobic and anoxic fluxes. However, Ca uptake across the plasma membrane
      was not necessary for the adaptive response to anoxia, since chelation of
      extracellular Ca by ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic
      acid or 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid did not affect
      the induction of ADH activity or poststress survival of flooded seedlings. The
      data suggest that RR may act on one of the intracellular stores of Ca and the Ca
      mobilized from this source is a physiological transducer of anoxic stress signals
      in maize roots.

PMID- 7518091
TI  - Aquaporins: the molecular basis of facilitated water movement through living
      plant cells?

PMID- 7518089
TI  - Identification, cDNA cloning, and gene expression of soluble starch synthase in
      rice (Oryza sativa L.) immature seeds.
AB  - Three forms of soluble starch synthase were resolved by anion-exchange
      chromatography of soluble extracts from immature rice (Oryza sativa L.) seeds,
      and each of these forms was further purified by affinity chromatograph. The 55-,
      57-, and 57-kD proteins in the three preparations were identified as candidates
      for soluble starch synthase by western blot analysis using an antiserum against
      rice granule-bound starch synthase. It is interesting that the amino-terminal
      amino acid sequence was identical among the three proteins, except that the 55-kD
      protein lacked eight amino acids at the amino terminus. Thus, these three
      proteins are products of the same gene. The cDNA clones coding for this protein
      have been isolated from an immature rice seed library in lambda gt11 using
      synthetic oligonucleotides as probes. The deduced amino acid sequence of this
      protein contains a lysine-X-glycine-glycine consensus sequence for the ADP
      glucose-binding site of starch and glycogen synthases. Therefore, we conclude
      that this protein corresponds to a form of soluble starch synthase in immature
      rice seeds. The precursor of the enzyme contains 626 amino acids, including a 113
      residue transit peptide at the amino terminus. The mature form of soluble starch
      synthase shares a significant but low sequence identity with rice granule-bound
      starch synthase and Escherichia coli glycogen synthase. However, several regions,
      including the substrate-binding site, are highly conserved among these three
      enzymes. Blot hybridization analysis demonstrates that the gene encoding soluble
      starch synthase is a single-copy gene in the rice genome and is expressed in both
      leaves and immature seeds. These results suggest that soluble and granule-bound
      starch synthases play distinct roles in starch biosynthesis of plant.

PMID- 7518093
TI  - Modeling for risk assessment of neurotoxic effects.
AB  - The regulation of noncancer toxicants, including neurotoxicants, has usually been
      based upon a reference dose (allowable daily intake). A reference dose is
      obtained by dividing a no-observed-effect level by uncertainty (safety) factors
      to account for intraspecies and interspecies sensitivities to a chemical. It is
      assumed that the risk at the reference dose is negligible, but no attempt
      generally is made to estimate the risk at the reference dose. A procedure is
      outlined that provides estimates of risk as a function of dose. The first step is
      to establish a mathematical relationship between a biological effect and the dose
      of a chemical. Knowledge of biological mechanisms and/or pharmacokinetics can
      assist in the choice of plausible mathematical models. The mathematical model
      provides estimates of average responses as a function of dose. Secondly,
      estimates of risk require selection of a distribution of individual responses
      about the average response given by the mathematical model. In the case of a
      normal or lognormal distribution, only an estimate of the standard deviation is
      needed. The third step is to define an adverse level for a response so that the
      probability (risk) of exceeding that level can be estimated as a function of
      dose. Because a firm response level often cannot be established at which adverse
      biological effects occur, it may be necessary to at least establish an abnormal
      response level that only a small proportion of individuals would exceed in an
      unexposed group. That is, if a normal range of responses can be established, then
      the probability (risk) of abnormal responses can be estimated.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7518092
TI  - Detection of glioma-associated gangliosides GM2, GD2, GD3, 3'-isoLM1 3',6'-isoLD1
      in central nervous system tumors in vitro and in vivo using epitope-defined
      monoclonal antibodies.
AB  - In this study, MAbs to the 'conventional' gangliosides expressed by human gliomas
      were generated and used to detect ganglioside species previously unisolated or
      defined in normal adult CNS tissue. Despite the marked phenotypic and genotypic
      heterogeneity shown by glioma cell lines (Bigner et al., 1981), the ganglioside
      phenotype of these cell lines is remarkably consistent qualitatively, if not
      quantitatively, in the ganglioside species expressed (Table V). The majority of
      cell lines and tumor samples express GM2, GD2 and GD3; this does not provide a
      diagnostic advantage (Vick et al., 1992). Nevertheless, as the relative amounts
      of these gangliosides in tumor as compared with normal adult CNS tissue is
      considerable, such reagents might be considered in compartmental
      immunotherapeutic approaches. Since GD2 and GD3 have been determined to mediate
      tumoricidal activity with human effector cells via specific antiganglioside
      epitope MAbs (Thurin et al., 1987; Kushner and Cheung, 1991; Barker et al., 1991;
      Reisfeld, 1993), cell-mediated approaches, as well as targeted immunoglobulin
      therapies, are also possible. The prospect of a more targeted approach with
      little or no effect on normal CNS tissue is now possible via the 'oncofetal'
      epitopes characteristic of 3'-isoLM1 and 3',6'-isoLD1. Several factors recommend
      the use of these moieties for compartmental immunotherapy; the inability to
      detect them within the adult CNS; the relatively high frequency of expression of
      3'-isoLM1 and 3',6'-isoLD1, especially in human tumor samples (50-100%, depending
      upon the series and assay); and the existence of specific MAbs reactive with
      these epitopes. Current technology is being applied to these MAbs to transfer the
      specific recognition capacity of existing murine MAbs into various human
      framework structures of any desired immunoglobulin class, and thereby, biologic
      function. The variety of effector functions, the stability in affinity, labeling
      capacity, and the exquisite sensitivity of these MAbs for these glioma
      distinctive epitopes is an exciting and promising approach for immunotherapy of
      human CNS tumors.

PMID- 7518094
TI  - [The clinical relevance of autoantibody studies in connective tissue diseases and
      vasculitis].
AB  - The relevance of detection, quantification and characterisation of antinuclear
      antibodies and of anti-neutrophil cytoplasm antibodies in diagnosis of connective
      tissue disorders and of idiopathic vasculitis, is nowadays quite important. Since
      many years, antibody detection is routinely performed by indirect
      immunofluorescence tests; their sensitivity is very high so that several
      diagnoses might be ruled out in the presence of a negative result. These tests
      are however not specific. During the last years several progress have been
      realised in the characterisation of the antigens recognized by these antibodies,
      allowing the development of new techniques for specifically identifying several
      autoantibodies. It is therefore possible to detect now routinely with specific
      and sensitive techniques the presence of anti-double stranded DNA, anti-RNP, anti
      Sm, anti-Scl-70, anti-SS-A, anti-SS-B, and anti-myeloperoxidase and anti
      proteinase 3. The significance of the presence of these antibodies in serum will
      be discussed in this paper.

PMID- 7518095
TI  - [Segmental anatomy teaching through imaging methods in a medical graduate course:
      material preparation and didactic techniques].

PMID- 7518096
TI  - Formation of healing tissue and angiogenesis in repair of connective tissue
      stimulated by epidermal growth factor.
AB  - Epidermal growth factor (EGF) has been shown to stimulate connective tissue
      repair in the perforated mesentery of rats. The aim of the present investigation
      was to study the effect of EGF on the formation of healing tissue and
      angiogenesis in such repair. After laparotomy standardised perforations were made
      in the centre of the mesenteric "windows" with a scalpel. The rats were given
      intraperitoneal injections of either 10 micrograms EGF dissolved in phosphate
      buffered saline (PBS), or PBS alone, twice daily for four consecutive days
      beginning on the day of operation. In the first experiment, healing tissue
      formation and angiogenesis was quantified morphometrically in perpendicularly cut
      mesenteric windows on days 1 to 10 after operation. Treatment with EGF caused the
      formation of significantly more healing tissue on days 2 to 7, but no stimulation
      of angiogenesis. In the second experiment, angiogenesis was quantified
      morphometrically on days 14 and 21. Mesenteric windows were spread out on
      objective slides after the capillary bed had been visualised by perfusion of
      carbon ink. Perforation caused a significant increase of microvascular density in
      the centre of the mesenteric windows on days 14 and 21. Treatment with EGF did
      not stimulate angiogenesis at any observation point. In conclusion, treatment
      with EGF significantly increased the formation of healing tissue in connective
      tissue repair in the perforated mesentery of rats, but did not affect
      angiogenesis.

PMID- 7518098
TI  - Collagen induces normal signal transduction in platelets deficient in CD36
      (platelet glycoprotein IV).
AB  - The receptor involved in platelet activation by collagen has not been identified.
      Platelet glycoprotein IV, now known as CD36, has been implicated in interaction
      with collagen and also been shown to be associated with intracellular tyrosine
      kinases. In order to investigate the possible role of collagen-mediated signal
      transduction via CD36, platelets were obtained from a donor that were deficient
      in CD36. The collagen-induced intracellular mobilization of Ca2+ in the CD36
      deficient cells was of the same magnitude as that seen in platelets from normal
      donors. In addition, serotonin secretion did not appear to be impaired. Tyrosine
      phosphorylation was also comparable between the CD36-deficient and normal
      platelets. Thus, it is unlikely that CD36 plays a major role in collagen
      dependent platelet signal transduction.

PMID- 7518097
TI  - [Prognostic factors in resected stomach carcinoma].
AB  - Between January 1982 and December 1991, 232 consecutive patients (121 male, 111
      female) with gastric adenocarcinoma were treated at our clinic. Resection of the
      tumors (resectability 73.7%) included lymphadenectomy of compartment I (D1
      resection). The tumors were classified according to the Borrmann's and Lauren's
      criteria and according to the TNM system. 171 patients underwent resection of the
      tumor, 49 palliative surgery and 12 were treated nonsurgically. The operative
      morbidity in patients with resection and palliative operations was 20.5% and
      10.2% respectively, and the mortality rate was 0.6% and 8.2% respectively. Follow
      up data (median 6 years postoperatively) were available for 229 out of 232
      patients (98.7%). After resection, the five year actuarial survival rate
      according to the method of Kaplan-Meier was 38.2%. The probability of survival
      increased to 47.5% after potentially curative resection. An univariate and a
      multivariate analysis by the proportional hazard model (Cox regression analysis)
      identified several significant prognostic parameters for survival (in order of
      their significance): tumor stage (TNM), N-stage, percentage of positive lymph
      node metastases among removed nodes, Borrmann criteria, T-stage, metastases in
      five and more lymph nodes, diameter of the tumor, serosal involvement, peritoneal
      and hepatic metastases, and patient's age. The following parameters did not have
      a prognostic value in our analysis: grading, Lauren classification, and
      localization of the tumor. We conclude that the identification of several
      prognostic factors allows us to estimate the probability of survival for each
      individual patient. In future these factors may influence decision-making on
      adjuvant treatment of gastric cancer.

PMID- 7518099
TI  - Effect of low molecular weight heparin, dextran and their combinations on
      experimental venous thrombosis in rabbits.
AB  - An experimental model based on the combination of endothelial damage and flow
      reduction was used to induce jugular vein thrombosis in rabbits. The effect on
      thrombosis of a low molecular weight heparin (LMWH [Fragmin]), dextran 70,
      placebo and their combination was studied in a double-blind fashion with actual
      doses used in clinical thromboprophylaxis. Saline and polygeline were used as
      placebo in the control group. Four groups with 120 isolated vein segments in 60
      animals were studied for presence of thrombus formation, occlusive thrombi and
      thrombus weights. Dextran reduced the thrombus weights (p = 0.048) and the
      formation of occlusive thrombi (p = 0.01), but not the formation of thrombi when
      compared with the placebo control group. Similarly, LMWH reduced the thrombus
      weights (p = 0.046), the formation of thrombi (p = 0.007) and occlusive thrombi
      (p = 0.0001). Compared with the LMWH group the group treated with the combination
      of LMWH and dextran was found to reduce the frequency of occlusive thrombi (p =
      0.03) and numerically, but not significantly, further reduce the overall
      frequency of thrombosis (p = 0.18) and thrombus weights (p = 0.11). The results
      are consistent with an augmentation of the antithrombotic effect of LMWH by
      dextran 70. The need for further evaluation of the combined efficacy of LMWH and
      dextran is apparent from this study.

PMID- 7518100
TI  - Coagulopathy caused by intrauterine dextran.

PMID- 7518101
TI  - Charcot-Marie-Tooth disease: a new paradigm for the mechanism of inherited
      disease.
AB  - Recent work has identified the genes and mutational mechanisms that underlie
      several inherited diseases of the peripheral nervous system and has provided both
      the first genetic rationale for classification of these disorders and an insight
      into their biological basis. These studies have yielded some surprising findings,
      including the discovery that two very different mutational mechanisms
      (duplication and point mutation) can result in a similar clinical phenotype in
      Charcot-Marie-Tooth disease type 1A, and that mutations involving the same gene
      can give rise to different clinical phenotypes.

PMID- 7518102
TI  - Combination therapy with FK 506 and splenectomy may induce tolerance in cardiac
      xenografts.

PMID- 7518103
TI  - Lymphocyte subset monitoring can detect xenoheart rejection in primates.

PMID- 7518104
TI  - Coordinate functions of multiple complement regulating molecules, CD46, CD55, and
      CD59.

PMID- 7518105
TI  - Cardiac xenotransplantation from pig to Japanese monkey with splenectomy,
      tacrolims, filtration plasmapheresis, and nafamstat mesilate.

PMID- 7518106
TI  - Morphologic evaluation of xenotransplanted neonatal islets of Langerhans and
      fetal pancreata from rats to nude mice.

PMID- 7518107
TI  - Human mononuclear cell adhesion to porcine arterial endothelium.

PMID- 7518108
TI  - Retinoic acid inhibits expression of E-selectin in endothelial cells and prolongs
      discordant xenograft survival.

PMID- 7518110
TI  - Mechanism of antibody production in hamster-to-rat concordant
      xenotransplantation: establishment of a simple model using intravenous injection
      of concordant splenocytes.

PMID- 7518109
TI  - Effect of splenectomy on hamster-to-rat pancreas xenotransplantation.

PMID- 7518112
TI  - Pretransplant xenogeneic blood transfusion combined with FK 506 prolongs hamster
      to-rat liver xenograft survival.

PMID- 7518111
TI  - Mechanisms of hamster kidney graft rejection in the rat.

PMID- 7518113
TI  - FK 506 prolongs survival of liver but not heart mouse-to-rat vascularized
      xenografts.

PMID- 7518115
TI  - Cell- and tissue-specific expression of a human CD59 minigene in transgenic mice.

PMID- 7518114
TI  - Possibility of prevention of hyperacute rejection by DAF and CD59 in
      xenotransplantation.

PMID- 7518117
TI  - Erythroid-specific expression of human CD59 and transfer to vascular endothelial
      cells.

PMID- 7518116
TI  - Demonstration of intermembrane transfer of CD59 during coculture of human
      erythrocytes with porcine and bovine aortic endothelial cells.

PMID- 7518118
TI  - Expression of complement regulatory factors using heterologous promoters in
      transgenic mice.

PMID- 7518119
TI  - Inhibition of species-specific complement-mediated cytolysis in xenoendothelial
      cells transfected with GPI-anchored complement regulatory factor (DAF, HRF20)
      gene using retroviral vector: comparison between single (DAF or HRF20) and double
      (DAF and HRF20) transfected xenoendothelial cells.

PMID- 7518120
TI  - Ex vivo perfusion of mouse hearts expressing the human complement regulatory
      protein CD59.

PMID- 7518121
TI  - Protection from complement-mediated cytolysis in cross-species hepatocytes
      transfected with complement regulatory factor (HRF20) using retroviral vector.

PMID- 7518122
TI  - Effect of transfectant molecules, MCP, DAF, and MCP/DAF hybrid on xenogeneic
      vascular endothelium.

PMID- 7518124
TI  - Enhancement of the complement regulatory function of CD59 by site-directed
      mutagenesis at the N-glycosylation site.

PMID- 7518128
TI  - Selective inhibition of E-selectin expression by alpha-globulins.

PMID- 7518125
TI  - Enzymatic removal from various tissues of the galactose alpha 1,3-galactose
      target antigens of human antispecies antibodies.

PMID- 7518126
TI  - Synergistic effect of donor pretreatment using FK 506 in hamster-to-rat cardiac
      xenotransplantation.

PMID- 7518129
TI  - Clinical potential of xenotransplantation.

PMID- 7518127
TI  - Introduction and expression of human CD59 gene in the canine kidney.

PMID- 7518130
TI  - Mechanism of antibody production in guinea pig to rat discordant xenotransplant:
      establishment of a simple model by intravenous injection of discordant
      splenocytes.

PMID- 7518132
TI  - An approach to the structure of carbohydrate epitopes recognized by human natural
      antibodies on porcine endothelial cells.

PMID- 7518131
TI  - Confirmation of a major target epitope of human natural IgG and IgM anti-pig
      antibodies: terminal galactose alpha -1,3-galactose.

PMID- 7518134
TI  - Production of pigs transgenic for human decay accelerating factor.

PMID- 7518133
TI  - Human naturally occurring antibodies to pig xenografts.

PMID- 7518123
TI  - Complement and target cells belong to the same species after liver xenografting:
      protection from hyperacute rejection.

PMID- 7518135
TI  - Expression of human decay accelerating factor in transgenic pigs.

PMID- 7518137
TI  - Lymphoproliferative disease after intestinal transplantation under primary FK 506
      immunosuppression.

PMID- 7518136
TI  - Intestinal transplantation at the University of Pittsburgh.
AB  - Our experience with clinical intestinal transplantation under FK 506
      immunosuppression showed that 50% of the recipients were able to be independent
      from TPN after transplantation, but 10% require partial TPN with functioning
      grafts, 10% needed total TPN after graft removal, and 30% of the recipients died
      postoperatively, mostly from sepsis due to severe graft rejection. For further
      improvement in patient survival and in the quality of life for patients after
      intestinal transplantation, it is mandatory to establish a new strategy for
      treatment and prevention of graft rejection and systemic infection.

PMID- 7518138
TI  - Effects of total parenteral nutrition on intestinal morphology and function in
      humans.

PMID- 7518139
TI  - Small bowel transplantation in sensitized recipients: comparison with heart,
      kidney, and liver grafts.

PMID- 7518140
TI  - Effects of preformed antibodies induced by whole blood transfusion on small bowel
      transplantation.

PMID- 7518141
TI  - Monitoring of intestinal myoelectrical activity after isolated small bowel
      transplantation in FK 506 immunosuppressed pigs.

PMID- 7518142
TI  - Morphology of acute rejection and observation of lymphoproliferative hyperplastic
      reaction in FK 506 treated pigs after small bowel transplantation.

PMID- 7518143
TI  - The maltose absorption test does not predict allograft rejection of small bowel
      transplantation in FK 506 immunosuppressed pigs.

PMID- 7518144
TI  - CD44 expression on enterocytes: an indicator of rejection following rat small
      bowel transplantation.

PMID- 7518145
TI  - Detection of allograft rejection in rat small bowel transplantation by analysing
      the in situ distribution of S-phase lymphocytes.

PMID- 7518146
TI  - Serum cytokine levels after small bowel transplantation in pigs.

PMID- 7518147
TI  - Effect of FK 506 in combination with prednisolone on the graft-vs-host reaction
      after small bowel transplantation in rats.

PMID- 7518148
TI  - Total orthotopic small bowel transplantation in swine under FK 506.

PMID- 7518149
TI  - FK 506 in small bowel transplant recipients: pharmacokinetics and dosing.

PMID- 7518150
TI  - Intraportal donor-specific transfusion given 24 hours before small bowel
      transplantation with cyclosporine and FK 506.

PMID- 7518151
TI  - Alteration of the enteric nervous system and gut peptides following small bowel
      transplantation in rats.

PMID- 7518153
TI  - Infectious complications after small bowel transplantation in adults.

PMID- 7518154
TI  - Bacterial translocation and the role of postoperative selective bowel
      decontamination in small intestinal transplantation.

PMID- 7518152
TI  - Transplantation of the newborn rat intestine.

PMID- 7518155
TI  - Infectious complications in experimental small bowel transplantation.

PMID- 7518156
TI  - Development of type II diabetes after combined kidney-pancreas transplantation in
      a patient with type I (insulin-dependent) diabetes.

PMID- 7518157
TI  - Does alpha 1 microglobulin in urine predict renal function after transplantation?

PMID- 7518158
TI  - C-reactive protein and alpha 2 macroglobulin in urine as markers of renal
      transplant rejection.

PMID- 7518159
TI  - Chronic nephrotoxicity of FK 506 after liver transplantation.

PMID- 7518160
TI  - Whole blood and plasma levels of FK 506 after liver transplantation: correlation
      with toxicity.

PMID- 7518161
TI  - Influenza virus M2 protein ion channel activity is not required to maintain the
      equine-1 hemagglutinin in its native form in infected cells.
AB  - The equine-1 influenza virus A/Cornell/74 (H7N7) hemagglutinin (HA) is cleaved to
      HA1 and HA2 in the trans Golgi network (TGN) of infected cells. The avian
      influenza virus A/chicken/Germany/34 (fowl plague virus Rostock) H7 HA is also
      cleaved to HA1 and HA2 intracellularly in the TGN. To maintain the fowl plague
      virus Rostock HA in its native form during transport through the TGN, a
      functioning M2 ion channel activity is required, otherwise the HA undergoes its
      transition to the low-pH form (Sugrue et al., 1990, EMBO J. 9, 3469-3476).
      Studies were initiated to investigate if the equine H7 HA has intracellular
      requirements different from those of the fowl plague virus Rostock HA. We report
      here that the pH of transition to the low-pH form of the equine-1 HA is
      approximately pH 5.3 and that the M2 protein ion channel blocker, amantadine,
      does not have a discernable effect on the native conformation of equine-1 HA
      during transport through the TGN. Moreover, the equine-1 HA expressed from cDNA
      does not require coexpression of a functional M2 protein to maintain HA in its
      native conformation.

PMID- 7518162
TI  - A satellite RNA associated with bamboo mosaic potexvirus.
AB  - A small RNA molecule with properties of a satellite RNA was found in an isolate
      of bamboo mosaic potexvirus (BaMV-V) from Bambusa vulgaris McClure. This RNA
      (sBaMV RNA) and the genomic RNA of BaMV shared no significant sequence homology
      as assessed by hybridization with cDNA probes derived from the genomes of BaMV
      and sBaMV RNA. Replication of sBaMV RNA in barley protoplasts or Chenopodium
      quinoa was supported by BaMV, but not by potato virus X, the type member of the
      potexvirus group, or other unrelated viruses. The complete nucleotide sequence of
      sBaMV RNA is 836 nucleotides (excluding the poly(A) tail) and contains an open
      reading frame which starts after a 159-nucleotide 5'-untranslated region and
      encodes a 20,154-mol wt protein. In an in vitro rabbit reticulocyte lysate
      system, sBaMV RNA directed the synthesis of a protein estimated to be 25 kDa by
      SDS-polyacrylamide gel electrophoresis. The sBaMV RNA-encoded protein was not
      immunoprecipitated with antiserum against BaMV capsid protein. However, the sBaMV
      RNA was encapsidated with BaMV capsid protein to form rod-shaped particles with
      an average length of 60 nm as shown by immunoelectron microscopy. This is the
      first satellite RNA found in the potexvirus group.

PMID- 7518163
TI  - Human papillomavirus type 1 E4 protein is a zinc-binding protein.
AB  - Study of the human papillomavirus (HPV) E4 gene product has focused largely on
      HPV type 1 (HPV 1) primarily because of the large quantities of protein that can
      be purified from HPV 1-induced warts. We have extended the characterization of
      the HPV 1 E4 protein and, in this study, have shown that protein purified from
      clinical material and a heterologous expression system contains the divalent
      metal ion zinc. Furthermore, using a [65Zn]Cl2 dot-blot assay, we have shown that
      this binding is specific for zinc and those divalent cations that are known to
      structurally substitute zinc in metalloproteins. Mutational analysis has
      demonstrated that histidine amino acids (residues 56, 86, and 121), but not the
      cysteine residue (115), are essential for the zinc-binding activity of the E4
      protein. Two assayable functions of E4 are dimerization and the formation of
      E4/cytokeratin structures in cultured cells; however, neither activity is
      abrogated by the loss of zinc binding.

PMID- 7518165
TI  - Patterns of HIV-1 mRNA expression in transgenic mice are tissue-dependent.
AB  - To explore tissue-specific factors that may be important in HIV-1 transcriptional
      and post-transcriptional regulation, we examined a transgenic mouse model
      containing a mutant provirus deleted in the gag and pol region. The level of
      transgene expression was tissue-dependent. Skin, muscle, and tail consistently
      expressed the transgene abundantly; intestine, kidney, and thymus exhibited
      variable but generally low levels of expression; while liver expression was
      undetectable by Northern analysis. Individual mRNAs within the family of singly
      and multiply spliced messages were determined by reverse transcription (rt) of
      RNA samples from mouse tissues, polymerase chain reaction (PCR) amplification,
      and Southern hybridization with exon-specific probes. The exact percentage of Tat
      coding mRNA that was multiply spliced was also determined by competitive rtPCR.
      When 2-, 4-, or 7-kb (full-length) mRNA species were calculated as a percentage
      of the total mRNA, two phenotypes of distribution were detected. Lymphoid tissue
      (thymus and spleen) and kidney had significantly greater amounts of unspliced
      message (P < 0.001) regardless of the level of expression. All other tissues
      expressed the multiply spliced messages encoding Tat, Rev, and Nef predominantly.
      Furthermore, utilization of the three major second exon splice acceptor sites for
      tat, rev, and nef was the same in transgenic mice as has been demonstrated in
      human cells but the splice acceptor site for the vpu/env was different in murine
      tissue. The marked tissue-dependent patterns of HIV mRNA expression suggest a
      potential mechanism for the organ-specific manifestations of AIDS.

PMID- 7518164
TI  - Localization of a neutralizing epitope on the envelope protein of dengue virus
      type 2.
AB  - Two neutralization-resistant variants of dengue virus type 2 were selected using
      the neutralizing monoclonal antibody G8D11. Virus N-GV4 was derived from the New
      Guinea C strain and virus P-GV3 from the PUO-218 strain. Both variants had an
      identical change at nucleotide 919 in the E gene, causing a substitution of
      glutamic acid for lysine at residue 307 in the E glycoprotein. The substitution
      abolished the ability of antibody G8D11 to bind to the E glycoprotein in
      radioimmunoprecipitation experiments. The epitope was sensitive to treatment with
      SDS and was dependent on the formation of a disulfide bridge. This dependency was
      determined by mutagenesis of Cys residues 11 and 12 in the E glycoprotein.

PMID- 7518166
TI  - Association of a retrovirus with a wasting condition in the Swedish moose.
AB  - A wasting disease in moose (Alces alces) has killed more than one thousand
      animals in a densely populated, limited geographical area in Sweden. To
      investigate the cause, local environmental conditions were studied and infectious
      agents, mainly viruses, were looked for. A virus, identified as a retrovirus, has
      repeatedly been isolated from diseased animals by cocultivation of their
      leukocytes with fetal moose kidney cells. The virus has the characteristics of a
      member of the Oncovirinae subfamily, as deduced from its morphology from EM
      studies, reverse transcriptase activity, cell transforming properties, and
      serological cross-reactivity with other oncoviruses. Striking features of the
      disease are the poor and transient capacity of affected moose to respond
      serologically in addition to the frequent presence of high levels of reverse
      transcriptase activity in their sera.

PMID- 7518167
TI  - The chicken Mx promoter contains an ISRE motif and confers interferon
      inducibility to a reporter gene in chick and monkey cells.
AB  - Genomic DNA containing the first four exons and upstream sequences of the
      interferon (IFN)-inducible chicken Mx gene was cloned and sequenced. The
      exon/intron structure of the chicken Mx gene resembles that of the mouse Mx1
      gene: exon 1 is very small, the first intron contains a noncoding exon 1' that is
      alternatively spliced in different chicken breeds and exon 2 harbors the ATG
      initiation codon. Exons 3 and 4 of the chicken and mouse Mx genes have identical
      lengths and the encoded polypeptides show a high degree of homology. Sequences
      upstream of the transcription start site functioned as an IFN-inducible promoter
      in chick and monkey cells when cloned in front of a promoterless luciferase
      reporter gene. Deletion analysis suggested that the sequence 5'AGTTTCGTTTCT3' is
      of critical importance for inducibility. It conforms to the consensus sequence of
      the IFN-stimulated response element (ISRE) present in Mx and other IFN-alpha/beta
      inducible promoters of mammals. These results suggest that the ISRE motif has
      been conserved and that it regulates expression of IFN-inducible genes in both
      mammals and birds.

PMID- 7518168
TI  - Serotype-specific and canine distemper virus cross-reactive H-2Kk-restricted
      cytotoxic T lymphocyte epitopes in the measles virus nucleoprotein.
AB  - Immunization of C3H mice with a vaccinia virus (VV) recombinant expressing the
      measles virus (MV) nucleoprotein (NP) induces an H-2Kk-restricted cytotoxic T
      lymphocyte (CTL) response. With reference to the predicted peptide epitope motifs
      binding to this MHC class I molecule, we have used synthetic peptides derived
      from the primary sequence of the MV NP to establish the identity of the Kk
      restricted CTL epitopes. Two octameric peptides, LDRLVRLI (aa 52-59) and VESPGQLI
      (aa 81-88) sensitized P815-Kk cells to lysis by MV NP-induced CTLs. In contrast
      to LDRLVRLI, the sequence VESPGQLI is also present in the primary sequence of the
      NP from the closely related canine distemper virus (CDV). In vitro stimulation of
      spleen cells from VV NP-immunized mice with the peptides showed that peptide
      VESPGQLI induced CTLs which could also lyse CDV-infected cells, whereas peptide
      LDRLVRLI could only lyse cells presenting the MV protein. Different
      concentrations of peptides were used, and the lysis efficiencies for both
      epitopes were shown to be of the same order. The value of predicative motifs for
      determining MHC class I CTL epitopes is discussed.

PMID- 7518169
TI  - [Sexual disorders in patients with prostatic adenoma combined with chronic
      prostatitis and without].
AB  - Data obtained by the authors evidence that patients with adenoma of prostate have
      variously pronounced sexual disorders which are more frequent and marked at the
      background of chronic prostatitis. Adenomectomy promotes sexual function but its
      effect is insignificant in patients with concomitant chronic prostatitis.
      Conservative treatment improves sexual function, mostly in patients with chronic
      prostatitis but fails in its association with adenoma.

PMID- 7518170
TI  - [The clinical diagnosis and treatment of meningitis caused by Coxsackie B
      viruses].
AB  - Clinical features of meningitis caused by Coxsackie virus B were analyzed in 369
      adult patients. The authors draw attention to polymorphism of manifestation and
      diagnostic signs of the diseases. Reaferon used in complex treatment was
      established to be the most effective. The drug considerably shortened period of
      fever and drove away main clinical symptoms.

PMID- 7518172
TI  - Analysis of the antigenic profile of measles virus haemagglutinin in mice and
      humans using overlapping synthetic peptides.
AB  - In this study, a panel of 55 synthetic peptides representing 92.2% of the
      haemagglutinin (H) glycoprotein of measles virus (MV) were used to study the
      antigenic profile of the H molecule of anti-MV antibodies raised in mice and late
      convalescent human sera. In addition the immunogenicity of these peptides was
      tested in two mouse strains. Mouse anti-MV antibodies had different fine
      specificity of binding to the peptides depending on the mouse strain. Thus in
      BALB/c (H-2d) mice, anti-MV antibodies recognised six peptides representing
      residues 103-117; 123-137; 242-255; 293-307 and 463-477. In TO (H-2s) mice, anti
      MV antibodies recognised peptides representing residues 49-72 and 463-477. When
      the immunogenicity of the peptides was tested, 29 were immunogenic in BALB/c mice
      and 34 were immunogenic in TO mice. Several of the anti-peptide antisera were
      found to cross-react with MV, depending on the solid phase assay system used but
      none were able to inhibit virus infectivity in vitro. The reactivity of a panel
      of late convalescent human sera with the peptides was heterogeneous and the
      extent of the binding to the peptides was related to the titre of anti-MV.
      However, human sera recognized certain peptides more frequently than others, in
      particular peptides at the carboxyl-terminus.

PMID- 7518173
TI  - Immunohistochemical detection of substance P and vasoactive intestinal peptide
      fibres in the auricular lymph nodes of sensitized guinea pigs and mice.
AB  - The presence of substance P (SP) and vasoactive intestinal peptide (VIP) in
      auricular lymph nodes of normal and sensitized guinea pigs and mice has been
      investigated using polyclonal antibodies directed against these neurotransmitters
      and the unlabelled peroxidase-antiperoxidase procedure. Positive immunoreactivity
      could be observed only in draining lymph nodes of sensitized animals. SP
      immunoreactivity was found in mice and guinea pigs but a VIP-positive reaction
      only in mice. The immunopositive sites were always associated with blood vessels.
      The present study suggests that the neurotransmitters SP and VIP are involved in
      mechanisms of sensitization taking place in secondary lymphoid organs.

PMID- 7518174
TI  - Morphometric analysis of cultured normal and cardiomyopathic hamster heart cells
      after immunofluorescent staining for tubulin and alpha-actinin.
AB  - The cardiomyopathic (CM) hamster (Strain UM X7.1) develops a progressive
      cardiomyopathy characterized by cellular necrosis, hypertrophy and congestive
      heart failure. To better understand these abnormalities, this study was
      undertaken to investigate possible abnormalities in the morphology and
      distributions of cytoskeletal proteins in normal and cardiomyopathic hamster
      heart cells in vitro. Primary cultures of cardiac myocytes from normal and CM
      newborn hamsters were analyzed and compared by indirect immunofluorescent
      microscopy after 3, 5, 7 and 9 days in culture. The distributions of the
      cytoskeletal proteins, alpha-actinin and tubulin, were examined in cultured
      hamster cardiac myocytes. After the cells attach to coverslips, both normal and
      CM myocytes appear rounded in shape. After 5 days in culture, CM myocytes show
      fewer cytoplasmic projections than normal. To assess this phenomenon, the area
      and perimeter dimensions of normal and CM myocytes were analyzed by morphometric
      methods. It was determined that cardiomyopathic cells in culture become
      progressively larger in area but smaller than normal in their perimeter
      dimensions. A statistically significant difference was noted from day 3 onward.
      This result confirms that cardiomyopathic cells have abnormal shapes in vitro. It
      is conceivable that a reduction of the perimeter dimension in CM cells may be
      related to the reported calcium overload or to other biochemical or physiological
      lesions. In addition, the greatest density of tubulin staining is present
      immediately around the nucleus, with fluorescent "rays" radiating out to the cell
      periphery. Most of the myofibrils labelled by anti-alpha-actinin antibody showed
      parallel arrangements with respect to each other in normal myocytes whereas in CM
      heart cells the myofibrils were disarrayed. There were no differences in the
      distributions of tubulin and alpha-actinin in normal and cardiomyopathic myocytes
      in culture.

PMID- 7518171
TI  - [Evaluation of sialic acid levels in serum and degree of sialic acid in gamma
      globulin fraction and C-reactive protein in hemodialysed patients].
AB  - Regulation of immunological processes associated with complement system
      activation and immunoglobulin binding depends, among others, on the presence of
      sialic acids. In haemodialysed patients an increase is found of serum sialic acid
      level. The purpose of the work was the determination of sialic acid content in
      gamma-globulins and C-reactive protein, that is in immunologically active
      glycoproteins. The relationship was also studied between the amount of sialic
      acids and the level of immune complexes. After examination of a group of 15
      haemodialysed patients increased degree of sialization of gamma-globulins was
      found, as compared with a control group. However, the degree of sialization of C
      reactive protein in these patients was decreased in relation to the control
      group. The changes observed in sialic acid content in gamma-globulins and C
      reactive protein in haemodialysed patients modify the function and persistence in
      circulation of these glycoproteins which may be one of the causes of
      immunological disturbances in these patients.

PMID- 7518175
TI  - Immuno-gold electron microscopical detection of heat shock protein 60 (hsp60) in
      mitochondria of rat hepatocytes and myocardiocytes.
AB  - We characterize the specificity of a polyclonal antibody against heat shock
      protein 60 (hsp60) and present an application for ultrastructural localization
      studies of this protein. The antibody was obtained from an IgG fraction (AB 121)
      originally raised against the calcium binding protein calsequestrin by
      immunoabsorption on isolated rat liver hsp60. As shown by partial N-terminal
      amino acid sequence analysis of immunoprecipitated proteins AB 121 contained
      reactivities against hsp60, calsequestrin and the glycoprotein fetuin. In rat
      heart AB 121 recognized calsequestrin and hsp60. In human and rat liver the only
      reacting protein was hsp60. In rat erythrocytes the antibody bound to 61 kDa and
      58 kDa isoforms of fetuin. According to published data no amino acid sequence
      homologies nor common motifs are found between calsequestrin, hsp60 and fetuin.
      As the first application the anti-hsp60 antibody was used for immuno-gold
      electron microscopical localization of hsp60: in myocardiocytes and hepatocytes
      of the rat strong labelling was obtained exclusively in mitochondria. No
      extramitochondrial structures were labelled. The specificity of the antibody and
      its ability to be visualized by immuno-gold electron microscopy offers the
      possibility to study the expression of this protein in the liver and in other
      organs. Possible clinical applications of these studies are discussed, since
      hsp60 could be a target antigen of autoantibodies in diseases such as autoimmune
      hepatitis, primary sclerosing cholangitis or primary biliary cirrhosis.

PMID- 7518176
TI  - Species differences in lectin binding to pulmonary cells: Soybean agglutinin
      (SBA) as a marker of type I alveolar epithelial cells and alveolar macrophages in
      mini pigs.
AB  - We compared lectin staining patterns in rat and mini pig tissues of normal and
      fibrotic (irradiation-induced) lungs. Two lectins were studied: Dolichos biflorus
      (DBA) and Soybean (SBA). Both lectins strongly stained a subpopulation of
      alveolar macrophages. In the rat, DBA positive macrophages were a subpopulation
      of the SBA binding cells. In mini pig lungs, a further specific binding of DBA
      and SBA was observed: DBA reacted with endothelia, and SBA stained the alveolar
      type I cells. Double immunofluorescence experiments using a type II cell-specific
      cytokeratin antibody confirmed the selective reactivity of SBA with type I cells,
      which was also present in fibrotic areas with epithelial cell proliferation.

PMID- 7518177
TI  - Selective fluorescence reaction of indigocarmine stained eosinophil leucocyte
      granules induced by alkaline reduction of the bound dye to its leuco derivative.
AB  - After staining of mammalian blood smears with indigocarmine, eosinophil granules
      were the unique cell components which stained deeply blue under bright field
      illumination. Treatment of stained smears with the reducing agent sodium
      borohydride completely abolished this colour reaction, while under violet-blue
      exciting light eosinophil granules appeared with bright green fluorescence. Other
      reducing agents proved less suitable. Spectral analysis of indigocarmine
      solutions reduced by sodium borohydride showed an emission peak at lambda = 528
      nm and confirmed the microscopic observations. These results indicate that the
      treatment of indigocarmine stained structures with alkaline solutions of strong
      reducing agents converts the bound dye into its reduced and highly fluorescent
      leuco derivative.

PMID- 7518178
TI  - Multiple sclerosis: occurrence of myelin basic protein peptide-reactive T cells
      in healthy family members.
AB  - Genetic factors influence the susceptibility to multiple sclerosis (MS). This
      disease is accompanied by augmented T cell responses to CNS myelin components
      such as myelin basic protein. To evaluate the familial occurrence of such T cell
      autoreactivity, we have studied 12 MS families including 37 healthy first-degree
      relatives for occurrence of numbers of interferon-gamma (IFN-gamma) secreting
      cells among blood mononuclear after culture in presence of myelin basic protein
      (MBP), eight synthetic MBP peptides and the control antigen acetylcholine
      receptor (AChR). There were no differences between MS patients and healthy family
      members regarding frequencies of autoreactive T cells recognizing MBP, the eight
      different MBP peptides or AChR. None of the MBP peptides predominated as T cell
      antigen among the MS patients or their unaffected family members. In some
      families the highest number of MBP peptide reactive T cells were found among
      unaffected family members. No correlation was observed between numbers of MBP or
      MBP peptide reactive T cells in various subjects and their HLA-DR-DQ phenotypes.
      In conclusion, this study has revealed the presence of MBP and MBP peptide
      reactive T cells of similar frequencies in MS patients and their healthy family
      members.

PMID- 7518179
TI  - Bone matrix RGD glycoproteins: immunolocalization and interaction with human
      primary osteoblastic bone cells in vitro.
AB  - The interaction of cells with extracellular matrix is essential for their
      anchorage, proliferation, migration, and differentiation. In bone matrix there
      are multiple glycoproteins that contain the integrin-binding RGD sequence:
      fibronectin (FN), thrombospondin (TSP), osteopontin (OPN), bone sialoprotein
      (BSP), type I collagen (COLL I), and vitronectin (VN). In this study, the
      localization of TSP, FN, VN, and several integrins within developing human long
      bone using immunohistochemical methods was examined, as was the effect of all
      bone RGD proteins on the adhesion of human osteoblastic cells. Thrombospondin,
      fibronectin, and vitronectin showed distinct localization patterns within bone
      tissue. TSP was found mainly in osteoid and the periosteum; VN appeared to be
      present mainly in mature bone matrix. FN was present in the periosteum as well as
      within both mature and immature bone matrix. Using a panel of antiintegrin
      antibodies we found that bone cells in vivo and in vitro express alpha 4, alpha
      v, alpha 5 beta 1, alpha v beta 3, and beta 3/beta 5 integrins, and these
      receptors are for the most part expressed on all bone cells at different stages
      of maturation with quantitative rather than qualitative variations, with the
      exception of alpha 4, which is expressed mainly by osteoblasts. Cell attachment
      assays were performed using primary human cells of the osteoblastic lineage under
      serum-free conditions. COLL I, TSP, VN, FN, OPN, and BSP promoted bone cell
      attachment in a dose-dependent manner and were equivalent in action when used in
      equimolar concentrations. In the presence of GRGDS peptide in the medium, the
      adhesion to BSP, OPN, and VN was almost completely blocked (10, 10, and 15% of
      control, respectively), and attachment to FN, COLL I, and TSP was only slightly
      decreased (80, 75, and 55%, respectively). These results suggest that human bone
      cells may use RGD-independent mechanisms for attachment to the latter
      glycoproteins.

PMID- 7518180
TI  - The role of membrane channels in IgG secretion by plasma cells in the chicken
      lacrimal gland.

PMID- 7518181
TI  - Patterns of cytokeratin expression in impression cytology specimens from normal
      human conjunctival epithelium.

PMID- 7518182
TI  - Tear proteins and enzymes in the chimpanzee.

PMID- 7518183
TI  - Vitronectin in human tears--protection against closed eye induced inflammatory
      damage.

PMID- 7518184
TI  - The tear film: pharmacological approaches and effects.

PMID- 7518185
TI  - A precise method of using rose bengal in the evaluation of dry eye and the
      detection of changes in its severity.

PMID- 7518186
TI  - Amylase in mare lacrimale in patients with submandibular salivary gland
      transplantation to the lacrimal basin.
AB  - Six patients with dry eyes of different etiologies underwent transplants of 1.0
      to 1.6 ml of submandibular salivary gland tissue, five of them to one eye and one
      to both eyes. In the four cases in which the transplants survived, the amylase
      activity in tear fluid sampled from the cisterna lacrimalis (temporal canthal
      meniscus) had a mean value of 5,147 U/l in contrast with the mean value 943 U/l
      of the fellow control eyes. In the two eyes in which the transplants failed to
      survive, the average value was 635 U/l. The small sample size does not enable
      calculation of statistical significance to the results but suggests that salivary
      amylase determinations in tear fluid would facilitate assessment of the
      functional status of the transplanted salivary tissue.

PMID- 7518187
TI  - [Applications of interferon in ophthalmological field and its ocular
      complications].

PMID- 7518188
TI  - [Interferon-induced retinal changes].
AB  - Fifty patients treated with interferon for chronic type C hepatitis, chronic type
      B hepatitis and renal cell carcinoma were examined for retinal complications.
      Retinal hemorrhages or cotton wool spots were observed in 23 (46%) of the
      patients. Retinal hemorrhages without cotton wool spots were found in 14
      patients, cotton wool spots without retinal hemorrhages in 5 patients, and both
      hemorrhages and cotton wool spots in four patients. These findings were
      potentially reversible. There was one case of branch retinal artery occlusion and
      one case with microaneurysm. Red blood cell count decreased significantly in the
      patients with retinopathy compared with those without retinopathy (p < 0.05%).
      Patients with diabetes, hypertension, retinal arterial sclerosis, and anemia were
      at risk for retinopathy.

PMID- 7518189
TI  - Effect of Commiphora molmol (oleo-gum-resin) on the cytological and biochemical
      changes induced by cyclophosphamide in mice.
AB  - The anticlastogenic and biochemical potentials of Commiphora molmol were studied
      in Swiss albino mice treated with cyclophosphamide (CP). The C.molmol treatment
      (125-500 mg/kg) showed no mutagenicity. It caused a highly significant and dose
      dependent mitodepressant effect in the femoral cells and reduction of RNA levels
      in hepatic cells as compared with the control. CP treatment showed significant
      increase in the frequency of micronuclei, cytotoxicity and reduction in the
      contents of nucleic acids and proteins. Pretreatment with C. molmol could neither
      alter the biochemical and cytological effects of CP nor show any additive effect
      of both treatments.

PMID- 7518190
TI  - Fetal membrane rupture is associated with the presence of insulin-like growth
      factor-binding protein-1 in vaginal secretions.
AB  - OBJECTIVE: Our purpose was to determine whether detection of insulin-like growth
      factor-binding protein-1 in vaginal secretions could be used in the diagnosis of
      fetal membrane rupture. STUDY DESIGN: Consenting patients (n = 105) with
      complaints suspicious of membrane rupture between 24 and 42 weeks of gestation
      who had no evidence of placenta previa were enrolled in the study. The diagnosis
      of membrane rupture required at least two of the following findings on vaginal
      examination: pooling of fluid, positive Nitrazine paper (Bristol-Myers Squibb,
      Cherry Hill, N.J.) test, or microscopic evidence of ferning. A swab of the
      posterior vaginal fornix was obtained, placed in sample buffer, and analyzed for
      insulin-like growth factor-binding protein-1 by immunoassay. Data analysis
      included chi 2 analysis, Student t test, or Mann-Whitney U test and linear
      regression and receiver operating characteristic curve analysis. RESULTS: A total
      of 78 (74.3%) patients met the criteria for membrane rupture. There was a highly
      significant difference in mean vaginal insulin-like growth factor-binding protein
      1 concentrations between patients with and without clinical evidence of membrane
      rupture (553.6 +/- 731.4 micrograms/L vs 3.0 +/- 7.3 micrograms/L, p = 0.0002).
      Receiver operating characteristic curve analysis demonstrated that the optimal
      identification of patients with membrane rupture was achieved with an insulin
      like growth factor-binding protein-1 value > 3 micrograms/L (sensitivity 74.4%,
      95% confidence interval 64.7% to 84.0%; specificity 92.6%, 95% confidence
      interval 82.7% to 102.5%; positive predictive value 96.7%, 95% confidence
      interval 92.1% to 101.2%; negative predictive value 55.6%, 95% confidence
      interval 41.0% to 70.1%). CONCLUSIONS: The presence of vaginal insulin-like
      growth factor-binding protein-1 is highly predictive of membrane rupture,
      identifying 74.4% of affected patients with a very low false-positive rate.

PMID- 7518191
TI  - Myofibroblasts and their role in lung collagen gene expression during pulmonary
      fibrosis. A combined immunohistochemical and in situ hybridization study.
AB  - Appearance of contractile filament-laden stromal cells or myofibroblasts is a
      characteristic of lung fibrotic lesions. The role of these cells in fibrosis and
      their cytoskeletal phenotype are not fully delineated. This study was undertaken
      to further investigate these issues using a model of lung fibrosis. Rats were
      treated endotracheally with bleomycin on day 0, and their lungs examined at
      various time points by in situ hybridization for alpha 1(I) procollagen mRNA
      expression and by immunohistochemistry for desmin and alpha-smooth muscle actin
      expression. The results show an increase in the number of cells resembling
      fibroblasts and strongly positive for alpha-smooth muscle actin, desmin and
      procollagen mRNA expression in lungs of animals treated with bleomycin, with the
      increase being maximal between days 7 and 14 after bleomycin treatment. Two types
      of newly positive cells could be discerned. The first expressing alpha-smooth
      muscle actin, desmin, and procollagen mRNA was localized in active fibrotic
      lesions. The second expressing only alpha-smooth muscle actin and procollagen
      mRNA was localized in fibrotic submesothelial areas. Almost all of the newly
      reactive alpha-smooth muscle actin-positive cells strongly express procollagen
      mRNA, and they constituted most of the cells actively expressing procollagen.
      These findings suggest that the newly appearing myofibroblast characterized by
      alpha-smooth muscle actin and/or desmin expression may be responsible for most if
      not all of the increased lung collagen gene expression in pulmonary fibrosis.

PMID- 7518192
TI  - Polyinosinic:polycytidylic acid is a potent activator of endothelial cells.
AB  - Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded
      polyribonucleotide that elicits immune responses analogous to those observed
      during viral infection. It is also known to modulate the expression of certain
      autoimmune disorders including diabetes mellitus in the BB rat and NOD mouse. The
      mechanism underlying these immunomodulatory effects is not known, but it could
      involve activation of vascular endothelium. We now report that parenteral poly
      I:C induces rat pancreatic endothelium to hyperexpress intercellular adhesion
      molecule 1 (CD54). This is accompanied by a perivascular recruitment of
      mononuclear cells to the exocrine pancreas. Corollary in vitro studies
      demonstrated that poly I:C is a potent activator of both rat and human
      endothelial cells in culture. It upregulates endothelial expression of several
      leukocyte adhesion molecules, stimulates the release of interleukin-6 and
      interleukin-8, and antagonizes interferon-gamma induction of major
      histocompatibility complex class II expression. We conclude that poly I:C
      activates endothelial cells to express surface molecules and cytokines in a
      pattern classically associated with leukocyte recruitment. These effects may in
      part contribute to the immunomodulatory effects of poly I:C in animal models of
      autoimmunity.

PMID- 7518195
TI  - Absence of HLA class I expression by Reed-Sternberg cells.
AB  - The reactive cell population in Hodgkin's disease consists of predominantly CD4+
      helper T cells and lacks CD8+ cytotoxic T cells and natural killer cells. This
      lack of a CD8+ response is surprising in view of the expression of the latent
      Epstein-Barr viral protein LMP by Reed-Sternberg cells in many cases of Hodgkin's
      disease, Deficient HLA class I expression would be one possible mechanism to
      avoid a CD8+ cytotoxic immune response. To test this possibility we studied the
      expression of HLA class I and II determinants on Reed-Sternberg cells in tissue
      sections and cell suspensions of Hodgkin's disease. Frozen tissue sections of 40
      cases and cytocentrifuge preparations from cell suspensions of 10 lymph nodes
      involved by Hodgkin's disease were studied with monoclonal antibodies reactive
      with HLA determinants. As a control frozen tissue sections of two cases of
      infectious mononucleosis were studied. Careful examination of the tissue sections
      and subsequently of cytospins of cell suspensions showed that the Reed-Sternberg
      cells frequently lacked HLA class I but showed strong staining for HLA class II.
      Absence of HLA class I expression on Reed-Sternberg cells and their variants
      provides an explanation for the lack of a CD8+ cytotoxic immune response against
      antigens expressed on Reed-Sternberg cells.

PMID- 7518194
TI  - Evidence for involvement of ICAM-1 and VCAM-1 in lymphocyte interaction with
      endothelium in experimental autoimmune encephalomyelitis in the central nervous
      system in the SJL/J mouse.
AB  - We have investigated the expression of vascular adhesion molecules during the
      first stage of chronic inflammation in experimental autoimmune encephalomyelitis
      in the SJL/J mouse. Immunocytochemical analysis of frozen sections of inflamed
      versus noninflamed brains and spinal cords showed that the vascular endothelium
      in brains and spinal cords from diseased animals expressed high levels of
      vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1
      (ICAM-1) but no detectable mucosal addressin or peripheral lymph node addressin.
      In frozen section assays, anti-alpha 4 integrin and anti-VCAM-1 monoclonal
      antibodies inhibited binding of mouse peripheral lymphocytes to inflamed brains
      at both 4 C and 20 C. Antilymphocyte function-associated antigen-1 and anti-ICAM
      1 monoclonal antibodies inhibited binding of mouse peripheral lymphocytes to
      inflamed brains at 20 C. These results are consistent with an important role for
      the vascular adhesion molecules VCAM-1 and ICAM-1 and for their lymphocytes
      receptors in lymphocyte recruitment to the central nervous system.

PMID- 7518197
TI  - Smooth-muscle proliferation in dermatofibromas.
AB  - Although a variety of epithelial changes have been associated with
      dermatofibromas, mesenchymal proliferations induced by dermatofibromas appear to
      be rare. We report three dermatofibromas that were associated with proliferation
      of smooth muscle within the adjacent dermis. The lesions ranged from a large,
      densely cellular dermatofibroma with "monster cells" to a sparsely cellular,
      fibrous lesion. In all three cases, the smooth muscle could be discerned in
      hematoxylin- and -eosin-stained sections, because its presence caused an
      interruption in the pattern of reticular dermal collagen bundles with blunt-ended
      vesicular nuclei. Well-formed fascicles were apparent in immunoperoxidase-stained
      sections using antisera to muscle-specific actin (HHF-35) and desmin. The smooth
      muscle failed to stain with either antisera to S-100 protein or Leu-7, precluding
      determination of whether it immunophenotypically resembled vascular or pilar
      smooth muscle. We believe that the smooth-muscle proliferation in our cases was
      induced by the spindled cells of dermatofibroma, just as epithelial changes in
      association with dermatofibroma are. We further believe that it is most likely of
      vascular derivation, based on a previous report of angioleiomyoma arising in a
      dermatofibroma as well as the continuity of fascicles of smooth muscle with a
      thick-walled vessel in one of our cases. Less likely explanations include
      collisions between dermatofibromas and leiomyomas or divergent differentiation in
      a proliferation arising from primitive mesenchymal cells.

PMID- 7518193
TI  - Microtubule-associated protein tau epitopes are present in fiber lesions in
      diverse muscle disorders.
AB  - The microtubule-associated protein tau is a major cytoskeletal protein involved
      in the neurofibrillary tangles of Alzheimer's disease. Although tau is
      predominantly a neuronal protein, it has been demonstrated in glia and other
      nonneuronal cells. We describe the presence of microtubule-associated protein tau
      epitopes in various muscle fiber lesions in oculopharyngeal and Becker muscular
      dystrophy, dermatomyositis, central core disease, neurogenic atrophy, and in the
      recovery phase of an attack of malignant hyperthermia. Western blot demonstrated
      a 100- to 110-kd tau-immunoreactive protein probably corresponding to 'big tau'
      as described in peripheral nerves. Tau immunoreactivity in muscle fiber lesions
      usually co-localized with tubulin, although electron microscopy failed to show an
      increase in microtubules. Tau and tubulin reactivity also correlated with the
      presence of desmin and vimentin epitopes. Possible explanations for the presence
      of tau are briefly discussed.

PMID- 7518196
TI  - Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and
      reactive hyperplasia.
AB  - Mantle cell (centrocytic) lymphoma (MCL) and occasional cases of B-cell small
      lymphocytic lymphoma/chronic lymphocytic leukemia (B-SLL/CLL) show a
      characteristic translocation, t(11:14)(q13;q32) involving rearrangement of the
      Bcl-1 region. Recently it was shown that the key Bcl-1 region oncogene is cyclin
      D1/PRAD1; cyclin D1 mRNA was shown to be overexpressed in cases of MCL. We
      examined cyclin D1 protein expression in low-grade B-cell lymphomas and reactive
      lymphoid hyperplasias using polyclonal and monoclonal antibodies to cyclin D1
      protein. Definite nuclear staining was seen in 15 of 15 MCLs, 1 of 7 B-SLL/CLLs,
      0 of 7 reactive hyperplasias, 0 of 10 follicular lymphomas, and 0 of 4 lymphomas
      of mucosa-associated lymphoid tissue using immunoperoxidase stains on paraffin
      embedded sections. Best results were obtained with the affinity-purified
      polyclonal antibody on microwave-treated, formalin-fixed, paraffin-embedded
      tissue. MCLs showed diffuse nuclear staining, whereas the one positive B-SLL/CLL
      showed dot-like or globular nuclear staining. Nuclear cyclin D1 protein can be
      detected in all cases of MCL and in rare cases of B-SLL/CLL using an
      immunohistochemical technique on formalin-fixed, paraffin-embedded tissue, and it
      does not appear to be detectable in reactive hyperplasias and other low-grade B
      cell lymphomas. This protein may be useful in subclassification of low-grade B
      cell lymphomas.

PMID- 7518199
TI  - Apparent retardation of aging in Drosophila melanogaster by inhibitors of reverse
      transcriptase.
AB  - It is proposed that aging is induced by somatic replication of transposable
      elements (TEs). Most transposable elements in Drosophila reproduce by reverse
      transcription. Therefore inhibitors of reverse transcriptase were tested for
      their ability to retard aging in Drosophila melanogaster. Two inhibitors,
      phosphonoformic acid (PFA) and dideoxyinosine (ddI), were capable of prolonging
      life span when administered for the first half of the adult life. PFA was
      investigated further. It also produced a reduction in the rate of decline of
      behavior. PFA appeared not to act on an infectious agent in these experiments,
      nor did it alter the food intake. Analogues unable to inhibit RT had no life span
      prolonging effect at similar concentrations to that of PFA.

PMID- 7518200
TI  - Restorative effect of Bacillus subtilis spores on interferon production in aged
      mice.

PMID- 7518198
TI  - Mitochondrial DNA transcription and translation in aged rat. Effect of acetyl-L
      carnitine.

PMID- 7518202
TI  - VIP enhances and nitric oxide synthase inhibitor reduces survival of rat lungs
      perfused ex vivo.
AB  - VIP delayed the onset of edematous lung injury in isolated perfused rat lungs by
      64%, and was more effective than PGI2 in prolonging lung survival ex vivo. While
      PGI2 increased survival by 37 min versus Krebs/BSA only, VIP increased it by 2 h
      and 17 min. On the other hand, inhibition of NO. synthase, which protected the
      lung against oxidant injury caused by paraquat or X/XO,3 actually hastened the
      onset of injury caused by prolonged perfusion ex vivo, suggesting opposite roles
      for NO. in different forms of oxidant injury.

PMID- 7518201
TI  - Cytokines, neuropeptides, and reperfusion injury during magnesium deficiency.
AB  - In summary, hypomagnesemia enhances reperfusion injury. We postulate that
      neurogenic inflammation, which occurs very early during hypomagnesemia,
      predisposes the myocardium to reperfusion injury by depleting endogenous
      antioxidants and recruiting inflammatory cells, which can participate in enhanced
      free radical production during postischemic reperfusion. Vitamin E supplements
      can prevent the occurrence of this enhanced injury possibly through the
      restoration of endogenous antioxidant defenses.

PMID- 7518203
TI  - Nitric oxide: a potent mediator of glutamatergic neurotoxicity in brain ischemia.

PMID- 7518204
TI  - The effect of immunosuppressants on human leukocyte NADPH oxidase.

PMID- 7518206
TI  - Are CNS lesions produced by free radicals?

PMID- 7518205
TI  - A putative new retrovirus associated with multiple sclerosis and the possible
      involvement of Epstein-Barr virus in this disease.
AB  - Since tropical spastic paraparesis in 1985 was found to be associated with HTLV-I
      infection, it has been suggested that a retrovirus might be involved in multiple
      sclerosis (MS). Our group has studied long-term cultures of cerebrospinal fluid
      cells and peripheral blood mononuclear cells from MS patients and controls with
      the purpose of elucidating the possible involvement of a retrovirus in MS. For an
      extended period electron microscopical analysis (EM) of T-cell lines, derived
      from MS patients and controls and cultured for 4 weeks was performed. In two
      cultures obtained 8 months apart from a patient with progressive MS, retrovirus
      like particles were observed in 1-2% of the cells examined. Recently a B
      lymphoblastoid cell line (LCL) producing retrovirus-like particles and EBV was
      established from a 30-year-old male patient with a chronic progressive
      myelopathy, clinically resembling multiple sclerosis. Similar cell lines have now
      been established from two MS patients. The retrovirus-like particles produced by
      the LCL have been purified by gradient ultracentrifugation. In the purified
      material reverse transcriptase assays are clearly positive in the gradients where
      EM shows retrovirus-like particles. Antigen characterization, nucleic acid
      sequence analysis and antibody studies are now being performed. The retrovirus
      found is definitively different from other known human retroviruses. It has
      previously been found that 100% of patients with MS have antibodies against EBV,
      in contrast to controls where only 86-95% have antibodies against this virus.
      Previous epidemiological studies have pointed toward a post-pubertal primary EBV
      infection as an important event in the induction of MS disease. These studies
      have now been substantiated by our group. Though it is still unknown whether EBV
      infection is a prerequisite for development of MS or whether the 100% EBV
      seropositivity is a consequence of the MS disease, we have put forward the
      hypothesis that the etiological agent for development of MS and MS-like diseases
      is a new hitherto uncharacterized retrovirus, whereas development of neurologic
      disease is related to or even dependent on a delayed infection with a virus from
      the herpes group, most likely EBV. This dual infection hypothesis has been
      analyzed and was found to be in accordance with the most consistent
      epidemiological characteristics of MS. We have previously, also from
      epidemiological data, negated retroviruses, behaving as the known human
      retroviruses, as an independent cause of MS.

PMID- 7518207
TI  - New developments in the chemotherapy of lentivirus (human immunodeficiency virus)
      infections: sensitivity/resistance of HIV-1 to non-nucleoside HIV-1-specific
      inhibitors.
AB  - Of the different steps of the HIV replicative cycle, the reverse transcription
      step has received most attention as a target for chemotherapeutic intervention.
      The reverse transcriptase (RT) can be blocked by both nucleoside (nucleotide) and
      non-nucleoside type of inhibitors. Whereas the former act as competitive
      inhibitors with respect to the natural substrates or alternate substrates (chain
      terminators), the latter act allosterically with a non-substrate binding site of
      the enzyme. Several non-nucleoside types of RT inhibitors have proved to inhibit
      HIV-1 replication at nanomolar concentrations that are 10(4)- to 10(5)-fold lower
      than the cytotoxic concentrations. Although a non-nucleoside HIV-1-specific RT
      inhibitor may rapidly select for virus-drug resistance in cell culture, the
      resulting mutant strain may or may not show cross-resistance, and in some
      instances even hypersensitivity, to other HIV-specific RT inhibitors. When used
      at the appropriate concentrations, HIV-1-specific RT inhibitors are able to
      completely shut off ("knock-out") virus replication in vitro, under conditions
      where dideoxynucleoside analogues such as AZT fail to do so. This apparent
      "sterilizing effect" achieved by the non-nucleoside type of HIV-1-specific RT
      inhibitors opens new perspectives for the treatment of HIV infections in
      patients.

PMID- 7518208
TI  - The value of studying the cerebrospinal fluid in slow viral and related diseases.

PMID- 7518209
TI  - Increased expression of ELAM-1, ICAM-1, and VCAM-1 on bronchial biopsies from
      allergic asthmatic patients.

PMID- 7518210
TI  - Endotoxin-induced neutrophil adherence to endothelium: relationship to CD11b/CD18
      and L-selectin expression and matrix disruption.
AB  - The injury to vascular endothelium seen in severe bacterial infection may be
      mediated by neutrophil-derived enzymes. Neutrophil adhesion to endothelium, a
      prerequisite for this process, is mediated sequentially by the leukocyte adhesion
      molecules L-selectin and the beta 2 integrins, including CD11b/CD18. We have
      explored the relationship between expression of these molecules, neutrophil
      adherence, endothelial activation, and consequent endothelial injury, as assessed
      in vitro by changes to HS and FN matrices that colocalize. Endothelial
      prestimulation with LPS (endotoxin) caused an increase in adherence and an
      inversely proportional disruption in the HS matrix; disruption of the FN matrix
      only occurred on the further addition of fMLP. Although maximal changes in these
      matrices were associated with elevation of neutrophil CD11b/CD18 and reduction in
      L-selectin expression, these changes did not determine either the nature or
      extent of endothelial damage. CD11b/CD18 expression was similar in both adherent
      and nonadherent neutrophils, while L-selectin was shed in association with
      adherence in the absence of other stimuli. These changes in expression were thus
      independently regulated. This model may provide further insights into the
      interrelationship between neutrophil adhesion and activation and endothelial
      damage in infection with gram-negative bacteria.

PMID- 7518211
TI  - Molecular control of B-cell immunopoiesis.

PMID- 7518212
TI  - Modulation by rm interferon-gamma and CD4+ T-lymphocytes of allergic eosinophil
      accumulation in the mice peritoneal cavity.

PMID- 7518213
TI  - Differentiation of human mast cells from bone-marrow and cord-blood progenitor
      cells by factors produced by a mouse stromal cell line.
AB  - Human bone-marrow or cord-blood progenitors (i.e., CD34+ cells) are easily
      purified by immunological methods and can be cultured on normal human-bone-marrow
      stromal cells for limited periods of time. Under these culture conditions, the
      number of progenitors declines in a few weeks and these cells disappear
      completely in less than 8 weeks. This fact suggests that this culture system is
      deprived of growth factor(s) able to support the self-renewal of stem cells. We
      have developed the culture of immunomagnetically purified human-bone-marrow- or
      cord-blood-derived CD34+ cells on a supportive mouse lipoblastic stromal cell
      line, MS-5. The long-term survival of clonogenic cells was analyzed in these
      cultures and compared with the results obtained by culture on human-bone-marrow
      stromal cells. The results demonstrated that only coculture of CD34+ cells on MS
      5 layers allows the survival of clonogenic progenitors for at least 12 weeks.
      Cytospin smears were regularly performed and cell morphology was examined after
      classical staining methods (i.e., M.G.G. and toluidine blue staining). Histologic
      analysis demonstrated the growth of mast-cell-like metachromatic cells after the
      second week of incubation on MS-5 layer. The highest percentage of these cells
      was observed after 8 weeks, and averaged about 30 percent for cord-blood cells
      and 70 percent for bone-marrow cells. To further confirm the nature of the
      metachromatic cells obtained under this culture condition, immunohistochemical
      staining of tryptase was performed on the same samples. The results demonstrated
      similar percentages of tryptase+ cells and of metachromatic elements. Measurement
      of cellular histamine demonstrated that culture of CD34+ cells on MS-5 monolayers
      induced the formation and increase of this mediator. To determine whether the
      contact between MS-5 layers and CD34+ cells was an absolute requirement for the
      development of mast cells, CD34+ cells were cultured in the presence of MS-5
      conditioned medium. This condition allowed the development of similar percentage
      of mast cells when compared with the coculture experiments, indicating that a
      soluble factor was involved in mast cell differentiation. Whatever the soluble
      factor(s) responsible for this mast cell growth activity, our culture system
      allows us to obtain significant amounts of highly enriched normal human mast cell
      populations useful for further studies on the reactivity of this cell subset.

PMID- 7518214
TI  - Growth and colony-stimulating factors mediate eosinophil fibroblast interactions
      in chronic airway inflammation.

PMID- 7518215
TI  - RANTES, a novel eosinophil-chemotactic cytokine.

PMID- 7518216
TI  - Preclinical evaluation of MKC-442, a highly potent and specific inhibitor of
      human immunodeficiency virus type 1 in vitro.
AB  - MKC-442 (6-benzyl-1-ethoxymethyl-5-isopropyluracil or I-EBU) has recently been
      identified as a highly potent and specific inhibitor of human immunodeficiency
      virus type 1 (HIV-1) reverse transcriptase. Since the compound has favorable
      pharmacokinetic and toxicity profiles in vivo, we have evaluated MKC-442 for its
      inhibitory effect on the replication of HIV-1 in various cell cultures, including
      human peripheral blood lymphocytes and monocyte-macrophages. The 50 and 90%
      effective concentrations for HIV-1 (HTLV-IIIB strain) replication in MT-4 cells
      were 15 and 98 nM, respectively. MKC-442 was also inhibitory to HIV-1 replication
      in peripheral blood lymphocytes and monocyte-macrophages as determined by the
      production of p24 antigens in the culture supernatant. Fluorescence-activated
      cell sorter analysis revealed that MKC-442 was equally active against zidovudine
      resistant mutants and zidovudine-susceptible strains. Furthermore, combinations
      of MKC-442 with either 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, or
      2',3'-dideoxyinosine synergistically inhibited the replication of HIV-1. Thus,
      MKC-442 has been considered as a candidate for clinical efficacy studies.

PMID- 7518217
TI  - Effect of oxetanocin G, a novel nucleoside analog, on DNA synthesis by hepatitis
      B virus virions.
AB  - The novel nucleoside oxetanocin G, 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro
      oxetanosyl)guanine (OXT-G), that is a derivative of oxetanocin A, was studied in
      relation to its action on the synthesis of hepatitis B virus (HBV) DNA and
      cellular DNA in an HBV-producing cell line, HB611 (T. Tsurimoto, A. Fujiyama, and
      K. Matsubara, Proc. Natl. Acad. Sci. USA 84:444-448, 1987). The median effective
      concentration of OXT-G against HBV replication was 1.5 microM, and the median
      cytotoxic concentration was more than 1,000 microM. At the same concentration,
      OXT-G did not inhibit cellular DNA synthesis or viral RNA synthesis. Chemically
      synthesized OXT-GTP inhibited the HBV endogenous DNA polymerase reaction and was
      incorporated into HBV DNA strands at a low efficiency compared with the
      incorporation of dGTP. A synthetic primer-template study revealed that OXT-GTP
      was incorporated into DNA strands at a low efficiency and that further extension
      of the DNA strand by using the 2' position of the incorporated OXT-G could take
      place.

PMID- 7518219
TI  - Phylogenetic analysis of the hyperthermophilic pink filament community in Octopus
      Spring, Yellowstone National Park.
AB  - The phylogenetic diversity of a well-known pink filament community associated
      with the 84 to 88 degrees C outflow from Octopus Spring, Yellowstone National
      Park, was examined. Three phylogenetic types ("phylotypes"), designated EM 3, EM
      17, and EM 19, were identified by cloning and sequencing the small subunit rRNA
      genes (16S rDNA) obtained by PCR amplification of mixed-population DNA. All three
      phylotypes diverge deeply within the phylogenetic domain Bacteria sensu Woese (C.
      R. Woese, O. Kandler, and M. L. Wheelis, Proc. Natl. Acad. Sci. USA 87:4576-4579,
      1990). No members of the Archaea or Eucarya were detected. EM 3 comprises a
      unique lineage within the Thermotogales group, and EM 17 and EM 19 are affiliated
      with the Aquificales. A total of 35 clones were examined, of which the majority
      (26 clones) were of a single sequence type (EM 17) closely related to Aquifex
      pyrophilus. In situ hybridization with clone-specific probes attributes the
      majority sequence, EM 17, to the pink filaments.

PMID- 7518220
TI  - Role of vascular nitric oxide synthase in endotoxin shock of Propionibacterium
      acnes-sensitized rats.
AB  - The sensitivity of animals to endotoxin differs significantly between species.
      Thus, factors that determine the susceptibility to endotoxin may play important
      roles in the pathogenesis of septic shock. In order to determine the mechanism
      responsible for susceptibility to endotoxin, the effect of lipopolysaccharide
      (LPS) on the circulatory status of Propionibacterium acnes (PA)-sensitized rats
      was studied. Following the intravenous administration of a low dose of LPS, the
      arterial blood pressure of PA-treated rats, but not of normal animals,
      progressively decreased; the PA-sensitized animals died of circulatory shock
      within 7 h of LPS administration. N omega-nitro-L-arginine (NA) reduced the
      depressor effect of LPS by an L-arginine-inhibitable mechanism. Administration of
      LPS markedly increased the level of the inducible type of nitric oxide (NO)
      synthase in various tissues, including the aorta, of PA-treated rats but not of
      control animals. LPS also increased plasma levels of nitrate plus nitrite and
      aortic levels of cGMP. Dexamethasone inhibited the de novo synthesis of NO
      synthase in the aorta and other tissues and reduced the depressor effect of LPS.
      These and other findings suggest that induction of nitric oxide synthase in
      resistant arteries might underlie the pathogenesis of LPS-induced hypotension in
      PA-sensitized animals and the mechanism responsible for the susceptibility to
      endotoxin.

PMID- 7518218
TI  - Influence of stereochemistry on antiviral activities and resistance profiles of
      dideoxycytidine nucleosides.
AB  - beta-L-2',3'-Dideoxycytidine (beta-L-ddC) and beta-L-5-fluoro-2',3'
      dideoxycytidine (5-F-beta-L-ddC) were prepared and shown to have potent activity
      against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV).
      These compounds were compared with beta-D-2',3'-dideoxycytidine (beta-D-ddC) and
      two beta-L-oxathiolane nucleosides (beta-L-3'-thio-2',3'-dideoxycytidine and beta
      L-5-fluoro-3'-thio-2',3'-dideoxycytidine) in terms of anti-HIV and anti-HBV
      activity, cytotoxicity, and development of HIV-1 resistance. Compared with beta-D
      ddC, the beta-L-dideoxycytidine nucleosides had similar anti-HIV-1 activities,
      significantly greater anti-HBV activities, and decreased toxicities to a B-cell
      line, T-cell lines, and human bone marrow progenitor cells. HIV-1 strains
      resistant to beta-D-ddC were susceptible to the beta-L-ddC analogs. Compared with
      the beta-L-oxathiolane nucleosides, beta-L-ddC and 5-F-beta-L-ddC had similar
      anti-HIV-1 activities, decreased anti-HBV activities, and greater toxicities to B
      and T-cell lines and bone marrow progenitor cells. There were similarities
      between the beta-L-ddC and beta-L-oxathiolane nucleosides in the rate of
      development and pattern of resistant HIV-1 selection. While the in vitro activity
      and cytotoxicity profiles of the beta-L-ddC nucleosides differed from those of
      the beta-D-ddC and beta-L-oxathiolane nucleosides, the data presented herein
      suggest that the sugar configuration of a dideoxynucleoside analog may play a
      major role in the rate of development and the pattern of HIV-1 resistance.

PMID- 7518222
TI  - [Clinical significance of angiogenesis in gastric carcinoma as a predictive
      marker for recurrence].

PMID- 7518221
TI  - Mechanism of prostaglandin E2 release and increase in PGH2/PGE2 isomerase
      activity by PDGF: involvement of nitric oxide.
AB  - We examined the possibility that the platelet-derived growth factor-induced
      release of prostaglandin E2 and increase in prostaglandin H2 (PGH2)/prostaglandin
      E2 (PGE2) isomerase activity (EC 5.3.99.3) in NIH3T3 cells was mediated by nitric
      oxide. Addition of L-NG-nitroarginine methyl ester or diphenyleneiodonium
      chloride, potent nitric oxide synthase inhibitors, blocks platelet derived growth
      factor-induced release of prostaglandin E2, lowers basal prostaglandin E2
      release, and also blocks the growth factor-induced increase in PGH2/PGE2
      isomerase activity. Exogenous nitric oxide stimulates prostaglandin E2 release in
      NIH3T3 cells and this stimulation is blocked by hemoglobin. In contrast,
      exogenous nitric oxide failed to induce prostaglandin E2 release from pEJ/ras
      transformed cells. The nitric oxide induction of PGH2/PGE2 isomerase activity and
      prostaglandin E2 release occurred within minutes in contrast to alterations in
      prostaglandin H synthase/cyclooxygenase. These findings link three different
      classes of messenger molecules (growth factors, nitric oxide, prostaglandins).

PMID- 7518223
TI  - Hospital admissions for asthma in preschool children: relationship to major roads
      in Birmingham, United Kingdom.
AB  - This study examined the relationship between residence near major roads, traffic
      flow, and risk of hospital admission for asthma in children younger than 5 y of
      age living in Birmingham, United Kingdom. Area of residence and traffic flow
      patterns were compared for children admitted to the hospital for asthma, children
      admitted for nonrespiratory reasons, and a random sample of children from the
      community. Children admitted with an asthma diagnosis were significantly more
      likely to live in an area with high traffic flow (> 24,000 vehicles/24 h) located
      along the nearest segment of main road than were children admitted for
      nonrespiratory reasons (p < .02) or children from the community (p < .002). A
      significant linear trend was observed for traffic flow (p < .006) for children
      living less than 500 m from a main road but not for those living farther away.
      Children admitted for nonrespiratory reasons were more likely to be admitted than
      children in the community sample if they lived within 200 m of a main road (p <
      .02), irrespective of traffic flow.

PMID- 7518224
TI  - Intracellular processing and antigenic maturation of measles virus hemagglutinin
      protein.
AB  - The intracellular processing and antigenic maturation of the measles virus (MV)
      hemagglutinin (H) protein in virus infected cells were probed with murine
      monoclonal antibodies (Mabs) that reacted with continuous and discontinuous
      epitopes. The antibodies distinguished between the immature, cotranslational
      monomeric form of the protein and the mature, dimeric hemagglutinin structure.
      This was evidenced by testing of immunoreactivity of the Mabs with synthetic
      peptides, by in vitro synthesized H protein analysis, and by pulse-chase analysis
      of gel separated monomeric and dimeric forms of the H protein. Time kinetics
      analysis showed that the protein was synthesized as monomers and most of them
      were converted into dimers with t1/2 about 30 min. The H protein remained
      endoglycosidase H (Endo H) sensitive up to 30 min and started to acquire partial
      resistance to Endo H between 30 and 60 min (t1/2 about 60 min) after synthesis.
      Oligomerization of the H protein was unaffected in virus infected cells treated
      with a compound (carbonylcyanide m-chlorophenylhydrazone, CCCP) that blocks
      transport from the endoplasmic reticulum (ER) to the Golgi complex. These results
      suggest that the H protein dimerization takes place in the ER before its
      transport to the medial Golgi complex. The Mabs specific for discontinuous
      epitopes reacted with the H protein in cells treated with CCCP. Thus
      conformational antigenic epitope formation appears to take place in the ER.

PMID- 7518227
TI  - [Clinical evaluation of whole blood histamine release test simultaneously testing
      multiple allergens--correlated with bronchial provocation test].
AB  - We compared the efficacy of the novel histamine release test (HRT), which allows
      the determination of many allergens at the same time using a small amount of
      whole blood, with other conventional allergen diagnostic tests. HRT and RAST were
      both performed along with bronchial provocation tests (BPT) on 44 bronchial
      asthma patients in whom the etiologic allergen could not be determined by either
      intracutaneous tests (ICT) or ophthalmic response tests (ORT). The HRT uses a
      microtiterplate on which glass fibers have 10 kinds of allergens affixed. The
      histamine release ability at 6 different concentrations of each kind of allergen
      was examined. The concordance of HRT with respect to BPT was the highest at 82%
      in comparison with RAST at 66%, ICT at 55% and ORT at 60%. With each of the
      allergens, HRT had the highest concordance with BPT. On the other hand, RAST, ICT
      and ORT showed different results depending on the allergens. The positive
      predictive value of HRT was the highest at 76% compared with RAST at 59%, ICT at
      51% and ORT at 64%. From these results, we concluded that HRT is a more useful
      diagnostic method for the confirmation of a clinical allergy than other
      conventional diagnostic methods.

PMID- 7518225
TI  - Comparative immunological characterization of type-specific and conserved B-cell
      epitopes of pinniped, felid and canid herpesviruses.
AB  - Murine monoclonal antibodies (MAbs) were generated against phocid herpesviruses
      (PhHV 2557/Han88 and 7848/Han90) isolated from European harbour seals (Phoca
      vitulina), and against strains of both felid (FHV strain FVR 605) and canid
      herpesviruses (CHV isolate 5105/Han89). MAbs were characterized with respect to
      certain biological properties and used to outline antigenicity profiles of
      isolates of PhHV (n = 8), FHV (n = 7) and CHV (n = 3) in enzyme immunoassays
      employing fixed infected cells. A close antigenic relationship between
      herpesviruses derived from pinnipeds and terrestrial carnivores became evident:
      The majority of the MAbs was directed against epitopes which were expressed by at
      least two of the viral species tested. A number of MAbs detected epitopes which
      were conserved between all isolates of PhHV, FHV and CHV. A few MAbs recognized
      type-specific B-cell epitopes and facilitated the identification of single viral
      species. Moreover, the PhHV isolate 7848/Han90 was antigenically distinguishable
      both from seven other phocid herpesvirus isolates and from FHV or CHV. PhHV
      7848/Han90 proved to be antigenically distinct from all other viruses tested when
      examined by cross neutralization utilizing various reconvalescent and hyperimmune
      sera. Although more data are needed to ensure that PhHV 7848/Han90 indeed is a
      new genuine seal herpesvirus, the preliminary clustering of two groups of phocid
      herpesvirus isolates, tentatively designated PhHV-1 (type isolate 2557/Han88) and
      PhHV-2 (represented by 7848/Han90), seems to be justified. By using selected MAbs
      an unambiguous identification and typing of herpesvirus isolates derived from
      marine mammals and terrestrial carnivores is significantly facilitated.

PMID- 7518228
TI  - [Diagnostic value of glass microfibre-based basophil histamine release test in
      food allergic children. Comparison with specific IgE antibody and skin scratch
      test].
AB  - We evaluated the diagnostic value of the glass microfibre-based histamine release
      test (HRT), which allows measurements to be performed using small amounts of
      whole blood, in 50 children with food allergy case histories. The patients were
      evaluated by radioallergosorbent tests (RAST), skin scratch tests (ST) and food
      challenge tests. Of the 50 patients, 39 had a confirmed clinical diagnosis of
      food allergy from food challenge tests and case histories, and were affected by a
      total of 60 positive allergens (egg 37, milk 11, soy beans 4, wheat 5, rice 3).
      The concordance, sensitivity, and specificity of HRT with the clinical diagnosis
      were 85.3%, 66.7% and 92.1%, those of RAST were 59.4%, 90.0% and 48.2%, and those
      of ST were 84.7%, 71.8% and 88.7%, respectively. The positive predictive values
      of HRT, RAST and ST were 75.5%, 38.8% and 66.7%. The false positive ratio of HRT
      (24.5%) was the lowest among all the tests. There was a significant correlation
      between HRT and RAST (r = 0.513, p < 0.001). However, the concordance of HRT with
      respect to RAST was 56.0%. The concordance and specificity of HRT in relation to
      the clinical diagnosis were higher than RAST and the same as ST. The sensitivity
      of RAST was higher than that of HRT. From these results, we concluded that RAST
      is good for the screening of allergens and that HRT is a useful diagnostic method
      for the confirmation of a clinical allergy.

PMID- 7518226
TI  - The major species specific epitope in prion proteins of ruminants.
AB  - The species specific nature of an antigenic determinant previously discovered in
      the scrapie form of prion protein (PrPD) from cattle, sheep and mice, was further
      investigated in normal prion protein (PrPC) from these and other species. This
      was carried out with eight different anti-peptide sera raised in rabbits against
      various synthetic peptides representing segments of the amino acid (aa) sequence
      101-122 of ovine, bovine, murine and hamster PrP. Antipeptide serum against a
      peptide representing aa 107-122 of ovine PrP showed almost specific reaction and
      crossreacted in immunoblot with caprine and human PrP only. Antisera to the
      corresponding bovine sequence stained bovine and porcine PrP and to a minor
      extent PrP of goat, man, cat, and mink, while antiserum to the murine aa sequence
      reacted with rodent and monkey PrP only. In contrast, antiserum to the
      corresponding hamster sequence displayed a broader reactivity pattern, just like
      the four other anti-peptide sera to various ovine and bovine sequences. Antisera
      were also tested for reactivity with the pathogenic isoforms of PrP of sheep,
      cow, hamster and mouse and showed generally similar reactivity patterns as by
      using PrPC. In conclusion, the region close to the actual or putative proteinase
      K cleavage sites of PrP seems to exhibit high structural variability among
      mammalian species.

PMID- 7518229
TI  - [Changes in histamine levels in skin chambers. Application for clinical
      evaluation of atopic dermatitis--report 2].
AB  - We measured changes in histamine levels in fluids from children with moderate or
      severe atopic dermatitis by the skin chamber method and evaluated the correlation
      with clinical symptoms. Skin chambers were applied to the forearm skin which had
      been scratched with a needle, and extract of Dermatophagoides farinae (mite
      antigen) at 50 microns filters as a challenge. We measured the concentrations of
      histamine 2, 6, 12 and 24 hr after challenge. The skin chamber test was performed
      before and after beach camp therapy or hospitalization therapy. We treated 26
      children with beach camp therapy, and compared the effects with hospitalization
      in Tokyo (20 children). All the children in both groups showed results of
      mediator releasability in skin chamber was different in the two groups. The
      histamine levels were dramatically increased 24 hr after challenge with mite
      antigen. The levels of histamine in the chambers 24 hr after challenge decreased
      with treatment along with improvements in skin condition. A marked increase in
      histamine levels in the skin chamber fluids was observed after 24 hours, whereas
      no increase was observed when they were challenged with vehicle saline. After 7
      days of beach camp therapy, challenge with mite antigen produced only a very
      small increase in histamine levels even after 24 hours, which was significantly
      lower than the levels before therapy. In the cases involving hospitalization in
      Tokyo, histamine was observed to be increased at 24 hr (24.9 +/- 8.0 ng/ml SEM),
      similarly to the beach campgroup (19.0 +/- 7.3 ng/ml).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7518230
TI  - A study of factors contributing to bakers' allergy symptoms.
AB  - It has been known for many years that bakers, who work in an atmosphere filled
      with wheat flour and other grain products, often suffer from bronchial asthma and
      other allergy symptoms. We examined 36 cooks (males: 33, females: 3, average age:
      29.1 years) exposed to wheat products while baking bread or making
      confectionaries in a hotel. Their clinical symptoms were investigated, and
      peripheral blood eosinophils, serum IgE, wheat flour specific IgE, IgG1, IgG4,
      and antibodies to alpha-amylase and papain were measured. Clinical symptoms were
      present in some cases, the most common being rhinitis (13), itching and skin
      eruptions (8), ocular symptoms, including tearing, itching and conjunctival
      injection (8), and respiratory symptoms, including cough and sputum production
      (8). Wheat flour specific RAST was positive in 44.4% of cases. Peripheral
      eosinophils and wheat flour specific IgG1 levels were increased in those with
      positive RAST scores. Total IgE level and wheat flour specific IgG4 also seemed
      to be increased in those with positive RAST scores. Wheat flour specific IgG1 and
      IgG4 seemed to correlate positively with wheat flour specific IgE. The exposure
      duration correlated with neither total IgE nor wheat flour specific IgE. In those
      who were wheat flour RAST positive, wheat flour specific IgG1 levels correlated
      negatively with exposure duration. In RAST negative cases, however, there was no
      correlation. Similarly, there seemed to be a tendency for wheat flour specific
      IgG4 levels and exposure duration to correlate negatively in RAST positive cases.
      The subjects of this study initially worked in poorly ventilated areas.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7518231
TI  - [Anti-inflammatory effect of a traditional Chinese medicine, ren-shen-yang-rong
      tang (Japanese name: ninjin-youei-to), on alveolar macrophages stimulated by
      RANTES or TNF-alpha].
AB  - This study was performed to clarify the effect of RANTES or TNF-alpha on rabbit
      alveolar macrophages and the anti-inflammatory effect of NINJIN-YOUEI-TO on
      alveolar macrophages stimulated by RANTES or TNF-alpha. Phagocytosis of alveolar
      macrophages was dose-dependently stimulated by RANTES or TNF-alpha. However,
      phagocytosis of alveolar macrophages was completely suppressed to the basal level
      when alveolar macrophages were preincubated with NINJIN-YOUEI-TO at 37 degrees C
      for 20 min. These results suggest that NINJIN-YOUEI-TO has an anti-inflammatory
      effect on alveolar macrophages through a process still to be determined.

PMID- 7518233
TI  - Visual prognosis of eyes with submacular choroidal neovascularization.

PMID- 7518232
TI  - Intraoperative indocyanine green videoangiography in subretinal surgery.

PMID- 7518234
TI  - Studies of the intracellular Ca2+ levels in human adult skin mast cells activated
      by the ligand for the human c-kit receptor and anti-IgE.
AB  - The human c-kit receptor ligand, rhSCF, is the only cytokine known to be active
      on human mast cells, but its intracellular signal transduction pathway is still
      unknown. We compared the effect of rhSCF on intracellular Ca2+ levels in purified
      (> 70% pure) adult skin mast cells with two other immunologic stimuli, namely,
      anti-IgE and substance P. Both rhSCF (1 microgram/mL) and anti-IgE (3
      micrograms/mL) induced a rapid (< 20 sec) and sustained (T1/2 for decay > 10 min)
      increase in free cytosolic Ca2+ concentration. In contrast, substance P (5
      microM) elicited a very rapid (< 1 sec) and transient (T1/2 for decay congruent
      to 5 sec) rise in intracellular Ca2+ levels. Intracellular cAMP levels were then
      increased by pharmacologic means to examine the role of the cyclic nucleotide in
      controlling the Ca2+ response in skin mast cells. A combination of the general
      phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX) (200 microM) and the
      adenylate cyclase activator, forskolin (30 microM) was effective in inhibiting
      the Ca2+ response induced by rhSCF or anti-IgE (82 and 68% inhibition,
      respectively), while IBMX and forskolin alone were much less effective. The
      phosphodiesterase isozyme IV inhibitor, rolipram (10 microM), variably affected
      the increase in Ca2+ levels induced by anti-IgE, but it exerted a significant
      inhibitory activity on anti-IgE- or rhSCF-induced response in the presence of
      forskolin (30 micrograms/mL) (33 and 67%, respectively). Two different protein
      kinase C (PKC) activators TPA (200 nM) and bryostatin 1 (200 nM) similarly
      inhibited rhSCF- (22 and 32%, respectively) and anti-IgE-induced (24 and 32%)
      Ca2+ response. Finally, the kinase inhibitor genistein (30 micrograms/mL) was a
      somewhat more effective inhibitor of the rise in intracellular Ca2+ induced by
      rhSCF (100%) than that activated by anti-IgE (54%) (P < 0.05). These data
      indicate that rhSCF and anti-IgE may act on human mast cells through a common
      pathway to increase free cytosolic Ca2+ levels and this effect is similarly
      modulated by various drugs.

PMID- 7518237
TI  - [Immunohistochemical study of the olfactory mucosa and vomeronasal organ in rat,
      guinea pig and human fetus].
AB  - Immunohistochemical examination for neuron-specific enolase (NSE), S-100 protein
      and cytokeratin (CK) was performed in the olfactory mucosa and Jacobson's
      vomeronasal organ of rat, guinea pig and human fetus. The results indicated that:
      1) The combined immunohistostaining used in this study made it possible to
      examine the normal morphology and pathology of the olfactory mucosa; 2) The NSE
      immunoreactivity was recognized in the Jacobson's vomeronasal organ of the adult
      rats and guinea pigs. The vomeronasal organ of human fetuses below 5 months
      showed positive immunoreactivity for NSE, but the NSE immunoreactivity of the
      vomeronasal organ in fetuses above 7 months was not confirmed. So we conclude
      that human vomeronasal organ is possibly a regressive organ. It is unlikely to
      have any olfactory function as it does in rodent animals.

PMID- 7518236
TI  - [Demonstration of sulfite-group-specific IgE in patients with intolerance to
      preservatives].
AB  - On the basis of the selection of a population of patients intolerant to sulfites
      by the clinical history, a simple blind oral provocation test and a basophil
      activation test, we explored the basophil activation reaction induced by sulfites
      after passive sensitisation of blood donors basophils. We demonstrated that the
      percentages of activation obtained with a non covalent reagent (MBS-HSA), a
      covalent reagent (sulfonyl-HSA) and the optimal concentration of an anti-IgE were
      not significantly different. Human basophil activation was negativated by heating
      the transferred sera and by competition with a monoclonal human IgE. We also
      observed mediator release (histamine and LTC4) with a low frequency, histamine
      release being strictly related to the carrier protein concentration. In two
      cases, sulfite specific IgE were detected by ELISA. These results are in favour
      of the specificity and the IgE dependent nature of basophil activation induced by
      sulfites.

PMID- 7518235
TI  - Further characterization of the events involved in mitochondrial Ca2+ release and
      pore formation by prooxidants.
AB  - Addition of the prooxidant 3,5-dimethyl-N-acetyl-p-benzoquinone imine
      (3,5(Me)2NAPQI) to Ca(2+)-loaded mitochondria caused a rapid and extensive
      release of the sequestered Ca2+. Ca2+ release was accompanied by irreversible
      NAD(P)H oxidation and was followed by the release of adenine and pyridine
      nucleotides into the extramitochondrial medium; this is evidence of the opening
      of the pore in the inner mitochondrial membrane. Preincubation of the
      mitochondria with ADP, cyclosporin A (CSA), m-iodobenzylguanidine (MIBG) or Mg2+
      inhibited the prooxidant-induced Ca2+ release and prevented pore-opening. When
      mitochondria were preincubated with ruthenium red, Ca2+ release was only
      minimally stimulated by 3,5(Me)2NAPQI. However, increasing the concentration of
      the prooxidant caused release of an increasing fraction of the sequestered Ca2+.
      Alternatively, increasing the intramitochondrial Ca2+ load resulted in a lowering
      of the concentration of 3,5(Me)2NAPQI required for near complete Ca2+ release to
      occur. In the presence of ruthenium red, 3,5(Me)2NAPQI-induced Ca2+ release was
      accompanied by irreversible pyridine nucleotide oxidation and followed by the
      release of nucleotides into the extramitochondrial medium, events which were
      prevented on preincubation with CSA. Similarly, the addition of CSA, ADP or MIBG
      during 3,5(Me)2NAPQI-induced Ca2+ release arrested further Ca2+ release. In
      addition to their inhibitory effect on the 3,5(Me)2NAPQI-induced Ca2+ release,
      CSA, ADP or MIBG also decreased the rate of the basal, ruthenium red-induced
      mitochondrial Ca2+ release by 45-70%. It is proposed that the basal, ruthenium
      red-induced and the prooxidant-induced mitochondrial Ca2+ release occur through a
      common component that is sensitive to inhibition by CSA, ADP and MIBG and that is
      involved in mitochondrial pore formation. Furthermore, 3,5(Me)2NAPQI-induced pore
      opening does not involve Ca(2+)-cycling, but rather involves a site(s) that is
      (are) synergistically activated by Ca2+ and the prooxidant.

PMID- 7518238
TI  - Thromboangiitis obliterans.
AB  - Thromboangiitis obliterans (Buerger's disease) is an inflammatory obliterative,
      nonatherosclerotic, vascular disease that affects the small- and medium-sized
      arteries, veins, and nerves. It is causally related to tobacco use, although the
      exact mechanism is unknown. Its clinical presentation is manifested by distal
      arterial ischemia and superficial thrombophlebitis. Thromboangiitis obliterans
      usually becomes quiescent if the patient is able to stop smoking cigarettes.
      However, if smoking continues, amputation commonly results.

PMID- 7518239
TI  - Hepatic disease, the gastrointestinal tract, and rheumatic disease.
AB  - In previous years, this review concentrated on the relationship between pathology
      in the gastrointestinal tract and rheumatologic complaints associated with this
      pathology. This year, we have emphasized the relationship between hepatic
      disorders and rheumatologic complaints, although a resume of recent literature
      pertaining to the gastrointestinal tract and its rheumatologic consequences is
      also presented. We believe it is necessary to divert our primary focus of
      attention because of recent developments in identifying the extrahepatic effects
      of hepatitis C infection and the current interest in abnormalities of drug
      metabolism in various rheumatic and autoimmune disorders. These recent
      developments bring us full circle in incriminating not only bacterial and dietary
      antigens in the pathogenesis of the spondyloarthropathies but also viruses and
      exogenous chemicals as potential etiologic agents in genetically predisposed
      hosts, resulting in the development of a variety of diseases, including
      glomerulonephritis, vasculitis, Sjogren's syndrome, and systemic lupus
      erythematosus.

PMID- 7518240
TI  - Psychological effects of an epidemiological study of benign prostatic
      hypertrophy.
AB  - The psychological impact of an epidemiological study of benign prostatic
      hypertrophy (BPH) was assessed in a representative sample of practice list
      patients. Of the 889 men completing a general health self-report questionnaire
      previously validated in a screening programme, 75% knew nothing of problems of
      the prostate, and 84.5% were not at all worried about prostate problems prior to
      commencement of the study. Receiving the letter of invitation and the procedures
      neither increased nor reduced anxiety levels for 69% and 70% respectively. In the
      227 men referred to hospital for further investigation the procedure increased
      anxiety in 28%, decreased anxiety in 20%, and had no effect on the remainder. The
      sample of 137 (16%) men who, prior to interview, were in some way worried about
      problems of the prostate had significantly more urinary tract symptoms than those
      who were not at all worried about prostatic problems. Despite being worried about
      prostatic problems and having significant urinary symptoms, this group was no
      more likely to have attended a GP for investigation and/or treatment. Results are
      discussed in relation to the possible psychological effects of general health
      screening and the reluctance of men to attend for consultation despite awareness
      and concern regarding urinary symptomatology.

PMID- 7518241
TI  - Pharmacological treatment of benign prostatic hyperplasia.
AB  - Although surgery remains the standard treatment for benign prostatic hyperplasia
      there has been a rise in the number of available drugs for this condition. The
      current drug therapies appear to be useful for symptomatic short-term treatment,
      particularly for those patients unfit or unwilling to undergo surgical
      intervention. Further evaluation of the long-term effects of these treatments and
      their role in early disease is required, but drug therapy is likely to play a
      more important part in the management of this condition in the future.

PMID- 7518242
TI  - Molecular typing of hepatitis C virus genome from sera and liver tissues of
      patients with anti-HCV positive chronic liver disease.
AB  - The authors investigated the distribution of HCV genotypes in patients with
      various chronic liver diseases in Korea. Study population was 70 individuals,
      positive for second generation anti-HCV EIA, consisting of 37 cases with sporadic
      non-A, non-B (NANB) chronic hepatitis (CH), 12 NANB hepatocellular carcinoma, 16
      post-transfusion NANB hepatitis, 4 non-B blood donors and 1 healthy family member
      of a patient with sporadic CH. Molecular typing was performed by RT-nested PCR
      with type-specific primer sets deduced from the NS-5 region of HCV. The
      prevalence of type II was 75.0% and type III was 25.0% in sera. In liver tissues,
      type II HCV was shown in 63.0%, type III HCV in 3.7% and co-infections with type
      II and III HCV were observed in 18.5% of 27 samples biopsied. In the sera of
      patients with chronic hepatitis, typing results were relatively well correlated
      with those in tissues (75%), but type III could not be observed. Among 12 HCC
      patients, type III HCV appeared only in tissues, not in sera. These results
      suggest that type II HCV may be the major HCV type in Korea, and co-infections
      with type II and-III HCV may not be rare in chronic liver diseases with HCV.

PMID- 7518243
TI  - Plasma lipid concentrations in children with cystic fibrosis: the value of a high
      fat diet and pancreatic supplementation.
AB  - Impaired digestion of dietary fat is an almost universal feature of cystic
      fibrosis (CF) which results in low concentrations of essential fatty acids in
      plasma lipids. We have evaluated the effect of a high-lipid diet and pancreatic
      enzyme supplementation, using enteric-coated microsphere preparations, on plasma
      lipid concentrations in paediatric CF patients. Absorption of dietary lipid was
      comparable between control and CF subjects. This resulted in plasma cholesterol,
      triacylglycerol, total phosphatidylcholine and individual phosphatidylcholine
      molecular species concentrations in CF patients which were in the same range as
      those in controls. Normal values for these variables were also found in patients
      with clinically detectable liver disease. These results show that present dietary
      management of CF patients supports normal plasma lipid concentrations.

PMID- 7518244
TI  - Both RNA-binding domains in heterogenous nuclear ribonucleoprotein A1 contribute
      toward single-stranded-RNA binding.
AB  - Heterogenous nuclear ribonucleoproteins (hnRNPs) such as hnRNP A1 are tightly
      associated with heterogenous nuclear RNAs (hnRNAs) within eukaryotic nuclei and
      are thought to be involved in hnRNA processing and splice site selection. The NH2
      terminal two-thirds of hnRNP A1 contains two 92-amino acid RNA binding domains
      (RBDs) that are arranged in tandem and are more than 30% homologous with each
      other. Following this region is a flexible glycine-rich COOH-terminal domain. We
      have studied the nucleic acid binding properties of the two isolated RBDs
      (residues 1-92 and 93-184, respectively) and of A1 fragments corresponding to
      residues 1-184 and 1-196 (i.e., the latter fragment is called UP1) in order to
      evaluate their relative contributions to A1 binding. We have determined that the
      individual RBDs of A1 bind poly[r(epsilon A)], a fluorescent single-stranded RNA
      (ssRNA), with a surprisingly low apparent association constant of only 1.5 x
      10(4) M-1 (1-92) and 4.5 x 10(4) M-1 (93-184), respectively. We hypothesize that
      this low affinity represents a basal level of binding that is common to most RBD
      containing proteins. Oligonucleotide binding studies suggest the interaction site
      size for the 93-184 fragment is approximately 4 nucleotides or less and salt
      sensitivity studies indicate that only about 27% of the free energy of binding of
      this RBD derives from ionic interactions. Since the affinity of the 1-184
      fragment is at least 10-fold above that of either of its component RBDs, both
      must contribute to binding. This conclusion is further supported by the increased
      occluded site size of 1-184 (n = 14 +/- 2), as compared to its 93-184 RBD (n = 6
      +/- 1), and by the biphasic binding that was observed for the UP1:poly(U)
      interaction at pH 6.0. Our finding that the affinity of the 1-184 fragment is
      1000-fold less than the product of the affinities of its 1-92 and 93-184 RBDs is
      consistent with these domains being joined by a flexible linker. By comparing the
      affinities of the 1-184 fragment with that for A1, we conclude that together the
      two RBDs in A1 account for only 53% of the free energy of A1 binding. Comparative
      binding studies with UP1 demonstrate that the short region spanning residues 185-
      >195 represents an important determinant of the binding affinity of A1 and, since
      this region contains a site of dimethylation, it may provide a mechanism for
      regulating the affinity of A1 for specific nucleic acid targets.

PMID- 7518247
TI  - Detection and characterization of triple-helical pyrimidine-purine-pyrimidine
      nucleic acids with vibrational circular dichroism.
AB  - Vibrational circular dichroism (VCD) spectra were measured in the C = O
      stretching region for poly(U)*poly(A).poly(U), poly(dT)*poly(dA).poly(dT), and
      poly(U)*poly(dA). poly(dT). These VCD spectra of the triple-helical structure
      were dramatically different from those of the corresponding duplexes. The VCD
      indicates that a very similar base-pair structure is present in these triplexes.
      The same sign pattern was found for poly(C+)*poly(I).poly(C), which implies a
      generality of structure than can result from the steric constraint of the triple
      helix conformation. By contrast, the corresponding duplexes are quite different
      in terms of their VCD. The transitions between triplex, duplex, and single
      stranded forms were studied as a function of temperature and interpreted using
      factor analysis. The relative stabilities of the triplexes lie in the order RNA >
      DNA > hybrid. Nondegenerate dipole-coupling calculations for a U*A.U oligomer
      were carried out for the C = O stretching modes to model the spectral changes
      observed. The experimental absorbance spectra indicate that the bases have
      nonequivalent H-bonds which can be achieved if a reverse Hoogsteen base-pairing
      scheme is assumed. The computational VCD results with such a scheme were in
      better qualitative agreement with experiment than those using the expected
      Hoogsteen base-pairing scheme.

PMID- 7518246
TI  - The RNA-binding domain of transcription termination factor rho: isolation,
      characterization, and determination of sequence limits.
AB  - The function of transcription termination factor rho from Escherichia coli is
      dependent upon its ability to bind RNA. To delineate the extent of the RNA
      binding domain in the rho polypeptide, plasmid-borne copies of altered forms of
      the rho gene were expressed to yield truncated versions. These proteins were then
      isolated and assayed for their ability to bind an RNA oligonucleotide [oligo(C)8]
      using an ultraviolet light-induced cross-linking assay. A fragment consisting of
      the first 116 amino acid residues, rho(1-116), bound oligo(C)8 with nearly the
      same affinity and specificity as the intact protein. Smaller derivatives lacking
      5, 13, or 22 residues from the N terminus or with 2 fewer residues at the C
      terminus bound RNA with reduced affinity, while derivatives lacking 27 N-terminal
      residues or having just the first 109 residues were unable to bind RNA.
      Derivatives lacking N-terminal residues were considerably less soluble than rho(1
      116). The physical properties of rho(1-116) indicate that it possesses
      approximately 20% each of alpha-helix and beta-sheet and is monomeric in
      solution. Thus, the results show that this fragment, which contains an RNP1
      sequence motif, will be a good model for future physical-chemical studies of the
      protein-RNA interactions of rho.

PMID- 7518245
TI  - Purification and nucleic acid binding properties of a fragment of type C1/C2
      heterogeneous nuclear ribonucleoprotein from thymic nuclear extracts.
AB  - A single-strand nucleic acid binding protein (C/F) that has an apparent molecular
      weight of 12,000 on SDS-polyacrylamide gel electrophoresis and that was
      originally thought to be the 12-kDa alpha-subunit of the AB form of terminal
      deoxynucleotidyl transferase (TdT) from calf thymus has been purified and
      identified as a fragment of the type C1/C2 hnRNP proteins. On the basis of NH2
      terminal sequencing and mass spectrometric analysis, C/F contains approximately
      94 residues and spans from residue 9 to approximately residue 102 in the type
      C1/C2 hnRNP proteins. C/F is presumably produced in vitro via limited proteolysis
      of the type C1/C2 hnRNP proteins following cell disruption. Since C/F corresponds
      almost exactly to the approximately 90-residue conserved ribonucleoprotein
      binding domain (RBD) that is shared by many eukaryotic RNA binding proteins, it
      provided an opportunity to better characterize the domain structure of the type
      C1/C2 hnRNP proteins and to compare the nucleic acid binding properties of the
      type C1/C2 and A1 [see Shamoo et al. (1994) Biochemistry, preceding paper in this
      issue] RNA binding domains. Like the type A1 RBD, the type C1/C2 RBD has an
      apparent occluded site size of 6-7 nucleotides. The type C1/C2 RBD binds non
      cooperatively to homopolynucleotides and has preferential affinity for RNA and
      for single as opposed to double-stranded nucleic acids. The type C1/C2 RBD has
      about a 100-fold higher affinity than the type A1 RBD does for RNA and some of
      this increased affinity results from additional ionic interactions. The latter
      account for approximately 50% of the free energy of binding of the type C1/C2
      RBD. While the type C1/C2 hnRNP proteins exist in vivo as a very tight tetramer
      with the structure (C1)3C2 [Barnett et al. (1989) Mol. Cell. Biol. 9, 492-498],
      the isolated type C1/C2 RBD is a monomer. Hence, the determinants for
      tetramerization appear to lie outside the type C1/C2 RBD. Phenylalanine 19 was
      identified as the only point of photochemical cross-linking of the type C1/C2 RBD
      to [d(T)]8. This residue corresponds to the major site of cross-linking of the A1
      RBD to [d(T)]8 [Merrill, B. M., Stone, K. L., Cobianchi, F., Wilson, S. H., &
      Williams, K. R. (1988) J. Biol. Chem. 263, 3307-3313].(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7518248
TI  - Molecular design of DNA-directed ligands with specific interactions: solution NMR
      studies of the interaction of a m-hydroxy analogue of Hoechst 33258 with
      d(CGCGAATTCGCG)2.
AB  - We have used one-dimensional (1D) and two-dimensional (2D) proton nuclear
      magnetic resonance spectroscopy at 600 MHz for structural analysis of the complex
      formed between d(CGCGAATTCGCG)2 and 2-[2-(3-hydroxyphenyl)-6-benzimidazoyl]-6-(1
      methyl-4-piperazinyl) benzimidazole (meta-Hoechst). This analogue differs from
      Hoechst 33258 only in the location of its meta rather than para phenolic hydroxyl
      group and was designed to introduce the possibility of intermolecular hydrogen
      bonding to DNA via the phenol. Complex formation was shown to be 1:1 at 25
      degrees C in phosphate buffer in D2O by 1D NMR spectroscopic titration of a
      solution of d(CGCGAATTCGCG)2 with meta-Hoechst. From 1D NMR spectroscopy the
      observed perturbations of the assigned chemical shifts of the oligonucleotide
      observed on binding meta-Hoechst could be used to locate the ligand in the
      central AATT stretch. By means of 2D NMR spectroscopic techniques, over 400
      proton-proton NOEs were defined within the complex. DNA nonexchangeable resonance
      assignments were made using the sequential assignment method and NOESY. Binding
      the unsymmetrical ligand lifted the C2v symmetry of the DNA. Exchangeable
      hydrogens were assigned from NOESY data acquired in 85% H2O/15% D2O medium for
      the complex and showed differences between the Hoechst 33258 and meta-Hoechst
      complexes with d(CGCGAATTCGCG)2. The location of meta-Hoechst in the minor-groove
      AATT region was triangulated using 32 intermolecular NOEs determined for the
      complex. From the intermolecular NOEs involving the aromatic C-H protons of the
      phenolic ring of meta-Hoechst, it was clear that this region of the molecule did
      not rotate freely within the minor groove on the NMR time scale and was oriented
      with its hydroxyl group toward the floor of the minor groove, in line with the
      occurrence of the predicted hydrogen bonding between it and the DNA. The pKa of
      the N3H proton of meta-Hoechst in its bound state in this complex was measured as
      6.1 by NMR spectroscopy, a value slightly elevated relative to estimates
      (approximately 5.2) of the pKa of this proton for the free ligand. Molecular
      mechanics and the distance restraints provided by the intermolecular NOEs were
      used in molecular modeling of the meta-Hoechst/d(CGCGAATTCGCG)2 complex, and the
      distances in the model were consistent with the formation of hydrogen bonds
      involving the m-OH group of meta-Hoechst and the DNA.

PMID- 7518249
TI  - Structure and dynamics of the human granulocyte colony-stimulating factor
      determined by NMR spectroscopy. Loop mobility in a four-helix-bundle protein.
AB  - Recombinant 15N- and 13C-labeled human granulocyte colony-stimulating factor (rh
      metG-CSF) has been studied by 2D and 3D NMR using uniformly labeled protein, as
      well as residue-specific 15N-labeled samples. Assignment of 90% of the backbone
      resonances and 85% of side-chain resonances has enabled the determination of both
      the secondary and tertiary structures of the protein. The fold is similar to
      those of the human growth hormone and other growth factors. Four stretches of
      helices were identified between residues 11 and 41 (helix A), 71 and 95 (helix
      B), 102 and 125 (helix C), and 145 and 170 (helix D), which form a left-handed
      four-helix bundle with helices A and B aligned parallel to one another (up-up)
      and antiparallel to helices C and D (down-down). An additional short fifth helix
      (E) is part of the AB loop connecting helices A and B. Examination of the
      protein's relaxation behavior, based on the model-free approach of Lipari and
      Szabo, shows that the G-CSF backbone has a well-defined structure of limited
      conformational flexibility in helices. In contrast, the long loop connecting
      helices C and D exhibits substantial fast internal motion compared to the overall
      rotational correlation time of the whole molecule, which is on the order of 13
      ns.

PMID- 7518251
TI  - Survival in lung reperfusion injury is improved by an antibody that binds and
      inhibits L- and E-selectin.
AB  - The selectins are a three-member family of leukocyte, platelet, and endothelial
      cell adhesion proteins that mediate leukocyte traffic into normal and inflamed
      tissues. P-selectin is expressed by endothelial cells and platelets, E-selectin
      by endothelial cells, and L-selectin by circulating leukocytes. To determine if
      selectin-mediated leukocyte adhesion influences the development of lung
      reperfusion injury, we studied hemodynamics and respiratory and inert gas
      exchange in sheep subjected to 3-hour in situ left lung ischemia followed by 6
      hour left lung reperfusion with the right lung excluded. Ten minutes before
      reperfusion, eight animals received EL-246 (1 mg/kg intravenously), a novel
      antihuman selectin antibody that recognizes and blocks both L- and E-selectin and
      cross-reacts in sheep. Eight control animals with ischemia received no treatment,
      whereas three received an isotype-matched antihuman L-selectin antibody that does
      not cross-react in sheep (DREG-56, 1 mg/kg intravenously). Eight sham control
      sheep underwent an identical operative procedure but were never subjected to
      ischemia. Volume-cycled, pressure-limited (20 cm H2O) mechanical ventilation was
      consistent in all animals throughout the experiment. Six-hour survival in EL-246
      recipients (100%) was significantly higher than in either ischemic control sheep
      (37.5%) or DREG-56 recipients (33.3%), but gravimetric lung water was equivalent
      in EL-246 recipients (5.9 +/- 1.7 ml/kg), ischemic control sheep (8.3 +/- 3.0
      ml/kg), and DREG-56 recipients (9.1 +/- 2.6 ml/kg).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7518253
TI  - The alpha 2-macroglobulin receptor and epithelial glycoprotein-330: two giant
      receptors mediating endocytosis of multiple ligands.

PMID- 7518254
TI  - Selectins as potential targets of therapeutic intervention in inflammatory
      diseases.

PMID- 7518250
TI  - Influence of Na+ on conformational states in membrane-bound renal Na,K-ATPase.
AB  - Conformational states of the Na,K-ATPase and rates of transition between these
      are studied using the fluorescent dye eosin as a marker for the Na+ form (E1) and
      occlusion of 86Rb+ as a marker for the K+ form (E2). The aim of the present paper
      is to propose that the E1 form of the Na,K-ATPase can be liganded with a number
      of Rb+ and Na+ ions and that only some of these E1 forms bind eosin and thus
      probably nucleotides with high affinity. Experiments are performed with Na,K
      ATPase isolated from pig kidney. Binding of eosin occurs only when Na+ is present
      at millimolar concentrations, and the observed rate of binding is slow when Rb+
      is present. The rate of eosin binding after a sudden increase in the Na+
      concentration is about the same as the rate of deocclusion of Rb+, suggesting
      that eosin monitors the rate of the E2 to E1 transition. Titrations of eosin
      fluorescence with Na+ indicate that binding of more than one Na+ occurs when high
      affinity eosin binding takes place. With 0.05 mM RbCl and 4 mM NaCl present, the
      Na,K-ATPase is a mixture of at least two enzyme species which do not bind eosin
      with high affinity. One species is the E2 form with Rb+ occluded, and transition
      of this form to E1 gives rise to a small observed rate constant for eosin binding
      when the Na+ concentration is suddenly increased to about 25 mM.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7518255
TI  - Effect of the nucleotide-37 on the interaction of tRNA(Phe) with the P site of
      Escherichia coli ribosomes.
AB  - The method of anticodon loop replacement has been used to make derivatives of
      yeast tRNA(Phe) with the substitution at position 37 (tRNA(Phe)GAAA) and at the
      anticodon(tRNA(Phe)GCAG). A quantitative study of the interaction of various
      types of deacylated yeast tRNA(Phe) (tRNA(Phe)+Y, tRNA(Phe)GAAA, tRNA(Phe)-Y)
      with the P site of the [70S ribosome*poly(U)]-complex was carried out at
      different Mg2+ concentrations and temperatures. The presence and nature of the
      nucleotide situated at the 3'-end of the anticodon are essential for such
      interaction in E coli ribosomes. Replacement of the Y base with the unmodified
      adenosine decreases the interaction enthalpy from 39 kcal/mol to 24 kcal/mol,
      whereas its removal reduces the interaction enthalpy to 16 kcal/mol. Replacement
      of the second anticodon nucleotide, adenosine, with cytosine further reduces the
      enthalpy to 6 kcal/mol, which is typical of tRNA-P site interaction in the
      absence of poly(U). In the absence of poly(U) the affinity of tRNA(PheY) for the
      P site of the 70S ribosome is five times lower than the affinity of tRNA(Phe+Y)
      or tRNA(Phe)GCAG. Thus, in the ribosome the modified nucleotide stabilizes the
      codon-anticodon interaction through its stacking interaction with the codon
      anticodon base stack. In addition, this decreases the free energy of binding as a
      result of the interaction of the modified nucleotide itself with the hydrophobic
      center of the P site.

PMID- 7518252
TI  - Comparison of cardiac rejection in heart and heart-lung concordant
      xenotransplantation.
AB  - Clinical observations indicate that in heart-lung grafting the heart is less
      frequently rejected than in heart grafting alone. In addition, our results of
      allograft experiments indicated that the graft survival period is longer in the
      former (11.8 +/- 0.8 days versus 6.6 +/- 0.5 days, p < 0.05), suggesting that the
      simultaneous grafting of the lung in heart-lung allografts suppressed the
      rejection of the grafted heart. We assessed the effect of simultaneous lung
      xenografting, splenectomy, and FK506 treatment on the survival of the xenografted
      heart in a concordant model. With Wistar rats as recipients and golden hamsters
      as donors, cardiac survival was compared between en bloc heart-lung and heart
      heterotopic xenografts. The cardiac survival of heart-lung and heart xenografts
      was not prolonged by FK506 treatment alone but was prolonged by splenectomy.
      Splenectomy plus FK506 (1.0 mg/kg/day) showed suppression of antibody production
      and a remarkable synergistic effect in prolongation (33.2 +/- 7.4 days versus
      36.8 +/- 8.1 days) in heart-lung and heart xenografts. Simultaneous lung
      xenografting significantly shortened the survival period of the xenografted heart
      in splenectomy plus FK506 (0.5 mg/kg/day) recipients (4.8 +/- 0.8 days versus 9.0
      +/- 3.5 days, p < 0.05), in contrast to the prolongation of the survival period
      of the grafted heart in heart-lung allografting.

PMID- 7518257
TI  - Characterization and expression of a gene encoding serine tRNA5 from Escherichia
      coli.
AB  - The genes for translational components frequently are located together on the
      Escherichia coli genome. We have reported previously that the gene for a serine
      tRNA lies directly downstream from infA, the gene encoding initiation factor IF1.
      Here we characterize this tRNA gene, named serW. The serW gene expresses a minor
      form of serine tRNA(GGA) which recognizes the most frequently used serine codons,
      UCC and UCU. Two promoters were identified by S1 nuclease mapping: P1, which lies
      about 72 bp upstream from the structural gene; and P2, which lies about 35 bp
      upstream. Expression from P1 and P2 is comparable under conditions of rapid
      growth. The P2 promoter is followed by a GC-rich element characteristic of
      promoters regulated by ppGpp. A putative hairpin structure followed by a stretch
      of U residues about 25 nucleotides following the mature tRNA sequence resembles a
      rho-independent termination signal. The upstream gene, infA, is followed by a
      transcriptional terminator, but S1 mapping shows considerable readthrough. This
      serW expression appears to rely both on its own promoters and on promoters
      further upstream. The downstream gene, encoding an unidentified protein of about
      100 kDa, is expressed in the opposite orientation and also is followed by a
      termination signal. Therefore serW is expressed both as a monocistronic gene and
      in combination with infA.

PMID- 7518258
TI  - Measurement of prostate-specific antigen in serum using four different
      immunoassays.
AB  - This paper summarises the results of a comparison of the Serono SR1, Ciba Corning
      ACS 180, Abbott IMx and Hybritech Tandem-R prostate-specific antigen assays. One
      hundred serum pools were assayed using the four methods. Linear regression
      analysis of the data showed that, although overall correlations were good,
      different assays gave different prostate-specific antigen concentrations. Tandem
      R and SR1 assays gave very similar prostate-specific antigen values; in general,
      the ACS assay gave higher prostate-specific antigen values than the IMx assay
      gave lower prostate-specific antigen values than the established Tandem-R assay.
      Following fractionation of serum from prostate cancer patients, all immunoassays
      detected several immunoreactive prostate-specific antigen forms. The major
      immunoreactive form (> 88% of immunoreactivity) had an apparent molecular size of
      M(r) approximately 100,000 and is likely to be a complex of prostate-specific
      antigen with alpha 1-antichymotrypsin; two minor forms had apparent molecular
      sizes of M(r) approximately 30,000 (probably free prostate-specific antigen) and
      200,000 (probably prostate-specific antigen complexed to high molecular mass anti
      proteases). From this study there is no evidence that polyclonal/monoclonal
      antibody immunoassays are to be preferred to monoclonal/monoclonal antibody
      immunoassays for the determination of free prostate-specific antigen in serum.

PMID- 7518256
TI  - Determination of the HNK-1 epitope (3-sulphated glucuronic acid) in intact
      chondroitin sulphates by ELISA. Application to squid skin proteoglycans and their
      oversulphated carbohydrate structures.
AB  - The reactivity of the HNK-1 monoclonal antibody to chondroitin sulphates and
      derived disaccharides was studied using an ELISA inhibition test. The antibody
      readily reacted with its specific epitope (3-sulphated glucuronic acid) in intact
      chondroitin sulphates as well as with the equivalent oversulphated delta 4
      disaccharides obtained by chondroitinase digestion and identified as sulphated at
      C-3 of the hexuronate. It is showed that by using the oversulphated delta 4
      disaccharides as standards in an ELISA inhibition test, the amount of 3-sulphated
      glucuronic acid can be estimated also in the polymer preparations. When applying
      this ELISA test to the PG populations isolated from squid skin, most of the
      oversulphation seen in HPLC analyses of these preparations was found to be
      associated with 3-sulphation of the glucuronic acid.

PMID- 7518259
TI  - Cytokeratin 19 fragment CYFRA 21-1 compared with carcinoembryonic antigen,
      squamous cell carcinoma antigen and neuron-specific enolase in lung cancer.
      Results of an international multicentre study.
AB  - The diagnostic value of the water-soluble cytokeratin 19 fragment CYFRA 21-1 in
      lung cancer was assessed in comparison with carcinoembryonic antigen, squamous
      cell carcinoma antigen, and neuron-specific enolase. The cut-off value, defined
      as 95% specificity versus a group of 526 patients suffering from benign chest
      diseases, was set at 3.3 micrograms/l for cytokeratin 19 fragment CYFRA 21-1
      (carcinoembryonic antigen: 7.8 micrograms/l, squamous cell carcinoma antigen: 1.9
      micrograms/l, neuron-specific enolase: 13.7 micrograms/l). Elevated pretreatment
      cytokeratin 19 fragment CYFRA 21-1 concentrations were recorded: in 112 of 244
      (46%) patients with all histological types of lung cancer (carcinoembryonic
      antigen: 32%, squamous cell carcinoma antigen: 25%, neuron-specific enolase:
      28%), in 89 of 177 (50%) patients with non-small cell lung cancer
      (carcinoembryonic antigen: 33%, squamous cell carcinoma antigen: 24%, neuron
      specific enolase: 12%), in 47 of 81 (58%) patients with squamous cell carcinoma
      (carcinoembryonic antigen: 23%, squamous cell carcinoma antigen: 32%, neuron
      specific enolase: 14%), in 27 of 63 (42%) patients with adenocarcinoma
      (carcinoembryonic antigen: 44%, squamous cell carcinoma antigen: 14%, neuron
      specific enolase: 9%), in 15 of 33 (45%) patients with other non-small cell lung
      cancer (carcinoembryonic antigen: 36%, squamous cell carcinoma antigen: 24%,
      neuron-specific enolase: 14%), and in 20 of 55 (36%) patients with small cell
      lung cancer (carcinoembryonic antigen: 32%, neuron-specific enolase: 77%). Three
      of 12 patients with undefined histological type showed cytokeratin 19 fragment
      CYFRA 21-1 elevations. The best performance in terms of sensitivity and
      diagnostic accuracy was attained with the cytokeratin 19 fragment CYFRA 21-1 test
      in squamous cell carcinoma. In small cell lung cancer neuron-specific enolase was
      confirmed to be superior to the other markers. Cytokeratin 19 fragment CYFRA 21-1
      concentrations increased with the extent of the malignant disease in non-small
      cell lung cancer. The positivity rate of cytokeratin 19 fragment CYFRA 21-1 in
      tumour stage TNM I was only 23% (carcinoembryonic antigen: 23%, squamous cell
      carcinoma antigen: 14%), i.e. the markers under study cannot be used for the
      diagnosis of early stage disease. Cytokeratin 19 fragment CYFRA 21-1
      differentiated significantly between squamous cell carcinoma and the other
      histological types (p < 0.01). In addition, cytokeratin 19 fragment CYFRA 21-1
      distinguished significantly the operable group TNM I-IIIa from inoperable TNM
      IIIb-IV (p < 0.05), but not TNM IIIa from IIIb. Out of 177 patients with non
      small cell lung cancer, 90 individuals were monitored after surgery.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7518260
TI  - Differential expression and regulation of cytokine mRNAs in normal human CD45R T
      cell subsets.
AB  - Cytokine mRNA expression was analyzed by reverse transcriptase (RT)/PCR in
      extensively purified normal peripheral CD4+CD45R T cell subsets. Both CD45RA+ and
      CD45 RO+ populations produced mRNAs for interleukin (IL)-2, IL-2 receptor (alpha
      chain), IL-6 receptor and tumour necrosis factor (TNF)-beta within 3-4 h of
      activation. Whilst IL-3 and RANTES were also expressed in both subsets, CD45RO+
      cells were clearly the major producers of these cytokines. In contrast, mRNA
      transcripts for IL-1 alpha, IL-4, IL-5, IL-6, IL-10, interferon gamma (IFN-gamma)
      and the T cell receptor for IL-1 were almost exclusively induced in CD45RO+ T
      cells. A population of CD4+ T cells co-expressing intermediate levels of both
      CD45RA and CD45RO, namely CD45RA+/CD45RO+, appeared to be the major producers of
      IL-6. Addition of cycloheximide (CHx) 4 h after T cell activation resulted in
      substantial superinduction of IL-2 mRNA in the CD4+CD45RO+ population but had
      little effect on CD4+CD45RA+ cells. Taken together, these results show that
      normal CD4+CD45R T cell subsets exhibit distinct cytokine mRNA profiles and that
      these differ from the patterns displayed by Th1 and Th2 type T helper clones.
      Furthermore, they suggest for the first time that IL-2 mRNA turnover is
      differentially regulated in CD45R T cell subsets.

PMID- 7518261
TI  - Levels of serum colony-stimulating factors (CSFs) in patients on long-term
      haemodialysis.
AB  - We measured the levels of colony-stimulating factors (G-CSF, M-CSF and GM-CSF)
      and several cytokines in paired sera obtained from 51 patients (33 males and 18
      females; mean age: 53 years) on long-term haemodialysis (HD). The mean pre-HD G
      CSF level was 22.7 +/- 21.7 pg/ml and the post-HD level was 40.3 +/- 54.4 pg/ml.
      The mean pre-HD M-CSF level was 2.4 times higher than normal at 1287 +/- 380
      U/ml, and it increased to 1644 +/- 456 U/ml after HD (r = 0.83). GM-CSF was not
      detectable in any of the serum samples. IL-1 beta was detectable in 38 pre-HD
      sera at a mean level of 57.1 +/- 21.8 pg/ml, but was rarely detected after HD.
      TNF-alpha was not usually detected. When the CSF levels were divided by the
      product of the serum total protein concentration and body weight, the post-HD
      value for G-CSF was almost always greater than the pre-HD value and there was an
      improved pre-post correlation (r = 0.69). In the transformed pairs of M-CSF
      level, the post-HD value did not differ much from the pre-HD value, and a strong
      pre-post correlation was noted (r = 0.94). These results suggest that the serum G
      CSF level is not affected by chronic renal failure, although HD may induce an
      increase of G-CSF. In the case of M-CSF, however, impaired renal metabolism
      and/or excretion may increase the serum concentration, but it is not modulated by
      haemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518262
TI  - Expression of c-kit and kit ligand at the human maternofetal interface.
AB  - Kit ligand, or stem cell factor, is a recently identified growth factor, which
      binds to and activates the c-kit proto-oncogene, and which has been shown to act
      synergistically with other haematopoietic growth factors in the bone marrow. We
      have previously shown that several isoforms of kit ligand, which arise due to
      alternative splicing, are expressed in human placenta. In order to elucidate the
      role of c-kit and its ligand during human placental development we have
      investigated the expression of c-kit and kit ligand in human first trimester and
      term placenta as well as in pregnant and non-pregnant endometrium, by
      immunocytochemistry and flow cytometric analysis. In non-pregnant endometrium no
      expression of kit ligand was seen. By contrast, in first trimester decidua, kit
      ligand was strongly expressed by the arterial media of maternal blood vessels.
      Kit ligand was also expressed throughout pregnancy by invasive fetal extravillous
      trophoblast, and by fetal fibroblasts within the placental villi. c-kit was found
      to be expressed on Hofbauer cells within the chorionic villi, and by decidual
      macrophages at all stages in pregnancy. c-kit was also detected on the small
      CD56dim subset of uterine large granular lymphocytes which form the major
      leukocyte population in human first trimester decidua. Our results suggest that
      kit ligand may be involved in the regulation of fetal macrophages, and in
      particular in signalling between invading extravillous trophoblast which
      expresses kit ligand, and maternal leukocytes bearing the c-kit receptor.

PMID- 7518263
TI  - Characterization of recombinant human acidic fibroblast growth factor:
      comparative studies with bovine acidic fibroblast growth factor.
AB  - Recombinant human acidic fibroblast growth factor (haFGF) was purified from E.
      coli lysate by heparin-sepharose affinity chromatography. The purified haFGF
      exhibited potent mitogenic activity in stimulating DNA synthesis in 3T3 cells and
      this activity could be significantly increased by heparin. By analysis of
      mitogenic activity and immunological properties, a marked difference was found
      between haFGF and bovine aFGF (baFGF). The main difference was that the heparin
      dependence of haFGF was stronger than that of baFGF.

PMID- 7518264
TI  - Histopathological features of liver disease in alpha 1-antitrypsin deficiency.

PMID- 7518266
TI  - Molecular pharmacology of serotonin receptors.
AB  - The serotonin system has long been thought to play a role at several steps in the
      cycle of alcohol abuse. Initial motivation may be triggered by anxiety, which may
      exhibit a serotonergic component (5-HT1A receptor). Alcohol can potentiate the
      opening of 5-HT3 receptor ion channels, and agents which elevate serotonergic
      tone, including serotonergic agonists, uptake inhibitors and releasers, have
      shown promise in assisting with recovery from alcoholism. In this review, recent
      advances in serotonin receptor research are presented, with a special emphasis on
      the impact and interpretation of molecular biological data. Genetic and
      pharmacological concepts of receptor subtypes are reviewed and related to a new
      classification system for the 14 currently recognized subtypes of serotonin
      receptors. The current and likely future impact on drug design of the molecular
      approach to serotonin receptors is discussed. Finally, the question of why there
      are so many serotonin receptor subtypes is examined, along with possible roles of
      multiple G protein and second messenger pathways, and their effect on conserved
      domains of these receptor proteins.

PMID- 7518267
TI  - Lysine residues in bee venom phospholipase A2 are important for binding to human
      monoclonal or polyclonal antibodies of the IgG4 isotope.
AB  - Discontinuous antigenic sites on bee venom phospholipase A2 (PLA) have been
      mapped using human monoclonal antibodies or human polyclonal serum antibodies
      (hpAbs) of the IgG4 isotype from beekeepers or of the IgE isotype from
      individuals allergic to PLA. Lysine residues of PLA have been specifically
      modified by acetylation or acylation by treatment with citraconic anhydride of
      their epsilon-amino groups to analyze their role in antigen-antibody binding.
      After the modifications, the binding of PLA to the human monoclonal antibodies is
      lost, whereas the binding to IgG4 hpAbs is significantly decreased. In contrast,
      the effect on the binding of PLA to IgE hpAbs appears to be more heterogeneous.
      The data indicate the importance of lysine residues as being part of B cell
      epitopes in PLA-specific antibodies of the IgG4 isotype, but less so for those of
      the IgE isotype.

PMID- 7518265
TI  - Serotonin, violent behavior and alcohol.
AB  - At the NIAAA intramural research program, in collaboration with investigators at
      the Department of Psychiatry, University of Helsinki, we have mounted an
      extensive research program on early onset male alcoholism. A central serotonergic
      deficit is common among these patients. This finding has led to behavioral,
      biochemical, physiological and molecular genetic studies on the serotonin system
      in early onset, antisocial and violent male alcoholics and in appropriate control
      populations. The results of the studies completed by the fall of 1993 are
      summarized in this communication.

PMID- 7518268
TI  - Cultivar-specific epitopes in date palm (Phoenix dactylifera L.) pollenosis.
      Differential antigenic and allergenic properties of pollen from ten cultivars.
AB  - Pollen from ten staminate cultivars of the date palm (Phoenix dactylifera L.)
      were compared for their antigenic and allergenic potentials. Crude extracts from
      the various cultivars were tested in 6 atopic patients with confirmed allergy to
      date pollen in order to determine any differences or similarities in the
      antigenic and allergenic properties of these cultivars. Results of skin prick
      tests, ELISA, IgG and IgE immunoblot analyses, peripheral blood lymphocyte
      proliferation and concomitant interleukin-4 (IL-4) production indicated inter
      cultivar heterogeneity. One of the cultivars, No. 8, failed to elicit any skin
      test reactivity or bind IgE in atopic sera as determined by ELISA, immunoblotting
      or any of the other parameters examined. However, there were individual
      differences in patient responses but in the main and contrary to the results
      obtained with cultivars No. 1, 2, 4, 5 and 8, five of the cultivars, namely No.
      3, 6, 7, 9 and 10, showed more enhanced differential antigenic and allergenic
      properties. Our results strongly indicate that the antigenicity and allergenicity
      of date palm pollen is more of a cultivar-specific phenomenon than a species
      specific phenomenon, which is governed by the number, quantities or both of the
      major allergen epitopes possessed by that variety or cultivar.

PMID- 7518269
TI  - Thimerosal induces toxic reaction in non-sensitized animals.
AB  - The effects of injection of thimerosal solution on nonsensitized animals was
      investigated. Intrafootpad injection of thimerosal solution in nonsensitized mice
      resulted in a swelling response which peaked 1 h after injection and lasted for
      more than 24 h. Histopathological examination showed that there were severe edema
      and infiltration of polymorphonuclear neutrophils at the site of injection. An
      increased vascular permeability was observed after cutaneous injection of
      thimerosal solution on the back of nonsensitized rats. Since mercuric chloride
      and methyl mercury induced severer reactions, and thiosalicylic acid had no
      effect, mercury contained in thimerosal would have caused the reactions observed
      in this study. These results suggest that part of these hypersensitivity
      reactions against thimerosal observed among patients were possibly induced by the
      toxic effect of thimerosal. Therefore, thimerosal contained as a preservative in
      vaccine may augment the side-effects of the vaccination.

PMID- 7518270
TI  - Demonstration of the presence of coeliac-activating gliadin-like epitopes in
      malted barley.
AB  - A peptide B3144, derived after peptic tryptic digestion of alpha-gliadin and
      corresponding to residues 3-56 from the coeliac-activating domain I, was
      previously used to produce monoclonal antibodies. A dot immunobinding assay was
      developed using these antibodies to detect gluten in wheat, rye, barley and oats.
      The limit of sensitivity of the assay was 1 microgram/ml for unfractionated wheat
      gliadin and rye prolamins, and 5 micrograms/ml for barley and oat prolamins.
      Extracts of flours from coeliac non-toxic rice, maize, millet and sorghum gave
      negative results. Malt, which represents a partial hydrolysate of barley
      prolamins, was shown to contain the equivalent of 100-200 mg of barley
      prolamins/100 g of malt. The assay demonstrates the presence of intact epitopes
      from the coeliac-activating domain I of alpha-gliadins in malted barley,
      suggesting toxicity.

PMID- 7518271
TI  - The genetic and functional basis of HIV-1 resistance to nonnucleoside reverse
      transcriptase inhibitors.
AB  - The nonnucleoside reverse transcriptase (RT) inhibitors are structurally diverse
      compounds that are specific inhibitors of the human immunodeficiency virus type 1
      RT enzyme. The compounds are largely functionally identical and bind to a common
      site in the enzyme. HIV-1 variants that exhibit reduced susceptibility to these
      inhibitors have been derived in cell culture and, more recently, from HIV-1
      infected patients undergoing experimental therapy. The variants express amino
      acid substitutions at RT positions that apparently interact directly with the
      inhibitors. Effects of specific substitutions at these positions vary among the
      compounds, suggesting subtle differences in how the compounds physically interact
      with the enzyme.

PMID- 7518272
TI  - Recombination between Sindbis virus RNAs.
AB  - The Sindbis virus RNA genome is divided into two modules--one coding for the
      nonstructural protein genes and the other coding for the structural protein
      genes. In our studies of recombination, the two parental RNAs were defective in
      different modules. Analysis of the recombinant RNAs demonstrated that the
      parental RNAs each contributed its intact module and that the crossovers occurred
      within the defective modules. The recombinational events giving rise to
      infectious virion RNAs could create deletions, rearrangements or insertions as
      long as they occurred outside of the functional module. These crossovers produced
      RNA genomes that contained two functional subgenomic RNA promoters.

PMID- 7518273
TI  - Nodavirus RNA replication: mechanism and harnessing to vaccinia virus
      recombinants.
AB  - In order to harness RNA replication for the amplification of mRNAs expressed from
      recombinant vectors and vaccines, we constructed a VV recombinant that expressed
      the RNA replicase encoded in the larger genomic segment of the nodavirus FHV.
      When both termini of the VV-derived transcript were correct, the encoded enzyme
      replicated its own mRNA, and replication dominated the RNA synthetic capacity of
      the cell. The smaller genomic segment of FHV could also be replicated by the
      enzyme when supplied in trans, either by coinfection with another VV recombinant
      or by transfection of an appropriate plasmid. However, two requirements had to be
      fulfilled for replication of the smaller FHV RNA segment. The first was the prior
      replication of the larger genomic segment, which was interpreted as a mechanism
      to achieve sufficient replicase synthesis before the onset of coat protein
      synthesis. The second was the presence in the smaller genomic RNA of an internal
      region between about nucleotides 525-620. Work is in progress to elucidate the
      reasons for these requirements for RNA 2 replication.

PMID- 7518274
TI  - Assembly of tobacco mosaic virus and TMV-like pseudovirus particles in
      Escherichia coli.
AB  - High-level expression of plant viral proteins, including coat protein (CP), is
      possible in Escherichia coli. Native tobacco mosaic virus (TMV) CP expressed in
      E. coli remains soluble but has a non-acetylated N-terminal Ser residue and
      following extraction, is unable to package TMV RNA in vitro under standard
      assembly conditions. Changing the Ser to Ala or Pro by PCR-mutagenesis did not
      confer assembly competence in vitro, despite these being non-acetylated N-termini
      present in two natural strains of TMV. All TMV CPs made in E. coli formed stacked
      cylindrical aggregates in vitro at pH 5.0 and failed to be immunogold-labelled
      using a mouse monoclonal antibody specific for helically assembled TMV CP. TMV
      self-assembly has been studied extensively in vitro, and an origin of assembly
      sequence (OAS) mapped internally on the 6.4 kb ssRNA genome. Pseudovirus
      particles can be assembled mono- or bi-directionally in vitro using virus-derived
      CP and chimeric ssRNAs containing the cognate TMV OAS, but otherwise of unlimited
      length and sequence. Studies on plant virus assembly in vivo would be facilitated
      by a model system amenable to site-directed mutagenesis and rapid recovery of
      progeny particles. When chimeric transcripts containing the TMV OAS were co
      expressed with TMV CP in vivo for 2-18 h, helical TMV-like ribonucleoprotein
      particles of the predicted length were formed in high yield (up to 7.4
      micrograms/mg total bacterial protein). In addition to providing a rapid,
      inexpensive and convenient system to produce, protect and recover chimeric gene
      transcripts of any length or sequence, this E. coli system also offers a rapid
      approach for studying the molecular requirements for plant virus "self-assembly"
      in vivo. Transcription of a full-length cDNA clone of TMV RNA also resulted in
      high levels of CP expression and assembly of sufficient intact genomic RNA to
      initiate virus infection of susceptible tobacco plants.

PMID- 7518275
TI  - Enhanced tenascin immunoreactivity in leukoplakia and squamous cell carcinoma of
      the oral cavity: an immunohistochemical study.
AB  - Tenascin is an extracellular matrix glycoprotein that shows a site restricted
      expression especially in areas of cell proliferation, cell motility, and tissue
      modeling at the epithelial-mesenchymal junction during embryogenesis. Tissue
      specimens obtained from surgery and/or biopsy for oral leukoplakia (n = 22) and
      squamous cells carcinoma (n = 36) were examined for the presence of tenascin by
      using monoclonal antibody. In normal tissue specimens (n = 5), tenascin
      immunoreaction appeared as a linear continuous lining at the immediate vicinity
      of basement membrane (n = 3). Hyperplastic epithelia in leuoplakia showed a
      distinct increase in tenascin immunoreactivity in the submucosa correlating with
      the degree of hyperplasis and/or dysplasia. In squamous cell carcinoma (SCC), the
      reactivity was most intense extending deeply into the underlying stroma with
      marked reaction around large tumour cell nests and the infiltrating tumour
      margin. The connective tissue stroma, however, in undifferentiated carcinoma
      showed traces of immunoreactivity. Positive immunoreactivity was seen around
      metastatic squamous cell carcinoma masses in regional lymph nodes. The stromal
      tissues infiltrated by inflammatory cells were usually unreactive while those
      with desmoplastic changes were positive for tenascin. The authors conclude that
      an enhanced expression of tenascin may play an important role during active
      phases of tumour cell proliferation and stromal changes in the premalignant and
      malignant lesions of the oral mucosa.

PMID- 7518276
TI  - Exogenous zinc ion is required for inhibitory activity of botulinum neurotoxin C1
      against norepinephrine release and its endopeptidase activity toward substance P.
AB  - Botulinum neurotoxin C1 inhibited Ca(2+)-evoked norepinephrine secretion from
      digitonin-permeabilized PC12 cells. The inhibition by the neurotoxin was
      dependent on the presence of Zn2+ added exogenously. This zinc-dependent
      inhibition was neutralized by monoclonal antibodies that recognize the sites
      close to the putative zinc-binding motif in the light chain. The neurotoxin was
      found to have an endopeptidase activity toward small peptide, substance P. The
      presence of exogenous Zn2+ was also indispensable to the full expression of this
      endopeptidase activity. Thus both the inhibition of neurotransmitter release by
      the C1 neurotoxin and its endopeptidase activity are dependent on exogenous Zn2+,
      which suggests a strong link between the two activities.

PMID- 7518277
TI  - Epitope mapping of cytochrome P450 2B4 by peptide scanning.
AB  - Overlapping hexapeptides covering the whole sequence of the cytochrome P450 2B4
      have been synthesized on the solid supports and tested by ELISA using the
      polyclonal antiserum against cytochrome 2B4. 70 hexapeptide fragments have been
      found to interact specifically with the antiserum, i.e. to possess antigenic
      activity. The mapped linear epitopes occupy about 43% of the whole sequence of
      2B4. They presumably form clusters in the regions of No. 60-150, 210-300, 390-430
      and 465-486 amino acid residues. The use of cytochrome P450 DataBase has allowed
      to classify the revealed antigenic determinants into absolutely specific for 2B4,
      specific only for 2B4 and 2B5, characteristic for 2B subfamily and widely
      distributed in family 2.

PMID- 7518278
TI  - Effects of base analog substitutions in the sequence, CCGG, on the cleavage and
      methylation reactions of HpaII and MspI endonucleases and their cognate
      methylases.
AB  - HpaII endonuclease, HpaII methylase, MspI endonuclease, and MspI methylase were
      used to investigate their specific interactions with the common recognition
      sequence, CCGG. Six derivatives of the oligonucleotide, AGCCCGGGCT, containing a
      variety of single base analog substitutions within the tetrameric recognition
      core were synthesized. Steady state kinetic values for the reactions of all 4
      enzymes with these oligonucleotide substrates were obtained. Our data suggest
      that there are close contacts between the C5 positions of both cytosine residues
      and the enzymes except that MspI endonuclease can accommodate a methyl group at
      the C5 position of the second cytosine residue. The data also showed that minor
      groove interactions between the 2-amino group of both G residues and the HpaII or
      MspI endonuclease were essential for activity. However, these interactions were
      not essential for methylase activity except that the oligonucleotide substituted
      with inosine nucleotide at the first G position did not react with MspI
      methylase.

PMID- 7518279
TI  - RNA present in post-ribosomal supernatants makes ribosomes susceptible to
      inactivation by gelonin and alpha-sarcin.
AB  - The remarkable resistance of isolated ribosomes to gelonin is overcome by
      cofactors present in post-ribosomal supernatants. In rat liver post-ribosomal
      supernatant RNA is the cofactor responsible of the sensitization of ribosomes.
      Isolated RNA, which consists mostly of deacylated tRNA, accounts for less than 10
      per cent of the activity of the original supernatant. The activity of the
      supernatant is completely destroyed by micrococcal nuclease and RNAase A and also
      by proteinase K, suggesting that some protein enhances the effect of RNA. RNA has
      a role also in the sensitization of ribosomes to alpha-sarcin, an RNAase which
      inactivates ribosomes by hydrolyzing a single phosphodiester bond in the same
      region of 28S rRNA which is the target of the N-glycosidase activity of gelonin.

PMID- 7518281
TI  - Cat and dog: higher center of micturition.
AB  - The nervous control of micturition in the pontine level was studied using cats
      and dogs as research specimens. Two techniques for this purpose were employed:
      (1) electrical and chemical stimulations research and (2) nerve tracing research.
      This investigation suggests that two distinct pontine centers exist, the commonly
      known pontine micturition center (PMC) which is responsible for urine emptying,
      and a second, very important pontine center which functions as the urine storage
      facilitator (PUSFC). The PMC, which triggers bladder contractions and
      micturition, is located in the nucleus locus coerleus alpha (LCa). The second
      center (PUSFC) is located in the nucleus locus subcoerleus (LSC). Micturition is
      controlled by close coordinate operation of both centers in the pontine level.

PMID- 7518282
TI  - Inhibition of chromosome condensation.

PMID- 7518283
TI  - Analysis of chromosomes with restriction endonucleases and DNase
      hypersensitivity.

PMID- 7518284
TI  - Bivariate chromosome analysis using a commercial flow cytometer.

PMID- 7518280
TI  - New targets for pyrimidine antimetabolites in the treatment of solid tumours. 1:
      Thymidylate synthase.
AB  - Thymidylate synthase forms the target for anticancer therapy with
      fluoropyrimidines. Anticancer activity can be increased by the use of different
      modulators of fluoropyrimidine metabolism, which lead to an enhanced inhibition
      of thymidylate synthase. In vitro and in vivo studies with fluoropyrimidines and
      two of these modulators, folinic acid (leucovorin) and interferon, are
      summarized. The promise of these preclinical results is reflected by the response
      data of several clinical trials. The biochemical effects of these modulators are
      described and illustrated by the fluoropyrimidine-mediated inhibition of
      thymidylate synthase in tumour samples, which is clearly enhanced by folinic
      acid. The regulation of thymidylate synthase synthesis may also be crucial for
      total blockade of thymidylate synthase activity. This regulation may be
      influenced by interferon-gamma. Although the addition of modulators increases the
      activity of fluoropyrimidines at the level of thymidylate synthase, most solid
      tumours, especially colorectal carcinomas, are resistant to these combinations.
      For this reason, new, more potent inhibitors of thymidylate synthase have been
      developed, the antifolates. Preclinical data show that some of these compounds
      have good antitumour activity, but they still have to prove their value in the
      clinic. These two approaches, the use of modulators and new compounds, have shown
      activity preclinically and the extension of these findings to clinical studies
      stresses the importance of thymidylate synthase as a target in fluoropyrimidine
      therapy of solid tumours.

PMID- 7518287
TI  - Chromosome banding and identification absorption staining.

PMID- 7518286
TI  - Immortalized cell lines. Chromosome preparation and banding.

PMID- 7518285
TI  - Chromosome sorting by flow cytometry. Production of DNA libraries and gene
      mapping.

PMID- 7518288
TI  - Chromosome banding and identification. Fluorescence.

PMID- 7518289
TI  - Chromosome banding. Stain combinations for specific regions.

PMID- 7518290
TI  - Hospital roommates: an interview with a terminally ill patient.

PMID- 7518291
TI  - Immunoelectron microscopic observations on Leu-7 positive cells in virus-related
      chronic liver diseases.
AB  - We investigated the liver biopsies of 78 patients with hepatitis virus-related
      chronic liver diseases (B type; 14 patients, C type; 64 patients) by
      immunoelectron microscopy with the Leu-7 monoclonal antibody in order to
      determine the association of NK/K cells in virus-related chronic liver diseases.
      Most Leu-7 positive cells in the liver had the Pit cell morphology but a few Pit
      cells were Leu-7 negative. A few Leu-7 positive cells had neither Pit cell nor
      typical T cell morphology. No ultrastructural difference was observed in Leu-7
      positive cells between hepatitis B virus- and hepatitis C virus-related chronic
      liver diseases. Regardless of virus type and hepatitis activity, the fine
      morphology of extravascular Leu-7 positive cells differed considerably from
      intravascular cells. Leu-7 positive cells were regularly seen in the cellular
      infiltrates but the ratio of Leu-7 positive cells/whole infiltrates was low.
      There was no correlation between the inflammatory activity of the disease and the
      level of Leu-7 positive cell infiltration. A virus aetiology (hepatitis-C or
      hepatitis-B) did not affect Leu-7 positive cell infiltration. We conclude that NK
      cells play only a small role in the pathogenesis of hepatitis B virus or
      hepatitis C virus-related hepatocytolysis, during the chronic stage.

PMID- 7518292
TI  - Tenascin expression in normal human adult skin and skin appendage tumours.
AB  - The expression and distribution of tenascin, an extracellular matrix
      glycoprotein, was investigated immunohistochemically using an anti-human tenascin
      monoclonal antibody (RCB 1) in formalin-fixed paraffin-embedded tissues obtained
      from 79 patients with skin appendage tumours, and compared with adjacent normal
      skin. Tissue specimens were pretreated with actinase and processed by the
      labelled streptavidin-biotin method. In normal skin, tenascin immunoreactivity
      was consistently found around the ductal portion of the sweat glands, around the
      lower part of the hair follicle and hair bulbs, and around or within blood
      vessels. Immunoreactivity was also observed variably around secretory coils of
      the sweat glands, and below the epidermis. No immunoreactivity was seen around
      the sebaceous glands. Tumours originating from sweat glands and hair follicles
      expressed tenascin around the tumour cells nests, while sebaceous gland tumours
      were immunonegative. Thus, tenascin expression in skin appendage tumours
      generally resembled that in corresponding normal tissue.

PMID- 7518293
TI  - Frequent expression of 75 kDa nerve growth factor receptor and phosphotyrosine in
      human peripheral nerve tumours: an immunohistochemical study on paraffin-embedded
      tissues.
AB  - One hundred and three benign, and 10 malignant peripheral nerve tumours were
      examined immunohistochemically for expression of 75 kDa nerve growth factor
      receptor (NGFR). In benign tumours NGFR was demonstrated at 61% in neurinoma, 71%
      in neurofibroma, 93% in neurofibromatosis and 90% in traumatic neuroma. Malignant
      neurogenic tumours were 100% positive for NGFR. Phosphotyrosine-immunoreactivity
      was detected in 76% of NGFR-positive tumours but the frequency of immunostained
      tumour cells was low. These results suggest that both benign and malignant
      peripheral nerve tumours express 75 kDa NGFR. The receptor seems to serve as
      growth signal transduction of the tumour cells in terms of phosphorylation of the
      tyrosine residue of the receptor or the target protein of the NGFR protein
      tyrosine kinase.

PMID- 7518294
TI  - Inhibition of excitatory non-adrenergic non-cholinergic bronchoconstriction in
      guinea-pig airways in vitro by activation of an atypical 5-HT receptor.
AB  - 1. The effect of 5-hydroxytryptamine (5-HT) was studied on excitatory neurally
      mediated non-adrenergic non-cholinergic (NANC) contractions evoked by electrical
      field stimulation (EFS) in guinea-pig isolated bronchi. 2. 5-HT (0.1-100 microM)
      produced a concentration-dependent inhibition of the excitatory NANC response
      with 50.9 +/- 5.0% (n = 5, P < 0.01) inhibition at 100 microM. This inhibition
      was not significantly affected by the 5-HT2 antagonist, ketanserin (1 microM)
      when inhibitions (+/- ketanserin) at each concentration of 5-HT were compared by
      unpaired t tests; however, this concentration appeared to produce a leftward
      shift (approximately 10 fold) of the 5-HT concentration-inhibition curve.
      Ketanserin (1 microM) was effective in blocking bronchoconstriction evoked by
      activation of 5-HT2A receptors on airway smooth muscle. In the presence of
      ketanserin (1 microM) 5-HT (100 microM) evoked an inhibition of 57.4 +/- 5.9% (n
      = 5, P < 0.01) with an EC50 of 0.57 microM. 3. Inhibition evoked by 5-HT (0.1-100
      microM) was unaffected by the alpha-adrenoceptor antagonist phentolamine (1
      microM), the beta 2-adrenoceptor antagonist, ICI 118551 (0.1 microM), the 5
      HT1A/B antagonist, cyanopindolol (1 microM) or the 5-HT3/4 antagonist, ICS 205
      930 (1 microM). 4. Methiothepin (0.1 microM) produced an insurmountable
      inhibition of the effect of 5-HT (0.1-100 microM), reducing the maximum
      inhibition produced by 5-HT (100 microM) to 30.2 +/- 5.0% (n = 5, P < 0.001) and
      suggesting a non-competitive antagonism. Methiothepin inhibited the effect of 5
      HT (10 microM) in a concentration-dependent manner with an IC50 of 81 nM. 5.
      Selective 5-HT receptor agonists were also tested on excitatory NANC responses. 5
      Carboxamidotryptamine (5-CT, 0.1-100 MicroM) was the most potent, producing a
      concentration-dependent inhibition with an EC50 of 0.13 MicroM. Calculation of
      approximate IC25 values (concentration of the agonist required to give a 25%
      inhibition of the excitatory NANC response) gave a rank order of potency 5-CT > 5
      HT> > 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) >alpha-methyl-5
      hydroxytryptamine (alpha-Me-5HT). Sumatriptan, 5-methoxytryptamine (5-MeOT) and 2
      methyl-5-hydroxytryptamine (2-Me-5HT) were essentially inactive with IC25> 100
      MicroM.6. 5-HT (10 microM) did not significantly affect contractile responses to
      exogenously applied substance P(1 nM-10 Microm).7. The effect of 5-HT was
      unchanged after incubation with the nitric oxide (NO) synthase inhibitor L-NG
      nitroarginine methyl ester (L-NAME, 100 Microm). However, pretreatment with
      charybdotoxin (ChTX,0.1-30 nM), a blocker of the large conductance Ca2+-activated
      K+channel (K+ca), produced a concentration-dependent inhibition of the effect of
      5-HT (10 MicroM).8. 5-HT evokes a concentration-dependent inhibition of e-NANC
      bronchoconstriction in guinea-pig isolated bronchi but does not affect cumulative
      concentration-dependent contractile responses to substance P, suggesting that
      inhibition is via a prejunctional receptor. Effects of selective antagonists and
      agonists suggest that an atypical 5-HT receptor mediates this inhibition. The
      inhibitory effect of 5-HT does not involve the production of NO, but may involve
      the opening a ChTX-sensitive K+ca channel.These data suggest that an atypical 5
      HT receptor inhibits the release of neuropeptides from sensory C fibres and may
      act as other inhibitory neuromodulators via the opening of a common K'channel.

PMID- 7518295
TI  - Functional effects and ligand binding of chimeric galanin-neuropeptide Y (NPY)
      peptides on NPY and galanin receptor types.
AB  - 1. The effects and binding characteristics of a series of chimeric galanin
      neuropeptide Y (NPY) peptides were examined in various preparations known to
      contain a predominant population of either Y1 or Y2 receptors for NPY or galanin
      receptors. 2. NPY suppressed the electrically stimulated twitches of the rat vas
      deferens (Y2 receptors), while galanin enhanced the electrically stimulated
      twitches. The galanin-NPY peptides M 32 (galanin(1-13)-NPY(25-36)), M69A
      (galanin(1-13)-Lys-[epsilon NH-Gly-NPY(4-1)]NPY(25-36)) and M88 (galanin(1-12)
      Ala-NPY(25-36)) evoked a concentration-dependent suppression of the electrically
      stimulated twitches. These chimeric peptides were about equipotent with NPY,
      while NPY (13-36) was about five times less potent than NPY itself. Also a
      stochiometric combination of the N- and C-terminal fragments NPY (1-24)NH2 and
      NPY (25-36) (each at 1 microM) was inactive in vas deferens. M120 (galanin (1-13)
      NPY(14-36) (1 microM) did not affect the NPY-mediated suppression of the
      stimulated twitches. 3. NPY evoked a concentration-dependent contraction in the
      guinea-pig isolated caval vein (Y1 receptors), while galanin (< or = 1 microM)
      was inactive. M32, M69A and M88 induced a slight contraction at very high
      concentrations only (> or = 0.3 M), while M120 was inactive at 1 microM. None of
      the four chimeric peptides affected the contraction evoked by NPY. 4. Since the
      number of NPY receptors in the rat vas deferens and guinea-pig caval vein were
      too low,the affinities of the galanin-NPY peptides for [3H]-NPY binding sites
      were examined in membranes from rat brain areas known to contain predominant
      populations of Y1 receptors (cerebral cortex) and Y2 receptors (hippocampus),
      respectively. The chimeric peptides M32, M69A, M88, M120 and NPY (13-36)all had
      higher affinities for hippocampal binding sites than for cerebral cortical
      binding sites. These peptides were 90-440 times less potent than NPY at cerebral
      cortical binding sites and 15-125 times less potent than NPY at hippocampal
      binding sites. The most selective chimeric peptide was M32, which had a 20 fold
      higher affinity for hippocampal than for cerebral cortical binding sites.5. At
      hypothalamic [125I]-galanin binding sites M32, M88 and M69A were equipotent with
      galanin,while M120 was about 10 times less potent than galanin. M32, M88 and
      M69A, like galanin contracted the rat isolated jejunum.6. The N-terminal portion
      (1-12) of galanin seems to permit a steric conformation of the attached NPY (25
      36) part of the chimeric galanin-NPY peptides, which results in a facilitated Y2
      but not Y1.receptor recognition and activation. None of the galanin-NPY peptides
      appeared to act as antagonists at either type of NPY receptor, probably due to
      their low affinity. Instead, they displayed a very high affinity for hypothalamic
      galanin receptors and probably act as galanin agonists in the rat jejunum.

PMID- 7518296
TI  - IgE-receptor activated chloride uptake in relation to histamine secretion from
      rat mast cells.
AB  - 1. Antigen-stimulated histamine secretion from rat peritoneal mast cells was
      inhibited when extracellular chloride was replaced by either isethionate or
      gluconate anions, but the histamine release still remained quite substantial. 2.
      Rat peritoneal mast cells take up 36Cl and the uptake reaches a steady state
      after 60 min incubation with the isotope. At steady state, the intracellular
      chloride level in the cells was calculated to be 29 +/- 11.5 mM. 3. The chloride
      uptake in mast cells was exponential with a rate constant of 0.036 min-1 in
      resting cells. When the cells were stimulated with antigen, and rate constant for
      chloride uptake increased to 0.90 min-1: an increase of 25 fold. Under identical
      experimental conditions histamine release increased 3 fold. 4. The rate of
      chloride uptake in either resting cells or in antigen-stimulated cells was not
      changed when the extracellular medium was nominally calcium-free but histamine
      release was almost completely inhibited in the absence of extracellular calcium.
      5. The putative chloride channel blocker DIDS (4,4'-diisothiocyanatostilbene-2,2'
      disulphonic acid) 0.3 to 30 microM, produced a concentration-related inhibition
      of antigen-stimulated histamine secretion but DIDS (30 microM) did not inhibit
      the antigen-stimulated increase of chloride uptake. 6. The cyclic AMP analogue,
      dibutyryl cyclic AMP (1 mM) produced a delayed increase in chloride uptake in
      resting mast cells but neither dibutyryl cyclic AMP nor 8-bromo cyclic AMP per se
      induced any histamine secretion. 7. Ouabain (1 mM) which inhibits the Na+/K+
      ATPase in rat peritoneal mast cells, failed to affect the uptake of chloride in
      resting mast cells. 8. The Na/K/2C1-cotransport inhibitor, furosemide (0.7 mM),
      slowed the unstimulated chloride uptake in resting mast cells and abolished the
      increased antigen-induced chloride uptake when added together with antigen. In
      contrast, spontaneous and antigen-induced histamine release were unaffected by
      the presence of furosemide. However, when furosemide was added to the cell
      suspension 5 min before stimulation, furosemide was without effect on the antigen
      induced chloride uptake.9. In addition to the chloride uptake mediated by
      chloride channels which may be related to the mechanism of histamine secretion,
      crosslinking of the high affinity membrane receptors for IgE is followed by a
      fast chloride uptake that is likely to occur through a furosemide-sensitive
      Na/K/2C1-cotransporter.

PMID- 7518297
TI  - Effect of anti-fungal imidazoles on mRNA levels and enzyme activity of inducible
      nitric oxide synthase.
AB  - 1. Experiments were performed to examine the effects of anti-fungal imidazole
      compounds (clotrimazole, econazole and miconazole) on the induction of nitric
      oxide (NO) synthase and subsequent production of NO in the cultured murine
      monocyte/macrophage cell line J774 using a specific cDNA probe for inducible NO
      synthase mRNA and by monitoring nitrite production. 2. Stimulation of J774 cells
      with lipopolysaccharide (LPS, 10 micrograms ml-1) resulted in the induction of NO
      synthase activity as determined by nitrite accumulation in the culture medium (48
      +/- 3 nmol per 10(6) cells over 24 h). Production of nitrite was inhibited by co
      incubation of cells with LPS (10 micrograms ml-1) and either dexamethasone (10
      microM) or NG-monomethyl-L-arginine (L-NMMA; 0.1 mM), however, only L-NMMA was an
      effective inhibitor of nitrite production when added after induction of NO
      synthase had occurred. 3. Co-incubation of J774 cells with LPS (10 micrograms ml
      1) and either clotrimazole, econazole or miconazole (1-10 microM) resulted in a
      concentration-dependent inhibition of nitrite production over the subsequent 24 h
      without any evidence for a cytotoxic effect. However, addition of these
      imidazoles after induction of NO synthase did not inhibit nitrite production. 4.
      Messenger RNA for inducible NO synthase was not detected in unstimulated J774
      cells. Treatment with LPS (10 micrograms ml-1) for 4 h resulted in significant
      expression of mRNA for inducible NO synthase which was not altered in the
      presence of econazole (10 microM) but was reduced significantly by dexamethasone
      (10 microM). 5. These results demonstrate that anti-fungal imidazoles inhibit the
      production of nitric oxide by cultured J774 cells by a mechanism which appears to
      differ from that of dexamethasone and substrate type inhibitors of NO synthase.
      Furthermore, the presence of mRNA for NO synthase does not indicate the presence
      of functionally active NO synthase.

PMID- 7518298
TI  - Time-dependent enhancement or inhibition of endotoxin-induced vascular injury in
      rat intestine by nitric oxide synthase inhibitors.
AB  - 1. The effects of the nitric oxide (NO) synthase inhibitors, NG-nitro-L-arginine
      methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), on the vascular
      damage induced by the endotoxin, E. coli lipopolysaccharide (LPS), in the ileum
      and colon were investigated in the conscious rat over a 5 h period. 2.
      Administration of LPS (3 mg kg-1, i.v.) increased ileal and colonic vascular
      injury after a lag period of 2 h, as determined by the leakage of radiolabelled
      albumin. 3. Administration of L-NAME (1-5 mg kg-1, s.c.) concurrently with LPS,
      produced a dose-dependent increase in vascular albumin leakage in the intestinal
      tissues, when determined over a 5 h period. Vascular albumin leakage with LPS and
      L-NAME (5 mg kg-1) was substantially increased after 1 h, reached maximal levels
      3 h after administration, and then slowly declined. 4. L-NMMA (50 mg kg-1, s.c.),
      likewise elevated intestinal albumin leakage when administered concurrently with
      LPS, but this reached maximal levels after 1 h and rapidly declined over the
      subsequent 2 h. 5. In control rats, in the absence of LPS challenge, neither L
      NAME (5 mg kg-1, s.c.) nor L-NMMA (50 mg kg-1, s.c.) increased intestinal
      vascular leakage of albumin over a 5 h period. 6. By contrast, when L-NAME (1-5
      mg kg-1, s.c.) or L-NMMA (12.5-50 mg kg-1, s.c.) was injected 3 h after LPS, a
      dose-dependent reduction in the LPS-provoked vascular albumin leakage was
      observed. 7 Pretreatment with L-arginine (300 mg kg-1, s.c.) 15 min prior to the
      NO synthase inhibitors, reversed either the potentiation or the inhibition by L
      NAME (5 mg kg-1, s.c.) or L-NMMA (50 mg kg-1, s.c.) of the LPS-induced intestinal
      vascular damage.8. These findings indicate that initial suppression of the
      constitutive NO synthase by L-NAME orL-NMMA following challenge with LPS
      aggravates the acute vascular injury in the ileum and colon,suggesting a
      defensive role of NO. By contrast, the delayed administration of NO synthase
      inhibitors, ata time of known expression of the inducible NO synthase, provides
      protection against the subsequent damage to the intestinal vasculature.

PMID- 7518299
TI  - Investigation of the specificity of FK 888 as a tachykinin NK1 receptor
      antagonist.
AB  - 1. A recently described peptide tachykinin (NK1) receptor antagonist, FK 888, was
      found to inhibit the electrically-evoked, tachykinin-mediated contractile
      responses of the rabbit iris sphincter in a concentration-dependent manner; the
      pIC50 value was 6.6 +/- 0.08. 2. Contractions induced by a selective NK1 receptor
      agonist, [Sar9,Met(O2)11]substance P, were inhibited competitively by FK 888; the
      pKB value was 7.1. 3. FK 888 (1 nM-100 microM) was without effect on the
      electrically-evoked, cholinergic response of the rabbit iris sphincter and the
      electrically-evoked, sympathetic response of the guinea-pig vas deferens. The
      contractions of the rabbit iris sphincter, induced by either carbachol (10 nM-30
      microM) or noradrenaline (0.1-100 microM), were not affected by 10 microM FK 888.
      4. FK 888 (1-30 microM) did not induce histamine release from rat peritoneal mast
      cells. 5. FK 888 (33 and 333 microM) was without effect on the electrically
      evoked action potentials of the frog sciatic nerve. Thus, FK 888 is a moderately
      high affinity and selective tachykinin (NK1) receptor antagonist.

PMID- 7518300
TI  - Expression of nitric oxide synthase in rat glomerular mesangial cells mediated by
      cyclic AMP.
AB  - 1. Treatment of rat mesangial cells with interleukin 1 beta (IL-1 beta) or tumour
      necrosis factor alpha (TNF alpha) has been shown to induce a macrophage-type of
      nitric oxide (NO) synthase. Here we report that adenosine 3':5'-cyclic
      monophosphate (cyclic AMP) is another mediator that triggers induction of NO
      synthase in mesangial cells. 2. Incubation of mesangial cells with the beta
      adrenoceptor agonist, salbutamol, forskolin or cholera toxin, which all activate
      adenylate cyclase and increase intracellular cyclic AMP concentration, increased
      nitrite formation in a dose-dependent manner. Likewise, the addition of the
      membrane-permeable cyclic AMP analogue, N6, 0-2'-dibutyryladenosine 3',5'
      phosphate (Bt2 cyclic AMP) or the phosphodiesterase inhibitor, 3-isobutyl-1
      methylxanthine enhanced NO synthase activity in a dose-dependent manner. 3. There
      was a lag period of about 8 h before a significantly enhanced secretion of
      nitrite could be detected upon exposure of cells to forskolin and for maximal
      stimulation, forskolin had to be present during the whole incubation period. 4.
      Treatment of mesangial cells with actinomycin D, cycloheximide or dexamethasone
      completely suppressed forskolin-stimulated NO-synthase activity, thus
      demonstrating that transcription and protein synthesis are necessary for nitrite
      formation. 5. Bt2 cyclic AMP, the most potent inducer of nitrite production,
      increased NO synthase mRNA levels in mesangial cells in a time- and dose
      dependent fashion. Dexamethasone completely inhibited the increase of NO synthase
      mRNA in response to Bt2 cyclic AMP. 6. Combination of Bt2 cyclic AMP and IL-1
      beta or TNF alpha revealed a strong synergy in terms of nitrite formation. Time
      course studies indicated that cyclic AMP needed to be increased during the whole
      period of IL-1 Beta stimulation for maximal nitrite production.7. These
      observations suggest that cyclic AMP controls NO synthase expression in mesangial
      cells.Furthermore, the signalling cascades triggered by IL-1 Beta and TNF alpha
      synergize with the cyclic AMP pathway to stimulate NO synthase activity.

PMID- 7518301
TI  - Comparison of two new inhibitors of catechol O-methylation on striatal dopamine
      metabolism: a microdialysis study in rats.
AB  - 1. Effects of two new inhibitors of catechol O-methylation (CGP 28014 and
      entacapone; 30 mg kg-1, i.p.) were compared by means of brain microdialysis in
      rats treated with L-3,4-dihydroxyphenylalanine (L-dopa)/carbidopa (50/50 mg kg-1,
      i.p., respectively) or saline. 2. In saline-treated rats, CGP 28014 maximally
      (max) increased striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC)
      effluxes by 41% and 49%, respectively, whereas homovanillic acid (HVA) levels
      were decreased by 71%. 3. In the presence of L-dopa/carbidopa, a peripherally
      active inhibitor of catechol O-methyltransferase (COMT) entacapone had a short
      lasting increasing effect on L-dopa efflux. Compared to the effects of L
      dopa/carbidopa alone 3-O-methyldopa (3-OMD) levels were effectively reduced (max
      79%) by entacapone, but not by CGP 28014. 4. Entacapone, in contrast to CGP
      28014, increased striatal dopamine efflux (max 492% of that after L
      dopa/carbidopa alone). Also DOPAC levels were increased by entacapone (255% at
      180 min), but not significantly by CGP 28014 (159% at 180 min). 5. Both compounds
      initially decreased HVA efflux. The effect of CGP 18014 was longer-lasting. By
      the end of the measurement, entacapone even increased HVA levels (max 259%). 6.
      Our results demonstrate that entacapone is a peripheral COMT inhibitor and
      support the view that CGP 18014 is mainly a centrally acting inhibitor of O
      methylation.

PMID- 7518303
TI  - Differences in the effects of NK1-receptor antagonists, (+/-)-CP 96,345 and CP
      99,994, on agonist-induced responses in guinea-pig trachea.
AB  - 1. The effects of the NK1-receptor antagonists, (+/-)-CP 96,345 and CP 99,994, on
      NK1-agonist evoked contractions were compared in isolated rings of guinea-pig
      tracheal smooth muscle. 2. (+/-)-CP 96,345 and CP 99,994 were similarly effective
      in antagonizing responses evoked by septide, whereas CP 99,994 was more effective
      than (+/-)-CP 96,345 in inhibiting responses evoked by [Sar9Met11(O2)] substance
      P. 3. These results suggest that responses to septide and [Sar9Met11(O2)]
      substance P may be operated via different populations of NK1-receptors.

PMID- 7518302
TI  - Comparison of tachykinin NK1 and NK2 receptors in the circular muscle of the
      guinea-pig ileum and proximal colon.
AB  - 1. The aim of this study was the pharmacological characterization of tachykinin
      NK1 and NK2 receptors mediating contraction in the circular muscle of the guinea
      pig ileum and proximal colon. The action of substance P (SP), neurokinin A (NKA)
      and of the synthetic agonists [Sar9]SP sulphone, [Glp6,Pro9]SP(6-11) (septide)
      and [beta Ala8]NKA(4-10) was investigated. The affinities of various peptide and
      nonpeptide antagonists for the NK1 and NK2 receptor was estimated by use of
      receptor selective agonists. 2. The natural agonists, SP and NKA, produced
      concentration-dependent contraction in both preparations. EC50 values were 100 pM
      and 5 nM for SP, 1.2 nM and 19 nM for NKA in the ileum and colon, respectively.
      The action of SP and NKA was not significantly modified by peptidase inhibitors
      (bestatin, captopril and thiorphan, 1 microM each). 3. Synthetic NK1 and NK2
      receptor agonists produced concentration-dependent contraction of the circular
      muscle of the ileum and proximal colon. EC50 values were 83 pM, 36 pM and 10 nM
      in the ileum, 8 nM, 0.7 nM and 12 nM in the colon for [Sar9]SP sulphone, septide
      and [beta Ala8]NKA-(4-10), respectively. The pseudopeptide derivative of NKA(4
      10), MDL 28,564 behaved as a full or near-to-full agonist in both preparations,
      its EC50s being 474 nM and 55 nM in the ileum and colon, respectively. 4.
      Nifedipine (1 microM) abolished the response to septide and [Sar9]SP sulphone in
      the ileum and produced a rightward shift and large depression of the response in
      the colon. The response to [beta Ala8]NKA(4-10) was abolished in the ileum and
      largely unaffected in the colon. 5. The NK1 receptor antagonists, (+/-)-CP 96,34,
      FK 888 and GR 82,334 competitively antagonized the response to septide and
      [Sar9]SP sulphone in both preparations without affecting that to [beta Ala8]NKA(4
      10). In general, the NK1 receptor antagonists were significantly more potent
      toward septide than [Sar9]SP sulphone in both preparations. 6. The NK2 receptor
      antagonists, GR 94,800 and SR 48,968 selectively antagonized the response to
      [beta Ala8]NKA(4-10) without affecting that to [Sar9]SP sulphone or septide in
      the ileum and colon. SR 48,968 produced noncompetitive antagonism of the response
      to the NK2 receptor agonist in the ileum and competitive antagonism in the colon.
      7. MEN 10,376 and the cyclic pseudopeptide MEN 10,573 antagonized in a
      competitive manner the response to [beta Ala8]NKA(4-10) in the ileum and colon.
      While MEN 10,573 was equipotent in both preparations, MEN 10,376 was
      significantly more potent in the colon than in the ileum. MEN 10,376was also
      effective against septide in both preparations, without affecting the response to
      [Sar9] SP sulphone. MEN 10,573 antagonized the response to [Sar9]SP sulphone and
      septide in both preparations,pKB values against septide being intermediate, and
      significantly different from, those measured against[Beta Ala 8]NKA(4-10) and
      [Sa9]lSP sulphone.8. These findings show that tachykinin NK1 and NK2 receptors
      mediate contraction of the circular muscle of the guinea-pig ileum and colon. In
      both preparations NK1 receptor antagonists display higher apparent affinity when
      tested against septide than [Sar9]SP sulphone. These findings are compatible with
      the proposed existence of NK1 receptor subtypes in guinea-pig, although
      alternative explanations (e.g.agonist binding to different epitopes of the same
      receptor protein) cannot be excluded at present.Furthermore, an intraspecies
      heterogeneity of the NK2 receptor in the circular muscle of the guinea-pig ileum
      and colon is suggested.

PMID- 7518304
TI  - Cardiovascular and behavioural effects of centrally administered tachykinins in
      the rat: characterization of receptors with selective antagonists.
AB  - 1. The effects of intracerebroventricular (i.c.v.) injection of selective and
      potent NK1 (RP 67580), NK2 (SR 48968) and NK3 (R 486, [Trp7, beta-Ala8]NKA(4-10))
      receptor antagonists were assessed on the cardiovascular and behavioural
      responses elicited by the i.c.v. injection of substance P (SP), neurokinin A
      (NKA) or [MePhe7]neurokinin B ([MePhe7]NKB) in the conscious freely moving rat.
      2. SP, NKA and [MePhe7]NKB (5-650 pmol) evoked dose-dependent increases in mean
      arterial blood pressure (MAP) and heart rate (HR) with the rank order of potency
      SP > NKA > [MePhe7]NKB. The cardiovascular responses were accompanied by
      excessive face washing, grooming and wet dog shakes. 3. The cardiovascular
      effects and face washing behaviour induced by SP (25 pmol) were significantly
      reduced by the pre-injection (i.c.v., 5 min earlier) of RP 67580 (6.5 nmol).
      However, this antagonist failed to affect the central effects of 25 pmol NKA or
      [MePhe7]NKB. 4. The cardiovascular and behavioural responses (except for wet dog
      shakes) elicited by NKA (25 pmol) were significantly reduced by 6.5 nmol SR
      48968. However, the latter antagonist had no effect on the SP or [MePhe7]NKB
      mediated responses. 5. Both cardiovascular and behavioural effects produced by
      either SP or NKA (25 pmol) were completely abolished when rats were pretreated
      with a combination of RP 67580 (6.5 nmol) and SR 48968 (6.5 nmol), yet this
      combination of antagonists failed to modify the central effects of [MePhe7]NKB.
      6. R 486 (6.5 nmol) inhibited the cardiovascular effects as well as wet dog
      shakes produced by [MePhe7]NKB, but it was inactive against the responses induced
      by either SP or NKA. 7. None of the tachykinin receptor antagonists or agonists
      caused motor impairment or respiratory distress. All antagonists blocked in a
      reversible manner and were devoid of intrinsic activity except R486 (6.5 nmol)
      which produced a transient increase of MAP and HR.8. These results suggest that
      the central effects of SP, NKA and [MePhe7]NKB are primarily mediated by central
      NK1, NK2 and NK3 receptors, respectively. However, a minor activation of NK2
      receptors bySP and NK1 receptors by NKA was seen during blockade of both
      receptors. This study therefore supports the existence of functional NK1, NK2 and
      NK3 receptors in the adult rat brain.

PMID- 7518305
TI  - Cardiovascular and behavioural effects of centrally administered neuropeptide K
      in the rat: receptor characterization.
AB  - 1. The cardiovascular and behavioural responses to intracerebroventricularly
      (i.c.v.) administered neuropeptide K (NPK) were studied in conscious rats. The
      central effects of NPK were characterized by pretreatment (i.c.v.) with selective
      antagonists for the NK1 ((+/-)-CP 96345 and RP 67580), NK2 (SR 48968) and NK3 (R
      487) receptors. 2. NPK (10-65 pmol) induced tachycardia and dose-dependent
      increases of mean arterial blood pressure. The cardiovascular responses reached a
      maximum within 3 min post-injection and lasted for more than 1 h. Concurrently,
      NPK produced dose-dependent increases of face washing, head scratching, grooming,
      walking and wet dog shakes. 3. A desensitization of most of the behavioural
      responses (except head scratching) but not of the cardiovascular response was
      shown when two consecutive injections of 25 pmol NPK were given 24 h apart. 4.
      Both the cardiovascular and behavioural responses (except the head scratching) to
      25 pmol NPK were blocked by pre-administration (i.c.v.) of 6.5 nmol (+/-)-CP
      96345 or RP 67580 given 5 min earlier. No inhibition of NPK responses was
      observed when 6.5 nmol SR 48968 or R 487 were used in a similar study.
      Additionally, NPK effects were significantly reduced 24 h after the prior
      injection of (+/-)-CP 96345 but not of RP 67580. 5. These results support the
      involvement of NK1 receptors in the cardiovascular and behavioural effects of
      i.c.v. NPK. Thus, this peptide may play a putative role in central cardiovascular
      regulation as it is the most potent endogenous tachykinin described centrally, to
      date.

PMID- 7518306
TI  - The effect of nitric oxide synthase inhibition on the plasma fibrinolytic system
      in septic shock in rats.
AB  - 1. We have investigated the effect of pretreatment of rats with nitric oxide (NO)
      synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on the E. coli
      lipopolysaccharide (LPS)-induced changes in the plasma fibrinolytic system,
      platelet count, fibrinogen level, as well as in gross and microscopic
      pathophysiological changes indicative of disseminated intravascular coagulation
      (DIC) in rats. 2. E. coli LPS (6 mg kg-1, i.p.) produced a decrease in the levels
      of plasma fibrinogen and a drop in the blood platelet count 6 h after
      administration. The decrease in fibrinogen but not the drop in platelet count was
      reversed by pretreatment with L-NAME (30 mg kg-1, i.p., 24 h and 15 min before
      administration of LPS). 3. Pretreatment with L-NAME antagonized the LPS-induced
      activation of fibrinolysis as measured by changes in the euglobulin clot lysis
      time (ECLT) and enhanced the LPS-induced rise in the plasma level of plasminogen
      activator inhibitor (PAI). In animals pretreated with L-NAME there was also a
      marked reduction in the histological changes indicative of DIC. 4. We propose
      that L-NAME can act as a protective agent in LPS-induced DIC, and this protection
      is due to an increased generation of PAI following inhibition of NO synthase.

PMID- 7518307
TI  - Chloride secretion in response to guanylin in colonic epithelial from normal and
      transgenic cystic fibrosis mice.
AB  - 1. Guanylin, a 15 amino acid endogenous gut peptide, increased the short circuit
      current (SCC) in the epithelium of the mouse colon, but only when applied to the
      apical and not the basolateral surface. 2. By use of selective blockers of
      epithelial ion transport and modification of the bathing solution, it was
      concluded that guanylin increased electrogenic chloride secretion but also had a
      minor effect on electrogenic sodium absorption. In addition there were small
      residual currents which remained unresolved. 3. The threshold concentration of
      guanylin causing a SCC increase was less than 50 nM, but at concentrations 40
      times greater no indication of a maximally effective concentration was found. 4.
      Two guanylin isomers with the same amino acid sequence but with the disulphide
      bridges joined in an alternate fashion showed no activity. Thus only guanylin
      with the greatest structural homology to heat stable enterotoxin (STa) showed
      biological activity. 5. The action of guanylin was virtually eliminated in
      colonic epithelia from transgenic cystic fibrosis (CF) mice. As these animals
      lack the chloride channel coded by the CF gene sequence, it is likely that the
      final effector process in murine colonic epithelia involves the CFTR (cystic
      fibrosis transmembrane conductance regulator) chloride channel. 6. Opportunistic
      infections of the gut generating STa lead to diarrhoeal conditions via an action
      of the toxin on apical guanylin receptors. Thus, as discussed, the CF
      heterozygote may have a genetic advantage in this circumstance.

PMID- 7518308
TI  - Effect of potassium channel blockade and alpha 2-adrenoceptor activation on the
      release of nitric oxide from non-adrenergic non-cholinergic nerves.
AB  - 1. Using a superfusion bioassay cascade, we studied the effect of K+ channel
      blockers and alpha 2-adrenoceptor agents on the release of a transferable factor,
      previously characterized as nitric oxide (NO) or a nitric oxide-related substance
      (NO-R), in response to non-adrenergic non-cholinergic (NANC) nerve stimulation in
      the canine ileocolonic junction (ICJ). 2. The non-selective K+ channel blockers,
      4-aminopyridine (4-AP, 50 microM) and tetraethylammonium (TEA, 1 mM) and the more
      selective blocker of Ca(2+)-activated K+ channels, charybdotoxin (Leiurus
      quinquestriatus venom (LQV), 0.4 microgram ml-1), significantly enhanced the
      release of NO-R induced by low frequency stimulation (2-4 Hz). In the presence of
      4-AP and TEA, the release of NO-R was nearly abolished by tetrodotoxin (2
      microM), and by L-NG-nitroarginine (L-NOARG, 0.1 mM). Relaxations induced by
      direct injection of exogenous NO (5-50 pmol) or nitroglycerin (GTN, 10-30 pmol)
      onto the rabbit aortic detector ring were not affected. 3. The alpha 2
      adrenoceptor agonist, UK-14,304 (0.3 microM) inhibited the release of NO-R
      induced by low (2-4 Hz), but not that induced by high (16 Hz), frequency
      stimulation. This inhibitory effect was completely reversed by the alpha 2
      adrenoceptor antagonist, yohimbine (0.3 microM). Neither UK-14,304 nor yohimbine
      affected the relaxations induced by exogenous NO (5 pmol) or GTN (10 pmol) on the
      aortic detector ring.3+

PMID- 7518310
TI  - Expression of P2 protein by Lewis rat Schwann cells in vitro.
AB  - P2 protein is found in Schwann cells of the peripheral nervous system (PNS) in
      vivo and is a component of the myelin sheath. In previous studies by the authors,
      there have been indications that in vitro, Schwann cells can process and present
      endogenous P2 peptides to P2-specific T-cells capable of effecting experimental
      allergic neuritis (EAN) in the Lewis strain of rat. EAN is an animal model of
      Guillain-Barre syndrome, a human autoimmune disease of the PNS. However, previous
      studies have shown no evidence of expression of P2 protein by Schwann cells.
      Therefore, the aim of this study was to determine whether P2 is present in
      freshly dissociated Lewis rat Schwann cells and thus an endogenous source of
      peptides. In contrast to previous studies, we found P2 to be present in
      detectable levels within the cytoplasm of most Schwann cells up to 1 week in
      vitro, with the level of expression varying from cell to cell.

PMID- 7518309
TI  - Metabolism of methylarginines by human vasculature; implications for the
      regulation of nitric oxide synthesis.
AB  - 1. The metabolism of methylarginines by human cultured endothelial cells and
      human saphenous vein was studied in vitro. The human endothelial cell line (SGHEC
      7), primary cultures of human umbilical vein endothelial cells (HUVEC) and human
      saphenous vein were incubated with [14C]-monomethyl-L-arginine ([14C]-L-NMMA) and
      the cytosolic extract analysed by high performance liquid chromatography
      (h.p.l.c.) with on-line radioisotope detection. 2. SGHEC-7, HUVEC and human
      saphenous vein metabolized [14C]-L-NMMA to a compound which co-eluted with [14C]
      citrulline. A second metabolite which co-eluted with [14C]-arginine was evident
      on the radiochromatograms of HUVEC cytosol and saphenous vein extracts. 3. The
      intracellular levels of [14C]-L-NMMA and [14C]-citrulline in SGHEC-7 cells
      incubated with [14C]-L-NMMA (0.5 microCi ml-1: 8.9 microM) for 1 h were 113 +/-
      22 and 67.6 +/- 6.2 pmol mg-1 cell protein respectively (n = 7). Co-incubation
      with NGNGdimethyl-L-arginine (ADMA; 100 microM) but not NGNGdimethyl-L-arginine
      (SDMA; 100 microM) reduced the intracellular level of [14C]-citrulline to 26.3 +/
      3.7 pmol mg-1 cell protein (P < 0.01; n = 3) without reducing the intracellular
      level of [14C]-L-NMMA. 4. The intracellular levels of [14C]-citrulline in SGHEC-7
      cells incubated with [14C]-L-NMMA for 1 h were reduced following co-incubation
      with NGnitro-L-arginine methylester (L-NAME; 1 mM), NGnitro-L-arginine (L-NOARG;
      1 mM) and L-canavanine (1 mM) to 47.1 +/- 6.2, 24.7 +/- 3.6 and 12.5 +/- 2.8% of
      control levels (P < 0.001; n = 9). ADMA (1 mM; n = 3) reduced intracellular [14C]
      citrulline levels to4 +/- 4% of control (P<0.01) but SDMA (1 mM; n = 3) had no
      effect.5. The accumulation of endogenously synthesized ADMA in the culture
      supernatant of SGHEC-7 cells was increased by co-incubation with L-NMMA (1 mM)
      from 1.98 +/- 0.08 to 2.74 +/- 0.36 nmol mg- cell protein, an increase of 40%.6.
      These results demonstrate that human vasculature possesses an enzyme which has
      similar properties to dimethylarginase; human endothelial cells and human
      saphenous vein metabolize L-NMMA to citrulline via a process inhibited by ADMA
      but not SDMA. The increase in endothelium-derivedADMA following co-incubation
      with L-NMMA is consistent with competition between ADMA and L-NMMA for
      dimethylarginase. Inhibition of this enzyme might increase the intracellular
      concentration of ADMA, an endogenously produced compound that inhibits nitric
      oxide synthesis.

PMID- 7518313
TI  - [Diagnostic informative value of enzyme tests in the detection of pancreatic
      involvement in systemic scleroderma].
AB  - Thirty-three patients with systemic scleroderma were examined using a complex of
      enzymatic tests to detect pancreatic involvement. The diagnostic informative
      value of these tests was found to be not inferior to that of acknowledged
      instrumental methods of examination: pancreatic involvement was detected in 25 of
      the 33 patients with systemic scleroderma.

PMID- 7518312
TI  - Clinical application of nebulized opioids for treatment of dyspnoea in patients
      with malignant disease.
AB  - This article describes our experience in the clinical use of nebulized opioids
      for the management of dyspnoea in patients with terminal cancer by reviewing
      three specific patient case studies in which this treatment was found to be both
      safe and effective in controlling breathlessness. The patients were treated with
      morphine, hydromorphone or anileridine in various doses according to their prior
      use of opioids. Additional formal studies are being initiated at this Centre.

PMID- 7518311
TI  - Specific recognition of the human neuroendocrine receptor for vasoactive
      intestinal peptide by anti-peptide antibodies.
AB  - Rabbit polyclonal IgG antibodies were generated to three distinct synthetic
      peptide substituents of the human neuroendocrine-type 7 transmembrane-domain
      receptor for vasoactive intestinal peptide (VIP), including a portion of the
      amino-terminus, first extracellular loop, and carboxyl-terminus.
      Immunofluorescent staining of both human K293 cell transfectants, expressing
      recombinant VIP receptors, and HT-29 human intestinal epithelial cells, bearing
      native VIP receptors, was observed with each of the antibodies and was eliminated
      specifically after absorption of antibodies with the respective peptide
      immunogen. Each of the antibodies recognized the same approximately 70-kDa
      membrane proteins, extracted from both K293 cell transfectants and HT-29 cells,
      in sodium dodecyl sulfate-polyacrylamide gel electrophoresis blots. Neither IgG
      nor Fab preparations of the antibodies inhibited VIP binding to cellular
      receptors at a concentration of 1 microgram/ml, that yielded optimal
      immunofluorescence, or at 5-300 micrograms/ml. In contrast, 5-200 micrograms/ml
      of anti-peptide antibodies as IgG, but not Fab, significantly inhibited the
      increase in concentration of cyclic AMP in HT-29 cells elicited by 1 nM VIP,
      without affecting the greater increase evoked by 100 nM VIP or alone altering the
      level of cyclic AMP. Antibodies to several peptide substituents thus bind
      specifically to VIP receptors in immunoblots and permeabilized cells, and may
      affect the cellular functions of VIP receptors with sufficient selectivity to
      reduce transduction of signals, without altering the binding of VIP.

PMID- 7518315
TI  - [Use of granulocyte colony-stimulating factor for assessment of the bone marrow
      reserve].

PMID- 7518314
TI  - [Enzyme immunoassay of human chorionic beta-gonadotropin in biological fluids
      using photographic detection].
AB  - Potentialities of a new detection method making use of photographic information
      transformers were demonstrated as exemplified by enzyme immunoassay of human
      chorionic beta-gonadotropin. Commercial enzyme immunoassay kits for measurements
      of human chorionic beta-gonadotropin manufactured by Diaplus joint venture were
      used in the study. The results of traditional spectrophotometric detection and
      photographic detection were in good correlation, the correlation coefficient r
      being equal to 0.882. The sensitivity of the method permits reliable testing of
      clinically significant gonadotropin concentrations in biologic fluids.

PMID- 7518316
TI  - [New trends in the clinical laboratory].

PMID- 7518317
TI  - [A method for determining the strength of the disulphide bonds of glycoproteins
      from gastric mucus].
AB  - The author describes a simple and highly informative method for the assessment of
      disulfide bonds of gastric mucus glycoproteins, based on studies of the mucus
      rheology before and after incubation with 5% unithiol for an hour at 37 degrees
      C. Such an exposure was found to induce in normal subjects just a slight
      reduction of viscous elastic characteristics of the mucus (under 30% of the
      initial values), whereas in patients with duodenal ulcer this reduction was
      marked: in 83 +/- 7% of patients the rheologic characteristics dropped by more
      than 30%, in 1/3 of the patients the mucous gel was found completely dissolved.
      Such an effect was observed both in the patients with the initially reduced and
      with normal rheologic parameters of gastric mucus.

PMID- 7518318
TI  - Volume determinations of the whole prostate and of adenomas by transrectal
      ultrasound in patients with clinically benign prostatic hyperplasia: correlation
      of resected weight, blood loss and duration of operation.
AB  - OBJECTIVE: To study whether transrectal ultrasound (TRUS) volume determinations
      of the whole prostate and of the adenomas alone correlate to resected weight,
      operation time and blood loss in patients operated upon with transurethral
      resection of the prostate because of presumed benign prostatic hyperplasia (BPH).
      PATIENTS AND METHODS: The whole prostate and the transition zone, which
      corresponds to the adenomas, were measured separately in 159 patients with
      presumed BPH, pre-operatively and 4 months post-operatively. RESULTS: The
      transition zone volume correlated well with the resected weight (r = 0.91; P <
      0.0001), the blood loss (r = 0.67; P < 0.0001) and the operation time (r = 0.67;
      P < 0.0001). Four months post-operatively a reduction of the total prostate
      volume was recorded which corresponded well with the resected weight (r = 0.91; P
      < 0.0001). CONCLUSION: TRUS with high resolution 7 MHz probes successfully
      estimated the size of the whole prostate and that of the adenomas alone. The
      transition zone volume predicted the expected resection weight of adenomas and to
      some extent the duration of the operation and the blood loss. These calculations
      may be used for more accurate pre-operative planning. Together with its superior
      detection rate for prostate cancer, TRUS seems to be a powerful tool in the pre
      operative morphological assessment of patients with prostatism.

PMID- 7518319
TI  - Transurethral resection of the prostate for benign prostatic hypertrophy: factors
      associated with a successful outcome at 1 year.
AB  - OBJECTIVE: To investigate which patient and health service factors are predictive
      of outcome following transurethral resection for benign prostatic hypertrophy.
      PATIENTS AND METHODS: A total of 388 men were assessed before and 3, 6 and 12
      months following surgery. Twenty-one patient characteristics and 12 health
      service factors were considered. Successful outcome was assessed in terms of
      avoidance of adverse effects of the operation (survival, lack of early
      complications and later problems) and improvement in symptoms, health status
      (assessed in three ways) and quality of life. An overall assessment based on all
      eight outcome measures was also used. Relationships between possible predictors
      and outcome were explored whilst controlling for three potential confounders:
      age, diagnostic category and co-morbidity. A linear logistic model was employed.
      RESULTS: Patients who had severe pre-operative symptoms but who otherwise enjoyed
      good health gained the most benefit from surgery. Generally speaking, outcome was
      not associated with any of the 12 health service factors studied. CONCLUSION: The
      results support the policy of watchful waiting for mild or moderately symptomatic
      patients as even if surgery becomes necessary because of a deterioration in the
      condition, the benefit resulting will be greater. However, any benefits of
      waiting for surgery would have to be balanced against any increase in urinary
      tract pathology or co-morbidity that men may suffer whilst waiting, as these will
      increase the likelihood of an adverse outcome of surgery. The question of whether
      to wait or not will only finally be resolved by means of a randomized controlled
      trial comparing transurethral resection of the prostate with watchful waiting.

PMID- 7518320
TI  - Comparative study of selective alpha 1-adrenoceptor blockade versus surgery in
      the treatment of prostatic obstruction.

PMID- 7518321
TI  - Human in vivo evidence for trigeminovascular activation in cluster headache.
      Neuropeptide changes and effects of acute attacks therapies.
AB  - Cluster headache is a rare very severe disorder that is clinically well
      characterized with a relatively poorly understood pathophysiology. In this study
      patients with episodic cluster headache fulfilling the criteria of the
      International Headache Society were examined during an acute spontaneous attack
      of headache to determine the local cranial release of neuropeptides. Blood was
      sampled from the external jugular vein ipsilateral to the pain before and after
      treatment of the attack. Samples were assayed for calcitonin gene-related peptide
      (CGRP), vasoactive intestinal polypeptide (VIP), substance P and neuropeptide Y.
      Attacks were treated with either oxygen inhalation, sumatriptan or an opiate.
      Thirteen patients were studied of whom 10 were male and three female. All had
      well-established typical attacks of cluster headache when blood was sampled.
      During the attacks external jugular vein blood levels of CGRP and VIP were raised
      while there was no change in neuropeptide Y or substance P. Calcitonin gene
      related peptide levels rose to 110 +/- 7 pmol/l (normal: < 40) while VIP levels
      rose to 20 +/- 3 pmol/l (normal: < 7). Treatment with both oxygen and
      subcutaneous sumatriptan reduced the CGRP level to normal, while opiate
      administration did not alter the peptide levels. These data demonstrate for the
      first time in vivo human evidence for activation of the trigeminovascular system
      and the cranial parasympathetic nervous system in an acute attack of cluster
      headache. Furthermore, it is shown that both oxygen and sumatriptan abort the
      attacks and terminate activity in the trigeminovascular system.

PMID- 7518323
TI  - Responses of rat suprachiasmatic nucleus neurons to substance P and glutamate in
      vitro.
AB  - The suprachiasmatic nucleus (SCN), a circadian pacemaker in the mammalian brain,
      receives photic information directly from the retina via the retinohypothalamic
      tract (RHT). Although the neurotransmitters of the RHT have not yet been
      identified, it is known that glutamate (Glu) and substance P (SP) are present in
      RHT axons. We report the responses of spontaneously firing SCN neurons to Glu and
      SP examined in isolated brain slices. 43% of the neurons show an excitatory
      response (an increase in firing rate) and 11% an inhibitory response to bath
      applied SP at a concentration of 10(-7) M. Glu evokes excitatory responses from
      SCN neurons in a dose-dependent manner (10(-6)-10(-4) M). No day-night difference
      is observed in the response of SCN neurons either to 10(-7) M SP or to 10(-4) M
      Glu. Bath-applied SP has additive effects on Glu-evoked responses and pressure
      ejected SP at a concentration of 0.8 mM strongly potentiates Glu responses. These
      results are consistent with the view that Glu and/or SP function as
      neurotransmitters, or modulators, in the RHT and suggest that cellular processes
      downstream of the activation of SP or Glu receptors mediate time-dependent phase
      responses of SCN neurons.

PMID- 7518324
TI  - Sensory C-fibers in rat ventral roots are capsaicin-insensitive and they do not
      mediate extravasation from pial vessels.
AB  - Mammalian ventral roots and pia mater contain sensory C-fibers, some of which
      exhibit a substance P- and/or calcitonin gene-related peptide (CGRP)-like
      immunoreactivity. At some locations, sensory axons containing these neuropeptides
      evoke peripheral plasma protein extravasation after antidromic electrical
      stimulation. Such axons usually disappear following treatment of neonatal rats
      with capsaicin. The purpose of the present study is to find out if afferent C
      fibers in the rat ventral roots L4 and L5 are capsaicin-sensitive, and if
      antidromic stimulation of these fibers elicits extravasation in the root and/or
      the ventral pia mater. The results show (1) that the number of C-fibers in these
      ventral roots is unaffected by neonatal capsaicin treatment, as seen in the
      electron microscope; (2) that the occurrence and general configuration of axons
      with substance P- and CGRP-like immunoreactivity do not appear abnormal in
      neonatally capsaicin-treated rats, as revealed by fluorescence microscopy on
      longitudinal frozen sections; (3) that Evans blue albumin is not extravasated in
      the ventral root or pia mater after electrical ventral root stimulation or
      following systemic injection of capsaicin. We conclude, that ventral root
      afferents are functionally different from otherwise similar afferents at other
      locations.

PMID- 7518325
TI  - Fucose and fucose-containing sugar epitopes enhance hippocampal long-term
      potentiation in the freely moving rat.
AB  - Male Wistar rats were intrahippocampally injected with L-fucose and the sugar
      epitope 2'-fucosyl-lactose prior to induction of long-term potentiation (LTP).
      Both substances had only a minimal and short-lasting depressive effect on the
      monosynaptically evoked field potential recorded in the dorsal blade of the
      dentate gyrus of freely moving rats upon stimulation of the perforant pathway.
      However, LTP induced by fractionated tetanization of the perforant pathway, which
      declined within 24 h in control animals injected with Lactose, remained at the
      initial level even 48 h after tetanization (difference to the control group
      significant with P < 0.01). The results support earlier findings which have
      indicated a participation of fucosylated macromolecules in the maintenance of
      LTP. Different molecular mechanisms concerning the effect of both substances and
      the significance of the data in elucidation of the relationship between LTP and
      memory formation are discussed.

PMID- 7518322
TI  - Comparative effects of NG-monomethyl-L-arginine and MK-801 on the abstinence
      syndrome in morphine-dependent mice.
AB  - The effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide
      (NO) synthase and MK-801, an NMDA receptor antagonist on abrupt and naltrexone
      precipitated abstinence symptoms were determined in male Swiss-Webster mice
      rendered dependent on morphine by subcutaneous implantation of a pellet
      containing 75 mg of morphine base for 3 days. Mice which served as controls were
      implanted with placebo pellets. Six hours after pellet removal, mice were
      injected intraperitoneally with either the vehicle or MK-801 (0.03, 0.1 and 0.3
      mg/kg). Thirty minutes later the animals were injected with naltrexone
      subcutaneously (50 micrograms/kg) and the intensity of abstinence symptoms were
      determined. Of the three doses of MK-801 used, only 0.1 mg/kg dose inhibited the
      jumping behavior precipitated by naltrexone in morphine-dependent mice. Whereas
      the lower dose (0.03 mg/kg) of MK-801 increased, the higher doses of MK-801 (0.1
      and 0.3 mg/kg) displayed a decrease in the formation of fecal boli.
      Administration of MK-801 did not affect the body weight loss observed during
      abrupt withdrawal (induced by removal of the pellets) in morphine-dependent mice.
      MK-801 at 0.1 mg/kg dose further decreased the body temperature during abrupt
      withdrawal in morphine-dependent mice. Other two doses of MK-801 (0.03 and 0.3
      mg/kg) did not modify the hypothermia observed during abrupt morphine withdrawal.
      On the other hand, L-NMMA (0.02 to 4.0 mg/kg) injected intraperitoneally 15 min
      prior to the naltrexone administration blocked the stereotyped jumping response
      in a dose-dependent manner. Higher doses of L-NMMA 2.0 and 4.0 mg/kg also
      decreased the number of fecal boli formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518328
TI  - Arachidonic acid depresses non-NMDA receptor currents.
AB  - Arachidonic acid has been proposed as an intercellular messenger in the nervous
      system. It is released when glutamate acts on postsynaptic receptors, potentiates
      NMDA receptor currents and depresses glutamate uptake. Here we report the effects
      of arachidonic acid on non-NMDA receptor currents, studied by whole-cell clamping
      isolated neurons and neurons in tissue slices. In cultured cerebellar granule
      cells and in freshly isolated hippocampal pyramidal cells arachidonic acid
      decreased the current produced by iontophoresed AMPA. This depression was not due
      to increased desensitization of the AMPA receptor. In cerebellar slices,
      arachidonic acid depressed the non-NMDA component of the synaptic current at the
      mossy fibre to granule cell and the parallel fibre to Purkinje cell synapses.
      However, this depression was not always seen, possibly because the lipophilic
      arachidonic acid is absorbed by superficial cells in the slice and does not reach
      the synapse being studied. Depression of non-NMDA receptor currents by
      arachidonic acid may reflect the presence of an arachidonic acid binding site on
      the non-NMDA receptor, but non-NMDA receptor subunits show much less sequence
      homology with fatty acid binding proteins than does the NMDA receptor.

PMID- 7518326
TI  - Effect of local infusion of glutamate analogues into the nucleus accumbens of
      rats: an electrochemical and behavioural study.
AB  - In vivo voltammetry at electrochemically pretreated carbon fibre electrodes was
      used to investigate the effect of local infusion of glutamate analogues on
      dopamine (DA) release in rat nucleus accumbens. Infusion of a low dose of NMDA or
      AMPA (1 mM/0.2 microliter), but not L-glutamate or kainate, was followed a few
      minutes later by a large but short-lived increase in the extracellular
      concentration of DA. The involvement of spreading depression was indicated since
      this response could be repeated only after a short refractory period, and the
      response magnitude did not seem to be dependent on the dose infused. Furthermore,
      the increase in DA release was accompanied by a marked negative shift in brain
      field potential and a similar increase in release could be induced by local
      infusion of K+. The infusion of NMDA, AMPA or kainate was followed by behavioural
      activation of the animals but not convulsions. The behavioural response induced
      by NMDA was dose-dependently reduced by haloperidol, which suggests the
      involvement of a DA-dependent mechanism in this effect. Co-infusion of the DA
      transport inhibitors, nomifensine or GBR 12909, failed to alter the DA response
      to NMDA, while this response was completely blocked by co-infusion of
      tetrodotoxin or pretreatment with reserpine. It is evident from this study that
      local infusion of NMDA or AMPA may induce spreading depression in rat nucleus
      accumbens and that this condition is associated with a vast release of DA and
      behavioural activation.

PMID- 7518327
TI  - Effects of repeated administration of a high dose of methamphetamine on dopamine
      and glutamate release in rat striatum and nucleus accumbens.
AB  - We examined effects of a high dose of methamphetamine (MA) (4.02 mg free base/kg,
      s.c., at 2-h intervals, 4 injections) on extracellular concentrations of
      monoamines such as dopamine (DA), dihydroxyphenylacetic acid (DOPAC),
      homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) and those of
      glutamate and other several amino acids in rat striatum (ST) and nucleus
      accumbens (NA) using in vivo microdialysis. Five days after the microdialysis,
      tissue concentrations of monoamines were measured. The toxic dose of MA markedly
      increased extracellular concentrations of DA, and decreased those of DOPAC, HVA
      and 5-HIAA in both ST and NA. Magnitude of the increase in DA release was not
      different between ST and NA. Extracellular concentrations of glutamate showed a
      gradual increase in ST, but not in NA, while other amino acids showed no changes
      in both ST and NA. Tissue concentrations of serotonin (5-HT) and 5-HIAA were
      decreased to 43-58% of control values in both ST and NA, whereas those of DA,
      DOPAC and HVA showed 43-54% decrease in ST but no changes in NA. These data
      suggest that the marked increase of DA release is not directly related to the MA
      induced dopaminergic neurotoxicity. The increase in glutamate release found only
      in ST may be related to the dopaminergic damage in ST. It may be that enhanced
      release in DA and glutamate act synergistically to cause the dopaminergic
      neurotoxicity in ST. However, enhancement in glutamate release did not appear to
      be essential for the MA-induced serotonergic neurotoxicity.

PMID- 7518329
TI  - Substance P and other putative transmitters modulate the activity of reticular
      pontine neurons: an electrophysiological and immunohistochemical study.
AB  - In this study we investigated the effects of possible modulatory transmitters on
      acoustically responsive neurons of the caudal pontine reticular nucleus (PnC).
      From previous work in our laboratory it has been suggested that the acoustically
      responsive giant neurons of this nucleus are the sensorimotor interface mediating
      the acoustic startle response. Furthermore they are the site of some of the
      modulatory influence impinging on this response. Besides a possibly glutamatergic
      excitation from the amygdala a cholinergic input from the midbrain has been
      described which may use substance P as cotransmitter. Therefore we used
      electrophysiological and histochemical methods to study this possible modulatory
      influence in the caudal pontine reticular nucleus. In the first part of this
      study we recorded extracellularly from single units in the PnC in vivo and
      studied the effects of iontophoretically applied transmitters. Substance P
      elicited a long lasting excitation. This excitatory effect of SP was potentiated
      by acetyl-beta-methylcholine (AMCh, an acetylcholine agonist), whereas single
      application of AMCh showed no uniform response. Glutamate elicited a potent brief
      excitation, while application of GABA showed a potent brief inhibition of PnC
      neurons. In the second part of this study we employed immunoperoxidase staining
      for substance P, which revealed a fairly dense network of substance P
      immunoreactive (SP-ir) fibers in the lateral and ventral aspects of the PnC.
      Combining retrograde tracing and immunocytochemistry for substance P, we
      demonstrated that the SP-ir axons in the PnC originate mainly in the laterodorsal
      tegmental nucleus. We therefore conclude that activation of the laterodorsal
      tegmental nucleus may facilitate the acoustic startle response by a long lasting
      excitation of neurons in the caudal pontine reticular nucleus.

PMID- 7518330
TI  - Potassium and calcium channel dependence of bursting in cultured neuronal
      networks.
AB  - Increases in extracellular potassium concentrations reliably increase burst rates
      in cultured fetal murine spinal cord networks. This effect could be mimicked by
      either blocking voltage-gated potassium conductances or facilitating excitatory
      synaptic interactions, but not by blocking specific calcium-dependent potassium
      conductances or tonic depolarization. Spontaneous bursting in cultured networks
      is apparently dependent on potassium currents and intracellular calcium levels,
      but not on the pharmacologically characterized calcium-dependent potassium
      conductances.

PMID- 7518331
TI  - Amyloid beta-peptide (A beta P) potentiates a nimodipine-sensitive L-type barium
      conductance in N1E-115 neuroblastoma cells.
AB  - The neurodegenerative pathology observed in Alzheimer's Disease (AD) has been
      partially attributed to the neurotoxic effects of the amyloid beta-peptide (A
      beta P), although the mechanisms underlying this neurotoxicity are unknown. Since
      A beta P is capable of forming cation channels in lipid bilayers, it is possible
      that the neurotoxic effects on neurons may be mediated by a cation flux. We have
      used patch-clamp recording techniques to study the effects of A beta P on cation
      currents in differentiated mouse N1E-115 neuroblastoma cells. In whole-cell
      recordings, incubation of cells with A beta P for 24 h significantly increased
      the median peak inward current from -201.8 pA to -352.0 pA, and shifted the
      voltage at peak current (Vpeak) and that of current activation (Vact) towards
      more positive potentials. For untreated cells, median Vpeak was 1.7 mV and Vact
      was -28.9 mV, vs. 10.5 mV and -24.7 mV in A beta P-treated cells. Incubation with
      the reverse sequence A beta P(40-1) or A beta P(25-35) did not produce
      significant changes in the amplitude or kinetic behavior of the inward current.
      At the single channel level, A beta P added to the pipette increased the open
      probability of cation-conducting ion channels. As determined by cell viability
      counts, both A beta P(1-40) and the A beta P(25-35) fragment had neurotoxic
      effects; within 24 h, addition of A beta P reduced the number of viable cells by
      more than 50%. It is suggested that the neurotoxic effects of A beta P may be
      mediated by its ability to form cation channels de novo and/or alter the activity
      of cation channels already present in the cell membrane.

PMID- 7518333
TI  - Effects of lindane (gamma-BHC) and related convulsants on GABAA receptor-operated
      chloride channels in frog dorsal root ganglion neurons.
AB  - Effects of lindane (gamma-benzenehexachloride; gamma-BHC) on GABA-evoked Cl-
      current (IGABA) in freshly dissociated frog sensory (dorsal root ganglion)
      neurons were studied and compared with those of tert-butylbicycloortho benzoate
      (TBOB) and picrotoxin by the use of the suction-pipette method [13]. Drugs were
      applied with a rapid drug-application method, "Concentration-clamp" technique. At
      concentration of GABA of > 3 x 10(-6) M, at least two components of the IGABA
      were recognized distinct degree of desensitization. Those were defined as the
      peak and plateau components in the text. At low concentration (3 x 10(-7) M) of
      gamma-BHC, only the plateau component of IGABA at 10(-5) M were depressed without
      changing the peak amplitude. While gamma-BHC at high concentration (3 x 10(-5) M)
      depressed both the peak and plateau current components. The gamma-BHC-induced
      depression of IGABA seemed to be IGABA-component-dependent. A detailed analysis
      of the gamma-BHC action in the concentration-response relationship for GABA
      revealed that the IGABA with strong desensitization was preferentially blocked by
      gamma-BHC (3 x 10(-5) M). The rate of recovery of the IGABA from gamma-BHC
      induced block depended on the concentration of GABA. The lower the concentration
      of GABA, the slower the recovery. The GABAA receptor Cl- channels were proposed
      to be classified into two types of the gamma-BHC-sensitive and -resistant
      ones.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518332
TI  - Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and 
      6.
AB  - Cytokine-specific alterations of monoamine activity were evident in the
      hypothalamus, hippocampus and prefrontal cortex 2 h following peripheral
      administration of recombinant interleukin (IL)-1 beta, IL-2 and IL-6 (200 ng,
      i.p.) in male, BALB/c mice. IL-1 induced the broadest range of neurochemical
      changes, affecting central norepinephrine (NE), serotonin (5-HT) and dopamine
      (DA) activity. In particular, IL-1 enhanced NE turnover in the hypothalamus and
      hippocampus, 5-HT turnover in the hippocampus and prefrontal cortex (owing to
      increased utilization and reduced content of the transmitters in these brain
      regions), and enhanced DA utilization in the prefrontal cortex. IL-6 increased 5
      HT and DA activity in the hippocampus and prefrontal cortex in a manner similar
      to IL-1, but failed to affect central NE activity. Moreover, IL-2 increased
      hypothalamic NE turnover (reflecting a profound increase in NE utilization) and
      enhanced DA turnover in the prefrontal cortex, but did not influence central 5-HT
      activity. Hence, these cytokines differentially altered neurochemical activity in
      brain regions that mediate neuroimmune interactions and that are influenced by
      physical and psychological stressors. In addition to the neurochemical changes,
      plasma corticosterone concentrations were profoundly enhanced in IL-1-treated
      animals, but not significantly altered by IL-2 or IL-6 treatment. The IL-1
      induced corticosterone elevations did not significantly correlate with
      alterations of hypothalamic NE activity.

PMID- 7518334
TI  - Effect of neurotransmitters on axoplasmic transport: how adrenaline affects
      superior cervical ganglion cells.
AB  - The effect of adrenaline on the axoplasmic transport of cultured superior
      cervical ganglion cells was analyzed with a computer-assisted video-enhanced
      differential interference contrast microscope system. Adrenaline increased the
      axoplasmic transport reversibly in both anterograde and retrograde directions. A
      beta 2-antagonist, butoxamine, antagonized the increasing effects of adrenaline,
      but alpha-antagonists and beta 1-antagonists did not. A beta 2-agonist,
      albuterol, mimicked the adrenaline effect, but beta 1-, alpha 1-, alpha 2
      agonists did not. The adrenaline receptor may be a beta 2-receptor. Dibutyryl
      cyclic AMP and forskolin increased the axoplasmic transport. Therefore,
      adrenaline increases the axoplasmic transport by raising the cyclic AMP level. In
      light of our former report that acetylcholine suppresses the axoplasmic
      transport, neurotransmitters control axoplasmic transport and this
      neurotransmitter control reflects the activity of the nerve cell.

PMID- 7518339
TI  - Medical complications of polydipsia in nonpsychotic depression.

PMID- 7518337
TI  - The pontocerebellar projection: longitudinal zonal distribution of fibers from
      discrete regions of the pontine nuclei to vermal and parafloccular cortices in
      the rat.
AB  - A longitudinal parasagittal organization (alternating labeled and unlabeled
      stripes) of mossy fiber terminals in the paraflocculus and in the vermal lobule
      VII of the cerebellum was found after small injections (less than 50 nl) of wheat
      germ agglutinin-horseradish peroxidase (WGA-HRP) into discrete regions of the
      basilar pontine nuclei (BPN) of rats. Up to three stripes were found within the
      paraflocculus of both sides, following injections (of about 500 microns in
      diameter) in either the medial or lateral region of the caudal half of the BPN.
      Up to five stripes were found in the vermal lobule VII after similar size
      injections into the rostro-ventral region of the BPN. These results emphasize the
      possibility that the parasagittal zonal arrangement could be a common pattern of
      organization shared by climbing and mossy fiber afferents.

PMID- 7518336
TI  - NADPH diaphorase (nitric oxide synthase) in a part of the chick brain involved in
      imprinting.
AB  - The intermediate and medial part of the hyperstriatum ventrale (IMHV) is a memory
      system in the chick forebrain in which certain learning-related changes occur
      after imprinting. We have enquired whether NADPH-diaphorase, a presumed marker
      for nitric oxide synthase, is present in sections through the IMHV of chicks,
      either trained with an imprinting stimulus or dark-reared. Very few NADPH-d
      positive cells were found in the IMHV (0.37 +/- 0.07 S.E.M. cells per 0.3 mm x
      0.9 mm sampling frame), in contrast to the palaeostriatum augmentatum (PA) (19.47
      +/- 0.77). Some stained cells in the PA were closely associated with blood
      vessels. The results do not support the hypothesis that learning-related changes
      in the IMHV depend on nitric oxide acting as a retrograde neuronal messenger.

PMID- 7518335
TI  - Occurrence of galanin-like immunoreactivity in vestibular and cochlear efferent
      neurons after labyrinthectomy in the rat.
AB  - The origins of the vestibular and cochlear efferent systems lie in the lower
      brainstem and innervate the labyrinth. In the present study we investigated the
      changes in galanin-like immunoreactivity (GAL-IR) in the vestibular and cochlear
      efferent neurons in control and labyrinthectomized rats. In control animals, no
      GAL-IR was noticed in these neurons. However, in response to unilateral
      labyrinthectomy, similar GAL-IR was bilaterally expressed in the two systems. GAL
      immunostained cells appeared on postoperative day 3 and reached a peak of
      intensity and number at postoperative week 2. Retrograde tracing by fluorogold
      combined with GAL immunohistochemistry demonstrated that, except for the cells of
      the contralateral lateral superior olivary nucleus (LSO), GAL-IR neurons project
      into the lesioned labyrinth.

PMID- 7518338
TI  - Dystonic reaction and relapse with clozapine discontinuation and risperidone
      intiation.

PMID- 7518340
TI  - Plasma insulin-like growth factor I and its binding proteins 1 and 3 in
      postmenopausal patients with breast cancer receiving long term tamoxifen.
AB  - BACKGROUND: Insulin-like growth factor I (IGF-I) is a potent mitogen for breast
      cancer cells. The majority of IGF-I in plasma is bound to IGF binding proteins
      (IGFBPs), which modulate the biologic effects of IGF-I. METHODS: Plasma
      concentrations of IGF-I, IGFBP-I, and IGFBP-3 were compared between 40
      postmenopausal breast cancer patients receiving long term tamoxifen therapy and
      39 breast cancer patients receiving no hormonal treatment. In an additional group
      of seven patients, serum levels of IGF-I and IGFBP-1 were determined before and
      during treatment at 6 and 12 months. RESULTS: The tamoxifen and the control
      groups did not differ with respect to age, parity, age at menopause, or body mass
      index. There were no significant differences in the mean concentrations (+/-
      standard error of the mean) of IGF-I (10.0 +/- 0.4 nmol/l and 11.2 +/- 0.5
      nmol/l, respectively) and IGFBP-3 (3.2 +/- 0.1 mg/l and 3.1 +/- 0.1 mg/l,
      respectively), whereas the mean value of IGFBP-1 was significantly higher in the
      tamoxifen group (6.0 +/- 0.6 micrograms/l versus 2.8 +/- 0.3 micrograms/L, P =
      0.0001). No significant differences were found in the insulin levels. During the
      treatment, concentrations of IGF-I decreased at 6 months and began increasing at
      12 months. IGFBP-1 levels increased at 6 months and remained elevated at 12
      months. CONCLUSIONS: The tamoxifen-induced increase in IGFBP-1 plasma levels may
      be an important mechanism modulating IGF-I action at the tissue level.

PMID- 7518341
TI  - Prostate specific antigen doubling time and disease relapse after radiotherapy
      for prostate cancer.
AB  - BACKGROUND: Serum prostate specific antigen (PSA) correlates with prostate tumor
      volume. Therefore, PSA-doubling time (PSA-DT) in patients with a rising PSA
      profile after radiotherapy should be predictive of the time to clinical disease
      relapse. The purpose of this study was to characterize the relationship between
      PSA-DT and the time to disease relapse after the onset of a rising PSA (PSA-TTR)
      in 427 men treated in the PSA-era with high dose radiotherapy for Stages T1-4
      adenocarcinoma of the prostate. METHOD: There were 119 patients with a rising PSA
      profile after radiotherapy, and of these, there was sufficient information to
      calculate PSA-DT using nonlinear least squares regression in 100. There were 44
      patients in this cohort who had documented disease relapse. The median patient
      follow-up was 38 months. RESULTS: The average PSA-DT was 13.5 plus or minus 11.6
      mo (+/- standard deviation). PSA-DT values correlated with tumor grade,
      pretreatment PSA, and stage. PSA-DT was also strongly related to the outcome
      measures of local relapse, distant metastases, and any disease relapse. The
      shorter the PSA-DT, the greater the risk of disease relapse. The average PSA-TTR
      was 10.1 plus or minus 8.2. The only prognostic factor that correlated with PSA
      TTR was tumor grade. A linear regression analysis of normalized PSA-DT and PSA
      TTR revealed a significant correlation in which a PSA-DT of 11 months predicted
      for disease relapse 24 months later. Because several factors including physician
      and patient preferences could alter this relationship, a comparison was made
      between the actuarial PSA rise time for patients treated in the PSA-era and
      actuarial clinical disease relapse using a cohort of similarly treated men from
      the pre-PSA-era (n = 798). The results showed the lead time to be over 40 months
      in the majority of patients and that this lead time was much shorter in those
      with high grade tumors. CONCLUSIONS: PSA-DT is a strong prognostic factor for
      patients with biochemical evidence of failure after radiotherapy. A short PSA-DT
      predicts for more rapid progression to symptoms. The timing of the progression
      from a rising PSA to clinical disease relapse is probably longer than expected
      and is estimated to be 40 months on average.

PMID- 7518342
TI  - Steady state transcript levels of the type II hexokinase and type 1 glucose
      transporter in human tumor cell lines.
AB  - The steady state transcript levels of two hexokinase isozymes and type 1 glucose
      transporter in human tumor cell lines were analyzed. In HepG2 cells, both type II
      hexokinase and type 1 glucose transporter were highly expressed. However, in cell
      lines A431 and HeLa, in which the expression level of type 1 glucose transporter
      was lower than that in HepG2 cells, the amount of type II hexokinase transcript
      was almost negligible.

PMID- 7518344
TI  - Paracrine growth stimulation by hepatocyte-derived insulin-like growth factor-1:
      a regulatory mechanism for carcinoma cells metastatic to the liver.
AB  - Tumor H-59 is a subline of the Lewis lung carcinoma which is highly and
      preferentially metastatic to the liver. We used this carcinoma model to
      investigate the role of paracrine growth regulation by liver-derived factors in
      this organ-selective pattern of metastasis. We observed that serum-free medium
      conditioned by primary cultures of mouse hepatocytes was highly and specifically
      mitogenic for H-59 cells but had little effect on the proliferation of a second
      subline, i.e., carcinoma M-27, which is metastatic only to the lung. This
      mitogenic activity was hepatocyte-specific and could be blocked or depleted by a
      monoclonal antibody to insulin-like growth factor 1 (IGF-1). IGF-1 could in turn
      be detected in hepatocyte conditioned medium by the Western blot assay, and when
      added to serum-deprived cells, IGF-1 could stimulate the proliferation of H-59
      but not M-27 cells. Furthermore, when expression of the IGF-1 receptor was
      analyzed by the Northern blot assay, we found that H-59 cells expressed
      significantly higher levels of mRNA transcripts encoding IGF-1 receptor. A ligand
      binding assay revealed that the number of IGF-1 binding sites on H-59 cells was
      3.4-fold higher than that on M-27 cells. The results identify IGF-1 as the growth
      factor mediating the proliferative effect of hepatocyte conditioned medium and
      suggest that paracrine growth stimulation by hepatocyte-derived IGF-1 is a
      potential mechanism of selection in the process of liver colonization by these
      carcinoma cells.

PMID- 7518343
TI  - Characterization of a hydroxyurea-resistant human KB cell line with
      supersensitivity to 6-thioguanine.
AB  - Hydroxyurea (HU) is currently used in the clinic for the treatment of chronic
      myelogenous leukemia, head and neck carcinoma, and sarcoma. One of its drawbacks,
      however, is the development of HU resistance. To study this problem, we developed
      a HU-resistant human KB cell line which exhibits a 15-fold resistance to HU. The
      characterization of this HU-resistant phenotype revealed a gene amplification of
      the M2 subunit of ribonucleotide reductase (RR), increased levels of M2 mRNA and
      protein, and a 3-fold increase of RR activity. This HU-resistant cell line also
      expressed a "collateral sensitivity" to 6-thioguanine (6-TG), with a 10-fold
      decrease in the dose inhibiting cell growth by 50% as compared to the KB parental
      line. The mechanism responsible for this supersensitivity to 6-TG is believed to
      be related to an increasingly efficient conversion of 6-TG to its triphosphate
      form, which is subsequently incorporated into DNA. After passage of the resistant
      cells in the absence of HU, the cell line reverts. The revertant cells lose their
      resistance to HU and concomitantly their sensitivity to 6-TG. This phenomenon is
      due to the return of RR to levels comparable to that of the KB parental cell
      line. These observations and their relevance to cancer chemotherapy will be
      discussed in this paper. Our results suggest that a clinical protocol could be
      designed which would allow for a lower dose of 6-TG to be used by taking
      advantage of the increased RR activity in HU-refractory cancer patients. Two
      drugs which display collateral sensitivity are known as a "Ying-Yang" pair.
      Alternate treatment with two different Ying-Yang pairs is the rationale for the
      "Ying-Yang Ping-Pong" theory in cancer treatment. This rationale allows for
      effective cancer chemotherapy with reduced toxicity.

PMID- 7518346
TI  - Decreased E-cadherin expression is associated with poor prognosis in patients
      with prostate cancer.
AB  - Decreased levels of the cell-cell adhesion molecule E-cadherin are associated
      with loss of differentiation in a number of human carcinomas. However, the value
      of E-cadherin as a prognostic marker in these cancers is largely undetermined. A
      previous study of E-cadherin levels in prostate cancer revealed that almost 50%
      of tumors examined had reduced or absent levels of this protein (Umbas et al.,
      Cancer Res., 52: 5104-5109, 1992). To determine the potential prognostic
      significance of this finding, prostate cancer specimens from 89 patients were
      evaluated immunohistochemically for E-cadherin expression, and the results were
      related to histopathological grade, tumor stage, presence of metastases, and
      survival. As previously observed, a significant inverse correlation was found
      between E-cadherin expression and tumor grade. Importantly, we also found
      significant correlations between E-cadherin expression and tumor stage and
      overall survival. Sixty-three percent of the tumors that extended beyond the
      prostate capsule (T3-4) versus 33% of the tumors confined to the prostate (T1-2)
      had aberrant expression (chi 2 = 8.1, P < 0.005). Seventy-six percent of the
      primary tumors from patients that presented with metastases showed aberrant
      staining compared to 32% from patients without metastases (chi 2 = 14.9; P <
      0.001). The life table analysis showed a significantly higher survival rate for
      patients with normal staining compared to patients with aberrant expression (chi
      2 = 20.4, P < 0.001 by log rank test). Moreover, abnormal expression of E
      cadherin correlated significantly with progression after radical prostatectomy (P
      < 0.005). These results suggest that E-cadherin expression can serve as a
      prognostic indicator for the biological potential of prostate cancer.

PMID- 7518345
TI  - Expression of CD44 in normal human versus tumor endometrial tissues: possible
      implication of reduced expression of CD44 in lymph-vascular space involvement of
      cancer cells.
AB  - Alternatively spliced variants of the CD44 molecule have been found to be
      associated with invasive and metastatic potential of cancer cells and poor
      prognosis in several types of carcinoma. We have examined expression of CD44 in
      normal and cancerous tissues of the endometrium as well as in cell lines
      established from patients with endometrial cancers by the combination of reverse
      transcription-polymerase chain reaction and Southern blot hybridization and by
      cell surface staining with antibodies to CD44. Of eight cancer cell lines tested,
      two lines, HOOUA and HEC50B, both of which are possibly potential candidates for
      metastasis, expressed a very small amount of mRNA for CD44. Variant forms of CD44
      were expressed in 9 of 11 (81.8%) normal endometria, whereas 8 of 47 (17.0%)
      endometrial carcinomas showed expression of the variants. Hyperplasia samples
      displayed the variant expression in 42.9% of specimens (the value was between
      those of the normal and cancerous cells) and none of 3 in Mullerian mixed tumors.
      There was a significant difference in frequencies of CD44 variant expression
      between normal and cancerous tissues. Furthermore, lymph-vascular space
      involvement of cancer cells was observed to be statistically significant in the
      CD44-negative group as opposed to the positive group. Reverse transcription
      polymerase chain reaction and Southern blot hybridization clearly demonstrated
      that normal endometrial tissues express the standard CD44 form as well as the
      variant form. Immunohistochemical examination of normal endometrium revealed that
      intense staining was seen on the gland cells at the basement membrane side, and
      less intense staining was seen between the gland cells. These results suggest
      that CD44 could play important roles in the function of normal endometrium and
      that reduced CD44 expression might be related to the metastasis of endometrial
      cancer cells through lymph-vascular space.

PMID- 7518348
TI  - Aneuploidy and aneusomy of chromosome 7 detected by fluorescence in situ
      hybridization are markers of poor prognosis in prostate cancer.
AB  - Fluorescence in situ hybridization is a new methodology which can be used to
      detect cytogenetic anomalies within interphase tumor cells. We used this
      technique to identify nonrandom numeric chromosomal alterations in tumor
      specimens from the poorest prognosis patients with pathological stages T2N0M0 and
      T3N0M0 prostate carcinomas. Among 1368 patients treated by radical prostatectomy,
      25 study patients were ascertained who died most quickly from progressive
      prostate carcinoma within 3 years of diagnosis and surgery. Tumors from 25
      control patients who survival for more than 5 years and who were matched for age,
      tumor histological grade, and pathological stage also were evaluated. The tumors
      from all 25 (100%) poor prognosis patients and from 11 of 25 (44%) control
      patients were found to be aneuploid by fluorescence in situ hybridization (P <
      0.0001). Alterations of chromosome 7 were observed in 24 of the tumors (96%) from
      the poor prognosis patients versus 3 tumors (12%) from the control group (P <
      0.0001). Moreover, a characteristic aneuploidy pattern with multiple abnormal
      chromosomes and a hypertetrasomic population was generally found in tumors from
      the poor prognosis patients. This preliminary study suggests that fluorescence in
      situ hybridization studies of prostate cancer specimens may help to identify
      those patients at highest risk for early cancer death.

PMID- 7518347
TI  - CD44 mediates human glioma cell adhesion and invasion in vitro.
AB  - Human gliomas are characterized by their invasion of normal brain structures
      irrespective of their grade of malignancy. Factors involved in the control of
      this invasive behavior are poorly documented. Human gliomas have also been found
      to express CD44 adhesion molecules. Expression of splice variants of CD44 has
      been correlated to metastasis in nonglial solid tumors. In this study, 8-microns
      porosity polycarbonate filters incorporated in modified Boyden chambers and
      coated with the extracellular matrix composite Matrigel were used to investigate
      the role of CD44 in invasion of eight human glioma cell lines in vitro. Invasion
      of Matrigel was found to be inhibited to different extents by a CD44 monoclonal
      antibody. Moreover, this invasion was highly inhibited in two cell lines and
      completely arrested in five other glioma cell lines by a CD44-specific antisense
      oligonucleotide which inhibited CD44 expression. In addition, adhesion of glioma
      cells to fibronectin, laminin, vitronectin, and collagen I was inhibited by the
      CD44 monoclonal antibody. These results strongly suggest that CD44 is involved in
      human glioma cell invasion in vitro, probably through its role in cell
      interactions with extracellular matrix proteins. Interference with glioma
      invasion, by targeting CD44 expression, may be envisaged in animal models.

PMID- 7518350
TI  - Overexpression of the RI alpha subunit of protein kinase A confers
      hypersensitivity to topoisomerase II inhibitors and 8-chloro-cyclic adenosine
      3'5'-monophosphate in Chinese hamster ovary cells.
AB  - We have shown that a mutant derivative of Chinese hamster ovary CHO-K1 cells, ADR
      5, which shows hypersensitivity to topoisomerase II (topo II)-inhibitory drugs,
      is cross-sensitive to the site-selective cyclic AMP analogue 8-chloro-cyclic AMP.
      We tested the hypothesis that overexpression of the type I alpha regulatory
      subunit of protein kinase A may represent a common element conferring
      hypersensitivity to both topo II inhibitors and 8-chloro-cyclic AMP in ADR-5
      cells. We have demonstrated that ADR-5 cells overexpress RI alpha protein,
      compared to parental CHO-K1 cells. Moreover, retroviral vector-mediated transfer
      of the RI alpha gene into CHO-K1 cells was able to confer a drug-hypersensitive
      phenotype similar to that exhibited by ADR-5 cells. Analysis of topo II protein
      levels and activity revealed no differences between parental and infected cells,
      suggesting that protein kinase A may be involved in the downstream processing of
      topo II-mediated events.

PMID- 7518349
TI  - Detection of discrete androgen receptor epitopes in prostate cancer by
      immunostaining: measurement by color video image analysis.
AB  - To determine whether multiple features of immunohistochemical staining of the
      androgen receptor (AR) in prostate cancer could reliably predict androgen
      dependence, tumor biopsy specimens from 30 patients (stages A-D2) were stained
      using anti-peptide antibodies to the amino- and carboxyl-terminal of the AR.
      Measurements were made of the mean area and total amount (i.e., integrated
      optical density) of AR staining in at least 20 fields per section using a color
      video image analysis system, and the mean intensity of AR staining per cell and
      the percentage of AR positive tumor cells were derived. Video image analysis
      measurement identified quantitative differences in AR staining between the two
      antibodies, suggesting that this approach may provide a means of identifying
      receptor variants in prostate tumors. The AR staining measurements were analyzed
      by discriminant function analysis to assign individual cases to good and poor
      clinical outcome groups. AR staining features measured with a single antibody
      (e.g., amino-terminal) were sufficient to predict outcome following hormonal
      therapy in stage D2 patients (predictive value, 1.0), whereas all features of AR
      staining measured with both antibodies were required for the entire patient group
      (predictive value, 0.97). The principal discriminant in both patient groups
      contributing to the correct assignment of outcome was the mean intensity of AR
      staining per cell. These findings suggest that AR staining features measured by
      video image analysis have the potential to predict outcome in prostate cancer.

PMID- 7518352
TI  - Markedly increased amounts of messenger RNAs for vascular endothelial growth
      factor and placenta growth factor in renal cell carcinoma associated with
      angiogenesis.
AB  - The presence of mRNAs for vascular endothelial growth factor (VEGF) and a VEGF
      related protein, placenta growth factor (PIGF) was examined in 29 cases of renal
      cell carcinoma tissues and adjacent normal kidney tissues and in 4 human renal
      cell carcinoma cell lines. Northern blot analysis showed that 26 of 27
      hypervascular renal cell carcinoma tissues (96%) exhibited a markedly elevated
      level (3-13 fold) of VEGF mRNA compared to the adjacent normal kidney tissues.
      Even tumors of small size, whenever they were hypervascular, overexpressed VEGF
      mRNA. We also demonstrated that mRNA for PIGF was expressed in 21 of 23
      hypervascular renal cell carcinoma tissues (91%) but was not detected in the
      adjacent normal kidney tissues. Two hypovascular carcinoma tissues neither
      overexpressed VEGF mRNA nor had PIGF mRNA. VEGF mRNA was detected in four human
      renal cell carcinoma cell lines, while PIGF mRNA was not. There was no difference
      in the level of basic fibroblast growth factor mRNA between tumor tissues and
      normal kidney tissue, although our previous study demonstrated elevated basic
      fibroblast growth factor protein in the serum of renal cell carcinoma patients
      (K. Fujimoto et al., Biochem. Biophys. Res. Commun., 180: 386-392, 1991). Taken
      together, these results suggest that VEGF, PIGF, and basic fibroblast growth
      factor are cooperatively working to increase the angiogenesis in renal cell
      carcinoma in vivo.

PMID- 7518354
TI  - The CSF myelin basic protein in pediatric hydrocephalus.
AB  - Concentrations of myelin basic protein (MBP) in ventricular and lumbar
      cerebrospinal fluid (CSF) of 20 pediatric hydrocephalic patients were reviewed.
      Raised values were found to be particularly significant in children aged more
      than 1 year. Control measurements after shunt placement showed an important drop
      in the MBP concentration, which could therefore be considered a marker for
      correct functioning of the shunt. The dosage of MBP could play a role in
      assessing the activity of an hydrocephalic process. Preliminary data gained from
      monitoring of MBP in the lumbar CSF in posthemorrhagic neonatal hydrocephalus
      could yield further criteria for indication of a shunt operation.

PMID- 7518351
TI  - Insertion signal sequence fused to minimal peptides elicits specific CD8+ T-cell
      responses and prolongs survival of thymoma-bearing mice.
AB  - CD8+ T-lymphocytes (TCD8+) recognize minimal peptides of 8-10 residues which are
      the products of intracellularly processed proteins and are presented at the cell
      surface by major histocompatibility complex class I molecules. An important step
      in this process is the translocation of processed proteins from the cytosol
      across the endoplasmic reticulum membrane, mediated by transporter associated
      with antigen-processing proteins or alternatively by endoplasmic reticulum
      insertion signal sequences located at the NH2-terminus of the precursor
      molecules. We report here that the addition of an endoplasmic reticulum-insertion
      signal sequence at the NH2-terminus of TCD8+ epitopes from chicken ovalbumin
      (amino acids 257-264) or a naturally occurring tumor antigen expressed by the
      murine mastocytoma P815 (P1A amino acids 35-43) significantly enhanced the
      priming of specific TCD8+ in vivo. The signal sequence did not enhance peptide
      immunogenicity by merely increasing the hydrophobicity of the peptide, since
      ovalbumin amino acids 257-264 peptide with the signal sequence at its COOH
      terminus did not demonstrate enhanced efficacy. The signal sequence did not act
      as a helper epitope, since TCD8+ responses were not diminished in class II
      deficient transgenic mice or in mice depleted of CD4+ T-cells in vivo.
      Importantly, a single immunization with the fusion peptide significantly
      prolonged survival of mice challenged with E.G7OVA, a thymoma transfected with
      the complementary DNA of chicken ovalbumin.

PMID- 7518353
TI  - CD44H expression by human neuroblastoma cells: relation to MYCN amplification and
      lineage differentiation.
AB  - The human CD44 cell surface glycoprotein has been involved in a variety of
      functions including lymphocyte homing, extracellular cell matrix attachment, and
      tumor metastasis. Due to the alternative splicing of the single gene, a large
      family of different variants or isoforms is generated. Several reports have
      indicated an up-regulation of CD44 variant (v) isoforms in malignant process,
      conferring metastatic potential to non-metastatic cells. Neuroblastoma is a tumor
      characterized by an aggressive and metastatic behavior in advanced stages with
      amplification of the MYCN protooncogene. In this report we show that the CD44
      standard molecule is highly expressed in 100% of stage I-III, IVs neuroblastomas
      and ganglioneuromas but only in a subset of stage IV tumors. In contrast, no
      expression of CD44 was detected on MYCN amplified stage IV tumors, thus
      demonstrating a highly significant negative relationship between MYCN
      amplification and CD44 expression in neuroblastoma. The expression of CD44 on
      neuroblastoma cultured cell lines was not shown to be related to MYCN
      amplification but rather linked to the S-type, schwann/glial differentiation
      lineage. Immunochemical analysis of tumor samples with anti-CD44v3 and -v6
      antibodies and Northern blot analysis of mRNA from cell lines with probes
      spanning exons 4-10 did not reveal any expression of splice variants on
      neuroblastomas of all stages and cell lines, thus ruling out a major role of
      these isoforms in neuroblastoma progression and metastasis.

PMID- 7518355
TI  - RNA-RNA interactions in the spliceosome: unraveling the ties that bind.

PMID- 7518356
TI  - RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion
      and is homologous to yeast TORs.
AB  - The immunosuppressants rapamycin and FK506 bind to the same intracellular
      protein, the immunophilin FKBP12. The FKB12-FK506 complex interacts with and
      inhibits the Ca(2+)-activated protein phosphatase calcineurin. The target of the
      FKBP12-rapamycin complex has not yet been identified. We report that a protein
      complex containing 245 kDa and 35 kDa components, designated rapamycin and FKBP12
      targets 1 and 2 (RAFT1 and RAFT2), interacts with FKBP12 in a rapamycin-dependent
      manner. Sequences (330 amino acids total) of tryptic peptides derived from the
      245 kDa RAFT1 reveal striking homologies to the yeast TOR gene products, which
      were originally identified by mutations that confer rapamycin resistance in
      yeast. A RAFT1 cDNA was obtained and found to encode a 289 kDa protein (2549
      amino acids) that is 43% and 39% identical to TOR2 and TOR1, respectively. We
      propose that RAFT1 is the direct target of FKBP12-rapamycin and a mammalian
      homolog of the TOR proteins.

PMID- 7518357
TI  - Lack of circadian variation in the responsiveness of alpha 2-heteroreceptors
      regulating serotonin release.
AB  - We have previously shown that the circadian variation in 5-HT release is not the
      consequence of a variation in the activity of terminal 5-HT1B autoreceptors.
      However, recently identified alpha 2-adrenoceptors located on 5-HT nerve
      terminals may be important in regulating the release of 5-HT from serotonergic
      neurons. The sensitivity of hippocampal alpha 2-heteroreceptors to both agonist
      and antagonist was determined at different time points in the light:dark cycle of
      the rat. No significant circadian differences were evident in either the apparent
      pD2 values calculated for noradrenaline to inhibit potassium-evoked tritium
      efflux or in the apparent pA2 values calculated for phentolamine to antagonize
      the effect of noradrenaline. The corollary of the lack of a circadian rhythm in
      sensitivity to the alpha 2-heteroreceptor is that this receptor population will
      accurately reflect any circadian variation in noradrenaline release and in the
      available concentration of noradrenaline at the receptor sites.

PMID- 7518358
TI  - [A clinicopathologic study of 15 cases of collecting duct carcinoma of the
      kidney].
AB  - Fifteen cases of papillary adenocarcinoma of the kidney are presented. The
      lesions were polycystic in gross appearance. Histologically, they were subdivided
      into three types: papillary cystadenocarcinoma, papillary oncocytic
      cystadenocarcinoma and papillary mucinous cystadenocarcinoma.
      Immunohistochemically, the tumor cells demonstrated positive reactivity for high
      molecular weight keratin and glandular lumina membrane positivity for EMA, which
      support a collecting duct origin for the tumor. Most of the tumors were large
      (average diameter 9.6 cm) and invasion of perinephric tissues was observed in 80%
      of the cases, an indication of its aggressive behavior. As most of the tumors
      occurred in the medulla and invaded the collecting ducts, the clinical
      manifestations were different from those of renal cell carcinomas.

PMID- 7518360
TI  - Formation of DNA adducts in rat lung following chronic inhalation of diesel
      emissions, carbon black and titanium dioxide particles.
AB  - Exposure of rats to diesel emissions results in the development of lung tumors.
      The objective of this study was to determine whether the polycyclic aromatic
      hydrocarbons (PAHs), nitro-PAHs or other polycyclic organic matter adsorbed to
      diesel particles induces the formation of DNA adducts in the lung when compared
      to particles with little or no adsorbed organic matter. Rats were exposed to
      diesel emissions containing particles with over 30% solvent-extractable adsorbed
      organic matter and to particles with < 0.1% adsorbed organic matter (carbon black
      particles and TiO2). Wistar rats were exposed to diesel emissions (7.5 mg/m3) for
      2 months, 6 months and 2 years and for 2 years to carbon black (11.3 mg/m3) and
      TiO2 particles (10.4 mg/m3) to compare tumorigenic response and DNA adduct
      formation in the lung. Two versions of the 32P-postlabeling assay for the
      detection of DNA adducts were used to tentatively identify nitrated-amine or
      arylamine adducts formed relative to other nitro PAH based on the demonstrated
      sensitivity of these adducts to nuclease P1 treatment. Total adduct levels were
      determined for peripheral lung tissue DNA as detected in a diagonal radioactive
      zone. One major adduct which migrated outside this region (adduct 1) and a
      nuclease P1-sensitive adduct (adduct 2) were quantitated separately. Adduct 1
      increased significantly over time in the filtered air exposed animals but
      decreased markedly at the 2 year time points regardless of particle type,
      presumably as a result of adduct dilution through de novo cell synthesis or cell
      proliferation invoked in response to particle loading and/or effect on the
      endogenous synthesis or degradation of DNA reactive moieties. The nuclease
      sensitive adduct (adduct 2), possibly resulting from exposure to nitro-PAHs, was
      detected in diesel-exposed rats but was not detected in the rats exposed to TiO2
      and carbon black. No significant elevation in PAH-derived adducts, relative to
      the filtered air controls, was observed in the rodents exposed to diesel
      emission. Our data suggest that long-term contact with these particles may result
      in a cell proliferative response, enhanced degradation of I-compounds not related
      to cell proliferation, and/or synthesis of I-compounds, irrespective of the
      differences in organic content associated with the three particle types. This
      response may be an important factor in explaining the reported similarity in
      tumorigenic response in rodents exposed to diesel emissions, carbon black and
      TiO2 particles.

PMID- 7518359
TI  - The quinoline-3-carboxamide linomide inhibits angiogenesis in vivo.
AB  - Linomide (Roquinimex) has antitumor activity when given in vivo (but not when
      applied in vitro) that has been attributed to immune host mechanisms. Recent
      studies, however, suggest that Linomide may also possess antiangiogenic
      properties. The aim of the present study was to evaluate the antiangiogenic
      effect of Linomide using an intravital microscopic technique. Syngeneic
      pancreatic islets were isolated and implanted into the dorsal skinfold chamber of
      Syrian golden hamsters. This model allows detailed repeated in vivo observations
      and quantitative analysis of revascularization of pancreatic islet grafts. The
      neovascularization process of the islets is a highly reproducible phenomenon that
      is completed within about 2 weeks, resulting in a microvascular network very
      similar to that of islets in situ. The plasma concentration profile of Linomide
      following a single oral dose of the compound was determined. The elimination of
      Linomide was fast, the half-life being 2.6 +/- 0.2 h. Due to the short half-life,
      the hamsters were given Linomide twice a day. One group of animals (n = 9) was
      force-fed Linomide (100 mg/kg per day) from the day of implantation throughout
      the 2-week observation period, and the results were compared with those obtained
      in a nontreated control group (n = 7). At days 6, 10, and 14 after implantation,
      the neo-vasculature of the islets was examined. In the control group, 91% +/- 4%
      (mean +/- SEM) of the islets showed the first signs of angiogenesis at day 6,
      whereas in the Linomide-treated group the corresponding value was 48% +/- 12%. At
      days 10 and 14, the "take-rate" in the control group increased to 94% +/- 3% for
      day 0 and to 94% +/- 4% (n = 6) for day 14, whereas in the treated group the
      corresponding take-rate was 67% +/- 11% and 72% +/- 12%, respectively. The
      functional capillary density in the control group at days 6, 10, and 14 was 223
      +/- 17,348 +/- 29, and 495 +/- 29 cm-1, respectively, and that in the Linomide
      treated group was 91 +/- 28, 181 +/- 43, and 229 +/- 47 cm-1, respectively. These
      results demonstrate that Linomide suppresses the neovascularization of the islet
      grafts by both delaying the onset of and reducing the percentage of islets
      displaying angiogenesis as well as by decreasing the rate of proliferation of
      capillary endothelium of the revascularized islets.

PMID- 7518363
TI  - Diminished transient outward currents in rat hypertrophied ventricular myocytes.
AB  - Action potential duration is prolonged in ventricular hypertrophy induced by
      sustained pressure overload. Since the transient outward current (I(to)) is a
      major factor for determining action potential duration in rat ventricular cells,
      we used patch-clamp techniques to compare the characteristics of I(to) in normal
      and hypertrophied left ventricular cells of the rat. Left ventricular pressure
      overload was induced by partial ligation of the abdominal aorta for 4 to 6 weeks
      before study. Age-matched normal rats served as controls. Pressure overload
      increased the heart weight-to-body weight ratio by 47.7%. I(to) was significantly
      smaller in hypertrophied cells than in normal cells (20.0 +/- 1.3 versus 31.0 +/-
      2.1 pA/pF, respectively, at a test potential of +60 mV; P < .001). There were no
      differences in the steady-state inactivation, the inactivation time course, and
      the time course of recovery from inactivation between normal and hypertrophied
      cells. At the single-channel level, there were no differences in the unitary
      current amplitude of the single I(to) channel between normal and hypertrophied
      cells, and the slope conductance was 13.7 picosiemens in normal cells and 13.4
      picosiemens in hypertrophied cells. The maximum open-state probability, which was
      estimated from the ratio of the peak of the ensemble-averaged currents to the
      single-channel current amplitude, was similar for normal and hypertrophied cells
      (0.66 +/- 0.03 and 0.69 +/- 0.04, respectively, at a test potential of +40 mV; P
      = NS). We conclude that diminished I(to) contributes to action potential
      prolongation in hypertrophied ventricular cells from pressure-overloaded rat
      hearts. Reduced I(to) channel density may be responsible for the diminished whole
      cell I(to).

PMID- 7518364
TI  - Beta-adrenergic stimulation disassembles microtubules in neonatal rat cultured
      cardiomyocytes through intracellular Ca2+ overload.
AB  - Catecholamine cardiotoxicity is attributable in part to Ca2+ overload. To test
      whether the cytoskeletal structures of microtubules in cardiomyocytes are
      reversibly injured by catecholamine through excessive Ca2+ influx, morphological
      changes in the microtubules of neonatal rat myocytes were studied by
      immunohistochemical technique during exposure to norepinephrine (NE). In intact
      myocytes, microtubules appeared as a filamentous network throughout the cytoplasm
      and around the nucleus. NE exposure (10 mumol/L) for > 30 minutes elicited
      microtubular disassembly in a duration-dependent fashion without any irreversible
      change in sarcomere structure, and this abnormality recovered within 24 hours
      after cessation of stimulation. Microtubular disruption scores obtained by
      semiquantitative assessment were significantly increased in a dose-dependent
      manner (10.8 +/- 4.0 in the control condition, 23.4 +/- 4.7 at 60 minutes with 10
      mumol/L NE), whereas they were significantly attenuated by pretreatment with
      propranolol (100 mumol/L; score, 11.8 +/- 3.3) but not with phentolamine (100
      mumol/L; score, 26.4 +/- 4.8). Isoproterenol (1 mumol/L) and denopamine (10
      mumol/L) mimicked the effects of NE, but phenylephrine did not, indicating that
      NE-induced microtubular disassembly is mediated by beta 1-adrenergic receptor
      stimulation. This beta-adrenergic receptor-mediated insult was significantly
      attenuated by a decrease in Ca2+ concentration in the medium from 2 to 0.5 mmol/L
      and by pretreatment with diltiazem (1 mumol/L). In contrast, microtubular
      disassembly was induced by an increase in Ca2+ concentration in the medium and an
      administration of the Ca2+ ionophore A23187, even without beta-adrenergic
      receptor stimulation. Involvement of intracellular hypoxia and activation of
      Ca(2+)-calmodulin-dependent kinase or Ca(2+)-dependent neutral protease were
      excluded from possible mechanisms; however, inhibition of tubulin polymerization
      by excessive Ca2+ influx during beta-adrenergic receptor stimulation may be
      primarily involved. We conclude that microtubular structures that support
      cellular integrity are reversibly injured by beta-adrenergic receptor stimulation
      through excessive Ca2+ influx.

PMID- 7518362
TI  - Nitric oxide-mediated effects of interleukin-6 on [Ca2+]i and cell contraction in
      cultured chick ventricular myocytes.
AB  - Cytokines have significant roles in some cardiovascular disorders, but direct
      myocardial effects of cytokines remain to be elucidated. In the present study, we
      examined both the early and delayed effects of interleukin-6 (IL-6) on cultured
      chick embryo ventricular myocytes. Exposure of these cells to human recombinant
      IL-6 significantly decreased peak systolic [Ca2+]i (71.0 +/- 0.6% of the control
      value) and the amplitude of cell contraction (66.0 +/- 7.4% of the control value)
      within a few minutes. Pretreatment with NG-monomethyl-L-arginine (L-NMMA) or
      methylene blue completely inhibited the IL-6-induced early changes. Subsequent
      addition of L-arginine reversed the effects of L-NMMA. The levels of cGMP were
      significantly increased after 30 minutes of exposure to IL-6 (134.4 +/- 9.1% of
      the control value). Pretreatment with L-NMMA or EGTA significantly inhibited the
      IL-6-induced early elevation of cGMP. These results suggest that IL-6 acutely
      decreases intracellular Ca2+ transients and depresses cell contraction by nitric
      oxide (NO)-cGMP-mediated pathway. Therefore, IL-6 may enhance the Ca(2+)
      dependent constitutive NO synthase activity in cardiac myocytes. On the other
      hand, 24-hour exposure to IL-6 also increased the levels of cGMP (159.0 +/- 22.8%
      of the control value) regardless of pretreatment with EGTA. These delayed
      increases in cGMP were also shown to be coupled with decreases in intracellular
      Ca2+ transients and the amplitude of cell contraction. Thus, IL-6 may induce
      Ca(2+)-independent NO synthase in cardiac myocytes. Together with the previous
      reports that have suggested the possible roles of IL-6 in myocardial stunning or
      endotoxic shock, this negative inotropic effect of IL-6 may contribute to these
      clinical settings.

PMID- 7518361
TI  - Differential regulation of acidic and basic fibroblast growth factor gene
      expression in fibroblast growth factor-treated rat aortic smooth muscle cells.
AB  - The acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor
      (bFGF) proteins are potent vascular smooth muscle cell (SMC) mitogens that are
      expressed by endothelial cells and SMCs in vivo. Overexpression of these proteins
      in transfected cell lines can result in autocrine transformation; therefore, the
      precise control of fibroblast growth factor gene expression in the vessel wall
      may be an important mechanism regulating vascular cell growth. In the present
      study, we demonstrate that bFGF can induce bFGF mRNA expression, but not aFGF
      mRNA expression, in serum-starved rat aortic SMCs. bFGF autoinduction is maximal
      at 4 hours, requires de novo RNA and protein synthesis, and is mediated
      predominantly by a protein kinase C-dependent signaling pathway. Furthermore,
      aFGF treatment of rat SMCs also increases bFGF mRNA and protein expression;
      however, aFGF mRNA levels are only slightly modulated. These results suggest that
      the local release of aFGF or bFGF within the vessel wall could promote a
      prolonged period of elevated bFGF synthesis. This, in turn, could be of
      importance in the SMC hyperplasia that occurs in response to vascular injury and
      during atherosclerotic plaque formation.

PMID- 7518365
TI  - Altered pulmonary microvascular reactivity to norepinephrine in canine pacing
      induced heart failure.
AB  - Pulmonary hypertension in congestive heart failure causes medial hypertrophy in
      pulmonary vessels and thickening of the endothelial basement membrane. In this
      study, the functional consequences of such pulmonary vascular adaptations were
      evaluated. Heart failure was induced in dogs by rapid ventricular pacing (240
      beats per minute) for 28 days, at which time left ventricular shortening fraction
      was decreased by 57% compared with that at baseline. Lung lobes from paced (n =
      56) and control dogs (n = 68) were isolated and perfused with autologous blood.
      Total, arterial (Ra), and venous (Rv) vascular resistances were significantly
      increased and vascular capacitance decreased in lobes from paced animals compared
      with controls. Increments in Ra and Rv after intra-arterial boluses of
      norepinephrine were measured before and after sequential addition of the alpha 1-
      and alpha 2-receptor antagonists prazosin (16 mumol/L) and yohimbine (0.1
      mumol/L) in the presence or absence of propranolol (5 mumol/L). Norepinephrine (1
      to 40 micrograms) had little effect on Ra in the absence of propranolol, a
      pattern that persisted in control lobes after propranolol. However, when lobes
      from paced animals were pretreated with propranolol, norepinephrine increased Ra,
      Rv was increased after norepinephrine in control lobes, an effect that was
      enhanced in the paced group. In both groups, the increment in Rv was greater
      after propranolol. Irrespective of propranolol pretreatment, prazosin
      significantly attenuated, if not abolished, the response to norepinephrine. The
      enhancement in venous vascular reactivity in lobes from paced animals remained
      when venous pressure was elevated to 20 cm H2O. In control lobes under conditions
      of elevated tone or when endothelium-dependent relaxing factor was blocked,
      responses to norepinephrine did not mimic those observed in the paced group.
      Microvascular permeability, as measured by the capillary filtration coefficient,
      was not altered in the paced group. We conclude that the pulmonary adaptations to
      4 weeks of rapid ventricular pacing include functional changes in pulmonary
      hemodynamics and vascular reactivity but not in microvascular permeability.

PMID- 7518367
TI  - Characterization of anti-peptide antibodies directed against an extracellular
      immunogenic epitope on the human alpha 1-adrenergic receptor.
AB  - A synthetic peptide corresponding to amino acids 192-218 of the second
      extracellular loop of the human alpha 1A-adrenergic receptor was used to raise
      antibodies in rabbits. Affinity-purified antibodies specifically recognized main
      bands with a molecular weight of about 68, 40 and 37 kD on the electrotransferred
      membrane proteins of rat ventricle membranes. The incubation of these antibodies
      with rat myocardial membranes resulted in a decrease in the number of binding
      sites for the specific radiolabelled alpha 1-antagonist prazosin. These
      antibodies were also able to mimic the effects of agonist stimulation as
      demonstrated by a positive chronotropic effect on cultured cardiomyocytes. These
      results constitute the first immunochemical evidence of the presence of both the
      A and B subtypes of the alpha 1-adrenergic receptor in the heart. They also
      confirm that the second extracellular loop of the alpha 1-adrenergic receptors is
      an immunologically and functionally important domain.

PMID- 7518370
TI  - Surgery for advanced ovarian cancer.

PMID- 7518368
TI  - The immunomodulatory activity of human amniotic fluid can be correlated with
      transforming growth factor-beta 1 (TGF-beta 1) and beta 2 activity.
AB  - The role of alphafetoprotein (AFP) in the immunomodulatory activity of amniotic
      fluids (AF) from normally progressing human pregnancy (weeks 14-16) was
      investigated. A panel of 42 AF (25% v/v) reduced significantly
      phytohaemagglutinin (PHA)-induced peripheral blood mononuclear cell (PBMC)
      proliferation in serum-free cultures with a mean per cent inhibition of 68.4 +/-
      5.5%. In contrast, AFP preparations, with one exception (U.AFP), failed to
      display inhibitory activity. Pretreatment of AF with anti-TGF-beta 1 and beta 2
      antibodies used alone resulted in the mean per cent loss of inhibition of 33.1 +/
      3.9% and 52.3 +/- 7.5%, respectively. A summative loss of AF-mediated inhibition
      was detected when anti-TGF-beta 1 and beta 2 antibodies were used in combination,
      but immunomodulation was rarely abolished 100% by this treatment. Anti-TGF-beta 2
      antibody treatment, unlike anti-TGF-beta 1 antibody treatment, reversed the
      inhibitory activity of U.AFP. The amount of TGF-beta 1 and beta 2 contained in
      human AF was studied by growth inhibition of Mv1 Lu cells. The mean levels of TGF
      beta 1 and beta 2 in AF were 11 +/- 0.9 U/ml and 2.3 +/- 0.4 U/ml, respectively,
      which corresponds with a mean per cent inhibition of 49 +/- 4.7%. U.AFP also
      significantly inhibited Mv1 Lu cell growth. To investigate the mechanism of AF
      mediated inhibition, the effect of AF and AFP on IL-2 production by concanavalin
      A (Con A)-stimulated PBMC blasts was determined by the CTLL-2 cell bioassay. IL-2
      production was reduced 55.5% in AF-treated blasts and 61% in U.AFP-treated blasts
      compared with controls. Our findings indicate that the immunomodulatory activity
      of human AF can be correlated with TGF-beta 1 and beta 2 and not with AFP, the
      inhibitory activity of U.AFP preparation reflecting copurifying TGF-beta 2
      activity.

PMID- 7518366
TI  - Altered expression of CD11/CD18 on the peripheral blood phagocytes of patients
      with tuberculosis.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis, is characterized by
      granulomatous lesions made up of epithelioid cells, giant cells and mononuclear
      leucocytes. Cell-cell adhesion is important in granuloma formation and in the
      leucocyte migration which accompanies it. We have recently shown increased
      expression of the adhesion molecules CD11/CD18 (LeuCAMs, beta 2 integrins) on
      peripheral blood leucocytes from patients with sarcoidosis (Shakoor & Hamblin,
      1992). Here we have studied the expression of CD11/CD18 and CD29 (VLA beta 1
      integrin) on the peripheral blood leucocytes of 10 TB patients by flow cytometry.
      The density (expressed as mean fluorescence intensity) of CD11b on monocytes and
      polymorphs was increased (P < 0.005), as was CD11c (P < 0.005) and CD18 (P <
      0.05) on polymorphs. CD11a expression was significantly reduced on polymorphs (P
      < 0.05). No differences were found in the expression of CD29, the percentages of
      cells expressing any molecule and, in contrast to sarcoidosis, the density of any
      molecule on lymphocytes. Although the cytokine tumour necrosis factor (TNF) has
      been implicated in the process of up-regulation, an ELISA for TNF failed to
      detect significant levels in plasma. The results suggest increased peripheral
      phagocyte CD11/CD18 expression is a feature of TB, which may contribute to the
      pathological processes involved.

PMID- 7518369
TI  - Inhibition of HIV replication by CD8+ T cells correlates with CD4 counts and
      clinical stage of disease.
AB  - We sought to evaluate the relationship of CD8+ T cell-mediated inhibition of
      autologous HIV replication in vitro to disease stage in HIV+ individuals.
      Depletion of CD8+ T cells from peripheral blood lymphocytes of 16 HIV+ subjects
      increased the percentage of virus-producing cultures from 56% to 81%. CD4+ T
      cells were purified from 52 HIV+ individuals and cultured alone or in the
      presence of autologous CD8+ T cells. In 13 (25%) subjects HIV replication was
      only detected in the absence of CD8+ T cells (inhibition positive); in 26 (50%)
      viral replication occurred both in the absence and presence of CD8+ cells
      (inhibition negative). In the remaining 13 (25%) subjects, CD8+ T cell-mediated
      inhibitory activity could not be evaluated because stimulation of their purified
      CD4+ T cells did not result in p24 production. In some virus culture-negative
      individuals, the inability to demonstrate HIV replication was due to the presence
      of low numbers of CD8+ T cells that co-purified with CD4+ T cells. Detection of
      inhibitory CD8+ T cells was associated with significantly higher CD4 counts and
      better clinical status compared with inhibition-negative subjects. These results
      demonstrate that CD8+ T cell-mediated inhibition of HIV replication correlates
      with disease stage, and thus may play a role in preventing disease progression.
      CD8+ T cells did not inhibit autologous HIV replication across a semipermeable
      membrane. Further, the ability of CD8+ T cells to prevent HIV replication did not
      correlate with lysis of autologous CD4+ T cells. Thus, CD8+ T cells inhibited
      autologous HIV replication in vitro through a contact-mediated non-lytic
      mechanism.

PMID- 7518371
TI  - Expression of non-glial intermediate filament proteins in gliomas.
AB  - Non-glial intermediate filament (IMF) proteins, as well as glial fibrillary
      acidic protein (GFAP) and vimentin, were studied by immunohistochemistry in 24
      gliomas including low grade astrocytoma, pleomorphic xanthoastrocytoma,
      anaplastic astrocytoma, glioblastoma, oligodendroglioma, ependymoma and
      ependymoblastoma, which were fixed in ethanol and embedded in paraffin.
      Cytoskeletal elements isolated from two glioblastomas were examined with
      immunoblot analysis. All tumors had GFAP-positive neoplastic cells and vimentin
      was also found in all the tumors except one oligodendroglioma. Twenty-three
      gliomas were immunostained with anti-desmin polyclonal antibody (DM-P), but anti
      desmin monoclonal antibody reacted to only one glioblastoma. DM-P might
      crossreact with GFAP and vimentin. Cytokeratin expression was investigated with
      six antibodies. Twenty gliomas (83%) were positive for the antibody against
      epidermal keratin (CK-SE), however positive immunoreactivity varied from 58 to 8%
      with other cytokeratin antibodies. With the Western blot method, CK-SE had
      protein bands at 53 and 60-66 kDa. Neurofilament was expressed in one pleomorphic
      xanthoastrocytoma, one anaplastic astrocytoma, one glioblastoma and one
      ependymoblastoma. Expression of nonglial IMF proteins were observed in 21 tumors
      (88%), and coexpression of 4 or 5 classes of IMF proteins in 3 tumors (13%). We
      conclude that, in addition to GFAP and vimentin, gliomas express several types of
      non-glial IMF proteins.

PMID- 7518372
TI  - In situ measurement of fluorescein release by collagen shields in human eyes.
AB  - Fluorescein (F) and FITC Dextran (FD; MW 4400) have been used as inert analogs of
      active drugs to examine the factors controlling the rate of loss of drugs from
      collagen shields in vivo. The diffusion constants in the shield (120 microns
      thick) determined from in vitro release experiments were found to be 0.42 x 10(
      6) for F and 0.16 x 10(-6) cm2/sec for FD at 34 degrees C and these values
      correspond to 0.7 and 0.27 min-1 rates of loss for the exponential parts of their
      release. In the eyes of 6 subjects, the F loaded shields lost the dye at an
      average rate of 0.016 min-1 initially, increasing to 0.026 min-1 at the end of an
      hour. Somewhat higher values were noted with FD and were attributed to variations
      of manufacturing of the shields. Comparing the rates of loss in in vitro and in
      vivo, it is clear that the latter is not controlled by the rate of diffusion in
      the shield, but is limited by the rates of tear secretion and flow over the
      surfaces of the shield. The penetration of F into the anterior chamber from a
      series of four drops applied 12 min apart was compared with that from a shield
      soaked in the drop solution to determine the enhancement in the bioavailability.
      This showed that the shield increased the penetration into the eye by about 16
      times over that from a single drop. However, the rate of loss of F from the
      shield in vivo is only about 8 times slower than that from a drop instilled in
      the eye.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518373
TI  - Relationship between the characteristics of immunopathological expression of
      hepatitis C virus antigen and hepatocytic injury.
AB  - Biopsied liver tissues from 352 cases were tested for hepatitis C virus (HCVAg)
      with improved PAP immunohistologic chemical method. Furthermore, corresponding
      seroantibody to hepatitis C virus was also tested. The total HCVAg positive rate
      was 9.1%. The HCVAg positive rate in chronic persistent hepatitis (CPH) was 5%.
      The HCVAg positive rate in chronic active hepatitis (CAH) was 11.2%. The HCVAg
      positive rate raised gradually along with the severity of hepatocytic injury.
      HCVAg may be seen in necrotic liver cells exfoliating into the liver sinus,
      indicating a close relationship between HCVAg and hepatocytic injury. Expression
      of HCVAg was mostly of the nucleus type in CPH cases and was mostly of the plasma
      type in CAH cases. The periphery of nucleus type-expressed positive cells
      generally had no marked inflammatory cell infiltration. The periphery of plasma
      type-expressed positive cells had a certain amount of inflammatory cell
      infiltration. Along with the severity of hepatocytic injury, HCVAg expressed
      itself in a positive correlation according to the nucleus and plasma types. The
      HCVAg positive cells were located mostly in the lobular peripheral band and
      rarely located in the venoperipheral band. It was possible that this had some
      relation with the lobular microcirculation of blood and blood supply. In this
      study, there was no obvious correlation between the HCVAg positive rate in
      hepatic tissues and the anti-HCV positive rate in sera. Neither the patients with
      HCVAg positive liver tissues nor the patients with seropositive anti-HCV had any
      history of blood transfusion and the use of blood products.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7518374
TI  - [A clinical analysis of 117 cases of acute arsenic poisoning].
AB  - 117 cases of acute arsenic poisoning, caused by ingestion of food contaminated by
      As2O2, presented with abdominal pain, vomiting, nausea and diarrhea. The average
      level of urinary arsenic was 3.926 mg/L. The incidence of neuritis, poisoning
      hepatopathy and abdominal ECG was respectively 7.7%, 32.54%, 35.9%. All the cases
      recovered after oral or parenteral administration of dimecapto succinate (DMS) in
      six weeks. DMS is the drug of choice in the treatment of arsenic poisoning.

PMID- 7518375
TI  - [The effects extracorporeal circulation and open heart surgery on cardiovascular
      regulate peptide].
AB  - Serum endothelin (ET), calcitonin gene-related peptide (CGRP), neurotensin (NT)
      and substance-P (SP) were determined in 15 patients undergoing open heart
      surgery. The ET content was higher before operation that during and after
      operation (P < 0.01). After heart recovery by open circulation, the ET content
      was lowest. Returning to ICU and 24 hours after operation, the ET content was
      elevated but still lower than that before operation. The CGRP content was not
      changed obviously during CPB but higher than that before and during operation (P
      < 0.05). The NT content was not changed during CPB but was higher after returning
      to ICU. It returned to normal 24 hours postoperatively. The SP content increased
      significantly during CPB, and returned to normal after returning to ICU and 24
      hours postoperatively. The reasons and clinical significance of these changes
      were discussed.

PMID- 7518376
TI  - [Endoscopic retrograde biliary drainage for malignant obstructive jaundice].
AB  - This paper reports 19 cases of malignant obstructive jaundice treated by
      endoscopic retrograde biliary drainage (ERBD). Since 1989, ERBD is a palliative
      treatment of inserted into the obstructed bile duct by endoscopy. This method can
      efficiently relieve biliary obstruction. Elimination jaundice reduces some
      discomforts such as irritating pruritus. It also increases the appetite and
      improve patient's general physical condition. Temporary preoperative
      decompression of the bile ducts in seriously jaundiced patients should result in
      a significant reduction postoperative morbidity and mortality. There were 9
      patients of this group who underwent operation after a short period of drainage,
      These patients weren't found any postoperative complication. ERBD also be used
      for palliative decompression of the bile duct in cases of inoperable cancer. The
      method was carried out in 7 inoperable patients of this group. Results were
      satisfactory.

PMID- 7518377
TI  - Measurement by flow cytometry of genomic AT/GC ratio and genome size.
AB  - Flow cytometry with the AT-specific fluorochrome Hoechst 33258 (HO) and the GC
      specific fluorochrome olivomycin (OM) was used for measurement of base pair
      specific DNA content in 20 species of vertebrates. The results were found to be
      in good correlation with the biochemical literature on base pair frequencies (r =
      0.972, P < 1 x 10(-8). This correlation allows one to determine the percent of
      GC/AT-pairs and genome size from flow cytometric data. The genome sizes obtained
      were compared with the literature data on flow cytometric genome size values
      determined with the use of propidium iodide (PI) that is usually believed to be
      non-base pair specific. The results were found to be in general agreement;
      however, the previously reported slight GC-preference of PI is confirmed. The
      optimal conditions for flow cytometry of AT/GC ratio and genome size with the use
      of OM and HO are discussed. The approach can be useful for research in ecology,
      fisheries science, species conservation, and other environmental studies as a
      tool for rapid survey of a vast array of specimens.

PMID- 7518378
TI  - Enumeration of CD34+ hematopoietic stem cells for reconstitution following
      myeloablative therapy.
AB  - The CD34+ cell fraction of bone marrow and blood contains the hematopoietic stem
      cells required for marrow reconstitution following myeloablative therapy. Because
      they are present in small numbers, accurate quantification is often difficult. We
      have developed a reproducible and sensitive flow cytometric method for CD34+
      enumeration of both bone marrow harvests and peripheral blood stem cell
      collections. The total numbers of harvested cells are enumerated by particle
      counting. A measured aliquot is stained with two FITC-labeled anti-CD34
      antibodies, one directed against 8G12 and the other against QBend epitope. To
      eliminate cells committed to mature lineages (lin+), the suspension is
      counterstained with a cocktail of PE-labeled antibodies including CD3 (T cells),
      CD19 (B cells), CD11b (neutrophils), and CD14 (monocytes). Particles < 6 microns
      in diameter are excluded by use of a standard bead gate. Regions are established
      using unstained U937 cells to set the vertical axis and PE stained U937 cells for
      the horizontal axis. Because of the low numbers of CD34+ cells, 20,000
      events/sample are analyzed. Dilutions of KG-1A tumor cells (CD34+) in U937 cells
      showed a threshold of detection of 0.1% CD34+lin- cells. Duplicate samples varied
      by < 10%. Initial studies indicate that this procedure can be reliably used to
      measure CD34+lin- cells in blood, pheresis products, and bone marrow harvests.
      This CD34 enumeration procedure should result in increased consistency in
      enumerating this stem cell population.

PMID- 7518379
TI  - [Tumor microvascular bed and its reactivity to vasoactive agents: measurement of
      tissue blood flow and patho-morphological study].
AB  - Structural characteristics of tumor microvascular bed and its reactivity to
      vasoactive agents were studied by histological and ultrastructural examination
      and tissue blood flow measurement. The results showed that newly formed vessels
      in the tumor tissue consisted of a single layer of endothelial cells with multi
      layer basement membranes and a few pericytes. Smooth muscle cells and nerve
      endings were absent. The tissue blood flow in highly proliferative parts of
      tumors was relatively constant and not influenced by tumor size, even though the
      distribution of neovasculature in tumor tissue was very uneven in distribution.
      The only vasoactive agent which can selectively increase the tumor blood flow was
      angiotensin II, whereas other adrenergic vasoconstrictors did not show this
      action.

PMID- 7518380
TI  - [Hereditary persistence of alpha-fetoprotein].
AB  - A proband with persistently elevated AFP levels ranging between 21-129 ng/ml with
      median of 90 ng/ml has been found and observed for 1 year. Family studies have
      revealed that his father had had persistent AFP elevation for 4 years, ranging
      from 46 to 198.2 ng/ml, with median level of 93 ng/ml. His brother also has
      elevated AFP level. However, his mother, paternal uncle and paternal aunt have
      normal AFP level. Clinical examinations and laboratory tests have shown that AFP
      elevations are not associated with primary hepatocellular carcinoma, hepatitis,
      or other malignancies. We believe that such AFP persistency is of hereditary
      nature. To our knowledge, this is the first family of hereditary AFP persistence
      reported in China and the fourth one reported in the world literature.

PMID- 7518381
TI  - Effects of fibroblast growth factor on type I 5'-deiodinase in FRTL-5 rat thyroid
      cells.
AB  - In the present study, we used FRTL-5 cells to study the effects of fibroblast
      growth factors (FGFs) on 5'-deiodinase (5'D) activity and messenger RNA (mRNA)
      levels. In FRTL-5 cells deprived of TSH for 7 days, type I 5'-deiodinase (5'D-I)
      activity decreased to low, but detectable levels. Incubation of cells with acidic
      and basic FGFs significantly decreased 5'D-I activity below the basal levels.
      After 7 days of TSH deprivation, the addition of TSH (100 microU/ml) to the
      medium for 3 days resulted in an increase in 5'D-I activity. This TSH-induced
      increase in 5'D-I activity was blocked by the FGFs in a dose-dependent manner.
      Kinetic analysis revealed that both acidic and basic FGFs decreased the maximum
      velocity of 5'D-I activity in the presence or absence of TSH, without any
      significant effect on the Km of enzyme binding. HPLC analysis of the products of
      the 5'D-I assay revealed that there was no sequential deiodination of rT3.
      Incubation of FRTL-5 cells with acidic or basic FGF did not affect basal cAMP
      concentrations, nor did they block the TSH-induced rise in cAMP. However, acidic
      and basic FGFs inhibited forskolin- and (Bu)2cAMP-induced increases in 5'D-I
      activity. Incubation of FRTL-5 cells with TSH, (Bu)2cAMP, and forskolin increased
      5'D-I mRNA levels. Incubation of FRTL-5 cells with acidic and basic FGFs
      decreased steady state 5'D-I mRNA levels and blocked the TSH-, forskolin-, and
      (Bu)2cAMP-induced increases in 5'D-I mRNA. In conclusion, we have demonstrated
      that FGFs inhibit 5'D-I activity and mRNA levels in FRTL-5 cells in the presence
      or absence of TSH. The inhibitory effect of FGFs on 5'D-I in FRTL-5 cells is
      mediated through either a cAMP-independent pathway or pathways distal to the
      generation of cAMP. The present data together with the identification of FGF in
      the thyroid gland suggest that FGF may play a physiological role in the
      regulation of thyroid hormone secretion.

PMID- 7518384
TI  - Immunohistochemical localization of insulin-like growth factor-II (IGF-II) and
      IGF-binding protein-2 during development in the rat brain.
AB  - The insulin-like growth factors (IGF-I and IGF-II) are peptide growth factors
      with both growth-promoting and insulin-like activities. In the nervous system,
      the expression of both IGF-I and IGF-II messenger RNAs (mRNAs) is developmentally
      regulated, with IGF-I expression highest during puberty, and IGF-II levels
      peaking during the perinatal period. The IGFs interact with and are modulated by
      a group of six binding proteins, the IGF-binding proteins (IGFBP-1 to IGFBP-6).
      IGFBP-2 mRNA is most prevalent in the nervous system, where, like IGF-II, its
      expression correlates with a period of brain growth. In the current study, cells
      containing IGF-II and IGFBP-2 were identified within the developing nervous
      system of the rat on embryonic day 12 (E12), E14, E18, and postnatal day 1 and in
      the adult. IGF-II immunoreactivity was detected within the mesenchymal core of
      the choroid plexus at all ages examined and was also observed in the developing
      leptomeninges. IGF-II appeared transiently in the central nervous system in
      presumptive glia of the hippocampus and medial basal hypothalamus and in a small
      population of neurons in the brain stem. IGFBP-2 was consistently observed in the
      epithelium of the choroid plexus as well as in the epithelia of the developing
      otic and olfactory placodes. While these results confirm the developmental
      expression of IGF-II and IGFBP-2 mRNA in the central nervous system,
      discrepancies exist between these data and those using molecular techniques. This
      may be due in part to differential sites of IGF-II and IGFBP-2 production
      compared to sites of action.

PMID- 7518383
TI  - Local administration of recombinant human interleukin-1 beta in the rat
      hippocampus increases serotonergic neurotransmission, hypothalamic-pituitary
      adrenocortical axis activity, and body temperature.
AB  - In this study, we equipped rats with a microdialysis probe in the hippocampus,
      which enabled stress-free intrahippocampal administration of recombinant human IL
      1 beta (hIL-1 beta). Perfusion of the probes was conducted with a Ringer's
      solution containing 0.1 or 1.0 microM hIL-1 beta or without hIL-1 beta, usually
      for 6 h. Time-dependent changes in serotonergic neurotransmission and
      hypothalamic-pituitary-adrenocortical activity were simultaneously monitored by
      measuring serotonin [5-hydroxytryptamine (5-HT)], 5-hydroxyindoleacetic acid, and
      corticosterone concentrations in the dialysates. In control rats, there was a
      clear relationship between extracellular 5-HT concentrations in the hippocampus
      and behavioral activity. Extracellular 5-HT levels were up to twice as high in
      behaviorally active rats compared to those in resting or sleeping animals.
      Intrahippocampal administration of hIL-1 beta markedly increased extracellular 5
      HT concentrations in the hippocampus and induced a significant decrease in
      behavioral activity, thereby uncoupling the parallelism between changes in 5-HT
      and changes in behavioral activity observed in control rats. Perfusion with 0.1
      microM hIL-1 beta, but not with 1 microM hIL-1 beta, produced a decrease in 5
      hydroxyindoleacetic acid levels, followed by a return to preinfusion levels.
      Moreover, intrahippocampal administration of hIL-1 beta increased hypothalamic
      pituitary-adrenocortical axis activity, as evidenced by marked increases in both
      plasma ACTH and plasma and dialysate corticosterone levels. In addition, a rise
      in body temperature by approximately 2 C was observed at time points at which the
      effects of hIL-1 beta on 5-HT and corticosterone levels were (near-)maximal. hIL
      1 beta-treated rats displayed typical characteristics of sickness behavior, such
      as immobility, piloerection, and a curled-up body posture. Most importantly, no
      effects were found either with heat-inactivated hIL-1 beta or when hIL-1 beta was
      administered via a probe implanted in the neocortex. Based on these results, we
      postulate that the hippocampal IL-1 system may play an important role in the
      coordination of neuroendocrine, autonomic, and behavioral responses after an
      immune challenge.

PMID- 7518382
TI  - Growth hormone (GH) deprivation induced by passive immunization against rat GH
      releasing factor does not disturb the course of sexual maturation and fertility
      in the female rat.
AB  - The importance of normal GH secretion for the onset of sexual maturation is a
      subject of controversy. Also, the need to achieve a minimal body size or body fat
      content has been postulated to be of importance for determining the timing of the
      onset of puberty. To evaluate the importance of GH secretion on the onset of
      sexual maturation in the female rat, GH deprivation has been induced by treating
      prepubertal rats with antirat GRF serum to passively immunize these animals
      against GRF. Chronic administration of anti-GRF serum produced in all series an
      impressive reduction in growth rate (from 5 to 2 g/day), resulting in a body
      weight averaging 50-60% the normal value at 50 days of life. Despite this deficit
      in growth, sexual maturation, as established by vaginal opening and first estrous
      cycles, occurred at the normal age in three of four series of rats; in one
      series, however, sexual maturation was delayed by 4 days, but thereafter, all
      parameters indicated that the gonadotropic axis was normally activated. In one
      series, fertility was tested at 59 days of age in females with a body weight
      corresponding to 51% of the control weight; these females conceived and delivered
      a reduced number of pups (9.4 +/- 0.7 instead of 14.2 +/- 0.8 in control dams),
      but the pups were of normal size. In a second experimental approach, the effect
      of GH deprivation was evaluated in a model of late sexual maturation obtained by
      severe food restriction followed by a switch to ad libitum feeding. Severe food
      restriction initiated at approximately 28 days, when the body weight was 75 g,
      drastically reduced the growth rate and completely prevented sexual maturation. A
      switch to ad libitum feeding at 50 days provoked an important compensatory growth
      and the occurrence of sexual maturation 4 days later. Passive immunization
      against GRF during this recovery phase did reduce the growth rate, but did not
      delay sexual maturation. Plasma insulin-like growth factor-I (IGF-I) secretion
      was very low in food-restricted rats and in each situation with induced GH
      deprivation. During food restriction, plasma IGF-binding protein-3 (IGFBP-3) and
      to a lesser extent IGFBP-1 were decreased, and IGFBP-2 was increased; after
      switching to ad libitum feeding, plasma levels of IGFBP-2 normalized, but levels
      of IGFBP-1 and IGFBP-3 remained low in the face of normalized plasma IGF-I
      levels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7518385
TI  - Reduction of insulin-like growth factor-I (IGF-I) in protein-restricted rats is
      associated with differential regulation of IGF-binding protein messenger
      ribonucleic acids in liver and kidney, and peptides in liver and serum.
AB  - To investigate the influence of the insulin-like growth factor binding-proteins
      (IGFBPs) on the nutritional regulation of IGF-I's actions, we compared the gene
      expression of IGF-I and the six IGFBPs in liver and kidney of protein-restricted
      (P5) and normally fed (P15) young rats. Using poly(A)+ Northern blot analysis, we
      observed a decrease in IGF-I messenger RNA (mRNA) at steady state in liver (-50%)
      and kidney (-60%). The increases in IGFBP-1 mRNA were parallel in these two
      tissues (liver, 5.7-fold; kidney, 4-fold). In contrast, the expression of the
      other IGFBP genes exhibited organ-specific regulation during protein restriction;
      although IGFBP-2 mRNA increased in liver in the P5 group (3-fold), it decreased
      slightly in kidney (-15%). IGFBP-3 mRNA declined by 30% in liver and was
      unchanged in kidney. IGFBP-4 mRNA increased by 50-88% in liver and was not
      modified in kidney. IGFBP-5 mRNA was not detected in liver and was identical in
      kidney of P15 and P5 rats. IGFBP-6 mRNA was not changed in either liver or kidney
      during protein restriction. To determine whether the changes in IGFBP mRNAs
      induced by protein restriction were associated with changes in the respective
      peptides, IGFBPs in supernatants of liver homogenates and in serum of the same
      rats were measured by ligand blot analyses. IGFBP-1 and IGFBP-2 Western
      immunoblot analyses were also performed in serum. By ligand blot, a 45,000 mol wt
      (M(r)) band (IGFBP-3) decreased in liver and serum of P5 rats, paralleling the
      changes in liver IGFBP-3 mRNA. A 30,000 M(r) band, consistent with IGFBP-1 and/or
      IGFBP-2, increased in liver. By immunoblot in serum, IGFBP-1 was only detectable
      in P5 rats, whereas IGFBP-2 decreased in the P5 group. By ligand blot, a 24,000
      M(r) band (IGFBP-4) declined slightly in serum (not detected in liver). Our study
      shows that protein restriction regulates the expression of four of six IGFBPs in
      rats, and this regulation is organ specific. The nutritional regulation of IGFBP
      peptides in biological fluids, in particular serum, seems to involve additional
      mechanisms.

PMID- 7518386
TI  - Evidence for two folding domains in glycoprotein hormone alpha-subunits.
AB  - We reconstituted ovine (o) LH alpha from its amino- and carboxyl-terminal
      fragments obtained as follows. oLH alpha was nicked at Arg46-Ser47 with Arg-C
      protease. Nicked oLH alpha disulfide bonds were broken by sulfitolysis, and its N
      terminal peptide and C-terminal glycopeptide were separated by Sephacryl S-200
      chromatography. Both fragments were mixed, reduced, and reoxidized. Reoxidation
      products were chromatographed on Sephacryl S-200, and an alpha-monomer fraction
      was recovered. The putative nicked alpha-monomer fraction was reassociated with
      native oLH beta, and the resulting oLH derivative was isolated by S-200
      chromatography with a reduced yield of 11% (intact subunits yield, 67% oLH). This
      preparation was 2.6% as active as oLH in a LH receptor binding assay. Two
      additional oLH derivatives were prepared. Cleavage at alpha Arg46-Ser47 alone,
      followed by reassociation with native oLH beta, produced Arg-C-nicked oLH
      alpha:oLH beta (14% yield) that was 3.3% as active as native oLH. Reduction
      reoxidation of Arg-C-nicked oLH alpha followed by reassociation with oLH beta
      produced reduced reoxidized-Arg-C-nicked oLH alpha:oLH beta (11% yield) that was
      1.8% as active as oLH. These results indicated that the nicked oLH alpha monomer
      had been reconstituted from its N- and C-terminal fragments.

PMID- 7518387
TI  - Galanin: a novel intraovarian regulatory peptide.
AB  - Galanin is a 29-amino acid peptide that acts as a neuropeptide in many tissues.
      To date, galanin action and the hormonal regulation of galanin gene expression
      have not been described in the ovary of any species. To study possible ovarian
      expression and regulation of galanin, immature gonadotropin-primed rats were
      given hCG (10 IU), and their ovaries were collected 0, 4, 8, 12, and 20 h after
      hCG treatment for determination of galanin messenger RNA (mRNA) concentration by
      solution hybridization. Galanin mRNA levels progressively increased after hCG
      administration, peaking at 12 h (2.4-fold increase vs. 0 h), with a subsequent
      return to 0 h levels at 20 h. To determine a possible ovarian role for galanin,
      rats were killed 48 h after gonadotropin administration, their ovaries were
      removed, and granulosa cells were harvested. These cells and the ovarian tissue
      remaining after granulosa cell collection (i.e. "shells") were each cultured for
      24 h with increasing concentrations of galanin (0, 10, 100, and 1000 nM) in the
      presence or absence of LH. The medium was examined for steroid production and
      metalloproteinase inhibitor activity. In granulosa cell cultures, galanin
      increased the levels of estradiol by 26% and had no effect on progesterone, but
      decreased metalloproteinase inhibitor activity by 61% in the conditioned medium.
      In the shell cultures, galanin increased estradiol, progesterone, and
      androstenedione in the medium, suggesting that galanin acts on cells other than
      granulosa cells or that galanin action requires a paracrine interaction between
      granulosa and thecal cells. Our data demonstrate that galanin message is
      increased by hCG, and that galanin acts to amplify ovarian steroidogenesis while
      decreasing metalloproteinase inhibitor activity. These findings establish that
      ovarian galanin mRNA is hormonally stimulated and that galanin acts as an
      intraovarian regulatory peptide.

PMID- 7518388
TI  - Coordinate actions of calcium and protein kinase-C in the expression of primary
      response genes in pituitary gonadotrophs.
AB  - Activation of GnRH receptors in cultured pituitary cells and alpha T3-1
      gonadotrophs caused prominent, but transient, increases in messenger RNAs for
      primary response genes (PRGs) including c-fos, c-jun, and junB. GnRH-induced
      stimulation peaked at 30 min and was dose related, with similar EC50 values
      (approximately 1 nM) for all three PRGs and higher maximum responses for junB
      than for c-jun and c-fos. The agonist-induced expression of PRGs was mimicked by
      activation of protein kinase-C with the phorbol ester phorbol 12-myristate 13
      acetate (PMA), which acted additively with GnRH at low concentrations of both
      stimuli. Depletion of cellular protein kinase-C by prior treatment with PMA
      reduced GnRH- and PMA-induced expression of PRGs. The protein kinase-C inhibitor
      staurosporine also attenuated agonist- and phorbol ester-induced PRG expression.
      Activation of Ca2+ entry by the calcium channel agonist BayK 8644 or high K(+)
      induced depolarization caused a concentration-dependent rise in intracellular
      Ca2+ ([Ca2+]i) and a concentration-dependent and transient expression of PRGs,
      albeit of smaller amplitudes than those elicited by GnRH and PMA. Ca(2+)
      dependent PRG expression was abolished by the calmodulin inhibitor W-7. Parallel
      measurements of [Ca2+]i and steady-state levels of PRG messenger RNAs indicated
      that intracellular Ca2+ exerted both additive and suppressive actions over its
      physiological concentration range on GnRH- and PMA-induced PRG expression. At
      lower intracellular calcium concentrations, calcium acted additively with low
      concentrations of GnRH and PMA. However, high calcium concentrations suppressed
      high agonist- and phorbol ester-induced PRG expression. In contrast, omission of
      Ca2+ from the extracellular medium significantly enhanced induction of PRGs.
      These findings indicate that GnRH-induced PRG expression in gonadotrophs is
      mediated by protein kinase-C and calcium, and that protein kinase-C-dependent
      induction of PRGs is modulated both positively and negatively by physiological
      changes in [Ca2+]i. Such coordinate actions of the two signaling molecules
      provide a mechanism for the control of PRG expression by preferential integration
      of low strength, and attenuation of high strength, extracellular signals.

PMID- 7518389
TI  - Characterization and relative abundance of alternatively spliced luteinizing
      hormone receptor messenger ribonucleic acid in the ovine ovary.
AB  - Complementary DNA (cDNA) clones encoding the LH receptor (LHR) were recently
      isolated from pig, rat, mouse, and human testes or ovaries. Many of the LHR cDNAs
      isolated from these species encoded incomplete and, therefore, possibly inactive
      forms of the LHR. The four major incomplete cDNAs, designated B, C, D, and E,
      were due to alternative splicing of the full-length cDNA, designated the A form.
      Northern analyses of messenger RNA (mRNA) encoding LHR in these species and in
      sheep revealed multiple mRNA species in ovarian tissue, but were unable to
      distinguish between the full-length (functional) form and the splice variants. We
      have used reverse transcription of mRNA, amplification via the polymerase chain
      reaction, and cDNA sequencing to determine which alternatively spliced mRNA
      species were present in ovine ovarian follicles and corpora lutea, and
      ribonuclease protection assays to confirm these results and determine the
      relative abundance of these splice variants. Ovine LHR cDNAs of the full-length A
      form, B form, and two novel splice forms, designated F and G, were isolated and
      sequenced. By using LHR cDNAs that spanned the regions of the gene in which the
      majority of splicing variation occurred, ribonuclease-protected fragments of
      different sizes were generated depending on which mRNA species (A-G) were
      present. It is estimated that the ratios of the steady state mRNA levels of the
      splice variant B form/full-length A form/G form/F form were 5-3.5:1:1:0.3. The E,
      C, and D forms were not detected, even when using the sensitive method of reverse
      transcription-polymerase chain reaction for the latter two forms. The overall
      level of expression of LHR mRNA was greater in corpora lutea than follicles, but
      the relative abundance of the splice variants was similar in follicles and
      corpora lutea.

PMID- 7518390
TI  - Mobile ionophores are a novel class of P-glycoprotein inhibitors. The effects of
      ionophores on 4'-O-tetrahydropyranyl-adriamycin incorporation in K562 drug
      resistant cells.
AB  - The decrease of the intracellular concentration of drug in resistant cells
      compared to sensitive cells is, in most cases, correlated with the presence, in
      the membrane of resistant cells, of a 170-kDa P-glycoprotein responsible for an
      active efflux of the drug. In an attempt to identify mechanism(s) by which
      multidrug resistance can be circumvented, we have examined the cellular
      accumulation of 4'-O-tetrahydropyranyl-adriamycin, alone and in conjunction with
      various ionophores on the one hand and with cyclosporin A on the other hand. The
      present study was performed using a spectrofluorometric method with which it is
      possible to follow continuously the uptake and release of fluorescent molecules
      by living cells, as the incubation of the cells with the drug proceeds.
      Erythroleukemia K562 cell lines were used. Using experimental conditions in which
      these ionophores were unable to modify either the intracellular pH, or the
      transmembrane potential, or to induce an intracellular ATP depletion, we have
      shown that mobile ionophores as well as cyclosporin inhibit the P-glycoprotein
      mediated efflux of 4'-O-tetrahydropyranyl-adriamycin in K562 resistant cells,
      whereas gramicidin, a channel-forming ionophore, does not. The concentration that
      must be used to inhibit 50% of the efflux was 0.7 microM for valinomycin, 0.4
      microM for nonactin, 0.2 microM for nigericin, 1.1 microM for monensin, 0.4
      microM for lasalocid, 1.2 microM for calcimycin and 0.4 microM for cyclosporin.
      Due to the high toxicity of the ionophores, the observation that they increased
      4'-O-tetrahydropyranyl-adriamycin accumulation in the multidrug-resistant cells
      is not correlated with an effect of these compounds on drug resistance. However,
      the correlation exists in the case of cyclosporin. From our data showing that
      lipophilic neutral complexes, formed between carboxylic ionophores and metal
      ions, are both able to inhibit the P-glycoprotein-mediated efflux of
      anthracycline we can infer that the lipophilicity but not the cationic charge is
      an important physical property.

PMID- 7518391
TI  - Kinetic measurement of the interaction between an oligosaccharide and lectins by
      a biosensor based on surface plasmon resonance.
AB  - Kinetic measurements of the interaction between an oligosaccharide and various
      lectins were performed using a biosensor based on surface plasmon resonance
      (SPR). A glycopeptide, prepared from asialofetuin and having a nearly homogeneous
      N-linked sugar chain, was immobilized on the surface of a sensor chip via the
      amino groups of its peptide moiety. The interactions of this bound glycopeptide
      with six lectins [Sambucus sieboldiana lectin, Maackia amurensis lectin, Aleuria
      aurantia lectin, Ricinus communis agglutinin-120 (RCA120), Datura stramonium
      lectin (DSA) and Phaseolus vulgaris leukoagglutinating lectin] were monitored in
      real-time with the change in the SPR response. Of these lectins, only RCA120 and
      DSA showed an increase in the SPR response, indicating that these two lectins
      bound specifically to the immobilized glycopeptide. The other lectins did not
      show any significant changes in the SPR response. These results are in good
      agreement with the binding specificity previously demonstrated with affinity
      chromatography. The association-rate constant (kass) and the dissociation-rate
      constant (kdiss) for the glycopeptide-RCA120 interaction were 3.4 x 10(5) M-1 s-1
      and 2.1 x 10(-3) s-1, respectively. The kass and kdiss determined for DSA were
      5.7 x 10(5) M-1 s-1 and 1.3 x 10(-3) s-1, respectively. Furthermore, the relative
      binding molar ratio to the glycopeptide was three times higher for RCA120 than
      for DSA, suggesting that this sugar chain possesses three binding sites for
      RCA120 and one for DSA. These parameters are expected to provide useful
      information for defining the interaction between oligosaccharides and lectins.

PMID- 7518392
TI  - Haematological improvement by long-term administration of recombinant human
      granulocyte-colony stimulating factor and recombinant human erythropoietin in a
      patient with severe aplastic anaemia.
AB  - A 6-year-old girl with post-hepatitic severe aplastic anaemia was referred to our
      hospital. Haematological examination showed a haemoglobin level of 5.2 g/dl,
      platelet count of 8,000/microliters, and white blood cell count of
      130/microliters with 17% neutrophils. She was treated with recombinant human
      granulocyte-colony stimulating factor (15 micrograms/kg/day i.v.) and cyclosporin
      A (6 mg/kg/day p.o.). The absolute neutrophil count gradually increased, but Hb
      and platelets were not improved. The intravenous administration of recombinant
      human erythropoietin (100 U/kg three times a week) was started, and the
      reticulocyte count reached 20,000/microliters on day 12. The platelets increased
      to 81,000/microliters after 16 months of combined administration of recombinant
      human granulocyte-colony stimulating factor, recombinant human erythropoietin and
      cyclosporin A. After 20 months of combined administration, the haematological
      results were: Hb, 13.1 g/dl; platelets 80,000/microliters; WBC, 9500/microliters
      with 40% neutrophils. After recombinant human granulocyte-colony stimulating
      factor treatment, the myeloid elements of the bone marrow and the number of
      granulocyte-macrophage colony forming units increased. Bone marrow erythropoiesis
      and erythroid colonies also increased after recombinant human erythropoietin
      administration. The clinical course suggested a beneficial effect of haemopoietic
      growth factors and cyclosporin A in post-hepatitic aplastic anaemia.

PMID- 7518393
TI  - The relationship of serum total sialic acid with serum acute phase proteins and
      lipoprotein (a) in patients with severe hypertriglyceridaemia.
AB  - Total serum sialic acid (TSA), recently shown to be a cardiovascular risk factor,
      was measured in 15 patients with severe hypertriglyceridaemia (fasting
      triglyceride > 2.3 mmol l-1) and 15 age and sex matched normal control subjects.
      To test the hypothesis that serum TSA is related in some way to serum acute phase
      proteins we also measured five acute phase proteins, namely alpha-1
      antichymotrypsin (ACT), alpha-1-acid-glycoprotein (AGP), alpha-2-macroglobulin
      (AMG), C-reactive protein (CRP) and haptoglobin (HAP) in both groups. Of note was
      the significantly elevated serum TSA in the severely hypertriglyceridaemic group
      as compared to normal subjects. Serum TSA being 71.9 +/- 11.7 mg dl-1 and 59.6 +/
      10.2 mg dl-1 respectively (P < 0.01 Mann-Whitney test). Serum CRP was
      significantly elevated in the type IV patients as compared to controls (6.4 +/-
      4.5 mg l-1 vs. 3.3 +/- 1.9 mg l-1 P < 0.05 Mann Whitney test) as was serum AMG
      (2.1 +/- 0.89 g l-1 vs. 1.5 +/- 0.53 g l-1 P < 0.05 Mann Whitney test). There was
      no correlation between serum TSA and lipoprotein (a) in either the normal or
      severely hypertriglyceridaemic subjects. We suggest that serum TSA could in part
      be related to hypertriglyceridaemia and serum acute phase proteins but that its
      property as a cardiovascular risk factor is not related to serum lipoprotein (a)
      concentrations.

PMID- 7518394
TI  - Neural-targeted gene therapy for rodent and primate hemiparkinsonism.
AB  - Expression of the rate-limiting enzyme for catecholamine biosynthesis, tyrosine
      hydroxylase (TH), via retroviral and plasmid expression vectors improved the
      efficacy of conditionally immortalized nigral neural cells in ameliorating rodent
      and nonhuman primate models of Parkinson's disease through neural
      transplantation. No improvement in rotational behavior occurred when sham
      transplants or nondopaminergic transplants were performed. Transplantation of the
      temperature-sensitive immortalized parental nigral neural line with a TH
      expression vector resulted in improvement for at least 2 months. Improvement was
      accompanied by HPLC evidence of increased L-DOPA production and
      immunocytochemical evidence of TH in the transfected cells increased over that of
      the parental line. No tumor formation was detected. These results suggest that:
      (1) temperature-sensitive immortalized neural cells may be genetically engineered
      successfully to improve their efficacy for the treatment of parkinsonism; and (2)
      a change in L-DOPA production, as opposed to growth factor production or other
      factors, is likely to account for the observed improvement, since the parental
      and derived lines differ by a single gene.

PMID- 7518395
TI  - S-adenosyl-L-homocysteine: a non-cytotoxic hypomethylating agent.
AB  - The cytotoxic effect caused by the hypomethylating agent S-adenosyl-L-
      homocysteine (SAH) was compared with that of two drugs commonly used to induce
      DNA hypomethylation, 5-azacytidine and 5-aza-2'-deoxycytidine. Two in vitro
      cytotoxicity tests, the tetrazolium MTT assay and the intracellular lactate
      dehydrogenase (LDH) activity test, suggest that SAH induces hypomethylation
      without causing any cytotoxic effect. We propose the use of SAH as a non
      cytotoxic agent which may be more suitable for inducing experimental DNA
      hypomethylation.

PMID- 7518397
TI  - Attenuation of agonist-induced desensitization of the rat substance P receptor by
      progressive truncation of the C-terminus.
AB  - We have investigated the C-terminal tail of the rat substance P receptor (SPR) as
      a domain essential for agonist-induced desensitization. Four progressively
      shorter mutants, using premature termination in the C-terminus, were constructed
      and compared with the unaltered SPR using ectopic expression of wild-type and
      mutant receptors in Xenopus oocytes. These mutants were designated D16, D47, D70
      and D96 with 16, 47, 70 and 96 amino acids residues deleted from the tail,
      respectively. Wild type SPR, D16 and D47 exhibited normal current responses when
      challenged with substance P, but D70 and D96 had reduced maximal current
      responses (70% and 5% of wild type SPR, respectively). D70, however, exhibited
      substantial resistance to substance P-induced desensitization in that 55%, versus
      8% for wild type SPR, of the peak current of the first response was preserved on
      second challenge with substance P. Therefore, a domain from residues 338 to 360
      of the rat SPR, though not necessary for the functional activity of the receptor,
      plays an essential role in agonist-induced desensitization.

PMID- 7518396
TI  - Activation of human peripheral monocytes by angiotensin II.
AB  - This study has investigated the ability of the vasoconstrictor peptide
      angiotensin II to activate human peripheral blood monocytes. Activation was
      monitored by measuring both the release of tumor necrosis factor alpha from
      monocytes and their adhesion to monolayers of human endothelial cells.
      Angiotensin II-elicited activation of monocytes was dose-dependent (half
      maximally effective concentration approximately 0.2 nM), saturable (maximally
      effective concentration approximately 5 nM), and sensitive to inhibition by the
      angiotensin type 1 receptor antagonist ZD 7155. Such direct actions imply that
      angiotensin II is an important candidate stimulus for the subendothelial
      infiltration of monocytes observed in atherogenesis and hypertension.

PMID- 7518398
TI  - Distinguishing between duplex and hairpin forms of RNA by 15N-1H heteronuclear
      NMR.
AB  - A general method is described for distinguishing RNA hairpins from RNA duplexes
      by application of two-dimensional filtered nuclear Overhauser enhancement spectra
      on a 1:1 mixture of unlabeled and 99% 15N-labeled molecules. The method is
      applied to the RNA dodecamer rGGCGCUUGCGUC which can form an intramolecular
      hairpin under low salt conditions and a duplex in high salt. This procedure
      allows unambiguous identification of RNA hairpins or duplexes under the same
      conditions that are used in the NMR solution structure determination.

PMID- 7518400
TI  - Injection of a K+ channel (Kv1.3) cRNA in fertilized eggs leads to functional
      expression in cultured myotomal muscle cells from Xenopus embryos.
AB  - The synthetic cRNA encoding for the major T lymphocyte K+ channel (Kv1.3) was
      injected into Xenopus fertilized eggs. Somites from embryos of stage 20-22 (about
      40 h post-fertilization at 19 degrees C) were dissociated and myotomal muscle
      cells were cultured in vitro for 2 days. The whole cell configuration of the
      tight seal patch-clamp technique was used to record K+ channel activity in
      cultured myocytes. These myocytes have two endogenous delayed-rectifiers
      (sustained and transient) and an inward-rectifier K+ currents, all of which are
      insensitive to the scorpion toxin charybdotoxin. Cultured myocytes dissociated
      from embryos injected with the Kv1.3 cRNA expressed the exogenous Kv1.3 channel.
      The Kv1.3 channel was identified by its physiological (a very low recovery from
      inactivation) and its pharmacological properties (a high sensitivity to
      charybdotoxin). This work demonstrates that Xenopus cultured myotomal muscle
      cells represent a very efficient and practical assay system for the functional
      expression of cloned ion channels.

PMID- 7518399
TI  - Formation of SRP-like particle induces a conformational change in E. coli 4.5S
      RNA.
AB  - E. coli P48 protein is homologous to the SRP54 component of the eukaryotic signal
      recognition particle. In vivo, P48 is associated with 4.5S RNA which shares a
      homology with eukaryotic SRP RNA. To study the interaction between P48 and 4.5S
      RNA in vitro, we used 4.5S RNA with fluorescein coupled to the 3'-terminal
      ribose. Upon binding of P48, the fluorescent 4.5S RNA shows a substantial
      decrease in fluorescence. Fluorescence quenching as well as anisotropy
      measurements reveal that the effect is not due to a direct interaction of P48
      with the dye. This suggests that the binding of P48 induces a conformational
      change in 4.5S RNA which affects the structure at the 3' end of the RNA. From
      equilibrium titrations with fluorescent 4.5S RNA, a dissociation constant of 0.15
      microns is obtained for the RNA.protein complex. The formation of the complex is
      not affected by GTP binding to or hydrolysis by P48.

PMID- 7518402
TI  - Expression of keratins in mouse vaginal epithelium.
AB  - In the epithelium of the rodent vagina proliferation and differentiation are
      tightly regulated by ovarian hormones. Estrogens stimulate proliferation and
      squamous differentiation, whereas progesterone redirects differentiation to a
      mucus-secreting epithelium formed by goblet-like cells. In the present study, we
      used monospecific keratin antibodies to show the expression and distribution of
      keratins in SENCAR mouse vaginal epithelium in different stages of the estral
      cycle and in ovariectomized animals. In ovariectomized animals, the vaginal
      epithelium expressed K6, K8, K13 and K14, but not K1. After estrogen treatment,
      K1 was expressed. During proestrus and estrus, the keratin pattern was
      essentially identical to that observed in 17 beta-estradiol-stimulated animals.
      In contrast, during the progestational stages (metaestrus and diestrus) or after
      progesterone treatment of ovariectomized mice, the most relevant change was the
      loss of K1. Together, these results show that K1 expression is induced by
      estrogens in the vaginal epithelium. In contrast, K6, K8, K13 and K14 are
      constitutively expressed even when squamous differentiation is not observed.

PMID- 7518401
TI  - Histotypic in vitro reorganization of dissociated cells from mouse fetal gonads.
AB  - Cell suspensions obtained from the testes of 13.5-14.5 day post coitum (dpc)
      mouse embryos reaggregate in cord-like structures following in vitro culture for
      24 h on a reconstituted basement membrane (Matrigel). Ovarian cells of the same
      fetal age or cell suspensions from sex indifferent gonadal ridges (11.5 dpc
      embryos) form an organized cell network but not cord-like structures. Antibodies
      directed against laminin or against the alpha 6 subunit of its integrin receptor
      prevent such morphogenetic processes. The addition of 5 micrograms/ml
      cycloheximide, cytochalasin B or tunicamycin also inhibits the phenomenon.
      Interestingly, compounds that increase intracellular cyclic AMP (cAMP) (dbcAMP,
      forskolin and isobutyl-1-methylxanthine) induce embryonic testicular cells to
      organize into structures similar to those assembled by ovarian or sex indifferent
      cell suspensions. These findings offer a simple in vitro model for studying some
      aspects of early gonad development and provide novel experimental evidence that
      cell motility and cell-cell adhesion, possibly regulated by cAMP dependent
      mechanisms, are likely to play an important role in gonad morphogenesis.

PMID- 7518403
TI  - The expression of liver-specific genes within rat embryonic hepatocytes is a
      discontinuous process.
AB  - The onset of transcription and mRNA accumulation of two liver-specific genes,
      carbamoylphosphate synthase (CPS) and phosphoenolpyruvate carboxykinase (PEPCK)
      in individual embryonic rat hepatocytes was investigated with in situ
      hybridization. In vitro CPS and PEPCK mRNAs can be induced prematurely in
      monolayer cultures of embryonic rat hepatocytes by glucocorticosteroids and
      cyclic AMP, i.e. the hormones that also regulate the expression of these genes in
      vivo. Upon exposure to hormones the cultures showed an interhepatocyte
      heterogeneity in CPS and PEPCK mRNA content. The pattern of accumulation of
      nuclear CPS mRNA-precursors indicates that this heterogeneity is generated by
      intercellular differences in the timing of the onset of transcription. However,
      under induced steady-state conditions the heterogeneity in the hepatocyte
      population persisted. The degree of heterogeneity is inversely related to the
      half life of the gene product (i.e. higher for PEPCK than for CPS and higher for
      mRNAs than for the respective proteins) and to the concentrations of inducing
      hormones. Accordingly, the interhepatocyte heterogeneity was most pronounced for
      the nuclear CPS mRNA-precursor. In contrast, no intercellular differences in the
      rate of degradation of the mRNAs were seen. These observations reveal that
      although all hepatocytes can and do express the genes, transcription of a gene in
      a particular cell is a discontinuous process.

PMID- 7518404
TI  - [A synthetic peptide-based immunoenzyme test system for the joint detection of
      human retrovirus (HTLV-1 and HIV-1) antibodies].
AB  - The study was made to develop an immunodiagnostic test system based on synthetic
      peptides able to detect in the same assay the total concentration of
      heterospecific antibodies against human retroviruses HTLV-1 and HIV-1. Three
      panels of reference-sera contained antibodies to HTLV-1 (70 specimens), HIV-1 (50
      and 16 specimens) and 4 synthetic peptides corresponding to protein fragments p19
      gag and gp46 env HTLV-1, gp120 and gp41 env HIV-1. Immune reactivity of the
      peptides with reference sera was measured in the immunoassay. It is established
      that relevant peptides mimic immunodominant B-epitopes of structural proteins
      HTLV-1 and HIV-1 and are recognized specifically by relevant antiviral
      antibodies. The enzyme immunoassay test system has been designed using a peptide
      combination in a single antigen complex. The system showed high diagnostic
      sensitivity.

PMID- 7518405
TI  - Fluorescein gonioangiography in diabetic neovascularisation.
AB  - Fluorescein angiography of the angle with the Goldmann gonioscopy lens was used
      to examine eyes of 100 Japanese patients with diabetes mellitus. Ocular tension
      was 21 mmHg or over in 31 of these 100 patients. Gonioscopy revealed angle
      neovascularisation in the eyes of 30 patients; however, fluorescein
      gonioangiography showed evidence of angle neovascularisation in 56 of the 100
      patients. Angle neovascularsation was first seen 20.3 +/- 4.1 s after injection
      of fluorescein dye. Of the newly formed vessels, the branching small vessels
      showed more prominent leakage than the larger vessels at the root. With
      progression of the retinopathy, angle neovascularisation became more severe.
      Following panretinal photocoagulation in 26 of the patients with neovascular
      glaucoma, angle neovascularisation remarkably regressed in 12 and moderately
      regressed in 7 patients. Ocular tension became normal in 13 patients. Two of 31
      patients with ocular hypertension were considered as cases of primary open-angle
      glaucoma as there was glaucomatous cupping, visual field defects and no evidence
      of newly formed vessels in the angle, as observed using fluorescein
      gonioangiography. Thus, fluorescein gonioangiography may be helpful in the
      diagnosis and clinical management of neovascular glaucoma.

PMID- 7518406
TI  - Effect of recombinant aprotinin on platelet activation in patients undergoing
      open heart surgery.
AB  - The hemostatic effect of recombinant (r)-aprotinin was studied in 41 patients
      undergoing cardiopulmonary bypass surgery. Flow cytometry was used to measure the
      expression of glycoprotein 1b (GP1b) and alpha-granule membrane protein 140 (GMP
      140) on platelets. Additional parameters studied were beta-thromboglobulin (beta
      TG), fibrinogen, fibrinopeptide A, plasminogen, platelet count, and the amount of
      postoperative chest tube drainage. Chest tube drainage was significantly less in
      the r-aprotinin-treated patients (p < 0.001). The percentage of platelets
      expressing GMP-140 increased to 9.7% in r-aprotinin patients and to 12.1% in
      controls during the surgery. The difference between both groups was not
      significant. Both values returned to baseline the next day. GP1b expression
      decreased in both groups by 33-38% during the surgery and returned to baseline
      the next day. GP1b expression and the plasma concentrations of fibrinogen,
      fibrinopeptide A, beta-TG, and plasminogen were not different in r-aprotinin and
      control patients. We conclude that r-aprotinin reduces blood loss during
      cardiopulmonary bypass surgery, but the primary mechanism is likely not through a
      protective effect on platelets.

PMID- 7518408
TI  - The polymorphism of the plasma inter-alpha-trypsin inhibitor (ITI) and its
      relationship to the heavy chain H1 subunit gene (ITIH1) at 3p211-212.
AB  - We investigated the ITI protein polymorphism in linkage analysis, using DraI and
      SstI as restriction fragment length polymorphism (RFLP) markers for the ITIH1
      gene. Isoelectric focusing (IEF) classification from 76 individual plasma samples
      and RFLP analysis from the corresponding DNA preparations disclosed linkage
      disequilibrium between the phenotypic IEF patterns of the two common ITI alleles,
      ITI*1 and ITI*2, and the diallelic DNA polymorphisms of two ITIH1 RFLPs,
      represented by DraI 4.0 kb and DraI 2.4 + 1.6 kb, and by SstI 6.7 kb and SstI 6.0
      + 0.7 kb, for the ITI 1 and ITI 2 IEF phenotypes, respectively, and by DraI
      4.0/2.4 + 1.6 kb and SstI 6.7/6.0 + 0.7 kb for the heterozygous ITI 1-2 IEF
      phenotype. Linked segregation between either of the RFLPs and the polymorphic ITI
      plasma protein locus has been established in nine informative family pedigrees.
      The less frequent allele in Europeans, ITI*3, is not represented by a further
      allelic restriction fragment in either RFLP. The significant linkage
      disequilibrium observed in this genetic study indicates that the ITI locus, with
      the alleles ITI*1 and ITI*2, must be close to, or reside within, the ITIH1 gene.
      The diallelic ITI protein polymorphism therefore provides an informative
      phenotypic marker system for chromosome 3p211-212.

PMID- 7518407
TI  - [Human CD34+ primitive hematopoietic progenitor cells: their role in the
      regeneration of the immunohematopoietic system].

PMID- 7518409
TI  - Unexpected inactivation of acceptor consensus splice sequence by a -3 C to T
      transition in intron 2 of the CFTR gene.
AB  - Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane
      conductance regulator gene (CFTR). Analysis of DNA from a pancreatic sufficient
      patient by means of denaturing gradient gel electrophoresis (DGGE) and subsequent
      DNA sequencing led to the identification of a novel potential splice mutation and
      a novel missense mutation in the CFTR gene. One C to T substitution (297-3C-->T)
      was found at the splice acceptor site of intron 2 and a T to C substitution at
      1213 was found in exon 7. To determine the effect of the potential splicing
      mutation on the patient's CFTR transcripts and by taking advantage of the
      "illegitimate" transcription phenomenon, RNA from EBV-lymphoblastoid cells was
      reverse transcribed and amplified by the polymerase chain reaction (PCR). Direct
      sequencing of the PCR product revealed that the transcript from the chromosome
      with the 297-3C-->T mutation exhibited the skipping of exon 3.

PMID- 7518410
TI  - Organization, expression, and chromosomal location of the mouse insulin-like
      growth factor binding protein 5 gene.
AB  - Insulin-like growth factor binding proteins (IGFBPs) constitute a family of at
      least six secreted proteins that bind insulin-like growth factors I and II (IGF-I
      and -II) and are capable of modifying IGF actions on target cells. We previously
      have purified an approximately 29-kDa IGFBP that is secreted by myoblasts during
      their terminal differentiation, have identified the protein as mouse IGFBP-5, and
      have cloned its cDNA (James et al., 1993). In this study, we have characterized
      the mouse IGFBP-5 gene, established its pattern of expression in the adult mouse,
      and defined its chromosomal location. The 17-kb gene was isolated on overlapping
      cosmid and lambda clones, and the four exons encoding the 5914-bp mRNA were
      sequenced. The 5' end of the gene was mapped by solution-hybridization
      ribonuclease protection assay to two discrete sites in exon 1 that were separated
      by 21 bp. The relative use of each transcription start site was found to vary
      among different mouse tissues. By interspecies backcross mapping using progeny
      derived from matings of [(C57BL/6J X Mus spretus)F1 x C57BL/6J] mice, the IGFBP-5
      gene was localized to the proximal region of chromosome 1 in tight linkage with
      fibronectin 1 (0 recombinants in 168 mice analyzed). Since this part of
      chromosome 1 shares homology with human chromosome 2q, and since fibronectin has
      been mapped to 2q34-q36, it is likely that human IGFBP-5 will reside on 2q as
      well. Characterization of the mouse IGFBP-5 gene now provides a starting point
      for studying the roles and regulation of this protein in development.

PMID- 7518412
TI  - Alternative splicing of the first nucleotide binding fold of CFTR in mouse testes
      is associated with specific stages of spermatogenesis.

PMID- 7518417
TI  - The potentiation of in vitro antibody response in low-responding mice by addition
      of cytokines.
AB  - The effect of exogenous cytokines on the antibody response to ARS-BGG after in
      vitro immunization in high- and low-responding strains of mice was determined.
      Twenty units/ml was established to be the optimal dose of cytokines. The low IgG
      antibody response to ARS-BGG in low-responding B10 mice was increased
      significantly by addition of either IL-4 or IFN-gamma. Similarly, the lower
      production of IgA antibodies was elevated by addition of either IL-2, IL-4, IL-5
      or IFN-gamma. The levels of IgM were not influenced by any of the cytokines
      tested. Cytokines, therefore, play a fundamental role in regulating the
      responsiveness to protein antigen.

PMID- 7518411
TI  - Linkage relationships between keratin-associated protein (KRTAP) genes and growth
      hormone in sheep.
AB  - The ovine hair keratin-associated protein (KRTAP) genes are grouped into several
      families. In this study, we analyzed linkage relationships between members of
      four KRTAP families and growth hormone and beta-hemoglobin. Restriction fragment
      length polymorphisms and a microsatellite polymorphism were typed in 10 sire
      groups from a flock of Australian Merino sheep. Two linkages, both previously
      undetected in sheep or any other mammal, were found. They were between growth
      hormone (GH) and the high-sulfur keratin gene family KRTAP1 (previously called
      high-sulfur B2C) at theta = 0.10, Z = 3.01 and between two high-glycine-tyrosine
      class genes, KRTAP6 (previously high-glycine-tyrosine type II) and KRTAP8
      (previously high-glycine-tyrosine type I-F), at theta = 0.15, Z = 5.0. The high
      level of conservation of the mammalian genome at these recombination values
      suggests that these linkages might be found in distantly related mammalian
      species.

PMID- 7518414
TI  - Positive and negative selection of antibody repertoires during B-cell
      differentiation.

PMID- 7518416
TI  - HIV-1 gp41 shares a common immunologic determinant with human T, B and monocyte
      cell lines.
AB  - Several examples of molecular mimicry between HIV-1 and human proteins are
      reported in the literature. Here we report on yet another example. The monoclonal
      antibody 3D6 recognized a 17-amino-acid region in HIV-1 gp41 (amino acids 602
      618) and could bind to the human T-cell lines H9 and Molt4, B cell lines Raji and
      Bjab, and monocyte cell lines U937 and HL60. By Western blot using 3D6, a strong
      band of 43 kDa and a very weak band of 80 kDa were detected in lysates of H9,
      Molt4, Raji and Bjab cell lines, but only a strong band of 43 kDa was observed in
      case of U937 and HL60 cells, under reducing or non-reducing conditions. The
      results indicate the presence of a common immunologic determinant between HIV-1
      gp41 and membrane proteins of these human T, B and monocyte cells.

PMID- 7518415
TI  - Distinctive developmental origins and specificities of murine CD5+ B cells.
AB  - CD5+ B cells constitute a small fraction of cells in the spleen of adult mice
      that exhibit numerous features serving to distinguish them from the bulk of
      IgD++CD5- "conventional" B cells. In this review we focus on two major questions
      relating to this population: 1) the relationship of CD5+ B cells to other B
      cells; and 2) the distinctive enrichment of particular autoreactive specificities
      in this subset. The nature of their origins is clarified by a thorough analysis
      of intermediate stages of early B-cell development in both fetal and adult
      tissues. The reactivity to bromelain-treated mouse red blood cells serves as a
      prototype system for the investigation of biased specificities in CD5+ B cells.
      These lines of investigation lead us to propose that CD5+ B cells in the adult
      are the remnant of a distinct fetal B-cell differentiation pathway wherein
      selection of cells from this fetal/neonatal population into the adult long-lived
      pool results in the over-expression of certain germline-encoded autoreactivities.

PMID- 7518413
TI  - How B-precursor cells are driven to cycle.

PMID- 7518420
TI  - Epstein-Barr virus-transformed human B lymphocytes produce natural antibodies to
      histones.
AB  - To study the mechanism(s) responsible for the appearance of Epstein-Barr virus
      (EBV)-induced anti-histone autoantibodies, peripheral blood B lymphocytes from
      healthy donors were infected with EBV and the resulting lymphoblastoid cell lines
      were tested for secretion of antibodies reacting with histones. It was found that
      EBV-transformed cells produce IgM antibody reactive with histones and that the
      frequency of EBV-inducible circulating B lymphocytes that produce antibodies to
      histones is at least 10(-5). Moreover, in cultures of tonsillar lymphoid cells,
      the enrichment in CD5+ B lymphocytes increases the percentage of EBV-transformed
      cultures making anti-histone IgM antibodies. EBV may therefore, also in vivo,
      induce natural anti-histone antibody by polyclonal B-cell activation without any
      requirement of antigen to trigger antibody response.

PMID- 7518419
TI  - Response to human acetylcholine receptor alpha 138-199: determinant spreading
      initiates autoimmunity to self-antigen in rabbits.
AB  - NZW rabbits immunised with a mixture of synthetic peptides representing alpha 138
      199 of the human acetylcholine receptor (AChR) alpha-subunit exhibited clinical,
      biochemical and electrophysiological signs of experimental autoimmune myasthenia
      gravis (EAMG), with raised levels of anti-rabbit AChR antibodies. Surprisingly,
      these were partly directed at the main immunogenic region (MIR, thought to be
      alpha 67-76) and alpha-Bungarotoxin binding sites on rabbit AChR, and reacted
      less well with human AChR. Moreover, they could be separated from the anti
      peptide antibodies by fractionation on immobilised peptide. We conclude that
      immunisation with these peptides led, by 'determinant spreading', to a response
      directed at self-AChR. Similar phenomena may have been overlooked in previous
      studies of responses to synthetic or recombinant AChR sequences. These findings
      suggest that autoimmunity could be induced by low-affinity, cross-reacting
      epitopes even when the observed serum response is highly specific for the
      autoantigen.

PMID- 7518418
TI  - A natural IgM antibody does inhibit polyclonal and antigen-specific IgM but not
      IgG B-cell responses.
AB  - Since a B-cell growth-inhibitory natural IgM antibody was identified in the
      culture supernatants of LPS-stimulated murine splenic B lymphocytes [11],
      attempts have been made to define other possible functional role(s) of this
      antibody. Here we show that this regulatory IgM is able to inhibit not only the
      proliferation of splenic B cells, but also their IgM secretion during LPS-induced
      polyclonal, as well as antigen (FITC-KLH)-specific antibody responses. In
      contrast, IgG1 production of hapten (FITC)-specific B cells neither during
      restimulation with LPS nor in the presence of carrier-specific T lymphocytes in
      vitro was affected by regulatory IgM. Therefore, whereas newly emerging naive B
      cells are highly susceptible, IgG-secreting B cells appear to be completely
      resistant to inactivation by the regulatory IgM autoantibody.

PMID- 7518423
TI  - Connective tissue protein in the prostate gland.
AB  - Clinically aggressive neoplastic development appears to be associated with
      extensive extracellular matrix biosynthesis. Collagen, non-collagenous protein
      and elastin from 21 specimens of benign hypertrophic prostate (BPH) and 15
      samples of cancerous prostate were determined. Collagen and non-collagenous
      protein concentrations of BPH were similar to those in prostatic carcinoma. The
      elastin concentration of well or moderately differentiated prostatic carcinoma
      was greater than that in BPH specimens. These results may provide an explanation
      as to the early antecedent or possible aetiology of prostatic carcinoma.

PMID- 7518422
TI  - Early health effects and biological monitoring in persons occupationally exposed
      to tetraethyl lead.
AB  - Dependent on the level of occupational exposure to tetraethyl lead, the
      occurrence of early signs of toxicity and the urinary excretion of triethyl lead,
      diethyl lead and total lead compounds were investigated. This was done in the
      following cohorts in the province of Hubei, China: 277 workers at gasoline depots
      exposed to gasoline, 36 traffic policemen exposed to automobile exhaust and 342
      public office workers (virtually non-exposed controls). Mean external tetraethyl
      lead exposure concentrations were 84.8 micrograms/m3 (as Pb) for the gasoline
      depot workers, 5.2 micrograms/m3 for traffic police and 1.1 microgram/m3 for the
      controls. No significant subclinical indications of organic lead toxicity were
      found in the group of traffic policemen compared with the controls. In the cohort
      of gasoline workers, however, there was a statistical increase (vs controls) in
      the frequency of appearance of tremor and of sinus bradycardia. When the cohort
      of gasoline workers was divided into subgroups of different ranges of exposure,
      dose-dependence was noted. In general, the urinary excretion of triethyl lead was
      very low compared to that of diethyl lead, which appears to be a sensitive and
      specific indicator of exposure to tetraethyl lead; total lead excretion did not
      correlate well with actual external tetraethyl lead exposure. On the basis of
      these data it seems that current occupational exposure limits for tetraethyl lead
      are inadequate and need to be revised. In addition, a biological limit, based on
      urinary diethyl lead excretion, may be proposed.

PMID- 7518425
TI  - [Surgical treatment of malignant tumors with mono- or multivisceral involvement].
AB  - Abdominal malignant tumors with a mono- or multivisceral involvement have a poor
      prognosis. Surgery is the only treatment with a hope to be curative. Between
      January 1989 and December 1992, 30 patients (12 men, 18 women, mean age 67.9)
      with abdominal malignancy involving one or more adjacent organs were operated on
      at the Department of Surgery, General Hospital, La Chaux-de-Fonds, Switzerland.
      The majority of the tumors originated from the colon and rectum. 64 organs were
      partially or totally resected. Every curative procedure consisted of an "en bloc"
      resection. 53% of the procedures were curative, 37% palliative and 10%
      explorative. Surgical morbidity reached 30% and hospital mortality 13% (one
      peroperative death). Surgery obtained a local control of the tumor in 75% of the
      cases. After curative procedures, local recurrence and secondary metastases
      appeared respectively in 25% and 19% of the cases. After a palliative operation,
      preoperative symptoms diminished or disappeared in 82% of the patients. Tumor
      curability essentially depends on invaded organs. Mobile organs can nearly always
      be excised. Non-mobile organs and retroperitoneum are resected much more
      difficultly. Surgical treatment of multiorgan malignancies is difficult. It
      involves a long and tenacious exploration before declaring the tumor non
      resectable.

PMID- 7518421
TI  - Assessment of location-specific human exposure to dichloro-diphenyl
      trichloroethane and benzenehexachloride in Gujarat state, India.
AB  - On the basis of the use of insecticides in agriculture and vector control
      programmes, two locations were selected in Gujarat state, India. In location 1
      the insecticides are used in both agriculture and vector control programmes while
      in location 2 they are used only in agriculture. Raw food commodities, water,
      soil and blood samples were collected from the people residing in these
      locations, and analysed for total dichloro-diphenyl trichloroethane and total
      benzenehexachloride residues. Residue levels were significantly lower in location
      2 than in location 1.

PMID- 7518424
TI  - Neonatal coxsackievirus group B infections: experience of a single department of
      neonatology.
AB  - Coxsackie infections in 14 infants born in a single neonatal unit were studied.
      The clinical presentation was mild nonspecific disease in eight infants and an
      overwhelming multiorgan disease in six. Three infants with systemic disease died.
      Vertical transmission of the virus from a colonized mother was documented in five
      mothers who infected seven infants. The remaining seven infants were infected
      horizontally, presumably from infected personnel. Coxsackie B1 was isolated in
      four of the cases and type B3 in two cases of systemic disease. Intravenous
      gammaglobulin combined with human leukocyte interferon was utilized in three
      cases of overwhelming disease and two infants of these infants survived.

PMID- 7518426
TI  - The N terminus of interleukin-8 (IL-8) receptor confers high affinity binding to
      human IL-8.
AB  - Interleukin-8 (IL-8) is a potent inflammatory mediator that belongs to the family
      of C-X-C chemokines. IL-8 promotes the activation and the extravasation of
      circulating neutrophils to the site of inflammation. Two IL-8 receptor isotypes
      (type A and B) are identified in human and rabbit neutrophils. IL-8 receptors
      belongs to the superfamily of G-protein-coupled receptors. Both receptor subtypes
      A and B bind with high affinity to human IL-8, but they exhibit distinct binding
      affinity to two functional and structurally related IL-8 peptides, melanoma
      growth-stimulating activity peptide (MGSA) and neutrophil-activating peptide-2
      (NAP-2). Human IL-8 receptor A binds with low affinity to MGSA or NAP-2. In
      contrast, human IL-8 receptor B binds MGSA with high affinity, and NAP-2 with
      lesser affinity. Using receptor subtype chimeras, we determined that the N
      terminal domain of the receptor confers ligand binding specificity (LaRosa, G.
      J., Thomas, K. M., Kaufmann, M. E., Mark, R., White, M., Taylor, L., Gray, G.,
      Witt, D., and Navarro, J. (1992) J. Biol. Chem. 267, 25402-25406). In this work,
      we characterized by molecular cloning and expression a mouse receptor
      structurally homologous to the IL-8 receptor. We isolated a clone by screening a
      mouse genomic library with a rabbit IL-8 receptor A cDNA fragment as a probe. The
      mouse clone exhibited an open reading frame encoding a 359-amino acid protein.
      Hydropathy plot analysis of the amino acid sequence reveals seven transmembrane
      domains characteristic of G-protein-coupled receptors. The N terminus and the
      second extracellular loop contain one and two putative N-glycosylation sites,
      respectively. The intracellular C-terminal tail contains Ser and Thr residues as
      potential phosphorylation sites. Northern blot analysis showed that the mouse
      receptor gene is expressed in mouse neutrophils. The mouse receptor shows 65, 74,
      66, and 70% amino acid identity to the rabbit IL-8 receptor subtypes A and B and
      human IL-8 receptor subtypes A and B, respectively. However, neither mouse
      neutrophils nor CHO cells expressing the mouse receptor bind human IL-8 in the
      nanomolar range. To identify the domain(s) conferring high affinity binding to IL
      8, we constructed rabbit/mouse receptor chimeras.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7518428
TI  - Disruption of integrin function and induction of tyrosine phosphorylation by the
      autonomously expressed beta 1 integrin cytoplasmic domain.
AB  - The cytoplasmic domains of integrin beta subunits are essential for the function
      of integrins in cell adhesion and signaling. A chimera combining the
      transmembrane and cytoplasmic domains of the beta 1 integrin subunit with an
      irrelevant extracellular domain derived from L3T4 (murine CD4) was tested for its
      ability to interfere with integrin function. Expression of this construct in
      cultured human embryonic kidney cells under the control of the inducible
      metallothionein promoter resulted in cell rounding and detachment, and blocked
      cell adhesion mediated by the beta 1 and alpha v beta 5 integrins. Expression of
      the beta 1 chimera at basal levels interfered with the tyrosine phosphorylation
      of a 125-kDa protein induced by antibody-induced clustering of integrins. Induced
      expression of the chimera resulted in sustained tyrosine phosphorylation of this
      protein, which could be enhanced by clustering of the chimera but was insensitive
      to clustering of integrins. These results demonstrate that the autonomously
      expressed beta 1 integrin cytoplasmic domain can act as a trans-dominant
      inhibitor of integrin function, presumably via competitive interactions with
      cytoplasmic components that are required for integrin-mediated cell adhesion and
      tyrosine phosphorylation.

PMID- 7518429
TI  - Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison
      with FGFR-1.
AB  - We have studied the signal transduction pathways of fibroblast growth factor
      receptor-4 (FGFR-4) and FGFR-1, which showed virtually identical acidic
      fibroblast growth factor binding profiles as well as tyrosine autophosphorylation
      upon activation in transfected L6 rat myoblasts and NIH3T3 mouse fibroblasts. A
      prominently tyrosyl-phosphorylated doublet of polypeptides of 85 kDa
      coprecipitated with activated FGFR-4 from both cell lines studied, but these
      polypeptides were not detected upon immunoprecipitation of activated FGFR-1.
      Furthermore, FGFR-4 induced only a weak tyrosyl phosphorylation of phospholipase
      C-gamma and no detectable tyrosyl phosphorylation of the SHC adaptor proteins in
      contrast to FGFR-1. No phosphorylation of Ras GTPase-activating protein, p64
      Syp/PTP1D tyrosine phosphatase, or association of the GRB2 adaptor protein SH2
      domain with these receptors was detected. Unlike FGFR-1, FGFR-4 induced only a
      barely detectable phosphorylation of the cellular serine/threonine kinase Raf-1
      and a weaker tyrosyl phosphorylation of mitogen-activated protein kinases than
      FGFR-1. Despite these differences, stimulation of both receptors resulted in
      increased DNA synthesis.

PMID- 7518430
TI  - Functional alterations in adult and fetal hemoglobin Sassari Asp-alpha 126(H9)-
      >His. The role of alpha 1 alpha 2 contact.
AB  - The effects of pH, organic phosphates (2,3-diphosphoglycerate), and temperature
      on the functional properties of both adult and fetal hemoglobin Sassari alpha
      (Asp-126-->His) have been studied. The functional properties of the adult variant
      are characterized by the following: (i) an oxygen affinity higher than that of
      normal HbA in all the experimental conditions used; (ii) a dramatic reduction of
      homotropic interactions (n50 very close to unity); and (iii) a significant
      decrease of the effect of 2,3-diphosphoglycerate, which is 35% lower than that
      observed on HbA. The fetal variant shows an increased oxygen affinity compared
      with normal HbF and an almost abolished heme-heme interaction. The molecular
      basis of these functional differences is discussed in terms of the possible role
      played by the substitution of alpha (Asp-26-->His) on the stability of the R
      state of the molecule due to a decreased interaction at the level of alpha 1
      alpha 2 contact.

PMID- 7518431
TI  - Glu192-->Gln substitution in thrombin yields an enzyme that is effectively
      inhibited by bovine pancreatic trypsin inhibitor and tissue factor pathway
      inhibitor.
AB  - Modeling studies have ascribed the remarkable resistance of thrombin to
      inhibition by the Kunitz type inhibitors, bovine pancreatic trypsin inhibitor
      (BPTI), and tissue factor pathway inhibitor (TFPI), to steric inhibition by the
      60-loop insertion, especially Trp60D (in the chymotrypsin numbering system).
      Indeed, deletion of Pro60B, Pro60C, and Trp60D from this loop (des-PPW) enhances
      BPTI inhibition (Ki = 16 nM) (Le Bonniec, B. F., Guinto, E. R., MacGillivray, R.
      T. A., Stone, S. R., and Esmon, C. T. (1993) J. Biol. Chem. 268, 19055-19061).
      Activated protein C, however, lacks an equivalent insertion loop but is
      nevertheless resistant to inhibition by these Kunitz inhibitors. A unique feature
      of thrombin and activated protein C is the presence of Glu at position 192.
      Substitution of Glu192 with Gln in activated protein C dramatically enhances
      inhibition by BPTI and TFPI (Rezaie, A. and Esmon, C. T. (1993) J. Biol. Chem.
      268, 19943-19948). We now demonstrate that thrombin E192Q (the Glu192-->Gln
      mutant) is inhibited by BPTI (Ki = 24 nM) or TFPI (Ki = 14 nM) much more
      effectively than wild type thrombin (Ki > 1 microM for both inhibitors). A
      thrombin mutant having both the des-PPW deletion and E192Q substitution binds
      BPTI (Ki = 35 pM) and TFPI (Ki = 25 pM) even tighter. BPTI can displace
      dansylarginine N-(-3-ethyl-1,5-pentanediyl)-amide from the active site of
      thrombin E192Q (Ki = 19 nM), indicating that BPTI interacts directly with the S1
      binding site in thrombin. The E192Q mutation and PPW deletion contribute
      comparably and additively to the binding energy of thrombin with the Kunitz
      inhibitors. We suggest that access to the active center of thrombin is less
      restricted than predicted from previous studies.

PMID- 7518432
TI  - Transcriptional regulation of alpha IIb integrin gene expression during
      megakaryocytic differentiation of K562 cells. Role of a silencer element.
AB  - A portion of the 5'-flanking region of the glycoprotein IIb (alpha IIb) integrin
      gene extending from -598 to +32 base pairs was isolated. This DNA segment is
      capable of driving low level base-line transcription in undifferentiated K562
      cells. It also contains elements which direct the markedly increased expression
      observed following megakaryocytic differentiation of K562 cells with phorbol
      dibutyrate. Analysis of hybrid alpha IIb-chloramphenicol acetyltransferase
      reporter gene constructs indicates that at least three regions within the -598 to
      +32 region control differentiation-dependent alpha IIb transcription. Two
      enhancer elements as well as a silencer domain all regulate chloramphenicol
      acetyltransferase transcriptional activity in K562 cells. Gel mobility shift
      experiments revealed that nuclear binding proteins are able to interact with all
      three DNA regions. A small region lying between -124 and -99 bases is able to
      bind to nuclear proteins in undifferentiated cells but not in differentiated
      cells as evidenced by gel mobility shift and foot-printing studies and
      corresponds to the silencer element identified in the functional studies.
      Therefore, the tissue-specific expression of alpha IIb may be controlled
      transcriptionally by both positive and negative factors with the silencer element
      playing a major role in regulating differentiation-dependent expression.

PMID- 7518433
TI  - Antagonist-dependent and -independent steps in the mechanism of adrenergic
      receptor internalization.
AB  - Epitope tagging and immunocytochemical techniques were used to examine the
      agonist-regulated internalization of human beta 2-adrenergic receptors in 293
      cells. In the absence of agonist, receptors tagged with monoclonal antibody
      remain in the plasma membrane for > 1 h. In the presence of agonist, tagged
      receptors are endocytosed within 10 min. Endocytosed receptors are located in
      endosomes and can be recycled to the plasma membrane. In the prolonged presence
      of agonist, receptor endocytosis continues even after maximum sequestration of
      surface receptors (measured by radioligand binding to intact cells) has occurred.
      The process of receptor endocytosis requires cellular ATP and is temperature
      dependent. At 4 degrees C, no agonist-induced redistribution of receptors located
      in the plasma membrane is observed. At 16 degrees C, agonist causes receptors to
      cluster in and around coated invaginations of the plasma membrane, but receptor
      endocytosis does not occur. Agonist treatment of cells at 16 degrees C, but not 4
      degrees C, predisposes receptors to agonist-independent endocytosis upon warming
      to 37 degrees C. These studies suggest that: 1) beta 2-adrenergic receptors
      reside stably in the plasma membrane of untreated cells, while they continuously
      cycle between the plasma membrane and endosomes in the presence of agonist; 2)
      agonist regulates an early step in the endocytosis mechanism, which is associated
      with the redistribution of adrenergic receptors between distinct microdomains of
      the plasma membrane; and 3) later steps in the endocytosis mechanism do not
      require agonist and may utilize the same endocytic machinery that mediates the
      endocytosis of constitutively recycling receptors.

PMID- 7518427
TI  - The relationship between low density lipoprotein-related protein/alpha 2
      macroglobulin (alpha 2M) receptors and the newly described alpha 2M signaling
      receptor.
AB  - alpha 2-Macroglobulin (alpha 2M)-methylamine binding to macrophages appears to
      involve two receptors. Binding of alpha 2M-methylamine to low density lipoprotein
      related protein (LRP) results in cellular uptake and degradation, while binding
      to a newly described alpha 2M signaling receptor elevates intracellular calcium
      ([Ca2+]i) and inositol phosphates. We now demonstrate that binding of
      lactoferrin, Pseudomonas exotoxin A, and lipoprotein lipase to LRP on macrophages
      results in increased [Ca2+]i and inositol 1,4,5-triphosphate. Receptor-associated
      protein, which binds to LRP but not the alpha 2M signaling receptor, blocks the
      lactoferrin signal but has no effect on alpha 2M-methylamine signaling. The
      latter observation supports our hypothesis that a distinct signaling receptor
      binds alpha 2M-methylamine. We further demonstrate that the signaling events
      induced by lactoferrin may involve a pertussis toxin-sensitive G protein, while
      the alpha 2M signaling receptor appears to be coupled to a pertussis toxin
      insensitive G protein.

PMID- 7518434
TI  - Potentiation of the oxidative burst of human neutrophils. A signaling role for L
      selectin.
AB  - Production of reactive oxygen intermediates (ROI) by the NADPH oxidase of
      neutrophils is a major mechanism of bacterial killing and, in pathologic
      circumstances, tissue damage. Integrins and selectins participate in neutrophil
      adhesion but may also play a role in intracellular signaling. The role of L
      selectin in ROI production and Ca2+ signaling in suspended neutrophils was
      examined using the DREG series of anti-L-selectin antibodies. NADPH oxidase
      activation was assessed in three ways: H2O2 production using either scopoletin or
      dihydrorhodamine and O2- production using cytochrome c. Alterations in [Ca2+]i
      were measured using Fura 2-AM and fluorescence spectrophotometry. Cross-linking
      of L-selectin with DREG and 2 degrees antibody did not trigger production of H2O2
      by itself but significantly enhanced the subsequent response to two soluble
      activating agents; the formyl peptide formyl-Met-Leu-Phe (fMLP) and tumor
      necrosis factor (TNF). Potentiation of the oxidative burst was observed using
      F(ab')2 fragments but not with irrelevant antibodies and was observed whether 2
      degrees antibody was added before or after fMLP. Cross-linking of L-selectin also
      triggered a rise in [Ca2+]i, due, in part, to release from intracellular stores.
      The intracellular Ca2+ chelator BAPTA blocked both the rise in [Ca2+]i and the
      potentiation of the oxidative burst in response to fMLP or TNF. We conclude that
      cross-linking of L-selectin induces intracellular signals, including release of
      Ca2+, which may contribute to potentiation of the oxidative burst.

PMID- 7518435
TI  - Expression and function of the low density lipoprotein receptor-related protein
      (LRP) in mammalian central neurons.
AB  - The low density lipoprotein receptor-related protein (LRP) is a multifunctional
      cell surface receptor, expressed in liver, that binds with high affinity and
      endocytoses several structurally and functionally distinct ligands, including
      apolipoprotein E-activated beta-migrating very low density lipoprotein, tissue
      type plasminogen activator, and alpha 2-macroglobulin. Here using in situ
      hybridization and quantitative RNase protection assays, we show that LRP is also
      expressed throughout the brain. LRP message is particularly high in the
      cerebellum, cortex, hippocampus, and brain stem. In addition, we demonstrate that
      a 39-kDa protein which copurifies with LRP and regulates the binding of other
      ligands to LRP is also expressed throughout the brain. Interestingly, expression
      of the 39-kDa message is approximately 100-fold of that found in liver,
      suggesting that the activity of LRP is more tightly regulated in brain tissue
      than in liver. Using primary cultures of isolated postnatal cortical neurons,
      [35S]methionine biosynthetic labeling and immunoprecipitation, we also
      demonstrate the de novo biosynthesis of LRP, the 39-kDa protein, as well as
      tissue-type plasminogen activator. Finally, using radioligand binding as well as
      fluorescent ligand binding and uptake studies, we show that LRP is functional in
      cortical neurons. These results taken together thus demonstrate expression of
      functional LRP in neuronal cells and suggest a potential role for LRP in brain
      protein and lipoprotein metabolism, development, and regeneration.

PMID- 7518436
TI  - Synthetic compound peptide simulating antigenicity of conformation-dependent
      autoepitope.
AB  - Proliferating cell nuclear antigen (PCNA), also known as auxiliary protein of DNA
      polymerase delta, is involved in DNA replication and repair. Certain patients
      with systemic lupus erythematosus (lupus) produce autoantibodies to PCNA and the
      autoantibody-defined epitopes of PCNA have been inferred to be conformation
      dependent. Based on antigenic properties of continuous primary structure
      peptides, compound peptides composed of covalently linked discontinuous sequences
      were synthesized and used as immunogens in rabbits. One compound peptide induced
      an antibody response to a nuclear antigen which demonstrated a cell cycle-related
      pattern of nuclear immunofluorescence with maximum expression in the DNA
      synthesis phase of the cell cycle associated with other features which simulated
      the conformation-dependent properties of lupus defined auto-epitopes. Other
      rabbit antibodies raised against different compound peptides did not show such
      properties and recognized epitopes which were continuous primary sequence
      regions. These results show that from analysis of antigenic sites on a protein,
      it might be possible to construct synthetic compound peptides which can mimic
      conformation-dependent epitopes recognized by spontaneously occurring
      autoantibodies.

PMID- 7518437
TI  - Mapping of cystic fibrosis transmembrane conductance regulator membrane topology
      by glycosylation site insertion.
AB  - Technical difficulties in obtaining three-dimensional structures of intrinsic
      membrane proteins continues to limit understanding of their function. However,
      considerable insight can be gained from their two-dimensional topological
      arrangement in the lipid bilayer. Efficient molecular genetic approaches are
      available to discern the topology of prokaryotic but not of eukaryotic membrane
      proteins. The absolute asymmetry of the sidedness of their N-glycosylation was
      employed here to develop such a method using the cystic fibrosis transmembrane
      conductance regulator (CFTR). Insertion by in vitro mutagenesis of N
      glycosylation consensus sequences (NXS/T) in predicted cytoplasmic and
      extracytoplasmic loops between hydrophobic sequences capable of traversing the
      membrane established the membrane topology of CFTR. This provides the first
      experimental evaluation of the original topological model of CFTR based solely on
      hydropathy algorithms and a method which may be generally applicable for the in
      vivo evaluation of the topology of other mammalian membrane proteins.

PMID- 7518440
TI  - Assembly of Na,K-ATPase alpha-subunit isoforms with Na,K-ATPase beta-subunit
      isoforms and H,K-ATPase beta-subunit.
AB  - cDNA encoding an epitope tag was joined to cDNAs encoding the chicken Na,K-ATPase
      beta 1 and beta 2 and H,K-ATPase beta-subunits to allow recognition of these beta
      subunits with the same monoclonal antibody during assembly assays. cDNAs encoding
      chicken Na,K-ATPase alpha 1, alpha 2, or alpha 3 and Na,K-ATPase beta 1 or beta 2
      or H,K-ATPase beta-subunits were transiently coexpressed in mammalian cells.
      Subunit assembly was assayed by immune precipitation of alpha-isoforms with a
      monoclonal antibody to the epitope-tagged beta-subunits. Each of the chicken
      alpha-isoforms assembled with each of the Na,K-ATPase beta-subunits and the H,K
      ATPase beta-subunit. Each of the epitope-tagged beta-subunits also assembled with
      a Na,K-ATPase/Ca-ATPase chimera that retained only 26 amino acids of the Na,K
      ATPase alpha-subunit, demonstrating that all three beta-subunits recognize this
      same alpha-subunit assembly site.

PMID- 7518441
TI  - Cyclic RGD peptide inhibits alpha 4 beta 1 interaction with connecting segment 1
      and vascular cell adhesion molecule.
AB  - The integrin supergene family includes receptors for a variety of extracellular
      matrix as well as cell surface proteins. Integrin alpha 4 has been shown to play
      an important role in leukocyte adhesion and extravasation during immune and
      inflammatory reactions. One recognition sequence known to interact with alpha 4
      is the Leu-Asp-Val (LDV) site contained in the connecting segment 1 region of
      fibronectin. Here we present evidence that shows that a conformationally
      restricted RGD-containing peptide is a potent inhibitor of cell adhesion mediated
      by alpha 4 beta 1, a receptor not convincingly documented to interact with RGD
      peptides. This peptide, 1-adamantaneacetyl-Cys-Gly-Arg-Gly-Asp-Ser-Pro-Cys
      (disulfide bridge between residues 1-8), blocks Jurkat cell adhesion to
      connecting segment 1-containing peptides as well as cell adhesion to cytokine
      activated endothelial cells. Adhesion of Jurkat cells to either vascular cell
      adhesion molecule-expressing cells or recombinant vascular cell adhesion molecule
      coated plates was likewise inhibited by this peptide. Furthermore, alpha 4 beta 1
      can bind directly to a cyclic RGD peptide immobilized to Sepharose. Integrins,
      alpha 5 beta 1, alpha v beta 3, alpha IIb/beta IIIa, alpha 2 beta 1, alpha v beta
      1, alpha v beta 5, alpha v beta 6, and alpha 3 beta 1, have been shown to
      recognize the Arg-Gly-Asp (RGD) sequence present in a variety of extracellular
      matrix proteins, and our data support the addition of alpha 4 beta 1 to this
      group. Further studies using molecular modeling of such cyclic RGD peptides could
      help in the design of more potent peptides or nonpeptide mimetics that could
      effectively block alpha 4-mediated activity and have potential application in a
      number of inflammatory diseases.

PMID- 7518439
TI  - Interaction of the c-fes proto-oncogene product with the interleukin-4 receptor.
AB  - Interleukin-4 (IL-4) regulates proliferation and differentiation of a variety of
      hematopoietic cell lineages through binding to the IL-4 receptor (IL-4R).
      Recently, we have demonstrated that IL-4 induces tyrosine phosphorylation of
      several proteins including the IL-4R and also induces association of
      phosphatidylinositol-3 kinase with the IL-4R. Since IL-4 induces tyrosine
      phosphorylation, we speculated that some tyrosine kinase may associate with the
      IL-4R. In this study, we demonstrate that IL-4 induces tyrosine phosphorylation
      of a protein closely related to, or identical to the c-fes protooncogene-encoded
      protein tyrosine kinase (FES). Furthermore, tyrosine phosphorylated FES or the
      closely related protein is found associated with the IL-4R. We also demonstrate
      that FES associates with the IL-4R in COS7 cells transfected with cDNA expression
      plasmids encoding these two proteins and in transfected COS7 cells IL-4 augments
      association of FES with the IL-4R and tyrosine phosphorylation of both FES and
      the IL-4R. Through a deletion analysis of the IL-4R we have identified a putative
      FES-binding site in the cytoplasmic domain of the IL-4R.

PMID- 7518442
TI  - The effects of phenylmethylsulfonyl fluoride on inositol-acylation and fatty acid
      remodeling in African trypanosomes.
AB  - Phenylmethylsulfonyl fluoride (PMSF) has been shown to inhibit the addition of
      ethanolamine phosphate to glycosylphosphatidylinositol (GPI) intermediates in
      Trypanosoma brucei (Masterson, W. J., and Ferguson, M. A. J. (1991) EMBO J. 10,
      2041-2045). Here we show that the Man3-GlcN-PI intermediate that accumulates in
      the presence of PMSF can undergo fatty acid remodeling, suggesting that the fatty
      acid remodeling enzymes are not specific for ethanolamine phosphate-containing
      GPI intermediates. We also show that PMSF inhibits the acylation of the inositol
      residue of GPI intermediates in bloodstream form T. brucei. Pulse-chase
      experiments demonstrate that glycolipid C (ethanolamine-PO4-Man3-GlcN-(acyl)PI)
      is not an obligatory precursor of glycolipid A (ethanolamine-PO4-Man3-GlcN-PI)
      and that glycolipid C can be converted to glycolipid A. These data suggest a
      model where glycolipid C is the terminal product of the GPI biosynthetic pathway,
      in dynamic equilibrium with glycolipid A. The inhibition of ethanolamine
      phosphate addition and inositol acylation by PMSF was also observed for procyclic
      forms of T. brucei but not for mammalian HeLa cells. These results suggest
      differences between the relevant parasite and mammalian enzymes.

PMID- 7518443
TI  - Receptor tyrosine phosphatase R-PTP-alpha is tyrosine-phosphorylated and
      associated with the adaptor protein Grb2.
AB  - Receptor tyrosine phosphatases (R-PTPases) have generated interest because of
      their suspected involvement in cellular signal transduction. The adaptor protein
      Grb2 has been implicated in coupling receptor tyrosine kinases to Ras. We report
      that a ubiquitous R-PTPase, R-PTP-alpha, is tyrosine-phosphorylated and
      associated in vivo with the Grb2 protein. This association can be reproduced in
      stably and transiently transfected cells, as well as in vitro using recombinant
      Grb2 protein. Association requires the presence of an intact SH2 domain in Grb2,
      as well as tyrosine phosphorylation of R-PTP-alpha. This observation links a
      receptor tyrosine phosphatase with a key component of a central cellular
      signalling pathway and provides a basis for addressing R-PTP-alpha function.

PMID- 7518438
TI  - Role of the amino-terminal residues of the interferon-induced protein kinase in
      its activation by double-stranded RNA and heparin.
AB  - We have previously reported that the amino-terminal residues 1-34 of the
      interferon-induced protein kinase (RNA-activated) (PKR) are necessary for its
      binding to and activation by double-stranded RNA (dsRNA) (Patel, R. C., and Sen,
      G. C. (1992) J. Biol. Chem. 267, 7671-7676). Here, we report that the amino
      terminal 24 residues are indispensable for these properties of the enzyme. The
      replacement of these residues with 14 unrelated residues fully restored the
      protein's dsRNA binding activity, but only partially restored the enzyme
      activity. Mutation of residues 18 and 19 revealed their importance in determining
      the affinity of PKR for dsRNA and its ability to phosphorylate eukaryotic
      initiation factor 2 alpha. These mutations, however, did not affect PKR's
      autophosphorylation activity. Deletion mutants that failed to bind to and be
      activated by dsRNA could be fully activated by the alternative activator,
      heparin. Thus, activation of PKR by dsRNA and heparin is mediated through
      different mechanisms that require different domains of the protein.

PMID- 7518444
TI  - Startle disease mutations reduce the agonist sensitivity of the human inhibitory
      glycine receptor.
AB  - The receptor for the inhibitory neurotransmitter glycine is a member of the
      ligand-gated ion channel receptor superfamily. Point mutations in the gene
      encoding the alpha 1 subunit of the glycine receptor-channel complex (GlyR) have
      recently been identified in pedigrees with the autosomal dominant neurological
      disorder, startle disease (hyperekplexia). These mutations result in the
      substitution of leucine or glutamine for arginine 271. This charged residue is
      located near the ion channel region and is predicted to affect chloride
      permeation through the GlyR. We found little evidence for this role from the
      anion/cation selectivity and lack of pronounced rectification of currents flowing
      through recombinant human alpha 1 subunit GlyRs containing the startle disease
      mutations. We reveal, however, that the startle disease mutations profoundly
      disrupt GlyR function by causing 230-410-fold decreases in the sensitivity of
      receptor currents activated by the agonist glycine. Additionally, we report
      corresponding 56- and 120-fold reductions in the apparent binding affinity (Ki)
      of glycine to the mutant GlyRs, but no change in the binding affinity of the
      competitive antagonist, strychnine. Thus, startle disease reduces the efficacy of
      glycinergic inhibitory neurotransmission by producing GlyRs with diminished
      agonist responsiveness. Our results show that startle disease mutations define a
      novel receptor activation site.

PMID- 7518445
TI  - Determinants of specificity of a baculovirus-expressed antibody Fab fragment that
      binds selectively to the activated form of integrin alpha IIb beta 3.
AB  - PAC1 is an IgM kappa murine monoclonal antibody that, like the Arg-Gly-Asp
      containing ligand fibrinogen, binds to integrin alpha IIb beta 3 only on
      activated platelets. The unique binding properties of PAC1 may be determined by
      its large size, its multivalency, and by variable region sequences, including an
      Arg-Tyr-Asp at residues 100A-C in H-CDR3. To study the molecular determinants of
      PAC1 function, baculoviruses containing cloned cDNA for the Fd heavy and kappa
      light chains of PAC1 were used to co-infect Sf9 insect cells. Infected cells
      secreted a soluble, monovalent, 50-kDa Fab fragment that bound saturably to
      agonist-stimulated platelets but not to resting cells. Fab binding was inhibited
      > 85% by 10 mM EDTA, 1 mM RGDS, 1 mM fibrinogen gamma 397-411, or 12 microM
      fibrinogen, but not by 1 mM RGES. Compared to PAC1 IgM, a 60-fold higher molar
      concentration of PAC1 Fab was required for half-maximal binding to platelets or
      for half-maximal inhibition of fibrinogen binding. PAC1 Fab bound to an activated
      form of alpha IIb beta 3 expressed in Chinese hamster ovary cells, but not to the
      resting form of the receptor in these cells or to alpha v beta 3 in human
      endothelial cells. Conversion of Asp100C to Glu by site-directed mutagenesis
      rendered the antibody inactive, indicating that the Arg-Tyr-Asp sequence in H
      CDR3 is essential for PAC1 recognition of alpha IIb beta 3. Binding of fibrinogen
      or PAC1 IgM to platelets induced tyrosine phosphorylation of a 140-kDa platelet
      protein, but binding of PAC1 Fab did not. These studies demonstrate that the
      specificity of PAC1 for activated alpha IIb beta 3 is determined by an integrin
      recognition sequence within H-CDR3. However, the strength of this binding
      interaction and the ability of PAC1 to trigger signaling in platelets also depend
      on antibody valency.

PMID- 7518446
TI  - Functional domains of human TIMP-1 (tissue inhibitor of metalloproteinases).
AB  - To define domains of tissue inhibitor of metalloproteinases (TIMP-1) that are
      important to its ability to inhibit fibroblast-type collagenase (FIB-CL), two
      different approaches were used: (i) competition with synthetic peptides modeled
      after the human TIMP-1 sequence and (ii) localization of epitopes of blocking
      antibodies. TIMP-1 consists of six loops, held in place by six disulfide bonds
      arranged in three knotlike structures. Several long peptides (n = 20-34),
      together covering three-fourths of the human TIMP-1 sequence, were able to block
      inhibition of human FIB-CL by TIMP-1. While most of these peptides were modeled
      after sequences in the NH2-terminal domain of the molecule (loops 1, 2, and 3),
      they also included two-thirds of the residues of the COOH-terminal domain
      including loops 4 and 5 and the COOH-terminal tail but not loop 6. Refinement by
      competition with shorter peptides (7-10 residues) showed that the region
      surrounding the second "disulfide knot" (Cys13-Cys124, Cys127-Cys174) plays a
      major role in the inhibition of FIB-CL. This region consists of two strands,
      residues 10-25 and 121-129, connected through Cys13-Cys124. Peptides from this
      region also directly inhibited FIB-CL in the absence of TIMP-1. Additional
      competing peptides included T2-11 of the NH2-terminal domain and T34-42, a highly
      conserved region in the middle of loop 1. Among a series of monoclonal and
      polyclonal antibodies (mAbs and pAbs) to TIMP-1, we identified two, one mAb and
      one pAb, that neutralized the activity of TIMP-1 against FIB-CL. Both recognized
      epitopes in loop 3. The epitope for the mAb was located in the sequence that
      marks the transition between loops 3 and 4, GCEEC127, a region also identified as
      important by peptide competition experiments. By contrast, the epitope for a
      nonblocking mAb was located in a short 9-residue segment of loop 4, and a
      nonblocking pAb recognized epitopes in loop 1, loop 6, and the COOH-terminal
      tail. Our findings suggest that the FIB-CL-TIMP-1 complex possesses multiple
      contact sites that involve several different subdomains of the inhibitor.

PMID- 7518447
TI  - Structural organization of the gene for human CD36 glycoprotein.
AB  - The cell-surface glycoprotein CD36 interacts with a large variety of ligands,
      including collagen types I and IV, thrombospondin, erythrocytes parasitized with
      Plasmodium falciparum, platelet-agglutinating protein p37, oxidized low density
      lipoprotein, and long-chain fatty acids. Its expression is restricted to
      platelets, monocytes, adipocytes, and some endothelial and epithelial cells and
      is regulated during cell activation, differentiation, and development. CD36
      belongs to a novel gene family of structurally related glycoproteins that
      includes CLA-1 and the lysosomal membrane glycoprotein LIMPII. To advance our
      knowledge on the genomic organization and the regulation of the cellular
      expression of the genes of this family, we have investigated the structural
      organization of the human CD36 gene and of its 5'-proximal flanking region. The
      CD36 gene is encoded by 15 exons that extend more than 32 kilobases on the human
      genome. Interestingly, the CD36 mRNA 5'-untranslated region is encoded by three
      exons. The 3'-untranslated region is contained in two exons, whose expression
      pattern can originate two mRNA forms. The cytoplasmic and transmembrane regions
      predicted at both terminal ends of the polypeptide chain are encoded by single
      exons, while the extracellular domain is encoded by 11 exons. The transcription
      initiation site of the CD36 gene is located 289 nucleotides upstream from the
      translational start codon. Sequence analysis of the proximal 5'-flanking region
      of the gene reveals the existence of a TATA box appropriately located with
      respect to the transcription initiation site and several potential cis-regulatory
      elements that might contribute to the transcriptional regulation of the CD36
      gene. Delineation of the structural organization of the CD36 gene may help in
      defining the boundaries of relevant structural and/or functional domains in CD36
      and, by extension, in the other members of the family.

PMID- 7518448
TI  - Functional and morphological abnormalities of mitochondria in human cells
      containing mitochondrial DNA with pathogenic point mutations in tRNA genes.
AB  - mtDNA with a point mutation in the tRNA(Ile) gene at nucleotide position 4269
      found in a patient with fatal cardiomyopathy and mtDNA with a point mutation in
      the tRNA(Arg) gene at 10410 found in a patient with Alpers disease were
      transferred cytoplasmically to rho zero HeLa cells (HeLa cells lacking mtDNA) to
      determine whether these novel mtDNA mutations in the tRNA genes are responsible
      for the defects in mitochondrial respiration function observed in these diseases.
      Cybrid clones (clones of rho zero HeLa cells with mtDNA from the patients) were
      isolated, and respiratory function and morphology of the mitochondria of the
      cybrid clones containing wild-type mtDNA and mutant mtDNA predominantly were
      compared. The results showed that accumulation of mutant mtDNA at 4269 alone
      without defects in the nuclear genome was sufficient to produce a disease
      phenotype, while mutant mtDNA at 10410 was not related to pathogenesis and
      reflected one of the rare polymorphic sites of human mtDNA. Moreover, we found
      that mitochondria in living cells were significantly swollen only when they
      contained predominantly the pathogenic mutant mtDNA, suggesting that the
      functional abnormality of mitochondria induced by pathogenic mtDNA mutations in
      tRNA genes is always associated with their swollen structure.

PMID- 7518449
TI  - Heterologous expression of human uteroglobin/polychlorinated biphenyl-binding
      protein. Determination of ligand binding parameters and mechanism of
      phospholipase A2 inhibition in vitro.
AB  - High level expression of a human polychlorinated biphenyl-binding protein (hPCB
      BP; also termed uteroglobin or CC10) was achieved in Escherichia coli. The
      recombinant protein (rhPCB-BP) constituted approximately 1% of total bacterial
      lysate proteins as judged from in vitro ligand binding assays using 4,4'
      bis([3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl. rhPCB-BP was purified to
      homogeneity in its native dimeric form. Saturation analysis experiments indicated
      a Kd of approximately 69 nM for the binding of 4,4'-bis([3H]methylsulfonyl)
      2,2',5,5'-tetrachlorobiphenyl to rhPCB-BP. The average number of binding sites
      (Bmax) calculated from such experiments on purified rhPCB-BP was 49 nmol/mg of
      protein and is close to the theoretical value of 1 mol of ligand associating with
      1 mol of dimeric protein. Purified rhPCB-BP was also found to cause a dose
      dependent inhibition of the enzyme porcine pancreatic phospholipase A2 (PLA2) in
      vitro. Increasing the concentrations of calcium abolished the inhibition of PLA2
      by rhPCB-BP, suggesting that the protein functions in vitro by sequestering Ca2+,
      an essential PLA2 cofactor. This notion was further supported by direct evidence
      that 45Ca2+ binds to rhPCB-BP. 1 mol of dimeric protein was also found to bind 2
      mol of ruthenium red, an organic dye that detects Ca(2+)-binding proteins, with a
      Kd of 3 microM. This binding was inhibited by Ca2+, with an IC50 of 7 mM.
      Finally, it was demonstrated that the addition of a high affinity ligand for the
      protein had no effect on its ability to inhibit PLA2 under conditions of limiting
      concentrations of calcium, and the addition of Ca2+ did not affect the binding
      characteristics of the PCB ligand, suggesting that these two properties of the
      protein are independent. Our results strongly support the notion that ligand
      binding is a conserved feature of the homologous uteroglobin/PCB-BP/cc10 proteins
      in different species, whereas our results question the suggested role of these
      proteins as specific inhibitors of PLA2.

PMID- 7518450
TI  - Triton X-100-resistant membrane complexes from cultured kidney epithelial cells
      contain the Src family protein tyrosine kinase p62yes.
AB  - We have previously isolated detergent-resistant membrane complexes from lysates
      of cultured kidney epithelial cells. These structures are enriched in proteins
      anchored by glycosylphosphatidylinositol, which are localized to the apical
      plasma membrane of epithelial cells, and have a distinctive lipid composition. We
      now report that the membranes contain p62yes, a non-receptor tyrosine kinase of
      the Src family. p62yes is the only major tyrosine-phosphorylated protein in the
      membrane complexes when they are isolated. Several proteins in the complexes can
      serve as substrates for phosphorylation by p62yes in vitro. The kinase is
      enriched at least 10-fold in the insoluble membranes compared to cellular
      membranes. p60c-src and p60v-src, which are highly homologous to p62yes, are not
      present in the complexes, even when the membranes are isolated from cells that
      overexpress the proteins. As p62yes is located near the apical plasma membrane of
      epithelial cells in several tissues in vivo, interaction of the kinase with other
      components of a detergent-resistant membrane microdomain may play an important
      role in transmembrane signal transduction.

PMID- 7518451
TI  - Identification of interleukin-2 receptor-associated tyrosine kinase p116 as novel
      leukocyte-specific Janus kinase.
AB  - Janus tyrosine kinase (JAK) has recently been linked to signal transduction by
      cytokine receptors of the hematopoietin family. We have recently described a 116
      kDa tyrosine kinase (p116) present in interleukin-2 (IL-2) receptor complexes in
      human YT cells that showed functional characteristics of a JAK kinase. These
      included receptor association, rapid and transient tyrosine phosphorylation
      kinetics in response to ligand, and in vitro autophosphorylating tyrosine kinase
      activity (Kirken, R. A., Rui, H., Evans, G. A., and Farrar, W. L. (1993) J. Biol.
      Chem. 268, 22765-22770). Here we extend these observations by demonstrating
      structural homologies between IL-2-modulated p116 and prolactin-modulated JAK2 in
      the rat T cell line Nb2. These include similar net charge as determined by
      nonequilibrium pH gradient electrofocusing and related primary structure based
      upon phosphopeptide mapping of V8 protease-digested hyperphosphorylated proteins.
      This putative JAK kinase underwent marked tyrosine phosphorylation in response to
      IL-2, IL-4, and IL-7, lymphoid growth factors that use the common IL-2 receptor
      gamma-chain, but not in response to prolactin. Furthermore, polyclonal antisera
      to JAK1, JAK2, or tyrosine kinase 2 did not recognize either rat or human p116.
      However, we identified the IL-2-modulated p116 as the recently cloned novel
      leukocyte Janus kinase, L-JAK, using an antiserum to a peptide corresponding to
      the COOH terminus of human L-JAK.

PMID- 7518452
TI  - cAMP and tumor necrosis factor competitively regulate transcriptional activation
      through and nuclear factor binding to the cAMP-responsive element/activating
      transcription factor element of the endothelial leukocyte adhesion molecule-1 (E
      selectin) promoter.
AB  - The cAMP-responsive element/activating transcription factor (CRE/ATF) element
      (also known as NF-ELAM1) of the endothelial leukocyte adhesion molecule-1 (ELAM
      1) promoter is necessary for full cytokine responsiveness. It differs from a
      consensus cAMP-responsive element (CRE) by 1 nucleotide (G-->A conversion) and
      does not mediate transcriptional activation in response to cAMP. We reported
      previously that cAMP actually decreases ELAM-1 synthesis induced by tumor
      necrosis factor (TNF). We now show that cAMP decreases the ELAM-1 promoter
      response to TNF in transient transfection assays in bovine aortic endothelial
      cells and that cAMP-mediated inhibition maps to the CRE/ATF element.
      Electrophoretic mobility shift assays using the ELAM-1 CRE/ATF DNA sequence
      reveal three complexes. Antibody supershift assays suggest the slowest migrating
      form (complex 1) contains ATF2, the middle form (complex 2) contains ATF2 and c
      Jun, and the fastest migrating form (complex 3) contains a CRE-binding protein.
      TNF increases c-Jun-containing complex 2 while diminishing complex 1, whereas
      cAMP decreases complex 2 and increases complex 1. Complex 3 is unchanged by
      either treatment, and the CRE-binding protein is not phosphorylated. Our data
      suggest that a change in the composition of the proteins binding to the CRE/ATF
      promoter element contributes to the competing effects of TNF and cAMP on ELAM-1
      gene expression.

PMID- 7518453
TI  - The use of DNA and RNA oligonucleotides in hybrid structures with longer
      polynucleotide chains to probe the structural requirements for moloney murine
      leukemia virus plus strand priming.
AB  - Plus strand priming during retroviral reverse transcription requires specific
      cleavage within the polypurine tract of the viral genome by the reverse
      transcriptase-associated RNase H. Previously it has been shown that a 190-base
      RNA-DNA hybrid containing the Moloney murine leukemia virus polypurine tract can
      serve as a substrate for the priming reaction. To investigate the structural
      requirements for the reaction, a series of DNA oligonucleotides was hybridized to
      the 190-base single-stranded RNA and tested as substrates for RNase H. At low
      enzyme concentrations, the sites of cleavage are located 17-23 nucleotides from
      the 3'-end of the DNA oligonucleotide, consistent with the observations of others
      that binding of the DNA polymerase at a primer terminus fixes the position of
      cleavage by RNase H. At higher enzyme concentrations, additional cleavages are
      observed in the RNA 3' of these sites, but there is no preference for cleavage at
      the plus strand origin. In contrast to the results with DNA oligonucleotides,
      hybridization of RNA oligonucleotides containing the polypurine tract to the 190
      base single-stranded DNA generates substrates that are cleaved at the origin and
      efficiently extended into DNA. An RNA oligonucleotide hybridized downstream of
      the polypurine tract is cleaved but not extended. These results support the view
      that RNase H cleavage to generate the plus strand primer is uncoupled from minus
      strand DNA synthesis.

PMID- 7518454
TI  - Mutagenesis of the conserved aspartic acid 443, glutamic acid 478, asparagine
      494, and aspartic acid 498 residues in the ribonuclease H domain of p66/p51 human
      immunodeficiency virus type I reverse transcriptase. Expression and biochemical
      analysis.
AB  - The effects of point mutations of the conserved Asp443, Glu478, Asn494, and
      Asp498 residues in the RNase H domain of human immunodeficiency virus type I (HIV
      1) reverse transcriptase (RT) have been analyzed. The mutants fell into two
      classes: (i) functional RT, but not detectable ribonuclease H activity, and (ii)
      uncharacterizable phenotype due to protein instability in the context of the
      RT/protease Escherichia coli co-expression system (Mizrahi, V., Lazarus, G. M.,
      Miles, L. M., Meyers, C. A., and Debouck, C. (1989) Arch. Biochem. Biophys. 273,
      347-358). The only mutation in the former class was D443A, whereas those in the
      latter included D443E, E478D, E478Q, D498E, D443A/D498N, D443E/D498N,
      D443Q/D498N, N494A, N494D, and N494Q. The results were interpreted in terms of
      the x-ray crystal structure of the HIV-1 RNase H domain (Davies, J. F., II,
      Hostomaska, Z., Hostomsky, Z., Jordan, S. R., and Matthews, D. A. (1991) Science
      252, 88-95) and a general acid-general base hydrolysis mechanism (Katayanagi, K.,
      Okumura, M., and Morikawa, K. (1993) Proteins Struct. Funct. Genet. 17, 337-346).
      The data suggested that structural perturbations within the RNase H domain
      interfered with maturation of the pol precursor by HIV-1 protease. Analysis of
      selected D443/D498 double mutants suggested that the destabilization caused by
      the D498N mutation could be suppressed by the formation of a new hydrogen bond
      between Asn498 and Asn443.

PMID- 7518456
TI  - Involvement of sialylated poly-N-acetyllactosaminyl sugar chains of band 3
      glycoprotein on senescent erythrocytes in anti-band 3 autoantibody binding.
AB  - When young and senescent erythrocytes, separated from freshly collected human
      blood, were incubated with 125I-goat anti-human IgG, binding of the IgG to the
      senescent cells was three times as high as that to the young cells. The release
      of the radioactivity from the anti-human IgG-bound senescent cells was enhanced
      by incubation with band 3 oligosaccharides but not by those digested with endo
      beta-galactosidase or neuraminidase. The senescent cells whose surface band 3
      saccharide chains were cleaved by endo-beta-galactosidase or totally removed by N
      glycosidase F showed decreased binding of the anti-human IgG. The radioactivity
      was effectively released from the anti-human IgG-bound senescent cells by
      digestion with endo-beta-galactosidase. The results suggest that senescent
      erythrocytes bind anti-band 3 autoantibody, and the antigenic sites on the cell
      surface are sialylated poly-N-acetyllactosaminyl sugar chains of band 3
      glycoprotein.

PMID- 7518455
TI  - Effects of pyrophosphate and nucleotide analogs suggest a role for ATP hydrolysis
      in cystic fibrosis transmembrane regulator channel gating.
AB  - Single channel analysis of artificial lipid planar bilayers reconstituted with
      wild-type human cystic fibrosis transmembrane regulator (CFTR) revealed a 10.3 pS
      Cl- selective channel that was activated upon phosphorylation with protein kinase
      A. Gating of this channel was described by a simple kinetic model consisting of a
      single open burst state and two closed states. The open probability of CFTR
      channels in bilayers increased as a function of increasing Mg-ATP concentration
      and exhibited negative cooperativity, suggesting the interaction of two or more
      ATP binding sites in channel gating. Mg-ATP increased channel open probability by
      decreasing the duration of the long-lived closed state but had no effect on
      either the mean open time or the fast closed state. ADP inhibited channel opening
      by precisely antagonizing the effect of ATP, suggesting that ADP inhibits the
      CFTR channel by competing with ATP for binding. Poorly hydrolyzable ATP analogs
      such as AMP-PNP and ATP gamma S, polyphosphates such as pyrophosphate (PPi) and
      tripolyphosphate (PPPi), and orthovanadate failed to support channel activity
      alone. When applied in the presence of ATP, these compounds all caused the CFTR
      channel to "lock" into a prolonged open burst state. These data support a model
      in which hydrolysis of ATP leads to closure of channels that have been opened by
      ATP.

PMID- 7518457
TI  - Identification of a novel type of alternative splicing of a tyrosine kinase
      receptor. Juxtamembrane deletion of the c-met protein kinase C serine
      phosphorylation regulatory site.
AB  - We have detected a novel type of structural variant of the tyrosine kinase
      receptor for c-met, also known as the hepatocyte growth factor receptor, in mouse
      tissues. The cDNA of the variant transcript of c-met lacks 141 base pairs, which
      predicts an in-frame deletion of 47 amino acids in the juxtamembrane region of
      the cytoplasmic domain. Sequence analysis of genomic DNA containing the c-met
      locus revealed that the absence of a discrete exon is responsible for this 141
      base pair deletion and that alternative splicing leads to production of two forms
      of transcript. These two forms of transcript are designated as c-metsm (for
      small) and c-metlg (for large) to distinguish the absence or presence of the 141
      base pair segment, respectively. The c-metsm variant is present in adult mouse
      tissues including kidney, liver, and brain as well as in 9-10-day-old embryos. In
      all cases, expression of c-metsm was lower than that of the normal transcript, c
      metlg. An antiserum against mouse c-Met protein immunoprecipitated corresponding
      protein forms of approximately 152 and approximately 145 kDa from whole kidney
      lysate under reducing conditions. The size difference of approximately 7 kDa
      between these isoforms corresponds to the predicted difference of 47 amino acids.
      The presence of this shorter variant transcript and its corresponding protein
      isoform in a variety of normal tissues suggests a physiological role. The deleted
      region in the cytoplasmic domain of c-metsm contains a sequence motif (S985ARS)
      for protein kinase C phosphorylation that has recently been shown to play a key
      role in the down-regulation of hepatocyte growth factor receptor kinase activity.
      The identification of this novel isoform, c-metsm, demonstrates that a tyrosine
      kinase receptor can achieve additional diversity by alternative splicing at a key
      regulatory site in its cytoplasmic domain.

PMID- 7518458
TI  - Bile acid efflux mediated by the rat liver canalicular bile acid transport/ecto
      ATPase protein requires serine 503 phosphorylation and is regulated by tyrosine
      488 phosphorylation.
AB  - Transfection of cDNA for a hepatocyte canalicular phosphoprotein, the rat liver
      canalicular bile acid transporter/ecto-ATPase/cell CAM 105, confers bile acid
      efflux and ecto-ATPase activities on heterologous cells (Sippel, C. J., Suchy, F.
      J., Ananthanarayanan, M., and Perlmutter D. H. (1993) J. Biol. Chem. 268, 2083
      2091). Our previous studies have also indicated that there is a positive
      correlation between the degree of phosphorylation of this transporter and its
      bile acid efflux activity. In this study, we introduced site-specific mutations
      of amino acid residues within a protein kinase C-dependent (T502A, S503A) and a
      tyrosine kinase-dependent (Y488F) phosphorylation consensus sequence in the
      cytoplasmic tail of this transporter in order to map the sites that are
      phosphorylated in vivo and to examine the functional significance of each. COS
      cells were transfected with mutant and wild type constructs using the pCDM8
      expression vector. Metabolic labeling and cell surface labeling showed that the
      mutant proteins were synthesized and delivered to the cell surface as efficiently
      as the wild type. Phosphoamino acid analysis using lysates of transfected cells
      showed that the T502A, S503A mutant contained [32P]phosphotyrosine, the Y488F
      mutant contained [32P]phosphoserine, and the wild type contained both 32P-labeled
      amino acids, proving that Ser503 and Tyr488 are the only amino acids
      phosphorylated in this system under control conditions. Bile acid transport
      activity was completely abrogated in cells transfected with the T502A, S503A
      mutant cDNA and was retained but altered in kinetic characteristics in cells
      transfected with the Y488F mutant cDNA, even though both of these constructs
      conferred ecto-ATPase activity to the same extent as the wild type cDNA. Taken
      together, these data show that the bile acid efflux activity of this transporter
      requires site-specific phosphorylation of Ser503 and is regulated by site
      specific phosphorylation of Tyr488.

PMID- 7518459
TI  - Close similarity of baculovirus-expressed n-chimaerin and protein kinase C alpha
      as phorbol ester receptors.
AB  - n-Chimaerin is a recently described phorbol ester receptor that shares homology
      in its N-terminal region with the cysteine-rich zinc finger domain of protein
      kinase C. We have expressed n-chimaerin in insect cells using the baculovirus
      system and have used the isolated, recombinant n-chimaerin to characterize
      phorbol ester binding and structure-activity relations, lipid requirements, and
      inhibitor sensitivity. We find that n-chimaerin expressed in the baculovirus
      system bound [3H]phorbol 12,13-dibutyrate with high affinity (0.17 +/- 0.01 nM).
      Although having only a single cysteine-rich zinc finger region compared to two
      for protein kinase C, n-chimaerin thus closely resembled protein kinase C alpha.
      n-Chimaerin was likewise virtually indistinguishable from protein kinase C alpha
      in phorbol ester structure-activity relations, in phospholipid requirements, and
      in inhibition of binding by sphingosine and calphostin C, protein kinase C
      inhibitors acting on the regulatory domain. We conclude that a number of typical
      approaches used to implicate protein kinase C in biological function in cells do
      not discriminate between the n-chimaerin and protein kinase C classes of phorbol
      ester receptors.

PMID- 7518460
TI  - Phosphorylation and identification of a major tyrosine phosphorylation site in
      protein tyrosine phosphatase 1C.
AB  - Protein tyrosine phosphatase 1C (PTP1C) was the first member of the protein
      tyrosine phosphatase family demonstrated to contain the src homology 2 (SH2)
      domain. This enzyme is believed to play a role in regulating downstream signaling
      in hematopoietic cells since it was predominantly expressed in these cells.
      However, recent studies have revealed that the protein is expressed in other
      tissues as well. This report describes both the phosphorylation of PTP1C in non
      hematopoietic cells treated with growth factors (in vivo) and incubation of
      purified PTP1C with a variety of protein kinases (in vitro). PTP1C was
      transiently phosphorylated in A431 and 293 cells and also when the purified
      enzyme was incubated with receptor protein tyrosine kinases. In vitro, the
      tyrosine-phosphorylated PTP1C underwent rapid auto-dephosphorylation, an effect
      which could be blocked by the addition of sodium vanadate. On the other hand,
      cells containing a PTP1C in which the catalytic site had been inactivated through
      mutagenesis, stably phosphorylated the phosphatase. These results suggested that
      PTP1C was responsible for its own auto-dephosphorylation. The sites of tyrosine
      phosphorylation were characterized from purified enzyme following treatment with
      insulin receptor kinase and from PTP1C expressed in 293 cells which had been
      stimulated with platelet-derived growth factor. Through the techniques of peptide
      mapping and microsequencing, Tyr538 was determined to be the major
      phosphorylation site. This result was confirmed in vivo through site-specific
      mutagenesis of PTP1C expressed in 293 cells; changing Tyr538 to Phe538 completely
      abolished tyrosine phosphorylation of the molecule. In addition, Tyr538 lies
      within the sequence ESEYGNI which can be correlated with the consensus sequence
      pYXNX associated with GRB2 binding. These results suggest that PTP1C plays a
      prominent role in growth factor receptor-mediated signal transduction within both
      hematopoietic cells and tissues of non-lymphoid origin.

PMID- 7518461
TI  - Regulation of calcineurin phosphatase activity and interaction with the FK-506.FK
      506 binding protein complex.
AB  - The immunosuppressant FK-506 (tacrolimus) forms a complex with a ubiquitous
      intracellular receptor, FK-506 binding protein (FKBP12), and this complex
      inhibits the heterodimeric Ca2+/calmodulin-dependent phosphatase, calcineurin, an
      essential component of the T-cell receptor signal transduction pathway. Using a
      series of truncated calcineurin catalytic subunits, we show here that a region
      within the catalytic subunit that regulates phosphatase activity, the
      autoinhibitory domain, also regulates the Ca(2+)-dependent interaction of
      calcineurin with the FK-506.FKBP12 complex. Deletion of this domain produces
      constitutive activation of the phosphatase as demonstrated by transient
      transfection experiments in which expression of the truncated protein permitted
      Ca(2+)-independent induction of interleukin-2 transcription. Thus, deletion of
      the autoinhibitory domain is necessary and sufficient to constitutively activate
      calcineurin (CaN). Furthermore, CaN A467-492, an inhibitory peptide based on the
      autoinhibitory domain from calcineurin (ITSFEEAKGLDRINERMPPRRDAMP), inhibited
      dephosphorylation of the RII peptide substrate competitively with a Ki = 4
      microM, consistent with binding of the autoinhibitory domain at the active site
      of the enzyme. To assess the role of the autoinhibitory domain in regulating the
      interaction of CaN with the FK-506.FKBP12 complex, we reconstituted wild type and
      mutant phosphatase heterodimers using in vitro transcribed and translated
      subunits. Association of the reconstituted calcineurin heterodimers with FKBP12
      was dependent on FK-506. In the case of the wild type heterodimer, association
      with the FK-506.FKBP12 complex was also dependent upon Ca2+; however, mutant
      catalytic subunits, in which the autoinhibitory domains were deleted, associated
      with the drug-binding protein complex in the presence of 10 mM EGTA. These
      results indicate that the conserved autoinhibitory domain regulates both Ca(2+)
      dependent phosphatase activity and association with the FK-506.FKBP12 complex.

PMID- 7518462
TI  - Substrate-specific binding of the amino terminus of fibronectin to an integrin
      complex in focal adhesions.
AB  - The assembly of fibronectin fibrils involves the amino-terminal and cell adhesion
      domains of fibronectin as well as alpha 5 beta 1 integrins. Efficient binding of
      biotinylated or radioiodinated 70-kDa amino-terminal fragments occurred only if
      fibroblasts were plated on fibronectin or on 180- or 85-kDa cell adhesion
      fragments of fibronectin. On an 11.5-kDa fragment of fibronectin that included
      the Arg-Gly-Asp (RGD) sequence, but not the synergy site, binding was reduced 50
      fold. Conformation of the 180-kDa fragment was important for direct binding
      interactions with the amino terminus of fibronectin. No binding was seen if cells
      were plated on type I collagen, vitronectin, RGD peptides or antibodies to alpha
      5 beta 1 integrins. High affinity interactions between invasin and alpha 5 beta 1
      integrin promoted low levels of binding. Monoclonal antibodies that blocked the
      function of either the RGD or the synergy site inhibited binding of 125I-labeled
      70-kDa fragments to cells by approximately 60%. By fluorescence and interference
      reflection microscopy, biotinylated 70-kDa fragments were shown to co-localize
      with alpha 5 beta 1 integrins in focal adhesions. We propose that cell-mediated
      binding of the amino terminus of fibronectin involves interactions with both
      fibronectin and its alpha 5 beta 1 integrin receptor in an activated complex.

PMID- 7518463
TI  - Cysteine3 of Src family protein tyrosine kinase determines palmitoylation and
      localization in caveolae.
AB  - Recent work has demonstrated that p56lck, a member of the Src family of protein
      tyrosine kinases (PTKs), is modified by palmitoylation of a cysteine residue(s)
      within the first 10 amino acids of the protein (in addition to amino-terminal
      myristoylation that is a common modification of the Src family of PTKs). This is
      now extended to three other members of this family by showing incorporation of
      [3H]palmitate into p59fyn, p55fgr, and p56hck, but not into p60src. The
      [3H]palmitate was released by treatment with neutral hydroxylamine, indicating a
      thioester linkage to the protein. Individual replacement of the two cysteine
      residues within the first 10 amino acids of p59fyn and p56lck with serine
      indicated that Cys3 was the major determinant of palmitoylation, as well as
      association of the PTK with glycosyl-phosphatidylinositol-anchored proteins.
      Introduction of Cys3 into p60src led to its palmitoylation. p59fyn but not p60src
      partitioned into Triton-insoluble complexes that contain caveolae,
      microinvaginations of the plasma membrane. Mapping of the requirement for
      partitioning into caveolae demonstrated that the amino-terminal sequence Met-Gly
      Cys is both necessary and sufficient within the context of a Src family PTK to
      confer localization into caveolae. Palmitoylation of this motif in p59fyn also
      modestly increased its overall avidity for membranes. These results highlight the
      role of the amino-terminal motif Met-Gly-Cys in determining the structure and
      properties of members of the Src family of PTKs.

PMID- 7518465
TI  - Ultrastructural analysis of the dynactin complex: an actin-related protein is a
      component of a filament that resembles F-actin.
AB  - The dynactin complex visualized by deepetch electron microscopy appears as a
      short filament 37-nm in length, which resembles F-actin, plus a thinner,
      laterally oriented filament that terminates in two globular heads. The locations
      of several of the constituent polypeptides were identified on this structure by
      applying antibodies to decorate the dynactin complex before processing for
      electron microscopy. Antibodies to the actin-related protein Arp1 (previously
      referred to as actin-RPV), bound at various sites along the filament,
      demonstrating that this protein assembles in a polymer similar to conventional
      actin. Antibodies to the barbed-end actin-binding protein, capping protein, bound
      to one end of the filament. Thus, an actin-binding protein that binds
      conventional actin may also bind to Arp1 to regulate its polymerization.
      Antibodies to the 62-kD component of the dynactin complex also bound to one end
      of the filament. An antibody that binds the COOH-terminal region of the 160/150
      kD dynactin polypeptides bound to the globular domains at the end of the thin
      lateral filament, suggesting that the dynactin polypeptide comprises at least
      part of the sidearm structure.

PMID- 7518464
TI  - ERM family members as molecular linkers between the cell surface glycoprotein
      CD44 and actin-based cytoskeletons.
AB  - The ERM family members, ezrin, radixin, and moesin, localizing just beneath the
      plasma membranes, are thought to be involved in the actin filament/plasma
      membrane association. To identify the integral membrane protein directly
      associated with ERM family members, we performed immunoprecipitation studies
      using antimoesin mAb and cultured baby hamster kidney (BHK) cells metabolically
      labeled with [35S]methionine or surface-labeled with biotin. The results
      indicated that moesin is directly associated with a 140-kD integral membrane
      protein. Using BHK cells as antigens, we obtained a mAb that recognized the 140
      kD membrane protein. We next cloned a cDNA encoding the 140-kD membrane protein
      and identified it as CD44, a broadly distributed cell surface glycoprotein.
      Immunoprecipitation with various anti-CD44 mAbs showed that ezrin and radixin, as
      well as moesin, are associated with CD44, not only in BHK cells, but also in
      mouse L fibroblasts. Furthermore, immunofluorescence microscopy revealed that in
      both BHK and L cells, the Triton X-100-insoluble CD44 is precisely colocalized
      with ERM family members. We concluded that ERM family members work as molecular
      linkers between the cytoplasmic domain of CD44 and actin-based cytoskeletons.

PMID- 7518466
TI  - Differential organization of desmin and vimentin in muscle is due to differences
      in their head domains.
AB  - In most myogenic systems, synthesis of the intermediate filament (IF) protein
      vimentin precedes the synthesis of the muscle-specific IF protein desmin. In the
      dorsal myotome of the Xenopus embryo, however, there is no preexisting vimentin
      filament system and desmin's initial organization is quite different from that
      seen in vimentin-containing myocytes (Cary and Klymkowsky, 1994. Differentiation.
      In press.). To determine whether the organization of IFs in the Xenopus myotome
      reflects features unique to Xenopus or is due to specific properties of desmin,
      we used the injection of plasmid DNA to drive the synthesis of vimentin or desmin
      in myotomal cells. At low levels of accumulation, exogenous vimentin and desmin
      both enter into the endogenous desmin system of the myotomal cell. At higher
      levels exogenous vimentin forms longitudinal IF systems similar to those seen in
      vimentin-expressing myogenic systems and massive IF bundles. Exogenous desmin, on
      the other hand, formed a reticular IF meshwork and non-filamentous aggregates. In
      embryonic epithelial cells, both vimentin and desmin formed extended IF networks.
      Vimentin and desmin differ most dramatically in their NH2-terminal "head"
      regions. To determine whether the head region was responsible for the differences
      in the behavior of these two proteins, we constructed plasmids encoding chimeric
      proteins in which the head of one was attached to the body of the other. In
      muscle, the vimentin head-desmin body (VDD) polypeptide formed longitudinal IFs
      and massive IF bundles like vimentin. The desmin head-vimentin body (DVV)
      polypeptide, on the other hand, formed IF meshworks and non-filamentous
      structures like desmin. In embryonic epithelial cells DVV formed a discrete
      filament network while VDD did not. Based on the behavior of these chimeric
      proteins, we conclude that the head domains of vimentin and desmin are
      structurally distinct and not interchangeable, and that the head domain of desmin
      is largely responsible for desmin's muscle-specific behaviors.

PMID- 7518471
TI  - Generation and characterization of a mouse/human chimeric antibody directed
      against extracellular matrix protein tenascin.
AB  - The murine anti-tenascin monoclonal antibody 81C6, following iodination, has been
      shown to be an efficient localizing and therapeutic agent in both subcutaneous
      and intracranial human glioma xenograft models in athymic mice and rats.
      Similarly, effective monoclonal antibody 81C6 localization has been demonstrated
      in glioma patients, and Phase I trials with the intact murine IgG2b kappa
      molecule are currently in progress. In order to maximize the potential for
      repeated administration by minimizing murine Fc-mediated immunogenicity and
      reducing Fc-mediated immune effects, we created murine 81C6 variable region/human
      IgG2 chimeric monoclonal antibodies by the molecular cloning of the variable
      region genes of mouse 81C6 and their genetic linkage to human constant region
      exons. The resulting chimeric constructs were introduced into SP2/0 cells, and
      stable transfectomas were selected by G418 and mycophenolic acid resistance. The
      resistant clones were screened for anti-tenascin activity on tenascin-coated
      plates by enzyme-linked immunosorbent assay. The N-terminal amino acid sequence
      of both heavy and light chains of the purified chimeric 81C6 antibody matched
      exactly with that of the native mouse 81C6 as well as with that deduced from the
      nucleotide sequence. The production level of chimeric 81C6 (13.9 mg/ml) from
      ascites in the highest expressing transfectoma was much higher than that of
      native mouse 81C6 (2.5 mg/ml). The chimeric antibody showed the same specificity
      and equivalent affinity for human intact tenascin or tenascin-expressing cells as
      the native mouse 81C6 antibody. Direct comparison of radioiodinated chimeric and
      radioiodinated mouse 81C6 biodistribution in subcutaneous and intracranial
      xenograft-bearing mice showed higher tumor-to-normal tissue ratios for chimeric
      81C6 as compared with native mouse 81C6. The improved localizing and clearance
      characteristics of chimeric 81C6 in xenograft model systems suggests that
      chimeric 81C6 would be an improved reagent for intracompartmental therapy of
      tenascin-expressing tumors in the human central nervous system.

PMID- 7518468
TI  - Involvement of the "I" domain of LFA-1 in selective binding to ligands ICAM-1 and
      ICAM-3.
AB  - To analyze the binding requirements of LFA-1 for its two most homologous ligands,
      ICAM-1 and ICAM-3, we compared the effects of various LFA-1 activation regimes
      and a panel of anti-LFA-1 mAbs in T cell binding assays to ICAM-1 or ICAM-3
      coated on plastic. These studies demonstrated that T cell binding to ICAM-3 was
      inducible both from the exterior of the cell by Mn2+ and from the interior by an
      agonist of the "inside-out" signaling pathway. T cells bound both ICAM ligands
      with comparable avidity. A screen of 29 anti-LFA-1 mAbs led to the identification
      of two mAbs specific for the alpha subunit of LFA-1 which selectively blocked
      adhesion of T cells to ICAM-3 but not ICAM-1. These two mAbs, YTH81.5 and
      122.2A5, exhibited identical blocking properties in a more defined adhesion assay
      using LFA-1 transfected COS cells binding to immobilized ligand. Blocking was not
      due to a steric interference between anti-LFA-1 mAbs and N-linked carbohydrate
      residues present on ICAM-3 but not ICAM-1. The epitopes of mAbs YTH81.5 and
      122.2A5 were shown to map to the I domain of the LFA-1 alpha subunit. A third I
      domain mAb, MEM-83, has been previously reported to uniquely activate LFA-1 to
      bind ICAM-1 (Landis, R. C., R. I. Bennett, and N. Hogg. 1993. J. Cell Biol.
      120:1519-1527). We now show that mAb MEM-83 is not able to stimulate binding of T
      cells to ICAM-3 over a wide concentration range. Failure to induce ICAM-3 binding
      by mAb MEM-83 was not due to a blockade of the ICAM-3 binding site on LFA-1. This
      study has demonstrated that two sets of functionally distinct mAbs recognizing
      epitopes in the I domain of LFA-1 are able to exert differential effects on the
      binding of LFA-1 to its ligands ICAM-1, and ICAM-3. These results suggest for the
      first time that LFA-1 is capable of binding these two highly homologous ligands
      in a selective manner and that the I domain plays a role in this process.

PMID- 7518467
TI  - Stress relaxation of fibroblasts activates a cyclic AMP signaling pathway.
AB  - Mechanical force regulates gene expression and cell proliferation in a variety of
      cell types, but the mechanotransducers and signaling mechanisms involved are
      highly speculative. We studied the fibroblast signaling mechanism that is
      activated when cells are switched from mechanically stressed to mechanically
      relaxed conditions, i.e., stress relaxation. Within 10 min after initiation of
      stress relaxation, we observed a transient 10-20-fold increase in cytoplasmic
      cyclic AMP (cAMP) and a threefold increase in protein kinase A activity. The
      increase in cAMP depended on stimulation of adenylyl cyclase rather than
      inhibition of phosphodiesterase. Generation of cAMP was inhibited by
      indomethacin, and release of arachidonic acid was found to be an upstream step of
      the pathway. Activation of signaling also depended on influx of extracellular
      Ca2+ because addition of EGTA to the incubations at concentrations just
      sufficient to exceed Ca2+ in the medium inhibited the stress relaxation-dependent
      increase in free arachidonic acid and cAMP. This inhibition was overcome by
      adding CaCl2 to the medium. On the other hand, treating fibroblasts in
      mechanically stressed cultures with the calcium ionophore A23187-stimulated
      arachidonic acid and cAMP production even without stress relaxation. In summary,
      our results show that fibroblast stress relaxation results in activation of a
      Ca(2+)-dependent, adenylyl cyclase signaling pathway. Overall, the effect of
      stress relaxation on cAMP and PKA levels was equivalent to that observed after
      treatment of cells with forskolin.

PMID- 7518472
TI  - Impact of developmental problems on young children's exits from foster care.
AB  - Children entering foster care are often described as having multiple problems,
      although there are surprisingly few comprehensive baseline descriptions of
      children as they enter care. Further, few studies have examined the interactions
      among baseline characteristics, physical and mental health problems, and their
      joint influence on the likelihood that a child will remain in care. The purpose
      of this study was to investigate the relationship of physical and developmental
      problems identified shortly after the children entered substitute care to the
      likelihood of their remaining in care. Data for these analyses came from 272
      children (ages 1 month to 7 years) seen at the Foster Care Clinic in Waterbury,
      Connecticut, between November 1985 and December 1989. All children received a
      complete physical health assessment and developmental screening upon entry into
      care. The outcome variable, children's placement status as of September 1990, was
      confirmed through the Social Services Agency's records. Results indicate that
      children in foster care commonly showed developmental delays (53%). Further,
      those who were older at entry into care and nonwhite and who had developmental
      problems identified were 1.93 times more likely to remain in foster care. Given
      these findings, early comprehensive assessment for children entering foster care
      is strongly recommended.

PMID- 7518473
TI  - Developmental delay in healthy premature infants at age two years: implications
      for early intervention.
AB  - Ninety-four healthy full-term and preterm infants, who differed because of
      immaturity, not medical or social risk factors, were assessed at 3 and 24 months
      of age. Preterm infants scored significantly lower on the Bayley Mental
      Development Index (MDI), but not the Psychomotor Development Index (PDI) compared
      with full-term infants at 24 months (age corrected for prematurity). Nine
      factors, which included a combination of environmental and infant temperament
      variables, accounted for 36% of the variance in MDI scores. Separate regression
      analyses by infant group found that the caregiving environment, Home Observation
      for the Measurement of the Environment (HOME total score), contributed more to
      the variance in preterm than full-term development, despite the fact that the
      HOME scores were high and did not differ between groups at 2 years of age. These
      findings provide further evidence of the need to continue developmental follow-up
      for healthy low birth weight (LBW) preterm infants and of the important influence
      of early caregiving factors on later development, even for middle-class, LBW
      preterm infants.

PMID- 7518470
TI  - Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and
      transient tyrosine kinase activity.
AB  - The molecular mechanisms whereby hyaluronan (HA) stimulates cell motility was
      investigated in a C-H-ras transformed 10T 1/2 fibroblast cell line (C3). A
      significant (p < 0.001) stimulation of C3 cell motility with HA (10 ng/ml) was
      accompanied by an increase in protein tyrosine phosphorylation as detected by
      anti-phosphotyrosine antibodies using immunoblot analysis and immunofluorescence
      staining of cells. Tyrosine phosphorylation of several proteins was found to be
      both rapid and transient with phosphorylation occurring within 1 min of HA
      addition and dissipating below control levels 10-15 min later. These responses
      were also elicited by an antibody generated against a peptide sequence within the
      HA receptor RHAMM. Treatment of cells with tyrosine kinase inhibitors (genistein,
      10 micrograms/ml or herbimycin A, 0.5 micrograms/ml) or microinjection of anti
      phosphotyrosine antibodies inhibited the transient protein tyrosine
      phosphorylation in response to HA as well as prevented HA stimulation of cell
      motility. To determine a link between HA-stimulated tyrosine phosphorylation and
      the resulting cell locomotion, cytoskeletal reorganization was examined in C3
      cells plated on fibronectin and treated with HA or anti-RHAMM antibody. These
      agents caused a rapid assembly and disassembly of focal adhesions as revealed by
      immunofluorescent localization of vinculin. The time course with which HA and
      antibody induced focal adhesion turnover exactly paralleled the induction of
      transient protein tyrosine phosphorylation. In addition, phosphotyrosine staining
      colocalized with vinculin within structures in the lamellapodia of these cells.
      Notably, the focal adhesion kinase, pp125FAK, was rapidly phosphorylated and
      dephosphorylated after HA stimulation. These results suggest that HA stimulates
      locomotion via a rapid and transient protein tyrosine kinase signaling event
      mediated by RHAMM. They also provide a possible molecular basis for focal
      adhesion turnover, a process that is critical for cell locomotion.

PMID- 7518469
TI  - Cell surface annexin II is a high affinity receptor for the alternatively spliced
      segment of tenascin-C.
AB  - We have investigated the binding of soluble tenascin-C (TN-C) to several cell
      lines using a radioligand binding assay. Specific binding was demonstrated to U
      251MG human glioma cells and to a line of bovine aortic endothelial cells, but
      hamster fibroblasts showed no specific binding. Recombinant proteins
      corresponding to specific domains of TN-C were used to map the binding site(s) in
      TN-C. The alternatively spliced segment (TNfnA-D) inhibited the binding of native
      TN-C most strongly, and itself bound to glioma and endothelial cells. Scatchard
      analysis of TNfnA-D binding indicated 2-5 x 10(5) binding sites per cell, with an
      apparent 2 nM dissociation constant. The cell surface receptor for TNfnA-D was
      identified as a 35-kD protein on the basis of blot binding assays and affinity
      chromatography of membrane extracts on native TN-C and TNfnA-D columns. Protein
      sequencing indicated that this 35-kD receptor was annexin II. Annexin II is well
      characterized as a cytoplasmic protein, so it was surprising to find it as a
      presumably extracellular receptor for TN-C. To confirm that it was the 35-kD
      receptor, we obtained purified annexin II and demonstrated its binding to TNfnA-D
      and TN-C at nM concentrations. Antibodies to annexin II prominently stained the
      external surface of live endothelial cells and blocked the binding of TNfnA-D to
      the cells. Thus annexin II appears to be a receptor for the alternatively spliced
      segment of TN-C, and may mediate cellular responses to soluble TN-C in the
      extracellular matrix.

PMID- 7518474
TI  - Distinct spatiotemporal expressions of five NMDA receptor channel subunit mRNAs
      in the cerebellum.
AB  - The distribution of five NMDA receptor channel subunit mRNAs was examined in the
      mouse cerebellum from embryonic day 13 through postnatal day 56, by in situ
      hybridization with subunit-specific oligonucleotide probes. At postnatal days 21
      and 56, each cerebellar neuron displayed differential expressions of the epsilon
      subunit mRNAs. The granule cells showed hybridizing signals for the epsilon 1 and
      epsilon 3 subunit mRNAs, the molecular layer neurons for the epsilon 4 subunit
      mRNA, and the cerebellar nucleus neurons for the epsilon 1 and epsilon 4 subunit
      mRNAs, whereas the Purkinje cells did not express any epsilon subunit mRNAs. At
      early postmitotic stages of development, the epsilon 2 subunit mRNA appeared in
      each cerebellar neuron, including the Purkinje cells, and the epsilon 4 subunit
      mRNA appeared in neurons of the molecular layer and the cerebellar nuclei. The
      expression patterns in the cerebellum altered drastically during the first 2
      postnatal weeks; the epsilon 1 and epsilon 3 subunit mRNAs appeared in the
      granule cells and the cerebellar nucleus neurons, whereas the epsilon 2 subunit
      mRNA disappeared from each neuron and the signal levels of the epsilon 4 subunit
      mRNA decreased remarkably. In contrast to the differential expressions of the
      four epsilon subunit mRNAs, intense signals for the zeta 1 subunit mRNA were
      observed in each cerebellar neuron from early postmitotic stages through the
      mature stage. These findings suggest that anatomical organization of the epsilon
      subunits is heterogeneous in the cerebellum both spatially and temporally, which
      would give rise to functional diversity of the NMDA receptor channel.

PMID- 7518476
TI  - Serotoninergic innervation of nonprincipal cells in the cerebral cortex of the
      lizard Podarcis hispanica.
AB  - The mechanism of serotoninergic transmission in the neo- and archicortex of
      mammals is complex, including both synaptic and nonsynaptic components, direct
      actions on principal cells, and indirect effects mediated by GABAergic
      interneurons. Here we studied the termination pattern and synaptic organization
      of the serotoninergic afferents in the cerebral cortex of the lizard, Podarcis
      hispanica, which is considered to correspond in part to the mammalian hippocampal
      formation, with the aim of unraveling basic, phylogenetically preserved rules in
      the connectivity of this pathway. We demonstrate that serotoninergic afferents,
      visualized by immunostaining for serotonin itself, establish multiple synaptic
      contacts with different subpopulations of nonprincipal cells containing
      parvalbumin, neuropeptide Y, and opioid peptides. The former two subpopulations
      contain GABA, whereas the opioid-immunoreactive neurons are most likely GABA
      negative cells. Evidence is provided at the electron microscopic level that
      serotonin-immunoreactive varicosities establish conventional asymmetric synaptic
      contacts with their nonprincipal targets, but nonsynaptic varicosities also
      exist. We conclude that, similarly to mammals, a selective synaptic innervation
      of nonprincipal, possibly inhibitory, neurons is among the mechanisms of
      serotoninergic modulation of cerebral cortical activity in the lizard.

PMID- 7518475
TI  - Distinct distributions of five NMDA receptor channel subunit mRNAs in the
      brainstem.
AB  - The distribution of five NMDA receptor channel subunit mRNAs in the mouse
      brainstem at postnatal day 21 was semiquantitatively examined by in situ
      hybridization with subunit-specific oligonucleotide probes. The epsilon 1 subunit
      mRNA was observed in various brainstem nuclei. On the other hand, the epsilon 2
      and epsilon 3 subunit mRNAs were restricted to particular nuclei, and the epsilon
      4 subunit mRNA was detected in several nuclei at very low levels. The dorsal
      cochlear nucleus exhibited differential expression of the epsilon subunit mRNAs
      in distinct neuron types: the epsilon 2 subunit mRNA in the pyramidal cells, the
      epsilon 3 subunit mRNA in the granule cells, and the epsilon 1 subunit mRNA in
      other neurons. In the vestibular nuclei, the medial nucleus expressed the epsilon
      1, epsilon 3, and epsilon 4 subunit mRNAs, whereas the lateral and superior
      nuclei expressed the epsilon 1 subunit mRNA. Such region-specific expressions
      were also discerned in the central gray, the superior and inferior colliculi, the
      medial accessory oculomotor nucleus, the locus ceruleus, the parabrachial
      nucleus, nucleus of the solitary tract, the caudal subnucleus of the trigeminal
      spinal tract nucleus, and the inferior olive. In contrast to the differential
      distributions of the four epsilon subunit mRNAs, intense signals for the zeta 1
      subunit mRNA were distributed throughout the brainstem. These findings suggest
      that anatomical organization of the epsilon subunits is heterogeneous in various
      regions of the brainstem, which would give rise to functional diversity of the
      NMDA receptor channel in these regions.

PMID- 7518477
TI  - Benign lymphangioendothelioma.
AB  - We describe a 40-year-old white man with a red-brown, indurated plaque on the
      proximal aspect of his right thigh. The lesion had been present since birth, and
      the patient had a 20-year clinical history of recurrent cellulitis in the same
      area. The histopathologic features of the lesion included permeation of the
      dermis by flattened, endothelium-lined channels without cellular atypia,
      hemorrhage, or inflammation. The endothelial cells were stained intensely with
      monoclonal antibody anti-CD34 (clone MY10). In addition, antibodies to factor
      VIII antigen, HLA-DR, smooth muscle actin, ICAM-1, and the lectin Ulex europaeus
      labeled the luminal cells. The basement membrane of the channels stained with
      anti-type IV collagen and laminin. Desmin-positive cells were abundant adjacent
      to the channels. Factor XIIIa stained both mononuclear cells and occasional
      dendritic cells in the perivascular area. Ki-67 immunolabeling could not be
      demonstrated on fresh or frozen tissue. Electron microscopy revealed the presence
      of both tight junctions and a well-formed, continuous basement membrane but the
      absence of Weibel-Palade bodies.

PMID- 7518478
TI  - Dying in palliative care units and in hospital: a comparison of the quality of
      life of terminal cancer patients.
AB  - A comparison of the quality of life of terminal cancer patients in two palliative
      care units with that of those in a general hospital is reported here. Quality of
      life was considered as a multidimensional concept. It was assessed for the 182
      patients by applying content analysis scales to transcripts of their responses to
      part of a standardized interview. A personal construct model of dying provided
      the specific hypotheses about differences in quality of life. Patients in
      specialized palliative care units were, as predicted, found to differ from those
      dying in hospital, showing less indirectly expressed anger but more positive
      feelings. They also reported more anxiety about death but less anxiety about
      isolation and general anxiety, and fewer influential and nonspecified shared
      relationships. Against prediction, the patients in the two specialized units were
      also found to differ from each other, those in the smaller unit showing more
      directly expressed anger and helplessness than those in the larger unit.

PMID- 7518479
TI  - Knowledge and presence: accountability as described by nurses and surgical
      patients.
AB  - Accountability was an integral part of phenomenological descriptions of 24
      patients' experience of having surgery and 24 nurses' understanding of their
      experiences. Patients and nurses discussed two major elements, knowledge and
      presence, although the emphasis on categories within these elements differed.
      Within the element of knowledge, nurses emphasized lacking knowledge, using
      professional knowledge, teaching, and leadership. Patients talked most about
      receiving teaching and individualized knowledge. Nurses also emphasized structure
      and process, and patients emphasized outcomes. Within the element of presence,
      nurses talked most about environmental barriers and interaction, and patients
      emphasized attentive attitude. This view of accountability may help restructure
      work environments to allow nurses to meet the needs that patients perceive
      themselves as having.

PMID- 7518480
TI  - Substance P potentiates the algogenic effects of intraarterial infusion of
      adenosine.
AB  - OBJECTIVES: This study investigated whether substance P potentiates the muscular
      and cardiac pain caused by the intraarterial infusion of adenosine, an autocoid
      known to induce muscular and cardiac ischemic-like pain in humans. BACKGROUND:
      Substance P is involved in the generation of neurogenic inflammation and causes
      cutaneous hyperalgesia. Because substance P is present in perivascular nerves it
      might also cause muscular and cardiac hyperalgesia. To test this hypothesis its
      effects on adenosine-induced muscular and cardiac pain were investigated in
      humans. METHODS: A randomized, crossover study of the algogenic effects of the
      intrailiac infusion of increasing scalar doses (from 125 to 2,000 micrograms/min)
      of adenosine or substance P (11.2 pmol/min) for 3 min, followed by the
      simultaneous infusion of substance P plus the same doses of adenosine, was
      carried out in nine patients with no evidence of peripheral vascular disease. A
      similar protocol was carried out by infusing increasing scalar doses of adenosine
      (from 50 to 800 micrograms/min) or substance P (11.2 pmol/min) for 3 min,
      followed by the simultaneous infusion of substance P plus the same doses of
      adenosine, into the left coronary artery of eight patients with angina. Pain
      severity, assessed by a visual analog scale, is presented as median. The
      remaining data are presented as mean value +/- 1 SD. RESULTS: All patients
      experienced pain during both adenosine and substance P plus adenosine infusion;
      no patient experienced pain during the infusion of substance P alone. During
      intrailiac infusion, all patients experienced pain in the right leg that occurred
      earlier (207 +/- 152 vs. 321 +/- 154 s, p < 0.05) and was greater (47 vs. 30 mm,
      p < 0.05) during the simultaneous infusion of substance P plus adenosine than
      during the infusion of adenosine. Similarly, during intracoronary infusion, all
      patients experienced chest pain that occurred earlier (409 +/- 242 vs. 596 +/-
      210 s, p < 0.05) and was greater (51 vs. 33 mm, p < 0.05) during the simultaneous
      infusion of substance P plus adenosine than during infusion of adenosine. No
      patient exhibited electrocardiographic signs of ischemia. CONCLUSIONS: Substance
      P does not cause muscular or cardiac pain, but it provokes muscular and cardiac
      hyperalgesia.

PMID- 7518481
TI  - Monoclonal antibodies prepared against the DNA polymerase from Thermus aquaticus
      are potent inhibitors of enzyme activity.
AB  - Recent interest in the unique properties of the DNA polymerase from Thermus
      aquaticus (TaqPol) has stemmed from its use in many laboratories for the
      polymerase chain reaction. We have produced a panel of nine distinct monoclonal
      antibodies to a recombinant form of TaqPol that have the following properties:
      (1) each binds TaqPol with high affinity (Kd < 10 nM); (2) eight of the nine
      arbitrarily selected monoclonal antibodies inhibit TaqPol activity completely;
      (3) the weak inhibitor is specific for TaqPol only while all eight strong
      inhibitors cross-react with the DNA polymerase from at least one other Thermus
      species as detected by either competitive ELISA, Western blotting, inhibition of
      enzyme activity or determination of binding by surface plasmon resonance; (4)
      these antibodies can be distinguished from each other by heavy chain class, cross
      reactivity patterns, isoelectric points, and epitope mapping; and (5) these
      antibodies define seven non-overlapping epitopes. In addition, we show data from
      a preliminary experiment that demonstrates that at least one of these antibodies
      inhibits TaqPol by preventing DNA binding.

PMID- 7518482
TI  - Enhanced immunogenicity of leucine enkephalin following coupling to anti
      immunoglobulin and anti-CD3 antibodies.
AB  - Leucine enkephalin (Leu-enk) was coupled to both T and B cell antibodies in order
      to investigate the possibility of enhanced immunogenicity via targeted
      immunization. The two antibodies used were Hm x Mo CD3 and Gt x Mo Ig,
      respectively. The data indicate that while both antibody carriers enhanced the
      immunogenicity of Leu-enk, the use of the Hm x Mo CD3 antibody resulted in a
      greater number of mice with positive Leu-enk specific serum titers. 12 Leu-enk
      cell lines were produced and one, LE4H8, was chosen for characterization.

PMID- 7518483
TI  - Conjugation of recombinant reverse transcriptase of HIV-1 to beta-D-galactosidase
      from Escherichia coli for ultrasensitive enzyme immunoassay (immune complex
      transfer enzyme immunoassay) of anti-HIV-1 IgG.
AB  - Recombinant reverse transcriptase (RT) of HIV-1 was conjugated to beta-D
      galactosidase from Escherichia coli in three different ways. Maleimide groups
      were introduced into beta-D-galactosidase molecules using N,N'-o
      phenylenedimaleimide in the absence (method I) or presence (method II) of N
      ethylmaleimide or into beta-D-galactosidase molecules, which had been treated
      with excess of 4,4'-dithiodipyridine to block thiol groups, using N-succinimidyl
      6-maleimidohexanoate (method III). Subsequently, the maleimide groups were
      reacted with thiol groups introduced into recombinant RT molecules using N
      succinimidyl-S-acetylmercaptoacetate. The conjugates were tested by a sensitive
      enzyme immunoassay (immune complex transfer enzyme immunoassay). The immune
      complex consisting of 2,4-dinitrophenyl-bovine serum albumin-recombinant RT
      conjugate, anti-HIV-1 IgG and recombinant RT-beta-D-galactosidase conjugate was
      captured by polystyrene beads coated with (anti-2,4-dinitrophenyl group) IgG,
      eluted with N epsilon-2,4-dinitrophenyl-L-lysine and transferred to polystyrene
      beads with (anti-human IgG gamma chain) IgG. The conjugate prepared by method
      III, which showed the least polymerization, the least loss of the specific enzyme
      activity and the lowest nonspecific binding, improved the sensitivity of the
      enzyme immunoassay for anti-HIV-1 IgG approximately 30-fold compared with RT
      horseradish peroxidase conjugate.

PMID- 7518484
TI  - Use of hu-IgG-SCID mice to evaluate the in vivo stability of human monoclonal IgG
      antibodies.
AB  - Human and in vitro modified mAbs such as humanized rodent mAbs and immunotoxins
      are now considered for a variety of applications in humans. The adequate in vivo
      stability of these Ig preparations is not easily predicted from in vitro studies
      and may be essential for many therapeutic applications. In this study, we report
      the development and characterization of an in vivo model for testing this
      parameter using SCID mice containing a physiological concentration of human IgG
      (hu-IgG-SCID). The model was tested with several IgG1 and IgG3 human mAbs
      reacting with the human Rh(D) red cell antigen. It is known that human IgG have a
      shorter half-life in SCID mice than in humans. However, our results showed that
      the half-life of IgG3 mAbs (1.5 +/- 0.5 days) was much shorter than the one of
      IgG1 mAbs (5.8 +/- 1.4 days), indicating that the relative stability of IgG1 and
      IgG3 human mAbs in hu-IgG-SCID mice is similar to the one previously reported in
      humans (21 days vs. 7 days respectively). The IgG catabolism rate in humans is
      known to be inversely proportional to serum IgG concentrations. Accordingly, the
      dilution of the mAbs in a large excess (200-fold) of human IgG was found to be an
      important parameter of the hu-IgG-SCID mouse model since much longer (3-4-fold)
      mAb half-lives were obtained in the presence of a lower dose or in the absence of
      co-injected human IgG. This study show the usefulness of this animal model for
      the evaluation of human antibody stability in an in vivo environment.

PMID- 7518485
TI  - CARE-LASS (calcein-release-assay), an improved fluorescence-based test system to
      measure cytotoxic T lymphocyte activity.
AB  - CARE-LASS is a highly sensitive, fast, simple and safe fluorometric microassay.
      Target cells are loaded with acetoxymethyl ester of calcein (calcein-AM) that
      passively crosses the cell membrane. Intracellular esterases convert the molecule
      to calcein, a polar fluorochrome which, in cells with intact plasma membranes,
      displays good retention characteristics and low pH sensitivity. In analogy to
      standard 51Cr release assays, the CARE-LASS system is based on the release of a
      marker into the supernatant that is measured by an automated fluorescence scanner
      and correlates with the number of lysed cells. We tested the CARE-LASS system by
      measuring cytotoxicity in major histocompatibility complex (MHC) class I and MHC
      class II restricted cytotoxic T lymphocyte (CTL) assays as well as lymphokine
      activated killer (LAK) mediated cytotoxicity. We applied a small set of target
      cell lines at various effector to target (E:T) ratios, at different antigen
      concentrations and compared CARE-LASS CTL data to data resulting from
      conventional 51Cr release assays. The CARE-LASS system provides a reliable and
      sensitive method to measure cell-mediated cytotoxicity.

PMID- 7518486
TI  - Scanning for T helper epitopes with human PBMC using pools of short synthetic
      peptides.
AB  - Major T helper epitopes of medically important antigens can be located by
      measuring the proliferative responses of human peripheral blood mononuclear cells
      (PBMC) to pools of short synthetic peptides. The length and endings of the
      peptides used were shown to be critical for success in identifying Th cell
      epitopes. Many epitopes would be missed if either long (31mers) or short (less
      than 12mers) peptides were used. Pools of 14 and 16mers were more efficient than
      12mers spanning the same region, however, for a promiscuous Th cell epitope of
      tetanus toxin (tt 947-967), two of three donors tested did not respond to 18mers
      or shorter peptides spanning this region. Although peptides with either unblocked
      or blocked ends were stimulatory, peptides with blocked ends were generally more
      efficient. The peptide concentration and number of available APC were also found
      affect the efficiency of the proliferation assay as a measure of peptide
      recognition by Th cells. Two screenings of the entire set of tetanus toxin
      peptide pools using different samples of PBMC from the same donor identified
      common major stimulatory regions. Thus, PBMC and peptide pools can be used for
      the reproducible identification of Th cell epitopes. After immunization with
      tetanus toxoid (TT), peptide-responsive cells increased in frequency in parallel
      to the increase in TT responsive cells, indicating that the peptide-responsive
      cells were primed by TT.

PMID- 7518487
TI  - Synergy test for recognition of epitopes on soluble proteins; its application in
      the study of CD21 and CD23 antigens and their respective antibodies.
AB  - Antigens such as CD21 and CD23, which express only one copy of an epitope require
      two monoclonal antibodies (mAbs) for their detection and estimation. This
      requirement is exploited in two ways in a technique based on the chromic chloride
      haemagglutination test. For simple titration of antigen two portions of red cells
      each coated with one of a pair of synergising mAbs are used in a 1:1 combination.
      For testing the antigenic specificity of a mAb and assessing its region of
      epitope binding, the mAb under test is serially diluted in fluid containing a
      standard amount of antigen and red cells are added to which have been attached a
      different mAb. If the red cell-bound mAb recognises a determinant topographically
      distinct from that of the soluble mAb, red cell agglutination to high titre
      occurs. In titrations of ascitic fluid containing approximately 1 mg/ml mAb,
      titres of log2(9) to log2(16) were recorded from a starting dilution of 1 in 200.
      Hence the test is very sensitive and only minute amounts of a mAb are required
      for testing. The same test system can be used for assessing the relative display
      of epitopes on antigen obtained from different sources, e.g., culture supernates
      and body fluids. The method is of general applicability to monomeric antigens and
      its use is illustrated by analysis of CD21 and CD23 antigens and antibodies.

PMID- 7518489
TI  - Hepatitis C virus (HCV) viremia in human immunodeficiency virus-seronegative and 
      seropositive patients with indeterminate HCV recombinant immunoblot assay.
AB  - Positivity of recombinant immunoblot assay (RIBA) for detection of antibodies to
      hepatitis C virus (anti-HCV) is usually associated with HCV viremia. The
      significance of an indeterminate RIBA result, defined by reactivity to only one
      HCV antigen, is unclear. Whether anti-human immunodeficiency virus (HIV)-negative
      or -positive subjects with an indeterminate RIBA have HCV viremia detectable by
      polymerase chain reaction was investigated. An indeterminate RIBA was found in 48
      (15%) of 318 anti-HIV-negative and 38 (23%) of 167 anti-HIV-positive subjects (P
      < .05). Clinical stage was IV-C-1 or IV-C-2 in 82% of those anti-HIV-positive.
      HCV viremia was found more frequently in anti-HIV-positive (89%) than in anti-HIV
      negative subjects (50%) with an indeterminate RIBA (P < .05). These results
      suggest an impaired anti-HCV response associated with HIV infection.

PMID- 7518490
TI  - Measurement of mandibular bone density after iliac crest grafting.
AB  - Nonvascularized and microsurgically revascularized iliac bone grafts used for
      mandibular reconstruction behave differently during healing. Quantitative
      computer tomography (QCT) was used to investigate these differences with respect
      to mineralization and macrostructure of the grafts after a period of adequate
      functional loading. It was shown that in nonvascularized grafts, reactive
      sclerosis occurs, as a sign of an irregularly reparative metaplastic process and
      mineralization. In comparison with the intact iliac crest, the bone density of
      the graft was markedly increased. The microsurgically revascularized grafts,
      however, showed retention of structural differentiation into homogeneous
      cancellous bone, and a smoothly demarcated cortex with essentially unchanged bone
      density. Possible explanations of these differences are discussed.

PMID- 7518488
TI  - Role of hepatitis C and delta viruses in the termination of chronic hepatitis B
      surface antigen carrier state: a multivariate analysis in a longitudinal follow
      up study.
AB  - Influences of hepatitis delta (HDV) or C virus (HCV) superinfection on the
      spontaneous clearance of hepatitis B virus (HBV) surface antigen (HBsAg) were
      investigated in 992 patients. Patients were infected with HBV alone (group 1),
      HBV and HDV (group 2), HBV and HCV (group 3), or all three viruses (group 4).
      They were followed for 6.2 +/- 3.7 years. Thirty-six patients (3.6%) had
      spontaneous serum HBsAg clearance. There was an increasing linear trend in the
      annual incidence from 0.43% (group 1) to 0.64% (group 2), 2.08% (group 3), and
      2.33% (group 4; P < .0001). Relative risk (RR) of group 3 to 1 was 4.8 (P < .001)
      and of group 4 to 1 was 5.1 (P < .02). RR was significantly higher in group 3
      than 2 (P < .02). By Cox multivariate regression analysis, only HCV
      superinfection and age at entry were significant influencing factors. Moreover,
      there was a significant interaction between HCV and age. Patients > 35 years old
      with HCV had a higher HBsAg clearance rate. Results suggest that HCV is the most
      important hepatotropic virus that enhances HBsAg clearance in chronic hepatitis
      B.

PMID- 7518493
TI  - The detection of amylase on swabs from sexual assault cases.
AB  - Results are presented of amylase tests performed on more than 400 casework swabs
      using Phadebas tablets. Amylase levels indicative of saliva were obtained from
      25% of the penile swabs tested, 32% of the vaginal swabs and 50% of the breast
      swabs. The longest time interval between the offence and sampling when such
      levels were detected was 16 hours for penile swabs, 55 hours for vaginal swabs
      and 30 hours for breast swabs.

PMID- 7518494
TI  - Coordinate regulation of choline acetyltransferase, tyrosine hydroxylase, and
      neuropeptide mRNAs by ciliary neurotrophic factor and leukemia inhibitory factor
      in cultured sympathetic neurons.
AB  - The neurotransmitter phenotype switch that occurs in cultures of rat superior
      cervical ganglion neurons after treatment with leukemia inhibitory factor or
      ciliary neurotrophic factor is a useful model permitting investigation of the
      mechanisms of cytokine-mediated differentiation. Recently the actions of leukemia
      inhibitory factor and ciliary neurotrophic factor have been linked through their
      interactions with related receptor complexes. Here we compare the effects of
      these two cytokines on gene expression in sympathetic neuronal cultures and begin
      to investigate their mechanisms. We report that, as has been shown for leukemia
      inhibitory factor, ciliary neurotrophic factor regulates peptides and classical
      transmitters in these cultures at the mRNA level. In addition, we find that the
      induction of substance P mRNA by these cytokines is rapid, dependent on protein
      synthesis, and occurs in 40-50% of superior cervical ganglion neurons in
      dissociated culture.

PMID- 7518492
TI  - Platelet activation during hemodialysis measured through exposure of p-selectin:
      analysis by flow cytometric and ultrastructural techniques.
AB  - P-selectin is a platelet protein in alpha-granules that is expressed on their
      membranes after platelet activation. Using a specific monoclonal antibody (RUU
      2.17), we have studied platelet activation during hemodialysis with a cuprophan
      membrane in eight patients with uremia. Blood samples were obtained before
      hemodialysis from venipuncture (sample I), at the beginning of the hemodialysis
      from the arterial (sample II) and venous lines (sample III), and after 2 hours of
      hemodialysis from the venous line (sample IV). Exposure of P-selectin on platelet
      surface was studied by flow cytometry, and morphologic and immunocytochemical
      studies were performed. No differences in P-selectin expression were observed by
      single-labeling flow cytometry in samples I, II, and IV. However, a significant
      increase in fluorescence occurred in sample III (percentage of positive platelets
      [%PP], 18.0% +/- 6.1%) with respect to sample I (%PP, 6.9% +/- 2.0%; p < 0.01).
      An apparently decreased fluorescence was seen in sample IV (%PP, 8.8% +/- 3.9%)
      with respect to sample III. Double-labeling flow cytometry showed statistically
      significant differences between sample I (%PP, 7.1% +/- 2.6%) and sample III
      (%PP, 19.4% +/- 9.4%; p < 0.01) and IV (%PP, 19.0% +/- 10.1%; p < 0.01), but not
      between samples III and IV. The ultrastructural study revealed an increasing
      number of platelet morphologic signs of activation throughout the period of
      hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518491
TI  - Plasma levels and urinary excretion of fibrinolytic and protease inhibitory
      proteins in nephrotic syndrome.
AB  - Nephrotic syndrome is associated with numerous blood coagulation abnormalities
      and a marked propensity to thromboembolism. The present study was undertaken to
      examine the status of the fibrinolytic system in this hypercoagulable state. We
      measured the antigen concentrations or activities of plasminogen, tissue-type
      plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), alpha 2
      antiplasmin, alpha 1-antitrypsin, and alpha 2-macroglobulin as well as total
      antiplasmin activity and D-dimer concentration in the plasma of 39 patients with
      nephrotic syndrome and 32 normal controls subjects. In addition, antigen
      concentrations of plasminogen, alpha 2-antiplasmin, alpha 1-antitrypsin, and
      alpha 2-macroglobulin were measured in the urine of the study populations. The
      nephrotic group showed marked elevations of plasma t-PA, plasminogen, alpha 2
      macroglobulin, and D-dimer and a significant reduction of plasma alpha 2
      antiplasmin and alpha 1-antitrypsin as compared with the normal control group.
      Plasma alpha 2-macroglobulin was directly related to 24-hour urinary protein
      excretion and inversely related to serum albumin concentration. None of the
      proteins measured were detectable in the urine of normal controls. However,
      substantial amounts of plasminogen, alpha 2-antiplasmin, and alpha 1-antitrypsin
      and small amounts of alpha 2-macroglobulin were recovered in the urine of
      patients with nephrotic syndrome. Despite the lack of clinically demonstrable
      thrombosis, plasma D-dimer was markedly elevated in the nephrotic group,
      suggesting concurrent activation of coagulation and fibrinolytic pathways. In
      addition, the study revealed multiple abnormalities of the plasma fibrinolytic
      proteins and documented their urinary excretion in patients with nephrotic
      syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518495
TI  - Immunological detection of isoforms of the somatostatin receptor subtype, SSTR2.
AB  - Somatostatin (SRIF) induces its diverse physiological actions through
      interactions with different receptor subtypes. Multiple SRIF receptor subtypes
      have recently been cloned. To analyze the physical properties of receptor subtype
      SSTR2, two different peptide-directed antibodies were generated against SSTR2.
      Antibody "2e3," directed against the peptide SSCTINWPGESGAWYT (residues 191-206),
      corresponding to a region in the predicted third extracellular domain of mouse
      SSTR2, and antibody "2i4," directed against the peptide SGTEDGERSDS (residues 333
      343) from the predicted cytoplasmic tail of mouse SSTR2, were developed. In
      Chinese hamster ovary (CHO) cells stably expressing the mouse SSTR2 gene (CHOB),
      the antibody 2e3 recognized specifically a protein of 93-kDa protein by
      immunoblotting. No specific immunoreactivity was detected by 2e3 in
      nontransfected CHO cells or CHO cells stably expressing vector alone or human
      SSTR1 or mouse SSTR3 genes. The antibody 2i4 specifically immunoprecipitated
      SSTR2 solubilized from CHOB cells that could be labeled with the SSTR2-specific
      ligand 125I-MK-678. Furthermore, both 2e3 and 2i4 specifically immunoprecipitated
      93-kDa [35S]methionine-labeled proteins from CHOB cells, indicating that they
      recognize the same proteins. In contrast to studies in CHOB cells, immunoblotting
      studies showed that 2e3 detected specifically a single 148-kDa protein from
      different regions of the rat brain that have previously been shown to express
      high levels of SSTR2 mRNA and SRIF receptors with high affinity for 125I-MK-678.
      In contrast, no immunoreactivity was detected in rat kidney, liver, or lung,
      which do not express SSTR2. No 93-kDa protein was detected specifically in the
      rat brain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518496
TI  - Cloning and expression of a 5-hydroxytryptamine7 receptor positively coupled to
      adenylyl cyclase.
AB  - A cDNA clone (designated as GP2-7) encoding a novel 5-hydroxytryptamine (5-HT)
      receptor was isolated from a guinea pig hippocampal library. The receptor shares
      amino acid homology within the hydrophobic domains with other cloned 5-HT
      receptor subtypes (34-48%). The sequence of GP2-7 is homologous to that described
      for a novel receptor previously cloned from a rat brain cDNA library and
      provisionally designated as 5-HT7. mRNA for GP2-7 was detected in cortical and
      limbic brain regions. Transiently expressed GP2-7 showed high-affinity binding to
      [3H]5-HT (pKi = 9.0) with the following rank order of affinities: 5
      carboxyamidotryptamine (5-CT) > 5-HT = 5-methoxytryptamine (5-MeOT) >
      methiothepin > 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) > spiperone >>
      sumatriptan. Adenylyl cyclase activity in CHO-K1 cells transiently transfected
      with GP2-7 was stimulated by several analogues of 5-HT with the following order
      of potency: 5-CT > 5-HT = 5-MeOT > dipropyl-5-CT > 8-OH-DPAT. Methiothepin and
      spiperone were potent antagonists. Preliminary analysis suggests that GP2-7
      closely resembles a receptor in the guinea pig hippocampus that exhibits a high
      affinity toward 5-CT.

PMID- 7518498
TI  - Synergistic activation of DNA synthesis in astrocytes by fibroblast growth
      factors and extracellular ATP.
AB  - The effects of extracellular ATP and polypeptide growth factors on DNA synthesis
      in primary cultures of rat astrocytes have been examined. It was found that ATP
      acts synergistically with either acidic or basic fibroblast growth factor to
      stimulate DNA synthesis. The specificity of this effect was demonstrated by the
      inability of ATP to potentiate DNA synthesis induced by platelet-derived growth
      factor or epidermal growth factor. ATP appears to act via P2 purinergic
      receptors, because (a) it was more effective than adenosine and (b) the
      synergistic effect was observed with the hydrolysis-resistant P2 agonists, ADP
      beta S and ATP gamma S. The evidence suggests that extracellular ATP may be an
      important factor in regulating the extent of gliosis and, as such, may be
      involved in mechanisms of neural injury and repair.

PMID- 7518499
TI  - Expression of neurotrophins and their receptors in primary astroglial cultures:
      induction by cyclic AMP-elevating agents.
AB  - By northern blot analysis and ribonuclease protection assay, we observed the
      presence of a high level of trkB mRNA in primary brain cultures devoid of
      neuronal cells and highly enriched in glial fibrillary acidic protein-positive
      astroglial cells prepared from newborn rat cerebral hemispheres, cerebral cortex,
      hippocampus, and striatum. In primary astroglial cultures, the more abundant trkB
      transcripts code for the truncated receptor without tyrosine kinase activity;
      probes specific for the full-length trkB mRNA did not detect any signal in
      northern blot analysis. By the sensitive ribonuclease protection assay, we could
      show the presence of trkC mRNA in cultured astrocytes, whereas no trkA mRNA was
      detected. We confirmed the presence of relatively high levels of nerve growth
      factor and neurotrophin-3 mRNA, and very low basal level of brain-derived
      neurotrophic factor mRNA. Moreover, we demonstrated that another member of the
      neurotrophin family, neurotrophin-4, is also expressed in cultured astroglial
      cells. In view of the fact that many functional receptors for conventional
      neurotransmitters or neuropeptides present on astroglial cells may act via the
      adenylate cyclase system, we studied also the effect of agents able to increase
      the intracellular cyclic AMP concentration. A sharp increase in the trkB mRNA
      level was observed after treatment of primary astroglial cultures with dibutyryl
      cyclic AMP, 8-bromo-cyclic AMP, or the phosphodiesterase inhibitor, 3-isobutyl-1
      methylxanthine. On the contrary, trkC mRNA levels were unaffected by treatment
      with cyclic AMP-elevating agents. All the neurotrophin mRNAs examined, except
      neutrophin-4, were increased by 3-isobutyl-1-methylxanthine treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7518503
TI  - Glutamatergic control of dopamine release during stress in the rat prefrontal
      cortex.
AB  - In vivo microdialysis was used to assess the hypothesis that the stress-induced
      increase in dopamine release in the prefrontal cortex is mediated by stress
      activated glutamate neurotransmission in this region. Local perfusion of an alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor
      antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, blocked the stress-induced
      increase in dopamine levels, whereas an NMDA receptor antagonist, 2-amino-5
      phosphonopentanoic acid, at the dose tested, was not able to alter this response
      significantly. These data indicate that the effect of stress on dopamine release
      in the prefrontal cortex is mediated locally by activation of AMPA/kainate
      receptors, which modulate the release of dopamine in this region.

PMID- 7518502
TI  - Membrane topology of the GluR1 glutamate receptor subunit: epitope mapping by
      site-directed antipeptide antibodies.
AB  - In order to define the membrane topology of the GluR1 glutamate receptor subunit,
      we have examined the location of epitopes. Antibodies were produced against
      peptides corresponding to putative extracellular and intracellular segments of
      the rat brain GluR1 glutamate receptor subunit. Immunocytochemistry at the
      electron microscopic level in the dentate gyrus of the hippocampal formation
      showed that epitopes for the antiserum to the N-terminal part of the subunit are
      located at the extracellular face of the plasma membrane, whereas the antigenic
      determinants for the antiserum to the C-terminal part are found at the
      intracellular face of the postsynaptic membrane. Furthermore, antibodies to the N
      terminal residues 253-267 reacted similarly with both intact and permeabilized
      synaptosomes, whereas the binding of antibodies to the C-terminal residues 877
      889 increased about 1.6-fold following permeabilization. Our data suggest that
      the N- and C-terminal regions are located on the opposite side of the membrane
      and, therefore, the GluR1 subunit probably has an odd number of membrane spanning
      segments. The antibody cross-reactivities in different species and their effect
      on ligand binding activity were also established.

PMID- 7518497
TI  - Expression of non-NMDA glutamate receptor channel genes by clonal human neurons.
AB  - Treatment of the human teratocarcinoma line NTera2/c1.D1 (NT2) with retinoic acid
      induces terminal neuronal differentiation. In a previous study, we found that the
      neurons obtained in this way express functional N-methyl-D-aspartate (NMDA) and
      non-NMDA glutamate receptor channels. We now show by reverse transcriptase
      polymerase chain reaction and Southern blotting that these neurons transcribe
      each of the nine known non-NMDA glutamate receptor genes (GluR1-7, Ka-1, and Ka
      2) and that four of these genes (GluR2, GluR6, GluR7, and Ka-1) are also
      transcribed by undifferentiated NT2 cells. Patch clamp studies demonstrate that
      individual non-NMDA glutamate receptor channels are readily isolated from NT2
      derived neurons and that these channels are potently modulated by the
      desensitization blocker cyclothiazide. NT2-derived neurons are susceptible to
      kainate excitotoxicity but are not injured by prolonged exposure to alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate. We expect that the NT2-derived human
      neuronal culture system will facilitate studies of human neuronal non-NMDA
      glutamate receptor channels and of the pathophysiology of neuronal
      excitotoxicity.

PMID- 7518500
TI  - Increased extracellular serotonin in rat brain after systemic or intraraphe
      administration of morphine.
AB  - The effect of morphine on serotonin (5-HT) and 5-hydroxyindoleacetic acid (5
      HIAA) in the CNS of unanesthetized rats was investigated by microdialysis.
      Morphine was administered either subcutaneously, by local perfusion into the
      diencephalon, or by intraraphe microinjection. Systemic administration of
      morphine resulted in a significant increase in both extracellular 5-HT and 5-HIAA
      in the diencephalon. The effect of morphine on 5-HT was dose dependent during
      local perfusion of the diencephalon with inhibitors of uptake or monoamine
      oxidase. Systemic morphine also produced significant increases in extracellular 5
      HT in the striatum and hippocampus during uptake inhibition. The site of opioid
      effects on 5-HT was tested by locally perfusing morphine into the diencephalon.
      This had no effect on 5-HT or 5-HIAA. In contrast, intraraphe injection of
      morphine caused a dose-dependent increase in extracellular 5-HT and 5-HIAA in the
      diencephalon. These results suggest that systemic morphine induces an increase in
      5-HT release in widespread areas of the forebrain. This appears to be due to an
      effect on 5-HT cell bodies and not on 5-HT nerve endings in projection sites.

PMID- 7518504
TI  - A monoclonal antibody (IN-1) which neutralizes neurite growth inhibitory proteins
      in the rat CNS recognizes antigens localized in CNS myelin.
AB  - In previous studies two neurite growth inhibiting protein fractions of 35 and 250
      kDa were identified in myelin preparations of the rat CNS. These activities were
      not found in the myelin of PNS. A monoclonal antibody (mAb IN-1) was raised
      against the 250 kDa protein fraction and selected for its ability to neutralize
      the inhibitory effect of CNS myelin and of both isolated protein fractions. IN-1
      has been shown both in vitro and in vivo to neutralize the inhibitory effect of
      differentiated oligodendrocytes and CNS white matter. In the present study, the
      antigens of IN-1 were localized by immunohistochemistry on cryostat sections of
      the adult rat nervous system. The staining pattern of IN-1 was compared to that
      of mAbs specific for proteins found in CNS and PNS myelin. These proteins include
      myelin basic protein, myelin oligodendrocyte glycoprotein, and myelin associated
      glycoprotein. IN-1 stained white matter and myelinated fibre tracts in the CNS on
      sections of fresh frozen tissue fixed with 95% ethanol: 5% acetic acid (Clark's
      solution). Sciatic nerve myelin and spinal roots remained unstained. The staining
      pattern of IN-1 corresponded most closely to that of a mAb against myelin
      oligodendrocyte glycoprotein, a protein which occurs exclusively in CNS myelin
      and on differentiated oligodendrocytes.

PMID- 7518501
TI  - Dopamine-releasing action of 6R-L-erythro-tetrahydrobiopterin: analysis of its
      action site using sepiapterin.
AB  - Recently, we reported that 6R-L-erythro-tetrahydrobiopterin (6R-BH4), a natural
      cofactor for hydroxylases of tyrosine and tryptophan, has a monoamine-releasing
      action independent of its cofactor activity. Here we attempted to determine
      whether 6R-BH4 acts inside the cell or from the outside of the cell by using
      brain microdialysis in the rat striatum. For this purpose, sepiapterin, and
      immediate precursor of 6R-BH4 in the salvage pathway, was used to selectively
      increase the intracellular 6R-BH4 levels. Dialytic perfusion of sepiapterin
      increased tissue levels of reduced biopterin (mainly 6R-BH4) but not the
      extracellular levels. Administration of sepiapterin increased the extracellular
      levels of 3,4-dihydroxyphenylalanine (DOPA) (an index of in vivo tyrosine
      hydroxylase activity) and of dopamine (DA) (an index of in vivo DA release).
      Either of the increases was eliminated after pretreatment with a tyrosine
      hydroxylase inhibitor alpha-methyl-p-tyrosine. Administration of 6R-BH4 increased
      extracellular levels of reduced biopterin. DOPA, and DA. After pretreatment with
      alpha-methyl-p-tyrosine, the increase in DOPA levels was abolished, but most of
      the increase in DA levels persisted. The increase in DA levels also persisted
      after pretreatment with nitric oxide synthase inhibitors. These data demonstrate
      that 6R-BH4 stimulates DA release directly, independent of its cofactor action
      for tyrosine hydroxylase and nitric oxide synthase, by acting from the outside of
      neurons.

PMID- 7518505
TI  - Developmental expression of P0 mRNA and P0 protein in the sciatic nerve and the
      spinal nerve roots of the rat.
AB  - Expression of myelin P0 protein by myelinating Schwann cells in vivo is dependent
      on axonal influences. This report describes P0 gene expression during development
      of rat sciatic nerve and spinal nerve roots using Northern blotting, in situ
      hybridization and immunohistochemistry. We demonstrate that: (1) the appearance
      of P0 mRNA and P0 protein in Schwann cells during nerve development in the rat
      begins prenatally, at day 18 post-fertilization (E18); (2) P0 mRNA and P0 protein
      have essentially identical developmental profiles, and are expressed in Schwann
      cells that are many days prior to myelin formation; (3) initial P0 gene
      expression is greatest in Schwann cells at the periphery of nerve bundles and in
      Schwann cells in contact with motor axons; (4) the decline in P0 expression with
      nerve maturation is accompanied by a sharp decline in P0 message levels in most
      Schwann cells, but a small subpopulation of these cells continue to synthesize
      very high levels of P0 mRNA. This study provides data on myelin P0 protein gene
      expression and distribution during PNS development and adds further insights into
      the axonal influences controlling Schwann cell behaviour during myelination of
      the rat PNS.

PMID- 7518506
TI  - The Chinese palliative patient and family in North America: a cultural
      perspective.
AB  - Professionals may become frustrated when caring for the Chinese palliative
      patient and family, as we may expect them to behave or act like us. This paper
      discusses two distinctive characteristics which may be unfamiliar to Western
      caregivers. The first pertains to the concept of family-based popular health
      care, where the family assumes the major role of decision-maker on behalf of the
      patient. The second relates to the Eastern belief of silence surrounding the
      discussion of dying and the impending death, versus our Western orientation,
      which advocates openness and honesty. By gaining a greater understanding of these
      cultural traditions and practices, we can deliver more culturally sensitive
      health care to the Chinese patient and family.

PMID- 7518507
TI  - Family functioning and its implications for palliative care.
AB  - Palliative care programs are based on the principle that care should be directed
      to the family as a unit. However, existing guidelines for care of the family tend
      to be described in general terms. Analysis of data from a series of three
      research studies describing the experience of twenty-three families caring for a
      terminally ill member revealed that family functioning influenced their
      experience. The dimensions of family functioning are described and guidelines for
      working with families are proposed.

PMID- 7518508
TI  - Against entropy in palliative care.

PMID- 7518509
TI  - Palliative care--a passing fad? Understanding and responding to the signs of the
      times.

PMID- 7518510
TI  - Palliative medicine: a UK specialty.

PMID- 7518513
TI  - Modulation of the acetylcholine- and substance P-induced pulmonary edema by
      calcitonin gene-related peptide in the rabbit.
AB  - The effects of calcitonin gene-related peptide (CGRP) (6 x 10(-8) M) on
      hemodynamics and on pulmonary microvascular permeability were investigated in
      isolated, perfused rabbit lungs by measuring the arterial, capillary and venous
      pressures and the capillary filtration coefficient (Kf,c). CGRP was administered
      alone or in combination with capsaicin (10(-4) M), acetylcholine (ACh) (10(-11) M
      to 10(-7) M), substance P (SP) (10(-10) M to 10(-6) M) and serotonin (10(-4) M).
      The influence of a specific antagonist of CGRP receptors, CGRP8-37 (10(-8) M), on
      the pulmonary edema induced by these mediators was also considered. CGRP had no
      direct effect on the vascular pressures or on Kf,c. Capsaicin and serotonin
      induced an increase in Kf,c of 271 +/- 49% and 676 +/- 147% of base line,
      respectively. ACh and SP also increased the microvascular permeability, in
      proportion to the concentration. The effects of capsaicin, ACh and SP have been
      related to the activation of neurokinin NK1 receptors. Co-administration of CGRP
      with capsaicin and ACh enhanced the increase in Kf,c induced by these two drugs.
      By contrast, when co-injected with SP, CGRP inhibited the Kf,c increase induced
      by 10(-8) M and 10(-7) M of SP (P < .05) and significantly decreased the arterial
      and capillary pressures. CGRP also partly prevented the pulmonary edema induced
      by serotonin (P < .05). Pretreatment with CGRP8-37 partly prevented the effects
      of capsaicin and ACh on Kf,c but bestowed no protection against SP-induced
      pulmonary edema. These data suggest that CGRP is co-released with SP from the C
      fibers upon the action of capsaicin and ACh in the rabbit lung. Because CGRP
      potentiated the pulmonary edema induced in capsaicin and ACh, but decreased the
      effects of SP, we hypothesize that CGRP exerts a positive retro-control on the
      release of neuropeptides by these fibers but can attenuate their effects on the
      target cells.

PMID- 7518511
TI  - Characterization of platelet activity in neuroblastoma.
AB  - A study was conducted to characterize the platelet aggregation induced by
      neuroblastoma tissue to investigate the mechanism of hypercoagulability in
      patients with neuroblastoma. The patients whose tumor tissues were examined had
      been shown clinically to have enhanced platelet activity. Platelet aggregation
      induced by neuroblastoma tissue extract was compared with that of other pediatric
      tumors. The effects of pretreatment with an antithrombin agent and prostacyclin
      (PGI2) on the platelet aggregation induced by tumor tissue extracts were also
      evaluated. Tissue extracts of 12 of 15 neuroblastomas, 3 of 3 Wilms' tumors, and
      1 pheochromocytoma were demonstrated to have an activity that potentiated
      platelet aggregation in vitro. The platelet aggregation induced by tissue
      extracts of neuroblastomas and other tumor tissues was suppressed almost
      completely by pretreatment with a PGI2 analogue. The aggregation induced by
      neuroblastomas and the pheochromocytoma was also suppressed by pretreatment with
      an antithrombin agent, argatroban, whereas the aggregation induced by Wilms'
      tumors was not suppressed by this agent. These results suggest that (1) malignant
      tumors in children also have some chemical substances that sensitize platelet
      activity, such as those in adult cancers, and (2) thrombin is one of the
      mediators stimulating platelet aggregation in cases of neuroblastoma, although it
      is unlikely to be a contributing factor in other pediatric malignancies such as
      Wilms' tumor.

PMID- 7518512
TI  - Repeated inhibition of cholinesterase by chlorpyrifos in rats: behavioral,
      neurochemical and pharmacological indices of tolerance.
AB  - Previous work from this laboratory showed that daily s.c. injections of the
      organophosphate diisopropylfluorophosphate caused prolonged inhibition of
      cholinesterase (ChE) activity in whole blood and brain and downregulation of
      muscarinic receptors in the central nervous system; these changes were
      accompanied by progressive, persistent deterioration of working memory and motor
      function. Further, a single s.c. injection of the organophosphate insecticide
      chlorpyrifos (O,O',-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothionate, CPF),
      caused neurochemical changes of the same magnitude and duration, but transient
      impairment of working memory and motor slowing. In the present study, weekly
      injections of CPF (0, 15, 30 or 60 mg/kg s.c.) inhibited ChE activity in whole
      blood of rats by 60% to 90% after 5 weeks; the highest dose also induced tremor,
      working memory impairment and motor slowing in daily delayed matching-to
      position/visual discrimination tests. Reducing the CPF injection frequency to
      every other week relieved the inhibition of whole blood ChE activity (to 50%-75%
      of control) and ameliorated all the behavioral deficits. Reinstatement of weekly
      CPF injections (0, 15, 30, or 45 mg/kg) for 10 weeks inhibited whole blood ChE
      activity by 75% to 90%. Tremor was not observed during this period; however,
      motor slowing and working memory impairment persisted throughout the dosing
      period in all treated groups. Pharmacological evidence for tolerance to the
      muscarinic effects of CPF was observed on trial completion in the daily delayed
      matching-to-position/visual discrimination task: CPF-treated rats were
      supersensitive to scopolamine and subsensitive to pilocarpine. Nicotine reversed
      the reduction in trial completion associated with CPF. Changes in sensitivity to
      mecamylamine, d-amphetamine and haloperidol were not observed. Taken together,
      these studies indicate that inhibition of ChE activity by repeated injection of
      CPF produces a constellation of behavioral effects not evident after a single CPF
      treatment, even though both treatment regimens caused prolonged inhibition of ChE
      activity and downregulation of central muscarinic receptors.

PMID- 7518514
TI  - (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic
      ligand with cognition-enhancing and anxiolytic activities: I. In vitro
      characterization.
AB  - A diversity of nicotinic acetylcholine receptor (nAChR) subtypes has been
      identified in mammalian brain using recombinant DNA technology. Alterations in
      the activity of these acetylcholinegated ion channels have been implicated in a
      number of central nervous system disorders including Alzheimer's disease (AD).
      The potential therapeutic usefulness of (-)-nicotine [(S)-3-(1-methyl-2
      pyrrolidinyl) pyridine], the prototypic agonist at nAChRs, is severely limited by
      side effects that are the result of activation of both cholinergic and
      noncholinergic pathways in the central and peripheral nervous systems. This study
      sought to determine the in vitro selectivity of (S)-3-methyl-5-(1methyl-2
      pyrrolidinyl)isoxazole (ABT 418), a novel analog of (-)-nicotine in which the
      pyridine ring was replaced with an isoxazole bioisotere, to activate nAChRs. ABT
      418 was a potent inhibitor of [3H]-cytisine binding to nAChR in rat brain (Ki = 3
      nM) but was inactive (Ki > 10,000 nM) in 37 other receptor/neurotransmitter
      uptake/enzyme/transduction system binding assays, including those for alpha
      bungarotoxin, muscarinic and 5-hydroxytryptamine3 receptors. In PC12 cells, patch
      clamp studies indicated that ABT 418 was an agonist with an EC50 value of 209
      microM, a potency to activate cholinergic channel currents some 4-fold less than
      that of (-)-nicotine (52 microM). Channel current responses elicited by ABT 418
      were prevented by the cholinergic channel blocker, mecamylamine. ABT 418 was also
      approximately 10-fold less potent (EC50 value = 380 nM) than (-)-nicotine (40 nM)
      in increasing [3H]-dopamine release from rat striatal slices, an effect that was
      blocked by the nAChR antagonist, dihydro-beta-erythroidine (10 microM).2+ In
      contrast, ABT 418 appeared equipotent with (-)-nicotine in enhancing 86Rb+ flux
      from mouse thalamic synaptosomes. ABT 418 demonstrated an in vitro
      pharmacological profile of cholinergic channel activation that was robust at some
      nAChR, but not others. The reasons for this are unclear. However, a nAChR subtype
      selectivity may account for the in vitro potency differences of ABT 418 on
      various neurotransmitter systems, and the substantial separation between the
      cognitive enhancement/anxiolytic benefits, and the reduced central nervous system
      side-effect liabilities seen in vivo. ABT 418 represents the first neuronal nAChR
      ligand that differentiates the toxicities/liabilities and other negative aspects
      normally associated with liabilities and other negative aspects normally
      associated with (-)-nicotine from the potential pharmacological benefits of
      selective cholinergic channel activation.

PMID- 7518515
TI  - Endothelins stimulate cyclic AMP accumulation in the isolated rat anterior
      pituitary gland: possible involvement of ETA receptor activation and
      prostaglandin E2 production.
AB  - Effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on cyclic AMP (cAMP)
      levels were studied in the isolated rat anterior and intermediate-posterior
      pituitary slices. In the anterior pituitary, ET-1 increased cAMP levels in a
      concentration-dependent manner (10(-7)-10(-5) M). ET-3 also increased the levels
      at the same concentration range, but ET-1 was more potent than ET-3 at an
      approximate ED50, 10(-6) M. The stimulatory effects of ET-1 and ET-3 (10(-6) M)
      on cAMP levels were antagonized by the ETA receptor antagonist BQ 123, 2 x 10(-6)
      M, and the ETB receptor agonist IRL 1620 evoked only a weak increase in cAMP
      levels. Moreover, the effects of ET-1 and ET-3 were completely abolished by the
      cyclooxygenase inhibitor indomethacin, 2 x 10(-5) M. On the other hand, among
      prostaglandins, prostaglandin E2 (PGE2) increased cAMP levels in a concentration
      dependent manner (10(-7)-10(-5) M), whereas prostaglandin D2 and prostaglandin I2
      did not exhibit such effects. PGE2 levels were increased by application of ET-1
      (10(-8)-10(-5) M). The ET-1-induced PGE2 accumulation was strongly inhibited by
      indomethacin and BQ 123, but not by treatment with pertussis toxin (100 ng/ml, 6
      hr). Treatment with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine
      also elevated the cAMP level by approximately 9-fold above the basal cAMP level.
      After 3-isobutyl-1-methylxanthine, ET-1 failed to increase PGE2 and cAMP levels.
      In the intermediate-posterior pituitary, ET-1 and ET-3 did not affect cAMP
      levels. The results suggest that endothelins increase cAMP levels via ETA
      receptor activation interacting with the pertussis toxin-insensitive G-protein,
      in which PGE2 production is involved in the rat anterior pituitary, whereas
      endothelins lack these effects in the intermediate-posterior pituitary.

PMID- 7518516
TI  - Brain metastases of gestational trophoblastic tumor.
AB  - Brain involvement by gestational trophoblastic tumor (GTT) was diagnosed by
      computed tomography in 23 (17%) of 131 patients with metastatic GTT at King
      Faisal Specialist Hospital and Research Centre between January 1980 and December
      1990. All 23 patients had concurrent lung involvement, and 20 presented with
      neurologic symptoms. There were three treatment groups: Group A--methotrexate,
      actinomycin-D, chlorambucil and brain irradiation; group B--cisplatin, VP-16,
      actinomycin-D and intrathecal methotrexate; and group C--palliative therapy and
      other chemotherapy. While no patients in groups A or C survived, 4 (57%) of 7
      patients in group B achieved complete, sustained remission. Serum:cerebrospinal
      fluid beta-human chorionic gonadotropin ratios were measured in 9 patients and
      were < 60 in only 4 patients. The clinical features of patients with brain
      metastases are reviewed in detail.

PMID- 7518517
TI  - Development of single-agent chemotherapy regimens for gestational trophoblastic
      disease.
AB  - Single-agent chemotherapy for nonmetastatic gestational trophoblastic disease is
      most successful for patients who have had an antecedent molar pregnancy with a
      plateau or persistent beta-human chorionic gonadotropin elevation after molar
      evacuation. Traditionally, single-agent, five-day, intramuscular methotrexate has
      been associated with high cure rates, as has methotrexate with citrovorum factor
      rescue, which reduces toxicity. Standard definitions of low-risk gestational
      trophoblastic disease and response assessment are critical to a comparison of
      prognostic features related to single-agent therapy success. Methotrexate with
      folinic acid rescue administered as primary therapy does achieve an excellent
      therapeutic outcome with limited chemotherapy exposure but at increased cost. The
      weekly intramuscular methotrexate Gynecologic Oncology Group (GOG) regimen is
      inexpensive and allows close monitoring of disease status. Single-dose or pulsed
      actinomycin-D provides a high level of complete response, although
      gastrointestinal toxicity, mainly nausea and vomiting, is quite common.
      Management of first-line chemotherapy failures is unclear, although in the GOG
      methotrexate trial it was evident that another agent, such as actinomycin-D,
      should be used to provide the highest success rate. The use of a single agent in
      low-risk metastatic trophoblastic disease (lung and/or vaginal metastases)
      depends upon restricting it to patients who have not failed prior chemotherapy,
      have a low World Health Organization score and have no evidence of the presence
      of choriocarcinoma, but a much higher first-line failure rate should be
      anticipated than in nonmetastatic disease. Other single-agent regimens have been
      proposed that are worthy of investigation to create a safer, more efficacious and
      more convenient regimen for low-risk gestational trophoblastic disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7518518
TI  - High-risk metastatic gestational trophoblastic tumors. Current management.
AB  - Aggressive multimodality therapy with an appropriate combination of chemotherapy
      and adjuvant radiotherapy and surgery has resulted in a cure for most patients
      with high-risk, metastatic gestational trophoblastic tumors. The EMA-CO
      chemotherapy regimen, employing etoposide, high-dose methotrexate, actinomycin D,
      cyclophosphamide and vincristine, is highly effective and well tolerated.
      Complete response rates of 80-94% and survival rates of 82-100% have been
      reported. For patients with central nervous system metastases, whole brain
      irradiation is given simultaneously with the initiation of combination
      chemotherapy employing a high-dose methotrexate infusion. Surgical procedures,
      especially hysterectomy and thoracotomy, may be useful for the purpose of
      removing known foci of chemotherapy-resistant disease. Subsequent salvage
      chemotherapy with cisplatin and bleomycin in combination with etoposide will
      result in a cure for almost all patients. The factors that are most important in
      determining response to treatment in patients with metastatic, high-risk disease
      are metastases to sites other than the lung and vagina, more than eight
      metastases, previous failed chemotherapy and a World Health Organization score >
      or = 8.

PMID- 7518519
TI  - Administration of an anti-CD5 immunoconjugate to patients with rheumatoid
      arthritis: effect on peripheral blood mononuclear cells and in vitro immune
      function.
AB  - OBJECTIVE: An immunoconjugate, CD5 Plus, composed of ricin A chain and murine
      IgG1 anti-CD5 monoclonal antibody is under investigation for treatment of
      rheumatoid arthritis. To understand better the mechanism of action of this agent,
      alterations in immune function and lymphocyte subpopulations were assessed in a
      subset of patients consecutively enrolled in 2-phase II clinical trials. METHODS:
      Flow cytometric and in vitro functional analyses of peripheral blood mononuclear
      cells from 12 patients receiving 5 daily intravenous infusions of CD5 Plus at
      doses of 0.20 or 0.33 mg/kg were performed before, during and after treatment.
      RESULTS: Peripheral CD3+ T cells were significantly depleted (p < 0.01) during
      treatment on Days 2 and 5 and returned towards baseline on Days 15 to 29; changes
      in CD5+ B cells occurred in parallel. There was no significant treatment effect
      on monocytes. All T cell subsets examined, including CD4, CD8, CD45RA, CD45RO,
      HLA-DR+, TCR-alpha beta and TCR-gamma delta, were affected equally through Day
      15. On Day 29, the median CD4:CD8 ratio, elevated before treatment, was
      significantly decreased (p < 0.01), approaching the ratio observed in healthy
      controls. Proliferative responses to antigenic, allogeneic and mitogenic stimuli
      in vitro were depressed but detectable during the time of maximal T cell
      depletion and normalized to baseline values with recovery of T cell number.
      Spontaneous and pokeweed mitogen induced immunoglobulin secretion were unaffected
      in these patients. CONCLUSION: Treatment associated effects of CD5 Plus were
      observed for both T and B cell populations which bear the CD5 antigen, and were
      reversible, as measured by in vitro assays of immune cell function, phenotype and
      number.

PMID- 7518520
TI  - Soluble E-selectin is increased in inflammatory synovial fluid.
AB  - OBJECTIVE: To investigate the hypothesis that soluble E-selectin (sE-selectin)
      may be detected in synovial fluid (SF) and play a role in inflammatory arthritis.
      METHODS: We used a sandwich ELISA to measure sE-selectin in the SF of 58 patients
      with rheumatoid arthritis (RA), 9 with psoriatic arthritis (PsA), 30 with
      osteoarthritis (OA), 13 with gout, and 9 with calcium pyrophosphate dihydrate
      crystal deposition disease (CPPD). RESULTS: SF sE-selectin values in RA (mean
      1.49 ng/ml, 0.18-3.90) and PsA (mean 1.36 ng/ml, 0.88-2.31) were significantly
      higher than those with OA (mean 0.83 ng/ml, 0.00-1.83), gout (mean 1.04 ng/ml,
      0.11-3.42), or CPPD (mean 0.80 ng/ml, 0.20-1.47). Elevated SF sE-selectin was
      associated with elevated serum sE-selectin, erythrocyte sedimentation rate, and
      SF white blood cell count. CONCLUSION: Our findings suggest that endothelial cell
      activation and E-selectin may contribute to the development of inflammatory
      processes.

PMID- 7518521
TI  - Tolerance to the HLA-B27 and Klebsiella pneumoniae crossreactive epitope in mice
      transgenic for HLA-B2705 and human beta 2-microglobulin.
AB  - OBJECTIVE: To determine whether immunization of HLA-B27 transgenic mice with a
      peptide containing the crossreactive QTDRED sequence found in B2705 and
      Klebsiella nitrogenase induces a detectable immune response. METHODS: Mice were
      immunized with a synthesized peptide corresponding to the 65-84 region of HLA
      B2705 in Freund's complete adjuvant (FCA). Mice were bled for antibody assays 10
      days after the last injection. Popliteal lymph node cells for T cell
      proliferation assays were obtained 10 days after foot pad inoculation. RESULTS:
      The healthy control mice responded well to the peptide in both humoral and
      cellular assays. The transgenic mice carrying HLA-B2705 did not, although they
      did respond as expected to the FCA. CONCLUSION: Our data suggest that the
      homologous epitopes present in HLA-B2705 and Klebsiella do not induce a
      crossreactive immune response in animals naturally tolerant to the HLA antigen.

PMID- 7518522
TI  - Comparison of the conformation of active and nonactive backbone cyclic analogs of
      substance P as a tool to elucidate features of the bioactive conformation: NMR
      and molecular dynamics in DMSO and water.
AB  - The conformations of two backbone-cyclized substance P analogs as derived from 1H
      NMR and molecular dynamics simulations carried out in DMSO and water are
      described. The method of floating chiralities is used in the simulations to
      facilitate the diastereotopic assignment of methylene protons. One of the
      analogs, cyclo-[-(CH2)3-NH-CO-(CH2)4-Arg-Phe-Phe-N-]-CH2-CO-Leu-Met-NH2, is a
      highly active, selective agonist for the NK-receptor, while the other, cyclo[
      (CH2)2-NH-CO-(CH2)2-Gly-Arg-Phe-Phe-N-]-CH2-CO-Leu-Met-NH2, is inactive. Both
      analogs contain cyclic ring systems of the same size, varying in only the number
      of amide linkages. From the conformational analysis, the lack of activity can be
      attributed to the introduction of too much constraint into the ring system. This
      has an effect on the topological array of the important residues Arg-Phe-Phe. The
      results presented here are compared with biologically active analogs previously
      examined. The differences between conformations of active and inactive compounds
      are used to develop insight into the conformational requirements for biological
      activity.

PMID- 7518523
TI  - Identification of tricyclic analogs related to ellagic acid as potent/selective
      tyrosine protein kinase inhibitors.
AB  - The plant-derived natural product ellagic acid (1) has recently been identified
      as a potent, though nonselective, inhibitor of the tyrosine-specific protein
      kinase pp60src. This report details efforts directed toward the identification of
      tricyclic structures related to ellagic acid, with enhanced specificity for
      inhibition of pp60src over other protein kinases. Phenanthridinone and carbazole
      core structures were selected for investigation, since N-functionalization allows
      for the synthesis of numerous analogs which can be utilized to probe enzyme
      inhibitor interactions. These ring systems were prepared via a general sequence
      of biaryl bond formation followed by cyclization to form the desired tricyclic
      ring systems. N-Alkylation, -acylation, or -sulfonylation and deprotection with
      boron tribromide afford the target tetraphenolic phenanthridinones 5 and
      carbazoles 9. Several analogs from both of these series have potencies comparable
      to that of 1 and exhibit substantially enhanced selectivities for inhibition of
      pp60src relative to protein kinase A (PKA), a serine/threonine protein kinase.
      Carbazole-based analogs 9j,m,p are submicromolar inhibitors of pp60src, with
      potency for the target tyrosine kinase comparable to that of ellagic acid (1),
      however with 2 orders of magnitude greater selectivity versus that for PKA. As
      seen for ellagic acid, members of the phenanthridinone-based series (e.g., 5a)
      exhibited inhibition of pp60src in a manner which is partial mixed noncompetitive
      with respect to ATP, while analogs in the carbazole series (e.g., 9a) inhibit
      pp60src in an ATP competitive manner.

PMID- 7518524
TI  - A quantitative model of the Escherichia coli 16 S RNA in the 30 S ribosomal
      subunit.
AB  - We use a computer-based protocol for automated structure refinement of large RNAs
      and ribonucleoproteins to propose a three-dimensional model for the Escherichia
      coli 16 S RNA in the 30 S ribosomal subunit along with the first quantitative
      estimates of the uncertainties in the model. Our models are based on the 16 S RNA
      secondary structure, the small angle neutron scatter map of 30 S proteins,
      tertiary RNA-RNA and RNA-protein contacts as suggested by cross-linking, chemical
      footprinting and other experimental studies, and electron microscopy data for the
      shape of the 30 S subunit and placement of 16 S RNA fragments, along with known
      motifs in RNA structure. In addition, some data on the interaction of the
      tRNAs/mRNA with the 16 S RNA were used to localize the active site. Since there
      are not enough structural data to derive a unique three-dimensional folding of
      the 16 S RNA, several different conformations can be generated to satisfy the
      experimental data. A set of seven models was refined to survey the range of
      acceptable conformations. These models were analyzed to deduce probable positions
      and orientations of the different helical segments that comprise the 16 S RNA in
      the Escherichia coli small subunit, and one consensus model from this set is
      presented here. An estimate of the reliability of our predicted structure is made
      using the variations between the models, and about 75% of 16 S RNA helical
      segments are localized to 15 A or less in their position in the small subunit.
      Our models show a distinct separation of the three major domains of the 16 S RNA.
      The 5' major domain and the central domain are clustered in the body of the 30 S
      subunit, whereas the 3' major domain is localized in the head of the subunit. Our
      modeling results are compared with models of the 16 S RNA proposed by other
      researchers, and are seen to be similar to the manually built models by Stern et
      al. and Brimacombe et al. with a few significant differences. The position of
      nucleotides implicated by footprinting and crosslinking data in tRNA and mRNA
      binding, and in subunit association are examined, and many of these sites are
      seen to lie along the 30 S subunit neck, cleft and the platform.

PMID- 7518525
TI  - Strand displacement synthesis capability of Moloney murine leukemia virus reverse
      transcriptase.
AB  - The accepted model of retroviral reverse transcription includes a circular DNA
      intermediate which requires strand displacement synthesis for linearization and
      creation of an integration-competent, long terminal repeat-flanked DNA product.
      We have used an in vitro model of this last step of reverse transcription to
      examine the role of the viral enzyme, reverse transcriptase (RT), in displacement
      synthesis. We show that Moloney murine leukemia virus RT possesses an activity
      which allows for displacement synthesis through a minimum of 1,334 bp of duplex
      DNA--an extent much greater than that required during in vivo reverse
      transcription and over 25-fold greater than has been previously demonstrated for
      a viral RT. RT does not function as a helicase in the classical sense but appears
      to closely couple duplex DNA melting with synthesis-driven translocation of the
      enzyme. In the absence of synthesis, the unwound region created by a primer
      positioned RT appears to be no greater than 2 bp and does not advance along the
      template. Additionally, RT does not utilize ATP or any deoxynucleoside
      triphosphate not directly encoded by the template strand to catalyze processive
      duplex unwinding at a nick; nor does binding of the enzyme unwind duplex DNA in
      the absence of a 3' terminus. The approximate maximum chain elongation rate
      during strand displacement synthesis by Moloney murine leukemia virus RT falls
      between 0.73 and 1.5 nucleotides per s at 37 degrees C. The RNase H activity of
      RT does not appear to play a role in displacement synthesis; however, a 181-amino
      acid C-terminal truncation of RT displays a dramatically reduced ability to
      catalyze synthesis through duplex DNA.

PMID- 7518526
TI  - Genetic drift in hypervariable region 1 of the viral genome in persistent
      hepatitis C virus infection.
AB  - The hypervariable region 1 (HVR1) of the putative second envelope glycoprotein
      (gp70) of hepatitis C virus (HCV) contains a sequence-specific immunological B
      cell epitope that induces the production of antibodies restricted to the specific
      viral isolate, and anti-HVR1 antibodies are involved in the genetic drift of HVR1
      driven by immunoselection (N. Kato, H. Sekiya, Y. Ootsuyama, T. Nakazawa, M.
      Hijikata, S. Ohkoshi, and K. Shimotohno, J. Virol. 67:3923-3930, 1993). We
      further investigated the sequence variability of the HCV genomic region that
      entirely encodes the envelope proteins (gp35 and gp70); these sequences were
      derived from virus isolated during the acute and chronic phases of hepatitis in
      one patient, and we found that HVR1 was a major site for genetic mutations in HCV
      after the onset of hepatitis. We carried out epitope-mapping experiments using
      the HVR1 sequence derived from the acute phase of hepatitis and identified two
      overlapping epitopes which are each composed of 11 amino acids (positions 394 to
      404 and 397 to 407). The presence of two epitopes within HVR1 suggested that
      epitope shift happened during the course of hepatitis. Four of six amino acid
      substitutions detected in HVR1 were located within the two epitopes. We further
      examined the reactivities of anti-HVR1 antibodies to the substituted amino acid
      sequences within the two epitopes. HVR1 variants in both epitopes within the HVR1
      escaped from anti-HVR1 antibodies that were preexisting in the patient's serum.

PMID- 7518527
TI  - Recognition properties of a panel of human recombinant Fab fragments to the CD4
      binding site of gp120 that show differing abilities to neutralize human
      immunodeficiency virus type 1.
AB  - Six recombinant human Fab fragments that were derived from the same human
      immunodeficiency virus type 1 (HIV-1)-infected individual and are directed
      against the CD4 binding site (CD4bs) of the gp120 envelope glycoprotein were
      studied. A range of neutralizing activity against the HIV-1 (HXBc2) isolate was
      observed, with Fab b12 exhibiting the greatest potency among the Fabs tested. The
      neutralizing potency of Fab b12 was better than that of monoclonal whole
      antibodies directed against the third variable (V3) region of gp120. To explore
      the basis for the efficient neutralizing activity of b12, the recognition of a
      panel of HIV-1 gp120 mutants by the six Fabs was studied. The patterns of
      sensitivity to particular gp120 amino acid changes were similar for all six Fabs
      to those seen for anti-CD4bs monoclonal antibodies derived from HIV-1-infected
      individuals by conventional means. In addition, recognition by Fab b12
      demonstrated an atypical sensitivity to changes in the V1 and V2 variable
      regions. Next, the binding of the Fabs to monomeric gp120 and to the envelope
      glycoprotein complex was examined. Neither the binding properties of the b12 Fab
      to monomeric gp120 nor the ability of the Fab to compete with soluble CD4 for
      monomeric gp120 binding appeared to account for the greater neutralizing potency.
      However, both quantitative and qualitative differences between the binding of b12
      and that of less potent Fabs to the cell surface envelope glycoprotein complex
      were observed. Relative to less potently neutralizing Fabs, Fab b12 exhibited a
      higher affinity for a subpopulation of cell surface envelope glycoproteins, the
      conformation of which was best approximated by the mature gp120 glycoprotein.
      Apparently, subtle differences in the gp120 epitope recognized allow some members
      of the group of anti-CD4bs antibodies to bind to the functionally relevant
      envelope glycoprotein complex and to neutralize virus more efficiently.

PMID- 7518528
TI  - Significance of the immune response to a major, conformational B-cell epitope on
      the hepatitis C virus NS3 region defined by a human monoclonal antibody.
AB  - The nonstructural protein NS3 of hepatitis C virus (HCV) possesses two enzymatic
      domains which are thought to be essential for the virus life cycle: an N-terminal
      serine-type proteinase, responsible for the processing of nonstructural
      polypeptides, and a C-terminal nucleoside triphosphatase/helicase, presumably
      involved in the unwinding of the viral genome. The human antibody response to NS3
      usually appears early in the course of HCV infection and is predominantly
      directed against the carboxyl-terminal portion; however, its fine specificity and
      clinical significance are largely unknown. We have generated a human monoclonal
      antibody (hMAb), designated CM3.B6, from a cloned B-cell line obtained from the
      peripheral blood of a patient with chronic HCV infection, which selectively
      recognized the purified NS3 protein expressed in bacteria or in eukaryotic cells
      transfected with full-length or NS3 cDNA. Fine-specificity studies revealed that
      CM3.B6 recognized a 92-amino-acid sequence (clone 8, amino acids 1363 to 1454)
      selected from an NS3 DNase fragment library but failed to bind to 12-mer peptides
      synthesized from the same region, suggesting recognition of a conformational B
      cell epitope. Experiments using deletion mutants of clone 8 and competitive
      inhibition studies using a panel of NS3 peptide-specific murine MAbs indicated
      that limited N-terminal and C-terminal deletions resulted in a significant
      reduction of hMAb binding to clone 8, thus identifying a minimal antibody binding
      domain within clone 8. Competition experiments showed that binding of CM3.B6 to
      the NS3 protein was efficiently inhibited by 39 of 44 (89%) sera from HCV
      infected patients, suggesting that the hMAb recognized an immunodominant epitope
      within the NS3 region. More importantly, recognition of the sequence defined by
      CM3.B6 appeared to accurately discriminate between viremic and nonviremic anti
      HCV positive sera, suggesting potentially relevant clinical applications in the
      diagnosis and treatment of HCV infection.

PMID- 7518531
TI  - European brown hare syndrome virus: relationship to rabbit hemorrhagic disease
      virus and other caliciviruses.
AB  - Monoclonal antibodies directed against the capsid protein of rabbit hemorrhagic
      disease virus (RHDV) were used to identify field cases of European brown hare
      syndrome (EBHS) and to distinguish between RHDV and the virus responsible for
      EBHS. Western blot (immunoblot) analysis of liver extract of an EBHS virus
      (EBHSV)-infected hare revealed a single major capsid protein species of
      approximately 60 kDa that shared epitopes with the capsid protein of RHDV. RNA
      isolated from the liver of an EBHSV-infected hare contained two viral RNA species
      of 7.5 and 2.2 kb that comigrated with the genomic and subgenomic RNAs of RHDV
      and were recognized by labeled RHDV cDNA in Northern (RNA) hybridizations. The
      nucleotide sequence of the 3' 2.8 kb of the EBHSV genome was determined from four
      overlapping cDNA clones. Sequence analysis revealed an open reading frame that
      contains part of the putative RNA polymerase gene and the complete capsid protein
      gene. This particular genome organization is shared by RHDV but not by other
      known caliciviruses. The deduced amino acid sequence of the capsid protein of
      EBHSV was compared with the capsid protein sequences of RDDV and other
      caliciviruses. The amino acid sequence comparisons revealed that EBHSV is closely
      related to RHDV and distantly related to other caliciviruses. On the basis of
      their genome organization, it is suggested that caliciviruses be divided into
      three groups.

PMID- 7518529
TI  - Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two
      distinct E2-specific products with different C termini.
AB  - The hepatitis C virus (HCV) H strain polyprotein is cleaved to produce at least
      nine distinct products: NH2-C-E1-E2-NS2-NS3-NS4A-NS4B-NS5A-NS5B-CO OH. In this
      report, a series of C-terminal truncations and fusion with a human c-myc epitope
      tag allowed identification of a tenth HCV-encoded cleavage product, p7, which is
      located between the E2 and NS2 proteins. As determined by N-terminal sequence
      analysis, p7 begins with position 747 of the HCV H strain polyprotein. p7 is
      preceded by a hydrophobic sequence at the C terminus of E2 which may direct its
      translocation into the endoplasmic reticulum, allowing cleavage at the E2/p7 site
      by host signal peptidase. This hypothesis is supported by the observation that
      cleavage at the E2/p7 and p7/NS2 sites in cell-free translation studies was
      dependent upon the addition of microsomal membranes. However, unlike typical
      cotranslational signal peptidase cleavages, pulse-chase experiments indicate that
      cleavage at the E2/p7 site is incomplete, leading to the production of two E2
      specific species, E2 and E2-p7. Possible roles of p7 and E2-p7 in the HCV life
      cycle are discussed.

PMID- 7518530
TI  - Different abilities of Friend murine leukemia virus (MuLV) and Moloney MuLV to
      induce promonocytic leukemia are due to determinants in both psi-gag-PR and env
      regions.
AB  - Moloney murine leukemia virus (M-MuLV) is capable of inducing promonocytic
      leukemia in 50% of adult BALB/c mice that have received peritoneal injections of
      pristane, but Friend MuLV strain 57 (F-MuLV) is nonleukemogenic under similar
      conditions. It was shown earlier that these differences could not be mapped to
      the U3 region of the virus long terminal repeat, indicating the probable
      influence of structural genes and/or R-U5 sequences. In this study, reciprocal
      chimeras containing exchanged structural genes and R-U5 sequences from these two
      closely related viruses were analyzed for differences in ability to induce
      disease. Results showed that two regions of F-MuLV, psi-gag-PR and env, when
      substituted for those of M-MuLV were dramatically disease attenuating. The 5'
      most region, which is widely distributed, overlaps with the 5' end of the env
      intron and includes the RNA packaging region, psi, the entire gag coding region,
      and the viral protease coding region (PR) of pol. It was also found that
      reciprocal constructs having substitutions of both of these regions of M-MuLV in
      an F-MuLV background allowed full reestablishment of promonocytic leukemia. These
      leukemias were positive for c-myb rearrangements which are characteristic of M
      MuLV-induced promonocytic leukemias. Neither region alone, however, was
      sufficient to produce disease with a greater incidence than 13%. Further studies
      demonstrated that the inability of viruses with psi, gag, PR, or env sequences
      from F-MuLV to induce leukemia in this model system was not due to their
      inability to replicate in hematopoietic tissue, to integrate into the c-myb locus
      early on after infection in vivo, or to express gag-myb mRNA characteristic of M
      MuLV-induced preleukemic cells and acute leukemia.

PMID- 7518532
TI  - Characterization of epitopes defining two major subclasses of polytropic murine
      leukemia viruses (MuLVs) which are differentially expressed in mice infected with
      different ecotropic MuLVs.
AB  - Polytropic murine leukemia viruses (MuLVs) arise in mice by recombination of
      ecotropic MuLVs with endogenous retroviral envelope genes and have been
      implicated in the induction of hematopoietic proliferative diseases. Inbred mouse
      strains contain many endogenous sequences which are homologous to the polytropic
      env genes; however, the extent to which particular sequences participate in the
      generation of the recombinants is unknown. Previous studies have established
      antigenic heterogeneity among the env genes of polytropic MuLVs, which may
      reflect recombination with distinct endogenous genes. In the present study, we
      have examined many polytropic MuLVs and found that nearly all isolates fall into
      two mutually exclusive antigenic subclasses on the basis of the ability of their
      SU proteins to react with one of two monoclonal antibodies, termed Hy 7 and MAb
      516. Epitope-mapping studies revealed that reactivity to the two antibodies is
      dependent on the identity of a single amino acid residue encoded in a variable
      region of the receptor-binding domain of the env gene. This indicated that the
      two antigenic subclasses of MuLVs arose by recombination with distinct sets of
      endogenous genes. Evaluation of polytropic MuLVs in mice revealed distinctly
      different ratios of the two subclasses after inoculation of different ecotropic
      MuLVs, suggesting that individual ecotropic MuLVs preferentially recombine with
      distinct sets of endogenous polytropic env genes.

PMID- 7518535
TI  - [Markers of inflammatory response and sizes of myocardial infarct].

PMID- 7518533
TI  - Phenotypic mixing between different hepadnavirus nucleocapsid proteins reveals C
      protein dimerization to be cis preferential.
AB  - Hepadnaviruses encode a single core (C) protein which assembles into a
      nucleocapsid containing the polymerase (P) protein and pregenomic RNA during
      viral replication in hepatocytes. We examined the ability of heterologous
      hepadnavirus C proteins to cross-oligomerize. Using a two-hybrid assay in HepG2
      cells, we observed cross-oligomerization among the core proteins from hepatitis B
      virus (HBV), woodchuck hepatitis virus, and ground squirrel hepatitis virus. When
      expressed in Xenopus oocytes, in which hepadnavirus C proteins form capsids, the
      C polypeptides from woodchuck hepatitis virus and ground squirrel hepatitis
      virus, but not duck hepatitis B virus, can efficiently coassemble with an epitope
      tagged HBV core polypeptide to form mixed capsids. However, when two different
      core mRNAs are coexpressed in oocytes the core monomers show a strong preference
      for forming homodimers rather than heterodimers. This holds true even for
      coexpression of two HBV C proteins differing only by an epitope tag, suggesting
      that core monomers are not free to diffuse and associate with other monomers.
      Thus, mixed capsids result from aggregation of different species of homodimers.

PMID- 7518534
TI  - Differential effects of flanking residues on presentation of epitopes from
      chimeric peptides.
AB  - Chimeric peptides in which the optimal H-2d mouse hepatitis virus nucleocapsid
      (pN) and human immunodeficiency virus type 1 (p18) epitopes, separated by 38, 7,
      or 2 amino acids, were expressed from a single open reading frame by using
      recombinant vaccinia viruses to analyze antigen processing of proximal class I
      restricted epitopes. Recognition of the carboxy-terminal Dd-restricted p18
      epitope was independent of the amino-terminal flanking residues. By contrast,
      proximity of the carboxy-terminal epitope decreased recognition of the amino
      terminal Ld-restricted pN epitope. Immunization resulted in the induction of both
      p18- and pN-specific antiviral cytotoxic T lymphocytes, irrespective of the
      number of amino acids separating the epitopes.

PMID- 7518538
TI  - Mechanism of the vascular action of parathyroid hypertensive factor.
AB  - The present studies investigated the effect of parathyroid hypertensive factor
      (PHF) on intracellular calcium regulation in VSMC. Nifedipine inhibited the
      hypertensive effect of PHF in Sprague-Dawley (SD) rats in vivo. PHF amplified the
      L-type calcium current in vascular smooth-muscle cells (VSMCs) isolated from SD
      rat tail artery. PHF potentiated the tension induced by norepinephrine (NE) in
      the presence of normal added CaCl2 and inhibited the tension dependent on Ca2+
      release from intracellular calcium store(s) induced by NE in SD rat tail artery
      helical strips. PHF potentiated the intracellular free calcium concentration
      ([Ca2+]i) increment induced by KCl in cultured VSMCs from SD rat tail artery. All
      of the in vitro cellular calcium effects of PHF temporally correlated with its
      delayed hypertensive effect in vivo. PHF did not affect the accumulation of
      inositol phosphates in SD rat tail artery. Infusion of theophylline blunted the
      hypertensive effect of PHF in SD rats, suggesting that PHF may stimulate
      phosphodiesterase (PDE) activity. We suggest that PHF may potentiate the effects
      of other vasoconstrictors on calcium channels and increase [Ca2+]i, which would
      then lead to an increase in the responsiveness of the VSMC to other
      vasoconstrictors, and therefore an increase in blood pressure. The action of PHF
      may involve stimulation of PDE activity.

PMID- 7518536
TI  - [Study of reperfusion arrhythmias in experimental models using the mapping
      method].

PMID- 7518537
TI  - Parathyroid Hypertensive Factor: A New Circulating Substance in Essential
      Hypertension. Proceedings of a satellite symposium to the 14th ISH meeting.
      Madrid, Spain, June 13, 1992.

PMID- 7518539
TI  - Serum-mediated intracellular calcium changes in normotensive and hypertensive red
      blood cells: role of parathyroid hypertensive factor.
AB  - To study cellular calcium metabolism in hypertension, we investigated the effects
      of human serum, and of the circulating pressor substance, parathyroid
      hypertensive factor (PHF), on the cytosolic free calcium (Cai-f) content of
      erythrocytes from normotensive and essential hypertensive subjects. In their own
      serum, basal Cai-f was higher in hypertensive than in normotensive and essential
      hypertensive subjects. In their own serum, basal Cai-f was higher in hypertensive
      than in normotensive subjects (mean +/- SEM; 39.4 +/- 4.0 vs. 23.4 +/- 2.7 nM; p
      < 0.05). Without serum, Cai-f was lower and not significantly different (23.0 +/-
      3.1 vs. 18.2 +/- 2.7 nM; p = not significant). Addition of serum to serum-free
      erythrocytes increased Cai-f, and reestablished the Cai-f gradient in
      hypertensive cells (31.4 +/- 0.8 vs 23.0 +/- 2.3 nM; p < 0.05). PHF levels were
      directly related to basal Cai-f (r = -0.648; p < 0.05) and to the serum-induced
      rise in Cai-f (r = 0.600; p < 0.05). Furthermore, semipurified PHF, but not
      similarly prepared normotensive serum, increased Cai-f in normal human
      erythrocytes (PHF: +83.9 +/- 37.3% vs. +14.5 +/- 27.5%; p < 0.05). We conclude
      that circulating factors in general, and PHF in particular, may account for the
      increased basal Cai-f of hypertension, and thus at least partially contribute to
      te pathophysiology of the hypertensive process.

PMID- 7518540
TI  - Parathyroid cross-transplantation and development of high blood pressure in rats.
AB  - To clarify further the relationships between parathyroid glands and the
      development of hypertension, we studied the effect of cross-transplantation of
      these glands from young hypertensive rats in normotensive recipients. The
      parathyroid glands were isolated in 5-week-old hypertensive rats of the Lyon
      (male and female) and Milan (only male) strains and immediately grafted into the
      corresponding, just parathyroidectomized normotensive rats of the same age.
      Control rats were either sham-operated or grafted with the glands of the same
      normotensive strain. Plasma calcium concentration immediately decreased after
      parathyroidectomy (PTX) and returned to near normal values 3 weeks after the
      graft. Systolic blood pressure increased slightly, but significantly, in
      normotensive animals grafted with hypertensive glands compared with that in
      normotensive control rats (mean increase, +9 mm Hg in males; +5 mm Hg in
      females). In conclusion, parathyroid gland transplantation from the hypertensive
      strain is able to chronically enhance blood pressure in the normotensive animal.
      The parathyroid hypertensive factor recently described may be implicated in these
      two hypertensive strains. Our data extend observations obtained previously in
      SHRs and stroke-prone SHRs and add further evidence for a major function of
      parathyroid glands in experimental hypertension.

PMID- 7518541
TI  - Clinical aspects of parathyroid hypertensive factor.
AB  - To determine the clinical significance of parathyroid hypertensive factor (PHF),
      physiological studies previously performed in animal models of hypertension were
      parallelled by human studies. These studies revealed that PHF-like activity is
      present in human hypertension, where it correlates with the salt-sensitive, low
      renin state. As in spontaneously hypertensive rats, both supplemental calcium and
      calcium-channel blockers appear to be useful in the treatment of PHF-related
      hypertension. In primary hyperparathyroid patients, PHF presence is linked with
      the presence of hypertension. Postparathyroidectomy blood pressure falls in
      parallel with PHF levels. These preliminary human studies suggest that PHF may be
      a useful marker in the treatment of hypertension.

PMID- 7518542
TI  - Dietary calcium supplementation prevents the development of hypertension in
      deoxycorticosterone-salt-treated dogs.
AB  - High levels of dietary calcium attenuate the elevation of arterial pressure
      induced by deoxycorticosterone (DOC)-salt in trained, conscious dogs. This
      response resulted primarily from the failure of the expected rise in peripheral
      vascular resistance to develop. In addition, the enhanced pressor sensitivity to
      norepinephrine and angiotensin II associated with DOC-salt hypertension was
      normalized by high levels of dietary calcium. These changes could not be
      explained by changes in serum potassium concentration, plasma catecholamines
      concentration, or plasma volume. A possible explanation is that high levels of
      dietary calcium inhibit a parathyroid hypertensive factor that has been observed
      to be elevated in mineralocorticoid-induced hypertension. This hypothesis
      requires further studies.

PMID- 7518543
TI  - Parathyroid hypertensive factor and non-insulin-dependent diabetes mellitus.
AB  - The recently discovered parathyroid hypertensive factor (PHF) has been shown to
      increase intracellular free calcium levels. High intracellular calcium can cause
      insulin resistance, as seen in non-insulin-dependent diabetes mellitus (NIDDM)
      patients. We therefore compared plasma PHF activity in NIDDM patients and
      nondiabetic control subjects using a rat bioassay. More NIDDM patients (65%) than
      non-diabetic controls (33.3%) had detectable PHF activity. When injected into
      rats, plasma of 185 NIDDM patients caused an average increase of 4.89 +/- 0.68 mm
      Hg in rat mean arterial pressure (MAP). This change was significantly greater
      than a slight drop of 0.42 +/- 0.96 mm Hg (mean +/- SE) for the 127 nondiabetic
      control subjects (Student's t test, p < 0.001). A higher percentage of the NIDDM
      patients than of the non-diabetic patients were hypertensive. However, a
      stratified analysis showed that diabetic patients consistently had significantly
      higher PHF levels than did nondiabetic patients, regardless of being hypertensive
      or not. PHF activity did not correlate with age, sex, body mass index, or the
      type of hypoglycemic agent taken. However, multivariate logistic regression
      analysis showed a positive correlation between cholesterol and PHF level among
      the diabetic patients (p = 0.03), but such a correlation did not exist among the
      non-diabetic controls. Our data indicate that elevated PHF may be responsible for
      insulin resistance in a fraction of NIDDM patients and suggest that PHF may be
      related to serum cholesterol levels in NIDDM.

PMID- 7518545
TI  - Cardiovascular effects of human parathyroid hormone and parathyroid hormone
      related peptide.
AB  - Parathyroid hormone (PTH) is hypotensive in mammals and is a potent coronary
      vasodilator. Parathyroid hormone-related peptide (PTHrp) has been reported to
      have similar vascular activity. In the present study, the effects of human PTH
      (hPTH) and human PTHrp (hPTHrp) were compared in various in vivo and in vitro
      assays. In vivo studies included blood pressure measurement and coronary blood
      flow determination with labeled microspheres in anesthetized and cannulated
      normotensive rats. Isolated rat tail artery and portal vein helical strips were
      used in studying tension development in vitro. In the blood pressure assay, PTHrp
      was several times more potent than PTH. PTHrp was also significantly more potent
      than PTH in relaxing tail artery precontracted with arginine vasopressin (AVP).
      PTHrp and PTH both inhibited the spontaneously contracting portal vein, but again
      PTHrp was significantly more potent. PTHrp (1 microgram/kg) produced a greater
      increase in coronary blood flow as compared with the same dose of PTH. These data
      suggest that PTHrp is more potent than PTH in its cardiovascular actions. It is
      possible that PTHrp is the endogenous vasodilating ligand, and the structural
      similarity between PTH and PTHrp may explain the pharmacological action of PTH.
      It is therefore unlikely that PTH or PTHrp may be involved in the genesis or
      maintenance of hypertension. Because the parathyroid gland seems to be involved
      in some forms of essential hypertension, factor(s) other than PTH or PTHrp may be
      responsible.

PMID- 7518546
TI  - Biochemical characteristics of a calmodulin-phosphodiesterase activator increased
      in spontaneously hypertensive mice and rats.
AB  - The biochemical characteristics of calmodulin-phosphodiesterase (CaM-PDE) are
      described. It is a cytosolic, hydrophobic, and heat-, acid-, and base-stable
      compound sensitive to proteases. It is optimally extracted from neutral
      supernatants by CHCl3/MeOH (2:1 or 1:1). It partitions into the organic fraction
      of CHCl3/MeOH extracts, whereas the aqueous fraction contains a component that
      potentiates the activator's capacity to stimulate CaM-PDE. The activator
      interacts with PDE by increasing its apparent affinity for CaM. Size partition
      chromatography of CHCl3/MeOH extracts from spontaneously hypertensive rats
      produces two activity peaks, one eluting at void volume with the second eluting
      at a position corresponding to a 4-kDa peptide. The compound at void volume can
      be converted to the 4-kDa entity by sonication. The CaM-PDE activator behaves as
      a lipopeptide that shares several characteristics with parathyroid hypertensive
      factor.

PMID- 7518548
TI  - Monitoring of treatment outcome in acute promyelocytic leukemia by RT-PCR.
AB  - A rearrangement between the PML and RAR-alpha genes underlies the acute
      promyelocytic leukemia (APL)-specific t(15;17) translocation, leading to the
      production of a chimeric mRNA. Recent development of a reverse-transcription
      polymerase chain reaction (RT-PCR) assay for the PML/RAR-alpha hybrid has proven
      useful for rapid diagnosis and monitoring of minimal residual disease (MRD) in
      APL patients. Preliminary studies in which the prognostic significance of RT-PCR
      was evaluated indicate that this test may identify patients at high risk of
      relapse.

PMID- 7518547
TI  - Purification and structural characterization of parathyroid hypertensive factor.
AB  - Parathyroid hypertensive factor (PHF) has been purified from two sources of
      material: plasma of spontaneously hypertensive rats (SHRs) and culture medium
      from organ culture of SHR parathyroid glands. Chromatographic characteristics of
      PHF from these two sources are identical. Biological activity of PHF (assayed as
      the characteristic delayed hypertensive response in normotensive rats) is
      sensitive to degradation by treatment in base, and the enzymes trypsin,
      chymotrypsin, phospholipase C, and phospholipase D. PHF activity may also be
      extracted from source material with chloroform: methanol (4:1). A hypothetical
      structure for the active component of PHF is suggested. This is comprised of a
      peptide liked to a lysophospholipid.

PMID- 7518544
TI  - Effects of weight reduction on circulating parathyroid hypertensive factor
      levels.
AB  - This study evaluated changes in parathyroid hypertensive factor (PHF) in 18 obese
      individuals. PHF levels were measured prior to the onset of a low calorie diet
      (800 kcal/day), and at 3-4 weeks, 7-8 weeks, and 11-12 weeks after initiation of
      the diet. Blood pressure, forearm vascular resistance, and platelet intracellular
      calcium ([Ca2+]i) levels were also measured at the same time. Although blood
      pressure, vascular resistance, and platelet [Ca2+]i decreased significantly in
      association with the low-calorie diet and weight reduction, PHF levels did not
      change significantly during the 12-week diet period. We conclude that PHF levels
      do not track with reductions in blood pressure, vascular resistance, and platelet
      [Ca2+]i levels in obese individuals.

PMID- 7518549
TI  - E2A/HLF fusion cDNAs and the use of RT-PCR for the detection of minimal residual
      disease in t(17;19)(q22;p13) acute lymphoblastic leukemia.
AB  - Three cases of acute lymphoblastic leukemia (ALL) with the rare t(17;19)(q22;p13)
      translocation were investigated for E2A/HLF fusion genes using reverse
      transcription coupled with polymerase chain reaction (RT-PCR). The patients had C
      ALL, F/17 years (case 1) or pre-B ALL, M/11 years (case 2) and M/13 years (case
      3). Case 1 had an event-free survival (EFS) of 42 months. Case 2 was ultimately
      refractory to treatment. Case 3 presented following EFS of 16 months in
      morphological remission (1% blasts), but with immunological and cytogenetic
      evidence of active disease, then relapsed, remitted and relapsed. Type II E2A/HLF
      fusion cDNA was found at diagnosis (cases 1, 2), at presentation (case 3) and in
      all samples tested, whether with active disease or in complete remission (CR).
      Case 3 showed, in addition, type I fusion E2A/HLF cDNA at presentation, through
      induction therapy when there was evidence of active disease, but not in CR. Cases
      1 and 3 had bone marrow transplantation while in CR but with residual disease
      detectable by RT-PCR. All patients have died of ALL. Two cases (2 and 3) had
      hypercalcemia with bone lesions. No case had any evidence of disseminated
      intravascular coagulation. This is the first demonstration of the value of RT-PCR
      for the detection of minimal residual disease in t(17;19) ALL.

PMID- 7518550
TI  - Localization of the human CD40 gene to chromosome 20, bands q12-q13.2.
AB  - CD40 is a surface glycoprotein, member of the nerve growth factor receptor
      family, which is expressed on B cells and plays an important role in their
      development, growth, and differentiation. Using chromosomal in situ
      hybridization, we localized the CD40 gene to the long arm of chromosome 20, bands
      q12-q13.2. This localization correlates well with the mapping of the murine CD40
      gene to the distal region of chromosome 2, syntenic to the human 20q11-q13
      region.

PMID- 7518551
TI  - Suppression of the development of murine myeloid leukemia with granulocyte colony
      stimulating factor by inducing apoptosis of leukemic cells.
AB  - We studied the antileukemic effect of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) by using a radiation-induced murine myeloid leukemia
      cell line C2M-A5. Intravenous inoculation of C2M-A5 cells into C3H/He mice
      resulted in the development of myeloid leukemia. However, the leukemic death of
      the mice was completely suppressed by the subcutaneous injections of rhG-CSF. In
      order to clarify the mechanism of the suppression, effects of rhG-CSF on C2M-A5
      cells were studied in vitro. While C2M-A5 cells grew exponentially in the absence
      of rhG-CSF, the viability, the growth, and the self-renewal capacity of C2M-A5
      cells were all suppressed in cultures in the presence of rhG-CSF. Preincubation
      with rhG-CSF for 48 h deprived C2M-A5 cells of the ability to induce leukemia in
      syngeneic mice. Morphological examination revealed the appearance of apoptotic
      changes of C2M-A5 cells in cultures containing rhG-CSF over the 2-day incubation
      period. In gel electrophoresis, the DNA from C2M-A5 cells incubated with rhG-CSF
      for 48 h showed a ladder of degradated DNA bands compatible with apoptosis. From
      these results, we concluded that the apoptosis of C2M-A5 cells played a key role
      in the antileukemic effect of rhG-CSF.

PMID- 7518552
TI  - Increase of erythropoiesis and thrombopoiesis, and induction of remission by
      granulocyte colony-stimulating factor (G-CSF) in a patient with hypoplastic
      leukemia.

PMID- 7518554
TI  - Palliative medicine education for medical students: a survey of British medical
      schools, 1992.
AB  - The new specialty of palliative medicine is now recognized as making a
      significant contribution, not only to the practice of cancer medicine, but also
      to the care of terminal disease. This article reports an enquiry into the current
      teaching of palliative medicine in undergraduate curricula in Britain. A
      questionnaire concerning palliative medicine teaching was sent in December 1992
      to undergraduate deans of all medical schools, colleges and faculties (hereafter
      referred to as schools). Replies were received from all and were analysed. Most
      of the subjects represented by palliative medicine were taught in all schools by
      palliative medicine specialists or in sessions of other specialisms, or both.
      Many schools gave opportunity for students to visit local palliative care units
      or hospices; a few required it as part of the syllabus. The amount of time
      devoted to this subject in the curricula varied considerably. Eleven per cent of
      schools regularly asked questions on palliative medicine in final examinations;
      half occasionally did so, but 30% reported that there was never a question on
      palliative medicine in finals. In the light of recent publications by the General
      Medical Council and the Standing Medical Advisory Committee and Standing Nursing
      and Midwifery Advisory Committee, I urge that increasing attention be paid to
      teaching the subjects represented by palliative medicine and to examining it. I
      suggest that the recently published core curriculum will enable this to be
      carried out more effectively.

PMID- 7518555
TI  - Benign prostatic hypertrophy. Options for management.

PMID- 7518556
TI  - The blip syndrome.

PMID- 7518553
TI  - Effects of space flight stress on proopiomelanocortin, proenkephalin A, and
      tachykinin neuropeptidergic systems in the rat posterior pituitary.
AB  - beta-endorphin-like immunoreactivity (BE-li), methionine enkephalin-like
      immunoreactivity (ME-li), and substance P-like immunoreactivity (SP-li) were
      measured in the posterior pituitary of rats that experienced a 5-day space flight
      in a Space Shuttle. ME-li and SP-li were both significantly lower compared to the
      control rats. However, there was no difference in BE-li between flight and
      control rats. These data suggest that the space flight stress diminished the
      methionine enkephalin (ME) and substance P (SP) concentrations in the posterior
      pituitary without affecting the beta-endorphin (BE) concentration. Thus, the
      proenkephalin A and tachykinin, but not proopiomelanocortin, neuropeptidergic
      systems in the posterior pituitary may respond to this type of unique stress.

PMID- 7518557
TI  - Causes for concern in the use of prostate-specific antigen assays.

PMID- 7518558
TI  - Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon
      RI cross-linking.
AB  - Tyrosine phosphorylation of several cellular proteins is one of the earliest
      signaling events induced by cross-linking of the high-affinity receptor for
      immunoglobulin E (Fc epsilon RI) on mast cells or basophils. Tyrosine kinases
      activated during this process include the Src family kinases, Lyn, c-Yes, and c
      Src, and members of another subfamily, Syk and PTK72 (identical or highly related
      to Syk). Recently, some of us described two novel tyrosine kinases, Emb and Emt,
      whose expression was limited to subsets of hematopoietic cells, including mast
      cells. Emb turned out to be identical to Btk, a gene product defective in human X
      linked agammaglobulinemia and in X-linked immunodeficient (xid) mice. Here we
      report that Fc epsilon RI cross-linking induced rapid phosphorylation on
      tyrosine, serine, and threonine residues and activation of Btk in mouse bone
      marrow-derived mast cells. A small fraction of Btk translocated from the cytosol
      to the membrane compartment following receptor cross-linking. Tyrosine
      phosphorylation of Btk was not induced by either a Ca2+ ionophore (A23187),
      phorbol 12-myristate 13-acetate, or a combination of the two reagents. Co
      immunoprecipitation between Btk and receptor subunit beta or gamma was not
      detected. The data collectively suggest that Btk is not associated with Fc
      epsilon but that its activation takes place prior to protein kinase C activation
      and plays a novel role in the Fc epsilon RI signaling pathway.

PMID- 7518559
TI  - Regulation by protein-tyrosine phosphatase PTP2 is distinct from that by PTP1
      during Dictyostelium growth and development.
AB  - We have cloned a gene encoding a second Dictyostelium discoideum protein-tyrosine
      phosphatase (PTP2) whose catalytic domain has approximately 30 to 39% amino acid
      identity with those of other PTPs and a 41% amino acid identity with D.
      discoideum PTP1. Like PTP1, PTP2 is a nonreceptor PTP with the catalytic domain
      located at the C terminus of the protein. PTP2 has a predicted molecular weight
      of 43,000 and possesses an acidic 58-amino-acid insertion 24 amino acids from the
      N terminus of the conserved catalytic domain. PTP2 transcripts are expressed at
      moderate levels in vegetative cells and are induced severalfold at the onset of
      development. Studies with a PTP2-lacZ reporter gene fusion indicate that PTP2,
      like PTP1, is preferentially expressed in prestalk and anterior-like cell types
      during the multicellular stages of development. PTP2 gene disruptants (ptp2 null
      cells) are not detectably altered in growth and show a temporal pattern of
      development similar to that of wild-type cells. ptp2 null slugs and fruiting
      bodies, however, are significantly larger than those of wild-type slugs,
      suggesting a role for PTP2 in regulating multicellular structures. D. discoideum
      strains overexpressing PTP2 from the PTP2 promoter exhibit growth rate and
      developmental abnormalities, the severity of which corresponds to the level of
      PTP2 overexpression. Strains with high overexpression of the PTP2 gene grow
      slowly on bacterial lawns and produce small cells in axenic medium. When
      development is initiated in these strains, cells are able to aggregate but then
      stop further morphogenesis for 6 to 8 h, after which time a variable fraction of
      these aggregates continue with normal timing, producing diminutive fruiting
      bodies. These disruption and overexpression phenotypes for PTP2 are distinct from
      the corresponding mutant PTP1 phenotypes. Immunoprobing PTP2 mutant strains
      during growth and development with antiphosphotyrosine antibodies reveals several
      changes in the tyrosine phosphorylation of proteins in PTP2 mutant strains
      compared with that in wild-type cells. These changes are different from those
      identified in the previously characterized corresponding PTP1 disruption and
      overexpression mutant strains. Thus, although PTP2 and PTP1 are nonreceptor PTPs
      with similar spatial patterns of expression, our findings suggest that they
      possess distinct regulatory functions in controlling D. discoideum growth and
      development.

PMID- 7518560
TI  - Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor
      receptor.
AB  - We analyzed the binding site(s) for Grb2 on the epidermal growth factor (EGF)
      receptor (EGFR), using cell lines overexpressing EGFRs containing various point
      and deletion mutations in the carboxy-terminal tail. Results of co
      immunoprecipitation experiments suggest that phosphotyrosines Y-1068 and Y-1173
      mediate the binding of Grb2 to the EGFR. Competition experiments with synthetic
      phosphopeptides corresponding to known autophosphorylation sites on the EGFR
      demonstrated that phosphopeptides containing Y-1068, and to a lesser extent Y
      1086, were able to inhibit the binding of Grb2 to the EGFR, while a Y-1173
      peptide did not. These findings were confirmed by using a dephosphorylation
      protection assay and by measuring the dissociation constants of Grb2's SH2 domain
      to tyrosine-phosphorylated peptides, using real-time biospecific interaction
      analysis (BIAcore). From these studies, we concluded that Grb2 binds directly to
      the EGFR at Y-1068, to a lesser extent at Y-1086, and indirectly at Y-1173. Since
      Grb2 also binds Shc after EGF stimulation, we investigated whether Y-1173 is a
      binding site for the SH2 domain of Shc on the EGFR. Both competition experiments
      with synthetic phosphopeptides and dephosphorylation protection analysis
      demonstrated that Y-1173 and Y-992 are major and minor binding sites,
      respectively, for Shc on the EGFR. However, other phosphorylation sites in the
      carboxy-terminal tail of the EGFR are able to compensate for the loss of the main
      binding sites for Shc. These analyses reveal a hierarchy of interactions between
      Grb2 and Shc with the EGFR and indicate that Grb2 can bind the tyrosine
      phosphorylated EGFR directly, as well as indirectly via Shc.

PMID- 7518561
TI  - Activation of p56lck by p72syk through physical association and N-terminal
      tyrosine phosphorylation.
AB  - The p56lck and p59fyn protein tyrosine kinases are important signal transmission
      elements in the activation of mature T lymphocytes by ligands to the T-cell
      antigen receptor (TCR)/CD3 complex. The lack of either kinase results in
      deficient early signaling events, and pharmacological agents that block tyrosine
      phosphorylation prevent T-cell activation altogether. After triggering of the
      TCR/CD3 complex, both kinases are moderately activated and begin to phosphorylate
      cellular substrates, but the molecular mechanisms responsible for these changes
      have remained unclear. We recently found that the p72syk protein tyrosine kinase
      is physically associated with the TCR/CD3 complex and is rapidly tyrosine
      phosphorylated and activated by receptor triggering also in T cells lacking
      p56lck. Here we examine the regulation of p72syk and its interaction with p56lck
      in transfected COS-1 cells. p72syk was catalytically active and heavily
      phosphorylated on its putative autophosphorylation site, Tyr-518/519. Mutation of
      these residues to phenylalanines abolished its activity in vitro and toward
      cellular substrates in vivo and reduced its tyrosine phosphorylation in intact
      cells by approximately 90%. Coexpression of lck did not alter the catalytic
      activity of p72syk, but the expressed p56lck was much more active in the presence
      of p72syk than when expressed alone. This activation was also seen as increased
      phosphorylation of cellular proteins. Concomitantly, p56lck was phosphorylated at
      Tyr-192 in its SH2 domain, and a Phe-192 mutant p56lck was no longer
      phosphorylated by p72syk. Phosphate was also detected in p56lck at Tyr-192 in
      lymphoid cells. These findings suggest that p56lck is positively regulated by the
      p72syk kinase.

PMID- 7518562
TI  - Csk suppression of Src involves movement of Csk to sites of Src activity.
AB  - Csk phosphorylates Src family members at a key regulatory tyrosine in the C
      terminal tail and suppresses their activities. It is not known whether Csk
      activity is regulated. To examine the features of Csk required for Src
      suppression, we expressed Csk mutants in a cell line with a disrupted csk gene.
      Expression of wild-type Csk suppressed Src, but Csk with mutations in the SH2,
      SH3, and catalytic domains did not suppress Src. An SH3 deletion mutant of Csk
      was fully active against in vitro substrates, but two SH2 domain mutants were
      essentially inactive. Whereas Src repressed by Csk was predominantly perinuclear,
      the activated Src in cells lacking Csk was localized to structures resembling
      podosomes. Activated mutant Src was also in podosomes, even in the presence of
      Csk. When Src was not active, Csk was diffusely located in the cytosol, but when
      Src was active, Csk colocalized with activated Src to podosomes. Csk also
      localizes to podosomes of cells transformed by an activated Src that lacks the
      major tyrosine autophosphorylation site, suggesting that the relocalization of
      Csk is not a consequence of the binding of the Csk SH2 domain to phosphorylated
      Src. A catalytically inactive Csk mutant also localized with Src to podosomes,
      but SH3 and SH2 domain mutants did not, suggesting that the SH3 and SH2 domains
      are both necessary to target Csk to places where Src is active. The failure of
      the catalytically active SH3 mutant of Csk to regulate Src may be due to its
      inability to colocalize with active Src.

PMID- 7518564
TI  - Dependence of transcriptional repression on CpG methylation density.
AB  - CpG methylation is known to suppress transcription. This repression is generally
      thought to be related to alterations of chromatin structure that are specified by
      the methylation. The nature of these chromatin alterations is unknown. Moreover,
      it has not been clear if the methylation repression occurs in an all-or-none
      fashion at some critical methylation density, or if intermediate densities of
      methylation can give intermediate levels of repression. Here I report a stable
      episomal system which recapitulates many dynamic features of methylation observed
      in the genome. I have determined the extent of transcriptional repression as a
      function of four densities of CpG methylation. I find that the repression is a
      graded but exponential function of the CpG methylation density such that low
      levels of methylation yield a 67 to 90% inhibition of gene expression. Higher
      levels of methylation extinguished gene expression completely. Transcription from
      methylated minichromosomes can be increased by butyrate treatment, suggesting
      that histone acetylation can reverse some of the repression specified by the
      methylated state. Sites of preferential demethylation occurred and may have
      resulted from transcription factor binding or DNA looping.

PMID- 7518563
TI  - A protein that is highly related to GTPase-activating protein-associated p62
      complexes with phospholipase C gamma.
AB  - p62 is a highly tyrosyl phosphorylated protein that was first identified in
      immunoprecipitates of the GTPase-activating protein (GAP) of p21ras from cells
      transformed by oncogenic nonreceptor tyrosine kinases or stimulated through
      tyrosine kinase receptors (C. Ellis, M. Moran, F. McCormick, and T. Pawson,
      Nature 343:377-381, 1991). In this article we describe a highly related 62-kDa
      protein that becomes tyrosyl phosphorylated and associated with phospholipase C
      gamma (PLC gamma) in C3H10T1/2 cells stimulated with epidermal growth factor
      (EGF) or transformed by v-src. GAP-associated and PLC gamma-associated p62
      comigrated in one-dimensional sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and exhibited nearly identical phosphotryptic peptide patterns.
      That the association of p62 with PLC gamma was direct and not mediated through
      binding of GAP-p62 to PLC gamma or to the EGF receptor (and coprecipitation of
      the receptor with PLC gamma) was demonstrated by (i) the inability to detect GAP
      in PLC gamma immunocomplexes or PLC gamma in GAP immunocomplexes, (ii) the
      association of p62 with PLC gamma in v-src-transformed cells in the absence of
      EGF stimulation, and (iii) in vitro solution binding and direct blotting of p62
      with a glutathione S-transferase fusion protein containing the Src homology 2
      (SH2) domains of PLC gamma. Unlike GAP, whose N-terminal SH2 mediates the
      interaction between GAP and p62, PLC gamma was found to require both its N- and C
      terminal SH2 regions for p62 binding. These studies demonstrate that a protein
      identical to or highly related to GAP-associated p62 binds PLC gamma and suggest
      a means by which "cross-talk" between PLC gamma- and GAP-mediated signalling may
      occur.

PMID- 7518567
TI  - Sequence restrictions in T cell receptor beta-chains that have specificity for a
      self-peptide/Ld complex.
AB  - Cytotoxic T lymphocytes that react with a complex of Ld and a ubiquitous self
      peptide derived from the enzyme alpha-ketoglutarate dehydrogenase (p2Ca,
      LSPFPFDL) can be readily elicited by the addition of synthetic peptide to
      cultures of BALB/c spleen cells. As with other Ld-restricted CTL, the p2Ca
      specific cells use predominantly the V beta 8.3 region. In addition, the p2Ca
      specific cells use almost exclusively one of three J beta gene segments.
      Selection for these J beta regions appears to be related to the presence of a
      glutamic acid residue that is encoded at the 5' end of the J beta and is present
      within the CDR3. As p2Ca does not contain a complementary charged residue, this
      finding may suggest that the beta-chain CDR3 from p2Ca-specific CTL contacts one
      of the five basic residues located on the Ld helices. Together, the results
      support the possibility that CDR1 and/or CDR2 (within V beta 8.3) and the CDR3
      may each contact the Ld molecule. In contrast to the V beta and J beta regions,
      the V beta D beta J beta junctions and V alpha J alpha repertoires were diverse.
      The diversity could explain why p2Ca-specific CTL have relatively high precursor
      frequencies allowing them to be generated rapidly in primary cultures.

PMID- 7518565
TI  - Protein-tyrosine phosphatase activity of CD45 is activated by sequential
      phosphorylation by two kinases.
AB  - We describe a potential regulatory mechanism for the transmembrane protein
      tyrosine phosphatase CD45. Phosphorylation on both tyrosine and serine residues
      in vitro results in an activation of CD45 specifically toward one artificial
      substrate but not another. The activation of these kinases appears to be order
      dependent, as it is enhanced when phosphorylation of tyrosine precedes that of
      serine but phosphorylation in the reverse order yields no activation. Any of four
      protein-tyrosine kinases tested, in combination with the protein-serine/threonine
      kinase, casein kinase II, was capable of mediating this activation in vitro. The
      time course of phosphorylation of CD45 in response to T-cell activation is
      consistent with the possibility that this regulatory mechanism is utilized in
      vivo.

PMID- 7518568
TI  - Evidence showing that the 1105 and 1106 isotypic residues of the fourth component
      of human complement, C4A, are not involved in amide bond formation.
AB  - Human C4A and C4B have different functions that may stem from their ability to
      bind hydroxyl or free amino groups on complement activating surfaces. Previous
      studies suggest that C4B binds to hydroxyl or amino groups whereas C4A binds to
      free amino groups on acceptor molecules. Comparison of the derived amino acid
      sequences of C4A and C4B has shown that differences exist between them at
      positions 1101, 1102, 1105 and 1106. These residues appear to be involved in the
      binding specificity of C4B. Less is known about the corresponding residues of
      C4A. It has been suggested that the aspartic acid of C4A at position 1106 is
      involved in amide bond formation by serving as a catalytic residue for the
      reaction or by promoting an increased interaction with amino nucleophilic groups.
      To examine the functional role of residues 1101-1106, we studied the effects of
      the C4A site-specific antipeptide mAb, AII-1 in assays dependent on the covalent
      binding properties of C4A; the C4 mediated inhibition of hemolysis and the C4
      mediated inhibition of immune precipitation. This study shows that mAb AII-1 has
      no effect on C4-mediated hemolysis or its ability to inhibit the rate of immune
      precipitate formation. The lack of interference by AII-1 in these assays could
      not be explained by low affinity interaction between antibody and C4A showing
      that mAb AII-1 does not affect the covalent binding activity of C4A. Furthermore,
      results from epitope mapping studies show that AII-1 binds to Leu1105 and Asp1106
      suggesting that these residues are not critical for amide bond formation by C4A.

PMID- 7518571
TI  - Counting polymers moving through a single ion channel.
AB  - The change in conductance of a small electrolyte-filled capillary owing to the
      passage of sub-micrometre-sized particles has long been used for particle
      counting and sizing. A commercial device for such measurements, the Coulter
      counter, is able to detect particles of sizes down to several tenths of a
      micrometre. Nuclepore technology (in which pores are etched particle tracks) has
      extended the lower limit of size detection to 60-nm particles by using a
      capillary of diameter 0.45 micron (ref. 4). Here we show that natural channel
      forming peptides incorporated into a bilayer lipid membrane can be used to detect
      the passage of single molecules with gyration radii as small as 5-15 A. From our
      experiments with alamethicin pores we infer both the average number and the
      diffusion coefficients of poly(ethylene glycol) molecules in the pore. Our
      approach provides a means of observing the statistics and mechanics of flexible
      polymers moving within the confines of precisely defined single-molecule
      structures.

PMID- 7518566
TI  - GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the
      placenta and pituitary gland.
AB  - The human glycoprotein hormone alpha-subunit gene is expressed in two quite
      dissimilar tissues, the placenta and anterior pituitary. Tissue-specific
      expression is determined by combinations of elements, some of which are common
      and others of which are specific to each tissue. In the placenta, a composite
      enhancer confers specific expression. It contains four protein-binding sites: two
      cyclic AMP (cAMP) response elements that bind CREB, a trophoblast-specific
      element that binds TSEB, and a sequence motif, AGATAA, that matches the consensus
      binding site for a family of transcription factors termed the GATA-binding
      proteins. In pituitary gonadotropes, the cAMP response elements remain important
      for expression, TSEB is absent, and elements further upstream participate in
      tissue-specific expression. Here we establish a regulatory role for the GATA
      element in both the placenta and pituitary by demonstrating that a mutation of
      this element decreases alpha-subunit gene expression 15-fold in JEG-3 human
      placental cells and 2.5-fold in alpha T3-1 mouse pituitary gonadotropes. In JEG-3
      cells, human GATA-2 (hGATA-2) and hGATA-3 are highly expressed and both proteins
      bind to the alpha-subunit gene GATA element. In alpha T3-1 cells, the GATA motif
      is bound by mouse GATA-2 (mGATA-2) and an mGATA-4-related protein. Cotransfection
      of hGATA-2 or hGATA-3 into alpha T3-1 cells activates the alpha-subunit gene
      threefold. These studies establish a role for the GATA-binding proteins in
      placental and pituitary alpha-subunit gene expression, significantly expanding
      the known target genes of GATA-2, GATA-3, and perhaps GATA-4.

PMID- 7518570
TI  - Cardiac physiology. Endothelin to the rescue?

PMID- 7518572
TI  - Inhibition by morphine of the cardiovascular and behavioral responses evoked by
      centrally administered substance P in conscious rats.
AB  - The effect of endogenous opioid receptor stimulation on the central
      cardiovascular and behavioral actions of substance P (SP) was examined in
      conscious rats. SP (55 pmol) injected intracerebroventricularly (i.c.v.) elicited
      increases in mean arterial pressure, heart rate, and stereotyped behavioral
      activation such as exploring and grooming, which were considered to be parts of
      the cardiovascular defense reaction. Intravenous (i.v.) pretreatment with
      morphine (2.5 and 5.0 mg/kg) attenuated the cardiovascular and behavioral
      responses produced by SP i.c.v. dose-dependently. The i.v. pretreatment with
      naloxone (10 mg/kg) had no effect on the central SP-induced response. Pressor
      responses elicited by i.c.v. injection of corticotropin-releasing factor or
      angiotensin II were also attenuated by pretreatment with i.v. morphine (5.0
      mg/kg). Our results showed that endogenous opioid receptor stimulation
      antagonizes the central cardiovascular and behavioral actions of SP. Morphine may
      not influence the primary site of action of SP but does influence the central
      neural pathway which conveys the SP-induced sympathetic activation signal.

PMID- 7518573
TI  - Inhibition of nitric oxide synthase attenuates the development of morphine
      tolerance and dependence in mice.
AB  - The effect of the nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl
      ester (L-NAME, 5-20 mg/kg i.p.) and NG-nitro-L-arginine (NO2Arg, 5-20 mg/kg i.p.)
      on morphine-induced analgesia, as well as on morphine induced tolerance and
      dependence was examined in male albino Swiss mice. Neither acute nor repeated
      (for 5 days) administration of the nitric oxide synthase inhibitor, L-NAME
      affected the morphine induced analgesia, as measured by hot plate and tail-flick
      tests. On the other hand, administration of L-NAME or NO2Arg along with morphine
      prevented the development of tolerance to the analgesic effect of morphine for at
      least 7 days, whereas the analgesic effect of morphine alone disappeared after 5
      days. L-NAME and NO2Arg also attenuated some signs of morphine dependence, as
      assessed by naloxone (2 mg/kg)-precipitated withdrawal. These results indicate
      that NO may play a role in the development of morphine tolerance and dependence.

PMID- 7518574
TI  - Outcome at 2 years of infants less than 1000 grams: a regional study.
AB  - AIMS: To determine the neurodevelopmental outcome of infants with birthweight <
      1000 g at 2 years. METHODS: Prospective, regional case-control cohort. RESULTS:
      Of 141 liveborn infants with birthweight between 500-999 g born to mothers of
      central North Island domicile, 83 (58.9%) were alive at 2 years. Sixty nine of
      the survivors completed a neurodevelopmental assessment at a corrected age of 2
      years along with 29 control infants. Neurological disability was present in 27.5%
      of survivors, and 20.7% of controls, with severe disability being more prevalent
      amongst survivors (10.1% vs 3.4%). The mean developmental index, expressive and
      receptive language scores were not significantly different between the groups.
      CONCLUSION: Infants with birthweight < 1000 g are at increased risk of major
      neurodevelopmental disability at age 2 years compared with a control cohort.

PMID- 7518569
TI  - Serological and biochemical characterization of recombinant baculovirus
      carcinoembryonic antigen.
AB  - Carcinoembryonic antigen (CEA), a glycosylated protein of M(r) 180 kDa, is one of
      the most widely used human tumor markers. A majority of gastrointestinal cancers
      as well as breast and nonsmall cell lung carcinomas express CEA. We have
      previously described a recombinant baculovirus BVCEA-140 expressing the full
      length human CEA and a variant, BVCEA-16, that encodes only the NH2-terminal
      domain, as well as a recombinant (BVNCA) expressing the closely related molecule
      nonspecific cross-reactive antigen (NCA). We have now compared a panel of 24 anti
      CEA and anti-NCA monoclonal antibodies (MAbs) for their ability to bind to these
      recombinant CEA and NCA proteins, as well as with a new 60 kDa subgenomic form
      designated BVCEA-60. The epitope mapping studies indicate that all the CEA
      specific MAbs can recognize BVCEA-140. We also compared the sugar composition of
      BVCEA-140 to native CEA, using a lectin-linked immunoradiometric assay. The
      results demonstrated that both the native and recombinant baculovirus CEA contain
      simple high-mannose carbohydrates as well as biantennary and biantennary hybrid
      complexes. However, native CEA also contains triantennary and tetraantennary
      complex sugars, while the recombinant CEA molecule does not. Immunogenicity of
      the recombinant CEA molecules was demonstrated in mice. ELISA and Western blot
      analyses were used to determine the cross-reactivity of the anti-CEA sera. Mice
      immunized with BVCEA-140 elicit antibodies that are reactive to native CEA. When
      the BVCEA-16 was used as an immunogen, the antisera failed to detect native CEA
      or BVCEA-140. These studies demonstrate that minor sugar differences exist
      between native and baculovirus-derived CEA. However, epitope mapping with a panel
      of 24 anti-CEA MAbs (recognizing at least 10 CEA epitopes) stowed virtual
      immunologic identity between these two molecules. Moreover, BVCEA-140 appears to
      be a more potent humoral immunogen in mice than native CEA. These purified
      recombinant proteins can thus serve as standards in CEA serum assays for the
      possible detection and characterization of cell-mediated immune responses to CEA
      and as a potential source of immunogen (primary or for boosting) for active
      specific immunotherapy protocols of human carcinomas.

PMID- 7518575
TI  - Long-term outcomes after the surgical removal of advanced subfoveal neovascular
      membranes in age-related macular degeneration.
AB  - BACKGROUND: The poor results of laser photocoagulation in patients with age
      related macular degeneration who have subfoveal neovascular membranes, as
      reported by the Macular Photocoagulation Study Group, have posed the question as
      to whether the surgical removal of the neovascular membranes by subfoveal surgery
      might provide superior functional results, possibly in subgroups of patients.
      METHODS: The authors' first ten patients treated by subfoveal surgery were
      followed prospectively. Follow-up of a mean duration of 2 years is presented,
      with particular emphasis on visual and anatomic outcomes. Preoperative subfoveal
      choroidal neovascular membranes and postoperative retinal pigment epithelial
      defects were measured using digitized planimetry. RESULTS: Initial visual
      acuities were equal to or less than 20/400, with a mean duration of visual loss
      of 8 months. The mean choroidal neovascular membrane size was 7 disc areas. Eight
      of ten patients improved one to two lines of Snellen visual acuity
      postoperatively. One patient achieved visual acuity of 20/60 at 15 months before
      declining because of recurrent neovascularization. Surgically induced retinal
      pigment epithelial defects were invariable; the mean defect was 14 standard disc
      areas in size. Choriocapillaris atrophy and focal losses of deeper choroidal
      tissue also occurred. Surgical complications were frequent but responded to
      routine management. The authors observe a 2-year recurrence rate of 40%.
      Recurrences often are atypical, fibrous, and poorly vascularized. CONCLUSIONS:
      Although substantial visual improvements are common, long-term reading vision has
      not been achieved. Retinal pigment epithelial incorporation into late subfoveal
      membranes remains a major limiting factor. The role of early surgery and the role
      of surgery for patient subgroups need to be compared directly with the results of
      foveal laser treatment, using several visual outcomes.

PMID- 7518578
TI  - Differential binding of pp60c-src and pp60v-src to cytoskeleton is mediated by
      SH2 and catalytic domains.
AB  - The transforming protein of Rous sarcoma virus, pp60v-src, and its normal
      cellular homolog, pp60c-src, differ not only in oncogenic potential but also in
      their subcellular localization and cytoskeletal binding ability. pp60v-src has
      been shown to stably associate with a detergent-insoluble cytoskeletal matrix,
      whereas pp60c-src does not. We have generated a series of precise deletion and
      truncations of the Src homology domains within pp60v-src and pp60c-src, based on
      the crystal and solution structures of these regions, to determine not only the
      region responsible for cytoskeletal association but also the mechanism accounting
      for the differential binding observed. Here we show that the SH2 domain, but not
      the SH3 domain, mediates cytoskeletal association of pp60v-src through a
      phosphotyrosine-dependent interaction. The ability to interact with the
      cytoskeletal matrix is regulated by the catalytic (SH1) domain. Truncation of the
      pp60v-src catalytic domain results in lower binding while removal of the
      catalytic domain of pp60c-src results in the acquisition of cytoskeletal binding
      similar to that of the analogous v-src construct. These results indicate that the
      SH2 and catalytic domains function coordinately to regulate the cytoskeletal
      association of pp60v-src and pp60c-src.

PMID- 7518576
TI  - Allelic loss and somatic differentiation in human male germ cell tumors.
AB  - The complex but poorly understood human male germ cell tumors offer unusual
      opportunities for the genetic analysis of malignant transformation and embryonal
      differentiation in a pluripotential stem cell lineage. Histologically, these
      tumors are divided into two major subgroups, seminomas which are characterized by
      inability to express embryonal differentiation, and non-seminomas which are
      characterized by ability to express embryonal as well as extra-embryonal patterns
      of differentiation. To understand the role of genetic factors in the development
      of these tumors and the regulation of differentiation expressed by them, we
      carried out a detailed allelotype analysis by the loss of heterozygosity assay.
      This analysis revealed frequent deletions in known tumor suppressor genes (RB1,
      DCC, NME), a number of previously described sites of candidate tumor suppressor
      genes (3p, 9p, 9q, 10q, 11p, 11q and 17p), as well as several novel sites (2p,
      3q, 5p, 12q, 18p and 20p). Our results also showed that well differentiated
      teratomas exhibit a significantly higher level of allelic loss compared to the
      less differentiated embryonal carcinomas. In addition, certain loci and genes
      exhibited frequent non-random deletion in teratomas (D3S32, D3S42, D5S12, D10S25,
      D11S12, RB1, TP53, NME1, NME2, D17S4, D18S6 and D20S6) and embryonal carcinomas
      (IFNB, D9S27). Among these loci, the NME genes were notable for a high degree of
      genetic loss (> 70%) in teratomas. These results suggested that nonrandom loss or
      inactivation of certain genes may be associated with tumor development and loss
      or inactivation of other genes may be associated with somatic differentiation.

PMID- 7518577
TI  - Cell fractionation in non-ionic detergent distinguishes sub-populations of
      polyoma virus middle T antigen and reveals a novel form.
AB  - The transforming function of polyoma virus, middle T antigen (MT), interacts with
      several cellular enzymes, essential to its oncogenic activity. We have used cell
      fractionation to study the various MT/cellular protein complexes. We demonstrate
      that MT can be separated into three sub-species, dependent upon extraction in two
      buffers that we designate A and B: Antigen extracted from whole cells by both
      buffers (called MT1) is associated with most of the phosphorylated phosphatidyl
      inositol kinase 85 kD subunit, pp85, and protein phosphatase 2A. Antigen (MT2),
      associated with the greater portion of pp60c-src, is extracted by buffer B, but
      not buffer A. A third population (MT3), resistant to extraction by either buffer,
      is not detectably associated with protein phosphatase 2A or pp85. It is, however,
      associated with a low level kinase activity. The interaction between pp60c-src
      and MT appears to influence the formation of both MT2 and MT3. MT2 fractionates
      with the cellular microtubule network, but does not appear to be directly
      associated with it. MT3, a previously undescribed population, comprises about one
      third of MT in wild type antigen-containing cells. It is missing in mutants
      incapable of interacting with pp60c-src, but exists in the absence of an
      interaction with pp85. We suggest that MT3 may be an intermediate in, or product
      of, one of the MT/pp60c-src signalling pathways, distinct from that involving
      pp85.

PMID- 7518579
TI  - JAK3: a novel JAK kinase associated with terminal differentiation of
      hematopoietic cells.
AB  - The Janus Kinases (JAK) JAK1, JAK2, and TYK2 are protein tyrosine kinases which
      play a pivotal role in the signal transduction process mediated by cytokines.
      These kinases appear to transduce signals via their substrates which modulate
      programs of gene expression specific to the respective signals. It is becoming
      increasingly evident that certain cytokines such as Granulocyte Colony
      Stimulating Factor (GCSF) can transmit signals for both cellular proliferation
      and differentiation. It is at present unclear whether both of these signals are
      transmitted by the same JAK kinase or whether an entire family of such kinases
      are involved in this process. To determine if additional members of JAK kinase
      family exist, we designed a polymerase chain reaction based strategy which
      resulted in the identification of a new member of the JAK kinase family. This new
      kinase, which we have named JAK3 is encoded by a 4.3 kb mRNA transcript.
      Nucleotide sequence analysis of a full length cDNA derived from this mRNA
      revealed that it encodes an open reading frame of 3897 bp. The protein encoded by
      this mRNA contains the double catalytic domain characteristic of the JAK family
      kinases. The most striking difference between JAK3 and the other JAK kinases is
      the presence of two stretches of additional amino acid sequence of 147 and 28
      residues which span between amino acid positions 322 to 469 and 632 to 660
      respectively. Expression studies indicate that JAK3 is expressed at very low
      levels in immature hematopoietic cells, but its expression is dramatically up
      regulated during terminal differentiation of these cells. These results suggest
      that JAK3 plays an important role in the differentiation of hematopoietic cells.

PMID- 7518583
TI  - Removal of t-butyldimethylsilyl protection in RNA-synthesis. Triethylamine
      trihydrofluoride (TEA, 3HF) is a more reliable alternative to tetrabutylammonium
      fluoride (TBAF).

PMID- 7518582
TI  - Circular RNA oligonucleotides. Synthesis, nucleic acid binding properties, and a
      comparison with circular DNAs.
AB  - We report the synthesis and nucleic acid binding properties of two cyclic RNA
      oligonucleotides designed to bind single-stranded nucleic acids by pyr.pur.pyr
      type triple helix formation. The circular RNAs are 34 nucleotides in size and
      were cyclized using a template-directed nonenzymatic ligation. To ensure isomeric
      3'-5' purity in the ligation reaction, one nucleotide at the ligation site is a
      2'-deoxyribose. One circle (1) is complementary to the sequence 5'-A12, and the
      second (2) is complementary to 5'-AAGAAAGAAAAG. Results of thermal denaturation
      experiments and mixing studies show that both circles bind complementary single
      stranded DNA or RNA substrates by triple helix formation, in which two domains in
      a pyrimidine-rich circle sandwich a central purine-rich substrate. The affinities
      of these circles with their purine complements are much higher than the
      affinities of either the linear precursors or simple Watson-Crick DNA
      complements. For example, circle 1 binds rA12 (pH 7.0, 10 mM MgCl2, 100 mM NaCl)
      with a Tm of 48 degrees C and a Kd (37 degrees C) of 4.1 x 10(-9) M, while the
      linear precursor of the circle binds with a Tm of 34 degrees C and a Kd of 1.2 x
      10(-6) M. The complexes of circle 2 are pH-dependent, as expected for triple
      helical complexes involving C(+)G.C triads, and mixing plots for both circles
      reveal one-to-one stoichiometry of binding either to RNA or DNA substrates.
      Comparison of circular RNAs with previously synthesized circular DNA
      oligonucleotides of the same sequence reveals similar behavior in the binding of
      DNA, but strikingly different behavior in the binding of RNA. The cyclic DNAs
      show high DNA-binding selectivity, giving relatively weaker duplex-type binding
      with complementary RNAs. The relative order of thermodynamic stability for the
      four types of triplex studied here is found to be DDD >> RRR > RDR >> DRD. The
      results are discussed in the context of recent reports of strong triplex
      dependence on RNA versus DNA backbones. Triplex-forming circular RNAs represent a
      novel and potentially useful strategy for high-affinity binding of RNA.

PMID- 7518581
TI  - Interactions between yeast TFIIIB components.
AB  - Yeast transcription factor TFIIIB is a multicomponent factor comprised of the
      TATA-binding protein TBP and of associated factors TFIIIB70 and B". Epitope
      tagged or histidine-tagged TFIIIB70 could be quantitatively removed from TFIIIB
      by affinity chromatography. TBP and B" (apparent mass 160-200 kDa) could be
      easily separated by gel filtration or ion-exchange chromatography. While only
      weak interactions were detected between TBP and B", direct binding of [35S]
      labeled TBP to membrane-bound TFIIIB70 could be demonstrated in absence of DNA.
      On tRNA genes, there was no basal level of transcription in the complete absence
      of TBP. The two characterized TFIIIB components (recombinant rTFIIIB70 and rTBP)
      and a fraction cochromatographing with B" activity were found to be required for
      TFIIIC-independent transcription of the TATA-containing U6 RNA gene in vitro.
      Therefore, beside the TFIIIC-dependent assembly process, each TFIIIB component
      must have an essential role in DNA binding or RNA polymerase recruitment.

PMID- 7518585
TI  - 3rd International Congress on Rate Adaptive Cardiac Pacing and Implantable
      Defibrillators. Proceedings. Munich, October 1993.

PMID- 7518587
TI  - Anticoagulants: when and how?

PMID- 7518584
TI  - Atrial fibrillation: new aspects of an old problem.

PMID- 7518586
TI  - Incidence and risks associated with atrial fibrillation.

PMID- 7518588
TI  - Indications and limitations of class I drugs in atrial fibrillation.

PMID- 7518589
TI  - Indications and limitations of class II and III antiarrhythmic drugs in atrial
      fibrillation.
AB  - In summary, the Class III antiarrhythmic agents amiodarone and sotalol are
      effective in restoring sinus rhythm in patients with chronic atrial fibrillation
      with a higher effectiveness of amiodarone. Both agents successfully prevent
      recurrent episodes of atrial fibrillation after electrical cardioversion and both
      can control heart rate in persistent atrial fibrillation. Amiodarone appears to
      be particularly suitable in patients with atrial fibrillation and concomitant
      congestive heart failure because it lacks clinically relevant negative inotropic
      activity. Both substances are also effective in controlling ventricular
      arrhythmias that are frequently present in patients with atrial fibrillation.
      Finally, both drugs possess antiadrenergic activity, which makes the substances
      particularly attractive in patients with coronary heart disease as the underlying
      cause of atrial fibrillation.

PMID- 7518580
TI  - Summary: the modified nucleosides of RNA.
AB  - A comprehensive listing is made of posttranscriptionally modified nucleosides
      from RNA reported in the literature through mid-1994. Included are chemical
      structures, common names, symbols, Chemical Abstracts registry numbers (for
      ribonucleoside and corresponding base), Chemical Abstracts Index Name,
      phylogenetic sources, and initial literature citations for structural
      characterization or occurrence, and for chemical synthesis. The listing is
      categorized by type of RNA: tRNA, rRNA, mRNA, snRNA, and other RNAs. A total of
      93 different modified nucleosides have been reported in RNA, with the largest
      number and greatest structural diversity in tRNA, 79; and 28 in rRNA, 12 in mRNA,
      11 in snRNA and 3 in other small RNAs.

PMID- 7518590
TI  - Status of ablation in patients with atrial tachycardia and flutter.
AB  - RF catheter ablation directed at the atrial substrate is a safe and effective
      means of treating patients with drug refractory atrial tachycardias and atrial
      flutter, avoiding the need for His-bundle ablation and permanent pacing. While
      further follow-up will be needed to evaluate the incidence of later recurrence or
      emergence of new arrhythmias, this is a promising technique for a growing cohort
      of patients.

PMID- 7518591
TI  - Comparison of atrial ventricular fibrillation and defibrillation.

PMID- 7518592
TI  - Lead systems for atrial defibrillation.
AB  - In summary, these five studies show that electrode locations that include both
      left and right atrium result in lower thresholds. Thresholds from right atrium to
      chest wall patch are higher than thresholds from right atrium to cardiac vein,
      suggesting that confinement of the electric field by a transvenous electrode
      system is advantageous. Of the transvenous locations tested, the right atrial
      appendage to left atrial appendage defibrillation vector consistently had the
      lowest defibrillation energy threshold. The proximal coronary sinus to right
      atrial vector may be inappropriate due to the high thresholds observed. The large
      variability of the mean threshold for the obtuse marginal location in the cardiac
      vein vasculature suggests that this vector may result in higher thresholds in
      some instances. Electrode locations that have high defibrillation thresholds and
      are in close proximity to the sinoatrial or atrioventricular node increase the
      likelihood of sinus arrhythmias or conduction block following the defibrillation
      shocks. No difference was detected between the thresholds between the single
      catheter, two electrode system and the two catheter system, despite the
      variability of location of the electrode in the right atrium, suggesting that
      such a catheter may provide a simpler implantation procedure and equivalent
      thresholds in some patients. These findings suggest that coronary sinus/great
      cardiac vein catheter designs should strive for implantation in the distal
      portion of the great cardiac vein so that the shocking electrode underlies the
      left atrium with the other shocking electrode located in the right atrium.

PMID- 7518593
TI  - Impact of pulse characteristics on atrial defibrillation energy requirements.
AB  - In summary, many issues pertaining to pulse characteristics and atrial
      defibrillation remain unsolved. Perhaps the most burning questions are whether a
      further reduction in atrial defibrillation energy requirements can be achieved by
      the combination of biphasic waveforms with dual pathway sequential shocks to
      produce a more homogenous distribution of charge, whether right and left atrial
      polarity of the first phase of asymmetrical biphasic shocks can reduce energy
      requirements in individual patients and whether the delivery of very long
      biphasic shocks (possibly > 20 msec) can reduce the discomfort of shorter shocks
      by decreasing the peak current density. Only then will the wide-spread acceptance
      of the implantable atrial defibrillator become closer to reality.

PMID- 7518596
TI  - Detection of occult micrometastases in the bone marrow of patients with prostate
      carcinoma.
AB  - A panel of three monoclonal antibodies that recognize membrane and cytoskeletal
      antigens expressed by epithelial cells (T16, C26, and AE-1) was used in a
      sensitive immunohistochemical assay to detect tumor cells in bone marrow
      aspirates from 20 patients with prostate cancer. Bone marrow aspirates from 2/9
      (22%) patients with localized prostate cancer (stage B, 0/5; Stage C, 2/4), and
      4/11 (36%) patients with metastatic prostate cancer (Stage D1, 0/7 patients;
      Stage D2, 4/4 patients) had antigen-positive cells in their bone marrow. The
      patients with localized disease had conventional examinations for metastases,
      including radioisotope bone scans and examination of bone marrow cytology, which
      were negative. The serum prostatic specific antigen (PSA) level appeared to
      correlate with the presence of micrometastases. Those patients with localized
      disease and antigen-positive cells in the bone marrow had an average serum PSA
      level of 26.6 ng/ml, while the average serum PSA level in patients without
      antigen-positive cells was 12.3 ng/ml. In addition, the number of antigen
      positive cells detected appeared to correlate with the stage of disease; patients
      with Stage C prostate cancer had an average of 10 antigen-positive cells per one
      million bone marrow elements, while patients with Stage D2 disease had an average
      of 25 antigen-positive cells per one million bone marrow elements. We have
      demonstrated that immunohistochemical staining of bone marrow aspirates can
      detect occult bone marrow metastases in patients with apparently localized
      prostate cancer. Further follow-up of these and a larger number of patients will
      be require to determine the potential clinical significance of this finding.

PMID- 7518595
TI  - Initial experience with intracardiac atrial defibrillation in patients with
      chronic atrial fibrillation.

PMID- 7518594
TI  - Catheter based atrial defibrillation.

PMID- 7518599
TI  - Relationship between serum prostate specific antigen and histological prostatitis
      in patients with benign prostatic hyperplasia.
AB  - The relationship between the serum values of prostate specific antigen (PSA) and
      the extent of histological prostatitis was investigated in 42 patients undergoing
      transurethral resection of the prostate for benign hyperplasia (BPH) without
      clinical evidence of prostatitis. Histological prostatitis was divided into three
      groups: acute, chronic-active, and chronic-inactive inflammation. The extent of
      histological prostatitis was expressed as the number of prostatic acinar and
      ductal glands with inflammatory infiltrate per total number of glands (%). The
      serum PSA values significantly correlated with the extent of acute and chronic
      active prostatitis (correlation coefficient r = 0.765 and 0.656, P < 0.01). A
      relationship between PSA values and the extent of chronic-inactive prostatitis
      was not found. In the immunohistochemical study, prostatic epithelial cells with
      acute and chronic-active inflammation showed negative staining for PSA antigen.
      These results indicate that histological acute and chronic-active prostatitis is
      considered an important factor for inducing the high increase in serum PSA values
      via the leak phenomenon.

PMID- 7518598
TI  - Androgen ablation induces tenascin expression in the rat prostate.
AB  - Tenascin is a glycoprotein of the extracellular matrix of mesenchymal derived
      tissue compartments. Although the DNA sequences that code for tenascin production
      are known and the protein structure is well characterized, little is known about
      regulation of tenascin expression. Therefore, we are interested in hormonal
      aspects of tenascin expression. In this study, we addressed the question if
      androgen deprivation and prostatic involution would influence tenascin expression
      in the prostate. Methodologically, in two series of experiments, intact and
      orchiectomized testosterone propionate substituted male rats were subjected to
      one of the following hormonal treatments: a) flutamide, b) the antiandrogen
      casodex, and c) cyproterone acetate (CPA). As controls in each series, we used
      untreated controls and orchiectomized rats. After a period of 14 days of
      treatment, prostates were removed. Tenascin immunostaining of the sectioned
      specimen from the control and the hormonally treated animals demonstrated the
      following: 1) Little, if any tenascin immunoreactivity was detectable in
      prostates of untreated animals. 2) Androgen deprivation with either treatment
      resulted in tenascin expression in the stroma of the prostates. 3) Tenascin
      expression appeared to be variable both semiquantitatively and in the staining
      pattern detectable except in prostates treated with CPA, in which we observed the
      most uniform and most widespread staining pattern. From these results, we
      conclude that androgen deprivation induces tenascin expression in the stroma of
      the involuting prostate. Remodelling of the extracellular matrix of the stroma,
      known to appear in the process of prostate involution by androgen ablation,
      represents a process which has not been discussed with tenascin expression so
      far.

PMID- 7518597
TI  - Smooth muscle contractility in prostatic hyperplasia: role of cyclic adenosine
      monophosphate.
AB  - The role of cyclic 3'-5' adenosine monophosphate (cAMP) on alpha 1-adrenoceptor
      (alpha 1-receptor) induced smooth muscle contractions in symptomatic benign
      prostatic hyperplasia (BPH) was investigated. Application of the selective alpha
      1-receptor agonist phenylephrine (PE) induced fully reversible contractions in a
      dose-dependent fashion. Phosphodiesterase (PDE) inhibitors blocking the
      degradation of cAMP suppressed the PE induced contractions as follows:
      theophylline (1 mM), 91.1 +/- 1.4%; papaverine (0.5 mM), 822.8 +/- 3.2%;
      milrinone (0.5 mM), 68.2 +/- 0.6%. Forskolin (50 microM), which elevates cAMP
      through direct activation of adenylatecyclase (AC), inhibited the PE induced
      contractions by 82.4 +/- 3.6%. To further increase the intracellular cAMP
      concentration ([cAMP]i), the membrane permeable cAMP analogue N6-2'-O
      dibutyryladenosine derivative (dBcAMP; 1 mM) was applied and reduced the PE
      evoked contractions by 69.8 +/- 2.3%. We conclude that elevation of [cAMP]i is an
      important step in inducing smooth muscle relaxation.

PMID- 7518600
TI  - Correlation of mild pre-school developmental delay and subsequent learning
      abilities: a health and education perspective.
AB  - This article examines the correlation of milder pre-school neuro-developmental
      functional delay and school learning abilities from a clinical and educational
      perspective. A positive high correlation was found. Developmental function was
      therefore judged to be highly relevant to learning skills. A screening and
      assessment scheme is suggested.

PMID- 7518601
TI  - Functional effects of a family of galanin antagonists on the cardiovascular
      system in anaesthetised cats.
AB  - Previous studies have shown that injection of galanin (GAL: 6.2 nmol/kg) causes
      prolonged inhibition of cardiac vagal action in anaesthetised cats. Stimulation
      of the cardiac sympathetic nerve (16 Hz for 5 min) also produces inhibition of
      cardiac vagal action, an effect which has been proposed to be due to the release
      of endogenous GAL from sympathetic nerves. In a previous study we tested
      galantide (M15) and in this study we compared galantide with two other GAL
      antagonists for their GAL antagonist activity in our experimental model. Each of
      these incorporate the N-terminal fragment GAL 1-13 and a C-terminal portion of
      another bioactive peptide and all are C-terminally amidated. GAL 1-13 Substance P
      5-11 amide (galantide: M15: 62 nmol/kg and 156 nmol/kg), GAL 1-13 Spantide amide
      (C7: 156 nmol/kg) and GAL 1-13 NPY 24-36 amide (M32a: 62 nmol/kg) all
      significantly reduced the cardiac vagal inhibitory effect of exogenous GAL and
      also reduced the effect of sympathetic stimulation on subsequent cardiac vagal
      slowing, giving strong support to our hypothesis that GAL is involved in this
      phenomenon. No antagonist reduced the depressor effect of GAL. This study
      demonstrates the GAL antagonist properties of these agents on autonomic
      neuroeffector functions making them useful tools in elucidating further functions
      of endogenous GAL.

PMID- 7518602
TI  - Changes of spinal substance P, calcitonin gene-related peptide, somatostatin, Met
      enkephalin and neurotensin in rats in response to formalin-induced pain.
AB  - Changes of substance P (SP)-, calcitonin gene-related peptide (CGRP)-,
      somatostatin (SS)-, Met-enkephalin (Met-Enk)- and neurotensin (NT)-
      immunoreactive materials on two sides of the lumbar dorsal horn were inspected
      microscopically and quantified with a computer-assisted image processing system
      in rats with intact or totally transected spinal cord 2 h after injection of 0.2
      ml of 0.5% formalin into the right hindpaw subcutaneously. The results showed
      that the SP-like immunoreactivity (SP-LI), CGRP-LI, SS-LI, Met-Enk-LI, and NT-LI
      were significantly higher in fibers and terminals in superficial laminae of the
      dorsal horn ipsilateral to the formalin injection in both of the experimental
      groups. It is supposed that the increased contents of these peptides reflect an
      increased biosynthesis, transport, and release of these peptides in primary
      afferents and spinal intrinsic neurons in response to the long-lasting inflow of
      noxious messages, and that these changes seem to be produced even in the
      condition when the supraspinal effects have been excluded.

PMID- 7518603
TI  - The role of neuropeptides in the regulation of adrenal vascular tone: effects of
      vasoactive intestinal polypeptide, substance P, neuropeptide Y, neurotensin, Met
      enkephalin, and Leu-enkephalin on perfusion medium flow rate in the intact
      perfused rat adrenal.
AB  - There is evidence that adrenal blood flow may be regulated in part by
      neuropeptides released from the capsular region of the adrenal gland in response
      to splanchnic nerve stimulation. The present study investigated the effects of
      various neuropeptides on the rate of perfusion medium flow through an intact in
      situ perfused rat adrenal preparation. Vasoactive intestinal polypeptide (VIP)
      had the greatest effect, causing a 136% increase in flow at the highest dose used
      (10 nmol in a 200 microliters bolus). Of the other peptides tested Met-enkephalin
      caused a 50% increase in flow, and the others (Leu-enkephalin, neurotensin and
      substance P) had only a minor effect, increasing perfusion medium flow rate by no
      more than around 35%. Neuropeptide Y, in contrast, caused a significant decrease
      in perfusion medium flow rate: the maximum effect was a 30% decrease with a dose
      of 1 nmol in a 200 microliters bolus. The significance of this observation awaits
      elucidation. It is clear from the actions of the neuropeptides tested that they
      may have a significant role in the regulation of adrenal blood flow. In view of
      the findings of other authors: that VIP is released in response to splanchnic
      nerve stimulation, and that it is specifically localised in the capsular region
      of the adrenal, it seems most likely that VIP is the major peptide involved in
      mediating the increased adrenal blood flow following splanchnic nerve
      stimulation.

PMID- 7518604
TI  - Clinicopathologic correlation of choroidal neovascularization demonstrated by
      indocyanine green angiography in a patient with retention of good vision for
      almost four years.
AB  - OBJECTIVE: The clinicopathologic features of age-related macular degeneration
      (AMD) with occult choroidal neovascularization (CNV) detected by digital
      indocyanine green (ICG) videoangiography in an 82-year-old woman are discussed.
      METHODS: Serial sections through the macula of both eyes were prepared, and two
      dimensional reconstruction maps depicting the histopathologic features were
      drawn. A technique by which electron microscopic examination of sections removed
      from glass slides was performed is described. RESULTS: Histopathologic
      examination of the lesion disclosed a 3.5 mm x 0.02 mm thick fibrovascular
      subretinal pigment epithelial choroidal neovascular membrane in an eye with
      diffuse basal laminar deposit in the macula. CONCLUSION: This case represents the
      first clinicopathologic correlation involving ICG videoangiography of CNV. The
      findings support the growing clinical impression that ICG videoangiography is of
      value in identifying what has been previously described as ill-defined or occult
      CNV.

PMID- 7518605
TI  - Surgical removal of an extrafoveal fibrotic choroidal neovascular membrane with
      foveal serous detachment in age-related macular degeneration.
AB  - BACKGROUND: Visual recovery after submacular surgery for age-related macular
      degeneration (AMD) has been very limited. METHODS: A patient with an extrafoveal
      fibrotic choroidal neovascular membrane from AMD had an overlying serous foveal
      detachment with the fibrotic tissue elevating the foveal retina. Photocoagulation
      of the neovascular membrane was not recommended because of its nonpigmented,
      fibrotic nature. The membrane was surgically excised. RESULTS: Preoperative and
      postoperative visual acuity and central 30 degrees visual fields were followed.
      Visual acuity improved from 20/200 to 20/25, and a preoperative central scotoma
      resolved completely 18 months after surgical excision of the extrafoveal fibrotic
      neovascular membrane. There were no intraoperative or postoperative
      complications. CONCLUSION: This type of patient may represent a distinct subset
      of patients with AMD amenable to subretinal surgery who could potentially have
      good recovery of vision.

PMID- 7518606
TI  - Foveal sparing photocoagulation for exudative age-related macular degeneration.
AB  - BACKGROUND: The use of laser photocoagulation with sparing of foveal
      photoreceptors to control exudative age-related macular degeneration (AMD) with
      subfoveal involvement was investigated. METHODS: Patients with exudative AMD and
      visual acuity of 20/100 or worse were treated with foveal-sparing laser
      photocoagulation. The full extent of the choroidal neovascular membrane was
      treated with laser photocoagulation in addition to any associated retinal pigment
      epithelial detachment, with sparing of the foveal avascular zone. Three cases in
      which visual acuity improved dramatically are presented. RESULTS: Laser
      photocoagulation resulted in control of the exudative process in all patients.
      The three patients whose cases are presented had dramatic visual improvement.
      CONCLUSION: Foveal-sparing laser photocoagulation is an alternative treatment
      modality in patients with exudative AMD involving the fovea. The definitive value
      of this treatment modality can only be determined by a prospective, randomized,
      clinical trial.

PMID- 7518607
TI  - Analysis of vascularized pigment epithelial detachments using indocyanine green
      videoangiography.
AB  - BACKGROUND: Occult choroidal neovascularization (CNV) secondary to age-related
      macular degeneration (AMD) is known to occur with and without an associated
      serous pigment epithelial detachment (PED). Digital indocyanine green (ICG)
      videoangiography has been reported to provide enhanced definition of occult CNV.
      METHODS: A total of 244 of 657 (37%) consecutive patients with AMD, with occult
      CNV and an associated serous PED evident on fluorescein angiographic examination,
      were further studied with ICG videoangiography. RESULTS: On ICG videoangiographic
      examination, 9 of the 244 (4%) eyes had no evidence of underlying CNV, or
      essentially a pure serous PED. Each of the remaining 235 eyes (96%) had evidence
      of neovascularization and were defined as having a vascularized PED. These eyes
      were further divided into two groups, depending on the size and delineation of
      the neovascularization seen. Of the 235 eyes with vascularized PEDs, 89 (38%) had
      a solitary area of neovascularization that was well delineated, no more than one
      disc area in size, and defined as focal CNV. The other 146 (62%) eyes had a
      larger area of neovascularization, with variable delineation, defined as plaque
      CNV. Based on conventional guidelines, some patients were considered to be
      potentially eligible for laser photocoagulation treatment. CONCLUSION: The
      results of this study suggest that ICG videoangiography may be an important
      adjunct to the diagnosis, classification, and potential treatment of patients
      with AMD and occult CNV associated with a serous PED (vascularized PED).

PMID- 7518608
TI  - Experimental granulomatous alveolitis in rat. Effect of antigen manipulation,
      smoke exposure and route of administration.
AB  - When Sephadex beads (0.45mg/kg b.w) are instilled intratracheally into rats, a
      granulomatous alveolitis with giant cell formation and fibrosis occurs. Moreover,
      the events in the alveolar region are paralleled by an eosinophil-dominated
      peribronchitis/bronchiolitis and perivasculitis. Bronchoalveolar lavage (BAL)
      shows a very distinct feature with an early pronounced neutrophil increase,
      followed by an increase of eosinophils and lymphocytes. BAL findings returned to
      normal after 1-2 weeks, but tissue morphology showed persistent inflammation with
      large numbers of eosinophils and to a lesser degree mononuclear cells,
      peribronchially and perivascularly several weeks after the instillation.
      Fragmentation of the Sephadex beads by ultrasonication dramatically diminished
      the response, giving a transient neutrophil alveolitis, without eosinophils and
      with no granuloma formation. On the other hand, when the Sephadex dose was
      divided into three, given 10 days apart, a more pronounced fibrosing activity
      occurred, with mast cells appearing in the collagen rich granulomas. Finally,
      smoke exposure had a significant suppressive effect upon the response. The
      numbers of cells in the interstitium as well as in the peribronchial and
      perivascular tissue were markedly decreased in the smoke exposed group compared
      to the controls. This decrease was mainly due to decreased numbers of mononuclear
      cells, while the numbers of eosinophils remained unchanged.

PMID- 7518609
TI  - [Multiple keratocysts of the jaws: apropos of 3 cases].
AB  - Multiple keratocysts of the jaws are habitual in the nevoid basal cell carcinoma
      syndrome (Gorlin and Goltz. Syndrome). The authors report 3 cases of multiple
      keratocysts in a 28 year-old woman and in two men respectively ages of 27 and 21
      years. In the third case some anomalies in which calcification of the falx
      cerebri were noted and suggested the Gorlin's syndrome. The limits of this
      syndrome with multiple keratocysts of the jaws are discussed.

PMID- 7518610
TI  - Stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain
      immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at various
      conditions.
AB  - Urine samples from 10 randomly selected patients with advanced renal disease were
      each divided into six aliquots and a preservative solution containing
      benzamidinium chloride, EDTA, tris(hydroxymethyl)-aminomethane and azide was then
      added to three of the aliquots. Aliquots with and without additive were then
      stored at room temperature for up to 7 days, at 4 degrees C for up to 30 days and
      at -20 degrees C for up to 6 months. The concentrations of albumin, protein HC,
      IgG, orosomucoid and alpha 1-antitrypsin as well as the kappa- and lambda-chain
      immunoreactivities in the samples were determined by automated immunoturbidimetry
      or by single radial immunodiffusion after 1, 3, 7, 14, 30, 90 and 180 days of
      storage. All investigated proteins, except alpha 1-antitrypsin in native urine,
      were stable for 7 days in the samples stored at room temperature both in the
      presence and absence of additives. All investigated proteins, except alpha 1
      antitrypsin in native urine, were stable for 30 days in the samples stored at 4
      degrees C both in the presence and absence of additives. A more complex pattern
      was observed for the stability of the proteins in the frozen samples. The IgG
      level decreased rapidly in several samples stored without additives but not in
      samples stored with additives. The alpha 1-antitrypsin concentration decreased
      rapidly to about 50% of the initial value in several samples stored both with and
      without additives. The rate of the decrease for both the IgG and the alpha 1
      antitrypsin level varied between samples and the main decrease for several
      samples was seemingly caused by the freezing and/or thawing per se and not by the
      storage period in between.

PMID- 7518611
TI  - Serum alpha-fetoprotein and alcohol consumption.
AB  - Fifty-nine persons, 23 chronic alcoholics and 36 normal healthy persons with a
      well described alcohol consumption, had the serum concentration of alpha
      fetoprotein determined by a sensitive monoclonal immunofluorescent assay. A
      significant elevation in S-AFP was found in alcoholics, median 4.1 kIU/l as
      compared to 3.0 kIU/l in near-abstainers (< 12 g ethanol per day) (p < 0.02).
      This difference was not explained by differences in age. S-AFP correlated
      positively with age (p = 0.01). In non-alcoholics a borderline significant
      correlation with S-AFP was found with average daily alcohol consumption (self
      reported) (p = 0.09) and a significant correlation with the serum concentration
      of carbohydrate-deficient transferrin (S-CDT) (p = 0.004). In 11 alcoholics 2
      months of abstention from alcohol was accompanied by a median reduction of 21% in
      S-AFP (p < 10(-5)). In alcoholics, but not in social drinkers, S-AFP correlated
      with S-ASAT (p = 0.004). The increase of S-AFP with alcohol consumption may
      reflect reversible alcohol-induced liver affection.

PMID- 7518612
TI  - On the transfer of serum proteins to the rat intestinal juice.
AB  - The in vivo pattern of serum proteins in the rat small-intestinal juice was
      characterized by crossed immunoelectrophoresis. Immunoglobulins and albumin,
      alpha-1-antitrypsin, transferrin, and orosomucoid were present. Larger serum
      proteins were absent (ceruloplasmin, haptoglobin, alpha-1-macroglobulin, alpha
      and beta lipoproteins). Thus, apart from immunoglobulins, only serum proteins
      with a molecular mass less than approximately 100 kDa were demonstrated. The
      origin and epithelial transfer were further characterized, using albumin as a
      model. No sign of local synthesis of albumin by the enterocytes was found by
      Northern blotting, and no albumin was found in the Golgi complex by immunogold
      electron microscopy. By immunogold electron microscopy a heavy labelling of
      albumin was observed in the interstitial spaces between the villus enterocytes.
      Where the enterocytes disintegrated, albumin was seen to leak out into the
      intestinal lumen from the opened interstitial spaces. A weak labelling was also
      found in the lysosomal/endosomal-like structures, especially in the crypt
      enterocytes, indicating pinocytosis of albumin. We conclude that the main reason
      for the occurrence of certain serum proteins in the intestinal juice is a
      selective passage through the capillary wall followed by passive intercellular
      transport via delivery of the serum in the interstitial space during
      disintegration of the enterocytes.

PMID- 7518613
TI  - Serum collagen type IV for the assessment of fibrosis and resistance to
      interferon therapy in chronic hepatitis C.
AB  - Sixty-nine patients with chronic hepatitis C (CH-C) were treated with interferon
      therapy, and serum collagen type IV (s-collagen IV) levels were measured by
      enzyme immunoassay to analyze the responsiveness to interferon therapy.
      Classified by the improved pattern of serum alanine aminotransferase levels after
      interferon administration, 23 patients were judged as sustained responders, 23 as
      transient responders, and 23 as non-responders. Fibrotic grades of the liver
      sample correlated statistically with the levels of s-collagen IV (P < 0.01). Pre
      therapy s-collagen IV levels of sustained responders were significantly lower
      than those of the other responders, and only sustained responders showed a
      significant decrease of s-collagen IV levels after interferon therapy, in
      accordance with histologic improvement. Multivariate analysis showed that s
      collagen IV and hepatitis C virus genotype were the most important factors
      affecting the response to interferon therapy of all variates. Thus, s-collagen IV
      is one of the most useful aids for the evaluation of liver fibrotic grade in CH-C
      and a potent predicting indicator for the responsiveness to interferon therapy.

PMID- 7518614
TI  - Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity.
AB  - Two molecular mechanisms of T cell-mediated cytotoxicity, one perforin-based, the
      other Fas-based, have been demonstrated. To determine the extent of their
      contribution to T cell-mediated cytotoxicity, a range of effector cells from
      normal control or perforin-deficient mice were tested against a panel of target
      cells with various levels of Fas expression. All cytotoxicity observed was due to
      either of these mechanisms, and no third mechanism was detected. Thus, the
      perforin- and Fas-based mechanisms may account for all T cell-mediated
      cytotoxicity in short-term in vitro assays.

PMID- 7518615
TI  - Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking
      neuronal NOS.
AB  - Long-term potentiation (LTP) is a persistent increase in synaptic strength
      implicated in certain forms of learning and memory. In the CA1 region of the
      hippocampus, LTP is thought to involve the release of one or more retrograde
      messengers from the postsynaptic cell that act on the presynaptic terminal to
      enhance transmitter release. One candidate retrograde messenger is the membrane
      permeant gas nitric oxide (NO), which in the brain is released after activation
      of the neuronal-specific NO synthase isoform (nNOS). To assess the importance of
      NO in hippocampal synaptic plasticity, LTP was examined in mice where the gene
      encoding nNOS was disrupted by gene targeting. In nNOS- mice, LTP induced by weak
      intensity tetanic stimulation was normal except for a slight reduction in
      comparison to that in wild-type mice and was blocked by NOS inhibitors, just as
      it was in wild-type mice. Immunocytochemical studies indicate that in the nNOS-
      mice as in wild-type mice, the endothelial form of NOS (eNOS) is expressed in CA1
      neurons. These findings suggest that eNOS, rather than nNOS, generates NO within
      the postsynaptic cell during LTP.

PMID- 7518616
TI  - Specific interaction of type I receptors of the TGF-beta family with the
      immunophilin FKBP-12.
AB  - Transforming growth factor-beta (TGF-beta) family members bind to receptors that
      consist of heteromeric serine-threonine kinase subunits (type I and type II). In
      a yeast genetic screen, the immunophilin FKBP-12, a target of the macrolides
      FK506 and rapamycin, interacted with the type I receptor for TGF-beta and with
      other type I receptors. Deletion, point mutation, and co-immunoprecipitation
      studies further demonstrated the specificity of the interaction. Excess FK506
      competed with type I receptors for binding to FKBP-12, which suggests that these
      receptors share or overlap the macrolide binding site on FKBP-12, and therefore
      they may represent its natural ligand. The specific interaction between the type
      I receptors and FKBP-12 suggests that FKBP-12 may play a role in type I receptor
      mediated signaling.

PMID- 7518617
TI  - Melioidosis survey in Kenya.

PMID- 7518618
TI  - Urinary thromboxane and 6-keto-prostaglandin F1 alpha are early markers of acute
      rejection in experimental pancreas transplantation.

PMID- 7518619
TI  - Combined immunosuppressive therapy with low dose FK506 and antimetabolites in rat
      allogeneic heart transplantation.
AB  - Following rat heterotopic heart allotransplantation, low to lethal doses of the
      antimetabolites mizoribine (MIZ), RS-61443 (RS), and AZA were given alone or in
      combination with subtherapeutic doses of FK506 (0.04 mg/kg/day) for 14 days after
      transplantation. With the median effect analysis of Chou and Kahan for
      quantitative drug interactions, substantial therapeutic synergism was
      demonstrated between FK506 and non-toxic doses of MIZ (2.5, 5, and 10 mg/kg/day)
      or AZA (5, 30, and 45 mg/kg/day), which was particularly evident with the lowest
      dose MIZ (2.5 mg/kg/day). When FK506 was used in combination with MIZ or AZA but
      not with RS, the maximum effect (peak median graft survival) was enhanced
      significantly from 15 days (MIZ alone) to 26 days (P < 0.05), and from 19 days
      (AZA alone) to 32 days (P < 0.01). In contrast, RS interacted with FK506 no more
      than additively. Although RS was the most powerful single antimetabolite, the
      best overall survival was obtained by combining AZA and FK506. The addition of
      FK506 did not significantly increase the percent mortality and LD50 of the
      antimetabolites.

PMID- 7518620
TI  - Quantitative comparison of rapamycin and cyclosporine effects on cytokine gene
      expression studied by reverse transcriptase-competitive polymerase chain
      reaction.
AB  - We developed and applied a quantitative competitive polymerase chain reaction
      method to study the expression of various cytokine genes in Con A-stimulated
      murine splenocytes. This method relies on the use of competitive templates that
      differ from the target cytokine cDNA templates only by the introduction of a
      unique restriction endonuclease site in the center of each competitive template.
      After same-tube amplification using a single pair of oligonucleotide primers for
      both the target and competitive templates, restriction with the unique
      endonuclease yields 2 species that are readily resolved on agarose gel
      electrophoresis: full-length target and half-length competitor fragments. Using
      this method, we studied the time course and effects of CsA and rapamycin on IL-2,
      IFN-gamma, IL-4, and IL-10 gene expression following Con A stimulation. IL-2, IFN
      gamma, and IL-10 share a common pattern of gene expression peaking at
      approximately 6 hr, while IL-4 gene expression peaks later, at approximately 20
      hr. CsA very effectively inhibits expression of IL-2, IFN-gamma, and IL-4, but it
      inhibits IL-10 expression only 65%. Rapamycin inhibits IL-10 gene expression 100%
      and is less effective inhibiting the other cytokines. This pattern of inhibition
      is consistent with a calcium and protein kinase C independent pathway for IL-10
      gene regulation and supports the notion that CsA and rapamycin may be used
      together to advantage.

PMID- 7518621
TI  - Promoter of the mouse gene encoding calcium-independent nitric oxide synthase
      confers inducibility by interferon-gamma and bacterial lipopolysaccharide.
AB  - We have proved that iNOS is regulated by induction of transcription. The
      induction of iNOS mRNA requires synthesis of an intermediary protein(s) and
      probably involves action of a protein kinase or kinases. We have cloned and
      sequenced a 1.7-kilobase pair fragment from the 5'-flanking region of the iNOS
      gene and proved that this region contains a promoter which confers inducibility
      of iNOS by LPS and IFN-gamma.

PMID- 7518622
TI  - The effect of in vivo administration of recombinant methionyl human stem cell
      factor on the number of human marrow hematopoietic stem cells.

PMID- 7518623
TI  - Tyrosine phosphorylation defines a unique transduction pathway in human B cells
      mediated via CD40.

PMID- 7518626
TI  - Frequencies of neutrophil-specific antigens among Chinese in Taiwan.

PMID- 7518624
TI  - Localization of the genetic defect in X-linked immunoglobulin deficiency with
      normal or elevated IgM (HIGMX-1) to the CD40 ligand gene.

PMID- 7518625
TI  - Application of the MAIEA assay to the Kell blood group system.
AB  - The monoclonal antibody-specific immobilisation of erythrocyte antigens (MAIEA)
      test has been employed to investigate the Kell system using five monoclonal
      antibodies which recognise high frequency epitopes on the 93,000-molecular weight
      Kell glycoprotein: BRIC 18, BRIC 68, BRIC 107, BRIC 203 and 6-22. BRIC 107, which
      has anti-k-like (KEL2) specificity, identifies a distinct epitope, whilst
      competitive binding assays suggested that BRIC 203 (anti-Kpbc), BRIC 18, BRIC 68
      and 6-22 (anti K14) comprise an overlapping set of epitopes. The MAIEA assay has
      been very successful in confirming the assignment of most of the Kell and para
      Kell antigens to the Kell protein. Due to the competitive nature of the assay and
      the fact that the monoclonal antibodies bind to different regions, the results
      also suggest the relative positions of some of the Kell antigens on the Kell
      protein; these appear to be located in at least five spatially distinct regions.

PMID- 7518627
TI  - Vaccine potential of meningococcal FrpB: studies on surface exposure and
      functional attributes of common epitopes.
AB  - Neisseria meningitidis expresses several novel outer membrane proteins (OMPs) in
      vivo and when grown under iron limitation in vitro. One of the most prominent is
      a 70 kDa iron-regulated protein (FrpB). FrpB was purified by elution from SDS
      polyacrylamide gels and rabbit polyclonal antiserum (R-70) was raised against it.
      R-70 was bactericidal against homologous, but not heterologous, strains in the
      presence of human complement. The bactericidal activity was retained when R-70
      was adsorbed with formaldehyde-fixed iron-replete cells (i.e. not expressing
      FrpB), but lost when absorbed with fixed iron-restricted cells (which express
      FrpB). A murine monoclonal anti-FrpB antibody (mAb M70) was raised against a
      common epitope which showed complete cross-reaction on Western blots of OMPs from
      other serogroups and serotypes of N. meningitidis and some commensal Neisseriae
      species. However, it failed to kill the organism. Immunogold electron microscopy
      on ultrathin sections, using the R-70 antiserum adsorbed with fixed iron-replete
      cells, showed labelling on 40% of the cells, whereas the R-70 adsorbed with fixed
      iron-restricted cells and mAb M70 failed to label. However, none of these sera
      labelled whole cells, suggesting lack of surface accessibility. It appears that
      the highly conserved cross-reactive epitopes of FrpB only become exposed in the
      process of generating the antigen, whereas the surface-exposed epitopes
      recognized in killing assays are immunologically variable among different
      strains.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518629
TI  - Treatment of venous leg ulcers with topical iloprost: a placebo controlled study.
AB  - The disturbed microcirculation is seen as a causative factor in provoking venous
      leg ulcers. The stable prostacyclin analogue iloprost has shown beneficial
      effects on the disturbed microcirculation after intravenous infusions. In this
      study the topical route was chosen in order to facilitate handling and to reduce
      the possibility of systemic adverse reactions. The aim of this study was to
      assess the efficacy and tolerability of two concentrations of iloprost solutions
      (0.0005% and 0.002%). The trial design was a randomized, double-blind, placebo
      controlled study in 11 centres in Germany with 49 patients allocated to treatment
      1 (placebo solution); 49 patients to treatment 2 (0.0005% iloprost solution) and
      50 patients to treatment 3 (0.002% iloprost solution). The study solutions were
      applied twice weekly for a period of eight weeks on the ulcer edge and ulcer
      surrounding. This study failed to show any statistically significant reduction in
      the ulcer size as a result of the iloprost treatment compared to the placebo
      treatment. Possible reasons for the findings are discussed.

PMID- 7518630
TI  - [Uroflowmetry in the assessment of patients with benign prostatic hyperplasia].
AB  - Uroflowmetry is the most physiologic and non invasive assessing method of lower
      urinary tract obstruction: it proves to bring objective evidence of the prostatic
      blockage degree. We performed 1094 urinary flow tests in 264 patients with BPH,
      suffering from voiding problems; 188 males had undergone surgical treatment and
      86 medical therapy. These patients were examined again about 3 months after
      prostatectomy and about 3, 6, 9 months during pharmacologic treatment. Symptoms
      were valued according to international prostatic symptomatologic score (I-PSS).
      The assessment of residual urine was performed by bladder ultrasound. Among the
      264 patients, nocturia was present in 81.8%, weakness of stream in 75% and
      urgency in 47.7%. The average I-PSS for obstructed patients and postoperative
      were respectively 26 (21-32) and 5 (0-7). Frequency and weakness of stream were
      commonly (80% of cases) associated with a reduction in the maximum flow rate
      (Qmax). Qmax and average flow (Qave) improved after prostatectomy respectively
      from 7.1 ml/s to 18.9 ml/s and 4.1 ml/s to 8.3 ml/s. 6/264 males with normal Qmax
      and 132/264 with Qmax < 10 ml/s were shown to have residual urine > 80 ml. Among
      the uroflowmetry parameters analysed, the best correlation with the degree of
      prostatic obstruction degree is Qmax. Residual urine is a sign of an abnormality
      of bladder function rather than the direct result of urethral blockage.
      Uroflowmetry is a useful clinical tool in the diagnosis and follow-up of males
      with BPH.

PMID- 7518628
TI  - Analysis of the humoral response elicited in mice by a chimeric peptide
      representing variable segments I and IV of the major outer membrane protein of
      Chlamydia trachomatis.
AB  - A synthetic chimeric peptide representing the variable segments I (VS I) and IV
      of the major outer membrane protein (MOMP) of Chlamydia trachomatis, serovars C
      and E respectively, was studied to determine its ability to elicit a neutralizing
      humoral response in mice. Antibody responses varied to the peptide in the five
      inbred strains of mice, A/J(H-2a), DBA/1(H-2q), C57BL/10(H-2b), CBA/J(H-2k),
      Balb/c(H-2d), that were immunized. There was a spectrum of antibody responses
      which ranged from high ELISA and IFA titres by the C57BL/10 mice to little or no
      response by Balb/c mice. Antisera from C57BL/10 mice recognized all 15 serovars
      of C. trachomatis in a dot blot assay. A pepscan of the antisera from C57BL/10
      mice showed strong reactivity to both neutralizing epitopes VAGLQNDPT in VS I of
      serovar C and the species-conserved peptide, TLNPTIA, in the VS IV. This
      antiserum neutralized, in vitro, the infectivity of serovars representing the B
      complex (B, D and E), C complex (C and J), B-related (F) and C-related (L3)
      complexes. In an attempt to elicit a stronger response to the peptide in the
      weakly reactive Balb/c and the DBA/1 strains, the peptide was conjugated to the
      carrier, keyhole limpet haemocyanin (KLH). All mice immunized with the KLH
      peptide produced high-titred antisera that recognized neutralizing epitopes in VS
      I and VS IV and strongly neutralized the infectivity of both serovars C and E.

PMID- 7518632
TI  - T cell vaccination in multiple sclerosis: hopes and facts.
AB  - Six MS-patients were inoculated three times with autologous attenuated MBP
      specific T cell clones at two month intervals. No toxic effects were observed.
      After the third inoculation the precursor frequency of the MBP-specific T cells
      dropped to undetectable levels in all patients. Injection of attenuated MBP
      specific T cells gave rise to a pronounced response of anti-clonotypic T cells
      and a limited anti-ergotypic response. The anti-clonotypic T cells proliferated
      in the presence of the vaccine clones and were inhibitory and cytotoxic for the
      same vaccine clones. This clinical trial shows for the first time that antigen
      specific T cell vaccination in humans is feasible. The results obtained are
      highly promising for future treatments of Multiple Sclerosis and other autoimmune
      diseases.

PMID- 7518633
TI  - Auto-antibodies in neurological diseases.

PMID- 7518631
TI  - [The role of LH-RH analogue in benign prostatic hyperplasia].
AB  - In our study 7 patients considered high risk for any surgical and anesthetic
      intervention, with benign prostatic hyperplasia, whose 2 with permanent catheter,
      were treated for 6 months with luteinizing hormone-releasing hormone analogue.
      The treatment resulted in an average decrease in prostatic volume of 21.7%;
      reduced the serum PSA/PAP values of 52% and 43%, respectively; 4 pz improved
      their symptom score (1 pz removed the permanent catheter), 2pz kept stationary
      and 1 pz made worse. No particular side effects were presented and all patients
      finished the therapy. We conclude that LH-RH analogue therapy should be
      restricted to selected patients and then it will have to be continued for a long
      period of time.

PMID- 7518634
TI  - Oxygen or low concentrations of nitric oxide reverse pulmonary vasoconstriction
      induced by nitric oxide synthesis inhibition in rabbits.
AB  - The objective of this study was to investigate the role of nitric oxide and
      oxygen in the regulation of pulmonary vascular resistance, especially by means of
      substitution with nitric oxide after inhibition of endogenous nitric oxide
      formation. In artificially ventilated open-chest rabbits pulmonary vascular
      resistance at normoxic ventilation (FIO2 = 21%) was 56 +/- 6 cmH2O ml-1 min-1
      1000-1 (mRUL). N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg kg-1), an
      inhibitor of NO synthase, increased pulmonary vascular resistance to 122 +/- 17
      mRUL at normoxic ventilation. In response to L-NAME there was also an increase in
      mean arterial blood pressure. Exogenous nitric oxide (0.014-9 p.p.m. in the
      inhaled air) dose-dependently and reversibly counteracted the effect of L-NAME on
      pulmonary vascular resistance at normoxic ventilation, without affecting systemic
      blood pressure. In addition, the L-NAME-induced vasoconstriction was critically
      dependent on oxygen. Thus, during hypoxic ventilation (FIO2 = 10%) the pulmonary
      vascular resistance was increased approximately four-fold by the presence of L
      NAME (30 mg kg-1), and increments in FIO2 (21-100%) dose-dependently and
      reversibly counteracted the effect of L-NAME on pulmonary vascular resistance.
      Taken together these findings demonstrate that inhalation of low doses of NO may
      act as a replacement when endogenous NO synthesis is inhibited, and that
      pulmonary vasoconstriction induced by NO synthesis inhibition is likely to be the
      result of interference with oxygen-dependent regulatory mechanisms. Endogenous NO
      co-operates with oxygen to evoke a vasodilator component of the pulmonary hypoxic
      pressor response, balancing a hitherto unknown constrictor mechanism.

PMID- 7518635
TI  - Histamine release and its effects in ischaemia-reperfusion injury of the isolated
      rat heart.
AB  - Histamine is released from the heart during ischaemia-reperfusion injury. As
      histamine has cardiac effects, we investigated the role of histamine in ischaemia
      reperfusion injury of isolated rat hearts. A Langendorff-model with 30 min global
      (37 degrees C) ischaemia followed by 60 min reperfusion was employed. The effects
      of ischaemia alone (n = 10, group 1.1 + n = 10, group 2.1, 2 different series),
      and ischaemia with H1- and H2-receptor blockade with cimetidine (10 microM, n =
      10), chlorpheniramine (10 microM, n = 8), terfenadine (10 microM, n = 8), and
      promethazin (10 microM, n = 9), or both cimetidine and chlorpheniramine (n = 8),
      were studied. Histamine was measured in the coronary effluent and cardiac tissue
      of group 1.1. Release of histamine increased from 6.5 +/- 1 pmol min-1 before
      ischaemia to 19 +/- 3 pmol min-1 at the start of reperfusion. Ischaemia decreased
      left ventricular developed pressure to 18 +/- 11% (1.1) and 50 +/- 11% (2.1) of
      initial value (mean +/- SEM) at the start of reperfusion. Left ventricular end
      diastolic pressure increased from 0 to 79 +/- 8 mmHg (1.1) and 39 +/- 9 (2.1)
      mmHg, while left ventricular systolic pressure was unchanged (101 +/- 12% in 1.1
      and 101 +/- 10% in 2.1). Severe arrhythmias were induced in 90 (1.1) and 30
      (2.1)% of the hearts, while coronary flow decreased during reperfusion. H2
      blockade did not modify the changes in left ventricular pressures, coronary flow,
      or heart rate induced by ischaemia. Three different H1-blockers increased left
      ventricular systolic pressure, inhibited the decrease of developed pressure,
      attenuated the increase of end-diastolic pressure, and totally inhibited
      reperfusion arrhythmias. The effect of both blockers together was similar to that
      of H1-blockers alone. Coronary flow was increased during reperfusion in two of
      the groups with H1-blocker compared with ischaemic controls. Increased release of
      histamine from ischaemic-reperfused rat hearts concurred with depression of left
      ventricular function and arrhythmias during early reperfusion. Cardiac
      dysfunction during reperfusion was attenuated by three different H1-receptor
      blockers.

PMID- 7518636
TI  - Systemic N-nitro-L-arginine-ester (L-NAME), inhibitor of nitric oxide synthase,
      relieves chronic allodynia-like symptom in rats with spinal cord lesion.

PMID- 7518637
TI  - Influence of atropine on the depletion of vasoactive intestinal peptide,
      substance P and calcitonin gene-related peptide from rat parotid gland in
      response to parasympathetic nerve stimulation.

PMID- 7518639
TI  - The influence of Tolpa Peat Preparation (TPP) on rat liver regeneration.
AB  - The effect of Tolpa peat preparation (TPP) on the regenerative response has been
      examined in rats submitted to two thirds hepatectomy. The ornithine decarboxylase
      activity, spermidine and histamine levels, DNA and RNA content, RNA/DNA ratio and
      the mass of restituted liver were used to test the intensity of the regenerative
      processes. The action of TPP is dual: a short-term application of TPP at a dose
      of 20 mg/kg/day causes an inhibition of the ornithine decarboxylase activity, the
      decrease in spermidine formation, the levels of DNA and RNA, and liver
      restitution. The multiple application of TPP, on the other hand, results in a
      stimulation of ornithine decarboxylase, the increase in spermidine and histamine
      as well as RNA and DNA levels in regenerating liver; concomitantly, the liver
      mass tends to increase in TPP treated groups. TPP might exert its effects, at
      least partially, by interfering with polyamine biosynthesis.

PMID- 7518638
TI  - The effect of TPP, theophylline and theobromine on the angiogenic activity of
      mononuclear leucocytes obtained from diabetic patients with proliferative
      retinopathy.
AB  - Tolpa Peat Preparation (TPP) administered in various doses does not influence the
      ability of mononuclear cells (MNC) obtained from diabetic patients with
      proliferative retinopathy to induce neovascularization response in H-LIA test.
      Methylxanthines (theophylline, theobromine) significantly decrease the angiogenic
      activity of these cells. The therapeutic value of these drugs in proliferative
      retinopathy should be evaluated.

PMID- 7518640
TI  - [Relationship between serum PSA and prostate volume in benign hyperplasia].
AB  - PSA is, currently, the best marker to detect prostatic changes, although it
      looses specificity when used in the differential diagnosis of certain pathologies
      of the prostate gland. Forty-four patients with benign prostate hyperplasia were
      analyzed and 26 (59%) of them were found to have higher than normal PSA levels.
      An estimate was made of the degree of correlation between serum PSA and prostatic
      volume in the patients examined, so as to find a formula that could be useful to
      apply this marker in the differential diagnoses of prostate adenoma and hidden
      prostate cancer. No linear relationship was found between prostate volume with
      benign hyperplasia and PSA (R = 0.13). This lack of relationship in a high
      percentage of patients with prostate adenoma induces to turn unnecessary to
      histopathological confirmation in order to rule out prostate cancer.

PMID- 7518641
TI  - Lymphomagenesis in AKR mice: B cell lymphomas as a model of tumor dormancy.

PMID- 7518642
TI  - Localization of pulmonary nodules before thoracoscopic surgery: value of
      percutaneous staining with methylene blue.
AB  - OBJECTIVE: Video-assisted thoracic surgery (VATS) is a new procedure that makes
      it possible to see the intrathoracic organs and to resect pulmonary nodules
      without thoracotomy. Preoperative localization of small nodules that may not be
      visible or palpable during VATS is desirable. Percutaneous placement of spring
      hookwires is widely used to localize pulmonary nodules before VATS; infrequently,
      the adjacent lung parenchyma is also stained with methylene blue. The purpose of
      this study was to evaluate the effectiveness of methylene blue staining of
      pulmonary nodules without placement of a hookwire. SUBJECTS AND METHODS: Fifteen
      pulmonary nodules in 15 patients were localized preoperatively under CT guidance
      by using techniques identical to those for CT-guided fine-needle aspiration of
      pulmonary nodules. Approximately 0.3 ml of methylene blue dye was injected into
      the nodule with a 22-gauge Chiba needle to stain the nodule, the needle pathway,
      and the visceral pleura. In two patients, a hookwire also was placed. All
      patients had solitary nodules in which transbronchial or transthoracic biopsy had
      been unsuccessful. The mean nodule diameter was 16 mm (range, 8-33 mm), and the
      mean distance to the nearest pleural surface was 10 mm (range, 0-21 mm). The
      localization procedure required a mean of 32 min (range, 18-47 min). RESULTS: All
      15 nodules were stained successfully either in the center or within the margins;
      the two hookwires were found to be displaced. In three cases, pulmonary
      hemorrhage occurred as a complication of the percutaneous staining procedure: in
      one case, subsequent conversion to thoracotomy was necessary owing to pulmonary
      hemorrhage and additional pleural bleeding during VATS, which resulted from
      puncture with a trocar directly into the pleural adhesions. Anticipated
      complications, such as pneumothorax, occurred in five patients; one patient had
      pleuritic pain, but none required treatment. In one patient, conversion to
      thoracotomy was done so that an adenocarcinoma could be treated by means of a
      lobectomy. In two others, thoracotomy was done because of problems with technical
      devices. CONCLUSIONS: Percutaneous staining of pulmonary nodules is an accurate
      technique for localizing nodules before VATS. The procedure is easily and safely
      performed, and it obviates wire-related complications, such as severe pleuritic
      pain.

PMID- 7518643
TI  - Choroid plexus-ventricular wall separation in fetuses with normal-sized cerebral
      ventricles at sonography: postnatal outcome.
AB  - OBJECTIVE: The choroid plexus typically fills the atrium of the lateral
      ventricles of the brain in normal fetuses, but separates from the medial
      ventricular wall with increasing ventriculomegaly. Sonographic depiction of
      choroid plexus-ventricular wall separation has been associated with a high
      frequency of unfavorable outcomes in fetuses with mild ventricular dilatation.
      This separation, however, is also observed in a small subgroup of fetuses with
      normal ventricular measurements. The objective of this study was to ascertain the
      prognosis for fetuses when choroid plexus-ventricular wall separation and normal
      sized lateral ventricles are seen on antenatal sonograms. MATERIALS AND METHODS:
      Postnatal follow-up was reviewed for 74 fetuses showing a 3 mm or greater
      separation between the choroid plexus and the medial ventricular wall and normal
      sized (< or = 10 mm) ventricles on antenatal sonograms. Fetuses were divided into
      normal and abnormal outcome groups, and the data were analyzed to determine if
      the amount of separation, the ventricular atrial diameter, or the evolution of
      these findings on follow-up sonograms was predictive of outcome. RESULTS: Fifty
      nine patients (80%) had normal outcomes (defined as no congenital anomalies and
      no significant subsequent medical history apart from usual infant and childhood
      illnesses) and 15 patients (20%) had abnormal outcomes. The severity of the
      abnormalities varied widely, ranging from relatively inconsequential, such as
      isolated polydactyly, to complex congenital malformation syndromes resulting in
      neonatal death. No consistent pattern of malformation was evident. Although we
      found a statistically significant difference in the degree of choroid plexus
      ventricular wall separation when fetuses were separated into normal and abnormal
      outcome groups, the range of measurements obtained in these two populations
      overlapped considerably. Outcomes were normal in all 13 patients in whom the
      choroid plexus-ventricular wall separation had returned to normal by the time of
      the last antenatal sonogram. CONCLUSION: A separation of 3 mm or greater between
      the choroid plexus and the medial ventricular wall is an important finding that
      is associated with an increased risk of an abnormal outcome even in the
      subpopulation of fetuses with normal-sized ventricles. Although the outcome will
      be normal in the majority (80%) of such fetuses, identification of choroid plexus
      ventricular wall separation mandates a meticulous examination of fetal anatomy.

PMID- 7518644
TI  - The interferons--Part 1.

PMID- 7518645
TI  - The associations of levels of serum potassium and magnesium with ventricular
      premature complexes (the Framingham Heart Study).
AB  - There are conflicting data regarding the impact of serum potassium and magnesium
      levels on susceptibility to ventricular premature complexes (VPCs) in the
      clinical setting. The associations of serum potassium and magnesium levels with
      the prevalence of complex or frequent (> 30/hour, multiform or repetitive) VPCs
      were examined after adjusting for age, sex, smoking, caffeinated coffee
      consumption, alcohol consumption, and left ventricular mass in Framingham
      Offspring Study subjects who were free of clinically apparent heart disease.
      There were 3,327 eligible subjects (mean age 44 years). Complex or frequent VPCs
      were present in 183 subjects (5.5%). When age-adjusted prevalences of complex or
      frequent VPCs were compared among quartiles of serum potassium and magnesium
      using a trend test, lower potassium (p = 0.002) and lower magnesium (p = 0.010)
      levels were associated with higher prevalence rates of arrhythmia. In logistic
      regression analyses that included potassium and magnesium simultaneously,
      potassium (p = 0.0021) and magnesium (p = 0.0311) levels were inversely
      associated with the occurrence of complex or frequent VPCs after adjustment for
      age, sex, smoking, coffee and alcohol consumption, diuretic use, and systolic
      blood pressure. These associations remained significant after accounting for left
      ventricular mass. A 1 SD decrement in potassium (0.48 mEq/liter) or magnesium
      (0.16 mEq/liter) level was associated with a 27% (95% confidence interval 6% to
      51%) and a 20% (95% confidence interval 3% to 41%) greater odds of complex or
      frequent VPCs, respectively. Lower levels of serum potassium and magnesium were
      concurrently associated with higher prevalence rates of ventricular arrhythmias.

PMID- 7518646
TI  - Effect of propranolol versus no antiarrhythmic drug on sudden cardiac death,
      total cardiac death, and total death in patients > or = 62 years of age with
      heart disease, complex ventricular arrhythmias, and left ventricular ejection
      fraction > or = 40%.

PMID- 7518647
TI  - Duration of Holter monitoring.

PMID- 7518648
TI  - The usefulness of human placental lactogen and keratin immunohistochemistry in
      the assessment of tissue from purported intrauterine pregnancies.
AB  - This study compared conventional light microscopy with immunohistochemistry in
      the histopathologic diagnosis of intrauterine pregnancy in curettings in which
      fetal parts and chorionic villi were absent. Hematoxylin and eosin-stained
      sections of the curettings, which were from 50 consecutive patients in whom
      incomplete abortion had been diagnosed clinically, were circulated to four
      pathologists who graded their diagnoses with a confidence score.
      Immunohistochemical examination using a standard streptavidin-biotin-peroxidase
      method with anti-HPL and antikeratin antisera was performed. The pathologists in
      the maternity hospitals achieved a high level of diagnostic confidence compared
      with those working in the general hospitals. However, there were erroneous
      diagnoses by the one pathologist in the former group and none by the latter.
      Critical path analysis showed that the best performing pathologist could
      accurately diagnose all but two of the cases that had been diagnosed with a
      degree of doubt by the other pathologists without recourse to immunohistochemical
      examination. These results suggest that immunohistochemistry may be used
      discriminately in uncertain cases or if relatively inexperienced pathologists are
      reporting.

PMID- 7518649
TI  - Relationship of burst-forming-unit-erythroid progenitors and their DNA-synthesis
      stage to fetal hemoglobin levels in hydroxyurea-treated patients with sickle cell
      anemia.
AB  - DNA-synthesis stage and total number of circulating burst-forming-units-erythroid
      (BFU-E) have been inversely correlated with hemoglobin F levels in the peripheral
      blood, as well as in the cells from the BFU-E-derived colonies obtained from
      homozygous sickle cell anemia (SS) patients during steady state. Similar studies
      in SS patients treated with cytotoxic agents have not been reported. However,
      regeneration of the erythroid marrow that follows the cytoreduction phase of
      chemotherapy has been suggested as one of the mechanisms of stimulation of fetal
      hemoglobin synthesis. Therefore, a longitudinal study of hemopoiesis in
      hydroxyurea-treated SS patients was conducted. Thirty-two sets of hemopoietic
      studies, including total circulating BFU-E and S-phase BFU-E, were obtained from
      three patients treated with hydroxyurea. A dose-dependent decrease in total BFU-E
      colonies occurred in peripheral blood of all three patients (r = -0.58, -0.85,
      and -0.97, respectively, with each P < 0.05). There was a strong positive
      correlation between hydroxyurea dose and fetal hemoglobin levels in two of the
      three patients who responded clinically (r = 0.89618 and 0.88632, respectively,
      with each P < 0.01). When data from all patients were combined (n = 32), there
      was a strong, inverse, linear relationship between total number of BFU-E and
      percentage S-phase BFU-E with fetal hemoglobin levels (r = -0.6649 and -0.7404,
      respectively, with each P < 0.0001). A stronger, curvilinear, multiple
      relationship was detected between total BFU-E and percentage S-phase BFU-E with
      fetal hemoglobin levels (R = 0.8351 and 0.8602 with each P < 0.0001).

PMID- 7518650
TI  - Criteria for use of interferon alfa-2a or interferon alfa-2b for selected
      indications in adults.

PMID- 7518651
TI  - Inflammatory mechanisms in Alzheimer's disease: implications for therapy.
AB  - OBJECTIVE: The purpose of this article is to review evidence that inflammatory
      and immune mechanisms are important in the pathophysiology of Alzheimer's disease
      and to suggest new treatment strategies. METHOD: The authors review the English
      language literature of the last 10 years pertaining to the pathophysiology of
      Alzheimer's disease. RESULTS: There is ample evidence supporting the hypothesis
      that inflammatory and immune mechanisms are involved in tissue destruction in
      Alzheimer's disease. Acute phase proteins are elevated in the serum and are
      deposited in amyloid plaques, activated microglial cells that stain for
      inflammatory cytokines accumulate around senile plaques, and complement
      components including the membrane attack complex are present around dystrophic
      neurites and neurofibrillary tangles. CONCLUSIONS: Clinical trials of anti
      inflammatory/immunosuppressive drugs are necessary to determine whether
      alteration of these inflammatory mechanisms can slow the progression of
      Alzheimer's disease.

PMID- 7518652
TI  - Expression of CD34 by solitary fibrous tumors of the pleura, mediastinum, and
      lung.
AB  - Solitary fibrous tumors are rare neoplasms that most commonly involve the pleura,
      mediastinum, and lung. Because they lack distinctive histologic features,
      immunologic staining has frequently been employed to exclude other neoplasms in
      the differential diagnosis. Their reported phenotype to date is generally
      negative, notably for muscle-type actins, desmin, keratin, and S-100 protein.
      Although this testing is of some help, it does not serve to distinguish all
      processes in the differential diagnosis, and when it does, it places too great an
      emphasis on a negative finding to make a diagnosis. We report here that CD34
      monoclonal antibodies reacted with 11 of 14 solitary fibrous tumors in paraffin
      sections. Thus, they provide a positive marker that distinguishes the solitary
      fibrous tumor from most elements in the differential diagnosis.

PMID- 7518653
TI  - [Placental hemangiomas].
AB  - In the following article the author describes 7 cases of hemangioma placentae
      observed for a period of 5 years and short characteristics of each of them are
      made. Quite detailed is discussed the problem about the clinical effects of this
      tumor-complications during pregnancy as well as to the fetus and the new-born
      child. Special attention is paid to the contradictory question about the
      hemangioma placentae and the maternal serum alpha-fetoprotein and their possible
      connection with the preeclampsia.

PMID- 7518654
TI  - In vitro effects of H1-antihistamines on histamine and PGD2 release from mast
      cells of human lung, tonsil, and skin.
AB  - Mast cells from different anatomic sites differ in cytochemistry and response to
      various secretory stimuli. We have investigated whether responsiveness to the
      second-generation H1-receptor antagonists, which are important first-line drugs
      for the relief of symptoms in patients with chronic urticaria and allergic
      rhinoconjunctivitis, also differs according to the site of origin of mast cells.
      The effects of terfenadine, ketotifen, and cetirizine were therefore examined in
      relation to the IgE-dependent release of histamine and prostaglandin D2 (PGD2)
      from dispersed human lung, tonsil, and skin mast cells. Terfenadine had a
      biphasic effect on lung and skin mast cells: at low concentrations, a
      concentration-dependent inhibition of histamine release from lung and skin mast
      cells was observed, whereas at higher concentrations the drug stimulated mediator
      release. Even at a high concentration, terfenadine inhibited mediator release
      from tonsil mast cells. Ketotifen had low potency as an inhibitor of mediator
      release from lung and tonsil mast cells. In skin mast cells, no inhibition of
      mediator release was observed below 1.0 microM, and above that concentration it
      induced mediator release. Cetirizine, a much less lipophilic drug than the others
      tested, did not induce mediator release from mast cells even at concentrations up
      to 100 microM. This drug showed concentration-dependent inhibition of IgE
      dependent mediator release from lung and tonsil mast cells only. Our results show
      that human mast cells are heterogeneous with respect to modulation of mediator
      release by these H1-antihistamines. In particular, differences were observed
      between skin mast cells and those dispersed from lung and tonsils.

PMID- 7518655
TI  - IgE and IgG cross-reactivity among Lol p I and Lol p II/III. Identification of
      the C-termini of Lol p I, II, and III as cross-reactive structures.
AB  - In this study, the homologous C-termini of Lol p I, Lol p II, and Lol p III were
      shown to contain cross-reactive B-cell epitopes. This was demonstrated by
      inhibition studies with purified Lol p I, II, and III and synthetic peptides of
      their C-termini. It was ruled out that the observed cross-reactivity was caused
      by cross-contamination of the purified allergens. Both human IgE and IgG bound to
      the C-terminus of Lol p I. These antibodies were cross-reactive with Lol p II
      and, more specifically, with its C-terminus. Within a small panel of allergic
      patients, no cross-reactivity with Lol p III was found. A hyperimmune polyclonal
      rabbit antiserum against Lol p I also recognized the Lol p I C-terminus. As for
      human antibodies, cross-reactivity with Lol p II and its C-terminus was
      demonstrated. Cross-reactivity with Lol p III was demonstrated with C-terminal
      peptides, but not with native Lol p III. A polyclonal rabbit antiserum against
      Lol p II bound to the C-terminal peptides of both Lol p II and III. This binding
      was inhibited with Lol p I, confirming that cross-reactive structures exist not
      only on the C-termini of Lol p II and Lol p I, but also of Lol p III and Lol p I.
      The existence of cross-reactivity between Lol p I and Lol p II and III possibly
      contributes to the frequently observed cosensitization for these allergens in
      grass-pollen-allergic patients.

PMID- 7518657
TI  - Decreased levothyroxine requirement in women with hypothyroidism during androgen
      therapy for breast cancer.
AB  - OBJECTIVE: To determine the effects of androgen administration on measures of
      thyroid function and thyroid hormone replacement doses in women with breast
      cancer. DESIGN: Consecutive patients with metastatic, hormone-dependent breast
      cancer who were eligible for androgen treatment. INTERVENTIONS: Androgen therapy
      (fluoxymesterone, 10 mg orally twice daily) was continued for as long as it was
      effective in controlling tumor growth. PATIENTS: 7 patients with no known thyroid
      disease and 4 others receiving long-term treatment for hypothyroidism.
      MEASUREMENTS: Serum levels of total and free thyroxine (T4), thyroid-stimulating
      hormone (TSH), and T4-binding globulin were determined before and every 4 weeks
      after androgen therapy was initiated. RESULTS: Within 4 weeks of androgen
      administration to the seven patients without thyroid disease, serum levels of
      total T4 and T4-binding globulin decreased (P < 0.001), whereas the calculated
      free thyroxine index and measured free hormone levels remained unchanged. Six to
      12 weeks after androgen therapy was discontinued, all seven patients remained
      clinically euthyroid, and serum levels returned to baseline values. In contrast,
      clinical hyperthyroidism developed shortly after androgen was administered to
      four patients who received long-term thyroid hormone replacement therapy. Within
      4 weeks of treatment, the serum free T4 level increased in each of the four
      patients, whereas the TSH level decreased. Thyroid hormone doses had to be
      reduced by 25% to 50% to maintain euthyroidism. CONCLUSIONS: The study documents
      the reversible effects of androgens on thyroid hormone levels and indicates the
      need to reduce thyroid replacement doses in women during androgen therapy.
      Monitoring thyroid hormone levels in patients receiving replacement therapy and
      perhaps in those with autonomous thyroid function is necessary after androgen
      therapy.

PMID- 7518656
TI  - Apple allergy: the IgE-binding potency of apple strains is related to the
      occurrence of the 18-kDa allergen.
AB  - Low-temperature, acetone powder extracts were prepared from mature fruit of 16
      apple strains. SDS-PAGE and immunoblot analysis revealed great variation in the
      relative amounts of the 18-kDa apple allergen in these extracts. EAST (RAST)
      scores, measured with individual and pool sera from patients allergic to birch
      pollen and apples, ranged from 0.2 to 4.0 and were related to the relative amount
      of the 18-kDa protein. These findings were confirmed by ELISA-inhibition assays,
      dose-related histamine release, semiquantitative evaluation of immunoblots by
      absorption/reflection densitometry, and skin prick tests with extracts of Golden
      Delicious, Boskoop, and Jamba apples (corresponding to a high, low, and very low
      18-kDa allergen content). Additional open oral challenge tests were performed
      with two apple-allergic patients and 15 and 16 apple strains. With all methods,
      the deduced allergenic potency decreased in the following order: Golden Delicious
      > Boskoop > Jamba. Therefore, we concluded that the IgE-binding potency of apple
      strains depends on the occurrence of the 18-kDa allergen.

PMID- 7518658
TI  - Didanosine resistance in HIV-infected patients switched from zidovudine to
      didanosine monotherapy.
AB  - OBJECTIVE: To determine the frequency and pattern of development of specific drug
      resistance mutations for human immunodeficiency virus (HIV) reverse transcriptase
      in patients switched from zidovudine to didanosine therapy and to examine the
      relation of the didanosine resistance mutation at codon 74 of the HIV reverse
      transcriptase gene to CD4+ T-cell changes and virus burden. DESIGN: Retrospective
      analysis of all patients enrolled at Stanford University in protocols where
      patients were switched from zidovudine to didanosine monotherapy. SETTING: A
      university hospital. PATIENTS: 64 patients infected with HIV who were switched
      from zidovudine to didanosine monotherapy. Patients had the acquired
      immunodeficiency syndrome (AIDS), AIDS-related complex, or were asymptomatic
      (mean [+/- SD] starting CD4+ T-cell count of 129 +/- 88 cells/mm3). MEASUREMENTS:
      Serial serum specimens were tested for the didanosine resistance mutation at
      codon 74 of the HIV reverse-transcriptase gene and for a zidovudine resistance
      mutation at codon 215 using selective polymerase chain reactions (PCR). Serum HIV
      RNA levels were determined by quantitative PCR. CD4+ T-cell counts were
      determined at serial time points. RESULTS: By 24 weeks of didanosine therapy, the
      proportion of patients with the didanosine resistance mutation at codon 74
      increased from 0% to 56% (36 of 64). In contrast, the proportion of patients with
      the zidovudine resistance mutation at codon 215 decreased from 84% at the start
      to 59% after 24 weeks of didanosine therapy (a 25% decrease, 95% lower CI, 15%; P
      < 0.0001). Patients who developed the codon 74 mutation had a greater decrease in
      CD4+ T cells after the development of the mutation than did patients without the
      mutation (P < 0.001). In addition, after 24 weeks of didanosine, patients who
      developed the codon 74 mutation had a greater serum HIV RNA burden than patients
      who remained wild type (did not have the mutation) at codon 74 (225,000 compared
      with 82,400 HIV RNA copies/mL serum; P = 0.01). CONCLUSIONS: Among patients
      infected with HIV who had advanced disease and were switched from zidovudine to
      didanosine therapy, more than one half developed the didanosine resistance
      mutation at codon 74 by 24 weeks of didanosine therapy. Patients who developed
      the codon 74 mutation had a greater decline in CD4+ T cells after the development
      of the mutation and had a greater serum virus burden than did patients without
      the codon 74 mutation.

PMID- 7518660
TI  - [Tumor angiogenesis in breast cancer: significance of vessel density as a
      prognostic indicator].
AB  - Clinical usefulness, particularly significance as a prognostic indicator, of
      tumor angiogenesis, was investigated in primary breast cancer patients.
      Angiogenesis was evaluated by an immunostaining to factor VIII antigen, which is
      an endothelial marker. Out of 220 primary breast cancer patients, 54 were
      included in the high vessel density group with over 100 counts of factor VIII
      positive cells/x200 microscopic field. The relapse-free survival rate of the high
      vessel density group was significantly worse than that of the low vessel density
      group with less than 100 vessel counts (p < 0.01). A multivariate analysis
      demonstrated that vessel density is an independent prognostic indicator as potent
      as nodal status. It was concluded that tumor angiogenesis is a new and potent
      prognostic indicator in primary breast cancer patients.

PMID- 7518659
TI  - Treatment of hyperthyroid disease.
AB  - PURPOSE: To evaluate treatments for hyperthyroid disease. DATA SOURCES: Selected
      studies published during the last 20 years addressing the diagnosis, causes, and
      treatment of hyperthyroid disease. STUDY SELECTION: Studies were chosen based on
      their usefulness in addressing specific points in the treatment of hyperthyroid
      disease. DATA EXTRACTION: Various treatment principles extracted from the
      references form the basis for the conclusions and recommendations made here.
      RESULTS: Hyperthyroid disease is a common endocrine disease. Although Graves
      disease is the most common cause of thyrotoxicosis, other primary and secondary
      causes exist. With classic signs and symptoms accompanied by confirmatory
      laboratory measures of thyroid hyperfunction, the diagnosis can be established
      firmly. Radioiodine is the preferred method to treat Graves disease; however,
      recent data concerning treatment with a combination of propylthiouracil and
      thyroxine require further evaluation to establish its efficacy. Radioiodine is
      also the preferred treatment for the other forms of hyperthyroid disease;
      however, patient-specific considerations in both may require patient-tailored
      therapies. CONCLUSIONS: Hyperthyroid disease can be treated definitively for most
      patients. Palliative therapy with beta-adrenergic blockade is useful in some
      patients. Further studies are needed to determine whether more recently described
      treatments have improved efficacy and whether therapy directed specifically at
      the underlying immunologic cause of Graves disease can be used successfully.

PMID- 7518661
TI  - [Treatment strategy to obtain cure for recurrent advanced breast cancer].
AB  - The three-year survival rate of a total of 186 patients with recurrent advanced
      breast cancer was 86% for complete responders, 27% for partial responders, and
      29% for patients remaining in stable diseases, respectively, at our two
      institutions. Thus, the results indicated that a complete response is the first
      step for long-term survival. High-dose chemotherapy with autologous stem cell
      support was administered after 4 cycles of induction chemotherapy. The results
      showed 12 complete response (60%) out of 20 patients, and 5 cases survived with
      no evidences of disease for 5-31 months. Both taxol and taxotere achieved
      response rates exceeding 50% in phase II trials on advanced breast cancer and
      therefore were expected to have a role in combination regimens with other drugs.

PMID- 7518663
TI  - Increased IgA antibodies to cytokeratins in the spondyloarthropathies.
AB  - OBJECTIVES: Increased levels of IgA antibodies to cytokeratin-18 (CK-18) and
      epidermal keratins (EpK) in the sera of patients with rheumatoid arthritis (RA)
      have been demonstrated previously. In the present study investigations were
      carried out to determine whether levels of these autoantibodies were also raised
      in the spondyloarthropathies, and whether there was any association with
      particular disease manifestations. METHODS: Using specific enzyme linked
      immunosorbent assays (ELISA) measurements were taken of IgA, IgG and IgM
      antibodies to EpK and to CK-18 in the sera of patients with psoriatic
      arthropathy, ankylosing spondylitis (AS), Reiter's syndrome, psoriasis and in
      normal subjects. RESULTS: IgA antibodies to both EpK and CK-18 were significantly
      increased in sera from patients with psoriasis and psoriatic arthropathy but not
      in the sera from the patients with AS or Reiter's syndrome, or in the controls.
      In psoriatic arthritis, however, these levels were significantly higher only in
      those patients with peripheral joint disease and not in those with axial
      arthritis alone. There was no significant increase in antibody levels in patients
      with AS or Reiter's syndrome. There were no differences in the levels of IgG or
      IgM antibodies to CK-18 or EpK between the patient groups and controls.
      CONCLUSIONS: Raised levels of IgA antibodies to CK-18 and EpK in psoriatic
      arthropathy and psoriasis probably reflect exposure of intracellular cytokeratin
      antigens to the immune system after damage to cytokeratin containing cells, and
      suggests a common pathogenic mechanism in these conditions which involves
      production of cytokeratin autoantibodies. In patients with psoriatic arthropathy,
      such a mechanism appears only to be operating in patients with peripheral joint
      involvement and not in those with axial arthritis.

PMID- 7518662
TI  - Low molecular weight IgM and CD5 B lymphocytes in rheumatoid arthritis.
AB  - OBJECTIVES: To evaluate the role of low molecular weight (LMW) IgM and CD5 B
      cells in rheumatoid arthritis (RA) and to explore the possibility that LMW IgM is
      derived selectively from this subset of B cells. METHODS: LMW IgM in sera and
      culture supernatants was detected by a sensitive immunoblot technique with an
      enhanced chemiluminescence detection system. CD5 B cells were determined by
      FACScan cytometry. In vitro studies were established in culture plates containing
      pokeweed mitogen with or without 2-mercaptoethanol (2-ME). Supernatants were
      obtained from CD5 positive hybridomas and CD5 negative hybridomas. Other
      immunological indices were measured by laser nephelometry. RESULTS: Circulating
      LMW IgM was detected in all rheumatoid patients with significantly higher levels
      being observed in sero-positive patients. LMW IgM correlated significantly with
      total IgM and RF. Peripheral blood mononuclear cells (PBMC) from the majority of
      the patients with RA secreted LMW IgM in vitro as did mononuclear cells from a
      synovial fluid sample. The addition of low concentrations of 2-ME to the culture
      medium enhanced the proportions of secreted monomeric IgM. In contrast, PBMC from
      healthy subjects secreted only trace quantities of LMW IgM. In RA no significant
      correlations were observed between CD5 B cells and LMW IgM and RF. LMW IgM could
      be detected in the supernatants from both CD5+ and CD5- B cell lines. Finally,
      CD5 B cells were not significantly elevated in RA and levels remained constant
      over time. CONCLUSION: LMW IgM exists in high concentrations in RA sera and
      synovial fluid. Serum level correlates with RF and IgM. In vitro studies have
      suggested that the occurrence of LMW IgM may be due to an intrinsic defect(s) in
      the assembly of the IgM pentameric molecule. LMW IgM is unlikely to be derived
      solely from CD5 B cells.

PMID- 7518664
TI  - Interleukin-6, acute phase reactants and clinical status in ankylosing
      spondylitis.

PMID- 7518665
TI  - Effects of aprotinin on acute recovery of cerebral metabolism in piglets after
      hypothermic circulatory arrest.
AB  - Brain protection during cardiopulmonary bypass and hypothermic circulatory arrest
      is incomplete. Activation of blood protease cascades may contribute to cellular
      injury under these conditions. To test this hypothesis, effects of the protease
      inhibitor aprotinin on recovery of brain energy metabolism after hypothermic
      circulatory arrest were studied in the piglet. Twenty-four 4-week-old piglets (10
      aprotinin-treated and 14 control) underwent core cooling, 1 hour of circulatory
      arrest at 15 degrees C, reperfusion and rewarming (45 minutes), and normothermic
      perfusion (3 hours) on cardiopulmonary bypass. Cerebral high-energy phosphate
      concentration and intracellular pH were studied by phosphorus-31 magnetic
      resonance spectroscopy in 12 animals. In the remaining animals cerebral and
      regional blood flow were measured with radioactive microspheres and carotid
      artery blood flow was measured with an electromagnetic flowmeter. Cerebral oxygen
      and glucose extraction were measured, and vascular resistance responses to
      endothelium-dependent (acetylcholine) and -independent (nitroglycerin)
      vasodilators were calculated. Recovery of cerebral adenosine triphosphate (p =
      0.02) and intracellular pH (p = 0.04) in the initial 30 minutes of reperfusion
      was accelerated in the aprotinin-treated piglets. These piglets showed a greater
      in vivo cerebral and systemic endothelium-mediated vasodilation (acetylcholine
      response: cerebral p < 0.01, systemic p = 0.04) after reperfusion. The response
      to endothelium-independent vasodilation (nitroglycerin) was the same in both
      groups. Carotid blood flow tended to be greater at 20 minutes of reperfusion and
      less during 45 to 80 minutes after reperfusion in the aprotinin-treated animals.
      Brain water content postoperatively was 0.8077 in the aprotinin group and 0.8122
      in control animals (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518666
TI  - Aggressive multimodality therapy for malignant pleural mesothelioma.
AB  - Nineteen patients with clinical stage I malignant pleural mesothelioma were
      treated with aggressive multimodality therapy. Nine patients underwent
      pleurectomy and decortication followed by immediate intrapleural chemotherapy
      with cisplatin and mitomycin C. Ten patients required pleuropneumonectomy
      followed within 1 week to 2 weeks by intrapleural administration of cisplatin
      (100 mg). Four to 8 weeks after operation, 15 patients underwent postoperative
      adjuvant cisplatin-based systemic chemotherapy. There were three postoperative
      complications (16%) requiring reoperation and one postoperative death (5%).
      Intrapleural chemotherapy was well tolerated with no complications. Systemic
      chemotherapy was poorly tolerated, and there was one chemotherapy-related death.
      Sixteen patients (84%) experienced good to excellent palliation. Three patients
      are currently alive with no evidence of recurrent disease at 10, 35, and 43
      months. The median overall survival was 13 months and the median disease-free
      survival, 11 months. Overall and disease-free 3-year survivals were 17% and 22%,
      respectively. Patients with epithelial malignant pleural mesothelioma had
      significantly better overall survival (p = 0.037) and disease-free survival (p =
      0.02) than patients with sarcomatous or biphasic malignant pleural mesothelioma.
      We conclude that despite major toxicity, in select patients with clinical stage I
      malignant pleural mesothelioma, aggressive multimodality therapy offers effective
      palliation and occasional long-term disease-free survival.

PMID- 7518667
TI  - Posterior mediastinal endodermal sinus (yolk sac) tumor in a female patient.
AB  - Primary endodermal sinus tumor (yolk sac tumor) of the mediastinum is uncommon.
      Most patients are young and male, and the great majority of tumors are found in
      the anterior mediastinum. We report a case of primary posterior mediastinal
      endodermal sinus tumor occurring in a female patient. Surgical excision was
      performed and three courses of combination chemotherapy were subsequently given.
      The serum alpha-fetoprotein level returned to normal.

PMID- 7518668
TI  - [Isolation and investigation of Staphylococcus aureus strains resistant to the
      membrane active antibiotic, gramicidin S].
AB  - Strains of Staphylococcus aureus 209P growing in the presence of 20 micrograms/ml
      of gramicidin S were isolated after the successive subculture on a liquid medium
      with increasing concentrations of the antibiotic. The resistance was stable and
      preserved after the subculture on media not containing the antibiotic. The
      development of the resistance to gramicidin S did not lower the cell sensitivity
      to a large number of antibiotics known as inhibitors of the cell wall synthesis,
      protein synthesis and RNA-polymerase reaction. There was observed the development
      of moderate resistance to actinomycin D but not to other antibiotics interacting
      with DNA. The gramicidin resistant strains were also resistant to tyrocidine, a
      membrane active polypeptide. By the amount of the bound gramicidin S the cells of
      the sensitive and resistant strains did not practically differ.

PMID- 7518669
TI  - A new mock circulatory loop and its application to the study of chemical additive
      and aortic pressure effects on hemolysis in the Penn State electric ventricular
      assist device.
AB  - A new mock circulatory loop was developed for hemolysis studies associated with
      the Penn State electric ventricular assist device (EVAD). This flow loop has
      several advantages over previously designed loops. It is small enough to
      accommodate experiments in which only single units of blood are available, it is
      made out of biocompatible materials, it incorporates good geometry, and it
      provides normal physiological pressures and flows to both the aortic outlet and
      the venous inlet of the pumping device. Experiments with reduced aortic pressure
      but normal cardiac output showed that hemolysis in a loop with normal aortic
      blood pressure was significantly higher than that in a loop with lowered aortic
      pressure, thereby illustrating the importance of maintaining loop pressures as
      close as possible to those found in vivo. This data also imply that blood
      traveling through the left ventricle in an artificial heart may be subject to
      higher hemolysis rates than that traversing the right ventricle. Another set of
      experiments to determine the effects of 4 hemolysis or drag-reducing agents
      (Pluronic F-68, Dextran-40, Polyox WSR-301, and Praestol 2273TR) on blood trauma
      due to the EVAD and associated valves was performed. Results indicated that none
      of the additives significantly reduced hemolysis under the conditions found in
      the mock loop. Finally, a compilation of data gathered in these experiments
      showed that the index of hemolysis (IH) is dependent on hematocrit (HCT), which
      suggests that another parameter, IH/HCT, may be more suited to the quantification
      of hemolysis.

PMID- 7518670
TI  - Effect of increasing intravesicular pH on nitrite production and leishmanicidal
      activity of activated macrophages.
AB  - We examined the effect of bafilomycin A1 (BAF), an inhibitor of vacuolar-type
      H(+)-ATPases, on macrophages activation (measured as increased nitrite production
      and leishmanicidal activity) induced by interferon gamma alone or together with
      lipopolysaccharide or tumour necrosis factor alpha. BAF increased intravesicular
      pH and enhanced nitrite release by activated macrophages; however, the NO
      concentration necessary to kill parasites was higher in BAF-exposed than control
      macrophages, suggesting that microbicidal nitrogen derivatives were less active
      at alkaline pH. Antibody to tumour necrosis factor alpha inhibited BAF-induced
      nitrite production in interferon-activated cultures. To determine if enhanced NO
      synthesis was related to vesicular alkalinization, macrophages were incubated
      with the lysosomotropic bases NH4Cl and methylamine. These agents also increased
      intravesicular pH and nitrite production. Nitrite production was correlated with
      enhanced NO synthase activity in cytosolic extracts of the activated cells.

PMID- 7518672
TI  - Retrotransposition of the Drosophila LINE I element can induce deletion in the
      target DNA: a simple model also accounting for the variability of the normally
      observed target site duplications.
AB  - Retrotransposition of the Drosophila melanogaster LINE I element normally
      generates target site duplications of variable length, as classically observed
      for most LINE elements. Using an I element "marked" with an indicator gene for in
      vivo detection of transposition that we previously developed, we show that
      deletion in the target DNA can also take place, as a direct consequence of I
      element transposition. We propose a simple model accounting for the generation of
      both target site duplications of variable length and target DNA deletions, which
      relies upon template switching of the LINE-encoded reverse transcriptase between
      single-strand DNA at the target site and the LINE template.

PMID- 7518671
TI  - Members of the CAAT/enhancer-binding protein, hepatocyte nuclear factor-1 and
      nuclear factor-1 families can differentially modulate the activities of the rat
      alpha-fetoprotein promoter and enhancer.
AB  - The promoter of the rat alpha-fetoprotein (AFP) gene, which makes the expression
      of the developmentally regulated AFP gene specific to the liver, is a putative
      target for transcription factors of the CAAT/enhancer-binding protein (C/EBP),
      hepatocyte nuclear factor-1 (HNF-1) and nuclear factor-1 (NF-1) families. We have
      evaluated the influence of these factors on the activity of the AFP promoter by
      transfection of HepG2 hepatoma cells with the appropriate expression vector plus
      a CAT plasmid under the control of the AFP promoter. A similar plasmid bearing
      the rat albumin promoter was used as a control. C/EBP alpha, C/EBP beta and D
      binding protein (DBP) acted as trans-activators on the AFP promoter, whereas
      liver inhibitory protein (LIP), a truncated form of C/EBP beta, was a potent
      negative regulator of the promoter. C/EBP alpha also bound to and stimulated the
      activity of the AFP enhancer at -2.5 kb. Interestingly, HNF-1 beta was found to
      be more potent than HNF-1 alpha in activating the AFP promoter. This effect was
      specific, as it did not occur with the rat albumin promoter. HNF-1 beta, which is
      produced earlier than HNF-1 alpha during liver development, would thus have the
      greater influence on the AFP promoter in early development. Both HNF-1s allowed
      expression of the AFP promoter in cells of nonhepatic origin. Overexpression of
      NF-1 induced a specific decrease in the activity of the AFP promoter. This
      strongly suggests that competition between NF-1 and HNF-1 for binding to their
      overlapping binding sites on the AFP promoter is critical for modulating its
      activity. Thus changing combinations of these trans-acting factors may tightly
      modulate the AFP promoter activity in the course of liver development and
      carcinogenesis.

PMID- 7518673
TI  - Spin trapping of nitric oxide by nitronylnitroxides: measurement of the activity
      of no synthase from rat cerebellum.
AB  - Nitric oxide (NO) has been shown to be an important mediator in vasodilation,
      neurotransmission and cellular cytotoxicity. We investigated a new series of
      nitronylnitroxyl radicals (NNR) as spin traps for NO. It was found these radicals
      react with NO with rate constants of about 10(4) M-1c-1 forming stable
      iminonitroxides with dramatic changes in EPR spectra. To overcome fast reduction
      of the radicals (a few seconds in rat cerebella cytosol), NNR with charged
      trimethylammoniophenyl group (Ib) was incorporated into the inner volume of large
      unilamellar phosphatidylcholine liposomes. In this case the reduction of the
      radical Ib in rat cerebella cytosol is slow (ca. 1% per min). The rate of NO
      production by NO synthase from rat cerebellum measured by NNR, Ib, is in a
      reasonable agreement with that obtained by spectrophotometric method.

PMID- 7518674
TI  - Sugar-DNA molecular recognition: specific interaction of alpha-1,4-glucopyranose
      chains with DNA in the minor groove.
AB  - alpha(1,4) glucopyranose chains (dextrins) are shown to interact with DNA via
      hydrophobic interactions from the minor groove side, while alpha(1,6) dextrans do
      not bind DNA. The observed specific alpha(1,4) linked sugar-DNA interactions may
      have importance in recognition of DNA by ene-diyne class of antibiotics via their
      saccharide units which have mostly alpha(1,4) linkages.

PMID- 7518676
TI  - Regulation of glutathione S-transferase gene expression and activity by dietary
      selenium.
AB  - To determine selenium's effects on glutathione S-transferase gene expression and
      enzyme activity, weanling rats were fed a selenium-deficient diet, or the same
      diet supplemented with 0.1 (control) or 2.0 mg selenium/kg diet as sodium
      selenite, for 91 days. Consumption of either the selenium-deficient or high
      selenium diet increased activity of glutathione S-transferase, measured with 1
      chloro-2,4-dinitrobenzene as substrate, compared to the control diet.
      Transcription of genes for glutathione S-transferase subunits was unaffected by
      selenium intake. Steady state levels of mRNA for glutathione S-transferase
      subunits were affected variably by changes in selenium intake, depending upon the
      tissue and subunit examined. These results suggest that the biological effects of
      selenium may be due in part to its regulation of gene expression for glutathione
      S-transferase family enzymes.

PMID- 7518677
TI  - Induction of photoresponse by the hydrolysis of polyphosphoinositides in the
      Hermissenda type B photoreceptor.
AB  - Direct evidence that the photoresponse of the Hermissenda type B photoreceptor
      cell is triggered directly by the hydrolysis of phosphatidylinositol 4,5
      bisphosphate (PIP2) was obtained. Neomycin and spermine, which inhibit PIP2
      breakdown, suppressed light response, while injection of inositol 1,4,5
      trisphosphate (IP3), guanosine 5'-(3-O-thio)triphosphate (GTP gamma S), guanosine
      5'-(2-O-thio)diphosphate (GDP beta S), cAMP, cGMP did not alter the light-induced
      Na+ influx underlying the photoresponse. Suppression of the photoresponse was
      also observed with decrease of total amount of membraneous PIP2 induced by
      injection of the phosphoinositides (PI) turnover inhibitors,
      isobutylmethylxanthine (IBMX), LiCl and R 59022.

PMID- 7518678
TI  - Interaction of tacrolimus(FK506) and its metabolites with FKBP and calcineurin.
AB  - Tacrolimus(FK506) is a strong immuno-suppressant and shows its activity through
      inhibiting IL-2 mRNA transcription by forming pentameric complex with
      intracellular receptor(FK506 binding protein 12 kDa or FKBP12), Ca2+, calmodulin,
      and calcineurin. Here, we report the binding activity to FKBP12, the pentameric
      complex formation and Con-A response inhibiting activities of 7 metabolites. C15
      demethylated metabolite(M-3) needed higher quantity to compete in Con-A assay and
      in pentamer formation assay, although it binds more strongly to FKBP12. The
      result suggests that the ability to form a pentameric complex is not a two step
      reaction with the first binding to FKBP12, but a single step reaction by
      components for the pentamer formation.

PMID- 7518679
TI  - A new variant of muscle phosphofructokinase deficiency in a Japanese case with
      abnormal RNA splicing.
AB  - A genetic defect was investigated in a newly diagnosed Japanese case with muscle
      type phosphofructokinase (PFK-M) deficiency. Polymerase chain reaction (PCR)
      amplification of patient cDNA revealed an in-frame truncation of 165 bases. This
      was compatible to the complete deletion of exon 19. The rest of the sequence was
      identical to that of the normal PFK-M cDNA. Sequencing of PCR amplified genomic
      DNA of the patient revealed a point mutation from G to A at the 5' donor site of
      intron 19. This mutation resulted in the skipping of exon 19 in the patient mRNA.
      Homozygosity of this patient was confirmed by allele specific amplification of
      the genomic DNA. Donor mutations in intron 15 and intron 5 associated with
      different splicing errors were previously reported to cause this disease. Thus,
      the human PFK-M gene mutations are heterogeneous, however, the donor mutations
      and splicing errors would represent one of the frequent causes of this disease.

PMID- 7518675
TI  - Transcription of the MRP RNA gene in frog stage I oocytes requires a novel cis
      element.
AB  - The RNA component of the mitochondrial RNA processing (MRP) enzyme is related to
      both replication of mitochondrial DNA and processing of 5.8S rRNA, which are
      accelerated in the frog earliest stage (stage I) of frog oocytes. Microinjection
      of the deleted genes into the stage I oocytes showed positive cis-elements in the
      upstream region of the gene. The specific binding of protein(s) to this region
      was detected in cell extracts from stage I oocytes and liver but not in extracts
      of stage II-IV oocytes and the concentration of this protein was 40 times higher
      in the extract of stage I oocytes than that in liver.

PMID- 7518680
TI  - Decreased myotonin-protein kinase in the skeletal and cardiac muscles in myotonic
      dystrophy.
AB  - To investigate the role of myotonin-protein kinase (MT-PK) in the pathophysiology
      of myotonic dystrophy (DM), we developed specific antibodies against synthetic MT
      PK peptides. The antibody identified a 53kDa protein in skeletal muscle and
      recognized decreases in the amount of the protein in both adult and congenital DM
      patients, compared with amounts in controls and in patients with other muscle
      diseases. In cardiac muscle, this antibody identified a 62kDa protein, and in
      brain, both the 53 and 62kDa proteins were detected. These results suggest the
      presence of tissue-specific isoforms of MT-PK.

PMID- 7518681
TI  - Tyrosine phosphorylation of JAK-TYK kinases in malignant plasma cell lines growth
      stimulated by interleukins 6 and 11.
AB  - The pleiotropic cytokine interleukin (IL-6) is a major growth factor for murine
      plasmacytomas/hybridomas and human myeloma cells. Here we report that IL-6
      stimulated different patterns of tyrosine phosphorylation of JAK-TYK kinases in
      IL-6-responsive murine (B9E and T10D) and human (ANBL-6 and OCI-My4) plasma cell
      tumor lines. Interestingly, the Stat91 transcription factor essential for
      interferon signaling mediated by JAK-TYK kinases was significantly tyrosine
      phosphorylated in response to IL-6 in ANBL-6 cells but not in the other cell
      lines. We further show that IL-11, a cytokine that signals via the gp130 subunit
      of the IL-6 receptor, induced similar profiles of JAK-TYK tyrosine
      phosphorylation as IL-6 in B9E and T10D cells. These results suggest that
      functionally redundant JAK-TYK kinase cascades triggered through gp130 are
      involved in the growth regulation of plasma cell neoplasms.

PMID- 7518683
TI  - Immune response to different sequences of the EBNA I molecule in Epstein-Barr
      virus-related disorders and in autoimmune diseases.
AB  - Epstein-Barr virus (EBV) infection is associated with production of
      autoantibodies. The N-terminal 35-58 sequence of EBNA I, one of the nuclear
      antigens encoded by EBV, is highly homologous to the C-terminal 95-119 region of
      the ribonucleoprotein SmD. Autoantibodies specific for SmD are present only in
      systemic lupus (SLE) sera and are therefore considered a serological marker of
      SLE. We measured antibodies to the EBNA I 35-58 sequence in EBV-related diseases
      and in autoimmune disorders. Antibodies to the EBNA I 35-58 peptide were present
      in 30% of normal sera, 12% Burkitt lymphoma, 22% infectious mononucleosis, 25%
      rheumatoid arthritis, 38% SLE and 33% Sjogren's syndrome. Antibodies to the SmD
      95-119 peptide were detectable in 32% of SLE sera, 17% infectious mononucleosis
      and 12% Burkitt lymphoma. The specificity of anti-EBNA I 35-58 antibodies
      affinity-purified from nine sera was analysed by means of an inhibition assay.
      Only anti-EBNA I 35-58 antibodies affinity-purified from SLE sera have a similar
      affinity for the viral peptide and the SmD C-terminal one; they also bind the
      recombinant SmD in western blot. The results indicate that antibodies to EBNA I
      35-58 are produced in normals, in EBV-related diseases and in autoimmune
      disorder, but only SLE sera contain anti-viral antibodies cross-reactive with an
      autoantigen.

PMID- 7518682
TI  - Characterization of the human alpha 2-macroglobulin gene promoter: identification
      of a novel, triple TRE/RARE/ERE response element.
AB  - Human alpha 2-macroglobulin is synthesized in the liver and in some extra-hepatic
      tissues but the physiological role of the protein remains unexplained. We
      initiated studies to characterize the promoter of the gene. In transient
      transfections 240 bp of the proximal promoter were necessary and sufficient for
      CAT-expression in HepG2 cells and lung fibroblasts. This promoter was silent in
      skin fibroblasts. In DNAase I footprint analyses, five regions bound nuclear
      factors from expressing and non-expressing cells. FPII (-144 to -104) was most
      prominent with extracts from HepG2 cells and lung fibroblasts. In mobility
      shifts, FPII bound nuclear factors present in the order: HepG2 > lung >> skin
      fibroblasts. This region contains a canonical TRE/RARE/ERE half-site (TGACCT)
      flanked by 2 related hexamers in the combinations PR4 (palindromic repeat,
      spacing 4) and ER1 (everted repeat, spacing 1). The interplay of (orphan) members
      of the steroid receptor family could explain the tissue- and species-specific
      regulation of the alpha 2M gene.

PMID- 7518684
TI  - Identification of antigenic regions of the human 52kD Ro/SS-A protein recognized
      by patient sera.
AB  - Patients with several different connective tissue diseases including Sjogren's
      syndrome and systemic lupus erythematosus produce autoantibodies reacting with a
      52kD protein component of the Ro/SS-A antigen. Antibody recognition of
      recombinant Ro 52kD proteins encoded by both full-length and deletion clones was
      analysed by immunoblotting with patient sera. An antigenic region recognized by
      all anti-Ro 52kD positive sera was found in the middle part of the protein. By
      further mapping of residues 136-292 with overlapping clones, at lest two
      independent epitopes within the domain were detected. This part of the protein
      contains a leucine zipper motif and shows structural similarities with a
      predicted coiled-coil region involved in protein dimer formation. In addition,
      one fifth of the sera reacted weakly with another antigenic region located in the
      amino-terminal part of the protein containing two putative zinc fingers. These
      results demonstrate the presence of an immunodominant region but also
      heterogeneity in the human autoimmune response to the 52kD protein moiety of the
      Ro/SS-A antigen.

PMID- 7518686
TI  - Tissue plasminogen activator in the surgical management of subretinal
      haemorrhage.
AB  - We report three cases of the use of tissue plasminogen activator (TPA) to aid the
      surgical removal of subretinal haemorrhage. All patients had choroidal
      neovascular membranes secondary to age-related macular degeneration. The
      technique involved infusing a sterile solution of TPA through a small retinotomy
      and irrigating out the dissolved clot. The visual acuity improved in the first
      patient from a preoperative 6/36 to 6/18 five weeks after surgery, but
      subsequently deteriorated to 6/60 after six months from a new choroidal
      neovascular membrane (CNVM), remaining 6/60 at nine months after surgery. The
      second patient's visual acuity improved from count fingers to 6/24 three weeks
      after surgery, but subsequently deteriorated to 6/60 after four months from a new
      CNVM, remaining 6/60 at nine months after surgery. The third patient's visual
      acuity improved from count fingers to 6/36 and remains stable at 6/36, eight
      months after surgery. Although long-term prognosis remains guarded, these early
      results suggest that TPA may have a role in the management of subretinal
      haemorrhage.

PMID- 7518685
TI  - [Validity of the Gram and Lendrum stains in conjunctival smears for the
      identification of Chlamydia trachomatis].
AB  - With the objective of finding reliable, valid, and economic diagnostic tests to
      identify Chlamydia trachomatis in conjunctival smears, the sensitivity,
      specificity, and positive and negative predictive values of Lendrum and Giemsa
      stains were evaluated using direct immunofluorescence as the gold standard. In
      addition, inter- and intraobserver reproducibility were estimated through the use
      of two independent observers, who were blinded to the results during their
      readings. The prevalence of ocular chlamydiosis in the study area was around 50%.
      In all, 103 persons (206 eyes) were studied. Three smears from each eye were
      taken for each subject. The kappa statistic was used to estimate the
      reproducibility of the stains. Interobserver reproducibility was null, and
      intraobserver reproducibility ranged between 0.35 and 0.79. The sensitivity of
      the Giemsa stain was a bit higher than that of the Lendrum stain (28% and 22%,
      respectively), and the specificity was similar (82% and 85%, respectively). Based
      on these results, the ability of both stains to detect positive cases was judged
      to be low, as was their reliability. The Lendrum and Giemsa stains are not
      adequate tests for the diagnosis of ocular chlamydiosis. For this purpose the use
      of direct immunofluorescence is recommended.

PMID- 7518687
TI  - Endothelium dependent and independent responses in coronary artery disease
      measured at angioplasty.
AB  - OBJECTIVE--To investigate the effects of substance P and papaverine, two drugs
      that increase coronary blood flow by different mechanisms, on vasomotion in
      stenotic coronary arteries at percutaneous transluminal coronary angioplasty
      (PTCA). DESIGN--Coronary blood flow responses to substance P and papaverine were
      measured in stenotic coronary arteries at the time of PTCA with quantitative
      angiography and a Doppler flow probe. SETTING--A cardiothoracic referral centre.
      PATIENTS--15 patients undergoing elective PTCA of a discrete epicardial coronary
      artery stenosis. INTERVENTIONS--Pharmacological coronary flow reserve was
      determined with papaverine 5-10 minutes before and after successful PTCA.
      Endothelium dependent responses to 2 minute infusions of substance P (10-15
      pmol.min-1) were assessed immediately before PTCA. MAIN OUTCOME MEASURES-
      Coronary blood flow responses and changes in epicardial coronary artery area at
      stenotic, proximal, and distal sites with papaverine and substance P. RESULTS-
      Stenotic sites dilated with papaverine before PTCA (17.7%(6.9%) (mean (SEM)) area
      increase, p < 0.05 v baseline). Substance P dilated stenotic sites (16.8%(5.7%)
      area increase, p < 0.05) and proximal (14.3%(5.4%), p < 0.05) and distal sites
      (41.7%(9.3%), p < 0.005). Coronary flow reserve increased but did not reach
      normal values after PTCA (2.3(0.4) before PTCA v 3.0(0.4) after PTCA, p < 0.05)
      and was associated with an increase in peak flow with papaverine. Angioplasty did
      not alter baseline flow. After PTCA papaverine caused significant
      vasoconstriction at the stenotic site (-13.6%(4.3%) area decrease, p < 0.05).
      There was a negative correlation (r = -0.68, p < 0.05) between the dilator
      response with papaverine before PTCA and the constrictor response after PTCA.
      CONCLUSIONS--Substance P causes endothelium dependent dilatation in atheromatous
      coronary arteries, even at sites of overt atheroma. The cause of the paradoxical
      constrictor response to papaverine after PTCA is uncertain, but unopposed flow
      mediated vasoconstriction (the myogenic response) after balloon induced
      endothelial denudation may be one of several contributory factors.

PMID- 7518690
TI  - Dextran permeation through poly(N-isopropylacrylamide) hydrogels.
AB  - The permeation of macromolecules such as fluoroescein-labeled dextran fractions
      through thermally reversible hydrogels has been investigated. A permeation model
      has been formulated, which takes into account hydrogel porosity and tortuosity as
      well as the combined effect of a geometric restraint for a relatively large
      solute molecule at a pore entrance and the friction between solute molecules
      moving through the pores and pore walls. Based on this model, we have estimated
      the tortuosity and average pore size of a swollen hydrogel, poly(N
      isopropylacrylamide) [poly(NIPAAm)] and a swollen heterogel, poly(N
      isopropylacrylamide-co-vinyl-terminated dimethylsiloxane) [poly(NIPAAm-co
      VTPDMS)]. The permeation data for dextran molecules up to the size of 43.5 A in
      radius show good agreement with the values predicted from the model.

PMID- 7518688
TI  - Population data and forensic efficiency values for the STR systems HumVWA, HumMBP
      and HumFABP.
AB  - Population studies were carried out on Caucasians from north-west Germany using
      the short tandem repeat (STR) systems HumVWA (locus: 12p12-12pter), HumMBP
      (locus: 18q23-pter) and HumFABP (locus: 4q28-q31). After electrophoresis 9
      alleles could be identified for HumVWA in a sample size of 321 unrelated
      individuals and 4 alleles were found for HumFABP in 106 individuals. For HumMBP-A
      10 alleles and for HumMBP-B 7 alleles and 1 intermediate allele were determined
      in a sample size of 143 individuals. No deviations from Hardy-Weinberg
      equilibrium could be observed. In a small family study (HumVWA-n = 129; HumMBP-n
      = 59; HumFABP-n = 48) no new mutations could be found for HumMBP-A and HumFABP
      whereas 2 mutations were found in HumMBP-B and one mutation in HumVWA. Positive
      results could be obtained from 1 ng-20 pg (HumVWA, HumFABP) and 1 ng-100 pg
      (HumMBP) template DNA.

PMID- 7518689
TI  - Distribution and coverage of A- and B-type horizontal cells stained with
      Neurobiotin in the rabbit retina.
AB  - Both A- and B-type horizontal cells in the rabbit retina were labeled by brief in
      vitro incubations of the isolated retina in the blue fluorescent dye 4,6-diamino
      2-phenylindole. Intracellular injection of Lucifer Yellow into the somata
      revealed the morphology of the individual cells. Dye-coupling with Lucifer Yellow
      was seen only between A-type horizontal cells. By contrast, injection of the
      tracer Neurobiotin showed dye-coupling between both A- and B-type horizontal
      cells. There also appeared to be coupling between the axon terminals of B-type
      horizontal cells. The extensive dye-coupling seen following injection of
      Neurobiotin into a single horizontal cell soma can be used to obtain population
      counts of each cell type. Staining of large numbers of each cell type across the
      retina showed that each type increased in number and declined in dendritic
      diameter as the visual streak was approached, such that relatively constant
      coverage across the retina was maintained. In the visual streak, A-type
      horizontal cells numbered 555 cells/mm2 and averaged 120 microns in diameter,
      compared to 1375 cells/mm2 and 100 microns for B-type horizontal cells. In the
      periphery, the A- and B-types numbered 250 cells/mm2 and 400 cells/mm2,
      respectively. The average diameters of the dendritic trees at these locations
      were 225 microns for the A-type and 175 microns for the B-type. Coverage across
      the retina averaged almost six for A-type horizontal cells and 8-10 for the B
      type. A-type horizontal cells in the visual streak whose elliptical dendritic
      fields were shown by Bloomfield (1992) to correlate physiologically with
      orientation bias were shown to be dye-coupled to cells with symmetrical dendritic
      fields.

PMID- 7518691
TI  - Selection of high-affinity RNA ligands to reverse transcriptase: inhibition of
      cDNA synthesis and RNase H activity.
AB  - Specific, high-affinity RNA ligands to avian myeloblastosis virus and Moloney
      murine leukemia virus reverse transcriptases were isolated from a combinatorial
      RNA library using the SELEX (systematic evolution of ligands by exponential
      enrichment) procedure. The selected RNA ligands bound their respective reverse
      transcriptases with approximately nanomolar dissociation constants. The ligands
      did not exhibit primary sequence conservation from selections against different
      target enzymes. Moreover, the selected ligands competed with the binding of
      template/primer complex and inhibited both the RNA-dependent DNA polymerase and
      the RNase H activities of the cognate reverse transcriptase. SELEX can yield both
      high-affinity and high-specificity oligonucleotide antagonists against specific
      members of a protein family.

PMID- 7518694
TI  - The influence of acylation on the lipid structure modulating properties of the
      transmembrane polypeptide gramicidin.
AB  - In order to get insight into the effect of acylation of a transmembrane
      polypeptide on the interaction of the polypeptide with the membrane lipids we
      used 31P-NMR to investigate the influence of acylated gramicidins on the
      polymorphic phase behavior of hydrated dispersions of 1
      palmitoyllysophosphatidylcholine (lyso-PC), 1,2-dioleoylphosphatidylcholine
      (DOPC) and 1,2-dielaidoylphosphatidylethanolamine (DEPE). Palmitoylgramicidin
      induces a micelle to extended bilayer organization in lyso-PC with a slightly
      lower efficiency than the parent gramicidin molecule. In DOPC and DEPE
      acylgramicidins induce the formation of HII phase at the expense of a bilayer
      organization with a similar high efficiency as gramicidin. The ability of
      acylgramicidin to induce lipid mixing between vesicles prepared of DOPC was
      decreased relative to gramicidin. The results are discussed in the light of the
      proposed models for gramicidin-induced HII phase formation and emphasize that
      gramicidin itself has a very strong lipid structure modulating activity.

PMID- 7518692
TI  - Evidence of xenon transport through the gramicidin channel: a 129Xe-NMR study.
AB  - Evidence is presented for Xe transport through the gramicidin A channel. This
      evidence for Xe transport through gramicidin A channels has been obtained using
      129Xe-NMR spectroscopy. Three experiments were utilized. The first experiment
      involved monitoring the change in the chemical shift of 129Xe in the presence of
      increasing gramicidin A concentration, the second observed the effect on the
      129Xe chemical shift with gramicidin A channels photochemically altered by UV
      light and the third determined the effect of gramicidin A channels blocked by
      Ba2+ on the 129Xe chemical shift. The results of these three experiments indicate
      that Xe transports through the gramicidin A channel.

PMID- 7518693
TI  - Trapping of dextran-coated colloids in liposomes by transient binding to
      aminophospholipid: preparation of ferrosomes.
AB  - A procedure is described that allows to increase the efficiency of the loading of
      liposomes with dextran-stabilized iron oxides (MION). The method produces a
      preparation of liposomes (REVs) with high iron oxide content as a result of
      transient binding of oxidized dextran with amino groups of aminophospholipids.
      Phosphatidylethanolamine (PE)-containing lipid mixtures (PC/DOPE/CH or
      SM/DOPE/CH, 9:2:9 molar ratio) in organic phase were combined with oxidized MION
      at pH 8. Liposomes then were obtained by reversed-phase evaporation. Liposomes,
      263 +/- 89 nm in diameter, contained up to 11.8 mol Fe/mol phospholipid
      (encapsulation yield 49%). 10.2% of liposome-associated iron was dissociated from
      liposomes upon changing the pH to 4.5. When lipid compositions of extracts
      prepared from liposomes incubated at pH 4.5 and pH 8.0 were compared, an increase
      of relative PE-content in extracts of liposomes incubated at lowered pH was
      detected. This indicates a dissociation of imine bonds between aldehydes on the
      MION surface and PE. The accessibility of liposomal PE for acylation was
      demonstrated by modification with an activated ester of methoxy poly(ethylene
      glycol) succinate. Control liposomes, containing no aminophospholipid, or PE
      containing liposomes obtained in the presence of non-oxidized MION, were 3.5-5
      fold less effective for MION encapsulation and showed extensive aggregation.

PMID- 7518695
TI  - Gene regulation by the 5'-untranslated region of the platelet-derived growth
      factor A-chain.
AB  - Platelet-derived growth factor (PDGF) A-chain gene contains a long 5'
      untranslated region (5'-UTR) of 850 bp. We evaluated the role of the 5'-UTR by
      chloramphenicol acetyltransferase (CAT) assay. CAT activity appeared when the
      fragment +99 bp downstream from the initiation site (+1) was present but
      disappeared in the fragment to +184 bp. It appeared again at +338 bp but
      disappeared again to +609 bp. The fragment from +99 to +184 inhibited CAT
      activity by a post-transcriptional mechanism, as RNA of CAT was observed but CAT
      activity was not.

PMID- 7518696
TI  - Can childhood disability be ascertained simply in surveys?

PMID- 7518697
TI  - Validity of the ten questions screened for childhood disability: results from
      population-based studies in Bangladesh, Jamaica, and Pakistan.
AB  - An international study to validate the Ten Questions screen for serious childhood
      disability was undertaken in communities in Bangladesh, Jamaica, and Pakistan,
      where community workers screened more than 22,000 children ages 2-9 years. All
      children who screened positive, as well as random samples of those who screened
      negative, were referred for clinical evaluations. Applying comparable diagnostic
      criteria, the sensitivity of the screen for serious cognitive, motor, and seizure
      disabilities is acceptable (80-100%) in all three populations, whereas the
      positive predictive values range from 3 to 15%. These results confirm the
      usefulness of the Ten Questions as a low-cost and rapid screen for these
      disabilities, although not for vision and hearing disabilities, in populations
      where few affected children have previously been identified and treated. They
      also show that the value of the Ten Questions for identifying disability in
      underserved populations is limited to that of a screen; more thorough evaluations
      of children screened positive are necessary to distinguish true- from false
      positive results and to identify the nature of the disability if present.

PMID- 7518698
TI  - Development of enzyme immunoassays specific for keratan sulphate- and core
      protein-epitopes of the large aggregating proteoglycan from human articular
      cartilage.
AB  - In the course of chronic inflammatory and degenerative joint diseases
      proteoglycans are degraded by the action of proteases and oxygen radicals.
      Therefore, proteoglycan fragments, released from cartilage into the peripheral
      blood, might be useful markers of cartilage degradation. Sensitive enzyme
      immunoassays are useful for the detection of these proteoglycan fragments in
      serum. We therefore developed specific monoclonal antibodies against the large
      aggregating proteoglycan (aggrecan), which has been isolated and purified from
      human articular cartilage. Two monoclonal antibodies which recognize a novel
      cartilage-specific epitope on the keratan sulphate chain of aggrecan (mAb
      4B3/D10) and an epitope of the core-protein of aggrecan (4G4/A10) were selected
      for the development of competitive enzyme-immunoassays. These assays allow the
      sensitive and specific detection of cartilage-derived proteoglycan fragments, not
      only in synovial fluid but also in serum. They can now be used for the study of
      inflammatory and degenerative joint diseases.

PMID- 7518700
TI  - Carotid body chemoreception: mechanisms and dynamic protection against apnea.
AB  - A critical role of peripheral chemoreceptors in terminating apnea and in
      initiating normal breathing has been emphasized. Since these are the only organs
      which signal hypoxia, failure of its adequate development can contribute to the
      disease of respiratory failure in neonatal life. The failure may reside in any of
      the steps from initiation of O2 chemoreception involving respiratory and non
      respiratory pigments, ion balance including H+ and Ca2+, neurotransmitter
      mechanisms and transduction.

PMID- 7518699
TI  - Synthesis of tissue factor pathway inhibitor in human synovial cells and
      chondrocytes makes joints the predilected site of bleeding in haemophiliacs.
AB  - The synthesis of tissue factor pathway inhibitor (TFPI) was investigated in
      cloned human synovial cells and human chondrocytes. TFPI-specific DNA
      transcription products of these cells were isolated, and a full-length cDNA of
      about 1000 base pairs was amplified by reverse transcription and polymerase chain
      reaction. The amplified DNA was cloned into the vector pUC 18. The TFPI coding
      sequence was confirmed by double stranded sequencing and was identical with that
      previously published for human TFPI coding nucleotide sequence from human
      placental cDNA (1). The inhibitory activity of TFPI in the cell medium of
      cultivated human chondrocytes and cloned human synovial cells was determined by a
      specific chromogenic substrate assay of factor Xa activity. The inhibitory
      activity of TFPI in the medium of human chondrocytes and cloned human synovial
      cells was 630-720 mU/10(8) cells and 1080-1665 mU/10(8) cells, respectively. In
      addition, TFPI activity in cell culture media of human chondrocytes and cloned
      human synovial cell was suppressed by a polyclonal goat anti-TFPI antibody
      directed against the inhibitory domain I and domain II. In the chromogenic
      substrate assay, the anti-TFPI antibody completely suppressed the inhibitory
      activity of TFPI in the samples.

PMID- 7518701
TI  - Combination therapy for infection due to human immunodeficiency virus type 1.
AB  - The preliminary results of the Concorde trial demonstrated the transient clinical
      benefit of monotherapy with zidovudine (AZT) in asymptomatic persons infected
      with human immunodeficiency virus type 1 (HIV-1). This result, which has been
      widely disseminated and discussed, was predictable given the previous
      demonstration of the development of resistance to AZT in isolates from
      individuals receiving prolonged treatment with the drug and given the finding
      that didanosine (ddI) is more efficacious than continued therapy with AZT in
      individuals who have received > or = 6 months of AZT monotherapy. On the basis of
      these findings, interest in combinations of antiretroviral agents has continued
      to grow. Many in vitro studies of nucleoside and nonnucleoside inhibitors of
      reverse transcriptase combined with interferon-alpha or inhibitors of protease
      have been published. In addition, numerous clinical trials of various
      combinations have been completed or are under way. Dr. Martin Hirsch and his
      colleagues at the Massachusetts General Hospital have been among the leaders of
      this effort. He and Dr. Angela Caliendo review, in this AIDS Commentary, the
      current state of our knowledge regarding the potential utility of combination
      therapy for infection with HIV-1.

PMID- 7518702
TI  - Reconstitution of expressed KCa channels from Xenopus oocytes to lipid bilayers.
AB  - Reconstitution of large conductance calcium-activated potassium (KCa) channels
      from native cell membranes into planar lipid bilayers provides a powerful method
      to study single channel properties, including ion conduction, pharmacology, and
      gating. Recently, KCa channels derived from the Drosophila Slowpoke (Slo) gene
      have been cloned and heterologously expressed in Xenopus oocytes. In this report,
      we describe the reconstitution of cloned and expressed Slo KCa channels from
      Xenopus oocyte membranes into lipid bilayers. The reconstituted channels
      demonstrate functional properties characteristic of native KCa channels. They
      possess a mean unitary conductance of approximately 260 pS in symmetrical
      potassium (250 mM), and they are voltage- and calcium-sensitive. At 50 microM
      Ca2+, their half-activation potential was near -20 mV; and their affinity for
      calcium is in the micromolar range. Reconstituted Slo KCa channels were
      insensitive to external charybdotoxin (40-500 nM) and sensitive to micromolar
      concentrations of external tetraethylammonium (KD = 158 microM, at 0 mV) and
      internal Ba2+ (KD = 76 microM, at 40 mV). In addition, they were blocked by
      internally applied "ball" inactivating peptide (KD = 480 microM, at 40 mV). These
      results demonstrate that cloned KCa channels expressed in Xenopus oocytes can be
      readily incorporated into lipid bilayers where detailed mechanistic studies can
      be performed under controlled internal and external experimental conditions.

PMID- 7518704
TI  - Myelin basic protein interaction with zinc and phosphate: fluorescence studies on
      the water-soluble form of the protein.
AB  - The interaction of myelin basic protein (MBP) with zinc and phosphate ions has
      been studied by using the emission properties of the single tryptophan residue of
      the protein (Trp-115). The studies have been carried out by means of both static
      and time-resolved fluorescence techniques. The addition of either zinc to MBP in
      the presence of phosphate or phosphate to MBP in the presence of zinc resulted in
      an increase of fluorescence intensity and a blue shift of the emission maximum
      wavelength. Furthermore, a concomitant increase in the scattering was also
      detected. Anisotropy decay experiments demonstrated that these effects are due to
      the formation of MBP molecules into large aggregates. A possible physiological
      role for such interaction is discussed.

PMID- 7518703
TI  - Brownian dynamics study of a multiply-occupied cation channel: application to
      understanding permeation in potassium channels.
AB  - The behavior of a multiply-occupied cation-selective channel has been computed by
      Brownian dynamics. The length, cross-section, ion-ion repulsion force, and ionic
      mobility within the channel are all estimated from data and physical reasoning.
      The only free parameter is a partition energy at the mouth of the channel,
      defining the free energy of an ion in the channel compared to the bath. It is
      presumed that this partition energy is associated with the energetics of
      exchanging a bulk hydration environment for a channel hydration environment.
      Varying the partition energy alone, keeping all other parameters fixed, gives
      approximately the full range of magnitudes of single channel conductances seen
      experimentally for K channels. Setting the partition energy at -11 kT makes the
      computed channel look similar to a squid axon K channel with respect to magnitude
      of conductance, shape of the I-V curve, non-unity of Ussing flux ratio exponents,
      decrease of current and increase of conductance with extracellular ion
      accumulation, and saturation at high ion concentration in the bathing solution.
      The model includes no preferred binding sites (local free energy minima) for ions
      in the channel. Therefore it follows that none of the above-mentioned properties
      of K channels are strong evidence for the existence of such sites. The model does
      not show supersaturation of current at very high bathing concentrations nor any
      pronounced voltage-dependence of the Ussing flux ratio exponent, suggesting that
      these features would require additional details not included in the model
      presented herein.

PMID- 7518705
TI  - 250-GHz electron spin resonance studies of polarity gradients along the aliphatic
      chains in phospholipid membranes.
AB  - Rigid-limit 250-GHz electron spin resonance (FIR-ESR) spectra have been studied
      for a series of phosphatidylcholine spin labels (n-PC, where n = 5, 7, 10, 12,
      16) in pure lipid dispersions of dipalmitoylphosphatidylcholine (DPPC) and 1
      palmitoyl-2-oleoylphosphatidylcholine (POPC), as well as dispersions of DPPC
      containing the peptide gramicidin A (GA) in a 1:1 molar ratio. The enhanced g
      tensor resolution of 250-GHz ESR for these spin labels permitted a careful study
      of the nitroxide g-tensor as a function of spin probe location and membrane
      composition. In particular, as the spin label is displaced from the polar head
      group, Azz decreases and gxx increases as they assume values typical of a
      nonpolar environment, appropriate for the hydrophobic alkyl chains in the case of
      pure lipid dispersions. The field shifts of spectral features due to changes in
      gxx are an order of magnitude larger than those from changes in Azz. The magnetic
      tensor parameters measured in the presence of GA were characteristic of a polar
      environment and showed only a very weak dependence of Azz and gxx on label
      position. These results demonstrate the significant influence of GA on the local
      polarity along the lipid molecule, and may reflect increased penetration of water
      into the alkyl chain region of the lipid in the presence of GA. The spectra from
      the pure lipid dispersions also exhibit a broad background signal that is most
      significant for 7-, 10-, and 12-PC, and is more pronounced in DPPC than in POPC.
      It is attributed to spin probe aggregation yielding spin exchange narrowing. The
      addition of GA to DPPC essentially suppressed the broad background signal
      observed in pure DPPC dispersions.

PMID- 7518707
TI  - Evaluation of the sensitivity, specificity, and predictive value of monoclonal
      antibody 3F6 for the detection of Pneumocystis carinii pneumonia in
      bronchoalveolar lavage specimens and induced sputum.
AB  - The sensitivity and specificity of different staining procedures for the
      detection of Pneumocystis carinii organisms were compared. Three conventional
      stains (Papanicolaou, Giemsa and Grocott's) and one immunocytochemical stain
      using 3F6 antibody were used on smears prepared from the same specimen.
      Bronchoalveolar lavage (BAL) and induced sputum (IS) specimens were used for this
      purpose. One hundred and sixty-five episodes from 142 patients were investigated
      by the four different staining techniques. Cysts of P. carinii were detected in
      64 episodes from 63 patients. Immunocytochemical staining with 3F6 was found to
      be slightly more sensitive at detecting the cysts than Grocott's, Giemsa, or
      Papanicolaou stain.

PMID- 7518706
TI  - Ion flow in the bath and flux interactions between channels.
AB  - We present an exact solution to the linearized Nernst-Planck-Poisson equation for
      spherically symmetric current flow. This solution differs from Levitt's solution
      (Levitt, D. G. 1992. Biophys. J., Eq. A5) by its dependence on an additional
      parameter, which is equal to the net ion flux for monovalent ion-selective
      channels. For ion-selective channels, this solution may provide better boundary
      conditions to modelling the flow in the channel pore itself, although only at low
      salt concentrations. We use the solution to estimate the effects of flux
      interaction between closely packed channels.

PMID- 7518708
TI  - Ribosomal RNA-based methods for fingerprinting prokaryotes.

PMID- 7518709
TI  - Expression of CA19-9, DU-PAN-2, and SPan-1 antigens on two types of normal
      salivary mucins.
AB  - Mucins are important in cancer diagnosis and therapy. A better understanding of
      the characteristics of mucins in normal and malignant tissues could make them
      more effective clinical targets. Levels of the sialylated carbohydrate mucin
      antigens CA19-9, DU-PAN-2, SPan-1, and TAG-72 are elevated in sera from patients
      with pancreatic cancer. In this study we examined normal saliva for the presence
      of these antigens. TAG-72 reactivity was not detected in the samples examined.
      SPan-1 expression correlated with the expression of CA19-9 except in Le(a)-
      individuals. In these individuals CA19-9 was absent; SPan-1 was expressed to
      varying degrees. Little, if any, reactivity was detected with four monoclonal
      antibodies directed against the MUC1 mucin peptide. A high-buoyant-density
      fraction (1.35 to 1.55 g/mL) of normal saliva, containing most of the sialic
      acids and O-linked oligosaccharides, was separated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). Western blots showed that CA19-9,
      DU-PAN-2, and SPan-1 antigens were found on two forms of mucins. DU-PAN-2
      reactivity was detected only in the absence of the sulfhydryl reducing agent beta
      mercaptoethanol. The two main forms of antigens differed in molecular size (150
      kDa and greater than 400 kDa) and buoyant density (1.38 and 1.49 g/mL) and have
      been reported to differ in amino-acid composition. In colon or pancreas, the CA19
      9, DU-PAN-2, and SPan-1 carbohydrate structures have been reported to be present
      on the MUC1 mucin peptide. Our present results suggest that in saliva, these
      carbohydrate antigens may be found on mucin peptides other than MUC1.

PMID- 7518710
TI  - Tacrolimus, a new immunosuppressant--a review of the literature.
AB  - OBJECTIVE: To review the clinical pharmacology, pharmacokinetics, adverse
      effects, therapeutic uses, and current status of tacrolimus. DATA SOURCES: Data
      from scientific literature were identified by a MEDLINE search. The data were
      extracted, evaluated, and summarized for presentation. Experiences from studies
      evaluating tacrolimus in the form of articles, abstracts, letters to the editor,
      or proceedings were considered for inclusion. STUDY SELECTION: Open and
      controlled clinical and animal trials were reviewed in evaluating the
      pharmacology, pharmacokinetics, and adverse effects of tacrolimus. DATA
      EXTRACTION: Data from animal and human studies published in the English
      literature were evaluated. DATA SYNTHESIS: Tacrolimus is an 822-kDa macrolide
      antibiotic that has potent immunosuppressive properties. The mechanism of action
      is similar to that of cyclosporine in that it ultimately blocks the production of
      interleukin 2, thereby inhibiting further T-lymphocyte proliferation. Tacrolimus
      is metabolized solely in the liver and the metabolites are primarily excreted in
      the bile. The elimination half-life of tacrolimus is approximately 8.5 h, and is
      prolonged in hepatic dysfunction. Tacrolimus has shown efficacy in the
      prophylaxis of allograft rejection in both animals and human clinical trials, and
      has been used effectively to rescue patients who have exhibited refractory
      rejection failing cyclosporine prophylaxis. Adverse effects requiring tacrolimus
      dosage adjustment include nephrotoxicity, neurotoxicity, alterations in glucose
      metabolism, and infection or susceptibility to malignancy. CONCLUSIONS: To date,
      trials comparing tacrolimus with cyclosporine are not available in the
      literature; however, tacrolimus appears to be useful in rescuing grafts,
      particularly liver grafts that fail cyclosporine-based immunosuppression. Direct
      comparisons with cyclosporine are needed to define the role of tacrolimus as
      primary transplant therapy.

PMID- 7518711
TI  - Glossary of cytokines.

PMID- 7518712
TI  - Cytokine receptors and signal transduction.
AB  - The past few years have seen an explosion in the identification, cloning and
      characterization of cytokines and their receptors. The pleiotropic effects of
      many of the growth factors and the considerable redundancy in the actions of
      growth factors have contributed to a mass of descriptive literature that often
      seems to defy summary. Only recently have common concepts begun to emerge. First,
      cytokines mediate their effects through a large family of receptors that have
      evolved from a common progenitor and retain structural and functional
      similarities. Within the haematopoietic system, the cytokines are not usually
      instructive in differentiation, but rather supportive, and may contribute to some
      differentiation-specific responses. The patterns of expression of cytokine
      receptors are therefore a product of differentiation and provide for changes in
      physiological regulation. The second important concept that is emerging is that
      the cytokines mediate their mitogenic effects through a common signal-transducing
      pathway involving tyrosine phosphorylation. Thus, although the cytokine receptor
      superfamily members do not have intrinsic protein tyrosine kinase activity, by
      coupling to activation of tyrosine phosphorylation they may affect cell growth by
      pathways that are common with the large family of growth factor receptors that
      contain intrinsic protein tyrosine kinase activity. The coupling of cytokine
      binding to tyrosine phosphorylation and mitogenesis requires a relatively small
      membrane-proximal domain of the receptors. This region has limited sequence
      similarity which may be required for the association of individual receptors with
      an appropriate kinase. Activation of kinase activity results from the
      dimerization or oligomerization of receptor homodimers or heterodimers. Again
      this requirement is similar to that seen with the growth factor receptors which
      have intrinsic protein tyrosine kinase activity. The protein tyrosine kinases
      that couple cytokine binding to tyrosine phosphorylation are members of the Jak
      family of kinases. The ubiquitous expression of these kinases provides a common
      cellular background on which the cytokine receptors can function and on which
      unique functionally distinct receptors have evolved. In particular, tyk2 is
      required for the responses initiated by IFN-alpha while Jak2 has been implicated
      in the responses to G-CSF, IL-3, EPO, growth hormone, prolactin and IFN
      gamma.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7518713
TI  - The interferons in haematological malignancies.
AB  - Interferons (IFNs) are a family of biological response modifiers with a broad
      spectrum of action on cellular proliferation as well as immunoregulation. In the
      last decade, these properties have prompted several investigations of the effect
      of IFNs on various haematological malignancies. IFNs-alpha have been used most
      extensively. The response rate is dependent on the type of the disease. The most
      striking effects have been observed in hairy cell leukaemia and chronic myeloid
      leukaemia. In both these malignancies the results are well consolidated and
      indicate that IFNs-alpha have modified the natural history of the disease.
      Results of IFN therapy in low grade lymphoma, cutaneous T-cell lymphoma and
      multiple myeloma suggest a beneficial role of IFNs-alpha in the induction, as
      well as the maintenance, phase. The efficacy of IFNs is now widely confirmed in
      treating patients with essential thrombocythaemia or polycythaemia vera. However,
      the role of IFNs in the management of chronic lymphocytic leukaemia and
      myelofibrosis with myeloid metaplasia is still controversial.

PMID- 7518714
TI  - Cord blood mononuclear cell responsiveness to beta-lactoglobulin: T-cell activity
      in 'atopy-prone' and 'non-atopy-prone' newborns.
AB  - We have studied the T-cell-mediated response to the major allergen of cow's milk,
      in a group of newborns at risk of developing cow's milk allergy, and in a control
      group. Before any atopic status has developed, we observe beta-lactoglobulin
      specific primary proliferation only in the group at risk for food-related
      allergies. In this group, the capability to proliferate is not due to placental
      transmission of 'factors' from allergic mothers. The recognition of the tested
      beta-lactoglobulin peptides does not show major differences between the responder
      and nonresponder populations. In the responder population, the response to p145
      161 appears linked to a primary response to ovalbumin, another frequent food
      allergen. On the basis of our findings, we propose a model in which development
      of allergic diseases is linked to an alteration of T-cell activation through the
      engagement by the antigen; the HLA phenotype determines the allergen(s) involved,
      and other genetic or environmental factors dictate the clinical characteristics
      of the disease.

PMID- 7518715
TI  - Characterization of the 18-kDa apple allergen by two-dimensional immunoblotting
      and microsequencing.
AB  - A low-temperature extract taken from Golden Delicious apples was separated by two
      dimensional polyacrylamide gel electrophoresis. By means of two-dimensional
      immunoblotting with patients' serum containing IgE specific to Bet v I, a rabbit
      polyclonal antiserum raised against Bet v I, and two Bet v I specific monoclonal
      antibodies, epitopes cross-reactive to Bet v I were identified on an apple
      allergen with a molecular mass of 18 kDa and pI 5.5. Furthermore, certain
      antibody reactivities with 4 isoproteins of a molecular mass of 16 kDa and pIs
      ranging from 4.9 to 5.5 were observed, which may indicate the presence of Bet v I
      related epitopes on these proteins. Based on 26 amino acid residues, N-terminal
      sequencing of the 18-kDa apple allergen revealed 62% sequence identity between
      Bet v I from birch pollen and the apple allergen. Our results therefore support
      the view that both proteins express common as well as non-related IgE-reactive
      epitopes.

PMID- 7518717
TI  - Issues of variability, carryover contamination, and detection in 3SR-based
      assays.

PMID- 7518716
TI  - Proliferation and activation of vascular endothelial cells in epiretinal
      membranes from patients with proliferative diabetic retinopathy. An
      immunohistochemistry and clinical study.
AB  - In the present study, we investigated the status of proliferation and activation
      of vascular endothelial cells in epiretinal membranes from patients with
      proliferative diabetic retinopathy (PDR) by means of immunohistochemical
      techniques and compared the findings with the main clinical features of the
      patients. The results showed that of 21 vascularized membranes, 17 (81%)
      contained proliferating endothelial cells (positive for proliferating vascular
      endothelial cell marker EN 7/44) and 19 (90%) were positive for endothelial cell
      activation marker anti-VCAM-1; Furthermore, by using a double-staining technique
      we found that in 15 of the 17 cases (88%) the proliferating vascular endothelial
      cells were activated (expressing VCAM-1). Of the 18 type I diabetics, 15 (83%)
      contained activated proliferating endothelial cells, whereas in the 3 type II
      patients, only 1 membrane contained activated proliferating endothelial cells,
      Preoperatively, 18 patients had severe vitreous hemorrhage, among whom 15 (83%)
      contained proliferating endothelial cells, which were activated in 13 cases, and
      16 patients had tractional retinal detachment, among whom 12 contained
      proliferating endothelial cells, which were activated in 11 cases. In all, 7
      patients (33%) had vitreous rebleeding within 8 months postoperatively, whose
      membranes in 6 cases contained proliferating and activated endothelial cells. In
      contrast, of the 4 patients who were negative for EN 7/44, none had rebleeding,
      and of the 6 patients who were negative for EN 7/44 and anti-VCAM-1, only 1 had
      rebleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518718
TI  - RNA associated with a heterodimeric protein that activates a meiotic homologous
      recombination hot spot: RL/RT/PCR strategy for cloning any unknown RNA or DNA.
AB  - The ade6-M26 mutation in the fission yeast Schizosaccharomyces pombe creates a
      meiotic homologous recombination hot spot. We have achieved 40,000-fold
      purification of a heterodimeric DNA-binding protein, Mts1/Mts2, that activates
      the recombination hot spot. Physical studies suggested the presence of a third
      subunit. It is demonstrated here that RNA molecules of approximately 210
      nucleotides copurified with the heterodimer. To characterize the RNA component,
      it was necessary to develop a new strategy for cloning of the unknown, low
      abundance, partially degraded RNAs that were present in purified Mts1/Mts2
      protein preparations. The strategy uses RNA ligase to add DNA oligonucleotide
      priming sites to the RNA for subsequent reverse transcription and PCR (RNA
      ligase, reverse transcription-PCR, or RL/RT/PCR). This cloning procedure could be
      applied to the cloning of any unknown RNA or DNA molecules. Because the cDNA
      clones obtained from Mts1/Mts2 were largely heterogeneous, it seems likely that
      the RNAs copurified as a result of tight but nonspecific interactions with the
      heterodimeric protein.

PMID- 7518719
TI  - Quantitative analysis of CD34+ stem cells using RT-PCR on whole cells.
AB  - We have employed RT-PCR of whole cells to develop a quantitative method for
      estimating the number of rare cells expressing a unique mRNA in a large, mixed
      population of cells. We have demonstrated that RT-PCR can be done on whole cells
      without the need for extraction of the RNA. This allows for a great saving of
      time and effort, as well as allowing quantitative analysis to be based on the
      total number of cells analyzed in a given aliquot and the presence or absence of
      the specific RT-PCR product. We have employed a limiting dilution series on whole
      cells, with multiple aliquots at each cell concentration to achieve more
      statistical power in the analysis of a rare cell type. We have used a nested
      amplification of the CD34 mRNA to be able to detect a single cell expressing the
      CD34 mRNA in a larger population of non-CD34-expressing cells. We demonstrate
      that by using this technique, cells from blood and bone marrow containing the
      CD34 mRNA can be followed quantitatively during a multistep purification
      involving immunoadsorption followed by fluorescence-activated cell sorting. We
      also demonstrate that many cells that express the CD34 protein on their surface
      no longer contain detectable levels of CD34 mRNA, a phenomenon that appears to be
      developmentally regulated.

PMID- 7518720
TI  - Immunological approach for the identification of isozymes of CAM-stimulated
      phosphatase.
AB  - Monoclonal antibodies are frequently used to identify protein isoforms. The
      present study documents certain artifacts in such applications and suggests
      methods for their testing. Two alpha subunit specific anti-calcineurin
      antibodies, VJ6 and VD3, reacted strongly with a brain isozyme, BPI, but not with
      the phosphatases from liver and spleen. Controlled proteolysis of BPI indicated
      that epitopes of both antibodies are localized to aminoterminal region, thus is
      suggesting that the lack of antibody reactivity could result from proteolytic
      artifacts. The occurrence of proteolysis during sample preparation can be
      monitored by including small quantity of BPI in the tissue extraction buffer.
      Rapid isolation procedure has been used to obtain liver and spleen isozymes
      reacting with VD3 but not VJ6 antibody.

PMID- 7518721
TI  - Tissue distribution of ecto-Mg-ATPase in adult and embryonic chicken.
AB  - We have determined the distribution of chicken ecto-Mg-ATPase in a variety of
      tissues from adult and embryonic chicken. The presence of ecto-Mg-ATPase was
      identified by an antibody raised against a 12 amino acid residue peptide, NH2
      KILSGEEEGVFG, derived from proteolysis and sequencing of the chicken gizzard ecto
      Mg-ATPase. Adult chicken tissues were also assayed for ATPase activity in the
      presence/absence of stimulators/inhibitors of the ecto-ATPase in order to confirm
      the immunologic tissue distribution results. There is controversy in the
      literature as to the size(s) of ecto-Mg-ATPases. We demonstrate here that the
      apparent size of the enzyme(s) recognized by anti-peptide antibodies by Western
      blot analysis depends on the denaturation conditions used prior to
      electrophoresis. Lastly, we deduce that the chicken ecto-ATPase is not identical
      to T-cadherin, as has been recently proposed.

PMID- 7518722
TI  - Use of NIPPV in terminal respiratory insufficiency.

PMID- 7518724
TI  - Age-related changes in nerve growth factor receptor immunoreactive neurons in the
      magnocellular basal forebrain system in rat brain--an immunocytochemical and
      morphometric study.
AB  - Morphometrical changes with aging in nerve growth factor receptor (NGFR)
      immunoreactive neurons in the basal forebrain were studied in juvenile and aged
      rat brains by means of NGFR immunohistochemistry. The nucleus basalis of Meynert
      (NBM) had cell loss and atrophy of NGFR immunoreactive neurons, and the
      horizontal nucleus of diagonal band of Broca (HNDB) showed only atrophy of these
      neurons. The medial septal nucleus and vertical nucleus of diagonal band of Broca
      had no significant change. Neuropil NGFR immunostaining was reduced in its
      intensity in the aged rats. As nerve growth factor is synthesized in the target
      areas and retrogradely transported to the nerve cell body within the basal
      forebrain and NGFR immunoreactive neurons are largely cholinergic ones,
      degeneration of NGFR-positive neurons in the basal forebrain may be related to a
      decreased cholinergic activity. The degeneration of the dendrites of NGFR
      immunoreactive neurons were reported to be extensively found in the basal
      forebrain nuclei, in contrast, degeneration of the cell body of NGFR
      immunoreactive neurons was confined to those in the NBM and HNDB in the present
      study. These findings suggest that atrophic changes in the dendrites precede
      those in the cell bodies of NGFR-immunoreactive neurons.

PMID- 7518725
TI  - Further complexities of the Rh antigen D disclosed by testing category DII cells
      with monoclonal anti-D.
AB  - The reaction pattern of monoclonal anti-D with category DII cells differed from
      those of other category D cells. DII cells express epD1, epD2, epD3, epD5, epD6/7
      and epD8 but lack epD4 and a new epitope epD9. The new epitope, epD9, is proposed
      to explain the failure of some monoclonal anti-D (previously considered to be
      anti-epD3) to react with DII cells.

PMID- 7518723
TI  - Influence of internal calcium stores on calcium-activated membrane currents in
      smooth muscle.
AB  - Agonist-induced activation of second messenger systems that increase inositol
      1,4,5-trisphosphate concentration plays an important role in the mobilisation of
      stored Ca2+ in smooth muscle. Release of Ca2+ which occurs spontaneously or by
      agonist stimulation causes activation of Ca(2+)-sensitive currents. Experiments
      using selective modulators of the Ca2+ uptake and release mechanisms of the
      sarcoplasmic reticulum provide evidence that depletion of the internal Ca2+ store
      triggers an influx of Ca2+ from the extracellular space. Recent data suggest that
      pool depletion causes the opening of non-selective cation channels which are
      possibly similar to those previously designated 'receptor-operated Ca2+
      channels'. Ca2+ entry through these channels not only refills the internal Ca2+
      pool, but also modulates membrane excitability by stimulating Ca(2+)-activated
      currents.

PMID- 7518726
TI  - Clinical utility of insulin-like growth factor binding protein-3 in the
      evaluation and treatment of short children with suspected growth hormone
      deficiency.
AB  - We have shown previously that serum insulin-like growth factor binding protein-3
      (IGFBP-3) levels have good predictive value for complete, but not partial, growth
      hormone deficiency (GHD). In this study, we compare IGFBP-3 levels in short
      children previously divided into groups on the basis of their post-stimulation GH
      levels. Complete GHD (N = 59) included those children with peak post-stimulation
      GH < 5 micrograms/l. The partial GHD group (N = 49) had post-stimulation GH peaks
      of > 5 micrograms/l but < 10 micrograms/l. The normal children with short stature
      (N = 103) had post-stimulation GH peaks > 10 micrograms/l. Partial GHD and normal
      children with short stature also were divided into either low IGF-I or normal IGF
      I subgroups. The clinical sensitivity of IGFBP-3 for complete GHD was 92%,
      whereas its sensitivity for partial GHD was 39%. For partial GHD, among those
      with low IGF-I (N = 19) 68% were also low for IGFBP-3, while 80% of those with
      normal IGF-I (N = 30) were also normal for IGFBP-3. The clinical specificity of
      IGFBP-3 for normal children with short stature was 69%. For these groups, among
      those with low IGF-I (N = 22) 73% also were low for IGFBP-3, while 80% of those
      with normal IGF-I (N = 81) also were normal for IGFBP-3. In addition, we tested
      whether IGFBP-3 can predict the response to GH treatment in prepubertal children
      by comparing pretreatment IGFBP-3 with the height gain achieved by 1 year of GH
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518727
TI  - Effects of repeated subcutaneous administration of recombinant human insulin-like
      growth factor I in adults with growth hormone deficiency.
AB  - Insulin-like growth factor I (IGF-I) circulates bound to specific binding
      proteins (BPs) that modulate its effects at target cells. Hypoglycemia alters the
      serum levels of insulin-dependent IGFBPs and thus modifies the IGF-I action. We
      administered recombinant IGF-I (40 micrograms/kg body wt, from Kabi Pharmacia) in
      a morning dose (08.00 h) for seven consecutive days to six patients (21-47 years)
      with panhypopituitarism. This dose did not lead to hypoglycemia. Repeated blood
      sampling was performed on days 1 and 7, otherwise morning samples were drawn. The
      mean serum total IGF-I was maximal 3-4 h after the injection. A higher peak and
      basal value (p < 0.05) was observed on day 7 when compared to that observed on
      day 1. The concentrations were 237 vs 190 micrograms/l and 43 vs 22 micrograms/l.
      The mean free IGF-I increased concomitantly to 17 and 20 micrograms/l after 2-3 h
      on days 1 and 7. After 4 h, IGF-II was decreased (p < 0.05) from 340 to 291
      micrograms/l on day 1 and from 341 to 252 micrograms/l on day 7. The IGF-I area
      under the curve on days 1 and 7 was correlated to the IGFBP-3 levels. Only the
      patient with the highest IGFBP-3 level obtained IGF-I levels above 100
      micrograms/l for 24 h. In spite of unchanged glucose levels, there was a modest
      suppression of insulin levels (p < 0.05) between 0 and 4 h from 102 to 78 pmol/l
      on day 1 and from 90 to 60 pmol/l on day 7 when the subjects were
      fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518729
TI  - Antenatal maternal serum profiles.
AB  - Since the late 1970s antenatal biochemical screening for pregnancies associated
      with neural tube defects has become a routine part of obstetric practice in the
      UK. More recently, biochemical screening programmes for chromosomal anomalies
      such as trisomy 21 (Down's syndrome) and trisomy 18 (Edward's syndrome) have
      moved on from the research stage and have begun to be implemented.

PMID- 7518728
TI  - Growth hormone (GH) treatment increases serum insulin-like growth factor binding
      protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content
      in young adults with GH deficiency of childhood onset.
AB  - Recent studies have demonstrated that growth hormone (GH)-deficient adults have a
      markedly decreased bone mineral content compared to healthy adults. However,
      there are conflicting results regarding the effects of GH treatment on bone
      mineral content in GH-deficient adults. Therefore, we evaluated the effect of GH
      treatment on a marker of bone formation (bone alkaline phosphatase), hepatic
      excretory function and distal forearm bone mineral content in GH-deficient
      adults. Growth hormone was administered subcutaneously in 21 adults (13 males and
      8 females) with GH deficiency of childhood onset for 4 months in a double-blind,
      placebo-controlled GH trial, while 13 of the patients then received further GH
      for an additional 14 months. Serum insulin-like growth factor I (IGF-I) increased
      significantly from 100 to 279 micrograms/l and IGF binding protein-3 (IGFBP-3)
      from 1930 to 3355 micrograms/l after 4 months of GH treatment (p < 0.0001). In
      addition, the molar ratio between IGF-I and IGFBP-3 increased significantly from
      0.22 to 0.33 after GH treatment (p < 0.0001). Bone alkaline phosphatase increased
      significantly from 38.6 to 92.9 U/l during GH therapy in male patients (p <
      0.0001), whereas liver-derived alkaline phosphatase was unaltered by GH. In the
      females, the increase in bone alkaline phosphatase did not reach statistical
      significance (19.1 vs 40.0 U/l, p = 0.06). The GH-induced increase in bone
      alkaline phosphatase correlated significantly with the increase in serum IGFBP-3
      (r = 0.46, p = 0.04) but not with the increase in serum IGF-I (p =
      0.16).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518731
TI  - Crossreactivity of IgE antibody against Dermatophagoides farinae with Limulus
      polyphemus agglutinin.
AB  - Crossreactivity of IgE antibody against Dermatophagoides farinae (Der f) with
      Limulus polyphemus agglutinin (LPA) was examined using RAST and immunoblot
      analysis. Of 40 Der f-sensitive asthmatic patients, 28 revealed a positive RAST
      reaction to LPA, while none of 20 Der f-insensitive hay fever patients showed
      this reaction. LPA-specific RAST levels of the 40 asthmatic patients correlated
      with their Der f-specific levels. The RAST reactivity to LPA was competitively
      inhibited by the addition of either soluble Der f or LPA, but not by the specific
      inhibitory sugar of sialic acid. LPA could also induce histamine release from
      leucocytes of Der f-sensitive asthmatic patients. IgE immunoblot analyses showed
      that the positive RAST sera for LPA had a strong IgE binding activity to the 30
      kDa and 80 kDa components of Der f body extract, whereas gel filtration studies
      showed that the high molecular weight fractions above 150 kDa retained antigenic
      constituents associated with IgE reactivity to LPA. These results suggest that
      the antigenic materials of Dermatophagoides mites share some determinants with
      the haemagglutinin of horseshoe crabs.

PMID- 7518730
TI  - The establishment and continuous subculturing of normal human adult hepatocytes:
      expression of differentiated liver functions.
AB  - The use of normal adult liver hepatocytes in cell culture for biochemical,
      toxicological and pharmacological studies has been greatly limited owing to the
      loss of replicative capacity and differentiated liver function. This is contrary
      to the ability of the liver to regenerate following injury in vivo. This suggests
      that liver "stem" or "transitional" hepatocytes exist that upon proper stimulus
      divide and differentiate into mature hepatocytes. In this study we report the
      establishment and culture of hepatocytes from normal human adult liver, which:
      (1) possess replicative capacity sufficient to subpassage 12-15 times (27-37
      cumulative population doublings); (2) can be cryopreserved for subsequent use
      without loss of replicative capacity; and (3) upon differentiation in culture
      synthesize albumin and keratin 18 and metabolize benzo[a]pyrene. The ability of
      these cells to divide or express differentiated functions appears to be due to a
      number of cellular, biochemical and physical characteristics that are present
      during the primary establishment and subsequent growth phases of the cell
      cultures. Disassociation of cells from excess liver tissue was best achieved by
      combining the mechanical action of the Stomacher with very low amounts of
      proteolytic enzymes and EGTA. The cell lines appeared to grow best when
      established and subpassaged in an mALPHA medium supplemented with insulin,
      hydrocortisone, transferrin, epithelial growth factor and fetal bovine serum
      (prescreened for human hepatocyte cell growth). The seeding density and cell-cell
      contact in culture appeared to be important for both cell division and expression
      of liver function. When cells were seeded at a low density and subpassaged before
      confluency, the cells continued to divide. Albumin and keratin 18 synthesis
      occurred primarily in tightly packed cell clusters. When cells were seeded at a
      high density, near confluency, albumin and keratin 18 synthesis occurred
      uniformly in all of the cells of the culture and the culture metabolized
      benzo[a]pyrene to water-soluble metabolites, which covalently bound to cellular
      DNA. This appearance of liver functions was consistent with the "transition" of
      hepatocytes to a terminally differentiated state. Nonhepatic markers, i.e., alpha
      fetoprotein, factor VIII and gamma-glutamyl transpeptidase activity were not
      expressed in cells cultured at either low or high density. Thus, the data
      presented here indicate that normal human adult liver hepatocytes, once
      established in culture, can be subpassaged to a high number of population
      doublings, cryopreserved for later use, and modulated to express differentiated
      liver functions.

PMID- 7518732
TI  - Clinical evaluation of erythrocytosis in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy in southeast
      Asia and sub-Saharan Africa. During its clinical course, patients may manifest a
      variety of paraneoplastic syndromes, including erythrocytosis. However, there are
      few reports on the clinical and biochemical characteristics of HCC patients who
      manifest erythrocytosis. The purpose of this study is to evaluate the incidence
      of erythrocytosis in a large series of the Chinese patients with HCC, and to
      investigate the association of erythrocytosis with tumor volume and with serum
      levels of alpha-fetoprotein (AFP) and erythropoietin. METHODS: Among 792 Chinese
      HCC patients who were seen during a 3-year period, we identified HCC patients
      with erythrocytosis as those with hemoglobin levels greater than 16.7 gm/dL (two
      standard deviations above the mean hemoglobin level of matched normal controls).
      The tumor size and serum levels of AFP and erythropoietin were evaluated in HCC
      patients with erythrocytosis to compare with HCC patients without erythrocytosis.
      RESULTS: 20 (2.5%) of 792 Chinese HCC patients presented with erythrocytosis.
      Nineteen of these 20 HCC patients were found to have either bi-lobar tumor
      involvement or a large tumor mass confined to one lobe of the liver. The
      estimated mean tumor volume of HCC patients with erythrocytosis was 50% of whole
      liver. When compared with HCC patients without erythrocytosis, the 20 HCC
      patients with high hemoglobin levels had significantly higher serum levels of AFP
      and erythropoietin (356,343 +/- 145,807 vs. 16,881 +/- 10,425 ng/mL, 135 +/- 45
      vs. 25 +/- 4 mU/mL, respectively, p < 0.01). CONCLUSIONS: Base on our findings,
      detection of erythrocytosis in a patient with HCC would indicate the presence of
      a large tumor burden, and high serum levels of both AFP and erythropoietin should
      be associated with this paraneoplastic syndrome.

PMID- 7518733
TI  - Phylogenetic studies on uncultured Frankia populations in nodules of Datisca
      cannabina.
AB  - Part of the 16S rRNA gene was amplified directly from uncultured endophyte
      populations within the root nodules of Datisca cannabina and three strains
      isolated from nodules of Alnus glutinosa (AgKG'84/4), Coriaria nepalensis (Cn3),
      and D. cannabina (Dc2). Sequence comparison based on 930 nucleotides indicated
      that the endophyte of D. cannabina nodules belongs to the genus Frankia and is
      highly related to the endophyte of C. nepalensis root nodules. The relatedness of
      the endophytes of C. nepalensis and D. cannabina nodules was also reflected by
      closely related nifH sequences amplified from the nodules. 16S rRNA sequence
      analysis of the noninfective strains obtained from both D. cannabina (Dc2) and C.
      nepalensis (Cn3) nodules also revealed the close relationship of these strains to
      the genus Frankia.

PMID- 7518735
TI  - Primary malignant mixed Mullerian tumor (metaplastic carcinoma) of the female
      peritoneum. A clinical, pathologic, and immunohistochemical study of three cases
      and a review of the literature.
AB  - BACKGROUND: Malignant mixed mesodermal tumors (malignant mixed Mullerian tumors
      [MMMT]) occur rarely in extragenital sites. METHODS: The authors analyzed the
      clinical, pathologic, and immunohistochemical features of three cases of primary
      MMMT of the female peritoneum. RESULTS: The neoplasms occurred in 60-, 64- and 84
      year-old women and arose from pelvic peritoneum. Two patients died with
      disseminated disease 8 and 24 months postoperatively. The third died of cardiac
      failure 12 months postoperatively with questionable metastatic disease.
      Microscopically, two tumors were of the heterologous type, containing foci of
      rhabdomyosarcomatous (case 1) and chondrosarcomatous (case 3) differentiation.
      Immunohistochemically, coexpression of keratin and vimentin was observed focally
      in both carcinomatous and sarcomatous components in all three neoplasms, whereas
      coexpression of low molecular weight cytokeratin, vimentin and actin was observed
      focally in case 2. Rhabdomyosarcomatous areas were positive with desmin and
      actin, and chondrosarcomatous areas for S-100 protein. Both epithelial and
      mesenchymal components were positive for alpha-1 antichymotrypsin in all cases.
      CONCLUSIONS: On the basis of the present cases and a review of 15 reports from
      the literature, primary MMMT of the female peritoneum proved to be a rare but
      highly malignant neoplasm occurring in elderly postmenopausal women. Of 15
      patients with available follow-up, 12 died with disease, mostly within 1 year,
      regardless of the initial tumor stage, histology (homologous versus heterologous
      MMMT) or treatments attempted. The tumor developed within pelvic peritoneum in
      half the cases. Histogenetically, peritoneal MMMT are thought to represent
      "metaplastic" carcinomas originating from the secondary Mullerian system.

PMID- 7518734
TI  - Periodic health examination, 1994 update: 3. Primary and secondary prevention of
      neural tube defects. Canadian Task Force on the Periodic Health Examination.
AB  - OBJECTIVE: To make recommendations on nutritional interventions and screening
      manoeuvres to prevent the birth of infants with neural tube defects (NTDs).
      OPTIONS: Folic acid consumption through diet or supplementation in women at low
      risk and at high risk of having a fetus with an NTD, and maternal serum alpha
      fetoprotein (MSAFP) screening in low-risk pregnancies. OUTCOMES: A reduction in
      the incidence rate of NTDs and potentially harmful effects of false-positive
      results of screening tests (i.e., abortion of a normal fetus). EVIDENCE: A
      MEDLINE search with the use of medical subject headings "neural tube defects,"
      "prenatal diagnosis" and "prevention and control" identified 103 original
      articles published between January 1979 and March 1993. Two reviewers extracted
      the data by applying the rules of evidence developed by the Canadian Task Force
      on the Periodic Health Examination. VALUES: The task force's evidence-based
      methods and values were used; high value was placed on prevention of NTDs and on
      limitation of the harmful effects of a pregnancy involving a fetus with an NTD.
      BENEFITS, HARMS AND COSTS: Evidence suggests that folic acid supplementation can
      decrease the incidence rate of NTDs in low-risk pregnancies by 40% to 60% with no
      adverse effects. MSAFP screening between the 16th and 18th weeks of gestation can
      reach a sensitivity of 83% and a specificity of 98% when it is used as part of an
      organized program. The effect of screening on the incidence rate of NTDs depends
      on whether affected fetuses are aborted. RECOMMENDATIONS: All women of
      childbearing age should be advised to increase their consumption of folic acid
      through diet or supplementation to 0.4 mg/d beginning 1 month before pregnancy
      and ending at the start of the second trimester. MSAFP screening is recommended
      in low-risk pregnancies only when it is part of a screening program that includes
      access to all necessary diagnostic services. High-risk women should be referred
      to genetic counselling before they plan a pregnancy. VALIDATION: These
      recommendations are comparable to the current recommendations of the US Centers
      for Disease Control and Prevention, the Society of Obstetricians and
      Gynaecologists of Canada, the Canadian Laboratory Centre for Disease Control and
      the Canadian College of Medical Geneticists, and they were validated through
      external review. SPONSOR: These guidelines were developed and endorsed by the
      Canadian task force, which funded by Health Canada.

PMID- 7518737
TI  - Maffucci's syndrome--the result of neural abnormalities? Evidence of mitogenic
      neurotransmitters present in enchondromas and soft tissue hemangiomas.
AB  - BACKGROUND: Maffucci's syndrome (MS) is distinguished by the enigmatic
      association of benign cartilaginous bone tumors and soft tissue hemangiomas.
      METHODS: This study was conducted to define the distribution of nerves and
      neuropeptides around these tumors. Results were measured by quantitative image
      analysis of immunohistochemical staining. Four types of tissues were compared:
      connective tissues around normal muscles, solitary hemangiomas, MS hemangiomas,
      and MS enchondromas (the last two from a single patient). RESULTS: The number of
      nerves was found to be quadrupled in both types of hemangiomas as compared to
      normal connective tissue. A unique feature of MS tissues is the presence of an
      increased number of nerve fibers not only in the lesions but also in
      histologically normal margins of resection surrounding the lesions. Furthermore,
      hemangiomas of both types were found to contain a significantly higher number of
      calcitonin gene-related peptide-, substance P-, and methionine enkephalin
      positive fibers than did normal muscle or its related fibroconnective tissue.
      These neuropeptides are mitogens, and their presence stimulates the growth of the
      abnormal blood vessels. Enchondroma fragments from an MS patient contained
      numerous methionine enkephalin-positive nerves. This neuropeptide is known to act
      as a growth factor in cartilage proliferation. CONCLUSIONS: A neural abnormality
      of the neuropeptidergic nervous system seems to relate to the abnormal tumors
      seen in MS.

PMID- 7518736
TI  - Characterization and functional analysis of the expression of vascular adhesion
      molecules in human papillomavirus-related disease of the cervix.
AB  - BACKGROUND: Cervical intraepithelial neoplasia (CIN) is associated with changes
      in local immune cell populations, although the role of vascular adhesion
      molecules in mediating such changes by controlling the traffic of mononuclear
      cells to the cervix has not been investigated previously. METHODS: The authors
      used immunohistochemistry to examine the expression of three vascular adhesion
      molecules--ICAM-1, VCAM-1 and E-selectin--in the normal cervix and in biopsies of
      CIN Grade 1 (CIN-1) (low grade squamous intraepithelial lesions [LG-SIL]) and CIN
      2/3 (high grade squamous intraepithelial lesions[HG-SIL]). In addition, the
      authors examined the functional role of these molecules by adapting the frozen
      section adhesion assay of Stamper and Woodruff to investigate in vitro the
      molecular basis of the interaction between cervical endothelial cells and
      activated T-lymphocytes. RESULTS: Whereas there was no difference in adhesion
      molecule expression between normal cervix and CIN-1 (LG-SIL), all three molecules
      investigated were significantly up-regulated in CIN-2/3 (HG-SIL), an observation
      that correlated with an enhanced ability of stromal endothelial cells in CIN-2/3
      (HG-SIL) biopsies to bind activated peripheral blood lymphocytes in vitro.
      Monoclonal antibodies blocking ICAM-1 function were able to reduce such adhesion
      significantly in three of three experiments, and antibodies blocking VCAM-1
      produced a significant reduction in one of three experiments. No inhibition was
      seen with antibodies against E-selectin. CONCLUSIONS: The enhanced expression of
      vascular adhesion molecules in CIN-2/3 (HG-SIL) appears to be functionally
      important in enabling the local recruitment of immunocompetent cells and supports
      the notion of a local antineoplastic immune response in high grade cervical
      intraepithelial lesions.

PMID- 7518738
TI  - Stromelysin-3 in stromal tissue as a control factor in breast cancer behavior.
AB  - BACKGROUND: It has long been proposed that secreted proteinases, including the
      matrix metalloproteinases, play an important part in tumor progression in
      mediating extracellular matrix remodeling. More recently, it has been suggested
      that extracellular proteinases also regulate growth factors and cytokines that
      may contribute to tumor progression. METHODS: RNA in situ hybridization and
      immunohistochemistry were used to study the expression, in breast and other types
      of human carcinomas, of the stromelysin-3 (ST3) gene, which encodes a putative
      new member of the matrix metalloproteinase family. RESULTS: The ST3 gene is
      overexpressed in most types of human carcinomas, including breast carcinoma where
      ST3 RNA was detected in 95% (99 of 104) of invasive primary tumors. Both ST3
      protein and RNA are detected in fibroblastic cells immediately surrounding the
      cancer cells, but not in the malignant cells or in stromal cells at a distance
      from them. The ST3 gene also is expressed in some in situ breast carcinomas,
      where ST3 expression correlates with the known risk of these tumors to become
      invasive. CONCLUSIONS: ST3 is the paradigm of tumor proteinases that are not
      expressed in the malignant cells of human carcinomas but in fibroblastic cells of
      tumor stroma. ST3 represents a potential new prognostic parameter to identify
      subpopulations of aggressive tumors, particularly to evaluate the likelihood of
      in situ breast carcinoma progression to invasive cancer. Furthermore, the
      specific expression of the ST3 gene in fibroblastic cells immediately surrounding
      cancer cells suggests that ST3 may be involved in tumor progression and that it
      represents a potential target for cancer treatment.

PMID- 7518739
TI  - Convergent synthesis of an octasaccharide fragment of the O-specific
      polysaccharide of Shigella dysenteriae type 1.
AB  - A stereocontrolled, convergent synthesis is described of the linear
      octasaccharide methyl glycoside alpha-L-Rha p-(1-->2)-alpha-D-Gal p-(1-->3)-alpha
      Glc p NAc-(1-->3)-al pha-L-Rha p-(1-->3)-alpha-L-Rha p-(1-->2)-alpha-D-Gal p-(1-
      >3) -alpha-D-Glc p NAc-(1-->3)-alpha-L-Rha p-OMe (11), which corresponds to two
      contiguous repeating units of the O-specific polysaccharide of Shigella
      dysenteriae type 1.

PMID- 7518740
TI  - Structure of the capsular antigen of Escherichia coli O8:K50:H-.
AB  - The primary structure of the acidic capsular antigen of Escherichia coli O8:K50:H
      was shown by glycose analysis, methylation analysis, and one- and two
      dimensional 1H and 13C NMR spectroscopy to be composed of repeating linear
      tetrasaccharide units having the structure: (formula: see text).

PMID- 7518741
TI  - 2-Acetamido-4-O-[(S)-1-carboxyethyl]-2-deoxy-D-glucose: a new natural isomer of N
      acetylmuramic acid from the O-specific polysaccharide of Proteus penneri 35.

PMID- 7518742
TI  - Fluorination at position 6 of derivatives of methyl alpha-D-galactopyranoside.

PMID- 7518743
TI  - Somatic antigens of pseudomonads: structure of the O-specific polysaccharide of
      Pseudomonas fluorescens biovar A strain IMV 472.

PMID- 7518744
TI  - The structure of the O-specific polysaccharide of Pseudomonas solanacearum strain
      8089.

PMID- 7518745
TI  - Synthesis of specifically monofluorinated ligands related to the O-polysaccharide
      of Shigella dysenteriae type 1.
AB  - The synthesis is reported of galactopyranose nucleophiles monofluorinated at
      positions 3, 4, or 6 and protected by 4,6-O-benzylidene, 3,6-di-O-benzyl, or 3,4
      O-isopropylidene groups, respectively. The condensation of these nucleophiles
      with 2,3,4-tri-O-benzoyl-alpha-L-rhamnosyl bromide gave, after deprotection, the
      disaccharide analogues of methyl O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-D
      galactopyranoside, monofluorinated at position 3, 4, or 6 of the galactoside
      residue.

PMID- 7518746
TI  - The structure of the O-specific polysaccharide of Salmonella arizonae O21
      (Arizona 22) containing N-acetylneuraminic acid.
AB  - The O-specific polysaccharide of S. arizonae O21 was found to contain 2-acetamido
      2-deoxy-D-glucose, 2-acetamidino-2,6-dideoxy-L-galactose, N-acetylneuraminic
      acid, and O-acetyl groups. On the basis of 1H and 13C NMR studies of the intact
      and O-deacetylated polysaccharide and oligosaccharide fragments obtained by
      solvolysis with anhydrous hydrogen fluoride, partial methanolysis and partial
      hydrolysis, it was concluded that the O-specific polysaccharide has the following
      structure: [formula: see text]

PMID- 7518747
TI  - The structure of the O-specific polysaccharide of Hafnia alvei strain 1216.
AB  - The O-specific polysaccharide of Hafnia alvei strain 1216 is composed of D
      galactose, D-glucuronic acid, 2-acetamido-2-deoxy-D-glucose, 3,6-dideoxy-3-[(R)-3
      hydroxybutyramido]-D-glucose, and O-acetyl groups in the ratios 1:1:2:1:1. On the
      basis of sugar and methylation analyses of the intact and chemically degraded (O
      deacetylated, carboxyl-reduced, Smith-degraded) polysaccharide and 1H and 13C NMR
      spectroscopy, including 2D shift-correlated (COSY, relayed COSY, 13C, 1H-COSY)
      and 1D NOE spectroscopy, it was concluded that the O-antigen is built up of
      linear pentasaccharide units having the following structure: [formula: see text]

PMID- 7518748
TI  - Fine specificity of T cell lines and clones that are capable of inducing
      autoimmune manifestations in mice.
AB  - Myasthenia gravis is a T-cell-regulated, antibody-mediated autoimmune disease.
      The synthetic peptides p195-212 and p259-271, which represent sequences of the
      human acetylcholine receptor alpha-subunit, preferentially stimulated T cells of
      patients with myasthenia gravis and were found to be immunodominant T cell
      epitopes in SJL and BALB/c mice, respectively. Therefore, we established a p195
      212-specific T cell line from SJL mice and a p259-271-specific T cell line from
      BALB/c mice. N- and C-terminal truncated and/or extended peptides differed in
      their ability to stimulate proliferative responses of the lines and of their
      derived clones. Activated cells of the lines were inoculated into naive syngeneic
      mice. In both strains of mice, peptide-specific antibodies and antibodies to the
      murine acetylcholine receptor were detected. In addition, decremental compound
      muscle action potentials consistent with impairment of neuromuscular transmission
      were recorded from the line-inoculated mice. Thus, these T cell lines, clones,
      and epitopes constitute a useful model for investigating T cell pathogenicity in
      autoimmune manifestations related to myasthenia gravis.

PMID- 7518749
TI  - Steel factor (c-kit ligand) stimulates the in vitro growth of immature CD3-/CD4
      /CD8- thymocytes: synergy with IL-7.
AB  - The ability of Steel factor (SLF) to stimulate the growth of immature thymocytes
      alone and in combination with IL-7 was assessed. In suspension cultures of CD4
      /CD8- thymocytes, SLF itself did not induce significant proliferation, but in
      combination with IL-7, it induced a greater response than did IL-7 alone. In
      fetal thymus lobe submersion cultures, SLF stimulated the growth of cells to a
      magnitude similar to that of IL-7 and the combination resulted in a synergistic
      response. Phenotypic analysis of these cells revealed that SLF in comparison to
      IL-7 stimulated the growth of a less mature population. The synergistic growth
      stimulated by the combination of IL-7 and SLF occurred in a population of IL
      2R+/CD4-/CD8-/CD3- cells. Cells grown in SLF expressed low levels of IL-2R and
      overnight culture in IL-7 dramatically increased IL-2R expression. Thus, these
      results are consistent with the hypothesis that SLF stimulates the growth of a
      less mature thymocyte population than does IL-7.

PMID- 7518750
TI  - Induction of the nitric oxide-synthesizing pathway in fresh and interleukin 2
      cultured rat natural killer cells.
AB  - Several lines of evidence suggest that nitric oxide (NO), generated through
      nitric oxide synthase (NOS) by cleavage of terminal guanidino nitrogen from L
      arginine, mediates tumor cell killing by mononuclear phagocytes. Natural killer
      (NK) cells are cytotoxic effector cells that lyse a variety of tumor and virus
      infected cells in a MHC-unrestricted manner. NK cells cultured with interleukin 2
      proliferate and acquire the ability to lyse a wide range of targets, including NK
      resistant tumor cells (LAK activity). The present study was designed to
      investigate whether a NOS pathway exists in fresh or IL-2-activated NK cells and
      to assess the importance of NO synthesis in their activation and cytotoxic
      functions. NKR-P1 triggering, which is known to induce NK cell activation and
      mediate reverse ADCC, was able to induce arginine metabolism with consequent
      increase of nitrite and citrulline levels. Moreover, stimulated NO synthesis
      leads to guanylate cyclase activity with consequent cGMP generation. We also
      report that cytotoxic activities of fresh or IL-2-activated NK cells appear to be
      dependent on arginine levels in medium. Tumoricidal activity of both these
      effector cells, assessed against YAC-1 and P815 target cells, respectively, was
      indeed significantly reduced when cytotoxic assays were performed in arginine
      free medium or in the presence of the L-arginine analog L-N-monomethyl-arginine,
      which inhibits nitroxide formation from L-arginine. Normal levels of cytotoxic
      activities could be restored by addition of exogenous L-arginine. NO generation
      by NK and LAK cells, determined as nitrite, citrulline, and cGMP synthesis,
      correlated well with their cytotoxic activities. Moreover, NOS activity gradually
      increased during the LAK generation and correlated well with the increasing
      capability of IL-2-activated NK cells to lyse NK-resistant targets, such as P815.

PMID- 7518751
TI  - Immune responses, and autoimmune outcome, during virus infection of the central
      nervous system.
AB  - A combined role of a virus infection of the central nervous system (CNS) and an
      autoimmune response to myelin basic protein (MBP), an autoantigen of the CNS, is
      suggested in the pathogenesis of multiple sclerosis (MS). SJL mice are highly
      susceptible while B6 mice are less susceptible to the induction of experimental
      autoimmune encephalomyelitis (EAE), the autoimmune model of MS. Peripheral
      inoculation of Semliki forest virus (SFV) into SJL and B6 mice resulted in: (1)
      Higher viral titers, more severe clinical disease, and hence a stronger
      nonspecific and SFV-specific lymphoproliferation, and production of IFN-gamma and
      TNF/LT was observed by splenocytes (SPL) of B6 than by those of SJL mice, on Day
      7 postinfection. (2) Following viral clearance, however, proliferation to SFV,
      and to MBP, and the production of IFN-gamma and TNF/LT by SPL of SFV-infected SJL
      mice were significantly higher, while the production of TGF-beta was
      significantly lower than by those of B6 mice. In conclusion, the immune responses
      to SFV, and to MBP, which were triggered by SFV infection were significantly
      higher and more prolonged in the SPL of SJL mice, the EAE-susceptible mice, than
      by those of B6 mice after the infection was cleared.

PMID- 7518752
TI  - Epitope specificity and T cell receptor usage in type II collagen induced
      autoimmune ear disease.
AB  - An immune response directed against type II collagen (CII) has been reported in
      several autoimmune diseases including the animal models of collagen-induced
      arthritis (CIA) and collagen-induced autoimmune ear disease (CIAED). In this
      communication, we have found that T cells from type II collagen-immunized DBA/1
      lac could transfer auricular chondritis to naive mice. The T cells from type II
      collagen-immunized H-2r and H-2q mice recognize different epitopes from the CB11
      peptide of CII. The CII-specific T cells from H-2q background mice recognize
      peptide residues p121-147 (P1) but do not respond to residues p211-247 (P2). The
      T cells of H-2r mice immunized with CII respond better to P2 rather than P1. By
      altering certain amino acids within these epitopes, the response of CII-specific
      TCR to antigen has been increased or abolished. Our results suggest that the
      lysine residues at positions 129, 141, and 147 in P1, the arginine residue at
      position 227, and glutamic acid at position 230 in P2 might play an important
      role in the trimolecular interaction. Ten clonally distinct T cell hybridomas
      specific for CII have been established from H-2r B10.RIII mice and the beta
      chains of their TCR have been analyzed. Three subfamilies, V beta 1, V beta 6,
      and V beta 8, were utilized with dominant expression of V beta 8 (60%). This is
      quite similar to the pattern found in type II collagen-induced arthritis in H-2q
      mice. This preferential use of V beta 8 in CIAED implies that an immunotherapy
      may make it possible to control this autoimmune disease, even in a MHC-diverse
      situation.

PMID- 7518753
TI  - Suppression of collagen-induced arthritis using an angiogenesis inhibitor, AGM
      1470, and a microtubule stabilizer, taxol.
AB  - Collagen-induced arthritis (CIA) is a T-cell-dependent rat model of rheumatoid
      arthritis (RA) that is induced by injection of collagen type II in incomplete
      Freund's adjuvant. Neovascularization within the synovium is a prominent feature
      of CIA and RA. The novel angiogenesis inhibitor AGM-1470 and the microtubule
      stabilizing agent Taxol represent two new classes of agents with specific
      mechanisms of action. AGM-1470 inhibits fibroblast growth factor-induced
      stimulation of endothelial cell migration, endothelial cell proliferation, and
      capillary tube formation, resulting in effective suppression of new blood vessel
      formation. By enhancing microtubule polymerization, Taxol interferes with normal
      microtubule function in cell mitosis, migration, chemotaxis, and intracellular
      transport. Using a suppression protocol in established CIA, the effects of AGM
      1470 and Taxol as single agents and in combination were evaluated. Combination
      therapy significantly reduced clinical arthritis compared to control rats (P <
      0.00001). The combination therapy group also experienced earlier and
      significantly greater reduction of clinical arthritis compared to either single
      agent-treated groups (P < 0.05). Blinded radiographic scores at the end of the
      study demonstrated less soft tissue swelling and joint destruction using
      combination therapy than either single agent. This is the first use of AGM-1470
      and Taxol in combination therapy. Further study of agents with distinct
      mechanisms of action may lead to more effective treatment options in chronic
      inflammatory arthritis and to a better understanding of the pathophysiologic
      processes of pannus formation.

PMID- 7518754
TI  - The CD28/B7 pathway costimulates the response of primary murine T cells to
      superantigens as well as to conventional antigens.
AB  - While the CD28/B7 pathway has been shown to play an important costimulatory role
      in the response of T cells to conventional antigens, its role in superantigen
      mediated T cell activation has not been as clear. In this report, we used CD4+ T
      cells from ovalbumin-specific alpha beta-TCR-transgenic mice (DO11.10) to compare
      the ability of this pathway to costimulate the response of primary T cells to
      conventional antigens and superantigens. We show that either the addition of anti
      CD28 monoclonal antibody or presentation with a B7 transfected cell line enhances
      the proliferative and interleukin-2 secretion response of DO11.10 CD4+ cells to
      both the conventional antigen, ovalbumin peptide (OVA 323-339), and the
      superantigen SEB. This implies that CD28-mediated costimulation plays a role in
      the response of murine T cells to superantigens as well as to conventional
      antigens.

PMID- 7518755
TI  - CD54/ICAM-1 is a costimulator of NK cell-mediated cytotoxicity.
AB  - The receptors and the array of cell adhesion molecules regulating MHC
      unrestricted cytotoxic activity of NK cells toward tumor targets have not
      completely characterized. Antibody inhibition studies suggest roles for a number
      of cell adhesion molecules (CAMs). Recent studies suggest that CAMs can function
      to stabilize cell-to-cell interactions and/or to provide costimulatory signals
      that are crucial for T cell activation. It has been difficult to experimentally
      demonstrate that adhesion molecules also function as costimulators in NK cell
      mediated cytotoxicity. We have developed an experimental system using cells
      transfected with genes encoding huICAM-1 and/or LFA-3 to investigate the function
      of adhesion molecules. Here we report that neither the expression of transfected
      ICAM-1 or LFA-3 alone nor the expression of both ICAM-1 and LFA-3, in the absence
      of MHC class I molecules, converts a murine cell line that is resistant to NK
      cell-mediated lysis into a susceptible one. We next tested the ability of ICAM-1
      or LFA-3-mediated interactions to provide costimulation of NK cell cytolytic
      activity using a "three cell" experimental system comprising human NK cells, 51C
      labeled target cells, and transfected mouse cells as a source of costimulation.
      The ability of NK cells to lyse K562 cells or anti-CD16-coated target cells was
      significantly enhanced by the addition of ICAM-1-transfected cells, whereas the
      addition of cells transfected with LFA-3 or irrelevant genes did not enhance
      lytic activity. Since the transfected huICAM-1 interacts with NK cells at sites
      spatially separate from the NK cell-target cell interactions, our data suggest
      that LFA-1-ICAM-1 or MAC-1-ICAM-1 interactions can provide remote costimulation,
      via signaling events, to induce cytotoxic activity in NK cells.

PMID- 7518756
TI  - Rat aortic smooth muscle cells expressing charybdotoxin-sensitive potassium
      channels exhibit enhanced proliferative responses.
AB  - 1. The relationship between the expression of potassium (K+) channels and the
      growth properties of cultured vascular smooth muscle cells was examined. 2. Two
      groups of cells having different proliferative rates were cultured from the
      Wistar-Kyoto rat aorta. One group of cells, derived from early passages (3-5),
      proliferated with a cell doubling time of 2.41 days. A second group of cells,
      derived from late passages (> 12), proliferated at a higher rate (cell doubling
      time, 0.61 days). 3. Exposure of the early passaged cells to endothelin-1 (0.1
      mumol/L) induced membrane depolarization. In contrast, exposure of the late
      passage cells to endothelin-1 (0.1 mumol/L) evoked a rapid hyperpolarization. The
      hyperpolarization in the late passage cells was blocked by charybdotoxin (20
      nmol/L), an inhibitor of the large-conductance Calcium (Ca)-activated K+ channel.
      4. The authors conclude that rapidly proliferating vascular smooth muscle cells
      express enhanced activity of Ca-activated K+ channels causing marked alterations
      in the electrical properties of the cells. It is therefore suggested that the
      reported increase in Ca-activated K+ channel activity in the aortae of
      hypertensive rats is likely to be associated with the increased proliferative
      ability of the vascular smooth muscle cells.

PMID- 7518757
TI  - Effect of transforming growth factor-beta 1 on platelet-derived growth factor
      receptor binding and gene expression in vascular smooth muscle cells from SHR and
      WKY rats.
AB  - 1. This study examined the effects of transforming growth factor-beta 1 (TGF-beta
      1) on platelet-derived growth factor-BB (PDGF-BB)-stimulated DNA synthesis,
      [125I]-PDGF-BB receptor binding and PDGF-beta receptor mRNA expression in
      vascular smooth muscle cells (VSMC) isolated from Wistar-Kyoto (WKY) rats and
      spontaneously hypertensive rats (SHR). 2. TGF-beta 1 inhibited by 40% DNA
      synthesis stimulated by PDGF-BB in VSMC from WKY rats but potentiated by 20%
      growth factor-stimulated DNA synthesis in VSMC from the SHR. 3. Since the
      difference in effect of TGF-beta 1 could not be attributed to differential
      regulation of [125I]-PDGF-BB binding activity and PDGF-beta receptor mRNA
      expression, it is suggested that alterations in intracellular signalling pathways
      may account for the differential effects of TGF-beta 1 on PDGF-BB-stimulated DNA
      synthesis in VSMC from SHR and WKY rats.

PMID- 7518759
TI  - Type II collagen expression in small, biopsy-sized samples of cartilage using a
      new method of RNA extraction.
AB  - The extraction of mRNA from cartilage samples is complicated by the presence of
      proteoglycans and the low cellular density of the tissue. We required a method
      that would enable mRNA to be extracted from small biopsy-sized samples of
      cartilage. The method had to produce consistent results and sufficient RNA for
      Northern and PCR analysis. Methods of total RNA extraction, previously shown to
      be effective for cartilage, were compared with a new technique in which an oligo
      (dT) conjugated to biotin hybridises to the mRNA. The hybrids are captured with
      covalently coupled streptavidin paramagnetic particles. Samples of growth plate
      cartilage, including those specifically from the upper (proliferative and
      transitional) and lower (fully hypertrophic) zones, were collected and some were
      frozen at -70 degrees C. Samples for extraction by the paramagnetic method
      weighed approximately 80 mg and approximately 12 micrograms of mRNA was extracted
      from fresh tissue samples. The yield from similar frozen samples of the same
      weight was about a seventh of that from the fresh tissues. 5 micrograms of the
      mRNA from each sample was run on a gel, and a Northern blot was prepared and
      probed with a [32P]-labelled antisense RNA probe to type II collagen cDNA. A
      distinct band of type II collagen mRNA was detected (5.3 Kb) in the samples from
      the upper (proliferative and transitional) zone. The traditional methods of
      extracting RNA from cartilage required far greater quantities of tissue and the
      RNA produced was frequently degraded. The results obtained using the paramagnetic
      bead method precluded further trials with modification of the traditional methods
      of mRNA extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518758
TI  - Human autoantibody production in the severe combined immunodeficiency (scid)
      mouse.
AB  - We investigated the production of autoantibodies in severe combined
      immunodeficient (scid) mice that received an intraperitoneal injection of
      peripheral blood mononuclear cells (PBMC) from patients with systemic lupus
      erythematosus. Mice receiving 50 x 10(6) cells consistently engrafted, as
      evidenced by the presence of human immunoglobulin in the hu-PBL-scid serum;
      though none, any one, or a combination of the autoantibody specificities found in
      the donor could be found in the hu-PBL-scid serum. Production of anti-Ro antibody
      in the hu-PBL-scid chimeric mice could be enhanced by treatment with the Ro
      antigen. These results indicate that not only can scid mice engrafted with PBMC
      from patients with SLE produce autoantibody, but also that this production can be
      manipulated with specific antigen.

PMID- 7518760
TI  - A novel in vitro assay system for transendothelial tumor cell invasion:
      significance of E-selectin and alpha 3 integrin in the transendothelial invasion
      by HT1080 fibrosarcoma cells.
AB  - The interaction of tumor cells with endothelial cells is a key event in tumor
      metastasis. We established an in vitro invasion assay system, in which the
      invasion of tumor cells after interaction with endothelial cells can be examined.
      Two chamber culture wells separated by porous membrane were used. Human umbilical
      vein endothelial cells (HUVEC) were placed on porous membranes coated with matrix
      components. The invasion by HT1080 fibrosarcoma cells was determined in this
      system by counting the number of cells that moved through the membranes from
      upper to lower chambers. HUVEC cells did not migrate through the membranes as
      judged by the staining with UEA-I. Observation by scanning electron microscopy
      revealed that HT1080 cells bound to HUVEC surfaces and migrated underneath the
      HUVEC monolayer. Effects of antibodies specific for cell surface adhesion
      molecules on the migration of HT1080 cells were examined. Invasion of uncoated
      membranes and membranes coated with HUVEC cells was compared. Antibody against E
      selectin significantly suppressed an increase of HT1080 cell invasion of HUVEC
      monolayers stimulated by IL-1 beta or TNF alpha. Antibody against integrin alpha
      3 subunit remarkably inhibited the invasion of HUVEC cell-coated membranes,
      suggesting that integrins with the alpha 3 subunit may play an important role in
      the transendothelial invasion by HT1080 cells.

PMID- 7518761
TI  - Stability in the presence of widespread beta-lactamases. A prerequisite for the
      antibacterial activity of beta-lactam drugs.
AB  - Bacterial resistance to the beta-lactam drugs is extremely widespread, as a
      result of extensive drug use. Loss of susceptibility is primarily attributable to
      hydrolysis by inactivating enzymes, namely the beta-lactamases. While the number
      of characterised beta-lactamases may exceed 100, only a few are a problem in the
      treatment of community-acquired infections (TEM-1, TEM-2, SHV-1, BRO-1).
      Chromosomally mediated and extended-spectrum beta-lactamases are usually dominant
      in nosocomial pathogens where oral antibiotic therapy is seldom used. Therefore,
      the threat posed by beta-lactamases must be considered in general practice.
      Several effective strategies have been implemented in order to overcome beta
      lactamase-mediated resistance, e.g. use of non-beta-lactam drugs or beta
      lactamase inhibitors. Another option has been the development of new beta-lactam
      compounds that possess a high intrinsic stability against the hydrolytic action
      of common beta-lactamases. Among these compounds, the oral third generation
      cephalosporins represent an important breakthrough. Cefetamet pivoxil, a new oral
      third generation cephalosporin, is characterised by excellent antimicrobial
      potency against Enterobacteriaceae, and Moraxella (Branhamella) catarrhalis and
      Haemophilus influenzae, irrespective of their ability to produce beta-lactamases.
      The Gram-positive respiratory pathogens, Streptococcus pyogenes and penicillin
      susceptible S. pneumoniae, are also satisfactorily covered. The activity of
      cefetamet has recently been corroborated in a survey conducted in Italy involving
      4191 isolates. However, cefetamet shows no activity against enterococci,
      staphylococci, Listeria, alpha-streptococci, Pseudomonas, Acinetobacter and
      anaerobes. Given this antibacterial profile, cefetamet pivoxil may provide a
      useful alternative to other oral antibacterial agents in the empirical therapy of
      acute community-acquired respiratory and urinary tract infections. From the
      results of the Italian survey, cefetamet emerged as the only agent among those
      considered (which included cefuroxime, cefaclor, cefalexin, cefadroxil,
      ampicillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, doxycycline,
      erythromycin and clindamycin) that might be selected as the drug of choice in the
      empirical therapy of outpatient infections.

PMID- 7518762
TI  - Comparative pharmacokinetics of the new oral cephalosporins.
AB  - The comparative pharmacokinetics of the new oral cephalosporins (ester and
      nonester types), together with that of the first generation carbacephem,
      loracarbef, are considered in healthy volunteers. Also in this review,
      pharmacokinetic and microbiological data are combined in order to predict the
      possible clinical efficacy of this group of agents. Despite apparent similarities
      in the structure of these agents, single dose studies have revealed marked
      differences in the pharmacokinetics of the oral cephalosporins. Multiple dose
      studies showed no evidence of accumulation with these agents. In the elderly,
      only minor changes in the pharmacokinetics of the oral agents were observed, and
      were insufficient to warrant dosage adjustment. Unlike that of the nonester
      compounds, the bioavailability of the ester cephalosporins is increased when they
      are administered after food. Variable effects are observed when the ester agents
      are coadministered with antacids or H2-antagonists; while the absorption of
      cefetamet pivoxil was unaffected by coadministered antacids or H2-antagonists,
      the absorption of cefpodoxime proxetil was reduced.

PMID- 7518763
TI  - Cefetamet pivoxil vs cefaclor in the treatment of acute otitis media in children.
AB  - 74 children with acute otitis media (AOM) were entered into an observer-blind
      randomised multicentre general practice study to compare the efficacy and safety
      of the new third generation oral cephalosporin, cefetamet pivoxil, at a dose of
      10 mg/kg twice daily with the efficacy and safety of cefaclor 10 mg/kg twice
      daily administered for 10 days. Of 36 evaluable patients in the cefaclor
      treatment group, 28 (78%) were cured, and a further 4 were improved, giving an
      overall efficacy rate (cure/improvement) of 89%. Of 36 evaluable patients in the
      cefetamet pivoxil treatment group, 31 (86%) were cured, and a further 4 were
      improved, giving an overall efficacy rate of 97%. Adverse events were reported in
      4 patients: 1 cefaclor recipient and 3 patients in the cefetamet pivoxil
      treatment group. Diarrhoea, the most frequently observed adverse event, occurred
      in both treatment groups. The study results indicate that cefetamet pivoxil and
      cefaclor appear to have similar efficacy and safety in the treatment of AOM in
      children.

PMID- 7518764
TI  - Cefetamet pivoxil in the treatment of pharyngitis/tonsillitis in children and
      adults.
AB  - Between 15 and 35% of pharyngeal infections are attributable to Group A beta
      haemolytic streptococci. Streptococcal pharyngitis is one of the most common
      infections in adolescents and children. A specific diagnosis of pharyngitis can
      be obtained only by isolating organisms in culture. The current treatment of
      choice for streptococcal pharyngitis/tonsillitis is a 10-day course of
      phenoxymethylpenicillin (penicillin V); however, unresolved problems concerning
      the use of penicillin include the timing of therapy, appropriate therapy for
      treatment failures, chronic carriers and those with frequent recurrences. In
      addition, failure rates of 10 to 35% have been reported with oral
      phenoxymethylpenicillin. Effective treatment alternatives in this indication
      include oral cephalosporin agents or penicillin/beta-lactamase inhibitor
      combinations. The oral cephalosporins offer the advantage of an improved
      pharmacokinetic profile, once- or twice-daily administration, a shorter (7-day)
      regimen, and a low incidence of adverse effects, although these advantages must
      be balanced against the broad spectrum of these agents (broader than is
      necessary) and their cost. Clinical trials conducted with cefetamet pivoxil, a
      new oral third generation cephalosporin, in both adults and children with
      pharyngitis/tonsillitis indicate that this agent offers an effective alternative
      for phenoxymethylpenicillin in this indication.

PMID- 7518765
TI  - Comparative clinical efficacy of cefetamet pivoxil in lower respiratory tract
      infection.
AB  - Cefetamet pivoxil, because of its activity against respiratory pathogens and its
      pharmacokinetic behaviour, is expected to have clinical efficacy in the treatment
      of lower respiratory tract infection (LRTI). This paper presents an overview of
      clinical trials conducted worldwide to investigate the efficacy and tolerability
      of cefetamet pivoxil in the treatment of adults and children with LRTI. A total
      of 626 adult patients, the majority of whom presented with exacerbations of
      chronic bronchitis (n = 500), received oral cefetamet pivoxil 500 or 1000mg twice
      daily for 5 to 10 days (n = 351) or a standard comparator agent (n = 275). The
      comparator agents were amoxicillin (750mg 3 or 4 times daily, or 1000mg twice
      daily), amoxicillin/clavulanic acid (625mg 3 times daily), or cefaclor (250 or
      500mg 3 times daily) administered for 5 to 12 days. A satisfactory clinical
      outcome (cure + improvement) was achieved in 79 to 94% of evaluable patients. In
      336 children, 240 received cefetamet pivoxil at 2 dosage levels (10 or 20 mg/kg
      twice daily) for 7 to 12 days and 96 received the standard comparator, cefaclor
      (10 mg/kg 3 times daily). Cefetamet pivoxil was clinically effective at both
      dosages, and did not differ significantly compared with cefaclor (clinical cure
      rates of 97 to 99% with cefetamet pivoxil and 96% with cefaclor). A separate
      analysis of 305 patients with community-acquired pneumonia showed clinical
      successes in 80 to 100% of adults, 75 to 78% of elderly patients, and 98% of
      children treated with cefetamet pivoxil.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518766
TI  - Parenteral-oral switch in the management of paediatric pneumonia.
AB  - In phase I of a 2-phase study, 56 evaluable children (0.8 to 5 years) with lobar
      or segmental pneumonia received intravenous or intramuscular ceftriaxone 50
      mg/kg/day for 2 days followed by oral cefetamet pivoxil 20 mg/kg/day in 2 divided
      doses to complete 7 days of treatment. All patients achieved a clinical cure. In
      phase II, a randomised open multicentre study, 62 children with pneumonia
      received an identical regimen to phase I (arm A), and 59 children received
      ceftriaxone 50 mg/kg/day for 1 day followed by 6 days' treatment with cefetamet
      pivoxil 20 mg/kg/day (arm B). Patients from phase I and arm A were combined
      giving a total of 118 evaluable patients in arm A. At the end of treatment, 100%
      of patients in arm A and 96% in arm B achieved a clinical cure; cure was
      maintained in 99 and 98% of patients, respectively. Two (4%) patients in arm B
      failed therapy; in both cases, factors other than treatment failure may have
      accounted for the poor response. 11 and 12% of patients in treatment arms A and
      B, respectively, experienced adverse events; gastrointestinal events (nausea
      and/or vomiting) were reported in 9 and 8% of patients, respectively. In
      conclusion, 1 or 2 days' treatment with parenteral ceftriaxone before switching
      to oral cefetamet pivoxil was safe and effective in the treatment of childhood
      pneumonia. Therefore, parenteral-oral switch is a feasible treatment option in
      the treatment of serious paediatric community-acquired pneumonia.

PMID- 7518768
TI  - New antiepileptic drug development.
AB  - The development of new antiepileptic drugs is poised on the cusp between
      empiricism and the rational scientific development of medicaments designed to
      perform specific neurophysiologic functions in keeping with modern ideas of
      epilepsy generation and spread. It takes into account the difference between
      seizures and their underlying disorder known as epilepsies and the fact that,
      although seizures can be effectively treated with pharmacologic agents, the
      development of epilepsy requires both a predisposition (which may be innate or
      preventable) and precipitating factors that determine the timing of the
      individual seizures. The local membrane phenomena or cellular substrates of
      epilepsy can be described, as can the process of epileptogenesis. New
      antiepileptic development can be viewed in the light of these concepts.

PMID- 7518769
TI  - Dextromethorphan: cellular effects reducing neuronal hyperactivity.
AB  - Dextromethorphan is a dextrorotary morphinan without affinity for opioid
      receptors, commonly used as an antitussive medication. During the past 5 years,
      interest in the compound and its demethylated derivative, dextrorphan, has been
      revived because additional neuroprotective and antiepileptic properties were
      found in in vitro studies, animal experiments, and a few clinical cases. Both
      morphinans are able to inhibit N-methyl-D-aspartate (NMDA) receptor channels and
      voltage-operated calcium and sodium channels with different potencies. The
      inhibition of the NMDA receptor is believed to be the predominant mechanism of
      action responsible for the anticonvulsant and neuroprotective properties of the
      compounds.

PMID- 7518770
TI  - Effects of NMDA- and AMPA-receptor antagonists on different forms of epileptiform
      activity in rat temporal cortex slices.
AB  - Lowering extracellular magnesium induces different patterns of epileptiform
      activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform
      discharges in the hippocampus are stable over time, whereas seizure-like events
      (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex
      develop into late recurrent discharges which are not blocked by clinically
      employed antiepileptic drugs. We tested the sensitivity of the different
      epileptiform discharge patterns to N-methyl-D-aspartate (NMDA)- and non-NMDA
      receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ketamine,
      and 2-aminophosphonovalerate (2APV); as alpha-amino-3-hydroxy-5-methyl-4
      isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline
      derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings
      show that the different patterns of epileptiform activity, including the late
      recurrent discharges, are sensitive to all NMDA-receptor antagonists. However,
      when dextrorphan was employed to suppress seizure-like events, later recurrent
      discharges did not develop during the remaining time course of the experiment.
      CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in
      the entorhinal cortex. However, late recurrent discharges become insensitive to
      CNQX, even at a high concentration of 60 microns. This finding suggests a
      prominent role for NMDA receptors in the generation of late recurrent discharges.

PMID- 7518767
TI  - Strategies for the development of drugs for pharmacoresistant epilepsies.
AB  - Presently, most strategies for development of antiepileptic drugs (AEDs) center
      around seizure models that are known to respond to presently marketed AEDs. These
      strategies do not take into account that epilepsy can be a progressive disease.
      Moreover, region-specific aspects of epileptogenesis are rarely considered when
      new AEDs are developed. Seizures in the temporal lobe are often difficult to
      treat. Animal studies on various seizure models in the hippocampus and the
      entorhinal cortex (EC) suggest that these structures do not a priori produce
      seizures that are difficult to treat. However, seizure-like events in the EC tend
      to progress to a state of status epilepticus-like activity that cannot be
      suppressed by presently marketed AEDs. Loss of gamma-aminobutyric acid
      (GABA)ergic neurotransmission and increased excitatory synaptic coupling seem to
      cooperate for induction of this state. Epilepsy induced alterations in the
      interaction between the EC and the hippocampus may lead to alterations that
      facilitate precipitation of seizures. Because of the recurrent interaction
      between the hippocampus and the EC, these seizures may reach an intensity that is
      no longer controllable by presently available AEDs. Ontogenetic alterations of
      the circuitry between the EC and the hippocampus, seizure-induced stabilization
      of synaptic connections overexpressed during ontogenesis, seizure-induced lesions
      and subsequent rearrangements of internal cell properties, and synaptic
      arrangements and kindling-like alterations of nerve cell and glial behavior may
      all be involved in the generation of a neuronal aggregate whose balance between
      inhibitory and excitatory processes becomes readily disturbed. Strategies for the
      development of AEDs treating such seizures should suppress hyperactivity and
      prevent progression of epileptogenesis. AEDs directed against seizures may be
      effective if they can be given in sufficient concentrations to suppress very
      intense local seizures.

PMID- 7518771
TI  - The three-dimensional structure of human erythrocyte aquaporin CHIP.
AB  - Water-permeable membranes of several plant and mammalian tissues contain specific
      water channel proteins, the 'aquaporins'. The best characterized aquaporin is
      CHIP, a 28 kDa red blood cell channel-forming integral protein. Isolated CHIP and
      Escherichia coli lipids may be assembled into 2-D crystals for structural
      analyses. Here we present (i) a structural characterization of the solubilized
      CHIP oligomers, (ii) projections of CHIP arrays after negative staining or metal
      shadowing, and (iii) the 3-D structure at 1.6 nm resolution. Negatively stained
      CHIP oligomers exhibited a side length of 6.9 nm with four-fold symmetry, and a
      mass of 202 +/- 3 kDa determined by scanning transmission electron microscopy.
      Reconstituted into lipid bilayers, CHIP formed 2-D square lattices with unit cell
      dimensions a = b = 9.6 nm and a p422(1) symmetry. The 3-D map revealed that CHIP
      tetramers contain central stain-filled depressions about the fourfold axis. These
      cavities extend from both sides into the transbilayer domain of the molecule
      leaving only a thin barrier to be penetrated by the water pores. Although CHIP
      monomers behave as independent pores, we propose that their particular structure
      requires tetramerization for stable integration into the bilayer.

PMID- 7518772
TI  - Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a
      binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo.
AB  - Receptor protein-tyrosine phosphatase alpha (RPTP alpha) is a transmembrane
      protein with a short extracellular domain (123 amino acids) and two
      cytoplasmically localized protein-tyrosine phosphatase (PTP) domains. Here we
      report that RPTP alpha is constitutively phosphorylated on tyrosine in NIH 3T3
      mouse fibroblasts. The in vivo tyrosine phosphorylation site was localized to the
      C-terminus of RPTP alpha by phosphopeptide mapping experiments using in vivo and
      in vitro 32P-labeled RPTP alpha. The identity of this site as Tyr789, located
      five residues from the C-terminus, was confirmed by site-directed mutagenesis.
      Transient overexpression of c-Src together with RPTP alpha in human embryonic
      kidney 293 cells increased phosphorylation of Tyr789, suggesting that c-Src may
      phosphorylate RPTP alpha in vivo. RPTP alpha had autodephosphorylation activity
      in vitro. When expressed in 293 cells the level of Tyr789 phosphorylation was
      higher in a non-functional mutant of RPTP alpha than in wild type RPTP alpha,
      indicating that RPTP alpha may have autodephosphorylation activity in vivo as
      well. The sequence on the C-terminal side of Tyr789 (YANF) fits the consensus
      binding site for the SH3-SH2-SH3 adaptor protein GRB2 (YXNX). We show that RPTP
      alpha, but not a mutant of RPTP alpha with a Tyr-->Phe mutation at position 789,
      bound to GRB2 in vitro. In addition, RPTP alpha co-immunoprecipitated with GRB2
      from NIH 3T3 cells, demonstrating that GRB2 bound to RPTP alpha in vivo. The
      guanine nucleotide releasing factor for the Ras GTPase, Son of sevenless (Sos),
      which associates with GRB2 via its SH3 domains, was not detected in RPTP alpha
      immunoprecipitates. Our results suggest a role for RPTP alpha in attenuation of
      GRB2-mediated signaling.

PMID- 7518773
TI  - Mechanism of the down-regulation of cAMP receptor protein by glucose in
      Escherichia coli: role of autoregulation of the crp gene.
AB  - Glucose causes catabolite repression by lowering the intracellular levels of both
      cAMP and cAMP receptor protein (CRP) in Escherichia coli. The molecular mechanism
      underlying the down-regulation of CRP by glucose has been investigated. We show
      that glucose lowers the level of crp mRNA without affecting its stability.
      Replacement of the crp promoter with the bla promoter almost completely abolishes
      the glucose-mediated regulation of crp expression. Only a slight reduction in the
      crp expression by glucose is observed in cya- or crp- strains, suggesting that a
      CRP-cAMP complex is needed for this regulation. We previously showed that
      transcription of the crp gene is regulated both negatively and positively.
      Positive autoregulation of crp is caused by the binding of CRP-cAMP to the CRP
      binding site II located upstream of the crp promoter. Here we show that
      disrupting the CRP binding site II essentially eliminates the down-regulation of
      crp expression by glucose. We conclude that the autoregulatory circuit of the crp
      gene plays a key role in the down-regulation of CRP by glucose.

PMID- 7518774
TI  - TATA-binding protein-associated factor(s) in TFIID function through the initiator
      to direct basal transcription from a TATA-less class II promoter.
AB  - The RNA polymerase II (Pol II) basal transcription factor TFIID is composed of
      the TATA box-binding protein (TBP) and several TBP-associated factors (TAFs). TBP
      is required for Pol II transcription from TATA-containing and TATA-less
      promoters. TATA-less promoters of mRNA-encoding genes often contain an initiator
      element at the transcription start site that is sufficient to direct accurate Pol
      II transcription. Here we address the mechanisms of functional TBP recruitment to
      the TATA-less initiator-dependent promoter of the mouse terminal deoxynucleotidyl
      transferase (TdT) gene. We show that the natural TATA-less TdT initiator region
      is sufficient to promote low levels of specific transcription in vitro and to
      direct the assembly of a stable preinitiation complex. In contrast to what is
      observed for several other promoters lacking a consensus TATA element, the TATA
      binding activity of TBP is not required for the functional recruitment of TFIID
      to the natural TATA-less TdT and beta-polymerase promoters. Moreover, a
      comparison of TBP and highly purified epitope-tagged TFIID reveals that one or
      several TAFs function independently of distal regulatory elements to mediate
      initiator-directed (basal) transcription from the natural TATA-less TdT core
      promoter in crude nuclear extracts. Furthermore, by using a transcription system
      reconstituted with purified components, we present the first evidence for a basal
      transcription function of TAFs through the TdT initiator element. Altogether, our
      results suggest an alternative pathway for TFIID recruitment to initiator
      dependent TATA-less class II promoters in which TAF(s) recruit TBP by interacting
      either directly or indirectly with the initiator region.

PMID- 7518776
TI  - Characterization of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced brain serotonin
      metabolism in the rat.
AB  - It has previously been shown that a lethal dose of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) increases the brain concentrations of serotonin precursor,
      tryptophan, and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in TCDD
      susceptible Long-Evans but not in TCDD-resistant Han/Wistar rats. In the present
      study, TCDD (50 micrograms/kg; LD100 for Long-Evans and nonlethal for Han/Wistar
      rats) enhanced de novo biosynthesis of serotonin in the brain of Long-Evans but
      not Han/Wistar or food-restricted Long-Evans rats 10 days after exposure.
      Furthermore, TCDD increased the plasma level of free tryptophan in Long-Evans
      rats alone, which may be causally related to the observed effects of TCDD on
      brain tryptophan levels. Administration of hemin modified the time course of TCDD
      induced anorexia although 10 day cumulative food consumption was not altered.
      Hemin tended to attenuate TCDD-elicited increases in brain serotonin turnover,
      whereas a beta-adrenergic blocker, propranolol, did not. In the majority of Long
      Evans rats, TCDD inhibited the main tryptophan degrading enzyme in the liver,
      tryptophan pyrrolase, but the rest exhibited augmented activities; these effects
      were not altered by hemin. TCDD increased the plasma levels of nonesterified
      fatty acids in Long-Evans (five-fold) but not in Han/Wistar rats. A slight
      elevation (two-fold) was also seen in food-restricted Long-Evans rats. It is
      concluded that TCDD selectively promotes brain serotonin turnover in Long-Evans
      rats and this acceleration is related to increased plasma levels of free
      tryptophan. The inhibition of tryptophan catabolism in the liver and elevation of
      plasma nonesterified fatty acids may contribute to these changes.

PMID- 7518775
TI  - Modulation of allergen-induced nasal symptoms and mediator release by treatment
      with N-acetyl-aspartyl-glutamate (ZY15106).
AB  - The aim of this study was to evaluate the effects of the new anti-allergic drug,
      N-acetyl-aspartyl-glutamate (ZY15106), on allergen-induced nasal symptoms and
      mediator release. Fifteen outpatients suffering from seasonal allergic rhinitis
      due to grass pollen were included in the study. A nasal antigen challenge
      followed by evaluation of symptoms was performed in basal conditions. Ten of the
      15 patients underwent sequential nasal lavages in order to evaluate allergen
      induced mediator release. The study was performed in winter, when the patients
      were symptom free, and was a randomized single-blind crossover trial of a 6%
      solution of ZY15106 (daily dosage: 48 mg) versus placebo (lactose). The drug and
      the placebo were administered intranasally q.i.d. for 1 week, with a 2-week
      interval between the two treatments. Treatment with ZY15106, but not with
      placebo, caused a significant reduction in nasal obstruction in the first 30 min
      after challenge and at 60 min and itching in the first 10 min after challenge,
      but did not reduce sneezing and rhinorrhoea. Moreover, ZY15106 significantly
      reduced the histamine release in 5 min postchallenge lavage (4.5 ng.ml-1 after
      placebo administration vs 2.5 ng.ml-1, after treatment with ZY15106). A reduction
      in immunoreactive LTC4 release in the 5 and 10 min post-challenge lavages was
      observed after ZY15106 administration (placebo vs active treatment: at 5 min 2.9
      ng.ml-1 vs 1.4 ng.ml-1; at 10 min: 2.25 ng.ml-1 vs 0.9 ng.ml-1).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7518778
TI  - [Biological monitoring of lead in the study of urban pollution due to automobile
      traffic].
AB  - The Authors have reviewed the most important literature available on the
      determination of blood lead level in non-occupationally exposed subjects,
      children and groups exposed to vehicular traffic (i.e. policemen, bus drivers,
      etc.). They have also collected data concerning lead concentration in air
      (mcg/m3) and in gasoline (g/l). The results show that the gradual decrease of
      gasoline lead concentrations gives a consistent decrease of blood lead level in
      the general population. In Italy, in the nonoccupationally exposed subjects, the
      mean blood lead level in 1974 was 32 mcg/dl and in 1991 was 8,4 mcg/dl. The mean
      value in children is presently about 8,3 mcg/dl. The values in workers exposed to
      vehicular traffic are higher than those found in non-exposed population.

PMID- 7518779
TI  - G- and GM-CSF in oncology and oncological haematology.
AB  - Administration of G- and GM-CSF increases the neutrophil counts in a number of
      clinical situations. GM-CSF shows the additional effect of increasing the number
      of monocytes and eosinophil granulocytes. Both G- and GM-CSF affect of neutrophil
      functions, in the case of GM-CSF there are some potentially negative effects on
      neutrophil migration and adhesiveness. The clinical relevance of the various
      effects on mature haematopoietic cells is not fully understood. Clinical data
      with G-CSF treatment indicate that increased levels of neutrophil granulocytes
      following cytotoxic chemotherapy may translate into clinical benefit such as a
      decreased rate of neutropenic infection and an increased cytotoxic chemotherapy
      dose even though the data are conflicting and the risk of "laboratory cosmetics"
      is apparent. Regarding treatment with GM-CSF following chemotherapy, the clinical
      benefit is unclear. The clinical benefit of GM-CSF-induced monocytes and
      eosinophils is unknown. G- and GM-CSF accelerates neutrophil recovery following
      autologous or allogeneic BMT. The influence on neutropenic infections is,
      however, less impressive. Pretreatment with G- or GM-CSF increases the yield of
      peripheral stem cell harvest, thereby reducing the number of leukaphereses
      needed. Transplantation of G- and GM-CSF primed autologous peripheral stem cells
      tends to reduce the period of post-transplant cytopenia, particularly
      thrombocytopenia, in comparison with traditional ABMT. In patients with MDS, G-
      and GM-CSF appear to increase the number of neutrophil granulocytes and there is
      some evidence that patients with severe infectious problems will benefit from
      this treatment. However, little influence was seen on the main clinical problems
      with these patients, which are anaemia and thrombocytopenia. In conclusion, G-
      and GM-CSF are two different proteins with different properties in vivo and in
      vitro. GM-CSF has, compared with G-CSF, more complex pharmacological effects and
      a more trouble-some side-effect profile. Early clinical development indicates
      that both compounds have a substantial influence on the levels of certain blood
      cells. Whether the increases in different blood cells translate into long-term
      clinical benefit for greater patient groups is the focus of ongoing research. The
      effects of G- and GM-CSF may be potentiated by other cytokines, an area which is
      presently being explored.

PMID- 7518780
TI  - Insulin increases guanosine-3',5'-cyclic monophosphate in human platelets. A
      mechanism involved in the insulin anti-aggregating effect.
AB  - To investigate whether insulin reduces platelet aggregability through a
      modulation of the guanosine-3',5'-cyclic monophosphate (cGMP) concentrations, we
      determined by a radioimmunoassay the cGMP values in the platelet-rich plasma
      (PRP) obtained from 17 healthy volunteers and incubated for 3 min with different
      concentrations of human recombinant insulin (0, 240, 480, 720, 960, and 1,920
      pM). Insulin induced a dose-dependent cGMP increase, from 18.5 +/- 3.3 to 42.0 +/
      6.4 pmol/10(9) platelets (P = 0.0001). This increase was completely blunted when
      PRP was preincubated for 20 min with the tyrosine kinase inhibitor genistein (10
      microM) or with the guanylate cyclase inhibitor methylene blue (10 microM), but
      the increase remained highly significant (P = 0.003 and 0.009) when PRP was
      preincubated for 20 min with the phosphodiesterase inhibitor 3-isobutyl-1-methyl
      xanthine (IBMX, 500 microM) or with the nitric oxide synthase inhibitor NG-mono
      methyl-L-arginine (L-NMMA, 30 microM). Finally, the insulin-induced decrease of
      platelet aggregability to collagen and ADP was completely blunted when PRP was
      preincubated with 10 microM of the guanylate cyclase inhibitor methylene blue.
      This study demonstrates that the platelet anti-aggregatory effect exerted by
      insulin is attributable to the insulin-induced increase of cGMP that is due to a
      direct receptor-mediated platelet guanylate cyclase activation.

PMID- 7518777
TI  - The effects of toluene diisocyanate and of capsaicin on human bronchial smooth
      muscle in vitro.
AB  - Toluene diisocyanate contracts guinea-pig bronchial smooth muscle through a
      mechanism involving capsaicin-sensitive sensory nerves. In the present study, we
      investigated the effects of toluene diisocyanate, capsaicin and tachykinins on
      isolated human bronchi. In 44 rings, toluene diisocyanate (0.3 mM) produced a
      relaxation which averaged 16.9 +/- 1.1%, in ten rings it produced a shortening
      that was 15.1 +/- 3.3% and in ten preparations it gave no response. A second
      administration of toluene diisocyanate (0.3 mM) always produced a relaxation (n =
      13, 18.1 +/- 3.9%). Capsaicin (0.03 mM) produced shortening in 15 (35 +/- 6.6%)
      and relaxation in 11 preparations (41 +/- 6.8%), whereas a second administration
      caused shortening in nine (25.1 +/- 6.1%) and relaxation in 16 rings (36.4 +/-
      4.9%). When toluene diisocyanate was given after two consecutive capsaicin
      administrations, we observed shortening in two rings (10.0 +/- 3.6%), relaxation
      in ten rings (15.9 +/- 3.6%), and no response in four preparations. To test the
      role of NK1 and NK2 receptors in these conflicting responses, we performed
      concentration-response curves to different tachykinins. Substance P, neurokinin A
      and neurokinin A-(4-10), a specific NK2 receptor agonist, gave a concentration
      dependent shortening, with neurokinin A being the most effective and neurokinin A
      (4-10) the least. The specific NK1 receptor agonist, [Sar9, Met(O2)11]substance
      P, produced both shortening and relaxation. We conclude that toluene diisocyanate
      and capsaicin may produce both shortening and relaxation in isolated human
      bronchi through NK1 receptors.

PMID- 7518783
TI  - FK506 enhances fibrogenesis in in vitro and in vivo models of liver fibrosis in
      rats.
AB  - BACKGROUND/AIMS: The immunosuppressant FK506 is undergoing clinical trials in
      transplantation and autoimmune diseases. FK506 modulates several cytokines and
      exerts hepatoprotection in acute models. This study was initiated to determine
      whether FK506 would be beneficial as an antifibrogenic agent. METHODS: Fibrosis
      was induced by carbon tetrachloride administration to rats. Half of those animals
      were treated with FK506. The rats were killed after 8 weeks of carbon
      tetrachloride treatment. The livers were evaluated by histology, Northern
      hybridizations, and collagen quantitation. Additionally, rat fibroblasts were
      incubated with and without FK506 and used for Northern hybridization analysis.
      RESULTS: Surprisingly, FK506 exacerbated hepatic inflammation and fibrosis.
      Increased hepatic collagen and higher messenger RNA levels of transforming growth
      factor beta 1 and collagens I, III, and IV were found in the FK506-treated group.
      Rat fibroblasts treated with FK506 expressed higher levels of collagens I and
      III, fibronectin, macrophage-colony stimulating factor, tissue inhibitor of
      metalloprotease, and transforming growth factor beta 1 messenger RNAs.
      CONCLUSIONS: These findings suggest that FK506 increases the expression of
      extracellular matrix genes and enhances fibrosis in the rat model. While further
      studies are needed to elucidate these profibrogenic mechanisms, caution is
      indicated for the unrestricted use of FK506 in patients subject to recurrent
      fibrogenic stimulation.

PMID- 7518782
TI  - Butyrate is a potent inhibitor of urokinase secretion by normal colonic
      epithelium in vitro.
AB  - BACKGROUND/AIMS: Because the neutral protease urokinase is important in control
      of cell adhesion and migration, the effects of the physiologically relevant
      fermentation product butyrate on urokinase secretion by colonic epithelium were
      examined. METHODS: Secreted and cell-associated levels of urokinase and
      plasminogen activator inhibitor 1 were measured in colonic crypt cells within 24
      hours of isolation from macroscopically normal mucosa of normal or cancer-bearing
      colons. RESULTS: Butyrate caused a concentration-dependent inhibition of both
      secreted (56% +/- 4% inhibition after 24-hour exposure to 1 mmol/L butyrate; n =
      20; mean +/- SEM; P < 0.001) and cell-associated urokinase content (35% +/- 6%; P
      = 0.003). Acetate and propionate had minimal effects. Butyrate also stimulated
      plasminogen activator inhibitor 1 secretion by 25% +/- 7% (P = 0.013). Net
      urokinase activities were suppressed in supernates and cell homogenates by
      butyrate. Levels of transcripts for urokinase and the inhibitor changed with
      butyrate exposure in parallel to the levels of secretion of the respective
      proteins. Cells from the cancer group showed significantly reduced inhibitor
      secretion and abnormal responses to butyrate (greater inhibition of urokinase
      secretion and no stimulation of inhibitor secretion), probably reflecting the
      diffuse disturbance of colonic epithelial biology associated with colorectal
      cancer. CONCLUSIONS: Butyrate has dual effects in markedly reducing colonic
      epithelial urokinase activity, and these may have important implications to
      understanding colonic epithelial physiology and the pathogenesis and treatment of
      colonic diseases.

PMID- 7518784
TI  - Reciprocal regulation of alpha-fetoprotein and albumin gene expression by
      butyrate in human hepatoma cells.
AB  - BACKGROUND/AIMS: Butyrate, a product of colonic bacterial flora, functions as an
      antiproliferative agent and induces cell differentiation in a variety of cell
      types. In the present study, the effects of butyrate on cell growth and
      expression of alpha-fetoprotein (AFP) and albumin genes in HuH-7 human hepatoma
      cells were investigated. METHODS: The HuH-7 cells were treated with sodium
      butyrate (0-1 mmol/L), and numbers of viable cells were counted at 24, 48, and 72
      hours after treatment. To elucidate the effects of sodium butyrate on AFP and
      albumin gene expression, Northern blotting and transient chloramphenicol
      acetyltransferase plasmid transfection experiments were performed. RESULTS: Cell
      growth was dose dependently inhibited by sodium butyrate. By Northern blot
      analysis, the level of AFP messenger RNA was reduced by treatment with sodium
      butyrate, whereas the level of albumin messenger RNA was elevated by this
      treatment. In transient chloramphenicol acetyltransferase plasmid transfection
      experiments, sodium butyrate repressed the AFP promoter activity but did not
      change the AFP enhancer or silencer activities. In contrast, the albumin promoter
      activity was stimulated by sodium butyrate. CONCLUSIONS: These results suggest
      that butyrate leads to the reciprocal differentiating regulation of AFP and
      albumin gene expression at the transcriptional level in human hepatoma cells.

PMID- 7518786
TI  - Naturally occurring PIA/PIB hybrids of Neisseria gonorrhoeae.
AB  - The major outer membrane protein of Neisseria gonorrhoeae, Por, functions as a
      porin and is thought to occur as one gene with two alleles. The immunologically
      distinct epitopes of the two subclasses, IA and IB, have allowed the development
      of serotyping schemes. Clinical isolates of N. gonorrhoeae are believed to
      express only a single type of Por, either IA or IB. We have encountered two
      clusters of isolates that react with antibodies to both IA and IB Por. Isolates
      within the clusters are indistinguishable by the phenotypic characteristics
      tested. In addition, the amplification of the por gene in representative isolates
      showed that the por gene of the hybrids gave similar restriction digest patterns
      within but not between the clusters.

PMID- 7518785
TI  - Expression of complement-regulatory proteins in normal and UW-preserved human
      liver.
AB  - BACKGROUND/AIMS: Somatic cells are protected against complement-mediated injury
      by specialized membrane proteins, known as complement-regulatory proteins (CRP).
      The knowledge of the pattern of CRP expression in the liver is important to
      evaluate the role of complement-mediated injury in graft rejection. METHODS: We
      determined the distribution of four main CRP: membrane cofactor protein (MCP),
      decay accelerating factor (DAF), protectin, and complement receptor 1 (CR1) in 30
      histologically normal livers, 13 samples from University of Wisconsin cold
      storage solution (UW)-preserved tissue and 17 postoperative biopsies of UW
      preserved allografts. RESULTS: In normal liver, hepatocytes expressed only MCP.
      Bile duct cells were reactive for MCP and protectin. Sinusoidal endothelial cells
      expressed MCP and protectin but displayed no or faint expression of DAF.
      Endothelial cells of portal vessels and centrilobular veins expressed high levels
      of DAF, MCP, and protectin. No expression of CR1 was observed. No change in CRP
      expression was usually detected after UW preservation, except for protectin,
      induced on hepatocytes in 9 samples of UW-preserved liver tissue and in 9
      allografts. CONCLUSIONS: Hepatocytes and sinusoidal endothelial cells, which have
      a defective expression of CRP, might be at risk for complement-mediated injury.
      However, this risk is not aggravated after UW preservation.

PMID- 7518781
TI  - Long-acting somatostatin analogue therapy and protein metabolism in patients with
      jejunostomies.
AB  - BACKGROUND/AIMS: Previous studies have shown that secretory losses in patients
      with end jejunostomy syndrome (EJS) on home parenteral nutrition (HPN) can be
      suppressed by the somatostatin analogue, octreotide, thus facilitating fluid
      balance. However, the hormone also has antianabolic actions that may interfere
      with the use of infused amino acids. METHODS: Amino acid metabolism, pancreatic
      enzyme synthesis and secretion, and mucosal protein turnover were measured by
      primed/continuous intravenous infusion of [1-14C] leucine tracer, duodenal
      aspiration, and endoscopic mucosal biopsy techniques during hormonal stimulation
      with pentagastrin and cholecystokinin 8. RESULTS: In comparison with normal
      healthy controls, baseline measurements of amino acid metabolism were normal in
      patients with EJS/HPN, but pancreatic enzyme synthesis and secretion were
      elevated. Octreotide therapy improved fluid balance but suppressed gut hormone
      (insulin, gastrin, glucagon, peptide YY) levels in blood and the uptake of amino
      acids into pancreatic enzyme and mucosal proteins, increasing oxidative losses.
      CONCLUSIONS: Octreotide improves fluid balance in patients who have undergone
      jejunostomy but reduces the use of amino acids for splanchnic protein synthesis.
      This may interfere with the physiological process of adaptation to intestinal
      resection.

PMID- 7518788
TI  - Structure and organization of a stable extrachromosomal element in human cells.
AB  - We have determined the structure and organization of a 630-kb extrachromosomal
      element (amplisome) containing the dihydrofolate reductase-encoding gene (DHFR)
      in a methotrexate (MTX)-resistant human cell line, HeLa-Bu25-10B3. The size and
      copy number of amplisomes have previously been found to remain remarkably stable
      with or without selection. Both linear and open circular 630-kb amplisomes are
      present in these cells. We have been able to isolate the linear amplisomes after
      pulsed-field gel electrophoresis (PFGE), and transfect the amplisomes into MTX
      sensitive recipient cells by electroporation, thus demonstrating that DNA as
      large as 630 kb can be transfected into mammalian cells. The NotI restriction
      site immediately upstream from DHFR on the circular amplisome is devoid of
      methylation, suggesting that it is transcriptionally active. Restriction mapping
      by PFGE reveals that there is only one copy of DHFR per amplisome and no
      repetitive structure is observed. The small size of the amplisomes, their
      stability and our ability to transfect large DNA molecules provide the necessary
      ingredients for the development of mammalian cloning vectors for large DNA
      fragments.

PMID- 7518787
TI  - Psychotherapy of the otolaryngology patient.
AB  - Psychotherapy is an essential skill in the treatment of the medically ill
      patient. It represents to a significant extent the manner in which we understand
      and intervene in the patient's efforts to cope with overwhelming loss and grief.
      Psychotherapy of the Otolaryngology patient is especially challenging because of
      the substantial impediments to communication in this population. This paper will
      review some of the special issues that apply to many medically or surgically ill
      individuals but which are almost universal to the Otolaryngology patients. In
      particular the special topics of "Body Image" including disfigurement and
      cosmetic surgery, and "The Role of Verbalization" will be discussed.
      Consideration is also given to the special topic of countertransference which is
      also encountered in psychotherapy in reaction to these patients.

PMID- 7518789
TI  - Identification of homeobox genes expressed in human haemopoietic progenitor
      cells.
AB  - Homeodomain (HD)-containing proteins have been shown to regulate cellular
      commitment and differentiation in fungal, invertebrate and vertebrate systems.
      Bone marrow cells synthesizing the CD34 antigen are a complex mix of early, stem
      and progenitor cells at various stages of commitment to the many haemopoietic
      lineages. Here, we report the cloning and sequencing of 31 homeobox (HB)
      sequences, identified using degenerate oligodeoxyribonucleotide primers, in a
      polymerase chain reaction with cDNA derived from a purified CD34+ population of
      human haemopoietic cells. Of these sequences, 16 correspond to previously
      identified genes, and 13 are located within the HOX A, B and C clusters. Ten of
      the clones most likely represent human homologues of genes identified previously
      in other species. Five of the clones reported here represent novel HD sequences.
      The identification of five new genes using a subclass-specific 5' primer,
      designed from the engrailed and Xanf1 sequences, suggests that there still remain
      several uncharacterized HB genes in the human genome. Haemopoietic cells purified
      on the basis of CD34 antigen synthesis are a rich source of regulatory genes
      consistent with their ability to differentiate into diverse haemopoietic cell
      types.

PMID- 7518790
TI  - The interferon-inducible GBP1 gene: structure and mapping to human chromosome 1.
AB  - We have isolated DNA clones containing the interferon (IFN)-inducible guanylate
      binding protein-1-encoding gene (GBP1) from a human genomic library. Two
      overlapping phage clones contained the entire GBP1 gene. The 2880 bp
      corresponding to the GBP1 cDNA were subdivided into eleven exons which were
      interrupted by a total of 9500 bp of intron DNA. All exon/intron junctions
      contained consensus splice donor and acceptor sequences. Using hybrid rodent cell
      lines containing human chromosomes, GBP1 was mapped to human chromosome 1. In
      addition to GBP1, we detected and partially characterized a novel gene, GBP3,
      with a structure related to GBP1 and a high degree of sequence homology to both
      GBP1 and GBP2. Our data suggest that the GBP family of genes contains members
      other than the previously characterized GBP1 and GBP2.

PMID- 7518792
TI  - Productive re-arrangement at both alleles of the T-cell receptor beta-chain locus
      in CD4 T-cell clones specific for influenza haemagglutinin.
AB  - T-cell receptor (TcR) beta-chain usage, and VDJ junctional region sequences
      thereof in a panel of CD4+ T-cell clones Ad-, or Ak- or Ek-restricted for major
      antigenic sites of influenza haemagglutinin (H3 subtype), were investigated.
      Direct sequencing of cDNA, obtained by polymerase chain reaction, revealed that
      the majority of T-cell clones contained both productive and non-productive
      rearranged transcripts. Moreover, T-cell clones specific for p206-227 (Ad) or
      p245-265 (AK) contained double-productive re-arranged transcripts (V beta 6 J
      beta 2.6, V beta 4, J beta 1.2) and (V beta 6 J beta 1.3, V beta 8.2, J beta 1.5)
      respectively. However, FACS analysis with V beta-specific monoclonal antibodies
      established that, for each of these T-cell clones, only a single beta-chain was
      expressed at the cell surface, thereby indicating post-transcriptional editing.

PMID- 7518791
TI  - Modulation of the immune response with T-cell epitopes: the ultimate goal for
      specific immunotherapy of autoimmune disease.

PMID- 7518794
TI  - Adhesion and penetration properties of human lymphocytes acting on allogeneic
      vascular endothelial cells.
AB  - Lymphocyte infiltration through vascular endothelium is one important step in the
      course of graft rejection. To investigate this process more exactly we
      established a monolayer invasion assay which enabled us to discriminate between
      adherent and penetrated cells. Detailed studies of adhesion and penetration
      kinetics of peripheral blood lymphocytes (PBL) acting on allogeneic human
      umbilical vein endothelial cells (HUVEC) were carried out by combined phase
      contrast and reflection interference contrast microscopy. Between 30 and 35% of
      all PBL attached to HUVEC after 4 hr. Out of these less than 10% penetrated. When
      HUVEC were prestimulated for 2 hr by interferon (IFN)-alpha,-beta,-gamma or
      interleukin (IL)-1, PBL adhesion in the early phase of cellular attachment to
      endothelial cells was accelerated. Overall adhesion however did not increase.
      Long-term pretreatment of HUVEC for 72 hr with IFN-gamma or IL-1 also modified
      PBL-HUVEC interactions. However, a 72-hr pretreatment with IFN-alpha or -beta did
      not influence lymphocyte binding behaviour. PBL penetration was not only
      accelerated but also enhanced by IFN-alpha,-beta,-gamma, irrespective of whether
      HUVEC were prestimulated for 2 hr or PBL and cytokines were added simultaneously
      to HUVEC. On the other hand IL-1 was not able to enhance the amount of penetrated
      cells but only accelerated the infiltration process. Up-regulation or de novo
      expression of the adhesion molecules ICAM-1 (intercellular adhesion molecule),
      ELAM-1 (endothelial leucocyte adhesion molecule) and VCAM-1 (vascular cell
      adhesion molecule) did not parallel PBL binding kinetics. Therefore an ICAM-,
      ELAM- and VCAM-independent modulation in the early phase of lymphocyte attachment
      to endothelium seems likely. The lymphocyte cytoskeleton may have a role in this
      process.

PMID- 7518795
TI  - Identification of hybridomas derived from mouse CD5+ B lymphocytes by fluorescent
      staining for cytoplasmic CD5 expression.
AB  - The production of hybridomas derived from CD5+ B lymphocytes is important for
      studying the immunoglobulin gene repertoire and antibody specificity of this B
      lymphocyte subpopulation. However, hybridomas derived from these lymphocytes
      invariably lose surface membrane expression of CD5 following hybridization. This
      impedes the unequivocal assignment of the generated hybridomas to the CD5+ B
      lymphocyte subpopulation from unsorted, or partially sorted, cells. Recent
      studies have shown that mRNA transcripts of the CD5 gene and the protein product
      can be detected in the cytoplasm of some mouse hybridomas, indicating that
      although surface expression has been lost, they may have been generated from CD5+
      B lymphocytes. These studies, however, have been unable to discount completely
      the possibility that aberrant cytoplasmic expression of the CD5 gene occurred as
      a direct consequence of the hybridization process. To confirm that cytoplasmic
      CD5 expression in the hybridomas is in fact directly related to the B-lymphocyte
      origin we have generated hybridomas from FACS-sorted CD5+ and CD5- murine splenic
      B lymphocytes, and determined their surface and cytoplasmic CD5 expression by
      fluorescence-activated cell sorting. Our findings reveal that all hybridomas
      derived from CD5+ B lymphocytes (nine hybridomas) were negative for surface but
      positive for cytoplasmic CD5 expression, whereas all hybridomas derived from CD5-
      B lymphocytes (nine hybridomas) were negative for both surface and cytoplasmic
      CD5 expression. This finding shows that staining for cytoplasmic CD5 expression
      provides an accurate method of determining the cellular origin of murine B
      lymphocyte hybridomas.

PMID- 7518796
TI  - Discrimination between two subsets of porcine CD8+ cytolytic T lymphocytes by the
      expression of CD5 antigen.
AB  - Previous work has revealed striking differences in the peripheral T-lymphocyte
      compartments of swine compared to other species. The key difference is the
      existence of four T-lymphocyte subpopulations defined by their CD4/CD8
      expression. Besides this difference in the CD4/CD8 antigen expression, we report
      here another unusual antigen distribution on porcine extrathymic T lymphocytes:
      the expression of the 63,000 MW CD5 antigen. In porcine thymus the CD5 antigen
      shows a biphasic antigen density, whereas the majority of thymocytes are
      characterized by an intermediate CD5 expression. In the extrathymic T-lymphocyte
      compartment, CD5 also shows a heterogeneous antigen distribution as defined by
      three subsets: CD5high, CD5dim and CD5- T lymphocytes. Analyses of the CD5
      expression on the four CD4/CD8-defined peripheral T-cell subpopulations revealed
      that all CD4+ T lymphocytes, CD4+ CD8+ as well as CD4+ CD8- T lymphocytes,
      belonged to the subset with high CD5 antigen density. The CD4- CD8-
      subpopulation, containing in the majority T-cell receptor (TcR) gamma delta T
      lymphocytes, was characterized by dim CD5 expression. The most notable difference
      was the division of the CD4- CD8+ cytolytic T-lymphocyte subpopulation into two
      CD5-defined subsets: CD4- CD5- CD8+ lymphocytes with spontaneous cytolytic
      activity against tumour cells, and CD4- CD5+ CD8+ T lymphocytes with major
      histocompatibility complex (MHC)-restricted cytolytic function. Thus, the porcine
      CD5 antigen is an important marker to discriminate between CD5- CD8+ natural
      killer (NK) cells and CD5+ CD8+ progenitors of MHC-restricted cytolytic T
      lymphocytes.

PMID- 7518793
TI  - The costimulatory molecule B7 is expressed in the medullary region of the murine
      thymus.
AB  - Several laboratories, including our own, have previously shown that the B7
      antigen, a glycoprotein expressed on activated B cells, macrophages and dendritic
      cells, can provide a potent costimulatory signal for peripheral murine T
      lymphocytes. In the present report we have analysed the expression and function
      of B7 in the murine thymus. The expression of B7 was demonstrated
      histochemically. B7-expressing cells were present in the thymic medulla but
      virtually absent from the cortex. Further analysis by immunofluorescence and flow
      fluorocytometry revealed that the B7-positive cells also expressed major
      histocompatibility complex (MHC) class II molecules. Both epithelial and
      dendritic cells expressed the B7 antigen. Finally, although we have demonstrated
      expression of mB7 in the murine thymus, we have been unable to detect a function
      for this antigen in this organ. The implications of these findings are discussed.

PMID- 7518797
TI  - Human eosinophils as antigen-presenting cells: relative efficiency for
      superantigen- and antigen-induced CD4+ T-cell proliferation.
AB  - Human eosinophils become hypodense and express class II major histocompatibility
      (MHC) molecules when activated by granulocyte-macrophage colony-stimulating
      factor (GM-CSF) in vitro or in vivo in pathological conditions such as allergic
      disorders. In this study, we examined the capacity of class II MHC-expressing
      eosinophils to serve as antigen-presenting cells (APC) for resting and activated
      CD4+ T cells. Eosinophils were isolated from healthy donors and incubated in
      conditioned medium (CM) containing GM-CSF for 2-4 days, after which 15-92% of the
      cells expressed class II MHC (HLA-DR). Preincubated eosinophils induced resting T
      cells to proliferate in response to the staphylococcal superantigens,
      Staphylococcus enterotoxins A, B and E. Furthermore, superantigen-induced T-cell
      proliferation correlated with the proportion of eosinophils expressing class II
      MHC molecules. When eosinophils and macrophages were compared for their ability
      to act as accessory cells for superantigen-induced T-cell proliferation,
      macrophages were more efficient than eosinophils. Eosinophils were not effective
      APC for microbial antigens (Ag), which required processing. Proliferative
      responses to purified protein derivative, tetanus toxoid, or Brugia malayi
      antigen were observed in only three of nine studies. The three positive studies
      included activated CD4+ T cells, whereas no responses were observed with resting
      CD4+ T cells. Macrophages and mononuclear cells were effective APC for these Ag
      for both resting and activated CD4+ T cells. These data indicate that although
      class II MHC-expressing eosinophils can serve as APC, they are relatively
      inefficient for the activation of CD4+ T cells by Ag, which require processing.

PMID- 7518799
TI  - Presence of a dysfunctional form of CD59 on a CD59+ subclone of the U937 cell
      line.
AB  - U937 cells are known to be relatively sensitive to C-mediated killing and have
      been reported to show variable expression of CD59. We have obtained stable CD59+
      and CD59- sublines of the U937 cell line. Expression of other C-regulatory
      proteins, decay-accelerating factor (DAF), MCP and CR1, was similar on both cell
      lines. Although the sublines were morphologically similar and expressed similar
      amounts of most surface antigens, qualitative difference in expression of CD13
      and CD64 and a quantitative difference in CD15 expression was observed.
      Sensitivity to C-mediated killing of the cell lines was measured using classical
      pathway activation. Both cell lines appeared to be equally sensitive to C
      mediated killing. Monoclonal antibodies against CD59, which neutralize CD59 and
      enhance killing of most cell lines (including K562, HL60 and Molt4), did not
      enhance the killing of the CD59- cells but, surprisingly, also did not enhance
      killing of the CD59+ U937 subline. CD59 was expressed on the U937 subline at
      similar levels to that on HL60 and K562 cells, was glycosylphosphatidylinositol
      (GPI) anchored and could be immunoprecipitated from cell extracts. However,
      unlike these other cell lines, U937 cell extracts were negative in a Western blot
      using a variety of anti-CD59 antibodies even when ultrasensitive detection
      methods were used. These results indicate that the CD59+ U937 cell expresses a
      form of CD59 which is dysfunctional and structurally abnormal.

PMID- 7518798
TI  - Polyclonal B-cell activation in cats infected with feline immunodeficiency virus.
AB  - The specificity of the antibody response following natural or experimental
      infection of domestic cats with feline immunodeficiency virus (FIV) was examined.
      The antibody response to a range of non-viral antigens, including trinitrophenol
      (TNP), ovalbumin, beta-galactosidase, deoxyribonucleic acid (DNA) and keyhole
      limpet haemocyanin (KLH), was measured in 220 cats naturally infected with FIV.
      Infected cats had higher antibody levels to these antigens, in particular TNP,
      KLH and beta-galactosidase, than non-infected control cats. Competition binding
      studies demonstrated that this response was not due to the presence of cross
      reacting epitopes on recombinant FIV p17 or p24 antigens, suggesting that the B
      cell activation associated with infection was polyclonal rather than entirely
      virus specific. Studies on cats experimentally infected with FIV revealed a
      similar pattern, with infected cats developing an antibody response to
      heterologous non-viral antigens at 6-8 weeks post-infection. There were two
      discernible peaks of antibody activity, the first occurring 10-20 weeks post
      infection and the second peak 40-60 weeks post-infection. The antibody response
      to KLH, DNA and beta-galactosidase remained elevated throughout the 90-week study
      period, whereas the antibody levels to the other antigens declined to levels
      approaching those observed in normal cats.

PMID- 7518800
TI  - Expression and function of multiple regulators of complement activation in
      autoimmune thyroid disease.
AB  - Membrane attack complexes of complement occur around thyroid follicles in Graves'
      disease and Hashimoto's thyroiditis. The lytic potential of such complexes is
      controlled by membrane-bound and fluid phase regulators and we have investigated
      the role of these in autoimmune thyroid disease. By immunohistochemical staining,
      clusterin and S-protein were found in all nine thyroid specimens from patients
      with Graves' disease and S-protein was found in one of two Hashimoto glands.
      CD46, CD55 and CD59 were found on thyroid cells in all specimens. CD46 and CD55
      expression occurred on thyroid cells cultured in vitro and was increased
      significantly by culture with interleukin-1 (IL-1) and interferon-gamma (IFN
      gamma), which are known to be released by the lymphocytic infiltrate in these
      conditions. Blocking CD55 had a weak and inconsistent effect on complement
      mediated thyroid cell killing in vitro but, in four of five experiments, blocking
      CD46 enhanced killing. However, the effect of blocking CD59 was greater in all
      cases than blocking CD46 or CD55. Expression of these fluid phase and membrane
      bound proteins may be important in determining the severity of thyroid damage
      produced by complement fixation in Graves' disease and Hashimoto's thyroiditis.

PMID- 7518801
TI  - Bovine conglutinin binds to an oligosaccharide determinant presented by iC3b, but
      not by C3, C3b or C3c.
AB  - Bovine conglutinin is a serum lectin that agglutinates erythrocytes preincubated
      with antibodies and complement. This agglutination occurs through the binding of
      conglutinin to iC3b, a fragment of the complement component C3. It was reported
      that conglutinin binds fluid-phase C3b and C3c as well as iC3b. We re
      investigated the reactivity of conglutinin towards fluid-phase C3 degradation
      products. ELISA wells were coated with conglutinin and reacted with C3 split
      products generated in normal human serum, in factor I-deficient serum, or in
      factor I-depleted serum. Conglutinin-bound C3 fragments were detected with anti
      C3c and anti-C3d antibodies. An increased signal was observed during the
      activation of complement in normal human serum with the peak response after 1-2
      hr, following which the signal decreased, reaching background level after 72 hr.
      The oligosaccharides on C3c, generated in serum, are thus not recognized by
      conglutinin. No signal was observed when factor I-deficient serum or factor I
      depleted serum was used instead of normal serum. Reconstitution with purified
      factor I re-established the normal pattern. Examination of the conglutinin-bound
      C3 molecules by SDS-PAGE and Western blotting with anti-C3c and anti-C3d
      antibodies revealed bands characteristic for iC3b, and no bands corresponding to
      C3b or C3c. Reduction of the disulphide bonds prior to the incubation of the
      activated serum with the conglutinin-coated wells revealed a band of 63,000 MW,
      characteristic of the N-terminal fragment of the alpha-chain of iC3b. We also
      investigated the binding to the solid-phase conglutinin of purified C3 and
      degradation products generated with enzymes. In this case, C3 as well as C3b and
      C3c were bound, suggesting conformational changes in C3 during purification. In
      conclusion, when C3 conversion takes place at near physiological conditions,
      conglutinin interacts specifically with the oligosaccharide on the alpha-chain of
      iC3b.

PMID- 7518803
TI  - Evidence for a trans-acting activator function regulating the expression of the
      human CD5 antigen.
AB  - Interspecies somatic cell hybrids were generated by fusing the mouse T-lymphoma
      cell line, BW5147, with normal human T lymphocytes at different stages of
      differentiation. Thymocytes, activated peripheral T lymphocytes, or an activated
      T-cell clone were used as human partners, respectively, in three independent
      fusions. Irrespective of the human cell partner used for fusion, a certain number
      of hybrids lost CD5 surface expression over a period of time in culture. Analysis
      at the phenotype and genetic level showed that lack of CD5 expression was due
      neither to segregation of human autosome 11, on which the CD5 gene has been
      mapped, nor to deletion of the CD5 structural gene. Furthermore, loss of CD5
      surface expression correlated with the absence of specific mRNA. Since these
      hybrids preferentially segregate human chromosomes, these results indicate the
      existence of a non-syntenic trans-active locus, or loci, positively controlling
      the expression of the human CD5 gene.

PMID- 7518802
TI  - Induction of mucosal and systemic immune responses by immunization with ovalbumin
      entrapped in poly(lactide-co-glycolide) microparticles.
AB  - We have examined the range of mucosal and systemic immune responses induced by
      oral or parenteral immunization with ovalbumin (OVA) entrapped in poly(D,L
      lactide-co-glycolide) (PLG) microparticles. A single subcutaneous immunization
      with OVA-PLG primed significant OVA-specific IgG and delayed-type
      hypersensitivity (DTH) responses. The DTH responses were of similar magnitude to
      those obtained using immunostimulating complexes (ISCOMS) as a potent control
      adjuvant, although ISCOMS stimulated higher serum IgG responses. Both vectors
      also primed OVA-specific in vitro proliferative responses in draining lymph node
      cells following a single immunization and strong OVA-specific CTL responses were
      found after intraperitoneal (i.p.) immunization. ISCOMS were more efficient in
      inducing cytotoxic T lymphocytes (CTL), requiring much less antigen and only
      ISCOMS could stimulate primary OVA-specific CTL responses in the draining lymph
      nodes. Multiple oral immunizations with OVA in PLG microparticles or in ISCOMS
      resulted in OVA-specific CTL responses and again ISCOMS seemed more potent as
      fewer feeds were necessary. Lastly, multiple feeds of OVA in PLG microparticles
      generated significant OVA-specific intestinal IgA responses. This is the first
      demonstration that PLG microparticles can stimulate CTL responses in vivo and our
      results highlight their ability to prime a variety of systemic and mucosal immune
      responses which may be useful in future oral vaccine development.

PMID- 7518805
TI  - Gamma benzene hexachloride neurotoxicity.

PMID- 7518804
TI  - Mutations inside but not outside the peptide binding cleft of the H-2 Ld molecule
      affect CTL recognition and binding of the nucleoprotein peptide from the
      lymphocytic choriomeningitis virus.
AB  - In order to investigate the role of residues inside and outside the peptide
      binding cleft of the Ld molecule in peptide presentation to cytotoxic T
      lymphocytes (CTL), we constructed a series of point mutations in the Ld gene. We
      determined the effects of the mutations in the Ld molecule on the binding and
      recognition of an Ld-restricted CTL epitope derived from the nucleoprotein (NP)
      of the lymphocytic choriomeningitis virus (LCMV). Each of the mutations within
      the Ld peptide binding cleft resulted in a complete loss of CTL recognition.
      Addition of the LCMV NP peptide to cells expressing these mutants did not
      increase surface Ld expression, suggesting that the mutations altered peptide
      binding. Mutations involving pockets D and E within the cleft affected LCMV
      peptide binding and recognition as drastically as those in pocket B, which was
      predicted to interact with a main anchor residue of the peptide. In striking
      contrast, the mutations located outside the cleft did not change either
      recognition or binding. These results demonstrate that the Ld residues in the
      peptide binding cleft are the main determinants dictating LCMV NP peptide
      binding, and that the residues in each of the pockets within the cleft play a
      role in this interaction. Surprisingly, one mutation outside the peptide binding
      cleft, T92S, abrogated CTL lysis of target cells treated with the LCMV NP
      peptide, but not virus-infected cells. These data show that this mutation
      selectively altered the presentation of the LCMV NP peptide introduced to the
      cell exogenously, but not endogenously. This implies that the pathway by which
      peptides associate with class I molecules within the cell differs from that of
      exogenous peptide binding.

PMID- 7518806
TI  - Molecular characterization of clustered variants of genes encoding major surface
      antigens of human Pneumocystis carinii.
AB  - A 13-kb genomic fragment from human Pneumocystis carinii was cloned as repetitive
      DNA. The fragment contains a cluster of three related genes, each 3 kb in size,
      and the 5' end of a fourth gene. The predicted polypeptide of the first gene in
      the cluster comprises 1,030 amino acid residues with a total molecular mass of
      116 kDa. The gene's predicted amino acid sequence bears 32% identity to predicted
      sequences of recently described gene fragments of ferret P. carinii, which encode
      an immunodominant surface glycoprotein (gpA) (P. J. Haidaris, T. W. Wright, F.
      Gigliotti, and C. G. Haidaris, J. Infect. Dis. 166:1113-1123, 1992), and 36%
      identity to the predicted sequence of a rat P. carinii major surface glycoprotein
      gene (msg) (J. A. Kovacs, F. Powell, J. C. Edman, B. Lundgren, A. Martinez, B.
      Drew, and C. W. Angus, J. Biol. Chem. 268:6034-6040). DNA hybridization showed
      that sequences related to the cloned msg genes reside on at least 12 chromosomes
      of human P. carinii at various degrees of multiplicity and/or homology. Affinity
      purified antibodies with specificity to a fusion protein made from the human P.
      carinii msgI gene recognized two bands on a Western immunoblot containing total
      human P. carinii protein; they also recognized fusion proteins derived from the
      other two genes of the cluster. Monoclonal antibodies with reactivity to Msg of
      human P. carinii recognized fusion proteins produced from two msg genes. Fusion
      proteins were also recognized by sera from healthy humans and from patients. The
      msg genes are candidates for the development of immunotherapy and subunit
      vaccines for the treatment and prevention of P. carinii pneumonia.

PMID- 7518808
TI  - Bovine T cells specific for Trypanosoma brucei brucei variant surface
      glycoprotein recognize nonconserved areas of the molecule.
AB  - The specificity of bovine CD4+ T-cell responses to Trypanosoma brucei variant
      surface glycoprotein (VSG) has been examined by using a panel of seven T-cell
      clones and nested deletions of the ILTat 1.3 VSG gene expressed in Escherichia
      coli. All clones recognized the polymorphic N-terminal domain of the antigen, and
      the recognition sites of five of the clones were resolved to three areas with
      lengths of 14, 18, and 21 amino acids. Comparison of these regions with
      corresponding areas of other VSG molecules, including those derived from the same
      trypanosomal serodeme, has shown that the sites are not conserved. In the light
      of recent observations that VSG-specific T-cell responses are induced in mice
      infected with T. brucei, these results confirm with the belief that immune
      pressure from T cells may contribute to the generation of antigenic diversity on
      the surface of African trypanosomes.

PMID- 7518807
TI  - Cytokine sensitivity and methylation of lysine in Rickettsia prowazekii EVir and
      interferon-resistant R. prowazekii strains.
AB  - Modified Rickettsia prowazekii strains have been derived from the avirulent
      Madrid E strain by passage in the lungs of white mice (strain EVir) or by
      selection for resistance to gamma interferon (IFN-gamma) (strains 427-19 and 87
      17) or alpha/beta interferon (IFN-alpha/beta) (strains 83-2P, 60P, 103-2P, and
      110-1P). Compared with the Madrid E strain, strain EVir has increased virulence
      (N. M. Balayeva and V. N. Nikolskaya, J. Hyg. Epidemiol. Microbiol. Immunol.
      17:11-20, 1973) and a different lysine methylation profile in its surface protein
      antigen (A. V. Rodionov, M. E. Eremeeva, and N. M. Balayeva, Acta Virol. 35:557
      565, 1991). The other six strains differ from the Madrid E strain in their
      resistance to IFN and their ability to grow well in untreated macrophagelike
      RAW264.7 cells. In the present study, to determine which properties are shared by
      these strains, we examined R. prowazekii EVir for the following: (i) the
      sensitivity of its growth in L929 cells to the cytokines IFN-alpha/beta, IFN
      gamma, tumor necrosis factor alpha (TNF-alpha), and IFN-gamma plus TNF-alpha;
      (ii) the ability to grow in untreated RAW264.7 cells; and (iii) the ability to
      induce interferon in L929 cell cultures; we also evaluated strains 83-2P and 87
      17 for lysine methylation. Multiplication of strain EVir in growing L929 cells
      was not markedly inhibited by either IFN-alpha/beta or IFN-gamma. In X-irradiated
      L929 cells, growth of strain EVir was slightly inhibited (11%) by TNF-alpha
      alone, somewhat inhibited (38%) by IFN-gamma alone, and markedly inhibited (87%)
      by IFN-gamma plus TNF-alpha. Nitrite production was induced in X-irradiated,
      strain EVir-infected L929 cell cultures treated with TNF-alpha alone or IFN-gamma
      alone; however, more nitrite was produced in infected cultures treated with IFN
      gamma plus TNF-alpha. Nitrite production, the dramatic inhibitory effect of IFN
      gamma plus TNF-alpha, and the modest inhibitory effect of IFN-gamma on the growth
      of strain EVir in X-irradiated L929 cells were all alleviated by the addition of
      the nitric oxide synthase inhibitor NG-methyl-L-arginine. Strain EVir grew very
      well in untreated macrophagelike RAW264.7 cells and appeared defective in the
      ability to induce IFN in L929 cell cultures. All strains grown in L929 cells in
      the presence of radiolabeled lysine had similar percentages of their
      radioactivity as methylated lysines.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7518811
TI  - Neuropeptides in psoriasis: possible role of beta-endorphin in the pathomechanism
      of the disease.
AB  - BACKGROUND: An increased concentration of neuropeptides in psoriatic lesional
      skin may be responsible for alterations in the neurogenic erythematous response
      and transmission of stimuli through sensory nerve fibers (sensation of pruritus).
      METHODS: Increasing doses of capsaicin from 0.125 to 4 micrograms/cm2 were
      applied to nonlesional psoriatic skin to establish the minimal dose that induced
      the substance P-mediated neurogenic response in 30 patients with psoriasis.
      Plasma beta-endorphin was quantitated in 71 psoriatics by radioimmunoassay using
      NEN 1251-RIA kit. RESULTS: The mean beta-endorphin concentration was increased
      about 2-fold compared to normals, whereas doses of capsaicin needed to induce
      erythema were higher (1-4 micrograms/cm2) in psoriatics (mainly in patients with
      type II psoriasis) than in healthy subjects (0.125-0.25 microgram/cm2).
      CONCLUSIONS: The data indicate that increased beta-endorphin in psoriatic skin
      might affect both substance P-mediated neurogenic inflammation and transmission
      of sensory stimuli due to local antinociceptive effects of this opioid. The
      differences in the neurogenic response in type I and II psoriasis may be related
      to the degradation of substance P and beta-endorphin by neutral proteinases in
      the lesional skin.

PMID- 7518810
TI  - Interstrain conservation of babesial RAP-1 surface-exposed B-cell epitopes
      despite rap-1 genomic polymorphism.
AB  - Members of the babesial rhoptry-associated protein 1 (RAP-1) family express
      surface-exposed B-cell epitopes and are candidate antigens for vaccine
      development. The relationship between rap-1 genomic polymorphism and surface
      exposed B-cell epitope expression was analyzed by comparison of biological clones
      of Mexico strain Babesia bigemina and Babesia bovis with strains isolated in
      Argentina. Despite genomic polymorphism between strains, including sequences
      located within the open reading frame, defined RAP-1 B-cell surface epitopes and
      RAP-1 molecular size were conserved in both B. bovis and B. bigemina.

PMID- 7518809
TI  - Distinct binding properties of eaeA-negative verocytotoxin-producing Escherichia
      coli of serotype O113:H21.
AB  - Infection of humans with verotoxin-producing Escherichia coli (VTEC) O113:H21 is
      associated with clinical features comparable to those associated with infection
      with attaching and effacing VTEC strains including those of serotype O157:H7. We
      have shown previously that the adhesion phenotype of VTEC O157:H7 is influenced
      by the presence of a homolog of the chromosomal eaeA (for E. coli attaching and
      effacing) gene. In contrast, by colony blot hybridization, VTEC O113:H21 is
      negative for the eaeA gene. Therefore, the aim of this study was to define the
      adhesion phenotype of VTEC O113:H21 strain CL-15 to both cultured epithelial
      cells (HEp-2) and rabbit intestine in vivo. Under transmission electron
      microscopy, areas of microvillus effacement were observed in regions directly
      beneath the organism in CL-15-infected cells both in vitro and in vivo. However,
      F-actin adhesion pedestals on the host plasma membrane were absent. Failure of CL
      15 to induce polymerization of actin was confirmed by using staining of F-actin
      with fluorescein-labeled phalloidin. Under indirect immunofluorescence
      microscopy, CL-15-infected HEp-2 cells also failed to demonstrate the recruitment
      of another cytoskeletal element, alpha-actinin, below foci of bacterial adhesion.
      In contrast, VTEC O157:H7 infection of HEp-2 cells was associated with increased
      alpha-actinin immunofluorescence. These findings suggest that bacterial factors
      distinct from those of EaeA are necessary for the adhesion phenotype of VTEC
      O113:H21.

PMID- 7518812
TI  - Monocyte adhesion to fibronectin in psoriasis.
AB  - BACKGROUND: After vascular extravasation, mononuclear cells (MNC) undergo
      chemotaxis and adhesion to extracellular matrix proteins, resulting in their
      differentiation into macrophages. Although endothelial adhesion and chemotaxis
      are altered in psoriasis, MNC adhesion to extracellular matrix proteins has not
      been previously studied in the disease. Since MNC adhesion to endothelial cells
      is abnormally regulated in psoriasis by TGF-beta, we tested they hypothesis that
      in psoriasis substance P also regulates the adhesion of monocytes to the
      extracellular matrix protein fibronectin. METHODS: Monocytes from 16 normal
      controls and 11 psoriatic individuals were isolated and purified using a two-step
      gradient centrifugation procedure. Adhesion to fibronectin was studied by plating
      monocyte suspensions onto fibronectin-precoated microtiter plates. The number of
      adherent cells was quantified by measuring their hexosaminidase activity.
      RESULTS: Although statistically significant differences in the basal
      (unstimulated) adhesion or in the substance P-stimulated adhesion between normal
      control monocytes and those obtained from psoriatic individuals were not
      observed, a subpopulation of psoriatics was identified who responded to substance
      P. Furthermore, this in vitro response to substance P was correlated with the
      clinical status of the subpopulation which was characterized by unstable
      psoriasis triggered by stressful life events. CONCLUSIONS: The results of this
      study indicate that priming of monocytes by the extracellular matrix protein
      fibronectin or by elevated levels of substance P are not critical steps in the
      pathogenesis of stable, chronic psoriasis. Substance P may contribute to the
      appearance of new lesions in some individuals with unstable psoriasis.

PMID- 7518813
TI  - A dual immunocytochemical assay for oestrogen and epidermal growth factor
      receptors in tumour cell lines.
AB  - A new dual immunocytochemical assay for oestrogen receptor (ER) and epidermal
      growth factor receptor (EGFR) has been developed. It has been tested in a variety
      of conditions using cell culture lines and the results correlate well with those
      obtained from single immunocytochemical assays. MCF-7 and A431 cells and a
      mixture of the two types of cell were assessed immunocytochemically for ER and
      EGFR. ER showed immunopositivity of 30% in MCF-7 cells, 10% in the mixture and 0%
      in A431 cells. EGFR demonstrated immunopositivity of 0% in MCF-7 cells, 70% in
      the mixture and 100% in A431 cells. Dual immunocytochemical assays using anti-ER
      followed by anti-EGFR monoclonal antibodies on single histological sections
      showed similar reactivity to the single assays. Three staining patterns were seen
      in the mixture: ER+/EGFR- (MCF-7 cells), ER-/EGFR- (MCF-7 cells) and ER-/EGFR+
      (A431 cells). ZR-75-1 and MDA-MB-231 cells and their retrovirally transfected
      counterparts ZR/HERc and MDA/HEGO cells were then analysed. The dual assay
      revealed the fourth phenotype (ER+/EGFR+) in 40% of ZR/HERc cells and in 10% of
      MDA/HEGO cells. This is the first description of a dual immunocytochemical assay
      system for ER and EGFR on single 5 microns frozen section samples. Studies are
      now underway assessing breast carcinoma sections which may allow investigation of
      the clonality of human breast cancer.

PMID- 7518814
TI  - Production and characterization of a monoclonal antibody against human calcitonin
      gene-related peptide (CGRP) and its immunohistochemical application to salivary
      glands.
AB  - A monoclonal antibody (mAb), 129CD8 was raised against a C-terminal fragment
      (aa28-37) of alpha-human calcitonin gene-related peptide (CGRP) coupled to bovine
      serum albumin. The specificity of the monoclonal antibody 129CD8 was corroborated
      by dot immunobinding experiments, enzyme-linked immunoassay and immunostaining of
      tissue sections. In vitro studies showed that the mAb 129CD8 readily recognized
      the fragment 28-37 of alpha-human CGRP and to a slightly lesser degree whole
      alpha-human CGRP and the fragments containing the C-terminal part of the
      molecule. The mAb 129CD8 also recognized the beta-human CGRP but not the alpha
      rat CGRP. The mAb 129CD8 did not react with substance P, katacalcin, calcitonin,
      amylin or fragments of alpha-human CGRP lacking the C-terminal part of the
      molecule. Immunocytochemical staining was performed on human skin, guinea-pig
      thyroid and salivary glands and the trigeminal ganglion, and rat thyroid gland.
      Our findings demonstrate, in keeping with previous studies, that in human skin,
      nerve fibres containing CGRP immunoreactivity are found in both epidermis and
      dermis. In accordance with previous investigators, the Merkel cells were
      immunoreactive for CGRP. In the guinea-pig and rat thyroid gland CGRP
      immunoreactivity was localized in the C-cells. The distribution of CGRP
      immunoreactivity in the guinea-pig salivary glands is different from that
      previously reported for rat salivary glands. In the guinea-pig trigeminal
      ganglion, CGRP immunoreactivity was localized mainly in small-sized neurons and
      fibres traversing the ganglion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518816
TI  - Regarding "Technical and tumor-related factors affecting outcome of definitive
      irradiation for localized carcinoma of the prostate".

PMID- 7518815
TI  - Results of combined external irradiation and chemotherapy of bleomycin or
      peplomycin for squamous cell carcinomas of the lower gingiva.
AB  - PURPOSE: In Japan, the role of radiotherapy for gingival carcinomas has not been
      considered as a radical treatment, but only a pre and/or postoperative treatment.
      This study was aimed to discuss a possibility of radiotherapy for a radical
      treatment. In this study, radiotherapy was given as an initial treatment for
      squamous cell carcinomas of the lower gingiva in simultaneous combination with
      chemotherapy of bleomycin or peplomycin (Tokyo, Japan). METHODS AND MATERIALS:
      When complete regression of the tumor was obtained, subsequent surgery was
      postponed with or without a booster of radiotherapy of about 30 Gy until a
      recurrent lesion was confirmed. RESULTS: Sixty-seven percent of 100 patients with
      T1 or T2 had complete regression, while only 22 (35.5%) of 62 patients with T3 or
      T4 had complete regression. The 5-year local control rate by T classification,
      including the results of secondary treatments (surgery and/or radiotherapy and/or
      chemotherapy) for recurrent lesions, was 91% for T1, 89% for T2, 76% for T3 and
      61% for T4. The 5-year local control rate according to treatment methods was 95%
      in the group without surgery and 86% in the group with surgery for T1 and T2
      patients. The rates were 54% and 71%, respectively for T3 and T4 patients. The
      cause specific 5-year survival rate by stage was 75% for Stage I, 87% for Stage
      II, 71% for Stage III, 51% for Stage IV and 70% overall. CONCLUSION: The
      combination of radiotherapy and chemotherapy could be a conservative radical
      treatment for T1 and T2 patients with lower gingival carcinoma.

PMID- 7518817
TI  - G-CSF treatment of leucopenia during fractionated radiotherapy.

PMID- 7518818
TI  - Benzomalvins, new substance P inhibitors from a Penicillium sp.
AB  - In the course of screening microbial broths for neurokinin receptor antagonists,
      a series of new benzodiazepines, benzomalvins A (1), B (2) and C (3), has been
      isolated from the culture broth of a fungus identified as a Penicillium sp.
      Benzomalvin A (1) showed inhibitory activity against substance P with Ki values
      of 12, 42 and 43 microM at the guinea pig, rat and human neurokinin NK1
      receptors, respectively. Benzomalvins B (2) and C (3) were only weakly active.
      The structures of these compounds were determined by spectroscopic methods
      including MS measurements and NMR analysis.

PMID- 7518819
TI  - Time course of endolymph volume increase in experimental hydrops measured in vivo
      with an ionic volume marker.
AB  - A new method has been developed to measure the cross-sectional area (CSA) of
      scala media in the living cochlea. The method has some advantages over
      histological methods, in which tissues may shrink or move during processing. In
      the present study, scala media CSA was measured in the second turn of guinea-pig
      cochleas in which endolymphatic hydrops was induced surgically. The area
      measurement method used an iontophoretic injection of a volume marker into scala
      media, during which the concentration of marker in endolymph was monitored with
      an ion-selective microelectrode. The measured marker concentration was inversely
      proportional to the CSA of endolymph. The marker we used was the anion arsenic
      hexafluoride (AsF6-), which was almost ideal for the purpose as it was retained
      well in endolymph. Area was measured in normal animals and in hydropic animals at
      times from 4 days to 16 weeks after endolymphatic duct obstruction. The results
      showed that hydrops develops within days of ablation of the endolymphatic duct.
      The degree of hydrops was compared with electrophysiological measures of
      function, including the endocochlear potential, action potential thresholds and
      the amplitudes of the cochlear microphonic, summating potential and action
      potentials. In the initial stages of hydrops development, electrophysiological
      changes were small. In contrast, there were marked functional changes between 8
      and 16 weeks, when endolymph volume was no longer increasing. If the same is true
      for dysfunction in the ears of patients with Meniere's Disease, then it may not
      be possible to restore normal function simply by alleviating the
      hydrops.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518820
TI  - Brief report: an analysis of subject characteristics in research reported in the
      Journal of Autism and Developmental Disorders 1982-1991.

PMID- 7518821
TI  - Regulation of insulin-like growth factor 1 binding protein 3 levels by epidermal
      growth factor and retinoic acid in cervical epithelial cells.
AB  - Insulin-like growth factors (IGFs) are important regulators of epithelial cell
      growth. The mitogenic activity of these factors is influenced by the levels of
      extracellular IGF binding proteins, including insulin-like growth factor binding
      protein 3 (IGFBP-3). In the present report we study the effects of epidermal
      growth factor (EGF) and all-trans-retinoic acid (RA) on IGFBP-3 RNA and protein
      levels in human papillomavirus-immortalized cervical epithelial cells. Treatment
      of ECE16-1 cells with 3-20 ng/ml EGF causes a marked reduction in IGFBP-3 levels.
      In contrast, 1 microM RA increases IGFBP-3 mRNA and protein levels in the
      presence or absence of 20 ng/ml EGF. The response is concentration dependent with
      a half-maximal increase observed at 1 nM RA. RA is able to reverse the EGF
      suppression when added simultaneously or 3 days after initiation of EGF
      treatment. Conversely, when cells are treated with RA, IGFBP-3 levels increase
      within 24 h and subsequent addition of EGF is without effect. Thus, the RA
      dependent increase in IGFBP-3 levels is dominant over the EGF suppression. The
      increased IGFBP-3 levels are correlated with RA suppression of proliferation.
      Similar RA effects on IGFBP-3 mRNA levels were observed in other cervical
      epithelial cell lines (i.e., ECE16-D1, ECE16-D2, and CaSki). These results
      suggest that RA may act to inhibit cervical cell growth by increasing IGFBP-3
      levels and reducing the extracellular concentration of free insulin-like growth
      factor I (IGFI) and/or alternatively, IGFBP-3 may inhibit cell growth by direct
      effects on the cell, independent of IGFI.

PMID- 7518822
TI  - Binding and degradation of hyaluronan by human breast cancer cell lines
      expressing different forms of CD44: correlation with invasive potential.
AB  - In the present study, we examined a panel of human breast cancer cell lines with
      regard to their expression of CD44 and ability to bind and degrade hyaluronan.
      The cell lines expressed varying amounts of different molecular weight forms of
      CD44 (85-200 kDa) and, in general, those that expressed the greatest amounts of
      CD44 were the most invasive as judged by in vitro assays. In addition, the
      ability to bind and degrade hyaluronan was restricted to the cell lines
      expressing high levels of CD44, and both these functions were blocked by an
      antibody to CD44 (Hermes-1). Moreover, the rate of [3H]hyaluronan degradation was
      highly correlated with the amount of CD44 (r = 0.951, P < 0.0001), as well as
      with the invasive potential of the cells. Scatchard analysis of the
      [3H]hyaluronan binding of these cells revealed the existence of significant
      differences in both their binding capacity and their dissociation constant. To
      determine the source of this deviation, the different molecular weight forms of
      CD44 were partially separated by gel filtration chromatography. In all cell
      lines, the 85 kDa form was able to bind hyaluronan, although with different
      affinities. In contrast, not all of the high molecular weight forms of CD44 had
      this ability. These results illustrate the diversity of CD44 molecules in
      invasive tumor cells, and suggest that one of their major functions is to degrade
      hyaluronan.

PMID- 7518823
TI  - SR 25989 inhibits healing of a mechanical wound of confluent human saphenous vein
      endothelial cells which is modulated by standard heparin and growth factors.
AB  - The thienopyridine, ticlopidine, a potent platelet antiaggregating agent and SR
      25989, an esterified derivative of ticlopidine, devoid of antiplatelet activity,
      were tested in an in vitro model of healing of a mechanical wound in confluent
      endothelium. This model allows exploration of substances involved in wound
      healing and angiogenesis. These two compounds inhibited both cell proliferation
      and cell migration during lesion repair in a dose-dependent manner (18-150
      microM), SR 25989 being twice as active as ticlopidine. Its effect was not
      inhibited by acidic or basic fibroblast growth factor or by platelet derived
      growth factor. In contrast, it exerted a conjugated inhibition with standard
      heparin and was able to totally reverse the healing increase induced by a mixture
      of acidic fibroblast growth factor and heparin. The mechanism of action of SR
      25989 is not yet elucidated, but it does not seem to involve competition with
      fibroblast growth factors since these substances were not able to alter their
      binding to receptors on the endothelial cell surface. SR 25989 therefore appears
      as a promising new candidate for inhibition of angiogenesis.

PMID- 7518825
TI  - Contrasting infant predictors of later cognitive functioning.
AB  - The predictive power of early visual attention in terms of later cognitive
      functioning was compared to standard developmental test scores and further early
      predictors of later development. In a longitudinal study of 226 infants at risk
      visual attention in a habituation-dishabituation paradigm was assessed at 3
      months and cognitive development was measured at 3, 24 and 54 months. The results
      indicated that response decrement and response recovery measures are related to
      cognitive outcome in later childhood, but failed to support their superiority
      over standard developmental test scores or early biological and psychosocial
      predictors of later IQ. Methodological shortcomings of previous studies and
      theoretical weaknesses of the habituation concept were discussed as a possible
      explanation.

PMID- 7518824
TI  - Heterogeneity and contact-dependent regulation of amylase release by individual
      acinar cells.
AB  - We have used a reverse hemolytic plaque assay to investigate the amylase release
      of single and aggregated pancreatic acinar cells. We have found that a minority
      of single acinar cells released detectable amounts of amylase under basal
      conditions and were modestly stimulated, in a dose-dependent manner, during a 30
      min exposure to concentrations of carbamylcholine (CCh) ranging from 10(-8) to
      10(-5) M. This stimulation was largely accounted for by the recruitment of
      additional secreting cells, rather than by a significant increase in their
      individual secretory output. We have also observed that aggregates comprising two
      to five acinar cells secreted more frequently and released more amylase than
      single acinar cells in the presence of each of the CCh concentrations tested.
      Under both basal conditions and following CCh stimulation, the proportion of
      secreting aggregates and their amylase output increased linearly with the
      aggregate size. Under basal conditions as well as in the presence of secretagogue
      concentrations in the 10(-8) - 10(-7) M range, individual cells contributed
      similarly to amylase secretion whether they were single or part of aggregates. By
      contrast, following stimulation by 10(-6) - 10(-5) M CCh, aggregated cells showed
      a much higher average secretion than single cells. Investigating the mechanism of
      this contact-dependent effect, we found that 10(-3) M heptanol did not
      significantly modify the secretion of single cells and markedly promoted the
      basal amylase release of acinar cell pairs. This effect was associated with a
      marked reduction in gap junctional communication between acinar cells, as
      evaluated by microinjection of Lucifer yellow, and was not observed during
      exposure to high concentrations of CCh, which also reduced junctional
      communication. These data show that pancreatic acinar cells are intrinsically
      heterogeneous in their ability to release amylase and that their basal as well as
      stimulated secretion are promoted by the establishment of direct intercellular
      contacts. Our experiments also suggest that junctional coupling contributes to
      the contact-dependent mechanism which enhances the recruitment of secreting cells
      and their individual output. These observations strengthen the view that direct
      interactions between acinar cells are essential in the control of pancreatic
      secretion.

PMID- 7518826
TI  - Analysis of environmental deprivation: cognitive and social development in
      Romanian orphans.
AB  - The cognitive and social developmental status of a representative group of
      Romanian orphans between the ages of 23 and 50 months living in the Leagan de
      Copii in Timisoara, Romania was assessed using a variety of traditional and
      nontraditional measures. Results indicated that the orphanage sample all
      exhibited deficits in cognitive and social functioning; the majority were
      severely delayed. Correlations between the traditional and nontraditional
      measures indicated that children's delays occurred across domains. Deficits were
      not related to length of time in the orphanage, age at entrance, Apgar scores, or
      birthweight. The children's greatest capability was in peer social interaction.

PMID- 7518827
TI  - Myelin in multiple sclerosis is developmentally immature.
AB  - The etiology of multiple sclerosis (MS) is considered to involve genetic,
      environmental, infective, and immunological factors which affect the integrity of
      a normally assembled myelin sheath, either directly or indirectly resulting in
      demyelination. In a correlative study involving protein chemical, mass
      spectrometric, and electron microscopic techniques we have determined that myelin
      obtained from victims of MS is arrested at the level of the first growth spurt
      (within the first 6 yr of life) and is therefore developmentally immature. The
      data supporting this conclusion include (a) the pattern of microheterogeneity of
      myelin basic protein (MBP); (b) the NH2-terminal acylation of the least cationic
      component of MBP ("C-8"); (c) the phase transition temperature (Tc) of myelin
      isolated from victims of MS correlated with the increased proportion of the least
      cationic component of MBP; and (d) immunogold electron microscopy using an
      antibody specific for "C-8" showed that the distribution of gold particles in a 2
      yr-old infant was similar to the distribution found in a victim of MS. We
      postulate that this developmentally immature myelin is more susceptible to
      degradation by one or a combination of factors mentioned above, providing the
      initial antigenic material to the immune system.

PMID- 7518828
TI  - Tumor necrosis factor-alpha inhibits stem cell factor-induced proliferation of
      human bone marrow progenitor cells in vitro. Role of p55 and p75 tumor necrosis
      factor receptors.
AB  - Stem cell factor (SCF), a key regulator of hematopoiesis, potently synergizes
      with a number of hematopoietic growth factors. However, little is known about
      growth factors capable of inhibiting the actions of SCF. TNF-alpha has been shown
      to act as a bidirectional regulator of myeloid cell proliferation and
      differentiation. This study was designed to examine interactions between TNF
      alpha and SCF. Here, we demonstrate that TNF-alpha potently and directly inhibits
      SCF-stimulated proliferation of CD34+ hematopoietic progenitor cells.
      Furthermore, TNF-alpha blocked all colony formation stimulated by SCF in
      combination with granulocyte colony-stimulating factor (CSF) or CSF-1. The
      synergistic effect of SCF observed in combination with GM-CSF or IL-3 was also
      inhibited by TNF-alpha, resulting in colony numbers similar to those obtained in
      the absence of SCF. These effects of TNF-alpha were mediated through the p55 TNF
      receptor, whereas little or no inhibition was signaled through the p75 TNF
      receptor. Finally, TNF-alpha downregulated c-kit cell-surface expression on CD34+
      bone marrow cells, and this was predominantly a p55 TNF receptor-mediated event
      as well.

PMID- 7518829
TI  - Cystic fibrosis transmembrane conductance regulator mutations that disrupt
      nucleotide binding.
AB  - Increasing evidence suggests heterogeneity in the molecular pathogenesis of
      cystic fibrosis (CF). Mutations such as deletion of phenylalanine at position 508
      (delta F508) within the cystic fibrosis transmembrane conductance regulator
      (CFTR), for example, appear to cause disease by abrogating normal biosynthetic
      processing, a mechanism which results in retention and degradation of the mutant
      protein within the endoplasmic reticulum. Other mutations, such as the relatively
      common glycine-->aspartic acid replacement at CFTR position 551 (G551D) appear to
      be normally processed, and therefore must cause disease through some other
      mechanism. Because delta F508 and G551D both occur within a predicted nucleotide
      binding domain (NBD) of the CFTR, we tested the influence of these mutations on
      nucleotide binding by the protein. We found that G551D and the corresponding
      mutation in the CFTR second nucleotide binding domain, G1349D, led to decreased
      nucleotide binding by CFTR NBDs, while the delta F508 mutation did not alter
      nucleotide binding. These results implicate defective ATP binding as contributing
      to the pathogenic mechanism of a relatively common mutation leading to CF, and
      suggest that structural integrity of a highly conserved region present in over 30
      prokaryotic and eukaryotic nucleotide binding domains may be critical for normal
      nucleotide binding.

PMID- 7518830
TI  - Changes in cartilage metabolism in arthritis are reflected by altered serum and
      synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for
      pathogenesis.
AB  - The metabolism of the cartilage proteoglycan aggrecan was studied in patients
      with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in
      controls (n = 117) using monoclonal antibody-based radioimmunoassays for
      glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on
      chondroitin sulfate (probably only on recently synthesized molecules) and a
      keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules.
      Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and
      8.6-fold in RA) being highest in OA patients with the longest disease duration
      and greatest loss of cartilage, and lowest in RA joints with high leucocyte
      counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and
      probably reflect increased aggrecan synthesis in diseased joints. KS levels were
      higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were
      inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was
      reduced in both diseases and in RA was inversely related to both systemic and
      joint inflammation markers. SF 846 levels were inversely related to SF KS in both
      diseases. These epitopes may provide a measure of the balance between cartilage
      synthesis and degradation in these diseases.

PMID- 7518831
TI  - Biphasic induction of immediate early gene expression accompanies activity
      dependent angiogenesis and myofiber remodeling of rabbit skeletal muscle.
AB  - Sustained contractile activity of skeletal muscle promotes angiogenesis, as well
      as transformation of contractile protein isoforms and mitochondrial proliferation
      within myofibers. Since the products of immediate early genes such as c-fos, c
      jun, and egr-1 function in many signaling pathways governing cellular responses
      to external stimuli, we sought to determine whether sustained contractile
      activity induces their expression in skeletal muscle. Low voltage electrical
      stimulation was applied to the motor nerve innervating rabbit tibialis anterior
      muscles for periods ranging from 45 min to 21 d. Northern and Western analysis
      demonstrated marked but transient inductions of c-fos, c-jun, and egr-1 mRNA and
      protein within the first 24 h. Longer durations of stimulation were associated
      with a secondary and sustained rise in the abundance of c-fos, c-jun, and p88egr
      1 protein that, surprisingly, was not accompanied by detectable changes in mRNA.
      Immunohistochemistry demonstrated c-fos immunoreactivity within myofiber and
      vascular cell nuclei during both early and late phases of this response. These
      findings reveal a complex pattern of c-fos, c-jun, and egr-1 expression in
      response to nerve stimulation and suggest that these proteins could function in
      regulatory pathways that modify muscle phenotype.

PMID- 7518832
TI  - Maternal immunization of mice with group B streptococcal type III polysaccharide
      beta C protein conjugate elicits protective antibody to multiple serotypes.
AB  - Group B streptococcal infection is a major cause of neonatal mortality. Antibody
      to the capsular polysaccharide protects against invasive neonatal disease, but
      immunization with capsular polysaccharides fails to elicit protective antibody in
      many recipients. Conjugation of the polysaccharide to tetanus toxoid has been
      shown to increase immune response to the polysaccharide. In animal models, C
      proteins of group B streptococci are also protective determinants. We examined
      the ability of the beta C protein to serve in the dual role of carrier for the
      polysaccharide and protective immunogen. Type III polysaccharide was covalently
      coupled to beta C protein by reductive amination. Immunization of rabbits with
      the polysaccharide-protein conjugate elicited high titers of antibody to both
      components, and the serum induced opsonophagocytic killing of type III, Ia/C, and
      Ib/C strains of group B streptococci. Female mice were immunized with the
      conjugate vaccine and then bred; 93% of neonatal pups born to these dams
      vaccinated with conjugate survived type III group B streptococcal challenge and
      76% survived type Ia/C challenge, compared with 3% and 8% survival, respectively,
      in controls (P < 0.001). The beta C protein acted as an effective carrier for the
      type III polysaccharide while simultaneously induced protective immunity against
      beta C protein--containing strains of group B streptococci.

PMID- 7518833
TI  - Growth hormone promotes human T cell adhesion and migration to both human and
      murine matrix proteins in vitro and directly promotes xenogeneic engraftment.
AB  - Recombinant human growth hormone (rhGH) promotes human T cell engraftment in mice
      with severe combined immunodeficiency, suggesting that rhGH may have effects on T
      cell adhesion and migration in vivo. The ability of rhGH to directly affect the
      adhesion capacity of human T cells to a variety of human or murine adhesion
      molecules and extracellular matrix proteins was examined. rhGH induced
      significant human T cell adherence to both human and murine substrates via either
      beta 1 or beta 2 integrin molecules. rhGH was capable of inducing significant
      migration of resting and activated human T cells and their subsets. Most of the
      migratory response to rhGH was chemokinetic rather than chemotactic. In vivo
      engraftment studies in severe combined immunodeficiency mice receiving human T
      cells revealed that treatment with rhGH resulted in improved thymic engraftment,
      whereas treatment with non-human-reactive ovine GH demonstrated no significant
      effects. These data demonstrate that rhGH directly augments human T cell
      trafficking to peripheral murine lymphoid tissues. rhGH appears to be capable of
      directly altering the adhesive and migratory capacity of human T cells to
      molecules of either murine or human origin. Therefore, GH may, under either
      isogeneic or xenogeneic conditions, play a role in normal lymphocyte
      recirculation.

PMID- 7518834
TI  - Distinct roles of erythropoietin, insulin-like growth factor I, and stem cell
      factor in the development of erythroid progenitor cells.
AB  - Erythropoietin (EP), insulin-like growth factor I (IGF-I) and stem cell factor
      (SCF) each reduce apoptosis of human erythroid progenitor cells. To determine if
      these growth factors have additional roles in stimulating erythropoiesis, the
      proliferation, maturation, and survival of highly purified human erythroid colony
      forming cells (ECFCs) were studied during the application of different
      combinations of these growth factors in a serum-free liquid culture. EP
      maintained cell viability and supported heme synthesis during erythroid
      maturation, with little increase in viable cell number or stimulation of DNA
      synthesis. The addition of SCF with EP resulted in a substantial increase in DNA
      synthesis, which was greater than that seen with the addition of EP and was
      associated with a large expansion in the number of ECFCs. Thus EP, by itself,
      produces little increase in cell proliferation, and expansion of the number of
      erythroid cells depends upon the presence of SCF with EP. The addition of IGF-I
      with EP led to enhanced heme synthesis and moderate cellular proliferation, but
      also greatly enhanced nuclear condensation and enucleation in the late
      erythroblasts. Thus EP, by itself, is not sufficient for complete end-terminal
      nuclear condensation/enucleation and the presence of IGF-I is necessary for this
      complete process. While EP greatly reduced apoptosis during 16 h of incubation at
      37 degrees C, the addition of SCF and IGF-I with EP had little additional effect,
      but these additions enhanced DNA synthesis > 3.4-fold. Thus SCF may have an
      additional role in directly stimulating proliferation through a process that is
      distinct from apoptosis. Our observations indicate that EP prevents apoptosis and
      maintains erythroid cell viability and development. IGF-I enhances erythroid
      maturation and proliferation, but the proliferation of erythroid progenitors is
      mainly controlled by the addition of SCF with EP, independent of an effect on
      apoptosis.

PMID- 7518835
TI  - Interferon-alpha restores normal adhesion of chronic myelogenous leukemia
      hematopoietic progenitors to bone marrow stroma by correcting impaired beta 1
      integrin receptor function.
AB  - Treatment of chronic myelogenous leukemia (CML) with interferon-alpha frequently
      results in normalization of peripheral blood counts and, in up to 20% of
      patients, reestablishment of normal hematopoiesis. We hypothesize that interferon
      alpha may restore normal adhesive interactions between CML progenitors and the
      bone marrow microenvironment and restore normal growth regulatory effects
      resulting from these progenitor-stroma interactions. We demonstrate that
      treatment with interferon-alpha induces a significant, dose-dependent increase in
      the adhesion of primitive long-term culture initiating cells and committed colony
      forming cells (CFC) from CML bone marrow to normal stroma. Adhesion of CFC seen
      after interferon-alpha treatment could be inhibited by blocking antibodies
      directed at the alpha 4, alpha 5, and beta 1 integrins and vascular cell adhesion
      molecule, but not CD44 or intracellular adhesion molecule, suggesting that
      interferon-alpha induces normalization of progenitor-stroma interactions in CML.
      Because FACS analysis showed that the level of alpha 4, alpha 5, and beta 1
      integrin expression after interferon-alpha treatment is unchanged, this suggests
      that interferon-alpha may restore normal beta 1 integrin function. Normalization
      of interactions between CML progenitors and the bone marrow microenvironment may
      then result in the restoration of normal regulation of CML progenitor
      proliferation, and explain, at least in part, the therapeutic efficacy of
      interferon-alpha in CML.

PMID- 7518836
TI  - Interleukin 10 induces B lymphocytes from IgA-deficient patients to secrete IgA.
AB  - We have previously shown that human B lymphocytes cultured in the CD40 system,
      composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell
      line, proliferate but do not secrete antibodies. However, the addition of
      particles of Staphylococcus aureus Cowan (SAC) induces B cell differentiation
      even in the absence of exogenous cytokines (CD40/SAC system). Additionally, B
      lymphocytes cultured in the CD40 system in the presence of human IL-10, produce
      IgM, IgG, and IgA, and Ig levels are further increased by SAC. Here, we have
      studied the capacity of peripheral blood lymphocytes from patients with IgA
      deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering.
      Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the
      CD40/SAC system produced IgM and IgG, but not IgA. The addition of IL-10 to the
      cultures, enhanced the production of IgM and IgG and most strikingly induced the
      production of high amounts of IgA. The addition of IL-10 to PBMNC from IgA-D
      patients activated through CD40 alone resulted in the production of IgA. Thus,
      SAC and anti-CD40 mAb stimulate B cells to differentiate into cells secreting IgG
      and IgM whereas IL-10 plays a central role in inducing B cells from IgA-D
      patients to differentiate into IgA secreting cells.

PMID- 7518837
TI  - Prolonged impairment of very late activating antigen-mediated T cell
      proliferation via the CD3 pathway after T cell-depleted allogeneic bone marrow
      transplantation.
AB  - One of the major obstacles in allogeneic bone marrow transplantation (allo-BMT)
      is prolonged T cell dysfunction resulting in a variety of infectious
      complications in the months to years after hematologic engraftment. We previously
      showed that immobilized extracellular matrix (ECM) proteins such as fibronectin
      (FN), the CS-1 domain of FN, or collagen (CO) acted synergistically with
      immobilized anti-CD3 to induce T cell proliferation. In addition, the comitogenic
      effect of ECMs could be mimicked by immobilized mAb reactive with a common beta 1
      chain (CD29) of very late activating (VLA) antigens which include ECM receptors.
      Since the interaction of T cells with ECMs appears to play an important role in
      the process of T cell reconstitution following allo-BMT, we examined the
      expression of VLA antigens (alpha 1-alpha 6, beta 1) and their functional roles
      in CD3-mediated T cell proliferation at various times after T cell depleted allo
      BMT. VLA beta 1 as well as VLA alpha 4, alpha 5, and alpha 6 expression was lower
      than normal controls during the first 3 mo after allo-BMT and auto-BMT, whereas
      these expressions returned to normal levels by 4 mo after allo-BMT and auto-BMT.
      Although alpha 1 and alpha 2 were not expressed on lymphocytes from normal
      controls, these antigens were expressed on lymphocytes at the detectable levels
      (5-15%) from patients after allo-BMT and auto-BMT. Both CD29 and CD3 were
      expressed at normal levels on lymphocytes from patients > 3 mo after allo-BMT,
      whereas T cell interaction with ECM through VLA proteins or crosslinking of VLA
      beta 1 expressed by T cells with anti-CD29 mAb results in poor induction of CD3
      mediated T cell proliferation for a prolonged period (> 1 yr) after allo-BMT. In
      contrast, T cell proliferation induced by crosslinking of anti-CD2 or anti-CD26
      with anti-CD3 was almost fully recovered by 1 yr post-allo-BMT. After autologous
      BMT, impaired VLA-mediated T cell proliferation via the CD3 pathway after auto
      BMT returned to normal levels within 1 yr despite no significant difference in
      CD3 and CD29 expression following either allo- or auto-BMT. The adhesion of T
      cells from post-allo-BMT patients to FN-coated plate was normal or increased
      compared to that of normal controls. Moreover, the induction of the tyrosine
      phosphorylation of pp105 protein by the ligation of VLA molecules was not
      impaired in allo-BMT patients. These results suggest that there are some other
      defects in the process of VLA-mediated signal transduction in such patients. Our
      results imply that disturbance of VLA function could explain, at least in part,
      the persistent immunoincompetent state after allo-BMT and may be involved in
      susceptibility to opportunistic infections after allo-BMT.

PMID- 7518838
TI  - Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured
      human endothelial cells.
AB  - Antioxidants have been proposed to be anti-atherosclerotic agents; however, the
      mechanisms underlying their beneficial effects are poorly understood. We have
      examined the effect of alpha-tocopherol (alpha-tcp) on one cellular event in
      atherosclerotic plaque development, monocyte adhesion to stimulated endothelial
      cells (ECs). Human umbilical vein ECs were pretreated with alpha-tcp before
      stimulation with known agonists of monocyte adhesion: IL-1 (10 ng/ml), LPS (10
      ng/ml), thrombin (30 U/ml), or PMA (10 nM). Agonist-induced monocytic cell
      adhesion, but not basal adhesion, was inhibited in a time- and concentration
      dependent manner by alpha-tcp. The IC50 of alpha-tcp on an IL-1-induced response
      was 45 microM. The inhibition correlated with a decrease in steady state levels
      of E-selectin mRNA and cell surface expression of E-selectin which is consistent
      with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell
      adhesion in this system. Probucol (50 microM) and N-acetylcysteine (20 mM) also
      inhibited agonist-induced monocytic cell adhesion; whereas, several other
      antioxidants had no significant effect. Protein kinase C (PKC) does not appear to
      play a role in the alpha-tcp effect since no suppression of phosphorylation of
      PKC substrates was observed. Activation of the transcription factor NF-kappa B is
      reported to be necessary but not sufficient for E-selectin expression in EC.
      Electrophoretic mobility shift assays failed to show an alpha-tcp-induced
      decrease in activation of this transcription factor after cytokine stimulation.
      It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule
      by inhibiting generation of oxidized LDL--a putative triggering molecule in the
      atherosclerotic process. Our results point to a novel alternative mechanism of
      action of alpha-tcp.

PMID- 7518839
TI  - The random inactivation of the X chromosome carrying the defective gene
      responsible for X-linked hyper IgM syndrome (X-HIM) in female carriers of HIGM1.
AB  - The molecular origin of X-linked hyper IgM syndrome has recently been identified
      as a defect in the ligand of CD40, gp39, a protein expressed on the surface of
      activated T cells. The availability of detailed pedigrees for three families with
      affected males allowed assessment of the random or nonrandom nature of the
      inactivation of the defective X chromosome as well as a determination of the
      origin of the mutation. X chromosome inactivation was studied because of the
      relevance to the ability to detect carriers of HIGM1 and the potential for
      phenotypic effect in the carriers. Using immunostaining, PCR, and DNA sequencing,
      we found that the defective gene for gp39 is not selectively inactivated. Even in
      the presence of extremely skewed inactivation, normal levels of serum Ig were
      found. In carriers in which the defective gene is predominantly expressed,
      staining alone revealed the carrier status reliably while cloning and sequencing
      of the cDNA was necessary when the normal gene was predominantly expressed.
      Unlike some other X-linked defects where extreme Lyonization may lead to disease,
      a small population of cells expressing the wild-type gp39 is sufficient to
      maintain normal humoral immunity and prevent the clinical symptoms of X-HIM.

PMID- 7518840
TI  - Basic fibroblast growth factor improves myocardial function in chronically
      ischemic porcine hearts.
AB  - The effect of basic fibroblast growth factor (bFGF) administration on regional
      myocardial function and blood flow in chronically ischemic hearts was studied in
      26 pigs instrumented with proximal circumflex coronary artery (LCX) ameroid
      constrictors. In 13 animals bFGF was administered extraluminally to the proximal
      left anterior descending (LAD) and LCX arteries with heparin-alginate beads and
      13 other animal served as controls. bFGF-treated pigs showed a fourfold reduction
      in left ventricular infarct size compared to untreated controls (infarct size:
      1.2 +/- 0.4% vs. 5.1 +/- 1.3% of LV mass, mean +/- SEM, P < 0.05). Percent
      fractional shortening (% FS) in the LCX area at rest was reduced compared with
      the LAD region in both bFGF and control pigs. However, there was better recovery
      in the LCX area after rapid pacing in bFGF-treated pigs (% FSLCX/% FSLAD, 22.9 +/
      7.3%-->30.5 +/- 8.5%, P < 0.05 vs. prepacing) than in controls (16.0 +/- 7.8%-
      >14.3 +/- 7.0%, P = NS). Furthermore, LV end-diastolic pressure rise with rapid
      pacing was less in bFGF-treated than control pigs (pre-pacing; pacing; post
      pacing, 10 +/- 1; 17 +/- 3; 11 +/- 1* mmHg vs 10 +/- 1; 24 +/- 4; 15 +/- 1 mmHg,
      *P < 0.05 vs. control). Coronary blood flow in the LCX territory (normalized for
      LAD flow) was also better during pacing in bFGF-treated pigs than in controls.
      Thus, periadventitial administration of bFGF in a gradual coronary occlusion
      model in pigs results in improvement of coronary flow and reduction in infarct
      size in the compromised territory as well as in prevention of pacing-induced
      hemodynamic deterioration.

PMID- 7518841
TI  - The necrotic venom of the brown recluse spider induces dysregulated endothelial
      cell-dependent neutrophil activation. Differential induction of GM-CSF, IL-8, and
      E-selectin expression.
AB  - Brown recluse spider (Loxosceles reclusa) venom induces severe dermonecrotic
      lesions. The mechanism for this is unknown but presents an interesting paradox:
      necrosis is completely dependent on the victim's neutrophils, yet neutrophils are
      not activated by the venom. We show Loxosceles venom is a potent, but disjointed,
      endothelial cell agonist. It weakly induced E-selectin expression, but not
      intercellular adhesion molecule-1 or IL-6 expression, yet significantly
      stimulated release of IL-8 and large amounts of GM-CSF by 4 h. In contrast, TNF
      strongly induced all of these, except for GM-CSF. PMN bound to E-selectin on
      venom-activated endothelial cells, apparently via counterreceptors different from
      those that bind E-selectin on TNF alpha-activated monolayers. Notably, PMN bound
      venom-activated monolayers only at intercellular junctions, did not polarize, and
      completely failed to migrate beneath the monolayer. Despite this, bound PMN
      demonstrated increased intracellular Ca2+ levels and secreted primary and
      secondary granule markers. The latter event was suppressed by sulfones used to
      treat envenomation. We have defined a new endothelial cell agonist, Loxosceles
      venom, that differentially stimulates the inflammatory response of endothelial
      cells. This, in turn, leads to a dysregulated PMN response where adhesion and
      degranulation are completely dissociated from shape change and transmigration.

PMID- 7518842
TI  - Induction of myocardial nitric oxide synthase by cardiac allograft rejection.
AB  - Cardiac transplantation, effective therapy for end-stage heart failure, is
      frequently complicated by allograft rejection, the mechanisms of which remain
      incompletely understood. Nitric oxide (NO), a vasodilator which is cytotoxic and
      negatively inotropic, can be produced in large amounts by an inducible NO
      synthase (iNOS) in response to cytokines. To investigate whether iNOS is induced
      during cardiac allograft rejection, hearts from Lewis or Wistar-Furth rats were
      transplanted into Lewis recipients. At day 5, allogeneic grafts manifested
      reduced contractility and histologic evidence of rejection (inflammatory
      infiltrate, edema, necrosis of myocytes). The mRNA for iNOS and iNOS protein were
      detected in ventricular homogenates and in isolated cardiac myocytes from
      rejecting allogeneic grafts but not in tissue and myocytes from syngeneic control
      grafts. Immunocytochemistry showed increased iNOS staining in infiltrating
      macrophages and in microvascular endothelial cells and cardiac muscle fibers and
      also in isolated purified cardiac myocytes from the rejecting allografts. Using a
      myocardial cytosolic iNOS preparation, nitrite formation from L-arginine and [3H]
      citrulline formation from [3H]L-arginine were increased significantly in the
      rejecting allogeneic grafts (P < 0.01). Myocardial cyclic GMP was also increased
      significantly (P < 0.05). The data indicate myocardial iNOS mRNA, protein and
      enzyme activity are induced in infiltrating macrophages and cardiac myocytes of
      the rejecting allogeneic grafts. Synthesis of NO by iNOS may contribute to
      myocyte necrosis and ventricular failure during cardiac allograft rejection.

PMID- 7518843
TI  - Repression of Fanconi anemia gene (FACC) expression inhibits growth of
      hematopoietic progenitor cells.
AB  - Bone marrow failure is a consistent feature of Fanconi anemia (FA) but it is not
      known whether the bone marrow failure is a direct and specific result of the
      inherited mutation or a consequence of accumulated stem cell losses resulting
      from nonspecific DNA damage. We tested the hypothesis that the protein encoded by
      the FA group C complementing gene (FACC) plays a regulatory role in
      hematopoiesis. We exposed normal human lymphocytes, bone marrow cells,
      endothelial cells, and fibroblasts to an antisense oligodeoxynucleotide (ODN)
      complementary to bases -4 to +14 of FACC mRNA. The mitomycin C assay demonstrated
      that the antisense ODN, but not missense or sense ODNs, repressed FACC gene
      expression in lymphocytes. Treatment with the antisense ODN substantially
      reduced, in a sequence-specific fashion, cytoplasmic levels of FACC mRNA in bone
      marrow cells and lymphocytes. Escalating doses of antisense ODN increasingly
      inhibited clonal growth of erythroid and granulocyte-macrophage progenitor cells
      but did not inhibit growth of fibroblasts or endothelial cells. The antisense ODN
      did not inhibit growth factor gene expression by low density bone marrow cells or
      marrow-derived fibroblasts. We conclude that, while the FACC gene product plays a
      role in defining cellular tolerance to cross-linking agents, it also functions to
      regulate growth, differentiation, and/or survival of normal hematopoietic
      progenitor cells.

PMID- 7518844
TI  - Shear stress selectively upregulates intercellular adhesion molecule-1 expression
      in cultured human vascular endothelial cells.
AB  - Hemodynamic forces induce various functional changes in vascular endothelium,
      many of which reflect alterations in gene expression. We have recently identified
      a cis-acting transcriptional regulatory element, the shear stress response
      element (SSRE), present in the promoters of several genes, that may represent a
      common pathway by which biomechanical forces influence gene expression. In this
      study, we have examined the effect of shear stress on endothelial expression of
      three adhesion molecules: intercellular adhesion molecule-1 (ICAM-1), which
      contains the SSRE in its promoter, and E-selectin (ELAM-1) and vascular cell
      adhesion molecule-1 (VCAM-1), both of which lack the SSRE. Cultured human
      umbilical vein endothelial cells, subjected to a physiologically relevant range
      of laminar shear stresses (2.5-46 dyn/cm2) in a cone and plate apparatus for up
      to 48 h, showed time-dependent but force-independent increases in surface
      immunoreactive ICAM-1. Upregulated ICAM-1 expression was correlated with
      increased adhesion of the JY lymphocytic cell line. Northern blot analysis
      revealed increased ICAM-1 transcript as early as 2 h after the onset of shear
      stress. In contrast, E-selectin and vascular cell adhesion molecule-1 transcript
      and cell-surface protein were not upregulated at any time point examined. This
      selective regulation of adhesion molecule expression in vascular endothelium
      suggests that biomechanical forces, in addition to humoral stimuli, may
      contribute to differential endothelial gene expression and thus represent
      pathophysiologically relevant stimuli in inflammation and atherosclerosis.

PMID- 7518845
TI  - Exaggerated and persistent cutaneous delayed-type hypersensitivity in transgenic
      mice whose epidermal keratinocytes constitutively express B7-1 antigen.
AB  - Since mouse keratinocytes are tolerogenic antigen presenting cells for T cell
      activation, the expression of second signal molecules such as B7-1 was targeted
      to epidermal keratinocytes (KC) in vivo in transgenic mice. The expression vector
      used to create transgenic mice consisted of a keratin 14 promoter fused 5' to the
      full length open reading frame of the cDNA encoding mouse B7-1 (between 10 and 30
      copies of the transgene per genome). Expression of B7-1 cell surface protein was
      assessed by in situ immunostaining of cryostat sections of tail skin with CTLA
      4/Ig fusion protein, revealing high levels of cell surface expression of B7 by
      all epidermal KC of transgenic mice, and a lack of such expression in
      nontransgenic animals. The skin of such transgenic mice (derived from three
      different founder mice) was grossly and histologically normal, with normal
      numbers of Langerhans cells and dendritic epidermal T cells. Immunologic
      challenge of transgenic mice with epicutaneous haptens such as fluorescein
      isothiocyanate revealed enhanced and persistent delayed-type hypersensitivity
      responses, with an altered kinetics of resolution when compared with
      nontransgenic controls. These data indicate that in normal, nontransgenic mice,
      tolerogenic antigen presentation by KC plays an important physiologic role in
      damping T cell-mediated inflammation in the skin by competing with professional
      APC for TCR occupancy in antigen specific T-lymphocytes that migrate into the
      epidermis. This also implies that altered regulation of B7-1 gene expression by
      epidermal cells may account for skin "hyperresponsiveness" encountered in some
      chronic dermatologic disorders.

PMID- 7518847
TI  - Cutaneous vasculitis associated with granulocyte colony-stimulating factor.
AB  - BACKGROUND: Several cases of cutaneous vasculitis have been reported in patients
      treated with granulocyte colony-stimulating factor (G-CSF). OBJECTIVE: The
      purpose of this study was to determine the prevalence of cutaneous vasculitis in
      patients receiving G-CSF therapy, causal relation to the drug, and possible
      pathomechanisms. METHODS: Review of the literature, retrieval of cases from the
      safety database of the manufacturer of G-CSF, and global assessment of the causal
      relation of the drug to adverse drug reactions were done. RESULTS: Eighteen cases
      of cutaneous vasculitis were found, of which only three have been published. A
      skin biopsy was done in 12 and showed leukocytoclastic vasculitis. Although
      cutaneous vasculitis was rare in patients treated for neutropenia associated with
      malignant disease and chemotherapy, it occurred in 6% of the patients with
      chronic benign neutropenias. Cutaneous vasculitis usually followed the increase
      of absolute neutrophil count (ANC) and subsided after the decrease of ANC. There
      was no recurrence if ANC was kept below 800/mm3. The course of G-CSF was
      completed in most patients. CONCLUSION: Cutaneous vasculitis should be recognized
      as an adverse reaction to G-CSF with low morbidity. It can be managed by
      reduction of dose or discontinuation of G-CSF therapy and use of topical
      steroids.

PMID- 7518846
TI  - Afferents to the nucleus reticularis parvicellularis of the cat medulla
      oblongata: a tract-tracing study with cholera toxin B subunit.
AB  - The aim of this study was to examine anatomical evidence in cats of whether the
      nucleus reticularis parvicellularis (Pc) is part of the circuit responsible for
      the inhibition of brainstem motoneurons during paradoxical sleep. For this
      purpose, we made iontophoretic injections of the retrograde and anterograde
      tracer cholera toxin B subunit (CTb) in the Pc. After CTb injections in the Pc, a
      large number of retrogradely labeled neurons were seen in the central nucleus of
      the amygdala, the lateral part of the bed nucleus of the stria terminalis, the
      posterior hypothalamic areas, the mesencephalic reticular formation, the nucleus
      locus subcoeruleus, the nucleus pontis caudalis, other portions of the Pc, the
      nucleus reticularis dorsalis, the trigeminal sensory complex, and the nucleus of
      the solitary tract. We further found that the Pc receives 1) serotoninergic
      afferents from the raphe dorsalis, magnus, and obscurus nuclei; 2) noradrenergic
      inputs from the dorsolateral pontine tegmentum; 3) cholinergic afferents from the
      lateral medullary reticular formation; 4) substance P-like afferents from the
      central nucleus of the amygdala, bed nucleus of the stria terminalis,
      periaqueductal gray, and nucleus of the solitary tract; and 5) methionine
      enkephalin-like projections from the periaqueductal gray, the nucleus of the
      solitary tract, the lateral pontine and medullary reticular formation, and the
      spinal trigeminal nucleus. We further found that the Pc do not receive afferents
      from brainstem structures responsible for muscle atonia, such as the ventromedial
      medulla and the dorsomedial pontine tegmentum, and therefore may not be part of
      the circuit inhibiting the brainstem motoneurons during paradoxical sleep.

PMID- 7518848
TI  - Immunohistochemical detection of keratin with the monoclonal antibody MNF116 is
      useful in the diagnosis of epidermolysis bullosa simplex.
AB  - Epidermolysis bullosa simplex (EBS) is an uncommon genetic skin disease
      characterized by fragility of the basal keratinocytes and propensity to develop
      blisters. While a panel of antibodies against type IV collagen, laminin, and
      bullous pemphigoid antigen has been used to identify cases of EBS in frozen
      sections, we have found that a monoclonal antibody detecting cytokeratin in basal
      keratinocytes is useful in paraffin sections. Formalin-fixed, paraffin-embedded
      tissues from 12 patients with EBS were studied with the following monoclonal
      antibodies: MNF116 (DAKO, Carpinteria, CA), CAM 5.2 (Becton Dickinson, San Jose,
      CA), and AE1-AE3 mixture (Boehringer Mannheim Corp, Indianapolis, IN).
      Histologically, all the cases had focal vacuolization of the basal cell layer,
      with areas of dermal-epidermal separation. MNF116 was strongly positive in the
      basal keratinocytes, including the vacuolated ones, and demonstrated the presence
      of fragments of keratinocytes attached to the floor of the blister. CAM 5.2
      stained sweat ducts only. AE1-AE3 was weakly positive in the basal cells, and
      almost completely negative on the fragmented basal cell keratinocytes. We
      consider that the immunostain with MNF116 in tissues fixed routinely in formalin
      and embedded in paraffin is helpful for the direct demonstration of the level of
      splitting in EBS.

PMID- 7518849
TI  - Coexpression of cytokeratin and vimentin intermediate filaments in benign and
      malignant sweat gland tumors.
AB  - The coexpression of cytokeratin and vimentin intermediate filaments has been
      immunohistochemically evaluated in 124 benign and malignant sweat gland tumors of
      various types in comparison to normal sweat glands. In addition, all neoplasms
      have been stained by an antibody to alpha-smooth muscle actin. Epithelial cells
      reacted with the pan-cytokeratin antibody lu-5. In normal sweat glands, vimentin
      immunoreactivity was restricted to myoepithelial cells and to some cells of the
      coiled duct. In benign sweat gland tumors (n = 88), coexpression of vimentin and
      alpha-smooth muscle actin was frequently found in basal cells of neoplasms
      considered to differentiate towards the secretory coil of the eccrine or apocrine
      gland. These included eccrine spiradenoma, apocrine cystadenoma, hidradenoma
      papilliferum, syringocystadenoma papilliferum, and cylindroma. Thus, in these
      tumors, vimentin-reactive cells corresponded to myoepithelial cells. Vimentin
      positive cells were also found in 14 of 36 sweat gland carcinomas, including 1
      case of sclerosing sweat duct carcinoma, 1 case of porocarcinoma, 4 cases of
      eccrine adenocarcinoma, 1 case of mucinous eccrine carcinoma, and 5 cases of
      apocrine adenocarcinoma. Co-expression of vimentin and alpha-smooth muscle actin
      was observed in some cells of eccrine and apocrine adenocarcinomas. Therefore, in
      these neoplasms, some vimentin-positive cells appear to represent myoepithelial
      cells. In contrast, vimentin-positive cells in all other malignant tumors did not
      express alpha-smooth muscle actin. Our results indicate that coexpression of
      cytokeratin and vimentin may be frequently found in a variety of benign and
      malignant sweat gland tumors. In the majority of these neoplasms, vimentin
      positive cells correspond to myoepithelial cells. Because vimentin is not
      specific for myoepithelial cells, additional stains for alpha-smooth muscle actin
      should be performed to prove the myoepithelial nature of vimentin-positive cells.

PMID- 7518850
TI  - CD34-positive spindle cells in nerves.

PMID- 7518851
TI  - Detection of phosphotyrosine in glutaraldehyde-crosslinked and alkali-treated
      phosphoproteins following their partial acid hydrolysis in gels.
AB  - Soluble fractions and particulate extracts from human prostate, and extracts from
      rat-liver membranes were used as a source of kinases to phosphorylate endogenous
      proteins in the presence of gamma- 32P-labeled ATP. Histone was also added as a
      substrate in order to compare the direct partial acid hydrolysis of
      phosphoproteins in gels to an indirect procedure involving partial acid
      hydrolysis after extraction in sodium dodecyl sulfate followed by precipitation
      with acetone. These procedures led to recoveries of 32P-labeled material of 90%
      and 40%, respectively, with a similar proportion of radiolabeled phosphoamino
      acids. Several 32P-labeled phosphoproteins separated in gels were therefore
      directly HCl-hydrolyzed and their phosphoamino acids were quantitated either
      prior to, or after glutaraldehyde crosslinking, with and without alkali
      treatment. By preventing protein losses occurring in hot alkali, glutaraldehyde
      crosslinking increased by an average factor of 6.5 the 32P-labeled material
      available for phosphoamino-acid analyses. For eight phosphoproteins analyzed, the
      overall effect of combined glutaraldehyde and alkali treatments was a relative
      decrease in phosphoserine (up to 8-fold), with concomitant relative increases in
      phosphotyrosine and phosphothreonine (up to 62- and 6-fold, respectively). This
      method will especially be useful for the detection of pTyr, a less abundant
      phosphoamino acid, in proteins which suffer from poor transfer efficiency in
      Western blot, are weakly antigenic towards anti-phosphotyrosine antibodies, can
      hardly be extracted from a gel and for identification of protein tyrosine kinases
      renatured in gels.

PMID- 7518852
TI  - A dyed substrate for the assay of endo-1,4-beta-glucanases.
AB  - A new dyed substrate was prepared for the rapid determination of endo-1,4-beta
      glucanases. Carboxymethylcellulose was coupled with Ruthenium red to obtain a
      violet powder, which was stable enough to allow for reproducible assays. The
      spontaneous reaction is based on ionic interactions between the negatively
      charged carboxymethylcellulose and the complex cation of the dye. The enzymic
      assay is based on spectrophotometric measurement at 535 nm of the enzyme-released
      dyed fragments with low-molecular-weight filterable through a 0.22 microns
      filter. The release of coloured fragments from this dyed substrate was
      proportional to its solubilization. The absorbance was directly proportional to
      the enzyme amount in the range 0.5-5.5 mU enzyme (A535 = 0.1-0.95). This enzymic
      assay is advantageous for both rapid time of analysis and sensitivity.

PMID- 7518853
TI  - [Primary choriocarcinoma of the cervix].
AB  - We report a case of primary choriocarcinoma of the cervix in which the patient
      died 9 months later. The treatment consisted to administer 5 cycles of
      chemotherapy pre-operatively and a colpohysterectomy. The pathogeny is a cervical
      migration of trophoblastics cells after a normal or molar pregnancy which
      degenerate to choriocarcinoma.

PMID- 7518854
TI  - Inhibition of proliferation of human melanocytes by a KIT antisense
      oligodeoxynucleotide: implications for human piebaldism and mouse dominant white
      spotting (W).
AB  - KIT constitutes the cell surface transmembrane receptor protein tyrosine kinase
      for a growth factor variously termed steel factor (SLF), stem cell factor, mast
      cell growth factor, or Kit ligand. Inherited mutations of the KIT gene result in
      piebaldism in humans and dominant white spotting (W) in mice. Patches of
      hypopigmented skin and hair in these disorders represent regions lacking in
      melanocytes, the result of defective melanoblast differentiation, migration,
      proliferation, or survival during embryonic development. Here we show that
      incubation of normal human melanocytes with a KIT antisense oligodeoxynucleotide
      greatly inhibits cell proliferation in culture, whereas incubation with a KIT
      sense oligodeoxynucleotide has no effect. The KIT oligodeoxynucleotides also had
      little or no effect on cell survival.

PMID- 7518855
TI  - Cultured murine dermal cells can function like thymic nurse cells.
AB  - We have established a dermal fibroblast-like stromal cell line, DFB-1, and a
      clone, 12E2, from epidermal sheets prepared from the skin of BALB/c mouse ears by
      trypsin digestion. They were suggested to be fibroblasts or myofibroblasts, as 1)
      they were polygonal or spindle-shaped under the phase-contrast microscope, 2)
      they did not possess any tonofilaments or desmosomes, and 3) they did not express
      any marker for bone marrow-derived cells or macrophages. Interestingly, these
      cells showed a unique phenomenon of "pseudo-emperiporesis," which was first
      recognized in the interaction between thymic nurse cells and thymocytes. Namely,
      two T-cell clones and one T-cell hybridoma migrated beneath the cytoplasmic
      projections of the fibroblast-like cutaneous stromal cells in culture.
      Furthermore, secretion of interleukin 7 by these cells was confirmed by bioassay
      using an IL-7-dependent cell line and by inhibition with anti-interleukin 7
      antibody, and the expression of interleukin 7 mRNA was also demonstrated in these
      cells by a combination of reverse-transcriptase polymerase chain reaction and
      Southern blot analysis. These data strongly suggest the presence of unique
      stromal cells even in the skin, probably at the upper dermis, which can function
      like the nurse cells in the thymus. These stromal cells may play a crucial role
      in cutaneous immunophysiology.

PMID- 7518856
TI  - Immunohistochemical demonstration of keratin 19 expression in isolated human hair
      follicles.
AB  - We examined keratins 19 and 8 in extracted human hair follicles using monoclonal
      antibodies Ks19.1 and CAM5.2, respectively. Ks19.1 reactivity was found in the
      bulge and infundibulum. Ks19.1(+) cells were dense in the bulge of vellus and
      intermediate hair follicles. The intact bulge of terminal hair could not be
      extracted, but the presence of Ks19.1(+) cells was confirmed in transverse
      sections. Infundibular Ks19.1(+) cells exhibited a dense network pattern of
      staining in terminal hair follicle, but only a few cells were labeled in vellus
      and intermediate hair follicles. CAM5.2(+) cells, i.e., Merkel cells, were found
      in the same locations as Ks19.1(+) cells but were less dense. These patterns of
      distribution and staining density were not influenced by different phases of hair
      cycle. Sequential staining of Ks19.1 and CAM5.2 in the same hair follicle
      demonstrated that the same cells could be reactive for both. However, considering
      the large number of Ks19.1(+) cells and rather small number of CAM5.2 in the same
      locations, it was assumed that only a subset of Ks19.1(+) cells are Merkel cells.
      It was postulated that the bulge area of human adult hair follicles houses
      embryonic pluripotential cells characterized by stem cells and post-stem cells
      and that the Merkel cells in the bulge area arise from these immature cells and
      may play a role in the maintenance and stimulation of this group of immature
      cells.

PMID- 7518857
TI  - Effects of ascorbic acid on proliferation and collagen synthesis in relation to
      the donor age of human dermal fibroblasts.
AB  - Several events are associated with cellular aging: alterations in the
      extracellular matrix, loss of the cell's proliferative capacity, and decreased
      responsiveness to growth factors. In skin, a major component of the extracellular
      matrix is collagen; an important regulator of collagen synthesis is ascorbic
      acid, which may also have growth factor-like properties. To investigate the
      relationship of the extracellular matrix and proliferative capacity to aging, we
      examined the effects of ascorbic acid on cell proliferation and collagen
      expression in dermal fibroblasts from donors of two age classes, newborn (3-8 d
      old) and elderly (78-93 years old). In the absence of ascorbic acid (control)
      proliferative capacities were inversely related to age; newborn cell lines
      proliferated faster and reached greater densities than elderly cell lines.
      However, in the presence of ascorbic acid both newborn and elderly cells
      proliferated at a faster rate and reached higher densities than controls. To
      determine whether there are age-related differences in extracellular matrix
      production and ascorbic acid responsiveness we examined and found that collagen
      biosynthesis (collagenase-digestible protein) was inversely related to age, but
      the stimulation by ascorbic acid appeared age independent. The increase in
      collagen synthesis was reflected by coordinate increases in steady-state pro
      alpha 1(I) and pro alpha 1(III) collagen mRNAs, suggesting a pretranslational
      mechanism. Ascorbic acid appears capable of overcoming the reduced proliferative
      capacity of elderly dermal fibroblasts, as well as increasing collagen synthesis
      in elderly cells by similar degrees as in newborn cells even though basal levels
      of collagen synthesis are age dependent.

PMID- 7518858
TI  - Topography of mammalian connexins in human skin.
AB  - We have explored the expression of gap junction proteins in normal human skin by
      immunostaining cryostat sections (indirect immunofluorescence) or lyophilized
      epidermis (Western blotting) with antibodies against four mammalian connexins
      Cx26, Cx32, Cx40, Cx43; and by hybridizing total epidermal RNA (Northern
      blotting) with cRNA probes for Cx26, Cx32, and Cx43. We found that epidermal
      keratinocytes express Cx43 but not Cx26, Cx32, or Cx40. This expression was
      minimal in the basal layer, much higher in the spinous layer, reduced in the
      granular layer, and absent in the stratum corneum. Immunostaining for Cx43 was
      also observed in sebaceous glands, hairs, and eccrine sweat ducts. The two latter
      epidermal adnexae were also markedly labeled by antibodies against Cx26, a gap
      junction protein that was undetectable by immunofluorescence in interfollicular
      keratinocytes. Immunoblots of polyacrylamide gel electrophoresis-separated
      epidermal proteins and hybridization of epidermal RNA confirmed the presence of
      Cx43 in epidermis. These observations indicate that 1) Cx43 and Cx26 are
      components of human keratinocyte gap junctions; 2) these two proteins are
      differentially expressed in the interfollicular epidermis and the skin adnexae;
      3) in interfollicular epidermis, Cx43 is a predominant gap junction protein,
      mostly expressed by the differentiating spinous cells; 4) Cx43 distribution is in
      accordance with the extensive dye coupling previously observed in this epidermal
      compartment.

PMID- 7518859
TI  - Clinical modulation of multidrug resistance in multiple myeloma: effect of
      cyclosporine on resistant tumor cells.
AB  - PURPOSE: In multiple myeloma (MM) refractory to doxorubicin (DXR) and/or
      vincristine (VCR), myeloma cells frequently express the multidrug resistance
      (MDR) phenotype, associated with overexpression of P-glycoprotein (Pgp), which
      acts as a drug efflux pump. Recently, studies have shown that clinical resistance
      can be modulated by drug resistance modifiers. The present study was performed to
      investigate if MDR modulation in vivo is caused by a direct effect of
      cyclosporine (CSA) on resistant myeloma plasma cells (PC). PATIENTS AND METHODS:
      Eight patients with VAD-refractory MM were treated with DXR, VCR, and
      dexamethasone (VAD) plus CSA. Pgp expression in PC was determined by flow
      cytometry/immunocytochemistry before and after clinical treatment. Functional Pgp
      expression was determined by the effect of CSA on the intracellular accumulation
      of DXR and VCR. RESULTS: Five of eight patients responded to VAD/CSA. The
      percentage of Pgp-positive (Pgp+) PC was 30% to 100% (median, 90%) before
      treatment and 4 to 90% (median, 40%) after treatment. CD56+/- or CD38+/- PC had
      identical Pgp expression. CSA, as well as SDZ PSC 833, but not dexamethasone,
      increased pretreatment intracellular accumulation of DXR and VCR in Pgp+ PC in
      three of four and six of six patients, respectively. After clinical treatment, in
      vitro drug accumulation in residual Pgp-negative (Pgp-) PC of four of four
      responding patients was not further modulated by CSA or SDZ PSC 833. At later
      relapse, PC of two of four patients remained Pgp-. CONCLUSION: These data
      indicate that Pgp overexpression is functional in refractory myeloma and that
      clinical modulation of MDR by CSA is mediated through an inhibition of Pgp
      associated drug efflux. Pgp-expressing PC can be eliminated by clinical treatment
      with VAD/CSA.

PMID- 7518862
TI  - Defining a mission statement and setting goals.

PMID- 7518861
TI  - Development of a simplified single-apheresis approach for peripheral-blood
      progenitor-cell transplantation in previously treated patients with lymphoma.
AB  - PURPOSE: The aims of this study were to develop a simplified, safe, and cost
      effective peripheral-blood progenitor-cell (PBPC) mobilization protocol. PATIENTS
      AND METHODS: Twenty-six patients with relapsed or resistant lymphomas were
      entered onto a sequential cohort study in which schedules of various granulocyte
      colony-stimulating factor (G-CSF) were administered after cyclophosphamide 1.5
      g/m2. Hematologic recovery after high-dose carmustine (BCNU) etoposide,
      cytarabine, and melphalan (BEAM) chemotherapy was compared with that of 46
      patients who received autologous bone marrow transplantation (ABMT) without
      growth factors and 28 patients who received ABMT followed by G-CSF. RESULTS: When
      G-CSF (10 micrograms/kg/d) was administered from the day after the
      cyclophosphamide, neutropenia developed on day 8 followed by an abrupt increase
      in the WBC count. The optimal time for PBPC harvesting was the day on which the
      postnadir WBC count was greater than 8.0 x 10(9)/L, as shown by CD34+ cell counts
      and granulocytic-macrophage colony-forming cell (GM-CFC) assays. The
      reproducibility of the response was such that routine monitoring of CD34+ cell
      counts and GM-CFC was not necessary. A single leukapheresis on this day was
      adequate for prompt hematologic engraftment, and posttransplant G-CSF made little
      further impact on the rapid recovery. Compared with both control groups, the use
      of PBPC led to more rapid neutrophil recovery, markedly accelerated platelet
      recovery, less use of antimicrobial agents and parenteral nutrition, and more
      than 10 days earlier discharge from hospital. All of these differences were
      highly significant (P < .01). CONCLUSION: A simplified mobilization protocol is
      described that requires only one apheresis to achieve rapid hematologic
      engraftment.

PMID- 7518860
TI  - Sequential high-dose therapy with peripheral-blood progenitor-cell support in low
      grade non-Hodgkin's lymphoma.
AB  - PURPOSE: To evaluate the feasibility of a sequential high-dose therapy with
      peripheral-blood progenitor-cell (PBPC) support in patients with follicular
      lymphoma. PATIENTS AND METHODS: Since July 1991, we have included 30 patients (17
      men and 13 women) with a median age of 41 years (range, 26 to 55) in the study.
      At the time of study entry, 17 patients were in first and six in second or higher
      remission. Another six patients had relapse of disease and one had tumor
      progression. PBPC were collected during filgrastim-supported leukocyte recovery
      following high-dose cytarabine (ara-C)/mitoxantrone (HAM). RESULTS: A median of
      two leukaphereses (range, one to seven) resulted in a median of 5.7 x 10(6) CD34+
      cells/kg (range, 2.9 to 23.7 x 10(6). A distinct population of B-lymphoid
      progenitors (CD34+/CD19+) was not detectable in the autografts, and the content
      of CD19+ B cells was remarkably low, comprising a median of 0.07% of the
      mononuclear cells. Using the polymerase chain reaction (PCR) assay for the major
      breakpoint regions (MBR) of the bcl-2/immunoglobulin H (IgH) translocation, 22
      patients had autografts positive for the t(14;18) translocation, whereas seven
      patients had PCR-negative transplants. The autograft of one patient could not be
      assessed. Following myeloablative therapy, hematologic recovery was rapid without
      cytokine support. The median times to reach a platelet count > or = 20 x 10(9)/L
      and neutrophil count > or = 0.5 x 10(9)/L were 11 and 13 days, respectively.
      Nonhematologic toxicity was moderate. Twenty-nine patients were alive in
      remission after a median follow-up duration of 6 months (range, 1 to 18). Of 22
      patients autografted with t(14;18)-positive harvests, 11 had PCR-detectable cells
      in bone marrow and/or peripheral blood as long as 16 months posttransplantation.
      In contrast, six patients became PCR-negative between 3 and 16 months after
      reinfusion. Follow-up examinations with PCR data for the remaining five patients
      are not yet available. CONCLUSION: Conversion to PCR negativity in patients
      autografted with PCR-positive harvests suggests that the myeloablative regimen is
      effective and that any reinfused t(14;18)-positive cells may not be sustained.
      Because conventional chemotherapy provides no cure, we believe that high-dose
      therapy including total-body irradiation (TBI) should be explored in these
      particularly radiosensitive lymphomas.

PMID- 7518863
TI  - Serving, sensing and satisfying.

PMID- 7518864
TI  - When insurance ends: a fee-for-service practice model.

PMID- 7518865
TI  - Planning transitions: rehearsing the future.

PMID- 7518866
TI  - The insurance game.

PMID- 7518867
TI  - Drugs commonly used by the elderly: a review for dental practice.
AB  - Of all medications consumed in the U.S., the percentage used by the elderly is
      greater than can be justified by their numbers. Many medications have adverse
      effects. This paper reviews the 50 medications most used by the elderly and
      discusses adverse reactions which may present in the oral cavity or which have
      systemic effects with a potential impact on dental care. Composite tables
      summarizing the adverse reactions of interest to the dental practitioner are
      included for easy reference.

PMID- 7518868
TI  - Fluorides for the elderly.
AB  - With the current decline in the rate of dental caries among school children, the
      elderly now have the higher rate of decayed coronal surfaces in addition to being
      susceptible to root caries. The most effective strategy that the profession can
      take is twofold: thoroughly assess the level of caries risk of the elderly
      individual, and institute recognized measures of fluoride therapy commensurate
      with the defined risk. This review article describes risk indicators
      characteristic of the elderly patient and offers specific fluoride regimens for
      low, moderate and high risk subjects.

PMID- 7518869
TI  - Restorative treatment for geriatric root caries.
AB  - The restorative management of root caries poses many challenges to the clinician.
      The clinical features of root caries and current restorative techniques using new
      adhesive materials are discussed.

PMID- 7518870
TI  - Salivary gland hypofunction in elderly patients.
AB  - Elderly dental patients often complain of mouth dryness. This complaint is most
      often caused by xerogenic medications or, less often, by systemic diseases. Aging
      per se has no significant clinical impact on salivary gland output. Salivary
      gland hypofunction, whether caused by medications or systemic disorders, have a
      strong negative impact on intraoral tissues, with a significant reduction in the
      quality of life.

PMID- 7518872
TI  - Post and core conflict.

PMID- 7518873
TI  - Biochemical parameters of epidermal aging in the hairless mouse and the
      relationship to UV-carcinogenesis.
AB  - Epidemiological studies suggest that the incidence of cancer increases with age
      in both human and animal populations and that declining physiologic condition
      associated with aging might be responsible. Experimentally, the reverse has been
      most often observed, that is, older animals appear less susceptible to the
      induction of UV-carcinogenesis. Thus, we examined several biochemical parameters
      of epidermal macromolecular synthesis in hairless mice in an effort to gain
      insight into the role these processes play in physiological aging and their
      relationship to carcinogenesis. SKh-Hr-1 hairless mice were randomized into two
      groups (UV-irradiated and non-irradiated controls) and were two months of age at
      the start of irradiation and biochemical analyses. The UV group received 0.028
      sunburn units (SBUs) daily (5 days wk-1) for 16 months from 40 watt BZS-WLG
      lamps. Stratum corneum turnover rates (SCR), cell label index (CLI), protein, DNA
      and RNA synthesis, and ornithine decarboxylase (ODC) induction were determined at
      monthly intervals over a period of two years. There were no age-related
      tendencies observed in SCR. CLI increased with age. Chronic, low-dose UV had no
      effect upon either of these parameters. Epidermal capacity for DNA and protein
      synthesis increased with age from 2 months to 12-15 months at which time both
      parameters peaked and then began to decline. UV significantly reduced (P < 0.04)
      the magnitude of DNA synthetic capacity at peak periods of synthesis but had no
      effect upon protein synthesis. RNA synthetic rates declined with age, reaching
      their lowest levels at 24 months. Further, a significant reduction (P < 0.001) in
      ODC inducibility occurred with advancing age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7518871
TI  - Osteoporosis and periodontal disease: a review.
AB  - A review of the literature on the relationship between osteoporosis and
      periodontal disease is presented. Osteoporosis, a metabolic disease, and
      periodontal disease, which is infectious, are both major health problems with
      multifactorial etiologies. There is histologic and radiographic evidence from
      animals and humans that osteoporosis does affect alveolar bone by decreasing bone
      mass and trabeculation. The literature reviewed in this paper suggests, but does
      not yet provide conclusive evidence for, a direct relationship between
      osteoporosis and periodontal disease.

PMID- 7518874
TI  - [Principle and practice of patch-clamp technique].

PMID- 7518875
TI  - IgG subclass distribution of anti-hCG and anti-diphtheria toxoid antibodies in
      women immunized with a beta-hCG based immunocontraceptive vaccine.
AB  - IgG subclass distribution of antibodies against human chorionic gonadotropin
      (hCG) and diphtheria toxoid (DT) was determined in the sera of women recruited
      into Phase II clinical trials of a beta-hCG based immunocontraceptive vaccine.
      Serum samples from 30 different individuals were analyzed. Anti-hCG antibody
      response was predominantly of IgG1 subclass, with a mean titer of 537.94 +/- 560
      antibody units (AU). The other 3 subclasses showed considerably lower mean levels
      (IgG2, 16.46 +/- 8.33; IgG3, 3.22 +/- 8.48; IgG4, 56.65 +/- 82.60 AU). A good
      correlation was observed between the anti-hCG IgG1 antibody titers (r = 0.57, P <
      0.01) and the bioneutralization capacity of sera. However, bioneutralization
      capacity of the sera from subjects capable of inducing IgG4 response was not
      significantly different from subjects not showing IgG4 antibodies. Similarly, a
      dominant IgG1 response was observed against diphtheria toxoid (DT) which has been
      used as one of the carrier proteins in the vaccine.

PMID- 7518876
TI  - Association of ovarian malignancy with expression of platelet-derived endothelial
      cell growth factor.
AB  - BACKGROUND: At the present time, the pathogenesis of ovarian cancer remains
      poorly understood, with invasive diagnosis and ineffective treatment for women
      with the disease. Despite scientific and medical advances in oncology, the
      overall 5-year survival rate of 30% for ovarian cancer patients has not changed
      in 20 years. An understanding of the angiogenic process as it occurs in ovarian
      cancer would not only increase our knowledge of the pathogenesis of this cancer
      but also might offer novel opportunities for therapeutic intervention. PURPOSE:
      Our aim was to study the expression of messenger RNA (mRNA) coding for four
      putative angiogenic factors in normal ovaries and benign and malignant ovarian
      tumors: platelet-derived endothelial cell growth factor (thymidine
      phosphorylase), vascular endothelial growth factor, basic fibroblast growth
      factor, and transforming growth factor-beta 1. METHODS: Four normal ovaries and
      25 tumors (seven benign, one of borderline malignancy, and 17 malignant) were
      collected from 29 patients during elective oophorectomy. The site of sampling
      (areas of high-velocity blood flow) was directed by transvaginal color Doppler
      imaging performed within 24 hours of the surgery. Increased blood flow within the
      tissues was demonstrated by the presence of color (i.e., the velocity was > 7
      cm/s) and, together with a pulsatile index of less than 1.0, constituted a
      positive scanning result. In scan-positive tissues, the area of maximum blood
      flow was chosen. In scan-negative tissues, a solid area was chosen in complex
      lesions, or the cyst wall was chosen in simple lesions. Ovarian RNA was
      subsequently extracted from areas of high-velocity flow (i.e., tissues with a
      positive scanning result) or from solid areas or septa in tissues with a negative
      scanning result. A ribonuclease protection assay was used to assess the
      expression of mRNA coding for the four angiogenic factors. RESULTS: Two normal
      ovaries (containing a corpus luteum) and one benign and 17 malignant tumors (plus
      the borderline) gave a positive scanning result. There was a significant
      difference between the expression of mRNA for platelet-derived endothelial cell
      growth factor between scan-positive and scan-negative tissues (P < .001) and
      between benign and malignant tumors (P < .001). CONCLUSIONS: Areas of high blood
      velocity in ovarian tumors are associated with increased expression of platelet
      derived endothelial cell growth factor. IMPLICATIONS: Drugs that affect the
      angiogenic activity of platelet-derived endothelial cell growth factor offer a
      potential route for therapeutic intervention.

PMID- 7518877
TI  - The hormonal profile in ectopic pregnancies.
AB  - We prospectively investigated the maternal serum level of beta- human chorionic
      gonadotropin (beta-hCG) progesterone (P), estradiol (E2), human placental
      lactogen (HPL), alfa-fetoprotein (AFP) and cancer antigen 125 (CA 125) during the
      first trimester of normal and abnormal pregnancies. Serum samples were obtained
      from 20 women with normal intra-uterine pregnancy (IUPs). Fifteen whose
      pregnancies were complicated with spontaneous abortion and 31 with surgically and
      pathologically confirmed ectopic pregnancies (EPs). The mean serum levels of beta
      hCG, E2 and P in patients with Eps (9490.55 +/- 3071.2 mIU/ml, 100.1 +/- 22.09
      pg/ml, 4.18 +/- 1.19 ng/ml, respectively) were significantly lower than those
      measured in normal IUPs (73796.8 +/- 15554.7 mIU/ml, 500.15 +/- 98.84 pg/ml, 19.2
      +/- 2.8 ng/ml respectively (p < 0.001) and significantly lower than in patients
      with spontaneous abortion (22524 +/- 6213 mIU/ml, p < 0.05, 339.8 +/- 112.16
      pg/ml, p < 0.01, 10.59 +/- 3.03 ng/ml, p < 0.05 respectively). No significant
      difference was recorded with respect to serum levels of HPL, AFP and CA 125 among
      the groups. We also investigated the diagnostic value of simple E2 and P in
      patients with EPs. We could not identify a discriminatory cutoff value because
      there was a considerable overlap in serum P ans E2 levels between the patients
      with IUPs and EPs. In conclusion, it is not possible to define a cutoff
      discriminatory value of P and E2 that completely separates ectopic from IUPs, but
      the addition of these assays to the workup of a patient with suspected EP may
      facilitate the earlier diagnosis of EP.

PMID- 7518879
TI  - Effect of L-carnitine on the zidovudine-induced destruction of human myotubes.
      Part I: L-carnitine prevents the myotoxicity of AZT in vitro.
AB  - BACKGROUND: Zidovudine (AZT) as used in the treatment of AIDS, causes a
      mitochondrial myopathy characterized by depletion of mitochondrial DNA, enzymatic
      defects in the respiratory chain system, and accumulation of lipid droplets. Most
      of these changes are also seen in normal human myotubes treated with AZT. Because
      L-carnitine plays a major role in the transport of long chain fatty acids across
      the inner mitochondrial membrane and facilitates the beta-oxidation of fatty
      acids, we examined the effect of L-carnitine in preventing the destructive effect
      of AZT on the mitochondria and the myotubes of human muscle in tissue culture.
      EXPERIMENTAL DESIGN: Myotubes, prepared from human muscle biopsies, were exposed
      to various concentrations of AZT for up to 3 weeks. One-third of the flasks were
      treated with AZT alone, another third with AZT plus L-carnitine and another third
      were untreated. The cultures were evaluated with: (a) immunocytochemistry
      counting the number of myotubes stained with antibodies to Leu-19; (b) enzyme
      histochemistry for NADH reaction and oil-red-O stain to assess mitochondrial
      enzymatic activity and lipid droplet accumulation; and (c) electron microscopy
      counting all the organelles within representative sections of the myotubes, at
      x24,000, and calculating the volumetric density of each organelle/unit volume of
      tissue. RESULTS: AZT, at concentrations 250 microM and above, caused depopulation
      of the Leu-19-positive myotubes, destructive changes in the mitochondria
      consisting of swelling, lamellar inclusions and multiple concentric cristae,
      accumulation of lipid droplets, and increase lysosomes. L-Carnitine increased the
      number of Leu-19-positive myotubes from 3.4 +/- 0.6 to 9.4 +/- 1.2, preserved the
      morphology of the mitochondria, increased their volumetric density from 2.5 +/-
      0.4 to 6.0 +/- 0.7, and reduced the volumetric density of the lipid droplets from
      12.2 +/- 4.9 to 1.4 +/- 0.7 and of the lysosomes from 15.6 +/- 3.6 to 3.9 +/- 1.4
      (p < 0.001). CONCLUSIONS: L-Carnitine, used concurrently with AZT, prevents the
      human myotubes from the AZT-associated destruction, preserves the structure and
      volume of mitochondria and prevents the accumulation of lipids. The findings may
      have potential clinical implications in preventing the myotoxicity of AZT in
      patients with AIDS.

PMID- 7518878
TI  - [Complicated colorectal cancer--the procedure and treatment].

PMID- 7518880
TI  - Hair growth induction by substance P.
AB  - BACKGROUND: In vitro, some neuropeptides, including the tachykinin, substance P
      (SP), act as growth factors. The cyclic growth of the richly innervated hair
      follicle offers a model for probing such functions in a complex, developmentally
      regulated tissue interaction system under physiologic conditions. Dissecting the
      role of neuropeptides in this system may also reveal as yet obscure neural
      mechanisms of hair growth control. EXPERIMENTAL DESIGN: The neuropeptide
      releasing neurotoxin, capsaicin was injected intradermally, or SP slow-release
      formulations were implanted subcutaneously in the back skin of C57BL/6 mice with
      all follicles in the resting stage of the hair cycle (telogen) in order to see
      whether this induced hair growth (anagen). In addition, the endogenous SP skin
      concentration and the activity of the main SP-degrading enzyme, neutral
      endopeptidase, were determined during the induced murine hair cycle by high
      performance liquid chromatography-controlled radioimmuno-assay (SP) or by
      fluorometry (neutral endopeptidase). RESULTS: Both capsaicin and SP induced
      significant hair growth (anagen) in the back skin of telogen mice. This was
      associated with substantial mast cell degranulation. The endogenous SP skin
      concentration showed significant, hair cycle-dependent fluctuations during the
      induced murine hair cycle, which were largely independent of the activity of
      neutral endopeptidase. CONCLUSIONS: SP may play a role in the neural control of
      hair growth. Whereas this pilot study does not address the underlying mechanisms
      of action, it demonstrates that SP has potential as a hair growth-stimulatory
      agent in vivo, and serves as a basis for exploring the role of tachykinins in
      epithelial-mesenchymal-neuroectodermal interaction systems like the hair
      follicle.

PMID- 7518881
TI  - Agarose infiltration improves morphology of cryostat sections of lung.
AB  - BACKGROUND: Optimal morphology and immunohistochemistry of the lung requires the
      organ to remain fully distended. When the lung is prepared for frozen sections,
      especially during the stage of cryoprotection, liquid fixatives leak out and the
      lung tends to collapse. We sought to develop a new technique to improve the
      morphology of frozen sections of the lung while facilitating tissue handling and
      immunoreactivity. EXPERIMENTAL DESIGN: Human, fetal sheep and adult rat lungs
      were distended with 1% low temperature melting agarose and vessels were perfused
      with a 1% paraformaldehyde solution. RESULTS: The agarose infiltration permitted
      easy handling of the lung tissue, and maintained lung architecture during
      cryoprotection. Agarose infiltration and paraformaldehyde fixation provided
      excellent morphology, that was comparable to paraffin-embedded tissue. The
      structural preservation was especially noticeable with human lung that remained
      well distended with the agarose technique. Because of the mild fixation and good
      morphology, precise localization of antigenic sites was possible for the
      surfactant proteins SP-A, SP-C and SP-D, cytokeratin, and alveolar macrophage
      markers. CONCLUSIONS: This procedure can improve special fixation and embedding
      protocols for lung immunocytochemistry and immunofluorescence.

PMID- 7518882
TI  - Tumor-associated macrophages in neoplastic progression: a paradigm for the in
      vivo function of chemokines.

PMID- 7518883
TI  - Functional glucocorticoid receptor modulates pancreatic carcinoma growth through
      an autocrine loop.
AB  - Several peptide hormones have been shown to influence growth and function in
      pancreatic carcinoma and have given evidence for an autocrine feedback loop
      governing the proliferation of these malignant cells. Conversely, steroid
      hormones including glucocorticoids have been shown to inhibit the growth of
      pancreatic cancer cells; however, the prevalence of the glucocorticoid receptor
      or its mechanism of growth suppression in these tumors is unknown. The ability of
      growth factors thought to be active in this autocrine loop to reverse the
      glucocorticoid-induced growth inhibition was studied in vitro in a human
      pancreatic adenocarcinoma (HPAC) cell line with a well-characterized
      glucocorticoid receptor (GR). The glucocorticoid dexamethasone (DEX) inhibited
      growth in a dose-dependent manner as measured by a [3H]thymidine incorporation
      assay as well as an MTT cell proliferation assay. Maximal effects were seen
      within 48 hr at a concentration of 100 nM DEX, suppressing growth to
      approximately 18% of control. When the maximally suppressed DEX-treated cells
      were exposed to exogenous growth factors, they rapidly attained or exceeded the
      growth rate of control cells: insulin-like growth factor = 106%, transforming
      growth factor-alpha = 134%, insulin = 151%, and epidermal growth factor = 187%
      (all P < 0.05, Student's t test). In order to determine the frequency of the GR
      in pancreatic cancer and the clinical relevance of our findings,
      immunohistochemical staining for the GR was performed on 20 human tumors. Twelve
      (60%) of all cancers, as well as all normal pancreatic tissues (n = 4), stained
      positively for cytoplasmic and/or nuclear GR with expression correlating highly
      with degree of tumor differentiation (Kruskal-Wallis test, P < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7518884
TI  - [Report on the current indications for colony stimulating factors (G-CSF and GM
      CSF)].

PMID- 7518885
TI  - [Half-body irradiation].

PMID- 7518886
TI  - Administration time-dependent toxicity of a new immunosuppressive agent,
      tacrolimus (FK 506).
AB  - We have previously shown that blood concentrations of tacrolimus, a new
      immunosuppressive agent, were greater when it was administered orally at 10 pm
      than when it was administered at 10 am in rats. The present study was undertaken
      to examine whether the toxic effects of tacrolimus show administration time
      dependent variations. Male Wistar rats were maintained under conditions of light
      from 7 am to 7 pm and dark from 7 pm to 7 am. Tacrolimus (1 and 4 mg/kg) was
      given orally at 10 am (day trial) or 10 pm (night trial) for 14 days. Blood
      samples were obtained at 24 hours after the final dosage of the agent. Weight
      gain was smaller in the night trial than in the day trial. Plasma concentrations
      of urea and creatinine increased significantly in the night trial while the
      elevations in these parameters were not observed in the day trial. These results
      suggest that the toxic effects of tacrolimus also vary with its time of oral
      dosage.

PMID- 7518887
TI  - Nitric oxide participates in the regulation of pancreatic acinar cell secretion.
AB  - The role of nitric oxide (NO) in the regulation of exocrine secretion was
      investigated in isolated rat pancreatic acini. NO synthase activity was detected
      in the extract of acini and purified by ion-exchange and 2',5'-ADP agarose
      chromatographies. Enzyme activity was determined by conversion of 3H-arginine to
      3H-citrulline, by measurement of nitrite (a breakdown product of NO) and by
      generation of cyclic GMP. Treatment of acini with L-arginine increased nitrite as
      well as cyclic GMP and amylase release, which were prevented by the nitric oxide
      synthase inhibitors N-monomethyl-arginine [NMMA] and NG-nitro-L-arginine [NNA].
      These nitric oxide inhibitors also blocked carbachol-induced amylase release as
      well as elevation of acinar cell cyclic GMP. NNA was a potent inhibitor of
      carbamylcholine-induced amylase release (est. Ki = 2.2 uM). Nitric oxide
      apparently participates significantly in the overall control of pancreatic acinar
      cell secretory function.

PMID- 7518888
TI  - Preparation of conjugated hemoglobins.

PMID- 7518890
TI  - Diversity in molecular mass of the common EDTA-soluble antigens of Clostridium
      chauvoei and Clostridium septicum.
AB  - Common EDTA-soluble antigens of Clostridium chauvoei and C. septicum were
      examined by indirect-immunofluorescence (IFA) and immunoblot analysis. The
      monoclonal antibodies (mAbs) specific for the 35 kDa antigen of C. chauvoei
      strain ATCC 10092 were used. These mAbs reacted with all 11 strains, 6 of C.
      chauvoei and 5 of C. septicum, in IFA. In immunoblot analysis with the mAbs, the
      bands at molecular mass of 35 kDa were found in all C. chauvoei strains, while
      the bands at 36 kDa were found in 4 of 5 strains of C. septicum. These results
      indicate that the 35 kDa antigen of C. chauvoei and the 36 kDa antigen of C.
      septicum possess a similar epitope recognized by the mAb.

PMID- 7518889
TI  - Structural characterization of hemoglobin variants using capillary
      electrophoresis and fast atom bombardment mass spectrometry.

PMID- 7518891
TI  - [Changes in the acaricidal properties of organophosphorus compounds under the
      influence of magnetic resonance treatment].
AB  - The authors demonstrate the possibility of enhancing pesticidal properties of
      some organophosphorus compounds by their single treatment for 40 min by pulsed
      magnetic field, 100 kHz, 10-15 microT with 16 Hz sinusoidal modulation. The
      treatment efficacy is up to 30 days.

PMID- 7518892
TI  - What is it? Case 1, 1994: rapidly progressive aphasia, apraxia, dementia,
      myoclonus, and parkinsonism.

PMID- 7518893
TI  - An unusual cutaneous reaction to anticoagulant therapy.
AB  - Unusual complications of warfarin therapy include cutaneous necrosis and the
      "purple toe syndrome." The latter is more common in men and is not associated
      with vascular compromise; it usually occurs 3 to 8 weeks after warfarin therapy
      is begun and may persist for many months after the medication is discontinued.
      The following is a case of a 63-year-old woman who received warfarin therapy in
      conjunction with heparin for treatment of a left leg deep vein thrombosis.
      Approximately 8 hours after receiving her first dose of warfarin (15 mg), she
      developed acute pain, edema, and discoloration of the entire left leg to the mid
      thigh, most prominent in the left great toe. After discontinuation of warfarin
      therapy, her symptoms completely resolved within 48 hours. This may be a report
      of a new cutaneous lesion associated with anticoagulant therapy.

PMID- 7518894
TI  - The role of nitric oxide in the kainate-induced seizures in mice.
AB  - The effect of L-arginine (L-Arg), D-arginine (D-Arg), N-nitro-L-arginine methyl
      ester (L-NAME) and N-monomethyl-L-arginine (L-NMMA) on the kainate-induced
      seizures was studied in mice. It was found that the precursor of nitric oxide
      (NO) L-Arg (150-600 mg/kg i.p.) increased dose-dependently the dose of kinate
      necessary to produce clonic convulsions in 50% of the animals (CD50). Such an
      anticonvulsant effect was not observed in mice pretreated with D-Arg (150-600
      mg/kg i.p.), the latter drug not being a substrate for NO formation. The
      inhibitors of NO synthase L-NAME and L-NMMA, both administered in doses of 30-30
      mg/kg i.p., reduced the convulsive threshold by decreasing the CD50 of kainate.
      Moreover, L-NAME (3 mg/kg) antagonized the anticonvulsant effect of L-Arg (300
      mg/kg). These results indicate that NO may play a role of an endogenous
      anticonvulsant substance in mice.

PMID- 7518895
TI  - Adrenalectomy alters discrete galanin mRNA levels in the hypothalamus and
      mesencephalon of the rat.
AB  - Using solution and in situ hybridization techniques we have studied the effects
      of adrenalectomy with or without restitution therapy with corticosterone on
      galanin mRNA levels in discrete regions of the male rat brain. Galanin peptide
      levels were also measured using a radioimmunoassay. The solution hybridization
      showed a two-fold increase in galanin mRNA 7 days, but not 14 days, after
      adrenalectomy in the preoptic area including the hypothalamic paraventricular
      nucleus (PVN). No changes were observed in the mediobasal hypothalamus including
      the arcuate nucleus. In situ hybridization showed that the increase in galanin
      mRNA was localized to the PVN and that the arcuate nucleus was not affected. The
      changes observed could be fully counteracted by corticosterone treatment.
      Radioimmunoassay showed decreased galanin levels in the median eminence 14 days,
      but not 7 days, after adrenalectomy and increased levels in the anterior
      pituitary and neurointermediate lobe. The results give evidence for a regional
      regulation of galanin gene expression and galanin peptide synthesis by
      adrenocortical steroids.

PMID- 7518897
TI  - Prostate disease: does someone you care about suffer from it?

PMID- 7518896
TI  - Effectiveness of combining maternal serum alpha-fetoprotein and hCG in a second
      trimester screening program for Down syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of combining hCG and alpha-fetoprotein (AFP)
      with maternal age in a two-analyte maternal serum screening program for Down
      syndrome. METHODS: A prospective study involved the screening of 12,170 maternal
      sera from patients at 14-25 weeks of gestation. The risk for Down syndrome at
      term was calculated from maternal serum hCG and AFP, and maternal age. For women
      36 years of age and younger, a risk of 1:307 or greater was considered screen
      positive. For women over 36, a risk greater than that a priori was considered
      screen-positive. False-positive rates and detection rates were compared with
      those resulting from a screening protocol using only AFP and age. RESULTS: Seven
      hundred eighty-two sera were initially screen-positive (6.4%). Subsequent
      sonography decreased this total to 687 (5.6%), and 467 (3.8%) of these patients
      accepted amniocentesis. Ten cases of Down syndrome and seven other chromosomal
      abnormalities were detected. Follow-up investigations revealed eight additional
      Down syndrome cases that were missed by screening. The identification of 18 Down
      syndrome cases in 12,170 pregnancies corresponds closely with the prediction of
      14.1 Down syndrome births (18.2 second-trimester fetuses) in this population
      calculated from age-dependent risks. The detection rate for Down syndrome was 56%
      (ten of 18 expected cases). Only five of 18 (28%) would have been detected by AFP
      and age alone. CONCLUSION: These results support the mathematical model that hCG
      is the major contributor to the increased sensitivity of multi-analyte screening
      and demonstrate that screening programs can attain substantial improvement in
      detection of second-trimester Down syndrome by adding hCG to AFP and age.

PMID- 7518898
TI  - Dual staining methods for carbohydrates using lectin-gold silver techniques.
AB  - Three dual staining methods were established for the histochemical detection of
      saccharide residues and acidic groupings of carbohydrates in light microscopy.
      The first method consisted of combined lectin-gold silver (LT-G-S) and alcian
      blue (AB) pH 1.0 techniques, whereas the second staining technique was composed
      of LT-G-S and AB pH 2.5 procedures. These two techniques were found to color
      saccharide residues and acidic groupings of carbohydrates in black and blue
      shades respectively, which exhibited a high contrast between the both. The third
      methods, LT1-G-S-LT2-PO-DAB techniques, yielded reaction products of blackish and
      yellowish brown shades, which represented the localizations of two different
      saccharide residues in one and the same section. According to the results of the
      experimental and control procedures, the present three dual staining methods are
      believed to be reliable, reproducible and unusually useful for light microscopic
      histochemical studies on acidic and non-acidic carbohydrates.

PMID- 7518900
TI  - Secretary of Health Noonan addresses health care reform. Interview by Dr. Judith
      McFadden.

PMID- 7518899
TI  - What are you doing for antioxidant protection?

PMID- 7518901
TI  - Dentists extend a hand in "Doctors with a Heart Program".

PMID- 7518903
TI  - Elderly benefit from PDA access to care program.

PMID- 7518902
TI  - Philadelphia program helps handicapped.

PMID- 7518904
TI  - Improving patient relations: guidelines for explaining benefits.

PMID- 7518905
TI  - "...a little bit".

PMID- 7518906
TI  - Chemical dependency and the dental patient.

PMID- 7518907
TI  - Chemical dependency in the dental profession.

PMID- 7518911
TI  - Sexual harassment by dentists.

PMID- 7518910
TI  - Social and ethical empowerment of the profession must come from within the
      profession: interview with Dr. Murial Bebeau. Interview by Dr. Judith McFadden.

PMID- 7518908
TI  - Embracing positivity; combatting dependency through a positive mind set.
      Interview by Dr. Judith McFadden.

PMID- 7518909
TI  - Making personal ethical choices for practical professional survival.

PMID- 7518912
TI  - ADA principles of ethics and code of professional conduct. American Dental
      Association.

PMID- 7518913
TI  - Dental technology and the good-old-days ethics.

PMID- 7518914
TI  - The La antigen inhibits the activation of the interferon-inducible protein kinase
      PKR by sequestering and unwinding double-stranded RNA.
AB  - The La (SS-B) autoimmune antigen is an RNA-binding protein that is present in
      both nucleus and cytoplasm of eukaryotic cells. The spectrum of RNAs that
      interact with the La antigen includes species which also bind to the interferon
      inducible protein kinase PKR. We have investigated whether the La antigen can
      regulate the activity of PKR and have observed that both the autophosphorylation
      of the protein kinase that accompanies its activation by dsRNA and the dsRNA
      dependent phosphorylation of the alpha subunit of polypeptide chain initiation
      factor eIF-2 by PKR are inhibited in the presence of recombinant La antigen. This
      inhibition is partially relieved at higher concentrations of dsRNA. Once
      activated by dsRNA the protein kinase activity of PKR is insensitive to the La
      antigen. We have demonstrated by a filter binding assay that La is a dsRNA
      binding protein. Furthermore, when recombinant La is incubated with a 900 bp
      synthetic dsRNA or with naturally occurring reovirus dsRNA it converts these
      substrates to single-stranded forms. We conclude that the La antigen inhibits the
      dsRNA-dependent activation of PKR by binding and unwinding dsRNA and that it may
      therefore play a role in the regulation of this protein kinase in interferon
      treated or virus-infected cells.

PMID- 7518915
TI  - Sequence and position requirements for uridylate-rich downstream elements of
      polyadenylation signals.
AB  - We have defined the positional and sequence requirements of U-rich downstream
      elements using a simian virus 40 late polyadenylation signal containing a
      substituted downstream region. A UUUUU element will significantly increase the
      efficiency of 3' end processing when placed between 6 and 25 bases downstream
      from the cleavage site. Positions in this interval closer than 15 bases from the
      cleavage site, however, were noticeably less efficient. Placement of the UUUUU
      element between +20 and +25 caused a partial shift in cleavage site usage to a CA
      motif at +4. Mutational analysis indicated that the sequence requirements at
      individual positions of the UUUUU element were somewhat flexible. Changing more
      than one base of the UUUUU sequence, however, severely diminished the ability of
      the element to mediate efficient 3' end processing. Finally, although hnRNP C
      proteins specifically interact with U-rich sequences, this protein--RNA
      interaction is not required for efficient in vitro polyadenylation.

PMID- 7518916
TI  - Targeted RNA fingerprinting: the cloning of differentially-expressed cDNA
      fragments enriched for members of the zinc finger gene family.
AB  - We have developed and applied a modification of an 'RNA Fingerprinting' protocol
      previously published by Welsh and McClelland (Nucleic Acids Research 19: 5275
      5279 1991) such that cDNA fragments which are both differentially-expressed and
      enriched for members of a specific gene family can readily be identified. cDNA
      fragments were amplified with an arbitrary primer initially used in the reverse
      transcription reaction in combination with a member of a primer set which
      corresponded to a conserved region within a specific gene family. This technique
      was used to isolate cDNAs encoding a recently described protein kinase as well as
      an unknown gene that contained a zinc finger. Several other known genes that
      contained a zinc finger domain and that were differentially-expressed were also
      isolated.

PMID- 7518917
TI  - High-affinity RNA ligands to human alpha-thrombin.
AB  - Systematic Evolution of Ligands by EXponential enrichment (SELEX) was used to
      isolate from a population of 10(13) RNA molecules two classes of high affinity
      RNAs that bind specifically to human alpha-thrombin. Class I RNAs are represented
      by a 24-nucleotide RNA (RNA 16.24), and class II RNAs are represented by a 33
      nucleotide RNA (RNA 27.33). RNA 16.24 inhibits thrombin-catalyzed fibrin clot
      formation in vitro. Secondary structures are proposed for these RNAs, revealing a
      novel stem-loop structure for RNA 16.24, comprised of an unusually large 16
      nucleotide loop. Mutants of RNA 16.24 were generated to investigate structural
      features critical to high-affinity binding. Phosphate modification with
      ethylnitrosourea identified regions of the RNAs necessary for electrostatic
      interactions. Competition with heparin suggests that these RNAs bind the
      electropositive heparin-binding site of thrombin. These ligands represent a novel
      class of thrombin inhibitors that may be suitable for therapeutic or diagnostic
      applications.

PMID- 7518921
TI  - Scabies.

PMID- 7518918
TI  - Localization of an RNA binding element of the iron responsive element binding
      protein within a proteolytic fragment containing iron coordination ligands.
AB  - The iron responsive element binding protein (IRE-BP) regulates iron storage and
      uptake in response to iron. This control results from the interaction of the IRE
      BP with the iron responsive element (IRE), a conserved sequence/structure element
      located near the 5' end of all ferritin mRNAs and in the 3' UTR of transferrin
      receptor mRNAs. Proteolysis was used to probe for functional elements of the IRE
      BP. Partial chymotrypsin digestion generates a simple digestion pattern yielding
      fragments of 68, 56, 41, and 30 kDa. The 68 and 30 kDa fragments are derived from
      a single cleavage at Trp623. Further cleavages of the 68 kDa polypeptide yield
      the 56 and 41 kDa peptides. A combination of UV-crosslinking and chymotrypsin
      digestion was used to localize an RNA binding element within the C-terminus of
      the 68 kDa fragment, between amino acid residues 480 and 623. This region
      includes cysteine residues 503 and 506 which have been shown to be required for
      iron-sulfur cluster assembly and for iron regulation of the IRE-BP. Proteolytic
      fragments of the IRE-BP that contain this RNA binding region can be crosslinked
      to the IRE but do not bind with high affinity, suggesting that elements within
      the IRE-BP, in addition to those located between residues 480 and 623, are
      required for high affinity binding to the IRE.

PMID- 7518920
TI  - MutS binding protects heteroduplex DNA from exonuclease digestion in vitro: a
      simple method for detecting mutations.

PMID- 7518919
TI  - Nucleic acid binding and intracellular localization of unr, a protein with five
      cold shock domains.
AB  - The unr gene was identified as a transcription unit located immediately upstream
      of N-ras in the genome of several mammalian species. While this genetic
      organization could be important for the transcriptional regulation of unr and N
      ras, the function of the protein product of unr is unknown. unr is ubiquitously
      expressed and codes for an 85 kDa protein which is not closely related to
      previously characterized proteins. Nevertheless, a search for protein motifs has
      indicated the presence of five 'cold shock domains' within unr, a motif present
      in procaryotic cold shock proteins and in the vertebrate Y box factors. As these
      proteins have been reported to interact with nucleic acids, we investigated
      whether unr could bind to some classes of nucleic acids. We report here that unr
      has a high affinity for single-stranded DNA or RNA and a low affinity for double
      stranded nucleic acids. Its low affinity for double-stranded DNA clearly
      distinguishes unr from the Y box factors. The binding of unr to RNA does not
      appear to depend upon extended sequence motifs but requires some level of
      sequence complexity as unr has only a low affinity for most simple polymers
      including polyA stretches. unr is also characterized by its low affinity for
      double-stranded and structured RNAs. We further determined that unr is mostly
      localized in the cytoplasm, and is in part associated with the endoplasmic
      reticulum. These studies indicate that unr is a novel single-stranded nucleic
      acid binding protein which is likely to be associated with cytoplasmic mRNA in
      vivo.

PMID- 7518922
TI  - The history of a genetic system.
AB  - Although the chromosomal polymorphism for inversions in Drosophila pseudoobscura
      is one of the best studied systems in population genetics, the identity of the
      ancestral gene arrangement has remained unresolved for more than 50 years. There
      are more than 40 gene arrangements, and 4 of them (Standard, Hypothetical, Santa
      Cruz, and Tree Line) have been considered as candidates for the ancestral type.
      We propose a framework of competing hypotheses to distinguish among the
      alternatives. Two conclusions come from contrasting each hypothesis with the
      results from DNA sequencing and restriction mapping. First, not only Standard but
      also Hypothetical can be excluded as the ancestral gene arrangement. Second,
      although either Tree Line or Santa Cruz could be the ancestral type, the
      available data provide greater support for Santa Cruz.

PMID- 7518923
TI  - RNA template-directed RNA synthesis by T7 RNA polymerase.
AB  - In an attempt to synthesize an oligoribonucleotide by run-off transcription by
      bacteriophage T7 RNA polymerase, a major transcript was produced that was much
      longer than expected. Analysis of the reaction indicated that the product
      resulted from initial DNA-directed run-off transcription followed by RNA template
      directed RNA synthesis. This reaction occurred because the RNA made from the DNA
      template displayed self-complementarity at its 3' end and therefore could form an
      intra- or intermolecular primed template. In reactions containing only an RNA
      template, the rate of incorporation of NTPs was quite comparable to DNA-dependent
      transcription. RNA template-directed RNA synthesis has been found to occur with a
      great number of oligoribonucleotides, even with primed templates that are only
      marginally stable. In one instance, we observed a multistep extension reaction
      converting the oligonucleotide into a final product longer than twice its
      original length. Presumably, such a process could have generated some of the RNAs
      found to be efficiently replicated by T7 RNA polymerase.

PMID- 7518924
TI  - Kinetic characterization of intramolecular and intermolecular hammerhead RNAs
      with stem II deletions.
AB  - A method is described to obtain intramolecular cleavage rates for the hammerhead
      ribozyme during in vitro transcription. By avoiding RNA purification and
      renaturation, the potential for formation of inactive conformations of the RNA is
      minimized. By showing that an intramolecular hammerhead and a closely related
      intermolecular hammerhead cleave at the same rate under a given set of
      conditions, we confirm that both reactions probably have the same rate-limiting
      step. An in vitro selection strategy was used to isolate active hammerheads from
      a library of molecules where six randomized nucleotides replaced stem-loop II.
      The sequence and number of nucleotides which replace stem-loop II have large
      effects on hammerhead cleavage activity. The relative activities of three
      sequences selected from the intramolecular library are the same when the
      sequences are transferred into an intermolecular hammerhead background.

PMID- 7518925
TI  - Tumor necrosis factor alpha is an autocrine growth factor for normal human B
      cells.
AB  - Transcription of the human tumor necrosis factor alpha (TNF-alpha) gene is one of
      the earliest events that occurs after stimulation of B or T cells via their
      antigen receptors. Antibody directed at surface immunoglobulin (anti-Ig) on B
      cells has previously been shown to induce a rapid burst of TNF-alpha gene
      transcription, which can be blocked by the immunosuppressants cyclosporin A (CsA)
      and FK506. Here, TNF-alpha gene transcription is shown also to be highly and
      rapidly induced in human B cells after stimulation via the CD40 and interleukin 4
      pathways, which similarly is inhibited by CsA and a panel of CsA or FK506
      analogues that block calcineurin phosphatase activity. Endogenous TNF-alpha
      produced after stimulation was involved in B-cell proliferation since anti-TNF
      alpha monoclonal antibody inhibited both anti-Ig- and anti-CD40-induced B-cell
      proliferative responses. Moreover, addition of TNF-alpha during stimulation
      resulted in augmentation of B-cell proliferation, which was also inhibited by
      anti-TNF-alpha monoclonal antibody. Although lymphotoxin alpha (LT-alpha) mRNA is
      induced by both pathways, it is not blocked by CsA, whereas LT-beta mRNA is
      constitutively expressed in B cells. Thus, TNF-alpha is a necessary autocrine
      growth factor for human B cells stimulated via two independent CsA-sensitive
      pathways and plays a role similar to that of interleukin 2 in T-cell
      proliferation. The autocrine nature of TNF-alpha in activated B cells implies a
      potential role for this cytokine in infection-related polyclonal B-cell expansion
      and in B-cell malignancies.

PMID- 7518926
TI  - Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in
      nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB
      75.
AB  - Female athymic nude mice bearing xenografts of OV-1063 human epithelial ovarian
      cancer cell line were treated with potent luteinizing hormone (LH)-releasing
      hormone (LH-RH) antagonist SB-75 (Cetrorelix; [Ac-D-Nal(2)1, D-Phe(4 CI)2, D
      Pal(3)3, D-Cit6, D-Ala10]LH-RH in which Ac-D-Nal(2) = N-acetyl-3-(2-naphthyl)-D
      alanine, D-Phe(4CI) = 4-chloro-D-phenylalanine, D-Pal(3) = 3-(3-pyridyl)-D
      alanine, and D-Cit = D-Citrulline) or with the agonist [D-Trp6]LH-RH. In the
      first experiment, SB-75 and [D-Trp6]LH-RH were administered in the form of
      microcapsules releasing 60 and 25 micrograms/day, respectively. In the second
      study, the analogs were given by daily s.c. injections in doses of 100
      micrograms/day. In both experiments, tumor growth, as measured by reduction in
      tumor volume, percentage change in tumor volume, tumor burden, and increase in
      tumor doubling time, was significantly inhibited by treatment with SB-75 but not
      with [D-Trp6]LH-RH. Uterine and ovarian weights were reduced and serum LH levels
      decreased by administration of either analog. Chronic treatment with SB-75
      greatly reduced the concentration of receptors for epidermal growth factor and
      insulin-like growth factor I in tumor cell membranes, a phenomenon that might be
      related to tumor growth inhibition. It is possible that the antitumoral effects
      of SB-75 on OV-1063 ovarian cancers are exerted not only through the suppression
      of the pituitary-gonadal axis, but also directly. In view of its strong
      inhibitory effect on the growth of OV-1063 ovarian cancers in vivo, the potent LH
      RH antagonist SB-75 might be considered for possible hormonal therapy of advanced
      epithelial ovarian carcinoma.

PMID- 7518927
TI  - Prolactin activates the interferon-regulated p91 transcription factor and the
      Jak2 kinase by tyrosine phosphorylation.
AB  - The prolactin (PRL) receptor is a member of the family of cytokine receptors that
      lack intrinsic tyrosine kinase activity but contain two conserved cysteines in
      their N-terminal regions and a WSXWS motif adjacent to their transmembrane
      domains. In a manner similar to the interferons (IFNs), exposure of cells to PRL
      results in tyrosine phosphorylation of several cellular proteins and the rapid
      transcriptional induction of the IFN regulatory factor 1 gene. In this
      communication, we demonstrate that treatment of rat Nb2 lymphoma cells with PRL
      activates a latent protein factor so that it binds to an enhancer in the IFN
      regulatory factor 1 gene. This enhancer has been shown to be required for IFN
      gamma-activated expression of this gene. PRL-induced assembly of the DNA binding
      complex, PRL-stimulated factor, required tyrosine phosphorylation. PRL-stimulated
      factor contained at least one protein that was antigenically similar to the p91
      transcription factor, a component of several transcription complexes required for
      cytokine-activated gene expression. PRL not only induced the tyrosine
      phosphorylation of p91 but also induced tyrosine phosphorylation of Jak2, a
      tyrosine kinase required for IFN-gamma-activated gene expression. These results
      provide evidence for a signaling mechanism, some of whose components are shared
      by both PRL and IFN-gamma receptors, that results in the expression of early
      response genes.

PMID- 7518928
TI  - Structural basis of asymmetry in the human immunodeficiency virus type 1 reverse
      transcriptase heterodimer.
AB  - The reverse transcriptase from human immunodeficiency virus type 1 is a
      heterodimer consisting of one 66-kDa and one 51-kDa subunit. The p66 subunit
      contains both a polymerase and an RNase H domain; proteolytic cleavage of p66
      removes the RNase H domain to yield the p51 subunit. Although the polymerase
      domain of p66 folds into an open, extended structure containing a large active
      site cleft, that of p51 is closed and compact. The connection subdomain, which
      lies between the polymerase and RNase H active sites in p66, plays a central role
      in the formation of the reverse transcriptase heterodimer. Extensive and very
      different intra- and intersubunit contacts are made by the connection subdomains
      of each of the subunits. Together, contacts between the two connection domains
      constitute approximately one-third of the total contacts between subunits of the
      heterodimer. Conversion of an open p66 polymerase domain structure to a closed
      p51-like structure results in a reduction in solvent-accessible surface area by
      1600 A2 and the burying of an extensive hydrophobic surface. Thus, the monomeric
      forms of both p66 and p51 are proposed to have the same closed structure as seen
      in the p51 subunit of the heterodimer. The free energy required to convert p66
      from a closed p51-like structure to the observed open p66 polymerase domain
      structure is generated by the burying of a large, predominantly hydrophobic
      surface area upon formation of the heterodimer. It is likely that the only kind
      of dimer that can form is an asymmetric one like that seen in the heterodimer
      structure, since one dimer interaction surface exists only in p51 and the other
      only in p66. We suggest that both p51 and p66 form asymmetric homodimers that are
      assembled from one subunit that has assumed the open conformation and one that
      has the closed structure.

PMID- 7518929
TI  - Identification of immunosuppressant-induced apoptosis in a murine B-cell line and
      its prevention by bcl-x but not bcl-2.
AB  - Cyclosporin A, FK-506, and rapamycin are immunosuppressants often used as
      pharmacological probes to study lymphocyte activation and physiological cell
      death (PCD). Because cyclosporin A and FK-506 are known to prevent PCD in T-cell
      hybridomas and thymocytes, we used these reagents, as well as rapamycin, to
      determine whether they alter the pathway leading to apoptosis in murine WEHI-231
      cells following surface IgM cross-linking. We observed that the
      immunosuppressants themselves induced PCD in WEHI-231 cells, but only in sublines
      susceptible to anti-IgM-mediated apoptosis. PCD was preceded by growth arrest and
      characterized by the DNA fragmentation pattern typical of apoptosis. In B-cell
      lines resistant to anti-immunoglobulin- and immunosuppressant-induced PCD,
      cyclosporin A, FK-506, and rapamycin caused growth arrest. PCD was also induced
      by inhibitors of protein synthesis in WEHI-231 cells but not in the mature B-cell
      line BAL-17. Immunosuppressant-induced and protein synthesis inhibitor-induced
      PCD, but not growth arrest, could be prevented by the overexpression of bcl-xL,
      while transfection with bcl-2 did not affect PCD or cell cycle arrest. These
      results suggest that bcl-2 and bcl-xL may control partially independent systems
      to inhibit PCD in lymphoid cells and that PCD in B and T cells may be
      differentially regulated.

PMID- 7518930
TI  - Improvement of patency in small veins following dextran and/or low-molecular
      weight heparin treatment.
AB  - A clinical dose of dextran 70 had significant antithrombotic effects in small,
      severely traumatized veins, and the effect was enhanced by the addition of low
      molecular-weight heparin. These effects were achieved without bleeding problems
      in this model.

PMID- 7518931
TI  - Strategies for poliomyelitis eradication in developing countries.
AB  - Oral polio vaccine (OPV) delivered only through routine services does not appear
      to interrupt wild virus transmission in the developing countries. The experience
      in the Americas, which despite intensive surveillance has not confirmed any cases
      of paralytic poliomyelitis due to wild poliovirus since 23 August 1991, has shown
      the necessity of delivery of additional doses of OPV through mass campaigns
      targeted at all children under five years of age regardless of their previous
      immunization status and in special mop-up operations targeted at this same age
      group in areas categorized as at high risk of virus transmission, such as those
      that harbored the virus in the recent past. High-risk areas were determined by
      empirical observations, which were subsequently confirmed by molecular
      epidemiology which indicated the presence of several "reservoirs" that helped
      maintain transmission over several years. During mop-ups, OPV is delivered house
      by house. This paper discusses the rationale for the utilization of these
      strategies and outlines the phases for their preparation and evaluation, with
      illustrations from recent experiences with the last cases of paralytic
      poliomyelitis in the Americas.

PMID- 7518932
TI  - A comparison of the palliative effects of strontium-89 and external beam
      radiotherapy in metastatic prostate cancer.
AB  - From 1988 to 1991, 284 patients with prostatic cancer and painful bone metastases
      were treated with either radiotherapy or strontium-89 (200 MBq). Patients were
      first stratified according to suitability for local or hemibody radiotherapy,
      then randomly allocated that form of treatment or strontium-89 (i.v. injection).
      After 4, 8 and 12 weeks pain sites were mapped, toxicity monitored, and all
      additional palliative treatments recorded. There was no significant difference in
      median survival (after > 80% had died); 33 weeks following strontium-89 and 28
      weeks following radiotherapy (p = 0.1). All treatments provided effective pain
      relief; improvement was sustained to 3 months in 63.6% after hemibody
      radiotherapy compared with 66.1% after strontium-89, and in 61% after local
      radiotherapy compared with 65.9% in the comparable strontium-89 group. Fewer
      patients reported new pain sites after strontium-89 than after local or hemibody
      radiotherapy (p < 0.05). Radiotherapy to a new site was required by 12 patients
      in the local radiotherapy group compared with 2 after strontium-89 (p < 0.01),
      although there was no significant difference between hemibody radiotherapy (6
      patients) and strontium-89 (9 patients) in this respect. Platelets and leukocytes
      fell by an average 30-40% after strontium-89 but sequelae were uncommon, and
      other symptoms rare.

PMID- 7518933
TI  - Effect of prochlorperazine as a sensitizer of rat skin on radiation-induced AMP
      metabolism.
AB  - The role of AMP was investigated in radiosensitization by the use of
      prochlorperazine in normal rat skin. AMP metabolism was evaluated by estimating
      the level of activities of 5' nucleotidase vis-a-vis protein, DNA and RNA
      contents in prochlorperazine-treated plus irradiated skin. To study radiation
      induced changes in the skin, the extent of lipid peroxidation was measured in
      terms of enzyme lipid peroxidase. After irradiation, lipid peroxidase activity
      was observed to increase in prochlorperazine-treated rat skin. Subsequently the
      level of 5' nucleotidase was found to decrease in drug-treated plus irradiation
      skin. Similarly, the suppression in the levels of DNA, RNA and protein contents
      increased when the rat skins was irradiated in the presence of sensitizer
      prochlorperazine. The cytological examination, which revealed the extent of the
      lesions occurring in the normal rat skin, and the biochemical examination
      demonstrated increased cellular lethality in prochlorperazine-sensitized skin
      after irradiation. The results suggest that prochlorperazine probably sensitizes
      the normal skin tissues to radiation by inhibiting AMP metabolism via hydroxy
      radical-induced decrease in DNA, RNA and protein metabolism.

PMID- 7518934
TI  - [Antalgic radiotherapy in lumbosacral carcinomatous neuropathies].
AB  - Lumbosacral carcinomatous neuropathy (LCN) may be caused by infiltration or
      compression of the lumbosacral plexi and nerves from intrapelvic or paraaortic
      neoplasms. The authors submitted 23 patients complaining of LCN with CT
      documented intrapelvic or paraaortic tumors to palliative radiotherapy.
      Megavoltage external beam irradiation was administered using a 6-MV linear
      accelerator. Treatment field sizes ranged from 56 cm2 to 235 cm2 (mean: 150.54
      cm2) and encompassed only the site where the disease involved the lumbosacral
      plexus or its branches. > or = 3 Gy/day fractions were used. Twenty-one of 22
      assessable patients (95.4%) obtained LCN pain relief; 19 (86.3%) obtained
      complete LCN pain relief. The median time to pain progression (TPP) was 150 days
      (range: 39-510 days). The median survival was 165 days. Seven patients were LCN
      pain-free at death. Two patients are alive and LCN pain-free. The remaining 12
      patients had recurrent LCN pain: four of them were reirradiated at the site of
      previous neuropathy and only two had partial relief again. The authors conclude
      that it is advisable to submit to palliative radiotherapy the inoperable
      disseminated and/or recurrent cancer patients complaining of LCN, to use large
      fractions not to occupy the extant time of their already short life-expectancy,
      and to design small fields to avoid acute side-effects.

PMID- 7518936
TI  - The Unity and Diversity of Membrane Function. Proceedings of the 15th Conference
      on Biological Membranes. Valais, Switzerland, June 6-10, 1993.

PMID- 7518935
TI  - [Allergic reaction following the administration of aprotinin in mitral valve
      replacement].

PMID- 7518937
TI  - ATP-sensitive K+ channels.

PMID- 7518938
TI  - Molecular mechanisms of inactivation and modulation of sodium channels.

PMID- 7518939
TI  - The voltage sensor for the opening and closing of the sodium channel.

PMID- 7518940
TI  - Modulation of potassium conductances by metabotropic glutamate receptors in the
      hippocampus.

PMID- 7518942
TI  - The 'pump-leak' parallelism in Necturus enterocytes: some cellular and molecular
      insights.

PMID- 7518941
TI  - Morphological differentiation and Ca2+ channel expression in PC12 cells.

PMID- 7518943
TI  - Pump-leak coupling in the amphibian diluting segment.

PMID- 7518944
TI  - Structure and functional properties of an inwardly rectifying ATP-regulated K+
      channel from rat kidney.

PMID- 7518945
TI  - Structure-function relation of a cloned epithelial chloride channel.

PMID- 7518947
TI  - Long-term potentiation and glutamate receptors: a role for protein kinases.

PMID- 7518948
TI  - Expression cloning and characterization of the glutamate transporter in neurons.

PMID- 7518946
TI  - Glutamate induces the release of arachidonic acid by interacting with an atypical
      metabotropic receptor present on mouse brain astrocytes.

PMID- 7518949
TI  - Inhibition of high-affinity glutamate transport in neuronal and glial cells by
      arachidonic acid and oxygen-free radicals. Molecular mechanisms and
      neuropathological relevance.

PMID- 7518950
TI  - Regulation of astrocyte energy metabolism by neurotransmitters.

PMID- 7518951
TI  - Diversity in functional properties and primary structure of neuronal nicotinic
      receptor channels.

PMID- 7518953
TI  - Molecular biology of glutamate receptors. Potentiation of N-methyl-D-aspartate
      receptor splice variants by zinc.

PMID- 7518952
TI  - The pore of voltage-dependent potassium channels.
AB  - Using a combination of electrophysiological and mutational analyses, the pore of
      K+ channels has been localized. Experiments have now been started on the
      mechanism of permeation and the value and limitations of the combined approach
      should soon become apparent.

PMID- 7518956
TI  - Molecular biology and hormonal regulation of vertebrate Na+/H+ exchanger
      isoforms.

PMID- 7518957
TI  - Function of halorhodopsin as a light-driven H+ pump.

PMID- 7518955
TI  - Influence of stilbene disulfonates on the accessibility of the substrate-binding
      site for anions in the band 3 protein (AEB1).

PMID- 7518954
TI  - Structures involved in binding, gating, and conduction in nicotinic acetylcholine
      receptors.

PMID- 7518958
TI  - Na,K-ATPase: structure-function studies.

PMID- 7518960
TI  - Osmoregulation of Na-coupled organic osmolyte transporters.

PMID- 7518959
TI  - The Na, K, C cotransporter of shark rectal gland.

PMID- 7518962
TI  - A molecular view of renal Na-dependent phosphate transport.

PMID- 7518963
TI  - Porins from bacterial outer membranes.

PMID- 7518964
TI  - The X-ray structures of Escherichia coli porin OmpF and ovine prostaglandin
      synthase: implications for membrane structure.

PMID- 7518961
TI  - Structure and function of sodium-coupled neurotransmitter transporters.

PMID- 7518967
TI  - Surgery for cancer of the esophagus.

PMID- 7518966
TI  - FK 506 (Tacrolimus) metabolism by rat liver microsomes and its inhibition by
      other drugs.
AB  - The in vitro metabolism of FK 506 and its inhibition by other drugs was studied
      with hepatic microsomes from rats pre-treated with dexamethasone, a selective
      cytochrome P-450 IIIA inducer. Nonspecific inhibitors of cytochrome P-450, such
      as ketoconazole, itraconazole, fluconazole and SKF 525 A, and most of the
      cytochrome P-450 IIIA specific substrates used in this study significantly
      inhibited FK 506 metabolism. Although cyclosporine is a known substrate of
      cytochrome P-450 IIIA, it had no effect on FK 506 metabolism. Cytochrome P-450 II
      substrates had minimal but significant effect on FK 506 metabolism. This data
      supports our earlier observations that FK 506 metabolism is mediated
      predominantly by the steroid inducible cytochrome P-450 IIIA enzyme subfamily.
      The results of this study indicate that in transplant patients there is a
      potential for an interaction of FK 506 with other drugs that are metabolized by
      the cytochrome P-450 IIIA subfamily or those that alter the activity of
      cytochrome P-450 IIIA subfamily. Careful monitoring and FK 506 dosing adjustment
      may be necessary to maintain therapeutic concentration and minimize toxicity in
      patients receiving this agent.

PMID- 7518968
TI  - Radiotherapy alone in esophageal carcinoma: current management and future
      directions of adjuvant, curative and palliative approaches.

PMID- 7518965
TI  - Soluble CD14 (sCD14) levels in patients with multiple organ failure (MOF).
AB  - We measured soluble CD14 (sCD14), plasma endotoxin, tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, and interferon-gamma (IFN
      gamma) in patients with multiple organ failure (MOF). The sCD14 level was
      significantly higher in septic patients with MOF than that in those without MOF
      and also higher in non-septic trauma patients with MOF than that in those without
      MOF. In the septic group with MOF, the sCD14 level correlated significantly with
      the TNF-alpha level but not the plasma endotoxin, IL-1 beta, IL-6, or IFN-gamma
      level. These results suggest that the sCD14 level reflects the degree of
      pathophysiology and that TNF-alpha is involved in stimulating sCD14 production.

PMID- 7518969
TI  - Serological responses induced in mice by immunogenic proteins and by protein
      respiratory allergens.
AB  - It is known that a variety of materials, including both low molecular weight
      chemicals and proteins, is able to induce occupational respiratory allergy. We
      have shown previously that exposure of mice to chemical respiratory sensitizers
      results in both a marked increase in the serum concentration of IgE and the
      appearance of specific IgE antibody. In the present study we have examined the
      characteristics of immune responses induced in mice following intraperitoneal
      exposure to 3 protein respiratory allergens, ovalbumin (OVA), a lipase from
      Aspergillus oryzae (LP) and an amylase from Bacillus subtilis (AM) and to a
      fourth protein, bovine serum albumin (BSA), which is considered usually not to
      cause respiratory sensitization. Under conditions where all proteins provoked IgG
      antibody responses, only OVA, LP and AM elicited specific IgE antibody. As judged
      by passive cutaneous anaphylaxis (PCA) assay, BSA failed to induce an IgE
      response. In contrast to chemical respiratory sensitizers, the protein allergens
      examined here failed to cause a substantial increase in the serum concentration
      of IgE; OVA and AM induced no increase in serum IgE and LP only a comparatively
      modest increase relative to control values. In conclusion, these data demonstrate
      that while protein respiratory allergens are able to provoke specific IgE
      antibody, they fail to cause a marked increase in the concentration of this
      immunoglobulin in the sera of treated mice. It would appear, therefore, that the
      mouse IgE test, which seeks to evaluate chemical respiratory sensitization
      potential as a function of induced changes in the concentration of serum IgE,
      will be inappropriate for the identification of protein respiratory allergens.
      Nevertheless, identification of protein allergens may be possible by exploiting
      the observations reported here that such proteins induce in mice specific IgE
      antibody responses.

PMID- 7518970
TI  - Spontaneous echo contrast and hemorheologic abnormalities in cerebrovascular
      disease.
AB  - BACKGROUND AND PURPOSE: Spontaneous echo contrast (SEC) is thought to represent a
      risk factor for cardioembolic stroke. In vitro studies suggest that SEC results
      from interaction between red cells and fibrinogen. To better understand the
      relation between SEC and stroke and to investigate the in vivo genesis of SEC, we
      examined the relation between SEC, the constituents of the blood, and plasma and
      serum viscosity in patients with acute stroke or chronic cerebrovascular disease.
      METHODS: Fifty patients with acute stroke or chronic cerebrovascular disease
      referred for transesophageal echocardiogram (TEE) were studied by transthoracic
      echocardiography and TEE. Complete blood count, fibrinogen, albumin, gamma
      globulin, and plasma and serum viscosity determinations were made. Left atrial
      SEC was graded as absent, mild, or marked by means of TEE. RESULTS: SEC was
      absent in 31 patients, mild in 10 patients, and marked in 9 patients. Higher
      grade of SEC was associated with a significantly greater percentage of patients
      with atrial fibrillation and larger left atrial dimension. Atrial fibrillation
      was present in 23% of the patients in the SEC absent group, 50% of the patients
      in the mild SEC group, and 78% of the patients in the marked SEC group (P < .01).
      Left atrial diameter averaged 3.8 +/- 0.6 cm in the SEC absent group, 4.3 +/- 1.1
      in the mild SEC group, and 4.9 +/- 0.7 in the marked SEC group (P < .001).
      Hematocrit, white blood cell count, and platelet count did not differ among the
      three groups. Fibrinogen, gamma-globulin, plasma viscosity, and serum viscosity
      values were all significantly higher in the presence of SEC (P < .05). Fibrinogen
      values were 361 +/- 97 mg/dL in the SEC absent group and 427 +/- 135 mg/dL in the
      marked SEC group. gamma-Globulin levels were 0.75 +/- 0.23 g/dL in the SEC absent
      group and 1.06 +/- 0.48 g/dL in the marked SEC group. Both plasma viscosity (1.97
      cp) and serum viscosity (1.64 cp) were higher in the marked SEC group than in the
      SEC absent group (1.77 and 1.50 cp, respectively). CONCLUSIONS: In patients with
      acute stroke or chronic cerebrovascular disease, the severity of SEC was not
      related to albumin, hematocrit, white cell count, or platelet count but rather to
      elevated fibrinogen levels and concomitant increases in both plasma and serum
      viscosity. Moreover, increasing grade of SEC was associated with significantly
      increased left atrial diameter and a higher percentage of patients in atrial
      fibrillation.

PMID- 7518971
TI  - Correlation between angiogenesis and basic fibroblast growth factor expression in
      experimental brain infarct.
AB  - BACKGROUND AND PURPOSE: Cerebral endothelial cells are quiescent under normal
      conditions; they are stimulated to proliferate around an infarct, although the
      mechanism is unclear. In the present study we explored the relation between
      angiogenesis and the expression of basic fibroblast growth factor (bFGF) by
      participating cells in brain infarct. METHODS: Brain infarct was created in rats
      by ligation of a branch of the left middle cerebral artery followed by permanent
      occlusion of the left common carotid artery and temporary occlusion of the right
      common carotid artery. The brains were removed after 1 to 14 days and studied
      with histological and immunohistochemical methods. Bromodeoxyuridine (BRdU) was
      used as an S-phase marker for the proliferative cells. RESULTS: Enhanced bFGF
      immunoreactivity was observed in neurons adjacent to the infarct after 1 day, and
      the change subsequently spread to distant neurons in the ipsilateral hemisphere.
      After 2 days blood vessels and glial cells around the infarct began to
      incorporate BRdU. During the first week new capillaries accompanied by
      macrophages extended into the infarct. The macrophages, endothelial cells, and
      reactive astrocytes expressed mild to moderate bFGF immunoreactivity.
      CONCLUSIONS: The spatial and temporal correlation between bFGF expression and
      angiogenesis in conjunction with the well-known biological properties of bFGF
      suggest that bFGF produced by neurons, macrophages, and glial cells may
      participate in angiogenesis in brain infarct.

PMID- 7518972
TI  - Spinal cord infarcts during long-term inhibition of nitric oxide synthase in
      rats.
AB  - BACKGROUND AND PURPOSE: Chronic hypertension is a major predisposing factor for
      stroke in humans. It has recently been shown that long-term inhibition of nitric
      oxide synthase activity causes a gradual time-dependent increase in arterial
      blood pressure in rats. We used this new animal model of chronic hypertension to
      study the occurrence and spatial features of infarcts in the central nervous
      system. METHODS: Rats were treated with a nitric oxide synthase inhibitor, NG
      nitro-L-arginine methyl ester, dissolved in the drinking water at 50 mg/kg per
      day for 11 weeks. The brains and spinal cords of hypertensive rats with and
      without motion disturbances were processed for standard microscopic examination.
      RESULTS: Seventy-nine percent of the hypertensive rats showed motion
      dysfunctions, especially front leg paralysis, and/or died suddenly when their
      systolic blood pressure reached approximately 215 mm Hg after approximately 7
      weeks of treatment. All of the hypertensive rats with stroke had spinal cord
      infarcts (90% at the cervical or cervicothoracic level) either alone or combined
      with brain lesions (30%). These structural alterations ranged from focal areas of
      pale, spongy tissue to large necrotic sites with vascular alterations, including
      thickened or fibrinoid degenerated vessel wall, macrophage invasion, and reactive
      astrocytes. CONCLUSIONS: Infarcts occurred in the central nervous system with a
      high incidence in the spinal cord of hypertensive rats in which nitric oxide
      synthase was chronically blocked. This location of the hypertensive
      neuropathologic sequelae contrasts with the model of stroke-prone spontaneously
      hypertensive rats. The results suggest that nitric oxide is a key factor in
      spinal cord arteriolar vasomotion and structure in rats.

PMID- 7518973
TI  - Brain nitric oxide synthase activity in normal, hypertensive, and stroke-prone
      rats.
AB  - BACKGROUND AND PURPOSE: Nitric oxide-mediated cerebral vasodilation is altered in
      spontaneously hypertensive stroke-prone rats. Stroke predisposition in this
      strain could be related to a genetic defect of brain nitric oxide synthase, the
      enzyme responsible for nitric oxide production. We tested the hypothesis that
      brain nitric oxide synthase activity is altered in spontaneously hypertensive
      stroke-prone rats compared with spontaneously hypertensive or Wistar-Kyoto rats.
      METHODS: A colony of spontaneously hypertensive stroke-prone rats was bred, in
      which the rate of neurological events under salt load was assessed. In a separate
      cohort of animals brain nitric oxide synthase activity was measured in
      spontaneously hypertensive stroke-prone rats (n = 6) and in spontaneously
      hypertensive (n = 6) and genetically related Wistar-Kyoto rats (n = 6). Calcium
      dependency of nitric oxide synthase was also assessed in cortical brain samples
      from the three rat strains to determine if altered calcium-dependent activation
      of nitric oxide synthase was present. RESULTS: Brain nitric oxide synthase
      activity was highest in the cerebellum (eg, spontaneously hypertensive stroke
      prone rats: cerebral cortex, 10.6 +/- 0.9; cerebellum, 50.1 +/- 12.0; brain stem,
      14.7 +/- 10.3 pmol/mg protein per minute); however, there was no difference among
      the three rat strains in any region (eg, cerebral cortex: spontaneously
      hypertensive stroke-prone, 10.6 +/- 0.9; spontaneously hypertensive, 10.8 +/-
      0.5; Wistar-Kyoto, 10.9 +/- 0.7 pmol/mg protein per minute) or at any calcium
      concentration tested. CONCLUSIONS: A genetic defect of brain nitric oxide
      synthase is unlikely to be the cause of stroke predisposition in spontaneously
      hypertensive stroke-prone rats.

PMID- 7518974
TI  - Neurotoxicity after orthotopic liver transplantation. A comparison between
      cyclosporine and FK506.
AB  - Neurotoxicity represents a serious complication following orthotopic liver
      transplantation. Neurotoxicity may be evoked by various perioperative factors or
      develop due to drug-specific toxicity of immunosuppression. We evaluated the
      incidence of neurotoxicity in 121 patients, 61 randomly assigned to FK506 and 60
      to CsA-based immunosuppression. The incidence of moderate or severe neurotoxicity
      was markedly higher in patients treated with FK506 in the early postoperative
      period (21.3% vs. 11.7% in patients receiving CsA), after retransplantation (100%
      vs. 0% in patients receiving CsA), and late (8 of 10 patients; P < or = 0.05 vs.
      CsA). Furthermore late neurotoxicity was highly associated with severe infections
      and MOFS, which had a lethal outcome in more than 50% of the patients. Patients
      who subsequently died developed neurologic symptoms in 67% of the cases. These
      patients also experienced moderate or severe neurotoxicity significantly more
      often in the early postoperative period compared with patients with a successful
      outcome (50% vs. 17.3%; P < or = 0.01). However, various blood and serum
      parameters, including ALT, bilirubin, urea, creatinine and glucose, when analyzed
      alone or in multivariate fashion, also correlated significantly with the
      incidence and severity of early postoperative neurotoxicity, indicating that
      neurotoxicity following LTX may be caused by various factors and is not
      exclusively a drug-specific side effect of immunosuppression.

PMID- 7518975
TI  - Nephrotoxicity following orthotopic liver transplantation. A comparison between
      cyclosporine and FK506.
AB  - Nephrotoxicity represents a serious side effect of immunosuppression following
      liver transplantation. In order to compare the nephrotoxic action of CsA and
      FK506 in a clinical setting, we evaluated the incidence of early and late
      nephrotoxicity in 121 patients, 60 of whom were randomly assigned to CsA- and 61
      to FK506-based immunosuppression. Early postoperative renal insufficiency
      (between PODs 0 and 30; SCr 1.5-3 mg/dl) was observed to a similar extent in
      patients treated with CsA (38.3%) and FK506 (42.6%). Early postoperative acute
      renal failure (ARF) (SCr > 3 mg/dl) was observed in 18.0% of patients in the
      FK506 treatment group and 18.3% of patients receiving CsA therapy. Approximately
      half the patients with ARF required hemodialysis (CsA: 11.7%; and FK506: 8.2%).
      All patients with early postoperative ARF requiring hemodialysis survived for
      more than one year. New onset of late ARF (between PODs 30 and 365) was observed
      in 6.6% of patients receiving FK506 therapy and in 1.7% in the CsA treatment
      group as a result of severe infection with multiple organ failure syndrome
      (MOFS). There was 100% mortality in patients with late ARF requiring
      hemodialysis. Etiology and prognosis of early and late ARF seem to be completely
      different. Early ARF was associated with severe coagulopathy and a rise in
      bilirubin and free hemoglobin, and was accompanied by impaired liver function.
      Mean onset of hemodialysis in CsA-treated patients was POD 1 and in FK506-treated
      patients POD 6, which disclosed a different time course of drug-specific
      nephrotoxicity of CsA and FK506 in early ARF. In contrast, late ARF occurred in
      both treatment groups only as a part of the MOFS in association with severe
      infections, an observation consistent with the assumption of
      overimmunosuppression rather than a primary nephrotoxic effect. Late renal
      insufficiency appeared in 23.3% of CsA- and in 29.4% of FK506-treated patients,
      and represented a slowly progressing form of drug-specific nephrotoxicity of CsA
      and FK506. These preliminary results demonstrate a similar outcome in terms of
      both early and late nephrotoxicity, but longer follow-up will delineate the
      overall efficacy and toxicity in humans.

PMID- 7518977
TI  - Characterization of a monoclonal antibody recognizing an epitope designated as
      canine leukocyte-associated antigen.
AB  - An IgG1 monoclonal antibody (mAb), designated as 15F1.5, was generated against
      surface determinants of a dog peripheral blood-derived PHA-induced IL-2-dependent
      T cell line. It reacted with 65-80% of peripheral blood mononuclear cells
      (PBMCs), 90-95% of polymorphonuclear cells (PMNs), 65-70% of thymocytes, 85-95%
      of Thy-1 positive cells and 85-95% of IL-2-dependent T lymphoid cells in flow
      cytometry. It was nonreactive with peripheral blood red cells and platelets. It
      immunoprecipitated 95 and 150 Kd proteins derived from detergent solubilized
      lymphocyte membranes. Indirect immunofluorescent and immunoperoxidase staining of
      frozen tissue sections demonstrated positive reactivity to cells in lymphoid but
      not nonlymphoid tissues. The 15F1.5 antibody was not directly mitogenic for
      PBMC's. It caused significant decrease (P < or = 0.05) in the lymphoproliferative
      response to T-dependent B cell mitogens, such as pokeweed mitogen (PWM) and
      staphage lysate (SPL), without significant effects on responses to the T cell
      mitogens, phytohemagglutinin (PHA), and concanavalin A (Con A). The mixed
      lymphocyte culture (MLC) response and both the proliferative and effector arms of
      the cell-mediated cytotoxicity reactions (CMC) were inhibited in a dose-dependent
      manner. The mAb also inhibited the auto- and allolymphoproliferative reactivity
      of mixed lymphocyte kidney or islet cell cultures (MLKC and MLIC), and the
      adhesion of T lymphoblasts and PMA-treated PMNs to endothelial cells. In vivo
      administration of the 15F1.5 (20 mg/day for 5 days) caused an immediate and
      prolonged reduction in MLC responses, associated with cell binding of the mAb to
      PBMC and epitope modulation during the course of treatment, as indicated by flow
      cytometry. These results suggest that 15F1.5 is an immunomodulating antibody
      reacting with canine LFA-1. Thus, this mAb would be useful in studying the role
      of LFA-1/ICAM-1 in graft rejection as well as other inflammatory responses. It
      would also allow the use of an animal model to investigate the immunoregulatory
      effects of in vivo administration of anti-CD11/CD18 antibodies in organ/tissue
      transplants.

PMID- 7518978
TI  - PSA density and early prostate cancer detection.

PMID- 7518976
TI  - In vivo effects of the immunosuppressant 15-deoxyspergualin on hematopoiesis in
      murine allogeneic bone marrow chimeras. Its thrombopoietic activity and reversal
      of adverse effects with granulocyte colony-stimulating factor and/or
      erythropoietin.
AB  - When 15-deoxyspergualin (DSG), a potent immunosuppressant, was administered into
      [BALB/c-->C3H/He] bone marrow chimeras from day 14 to day 25, increased
      thrombopoiesis was induced on day 20 to day 33, accompanied by marked
      leukocytopenia and anemia. The mean platelet counts in DSG-treated and control
      [BALB/c-->C3H/He] bone marrow chimeras on day 25 were (114.1 +/- 0.5) x
      10(4)/microliter versus (58.6 +/- 2.6) x 10(4)/microliter (1.9-fold increase).
      Colony-forming units-megakaryocyte (CFU-Meg) were not significantly increased in
      DSG-treated bone marrow chimeras. Colony-forming units-granulocyte/macrophage
      (CFU-GM) and burst-forming units-erythroid (BFU-E) were decreased during DSG
      treatment whereas CFU-Mix colony formations were rather increased, and more
      primitive hematopoietic progenitor cells (highly proliferative potential colony
      forming units [CFU-HPP]) were not decreased in the same time period. Since CFU-GM
      and BFU-E colony formations were increased immediately after the cessation of DSG
      treatment, followed by the rebound of leukocyte counts and the recovery of
      hemoglobin (Hb) levels, the leukocytopenia and anemia appeared to be induced by a
      cytostatic effect of DSG. The adverse effect of DSG was partly reversed by the
      simultaneous administration of granulocyte colony-stimulating factor (G-CSF)
      and/or erythropoietin (EPO), suggesting the need for the administration of these
      cytokines in the case of bone marrow transplants treated with DSG. Furthermore,
      it was of note that DSG modulated hematopoiesis and stimulated the production of
      thrombopoietin (TPO)-like cytokine(s) as well as interleukin-3 (IL-3).

PMID- 7518979
TI  - Nonseminomatous germ cell tumors of the testis: current concepts and
      controversies.

PMID- 7518981
TI  - Safety assessment of terazosin in the treatment of patients with symptomatic
      benign prostatic hyperplasia: a combined analysis.
AB  - OBJECTIVES: This study reviews and assesses the safety of terazosin for the
      treatment of symptomatic benign prostatic hyperplasia (BPH). METHODS: Six placebo
      controlled trials (including two unpublished series) involving 996 patients
      provide the database for this evaluation. Six hundred thirty-six patients
      received terazosin from 1 to 20 mg daily for a total of 229 patient-years of
      exposure to terazosin. The most common final dose of terazosin was 10 mg once
      daily. RESULTS: Side effects were generally mild or moderate in severity and
      resolved following cessation of therapy. Side effects resulted in premature
      withdrawal in 9% of terazosin-treated patients and 7% of placebo-treated patients
      (difference not significant). Dizziness (2.0%) and headache (1.1%) were the most
      common symptoms leading to premature withdrawal from the studies. Although
      postural symptoms and dizziness were slightly more common in those terazosin
      treated patients 65 or more years old compared with patients less than 65 years
      old, this difference was not statistically significant. Only 4 of the 636
      patients (0.6%) had syncopal episodes; 2 of these occurred at initiation of
      terazosin therapy or at dose escalation. Minimal reductions in blood pressure
      were observed in normotensive patients and patients with hypertension controlled
      by concomitant medication, whereas patients with untreated hypertension had
      substantial decreases in both systolic and diastolic blood pressures.
      Statistically significant increases in high density lipoprotein to cholesterol
      ratio and reductions in total cholesterol, low density lipoprotein, and
      triglycerides were also seen. CONCLUSIONS: This combined analysis suggests that
      terazosin can be safely administered to both normotensive and hypertensive
      patients with symptomatic BPH.

PMID- 7518982
TI  - Transurethral microwave thermotherapy (TUMT) in benign prostatic hyperplasia:
      placebo versus TUMT.
AB  - OBJECTIVES: A prospective, randomized placebo-controlled study was designed to
      exclude a placebo response in transurethral microwave thermotherapy (TUMT).
      METHODS: During a sham procedure, the microwave applicator was installed in the
      urethra as in the real TUMT treatment and a complete procedure was simulated by
      the microwave delivery system (Prostatron). Any patient who entered this study
      had the option to request a second real TUMT treatment if, 3 months after the
      initial procedure, his condition had not improved. RESULTS: A total of 48
      patients were available for evaluation at 3 months and 28 at 6 months. The TUMT
      group had an average decrease of 7.3 points (from 13.2 to 5.9) in the Madsen
      symptom score, an average increase in flowrate of 3.4 mL/s (9.6 to 13.0), and an
      increase in voiding percentage of 9.6% (81.7 to 91.3). All improvements were
      statistically significant. In the sham group, the average Madsen score decreased
      from 12.1 to 8.2 points, the average flowrate decreased from 9.7 to 9.5 mL/s, and
      the voiding percentage increased from 80.8% to 84.3%. Only the change in symptom
      score was significant. In both groups, observations at the 3-month follow-up were
      similar to those after 6 and 12 months. Patients who had TUMT after sham
      treatment showed similar significant changes in symptom score and peak flow as
      observed in the original TUMT group. Patients who did not respond favorably to a
      first TUMT did not experience improvement after a second TUMT. CONCLUSIONS: A
      placebo effect, although minimal, exists. This placebo response, however,
      accounts for little of the observed benefit of TUMT.

PMID- 7518983
TI  - Morphometric quantitation of stroma in human benign prostatic hyperplasia.
AB  - OBJECTIVES: Human benign prostatic hyperplasia (BPH) consists of three major
      histologic components: stroma, epithelium, and luminal space. For the relief of
      bladder outlet obstruction caused by BPH, quantitation of the histologic
      composition of BPH may aid in selecting treatment. To investigate variation
      between patients in the stromal percentage of BPH, we performed quantitative
      morphometry on specimens from patients with clinically significant bladder outlet
      obstruction obtained by three procedures: open prostatectomy, transurethral
      resection of the prostate (TURP), and prostate needle biopsy (PNB) just prior to
      TURP. METHODS: Ten specimens obtained by each surgical procedure were analyzed.
      Specimens were stained with antibody to muscle-specific actin to mark the stroma;
      quantitation of stroma was accomplished by computer image analysis. RESULTS: The
      percentage of stroma in all BPH cases ranged from 49.9% to 76.7% (mean, 65.4%, SD
      = 7.4). No significant difference was observed when comparing samples obtained by
      the three procedures (p = 0.70). Smooth muscle stromal composition was also
      quantified in PNB specimens. For these samples, a significant inverse
      relationship was found between the percentage stroma in the biopsy and the
      percentage of stroma composed of smooth muscle (r2 = 0.49; p = 0.021).
      CONCLUSIONS: The data demonstrated that the largest component of BPH was stroma,
      which comprised approximately 50% to 75% of the total hyperplastic tissue. The
      mean and range of stromal percentage were similar whether investigating large
      tissue samples from open prostatectomies or small samples from needle biopsies.
      PNB data indicated that an increased percentage of stroma may be due to increased
      nonmuscular elements in the stroma.

PMID- 7518980
TI  - Identification of a mucin layer in the urinary bladder.
AB  - OBJECTIVES: The specific goal of this study was to establish a simple
      histochemical technique by which the glycosaminoglycan (GAG) lining in the rabbit
      bladder can be routinely identified. METHODS: Rabbit bladder tissues were fixed
      in zinc formal, 10% neutral buffered formalin (NBF), 20% NBF, 40% NBF, 2% calcium
      acetate in 10% NBF, 2% sodium acetate in 10% NBF, 1% cetylpyridinium chloride in
      10% NBF, 80% alcohol, histochoice, and 2.5% glutaraldehyde in 0.1 M cacodylate
      buffer. The following histochemical staining was used: mucicarmine/metanil
      yellow, colloidal iron, deamination followed by colloidal iron, periodic acid
      Schiff, saponification followed by colloidal iron, Alcian blue (AB) at variable
      pH values, combined aldehyde-fuchsin/AB, performic acid/AB, AB/Alcian yellow,
      high temperature (60 degrees C) methylation/saponification/AB, and AB/nuclear
      fast red at pH 5.8 with critical electrolyte concentrations with or without
      deamination. RESULTS: AB with sodium acetate buffer at pH 5.8 containing 0.6 M or
      0.8 M magnesium chloride (MgCl2) showed a well-defined thin GAG lining on the
      surface of the urothelium, whereas histochemical staining used by previous
      investigators showed only patchy distribution. There was no observable difference
      due to the gender, fixative, or region of the bladder from which the tissue was
      obtained. CONCLUSIONS: A very thin lining of GAG exists in the rabbit bladder
      which can be localized by AB in sodium acetate buffer at pH 5.8 containing 0.6 M
      or 0.8 M MgCl2 but not by conventional histochemical techniques. This method now
      can be applied to answer many questions regarding urothelial function.

PMID- 7518984
TI  - Characteristics of prostatic infarcts and their effect on serum prostate-specific
      antigen and prostatic acid phosphatase.
AB  - OBJECTIVES: To determine how prostatic infarcts affect serum prostate-specific
      antigen (PSA) and prostatic acid phosphatase (PAP) levels. METHODS: Two hundred
      eighteen clinically benign, whole prostates were obtained at autopsy, completely
      sectioned, and examined histologically. PSA and PAP levels were determined from
      premortem serum. RESULTS: Six of the 218 (2.8%) prostates had infarcts. The
      infarcts were usually multiple and usually located in the central and/or middle
      concentric zones of the middle third of the prostate without a preference for a
      particular lobe. Serum PSA by immunoradiometric assay were elevated in all 6
      cases. Serum PAP by both enzymatic assay (ACA), and immunoradiometric assay were
      available for 5 cases and were elevated by both methods in 2 cases, approached
      elevated levels by both methods in 1 case, and were normal by both methods in 2
      cases. The PSA and PAP levels appeared to be affected more by the age than by the
      size of the infarct. CONCLUSIONS: Prostatic infarcts elevate PSA levels more
      frequently than PAP levels, and prostatic infarcts may be responsible for some
      unexplained elevations of serum PSA and PAP levels.

PMID- 7518985
TI  - Development of a highly sensitive immunochemiluminometric assay for prostate
      specific antigen.
AB  - OBJECTIVES: An assay is described for measuring very low concentrations of
      prostate-specific antigen (PSA) which could be used to reliably monitor patients
      with radical prostatectomies potentially to detect early recurrence of prostate
      cancer. METHODS: A combination of immobilized and acridinium ester-labeled
      monoclonal antibodies was used to develop a two-step, 90-minute chemiluminometric
      assay. The reference standards for the serum assays were prepared by adding
      patient sera with a high concentration of PSA to base pools of female sera, which
      were selected because of low background counts and good recovery of added PSA.
      The assay was standardized to match the Abbott IMx PSA Assay. RESULTS: The serum
      based analytic detection limit (calculated as response 2.5 standard deviations
      [SD] above the zero standard) is 0.004 ng/mL, whereas the "biologic detection
      limit" (calculated as 2.0 SD above the analytic detection limit) is 0.008 ng/mL.
      The assay is highly reproducible with interassay coefficients of variation (CV)
      under 12% down to 0.02 ng/mL, qualifying this as a "second generation" assay (eg,
      CV < 20% at 0.05 ng/mL). CONCLUSION: This assay can measure very low
      concentrations of PSA in plasma and a wide range of PSA concentrations in urine.
      This assay will provide a valuable analytic tool for the future evaluation of the
      clinical utility of "ultrasensitive" PSA measurements for the management of
      prostate cancer.

PMID- 7518986
TI  - Immunohistochemical localization of prostate-specific markers within the
      accessory male sex glands of Cowper, Littre, and Morgagni.
AB  - OBJECTIVES: The aim of the study was to explore possible production of prostate
      specific markers by the embryologically and physiologically related accessory
      male sex glands, other than the prostate. METHODS: The accessory male sex glands
      of Cowper, Littre, and Morgagni were studied systematically in 10 whole-mount
      autopsy and 5 surgical cystoprostatourethrectomy specimens. Immunohistochemistry
      was applied with the avidin-biotin-peroxidase method and commercially available
      monoclonal antibodies raised against prostate-specific antigen (PSA) and prostate
      specific acid phosphatase (PSAP). RESULTS: All specimens showed clear microscopic
      identification of these glands except for Cowper's glands, which were not found
      in most of the surgical cystoprostatourethrectomy specimens but were found
      coincidentally in one. Localization of the prostate-specific markers PSA and PSAP
      was demonstrated for the first time in three Cowper's glands, but they were a
      consistent finding in Littre's and Morgagni's glands when immunohistochemical
      identification was performed in a systematic fashion. CONCLUSIONS: PSA and PSAP
      are mostly produced by prostatic tissue, but not exclusively. These findings may
      have an impact on the specificity and sensitivity of PSA serum levels after
      radical prostatectomy because they support the hypothesis of extraprostatic
      sources of PSA.

PMID- 7518987
TI  - More than one component of the Newcastle disease virus particle is capable of
      interferon induction.
AB  - The interferon (IFN)-inducing capacities of intact NDV virions, beta
      propiolactone-inactivated particles and several structural components were
      compared, using human PBML as the IFN producing cells. Intact and inactivated
      virions as well as the nucleocapsid fraction did not differ significantly in
      their IFN-inducing capacity. In contrast, genomic RNA as well as M protein
      fraction and envelopes induced IFN titres to a level of about 10% of those
      achieved with virions. NDV-induced IFN production could be blocked specifically
      by incubation with polyclonal anti-NDV-monoclonal antibodies (mAbs) and with two
      of three anti-HN-mAbs, but not with anti-NDV-mAbs directed against the F, M or NP
      protein. In addition, IFN induction by fixed MDBK cells, expressing NDV surface
      proteins after infection with NDV Ulster, was inhibited by one of two anti-F
      mAbs. The results suggest that the induction of IFN synthesis in human PBML is a
      complex process involving not only the HN protein but also the uncleaved F
      protein precursor, a component of the M protein fraction and--once having entered
      the cell--the genomic RNA.

PMID- 7518988
TI  - Mycobacterium paratuberculosis and Escherichia coli share common antigenic
      determinants.
AB  - Paratuberculosis (Johne's disease) is a chronic enteritis of ruminants, which is
      due to infection by Mycobacterium paratuberculosis. By comparative analysis of
      Western blots of M. paratuberculosis components incubated with sera from
      paratuberculous cows (either pre-absorbed or not on an Escherichia coli
      sonicate), we have shown the presence of cross-reactive antigens between M.
      paratuberculosis and E. coli. Components in the range of 22 to 75 kDa are
      recognized by sera from paratuberculous cows, but only some components in the
      range of 20 to 40 kDa are endowed with specific B-cell epitopes to M.
      paratuberculosis with respect to E. coli. Cross-reactions were further stressed
      by the fact that rabbit immunoglobulins to E. coli recognized some ten M.
      paratuberculosis components (in the range of 45 to 66 kDa). The importance of
      cross-reactivity between the two bacterial species was evaluated by enzyme-linked
      immunosorbent assay (ELISA) using soluble sonic-extract components from M.
      paratuberculosis as antigens. Pre-absorption of series of bovine sera with E.
      coli resulted in the diminution of ELISA mean optical density readings by 16.1%
      and 62.0% for paratuberculous or healthy animals, respectively.

PMID- 7518989
TI  - Encapsulation of Streptococcus uberis: influence of storage and cultural
      conditions.
AB  - Streptococcus uberis (n = 100) isolated from bovine mammary secretions were
      assessed by India ink for expression of capsule. Organisms were evaluated under
      four conditions; (1) after primary culture on blood agar, (2) following 5
      passages on blood agar, (3) after 5 passages in Trypticase Soy Broth (TSB), and
      (4) after storage in 10% skim milk. Strains from primary culture (44 of 100) were
      positive for an unstained halo (capsule) by the India ink method. Number of
      strains expressing capsule decreased greatly after passage and following storage.
      Freeze-etching followed by electron microscopy confirmed results of India ink
      preparations. Strains were also cultured in various media to determine influence
      of medium components on capsule expression. Todd-Hewitt medium supplemented with
      either serum or egg yolk enhanced the size of capsule expressed. Results of this
      study may aid researchers investigating the pathogenicity of S. uberis.

PMID- 7518990
TI  - [The prevention of mental pathology at an early age].
AB  - New principles of family medical-psychological and psychotherapeutic correction
      of infants and their parents are presented. Main approaches to prevention of
      psychic disorders in early childhood are formulated and main tasks for different
      specialists are specified. Organizational structures such as primary preventive
      centers based on joint activities of physicians, psychologists and pedagogues are
      offered.

PMID- 7518991
TI  - [Cytokine production by MTSC 4 cells, an established mouse thymic dendritic cell
      line].
AB  - The cytokine production by MTSC 4 cells, a murine thymic dendritic cell line
      established in our laboratory, has been investigated. Without exogenous
      stimulation, the MTSC 4 cells constitutively produce multiple types of cytokines,
      including IL-1, IL-6, IL-7, CSF, IFN and Chemotactic factor (CF). Of which, IL-6
      and IFN were abundant: IL-1 and Chemokine, moderate: IL-7 and CSF at low level.
      MTSC4 cells could not produce detectable either IL-3 of TNF alpha. The
      establishment of MTSC 4 may be useful in the analysis of the mechanism of thymus
      selection, and in the study of the network regulation of autocrined cytokines.

PMID- 7518992
TI  - Diagnosis of premature rupture of the membranes by the identification of alpha
      feto-protein in vaginal secretions.
AB  - Premature rupture of membranes (PROM) is sometimes difficult to diagnose. This
      report proposes the use of alpha-feto-protein (AFP) values in vaginal secretions
      for diagnostic tests. Our investigation took place in two separate phases. The
      first phase validated the AFP test using an immuno-enzymatic assay method and
      determined a threshold value from a sample of 167 female patients (Group 1: 133
      patients with an extremely low probability of PROM, and Group 2: 54 patients with
      confirmed PROM). In the second phase the test was applied to a sample of 145
      female patients (Group 3) with suspected, but unconfirmed, PROM. Results from
      alpha-feto-protein (AFP) evaluation were compared with data obtained from
      clinical, echographic and other tests. The positive/negative threshold adopted
      was an AFP concentration of 30 micrograms/l. For the two first groups, 1 and 2,
      sensitivity and specificity was in the 98% to 99% confidence level. For Group 3,
      sensitivity and specificity results at the 30 micrograms/l threshold value were
      94.5% and 95.4% respectively. Quantitative measurement of AFP determined by
      immuno-enzymatic assay of vaginal secretions with a threshold of 30 micrograms/l
      is a reliable, simple and rapid diagnostic test. Results obtained are
      significantly better than the measurement of pH, the determination of prolactin,
      and more practical than diamino-oxidase (DAO) assays.

PMID- 7518993
TI  - Periosteal osteosarcoma and parosteal chondrosarcoma evaluated by double
      immunohistochemical staining. Report of 2 cases.
AB  - Differentiation of periosteal osteosarcoma and parosteal (periosteal)
      chondrosarcoma by conventional histology may be difficult. One case each of
      clinically and histologically proven periosteal osteosarcoma and parosteal
      chondrosarcoma were evaluated by a double-immunohistochemical staining method
      using proliferating cell nuclear antigen (PCNA) and S-100 protein (S-100).
      Conventional histology showed proliferation of both osteoblastic and
      chondroblastic cells in the periosteal osteosarcoma, while there was a growth of
      only chondroblastic tumor cells in the parosteal chondrosarcoma.
      Immunohistochemical studies indicated that the nuclei of chondroblastic cells
      recognized by S-100 were PCNA-negative, while osteoblastic stromal cells were
      PCNA-positive in the periosteal osteosarcoma. In contrast, chondroblastic cells
      in the parosteal chondrosarcoma were both S-100- and PCNA-positive. Our findings
      suggest that periosteal osteosarcoma is characterized by the proliferation of
      osteoblastic stromal cells, whereas parosteal chondrosarcoma is characterized by
      the proliferation of chondroblastic cells. This method of double
      immunohistochemical staining, using PCNA and S-100, may be useful in
      differentiating these chondroblastic tumors.

PMID- 7518994
TI  - Arteriovenous malformations that rupture during pregnancy: a management dilemma.
AB  - Intracranial haemorrhage due to rupture of an arteriovenous malformation (AVM)
      during pregnancy is a rare but serious condition that warrants prompt
      recognition. Once the diagnosis is made, the management is primarily based on
      neurosurgical rather than obstetric considerations. Due to its rarity, no
      definitive guidelines exist, and the best time to perform elective surgery (i.e.,
      at presentation or at completion of the pregnancy) is ill-defined. This report
      describes three patients recently treated at our institution who had AVMs that
      ruptured during pregnancy. These cases well summarize the difficulties
      encountered in treating such patients. The diagnostic as well as the therapeutic
      implications of this condition are discussed.

PMID- 7518996
TI  - Use of G-CSF in a patient with Hunter syndrome receiving bone marrow
      transplantation.

PMID- 7518995
TI  - Transplantation of allogeneic peripheral blood stem cells after myeloablative
      treatment of a patient in blastic crisis of chronic myelocytic leukemia.
AB  - A 48-year-old man in blastic crisis of chronic myelocytic leukemia received a
      transplant of allogeneic peripheral blood stem cells. The donor was his HLA
      identical sister, who refused to donate bone marrow cells, but agreed to donate
      peripheral blood stem cells. The patient received standard transplant
      conditioning with cyclophosphamide (120 mg/kg) and busulfan (16 mg/kg).
      Peripheral blood stem cells were mobilized with granulocyte colony stimulating
      factor and collected by apheresis. After transplantation, the white blood cell
      count and the result of microscopic analysis of the bone marrow became normal,
      and the leukocyte karyotype became 46XX. DNA fingerprinting showed complete
      chimerism. Graft-versus-host disease was suppressed with cyclosporine and methyl
      prednisolone. The patient died of recurrence of leukemia on day 102+.

PMID- 7518997
TI  - New antipsychotic agent, risperidone, introduced.

PMID- 7518998
TI  - Temporal and spatial localization of type I and II collagens in human thyroid
      cartilage.
AB  - Thyroid cartilages of various ages were investigated by immunofluorescence
      staining for localization of the fibrillar collagen types I and II in order to
      understand the tissue remodeling occurring during the mineralization and
      ossification of thyroid cartilage. In fetal and juvenile thyroid cartilages, type
      I collagen was restricted to the inner and outer perichondrium, while type II
      collagen was localized in the matrix of hyaline cartilage. However, in advanced
      ages, type I collagen was also localized in the pericellular and in the
      interterritorial matrix of intermediate and central chondrocytes of thyroid
      cartilage. The matrix of peripheral chondrocytes was negative for type I
      collagen. This suggest that some chondrocytes in thyroid cartilage undergo a
      differentiation to type I collagen-producing chondrocytes. At the beginning of
      ossification, bone-related type I collagen was chiefly detected in the central
      cartilage layer, but was never deposited first from the perichondrium in the
      direction to the subperichondrial cartilage. This observation confirmed previous
      findings showing that osteogenesis mainly follows an endochondral ossification
      pattern. Interterritorial matrix failed to react with the type II collagen
      antibody in men from the beginning of the third decade, and later still in women,
      even after treatment with hyaluronidase. These observations indicate that major
      matrix changes occur faster in male than in female thyroid cartilage.

PMID- 7519001
TI  - Iloprost availability.

PMID- 7519002
TI  - Synthetic polymeric inhibitors of influenza virus receptor-binding activity
      suppress virus replication.
AB  - A new approach to anti-influenza chemotherapy is based on the development of
      synthetic inhibitors of virus attachment to host cells. These inhibitors are
      prepared by anchoring the minimum receptor determinant of influenza virus, sialic
      acid, to polymeric or liposomal carriers. In this study, a series of poly(acrylic
      acid-co-acrylamides) and dextrans bearing pendant glycylamidobenzylsialoside
      groups were synthesized and evaluated for their binding to a panel of influenza A
      and B virus strains and for their ability to inhibit virus infectivity in cell
      culture. Significant type-, subtype-, and strain-specific variation in virus
      susceptibility to the synthetic inhibitors was observed. Among the viruses
      tested, H3 subtype strains evolved in humans since 1975 were the most sensitive,
      while the earlier H3 viruses and the type B strains were resistant. The virus
      inhibitory potency of the polymeric sialosides correlated with their bindings to
      the virus, and was dependent on the virus affinity for the ligand, the density of
      the ligand, and the nature and molecular mass of the polymeric carrier. In
      embryonated eggs, the antiviral effect of poly(acryloyl
      glycylamidobenzylsialoside-co-acrylic acid) was comparable to that of equine
      alpha 2-macroglobulin.

PMID- 7519000
TI  - Left ventricular mechanical consequences of dihydropyridine calcium channel
      modulation in conscious and anesthetized chronically instrumented dogs.
AB  - BACKGROUND: Volatile anesthetics depress left ventricular contractile function by
      altering voltage-dependent slow calcium (Ca2+) channel activity in the
      sarcolemmal membrane. This investigation examined the left ventricular systolic
      and diastolic mechanical effects of the dihydropyridine Ca2+ channel antagonist
      nifedipine and agonist Bay k 8644 (Bay k) in dogs in the conscious state and
      during anesthesia. METHODS: Forty-eight experiments were conducted using 16
      chronically instrumented dogs during autonomic nervous system blockade.
      Myocardial contractility was evaluated with the slope (Mw) of the regional
      preload recruitable stroke work relationship. Diastolic function was assessed
      using a time constant of isovolumic relaxation (tau), a regional chamber
      stiffness constant (Kp), and maximum segment lengthening velocity during rapid
      ventricular filling (dL/dtmax). On 3 separate days (24 experiments), a nifedipine
      infusion at 0.5, 1.0, 2.0, or 4.0 micrograms.kg-1.min-1 was administered.
      Hemodynamics and left ventricular pressure-segment length diagrams were recorded
      after a 10-min equilibration at each dose in the conscious state or during
      isoflurane or halothane anesthesia (0.8 MAC). In 24 parallel experiments, a Bay k
      infusion at 0.5, 1.0, 2.0, or 4.0 micrograms.kg-1.min-1 was administered, and
      hemodynamics and left ventricular function parameters were assessed after a 10
      min equilibration in the conscious state or during isoflurane or halothane
      administration (1.2 MAC). RESULTS: In conscious dogs, nifedipine significantly (P
      < 0.05) decreased Mw (71 +/- 5 to 42 +/- 4 mmHg during the high dose) and
      increased tau (35 +/- 1 to 48 +/- 3 ms during the high dose) without changes in
      dL/dtmax or Kp. In anesthetized dogs, nifedipine decreased Mw and dL/dtmax) (31
      +/- 4 during isoflurane to 27 +/- 3 mm/s during the high dose) and increased tau
      and Kp (0.43 +/- 0.05 during isoflurane to 0.53 +/- 0.04 mm-1 during the high
      dose). Administration of Bay k increased Mw, decreased tau, and increased
      dL/dtmax in conscious dogs. In contrast, no changes in tau were observed in dogs
      anesthetized with isoflurane or halothane during infusions of Bay k despite
      concomitant increases in Mw. Bay k also enhanced dL/dtmax and decreased Kp during
      isoflurane but not halothane anesthesia. CONCLUSIONS: Nifedipine caused direct
      negative inotropic actions in conscious and anesthetized dogs and worsened
      volatile anesthetic-induced negative lusitropic effects. Bay k improved left
      ventricular systolic and diastolic function in the conscious state. Bay k also
      improved contractility during anesthesia; however, Bay k only partially reversed
      volatile anesthetic-induced abnormalities in indexes of left ventricular
      diastolic function in dogs during autonomic nervous system blockade.

PMID- 7518999
TI  - Sperm decondensation and semen parameters: utilization of a simple staining
      technique for the evaluation of human sperm decondensation.
AB  - The ability of spermatozoa to fertilize an oocyte depends on a sequence of events
      ending ultimately in the decondensation of the sperm chromatin on penetration of
      the oocyte. Knowledge of what percentage of sperm decondenses is useful,
      especially in patients where other functional tests and sperm quality fail to
      explain the reported poor in vitro fertilization (IVF) rates. The objective of
      this study was (1) to compare sperm decondensation induced by either SDS/EDTA or
      heparin with semen parameters (volume, concentration, motility and morphology),
      and (2) to evaluate the use of a simplified staining technique (Diff QuikR [DQ])
      in comparison with the standard phase contrast method (Rose Bengal-[RB]).
      Randomly selected semen samples from 31 men attending an assisted reproductive
      programme were analysed for basic semen parameters and decondensation with
      SDS/EDTA and heparin. Two staining methods for the evaluation of decondensation
      were compared (phase contrast microscopy after Rose Bengal [RB] staining and
      light microscopy after Diff QuikR (DQ) staining). Moderate and grossly swollen
      sperm heads were recorded. Semen samples included both fertile and unfertile
      semen parameters. Sperm decondensation results showed poor to moderate
      correlations with semen parameters. The SDS/EDTA (DQ) (moderate forms) showed a
      significant negative correlation (r = -0.46) with seminal volume and a
      significant positive correlation (r = 0.41) with normal sperm morphology. The
      heparin (DQ) (moderate forms) decondensation showed a significant positive
      correlation with motility (r = 0.61) and sperm concentration (r = 0.43). The DQ
      method was preferred over the RB method due to its optical and storage
      advantage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519003
TI  - Development of a human immunodeficiency virus-1 in vitro DNA synthesis system to
      study reverse transcriptase inhibitors.
AB  - A Human immunodeficiency virus type-1 endogenous reverse transcriptase reaction
      was developed as an in vitro assay to study the inhibition of reverse
      transcription by antiviral compounds. Conditions were established for producing
      genomic length (-) strand DNA in high yields and measuring the inhibition of this
      transcript as the assay endpoint. In addition to genomic length (-) strand DNA, a
      novel segmented (-) strand product composed of a 6.0 kb reverse transcript of the
      5' 2/3 of the viral RNA genome and a 3.5 kb reverse transcript of the 3' 1/3 was
      observed. The most prominent (+) strand product was the size expected for plus
      strong stop DNA. Additional minor (+) strand species were also observed. The
      triphosphate form of the nucleoside analog inhibitor 3'-azido-3'-deoxythymidine
      (RETROVIR, Zidovudine, AZT) and BI-RG-587 (nevirapine), a non nucleoside
      inhibitor, were used to demonstrate the utility of the endogenous system for the
      analysis of reverse transcriptase inhibitors. In a standard reaction, synthesis
      of genomic length DNA was 50% inhibited by 0.1 microM AZTTP and 0.1 microM
      nevirapine.

PMID- 7519004
TI  - Bulbospinal neurons of the cat that co-contain serotonin and methionine
      enkephalin.
AB  - The present study utilizes a combined retrograde transport of Fast Blue (or
      rhodamine-labeled latex microspheres) and simultaneous immunofluorescence
      technique to demonstrate directly the coexistence of serotonin and methionine
      enkephalin in bulbospinal neurons of the cat. The bulbospinal neurons that
      immunostained for both serotonin and enkephalin were observed, without any
      distinct somatotopic organization, in the nuclei raphe pallidus, obscurus and
      magnus. They were also observed in the nucleus reticularis magnocellularis and
      the ventrolateral medulla (cell group B1/3). Among the bulbospinal neurons
      encountered within individual 5-HT-rich medullary nuclei, high proportions of
      these neurons co-containing serotonin and methionine enkephalin were evidenced in
      the nucleus raphe obscurus (64%) and nucleus raphe pallidus (56%), less so in
      cell group B1/3 (41%), nucleus raphe magnus (39%), and the nucleus reticularis
      magnocellularis (29%). Physiological significance of such a morphological
      substrate is discussed.

PMID- 7519005
TI  - High-dose selegiline in treatment-resistant older depressive patients.
AB  - BACKGROUND: We examined the effect of high-dose selegiline in 16 treatment
      resistant older depressive patients. We hypothesized that selegiline, at a dosage
      of 60 mg/d, would be at least partially effective but that the higher doses would
      not maintain the monoamine oxidase B selectivity observed with the lower doses of
      selegiline. METHODS: Sixteen treatment-resistant subjects (mean [+/- SD] age,
      65.6 +/- 9.3 years) entered a double-blind, randomized, crossover study of
      placebo vs 3 weeks of selegiline at a dosage of 60 mg/d. Objective measures of
      mood and behavior were obtained in all subjects, and 10 of the subjects underwent
      repeated lumbar punctures for analysis of monoamine metabolites in the
      cerebrospinal fluid. RESULTS: Objective measures of mood and behavior revealed
      significant improvement in the Hamilton Depression Rating Scale score (37.4%
      decrease), the Global Depression score (22.7% decrease), and the Brief
      Psychiatric Rating Scale score (19.3% decrease); subjective behavioral measures,
      however, did not show significant improvement during the 3-week medication trial.
      Cerebrospinal fluid values revealed a statistically significant drop in 3-methoxy
      4-hydroxyphenylglycol (51%) and 5-hydroxyindoleacetic acid (17%) levels, and
      there was a significant lowering of systolic blood pressure on standing (15%),
      but these changes were not accompanied by clinical side effects. CONCLUSIONS: Our
      results suggest that high-dose selegiline can be an effective antidepressant in
      treatment-resistant older depressive patients. While the selegiline dose required
      has nonselective monoamine oxidase effects and thus would not be free of possible
      tyramine interactions, other advantages suggest that further investigations with
      selegiline are warranted in this population.

PMID- 7519006
TI  - Uptake of nitric oxide synthase inhibitors by macrophage RAW 264.7 cells.
AB  - Uptake of the nitric oxide synthase inhibitors NG-methyl-L-arginine (L-NMA) and
      NG-nitro-L-arginine (L-NNA) by macrophages is mediated by two different
      mechanisms. Activation of the cells with cytokines resulted in an up-regulation
      of L-NMA uptake but did not affect L-NNA transport. Characterization of the
      transport sites revealed that uptake of L-NMA is mediated by a cationic amino
      acid transporter (system y+) whereas a neutral amino acid transporter (system L)
      accounts for the uptake of L-NNA.

PMID- 7519007
TI  - Lymphocytes possess an electrogenic H(+)-transporting pathway in their plasma
      membrane.
AB  - The existence of an electrogenic H(+)-transporting pathway similar to that
      described in the plasma membrane of granulocytes and macrophages is reported in
      pig peripheral lymphocytes. The function of the H(+)-transport pathway can only
      be detected when free movement of charge-compensating cations is allowed. H+
      transport is stimulated by arachidonic acid and various unsaturated fatty acids,
      and inhibited by bivalent cations, with the following sequence of efficiency:
      Zn2+ > Cd2+ = Co2+ = Ni2+ > Mn2+ > Ba2+ = Ca2+ = Mg2+. The transport pathway is
      activated by intracellular acidification and by NN'-dicyclohexylcarbodiimide, but
      it is not influenced by phorbol 12-myristate 13-acetate. As pig peripheral
      lymphocytes are not able to produce O2-., it is suggested that the operation of
      the electrogenic H+ conductance does not require the assembly of a functional
      NADPH oxidase.

PMID- 7519008
TI  - Purines induce lipofuscin formation in a colon carcinoma cell line.
AB  - Lipofuscin was produced when HT29, a colon carcinoma cell line, was cultured in
      millimolar concentrations of xanthine and guanine but not in the presence of
      other bases. Using a simple assay developed to quantify the fluorescent pigment,
      it was found that maximum levels of lipofuscin were developed in 3 days.
      Methylxanthines that are not substrates of xanthine dehydrogenase, such as
      caffeine and theophylline, did not induce formation of lipofuscin. Xanthine
      induced lipofuscin formation could be inhibited by oxypurinol, indicating that
      the pigment may be formed by free radicals generated by xanthine dehydrogenase.
      It is suggested that the lipofuscin seen in pseudomelanosis coli may result from
      the accumulation of purines in the colon.

PMID- 7519009
TI  - Regulation of System B0 amino-acid-transport activity in the renal epithelial
      cell line NBL-1 and concomitant changes in SAAT1 hybridizing transcripts.
AB  - alpha-(Methylamino)isobutyric acid (MeAIB) insensitive Na(+)-dependent alanine
      transport activity in the bovine kidney cell line NBL-1 was increased upon amino
      acid starvation (> or = 20% over control levels). When L-phenylalanine (3 mM) was
      included in the starvation medium the increase was further enhanced (> or = 85%
      over control levels). In cells grown in control medium the Vmax, for MeAIB
      insensitive Na+/alanine co-transport was found to be 6.0 +/- 0.7 nmol/3 min per
      mg (Km 41 +/- 12 microM) and for L-phenylalanine-treated amino-acid-starved cells
      the Vmax. was 21 +/- 5 nmol/3 min per mg (Km 92 +/- 40 microM). The increase in
      Vmax. was prevented by cycloheximide. Substrate specificity analysis identified
      the L-phenylalanine-induced transport system as System B0. [35S]Methionine
      labelling of cells during the amino acid starvation/phenylalanine treatments
      resulted in the differential labelling of a protein of 78 kDa. Northern-blot
      analysis using a SAAT1-specific probe revealed the presence of a new transcript
      (3.2 kb) in RNA extracted from cells incubated in amino acid starvation medium
      with L-phenylalanine included. The present findings suggest a novel means of
      control for System B0 by the use of physiological stress. It is also proposed
      that SAAT1 and System-B0 transcripts have considerable sequence similarity.

PMID- 7519010
TI  - Regulation of endothelin-1- and lysophosphatidic acid-stimulated tyrosine
      phosphorylation of focal adhesion kinase (pp125fak) in Rat-1 fibroblasts.
AB  - The characteristics of protein tyrosine phosphorylation were examined in Rat-1
      fibroblasts in response to endothelin-1 (ET-1) and 1-oleoyl-lysophosphatidic acid
      (LPA). Both agonists stimulated the biphasic tyrosine phosphorylation of at least
      three major proteins of approx. 120 kDa (pp116, pp120 and pp130) and two of 80
      kDa (pp80 and pp70). Immunoprecipitation experiments indicated that the pp120
      protein corresponded to the recently described focal adhesion protein kinase
      pp125fak. Phorbol 12-myristate 13-acetate, alone or in combination with the
      calcium ionophore A23187, also stimulated the phosphorylation of pp125fak but to
      a smaller extent than LPA or ET-1. Removal of both extracellular and
      intracellular Ca2+ did not significantly reduce LPA- and ET-1-stimulated tyrosine
      phosphorylation of pp125fak. In cells where protein kinase C activity was down
      regulated or inhibited, ET-1-stimulated tyrosine phosphorylation of pp125fak was
      reduced to a greater extent than phosphorylation in response to LPA. In addition,
      ET-1-stimulated tyrosine phosphorylation of pp80 was decreased by 50-70% in
      response to protein kinase C inhibition at both 2 and 60 min whereas LPA
      stimulated tyrosine phosphorylation of this protein was only reduced at 2 min.
      Pretreatment with pertussis toxin reduced the tyrosine phosphorylation of pp42
      and pp44 forms of mitogen-activated protein kinase in response to both ET-1 and
      LPA but reduced the tyrosine phosphorylation of pp125fak only in response to LPA.
      These results indicate agonist-specific differences in the regulation of pathways
      mediating the tyrosine phosphorylation of pp125fak and other target proteins.

PMID- 7519013
TI  - The action of the DNA intercalating agents 4'-(9-acridinylamino) methanesulphon-m
      anisidide and 1,4-bis(butylamino) benzo[g]phthalazine in U-937 human promonocytic
      cells: relationship between cell cycle and differentiation.
AB  - The action of two structurally related DNA intercalating agents has been studied
      and compared, namely 4'-(9-acridinylamino) methanesulphon-m-anisidide (amsacrine,
      mAMSA) and 1,4-bis(butylamino)benzo[g]phthalazine (ABP) on the cell cycle and
      differentiation of U-937 human promonocytic leukemia cells. mAMSA (0.1 microM)
      and ABP (4 microM) reduced the proliferation activity to a similar extent and
      caused little cell mortality. At these subcytotoxic concentrations mAMSA induced
      the cells to accumulate at the G2 phase of the cycle, while cycle inhibition
      provoked by ABP was not phase specific. In addition, mAMSA caused an increase in
      the cell mass while ABP provoked cell shrinkage. This was consistent with the
      fact that ABP considerably inhibited protein synthesis, while mAMSA did not
      significantly affect this activity. SDS/K+DNA precipitation assays indicated that
      mAMSA, but not ABP, stimulated protein-DNA covalent complex formation. Finally,
      it was found that mAMSA, but not ABP, elicited the expression of differentiation
      markers, namely nitroblue tetrazolium reduction, activation of vimentin and
      leukocyte integrin (CD11b/CD18 and CD11c/CD18) expression, and downregulation of
      c-myc expression. The DNA intercalators doxorubicin and mitoxantrone, which like
      mAMSA induced the cells to accumulate at the G2 phase and increased the cell
      mass, induced the expression of differentiation markers. In contrast, the
      intercalators aclarubicin and caffeine and the non-intercalator novobiocin, which
      produced minor alterations on cell-cycle distribution and caused cell shrinkage,
      did not significantly elicit differentiation. These results support the
      conclusion that differentiation of myeloid leukemia cells by cytostatic drugs
      depends on the perturbations of the cell cycle, leading to disproportionate
      increases in cell mass.

PMID- 7519011
TI  - Maitotoxin activates cation channels distinct from the receptor-activated non
      selective cation channels of HL-60 cells.
AB  - We investigated whether maitotoxin activates non-selective cation channels, as
      was recently proposed [Soergel, Yasumoto, Daly and Gusovsky (1992) Mol.
      Pharmacol. 41, 487-493]. Stimulation of dibutyryl cyclic AMP-differentiated HL-60
      cells with the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine
      (fMLP; 0.1 microM), the Ca(2+)-ATPase inhibitor thapsigargin (0.1 microM) or
      maitotoxin (25 ng/ml) resulted in an increase in cytoplasmic free calcium
      concentration ([Ca2+]i). Unlike fMLP and thapsigargin, maitotoxin produced no
      increase in [Ca2+]i in the absence of extracellular Ca2+. The increase in [Ca2+]i
      induced by fMLP was blocked by pretreatment with pertussis toxin (100 ng/ml for
      24 h) but not that induced by maitotoxin. Similarly, the increase in [Ca2+]i
      produced by fMLP but not that produced by maitotoxin was inhibited by
      pretreatment with phorbol myristate acetate (100 ng/ml). Both fMLP- and
      maitotoxin-induced increases in [Ca2+]i were blocked by 1-(beta-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenylethyl)-1H-imid azole hydrochloride (SKF
      96365) in a concentration-dependent manner. However, the maitotoxin-induced
      increase in [Ca2+]i was more sensitive to inhibition by SKF 96365 than the fMLP
      induced increase. fMLP-induced increases in [Ca2+]i were blocked by cations with
      Gd3+ being more effective than Cd2+, whereas for maitotoxin Cd2+ was more
      effective than Gd3+. Both fMLP and thapsigargin stimulated quenching of Fura-2
      fluorescence in the presence of extracellular Mn2+, whereas maitotoxin produced
      no Mn2+ quenching. Taken together these results suggest that maitotoxin does not
      stimulate the nonselective cation channel activated by fMLP, but instead
      activates Ca2+ influx by a different mechanism.

PMID- 7519014
TI  - Entrapment of cisplatin into biodegradable polyalkylcyanoacrylate nanoparticles.
AB  - The entrapment of cisplatin into biodegradable colloidal systems
      (polyalkylcyanoacrylates) was studied. Nanoparticles were characterized in terms
      of relevant parameters for organ distribution in vivo, such as particle diameter
      and particle size distribution, determined by correlation photon spectroscopy and
      transmission electron microscopy. Association efficiency was also evaluated by
      Plasma Emission Spectrophotometry. The ability of surfactants (sodium lauryl
      sulphate and poloxamer 188), and dextrans of various molecular weights, to
      improve the binding of the drug to polyalkylcyanoacrylates was also studied. The
      dextran content in nanoparticles, as determined by polarimetry, increases with
      the molecular weight of the polysaccharide. The highest value of association
      efficiency of cisplatin to nanoparticles was obtained in the presence of dextran
      70 with sodium lauryl sulphate (0.08%) as stabiliser.

PMID- 7519012
TI  - Conversion of secretory proteins into membrane proteins by fusing with a
      glycosylphosphatidylinositol anchor signal of alkaline phosphatase.
AB  - Placental alkaline phosphatase (PLAP) is initially synthesized as a precursor
      (proPLAP) with a C-terminal extension. We constructed a recombinant cDNA which
      encodes a chimeric protein (alpha GL-PLAP) comprising rat alpha 2u-globulin
      (alpha GL) and the C-terminal extension of PLAP. Two molecular species (25 kDa
      and 22 kDa) were expressed in the COS-1 cell transfected with the cDNA for alpha
      GL-PLAP. Only the 22 kDa form was labelled with both [3H]stearic acid and
      [3H]ethanolamine. Upon digestion with phosphatidylinositol-specific phospholipase
      C the 22 kDa form was released into the medium, indicating that this form is
      anchored on the cell surface via glycosylphosphatidylinositol (GPI). A specific
      IgG raised against a C-terminal nonapeptide of proPLAP precipitated the 25 kDa
      form but not the 22 kDa form, suggesting that the 25 kDa form is a precursor
      retaining the C-terminal propeptide. When a mutant alpha GL-PLAP, in which the
      aspartic acid residue is replaced with tryptophan at a putative
      cleavage/attachment site, was expressed in COS-1 cells, the 25 kDa precursor was
      the only form found inside the cell and retained in the endoplasmic reticulum, as
      judged by immunofluorescence microscopy. In vitro translation programmed with
      mRNAs coding for the wild-type and mutant forms of alpha GL-PLAP demonstrated
      that the C-terminal propeptide was cleaved from the wild-type chimeric protein,
      but not from the mutant one. This gave rise to the 22 kDa form attached with a
      GPI anchor, suggesting that GPI is covalently linked to the aspartic acid residue
      (Asp159) of alpha GL-PLAP. Taken together, these results indicate that the C
      terminal propeptide of PLAP functions as a signal to render alpha GL a GPI-linked
      membrane protein in vitro and in vivo in cultured cells, and that the chimeric
      protein constructed in this study may be useful for elucidating the mechanism
      underlying the cleavage of the propeptide and attachment of GPI, which occur in
      the endoplasmic reticulum.

PMID- 7519015
TI  - A new perspective on the nature of the cancer problem: anti-cellular senescence.

PMID- 7519016
TI  - Positive and negative regulations of albumin gene expression by retinoids in
      human hepatoma cell lines.
AB  - All-trans-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (designated
      "acyclic retinoid") induced upregulation of the albumin gene expression at its
      transcriptional level, whereas all-trans-retinoic acid (RA) induced
      downregulation of the expression in both PLC/PRF/5 and HuH7 human hepatoma cell
      lines. These up- and down regulations of the albumin gene expression coordinated
      with high and low levels of mRNA for hepatocyte nuclear factor-1 (HNF-1), which
      is one of the most potent transcription factors for the albumin gene, implying
      that retinoids may regulate albumin gene expression through HNF-1 expression in
      opposite ways. The PLC/PRF/5 and HuH7 hepatoma cell lines expressed retinoid X
      receptor-alpha (RXR alpha) mRNA, whose expression was constitutive. Acyclic
      retinoid and all-trans-RA both induced upregulation of retinoic acid receptor
      beta (RAR beta), and both suppressed cell proliferation-related phenotypic
      expressions by the alpha-fetoprotein gene and the c-myc oncogene. 9-cis-RA, whose
      receptor is known to be RXR alpha, also induced upregulation of albumin and HNF-1
      expression. These results suggest that acyclic retinoid may act through both RXR
      alpha and RAR beta, whereas all-trans-RA conveys only RAR beta-mediated
      functions, at least in these two hepatoma cell lines.

PMID- 7519017
TI  - [Palliative care as ultimate alternative. 'Palliative care also for the aged'.
      NVKVV dept. Brussels, Louvain, Tienen, 1 March 1994, Brussels].

PMID- 7519018
TI  - Systemic treatment of Kaposi's sarcoma: current status and future directions.

PMID- 7519019
TI  - Evaluation of monoclonal antibodies to HIV-1 envelope by neutralization and
      binding assays: an international collaboration.
AB  - OBJECTIVE: To characterize a purified panel of monoclonal antibodies (MAb) to
      epitopes in HIV-1 envelope V3, CD4-binding region, C4 and gp41. DESIGN:
      Neutralization and/or binding activity data were obtained from 21 laboratories on
      a coded panel consisting of seven human MAb, seven mouse MAb, recombinant human
      CD4 immunoadhesin [CD4-immunoglobulin G (IgG)], normal human and normal murine
      Ig. METHODS: Laboratories performed a variety of neutralization assays and
      antigen binding assays with HIVIIIB, HIVMN and other laboratory strains of HIV-1.
      RESULTS: For a single MAb, there was up to a 10(3) range of neutralizing antibody
      titers between laboratories. The range in titers appeared to depend on the
      sensitivity of the neutralization assay. Two methods were used to consolidate the
      data from all laboratories, the geometric mean titer (GMT) and the median
      neutralizing titer (MNT). The panel of MAb were also analyzed by a variety of
      assays that measure binding activity to native or denatured epitopes. The
      relative binding activity of the MAb did not appear to correlate with
      neutralizing activity. CONCLUSION: Neutralization results from any single
      laboratory did not correlate with the collective data. The relative potency (rank
      order) of the MAb in the panel were equivalent when determined by GMT or MNT.
      These values may be useful to individual laboratories for estimating the
      sensitivity of their neutralization assays. The study also identified potential
      reference reagents with which neutralizing activity could be compared.

PMID- 7519020
TI  - In vitro effects of stem-cell factor or interleukin-3 on myelosuppression
      associated with AIDS.
AB  - OBJECTIVE: To determine whether the early-acting hematopoietic growth factors
      stem-cell factor (SCF) or interleukin-3 (IL-3), are able to overcome the bone
      marrow suppressive effects of cytokines or drugs involved in the hematologic
      abnormalities that accompany HIV-1 infection. DESIGN: In vitro colony formation
      assays of normal human bone-marrow cells exposed to the myelosuppressive drugs,
      zidovudine, interferon-alpha (IFN-alpha) and ganciclovir, or the myelosuppressive
      cytokines, tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor
      beta (TGF-beta), implicated in HIV dysmyelopoiesis. RESULTS: SCF (10 ng/ml)
      enhanced the numbers of erythroid (BFU-E) colonies in the presence of zidovudine
      or ganciclovir (P < 0.05) and myeloid [colony-forming unit granulocyte macrophage
      (CFU-GM)] colonies in the presence of ganciclovir or IFN-alpha (P < 0.05)
      relative to controls. IL-3 (10 ng/ml) also improved erythroid colony numbers in
      the presence of zidovudine (P < 0.05) and CFU-GM in the presence of IFN-alpha (P
      < 0.05). Neither factor consistently altered the inhibition of TGF-beta or TNF
      alpha. The 50% inhibitory concentration (IC50) of the myelosuppressive agents was
      altered in only one setting, using IL-3 in the presence of zidovudine.
      CONCLUSIONS: These data suggest that SCF or IL-3 may have a therapeutic
      application in overcoming hematopoietic abnormalities associated with drugs
      commonly used in the care of AIDS patients. However, they may have less capacity
      to overcome the bone-marrow inhibitory effects of the endogenous cytokines TNF
      alpha and TGF-beta.

PMID- 7519021
TI  - Absence of evidence of retroviral infection in idiopathic CD4+ T-lymphocytopenia
      syndrome.

PMID- 7519022
TI  - High-level expression of functional glutamate receptor channels in insect cells.
AB  - We have expressed glutamate-gated ion channels in Spodoptera frugiperda Sf21
      insect cells using a recombinant baculovirus system. Cells infected with
      recombinant baculoviruses encoding the alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA)-selective glutamate receptor channel subunits GluR-B and GluR-D
      displayed specific high-affinity [3H]AMPA binding (apparent dissociation constant
      Kd of 15 nM for GluR-B and 40 nM for GluR-D) with pharmacological profiles
      typical of AMPA receptors. The binding reached maximal levels (Bmax of 15-30 pmol
      per mg of membrane protein) by 3-4 days postinfection. AMPA, glutamate and
      kainate triggered inward currents in GluR expressing cells, indicating assembly
      of functional homomeric channels. Formation of heteromeric GluR-B/D channels in
      doubly-infected cells was evident from the diagnostic current-voltage relations
      of AMPA-activated whole-cell currents. For the solubilization of the receptor,
      nonionic detergents Triton X-100, n-octyl-D-glucoside and n-dodecylmaltoside
      proved most effective. Detergent-solubilized receptor preparations were stable,
      retained their characteristic ligand-binding properties and bound to immobilized
      wheat germ lectin, demonstrating the glycosylation of insect cell-expressed GluR
      subunits. The expression level of 300-400 micrograms of receptor protein per
      liter of suspension culture should facilitate production of glutamate receptors
      for biochemical and structural studies.

PMID- 7519023
TI  - Selective RNA editing and subunit assembly of native glutamate receptors.
AB  - RNA editing and subunit assembly of ionotropic glutamate receptors (GluRs) were
      examined in an oligodendrocyte progenitor cell line, CG4, which expresses GluR2
      GluR4, GluR6, GluR7, KA1, and KA2. AMPA-evoked currents rapidly desensitize,
      whereas kainate-evoked currents contain a steady-state component with a nearly
      linear current-voltage relation and a fast desensitizing component that is
      inwardly rectifying. The Q/R site is edited > 95% to the arginine codon in
      GluR2(Q607) mRNA, and < 5% in GluR6(Q621) mRNA. Immunoprecipitation experiments
      demonstrate that GluR6 and/or GluR7 subunits assemble with KA2, but not with
      GluR2-GluR4. These results indicate that oligodendrocyte progenitor cells
      selectively edit and assemble glutamate receptors into at least two functionally
      and structurally distinct heteromeric channels.

PMID- 7519024
TI  - Opioid inhibition of Ih via adenylyl cyclase.
AB  - Opioids are coupled through G proteins to both ion channels and adenylyl cyclase.
      This study describes opioid modulation of the voltage-dependent cation channel,
      Ih, in cultured guinea pig nodose ganglion neurons. Forskolin, PGE2, and cAMP
      analogs shifted the voltage dependence of activation of Ih to more depolarized
      potentials and increased the inward current at -60 mV. Opioids had no effect on
      Ih alone, but reversed the effect of forskolin on Ih. This action of opioids was
      blocked by naloxone. Opioids had no effect on Ih in the presence of cAMP analogs,
      suggesting that modulation occurs at the level of adenylyl cyclase. The shift in
      the voltage dependence of Ih by agents that induce inflammation (i.e., PGE2) is
      one potential mechanism to mediate an increased excitability. Opioid inhibition
      of adenylyl cyclase and subsequent inhibition of Ih may be a mechanism by which
      opioids inhibit primary afferent excitability and relieve pain.

PMID- 7519025
TI  - Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR
      reduces NGF binding to TrkA on PC12 cells.
AB  - The role of the low affinity neurotrophin receptor, p75LNTR, in NGF-mediated
      signal transduction has been examined. Our results show that treatment of PC12
      cells with MC192, a monoclonal antibody directed against p75LNTR, results in
      reduced NGF binding to TrkA and attenuated TrkA activation. Use of mutant NGF
      that binds TrkA but not p75LNTR shows that the MC192 effect requires that NGF
      bind the p75LNTR receptor. To explore the possibility that MC192 disrupts some
      normal functional role of p75LNTR, BDNF was used to block binding of NGF to
      p75LNTR on PC12 cells. By preventing NGF binding to p75LNTR, NGF binding to TrkA
      and NGF-mediated signal transduction were reduced. We propose that p75LNTR
      normally acts to increase binding of NGF to TrkA, possibly by increasing the
      local NGF concentration in the microenvironment surrounding the cell surface TrkA
      receptor.

PMID- 7519026
TI  - Mice deficient for the myelin-associated glycoprotein show subtle abnormalities
      in myelin.
AB  - Using homologous recombination in embryonic stem cells, we have generated mice
      with a null mutation in the gene encoding the myelin-associated glycoprotein
      (MAG), a recognition molecule implicated in myelin formation. MAG-deficient mice
      appeared normal in motor coordination and spatial learning tasks. Normal myelin
      structure and nerve conduction in the PNS, with N-CAM overexpression at sites
      normally expressing MAG, suggested compensatory mechanisms. In the CNS, the onset
      of myelination was delayed, and subtle morphological abnormalities were detected
      in that the content of oligodendrocyte cytoplasm at the inner aspect of most
      myelin sheaths was reduced and that some axons were surrounded by two or more
      myelin sheaths. These observations suggest that MAG participates in the formation
      of the periaxonal cytoplasmic collar of oligodendrocytes and in the recognition
      between oligodendrocyte processes and axons.

PMID- 7519028
TI  - Identification of the linkage of mutations causing cystic fibrosis to different
      alleles of a tetranucleotide repeat in intron 6a of the CFTR gene.
AB  - The linkage of the intragenic polymorphic (GATT)n repeat to a number of cystic
      fibrosis transmembrane conductance regulator gene mutations (delta F-508, G542X,
      G551D, R553X, R1162X, W1282X, N1303K, R334W, and R347P) was studied. The linkage
      of delta F-508, G542X, and N1303K to a six-copy allele and of R334W to a seven
      copy allele of the repeat was found.

PMID- 7519027
TI  - Hexose metabolism in pancreatic islets: glycogen synthase and glycogen
      phosphorylase activities.
AB  - The activity of glycogen synthase and glycogen phosphorylase was measured in rat
      pancreatic islet homogenates. For this purpose, the sensitivity of current
      radioisotopic procedures for the assay of these enzymes in liver extracts was
      increased by about two orders of magnitude. Even so, the measurement of glycogen
      synthase and phosphorylase in islet homogenates was hampered by a potent amylase
      like activity, resulting in the hydrolysis of preformed or newly formed 14C
      labeled glycogen. Acarbose suppressed the latter phenomenon which was found
      attributable to both minute contamination of isolated islets by acinar cells and
      genuine alpha-amylase activity in purified islet beta-cells. As measured by the
      more sensitive method in the presence of acarbose, the a/(a+b) ratio for glycogen
      synthase activity in islet homogenates was increased in islets preincubated in
      the presence as distinct from absence of D-glucose and decreased after
      preincubation with forskolin. These changes represented a mirror image of those
      evoked by D-glucose and forskolin in the a/(a+b) ratio for glycogen phosphorylase
      activity. It is concluded that glycogen synthesis and breakdown are regulated in
      the endocrine pancreas in a manner qualitatively comparable to that prevailing in
      hepatocytes, the possible participation of an amylase-like activity to glycogen
      metabolism in intact islet beta-cells requiring further investigation.

PMID- 7519029
TI  - Functional health patterns: a curricular course model for adult acute care.
AB  - The Functional Health Pattern (FHP) model is a categorization of 11 areas that
      assist in diagnosing human responses to illness and identifying risk factors for
      dysfunctional health. The incorporation of this model as a content organizer in a
      beginning medical-surgical course in a baccalaureate curriculum is presented as
      an effective method of familiarizing students with the application of the nursing
      process. This model permits the student nurse to identify FHPs (client strengths)
      and dysfunctional patterns (nursing diagnoses).

PMID- 7519030
TI  - Antigen-presenting capacity in normal human dermis is mainly subserved by CD1a+
      cells.
AB  - A proposed role for antigen-presenting dermal dendrocytes in the pathogenesis of
      many dermal inflammatory skin diseases remains speculative. We therefore sought
      to determine the phenotype and functional characteristics of antigen-presenting
      cells isolated from normal human dermis. Normal adult human skin was incubated
      overnight with dispase at 4 degrees C, the epidermis was removed, and the
      residual dermal preparation was then minced and digested with a mixture of
      hyaluronidase, collagenase, and DNAase at 37 degrees C, prior to filtration
      through mesh. Dermal cell suspensions thus obtained were stained using specific
      monoclonal antibodies, and analysed by fluorescence microscopy or flow cytometry.
      Mean values were as follows: CD45+ leucocytes 39%, HLA-DR+ cells 39%, Ulex
      europaeus agglutinin I+ endothelial cells 26%, CD1a+ cells 3.9%, CD11b+ cells
      16%, CD11c+ cells 6%. Mitomycin C-treated crude dermal cell suspensions induced
      allostimulation of peripheral blood mononuclear cells in a 7-day culture, as
      assessed by 3H-TdR incorporation. Depletion of CD1a+ Langerhans-like cells from
      the dermal cell preparation, by 95, 74 and 90% in three separate experiments
      using immunomagnetic beads, reduced 3H-TdR incorporation at optimal responder-to
      stimulator cell ratios by 90, 64, and 87%, respectively. Our findings suggest
      that, in normal human dermis, the great majority of the alloantigen-presenting
      capacity resides in the CD1a+ Langerhans cell-like dendritic antigen-presenting
      cell population, and not to any great extent in either CD1a- macrophage-like
      cells, or HLA-DR+ endothelial cells. The relationship of the CD1a+ dermal antigen
      presenting cells to the Langerhans cell lineage remains to be determined.

PMID- 7519031
TI  - Cantharidin-induced acantholysis in Darier's disease: does acantholysis initiate
      dyskeratosis?
AB  - We have examined the action of cantharidin on the skin of patients with Darier's
      disease, and used immunohistological techniques to determine the distribution of
      desmosomal components, keratin intermediate filaments, and proteases in
      cantharidin-induced blisters. Cantharidin induced acantholysis, but the presence
      of acantholysis did not trigger the development of the characteristic warty,
      dyskeratotic papules in patients with Darier's disease. The distribution of
      desmosomal components, keratins and proteases within the acantholytic
      keratinocytes in the cantharidin-induced blisters was similar to that previously
      found in acantholytic cells within lesions of Darier's disease: peripheral
      staining for extracellular desmosomal components was reduced; some desmosomal
      components were detected diffusely in the acantholytic cells; basal cell keratin
      markers were expressed by some suprabasal acantholytic cells, and plasminogen was
      detected in association with acantholytic cells. Cleavage of desmosomes did not
      reveal the underlying abnormality in Darier's disease.

PMID- 7519032
TI  - The effect of tacalcitol (1,24(OH)2D3) on cutaneous inflammation, epidermal
      proliferation and keratinization in psoriasis: a placebo-controlled, double-blind
      study.
AB  - The aim of the present study was to discover to what extent 1,24(OH)2D3 ointment
      (tacalcitol; 4 micrograms/g) can modulate epidermal proliferation and
      keratinization, and several aspects of inflammation. Ten patients with psoriasis
      vulgaris were included in a placebo-controlled, double-blind study, using
      1,24(OH)2D3 ointment (4 micrograms/g). Before, and after 8 weeks of treatment,
      punch biopsies were taken from lesions treated with the active agent and placebo
      treated lesions. An immunohistochemical study was carried out using monoclonal
      antibodies against the hyperproliferation-associated keratin 16, against cycling
      nuclei, filaggrin, involucrin, T lymphocytes, Langerhans cells, CD14 and
      polymorphonuclear leucocytes (PMN). The Wilcoxon test for matched pairs was used
      for statistical analysis of results. The biopsies from the lesions treated with
      the active agent showed a statistically significant change towards normalization
      of all aspects of inflammation studied, and of epidermal proliferation and
      keratinization, but there did not appear to be any effect on Langerhans cells.
      The only parameter which showed a significant alteration in the placebo-treated
      lesions was the number of cycling nuclei in the epidermis (P < or = 0.02).
      However, the biopsies from the plaques treated with the active agent showed a
      greater decrease of cycling cells (decrease: Mactive = 70, Mplacebo = 53) and a
      lower P-value (< or = 0.01). We therefore conclude that at the cell biological
      level 1,24(OH)2D3 ointment (4 micrograms/g) has a substantial effect on several
      cell types, with regard to inflammation, epidermal proliferation and
      keratinization, with the exception of Langerhans cells.

PMID- 7519033
TI  - Localization of transforming growth factor-alpha RNA and protein in the skin of
      psoriatic patients receiving therapy.
AB  - Fourteen patients with chronic plaque psoriasis requiring in-patient therapy were
      treated with a variety of antipsoriatic agents. All had four skin biopsies taken:
      two prior to therapy, one from a psoriatic plaque and one from adjacent
      clinically normal skin, and two further biopsies, one 2-3 weeks after starting
      therapy, and one at clinical clearance, taken from an area where there was
      previously a psoriatic plaque. In addition, three biopsies were taken from
      clinically normal skin of non-psoriatics. Transforming growth factor-alpha (TGF
      alpha) RNA and protein distributions were estimated in these biopsies, using in
      situ hybridization with a cRNA TGF-alpha probe, and an antibody to TGF-alpha
      polypeptide. Prior to therapy, grain counts showed elevated levels of TGF-alpha
      RNA in the subcorneal layers of the epidermis. These levels decreased during
      clearance of the psoriasis. In one patient whose plaques did not clear, there was
      no decrease of TGF-alpha mRNA. Antibody studies showed the presence of TGF-alpha
      polypeptide in the epidermis prior to therapy, with a relative concentration of
      immunoprotein in the upper epidermal layers, compared with a more uniform
      distribution of immunoprotein after treatment, and in uninvolved skin of the same
      psoriatic patient. These studies extend our knowledge of the relationship between
      TGF-alpha and psoriatic skin.

PMID- 7519034
TI  - In vitro growth of human fetal CD34+ cells in the presence of various
      combinations of recombinant cytokines under serum-free culture conditions.
AB  - CD34+ cells were purified from midtrimester human fetal blood and adult bone
      marrow samples and seeded in serum-free fibrin-clot cultures in order to evaluate
      the number and the responsiveness to recombinant cytokines of pluripotent (CFU
      GEMM), erythroid (BFU-E), megakaryocyte (BFU-meg and CFU-meg) and
      granulocyte/macrophage (CFU-GM) haemopoietic progenitor cells. The number of the
      different haemopoietic progenitors/1 x 10(3) CD34+ cells, except CFU-meg, was
      significantly higher in fetal blood than in adult bone marrow in cultures
      stimulated by any combination of cytokines including interleukin-3 (IL-3),
      granulocyte/macrophage colony stimulating factor (GM-CSF) or stem cell factor
      (SCF) plus erythropoietin (Epo). Nevertheless, whereas adult BFU-E showed a
      maximal growth in the presence of Epo plus IL-3 or Epo plus SCF, fetal BFU-E
      showed an optimal growth in the presence of Epo alone, the sensitivity of fetal
      BFU-E to suboptimal concentrations of Epo being approximately 10-15-fold higher
      than that of adult BFU-E. Addition of optimal concentrations of IL-3, GM-CSF or
      SCF, alone or in various combinations, to Epo-containing cultures induced a
      significant increase in both the number and size of fetal CFU-GEMM, and CFU-GM,
      and a parallel decrease of fetal BFU-E. Finally, SCF potently synergized with IL
      3 in increasing the growth of both classes of fetal megakaryocyte progenitors,
      BFU-meg and CFU-meg.

PMID- 7519035
TI  - The in vitro effects of stem cell factor, interleukin 3 and granulocyte
      macrophage colony stimulating factor on haemopoietic progenitor cells from
      premature infants.
AB  - Circulating haemopoietic progenitor cells from premature infants were assessed
      for their ability to respond to interleukin 3, granulocyte-macrophage colony
      stimulating factor and stem cell factor (SCF) in vitro. All three cytokines
      increased the number of colonies derived from burst forming units erythroid (BFU
      E), colony forming units granulocyte-macrophage (CFU-GM) and multi-lineage
      progenitors (CFU-Mix) grown in the presence of erythropoietin (Epo). The size and
      haemoglobin content of BFU-E derived colonies also increased in the presence of
      the cytokines. Of those tested, SCF was found to be the most potent additive to
      Epo for the enhanced growth of BFU-E and CFU-Mix. In short-term liquid cultures
      without Epo, SCF alone induced globin synthesizing cells. Progenitors from
      premature infants were at least as responsive to all three cytokines as those
      from healthy adults. The use of SCF in combination with Epo in the prevention or
      treatment of anaemia in premature infants warrants further investigation.

PMID- 7519037
TI  - ADP causes partial degranulation of platelets in the absence of aggregation.
AB  - Whole blood flow cytometry has revealed that platelets undergo partial
      degranulation in response to ADP, in the absence of aggregation, as evidenced by
      the expression of the P-selectin and CD63 antigens of the alpha-granule and
      lysosomal membranes respectively. With maximum ADP (10(-5) M) fibrinogen bound to
      76.1 +/- 7.2% of platelets but P-selectin and CD63 antigen were expressed on 26.9
      +/- 9.8% and 8.6 +/- 3.5% of platelets respectively. Maximum fibrinogen binding,
      P-selectin and CD63 expression induced by alpha-thrombin were 96.1 +/- 1.4%, 92.8
      +/- 2.3% and 77.6 +/- 9.7% respectively. beta-thromboglobulin release from the
      ADP-stimulated platelets correlated closely with the expression of P-selectin and
      CD63 (r = 0.98 +/- 0.02 for both antigens). No platelet aggregates were seen by
      flow cytometry and the absence of aggregation was confirmed by single cell
      counting. Addition of the GPIIb-IIIa antagonist echistatin, at concentrations
      that totally blocked fibrinogen binding to ADP-stimulated platelets, had no
      effect on the expression of the granule membrane antigens. The partial
      degranulation of normal platelets was independent of thrombin generation since it
      was not inhibited by hirudin (5 units/ml). In conclusion, ADP is capable of
      causing partial degranulation of platelets independently of aggregation,
      fibrinogen binding or thrombin generation. Thus release of potent procoagulant,
      vasoactive and mitogenic substances from the platelets could continue in the
      presence of thrombin inhibitors and GPIIb-IIIa antagonists.

PMID- 7519038
TI  - Plasma granulocyte-colony stimulating factor concentrations ([G-CSF]) in the
      early neonatal period.
AB  - We studied G-CSF concentrations ([G-CSF]) at birth and their relationship with
      neutrophil count, incidence of infection, gestational age, labour, and the
      presence of maternal pregnancy-induced hypertension. Plasma [G-CSF] were
      significantly elevated in babies with suspected infection and in those of
      hypertensive mothers, compared to healthy babies delivered by elective caesarian
      section (median [range] = 3101 [75- > 5000] pg/ml and 153 [45-857] pg/ml versus
      32 [11-266] pg/ml; P < 0.0001); and were unrelated to neutrophil count and
      gestational age. Initial high concentrations (> 100 pg/ml) declined by 7 d (P <
      0.0001).

PMID- 7519036
TI  - Anaplastic large cell lymphoma (CD30 +/Ki-1+): results of a prospective clinico
      pathological study of 69 cases.
AB  - Sixty-nine anaplastic large cell lymphomas (ALCLs) were selected from an Italian
      comparative trial on MACOP-B and F-MACHOP. As no significant difference in
      effectiveness of the protocols emerged, they were considered homogeneously
      treated. The ALCLs were divided into two groups according to previously defined
      criteria: 41 were common type (ALCLs-CT) and 28 Hodgkin-related (ALCLs-HR). T
      cell phenotype was most common (58%), while B-cell, null and hybrid forms
      accounted for 27%, 13% and 2%. Clinically, ALCLs CT and HR differed as to mean
      age (27 v 34.3 years) and presentation; all ALCLs-HR showed mediastinal
      involvement, with bulky disease in 57%, and more frequent occurrence in stage II.
      In contrast, ALCLs-CT showed mediastinal masses in 58.5%, infrequently revealed
      bulky disease (24%), and were not specifically associated to stage. Among the
      ALCLs-CT, 68.4% achieved complete remission (CR), 24.4% partial remission (PR),
      one (2.4%) was resistant to therapy, and two (4.8%) had fatal drug toxicity. Of
      the ALCLs-HR, 67.8% reached CR, 14.3% PR, and 17.9% did not respond. In CR, ALCLs
      CT showed a greater tendency to relapse (32.1% v 14.2%). At present, 65.8% of
      ALCLs-CT and 67.8% of ALCLs-HR are alive with overall survival/disease-free
      survival averages of 31/27 and 29/24 months respectively. Our data emphasize
      that, independently of subtype, ALCLs benefit from the application of third
      generation protocols for high-grade non-Hodgkin's lymphomas.

PMID- 7519040
TI  - Successful reversal of neutropenia in Felty's syndrome with recombinant
      granulocyte colony stimulating factor.
AB  - We report two patients with Felty's syndrome and chronic skin ulcers treated
      successfully with recombinant granulocyte colony stimulating factor (GCSF). In
      both cases granulocytes returned to the normal range within days of starting
      treatment, and their cutaneous ulcers improved. In one patient granulocytes were
      maintained at normal levels with a regimen of GCSF 3 micrograms/kg twice weekly
      for 14 months.

PMID- 7519041
TI  - Marked and reproducible increase in trilineage blood cell counts by
      administration of granulocyte colony-stimulating factor in a patient with
      refractory anaemia with excess blasts in transformation.
AB  - We report a patient with refractory anaemia with excess blasts in transformation
      (RAEB-t) who presented with severe pancytopenia and received four intermittent
      series of granulocyte colony-stimulating factor (G-CSF) treatment over 1.5 years.
      In addition to the increase in mature neutrophils, platelet count and haemoglobin
      level were dramatically increased. These haematological improvements were
      dependent on G-CSF during these treatment series. Bone marrow colony assay
      revealed that G-CSF increased both CFU-E- and BFU-E-derived colonies in vitro.
      Clinical usage of G-CSF in myelodysplastic syndrome (MDS) is discussed, with
      particular emphasis on mechanisms of trilineage response.

PMID- 7519039
TI  - Sweet's syndrome during therapy with granulocyte colony-stimulating factor in a
      patient with aplastic anaemia.
AB  - A patient with aplastic anaemia developed Sweet's syndrome (a febrile
      neutrophilic dermatosis) during granulocyte colony-stimulating factor (G-CSF)
      therapy. Three repeated episodes of appearance and disappearance of erythematous
      nodules after administration and withdrawal of G-CSF confirmed that G-CSF induced
      Sweet's syndrome in the patient. Sweet's syndrome has been reported in patients
      with myelodysplastic syndrome and acute leukemia, but not in patients with
      aplastic anaemia. This is the first report of a patient with aplastic anaemia who
      developed G-CSF-induced Sweet's syndrome.

PMID- 7519042
TI  - Stable and temperature-sensitive transformation of rat kidney epithelial cells
      suppresses expression of acidic fibroblast growth factor 1 but activates
      secretion of fibroblast growth factor 3 (int-2) and vascular endothelial growth
      factor.
AB  - Rat kidney proximal tubule epithelial cells (RPTE) in primary culture express
      acidic fibroblast growth factor 1 (FGF-1). Transformation of RPTE by SV40 (SV
      RPTE) suppressed FGF-1 expression but activated secretion of FGF-like factor(s).
      SV-RPTE conditioned medium contained growth-promoting activity for SV-RPTE and
      human umbilical vein endothelial cells, indicating that both autocrine and
      angiogenic factors were secreted. Reverse transcriptase-polymerase chain reaction
      and Northern analysis for various FGFs showed that only FGF-3, also known as int
      2, mRNA was expressed in SV-RPTE. In addition, expression of mRNA for the heparin
      binding angiogenic factor vascular endothelial growth factor (VEGF) increased
      dramatically in SV-RPTE. Physical characterization of the activity in the SV-RPTE
      conditioned medium suggested that FGF-3 and VEGF contributed the autocrine and
      angiogenic activities, respectively. We also investigated FGF-3 and VEGF
      secretion in temperature-sensitive (ts) SV40-transformed RPTE. tsSV-RPTE had
      transformed properties resembling those of SV-RPTE only at the permissive
      temperature (33 degrees C), e.g., increased growth potential and anchorage
      independent growth. FGF-1 was expressed only at the nonpermissive temperature.
      VEGF mRNA levels and secretion of the human umbilical vein endothelial cell
      growth-promoting activity were reduced by switching tsSV-RPTE cells from 33
      degrees to 39 degrees C. However, FGF-3 mRNA levels were not affected
      significantly by the temperature switch suggesting that activation of VEGF and
      FGF-3 occurs through different mechanisms. These results indicate that FGF-1
      expression in RPTE is suppressed by SV40 transformation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7519043
TI  - Raf-1 is a necessary component of the mitogenic response of the human
      megakaryoblastic leukemia cell line MO7 to human stem cell factor, granulocyte
      macrophage colony-stimulating factor, interleukin 3, and interleukin 9.
AB  - We have examined the role of Raf-1 in the mitogenic response of the factor
      deprived human megakaryoblastic leukemia cell line MO7 to recombinant human
      granulocyte-macrophage colony-stimulating factor, interleukin 3, interleukin 9,
      and stem cell factor by using c-raf antisense oligodeoxyribonucleotides. Uptake
      of oligodeoxyribonucleotides by MO7 cells was maximal at 5-10 h in culture, and
      oligomers remained stable in these cells for at least 24 h. Treatment of MO7
      cells with the antisense oligomer resulted in intracellular oligomer/mRNA duplex
      formation followed by efficient translation blockade of c-raf-1. In contrast,
      sense and non-sense oligodeoxyribonucleotides failed to form intracellular
      duplexes and did not interfere with translation of c-raf-1, suggesting specific
      elimination of c-raf-1 by the antisense oligodeoxyribonucleotide. Furthermore,
      exposure of MO7 cells to c-raf-1 antisense prevented factor-induced nuclear
      translocation of Raf-1. Most importantly, proliferation of MO7 cells
      ([3H]thymidine incorporation) enabled by these growth factors was significantly
      reduced when the c-raf-1 antisense oligodeoxyribonucleotide was added to
      cultures, whereas the mitogenic response to these factors remained almost
      unaffected in the presence of sense and non-sense oligodeoxyribonucleotides.

PMID- 7519044
TI  - Chromosome abnormalities in benign prostatic hyperplasia.
AB  - We combined conventional cytogenetic analysis and fluorescence in situ
      hybridization of short-term cultures of 28 samples from benign prostatic
      hyperplasia. Loss of the Y chromosome was the most common chromosome change,
      followed by trisomy 7. Trisomy 7, however, may be unrelated to the origin of
      benign prostate hyperplasia, in which the only and not very specific change seems
      to be the loss of the Y chromosome.

PMID- 7519046
TI  - A t(10;17) translocation creates the RET/PTC2 chimeric transforming sequence in
      papillary thyroid carcinoma.
AB  - Activation of the RET protooncogene tyrosine kinase (tk) by fusion with other
      genes is a frequent finding in papillary thyroid carcinoma. The tk domain of
      proto-RET can be fused either with the D10S170 gene generating the RET/PTC1
      transforming sequence or with sequences belonging to the gene encoding the
      regulatory subunit RIA of c-AMP-dependent protein kinase A, thus forming the
      RET/PTC2 oncogene. We have previously shown that an inversion of chromosome 10,
      inv(10)(q11.2q21), is responsible for the generation of the RET/PTC1. Here we
      report that a chromosomal translocation, t(10;17)(q11.2;q23), juxta-poses the tk
      domain of the RET protooncogene, which resides on chromosome 10, to a 5' portion
      of the RIA gene on chromosome 17, leading to the formation of the chimeric
      transforming gene RET/PTC2. The finding of the transforming protein in primary
      tumor cell extracts supports the conclusion that RET/PTC2 activation plays a role
      in papillary thyroid tumorigenesis.

PMID- 7519047
TI  - Chromosome 13 transfer provides evidence for regulation of RB1 protein
      expression.
AB  - The human retinoblastoma susceptibility gene (RB1) located on chromosome 13 has
      been shown to function as a growth/tumor suppressor gene in a large number of
      human cancers. Although constitutive expression has been observed in most
      cultured cells and normal tissues, overexpression of RB1 protein has not been
      well documented. Perhaps regulating the level of normal RB1 protein expression is
      one of several ways of controlling its function. To test this hypothesis, we
      transferred normal copies of chromosome 13 via microcell fusion into the human
      fibrosarcoma cell line HT1080. Microcell hybrids were generated that contained
      one, two, or three extra copies of the transferred fibroblast chromosome 13.
      Compared to the parental cell line, the hybrids were completely unaltered with
      respect to several properties in vitro and in vivo, including morphology, growth
      rate, and tumor formation. Northern blot analysis revealed a stepwise increase in
      RB1 mRNA expression which increased in proportion to the number of alleles
      present in each cell line. Although RB1 protein exhibited correct nuclear
      localization and was phosphorylated in a normal cell cycle-dependent manner in
      the hybrids, the increased level of protein expression in each hybrid was nearly
      identical and did not increase beyond a threshold amount, although mRNA
      expression continued to increase. These results demonstrate that HT 1080 cells
      can tolerate an increase level of RB1 protein, but that expression beyond a
      certain level may be down-regulated. These transfer studies provide evidence for
      regulation of RB1 protein expression and may suggest an alternative form of
      monitoring and controlling normal RB1 functioning.

PMID- 7519045
TI  - Molecular analysis of simple variant translocations in acute promyelocytic
      leukemia.
AB  - The primary cytogenetic abnormality in acute promyelocytic leukemia (APL; FAB M3)
      is a reciprocal translocation, t(15;17)(q22;q12), which serves to fuse the PML
      gene on chromosome 15 to the retinoic acid receptor alpha (RARA) gene on
      chromosome 17. A PML-RARA fusion message transcribed from the der(15) is thought
      to mediate leukemogenesis. Two APL patients with simple variants of this
      translocation, t(3;15)(q21;q22) and t(X;15)(p11;q22), have previously been
      reported who lack cytogenetic involvement of chromosome 17, although their
      breakpoint positions on chromosome 15 still suggest the involvement of the PML
      gene. Here we report on a combined analysis by molecular genetics and in situ
      hybridization of these two patients, in which we wanted to determine whether the
      PML gene has alternative fusion partners or whether cryptic rearrangement of the
      RARA locus has occurred instead. A cryptic involvement of RARA was demonstrated
      in both patients by a combination of Southern analysis, reverse transcription
      coupled to PCR (RT-PCR), and fluorescence in situ hybridization. The results
      indicate an absolute requirement for the rearrangement of the RARA gene in the
      pathogenesis of APL and underline the importance of RARA during normal myeloid
      differentiation.

PMID- 7519049
TI  - Evidence that wild-type TP53, and not genes on either chromosome 1 or 11,
      controls the tumorigenic phenotype of the human fibrosarcoma HT1080.
AB  - The specific transfer of normal chromosomes via microcell fusion has been
      instrumental in identifying putative tumor suppressor gene loci in a variety of
      human cancers. Using this same technique it has been proposed that the
      tumorigenicity of the human fibrosarcoma cell line HT1080 is controlled by
      functionally distinct tumor suppressor genes on human chromosomes I and II. To
      address these results and perhaps further localize the suppressive effect to
      particular regions on these two chromosomes, we transferred into HT1080 seven
      different fibroblast-derived human chromosomes containing either intact or
      discrete portions of chromosome I or II. Interestingly, we found no evidence of
      genes on these chromosomes that could alter the growth of HT1080 either in vitro
      or in vivo. Based on these results we were left with the possibility that a gene,
      or genes, residing on an entirely different chromosome(s) was involved in the
      tumorigenesis of HT1080. Since TP53 mutation has been documented in a variety of
      human tumor types, and we found both copies of TP53 to be mutated in HT1080, we
      were prompted to examine its role by both cDNA transfection and chromosome
      transfer. Although by cDNA transfection we found that expression of exogenous
      wild-type TP53 was incompatible with continued proliferation of HT1080 cells in
      vitro, chromosome 17 transfer studies revealed that a more physiologic expression
      of exogenous wild-type TP53 could be tolerated in vitro while being completely
      incompatible with growth in vivo. These studies demonstrate a differential effect
      of TP53 growth inhibition and clearly show that TP53 tumor suppressing function
      can be independent from its potent growth suppressing effect in vitro.

PMID- 7519048
TI  - MDM2 gene amplification correlates with ring chromosome in soft tissue tumors.
AB  - The human homolog of the murine double minute type 2 gene (MDM2) has been cloned
      and mapped to 12q13-14. The gene presumably functions as a cellular regulator and
      mediator of TP53 function. Amplification of the MDM2 gene has recently been
      observed in soft tissue sarcoma and in osteosarcoma. We studied MDM2
      amplification in a series of 94 mesenchymal tumors and found 3-20-fold
      amplification in 20 tumors: in 10 of 49 malignant fibrous histiocytomas (MFH), in
      1 of 2 pleomorphic liposarcomas, in 6 of 7 atypical lipomas, and in 3 of 12
      typical lipomas. Normal hybridization patterns were detected in all 16 myxoid
      liposarcomas, in all 3 leiomyosarcomas, and in all 5 leiomyomas studied. The MDM2
      amplification correlated with the presence of marker ring chromosomes; of the 10
      MFH with MDM2 amplification, 5 had ring chromosomes, compared to 4 of 39 without
      MDM2 amplification, and all 9 liposomas with MDM2 amplification had ring
      chromosomes, in 5 of the tumors as the sole karyotypic anomaly. The correlation
      between ring chromosomes and MDM2 gene amplification indicates that the marker
      rings of MFH and of atypical lipoma often harbor genetic material derived from
      chromosome 12.

PMID- 7519050
TI  - Breakpoints of Burkitt's lymphoma t(8;22) translocations map within a distance of
      300 kb downstream of MYC.
AB  - The variant translocation t(8;22) in Burkitt's lymphoma (BL) cells joins band q24
      of chromosome 8 distal to the proto-oncogene MYC to the immunoglobulin lambda
      locus. The distribution of breakpoints on chromosome 8 of 11 cell lines with
      t(8;22) has been investigated by in situ fluorescence hybridization and pulsed
      field gel electrophoresis. We show that these chromosomal breakpoints generally
      fall within a region of about 300 kb 3' of MYC and that at least 8 out of 11
      affect the previously characterized transcriptional unit PVT1. Comparable results
      were obtained in earlier experiments analyzing the variant t(2;8). Recently, in a
      series of BL cells carrying t(8;14), breakpoints upstream of MYC have been
      described at a similar distance. Therefore, our results suggest that deregulation
      of MYC by the immunoglobulin loci can occur at a distance of up to about 350 kbp
      of MYC.

PMID- 7519051
TI  - A synovial sarcoma with a complex t(X;18;5;4) and a break in the ornithine
      aminotransferase (OAT)L1 cluster on Xp11.2.
AB  - The initial cytogenetic analysis of a biphasic synovial sarcoma revealed complex
      anomalies involving six different chromosomes:
      46,Y,t(X;18;5;4)(p11;q11;p13;q12),t(2;5)(q35;q11). After fluorescence in situ
      hybridization (FISH) analysis, using chromosome X-specific plasmid library and
      YAC probes, the situation appeared to be even more complex, with an insertion of
      part of the X chromosome short arm into the der(5)t(5;18). In spite of these
      complex chromosomal rearrangements, the Xp11 breakpoint could be mapped to within
      the ornithine aminotransferase (OAT)L1 cluster, very similar to that reported
      previously for the standard t(X;18)(p11;q11) in synovial sarcomas. These findings
      suggest common pathogenetic pathways in these cytogenetically different but
      morphologically similar tumors.

PMID- 7519052
TI  - Comparative genomic hybridization as a tool to define two distinct chromosome 12
      derived amplification units in well-differentiated liposarcomas.
AB  - Well-differentiated liposarcomas (WDLPS) are frequently characterized by a near
      diploid karyotype with supernumerary ring and/or giant rod-shaped marker
      chromosomes. We have shown, using fluorescence in situ hybridization (FISH) and
      molecular strategies, that these markers contain chromosome 12-derived sequences.
      Here we report the analysis of six WDLPS for the presence of amplified DNA
      segments by means of the recently developed comparative genomic hybridization
      (CGH) strategy. Two distinct chromosome 12-derived amplification units could be
      identified in all tumors examined, one located in the q14-q15 region as expected,
      the second unexpectedly mapping to q21.3-q22. Our results indicate that the
      concerted amplification of these two distinct regions on the long arm of
      chromosome 12 may be a consistent characteristic of WDLPS. These amplifications
      are most likely directly related to the presence of supernumerary ring and/or
      giant marker chromosomes in this group of soft tissue tumors.

PMID- 7519053
TI  - Allelic loss at 1p is associated with tumor progression of meningiomas.
AB  - Next to chromosome 22 anomalies, deletions of the short arm of chromosome 1 have
      previously been described as the most frequent alteration detected by cytogenetic
      analysis of meningiomas. To determine the incidence of these deletions, we have
      analyzed a series of 50 meningiomas for the loss of alleles at four chromosome 1
      loci. Thirteen samples displayed LOH for the markers studied; in one instance,
      the results were compatible with loss of the entire chromosome 1, whereas in the
      other 12 samples deletions of the short arm were observed. Eleven of the
      meningiomas had previously been shown to have loss of alleles on chromosome 22,
      and 12 of them were characterized by increased tumor aggressiveness. These
      findings suggest that deletion of Ip (or the alteration of a locus located there)
      might represent a secondary, but nonrandom alteration in meningiomas, perhaps
      contributing to meningioma tumor progression.

PMID- 7519054
TI  - Sphingosine inhibits the synthesis of RNA primers by primase in vitro.
AB  - We have previously shown the presence of sphingomyelin and sphingomyelinase in
      cell nuclei, suggesting that they may play a role in the intranuclear production
      of sphingosine, a potent bioactive molecule modulating diverse cellular
      functions. In the present study, the direct effects of sphingosine (C18:1) on the
      activity of DNA replication/repair polymerases were studied in vitro. Sphingosine
      had no effect on DNA polymerases alpha and beta and slightly inhibited DNA
      polymerases gamma, delta, and epsilon. In contrast, sphingosine strongly
      inhibited the activity of primase in a dose-dependent manner. On the other hand,
      dihydrosphingosine (C18:0), glycolipids, sphingomyelin, and ceramide had no
      effect on primase activity. Sphingosine equally inhibited the activity of primase
      complexed with DNA polymerase alpha, as well as its free form, with a Ki value of
      4 microM. A gel-retardation analysis showed that the binding of primase with 32P
      labeled template DNA was suppressed by sphingosine. Inhibition by sphingosine was
      competitive with the DNA template, but not with the substrate NTPs. After product
      analysis, a dose-dependent decrease in the amount of RNA primer products,
      consisting mainly of 10- and 11-mers, was observed in the presence of
      sphingosine, indicating that it inhibits the synthesis of RNA primers by primase.
      Sphingosine, however, had no effect on T7 RNA polymerase.

PMID- 7519055
TI  - Epitope analysis of T- and B-cell response against the human beta 1-adrenoceptor.
AB  - Several reports have recently raised the possible significance of the presence of
      autoantibodies against the beta 1-adrenoceptor in patients with idiopathic
      dilated cardiomyopathy. An investigation was thus initiated to study the immune
      response against this receptor at the T-cell and the B-cell level. Using
      membranes of E coli transfected with the human beta 1-adrenoceptor gene as
      immunogen, T-helper cells of the immunized mice were stimulated with synthetic
      peptides derived from the receptor and predicted to be immunogenic to assess the
      T-cell immunodominant regions of the receptor. Three peptides derived from the
      second transmembrane region, from the second extracellular loop and from the C
      terminal domain were shown to be stimulatory. Synthetic peptides, derived from
      two domains of the receptor which could be potential targets for autoantibodies,
      yielded an antibody response after immunization with the free peptides. The
      peptide derived from the N-terminal region yielded antibodies which recognized
      the receptor in immunoblot and by immunoprecipitation but they had no functional
      effect on the receptor. The peptide derived from the second extracellular loop
      yielded antibodies which recognized the receptor in immunoblot and by
      immunoprecipitation of the free receptor and which had a pharmacological effect
      on the receptor. The second extracellular loop thus contains T- and B-cell
      epitopes which could be involved in the autoimmune process.

PMID- 7519056
TI  - Production of anti-peptide antibodies directed against the first and the second
      extracellular loop of the human serotonin 5-HT1A receptor.
AB  - The second extracellular loop of the beta-adrenergic and muscarinic acetylcholine
      receptors was shown to be an autoimmune target for antibodies in several
      autoimmune diseases. These autoantibodies and the antibodies induced against
      synthetic peptides corresponding to this loop have pharmacological and
      physiological properties upon receptor recognition which could explain their
      pathophysiological role. We here describe the immune properties of the first and
      second extracellular loops of another G protein-coupled receptor, the serotonin 5
      HT1A receptor. The injection in rabbits of the free peptides Y16L and G21G
      corresponding to the first and second extracellular loops respectively induced
      anti-peptide antibodies with high titer, demonstrating the presence of a T-cell
      epitope on each peptide. Interestingly, in contrast to the G21G peptide that
      induced only anti-G21G antibodies (Ab-2 antibodies), the Y16L peptide induced two
      populations of antibodies. One recognized only the Y16L peptide (Ab-1
      antibodies), the other recognized both peptides (Ab-12 antibodies). This reflects
      the presence on the two peptides of at least two B-cell epitopes. The fact that
      the G21G peptide induces only one antibody population might indicate that it
      possesses one immunodominant epitope involved in the Ab-2 antibody production and
      one cryptic epitope involved in the cross-reaction with the anti-Y16L antibodies.
      But only Ab-2 antibodies were able to recognize specifically the human protein
      receptor expressed in E coli in immunoblot.

PMID- 7519057
TI  - Interaction of Hoechst 33258 with a DNA triple helix.
AB  - The interaction of Hoechst 33258 molecule, a minor groove binding drug, with T-A
      T triple helix and A-T double helix was studied using circular dichroism
      spectroscopy and thermal denaturation. The triple helix consisted of an
      oligonucleotide (dA)12-x-(dT)12-x-(dT)12, where x is a hexa-ethylene glycol chain
      bridged between the 3' phosphate of one strand and the 5' phosphate of the
      following strand. This oligonucleotide is able to fold back on itself to form a
      very stable triplex. Circular dichroism spectroscopy demonstrates that Hoechst
      33258 can bind to the triple helical structure. Spectral analysis shows that the
      bound drug exhibits a conformation and an environment slightly different in
      double-stranded and in triple-stranded structure. The affinity to the triple
      stranded structure is found smaller than to the double stranded one. Thermal
      denaturation experiments demonstrate that Hoechst 33258 destabilizes the triplex
      whereas it stabilizes the duplex.

PMID- 7519059
TI  - [Exogenous iron and gamma-radiation induces synthesis of NO-synthetase in mouse
      liver].
AB  - The inhibitor of protein biosynthesis, cycloheximide (CHI) and the exogenous
      antioxidant, phenazan, attenuated the synthesis of nitric acid oxide (NO) in
      mouse liver in vivo induced by gamma-irradiation, bacterial lipopolysaccharide
      (LPS) or LPS+Fe(2+)-citrate treatment of experimental animals. The rate of NO
      synthesis was followed by accumulation of paramagnetic mononitrosyl iron
      complexes with the exogenous ligand--diethyldithiocarbamate (MNIC-DETC). The
      latter were formed as a result of NO binding to selective NO traps (DETC
      complexes with exogenous or endogenous Fe2+ ions) and measured by the EPR method.
      A conclusion is drawn that the activation of NO biosynthesis under the action of
      gamma-irradiation, LPS or LPS+Fe(2+)-citrate treatment was due to the induction
      of NO synthase synthesis inhibited by CHI. This process is initiated by active
      oxygen species, presumably due to the activation of the transcription factor,
      NFkB protein. The accumulation of active oxygen species was inhibited by the
      antioxidant, phenazan.

PMID- 7519058
TI  - [Detection of antigenic determinants of alcohol dehydrogenase for certain
      biological species using antipeptide antibodies].
AB  - The structural and functional peculiarites of alcohol dehydrogenases (ADH) of
      some biological species have been studied using antipeptide antibodies (AB). The
      synthetic peptides were used which corresponded to the functionally important
      sites (1-14, 93-115, 265-276) of equine liver ADH. Conjugates of peptides with
      protein carriers were obtained and used for immunization of laboratory animals.
      It was shown that the antipeptide antibodies formed therefrom could interact with
      the corresponding synthetic peptides, with conjugates derived from them as well
      as with the native enzyme. The results of cross-reactivity of antipeptide AB with
      ADH from other biological sources suggest that amino acid sequences (1-14), (93
      115) and (265-276) contain common antigenic determinants for the corresponding
      ADH from animal sources. According to computer prediction data for linear
      epitopes of equine liver ADH, sequence (93-115) comprises amino acid residues of
      the antigenic determinants with enhanced conformational rigidity which is
      consistent with the literary data on the functional significance of this site
      (the loop ligating the second Zn atom). Sequences (1-14) and (265-276) contain
      amino acid residues capable of interacting with AB and pertaining, in all
      probability, to antigenic determinants formed by mobile structures.

PMID- 7519060
TI  - [Studies of the resistance of the human immunodeficiency virus to azidothymidine.
      I. Kinetic studies of the interaction between reverse transcriptase and a series
      of its mutant forms with substrates and azidothymidine-5'-trisphosphate].
AB  - Prolonged therapy of AIDS patients with azidothymidine results in the development
      of resistance to the drug. This phenomenon is accompanied by the appearance of
      point mutations in the pol gene coding for reverse transcriptase (RT). Kinetic
      studies of interactions of wild type RT and its forms containing the above
      mentioned mutations with substrates and azidothymidine 5'-triphosphate have been
      carried out. Considerable differences in the affinities of RT and the mutants for
      RNA and DNA heteropolymer templates were established. The mutations did not
      affect the RT affinity for dNTP; however, its location influenced considerably
      the inhibition of the reaction with azidothymidine 5'-triphosphate.

PMID- 7519061
TI  - Depressive mania versus agitated depression: biogenic amine and hypothalamic
      pituitary-adrenocortical function.
AB  - The existence of mixed affective states challenges the idea of specific
      biological abnormalities in depression and mania. We compared biogenic amines and
      hypothalamic-pituitary-adrenocortical (HPA) function in mixed manic (n = 8), pure
      manic (n = 11), agitated bipolar depressed (n = 20), and nonagitated bipolar
      depressed (n = 27) inpatients (Research Diagnostic Criteria). Mixed manics met
      Research Diagnostic Criteria for primary manic episodes and also met criteria for
      major depressive episodes except for duration. The norepinephrine metabolite
      methoxyhydroxy phenthylene glycol (MHPG) was higher in cerebrospinal fluid from
      mixed manic than from agitated depressed patients, consistent with differences
      previously reported between the overall samples of depressed and manic patients.
      Similarly, patients in a mixed state had higher urinary excretion of
      norepinephrine (NE) and elevated output of NE relative to its metabolites. HPA
      activity was similar in mixed manic and agitated depressed patients. These data
      suggest that mixed manics combine certain biological abnormalities considered to
      be characteristic of mania and of depression.

PMID- 7519063
TI  - [The limits of surgical therapy and intensive care].

PMID- 7519062
TI  - [Comparison of 5% human albumin and 6% 200/0.5 HES as exclusive colloid
      components in large surgical interventions].
AB  - OBJECTIVE: It was the purpose of the following study to compare effects of 6%
      hydroxyethyl starch 200/0.5 (HES) and albumin 5% (HA5) on haemostasis,
      haemodynamics, oncotic function and plasmatic homoeostasis. METHODS: In 2
      randomised groups of 20 patients each undergoing large surgery (criteria of
      exclusion: anaemia, renal, liver, and coagulation disorders, ASA classification >
      III) we treated up to 1000 ml with colloid solution, from 1000 ml up to 5000 ml
      with packed red blood cells (PRBC) and colloid solution (1:1) and above 5000 ml
      with PRBC and fresh frozen plasma (1:1). Group HES received HES and group HA5
      albumin as exclusive colloid component and both continuously lactated Ringers' at
      a rate of 500 ml/h. We measured the parameters before operation, after each 1000
      ml colloid up to 3000 ml application and at the end of operation and we
      registered total blood output/intake. RESULTS: We found comparable amounts of
      blood loss and blood intake (mean total amount of colloid solution: HES 2044 +/-
      579 ml; HA5 2547 +/- 980 ml). We didn't find any differences in haemodynamics nor
      in haematocrit, platelets or global coagulation parameters which only showed
      dilutional influences. Differences existed in total serum protein (HES 32.8 +/-
      6.5 gr/l; HA5 54 +/- 5.5 gr/l at OP's end); however COP was maintained in both
      groups during the whole study period at normal ranges. Plasmatic haemostasis
      showed to a large extent corresponding values. Remarkable was the development of
      a metabolic acidosis in the HA5 group. CONCLUSION: Regarding total blood
      output/intake, haemodynamic functions, haematological parameters, coagulation,
      oncotic function, and plasmatic homoeostasis, HES is a safe colloid if contra
      indications are taken into account, capable of replacing albumin 5% entirely as a
      colloid component of treatment of even large blood losses intraoperatively above
      the recommended dose of 20 ml/kg BW/d.

PMID- 7519064
TI  - [Analysis of serum antibodies to nerve tissue antigens in patients with lateral
      amyotrophic sclerosis].
AB  - We used non-direct immunofluorescence microscopy, immunoblotting and affinity
      chromatography on A-protein Superose to study antibodies to neural tissue
      antigens in sera from 11 patients with ALS and from 10 healthy donors. In all
      sera the majoric antigens had molecular masses of 150-200kD, 70kD and 50kD. No
      consistent differences were found between ALS patients and controls. Antibodies
      to 50kD and 70kD proteins from patients with ALS were found to be mostly IgM,
      whereas antibodies from control sera were mostly IgG. Antibodies to high
      molecular weight proteins (150-200kD) in ALS and controls belonged to both
      classes of immunoglobulins. Immunoblotting studies of neural tissue proteins
      after treatment blots with alkaline phosphatase showed considerable decrease of
      antibodies binding to neural tissue antigens in sera of ALS patients. The same
      results were obtained by immunofluorescence assay. The alkaline phosphatase
      experiments suggest that in ALS patients the sera antibodies are directed mainly
      against phosphoepitopes in protein antigenic determinants of the neural tissue.
      This results can lead to conclusion of a role for the altered phosphorylation of
      the neural proteins in the ALS pathogenesis.

PMID- 7519065
TI  - [Effect of substance P on survival of rats after cerebral ischemia: the effect
      depends on behavior type].
AB  - In rats with different behaviour types in tests of "open field" and "forced
      swimming", influence of intraperitoneal administration of P-substance (PC)
      neuropeptide to survival and structural-metabolic changes in brain after double
      sided ligating of carotid arteries. It was established that PC exerts different
      influence on stability to circulating cerebral hypoxia according to behaviour
      types: it increases stability in rats with passive behaviour type, decrease
      stability in rats with active behaviour type and does not influence on rats with
      middle behaviour type. Results shows the necessity of individual approach to
      peptide use with the view to increase stabilization to cerebral ischemia.

PMID- 7519067
TI  - [Effect of the Ly2 molecule on the function of alloantigen-specific effector
      cytotoxic T-lymphocytes as a function of the variability of their receptors'
      affinity].
AB  - To study T cell receptors' affinity alloantigen-specific anti-K cytotoxic T
      lymphocytes (CTL) were divided on fractions by elution from donor K and third
      party macrophage monolayers. The functional activity of CTL was suppressed by
      anti--Ly2 monoclonal antibodies (mAb), 51-Cr-labelled transformed fibroblasts (L
      cells) transferred with the H-2K gene were used as targets. The results
      demonstrate that primary CTL enriched on third-party macrophage monolayers are
      the most sensitive to anti-Ly2 mAb. T-cells exhausted on third-party monolayer
      and then enriched on donor monolayer were resistant to treatment with the mAb.
      Secondary CTL enriched on donor monolayer were resistant to treatment with anti
      Ly2 mAb even should they were not exhausted on third-party monolayer. These
      results show that Ly2 (CD8) molecule plays an essential role in the interaction
      of CTL with MHC class I molecule only if T-cell receptor has low affinity.

PMID- 7519066
TI  - [Effect of endogenous metabolites on autoregulation and dilational reserve of
      coronary vessels].
AB  - The experiments have been performed on isolated Langendorff rat's hearts.
      Perfusion pressure (PP) has been increased from 40 to 120 mm Hg by steps. It has
      been found out, that captopril, indomethacin and verapamil (blockers of the
      angiotensin-converting enzyme, eicosanoids synthesis and calcium channels,
      respectively) increased volume velocity of coronary flow (VVCF) at PP within the
      range of 80-120 mm Hg, decreased the value of the autoregulation index and the
      coronary vasodilatory reserve by 28-39%, apparently due to decrease of the basal
      tone of coronary vessels, while the maximum reactive hyperemia coronary flow was
      not changed thereby. The blockade of No-synthase by NG-monomethyl-l-arginine (NG
      MMLA) caused reduction of VVCF at PP 40 mm Hg by 28.5%, the autoregulation index
      by 79% and the coronary reserve by 29% due to reduction of reactive hyperemic
      flow. Captopril and NG-MMLA did not change while verapamil and indomethacin
      decreased intraventricular pressure. Thus, the decrease of the VVCF, caused by NG
      MMLA and its increase caused by addition of inhibitors could be connected with
      inhibition of the synthesis of substances modulating autoregulation of coronary
      blood flow, and obviously did not depend on changes in functional activity of
      myocardium.

PMID- 7519068
TI  - [Quantitative analysis of keratin SH-groups in human epidermis (a new
      micromethod)].
AB  - Micromethod of quantitative differentiation of keratin SH-groups has been
      established. It lets define SH-groups of cysteine in polypeptide chain in range
      of 0.05-0.07 mg/ml.

PMID- 7519069
TI  - Staphylokinase, a fibrin-specific plasminogen activator with therapeutic
      potential?

PMID- 7519070
TI  - Characterization of murine CD34, a marker for hematopoietic progenitor and stem
      cells.
AB  - CD34 is expressed on human hematopoietic stem and progenitor cells, and its
      clinical usefulness for the purification of stem cells has been well established.
      However, a similar pattern of expression for murine CD34 (mCD34) has not yet been
      determined. Two polyclonal anti-mCD34 antibodies that specifically recognize both
      endogenous and recombinant murine CD34 were developed to characterize the mCD34
      protein and to determine its pattern of expression on murine cell lines and
      hematopoietic progenitor cells. Fluorescence-activated cell sorter analysis
      showed that mCD34 is expressed on NIH/3T3 embryonic fibroblasts, PA6 stromal
      cells, embryonic stem cells, M1 leukemia cells, and a subpopulation of normal
      bone marrow cells. Murine CD34 was found to be a glycoprotein expressed on the
      cell surface as either a full-length (approximately 100 kD) or truncated
      (approximately 90 kD) protein in NIH/3T3 and PA6 cells. Recombinant full-length
      CD34, when expressed in the CHO-K1 cell line, had a molecular weight of
      approximately 105 kD. Full-length CD34 expressed on M1 leukemia cells, had a
      higher apparent molecular weight (110 kD). These results suggest that there are
      glycosylation differences between CD34 expressed by different cell types. The
      full-length form, but not the truncated form, is a phosphoprotein that is
      hyperphosphorylated in response to 12-0-Tetradecanoyl phorbol 13-acetate
      treatment, suggesting potential functional differences between the two forms.
      Selection of the 3% highest-expressing CD34+ bone marrow cells enriched for the
      hematopoietic precursors that form colony-forming unit-spleen (CFU-S), CFU
      granulocyte-macrophage, and burst-forming unit-erythroid. Transplantation of
      lethally irradiated mice with these cells demonstrated both short- and long-term
      repopulating ability, indicating that this population contains both functional
      hematopoietic progenitors and the putative stem cell. These antibodies should be
      useful to select for murine hematopoietic stem cells.

PMID- 7519071
TI  - Eradication of minimal disease in severe combined immunodeficient mice with
      disseminated Daudi lymphoma using chemotherapy and an immunotoxin cocktail.
AB  - Severe combined immunodeficient (SCID) mice injected intravenously with a human
      Burkitt's lymphoma cell line (Daudi) develop disseminated lymphoma (SCID/Daudi),
      which is fatal in 100% of the mice. Early treatment of these mice with either an
      immunotoxin (IT) cocktail (consisting of anti-CD19-ricin A chain plus anti-CD22
      ricin A chain) or chemotherapy significantly prolonged survival but was not
      curative. Combination therapy with the IT cocktail and any one of three
      chemotherapeutic drugs (doxorubicin, cytoxan, or camptothecin) cured the mice.
      Cure was demonstrated by both histopathologic examination of treated mice and,
      more importantly, by adoptive transfer of cells from organs of the cured mice to
      naive SCID mice where 100 tumor cells would have caused disease in the
      recipients. These results provide a strong rationale for combining IT therapy
      with conventional chemotherapy in the treatment of B-cell neoplasia.

PMID- 7519072
TI  - Characterization and purification of osteogenic cells from murine bone marrow by
      two-color cell sorting using anti-Sca-1 monoclonal antibody and wheat germ
      agglutinin.
AB  - Osteogenic cells were sorted from bone marrow of 5-fluorouracil (5-FU)-treated
      mice based on light scatter characteristics, Sca-1 expression, and their binding
      to wheat germ agglutinin (WGA). Four sort gates were established using forward
      (FSC) and perpendicular (SSC) light scatter and were denominated as FSChigh
      SSClow, FSClow SSChigh, FSClow SSClow, and FSChigh SSChigh cell. Cells from the
      FSChigh SSChigh gate, but not from the other gates, synthesized alkaline
      phosphatase, collagen, and osteocalcin and formed a mineralized matrix in
      culture. The number of osteoprogenitor cells was significantly enriched after
      depleting the 5-FU bone marrow from cells of the lymphoid and myeloid lineage,
      eg, T cells, B cells, natural killer cells, granulocytes, macrophages, and
      erythrocytes. Approximately 95% of the FSChigh SSChigh cell population of this
      "lineage-negative" (Lin-) marrow expressed the Sca-1 antigen (Sca-1+) and bound
      WGA. Three additional sort windows were established based on WGA binding
      intensity and were denominated as Sca-1+ WGAdull, Sca-1+ WGAmedium, and Sca-1+
      WGAbright. Cells from the Sca-1+ WGAbright gate, but not from the other gates,
      synthesized bone proteins and formed a mineralized matrix. However, they lost
      this capacity upon subcultivation. Further immunophenotypic characterization
      showed that FSChigh SSChigh Lin- Sca-1+ WGAbright cells expressed stromal (KM16)
      and endothelial (Sab-1 and Sab-2) markers, but not hematopoietic surface markers
      such as c-kit and Thy1.2. Sorted FSChigh SSChigh Lin- Sca-1+ WGAbright cells form
      three-dimensional nodules that stain with the von Kossa technique and contain
      osteoblast and osteocyte-like cells.

PMID- 7519073
TI  - Distribution of receptors for granulocyte-macrophage colony-stimulating factor on
      immature CD34+ bone marrow cells, differentiating monomyeloid progenitors, and
      mature blood cell subsets.
AB  - Biotin-labeled granulocyte-macrophage colony-stimulating factor (GM-CSF), in
      combination with phycoerythrin-conjugated streptavidin, enabled flow cytometric
      analysis of specific cell-surface GM-CSF receptors on rhesus monkey bone marrow
      (BM) and peripheral blood (PB) cells. GM-CSF receptors were readily detected on
      PB monocytes and neutrophils, but not on lymphocytes. In BM, GM-CSF receptors
      were identified on monocyte and neutrophil precursors and on subsets of cells
      that expressed the CD34 antigen. CD34+ cells with high GM-CSF-receptor expression
      coexpressed high levels of the class II major histocompatibility antigen RhLA-DR,
      whereas CD34+/RhLA-DRlow cells, which represent developmentally earlier cells,
      were either GM-CSF-receptor negative or expressed GM-CSF receptors at very low
      levels. The fluorescence histogram of CD34bright/RhLA-DRdull cells stained with
      biotin-GM-CSF showed that at least a fraction of these cells expressed low levels
      of GM-CSF receptors. CD34+ cells with high GM-CSF-receptor expression, purified
      by cell sorting, did not form colonies in culture or proliferate in response to
      GM-CSF. Instead, GM-CSF stimulation resulted in terminal differentiation into
      adherent cells, showing that these cells represented monocyte precursors. A
      distinct subset of CD34+ cells expressed GM-CSF receptors at low-to-intermediate
      levels and proliferated strongly in the presence of GM-CSF during short-term
      culture, but produced very few erythroid or monomyeloid colonies after longer
      culture periods. Most colony-forming cells, also those responsive to GM-CSF
      alone, were recovered in the subset of CD34+ cells on which GM-CSF receptors were
      virtually undetectable. These cells showed weaker proliferation in short-term
      proliferation assays than the CD34+/GM-CSF-receptor-intermediate cells,
      consistent with an immature phenotype. The results show that GM-CSF-receptor
      expression is initiated in a subset of immature, CD34bright/RhLA-DRdull cells and
      is progressively increased during differentiation into mature granulocytes and
      monocytes. The method used provides a new way to deplete developmentally early
      CD34+ cell of differentiating granulocyte and monocyte precursor cells.

PMID- 7519074
TI  - Direct synergistic effects of interleukin-7 on in vitro myelopoiesis of human
      CD34+ bone marrow progenitors.
AB  - Interleukin-7 (IL-7) is an important growth factor in B and T lymphopoiesis in
      mouse and human, whereas IL-7 has been regarded to lack proliferative effects on
      cells within the myeloid lineage. However, we have recently reported that IL-7
      potently can enhance colony stimulating factor (CSF)-induced myelopoiesis from
      primitive murine hematopoietic progenitors, showing a novel role of IL-7 in early
      murine myelopoiesis. Using CD34+ human hematopoietic progenitor cells, we show
      here a similar role of IL-7 in human myelopoiesis, although interesting
      differences between the two species were found as well. Although purified
      recombinant human (rh)IL-7 alone did not induce any proliferation of CD34+ cells,
      IL-7 in a concentration-dependent manner enhanced the colony formation induced by
      all four CSFs up to threefold. Furthermore, stem cell factor (SCF)-induced
      granulocyte-macrophage (GM) colony formation was increased fourfold in the
      presence of IL-7. Single-cell cloning assays showed that these synergistic
      effects of IL-7 were directly mediated on the targeted progenitors, and that IL-7
      increased the number, as well as the size of the colonies formed. Morphological
      examination showed that IL-7 affected the progeny developed from CD34+ cells
      stimulated by G-CSF or IL-3, increasing the number of CFU-M (colony forming unit
      macrophage) and CFU-granulocyte-macrophage, whereas the number of CFU-granulocyte
      were unaltered.

PMID- 7519075
TI  - Abnormal response to granulocyte colony-stimulating factor (G-CSF) in canine
      cyclic hematopoiesis is not caused by altered G-CSF receptor expression.
AB  - A decrease in responsiveness to granulocyte colony-stimulating factor (G-CSF) has
      been implicated in the pathophysiology of cyclic hematopoiesis. Using the canine
      model of cyclic neutropenia, we examined the response of neutrophil precursors to
      G-CSF in vitro and G-CSF receptor expression in neutrophils from grey collie dogs
      to determine whether the abnormal response observed to G-CSF in vivo in this
      disorder is present at the level of the progenitor cell and is caused by
      defective G-CSF receptor expression. Bone marrow mononuclear cells from grey
      collie dogs required sevenfold higher G-CSF concentrations than normal dog cells
      to achieve half-maximal colony growth [56 pmol/L v 8 pmol/L). Receptor binding
      assays with 125I-labeled G-CSF and Scatchard analyses of the equilibrium binding
      data were consistent with expression of a single class of high-affinity receptors
      for G-CSF on neutrophils from both normal dogs and grey collies with similar
      receptor numbers (56 to 446 sites/cell v 78 to 199 sites/cell) and binding
      affinities (28 to 206 pmol/L v 84 to 195 pmol/L). Chemical cross-linking studies
      identified a G-CSF binding protein of approximately 120 kD on neutrophils from
      grey collies, similar in size to that on normal dog neutrophils. No abnormal G
      CSF receptor mRNA transcripts were detected in neutrophils from grey collie dogs
      by Northern blot analysis. Treatment of both normal and grey collie neutrophils
      with G-CSF rapidly induced tyrosine phosphorylation of an 80-kD protein that
      behaved like canine c-rel. These results demonstrate that the abnormal
      responsiveness to G-CSF in canine cyclic hematopoiesis is present in neutrophil
      precursors and is not associated with demonstrable alterations in the number,
      binding affinity, or overall size of the G-CSF receptor in neutrophils, or with
      defective tyrosine phosphorylation of p80. These data suggest that cyclic
      hematopoiesis is caused by a defect in the G-CSF signal transduction pathway at a
      point distal to G-CSF receptor binding that does not involve the early
      biochemical events leading to p80 tyrosine phosphorylation.

PMID- 7519076
TI  - Mobilization of long-term hematopoietic reconstituting cells in mice by the
      combination of stem cell factor plus granulocyte colony-stimulating factor.
AB  - In this study, we have compared the ability of recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) alone and the combination of low doses of
      recombinant rat pegylated stem cell factor (rrSCF-PEG) plus rhG-CSF to mobilize
      peripheral blood progenitor cells (PBPCs) with long-term engrafting potential.
      Female recipient irradiated mice were transplanted with PBPCs from male mice that
      were mobilized with rhG-CSF alone (group A) or rrSCF-PEG plus rhG-CSF (group B).
      As previously shown, greater short-term survival resulted in group B compared
      with group A, with 80% and 40% survival at 30 days posttransplant, respectively.
      Both groups of animals showed long-term donor-derived engraftment in greater than
      95% of animals, as determined by quantitative specific polymerase chain reaction
      amplification of a Y chromosome sequence from whole blood of the mice at 6 to 12
      months posttransplantation. Analysis of individual granulocyte-macrophage
      colonies, picked up from semisolid methylcellulose culture of bone marrow cells
      from transplanted mice, resulted in detection of donor-derived DNA in 98% of
      colonies from group B mice compared with 81% from group A mice. These data show
      that cells with long-term potential are mobilized by rhG-CSF alone and the
      combination of rrSCF-PEG plus rhG-CSF. Furthermore, an increased number of cells
      with short-term and long-term engraftment potential was obtained with rrSCF-PEG
      plus rhG-CSF compared with rhG-CSF alone.

PMID- 7519077
TI  - In vivo synergy between recombinant human stem cell factor and recombinant human
      granulocyte colony-stimulating factor in baboons enhanced circulation of
      progenitor cells.
AB  - Recombinant human stem cell factor (rhSCF) and recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) are synergistic in vitro in stimulating the
      proliferation of hematopoietic progenitor cells and their precursors. We examined
      the in vivo synergy of rhSCF with rhG-CSF for stimulating hematopoiesis in vivo
      in baboons. Administration of low-dose (LD) rhSCF (25 micrograms/kg) alone did
      not stimulate changes in circulating WBCs. In comparison, administration of LD
      rhSCF in combination with rhG-CSF at 10 micrograms/kg or 100 micrograms/kg
      stimulated increases in circulating WBCs of multiple types up to twofold higher
      than was stimulated by administration of the same dose of rhG-CSF alone. When the
      dose of rhG-CSF is increased to 250 micrograms/kg, the administration of LD rhSCF
      does not further increase the circulating WBC counts. Administration of LD rhSCF
      in combination with rhG-CSF also stimulated increased circulation of
      hematopoietic progenitors. LD rhSCF alone stimulated less of an increase in
      circulating progenitors, per milliliter of blood, than did administration of rhG
      CSF alone at 100 micrograms/kg. Baboons administered LD rhSCF together with rhG
      CSF at 10, 100, or 250 micrograms/kg had 3.5- to 16-fold higher numbers per
      milliliter of blood of progenitors cells of multiple types, including colony
      forming units granulocyte/macrophage (CFU-GM), burst-forming unit-erythroid (BFU
      E), and colony-forming and burst-forming units-megakaryocyte (CFU-MK and BFU-MK)
      compared with animals given the same dose of rhG-CSF without rhSCF, regardless of
      the rhG-CSF dose. The increased circulation of progenitor cells stimulated by the
      combination of rhSCF plus rhG-CSF was not necessarily directly related to the
      increase in WBCs, as this effect on peripheral blood progenitors was observed
      even at an rhG-CSF dose of 250 micrograms/kg, where coadministration of LD rhSCF
      did not further increase WBC counts. Administration of very-low-dose rhSCF (2.5
      micrograms/kg) with rhG-CSF, 10 micrograms/kg, did not stimulate increases in
      circulating WBCs, but did increase the number of megakaryocyte progenitor cells
      in blood compared with rhG-CSF alone. LD rhSCF administered alone for 7 days
      before rhG-CSF did not result in increased levels of circulating WBCs or
      progenitors compared with rhG-CSF alone. Thus, the synergistic effects of rhSCF
      with rhG-CSF were both dose- and time-dependent. The doses of rhSCF used in these
      studies have been tolerated in vivo in humans.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7519078
TI  - Differential regulation of alpha and beta chains of C4b-binding protein during
      acute-phase response resulting in stable plasma levels of free anticoagulant
      protein S.
AB  - Regulation of C4b-binding protein (C4BP) isoforms during acute phase and its
      relationship to the plasma concentration of free protein S was elucidated. An
      assay for beta chain containing C4BP (C4BP beta+) was developed and the
      concentrations of total C4BP, C4BP beta+, total, free, and bound protein S were
      measured in patients with acute-phase response. Even though total C4BP was
      increased to 162% (mean value) of controls, the corresponding value of C4BP beta+
      was only 122%. In the acute-phase group, total protein S was increased to the
      same extent as C4BP beta+ (mean value of 124%), whereas free protein S was not
      decreased. In controls, total and bound protein S correlated with total C4BP and
      C4BP beta+. However, in the acute-phase group, the correlation between bound
      protein S and total C4BP was lost, although the correlation between C4BP beta+
      and protein S remained. The present results suggest stable levels of free protein
      S during acute phase to be the result of differential regulation of C4BP alpha-
      and beta-chain expression, and the concentration of free protein S to be the
      resulting molar excess of protein S over C4BP beta+. This mechanism ensures
      functional levels of free anticoagulant protein S despite high levels of C4BP.

PMID- 7519079
TI  - Generation of human natural killer cells from immature progenitors does not
      require marrow stromal cells.
AB  - Human natural killer (NK) cells comprise 10% to 15% of peripheral blood
      mononuclear cells and have an important role in immune responses against tumors,
      viral infections, and graft rejection. NK cells originate in bone marrow (BM),
      but their progenitors and lineage development have not been completely
      characterized. We studied the generation of NK cells from purified CD34+HLADR-
      and CD34+HLADR+ BM progenitors and the influence of various cytokines on their
      production. We show that CD3-CD56+ cytotoxic NK cells can develop from both
      progenitors populations when interleukin-2 (IL-2) is present in an in vitro
      suspension culture system containing IL-1 alpha and stem cell factor. Up to 83.8%
      and 98.6% CD3-CD56+ cells were detected in CD34+HLADR- and CD34+DR+ cultures,
      respectively, after 5 weeks of culture; significant numbers of NK cells were
      first detected after 2 weeks. Cytotoxic activity paralleled NK cell numbers; up
      to 70% specific lysis at an effector:target ratio of 10:1 was observed at 5
      weeks. IL-7 also triggered development of CD3-CD56+ cells from these immature
      progenitors (up to 24% and 55% appeared in CD34+HLADR- and CD34+HLADR+ cultures,
      respectively). Our data suggest that BM stromas are not necessary for NK cell
      development and that IL-2 remains essential for this lineage development and
      differentiation.

PMID- 7519080
TI  - Cell surface expression of c-kit receptors by childhood acute myeloid leukemia
      blasts is not of prognostic value: a report from the Childrens Cancer Group.
AB  - The prognostic significance of c-kit receptor expression on leukemic blast cells
      was determined in 122 children with acute myeloid leukemia (AML) entered onto
      Childrens Cancer Group protocol 213. Clinical and laboratory characteristics as
      well as outcome were analyzed according to the percentage of blast cells
      expressing c-kit receptors and the relative number of c-kit receptors per cell as
      determined by indirect immunofluorescence. c-kit receptor expression was strongly
      associated with the expression of the CD34 antigen. However, contrary to findings
      in adult patients with AML, c-kit receptor expression by childhood AML blast
      cells was not predictive of a poor response to therapy.

PMID- 7519081
TI  - CD18-dependent and L-selectin-dependent neutrophil emigration is diminished in
      neonatal rabbits.
AB  - Human neonatal neutrophils manifest decreases in mobility, adherence, and
      emigration compared with adult neutrophils that may contribute to the increased
      susceptibility of neonates to infection. In a developmental rabbit model, we show
      a reduced ability of neutrophils from 1-day-old rabbit pups to emigrate to
      inflamed peritoneium (3.7 +/- 0.35 x 10(6) neutrophils/mL peritoneal exudate)
      compared with 14-day-old (8.5 +/- 0.7 x 10(6)/mL) and adult rabbits (9.4 +/- 1.4
      x 10(6) mL, P < .05) despite significantly increased blood neutrophil counts.
      Because the reductions in functional Mac-1 (CD11b/CD18) as well as the amount of
      surface L-selectin are hypothesized to be primarily responsible for the
      differences in human neonatal neutrophil mobility, we examined CD11b/CD18 and L
      selectin in our model. Using flow cytometric analysis we found that similar to
      human neonates, neutrophils from 1-day-old rabbit pups had 57% of adult rabbit
      levels of L-selectin and, in contrast with adults, failed to show significant
      decreases in L-selectin after chemotactic stimulation. In addition, neutrophils
      from 1-day-old pups compared with adults showed a significantly diminished
      capacity to upregulate CD11b/CD18 after chemotactic stimulation in vitro, or
      after emigration to the inflamed peritoneum. Systemic administration of anti-L
      selectin monoclonal antibody (MoAb) resulted in significant reduction in
      peritoneal neutrophils in adult (47%, P < .05) and 14-day-old rabbits (47%, P <
      .05), but was without effect in 1-day-old rabbits. Administration of anti-CD18
      MoAb resulted in significant reduction in peritoneal neutrophil accumulation in
      all age groups though less in 1 day and 14 day (58% and 65%, respectively) than
      in adults (91%, P < .05). Only in the 14-day-old rabbits was there an additive
      effect of anti-L-selectin and anti-CD18 MoAbs compared with anti-CD18 alone (84%
      v 65%, P < .05). The findings in this in vivo rabbit model support the hypothesis
      that the previously described in vitro defects in human neonatal L-selectin and
      CD11b/CD18 may be major contributors to human neonatal inflammatory deficits.

PMID- 7519082
TI  - Regulation of gastric mucosal calcium channel activity by an antiulcer agent,
      ebrotidine.
AB  - Ebrotidine is a new H2-receptor antagonist also known for its gastroprotective
      effect against ethanol-induced mucosal injury. In this study, we investigated the
      effect of ebrotidine on the activity of the gastric mucosal calcium channels. The
      channel complex was isolated from the solubilized gastric epithelial cell
      membranes by affinity chromatography on wheat germ agglutinin. The complex
      following labeling with [3H] PN200-110 was reconstituted into phosphatidylcholine
      vesicles which exhibited active 45Ca2+ uptake into intravesicular space and
      responded in a concentration-dependent manner to calcium channel activator, BAY
      K8644, as well as to calcium channel antagonist, PN200-100. The 45Ca2+ uptake was
      inhibited by ebrotidine which caused maximum inhibitory effect of 54.9% at 50
      micrograms/ml. The gastric mucosal calcium channels on epidermal growth factor
      binding (EGF) in the presence of ATP responded by an increase in tyrosine
      phosphorylation of 55 and 170 kDa proteins, and the vesicles containing the
      phosphorylated channels displayed a 48% greater 45Ca2+ uptake. This
      phosphorylation process was inhibited by ebrotidine which also interfered with
      the binding of EGF to calcium channel protein. The results point towards the
      importance of EGF in the maintenance of gastric mucosal calcium homeostasis, and
      suggest that ebrotidine has the ability to protect the cellular integrity from
      calcium imbalance by modulating the EGF-stimulated gastic mucosal calcium channel
      phosphorylation.

PMID- 7519083
TI  - Generation of nitric oxide from nitrovasodilators modulates the release of
      histamine from mast cells.
AB  - The effect of organic and inorganic nitrovasodilators (sodium nitroprusside; 3
      morpholinosydnonimine; glyceryl trinitrate; isosorbide dinitrate; sodium nitrite,
      was studied on the release of histamine evoked by compound 48/80 and calcium
      ionophore A 23187 in isolated purified rat serosal mast cells. All the compounds
      tested were capable of significantly reducing the release of histamine in a
      concentration-dependent fashion, at different levels of potency. This effect was
      reverted by oxyhaemoglobin. The inhibitory effect of glyceryl trinitrate on the
      release of histamine was potentiated in cells taken from animals pretreated with
      Escherichia coli lipopolysaccharide, and decreased by NG-nitro-L-arginine methyl
      ester. Glyceryl trinitrate and isosorbide dinitrate concentration-dependently
      increase the generation of nitric oxide by rat serosal mast cells. The inhibitory
      effect of glyceryl trinitrate and isosorbide dinitrate on the release of
      histamine from mast cells was potentiated by N-acetylcysteine, which
      significantly increases the generation of nitric oxide by mast cells. It is
      concluded that nitrovasodilators inhibit the release of mast cell histamine
      through the generation of nitric oxide. The effect may be relevant in considering
      the perivascular location of mast cells and the role played by these cells in
      cardiovascular pathophysiology.

PMID- 7519084
TI  - Carboxyebselen a potent and selective inhibitor of endothelial nitric oxide
      synthase.
AB  - Ebselen (Ebs) a glutathione peroxidase like agent has been recently described as
      an inhibitor of nitric oxide synthase (NOS). Presently, we report that
      carboxyebselen (HOOC-Ebs), a hydrophyllic derivative of Ebs inhibits NOS present
      in enzymatic preparations from bovine endothelium, porcine cerebella, and murine
      spleen, however, it is both more potent and more selective for the constitutive
      endothelial NOS than Ebs. Unlike Ebs, HOOC-Ebs (0.1-30 microM) causes a
      concentration-dependent endothelium-independent relaxations of rings of rabbit
      aorta. The mechanism of this relaxation remains unknown and it is attenuated by
      glutathione (GSH, 30-300 microM) and N-acetyl-L-cysteine (NAC, 30-300 microM).
      The vasorelaxant activity of acetylcholine (Ach, 0.1-1 microM) in aortic rings
      exposed to low concentrations of HOOC-Ebs (0.1-1 microM) or rings exposed to 10
      microM HOOC-Ebs after their pretreatment with GSH or NAC (30-300 microM) remained
      unchanged. The lack of activity of HOOC-Ebs as a NOS inhibitor in intact
      endothelial cells contrasts the effectiveness of Ebs in this respect.

PMID- 7519086
TI  - Prevention of postoperative thromboembolism in general surgery with enoxaparin.

PMID- 7519085
TI  - Bleeding effects of unfractionated heparin and low molecular weight heparins in
      an animal model.

PMID- 7519087
TI  - Comparison of enoxaparin versus unfractionated heparin in general surgery. SURGEX
      Study Group.

PMID- 7519088
TI  - Antithromboembolic efficacy and safety of enoxaparin in general surgery. German
      multicentre trial.

PMID- 7519089
TI  - Clinical profile of enoxaparin in a high-risk situation.

PMID- 7519090
TI  - Cost-effectiveness of venous thromboembolism prophylaxis in surgery.

PMID- 7519091
TI  - Different levels of risk in surgery.

PMID- 7519092
TI  - Low molecular weight heparin: laboratory properties and clinical evaluation. A
      review.

PMID- 7519093
TI  - [Clinical and experimental study of benign prostatic hyperplasia with
      intraglandular injection of chuan shen tong].
AB  - 1038 cases of benign prostatic hyperplasia (BPH) were treated by injection of
      Chuan Shen Tong (CST), a Chinese herbal medicine, into the prostate gland. At the
      end of treatment the effective rate was 96%. After the treatment the BPH with
      urodynamic measurement was studied and it was found that the peak flow rate and
      mean flow rate increased 18% and 41.8% respectively. Transabdominal and
      transrectal ultrasonographies were used to measure the shrinkage of prostate's
      size after the injection treatment to be 0.51 and 0.4 cm (mean diameter)
      respectively. Animal model of BPH was established by the testosterone propionate.
      The prostatic weight and prostatic index was measured in mice after the injection
      of CST, it significantly decreased compared with that of the control (P < 0.01).
      The pathological findings: The hyperplastic papillae disappeared and the body of
      prostate markedly shrank in size. Experiment dogs has been carried out for the
      prostate quantitative analysis. The result revealed that the prostate parenchyma
      and intercellular substance shrank to 26.8% and 4.5% respectively.

PMID- 7519095
TI  - Macronuclear DNA demethylation is involved in the encystment process of the
      ciliate Colpoda inflata.
AB  - Ciliate encystment is an eukaryotic cell differentiation process which involves a
      specific gene expression, to form the resting stage. In this study, we
      investigate, for first time, the DNA methylation pattern changes during
      encystment in the ciliate Colpoda inflata, and the 5-azacytidine effect on
      growing cells and encystment. Results indicate that 5-methylcytosine is present
      in macronuclear DNA of this ciliate and the 5-azacytidine treatment induces
      encystment in growth conditions. From restriction enzyme digestion and 5
      azacytidine experiments, we conclude that a specific DNA demethylation is
      probably involved in the encystment gene expression of this ciliate.

PMID- 7519094
TI  - Childhood abuse and neglect and loss of self-regulation.
AB  - Secure attachments with caregivers play a critical role in helping children
      develop a capacity to modulate physiological arousal. Loss of ability to regulate
      the intensity of feelings and impulses is possibly the most far-reaching effect
      of trauma and neglect. It has been shown that most abused and neglected children
      develop disorganized attachment patterns. The inability to modulate emotions
      gives rise to a range of behaviors that are best understood as attempts at self
      regulation. These include aggression against others, self-destructive behavior,
      eating disorders, and substance abuse. The capacity to regulate internal states
      affects both self-definition and one's attitude toward one's surroundings. Abused
      children often fail to develop the capacity to express specific and
      differentiated emotions: Their difficulty putting feelings into words interferes
      with flexible response strategies and promotes acting out. Usually, these
      behaviors coexist, which further complicates diagnosis and treatment. Affective
      dysregulation can be mitigated by safe attachments, secure meaning schemes, and
      pharmacological interventions that enhance the predictability of somatic
      responses to stress. The ability to create symbolic representations of terrifying
      experiences promotes taming of terror and desomatization of traumatic memories.

PMID- 7519096
TI  - Patient education for endoscopy.
AB  - An increasing number of physicians are considering laparoscopy to be a viable
      alternative to conventional procedures. To meet the complex educational needs of
      the patient, health care providers must continually update their assessment and
      communication skills. This article discusses methods are tools to be used in
      providing procedure-specific patient education for endoscopic procedures.

PMID- 7519097
TI  - Phosrestin I, an arrestin homolog that undergoes light-induced phosphorylation in
      dipteran photoreceptors.
AB  - Two classes of phosphorylated homologs of vertebrate arrestins, designated
      phosrestins I (PRI) and phosrestin II (PRII), are expressed in the photoreceptors
      of a fruit fly, Drosophila melanogaster. This study presents evidence that the
      housefly, Musca domestica, also has a protein similar to Drosophila PRI. Our
      conclusion is based on the following evidence. (1) We identified a Musca
      photoreceptor protein exhibiting a molecular mass (51 kDa) and an isoelectric
      point (pI = 8.6) similar to those of Drosophila PRI. This Musca protein,
      designated Musca PRI, changes its pI upon illumination in vivo. Drosophila PRI.
      This Musca protein, designated Musca PRI, changes its pI upon illumination in
      vivo. (2) Rabbit antibodies raised against Musca PRI, against bovine arrestin,
      and against a synthetic peptide based on the Drosophila PRI sequence stained the
      Drosophila and Musca PRIs specifically on 1 and 2-dimensional Western
      immunoblots. (3) Both Drosophila and Musca PRIs incorporated 32P-radioactivity
      from gamma-32P-ATP in cell-free homogenates of retinas. Partial peptide
      digestions of Drosophila and Musca PRIs revealed similarity between these
      proteins. We observed that Drosophila PRI exists in the random preparation, but
      it also exists in other subcellular fractions. Immunocytochemistry at the EM
      level revealed a distribution of both Drosophila and Musca PRI epitopes in
      membranous vesicular structures in the cytosol as well as in the rhabdomeric
      microvillar membranes where the visual pigment, rhodopsin, exists. Such
      distribution of PRI epitopes suggests that PRI and its light-dependent
      phosphorylation may function in a space remote from the rhabdomere as well as the
      immediate milieu of photoreception.

PMID- 7519098
TI  - Dietary control of late trypsin gene transcription in Aedes aegypti.
AB  - In Aedes aegypti the levels of midgut trypsin activity after feeding are directly
      proportional to the protein concentration in the meal. The mechanisms of this up
      regulatory event were investigated by analyzing the expression of the late
      trypsin gene under different dietary conditions. Transcription of the gene was
      dependent on both the quality and quantity of protein in the meal. As measured by
      Northern blot analysis, the levels of late trypsin gene expression increased up
      to 100-fold 24 h after feeding on gamma-globulin, hemoglobin or albumin (100
      mg/ml). In contrast, gelatin, histone, amino acids, saline or agarose were very
      poor inducers of transcription. The rates of late trypsin transcription induced
      during the first 24 h were directly proportional to the concentration of protein
      in the meal. These data further support the suggestion that the primary mechanism
      that regulates the synthesis of trypsin in the mosquito midgut is transcriptional
      regulation of the gene. This regulatory mechanism enables the midgut to maintain
      the appropriate balance between protease synthesis and the protein content of the
      meal.

PMID- 7519099
TI  - [The treatment of stage I malignant non-seminoma tumors of the testis without
      systematic lumbo-aortic dissection. Results of a study begun 20 years ago.
      Apropos of 21 cases].
AB  - Over a 20-year period (1971-1991), the authors have treated 75 malignant
      testicular tumours, corresponding to 33 seminomas and 42 nonseminomatous tumours.
      The latter group included 23 stage I tumours according to Peckham's
      classification. The authors studied the therapeutic modalities of 21 of these
      patgients (2 non-protocol patients excluded) treated without lumboaortic lymph
      node dissection. Adjuvant therapy consisted of radiotherapy alone (2 cases),
      radiotherapy and chemotherapy (5 cases) and chemotherapy alone (14 cases). All
      patients are alive in complete remission (100%) with a follow-up of at least 24
      months (range: 31-222 months, mean survival: 102.2 months). In line with what
      they already believed in 1971, the authors consider that systematic lumboaortic
      lymph node dissection is not essential in the treatment of stage I
      nonseminomatous testicular tumours, but propose systematic adjuvant therapy.
      Chemotherapy (PVB or, preferably, PEB) provides a guarantee of security and good
      acceptability.

PMID- 7519100
TI  - [A modified cervico-prostatic incision technic in hypertrophic adenoma in young
      subjects desiring to preserve ejaculation].
AB  - The treatment of bladder neck obstruction by transurethral resection of the
      prostate is responsible for retrograde ejaculation, which is poorly tolerated by
      our younger patients. Bladder neck incision, initially proposed as treatment for
      bladder neck sclerosis and for small prostates, was performed according to a
      modified technique in 36 patients with a mean age of 57.6 years (range: 41-72
      years), with benign prostatic hypertrophy less than 30 grams and wishing to
      retain antegrade ejaculation. This technique consists of creating a deep groove
      with the resector hook extending from the ureteric orifice to 5 mm above the
      verumontanum, incising the full thickness of the detrusor and prostatic urethra
      as far as the retrocervical fat. This preserves a supramontanal ring of urethral
      muscle whose contraction during orgasm prevents retrograde ejaculation of semen.
      Resection of the median lobe was also performed in 8 patients, while sparing the
      cervical muscular ring. The mean follow-up was 2.4 years (range: 4-84 months).
      Dysuria was very considerably improved in 32 patients (91.5%), with a Madsen
      score of less than 2. Antegrade ejaculation was preserved in 32 patients (91.5%).
      Two patients had to undergo secondary prostatic resection because of persistent
      dysuria (these 2 patients retained antegrade ejaculation). Unilateral bladder
      neck incision, sparing a supramontanal muscular ring is an easy, rapid technique
      with low morbidity, effective in the treatment of prostatism due to a small
      prostate (less than 30 grams). It is the operation of choice in young patients
      with small prostates who wish to retain antegrade ejaculation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7519101
TI  - Diarrhetic shellfish poisoning associated with mussels.

PMID- 7519102
TI  - Reference values and hematologic changes from birth to 5 years in patients with
      sickle cell disease. Cooperative Study of Sickle Cell Disease.
AB  - OBJECTIVE: To examine hematologic changes from birth to 5 years of age and
      establish hematologic reference values for infants and children with sickle cell
      disease. RESEARCH DESIGN: Prospective natural history study. SETTING: Nineteen
      pediatric sickle cell centers across the United States. PATIENTS: Six hundred
      ninety-four infants with sickle cell disease (sickle cell anemia, sickle cell
      hemoglobin C disease, and sickle-beta-thalassemia) who were enrolled in the
      Cooperative Study of Sickle Cell Disease at younger than 6 months of age. Median
      follow-up time through 5 years of age was 4.1 years. MEASUREMENTS AND RESULTS: We
      present longitudinal analyses of total hemoglobin concentration, percent fetal
      hemoglobin values, mean corpuscular volumes, total bilirubin concentration, and
      red blood cell (RBC), "pocked" RBC, white blood cell, platelet, and reticulocyte
      counts. Anemia was apparent by 10 weeks of life in infants with sickle cell
      anemia (SS infants). This anemia was associated with a rising reticulocyte count
      consistent with a hemolytic process. The reticulocyte count of SS infants
      increased steadily, exceeding 12% at 5 years of age. The fetal hemoglobin
      concentration of SS infants declined more slowly than that of infants with sickle
      cell hemoglobin C disease (SC infants). Pocked RBC counts rose sharply after 6
      months of age, and by 1 year, 28% of SS infants had abnormal counts, above 3.5%,
      indicating poor splenic function. At 3 years of age, 78% of SS patients and 32%
      of SC patients had abnormal pocked RBC counts. The SS patients with concurrent
      alpha-thalassemia had, after 6 months of age and throughout early childhood, a
      slightly higher mean total hemoglobin concentration and lower mean pocked RBC and
      reticulocyte counts than SS patients without alpha-thalassemia. The hematologic
      profile of SC infants more closely resembled that of normal black infants, but
      there was mild anemia (10.5 g/dL) and slightly elevated mean values for
      reticulocytes (3%) and fetal hemoglobin (3%) during early childhood.

PMID- 7519104
TI  - Morphological aspects of LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways in human
      lymph nodes.
AB  - Monoclonal antibodies specific for the adhesion molecules participating in
      lymphocyte homing, lymphocyte function associated antigen-1 (LFA-1) and very late
      antigen 4 (VLA4), and their respective ligands, intercellular adhesion molecule 1
      (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), were used to
      characterize their expression pattern in human lymph nodes by immunohistochemical
      and immunoelectron microscopic techniques. The location of LFA-1-positive
      lymphocytes and selective expression of ICAM-1 on the luminal plasma membrane of
      high endothelial venule endothelium suggested that the LFA-1/ICAM-1 adhesion
      pathway participates only in the initial step of the lymphocyte migration
      process. Lymphocytes passing through endothelium appear not to be influenced by
      this pathway. VCAM-1 was detected occasionally on the endothelium of high
      endothelial venules in the hyperplastic lymph nodes in the mesentery, but not in
      peripheral lymph nodes. VLA4-positive lymphocytes tended to be more frequently
      observed within high endothelial venules in mesenteric lymph nodes than in
      peripheral ones. Strong expression of both ligands, ICAM-1 and VCAM-1, was noted
      on the plasma membrane of follicular dendritic cells, and was especially
      prominent on their labyrinthine folding, and on the interdigitating cells in the
      paracortex. Furthermore, both LFA-1- and VLA4-positive lymphocytes localized
      around these cells. This suggests that LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion
      pathways play an important role in the lymphocyte recognition of antigen
      presenting cells.

PMID- 7519103
TI  - Possible nosocomial transmission of Pseudomonas cepacia in patients with cystic
      fibrosis.
AB  - OBJECTIVE: To determine whether nosocomial transmission of Pseudomonas cepacia
      occurred at a hospital with endemic P cepacia infection of patients with cystic
      fibrosis. DESIGN: Two retrospective case-control studies. SETTING: A large
      pediatric cystic fibrosis center. PARTICIPANTS: To assess risk factors for
      acquisition of P cepacia, 18 cases, defined as any patient with cystic fibrosis
      with first documented isolation of P cepacia in 1988 or 1989, were compared with
      18 matched P cepacia-negative controls with cystic fibrosis. To assess potential
      modes of nosocomial P cepacia transmission, 14 cases with a hospitalization(s)
      between their last P cepacia-negative culture and first P cepacia-positive
      culture were compared with 14 hospitalized P cepacia-negative controls with
      cystic fibrosis. METHODS: Handwiping cultures (N = 68) and selective
      environmental cultures were performed. MAIN RESULTS: Cases tended to be more
      likely than controls to have been hospitalized at the cystic fibrosis center in
      the 3 months before their first P cepacia-positive culture (P = .08). In
      addition, cases tended to be more likely than hospitalized controls with cystic
      fibrosis to have had a P cepacia-positive roommate (P = .06) before becoming
      colonized with P cepacia organisms. Pseudomonas cepacia was cultured from the
      hands of two individuals: a P cepacia-colonized patient who had just undergone
      chest physiotherapy and consequent coughing and the investigator who shook the P
      cepacia-positive patient's hand after the patient's procedure. CONCLUSIONS: These
      results suggest that in this cystic fibrosis center, hospitalization is a risk
      factor for P cepacia acquisition and that person-to-person transmission of P
      cepacia may occur in the hospital via hand contact.

PMID- 7519105
TI  - Progressive activity in latent prostate carcinoma defined by argyrophilic
      staining of the nucleolar organizer regions (AgNOR).
AB  - Argyrophilic staining of the nucleolar organizer regions (AgNOR) was studied in
      30 cases of benign prostatic hyperplasias (BPH), 17 cases of latent prostate
      carcinomas, 50 cases of clinical carcinomas and seven cases of metastatic lesions
      from prostate carcinomas. The criteria for these comparisons were the number of
      positive-staining dots per nucleus, the area of the dots, and a relative score
      determined by multiplying the number of positive-staining dots in the nuclei by
      the areas of the dots. Overall, there were no significant differences in these
      three parameters between BPH and latent carcinomas. Among latent carcinomas,
      however, significantly higher AgNOR scores were observed for infiltrative lesions
      than for non-infiltrative lesions. AgNOR dot number, area and score increased as
      tumors became less differentiated, with no significant differences detected in
      metastatic versus non-metastatic carcinomas. These results suggest that some
      latent tumors are similar in biological behavior, such as cell proliferation, to
      clinical carcinoma.

PMID- 7519107
TI  - The clinical use of flow cytometry for assessing platelet activation in acute
      coronary syndromes. TIMI-III Thrombosis and Anticoagulation Group.
AB  - BACKGROUND: Unstable angina signals a sudden transition from stable to unstable
      atherosclerotic coronary artery disease. Although assessment of platelet activity
      has been shown to provide diagnostic and prognostic information, most available
      methods lack sufficient sensitivity or specificity for them to be useful in
      clinical practice. In recent years, fluorescently labeled antibodies and flow
      cytometry have permitted the detection of activation proteins on individual
      platelets. The purpose of the present study was to assess the ability of flow
      cytometry to detect platelet activation in patients with unstable angina and non
      Q-wave myocardial infarction. METHODS: Platelet activation before treatment was
      determined from whole-blood samples in 19 patients participating in the
      Thrombolysis in Myocardial Ischemia (TIMI)-IIIB study and in nine healthy
      volunteers (total of 24 samples) using flow cytometry and a monoclonal antibody
      (clone 1E3) to the activation-dependent, surface-expressed protein P-Selectin.
      RESULTS: Among healthy volunteers, a small percentage of platelets were activated
      (2.0 +/- 2.5%). In contrast, 15 out of 19 (79%) patients with suspected
      myocardial ischemia at rest had 10.4 +/- 11.1% activated platelets (95%
      confidence interval 4.9-15.9%; P < 0.01). Seven patients (37%) were found to have
      more than 10% activated platelets. The degree of platelet activation did not
      differ significantly between patients with unstable angina and those with
      elevated creatine kinase levels (non-Q-wave myocardial infarction). CONCLUSION:
      Whole-blood flow cytometric techniques can minimize the artifactual platelet
      activation often seen with other techniques and therefore offer distinct
      advantages in the investigation of patients with thrombotic coronary syndromes.
      In TIMI-III, patients with unstable angina and non-Q-wave myocardial infarction
      had clear evidence of platelet activation. An ongoing study will examine the
      correlation between platelet activation assessed using flow cytometry and
      clinical events in a larger patient cohort.

PMID- 7519106
TI  - Chromophobe renal cell carcinoma: a report of two cases.
AB  - Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC,
      which has rarely been reported in Japan. In this communication, the authors
      report two Japanese cases of chromophobe RCC together with the
      immunohistochemical findings. The tumors were composed of sheets and cribriform
      glands formed by tumor cells with cloudy and reticular cytoplasm.
      Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The
      tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm
      Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin
      was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more
      frequent than that to Lotus tetragonolobus agglutinin. The results of this study
      suggest that the tumor cells possessed phenotypes similar to the distal nephron
      rather than to the proximal tubular cells.

PMID- 7519108
TI  - Assessment of the cytokine response in liver donors at the time of organ
      procurement and association with allograft function after orthotopic
      transplantation.
AB  - BACKGROUND: The cause of allograft liver dysfunction after transplantation is
      unresolved. We tested the hypothesis that human donor liver may be predisposed to
      ischemia reperfusion injury, and graft dysfunction subsequent to ongoing
      inflammatory processes during donor hospitalization. STUDY DESIGN: A prospective
      study of organ donors and transplant recipients of allograft livers from these
      donors was conducted. Portal venous, inferior vena caval, and superior vena caval
      blood samples were obtained from 16 clinical organ donors at the time of organ
      procurement (one to 12 days post-trauma) to characterize the hepatic cytokine and
      acute phase protein response, to determine whether or not this response resulted
      from bacterial or endotoxin translocation to the portal circulation, and to
      assess whether or not transplant outcome was associated with plasma levels of
      cytokines in the donor. RESULTS: In comparison with systemic blood samples from
      ten healthy persons, all 16 donors exhibited significantly (p < 0.05) elevated
      plasma concentrations of interleukin-6, interleukin-8, soluble p55 tumor necrosis
      factor receptor type I (sTNFr-I), and C-reactive protein. No concentration
      differences existed among portal venous, inferior vena caval, and superior vena
      caval blood samples for any cytokine or acute phase protein measured. Donor
      levels of endotoxin, TNF-alpha, soluble intercellular adhesion molecule-1 (sICAM
      1), alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobin were
      comparable with those in the healthy persons. Bacterial cultures of portal blood
      were negative. There was no association between the causation of donor trauma and
      either donor cytokine response or function and quality of the allograft liver
      after transplantation. Nor could an association between donor cytokine response
      and either early allograft function (less than 96 hours) or eventual transplant
      outcome in the recipients be detected. CONCLUSIONS: These results indicate that,
      although an ongoing inflammatory response to injury was evident in these donors
      at the time of organ procurement, there were no apparent adverse effects arising
      from these inflammatory processes on the function and quality of the donor liver
      after transplantation. Bacterial translocation does not seem to be a component of
      the pathogenesis of inflammation. Whether or not the presence of inflammation in
      the donor alters the metabolic responses of the allograft liver and recipient to
      transplant operation is unknown.

PMID- 7519109
TI  - Ictal verbal behaviour: a review.
AB  - An overview is given of the various disturbances which epileptic seizures without
      loss of consciousness may cause in the patient's voluntary verbal behaviour, as
      well as of the unintentional verbal activities which seizures may induce. It is
      shown that during seizures, patients may preserve their verbal skills, or lose
      them in part or completely. They may also show undeliberate verbal behaviours, of
      which they may or may not be conscious.

PMID- 7519110
TI  - The pathophysiological changes in the bladder obstructed by benign prostatic
      hyperplasia.

PMID- 7519111
TI  - A new, large calibre, self-expanding and self-retaining temporary intraprostatic
      stent (ProstaCoil) in the treatment of prostatic obstruction.
AB  - OBJECTIVE: To determine the benefits of a new self-expanding and self-retaining
      large calibre temporary intraprostatic coil stent in patients with bladder
      outflow obstruction due to benign prostatic hypertrophy. PATIENTS AND METHODS:
      Sixty-five patients with bladder outflow obstruction have been studied with a
      follow-up period of 3-28 months (mean 16). RESULTS: Thirty patients became
      eligible for surgery and had their stent removed without difficulty 3-12 months
      after stent insertion. Only one stent was removed because of urgency and
      incontinence. Stent repositioning was required in five patients and 14 complained
      of temporary dysuria or perineal pain. Twenty-seven patients continue to pass
      urine through their stent without difficulty. CONCLUSION: Because of its large
      diameter and its temporary nature this new stent allows endoscopic examination of
      the bladder and has few side effects. This stent should be considered as an
      alternative to a urethral catheter or other temporary stents in patients who are
      unfit for surgery.

PMID- 7519112
TI  - A three month double-blind study of doxazosin as treatment for benign prostatic
      bladder outlet obstruction.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of doxazosin in the
      treatment of bladder outflow obstruction resulting from benign prostatic
      hyperplasia (BPH). PATIENTS AND METHODS: One-hundred and thirty-five patients
      with symptomatic urodynamically confirmed obstructive BPH were treated for 12
      weeks with either doxazosin (67 patients) or placebo (68 patients) after an
      initial 2 week baseline evaluation. The main outcome measures were urodynamic and
      symptomatic evaluation for efficacy. Blood pressure and adverse events were
      monitored. RESULTS: Data were obtained in 122 patients (60 doxazosin, 62
      placebo). Doxazosin produced increases in both mean and maximum urinary flow
      rates of 1.01 ml/s and 3.2 ml/s respectively, compared with 0.21 ml/s and 2.2
      ml/s on placebo. The increase in mean flow rate was statistically significant (P
      = 0.04), while that for maximum flow rate approached significance (P = 0.09). The
      maximum subtracted voiding pressure was substantially reduced (P = 0.007) and 19
      of 53 (36%) patients had an increase in maximum flow rate of 50% or more compared
      with 9 of 54 (17%) on placebo (P = 0.024). Twelve weeks' therapy with doxazosin
      resulted in significant improvements (compared with placebo) in: hesitancy
      (doxazosin 26 of 46, placebo 11 of 43; P = 0.003), impaired urinary stream
      (doxazosin 31 of 55, placebo 16 of 48; P = 0.019) nocturia (doxazosin 22 of 56,
      placebo 10 of 54; P = 0.017) and urgency (doxazosin 27 of 45, placebo 16 of 42; P
      = 0.041). Frequency improved with doxazosin therapy (doxazosin 26 of 59, placebo
      15 of 55; P = 0.062). Adverse events, most frequently dizziness and headache,
      were usually mild and transient and led to a discontinuation of doxazosin therapy
      in one patient. No clinically significant changes in sexual function or blood
      pressure were seen. CONCLUSION: Doxazosin was well-tolerated and produced both
      urodynamic and symptomatic improvement in men with BPH, thereby providing a
      satisfactory alternative to existing drugs with the additional benefit of once
      daily dosage.

PMID- 7519113
TI  - The anatomy of a prostate waiting list: a prospective study of 132 consecutive
      patients.
AB  - OBJECTIVE: To report the results of a standard evaluation programme performed
      prior to transurethral resection of the prostate (TURP) for benign prostatic
      hypertrophy (BPH). PATIENTS AND METHODS: All 132 patients with symptoms of
      prostatism on the waiting list for surgery were invited to attend the hospital to
      undergo a physical examination, symptom evaluation and routine blood sampling. Of
      these, 117 attended. If the suspicion of BPH was sustained a transrectal
      ultrasound examination of the prostate and a urodynamic evaluation, including a
      pressure-flow study, were performed. RESULTS: Urodynamic evaluation was carried
      out in 80 of the 117 patients who attended the clinic. Infravesical obstruction
      was present in 61 patients while in 19 (24%) there was no obstruction. An
      operative procedure to relieve obstruction was performed in 65 patients (49%).
      CONCLUSIONS: In a population of patients scheduled for TURP, 24% were found not
      to have an obstruction. This is in accordance with other reports. As the patients
      with few symptoms and those who did not have an obstruction were treated
      conservatively only 49% of the referred cases underwent prostatic surgery.

PMID- 7519114
TI  - Early catheter removal following transurethral prostatectomy--impact on length of
      hospital stay.
AB  - OBJECTIVE: To investigate whether early catheter removal following transurethral
      prostatectomy (TURP) is safe and whether it has any effect on the length of
      hospital stay. PATIENTS AND METHODS: Following transurethral prostatectomy 59
      patients were randomized into one of two groups: those whose catheter was removed
      on day 1 after surgery and those whose catheter was removed on day 2. The
      incidence of complications and the duration of post-operative hospital stay were
      assessed. RESULTS: Catheter removal on day 1 led to a significantly shorter post
      operative hospital stay (2.3 days versus 3.3 days) and did not incur a higher
      incidence of complications. CONCLUSIONS: Removal of the catheter on the first day
      following TURP is safe in selected patients and leads to a shorter post-operative
      hospital stay.

PMID- 7519115
TI  - Screening for carcinoma of the prostate: a GP based study.
AB  - OBJECTIVE: To examine the feasibility and acceptability of screening for cancer
      of the prostate by digital rectal examination (DRE), prostate specific antigen
      (PSA) determination and subsequent transrectal ultrasound (TRUS) in selected
      patients in a single general practice in Hertfordshire. SUBJECTS AND METHODS: A
      total of 568 of 856 men aged 55 to 70 accepted an invitation for a health check
      which included screening for prostate cancer. Of these, 80 individuals with
      either a raised PSA level or an abnormal DRE underwent TRUS. In 29 individuals
      biopsies were taken, 11 of which confirmed the presence of adenocarcinoma of the
      prostate giving an overall detected prevalence of 2%. Of the 11 tumours
      identified by screening, two were T1M0, four were T2M0, two were T3M0 and three
      were T3M1. RESULTS: To assess the acceptability of the screening exercise a
      postal questionnaire was sent to all 568 participants: 83% replied and 69%
      reported no concern. Of the 67 individuals who had undergone TRUS, 69% reported
      discomfort. A total of 448 (95%) of respondents declared that they would be
      prepared to undergo the screening exercise again. CONCLUSION: Screening for
      prostate cancer would seem to be technically feasible and generally acceptable.
      However, there is a considerable false positive rate in the PSA range 4 ng/ml to
      10 ng/ml, particularly among men with clinical evidence of benign prostatic
      hyperplasia. To establish the true benefit of screening a large-scale prospective
      controlled study will be necessary.

PMID- 7519117
TI  - A pragmatic approach to neurolinguistics: requests (re)considered.
AB  - In recent years there has been a series of studies in the field of
      neurolinguistics and neuropsychology investigating the comprehension and
      interpretation of indirect requests predominantly in right brain-damaged
      individuals. Although the findings of these studies seem to suggest that indirect
      requests may be perceived, comprehended, judged, or interpreted differently by
      some right brain-damaged individuals, until today no coherent picture pertaining
      to the description of the phenomenon under investigation has emerged. One reason
      for this dissatisfying situation may be that the features contributing to the
      interpretation of a request in terms of its level of directness have not been
      sufficiently investigated. In addition, the stimuli on which the experiments were
      based are not always clear-cut or specific if viewed within the framework of
      pragmatic theory. The article provides an introduction to some aspects of
      pragmatic theory and discusses five major studies on request comprehension in
      brain-damaged patients with reference to the components relevant to the
      realization of requests. Finally, suggestions concerning future research are
      made.

PMID- 7519118
TI  - Trans-activation of the 5' to 3' viral DNA strand transfer by nucleocapsid
      protein during reverse transcription of HIV1 RNA.
AB  - Two DNA strand transfer reactions take place during reverse transcription of the
      retroviral genome. The first transfer, that of the minus-strand strong stop DNA
      from the 5' end of the viral RNA to the 3' end, has been studied in vitro with
      two RNAs mimicking the 5' and 3' regions of the HIV1 genome and with nucleocapsid
      protein, NCp7, and reverse transcriptase. The results show that NCp7 strongly
      activates the 5' to 3' DNA strand transfer during reverse transcription while a
      basic peptide resembling NCp7 is inactive. Activation of the first transfer by
      several NCp7 derived peptides and the influence of the terminal redundancies (R)
      present at the 5' and 3' ends of HIV1 RNA were also examined. The first transfer
      is optimal in the presence of intact NCp7 and necessitates R on both the 5' and
      3' RNAs. Sequencing of full length viral DNA products reveals approximately 40%
      misincorporations at the first nucleotide beyond the transfer point. If such base
      misincorporations occur during proviral DNA synthesis with possible homologous
      recombinations it may well contribute to the high level of genetic variability of
      HIV.

PMID- 7519119
TI  - Risperidone-induced priapism.

PMID- 7519116
TI  - Detection of microscopic extracapsular extension prior to radical prostatectomy
      for clinically localized prostate cancer.
AB  - OBJECTIVE: To assess better techniques of clinical staging to identify the
      presence and location of extracapsular extension (ECE) and assist the surgeon in
      the selection of candidates for resection or preservation of neurovascular
      bundles during radical prostatectomy. PATIENTS AND METHODS: In a retrospective
      review of the records of 117 patients with clinically localized (31 T1 and 86 T2)
      prostate cancer treated with radical prostatectomy the results of digital rectal
      examination (DRE), real-time transrectal ultrasound (TRUS) and a retrospective
      review of static films were compared to assess their accuracy in the detection of
      ECE. The ultrasonic criterion for ECE was bulging or irregularity of the boundary
      echo adjacent to a hypoechoic lesion. On DRE, the criterion for ECE was palpable
      bulging of a nodule beyond the normal contour of the prostate. The reference
      standard was the presence and location of ECE in the whole-mount, serially
      sectioned radical prostatectomy specimens. RESULTS: Microscopic ECE was present
      in 64 of the specimens (55%). There was no significant difference between DRE,
      prospective TRUS and retrospective TRUS in the overall accuracy of detection of
      ECE. However, when the results of DRE and TRUS were combined (if either was
      positive the result was considered positive), the positive predictive value (PPV)
      was 79% and the sensitivity (91%), with the overall accuracy increased
      significantly (P < 0.05). CONCLUSION: The presence and precise location of
      microscopic ECE can be determined pre-operatively with reasonable accuracy using
      real-time ultrasound combined with the results of DRE.

PMID- 7519121
TI  - Characterization of cloned class I MHC-restricted, CD8+ anti-Meth A cytotoxic T
      lymphocytes: recognition of an epitope derived from the Meth A gp110 tumor
      rejection antigen.
AB  - Meth A gp110 has been tentatively identified as a tumor rejection antigen.
      Following isolation of a class I major histocompatibility complex (MHC)
      restricted, CD8+ anti-Meth A cytotoxic T-lymphocyte (CTL), we sought to determine
      whether the determinant recognized by this CTL was: (a) functional in tumor
      rejection of Meth A sarcoma; and (b) derived from Meth A gp110. Initially, we
      isolated an anti-Meth A CTL-resistant variant of Meth A sarcoma, Meth A4R, by
      immunoselection. The results of the subsequent analysis of Meth A4R cells showed
      the CTL-defined determinant as having a functional role in transplantation
      rejection of Meth A sarcoma. Walker et al. (Proc. Natl. Acad. Sci. USA, 89: 7915
      7918, 1993) showed that the cationic lipid, N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-
      trimethylammonium-methyl sulfate, mediated delivery of a recombinant glycoprotein
      into the cytosol of target cells, making it available for processing and
      presentation by class I MHC molecules. As a result, the cells were sensitized for
      cytolysis by a class I MHC-restricted CD8+ CTL, which recognized an epitope
      expressed by the glycoprotein. In a similar manner, we treated the SV40
      transformed BALB/c cell line, SVBalb, which is relatively insensitive to
      cytolysis by the anti-Meth A CTL, with Meth A gp110 and N-[1-(2,3
      dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate. The sensitivities of
      the treated cells and control cell lines to the anti-Meth A CTL were then
      examined. The results of these experiments permit us to conclude that the
      determinant recognized by the anti-Meth A CTL line is derived from Meth A gp110.

PMID- 7519120
TI  - Inflammation is responsible for the development of wound-induced tumors in
      chickens infected with Rous sarcoma virus.
AB  - When newly hatched chicks are given injections of Rous sarcoma virus, a tumor
      develops at the site of injection. In spite of the presence of the virus in the
      blood, no other tumors are found distant from the site of inoculation during the
      life span of the animal (4-6 weeks). However, if a wound is made away from the
      primary tumor, a tumor develops at the site of wounding. Work in our laboratory
      showed previously that these wound tumors do not develop as a result of
      metastasis, therefore, factors released upon wounding must contribute to the
      development of the wound tumors. In particular, we showed that transforming
      growth factor (TGF) beta, a growth factor implicated in wound healing, can
      replace wounding in tumor development. However, we also showed that epidermal
      growth factor and TGF-alpha, growth factors that also have roles in wound
      healing, do not induce tumors. To identify the critical event(s) and to determine
      the mechanism involved in wound tumor development, we have continued these
      studies. Here we show that: (a) wound tumor development correlates with the
      presence of circulating virus and inflammation; (b) the virus is present in serum
      and in heterophils of the peripheral blood; (c) cell division at the site of
      wounding precedes the expression of viral proteins; (d) in addition to TGF-beta,
      acidic and basic fibroblast growth factors can also replace wounding in tumor
      development; (e) these three factors (TGF-beta, acidic fibroblast growth factor,
      basic fibroblast growth factor) which promote tumors also induce inflammation,
      whereas epidermal growth factor and TGF-alpha do not; and (f) during the
      inflammatory response, blood vessel leakage occurs as tested by the release of
      fibrinogen into the tissues. To test the possibility that inflammation is the key
      element in the development of these wound tumors, we used beta
      methylprednisolone, an antiinflammatory drug that inhibits inflammation
      (including blood vessel leakage), to determine if wound tumor development could
      be prevented. We found that when inflammation was inhibited, tumors were also
      inhibited; when inflammation could not be stopped, tumors developed as before.
      These results indicate that the effect of wounding on the development of wound
      tumors in Rous sarcoma virus-infected chicks is accomplished through the
      cytokines released by the inflammatory cells at the site of wounding. These
      inflammatory mediators play a critical role in providing the conducive
      environment for oncogene integration and activation, and subsequent development
      of tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7519122
TI  - PML/RAR alpha+ U937 mutant and NB4 cell lines: retinoic acid restores the
      monocytic differentiation response to vitamin D3.
AB  - We have analyzed the differentiation program of a U937 promonocytic leukemia
      clone transduced with the acute promyelocytic leukemia specific PML/RAR alpha
      fusion gene, the expression of which is under the control of the inducible
      metallothionine (MT) I promoter (MTPR9 clone). MTPR9 cells treated with Zn2+
      hence exhibit levels of PML-RAR alpha protein as high as fresh acute
      promyelocytic leukemia blasts. In the absence of Zn2+, i.e., upon low level
      PML/RAR alpha expression, 1,25-dihydroxyvitamin D3 (D3) and particularly D3 plus
      transforming growth factor beta 1 (TGF-beta 1) induced terminal differentiation
      of MTPR9 cells (as observed in "wild-type" U937 cells), on the basis of
      morphology, membrane antigen pattern, and functional criteria. Conversely, in the
      presence of Zn2+, D3 and D3 plus TGF-beta 1 failed to induce terminal
      differentiation, as evaluated by the above parameters. Interestingly, retinoic
      acid (RA) treatment suppresses the differentiation blockade induced by high level
      PML-RAR alpha protein; indeed, Zn(2+)-treated MTPR9 cells incubated with RA plus
      D3 exhibited significant terminal monocytic maturation, comparable to that of
      cells treated with D3 alone or combined with RA in absence of Zn2+. Similar
      observations were made in NB4, a PML-RAR+ human acute leukemic line. As expected
      RA treatment of NB4 cells causes granulocytic differentiation. Interestingly, the
      cell line is only scarcely induced to mature monocytic cells by D3 or D3 plus TGF
      beta 1 treatment, whereas it is effectively induced to monocytic maturation by
      combined treatment with D3 and RA. Accordingly, the rate of NB4 cell
      proliferation is only slightly affected by D3 or D3 plus TGF-beta 1 treatment,
      mildly inhibited by RA, and markedly decreased by D3 plus RA. These results
      indicate that in both U937 and NB4 cells high level PML/RAR alpha expression
      inhibits the monocytic terminal differentiation program triggered by D3 or D3
      plus TGF-beta 1, whereas RA treatment effectively antagonizes this inhibitory PML
      RAR alpha action and restores the D3 differentiative effect.

PMID- 7519123
TI  - Hyaluronan receptors are expressed on human malignant mesothelioma cells but not
      on normal mesothelial cells.
AB  - Hyaluronan-binding sites were demonstrated on the cell surface of three malignant
      mesothelioma cell lines derived from human tumors using either [3H]hyaluronan or
      fluorescein-tagged hyaluronan. No hyaluronan-binding activity was observed on
      normal human mesothelial cells. The absence of hyaluronan receptors on normal
      human mesothelial cells was not due to a down-regulation by endogenously
      synthesized hyaluronan, since no binding sites appeared when the cells were
      cultured under conditions known to suppress hyaluronan synthesis (in starvation
      medium containing either hydrocortisone or n-butyrate) or to degrade endogenously
      synthesized hyaluronan (in the presence of Streptomyces or testicular
      hyaluronidase). The binding of [3H]hyaluronan on mesothelioma cells could be
      partially inhibited by prior incubation of the cells with trypsin, indicating
      that the hyaluronan-binding site is a protein. The binding sites on human
      malignant mesothelioma cells were shown to be saturable with about 54,000
      hyaluronan molecules (M(r) 1.4 x 10(6)) bound per cell with a Kd of 0.3 x 10(-9)
      M. The binding was specific for hyaluronan inasmuch as a number of other
      macromolecules gave negligible inhibition of the binding. High molecular weight
      preparations of hyaluronan inhibited the binding more effectively than low
      molecular weight preparations; hyaluronan oligosaccharides down to a length of
      six monosaccharide units showed competing activity. The hyaluronan receptor
      appeared to be related to CD44 (a cell surface glycoprotein previously suggested
      to function as a hyaluronan receptor) since Hermes-1 monoclonal antibodies which
      inhibit the binding of hyaluronan to CD44 blocked a major part of the binding of
      hyaluronan to the mesothelioma cells. However, there was no strict correlation
      between the hyaluronan-binding activity on the mesothelioma cell lines tested and
      the levels of CD44 molecules on their cell surface, suggesting that only a
      subfraction of the CD44 molecules bound hyaluronan or that other hyaluronan
      binding proteins also exist on those cells. The presence of hyaluronan receptors
      on mesothelioma cells, but not on their normal counterparts, may be of importance
      for the migration of the transformed cells in hyaluronan-enriched matrices and
      for their ability to form metastases.

PMID- 7519124
TI  - Normal human tissues, in addition to some tumors, express multiple different CD44
      isoforms.
AB  - At least 20 different isoforms of the human CD44 lymphocyte-homing
      receptor/hyaluronan receptor have been described to date that arise from the
      differential splicing of up to 10 alternative exons (termed v1-v10) encoding the
      membrane-proximal extracellular domain. Although numerous analyses at the mRNA
      level have indicated tissue-specific expression of CD44 variants, few analyses
      have been performed at the protein level because of limited availability of
      suitable monoclonal antibodies. Recently, however, exon-specific monoclonal
      antibodies have been generated using bacterial fusion proteins, and these have
      been reported to detect high levels of vCD44 containing the v6 exon on human
      tumors. Together with earlier evidence linking this particular exon with tumor
      metastasis in the rat, these latter experiments have led to the interpretation
      that v6 splice variants play a causative role in tumor dissemination. In this
      paper we describe the use of a new and comprehensive panel of CD44 exon-specific
      monoclonal antibodies generated against a recombinant CD44(v3-10)-immunoglobulin
      chimera to study vCD44 expression in a large number of normal and neoplastic
      tissues. We show that the expression of vCD44 varies greatly among different
      human tumors and that some express either very low levels of vCD44 or no CD44 at
      all. Furthermore, we demonstrate that expression is not limited to isoforms
      containing the v6 exon but includes variants carrying v3, v4/5, and v8/9.
      Additionally, normal epithelial tissues are shown to express considerable levels
      of these same vCD44 isoforms. Such results argue against a ubiquitous role for
      vCD44 isoforms in promoting tumor growth and metastasis.

PMID- 7519125
TI  - Generation of specific anti-melanoma reactivity by stimulation of human tumor
      infiltrating lymphocytes with MAGE-1 synthetic peptide.
AB  - The MAGE-1 gene encodes a tumor-specific antigen, MZ2-E, which is recognized by
      cloned, specific cytolytic T cells (CTL) derived from the peripheral blood of a
      patient with melanoma. We have produced a MAGE-1-specific CTL line derived from
      the tumor-infiltrating lymphocytes (TIL) of a melanoma patient by weekly
      restimulation with autologous EBV-B cells pulsed with the synthetic HLA-A1
      restricted MAGE-1 epitope nonapeptide EADPTGHSY. The 1277.A TIL line grew in long
      term culture in low-dose interleukin-2 (IL-2) and IL-4, and exhibited antigen
      specific, MHC-class-I-restricted lysis of HLA-A1-bearing MAGE-1+ cell lines.
      Cytolysis of target cells pulsed with the synthetic MAGE-1 decapeptide KEADPTGHSY
      was superior to that of cells pulsed with the immunodominant nonapeptide. Single
      amino-acid or even side-chain substitutions in the immunodominant nonamer
      abrogated cytolysis. 1277.A TIL specifically secreted tumor necrosis factor alpha
      after co-incubation with HLA-A1-expressing MAGE-1+ cell lines or fresh tumor.
      These data suggest that tumor-antigen-specific, MHC-restricted CTL may be grown
      from TIL in the presence of synthetic epitope peptides and expanded for adoptive
      immunotherapy in melanoma patients.

PMID- 7519126
TI  - ICAM-1 and LFA-3 enhance the ability of anti-CD3 mAb to stimulate interferon
      gamma production in interleukin-2-activated T cells.
AB  - Interleukin-2 (IL-2)-activated killer cells, also referred to as lymphokine
      activated killer (LAK) cells, are stimulated by tumor cells to express cytotoxic
      activity and to also secrete cytokines such as interferon gamma (IFN gamma) and
      tumor necrosis factor alpha (TNF alpha). We previously reported that secretion of
      cytokines by IL-2-activated T cells (LAK-T cells) is dependent on the initial
      cross-linking of the T cell receptor (TCR)-CD3-molecular complex, but the cross
      linking of accessory molecules, such as LFA-1, CD2, CD44 and CD45, on LAK-T cells
      can enhance this cytokine production. We have developed an approach involving
      interspecific gene transfer to define further the contributions of LFA-1 and CD2
      to the activation of LAK-T cells. The genes for huICAM-1 (a ligand for LFA-1) and
      huLFA-3 (a ligand for CD2) were transfected singly and in combination into a null
      mouse melanoma background, and clonal populations of cells that stably express
      ICAM-1 and/or LFA-3 were derived. Expression of the introduced ICAM-1 and/or LFA
      3 by transfected cells enhanced their ability to bind LAK-T cells; the LFA-1/ICAM
      1-mediated binding was not further enhanced by activation with phorbol 12
      myristate 13-acetate. ICAM-1- and/or LFA-3-transfected cells, in the presence of
      immobilized anti-CD3, exhibited a greater ability to stimulate IFN gamma
      secretion by LAK-T cells compared to the untransfected parental lines. This
      experimental system, which allows ICAM-1/LFA-1 and CD2/LFA-3 interactions to
      occur on the LAK-T cell at a site distal from the anti-CD3 signal, extends our
      understanding of LAK-T cell activation by establishing that both LFA-1/ICAM-1 and
      CD2/LFA-3 can mediate co-stimulation via adhesion and signaling events.

PMID- 7519128
TI  - Neutrophil integrin assay for clinical studies.

PMID- 7519127
TI  - Recognition of neuroectodermal tumors by melanoma-specific cytotoxic T
      lymphocytes: evidence for antigen sharing by tumors derived from the neural
      crest.
AB  - Melanomas from different patients have been shown to express shared tumor
      antigens, which can be recognized in the context of the appropriate MHC class I
      molecules by cytolytic T cells. To determine if T-cell-defined melanoma antigens
      are expressed on other tumors of neuroectodermal origin, four melanoma-specific
      cytotoxic T lymphocyte (CTL) cultures derived from tumor-infiltrating lymphocytes
      (TIL) were tested for lysis of a panel of 23 HLA-A2+ neuroectodermal tumor cell
      lines of various histologies, including retinoblastoma (1), neuroblastoma (8),
      neuroepithelioma (6), astrocytoma (2), neuroglioma (1), and Ewing's sarcoma (5).
      Low expression of MHC class I and/or ICAM-1 molecules was found on 22 of 23
      neuroectodermal tumor lines, and could be enhanced by treatment with interferon
      gamma (IFN gamma). Following IFN gamma treatment, three Ewing's sarcoma lines
      were lysed by at least one melanoma TIL culture, and levels of lysis were
      comparable to melanoma lysis by these TIL. Lysis could be inhibited by monoclonal
      antibodies directed against MHC class I molecules and against CD3, indicating
      specific immune recognition of tumor-associated antigens. None of the other
      neuroectodermal tumors tested were lysed by TIL, but they could be lysed by non
      MHC-restricted lymphokine-activated killer cells. This demonstration of
      immunological cross-reactivity between melanomas and Ewing's sarcomas, two tumors
      of distinct histological types with a common embryonic origin, has implications
      for the developmental nature of these CTL-defined tumor antigens. It also raises
      the possibility that specific antitumor immunotherapies, such as vaccines, may be
      reactive against more than one form of cancer.

PMID- 7519129
TI  - Induction of acidic fibroblast growth factor and full-length platelet-derived
      growth factor expression in human cardiac allografts. Analysis by PCR, in situ
      hybridization, and immunohistochemistry.
AB  - BACKGROUND: Further understanding of cardiac allograft vasculopathy (CAV) is
      needed to improve long-term survival after cardiac transplantation. The diffuse
      hyperplasia of coronary intima characteristic of CAV suggests that growth factors
      may play a role in the development of CAV. Fibroblast growth factor (FGF) and
      platelet-derived growth factor (PDGF) are potent mitogens for smooth muscle cells
      (SMCs), and PDGF is an important cofactor in the pathogenesis of native coronary
      atherosclerosis. METHODS AND RESULTS: Reverse transcriptase/polymerase chain
      reaction (RT/PCR), in situ hybridization, and immunohistochemistry were used to
      determine whether transplantation results in increased cardiac expression of
      acidic (a) FGF, basic (b) FGF, and PDGF-A and -B chains. Sixty-eight myocardial
      biopsies from 36 heart transplant recipients and 7 normal hearts were analyzed by
      PCR. aFGF mRNA was present in 54 of 61 allograft biopsies and was not found in
      any normal heart. In situ hybridization and immunohistochemistry demonstrated
      diffuse, intense expression of a FGF mRNA and protein in allograft biopsies,
      predominantly in myocytes and vascular walls. Only scattered aFGF expression was
      observed in normal hearts. mRNA for the full-length isoform of PDGF-A chain was
      found in 43 of 61 allograft biopsies and was not detected in any normal heart. In
      situ hybridization and immunohistochemistry confirmed that full-length PDGF-A
      chain mRNA and PDGF protein were present in myocytes and vascular walls.
      CONCLUSIONS: Expression of aFGF and PDGF-A chain is significantly increased in
      cardiac allografts. Cardiac myocytes and vascular walls are the predominant
      sources of aFGF and PDGF. Diffuse expression of these growth factors in cardiac
      allografts may be important in the pathogenesis of CAV.

PMID- 7519130
TI  - Correlation between cellular rejection of cardiac allografts and quantitative
      changes among T-cell subsets identified by V beta epitope expression.
AB  - BACKGROUND: Cellular rejection of an allograft is mediated in part by peripheral
      blood T cells. We tested the hypothesis that quantitative changes in T-cell
      subsets can be detected in the peripheral blood and that these changes correlate
      with rejection. METHODS AND RESULTS: T-cell subset analysis was performed by flow
      cytometry using monoclonal antibodies recognizing six isotypic epitopes of the T
      cell receptor beta-chain variable (V) region. These analyses were done at 7-day
      (mean) time intervals. Fluctuations within a given subset were determined by
      dividing the number of positive cells observed by the number of positive cells
      found on the previous analysis. For healthy volunteers observed over a period of
      30 days, 119 of 120 subset ratios (99.2%) fell between 0.5 and 2.0. For patients,
      57 of 240 subset ratios (23.8%) fell outside of this range (P < .004, chi 2). The
      occurrence of the abnormal ratios coincided more closely with cellular rejection
      (mean +/- SD, 7.7 +/- 6.2 days from a positive biopsy; median, 5 days; range, 0
      to 28 days) than did the occurrence of normal subset ratios (mean +/- SD, 14.4 +/
      10.9 days from a positive biopsy; median, 11 days; range, 0 to 44 days; P < .005
      by Mann-Whitney U test). Regression analysis confirmed a significant (P < .001, R
      = .91) temporal association between cellular rejection and abnormal subset
      fluctuations. No correlation was found between abnormal subset ratios and either
      vascular rejection or use of high-dose prednisone. CONCLUSIONS: T-cell subset
      measurement may be a method of noninvasive monitoring of cellular rejection after
      transplantation and may provide insights into the physiology of graft rejection
      with the potential for the development of more specific immunosuppressive
      therapy.

PMID- 7519131
TI  - Characterization of the early lesion of 'degenerative' valvular aortic stenosis.
      Histological and immunohistochemical studies.
AB  - BACKGROUND: Nonrheumatic stenosis of trileaflet aortic valves, often termed
      senile or calcific valvular aortic stenosis, is considered a "degenerative"
      process, but little is known about the cellular or molecular factors that mediate
      its development. METHODS AND RESULTS: To characterize the developing aortic
      valvular lesion, we performed histological and immunohistochemical studies on
      Formalin-fixed and methanol-Carnoy's-fixed paraffin-embedded aortic valve
      leaflets or on frozen sections obtained at autopsy from 27 adults (age, 46 to 82
      years) with normal leaflets (n = 6), mild macroscopic leaflet thickening (n =
      15), or clinical aortic stenosis (n = 6). Focal areas of thickening ("early
      lesions") were characterized by (1) subendothelial thickening on the aortic side
      of the leaflet, between the basement membrane (PAS-positive) and elastic lamina
      (Verhoeff-van Gieson), (2) the presence of large amounts of intracellular and
      extracellular neutral lipids (oil red O) and fine, stippled mineralization (von
      Kossa), and (3) disruption of the basement membrane overlying the lesion. Regions
      of the fibrosa adjacent to these lesions were characterized by thickening and by
      protein, lipid, and calcium accumulation. Control valves showed none of these
      abnormalities. Immunohistochemical studies were performed using monoclonal
      antibodies directed against macrophages (anti-CD68 or HAM-56), and contractile
      proteins of smooth muscle cells or myofibroblasts (anti-alpha-actin and HHF-35)
      or rabbit polyclonal antiserum against T lymphocytes (anti-CD3). In normal
      valves, scattered macrophages were present in the fibrosa and ventricularis, and
      occasional muscle actin-positive cells were detected in the proximal portion of
      the ventricularis near the leaflet base, but no T lymphocytes were found. In
      contrast, early lesions were characterized by the presence of an inflammatory
      infiltrate composed of non-foam cell and foam cell macrophages, occasional T
      cells, and rare alpha-actin-positive cells. In stenotic aortic valves, a similar
      but more advanced lesion was seen. CONCLUSIONS: The early lesion of
      "degenerative" aortic stenosis is an active inflammatory process with some
      similarities (lipid deposition, macrophage and T-cell infiltration, and basement
      membrane disruption) and some dissimilarities (presence of prominent
      mineralization and small numbers of smooth muscle cells) to atherosclerosis.

PMID- 7519132
TI  - Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after
      cardiopulmonary bypass surgery.
AB  - BACKGROUND: Patients on cardiopulmonary bypass (CPB) have an increased
      susceptibility to postoperative bleeding. Previous reports using desmopressin
      acetate (DDAVP) for the prevention of postoperative bleeding have given
      contradictory results, whereas the protease inhibitor aprotinin has been shown to
      reduce blood loss after this type of surgery. This randomized study was performed
      to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding
      after CPB. METHODS AND RESULTS: One hundred nine of 122 eligible patients were
      randomized to four different groups: Group A (n = 28) received aprotinin starting
      with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6)
      KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3
      micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of
      DDAVP, the first as in group B and an additional dose 6 hours after surgery;
      group D (n = 28) received no treatment. There was a marked reduction of
      postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in
      the aprotinin group compared with all other groups, whereas no significant effect
      was observed in either of the two DDAVP regimens. A significant reduction in the
      amount of blood used was observed only in the aprotinin group (P < .01). Of the
      plasma fibrinolytic components assayed, there was a significant reduction of the
      fibrin degradation product generation in the aprotinin group (P < .001), whereas
      a significant systemic hyperfibrinolysis was observed in both DDAVP-treated
      groups and the control group. No side effects related to the study drugs were
      observed in any patient. CONCLUSIONS: Aprotinin inhibited fibrinolysis; this
      correlated with a significant reduction of postoperative blood loss and need for
      blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial
      effect. Aprotinin offers a better alternative than DDAVP in the prevention of
      bleeding after CPB.

PMID- 7519133
TI  - Carboxyhemoglobin determined in neonatal blood with a CO-oximeter unaffected by
      fetal oxyhemoglobin.
AB  - Measurements of carboxyhemoglobin (COHb) for clinical purposes are routinely made
      with CO-oximeters. However, fetal hemoglobin (HbF) interferes with this
      spectrophotometric method. The manufacturer (Ciba Corning Diagnostics) of a new
      CO-oximeter (CCD 270) claims that COHb measurements with this instrument are
      insignificantly affected by HbF. We examined this claim through CO-oximeter
      analysis of cord blood/adult blood mixtures and compared the results with those
      obtained by gas chromatography (GC). We also studied the influence of oxygen and
      bilirubin concentrations. Measurements of COHb with CCD 270 were significantly
      lower than the GC measurements, but the differences were not clinically
      important. Linear regression analysis of HbF and COHb measurements (n = 68)
      showed significant correlation (P < 0.0001) between the two factors for the older
      CCD 2500 CO-oximeter (R2 = 0.56), but not for the CCD 270 (R2 = 0.06) or GC (R2 =
      0.02). Bilirubin concentrations, which affected COHb measurements with CCD 2500,
      did not significantly affect CCD 270 measurements. We conclude that COHb
      measurements with CCD 270 CO-oximeter are not affected by HbF or bilirubin
      concentrations.

PMID- 7519134
TI  - On the use of historical clinical data for tissue polypeptide antigen.

PMID- 7519136
TI  - Age, gender, and sensitivity to bleomycin-induced chromosome breakage in Down's
      syndrome and control populations.
AB  - The free radical theory of aging suggests that cells from individuals with
      premature aging syndromes, such as Down's syndrome, might be especially sensitive
      to radical-induced DNA damage. Although existing studies support this hypothesis,
      little work has been done on examining the impact of increasing age on radical
      sensitivity within the Down's syndrome population. Additionally, intercellular
      heterogeneity and gender differences in radical sensitivity have not been
      investigated. In this study, bleomycin-induced chromosome breakage was measured
      in lymphocytes from a population of adult men and women with Down's syndrome (age
      range 20-60 years) and a population of normal control men and women of the same
      age range. Change in breakage rates as a function of age and intercellular
      heterogeneity in breakage rates were examined in males and females of both
      groups. The findings are discussed in connection with longevity and cancer risk
      in the old male population.

PMID- 7519135
TI  - The Strecker Esophageal stent in the management of oesophageal strictures:
      technique of insertion and early clinical experience.
AB  - The Strecker Esophageal stent (Boston Scientific Corporation) offers potential
      palliation of oesophageal and oesophago-gastric obstruction by means of a self
      expanding metal stent. This stent has been used in a series of 12 patients with
      oesophageal and oesophago-gastric obstruction. Initial experience of stent
      deployment and early clinical experience is presented.

PMID- 7519137
TI  - [An analysis of HCV infection by using recombinant HCV antigen C11 and C7].
AB  - The recombinant protein C11 derived from the C region of HCV genome and C7
      derived from the nonstructural region NS3 of the HCV genome were used in ELISA to
      study 442 cases of liver diseases, including chronic hepatitis, cirrhosis and
      hepatocellular carcinoma in Beijing District. It was found that HBV infection was
      more prevalent than HCV infection in this district. Both liver cirrhosis and
      hepatocellular carcinoma were more related to the superinfection of HBV and HCV
      rather than HBV infection alone or HCV infection alone. It is suggested that
      there may be some interaction between the HBV and HCV to worsen the prognosis of
      these patients.

PMID- 7519138
TI  - [Labeling of granulocytic granules with RNase-gold probes].
AB  - By using ribonuclease-gold (RNase-G) probes, ultrastructural localization of
      ribonucleic acid (RNA) was performed in inflammatory cells from gastric mucosa
      biopsies of gastric cancer and gastritis, and in peripheral leukocytes from
      normal subjects as well as from granulocytic leukemia patients. Electron
      microscopically, the azurophilic granules of monocytes and lymphocytes in gastric
      mucosa were not labeled by RNase-G, while various cytoplasmic granules of
      neutrophils, eosinophils and basophils were all positively labeled. Labeling of
      the peripheral leukocytes from normal subjects was the same as above. It is
      important to find in the present study that the cytoplasmic granules of the
      peripheral leukemic cells from granulocytic leukemia patients were not labeled by
      RNase-G. The significance of the afore-mentioned findings lies on one hand in the
      fact that it could make a revision of the conventional views of the granular
      composition. On the other hand, the data indicate that the RNase-G technique is
      potentially explorable for future clinical utilization.

PMID- 7519139
TI  - Neurophysiological follow-up in two children with Creutzfeldt-Jakob disease after
      human growth hormone treatment.
AB  - A serial neurophysiological study has been performed of 2 children during the
      clinical course of Creutzfeldt-Jakob disease after human growth hormone (hGH)
      treatment. Evolution of the EEG pattern was typical: slow waves, periodic sharp
      wave complexes, then extinction. VEP components were moderately altered. BAERs
      performed in only 1 child were normal. The blink reflex (BR) showed an early
      alteration of the R1 component. The ERG exhibited early and profound anomalies.
      Pathological changes were obvious at the first recording, at the beginning of the
      second month after clinical onset: increase in peak latencies, morphological
      changes and important reduction of b wave amplitude (a/b amplitude ratio > or =
      0.70; normal range 0.27-0.41). The ERG was completely absent a few months later.
      These results are compared with the similar retinopathy described in CJD- or
      scrapie-infected rodents. In the 2 children, pathological changes in ERG and in
      BR were obvious several months before the development of the typical EEG pattern.
      Therefore, early ERG and BR recording can be helpful in the diagnosis of CJD,
      especially in this ataxic form following hGH treatment.

PMID- 7519141
TI  - EEG-based, neural-net predictive classification of Alzheimer's disease versus
      control subjects is augmented by non-linear EEG measures.
AB  - Attempts to classify Alzheimer's disease (AD) subjects versus controls using
      spectral-band measures of electroencephalographic (EEG) data typically achieve
      around 80% success. This study assessed the ability of adding non-linear EEG
      measures and using a neural-net classification procedure to improve this
      performance level. The non-linear EEG measures were estimated correlation
      dimension ("dimensional complexity," or DCx) and saturation (degree of leveling
      off of DCx with increasing embedding dimension). In a sample of 39 subjects (14
      ADs, 25 controls), it was found that (a) the addition of non-linear EEG measures
      improved the classification accuracy of the AD/control status of subjects, and
      (b) a back-percolation neural net predictively classified the subjects much
      better than the standard linear techniques of multivariate discriminant analysis
      or nearest-neighbor discriminant analysis.

PMID- 7519140
TI  - Discrimination between demented patients and normals based on topographic EEG
      slow wave activity: comparison between z statistics, discriminant analysis and
      artificial neural network classifiers.
AB  - The topographic distributions of absolute delta and theta powers were used to
      classify demented patients and normals by means of z statistics, discriminant
      analysis and artificial neural networks (NN). The data were taken from two
      psychopharmacological studies in mildly to moderately demented patients (111 and
      96 patients for studies I and II, respectively) and from 56 normal healthy
      controls. All patients were diagnosed according to DSM-III criteria and were free
      of medication for at least 2 weeks. The NN used was a strictly layered feed
      forward network with complete connections. The z-transformed absolute power
      values in the combined delta and theta frequency range at 17 electrodes, recorded
      in a 3 min vigilance-controlled EEG with eyes closed, were used as input. After
      having trained the NN successfully by backpropagating of errors, the
      generalization test with independent data results in a classification performance
      of 90% determined by "relative operating characteristic" analysis. The NN out
      performed z statistics and discriminant analysis. This high percentage of correct
      classifications may justify the development of further application of NNs based
      on topographic EEG data.

PMID- 7519142
TI  - Quantitative topographical EEG compared to FDG PET for classification of vascular
      and degenerative dementia.
AB  - Quantitative topographical EEG was compared with regional glucose metabolism
      measured by PET with respect to the sensitivity in the classification of mild to
      moderate dementia. In 24 patients with probable Alzheimer's disease (DAT), 19
      patients with vascular dementia (VD) and 15 age-matched healthy controls, global
      and regional EEG and PET data were analyzed. The metabolic ratio between
      typically affected and non-affected regions differentiated between DAT and VD (P
      < 0.001) as well as between DAT and normal controls (P < 0.001) even for the
      subgroup of mild dementia. In contrast to PET, global EEG changes were more
      sensitive than regional alterations for the classification into the respective
      groups. Relative theta power was most sensitive for the differentiation of
      demented patients irrespective of type of normal controls (P < 0.01), whereas
      OCC/FR alpha ratio (occipital divided by frontal power) separated between
      dementia types (P < 0.01) as well as between DAT and normals (P < 0.05).
      Additionally, EEG may help to grade severity especially in DAT. Combined use of
      EEG and PET was more discriminative and reached higher diagnostic specificity
      than each test individually. These results suggest that EEG and PET are
      complementary diagnostic procedures for the differentiation and classification of
      dementias.

PMID- 7519143
TI  - Is the appearance of mismatch negativity during stage 2 sleep related to the
      elicitation of K-complex?
AB  - There is no convincing evidence for the occurrence of mismatch negativity (MMN)
      elicited by infrequent deviant tones in a homogenous tone stream during sleep in
      adult humans. Also the data presented here failed to show an MMN during any stage
      of sleep when event-related potentials (ERPs) were averaged across all trials of
      the same sleep stage. The aim of the study was to determine whether the MMN
      appearance during sleep is related to the variations in microstates of sleep that
      differ in terms of stimulus elicited phasic EEG events. The focus was on stage 2
      sleep. The single responses to a deviant tone were classified into 3 types during
      stage 2 prior to averaging ERPs. These 3 response types included K-complex, other
      phasic EEG events and no visually discernible phasic EEG events. The results
      showed that an MMN-like deflection indeed appeared during stage 2 but only when
      the deviant tone also elicited a K-complex. This type of deflection was not seen
      when the deviant tone was presented without the intervening standard tones. This
      supports the hypothesis that a true MMN to the deviant tone was seen during stage
      2 sleep preceding a K-complex.

PMID- 7519144
TI  - Non-invasive electrical and magnetic stimulation of the brain, spinal cord and
      roots: basic principles and procedures for routine clinical application. Report
      of an IFCN committee.

PMID- 7519145
TI  - Alpha, theta and alpha-theta coma: a clinical outcome study utilizing serial
      recordings.
AB  - Alpha coma (AC), theta coma (TC) and alpha-theta coma (ATC) are transient
      clinical-electroencephalographic phenomena which do not differ from each other in
      etiology or outcome and are indicative of a severe disturbance in thalamo
      cortical physiology. Although most patients do poorly, these patterns are not
      reliably predictive of outcome, regardless of etiology. We found that AC, TC or
      ATC usually change to a more definitive pattern by 5 days from coma onset. EEG
      reactivity in subsequent patterns is relatively favorable, while a burst
      suppression pattern without reactivity is unfavorable in anoxic-ischemic
      encephalopathy.

PMID- 7519146
TI  - Functional coupling of a Ca2+/calmodulin-dependent nitric oxide synthase and a
      soluble guanylyl cyclase in vertebrate photoreceptor cells.
AB  - Electrophysiological recordings on retinal rod cells, horizontal cells and on
      bipolar cells indicate that exogenous nitric oxide (NO) has neuromodulatory
      effects in the vertebrate retina. We report here endogenous NO formation in
      mammalian photoreceptor cells. Photoreceptor NO synthase resembled the neuronal
      NOS type I from mammalian brain. NOS activity utilized the substrate L-arginine
      (Km = 4 microM) and the cofactors NADPH, FAD, FMN and tetrahydrobiopterin. The
      activity showed a complete dependence on the free calcium concentration ([Ca2+])
      and was mediated by calmodulin. NO synthase activity was sufficient to activate
      an endogenous soluble guanylyl cyclase that copurified in photoreceptor
      preparations. This functional coupling was strictly controlled by the free [Ca2+]
      (EC50 = 0.84 microM). Activation of the soluble guanylyl cyclase by endogenous NO
      was up to 100% of the maximal activation of this enzyme observed with the
      exogenous NO donor compound sodium nitroprusside. This NO/cGMP pathway was
      predominantly localized in inner and not in outer segments of photoreceptors.
      Immunocytochemically, we localized NO synthase type I mainly in the ellipsoid
      region of the inner segments and a soluble guanylyl cyclase in cell bodies of
      cone photoreceptor cells. We conclude that in photoreceptors endogenous NO is
      functionally coupled to a soluble guanylyl cyclase and suggest that it has a
      neuromodulatory role in visual transduction and in synaptic transmission in the
      outer retina.

PMID- 7519148
TI  - Neuroprotective efficacy of N omega-nitro-L-arginine after focal cerebral
      ischemia in the mouse and inhibition of cortical nitric oxide synthase.
AB  - The neuroprotective effects of various doses of N omega-nitro-L-arginine have
      been correlated with the degree of N omega-nitro-L-arginine-induced inhibition of
      cortical nitric oxide synthase activity measured ex vivo. Following focal
      cerebral ischemia induced by permanent occlusion of middle cerebral artery in the
      mouse, repeated administration of 1 mg/kg i.p. of N omega-nitro-L-arginine
      (beginning 5 min after surgery) reproducibly decreased by 66-76% the infarct
      volume measured at 6 days post-occlusion. This dose of N omega-nitro-L-arginine
      decreased cortical nitric oxide (NO) synthase activity by 70-73%. The
      neuroprotective efficacy of N omega-nitro-L-arginine increased dose-dependently
      over the range of doses of 0.1-1 mg/kg. Within this dose range of N omega-nitro-L
      arginine, there was a good parallelism between the extent of inhibition of
      cortical NO synthase activity measured ex vivo and the degree of neuroprotection.
      However, higher doses of N omega-nitro-L-arginine (3 and 10 mg/kg i.p.), which
      inhibited NO synthase activity more effectively (up to 94%) failed to
      significantly reduce the infarct size. Repeated administrations of increasing
      doses of L-arginine (up to 30 mg/kg i.p.) with a low dose of N omega-nitro-L
      arginine (1 mg/kg i.p.) caused a dose-dependent reduction in the neuroprotective
      efficacy of N omega-nitro-L-arginine while the extent of NO synthase inhibition
      measured ex vivo did not decrease significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519149
TI  - Characterisation of the porin of Rhodobacter capsulatus 37b4 in planar lipid
      bilayers.
AB  - The outer membrane of Gram-negative bacteria contains aqueous channels, porins,
      which aid the diffusion of small hydrophilic molecules across it. Escherichia
      coli, as enteric bacteria, are able to survive a hostile environment of
      proteases, surfactants, and drastic changes of osmotic pressure. Rhodobacter
      capsulatus is not an enteric bacterium and as such has not evolved to resist the
      same challenges. Porins, which have molecular weight of approximately 35 kDa,
      form trimeric channels with a solute exclusion limit of about 600 Da. Most of
      them open and close in a controlled manner as a function of p.d. This function is
      little understood at present. The functional properties of single trimers of the
      major porin of Rhodobacter capsulatus 37b4 have been investigated in planar
      artificial bilayers. On application of a suitable p.d. the observed trimer closes
      in approximately three equal steps. The behaviour is completely symmetrical as
      regards closure in response to p.d.'s of opposite polarity and is strongly cation
      selective.

PMID- 7519147
TI  - Roles of RNase E, RNase II and PNPase in the degradation of the rpsO transcripts
      of Escherichia coli: stabilizing function of RNase II and evidence for efficient
      degradation in an ams pnp rnb mutant.
AB  - The Escherichia coli rpsO gene gives rise to different mRNA species resulting
      either from termination of transcription or from processing of primary
      transcripts by RNase E and RNase III. The main degradation pathway of these
      transcripts involves a rate-limiting RNase E cleavage downstream of the
      structural gene which removes the 3' terminal stem-loop structure of the
      transcription terminator. This structure protects the message from the attack of
      3'-5' exonucleases and its removal results in very rapid degradation of the
      transcript by polynucleotide phosphorylase and RNase II. Polynucleotide
      phosphorylase is also able to degrade slowly the mRNA harboring the 3' terminal
      hairpin of the terminator. In contrast, RNase II appears to protect the rpsO mRNA
      species which retains the 3' hairpin structure. Rapid degradation of the rpsO
      mRNA is observed after inactivation of RNase II even in a strain deficient for
      RNase E and polynucleotide phosphorylase. The enzyme(s) involved in this
      degradation pathway is not known. We detected an unstable elongated rpsO mRNA
      presumably resulting from the addition of nucleotides at the 3' end of the
      transcript.

PMID- 7519150
TI  - Inhibition of cellular response to platelet-derived growth factor by low M(r)
      phosphotyrosine protein phosphatase overexpression.
AB  - The role of low M(r) phosphotyrosine protein phosphatase (PTPase) in the control
      of cell proliferation was studied. A synthetic gene coding for PTPase was
      transfected and expressed in NIH/3T3 fibroblasts. The effects of the enzyme were
      particularly evident when cells were stimulated by platelet-derived growth factor
      (PDGF). The mitogenic response to PDGF was decreased and the inhibition reached
      90%. This effect was more pronounced with respect to fetal calf serum
      stimulation. Hormone-dependent autophosphorylation of the PDGF receptor was
      significantly reduced. These results demonstrate that low M(r) PTPase, a
      cytosolic enzyme, not only affects cellular response to PDGF but also reduces the
      membrane receptor autophosphorylation.

PMID- 7519151
TI  - [Effect of small doses of pituitrin on electrocardiography of ischemia in the
      experiment].
AB  - A new type of reaction to the myocardial ischemia was established in chronic
      experiments in conscious dogs. It consists in some changes of local myocardial
      activity and, consequently, in constant or transient normalization of ECG.
      Pharmacological stabilization of this process augments myocardial resistance to
      ischemia 40-50 times and more. The role of small doses of pituitrin in this
      reaction was established.

PMID- 7519152
TI  - [Effect of antibodies specific to sarcolemma of cardiomyocytes in activity of 5
      nucleotidase in rats].
AB  - Rabbit antibodies specific to sarcolemma of cardiomyocytes have been studied for
      their effect on activity of 5'-nucleotidase ecto-enzyme of the Wistar rat
      cardiomyocytes. It is shown that incubation of isolated plasma membranes of
      cardiomyocytes of rats (100 micrograms of protein) with the gamma-globulin
      fraction of antisarcolemmal cardial serum (gamma-ASCS, 20 micrograms protein) and
      with the gamma-globulin fraction of normal rabbit serum (gamma-NRS, 0.20
      micrograms protein) promotes a decrease of the enzyme activity. An inhibiting
      effect was greatly pronounced in incubation with gamma-NRS and did not depend on
      the dose of antibodies and duration of their action. An assumption is made that
      inhibiting action of antibodies on activity of ecto-5'-nucleotidase may change
      adenosine concentration and may be one of elements in the mechanism promoting an
      increase of the intracellular calcium concentration.

PMID- 7519153
TI  - Successful resolution of persistent trophoblastic disease after partial mole with
      the EMA-CO regimen.
AB  - A 29-year-old nullipara with partial hydatidiform mole at 8 weeks had pre
      evacuation hCG levels of 275,000 mIU/ml. Free beta-hCG levels were measured as 3%
      (normal value below 4%). The patient developed persistent gestational
      trophoblastic disease, failed to respond to methotrexate and actinomycin D, but
      has responded to combination chemotherapy with EMA-CO. Such a response to EMA-CO
      was not reported previously.

PMID- 7519154
TI  - The regulation of alpha 5 beta 1 integrin expression in human muscle cells.
AB  - The expression of alpha 5 beta 1 integrin was examined in either cloned or
      fluorescence-activated cell-sorted satellite cells derived from human biceps
      muscle. Removal of serum and factors required for muscle cell growth and
      proliferation both induced terminal differentiation and resulted in a coordinate
      downregulation of mRNA transcripts encoding alpha 5 and beta 1 integrin subunits.
      A corresponding downregulation of the alpha 5 subunit occurred at the protein
      level. Treatment of cultures with 5-bromo-2'-deoxyuridine (BUdR), a thymidine
      analog which inhibits muscle cell differentiation, resulted in increased
      expression of alpha 5 integrin subunit at both the mRNA and protein levels.
      However, levels of alpha 5 subunit message and protein were still markedly
      downregulated on removal of serum and growth factors from BUdR-treated cultures,
      indicating that downregulation of alpha 5 beta 1 integrin during myogenesis does
      not require and is not a consequence of muscle cell terminal differentiation.
      Downregulation of alpha 5 integrin subunit expression could be prevented by
      maintenance of cells in medium supplemented with serum and growth factors,
      although no single defined component of this medium could on its own prevent the
      downregulation of alpha 5 integrin subunit expression. Collectively, these
      results suggest that downregulation of alpha 5 beta 1 integrin expression is not
      a consequence of muscle cell terminal differentiation, but is dependent on a
      combination of exogenous growth factors which are also required for muscle cell
      growth and proliferation.

PMID- 7519155
TI  - Heparitinase inhibition of mesoderm induction and gastrulation in Xenopus laevis
      embryos.
AB  - We have examined the involvement of proteoglycan molecules in the induction of
      mesodermal tissue in Xenopus laevis embryos. Blastocoelic injections of the
      enzyme heparitinase at early blastula stages lead to gastrulation defects and to
      failures in the development of anterior embryonic structures. The period of
      sensitivity of embryos to this treatment suggests a possible role for these
      molecules during mesoderm induction. We show that heparan sulfate proteoglycans
      (HSPGs) and chondroitin sulfate proteoglycans are the predominant sulfated
      glycoconjugates synthesized in early Xenopus embryos and that HSPGs are degraded
      by blastocoelic injections of heparitinase. Further, bFGF induction of mesoderm
      in explants of Xenopus stage 8 embryonic animal cap tissue is blocked by
      heparitinase but not by Chondroitinase ABC, using three separate criteria of
      mesoderm induction. Since HSPGs present in blastula animal cap cells are digested
      by heparitinase under the culture conditions used in the mesoderm-induction
      assay, we suggest that cell-surface heparan sulfate proteoglycans are required
      for basic fibroblast growth factor-mediated mesoderm induction.

PMID- 7519156
TI  - Experimental control of axial pattern in the chick blastoderm by local expression
      of Wnt and activin: the role of HNK-1 positive cells.
AB  - Small grafts from transfected mammalian cell lines that secrete activin or
      express Wnt-1 RNA were made to the marginal zone of entire chick blastoderms in
      culture. Grafts from appropriate control cell lines produced no effects on
      development. The activin-secreting grafts, implanted before streak formation,
      could cause the streak to form opposite their marginal position even when this
      was 180 degrees distant around the blastoderm from the original presumptive
      streak site. Alternatively, opposed twin streaks were observed, one at the
      original presumptive site and one in relation to the graft. Wnt-expressing grafts
      implanted early could also reposition axis formation, but only to graft sites
      within approximately 100 degrees of angular distance from the host's presumptive
      streak origin. No Wnt-induced twinning was observed. Grafts of both experimental
      cell types intermixed were the most effective in reorientating, twinning, or
      globally disturbing the axial pattern and led to second axes with the least
      delay, relative to normal development, in reaching headfold stages. The incidence
      and distribution of cells positive for the epitope HNK-1 was investigated during
      early stages of normal and of experimentally twinned development. Only two
      nonhypoblast regions of HNK-1 expression were consistently observed in normal
      early development; a sector in the germ wall area opaca, behind the site of
      streak formation, and then a localised region of intensely, newly expressing
      cells arising in epiblast and in anteriormost parts of the (epiblast-derived)
      streak at the half-length streak stage. Both "activin only" and "activin/Wnt"
      mixed grafts, although not control grafts, became surrounded by new sectors of
      "germ wall" HNK-1 positivity. Such positivity may therefore mark a cell group
      with a signaling role (but no anatomical participation) in streak initiation.
      However, there was no change of the local background incidence of epiblastic HNK
      1 positivity in the structure of streaks induced by "activin only" grafts. This
      indicates that most cells of the streak are specified by relatively local
      induction, rather than deriving from selective aggregation. Only grafts including
      the Wnt-expressing cells gave rise to obvious new HNK-1 expression within
      epiblast-derived cells anteriorly, as does the complete normal streak. This
      suggests that the Wnt class of response pathway can complement the activin one in
      producing rostrocaudally complete axial pattern, as has been suggested for
      amphibian development.

PMID- 7519158
TI  - Transcriptional analysis of the Escherichia coli bio operon.
AB  - Using primer extension, two in vivo transcription start points (tsp) were
      identified for rightward transcription of the Escherichia coli biotin operon, at
      nucleotides (nt) +20 and +29. The strongest leftward transcript begins at +9,
      with a tenfold less abundant transcript starting at +3. The activity of segments
      cloned into promoter probe vectors locates the major leftward promoter between nt
      +1 and +105, as expected for the +9 tsp. Although the activity of a chromosomal
      operator is reduced about 300-fold by point mutation in either arm of the
      palindrome extending from nt -20 to +20, either a half-operator segment or a full
      operator bearing the same point mutation in one arm is substantially repressed
      when cloned into pKB2000, as though cellular location strongly affects the
      operator's affinity for the repressor.

PMID- 7519157
TI  - mRNAs encoding muscarinic and substance P receptors in cultured sympathetic
      neurons are differentially regulated by LIF or CNTF.
AB  - Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) have
      previously been shown to regulate neuronal choice of neurotransmitter. In this
      present study, these factors were shown to specifically and differentially
      regulate levels of both muscarinic (subtypes m1, m2, m3, m4, and m5) and
      substance P receptor (SPR) mRNAs in sympathetic neurons of the rat superior
      cervical ganglion (SCG) using solution hybridization/RNase protection analysis.
      In vivo, neonatal rat SCG expressed predominantly m2 (10.31 +/- 0.43 pg
      mRNA/micrograms total RNA) and some m1 (1.54 +/- 0.84 pg/microgram) muscarinic
      receptor mRNA, which increased developmentally to adult levels (m2 mRNA levels
      being 60% higher than those in neonates). By contrast, m3, m4, and m5 subtype
      mRNAs were much less abundant at all time points measured. A similar
      developmental regulation was found in dissociated SCG neurons in vitro. After 16
      days in culture, m2 mRNA increased 334% to 15.76 +/- 0.68 pg/microgram, while m1
      mRNA changed little (2.03 +/- 1.00 pg/microgram). However, LIF or CNTF treatment
      (5 ng/ml, 14 days) in sister cultures completely blocked this developmental
      increase. Further, LIF treatment blocked the normal muscarinic receptor-mediated
      increase in intracellular calcium (fura-2 imaging), indicating a functional
      change in receptor phenotype. By contrast, levels of SPR mRNA, which were low in
      untreated cultures (0.037 +/- 0.025 pg SPR mRNA/microgram total RNA), were
      elevated by LIF or CNTF treatment, to 0.866 +/- 0.034 pg/microgram and 0.662 +/-
      0.148 pg/microgram, respectively. These observations indicate that muscarinic and
      SPR receptor expression are differentially regulated by the same factors in SCG
      neurons and that neuronal choice of receptor phenotype may be, at least in part,
      specifically regulated by cytokines/growth factors in the cellular milieu.

PMID- 7519159
TI  - A series of integrative plasmids for Bacillus subtilis containing unique cloning
      sites in all three open reading frames for translational lacZ fusions.
AB  - Two sets of three plasmids each were constructed based on integrative plasmids
      for Bacillus subtilis. Each set encodes resistance to either chloramphenicol or
      kanamycin. The plasmids contain a cassette consisting of the resistance gene,
      BamHI and SmaI cloning sites, and the promoterless lacZ gene. The cassette is
      flanked by the 3' and 5' ends of the amyE gene (encoding amylase) allowing
      integration of the cassette into that locus in the B. subtilis chromosome. For
      propagation and selection in Escherichia coli, the plasmids contain the pBR322
      origin of replication and the beta-lactamase-encoding gene. Within a set, each of
      the three plasmids carries the unique SmaI and BamHI restriction sites in a
      different reading frame relative to the 'lacZ gene. These sets of plasmids allow
      the easy construction of translational fusions with lacZ and single-copy
      integration at the amyE locus of B. subtilis.

PMID- 7519160
TI  - Nitro blue tetrazolium staining and hydrogen peroxide production in the rat
      retina in vitamin E deficiency and after light exposure.
AB  - Nitro blue tetrazolium (NBT) staining in normal rat retina was previously found
      to be affected by inhibition of free radical-related enzyme systems, indicating
      that NBT might be useful as a marker of free radicals. The aim of the present
      study was to investigate NBT staining in rat retina in vitamin E deficiency and
      after blue light exposure, and also to measure hydrogen peroxide (H2O2)
      production indirectly by measuring catalase activity under these conditions.
      Vitamin E deficiency resulted in morphological changes in the retina and
      increased NBT staining in the photoreceptors and in the outer plexiform layer.
      Light exposure caused increased staining in the inner segments of photoreceptors.
      The increased staining was not clearly influenced by addition of the free radical
      scavengers superoxide dismutase and catalase. The catalase activity was not
      influenced by light exposure, while it was increased in vitamin E-deficient
      retina compared to controls. The results indicate that reducing systems as
      measured by NBT were activated in the retina under these conditions. However, to
      what extent the reductants represent free radicals still has to be established
      using other methods.

PMID- 7519161
TI  - Importance of cytochrome P-450IIIA activity in determining dosage and blood
      levels of FK 506 and cyclosporine in liver transplant recipients.
AB  - We have investigated the importance of cytochrome P-450IIIA enzyme activity in
      influencing dosage of the immunosuppressive drugs FK 506 and cyclosporine after
      liver transplantation. Cytochrome P-450IIIA enzyme activity in vivo was measured
      1 yr postoperatively in 37 stable orthotopic liver graft recipients (21 receiving
      FK 506 and 16 given cyclosporine) by the erythromycin breath test and the
      production of monoethylglycinexylidide from lignocaine. A strong correlation
      existed between FK 506 dose and erythromycin breath test results (r = 0.583, p <
      0.007), but no corresponding relationship with monoethylglycinexylidide
      production was observed. The FK 506 dose (14 to 196 micrograms/kg/day) also
      correlated closely with circulating predose levels of the drug in both plasma and
      blood (r = 0.538 and 0.731, p = 0.015 and < 0.001, respectively). Although no
      correlation existed between cyclosporine dose (0.254 to 0.494 mg/kg/day) and
      trough blood levels, a relationship was demonstrated when erythromycin breath
      test results were included in the derived equation: Drug dose/cytochrome P
      450IIIA activity alpha drug level (p = 0.011 vs. 0.175 without erythromycin
      breath test). A corresponding enhancement was demonstrated with erythromycin
      breath test results to relate FK 506 dose and plasma levels (p = 0.006 versus
      0.015 without erythromycin breath test results), although breath test results and
      FK 506 levels were highly discordant (p > 0.8). The use of
      monoethylglycinexylidide test results as an alternative measure of cytochrome P
      450IIIA activity provided no comparable increase in correlation for FK 506 or
      cyclosporine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519162
TI  - Immunohistochemical phenotyping of liver macrophages in normal and diseased human
      liver.
AB  - The phenotypical heterogeneity of human liver macrophages was analyzed with
      monoclonal antibodies that recognize antigens specific for the monocyte
      macrophage lineage. Most liver macrophages in normal and diseased liver were
      positive for CD68, whereas fewer matured macrophages were detected by 25-F9.
      Comparative staining of mirror sections revealed some to be doubly positive and
      others to be singly CD68 positive. Quantitative analysis confirmed the
      difference, suggesting heterogeneity of maturation in liver macrophages. Most
      liver macrophages in the normal liver were negative for CD14, a receptor for
      lipopolysaccharide and lipopolysaccharide-binding protein complexes. Liver
      macrophages in liver diseases were activated to express CD14 at varying degrees
      and were involved in the clearance of lipopolysaccharide-lipopolysaccharide
      binding protein complexes. Fc gamma RI, a receptor for monomeric IgG that is
      involved in antibody-mediated cell cytotoxicity, was negative in the normal
      liver, but was expressed in liver macrophages at inflammatory sites (e.g., in
      piecemeal and focal necrosis) in diseased livers. Fc gamma RII was expressed in
      most liver macrophages, as well as in sinusoidal endothelial cells; Fc gamma RIII
      was expressed in a smaller number of liver macrophages. Expression of Fc gamma
      RII and Fc gamma RIII was increased in chronic active hepatitis. These results
      suggest that liver macrophages are heterogeneous in maturation and function and
      that they are activated in liver diseases as shown by the novel expression of
      CD14 and Fc gamma RI. The restricted expression of Fc gamma RI indicates that Fc
      gamma RI-positive macrophages, in cooperation with cytotoxic T lymphocytes, may
      play an important role in liver cell injury through antibody-mediated cell
      cytotoxicity.

PMID- 7519164
TI  - Florid basal cell hyperplasia of the prostate.
AB  - Florid basal cell hyperplasia of the prostate is an uncommon proliferative
      condition, most often associated with adenomatous hyperplasia. It is considered a
      benign lesion although confusion with prostatic cancer is possible when one is
      not familiar with the histopathological appearance. We report another two cases
      of the glandular type of basal cell hyperplasia with immunohistochemical
      findings. Both lesions were composed of crowded and rather small glands with
      piling up of basaloid cells. They showed immunohistochemical positivity for high
      molecular weight cytokeratin 34 beta E12, confirming their relationship with
      basal cells. We detected focal positivity of these basal cells for alpha-smooth
      muscle actin, suggesting myoepithelial differentiation. Paucity of actin-positive
      smooth muscle cells in the stroma was noticed. One of the lesions showed some
      mild cytological atypia with prominent nucleoli and increased mitotic activity.

PMID- 7519163
TI  - Involvement of annexin I and annexin II in hepatocyte proliferation: can annexins
      I and II be markers for proliferative hepatocytes?
AB  - Annexin is the name of a new family of Ca(2+)-dependent membrane-binding
      proteins. Eleven types of its related proteins have been reported to date. Among
      those, annexin I and annexin II have been reported to possess many biological
      functions in vitro. Its actual role in vivo, however, is yet unknown. The
      involvement of annexin I and annexin II in the proliferation processes of
      hepatocytes was examined in the following aspects: (a) hepatocyte proliferation
      after carbon tetrachloride-induced liver damage, (b) hepatocyte regeneration
      after partial hepatectomy and (c) postnatal development of hepatocytes. These
      results showed collectively that annexin I and annexin II were increased in
      proliferative (or regenerative) hepatocytes, suggesting that both proteins play a
      certain role in the proliferation event. Furthermore, annexin I- and annexin II
      positive hepatocytes always show a wider distribution than that of proliferating
      cell nuclear antigen or cytokeratin 7-positive hepatocytes, indicating that
      annexin I and annexin II may be useful markers for detecting not only actively
      proliferating hepatocytes but also hepatocytes in preproliferative and
      postproliferative stages.

PMID- 7519165
TI  - Keratinocyte induced chemotaxis in the pathogenesis of Paget's disease of the
      breast.
AB  - In Paget's disease of the breast, the epidermis contains large clear neoplastic
      cells. To explain the pathogenesis of this disease, the immunohistochemical
      characteristics of these cells were investigated in 25 patients. The cytoplasmic
      presence of low molecular weight cytokeratin and the absence of high molecular
      weight cytokeratin in all cases confirmed the glandular origin of the Paget
      cells. Membrane over-expression of the neu-protein was established in 96% of
      cases. It was hypothesized that epidermal keratinocytes release a chemotactic
      factor which attracts neu-over-expressing breast carcinoma cells by chemotaxis
      into the epidermis. The biological assays showed that normal keratinocytes
      release one or more chemotactic factor(s) into their conditioned medium, which
      induced spreading and motility of neu-over-expressing SK-BR-3 human breast cancer
      cells. The conditioned medium of keratinocytes also attracted the SK-BR-3 cells
      by chemotaxis in a modified Boyden chamber. Furthermore, MCF-7 human breast
      cancer cells, which do not over-express the neu-protein, were not attracted by
      chemotaxis of conditioned medium of human keratinocytes. The involvement of the
      neu-protein in spreading, motility and chemotaxis is further indicated by the
      inhibition of these processes by monoclonal antibodies against the extracellular
      domain of the neu-protein. We conclude, therefore, that the Paget cells spread
      through the epidermis due to the motility induced by a chemotactic factor, which
      is released by epidermal keratinocytes and whose influence is mediated by the neu
      protein.

PMID- 7519166
TI  - Risperidone: a novel antipsychotic medication.

PMID- 7519167
TI  - Identification of three novel mutations in the CFTR gene using temperature
      optimized non-radioactive conditions for SSCP analysis.
AB  - Optimal temperature conditions for the detection of 28 known mutations on 15
      exons of the human cystic fibrosis transmembrane conductance regulator gene by
      single strand conformation polymorphism analysis using the Diagen TGGE Apparatus
      were established. This procedure was applied to the detection of unknown
      mutations in 58 non-deltaF508 chromosomes. Three novel mutations, -471del3 (5'
      flanking region), 3171insC (exon 17a) and 4700(T)8/9 (3' non-translated region)
      of the CFTR gene were found. Mutation 3171insC occurred in conjunction with the
      delta F508 mutation on the other allele of a child presenting with severe
      pathology. Mutation -471del3 has so far only been found in one healthy individual
      and her father, and 4700(T)8/9 is a DNA sequence polymorphism.

PMID- 7519168
TI  - An MspI polymorphism in the X-specific region proximal to the pseudoautosomal
      boundary. A new example of a unique "African" marker?
AB  - A polymorphic MspI site was located in the X-specific region proximal to the
      pseudoautosomal boundary. Two alleles defined by the absence or the presence of
      the MspI site were detected by the polymerase chain reaction (PCR) in a sample of
      Bantu-speaking individuals from Cameroon. No variation for this site was observed
      in a population sample from Italy.

PMID- 7519169
TI  - Interleukin-8, interleukin-6, and soluble tumour necrosis factor receptor type I
      release from a human pulmonary epithelial cell line (A549) exposed to respiratory
      syncytial virus.
AB  - The release of interleukin-8 (IL-8), interleukin-6 (IL-6) and the soluble forms
      of the tumour necrosis factor receptor (sTNF-R) from human pulmonary type II-like
      epithelial cells (A549) after respiratory syncytial virus (RSV) infection was
      analysed. RSV infection alone induced a time- and RSV dose-dependent IL-8 and IL
      6 release from A549 cells. Furthermore, the soluble form of the TNF-RI was also
      secreted in a time- and RSV dose-dependent fashion. The soluble TNF-RII was not
      detected in the cell supernatant of infected epithelial cells. The effect of
      various cytokines [IL-1 alpha/beta, TNF-alpha/beta, IL-3, IL-6, interferon-gamma
      (IFN-gamma), transforming growth factor-beta 2 (TGF-beta 2)] and colony
      stimulating factors [granulocyte (G)-CSF; granulocyte-macrophage (GM)-CSF] on the
      IL-8 release from A549 cells was also studied. Our data show that the
      proinflammatory cytokines IL-1 alpha/beta and TNF-alpha/beta induced an IL-8
      release in non-infected A549 cells, and increased the IL-8 release of RSV
      infected A549 cells synergistically. In addition, IL-3, G-CSF, IFN-gamma and TGF
      beta 2, albeit at high concentrations, induced a low IL-8 release from non
      infected A549 cells. The enhanced IL-8 secretion rates were accompanied with
      elevated cytoplasmic IL-8 mRNA steady state levels, as was shown by Northern blot
      analysis. Cellular co-culture experiments performed with A549 cells and
      polymorphonuclear granulocytes or peripheral blood mononuclear cells revealed
      that increased IL-8 amounts were secreted in the co-culture of non-infected as
      well as RSV-infected cells. The present study suggests a central role for the
      airway epithelium during RSV infection with regard to cytokine and cytokine
      receptor release, resulting in a recruitment and activation of inflammatory and
      immune effector cells. Our data also suggest that paracrine cytokine networks and
      cell-cell contact are involved in the regulation of IL-8 secretion within the
      microenvironment of the bronchial epithelium.

PMID- 7519170
TI  - Residues within the alpha subunit sequence 304-322 of muscle acetylcholine
      receptor forming autoimmune CD4+ epitopes in BALB/c mice.
AB  - BALB/c mice develop myasthenic symptoms after immunization with rodent
      acetylcholine receptor (AChR). After immunization with Torpedo AChR (TAChR),
      their CD4+ cells become strongly sensitized against a conserved region of the
      TAChR alpha subunit sequence (residues alpha 304-322), and cross-react vigorously
      with the homologous sequences of mouse and human AChR, which are almost
      identical. Therefore AChR-specific potentially autoreactive CD4+ cells exist in
      this strain. We immunized BALB/c mice with the synthetic TAChR sequence alpha 304
      322. The CD4+ cells thus sensitized responded to TAChR, indicating that they
      recognize an epitope(s) produced upon TAChR processing. They recognized peptide
      alpha 304-322 in association with the I-Ad molecule. Anti-alpha 304-322 CD4+
      cells cross-reacted well with the corresponding murine and human synthetic
      sequences. To identify residues involved in formation of an autoimmune
      epitope(s), CD4+ cells from mice immunized with peptide alpha 304-322 were
      challenged in vitro with single residue glycine-substituted analogues of this
      sequence. Substitution of residue W311, and of any residue within the sequence
      alpha 313-319 (RKVFIDT), consistently and, in some cases, strongly affected the
      CD4+ cells response. Substitution of residues in the region alpha 311-319 had
      variable effects in different experiments, and in general affected moderately the
      CD4+ response. These results suggest that anti-alpha 304-322 CD4+ cells comprise
      several clones, recognizing overlapping epitopes which share residues alpha 311
      319. The importance of the sequence region alpha 311-319 for formation of CD4+
      cell epitope(s) was verified by testing CD4+ cells sensitized to T alpha 304-322
      with analogues of this sequence, carrying non-conservative substitutions at
      positions Q310, K314 and D318. Substitution of Q310 had minimal or no effects,
      while those of K314 or D318 strongly affected the CD4+ cell response.

PMID- 7519171
TI  - High-density lipoproteins can act as carriers of glycophosphoinositol lipid
      anchored CD59 in human plasma.
AB  - CD59 (protectin) is a glycophosphoinositol (GPI) lipid-anchored inhibitor of
      complement lysis that is expressed on the membranes of blood cells, endothelial
      cells, epithelial cells and cardiomyocytes. CD59 may be shed from cell surfaces,
      e.g. during cell injury, but when entering human plasma its fate is unknown. In
      this study we observed that radiolabelled lipid-anchored CD59, but not soluble
      urinary CD59 without anchor lipid, incorporated into high-density lipoprotein
      (HDL) particles when mixed with human serum and analysed by high resolution gel
      filtration and anti-apoA-I affinity chromatography. Only a small proportion of
      CD59 entered the low-density lipoprotein (LDL) fraction. HDL particles were
      capable of incorporating 25-42% of [125I]CD that was preinserted into the
      membranes of rabbit erythrocytes (RaE) and transferred 7-14% of [125I]CD59 back
      to RaE or to cultured human endothelial cells (EA.hy 926). Immunoaffinity
      purification and immunoblotting analysis demonstrated that HDL isolated from
      normolipidemic human serum contained small amounts of CD59. These results suggest
      that HDL particles could be involved in the recycling of GPI lipid-anchored
      molecules released from cell surfaces.

PMID- 7519172
TI  - Recombinant soluble CD59 inhibits reactive haemolysis with complement.
AB  - Three soluble forms of membrane attack complex inhibitory factor (MACIF or CD59)
      were prepared using recombinant baculovirus-infected insect cells. They consisted
      of 70, 77 and 86 amino acids, starting from the amino terminus of naturally
      occurring CD59, and were designated recombinant (r) CD59 70, 77 and 86,
      respectively. All three rCD59 lacked a glycosyl-phosphatidylinositol (GPI)
      anchor, unlike membrane CD59 which has a GPI anchor at the anchor at the carboxyl
      terminus (77th amino acid). Their activities in inhibiting complement activation
      were assayed with C5b-7 intermediate cells and C8 and C9 components. The
      inhibitory activity of rCD59 70 was as high as that of rCD59 77 and twice that of
      rCD59 86. In addition, it was one-fourth and one-hundredth lower than the
      activities of urine and erythrocyte CD59, respectively. However, when assayed in
      the presence of human serum at a final concentration of 50% (v/v), the activities
      of both urine and erythrocyte CD59 were greatly decreased to to one-tenth of that
      of rCD59 70. Purified rCD59 70 molecules were all glycosylated, but rCD59 77 and
      86 were mixtures of glycosylated and non-glycosylated molecules. The inhibitory
      activities of rCD59 77 and 86 were the same for the glycosylated and non
      glycosylated forms. These results suggest that the soluble rCD59 provide a means
      for elucidating the biological roles of CD59.

PMID- 7519173
TI  - Granulocyte and granulocyte-macrophage colony-stimulating factors exert
      differential effects on neutrophil platelet-activating factor generation and
      release.
AB  - The haemopoietic recombinant human cytokines granulocyte and granulocyte
      macrophage colony-stimulating factor (rhG-CSF and rhGM-CSF) are used to
      facilitate recovery of bone marrow function following cytotoxic chemotherapy.
      Recent clinical experience indicates that rhG-CSF is better tolerated than rhGM
      CSF. Thus, we have compared the priming effects of rhG-CSF and rhGM-CSF on
      superoxide anion (O2-) generation and platelet-activating factor (PAF) synthesis
      by neutrophils. During a 60-min incubation of neutrophils with rhGM-CSF (1 nM) or
      recombinant human tumour necrosis factor-alpha (rhTNF-alpha; 0.3 nM), cell
      associated PAF levels increased, and upon stimulation with FMLP (100 nM) there
      was a striking amplification of PAF formation (8-13-fold) and release (24-36
      fold). In contrast, in rhG-CSF (1 nM)-primed cells, there was no increase in cell
      associated PAF levels and neither PAF synthesis nor PAF release was amplified
      following stimulation with FMLP. On the other hand, each of rhG-CSF, rhGM-CSF or
      rhTNF-alpha increased subsequent FMLP (100 nM)-induced O2- generation (by 89%,
      166% and 115%, respectively). These results suggest the existence of distinct
      intracellular signalling pathways for cytokine priming. Furthermore, some of the
      more severe adverse reactions to the administration of rhGM-CSF may be a result
      of the biosynthesis and/or release of the potent inflammatory mediator, PAF.

PMID- 7519176
TI  - Ontogenetic transformation of surface epitope expression, an adaptive
      immunoevasive strategy of filarial parasites.
AB  - Filarial nematodes are highly successful in invading, persisting and propagating
      in human body and eliciting severe ailments. The exact mechanism by which,
      filarial nematodes evade the host immunity is still ill-defined. The present
      investigation on the surface antigens of S. digitata revealed the occurrence of
      shared antigens in the egg, embryo, mf and adult stages. All these stages showed
      exposed carbohydrate moieties on their surface. In situ localization studies
      proved that the egg and embryo have exposed surface epitopes whereas the
      microfilariae and adults did not have any such epitopes. Based on these
      observations, a model has been proposed on "the surface epitope hiding", as an
      immunoevasive strategy of the filarial parasite which explains why the naturally
      shed surface antigens evoke antifilarial immune response in the host even though
      the system could not recognize the microfilariae or adult parasite due to lack of
      exposed surface epitopes, permitting the parasite to escape successfully from
      immune rejection. As treatment with detergents leads to exposure of surface
      epitopes of parasites, a safe intervention of parasite surface would be an
      effective strategy for detection and ultimate control of filariasis.

PMID- 7519174
TI  - Effect of substance P on superoxide anion and IL-8 production by human PMNL.
AB  - The neuropeptide substance P (SP), a main mediator of neurogenic inflammation,
      has been shown to have direct and modulatory effects on functional responses of
      polymorphonuclear leucocytes (PMNL). In this study, we further investigated the
      effects exerted by SP on human PMNL functions. Pretreatment of PMNL with SP
      resulted in an increase of superoxide anion (O2-) production in response to
      formyl-methionyl-leucyl-phenylalanine (FMLP), concanavalin A (Con A) and
      opsonized zymosan (STZ). In contrast, the O2- production induced by tumour
      necrosis factor (TNF) was strongly inhibited by pretreatment with SP. Both
      enhancement and inhibition of O2- response were exerted by SP in a dose-dependent
      manner and at concentrations which did not directly stimulate O2- production.
      These effects were rapid in onset, and occurred after 5 min of preincubation of
      cells with the neuropeptide. At concentrations that modulated O2- production by
      PMNL, SP also directly stimulated release of the chemotactic cytokine interleukin
      8 (IL-8). Induction of IL-8 release required a longer incubation time (1 hr) with
      SP and was preceded by an increase of IL-8 mRNA steady-state levels. Furthermore,
      as well as directly stimulating IL-8 production, SP was also able to enhance the
      IL-8 release induced by other stimuli such as FMLP and TNF. The results of this
      study indicate that, in addition to the rapid and differential modulation of O2-
      production, SP also induces long-term changes such as IL-8 synthesis and release,
      and can thus amplify the process of PMNL recruitment to the inflammatory site.

PMID- 7519175
TI  - Identification of bovine T-cell epitopes for three Mycobacterium bovis antigens:
      MPB70, 19,000 MW and MPB57.
AB  - Bovine tuberculosis remains a serious problem in several regions, partly due to a
      lack of specific diagnostic tests. The aim of this study was to identify bovine T
      cell epitopes for defined Mycobacterium bovis antigens using an experimental
      model of the natural disease. Panels of synthetic peptides (16-mers with five
      residue overlaps) were produced from published amino acid sequences for MPB70,
      the 19,000 MW antigen and MPB57. In vitro lymphocyte proliferation assays were
      used to identify T-cell epitopes. Lymphocytes from experimentally infected cattle
      proliferated in response to five epitopes (residues 88-105 and 144-163 for MPB70;
      1-16 and 67-84 for the 19,000 MW antigen; and 85-100 for MBP57). These epitopes
      were not recognized by control, non-infected animals, but were recognized by
      field reactors to intradermal tuberculin testing. All five epitopes were
      recognized by three different breeds of cattle (Friesian, Charolais and
      Simmental). In addition, the bovine T-cell epitopes identified for the 19,000 MW
      antigen in this study were similar to epitopes previously reported for man and
      mouse. Thus, as well as identifying candidate reagents for improved diagnostic
      tests and vaccination, this study provides evidence for genetic promiscuity T
      cell recognition of major myobacterial epitopes.

PMID- 7519177
TI  - Alterations of brain serotonin during experimental tumor growth in mice.
AB  - Concentrations of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid
      (5-HIAA) were studied in discrete areas of brain and in large intestine of Swiss
      mice following transplantation of Sarcoma 180 (S 180) ascites tumor. Significant
      increase in 5-HT levels (2 to 3.5-fold over controls, P < 0.05) was observed in
      raphe region of the brain throughout the period of tumor growth. Concomitant
      increase, although of lesser magnitude, was recorded in raphe 5-HIAA content. 5
      HT content of hypothalamus, mid brain and caudate putamen, on the other hand,
      remained relatively unaltered except for an increase at the advanced stage of the
      disease. While mid brain and hypothalamic 5-HIAA were elevated at the late stage,
      5-HIAA values of caudate putamen were normal or slightly reduced during the
      progression of tumor. Both 5-HT and 5-HIAA levels of the large intestine showed
      an early decline followed by a modest increase at the late stages. Brain and
      plasma tryptophan levels were also elevated significantly (P < 0.05) in the tumor
      hosts. The results suggest a close relationship between increase in serotonin
      concentrations in the brain, particularly in raphe region, and the progression of
      S-180 tumor in mice.

PMID- 7519178
TI  - Inhibitory effect of morphine on granulocyte stimulation by tumor necrosis factor
      and substance P.
AB  - We demonstrate that morphine, at higher concentrations than that effective in the
      inhibition of spontaneously active cells, can antagonize stimulation of human
      granulocytes by tumor necrosis factor (TNF) or substance P. The antagonistic
      effect appears to occur indirectly by way of downregulation of the cells'
      responsiveness to these stimulatory substances. We have previously shown that
      neutral endopeptidase 24.11 (NEP) is an important enzyme in neuro- and
      autoimmunoregulation of both vertebrates and invertebrates, and that activation
      of human granulocytes by monokines and neuropeptides results in regulation of
      NEP. Exposure of intact human granulocytes to morphine increases NEP by a
      naloxone-sensitive mechanism. The increased expression of NEP downregulates the
      stimulatory effect of substance P and TNF. In the case of substance P, we
      demonstrate the significance of NEP in modulating the process of downregulation
      by use of a specific NEP inhibitor, phosphoramidon. These results indicate that
      morphine is a significant factor in downregulating immunocyte responsiveness to
      NEP substrates and also to those signal molecules (i.e. cytokines) not
      metabolized by it. In summary, we infer that opiates may be endogenous signal
      molecules, a status that appears to be amply supported by their immunosuppressive
      actions.

PMID- 7519179
TI  - Analogues of the C-terminal fragments of neurokinins with modifications at their
      C-terminal methionyl residue. Structure-activity studies.
AB  - Analogues of SP4-11 have been synthesized in which the methionyl residue is
      replaced successively by the Glu(OCH2CH3), Glu(OBzl), Hse(CH3) and Glu(CONHCH3)
      residues, and analogues of NKA4-10 and NKB4-10 have been prepared in which the
      methionyl residue is replaced by the Hse(Bzl) and Hse(CH3) residues,
      respectively. The SP4-11 analogues were tested in three in vitro preparations
      representative of NK-1, NK-2 and NK-3 receptor types. Substitution of the SCH3
      group of the Met11 side chain by the groups COOCH2CH3 and COOBzl has little
      affect on the agonist activity in NK-1 preparations, while in NK-2 the
      corresponding analogues are more potent than the parent octapeptide; that
      substituted with COOBzl being 8.2 times more potent than SP4-11. In NK-3
      preparations all analogues are weak agonists. The selectivity of all the
      analogues is reduced compared with the corresponding hexapeptide analogues. The
      SP4-11 analogues, along with those of NKA4-10 and NKB4-10, were tested for their
      binding ability in the three receptor subtypes above. The SP4-11 analogues show
      reduced affinity for NK-1 receptors, while the NKA4-10 and NKB4-10 analogues have
      almost the same affinities as NKA and NKB for NK-2 and NK-3 receptors,
      respectively. The effect of the lipophilicity of the Met11 side chain, especially
      when a phenyl group is present in the side chain, at the NK-2 receptor is
      discussed.

PMID- 7519180
TI  - Growth factor localization in choroidal neovascular membranes of age-related
      macular degeneration.
AB  - PURPOSE: Because several polypeptide growth factors are known to influence
      capillary endothelial cell mitogenesis, the authors investigated the presence of
      some of these molecules in choroidal neovascular membranes (CNVMs) removed
      surgically from human subjects with age-related macular degeneration (ARMD).
      METHODS: The authors performed immunoelectron microscopic studies on surgically
      removed submacular CNVMs from nine subjects with ARMD and from one subject with
      ARMD whose eye was studied after death. These were compared with retinal pigment
      epithelial (RPE) and choroidal tissue from eight normal subjects whose eyes were
      received after death and one received after massive trauma. RESULTS: RPE cells
      from the CNVMs were strongly immunoreactive for acidic and basic fibroblast
      growth factor (aFGF and bFGF) and for transforming growth factor beta (TGF beta).
      Some of the immunoreactivity was intracytoplasmic, but most was intralysosomal.
      In addition, some choriocapillary endothelial cells located close to the RPE
      layer in these CNVMs were immunopositive for bFGF and for FGF receptor. Reaction
      product for these two substances was located at regular intervals along the
      endothelial plasma membrane on both the anteluminal and the luminal side of the
      cells, suggesting a physiological reaction between the growth factor and its
      receptor. Choriocapillary endothelial cells deeper within the stroma were
      unreactive to bFGF and FGF receptor antibodies. There was little immunoreactivity
      for the growth factors in RPE or choriocapillary endothelial cells from normal
      eyes. The aFGF and bFGF immunoreactivity was highly specific because aFGF
      positivity was abolished when the antibody was incubated with 10(-6) M aFGF but
      not a with the same concentration of bFGF, whereas bFGF immunoreactivity was
      abolished by incubation of the antibody with bFGF but not with aFGF. RPE cells
      from normal eyes and from eyes affected by ARMD showed strong cytoplasmic
      immunoreactivity to antibodies for cytoplasmic retinaldehyde-binding protein and
      superoxide dismutase and weak reactivity to antibodies for vimentin. CONCLUSIONS:
      These results are consistent with the hypothesis that one or both FGFs are
      causally related to the development of choroidal neovascularization. The authors
      have reported similar observations in experimental choroidal neovascularization
      in pigmented rats after red krypton laser photocoagulation. TGF beta may serve to
      modulate the effects of these mitogens. The authors suggest that growth factor
      production is induced in RPE cells after physical or chemical damage. Because of
      the damage to these cells, FGF molecules can be released from the cells despite
      the absence of a "signal sequence" in the DNA coding for FGF production.

PMID- 7519181
TI  - Alpha 2-macroglobulin is present in and synthesized by the cornea.
AB  - PURPOSE: The purposes of this study were to determine whether the proteinase
      inhibitor alpha 2-macroglobulin is present in the cornea, and, if so, where it is
      located, and whether it is synthesized by the cornea, and, if so, where it is
      being synthesized. METHODS: alpha 2-Macroglobulin was immunolocalized using a
      double antibody technique and quantified by immunodot blot assays, and its
      identity was confirmed by Western blot analysis. Corneal synthesis of this
      inhibitor was determined by immunoprecipitation of extracts from corneas
      incubated in organ culture with 35S-methionine. mRNA was localized by in situ
      hybridization of 3H-labeled cDNA to the inhibitor. RESULTS: alpha 2-Macroglobulin
      was localized in the epithelial, endothelial, and stromal cells. It was also
      found in the stromal extracellular matrix. When extracts of the epithelium,
      stroma, and Descemet's membrane-endothelium were analyzed by Western blot, an
      immunoreactive band for this inhibitor was detected in all extracts. This band
      comigrated with the alpha 2-macroglobulin form isolated from plasma.
      Metabolically labeled inhibitor was immunoprecipitated from the stromal layer but
      not from the epithelial or endothelial layer. However, when examined by in situ
      hybridization, mRNA was localized to epithelial and endothelial cells in addition
      to stromal keratocytes. CONCLUSIONS: Because alpha 2-macroglobulin has the
      ability to inhibit a wide range of proteinases, it is probable that this
      inhibitor plays an important role in protecting the cornea from damage caused by
      proteinases. This includes proteinases synthesized by the cornea and those
      released from inflammatory cells and invading organisms.

PMID- 7519182
TI  - Nonadrenergic noncholinergic vasodilation in bovine ciliary artery involves CGRP
      and neurogenic nitric oxide.
AB  - PURPOSE: Characterization of the nonadrenergic noncholinergic (NANC) vasodilator
      innervation in the anterior segment in the bovine eye. METHODS: The neurogenic
      tetrodotoxin-sensitive response to electrical field stimulation (EFS) of the
      intraocular segment of the bovine long posterior ciliary artery supplying the
      ciliary body was recorded using isolated ring segments of this artery mounted on
      an isometric myograph. After adrenergic and cholinergic receptor blockade (with
      phentolamine, propranolol, and atropine), the preconstricted vessels were
      subjected to EFS by passing constant current pulses (0.3 msec, 35 mA, 0.5 to 32
      Hz) between two electrodes on either side of the vessel segments. RESULTS: EFS
      resulted in 60% relaxation of the active tone in 40 vessels. Treatment with
      capsaicin reduced the NANC response by 16 +/- 2% (P < 0.001) and inhibition of
      the NO synthase with 1 x 10(-4) M L-NOARG reduced the NANC response by 83 +/- 10%
      (P < 0.001). Desensitization of the vessels to substance P had no effect. The
      CGRP(8-37) fragment (1 x 10(-6) M) in the presence of 1 x 10(-4) M L-NOARG
      reversibly and competitively inhibited the NANC response. L-arginine partly
      antagonized the inhibition induced by L-NOARG. About 60% of the L-NOARG-sensitive
      component of the NANC response was inhibited by methylene blue. Combined
      incubation with capsaicin and L-NOARG nearly abolished the NANC response. The L
      NOARG-sensitive/capsaicin-resistant relaxation was present in endothelium denuded
      vessels. The responses to EFS were blocked by TTX. CONCLUSIONS: The neurogenic
      NANC vasodilator response in the intraocular part of the bovine long posterior
      ciliary artery supplying the ciliary body is endothelium independent and consists
      of two components: a capsaicin-sensitive component mediated by CGRP released from
      sensory nerve endings and a larger L-NOARG sensitive component mediated by a
      direct "nitroxidergic" neurotransmission. The size of the nitroxidergic NANC
      response indicates that it has a physiological relevance in vivo.

PMID- 7519183
TI  - Endotoxin-induced uveitis in the rat is attenuated by inhibition of nitric oxide
      production.
AB  - PURPOSE: These experiments were undertaken to assess the role of increased nitric
      oxide production in the pathogenesis of vascular dysfunction associated with
      endotoxin-induced uveitis. METHODS: Lipopolysaccharides (LPS) (100 micrograms of
      Salmonella minnesota) was injected into foot-pads of Lewis rats randomly assigned
      to an untreated group or to a group treated with subcutaneous injections of
      aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide
      synthase (iNOS). Controls included untreated and aminoguanidine-treated rats.
      Twenty to 24 hours later, blood flow and vascular 125I-albumin permeation were
      quantified in ocular tissues. Eyes were graded histologically for leukocyte
      infiltration into the anterior uvea and anterior chamber, and leukocyte counts
      were performed on aqueous fluid. Plasma nitrate levels were measured
      fluorometrically after enzymatic reduction to nitrite. RESULTS:
      Lipopolysaccharides markedly increased plasma nitrate levels and 125I-albumin
      permeation in aqueous fluid, retina, anterior uvea, and choroid-sclera. Blood
      flow was increased only in the anterior uvea. Aminoguanidine normalized plasma
      nitrate levels and prevented or significantly ameliorated the 125I-albumin
      permeation and blood flow changes in ocular tissues. The increased aqueous fluid
      content of lymphocytes and neutrophils in LPS-treated rats, as well as the
      increased histologic score of iritis, were significantly reduced by
      aminoguanidine. CONCLUSIONS: These results suggest that the hemodynamic and
      vascular permeability changes associated with endotoxin-induced uveitis are
      mediated in large part by increased production of nitric oxide.

PMID- 7519184
TI  - Proteoglycan components of the intervertebral disc and cartilage endplate: an
      immunolocalization study of animal and human tissues.
AB  - Monoclonal antibodies have been used to study the presence and distribution of
      various components of the proteoglycan molecule in the intervertebral disc and
      cartilage endplate. Link protein, hyaluronic acid binding region, keratan
      sulphate and chondroitin 4- and 6-sulphate have been investigated in tissues from
      humans and other mammals. Exposure of the carbohydrate and protein epitopes was
      enhanced by chondroitinase and trypsin pretreatment respectively. The degree of
      immunoreactivity varied with location, being greater in the nucleus pulposus than
      the annulus fibrosus with least reactivity in the cartilage endplate. In
      addition, there was increased staining in the pericellular domains, particularly
      in adult tissues. Areas of ectopic calcification exhibited very different
      immunoreactivity, depending on the type of calcium salt present. Calcium
      hydroxyapatite deposits showed greater staining for 8A4 (link protein), while
      calcium pyrophosphate deposits demonstrated greater staining for 3B3(-), 7D4(-)
      and 3D5 than the surrounding non-calcified matrix. Staining for chondroitin
      sulphate isomer epitopes 3B3(-) and 7D4(-), indicative of modified chondroitin
      sulphate chains, was greater in human tissues of degenerate than non-degenerate
      appearance. This suggests that expression of these epitopes may be an indicator
      of disease and subsequent reparative procedures in intervertebral disc and
      cartilage endplate, similar to that seen in articular cartilage degeneration.

PMID- 7519185
TI  - Analysis of monoclonal antibodies specific for unique and shared determinants on
      HLA-DR4 molecules.
AB  - The specificities for seven mAbs to HLA-DR4 were determined initially using
      homozygous BCLs and L-cell transfectants expressing wild-type DR molecules. Three
      antibodies (NFLD.D1, NFLD.M1, and NFLD.D7) bound all DR4 molecules, but only one
      was specific for DR4. Four antibodies (NFLD.D2, NFLD.D3, NFLD.D8, and NFLD.D10)
      reacted with some but not all DR4 subtypes and had extra reactions, particularly
      with DR gene products associated with susceptibility to RA. To localize the
      antibody-binding epitopes on DR4 molecules, the antibodies were then analyzed on
      transfectants expressing hybrid genes, which were generated by exon shuffling of
      DRB1*0403 and DRB1*0701. Two of the pan-DR4 antibodies bound epitopes that
      require the beta 2 domain while the third mapped primarily to the HVR-I region.
      One antibody NFLD.D10 to subtypes of DR4 mapped to residues 40-97 on DR beta
      1*0403 chains. Comparison of reaction patterns with amino acid sequences suggest
      that the antibodies against subtypes of DR4 are specific primarily for a region
      containing sequences postulated to determine susceptibility to RA.

PMID- 7519186
TI  - Ventilatory responses to hypoxia in rats pretreated with nonpeptide NK1 receptor
      antagonist CP-96,345.
AB  - This study reports experiments designed to evaluate the role of neurokinin-1
      (NK1) receptors for substance P (SP) in the ventilatory response to acute
      hypoxia. Ventilation was measured by indirect plethysmography in eight
      unanesthetized unrestrained adult rats before and after bolus injection of 1, 5,
      or 10 mg/kg (ip) of CP-96,345 (Pfizer), a potent nonpeptide competitive
      antagonist of the SP NK1 receptor. Ventilation was measured while the rats
      breathed air or 8% O2-92% N2 with and without administration of SP antagonist.
      Pretreatment with CP-96,345 decreased the magnitude of the hypoxic response in a
      dose-dependent fashion. Minute ventilation in rats pretreated with CP-96,345 was
      reduced by 22.1% (P < 0.05) at the highest dose (10 mg/kg), largely because of an
      attenuation of the frequency component. Although both control and treated rats
      responded to hypoxia with a decrease in duration of inspiration and expiration
      rats pretreated with CP-96,345 displayed a smaller decrease in inspiration and
      expiration than control rats (P < 0.05). We have recently shown that neuropeptide
      containing fibers are important for mediating the tachypnic response during acute
      isocapnic hypoxia in rats. The attenuation in minute ventilation at the highest
      dose (10 mg/kg) is comparable in magnitude to the attenuation observed with
      neonatal capsaicin treatment, which permanently ablates neuropeptide-containing
      unmyelinated fibers. Accordingly, this previously reported role of capsaicin
      sensitive nerves in the hypoxic ventilatory response of rats is probably
      attributable to released SP acting at NK1 receptors. One of the likely sites of
      action of SP antagonists is the carotid body.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519187
TI  - Acetylcholine and carotid body excitation during hypoxia in the cat.
AB  - The purpose of this study was to test the hypothesis that acetylcholine (ACh) is
      an excitatory neurotransmitter during the hypoxic stimulation of the carotid
      body. Cats were anesthetized, paralyzed, and artificially ventilated. The common
      carotid artery was fitted with a loop containing a stopcock for selectively
      perfusing the carotid body. Neural activity was recorded from the whole carotid
      sinus nerve. After the cats had been ventilated on 10% O2 for 3 min with the
      carotid body being normally perfused with its own hypoxic arterial blood, the
      stopcock was turned, and either equally hypoxic Krebs-Ringer bicarbonate solution
      (KRB) containing alpha-bungarotoxin, mecamylamine, and atropine or hypoxic
      blocker-free KRB perfused the carotid body for 2 min. The stopcock was returned
      to its original position, allowing blocker-free hypoxic blood to perfuse the
      carotid body once again. With this protocol we found 1) the cholinergic blockers
      reduced the carotid body response to hypoxic KRB in a dose-dependent manner; 2)
      carotid baroreceptor activity was not reduced by the blockers, suggesting that
      the action of the blockers was not nonspecific (whereas lidocaine rapidly reduced
      both chemoreceptor and baroreceptor activity); 3) inclusion of the blockers in
      perfused hypoxic blood also reduced neural output from the carotid body; and 4)
      the blockers reduced the carotid body's neural response to hypoxic KRB containing
      substance P (20 micrograms/100 ml), suggesting that substance P may be linked to
      ACh in the carotid body. We conclude that these data provide good evidence
      supportive of an excitatory role for ACh in carotid body hypoxic excitation.

PMID- 7519188
TI  - Competitive nested polymerase chain reaction for quantification of human MDR1
      gene expression.
AB  - Tumor cell resistance to cytotoxic drugs is considered one of the major obstacles
      to successful chemotherapy. Multidrug resistance (MDR) describes the simultaneous
      expression of cellular resistance to a wide range of structurally and
      functionally unrelated drugs. The development of the multidrug resistance
      phenotype is accompanied by multiple morphological and biochemical changes: (a)
      increased glutathione levels in the cytoplasm, (b) modified levels of enzymes in
      the nucleus, particularly topoisomerase II, (c) increased DNA repair capacity and
      (d) overexpression of the (human) MDR1 gene encoding a transmembrane efflux pump
      (P-glycoprotein, gp-170), which leads to decreased intracellular accumulation and
      therefore to resistance to a variety of cytotoxic drugs. In this report we
      describe a competitive polymerase chain reaction (PCR) assay for the absolute
      quantification of MDR1 mRNA. This assay uses a transcript generated in vitro as
      an internal standard which is later coamplified together with the MDR1 cDNA. Both
      cDNAs exhibit the same MDR1 primer sites but differ in the length of the
      amplicon. For a second round of amplification we applied nested MDR1 primers and
      were successful in improving the sensitivity of this competitive PCR system. This
      test for characterizing the MDR1 expression offers high sensitivity and
      specificity and is therefore of great clinical relevance. It should be useful in
      improving monitoring and design of chemotherapy.

PMID- 7519190
TI  - Insulin-like growth factor-binding protein-2 concentrations in cerebrospinal
      fluid and serum of children with malignant solid tumors or acute leukemia.
AB  - Many tumor cell lines express insulin-like growth factors (IGFs) as autocrine
      growth factors and IGF-binding protein-2 (IGFBP-2) as a major IGFBP, which, in
      turn, regulates the bioavailability and bioactivity of IGFs. The aim of our study
      was to investigate 1) whether children with malignancies have elevated IGFBP-2
      levels in cerebrospinal fluid (CSF) and serum, and 2) whether IGFBP-2 levels in
      these biological fluids could be useful markers for the diagnosis and follow-up
      of certain tumor types. We, therefore, measured IGFBP-2 levels in the CSF and
      serum of children with malignancies by Western ligand blot analysis; RIA with
      alpha IGFBP-2, a polyclonal antibody for human IGFBP-2; and immunoprecipitation
      with alpha IGFBP-2 and alpha Hec-1a, a polyclonal antibody that recognizes IGFBP
      2 and -3. Furthermore, the expression of IGFBP-2 messenger ribonucleic acid in
      tumor tissue from three central nervous system (CNS) tumor patients was analyzed
      by Northern blot analysis. We examined CSF from 21 children with malignant CNS
      tumors, 25 patients with acute leukemia, and 4 patients with peripheral solid
      tumors and compared the IGFBP-2 levels with those in CSF from 21 patients who
      received a lumbar puncture to exclude meningitis. Serum was obtained from 7
      patients with solid tumor, 12 patients with malignant CNS tumor, and 16 patients
      with acute leukemia. The serum IGFBP-2 levels were compared to serum levels in 5
      patients with sarcoma who had reached complete remission and 13 normal control
      children. CSF and serum were collected at the same time, before initiation of
      therapy. Patients with malignant CNS tumors showed elevated IGFBP-2 levels in CSF
      (P < 0.001), whereas patients with solid peripheral tumor or acute leukemia had
      normal IGFBP-2 levels in CSF. CNS tumor patients with microscopically detectable
      malignant cells in the CSF had the highest CSF IGFBP-2 levels. Serum IGFBP-2
      levels were increased in patients with solid peripheral tumors (P < 0.05),
      whereas patients in complete remission had normal serum IGFBP-2 levels. In
      summary, IGFBP-2 was elevated specifically in CSF from patients with CNS tumor,
      whereas IGFBP-2 serum levels were elevated in children with various peripheral
      tumors. We conclude that IGFBP-2 in CSF could be a specific marker for malignant
      CNS tumors. We detected high IGFBP-2 messenger ribonucleic acid expression in 1
      of 3 CNS tumor tissues analyzed.

PMID- 7519191
TI  - Effects of recombinant human growth hormone on metabolic indices, body
      composition, and bone turnover in healthy elderly women.
AB  - We conducted a controlled trial of recombinant human GH (rhGH) in 27 healthy
      elderly women (66.7 +/- 3.0 yr), of whom 8 took a stable dose of replacement
      estrogen throughout the study (plus estrogen group). Hormone or placebo was given
      as a single daily injection. A total of 19 women were assigned to receive rhGH at
      an initial daily dose of 0.043 mg/kg BW. After several weeks, 50% dose reductions
      were necessitated by side-effects. The last 7 subjects to be enrolled began
      treatment at this reduced level. A total of 13 women assigned to rhGH and 14
      women assigned to placebo completed 6 months of drug treatment. In the rhGH
      group, 6 women took estrogen; thus, the effects of rhGH were assessed separately
      by estrogen status. Circulating insulin-like growth factor-I (IGF-I) levels were
      similar at baseline (rhGH, 133 +/- 40.4 micrograms/L; placebo, 128 +/- 13). rhGH
      increased IGF-I and IGF-I-binding protein-3 (IGFBP-3) in all subjects [6 month
      IGF-I in plus estrogen women, 230 +/- 25.4 micrograms/L; in those not receiving
      estrogen (minus estrogen), 308 +/- 21.3]. No changes in IGF-I or IGFBP-3 occurred
      with placebo (IGF-I, 144 +/- 21.3 micrograms/L). Skinfold thickness measurements
      showed an 11% decrease in fat mass (P < 0.005) and a 9% decrease in percent fat
      after 6 months of rhGH treatment. No significant difference in nitrogen balance
      was seen in either group at 6 months, but rhGH increased creatinine clearance by
      9.2% (P < 0.05). rhGH dramatically increased markers of bone turnover, with more
      pronounced effects in minus estrogen women. Hydroxyproline excretion increased by
      20% and 80%, and pyridinoline excretion increased by 44% and 75% in plus and
      minus estrogen subgroups, respectively. Osteocalcin concentrations increased by
      more than 60% in minus estrogen women (P < 0.05), but did not change in the plus
      estrogen group. No changes were observed in circulating type I procollagen
      extension peptide in either group, and no change in any turnover marker was seen
      in the placebo group. rhGH did not alter blood pressure or circulating L-T4
      levels, but a transient increase in serum T3 was observed in the minus estrogen
      group at 3 months. rhGH decreased low density lipoprotein cholesterol in the
      minus estrogen group, but otherwise no significant changes in circulating
      lipoproteins or fibrinogen were observed. Eight women assigned to rhGH and 14
      placebo-treated women remained on blinded treatment through 12 months.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7519192
TI  - Somatostatin analog treatment slows growth and the tempo of reproductive
      maturation in female rhesus monkeys.
AB  - The present study tested the hypothesis that a reduction in serum GH during
      adolescence would result in slower growth and delayed puberty. Skeletal growth
      and maturation as well as indices of reproductive development were studied in
      juvenile female rhesus monkeys receiving a constant sc infusion of a somatostatin
      analog, Sandostatin, at a dose of approximately 4.50 micrograms/kg BW.day (Ssa; n
      = 6) and in untreated females (Con; n = 6) from 18 months of age through the
      luteal phase of the second ovulation. Although age at menarche was similar in Con
      and Ssa females, first ovulation was delayed significantly in Ssa females, such
      that the interval between menarche and first ovulation was significantly longer
      in Ssa females. Serum concentrations of GH, insulin-like growth factor-I (IGF-I),
      and IGF-binding protein-3 were reduced in Ssa females, particularly after
      menarche. Although changes in body weight were similar between Ssa and Con
      females, growth in height was significantly greater in Con females. Furthermore,
      peak growth velocity in height occurred at a significantly later age in SSa
      females, but at a similar degree of skeletal maturity. Serum insulin and glucose
      levels in response to iv glucose were similar in the two groups; however, fasting
      levels of serum glucose decreased significantly in both groups with advancing
      age, but the decrease was greater in Con. During the luteal phase of the first 2
      ovulatory cycles, there were diminished serum progesterone in 16.7% (2 of 12) of
      the Con and 41.7% (5 of 12) of the Ssa females. Serum estradiol was significantly
      lower throughout the first 2 ovulatory cycles in Ssa females, whereas serum LH
      and IGF-I were similar to those in Con females. Multiple regression analyses
      revealed that age at menarche was best predicted from the amount of growth in
      height before menarche, whereas those females who had higher serum IGF-binding
      protein-3 levels before menarche had an earlier growth spurt, and those who grew
      faster had a shorter interval between menarche and first ovulation. These data
      indicate that treatment with a long-acting somatostatin analog, which produces a
      relative deficiency in the GH axis, slows growth and delays the tempo of puberty.
      The data suggest that this delay may be due to a reduction in gonadal sensitivity
      to LH.

PMID- 7519189
TI  - Isolation of a neural chondroitin sulfate proteoglycan with neurite outgrowth
      promoting properties.
AB  - Proteoglycans are expressed in various tissues on cell surfaces and in the
      extracellular matrix and display substantial heterogeneity of both protein and
      carbohydrate constituents. The functions of individual proteoglycans of the
      nervous system are not well characterized, partly because specific reagents which
      would permit their isolation are missing. We report here that the monoclonal
      antibody 473HD, which binds to the surface of early differentiation stages of
      murine astrocytes and oligodendrocytes, reacts with the chondroitin
      sulfate/dermatan sulfate hybrid epitope DSD-1 expressed on a central nervous
      system chondroitin sulfate proteoglycan designated DSD-1-PG. When purified from
      detergent-free postnatal days 7 to 14 mouse brain extracts, DSD-1-PG displays an
      apparent molecular mass between 800-1,000 kD with a prominent core glycoprotein
      of 350-400 kD. Polyclonal anti-DSD-1-PG antibodies and monoclonal antibody 473HD
      react with the same molecular species as shown by immunocytochemistry and
      sequential immunoprecipitation performed on postnatal mouse cerebellar cultures,
      suggesting that the DSD-1 epitope is restricted to one proteoglycan. DSD-1-PG
      promotes neurite outgrowth of embryonic day 14 mesencephalic and embryonic day 18
      hippocampal neurons from rat, a process which can be blocked by monoclonal
      antibody 473HD and by enzymatic removal of the DSD-1-epitope. These results show
      that the hybrid glycosaminoglycan structure DSD-1 supports the morphological
      differentiation of central nervous system neurons.

PMID- 7519193
TI  - Interleukin-6 biosynthesis in human preovulatory follicles: some of its potential
      roles at ovulation.
AB  - In the present work we explored cellular sites of interleukin-6 (IL-6)
      biosynthesis in human follicular aspirates from patients undergoing in vitro
      fertilization therapy and the effects of this cytokine on oocyte fertilization
      and granulosa cell (GC) steroidogenesis. Biological IL-6 activity from 20-40
      IU/mL was present in follicular fluids from 22 patients; it was also detected in
      10 of 22 supernatants of cultured oocyte-cumulus complexes and in cumulus cell
      and GC cultures. Biological IL-6 activity in oocyte-cumulus complex cultures was
      not related to fertilization rates. Total ribonucleic acid was isolated from
      follicular aspirates and GC-enriched preparations. After reverse transcriptase
      and polymerase chain reaction cycles using oligonucleotide primers corresponding
      to known cDNA sequences for IL-6, a 126-basepair band characterized the
      amplification product of IL-6 transcripts on gel electrophoresis. To localize IL
      6 messenger ribonucleic acid, in situ hybridization analysis was performed using
      a [35S]IL-6 riboprobe. The distribution of transcripts was more dense (15% vs. 3%
      stained cells) in GC-enriched preparations, which contained more than 95% GCs,
      than in original follicular preparations, which contained 20-40% viable GCs; it
      was not significantly modified by the presence of macrophage contaminants. The
      expression of IL-6 protein was assessed by positive immunohistological stainings.
      Biological IL-6 activity was higher, and in situ hybridization signals were more
      dense and more intense in 24-h GC cultures than in 72-h GC cultures, suggesting
      that IL-6 biosynthesis was transiently induced. Under experimental conditions of
      low IL-6 endogenous levels in cultures, adding recombinant human IL-6 from 10-200
      IU/mL had no effect on progesterone production or aromatase activity in GC
      cultures free of macrophages, whereas in GC cultures including macrophage
      contaminants, stimulatory effects on basal and hCG-stimulated progesterone
      production and on basal and FSH-stimulated aromatase activities were observed.
      The present study provides strong support for the view that IL-6 is produced by
      GCs in the preovulatory follicle at the time of ovulation. In addition, we showed
      that IL-6 might be an intraovarian regulatory factor concerned with
      steroidogenesis.

PMID- 7519194
TI  - Aberrant integrin expression in the endometrium of women with endometriosis.
AB  - Integrins are ubiquitous cell adhesion molecules that undergo dynamic alterations
      during the normal menstrual cycle in the human endometrium. The alpha v beta 3
      vitronectin receptor integrin is expressed in endometrium at the time of
      implantation, but its presence is delayed in endometrium that is assessed to be
      out of phase using classical histological features. To investigate the expression
      of this integrin in women with endometriosis, we assessed the presence of the
      beta 3-subunit throughout the menstrual cycle in 268 "in-phase" endometrial
      biopsies, using immunohistochemistry. The beta 3-subunit was expressed on
      endometrial epithelium after days 19-20 of the menstrual cycle. In 241 women
      whose biopsies were obtained after day 19, a lack of beta 3 expression was found
      to be closely related to the diagnosis of endometriosis (by Wilcoxon test, P =
      0.02). This defect in integrin expression was associated with nulliparity,
      inversely related to the stage of disease, and occurred despite the presence of
      in-phase histological features. In a prospective double blind assessment of this
      integrin, we found endometrial beta 3 analysis to have a high specificity and
      positive predictive value as a nonsurgical diagnostic test for minimal and mild
      endometriosis. In conclusion, aberrant integrin expression in the native
      endometrium is associated with the finding of endometriosis and may identify some
      women with decreased cycle fecundity due to defects in uterine receptivity.

PMID- 7519195
TI  - Human fallopian tube expresses granulocyte-macrophage colony stimulating factor
      (GM-CSF) and GM-CSF alpha and beta receptors and contain immunoreactive GM-CSF
      protein.
AB  - Using specific primers, 35S-40mer oligonucleotide probe and monoclonal antibody,
      reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization,
      and immunohistochemical observations respectively revealed that human fallopian
      tube expresses granulocyte macrophage colony stimulating factor (GM-CSF) mRNA and
      protein, as well as GM-CSF alpha and beta receptors mRNA. The RT-PCR products
      revealed the predicted 286, 546 and 380 bp fragments for GM-CSF, GM-CSF alpha
      receptor and GM-CSF beta receptor respectively, which were further verified by
      restriction enzyme digestion analysis. Tubal epithelial cells in the ampullary
      and isthmus regions (ciliated and nonciliated) are the primary site of GM-CSF
      mRNA expression and its immunoreactive gene product, and present to a lesser
      extent in tubal stromal, smooth muscle, and arterial endothelial and smooth
      muscle cells. The in situ hybridization and immunostaining observations indicated
      that the expression of GM-CSF mRNA and protein appeared to be cycle dependent and
      considerably higher during mid-late proliferative and early-mid secretory, than
      early proliferative and reduced at late secretory phases of the menstrual cycle
      and postmenopausal period. The results demonstrate for the first time that human
      fallopian tube expresses GM-CSF and its alpha and beta receptors mRNA and
      contains the immunoreactive gene product for GM-CSF, and may be potentially
      regulated by ovarian steroids. The results imply the importance of GM-CSF in a
      variety of tubal functions and possibly the early embryonic development.

PMID- 7519196
TI  - Identification and cellular localization of growth hormone receptor gene
      expression in the human ovary.
AB  - While in vivo and in vitro studies in rodents, pigs and women suggest that growth
      hormone (GH) can stimulate ovarian steroidogenesis, it is not known if this
      effect is mediated by a direct action on the ovary. The absence of GH receptor
      (GHR) messenger RNA would mitigate against a direct ovarian effect. We used the
      reverse transcriptase-polymerase chain reaction and in situ hybridization to
      examine whether the GHR mRNA was present in homogenates of seven human ovaries or
      in tissue sections of ten ovaries. GHR gene expression was detected in PCR
      products after Southern blot hybridization using an oligoprobe directed to the
      intracellular domain sharing no homology to the prolactin receptor. In situ
      hybridization using the same digoxigenin-labeled oligoprobe localized the GHR
      mRNA in the granulosa cells of dominant and antral follicles, corpus luteum,
      corpora albicans and the endothelium of blood vessels. GHR mRNA was not detected
      in preantral follicles, theca interna, theca externa, oocytes, or stroma. The
      presence of GHR mRNA in human granulosa cells and corpus luteum, taken together
      with previous studies showing GH-induced stimulation of estradiol and
      progesterone secretion, suggest that GH may play a direct role in the development
      of the human follicle.

PMID- 7519198
TI  - Endothelium-dependent relaxation to substance P in human umbilical artery is
      mediated via prostanoid synthesis.
AB  - To investigate the relaxatory effect and mode of action of substance P in the
      human umbilical artery, ring segments of the artery were suspended in organ baths
      to record the circular motor activity. Substance P induced a significant
      relaxation in segments with intact endothelium pre-contracted by potassium or 5
      hydroxytryptamine. Segments devoid of their endothelium failed to relax when
      challenged with substance P. The relaxation induced by substance P was inhibited
      by the cyclo-oxygenase antagonist indomethacin, while the nitric oxide-synthetase
      inhibitor L-NG-monomethyl-arginine was without effect. These findings suggest
      that the relaxatory effect of substance P in the human umbilical artery is
      dependent on an intact endothelium. In contrast to the case in most other
      vessels, the relaxation is not mediated via the release of endothelium-derived
      relaxing factor, but seems to be dependent on prostanoid synthesis.

PMID- 7519197
TI  - Lymphoid tissue in the endometrium of women with unexplained infertility:
      morphometric and immunohistochemical aspects.
AB  - The purpose of this study was to investigate whether the endometrium of women
      with unexplained infertility differs in some immunological aspects from the
      endometrium of normal fertile women. Endometrial biopsies were obtained from 24
      normal fertile women (group I) and 24 women suffering from unexplained
      infertility (group II) at 4, 7, 10 and 13 days following the luteinizing hormone
      (LH) surge. Endometrial granulated lymphocytes were assessed morphometrically in
      2 microns resin sections. A panel of 11 monoclonal antibodies was employed to
      characterize the leukocyte subsets in frozen sections. Semi-quantification was
      performed with a Quantimet 970 image analyser. Data were analysed using one- and
      two-way analysis of variance. Compared with fertile controls, women with
      unexplained infertility had significantly lower numbers of CD8+ (T
      suppressor/cytotoxic) cells at each post-LH date. In contrast, the number of CD4+
      (T helper/inducer) cells was significantly higher in group II. Throughout the
      luteal phase, infertile women had fewer CD56+ cells than normal fertile controls.
      The volume fraction of endometrium occupied by the nuclei of endometrial
      granulated lymphocytes did not alter with the cycle stage but the mean nuclear
      diameter and axial ratio decreased from LH+7 to LH+13. The differences observed
      in endometrial leukocytic subpopulations between fertile and infertile women may
      contribute to unexplained infertility probably by affecting the embryonic
      maternal dialogue during the implantation and early placentation period.

PMID- 7519199
TI  - The effect of acute volume expansion and vasodilatation with verapamil on uterine
      and umbilical artery Doppler indices in severe preeclampsia.
AB  - Preeclampsia is associated with increased peripheral, uterine, and umbilical
      artery resistance. Acute blood pressure reduction may result in shunting of blood
      and sudden fetal distress. We therefore investigated the effects of volume
      expansion and verapamil therapy on uteroplacental and umbilical resistance during
      treatment of preeclampsia. MATERIALS AND METHODS: Five severe preeclamptics
      underwent volume expansion and subsequent vasodilatation with an infusion of
      verapamil. Invasive hemodynamic monitoring and Doppler ultrasonography were used
      to study changes in maternal, uterine, and umbilical hemodynamics. RESULTS:
      Volume expansion and subsequent verapamil therapy was associated with significant
      changes in maternal hemodynamics without significant change in uteroplacental or
      umbilical resistance. Uterine artery waveform changes were noted, with
      disappearance of notching in some cases. CONCLUSIONS: Volume expansion and
      verapamil therapy effectively reduces maternal blood pressure in preeclampsia,
      without adversely affecting uteroplacental or umbilical artery resistance.
      Uterine artery waveform changes may be associated with improved fetal outcome.

PMID- 7519200
TI  - Functional characteristics of atrophic parotid acinar cells from rats after
      liquid feeding.
AB  - Rat parotid atrophy, induced by liquid feeding over 10 days, was manifested as
      gland weight loss (40%) and histologically as acinar shrinkage. Acinar secretory
      function was investigated in the same glands using enzymatically dispersed cell
      preparations and superfused gland slices. Results were normalized for the acinar
      proportional volume, determined by stereological analysis. Although total amylase
      activity was significantly lower in liquid-fed (LD) rats, the percentage amylase
      releases elicited by isoproterenol (10 mumol/L) and carbachol (10 mumol/L) were
      unchanged from controls (CON). Superfused gland slices from LD and control (CON)
      rats exhibited increases in membrane permeability (86Rb+ efflux) and in the
      efflux and re-uptake of K+ in response to acetylcholine (10 mumol/L). However,
      the recorded maxima were significantly lower in LD than in CON (86Rb+, 27% lower;
      K+ efflux, 35% lower; K+ re-uptake, 35% lower). Similarly, after 60-minute
      equilibration, the 36Cl- content of cells from LD rats was 57% lower than that
      from CON. Carbachol (10 mumol/L), acting for 1 min with bumetanide (100 mumol/L),
      elicited an efflux of 36Cl- from cells from LD rats, but this was significantly
      lower (32.2%) in LD than in CON (49.9%). The reduced levels of ion movement are
      probably commensurate with the reduced acinar cell volume occurring in LD rats.
      These results show that mechanisms for the formation of primary saliva
      (exocytosis and transepithelial ion movements) are substantially preserved in the
      altered acinar cells of LD rats. Thus, in salivary disorders, severe
      morphological acinar atrophy may not inevitably signify exhausted secretory
      function.

PMID- 7519201
TI  - Urapidil permeates the intact blood-brain barrier.
AB  - OBJECTIVE: To determine the plasma and cerebrospinal fluid (CSF) levels of
      urapidil after i.v. administration and the effect on CSF serotonin and 5
      hydroxyindoleacetic acid (5-HIAA) concentrations. DESIGN: Open, single-dose
      study. SETTING: Post-surgery following neurosurgical removal of the hypophysis (n
      = 5) or aneurysm clipping (n = 1). PATIENTS: 6 patients, aged 32-71 years, with
      intact blood-brain barrier (BBB); 1 patient was studied twice. INTERVENTIONS:
      Single dose of 25 mg urapidil i.v. as prophylaxis of BP increase during
      extubation or as treatment of hypertensive episodes. MEASUREMENTS AND RESULTS:
      Urapidil, serotonin and 5-HIAA were measured by HPLC in CSF during 8 h after
      urapidil administration. Urapidil was detected in CSF as soon as 5 min after
      injection in 3 patients. The concentration ratio of plasma/CSF after the
      distribution phase was about 5:1. No significant effect on serotonin and 5-HIAA
      in CSF was seen. CONCLUSION: After administration of a therapeutic dose, urapidil
      permeates the BBB and may interact with central 5-HT1A-receptors.

PMID- 7519202
TI  - Weight gain and triceps skinfolds fat mass after gastrostomy placement in
      children with developmental disabilities.
AB  - OBJECTIVE: To determine appropriate outcome indicators of nutritional status that
      are measurable over time after gastrostomy placement in children with severe
      neurologic impairments. DESIGN: Twenty-two nonambulatory children met the
      selection criteria: feeding by gastrostomy of at least 50% of total energy, age
      between 1 and 12 years, diagnosis of neurologic impairments, and presurgical
      recommendation for weight gain. Each child served as his or her own control;
      three assessments were made after gastrostomy placement. SETTING: Children were
      seen in specialty outpatient clinics. STATISTICAL ANALYSES: Scores and Pearson
      product moment correlations. RESULTS: Outcomes of gastrostomy placement were (a)
      increase in actual weight, (b) increase in weight-age equivalent, (c) rate of
      weight accretion as expected by National Center for Health Statistics growth
      charts and improved z scores for half of the children, and (d) improvement in
      triceps skinfolds percentiles for nearly half (n = 10) of the children. The
      results reflect the heterogeneity of children with severe disabilities. Pearson
      correlations showed a significant relationship between chronologic age and weight
      age equivalent (r = .96), but not for weight for age and weight-age equivalent,
      or triceps skinfolds fat mass and weight-age equivalent.
      CONCLUSIONS/APPLICATIONS: Weight and triceps skinfolds fat mass were appropriate
      outcome indicators of nutritional status measurable over time. Weight-age
      equivalent and z scores were more helpful than standard growth plots for
      interpreting weight gain over time. Our data also support findings that
      undernutrition limits growth before gastrostomy placement in patients with
      disabilities. Nutritionists are encouraged to track improvement in nutritional
      status after gastrostomy placement with measurements of triceps skinfolds fat
      mass and to use the information to support families facing decisions about the
      need for this surgery.

PMID- 7519203
TI  - Early identification and treatment necessary to prevent malnutrition in children
      and adolescents with severe disabilities.
AB  - Children with severe developmental disabilities frequently have nutrition and
      growth problems that range from moderate to severe. Because of notable continuing
      medical concerns and lowered growth expectations, parents and physicians may fail
      to recognize gradual deterioration in nutritional status before severe medical
      complications occur. The two cases reported in this article illustrate the need
      for early identification and treatment to prevent the development of notable
      morbidity secondary to malnutrition. Children and adolescents who have growth
      parameters consistently below age norms require assessment and monitoring by a
      registered dietitian to detect feeding problems and intake changes and to provide
      early intervention to help prevent negative consequences (eg, dehydration,
      protein-energy malnutrition, decubitus ulcers, increased rate and duration of
      infections, and altered bowel motility). An initial assessment should consist of
      measurement of length or height, weight, triceps, and subcapsular skinfolds;
      dietary and feeding history and a review of medical history; and biochemical
      testing as indicated by the medical and dietary histories. Monitoring frequency,
      which is determined by age, severity of condition, and response to treatment, may
      vary from weekly to bimonthly.

PMID- 7519204
TI  - Function of bone marrow stromal cell lines derived from nude mice.
AB  - We previously reported that in double deficient nude.xid mice B cells failed to
      develop and their bone marrow did not produce mature B cells in vitro. However,
      when progenitors from nude.xid bone marrow were placed on a preestablished normal
      stromal cell line (AC6) they differentiated into surface IgM+ cells. This raised
      the possibility of a deficiency of nude and nude.xid stromal cells such that they
      were incapable of supporting the maturation of X-linked immune deficiency (xid) B
      cells. Here we ask whether bone marrow stromal cells from nude and nude.xid mice
      have the ability to support xid B cell lymphopoiesis. A primary stromal cell
      layer derived from nude mice supported xid B cell differentiation in vitro. We
      derived panels of stromal cell lines by transfection of primary stromal cell
      layers with a retrovirus encoding SV40 large T Ag. Several bone marrow stromal
      cell lines derived from nude and nude.xid mice supported xid B cell
      differentiation from CD43+/CD45 (B220-) to CD45 (B220+) and from CD45
      (B220+)/surface IgM- to surface IgM+. Supporting cell lines expressed both IL-7
      and insulin-like growth factor I. The frequencies of bone marrow stromal cells
      capable of supporting xid B cell differentiation were similar in normal, xid,
      nude, and nude.xid mice. These results demonstrate that nude and nude.xid mice
      have bone marrow stromal cells with normal abilities to support B cell
      maturation.

PMID- 7519205
TI  - Synergy of IL-1 and stem cell factor in radioprotection of mice is associated
      with IL-1 up-regulation of mRNA and protein expression for c-kit on bone marrow
      cells.
AB  - Administration of IL-1 and stem cell factor (SCF) to mice 18 h before lethal 60Co
      whole-body irradiation resulted in synergistic radioprotection, as evidenced by
      increased numbers of mice surviving 1,200 to 1,300 cGy doses of radiation and the
      recovery of increased numbers of c-kit+ bone marrow cells at 1 and 4 days after
      the lethal dose of 950 cGy. Anti-SCF Ab inhibited IL-1-induced radioprotection,
      indicating that endogenous production of SCF is necessary for radioprotection by
      IL-1. Conversely, radioprotection induced by SCF was reduced by anti-IL-1R Ab,
      indicating that endogenous IL-1 contributes to SCF radioprotection. SCF, unlike
      IL-1 does not induce hemopoietic CSFs and IL-6 or gene expression of a scavenging
      mitochondrial enzyme manganese superoxide dismutase in the bone marrow,
      suggesting that SCF and IL-1 radioprotect by distinct pathways. The mRNA
      expression for c-kit (by Northern blot analysis) and 125I-SCF binding on bone
      marrow cells was elevated within 2 and 4 h of IL-1 administration respectively.
      Four days after LD 100/30 radiation the recovery of c-kit+ bone marrow cells was
      increased sixfold in IL-1-treated mice, almost 20-fold in SCF-treated mice, and
      40-fold in mice treated with the combination of the two cytokines. Thus,
      endogenous production of both IL-1 and SCF is required for resistance to lethal
      irradiation and the synergistic radioprotective effect of the two cytokines may,
      in part, depend on IL-1 and SCF-induced increases in numbers of c-kit+
      hemopoietic stem and progenitors cells that survive lethal irradiation.

PMID- 7519206
TI  - Developmental regulation of the TCR zeta-chain. Differential expression and
      tyrosine phosphorylation of the TCR zeta-chain in resting immature and mature T
      lymphocytes.
AB  - The zeta subunit of the TCR complex targets receptor surface expression, is
      phosphorylated on tyrosine residues upon T cell activation, and is implicated in
      signal transduction after TCR ligation. Here we show that, although intrathymic
      expression of the murine TCR-associated zeta-chain relative to the other chains
      of the Ag receptor complex remains unchanged during early thymocyte development,
      there is a doubling of TCR-associated zeta-chain surface expression upon
      thymocyte maturation. The ratio of tyrosine-phosphorylated relative to
      nonphosphorylated TCR-associated zeta-chain also changes with thymocyte
      development. This ratio was quantified after the purification and detergent
      extraction of receptor complexes from freshly isolated immature or mature
      thymocytes. Immunoprecipitation of the zeta-chain released from the complex
      allowed for the isolation of the tyrosine-phosphorylated and nonphosphorylated
      forms of TCR-associated zeta-chain. Intracellular free zeta-chain was
      characterized by immunoprecipitation after clearing the cell lysate of intact TCR
      complexes. Densitometric analysis of immunoblots indicated that surface
      phosphorylated zeta-chain is more abundant in immature relative to mature T cell
      populations, whereas the inverse is true of intracellular phosphorylated zeta
      chain. Surface phosphorylated zeta-chain also migrated at a higher m.w. than its
      cytoplasmic counterpart, suggesting that it is more highly modified on some or
      all of its available tyrosines. These findings demonstrate that the stoichiometry
      and post-translational modification of the TCR complex are regulated, in vivo,
      and may determine the functional maturation of T cell signaling, selection, and
      activation.

PMID- 7519207
TI  - Antigen-specific early primary humoral responses modulate immunodominance of B
      cell epitopes.
AB  - Accumulation of primary Abs against two distinct epitopes on a designed
      polypeptide, MEP-1, was examined. The early primary response was predominantly
      against a C-terminal epitope (MEP 77-100), although subsequent maturation
      established an epitope within the N-terminal half (MEP 17-31) as the
      immunodominant one. Inversion of immunodominance correlated with the inability of
      anti-MEP 77-100 B cells to interact productively with T cells, which consequently
      received reduced help. Interaction between epitope-specific B and T cells was
      found to be attenuated in the presence of early primary anti-MEP-1 antiserum, and
      the extent of inhibition was directly proportional to the level and affinity of
      epitope-specific Igs. Therefore, it seems that early primary Abs to a
      multideterminant Ag selectively down-regulate maturation of epitope-specific
      primary humoral responses.

PMID- 7519208
TI  - Ligand motifs of HLA-DRB5*0101 and DRB1*1501 molecules delineated from self
      peptides.
AB  - Antigenic peptides are presented to CD4+ T cells by MHC class II molecules via a
      highly polymorphic peptide-binding groove. The two HLA-DR alleles isotypically
      expressed on HLA-DR15Dw2-positive cells, DRB1*1501 (DR2b) and DRB5*0101 (DR2a)
      molecules, show a number of differences in polymorphic residues of the beta
      chain, including the Gly-Val-dimorphism at position beta 86. Therefore, different
      requirements for interaction of peptides with these alleles must be expected. In
      this study, naturally processed self-peptides were eluted from purified HLA
      DR15Dw2 molecules and related to DRB1*1501 or DRB5*0101 molecules by binding
      assays. An alignment of self-peptides and foreign peptides allowed the
      delineation of putative anchor motifs. N- and C-terminally truncated and alanine
      substituted derivatives of the DR15Dw2 restricted myelin basic protein epitope
      MBP(85-105) confirmed their validity. Thus, DRB5*0101 requires a bulky
      hydrophobic residue (F or Y) at position i as a primary anchor, and Q or an
      aliphatic residue, such as V, I, or M, at position i + 3; positively charged
      residues at positions i + 7 and i + 8 are secondary anchors. For DRB1*1501, a
      nonaromatic, hydrophobic anchor (L, V, or I) at position i is supplemented by a
      bulky hydrophobic residue (F or Y) at position i + 3 as primary anchor; an
      additional hydrophobic side chain represented by M, I, V, or F occurs at position
      i + 6. Therefore, MBP(85-105) seems to contain two MHC interaction sites for
      DRB1*1501 and DRB5*0101, respectively, that may contribute to its
      immunodominance. Because HLA-DR15 Dw2 is associated with susceptibility to
      develop multiple sclerosis, the delineation of ligand motifs of the two DR2
      alleles may help to study the interaction between potential autoantigenic
      peptides and these molecules in the future.

PMID- 7519209
TI  - A novel population of expanded human CD3+CD56+ cells derived from T cells with
      potent in vivo antitumor activity in mice with severe combined immunodeficiency.
AB  - Recently, we have reported a novel protocol for the generation of highly
      efficient cytotoxic effector cells by culturing PBLs in the presence of IFN
      gamma, IL-2, mAb against CD3, and IL-1 alpha. We have termed these cultures
      cytokine-induced killer (CIK) cells because the phenotype of the cells with the
      greatest cytotoxicity expresses both the T cell marker CD3 and the NK cell marker
      CD56. Cells with this phenotype are rare (approximately 1 to approximately 5%) in
      uncultured PBLs. CD3+CD56+ cells expand nearly 1000-fold under these culture
      conditions. The majority of the CD3+CD56+ cytotoxic cells in CIK cultures were
      derived from CD3+CD56- T cells, and not CD3-CD56+ NK cells. Expression of CD56,
      but not CD8, on CD3+ cells correlated with the greatest cytotoxicity against
      various cellular targets. We have used mice with severe combined immunodeficiency
      (SCID) injected with human lymphoma cells to evaluate the in vivo antitumor
      effects of CIK vs lymphokine-activated killer (LAK) cells. Groups of animals
      inoculated with 1 x 10(6) SU-DHL4 cells (a human B lymphoma cell line with a
      t(14;18) chromosomal translocation), injected 1 day later with CIK cells either
      i.v. or i.p., had significantly prolonged survival compared with control animals
      injected with tumor cells alone (median survival 90 days vs 58 days, p < 0.001)
      or animals treated with LAK cells (median survival 90 days vs 68 days, p <
      0.002). Approximately 30% of the SCID mice challenged with SU-DHL4 cells and
      treated with CIK cells became long-term survivors compared with none of the
      animals treated with LAK cells. No molecular evidence of occult lymphoma was
      found in the CIK cell-treated long-term survivors when their bone marrow, spleen,
      liver, and lung were analyzed by t(14;18) PCR at the end of 6 mo. By using these
      culture conditions, a novel population of cytotoxic cells can be generated
      readily from T cells that have superior in vivo antitumor activity in SCID mice,
      as compared with LAK cells.

PMID- 7519210
TI  - B lymphocytes of mice display an aberrant activation phenotype and are cell cycle
      arrested in G0/G1A during acute infection with Trypanosoma brucei.
AB  - Humans and domestic animals with African trypanosomiasis exhibit abnormalities of
      immune function characterized by polyclonal lymphocyte activation and,
      paradoxically, progressive immunodeficiency. Mice infected with Trypanosoma
      brucei clone IaTat1.2 develop a fulminant parasitemia by day 5 of infection. B
      lymphocytes isolated from spleens of infected mice display an aberrant activation
      phenotype manifested by decreased CD23 and surface IgM, increased CD69 and L
      selectin, and normal levels of surface IgD, MHC class II, CD32, and transferrin
      receptor. Kinetic analyses showed that CD23 and surface IgM were continuously
      down-regulated from day 2 through day 5, whereas MHC class II was elevated on
      days 2 and 3, but returned to normal levels by day 5, suggesting that CD23 and
      MHC class II are independently regulated in T. brucei infection. The aberrant
      activation phenotype of B cells responding in vivo to T. brucei was accompanied
      by impaired responsiveness of these B cells to mitogenic stimulation in vitro.
      The pathologic phenotypic and functional properties of B lymphocytes from T.
      brucei-infected mice can be partially accounted for by the virtual total arrest
      of B cells in G0/G1A of the cell cycle. The B lymphocyte alterations observed in
      the present studies provide new insight into the immunopathology of African
      trypanosomiasis. We propose that terminal infection with T. brucei induces early
      activation events in host B lymphocytes, but that the activation response becomes
      aberrant by the development of what seems to be a total block in cell cycle
      progression.

PMID- 7519211
TI  - Identification of two novel regions of human IL-6 responsible for receptor
      binding and signal transduction.
AB  - The pleiotropic cytokine IL-6 has been predicted to be a protein with four
      antiparallel alpha-helices. Human IL-6 acts on human and murine cells, whereas
      murine IL-6 is only active on murine cells. The construction of a set of chimeric
      human/murine IL-6 proteins has recently allowed us to define a new region
      (residues Lys41-Glu95) within the IL-6 molecule as being important for receptor
      binding and biologic activity. We subdivided and analyzed this region, which
      primarily corresponds to the loop between the first and second alpha-helix of IL
      6 with respect to its role in the interaction with the ligand binding subunit of
      the IL-6 receptor complex and with the IL-6 signal-transducing protein gp130. By
      construction and analysis of human/murine chimeric IL-6 molecules with only 7 to
      10 amino acid residues different from human IL-6 we show that two distinct parts
      of this region are responsible for receptor binding and signal transduction. On
      the basis of the recently published structure of granulocyte-CSF, we present a
      three-dimensional model for the tertiary structure of IL-6, which, together with
      the IL-6 receptor interaction data, allows for the rational design of human IL-6
      receptor antagonists.

PMID- 7519212
TI  - Human T lymphocyte chemotaxis and adhesion induced by vasoactive intestinal
      peptide.
AB  - Vasoactive intestinal peptide (VIP), a 28-amino acid peptide of the glucagon
      secretin family, has been reported to have significant immunoregulatory
      properties. In the present study, we demonstrate that VIP has potent chemotactic
      effects on T lymphocytes. At concentrations of between 10(-8) and 10(-9) M, VIP
      stimulated significant in vitro chemotaxis of T lymphocytes from both CD4+ and
      CD8+ subsets. VIP produced more potent chemotactic effects on unstimulated T
      cells than on anti-CD3-activated cells. Following anti-CD3 activation, binding of
      125I-labeled VIP to T cells was reduced and this correlated with a reduction in
      receptor number without any change in affinity. Preincubation of unstimulated T
      cells with VIP produced increases in adhesion to ICAM and VCAM integrins. In
      addition, VIP pretreatment significantly increased unstimulated T cell adhesion
      to the extracellular matrix protein fibronectin. However, VIP induced less
      binding of activated T cells to fibronectin. Taken together these results suggest
      that VIP is a potent chemoattractant and stimulant of adhesion for T lymphocytes.
      In contrast to chemokines that are more active on stimulated T cells, such as
      RANTES, this neuropeptide preferentially targets unactivated T cells, suggesting
      that it may play a greater role in homing and distribution of lymphocytes.

PMID- 7519213
TI  - IgE-dependent IL-4 secretion by human basophils. The relationship between
      cytokine production and histamine release in mixed leukocyte cultures.
AB  - IL-4 protein and mRNA have recently been detected in pure basophil cultures after
      stimulation. It has also been established in mixed leukocyte cultures obtained by
      elutriation and challenged with anti-IgE that the basophil is the only cell that
      makes detectable IL-4. We have used cells prepared using Percoll gradients (5 to
      30% basophils) to study the relationship between histamine release and IL-4
      synthesis. In cultures challenged with anti-IgE after a 15-min pretreatment with
      IL-3, detectable IL-4 secretion ranged from 40 to 630 pg/10(6) basophils in 18 of
      22 donors, with no significant correlation (r = 0.21, p = 0.34) with basophil
      purity. IL-4 synthesis was dissociated from histamine release, with optimal
      production consistently occurring at 10 ng/ml anti-IgE, whereas histamine levels
      peaked at 50 to 100 ng/ml of stimulus. Stimulation with anti-IgE alone was
      sufficient for IL-4 secretion but protein levels were enhanced two- to threefold
      in low responders by increasing the calcium concentration to 5 mM with no
      significant changes in histamine release. The IgE-independent secretagogues, F
      met peptide (1 microM) and C5a (25 ng/ml), demonstrated limited ability to
      generate detectable IL-4, despite promoting vigorous histamine release.
      Additional studies showed no significant difference between IL-4 secretion in
      atopic and nonatopic donors. Finally, IL-4 levels generated with specific Ags
      were comparable to those levels produced in response to anti-IgE. We predict that
      basophil IL-4 generation will have a proinflammatory effect, but it appears that
      the signal transduction mechanisms for its synthesis and release differ from
      those for histamine release and thus may require different methods of
      pharmacologic control.

PMID- 7519215
TI  - Human polymorphonuclear leukocytes lack detectable nitric oxide synthase
      activity.
AB  - Nitric oxide regulates polymorphonuclear leukocyte (PMN) function, but whether or
      not human PMNs express nitric oxide synthase (NOS) activity is controversial. We
      studied NOS activity in human PMNs by using human aortic endothelial cells
      (HAECs) for comparison. The conversion of L-arginine to L-citrulline, a
      relatively specific measure of NOS activity, was easily measured and inducible in
      fractionated HAECs, and > 90% of all L-arginine conversion was blocked by the NOS
      inhibitor, N omega-amino-L-arginine (L-NAA). In fractionated PMNs, L-arginine
      conversion was low and was unaffected by L-NAA. In addition, NOS activity was not
      induced in PMNs by LPS, IL-1 beta, or IFN-gamma. In a whole-cell assay, total L
      arginine conversion was much lower in human PMNs compared with HAECs (3.38 +/-
      0.21 vs 157.5 +/- 10.28 pmol/h/10(6) cells, respectively; p < 0.01). This
      conversion in whole PMNs was not increased in vitro by LPS, IFN-gamma, IL-1 beta,
      or TNF-alpha nor decreased by W13, a calmodulin inhibitor. Furthermore, PMNs
      isolated from four volunteers before and after challenge with i.v. LPS (4 ng/kg)
      showed no increase in L-arginine to L-citrulline conversion. Nitrite and nitrate
      release from human PMNs was 35-fold lower than for HAECs and was not inhibited by
      L-NAA. These data suggest that human PMNs do not express NOS activity.

PMID- 7519214
TI  - Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide
      induced TNF-alpha and IL-1 beta production by human monocytes.
AB  - Bacterial LPS stimulates human monocytes to secrete inflammatory cytokines, which
      are involved in several disease processes. However, the mechanism of LPS
      activation of cytokine expression and secretion is not completely understood. In
      this study, we investigated the signal transduction pathways involved in LPS
      stimulated TNF-alpha and IL-1 beta secretion. TNF-alpha and IL-1 beta secretion
      were completely blocked by protein kinase C (PKC) and cyclic nucleotide-dependent
      protein kinase inhibitor, H-7, but were not affected by H-89, a specific cyclic
      nucleotide-dependent protein kinase inhibitor. In addition, LPS was found to
      induce activation of PKC, reaching maximal activity at 30 min and returning to
      unstimulated levels after 60 min. LPS stimulation only slightly increased
      intracellular levels of diacylglycerol, the natural activator of PKC, and
      pretreatment of monocytes with the diacylglycerol-kinase inhibitor, R59022, did
      not affect LPS-stimulated TNF-alpha secretion. LPS-induced PKC activation was
      found not to be affected by blocking of the LPS receptor, CD14, with mAb or by
      inhibition of protein tyrosine kinase with herbimycin A. However, these agents
      suppressed LPS-induced TNF-alpha secretion and TNF-alpha mRNA accumulation. The
      results suggest that TNF-alpha and IL-1 beta secretion after LPS stimulation of
      human monocytes requires the activation of protein tyrosine kinase and PKC,
      upstream to the activation of gene transcription. The activation of PKC by LPS is
      probably mediated by a diacylglycerol-independent pathway.

PMID- 7519216
TI  - FK506 inhibits graft-versus-host disease and bone marrow graft rejection in
      murine recipients of MHC disparate donor grafts by interfering with mature
      peripheral T cell expansion post-transplantation.
AB  - FK506 was evaluated as the sole graft-vs-host disease (GVHD) preventive agent in
      murine recipients of fully allogeneic donor grafts. FK506 (36 mg/kg given as a
      suspension on days 0 through 13, then three times per wk through day 29 post-bone
      marrow transplantation (BMT)) reproducibly led to 50 to 90% of FK506-treated
      recipients surviving a 60- to 103-day observation period. High doses of
      cyclosporin A did not protect mice from lethal GVHD. A kinetic study performed in
      mice that received FK506 demonstrated that mature donor CD3+, CD4+, and CD8+ T
      cells in the spleen were each reduced by > or = 64%, as compared with vehicle
      treated control mice, although this effect was short lived. Thymic reconstitution
      studies revealed a remarkable decrease in mature CD4+ cells and cells expressing
      the activation Ag, CD69. In contrast, less mature CD4+8+ thymocytes were not
      reduced significantly and total thymocyte numbers were only marginally decreased.
      The fact that peripheral reconstitution of CD4+8- or CD8+4- T cells was impaired
      significantly at this time indicated that FK506 had a major effect on thymic
      maturation and/or thymic emigration. In two models specifically designed to study
      alloengraftment, recipients of pan-T cell-depleted (TCD) donor marrow and FK506
      were noted to have accelerated hemopoietic recovery and augmented long-term
      multilineage peripheral blood alloengraftment, in marked contrast to controls (86
      to 97% mean donor cells vs 0% in controls for all lineages). These data
      demonstrate that FK506 prevents GVHD and graft rejection in vivo by inhibiting
      mature T cell expansion post-BMT.

PMID- 7519217
TI  - Identification and characterization of IL-2 hyper-responsive NZB/WF1 CD5- B
      cells.
AB  - The responsiveness of CD5- and CD5+ B cells of BALB/c and NZB/WF1 mice to various
      cytokines was examined with respect to their growth and differentiation. BALB/c
      splenic CD5- B cells required longer incubation with IL-2 or pretreatment with IL
      4 to respond to IL-2 by DNA synthesis, whereas NZB/WF1 CD5- B cells were highly
      competent to IL-2. Flow cytometric analysis demonstrated that NZB/WF1 and BALB/c
      CD5- B cells had higher and intermediate proportions of B cells positive for IL
      2R beta, respectively. On the other hand, BALB/c and NZB/WF1 splenic CD5+ B cells
      consisted of lower proportion of B cells positive for IL-2R beta than did their
      corresponding CD5- B cells and grew meagerly in response to IL-2. Peritoneal
      exudative CD5+ B cells of NZB/WF1 mice lacked IL-2R beta mRNA expression and
      failed to respond to IL-2. Although both BALB/c and NZB/WF1 CD5- B cells
      pretreated with anti-IgM, IL-4, and IL-5 responded to IL-2 by DNA synthesis, only
      BALB/c CD5- B cells developed into IgM-producing cells. Furthermore, BALB/c, but
      not NZB/WF1 CD5-, B cells pretreated with anti-IgM and IL-5 responded to IL-2 by
      IgM production without DNA synthesis. Thus, cross-talk between IL-4 and IL-2
      operated in the growth responses of both BALB/c and NZB/WF1 splenic CD5- B cells,
      whereas cross-talk between IL-5 and IL-2 operated only in the differentiation of
      BALB/c CD5- B cells, providing us with another intriguing functional abnormality
      of NZB/WF1 B cells.

PMID- 7519218
TI  - Targeted lymph node immunization with simian immunodeficiency virus p27 antigen
      to elicit genital, rectal, and urinary immune responses in nonhuman primates.
AB  - A s.c. route of immunization was developed in non-human primates, which targets
      the genitourinary-rectal associated lymphoid tissue. A vaccine consisting of rSIV
      gag p27, expressed as hybrid Ty virus-like particles (p27: Ty-VLP) was
      administered in the proximity of the internal iliac lymph nodes. Secretory IgA
      and IgG Abs to the p27 Ag were elicited in the vaginal, male urethral, rectal and
      seminal fluids, urine and serum. Two or more immunodominant B cell epitopes were
      identified within peptides 51-90 and 121-170 of the sequence of p27, using serum
      or biliary IgA and IgG Abs. CD4+ T cell proliferative responses to p27 were
      elicited predominantly in the targeted internal iliac, as well as the inferior
      mesenteric lymph nodes and the spleen, but not in the unrelated lymph nodes.
      These cells were then studied for helper function in p27 specific B cell Ab
      synthesis. Specific IgA and IgG Abs were detected in the same lymphoid tissues as
      those that displayed proliferative responses. However, cross-over reconstitution
      experiments between splenic and iliac lymph node B and CD4+ T cells suggest that
      the iliac B cells are essential for specific IgA Ab synthesis, whereas splenic B
      cells preferentially synthesize IgG Ab. The targeted lymph node (TLN) route of
      immunization gave comparable B cell, proliferative T cell, and Th cell responses
      to the vaginal, male genitourinary, and rectal mucosal routes, which were
      augmented by oral immunization. However, the TLN route induced urinary and
      seminal fluid sIgA and IgG Abs in addition to genital and rectal Abs. Generating
      secretory IgA and IgG Abs at the mucosal surfaces, and T and B cell immunity in
      the regional draining lymph nodes, spleen and circulation by TLN immunization may
      prevent transmission of virus through the mucosa, dissemination of the virus, and
      the formation of a latent reservoir of infection.

PMID- 7519219
TI  - Treatment with dextran-conjugated anti-IgD delays the development of autoimmunity
      in MRL-lpr/lpr mice.
AB  - The onset of clinical disease in autoimmune MRL-lpr/lpr mice is preceded by a
      switch from predominantly IgM production to IgG production. Previous studies have
      shown that IgG autoantibodies play a central role in the development of life
      threatening glomerulonephritis in this strain. Delaying or preventing the switch
      from IgM to IgG production might therefore be of therapeutic benefit. We
      previously documented similarities in the B cell repertoire expressed by young
      MRL-lpr/lpr mice and normal mice treated with the polyclonal activator LPS.
      Recent in vivo studies indicate that cross-linking membrane IgM or IgD can
      suppress LPS-dependent IgG production in normal animals. These observations led
      us to examine whether membrane cross-linking could also lower serum IgG levels in
      MRL-lpr/lpr mice. Lupus-prone animals were treated with multivalent anti-IgD
      conjugated to high m.w. dextran. This anti-IgD dextran conjugate was previously
      shown to reduce IgG production in LPS-stimulated normal animals. Treatment of
      young lupus-prone MRL-lpr/lpr mice resulted in a significant reduction in the
      total number of B cells secreting IgG and lower serum titers of IgG anti-DNA and
      IgG anti-histone autoantibodies. Anti-IgD dextran treatment also delayed the
      development of glomerulonephritis and improved survival. Thus, anti-IgD dextran
      interfered with autoantibody-dependent disease progression, perhaps by inhibiting
      the switch from IgM to IgG autoantibody production.

PMID- 7519220
TI  - The majority of neutralizing Abs in HIV-1-infected patients recognize linear V3
      loop sequences. Studies using HIV-1MN multiple antigenic peptides.
AB  - Multiple antigenic peptides (MAP) comprising eight synthetic peptides
      corresponding to the V3 loop of HIV-1MN or HIV-1IIIB linked to a lysine core were
      used to characterize the humoral Ab response of HIV-1-infected patients against
      this domain. One hundred percent of the tested sera from HIV-1-infected European
      patients reacted significantly with the HIV-1MN V3 loop MAP. Most, but not all,
      sera also reacted against the HIV-1IIIB V3 loop MAP, albeit with low titers. The
      in vitro neutralization capacity of the patients' sera against HIV-1MN or HIV
      1IIIB infection were tested. All sera showed significant neutralizing titers
      against HIV-1MN, in comparison with the low (when detectable) neutralizing titers
      against HIV-1IIIB. Competition assays revealed that the majority of HIV-1MN
      neutralizing Abs in patients' sera react with the V3 loop peptides. Only a small
      fraction of the total neutralizing capacity, presumably specific for other
      neutralizing epitopes, could not be adsorbed with HIV-1MN V3 loop peptides. The
      V3 loop peptides could also compete for the binding of Abs in patients' sera
      mediating Ab-dependent cellular cytotoxicity (ADCC) of HIV-1MN infected cells,
      inhibiting 30 to 80% of the ADCC activity. Finally, the HIV-1MN V3 loop MAP, when
      used as immunogen in the presence of RIBI adjuvant without a carrier protein,
      elicited Abs able to neutralize HIV-1MN (but not HIV-1IIIB) and to initiate ADCC
      of HIV-1MN-infected cells. This neutralizing and ADCC activity, mediated by V3MN
      specific rabbit Abs, could be totally absorbed by V3MN loop peptides.

PMID- 7519221
TI  - Method for systemic anaphylactic challenge in the rat using subplantar route.
AB  - Intravenous injection of antigen is the fastest and most effective way of
      eliciting anaphylactic shock in previously sensitized rats. When intravenous
      injection is difficult or undesirable, subplantar challenge is a preferable
      alternative to the intraperitoneal route.

PMID- 7519223
TI  - Efficacy of synthetic vaccines in the induction of cytotoxic T lymphocytes.
      Comparison of the costimulating support provided by helper T cells and lipoamino
      acid.
AB  - Synthetic vaccines that specifically induce active immunity mediated by cytotoxic
      T lymphocytes (CTL) are of great interest considering the central role of these
      cells in immune responses against intracellular antigens. The influence of
      specific T helper (Th) cell recruitment and of the potent immunostimulating
      lipoamino acid tripalmitoyl-S-glycerylcysteine (P3C) on CTL mediated immunity
      induced by CTL epitopes was analysed and compared. Synthetic peptides that
      represent CTL epitopes were found to be inefficient for CTL priming. However,
      when combined with peptides that contain Th cell epitopes, with proteins that
      carry multiple Th cell epitopes or with P3C, efficient priming of CTL was
      obtained. The costimulating support by P3C and proteins resulted in high
      cytolytic activities already after 9 days whereas, in the case of single helper
      epitopes, incubation periods of about 4 weeks were required. The effects of P3C
      and helper epitopes were additive.

PMID- 7519222
TI  - Conjugation of synthetic peptides to carrier iscoms: factors affecting the
      immunogenicity of the conjugate.
AB  - This study was designed to explore optimal conditions for the conjugation of a
      synthetic peptide to preformed influenza virus iscoms using MHS
      (maleimidohexanoyl-N-hydroxy-succinimide ester) as coupling agent. The peptide
      used in this study comprised amino acids 122-138 of porcine growth hormone (pGH).
      Different ratios of peptide to carrier iscoms were tested and the resulting
      conjugates were analysed for composition, antigenicity and immunogenicity. The
      problem of low solubility and poor immunogenicity of high-density peptide
      conjugates is discussed and a general protocol for conjugation of peptides to
      carrier iscoms is proposed.

PMID- 7519226
TI  - Antibody response to recombinant 65-kDa, 70-kDa and 18-kDa mycobacterial antigens
      in leprosy patients and healthy contacts in a leprosy-endemic population.
AB  - Antibody responses to recombinant Mycobacterium leprae 65-kDa (rML65) and 18-kDa
      (rML18), M. bovis BCG 65-kDa (rMB65) and M. tuberculosis 70-kDa (rMT70) antigens
      were measured by indirect ELISA in sera from leprosy patients and healthy
      contacts in a leprosy-endemic area in southern India. Antibody responses to M.
      leprae-specific epitopes on phenolic glycolipid-I (PGL-I) and a 35-kDa protein
      antigens also were measured simultaneously by PGL-I ELISA and the serum antibody
      competition test (SACT), respectively. Significantly higher levels of antibodies
      of the IgG isotype to rML65 and rMB65 were observed in bacterial index (BI)
      positive, lepromatous (LBI+) patients but not in other groups of leprosy patients
      and endemic controls [healthy family contacts (HFC), healthy hospital contacts
      (HHC), and healthy non-contacts (HNC)]. LBI+ patients could be distinguished from
      LBI- patients on the basis of their higher levels of IgG antibodies to rML65,
      rMB65 and rMT70; lower levels of IgM antibodies to these antigens and higher
      levels of anti-PGL-I IgM levels. In the former group, 84% were SACT positive in
      contrast to 39% in the latter groups. Among lepromatous patients good positive
      correlations were observed between IgG antibody responses to rML65 and rMB65 and
      anti-PGL-I IgM levels, SACT ID50 titers as well as BIs. Among healthy controls,
      HFC had higher levels of IgG antibodies to rML65, but lower levels to rMB65 than
      did HNC. Thirty-nine percent of the HFC were seropositive to anti-PGL-I IgM
      antibodies in contrast to 4% in the HNC. On the basis of these criteria, the
      immune profile of the HFC appears to be distinctly different from that of the
      HNC, even though both groups are from the same endemic area. It is therefore
      possible that antibody response to defined protein antigens of mycobacteria is
      influenced by the lesional bacterial load in leprosy patients and by exposure to
      homologous proteins of M. leprae and/or related environmental mycobacteria in the
      case of healthy contacts and noncontacts. The above results are discussed in
      relation to T- and B-cell activity toward M. leprae antigens and the
      immunoregulatory mechanisms of antibody production in leprosy.

PMID- 7519224
TI  - Pristane retards clearance of particulate materials from the peritoneal cavity of
      laboratory mice.
AB  - The effect of intraperitoneal pristane on the movement of India ink particles and
      water-based radio-opaque dye injected into the peritoneal cavity of mice was
      examined. There was a marked difference between pristane-treated mice and
      unmanipulated controls in terms of particle retention; unmanipulated mice cleared
      India ink particles via lymphatic drainage within 24 h following injection,
      whereas pristane-treated mice retained particles for as long as 22 days post
      injection. In contrast, all mice displayed similar kinetics of removal of radio
      opaque dye. We conclude that the movement of particulate matter from the
      peritoneal cavity is retarded in pristane-treated mice whereas removal of water
      based materials is unaffected. The implications for generation of ascites using
      hybridoma cells in pristane-primed mice is discussed.

PMID- 7519225
TI  - Detection and characterization of a lambda gt11 recombinant clone of M. leprae
      that expresses an antigenic determinant of a 64-kDa protein.
AB  - A genomic library of Mycobacterium leprae in the expression vector lambda gt11
      was screened with rabbit polyclonal hyperimmune antiserum elicited with a
      sonicated extract of M. leprae. Numerous reactive clones were isolated by this
      immunoscreening, indicating a broad antibody response of the rabbit. None of the
      recombinant clones was reactive with monoclonal antibodies to the previously well
      characterized M. leprae recombinant clones. One of the clones isolated, clone A,
      encoded a large, 132-143-kDa beta-galactosidase fusion protein expressing an
      epitope of M. leprae. Monospecific antibodies eluted from this fusion protein
      reacted on Western blots with a 64-kDa M. leprae protein. The DNA of this clone
      was shown to be distinct from the gene encoding the well-characterized
      immunodominant 65-kDa protein by DNA hybridization. We have identified a new
      lambda gt11 recombinant clone encoding a fusion protein with a 64-kDa protein.
      This protein is recognized by the humoral immune response of the rabbit in
      response to a challenge with an M. leprae cell extract.

PMID- 7519227
TI  - Fusion proteins with heterologous T helper epitopes. Recombinant E. coli heat
      stable enterotoxin proteins.
AB  - Fusion proteins containing specific B cell and T cell epitopes were used to
      examine how the intramolecular arrangement of T and B cell epitopes within a
      chimeric protein influences antigen-specific B cell antibody responses as well as
      specific T cell activation. Chimeric proteins, containing single or multiple
      copies of the Th epitope ovalbumin 323-339 (ova) linked at different positions to
      STa, the heat-stable enterotoxin of E. coli, were compared with respect to their
      ability to induce STa-specific antibody production and to induce ova-specific T
      cell activation. Chimeric proteins induced ova-dependent antibody production
      against STa at the amino terminal end, irrespective of the positioning of ova.
      Multiple tandem copies of ova in any position led to increased levels of antibody
      production against this epitope. In contrast, T cell help for antibody production
      against a second B cell epitope at the carboxy terminus of the fusion proteins
      was more effective after insertion of multiple copies of ova in a distal than in
      an adjacent position. A fusion protein, containing four copies of ova effectively
      elicited T cell help for antibody production against both examined B cell
      determinants, showing that activated Th cells recognizing a single epitope could
      simultaneously provide help for distinct sets of B cells specific for widely
      separated epitopes within a protein. T cell recognition of ova in all chimeric
      peptides, independently of its position, following the same pattern of genetic
      restriction (i.e. immunodominant in H-2d and nonimmunogenic in H-2k) as in the
      native ovalbumin molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519228
TI  - PhoE protein as a carrier for foreign epitopes.
AB  - Outer membrane protein PhoE of E. coli appears to be a suitable carrier for the
      expression of foreign antigenic determinants at the bacterial cell-surface.
      Insertion of stretches of amino acids in the cell-surface exposed regions of PhoE
      does not interfere with the biogenesis of the protein. Dependent on the cell
      surface exposed loop used for insertion and the character of the inserted amino
      acids up to 50 amino acids could be inserted. Both B-cell epitopes and T-cell
      epitopes remain antigenic and immunogenic in the PhoE-associated conformation.
      However, flanking amino acids can interfere with the antigenicity and
      immunogenicity of T-cell epitopes inserted in PhoE. Because E. coli PhoE can be
      expressed in attenuated Salmonella and Shigella strains, it seems to be a
      suitable vaccine carrier candidate.

PMID- 7519230
TI  - Hepatitis B virus core particles as a vaccine carrier moiety.

PMID- 7519229
TI  - Immunogenicity of viral B- and T-cell epitopes expressed in recombinant bacterial
      proteins.
AB  - Foreign polypeptides can be expressed as genetic inserts in several permissive
      sites of MalE and LamB, two Escherichia coli envelope proteins. Several viral B
      and T-cell epitopes have been inserted in these proteins and we analyzed the role
      of the molecular environment on the immunogenicity of the foreign epitopes. These
      studies demonstrated that the antigenicity and immunogenicity of B-cell epitopes
      depend on their site of insertion in the carrier protein. Using bacteria
      expressing B-cell epitopes either at the cell surface or in the periplasm, it was
      also shown that the cellular location of a foreign B-cell epitope expressed by
      recombinant bacteria determines its T-cell dependent or independent
      characteristics. Analysis of in vivo immunogenicity of purified LamB or MalE
      hybrid proteins expressing two different T-cell epitopes established that the
      immunogenicity of recombinant T-cell epitopes may be strongly affected by both
      the insertion site and inserted adjacent residues. The in vitro analysis of
      specific T-cell hybridoma response to hybrid MalE proteins also showed that the
      molecular context of a T-cell determinant alters the diversity of its T-cell
      recognition.

PMID- 7519231
TI  - Immune responses to epitopes inserted in Salmonella flagellin.
AB  - Plasmid pLS408 includes gene fliC(d) specifying Salmonella flagellin of antigenic
      type d with an in vitro deletion of a 48 base-pair EcoRV fragment in its central
      hypervariable antigenically-determinant region IV. Oligonucleotides specifying
      peptide epitopes of antigens of unrelated pathogens inserted, in correct
      orientation, at the unique EcoRV site of pLS408 specify chimeric flagellins and,
      in many instances, cause production of functional flagella when the plasmid is
      placed in a flagellin-deficient delta aroA live-vaccine strain of Salmonella
      dublin. The foreign epitope is then exposed at the surface of the flagellar
      filaments, as shown by the immobilizing effect of anti-epitope antibody and by
      immunogold electron-microscopy. The live-vaccine strain with a foreign epitope at
      the surface of its flagella when administered to mice by injection nearly always
      causes production of antibody with affinity for the foreign epitope and,
      sometimes, also for the source protein. Repeated injection of the live vaccine
      with an epitope of Streptococcus pyogenes type 5 M protein as insert caused
      production of opsonizing antibody and conferred partial protection against
      Streptococcus challenge. Injection of semi-purified chimeric flagella or
      flagellin, alone or with adjuvant, likewise causes antibody production, in one
      instance sufficient to give partial protection against influenza A virus
      challenge. Plasmid pLS408 with some inserts does not confer motility, either
      because the filaments produced are non-functional or because flagellin is made
      but not assembled or because little or no flagellin is produced. The features of
      a sequence which as insert determine production or non-production of functional
      flagella are not known. The effect of insertion of known T-cell epitopes and
      cellular immune responses to epitope inserts in flagellin are as yet little
      explored.

PMID- 7519232
TI  - Manipulation for the control of back pain and curve progression in patients with
      skeletally mature idiopathic scoliosis: two cases.
AB  - OBJECTIVE: This report of two cases illustrates the potential effect of
      chiropractic manipulative therapy on back pain and curve progression in the at
      risk, skeletally mature patient with adolescent idiopathic scoliosis. CLINICAL
      FEATURE: Two patients suffering from lumbar scoliosis and chronic back pain. Both
      had scoliosis that had progressed after skeletal maturity. INTERVENTION AND
      OUTCOME: Diversified type chiropractic manipulative therapy was used palliatively
      for back pain relief in one case, and routinely 1-2 times per month in the other
      case. The manipulation was applied manually, with the patients in the prone and
      side-posture positions. Vertebral levels manipulated were identified as
      fixated/dysfunctional segments based on static and/or motion palpation. They were
      generally applied to areas above and/or below the curve apex. When applied at the
      apex, cavitation was more easily achieved when the direction of thrust was into
      the concave side. This was also tolerated better by the patient. No attempt was
      made to "straighten the curve" by thrusting into the convex side. Gentle manual
      intersegmental mobilization, stretching and muscle massage techniques were also
      applied. The case treated palliatively had curve progression consistent with the
      literature over an 8-yr period. The case treated routinely did not. The procedure
      was effective in both cases for subjective relief of back pain. CONCLUSIONS:
      Diversified-type CMT has a favorable effect on acute back pain when used
      palliatively. The procedure may also have a favorable long term effect of
      preventing recurrence of back pain and on retarding curve progression when used
      routinely 1-2 times per month.

PMID- 7519233
TI  - Effects of dexamethasone on muscle protein homeostasis and on calpain and
      calpastatin activities and gene expression in rabbits.
AB  - The objectives were to investigate the mechanisms by which glucocorticoids
      control proteolysis in muscle cells and the relationship between the
      calpain:calpastatin system and proteolysis in muscle. Female rabbits were treated
      with 1 mg dexamethasone (Dex)/kg body weight per day for 0, 1, 2 or 4 days after
      which animals were killed and muscle samples taken for analyses. Dex reduced
      urinary N tau-methylhistidine (NMH) 48% (day 4 versus day 1 of Dex treatment) and
      muscle NMH concentrations by 49% (day 1) to 40% (day 2) respectively, suggesting
      that protein degradation was reduced. To investigate whether the changes in
      apparent proteolysis were related to calpains, we examined the effects of Dex on
      muscle calpain and calpastatin activities. These were unaffected by Dex. This
      implies that Dex-dependent changes in degradation are not mediated by changes in
      muscle calpain or calpastatin activities. We studied the effects of Dex on
      calpain and calpastatin gene expression as a means of clarifying the
      relationships between proteinase gene expression and proteinase activities. mu
      Calpain mRNA concentration was unaffected by Dex but m-calpain mRNA and
      calpastatin mRNA concentrations were reduced by 42-55% and 40% respectively. Dex
      had a similar effect on beta-actin mRNA. Although calpain and calpastatin genes
      behaved as house-keeping genes, changes in their expression mimicked apparent
      changes in proteolysis. The observation that calpain and calpastatin activities
      were unchanged indicates that additional regulation of the calpain:calpastatin
      system exists at other sites in muscle cells. To determine whether Dex-dependent
      changes in proteolysis were mediated indirectly, we assayed the effects of Dex on
      plasma thyroid hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519234
TI  - Role of 3', 5' cyclic adenosine monophosphate and protein kinase C in the
      regulation of insulin-like growth factor-binding protein secretion by thyroid
      stimulating hormone in isolated ovine thyroid cells.
AB  - Isolated sheep thyroid follicles release insulin-like growth factors (IGF)-I and 
      II together with IGF-binding proteins (IGFBPs). We previously showed that TSH
      suppresses the biosynthesis and release of IGFBPs in vitro which may increase the
      tissue availability of IGFs, allowing a synergy with TSH which potentiates both
      thyroid growth and function. Many of the actions of TSH on thyroid cell function
      are dependent upon activation of adenylate cyclase, although increased synthesis
      of inositol trisphosphate and activation of protein kinase C (PKC) have also been
      implicated. We have now examined whether probable changes in intracellular cyclic
      adenosine monophosphate (cAMP) or PKC are involved in TSH-mediated suppression of
      IGFBP release. Confluent primary cultures of ovine thyroid cells were maintained
      in serum-free Ham's modified F-12M medium containing transferrin, somatostatin
      and glycyl-histidyl-lysine (designated 3H), and further supplemented with sodium
      iodide (10(-8)-10(-3) mol/l), dibutyryl cAMP (0.25-1 mmol/l), forskolin (5-20
      mumol/l) or 12-O-tetradecanoylphorbol-13-acetate (TPA; 10(-11)-10(-6) mol/l),
      with or without exposure to TSH (200 microU/ml). The uptake and organification of
      Na [125I] by cells was examined after test incubations of up to 48 h, and IGFBPs
      in conditioned media were analysed by ligand blot using 125I-labelled IGF-II. The
      PKC activity in the cytosol and plasma membrane fractions of cells was measured
      by phosphorylation of histone using [gamma-32P]ATP, and PKC immunoreactivity was
      visualized by Western immunoblot analysis. While dibutyryl cAMP or forskolin
      largely reproduced the stimulatory effect of TSH on iodine organification, they
      did not mimic the inhibitory effect of TSH on the secretion of IGFBPs of 43, 34,
      28 and 19 kDa. Incubation with physiological or pharmacological concentrations of
      iodide (10(-6)-10(-3) mol/l) for up to 48 h significantly decreased TSH action on
      iodide uptake and organification but did not alter the inhibitory action of TSH
      on IGFBP release. Incubation of cells with 10(-11)-10(-6) mol TPA/l for 24 h
      inhibited the subsequent ability of TSH both to potentiate iodine organification
      and to suppress IGFBP release. In 3H medium, PKC activity was predominantly
      recovered from the membrane fraction but, following incubation for 48 h with TSH,
      the enzyme was no longer translocated to the membrane and was recovered
      predominantly from the cytosol.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7519235
TI  - Expression of IGFBP-1 in normal and cirrhotic human livers.
AB  - Cirrhosis of the liver, a condition characterised by hepatocyte regeneration, is
      also associated with elevated insulin levels and insulin resistance. In animal
      models hepatic regeneration is associated with increased IGFBP-1 gene expression.
      Insulin is known to be an inhibitor of IGFBP-1 gene expression and circulating
      insulin levels in man demonstrate a negative correlation with IGFBP-1 levels. To
      further our understanding of the regulation of IGFBP-1 in cirrhosis we have
      studied steady state levels of IGFBP-1 mRNA in human liver from three groups of
      patients: Group 1, tissue obtained at the time of harvesting donor liver for
      orthotopic liver transplantation (n = 4); group 2, patients undergoing major
      liver resection with no histological evidence of chronic liver disease (n = 4);
      and group 3, patients undergoing orthotopic transplantation for chronic liver
      failure (n = 9). Simultaneous samples of serum were taken at the time of surgery
      in some patients and in these patients IGFBP-1 mRNA levels were related to
      circulating levels of IGFBP-1 and insulin. IGFBP-1 mRNA was detectable in all the
      human liver samples with the greatest levels seen from the normal livers of group
      2 patients. Insulin levels were elevated in the cirrhotic group 3 patients
      compared to a normal range as were IGFBP-1 levels. There was no relationship
      between circulating levels of IGFBP-1 and IGFBP-1 gene expression. In conclusion,
      IGFBP-1 mRNA is present in human adult liver at the time of surgery and also in
      cirrhotic liver despite high levels of insulin suggesting that there are factors
      other than insulin regulating IGFBP-1 gene expression.

PMID- 7519236
TI  - Cytotoxicity of fresh NK1.1+ T cell receptor alpha/beta+ thymocytes against a
      CD4+8+ thymocyte population associated with intact Fas antigen expression on the
      target.
AB  - Recent studies have revealed that 10-20% of CD4+8- or CD4-8- thymocyte
      populations contain NK1.1+ T cell receptor (TCR)-alpha/beta+ cells. This
      subpopulation shows characteristics that are different from NK1.1- CD4+ or NK1.1-
      CD8+ T cells and seems to have developed in a manner different from NK1.1- T
      cells. Although extensive studies have been performed on the NK1.1+ TCR
      alpha/beta+ thymocytes, the physiological role of the NK1.1+ TCR-alpha/beta+
      thymocytes has been totally unclear. In the present study, we found that freshly
      isolated NK1.1+ TCR-alpha/beta+ thymocytes, but neither whole thymocytes nor
      lymph node T cells, directly killed CD4+8+ thymocytes from normal syngeneic or
      allogeneic mice by using a long-term cytotoxic assay in which flow cytometry was
      used to detect the cytotoxicity. However, only weak cytotoxicity was detected
      against thymocytes from lpr mice on which the Fas antigen that transduces signals
      for apoptosis into the cells is not expressed. Furthermore, the NK1.1+ TCR
      alpha/beta+ thymocytes exhibited high cytotoxicity against T lymphoma targets
      transfected with fas genes as compared with the parental T lymphoma targets or
      target cells transfected with mutated fas genes, which lack the function of
      transducing signals. On the other hand, NK1.1+ effector thymocytes from gld mice
      that carry a point mutation in Fas ligand did not kill thymocyte targets from
      normal mice. The present findings, thus, consistently suggest that the NK1.1+ TCR
      alpha/beta+ thymocytes kill a subpopulation among CD4+8+ thymocytes via Fas
      antigen and in this way regulate generation of T lineage cells in the thymus.

PMID- 7519237
TI  - Dual role of the p75 tumor necrosis factor (TNF) receptor in TNF cytotoxicity.
AB  - Whereas there is ample evidence for involvement of the p55 tumor necrosis factor
      (TNF) receptor (p55-R) in the cytocidal effect of TNF, the role of the p75 TNF
      receptor (p75-R) in this effect is a matter of debate. In this study, we probed
      the function of p75-R in cells sensitive to the cytotoxicity of TNF using a wide
      panel of antibodies (Abs) against the receptor's extracellular domain. Two
      distinct Ab effects were observed. The Abs triggered signaling for cytotoxicity.
      This effect: (a) was correlated with the extent of p75-R expression by the cells;
      (b) was dependent on receptor cross-linking by the Abs; (c) occurred in HeLa
      cells, but not in A9 cells transfected with human p75-R or in HeLa cells
      expressing cytoplasmically truncated p75-R mutants, indicating that it involves
      cell-specific activities of the intracellular domain of the receptor; (d) was
      synergistic with the cytocidal effect of Abs against p55-R. Moreover, it seemed
      to reverse induced desensitization to the cytocidal effect of anti p55-R Abs,
      suggesting that it involves mechanisms different from those of the signaling by
      the p55 TNF-R. In addition, the Abs affected the response to TNF in a way that
      does not involve the signaling activity of p75-R. These effects: (a) could be
      observed also in cells in which only p55-R signaled for the cytocidal effect; (b)
      were not dependent on receptor cross-linking by the Abs; (c) varied according to
      the site at which the Abs bound to the receptor; and (d) were correlated
      inversely with the effects of the Abs on TNF binding to p75-R. That is, Abs
      binding to the membrane-distal part of the receptor's extracellular domain
      displaced TNF from the p75 receptor and enhanced cytocidal effect, whereas Abs
      that bind to the membrane-proximal part of the extracellular domain--a region at
      which a conformational change seems to take place upon TNF binding--decreased the
      dissociation of TNF from p75-R and inhibited its cytocidal effect. The above
      findings suggest that p75-R contributes to the cytocidal effect of TNF both by
      its own signaling and by regulating the access of TNF to p55-R.

PMID- 7519238
TI  - Deletion within the Src homology domain 3 of Bruton's tyrosine kinase resulting
      in X-linked agammaglobulinemia (XLA).
AB  - The gene responsible for X-linked agammaglobulinemia (XLA) has been recently
      identified to code for a cytoplasmic tyrosine kinase (Bruton's agammaglobulinemia
      tyrosine kinase, BTK), required for normal B cell development. BTK, like many
      other cytoplasmic tyrosine kinases, contains Src homology domains (SH2 and SH3),
      and catalytic kinase domain. SH3 domains are important for the targeting of
      signaling molecules to specific subcellular locations. We have identified a
      family with XLA whose affected members have a point mutation (g-->a) at the 5'
      splice site of intron 8, resulting in the skipping of coding exon 8 and loss of
      21 amino acids forming the COOH-terminal portion of the BTK SH3 domain. The study
      of three generations within this kinship, using restriction fragment length
      polymorphism and DNA analysis, allowed identification of the mutant X chromosome
      responsible for XLA and the carrier status in this family. BTK mRNA was present
      in normal amounts in Epstein-Barr virus-induced B lymphoblastoid cell lines
      established from affected family members. Although the SH3 deletion did not alter
      BTK protein stability and kinase activity of the truncated BTK protein was
      normal, the affected patients nevertheless have a severe B cell defect
      characteristic for XLA. The mutant protein was modeled using the normal BTK SH3
      domain. The deletion results in loss of two COOH-terminal beta strands containing
      several residues critical for the formation of the putative SH3 ligand-binding
      pocket. We predict that, as a result, one or more crucial SH3 binding proteins
      fail to interact with BTK, interrupting the cytoplasmic signal transduction
      process required for B cell differentiation.

PMID- 7519240
TI  - Fas and tumor necrosis factor receptor-mediated cell death: similarities and
      distinctions.
AB  - Fas antigen and two tumor necrosis factor receptors (TNFR), p55 and p75, are
      implicated in the triggering of cell death upon stimulation by natural ligands
      and specific monoclonal antibodies. However, the relative efficiency of each
      receptor, the mechanisms that regulate their function and the signaling pathways
      they employ, remain to be elucidated. In this study, fusion proteins, composed of
      the extracellular domain of CD40 and the intracellular and transmembrane domains
      of Fas, TNFRp55 and TNFRp75, were stably expressed in a human melanoma cell line
      that is deficient in Fas and TNFR expression. Transfectants were stimulated by a
      soluble recombinant form of the CD40 ligand gp39, and the effect on cell
      viability determined. Engagement of all three fusion proteins by the gp39 ligand
      induced lethal signals, but the rate at which cell death occurred was distinct.
      Fas-derived signals were observed to have the most rapid effect, killing most
      cells within hours of stimulation, whereas TNFRp55- and TNFRp75-associated
      signals resulted in cell death within 2-3 d after engagement by ligand. It is
      interesting to note that optimal cell killing by all three fusion proteins was
      dependent on a critical, low to intermediate, cell surface expression level. High
      levels of fusion protein expression, on the other hand, were associated with
      inhibition of cell death. Our results provide a model to study Fas and TNFR
      mediated cell death and suggest a novel mechanism for the regulation of death
      signals triggered by members of the TNFR family.

PMID- 7519239
TI  - Downregulation of peptide transporter genes in cell lines transformed with the
      highly oncogenic adenovirus 12.
AB  - The expression of class I major histocompatibility complex antigens on the
      surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and
      correlates with the high oncogenicity of this virus. In primary embryonal
      fibroblasts from transgenic mice that express both endogenous H-2 genes and a
      miniature swine class I gene (PD1), Ad12-mediated transformation results in
      suppression of cell surface expression of all class I antigens. Although class I
      mRNA levels of PD1 and H-2Db are similar to those in nonvirally transformed
      cells, recognition of newly synthesized class I molecules by a panel of
      monoclonal antibodies is impaired, presumably as a result of inefficient assembly
      and transport of the class I molecules. Class I expression can be partially
      induced by culturing cells at 26 degrees C, or by coculture of cells with class I
      binding peptides at 37 degrees C. Analysis of steady state mRNA levels of the
      TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that
      they both are significantly reduced, TAP2 by about 100-fold and TAP1 by 5-10
      fold. Reconstitution of PD1 and H-2Db, but not H-2Kb, expression is achieved in
      an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1,
      expression construct. From these data it may be concluded that suppressed
      expression of peptide transporter genes, especially TAP2, in Ad12-transformed
      cells inhibits cell surface expression of class I molecules. The failure to fully
      reconstitute H-2Db and H-2Kb expression indicates that additional factors are
      involved in controlling class I gene expression in Ad12-transformed cells.
      Nevertheless, these results suggest that suppression of peptide transporter genes
      might be an important mechanism whereby virus-transformed cells escape immune
      recognition in vivo.

PMID- 7519241
TI  - Identification of a common T/natural killer cell progenitor in human fetal
      thymus.
AB  - The phenotypic similarities between natural killer (NK) and T cells have led to
      the hypothesis that these distinctive lymphocyte subsets may be developmentally
      related and thus may share a common progenitor (Lanier, L. L., H. Spits, and J.
      H. Phillips, 1992. Immunol. Today. 13:392; Rodewald, H.-R., P. Moingeon, J. L.
      Lurich, C. Dosiou, P. Lopez, and E. L. Reinherz. 1992. Cell. 69:139). In this
      report, we have investigated the potential of human CD34+ triple negative
      thymocytes ([TN] CD3-, CD4-, CD8-) to generate both T cells and NK cells in
      murine fetal thymic organ cultures (mFTOC) and in vitro clonogenic assays. CD34+
      TN thymocytes, the majority of which express prominent cytoplasmic CD3 epsilon
      (cytoCD3 epsilon) protein, can be divided into high (CD34Bright) and low
      (CD34Dim) surface expressing populations. CD34Bright TN thymocytes were capable
      of differentiating into T and NK cells when transferred into mFTOC, and
      demonstrated high NK cell clonogenic capabilities when cultured in interleukin
      (IL)-2, IL-7, and stem cell factor (SCF). Likewise, CD34Bright TN thymocyte
      clones after 5 d in culture were capable of generating NK and T cells when
      transferred into mFTOC but demonstrated clonogenic NK cell differentiation
      capabilities when maintained in culture with IL-2. CD34Dim TN thymocytes,
      however, possessed only T cell differentiation capabilities in mFTOC but were not
      expandable in clonogenic conditions containing IL-2, IL-7, and SCF. No
      significant differentiation of other cell lineage was detected in either mFTOC or
      in clonogenic assays from CD34+ TN thymocytes. These results represent the first
      definitive evidence of a common T/NK cell progenitor in the human fetal thymus
      and delineate the point in thymocyte differentiation where T and NK cells
      diverge.

PMID- 7519243
TI  - Monoclonal antibodies defining functional sites on the toxin superantigen
      staphylococcal enterotoxin B.
AB  - Four monoclonal antibodies (mAbs) were produced binding to four nonoverlapping
      epitopes on the superantigen staphylococcal enterotoxin B (SEB). The mAbs were
      tested for their ability to detect SEB bound to major histocompatibility complex
      (MHC) class II, to inhibit SEB binding to MHC class II, to inhibit SEB
      stimulation of T cell hybridomas, to bind to various nonfunctional mutants of
      SEB, and to capture and present SEB and its mutants to T cells in the absence of
      MHC class II. We concluded that two mAbs, B344 and B327, bound to epitopes not
      required for superantigen function, one mAb, 2B33, blocked an MHC interaction
      site on SEB, and the fourth mAb, B87, blocked the T cell recognition site on SEB.
      Moreover, two mAbs (B344 and 2B33) were capable of presenting SEB, although much
      less efficiently than APC, to CD4- but not CD4+ T cell hybridomas. The results
      confirm the functional domains on SEB originally defined by mutation and show
      that MHC class II is not always an essential component of the superantigen
      ligand.

PMID- 7519242
TI  - Higher autoantibody levels and recognition of a linear NH2-terminal epitope in
      the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent
      diabetes mellitus.
AB  - The smaller form of the GABA-synthesizing enzyme glutamic acid decarboxylase
      (GAD65) is a major autoantigen in two human diseases that affect its principal
      sites of expression. Thus, destruction of pancreatic beta cells, which results in
      insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic
      transmission in Stiff-Man syndrome (SMS) are both characterized by circulating
      autoantibodies to GAD65. Anti-GAD65 autoantibodies in IDDM are predominantly
      directed to conformational epitopes. Here we report the characterization of
      humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also
      had IDDM. All SMS patients immunoprecipitated native GAD65 and the main titers
      were orders of magnitude higher than in IDDM patients. Furthermore, in contrast
      to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients
      recognized denatured GAD65 on Western blots. Two major patterns of epitope
      specificity were identified on Western blots. The first pattern, detected in 25
      of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive
      with a linear NH2-terminal epitope residing in the first eight amino acids of
      GAD65. Nine of nine individuals who were HLA-haplotyped in this group carried an
      IDDM susceptibility haplotype and HLA-DR3, DQw2 was particularly abundant. The
      second pattern, detected in 10 of 35 patients (29%) of whom two had IDDM (20%),
      included reactivity with the NH2-terminal epitope plus strong reactivity with one
      or more additional epitope(s) residing COOH-terminal to amino acid 101. The
      second epitope pattern may represent epitope spreading in the GAD65 molecule, but
      may also include some cases of epitope recognition associated with IDDM resistant
      HLA-haplotypes. The principal NH2-terminal linear epitope in GAD65 distinguishes
      the reactivity of SMS and IDDM autoantibodies and may be a determinant of
      pathogenicity for GABA-ergic neurons. The greater magnitude and distinct
      specificity of the humoral response to GAD65 in SMS may reflect a biased
      involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody
      responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and
      cytotoxic T cell responses.

PMID- 7519245
TI  - Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and
      function.
AB  - Antigen-specific T cell activation requires the engagement of the T cell receptor
      (TCR) with antigen as well as the engagement of appropriate costimulatory
      molecules. The most extensively characterized pathway of costimulation has been
      that involving the interaction of CD28 and CTLA4 on the T cell with B7 (now
      termed B7-1) on antigen presenting cells. Recently, B7-2 a second costimulatory
      ligand for CTLA4, was described, demonstrating the potential complexity of
      costimulatory interactions. This report examines and compares the expression and
      function of B7-1 and B7-2. Overall these results indicate that (a) B7-1 and B7-2
      can be expressed by multiple cell types, including B cells, T cells, macrophages,
      and dendritic cells, all of which are therefore candidate populations for
      delivering costimulatory signals mediated by these molecules; (b) stimulating B
      cells with either LPS or anti-IgD-dextran induced expression of both B7-1 and B7
      2, and peak expression of both costimulatory molecules occurred after 18-42 h of
      culture. Expression of B7-2 on these B cell populations was significantly higher
      than expression of B7-1 at all times assayed after stimulation; (c) blocking of
      B7-2 costimulatory activity inhibited TCR-dependent T cell proliferation and
      cytokine production, without affecting early consequences of TCR signaling such
      as induction of CD69 or interleukin 2 receptor alpha (IL-2R alpha); and (d)
      expression of B7-1 and of B7-2 can be regulated by a variety of stimuli.
      Moreover, expression of B7-1 and B7-2 can be independently regulated by the same
      stimulus, providing an additional complexity in the mechanisms available for
      regulating costimulation and hence immune response.

PMID- 7519246
TI  - Arterial smooth muscle cells express nitric oxide synthase in response to
      endothelial injury.
AB  - Endothelial cells regulate vascular tone by secreting paracrine mediators that
      control the contractility of arterial smooth muscle cells. Nitric oxide (NO) is
      an important vasodilating agent that is generated from L-arginine by the enzyme
      nitric oxide synthase (NOS), which is expressed constitutively by the
      endothelium. NO also inhibits platelet aggregation, contributing to the
      antithrombotic properties of the endothelial surface. It would therefore be
      expected that loss of the endothelium during arterial injury would lead to
      vasospasm and thrombosis but instead, the neointima formed after injury has a
      nonthrombogenic surface and a maintained vascular patency. We report here that
      arterial smooth muscle cells in the neointima formed after a deendothelializing
      balloon injury to the rat carotid artery express the cytokine-inducible isoform
      of NOS. Expression was detectable by reverse transcription-polymerase chain
      reaction from day 1-14 after injury and in situ hybridization showed expression
      of NOS mRNA by neointimal smooth muscle cells, particularly at the surface of the
      lesion. This was associated with systemically detectable NO production as
      revealed by electron paramagnetic resonance spectroscopic analysis of
      nitrosylated red cell hemoglobin. Local NO production by intimal smooth muscle
      cells after endothelial injury could represent an important mechanism for the
      maintenance of arterial patency and nonthrombogenicity in the injured artery.

PMID- 7519247
TI  - Characterization of neutralization epitopes on the VP7 surface protein of
      serotype G11 porcine rotaviruses.
AB  - Rotavirus strain A253, isolated from the faeces of a diarrhoeic piglet in
      Venezuela, was classified as serotype G11 by cross-neutralization studies and by
      comparison of the deduced amino acid sequence of the VP7 surface protein. The
      epitopes involved in neutralization of the two G11 porcine rotavirus strains A253
      and YM were analysed using neutralization-resistant mutants selected with seven
      neutralizing monoclonal antibodies (MAbs), monotype-specific (M-) MAbs and
      serotype-specific (S-) MAbs, produced against VP7 of strain A253. Cross
      neutralization tests and sequence analysis of the escape mutants selected from
      strains A253 and YM indicated the presence of two antigenic sites, one common to
      both M-MAbs and S-MAbs in region A (positions 87, 91 and 96) and the other
      defined by one S-MAb in region C (position 223). All A253 variants selected with
      M-MAbs and two S-MAbs, although having different amino acid substitutions, had a
      change at amino acid position 87, whereas YM variants involved residues 91 and
      96, part of the same antigenic site. Compared to strain A253, the YM stain
      presents an amino acid substitution at position 87 and was not recognized by M
      MAbs. These results suggest that in the VP7 of G11 serotype specificity, the
      amino acid at position 87 is an important component of a neutralization site
      associated with region A and the intraserotypic variation between strains A253
      and YM may account for the selection of mutations at different positions by a
      single MAb.

PMID- 7519248
TI  - Initiation of reverse transcription during cell-to-cell transmission of human
      immunodeficiency virus infection uses pre-existing reverse transcriptase.
AB  - H3B cells, a laboratory clone of H9 cells persistently infected with the HTLV
      IIIB strain of human immunodeficiency virus (HIV), contained significant levels
      of cell-associated reverse transcriptase (RT) activity measured by in vitro
      assays using either exogenous or endogenous templates. The cell-associated RT
      activity detected using exogenous template was almost wholly in a soluble (non
      sedimentable) form whereas endogenous activity sedimented as a particulate
      structure associated with viral RNA. Despite this, H3B cells did not contain
      episomal HIV DNA detectable by Southern blot, indicating that in vivo reverse
      transcription was not occurring to any significant extent in these cells.
      However, when susceptible HUT 78 cells were infected by co-cultivation with H3B
      cells, dramatic synthesis of episomal HIV DNA occurred. Concurrently with this de
      novo initiation of reverse transcription, however, we found no detectable change
      in intracellular levels or cleavage profiles of immunoprecipitable RT
      polypeptides. Finally, actinomycin D pre-treatment of H3B cells to prevent de
      novo transcription from donor cell proviral DNA after co-cultivation did not
      affect the initiation of in vivo reverse transcription following cell-to-cell HIV
      infection. These results demonstrated that cells persistently infected with HIV
      contained significant fully cleaved cell-associated RT in a form that was active
      in vitro but not in vivo and that following cell-to-cell transmission of HIV
      infection to susceptible cells, de novo reverse transcription was initiated
      without detectable evidence of further synthesis or proteolytic processing of HIV
      RT. The nature of this initiation process requires further study.

PMID- 7519250
TI  - Changes in antibody titers to hepatitis C virus following interferon therapy for
      chronic infection.
AB  - The use of quantitative assays for hepatitis C virus specific antibodies (anti
      HCV) as a prognostic marker was evaluated in 31 patients with chronic hepatitis C
      treated with interferon (IFN). Changes in titers of serum HCV-RNA and anti-HCV
      antibodies; anti-C11 (anti-core), anti-C100 (anti-NS3), and anti-C7 (anti-NS3)
      were investigated. Recombinant IFN-alpha 2a was administered and the patients
      were followed for more than 1 year. The patients were classified into three
      groups according to their responses to IFN: 11 sustained responders with
      continuous normalizations of serum alanine aminotransferase (ALT) levels; 14
      transient responders with transient decreases in ALT; and six nonresponders who
      had no changes in ALT levels. Ten of 11 sustained responders had a continuous
      decrease in anti-C11 titers after completion of treatment, decreasing to less
      than half of pretreatment titers. No patients in the other two groups had a
      continuous decrease in anti-C11 titers. Although sustained responders had
      decreases in anti-C100 and anti-C7 titers after IFN therapy, these titers also
      decreased in some patients in the other two groups. HCV-RNA was not detected in
      the sera of 10 of 11 sustained responders following IFN therapy. In contrast,
      while 9 of 10 transient and non-responders had a decrease or disappearance of HCV
      RNA at the completion of therapy, they had increased levels thereafter. These
      results indicate that anti-HCV-core (anti-C11) titers most closely reflect the
      status of HCV replication. A quantitative assay for anti-HCV-core antibody can be
      used as a predictive marker of remission in IFN-treated patients with chronic
      hepatitis C.

PMID- 7519244
TI  - Mapping functional regions in the lumenal domain of the class II-associated
      invariant chain.
AB  - The MHC class II-associated invariant chain interacts in trimeric form with class
      II molecules, inhibits peptide binding, and mediates targeting of class II
      molecules to endosomal compartments. To dissect the different functions of the
      invariant (Ii) chain, a set of cDNAs, encoding truncated forms of the Ii chain,
      was constructed. mRNAs, transcribed from these cDNAs were translated in vitro,
      together with mRNAs encoding class II HLA DR1 alpha and beta subunits. An Ii
      chain truncation that contains the 104 NH2-terminal amino acids was able to
      associate with class II molecules. This construct contains the region from which
      class II-associated Ii chain peptides (CLIP, amino acids 81-104) are derived. The
      absence of a further eight residues at the COOH terminus results in a construct
      of 96 amino acids that is unable to associate with class II molecules.
      Association of the truncated Ii chains with class II molecules showed a strict
      correlation with inhibition of peptide binding. Removal of the NH2-terminal
      cytoplasmic tail and transmembrane region of Ii chain and its replacement with a
      cleavable signal sequence led to aberrant folding and impaired association with
      class II molecules. The region between amino acids 163 and 183 was found to be
      essential for visualization of Ii chain homotrimers by covalent cross-linking.

PMID- 7519249
TI  - Analysis of murine antibody responses to baculovirus-expressed human
      immunodeficiency virus type 1 envelope glycoproteins.
AB  - An analysis of the humoral immunogenicity of a candidate AIDS vaccine (VaxSyn) in
      a murine model system is presented. Sera taken from a panel of mice immunized
      with the immunogen were analysed for their ability to bind a panel of gp120
      representing peptides and limited reactivity to known sites of immunological
      interest was observed. Monoclonal antibodies (MAbs) were characterized as binding
      to a more restricted variety of regions on gp120 including C1, V2, V4 and the C
      terminus. A tetrazolium-based cytocidicity assay was used and shown to be an
      effective and objective method for the screening of human immunodeficiency virus
      (HIV)-neutralizing activity in large numbers of samples. None of the MAbs
      characterized in this study neutralize HIV-1 reference strains. The significance
      of these findings in view of previous publications is discussed.

PMID- 7519251
TI  - Detection of the putative E2 protein of hepatitis C virus in human liver.
AB  - The question was asked whether a predicted envelope protein, considered to be
      processed from the polyprotein precursor encoded by the putative E2/NS1 region of
      the hepatitis C virus (HCV) genome, may be observed in HCV-infected humans. Two
      polyclonal antibodies against recombinant E2/NS1 proteins were prepared and their
      reactivity tested against liver extracts from HCV-infected patients by
      immunoblotting analysis. A band corresponding to a size of 44 kDa was detected in
      liver extracts from patients who were positive for the HCV-specific antibody anti
      C100-3 but not in liver extracts from patients who did not have anti-C100-3
      antibody. Additionally, no band was detected using preimmune sera or antisera
      which had been preabsorbed with recombinant E2/NS1 proteins. Deglycosylation
      studies demonstrated that the 44 kDa protein was a glycosylated form of a 38 kDa
      protein which corresponds to the predicted molecular weight of the putative
      E2/NS1 protein. These results suggest that the 44 kDa protein is a product of the
      E2/NS1 region. Frequent observation of the 44 kDa band in cases of chronic active
      hepatitis C suggests a correlation between the expression of this protein and the
      progression of hepatitis.

PMID- 7519252
TI  - Antibodies and viremia in acute post-transfusion hepatitis C: a prospective
      study.
AB  - Fourteen patients who developed acute post-transfusion hepatitis C after open
      heart surgery were studied for seroconversion, viremia, and aminotransferase.
      Anti-HCV antibodies were measured by first and second generation ELISA and became
      positive between one week and more than 6 months after infection. Seroconversion
      in four patients and passively transfused antibodies were only found by the
      second generation assay, indicating its significantly higher sensitivity. Viremia
      was detected by reverse transcription and the polymerase chain reaction within
      the first 4 weeks of infection in 13 patients and persisted for more than 2 years
      in all of them. One patient died of cardiac cause. Viral strains were
      heterogeneous between the different patients, but showed no significant variation
      within one patient during the course of hepatitis deduced from the results with
      different sets of oligonucleotides. Viremia preceded hepatitis by 4 weeks,
      seroconversion determined by ELISA II followed after an 8 week interval, and anti
      C-100 antibodies appeared 26 weeks later. Aminotransferase activities returned to
      normal values in 10 patients.

PMID- 7519253
TI  - A dramatic change in the interaction of Cu(II) with bio-peptides promoted by SDS-
      a model for complex formation on a membrane surface.
AB  - The extent of complex formation between Cu(II) and many biologically active
      oligopeptides has been shown to change significantly in the presence of SDS
      micelles, a recognized model for cell lipid membranes. Protonation constants of
      peptides can be increased by up to 2 log unit, especially when they contain
      hydrophobic side chains. Metal complex formation is generally less extensive and
      the conformations of peptides can be altered dramatically when compared to those
      in simple aqueous solution.

PMID- 7519254
TI  - Plasticity in the adult human oligodendrocyte lineage.
AB  - Preoligodendrocytes have been described in cultures and tissue prints of adult
      human white matter (Armstrong et al., 1992). To characterize further these
      precursors of human oligodendrocytes, we have investigated whether they express
      genes playing a critical role in oligodendrocyte development. In the intact human
      brain, platelet-derived growth factor receptor alpha (PDGF alpha R) and myelin
      transcription factor 1 (MyTI) transcripts are expressed in 1-2% of cells of the
      oligodendrocyte lineage (OL), and clusters of such cells can be found in the
      periventricular region. Myelin basic protein transcripts containing exon 2
      information (exon 2+ MBP), which are characteristic of the premyelinating stage,
      are detected in 15-20% of OL cells in vivo. When OL cells are separated from
      human white matter and allowed to regenerate in vitro, a much larger proportion
      of these cells express developmentally regulated genes, while exon 2- MBP and
      proteolipid protein (PLP) transcripts characteristic of mature OL cells appear
      transiently downregulated. Basic fibroblast growth factor (bFGF), even in the
      presence of PDGF, does not promote DNA synthesis in these cultured OL cells. Yet
      bFGF induces human oligodendrocytes to regenerate their processes rapidly in
      vitro and to express O4 antigens as well as exon 2+ MBP, MyTI, and PLP
      transcripts. While bFGF accelerates early regenerative processes, it also
      maintains high expression of exon 2+ MBP transcripts in OL cells for up to 2
      weeks in vitro. In contrast, high levels of insulin in the absence of bFGF allow
      accumulation of exon 2- MBP and PLP transcripts in most OL cells at 2-3 weeks in
      vitro. We propose that the myelinated human brain harbors a small pool of
      precursors of oligodendrocytes and that growth factor-regulated phenotypic
      plasticity rather than mitogenic potential accounts for the regeneration of
      oligodendrocytes in the initial stages of demyelinating diseases such as multiple
      sclerosis.

PMID- 7519255
TI  - Ionic currents of Kenyon cells from the mushroom body of the honeybee.
AB  - The mushroom bodies have been suggested to be essentially involved in learning
      and memory in insects. In the honeybee Apis mellifera they are composed of about
      340,000 intrinsic elements, called Kenyon cells, which can be easily separated
      from all other neurons of the brain. Here we describe a preparation in which we
      studied ionic currents in the isolated Kenyon cell somata, using tight-seal whole
      cell recording. Several outward and inward currents were identified and
      investigated by the use of pharmacological agents and in ion substitution
      experiments: a rapidly inactivating A-type potassium current that is completely
      blocked with 5 mM 4-aminopyridine; a calcium-activated potassium current that is
      blocked by 1-100 nM charybdotoxin; a delayed rectifier-type potassium current
      that is only weakly sensitive to tetraethylammonium but is blocked by 100 microM
      quinidine; a rapidly activating and inactivating, TTX-sensitive sodium current; a
      persistent sodium current that is both TTX and cadmium sensitive; and a calcium
      current that is completely blocked at 50 microM cadmium and is affected by
      verapamil and nifedipine only at high concentrations (100 microM). The currents
      described here are very similar to currents found in other insect neurons or
      muscle cells. This preparation will not only facilitate studies concerning the
      action of transmitters and neuromodulators that are contained within neurons
      converging onto the Kenyon cells, but will also allow a study of the role of the
      adenylyl cyclase pathway, elements of which are expressed in Kenyon cells, and
      are known to be essential for learning in invertebrates.

PMID- 7519256
TI  - Tenascin demarcates the boundary between the myelinated and nonmyelinated part of
      retinal ganglion cell axons in the developing and adult mouse.
AB  - The molecular determinants controlling the topographically restricted
      distribution of neural cells in the mammalian CNS are largely unknown. In the
      mouse, myelin-forming oligodendrocytes are differentially distributed along
      retinal ganglion cell axons. These axons are myelin free intraretinally and in
      the most proximal (i.e., retinal) part of the optic nerve, but become myelinated
      in the distal (i.e., chiasmal) part of the optic nerve. Tenascin protein and mRNA
      are detectable in increased amounts at the retinal end of the developing optic
      nerve before the arrival of oligodendrocyte progenitor cells and are restricted
      to this region in the adult optic nerve. Tenascin is a nonadhesive substrate for
      oligodendrocytes and their progenitor cells in vitro when offered as a substrate
      in choice with polyornithine. These observations suggest that tenascin is
      critical for the establishment and maintenance of the restricted distribution of
      myelin-forming oligodendrocytes along retinal ganglion cell axons of the mouse.

PMID- 7519257
TI  - Dopaminergic regulation of the serotonergic raphe-striatal pathway: microdialysis
      studies in freely moving rats.
AB  - Morphological evidence demonstrates the existence of dopaminergic afferent
      pathways and dopamine (DA)-containing neurons in the dorsal raphe nucleus (DRN).
      In a recent report, a DA D2-like receptor-mediated regulation of serotonin (5-HT)
      extracellular concentration in DRN has been found. Given the existence of
      somatodendritic 5-HT1A autoreceptors in the DRN, changes of the extracellular
      concentration of 5-HT in the vicinity of cell bodies and dendrites may be
      relevant for the control of the activity of ascending serotonergic pathways. In
      the present brain microdialysis study we have used a chromatographic method
      (HPLC) enabling the simultaneous measurement of DA, 5-HT, and their main
      metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5
      HIAA). The presence of a neuronal pool of DA within the DRN was revealed by the
      local infusion of amphetamine (10 microM), which significantly increased the
      extracellular concentration of both amines. The local striatal infusion (10
      microM) of the selective DA D1-like agonist SKF-38393, the selective DA D2-like
      agonist quinpirole (LY 171,555), or the nonselective DA agonist apomorphine
      markedly decreased DA and DOPAC extracellular concentrations and failed to modify
      5-HT or 5-HIAA in the striatum, indicating the lack of terminal (striatal)
      control of 5-HT release by dopaminergic transmission. In contrast, the systemic
      administration of apomorphine (2.8 mumol/kg, s.c.) significantly increased the
      extracellular concentration of 5-HT in the DRN and decreased it in the striatum.
      The reduction of striatal 5-HT extracellular concentration was prevented by the
      previous administration of the selective 5-HT1A receptor antagonist WAY 100135
      (17.6 mumol/kg, s.c.), which by itself did not change extracellular 5-HT in
      striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519258
TI  - Prostaglandin E2 enhances bradykinin-stimulated release of neuropeptides from rat
      sensory neurons in culture.
AB  - Prostaglandins are known to enhance the inflammatory and nociceptive actions of
      other chemical mediators of inflammation such as bradykinin. One possible
      mechanism for this sensitizing action is that prostanoids augment the release of
      neuroactive substances from sensory neurons. To initially test this hypothesis,
      we examined whether selected prostaglandins could enhance the resting or
      bradykinin-evoked release of immunoreactive substance P (iSP) and/or
      immunoreactive calcitonin gene-related peptide (iCGRP) from sensory neurons in
      culture. Bradykinin alone causes a concentration-dependent increase in the
      release of iSP and iCGRP from isolated sensory neurons, and this action is
      abolished in the absence of extracellular calcium. Pretreating the neurons with
      PGE2 (10 nM to 1 microM) potentiates the bradykinin-evoked release of both iSP
      and iCGRP by approximately two-to fourfold. At these concentrations, PGE2 alone
      did not significantly alter peptide release. Exposing the cultures to 1 microM
      PGF2 alpha is ineffective in altering either resting or bradykinin-evoked peptide
      release. Sensory neurons in culture contain cyclooxygenase-like immunoreactivity
      suggesting that the enzyme that converts arachidonic acid to prostaglandins is
      present. In addition, pretreating cultures with 14C-arachidonic acid yields
      radiolabeled eicosanoids that cochromatograph with known prostaglandin standards.
      Preexposing cultures to indomethacin abolishes the production of prostaglandins
      and attenuates the bradykinin-stimulated release of iSP and iCGRP. This implies
      that the synthesis of prostaglandins contributes to the bradykinin-evoked release
      of peptides. The augmentation of bradykinin-induced release of iSP and iCGRP by
      PGE2 may be one mechanism to account for the inflammatory and hyperalgesic
      actions of this eicosanoid.

PMID- 7519260
TI  - Mapping of antigenic epitopes within the recombinant human preproinsulin related
      to insulin-dependent diabetes mellitus.
AB  - The human insulin domains, signal peptide, B-chain, C-peptide, and A-chain, were
      highly expressed in Escherichia coli as recombinant proteins N-terminally fused
      to glutathione-S-transferase and a histidine-hexapeptide. The recombinant
      proteins were purified from insoluble cell fraction by affinity chromatography
      using metal chelating matrix, which was charged with Ni+2 ions. ELISA screening
      for autoantibodies directed to preproinsulin were performed with sera from
      patients with recently diagnosed insulin-dependent diabetes mellitus in order to
      localize the antigenic epitopes within the human preproinsulin. Of the patients,
      14% had developed autoantibodies that recognized either the recombinant C-peptide
      or the signal peptide. No reaction was observed with the A-chain or B-chain.

PMID- 7519259
TI  - Selective internal radiation therapy with intra-arterial iodine-131-Lipiodol in
      inoperable hepatocellular carcinoma.
AB  - From August 1990 to June 1993, 26 patients with inoperable hepatocellular
      carcinoma were treated with intra-arterial iodine-131-Lipiodol (131I-L). METHODS:
      Iodine-131-Lipiodol was given through either an implantable arterial port (9
      patients) or during hepatic angiography (17 patients). All 26 patients had
      multiple lesions, 3 had involved resection margin after surgical resection and 1
      had diffuse infiltrative lesions. The median size of the largest tumor among 22
      patients with a measurable lesion was 4.5 cm (2-9.5 cm). The end points are tumor
      response in terms of tumor size, change in serum alpha-fetoprotein level,
      toxicity of treatment and overall survival. RESULTS: Twenty-three patients
      received a single treatment of 1.11-2.22 GBq (30-60 mCi)131I-L. Three patients
      received 2.22-4.44 GBq (60-120 mCi)131I-L in three fractions. Considering both
      radiological regression and reduction in serum alpha-fetoprotein level as
      objective response criteria, the overall response rate was 52% (13 out of 25
      patients with evaluable disease). Ten out of 15 patients who had raised alpha
      fetoprotein levels had more than 50% reduction and 8 patients had more than 90%
      reduction in alpha-fetoprotein level. Since analysis, 19 patients have died and 7
      remain alive, giving a minimum median survival of 6 mo (range 1.2-16.6 mo), with
      4 surviving more than 1 yr calculated from the day of treatment. There was only
      one patient who had late deterioration of liver function compatible with
      radiation hepatitis. There was no bone marrow toxicity documented in any
      patients. CONCLUSION: Treatment with intra-arterial 131I-L was well tolerated in
      patients with inoperable hepatocellular carcinoma and produced an objective
      response of 52% with median survival of 6 mo. A fractionated dose of 131I-L was
      feasible and the radiation dose could be escalated safely.

PMID- 7519261
TI  - Ion permeation properties of the glutamate receptor channel in cultured embryonic
      Drosophila myotubes.
AB  - Ion permeation properties of the glutamate receptor channel in cultured myotubes
      of Drosophila embryos were studied using the inside-out configuration of the
      patch-clamp technique. Lowering the NaCl concentration in the bath (intracellular
      solution), while maintaining that of the external solution constant, caused a
      shift of the reversal potential in the positive direction, thus indicating a
      higher permeability of the channel to Na+ than to Cl- (PCl/PNa < 0.04), and
      suggesting that the channel is cation selective. With 145 mM Na+ on both sides of
      the membrane, the single-channel current-voltage relation was almost linear in
      the voltage range between -80 and +80 mV, the conductance showing some
      variability in the range between 140 and 170 pS. All monovalent alkali cations
      tested, as well as NH4+, permeated the channel effectively. Using the Goldman
      Hodgkin-Katz equation for the reversal potential, the permeability ratios with
      respect to Na+ were estimated to be: 1.32 for K+, 1.18 for NH4+, 1.15 for Rb+,
      1.09 for Cs+, and 0.57 for Li+. Divalent cations, i.e. Mg2+ and Ca2+, in the
      external solution depressed not only the inward but also the outward Na+
      currents, although reversal potential measurements indicated that both ions have
      considerably higher permeabilities than Na+ (PMg/PNa = 2.31; PCa/PNa = 9.55). The
      conductance-activity relation for Na+ was described by a hyperbolic curve. The
      maximal conductance was about 195 pS and the half-saturating activity 45 mM. This
      result suggests that Na+ ions bind to sites in the channel. All data were fitted
      by a model based on the Eyring's reaction rate theory, in which the receptor
      channel is a one-ion pore with three energy barriers and two internal sites.

PMID- 7519265
TI  - Application of dual parameter analysis in flow cytometric DNA measurements of
      paraffin-embedded samples.
AB  - In a comparison of flow cytometric DNA measurements on fresh and paraffin
      embedded material from primary squamous cell carcinomas of the head and neck
      region, we discovered that previously undetected aneuploid clones could be
      detected by dual parameter analysis of cytokeratin and DNA applied to
      disintegrated cells from paraffin sections. Using this new approach the
      correlation coefficient between DNA-indices from fresh and paraffin-embedded
      material increased from 0.423 to 0.904.

PMID- 7519263
TI  - Inhibition of [3H]catecholamine release and Ca2+ currents by prostaglandin E2 in
      rabbit carotid body chemoreceptor cells.
AB  - Basal release of [3H]catecholamine ([3H]CA) from rabbit carotid bodies (CBs),
      previously incubated in the presence of [3H]tyrosine, was not significantly
      modified by prostaglandin E2 (PGE2). On the contrary, PGE2 (3-300 nM) produced a
      dose-dependent inhibition of the low PO2-evoked release of [3H]CA. The inhibition
      was greatest (55%) at a low intensity of hypoxic stimulation (incubating solution
      PO2 approximately 66 mmHg) and decreased with increasing intensities of hypoxia.
      Chronic denervation of the CB did not modify the response to PGE2. The release of
      [3H]CA induced by incubating the CBs in a hypercapnic-acidic solution (PCO2
      approximately 132 mmHg; pH = 6.60) and by dinitrophenol (100 microM) was not
      significantly modified by 300 nM PGE2. PGE2 (300 nM) inhibited the release of
      [3H]CA elicited by incubating the CBs in a high K+ (35 mM)-containing solution.
      The release response elicited by high K+ (25 mM) was strongly augmented by a
      dihydropyridine agonist of Ca2+ channels, Bay K 8644, at a concentration of 1
      microM. The Bay K 8644 effect was partly inhibited by PGE2 (300 nM). Using whole
      cell recordings in freshly dispersed or short-term cultured chemoreceptor cells
      from adult rabbits it was found that Ca2+ currents (ICa) were reversibly
      inhibited by bath application of PGE2. A good parallelism exits between the dose
      response curves for PGE2 inhibition of ICa in isolated chemoreceptor cells and
      high extracellular [K+]- or hypoxia-evoked release of [3H]CA from the whole
      CB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519262
TI  - Rapid down-regulation of substance P binding to guinea-pig pancreatic acinar
      cells during homologous desensitization.
AB  - Binding of 125I-labelled peptides, cytoplasmic Ca2+ concentration ([Ca2+]i) and
      amylase release were studied in guinea-pig pancreatic acinar cells during
      exposure to substance P (SP), and cholecystokinin octapeptide (CCK-8). Pre
      incubation of cells at 22 degrees C with 0.03 nM to 1 microM SP for 10 min or at
      37 degrees C for 5 min followed by acid or neutral washes reduced subsequent
      binding of 125I-Bolton-Hunter reagent-labelled SP (125I-BH-SP) in a biphasic
      manner by up to 95%. Incubation at 4 degrees C eliminated high-affinity binding
      of 125I-BH-SP and concentrations of SP above 1 nM were required for inhibition of
      subsequent tracer binding. Pre-incubation of cells at 37 degrees C with 1 nM to 1
      microM CCK-8 for 10 min followed by neutral washes reduced subsequent binding of
      125I-BH-CCK-8 by up to 65%. In cell suspensions, the [Ca2+]i response to SP was
      gradually reduced by pre-exposure to increasing agonist concentrations from 0.2
      to 20 nM. Pre-incubation with high SP concentrations for 10 min caused profound
      reduction of subsequent amylase responses to SP, whereas secretion was little
      affected in corresponding experiments with CCK-8. Down-regulation of receptor
      binding is not important during short exposure to CCK-8, but it is a pronounced
      and rapid phenomenon during SP exposure, which explains tachyphylaxis of [Ca2+]i
      and amylase responses.

PMID- 7519264
TI  - Changes in cytokeratins following treatment of hamster cheek pouch epithelia with
      hyperplastic or neoplastic agents.
AB  - The effects of four different hyperplastic agents and of the carcinogen DMBA on
      cytokeratin expression in hamster cheek pouch epithelia were compared. Reversible
      hyperplasia was produced by the application of either oil of turpentine, vitamin
      A or TPA. No hyperplastic changes were produced by application of EPP. Apart from
      the transient appearance of a 45 kDa cytokeratin in one group treated with
      vitamin A, the immunohistochemical staining patterns and immunoblot profiles of
      cytokeratins from cheek pouches treated with each of the hyperplastic agents were
      identical to controls. Following application of DMBA, the cytokeratins stained
      with increased intensity in the spinous and granular cell layers. This was
      associated with increased amounts of 42-56 kDa cytokeratins and decreased
      production of 62-75 kDa cytokeratins. Monoclonal antibody AE1 detected a 45 kDa
      cytokeratin in extracts of DMBA-treated epithelia that was not detected in
      untreated epithelial extracts. Monoclonal antibody AE3 detected an additional 54
      kDa cytokeratin band in extracts of DMBA-treated epithelia. These cytokeratin
      changes were present in preneoplastic epithelia and maintained in neoplastic
      epithelia.

PMID- 7519266
TI  - Growth hormone regulates an N-acetylgalactosamine component in odontogenesis: a
      specific lectin-binding study in the Lewis dwarf rat.
AB  - Dental organs of incisors from normal, dwarf and growth hormone-treated dwarf
      rats were analysed histochemically using a panel of lectins. A distinctive
      pattern of differential staining was obtained with Helix pomatia agglutinin, a
      lectin specific for N-acetylgalactosamine. In Bouin's perfused and paraffin
      embedded undecalcified tissues from normal rats, reaction product for N
      acetylgalactosamine was visible in the odontogenic cells and some extracellular
      matrices. In the growth hormone-deficient dwarf rats, the N-acetylgalactosamine
      reaction was consistently minimal in the odontoblasts, predentin, cementoblasts,
      cementoid, osteoblasts and osteoid matrices, although the staining of ameloblasts
      and osteoclasts was similar to normal. Administration of growth hormone to dwarf
      rats for six days (66 micrograms/100 g rat b.i.d.) restored the reaction for N
      acetylgalactosamine in the affected matrices. Thus, an N-acetylgalactosamine rich
      matric component is differentially expressed during odontogensis. Growth hormone
      may regulate this component in these matrices, which may be a proteoglycan or a
      glycoprotein, essential for normal growth of the teeth.

PMID- 7519267
TI  - Immunocytochemical localization of bone morphogenetic proteins (BMPs) in salivary
      gland pleomorphic adenoma.
AB  - The localization of bone morphogenetic protein (BMP)-1, -2, -3 and transforming
      growth factor (TGF)-beta in normal salivary gland and pleomorphic adenoma of the
      salivary gland has been examined immunocytochemically. Tumor cells with BMP
      immunostaining in pleomorphic adenoma were associated with some solid cellular
      and tubuloglandular patterns, and with stellate cells in the myxoid area. In
      addition, in the chondroid area of three pleomorphic adenomas, chondrocyte-like
      cells were positive for BMPs. It is speculated that BMPs secreted by the tumor
      cells play a role in the formation of the chondroid component in pleomorphic
      adenoma by inducing some tumor cells, probably neoplastic myoepithelial cells, to
      differentiate to chondrocytes by metaplastic change. No tumor cells specifically
      immunostained with TGF-beta were found. TGF-beta was positive in fibrous and
      hyalinized stroma. In the submandibular gland, only anti-BMP-1 antibody
      specifically reacted to apical portions of degenerated serous acinar cells.

PMID- 7519268
TI  - Pathological and therapeutic implications for nitric oxide in inflammatory bowel
      disease.

PMID- 7519270
TI  - K1, K5 and O antigens of Escherichia coli in relation to serum killing via the
      classical and alternative complement pathways.
AB  - The sensitivity of Escherichia coli strains to 80% normal human serum (NHS) and
      the relative importance of the classical and alternative complement pathways was
      assessed in relation to K1, K5, and O antigen carriage. Strains of each of the
      common O-serogroups, O1, O2, O4, O6, O7, O9, O18 and O75, smooth strains not
      typable (NT) with these antisera and auto-agglutinable (AA) strains were studied.
      Of the 166 strains studied, 37 carried the K1 antigen and 45 the K5 antigen. The
      variation in sensitivity to NHS between different O-serogroups reported
      previously was confirmed. Although carriage of the K1 and K5 antigens varied with
      O-serogroup, this did not explain the differences either between or within O
      serogroups. Strains with the K1 or K5 antigen were significantly more resistant
      to the alternative complement pathway than strains without these antigens.
      However, this appeared to be more related to the O-serogroups with which they
      were associated; 37 of 50 O2, O4, O6 and AA strains were affected by complement
      through both pathways but 20 of 30 O7, O18 and O75 strains were affected by the
      classical pathway alone and 16 of 20 O9 and NT strains were affected by the
      alternative pathway alone.

PMID- 7519269
TI  - Application of pyrolysis mass spectroscopy and SDS-PAGE in the study of the
      epidemiology of Pseudomonas cepacia in cystic fibrosis.
AB  - Representative isolates of Pseudomonas cepacia from 15 cystic fibrosis (CF)
      patients attending the Respiratory Unit of Alder Hey Childrens' Hospital were
      investigated by SDS-PAGE of whole-cell polypeptides and by pyrolysis mass
      spectroscopy (PMS). SDS-PAGE was less discriminatory than PMS. Eleven isolates
      were indistinguishable by PMS and considered to represent re-isolates of an
      endemic strain; four isolates were distinct from this group, and from one
      another. P. cepacia was first isolated on the unit in July 1989 from a patient
      who had attended a UK selection meeting for a Canadian CF camp. A ward and
      outpatient segregation policy was introduced, but colonisation of further
      patients occurred. In August 1991, the Adult CF Association recommended that all
      social activities involving colonised patients should cease. This, and an
      increased awareness amongst older CF patients of the risks of person-to-person
      transmission, was associated with a marked decline in new cases. Social activity
      and hospital admissions were compared for colonised patients during the year
      before colonisation with P. cepacia, and matched patients who did not acquire the
      endemic strain. This showed a significantly higher attendance at CF social events
      for colonised patients, but no significant association between colonisation and
      hospital admission. These results are strong indirect evidence that transmission
      of P. cepacia occurs through social contact outside the hospital environment.

PMID- 7519271
TI  - Regulation of the transcription of a cluster of Bacillus subtilis spore coat
      genes.
AB  - The pattern of transcription has been examined for a cluster of genes encoding
      polypeptides some or all of which are assembled into a cross-linked component of
      the Bacillus subtilis spore coat. Three promoters, designated PVWX, PX and PYZ,
      were indicated by reverse transcriptase mapping. On the basis of Northern
      hybridization, it appeared that the cotV, W and X genes were transcribed as a
      polycistronic mRNA from PVWX as well as a monocistronic cotX mRNA from Px. The
      cotY and cotZ genes are cotranscribed from the PYZ promoter with a smaller cotY
      mRNA resulting from premature termination or RNA processing. All four transcripts
      were synthesized late during sporulation and were not produced in mutants lacking
      sigma K, which directs RNA polymerase to transcribe genes in the mother-cell
      compartment of sporulating cells. The DNA-binding protein GerE, which affects
      transcription of many genes in the mother cell during the late stages of
      sporulation, was also shown to be involved. There was essentially no cotX mRNA in
      a gerE mutant and the amounts of cotVWX, cotYZ and cotY mRNAs were somewhat
      reduced. In vitro run-off transcription studies with sigma K RNA polymerase and
      GerE confirmed the presence of the three promoters, and directly showed that GerE
      was necessary for transcription from PX as well as enhanced transcription from
      the PVWX and PYZ promoters. The DNase I footprints of GerE for all three
      promoters were immediately upstream of the -35 regions. These GerE binding sites
      were compared to those in other GerE-responsive promoters and a larger consensus
      sequence for GerE binding was recognized. This complex transcriptional pattern of
      the cotVWXYZ cluster is probably necessary to ensure that an optimal amount of
      each protein is made for the assembly of the spore coat.

PMID- 7519272
TI  - Human interleukin 1 beta: corticotropin releasing factor and ACTH release and
      gene expression in the male rat: in vivo and in vitro studies.
AB  - Numerous studies have shown that interleukin 1 (IL1), a cytokine secreted by
      macrophages, is capable of stimulating the hypothalamo-pituitary-adrenal (HPA)
      axis. Nevertheless, the sites involved in IL1 stimulation of the HPA axis remain,
      to date, subjects of controversy. In the present study, using in vivo and in
      vitro approaches, we tried to characterize the route by which IL1 acts on the HPA
      axis. In vivo, after an i.p. injection of human IL1 beta (1 microgram/rat), we
      measured plasma ACTH concentration, anterior pituitary (AP) ACTH content,
      hypothalamic (HT) corticotropin releasing factor (CRF) content, and also AP pro
      opiomelanocortin (POMC) and HT CRF gene expression. ACTH and CRF were measured by
      specific radioimmunoassays (RIAs), and solution hybridization nuclease protection
      assay was used for quantification of nuclear POMC precursor RNA and nuclear and
      cytoplasmic POMC and CRF mRNA. Human IL1 beta provoked an increase in ACTH plasma
      concentration, a decrease in AP ACTH content, and a prolonged increase in AP POMC
      primary transcript levels (around 100%). A significant increase in AP POMC
      primary transcript content was evident 30 min after injection of hIL1 beta, while
      cytoplasmic POMC mRNA levels were increased in the AP only at 4 hr after
      injection of hIL1 beta. We did not observe an effect of hIL1 beta on either HT
      CRF content or HT CRF cytoplasmic mRNA levels. In order to characterize a
      possible direct effect of hIL1 beta at the AP level, we used an AP perifusion
      system to analyse the effect of hIL1 beta and CRH on ACTH release and on POMC
      gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519275
TI  - Histology of lipoid proteinosis.

PMID- 7519274
TI  - Molecular cloning and expression of a delta-opioid receptor from rat brain.
AB  - We have isolated and characterized a rat delta-opioid receptor. The deduced amino
      acid sequence (372 aa) closely resembles the murine delta-opioid receptor, DOR-1.
      In fact, 97% of the amino acid residues are conserved between the two species,
      while 93% of the nucleic acid residues are identical. A 6 kb mRNA was detected in
      rat cortex using rat DOR-1 as a probe. When expressed in COS cells, the clone
      shows high-affinity opioid binding with selectivity for delta-opioids. The rat
      delta-opioid receptor cDNA clone will be a useful tool for studying the function
      of delta-opioid receptor in rats.

PMID- 7519273
TI  - Transcriptional regulation of myelin associated glycoprotein gene expression by
      cyclic AMP.
AB  - The treatment of rat glioma C6 cells with 10 microM isoproterenol (Ipt) for 4
      days upregulated the expression of the myelin-associated glycoprotein (MAG) gene
      by approximately 55-fold over the control value. The constant presence of Ipt in
      the medium was required for the maximal upregulation, as time-restricted
      exposures to the drug produced only partial, or no upregulation of the gene. No
      difference in the MAG mRNA stability could be detected in Ipt-treated vs
      untreated cells indicating that the drug upregulates the MAG gene at
      transcriptional level. Serum (FCS) strongly attenuated the response of the MAG
      gene to Ipt. The stimulatory effect of Ipt was profoundly reduced by spermine and
      H-89, indicating that protein kinase A-dependent protein phosphorylation is
      involved in the MAG gene activation. Within 30 min after Ipt administration, the
      c-fos gene was upregulated by 10-fold, and thereafter, its message level
      decreased and stabilized at approximately 3-fold over control. In contrast, the c
      jun gene was downregulated to approximately 20% of control within 30 min after
      Ipt administration. Subsequently, its message level rose and fell once again
      within 12 h to approximately half of control, and returned to control level
      within 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519277
TI  - [Hemostasis techniques in transvesical excision of a prostatic adenoma].
AB  - A technique for hemostasis in performance of transcystic adenomectomy by means of
      the four U-like removable catgut ligatures has been suggested. Two hundred and
      sixty-three transcystic adenomectomies were performed. Early postoperative
      bleeding was noted in 1 (0.4%) patient, the late one--in 2 ((0.8%). The average
      duration postoperative hospitalization was 18.8 days.

PMID- 7519276
TI  - [Region-specified PCR-mutagenesis: its application to locate epitopes for anti
      RecA protein-monoclonal IgGs ].
AB  - Even though various techniques for site-directed mutagenesis have been developed,
      random mutagenesis is an important and complementary approach to locate
      functional domains on polypeptides and RNA, and to modify their biochemical and
      biological properties. Region-specified PCR-mutagenesis is a powerful and simple
      technique for this purpose. A couple of primers specifies a DNA region to be
      mutagenized. By use of Taq DNA polymerase and the addition of deoxyinosine
      triphosphate (dITP), PCR causes various base-substitutions in the region. By
      screening of a change in a phenotype of the protein, one can obtain mutants with
      significant phenotype at 10(-2) from an expressed library of mutagenized DNA.

PMID- 7519279
TI  - Affinity extraction with dye ligands.

PMID- 7519278
TI  - Magnetically enhanced phase separation.

PMID- 7519280
TI  - Purification of lactate dehydrogenase from pig muscle by affinity partitioning.

PMID- 7519282
TI  - Partitioning of blood proteins using immobilized dyes.

PMID- 7519283
TI  - Separation of proteins and nucleic acids.

PMID- 7519281
TI  - Phosphofructokinase from baker's yeast.

PMID- 7519285
TI  - Protein-protein and protein-ligand interactions.

PMID- 7519284
TI  - Cross-partitioning: determination of isoelectric point by partitioning.

PMID- 7519287
TI  - Analysis of structural changes in steroid receptor proteins by partitioning.

PMID- 7519286
TI  - Detection of conformational changes in proteins by probing with poly(ethylene
      glycol)-bound ligands.

PMID- 7519288
TI  - Analytical applications of partitioning: detection of differences or changes in
      surface properties of mammalian cell populations.

PMID- 7519289
TI  - Cell-cell affinity.

PMID- 7519290
TI  - Testing for charge and hydrophobicity correlates in cell-cell adhesion.

PMID- 7519291
TI  - Classification of Penicillium fungi by cross-partition analysis.

PMID- 7519292
TI  - Charge-directed affinity partitioning of cells.

PMID- 7519293
TI  - Factors in the affinity extraction of red blood cells using poly(ethylene glycol)
      metal chelate.

PMID- 7519294
TI  - Use of polyacrylamide-derivatized antibody in dextran-poly(ethylene glycol)
      systems.

PMID- 7519295
TI  - Bioextraction of low abundance cells by affinity partitioning.

PMID- 7519296
TI  - Preparation of synaptosomes and mitochondria from mammalian brain.

PMID- 7519297
TI  - Partitioning procedures and techniques: cells, organelles, and membranes.

PMID- 7519298
TI  - Plasma and internal membranes from cultured mammalian cells.

PMID- 7519299
TI  - Rat liver plasma membranes.

PMID- 7519300
TI  - Relative proximity of domains in plasma membrane and smooth endoplasmic reticulum
      from rat liver.

PMID- 7519301
TI  - Biotransformation of hydrocortisone into prednisolone.

PMID- 7519303
TI  - Isolation and characterization of two IgE-reactive proteins from Azadirachta
      indica pollen.
AB  - Two allergenically active components present in the Azadirachta indica whole
      pollen extract have been isolated by sequential ammonium sulfate precipitation (0
      90%), DEAE-Sephadex A-50 ion-exchange chromatography followed by gel filtration
      through Sephadex G-200. The allergenicity of fractionated materials has been
      tested by skin prick test and ELISA inhibition which reveal that AIaI and AIaIVb
      are the major allergens. Immunoblot confirms the IgE-binding activity of the
      proteins. Although both fractions are found to be homogeneous by SDS-PAGE,
      isoelectric focusing produces more than one isoelectric point in AIaI (pI = 3.15,
      3.3 and 3.5) and AIaIVb (pI = 6.0 and 6.2). Amino acid analyses of the two
      allergens, the effect of pH on them and cross-reactivity between them have been
      discussed.

PMID- 7519306
TI  - Micronucleated erythrocytes as an assay to assess actions by physical and
      chemical genotoxic agents in Clarias gariepinus.
AB  - An in vivo study on the effects of both physical (gamma-radiation) and chemical
      (mitomycin C) genotoxic agents was carried out with the catfish species, Clarias
      gariepinus. The fish were either exposed to gamma-radiation at doses of 0-9 Gy or
      injected intraperitoneally with mitomycin C at concentrations of 0-2 mg/kg.
      Micronucleated erythrocytes were sampled from 0 to 60 days post treatment. Data
      obtained showed a time-dependent response of the induction of micronucleated
      erythrocytes with both genotoxic agents. A linear dose-dependent increase was
      observed 2-4 days after treatment. These data show the importance of sampling
      time in the micronucleus assay with Clarias gariepinus.

PMID- 7519304
TI  - T cell epitope recognition involved in the low-responsiveness to a region of hen
      egg lysozyme (46-61) in C57BL/6 mice.
AB  - The predominant T cell epitope of hen egg lysozyme (HEL) in high-responder C3H
      mice has been previously identified as the HEL 46-61 region. In contrast, this
      region is poorly recognized by T cells from low-responder C57BL/6 mice upon
      immunization with HEL. In previous studies, we have demonstrated that several
      C57BL/6 derived T cell hybridomas reactive to this epitope and other HEL epitopes
      preferentially recognize phosphorylcholine (PC)-conjugated HEL over unconjugated
      HEL. To understand the mechanisms involved in this difference of T cell
      recognition, we have further analysed the reactivity of T cells and T cell
      hybridomas from low-responder C57BL/6 mice. T cells from HEL-immunized mice were
      preferentially reactive to HEL 47-60. These results suggest a potential
      deficiency in generating an appropriate T cell epitope from the 46-61 region of
      native HEL in low-responder C57BL/6 mice. The minimal T cell epitope of this
      region was defined as HEL 51-60 using the PCH4.1 T hybridoma clone. This minimal
      epitope represents a single amino acid shift from the minimal epitope of HEL high
      responder C3H mice (HEL 52-61). Various peptides representing this region were
      synthesized with single alanine substitutions at each position. The residues at
      positions 51, 52, 53 and 57 of HEL appear to be involved in Ia binding and the
      residues at 55 and 56 in contracting the TCR. T cell reactivity to HEL 51-61
      peptides with various substitutions at position 61 strongly suggest that
      primarily the size of the C-terminal residue interferes with binding to the Ia
      molecules of low-responder mice. In addition, substitutions of the TCR contacting
      residues at positions 55 and 56 with similar residues (isoleucine-->leucine or
      leucine-->isoleucine) significantly increased the T cell reactivity, suggesting a
      low reactivity with the native residues. Therefore, the requirement of many
      residues in the T cell epitope for interaction with Ia, the necessity for
      additional Ag processing to facilitate Ia binding, and the low affinity of the
      TCR contacting residues may together render C57BL/6 mice unresponsive to the HE
      46-61 region.

PMID- 7519307
TI  - Sister-chromatid exchanges in epileptic patients on anticonvulsant therapy.
AB  - Sister-chromatid exchanges (SCE) have been studied to analyze genotoxic effects
      in epileptic patients on anticonvulsant therapy. All patients had an increased
      frequency of SCE per metaphase (p < 0.001) compared to controls, indicating a
      genotoxic effect of anticonvulsant drugs.

PMID- 7519305
TI  - Profile of the regions of acetylcholine receptor alpha chain recognized by T
      lymphocytes and by antibodies in EAMG-susceptible and non-susceptible mouse
      strains after different periods of immunization with the receptor.
AB  - C57BL/6 (B6) mice develop a neuromuscular disease, experimental autoimmune
      myasthenia gravis (EAMG), after two or more immunizations with Torpedo
      californica acetylcholine receptor (AChR). To determine whether EAMG is related
      to recognition of particular region(s) on the main extracellular domain of the
      alpha chain (residues alpha 1-210) in prolonged immunization, we have examined
      the differences in the antibody and T cell recognition profiles of B6 and SJL (a
      strain that does not develop EAMG) mice after different periods and a number of
      immunizations with Torpedo AChR. In a given strain, antibodies and T cells
      recognized immunodominant regions, which may coincide or may be uniquely B cell
      or T cell determinants. Both B6 and SJL exhibited similar antibody recognition
      profiles after the second and through the fourth immunizations with AChR. Major
      differences between the two strains were found in their T cell recognition of
      regions in the second part (residues 100-210) of the main extracellular domain of
      the alpha chain. T cells of SJL recognized consistently only one region (111-126)
      within this part of the alpha chain, whereas in B6, T cell recognition of three
      peptides (111-126, 146-162 and 182-198) and next neighbor regions to them
      persisted throughout the period. Of these three peptides, 146-162 was an
      immunodominant peptide unique to B6, as the other two peptides (111-126 and 182
      198) were also recognized by either T cells or antibodies in SJL. To study the
      role of the T cells recognizing region 146-162 in EAMG, a T cell line was
      generated against this region and the cells transferred into B6 mice followed by
      one Torpedo AChR injection. Enhancement of antibody production toward alpha chain
      peptides was observed as an influence of T cell transfer compared to profiles at
      1 week. In addition, one out of three mice examined showed signs of EAMG. These
      results suggest the importance of T cells recognizing residues 146-162 in EAMG.
      It is concluded that the presence of persistent T cell responses to the second
      half (residues (100-210) of the main extracellular domain of the alpha chain is
      associated with the development of EAMG in B6 mice, while absence of these
      responses in SJL mice may enable them to escape the disease. The preservation of
      the immunodominance of peptide 146-162 in the T cell recognition of B6 is
      probably most important for the pathogenesis of EAMG in this strain.

PMID- 7519302
TI  - Purification of water-based cutting fluids.

PMID- 7519309
TI  - DNA breakage by tannic acid and Cu(II): sequence specificity of the reaction and
      involvement of active oxygen species.
AB  - Tannic acid has numerous chemical, food and pharmacological applications. In the
      presence of Cu(II) and molecular oxygen it was found to cause breakage of calf
      thymus DNA and supercoiled plasmid DNA. Treatment of lambda phage DNA with tannic
      acid protected cleavage with restriction endonucleases DraI and EcoRI* but not
      with SmaI and HaeIII. The results indicate that under the conditions used tannic
      acid preferably binds to AT base pairs. Restriction analysis of open circular
      form II plasmid DNA generated by tannic acid-Cu(II) treatment further showed that
      the strand breakage is caused at specific sites or sequences. In this reaction
      Cu(I) was shown to be an essential intermediate by using the Cu(I) sequestering
      reagents neocuproine and bathocuproine. By using job plots, we established that
      in the absence of DNA, six Cu(II) ions can be reduced by one tannic acid
      molecule. The involvement of active oxygen species in the reaction was
      established by the inhibition of DNA breakage by superoxide dismutase, thiourea,
      mannitol, formate and catalase.

PMID- 7519308
TI  - Quantitative carcinogenesis and dosimetry in rainbow trout for aflatoxin B1 and
      aflatoxicol, two aflatoxins that form the same DNA adduct.
AB  - Two exposure protocols were used to establish complete dose-response
      relationships for the hepatic carcinogenicity and DNA adduction in vivo of
      aflatoxin B1 (AFB1) and aflatoxicol (AFL) in rainbow trout. By passive egg
      exposure, AFL was taken up less well than AFB1, but was more efficiently
      sequestered into the embryo itself, to produce an embryonic DNA binding curve
      that was linear with carcinogen dose and with a DNA binding index three-fold
      greater than AFB1. Both aflatoxins produced the same phenotypic response,
      predominantly mixed hepatocellular/cholangiocellular carcinoma. Tumor responses
      as logit [incidence] vs. In [dose] were parallel-offset, non-linear responses
      showing a three-fold greater carcinogenic potency for AFL at all doses examined
      (i.e. 3 times more AFB1 than AFL required to produce an equivalent liver tumor
      incidence). By molecular dosimetry analysis (logit [incidence] vs. In [DNA
      adducts]), the two data sets were coincident, indicating that, per DNA adduct
      formed in vivo in total embryonic DNA, these two aflatoxins were equally
      efficient in tumor initiation. By dietary fry exposure, both carcinogens produced
      linear DNA binding dose responses in liver, but with an AFL target organ DNA
      binding index only 1.14 times that of AFB1 by this exposure route. The tumor dose
      response curves also did not exhibit the three-fold difference shown by embryo
      exposure, but were closely positioned non-linear curves. Since the DNA binding
      indices differed by only 14%, the resulting molecular dosimetry curves for AFL
      and AFB1 by dietary exposure were similar to the tumor response curves. These
      results indicate that differing exposure routes produced differing relative
      carcinogenicity estimates based on doses applied, as a result of protocol
      dependent differences in AFL and AFB1 pharmacokinetic behaviors, but that potency
      comparisons based on molecular dose received were similar for the two protocols.
      By comparison with standard DNA adducts produced in vitro using the
      dimethyloxirane-produced 8,9-epoxides of AFB1 and AFL, we conclude that > 99% of
      AFL-DNA adducts produced in vivo were identical to those produced by AFB1. Thus
      similar molecular dosimetry responses should be expected under all exposure
      protocols in which the two parent carcinogens do not exhibit differing toxicities
      to the target organ.

PMID- 7519310
TI  - DNA breakage by tannic acid and Cu(II): generation of active oxygen species and
      biological activity of the reaction.
AB  - Tannic acid was shown to reduce oxygen to superoxide anion. In the presence of
      Cu(II), the hydroxyl radical and hydrogen peroxide were formed. Strand scission
      reaction was shown to account for the biological activity of tannic acid as
      assayed by bacteriophage inactivation. The inactivating activity occurs through
      the Fenton pathway for free radical production and subsequent DNA cleavage by
      these radicals.

PMID- 7519311
TI  - Human micronucleus counts are correlated with age, smoking, and cesium-137 dose
      in the Goiania (Brazil) radiological accident.
AB  - A random sample of 276 people representing control, direct exposure, and probable
      indirect exposure in the Goiania, Brazil radiological accident was examined using
      micronuclei as indicators of cytogenetic damage. The Goiania subjects were
      analyzed for interactions of age, lifestyle, and ionizing radiation dose.
      Increases in micronucleus frequencies were most strongly correlated with the dose
      of ionizing radiation, but age, alcohol consumption, and smoking habits also
      affected micronucleus frequencies. Despite these additional influences,
      micronucleus frequencies can be useful as biological dosimeters.

PMID- 7519312
TI  - Multiple regression analysis of cytogenetic human data.
AB  - Biomonitoring studies on cytogenetic outcomes in humans should be considered as
      epidemiological studies, rather than randomized trials. Under this light the
      emphasis given to the achievement of a significant p-value should be reduced,
      since this measure suffers from major limitations. The use of a point estimate
      (and its corresponding confidence interval) to measure the association between
      exposure and effect offers several advantages, including the adjustment for
      confounding, and the evaluation of possible interaction between factors. In most
      instances the use of multivariate statistical methods allows an efficient
      analysis of these studies, even in presence of a small sample size and several
      covariates. In this paper we re-analyzed four biomonitoring studies by using
      multivariate methods to estimate relative risks through statistical modeling. The
      use of multiple regression techniques allowed the computation of point estimates
      of association and their confidence intervals for each covariate evaluated by the
      studies considered; the estimate of the effect of confounding variables such as
      smoking habits, age and gender; and the presence of interaction between
      covariates. Measures of association estimated through univariate and multivariate
      statistical approaches are compared. The advantages of the latter technique are
      discussed.

PMID- 7519314
TI  - Induction of binucleation in human lymphocytes by 14 synthetic isoindolone
      derivatives related to cytochalasins.
AB  - Fourteen hydrogenated isoindolone derivatives with affinity to cytochalasin B
      were synthesized and tested for the induction of binucleation in the human
      lymphocyte micronucleus (MN) assay. The experimental procedure was the one
      commonly used for the human lymphocyte MN assay. Compounds like cyt-B were added
      to cultures at 44 h and tested at increasing concentrations, up to 200 mumol/l,
      in the range commonly used for cyt-B in the MN assay (3 micrograms/ml = 6.25
      mumol/l). Induction of cytokinesis-blocked binucleated cells was found for all
      compounds but, at the same molarity, cyt-B induced a higher percentage of
      binucleation. Only one of the compounds tested was found to induce micronuclei
      significantly: MN were induced across the dose range of 25-100 mumol/l.

PMID- 7519313
TI  - Comparison of common gene mutation tests in mammalian cells in culture: a
      position paper of the GUM Commission for the Development of Guidelines for
      Genotoxicity Testing.
AB  - In gene mutation tests a decision concerning mutations is made on the basis of
      hereditary functional changes. In terms of the large amount of data available,
      the most suitable tests for routine testing in mammalian cells in culture are the
      tests for acquisition of 6-thioguanine resistance in Chinese hamster cells (V79
      and CHO) and for acquisition of alpha,alpha,alpha-trifluorothymidine resistance
      in the mouse lymphoma line L5178Y TK+/- 3.7.2C. The molecular bases,
      peculiarities, advantages and disadvantages of these systems will be presented.
      Which system is to be preferred in any particular case depends among other things
      on the purpose of the study and the extent to which a technically competent
      performance of these comparatively exacting tests can be guaranteed.

PMID- 7519315
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Deoxyribonucleoside triphosphate levels: a critical factor in the
      maintenance of genetic stability.
AB  - DNA precursor pool imbalances can elicit a variety of genetic effects and
      modulate the genotoxicity of certain DNA-damaging agents. These and other
      observations indicate that the control of DNA precursor concentrations is
      essential for the maintenance of genetic stability, and suggest that factors
      which offset this control may contribute to environmental mutagenesis and
      carcinogenesis. In this article, we review the biochemical and genetic mechanisms
      responsible for regulating the production and relative amounts of intracellular
      DNA precursors, describe the many outcomes of perturbations in DNA precursor
      levels, and discuss implications of such imbalances for sensitivity to DNA
      damaging agents, population monitoring, and human diseases.

PMID- 7519316
TI  - Modulating influence of inorganic arsenic on the recombinogenic and mutagenic
      action of ionizing radiation and alkylating agents in Drosophila melanogaster.
AB  - In bacterial systems and in mammalian in vitro cell cultures, inorganic arsenic
      has been found to potentiate the mutagenic action of UV as well as of a number of
      mutagenic agents, probably by interfering with the later steps of DNA-repair. The
      Drosophila wing spot test (SMART) was used to study the modulating action of
      inorganic arsenic on the recombinogenic and mutagenic effects of the alkylating
      agents ethylnitrosourea (ENU), methylmethane sulphonate (MMS), and ethylene oxide
      (EO) as well as of gamma-rays. It was found, that arsenic in this in vivo test
      system exerted an inhibitory effect on mitotic recombination induced by
      alkylating agents and gamma-irradiation. These results are in contrast to the
      synergistic effect of inorganic arsenic on point mutations and deletions as
      reported for human lymphocytes and primary fibroblasts. The reason for the
      discrepancy between the mammalian systems and Drosophila with respect to the
      modulating action of arsenic is discussed.

PMID- 7519317
TI  - Chloral hydrate is recombinogenic in the wing spot test in Drosophila
      melanogaster.
AB  - In order to characterise the response of the wing spot test in Drosophila
      melanogaster to the effects of compounds with known aneugenic properties,
      experiments were performed with chloral hydrate (CH). Following chronic exposure
      of 72-h-old larvae to rising concentrations of CH, significant increases in the
      frequency of small (1-2 cells) single spots were observed. Comparison of results
      obtained in parallel from the wings of marker-trans-heterozygous individuals and
      individuals heterozygous for one of two different balancer chromosomes suggests
      that practically all the single clones originated from recombinational events.
      Twin clone frequencies were, however, only weakly affected. These results are
      discussed with reference to the literature regarding the effects of CH in
      different experimental systems and to the characteristics of Drosophila as a
      tester organism.

PMID- 7519318
TI  - Dose dependence of radiation-induced micronuclei in cytokinesis-blocked human
      lymphocytes.
AB  - Following selection of appropriate culture conditions, various experiments were
      conducted to evaluate the suitability of the micronucleus assay in cytokinesis
      blocked lymphocytes for biological dosimetry purposes. A dose-effect relationship
      was determined, based on the frequency of micronuclei induced by various doses of
      60Co gamma-rays. The data were best fitted to a linear-quadratic model. To
      validate the system, an attempt was made to estimate unknown dose levels from the
      yield of micronuclei, by inverting the derived dose-response function. It was
      concluded that the assay provides a valid approach for dose assessment. The size
      of radiation-induced micronuclei was measured in relation to the dose. A
      significant difference in the proportion of large micronuclei between high and
      low doses was observed. The chromosomal composition of micronuclei, detected by
      immunofluorescent staining of kinetochores, showed that only a small proportion
      of micronuclei contains kinetochore. The possible contribution of various
      mechanisms for the formation of large radiation-induced micronuclei is discussed.

PMID- 7519319
TI  - Induction of gene mutation in mammalian cells by 3-chloro-4-(dichloromethyl)-5
      hydroxy-2(5H)-furanone (MX), a chlorine disinfection by-product in drinking
      water.
AB  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent direct-acting
      Salmonella mutagen found in chlorinated drinking water, was tested in Chinese
      hamster ovary (CHO) cells for the induction of mutation at the hypoxanthine
      phosphoribosyl transferase locus to 6-thioguanine resistance (TGr). MX treatment
      of CHO cells for 3 h at 37 degrees C resulted in significant dose-related
      increases in mutant frequency. The lowest observed effective dose was 2.5
      micrograms/ml, where the cloning efficiency estimated on the day after treatment
      was not affected. The relationship between the dose of MX and the frequency of
      TGr mutants was approximately linear over the range of 0-5 micrograms/ml with an
      estimated slope (+/- 95% confidence limits) of 7.2 +/- 2.6 mutants per 10(6)
      clonable cells per microgram/ml.

PMID- 7519320
TI  - Bacterial mutagenicity of eight medicinal herbs from Zimbabwe.
AB  - Eight plants traditionally used as medicines in Zimbabwe were evaluated for
      mutagenicity. The required plant parts were dried, powdered and extracted in a
      Soxhlet apparatus with distilled water. The extracts were tested using Salmonella
      typhimurium strains TA97a, TA98, TA100 and TA102. The results indicate five of
      these extracts are nonmutagenic in the assay while three of the extracts were
      found to be mutagenic. The three plant extracts, namely those of Combretum
      erythrophyllum, Gnidia kraussiana and Barlerii randii, were found to be mutagenic
      to strain TA102. Furthermore, the extract of C. erythrophyllum was also mutagenic
      to strain TA100. The presence of S9 mix appeared to diminish the mutagenicity of
      the extracts except in the case of C. erythrophyllum, the mutagenicity of which
      was enhanced in strain TA100. These results assume importance in view of the fact
      that these plants are used as therapeutic agents.

PMID- 7519321
TI  - The genotoxicity of 1,4-dioxane.

PMID- 7519322
TI  - Activity of the rodent carcinogen 1,4-dioxane in the mouse bone marrow
      micronucleus assay.

PMID- 7519324
TI  - Activity of 1,4-dioxane in mouse bone marrow micronucleus assays.

PMID- 7519325
TI  - The genotoxicity of Hinosan, an organophosphorus pesticide in the in vivo mouse.
AB  - The genotoxic potential of Edifenphos (Hinosan) was studied in the in vivo mouse
      system. The test parameters used were chromosomal aberration assay, micronucleus
      test and sperm abnormality assay. The dose and time yield effects of the
      pesticide were investigated for chromosomal aberrations and the micronucleus
      test. Statistically significant chromosomal aberrations, micronucleus and sperm
      abnormalities revealed the genotoxicity of this compound.

PMID- 7519323
TI  - Results of mouse bone marrow micronucleus studies on 1,4-dioxane.

PMID- 7519326
TI  - Inhalation studies of the genotoxicity of trichloroethylene to rodents.
AB  - Trichloroethylene (TCE) (CAS No. 79-01-6) is an industrial solvent used in
      degreasing, dry cleaning, and numerous other medical and industrial processes.
      Controlled inhalation studies were performed using male C57BL/6 mice and CD rats
      to determine if TCE can induce cytogenetic damage in vivo. Animals were exposed
      in groups of five to target concentrations of either 0, 5, 500, or 5000 ppm TCE
      for 6 h. Tissue samples were taken between 18 and 19 h post exposure. Peripheral
      blood lymphocytes (PBLs) in rats and splenocytes in mice were cultured and
      analyzed for the induction of sister-chromatid exchanges, chromosome aberrations,
      and micronuclei (MN) in cytochalasin B-blocked binucleated cells. Bone marrow
      polychromatic erythrocytes (PCEs) were analyzed for MN. The only positive
      response observed was for MN in rat bone marrow PCEs. TCE caused a statistically
      significant increase in MN at all concentrations, inducing an approximate
      fourfold increase over control levels at 5000 ppm. TCE was also cytotoxic in
      rats, causing a significant concentration-related decrease in the ratio of
      PCEs/normochromatic erythrocytes. This study indicates that there may be species
      specific cytogenetic effects attributed to TCE inhalation exposure. In follow-up
      studies, CD rats were exposed for 6 h/day over 4 consecutive days to either 0, 5,
      50 or 500 ppm TCE. No statistically significant concentration-related increases
      in cytogenetic damage were observed. While the MN frequencies in the 4-day study
      were comparable to those at the equivalent concentrations in the 1-day study,
      they were not significantly elevated due to an unusually high MN frequency in the
      controls. A subsequent replication of the 1-day 5000 ppm TCE exposure with rats
      again showed a highly significant increase in MN frequencies compared to
      concurrent controls.

PMID- 7519327
TI  - Screening for agents inhibiting the mutagenicity of extracts and constituents of
      tobacco products.
AB  - The aim of this study was to screen for potential agents affecting the
      mutagenicity of tobacco products. The influence of a number of compounds which
      have been suggested to be antimutagenic some of which are present in tobacco
      products, was investigated on the mutagenicity of a cigarette smoke condensate
      (CSC) and, in some cases, an extract of oral Swedish moist snuff (SNUS), using a
      screening procedure of the Ames Salmonella/microsome assay (STY). For some of the
      compounds the V79/hprt mutagenicity assay with benzo[a]pyrene metabolites as
      mutagens was used to obtain complementary and confirmatory information on
      mammalian cells. The antimutagens used included two selenium compounds, sodium
      selenite and ebselen; the flavonoids and polyphenols, ellagic acid, (+)-catechin
      hydrate, scopoletin, chlorogenic acid and rutin trihydrate; the porphyrin
      derivatives, bovine hemin, biliverdine dihydrochloride, chlorophyllin and a plant
      extract containing chlorophyll; the terpenoids, beta-carotene, retinol and a
      mixture of the two epimers (4R) and (4S) of (1S,2E,6R,7E,11E)-cembra-2,7,11
      triene-4,6-diols (CBD); and cyclohexanol and ubiquinone. Screening of
      antimutagenic activities using the STY involves problems with toxicity. In
      several cases in this study mutagenicity was decreased below the control level
      without signs of toxicity in the background growth of bacteria. Since the
      survival of mutants and slight bacteriostatic effects on the background growth
      cannot be determined accurately in the STY, a reduction in mutagenicity may
      simply be due to toxicity. Only in cases where a dose-response curve declines to
      a level at or above the background and then levels off, can toxicity be excluded.
      An antimutagenic effect determined using this test system is therefore often not
      sufficient for classifying a compound as antimutagenic until these findings are
      confirmed in other test systems and, preferably, the mechanism behind this effect
      is clarified. The results obtained with the selenium compounds were considered to
      be inconclusive since the reduction in the mutation rate declined below the
      background level and might only reflect the toxic effects of these compounds. For
      ellagic acid an almost complete inhibition of the mutagenicity of CSC and SNUS in
      STY was indicated. This indication of antimutagenicity was confirmed in V79 cells
      using two metabolites of the CSC constituent benzo[a]pyrene, i.e., trans-7,8
      dihydroxy-7,8-dihydrobenzo[a]pyrene and (+)-7 beta, 8 alpha-dihydroxy-9 alpha, 10
      alpha-oxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE). Chlorogenic acid and (+)-
      catechin reduced the mutagenicity of CSC and chlorogenic acid also strongly
      inhibited SNUS mutagenicity. Scopoletin and rutin trihydrate inhibited the
      mutagenicity of CSC, but showed confounding effects with SNUS.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7519328
TI  - [Use of health care services by children in the first 2 years of life in The
      Netherlands].
AB  - OBJECTIVE: To assess consumption of medical care for infants and toddlers
      provided by general practitioners and specialists, and of hospital admissions for
      young children. DESIGN: Descriptive. SETTING: Dutch Child Health Clinics (CHC).
      METHOD: An aselect cohort of newborns of 1988/89 of the Social Medical Survey of
      children attending Child health Clinics (SMOCC) were followed for two years; at
      maximally 8 CHC visits data were collected on the preceding interval. RESULTS:
      Health problems as observed in the CHCs like hearing disorders, strabismus,
      congenital hip dysplasia and growth disturbances were present as a cause for
      consultation of a GP or specialist in one out of six. Over 95% of the children
      went to consult their GP, 30% to a paediatrician, 20% to another specialist.
      Twelve per cent of the children was admitted to hospital, 10% of these more than
      once. Accidents caused 10% of all visits to a doctor in primary or secondary
      health care. Children with any form of disability at the age of two (6%) made use
      of the health care system as indicated in this study about three times more
      frequently than the non-disabled children. CONCLUSION: Nearly every child under
      two visited a GP, many a specialist. Timely recognition of specific health
      problems at the CHC prevents delay in treatment, and limits the harm in
      development as well as the costs.

PMID- 7519329
TI  - [Three-and-a-half years' experience with hemodialysis using 37 Permcaths without
      infection or definitive thrombosis].
AB  - 34 patients had 37 Quinton Permcath (PKT), surgically implanted in jugular vein
      (internal: 29, or external: 8). The first 20 were used for a temporary vascular
      access (mean: 21 weeks). Then, the next 17 were used for permanent vascular
      access. 8 could be used for more than 1 year and 2 for more than two years. Anti
      aggregant (29 cases) or anticoagulant treatment (8 cases) were systematically
      prescribed. 6 patients died for unrelated causes (mean delay: 35 weeks). 3
      catheters were mispositioned. 2 catheters had to be removed because they were
      damaged (mean 53 and 69 weeks). Complications were: vein thrombosis (internal
      jugular vein): 2 cases, vein stenosis (inominate vein): 1 case, heparin
      overdoses: 3 cases. A partial thrombosis of a single lumen was common but always
      easily cured by local thrombolysis. Nurses were strongly motivated and followed
      rigorous educations with help of video-movie. This could be why no infectious
      (local or generalised) complication was observed. Long-term Permcath dialysis is
      a precious tool for patient without any peripheral vascular access or in elderly
      and short-live expectancy.

PMID- 7519331
TI  - Are cerebrospinal fluid or urinary monoamine metabolite measures stronger
      correlates of suicidal behavior in depression?
AB  - A series of depressed patients had monoamine metabolites measured in
      cerebrospinal fluid (CSF) and urine. We wished to see if CSF or urinary measures
      were more strongly associated with suicidal behavior in depression. Using a
      variety of graphical and analytic statistical approaches we found that the
      urinary measures of dopamine metabolism had the strongest association with
      suicide attempts in depression. These surprising results suggest that selected
      peripheral correlates of monoaminergic neurotransmission deserve further study in
      suicidal behavior.

PMID- 7519332
TI  - The reliability of urinary 5-HIAA levels.
AB  - Examination of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in
      the urine of psychiatry patients has generally not been used because the
      reliability of urinary 5-HIAA levels has been questioned. Thirty-seven
      generalized anxiety disordered patients collected two consecutive urines for
      measurement of 5-HIAA. The correlation of the 5-HIAA collections was r = 0.82, p
      = 0.0001.

PMID- 7519330
TI  - Comparison of triphenyltetrazolium dye with light microscopic evaluation in a
      rabbit model of acute cerebral ischaemia.
AB  - The present study was performed to compare brain infarct size assessment by
      routine histology (haematoxylin and eosin) and by 2,3,5-triphenyltetrazolium
      chloride staining techniques. New Zealand white rabbits were subjected to
      autologous clot embolization to the anterior circulation of the brain. After a
      study period of 7-8 h the brains were harvested and serially sectioned in the
      coronal plane. Brain slices were then immersed in a 1% triphenyltetrazolium
      chloride dye. Following visualization of the infarcted region, the brains were
      immediately placed in 10% formalin and later prepared for histologic evaluation
      by routine haematoxylin and eosin. The two methods were compared for their
      ability to estimate infarct size by an independent observer. There was excellent
      correlation between the two methodologies; infarct sizes of 57.4 +/- 5.0% versus
      55.9 +/- 5.4% (mean +/- SEM, p < 0.007, r = 0.73, n = 12; expressed as percentage
      of the hemisphere infarcted) were noted for light microscopic evaluation versus
      triphenyltetrazolium chloride staining, respectively. It is concluded that
      triphenyltetrazolium chloride staining is an acceptable method for delineating
      brain infarct size in this rabbit model of thromboembolic stroke. The relative
      ease of infarct size determination with this technique suggests its more
      widespread use in similar models.

PMID- 7519333
TI  - Anomia for people's names.
AB  - The case of an anomia for people's names is reported. The study of this
      dissociation helps to clarify the difference in processing between proper and
      common names. Associated deficits in this and previously described cases provide
      support for the idea that an inability to retrieve arbitrary relations is the
      basis of the naming difficulty. This would confirm the role of proper names as
      purely referring expressions.

PMID- 7519335
TI  - Tachykinergic synaptic inputs to neurons of the medial preoptic region which
      project to the rat arcuate nucleus.
AB  - Anatomical relationships between tachykinin-containing terminals and neurons of
      the medial preoptic area that innervate the arcuate nucleus were studied using
      silver staining of the retrograde tracer wheat germ agglutinin-apoperoxidase-gold
      (WGA-ApoHRP-gold) complex injected in the arcuate nucleus and pre-embedding
      immunocytochemistry for neurokinin A (NKA). At the histological level,
      retrogradely labeled cells not stained for NKA were seen to be surrounded by
      numerous NKA-immunopositive punctate profiles, in particular in the dorsal part
      of the medial preoptic area. At the ultrastructural level, retrogradely labeled
      cell bodies and dendritic profiles displayed highly electron-dense silver
      particle accumulations over the cytoplasm. The were seen in synaptic contact with
      one or several NKA-immunoreactive axon terminals containing small clear vesicles
      and dense-cored vesicles. Such synapses were either symmetrical or asymmetrical.
      The occurrence of synaptic contacts between tachykinin terminals and cells
      innervating the arcuate nucleus in the medial preoptic region provides a
      morphological support for a tachykinergic regulation of preoptic afferences to
      the arcuate nucleus. These results suggest that tachykinins are implicated in the
      indirect control of neuronal activity in the arcuate nucleus notably via the
      preoptic area. Consequently, tachykinins are potentially able to regulate
      indirectly numerous neuroendocrine events involving the tuberoinfundibular
      system.

PMID- 7519334
TI  - Palliative and prophylactic benefits of continuously administered
      dopaminomimetics in Parkinson's disease.
AB  - Motor response complications that ultimately affect most parkinsonian patients
      appear related to altered dopaminergic mechanisms at both the presynaptic and
      postsynaptic levels. "Wearing-off" phenomena reflect a shortened duration of the
      antiparkinsonian action of levodopa, caused initially by the reduced capacity of
      the degenerating nigrostriatal system to store dopamine. Later, secondary changes
      in postsynaptic structures contribute substantially to these complications as
      well as to the changes in levodopa dose-antiparkinsonian response relation and
      the threshold for levodopa-induced dyskinesias that underlie "on-off"
      fluctuations and "peak-dose" dyskinesias. In parkinsonian rats, levodopa
      treatment not only fails to normalize striatal systems modified by the loss of
      dopaminergic afferents, but actually tends to exacerbate these alterations.
      Moreover, the vulnerability of these downstream systems to levodopa-induced
      change appears closely related to the severity of dopamine terminal loss and the
      intermittence of levodopa administration. In parkinsonian patients, switching
      from a standard intermittent levodopa regimen to a continuously infused
      dopaminomimetic alleviates motor fluctuations and widens the therapeutic window
      for levodopa. Taken together, currently available data support the view that
      continuous dopaminomimetic therapy has both immediate and delayed palliative
      value for advanced parkinsonian patients and potentially could confer
      prophylactic benefit to those at earlier stages of their disorder.

PMID- 7519336
TI  - Characterization of a voltage-dependent anionic channel in fused synaptosomes
      isolated from rat hippocampi.
AB  - The inside out configuration of the patch-clamp technique was used to study
      single-channel anionic currents from purified hippocampal synaptosomes fused into
      liposomes to form giant proteoliposomes. At least six different anionic channels
      with unitary conductances of 22-150 pS were found. The most frequently observed
      was the 32-pS conductance channel. This was voltage-dependent; the open
      probability increased from 0.20 at -40 mV to 0.46 at 40 mV. This channel may be
      involved in the repolarization of nerve terminal membranes after an action
      potential, thus, limiting the duration of the spike and the transmitter release.

PMID- 7519337
TI  - Anatomical data supporting the concept of prefrontal influences upon hypothalamo
      medullary relays in the rat.
AB  - Based upon physiological evidence, it has been suggested that the lateral
      prefrontal cortex (LPFC) influences cardiovascular functions by acting upon
      hypothalamic relays to the rostral ventrolateral medulla (RVLM). Presented in
      this paper is preliminary anatomical evidence to support such an hypothesis.
      Using a combination of tracers, it was observed that within the posterolateral
      hypothalamus there was an overlap of input from the LPFC and output to the RVLM.

PMID- 7519338
TI  - N-methyl-D-aspartate receptors modulate extracellular 5-hydroxytryptamine
      concentration in rat hippocampus and striatum in vivo.
AB  - The effects of infusing N-methyl-D-aspartate (NMDA) and the specific NMDA
      receptor antagonist D-2-amino-5-phosphonopropionic acid (D-AP5) into rat
      hippocampus and striatum on extracellular 5-hydroxytryptamine (5-HT) and its
      metabolite 5-hydroxy-indoleacetic acid (5-HIAA) were studied using intracerebral
      microdialysis. In striatum, NMDA (1-100 microM) caused a concentration-dependent
      increase in 5-HT. D-AP5 (10 microM) infusion caused increased extracellular 5-HT.
      When the two drugs were co-infused, no effect on extracellular 5-HT was seen. D
      AP5 alone was found to cause a delayed but sustained increase in dialysate 5
      HIAA. In hippocampus, NMDA infusion caused a dose-dependent decrease in
      extracellular 5-HT while D-AP5 produced a transitory increase in 5-HT level. NMDA
      caused a decrease in dialysate 5-HIAA. In striatum, the effect of 10 microM NMDA
      infusion was abolished by co-infusion with tetrodotoxin (TTX; 1 microM). In
      hippocampus, 1 microM TTX caused a slight but non-significant augmentation of the
      effect of 10 microM NMDA alone. These data indicate that NMDA receptors mediate
      control over 5-HT release and metabolism in different brain regions and may in
      part explain the behavioural effects of non-competitive NMDA receptor
      antagonists.

PMID- 7519339
TI  - Evidence for a regional distribution of hyaluronic acid in the rat brain using a
      highly specific hyaluronic acid recognizing protein.
AB  - By means of a highly specific hyaluronic acid-recognizing protein the
      localization and regional distribution of hyaluronic acid was demonstrated in the
      tel- and diencephalon and in the midbrain of the adult rat nervous system.
      Histochemistry revealed labeling associated with the plasma membrane in highly
      discrete nerve cell bodies of the frontoparietal cortex, the red nucleus, the
      zona reticulata of the substantia nigra, the oculomotor nucleus and the reticular
      thalamic nucleus. A strong labeling without association with perikarya was
      demonstrated in the subgranular zone of the dentate gyrus of the hippocampal
      formation. The present results open up the possibility that the hyaluronic acid
      found in high concentrations associated with some perikarya may have a special
      role in plasticity responses in these discrete nerve cell populations.

PMID- 7519340
TI  - Increased nitric oxide synthase immunoreactivity in rat dorsal root ganglia in a
      neuropathic pain model.
AB  - In rats, tight ligation of L5 and L6 spinal nerves produces symptoms of thermal
      hyperalgesia and mechanical allodynia, mimicking the symptoms which characterise
      painful peripheral neuropathies in humans. Immunoreactivity for nitric oxide
      synthase (NOS) was investigated in lumbar (L1, L4, L5 and L6) dorsal root ganglia
      from naive controls and from rats surviving for 3, 7, and 14 days after
      unilateral ligation of the L5 and L6 spinal nerves. Quantitative analysis
      revealed significant increases in the percentage of NOS-immunoreactive cell
      profiles in L5 and L6 ganglia on the operated side at all time points, with the
      number of labelled profiles increasing with time following ligation, but L1 and
      L4 ganglia were unaffected. These findings suggest that nitric oxide may have a
      role in the generation and/or maintenance of neuropathic pain.

PMID- 7519341
TI  - Clinical immunology and infectious diseases.
AB  - Without the application of immunology, understanding of the pathogenesis and
      pathophysiology of infectious diseases would be severely retarded. The
      development new vaccines for the prevention of infectious diseases has been based
      on new immunologic findings. Immunodiagnostic modalities have provided for the
      growth of diagnostic techniques for infectious diseases. Clinical immunology also
      has laid the groundwork for immunotherapies using the old intravenous
      immunoglobulin preparations and the new monoclonal antibodies, cytokines, and
      interferons.

PMID- 7519342
TI  - Alkaline phosphatase histochemical staining in the study of germinal matrix
      hemorrhage and brain vascular morphology in a very-low-birth-weight neonate.
AB  - We evaluated the utility of alkaline phosphatase (AP) histochemical staining for
      studying intraparenchymal vascular morphology in the brain of a 31-wk-gestation
      (1480 g) neonate who died of respiratory insufficiency after 23 h. In this baby,
      afferent cerebral vessels (arteries, arterioles, and capillaries) stained with
      AP, whereas efferent vessels (venules, veins) did not. The large periventricular
      channels in the germinal matrix were determined to be veins, according to AP
      staining criteria. Arterioles connected with these large periventricular veins
      after passing through 4- to 6-microns capillaries. Branchings and connections of
      the cerebral circulation were conventional; i.e. no arterial rete or
      arteriovenous shunts were found. With this method of differential vascular
      staining, bleeding in the germinal matrix was found to be perivenous only. No
      dilated capillaries or arterioles were seen. Smooth muscle was identified in
      extrastriatal medullary arteries. This preliminary investigation suggests that AP
      histochemical staining is an excellent method for studying brain vascular
      morphology and pathology of the very-low-birthweight neonate.

PMID- 7519344
TI  - Response of colonic smooth muscle from newborn and adult rabbits to electrical
      field stimulation.
AB  - Electrical field stimulation (EFS) of circular smooth muscle from the proximal
      and distal colon of adult rabbits elicits region-specific patterns of contraction
      and relaxation referred to as on and off responses. The present study examined
      EFS-mediated on and off responses in neonatal (3- to 5-d-old), juvenile (2-wk
      old), and adult rabbits to determine whether colonic motility undergoes a period
      of postnatal maturation with respect to the pattern of contraction/relaxation
      that develops in response to stimulation of the enteric nervous system. Muscle
      strips from the proximal and distal colon were oriented parallel to the circular
      muscle layer and stimulated electrically (80 V;0.5-ms pulse width) for 10 s using
      platinum wire electrodes. Stimulus frequency varied between 1 and 64 Hz. EFS
      stimulation of circular smooth muscle from the proximal colon of neonatal,
      juvenile, and adult rabbits was characterized by the development of atropine
      sensitive on-contractions. The frequency-response curves were similar for each
      age group. In the distal colon, EFS of circular smooth muscle from neonatal,
      juvenile, and adult rabbits produced on-relaxations and atropine-insensitive off
      contractions. The frequency-response data for the off-contractions were similar
      for each age group. Although no age-related differences were observed with
      respect to the pattern of contractile response to EFS, the force of the proximal
      colon on contractions and the distal colon off-contractions increased as the
      animals matured. The results suggest that the pattern of colonic enteric
      neurotransmission is established early in the neonatal period and does not
      undergo any significant change during the postnatal period.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7519345
TI  - Pain barriers.

PMID- 7519346
TI  - Developmental outcome of infants treated with extracorporeal membrane oxygenation
      (ECMO) in the neonatal period: is the evidence all in?
AB  - The North American literature was reviewed regarding the developmental outcome of
      infants treated with ECMO therapy versus those infants who received conventional
      medical therapy for treatment of persistent pulmonary hypertension of the
      newborn. The literature reviewed included all ECMO follow-up investigations
      published in medical journals cited in CD-ROM between January 1980 and July 1992,
      as well as abstracts presented at the Society for Pediatric Research 1990-1992.
      The literature was examined with respect to the incidence, prevalence and nature
      of morbidity, with particular attention paid to the neuroevelopmental domains
      assessed, test measures used, age at assessment and criteria for normal and
      abnormal outcome. Rough comparison of the published outcome statistics for the
      cohorts of infants who received neonatal ECMO therapy or conventional medical
      therapy (CMT) suggest equivalent amounts of morbidity within the first few years
      of life. Without appropriate systematic comparison at the same ages on the same
      measures and in infants with equivalent severity of illness, the current
      observations remain tentative at best. Longitudinal investigations are needed in
      order to identify specific medical and developmental markers in infancy of good
      and poor long-term outcome in this population, together with comparisons of
      outcome in the group treated with ECMO versus the group treated with CMT. Fine
      grained, sensitive measures must be employed that record transient or permanent
      delays and/or qualitative deficits in specific skills.

PMID- 7519343
TI  - Energy expenditure and genotype of children with cystic fibrosis.
AB  - Increased energy expenditure, poor dietary intake, and fat malabsorption in
      patients with cystic fibrosis (CF) frequently lead to growth failure and
      malnutrition, which are associated with pulmonary failure and decreased survival.
      The study purpose was to understand better the energy expenditure and
      requirements in the mild pulmonary disease state in children. Resting and total
      energy expenditure were measured in 6- to 9-yr-old, pancreatic-insufficient
      children with CF (n = 25) and control children (n = 25) of similar age, gender,
      and weight. The effect of the most common genotype, homozygous delta F508, on
      energy expenditure was also investigated. Dietary intake, degree of fat
      malabsorption, body composition, physical activity, and clinical status were
      determined. The CF group had a 9% increase in resting energy expenditure, which
      was not related to genotype or severity of lung disease. Both CF genotype
      subgroups (delta F508 homozygous and all others) had a similar, modest resting
      energy expenditure increase. Total energy expenditure was increased by 12% in the
      entire CF group and by 23% in the delta F508 homozygous CF subgroup compared with
      controls. The total energy expenditure increase in delta F508 homozygous children
      may be related to increased voluntary physical activity, reflecting no activity
      reduction associated with lung disease, or to an unidentified genotype-related
      mechanism. The clinical implication is that a detailed physical activity
      assessment should be evaluated along with resting energy expenditure, either
      measured or estimated by equations, when daily energy needs are being determined
      for children with CF.

PMID- 7519349
TI  - Effect of amphiphiles on nitric oxide synthase in endothelial cells.
AB  - Amphiphiles are known to modulate the activity of ATPase, phospholipase A2,
      adenylate and guanylate cyclase amongst others and relax vascular smooth muscle.
      The effect of two amphiphiles, lysophosphatidylcholine (LPC) and digitonin on the
      activity of nitric oxide synthase (NOS), as measured by conversion of
      radiolabeled L-arginine to L-citrulline, has been studied. Neither digitonin
      (0.01 mmol/l) nor LPC (0.01 mmol/l) influenced NOS activity in endothelial cell
      homogenates. Digitonin but not LPC stimulated NOS in intact endothelial cells.
      NOS activity was markedly inhibited by L- but not by D-omega-nitroarginine (D
      NNA, 0.1 mmol/l). L-NNA or D-NNA data demonstrate no effect of amphiphiles on
      isolated NOS. NOS activation may occur as a result of detergent action on the
      membrane.

PMID- 7519348
TI  - Effects of inhibition of nitric oxide synthase on blood-brain barrier transport
      in focal cerebral ischemia.
AB  - This study was performed to determine whether nitric oxide (NO) alters the
      transport of small hydrophilic molecules across the blood-brain barrier in focal
      cerebral ischemia by administering an NO synthase inhibitor, NG-nitro-L-arginine
      methyl ester (L-NAME) and by measuring the blood-brain barrier transfer
      coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C-AIB) in the rats with
      middle cerebral artery occluded under isoflurane anesthesia. L-NAME increased the
      mean arterial blood pressure from 91 +/- 9 to 134 +/- 13 mm Hg. The Ki of the
      ischemic cortex (ICO) was 26% higher than that of the contralateral cortex (CCO)
      in the control animals without the L-NAME treatment. However, in the L-NAME
      treated animals, Ki was 33% lower in the ICO than in the CCO. The Ki of ICO in
      the L-NAME group was significantly lower (-54%) than that of the control group. L
      NAME did not affect Ki significantly in the nonischemic brain regions. Our data
      demonstrate that focal ischemia increased Ki of 14C-AIB, but L-NAME significantly
      decreased the Ki in the focal ischemic area of the brain without causing
      significant changes in the nonischemic tissue. Our results suggest that NO may
      participate in increasing transport of small hydrophilic molecules across the
      blood-brain barrier in focal ischemia.

PMID- 7519347
TI  - [Features of covalent immobilization of catalase on cellulose membranes in
      reverse aerosol OT micelles in heptane].
AB  - Catalase was immobilized on periodate-activated cellulose membranes in a medium
      with the bicarbonate buffer and in reversed micelles of Aerosol OT in heptane.
      The enzyme effectively bound with the carriers in micellar media within a wide
      range of initial concentrations. The efficiency of immobilization depended on the
      volume of the polar phase in heptane, pH, and molarity of the bicarbonate buffer
      in reversed micelles, as well as on the process duration. The catalase covalently
      immobilized on cellulose membranes in reversed micelles was ten times more active
      compared to that immobilized on the same carrier in aqueous medium. Reversed
      micelles stabilized catalase at low concentrations of the enzyme in contact
      solution and hindered its inactivation on the carrier surface.

PMID- 7519350
TI  - Teaching human anatomy in physical therapy education in the United States: a
      survey.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine how human
      anatomy was being taught in physical therapy programs in the United States.
      SUBJECTS: Faculty in 103 physical therapy programs participated in the study.
      METHODS: A six-page questionnaire, which was mailed to 145 physical therapy
      programs, contained five sections: demographics, human gross anatomy--present and
      future, administration/cost, human anatomy textbooks, and human gross anatomy
      content areas. RESULTS: Anatomy was a laboratory-intensive course, with
      dissection being the primary laboratory teaching method. Use of prosected
      specimens, various audiovisuals, and computer-assisted instruction was also
      documented. Half of those teaching anatomy had a degree in physical therapy, and
      65.6% of these educators were doctorally prepared. When comparing anatomy courses
      taught by physical therapy faculty and non-physical therapy faculty, differences
      existed between the two groups with respect to course content and clinical
      applicability. The most significant difference in content area emphasis was noted
      in the thoracic area. CONCLUSION AND DISCUSSION: Differences noted in course
      content emphasis demonstrate the necessity for physical therapy faculty to
      communicate with non-physical therapy faculty teaching human anatomy about course
      content. Although the survey results have indicated that numerous texts are in
      use, the value placed on clinical applicability remains a significant
      consideration.

PMID- 7519351
TI  - Effect of chronic tryptophan depletion on the circadian rhythm of wheel-running
      activity in rats.
AB  - The effect of chronic treatment with a tryptophan (TRP)-free diet on the free
      running circadian wheel-running rhythm and the central serotonergic system was
      investigated in blinded male rats. The long-term TRP-free diet did not change
      periods of activity, but disordered their patterns. This seemed to be due to
      masking, entrainment, enhancement of the morning activity, and obscuring of the
      activity onset as well as appearance of some periodic activities within the
      subjective night. A long-term TRP-fre diet decreased the concentration of TRP, 5
      hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in all brain
      regions tested: frontal cortex, hippocampus, thalamus, hypothalamus, midbrain,
      and pons. Density of 5-HT1A receptor binding was significantly decreased in the
      frontal cortex and hypothalamus, whereas no significant change was observed in
      the density of 5-HT2 receptor binding in all regions. These results suggest that
      the period of primary circadian pacemaker is not affected, but its oscillation,
      as well as the coupling strength between the primary and secondary pacemakers, is
      weakened by the dysfunction of the serotonergic system caused by chronic TRP
      depletion.

PMID- 7519352
TI  - The effect of dextran on microvascular thrombosis in rabbits.

PMID- 7519353
TI  - Nurses persist in persuading patient to be re-intubated.

PMID- 7519354
TI  - The influence of 50 Hz electric and magnetic fields on the extrasystoles of human
      heart.
AB  - This investigation studied the effect of 50 Hz electric and magnetic fields on
      the extrasystoles of human heart. The electrocardiograms (ECG) of 27 transmission
      line workers and 26 male volunteers were recorded with a Holter monitor both in
      and outside the fields. The electric field strength varied from 0.14 to 10.21
      kV/m and the magnetic flux density from 1.02 to 15.43 microT. The measurement
      period was from half an hour to a few hours. Analysis of the ECG recordings
      showed that extrasystoles were as frequent outside the field as in the field. In
      some cases a small decrease in heart rate was observed after field exposure, but
      it is possible that the changes in the pulse rate were caused by small changes of
      work load.

PMID- 7519355
TI  - Chemotherapy of malignant gliomas.

PMID- 7519356
TI  - Radiosurgery/stereotactic external beam radiotherapy for malignant brain tumours:
      the Royal Marsden Hospital experience.
AB  - SRT is a high-precision technique of radiotherapy which delivers focused
      irradiation to small target volumes. In the context of external beam radiotherapy
      it can be described as stereotactically guided conformal radiotherapy. As the
      technique originated from neurosurgical technology, it has initially been limited
      to single fraction treatment. However, with the use of relocatable fixation
      devices the way ahead particularly in its application in the treatment of brain
      tumours is in fractionated SRT. Currently, single fraction SRT/radiosurgery is of
      proven value only in the treatment of small inoperable arteriovenous
      malformations. It is being exploited in the management of brain tumours but so
      far remains as experimental treatment. We have demonstrated that fractionated SRT
      in patients with gliomas is a non-invasive equivalent to brachytherapy and in
      patients with solitary metastases a non-invasive alternative to surgical
      excision. However, the treatment is not without side effects, and the long-term
      effectiveness and toxicity of SRT, particularly with the use of unconventional
      fractionation, is not defined. The future use of SRT in the treatment of brain
      tumours should not be guided simply by the technical possibilities but by a
      rational appraisal of all treatment options to achieve the best disease control,
      survival and toxicity. Although there is potential for benefit in a number of
      small tumours, SRT cannot at present be recommended as the primary treatment in
      any tumour. In addition, its use should be discouraged in the treatment of
      unbiopsied brain lesions and as the major form of treatment of pineal germinomas.
      The technology of stereotactic radiotherapy is evolving, and it is likely that
      SRT will be integrated into conventional radiotherapy practice to become simply a
      high-precision technique of radiotherapy delivery in everyday use.

PMID- 7519357
TI  - Brucella antigens--old dogmas, new concepts.
AB  - A brief review is given on concepts regarding Brucella antigens, principally the
      lipopolysaccharide (LPS) and O-polysaccharide but also, to a minor extent,
      proteins and lipids. Although these views were reported years ago in the
      literature and became widely accepted at the time, many have since been disproven
      with results that have led to exciting new avenues of research and application.
      Where gaps, contradictions and anecdotal observations suggest that the current
      understanding of Brucella is limited, the author has commented on possible
      explanations.

PMID- 7519358
TI  - Responses of human T cells to dominant discrete protein antigens of Escherichia
      coli and Pseudomonas aeruginosa.
AB  - Normal human beings have circulating T lymphocytes that proliferate in response
      to Escherichia coli and Pseudomonas aeruginosa. We performed the present study to
      characterize the nature of the responding T cells and to determine whether
      distinct or shared conventional antigens, superantigens or polyclonal activators
      account for T cell proliferation. Long term antigen-specific T cell lines were
      generated by repeated stimulation of PBMC from four donors with soluble antigen
      preparations of E. coli or P. aeruginosa. This resulted in the emergence of
      distinct T cell populations, which responded to strains of either E. coli or P.
      aeruginosa, but not to both. Trypsin treatment of the bacterial preparations
      largely eliminated their ability to stimulate the T cells. The T cell lines were
      predominantly CD4+ and their proliferation to bacterial antigens was optimal
      using autologous APC. E. coli T cell lines proliferated not only in response to
      the E. coli strain with which they were initially selected, but also to four
      different strains of E. coli, as well as to several related Gram-negative
      species. P. aeruginosa selected T cells exhibited proliferative responses to six
      different P. aeruginosa strains, but not to the other Gram-negative species. The
      finding that repeated stimulation of PBMC with E. coli or P. aeruginosa leads to
      CD4+ T cells highly reactive with conventional protein antigens specific either
      for E. coli or P. aeruginosa indicates that these bacteria possess separate
      dominant protein antigens that drive the proliferation of peripheral blood T
      cells.

PMID- 7519359
TI  - Partial amino acid sequence of a novel protozoan parasite antigen that inhibits
      non-specific cytotoxic cell activity.
AB  - Monoclonal antibody (MoAb) 18C2, prepared against a human EBV transformed
      lymphoblastic cell line (NC-37) is specific for a target cell ligand recognized
      by fish NCC and by mammalian NK cells. MoAb 18C2 inhibits the lysis of a variety
      of transformed murine and human cells (e.g. NC-37, YAC-1, K562, etc.). This MoAb
      also recognizes a determinant on the fish protozoan parasite Tetrahymena
      pyriformis. In the present study, we used MoAb 18C2 to identify a target antigen
      in detergent lysates of T. pyriformis. MoAb 18C2 recognized a 46-50 kDa target
      antigen (NKTag) by Western blot analysis of both crude and ammonium sulphate (AS)
      fractionated (25-40% saturation) T. pyriformis lysates. AS fractionated or
      purified soluble NKTag inhibited NCC mediated lysis of IM-9 target cells in a
      dose dependent fashion. AS fractionated NKTag also inhibited NCC lysis of a
      variety of human and murine transformed targets (e.g. HL-60, MOLT-4, DAUDI, NC
      37, U-937, YAC-1, EL-4). Inhibition was specific for NCC and inhibition could be
      removed by adsorption of AS fractionated NKTag with MoAb 18C2 hybridoma cells.
      NKTag was prepared for amino acid sequencing by preparative SDS PAGE of whole
      cell detergent (CHAPS) lysate followed by Western transfer to nitrocellulose. The
      MoAb 18C2 recognized NKTag was excised and submitted for microsequence analysis.
      Direct N-terminal analysis yielded a 12 residue sequence. Additional sequences,
      obtained from in situ trypsin digests of the NKTag on nitrocellulose yielded four
      additional peptides of 10, 13, 16 and 21 residues. None of the sequences examined
      had significant homology to known sequences (Swiss-Prot protein sequence
      database). These data indicate that MoAb 18C2 recognized a novel protein on T.
      pyriformis which may be involved in target cell recognition/lysis by NCC.
      Further, these data extend our previous observation that a common target
      determinant exists between higher and lower eukaryotic cells, and its expression
      may provide an explanation for the susceptibility of both protozoan parasites and
      transformed tumour cells to NK/NCC lysis.

PMID- 7519361
TI  - NMR solution structure of a peptide nucleic acid complexed with RNA.
AB  - Peptide nucleic acids (PNA) incorporating nucleic acid bases into an achiral
      polyamide backbone bind to DNA in a sequence-dependent manner. The structure of a
      PNA-ribonucleic acid (RNA) complex was determined with nuclear magnetic resonance
      methods. A hexameric PNA formed a 1:1 complex with a complementary RNA that is an
      antiparallel, right-handed double helix with Watson-Crick base pairing similar to
      the "A" form structure of RNA duplexes. The achiral PNA backbone assumed a
      distinct conformation upon binding that differed from previously proposed models
      and provides a basis for further structure-based design of antisense agents.

PMID- 7519360
TI  - Antibodies directed against monomorphic and evolutionary conserved self epitopes
      may be generated in 'knock-out' mice. Development of monoclonal antibodies
      directed against monomorphic MHC class I determinants.
AB  - Beta-2 microglobulin (beta 2m) gene 'knock-out' mice (C1D) were primed with
      purified H-2Kb and H-2Db molecules and spleen cells from immunized mice were used
      to generate monoclonal antibody secreting B-cell hybridomas. Approximately 0.2%
      of the Ig-secreting primary microcultures contained H-2b binding antibodies.
      Three stable anti-MHC class I (MHC-I) antibody secreting hybridoma clones were
      established and subcloned. All three MoAbs precipitated radiolabelled H-2
      molecules as analysed by SDS PAGE, and all three MoAbs stained H-2b, H-2d, as
      well as H-2k cells by FACS analysis. The MoAbs stained to two beta 2m loss mutant
      cell lines, C4.4-25- and R1E, suggesting that some MHC-I heavy chain is exported
      to the cell surface even in the absence of endogenous beta 2m. Staining of murine
      cell lines kept under serum-free culture conditions was strongly influenced by
      the addition of bovine or human serum as a source of exogenous beta 2m suggesting
      that xenogeneic beta 2m affects the conformation of class I molecules.
      Furthermore, all three MoAbs strongly stained the peptide transporter deficient
      cell line, RMA-S, when cultured at 26 degrees C, however, staining was reduced
      five-fold when RMA-S cells were cultured at 37 degrees C. In total, these
      observations suggest that the MoAbs recognize conformational, presumably beta 2m
      and peptide dependent, self epitopes on MHC-class I. One of the three MoAbs
      stained rat blood mononuclear blood cells (BMC), all three MoAbs stained hamster
      BMC, whereas two of the MoAbs stained human cells. These data suggest that the
      MoAbs recognize determinants which are conserved between species. All three
      antibodies strongly inhibited the development of CTLs generated in an allogeneic
      one-way MLC, provided that the MoAbs were present during the first 24 h of
      culture. It is concluded that MoAbs reacting with monomorphic self epitopes may
      be generated using animals deleted of the gene of interest. The implications may
      be far reaching since such MoAbs potentially identify evolutionary conserved and
      physiologically important epitopes.

PMID- 7519362
TI  - Cytokines decrease glutaminase expression in human fibroblasts.
AB  - BACKGROUND: Glutamine metabolism in fibroblasts is essential for energy
      production, nucleotide biosynthesis, and growth during wound healing. Because
      cytokines can impair fibroblast proliferation, we tested the hypothesis that
      cytokines impair glutamine metabolism. We studied the influence of several
      cytokines on the expression of glutaminase, the major enzyme of intracellular
      glutamine metabolism in fibroblasts. METHODS: Human foreskin fibroblasts were
      incubated for 6 and 12 hours with varying doses (10, 100, or 1000 units/ml) of
      interleukin (IL)-1, IL-6, tumor necrosis factor-alpha, or gamma-interferon. Cell
      lysates were assayed for glutaminase-specific activity, and glutaminase protein
      content was measured by Western blotting with a polyclonal antibody. Total
      cellular RNA was extracted, and relative glutaminase messenger RNA levels were
      determined by Northern blotting with a 32P-labeled glutaminase complement DNA
      derived probe. These mRNA levels were normalized by blotting with a beta-actin
      cDNA-derived probe as control. Cell nuclei were isolated, and nuclear run-ons
      were used to determine relative glutaminase mRNA transcription rates. RESULTS: IL
      1, IL-6, tumor necrosis factor-alpha, and gamma-interferon decreased glutaminase
      activity and protein concentration after a 12-hour incubation in a dose
      independent fashion. No difference was noted at 6 hours. Western blot analysis
      showed a 30% to 60% reduction in glutaminase protein in treated cells. These
      cytokines also decreased glutaminase mRNA levels, consistent with transcriptional
      regulation. This was confirmed by nuclear run-on assays that showed a decrease in
      the number of glutaminase transcripts. CONCLUSIONS: A variety of different pro
      inflammatory cytokines decrease glutaminase expression in cultured human
      fibroblasts. This cytokine-mediated inhibition of glutamine metabolism may limit
      the availability of key glutamine-derived intermediates and impair fibroblast
      proliferation in certain patients.

PMID- 7519363
TI  - Prostate specific antigen progression rates after radical prostatectomy or
      radiation therapy for localized prostate cancer.
AB  - BACKGROUND: The purpose of the study was to determine whether a difference is
      noted in the rate of prostate specific antigen (PSA) elevation after radical
      prostatectomy or radiation therapy for localized prostate cancer. METHODS: PSA
      doubling times were calculated by linear regression analysis in 50 patients who
      had been treated by radical prostatectomy and who had three or more increasing
      PSA levels and in 55 patients who had been treated with radiation therapy and who
      had three or more increasing PSA levels. RESULTS: No significant difference was
      noted in the mean PSA doubling times in the two patient groups when stratified by
      the site of tumor recurrence or by pretreatment tumor stage, tumor grade, or acid
      phosphatase level. CONCLUSIONS: Because the PSA doubling time probably parallels
      the tumor growth rate, these data suggest that the malignant potentials of
      recurrent tumor after radical prostatectomy and after radiation therapy are
      equivalent.

PMID- 7519365
TI  - Detrimental effect of nitric oxide synthase inhibition during endotoxemia may be
      caused by high levels of tumor necrosis factor and interleukin-6.
AB  - BACKGROUND: Nitric oxide (NO) production increases during sepsis and endotoxemia.
      Inhibition of NO synthase has been suggested as a therapeutic modality in sepsis
      and endotoxemia, but in recent reports NO synthase inhibition increased mortality
      rate. The mechanism of this phenomenon is not known. Other studies have shown
      that high levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6)
      contribute to death during sepsis and endotoxemia. We tested the effect of NO
      synthase inhibition on survival in endotoxemic rats and hypothesized that
      inhibition of NO synthase during endotoxemia increases circulating levels of TNF
      and IL-6. METHODS: Rats were treated with subcutaneous injection of saline
      solution or 100 mg/kg of the NO synthase inhibitor N-nitro-L-arginine 1 hour
      before intravenous injection of endotoxin (15 mg/kg) or saline solution. Survival
      was followed for 24 hours. Plasma nitrite-nitrate (NO2/NO3), TNF, and IL-6 levels
      were determined at intervals. RESULTS: Endotoxin caused a significant increase in
      levels of plasma NO2-/NO3-, TNF, and IL-6 and a 33% mortality rate. Pretreatment
      with N-nitro-L-arginine increased mortality rate to 74%, decreased NO2/NO3, and
      substantially increased TNF and IL-6 levels. CONCLUSIONS: Inhibition of NO
      synthase increases mortality rate during endotoxemia. The detrimental effect of
      NO synthase inhibition during endotoxemia may be caused by excessive production
      of TNF and IL-6.

PMID- 7519364
TI  - Nitric oxide synthase inhibition exacerbates sepsis-induced renal hypoperfusion.
AB  - BACKGROUND: Hyperdynamic sepsis is often complicated by renal dysfunction, caused
      in part by renal vasoconstriction and impaired blood flow. Nitric oxide (NO) is
      an important mediator of hemodynamic responses to sepsis; however, its importance
      in the renal microcirculation during sepsis is unknown. Our purpose was to
      determine the role of NO in the renal microcirculation during bacteremia.
      METHODS: In vivo videomicroscopy was used to study the microcirculation in five
      groups of hydronephrotic rat kidneys. Cardiac output (CO), mean arterial
      pressure, interlobular artery (ILA) diameter and flow, and afferent (AFF) and
      efferent arteriole diameters were measured. RESULTS: NO synthase inhibition in
      normal rats resulted in hypertension, decreased CO, selective preglomerular
      constriction (ILA, -21%; AFF, -26% of baseline), and hypoperfusion (-56%).
      Escherichia coli resulted in a normotensive, high CO state (+23%) with ILA (-25%)
      and AFF (-20%) constriction and hypoperfusion (-60%). NO synthase inhibition
      during bacteremia normalized CO and increased mean arterial pressure (+34%) but
      exacerbated constriction (ILA, -45%; AFF, -33%) and further impaired flow (-90%).
      CONCLUSIONS: NO maintains preglomerular tone and flow during basal conditions and
      appears to counteract intrarenal vasoconstrictors during E. coli bacteremia.

PMID- 7519366
TI  - Suppression of lipopolysaccharide-induced macrophage nitric oxide and cytokine
      production in vitro by a novel lipopolysaccharide antagonist.
AB  - BACKGROUND: Many of the physiologic derangements resulting in septic shock are
      caused by inflammatory mediators such as nitric oxide (NO) and cytokines produced
      in response to bacterial endotoxin or, more specifically, lipopolysaccharide. The
      recent development of a novel class of lipopolysaccharide antagonists offers the
      opportunity to block this response selectively. In this article we investigated
      the ability of one of these antagonists, B464 (Eisai), to block
      lipopolysaccharide-induced release of macrophage NO and cytokines. METHODS: The
      mouse macrophage cell line RAW264.7 was grown in vitro and exposed to (1) media
      control, (2) B464 alone, (3) lipopolysaccharide alone, or (4) lipopolysaccharide
      plus graded concentrations of B464. Supernatants were assayed for nitrite plus
      nitrate, the stable end products of NO, as well as tumor necrosis factor-alpha
      and interleukin-6. Total cellular RNA was examined for inducible NO synthase and
      interleukin-6 mRNA. RESULTS: Lipopolysaccharide-stimulated increases in NO, tumor
      necrosis factor, and interleukin-6 production were blocked by B464. Reduction of
      NO was also seen at the level of inducible NO synthase mRNA. Induction of
      interleukin-6 mRNA was also suppressed. CONCLUSION: B464 is a novel potent
      specific antagonist of lipopolysaccharide-induced macrophage NO and cytokine
      production.

PMID- 7519367
TI  - Esophageal mucosal blood flow: a central role for calcitonin gene-related
      peptide.
AB  - BACKGROUND: Esophageal mucosal blood flow is a dynamic phenomenon dependent on
      luminal content. Reactive hyperemia, likely a factor in mucosal protection,
      follows luminal exposure to noxious substances, including bile. The mediators of
      this response are unknown, although the likelihood is that visceral afferent
      nerves play a major role. The purpose of this study was to determine whether
      substance P, calcitonin gene-related peptide (CGRP), or adenosine could mediate
      this reactive blood flow response. METHODS: Esophageal mucosal blood flow was
      studied in a rabbit model with the radiolabeled microsphere technique. The effect
      of intraarterial infusion of CGRP and substance P and intravenous adenosine was
      studied. Subsequently, the hyperemic response to luminal deoxycholate was
      measured in the presence of antagonists to CGRP, substance P, and adenosine.
      Immunohistochemical studies were performed to determine the distribution of CGRP
      and substance P in the esophagus. RESULTS: CGRP proved to be a potent stimulus to
      mucosal blood flow. The presence of a CGRP antagonist reduced mucosal blood flow
      at baseline and after exposure to deoxycholate. Antagonists to substance P and
      adenosine had no effect on baseline and deoxycholate-stimulated blood flow.
      CONCLUSIONS: CGRP is likely a major mediator involved in the regulation of
      esophageal mucosal blood flow.

PMID- 7519369
TI  - [The use of exfoliative vaginal cytology for the gynecological evaluation of the
      bitch].
AB  - The relationship between the oestrus cycle of the bitch and the corresponding
      change in vaginal cytology as a reflection of the endocrine situation is
      described. The development of the vaginal epithelium is described using 2
      staining techniques: a modified Papanicolaou-Shorr and the eosin-Thiazin stains.
      The use of vaginal smears in mating determination, oestrus suppression and
      prevention of nidation is discussed and a method of collecting vaginal material
      is described.

PMID- 7519370
TI  - [Recent developments in the diagnosis of parapoxviruses].
AB  - Neutralizing and non-neutralizing monoclonal antibodies against parapoxviruses
      (PPV) were generated by immunizing BALB/c-mice with gradient-purified PPV Orf D
      1701 or purified envelopes. Epitope specificity studies identified three distinct
      epitopes localized in the virus envelope. These antigenic sites allowed a
      differentiation between orf and stomatitis papulosa viruses. For a rapid
      diagnosis of parapoxviruses transmission-electron microscopy, immunofluorescence-
      or immunoperoxidase-staining, antigen capture ELISA, and polymerase-chain
      reaction were used.

PMID- 7519368
TI  - Cyclic strain increases endothelial nitric oxide synthase activity.
AB  - BACKGROUND: Endothelial nitric oxide synthase (eNOS) is an important enzyme that
      controls the production of a potent vascular smooth muscle relaxing factor,
      nitric oxide. However, the role of hemodynamic forces (blood pressure, cyclic
      strain, and shear stress) on the regulation of eNOS has not been fully
      elucidated. Recently, we showed that cyclic strain increases eNOS gene and
      protein in cultured bovine aortic endothelial cells (EC). Because an increase in
      gene transcription and protein synthesis may not necessarily translate into an
      increase in functional activity, the aim of this study was to determine the
      effects of cyclic strain on eNOS activity. METHODS: EC were seeded onto plates
      with flexible bottoms that can be deformed by vacuum and were then exposed to 60
      cycles/minute of either 24% maximum strain (-20 kPa vacuum) or 10% maximum strain
      (-5 kPa vacuum) for 24 hours. eNOS activity was assessed, and nitric oxide
      production was determined (as nitrite) by the Greiss reaction. RESULTS: Twenty
      four percent strain, at 60 cycles/min, but not 10% strain significantly increases
      eNOS activity compared with stationary controls. Both strain regimens increased
      nitric oxide (as nitrite) in culture media compared with stationary controls,
      although nitrite in media of EC exposed to high strain were significantly
      increased compared with the lower strain. CONCLUSIONS: Cyclic strain increases
      eNOS activity in cultured bovine aortic EC. These results may indicate the
      importance of hemodynamic forces in the regulation of eNOS in vivo.

PMID- 7519372
TI  - [Work on a training slide film].

PMID- 7519371
TI  - Sodium cyanide increases cytosolic free calcium: evidence for activation of the
      reversed mode of the Na+/Ca2+ exchanger and Ca2+ mobilization from inositol
      trisphosphate-insensitive pools.
AB  - This study characterized the cytosolic free Ca2+ concentration ([Ca2+]i) in NaCN
      treated human A-431 cells. The resting [Ca2+]i was 85 +/- 8 nM (n = 141) in
      untreated cells at 37 degrees C, determined with the fura-2 fluorescence probe.
      When cells were treated with NaCN, [Ca2+]i increased in a time- and NaCN
      concentration-dependent manner. When cells were exposed to 10 mM NaCN for 10 min,
      [Ca2+]i increased 278 +/- 28% (n = 5) but returned to normal within 45 min after
      treatment. The [Ca2+]i increase depended on the presence of external Ca2+. La3+
      and Cd2+, but not verapamil or nifedipine, inhibited the NaCN-induced [Ca2+]i
      increase. The NaCN-induced [Ca2+]i increase also depended on external Na+ (K1/2 =
      85 mM). The intracellular Na+ concentration, measured with the fluorescence probe
      SBFI, increased 267 +/- 16% after NaCN treatment. The NaCN-induced [Ca2+]i
      increase was modulated by treatment with ouabain or veratridine and was
      completely blocked by tetrodotoxin, amiloride (K1/2 = 5.4 microM), and
      dichlorobenzamil (K1/2 = 0.28 microM). These results suggest NaCN activates the
      Na+/Ca2+ exchange system. TMB-8 and ryanodine both partially blocked the increase
      in [Ca2+]i in the presence of external Ca2+, indicating that Ca2+ release from
      intracellular pools also occurred after the initial Ca2+ influx. NaCN decreased
      inositol trisphosphates production. U-73122, bradykinin, or monensin did not
      prevent the NaCN-induced increase in [Ca2+]i. However, the magnitude of the
      [Ca2+]i increase caused by NaCN was abolished in ionomycin-treated the [Ca2+]i
      increase caused by NaCN was abolished in ionomycin-treated cells, indicating that
      intracellular Ca2+ release induced by NaCN is derived from an ionomycin-sensitive
      Ca2+ pool. The results suggest that NaCN initially increased Na+ influx, which
      activated the reverse mode of a Na+/Ca2+ exchanger, leading to an increase in
      Ca2+ influx. The Ca2+ influx induced a Ca2+ mobilization from only an ionomycin
      sensitive intracellular Ca2+ pool containing ryanodine receptors.

PMID- 7519373
TI  - A G protein involved in nucleocytoplasmic transport: the role of Ran.
AB  - Ran is the only known member of the Ras superfamily of small GTP-binding proteins
      to be localized primarily inside the nucleus. Recently, Ran was unexpectedly
      identified as one of the soluble factors required for nuclear import. As this
      protein has also been implicated in RNA export, nuclear import and export may be
      more closely related than previously thought, with Ran playing a key role in
      each.

PMID- 7519374
TI  - Annexin V: the key to understanding ion selectivity and voltage regulation?
AB  - Annexin V is a Ca(2+)-dependent membrane-binding protein that forms voltage
      dependent Ca2+ channels in phospholipid bilayers and is the first ion channel to
      be structurally and functionally characterized. Data outlined here indicate that
      key amino acid residues act as selectivity filters and voltage sensors, thereby
      regulating the permeability of the channel pore to ions.

PMID- 7519375
TI  - Nuclear localization signal in insulin-like growth factor-binding protein type 3.

PMID- 7519376
TI  - An RNA heresy in the fifties.

PMID- 7519378
TI  - In support of pressure-flow studies for evaluating men with lower urinary tract
      symptoms.

PMID- 7519377
TI  - [High-sulfur protein subunits in keratins].
AB  - The quaternary structure of keratins contains a definite amount (to 40%) of
      protein-subunits with higher content of sulphur composing cystine, cysteine and
      other derivatives of these amino acids. These proteins are characterized by low
      molecular weight (to 30 kDa), significant heterogeneity and disordered, most
      probably, globular ternary structure in a free state. Being a constituent of the
      amorphous part of keratin (the so-called "matrix") and forming numerous intra-
      and intermolecular disulphide links, they stabilize the quaternary structure and
      promote resistance of keratins in solution and action of proteolytic enzymes.

PMID- 7519379
TI  - Why pressure-flow studies should be optional and not mandatory studies for
      evaluating men with benign prostatic hyperplasia.

PMID- 7519380
TI  - Relationship between prostatic epithelial volume and serum prostate-specific
      antigen levels.
AB  - OBJECTIVES: The present study was designed to determine the relationship between
      serum prostate-specific antigen (PSA) levels and prostatic epithelial volumes.
      METHODS: Forty-two men between the ages of 50 and 79 years of age with either an
      abnormal digital rectal examination (DRE) or a serum PSA level > 4 ng/dL
      underwent transrectal ultrasonography (TRUS) and ultrasound-guided random
      systematic biopsy of the prostate. The volumes of the peripheral zone (PZ) and
      transition zone (TZ) were calculated, assuming that the total prostate and TZ are
      ellipsoidal structures. Six random systematic biopsies were directed into the PZ
      and four random systematic biopsies were directed into the TZ under ultrasound
      guidance. Among the 42 patients undergoing prostatic biopsy, adenocarcinoma of
      the prostate was identified in 21 (50%). Tissue sections obtained from the biopsy
      specimens of the subjects without histologic evidence of prostate cancer were
      stained with Mallory trichrome stain, and the percentage area density of
      epithelium in the biopsy cores was determined using computer-assisted color image
      analysis. The relationships between serum PSA and total, PZ, and TZ epithelial
      volumes, and serum PSA and total, PZ, and TZ prostatic volumes were determined
      using regression analysis. RESULTS: The difference between the mean percentage
      epithelial density of the PZ (17.79 +/- 1.40%) and TZ (10.32 +/- 0.82%) was
      statistically significant (p < 0.0001). The mean volumes of epithelium in the PZ
      and TZ were 4.25 +/- 0.47 cc and 3.39 +/- 0.45 cc, respectively. The p and r2
      values for the relationship between serum PSA and total prostatic volume were
      0.016 and 0.260, respectively. Statistically significant correlations were also
      observed between serum PSA levels and TZ epithelial volumes (p = 0.0009; r2 =
      0.449) and serum PSA levels and TZ volumes (p = 0.007; r2 = 0.329). Statistically
      significant correlations were not observed between serum PSA levels and the
      following parameters: PZ volume, PZ epithelial volume, and total prostatic
      epithelial volume. CONCLUSIONS: Although the PZ contains a significantly greater
      area density and absolute volume of epithelium than the TZ, the serum PSA level
      is most strongly correlated only with the volume of epithelium in the TZ.

PMID- 7519381
TI  - Serum prostate-specific antigen, clinical stage, pathologic grade, and the
      incidence of nodal metastases in prostate cancer.
AB  - OBJECTIVES: To evaluate the potential gains in using serum prostate-specific
      antigen (PSA) levels for predicting the incidence of pelvic nodal metastases in
      patients with otherwise localized prostate cancer. METHODS: We reviewed 569
      patients undergoing staging lymphadenectomy, and evaluated the correlation
      between clinical stage, tumor grade, presurgical PSA level, and the incidence of
      nodal metastatic disease using univariate and multivariate regression. RESULTS:
      In univariate analysis stage, grade, and PSA level were highly significant
      covariates with nodal metastasis. Nodal metastatic rates increased as stage
      increased: Stage T1 (A2), 6 of 127 (5%); Stage T2 (B), 41 of 243 (17%); Stage T3
      (C), 95 of 199 (48%), (p < 0.0001). Likewise metastatic rates increased as grade
      increased: Gleason grades 2 to 4, 6 of 124 (5%); Gleason grades 5 and 6, 52 of
      238 (22%); Gleason grade 7, 41 of 122 (34%); Gleason grades 8 to 10, 43 of 84
      (51%) (p < 0.0001). The relationship between PSA level and nodal metastases was
      not linear and we selected the following groupings that correlated with nodal
      disease: 4 or less ng/mL, 4 of 104 (4%); more than 4 to 20 or less ng/mL, 73 of
      335 (22%); more than 20 to 40 or less ng/mL, 35 of 85 (41%); more than 40 ng/mL,
      30 of 45 (67%) (p < 0.0001). Using multivariate logistic regression, stage,
      grade, and PSA were independently predictive of nodal status. CONCLUSIONS: The
      gains in predictive accuracy from PSA beyond that obtained from stage and grade
      were small and in practice would benefit fewer than 15% of our patients. Staging
      pelvic lymphadenectomy remains the only satisfactory method for elucidating nodal
      status in the majority of patients with prostate cancer.

PMID- 7519382
TI  - Post-therapy change in prostate-specific antigen levels as a clinical trial
      endpoint in hormone-refractory prostatic cancer: a trial with 10-ethyl-deaza
      aminopterin.
AB  - OBJECTIVES: Serial changes in prostate-specific antigen (PSA) correlate with
      disease status in all stages of prostatic cancer. For hormone-refractory disease,
      post-therapy declines of 50% and 80% from baseline are associated with an
      improved survival. This study sought to evaluate edatrexate, a synthetic
      antifolate, in hormone-refractory prostatic cancer using post-therapy PSA change
      as the initial endpoint. METHODS: Fourteen patients with progression of disease
      despite castrate levels of testosterone received edatrexate. Serial changes in
      PSA were monitored and correlated with other parameters of outcome. RESULTS:
      Stabilization of a rising PSA level in parallel with clinical stabilization of
      disease was observed in one patient; disease in all others progressed. Toxic
      reactions were acceptable. CONCLUSIONS: With no objective evidence for antitumor
      activity as assessed by post-therapy PSA changes in any of the patients treated,
      edatrexate seems a poor candidate for future study. The use of post-therapy PSA
      change as the initial screening modality allows treatments to be evaluated
      rapidly in patients without measurable disease. The methodology proposed will
      require validation in prospective phase III investigations using survival as the
      endpoint.

PMID- 7519383
TI  - Alpha 1-antichymotrypsin production in PSA-producing cells is common in prostate
      cancer but rare in benign prostatic hyperplasia.

PMID- 7519384
TI  - Worldwide pattern of mortality from motor vehicle accidents, 1950-1990.
AB  - Trends in age-specific and age-standardized death certification rates from motor
      vehicle accidents over the period 1950-1990 were analyzed for 48 countries from
      four continents (2 from North America, 10 from Latin America, 8 from Asia, 26
      from Europe, Australia and New Zealand) on the basis of data produced by the
      World Health Organization mortality database. In most developed western and
      Asiatic countries, mortality rates increased until the late 1960's or early
      1970's, and declined thereafter to reach values often lower than those of the
      early 1950's, although the number of circulating vehicles has substantially
      increased over the same calendar period. The extent of the decline was, however,
      different in various countries, as well as in the two sexes and in various age
      groups, thus leading to complex cohort and period patterns. In general, countries
      (like the U.S.A. or U.K.), where the number of motor vehicles had increased
      earlier, have now comparatively higher rates at younger than at middle and older
      age, while the opposite is observed in countries with later spread of motor
      vehicles. Further, there were a few countries, including Kuwait, Venezuela and
      several other Latin American countries, Australia and New Zealand, and several
      southern and eastern European countries, with exceedingly high rates from motor
      vehicle accidents, and where comprehensive interventions on this important cause
      of death are therefore a public health priority.

PMID- 7519386
TI  - [The determination of neurospecific proteins in the blood of patients with closed
      craniocerebral trauma and their diagnostic significance].
AB  - Data are reported on the content of neurospecific proteins in the blood serum of
      87 patients with closed head injuries. It has been established that the method of
      competent EIA can be used for measuring the content of neurospecific proteins. It
      has also been shown that their content in the blood depended on the severity of
      injury: the more severe injury the higher the protein content. Some aspects have
      been revealed of the blood content of protein 14-3-2 and total myelin protein.
      The authors discuss a possible diagnostic importance of these proteins in the
      differential diagnosis of the severity of closed head injuries and in the
      determination of lesions of the neuroglia and neurons both in mild and grave
      trauma.

PMID- 7519387
TI  - [The characteristics of the physical, neuropsychic and somatic development of the
      children of alcoholic parents].
AB  - Analysis was made of the physical, neuropsychic and somatic development of
      children whose patients suffered from chronic alcoholism as compared to the
      control group children. Retardation in the physical development (primarily in
      body weight with alcoholic mother, in the height with alcoholism of father or of
      both parents) and in the neuropsychic development, the higher general somatic and
      infection morbidity, the increased level of the stigmas of dysembryogenesis and
      developmental abnormalities were detectable significantly more frequently.

PMID- 7519388
TI  - Developmental studies on vasoactive intestinal peptide, substance P and
      calcitonin gene-related peptide in salivary glands of postnatal rats.
AB  - The development of vasoactive intestinal peptide, substance P and calcitonin gene
      related peptide in parotid, submandibular and sublingual glands of the male rat
      was followed by immunochemistry and immunocytochemistry. The total amounts of
      these peptides increased in surges during the first 8 weeks of the animal's life;
      one within 2-4 weeks and the other beginning 1-2 weeks later. Nerve fibres
      containing these peptides were present at birth showing a pattern of distribution
      similar to that in adults. During the first 4 weeks the nerve fibres increased in
      number.

PMID- 7519389
TI  - CGRP (8-37) reduces the duration but not the maximal increase of antidromic
      vasodilation in dental pulp and lip of the rat.
AB  - In this study the newly developed blockers of substance P (CP-96,345) and
      calcitonin gene-related peptide (CGRP8-37) were used to examine whether substance
      P and CGRP are involved in the afferent nerve induced vasodilation in the rat
      lower incisor pulp and lip. Electrical stimulation of the inferior alveolar nerve
      (10 V, 2 ms, 10 Hz, 30 s) in the presence of phenoxybenzamine (3 mg kg-1) induced
      an immediate vasodilation in the pulp and lip (52 and 186% increase in blood flow
      respectively, n = 12) with a long duration. Infusion of 2 mg kg-1 CP-96,345, a
      dose that inhibited the vasodilator effects of substance P (5-25 ng kg-1) in oral
      tissues, did not have any effect on antidromic vasodilation in either tissue.
      After infusion of CGRP8-37 (0.3 mg kg-1) the duration of the antidromic
      vasodilation in the pulp and lip was significantly reduced by 72 and 67%
      respectively (P < 0.05, n = 4), whereas the maximal increase of the response was
      unaffected. The blocking effect of the drug was short-lasting. When combined
      infusions of CP-96,345 and CGRP8-37 were given, a similar reduction in the
      duration of antidromic vasodilation in the pulp and lip occurred but in this case
      the amplitude of vasodilation in the pulp was reduced (from 35 +/- 9 to 12 +/-
      3%, P < 0.05, n = 4). However, in the lip, the amplitude of vasodilation was not
      significantly reduced. The present findings indicate an involvement of CGRP in
      the mediation of the late phase of antidromic vasodilation in rat oral tissues
      and a role of substance P in the initiation of antidromic vasodilation in the
      incisor pulp.

PMID- 7519385
TI  - [The extravascular contractile system of the human placenta: a new aspect for
      function of the organ?].
AB  - In the chorionic plate and stem villi of the human placenta besides the fetal
      blood vessel system a second extravascular contractile system (EVCS) exists. The
      cells of this system contain contractile and intermediate filaments and are
      dipeptidyl peptidase-IV- and NO-synthase-type-I-(NOS)-immunoreactive. Therefore
      it can be assumed that these cells cleave the vasodilator Substance P (by DPP IV)
      and produce NO (by NOS) and may contribute to a modulation of the EVCS.

PMID- 7519390
TI  - Long-term results with MACOP-B in the treatment of aggressive non-Hodgkin's
      lymphomas. The experience in Brazil.
AB  - From October 1984 to December 1989, 59 patients with aggressive non-Hodgkin's
      lymphomas (diffuse mixed, diffuse large cell, and immunoblastic) were treated
      with MACOP-B. All patients were previously untreated and most of them had
      advanced disease. Complete response (CR) was observed in 66%. Actuarial overall
      survival, failure-free survival (FFS), and relapse-free survival at 8 years were
      54%, 52%, and 81%, respectively, with a median follow-up of 76 months (range: 28
      92 months). The presence of B symptoms influenced significantly the CR rate,
      while FFS was affected by B symptoms, bone marrow involvement, and number of
      extranodal sites. Toxicity was high, with mucositis grade 2 or 3 occurring in
      70%, leukopenia grades 3 or 4 in 80%, and death in 11.8% of the patients. MACOP-B
      was active in the treatment of aggressive non-Hodgkin's lymphomas, mainly in
      patients with few poor-prognosis factors, but other less toxic regimens would be
      more appropriate for this population. For poor-prognosis patients, new
      therapeutic modalities are necessary.

PMID- 7519391
TI  - Radiotherapy of refractory bone pain due to systemic mast cell disease.
AB  - Systemic mastocytosis is a rare disease characterized by mast cell infiltration
      of organs. Bony pain is present in up to 28% of cases and is frequently chronic
      and difficult to palliate. Historical attempts at pain control have exclusively
      involved medical therapy. We report three cases of refractory bone pain in two
      patients with advanced systemic mast cell disease and associated bony
      involvement, which were treated with radiotherapy. This report represents some of
      the first uses of radiotherapy in this disease. Two patients with a primary
      diagnosis of systemic mastocytosis and bony pain unresponsive to medical therapy
      were referred for palliative radiotherapy. In the first case, referral was made
      because of a painful thoracolumbar spine and left shoulder, and in the second,
      for bilateral lower extremity pain. Patients were irradiated on megavoltage
      equipment to 30 Gy in 200 and 300 cGy daily fractions. For the first patient,
      treatment reduced pain scores from 8/10 (severe) to 3-4/10 (moderate) by 1 month
      posttreatment, with subsequent varying pain until his death 4 months after his
      second treatment. The second patient achieved pain relief from 10/10 pretreatment
      to 1-2/10 while on treatment. This proved durable for 9 months until her death
      due to disease progression. The first patient had a slight exacerbation of his
      thrombocytopenia during his initial treatment, but otherwise neither patient
      experienced any acute complications from the radiation treatments. When patients
      with advanced systemic mastocytosis require large narcotic doses for incomplete
      bone pain control associated with demonstrable bony involvement, the relatively
      slight risks of palliative radiation to bone may be favorably weighed against the
      likelihood of pain relief.

PMID- 7519392
TI  - Palliation of carcinoma of the esophagus: is there a hope for cure?

PMID- 7519393
TI  - Role of membrane trafficking in plasma membrane solute transport.
AB  - Cells can rapidly and reversibly alter solute transport rates by changing the
      kinetics of transport proteins resident within the plasma membrane. Most notably,
      this can be brought about by reversible phosphorylation of the transporter. An
      additional mechanism for acute regulation of plasma membrane transport rates is
      by the regulated exocytic insertion of transport proteins from intracellular
      vesicles into the plasma membrane and their subsequent regulated endocytic
      retrieval. Over the past few years, the number of transporters undergoing this
      regulated trafficking has increased dramatically, such that what was once an
      interesting translocation of a few transporters has now become a widespread
      modality for regulating plasma membrane solute permeabilities. The aim of this
      article is to review the models proposed for the regulated trafficking of
      transport proteins and what lines of evidence should be obtained to document
      regulated exocytic insertion and endocytic retrieval of transport proteins. We
      highlight four transporters, the insulin-responsive glucose transporter, the
      antidiuretic hormone-responsive water channel, the urinary bladder H(+)-ATPase,
      and the cystic fibrosis transmembrane conductance regulator Cl- channel, and
      discuss the various approaches taken to document their regulated trafficking.
      Finally, we discuss areas of uncertainty that remain to be investigated
      concerning the molecular mechanisms involved in regulating the trafficking of
      proteins.

PMID- 7519394
TI  - Picomolar doses of substance P trigger electrical responses in mast cells without
      degranulation.
AB  - The nervous and immune systems may communicate through the action of
      neurotransmitters on mast cells. We used patchclamp electrophysiology to assess
      the responses of rat peritoneal mast cells (PMC) to low levels of substance P
      (SP), which are likely to occur in situ. SP at 50 nM, or even 10,000 times
      reduced to 5 pM, triggered an outwardly rectified Cl- current (50 nM: 10 of 10
      cells; 5 pM: 10 of 11 cells), although degranulation never occurred. Electrical
      responses were delayed (mean 102.6 s for 5 pM SP), appearing as brief current
      pulses. Reapplication of SP resulted in peak current augmentation (mean 15.3 pA
      before exposure to SP, 47.3 pA after 1st exposure, and 116.0 pA after 2nd
      exposure to 5 pM SP). Cells repetitively exposed to SP degranulated 5-15 min and
      > 25 min after the second exposure to 50 nM SP (10 of 10 cells) or 5 pM SP (5 of
      9 cells), respectively. This effect was reduced by 10 microM 5-nitro-2-(3
      phenylpropylamino)benzoic acid or when extracellular Ca2+ was removed, indicating
      a dependence on Cl- conductance and extracellular Ca2+. We propose that whole
      cell current oscillations in the absence of degranulation are the functional
      correlate of priming, a process that increases cellular responsiveness for the
      subsequent stimulation.

PMID- 7519395
TI  - Epithelial Ca2+ channels sensitive to dihydropyridines and activated by
      hyperpolarizing voltages.
AB  - Parathyroid hormone (PTH) increases transcellular Ca2+ absorption in renal
      cortical thick ascending limbs and distal convoluted tubules (DCT). In cells
      isolated from these nephron segments, PTH increases Ca2+ uptake by a pathway that
      is sensitive to dihydropyridine-type agonists and antagonists (B. J. Bacskai and
      P. A. Friedman. Nature Lond. 347: 388-391, 1990). Patch-clamp techniques were
      used to identify Ca(2+)-permeable channels in DCT cells. Channel activity was
      detectable in cell-attached patches only in cells pretreated with PTH. Ca2+
      channels exhibited prolonged open times (seconds), had a low single-channel
      conductance (2.1 pS), and open channel probability increased at hyperpolarizing
      voltages (-50 to -90 mV). Channel activity was sensitive to dihydropyridine-type
      compounds, nifedipine, and BAY K8644, as was Ca2+ uptake. However, Ca2+ entry was
      insensitive to verapamil or omega-conotoxin. These results demonstrate that these
      channels mediate PTH-stimulated apical membrane Ca2+ entry in DCT cells, which
      are the principal Ca(2+)-transporting cells of the kidney.

PMID- 7519396
TI  - Coordination of nuclear and mitochondrial gene expression during the development
      of cardiac hypertrophy in rats.
AB  - We studied the coordination of nuclear and mitochondrial gene expression during
      cardiac hypertrophy following aortic stenosis or thyroid hormone treatment in
      rats. We measured mRNA levels for representative subunits of cytochrome-c
      oxidase, two encoded by mitochondrial DNA and two encoded by the nucleus, as well
      as the levels of one mitochondrial rRNA. In both models of hypertrophy, an
      increase of total tissue RNA, reflecting mainly cytosolic ribosomes, accompanied
      the increase in ventricular weight. Relative levels of mitochondrial rRNA
      remained unchanged, indicating a net synthesis of mitochondrial ribosomes as
      well. In both models, cytochrome-c oxidase activity and nuclear-encoded mRNAs
      remained fairly constant, whereas levels of mitochondrial mRNAs were transiently
      decreased 24 h after the growth stimulus. We conclude that, in the initial phase
      of hypertrophy, the signal regulating the synthesis of mitochondrial rRNA is
      synchronized with nuclear gene expression, whereas the signal regulating
      mitochondrial mRNA synthesis is not. We postulate that differential regulation of
      mitochondrial transcription and premature termination of the polycistronic
      transcript (the latter giving rise to the mitochondrial rRNAs) account for the
      observed results.

PMID- 7519397
TI  - Ketoconazole blocks organic osmolyte efflux independently of its effect on
      arachidonic acid conversion.
AB  - Ketoconazole, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate, and gossypol are
      reported inhibitors of the lipoxygenase (LO) and cytochrome P-450 enzyme systems
      and are potent blockers of swelling-activated efflux of organic osmolytes and
      volume-sensitive anion channels in C6 glioma cells. To directly test the
      hypothesis that LO- or cytochrome P-450-derived products of arachidonic acid (AA)
      participate in the regulation of these volume-sensitive transport pathways, we
      incubated C6 cells with [1-14C]AA and observed the extent and profile of its
      conversion under basal conditions and after acute swelling. High-performance
      liquid chromatographic analysis revealed that most (70-80%) of the labeled AA
      remained unchanged with only 6-8% and 10-20% of label converted to LO- [12(S)-
      and 15(S)-hydroxyeicosatetraenoic acid (12- and 15-HETE)] and cyclooxygenase-
      [prostaglandin (PG) E2 and PGF2a] derived products, respectively. Leukotrienes
      and epoxyeicosatrienoic acid compounds were not produced. The conversion profile
      of [1-14C]AA was not altered substantially by cell swelling. Treatment of cells
      with the LO-derived products 5-, 12-, and 15-HETE or their immediate metabolic
      precursors, 5(S)-, 12(S)-, and 15(S)-hydroxyperoxyeicosatetraenoic acid, at 5
      microM concentrations did not stimulate efflux of [3H]inositol. In addition,
      treatment with HETEs did not override the inhibition of efflux observed with the
      LO-cytochrome P-450 blocker ketoconazole. Whole cell patch-clamp experiments
      demonstrated that volume-sensitive anion channels, the postulated pathway for
      organic osmolyte efflux in C6 cells, are rapidly and reversibly blocked by
      ketoconazole in a fashion suggestive of direct inhibition rather than via
      interruption of a second messenger pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519398
TI  - Heterotrimeric G proteins, vesicle trafficking, and CFTR Cl- channels.
AB  - Previously (E.M. Schwiebert, N. Kizer, D. C. Gruenert, and B. A. Stanton, Proc.
      Natl. Acad. Sci. USA 89: 10623-10627, 1992), we showed that heterotrimeric G
      proteins regulate adenosine 3',5'-cyclic monophosphate (cAMP)-activated cystic
      fibrosis transmembrane conductance regulator (CFTR) Cl- channels in human airway
      epithelial cells. The goal of the present study was to test the hypothesis that
      heterotrimeric G proteins regulate vesicle trafficking and exocytosis and that
      these events are critical for cAMP activation of CFTR-mediated Cl- secretion. We
      report that cAMP stimulates exocytosis and CFTR Cl- conductance (GCl) in normal
      but not in CF cells. Stimulation of the heterotrimeric G protein G alpha i-2
      inhibited cAMP-activated CFTR GCl and exocytosis in normal cells. In contrast,
      inhibition of G alpha i-2 stimulated exocytosis and allowed cAMP to stimulate
      CFTR GCl in cells isolated from patients with cystic fibrosis (CF). Brefeldin A
      and nocodazol prevented cAMP-induced exocytosis and also blocked cAMP stimulation
      of CFTR GCl in normal airway epithelial cells. Our studies suggest that the
      heterotrimeric G protein G alpha i-2 regulates CFTR GCl in human airway
      epithelial cells by modulating vesicle trafficking and the delivery of CFTR Cl-
      channels from an intracellular vesicular pool to the plasma membrane. Inhibition
      of G alpha i-2 may be a useful therapeutic approach to target mutant delta F508
      CFTR Cl- channels from an intracellular vesicular pool to the plasma membrane and
      thereby correct defective Cl- secretion in CF airway epithelial cells.

PMID- 7519399
TI  - Expression of a rabbit renal ascorbic acid transporter in Xenopus laevis oocytes.
AB  - We examined the expression of renal ascorbic acid transporter(s) in Xenopus
      laevis oocytes after microinjection of cells with poly(A)+ RNA extracted from
      rabbit kidney cortex. Concomitant expression of the Na+-glucose cotransporter
      served as a control in these studies. Injection of poly(A)+ RNA into oocytes
      produced over a fivefold increase in the uptake of [14C]ascorbic acid (570
      microM) compared with water-injected cells. Size fractionation of the kidney
      cortex mRNA by sucrose gradient revealed that the mRNA species that induced
      ascorbic acid transporter expression in oocytes was present in a fraction
      centered around 2.0 kilobases (kb) and had a size range of 1.8-3.1 kb. Injection
      of the active fraction into oocytes produced a > 40-fold increase in ascorbic
      acid uptake compared with water-injected controls. Expression of ascorbic acid
      transporter(s) was noticeable as early as 2 days after injection and was maximal
      after 7 days; it was also dependent on the amount of mRNA injected into oocytes.
      The induced uptake of [14C]ascorbic acid after injection of mRNA into oocytes was
      1) Na+ dependent, as indicated by the almost complete lack of transport on
      removal of Na+ from the incubation medium; 2) significantly inhibited by
      unlabeled ascorbic acid and its structural analogue isoascorbic acid but not by D
      glucose; and 3) saturable as a function of increasing the substrate concentration
      in the incubation medium (100-1,000 microM), with an apparent Km of 258 +/- 72.5
      microM and a maximum velocity of 29.6 +/- 2.8 pmol.oocyte-1.2 h-1. These data
      demonstrate that X. laevis oocytes are a suitable system to functionally express
      the mammalian renal ascorbic acid transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519401
TI  - Osmotic and other properties of isolated human cheek epithelial cells.
AB  - This study describes some biological properties of human cheek (buccal
      epithelial) cells, isolated by mouth wash. Yields ranged from 6.5 to 20.6 x 10(6)
      cells, with a mean (+/- SE) of 12.2 +/- 4.2 x 10(6) cells, which gave 0.55 +/-
      0.01 x 10(6) cells/mg protein. Vital stain exclusion was similar in cells
      isolated in either water (89 +/- 2%) or 250 mM sucrose (87 +/- 3%). From our
      measurements of cell volume and electrolyte content, we estimated intracellular
      Na+ and K+ concentrations to be between 0.3-0.5 and 7.4-13.0 mM, respectively. In
      22 adult subjects, basal, prickle, intermediate, and superficial cells
      represented 0.3 +/- 1.4, 51 +/- 2.4, 26 +/- 0.9, and 22.7 +/- 1.8%, respectively,
      of the total sample. Cheek cells exhibited a low endogenous rate of oxygen
      consumption, which was stimulated by glucose or succinate and inhibited by KCN or
      NaF. Cheek cells were osmotically stable in a wide range of media, including
      water. However, they exhibited shrinkage and collapse in hypertonic media,
      particularly polyethylene glycol.

PMID- 7519400
TI  - Tyrosine kinase involvement in IL-1 beta-induced expression of iNOS by beta-cells
      purified from islets of Langerhans.
AB  - Nitric oxide is believed to mediate the inhibitory effects of cytokines on
      glucose-stimulated insulin secretion by both rat and human islets. The aims of
      this study were 1) to determine the cellular source of the cytokine-inducible
      isoform of nitric oxide synthase (iNOS) expressed in islets following cytokine
      stimulation and 2) to determine whether tyrosine kinase activity participates in
      cytokine-induced iNOS expression. In this report we demonstrate that the cytokine
      interleukin-1 beta (IL-1 beta) stimulates the expression of iNOS and the
      formation of nitric oxide (as determined by nitrite formation, a stable oxidative
      product of nitric oxide) by isolated intact rat islets and by primary beta-cells
      purified by fluorescence-activated cell sorting (FACS). Both the expression of
      iNOS and nitrite formation induced by IL-1 beta were prevented by the mRNA
      transcriptional inhibitor actinomycin D. IL-1 beta did not induce the expression
      of iNOS by FACS-purified alpha-cells, the other major endocrine cell type of the
      islet. The tyrosine kinase inhibitors genistein and herbimycin A prevented IL-1
      beta-induced expression of immunoprecipitable iNOS and nitrite release by islets,
      by insulinoma RINm5F cells, and by FACS-purified beta-cells. Herbimycin A and
      genistein also prevented IL-1 beta-induced iNOS mRNA accumulation as determined
      by Northern blot analysis of total RNA isolated from RINm5F cells. These findings
      indicate tyrosine kinase activation participates in IL-1 beta-induced expression
      of iNOS by the insulin-secreting beta-cell.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519402
TI  - Nonparallel secretion of GP-2 from exocrine pancreas implies luminal coupling
      between acinar and duct cells.
AB  - The in vivo and in vitro secretion of glycoprotein-2 (GP-2), a glycosyl
      phosphatidylinositol (GPI)-anchored protein from the rat exocrine pancreas, was
      characterized. GP-2 was secreted in a nonparallel manner compared with amylase, a
      marker of secretory enzymes. Attenuated GP-2 secretion correlated with hormones
      that stimulated exocytosis in acinar cells. Augmented GP-2 secretion correlated
      with hormones that stimulated fluid and bicarbonate secretion from ductal
      elements. Immunofluorescence studies identified an enriched pool of GP-2 tightly
      bound to the apical membranes of acinar cells in addition to zymogen granules.
      This non-zymogen granule pool appears to represent the source of GP-2 released
      from acinar cells in a nonparallel manner. With the use of dispersed pancreatic
      acini largely devoid of ductal elements, GP-2 release was found to be augmented
      by alkaline pH. Thus GP-2 secretion appears to be modulated by two discrete
      cellular processes: 1) delivery of prereleased GP-2 within zymogen granules to
      the ductal lumen by exocytic mechanisms and 2) enzymatic release of GPI-anchored
      GP-2 from the luminal membranes, a kinetic process that appears to be regulated
      by secretin- or carbachol-induced secretion of bicarbonate.

PMID- 7519403
TI  - Dexamethasone inhibits IL-1 and TNF activity in human lung fibroblasts without
      affecting IL-1 or TNF receptors.
AB  - Interleukin (IL-1) and tumor necrosis factor (TNF) activate human lung
      fibroblasts through interactions with specific receptors. One effect of this
      interaction of IL-1 and TNF with fibroblasts is an increased production of the
      cytokines, IL-6 and IL-8. Dexamethasone blocks the induction of IL-6 and IL-8 by
      IL-1 or TNF. In these studies, we determined whether dexamethasone interferes
      with the upregulation of IL-6 and IL-8 by downregulating expression of the IL-1
      or TNF receptor genes. Confluent lung fibroblasts were treated with medium alone
      (control) or medium with dexamethasone (10(-6) M). Dexamethasone did not decrease
      the binding of IL-1 and TNF to their receptors, nor did it decrease amounts of IL
      1 or TNF receptor RNA. Both IL-1 and TNF increased release of IL-6 and IL-8 from
      the cells in a dose-dependent manner and dexamethasone inhibited this effect.
      Dexamethasone also inhibited the induction of IL-6 and IL-8 RNA by IL-1 and TNF.
      The studies show that dexamethasone does not block the effects of IL-1 or TNF on
      fibroblasts by decreasing expression of IL-1 or TNF receptors.

PMID- 7519404
TI  - Acidification of vasopressin-induced endosomes in toad urinary bladder.
AB  - It is well established that water channels (WC) are removed from the apical
      membrane of vasopressin-sensitive epithelia by endocytosis. The processing and
      the ultimate fate of endocytosed WC is, however, incompletely understood. In many
      cells, endosome acidification plays an important role in the processing and
      sorting of endocytosed proteins. Endosome acidification in the toad urinary
      bladder was therefore examined in vivo by fluorescence ratio video microscopy
      after induction of endocytosis by vasopressin removal and transepithelial water
      flow in the presence of the pH-sensitive fluid phase marker 2',7'-bis(2
      carboxyethyl)-5(6)-carboxyfluorescein-dextran. Fifteen minutes after induction of
      endocytosis, the majority of endosomes had a neutral or slightly acidic pH. The
      number of acidic endosomes increased progressively with time. Two hours after
      endocytosis began, 98% of the endosomes had a pH < 6.0. Bafilomycin completely
      blocked endosome acidification, indicating that H+ transport is mediated by a
      vacuolar H(+)-adenosinetriphosphatase. Bafilomycin had no effect on
      transepithelial water flow in bladders repetitively stimulated by vasopressin.
      These findings, as well as the work of other investigators, suggest that if WC
      recycling occurs, it is not dependent on acidification of the endosomal
      compartment. Acidification of vasopressin-induced endosomes most likely
      represents a terminal event in the endocytic pathway.

PMID- 7519405
TI  - Acute renal effects of neutral endopeptidase inhibition in humans.
AB  - The acute renal effects of neutral endopeptidase 24.11 (E-24.11) inhibition
      induced by a single oral dose of sinorphan (100 mg) were investigated in 10
      healthy normotensive subjects on normal sodium diet. Sinorphan inhibited 90% of E
      24.11 activity and increased plasma atrial natriuretic peptide (ANP) and urinary
      guanosine 3',5'-cyclic monophosphate (cGMP) by 70 and 100%, respectively.
      Sinorphan increased urinary sodium output by 50% (P < 0.001) and decreased
      fractional distal reabsorption by 4% (P < 0.01). Sinorphan increased glomerular
      filtration rate (GFR) and filtration fraction by 10% 1 h after administration and
      decreased renal plasma flow by 10%. Mean arterial pressure, renal vascular
      resistance, plasma aldosterone concentration, and renin activity were unmodified.
      Sinorphan decreased fractional clearance of neutral dextrans over the 34- to 52-A
      radius range. Applying the changes along with a hydrodynamic isopore with shunt
      model, sinorphan significantly increased capillary pressure gradient (delta P; 39
      +/- 1 vs. 34 +/- 1 mmHg; P < 0.01), whereas ultrafiltration coefficient was
      unchanged. In conclusion, endopeptidase inhibition increased endogenous plasma
      ANP and cGMP generation and induced natriuresis through both an increase in
      filtered load and a decrease in distal tubular reabsorption of sodium. Sinorphan
      increases GFR, filtration fraction, and delta P, probably through an increase in
      efferent over afferent arteriolar resistance ratio.

PMID- 7519407
TI  - Permissive role of prostacyclin in cerebral vasodilation to hypercapnia in
      newborn pigs.
AB  - Hypercapnic cerebral vasodilation in piglets is accompanied by increased cerebral
      prostanoid synthesis. Interventions that prevent the increased prostanoids also
      interfere with the vasodilation. However, the increased prostanoids may not
      produce vasodilation directly; instead, they may allow or enhance function of
      another mechanism. The present experiments examined the hypothesis that
      prostacyclin can allow, but may not directly produce, cerebral vasodilation to
      hypercapnia. Chloralose-anesthetized piglets were equipped with closed cranial
      windows for measurements of pial arteriolar diameters. Hypercapnia (arterial CO2
      partial pressure approximately 70 mmHg) was administered before and after
      indomethacin (5 mg/kg iv) in all animals. Then artificial cerebrospinal fluid
      (aCSF) under the cranial window was replaced for the remainder of the experiment
      with aCSF containing vehicle, carbaprostacyclin (60 pM), iloprost (1 pM),
      prostaglandin E2 (PGE2; 1.7 and 3.3 nM), isoproterenol (10 and 100 nM), or sodium
      nitroprusside (1 microM), and hypercapnia was repeated. The two prostacyclin
      receptor agonists restored cerebral vasodilation to hypercapnia that had been
      blocked by indomethacin (to 92 +/- 31% and 76 +/- 11% of the before-indomethacin
      dilation for carbaprostacyclin and iloprost, respectively.) The highest dose of
      PGE2 partially restored the dilation (43 +/- 7% of the pre-indomethacin
      response). In contrast, neither isoproterenol nor sodium nitroprusside permitted
      significant dilation to hypercapnia following indomethacin treatment. These data
      indicate that prostacyclin can allow hypercapnic vasodilation to occur, but
      increasing levels do not appear to be necessary to cause the dilation directly.
      The short half-life of prostacyclin may explain why active prostanoid synthesis
      appears to be necessary for hypercapnia-induced cerebral vasodilation in newborn
      pigs.

PMID- 7519406
TI  - Aftereffects of high-intensity DC stimulation on the electromechanical
      performance of ventricular muscle.
AB  - To clarify the mechanisms underlying cardiac dysfunction after electrical
      defibrillation, we investigated the effects of direct current field stimulation
      (10 ms, 1-80 V/cm) on isolated guinea pig papillary muscles. Shocks (S2) > 15
      V/cm lowered the plateau height of the S2-induced action potential and inhibited
      its terminal repolarization. Subsequent responses to basic stimuli (S1, 1.0 Hz)
      for 1-3 min were characterized by a decrease in the maximum diastolic potential,
      a shortening of action potential duration, and an increase of the developed
      tension. With S2 > 30 V/cm, a marked delay in repolarization of the S2-induced
      action potential was followed by oscillation of membrane potential, resulting in
      repetitive spontaneous activity and often refractoriness to S1 stimulation. The
      aftereffects were independent of the phase of S2 application. Most of the
      aftereffects were preserved in the presence of nifedipine (1 microM) or ryanodine
      (1 microM). Only sodium channel blockade by tetrodotoxin (10 microM) modified the
      aftereffects by depressing the generation of spontaneous activity. These findings
      suggest that strong shocks (> 15 V/cm) will produce abnormal arrhythmogenic
      responses probably through a transient rupture of sarcolemmal membrane
      (electroporation) leading to a disturbance of the ionic equilibrium of the
      myocyte.

PMID- 7519408
TI  - Comparison of methods for removal of ectopy in measurement of heart rate
      variability.
AB  - Heart rate variability (HRV) analysis uses variations in heart rate to assess
      activity of the autonomic nervous system. Ectopic beats can affect HRV by
      introducing mathematical artifact into the computations of time- and frequency
      domain measures. Exclusion of ectopy-containing segments of data from analysis
      has been used to correct for ectopy, but this technique eliminates data and may
      bias HRV measurements if ectopic beats are causally associated with changes in
      autonomic tone. We have assessed algorithms for correcting for ectopy: deletion,
      in which ectopic beats are removed from the R-R sequence; linear and cubic spline
      interpolation; and nonlinear predictive interpolation, in which ectopy-free R-R
      sequences are used as templates for replacing ectopic beats. The null method (no
      ectopy correction) was evaluated to determine the importance of ectopy
      correction. These methods were applied to computer-generated sequences created by
      adding simulated ventricular premature depolarizations to 5-min ectopy-free R-R
      sequences. The null method resulted in significant alterations in HRV. Deletion
      and nonlinear predictive interpolation performed superiorly to linear or cubic
      spline interpolation, which overestimated low-frequency power and underestimated
      high-frequency power. Thus ectopy correction is necessary for HRV analysis;
      deletion of ectopic beats performs as well as or better than more complicated
      methods for these relatively short data samples.

PMID- 7519409
TI  - Dynamic arterial baroreflex in rabbits with heart failure induced by rapid
      pacing.
AB  - Excessive sympathetic nerve activity in heart failure could be attributable to
      impaired arterial baroreflex function. Employing transfer function analysis, we
      evaluated the arterial baroreflex in control rabbits (n = 8) and in rabbits with
      rapid pacing-induced heart failure (n = 10) in a dynamic manner. Rabbits in the
      heart-failure group showed elevated filling pressures, depressed first derivative
      of left ventricular pressure, pulmonary congestion, and an increased level of
      plasma norepinephrine. Varying aortic pressure pseudorandomly and recording
      responses in renal nerve activity, we calculated the transfer function from
      aortic pressure to renal nerve activity. The gain of the transfer function was
      similar between control and heart-failure rabbits over 0.04-0.4 Hz as well as the
      phase and the coherence, indicating that the dynamic arterial baroreflex was
      preserved in our rabbit heart-failure model. Vagotomy increased the gain of the
      arterial baroreflex over 0.04-0.4 Hz in control (P < 0.05) but not in heart
      failure rabbits, indicating that vagal afferents, which normally inhibit the
      dynamic arterial baroreflex, no more did so in heart failure. We conclude that
      excessive sympathetic nerve activity in heart failure may not be due to impaired
      dynamic arterial baroreflex, but that this apparently preserved arterial
      baroreflex in heart failure may be due to impaired cardiopulmonary baroreflex.

PMID- 7519410
TI  - SIN-1 reverses attenuation of hypercapnic cerebrovasodilation by nitric oxide
      synthase inhibitors.
AB  - We sought to determine whether the attenuation of the hypercapnic
      cerebrovasodilation associated with inhibition of nitric oxide synthase (NOS) can
      be reversed by exogenous NO. Rats were anesthetized (halothane) and ventilated.
      Neocortical cerebral blood flow (CBF) was monitored by a laser-Doppler probe. The
      NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg iv) reduced
      resting CBF [-36 +/- 5% (SE); P < 0.01, analysis of variance] and attenuated the
      increase in CBF elicited by hypercapnia (partial pressure of CO2 = 50-60 mmHg) by
      66% (P < 0.01). L-NAME reduced forebrain NOS catalytic activity by 64 +/- 3% (n =
      10; P < 0.001). After L-NAME, intracarotid infusion of the NO donor 3
      morpholinosydnonimine (SIN-1; n = 6) increased resting CBF and reestablished the
      CBF increase elicited by hypercapnia (P > 0.05 from before L-NAME). Similarly,
      infusion of the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-bromo-cGMP
      (n = 6) reversed the L-NAME-induced attenuation of the hypercapnic
      cerebrovasodilation. The NO-independent vasodilator papaverine (n = 6) increased
      resting CBF but did not reverse the attenuation of the CO2 response. SIN-1 did
      not affect the attenuation of the CO2 response induced by indomethacin (n = 6).
      The observation that NO donors reverse the L-NAME-induced attenuation of the CO2
      response suggests that a basal level of NO is required for the vasodilation to
      occur. The findings are consistent with the hypothesis that NO is not the final
      mediator of smooth muscle relaxation in hypercapnia.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7519412
TI  - Systemic and regional hemodynamics after nitric oxide synthase inhibition: role
      of a neurogenic mechanism.
AB  - The study tested the hypothesis that the increase in blood pressure and decrease
      in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro
      L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic
      mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control
      blood pressure was measured for 30 min. Cardiac output and tissue flows were
      measured with radioactive microspheres. All measurements of pressure and flows
      were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of
      control animals and in a second group of animals in which the autonomic nervous
      system was blocked by 20 mg/kg hexamethonium. In this group of animals, an
      intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain
      normal blood pressure. L-NAME treatment resulted in a significant increase in
      mean arterial pressure in both groups. L-NAME treatment decreased cardiac output
      approximately 50% in both the intact and autonomic blocked animals (P < 0.05).
      Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a
      significant decrease in renal, hepatic artery, stomach, intestinal, and
      testicular blood flow in both groups. These results demonstrate that the increase
      in blood pressure and decreases in cardiac output and tissue flows after L-NAME
      treatment are not dependent on a neurogenic mechanism.

PMID- 7519411
TI  - Somnogenic effects of rabbit and recombinant human interferons in rabbits.
AB  - Interferons (IFNs) are antiviral cytokines that possess several central nervous
      system activities. IFN therapy is associated with sleepiness, and the IFNs
      expressed during viral infection may be involved in the excess sleep associated
      with these infections. Most viruses stimulate the production of both IFN-alpha
      and IFN-beta. Although large doses of human IFN-alpha 2 are somnogenic in
      rabbits, the effects of species-specific IFNs on sleep in the rabbit have not
      been documented. We compared the somnogenic and antiviral effects of IFNs derived
      from rabbits to the effects of recombinant human (rh) IFN-alpha and IFN-beta.
      When injected intracerebroventricularly, rhIFN-alpha A/D, rabbit IFN-alpha/beta,
      and rabbit reference IFN induced non-rapid-eye-movement sleep and fever in a dose
      dependent manner. However, the doses of rabbit IFNs required to induce sleep were
      much lower than those of human IFNs. Heat treatment of both rabbit IFNs and human
      IFNs greatly reduced their in vitro antiviral effects. The in vivo activities of
      rabbit IFNs and rhIFN-alpha A/D were significantly attenuated after heat
      treatment. However, rhIFN-beta retained its sleep-promoting action after heat
      treatment, suggesting that microbial contaminants were responsible for its
      somnogenic and pyrogenic activities. We conclude that IFN-alpha is somnogenic.

PMID- 7519413
TI  - Symbolization in psychotherapy with patients who are disabled.
AB  - Symbols created during the process of psychotherapy serve psychological functions
      of giving form and substance to previously murky experiences, making what is
      private something shared, and forging meaningful linkages among thoughts,
      emotions, and perceptions. Symbols can also enable therapist and patient together
      to gain insight into transference themes, transformations in identity, and
      feelings about life changes, as well as serve as guides to articulating treatment
      goals. Clinical vignettes are used to illustrate the process.

PMID- 7519414
TI  - [Immune conflict pregnancy caused by allosensitization to minor erythrocytic
      rhesus determinants].

PMID- 7519415
TI  - SSPE and interferon.

PMID- 7519416
TI  - Plasma sialic acid and acute-phase proteins in patients with myocardial
      infarction.
AB  - Plasma total sialic acid (TSA) and lipid-associated sialic acid (LASA) were
      measured in 19 patients with a myocardial infarction (MI) on days 1, 2, and 5 and
      in 19 normal subjects. On each day plasma TSA was elevated in the MI patients as
      compared with that of normal subjects, although no significant difference was
      seen in the plasma LASA between the two groups. The following plasma acute-phase
      proteins were also assayed in the MI patients and the normal subjects: C-reactive
      protein (CRP), alpha-1 acid glycoprotein (AGP), alpha-1 antichymotrypsin (ACT),
      alpha-2 macroglobulin (AMG), and fibrinogen (FIB). Significantly elevated plasma
      concentrations were found in the MI patients as compared with normal subjects.
      Furthermore, a significant correlation was found between some of these plasma
      acute-phase proteins (ACT, AMG, and FIB) and plasma TSA in the MI patients and
      also in normal subjects (ACT, AMG, CRP, and FIB). However, no significant
      difference was noted in any of the plasma acute-phase proteins, or plasma TSA, or
      plasma LASA between survivors and patients who died of their MI.

PMID- 7519417
TI  - Antrectomy. A safe and effective bypass for unresectable pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is most often diagnosed too late for curative
      resection. Operative therapy, therefore, involves relief of biliary obstruction
      and relief or prevention of gastric outlet obstruction. Previous studies show
      that gastrojejunostomy done either therapeutically or prophylactically often
      causes delayed gastric emptying. OBJECTIVE: To describe the results of antrectomy
      with Billroth II reconstruction (A/BII) as the palliative operation for gastric
      outlet obstruction. SUBJECTS: Fifty patients with unresectable pancreatic cancer
      underwent A/BII without vagotomy from 1987 through 1993. Of these patients, 42
      underwent simultaneous biliary bypass; six had undergone biliary bypass from 3
      weeks to 34 months previously; and two with cancer originating in the uncinate
      process had no biliary bypass. RESULTS: One 87-year-old patient died on day 12 of
      azotemia and pulmonary insufficiency. The other 49 patients were discharged
      tolerating an oral diet an average of 11.3 days (range, 5 to 29 days) after
      A/BII. The length of stay following A/BII was not related to the extent of
      disease or to preoperative weight loss but was increased in older patients.
      CONCLUSION: The A/BII is a safe and effective bypass in patients with
      unresectable pancreatic cancer.

PMID- 7519418
TI  - Hyperbilirubinemia without common bile duct abnormalities and hyperamylasemia
      without pancreatitis in patients with gallbladder disease.
AB  - OBJECTIVE: To determine the incidence of jaundice and hyperamylasemia in the
      absence of common bile duct abnormalities or clinical pancreatitis in patients
      undergoing cholecystectomy. DESIGN: A continuous, prospective analysis of a
      consecutive case series was performed on all patients undergoing cholecystectomy.
      SETTING: An urban, tertiary care university hospital. PATIENTS: Adult patients
      with gallbladder disease. INTERVENTION: All patients underwent cholecystectomy.
      MAIN OUTCOME MEASURES: The presence or absence of common bile duct abnormalities
      was evaluated by cholangiography, and pancreatitis was identified by clinical
      signs, imaging studies, and direct visual inspection during cholecystectomy.
      RESULTS: All patients (N = 1746) undergoing cholecystectomy were prospectively
      categorized as having chronic calculous (n = 1410), acute calculous (n = 217),
      chronic acalculous (n = 70), or acute acalculous (n = 49) gallbladder disease. It
      was uncommon for patients with chronic calculous cholecystitis to have an
      elevated bilirubin level with no choledocholithiasis and a normal common bile
      duct or to have hyperamylasemia without pancreatitis. Twenty-five percent of the
      patients with acute calculous cholecystitis had a serum bilirubin level between
      34 and 86 mumol/L (2.0 and 5.0 mg/dL) with no common bile duct abnormality and 4%
      had hyperamylasemia without pancreatitis. Over one third of the patients with
      acute acalculous cholecystitis had an elevated bilirubin level with a normal
      common bile duct or an elevated amylase level without pancreatitis. CONCLUSION:
      Jaundice and hyperamylasemia can be produced by gallbladder disease alone.

PMID- 7519419
TI  - Dexamethasone inhibits the expression of an inducible nitric oxide synthase in
      infarcted rabbit myocardium.
AB  - Infarcted areas of rabbit myocardium show relatively higher inducible nitric
      oxide synthase activity, measured by the conversion of L-[14C]arginine to L
      [14C]citrulline. The principal finding in this study is that dexamethasone (2
      mg/kg) prevents the induction of inducible nitric oxide synthase in heart muscle
      when given before, or even 3 hr after coronary artery ligation. Additionally
      cyclic GMP levels remain unchanged following treatment with dexamethasone. It is
      possible that the enhanced production of nitric oxide by inducible nitric oxide
      synthase accounts, at least in part, for the depression of myocardial
      contractility seen in myocardial infarction and in other clinical conditions.

PMID- 7519420
TI  - Channel formation in planar lipid bilayers by a neurotoxic fragment of the beta
      amyloid peptide.
AB  - Alzheimer's disease (AD) pathology is characterized by plaques, tangles, and
      neuronal cell loss. The main constituent of plaques is beta-amyloid peptide (A
      beta), a 39-42 residue peptide which has been linked to disruption of calcium
      homeostasis and neurotoxicity in vitro. We demonstrate that a neurotoxic fragment
      of A beta, A beta (25-35) spontaneously inserted into planar lipid membranes to
      form weakly selective, voltage dependent, ion-permeable channels. We suggest that
      channel formation may be involved in the pathogenesis of AD and that A beta (25
      35) may be the active channel forming segment.

PMID- 7519421
TI  - Phosphorylation and activation of mitogen-activated protein kinase by kainic acid
      induced seizure in rat hippocampus.
AB  - Injection of kainic acid into rat induced a limbic seizure and increased the
      activities of two protein kinases with Mrs of 42 kDa and 44 kDa in the
      hippocampus. These two protein kinases were identified as MAP kinases by an anti
      MAP kinase antibody. These MAP kinases were phosphorylated at least at a tyrosine
      residue. The time course of the MAP kinase activation was roughly parallel with
      that of the seizure. These results indicate that the kainic acid-induced seizure
      induces MAP kinase activation in rat hippocampus.

PMID- 7519422
TI  - Transcriptional activation of the IL-6 response element in the junB promoter is
      mediated by multiple Stat family proteins.
AB  - IL-6 signals activate an IL-6 response element in the junB promoter, JRE-IL6, in
      a Ras-independent manner. IL-6 rapidly induced a DNA-binding activity to the Ets
      binding site of JRE-IL6 (JEBS), one of necessary DNA motifs of the IL-6 response
      element. The IL-6-induced JEBS-binding activity was indistinguishable from those
      to acute phase response element (APRE) in both kinetics of induction and its DNA
      binding specificity. Purified APRE binding factors (APRFs) from IL-6-stimulated
      rat liver were found to be composed of multiple Stat3-related proteins and Stat1.
      Moreover the purified APRFs specifically made a complex with JRE-IL6 with the
      same mobility as that observed in the crude extracts. These results indicate that
      an immediate early signal of IL-6 leading to activation of JRE-IL6 is mediated by
      STAT family transcription factors.

PMID- 7519423
TI  - Limited modulation of the mitogen-activated protein kinase pathway by cyclic AMP
      in rat parotid acinar cells.
AB  - Treatment of rat parotid acinar cells, in vitro, with agents that elevate
      intracellular cAMP had only limited impact on the ability of EGF to subsequently
      stimulate MAP-kinase activity or phosphorylation. A time course of cAMP
      accumulation following in vivo administration of isoproterenol showed the
      greatest level of cAMP 15 min following the primary injection. Over a 72 hr
      injection regimen, agonist-stimulated cAMP levels were gradually reduced to
      control levels while cAMP-dependent protein kinase A (PKA) activity in
      immunoprecipitates of Raf-1 or MAP-kinase remained elevated. Raf-1 did not
      undergo phosphorylation following incubation with the catalytic subunit of PKA,
      suggesting that in normal rat acinar cells proliferation induced by isoproterenol
      or EGF involves the p21ras-Raf-MAP-kinase signaling cascade despite the presence
      of cAMP.

PMID- 7519424
TI  - Fourth isoform of preprotachykinin messenger RNA encoding for substance P in the
      rat intestine.
AB  - Three different isoforms of preprotachykinin mRNA (PPT mRNA) encode for substance
      P and related neuropeptides (1). Here we report a fourth isoform of PPT mRNA
      which is generated by alternative exclusion of exon-7 and exon-6 from the PPT
      mRNA. It was present mainly in ileal smooth muscle and mucosa, colon, heart and
      brain and low level of this mRNA was detected in the jejunal smooth muscle and
      mucosa. This was not detected in the kidney or uterus. The level of this PPT mRNA
      was enhanced significantly by 60% during colitis in rat induced by trinitro
      benzene sulphonic acid.

PMID- 7519426
TI  - Pregnancy after cardiac transplantation.
AB  - A 39-year-old gravida 3, para 1102 underwent heart transplantation in 1990 for
      end-stage ischemic cardiomyopathy. She was immunosuppressed with FK506 and
      experienced no episodes of rejection or infection. She conceived in 1992 and her
      pregnancy was complicated by preeclampsia at 33 weeks' gestation. She delivered a
      2093 g female infant with mild and transient neonatal complications. This
      patient's pregnancy course and successful outcome is consistent with other
      reported cases.

PMID- 7519425
TI  - Interleukin-1 beta induces differential adhesiveness on human endothelial cell
      surfaces.
AB  - The adhesive strength between HL-60 and endothelial cells activated with IL-1
      beta was investigated according to the region (area) on the endothelial cell
      surface where the HL-60 cell was attached (nuclear, junctional, or cytoplasmic).
      Using a micropipette single-cell manipulation system, we demonstrated that the
      increase of adhesive force was due to the activation of the endothelial cell with
      IL-1 beta and a function of the region of the endothelial cell. The increase in
      adhesion strength due to the increased expression of E-Selectin on the
      endothelial cell was studied by the addition of monoclonal antibodies against E
      Selectin, ICAM-1, VCAM, and PECAM-1. Our findings suggest that the greatest
      adhesive strength was seen in the junctional region where the antibodies could
      not block the adhesion. However, the contribution of E-Selectin was significant
      in the nuclear region.

PMID- 7519427
TI  - Maternal serum alpha-fetoprotein levels in chorioangiomas.
AB  - It has been suggested that chorioangiomas should be added to the list of causes
      of elevated maternal serum alpha-fetoprotein levels. We undertook a review of
      maternal serum alpha-fetoprotein levels in chorioangiomas histologically
      diagnosed in our department, and a review of the literature. Maternal serum alpha
      fetoprotein level was elevated in only 1 of our 11 cases of chorioangioma. To
      date, there have been 14 case reports of chorioangiomas in which maternal serum
      alpha-fetoprotein levels have been recorded; 12 of these were associated with
      elevated maternal serum alpha-fetoprotein levels. We consider that, although
      chorioangiomas may be a cause of elevated maternal serum alpha-fetoprotein
      levels, it is likely to be infrequently a cause of such elevations in our
      population.

PMID- 7519428
TI  - Synthesis and antithyroid activity of 1,4,5-trialkyl 2-thioimidazole derivatives.
AB  - A series of compounds based on the structure of MTI (1-methyl-2-thioimidazole)
      were synthesized by condensation of alpha-hydroxyketones and alkylthioureas. The
      alpha-hydroxyketones were obtained by a radical reaction in the presence of
      sodium and the alkyl ester, while the alkylthioureas were prepared by
      nucleophilic addition of ammonia on an alkylisothiocyanate. The antithyroid
      activity of the 13 compounds prepared was evaluated in vitro by determination of
      the concentrations which led to a 50% inhibition (IC50) of the activity of
      thyroid peroxidase, and in vivo by assay of thyroid hormones levels and
      histological examination of the thyroid gland in rats treated chronically with
      the compounds. 1-methyl-4,5-dipropyl 2-thioimidazole (compound 10) was found to
      have the highest antithyroid activity of the 13 compounds synthesized.

PMID- 7519429
TI  - [Selective determination of different types of gastrointestinal mucins:use of
      histochemical reagents].
AB  - A method, transposed from the mucin histochemical stainings, was proposed to
      evaluate neutral, acidic and sulphated mucins by spectrocolorimetry. Stainings
      used were periodic acid/Schiff (PAS), Alcian blue (AB) pH 2.5, and Alcian blue
      (AB) pH 0.5. Mucin samples were extracted from mucosal scrapings, from intestinal
      contents of germ-free rats or from commercial pig gastric mucin. A mucin-enriched
      fraction was obtained and lyophilised and the protein content was determined.
      Each mucin type was spectrophotometrically analysed after staining and
      precipitation by slightly modified Carnoy fixative. The histochemical stainings
      used here, after modification by Carnoy fixative treatment, were, as shown by
      electrophoretic controls, specific for mucin types contained in these mucins
      without protein contaminant interference.

PMID- 7519430
TI  - Distribution of DNA, nuclear micro-heterogeneities and compaction of the
      chromatin in rabbit epididymal spermatozoa. Ultrastructural evaluation of the
      Feulgen-like technique using osmium ammine.
AB  - An adaptation of the Feulgen procedure to visualise DNA at the ultrastructural
      level, using osmium ammine instead of Schiff reagent, was applied to ultrathin
      sections of rabbit epididymal spermatozoa, known to display increasing chromatin
      compaction as they progress through the epididymis. In contrast with the somatic
      cell nuclei of the epididymal epithelium, which display classical staining, the
      chromatin of spermatozoa is partly or fully destroyed during the hydrolysis step
      of the technique. The sperm chromatin resistance towards destruction is a
      function of the initial sperm nuclear compaction and of the duration of
      hydrolysis prior to Feulgen-like staining. For a given nucleus, the maximum
      staining intensity is only obtained after an optimal duration of hydrolysis.
      However, because of this duration and local differences in chromatin compaction,
      the total DNA of a section is never completely visualized. The most compact parts
      of the nuclei are not yet stained, when the less compact parts have already been
      destroyed. This gives rise to a sperm-specific pattern which corresponds to the
      enhancement of microheterogeneities present in all sperm nuclei and to the local
      depolymerisation of the nuclear material during hydrolysis. The depolymerised
      parts of nuclei sit over the sections, and they also bind uranyl acetate,
      ethidium bromide and anti-protamine antibodies. Therefore, in sperm nuclei, the
      Feulgen-like staining at the ultrastructural level does not reveal the true DNA
      distribution. However, the amount of staining can be quantified to evaluate sperm
      chromatin compaction.

PMID- 7519431
TI  - Separation of a 170-K delayed-implantation-associated protein with inhibitory
      activity on trophoblast outgrowth and RNA synthesis by mouse embryo.
AB  - PROBLEM: To screen the uterine protein responsible for embryonic dormancy
      associated with delayed implantation. METHOD: Uterine protein extracts and sera
      from mice in which delayed implantation had been induced and those from pregnant
      mice were separated by three steps of chromatography and SDS-PAGE by monitoring
      an inhibitory activity on trophoblast outgrowth. The presence of the separated
      protein in the uterine luminal fluid was assessed. Effect of the protein on cell
      proliferation and RNA synthesis by blastocysts were assessed. RESULTS: A 170-K
      protein was found in the uterine tissue as well as uterine luminal fluid
      associated with delayed implantation. The 170-K protein suppressed RNA synthesis
      by approximately 50% and cell proliferation in blastocysts. CONCLUSION: A 170-K
      protein is secreted into the uterine lumen during delayed implantation period.
      The ability of 170-K protein to suppress RNA synthesis and cell proliferation may
      play a role in regulation of embryonic dormancy associated with delayed
      implantation.

PMID- 7519432
TI  - Evidence for presence of hyaluronan binding protein on spermatozoa and its
      possible involvement in sperm function.
AB  - Hyaluronic acid, a major component of the extracellular matrix, plays an
      important role in the regulation of different cellular processes, e.g.,
      locomotion, cell-cell interaction during morphogenesis, and differentiation.
      Distribution of hyaluronic acid with respect to the role of sperm hyaluronidase
      in sperm penetration and gamete interaction is well established. In order to
      elucidate this mechanism, in our current study we have identified and
      demonstrated, for the first time, the presence of a 68-kDa cell surface
      hyaluronic acid binding glycoprotein (HABP) in spermatozoa of different species
      (rat, mice, bull, and human) by immunoblot analysis and indirect
      immunofluorescence using the polyclonal antibodies raised against purified HABP.
      Furthermore, we were able to demonstrate a differential distribution of 68-kDa HA
      binding protein on the sperm head, midpiece, and tail of different species. To
      identify its role in sperm function, we observed its declining pattern during
      epididymal maturation and also the inhibition of sperm-oolemmal adherence by
      pretreatment of the sperms with anti-HABP antibodies. We have further observed
      its in vivo phosphorylation in motile spermatozoa. All our data clearly indicate
      that sperm hyaluronan binding protein may have a specific role in sperm
      maturation, motility, and fertilization processes.

PMID- 7519433
TI  - Role of alveolar macrophage-T cell adherence in accessory cell function in human
      immunodeficiency virus-infected individuals.
AB  - Previous work has shown that alveolar macrophages (AM) from human
      immunodeficiency virus (HIV)-infected patients are superior accessory cells (AC)
      and secrete greater amounts of T cell-stimulatory cytokines than do normal AM. We
      now examine the role of AM-T cell adherence in AM AC function by examining the
      ability of beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) to
      block adherence and lymphoproliferation. Mitogen-induced (concanavalin A,
      pokeweed mitogen) adhesion and proliferation were studied in the presence and
      absence of mAb directed against beta 2 integrins and ICAM-1. AM from normal
      subjects and HIV-positive patients were used as AC, and normal T cells were used
      as responders. Normal and HIV AM bound equal numbers of T cells under similar
      conditions. Adherence was blocked by antibodies to beta 2 integrins and ICAM-1 in
      both groups. Con A-induced lymphoproliferation was positively correlated with
      adherence in normal volunteers. In contrast, greater Con A-induced AM-T cell
      adherence in HIV-positive patients was associated with worse AC function.
      Antibodies that impaired AM-T cell adherence completely inhibited AC function in
      both groups when added at the beginning of mitogen assays, indicating that
      initial contact was required. However, the addition of antibodies after 4 h
      inhibited lymphoproliferation less in HIV-infected individuals than in normal
      volunteers, suggesting that prolonged AM-T cell adherence was less important for
      optimal AC function in these patients. Using these and previous results, we
      present a model for AM AC function in normal volunteers and HIV-infected
      individuals.

PMID- 7519436
TI  - Role of the sympathetic nervous system in hypertension and benign prostatic
      hyperplasia.
AB  - Hypertension and benign prostatic hyperplasia (BPH) have a number of features in
      common. For example, both occur with increasing frequency in the elderly, and
      both are a major source of health expenditure worldwide. However, the most
      striking feature linking hypertension and BPH is the aetiological role of the
      sympathetic nervous system. Sympathetic tone mediated by the alpha-receptor is
      vital in the control of blood pressure. By selectively inhibiting the alpha 1
      adrenoceptors in the vasculature, thereby inhibiting the response to epinephrine
      and norepinephrine and thus reducing peripheral resistance, selective alpha 1
      inhibitors such as doxazosin produce a physiological reduction in blood pressure.
      Receptors of the alpha 1 subtype are also found in the prostate, the urethra and
      bladder neck. Doxazosin, by reducing the tone of the prostatic smooth muscle, has
      the potential to improve urinary flow rate, as well as the obstructive and
      irritative symptoms characteristic of BPH.

PMID- 7519437
TI  - Epidemiology of benign prostatic hyperplasia: risk factors and concomitance with
      hypertension.
AB  - Benign prostatic hyperplasia (BPH) is a common condition. Eighty-eight per cent
      of autopsy specimens from men aged over 80 years have been shown to have
      histological BPH. It is the cause of the commonest surgical procedure in older
      men (3 men in 10 may ultimately undergo prostatectomy). Despite its being such a
      common occurrence, little is known with any certainty about the epidemiology of
      BPH. The incidence, even the population prevalence, is difficult to determine for
      a variety of reasons. Knowledge of risk factors is sparse, and analytical
      epidemiological studies of BPH are difficult to conduct. Case-control studies are
      problematic, in that a control group may be difficult to define and a large
      proportion of the control group may have undiagnosed BPH. There have been reports
      of associations between BPH and hypertension, but there is no consistent
      suggestion that such an association could be causal. However, given the frequent
      occurrence of both conditions in ageing men, a large proportion of men may well
      have both diseases. With the increase in the number of men now reaching older
      ages it is clear that BPH, as well as hypertension, will continue to have a
      substantial and increasing influence in terms of morbidity, mortality and
      healthcare costs. The need for high-quality epidemiological information and
      consequent increased prospects for prevention is obvious.

PMID- 7519434
TI  - Constitutive expression of inducible nitric oxide synthase in human bronchial
      epithelial cells induces c-fos and stimulates the cGMP pathway.
AB  - Two major roles have been defined for nitric oxide (NO): cell-cell communication
      mediated by the stimulation of cyclic guanosine 3',5'-monophosphate (cGMP)
      synthesis and cytotoxicity by direct or indirect interaction of the free radical
      NO with cellular targets. Thus, pathologic states might result from an alteration
      of NO pathways, e.g., by deregulated activity of NO synthase. To investigate this
      hypothesis, we introduced the murine-inducible NO synthase (iNOS) sequence into
      immortalized human bronchial epithelial cells (BEAS-2B). iNOS activity, measured
      by conversion of [14C]arginine to [14C]citrulline in the presence of 1 mM EGTA,
      was higher than 100 pmol/min/mg protein in early passages of iNOS-transfected
      cells but decreased with cell subculturing. No iNOS activity could be detected in
      control vector-transfected cells. NO stimulated cGMP production in iNOS
      transfected cells, and this effect was inhibited by the iNOS inhibitor NG
      monomethyl-L-arginine. In addition, NO production induced c-fos expression and
      did not interfere with clonal cell growth. These results suggest that BEAS-2B
      cells constitute a suitable model to study the consequences of iNOS activity on
      signal transduction pathways in bronchial epithelium.

PMID- 7519435
TI  - Production of nitric oxide by rat type II pneumocytes: increased expression of
      inducible nitric oxide synthase following inhalation of a pulmonary irritant.
AB  - Nitric oxide is a highly reactive molecule that has been implicated in host
      defense and tissue injury. In the present studies, we determined whether rat type
      II alveolar epithelial cells have the capacity to produce this mediator. We found
      that type II cells synthesize significant quantities of nitric oxide after
      treatment with the inflammatory cytokines, interferon-gamma (IFN-gamma) and/or
      interleukin-1 beta (IL-1 beta), or with the combination of IFN-gamma and tumor
      necrosis factor-alpha. In contrast to rat alveolar macrophages, type II cells
      were unresponsive to lipopolysaccharide. Production of nitric oxide by type II
      cells in response to IFN-gamma was dose dependent, reaching a maximum at 100
      U/ml, and blocked by NG-monomethyl-L-arginine (L-NMA), a nitric oxide synthase
      inhibitor. Northern blot analysis demonstrated that nitric oxide production by
      type II cells was due to expression of mRNA for an inducible form of nitric oxide
      synthase (iNOS). Following brief exposure of rats to irritant-inducing doses of
      ozone (2 ppm, 3 h), type II cells were found to produce significantly more nitric
      oxide than were cells from control animals. This was due to increased expression
      of iNOS mRNA. Cells from ozone-treated rats were also sensitized to produce more
      nitric oxide in response to IFN-gamma and IL-1 beta. This was associated with a
      marked increase in expression of iNOS mRNA and enzyme protein in the cells. We
      also found that ozone inhalation caused enhanced production of hydrogen peroxide,
      as well as spontaneous and IFN-gamma-induced cytostasis of type II cells toward
      P815 mouse mastocytoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519438
TI  - Profile of doxazosin in the hypertensive man with benign prostatic hyperplasia.
AB  - A number of studies have confirmed the beneficial effects of selective alpha 1
      adrenoceptor inhibitors in patients with benign prostatic hyperplasia (BPH). Most
      produce clinically significant improvements in symptom scores and uroflow,
      although some of the shorter-acting agents often do so at the expense of adverse
      events. Doxazosin has a slower onset of action and longer plasma half-life than
      any other available selective alpha 1-adrenoceptor inhibitor, which may confer
      advantages in terms of tolerability over the more rapidly absorbed and eliminated
      selective alpha 1-adrenoceptor inhibitors. Doxazosin produces statistically
      significant increases in mean and maximum uroflow, as well as small but
      significant reductions in maximum voiding pressures and statistically significant
      improvements in symptoms of frequency, urgency, nocturia, reduced uroflow and
      sensation of incomplete emptying. Changes in uroflow and symptoms are similar in
      normotensive and hypertensive patients with BPH, and are accompanied in
      hypertensive patients by a statistically significant fall in blood pressure.
      Treatment is well tolerated in both normotensive and hypertensive patients.
      Doxazosin, by virtue of its unique pharmacological profile, is a valuable new
      treatment option for the many patients with mild to moderate bladder outflow
      obstruction due to BPH. It may be especially appropriate therapy for those
      considerable numbers of elderly men who have both hypertension and bladder
      outflow obstruction due to prostatic enlargement.

PMID- 7519439
TI  - Comparison of testosterone metabolism in benign prostatic hyperplasia and human
      prostate cancer cell lines in vitro.
AB  - Pathways of testosterone metabolism in tissue slices and cell suspensions of
      human benign hyperplastic prostate (BPH) tissue and human prostate cancer cell
      lines (DU145, HPC-36M, PC-3/MA2 and LNCaP) were investigated. Thin layer
      chromatography analysis was used to identify the following tritiated metabolites:
      testosterone, 5 alpha-dihydrostestosterone (DHT), 5 alpha-androstane-3 alpha/3
      beta-17 beta-diol (androstanediols), 4-androstene-3,17-dione (androstenedione)
      and 5 alpha-androstanedione. The predominant pathway for testosterone metabolism
      in BPH was via 5 alpha-reductase producing 5 alpha-dihydrotestosterone (71% and
      75% total metabolites in slices and suspensions incubated for 24 h,
      respectively). The cancer cell lines DU145 and HPC-36M resembled BPH by
      metabolizing testosterone predominantly to DHT (68% and 82% total metabolites,
      respectively), although the rate of metabolism was much lower in the cell lines
      (0.099 and 0.05 pmol testosterone/mg protein/h in DU145 and HPC-36M) compared to
      the BPH cell suspensions (6.4 pmol testosterone/mg protein/h). In contrast, PC
      3/MA2 contained high 17 beta-HSD activity forming large amounts of 4-androstene
      3,17-dione (84% total metabolites), converting testosterone at a rate faster
      (12.8 pmol testosterone/mg protein/h) than the BPH cell suspensions. LNCaP
      rapidly converted testosterone exclusively to a glucuronide conjugate (7.4 pmol
      testosterone/mg protein/h), although after incubation with [3H]-4-androstene-3,17
      dione, 5 alpha-reductase activity was demonstrated. LNCaP was the only cell line
      whose growth and colony-forming ability was stimulated by testosterone and DHT.
      BPH and all the cell lines tested had 5 alpha-reductase activity, but only the
      prostate tissue and the cell lines DU145 and HPC-36M converted testosterone
      predominantly to DHT.

PMID- 7519440
TI  - Hepatic regeneration in vitamin A-deficient rats: changes in the expression of
      transforming growth factor alpha/epidermal growth factor receptor and retinoic
      acid receptors alpha and beta.
AB  - We have studied the effect of vitamin A deficiency on the expression of
      transforming growth factor alpha (TGF-alpha), hepatocyte growth factor, acidic
      fibroblast growth factor, and TGF-beta 1 after partial hepatectomy of vitamin A
      supplemented and vitamin A-deficient rats. In addition, the expressions of
      epidermal growth factor receptor and retinoic acid receptors alpha (RAR alpha)
      and beta (RAR beta) were studied. Partial hepatectomy was performed on the
      animals from the vitamin A-supplemented and -deficient groups at the age of 10
      weeks when the weights of the animals on the deficient diet had reached a
      plateau. Two animals from each group were sacrificed before the operation and
      also 12, 24, 48, and 72 h and 5 days after the operation. Partial hepatectomy of
      the vitamin A-deficient rats leads to a focal necrosis of liver followed by a
      rapid restoration of liver mass. Expression of the TGF-alpha and epidermal growth
      factor receptor was highly elevated in the livers of deficient animals after
      partial hepatectomy. In the vitamin A-supplemented animals, the level of
      epidermal growth factor receptor was down-regulated following partial
      hepatectomy. Proliferation of oval cells in vitamin A-deficient livers following
      partial hepatectomy and subsequent increase in 2.1-kilobase alpha-fetoprotein
      mRNA was observed, suggesting an activation of the stem cell compartment. Another
      unexpected result was an inverse relationship between RAR beta and RAR alpha
      expression, the latter becoming the major species after partial hepatectomy in
      animals on the vitamin A-deficient regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519441
TI  - Effect of target structure on cross-linking by psoralen-derivatized
      oligonucleoside methylphosphonates.
AB  - A series of psoralen-derivatized oligodeoxyribonucleoside methylphosphonates were
      examined for their abilities to cross-link to DNA and RNA oligonucleotide
      targets. These targets were designed to have either a random coil or a hairpin
      structure in solution. The methylphosphonate oligomers cross-linked with
      approximately the same rates to the random coil DNA and RNA targets, although the
      extent of cross-linking to the DNA target was higher than that to the RNA target.
      For a given methylphosphonate sequence, cross-linking decreased as the
      temperature increased, and this behavior paralleled the interaction of the
      oligomer with the target as determined by ultraviolet melting experiments. The
      oligomers also cross-linked efficiently with the DNA hairpin target, but little
      or no cross-linking was observed with the RNA hairpin. In the case of these
      hairpin targets, the extent of cross-linking was dependent upon the location of
      the oligomer binding site relative to the stem and loop regions of the hairpin.
      The lack of reactivity with the RNA hairpin may be due to the high stability of
      the stem of this target versus that in the DNA target and the relatively lower
      efficiency of binding of the methylphosphonates to RNA versus DNA targets. The
      sequences of the oligomers are complementary to vesicular stomatitis virus M
      protein mRNA. One of the oligomers was tested, and was found to cross-link at 20
      degrees C to VSV N-mRNA to approximately the same extent as observed for cross
      linking with the random coil RNA target, suggesting that the mRNA binding site
      for the oligomer most likely is in a somewhat open conformation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7519442
TI  - Effects of arabinosylcytosine-substituted DNA on DNA/RNA hybrid stability and
      transcription by T7 RNA polymerase.
AB  - Cytosine arabinoside (araC) is a potent antileukemic agent which interferes with
      DNA replication both as a dNTP competitive inhibitor as well as after its
      misincorporation into DNA. We previously developed a chemical methodology for the
      synthesis of DNA oligomers containing araC which allowed us to study its site
      specific effects on duplex stability and chemical reactivity [Beardsley, G. P.,
      Mikita, T., Klaus, M., & Nussbaum, A. (1988) Nucleic Acids Res. 16, 9165], as
      well as its effects on DNA ligase and DNA polymerase activity [Mikita, T., &
      Beardsley, G. P. (1988) Biochemistry 27, 4698]. The DNA polymerase studies, in
      addition to other observations, showed that araC in DNA templates could have an
      inhibitory effect on polymerase bypass. As a template lesion, there exists the
      potential for interference with other aspects of DNA metabolism, such as
      transcription. We have characterized a DNA/RNA hybrid containing an araC-G base
      pair, comparing thermal stability, chemical cleavage rates, and duplex gel
      mobility to an identically sequenced DNA duplex. We find that the A-form DNA/RNA
      hybrid and the B-form DNA duplex are nearly identical in the extent their thermal
      stability is affected by an araC-G(dG) base pair. Substitutions of araC for dC
      were made at various positions in a series of DNA duplex substrates containing a
      T7 RNA polymerase promoter with variable length coding strands. These were used
      to probe the effect of araC on promoter recognition, initiation, and elongation
      by T7 RNA polymerase in vitro. Substitutions in the central promoter region had
      no observable effect on RNA polymerase binding, initiation rate, or
      transcriptional output. Coding strand substitutions defined an area of high
      sensitivity in the initiation region where miss-starts, primer slippage, and an
      inability to escape from abortive cycling occur depending on the position
      substituted. Substitutions after position 10 had little effect on transcription
      output. These highly variable, position dependent effects indicate a narrow
      window of vulnerability where transcription output is severely reduced
      (approximately 100-fold) by a subtle DNA lesion that has little or no consequence
      when situated elsewhere in these small coding units.

PMID- 7519443
TI  - Structural characterization and alternate splicing of the gene encoding the
      preadipocyte EGF-like protein pref-1.
AB  - Preadipocyte factor 1 (pref-1), a member of the EGF-like protein family, is a
      transmembrane protein with six tandem EGF-like repeats in the putative
      extracellular domain. Expression of pref-1 is abolished during the in vitro
      differentiation of 3T3-L1 preadipocytes to adipocytes, and constitutive
      expression of pref-1 in preadipocytes inhibits their differentiation [Smas, C.M.,
      & Sul, H.S. (1993) Cell 73, 725-734]. In the present studies, we have isolated
      and characterized genomic clones for pref-1 and have identified multiple pref-1
      transcripts generated by alternate splicing. The pref-1 gene consists of five
      exons and four introns spanning approximately 7.3 kb. By primer extension
      analysis, the transcription start site was determined to be 169 bp upstream from
      the translation initiation codon. We have identified functional promoter
      sequences by transient transfection using a 2.1 kb fragment of the pref-1 5'
      flanking region linked to a luciferase gene; the pref-1-luciferase fusion gene
      construct gave 20-fold higher promoter activity as compared to the promoterless
      vector. Analysis of exon-intron junctions reveals that unlike the majority of the
      mammalian EGF-like genes, EGF-like repeats of pref-1 are not encoded by discrete
      exons. Through RT-PCR and the isolation and analysis of multiple pref-1 cDNA
      clones, we have identified, in addition to full-length pref-1, five alternately
      spliced forms with various in-frame deletions of all or a part of the sixth EGF
      like repeat, juxta-membrane, and predicted transmembrane domains.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7519444
TI  - Cloning and characterization of the SmIMP25 integral membrane protein of the
      parasitic helminth Schistosoma mansoni.
AB  - The cDNA and genomic clones encoding a 25 kDa integral membrane protein, termed
      SmIMP25, were isolated from Schistosoma mansoni. The 2.2 kb SmIMP25 mRNA was
      found in all developmental stages of the parasite tested: miracidium, sporocyst,
      cercaria and adult worm. The SmIMP25 gene is at least 16 kb long and it is split
      by four introns ranging in size from 36 bp to > or = 9 kb. Excluding the introns,
      the gene and the cDNA show 100% sequence identity. The cDNA has an open reading
      frame encoding a protein 223 amino acids long. The predicted sequence reveals a
      distinct hydrophobic domain of 20 amino acids located 12 residues from the
      carboxyl-terminal end. The properties of this domain (marked hydrophobicity,
      size, flanking by charged residues and C-terminal location) are typical of the
      transmembrane segments of integral membrane proteins. The presence of three
      potential N-glycosylation sites is also consistent with membrane proteins that
      are often glycosylated at the extracellular domain. Accordingly we propose that
      SmIMP25 is an integral membrane protein in which residues 1-191 are
      extracellular, residues 192-211 comprise the hydrophobic domain that spans the
      membrane, and residues 212-223 are intracellular. The SmIMP25 was synthesized as
      a fusion protein in bacteria and antibodies were elicited in rabbits. Antibodies
      against SmIMP25 specifically precipitated a 25 kDa protein from cell-free
      products programmed by schistosome mRNA, in agreement with the size of the
      protein predicted from the cDNA sequence. Immunofluorescence studies showed
      SmIMP25 on the surface of the parasite. Surface molecules expressed at the host
      parasite interface are likely to provide information on host parasite
      relationship and may serve as targets for protective immunity.

PMID- 7519445
TI  - Molecular characterization of ovary trehalase of the silkworm, Bombyx mori and
      its transcriptional activation by diapause hormone.
AB  - We have isolated a cDNA encoding ovary trehalase of the silkworm, Bombyx mori.
      Sequence analyses revealed that the isolated cDNA contains 3143 nucleotides and
      comprises 579 amino acids, including a cleavable signal sequence and five
      potential N-glycosylation sites. Northern blot analysis showed a 3.0 kb
      transcript in developing ovaries carrying membrane-bound trehalase. A single copy
      of trehalase gene was present in the haploid genome of the silkworm. The effect
      of diapause hormone on the accumulation of trehalase mRNA was examined on
      developing ovaries in in vivo and in vitro conditions. The synthetic diapause
      hormone brought about a 6-fold increase in trehalase mRNA content in ovaries 4 h
      after injection. The similar increase was found in ovaries which were incubated
      in vitro with diapause hormone. Coincubation of ovaries with diapause hormone and
      actinomycin D could not increase the mRNA level in ovaries, and maintained a
      basal level which was found in ovaries incubated without diapause hormone. These
      results indicate that diapause hormone stimulates transcription of the trehalase
      gene in developing ovaries of the silkworm.

PMID- 7519448
TI  - cDNA cloning and expression of inducible nitric oxide synthase from rat vascular
      smooth muscle cells.
AB  - Nitric oxide (NO) is an important signal molecule. In blood vessels, nitric oxide
      produced by the endothelium modulates vascular tone by inducing cGMP formation in
      smooth muscle cells. The latter cell type does not express NO synthase normally
      but expression is induced by the cytokines, interferon-gamma, tumor necrosis
      factor, and interleukin-1. We have constructed a cDNA library from cytokine
      stimulated rat aortic smooth muscle cells and isolated a cDNA clone that contains
      the full-length sequence of inducible NO synthase. It is 4119 bp and confers NO
      synthesizing activity when transfected into COS-7 cells. The nucleotide sequence
      is 92% identical with inducible NO synthase of murine macrophages and contains a
      497 bp untranslated 3' sequence with five conserved A(U)nA motifs that may be
      important in the regulation of mRNA turnover. This is supported by the short half
      life (2.6 h) of smooth muscle NO synthase mRNA, which contrasts with brain and
      endothelial NO synthase.

PMID- 7519447
TI  - Organization of the bovine gene encoding the endothelial nitric oxide synthase.
AB  - The bovine endothelial nitric oxide synthase gene plus 2.9 kilobases of 5'
      flanking sequence has been isolated and characterized. The gene spans 20
      kilobases and contains 26 exons and 25 introns. Two transcription start sites
      have been determined by primer extension analysis which are located 170 and 240
      base pairs upstream, respectively, from the methionine translational initiation
      codon. Evidence supporting the upstream boundary region for transcriptional
      initiation was also obtained by reverse transcription-polymerase chain reaction.
      The 5'-flanking region lacks a typical TATA box but contains numerous putative
      transcription factor binding sites. These include consensus sequences for an AP-1
      site, an NF-1 site, a tumor necrosis factor responsive element, two sterol
      regulatory elements, 3 acute-phase response element, two sterol regulatory
      elements, 3 acute-phase response elements, 6 GATA motifs, 16 CACCC boxes, 5 Sp1
      sites, 15 estrogen half-palindromic motifs, and 9 fluid shear stress-responsive
      elements. The isolated gene promoter directs basal transcription of a luciferase
      reporter gene when transiently transfected into bovine aortic endothelial cells.
      High sequence homology of the promoter region to the human endothelial nitric
      oxide synthase gene promoter (75% nucleotide identity in 1.6 kilobases of 5'
      flanking sequence) suggests evolutionary conservation of transcriptional
      regulation. Isolation and characterization of the bovine endothelial nitric oxide
      synthase gene should facilitate further investigation of mechanisms by which gene
      expression is regulated.

PMID- 7519446
TI  - Isolation and characterization of two alternatively spliced complementary DNAs
      encoding a Xenopus laevis angiotensin II receptor.
AB  - We have isolated two cDNAs of 1.7 and 3.0 kb, produced by alternative splicing,
      that encode a angiotensin II (AII) receptor from a Xenopus laevis heart cDNA
      library. The two clones had identical coding regions with each other and were
      found to belong to the G protein-coupled receptor superfamily like the mammalian
      type 1 AII receptors (AT1); their amino acid sequence was 68.7% homologous with
      the human AT1 receptor sequence. However, there was a 1.3 kb insertion at the 3'
      untranslated region of the longer clone. The insertion contained 9 repeats of an
      ATTTA motif, suggesting that the two mRNAs undergo distinct post-transcriptional
      regulation by virtue of a difference in their stability. Although the Xenopus
      receptor exhibited distinct specificities for AII receptor antagonists compared
      with mammalian AII receptors, several common characteristics, including the
      effect of dithiothreitol and guanosine 5'-O-(3-thiotriphosphate), demonstrated
      that the cloned receptor is a counterpart of the mammalian AT1 receptor.
      Moreover, the cloned receptor was expressed most abundantly in the Xenopus heart,
      which is inconsistent with the tissue distribution of mammalian AII receptors.
      This indicated that the Xenopus heart, unlike that of mammals, plays a major role
      in the AII-dependent regulation of blood pressure and extracellular fluid volume.

PMID- 7519449
TI  - Sequence and structure of the RNA subunit of RNase P from the cyanobacterium
      Pseudoanabaena sp. PCC6903.
AB  - The catalytic RNA subunit of ribonuclease P (RNase P) from the cyanobacterium
      Pseudoanabaena sp. PCC6903 has been cloned and sequenced. The RNA has a primary
      and secondary structure with overall similarity to other cyanobacterial RNase P
      RNAs characterized so far but contains some peculiarities of its own. A consensus
      promoter sequence can be identified at the 5' end of the gene.

PMID- 7519450
TI  - [Wall stents for treatment of malignant ureteral obstruction].
AB  - Self-expanding metallic stents (Wallstents) were implanted in 44 ureters in 31
      patients suffering from malignant ureteral obstruction. The causes of obstruction
      were lymph node metastases or primary tumors of the pelvis. During the first 4
      weeks, reversible thickening of the mucosa occurred. After 4 to 6 weeks, the
      stents were incorporated into the wall of the ureter. In a follow-up period from
      1 to 27 months, tumor-associated hydronephrosis was prevented in all patients by
      implantation of the Wallstents.

PMID- 7519451
TI  - Direct in vivo gene transfer and expression in malignant cells using adenovirus
      vectors.
AB  - To evaluate the ability of replication-deficient, recombinant adenovirus vectors
      to transfer genes to human tumor cells in vivo, adenovirus vectors containing the
      Escherichia coli lacZ (Ad.RSV beta gal) gene (coding for beta-galactosidase; used
      as a cell marker for gene transfer) or the human alpha 1-antitrypsin (Ad-alpha
      1AT) cDNA (used as an example of a secreted protein) were administered
      intraperitoneally to nude mice with human malignant mesothelioma cell (H-MESO-1)
      malignant ascites. Preliminary in vitro studies showed that both vectors
      effectively transferred genes to H-MESO-1 cells. Tumor cells recovered from
      ascites of animals intraperitoneally administered a control adenovirus revealed
      no evidence of beta-galactosidase (beta-gal) activity 3 or 14 days later. In
      contrast, beta-gal activity was detected at the same time points in tumor cells
      from animals receiving intraperitoneal Ad.RSV beta gal. Flow cytometric
      quantification of beta-gal activity in recovered cells showed < 3% beta-gal
      positive cells in animals administered control virus, but in animals administered
      intraperitoneal Ad.RSV beta gal there was a mean of 71 +/- 18% positive cells at
      3 days and 56 +/- 27% at 14 days. Human alpha 1AT was not detected by enzyme
      linked immunosorbent assay (ELISA) in ascites of animals receiving a control
      virus; however, in ascites of animals administered Ad-alpha 1AT, 21,000 +/- 3,800
      ng/ml of human alpha 1AT was detected at 3 days and 4,900 +/- 1,700 ng/ml at 14
      days. These data demonstrate that replication-deficient recombinant adenovirus
      vectors can be used to transfer genes to malignant cells in vivo and suggest a
      new strategy for genetic modification for antitumor therapy.

PMID- 7519452
TI  - Gene therapy of cystic fibrosis lung disease using E1 deleted adenoviruses: a
      phase I trial.

PMID- 7519454
TI  - Pilocarpine-induced salivary secretion, kinin system and nitric oxide in rats.
AB  - In anaesthetized rats, intraperitoneal injection of pilocarpine (0.1 to 1 mg.Kg
      1) induced a dose-dependent flow of saliva. During salivation by pilocarpine (0.5
      mg.Kg-1), the blood content of submaxillary glands was not significantly
      increased but the blood volume of the animals was reduced. The salivary flow rate
      induced by pilocarpine was similar in normal and kininogen-deficient rats. L-NG
      nitro-arginine (L-NOARG, 35 mg.Kg-1), a nitric oxide synthesis inhibitor,
      increased the salivary flow elicited by pilocarpine (0.5 mg.Kg-1). L-NOARG did
      not modify the blood volume loss but decreased the blood content of the
      submaxillary glands. The volume of salivary secretion induced by isoproterenol
      (250 mg.Kg-1) was lower in kininogen-deficient rats than in normal rats. It was
      significantly reduced by HOE 140 (2 mg.Kg-1), a bradykinin antagonist. L-NOARG
      increased the salivary flow induced by isoproterenol during the ten first minutes
      of collection but suppressed it thereafter. We concluded that kinins are not
      involved in the stimulating effect of pilocarpine on rat salivary glands but
      these peptides would participate to the development of the salivation induced by
      isoproterenol in rats. Nitric oxide contributes to the control of the vascular
      tone in rat salivary glands. The influence of L-NOARG on salivation would be
      explained by its effects on blood pressure and vascular resistances.

PMID- 7519453
TI  - Ligation of CD28 on resting T cells by its ligand B7 results in the induction of
      both Th1- and Th2-type cytokines.
AB  - It has been well documented that cross-linking CD28 with mAb can provide a potent
      costimulatory signal to T cells for the production of IL-2, IL-6, IFN-gamma, GM
      CSF and TNF-alpha. Much less is known about the role of the CD28 molecule in the
      induction of Th2-type lymphokines such as IL-4, IL-5, and IL-10. So far, only
      limited data are available about the secretion of IL-2, IL-6, IFN-gamma, and GM
      CSF by T cells when using B7 as the natural ligand for CD28. We investigated
      whether B7-CD28 ligation can result in the secretion of Th2-type cytokines using
      3T6 mouse fibroblasts transfected with human CD32 (Fc gamma RIIa high-responder
      allele, 3T6-CD32 cells) or with both CD32 and B7 (3T6-CD32/B7 cells). It was
      found that upon stimulation through the TCR/CD3 complex, B7-CD28 interaction not
      only results in the production of cytokines of the Th1 type, but also gives rise
      to the production of large amounts of Th-2 type cytokines such as IL-4 and IL-10.
      In contrast to the production of IL-2, IFN-gamma, GM-CSF, and TNF-alpha, the
      production of IL-4 after co-stimulation with B7-CD28 interaction was restricted
      to CD45RO+ memory T cells. In addition, the production of IL-4 after co
      stimulation by B7-CD28 interaction was not influenced by the addition of IFN
      gamma. The production of IFN-gamma was not affected by IL-4, but was slightly
      inhibited by IL-10.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519456
TI  - Effects of a restricted diet on in vitro spontaneous activity and glucose
      metabolism in isolated rat uterus. Influence of castration.
AB  - The effects of a restricted-diet (50% of the normal intake during 25 d) on the
      isometric developed tension (IDT), the metabolism of labelled glucose, and the
      levels of glycogen, of uteri isolated from ovariectomized (25 d) and non
      ovariectomized rats were explored. The restriction of food intake produced a fall
      in the contractile activity of normal, non-ovariectomized, rats in permanent
      diestrous compared to normally fed rats in diestrous. On the contrary, in
      castrated rats, the IDT of isolated uterus from underfed rats, was significantly
      higher than its normal-fed controls. In normal rats the formation of 14CO2 from U
      14C-glucose was significantly lower in uterine preparations from restricted-diet
      animals than the control one. On the other hand, in castrated rats, the formation
      of 14CO2 increased as a result of underfeeding. The post-incubation levels of
      glycogen in uteri from normal-fed animals diminished significantly in comparison
      to 0 time values. In uteri from rats subjected to a dietary restriction, the
      initial glycogen values were lower than in normal-fed controls, but they did not
      decline further after incubation in KRB medium. On the contrary, even when the
      levels of glycogen were significantly lower at 0 time than in diestrous animals,
      they diminished in ovariectomized rats after incubation, no matter the diet. The
      above results indicate that the effects of restricted-diet on contractile
      activity, levels of glycogen and glucose metabolism were not observed in
      ovariectomized rats. Further researches are needed to clarify that point.

PMID- 7519455
TI  - Variations in the activity of some metabolic enzymes during development of
      Artemia parthenogenetica (Crustacea: Anostraca).
AB  - Metabolic activity of the cysts as well as other developmental stages of Artemia
      parthenogenetica was determined by studying various key metabolic enzymes such as
      lactate dehydrogenase (LDH) and malate dehydrogenase (MDH). The electrophoretic
      studies on LDH show the existence of a single fraction uniformly in all the
      developmental stages of A. parthenogenetica. Electrophoretic patterns of MDH
      during the same stages show variations in isozymic fractions as development
      proceeds towards adults. Enzyme assay during lactate oxidation and pyruvate
      reduction of LDH as well as malate oxidation and oxaloacetate reduction of MDH in
      different developmental stages reveals that the anaerobic metabolism is more
      prevalent than the aerobic type. Further quantification of these enzymes shows
      that their activities are low and stable in the encysted gastrulae, and increase
      rapidly when the embryo emerges. One of the kinetic properties such as pH has
      impact on the general behavior of the enzymes throughout the developmental
      stages.

PMID- 7519457
TI  - Systemic bone growth factors in light breed mares and their foals.
AB  - There is a high incidence of bony pathology in race horses. Thus, plasma GH, IGF
      1, osteocalcin (OC), calcium (Ca) and inorganic phosphorus (P) concentrations
      were measured in 12 healthy Selle Francais foals and their dams during the first
      five months after birth. Plasma IGF-1 and OC concentrations were higher in foals
      than in mares (336 +/- 25 vs 230 +/- 18 ng/ml, P < 0.05; 52.5 +/- 3.2 vs 4.9 +/-
      0.1 ng/mg, P < 0.01, respectively). A significant positive linear relationship
      could be established between these two parameters in foals (IGF-1 = 19 + 0.619
      OC; P < 0.05). Another striking evidence was the increase in plasma IGF-1, OC and
      P concentrations observed during the first week of postnatal life. IGF-1, OC, P
      and Ca concentrations remained elevated during the experimental period,
      indicating an intense skeletal growth (confirmed by growth curve) in these
      animals.

PMID- 7519458
TI  - Changes in liver drug glucuronidation during cholestasis are non predictable.
AB  - Liver microsomal glucuronidation of acetaminophen, chloramphenicol, salicylic
      acid, lorazepam, p-nitrophenol and morphine were measured in 8 days bile duct
      ligated rats. Compared to normals, cholestatic rats showed a decrease of 31% for
      p-nitrophenol glucuronidation; salicylic acid glucuronidation increased 281%;
      acetaminophen glucuronidation increased 38% while morphine, chloramphenicol and
      lorazepam values were similar to controls. We concluded that cholestasis produces
      non predictable changes on liver drug glucuronidation pathways.

PMID- 7519459
TI  - Effects of oxfenicine on the atria from fed and fasted rats.
AB  - The aim of the investigation was to assess whether endogenous triacylglycerol
      contributes to the maintenance of the atrial functions. To attain this
      information, the atria from fed and fasted rats were treated with oxfenicine
      which is a cardioselective inhibitor of carnitine palmitoyltransferase I. In the
      presence of glucose, oxfenicine suppressed lipolysis without affecting the
      pacemaker and contractile activities. When exposed to 2-deoxyglucose in a
      substrate-free medium, the atria displayed a progressive fall of the contractile
      strength and pacemaker rate. The dysfunctions appeared faster in the atria from
      fed rats coinciding with a smaller triacylglycerol mobilization. Under this
      condition, oxfenicine abolished the triacylglycerol breakdown, increased the fall
      in the peak tension, elicited a rise in the resting tension and accelerated the
      decline of the pacemaker rate, leading in a significant number of atria to a
      complete cessation of the spontaneous contractions. These effects proceeded
      faster in the fed rats atria. Present data suggest that glucose oxidation is
      sufficient to meet the atrial energy demand when the fatty acid catabolism is
      impeded. The noxious effects of oxfenicine, attained after the glucose metabolism
      was eliminated, lend direct evidence to the notion that endogenous
      triacylglycerol supports, at least partly, the atrial functions.

PMID- 7519460
TI  - Ventricular electrophysiological properties in normal and congenitally
      hypothyroid neonatal rats.
AB  - The serum thyroid hormone levels [total (TT3) and free (FT3) triiodothyronine]
      and the heart rates were determined in neonatal rats of different ages (1-5-10
      days). Thyroid hormone levels increase gradually in the first 10 days of age. The
      heart rate, tested at a body temperature of 37 degrees C, also increases during
      the same period. As the increase in heart rate in this phase of rat life is not
      due to the catecholamines, it is suggested that such an increase might depend on
      the increased thyroid hormone activity. On the other hand in congenitally
      hypothyroid rats the levels of both hormones and heart rates are lower than in
      normal animals of the same age. The electrophysiological properties of
      ventricular muscle fibres include a longer action potential, irrespective of
      stimulation frequency, in younger, naturally hypothyroid animals. The duration of
      action potential is greater in the congenitally hypothyroid animals, at all ages.
      These data demonstrate that, as in young and adult rats, the age-related
      modifications in heart rate, found in neonatal rats, might be due to thyroid
      dependent modifications of cardiac electrophysiology.

PMID- 7519461
TI  - Biochemical attempt to characterize thirteen cichlid species by their muscular
      parvalbumins.
AB  - This paper shows the usefulness of polyacrylamide gel electrophoresis (PAGE)
      separation of a few well-characterized muscle proteins, the parvalbumins, in the
      systematic study of 13 cichlid species. The separation of the isoforms of these
      abundant, quite species-specific fish parvalbumins is fast, easy, and requires
      but small quantities of muscle material. Used alone, this technique suggests
      hypotheses for species classification. In conjunction with morphological
      analysis, it makes it possible to confirm or invalidate doubts about the
      determination.

PMID- 7519462
TI  - Kallikrein, nitric oxide and the vascular responses of the submaxillary glands in
      rats exposed to heat.
AB  - During exposure of normal rats to an ambient temperature of 36 degrees C or 40
      degrees C, body temperature increases; thermolytic processes are set up and
      saliva is spread on the skin. In Wistar rats, thermolytic salivation started when
      body temperature was above 39 degrees C. This water loss was associated with a
      loss of body weight. A 10% reduction of plasma volume was observed in animals
      exposed to 40 degrees C but no change was observed in those exposed to 36 degrees
      C. Body weight loss was reduced by hexamethonium, atropine, prazosin, HOE 140, a
      bradykinin-antagonist, and NG-nitro-L-arginine (NOARG), a NO synthase inhibitor.
      The weight and blood content of the submaxillary glands, which are the main
      effectors of the thermolytic processes, increased as a function of the ambient
      temperature. The increase of blood content was enhanced by hexamethonium but
      reduced by atropine and NOARG. The weight increase was inhibited by
      hexamethonium, prazosin, HOE 140 and NOARG. At an ambient temperature of 40
      degrees C, a large swelling developed around the submaxillary glands, resulting
      in a distention of the surrounding soft tissues. This local oedema fluid
      contained low levels of endogenous proteins but accumulated exogenous labelled
      albumin. This swelling was enhanced by atropine but decreased by hexamethonium,
      trasylol, HOE 140, NOARG, ketoprofen, a cyclooxygenase inhibitor, and prazosin.
      In kininogen deficient rats, the blood content of submaxillary glands increased
      as a function of ambient temperature. No increase in glandular weight and no
      swelling of the of the soft tissues were observed. After atropine, the weight of
      the glands increased and a swelling of the soft tissues appeared.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7519463
TI  - Regional myocardial efficiency is improved in experimental aorto-caval shunt.
AB  - We determined whether regional myocardial work efficiency (segment work/regional
      O2 consumption) would be elevated by surgically-augmented inflow. In 10
      anesthetized open-chest dogs, shunt between the ascending aorta and the superior
      vena cava was used to increase cardiac output. Hetastarch (15 ml/kg) was infused
      before opening the shunt to maintain coronary perfusion pressure. Regional
      myocardial segment work and O2 consumption (MVO2) were measured, during control
      and two levels of elevated flow. Regional segment work (g.mm/min) was calculated
      as the integrated products of force (g - miniature transducer) and segment
      shortening (mm - ultrasonic dimension gauge) during an averaged beat expressed
      per minute. Local MVO2 (ml O2/min/100g) was calculated from regional blood flow
      (microspheres) and O2 saturations (microspectrophotometry). It was found that
      regional myocardial segment work increased significantly (P < 0.05) from 926 +/-
      94 to 1656 +/- 220 to 1479 +/- 309 (g.mm/min) for closed, half-open, and open
      shunt. This increase was primarily associated with increased segment shortening
      (from 147 +/- 14.1 to 204.4 +/- 20.1 to 232 +/- 26.1 mm/min). Both force
      development and regional MVO2 were unchanged during the experiment. Regional
      myocardial efficiency was significantly elevated during shunt function (from 95
      +/- 12 to 187 +/- 31 to 213 +/- 57 g.mm/ml O2/100g). Systolic ejection stiffness
      (defined as the slope of the force-length relationship during the period of
      ejection) decreased from 8.0 +/- 0.9 to 4.7 +/- 0.4 to 4.5 +/- 0.9 g/mm during
      elevated inflow. It is concluded that when cardiac work is augmented primarily by
      segment shortening, regional myocardial efficiency is improved. This improvement
      is associated with decreased resistance to shortening (stiffness).

PMID- 7519464
TI  - Electrophysiological properties of the hyperthyroid rat heart.
AB  - We have studied the effects of in vivo administration of different T3 doses to
      thyroidectomized rats on electrophysiological properties, measured in vitro, of
      papillary muscle fibers. The treatment with increasing T3 doses was associated
      with a significant reduction of the action potential duration up to a dose as
      large as 25 micrograms/100 g body weight every second day. The treatment with
      larger doses of T3 tended to restore the values of the action potential duration
      present in animals treated with physiological doses (5 micrograms/100 g body
      weight every second day). Action potential duration is frequency dependent. As
      the stimulation rate was increased from 1 to 5 Hz, this duration increased in all
      groups. However the difference between the rat groups remained significant. The
      cardiac frequency measured in unanaesthetized rats increased as the T3 doses.
      Furthermore the intrinsic frequency showed a similar increase, indicating a
      direct effect of T3 on the pacemaker cells in all thyroid states. The mechanism
      of this action of the thyroid hormone is not, however clear.

PMID- 7519465
TI  - [Atrial natriuretic factor: retrospective and perspectives].
AB  - Since the hypotensive and natriuretic properties of crude cardiac extracts were
      first demonstrated in 1981 in the rat, the effector molecule has been isolated,
      purified and synthesized. The hormonal factor is produced by atrial myocytes in
      mammals and stored as a prohormone. Secretion mainly results from a volemic
      stress inducing an atrial stretch. Secretion includes a maturation step. A
      peptide of 28 amino-acids (ANP) is then released into the bloodstream. ANP has a
      half-life of a few minutes. ANP binds to specific receptors expressed at the
      target cell surface. B-receptors mediate the biological actions of ANP by an
      increase in cGMP while C-receptors are involved in clearance of the peptide. The
      kidney as well as the cardiovascular and endocrine systems are the main target
      sites for ANP. The renal effects of ANP are expressed by an enhanced diuresis and
      natriuresis which may result from an increased glomerular filtration rate and/or
      a reduced tubular reabsorption of salt and water. Renal hemodynamics may also be
      modified due to a renal specific vasodilator effect of ANP. The reduction of
      systemic blood pressure may result from changes in cardiac output and/or in
      peripheral vascular resistance. Several neurohumoral interactions of ANP also
      contribute to sustain the cardiovascular and renal effects described above. In
      view of these properties, ANP is of particular interest in order to understand
      the homeostasis of salt and water under physiological as well as or
      physiopathological conditions. In this regard, therapeutic prospects are
      intensively investigated. Finally, evolutionary perspectives are actually
      considered from studies in lower vertebrates.

PMID- 7519466
TI  - Involution of rat thymus: characterization of cytoplasmic glucocorticoid
      receptors, evidence of glucocorticoid resistant dexamethasone receptor-positive
      cells.
AB  - In rats, thymic relative weight increased after birth reaching maximum values
      between days 15-30 and then decreased markedly in a similar way in both sexes,
      while the organ's absolute weight continued to increase until days 80-90 and
      declined slowly with apparent sex differences from day 30 onward. Scatchard
      analysis revealed that the [3H] dexamethasone (Dexa) receptor sites concentration
      showed a pattern comparable to that found in relative thymic weight, with no
      change in the apparent KD. The reduction of lymphocytes mitotic activity
      resulting in reduction of immature thymocytes production must be accompanied by a
      fall of the number of glycocorticoid receptors in ageing thymuses. Despite the
      profound decrease in the glucocorticoid receptor sites levels, the thymus
      sensitivity to Dexa remained unchanged during development. Indeed, in prepuberal
      and adult rats, the steroid administration was followed 4 days after by a
      transient thymic weight loss of about 70-80% which was mainly linked to the
      reduction in the cortical area. In contrast, the density of [3H] Dexa binding
      sites was reduced unexpectedly by 25% only after steroid treatment. These
      findings provided evidence that Dexa receptor-positive population cells in thymus
      was formed in a large part by relatively glucocorticoid resistant cells.

PMID- 7519467
TI  - [Correction of disorders of cardiac electric stability in post-infarction
      cardiosclerosis using a diet enriched with polyunsaturated fatty acids].
AB  - In a 14-20 days after feeding of rats with "eikonole" (cod-liver oil, deduced
      from skeletal muscle and enriched by eicosapentaenic and docosahexaenic fatty
      acids). Myocardial infarction by Selie has been induced and in a 30 days of the
      same feeding, contractile function and heart electrical stability in situ have
      been investigated. Eikonole increased heart fibrillation threshold by 50%,
      decreased the frequency of spontaneous extrasystole in 3 times and ectopic
      activation (extrasystole), induced by n. vagus stimulation, in 2.5 times.
      Eikonole increased the intensity of structures' functioning in the state of
      relative physiological rest, but did not influence essentially on pressure and
      the velocity of myocardial contraction and weakening.

PMID- 7519468
TI  - [Effect of nifedipine and ruthenium red on the contractile function and oxidative
      metabolism of the myocardium].
AB  - The role of intra- and extracellular calcium in beta-adrenergic regulation of
      rat's heart have been shown. It was found that oxidative metabolism of resistant
      and non-resistant animals to hypoxia is under control of 2 different
      intracellular calcium pools. The role of intracellular calcium is more important
      in non-resistant to hypoxia rats.

PMID- 7519470
TI  - [Identification of the M. tuberculosis-M. bovis complex using the polymerase
      chain reaction].
AB  - High-specific and sensitive method of identification of mycobacteria human and
      bovine species by using PCR was created. The pair of primers from DNA sequence,
      coding protein MbaA was chosen. As a target for amplification was taken the
      sequence of DNA from 1796 to 2115 pb coding region of protein from 407 to 514
      amino acid with lesser hydrophobicity index. That gave the possibility to choose
      the specific for M. tuberculosis--M. bovis part of DNA. Simple and effective
      method of preparing mycobacterial cells for DNA amplification was proposed.

PMID- 7519469
TI  - [Influence of "sessile"immune receptors of lymphocyte membranes on their
      cholinoreceptors in mice immunized with various antigens].
AB  - Influence of macromolecular agents (some agents) on cholinoreceptors' activity of
      lymphocytes' membranes and their ability to bind with acetylcholine and it's
      analogues (carbacholine and others) has been investigated. This work presents the
      materials to problem of receptors' interaction and express one of the
      immunopharmacological characteristics of "receptor-receptor" system.

PMID- 7519471
TI  - Differentiation-linked changes in tyrosine phosphorylation, functional activity,
      and gene expression downstream from the granulocyte-macrophage colony-stimulating
      factor receptor.
AB  - The HL-60 model of myeloid maturation was used to test whether changes in
      signaling from the granulocyte-macrophage colony-stimulating factor (GM-CSF)
      receptor accompany maturation-related changes in cellular responses to GM-CSF.
      Receptor expression, tyrosine phosphorylation, functional activity, and c-fos
      gene expression were measured. Functional GM-CSF receptors were present
      throughout differentiation as both uninduced and dimethyl sulfoxide (DMSO)
      induced HL-60 cells responded to GM-CSF, albeit in different ways. Uninduced
      promyelocytes proliferated in response to GM-CSF, whereas DMSO-induced cells lost
      the capacity to proliferate but did respond with increased expression of beta 2
      integrins, enhanced respiratory burst activity, and metabolism of arachidonic
      acid. GM-CSF-stimulated upregulation of c-fos mRNA expression was not detected in
      immature cells but developed after 2 to 4 days with DMSO in line with a marked
      increase in responsiveness to stimulation with phorbol ester, showing that
      increased expression of c-fos is predominantly a feature of mature phagocytes. GM
      CSF stimulated the tyrosine phosphorylation of a broadly similar range of
      proteins in both uninduced and DMSO-treated HL-60 cells, but protein bands were
      more heavily phosphorylated in DMSO-induced cells. Phosphorylation was rapid in
      onset and very transient in immature cells. Phosphorylation of several proteins,
      in particular a 130-kD band, was more sustained in DMSO-induced cells. These
      differences in signaling were not because of numerical differences in receptors,
      because reduction of GM-CSF concentration to trigger equivalent numbers of high
      affinity receptors delayed the onset of phosphorylation in DMSO-induced cells. We
      conclude that there are maturation-related changes in signaling downstream from
      the GM-CSF receptor.

PMID- 7519472
TI  - Transcription factor GATA-2 is expressed in erythroid, early myeloid, and CD34+
      human leukemia-derived cell lines.
AB  - To understand the functional roles that the GATA factors may play during
      hematopoietic cell differentiation, we examined the expression of GATA factor
      mRNAs and protein products in various human cell lines. Blot hybridization
      analyses demonstrated that GATA-1 and GATA-2 mRNAs are expressed abundantly in a
      set of cell lines established from human myelogenous leukemia cells, but the
      expression pattern of each factor is distinct. GATA-2 mRNA is expressed in all
      cell lines tested that express erythroid markers, and, in addition, the mRNA is
      also expressed in three CD34+ cell lines and two early myeloid cell lines. In
      contrast, the expression of GATA-1 mRNA showed tight correlation to that of the
      erythroid/megakaryocytic lineage markers. We also found that the GATA-2 probe
      identifies two types of mRNA. Structural analysis of genomic DNA clones encoding
      human GATA-2 coupled with RNA blot analysis demonstrated that there exists an
      alternative use of polyadenylation consensus sequences in a single exon and this
      causes the molecular heterogeneity among GATA-2 mRNAs. Through immunochemical and
      immunohistochemical analyses using anti-GATA-1- and anti-GATA-2-specific
      antibodies, GATA-2 protein was clearly shown to be present in the nuclei of
      leukemia-derived early myeloid and CD34+ cell lines, whereas both GATA-1 and GATA
      2 proteins are expressed in erythroid/megakaryocytic cell lines. Thus, the
      expression profile of GATA-2 is consistent with the hypothesis that GATA-2 plays
      unique roles for the transcriptional activation of genes in cells at an early
      stage of hematopoietic differentiation and in developing cells of the erythroid
      and myeloid lineages.

PMID- 7519473
TI  - Growth and differentiation of the human megakaryoblastic cell line (ELF-153): a
      model for early stages of megakaryocytopoiesis.
AB  - ELF-153 is a cell line that has been established from a patient with a poorly
      differentiated acute myeloid leukemia associated with an acute myelofibrosis. A
      majority of cells had a blast morphology with the phenotype of a myeloid
      hematopoietic progenitor, ie, CD34+, CD33+, CD13+, HLA-DR+, but CD38-, and the
      remaining cells (5% to 10%) expressed platelet restricted proteins such as CD41,
      CD42, CD36, CD61, and von Willebrand factor; some of them were polyploid (up to
      32N) and exhibited demarcation membranes and alpha granules. No erythroid or
      other lineage-specific markers were detected. Proliferation of ELF-153 cells was
      highly stimulated by interleukin-3 (IL-3) and granulocyte-macrophage colony
      stimulating factor and to a lesser extent by stem cell factor and IL-6. In
      contrast, the cell line did not respond to erythropoietin, leukemia inhibitory
      factor, IL-7, IL-11, granulocyte colony-stimulating factor, and basic fibroblast
      growth factor. ELF-153 cells could be separated by flow cytometry into three
      discrete cell populations (CD34+/CD61-, CD34+/CD61+, and CD34-/CD61+) with
      different proliferative and endomitotic properties corresponding to distinct
      stages of the mega karyocyte (MK) differentiation. This MK differentiation, which
      involved a minority of ELF-153, could be increased in the presence of 5
      azacytidine and phorbol ester, but could not be significantly modified by growth
      factors. By contrast, cytochalasin B dramatically induced polyploidization
      without differentiation. It is noteworthy that association of 5-azacytidine to
      cytochalasin B dramatically induced the production of polyploid MK cells. To
      understand the molecular mechanisms underlying this MK differentiation, the
      expression of GATA-1 and GATA-2 was investigated in subpopulations of ELF-153. A
      high level of GATA-1 and GATA-2 mRNA was only present in the CD61+ cells.
      Therefore, these two transactivating factors may play an important role in the MK
      differentiation of ELF-153. We conclude that ELF-153 might be an important tool
      to investigate the mechanisms by which transcription factors control
      differentiation of MK progenitors.

PMID- 7519474
TI  - Clustering of vitronectin and RGD peptides on microspheres leads to engagement of
      integrins on the luminal aspect of endothelial cell membrane.
AB  - In previous work (Conforti et al, Blood 80:437, 1992), we have shown that
      integrins in endothelial cells (EC) are not polarized to the basal cell membrane,
      but are also exposed on the apical cell surface, in contact with blood.
      Therefore, endothelial integrins might be available for binding circulating
      plasma proteins. However soluble plasma vitronectin (vn) bound very poorly to EC
      apical surface and this interaction was unaffected by Arg-Gly-Asp (RGD) peptides
      or an anti-alpha v beta 3 serum. In contrast, beads (diameter, 4.5 microns)
      coupled with plasma vn associated to EC apical surface in a time- and
      concentration-dependent way. Addition of antibodies directed to vn, alpha v beta
      3, and RGD-containing peptides blocked the interaction of vn beads with EC. In
      contrast, heparin and antibodies directed to alpha v beta 5 and beta 1 integrin
      chain had no effect. Beads coupled with Gly-Arg-Gly-Asp-Ser-Pro bound to the EC
      surface, but not those coupled with Gly-Arg-Gly-Glu-Ser-Pro. This interaction was
      blocked by alpha v beta 3 antibodies and RGD peptides, but not by alpha v beta 5
      antibody. Overall, these results indicate that luminal alpha v beta 3 retains its
      binding capacity for surface-linked vn and RGD-containing ligands, but binding is
      observed only when the ligand is offered in a clustered, multivalent form. We
      propose that when vn or RGD-containing proteins are bound to circulating cells,
      they can act as bridging molecules by promoting adhesion of the cells to the
      endothelium via apical integrins.

PMID- 7519476
TI  - Maturation of acute T-lymphoblastic leukemia cells after CD2 ligation and
      subsequent treatment with interleukin-2.
AB  - In this study, we have investigated the ability of various cytokines to induce
      the maturation of acute lymphoblastic leukemia (T-ALL) cells with early T-cell
      phenotype. Leukemic blasts from 17 untreated T-ALL patients were assayed for
      their ability to acquire mature T-cell markers, CD3/T-cell receptor (TCR) in
      particular, after incubation with one or a combination of recombinant human
      interleukin-1 (IL-1), IL-2, IL-4, IL-7, and CD2-specific monoclonal antibody
      (MoAb). IL-7 or IL-2 induced the proliferation of some leukemic cells, whereas
      sequential cell treatment with CD2-MoAb and then IL-2 promoted CD3/TCR expression
      on nearly all CD2+ cells (15 of 16), except for 1 T-ALL that developed into CD3
      CD16+CD56+ cells. Differentiation of T-ALL cells was also evidenced through the
      downregulation of CD34 precursor cell antigen, the generation of CD4+ and CD8+
      cells from CD4+ CD8+ precursors, and the acquisition of mature T-cell functions.
      CD2 ligation induced a progressive increase of surface expression of IL-2
      receptor alpha (IL-2R alpha) and IL-2R beta and an accelerated in vitro death of
      leukemic cells. The ligation of IL-2R by IL-2 rescued T-ALL cells from death and
      promoted their progression toward more mature cells expressing extracellular
      CD3/TCR alpha beta complexes. Intracellular analysis indicates that TCR alpha
      transcription and membrane translocation of both TCR alpha and TCR beta were
      promoted in these conditions. Analysis of intracellular signals transduced during
      T-ALL differentiation indicated that CD2-ligation induced Ca2+ influx and that
      the ligation of CD2 and IL-2R induced distinct tyrosine phosphorylation patterns.
      The addition of inhibitors of tyrosine phosphorylation abolished T-ALL cell
      differentiation, which suggests the involvement of tyrosine kinases in this
      phenomenon. Together, we showed the constant maturation of leukemic early T cells
      after stimulation of surface CD2 and the high-affinity IL-2R.

PMID- 7519475
TI  - Expression and purification of functional recombinant epitopes for the platelet
      antigens, PlA1 and PlA2.
AB  - The platelet antigens, PlA1 and PlA2, are responsible for most cases of
      posttransfusion purpura (PTP) and neonatal alloimmune thrombocytopenia (NAIT) in
      the caucasian population and are determined by two allelic forms of the platelet
      glycoprotein GPIIIa gene. To study the interaction between these antigens and
      their respective antibodies, we inserted the sequence that encodes the signal
      peptide and the N-terminal 66 amino acids of the PlA1 form of GPIIIa into the
      expression vector pGEX1. To express the PlA2 antigen, nucleotide 196 of the PlA1
      coding sequence was mutated to the PlA2 allelic form. When transformed and
      induced in Escherichia coli, the two constructs produce glutathione S-transferase
      (GST)/N-terminal GPIIIa fusion proteins, one containing leucine at position 33
      (PlA1), the other proline (PlA2). These proteins are easily purified in milligram
      quantities using glutathione-Sepharose and react specifically with their
      respective antibodies by immunoblot and enzyme-linked immunosorbent assay.
      Antigenicity of the PlA1 fusion protein in reduced glutathione increases with
      time; moreover, the addition of oxidized glutathione accelerates this process,
      presumably because of formation of the native disulfide bonds. Neutralization
      assays indicate that the PlA1 fusion protein competes for all of the anti-PlA1
      antibody in the serum of patients with PTP and NAIT that is capable of
      interacting with the surface of intact platelets. This study shows that the GST/N
      terminal GPIIIa fusion proteins contain conformational epitopes that mimic those
      involved in alloimmunization, and that regions other than the amino terminal 66
      amino acids of GPIIIa are not likely to contain or be required for the
      development of functional PlA1 epitopes. Furthermore, these recombinant proteins
      can be used for the affinity-purification of clinical anti-PlA1 antibodies and
      specific antibody identification by western blotting, making them useful in the
      diagnosis of patients alloimmunized to PlA1 alloantigens.

PMID- 7519477
TI  - Differential expression of bcl-2 and susceptibility to anti-Fas-mediated cell
      death in peripheral blood lymphocytes, monocytes, and neutrophils.
AB  - The recently identified Fas antigen (Ag) is a cell surface molecule that can
      mediate apoptosis. The cytoplasmic product of proto-oncogene bcl-2 has been shown
      to prolong the cellular survival by inhibiting apoptosis. To elucidate the
      physiologic significance of expression of both molecules, we examined the
      expression of Fas Ag and bcl-2 on blood leukocyte populations and evaluated their
      sensitivity to the cytolytic action of anti-Fas antibody. Although Fas Ag was
      expressed on a fraction of lymphocytes, both neutrophils and monocytes expressed
      Fas Ag constitutively. In contrast, there was marked difference among these
      leukocytes regarding bcl-2 expression. Lymphocytes expressed bcl-2 intensely, but
      monocytes showed weaker bcl-2 expression, and neutrophils were essentially absent
      for bcl-2 expression. Seemingly reflecting this lack of bcl-2-expression,
      neutrophils more easily underwent apoptotic cell death in vitro as compared with
      monocytes and lymphocytes. We showed that anti-Fas antibody affectively
      accelerated apoptotic cell death in neutrophils. However, the apoptosis-inducing
      effect of anti-Fas antibody was minimal on monocytes, and lymphocytes were
      resistant to this antibody. These results suggest that anti-Fas-mediated cell
      death may, in part, be determined by bcl-2 expression status in Fas+ lymphoid and
      hematopoietic cells.

PMID- 7519478
TI  - High levels of the shed form of L-selectin are present in patients with acute
      leukemia and inhibit blast cell adhesion to activated endothelium.
AB  - L-selectin is expressed by most leukocytes and mediates the initial step of
      adhesion to vascular endothelium. A feature of this adhesion receptor is to be
      shed from the cell surface. We report here the presence of high levels of the
      shed form of L-selectin (sL-selectin) in plasma from patients with acute
      leukemia. We also show that sL-selectin purified from acute leukemia plasma
      exhibits functional activity. The mean (+/- 1 SD) plasma level of sL-selectin
      among 100 healthy individuals was 2.1 +/- 0.7 micrograms/mL. This value was
      increased (> 2 SD above the mean) in 63% of 58 patients with acute lymphoblastic
      leukemia (ALL) and 59% of 93 patients with acute myelogenous leukemia ([AML] P <
      .001). Repeated measurements in 24 patients showed normal-range levels in 16 of
      16 patients in complete remission and high levels in eight of eight patients with
      therapy-resistant acute leukemia or leukemia relapse. Furthermore, elevated sL
      selectin levels were detected in cerebrospinal fluid of three patients with ALL
      suffering from a relapse limited to the central nervous system. Epitope mapping
      with monoclonal antibodies demonstrated that L-selectin shedding from leukemic
      blasts was accompanied by conformational changes of its epidermal growth factor
      like domain. A functional role for sL-selectin purified from leukemic plasma was
      supported by its ability to completely inhibit L-selectin-dependent adhesion of
      blast cells to tumor necrosis factor-alpha (TNF-alpha)-activated endothelium in
      vitro. These results suggest that sL-selectin may have an important role in the
      regulation of leukemic cell adhesion to endothelium. In addition, monitoring of
      the sL-selectin level may be useful for evaluating leukemia activity, in
      particular for the detection of leukemia relapse.

PMID- 7519479
TI  - Contrasting effects of recombinant human granulocyte-macrophage colony
      stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood
      elements in childhood-onset cyclic neutropenia.
AB  - Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has
      been shown to increase average neutrophil counts substantially in patients with
      childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to
      eliminate the cyclic oscillations of neutrophil counts or those of other blood
      elements (monocytes, platelets, eosinophils, and reticulocytes) that are
      characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil
      counts are amplified during G-CSF treatment. We have compared the effects of
      recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three
      patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age).
      These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously)
      for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to
      document changes in the cyclic oscillations of blood neutrophils and other blood
      elements; two of the patients were subsequently treated with G-CSF (5.0
      micrograms/kg/d, subcutaneously) and observed for comparable periods of time.
      Unlike G-CSF treatment, which increased average neutrophil counts more than 20
      fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold,
      although eosinophilia of varying prominence was induced in each patient. However,
      at the same time, GM-CSF treatment dampened or eliminated the multilineage
      oscillations of circulating blood elements (neutrophils, monocytes, platelets,
      and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of
      the same patients markedly amplified the oscillations of neutrophil counts and
      caused the cycling of other blood elements (monocytes in particular) to become
      more distinct. These findings support the conclusion that the distinctive cycling
      of blood cell production in childhood-onset cyclic neutropenia results from
      abnormalities in the coordinate regulation of both GM-CSF-responsive,
      multipotential progenitor cells and G-CSF-responsive, lineage-restricted,
      neutrophil progenitors.

PMID- 7519482
TI  - Comparative subcellular distribution of the copper complexes of bleomycin-A2 and
      deglycobleomycin-A2.
AB  - We have compared the cellular uptake and subcellular localization of 14C-labeled
      bleomycin-A2 (BLM) and deglycobleomycin-A2 in living KB3 cells. Both drugs
      exhibit poor internalization into cells but reveal significantly different
      intracellular distribution, with low and high accumulation into the cell nuclei
      for BLM and deglyco-BLM, respectively. The results indicate that the carbohydrate
      chain does not constitute a limiting factor for BLM permeation and is directly
      implicated in the intracellular distribution of the drug into cells.

PMID- 7519481
TI  - The kit-ligand (steel factor) and its receptor c-kit/W: pleiotropic roles in
      gametogenesis and melanogenesis.
AB  - The c-kit receptor tyrosine kinase belongs to the PDGF/CSF-1/c-kit receptor
      subfamily. The kit-ligand, KL, also called steel factor, is synthesized from two
      alternatively spliced mRNAs as transmembrane proteins that can either be
      proteolytically cleaved to produce soluble forms of KL or can function as cell
      associated molecules. The c-kit receptor kinase and KL are encoded at the white
      spotting (W) and steel (Sl) loci of the mouse, respectively. Mutations at both
      the W and the Sl locus cause deficiencies in gametogenesis, melanogenesis and
      hematopoiesis. The c-kit receptor is expressed in the cellular targets of W and
      Sl mutations, while KL is expressed in their microenvironment. In melanogenesis,
      c-kit is expressed in melanoblasts from the time they leave the neural crest and
      expression continues during embryonic development and in the melanocytes of
      postnatal animals. In gametogenesis c-kit is expressed in primordial germ cells,
      in spermatogonia, and in primordial and growing oocytes, implying a role at three
      distinct stages of gametogenesis. Many mutant alleles are known at W and Sl loci
      and their phenotypes vary in the degree of severity in the different cellular
      targets of the mutations. While many W and Sl alleles severely affect primordial
      germ cells (PGC), several mild Sl alleles have weak effects on PGCs and exhibit
      differential male or female sterility. Steel Panda (Sl(pan)) is a KL expression
      mutation in which KL RNA transcript levels are reduced in most tissues analyzed.
      In female Sl(pan)/Sl(pan) mice, ovarian follicle development is arrested at the
      one layered cuboidal stage as a result of reduced KL expression in follicle
      cells, indicating a role for c-kit in oocyte growth. Wsh is a c-kit expression
      mutation, which affects mast cells and melanogenesis. While the mast cell defect
      results from lack of c-kit expression, the pigmentation deficiency appears to
      stem from ectopic c-kit receptor expression in the somitic dermatome at the time
      of migration of melanoblasts from the neural crest to the periphery. It is
      proposed that the ectopic c-kit expression in Wsh mice affects early
      melanogenesis in a dominant fashion. The "sash" or white belt of Wsh/+ animals
      and some other mutant mice is explained by the varying density of melanoblasts
      along the body axis of wild-type embryos.

PMID- 7519480
TI  - Molecular basis of reduced or absent expression of decay-accelerating factor in
      Cromer blood group phenotypes.
AB  - The human erythrocyte blood group system Cromer consists of high-incidence and
      low-incidence antigens that reside on decay-accelerating factor (DAF; CD55), a
      glycosyl-phosphatidylinositol-anchored membrane protein that regulates complement
      activation on cell surfaces. In the Cromer phenotypes Dr(a-) and Inab there is
      reduced or absent expression of DAF, respectively. This study investigated the
      molecular basis of the reduced DAF expression by polymerase chain reaction
      amplification of genomic DNA and RNA/cDNA obtained from Epstein-Barr virus
      transformed lymphoblastoid cell lines. Sequence analysis of the Inab propositus
      showed a single nucleotide substitution in exon 2 of the DAF gene and at the
      corresponding position in the cDNA, G314-->A resulting in Trp53-->Stop. This
      truncation near the amino terminus explains the complete absence of surface DAF
      in the Inab phenotype. A similar analysis was performed for two Dr(a-)
      individuals, including KZ, who was previously reported to be Inab phenotype but
      is now shown by immunochemical and serologic methods to be Dr(a-) phenotype. A
      single nucleotide change was found in exon 5 of the DAF gene, C649-->T resulting
      in Ser165-->Leu, which we had previously shown to lead to loss of the Dra
      epitope. However, two species of cDNA were found, one encoding full-length DAF
      with the single amino acid change and the more abundant species having a 44
      nucleotide deletion. The 44 nucleotide deletion includes the single polymorphic
      site, which creates a cryptic branch point in the Dr(a-) allele that leads to use
      of a downstream cryptic acceptor splice site. This shifts the reading frame and
      leads to a premature stop codon that precludes membrane anchoring. Thus, the
      single point mutation in the Dr(a-) phenotype results in a novel use of
      alternative splicing and provides a molecular explanation for both the
      antigenicity and the reduced DAF expression seen in this phenotype.

PMID- 7519483
TI  - Enhancement of the antileukemic activity of 5-aza-2'-deoxycytidine by
      cyclopentenyl cytosine in HL-60 leukemic cells.
AB  - We have investigated the capacity of cyclopentenyl cytosine (CPE-C), a potent
      inhibitor of CTP synthetase, to modulate the antineoplastic activity of 5-aza-2'
      deoxycytidine (DAC) on HL-60 myeloid leukemic cells. The combination of CPE-C and
      DAC produced an additive effect on the growth inhibition of the cells following a
      treatment of 48-96 h. Cytotoxicity experiments measured by the cloning of cells
      in soft agar following 24 and 48 h exposures produced a more than additive effect
      when the drugs were used in combination. Evaluation of the effect of CPE-C and
      DAC on the induction of differentiation of HL-60 cells following a 48 h treatment
      revealed that the combination of the drugs produced a more than additive effect
      than when the drugs were used alone. Measurement of the intracellular pool of
      deoxycytidine triphosphate (dCTP) showed that a 6 h exposure to 0.05 and 0.1
      microM of CPE-C reduced the pool by 60 and 88%, respectively. The decrease in the
      dCTP pool was correlated with a higher incorporation of radioactive DAC into DNA.
      The deamination of CPE-C to cyclopentenyl uridine by cytidine deaminase was
      investigated with the purified enzyme from human placenta. We report here that
      CPE-C is a very poor substrate for cytidine deaminase as compared with cytidine.
      These studies suggest that CPE-C could be used as a biochemical modulator to
      increase the antileukemic action of DAC.

PMID- 7519484
TI  - Clinical and immunological analysis of annular erythema associated with Sjogren
      syndrome.
AB  - Clinical and immunopathological analysis was performed on 24 cases of Sjogren
      syndrome with annular erythema (AESjS). AESjS predominantly appears on the cheek
      of the face where skin temperature is relatively low in comparison with other
      sites. VCAM-1 and ICAM-1 were strongly expressed on endothelial cells of AESjS,
      while epidermal expression of ICAM-1 was focal and weak. VCAM-1 mRNA expression
      was also much more intense compared to systemic lupus erythematosus. The
      lymphocyte response to staphylococcal enterotoxin B was higher in AESjS than that
      of controls, and cells positive for T cell receptor V beta 6,9,12 were expanded
      after the culture. Superantigen-driven endothelial-cell-dependent T cell
      infiltration to the skin plays a crucial role in AESjS.

PMID- 7519485
TI  - Autoimmune response against the bullous pemphigoid 180 autoantigen.
AB  - An immunodominant and potentially pathogenic epitope associated with bullous
      pemphigoid (BP) and herpes gestationis (HG) has recently been mapped by our
      laboratory to a noncollagenous stretch of the extracellular domain of the human
      BP180 antigen. This antigenic site, designated the MCW-1 epitope, has been shown
      to be recognized by the majority of BP and HG sera. Interestingly, the MCW-1
      epitope is absent from the murine BP180 molecule, and therefore, human
      autoantibodies directed against this site could not be tested for pathogenicity
      using the conventional passive transfer mouse model. Alternatively, rabbit
      antibodies were prepared against recombinant forms of the human MCW-1 epitope and
      the murine NC16A domain and were tested for pathogenicity by passive transfer
      experiments. Neonatal mice injected with rabbit antimurine BP180 IgG developed a
      subepidermal blistering disease that closely mimicked BP and HG at the clinical,
      histological and immunological levels. Rabbit IgG specific for the human MCW-1
      epitope was not pathogenic. These results suggest that the autoantibodies against
      the MCW-1 epitope of the human BP180 antigen found in BP and HG sera may be
      relevant in the pathogenesis of blister formation in these patients.

PMID- 7519486
TI  - Production of monoclonal antibodies against the N-terminal noncollagenous domain
      of type VII collagen encoded by epidermolysis bullosa acquisita antigen cDNA.
AB  - Eleven monoclonal antibodies were produced against the human N-terminal
      noncollagenous domain of type VII collagen. All antibodies were specifically
      bound to the epidermal basement membrane zone and did not cross-react with other
      dermal collagens. A binding of these antibodies was investigated with various
      species and revealed that the reactivities of each monoclonal antibody against
      rat, mouse, human and guinea pig skin differ from each other. These data may
      suggest that type VII collagen is antigenic to immunized small animals, i.e. the
      rat and mouse, and that there are multiple antigenic determinants on type VII
      collagen.

PMID- 7519488
TI  - Cross-reactive idiotypes in the sera of patients with bullous pemphigoid express
      anti-basement-membrane-zone activity.
AB  - We have previously generated a monoclonal anti-idiotypic antibody (antiId 3-17)
      specific for a cross-reactive idiotype (CRI) present in sera and bound at the
      basement membrane zone (BMZ) in some patients with bullous pemphigoid (BP). The
      purpose of the present study was to determine if CRI isolated from sera of
      patients with BP expressed anti-BMZ activity. CRI, isolated by affinity
      chromatography from 5 nonrelated patients with BP, bound to the epidermal side of
      normal human split skin as detected by indirect immunofluorescence. In patients
      with BP, the presence of the CRI on circulating IgG is associated with anti-BMZ
      activity.

PMID- 7519490
TI  - Organ transplantation at the Rijeka Clinical Medical Center--from kidney to
      pancreas.
AB  - From January 1971 to January 1994 the authors performed 560 kidney, and two
      simultaneous pancreas and kidney, transplantations at the Rijeka Clinical Medical
      Center. Three hundred and nine kidneys (55%) were from a related living donor
      (two from unrelated living donors), while 253 (45%) kidney and two pancreas
      grafts were from cadaveric donors. Analyzing the mean patients' age at the time
      of transplantation the authors noticed its steady increase over five-year
      periods, a decrease of chronic glomerulonephritis from 76% to 60%, and a gradual
      increase in diabetic nephropathy from 0 to 6%. Cumulative 1- and 5-year patient
      survival rates after living donor transplants including conventional
      immunosuppression were 95 and 83%, respectively; with Cs the survival rates were
      94% and 90% (N. S.). For living donor kidney grafts the 1- and 5-year survival
      rates with conventional immunosuppression were 76% and 50%, respectively. With Cs
      the survival rates were considerably higher: 88% after 1 year and 71% after 5
      years (p < 0.01). Cumulative survival rates of patients with cadaveric
      transplants receiving conventional immunosuppression were 82% and 71%,
      respectively; with Cs they were 87% and 78% (N.S.). The survival rate of
      cadaveric transplants was 51% after one year and 38% after five years in the
      first period, but it improved significantly after introduction of Cs. increasing
      to 81% and 52%, respectively (p < 0.001). Renal transplantation in diabetics does
      not preclude the recurrence of diabetic nephropathy in the graft; successful
      pancreas and kidney transplantation does, however, and thus offers the patient a
      better quality of life.

PMID- 7519487
TI  - Antigenic specificity of antibodies from patients with linear basement membrane
      deposition of IgA.
AB  - We reviewed the immunoreactivity of sera binding to the epidermal side of
      basement membrane split skin from 13 adults and 8 children with IgA alone, 9
      adults with IgA and IgG and 7 adults with IgA and ocular pemphigoid. Immunoblots
      were done against previously described 45-, 97-, 180- and 230-kD antigens, and
      reactivity was confirmed by elution of antibody from nitrocellulose and binding
      to the basement membrane. Ten of 13 adults and 7 of 8 children reacted with the
      97-kD antigen. Sera with both IgA and IgG reacted in varying patterns and on
      occasion with more than 1 antigen. All 7 patients with ocular cicatricial
      pemphigoid reacted uniquely with a 45-kD antigen.

PMID- 7519489
TI  - Molecular effects of T lymphocytes on the regulation of keratin gene expression.
AB  - The interactions between lymphocytes and the epidermis are very important in
      autoimmune skin diseases. Mutual interaction between keratinocytes and T cells is
      effected both by soluble peptides and by direct cell-to-cell contact. We
      investigated the possibility that direct cell-to-cell contact with T cells may
      also play a role in the regulation of keratin gene expression. We have
      transfected human epidermal keratinocytes with the constructs containing
      promoters of keratin genes and then cocultured them with the HUT78 strain of
      human T cells. We found that T cells induce transcription of K5, K6, K14 and K16
      genes, as well as the RSV viral promoter, but not K17, K10 or the SV40 viral
      promoter controls.

PMID- 7519491
TI  - The importance of the clinico-pathological presentations in the evaluation of the
      survival of patients with IgA nephropathy.
AB  - The authors analyzed renal biopsy specimens, clinical data (erythruria/hematuria,
      severity of proteinuria, occurrence of hypertension and renal failure) and
      survival (using the original method by Cutler and Ederer) in 60 patients with IgA
      nephropathy, 34 were male and 26 female aged between 15 and 56 years (32.8 +/-
      9.1). The authors divided all cases in 5 classes taking into consideration
      glomerular changes: class 1 disease-minimal lesions, class 2-minor changes,
      classes 3-focal and segmental lesions, class 4-diffuse proliferation and class 5
      disease-diffuse sclerotic changes. The authors found that: class 1 was younger
      than the others; macroscopic hematuria was more frequent in classes 1 and 2;
      proteinuria was significantly higher in classes and 3; and hypertension was
      absent in class 1 correlating with the severity of glomerular changes.
      Development of chronic renal failure and occurrence of kidney death also
      correlated directly with the severity of histologic glomerular classes.

PMID- 7519492
TI  - Lung correction and mid plane irradiation dose factors in anatomic phantoms of
      proportional sizes.
AB  - In vivo dosimetry in combined anterior-posterior, posterior-anterior, total body
      irradiation (AP-PA TBI) with Co-60 units makes it possible to determine the
      absorbed dose (D) in the patient's mid plane by means of an entrance dose reading
      (R) multiplied by a Mid Plane Dose Factor (MDF) and a Lung Correction Factor
      (CF). A theoretical model of an anatomic phantom, based on a number of
      cylindrical ellipsoide which could be set in any order following a real
      therapeutical position, was established. The dimensions of the constituent parts
      were variable and subject to change. In this work, calculations in the reference
      phantom with volume VO were compared with measurements in two experimental
      anatomic phantoms of the same volume and shape; 1. a water phantom from the
      former investigations and 2. a polystyrene phantom based on real patients' CTs
      with the lungs' inhomogeneities. A generalisation to proportional phantom sizes
      with volume V was set up. It was found that in this approach the ratio V/Vo had a
      significant role in the determination of MDF and CF, when real scattering
      conditions, e.g. lack of scatter due to the finite phantom width, were included.

PMID- 7519493
TI  - Treatment of adult respiratory distress syndrome--our way.
AB  - From July 1991 to September 1992 the authors treated twenty-eight patients with
      proven adult respiratory distress syndrome (ARDS). In this paper five patients
      with ARDS accompanying septicaemia are presented. In this group of patients,
      elevated pulmonary artery pressure or pulmonary hypertension (PAH) could not have
      been caused by LV failure, as it was possible in remaining twenty-three patients
      with ARDS after open heart surgery, so the effect of prostaglandin E1 (PGE1) on
      pulmonary hypertension could be followed accurately. Moreover, ARDS after
      septicaemia carries the worst prognosis. All patients were admitted from other
      hospitals, they were intubated and mechanically ventilated. ARDS was diagnosed 4
      to 7 days after the primary injury.

PMID- 7519494
TI  - Autopsical observations on the blood vessels in the human lower limb.
AB  - The heterolateral femoral triangles (Scarpa's triangles, trigona femoralis) have
      been examined in 48 dead adult subjects of Trieste to detect relevant
      macroanatomical variations, performing the autopsical method. Interesting
      differences have been found in the topography of blood vessels, above all the
      arteries, from that described as normal, or better, more frequent, in the
      literature. The three most relevant anatomical variations for both arteries and
      veins are described in detail; summarizing tables and related graphics are
      presented for the globality of the examined cases. The percentage ratio of the
      observed topographic variations appears to be remarkably different when compared
      to their European frequency and this may be due to the exiguous number of te
      cases (48 subjects, that is, 96 femoral triangles) examined by us; however, the
      three most relevant findings have not been reported in the literature yet.
      Therefore, it is also reasonable to assume that the variations described in this
      study, either for their peculiarity or their relevant frequence, may be explained
      by particular functional hemodynamic needs in the examined population of Trieste,
      as well as by vascular developmental reasons.

PMID- 7519495
TI  - Motor unit hyperactivity states (a correlative clinico-electromyographical
      study).
AB  - The systematic overview of spontaneous motor unit or muscle fiber activity is
      presented. In Part 1 the precise clinical description of fasciculations, myokymia
      and cramps/spasms was made using a dynamic holistic approach. The differences are
      often a matter of excitation quantity. Correlations with electrophysiological
      findings were elaborated on the grounds of literature data and personal
      experience. Electrophysiological correlations with clinically visible
      fasciculations resulted in the finding that the same clinical phenomenon may have
      many entirely different electrophysiological correlates. The special forms of
      repetitive discharges were described additionally: positive giant potentials of
      quadriceps muscles appearing in healthy muscular individuals and grouped
      potential discharges of very chronic nerve ending involvement. The
      electrophysiological features and genesis of many motor unit hyperexcitability
      signs were discussed, while topic differentiation possibilities and symptomatic
      treatment were recommended for some. The spontaneous activity in different
      nosological entities was presented in Part 2. Again the literature data on
      diseases with conspicuous fasciculations, myokymia and cramps with additional
      personal experiences (pesticide intoxication, Isaacs syndrome, hereditary
      autosomal cramp disease, chronic syndrome due to parathyroid insufficiency,
      chronic tetanus and others) were presented. A description was also given of
      personal observations in strictly localized forms: single nerve or root lesions
      and in M. Romberg patient. Symptomatic and causal treatment was suggested for
      some of them. Clinically similar signs may have entirely different causes
      responding specifically to carbamazepine, D3, PAM, or surgical decompression. The
      electromyographic finding may remain clinically silent even in myotonia.

PMID- 7519497
TI  - A history of development of otorhinolaryngology in Croatia.
AB  - The author gives a brief survey of the development of otorhinolaryngology as an
      independent surgical specialization. The clinics on Salata and Vinogradska Street
      have had an important role in the development of the profession and research
      within the field. They have given training to new specialists and reached the
      present level in the development of the profession. They have given their
      scientific contribution to international otorhinolaryngology, paving the way for
      future development of the field in Croatia.

PMID- 7519496
TI  - Epidemiological characteristics of HBV and HDV chronic liver diseases.
AB  - The authors describe the results of prospective examination of the incidence and
      importance of hepatitis B virus and hepatitis D virus in the aetiology of chronic
      liver disease at Slavonski Brod Hospital. HBV incidence is significant in the
      aetiology of chronic liver disease, since it has been found in 100/144 (69.4%) of
      the examinees. Most of the patients were male (75.0%), their mean age was 32.8,
      and their age ranged between 15 and 60. A high percentage (37.0%) was found in
      the category of HBV infection high-risk patients. Most of them were intravenous
      drug addicts, their mean age was 24.9, and they were mostly male (96.9%). In most
      patients HBV infection caused a milder histological and clinical form of chronic
      liver disease, i.e., chronic persistent hepatitis. The disease was recorded in
      62.9% of the patients outside of the high-risk category, and it was found in
      52.6% of the high-risk patients. The incidence of the hepatitis D virus in the
      aetiology of chronic liver disease was found in 19/100 (19.0%) of the HBV
      positive patients. 18/19 of the HDV infection patients belonged to the high-risk
      category, 16 of them being drug addicts. Hepatitis D virus infection led to
      serious clinical and histological forms of chronic liver disease in most cases:
      chronic active hepatitis and cirrhosis of the liver in 89.5% of the cases, and
      chronic persistent hepatitis in only 19.5% of the cases.

PMID- 7519498
TI  - Osteocalcin reference range in a Croatian population sample.
AB  - Osteocalcin concentrations were measured in 40 healthy males and 60 healthy
      females aged 21-90 years by a commercial RIA kit. No significant difference
      between sexes was found for osteocalcin, and a negative and exponential
      regression with age existed only for females. In comparison to reference values
      of other investigators, higher osteocalcin concentrations were observed and
      considered consequential to sample selection and wide age range. Validity of the
      established reference range (1-18 ng/mL) was confirmed by measuring osteocalcin
      in patients with different bone metabolism disorders.

PMID- 7519499
TI  - Thyroid peroxidase prevails over thyroid microsomal and thyroglobulin antibodies
      in thyroidal and nonthyroidal illnesses.
AB  - Autoimmune thyroid disease is usually related to the presence of autoantibodies
      (TPO, TMA, TGA, TSH-R) in patients' sera. In this study the presence of
      autoantibodies in the sera of patients with thyroid disease, patients with end
      stage renal disease and in several groups of euthyroid subjects have been
      evaluated (N = 217). The percentages of positive values detected in six groups
      ranged: 0-47%, 2-94% and 3-100% for TGA, TMA, and TPO, respectively.
      Autoantibodies were mostly present in the sera of patients with Hashimoto
      thyroiditis (TPO 100%, TMA 94%, TGA 47%), and sporadically in the control
      subjects (TPO 4%, TMA 2%, TGA 0%). Authors's results confirm the prevalence of
      TPO over TGA and TMA in the sera of all investigated groups. The authors did not
      find changes in ATA levels during methimazole therapy of their patients with
      Graves' disease. Some of serum autoantibodies were constantly present or absent
      in spite of remission.

PMID- 7519500
TI  - Flow-cytometric lymphocyte phenotyping using automated SimulSET Software gating
      procedure.
AB  - The peripheral blood lymphocyte phenotypes of 20 healthy young normal subjects
      between the ages 21 and 29 were determined by dual fluorescence analysis with
      fluorochrome--labeled monoclonal antibodies (mAbs). Samples were prepared by a
      whole blood lysis technique and analysed on a FACScan flow cytometer using
      SimulSET Software. Values for lymphocyte subpopulations (percentage and absolute
      count) are presented. Some values are different in relation to sex. The most
      important steps in SimulSET software gating procedure of lymphocytes are also
      described.

PMID- 7519501
TI  - Nasopharyngeal cancer and blood selenium level.
AB  - A case-control study of nasopharyngeal carcinoma was performed in Zagreb from
      1989 until 1993. Blood selenium concentrations were determined in 34 patients
      with nasopharyngeal cancer and 47 normal subjects by means of the atomic
      absorption spectrophotometric method. The sera of nasopharyngeal cancer patients
      showed no significant differences in selenium values from the sera of normal
      individuals, but there were significant differences between patients with
      enlarged cancer (T4 stage) and normal individuals. The results suggest that lower
      blood selenium levels in this group of nasopharyngeal cancer patients may be a
      consequence of their disease, rather than the cause of the cancer.

PMID- 7519502
TI  - The HBe antigen-antibody system and its relationship to epidemiological,
      histological and biochemical findings in patients with HBV+ HDV chronic liver
      diseases.
AB  - The authors describe the results of prospective research on the HBeAg-anti-HBe
      system in 81 HBV patients and on HBV+ HDV chronic liver disease in 19 patients
      who were treated at Slavonski Brod Medical Centre. They analyze the correlation
      between various epidemiological groups of patients, liver disease activity and
      the condition of the HBeAg-anti-HBe system in chronic HBV and HDV infection. A
      clear correlation was established between the presence of HBe antigen and the
      patients' youth, the pathological alanin aminotransferase values and
      pathohistological liver findings. In as many as 64.4% of the HBeAg-positive
      patients the active chronic liver disease process was verified. However, this
      pathological activity was also verified in 36.4% of the HBeAg-negative patients
      with chronic HBV infection. Moreover, anti-HBe was found more often in the serum
      of the hepatitis D infected patients (68.4%). Serious forms of chronic liver
      disease were found in all of the HDV-positive patients with the anti-HBe finding
      in serum. However, chronic active hepatitis or cirrhosis of the liver was found
      in only 23.5% of the HBeAg-positive patients suffering from HDV infection. We
      should point out that the HBeAg-anti-HBe system does not have an absolute value
      in the estimation of histological liver changes and in the prognosis of chronic
      liver disease for individual patients.

PMID- 7519503
TI  - Trimestral changes of seizure frequency in pregnant epileptic women.
AB  - The aim of this study was to assess the influence of pregnancy on trimestral
      frequency of epileptic seizures. The seizure frequency was studied
      retrospectively in 50 pregnant epileptic women compared to one year before the
      onset of pregnancy, for each trimester of pregnancy separately, and for the whole
      duration of pregnancy. In the first trimester 18% of the pregnant epileptic women
      had an increased seizure frequency. There was no change in seizure frequency in
      56% of pregnancies. In 26% of the pregnant women the number of seizures was
      decreased. In the second trimester, pregnancy did not influence seizure frequency
      in 60% of the pregnancies; 16% of the women had increased frequency of seizures
      and 24% had decreased frequency. In the third trimester, 20% of the pregnant
      epileptic women had higher seizure frequency. In 56% of the women no change in
      seizure frequency was recorded during pregnancy. For the entire period of
      pregnancy, 22% of the pregnant epileptic women had an increased seizure
      frequency, 54% had no change, and 24% had lower frequency as compared to one year
      before conception. No difference of seizure frequency was noted between
      trimesters and the whole course of pregnancy.

PMID- 7519504
TI  - An analysis of total expenditures on hospitalized patients with diarrhoeal
      syndrome.
AB  - Between the months of June, July, August and September 1992, 175 patients with
      acute diarrhoeal syndrome were treated at the University Department for
      Infectious diseases in Rijeka. Among them were 28 refugees and 7 members of the
      Croatian Army forces. Etiologic agents were isolated in 69 patients, among which
      61 was Salmonella. The total cost of treatment was 9.737,203 Croatian Dinars or
      51,529 German Marks, obtained on monthly reevaluation of expenditures. A total of
      33.3% was spent on accommodation and feeding which was 6% decrease at the on of
      treatment. On further treatment cost was 33.7%, microbiologic examinations 13.1%,
      while biochemical examinations was 12.1%. Of the total cost, the X-ray,
      ultrasound and specialist examinations carried the lowest price of the cost of
      treatment. Reduction of the cost could be achieved by reducing the duration of
      hospitalization, which averaged about 8 days per each patient. The routine
      microbiologic and serologic analysis should be repeated rationally.

PMID- 7519505
TI  - Hepatitis markers in Malaysians with hepatocellular carcinoma.
AB  - Sera from 80 Malaysians with confirmed hepatocellular carcinoma were tested for
      five markers of the hepatitis B virus, anti-HCV and anti-HDV by enzyme
      immunoassay, and alpha fetoprotein (AFP) was measured by radioimmunoassay. Of the
      patients, 98.8% had evidence of HBV infection and 75% were positive for HBsAg-
      which latter correlated with AFP raised above cut-off values of 500 ng/ml (P =
      0.0001) and 200 ng/ml (P = 0.005). Males correlated significantly with the
      presence of HBsAg (P = 0.002). Thirty-one per cent of HBsAg positive patients
      were also positive for HBeAg and 74% for anti-HBe. Twenty per cent of the cases
      were concurrently positive for both HBsAg and anti-HBs. Six of 70 (8.6%) patients
      were positive for anti-HCV, of whom four were also positive for HBsAg. None of 67
      patients tested for anti-HDV were positive. The results strongly indicate an
      important aetiological role for hepatitis B virus in causation of hepatocellular
      carcinoma among Malaysians.

PMID- 7519507
TI  - The expression of FMS, KIT and FLT3 in hematopoietic malignancies.
AB  - Three receptor molecules, belonging to the class III of receptor tyrosine
      kinases, namely the receptors for colony-stimulating factor 1, CSF1R (product of
      the FMS proto-oncogene) and Steel factor, SLFR (product of the KIT proto
      oncogene), as well as the recently identified FLT3/FLK2 gene product, appear to
      play distinct roles in normal hematopoietic differentiation. Their potential role
      in leukemic hematopoiesis has been approached by expression studies in
      hematopoietic malignancies, especially in acute leukemias of the myeloid and
      lymphoid lineages. We present here a review of available data, and discuss the
      possible significance and potential applications of these results.

PMID- 7519506
TI  - Histological characteristics of breast carcinoma in blacks and whites.
AB  - Tumor characteristics of 963 newly diagnosed invasive breast cancer cases from
      the population-based Black/White Cancer Survival Study were evaluated.
      Representative slides of the tumors were requested from all participating
      hospitals of three metropolitan areas and reviewed by one expert pathologist,
      blinded in regard to the age and race of patients. Nine tumor characteristics
      were evaluated for black and white patients. After adjusting for age, stage, and
      metropolitan area, blacks were significantly more likely to have high grade
      nuclear atypia [odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.27
      3.04]; high mitotic activity (OR = 2.05, 95% CI = 1.34-3.14), grade 3 tumors (OR
      = 1.58, 95% CI = 1.02-2.45), and more necrosis (OR = 1.51, 95% CI = 1.16-1.98);
      and less likely to have well defined tubular formation (OR = 0.57, 95% CI = 0.42
      0.77), marked fibrosis (OR = 0.65, 95% CI = 0.45-0.94), and positive estrogen
      receptor status (OR = 0.78, 95% CI = 0.58-1.05). These black/white differences
      remained after controlling for socioeconomic status (SES), body mass index, use
      of alcohol and tobacco, reproductive experience, and health care access and
      utilization. No significant racial differences were found for blood vessel
      invasion and lymphatic invasion. Although white women of high SES had more
      favorable tumors than those of low SES, the same pattern was not observed for
      blacks. High SES black women had statistically nonsignificant elevated ORs of a
      high mitotic index and tumor grade. These racial differences in tumor biology may
      have etiological and clinical implications.

PMID- 7519508
TI  - Endogenous production and peripheral blood levels of granulocyte-macrophage (GM-)
      and granulocyte (G-) colony-stimulating factors.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony
      stimulating factor (G-CSF) are two important granulopoietic growth factors. This
      review will focus on the endogenous production of human GM-CSF and human G-CSF
      and its possible reflection in circulating levels in peripheral blood. When
      adequately stimulated a variety of cell-types such as monocytes/macrophages. T
      lymphocytes, endothelial cells and fibroblasts can produce CSFs in vitro. G-CSF
      can increase to detectable levels in peripheral blood when there is a demand for
      granulocyte production such as acute neutropenic in conjunction with
      hematological disorders, chronic neutropenic conditions and acute infectious
      diseases in patients with or without underlying hematological disorders. G-CSF in
      peripheral blood is detected more often and in higher concentrations than GM-CSF.
      An independent regulation of GM-CSF and G-CSF secretion, quantitative differences
      in production and/or differences in elimination or distribution might be of
      importance.

PMID- 7519509
TI  - Expression of adhesion molecules CD11/CD18 (Leu-CAMs, beta 2-integrins), CD54
      (ICAM-1) and CD58 (LFA-3) in B-chronic lymphocytic leukemia.
AB  - Cell adhesion molecules (CAMs) are cell surface proteins with unique
      specificities that allow intercellular adhesion. The importance of CAMs for
      normal lymphocyte growth and differentiation is underscored by the association
      between neoplastic disease states and abnormal CAM expression. In the present
      study we analysed the cell surface expression of several CAMs on peripheral blood
      lymphocytes from patients with progressive chronic lymphocytic leukemia of B-cell
      type (B-CLL) (n = 21) and stable monoclonal B-lymphocytosis of undetermined
      significance (B-MLUS) (n = 20). The CAM expression was analysed on the B-cell
      clone and on normal T- and NK-cell populations separately using monoclonal
      antibodies (MAbs). A phorbol ester-induced lymphocyte aggregation assay and
      blocking MAbs were also used. The B-cell clone in B-CLL expressed ICAM-1 (CD54)
      more frequently and at a higher density than in B-MLUS. The brightest CD54
      expression was noted in patients with prominent lymphadenopathy and/or
      splenomegaly. The beta 2 integrin CD11a (Leu-CAMa, LFA-1) was detected on some B
      cell clones and seemed to relate to tissue localization of the disease. T and NK
      cells showed a low expression of CD11a in B-CLL patients, while in B-MLUS a high
      proportion of non-clonal cells coexpressed CD11a with a high staining intensity.
      The relative numbers of both CD18+ as well as CD2+ cells showed a positive
      correlation with phorbol ester induced cell aggregation in B-MLUS patients (p <
      0.05). The aggregation was blocked by adding MAbs against CD18 in most cases but
      to a greater extent in B-CLL. These results extend and corroborate our earlier
      findings on surface phenotypic characteristics of clonal and non-clonal
      lymphocytes in different clinical subtypes of B-CLL. CAM expression on the
      monoclonal lymphocytes may play a role in their interaction with regulatory
      immune cells and their tissue localization.

PMID- 7519511
TI  - Sarcoidosis following chemotherapy for Hodgkin's disease.
AB  - A case report describing persistent paratracheal lymphadenopathy after
      doxorubicin, bleomycin, vinblastin, and dacarbazine (ABVD) chemotherapy for a
      patient with Hodgkin's disease (HD) is presented. Mediastinoscopy and biopsy of
      the paratracheal lymph nodes showed non-caseating granulomas characteristic of
      sarcoidosis. The authors discuss the relationship between sarcoidosis and HD and
      hypothesize that the development or progression of sarcoidosis in a patient with
      HD is a potential consequence of chemotherapy. Two possible mechanisms are
      proposed. The first includes the immunosuppressive effect of chemotherapy and the
      second implicates the influence of a specific chemotherapy agent, bleomycin,
      which is known to have relatively higher lymph node, skin and lung tissue
      concentrations than other agents included in the ABVD regimen, and a predilection
      for those tissues that are prone for the development of sarcoidosis. With the
      incidence of sarcoidosis exceeding that of HD for the general population, the
      authors emphasize the importance of considering the presence of sarcoidosis in
      the differential diagnosis of patients who do not respond radiographically to HD
      chemotherapy.

PMID- 7519510
TI  - Hairy cell leukemia: a clinical review based on 725 cases of the Italian
      Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia.
AB  - The Italian Registry for hairy cell leukemia (HCL) has recorded 725 patients with
      HCL diagnosed over 25 years. We analysed this large series of patients with the
      aim of providing an evaluation of changes in clinical presentation, impact of
      initial therapy and modifications in prognostic factors over the period of two
      decades. Over time, a progressive down-staging of the disease at the onset, along
      with a reduction of patients with severe anemia and marked splenomegaly, has been
      observed. A second malignancy was found in 3.7% of patients, mostly detected
      several years after the onset of HCL. A striking improvement of survival rates
      has been observed, from 58.9% survival at five years for patients diagnosed
      before 1985 to 87.5% at five years for patients diagnosed after 1985 (p <
      0.0001). Before 1985 hemoglobin alone provided prognostic information, whereas
      after 1985, clinical stage and the number of leukocytes correlated better with
      patient outcome. Survivals at 5 and 10 years were 34.4% and 29.6% respectively
      for untreated patients, 58.8% and 44.1% for patients receiving chemotherapy,
      steroids or other drugs, 64.1% and 56.1% for splenectomized patients and 88.9%
      (at 5 years) for alpha interferon (IFN)-treated patients (p < 0.0001). Our
      findings suggest that IFN has improved the prognosis of HCL, and that it must be
      considered a good initial treatment for patients with HCL.

PMID- 7519512
TI  - Role of phosphorylated MAPlB in neuritogenesis.
AB  - The distribution of microtubule-associated protein lB (MAPlB) phosphorylated by
      either proline-directed protein kinase (PDPK) or casein kinase II (CK II) in
      neuroblastoma cells and hippocampal neurons has been studied by
      immunofluorescence using specific antibodies to distinct phosphorylation
      sensitive epitopes. A proximo-distal gradient of increasing PDPK-catalyzed
      phosphorylation of MAPlB is superimposed on a proximo distal gradient of
      decreasing CK II-catalyzed MAPlB phosphorylation within growing axon-like
      neurites. Additionally, CK II-phosphorylated MAPlB is present in cell bodies and
      dendrites where no PDPK-phosphorylated MAPlB is observed. These results suggest
      distinct roles for both types of modifications of MAPlB in developing neurons.

PMID- 7519514
TI  - Surveillance of HTLV infection in England and Wales: 1986-1992.
AB  - The epidemiology of infection with human T cell leukaemia/lymphoma virus (HTLV)
      types I and II in England and Wales between 1986 and 1992 has been studied. Two
      sources of data have been reviewed: reports of cases of infection received by the
      PHLS Communicable Disease Surveillance Centre, and information about people
      infected with HTLV-I and II provided on laboratory request forms sent to the
      Virus Reference Division of the PHLS Central Public Health Laboratory. Most
      patients were of Caribbean origin. The age and sex distribution of people with
      disease associated with HTLV-I and II in England and Wales resembles that
      previously recorded in the Caribbean. The data suggest that the prevalence of
      disease associated with HTLV infection is low in England and Wales, but case
      ascertainment may be incomplete.

PMID- 7519513
TI  - Projections from ventrolateral hypothalamic neurons containing progestin receptor
      and substance P-immunoreactivity to specific forebrain and midbrain areas in
      female guinea pigs.
AB  - Many neurons within the ventrolateral hypothalamus in guinea pigs contain
      estrogen-induced progestin receptors as well as substance P. Retrograde tracing
      combined with immunocytochemistry was used to determine the specific projections
      of this subset of steroid-sensitive cells. Unilateral Fluoro-Gold injections into
      the dorsal midbrain, including the central gray, labeled a large proportion of
      the ventrolateral hypothalamic neurons immunoreactive for both progestin
      receptors and substance P (approximately 30%); substantially fewer of these
      neurons were labeled by unilateral Fluoro-Gold injections into the preoptic area
      (approximately 6%), medial amygdala (approximately 10%), or the bed nucleus of
      the stria terminalis (approximately 11%). The projections of progestin receptor
      immunoreactive neurons in the ventrolateral hypothalamus were similar to those of
      progestin receptor/substance P double-labeled neurons, while a slightly lower
      percentage of the ventrolateral hypothalamic, substance P-immunoreactive neurons
      tended to project to each of these areas. These pathways may prove to be
      components of the neural circuitry underlying a variety of functions influenced
      by gonadal steroid hormones and substance P, such as female sexual behavior, salt
      intake, nociception and aggression.

PMID- 7519515
TI  - Measles in secondary school children: implications for vaccination policy.
AB  - The reported incidence of measles in children of secondary school age rose in
      1992, after a progressive decline between 1988 and 1991. This rise was maintained
      in 1993. Several school and community based outbreaks of measles have occurred in
      the United Kingdom. This paper reports the investigation of an outbreak of
      measles based in a secondary school, which took place in 1992. Thirty clinical
      cases were detected among the school's 840 pupils and 10 sporadic cases occurred
      outside the school. Twenty-one of the school cases provided samples of serum, in
      19 of which measles IgM was detected. The overall attack rate was 3.6%, with no
      significant differences attributable to age and sex. Vaccine efficacy was about
      90%. This outbreak is one of the first to be described in the United Kingdom,
      although other countries (notably the United States) have reported measles in
      teenagers. The small degree of spread in the community may reflect the current
      high uptake of measles, mumps, and rubella vaccine and the catch up campaign that
      took place in 1988. The feasibility and cost effectiveness of various policy
      options to prevent future outbreaks in secondary schools are now being evaluated.

PMID- 7519516
TI  - An outbreak of measles in Trafford.
AB  - In the autumn of 1993 an outbreak of measles occurred in Trafford, Greater
      Manchester, associated with two junior schools. Thirty-four cases were reported.
      Twenty-five of the 32 cases whose ages were known were aged between 7 and 11
      years. The mean age was 8.6 years, and the median and modal age was 10. Two of
      the cases had received measles vaccine. Eighteen of the 19 cases who provided
      samples were confirmed as measles by laboratory tests. The incident showed that
      extensive resources are needed to investigate such outbreaks and implement
      control measures, and identified problems with the local child health computer
      system. The outbreak did, however, provide an opportunity to immunise children
      within the district who had not previously received measles vaccine. It is
      important for unprotected siblings of affected children to be vaccinated to
      prevent the secondary spread of infection, and all cases of measles should be
      notified promptly so that outbreaks can be identified.

PMID- 7519518
TI  - Measles surveillance.

PMID- 7519517
TI  - Invasive group A streptococcal infections in Gloucestershire.

PMID- 7519519
TI  - Limiting but not abandoning treatment in severely mentally impaired patients: a
      troubling issue for ethics consultants and ethics committees.

PMID- 7519520
TI  - Phylogeny of sibling species of Simulium venustum and S. verecundum (Diptera:
      Simuliidae) based on sequences of the mitochondrial 16S rRNA gene.
AB  - The phylogeny of four sibling species of Simulium venustum (CC, CC3, CC4, and
      AC(gB)) and two sibling species of S. verecundum (AA and ACD = S. rostratum) was
      reconstructed using nucleotide sequences of the mitochondrial large subunit rRNA
      gene. Separate phylogenetic analyses were performed by dividing the sequence data
      into: (1) helices of a computer-generated secondary structure of the rDNA; (2)
      loops of the computer-generated structure; (3) helices of a consensus secondary
      structure (deduced by comparing the computer-generated structure of black flies
      with the corresponding structures proposed for the fruit fly (Drosophila yakuba)
      and the mosquito (Aedes albopictus)); (4) loops of the consensus structure; (5)
      both helices and loops of the consensus secondary structure; and (6) the entire
      sequence regardless of secondary structure, including 11 variable sites in
      regions where the prediction of secondary structure was not possible. We found
      that different data sets led to different phylogenetic conclusions. The
      phylogenies based on data sets 4 and 6 were consistent with nonmolecular
      evidence, while the phylogenies based on other data sets were not. Our study
      suggests S. decorum, a morphospecies, might have shared a common ancestor with
      sibling species of S. venustum.

PMID- 7519522
TI  - The use of endoprosthesis in the palliation of esophageal carcinoma.
AB  - Dilatation and palliative intubation of esophageal cancer is probably one of the
      most dangerous operations in esophageal surgery. For a significant portion of
      patients, it provides a valuable improvement in the comfort of swallowing.
      Current techniques of intubation are reviewed, as well as their morbidity and
      mortality.

PMID- 7519521
TI  - Antigen-induced airway responses are inhibited by a potassium channel opener.
AB  - We have investigated the effect of a potassium channel opener, BRL 38227, on
      antigen-induced bronchoconstriction and airway microvascular leakage in
      sensitized guinea pigs by simultaneously measuring pulmonary resistance (Rl) and
      extravasation of Evans blue dye. Guinea pigs were sensitized 3 wk before
      experimentation with ovalbumin (OA) and aluminum hydroxide. The trachea was
      cannulated, and lungs were mechanically ventilated. All animals were pretreated
      30 min before experimentation with atropine (1 mg/kg intravenously) and
      propranolol 1 mg/kg to block muscarinic and beta-adrenergic responses,
      respectively. BRL 38227 (200 micrograms/kg) was administered intravenously 1 min
      before intravenous dye injection (30 mg/kg); OA (3 mg/ml) was inhaled using an
      ultrasonic nebulizer (for 30 s) 1 min after dye injection. BRL 38227
      significantly inhibited OA-induced bronchoconstrictor response (p < 0.01) and
      plasma leakage in trachea (p < 0.05) and main bronchi (p < 0.05). BRL 38227 also
      had an inhibitory effect on exogenous histamine- and leukotriene-induced
      bronchoconstriction and microvascular leakage. However, BRL 38227 did not affect
      OA-induced histamine release from minced lung tissues in sensitized guinea pigs.
      We conclude that the allergic bronchoconstrictor response and airway plasma
      leakage are inhibited by a potassium channel opener, possibly as a result of its
      effect on the airway smooth muscle and the postcapillary venule level.

PMID- 7519525
TI  - The involvement of sympathetic nerves in plasma extravasation induced by
      prostaglandin E2 and substance P.
AB  - The effects of intravenous injection of prostaglandin E2 (PGE2), substance P (SP)
      and a metabolically stable SP analogue, [pGlu5,Me-Phe8,Sar9]-SP (5-11) on plasma
      extravasation of albumin in the rat after blockade of prostaglandin synthesis
      with indomethacin or chemical sympathectomy with guanethidine were studied. Blood
      pressure was decreased by all agonists, but only the hypotensive effects of SP
      were enhanced by pretreatment with indomethacin and guanethidine. The increase in
      plasma extravasation induced by PGE2 in the tongue, skin and lungs was blocked by
      both guanethidine and indomethacin. Pretreatment of the rats with guanethidine or
      indomethacin increased extravasation induced by SP in the tongue-tip, dorsal skin
      and foot, but decreased the enhanced permeability in the pinna, and did not alter
      the actions of the peptide in other tissues. In contrast, both guanethidine and
      indomethacin pretreatment increased vascular permeability responses to [pGlu5,Me
      Phe8,Sar9]-SP (5-11) administration in 9 and 14 of 16 tissues examined,
      respectively. Thus, intact sympathetic nerves and functional cycloxygenase
      activity exert inhibitory constraints on the vascular permeability effects of
      intravenously administered SP or its analogue. On the other hand the integrity of
      the sympathetic nerves and prostaglandin synthesis are required for PGE2-induced
      increases in vascular leak.

PMID- 7519523
TI  - Palliation of esophageal carcinoma. Laser and photodynamic therapy.
AB  - Laser therapy is a well-established, relatively safe, rapid, and highly effective
      method of palliation for the dysphagia that usually accompanies esophageal and
      esophagogastric cancer. It is the treatment of choice in many patients, although
      there remains some disagreement regarding technique and predictors of outcome.
      The major limitation of laser therapy is the need for repeated treatments,
      although the interval between treatments may be lengthened by concomitant
      external beam or endoluminal radiotherapy. When laser therapy is available, use
      of an esophageal stent should be reserved for special circumstances, such as
      esophagopulmonary fistulas or extrinsic compression. In addition, stent placement
      usually is effective when laser photoablation fails or must be performed too
      frequently. It remains to be seen whether or not technical improvements in
      esophageal stents will reduce the frequency of complications associated with
      these devices. Other promising modalities that may be less expensive and more
      readily available, such as the BICAP tumor probe or injection therapy, deserve
      further study. It appears that most of these methods are complementary and
      different modalities may be suited to different types of lesions. The results of
      phase III clinical trials with PDT, now underway, should help to define the role
      of this promising modality in the overall scheme of treatment for esophageal
      cancer. The concept of PDT is attractive, although refinements in photosensitive
      compounds and methods of light delivery may be needed. Current information
      suggests a moderately high complication rate for PDT, although this may decrease
      with technical improvements and increasing experience. Issues surrounding the
      palliation of esophageal cancer are complex. Whereas the tendency is to focus on
      technical aspects of therapy and the relief of dysphagia, broader aspects of a
      patient's quality of life cannot be ignored. Ultimately, the choice of therapy
      may depend as much on a patient's psychosocial circumstances as on the appearance
      of the lesion. For instance, the patient who lives at a great distance from the
      center where laser therapy is performed may be better served by placement of an
      esophageal stent despite the higher complication rate for this procedure. PDT
      would be inappropriate for the patient who wishes to spend the remaining few
      months of life outdoors in the sun. Guiding the patient to the best choice
      requires the skills of a physician as much as the technical ability of an
      endoscopist.

PMID- 7519526
TI  - Nitric oxide synthase increases in hypothalamic magnocellular neurons after salt
      loading in the rat. An immunohistochemical and in situ hybridization study.
AB  - Magnocellular hypothalamic neurons of the paraventricular (PVN) and supraoptic
      (SON) nuclei have been shown to contain a wide variety of messenger molecules in
      addition to vasopressin and oxytocin, including the nitric oxide (NO)
      synthesizing enzyme (NOS). In this paper we have investigated the effects of salt
      loading on the expression of NOS by means of immunohistochemistry and in-situ
      hybridization. The results show an increase in the number of NOS-immunoreactive
      (IR) neurons both in the PVN and the SON after 5 and 14 days of salt loading.
      Several of these neurons were double labelled with vasopressin antiserum. In situ
      hybridization showed a marked increase in the number of neurons expressing NOS
      mRNA and a stronger signal in individual neurons. The present results suggest a
      role for NO in the magnocellular hypothalamic system after salt loading.

PMID- 7519524
TI  - Nicotine-induced protection of cultured cortical neurons against N-methyl-D
      aspartate receptor-mediated glutamate cytotoxicity.
AB  - The effects of nicotine on glutamate-induced cytotoxicity were examined using
      primary cultures of rat cortical neurons. The cell viability was significantly
      reduced when cultures were briefly exposed to glutamate or N-methyl-D-aspartate
      (NMDA) then incubated with normal medium for 1 h. A 1-h exposure of the cultures
      to kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)
      reduced cell viability. Incubating cultures with nicotine for 1-24 h protected
      cortical neurons against glutamate cytotoxicity. Maximum protection against
      glutamate cytotoxicity was induced with a 2-h nicotine incubation. Exposure to
      nicotine for up to 2 h did not affect cell viability by itself although cell
      viability was reduced in a time-dependent manner when the exposure exceeded 4 h.
      Neuroprotection by nicotine was dependent on both the concentration and
      incubation period. Nicotine reduced the NMDA cytotoxicity but did not attenuate
      that of kainate and AMPA. The neuroprotective effects of nicotine against
      glutamate cytotoxicity were antagonized by mecamylamine and hexamethonium but not
      by atropine. These results indicate that nicotinic receptor stimulation induces
      neuroprotection against glutamate cytotoxicity mediated by NMDA receptors.

PMID- 7519527
TI  - Tachykinin-mediated increase in motility acts independently of vasoactive
      intestinal polypeptide release in the canine ileum.
AB  - Tachykinins induce motor activity in the canine ileum, and their mechanism of
      excitation may include inhibition of the release of a nonadrenergic,
      noncholinergic inhibitor, for which vasoactive intestinal polypeptide (VIP) is a
      candidate. Both substance P and neurokinin A produced a dose-dependent increase
      in ileal contractility with no significant change in VIP output. The highly
      selective NK1 agonist [Sar9, Met(O2)11]substance P and the highly selective NK2
      agonist [Nle10]neurokinin A (4-10) also increased motor activity in the absence
      of any change in VIP released. These data suggest that the tachykinins produce
      motor activity in the canine ileum via a mechanism that does not involve changes
      in VIP output but may involve excitation through both NK1 and NK2 receptors.

PMID- 7519529
TI  - The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF
      binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is
      increased in acromegalic patients.
AB  - OBJECTIVE: Several in-vitro studies have suggested that the biological actions of
      IGF-I can be modified by the presence of specific IGF binding proteins. In man,
      the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term
      changes in the IGF-I/IGFBP-3 ratio have been described following GH
      administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal
      adults and are elevated in active acromegaly due to excessive GH secretion.
      However, the individual ratios between serum levels of IGF-I and IGFBP-3 in
      acromegalic and healthy adults have not been described previously. METHODS AND
      MATERIALS: We studied this ratio in 198 healthy adults and in 56 acromegalic
      patients, grouped according to their serum GH levels (group I GH < 2mIU/l II GH 2
      10 mIU/l; III GH > 10 mIU/l). In all subjects a single blood sample was drawn for
      IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and GH measurements by specific RIAs. In
      38 of the patients a 24-hour urinary collection was performed for GH
      determination. RESULTS: In healthy adults serum levels of IGF-I and IGFBP-3
      decreased with increasing age (r = -0.52 and r = -0.34, respectively, P <
      0.0001). In addition, the molar IGF-I/IGFBP-3 ratio declined with increasing age
      (r = -0.44, P = 0.0001). In patients with acromegaly and high serum GH levels
      (group III), circulating IGF-I was increased 7.97 standard deviations (SDS) and
      IGFBP-3 was increased 4.20 SDS (P < 0.0001). Serum levels of IGF-II were normal
      in all three groups (588 +/- 240 micrograms/l) whereas IGFBP-1 and IGFBP-2 levels
      were low and IGFBP-2 levels decreased significantly with increasing serum GH
      levels (P < 0.0001). The molar IGF-I/IGFBP-3 ratio in the acromegalic patients
      was significantly higher than in the controls (P < 0.0001) and correlated
      significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with
      serum GH levels (r = 0.73, P < 0.0001). CONCLUSION: We demonstrated a decreasing
      molar IGF-I/IGFBP-3 ratio with increasing age in healthy adults and an increased
      ratio between serum IGF-I and IGFBP-3 levels in acromegalic patients. As IGF-II
      is normal and IGFBP-1 and IGFBP-2 are inversely correlated to the serum GH levels
      in the acromegalic patients, we speculate that the molar ratio between IGF-I and
      IGFBP-3 reflects free (biologically active) IGF-I and is dependent on GH levels.

PMID- 7519528
TI  - Effect of FK-506 on xenografted human Graves' thyroid tissue is severe combined
      immunodeficient mice.
AB  - OBJECTIVE: We studied the macrolide antibiotic FK-506, an immunosuppressive
      agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in
      human thyroid tissue xenografted into severe combined immunodeficient (SCID)
      mice. It was not felt appropriate to employ this agent directly in patients with
      autoimmune thyroid disease because adequate therapeutic modalities are available
      and the introduction of new, experimental agents could not be justified.
      Moreover, the study of the tissue before and after treatment could not have been
      undertaken directly in patients. DESIGN: Human thyroid xenografts from four
      patients with Graves' disease and two normal persons were xenografted into SCID
      mice. Two weeks after xenografting, human immunoglobulin G (IgG) was detectable
      in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into
      two groups with human IgG levels similar to each other. Mice in the first group
      were treated with FK-506 daily for 6 weeks; mice in the second (similar) group
      were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS:
      Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid
      stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and
      interferon-gamma (IFN-gamma). After 8 weeks treatment, animals were sacrificed;
      thyroid tissue was examined histologically and for thyrocyte HLA-DR expression.
      FK-506 was also added to thyrocytes in in-vitro tissue culture conditions.
      RESULTS: After 4-6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and
      IFN-gamma were suppressed, while the levels remained elevated in the control
      group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue
      of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in
      the control mice, lymphocytic infiltration remained heavy and HLA-DR expression
      remained high. On the other hand, FK-506 added directly to thyrocytes in vitro
      (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS: FK
      506 appears to suppress the activation of intrathyroidal lymphocytes, but not
      thyrocytes. From these observations, it is concluded that this agent, by its
      action on intrathyroidal lymphocytes, is able to ameliorate the immunologically
      mediated histological and serological disturbance in human autoimmune thyroid
      disease, at least under these circumstances.

PMID- 7519530
TI  - Heat shock protein peptides reactive in patients with Behcet's disease are
      uveitogenic in Lewis rats.
AB  - Mycobacterial and homologous human heat shock protein T cell peptide epitopes
      specific for T lymphocytes in Behcet's disease were investigated for their
      pathogenicity in Lewis rats. The potential pathogenicity of eight peptides and
      two controls was assessed by administering the peptides in enriched Freund's
      adjuvant into the footpads of male Lewis rats. Anterior uveitis which is a major
      manifestation of Behcet's disease was induced with two out of the four
      mycobacterial and all four homologous human peptides. The most effective peptides
      inducing iridocyclitis in 64-75% of rats were peptides with amino acids 336-351
      and 136-150, derived from the sequence of the human 60-kD heat shock protein. A
      few of the rats also showed evidence of focal loss of photoreceptors. These
      results suggest that selected peptides within heat shock protein 60 kD which
      function as T cell epitopes in Behcet's disease are capable of inducing uveitis
      in rats. This supports the view that the peptide T cell determinants may be
      involved in the pathogenesis of Behcet's disease.

PMID- 7519531
TI  - Expression of the gene for inducible nitric oxide synthase in experimental
      glomerulonephritis in the rat.
AB  - Nitrite, a stable product of nitric oxide (NO), is synthesized in vitro by
      glomeruli in experimental glomerulonephritis. We have now studied the expression
      of the gene for inducible NO synthase (iNOS) in accelerated nephrotoxic nephritis
      (NTN). The purpose of the study was to confirm in vivo induction of iNOS in this
      model of immune complex disease, and to relate the onset of induction and the
      level of expression to pathogenic events in the model. Glomeruli from rats with
      NTN were isolated at 6 h, 24 h and 2, 4 and 7 days and total RNA extracted. RNA
      (10 micrograms) was reverse transcribed and polymerase chain reaction (PCR) was
      performed with primers homologous to rat vascular smooth muscle iNOS and rat beta
      actin. A 222-base PCR product corresponding to iNOS mRNA was present in all
      experimental animals. iNOS expression was also found in activated macrophages,
      neutrophils and IL-1-stimulated but not unstimulated mesangial cells.
      Quantitative competitive PCR was carried out on glomerular samples using a 514-bp
      mutant of a 735-bp PCR product. iNOS expression was present at low levels in
      normal glomeruli and was markedly enhanced at 6 h after the induction of
      glomerulonephritis and peaked at 24 h. Increased iNOS expression persisted to day
      7. beta actin mRNA levels were similar in all glomerular specimens. This study
      demonstrates that there is in vivo induction of iNOS in immune complex
      glomerulonephritis, corresponding to the generation of nitrite we have previously
      reported. iNOS gene expression is detectable within 6 h of induction of NTN,
      indicating the onset of gene transcription is closely related to the initial
      formation of immune complexes.

PMID- 7519534
TI  - Autoantibodies against a novel DNA-binding protein: DNA-protein interaction as a
      requisite for expression of antigenic reactivity.
AB  - A novel DNA-binding protein complex, the HB complex, has been characterized by
      means of autoantibodies. Three proteins of 9000, 7500, and 7000 Da constitute the
      HB complex. The 9000- and 7500-Da proteins are phosphorylated. Autoantibodies
      recognize the 7000-Da protein when it is bound to DNA. No reactivity against any
      protein was observed when the complex was dissociated from DNA. The three
      proteins are acidic (pI 5-6.2), and the complex was able to bind to synthetic
      double-stranded DNAs of different composition.

PMID- 7519535
TI  - It's not what it seems. The relationship between parents' concerns and children
      with global delays.
AB  - Parents of children with significant behavioral or emotional problems have tended
      to be concerned about their behavior or emotional well-being, whereas parents of
      children with speech-language impairments were more concerned about speech
      language development. The present study was designed to assess whether a parallel
      relationship between type of parental concern and type of developmental problem
      continues when children have global delays. Subjects were 95 parents and their
      children from birth to 6 years of age who attended day-care centers. Parents'
      concerns were categorized into developmental domains. Children were given a
      criterion battery of intelligence and adaptive behavior tests. Global delay was
      identified in 18 children (19%). Concerns about global development were raised by
      only 5% of all parents. Concerns about speech-language and/or behavior were
      sensitive in detecting global deficits (83%), while the absence of such concerns
      had modest specificity in detecting normal development (47%). Parents' concerns
      continue to be useful in prescreening and can identify patients in need of
      further screening. However, pediatricians should anticipate that parents of
      children with global delays may raise concerns, not about global development, but
      rather about behavior/emotional status and/or speech-language skills. The best
      response to such concerns is to administer screening measures which assess
      multiple developmental domains.

PMID- 7519532
TI  - Anticardiolipin antibodies and beta 2-glycoprotein I.

PMID- 7519533
TI  - Persistent reduction of complement receptor 3 alpha-chain expressing mononuclear
      blood cells and transient inhibitory serum factors in Whipple's disease.
AB  - Several small studies have indicated an impaired cell mediated immune response as
      a possible cause for the delayed elimination of the bacteria in Whipple's
      disease. A specific defect, however, has not been defined. We examined the
      expression of cell surface molecules and mitogenic responses of peripheral blood
      mononuclear cells in 27 patients with Whipple's disease at different disease
      stages by indirect immunofluorescence and by measurement of [3H]thymidine
      incorporation, respectively. E-rosette formation and cutaneous reaction to seven
      recall antigens were determined. Matched healthy donors served as controls. We
      found a significantly reduced number of cells expressing the complement receptor
      3 alpha-chain (= CD11b) in all patients. In florid disease, the number of
      activated cells (in particular CD58 positive cells) was increased and CD4/CD8
      ratios were diminished. Proliferation to phytohemagglutinin and to sheep red
      blood cells was reduced at all stages of the disease. Serum of control persons
      reversed this decreased responsiveness especially in patients with active
      disease. Skin reaction was hypoergic in all patients. Determination of CD58
      positive cells increased in patients with active disease may be useful to define
      the activity of the disease and the duration necessary for treatment. Transient
      inhibiting serum activities may impair the CD2/CD58 interaction. The reduction of
      cells expressing CD11b, the decreased proliferation, and the cutaneous hypoergy
      indicate a persisting defect of cell mediated immunity in vivo and in vitro.
      These defects may contribute to the impaired ability of patients with Whipple's
      disease to eliminate bacteria.

PMID- 7519536
TI  - Models of linear and cyclical grief. Different approaches to different
      experiences.

PMID- 7519537
TI  - [Abdominal emergencies in patients with AIDS].
AB  - This is a report on five patients suffering from AIDS who underwent emergency
      abdominal surgery: One patient with gangrenous appendicitis, three with a small
      bowel perforation and a third with a colonic bleeding. The first outlived the
      appendectomy by seven month; the second and the third the small bowel resection
      by eight weeks resp. by 10 weeks. The fourth died four weeks after hemicolectomy
      and a relaparotomy with colonic resection for profuse bleeding. The fifth died
      because of infiltration of the heart by a malignant lymphoma. None of the
      patients developed any complications due to surgery. A review is given on
      emergencies caused by abdominal diseases which a surgeon must be aware of in
      patients with AIDS. The palliative character of surgery in these patients is
      stressed.

PMID- 7519538
TI  - An evaluation of antimicrobial treatment for Whipple's Disease. Tetracycline
      versus trimethoprim-sulfamethoxazole.
AB  - Whipple's disease is a multisystemic disorder in which almost all organ systems
      can be invaded by rod-shaped bacteria. Without extended antimicrobial therapy,
      its course is lethal. Empirically, treatment consists of tetracyclines given for
      one to two years. Trimethoprim-sulfamethoxazole, a compound that crosses the
      blood-brain barrier, has been suggested as an alternative when patients were
      observed with progressive cerebral involvement. There has never been a formal
      evaluation of the selection of antibiotics for the treatment of Whipple's
      disease. In the present nonrandomized, partially retrospective study, we compared
      the result of two treatment regimens in 30 patients, all examined personally.
      Twenty-two patients were treated with tetracycline and eight patients with
      trimethoprim-sulfamethoxazole. In five patients, therapy with tetracycline was
      changed to another antimicrobial agent because of treatment failure or drug
      intolerance. The main treatment measure was disappearance of the clinical
      symptoms such as weight loss, arthritis, malabsorption, fever, edema, central
      nervous system manifestations, lymphadenopathy, and congestive heart failure.
      Drug intolerance requiring a change of medication was also considered a treatment
      failure. We found that trimethoprim-sulfamethoxazole induced complete clinical
      remission in 12 of 13 treatment cycles, tetracycline in 13 of 22 treatment cycles
      (P < 0.05; mean difference 33%; 95% confidence interval 8% to 58%). Trimethoprim
      sulfamethoxazole was also more efficacious than tetracycline in the treatment of
      cerebral Whipple's disease. However, trimethoprim-sulfamethoxazole did not
      prevent cerebral manifestations in all cases. The only deaths due to Whipple's
      disease occurred in patients with cerebral involvement. It is concluded that
      treatment with trimethoprim-sulfamethoxazole was significantly superior to that
      with tetracycline in inducing clinical remission of Whipple's disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7519539
TI  - Demonstration of fibrils in the hyaline globules of yolk sac tumor with parietal
      differentiation in fine-needle aspiration smears.
AB  - Hyaline globules of the yolk sac tumor (YST) have been described as homogeneous
      pink intracellular globules and intercellular basement membrane material [Akhtar
      et al.: Diagn Cytopathol 1990:6:184-192]. In Diff-Quik-stained air-dried smears
      of a lung fine-needle aspiration (FNA) of YST metastatic from anterior
      mediastinum, short curvilinear nonbranching fibrils are demonstrated in the
      metachromatic hyaline substance. The fibril-containing hyaline substance, which
      presents as intracellular globules as well as extracellular matrix deposits, is a
      diagnostic clue for YST with parietal differentiation [Ulbright et al.: Am J Surg
      Pathol 1986; 10:151-164]. The fibrils are not observed in the translucent
      homogeneous golden yellow hyaline substance in the Papanicolaou preparation. The
      fibrils are speculated to be the core protein of proteoglycans. To the best of
      the author's knowledge, this is the first demonstration of fibrils in the hyaline
      substance of YST with parietal differentiation.

PMID- 7519540
TI  - Immunocytochemical typification of mesothelial cells in effusions: in vivo and in
      vitro models.
AB  - We have performed immunocytochemical, immunoelectron microscopy, Western blot,
      and culture techniques using monoclonal antibodies against cytokeratin, vimentin,
      and desmin on 17 benign and 20 malignant effusions of pleural and ascitic origin.
      Triple coexpression of these three antigens was observed in benign reactive
      mesothelial cells as well as in one case of mesothelioma. All metastatic
      adenocarcinoma cells were consistently negative to desmin and positive to
      cytokeratin and vimentin. Present results were helpful to distinguish reactive
      and malignant mesothelioma from metastatic carcinoma cells in effusions.

PMID- 7519542
TI  - Violation of cell lineage restriction compartments in the chick hindbrain.
AB  - Previous cell lineage studies indicate that the repeated neuromeres of the chick
      hindbrain, the rhombomeres, are cell lineage restriction compartments. We have
      extended these results and tested if the restrictions are absolute. Two different
      cell marking techniques were used to label cells shortly after rhombomeres form
      (stage 9+ to 13) so that the resultant clones could be followed up to stage 25.
      Either small groups of cells were labelled with the lipophilic dye DiI or single
      cells were injected intracellularly with fluorescent dextran. The majority of the
      descendants labelled by either technique were restricted to within a single
      rhombomere. However, in a small but reproducible proportion of the cases (greater
      than 5%), the clones expanded across a rhombomere boundary. Neither the stage of
      injection, the stage of analysis, the dorsoventral position, nor the rhombomere
      identity correlated with the boundary crossing. Judging from the morphology of
      the cells, both neurons and non-neuronal cells were able to expand over a
      boundary. These results demonstrate that the rhombomere boundaries represent cell
      lineage restriction barriers which are not impenetrable in normal development.

PMID- 7519541
TI  - [Severe pancytopenia in old age after 12-month ACE inhibitor therapy].
AB  - A sprightly 79-year-old woman was treated for high blood pressure with indapamide
      (2.5 mg/day) and the angiotensin converting enzyme (ACE) inhibitor lisinopril (5
      mg/day). About 12 months after starting treatment a blood count carried out
      because of a syncopal attack revealed pancytopenia (haemoglobin 3.3 g/dl,
      erythrocytes 1.0 x 10(6)/microliters, leucocytes 1100/microliters, platelets
      8000/microliters). Until then the blood count had been unremarkable. The bone
      marrow showed severe hypoplasia of all three cell lines with reactive
      plasmocytosis. Malignant cells were not present. The patient received a total of
      nine units of erythrocytes and seven units of platelets. Her care included
      reverse barrier nursing and antibiotic treatment. She was also given high dose
      steroid therapy (methylprednisone up to 150 mg/day) and granulocyte colony
      stimulating factor (filgrastim 300 micrograms/day subcutaneously for 25 days),
      and after a latent period of several weeks juvenile myeloid precursors reappeared
      in the blood. Before discharge from hospital the results rose to subnormal levels
      without further transfusions (haemoglobin 8.5/dl, erythrocytes 3.1 x
      10(6)/microliters, leucocytes 3900/microliters, platelets 21.000/microliters). In
      the bone marrow, all three cell lines were beginning to recover. The final
      diagnosis was incompletely reversible pancytopenia resulting from secondary
      aplastic anaemia during ACE inhibitor therapy.

PMID- 7519543
TI  - Negative regulation of the P0 gene in Schwann cells: suppression of P0 mRNA and
      protein induction in cultured Schwann cells by FGF2 and TGF beta 1, TGF beta 2
      and TGF beta 3.
AB  - During the development of peripheral nerves, Schwann cells are induced to form
      myelin sheaths round the larger axons. This process involves a complex series of
      events and the nature of the molecular signals that regulate and control myelin
      formation in Schwann cells is not well understood. Our previous experiments on
      rat Schwann cells in vitro, using serum-free defined medium, showed that a myelin
      related protein phenotype could be induced in early postnatal Schwann cells in
      culture by elevation of intracellular cyclic AMP levels in the absence of growth
      factors, conditions under which the cells are not dividing. Cells with this
      phenotype expressed the major myelin glycoprotein P0 and expression of p75 NGF
      receptor, N-CAM, GFAP and A5E3 proteins was down-regulated. These changes are all
      characteristics associated with myelination in vivo. In contrast, when cyclic AMP
      levels were elevated in the presence of serum, suppression of cyclic AMP-induced
      differentiation resulted and DNA synthesis was induced. In this paper, we have
      used this model system and extended our analysis to explore the relationship
      between defined growth factors and suppression of myelination. We have used pure
      recombinant growth factors normally present in peripheral nerves, i.e. FGF1 and
      FGF2 and TGF beta 1, TGF beta 2, and TGF beta 3 and shown that, like serum, they
      can strongly suppress the forskolin-mediated induction of the P0 gene, both at
      the level of mRNA and protein synthesis. For both growth factor families, the
      suppression of P0 gene expression is dose-dependent and takes place in serum
      starved cells that are mitotically quiescent. In the case of FGF2, however, even
      more complete suppression is obtained when the cells are simultaneously allowed
      to enter the cell cycle by inclusion of high concentrations of insulin in the
      culture medium. The present results raise the possibility that, in addition to
      the positive axonal signals that are usually envisaged to control the onset of
      myelination, growth factors present in the nerve may exert negative regulatory
      signals during development and thus help control the time of onset and the rate
      of myelination in peripheral nerves.

PMID- 7519544
TI  - The effects of a pulsed application of chlorpyrifos on macroinvertebrate
      communities in an outdoor artificial stream system.
AB  - The results of an experiment examining the effects of pulsed application of a
      pesticide, chlorpyrifos, in an outdoor replicated artificial stream system are
      described. Two levels of chlorpyrifos were used, 0.1 microgram.liter-1 (low dose)
      and 5.0 micrograms.liter-1 (high dose), and applied for 6 hr. Low-dose streams
      showed little impact from the treatment and were indistinguishable from control
      streams. Significant reductions in invertebrate density occurred in the high-dose
      streams and were mainly due to reductions in density of chironomid larvae. There
      were no significant reductions in taxon richness associated with the treatments
      indicating no localized extinctions of species. Diversity measures were
      insensitive to the changes observed in the streams. Ordination and classification
      procedures were more illuminating and indicated that the major effect of
      pesticide application was to interfere with the normal pattern of community
      change occurring within the system. Recovery following treatment was rapid. The
      results are discussed with reference to the use of indicator species and
      biological monitoring strategies intended to identify human-mediated disturbance.

PMID- 7519545
TI  - Impact of low-level sampling stress on interpretation of physiological responses
      of white sucker exposed to effluent from a bleached kraft pulp mill.
AB  - In this study the authors evaluated the effects of handling and confinement
      stress on a number of biochemical parameters in prespawning male white sucker
      collected from a bleached kraft mill effluent (BKME) exposed and a reference
      site. There were no effects of site or stress level on plasma cholesterol or
      glutamic oxalacetic transaminase activity; all other parameters were affected by
      either sampling stress or overnight confinement. Unstressed BKME fish reflected
      higher levels of plasma lactate, and lower levels of plasma testosterone, 17
      alpha,20 beta-dihydroxy-4-pregnen-3-one, and cortisol. Acute handling stress or
      overnight confinement created a site difference in plasma glucose, protein, and
      11-ketotestosterone, reversed the site effect for plasma lactate, and eliminated
      site differences for 17 alpha,20 beta-dihydroxy-4-pregnen-3-one. Since it is very
      difficult to standardize capture and handling stress in field studies impacted by
      industrial effluents, biochemical differences must be interpreted carefully. This
      study has also demonstrated for the first time that BKME exposure resulted in
      reduced circulating levels of the stress steroid cortisol, similar to the
      decreases in reproductive sex steroids previously reported.

PMID- 7519548
TI  - Classification of biodegradability by growth kinetic parameters.
AB  - On the basis of classical Monod equations for microbial growth, kinetic parameter
      values are assessed to enable the characterization of biodegradability as a
      substance property. Although growth is a microbial property, the substance
      selects those species from a mixed inoculum that can profit at most under the
      prevailing conditions. Hence it is concluded that the combination of observed
      cell yield Y approximately 0.5 g solids/g COD, maximum growth rate mu max >
      0.3/day, and half-saturation constant Ks < 0.6 mg COD/liter provides a suitable
      set of borderline criteria for classification of chemicals as readily
      biodegradable. Of these parameters mu max is suitable for differentiating
      chemicals, whereas Y seems more or less equal for all readily degradable
      substances and Ks is not easily measurable with existing standard test methods.
      In this approach the density of specific microbes in the inoculum or during the
      test is excluded from the substance characterization and thus adaptation
      phenomena have no influence. From correlation studies and model calculations it
      can be expected that if the above parameters are estimated on the basis of
      standard tests for ready biodegradability, these tests will not produce false
      positives. Provided that the above parameters can be estimated, any other method
      than just the standard methods can be used to classify a substance as readily
      biodegradable.

PMID- 7519547
TI  - The effects of hedges on spray deposition and on the biological impact of
      pesticide spray drift.
AB  - Two series of drift deposition measurements were carried out at different wind
      speeds using sodium fluorescein as a tracer dye sprayed over a grass field 6 m
      upwind of a hedge. Efficient receptors were placed below and above hedge height
      (1.6 m) between 1 and 20 m downwind from the sprayed area. Receptors below hedge
      height reflected a sudden decrease in deposition immediately behind the hedge,
      followed by a gradual increase again up to 15 m, i.e., nine times the height of
      the hedge. The sheltering effect of a hedge from the biological impact of spray
      drift was studied by bioassays using tomato and Lychnis flos-cuculi plants for
      the herbicide MCPA and young Pieris brassicae larvae for the insecticide
      cypermethrin. These demonstrated that the protection afforded to sensitive
      species in strong winds may be quite limited, and severe damage may be inflicted
      over considerable distances. In intermediate cases, a protected zone is followed
      by a zone of further significant damage before drift depositions cease to have
      further effect. In some cases, the sheltered zone may extend to a distance where
      drift deposition, even in the absence of a hedge, has minimal effect.

PMID- 7519546
TI  - Cytochrome P450-dependent enzymes and oxidant-mediated responses in rainbow trout
      exposed to contaminated sediments.
AB  - Hatchery-reared immature rainbow trout (Oncorhynchus mykiss) were exposed to
      different concentrations (2 and 4 liters) of contaminated sediment taken from a
      site receiving unbleached pulp mill effluents. The fish were held in aquaria and
      sampled three times during an experimental period of 21 days. The monooxygenase
      activity, measured as the deethylation of 7-ethoxyresorufin (EROD activity),
      increased three- to fourfold in the exposed fish relative to controls. The
      increase was not dependent on exposure concentration. Cytochrome P450IA1, the
      EROD catalyst, demonstrated proportional induction in the 2-liter exposed fish.
      However, exposure to 4 liters sediment strongly induced P450IA1 and did not
      reflect EROD activity. This may suggest inhibition of P450IA1 activity by the
      amount of chemicals discharged from pulp mills. UDPglucuronosyltransferase
      increased at one stage of the experimental period, while glutathione S
      transferase remained unchanged. Amounts of total glutathione in blood, liver, and
      muscle were slightly increased by exposure to contaminated sediments, but hepatic
      enzyme activities of superoxide dismutase and catalase were not affected. In
      conclusion, monooxygenase activities appear to be a sensitive tool in the
      monitoring of sediment toxicity.

PMID- 7519549
TI  - Extrapolation of biodegradability test data by use of growth kinetic parameters.
AB  - Formulas for extrapolation of test data on biodegradability to percentage removal
      in treatment plants and biological half-life time in surface water are derived
      from growth kinetics. A pseudo-first-order rate constant can be used provided
      that substance properties and microbial density in the environment are assessed
      independently. For comparison of kinetics at different concentration levels an
      extrapolation factor can be used that is based on the ratio between maximum
      growth rate and sludge age in a treatment plant. The specific microbial density
      is estimated on the basis of proportional growth on all degradable substances in
      a state of equilibrium after adaptation. As a consequence the percentage removal
      can be predicted on the basis of sludge age and influent concentration in
      combination with the substance properties. The formulas predict that the
      combination of sewage treatment and surface water gives an almost equal
      biological half-life time for all readily biodegradable substances in the surface
      water. The predicted removal percentages and biological half-life times are in
      agreement with observations.

PMID- 7519551
TI  - Effects of lindane exposure on rainbow trout (Oncorhynchus mykiss) immunity. III.
      Effect on nonspecific immunity and B lymphocyte functions.
AB  - The effect of the organochlorine insecticide lindane (gamma
      hexachlorocyclohexane) was examined on some major immune functions of rainbow
      trout (Oncorhynchus mykiss) on the chemiluminescent response of pronephric cells
      (PMA-induced) in phagocytosis, on the proliferation of lymphocytes with B and T
      mitogens, and on the number of B lymphocytes analyzed by cytofluorometry. Two
      different methods of exposure were tried via food (first protocol) and via a
      single intraperitoneal injection (second protocol). After the oral contamination
      at a daily body dose of 1 mg/kg for 30 days, a decreased chemiluminescent
      response was observed with persisted for two more weeks and disappeared over 1.5
      months. No effect was observed on lymphocyte proliferation and on the number of
      circulating B lymphocytes. In the second protocol lindane was administered
      intraperitoneally at 10, 50, or 100 mg/kg body wt. After 45 days the lymphocyte
      proliferation of B cells was depressed but not the T cell one. The B cells number
      in head kidney as measured by cytofluorometry was not significantly modified.
      Some nonspecific immunity parameters in sera were significantly modified.

PMID- 7519552
TI  - Strategies employed to determine the acute aquatic toxicity of ethyl benzene, a
      highly volatile, poorly water-soluble chemical.
AB  - Studies are described in which ethyl benzene (EB) was tested to determine its
      acute toxicity to three marine organisms, Atlantic silversides (Menidia menidia),
      mysid shrimp (Mysidopsis bahia), and diatoms (Skeletonema costatum), and to one
      freshwater algae (Selenastrum capricornutum). The respective 96-hr median lethal
      concentration (LC50) values and 95% confidence intervals for EB in the flow
      through studies with fish and mysid shrimp were 5.1 (4.4-5.7) mg/liter and 2.6
      (2.0-3.3) mg/liter. While the 96-hr median effective concentrations (EC50's) for
      growth inhibition and 95% confidence intervals for the static studies with
      diatoms and algae were 7.7 (5.9-10.0) mg/liter and 3.6 (1.7-7.6) mg/liter,
      respectively. Problems were encountered in all four studies as a result of the
      high volatility and poor water solubility of EB in water and an apparent "salting
      out" effect noted in seawater. This effect was found particularly true in the
      diatom and algae studies where the salinity was increased with the addition of
      culture medium. Measures are described which were used to overcome this stability
      problem with EB. These included sealing the test systems tight without any air
      spaces to prevent the collection of EB vapors. Also, increased mixing of EB in
      the test solutions was found to be essential in the flow-through studies to
      maintain stable levels. In the case of the diatom and algal studies, since
      current EPA test guidelines were judged to be inadequate to overcome EB
      volatility from the test medium, a new closed test system had to be developed and
      employed, after validation with a nonvolatile reference toxicant in the new and
      conventional static test systems. The results of these studies indicate that
      previous reports underestimated the potential acute aquatic toxicity of EB by at
      least one order of magnitude. The implications of these findings are discussed in
      relation to the potential environmental impact of EB and the resultant regulatory
      actions.

PMID- 7519550
TI  - Effects of lindane exposure on rainbow trout (Oncorhynchus mykiss) immunity. II.
      In vitro restoration of antibody-secreting cells and lymphocyte proliferation
      activity by nitrogranulogen after in vivo immunosuppression due to lindane.
AB  - A dose-dependent immunomodulatory effect of Nitrogranulogen (NGG) was observed in
      vitro on antibody-secreting cells and lymphocyte proliferation in rainbow trout.
      Because different doses of lindane (10, 50 and 100 mg/kg, injected
      intraperitoneally) had a depressing effect on the same immune functions, the
      authors restored them using NGG in vitro.

PMID- 7519555
TI  - Discordance between four second-generation enzyme immunoassay kits in anti
      hepatitis C virus screening. The Study Group of the Laboratoires de Virologie des
      Centres Hospitaliers Universitaires francais.

PMID- 7519556
TI  - Large platelets continue to circulate in an activated state after myocardial
      infarction.
AB  - This study was intended to investigate the actual platelet activation status
      after an acute coronary event. The activation status of circulating platelets was
      assayed directly by measuring the membrane activation markers CD62 and CD63 with
      the Dusseldorf III flow cytometry test in 22 patients with the diagnosis of acute
      myocardial infarction during the 48-h observation period following the acute
      event. The number of activated, marker-positive sample platelets was
      significantly increased in the post-MI patients: CD62: 5.8% x 2.25 +/- 1 vs. 3.5%
      x 2.32 +/- 1, P < or = 0.05; CD63: J8.7% x 1.77 +/- 1 vs. 4.6% x 2.16 +/- 1, P <
      or = 0.00.1. The platelet volume and count were concomitantly increased (12.1 +/-
      2.4 fl/ 236 +/- 90 x 10(3) microliters-1 compared to 8.3 +/- 1.6 fl/ 187 +/- 42 x
      10(3) microliters-1) in the control group. Particularly large platelets were
      identified as being activated documented by the exponential increase in the
      difference in CD63-binding sites per sample platelet above the 90%-percentile and
      below the 10%-percentile of the volume distribution: delta + 1341 +/- 903 (MI
      patients) vs. delta + 276 +/- 126 (controls), P < or = 0.00.1. Significant
      creatine kinase elevation and decrease in platelet count was found in the non
      survivor subset (n = 5). We conclude that predominantly large platelets continue
      to circulate in an activated state after MI. This study provides direct evidence
      that the assumption of an increased thrombotic potential becomes operative in
      vivo in MI patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519553
TI  - Detection of genotoxic effects in human gastric and nasal mucosa cells isolated
      from biopsy samples.
AB  - To assess genotoxic burdens from chemicals, it is necessary to relate
      observations in experimental animals to humans. The success of this extrapolation
      would be increased by including data on chemical activities in human tissues.
      Therefore, we have developed techniques to assess DNA damage in human gastric and
      nasal mucosa (GM, NM) cells. Biopsy samples were obtained during gastroscopy from
      macroscopically healthy tissue of the stomach or from healthy nasal epithelia
      during surgery. The specimens were incubated for 30-45 min at 37 degrees C with a
      digestive solution. We obtained 1.5-8 x 10(6) GM cells and 5-10 x 10(5) NM cells
      per donor, both with viabilities of 80-95%. The cells were incubated in vitro for
      1 hr at 37 degrees C with the test compounds added in their appropriate solvents.
      In GM cells, we studied N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), sodium
      dichromate (Na2Cr2O7), nickel sulphate (NiSO4), cadmium sulphate (CdSO4), and
      lindane. In NM cells, lindane was investigated. Each compound was assessed for
      DNA damaging activity in cells of at least three different human donor samples
      using the microgel single cell assay. Similar studies were performed with GM and
      NM cells obtained from Sprague-Dawley rats. We have found human GM cells to be
      more sensitive to the genotoxic activity of MNNG than rat GM cells (low effective
      concentration [LEC] = 0.16 and 0.625 micrograms/ml for human and rat,
      respectively). Human cells were also more sensitive to the cytotoxic/genotoxic
      activity of NiSO4 (LEC = 5 and 19 mumoles/ml for human and rat, respectively).
      CdSO4 was genotoxic in human GM cells (LEC = 0.03-0.125 mumoles/ml), whereas no
      dose-related genotoxicity was observed in rat GM at concentrations up to 0.5
      mumoles/ml. In contrast, approximately equal responses regarding genotoxicity and
      cytotoxicity were observed in rat and human GM for Na2Cr2O7 (0.25-1 mumoles/ml).
      Lindane, however, was genotoxic in three out of four rat GM but not in human GM
      cells (0.5-1 mumoles/ml), whereas it was active in both rat and human NM cells.
      Together with other recently published in vivo findings, our results with lindane
      can be interpreted according to a parallelogram approach. In view of possible
      human exposure situations and the sensitivities of the two target tissues from
      both species, the data imply that lindane will pose a health risk to humans by
      inhalation but not by ingestion.

PMID- 7519554
TI  - Metabolic response to lower abdominal surgery: analgesia by epidural blockade
      compared with intravenous opiate infusion.
AB  - To determine whether the type of peri-operative analgesic regimen affects the
      metabolic response during and after surgery, we studied 19 women undergoing
      abdominal hysterectomy under propofol anaesthesia. Patients were randomized to
      receive either continuous intravenous opioid or a bupivacaine-opioid mixture
      through a lumbar epidural catheter. Total body oxygen consumption and carbon
      dioxide excretion, blood glucose and haemodynamic variables were determined up to
      24 h after surgery. No differences in any metabolic or haemodynamic variables
      were noted during surgery. In the post-operative period, the increase in oxygen
      consumption up to pre-operative values, the urinary nitrogen excretion and the
      changes in acute phase proteins were similar in both treatment groups. In
      contrast, the respiratory quotient was significantly higher in the lumbar
      epidural group than in the intravenous opioid group, 0.87 (SD 0.04) vs 0.77 (SD
      0.06) (P < 0.05) and the hyperglycaemic response was more delayed in the epidural
      group. These data suggest that prolonged sympathetic blockade associated with
      epidural analgesia might contribute to better preservation of glucose homeostasis
      in the perioperative period.

PMID- 7519557
TI  - Delayed gastric emptying induced by inhibitors of nitric oxide synthase in rats.
AB  - The effect of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine
      methyl ester, on gastric emptying of a non-nutrient solution was investigated in
      conscious rats. NG-Monomethyl-L-arginine (10 mg/kg i.v.) and NG-nitro-L-arginine
      methyl ester (3 or 10 mg/kg i.v.) inhibited the 20-min rate of gastric emptying
      of liquids by 34%, 69% and 84% respectively, whereas the 0.3 mg/kg of NG-nitro-L
      arginine methyl ester or 3 mg/kg of NG-monomethyl-L-arginine had no effect. The
      inhibitory effect of NG-nitro-L-arginine methyl ester (3 mg/kg) was prevented by
      L-arginine (300 mg/kg i.v.), but not by D-arginine (300 mg/kg i.v.). NG-Nitro-L
      arginine methyl ester (0.3-10 mg/kg) induced a dose-related increase in mean
      blood pressure up to 161 +/- 10 mm Hg. Spontaneous hypertensive rats with a mean
      blood pressure of 180 +/- 5 mm Hg had a gastric emptying rate of 51.9 +/- 6.1%.
      These data indicate that NO synthase inhibitors given i.v. at doses that inhibit
      NO synthase, delay gastric emptying through mechanisms which are unrelated to
      changes in arterial blood pressure.

PMID- 7519559
TI  - Effects of neuropeptide Y on lung vascular permeability in the pulmonary
      circulation of rats.
AB  - The effects of neuropeptides on the capillary filtration coefficient in the
      vessels of the pulmonary circulation were examined, using isolated lung perfusion
      preparations from rats. Neuropeptide Y and neurokinin A elevated the filtration
      coefficient, and calcitonin gene related peptide diminished it. Neurotensin and
      substance P did not affect the value at concentrations less than 10(-7) M. The
      number of extravasated carbon particle deposits subsequent to tracheal
      application of neuropeptide Y during spontaneous respiration increased in a dose
      dependent manner. From these results, we conclude that neuropeptide Y may
      increase vascular permeability in the pulmonary circulation.

PMID- 7519558
TI  - Effects of nifedipine and Bay K 8644 on contractile activities in single skeletal
      muscle fibers of the frog.
AB  - The effects of dihydropyridine derivatives on contractile activity were examined
      in single fibers of frog skeletal muscles. Both nifedipine and Bay K 8644
      enhanced twitch responses regardless of the presence or absence of Ca2+ without
      any effects on the resting membrane potential, evoked action potential and Ca2+
      sensitivity of the contractile machinery. Twitch responses enhanced by Bay K
      8644, but not by nifedipine, were partially reduced by adenine, an inhibitor of
      Ca(2+)-induced Ca2+ release from sarcoplasmic reticulum, suggesting the
      involvement of Ca(2+)-induced Ca2+ release in Bay K 8644-induced potentiation of
      the twitches. Both nifedipine and Bay K 8644 caused a dose-dependent potentiation
      of K+ contractures without any effects on the membrane potential in the presence
      of Ca2+, but inhibited the contractures in the absence of Ca2+. These results
      suggest that dihydropyridine derivatives modify contractile activities of
      skeletal muscles by modulating the dihydropyridine receptors on the surface of T
      tubules acting as voltage sensors.

PMID- 7519560
TI  - Preferential inhibition of inducible nitric oxide synthase by ebselen.
AB  - Ebselen, 2-phenyl-1,2-benzisoselenazole-3(2H)-one can preferentially inhibit the
      activity of inducible nitric oxide (NO) synthase with little inhibition of
      endothelial constitutive NO synthase within a certain concentration range. This
      suggests that ebselen deserves further in vivo studies to examine its possible
      application to the therapy of septic shock where inducible NO synthase is
      responsible for vasodilation.

PMID- 7519561
TI  - Protein kinase C and protein kinase A regulate the expression of angiotensin II
      receptor mRNA in smooth muscle cells.
AB  - Using reverse transcription polymerase chain reaction and fura-2 microfluorometry
      of intracellular Ca2+ concentrations, we investigated the effects of angiotensin
      II and cyclic AMP on the expression of angiotensin II type 1 receptor mRNA and
      the relationship between angiotensin II receptor mRNA level and physiological
      responsiveness in rat aortic smooth muscle cells in primary culture. Angiotensin
      II (1 microM) induced a time- and dose-dependent transient decrease in the level
      of angiotensin II receptor mRNA. The maximal decrease (50 +/- 13% of control)
      occurred at 6 h, followed by a gradual return to the control level within 24 h. H
      7 (30 microM), a relatively specific protein kinase C inhibitor, inhibited
      decrease in the expression of angiotensin II receptor mRNA induced by 6 h
      angiotensin II treatment, while 6 h stimulation by 0.3 microM phorbol 12
      myristate 13-acetate also induced a decrease (35 +/- 8% of control) in the
      expression of angiotensin II receptor mRNA. An increase in cellular cyclic AMP
      induced by 10 microM forskolin plus 10 microM 3-isobutyl-1-methyl-xanthine,
      decreased the angiotensin II receptor mRNA level to 50 +/- 13% of the control at
      6 h and increased it to 219 +/- 39% of the control at 48 h of treatment.
      Angiotensin II-induced decrease and cyclic AMP-induced increase in the expression
      of angiotensin II receptor mRNA were accompanied by a reduction and enhancement
      in [Ca2+]i transients induced by angiotensin II, respectively. In contrast with
      angiotensin II receptor mRNA level (102 +/- 8% of control), the [Ca2+]i
      transients were markedly decreased in angiotensin II plus H-7 treated
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519562
TI  - Basal and acidic fibroblast growth factor-induced atrial natriuretic peptide gene
      expression and secretion is inhibited by staurosporine.
AB  - We examined the mechanisms involved in the activation of atrial natriuretic
      peptide (ANP) gene expression and secretion in response to acidic fibroblast
      growth factor (aFGF) by studying the effects of staurosporine, a protein kinase C
      inhibitor, and 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of
      protein kinase C, on basal and AFGF-induced ANP messenger RNA (mRNA) and
      immunoreactive ANP (IR-ANP) levels in cultured neonatal rat cardiac myocytes.
      Acidic FGF caused a dose- and time-dependent increase in IR-ANP and
      immunoreactive N-terminal fragment of proANP (IR-NT-proANP) release into the
      culture medium from ventricular but not from atrial myocytes. In ventricular
      cells, 50 ng/ml aFGF for 24 or 48 h resulted in a 70% or 181% increase,
      respectively, in the accumulation of IR-ANP into the culture medium. Acidic FGF
      also stimulated ANP gene expression significantly; after 48 h of incubation, the
      ANP mRNA levels of aFGF-treated ventricular myocytes were 205% (P < 0.001) higher
      than those of control cells. Staurosporine alone at concentration of 10 nM
      significantly decreased the basal IR-ANP and IR-NT-proANP secretion, and
      inhibited the aFGF-induced increase in ANP mRNA and IR-ANP levels in ventricular
      myocytes. TPA (100 nM) alone significantly stimulated ANP gene expression and
      secretion but these effects were not augmented by combining aFGF with TPA. High
      performance liquid chromatographical analysis showed that atrial and ventricular
      myocytes maintained in serum-free medium were capable of secreting processed,
      ANP99-126 sized material, and that aFGF did not alter the processing of ANP in
      ventricular cultures. These results demonstrate that aFGF is a potent stimulator
      of ANP gene expression and secretion in cultured neonatal rat ventricular but not
      in atrial cells. The observations that (a) staurosporine completely abolished the
      effects of aFGF on ANP gene expression and release and (b) ANP secretory and gene
      expression inducing effects of phorbol ester were not augmented by aFGF, suggest
      an important role of protein kinase C in mediating aFGF-induced ANP gene
      expression and secretion.

PMID- 7519563
TI  - Activation of 72-kDa type IV collagenase/gelatinase by normal fibroblasts in
      collagen lattices is mediated by integrin receptors but is not related to lattice
      contraction.
AB  - The matrix metalloproteinase 72-kDa type IV collagenase (also known as gelatinase
      A) is thought to be involved in both normal connective tissue remodeling and
      invasive pathological processes. Like other matrix metalloproteinases, 72-kDa
      type IV collagenase is secreted by fibroblast monolayers as an inactive
      proenzyme, but is unique among this enzyme family in that it is not activated by
      serine proteinases such as plasmin. However, when fibroblasts are cultured in a
      collagen lattice, a situation thought to better approximate in vivo conditions,
      we have invariably found much of the secreted 72-kDa type IV collagenase in its
      enzymatically active 62-kDa form. Although collagen lattice contraction appeared
      to be required for the activation of 72-kDa type IV collagenase, we have found
      that the process of contraction can be dissociated from proenzyme activation.
      Both cytochalasin D and alpha-methylmannoside completely blocked lattice
      contraction, but not proenzyme activation. Furthermore, the monoclonal antibody M
      13, which is directed against the beta 1 integrin chain, blocked collagen lattice
      contraction but not 72-kDa type IV procollagenase activation. At concentrations
      significantly higher than required to block lattice contraction or cell adhesion
      to collagen, M-13 was able to inhibit proenzyme activation. A second monoclonal
      antibody to the beta 1 integrin, P5D2, had little effect on collagen lattice
      contraction at low concentrations, but could significantly inhibit the activation
      of 72-kDa type IV procollagenase. Antibodies to the integrin alpha 2 chain also
      inhibited proenzyme activation. These data show that the activation of 72-kDa
      type IV collagenase proenzyme, like collagen lattice contraction, is mediated by
      beta 1 integrin receptors, possibly alpha 2 beta 1. Although both anti-beta 1
      antibodies used are directed to the same site on the integrin chain, the fact
      that each antibody preferentially blocks a different event, either lattice
      contraction or activation of 72-kDa type IV collagenase, suggests the existence
      of branch points in the receptor-mediated signal transduction pathway.

PMID- 7519564
TI  - Ability of insulin and DsRNA to induce interferon system and Hsp 70 in fibroblast
      and epithelial cells in relation to their effects on cell growth.
AB  - We have examined the ability of insulin and dsRNA, a well-known interferon
      inducer, in relation to their effects on cell growth, to induce the expression of
      hsp 70 and the synthesis of interferon in epithelial HT-29 and fibroblast Madin
      Darby bovine kidney (MDBK) cells. Insulin was mitogenic in both MDBK and HT-29
      cells; MDBK cells nevertheless required much higher concentrations. DsRNA
      stimulated the growth of MDBK but inhibited that of HT-29 cells. Both substances
      induced a transient synthesis of hsp 70 in HT-29 and MDBK cells with similar
      kinetics. However, whereas both insulin and dsRNA efficiently induced 2'5'
      oligoadenylate synthetase and an antiviral state through interferon synthesis in
      HT-29 cells, only dsRNA caused these effects in MDBK cells. Thus, insulin cannot,
      unlike dsRNA, elicit an antiviral state in all cell systems, although, like
      dsRNA, it can induce hsp 70, thereby suggesting the cell specificity of insulin
      action. These results reveal that the mitogenic and IFN-inducing effects of
      insulin and dsRNA are dependent on the cell type and unrelated to hsp 70
      expression.

PMID- 7519565
TI  - Coculture inserts possess an intrinsic ability to alter growth regulation of
      human breast cancer cells.
AB  - Coculture systems are used for a wide variety of cell-cell communication studies.
      The results reported here reveal that the microporous polycarbonate membranes
      used in the coculture inserts can remove inhibitory biological macromolecules,
      resulting in increased cell growth. This provides a cautionary tale to all who
      use such coculture systems. For estrogen-sensitive breast cancer cells, the use
      of such membranes results in an increased growth in the absence but not in the
      presence of estradiol. These effects occurred reproducibly both in the presence
      of serum and in serum-free medium. Using MCF7 McGrath human breast cancer cells,
      the up-regulation of basal cell growth in the presence of the coculture insert
      and serum could be reduced upon blockade of the type I insulin-like growth factor
      receptor. Ligand blotting experiments revealed that these insert membranes could
      bind out insulin-like growth factor binding proteins (IGFBP) and remove IGFBP
      from the culture medium. This suggests a role for IGFBP in the regulation of MCF7
      breast cancer cell growth. The molecular and clinical implications are discussed.

PMID- 7519566
TI  - Schistosoma mansoni: characterization of sequence variants of the 28-kDa
      glutathione S-transferase.

PMID- 7519567
TI  - Effects of chlormadinone acetate, acetazolamide and oxygen on awake and asleep
      gas exchange in patients with chronic obstructive pulmonary disease (COPD).
AB  - The purpose of this study was to assess the short-term effects of chlormadinone
      acetate (CMA), a synthetic progestogen, acetazolamide (ACET) and oxygen on awake
      and asleep blood gas values. The study was conducted according to a randomized,
      double-blind and placebo-controlled design in 53 hypoxaemic patients with chronic
      obstructive pulmonary disease. On the first two consecutive nights, all patients
      received either room air or oxygen, via a nasal cannula, in random order. They
      then received either CMA (25 mg), ACET (250 mg) or placebo twice a day, all in
      identical capsules. On the third study night, after one week of drug treatment,
      the patients were tested breathing room air. CMA and ACET therapy decreased mean
      daytime arterial carbon dioxide tension (PaCO2) by 0.7 and 0.5 kPa, respectively,
      and night-time end-tidal carbon dioxide tension (PETCO2) by 0.5 and 0.3 kPa,
      respectively. Supplemental oxygen caused increased CO2 retention during the day
      and night (0.6 and 0.3 kPa, respectively. Daytime arterial oxygen tension (PaO2)
      increased to the same extent during ACET (1.9 kPa) and oxygen (2.5 kPa). Asleep
      oxygen saturation improved most with oxygen supplementation (7%), although ACET
      also caused significant improvement (4%). CMA administration had virtually no
      effect on mean awake and asleep hypoxaemia. ACET therapy significantly improved
      subjective sleep quality. On CMA, minute ventilation increased in association
      with an augmentation of the hypercapnic ventilatory response. ACET treatment
      increased both hypercapnic and hypoxic ventilatory responses. We conclude from
      the group of patients with COPD studied, that the short-term effects of ACET
      treatment on gas exchange compare favourably with those of CMA. Oxygen therapy
      improves oxygenation slightly more than ACET, but aggravates CO2 retention.

PMID- 7519568
TI  - Production and characterization of monoclonal antibodies specific to multi
      ubiquitin chains of polyubiquitinated proteins.
AB  - Polyubiquitinated proteins tagged with multi-ubiquitin chains are substrates
      preferred by the 26 S proteasome (a ubiquitin/ATP-dependent proteolytic complex).
      Here, we developed a simple method for the efficient preparation of
      polyubiquitinated proteins which are degraded by the 26 S proteasome in an ATP
      dependent manner. Our efficient method enabled us to produce ten monoclonal
      antibodies that recognized the multi-ubiquitin chains of the polyubiquitinated
      proteins, but not free ubiquitin or the protein moieties. Eight of the antibodies
      recognized only the multi-ubiquitin chains of the polyubiquitinated proteins,
      while the other two antibodies cross-reacted with mono-ubiquitin and methyl
      ubiquitin, both of which are linked to proteins via an isopeptide bond, as well
      as with the multi-ubiquitin chains. Thus these antibodies are novel and useful
      tools for the identification and quantification of polyubiquitinated proteins in
      various cells and tissues under physiological and pathological conditions.

PMID- 7519569
TI  - Influence of the conformation of a macromolecule on the generation of T-cell
      proliferative response. A study with model polypeptides.
AB  - To study the influence of the conformation of polypeptidic macromolecules on the
      generation of T-cell epitopes, sequential polypeptides with an octamer repeat
      unit were designed and synthesized. They adopt mainly unordered and alpha-helical
      conformations. Among these polypeptides, those containing proline are fully or
      partly unordered, and are more effective at inducing T-cell proliferation than a
      proline-free very stable alpha-helical polypeptide. This extremely stable alpha
      helical conformation, probably stabilized by aggregation, would enhance its
      stability against proteolytic processing.

PMID- 7519570
TI  - Minor neurological dysfunction and quality of movement in relation to neonatal
      cerebral damage and subsequent development.
AB  - Minor neurological dysfunction (MND) and quality of movement were studied in
      relation to neonatal cerebral damage and developmental assessments at 3 1/2 years
      of age in 66 very low-birthweight children without obvious disability. MND was
      found in 19 children and was significantly related to the quality of movement.
      The results demonstrate that MND is associated with neonatal cerebral damage at
      preschool-age, but that the assessment of quality of movement is associated with
      more complex sensory motor tasks and simultaneous processing. At preschool-age,
      quality of movement might therefore be a better marker of later learning problems
      than traditional signs of minor neurological dysfunction.

PMID- 7519571
TI  - Does the loss of placental hormones contribute to neurodevelopmental disabilities
      in preterm infants?

PMID- 7519572
TI  - Comparative toxicities of o-, m-, and p-nitrotoluene in 13-week feed studies in
      F344 rats and B6C3F1 mice.
AB  - Nitrotoluenes are high-production-volume chemicals used in the synthesis of
      agricultural chemicals and in various dyes. Because of differences in the
      metabolism of the three isomers and their capabilities to bind to DNA,
      comparative toxicity studies of o-, m-, and p-nitrotoluene were conducted in F344
      rats and B6C3F1 mice. o-, m-, or p-Nitrotoluene was administered in the feed to
      male and female rats and mice at doses ranging from 625 to 10,000 ppm for 13
      weeks. These doses delivered approximately 40 to 700 mg/kg body wt/day for rats
      and 100 to 1700 mg/kg/day for mice. There were no treatment-related effects on
      survival in any of the studies. Decreased body weights relative to controls
      occurred in dosed rats and mice in all studies at the higher dose levels and were
      most pronounced in rats receiving o-nitrotoluene. Mesotheliomas of the tunica
      vaginalis were observed in 3 of 10 male rats receiving o-nitrotoluene at 5000
      ppm, and mesothelial cell hyperplasia was observed in 2 of 10 male rats receiving
      o-nitrotoluene at 10,000 ppm. Kidney toxicity was observed in male rats receiving
      o-, m-, or p-nitrotoluene and included hyaline droplet nephropathy and an
      associated increase in the renal concentration of alpha 2U-globulin. Evidence of
      liver toxicity in the male rats receiving o-nitrotoluene included hepatocyte
      vacuolization, oval cell hyperplasia, and increased serum bile acids, sorbitol
      dehydrogenase, and alanine aminotransferase. Although there was no
      histopathologic evidence of hepatic toxicity in male or female rats given the m-
      or p-isomers or in female rats given the o-isomer, treatment-related hepatic
      effects were detected in these groups, as measured by an increase in the relative
      liver weights and by elevations in serum bile acids and liver-specific enzymes.
      The spleens of treated male and female rats had a mild increase in hematopoiesis,
      hemosiderin deposition, and/or congestion. These splenic changes were slightly
      more prominent in rats administered the o- and p-isomers. Administration of o-, m
      , or p-nitrotoluene impaired testicular function in the rat, as shown by
      testicular degeneration and reduction in the density, motility, and number of
      sperm cells. Administration of each isomer to rats caused increases in the length
      of the estrus cycle. The only histopathologic evidence for treatment-related
      toxicity in mice in the 13-week studies occurred in animals receiving the o
      nitrotoluene isomer where the chemical caused degeneration and metaplasia of the
      olfactory epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7519573
TI  - [Hepatocellular carcinoma in pregnancy].
AB  - Primary hepatocellular carcinoma is a very rare disease, especially in
      association with a pregnancy. We report on a 22-year-old primigravida, who
      underwent Caesarean section in the 29th week of pregnancy in conjunction with
      tumour-reductive surgery for hepatocellular carcinoma. The further course of the
      disease was characterised by an early recurrence and lung metastases. Under
      palliative chemotherapy with 5-fluorouracil, the patient has been in a state of
      stable disease for several months. Typical risk factors for the hepatocellular
      carcinoma do not exist in the patient. Alternative explanations for the aetiology
      of the disease are discussed.

PMID- 7519576
TI  - Trophoblast production of hCG and ahCG from normal and abnormal pregnancies.
AB  - This study was designed to correlate early pregnancy outcome with serum and
      trophoblastic culture media levels of hCG, alpha hCG, and the alpha hCG/hCG
      ratio. Maternal serum was obtained from 104 women with normal gestations (n =
      25), ectopic pregnancies (n = 43) and spontaneous abortions (n = 36);
      trophoblastic tissue was obtained from 10 subjects in each group. The alpha
      hCG/hCG ratio was abnormally elevated in the serum of 46% of women with abortions
      and 26% of those with ectopic pregnancies. Tissue culture experiments confirmed
      the relative increase in alpha hCG levels. Deteriorating trophoblast tissue from
      compromised or poorly oxygenated placental implantations results in abnormally
      elevated alpha hCG/hCG ratios; this occurs secondary to a greater relative
      decrease in hCG than alpha hCG production. The clinical utility of this knowledge
      is under investigation.

PMID- 7519575
TI  - Comparison of phylogenetic relationships based on phospholipid fatty acid
      profiles and ribosomal RNA sequence similarities among dissimilatory sulfate
      reducing bacteria.
AB  - Twenty-five isolates of dissimilatory sulfate-reducing bacteria were clustered
      based on similarity analysis of their phospholipid ester-linked fatty acids
      (PLFA). Of these, 22 showed that phylogenetic relationships based on the sequence
      similarity of their 16S rRNA directly paralleled the PLFA relationships.
      Desulfobacter latus and Desulfobacter curvatus grouped with the other
      Desulfobacter spp. by 16S rRNA comparison but not with the PLFA analysis as they
      contained significantly more monoenoic PLFA than the others. Similarly,
      Desulfovibrio africanus clustered with the Desulfovibrio spp. by 16S rRNA but not
      with them when analyzed by PLFA patterns because of higher monoenoic PLFA
      content. Otherwise, clustering obtained with either analysis was essentially
      congruent. The relationships defined by PLFA patterns appeared robust to shifts
      in nutrients and terminal electron acceptors. Additional analyses utilizing the
      lipopolysaccharide-lipid A hydroxy fatty acid patterns appeared not to shift the
      relationships based on PLFA significantly except when completely absent, as in
      Gram-positive bacteria. Phylogenetic relationships between isolates defined by
      16S rRNA sequence divergence represent a selection clearly different from the
      multi-enzyme activities responsible for the PLFA patterns. Determination of
      bacterial relationships based on different selective pressures for various
      cellular components provides more clues to evolutionary history leading to a more
      rational nomenclature.

PMID- 7519577
TI  - [What kind of physical therapy in sympathetic reflex dystrophy?].

PMID- 7519574
TI  - [Viral hepatitis C].

PMID- 7519578
TI  - [Agraphia of Gerstmann syndrome--attempt at characterization].
AB  - A review is given of well documented cases of Gerstmann's syndrome covering one
      century from 1888 to 1991 complemented by two own observations, Convergencies as
      well as divergencies are pointed out. It is concluded, that although aphasia may
      be an accompanying condition, aphasic agraphia as described in linguistic terms
      is not a sufficient explanation of agraphia in Gerstmann's syndrome which implies
      spatial-graphic particularities like disturbances of symmetry, reduplications of
      strokes, defective line orientation, choice of a different letter type and
      occurrence of nonsense characters not contained in the alphabet. Literal
      paragraphs may appear as well, while semantic errors are virtually lacking. These
      features are known to occur in apractic or constructive agraphia whose
      localisation is usually in the left angular/subangular region coincident with a
      disconnection from homotopic right hemisphere areas by damage of commissural
      fibres. Lesions of these non-dominant areas may lead to spatial agraphia.

PMID- 7519579
TI  - [Cerebral sinus-venous thrombosis in protein S deficiency].
AB  - The coagulation inhibitor protein S is a cofactor for the protein C, which
      inactivates the factors V and VIII. In very rare cases a congenital or acquired
      protein S deficiency leads to a cerebral sinus or venous thrombosis. Guided by an
      own case report the other 15 cases of the literature are described. In most cases
      there was a thrombosis of the sinus sagittalis superior. Usually the active form,
      which is not bound to protein in plasma, is reduced. Women are more frequently
      involved than men. Partly there are additional risk factors to inheritance, such
      as pregnancy, puerperium or anticonceptive pills. In the acute stage the patients
      have to be treated with heparin, afterwards for a long time with dicumarol.

PMID- 7519580
TI  - Monoclonal antibody against the active site of caeruloplasmin and the ELISA
      system detecting active caeruloplasmin.
AB  - Serum caeruloplasmin deficiency is a characteristic biochemical abnormality found
      in patients with Wilson's disease, but the mechanism of this disease is unknown.
      Although the phenylenediamine oxidase activity of serum caeruloplasmin is
      markedly low in patients with Wilson's disease, mRNA of caeruloplasmin exists to
      some extent. To investigate the deficiency of caeruloplasmin oxidase activity in
      Wilson's disease, we generated 14 monoclonal antibodies (MAbs) and selected ID1,
      which had the strongest reactivity, and ID2, which had neutralizing ability. We
      also established a system to measure active caeruloplasmin specifically using
      these MAbs. These MAbs and the system will be useful tools in analyzing the
      active site of caeruloplasmin in patients with Wilson's disease.

PMID- 7519581
TI  - Production and characterization of monoclonal antibodies against the ribosome
      inactivating proteins dianthin32 and momochin.
AB  - Female BALB/c mice were immunized with either dianthin32 or momochin, type 1
      ribosome-inactivating proteins (RIPs) derived from Dianthus charyophyllus and
      Momordica cochinchinensis, respectively. Five anti-dianthin32 and 6 anti-momochin
      secreting hybridomas were obtained by somatic fusion of lymphocytes with myeloma
      cell line NS0. The monoclonal antibodies (MAbs) produced were highly specific, as
      demonstrated by cross-reactivity assays performed with taxonomically related and
      unrelated type 1 RIPs, and recognized different epitopes of the antigen. The
      affinity constant of anti-RIPs MAbs ranged between 10(8) M-1 and 10(10) M-1.

PMID- 7519582
TI  - Reliability of pyuria detection method.
AB  - The reliability of two methods for the detection of pyuria was studied in a total
      of 106 urine samples obtained from patients with identifiable underlying urinary
      tract disease. The coefficient of variation (CV) was significantly higher in the
      microscopic than in the counting chamber method. The CV obtained with the use of
      the KOVA slide 10 grid, a disposable and less expensive counting chamber, was
      identical to that obtained with the Burker-Turk counting chamber. Only 50% of the
      patients who were proven to have pyuria of > or = 5 WBCs/HPF by the microscopic
      method had significant bacteriuria of > or = 10(4) bacteria per ml of urine. On
      the other hand, 95% and 90% of the patients who were proven to have pyuria of >
      or = 10 WBCs/mm3 with the Burker-Turk and Fuchs-Rosenthal counting chambers had
      significant bacteriuria. It was concluded that the counting chamber provides a
      reliable method for the detection of pyuria and is highly predictive for the
      presence of significant bacteriuria. The KOVA slide 10 grid is an acceptable
      alternative to the regular counting chamber.

PMID- 7519583
TI  - Hepatitis C and hepatitis B virus infection in hemodialysis patients and staff: a
      two year follow-up.
AB  - To estimate the prevalence of antibodies to the hepatitis C virus ((HCV) and
      hepatitis virus (HBV) and the presence of infection, 101 patients receiving renal
      replacement therapy and 75 staff members caring for them were tested. Evaluation
      included detailed history, screening for anti-HCV antibody, HBV markers and liver
      enzymes 38% of patients were anti-HCV positives and 15 (40%) of these had
      antibodies to the hepatitis B core antigen indicating previous hepatitis B
      infection. Positive markers indicating HBV infection only, accounted for another
      18% of patients. All staff members were anti-HCV negative, although 34 (45%) were
      anti-HBc positive. Age, sex and history of blood transfusions did not influence
      the prevalence of anti-HCV and anti-HBC in patients. There was, however, a
      significant difference in the prevalence of anti-HCV and anti-HBc positivity
      between polytransfused and occasionally transfused patients (p < 0.05). During a
      24-months follow-up a decline was observed in HBs antigen carriers from 20% to
      10% and in HBc antibody carriers from 47% to 33%. At the same time, regardless of
      accurate preventive measures, an increase in incidence of anti-HCV seropositivity
      from 30% to 38% was detected.

PMID- 7519585
TI  - Differential expression of the cell-cell adhesion molecule E-cadherin in ascites
      and solid human ovarian tumor cells.
AB  - Advanced ovarian cancers contain 2 distinct phenotypic populations: (a) free
      floating tumor cells in the ascitic fluid and (b) solid tumors. Ascites cells are
      derived from the solid tumors and spread throughout the peritoneum. Changes in
      cell-cell and cell-extracellular matrix interactions are thought to be
      responsible for the origin of ascites cells. Since E-cadherin molecules play a
      crucial role in the cell-cell interactions in epithelial cells, we investigated
      the expression of E-cadherin in these 2 phenotypic populations. Paired samples of
      ascites and solid tumors were obtained from patients. Both primary tumors and
      tumor cells isolated from an experimental model showed a marked decrease in E
      cadherin expression in the ascites cells compared to the respective solid tumors.
      Semi-quantitative, reverse transcriptase-polymerase chain reaction (RT-PCR) was
      used to determine the steady-state levels of E-cadherin-specific mRNA. Results
      indicate that the primary tumors had significantly lower levels of E-cadherin
      transcript in ascites cells when compared to their solid tumor counterparts.
      Changes in E-cadherin expression were also reflected in the invasion capacity of
      tumor cells in vitro. Ascites cells were 4-fold more invasive then solid tumor
      cells, suggesting that ascites cells are a highly malignant phenotype.

PMID- 7519584
TI  - Fibroblast activation protein: purification, epitope mapping and induction by
      growth factors.
AB  - The human fibroblast activation protein (FAP) defined by monoclonal antibody
      (MAb) F19 is a cell surface antigen expressed in reactive stromal fibroblasts of
      breast, colorectal, lung and other epithelial cancers. In contrast to its stroma
      specific localization in epithelial neoplasms, FAP is expressed in the malignant
      mesenchymal cells of bone and soft tissue sarcomas. FAP is transiently expressed
      in some fetal mesenchymal tissues but is absent or expressed at low levels in
      most adult tissues. FAP is induced in cultured fibroblasts and, in these cells,
      consists of a M(r) 95,000 subunit (FAP alpha) carrying the F19 epitope and a non
      covalently bound M(r) 105,000 subunit (FAP beta) lacking the F19 epitope. Using
      MAb F19 and 5 newly derived MAbs, we identify 3 distinct epitopes on FAP alpha
      and tentatively assign one epitope to FAP beta. Analysis of detergent extracts of
      a FAP alpha high beta- sarcoma cell line by size exclusion-high performance
      liquid chromatography (HPLC) revealed that FAP alpha does not elute as a M(r)
      95,000 species but as part of a high-molecular weight complex (M(r) > 400,000)
      that dissociates into M(r) 95,000 subunits in SDS gels. Immunoaffinity
      purification of FAP alpha followed by tryptic digestion, reversed-phase HPLC and
      microsequencing identified 3 unique FAP alpha peptides, with 2 showing sequence
      similarity (23/38 identical amino acids) to segments of CD26, a T-cell activation
      antigen. CD26 is a membrane-bound enzyme (dipeptidyl aminopeptidase IV), but
      immunopurified FAP alpha has little if any dipeptidase activity with typical CD26
      substrates. Finally, studies with FAPlow leptomeningeal fibroblasts revealed that
      transforming growth factor-beta, 12-O-tetradecanoyl phorbol-13-acetate and
      retinoids can upregulate FAP expression, whereas serum and several other factors
      had no or little effect on FAP levels. FAP and CD26 may belong to a family of
      structurally related but functionally distinct activation proteins that are
      expressed on different cell types and show unique modes of regulation in normal
      and malignant cells.

PMID- 7519586
TI  - Therapy of human T-cell acute lymphoblastic leukaemia in severe combined
      immunodeficient mice with two different anti-CD7-saporin immunotoxins containing
      hindered or non-hindered disulphide cross-linkers.
AB  - A SCID mouse model of human T-ALL has been used to determine the in vivo
      therapeutic efficacy of two anti-CD7-saporin immunotoxins constructed with either
      a hindered (HB2-SMPT-Sap) or non-hindered (HB2-SPDP-Sap) disulphide bond between
      antibody and saporin. Groups of 10 SCID mice were injected intravenously (i.v.)
      with 2 x 10(6) human T-ALL HSB-2 cells followed seven days later by i.v.
      injection with either a single dose or with 3 doses of HB2-SPDP-Sap or HB2-SMPT
      Sap given on alternate days. Control groups received equivalent sham injections
      of PBS or molar equivalent amounts of unconjugated HB2 antibody+saporin. Animals
      receiving a single dose of HB2-SMPT-Sap showed better survival than animals
      receiving a single dose of HB2-SPDP-Sap but the difference was not shown to be
      significant by log-rank analysis. When given as a triple dose both immunotoxins
      performed similarly. Comparison of single-dose with triple-dose IT therapy
      revealed that the therapeutic effect of a triple dose of HB2-SPDP-Sap was
      significantly better than that of single dose, but this was not the case with HB2
      SMPT-Sap. Pharmacokinetic studies of HB2-SPDP-Sap and HB2-SMPT-Sap in normal and
      HSB-2 leukaemia bearing SCID mice failed to reveal any difference in clearance
      rates for these two IT's. We conclude from these studies that there is no
      therapeutic advantage to be gained from constructing the HB2-Sap IT with a
      hindered disulphide bond in this particular model of human T-ALL.

PMID- 7519587
TI  - Different characteristics of hepatoid and non-hepatoid alpha-fetoprotein
      producing gastric carcinomas: an experimental study using xenografted tumors.
AB  - The characteristics, including metastatic potential, of 5 xenografts of alpha
      fetoprotein (AFP)-producing gastric carcinomas in nude mice, designated TSG1,
      TSG3, TSG11, TSG17 and TSG20, were examined. Of these xenografts, TSG1, TSG11 and
      TSG20 were regarded as hepatoid adenocarcinomas based on their morphological
      resemblance to hepatocellular carcinoma, frequent immunoreactivity for liver-cell
      markers, and excessive production of AFP with a high concanavalin A (Con-A)
      binding property of hepatic type. On the other hand, TSG3 and TSG17 tumors showed
      the features of poorly differentiated medullary adenocarcinoma with scattered AFP
      positive cells consistent with low AFP levels in mouse sera, and negative
      immunoreactivity for other liver-cell markers. Ultrastructurally, these tumors
      were composed of undifferentiated cells with a little adenocarcinomatous
      differentiation. Moreover, the AFP produced by TSG3 and TSG17 tumors had an
      extremely high Con-A nonbound fraction (80% to 90%), which was different from
      that of the hepatic or yolk-sac types. Therefore, both TSG3 and TSG17 tumors were
      regarded as non-hepatoid, poorly differentiated adenocarcinomas which could be
      differentiated from any types of AFP-producing gastric carcinoma. Furthermore,
      cells from hepatoid adenocarcinoma strains (TSG1, TSG11 and TSG20) injected into
      the spleens of nude mice produced liver metastases in all the mice examined,
      whereas cells from non-hepatoid carcinoma strains (TSG3 and TSG17) produced few
      or no liver metastases. Our data show that some non-hepatoid AFP-producing
      gastric carcinomas have lower liver-metastasizing potential than hepatoid AFP
      producing gastric carcinomas.

PMID- 7519588
TI  - Hypermethylation of replicating hepatic DNA following N-methyl-N-nitrosourea
      administration.
AB  - Changes in the degree of methylation of cytosine in DNA are considered to be
      mechanistically important in modulating gene expression. To gain a better
      understanding of the relationship(s) linking onco-proliferative processes and
      enzymatic DNA methylation, a study has been carried out on the hepatic DNA
      methylation pattern during DNA replication following partial hepatectomy (PH),
      mitogen treatment and N-methyl-N-nitrosourea (MNU) administration in rats. The
      following results were obtained: (i) DNA hypomethylation was seen during DNA
      synthesis, with each of the 3 stimuli, namely MNU administration, partial
      hepatectomy, and hepatomitogen treatment; (ii) the level of DNA hypomethylation
      was not quantificatively related to the extent of DNA replication as measured by
      incorporation of [3H]thymidine into hepatic DNA; (iii) MNU administration under
      conditions conducive to carcinogenic development, i.e. during the S phase of
      compensatory cell proliferation, caused hypermethylation of replicating hepatic
      DNA, as shown by HpaII and MspI restriction patterns.

PMID- 7519589
TI  - A comparative study of radioligand (DCC) and modified immunoperoxidase anti
      estrogen receptor techniques in breast carcinoma.
AB  - This study deals with the pattern of estrogen receptors in 52 cases of invasive
      breast carcinoma by comparing the ligand-binding assays with dextran-coated
      charcoal (DCC) to an immunoperoxidase assay (IPE) technique in paraffin-embedded
      material from the same tumor. A modification of the IPE by adding cobalt chloride
      in the final reaction and counter-staining with eosin instead of hematoxylin was
      introduced. A significantly high correlation was found between the two compared
      methods (80.8% positivity by the DCC method and 80% by the IPE method). The
      correlation was very significant in cases where the immunohistochemical grading
      was higher than 4 (according to our semi-quantitative evaluation scale of 0-8),
      and for these cases we suggest the IPE method as highly specific and precise.

PMID- 7519590
TI  - [Value of the patient's own test substances in epicutaneous testing].
AB  - Patch testing with commercially available test kits of known allergens often
      leads to detection of the responsible allergen. In many cases, however, the
      responsible allergen cannot be found unless the patient's "own" products or
      chemicals are tested. An analysis of 2460 patch tests with patch test kits
      proposed by the DKG (German Contact Allergy Group) and a positive history of a
      patient's own substance showed positive results in 208 patients with 289
      products. In 44% (129 out of 289) the responsible allergen could only be found by
      testing the patient's own substances, in 56% (160 out of 289) the same allergen
      as was responsible for the positive result with patients' endogenous substances
      was positive in one of the commercially available test kits. The substances that
      tested positive were medical products/adhesives (45%), cosmetics (39.4%), rubber
      materials (4.1%), leather materials (0.7%) and others (10%). Subsequent testing
      of the different components of the patients' own substances that tested positive
      was carried out in 45 cases and resulted in the detection of new allergens, such
      as tris-(2-hydroxyethyl)isocyanurate triacrylate. In 27 patients the endogenous
      substances had tested positive in the course of testing for occupational
      dermatitis, and in 10 of these positive testing of a patient's own product
      resulted in notification of an occupational dermatitis. These results show, that
      patch testing with the patients own products if very important for the finding of
      the responsible or even new allergens.

PMID- 7519591
TI  - [The Merkel cell].

PMID- 7519592
TI  - [Palliative antineoplastic chemotherapy of patients with head and neck tumors].
AB  - Palliative chemotherapy in patients with head and neck cancer after failing
      previous treatment is generally accepted clinically although real benefits for
      patients remain controversial. Proponents may feel morally obliged to offer
      patients this remaining opportunity for further care. Additionally, palliative
      therapy may have certain favorable effects for the patient, such as pain relief
      and facilitating swallowing. Critics note that there is no prolongation of
      survival time and patients may experience a decreased quality of life because of
      side effects due to treatment. In these cases antineoplastic drugs cannot be
      targeted to the tumor region because patients develop a poor tissue vascularity
      in areas previously radiated or operated upon. Our department has treated 34
      patients with advanced cancers, using single drug therapy with carboplatin in 19
      patients and methotrexate in 6 patients and combination chemotherapy with
      cisplatin and methotrexate in 9 patients. The average survival time following
      palliative chemotherapy was 6.5 months. When patients experienced serious side
      effects and decreased quality of life, therapy was discontinued. However, two
      patients with inoperable tumors of the epipharynx undergoing this form of
      treatment survived for 18 and 24 months respectively, with an improved quality of
      life, as detailed in this report. The best palliative results were achieved in
      patients with tumors of the nasopharynx, nose and paranasal sinuses when compared
      to other head and neck localizations. These results were independent of the T
      stage but were especially notable in patients without tumor involvement in neck
      lymph nodes or N1 tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519594
TI  - Molecular characterization of three loss-of-function mutations in the
      isopenicillin N-acyltransferase gene (penDE) of Penicillium chrysogenum.
AB  - Five mutants of Penicillium chrysogenum blocked in penicillin biosynthesis (npe)
      which are deficient in isopenicillin N-acyltransferase were isolated previously.
      Three of these mutants, npe6, npe7, and npe8, have been characterized at the
      molecular level and compared with npe10, a deletion mutant. Transcripts of normal
      size (1.15 kb) of the penDE genes, which encode isopenicillin N-acyltransferase,
      and also of the pcbAB (11.5 kb) and pcbC (1.1 kb) genes were observed in all
      mutants except for the npe10 mutant. Immunoblotting studies using antibodies
      against isopenicillin N-acyltransferase showed that all mutants (except npe10)
      formed the 40-kDa (unprocessed) protein and the 29-kDa subunit of the
      isopenicillin N-acyltransferase. The 11-kDa subunit could not be observed in the
      immunoblots. The mutant penDE genes of strains npe6, npe7, and npe8 were cloned
      and sequenced. These three strains showed a mutation in the penDE genes which
      results in a single amino acid change in each modified isopenicillin N
      acyltransferase. The mutation in npe6 resulted in a change of Gly-150 to Val,
      whereas the mutation in both npe7 and npe8 introduced a change of Glu-258 to Lys.
      Replacement of the Val-150 and Lys-258 mutations by constructing hybrid
      isopenicillin N-acyltransferase molecules led to the recovery of the
      isopenicillin N-acyltransferase activity. The mutations in npe6, npe7, and npe8
      do not affect the ability of the 40-kDa isopenicillin N-acyltransferase to be
      processed into the component subunits.

PMID- 7519593
TI  - apbA, a new genetic locus involved in thiamine biosynthesis in Salmonella
      typhimurium.
AB  - In Salmonella typhimurium, the synthesis of the pyrimidine moiety of thiamine can
      occur by utilization of the first five steps in de novo purine biosynthesis or
      independently of the pur genes through the alternative pyrimidine biosynthetic,
      or APB, pathway (D. M. Downs, J. Bacteriol. 174:1515-1521, 1992). We have
      isolated the first mutations defective in the APB pathway. These mutations define
      the apbA locus and map at 10.5 min on the S. typhimurium chromosome. We have
      cloned and sequenced the apbA gene and found it to encode a 32-kDa polypeptide
      whose sequence predicts an NAD/flavin adenine dinucleotide-binding pocket in the
      protein. The phenotypes of apbA mutants suggest that, under some conditions, the
      APB pathway is the sole source of the pyrimidine moiety of thiamine in wild-type
      S. typhimurium, and furthermore, the pur genetic background of the strain
      influences whether this pathway can function under aerobic and/or anaerobic
      growth conditions.

PMID- 7519597
TI  - The abundance of atp gene transcript and of the membrane F1F0-ATPase as a
      function of the growth pH of alkaliphilic Bacillus firmus OF4.
AB  - Molecular biological and biochemical studies of the F(1)F(0)-ATP synthase of
      alkaliphilic Bacillus firmus OF4 show that the enzyme used at pH 7.5 and pH 10.5
      is a unique product of the atp operon, expressed at the same levels and yielding
      an enzyme with the same subunit properties and c-subunit/holoenzyme
      stoichiometry.

PMID- 7519598
TI  - Sialyl Lewis X mimics derived from a pharmacophore search are selectin inhibitors
      with anti-inflammatory activity.
AB  - The selectins, a family of adhesion receptors involved in leukocyte
      extravasation, recognize sialyl Lewis X (sLe(x); NeuAc alpha 2-3Gal beta 1-4(Fuc
      alpha 1-3)GlcNAc) and related oligosaccharides. We used conformational energy
      computations, high field NMR, and structure-function studies to define distance
      parameters of critical functional groups of sLe(x). This sLe(x) pharmacophore was
      used to search a three-dimensional data base of chemical structures. Compounds
      that had a similar spatial relationship of functional groups were tested as
      inhibitors of selectin binding. Glycyrrhizin, a triterpene glycoside, was
      identified and found to block selectin binding to sLe(x) in vitro. We substituted
      different sugars for the glucuronic acids of glycyrrhizin and found the L-fucose
      derivative to be the most active in vitro and in vivo. A C-fucoside derivative,
      synthesized on a linker designed for stability and to more closely approximate
      the original sLe(x) pharmacophore, resulted in an easily synthesized, effective
      selectin blocker with anti-inflammatory activity.

PMID- 7519595
TI  - micF antisense RNA has a major role in osmoregulation of OmpF in Escherichia
      coli.
AB  - micF RNA, produced from a multicopy plasmid, was originally shown to be a major
      factor in negative osmoregulation of the OmpF outer membrane protein in
      Escherichia coli. However, subsequent experiments with a micF deletion strain
      suggested that chromosomal micF RNA was not a key component in this process. We
      report here that micF RNA is essential for the reduction in OmpF levels in cells
      grown in media of low-to-intermediate levels of osmolarity. Under these
      conditions, the amount of OmpF was reduced up to 60% in the parent strain while
      OmpF levels were not altered in the micF deletion mutant. In medium of higher
      osmolarity, OmpF synthesis was strongly inhibited in both strains. RNA
      measurements showed that micF RNA levels rose rapidly in cells grown in low-to
      intermediate levels of osmolarity concomitant with the reduction in OmpF protein,
      while ompF mRNA decreased strongly only during high-osmolarity conditions. Taken
      together, these results strongly suggest that the negative osmoregulation of OmpF
      at low-to-intermediate osmolarity levels requires micF RNA and that this is
      masked at higher osmolarity by the known strong inhibition of OmpF transcription
      by OmpR. Results consistent with this model were also obtained by using procaine,
      a compound reported to inhibit ompF expression by a mechanism very similar to
      that involved in osmoregulation.

PMID- 7519596
TI  - Structure, expression, and regulation of the kilC operon of promiscuous IncP
      alpha plasmids.
AB  - The kil-kor regulon was first identified on the broad-host-range IncP alpha
      plasmid RK2 by the presence of multiple kil loci (kilA, kilB, kilC, and recently
      kilE) that are lethal to Escherichia coli host cells in the absence of regulation
      by kor functions in various combinations. Whereas the kilB operon is required for
      mating-pair formation during conjugation, the functions encoded by the other kil
      loci are not known. They are not essential for replication or conjugal transfer,
      but their coregulation with replication and transfer genes indicates that they
      are likely to be important for RK2. In this report, we describe molecular and
      genetic studies on kilC. We determined the nucleotide sequence of the kilC
      region, which is located between the origin of vegetative replication (oriV) and
      transposon Tn1 on RK2. Primer extension analysis identified the transcriptional
      start site and showed that a sequence corresponding to a strong sigma 70 promoter
      is functional. The abundance of RNA initiated from the kilC promoter is reduced
      in the presence of korA and korC, as predicted from genetic analysis of kilC
      regulation. The first gene of the kilC operon (klcA) is sufficient to express the
      host-lethal phenotype of the kilC determinant in the absence of korA and korC. By
      comparing RK2 to the related IncP alpha plasmids pUZ8 and R995, we determined
      that the Tn1 transposon in RK2 interrupts a gene (klcB) immediately downstream of
      klcA. Thus, the kilC determinant is normally part of an autoregulated operon of
      three genes: klcA, klcB, and korC. klcA is predicted to encode a 15,856-Da
      polypeptide that is related to the ArdB antirestriction protein of the IncN
      plasmid pKM101, suggesting a role for klcA in the broad host ranges of IncP alpha
      plasmids. The predicted product of the uninterrupted klcB gene is a polypeptide
      of 51,133 Da that contains a segment with significant similarity to the RK2
      regulatory proteins KorA and TrbA. Located 145 bp upstream of the kilC promoter
      is a 10th copy of the 17-bp oriV iteron sequence in inverted orientation relative
      to that of the other nine iterons of oriV. Iteron 10 is identical to the "orphan"
      iteron 1, and both have identical 6-bp flanking sequences that make them likely
      to be strong binding sites for the TrfA replication initiator protein. The
      locations and relative orientation of orphan iterons 10 and 1 raise the
      possibility that these iterons promote the formation of a DNA loop via protein
      protein interactions by bound TrfA and lead us to propose that they demarcate the
      functional origin of replication. This analysis of the kilC region and our
      previous studies on the other kil loci of RK2 have revealed that the region
      between oriV and the korABF operon in wild-type IncP alpha plasmids is saturated
      by the kilC, kilE, and kilA loci arranged in four kor-regulated operons encoding
      a total of 12 genes.

PMID- 7519599
TI  - Liver expression of epidermal growth factor RNA. Rapid increases in immediate
      early phase of liver regeneration.
AB  - The liver exhibits a remarkable capacity to regenerate its mass following partial
      removal or after injury. Transmembrane receptors for epidermal growth factor
      (EGF) are highly expressed in liver cells, which quickly respond to this
      polypeptide mitogen by activating an intrinsically low rate of cell division.
      Although EGF appears to regulate liver growth, its significance has remained
      unclear, and only a small change in serum levels can be detected during
      hepatocellular proliferation. Using a reverse transcription-polymerase chain
      reaction assay, we report here the novel finding that EGF RNA transcripts are
      synthesized in a hepatic cell-specific pattern, appearing in hepatocyte and
      lipocyte cell types. Our data reveal that within 15 min following a 70% liver
      removal, EGF RNA levels increase > 10-fold and then diminish below basal levels
      prior to the first wave of regenerative cell division. Immunoanalysis of
      metabolically labeled hepatocytes shows that EGF accumulates as a large 60-kDa
      peptide. These results demonstrate that EGF transcription is a previously
      unrecognized component of hepatic gene expression, and rapid increases in EGF RNA
      levels in the immediate-early phase of liver regeneration point to EGF as an
      autocrine factor in the prereplicative hepatic growth program.

PMID- 7519600
TI  - Vitronectin gene expression in vivo. Evidence for extrahepatic synthesis and
      acute phase regulation.
AB  - A competitive polymerase chain reaction (PCR) assay was developed to quantitate
      vitronectin (Vn) mRNA in murine tissues using a synthetic RNA as an external
      standard. Although the liver contained the highest concentration of Vn mRNA,
      significant levels were also detected in the brain (25-fold less) and in adipose
      tissue, heart, and skeletal muscle (100-fold less than liver). Lower
      concentrations also were detected in the lung, uterus, testis, and thymus, and
      little or no Vn mRNA could be detected in kidney, spleen, and blood. These
      results indicate that significant amounts of Vn mRNA are produced in extrahepatic
      organs. The regulation of Vn gene expression in vivo was studied in a murine
      model system in which acute systemic inflammation was induced by endotoxin
      administration. Plasma Vn levels increased 2- to 3-fold within 16 h after
      endotoxin administration and remained elevated for up to 72 h. This increase
      appeared to result from increased synthesis in the liver since the steady-state
      level of hepatic Vn mRNA increased 4-fold after endotoxin administration.
      Moreover, Vn mRNA levels in heart, lung, and brain were not significantly
      increased by endotoxin. These results suggest that Vn gene expression in vivo is
      regulated in a tissue-specific manner and identify Vn as a novel acute phase
      reactant.

PMID- 7519601
TI  - GLEPP1, a renal glomerular epithelial cell (podocyte) membrane protein-tyrosine
      phosphatase. Identification, molecular cloning, and characterization in rabbit.
AB  - Podocytes are specialized epithelial cells with delicate interdigitating foot
      processes which cover the exterior basement membrane surface of the glomerular
      capillary. They are in part responsible for the extraordinary charge and size
      filtration characteristics of the glomerulus. To better understand disease
      processes affecting the glomerular filter, we searched for proteins with relative
      specificity to the podocyte using a monoclonal antibody strategy. The first such
      protein characterized (designated glomerular epithelial protein 1 (GLEPP1)) is a
      membrane protein-tyrosine phosphatase (PTPase) with a large extracellular domain
      containing eight fibronectin type III-like repeats, a hydrophobic transmembrane
      segment, and a single PTPase domain. The GLEPP1 PTPase domain shows homology with
      two other single domain transmembrane PTPases (PTP beta and Drosophila central
      nervous system PTP10D). This homology includes 2 cysteines in the PTPase domain
      not present in intracellular or tandem domain membrane PTPases. GLEPP1 PTPase
      protein is distributed to the podocyte foot processes themselves. RNase
      protection assay shows that GLEPP1 mRNA is also present in brain. By analogy with
      the CD45 PTPase of T cells, we expect that this receptor might play a role in
      maintaining foot process structure and/or function by regulating tyrosine
      phosphorylation of podocyte proteins.

PMID- 7519602
TI  - Molecular characterization of the melanocyte lineage-specific antigen gp100.
AB  - The glycoproteins recognized by monoclonal antibody (mAb) NKI-beteb are among the
      best diagnostic markers for human melanoma because their expression is restricted
      to melanocytic cells. Recently, we isolated a cDNA clone, termed gp100-c1, which
      confers immunoreactivity not only to mAb NKI-beteb, but also to two other mAbs
      used to diagnose malignant melanoma, HMB-50 and HMB-45. In this report, we
      demonstrate that gp100-c1 cDNA encodes glycoproteins of 100 kDa (gp100) and 10
      kDa (gp10) which are recognized by these mAbs in human melanoma cells. The
      translation product deduced from the open reading frame present in gp100-c1 cDNA
      is highly homologous to another melanocyte-specific protein, Pmel17. Nucleotide
      sequence analysis of genomic DNA indicates that the transcripts corresponding to
      gp100 and Pmel17 cDNAs originate from a single gene via alternative splicing. In
      all normal and malignant melanocytic cells analyzed, gp100 and Pmel17 RNAs are
      simultaneously expressed.

PMID- 7519603
TI  - Complexes between serpins and inactive proteinases are not thermodynamically
      stable but are recognized by serpin receptors.
AB  - The serpin mechanism of action may resemble the "standard mechanism" described
      for small protein inhibitors of serine proteinases. Since these inhibitors are
      able to bind active site-modified target proteinases, we have investigated the
      interactions between two serpins and their 3,4-dichloroisocoumarin (DCI)
      inactivated target proteinases. alpha 2-Antiplasmin and alpha 1-proteinase
      inhibitor bound stoichiometrically to DCI-inactivated chymotrypsin (EC 3.4.21.1)
      and DCI-inactivated human neutrophil elastase, respectively. Similar to active
      proteinases, the DCI-inactivated proteinases failed to bind complexes between
      serpins and synthetic reactive site loop peptides. Thus, the abilities of active
      and inactive proteinases to bind the serpins probably depend on the same
      structural characteristics. The thermodynamic stability of the alpha 2
      antiplasmin-DCI/chymotrypsin and alpha 1-proteinase inhibitor-DCI/human
      neutrophil elastase complexes was similar to that of virgin serpins. However, in
      mouse plasma elimination studies the two complexes were removed rapidly from the
      circulation, suggesting that they have adopted the receptor recognized
      conformation. Consequently, cleavage of the reactive center peptide bond and
      formation of an inhibitor-acyl enzyme complex is neither obligatory to serpin
      proteinase complex formation nor essential for the conformational change
      responsible for receptor mediated endocytosis.

PMID- 7519604
TI  - Comparative study of three protein-tyrosine phosphatases. Chicken protein
      tyrosine phosphatase lambda dephosphorylates c-Src tyrosine 527.
AB  - To examine the substrate preference of protein tyrosine phosphatases (PTPs), we
      compared the activity of three transmembrane PTPs on dephosphorylation and
      regulation of c-Src and v-Src: chicken PTP lambda (ChPTP lambda), chicken PTP
      alpha (ChPTP alpha), and human leukocyte common antigen-related molecule (HLAR).
      In vitro, all three PTPs dephosphorylated v-Src, but only ChPTP lambda
      dephosphorylated c-Src. Their activities were also compared in Cos cells
      coexpressing Src and the phosphatase domains of three PTPs. These domains were
      fused with peptides for myristylation, so they associated with the cellular
      membrane. When c-Src was coexpressed with myrPTP lambda, its kinase activity was
      elevated 3-4-folds. This activation was less obvious when c-Src was coexpressed
      with myrPTP alpha or myrLAR. Analysis by cyanogen bromide cleavage showed that
      ChPTP lambda and myrPTP lambda dephosphorylated Tyr-527 of c-Src. Our data
      demonstrated the different activities of three PTPs on phosphoproteins,
      suggesting that Src Tyr-527 may require more specific PTP(s) than Src Tyr-416 for
      dephosphorylation in vivo.

PMID- 7519605
TI  - Association of fibroblast growth factor receptor-1 with c-Src correlates with
      association between c-Src and cortactin.
AB  - The initiation of maximal DNA synthesis by fibroblast growth factor (FGF)-1
      requires the presence of the growth factor during the entire G0 to G1 transition
      period of the cell cycle (Zhan, X., Hu, X., Friesel, R., and Maciag, T. (1993) J.
      Biol. Chem. 268, 9611-9620). During this time, the phosphorylation of several
      novel proteins on tyrosine residues occurs, and one of these phosphotyrosyl
      containing proteins has been characterized as the murine homolog of the chicken
      cortactin gene (Zhan, X., Hu, X., Hampton, B., Burgess, W.H., Friesel, R., and
      Maciag, T. (1993) J. Biol. Chem. 268, 24427-24431), a putative substrate for v
      Src. We have examined the possibility that FGF-1 employs c-Src or Src-like
      kinases as signaling intermediates during the mid and late G1 phase of the NIH
      3T3 cell cycle using immunoprecipitation and immunoblot analysis. We have
      demonstrated that c-Src can associate with cortactin in a FGF-1-dependent manner.
      We have also demonstrated that a monoclonal antibody prepared against FGF
      receptor (R)-1 is able to co-precipitate Src-related proteins in lysates from FGF
      1-treated NIH 3T3 cells. Furthermore, a kinase-active form of FGFR-1 expressed in
      a bacterial system was also able to associate with Src kinases in a manner
      dependent on the phosphorylation status of the FGFR-1 protein. Lastly, the Src
      homology (SH)-2 domain of v-Src was able to recognize a recombinant form of FGFR
      1. Because (i) the association between FGFR-1 and Src-like kinases exhibits
      kinetics similar to those observed between the Src kinases and cortactin and (ii)
      the Src-SH2 domain is likely to be involved in the association with FGFR-1, we
      propose that the association of c-Src with activated FGF receptors may be
      responsible for the tyrosine phosphorylation of cortactin during the mid to late
      G1 phase of the cell cycle.

PMID- 7519606
TI  - Localization, synthesis, and processing of surfactant protein SP-C in rat lung
      analyzed by epitope-specific antipeptide antibodies.
AB  - Surfactant protein C (SP-C), a 3.7-kDa hydrophobic lung-specific protein, is
      synthesized and secreted by pulmonary type II cells through proteolytic
      processing of a 21-kDa propeptide (SP-C21) by currently undefined pathways.
      Previously, we reported the production of a polyclonal antibody against rat SP
      C21 (anti-CPROSP-C) using a synthetic peptide as the immunizing antigen (Beers,
      M. F., Wali, A., Eckenhoff, M. E. F., Feinstein, S., Fisher, J. H., and Fisher,
      A. B. (1992) Am. J. Respir. Cell. Mol. Biol. 7, 368-378). In this study, two
      additional epitope-specific proSP-C antibodies produced using synthetic peptide
      sequences were utilized to examine synthetic processing of SP-C. Anti-NPROSP-C
      (Met10-Gln23) and anti-CTERMSP-C (Ser149-Ser166) recognized native proSP-C21
      produced from in vitro translation of SP-C cDNA. Immunocytochemistry using anti
      NPROSP-C confirmed the localization of proSP-C peptides exclusively in type II
      cells. Western analysis of subcellular fractions identified a single 21-kDa band
      in microsomes and a 16-kDa form in lamellar bodies each recognized by all three
      antisera, while anti-NPROSP-C also uniquely identified a prominent 5-6-kDa form
      in lamellar bodies. In a perfused rat lung model labeled with
      [35S]cysteine/methionine, immunoprecipitation of lung homogenate and lamellar
      body fractions identified early appearances of 35S-labeled 21-, 18-, and 16-kDa
      SP-C forms in homogenate and a 16-kDa intermediate form in lamellar bodies. Anti
      NPROSP-C also exclusively detected time-dependent appearances of 5-10-kDa proSP-C
      forms in lamellar bodies and homogenates. Processing of proSP-C21 was completely
      blocked by inclusion of brefeldin A (15 micrograms/ml) in the perfusate. These
      results demonstrate that synthetic peptides can be used to produce epitope
      specific antisera which recognize more hydrophilic domains of proSP-C and show
      that proSP-C processing occurs intracellularly in subcellular compartments of
      type II cells which are distal to the trans-Golgi network.

PMID- 7519607
TI  - L-arginine and calmodulin regulation of the heme iron reactivity in neuronal
      nitric oxide synthase.
AB  - Neuronal nitric oxide synthase (NOS) is a calmodulin-dependent, flavin-containing
      hemoprotein that forms NO from L-arginine, NADPH, and molecular oxygen.
      Calmodulin binding to NOS triggers reduction of its heme groups (Abu-Soud, H.,
      and Stuehr, D.J. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10769-10762), leading
      to NADPH oxidation and NO synthesis. We have examined how L-arginine and
      calmodulin control the ligand binding and electron acceptor properties of the NOS
      heme iron. In the absence of bound calmodulin, ferric NOS exhibited a Kd of 0.6
      microM for L-arginine, as determined by the substrate-dependent shift in heme
      spin equilibrium toward a high spin state. L-Arginine binding reduced the
      affinity of the ferric NOS heme for cyanide by 8-fold. Carbon monoxide binding to
      substrate-free ferrous NOS occurred at a rate of 2 x 10(5) M-1 S-1; this rate was
      decreased 12-fold when L-arginine was bound. In contrast, bound calmodulin did
      not significantly affect cyanide or carbon monoxide binding to the NOS heme, nor
      did it alter NOS binding affinity for L-arginine. Anaerobic titration of a
      calmodulin-bound, L-arginine-free NOS with NADPH led to incomplete reduction of
      the heme iron; full reduction was achieved only in the presence of added L
      arginine. Thus, our data suggest that L-arginine controls NOS heme iron
      reactivity in at least two ways: 1) it slows ligand interactions by binding in
      the distal pocket very near the heme and 2) it also appears to increase the
      reduction potential of the iron. In contrast, bound calmodulin does not alter the
      NOS affinity for L-arginine or heme ligands and may function solely as a switch
      that enables electrons to pass from the flavin domain onto the heme iron.

PMID- 7519608
TI  - Heparin, heparan sulfate, and dermatan sulfate regulate formation of the insulin
      like growth factor-I and insulin-like growth factor-binding protein complexes.
AB  - The mechanisms by which insulin-like growth factor-I (IGF-I) is released from
      insulin-like growth factor binding proteins (IGFBPs) and then binds to its
      receptor have not been defined. This study was designed to determine the role of
      glycosaminoglycans in altering the formation of the IGF-I.IGFBP complexes.
      Heparin inhibited formation of the IGF-I.IGFBP-5 complex and also separated
      preformed IGF-I.IGFBP-5 complexes. Heparin also inhibited formation of the IGF
      I.IGFBP-3 complex; however, it did not inhibit formation of complexes between IGF
      I and IGFBP-1, -2, or -4. Heparin exposure was associated with a 17-fold decrease
      in the affinity of IGFBP-5 for IGF-I. A synthetic peptide that contains residues
      from Arg221 to Arg238 of IGFBP-5, and a heparin binding domain prevented the
      inhibitory effects of heparin on formation of the IGF-I.IGFBP-5 complex. It did
      not directly compete with IGF-I for binding to IGFBP-5, suggesting that heparin
      binding to this region of IGFBP-5 resulted in a conformational change in IGFBP-5
      which lowered its affinity for IGF-I. Other glycosaminoglycans that contained O
      linked sulfates in the 2 or 3 carbon positions of iduronic acid, e.g. heparan
      sulfate and dermatan sulfate, also inhibited the IGF-I.IGFBP-5 complex formation,
      whereas those that did not, such as keratan sulfate or hyaluronic acid, had
      minimal effects. Anionic polysaccharides that contained O-sulfate groups in the 2
      or 3 positions, such as dextran sulfate, pentosan polysulfate, and fucoidan, also
      had inhibitory activity. The findings suggest a role for these compounds in
      inhibiting IGF-I.IGFBP interactions, thus making IGF-I available to bind to its
      receptor.

PMID- 7519609
TI  - Analysis of the control of expression and tissue specificity of the keratin 5
      gene, characteristic of basal keratinocytes. Fundamental role of an AP-1 element.
AB  - The keratin 5 gene presents a complex regulation, since it is expressed at
      different rates in the basal cells of most, if not all, stratified epithelia. We
      have analyzed the 5'-upstream region of the bovine keratin 5 (BK5) gene and found
      that the 5.2 kilobases preceding the gene mimic in vitro the cell type-specific
      expression of BK5. Most of the transcriptional activity maps to an enhancer
      located between positions -762 and -1009. The only regulatory element found in
      this enhancer by electrophoretic mobility shift, competition, and footprinting
      experiments is a consensus AP-1 site. Mutation of this site abolishes the
      activity of the enhancer and reduces to 25% the activity of the 5.2-kilobase
      upstream promoter region. Surprisingly, although the AP-1 presents
      indistinguishable footprints in all cell types tested, the enhancer is active
      only in some of them. Even an oligonucleotide containing the AP-1 region
      protected from DNase I is active in epithelial cells lines but not in NIH 3T3
      fibroblasts, suggesting that this region could constitute an epithelium-specific
      AP-1 element. We also show that BK5 does not respond to phorbol ester induction,
      which suggests that the regulation of this gene by AP-1 must be complex and
      probably different from several other suprabasal, AP-1-regulated cellular and
      viral genes.

PMID- 7519610
TI  - Systematic site-directed mutagenesis of protein SRP19. Identification of the
      residues essential for binding to signal recognition particle RNA.
AB  - Protein SRP19 is an important structural and functional constituent of the signal
      recognition particle (SRP) and belongs to a group of RNA binding proteins that
      specifically recognize certain tetranucleotide loops. Systematic site-directed
      mutagenesis was used to identify the amino acid residues in human SRP19 essential
      for interaction with SRP RNA. In our studies, three different groups of mutants
      were constructed, and each group covered essentially the entire sequence of the
      SRP19 protein in a consecutive nonoverlapping fashion. Results from 10 deletion
      mutants followed by the analysis of 24 mutants in which adjacent five residues
      were changed to pentaglycine suggested that a large portion of the protein may be
      required for RNA binding. Further examination of 53 mutant polypeptides in which
      adjacent dipeptide segments were altered showed, however, that 84 of the 144
      SRP19 amino acids (58%) were not important for binding to the SRP RNA. The
      essential amino acids cluster in five regions which encompass most of the SRP19
      sequence, with the exception of residues located at the N and C termini and a
      predicted internal loop. The results from the systematic site-directed
      mutagenesis study, when combined with protein secondary structure calculations,
      demonstrate that SRP19 is a precisely tooled protein which associates intimately
      with the SRP RNA.

PMID- 7519611
TI  - The cystic fibrosis transmembrane conductance regulator is a dual ATP and
      chloride channel.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to a
      superfamily of proteins implicated in the transport of ions, proteins, and
      hydrophobic substances. Recent studies have demonstrated that CFTR is a protein
      kinase A-sensitive anion channel regulated by ATP. In the present study, patch
      clamp techniques were used to assess the role of CFTR in the transport of Cl- and
      ATP. The stable transfection of mouse mammary carcinoma cells, C127i, with the
      cDNA for human CFTR resulted in the appearance of a diphenylamine-2-carboxylate
      inhibitable Cl- channel, which was activated by cAMP under whole-cell and cell
      attached conditions and by protein kinase A plus ATP under excised, inside-out
      conditions. CFTR expression was also associated with the electrodiffusional
      movement of ATP as indicated by the cAMP activation of ATP currents measured
      under whole-cell conditions. In excised, inside-out patches, it was demonstrated
      that ATP currents were mediated by ATP-conductive channels, which were also
      activated by protein kinase A and blocked by the Cl- channel blocker
      diphenylamine-2-carboxylate under excised, inside-out conditions. Single-channel
      currents observed in the presence of asymmetrical Cl-/ATP concentrations
      indicated that the same conductive pathway was responsible for both ATP and Cl-
      movement. Thus, CFTR is a multifunctional protein with more than one anion
      transport capability and may modify signal transduction pathways for Cl- or other
      secretory processes by the selective delivery of nucleotides to the extracellular
      domain.

PMID- 7519612
TI  - Yeast lariat debranching enzyme. Substrate and sequence specificity.
AB  - Yeast RNA lariat debranching enzyme has been purified to near homogeneity using a
      bacterial overproducer of the enzyme. The enzyme is capable of digesting a
      variety of branched nucleic acid substrates, including group II intron lariats,
      multicopy single-stranded DNAs (msDNAs), and a variety of synthetic branched
      RNAs. A trinucleotide release assay using radiolabeled msDNA substrates was
      developed and used to determine the basic biochemical parameters for the enzyme.
      The debranching enzyme shows a strong preference for purines at the 2'-position
      in both msDNA and synthetic branched RNA substrates, in accord with the structure
      of its native substrate, which always has a 2'-G residue. The use of small
      synthetic branched RNA substrates will allow systematic mechanistic and
      structural studies of this unique enzyme.

PMID- 7519613
TI  - Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of
      activated T-cells: NF45 and NF90.
AB  - Nuclear Factor of Activated T-cells (NF-AT) is a crucial transcription factor
      required for T-cell expression of interleukin 2. Purified NF-AT contains 45-kDa
      and 90-kDa subunits (Corthesy, B., and Kao, P. N. (1994) J. Biol. Chem. 269,
      20682-20690). Partial internal amino acid sequences derived from each subunit
      indicate that these proteins are novel. The amino acid sequences were used to
      clone the cDNAs encoding each subunit. The cDNAs predict proteins of novel
      structures: NF45 has limited similarity to prokaryotic transcription factor sigma
      54 and to human DNA topoisomerase II; NF90 has limited similarity to Drosophila
      Staufen in a domain predicted to bind double-stranded RNA. RNA encoding NF45 and
      NF90 exists in nonstimulated Jurkat T-cells and in all other cell types examined
      (HeLa, HepG2, K562). Immunofluorescence microscopy was used to demonstrate that
      both proteins are located in the nucleus of Jurkat T-cells. Clones NF45 and NF90
      with a polyhistidine fusion tag were transiently expressed and processed in the
      native environment of Jurkat T-cells. Histidine-tagged NF45 and NF90 proteins,
      affinity-purified on nickel chelate columns, encode a NF-AT DNA-binding activity
      that is enhanced following T-cell stimulation, and this enhancement is blocked
      when T-cells are stimulated in the presence of cyclosporin A or FK506.

PMID- 7519615
TI  - Identification of a regulatory domain of the interleukin-6 receptor.
AB  - IL-6 signal transduction occurs when the liganded interleukin-6 receptor (IL-6R)
      interacts with glycoprotein (gp) 130. We hypothesized that synthetic peptides
      modeled from the extramembranous domain of the IL-6R may interfere with the IL-6
      induced reaction between IL-6R and gp130 and may serve to elucidate the initial
      steps in IL-6 signal transduction. The capacity of such peptides to modulate two
      different IL-6 functions was evaluated: 1) IL-6-dependent B9 cell mitogenesis,
      and 2) IL-6-induced acute phase protein synthesis in HepG2 cells. A synthetic
      peptide, 249Y16T264, corresponding to residues 249-264, inhibited IL-6-dependent
      B9 proliferation and IL-6-induced acute phase protein up-regulation in HepG2
      cells. Other peptides modeled from different regions of the IL-6R were not
      inhibitory. 249Y16T264 did not inhibit IL-6-independent HepG2 cell proliferation
      or total cellular protein synthesis. The inhibitory effect was reversible,
      indicating that the peptide was not cytotoxic. 249Y16T264 did not inhibit 125I-IL
      6 binding in U266 cells. Delineation of this domain identified 249Y10R258 as the
      minimum effective sequence capable of inhibiting fibrinogen synthesis. Amino acid
      substitutions in 249Y10R258 obliterated the inhibitory effect on fibrinogen
      synthesis. In conclusion, a region of the extramembranous domain of the IL-6R has
      been identified that is involved in the regulation of IL-6 signal transmission. A
      synthetic peptide representing this region inhibits IL-6-dependent B9 cell
      mitogenesis and IL-6-stimulated acute phase response in HepG2 cells without
      affecting ligand binding.

PMID- 7519614
TI  - Cloning and characterization of alternatively spliced isoforms of rat tenascin.
      Platelet-derived growth factor-BB markedly stimulates expression of spliced
      variants of tenascin mRNA in arterial smooth muscle cells.
AB  - To understand the alteration of extracellular matrix composition evoked by
      chemotactic factors, we have studied the expression of adhesive (fibronectin) and
      anti-adhesive (tenascin) proteins in response to platelet-derived growth factor
      BB (PDGF-BB), a potent chemoattractant for rat aortic smooth muscle cells (ASMC).
      PDGF-BB markedly induced two major tenascin mRNA transcripts, whereas fibronectin
      mRNA levels did not change. The results of immunoprecipitation studies paralleled
      Northern blot data. Since alternative splicing is responsible for the generation
      of multiple tenascin mRNAs in other cell types, we studied the effect of
      chemotactic factors on the relative abundance of tenascin isoforms. The
      alternatively spliced region of ASMC-derived rat tenascin was amplified and the
      identity of the products confirmed by sequencing. Three major polymerase chain
      reaction products were detected: a 1727-base pair unspliced form which was
      maximal at 2 h and 635- and 362-base pair products which were more abundant at 8
      h after treatment with PDGF-BB or angiotensin II. Functional studies showed that
      the unspliced isoform of human tenascin inhibited attachment of both human and
      rat ASMC to fibronectin. These results suggest that PDGF-BB markedly up-regulates
      the expression of tenascin variants, which may lead to destabilization of cell
      matrix interactions and promotion of cell migration.

PMID- 7519616
TI  - Stable expression of heterologous microtubule-associated proteins (MAPs) in
      Chinese hamster ovary cells: evidence for differing roles of MAPs in microtubule
      organization.
AB  - To study the effects of microtubule-associated proteins (MAPs) on in vivo
      microtubule assembly, cDNAs containing the complete coding sequences of a
      Drosophila 205-kD heat stable MAP, human MAP 4, and human tau were stably
      transfected into CHO cells. Constitutive expression of the transfected genes was
      low in most cases and had no obvious effects on the viability of the transfected
      cell lines. High levels of expression, as judged by Western blots,
      immunofluorescence, and Northern blots, could be induced by treating cells with
      sodium butyrate. High levels of MAPs were maintained for at least 24-48 h after
      removal of the sodium butyrate. Immunofluorescence analysis indicated that all
      three MAPs bound to cellular microtubules, but only the transfected tau caused a
      rearrangement of microtubules into bundles. Despite high levels of expression of
      these exogenous MAPs and the bundling of microtubules in cells expressing tau,
      transfected cells had normal levels of assembled and unassembled tubulin. With
      the exception of the tau-induced bundles, microtubules in transfected cells
      showed the same sensitivity as control cells to microtubule depolymerization by
      Colcemid. Further, all three MAPs were ineffective in reversing the taxol
      dependent phenotype of a CHO mutant cell line. The absence of a quantitative
      effect of any of these heterologous proteins on the assembly of tubulin suggests
      that these MAPs may have different roles in vivo from those inferred previously
      from in vitro experiments.

PMID- 7519617
TI  - Phosphorylation on carboxyl terminus domains of neurofilament proteins in retinal
      ganglion cell neurons in vivo: influences on regional neurofilament accumulation,
      interneurofilament spacing, and axon caliber.
AB  - The high molecular weight subunits of neurofilaments, NF-H and NF-M, have
      distinctively long carboxyl-terminal domains that become highly phosphorylated
      after newly formed neurofilaments enter the axon. We have investigated the
      functions of this process in normal, unperturbed retinal ganglion cell neurons of
      mature mice. Using in vivo pulse labeling with [35S]methionine or
      [32P]orthophosphate and immunocytochemistry with monoclonal antibodies to
      phosphorylation-dependent neurofilament epitopes, we showed that NF-H and NF-M
      subunits of transported neurofilaments begin to attain a mature state of
      phosphorylation within a discrete, very proximal region along optic axons
      starting 150 microns from the eye. Ultrastructural morphometry of 1,700-2,500
      optic axons at each of seven levels proximal or distal to this transition zone
      demonstrated a threefold expansion of axon caliber at the 150-microns level,
      which then remained constant distally. The numbers of neurofilaments nearly
      doubled between the 100- and 150-microns level and further increased a total of
      threefold by the 1,200-microns level. Microtubule numbers rose only 30-35%. The
      minimum spacing between neurofilaments also nearly doubled and the average
      spacing increased from 30 nm to 55 nm. These results show that carboxyl-terminal
      phosphorylation expands axon caliber by initiating the local accumulation of
      neurofilaments within axons as well as by increasing the obligatory lateral
      spacing between neurofilaments. Myelination, which also began at the 150-microns
      level, may be an important influence on these events because no local
      neurofilament accumulation or caliber expansion occurred along unmyelinated optic
      axons. These findings provide evidence that carboxyl-terminal phosphorylation
      triggers the radial extension of neurofilament sidearms and is a key regulatory
      influence on neurofilament transport and on the local formation of a stationary
      but dynamic axonal cytoskeletal network.

PMID- 7519618
TI  - The cytoplasmic domain of the myelin P0 protein influences the adhesive
      interactions of its extracellular domain.
AB  - The extracellular domain of the myelin P0 protein is believed to engage in
      adhesive interactions and thus hold the myelin membrane compact. We have
      previously shown that P0 can behave as a homophilic adhesion molecule through
      interactions of its extracellular domains (Filbin, M. T., F. S. Walsh, B. D.
      Trapp, J. A. Pizzey, and G. I. Tennekoon. 1990. Nature (Lond.) 344:871-872). To
      determine if the cytoplasmic domain of P0 must be intact for the extracellular
      domains to adhere, we compared the adhesive capabilities of P0 proteins truncated
      at the COOH-terminal to the full-length P0 protein. P0 cDNAs lacking nucleotides
      coding for the last 52 or 59 amino acids were transfected into CHO cells, and
      surface expression of the truncated proteins was assessed by immunofluorescence,
      surface labeling followed by immunoprecipitation, and an ELISA. Cell lines were
      chosen that expressed at least equivalent amounts of the truncated P0 proteins at
      the surface as did a cell line expressing the full-length P0. The adhesive
      properties of these three cell lines were compared. It was found that when a
      suspension of single cells was allowed to aggregate for a period of 60 min, only
      the cells expressing the full-length P0 had formed large aggregates, while the
      cells expressing the truncated P0 molecules were still mostly single cells
      indistinguishable from the control cells. Furthermore, 25-30% of the full-length
      P0 was insoluble in NP40, indicative of an interaction with the cytoskeleton,
      whereas only 5-10% of P0 lacking 52 amino acids and none of P0 lacking 59 amino
      acids were insoluble. These results suggest that for the extracellular domain of
      P0 to behave as a homophilic adhesion molecule, its cytoplasmic domain must be
      intact, and most probably, it is interacting with the cytoskeleton.

PMID- 7519619
TI  - Ankyrin-binding domain of CD44(GP85) is required for the expression of hyaluronic
      acid-mediated adhesion function.
AB  - GP85 is one of the most common hemopoietic isoforms of the cell adhesion
      molecule, CD44. CD44(GP85) is known to contain at least one ankyrin-binding site
      within its 70 aa cytoplasmic domain and to bind hyaluronic acid (HA) with its
      extracellular domain. In this study we have mapped the ankyrin-binding domain of
      CD44(GP85) by deleting various portions of the cytoplasmic region followed by
      expression of these truncated cDNAs in COS cells. The results of these
      experiments indicate that the ankyrin-binding domain resides between amino acids
      305 and 355. Biochemical analyses, using competition binding assays and a
      synthetic peptide (NGGNGT-VEDRKPSEL) containing 15 aa between aa 305 and aa 320,
      support the conclusion that this region is required for ankryin binding.
      Furthermore, we have constructed a fusion protein in which this 15 aa sequence of
      CD44(GP85) is transplanted onto another transmembrane protein which does not bind
      ankyrin. Our results show that this fusion protein acquires the ability to bind
      ankyrin confirming that the sequence (306NGGNGTVEDRKPSE320L) is a critical part
      of the ankryin-binding domain of CD44(GP85). In addition, we have demonstrated
      that deletion of this 15 aa ankyrin-binding sequence from CD44(GP85) results in a
      drastic reduction (> or = 90%) of HA-binding and HA-mediated cell adhesion. These
      findings strongly suggest that ankyrin binding to the cytoplasmic domain of
      CD44(GP85) plays a pivotal role in regulating hyaluronic acid-mediated cell-cell
      and cell-extracellular matrix interactions.

PMID- 7519620
TI  - Beta 2 integrin-dependent protein tyrosine phosphorylation and activation of the
      FGR protein tyrosine kinase in human neutrophils.
AB  - Stimulation of adherent human neutrophils (PMN) with tumor necrosis factor (TNF)
      triggers protein tyrosine phosphorylation (Fuortes, M., W. W. Jin, and C. Nathan.
      1993. J. Cell Biol. 120:777-784). We investigated the dependence of this response
      on beta 2 integrins by using PMN isolated from a leukocyte adhesion deficiency
      (LAD) patient, which do not express beta 2 integrins, and by plating PMN on
      surface bound anti-beta 2 (CD18) antibodies. Protein tyrosine phosphorylation
      increased in PMN plated on fibrinogen and this phosphorylation was enhanced by
      TNF. Triggering of protein tyrosine phosphorylation did not occur in LAD PMN
      plated on fibrinogen either in the absence or the presence of TNF. Surface bound
      anti-CD18, but not isotype-matched anti-Class I major histocompatibility complex
      (MHC) antigens, antibodies triggered tyrosine phosphorylation in normal, but not
      in LAD PMN. As the major tyrosine phosphorylated proteins we found in our assay
      conditions migrated with an apparent molecular mass of 56-60 kD, we investigated
      whether beta 2 integrins are implicated in activation of members of the src
      family of intracellular protein-tyrosine kinases. We found that the fgr protein
      tyrosine kinase (p58fgr) activity, and its extent of phosphorylation in tyrosine,
      in PMN adherent to fibrinogen, was enhanced by TNF. Activation of p58fgr in
      response to TNF was evident within 10 min of treatment and increased with times
      up to 30 min. Also other activators of beta 2 integrins such as phorbol-12
      myristate 13-acetate (PMA), and formyl methionyl-leucyl-phenylalanine (FMLP),
      induced activation of p58fgr kinase activity. Activation of p58fgr kinase
      activity, and phosphorylation in tyrosine, did not occur in PMN of a LAD patient
      in response to TNF. Soluble anti-CD18, but not anti-Class I MHC antigens,
      antibodies inhibited activation of p58fgr kinase activity in PMN adherent to
      fibrinogen in response to TNF, PMA, and FMLP. These findings demonstrate that, in
      PMN, beta 2 integrins are implicated in triggering of protein tyrosine
      phosphorylation, and establish a link between beta 2 integrin-dependent adhesion
      and the protein tyrosine kinase fgr in cell signaling.

PMID- 7519623
TI  - Fluorescence photooxidation with eosin: a method for high resolution
      immunolocalization and in situ hybridization detection for light and electron
      microscopy.
AB  - A simple method is described for high-resolution light and electron microscopic
      immunolocalization of proteins in cells and tissues by immunofluorescence and
      subsequent photooxidation of diaminobenzidine tetrahydrochloride into an
      insoluble osmiophilic polymer. By using eosin as the fluorescent marker, a
      substantial improvement in sensitivity is achieved in the photooxidation process
      over other conventional fluorescent compounds. The technique allows for precise
      correlative immunolocalization studies on the same sample using fluorescence,
      transmitted light and electron microscopy. Furthermore, because eosin is smaller
      in size than other conventional markers, this method results in improved
      penetration of labeling reagents compared to gold or enzyme based procedures. The
      improved penetration allows for three-dimensional immunolocalization using high
      voltage electron microscopy. Fluorescence photooxidation can also be used for
      high resolution light and electron microscopic localization of specific nucleic
      acid sequences by in situ hybridization utilizing biotinylated probes followed by
      an eosin-streptavidin conjugate.

PMID- 7519622
TI  - In vivo analysis of the stability and transport of nuclear poly(A)+ RNA.
AB  - We have studied the distribution of poly(A)+ RNA in the mammalian cell nucleus
      and its transport through nuclear pores by fluorescence and electron microscopic
      in situ hybridization. Poly(A)+ RNA was detected in the nucleus as a speckled
      pattern which includes interchromatin granule clusters and perichromatin fibrils.
      When cells are fractionated by detergent and salt extraction as well as DNase I
      digestion, the majority of the nuclear poly(A)+ RNA was found to remain
      associated with the nonchromatin RNP-enriched fraction of the nucleus. After
      inhibition of RNA polymerase II transcription for 5-10 h, a stable population of
      poly(A)+ RNA remained in the nucleus and was reorganized into fewer and larger
      interchromatin granule clusters along with pre-mRNA splicing factors. This stable
      population of nuclear RNA may play an important role in nuclear function.
      Furthermore, we have observed that, in actively transcribing cells, the regions
      of poly(A)+ RNA which reached the nuclear pore complexes appeared as narrow
      concentrations of RNA suggesting a limited or directed pathway of movement. All
      of the observed nuclear pores contained poly(A)+ RNA staining suggesting that
      they are all capable of exporting RNA. In addition, we have directly visualized,
      for the first time in mammalian cells, the transport of poly(A)+ RNA through the
      nuclear pore complexes.

PMID- 7519626
TI  - Development of an assay that detects transcriptionally competent human
      immunodeficiency virus type one particles.
AB  - To study the functional properties of HIV-1 reverse transcriptase (RT) from
      intact viral particles without the requirement for tissue culture expansion, a
      method that couples HIV-1 reverse transcription utilizing its endogenous RT (ERT)
      with polymerase chain reaction amplification (PCR) was developed. Detection of
      endogenous reverse transcripts from HIV particles by ERT-PCR was compared to HIV
      RNA PCR detection using avian myeloblastosis virus (AMV) RT from plasma samples
      from 45 HIV-1 infected patients. The HIV ERT-PCR method was capable of detecting
      plasma viremia with the same efficiency (29/29 patients) as the AMV RT HIV RNA
      PCR in patients with CD4 cell counts of less than 500/mm3. The determination of
      HIV-RT drug sensitivities using four well-characterized HIV-1 lab strains was
      assessed. The ERT-PCR method detected reduced sensitivity to TIBO R82150 (10
      microM) in a TIBO resistant strain but not in the TIBO sensitive HTLV-IIIB viral
      mixture or an HTLV-IIIB clone. In summary, the HIV ERT-PCR method provides a
      useful approach for the detection of HIV and the characterization of RT
      sensitivities among HIV-1 strains.

PMID- 7519624
TI  - Dictyostelium discoideum mutants with conditional defects in phagocytosis.
AB  - We have isolated and characterized Dictyostelium discoideum mutants with
      conditional defects in phagocytosis. Under suspension conditions, the mutants
      exhibited dramatic reductions in the uptake of bacteria and polystyrene latex
      beads. The initial binding of these ligands was unaffected, however, indicating
      that the defect was not in a plasma membrane receptor: Because of the
      phagocytosis defect, the mutants were unable to grow when cultured in suspensions
      of heat-killed bacteria. The mutants exhibited normal capacities for fluid phase
      endocytosis and grew as rapidly as parental (AX4) cells in axenic medium. Both
      the defects in phagocytosis and growth on bacteria were corrected when the mutant
      Dictyostelium cells were cultured on solid substrates. Reversion and genetic
      complementation analysis suggested that the mutant phenotypes were caused by
      single gene defects. While the precise site of action of the mutations was not
      established, the mutations are likely to affect an early signaling event because
      the binding of bacteria to mutant cells in suspension was unable to trigger the
      localized polymerization of actin filaments required for ingestion; other aspects
      of actin function appeared normal. This class of conditional phagocytosis mutant
      should prove to be useful for the expression cloning of the affected gene(s).

PMID- 7519621
TI  - Alternative splicing introduces a nuclear localization signal that targets
      multifunctional CaM kinase to the nucleus.
AB  - Intracellular targeting may enable protein kinases with broad substrate
      specificities, such as multifunctional Ca2+/calmodulin-dependent protein kinase
      (CaM kinase) to achieve a selectivity of action in vivo. We have examined the
      intracellular targeting of three delta-CaM kinase isoforms. The delta B-CaM
      kinase isoform is targeted to the nucleus in transfected cells while the delta A-
      and delta C-CaM kinase isoforms are cytosolic/cytoskeletal. A chimeric construct
      of alpha-CaM kinase containing the delta B-CaM kinase variable domain is rerouted
      to the nucleus while the native alpha-CaM kinase and chimeras of alpha-CaM kinase
      which contain the delta A- or delta C-CaM kinase variable domains are retained in
      the cytoplasm. Using site-directed mutagenesis, we have defined a nuclear
      localization signal (NLS) within an 11-amino acid sequence, likely inserted by
      alternative splicing, in the variable domain of delta B-CaM kinase. Isoform
      specific nuclear targeting of CaM kinase is probably a key mechanism in the
      selective regulation of nuclear functions by CaM kinase. CaM kinase is a multimer
      that can be composed of several isoforms. We find that when cells express two
      different isoforms of CaM kinase, cellular targeting is determined by the ratio
      of the isoforms. When an excess of the cytoplasmic isoform of CaM kinase is
      coexpressed along with the nuclear isoform, both isoforms are localized in the
      cytoplasm. Conversely an excess of the nuclear isoform can reroute the
      cytoplasmic isoform to the nucleus. The nuclear isoform likely coassembles with
      the cytosolic isoform, to form a heteromultimeric holoenzyme which is transported
      into the nucleus. These experiments demonstrate isoform-specific targeting of CaM
      kinase and indicate that such targeting can be modified by the expression of
      multiple isoforms of the enzyme.

PMID- 7519627
TI  - The mycoplasma-related inhibitor of HIV-1 reverse transcriptase has a DNase
      activity and is present in the particle-free supernatants of contaminated
      cultures.
AB  - Drastic inhibition of the human immunodeficiency virus (HIV) reverse
      transcriptase (RT) by mycoplasma has been noted in many laboratories causing
      confusion in data interpretation. The mycoplasma-related inhibitor of HIV-1 RT
      was identified as a soluble protein in the particle-free supernatant of a
      contaminated culture. Gel filtration studies revealed the molecular mass of this
      protein to be about 70 kDa. This RT-inhibitor contained a DNase with strong
      activity on both linear and circular DNAs. Addition of this inhibitor after
      completion of reverse transcription still reduced the final outcome of the RT
      assay significantly, implying that the inhibitory mechanism occurred mainly by
      its DNase activity. Treatment of the culture with an antimycoplasma drug cured
      the mycoplasma contamination, removed the RT-inhibitor and abolished the DNase
      activity.

PMID- 7519625
TI  - A double leucine within the GLUT4 glucose transporter COOH-terminal domain
      functions as an endocytosis signal.
AB  - The unique COOH-terminal 30-amino acid region of the adipocyte/skeletal muscle
      glucose transporter (GLUT4) appears to be a major structural determinant of this
      protein's perinuclear localization, from where it is redistributed to the cell
      surface in response to insulin. To test whether an underlying mechanism of this
      domain's function involves glucose transporter endocytosis rates, transfected
      cells were generated expressing exofacial hemagglutinin epitope (HA)-tagged
      erythrocyte/brain glucose transporter (GLUT1) or a chimera containing the COOH
      terminal 30 amino acids of GLUT4 substituted onto this GLUT1 construct.
      Incubation of COS-7 or CHO cells expressing the HA-tagged chimera with anti-HA
      antibody at 37 degrees resulted in an increased rate of antibody internalization
      compared to cells expressing similar levels of HA-tagged GLUT1, which displays a
      cell surface disposition. Colocalization of the internalized anti-HA antibody in
      vesicular structures with internalized transferrin and with total transporters
      was established by digital imaging microscopy, suggesting the total cellular pool
      of transporters are continuously recycling through the coated pit endocytosis
      pathway. Mutation of the unique double leucines 489 and 490 in the rat GLUT4 COOH
      terminal domain to alanines caused the HA-tagged chimera to revert to the slow
      endocytosis rate and steady-state cell surface display characteristic of GLUT1.
      These results support the hypothesis that the double leucine motif in the GLUT4
      COOH terminus operates as a rapid endocytosis and retention signal in the GLUT4
      transporter, causing its localization to intracellular compartments in the
      absence of insulin.

PMID- 7519628
TI  - Isolation and characterization by immunofluorescence, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, western blot, restriction fragment length
      polymorphism-PCR, 16S rRNA gene sequencing, and pulsed-field gel electrophoresis
      of Rochalimaea quintana from a patient with bacillary angiomatosis.
AB  - Rochalimaea quintana was isolated from the blood of a French human
      immunodeficiency virus-infected patient with bacillary angiomatosis. The isolate
      showed the typical growth characteristics of Rochalimaea species and was inert
      when typical biochemical testing was used. The purpose of the present work was to
      characterize and compare this new isolate with reference strains of R. quintana,
      Rochalimaea vinsonii, and Rochalimaea henselae by using immunofluorescence,
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western
      blot (immunoblot), restriction fragment length polymorphism-PCR of the citrate
      synthase gene, 16S rRNA gene sequencing, and pulsed-field gel electrophoresis.
      SDS-PAGE, Western blot, restriction fragment length polymorphism-PCR with TaqI
      enzyme, and 16S rRNA gene sequencing could differentiate the three Rochalimaea
      species and allowed characterization of the French isolate as R. quintana.
      However, identification of the Rochalimaea isolate to the species level was more
      easily obtained by immunofluorescence with specific murine antisera. Pulsed-field
      gel electrophoresis allowed differentiation of the French R. quintana isolate
      from R. quintana Fuller and may serve as an epidemiological tool.

PMID- 7519629
TI  - Detection of Pseudomonas pseudomallei by PCR and hybridization.
AB  - A molecular method for the detection of Pseudomonas pseudomallei was developed on
      the basis of the differences in the 23S rRNA sequences of related species of the
      genus Pseudomonas. An 18-base oligonucleotide probe, designed following partial
      sequencing of 23s ribosomal DNA (rDNA), was used for the identification and
      detection of P. pseudomallei either by hybridization or by direct PCR. Optimal
      detection was obtained by hybridization of the probe with PCR-amplified rDNA
      rather than with total genomic DNA or colony blots. One nanogram of template DNA
      amplified in a PCR mixture containing 14% glycerol could be detected in slot
      blots hybridized with the digoxigenin-labelled probe and the lumigen PPD
      detection system. Amplified rDNA sequences from 41 P. pseudomallei strains of
      various origins hybridized with the probe. The probe also hybridized with three
      Pseudomonas mallei reference strains under conditions of high stringency but
      failed to hybridize with amplified rDNA sequences from other closely related
      Pseudomonas spp. PCR with a conserved primer and the 18-base oligonucleotide
      probe (direct PCR) specifically amplified P. pseudomallei and P. mallei. By using
      these methods, approximately 10(4) P. pseudomallei cells per ml could be detected
      in artificially inoculated blood samples and in blood dried on filter paper
      following Chelex extraction. The detection limit in blood was increased to 10(2)
      cells per ml by concentration of bacteria from 0.5 ml of blood or by a 24-h blood
      culture enrichment prior to PCR. Approximately 10(3) cells per ml were detected
      in seeded sputum samples. The detection times by direct PCR and indirect PCR and
      then probe hybridization were approximately 5 h and 24 h, respectively. These
      results indicate that amplification of conserved rDNA sequences by PCR directly
      or by hybridization with a probe to PCR fragments offers promise for the
      detection of P. pseudomallei and P. mallei.

PMID- 7519630
TI  - Use of PCR with feces for detection of Helicobacter pylori infections in
      patients.
AB  - PCR was performed for the detection of Helicobacter pylori in feces from 24
      patients with proven infections. Several precautions were taken to overcome
      possible inhibition of PCR with feces. In the first 12 patients, feces were
      examined shortly after endoscopy. In another group of 12 patients, who were
      treated during 2 weeks with omeprazole (40 mg each day) to increase gastric pH,
      feces were examined as well. H. pylori target DNA could not be detected in the
      stools of any of the 24 infected patients. It was concluded that there was no
      substantial shedding of H. pylori in feces from either group of patients.

PMID- 7519631
TI  - Significance of highly positive c22-3 "indeterminate" second-generation hepatitis
      C virus (HCV) recombinant immunoblot assay (RIBA) and resolution by third
      generation HCV RIBA.
AB  - Second-generation recombinant immunoblot assay (RIBA) is widely used for the
      validation of anti-hepatitis C virus (HCV) antibody detection. The aims of this
      work were (i) to determine, in terms of liver disease and HCV replication, the
      significance of a peculiar "indeterminate" second-generation RIBA pattern
      characterized by the presence of high titers of antibodies directed to c22-3, a
      protein bearing core epitopes and (ii) to determine whether a more advanced
      version of the same strip assay, namely a third-generation RIBA, may solve the
      problem of such indeterminate patterns. Sixty patients for which c22-3
      indeterminate second-generation RIBAs were highly positive were studied. Forty
      two of them (70%) were immunocompromised. Serum transaminases were increased in
      46 cases (77%), and HCV RNA was detected by PCR in 50 cases (83%). Third
      generation RIBA remained highly positive c22 indeterminate for 9 patients (15%)
      but was positive for 51 (85%), mostly because of increased sensitivity for the
      detection of both anti-c100 and anti-c33c antibodies. These results suggest that
      third-generation RIBA may achieve resolution of most of these cases but that
      highly positive c22 indeterminate third-generation RIBA may persist when used
      with some patients with very low titers of anti-HCV nonstructural protein
      antibodies.

PMID- 7519632
TI  - Interferon gamma up-regulates alpha 2 macroglobulin expression in human
      astrocytoma cells.
AB  - An established human astrocytoma cell line (T67) was shown to constitutively
      produce the proteinase inhibitor alpha 2 macroglobulin (alpha 2M). Interferon
      gamma (IFN gamma), a potent immunoregulatory lymphokine, was able to increase the
      synthesis of alpha 2M by these cells, as measured by ELISA on cell supernatants.
      The alpha 2M induction was also observed in other human glioma cell lines (T70
      and ADF) and in human fetal astrocyte cultures following IFN gamma treatment. In
      T67 cells this effect was dose-dependent and the maximum (2.7-fold increase) was
      obtained with 2000 U/ml of IFN gamma. A corresponding enhanced alpha 2M mRNA
      accumulation was demonstrated by PCR and Northern blot techniques. Our results
      suggest an important role of alpha 2M during inflammatory and immune processes in
      the CNS. An increased release of alpha 2M following IFN gamma stimulation may
      allow the removal of the bulk of proteases released at the site of inflammation,
      strengthening at the same time the antigen presentation processes.

PMID- 7519633
TI  - T cell immunity to myelin basic protein induces anterior uveitis in Lewis rats.
AB  - Uveitis of unknown etiology is known to occur in association with various
      systemic disorders. We now report that anterior uveitis (AU) can be produced by T
      cell immunity to myelin basic protein (BP) and accompanies experimental
      autoimmune encephalomyelitis (EAE). EAE with AU was induced in Lewis rats by
      immunization to BP in CFA or by immunization to various BP peptides including the
      encephalitogenic 71-90 peptide. Slit-lamp biomicroscopy of BP-immunized Lewis
      rats revealed AU, characterised by inflammation of the iris, in 73% of the eyes.
      The onset of AU in actively immunized rats varied between days 12 and 26, often
      appearing after spontaneous remission of the paralysis, the hallmark of EAE. The
      course of AU was progressive, affecting more than 50% of the surface of the iris
      in 16 of 29 diseased eyes. Like the paralysis, the AU was self-limiting: within 2
      weeks the disease remitted. In addition, AU could be adoptively transferred to
      naive and irradiated rats by a T cell clone specific for BP peptide 71-90. The
      present observations are compatible with the idea that AU may be triggered by BP
      reactive T cells. The myelinated nerves present in the iris have been shown to
      contain BP. However, these peripheral nerves would now appear to be the only
      peripheral nerves susceptible to acute EAE.

PMID- 7519634
TI  - Sounds triggers spikes in the Landau-Kleffner syndrome.
AB  - Auditory evoked magnetic fields and spontaneous epileptic activity were recorded
      with a 24-channel planar gradiometer in 7 children with acquired epileptic speech
      disorders. Six children had a marked loss of speech comprehension (the Landau
      Kleffner syndrome--LKS); in one child, only the speech fluency was affected.
      Auditory evoked fields were abnormal in five patients studied during active
      disease. Sounds triggered signals identical to the spontaneous spikes in three
      LKS patients. In two patients, the triggered spikes lagged the tone onset by 100
      ms, whereas the interstimulus interval affected the lag in the third. The neural
      generator sites of spontaneous and triggered spikes did not differ: both were
      within a 2-6-cm2 patch of cortex aligning the sylvian fissure in one or both
      hemispheres. The epileptiform activity of LKS patients may be produced by sound
      responsive neurons in the nonprimary auditory cortex within the middle and
      posterior sylvian fissures. The generators of the auditory 100-ms response
      probably contribute to the spikes in a group of LKS patients, but other
      pathogenetic mechanisms may coexist.

PMID- 7519636
TI  - Hazards of interferon treatment in patients with autoimmune chronic active
      hepatitis.

PMID- 7519635
TI  - Hepatitis C infection unrelated to blood transfusion in hemodialysis patients.
AB  - Hepatitis C virus antibodies were studied using both the 1st and 2nd generation
      tests in 485 patients who were on maintenance hemodialysis. One hundred and
      eighty-seven tested positive for antibodies (38.6%); 139 of them had a history of
      past blood transfusion. There was a crude correlation between the amount of blood
      given and the antibody positivity rate among those who had a history of blood
      transfusion. Of 152 patients who had no blood transfusion history, 48 or 31.2%
      were positive for the antibodies. The length of the period during which these
      patients had undergone dialysis was closely correlated with the positivity rate;
      50% of those who had been on dialysis for more than 10 years were positive for
      anti-HCV. The positivity rate among the new dialysis patients with chronic renal
      failure as the control was 4.6%. The difference may be accounted for by
      nosocomial hepatitis C virus infection. It appears that with two new needle holes
      made along the anastomosed blood vessels two to three times a week, the chances
      of patient exposure to hepatitis C virus may increase with time.

PMID- 7519638
TI  - Differential up-regulation of the B7-1 and B7-2 costimulatory molecules after Ig
      receptor engagement by antigen.
AB  - Ag-pulsed B cells are potent APCs, in part, because of the ability of the Ig
      receptor to mediate rapid and specific Ag uptake. However, it is also known that
      full T cell activation requires signals delivered by costimulatory molecules,
      which naive B cells seem to lack. This study examines the effect Ig receptor
      engagement has on the expression and function of a new CD28 counter-receptor, B7
      2. Unlike B7-1 (B7), B7-2 was rapidly induced on the cell surface of B cells
      after engagement of the Ig receptor by either anti-Ig mAbs or hen egg lysozyme
      (HEL) on normal and HEL-specific B cell receptor transgenic B cells,
      respectively. Furthermore, B7-2 expression was up-regulated on tolerant B cells
      isolated from HEL/anti-HEL double transgenic mice after Ag stimulation, although
      at lower levels than on nontolerant transgenic B cells. No significant cell
      surface levels of B7-1(B7) were observed under these conditions. Finally, the B7
      2 molecules induced by Ig cross-linking costimulated T cell proliferation in a
      CD28-dependent manner, independent of B7-1(B7) expression. Thus, the
      effectiveness of Ag-specific B cells as APCs depends on both their enhanced Ag
      uptake, mediated by the B cell receptor, and immediate up-regulation of a potent
      costimulatory molecule, B7-2.

PMID- 7519637
TI  - Tyrosine kinase activation provides an early and requisite signal for Fas-induced
      apoptosis.
AB  - Selective cell death plays a critical role in the development of the immune
      repertoire and in the elimination of target cells expressing foreign Ags. The
      apoptosis induced by ligation of the Fas Ag, a member of the TNFR/nerve growth
      factor receptor superfamily, contributes to both of these modes of cell loss.
      However, in spite of the molecular cloning of the Fas Ag and the identification
      of a specific cytoplasmic domain required for its function, it remains unclear as
      to which Fas-induced second messengers mediate the development of programmed cell
      death. We, therefore, evaluated Fas-initiated signal transduction in susceptible
      cell types. We determined that Fas ligation induces the rapid tyrosine
      phosphorylation of multiple cellular proteins. These phosphorylation events occur
      within 1 min and decline toward baseline by 30 min. In addition, Fas ligation
      increases the in vitro protein kinase activity of the tyrosine phosphorylated
      proteins. Pharmacologic inhibitors of protein tyrosine kinases block, in a
      concentration-dependent manner, Fas-induced DNA fragmentation and prolong cell
      survival. These results suggest that protein tyrosine kinase activation is an
      early and obligatory signal in Fas-induced apoptosis.

PMID- 7519639
TI  - CD1+ human thymocytes proliferate in response to superantigen staphylococcal
      enterotoxin B1.
AB  - Exposure of human thymocytes to superantigens results in the deletion of
      thymocytes expressing specific TCR-V beta genes. The factors that contribute to
      this deletion may relate to the inherent nature of the T cell at a given stage of
      development. In this paper, we demonstrate that CD1+ human cortical thymocytes
      are capable of proliferating in response to a bacterial superantigen
      (staphylococcal enterotoxin B (SEB)) in the presence of autologous CD2-/low
      thymic APCs. Phenotypic analysis of the responding populations revealed that the
      majority of the CD1+ cells were CD4+CD8low or CD8+CD4low cells. The response is
      triggered by low concentrations of SEB, requires the participation of the TCR and
      IL-2R molecules, and is inhibited by cyclosporin A. Thymocytes that express
      specific V beta genes are expanded, which results in an engagement profile that
      parallels that found in PBLs. Additionally, four V beta-chains that have not been
      reported previously are shown to engage SEB. Once stimulated, the thymocytes
      failed to respond to additional SEB; however, they could be induced to
      proliferative with IL-2, which suggests that these expanded populations had
      become anergic. These data represent the first demonstration of a human cortical
      thymocyte subpopulation that responds to superantigen by proliferation and
      subsequent anergy.

PMID- 7519642
TI  - Eosinophil transendothelial migration induced by cytokines. III. Effect of the
      chemokine RANTES.
AB  - Selective eosinophil recruitment occurs after experimental Ag challenge and in
      tissue sites of allergic diseases. The mechanisms of selective eosinophil
      migration are still unknown. In our study, we examined the ability of chemokines
      to induce transendothelial migration (TEM) of eosinophils in vitro. Among the
      chemokines tested, only RANTES induced eosinophil TEM. RANTES failed to induce
      TEM of neutrophils. Interestingly, IL-8 induced neutrophil TEM and had no effect
      on eosinophil TEM. RANTES-induced TEM was concentration-dependent and was
      inhibited by Abs directed against the beta 2 integrin CD18. When IL-1-activated
      endothelial cells were utilized, RANTES-induced TEM also involved the eosinophil
      beta 1 integrin VLA-4. RANTES did not increase eosinophil adhesion to either
      resting or IL-1-activated endothelial cells, nor did the chemokine increase CD11b
      or decrease L-selectin expression. A gradient of RANTES appears to be required
      for eosinophil TEM. Pre-exposure of eosinophils to IL-5 dramatically potentiated
      the TEM response to RANTES. These findings suggest that the chemokine RANTES is a
      potent and selective inducer of eosinophil TEM. Because RANTES appears to be
      produced in vivo during allergic reactions or in allergic diseases, we speculate
      that these findings may have some direct relevance to the mechanism of selective
      eosinophil recruitment in vivo in humans.

PMID- 7519641
TI  - Effect of aging on murine macrophages. Diminished response to IFN-gamma for
      enhanced oxidative metabolism.
AB  - The ability of macrophages to secrete reactive oxygen intermediates, as well as
      reactive nitrogen intermediates, correlates closely with their capacity to
      perform two critical effector functions: intracellular killing of microorganisms
      and lysis of tumor cells. In this study, age-associated changes in the ability of
      caseinate-elicited peritoneal macrophages to release hydrogen peroxide were
      determined. Macrophages from aged BALB/c mice produced 50% less hydrogen peroxide
      than those from young mice in response to PMA or opsonized zymosan. In contrast,
      the production of macrophage-activating cytokines including IFN-gamma was not
      diminished in splenocyte supernatants from the aged group. Furthermore, no
      difference was detected in surface expression of IFN-gamma receptor in old and
      young mice. Macrophage responses to IFN-gamma, however, declined with aging. In
      vitro, IFN-gamma-induced release of hydrogen peroxide and nitric oxide was 50%
      lower in old mice than in young mice. IFN-gamma-induced tyrosine phosphorylation
      of MAPK, an early activation event, was undetectable in macrophages from the aged
      mice. These data demonstrate that diminished responses of macrophages to
      activating signals are one aspect of the impaired immune response in aged mice.

PMID- 7519640
TI  - Different signaling pathways for CD18-mediated adhesion and Fc-mediated
      phagocytosis. Response of neutrophils to LPS.
AB  - The regulation of CD11b/CD18 adhesive and phagocytic functions on human
      polymorphonuclear leukocytes (PMN) in response to LPS was examined. Adhesion of
      PMN to surfaces coated with LPS had little or no effect on the cells, but
      pretreating the LPS-coated surfaces with either diluted serum or LPS-binding
      protein strongly enhanced their ability to bind C3bi-coated E (EC3bi), a ligand
      for CD11b/CD18. LPS-binding protein is known to enable responses of cells to LPS
      by facilitating binding of LPS to CD14. Consistent with this, we found that
      preformed complexes of LPS with soluble rCD14 stimulated binding of ligand by
      CD11b/CD18 in a concentration-dependent manner. Known agonists that stimulate
      CD11b/CD18 binding activity on PMN all cause simultaneous enhancement of Fc
      mediated phagocytosis. However, LPS presented in complex with either serum
      proteins or CD14 failed to stimulate the ingestion of ElgG by PMN. The number of
      FcRs and their ability to bind ligand were not affected by treatment with LPS,
      nor were they compromised in their ability to respond to other agonists. These
      results suggest that LPS generates intracellular signals that alter the ability
      of CD11b/CD18 to bind ligand, but this alteration is not sufficient to promote
      phagocytosis of IgG-coated particle. This conclusion was confirmed by showing
      that PMN treated with LPS and serum produced a lipid with the properties of
      integrin-modulating factor 1: acetone extracts of these cells stimulated
      CD11b/CD18 adhesive capacity on PMN. However, the lipid did not enhance Fc
      mediated phagocytosis. These studies suggest that CD14 affects CD11b/CD18
      function by inducing the synthesis of a lipid such as IMF-1, and that this lipid
      affects only the binding activity, not the phagocytosis-promoting capacity of
      CD11b/CD18.

PMID- 7519643
TI  - Comparison of human eosinophil and neutrophil adhesion to endothelial cells under
      nonstatic conditions. Role of L-selectin.
AB  - To simulate adhesion that occurs under conditions of flow, we investigated the
      attachment of eosinophils to endothelium under rotational conditions. Tissue
      culture plates containing monolayers of HUVEC were placed on a horizontal rotator
      (80 revolutions per minute (rpm)), and equal numbers of purified human
      eosinophils or neutrophils were added to separate wells at 4 degrees C. Binding
      of eosinophils and neutrophils to unstimulated endothelial cells was 15 +/- 3 and
      31 +/- 11 cells/four high power fields (HPF), respectively. After preincubation
      of HUVEC with IL-1 beta (1 ng/ml, 4 h, 37 degrees C), adhesion increased to 56 +/
      4 and 290 +/- 26 cells/four HPF, respectively (p < 0.0002 for both, n = 8-14).
      Eosinophils with reduced levels of L-selectin (blood eosinophils activated in
      vitro or eosinophils obtained from bronchoalveolar lavage (BAL) performed after
      segmental lung allergen challenge of allergic subjects) demonstrated reduced
      binding under rotating conditions. Several L-selectin Abs inhibited adhesion of
      eosinophils and neutrophils (e.g., LAM1-3: 43 +/- 14% vs 63 +/- 3% inhibition;
      LAM1-6: 73 +/- 5% vs 36 +/- 6% inhibition, respectively, n > or = 6).
      Interestingly, one additional L-selectin Ab, LAM1-11, inhibited eosinophil but
      not neutrophil adhesion (51 +/- 2% vs 1 +/- 7% inhibition, respectively, n > or =
      5). We conclude that eosinophils, like neutrophils, use L-selectin to bind to
      activated endothelial cells under conditions of flow, although mAb LAM1-11 can
      selectively inhibit eosinophil attachment to stimulated endothelial cells in
      vitro, suggesting different functional epitopes on L-selectin among eosinophils
      and neutrophils.

PMID- 7519644
TI  - Transforming growth factor-beta prevents stem cell factor-mediated rescue of mast
      cells from apoptosis after IL-3 deprivation.
AB  - IL-3-dependent mast cells undergo apoptosis upon removal of IL-3, an event that
      is prevented by the addition of stem cell factor (SCF) acting through its
      receptor c-kit, suggesting that SCF provides a mechanism to allow mast cells to
      survive and to differentiate in tissues in the relative absence of IL-3. This
      observation is consistent with the thesis that the microenvironment, in part,
      controls mast cell number and viability by modulating SCF production and release.
      The purpose of the present study was to determine whether a second factor, TGF
      beta 1, was capable of modifying the SCF-mediated survival pathway. TGF-beta 1 (1
      and 10 ng/ml), known to be an important regulator of cell growth and function,
      did inhibit the SCF-mediated rescue from apoptosis in IL-3-deprived mast cells.
      TGF-beta 1 exerted its inhibitory effect on SCF-mediated rescue from apoptosis,
      even when added 4 h after the addition of SCF. In contrast, TGF-beta 1 had no
      substantial effect on the viability of mast cells that were grown in the presence
      of IL-3. TGF-beta 1 also had no noticeable effect on viability and proliferation
      of a growth factor-independent mast cell line. The inhibitory effect of TGF-beta
      1 was neutralized by specific anti-TGF-beta mAb. TGF-beta 1 did not affect the
      expression of c-kit, as determined by using flow cytometric analysis of mast
      cells labeled with FITC-conjugated anti-c-kit. These results demonstrate how SCF
      and TGF-beta may act in concert to regulate mast cell numbers under physiologic
      or pathologic conditions.

PMID- 7519645
TI  - Ligand binding to monocyte alpha 5 beta 1 integrin activates the alpha 2 beta 1
      receptor via the alpha 5 subunit cytoplasmic domain and protein kinase C.
AB  - Regulation of the functional status of integrin receptors plays a critical role
      in inflammation and tissue remodeling, as it affects cell adherence and cytokine
      secretion. We have previously shown that in monocytes the binding of collagen to
      the alpha 2 beta 1 integrin induces the release of IL-1, an event that is
      potentiated by binding of fibronectin (Fn) to the alpha 5 beta 1 integrin. In
      this study, we have investigated the mechanisms leading to this phenomenon. Fn
      binding to alpha 5 beta 1 induced intracellular signals which increased the alpha
      2 beta 1-dependent adhesiveness of monocytes to collagen without modifications of
      alpha 2 beta 1 expression. By using Abs against the intracellular region of the
      alpha 5 subunit of the alpha 5 beta 1 receptor, and specific inhibitors of
      protein kinase C (PKC), we found that the potentiation effect of Fn on monocyte
      IL-1 production and their adherence to collagen was dependent on an intact alpha
      5 subunit cytoplasmic domain, and required PKC activation. Although the alpha 2
      beta 1 could be activated by several intracellular second messengers, including
      protein kinase A and intracellular calcium, the potentiating effect of Fn was
      mediated only by PKC. These data provide an example of a novel regulatory
      mechanism: potentiation of beta 1 integrin-mediated events as a result of ligand
      binding to another integrin of the same class. They also show that the
      intracellular region of alpha 5 beta 1 plays a critical role in transducing
      signals generated by ligand binding to alpha 5 beta 1.

PMID- 7519646
TI  - Inhibition of lipopolysaccharide and IL-1 but not of TNF-induced activation of
      human endothelial cells by suramin.
AB  - The binding and trans-endothelium migration of inflammatory cells is believed to
      play a critical role in a variety of inflammatory conditions. This study
      investigates the ability of the experimental drug suramin to block the activation
      of HUVEC by endotoxin and by the proinflammatory cytokines IL-1 and TNF. We
      demonstrate that the inducible expression of several adhesion molecules by LPS
      and IL-1 beta but not by TNF-alpha is prevented by suramin. In a dose-dependent
      manner, suramin inhibits the binding of neutrophils and T lymphocytes to LPS and
      IL-1 beta but not to TNF-alpha-activated HUVEC. The inhibitory effect of the drug
      on IL-1 beta-induced but not on LPS-induced cell stimulation can be completely
      reversed by the addition of excess cytokine but not by excess LPS. Because LPS
      activation of HUVEC is known to depend on serum/plasma-derived soluble CD14, we
      set out to determine whether suramin inhibition involves interference with the
      action of the CD14-LPS complex on HUVEC. Indeed, the drug prevents the binding of
      radioactive LPS in the presence of serum and inhibits LPS-induced cell activation
      in serum-free medium supplemented with recombinant soluble CD14. The results
      suggest that suramin interferes with the CD14-dependent activation of HUVEC and
      that it also may be a useful agent in blocking infectious endotheliopathies in
      vivo.

PMID- 7519648
TI  - A cross-reactive idiotope on T cells from PL/J mice and Lewis rats that
      recognizes different myelin basic protein encephalitogenic epitopes but is
      restricted by TCR V beta 8.2.
AB  - Encephalitogenic T cells of both PL/J mice and Lewis rats are restricted by TCR V
      beta 8.2, although they recognize different epitopes in the myelin basic protein
      (MBP) molecule. We sought the presence of a cross-reactive idiotope (Id) in
      encephalitogenic T cells of Lewis rats by examining the effects of mAb F30 anti
      Id, which recognized a TCR Id in PL/J T cells, on the encephalitogenic LR88L1
      cell line derived from Lewis rats and specific for guinea pig MBP peptide 68-88.
      The LR88L1 cells were I-A restricted and TCR V beta 8.2+, and their proliferation
      and secretion of IL-2 and TNF-alpha induced by guinea pig MBP peptide 68-88 was
      inhibited by mAb F30 anti-Id. As shown by FACS analysis and by
      immunoprecipitation of TCR from radiolabeled LR88L1 cell lysates, the F30 anti-Id
      bound to the TCRs of V beta 8.2+ LR88L1 cells. In addition, TCR sequences in the
      F30+ population of LR88L1 cells were the same as those of encephalitogenic Lewis
      rat T cells published previously. The F30+ LR88L1 cells showed reduced
      encephalitogenicity compared with F30- or unsorted LR88L1 cells. The mechanism
      for this reduction by anti-Id probably resulted from the induction of anergy, in
      that IL-2 reversed the anti-Id effect. The control LR99L1 T cell line, also
      encephalitogenic, but specific for MBP peptide 87-99 and I-E, and not TCR V beta
      8.2 restricted, failed to react with, or have its cytokine secretion inhibited
      by, mAb F30 anti-Id. These results demonstrate an interspecies cross-reactive Id
      expressed in common by encephalitogenic T cells that share a similar TCR,
      although they differ in MBP epitope specificity. These findings suggest that a
      common Id restricted by TCR, but less restricted by the encephalitogenic epitope,
      and recognized by the Id-bearing autoreactive T cells may represent an
      immunotherapeutic approach for treating autoimmune demyelinating diseases.

PMID- 7519649
TI  - Elimination kinetics of prostate-specific antigen serum and urine.
AB  - The serum half-life of prostate-specific antigen (PSA) was calculated in 66
      patients subsequent to radical prostatectomy. Comparing serum half-life to
      disease outcome in 37 patients after a minimum follow-up of two years, it was
      found that PSA serum half-life identifies patients with residual disease earlier
      and more reliably than the presence or absence of detectable PSA levels
      postoperatively. It is suggested that residual tumor affects the half-life by
      contributing to the serum level of PSA. When PSA serum half-life was calculated
      solely in potentially cured patients, we found a half-life of 1.6 days, which is
      considerably shorter than in previous reports based on patient populations
      regardless of the outcome of disease in the follow-up. To elucidate the route of
      PSA elimination, serial urine PSA levels were determined before and after radical
      prostatectomy, revealing strong evidence for the assumption that PSA is not
      eliminated by the kidneys in its unchanged form.

PMID- 7519647
TI  - Autoantibodies to human nuclear lamin B2 protein. Epitope specificity in
      different autoimmune diseases.
AB  - The nuclear lamina of mammalian cells consists of three major proteins, lamins A,
      C, and B, and a fourth minor protein, lamin B2. Lamins belong to the family of
      intermediate filaments and are highly similar both in structure and primary
      sequence. They are organized in three well-defined domains: 1) a central alpha
      helical rod, which is a secondary structure shared by all types of intermediate
      filaments, formed by three alpha-helices (coils 1A, 1B, and 2) and surrounded by
      2) an amino-terminal head and 3) a carboxyl-terminal tail. Autoantibodies toward
      major lamin have been described previously in sera from patients with different
      autoimmune diseases. We chose an epitope mapping approach to further characterize
      the autoimmune response to nuclear lamin. Different lamin B2 domains were
      expressed as fusion proteins with the glutathione S-transferase and then used in
      immunoblotting experiments to analyze sera from patients with autoimmune diseases
      (chronic active hepatitis, SLE, rheumatoid arthritis, and polymyalgia rheumatica)
      and from healthy subjects. At a 1:1000 dilution, none of the control sera
      recognized any of the recombinant polypeptides. Conversely, reactive sera were
      present in all groups of patients. The ability to recognize a protein domain
      seemed to differ with the pathology. Most chronic active hepatitis sera were
      reactive to two or more lamin domains and reacting SLE sera always gave positive
      signals to coil 2 and/or coil 1B. Coil 2 was preferentially recognized by
      rheumatoid arthritis sera. Polymyalgia rheumatica sera differed from all of the
      others because of their low reactivity to the rod domain and preference for the C
      terminus, a lamin-specific domain.

PMID- 7519650
TI  - Serum tumor marker half-life during chemotherapy in patients with germ cell
      tumors.
AB  - Approximately 80% of previously untreated men with metastatic germ cell tumors
      will be cured with cisplatin-based chemotherapy. Serum levels of alpha
      fetoprotein (AFP) or human chorionic gonadotropin (HCG) or both are increased in
      most of these patients. Pre-treatment clinical characteristics can be used to
      distinguish between "good" and "poor" risk patients who are either highly likely
      or unlikely to achieve a complete remission, respectively. A slow rate of decline
      of either AFP or HCG or both has been associated with an inferior survival in
      both good and poor risk patients. In multivariate analysis, the pre-treatment
      risk status and the post-treatment clearance of markers were independent and
      equal prognostic variables. Similarly, in patients receiving cisplatin+ifosfamide
      based salvage chemotherapy, the rate of decline of HCG was an independent
      predictor variable in addition to the primary site and pre-treatment HCG levels
      for both overall and event-free survival. Prolonged half-life clearance of serum
      tumor markers is an important prognostic variable in both previously untreated as
      well as previously treated germ cel tumor patients. Treatment strategies can be
      based on marker clearance and prospective clinical trials are warranted.

PMID- 7519651
TI  - AFP and HCG in germ cell tumors.
AB  - The high specificity and sensitivity of testicular tumor markers make them
      particularly useful in the management of these neoplasms. Basal value represents
      an independent prognostic variable, influencing the choice of therapy. An
      increase in marker level before chemotherapy could also acquire a powerful
      prognostic significance. The decay curve pattern is indicative of the radicality
      of surgery. Also during chemotherapy the behavior of markers conditions further
      therapeutic strategies.

PMID- 7519653
TI  - In vitro and in vivo regulation of human tumor antigen expression by human
      recombinant interferons: a review.
AB  - The ongoing development of monoclonal antibody technology may eventually lead to
      the selective targeting of human carcinoma lesions by MAbs conjugated with a
      variety of cytotoxic agents (i.e., radionuclides, drugs, etc.). The antigen
      phenotype of the carcinoma cell will play an important role in the efficacy of
      the MAbs. Clearly, the human tumor antigens that are expressed on all carcinoma
      cells, and with a high antigen density, should provide the optimal target for the
      MAbs. More often than not, however, the human tumor antigens whose expression is
      highly selective for human tumor cells will also exhibit a certain degree of
      heterogeneity. Therefore, the ability of interferon to augment the level of
      expression of human tumor antigens such as TAG-72 and CEA, may play an important
      role in an adjuvant setting for immunoscintigraphy and/or immunotherapy. More
      recent observations have demonstrated that interferon treatment can also enhance
      the amount of TAG-72 and CEA secreted by the tumor cell. The ability of
      interferon to enhance the shedding of both TAG-72 and CEA could be of particular
      importance since recent reports suggest that their presence in the sera of
      patients diagnosed with gastrointestinal adenocarcinoma may be complementary and
      that the ability to increase either marker may facilitate earlier diagnosis of
      recurrent disease. It is conceivable that in subsequent years effective
      approaches to monitoring and/or treating malignancies may include a new
      combination of biological/immunological therapy.

PMID- 7519652
TI  - Marker determination for response monitoring: radiotherapy and disappearance
      curves.
AB  - This paper reports the results of studies on the possible role of biochemical
      markers in monitoring the effects of ionizing radiations and in the follow-up of
      cancer patients submitted to radiotherapy. Three different case series were
      analyzed: patients with head and neck cancer, prostate carcinoma and residual
      thyroid tumors or uptaking metastases (131-Iodine therapy). Serum TPA and amylase
      were serially determined in patients with head and neck or thyroid cancer to
      measure the radiation damage to the salivary glands. In the former group a
      statistically significant correlation between the increase of both molecules and
      the total dose administered after the first day of treatment (2, 3, 4 or 6 Gy)
      was observed. In patients treated for thyroid cancer the damage to the salivary
      glands was revealed by an increase in TPA and amylase serum levels, dependent on
      the dose of 131-Iodine administered. Moreover, an association was demonstrated
      between pretreatment values of TPA in patients with head and neck tumors and
      prognosis: patients with values below the cutoff have significantly higher
      survival rates than those with higher values. In patients with prostate carcinoma
      PSA was confirmed to have better diagnostic and prognostic value than PAP.
      Patients with metastases show an inversion or lack of negative trend in PSA
      levels observed in the disease-free patients. This precedes the clinical
      diagnosis of metastases by 1 to 15 months.

PMID- 7519654
TI  - Insulin-like growth factors (IGF-I and IGF-II), IGF-binding proteins, and IGF
      gene expression in the offspring of ethanol-fed rats.
AB  - Insulin-like growth factors I and II (IGF-I, IGF-II) and IGF-binding proteins
      (IGBPs) are important modulators of fetal growth. Fetal growth retardation is a
      major component of the fetal alcohol syndrome, which is associated with maternal
      alcoholism. This study examined the relationship of IGF-system components to
      growth retardation induced by ethanol in fetuses of rats fed equicaloric liquid
      diets (AF, ad libitum-fed controls; PF, pair-fed controls; EF, ethanol-fed)
      during gestation. The gene expression of IGF-I and IGF-II in fetal liver and the
      concentration of IGFs and IGFBPs in serum and liver were determined. The mean
      weight of EF fetuses was 13% and 16% less (p < 0.01) than that of PF and AF
      offspring, respectively. The serum concentration of IGF-I was decreased (p <
      0.05) by 17% and 22% in EF as compared with PF and AF fetuses. Fetal body weight
      showed positive correlations with fetal serum IGF-I IGF-II (r = 0.566, p < 0.01,
      and r = 0.412, p < 0.05, respectively) Fetal liver weight correlated with fetal
      liver IGF-I and IGF-II, with r values of 0.514 (p < 0.01) and 0.493 (p < 0.01).
      Hepatic IGF-II mRNA abundance was decreased (p < 0.05) by 27% and 26% in EF as
      compared with PF and AF offspring. The level of fetal liver IGF-I mRNA expression
      was low but was also reduced comparably in EF pups. IGFBP content in EF fetal
      serum was increased (p < 0.05 vs AF), and correlated negatively with fetal body
      weight (r = -0.505, p < 0.01). The diminished IGF-I and IGF-II gene expression
      and the reduced tissue and circulating peptide levels, along with a converse
      change in serum IGFBP abundance, may have a role in the pathogenesis of fetal
      alcohol syndrome.

PMID- 7519655
TI  - Exposure to lead and specific attentional problems in schoolchildren.
AB  - A pilot study was carried out to investigate the relationship between exposure to
      lead and attention in children. The participants were 43 boys, 8 to 12 years of
      age, attending special schools for children with educational and/or learning
      problems (so called LOM schools). Children with probable causes of attentional or
      memory problems other than lead contamination were excluded from the study.
      Various aspects of attention were measured using neuropsychological tests. As an
      assessment of body lead burden, lead concentration in the boys' hair was measured
      by means of the Synchrotron Radiation-Induced X-ray Fluorescence technique
      (SXRF). Information was collected about variables that possibly could influence
      attention and/or body lead burden (confounding factors). A multiple regression
      analysis was used to determine the contribution of lead to variance in
      performance, after correction for confounding factors. The results showed that
      children with relatively high concentrations of lead in their hair reacted
      significantly slower in a simple reaction-time task than did children with
      relatively low concentrations of lead in their hair. In addition, the former were
      significantly less flexible in changing their focus of attention, even after
      correction for the influence of their delayed reaction time.

PMID- 7519656
TI  - Time-course of inhibition of cellular nucleic acid synthesis by selenite.
AB  - The relationship between intracellular sulfhydryl(SH) compounds and the kinetics
      of the inhibitory effect of selenite on cellular nucleic acid synthesis has been
      examined. In A549 cells, with a relatively high SH level, exposure to low
      concentrations of selenite caused inhibition even after short exposure times. In
      contrast, in VA cells, with a relatively low level of SH compounds, selenite had
      no significant effect at short exposure times, but inhibited significantly with
      longer exposures. Selenodicysteine, the product of the reaction of selenite with
      cysteine (an important intracellular SH compound), inhibited synthesis in both
      cell types at short exposure times. Exposure of cells to diethylmaleate, which
      decreased the level of intracellular SH compounds, reduced the inhibitory effect
      of a short exposure to selenite but did not affect a long exposure. These results
      indicate that the reaction of selenite with intracellular SH compounds may be a
      determining factor in the kinetics of its inhibitory effect on cellular DNA and
      RNA synthesis.

PMID- 7519658
TI  - In vitro hypoxia induces expression of the NR2C subunit of the NMDA receptor in
      rat cortex and hippocampus.
AB  - In mammalian brain, ischemic injury could be mediated by delayed glutamate
      neurotoxicity. We have studied the possibility of altered genetic expression of
      quiescent NMDA receptor subunits in an in vitro model of hypoxia-hypoglycemia,
      using the reverse transcription-polymerase chain reaction technique. It was found
      that mRNA corresponding to the NR2C subunit was present 1 h after a brief hypoxic
      hypoglycemic episode in adult rat hippocampus and cortex but absent in control
      tissue. These findings indicate that the phenotypic characteristics of certain
      brain cells after an ischemic insult are altered by the expression of genes that
      are quiescent in those cells under normal physiological conditions.

PMID- 7519657
TI  - Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical
      and behavioral deficits associated with partial nigrostriatal dopamine lesions.
AB  - Brain-derived neurotrophic factor (BDNF) promotes the survival of dopamine (DA)
      neurons, enhances expression of DA neuron characteristics, and protects these
      cells from 6-hydroxydopamine (6-OHDA) toxicity in vitro. We tested the ability of
      BDNF or neurotrophin-3 (NT-3) to exert similar protective effects in vivo during
      chronic delivery of 6-OHDA to the rat neostriatum. Chronic infusions of BDNF or
      NT-3 (12 micrograms/day) above the substantia nigra were started 6 days before
      and continued during an 8-day chronic intrastrial infusion of 6-OHDA. In control
      and neurotrophin-treated animals, 6-OHDA treatment selectively depleted 50-60% of
      nigrostriatal DA nerve terminals but produced little if any loss of pars compacta
      DA cell bodies. This partial DA lesion resulted in three rotations per minute
      toward the lesioned hemisphere after treatment with the DA release-inducing drug
      d-amphetamine. Compared with supranigral infusions of vehicle, BDNF and NT-3
      decreased the number of these ipsiversive rotations by 70 and 48% and increased
      by 20- and 10-fold, respectively, the number of contraversive rotations observed
      after amphetamine injection. When challenged with the DA receptor agonist
      apomorphine, BDNF- and NT-3-treated animals also exhibited a seven- and 3.5-fold
      increase in the number of contraversive rotations relative to the vehicle group,
      respectively. Compared with vehicle, BDNF increased striatal levels of
      homovanillic acid (HVA; 86%), 3,4-dihydroxyphenylacetic acid (DOPAC; 42%), and 5
      hydroxyindoleacetic acid (5-HIAA; 32%) and the HVA/DA (43%) and 5-HIAA/serotonin
      (34%) ratios in the DA-denervated striatum. NT-3 augmented only striatal 5-HIAA
      levels (24%). Neither factor altered the 6-OHDA-induced decrease in striatal DA
      levels or high-affinity DA uptake and thus did not protect against the
      destruction of DA terminals and did not alter striatal D1 or D2 ligand binding.
      Choline, GABA, and glutamate uptake in the striatum were not altered by the
      lesion or neurotrophin treatment. Thus, BDNF and to a lesser extent NT-3 reverse
      rotational behavioral deficits and augment striatal DA and 5-HT metabolism in a
      partial DA lesion model.

PMID- 7519660
TI  - m1-m5 muscarinic receptor distribution in rat CNS by RT-PCR and HPLC.
AB  - Five muscarinic receptor genes (m1-m5) that encode distinct muscarinic receptor
      subtypes have been cloned. Because of their structural homology and
      pharmacological similarity, ligand binding probes currently available do not
      clearly distinguish among the subtypes. To obtain a clear distribution within the
      CNS of molecularly defined muscarinic receptor subtypes, seven brain regions were
      examined for the expression of the respective mRNAs. The most sensitive method
      for detecting mRNA is through amplification of the respective cDNAs. Brain
      regions were obtained from male Wistar rats, and total RNA was isolated. The
      isolates were extensively treated with RNase-free DNase to remove any residual
      genomic DNA. Total RNA (1 microgram) was reverse-transcribed using random primers
      and reverse transcriptase. The resulting cDNA was amplified using a thermal
      cycler, and the polymerase chain reaction (PCR)-amplified products were analyzed
      by gel electrophoresis containing ethidium bromide and visualized with
      fluorescent illumination. PCR-amplified samples were also injected directly onto
      an HPLC anion exchange column and quantified by UV detection. Each of the five
      muscarinic subtypes was found in every brain region examined. The m1 subtype was
      most abundant in cortex and gradually declined in content caudally to the spinal
      cord. The m2 subtype was most abundant in thalamus-hypothalamus and ponsmedulla.
      The m4 subtype was found in greatest amount in the striatum, whereas m3 and m5
      were expressed consistently throughout the CNS. The combination of RT-PCR and
      HPLC provides a rapid and sensitive method for quantifying the expression of mRNA
      coding for all five muscarinic receptor subtypes derived from the CNS.

PMID- 7519662
TI  - A new look at the promoter of the human monoamine oxidase A gene: mapping
      transcription initiation sites and capacity to drive luciferase expression.
AB  - Monoamine oxidase (MAO) A (EC 1.4.3.4) oxidizes norepinephrine and serotonin and
      is expressed in a cell type-specific manner. Recent evidence that MAO A-deficient
      males in a large Dutch kindred suffer from mild mental retardation and occasional
      episodes of impulsive aggressive behavior makes it important to understand how
      the human MAO A promoter is regulated. Conventional primer extension analyses of
      MAO A mRNA in earlier studies predicted incorrect transcription initiation sites
      for the human MAO A promoter. Reverse transcription and polymerase chain reaction
      (PCR) readily detected MAO A mRNA initiated 5' to -135 bp but not 5' to -226 bp
      (5' to the ATG initiation codon). PCR-assisted primer extension and RNase
      protection assays reveal that most MAO A mRNA is initiated between -30 and -40,
      which resembles a eukaryotic initiator element. Depending on the tissue source, a
      minor, variable proportion of MAO A mRNAs is initiated more distally at
      approximately -95 and -136, within the more proximal of two 90-bp GC-rich tandem
      repeats. Genomic DNA segments spanning -4 to -200 and -465 or -935, but not -4 to
      -82, drive robust luciferase expression in mammalian cells. We conclude that (a)
      the primary transcription initiation site occurs at a putative initiator (lnr)
      element located between -30 and -40, with a minor, tissue-specific proportion of
      additional initiation near -95 and -136; and (b) MAO A-luciferase reporter
      constructs that contained all the known transcription initiation sites exhibited
      no evidence for inhibitory cis elements between -200 and at least -935. The
      apparent inhibitory activity previously reported for sequences 5' to the most
      proximal PvuII site may have resulted from the use of partial promoter constructs
      that omitted the putative lnr element.

PMID- 7519661
TI  - A combination of PLP and DM20 transgenes promotes partial myelination in the
      jimpy mouse.
AB  - Mutations in the myelin proteolipid protein (PLP) gene, such as that found in the
      jimpy mouse, result in an abnormal structure of the myelin, severe
      dysmyelination, and a reduction in the number of mature oligodendrocytes. To
      examine the functions of the two alternatively spliced isoforms of proteolipid
      protein, transgenic mice were generated that express either PLP or DM20 cDNAs
      placed under control of the PLP upstream regulatory region. The transgenes were
      bred into jimpy mice, and the effect of the transgenes on the dysmyelinating
      phenotype was analyzed. Neither the PLP transgene nor the DM20 transgene alone
      had an effect on myelination in the jimpy mice. Combining the two transgenes
      substantially increased the number of myelinated axons, suggesting that the two
      alternatively spliced products of the PLP locus perform distinct functions in
      oligodendrocytes. The enhanced myelination was not sufficient, however, for
      completely correcting the dysmyelinating phenotype of the jimpy mice, nor was it
      accompanied by the restoration of normal levels of myelin gene expression. The
      inability to rescue the jimpy phenotype is most likely attributable to a dominant
      negative action of the abnormal proteolipid proteins present in jimpy mice. These
      results demonstrate the complexity of proteolipid protein function in
      myelination.

PMID- 7519663
TI  - Evidence that protein kinase C activities involved in regulating neurite growth
      are localized to distal neurites.
AB  - Previously, we observed that long-term treatment of distal nerve fibers of rat
      sympathetic neurons in compartmented cultures with phorbol 12-myristate 13
      acetate (PMA) caused a reduction in the rate of neurite elongation by > 50%. In
      the present report we show that protein kinase C (PKC) activity could be measured
      in extracts of distal neurites by an assay of the Ca(2+)-dependent
      phosphorylation of a PKC-specific octapeptide substrate. We found that local
      application of 1 microM PMA for 24 h to distal neurites caused nearly complete
      down-regulation of Ca(2+)-dependent PKC activity measured in this manner. We
      determined that the inhibition of neurite elongation by PMA was mediated by local
      mechanisms in the neurites because local application of PMA to center
      compartments containing cell bodies and proximal neurites did not inhibit the
      rate of elongation of distal neurites. We then investigated the effects of the
      recently available PKC inhibitors, calphostin C and chelerythrine, finding that,
      like PMA, these inhibited the growth of distal neurites when applied locally to
      them, and had no effect when applied to cell bodies and proximal neurites.
      However, the inhibition of neurite growth by calphostin C occurred at a
      concentration far below its IC50 value for protein kinase inhibition, and both
      calphostin C and chelerythrine inhibited distal neurite growth even in neurons
      pretreated with PMA. Thus, it appears that these agents do not all inhibit
      neurite growth through the same mechanisms. Although the PKC activities involved
      in neurite elongation in sympathetic neurons have not been precisely defined,
      these data presented in this study indicate that protein kinases localized to
      growth cones play a complex and important role in regulating axonal growth.

PMID- 7519659
TI  - Altered brain metabolism of iron as a cause of neurodegenerative diseases?
AB  - Iron is the most abundant metal in the human body (Pollitt and Leibel, 1982;
      Youdim, 1988), and the brain, like the liver, contains a substantially higher
      concentration of iron than of any other metal (Yehuda and Youdim, 1988). Within
      the brain, iron shows an uneven distribution, with high levels in the basal
      ganglia (substantia nigra, putamen, caudate nucleus, and globus pallidus), red
      nucleus, and dentate nucleus (Spatz, 1922; Hallgren and Sourander, 1958; Hill and
      Switzer, 1984; Riederer et al., 1989). Iron deposition in the brain is mainly in
      organic storage forms such as ferritin but not hemosiderin (Hallgren and
      Sourander, 1958; Octave et al., 1983), with relatively little in a free and
      reactive form. Although the function of a regionally high brain iron content is
      unknown, the homeostasis of brain iron is thought to be necessary for normal
      brain function, especially in learning and memory (Youdim et al., 1989; Yehuda
      and Youdim, 1989; Pollit and Metallinos-Katsaras, 1990; Youdim, 1990). Thus, a
      high content of brain iron may be essential, particularly during development, but
      its presence means that injury to brain cells may release iron ions that can lead
      to oxidative stress via formation of oxygen free radicals. Such radicals are
      thought to be involved in lipid peroxidation of the cell membrane, leading to
      increased membrane fluidity, disturbance of calcium homeostasis, and finally cell
      death (Youdim et al., 1989; Halliwell, 1992). Iron is an essential participant in
      many metabolic processes, including (a) DNA, RNA, and protein synthesis, (b) as a
      cofactor of many heme and nonheme enzymes, (c) the formation of myelin, and (d)
      the development of the neuronal dendritic tree (Ben-Shachar et al., 1986; Youdim
      et al., 1991b). A deficiency of iron metabolism would therefore be expected to
      alter some or all of these processes (Jacobs and Worwood, 1980; Youdim, 1985,
      1988). Studies of iron distribution in the human brain have demonstrated that the
      degree of iron deposition, primarily in the basal ganglia (a predominantly
      dopamine structure), increases with age (Hallgren and Sourander, 1958) and in
      certain disorders, most notably the basal ganglia disorders (Seitelberger, 1964).
      This review will present some of the experimental evidence indicating a role of
      disturbed iron metabolism as a cause of the neurodegenerative disorder
      Parkinson's disease and possibly other neurodegenerative disorders such as
      Alzheimer's disease.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7519664
TI  - Plasminogen activator inhibitor-1 expression by brain microvessel endothelial
      cells is inhibited by elevated glucose.
AB  - Patients with diabetes are predisposed to microvascular disease. In the retina
      and brain, this is characterized by neovascularization and new capillary
      formation. Because of the potential importance of plasmin generation in these
      processes, we evaluated the effect of elevated glucose concentrations on
      expression of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen
      activator (tPA), and urokinase (uPA) in cultured bovine brain endothelial cells
      (BBEC) versus cultured bovine aortic endothelial cells (BAEC). We observed that
      BBEC PAI-1 mRNA levels were decreased fivefold in cells cultured in media
      containing 20 mM glucose compared with BBEC cultured in media with 5.5 mM
      glucose, whereas expression of PAI-1 mRNA in BAEC, bovine mesenteric endothelial
      cells, and human umbilical vein endothelial cells was not modulated under these
      conditions. Expression of PAI-1 protein was also inhibited by growth of BBEC in
      elevated glucose, but the effect was less marked than at the mRNA level. Elevated
      glucose did not decrease expression of PAI-1 protein by BAEC. Withdrawal of
      acidic fibroblast growth factor enhanced expression of PAI-1 mRNA and protein in
      BBEC. Expression of tPA mRNA was not affected by the glucose concentration of the
      medium, and uPA mRNA was not detected in our BBEC cultures. A decrease in the
      local tissue activity of PAI-1 by elevated glucose concentrations, with no effect
      on tPA or uPA expression, would lead to an increase in the plasmin activity and
      thereby predispose neural tissues, such as the cerebrum and retina, of diabetic
      patients to neovascularization.

PMID- 7519665
TI  - Nitric oxide-mediated inhibition of the mitochondrial respiratory chain in
      cultured astrocytes.
AB  - The Ca(2+)-independent form of nitric oxide synthase was induced in rat neonatal
      astrocytes in primary culture by incubation with lipopolysaccharide (1
      microgram/ml) plus interferon-gamma (100 U/ml), and the activities of the
      mitochondrial respiratory chain components were assessed. Incubation for 18 h
      produced 25% inhibition of cytochrome c oxidase activity. NADH-ubiquinone-1
      reductase (complex I) and succinate-cytochrome c reductase (complex II-III)
      activities were not affected. Prolonged incubation for 36 h gave rise to a 56%
      reduction of cytochrome c oxidase activity and a 35% reduction in succinate
      cytochrome c reductase activity, but NADH-ubiquinone-1 reductase activity was
      unchanged. Citrate synthase activity was not affected by any of these conditions.
      The inhibition of the activities of these mitochondrial respiratory chain
      complexes was prevented by incubation in the presence of the specific nitric
      oxide synthase inhibitor NG-monomethyl-L-arginine. The
      lipopolysaccharide/interferon-gamma treatment of the astrocytes produced an
      increase in glycolysis and lactate formation. These results suggest that
      inhibition of the mitochondrial respiratory chain after induction of astrocytic
      nitric oxide synthase may represent a mechanism for nitric oxide-mediated
      neurotoxicity.

PMID- 7519666
TI  - Modulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      binding sites by nitric oxide.
AB  - Nitric oxide release is reported to be involved in physiological processes
      associated with altered sensitivity of the alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) class of glutamate receptor. A series of
      compounds liberating nitric oxide were therefore tested for their ability to
      modulate in vitro the characteristics of [3H]AMPA binding to sections of rat
      brain. Pretreatment of forebrain or cerebellar sections with sodium nitroprusside
      (1 mM), S-nitroso-N-acetylpenicillamine (SNAP, 200 microM), glyceryl trinitrate
      (1 microM), or isosorbide dinitrate (0.5 mM) all increased the binding of 3 nM
      [3H]AMPA by 15-30%. These actions were reproduced by 8-bromo-cyclic GMP (200
      microM) in the cerebellum but not in the forebrain. In a similar manner, the
      effect of SNAP was attenuated by an inhibitor of cyclic GMP-dependent protein
      kinase in the cerebellum but not in the forebrain. The elevated [3H]AMPA binding
      observed after pretreatment with SNAP was caused by an increase in binding
      affinity, but the capacity of the sites was unchanged. Autoradiographic analysis
      showed that forebrain binding was enhanced in the cerebral cortex and hippocampus
      but not in the striatum. Nitric oxide therefore appears to be able to increase
      the affinity of AMPA binding sites via two distinct mechanisms in different brain
      areas. This action may contribute to synaptic plasticity associated with nitric
      oxide release.

PMID- 7519667
TI  - Corticosterone regulates heme oxygenase-2 and NO synthase transcription and
      protein expression in rat brain.
AB  - Heme oxygenase (HO)-1 and -2 produce carbon monoxide, which is suspected, as is
      nitric oxide (NO), to function as a neuronal messenger. We report on
      glucocorticoid-mediated modulation of HO-2 and NO synthase expression in brain
      and the differential response of the two proteins to corticosterone in different
      brain regions. Corticosterone treatment (40 mg/kg, 20 days) had opposing effects
      on HO-2 and NO synthase transcript levels: increasing the 1.3- and 1.9-kb HO-2
      mRNAs and decreasing that of the brain-specific 10.5-kb NO synthase.
      Corticosterone did not uniformly affect HO-2 protein expression in all regions,
      but appeared to cause a universal reduction in NO synthase, e.g., HO-2 was
      decreased in hippocampus (CA1 and dentate gyrus), but not in cerebellum. In
      contrast, NADPH diaphorase staining was reduced in hippocampus and in molecular
      and granule layers of cerebellum (not detected in Purkinje cells). Striking
      deficits in neuronal morphology and number of diaphorase-staining neurons were
      observed in the lateral tegmental area, paraventricular nucleus, and frontal
      cortex; HO-2 expression was only selectively affected. In cerebellum, activity of
      NO synthase, but not that of HO, was reduced. Consistent with the possibility
      that carbon monoxide can generate cyclic GMP, the change in cyclic GMP level did
      not mirror the decrease in NO synthase. We suggest that glucocorticoid-mediated
      deficits in hippocampal functions may reflect their negative effect on messenger
      generating systems.

PMID- 7519668
TI  - Regulation of the release of interleukin-6 from human astrocytoma cells.
AB  - Recent evidence suggests that the level of interleukin-6 (IL-6) is elevated in
      Alzheimer's disease (AD) brains. IL-6 is produced by reactive glial cells and
      could potentially affect neuronal survival. Understanding the biochemical
      mechanism that regulates the production and release of IL-6 by astrocytic cells
      may help to identify potential targets for therapeutic intervention in AD. In the
      present study, glial fibrillary acidic protein-positive human U373MG astrocytoma
      cells were used as a model of reactive astrocytes. Production of IL-6 in response
      to drug treatment was monitored with an ELISA assay. Histamine (1-100 microM),
      substance P (SP; 1-100 nM), and human interleukin-1 beta (IL-1 beta; 1-30 pM)
      stimulated the release of IL-6 in a time- and concentration-dependent manner,
      with EC50 values of 4.5 microM, 8 nM, and 4.5 pM, respectively. The respective
      effects of histamine, SP, and IL-1 beta were effectively blocked by the histamine
      H1, SP, and IL-1 receptor antagonists, supporting a receptor-mediated event for
      these agents. Both histamine and SP enhanced the formation of inositol phosphates
      and increase intracellular calcium levels, suggesting that the
      phosphatidylinositol bisphosphate/protein kinase C pathway may be involved in the
      IL-6 release process. Indeed, phorbol 12-myristate 13-acetate, a protein kinase C
      activator, also evoked IL-6 release from the U373MG cells. On the other hand, IL
      1 beta, which produces a much more robust release of IL-6 than histamine or SP,
      has no effect on inositol phosphate formation or intracellular calcium
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519670
TI  - A rapid anterograde axonal transport of carboxypeptidase H in rat sciatic nerves.
AB  - Using the highly sensitive HPLC-fluorophotometry technique, anterograde and
      retrograde axonal transport of carboxypeptidase H (CPH), a putative prohormone
      processing enzyme that removes a basic amino acid from the C-terminus of a
      precursor peptide, was measured 12-72 h after double ligations of rat sciatic
      nerves. CPH-like activity in rat sciatic nerves was 60-fold lower than that in
      the pituitary gland. CPH-like enzyme activity was rapidly accumulated in the
      proximal segment and peaked 48 h after ligation. The axonal flow was 100 mm/day,
      indicating that CPH in rat sciatic nerves is rapidly transported to the nerve
      terminals as an active form. The properties of the enzyme were similar to those
      of CPH in the brain: The pH optimum is at 5.5, and the molecular mass is
      approximately 5 kDa. These results suggest that active CPH in the PNS is
      transported by a rapid anterograde axonal flow and may play a role in converting
      proneuropeptides to active neuropeptides under the axonal transport.

PMID- 7519671
TI  - Binding sites of fluorescent probes on human serum albumin.
AB  - Human serum albumin is known to have two major and selective drug binding sites,
      termed sites I and II. The fluorescent probes, dansylamide and dansylsarcosine
      selectively interact with sites I and II, respectively. However, the binding site
      of the fluorescent probe dansylglycine on human serum albumin is not clear from
      the literature. This study investigated whether dansylglycine interacts tightly
      with site I or II. Spectrofluorimetric titrations (quenching and complex) and
      circular dichroism measurements were performed to determine the binding
      characteristics of dansylglycine to human serum albumin. Modification in probe
      fluorescence was described by fluorescence titrations to be a result of
      competitive displacement by ligands. The pattern of displacement of this probe by
      several ligands whose primary binding sites are exactly known, enabled the
      identification of its specific binding site. The fluorescence of dansylglycine is
      only extensively changed when ligands of site II are added, suggesting that it
      strongly interacts with the benzodiazepine/indole binding site on human serum
      albumin.

PMID- 7519669
TI  - Possible role of nitric oxide in catecholamine secretion by chromaffin cells in
      the presence and absence of cultured endothelial cells.
AB  - We studied the effect of cultured endothelial cells on the secretion of
      catecholamines by cultured bovine chromaffin cells. Chromaffin cell catecholamine
      secretion was stimulated by either boluses of potassium (K+) or the nicotinic
      agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP). Endothelial cells inhibited the
      catecholamine release and stimulatory effects of K+ and DMPP. This inhibition
      increased with time, and in 25 min the initial stimulated secretory response
      (100%) to 30 mM K+ or 25 microM DMPP dropped to 45 +/- 3% and 53.5 +/- 2.3%,
      respectively. This endothelial cells-induced inhibition was blocked by the nitric
      oxide synthase inhibitors N-nitro-L-arginine methyl ester (L-NAME) and N
      monoethyl-L-arginine (L-NMMA), and by the guanylate cyclase inhibitor methylene
      blue, indicating that the L-arginine/nitric oxide/cyclic GMP pathway is involved
      in this endothelial cell-chromaffin cell interaction. In the absence of
      endothelial cells, incubation of chromaffin cells with L-NAME, L-NMMA, or
      methylene blue also augmented the secretagogue-induced catecholamine secretion,
      indicating that nitric oxide from chromaffin cells could be implicated in an
      autoinhibitory process of catecholamine release. These results provide indirect
      evidence for the presence of nitric oxide synthase in bovine adrenomedullary
      chromaffin cells. Our results show that there is an autoinhibitory mechanism of
      catecholamine release in chromaffin cells and that an additional level of
      inhibition is observed when cultured vascular endothelial cells are present.
      These two inhibitory processes may have different origins, but they appear to
      converge into a common pathway, the L-arginine/nitric oxide synthase/guanylate
      cyclase pathway.

PMID- 7519672
TI  - Comprehensive T-cell epitope mapping of HIV-1 env antigens reveals many areas
      recognized by HIV-1-seropositive and by low-risk HIV-1-seronegative individuals.
AB  - Peripheral blood mononuclear cells from 12 asymptomatic human immunodeficiency
      virus (HIV)-1-seropositive and nine HIV-1-seronegative donors were screened for
      proliferative T-lymphocyte responses to peptides derived from a consensus
      sequence of the HIV-1 env gene products from 25 HIV-1 isolates. Two hundred
      seventy-eight overlapping 17mer peptides, incremented by three residues each,
      were pooled into groups, each containing eight sequential peptides, for use in
      proliferation tests. Thirty-eight additional peptides containing variant amino
      acid residues also were tested. Proliferation data were analyzed using an
      algorithm that reduced subjective bias and estimated the responding cell
      frequencies. Peripheral blood mononuclear cells from a majority of donors,
      regardless of HIV-1 status, recognized peptides within two pools derived from the
      gp120 sequence and peptides from one pool in gp41. Pool 25 peptides from gp41
      (centered around residue 600 of the gp160 consensus sequence) were recognized
      most frequently. The observed inability to differentiate between responses of HIV
      1-seropositive and HIV-1-seronegative individuals implies either a lack of HIV-1
      disease-related immunodominant env epitopes or functional abrogation of HIV-1 env
      specific T-helper lymphocyte responses soon after infection. The observed
      proliferation of T lymphocytes from noninfected, low-risk individuals questions
      the origin of the responses to HIV-1 env-derived peptides and suggest that
      preexisting, cross-reactive immunity could influence responses to HIV-1.

PMID- 7519674
TI  - Safety profile of didanosine among patients with advanced HIV disease who are
      intolerant to or deteriorate despite zidovudine therapy: results of the Canadian
      Open ddI Treatment Program.
AB  - The aim of this study was to ascertain the safety profile of didanosine (Videx;
      ddI) within the Canadian Open Treatment Program. Symptomatic HIV+ subjects with
      AIDS or ARC or CD4 < 200/mm3 were eligible to receive didanosine if they were
      either (a) intolerant to zidovudine (Retrovir, ZDV) or (b) deteriorating despite
      ZDV therapy. The dose of didanosine (powder formulation) was based on body weight
      as follows: > or = 75 kg, 375 mg b.i.d.; 50-74 kg, 250 mg b.i.d.; 35-49 kg, 167
      mg b.i.d. Participants were monitored with physical examinations and prespecified
      laboratory studies by their treating physicians on a monthly basis. Follow-up
      data were collected in a central database through five regional coordinators. A
      total of 168 physicians across Canada participated in the program, and 825
      subjects who started didanosine after July 1, 1990, were included in the
      analysis. Of these, 97% were male, 88% homosexual, and 59% had a prior diagnosis
      of AIDS. Reasons for enrolling was ZDV intolerance in 39%, failure in 25%, both
      in 32%, and other in 4%. Data were prospectively collected until July 31, 1991.
      Total follow-up was 3,440 patient-months and median follow-up was 4.3 months. A
      total of 78 deaths were reported, 44 of which occurred within a month after the
      last dose of didanosine. Causes of death included AIDS-related unspecified causes
      (13 patients), MAC (11), wasting (7), AIDS-related CNS involvement other than
      OI's (7), Kaposi's sarcoma (7), Pneumocystis carinii pneumonia (6), sudden death,
      including suicides and accidents (6), lymphoma (5), toxoplasmosis (4),
      cryptococcosis (4), cytomegalovirus (3), unspecified causes (2), tuberculosis
      (1), PML (1), and disseminated histoplasmosis (1). Didanosine was discontinued in
      140 (17%) subjects during the study period due to adverse events.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7519673
TI  - Essential role of vif in establishing productive HIV-1 infection in peripheral
      blood T lymphocytes and monocyte/macrophages.
AB  - The role of vif during the establishment of human immunodeficiency virus type 1
      (HIV-1) infection of peripheral blood T lymphocytes and monocyte/macrophages was
      investigated using vif mutants of three HIV-1 proviral DNAs. Vif was found to be
      essential for the establishment of productive HIV-1 infection in peripheral blood
      T lymphocytes after cell-free infection with HXB2 and DFCI-HD, a vpr-positive,
      vpu-positive, nef-positive derivative of HXB2. A chimeric HIV-1 provirus in which
      the T-cell line-tropic env sequences in DFCI-HD were replaced with the
      macrophagetropic env of the ADA strain was constructed for studies on the role of
      vif during the establishment of HIV-1 infection in primary monocyte/macrophages.
      These studies showed that vif is also essential for the initiation of productive
      HIV-1 infection in primary monocyte/macrophage cultures after cell-free virus
      transmission. The DFCI-HD-ADA virus was shown to replicate in the CD4+ T-cell
      line Molt 4 clone 8 but not in other T-cell or monocytic cell lines, as
      previously shown for another macrophagetropic strain YU-2 (1), suggesting that
      this cell line may be useful for future studies on at least some macrophagetropic
      strains of HIV-1. The finding that vif is essential for the establishment of
      productive HIV-1 infection in primary T lymphocytes and monocyte/macrophages
      suggests that vif may be required for HIV-1 transmission and disease pathogenesis
      during natural infections and thus may be a good target for prophylactic or
      therapeutic intervention.

PMID- 7519675
TI  - [Development of bioactive functions in hydrangeae dulcis folium. II. Antiulcer,
      antiallergy, and cholagoic effects of the extract from hydrangeae dulcis folium].
AB  - In order to develop new bioactive functions of Hydrangeae Dulcis Folium, the
      fermented and dried leaves of Hydrangea macrophylla Seringe var. thunbergii
      Makino, effects of the methanolic extract from the crude drug on antiucler,
      antiallergic, cholagoic, and various pharmacological actions were investigated.
      Consequently, the methanolic extract was found to exhibit potent antiulcer,
      antiallergic, and cholagoic activities. By monitoring with these activities, it
      was found that the active constituents were contained in the lipophilic portion
      of the methanolic extract. Furthermore, the known lipophilic constituents such as
      phyllodulcin and hydrangenol were found to show little antiulcer and cholagoic
      activities, while it was also found that they showed antiallergic activity on
      Schultz-Dale reactions.

PMID- 7519676
TI  - New drug offers hope for people with schizophrenia.

PMID- 7519677
TI  - Risperidone: clinical issues in treatment.

PMID- 7519678
TI  - Vacuolar chloride regulation of an anion-selective tonoplast channel.
AB  - Fluctuations in intravacuolar chloride concentrations affected the tonoplast
      inward (anion flux into the vacuole) currents of sugar beet (Beta vulgaris).
      Rising vacuolar chloride concentrations induced increases in the levels of
      nitrate, acetate and phosphate inward currents. These currents, evoked at
      physiological vacuolar potentials, showed a linear relationship with the
      concentration of vacuolar chloride between 6 and 100 mM. Single channel currents
      revealed that rises in vacuolar chloride increased the frequency and probability
      of channel openings at a given tonoplast potential by reducing the mean closed
      time of the anion channel. In addition, there was an increase in the gating
      charge for the channel and a decrease in the free-energy favoring the transition
      of the channel from the closed to the open state. Vacuolar chloride had a very
      different effect on malate currents. Increasing chloride concentrations resulted
      in decreased frequency and open probability of the channel openings, a decrease
      in the gating charge and an increase in the mean closed time of the channel. Our
      results support the role for vacuolar chloride concentrations regulating the
      influx of anions into the vacuole, in addition to osmoregulation. The activation
      of channel activity by chloride will provide a pathway for the storage of
      nutrients, such as nitrate and phosphate into the vacuole, while the reduction of
      the malate currents will allow the use of malate for mitochondrial oxidation and
      cytoplasmic pH control.

PMID- 7519680
TI  - Characterization of the Borrelia burgdorferi RNase P RNA gene reveals a novel
      tertiary interaction.
AB  - Characterization of the RNase P RNA gene derived from Borrelia burgdorferi
      reveals covariation of the conserved nucleotides at positions corresponding to
      nucleotides 128 and 230 in Escherichia coli RNase P RNA (M1 RNA). Single base
      substitutions at either of these positions in M1 RNA resulted in a lack of
      complementation of the temperature-sensitive phenotype associated with rnpA49 in
      vivo whereas complementation was observed for the double mutant M1 RNA or wild
      type M1 RNA. Our in vitro data showed that M1 RNA harbouring a substitution at
      128 or 230 cleaved a tRNA precursor both in the absence and presence of C5 with
      reduced efficiency compared to the wild-type and the double mutant M1 RNA. We
      conclude that the nucleotides at positions 128 and 230 establish a long-range
      tertiary interaction in RNase P RNA. Our data also suggest that this interaction
      together with the identity of the nucleotide at position 230 is important for
      Pb2+ induced cleavage at specific positions in M1 RNA.

PMID- 7519679
TI  - Rapid regulation of electrolyte absorption in sweat duct.
AB  - Even though the same Cl channel (CFTR) is common to certain fluid transport
      functions that are oppositely directed, i.e., secretion and absorption, only
      fluid secretion has clearly been shown to be acutely regulated. It is now clear
      that fluid secretion activated by beta-adrenergic stimulation is controlled by
      cAMP-mediated opening and closing of CFTR-Cl channels. Since the conductance of
      the human sweat duct is almost wholly due to CFTR-Cl conductance (CFTR-GCl), we
      sought to determine whether salt absorption via CFTR-Cl channels could also be
      subject to acute regulation in this purely absorptive epithelium. After alpha
      toxin permeabilization, we found that addition of cAMP resulted in a large
      increase in Cl diffusion potentials across the apical membrane and a more than
      twofold increase in the average membrane conductance. Since the cAMP effects were
      dependent on Cl alone, not on Na, and since apical Cl conductance appears to be
      almost exclusively comprised of CFTR-GCl, we surmise that this form of
      electrolyte absorption like secretion is also subject to acute control through
      CFTR-GCl. Acute regulation of absorption involves both activation by
      phosphorylation (PKA) and inactivation by dephosphorylation (unknown endogenous
      phosphatase) of CFTR. Phosphorylation of CFTR was shown by the facts that CFTR
      GCl could be activated by cAMP and inhibited by the kinase antagonist
      staurosporine, or by removal of either substrate ATP or Mg2+ cofactor.
      Inactivation of CFTR-GCl by endogenous phosphatase(s) was indicated by a
      spontaneous but reversible loss of CFTR-GCl upon removal of cAMP. Such loss of
      CFTR-GCl activity could be prevented either by application of phosphatase
      inhibitors or by using phosphatase-resistant ATP-gamma-S as substrate to
      phosphorylate CFTR. We surmise that absorptive function is subject to rapid
      regulation which can be switched "on" and "off" acutely by a control system that
      is common to both absorptive and secretory processes and that this control is
      crucial to switching between conductive and nonconductive transport mechanisms
      during salt absorption.

PMID- 7519682
TI  - Commentary on the requirement of the testis in establishing the sensitivity of
      the canine prostate to develop BPH.

PMID- 7519683
TI  - Persistence or recurrence of symptoms after transurethral resection of the
      prostate: a urodynamic assessment.
AB  - Approximately 15 to 20% of patients who undergo transurethral resection of the
      prostate for benign prostatic hyperplasia have persistent or recurrent voiding
      symptoms requiring further therapy. To elucidate the etiology of these voiding
      abnormalities, the urodynamic findings of 129 consecutive men (mean age 72 years)
      with post-transurethral resection voiding symptoms were retrospectively analyzed
      with respect to symptoms, uroflowmetry and synchronous video pressure-flow
      cystometry. Our findings revealed obstruction in 38% of the patients, impaired
      contractility in 25% and intrinsic sphincter deficiency in 8%. Among 80 patients
      without neurological disorders involuntary bladder contractions were detected in
      50%. However, in 49 patients with neurological disorders involuntary bladder
      contractions were detected in 76%. This difference was statistically significant.
      There were 15 patients who failed 2 or more transurethral resections of the
      prostate, and involuntary bladder contractions were detected in 80%, obstruction
      in 27%, impaired contractility in 27% and sphincteric incontinence in 20%. Our
      study reveals residual or recurrent obstruction to be a contributing factor in
      less than half of all patients who fail transurethral resection of the prostate.
      Furthermore, patients with a concomitant neurological disorder and those who have
      undergone more than 1 transurethral resection of the prostate have a
      significantly higher incidence of involuntary bladder contractions. These results
      underscore the importance of obtaining complete urodynamic assessment in patients
      with persistent or recurrent voiding symptoms following transurethral resection
      of the prostate to guide appropriate therapy.

PMID- 7519685
TI  - Re: Transurethral microwave thermotherapy for management of benign prostatic
      hyperplasia: results of the United States Prostatron Cooperative Study.

PMID- 7519684
TI  - Alpha-fetoprotein producing undifferentiated carcinoma of the bladder.
AB  - We report on a rare primary undifferentiated carcinoma of the bladder producing
      alpha-fetoprotein in a woman. Definitive features included an aggressive,
      invasive and rapidly growing tumor with a hepatoid carcinomatous lesion on
      histological examination. Histopathological findings suggested that the
      multipotent transitional cell induces production of alpha-fetoprotein. The
      association of an aggressive tumor with the ability to produce this antigen
      suggests a possible benefit in measuring serum alpha-fetoprotein levels and
      examining histological sections for its expression in primary undifferentiated
      carcinoma of the bladder. Further study may indicate radical cystectomy when the
      resected specimen produces alpha-fetoprotein, particularly if tumors appear to be
      aggressive and highly vascularized as in our case.

PMID- 7519686
TI  - The requirement of the testis in establishing the sensitivity of the canine
      prostate to develop benign prostatic hyperplasia.
AB  - A long-term study on the requirement of the testis in establishing the
      sensitivity of the canine prostate to develop benign prostatic hyperplasia (BPH)
      was conducted using 23 aging beagles both with and without their testes. The dogs
      had received long-term restoration of testosterone and estrogen through silicone
      implants. When young beagles (0.5 to 1 year of age) were castrated and normal
      serum testosterone and estrogen levels restored during aging to 5 years, only 50%
      of these dogs developed BPH in the absence of their testes as opposed to 100% BPH
      development in intact controls. In addition, two-thirds of the prostates in the
      treated groups were remarkably reduced in size, being smaller than any prostate
      observed in the intact controls. If, following castration, the steroid
      restoration was withheld for 4 years during aging and subsequently administered
      starting at 5 years of age and continuing for a 6-month period, none of the
      animals developed complex BPH. Moreover, two-thirds of the prostate glands were
      reduced in size by more than 60% and were atrophied in spite of the maintenance
      of normal prostatic tissue dihydrotestosterone levels. Regardless of the time of
      steroid restoration to a castrate beagle, the periurethral zone of the canine
      prostate exhibits various degrees of atrophy indicating functional regions within
      the canine prostate that are sensitive to the requirements of the testes during
      aging. This study implicates the importance of the testis in increasing the
      probability and/or sensitivity for the full development of canine BPH.

PMID- 7519681
TI  - Filamentous hemagglutinin of Bordetella pertussis. A bacterial adhesin formed as
      a 50-nm monomeric rigid rod based on a 19-residue repeat motif rich in beta
      strands and turns.
AB  - The filamentous hemagglutinin (FHA) of Bordetella pertussis is an adhesin that
      binds the bacteria to cells of the respiratory epithelium in whooping-cough
      infections. Mature FHA is a 220 kDa secretory protein that is highly immunogenic
      and has been included in acellular vaccines. We have investigated its structure
      by combining electron microscopy and circular dichroism spectroscopy (CD) with
      computational analysis of its amino acid sequence. The FHA molecule is 50 nm in
      length and has the shape of a horseshoe nail: it has a globular head that appears
      to consist of two domains; a 35 nm-long shaft that averages 4 nm in width, but
      tapers slightly from the head end; and a small, flexible, tail. Mass measurements
      by scanning transmission electron microscopy establish that FHA is a monomer. Its
      sequence contains two regions of tandem 19-residue pseudo-repeats: the first, of
      38 cycles, starts at residue 344; the second, of 13 cycles, starts at residue
      1440. The repeat motifs are predicted to consist of short beta-strands separated
      by beta-turns, and secondary structure measurements by CD support this
      prediction. We propose a hairpin model for FHA in which the head is composed of
      the terminal domains; the shaft consists mainly of the repeat regions conformed
      as amphipathic, hyper-elongated beta-sheets, with their hydrophobic faces
      apposed; and the tail is composed of the intervening sequence. Further support
      for the model was obtained by immuno-labeling electron microscopy. The 19-residue
      repeats of FHA have features in common with the leucine-rich repeats (LRRs) that
      are present in many eukaryotic proteins, including some adhesion factors. The
      model is also compared with the two other classes of filamentous proteins that
      are rich in beta-structure, i.e. viral adhesins and two beta-helical secretory
      proteins. Our proposed structure implies how the functionally important adhesion
      sites and epitopes of FHA are distributed: its tripeptide (RGD) integrin-binding
      site is assigned to the tail; the putative hemagglutination site forms part of
      the head; and two classes of immunodominant epitopes are assigned to opposite
      ends of the molecule. Possible mechanisms are discussed for two modes of FHA
      mediated adhesion.

PMID- 7519687
TI  - Collateral development induced by repetitive brief coronary occlusion relates to
      the functional state of pre-existing collaterals.
AB  - The effects of pre-existing collaterals (PC) and the perfusion size (PS) on the
      ischemia-induced collateral development were studied in a canine model. Under
      aseptic conditions, the dogs were instrumented with pairs of ultrasonic crystals
      to measure regional wall motion in the territory of the left circumflex (LCX) and
      left anterior descending coronary artery. A micromanometer was used to measure
      left ventricular (LV) pressure. Two to 3 weeks after surgery, 2 min coronary
      occlusion (CO) of LCX was repeated every 32 min consecutively day and night using
      a remote control, motor-driven hydraulic cuff occluder. Regional wall motion and
      LV pressure were monitored via a telemetry system in 23 dogs. The functional
      state of PC was estimated by the level of % reduction of regional wall motion at
      the end of the first 2 min CO, which ranged from -11 to -141%. PS of LCX area at
      risk determined by the post mortem angiograms ranged from 35 to 54% (mean +/-
      SEM; 44 +/- 1%) of LV. Number of CO needed for collateral development ranged from
      8 to 628, and was exponentially related to the functional state of PC (r = -0.77,
      n = 23, p < 0.01), but not to PS (r = 0.43, n = 19, p = 0.07). These results
      suggest that the functional maturity of pre-existing collaterals is one of the
      major determinants of collateral development related to ischemic stimuli.

PMID- 7519688
TI  - [Vascular endothelial system--from the pathological aspects].
AB  - Endothelial functions have been paid much attention in the interaction between
      blood and vascular wall and their functional aterations play an important role in
      the development and progression of thrombosis and atherosclerosis. In this paper
      two topics in these fields, namely, the in vivo expression of tissue factor by
      endothelial cells as well as macrophages in hepatic sinusoids of rats and rabbits
      with endotoxemia, and the angiogenic mechanism in atherosclerotic intima of human
      coronary arteries and its pathophysiological significance, would be reviewed
      mainly based on our data obtained by immunohistochemical and biochemical
      examinations and molecular analyses.

PMID- 7519690
TI  - Pathophysiology of obesity-related hypertension: role of insulin and the
      sympathetic nervous system.
AB  - Reviewed herein are data supporting the hypothesis that insulin and the
      sympathoadrenal system are involved in the pathogenesis of hypertension in the
      obese. Data from the Normative Aging Study, a population-based cohort followed in
      Boston, confirm other epidemiologic reports of a direct relationship between
      upper-body obesity, hyperinsulinemia, and hypertension. Because insulin is known
      to stimulate the sympathetic nervous system (SNS), the possibility that insulin
      mediated sympathetic stimulation contributed to hypertension in the obese was
      investigated by the analysis of 24-h urinary norepinephrine (NE) excretion in
      this group. Urinary NE was directly correlated with body mass index and waist/hip
      ratio, supporting increased SNS activity in the obese. Epinephrine excretion, an
      index of adrenal medullary activity, was inversely related to obesity, and both
      high insulin and low epinephrine levels were independently correlated with lower
      levels of high-density lipoprotein cholesterol and higher levels of
      triglycerides. These results are consistent with the hypothesis that insulin
      mediated sympathetic stimulation results in hypertension from concomitant
      sympathetic stimulation of the heart, vessels, and kidney. Reciprocal changes in
      adrenal medullary function contribute to the associated dyslipidemia. Therapeutic
      strategies aimed at diminishing insulin resistance and lowering insulin levels,
      and antagonizing the effects of sympathetic stimulation on the heart, the
      vessels, and the kidneys, would appear to have a solid physiological rationale in
      the obese.

PMID- 7519692
TI  - Trandolapril in patients with essential hypertension: effects on vascular and
      cardiac structural changes.
AB  - Elevated arterial pressure levels increase the hemodynamic load on heart and
      vessels, thus leading to functional and structural abnormalities. Because cardiac
      and vascular changes increase the risk of cardiovascular disease, their reversal
      is an important target of antihypertensive therapy, even though the prognostic
      value of this regression has not been fully established. In patients with
      untreated mild-to-moderate essential hypertension and left ventricular
      hypertrophy, trandolapril, a new angiotensin-converting enzyme inhibitor, reduces
      blood pressure by decreasing total peripheral resistance and improves both
      systolic and diastolic ventricular function. The latter effect is not only
      functional in nature because, after long-term antihypertensive treatment, the
      improvement in diastolic ventricular function is detectable also after 1-month
      withdrawal of trandolapril. The concurrent reversal of left ventricular
      hypertrophy may contribute to the improved left ventricular diastolic function.
      However, plethysmographic studies suggest that long-term antihypertensive
      treatment with trandolapril is also able to reverse structural vascular changes
      in the forearm vascular bed, because after 1-month washout forearm peripheral
      resistance also is lower than in control conditions. Finally, in hypertensive
      patients, trandolapril induces significant increases in brachial artery
      compliance and diameter that persist after 1 month of withdrawal from treatment.
      The latter observation suggests that trandolapril also is able to reverse the
      structural changes of the large artery wall.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519689
TI  - Resistance to erucic acid as a selectable marker for peroxisomal activity:
      isolation of revertants of an infantile Refsum disease cell line.
AB  - A system based on the ability of cells to oxidize very long-chain fatty acids
      (VLCFA) was developed to select in vitro normal human fibroblasts from
      fibroblasts of patients suffering from peroxisomal disorders with multienzymatic
      deficiencies: Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum
      disease (IRD). Cells treated with various concentrations of erucic acid (C22:1 n
      9) revealed an enhanced toxicity of this fatty acid for the fibroblasts of
      patients compared with normal cells. This differential toxicity is correlated
      with variable accumulations of C22:1 n-9 and the absence of beta-oxidation
      products in the mutants. Revertants from clonal IRD cell lines were isolated in
      the selective medium at frequencies ranging from 3 x 10(-7) to 4 x 10(-6)
      depending on the line. After six weeks of growth in the absence of selective
      pressure, the variants exhibited a resistance level to C22:1 n-9 identical to
      that of normal cells. Furthermore, beta-oxidation of VLCFA is re-established in
      these selected cells as well as dihydroxyacetone phosphate acyltransferase
      activity. Immunoblot experiments also demonstrated a restored pattern of acyl-CoA
      oxidase molecular forms. Last, immunofluorescence studies revealed the presence
      of cytoplasmic structures that were absent in the original IRD cells. Thus, both
      the deficiencies in metabolic pathways and paucity of the organelle are at least
      partially corrected in the selected clones.

PMID- 7519691
TI  - Twenty-four-hour ambulatory blood pressure monitoring and antihypertensive
      treatment: focus on ACE inhibitors.
AB  - The use of ambulatory blood pressure monitoring in clinical studies offers some
      advantages in comparison to the clinic blood pressure measurement. In fact, this
      approach does not induce any alerting reaction and provides 24-h blood pressure
      values that are more reproducible and not affected by the placebo effect. This
      allows a better evaluation of blood pressure under antihypertensive treatment and
      an optimization of the number of patients to be studied in pharmacologic trials.
      In a recent double-blind, parallel-group study, ambulatory blood pressure
      monitoring was used to investigate the antihypertensive efficacy of a new
      angiotensin-converting enzyme inhibitor, trandolapril, in 62 mild and moderate
      hypertensive patients. After a washout period, patients received trandolapril, 2
      mg o.d., or placebo for 6 weeks, followed by a second washout period. Clinic and
      24-h blood pressures were assessed at the end of each period. In comparing the
      pre- and post-treatment period, trandolapril significantly reduced clinic and 24
      h systolic and diastolic blood pressures. The fall was evident throughout the 24
      h and was statistically significant also in the last 4 h of blood pressure
      monitoring. The placebo group did not show any significant blood pressure change.
      Thus, trandolapril, 2 mg once daily, is effective in reducing blood pressure. Its
      efficacy over 24 h is better documented by 24-h blood pressure monitoring than by
      isolated clinic blood pressure measurement.

PMID- 7519693
TI  - ACE inhibition and physical exercise: studies on physical work capacity, energy
      metabolism, and maximum oxygen uptake in well-trained, healthy subjects.
AB  - We investigated the effects of the angiotensin-converting enzyme (ACE) inhibitor
      trandolapril (2 mg/o.d.) on the physical work capacity (PWC), the received
      perception of exertion (RPE), as well as parameters determining physical
      performance (i.e., energy metabolism, lactate production, and oxygen uptake) in
      well-trained, healthy subjects. Twenty male sports students underwent a bicycle
      spiroergometry until exhaustion to determine maximum work load, maximum oxygen
      uptake, lactate threshold, and parameters of energy metabolism. The identical
      protocol was repeated after a 14-day treatment period with 2 mg of trandolapril
      o.d. or placebo. Treatment with the ACE inhibitor did not significantly alter
      maximum PWC, RPE, 4.0 mmol/L lactate threshold, heart rate, maximum oxygen
      uptake, plasma levels of total cholesterol, triglycerides, free fatty acids,
      glucose, insulin, cortisol, and human growth hormone. In the presence of the ACE
      inhibitor, the exercise-induced increase in systolic blood pressure was
      moderately (n.s.) blunted (204 +/- 7 versus 192 +/- 7 mm Hg). Treatment with the
      ACE inhibitor did not impair physical performance and RPE. This favorable profile
      of action was accompanied by no alterations in maximum oxygen uptake and
      parameters of energy metabolism at all levels of exercise intensity. Therefore,
      it may be concluded that antihypertensive treatment with an ACE inhibitor should
      be primarily considered in physically active patients.

PMID- 7519697
TI  - Vascular renin-angiotensin system and sympathetic nervous system activity in
      human hypertension.
AB  - Experimental data indicate the existence of a vascular tissue renin-angiotensin
      system in several different vessels from various animal models. Active renin can
      be locally synthesized into the vessel wall or taken up from circulating plasma
      to produce vascular angiotensin II. Using the human forearm technique, we
      produced evidence indicating the release of active and inactive renin and of
      angiotensin II from the vessels of hypertensive patients. Moreover, the
      production of vascular angiotensin II seems to be strictly correlated to the
      circulating renin profile, suggesting the possibility that vascular renin might
      be at least partially taken up from plasma. To investigate a possible function of
      the vascular renin-angiotensin system, we studied its interaction with
      sympathetic neurotransmission in essential hypertensive patients. In line with
      animal studies, vascular angiotensin II increases the vasoconstriction induced by
      the stimulation of the sympathetic nervous system through the potentiation of
      noradrenaline release at a presynaptic level, and this effect seems to be
      mediated by beta-adrenoceptor activation. This facilitating effect on sympathetic
      neurotransmission exerted by vascular angiotensin II can be antagonized by both
      angiotensin II antagonists and angiotensin-converting enzyme inhibitors.

PMID- 7519696
TI  - Cardiac benefits of ACE inhibitors and calcium antagonists alone and in
      combination.
AB  - No large mortality trials have been completed comparing either angiotensin
      converting enzyme (ACE) inhibitors or calcium-entry-blocking drugs with placebo
      or established drugs in the treatment of hypertension, although these are now
      about to start. Several large mortality studies in ischemic heart disease or
      cardiac failure allow us to make some general comments in favor of ACE inhibitors
      separately, or in favor of some calcium-channel blockers separately. There is no
      mortality evidence for first-generation dihydropyridines, but rather the reverse.
      There is good evidence in favor of verapamil and diltiazem, perhaps because of
      their lack of peripheral vasodilatation and reflex tachycardia. No large studies
      have been carried out comparing calcium-channel blockers with ACE inhibitors.

PMID- 7519694
TI  - Possible synergistic effect of ACE inhibition and calcium-channel blockade on
      insulin sensitivity in insulin-resistant type II diabetic hypertensive patients.
AB  - So-called insulin resistance is a frequent phenomenon and a marker of increased
      risk for both type II diabetes mellitus and atherosclerosis. Today, insulin
      resistance is widely understood as a tissue- and pathway-specific defect of
      insulin-stimulated glucose uptake into skeletal muscle that is compensated for by
      hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic,
      diabetogenic, and atherogenic processes. Additional defects of insulin-stimulated
      muscle blood flow and cellular kation balance are presently attracting increasing
      awareness. Clinical and experimental evidence suggests that angiotensin
      converting enzyme (ACE) inhibition ameliorates both insulin-stimulated skeletal
      muscle glucose uptake and blood flow in insulin-resistant states by a direct
      stimulation of cellular glucose uptake, which appears to be kinin-mediated. This
      improvement of insulin sensitivity could mean not only improvement of glucose
      metabolism, but also reduction of chronically elevated serum insulin and the
      ensuing atherogenic consequences (hyper- and dyslipidemia, sympathetic
      overactivity, growth of vascular smooth-muscle cells, hypertension, etc.). Ca(2+)
      channel blockers that do not increase heart rate appear to exert direct
      antiatherogenic effects while being metabolically neutral. Thus, the combination
      of Ca(2+)-channel blockade by sustained release verapamil and ACE inhibition by
      trandolapril in insulin-resistant type II diabetic patients with essential
      hypertension appears to be promising in terms of possible synergistic
      effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519698
TI  - Characterization and decomposition of voltage-activated ionic currents using a
      fitting numerical method.
AB  - The application of a computer-based numerical method for fast determination of
      the kinetic parameters of voltage-activated ionic currents is described. Currents
      with different kinetics and ionic backgrounds are fitted satisfactorily with
      Hodgkin-Huxley-like functions, and multicomponent currents are decomposed. The
      method offers a way to separate ionic-current components without pharmacological
      isolation.

PMID- 7519699
TI  - Biocytin: a neuronal tracer compatible with rapid decalcification procedures.
AB  - The compatibility of neuronal tract-tracing and decalcification procedures was
      examined in salamander nasal chemosensory systems. Biocytin, but not horseradish
      peroxidase, retained its labeling capacity following rapid decalcification of the
      cranial bone. The combination of biocytin tract-tracing and decalcification
      procedures allows the visualization of labeled neurons and/or their projections
      within bony regions of intact specimens.

PMID- 7519695
TI  - Antihypertensive therapy and progression of diabetic renal disease.
AB  - A number of changes in intrarenal hemodynamics and morphology are characteristic
      of diabetic nephropathy. These changes include: increases in intraglomerular
      pressure and volume, glomerular capillary permeability to macromolecules, and
      mesangial matrix expansion. Most antihypertensive drugs attenuate some of the
      increases in these parameters. Certain antihypertensive agents, however, have
      effects on all these parameters. Studies in animal models of diabetes demonstrate
      that the angiotensin-converting enzyme (ACE) inhibitors reduce both
      intraglomerular volume and pressure, mesangial matrix expansion, and albuminuria.
      The calcium antagonists TA-3090 (diltiazem-like) and verapamil recently have been
      shown to have most of these effects. Conversely, the dihydropyridine calcium
      antagonists (nifedipine, felodipine, nitrendipine) do not attenuate increases in
      most of these parameters. In several clinical studies, nifedipine either did not
      affect or increased urinary albumin excretion in diabetic patients with renal
      insufficiency. Moreover, in animal models of diabetes, most dihydropyridine
      compounds do not prevent progression of glomerulosclerosis in spite of blood
      pressure control. Although the majority of clinical studies support the concept
      that reduction of arterial pressure preserves renal function, recent long-term
      clinical studies show that ACE inhibitors and heart-rate-lowering calcium
      antagonists (diltiazem, verapamil) attenuate progression of diabetes to a greater
      extent than most other agents do.

PMID- 7519701
TI  - Differences between young and aged mice in susceptibility to Friend virus.
AB  - Friend virus (FV) is a murine leukemia virus that infects progenitor red blood
      cells and causes an erythroleukemia in susceptible mouse strains, resulting in
      splenomegaly. Several genetic loci of the host have been identified that affect
      erythroleukemia development, differentiation status of target cells and virus
      replication. Since age may change expression of these loci, age may affect FV
      disease. To explore this possibility, FV expression in four genetically diverse
      strains of mice of different ages was examined. Extent of viral replication and
      of disease were evaluated by measuring spleen focus forming units (SFFU), spleen
      weight and reverse transcriptase (RT) activity in target organs. Young DBA/2 and
      (C57BL/6 x DBA/2)F1 mice exhibited a greater level of virus expression than their
      aged counterparts in all parameters investigated. Young CBA/Ca mice had slightly
      higher spleen weights and SFFU values than aged CBA/Ca mice, but a definitive age
      related change was not observed in the RT activity of the target organs. C57BL/6
      mice, which are genetically resistant to the development of FV-induced
      erythroleukemia, exhibited a limited degree of virus replication that was not
      effected by the age of the animal. Our results indicate that the age of the
      mouse, as well as the genetic background, can contribute to the level of
      susceptibility to FV.

PMID- 7519702
TI  - Characteristics of the anxiolytic effects of buspirone in high- and low-anxious
      normal humans assessed by frontal midline theta activity.
AB  - Fmtheta is a distinct theta activity in the frontal midline area that appears
      during performance of mental tasks. It is suggested that relief from anxiety
      might be reflected in the appearance of Fmtheta. In the present study, the
      anxiolytic effects of buspirone were investigated using 24 male university
      students with (Fmtheta group, n = 12) and without (non-Fmtheta group, n = 12)
      Fmtheta. The subjects were given placebo, buspirone 5 mg and 15 mg in a double
      blind, crossover design. Blood samples were obtained, scores were made on the
      State Trait Anxiety Inventory (STAI), and EEGs were recorded before and during
      performance of an arithmetic addition. The test was repeated twice: before and 1
      h after drug administration. In the Fmtheta group, buspirone dose-dependently
      produced a decrease in plasma 5-HT and 5-HIAA concentrations and in state anxiety
      scores and an increase in Fmtheta amounts. In the non-Fmtheta group, however,
      there were no differences in these items except for 5-HT concentration before and
      after buspirone administration. These results suggest that anxiety in the Fmtheta
      group is mainly correlated with 5-HT1A receptor function, and that buspirone may
      have anxiolytic effects in patients with reactive anxiety but not those with
      endogenous anxiety.

PMID- 7519703
TI  - [The antigen of pernicious anemia is identified].

PMID- 7519700
TI  - Influence of long-term treatment with L-deprenyl on the age-dependent changes in
      rat brain microanatomy.
AB  - The present study was designed to assess whether treatment with the monoamine
      oxidase-B (MAO-B) inhibitor L-deprenyl, which has been documented to increase
      both mean and maximum survival in aged rats as well as sexual performance and
      cognitive function, has any effect on the age-related microanatomical changes
      occurring in the rat brain. Male Sprague-Dawley rats received a subcutaneous
      injection of 0.25 mg/kg L-deprenyl every other day from the 19th to the 24th
      month of age. Age-matched control rats were injected with saline, whereas 11
      month-old untreated rats were used as an adult reference group. Both body and
      brain weight were increased as a function of age, and they were unaffected by
      treatment with L-deprenyl. The density of nerve cell profiles in the frontal
      cortex, in the CA-1 and CA-3 subfields of the hippocampus, in the dentate gyrus
      and in the cerebellar cortex were decreased in aged rats in comparison with adult
      rats. The density of nerve cell profiles in the above brain areas of L-deprenyl
      treated rats was not significantly higher in comparison with age-matched control
      animals with the exception of Purkinje neuron profiles. The intensity of Nissl's
      staining, which may be related to the protein synthetic capabilities of nerve
      cells, is reduced within pyramidal neurons of the hippocampus and Purkinje
      neurons of the cerebellar cortex of aged rats. The intensity of Nissl's staining
      in L-deprenyl-treated rats was not different from adult rats. Lipofuscin
      deposition was significantly increased within the cytoplasm of pyramidal neurons
      of the frontal cortex, of the CA-3 subfield of the hippocampus and of Purkinje
      neurons of the cerebellar cortex. L-Deprenyl administration decreased lipofuscin
      accumulation within the cytoplasm of the above mentioned nerve cell types. The
      density of sulphide-silver staining in the intrahippocampal pathway of mossy
      fibres, which participate in the elaboration of passive avoidance responses, is
      decreased in aged rats. Treatment with L-deprenyl counters this age-related
      reduction. The above results suggest that long-term treatment with L-deprenyl is
      able to counter the expression of some microanatomical changes typical of aging
      brain.

PMID- 7519704
TI  - [Myeloid growth factors. New indications with many questions].

PMID- 7519705
TI  - Reaction to gelatin plasma expanders.

PMID- 7519706
TI  - Reactions to gelatin plasma expanders.

PMID- 7519708
TI  - Reactions to gelatin plasma expanders.

PMID- 7519707
TI  - Reactions to gelatin plasma expanders.

PMID- 7519709
TI  - Prevalence of hepatitis C antibodies in health-care workers.

PMID- 7519710
TI  - Prevalence of hepatitis C antibodies in health-care workers.

PMID- 7519711
TI  - Prevalence of hepatitis C antibodies in health-care workers. Italian Study Group
      on Blood-borne Occupational Risk in Dialysis.

PMID- 7519712
TI  - Epitopes of GAD 65 in insulin-dependent diabetes mellitus.

PMID- 7519713
TI  - Reducing hospital beds for patients with advanced cancer.

PMID- 7519714
TI  - Can wound healing be a paradigm for tissue repair?
AB  - This paper is written in the hope, if not the conviction, that it will be helpful
      to investigators of muscle physiology and development. Its thesis is that cell
      growth, connective tissue matrix deposition, and angiogenesis are stimulated in
      wounds in response to NAD+ depletion caused by a burst in lactate generation. We
      surmise that muscle development may also involve this metabolic control.

PMID- 7519715
TI  - Characterization of hemolytic and antifungal substance, cepalycin, from
      Pseudomonas cepacia.
AB  - Hemolytic and antifungal substances, cepalycin I and cepalycin II, have been
      isolated from Pseudomonas cepacia JN106. A large amount of cepalycins were
      produced by growing the cells on 1% glycerin-nutrient agar medium covered with a
      cellophane membrane. The cell-washed supernatant was applied to an Amberlite XAD2
      column, and cepalycins were eluted with 70% ethanol containing 1mM HCl.
      Cepalycins were separated by reverse phase HPLC in two fractions which were
      designated as cepalycin I and cepalycin II. The two cepalycins have
      indistinguishable UV absorption spectra but have different levels of hemolytic
      activity relative to the UV absorption. From the inhibition of hemolytic activity
      of cepalycin by sterols, both cepalycins were suggested to interact with
      cholesterol in erythrocyte membrane. Such an interaction may contribute to their
      hemolytic and antifungal activities.

PMID- 7519716
TI  - Production of slime polysaccharides by Shigella dysenteriae type 1.
AB  - Electron microscopy of ruthenium red-stained ultrathin section of strains of
      Shigella dysenteriae type 1 grown in the Casamino Acids-yeast extract broth
      medium showed the presence of an extracellular slime layer. The slime appeared as
      a dense sheath covering bacteria. The presence of slime promoted hemagglutinating
      activity of the bacteria. The slime polysaccharide (SPS) isolated from the cell
      free culture supernatant or the bacterial surface was less than 162,000 daltons
      in size and immunochemically similar. The SPS showed cross-reaction with
      lipopolysaccharide (LPS) antigen in immunological tests; however, it also
      appeared to be different from LPS since it did not contain 2-keto-3
      deoxyoctonate, a core sugar of LPS. A different pattern of separation from LPS
      was also observed by silver staining of SDS-polyacrylamide gels. From these data
      it appeared that either LPS and SPS are contaminated with each other or that SPS
      is the polysaccharide portion of LPS.

PMID- 7519717
TI  - Resistance to pseudorabies virus with enhanced interferon production and natural
      killer cell activity in mice treated with serum thymic factor.
AB  - Susceptibility to pseudorabies virus (PRV) infection in mice, which were
      continuously depleted of natural killer (NK) cell activity by injection of anti
      asialo GM1, was examined. Effects of serum thymic factor (FTS) on susceptibility
      of mice to PRV were also investigated. In mice with depleted NK cell activity,
      the mortality of PRV-infected mice was markedly high, whereas that of FTS
      pretreated mice was significantly lower than the controls. Reduced susceptibility
      to PRV was demonstrated in mice treated with anti-asialo GM1 antisera before the
      PRV infection. Such a reduced susceptibility was not observed in mice inoculated
      with the antisera on day 1 post-infection (PI). To analyze the FTS-induced
      resistance to PRV infection, NK cell activity, macrophage activity, and
      interferon (IFN) productions were studied. Interferon production and NK cell
      activity were enhanced in the FTS-pretreated mice, suggesting that interferon may
      play an important role in this FTS-induced resistance to PRV infection.

PMID- 7519719
TI  - [NO, endogenous messenger and cell poison].

PMID- 7519720
TI  - [Primary extragonadal germ cell tumors. Clinical manifestations, differential
      diagnosis and therapy].
AB  - BACKGROUND: Primary extragonadal germ cell tumors are a rare malignant disease in
      young males. They account for only 1 to 4% of all germ cell tumors. PATIENTS AND
      METHODS: In this paper we describe three selected cases of primary extragonadal
      germ cell tumors. The literature is reviewed with regard to clinical features,
      differential diagnosis and treatment. RESULTS: Tumor markers alpha-fetoprotein
      and human chorionic gonadotropin are of considerable diagnostic value if disease
      distribution is considered. With cisplatin-based combination chemotherapy similar
      disease-free survival rates are achieved as for testicular tumors with poor
      prognosis metastatic disease. Surgical procedures play a role as adjunctive
      modality. CONCLUSIONS: If young males present with a mass in the retroperitoneum
      or in the anterosuperior mediastinum, a primary extragonadal germ cell tumor,
      should be taken into consideration. Tumors of both localisations have distinct
      clinical features but carry a similar prognosis. Patients benefit from the
      cumulative experience of a specialist unit.

PMID- 7519718
TI  - Anti-human IgE monoclonal antibodies recognizing epitopes related to the binding
      sites of high and low affinity IgE receptors.
AB  - Anti-human IgE monoclonal antibodies (mAbs) were produced and eight clones
      recognizing epitopes on native IgE were selected. Epitopes were mapped by a
      competitive inhibition enzyme-linked immunosorbent assay, Western blotting and a
      multi-pin peptide technology. Four sites (one each in the C epsilon 1, C epsilon
      2, C epsilon 2/C epsilon 3 junction and C epsilon 3) were recognized by the mAbs.
      The relationship between the four epitopes and the binding sites of high and low
      affinity IgE receptors (Fc epsilon RI and Fc epsilon RII, respectively) was
      studied using a monovalent Fab fragment of each mAb as a binding inhibitor. The
      IgE-Fc epsilon RII binding was clearly inhibited by the mAb recognizing the C
      epsilon 2/C epsilon 3 junction, suggesting that Fc epsilon RII binds to a rather
      limited area around the C epsilon 2/C epsilon 3 junction. The IgE-Fc epsilon RI
      binding, on the other hand, was scarcely inhibited by any single mAb. However,
      the binding was inhibited when the epitope in C epsilon 2 was blocked
      simultaneously with that at the C epsilon 2/C epsilon 3 junction or with that in
      C epsilon 3, indicating that these three distinct epitopes are related to the Fc
      epsilon RI binding sites. When these three epitopes were shown in the stereograph
      of human IgE, the Fc epsilon RI binding area was spread largely on the groove
      side between C epsilon 2 and C epsilon 3 domains. These results suggest that Fc
      epsilon RI acquires the high affinity through multiple bindings.

PMID- 7519721
TI  - Isolation and characterization of phosphoprotein phosphatase 1 from alfalfa.
AB  - Protein phosphatases are central regulatory components of diverse processes in
      eukaryotes and are among the most highly conserved proteins known. In this paper,
      we report the cloning and sequencing of a type 1 protein phosphatase (pp1Ms) cDNA
      from alfalfa. Southern analysis indicates the presence of a gene family of PP1
      proteins in alfalfa. The pp1Ms open reading frame is very similar to one of five
      predicted Arabidopsis type 1 protein phosphatases, indicating that different
      subtypes are individually conserved. Expression of the alfalfa pp1Ms in a
      temperature-sensitive Schizosaccharomyces pombe PP1 mutant, dis2-11, revealed no
      complementation, suggesting that PP1Ms is not involved in mitotic regulation. In
      different plant organs, different pp1Ms transcript levels were observed; in
      contrast, mRNA levels remained constant in all phases of the cell cycle and in
      logarithmically growing cells. However, when cells entered stationary phase pp1Ms
      transcript levels decreased considerably.

PMID- 7519724
TI  - Involvement of a cAMP-responsive DNA element in mediating TRH responsiveness of
      the human thyrotropin alpha-subunit gene.
AB  - TRH is known to stimulate the transcription of the TSH gene in pituitary cells.
      To examine TRH-responsive elements of the human TSH alpha-subunit gene, we have
      used transient transfection of GH3 rat pituitary tumor cells. Using this system,
      TRH treatment stimulated expression of a reporter gene containing 846 base pairs
      from the 5'-flanking region of the human glycoprotein hormone alpha-subunit gene
      linked to luciferase. Analysis of 5'-deletions of the alpha-subunit sequence
      revealed that at least two DNA regions with upstream limits between positions 
      223 to -190 and positions -151 to -135 are important for regulation by TRH. The
      more proximal region includes a previously defined cAMP-response element (CRE)
      while the more upstream region contains an element with sequence similarity to
      the binding site for the pituitary transcription factor, Pit-1. The TRH
      responsiveness of each individual region was tested by inserting fragments
      upstream of a thymidine kinase-luciferase reporter gene. The -151 to -100 region
      had basal enhancer activity and permitted a 3.4-fold response to TRH. The -223 to
      -168 region did not permit a TRH response, but possessed basal enhancer activity.
      The combination of both regions resulted in a 5-fold stimulation by TRH. To
      assess the contributions of different signal transduction pathways, various
      combinations of treatments were examined. Combined treatment with TRH and
      forskolin led to an additive activity. Treatment with TRH plus phorbol 12
      myristate-13-acetate resulted in the same level of reporter gene activity as with
      either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519725
TI  - Do specific nucleotide bases constitute the centromere?
AB  - It is becoming increasingly clear that the underlying base composition of the DNA
      located in the centromere region is vastly different in different organisms. The
      chromosomes of related species or even the various chromosomes of the same
      species differ widely in their so-called centromeric DNA. Yet all centromeres
      appear physically alike and perform similar functions. The present communication
      proposes that the physical properties of the centromere are not due to its base
      composition but due to stereophysical make-up of the DNA segment constituting the
      centromere. This unique make up might reflect some physical parameter, like
      curvature, of the DNA present in the centromere constriction. It is further
      proposed that a proteinaceous factor, centromerase, is responsible for holding
      the centromeres as one unit until meta-anaphase.

PMID- 7519723
TI  - Mammary gland factor activated by prolactin on mammary epithelial cells and acute
      phase response factor activated by interleukin-6 in liver cells share DNA binding
      and transactivation potential.
AB  - We have studied transcription factors that are coupled to the activation of
      cytokine receptors in liver and in mammary epithelial cells. Interleukin-6 (IL-6)
      causes the rapid activation of the acute-phase response factor (APRF) in the
      liver of animals during acute inflammation and in cultured human hepatoma cells
      (HepG2) and induces the transcription of the acute-phase protein genes, e.g.
      alpha 2-macroglobulin (alpha 2-M). In the mammary gland and in cultured HC11
      mammary epithelial cells, milk protein genes, e.g. beta-casein, are induced by
      the lactogenic hormones, insulin, glucocorticoids, and PRL. The induction of the
      beta-casein gene promoter is preceded by the activation of the mammary gland
      factor (MGF). We have compared the DNA binding sequences of APRF and MGF, 5'
      CTTCTT/GGGAATT-3', and have found that they coincide in 11 of 12 positions.
      Bandshift experiments and oligonucleotide competition experiments showed that
      both factors, MGF and APRF, are able to bind to the IL-6 response element of the
      alpha 2-M gene promoter and to the lactogenic hormone response element of the
      beta-casein gene promoter with very similar specificities. Partial proteolytic
      digestion of APRF and MGF DNA complexes yielded similar clipping patterns. The UV
      cross-linked DNA complexes of both transcription factors were of the same
      apparent molecular mass. IL-6 activation of APRF in HepG2 cells can be observed
      within minutes. MGF induction by PRL in HC11 cells occurs with similar kinetics.
      The synergistic action of glucocorticoids and PRL is necessary for the induction
      of the beta-casein gene, but PRL is sufficient for MGF activation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7519722
TI  - [Chimeric toxin of the A-subunit of viscumin and the B-subunit of ricin].
AB  - A chimeric toxic protein was prepared from the mistletoe lectin I A-chain and
      ricin B-chain by using the disulfide exchange reaction. Ricin and chimeric
      protein were indistinguishable in binding to immobilized asialofetuin in ELISA.
      The chimeric protein was more toxic for Jurkat cells than native mistletoe lectin
      I, but not as effective as native ricin. In the presence of NH4Cl, which enhances
      the toxicity of some toxins and immunotoxins, but does not influence ricin
      toxicity, both ricin and chimeric toxin had equal cytotoxic activity. The
      possibility is discussed that the ricin B-chain protects the ricin A-chain from
      degradation during delivery from the cell surface to the place where it is
      translocated into the cytosol.

PMID- 7519726
TI  - Evaluation of the antimutagenic potential of anthracene: in vitro and ex vivo
      studies.
AB  - The present study was undertaken in order to evaluate the in vitro and ex vivo
      antimutagenicity of anthracene against the food-borne carcinogen IQ (2-amino-3
      methylimidazo[4,5-f]quinoline). Anthracene caused a marked, concentration
      dependent decrease in the mutagenicity of IQ in the Ames test, whether hepatic S9
      or isolated microsomes from Aroclor 1254-induced rats served as the activation
      systems. Anthracene gave rise to a concentration-dependent inhibition of the 0
      deethylation of ethoxyresorufin, a diagnostic probe for CYP1A (cytochrome P450
      family 1, subfamily A) activity, and of the metabolic activation of Glu-P-1 (2
      amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole, a diagnostic probe for CYP1A2.
      When microsomal metabolism of IQ was terminated by menadione, incorporation of
      anthracene into the incubation mixture once again inhibited the mutagenicity of
      IQ. All the above observations indicate that anthracene owes its antimutagenic
      response against IQ to: (a) inhibition of its CYP1A-mediated activation and (b)
      direct interaction between anthracene and the reactive intermediate(s) of IQ
      leading to their inactivation. Treatment of rats with anthracene did not greatly
      influence the ability of hepatic preparations to bioactivate IQ to mutagens.
      Similarly, administration of anthracene 2 h before sacrifice to Aroclor 1254
      pretreated rats, did not modulate the hepatic activation of IQ. These findings
      demonstrate that the in vitro mechanisms of the antimutagenicity of anthracene
      are not operative in vivo, and further illustrate the inadequacy of in vitro
      studies, conducted in isolation, in predicting such effects.

PMID- 7519727
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. Mutagenicity and carcinogenicity of topoisomerase-interactive
      agents.
AB  - Drugs that interact with DNA topoisomerases I and II hold great promise for the
      treatment of cancer, however, like many other anti-cancer agents, they are a
      double-edged sword and may themselves cause mutation and cancer. In vitro studies
      show that clinically effective agents, such as etoposide, doxorubicin and others,
      stabilize a ternary complex where topoisomerase II is covalently linked to DNA.
      This complex represents an intermediate in the topoisomerase-II catalyzed DNA
      supercoil relaxation reaction. Camptothecin and its analogues stabilize a similar
      ternary complex, in vitro, consisting of topoisomerase I covalently linked to DNA
      at single-strand breaks. Short-term tests of genotoxicity confirm that
      topoisomerase-interactive agents are mutagenic and suggest common mechanisms by
      which they induce mutation and selectively kill tumor cells. These agents induce
      sister-chromatid exchange, chromosomal aberrations and mutations in specific
      mammalian genes. Their propensity to induce small colonies in the L5178/TK+/(-)
      3.7.2C assay implies that topoisomerase-interactive agents induce large DNA
      rearrangements and deletions. These may result from topoisomerase-subunit
      exchange at drug-stabilized ternary complexes or from attempts by the cell to
      bypass the replication block caused by stabilized ternary complexes. Studies in
      bacterial mutation assays suggest that topoisomerase-interactive agents may also
      induce mutations, albeit at a lower rate, through simple DNA intercalation or via
      generation of oxygen free radicals. Second malignancies observed in patients
      previously treated with topoisomerase II interactive agents suggest these may be
      an important clinical consequence of their capacity to induce mutation. In
      particular, a unique form of acute myelogenous leukemia is observed at strikingly
      high frequencies after treatment with relatively high doses of the
      epipodophyllotoxins etoposide and teniposide. This form of AML has been reported
      after the uses of other classes of topoisomerase-interactive agents as well.
      Cancer induction is therefore a toxic consequence predicted by short-term tests
      of genotoxicity and should be weighed against the potential therapeutic benefits
      of topoisomerase-interactive agents.

PMID- 7519728
TI  - Induction of tandem-base change mutations.
AB  - Four databases with sequence changes for 12000 mutations in mammalian and
      bacterial cells were searched for genotoxic agents inducing tandem mutations, in
      which two adjacent base pairs are changed. Ultraviolet light induces about one CC
      > TT per 10-20 mutations, and other tandem-base changes at about half that
      frequency. There is strong evidence that cis-diammine dichloroplatinum (II)
      induces tandems. These results suggest that tandem-base changes are induced by
      agents that damage two adjacent base pairs in DNA. Tandems, particularly CC > TT,
      can be used as indicators of exposure to ultraviolet light, as in genes in skin
      cells exposed to sunlight. Oxidizing agents such as superoxide and ionizing
      radiation do not induce a significant level of tandem-base changes (such as CC >
      TT) in double-strand DNA, so such mutations are not a useful indicator of
      exposure to mutagens of this type. All conclusions are equally valid for
      bacterial and mammalian cells.

PMID- 7519729
TI  - Mutation induction by accelerated heavy ions in bacteria.
AB  - Induction of lacI- forward mutations in Escherichia coli Ymcl and his(-)-->his+
      reversions in Salmonella typhimurium TA102 was investigated after irradiation
      with heavy ions in the range of Z = 1-36. Particle specific energies (E) were in
      the range of 1-600 MeV/u. A strong dependence of the mutation induction cross
      section (sigma m) on both particle energy and LETinfinity was observed. The
      results suggest that two different ranges of LETinfinity can be distinguished. In
      the range of high LETinfinity (> 100 keV/micron) sigma m increases with
      increasing specific particle energy if LETinfinity is kept constant (Fe ions as
      compared with carbon ions or alpha-particles). In the range of low LETinfinity (<
      100 keV/micron) sigma m decreases with increasing energy (Ne ions as compared
      with He ions).

PMID- 7519730
TI  - Effects of dietary selenium on differentiation, morphology and functions of
      spermatozoa of the house rat, Rattus rattus L.
AB  - Ingestion of 2 ppm and 4 ppm selenium in the diet by the house rat, Rattus
      rattus, for 5 weeks caused a dose-dependent reduction in its body weight,
      testicular and cauda epididymidis weights, concentration, motility and percentage
      of live spermatozoa with a simultaneous increase in the percentage of their
      abnormal forms. Compared to 1.39% abnormal spermatozoa in cauda epididymidis in
      untreated control rats, 3.89% and 24.64% abnormal spermatozoa were observed in
      rats with 2 ppm and 4 ppm dietary selenium respectively. Ingestion of 4 ppm
      selenium had no significant effect on abnormalities of the head and neck regions
      but abnormalities of the midpiece region and multiple abnormalities increased
      significantly. Analysis of the various stages of differentiation of spermatids in
      the testis has revealed that with 4 ppm dietary selenium, the abnormalities are
      induced mainly in the midpiece region of the flagellum which is a site of energy
      production.

PMID- 7519731
TI  - Fjord-region diol-epoxides of benzo[c]chrysene are potent inducers of micronuclei
      in murine bone marrow.
AB  - Vicinal diol-epoxides are the best established carcinogenic metabolites of
      polycyclic aromatic hydrocarbons. Numerous studies have demonstrated their high
      genotoxic activity in various in vitro test systems. However, in vivo
      mutagenicity data are not available. The fjord-region diol-epoxides of
      benzo[c]chrysene combine high mutagenic activity in vitro with high hydrolytic
      stability. They were tested for the induction of micronuclei in the bone marrow
      following intraperitoneal administration to NMRI mice. The anti diastereomer of
      the diol-epoxide enhanced the frequency of micronucleated polychromatic
      erythrocytes strongly (7-19-fold above the value in untreated controls) over a
      very wide dose range (2.5-300 mumol/kg body weight). The syn diastereomer
      demonstrated similar effects, but required about 5 times higher doses. The
      corresponding proximate mutagen, benzo[c]chrysene-trans-9,10-dihydrodiol, was
      only moderately active, whereas the positive control substance, benzo[a]pyrene
      trans-7,8-dihydrodiol, was strongly active. The study indicates that
      intraperitoneally administered diol-epoxides of benzo[c]chrysene may reach the
      bone marrow. Therefore, it will be possible to study the influence of metabolic
      modulation, e.g. by enzyme induction, on the effects of these ultimate mutagens
      and their metabolic precursors in vivo.

PMID- 7519732
TI  - The formation of one-G deletions as a consequence of single-oxygen-induced DNA
      damage.
AB  - Single-stranded M13mp10 DNA containing a 144-bp mutational target sequence in the
      lacZ alpha gene was treated with singlet oxygen (1O2) generated by
      thermodissociation of the endoperoxide of 3,3'-(1,4-naphthalene-1,4
      diyl)dipropionate (NDPO2). After transfection to non-SOS-induced E. coli cells,
      32 mutants preselected for a mutation in the 144-bp target were collected and
      analyzed by DNA sequencing. One-G deletions represented the predominant type of
      mutation accounting for 50% of the mutations analyzed. The remaining part
      appeared to consist of base substitutions, i.e. G-->T transversions (34%), C-->T
      transitions (12.5%) and one T-->C transition (3%). Sixty percent of the mutations
      were found in two major mutational hotspots. We conclude that the predominant one
      G deletions are due to a guanine reaction product which might be specific for
      1O2.

PMID- 7519733
TI  - Expression of genes carried by pR plasmid in damaged E. coli and mouse cells.
AB  - In LTA mouse cells pR plasmid constitutively expresses itself resulting in
      protection against typical SOS inducers (UV, 4NQO) and in sensitization to
      different DNA-damaging agents (MNNG, cisDDP, BLM and geneticin (G418). The pR
      sensitizing effect is specific to mammalian cells, since the plasmid can only
      protect prokaryotic cells against the damaging agents tested. The pR protecting
      effect requires the expression of both the uvp1 and uvp2 (mucAB) regions in
      bacteria as well as in mouse cells. The coordinated function of these regions
      could result in protection against typical SOS inducers through an SOS/SOS-like
      pathway. The sensitization conferred by pR plasmid depends mostly on the
      expression of the mucAB genes, as shown by the survival of mouse cells
      transfected with different pR::Tn5 mutants. In particular, BLM and G418 survival
      data demonstrate that, inserted into the pR plasmid, the ble and neo genes of the
      Tn5 transposon express themselves. This was confirmed by the presence of Tn5
      transcripts in untreated mouse cells. The comparison between the pR effects in
      bacterial and mouse cells shows that during evolution the repair pathways against
      UV damage are better conserved than those against other kinds of damage.

PMID- 7519735
TI  - Chromatid aberration dose responses and dispersal in human G2 lymphocytes treated
      with bleomycin: comparison with equivalent X-irradiation reveals formation of a
      novel class of heavily damaged cells.
AB  - We describe the dose responses and dispersal of chromatid (ct) aberrations in
      human peripheral blood lymphocytes, treated with a 5-min pulse of bleomycin (BLM)
      in doses ranging from 0.78 to 200 micrograms/ml during the G2 phase of the cell
      cycle. Damage was assessed in cells fixed at the time of peak damage 1 h after
      treatment. Both ct breaks and the percentages of damaged cells rose according to
      log BLM dose above 6.3 micrograms/ml only. Below this dose all endpoints
      exhibited flat responses suggestive of thresholding. A dose of 100 micrograms/ml
      produced similar amounts and distribution of ct breakage per cell (B/c) as a
      previously studied X-ray dose of 0.8 Gy, permitting future direct cytogenetic
      comparisons between clastogens. Within the scorable range (0-29 B/c) the
      dispersal of ct breakage after BLM treatment resembled that after equivalent X
      irradiation; but BLM treatment alone resulted in the formation of heavily damaged
      cells (HDC) defined as with > or = 30 B/c, representing a cytogenetic endpoint of
      DNA damage reminiscent of apoptosis. At the dose producing equivalent chromatid
      breakage, BLM produced 7.4 times fewer exchanges than X-rays in G2.

PMID- 7519734
TI  - Frequent involvement of visible chromosomal deletion in X-ray-induced mutants at
      the HLA-A locus in human T-lymphocytes.
AB  - Mutant T-lymphocytes at the HLA-A locus were isolated using a recently developed
      flow-cytometric assay either immediately after drawing blood (in vivo mutants) or
      after X-irradiation in vitro. Mutants were subsequently propagated clonally for
      cytogenetic and molecular analyses. Among the 38 in vivo mutants, none contained
      an abnormal chromosome 6 on which the HLA-A locus resides (6p21.3). In contrast,
      mutants recovered after in vitro irradiation frequently carried abnormalities in
      the short arm of chromosome 6: 11/19 and 5/5 independent mutants for the 1-Gy and
      2-Gy groups, respectively. Characteristically, the majority of the aberrations
      were deletions, commonly involving chromosome 6p21-p23. Because chromosomal
      deletions involving the selected gene are rare among radiation-induced mutants at
      the hypoxanthine phosphoribosyltransferase (chromosome X) and thymidine kinase
      (chromosome 17) loci, the HLA-A locus can be considered as highly prone to
      chromosomal deletions after radiation exposure. It is generally believed that
      ionizing radiation randomly breaks DNA, and the higher frequency of chromosomal
      deletions at the HLA-A locus is unlikely to be due to preferential induction but
      more likely to the better survivability of the deletion-bearing mutants.
      Consequently, the results suggest that the human genome is quite heterogeneous
      with regard to the survivability of cells bearing a chromosomal deletion
      including different loci.

PMID- 7519736
TI  - Radiosensitive target in the early mouse embryo exposed to very low doses of
      ionizing radiation.
AB  - We exposed mouse preimplantation embryos in vitro to either tritiated water (HTO)
      or tritiated thymidine (TdR) to determine whether the radiosensitive target was
      nuclear or extranuclear for embryonic cell proliferation disadvantage in the
      mouse embryo chimera assay. 8-cell embryos were incubated in either HTO or TdR
      for 2 h and paired with non-irradiated control embryos to form chimeras. Chimeras
      were cultured for an average of 20.2 h to allow for 2-3 cell cycles and then
      partially dissociated to obtain the number of progeny cells contributed by the
      two partner embryos for each chimera. These values were expressed as a
      "proliferation ratio" (number of cells from the irradiated embryo: total number
      of cells in the chimera). A ratio significantly less than 0.50 indicates that the
      experimental embryo expressed an embryonic cell proliferation disadvantage, which
      is the endpoint of this assay. The activity concentrations of HTO and TdR were
      adjusted so that both would deliver comparable mean absorbed nuclear doses during
      the combined initial 2-h irradiation incubation and subsequent 20.2 h chimera
      incubation periods. Although nuclear doses were comparable under these
      conditions, the extranuclear dose delivered by the uniformly distributed HTO was
      about 100 times greater than the extranuclear dose delivered by TdR for each
      given nuclear dose. Consequently, obtaining mean TdR proliferation ratios < or =
      mean HTO proliferation ratios would be evidence for a nuclear target while
      obtaining mean HTO proliferation ratios < mean TdR proliferation ratios would be
      evidence for an extranuclear target. TdR consistently produced lower mean
      proliferation ratios over a range of doses from 0.14 Gy to 0.43 Gy. Therefore, we
      conclude that the radiosensitive target for this endpoint is nuclear.

PMID- 7519737
TI  - Micronuclei and mitotic index in B-, T4- and T8-cells treated with mitomycin C
      and gamma-irradiation.
AB  - Lymphocytes were treated in vitro with mitomycin C and gamma-radiation at
      different doses (0-250 nmol/l and 0-2 Gy, respectively). After incubation in RPMI
      1640 medium and stimulation with phytohemagglutinin for 72 h, the lymphocyte
      subgroups T4 (CD4), T8 (CD8) and B (CD19) were separated by an immunomagnetic
      method and analyzed for the presence of micronuclei. With mitomycin C the highest
      levels were found in T4- and B-cells. When micronuclei were induced by
      irradiation the T4-cells showed the highest frequencies and the B-cells the
      lowest. The outcome of B-cells with gamma-irradiation was probably due to a
      pronounced cytotoxic reaction in this cell type, which could be measured as a
      decrease in mitotic index.

PMID- 7519738
TI  - Genetic effects of testicular incorporation of 137Cs in mice.
AB  - A comparative estimation of the frequencies of genetic disorders induced in germ
      cells of male mice by a single or long-term exposure to incorporated 137Cs or to
      external gamma-radiation has been carried out. The frequencies of dominant lethal
      mutations induced by a single exposure were similar with both types of radiation.
      In stem cell spermatogonia the frequency of reciprocal translocations was
      significantly lower in the case of single 137Cs administration than upon external
      gamma-radiation. Upon long-term administration the genetic efficiencies of both
      types of radiation were similar.

PMID- 7519739
TI  - Metabolic activation of a cigarette smoke condensate by woodchuck liver, as
      related to sex, pregnancy, hepatitis virus infection and primary hepatocellular
      carcinoma.
AB  - The liver S12 fractions from 23 woodchucks were assayed for the ability to
      activate a cigarette smoke condensate to metabolites inducing frameshift
      mutations in strain TA98 of S. typhimurium. At equivalent protein concentration,
      all samples activated this complex mixture to a similar extent, without any
      significant difference related to sex, hepatitis virus (WHV) infection, or
      primary hepatocellular carcinoma. Thus, unlike aflatoxin B1, aromatic amines and
      heterocyclic amines, whose metabolic activation has been shown to be stimulated
      by WHV infection in the same liver samples used in the present study, genotoxic
      components present in the particulate of mainstream cigarette smoke do not appear
      to be more readily biotransformed in vitro by preparations of infected
      hepatocytes. A significant increase of metabolism was however recorded in a small
      number of WHV-infected pregnant animals, which deserves attention in the light of
      the adverse effects of both hepadnavirus infection and cigarette smoking in
      pregnancy.

PMID- 7519741
TI  - A high frequency of induction of chromosome aberrations in the bone marrow cells
      of LEC strain rats by X-irradiation.
AB  - LEC strain rats, which have been known to develop hereditarily spontaneous
      fulminant hepatitis 4 to 5 months after birth, are highly sensitive to whole-body
      X-irradiation when compared to WKAH strain rats. The present results showed that
      the frequencies of all types of chromosome aberrations induced by X-irradiation
      in the bone marrow cells of LEC rats were approximately 2- to 3-fold higher than
      those of WKAH rats, though no significant difference was observed in the
      frequency of spontaneous chromosome aberrations between LEC and WKAH rats.

PMID- 7519740
TI  - Analysis of cells harboring a putative DNA repair gene reveals a lack of evidence
      for a second independent xeroderma pigmentosum group A correcting gene.
AB  - The UV hypersensitivity of xeroderma pigmentosum (XP) complementation group A
      cells is restored to near-normal by transfection of the XPA gene located on human
      chromosome 9. However, it has been reported that a cosmid related to a cDNA on
      chromosome 8 is also able to partially correct the UV sensitivity of XP-A cells.
      We describe here an investigation of a representative cosmid transfectant,
      denoted 2-0-A2. Whole cell extracts prepared from 2-0-A2 cells carried out DNA
      repair synthesis in vitro that was in the normal range, consistent with their UV
      resistant phenotype. Immunoblotting indicated that 2-0-A2 cells expressed full
      length XPA protein. This was unexpected because the 2-0-A2 cell line was thought
      to have been isolated by transfection of a cell line derived from patient XP2OS,
      and a known homozygous mutation in XP2OS prevents expression of XPA gene product.
      This mutation creates an AlwNI restriction endonuclease cleavage site in XPA and
      was not present in 2-0-A2. These results prompted an RFLP analysis which revealed
      that the 2-0-A2 cell line was not derived from XP2OS but from another line that
      fails to express XPA protein, XP12BE. It appears that the significant UV
      resistance and DNA repair capacity of 2-0-A2 can be ascribed to the re-expression
      of XPA in XP12BE, and it is unnecessary to postulate a second XP-A complementing
      gene to explain the results.

PMID- 7519743
TI  - Variability of the composition of chlorophyllin.

PMID- 7519742
TI  - Mutagenesis in mammalian cells can be modulated by radiation-induced voltage
      dependent potassium channels.
AB  - In mammalian cells, little is known about the initial events whose ultimate
      consequence is mutagenesis or DNA repair. The role the plasma membrane may play
      as an initiator of such a pathway is not understood. We show, for the first time,
      that membrane voltage-dependent potassium (K+) currents, activated by ionizing
      radiation (Kuo et al., 1993), play a significant role in radiation mutagenesis.
      Specifically, we show that the frequency of mutation at the HGPRT locus is
      increased as expected to 37.6 +/- 4.0 mutations per 100,000 survivors by 800 cGy
      of ionizing radiation from a spontaneous frequency of 1.5 +/- 1.5. This increase,
      however, is abolished if either K+ channel blocker, CsCl or BaCl2, is present for
      2 h following irradiation of the cells. RbCl, chemically similar to CsCl but
      known not to block K+ channels, is ineffective in reducing the mutation
      frequency. Treatment of cells with CsCl or BaCl2 had no effect on radiation
      induced cell killing.

PMID- 7519744
TI  - Triple-marker screening of serum for Down's syndrome.

PMID- 7519746
TI  - Proliferating cell nuclear antigen expression in rat glioma model: comparison
      with bromodeoxyuridine labeling index.
AB  - The usefulness of proliferating cell nuclear antigen (PCNA) immunostaining for
      estimating the growth fraction in glial tumors was evaluated in ethylnitrosourea
      induced rat gliomas. The PCNA labeling index was compared with the
      bromodeoxyuridine (BrdU) labeling index, using alternate serial sections fixed
      either in 10% formalin or in periodonate-lysine-paraformaldehyde (PLP). The PCNA
      labeling index was significantly correlated with the BrdU labeling index if cells
      with only faint PCNA staining were excluded. Differences in PCNA staining were
      noted between the two fixatives. The number of PCNA-positive cells in PLP-fixed
      material was greater than in 10% formalin-fixed material, but showed a poorer
      correlation with BrdU labeling index. Over-fixation in formalin reduced the
      number of positive cells. Although peritumoral tissue did not exhibit
      overexpression of PCNA, the ependymal lining was weakly stained even in areas
      distant from the tumor. PCNA labeling index is a useful method to estimate the
      growth fraction when the materials are processed in a controlled way. When
      clinical specimens with uncertain preparation are used, care is required in
      interpreting the results.

PMID- 7519745
TI  - More poison from Agatha Christie.

PMID- 7519747
TI  - Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma
      cells linked with cell cycle arrest in G1 phase.
AB  - The effects of tumor necrosis factor-alpha (TNF) on proliferation and cell cycle
      alterations in human malignant glioma cell lines, SF-188 and LN-382, were
      investigated by flow cytometry with the bromodeoxyuridine-propidium iodide dual
      staining technique. Low concentrations of TNF (1-100 U/ml) suppressed the growth
      of SF-188 assessed by cell count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay, and thymidine incorporation assay, but not that of LN
      382. After TNF treatment, the percentage of SF-188 cells in the G0/G1 phase
      increased, while the percentage of cells in the S phase decreased. LN-382 cells
      did not show any marked change in cell kinetics. TNF arrests certain human glioma
      cells in the G0/G1 phase resulting in reduction of deoxyribonucleic acid
      synthesis in the subsequent S phase, suppressing the proliferation pathway.

PMID- 7519748
TI  - Human monoclonal antibody-drug conjugates in the experimental treatment of
      malignant gliomas--studies in vitro and in vivo.
AB  - The chemotherapeutic agents doxorubicin (DXR) and 4'-epi-doxorubicin were
      separately conjugated to the human monoclonal antibody CLNIgG, which binds
      strongly to human malignant glioma cells. The antibody-drug conjugates were more
      potent than the free drugs in killing human glioma cells in vitro and in vivo
      (subcutaneous glioma model). A biodistribution study using [14-14C]DXR-CLNIgG
      conjugate indicated that immunoconjugates delivered at least five times more DXR
      to glioma tissues than free DXR alone in nude mice without increasing the
      concentration in other tissues. In a nude rat intracerebral glioma model,
      intracarotid hyperosmolar perfusion to achieve blood-brain barrier (BBB) opening
      caused a 640% increase in the DXR-CLNIgG concentration in intracerebral tumor
      tissue. Human monoclonal antibody-drug conjugates in combination with BBB opening
      is a potential new approach to the treatment of malignant gliomas.

PMID- 7519749
TI  - Incidental white matter lesions identified on magnetic resonance images of normal
      Japanese individuals--correlation with age and hypertension.
AB  - Incidental white matter high-intensity lesions are frequently seen on T2-weighted
      magnetic resonance (MR) images of the brain in older people. The incidence
      increases with advancing age or hypertension. Brain MR images of 59 normal
      individuals were examined to analyze this phenomenon. The total number of white
      matter high-intensity lesions correlated significantly with age (p = 0.004) or
      systolic blood pressure (p = 0.03). The 60- to 69-year-old group demonstrated a
      very close correlation of white matter lesions with systolic (p = 0.02) and
      diastolic blood pressure (p = 0.01), in contrast to the 50- to 59-year-old group.
      Hypertensive subjects in their 60s are thought to develop more white matter
      lesions than subjects in their 50s.

PMID- 7519751
TI  - Extra-axial ependymoma--case report.
AB  - A 13-year-old boy presented with a very unusual ependymoma extending extra
      axially. Computed tomography demonstrated a tumor with a cyst and calcification
      adjacent to the dura and extending over the right occipital and parietal lobes.
      The cyst wall and solid tumor were enhanced postcontrast. Magnetic resonance
      imaging revealed that the solid tumor was isointense on T1-weighted images and a
      mixed iso- and high-intensity on T2-weighted images. The solid tumor and tissue
      surrounding the cyst were enhanced markedly by gadolinium
      diethylenetriaminepentaacetic acid. Sagittal and coronal images demonstrated a
      multilocular tumor shadow. Cerebral angiography demonstrated a tumor fed by a
      posterior branch of the right middle meningeal artery but no feeders from the
      internal carotid and vertebral arteries. The tumor was removed en bloc. The
      histological diagnosis was clear cell-type ependymoma.

PMID- 7519750
TI  - Germinoma of the medulla oblongata--case report.
AB  - A 32-year-old female presented with medulla oblongata germinoma manifesting as
      numbness in the extremities. Computed tomography demonstrated a mass in the
      medulla oblongata expanding into the fourth ventricle. The tumor was partially
      removed. Immunohistochemical staining of the tumor specimen demonstrated large
      epithelioid cells positive for placental alkaline phosphatase, and
      syncytiotrophoblastic cells positive for beta subunit of human chorionic
      gonadotropin. Some epithelioid cells were also positive for cytokeratin. She
      received 44 Gy of irradiation to the posterior fossa and 20 Gy whole spinal
      irradiation. No signs of recurrence have occurred for 9 years. Patients with
      medulla oblongata germ cell tumor are comparatively older than those with other
      intracranial germ cell tumors and have two X chromosomes. All tumors were
      diagnosed as germinoma, and caused symptoms of involvement of the lower cranial
      nerves and the lower brain stem without pyramidal tract signs.

PMID- 7519752
TI  - Dural arteriovenous malformation involving the inferior petrosal sinus--case
      report.
AB  - A 59-year-old male presented with a dural arteriovenous malformation involving
      the inferior petrosal sinus manifesting as false-localizing ocular symptoms.
      Occlusion between the right inferior petrosal sinus and the right jugular bulb
      caused an unusual retrograde venous outflow from the inferior petrosal sinus to
      the cavernous sinus, thought to have been responsible for the chemosis, abducens
      nerve paresis, and orbital bruit. He was treated successfully with transarterial
      embolization and radiotherapy.

PMID- 7519753
TI  - Concurrent subarachnoid hemorrhage due to ruptured aneurysm and hypertensive
      intracerebral hemorrhage--case report.
AB  - A 64-year-old female presented with hypertensive thalamic hemorrhage concurrent
      with subarachnoid hemorrhage (SAH) due to a ruptured aneurysm manifesting as
      sudden onset of right hemiparesis followed by severe headache. The aneurysm was
      located in the basilar artery at the origin of the superior cerebellar artery,
      remote from the thalamic hematoma. The aneurysm was clipped 3 weeks after SAH.
      She was discharged with slight right hemiparesis. The method and timing of
      surgery for such patients depend on hematoma size, location of the aneurysm and
      hematoma, and neurological status. The intracerebral hemorrhage remote from the
      ruptured aneurysm should be treated initially if necessary, and the aneurysm
      clipped after the brain swelling has reduced.

PMID- 7519754
TI  - Dissecting aneurysm in the proximal region of the posterior inferior cerebellar
      artery presenting as Wallenberg's syndrome--case report.
AB  - A 29-year-old female presented with an unusual case of Wallenberg's syndrome due
      to a dissecting aneurysm of the posterior inferior cerebellar artery (PICA)
      manifesting as a sensation of heaviness in the occipital region and vertigo.
      Magnetic resonance imaging revealed infarction of the lateral aspect of the
      medulla oblongata. Digital subtraction angiography (DSA) revealed a spindle
      shaped dilatation of irregular contour in the proximal portion of the left PICA.
      Pooling of contrast medium was noted in the venous phase but not double lumen
      sign. A suboccipital craniectomy confirmed these findings macroscopically. Blood
      flow meter monitoring before and after proximal clipping of the diseased vessel
      ensured the safety of the procedure. Follow-up DSA 3 years after surgery revealed
      no evidence of aneurysm recurrence.

PMID- 7519755
TI  - Giant thrombosed vertebral artery aneurysm treated by extracranial-intracranial
      bypass and aneurysmectomy--case report.
AB  - A 42-year-old male presented with a giant thrombosed aneurysm of the left
      vertebral artery. The aneurysm was resected through a combined subtemporal and
      suboccipital approach after a saphenous vein bypass graft was placed between the
      right external carotid artery and the posterior cerebral artery. Intraoperative
      measurements of the blood flow volume and pressure demonstrated good blood flow
      in the bypass. Postoperatively, uncontrollable hypertension resulted in huge
      intracerebral hematoma formation and increased intracranial pressure. Control of
      systemic hypertension is essential in such patients.

PMID- 7519756
TI  - Postoperative fungal arteritis mimicking vasospasm--case report.
AB  - Intracranial arteritis due to fungal infection is an uncommon complication of
      neurosurgical operations. A 36-year-old female developed arteritis caused by
      Aspergillus fumigatus at the site of the temporary clip following the clipping of
      an initially uncomplicated intracranial aneurysm. The inflammatory, slowly
      progressing vascular occlusion mimicked the vasospasm common in subarachnoid
      hemorrhage.

PMID- 7519759
TI  - Localization and actions of nitric oxide in the cat carotid body.
AB  - An extensive plexus of nerve fibers capable of synthesizing nitric oxide was
      demonstrated in the cat carotid body by immunocytochemical and biochemical
      studies of nitric oxide synthase. Denervation experiments indicated that the
      axons originate from: (i) microganglial neurons located within the carotid body
      and along the glossopharyngeal and carotid sinus nerves, whose ramifications
      primarily innervate carotid body blood vessels; and (ii), sensory neurons in the
      petrosal ganglion, whose terminals end in association with lobules of type I
      cells. In the in vitro superfused cat carotid body, the nitric oxide synthase
      substrate, L-arginine, induced a dose-dependent inhibition of carotid sinus nerve
      discharge evoked by hypoxia. In contrast, the nitric oxide synthase inhibitor, L
      NG-nitroarginine methylester, augmented the chemoreceptor response to hypoxia,
      and this effect was markedly enhanced when the preparation was both perfused and
      superfused in vitro. The nitric oxide donor, nitroglycerine, inhibited carotid
      sinus nerve discharge, and immunocytochemistry revealed that this drug stimulated
      the formation of cyclic 3',5'-guanosine monophosphate in both type I cells and
      blood vessels. Our data indicate that nitric oxide is an inhibitory neuronal
      messenger in the carotid body, which affects the process of chemoreceptor
      transduction/transmission via actions on both the receptor elements and their
      associated blood vessels.

PMID- 7519760
TI  - The brain protein S-100ab induces apoptosis in PC12 cells.
AB  - Incubation of PC12 cells with S-100 protein induces a rapid (0.5-1.0 min) rise of
      intracellular Ca2+ which lasts for the whole period of incubation. This effect is
      abolished in a Ca(2+)-free medium or in the presence of 1.0 microM Ni2+, an
      inhibitor of calcium channels. The rise in intracellular Ca2+ is followed by a
      progressive increase of cells undergoing degeneration and death. This event is
      accompanied by the appearance of apoptotic bodies and DNA fragmentation typical
      of the process known as apoptosis. S-100-induced cell death is prevented by 1
      microM Ni2+ or by 0.1 nM cycloheximide, suggesting the involvement of new protein
      synthesis. It is postulated that the binding of S-100ab to specific sites present
      in PC12 cells is followed by the formation of Ca2+ channels and/or the
      stimulation of pre-existing ones with consequent increase of Ca2+ influx and
      activation of a process of cell death.

PMID- 7519761
TI  - Immunohistochemical localization in the rat brain of an epitope corresponding to
      the fibroblast growth factor receptor-1.
AB  - The localization of fibroblast growth factor receptor-1 was investigated in rat
      brain by immunohistochemistry using a polyclonal antibody against an acidic
      peptide sequence of chicken fibroblast growth factor receptor-1. For raising the
      antisera in rabbits, we synthesized the oligopeptide EDDDDEDDSSSEEKEAD which is a
      highly acidic region of chicken fibroblast growth factor receptor-1. The
      oligopeptide was used as a haptenic antigen by conjugating with poly-L-glutamate
      as a carrier protein. On immunospot assay, the best antiserum was capable of
      detecting 15.7 pmols of both the chicken and its analogous human oligopeptides
      but failed to react even with up to 1 nmol of poly-L-glutamate. When rat brain
      homogenate was examined by Western blots, the antiserum revealed two bands with
      molecular weights of 145,000 and 75,000 corresponding to known sizes of the
      membrane-bound and secreted forms of the rat receptor, respectively.
      Immunohistochemistry in rat brain demonstrated that putative fibroblast growth
      factor receptor-1 immunoreactivity sites were present mainly in neurons but also
      in tanycytes and ependymal cells. Positive neurons were distributed widely in
      various brain regions, but were particularly abundant in such regions as the
      lateral hypothalamus, substantia nigra, locus coeruleus and raphe nuclei. The
      present study suggests that fibroblast growth factor receptor-1 is expressed
      preferentially in certain neuronal systems that appear to be under the influence
      of fibroblast growth factors in the normal brain. The result should facilitate
      study of the functional significance of fibroblast growth factors in these brain
      neurons.

PMID- 7519757
TI  - Myelin basic protein in the cerebrospinal fluid of patients with brain tumors.
AB  - We measured the level of myelin basic protein (MBP) in the cerebrospinal fluid
      (CSF) of patients with various kinds of tumors, including malignant tumors, using
      radioimmunoassay. The CSF had been obtained by lumbar puncture through an Ommaya
      reservoir or a shunt device placed in the lateral ventricle. The level of MBP was
      high (> 4 ng/ml) in the patients with meningeal dissemination of malignant
      tumors, but in those who showed a good response to chemotherapy and/or radiation,
      it decreased or returned to the normal level, with improvement on the computed
      tomography and magnetic resonance imaging, cytological, general CSF, and
      neurological findings. Of seven malignant gliomas without CSF dissemination, six
      showed an elevated level of MBP before selective intra-arterial chemotherapy with
      a combination of etoposide and cisplatin administered via a microcatheter placed
      at A1, M1, P1-P2, and the basilar top. All CSF specimens obtained during the
      period of the intra-arterial chemotherapy showed an abnormally high (> 4 ng/ml)
      level of MBP that exceeded the prechemotherapy level. The MBP level decreased or
      returned to normal in the patients with a good response to chemotherapy after
      intra-arterial chemotherapy. In some patients with multiple metastatic brain
      tumors, the MBP level was elevated before treatment and returned to normal after
      treatment (surgical removal, chemotherapy, and/or irradiation) in all except one.
      Thus, there was a clear correlation between the timing of treatment and changes
      in imaging studies and MBP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519762
TI  - Hepatitis C virus infection in renal dialysis patients in Glasgow.
AB  - A survey of all 483 adult dialysis patients in the three renal units in Glasgow
      using second-generation ELISA was carried out to determine hepatitis C virus
      (HCV) seroprevalence in the summer of 1991 before the introduction of blood donor
      screening for antibody to HCV in the UK. Supplementary testing of ELISA positive
      sera was by second-generation immunoblot assay (RIBA-2, Chiron). Retrospective
      case note analysis and testing of stored sera were performed to assess liver
      function and the risk factors for acquisition of the virus. Nineteen of the 483
      patients (3.9%) were seropositive. Sixteen patients had been transfused and 12
      had previous transplants. Seropositivity was associated with current
      haemodialysis (P < 0.01) rather than continuous ambulatory peritoneal dialysis
      (CAPD). Of those on haemodialysis, the time since first dialysis was longer for
      seropositives (13.6 years) than for seronegatives (6.3 years) (P < 0.01) but this
      did not apply to those on CAPD. Twelve of 19 (63.2%) seropositives had persistent
      elevations of alanine transferase compared to seven of 38 (18%) seronegative
      controls (P < 0.01). This large group of dialysis patients is at special risk of
      HCV infection but the seroprevalence is less than that reported from outside the
      UK despite the use of more sensitive techniques. The risk is associated with
      haemodialysis and is probably largely due to blood transfusion. The introduction
      of screening of donated blood for HCV antibody should reduce the incidence of new
      infection in dialysis patients.

PMID- 7519763
TI  - Optimal method for RNA extraction from mouse glomeruli.
AB  - Extraction of RNA has been described for rat and rabbit glomeruli but not for
      mouse glomeruli. Due to their small size, mouse glomeruli cannot be isolated by
      relatively simple sieving techniques. Based on recently reported methods for the
      isolation of mouse glomeruli, we developed an RNA isolation technique by
      performing comparative methodological studies. Two standard RNA extraction
      methods were compared. In addition in separate experiments the influence was
      studied of protease inhibitors and freezing and thawing of whole kidney prior to
      glomeruli isolation, on the yield and degradation of RNA. Therefore kidneys were
      perfused with 10 ml 0.01 M PBS containing 1.25% Fe3O4 through the aorta. Kidneys
      were decapsulated and passed through a 75-microns metal screen. After pelletting
      and washing, tubes were placed against a magnet and pelleted glomeruli were
      washed three times. In a second experiment protease inhibitors were added to the
      PBS. As a third method, kidneys were frozen before the isolation of glomeruli.
      From isolated glomeruli RNA was extracted using either caesium chloride or
      lithium chloride method. The yields of RNA (OD 260) were highest using the
      lithium chloride method. Hybridization of Northern blots of extracted RNA with
      cDNA probes showed the best results when RNA was extracted using the lithium
      chloride method, while the caesium chloride method led to considerable
      degradation of RNA. Freezing of kidney tissue prior to RNA extraction led to the
      virtual absence of any signal. We then applied this method successfully in an in
      vivo model of experimental lupus nephritis. This is the first description of an
      optimal protocol for the extraction of RNA from mouse glomeruli.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7519758
TI  - Galanin expression increases in adult rat sympathetic neurons after axotomy.
AB  - Changes in neuropeptide expression occur in sensory, motor, and sympathetic
      neurons following axotomy. The particular pattern of peptide changes that occurs
      varies among the three cell types. We have studied the regulation in the rat
      superior cervical ganglion of the expression of galanin, a peptide previously
      shown to increase in axotomized sensory and motor neurons. While normally only an
      occasional neuron exhibiting galanin-like immunoreactivity is found in this
      ganglion, at two days after transection of the postganglionic internal and
      external carotid nerves, immunostaining can be observed in many neurons
      throughout the ganglion. Similar changes are found when ganglia are placed in
      organ culture for two days. The distribution of immunostained neurons after
      section of only one of the postganglionic trunks suggests that changes in galanin
      like immunoreactivity occur only within neurons whose axons are transected. None
      the less, even when both nerve trunks are transected, only about half of the
      neurons in the ganglion exhibit galanin-like immunoreactivity, indicating that
      only a proportion of the axotomized neurons exhibit a detectable response. The
      few immunostained neurons seen after section of the cervical sympathetic trunk
      may also represent axotomized neurons. Galanin-like immunoreactivity extracted
      from the ganglion co-chromatographs with authentic galanin, and the level of this
      immunoreactivity increases dramatically after axotomy and explantation, and
      modestly after decentralization. These same manipulations produce parallel
      increases in the level of galanin messenger RNA. Together, the findings indicate
      that the expression of galanin increases in sympathetic neurons after axotomy.
      Galanin is thus the first neuropeptide whose expression has been shown to
      increase after transection of all three types of peripheral axons that have been
      studied.

PMID- 7519764
TI  - [Endocrine effect of a new anti-estrogen compound (EGIS-5650, panomifene) in
      healthy volunteers: phase I/a study].
AB  - Influence of a new Hungarian antiestrogen, panomifene (PAN) was investigated on
      some hormone levels of 10 postmenopausal healthy women during a partially double
      blind placebo controlled phase I/a study. Following a single oral administration
      of PAN serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing
      hormone (LH) and prolactin (PROL) levels were measured by RIA at two selected
      dose levels: 12 mg and 120 mg. The low dose (12 mg) results in an increased E2
      level in some cases probably due to the intrinsic estrogenic (agonistic)
      character of the drug. The high dose (120 mg) seems to have a strong
      antiestrogenic (antagonistic) action. FSH and LH changed within the normal
      postmenopausal range at both doses, PROL slightly decreased at 12 mg dose level.
      During the 14-day follow up, the 120 mg PAN considerably suppressed the PROL
      secretion proving the antiestrogenic character of the "high" dose. PAN seems to
      be a safe tamoxifen analogue, the single oral dose of which does not exert any
      noteworthy (pathogenic) side effect on some hormone levels of healthy women.

PMID- 7519765
TI  - [The role of Nd-YAG in the management of tracheobronchial stenosis].
AB  - 122 patients with the main airway stenosis were treated with Nd-YAG laser
      phototherapy. The endobronchial laser treatment was performed either with
      flexible bronchoscope (64%), or with rigid instrument (36%). This method can
      result a final recovery of the patients with benign tumors, or inflammatory
      processes, at the patients with malignant tumors can be achieved an effective
      palliation. Taking account the generally accepted indications and
      contraindications of the endobronchial laser phototherapy the number of the
      complications can be reduced.

PMID- 7519766
TI  - Characterization of Ca(2+)-activated K+ channels in excised patches of human T
      lymphocytes.
AB  - Ca(2+)-activated K+ [K(Ca)] channels were studied in excised patches of resting
      and activated human peripheral blood T lymphocytes. The K(Ca) channel had a
      single-channel conductance of 50 +/- 6 pS in symmetrical high-K+ solutions in the
      potential range of -100 to -10 mV and was inwardly rectifying at more depolarized
      potentials. The channel was sensitive to block by charybdotoxin (10 nM) and
      insensitive to apamin (3 nM). Half-maximum activation occurred at an internal
      free Ca2+ concentration of 360 +/- 110 nM. The concentration-effect curve had a
      slope factor of 0.83 +/- 0.12, suggesting a 1:1 interaction of Ca2+ ions with the
      channel. Ca2+ affects the open time probability of the K(Ca) channels, mainly by
      modulating the frequency of channel opening. The open probability did not show
      voltage dependence. The kinetics of the channel could be described assuming one
      open state and two closed states. The time constant of the exponential describing
      the open time distribution amounted to 2.8 +/- 1.2 ms, whereas the closed time
      distribution could be described with two exponentials with time constants of 0.2
      +/- 0.05 ms and 8.0 +/- 2.1 ms, respectively. Resting T lymphocytes expressed a
      low number of channels but the density of channels increased dramatically during
      chronic phytohaemagglutinin stimulation.

PMID- 7519767
TI  - Formation of sheared G:A base pairs in an RNA duplex modelled after ribozymes, as
      revealed by NMR.
AB  - The thermal stability and structure of an RNA duplex, r(GGACGAGUCC)2, the base
      sequence of which was modelled after both a hammerhead ribozyme and a lead
      ribozyme, were studied by CD and NMR. We previously demonstrated that the
      corresponding DNA duplex, d(GGACGAGTCC)2, formed unique 'sheared' G:A base pairs,
      where an amino proton, instead of an imino proton, of G is involved in the
      hydrogen bonding, and G and A bases are arranged 'side by side' instead of 'head
      to head' (Nucleic Acids Res. (1993) 21, 5418-5424). CD melting profiles showed
      that the RNA duplex is thermally more stable than the corresponding DNA duplex.
      NMR studies revealed that sheared G:A base pairs are formed in the RNA duplex,
      too, although the overall structure of the RNA is the A form, which differs from
      the B form taken on by the corresponding DNA. A model building study confirmed
      that sheared G:A base pairs can be accommodated in the double helical structure
      of the A form. A difference between the RNA and DNA duplexes in the stacking
      interaction involving G:A mismatch bases is also suggested. The demonstration
      that sheared G:A base pairs can be formed not only in DNA but also in RNA
      suggests that this base pairing plays an important role regarding the RNA
      structure.

PMID- 7519769
TI  - The application of a modified nucleotide in aptamer selection: novel thrombin
      aptamers containing 5-(1-pentynyl)-2'-deoxyuridine.
AB  - Combinatorial libraries of nucleic acids are developing into novel sources for
      lead compounds in drug development. In order to diversify the pool of ss DNA
      sequences, we have used a modified nucleotide, 5-(1-pentynyl)-2'-deoxyuridine, in
      place of thymidine in a random nucleic acid library and screened this library
      against human thrombin. Previously, we described this screening method to
      identify a novel structural inhibitor (an aptamer) of the coagulation protease
      thrombin (Bock, L. et. al. (1992) Nature 355 564-566). Using the modified nucleic
      acid library, we have now isolated a second pool of thrombin inhibitors with
      strikingly different sequence composition compared to the selection using natural
      bases. This second class of aptamers is dependent on the presence of the modified
      nucleotide for protein binding and clotting inhibition. Our method represents a
      potential strategy to enhance the diversity of libraries for in vitro selection,
      and thereby increasing the utility of this technique in the identification of
      molecules with novel biochemical properties.

PMID- 7519771
TI  - Taq DNA polymerase extension of internal primers blocks polymerase chain
      reactions allowing differential amplification of molecules with identical 5' and
      3' ends.

PMID- 7519770
TI  - Different conformational families of pyrimidine.purine.pyrimidine triple helices
      depending on backbone composition.
AB  - Different helical conformations of DNA (D), RNA (R), and DNA.RNA (DR) hybrid
      double and triple helices have been detected using affinity cleavage analysis.
      Synthetic methods were developed to attach EDTA.Fe to a single nucleotide on RNA
      as well as DNA oligonucleotides. Cleavage patterns generated by a localized
      diffusible oxidant in the major groove on the pyrimidine strand of four
      purine.pyrimidine double helices consisting of all DNA, all RNA, and the
      corresponding hybrids reveal that the relative cleavage intensity shifts to the
      5' end of the purine strand increasingly in the order: DD < DR < RD < RR. These
      results are consistent with models derived from structural studies. In six
      pyrimidine.purine.pyrimidine triple helices, the altered cleavage patterns of the
      Watson-Crick pyrimidine strands reveal at least two conformational families: (i)
      D + DD, R + DD, D + DR, and R + DR and (ii) R + RD and R + RR.

PMID- 7519773
TI  - Maternal serum human chorionic gonadotrophin and pregnancy-associated plasma
      protein A, markers for fetal Down syndrome at 8-14 weeks.
AB  - Maternal serum levels of human chorionic gonadotrophin and its subunits (intact,
      alpha, and free beta h CG) and pregnancy-associated plasma protein A (PAPP-A)
      were measured in 279 women between 8 and 14 weeks' gestation. This group included
      23 pregnancies in which the fetus had Down syndrome (DS), diagnosed either at
      birth or during the second trimester (n = 17) or from chorionic villus sampling
      (CVS) (n = 6). Normal medians were determined from the 258 apparently normal
      pregnancies. The median levels of intact hCG (1.4 MOM) and free beta hCG (2.1
      MOM) were significantly raised, whereas the median level of PAPP-A (0.39 MOM) was
      significantly lower in the DS pregnancies when compared with the control group.
      Levels of alpha hCG were similar in both the control and the DS pregnancies.
      Analysis of samples taken prior to 14 weeks' gestation demonstrated that only
      PAPP-A (0.34 MOM) was significantly altered in DS pregnancies. However, after the
      exclusion of DS cases diagnosed at CVS, the median intact hCG (1.56 MOM), free
      beta hCG (2.27 MOM), and alpha hCG (1.8 MOM) were all raised in DS pregnancies.
      This emphasizes the problem of the interpretation of biochemical markers when DS
      cases are diagnosed at CVS.

PMID- 7519772
TI  - Isolation of DNA fragments from agarose gel by centrifugation.

PMID- 7519768
TI  - Polyadenylation and transcription termination in gene constructs containing
      multiple tandem polyadenylation signals.
AB  - The processes of pre-mRNA 3'-end cleavage and polyadenylation have been closely
      linked to transcription termination by RNA polymerase II. We have studied the
      relationship between polyadenylation and transcription termination in gene
      constructs containing tandem poly(A) signals, at least one of which is the
      inefficient polyomavirus late poly(A) site. When identical tandem viral signals
      were separated by fewer than 400 bp, they competed for polyadenylation. The
      upstream site was always chosen preferentially, but relative site choice was
      influenced by the distance between the signals. All of these constructs showed
      the same low level of transcription termination as wild type polyomavirus, which
      contains a single late poly(A) site. When tandem poly(A) signals were not
      identical, a stronger downstream signal could outcompete a weaker upstream signal
      for polyadenylation without altering the efficiency of transcription termination
      characteristic for use of the upstream signal. Thus, if a weak polyoma virus late
      poly(A) signal (associated with inefficient transcription termination) preceded a
      strong rabbit beta-globin signal (associated with efficient transcription
      termination), termination remained inefficient, but the distal signal was most
      often chosen for polyadenylation. These results are consistent with independent
      regulation of polyadenylation and transcription termination in this system and
      are discussed in light of current models for the dependence of transcription
      termination on a functional poly(A) site.

PMID- 7519774
TI  - [Expression and secretion of alpha-2-macroglobulin by dust-stimulated alveolar
      macrophages].
AB  - In dust-induced, fibrosing lung processes macrophages are increased activated by
      foreign body reactions. The release of monokines and proteolytic enzymes, which
      depends on phagocytosis, may lead to destruction of the extracellular matrix with
      the consequence of degradation and restitution. Also the transcellular signaling
      or cell-matrix-interaction may finally result in development of fibrosis. However
      the proteolytic effect of elastase and collagenase can be inhibited by alpha-2
      macroglobulin. Alpha-2-macroglobulin is a protease-inhibitor, which is
      synthesized by macrophages and has a wide spectrum of inhibitory abilities. Our
      interest was focused on observation of the production of alpha-2-macroglobulin by
      alveolar macrophages after stimulation with inorganic dusts of different chemical
      and physical properties. Rat alveolar macrophages were isolated by
      bronchoalveolar lavage and exposed to crocidolite, quarz or welder steam dust in
      vitro. The expression and secretion of alpha-2-macroglobulin was examined by non
      radioactive in situ hybridization, indirect immunofluorescence and radial
      immunodiffusion according to Mancini. The stimulated rat alveolar macrophages
      showed an increased expression of alpha-2-macroglobulin-mRNA and also an enhanced
      synthesis of alpha-2-macroglobulin-protein. Besides only small differences
      between the substances used for stimulation were demonstrated.

PMID- 7519776
TI  - Assembly of synthetic cellulose I.
AB  - Cellulose microfibrils with an electron diffraction pattern characteristic of
      crystalline native cellulose I have been assembled abiotically by means of a
      cellulase-catalyzed polymerization of beta-cellobiosyl fluoride substrate monomer
      in acetonitrile/acetate buffer. Substantial purification of the Trichoderma
      viride cellulase enzyme was found to be essential for the formation of the
      synthetic cellulose I allomorph. Assembly of synthetic cellulose I appears to be
      a result of a micellar aggregation of the partially purified enzyme and the
      substrate in an organic/aqueous solvent system favoring the alignment of glucan
      chains with the same polarity and extended chain conformation, resulting in
      crystallization to form the metastable cellulose I allomorph.

PMID- 7519777
TI  - Gene for an extracellular matrix receptor protein from Pneumocystis carinii.
AB  - An initial and crucial step in the establishment of many microbial infections is
      the attachment of the pathogen to the host cells. Thus, adherence of Pneumocystis
      carinii (Pc) to type I pneumocytes is believed to be important in the induction
      of Pc pneumonia. Little is known about the nature of the attachment of Pc to type
      I cells, although extracellular matrix (ECM) proteins, such as fibronectin and
      laminin, have been implicated in the process. We report here the isolation of a
      Pc gene encoding a receptor protein that binds both fibronectin and laminin in
      vitro. A cDNA clone encoding the Pc ECM receptor was isolated from a Pc cDNA
      library and identified on the basis of sequence homology to the human colon
      carcinoma laminin receptor. Southern blot analysis of Pc genomic DNA confirmed
      that the cDNA was of Pc origin. Northern blot analysis of Pc total RNA showed a
      predominant mRNA of approximately 1400 nucleotides that hybridized to the ECM
      receptor gene. The ECM receptor predicted from the cDNA sequence is 295 amino
      acid residues long, with a molecular mass of 32.8 kDa. The C-terminal third of
      the polypeptide is highly negatively charged, whereas the N-terminal two-thirds
      contains hydrophobic segments that may play a role in membrane association.
      Sequence analysis and alignment of the N terminus with the laminin receptor cDNA
      sequence of human colon carcinoma support the conclusion that the Pc ECM receptor
      cDNA clone is a full-length clone. A Western blot of the overexpressed ECM
      receptor protein bound both laminin and fibronectin in vitro. Antibodies raised
      to the overexpressed receptor protein interacted with a 33-kDa protein in total
      Pc cell lysates. These findings raise the possibility that the Pc ECM receptor
      protein may mediate the organism's attachment to type I pneumocytes and, thus,
      may play a crucial role in Pc pathogenesis.

PMID- 7519775
TI  - Selectin ligands.
AB  - The selectins initiate many critical interactions among blood cells. The volume
      of information and diversity of opinions on the nature of the biologically
      relevant ligands for selectins is remarkable. This review analyzes the matter and
      suggests the hypothesis that at least some of the specificity may involve
      recognition of "clustered saccharide patches."

PMID- 7519778
TI  - Nitric oxide as a mediator of oxidant lung injury due to paraquat.
AB  - At low concentrations, nitric oxide is a physiological transmitter, but in
      excessive concentrations it may cause cell and tissue injury. We report that in
      acute oxidant injury induced by the herbicide paraquat in isolated guinea pig
      lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased
      levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production
      in lung tissue. All signs of injury, including increased airway and perfusion
      pressures, pulmonary edema, and protein leakage into the airspaces, were dose
      dependently attenuated or totally prevented by either NG-nitro-L-arginine methyl
      ester or N omega-nitro-L-arginine, selective and competitive inhibitors of nitric
      oxide synthase. Protection was reversed by excess L-arginine but not by its
      enantiomer D-arginine. When blood was added to the lung perfusate, the paraquat
      injury was moderated or delayed as it was when paraquat was given to anesthetized
      guinea pigs. The rapid onset of injury and its failure to occur in the absence of
      Ca2+ suggest that constitutive rather than inducible nitric oxide synthase was
      responsible for the stimulated nitric oxide synthesis. The findings indicate that
      nitric oxide plays a critical role in the production of lung tissue injury due to
      paraquat, and it may be a pathogenetic factor in other forms of oxidant tissue
      injury.

PMID- 7519779
TI  - Interleukin 3 stimulates protein synthesis by regulating double-stranded RNA
      dependent protein kinase.
AB  - In a murine interleukin 3 (IL-3)-dependent cell line, IL-3 deprivation resulted
      in increased autophosphorylation of double-stranded RNA-dependent protein kinase
      (PKR) that has been reported to inhibit protein synthesis by phosphorylating the
      alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha).
      Autophosphorylation was characterized by a shift up in mobility of PKR on
      SDS/PAGE gels from a 60- to a 64-kDa form. In vitro kinase studies comparing the
      autophosphorylated 64-kDa PKR with the nonphosphorylated 60-kDa PKR confirmed
      that only the 64-kDa form was active for eIF-2 alpha phosphorylation. PKR
      activation in vivo was associated with phosphorylation of eIF-2 alpha and
      inhibition of protein synthesis. Addition of IL-3 to deprived cells elicited a
      reciprocal response characterized by the rapid dephosphorylation of PKR and eIF-2
      alpha, indicating inactivation of PKR. This was rapidly followed by the full
      recovery of protein synthesis. Furthermore, upon IL-3 addition, a 97-kDa
      phosphotyrosine-containing protein becomes rapidly and transiently associated
      with PKR prior to dephosphorylation of PKR and eIF-2 alpha. Genistein, a tyrosine
      kinase inhibitor, blocks both phosphorylation of the 97-kDa phosphoprotein and
      protein synthesis after IL-3 addition, suggesting a role for the 97-kDa
      phosphoprotein in the mechanism of inactivation of PKR and stimulation of protein
      synthesis. Thus, IL-3 appears to positively regulate protein synthesis by
      inducing the inactivation of PKR in a growth factor signaling pathway.

PMID- 7519780
TI  - Src kinase associates with a member of a distinct subfamily of protein-tyrosine
      phosphatases containing an ezrin-like domain.
AB  - A 6.2-kb full-length clone encoding a distinct protein-tyrosine phosphatase (PTP;
      EC 3.1.3.48), PTPD1, was isolated from a human skeletal muscle cDNA library. The
      cDNA encodes a protein of 1174 amino acids with N-terminal sequence homology to
      the ezrin-band 4.1-merlin-radixin protein family, which also includes the two
      PTPs H1 and MEG1. The PTP domain is positioned in the extreme C-terminal part of
      PTPD1, and there is an intervening sequence of about 580 residues without any
      apparent homology to known proteins separating the ezrin-like and the PTP
      domains. Thus, PTPD1 and the closely related, partially characterized, PTPD2
      belong to the same family as PTPH1 and PTPMEG1, but because of distinct features
      constitute a different PTP subfamily. Northern blot analyses indicate that PTPD1
      and PTPD2 are expressed in a variety of tissues. In transient coexpression
      experiments PTPD1 was found to be efficiently phosphorylated by and associated
      with the src kinase pp60src.

PMID- 7519781
TI  - Continuous network of endoplasmic reticulum in cerebellar Purkinje neurons.
AB  - Purkinje neurons in rat cerebellar slices injected with an oil drop saturated
      with 1,1'-dihexadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate
      [DiIC16(3) or DiI] to label the endoplasmic reticulum were observed by confocal
      microscopy. DiI spread throughout the cell body and dendrites and into the axon.
      DiI spreading is due to diffusion in a continuous bilayer and is not due to
      membrane trafficking because it also spreads in fixed neurons. DiI stained such
      features of the endoplasmic reticulum as densities at branch points, reticular
      networks in the cell body and dendrites, nuclear envelope, spines, and aggregates
      formed during anoxia nuclear envelope, spines, and aggregates formed during
      anoxia in low extracellular Ca2+. In cultured rat hippocampal neurons, where
      optical conditions provide more detail, DiI labeled a clearly delineated network
      of endoplasmic reticulum in the cell body. We conclude that there is a continuous
      compartment of endoplasmic reticulum extending from the cell body throughout the
      dendrites. This compartment may coordinate and integrate neuronal functions.

PMID- 7519782
TI  - The c-kit ligand suppresses apoptosis of human natural killer cells through the
      upregulation of bcl-2.
AB  - The bcl-2 protein plays a central role in the regulation of programmed cell death
      in a variety of tissues and is pivotal to the survival of lymphocytes in vivo.
      The growth factors responsible for survival of normal lymphocytes are unknown but
      are likely to maintain viability in part through the regulation of bcl-2
      expression. A subset of human natural killer (NK) cells (CD3-CD56bright) are
      unique among lymphocytes in their constitutive expression of c-kit, a tyrosine
      kinase cell surface receptor that binds c-kit ligand (KL). Alone, KL does not
      promote proliferation or further differentiation of CD56bright NK cells. We now
      report that, in the absence of serum or additional growth factors, KL prevents
      apoptosis of cultured CD56bright NK cells, as assessed by DNA fragmentation
      studies, and maintains viability, as measured by biologic responses (i.e.,
      proliferation and cytotoxicity) to the subsequent addition of other cytokines.
      Furthermore, we demonstrate that KL induces CD56bright NK cells to express the
      bcl-2 protein. In the presence of anti-c-kit antibody, the tyrosine kinase
      inhibitor genistein, or bcl-2 antisense oligonucleotide, the protective effect of
      KL on the survival of CD56bright NK cells is dramatically reduced. These data
      demonstrate that the binding of KL to its tyrosine kinase receptor results in the
      upregulation of bcl-2, thereby preventing apoptosis in this subset of normal
      human lymphocytes. As soluble KL is plentiful in normal human serum, this
      survival mechanism may be operative for CD56bright NK cells in vivo.

PMID- 7519783
TI  - Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin
      sensitive K channel by cGMP-dependent protein kinase.
AB  - Nitric oxide (NO)-induced relaxation is associated with increased levels of cGMP
      in vascular smooth muscle cells. However, the mechanism by which cGMP causes
      relaxation is unknown. This study tested the hypothesis that activation of Ca
      sensitive K (KCa) channels, mediated by a cGMP-dependent protein kinase, is
      responsible for the relaxation occurring in response to cGMP. In rat pulmonary
      artery rings, cGMP-dependent, but not cGMP-independent, relaxation was inhibited
      by tetraethylammonium, a classical K-channel blocker, and charybdotoxin, an
      inhibitor of KCa channels. Increasing extracellular K concentration also
      inhibited cGMP-dependent relaxation, without reducing vascular smooth muscle cGMP
      levels. In whole-cell patch-clamp experiments, NO and cGMP increased whole-cell K
      current by activating KCa channels. This effect was mimicked by intracellular
      administration of (Sp)-guanosine cyclic 3',5'-phosphorothioate, a preferential
      cGMP-dependent protein kinase activator. Okadaic acid, a phosphatase inhibitor,
      enhanced whole-cell K current, consistent with an important role for channel
      phosphorylation in the activation of NO-responsive KCa channels. Thus NO and cGMP
      relax vascular smooth muscle by a cGMP-dependent protein kinase-dependent
      activation of K channels. This suggests that the final common pathway shared by
      NO and the nitrovasodilators is cGMP-dependent K-channel activation.

PMID- 7519786
TI  - [Palliative therapy of inoperable esophageal carcinoma].
AB  - The life expectancy of patients with inoperable esophageal neoplasms is very
      limited. Therefore, palliative strategies should be immediately effective in
      relieving dysphagia. The efficiency of different methods so far available for
      palliation is discussed. In inoperable localized cancers, combined chemotherapy
      and radiation therapy are more effective than irradiation alone. Patients with
      more advanced carcinomas will benefit from the development of self-expanding
      metal stents. These stents can be placed quickly, are safe and show low morbidity
      rates.

PMID- 7519784
TI  - Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to
      endothelium in vivo.
AB  - A common feature of cigarette-smoke (CS)-associated diseases such as
      atherosclerosis and pulmonary emphysema is the activation, aggregation, and
      adhesion of leukocytes to micro- and macrovascular endothelium. A previous study,
      using a skinfold chamber model for intravital fluorescence microscopy in awake
      hamsters, has shown that exposure of hamsters to the smoke generated by one
      research cigarette elicits the adhesion of fluorescently labeled leukocytes to
      the endothelium of arterioles and small venules. By the combined use of
      intravital microscopy and scanning electron microscopy, we now demonstrate in the
      same animal model that (i) CS-induced leukocyte adhesion is not confined to the
      microcirculation, but that leukocytes also adhere singly and in clusters to the
      aortic endothelium; (ii) CS induces the formation in the bloodstream of
      aggregates between leukocytes and platelets; and (iii) CS-induced leukocyte
      adhesion to micro- and macrovascular endothelium and leukocyte-platelet aggregate
      formation are almost entirely prevented by dietary or intravenous pretreatment
      with the water-soluble antioxidant vitamin C (venules, 21.4 +/- 11.0 vs. 149.6 +/
      38.7 leukocytes per mm2, P < 0.01; arterioles, 8.5 +/- 4.2 vs. 54.3 +/- 21.6
      leukocytes per mm2, P < 0.01; aortas, 0.8 +/- 0.4 vs. 12.4 +/- 5.6 leukocytes per
      mm2, P < 0.01; means +/- SD of n = 7 animals, 15 min after CS exposure). No
      inhibitory effect was observed by pretreatment of the animals with the lipid
      soluble antioxidants vitamin E or probucol. The protective effects of vitamin C
      on CS-induced leukocyte adhesion and aggregation were seen at vitamin C plasma
      levels (55.6 +/- 22.2 microM, n = 7) that can easily be reached in humans by
      dietary means or supplementation, suggesting that vitamin C effectively
      contributes to protection from CS-associated cardiovascular and pulmonary
      diseases in humans.

PMID- 7519785
TI  - Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated
      in vitro neutralization.
AB  - Hepatitis C virus (HCV) is the most important etiologic agent of non-A, non-B
      hepatitis and is a major cause of chronic liver disease and hepatocellular
      carcinoma. Development of an effective vaccine would be the most practical method
      for prevention of the infection, but whether infection with HCV elicits
      protective immunity in the host is unclear. Neutralization of HCV in vitro was
      attempted with plasma of a chronically infected patient, and the residual
      infectivity was evaluated by inoculation of eight seronegative chimpanzees. The
      source of HCV was plasma obtained from a patient during the acute phase of
      posttransfusion non-A, non-B hepatitis, which had previously been titered for
      infectivity in chimpanzees. Neutralization was achieved with plasma obtained from
      the same patient 2 yr after the onset of primary infection but not with plasma
      obtained 11 yr later, although both plasmas contained antibodies against
      nonstructural and structural (including envelope) HCV proteins. Analysis of
      sequential viral isolates from the same patient revealed significant genetic
      divergence as early as 2 yr after infection. However, the HCV recovered from the
      patient 2 yr after the infection had a striking sequence similarity with the HCV
      recovered from one of the chimpanzees inoculated with the acute-phase virus,
      suggesting that the progenitor of the new strain was already present 2 yr
      earlier. This evidence, together with the different sequences of HCV recovered
      from the chimpanzees that received the same inoculum, confirms that HCV is
      present in vivo as a quasispecies. These results provide experimental evidence in
      vivo that HCV infection elicits a neutralizing antibody response in humans but
      suggest that such antibodies are isolate-specific. This result raises concerns
      for the development of a broadly reactive vaccine against HCV.

PMID- 7519787
TI  - Mono and polichemotherapy in the treatment of metastatic and invasive gestational
      trophoblastic disease: analysis of 50 cases.
AB  - Fifty patients with metastatic or invasive gestational trophoblastic disease
      (GTD) were admitted at the "Hospital das Clinicas" of the Ribeirao Preto School
      of Medicine of the Sao Paulo University between January 1980 and December 1990.
      Of these 50 patients, 44 (88%) had GTD following abortion, 5 (10%) after term
      pregnancies and one (2%) after an ectopic pregnancy. Thirty five (70%) had
      invasive GTD and 15 (30%) metastatic GTD. The sites of metastases were: lung, 8
      (53.3%), pelvis, 4 (26.6%), central nervous system, 2 (13.3%) and right auricle,
      1 (6.6%). Human chorionic gonadotropin, pelvic arteriography and ultrasonography
      were used in the diagnosis of invasive GTD. 25 of the 41 patients with low-risk
      metastatic and invasive GTD were treated with monochemotherapy. There were 6
      (24%) failures and the remaining 19 patients (76%) had complete remission of the
      disease after 2.89 mean cycles. Sixteen patients were treated with
      polichemotherapy, there were 2 (12.5%) failures and the remaining 14 had complete
      remission after a 2.3 mean cycles. No statistical differences between the two
      types of chemotherapy were observed. Four (8%) deaths were recorded.

PMID- 7519788
TI  - Hepatitis C virus infection in different populations in Cameroon.
AB  - We tested serum samples collected in an urban setting (Yaounde) and in a rural
      area (Manyemen) for the presence of antibody to hepatitis C virus (HCV) (anti
      HCV). Screening was done by second-generation ELISA and confirmation with second
      generation RIBA. In Yaounde, anti-HCV was found in 12.5% of patients with febrile
      jaundice (95% CL 3.8-21.2), 5.5% of pregnant women (95% CL 3.3-7.3), 0% of
      children below 4 years of age, 31% of sickle cell patients (95% CL 20.2-41.8%),
      1.6% of medical students (95% CL 0-4.7%) and 15.4% of prostitutes (95% CL 8.5
      22.3). Only HBsAg-negative sera were tested for anti-HCV, except sera originating
      from subjects with febrile jaundice. In Manyemen, anti-HCV was detected in 6.4%
      of blood donors, 6.0% of pregnant women, 5.3% of HIV-positive subjects, 7.3% of
      RPR-positive and 3.9% of RPR-negative subjects. There was an increase in antibody
      prevalence with age. We conclude that HCV infection is common in Cameroon and
      that it is transmitted mainly by blood transfusion and probably by sexual
      activity.

PMID- 7519790
TI  - [Peripheral leukocyte adhesion molecules in patients of Behcet's disease
      associated with active ocular lesions].
AB  - The sequential cascades in leukocyte adhesion and migration are important events
      in the development of inflammatory and immune responses in Behcet's disease. In
      an attempt to clarify the relation of active ocular lesions to inflammatory
      reactions covering entire body, we have detected LECAM-1, Mac-1 and CD44
      expressed on the peripheral leukocytes in 24 Behcet patients and 15 healthy
      adults by flow cytometry. LECAM-1 and CD44 expression was dramatically decreased
      from the polymorphonuclear leukocytes (PMN) upon ocular attacks, whereas the
      changes in Mac-1 appeared not so striking. This tendency had continued into the
      recovery stage of ocular inflammation. T lymphocytes showed, on the other hand,
      no considerable variability in regard to the expression of cell surface LECAM-1,
      CD44 and also of Mac-1 even at the peak of active ocular inflammation. The
      results suggest that interaction between PMN and primed vascular endothelial
      cells might be apt to precede functional modifications of T lymphocytes, and it
      is also supposed that facilitation of activated PMN recruitment plays an
      essential role on ocular inflammation in Behcet's disease.

PMID- 7519789
TI  - Voluntary screening program for prostate cancer: detection rate and cost.
AB  - In a community-wide screening program conducted in Jacksonville, Florida, 564
      participants received free screening for prostate cancer. Frequency of positive
      results of prostate-specific antigen measurement and digital rectal examination
      was comparable to that found in similar programs in other communities. The
      estimated cost for each participant was $231, and the cost to discover each
      cancer was $7,240. If one also includes initial therapy in cost estimates, then
      the cost per participant was $520, and the cost to find and treat each patient
      was $16,300. The value of screening for prostate cancer must be judged by
      treatment outcome and underlying costs.

PMID- 7519792
TI  - [The possibilities for renewed irradiation and surgical resection in previously
      treated rectal carcinoma].

PMID- 7519791
TI  - [Pathological roles of CD antigens in rheumatic diseases].

PMID- 7519793
TI  - Cellular uptake and release of the immunomodulating fungal toxin gliotoxin.
AB  - Uptake of the immunomodulating agent gliotoxin into a panel of cells using
      biosynthetically radiolabelled 35S toxin showed rapid association of the toxin
      with all cell types studied with 70-85% of the total counts in the media becoming
      cell associated. A difference in kinetics was observed for cell lines when
      compared to the primary cells thymocytes, activated T-cells and macrophages. In
      the latter uptake was maximal after 10-15 min and radiolabel was lost from the
      cells as early as 100 min. In the cell lines studied, uptake was complete in less
      than 1 min with no loss of label after 100 min. The exception to this was a Wilms
      tumour line. Analysis of the fate of gliotoxin taken up into sensitive (activated
      T-cells) and resistant (human fibroblast) cells by HPLC showed: (a) up to 30% of
      the original gliotoxin taken up by sensitive cells was released as free gliotoxin
      over a 22 hr period. The remainder was metabolized to inorganic sulphate; (b) in
      T-cells gliotoxin is reduced to the dithiol form in significant amounts and this
      reduction may be modulated by glutathione; and (c) no reduced gliotoxin could be
      detected in the resistant fibroblast cell line 27Sk even though up to 50% of the
      original gliotoxin was still present in the free form in these cells at 22 hr.
      Gliotoxin became covalently associated with macromolecules in both cell types
      studied. Very little free gliotoxin is released into extracellular medium by the
      fibroblast cell line. Gliotoxin at 500 nM was found to induce apoptosis or
      programmed cell death in the Wilms tumour cell line but not in any other cell
      line studied, and this may account for the different kinetics of release of the
      toxin from the Wilms tumour cell line.

PMID- 7519794
TI  - New polymorphism on platelet glycoprotein IIIa gene recognized by endonuclease
      Msp I: implications for PlA typing by allele-specific restriction analysis.
AB  - BACKGROUND: Five human platelet alloantigen systems have been shown to result
      from single base pair substitutions in encoding regions of platelet glycoprotein
      genes IIIa, Ib, IIb, and Ia. For each of the diallelic systems, at least one
      restriction enzyme is known to cut only one of the two haplotypes. In the PlA
      system, restriction endonucleases Nci I and Msp I both recognize the PlA2 allele.
      STUDY DESIGN AND METHODS: A causal observation of an unexpected Msp I restriction
      pattern of a PlA2/PlA2 individual was made. Samples from 261 blood donors were
      then typed for antigens of the PlA system by restriction fragment length
      polymorphism analysis using the Nci I and Msp I restriction enzymes. RESULTS:
      Applying both enzymes, concordant restriction patterns were found in 258 of 261
      blood donors. Three donors had a base pair mutation on the PlA2 allele, which
      creates an additional restriction site for Msp I 20 base pairs downstream from
      the PlA polymorphic site. Nucleotide sequence analysis revealed a CT217-->CG217G
      base exchange resulting in a Leu40-->Arg40 polymorphism of glycoprotein IIIa.
      CONCLUSION: Presuming that the mutation is not a singular phenomenon and also
      occurs with the PlA1 haplotype, it could lead to false interpretations of
      restriction analysis with Msp I. To exclude that possibility, Nci I is preferred
      for restriction fragment length polymorphism typing in the PlA system.

PMID- 7519795
TI  - Detection and characterization of hepatitis C virus RNA in immune globulins.
AB  - BACKGROUND: Hepatitis C virus (HCV) RNA was measured in immune globulins and its
      chemical and physical properties were characterized. STUDY DESIGN AND METHODS:
      The study examined 69 immune globulin lots from 7 manufacturers, including 44
      intravenous and 25 intramuscular immune globulin preparations. In addition, 8
      experimental intravenous immune globulin preparations were investigated.
      Detection and quantitation of HCV RNA were achieved by reverse transcription and
      nested polymerase chain reaction at limiting dilution. A multi-antigen anti-HCV
      enzyme immunoassay was also used to test these immune globulins. RESULTS: The
      highest level of HCV RNA was found in an experimental immune globulin lot derived
      from a plasma pool made up of 186 anti-c100-3-reactive units. HCV RNA was
      detected only in 1 of 7 manufacturers' experimental intravenous immune globulin
      preparations derived from a pool made up of 2887 anti-c100-3-negative units. It
      was also detected in commercial intravenous immune globulin lots prepared by the
      same manufacturer from source plasma, but not from recovered plasma. More than
      half of the commercial intramuscular immune globulin lots, including specific
      immune globulin products, were HCV RNA positive. All immune globulin products
      examined were reactive for anti-HCV. Certain similarities were found for HCV RNA
      present in an immune globulin product and plasma. Ethanol at 20 or 25 percent had
      no effect upon the buoyant density of HCV RNA. CONCLUSION: Many immune globulin
      preparations contained HCV RNA, with levels depending upon both the type of
      starting plasma and the manufacturing process. Exposure to ethanol did not appear
      to affect the physical characteristics of HCV RNA.

PMID- 7519796
TI  - Confirmation of hepatitis C infection: a comparison of five immunoblot assays.
AB  - BACKGROUND: Recently, new immunoblot assays for the detection of antibodies to
      hepatitis C virus (HCV) became available. STUDY DESIGN AND METHODS: The
      performance of five confirmatory anti-HCV immunoblot assays was studied with
      samples with known HCV antibody and HCV RNA status. The assays were a third
      generation strip recombinant immunoblot assay (RIBA-3, Chiron Corp., Emeryville,
      CA), a second-generation HCV blot (DB-2 blot, Diagnostic Biotechnology,
      Singapore), the Wellcozyme HCV Western blot (Murex blot, Murex Diagnostics,
      Dartford, UK), an immunodot HCV assay (Matrix, Abbott Laboratories, Chicago, IL),
      and the third-generation HCV line immunoassay (Liatek-III, Organon Teknika,
      Boxtel, The Netherlands). RESULTS: Sensitivity on samples from 48 HCV RNA
      positive, second-generation RIBA (RIBA-2)-positive persons and specificity on
      samples from 31 low-risk donors was 96 percent or better for all assays. The
      sensitivity on 31 HCV RNA-positive, RIBA-2-indeterminate samples was as follows:
      Liatek-III, 94 percent; RIBA-3, 90 percent; Murex blot, 61 percent; Matrix, 55
      percent; and DB-2 blot, 39 percent. In testing 39 HCV RNA-negative, RIBA-2
      indeterminate donor samples, the percentage found to be negative was Liatek-III,
      77 percent; RIBA-3, 67 percent; Murex blot, 49 percent; DB-2 blot, 33 percent;
      and Matrix, 15 percent. The order of sensitivity on four HCV seroconversion
      series was (from high to low): RIBA-3, Liatek-III, DB-2 blot, Murex blot, and
      Matrix; the differences were small. CONCLUSION: Detection of HCV antibodies was
      not refined by the addition of new HCV antigens (NS5, E2/NS1), but by improved
      classical antigens (core, NS3, NS4). Replacement of the commonly used RIBA-2 will
      resolve the status of a high proportion of RIBA-2-indeterminate samples.

PMID- 7519797
TI  - FPTT is a low-incidence Rh antigen associated with a "new" partial Rh D
      phenotype, DFR.
AB  - BACKGROUND: Several Rh D phenotypes with partial D antigens are recognized. Some
      partial D antigens are associated with low-incidence Rh antigens. New partial D
      antigens are revealed by an atypical pattern of reactions with anti-D. STUDY
      DESIGN AND METHODS: The reactions of D variant cells with panels of monoclonal
      anti-D and with antibodies to low-incidence antigens were compared to those of
      known D categories to identify a new Rh D phenotype. The inheritance of partial D
      antigens was studied by Rh phenotyping of the families of the probands. Standard
      serologic methods were used and family data were analyzed. RESULTS: A new Rh D
      phenotype, to be called DFR, was identified in 17 probands, two of whom had made
      anti-D. The partial D antigen carries epD3, epD4, and epD9 and lacks epD8. The
      presence of other D epitopes is ambiguous; different answers were obtained for
      the same sample with different monoclonal anti-D of the same apparent epitope
      specificity. The immunoglobulin class of the anti-D was important: IgG were more
      successful than IgM monoclonal anti-D in detecting the partial D of DFR. Family
      studies showed that DFR traveled with Ce more frequently than with cE. The low
      incidence antigen FPTT (International Society of Blood Transfusion number 700048)
      was found on all DFR samples. Family studies demonstrated that FPTT is, as
      suspected, part of the complex Rh system. CONCLUSION: The partial D of the Rh D
      phenotype, DFR, is recognized by its pattern of reactions with monoclonal anti-D
      and its association with the low-incidence antigen FPTT, FPTT has now been
      numbered Rh50.

PMID- 7519799
TI  - Diabetogenicity of FK506 versus cyclosporine in liver transplant recipients.

PMID- 7519798
TI  - Expression and complex formation of S100-like proteins MRP8 and MRP14 by
      macrophages during renal allograft rejection.
AB  - MRP8 and MRP14, two S100-like calcium-binding proteins, are expressed during
      differentiation of monocytes/macrophages. Both assemble to different
      noncovalently associated complexes that are supposed to represent the
      biologically active states. The present study was intended to investigate the
      molecular basis of macrophage heterogeneity with respect to expression and
      complex formation of MRP8 and MRP14 during acute and chronic rejection of renal
      allografts. First, specificity of antisera and mAbs to be directed against MRP8,
      MRP14, or MRP8/MRP14 heterodimers was determined by immunocytochemical and
      Western blot analyses of L132 fibroblasts (co-)transfected with MRP8 and/or MRP14
      cDNA. Then, immunohistochemical analysis of biopsy specimens obtained from kidney
      allografts after acute rejection was performed, revealing a parallel expression
      of MRP8 and MRP14 with coincident MRP8/MRP14 heterodimer formation in
      infiltrating monocytes. In contrast, chronic allograft rejection was
      characterized by a subpopulation of monocytes defined by the absence of
      MRP8/MRP14 complex formation despite expression of MRP8 and MRP14 monomers.
      Double-labeling experiments showed that this was due in part to differential
      expression of MRP8 and MRP14 in infiltrate macrophages of chronic rejection. The
      data presented demonstrate for the first time differences in MRP8/MRP14 complex
      assembly by infiltrating monocytes in situ. These seem to be of
      pathophysiological relevance since complex formation defines subpopulations of
      monocytes associated with distinct pathways of immunological reactions.
      Differences in the mode of calcium-dependent signaling may, therefore, be of
      importance for understanding the molecular basis of macrophage heterogeneity
      during acute and chronic allograft rejection.

PMID- 7519800
TI  - Reversal of severe FK506 side effects by conversion to cyclosporine-based
      immunosuppression.

PMID- 7519801
TI  - Plasma FK506 levels in patients with histopathologically documented renal
      allograft rejection.

PMID- 7519802
TI  - Radiation therapy in epidemic, AIDS-related Kaposi's sarcoma in southern Africa.
AB  - AIMS AND BACKGROUND: Acquired Immunodeficiency Syndrome (AIDS) associated
      Kaposi's Sarcoma (EKS) is widely spread in the Southern African Region. No large
      studies concerning the role of radiation therapy in the Southern African variant
      of EKS have been reported to date. METHODS: Over a 10 year period (1982-1992) 25
      patients with EKS (disseminated skin involvement) were treated primarily with
      radiation therapy at the Johannesburg General Hospital. Radiation fields were
      individually tailored to the extent of the disease. Total administered doses
      ranged between 8-12 Gy (single fraction) to 24-30 Gy fractionated over 2-3 weeks.
      RESULTS: Overall response and symptomatic relief rates were 72% and 80%,
      respectively. Toxicity was mild and manageable. CONCLUSIONS: Our retrospective
      analysis supports the use of radiation therapy for the Southern African type of
      EKS.

PMID- 7519803
TI  - [Infections of the ejaculate by sexually transmissible pathogens].
AB  - Certain ejaculate infections can be traced back to sexually transmitted
      microorganisms, such as Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma
      urealyticum and Trichomonas vaginalis. To varying extents, these microorganisms
      cause such classical genital infections as urethritis, epididymitis and
      prostatitis as well as subclinical genital tract infections. Several different
      pathomechanisms are under discussion for infection of the ejaculate: reduction of
      spermatogenesis resulting from testicular damage, autoimmune processes induced by
      inflammation, direct influence on the spermatozoal function, disturbances in
      spermatozoal transport, secretory dysfunction of the male accessory sex glands
      and leukocytospermia with secondary influence on ejaculate parameters. The
      relevance of these microorganisms for the localization of the inflammatory
      process within the genital tract are discussed in detail. Their importance for
      male fertility is a matter of debate. In particular, the significance of C.
      trachomatis and U. urealyticum, both of which are detectable in the urethra, is
      still uncertain and cannot be assessed conclusively. Further information allowing
      delimitation of an infection resulting from bacterial colonization may be
      provided, on the one hand, by biochemical markers for an inflammatory reaction
      and indicators of an immune response in the ejaculate, e.g. PMN elastase,
      complement C3, or coeruloplasmin, and on the other hand, by secretion markers
      such as alpha-glucosidase, PSA and phosphatase. Whether the assessment of these
      markers and indicators can help to clarify the inflammatory origin of infertility
      in individual cases remains doubtful.

PMID- 7519804
TI  - [PSA in prostatic fluid].
AB  - Correct forecasting of prostatic carcinoma by means of serum PSA is limited.
      Prostatic carcinoma is said to increase PSA 10 times as much as prostatic
      adenoma. Therefore we evaluated whether PSA in the prostatic fluid is more
      specific for prostatic carcinoma than the level in the serum. In 31 consecutive
      patients with prostatic disease blood was taken for serum PSA first and then
      prostatic fluid (10 microliters) was expressed. The PSA was determined by the
      Pros-Check test in both the serum and in the prostatic fluid. The collection of
      the prostatic fluid failed in 7 (22.6%) patients. Of the remaining 24 patients, 5
      had documented bacterial prostatitis, 4 had prostatic carcinoma and 15 had benign
      prostatic hyperplasia (BPH). The serum PSA was 5.6 +/- 5.0 micrograms/l in
      prostatitis, 148 +/- 208 micrograms/l in prostatic carcinoma and 6.9 +/- 6.8
      micrograms/l in BPH. The serum PSA was significantly higher in prostatic cancer
      (P < or = 0.01) than in prostatitis and BPH. The PSA levels in the prostatic
      fluid were 14.0 +/- 25.7 x 10(6) micrograms/l in prostatitis, 7.6 +/- 9.7 x 10(6)
      micrograms/l in carcinoma and 14.0 +/- 14.6 x 10(6) micrograms/l in BPH. There
      were no statistically significant differences. In the expressed prostatic fluid
      no significantly different PSA was found in carcinoma, bacterial prostatitis or
      BPH. In contrast to this, the serum PSA was significantly higher in cancer
      patients than in prostatitis or BPH. Therefore PSA in the expressed prostatic
      fluid is no more specific than that in the serum.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7519805
TI  - Considerations in the treatment of feline hyperthyroidism.
AB  - Feline hyperthyroidism can be treated with long-term antithyroid drug
      administration, surgical thyroidectomy, or radioactive iodine. This article
      discusses the advantages of each of these treatment options and gives specific
      recommendations on the use of each therapeutic modality.

PMID- 7519806
TI  - Antigenic structure of the coat protein of potato mop-top furovirus.
AB  - The antigenic structure of the coat protein (CP) of potato mop-top furovirus
      (PMTV) was studied by electron microscopy of virus particles labeled with gold
      conjugated monoclonal antibodies (MAbs) and by the reactions of MAbs with
      overlapping octapeptides (Pepscan) representing the complete amino acid sequence
      of the CP. A total of seven epitopes were identified in the CP. MAb SCR 69
      detected a continuous epitope, which was located at the extreme N-terminus of the
      CP, was exposed at the surface along the sides of PMTV particles, and was removed
      by treating them with trypsin. MAb SCR 68 detected a discontinuous epitope found
      at the concave end of PMTV particles. Five other epitopes, which were detected by
      Pepscan tests, were located internally in, and at intervals along, the CP amino
      acid sequence. A tentative model of the PMTV CP subunit was produced, based on
      computer-aided prediction of its secondary structure and apparent similarities
      with the CP of tobacco mosaic virus. In this model, four of the epitopes occur at
      high radius in each of the pairs of parallel and anti-parallel alpha-helices in
      the CP subunit. The fifth is at low radius in the putative left radial alpha
      helix. The epitope detected by MAb SCR 77, although amenable to study by Pepscan,
      contains three reactive elements, separated by short runs of nonessential
      residues, in a sequence of 13 amino acids. In intact virus particles, the CPs of
      beet necrotic yellow vein furovirus and PMTV apparently differ in the
      accessibility of their N- and C-termini.

PMID- 7519807
TI  - Entry of coxsackievirus A9 into host cells: specific interactions with alpha v
      beta 3 integrin, the vitronectin receptor.
AB  - Attachment and entry of coxsackievirus A9 (CAV-9) to GMK cells were previously
      shown to be dependent on an arginine-glycine-aspartic acid (RGD) motif in the
      capsid protein VP1, suggesting integrins as candidate receptors for the virus. We
      have pursued the matter further and show that antibodies specific for the alpha v
      and/or beta 3 integrin subunits protect GMK cells from CAV-9 infection. Affinity
      purification of radioiodinated cell surface proteins using CAV-9 or virus
      specific peptide (RRRGDL) columns confirmed that the alpha v beta 3 heterodimer,
      known as the vitronectin receptor, is recognized by the virus in GMK cells. Other
      proteins, of lower molecular weight (less than 40 kDa), were also bound to and
      specifically eluted from the columns, but their possible role in attachment and
      entry of CAV-9 remains to be elucidated by further studies. Of several other
      related viruses studied, only echovirus 22, which also has an RGD motif in the
      VP1 capsid protein, was found to compete for cell surface binding with CAV-9.

PMID- 7519808
TI  - 1492--the medical consequences.
AB  - This discussion was selected from the weekly staff conferences in the Department
      of Medicine, University of California, San Francisco. Taken from a transcription,
      it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine,
      under the direction of Lloyd H. Smith Jr, MD, Professor of Medicine and Associate
      Dean in the School of Medicine.

PMID- 7519810
TI  - [Newly approved specialty drugs in Austria and new knowledge about already
      available specialty drugs. Proscar film tablets (Finasterid, MSD)].

PMID- 7519809
TI  - What Columbus's voyages wrought.

PMID- 7519811
TI  - Polymerase chain reaction (PCR) as a diagnostic tool in HIV infection.
AB  - We set up a PCR laboratory for the diagnosis of HIV-1. Probably due to the
      variability of the HIV-genome, classical primers that performed well in some
      laboratories in the past, did not suffice for detection of HIV-1 strains in
      Belgian hospitals. Two new primer sets amplifying a fragment in the LTR-gag gene
      and in the env gene, which perform better on strains seen in Belgium, have been
      developed and evaluated. One primer set, conceived and evaluated on Belgian
      strains by the "Instituut voor Tropische Geneeskunde" in Antwerp, was also
      included. These three primer sets performed superior (92% sensitivity and 100%
      specificity on 24 samples) than the classical primers (83.5% sensitivity and 56%
      specificity on 21 samples). Together with a well-studied testing algorithm, they
      allow the reliable identification of the presence of the HIV-1 genome. To detect
      resistance of HIV-1 to reverse transcriptase (RT) inhibitors, we developed a set
      of two overlapping nested PCR primer sets and additional sequencing primers to
      amplify and sequence the total RNA or DNA RT gene using a direct cycle sequencing
      approach of the amplified fragment. Some clinical isolates were amplified and
      sequenced. In HIV-1 isolates from TIBO R82913-treated patients we identified two
      amino acid mutations (V108I and Y188L) involved in resistance (more than 100-fold
      reduced sensitivity). In an untreated patient we identified an amino acid variant
      (I/V 179D) involved in a 7-fold reduced sensitivity to TIBO. Several other amino
      acid variants, not involved in resistance, were detected in treated and untreated
      patients. Using this sequencing technique on cultured virus isolates we also
      observed in one TIBO-treated patient a differential selection among the strains
      of the original HIV-1 pool. From this patient we isolated and sequenced a
      completely TIBO sensitive HIV-1 strain after extensive cultivation in cord blood
      lymphocytes of the original TIBO resistant HIV-1 virus pool. We could however
      identify the resistant genotype after cultivation of this resistant HIV-1 virus
      pool on CEM cells. Our study revealed that sequencing investigations on emerging
      resistance should preferentially be done with uncultured patient samples since
      viral sequences and virus-drug sensitivities obtained from isolates cultured in
      vitro may not necessarily correspond to the sequences and sensitivities of the
      dominant strain in vivo.

PMID- 7519812
TI  - [Sudeck's disease in osteoblastoma of the right talus and depression in a 12-year
      old boy. Case report].
AB  - This is a case report of a 12-year-old boy with reflex sympathetic dystrophy who
      had surgery for two benign tumors of the right talus. The reflex sympathetic
      dystrophy began before the first tumor was diagnosed and at a time when the boy
      was under emotional stress because of conflicts relating to his parents' divorce.
      The case is typical of reflex sympathetic dystrophy in children, which is only
      rarely reported. Associated with the syndrome are anxiety, depressive symptoms,
      emotional instability and acute stressful life events, which makes an
      interdisciplinary approach imperative.

PMID- 7519813
TI  - Fibrinolytic activity in experimental intracerebral hematoma.
AB  - We investigated the tissue fibrinolytic activity in an experimental model of
      intracerebral hematoma was developed in the guinea pig. Intracerebral hematoma
      was created by stereotaxically injecting 0.2 ml autologous blood into the left
      frontal lobe of a total 63 anesthetized adult male albino guinea pigs (weighing
      280-350 gr.). The fibrinolytic activity was studied using conventional
      histochemical stain techniques. 20 guinea pigs were used for developing the
      intracerebral hematoma model; in the 43 guinea pigs, the intracerebral hematomas
      were studied sequentially. Intracerebral hematoma formation failed in 10 of 43
      guinea pigs. Three guinea pigs died in the immediate postoperative period. It was
      diagnosed histopathologically purulent meningitis and ventriculitis in four
      guinea pigs. Tissue fibrinolytic activity was increased in the meninges and
      choroid plexus. No fibrinolytic activity was observed a during the first days (1
      to 3 days after hematoma production). 3 to 5 days later, fibrinolytic activity
      was seen in the capillary buds surrounding the hematoma and among the
      infiltrating mononuclear cells. This activity reached highest levels for 7-14
      days following production of the hematoma and decreased after 20 days. In
      conclusion, tissue fibrinolytic activity associated with neovascularisation and
      mononuclear cell infiltration appears to be important in lysis of intracerebral
      hematoma.

PMID- 7519814
TI  - The endoscopic management of esophageal cancer.
AB  - Cancer of the esophagus is a tumor that, at diagnosis, is often advanced and not
      curable. The traditional treatment for cancer of the esophagus is still surgery.
      Assessment of palliative treatments including radiation, YAG laser, photodynamic
      therapy, prosthesis is done.

PMID- 7519815
TI  - [Nasal hyperreactivity and neuropeptides].
AB  - The Authors define nasal-sinusal hyperreactivity and closely investigate the
      influence it has on the relationship existing among the Central Nervous System,
      Peripheric Nervous System, Immunitary System and Nasal Mucosa. Particular
      reference is made to neuropeptides that seem to be true "bridge" substances
      between the Nervous System and some components of the Immunitary System.
      Importance of the P-Substance is emphasized.

PMID- 7519816
TI  - [Nasal polyps and substance P: a preliminary report].
AB  - Nasal-sinusal polyposis is a disease with a multifactorial pathogenesis that is
      often indicative of focal hyperactivity. In the human nasal mucosa are present
      trigeminal nervous fibres which release Substance P and other neuropeptides in
      reply to multiple stimuli. Employing immunohistochemical methods the Authors
      studied the presence and the distribution of SP in tissue biopsies made during
      surgery in 18 patients with a non-allergic nasal polyposis. In 8 cases, including
      all those subjects with recurrences, an immunohistochemical positivity towards SP
      was noticed. The Authors suggest possible involvement of SP in the pathogenesis
      of some forms of nasal polyposis.

PMID- 7519817
TI  - [Serotonergic function and aggressive-impulsive behavior].
AB  - Considerable interest has been paid to the biological basis of the aggressive
      behavior, in the last two decades. The 5-HT function has been the most studied
      function in animal models, and studies carried out with either psychiatric
      patients, antisocial subjects, or normal people. An overwhelming evidence favors
      the importance of the 5-HT function in the modulation of aggressive behavior,
      particularly when 5-HT function is associated to loss of impulse control. Data
      from literature are reviewed. Results of a challenge serotonin test with
      fluoxetine in normal subjects are presented. The therapeutic implications of such
      studies are also discussed.

PMID- 7519818
TI  - Antibody response to hepatitis C virus infection after liver transplantation.
AB  - OBJECTIVE: To determine whether liver transplantation and the subsequent
      immunosuppression affect the antibody response to hepatitis C virus (HCV)
      infection. METHODS: Sera from 46 patients were compared before and after liver
      transplantation for markers of HCV infection. Serum HCV RNA was determined by
      polymerase chain reaction (PCR). Anti-HCV antibody was determined by first- and
      second-generation immunoassays as well as a quantitative assay of the titer of
      anti-HCV core antibody. RESULTS: Among individuals who acquired hepatitis C
      infection in association with liver transplantation, only 15% (3/12) developed
      antibody to the core antigen and only 25% (3/12) reacted to any antigen present
      on the second-generation recombinant immunoblot assay after a mean follow-up
      period of 18 months. Thirty-eight percent (5/13) were positive, by the second
      generation enzyme immunoassay (EIA-2) Whereas 94% (16/17) of the individuals who
      had detectable anti-HCV core antibodies pretransplant continued to have such
      antibodies after transplant, the titer of these antibodies declined an average of
      4-fold. No significant change was seen in the antibody titer toward rotavirus, a
      common viral pathogen. Patients who acquired HCV infection or in whom the
      allograft became reinfected had a significantly increased incidence of
      posttransplant hepatitis (61% vs. 33%, respectively). CONCLUSIONS: Liver
      transplantation and posttransplant immunosuppression lead to an attenuated
      antibody response to hepatitis C viral infection. Currently available assays for
      anti-HCV antibodies may be unreliable in the posttransplant setting.

PMID- 7519819
TI  - Chronic hepatitis C and markedly elevated serum alpha-fetoprotein: complete
      response to treatment with alpha-interferon.

PMID- 7519820
TI  - Better palliation of pancreatic cancer: one stent or two?

PMID- 7519821
TI  - Choroidal neovascularization in a patient with adult foveomacular dystrophy and a
      mutation in the retinal degeneration slow gene (Pro 210 Arg)

PMID- 7519822
TI  - Increased expression of intercellular adhesion molecules in biliary atresia.
AB  - The expression of the inflammatory adhesion molecules intercellular adhesion
      molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion
      molecule-1, was studied in six infants with biliary atresia using an
      immunoperoxidase technique on frozen sections. Controls consisted of five
      patients with various conditions including total parenteral nutrition-induced
      cholestasis, choledochal cyst, viral hepatitis, metastatic carcinoma, and
      thrombotic thrombocytopenic purpura. None of the patients were in liver failure.
      Bile ducts from the control subjects did not express any of the inflammatory
      adhesion molecules on ductal epithelium. In marked contrast, all of the biliary
      atresia specimens demonstrated strong intercellular adhesion molecule-1
      expression and occasional vascular cell adhesion molecule-1 staining on
      epithelial cell membranes of both intra- and extrahepatic ductal structures.
      Hepatocytes and sinusoidal lining cells including Kupffer cells showed a pattern
      of intense intercellular adhesion molecule-1 and vascular cell adhesion molecule
      1 expression in all specimens with active inflammation that could not
      differentiate the biliary atresia cases from the control group. Lymphocyte
      function-associated antigen-1 intensely stained the inflammatory cell infiltrate
      in the biliary atresia and inflamed control specimens. The strong expression of
      intercellular adhesion molecule-1 on biliary ductal epithelium in patients with
      biliary atresia suggests a potential role for this adhesion molecule in the
      pathogenesis of this devastating neonatal hepatic disorder.

PMID- 7519823
TI  - CD5 expression in thymic carcinoma.
AB  - To determine the differences between the cellular characteristics of thymic
      carcinoma and thymoma, immunohistochemical analysis with lymphocyte markers
      (CD1a, 3, 4, 5, 8, 10, 20, 21, 25, 30, 57, and 72) was performed on 23 thymic
      epithelial tumors other than lymphocytic thymoma: overt thymic carcinoma (OC, n =
      7), atypical thymoma (n = 5), and typical thymoma (epithelial or mixed thymoma, n
      = 11). Among the surface antigens examined, CD5, a type of receptor molecule that
      signals cell growth in T cells, was expressed in neoplastic epithelial cells of
      the thymus, in OC (seven of seven) and atypical thymoma (two of five), but not in
      typical thymoma. Double labeling immunofluorescence demonstrated expression of
      CD5 in cytokeratin-positive cells. The CD5 molecule extracted from an OC tumor
      showed the same molecular size as that in the spleen, but CD72, a ligand of CD5
      on the surface of B cells, was not found in the epithelial cells of OC or
      atypical thymoma. Expression of CD5 was not observed in carcinomas of other
      organs, such as lung (n = 15), breast (n = 4), esophagus (n = 6), stomach (n =
      6), colon (n = 9), and uterine cervix (n = 3). CD5 is closely related to
      morphological changes in thymic epithelial tumors and may play a role in the
      evolution of OC through receptor-ligand interaction.

PMID- 7519824
TI  - Cathepsin B expression in colorectal carcinomas correlates with tumor progression
      and shortened patient survival.
AB  - Cathepsin B is a lysosomal cysteine proteinase that has the ability to degrade
      several extracellular matrix components at both neutral and acidic pH and has
      been implicated in the progression of several human and rodent tumors. We have
      studied the expression of cathepsin B in human colorectal tissues using a
      monospecific polyclonal rabbit antibody raised against human liver cathepsin B.
      In immunoblots of normal and neoplastic colorectal tissues this antibody
      specifically recognized only cathepsin B. We studied 101 cases of formalin-fixed,
      paraffin-embedded tissue (15 normal mucosa, 17 adenomas, and 69 carcinomas).
      Epithelial cells of normal mucosa and adenomas were either negative or showed a
      weak granular reactivity located in the paranuclear and apical cytoplasm of
      superficial cells. Small clusters of histiocytes were also positive in the region
      of the superficial area of the lamina propria. In carcinomas, increased
      expression of cathepsin B correlated with advanced stage of the disease.
      Increased immunoreactivity of cathepsin B in malignant cells was associated with
      either a diffuse cytoplasmic staining or was polarized to the basal pole of the
      cells. This is in contrast to the punctate paranuclear staining pattern observed
      in normal colonic mucosal cells. In tumor stromal cells, increased expression of
      the enzyme correlated with neoplastic progression. Expression of high levels of
      cathepsin B in the tumor epithelial cells was associated with a significantly
      shorter survival of the patients. In conclusion, our results indicate that
      cathepsin B expression is up-regulated in human colorectal carcinomas compared
      with normal mucosa and adenomas and correlates with tumor progression.

PMID- 7519825
TI  - Cytokine production and expression of adhesion molecules and integrins in tumor
      infiltrating lymphomononuclear cells of non-small cell carcinomas of the lung.
AB  - Localization of intercellular adhesion molecule-1 and vascular cell adhesion
      molecule-1, and of their ligands, lymphocyte function-associated antigen-1 and
      very late activation antigen-4, was determined in non-small cell lung carcinomas
      and tumor-free lung. Messenger RNA expression for interleukins (IL) IL-1 beta, IL
      2, IL-4, IL-5, IL-6, IL-10, tumor necrosis factor-alpha, transforming growth
      factor-beta, interferon-gamma, granulocyte-macrophages colony stimulating factor,
      and human perforin-1 was assessed by in situ hybridization on the same tissues.
      Intercellular adhesion molecule-1 was expressed in all blood vessels, whereas
      only a low number of vessels displayed vascular cell adhesion molecule-1
      immunoreactivity. Tumor infiltrating lymphomononuclear cells consisted of
      lymphocyte function-associated antigen-1-positive cells and of a lower number of
      very late activation antigen-4-positive cells. All squamous cell carcinomas
      consisted of intercellular adhesion molecule-1-positive neoplastic cells
      infiltrated by lymphocyte function-associated antigen-1-positive tumor
      infiltrating lymphomononuclear and CD-la-positive Langerhans cells, whereas only
      a minor number of adenocarcinomas displayed a consistent number of intercellular
      adhesion molecule-1-positive neoplastic cells. Tumor infiltrating
      lymphomononuclear cells showed a wider production of cytokines when compared to
      bronchus-associated lymphoid tissue of tumor-free lung. Moreover, cells producing
      interferon-gamma, IL-4, and IL-5 were more numerous in squamous cell carcinomas
      than in adenocarcinomas. These findings indicate that the lung squamous cell
      carcinoma might represent a neoplastic microenvironment able to induce activation
      of tumor infiltrating lymphomononuclear cells more efficiently than the
      adenocarcinoma.

PMID- 7519826
TI  - Expression of Bcl-2 protein and Fas antigen in non-Hodgkin's lymphomas.
AB  - Expression of Bcl-2 protein and Fas antigens was analyzed in 12 cases of
      follicular lymphoma and 32 cases of diffuse lymphoma, including 22 B-cell and 10
      T-cell lymphomas. It was shown that 75% of follicular lymphomas had clear
      expression of both Bcl-2 protein and Fas antigen. Thus, follicular lymphomas may
      have a growth advantage due to their high expression of Bcl-2 protein, which
      tended to impede apoptosis mediated by Fas antigen. On the other hand, diffuse
      lymphomas showed various patterns; 28% were double positive, 16% were only Bcl-2
      protein-positive, 28% were only Fas antigen-positive, and 28% were double
      negative or equivocal. Cytocidal assay of seven leukemia/lymphoma cell lines
      using anti-human Fas monoclonal antibody revealed that overexpression of Bcl-2
      protein tended to impede apoptosis mediated by Fas antigen. However, this
      inhibitory effect of Bcl-2 protein was incomplete and its effect might be
      dependent upon cell type.

PMID- 7519827
TI  - Specific loss of chromosomes 1, 2, 6, 10, 13, 17, and 21 in chromophobe renal
      cell carcinomas revealed by comparative genomic hybridization.
AB  - We analyzed 19 chromophobe renal cell carcinomas by means of comparative genomic
      hybridization. Two tumors revealed no numerical abnormalities. In the remaining
      17 cases we found loss of entire chromosomes with underrepresentation of
      chromosome 1 occurring in all 17 cases; loss of chromosomes 2, 10, and 13 in 16
      cases; loss of chromosomes 6 and 21 in 15 tumors; and loss of chromosome 17 in 13
      cases. The loss of the Y chromosome was observed in 6 of 13 tumors from male
      patients, whereas 1 X chromosome was lost in 3 of 4 tumors obtained from females.
      Comparative genomic hybridization results were verified by interphase
      cytogenetics. We conclude that a specific combination of multiple chromosomal
      losses characterizes chromophobe renal cell carcinomas and may help to
      differentiate them unequivocally from other types of kidney cancer.

PMID- 7519828
TI  - Monoclonal antibody blockade of L-selectin inhibits mononuclear leukocyte
      recruitment to inflammatory sites in vivo.
AB  - L-selectin interacting with inducible endothelial counterreceptors mediates in
      part the initial adhesive interactions, termed rolling, between circulating blood
      leukocytes and vascular endothelium. While blockade of L-selectin function in in
      vivo models of inflammation reduces both neutrophil and lymphocyte influx at
      early times, little is known concerning the role of L-selectin in leukocyte
      recruitment at later times (> 24 hours). Using an in vivo murine model of
      experimentally induced inflammation of the peritoneum, the role of L-selectin in
      recruitment of mononuclear leukocytes to chronic sites of inflammation (48 hours)
      was investigated. Saturating levels of function blocking anti-L-selectin
      monoclonal antibody (MEL-14) or control rat IgG were maintained for 48 hours
      using surgically implanted mini-osmotic pumps; this treatment did not alter the
      circulating leukocyte cell count or differential. In animals receiving MEL-14
      monoclonal antibody (MAb), macrophage and lymphocyte accumulation in response to
      thioglycollate was reduced by 60% (P < or = 0.0002) and > 90% (P < 0.001),
      respectively, at 48 hours as compared with animals implanted with pumps
      containing saline. Similarly, MEL-14 MAb dramatically inhibited granulocyte
      influx by 80% (P < 0.03) at 6 hours; recruitment at 24 and 48 hours was reduced
      by 50%. In contrast, the effects of purified rat IgG was not significantly
      different from saline. Our results suggest L-selectin, interacting with its
      inducible endothelial counterreceptor(s), plays an important role in circulating
      mononuclear leukocyte extravasation at sites of inflammation.

PMID- 7519829
TI  - Cytochemical staining for beta 1,6 branching of asparagine-linked
      oligosaccharides in variants of metastatic human colon carcinoma cells.
AB  - A positive correlation between tumor progression in human colon and increased
      beta 1,6 branching in oligosaccharides has recently been demonstrated. The
      present study was undertaken to elucidate whether such a correlation can be
      extended to variants of metastasizing human colon carcinoma HCT116 cells. The
      Phaseolus vulgaris leukoagglutinating lectin, which binds to beta 1,6 branched
      oligosaccharides, was employed. In blots, a band of approximately 140 kd was
      detectable in both the HCT116a and HCT116b sublines. However, in the more
      aggressive subline HCT116a, the intensity of this band was increased by 100%, and
      additional reactive bands of approximately 100 kd and approximately 170 kd were
      observed. Analysis by electron microscopy revealed lectin labeling in the Golgi
      apparatus, lysosomal elements, mucus droplets, cytoplasmic vesicles, and at the
      plasma membrane. Quantification of the lectin plasma membrane labeling revealed a
      significantly higher labeling intensity in HCT116a cells than in HCT116b cells.
      The difference in lectin plasma membrane labeling intensity could also be
      observed in paraffin sections. Thus, variants of metastatic HCT116 colon
      carcinoma cells differ quantitatively and qualitatively in glycoproteins carrying
      beta 1,6 branches.

PMID- 7519831
TI  - Retinal and choroidal neovascularization in a transgenic mouse model of sickle
      cell disease.
AB  - A complication of sickle cell disease is proliferative retinopathy. We
      investigated the eyes from a transgenic mouse model of sickle cell disease (alpha
      H beta S[beta MDD] type) to determine if pathological changes occurred in their
      retinas and choroids. One retina from each animal was processed by flat-embedding
      adenosine diphosphatase-reacted retinas in glycol methacrylate. The fellow eye
      from each animal was embedded whole in glycol methacrylate for histopathological
      analysis of all ocular structures. Retinal vascular occlusions resulted in
      nonperfused areas of retina and arterio-venous anastomoses. Intra- and
      extraretinal neovascularization was observed adjacent to nonperfused areas.
      Retinal pigmented lesions were formed by the migration of retinal pigment
      epithelial cells into sensory retina, often ensheathing choroidal
      neovascularization. The incidence of this bilateral chorioretinopathy was 30% in
      animals older than 15 months of age. The ocular histopathological changes we
      observed in the mouse model mimicked many aspects of human proliferative sickle
      cell retinopathy. Furthermore, this is the first genetically derived animal model
      for chorio-retinal neovascularization.

PMID- 7519830
TI  - Proliferative activity is a significant prognostic factor in male breast
      carcinoma.
AB  - The proliferative activity of male breast carcinoma has been investigated using
      the staining of the argyrophilic nucleolar organizer regions (AgNORs), the
      monoclonal antibody against the proliferating cell nuclear antigen (PC10) and the
      monoclonal antibody MIB-1 in formalin-fixed, paraffin-embedded specimens from 27
      primary male breast carcinomas at diagnosis. A significant correlation was found
      between survival and AgNOR counts (median of survival 77 months for cases with
      AgNOR/cell < or = 7.27 but 37 months only for cases with > 7.27 AgNOR/cell; P =
      0.001), proliferating cell nuclear antigen scores (median of survival 73 months
      for cases with proliferating cell nuclear antigen < or = 18.25% versus 41 for
      cases with proliferating cell nuclear antigen > 18.25%; P = 0.013) and MIB-1
      scores (median of survival 73 months for cases with MIB-1 scores < or = 23.5%
      versus 37 months for cases with MIB-1 scores > 23.5%; P = 0.01). Tumor
      histological grade was also correlated with prognosis (median of survival 72
      months for grade 2 versus 33 months for grade 3 tumors; P = 0.01). Estrogen and
      progesterone receptors, immunohistochemically detected on paraffin-embedded
      sections, had no prognostic value. In the multivariate survival analysis, only
      AgNOR counts (P = 0.007) and tumor size (P = 0.003) had an independent prognostic
      significance. Our results indicate that methods for assessing the cell
      proliferation in routinely processed specimens offer significant prognostic
      information in male breast carcinoma. The finding, together with the lack of
      prognostic significance for estrogen receptors and progesterone receptors,
      suggests that male breast carcinoma is biologically different from female breast
      cancer.

PMID- 7519832
TI  - The effect of an intraluminal stent on neointimal hyperplasia at an end-to-side
      polytetrafluoroethylene graft arterial anastomosis.
AB  - BACKGROUND: Anastomotic neointimal hyperplasia plays a significant role in the
      late failure of infrainguinal prosthetic arterial bypass grafts. Previous work
      from our laboratory revealed that placing a stent across an end-to-end arterio
      arterial anastomosis resulted in an increase in the luminal area as well as in
      the intimal thickness (IT) at the anastomotic level. This study was designed to
      evaluate the effects on neointimal hyperplasia when a stent is placed across an
      end-to-side polytetrafluoroethylene (PTFE) graft arterial anastomosis. METHODS: A
      canine model of an end-to-side anastomosis was developed using a 12 x 6 mm
      polytetrafluoroethylene aortobi-iliac graft. A self-expanding stainless steel
      Wallstent was placed across one randomly selected distal anastomosis leaving the
      opposite side as a control. Dogs were sacrificed at 4 and 12 weeks. At sacrifice,
      the graft and intact anastomoses were pressure-perfusion fixed with
      glutaraldehyde. Sections of each distal graft, anastomosis, and recipient artery
      were obtained for analysis. Computer images of each section were digitized to
      determine the luminal area and the mean IT. The data were analyzed statistically
      using univariate repeated measures of analysis of variance. RESULTS: One animal
      died prior to early sacrifice. Eight of 10 graft limbs remained patent at
      sacrifice. Of the 2 limbs that occluded, one was stented and one was nonstented.
      At 4 weeks, stented graft limbs had significantly greater IT at the proximal
      stent level (mean difference between control and stented sides 0.163 mm +/-
      0.054, P = 0.01). Stented and nonstented anastomoses had similar luminal area and
      IT at other levels where sections were taken. At 12 weeks, control limbs had
      significantly greater IT at the anastomotic level compared to the 4-week
      measurements (mean difference 12 weeks versus 4 weeks 0.185 mm +/- 0.06, P =
      0.006). In the stented limbs, IT at the anastomotic level had stabilized and was
      not significantly thicker than at 4 weeks. The control limbs had greater IT at
      the anastomotic level than the stented limbs (mean difference between controls
      and stented sides at 12 weeks 0.091 mm +/- 0.044, P = 0.06). At the proximal end
      of the stent, IT progressed significantly between the 4th and 12th weeks (mean
      difference 12 weeks versus 4 weeks 0.155 mm +/- 0.06, P = 0.02). The IT at the
      proximal end of the stent at 12 weeks was significantly greater than the IT at a
      comparable level in the controls (mean difference stent versus control 0.132 mm
      +/- 0.05, P = 0.04). The luminal area in the control limbs was significantly
      greater than in the stented anastomoses at levels corresponding to either end of
      the stent (mean difference at proximal end 4.163 mm2 +/- 1.633, P = 0.01; mean
      difference at distal end 7.192 mm2 +/- 1.633, P = 0.0005). However, there was no
      difference in luminal area at the anastomotic level. CONCLUSION: We conclude that
      the presence of an intraluminal stent alters the siting and degree of anastomotic
      neointimal hyperplasia in a canine model of an end-to-side anastomosis resulting
      in translocation of the intimal hyperplastic response to the proximal graft stent
      interface in a magnitude similar to that which would normally be found at the
      anastomosis.

PMID- 7519833
TI  - Subfractional analysis of cyanobacterial membranes and isolation of plasma
      membranes by aqueous polymer two-phase partitioning.
AB  - The present work demonstrates that partition in aqueous polymer two-phase systems
      offers a rapid method for separation and isolation of thylakoid, plasma, and
      outer membranes from cyanobacteria. Pure plasma membranes from Phormidium
      laminosum can be isolated by this method within 3 h, starting with total
      membranes obtained by French press treatment of the cyanobacterial cells. The
      isolated plasma membranes have a broad density profile, giving rise to three
      subpopulations. The main fraction has the same density as the abundant thylakoid
      membranes. This fraction has not been resolved in previous separations based on
      sucrose gradient centrifugation, which is the only method previously used for
      isolation of cyanobacterial plasma membranes. Another advantage of the aqueous
      polymer two-phase system is that it can handle large quantities of starting
      material, which is essential to obtain a satisfactory yield since plasma
      membranes constitute only a very small fraction of the total membrane content in
      a cyanobacterial cell. The isolation procedure results in a pure plasma membrane
      preparation with retained cytochrome c oxidase activity. The results also point
      to the possibility of a lateral heterogeneity in the organization of the
      cyanobacterial plasma membrane.

PMID- 7519834
TI  - A ruthenium-103 red dot blot assay specific for nanogram quantities of sulfated
      glycosaminoglycans.
AB  - Ruthenium-103 red has been used previously to detect nanogram quantities of
      glycosaminoglycans after they have been separated by electrophoresis on cellulose
      diacetate. We have applied the critical electrolyte principle to the binding of
      this dye to polyanions. This eliminates interaction with nucleic acids and
      hyaluronan. After samples are digested with chondroitinase ABC the method allows
      the measurement of chondroitin sulfates and heparan sulfates at the 2-ng level in
      dot blots of tissue extracts.

PMID- 7519835
TI  - A general purification procedure for chemically synthesized oligoribonucleotides.
AB  - A general procedure for the purification of chemically synthesized
      oligoribonucleotides is reported. Purification based on the use of a single
      reverse-phase HPLC column with buffer systems of differing ion-pairing capacity
      is described. These methods have been applied to the preparation of a series of
      RNAs which range in size from 10 to 46 nucleotides. The yields obtained are high,
      up to 53% (based on isolated product compared to those obtained from final trityl
      assay). The purity of the isolated material is 96-99%. Thus with this general
      procedure, milligram quantities of extremely pure RNA can be efficiently
      obtained.

PMID- 7519837
TI  - Is aprotinin worth the risk in total hip replacement?

PMID- 7519836
TI  - Evidence for direct actions of general anesthetics on an ion channel protein. A
      new look at a unified mechanism of action.
AB  - BACKGROUND: Ion permeation through the nicotinic acetylcholine receptor channel
      is inhibited by general anesthetics. This inhibition could be mediated either by
      binding of anesthetic molecules to the channel protein itself or by the effects
      of anesthetics on the lipid environment of the protein. METHODS: Patch clamp
      recording techniques were used to investigate the effects of ether and propofol
      on acetylcholine receptor channels in outside-out patches from BC3H-1 cells. The
      kinetic and conductance properties of single channels were measured. A rapid
      perfusion system was used to make rapid changes in anesthetic concentration
      during patch clamp recording to determine the kinetics of inhibition by
      anesthetics. RESULTS: Ether, isoflurane (results from previous studies), and
      propofol produce distinct kinetic patterns of single acetylcholine receptor
      channel activity. Ether reduces the apparent current amplitude of channels,
      isoflurane induces flickering channel activity and propofol merely decreases the
      open time of the channel. The kinetics of inhibition are also different for these
      anesthetics. Ether (< 40 microseconds) is faster than isoflurane (300-600
      microseconds) which is faster than propofol (> or = 2 ms). CONCLUSIONS: These
      diverse patterns can be interpreted in terms of a unitary mechanism in which the
      anesthetics interact directly with the channel protein. Each anesthetic is
      considered to bind to a site on the protein (perhaps, but not necessarily within
      the pore of the channel) and interrupt the flow of ions through the pore.
      Anesthetics have access to this inhibitory binding site even when the gate of the
      channel is closed. The pattern of channel activity induced by an anesthetic is
      determined by the frequency and duration of binding events.

PMID- 7519838
TI  - Ichthyosis Curth-Macklin: a new sporadic case with immunohistochemical study of
      keratin expression.

PMID- 7519840
TI  - [An uncommon site of malignant germ cell tumor secreting alpha fetoprotein: the
      posterior mediastinum].
AB  - BACKGROUND: While germ cell tumors generally occur in the gonads, they may also
      appear at other sites, from the sacrococcygeum area to the central nervous
      system. This report describes a case of such a tumor in the posterior mediastinum
      that developed intraspinally in a dumb-bell fashion. CASE REPORT: A 2 1/2 year
      old girl was admitted for abdominal tenderness, gait disturbance and fever.
      Clinical examination showed spastic paraparesis and bladder dysfunction. Thoracic
      X-rays showed a left postero-superior mediastinal mass with rib erosion. MRI
      showed that this mass had developed intraspinally between the intervertebral
      foramina and caused spinal cord compression at T4, T5, T6. The tumor was not
      calcified. Surgical resection via laminectomy was performed in emergency, but the
      T5 root had to be excised. Pathologic examination showed histologic features of
      yolk sac carcinoma; the serum alpha-foetoprotein was elevated (12, 400 IU/ml).
      The patient was given chemotherapy for 6 months and is well 2 years later.
      CONCLUSION: Germ cell tumors may appear in unusual sites. They can be identified
      by measuring biological markers, and this avoid primary surgery.

PMID- 7519841
TI  - Choroidal neovascularization in black patients.
AB  - OBJECTIVE: To characterize choroidal neovascularization (CNV) in black patients
      examined at a retinal disease referral center. DESIGN: Retrospective review of
      the medical records of all patients diagnosed as having CNV to identify black
      patients with CNV. SETTING: Single tertiary retinal referral center that included
      four ophthalmologists. PATIENTS: All patients diagnosed as having CNV between
      April 1990 and October 1992. MAIN OUTCOME MEASURES: Prevalence, demographic
      information, fundus photographic and fluorescein angiographic characteristics,
      natural history, and response to laser photocoagulation of CNV in black patients.
      RESULTS: Black patients comprise 15% of all patients seen at this center. Of 1725
      patients identified as having CNV who were seen at the center during a 2.5-year
      period, only 25 were black (1.4%). In these patients, CNV was associated with a
      variety of retinal diseases, the most frequent being age-related macular
      degeneration. The average age of the study group was 54 years, women outnumbered
      men 2:1, and 13 of the patients developed bilateral lesions. Twelve of the 38
      lesions were extrafoveal on presentation, and five of these were peripapillary.
      In the laser-treated eyes, recurrence of CNV was frequent and associated with
      visual loss. CONCLUSIONS: Choroidal neovascularization seems to be rare in blacks
      among a retinal disease referral center population. The overall presentation,
      natural history, and response to laser treatment seems to be similar to that of
      white patients. No feature of CNV in black patients was identified that would
      suggest that results of randomized clinical trials of laser photocoagulation for
      CNV are not valid for these patients.

PMID- 7519842
TI  - Symptomatic choroidal neovascularization in blacks.
AB  - OBJECTIVE: To acquire descriptive clinical information regarding choroidal
      neovascularization (CNV) in black Americans. DESIGN: Retrospective review of 1308
      fluorescein angiograms obtained during a 4-year interval. Color photographs and
      clinical records of all black patients with angiographically apparent CNV were
      subsequently reviewed. SETTING: Retina service of an inner-city county hospital
      in Atlanta, Ga, serving a predominantly black population. RESULTS: Thirty blacks
      with CNV (36 of 59 eyes) were identified, 26 (87%) of whom were female. Active,
      exudative neovascularization was present in at least one eye of 21 patients
      (70%). Patients were assigned to one of four diagnostic groups for analysis.
      Group 1 was made up of 13 patients (43%) with age-related macular degeneration
      with CNV. Women outnumbered men 5.5:1. Choroidal neovascularization was
      peripapillary in seven (54%) of these 13 patients. Group 2 was made up of six
      patients (20%) with idiopathic CNV, which was peripapillary in all eyes. Group 3
      consisted of three women (10%) with idiopathic polypoidal choroidal vasculopathy.
      Group 4 was composed of eight patients (27%) with secondary CNV. The CNV was
      peripapillary in three (33%) of nine eyes, and women outnumbered men 7:1.
      CONCLUSIONS: The spectrum of neovascular maculopathy in blacks in the current
      study differed from that typically seen in whites, both clinically and
      demographically. Clinically, CNV was most commonly juxtapapillary (13 [68%] of 19
      patients) and unilateral (12 [92%] of 13 patients) among the age-related macular
      degeneration and idiopathic groups, while six (20%) of 30 patients (all older
      than 50 years) had CNV in the absence of drusen or other known predisposing
      conditions. Disciform-stage CNV in both groups was associated with a greater
      degree of pigment proliferation than that typically noted in whites.
      Demographically, female predominance (87% overall) was dramatic compared with
      prior studies.

PMID- 7519839
TI  - A subgroup of patients with chronic pancreatitis overexpress the c-erb B-2
      protooncogene.
AB  - OBJECTIVE: Chronic pancreatitis (CP) is a chronic condition associated with
      pancreatic fibrosis. A small subgroup of patients with CP develop enlargement of
      the head of the pancreas (EHP). This study examined some of the mechanisms that
      may lead to the development of EHP. SUMMARY BACKGROUND: The c-erb B-2
      protooncogene encodes a 185-kDa transmembrane growth factor receptor (p185) that
      regulates cell growth and differentiation. METHODS: The authors analyzed c-erb B
      2 expression in samples obtained from the head of the pancreas from 26 patients
      with CP (5 women, 21 men) using immunohistochemical and molecular technique. A
      diagnosis of CP with EHP was made when the vertical pancreatic head diameter was
      greater than 4 cm (14 patients), as determined by contrast-enhanced computed
      axial tomography scan. Pancreatic tissues from 15 healthy organ donors served as
      control subjects. RESULTS: In all patients without EHP and in the healthy control
      subjects, p185 immunoreactivity was present at low levels. In contrast, strong
      p185 immunoreactivity was observed in acinar and ductal cells in all patients
      with EHP. By in situ hybridization, c-erb B-2 messenger ribonucleic acid (mRNA)
      grains were expressed at high levels in patients with CP with EHP in both ductal
      and acinar cells. Northern blot analysis demonstrated a 4.5-fold increase (p <
      0.001) in c-erb B-2 mRNA levels in patients with EHP compared with patients
      without EHP and healthy control subjects. Southern blot analysis did not reveal c
      erb B-2 gene amplification or rearrangement. CONCLUSIONS: These findings indicate
      the c-erb B-2 is not overexpressed in most patients with CP. However, its
      overexpression in patients with CP with EHP suggest that c-erb B-2 may contribute
      to the pathophysiologic processes that lead to pancreatic head enlargement.

PMID- 7519843
TI  - Beta HCG levels after conservative treatment of ectopic pregnancy: is a plateau
      normal?
AB  - In 32 women with unruptured tubal ectopic pregnancies we undertook conservative
      laparoscopic treatment [local injection of 20 mg methotrexate (n = 18), laser
      salpingotomy (n = 14)]. The results of serial quantitative beta HCG measurement
      were followed until either a negative level was reached or until rising levels
      necessitated alternative/additional therapy. Plateaued values of beta HCG were
      observed in both the successful (n = 16) and the unsuccessful cases (n = 5). To
      test the hypothesis that daily variation in the assay could account for some or
      all of the observed plateaued results in successful cases, the sera were retested
      serially on the same 'run'. In only one case did laboratory variation account for
      the observed plateau. The clinical implications of the findings are discussed. We
      conclude that serially monitored beta HCG results after conservative treatment of
      ectopic pregnancy may show plateaued values without indicating failure of
      treatment.

PMID- 7519844
TI  - Persistent ectopic pregnancy after conservative management successful treatment
      with single-dose intramuscular methotrexate.

PMID- 7519846
TI  - Conformation and self-association of the peptide hormone substance P: Fourier
      transform infrared spectroscopic study.
AB  - Fourier-transform i.r. (f.t.i.r.) spectroscopy has been applied to the study of
      the conformational properties of substance P in aqueous solution. Spectra were
      obtained in the presence of lipid membranes and Ca2+ to assess the role of these
      factors in induction of the active conformation of the peptide. In aqueous
      solution substance P was found to be predominantly unstructured at physiological
      p2H, where the lack of long-range order is probably related to charge repulsion
      along the peptide chain. However, substance P aggregated in aqueous solution at
      p2H > 10.0. Little or no induction of secondary structure was seen on addition of
      the peptide to negatively charged bilayers, suggesting that interaction with a
      membrane surface does not play an important role in the stabilization of the
      active conformation of the peptide. In fact, substance P was found to aggregate
      in the presence of charged lipids, which would tend to hinder rather than enhance
      interaction with the receptor. We propose a model for the aggregation of
      substance P at the bilayer surface, based on our studies of the effect of p2H and
      lipid/peptide ratio on spectra. Addition of Ca2+ had no effect upon the secondary
      structure of the peptide or on its interactions with membranes.

PMID- 7519845
TI  - Inhibition of the differentiation of human myeloid cell lines by redox changes
      induced through glutathione depletion.
AB  - We have investigated the effect of redox changes in vivo on the differentiation
      of two human myeloid cell lines, HL-60 and KG-1. The glutathione-depleting agent
      diethyl maleate (DEM) prevented the development of differentiated features in
      response to phorbol esters, including adherence of the cells to plastic surfaces
      and repression of the myeloperoxidase and CD34 genes. Moreover, DEM abolished
      phorbol 12-myristate 13-acetate-induced activation of the transcription factors
      AP-1 and Egr-1, suggesting that inhibition of differentiation may be due, at
      least in part, to redox modifications of these proteins.

PMID- 7519847
TI  - The catalytic subunit of phosphatidylinositol 3-kinase is a substrate for the
      activated platelet-derived growth factor receptor, but not for middle-T antigen
      pp60c-src complexes.
AB  - The interaction of phosphatidylinositol 3-kinase (PI 3-K) with polyoma-virus
      middle-T antigen-pp60c-src (mT:cSrc) complexes and with the platelet-derived
      growth factor (PDGF) receptor has been investigated. Firstly, we undertook
      reconstitution studies, using proteins derived from a baculovirus expression
      system. The p110 catalytic subunit of the PI 3-K associated with tyrosine kinases
      only when complexed with the p85 alpha regulatory subunit. Both p85 alpha and
      p110 were substrates of the PDGF receptor. In contrast, only the p85 alpha
      subunit was detectably phosphorylated when PI 3-K was associated with mT:cSrc.
      Secondly, we studied PI 3-K in mammalian cells. In mT-antigen-transformed NIH-3T3
      cells neither p85 alpha nor p110 was phosphorylated on tyrosine residues in vivo,
      even though p85 alpha was a substrate in kinase assays in vitro. In quiescent NIH
      3T3 cells, PI 3-K showed detectable activity in vitro; PDGF stimulation resulted
      in a rapid and transient association of PI 3-K with the receptor, which was
      correlated with a transient increase in intrinsic P13-K activity (approx. 2
      fold). The activated PDGF receptor phosphorylated p110 in vitro, at one major
      site. In vivo, PDGF stimulation induced tyrosine phosphorylation of p110 that
      persisted for at least 1 h after stimulation. Immunodepletion of the PDGF
      receptor from stimulated cell lysates showed that p110 was released from the
      receptor in a tyrosine-phosphorylated form. From these results we conclude that
      (i) the mT:cSrc complex and the PDGF receptor differ in their association with PI
      3-K activity, (ii) PDGF receptor appears to activate PI 3-K in vivo both by
      relocation of the enzyme and by stimulation of its intrinsic activity, and (iii)
      tyrosine phosphorylation of the p110 subunit by the PDGF receptor may play a role
      in PI 3-K regulation in some circumstances.

PMID- 7519849
TI  - Isolation and characterization of fibronectin-alpha 1-microglobulin complex in
      rat plasma.
AB  - Molecules containing the 28 kDa immunoregulatory protein alpha 1-microglobulin
      (alpha 1-m), also known as protein HC, were isolated from rat plasma or serum by
      immunoaffinity chromatography. Three molecular species were distinguished on the
      basis of nondenaturing PAGE. Two of these have been described previously:
      uncomplexed alpha 1-m, and the complex of alpha 1-m with alpha 1-inhibitor-3. The
      third species was analysed by denaturing PAGE, immunoblotting, proteinase
      digestion and N-terminal-sequence analyses, and shown to consist of a complex
      between alpha 1-m and fibronectin. This complex, with a mass of about 560 kDa,
      was resistant to dissociation in the presence of denaturants, but not in the
      presence of reducing agents in combination with denaturants, and we conclude that
      the two components are linked by disulphide bonds. About 60% of the total
      detectable plasma alpha 1-m exists as high-molecular-mass complexes distributed
      approximately evenly between fibronectin and alpha 1-inhibitor-3. Immunochemical
      analyses were used to determine the proportion of the total plasma pools of
      fibronectin and alpha 1-inhibitor-3 that circulate in complex with alpha 1-m.
      About 3-7% of the total plasma fibronectin from three different rat strains
      contained alpha 1-m, whereas 0.3-0.8% of the total plasma alpha 1-inhibitor-3
      contained alpha 1-m. Complexes were found at similar levels in plasma and serum,
      indicating that coagulation is not responsible for complex formation. Moreover,
      immunochemical analyses of human plasma revealed small amounts of alpha 1-m in
      complex with fibronectin and alpha 2-macroglobulin (an alpha 1-inhibitor-3
      homologue). The existence of a complex between alpha 1-m and fibronectin in rats
      and humans suggests a mechanism for the incorporation of the immunoregulatory
      molecule alpha 1-m into the extracellular matrix.

PMID- 7519848
TI  - Caffeine inhibits cytosolic calcium oscillations induced by noradrenaline and
      vasopressin in rat hepatocytes.
AB  - The effects of caffeine on agonist-induced changes in intracellular Ca2+
      concentration ([Ca2+]i) were studied in single fura 2-loaded cells and
      suspensions of rat hepatocytes. In single cells, caffeine (5-10 mM) inhibited
      [Ca2+]i oscillations induced both by noradrenaline (0.1 microM) and by
      vasopressin (0.1 nM). Caffeine shifted the dose-response curves of the [Ca2+]i
      rise induced by vasopressin (0.5 to 2 nM) and noradrenaline (from 80 to 580 nM)
      in suspensions of liver cells loaded with quin2. This inhibitory effect of
      caffeine was not due to inhibition of phosphodiesterase enzymes and elevation of
      cyclic AMP levels, because application of 3-isobutyl-1-methylxanthine, forskolin
      or 8-bromo cyclic AMP had no inhibitory effect on the intracellular Ca2+ rise
      induced by inositol 1,4,5-trisphosphate (InsP3)-dependent agonists. We
      demonstrate that the inhibitory effect of caffeine may result from at least three
      actions of caffeine: (1) inhibition of receptor-stimulated InsP3 formation; (2)
      inhibition of agonist-stimulated Ca2+ influx; and (3) direct inhibition of the
      InsP3-sensitive Ca(2+)-release channel.

PMID- 7519851
TI  - Investigation of antigen-antibody interactions using a soluble, non-support-bound
      synthetic decapeptide library composed of four trillion (4 x 10(12) sequences.
AB  - A decapeptide positional-scanning synthetic-peptide combinatorial library (PS
      SPCL) made up of four trillion (4 x 10(12) decapeptides was synthesized; its use
      is illustrated here for the study of a peptide-antibody interaction. This library
      was prepared by a chemical-mixture approach using a specific ratio of amino acids
      empirically determined to give approximately equimolar incorporation of each
      amino acid during each coupling step. Despite the immense number of decapeptides
      making up each peptide mixture [approx. 200 billion (2 x 10(11)], specific
      sequences having nanomolar affinities for a peptide-antibody interaction could be
      readily identified. Upon screening this decapeptide PS-SPCL in this well
      characterized system, the known six-residue antigenic-determinant sequence was
      found, with the most specific residues appearing to 'walk through' the ten
      positions of the peptide library. More importantly, it appears that antibody
      recognition in this system is stronger when the antigenic determinant is located
      at the C-terminus of the decapeptide library. Individual decapeptides
      corresponding to sequences derived from the most active peptide mixtures at each
      position were synthesized to confirm the results of the screening; 15 peptides
      were found to have IC50 values between 0.6 and 9.5 nM, four of which were found
      to be 5-10 times more active than the known six- and 13-residue control peptides.
      These results further illustrate the power of the positional-scanning peptide
      library concept, and extend its practical range to a decamer library composed of
      four trillion (4 x 10(12) decapeptides.

PMID- 7519850
TI  - Tetrafibricin, a novel non-peptide fibrinogen receptor antagonist, induces
      conformational changes in glycoprotein IIb/IIIa.
AB  - Arg-Gly-Asp (RGD) is an amino acid sequence in fibrinogen recognized by platelet
      glycoprotein (GP) IIb/IIIa. Recently, it was found that RGD peptide binding to
      GPIIb/IIIa leads to conformational changes in the complex that are associated
      with the acquisition of high-affinity fibrinogen-binding function. In this study,
      we found that tetrafibricin, a novel non-peptidic GPIIb/IIIa antagonist, induced
      similar conformational changes in GPIIb/IIIa as did RGD peptides. Tetrafibricin
      increased the binding of purified inactive GPIIb/IIIa to immobilized pl-80, a
      monoclonal antibody that preferentially recognizes ligand-occupied GPIIb/IIIa.
      Exposure of the pl-80 epitope by tetrafibricin was also observed on resting human
      platelets by flow cytometry. On intact platelets, the conformational changes
      transformed GPIIb/IIIa into a high-affinity receptor for fibrinogen and triggered
      subsequent platelet aggregation. Tetrafibricin is the first non-peptidic
      GPIIb/IIIa antagonist reported that has the capacity to induce conformational
      changes in GPIIb/IIIa.

PMID- 7519853
TI  - Agonist-induced down-regulation of platelet-activating factor receptor gene
      expression in U937 cells.
AB  - Prolonged exposure (8-24 h) of human promonocytic U937 cells to 100 nM 1-O
      hexadecyl-2-N-methylcarbamyl-sn-glycero-3-phosphocholine (carbarmyl-PAF), a non
      metabolizable analogue of platelet-activating factor (PAF), reduced the numbers
      of PAF receptors by 50-75%, as determined by the radioligand-binding assay. To
      clarify whether the down-regulation of receptor numbers is due to decreased
      expression level of the PAF-receptor gene, the effect of carbamyl-PAF on the
      steady-state level of PAF-receptor mRNA was examined by a highly sensitive
      reverse-transcriptase PCR method. A 50% decline in the level of PAF-receptor mRNA
      was observed in U937 cells pretreated with 100 nM carbamyl-PAF for 24 h. The
      effect of carbamyl-PAF was dose-dependent, with an EC50 value around 10 nM. PAF
      receptor antagonist, SRI-63675, was able to attenuate the effect of carbamyl-PAF.
      Furthermore lysoPAF, at 1 uM, was unable to induce a significant decrease in PAF
      receptor mRNA after incubation for 24 h, indicating that the effect of carbamyl
      PAF was specific. The half-life of the PAF-receptor mRNA measured in the presence
      of actinomycin D was unaffected by carbamyl-PAF treatment. In contrast, nuclear
      run-off experiments demonstrated that the transcription rate of the PAF-receptor
      gene in carbamyl-PAF-treated cells was about 65% of that in control cells. These
      results suggest that the PAF receptor in U937 cells is subject to down-regulation
      by agonist, at least partly, at the transcriptional level.

PMID- 7519852
TI  - Epitope mapping of monoclonal antibodies to the paired helical filaments of
      Alzheimer's disease: identification of phosphorylation sites in tau protein.
AB  - Tau is a neuronal phosphoprotein the expression of which is developmentally
      regulated. A single tau isoform is expressed in fetal human brain but six
      isoforms are expressed in adult human brain, with the fetal isoform corresponding
      to the shortest adult isoform. Phosphorylation is also developmentally regulated,
      as fetal tau is phosphorylated at more sites than adult tau. In Alzheimer's
      disease, the six adult tau isoforms become hyperphosphorylated and form the
      paired helical filament (PHF), the major fibrous component of the neurofibrillary
      lesions. One way to identify phosphorylated sites in tau is to use antibodies
      that recognize phosphorylated residues within a specific amino acid sequence. We
      here characterize the two novel phosphorylation-dependent anti-tau antibodies
      AT270 and AT180 and identify their epitopes as containing phosphorylated Thr-181
      and Thr-231 respectively. With these antibodies we show that these two threonine
      residues are partially phosphorylated in fetal and adult tau and almost fully
      phosphorylated in PHF tau. This result contrasts with previous studies of Ser-202
      and Ser-396 which are partially phosphorylated in fetal tau, unphosphorylated in
      adult tau but almost fully phosphorylated in PHF tau.

PMID- 7519854
TI  - Involvement of membrane bleomycin-binding sites in bleomycin cytotoxicity.
AB  - The authors have recently shown the existence of bleomycin (BLM)-binding sites at
      the surface of DC-3F cells. In order to study the involvement of these sites in
      the sensitivity of the cells to bleomycin several BLM-resistant cell lines from
      DC-3F cells were analysed. These mutants were obtained by electrotransfection of
      the Sh ble gene (D/BlmI cells) or the Sh ble-beta Gal fusion gene (D/BlmII cells)
      and/or by continuous culture in the presence of BLM (D/BlmIR and D/Blm40 cells).
      The resistance levels of the D/BlmII and D/Blm40 cells were 50- and 22-fold,
      respectively, determined at the EC50 level. The D/BlmI cells were only 2-fold
      resistant, whereas D/BlmIR cells were so resistant that almost no cytotoxicity
      was detected up to 200 microM BLM external concentration. Electropermeabilization
      was used in an attempt to bypass the plasma membrane of the cells and permit the
      distinction between internal resistance and membrane resistance. The former was
      observed when the products of the transfected genes were present. With respect to
      membrane resistance, differences were detected in the number of BLM-binding sites
      in several mutant cell lines, which could account for the differences in cell
      sensitivity to BLM. This suggests that the BLM-binding sites found at the cell
      surface may play a crucial role in BLM internalization and consequently in its
      cytotoxicity.

PMID- 7519856
TI  - Expression of the choroid plexus sodium-nucleoside cotransporter (N3) in Xenopus
      laevis oocytes.
AB  - In this study, we determined the expression of the Na(+)-nucleoside cotransporter
      (N3) in Xenopus laevis oocytes injected with poly(A)+ RNA isolated from rabbit
      choroid plexus. The Na(+)-dependent thymidine uptake in poly(A)+ RNA-injected
      oocytes (maximum 4-5 days after injection) increased proportionally with the
      injected dose of poly(A)+ RNA. Uptake was enhanced 4- to 5-fold in oocytes
      injected with 40 ng poly (A)+ RNA in comparison to water-injected oocytes.
      Consistent with the N3 Na(+)-nucleoside cotransporter, Na(+)-dependent thymidine
      uptake in poly(A)+ RNA-injected oocytes was inhibited significantly by both
      purine and pyrimidine nucleosides, but not by dideoxycytidine, a nucleoside
      analog modified on the ribose ring. These data suggest for the first time that
      the N3 Na(+)-nucleoside cotransporter in rabbit choroid plexus can be expressed
      in X. laevis oocytes.

PMID- 7519855
TI  - Effect of hydrogen peroxide and catalase on rat cerebellum nitric oxide synthase.
AB  - The effect of H2O2 and catalase on isolated rat cerebellum nitric oxide (NO)
      synthase activity was determined by measuring the conversion of L-[3H]arginine to
      L-[3H]citrulline. H2O2 (1-5 mM) markedly increased NO synthase activity in the
      presence of endogenous catalase (72 +/- 4 U/mL). This effect of H2O2 was further
      increased by exogenous catalase (200 U/mL). Exogenous catalase (0.1 to 1000 U/mL)
      by itself had no significant effect on NO synthase activity. Nitroblue
      tetrazolium chloride, an electron acceptor, inhibited NO synthase activity in a
      concentration-dependent manner. This study suggests that H2O2 is not directly
      involved in NO synthesis and that the H2O2/catalase stimulation of NO synthase
      activity may be due to the excess oxygen produced by the H2O2/catalase system.

PMID- 7519857
TI  - [Selectin receptors. 1. Synthesis of SiaLe(a) and SiaLe(x) tetrasaccharides and
      their polymeric conjugates].
AB  - Spacer-armed tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Fuc alpha 1- 4)GlcNAc
      sp (SiaLe(a), sp = OCH2CH2CH2NH2) was synthesized from 6-BnGlcNAc-sp with 6
      BnAc3GalSEt, Bn3FucSEt, and Ac4Neu5AcSEt methyl ester as glycosyl donors. The
      final glycosylation of the trisaccharide bearing unprotected 2-, 3-, and 4
      hydroxyls of galactose moiety was promoted with NIS-TfOH in MeCN, yield of alpha
      sialoside being 48% (29% as the NGlcNAc-SEt derivative). A mixture of beta
      connected (2-3) and (2-4) lactones was obtained as a side product (30%).
      Tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-sp (SiaLe(x))
      was synthesized by a similar way starting from 6-Bn-3-MeOBnGlcNAc-sp; yield of
      alpha-sialylation was 74%, neither N-SEt nor beta-connected lactones were
      isolated. Condensation of the spacered tetrasaccharides with poly(4
      nitrophenylacrylate) gave N-substituted polyacrylamide-type polymers.
      Biotinylated probes and polymers modified with phosphatidylethanolamine (strong
      immunogens) were also obtained. The unsubstituted and labelled polymeric
      derivatives were used for studying selectins and other lectins, as well as
      production and epitope characterization of monoclonal antibodies against
      sialooligosaccharides.

PMID- 7519858
TI  - [Selectin receptors. 2. Synthesis of HSO3-3'Le(a)--a sulfated ligand of the cell
      adhesion molecule, E-selectin].
AB  - HSO3-3'Gal beta 1-3(Fuc alpha 1-4)GlcNAc beta 1-O(CH2)3NH2 was synthesized by
      selective sulfation (Py.SO3/Py, O degree C) of a protected trisaccharide Lea
      derivative bearing unsubstituted hydroxyls at C2 and C3 of the galactose moiety,
      BdGal beta 1-3(Bn3Fuc alpha 1-4)6-BnGlcNAc beta 1-O(CH2)3NHCOCF3, followed by
      convenient deprotection. A monosaccharide derivative, HSO3-3Gal beta 1
      O(CH2)3NH2, was also obtained in a similar way. Coupling of the aminopropyl
      glycosides with poly(4-nitrophenylacrylate) gave rise to polyacrylamide (PAA)
      conjugates; biotinylated probes of the Sug-PAA-biotin type were obtained as well.

PMID- 7519859
TI  - Serum levels of soluble adhesion molecules intercellular adhesion molecule 1,
      vascular cell adhesion molecule 1, and E-selectin in patients with Wegener's
      granulomatosis. Relationship to disease activity and relevance during followup.
AB  - OBJECTIVE: To assess the value of measuring serum levels of soluble intercellular
      adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAMP
      1), and soluble E-selectin for monitoring disease activity in Wegener's
      granulomatosis (WG). METHODS: A sandwich enzyme-linked immunosorbent assay was
      used to measure levels of soluble adhesion molecules at the time of diagnosis in
      22 consecutive patients with WG, in 12 WG patients studied serially prior to
      disease relapse, at the time of upper airways infection in 18 patients with
      inactive WG, and in 57 controls. Disease activity was assessed by disease
      activity score and C-reactive protein levels. RESULTS: At diagnosis of WG, sICAM
      1 and sVCAM-1 levels were significantly elevated and correlated with disease
      activity. At the time of relapse, a significant increase in all 3 soluble
      adhesion molecules was found compared with levels at 6 months prior to relapse,
      but only sVCAM-1 levels were significantly elevated compared with those in
      controls. Levels of soluble adhesion molecules at the time of relapse did not
      differ from those measured during an upper airways infection without disease
      activity. CONCLUSION: Elevated serum levels of sICAM-1 and sVCAM-1 can be found
      in active WG and correlate with disease activity. However, their clinical
      relevance for followup is limited due to lack of sensitivity and specificity for
      WG disease activity.

PMID- 7519860
TI  - Educational objectives for medical training in the care of the terminally ill.
AB  - BACKGROUND: Palliative medicine is developing as a distinct clinical discipline
      worldwide. The U.S. literature describes goals for education in palliative
      medicine, yet this literature lacks validated educational objectives. METHOD: To
      develop and validate appropriate educational objectives for medical training in
      the care of the terminally ill, 200 randomly selected members of the Academy of
      Hospice Physicians were asked in 1992 to evaluate 39 educational objectives by an
      item-objective congruence procedure. Each objective was rated as -1
      (inappropriate), 0 (unsure), or 1 (appropriate). RESULTS: Of the 200 members
      surveyed, 127 (64%) responded. Of the 39 objectives, 34 were considered valid,
      with a mean score of > or = .8. The index of content validity was .87. The
      objectives not considered valid all dealt with nonmedical issues related to
      hospice or palliative care. CONCLUSION: This study validated 34 educational
      objectives for medical training in the care of the terminally ill. Training
      programs using these objectives, amended for specific audiences, should be
      included in the various levels of U.S. medical education.

PMID- 7519861
TI  - Epitope discovery using peptide libraries displayed on phage.
AB  - Peptides displayed on phage, which mimic continuous and discontinuous epitopes,
      can be selected using purified antibodies or preparations of polyclonal serum.
      This review describes recent advances in this field, discusses the application of
      phage-display technology to the diagnosis of human diseases, and presents new
      ideas for the preparation of vaccines directed against specific epitopes on a
      pathogen.

PMID- 7519862
TI  - Inventing and improving ribozyme function: rational design versus iterative
      selection methods.
AB  - Two major strategies for generating novel biological catalysts exist. One relies
      on our knowledge of biopolymer structure and function to aid in the 'rational
      design' of new enzymes. The other, often called 'irrational design', aims to
      generate new catalysts, in the absence of detailed physicochemical knowledge, by
      using selection methods to search a library of molecules for functional variants.
      Both strategies have been applied, with considerable success, to the remodeling
      of existing ribozymes and the development of ribozymes with novel catalytic
      function. The two strategies are by no means mutually exclusive, and are best
      applied in a complementary fashion to obtain ribozymes with the desired catalytic
      properties.

PMID- 7519863
TI  - Production and selection of mutants of Leuconostoc mesenteroides constitutive for
      glucansucrases.
AB  - After chemical mutagenesis using ethyl methane sulfonate, we isolated mutants
      constitutive for glucansucrases from Leuconostoc mesenteroides NRRL B-512FM, B
      1142, and B-1355. Those mutants produced glucansucrases when grown on D-glucose
      as well as on sucrose. They produced higher glucansucrase activities (3 to 22
      times) when grown on D-glucose than the parent strains grown on sucrose.
      Glucansucrases from mutants B-1355C and B-1142C grown on glucose formed glucans
      that were highly resistant to Penicillium dextranase hydrolysis. Mutant B-512FMC
      dextransucrase formed the same kind of dextran as the parent strain; however, it
      showed higher thermal stability, even when dextran was absent.

PMID- 7519864
TI  - Flow cytometry studies of recombinant Escherichia coli in batch and continuous
      cultures: DNA and RNA contents; light-scatter parameters.
AB  - Flow cytometry has been used to study the contents of macromolecular compounds
      and light-scatter parameters in batch and continuous cultures of a recombinant
      Escherichia coli strain that forms protein inclusion bodies. Changes in relative
      DNA and RNA contents and cell mass as estimated by forward-angle light scatter
      were detected and tightly correlated in batch culture. In addition, heterogeneity
      of wide-angle light scatter (WALS), which we related to the presence of cellular
      inclusion bodies, was observed. In contrast, the relative RNA content and cell
      mass did not change during continuous culture, and homogeneity of WALS was found.
      In addition, unexpected changes in relative DNA content were observed after 67 h
      of culture, indicating a change in bacterial physiology.

PMID- 7519865
TI  - Role of transepidermal and transfollicular routes in percutaneous absorption of
      steroids: in vitro studies on human skin.
AB  - Percutaneous absorption theoretically comprises two components: the
      transepidermal and the transfollicular routes. The aim of the present work was to
      confirm this hypothesis in the human skin by comparing the in vitro percutaneous
      absorption of four steroids through scar skin without hair follicles and
      sebaceous glands and through normal adjacent skin from abdominal or mammary
      plasties. In all cases, the absorption of the four steroids was significantly
      higher in normal skin than in scar skin. The cumulative percentages of
      progesterone and testosterone after 8 h of application were, respectively, 3.1-
      and 2.4-fold higher in normal skin than in scar skin. After 24 h of application,
      the cumulative percentages of estradiol and hydrocortisone were 1.7- and 2.4-fold
      higher in normal skin than in scar skin. At the end of the experiments, the
      quantities of drugs remaining in the skin after 8 or 24 h of application were the
      same in normal skin and in scar skin except for progesterone for which they were
      2-fold greater in normal than in scar skin. In each case, a histological
      characterization of the scar skin was made in comparison with the normal adjacent
      skin. The main modifications observed on scar skin were the following: absence of
      hair follicles and sebaceous glands, thinning of the collagenous fibers with
      parallel orientation to the dermoepidermal junction and decrease in the number or
      disappearance of the elastic fibers. These experiments confirmed that human skin
      appendages, hair follicles and sebaceous glands, constitute a route of
      penetration for steroids and thus probably for other chemicals of similar
      molecular weight and properties.

PMID- 7519868
TI  - Deletion mapping reveals two regions of chromosome 8 allele loss in colorectal
      carcinomas.
AB  - Colorectal carcinogenesis is associated with the accumulation of genetic changes
      involving both dominant oncogenes and tumor suppressor genes. Although at least
      four different genes have been implicated in the process, the detection of allele
      loss from other regions of the genome suggests the involvement of additional
      genes. The short arm of chromosome 8 is one of these regions; loss of
      heterozygosity occurs at rates ranging from 30 to 50%. To define the region of
      common deletion containing the putative tumor suppressor gene, we analyzed a
      series of 87 carcinomas for allele loss in different regions of the short arm of
      chromosome 8 by using Southern blot analysis and a panel of polymorphic probes.
      We found allele loss in 33% of our cases, which involves two separate regions,
      one in the p-terminal region of the chromosome, 8p23.1-pter, where 45% of
      informative cases demonstrated loss, and the other in the mid-p region, at 8p21,
      where 31% of cases showed allele loss. No tumors showed loss of heterozygosity
      for both regions. These findings suggest the presence of two discrete genes
      related to colorectal carcinogenesis on the short arm of chromosome 8.

PMID- 7519867
TI  - Expression of tumour necrosis factor alpha and its receptors in carcinoma of the
      breast.
AB  - The expression of tumour necrosis factor alpha (TNF-alpha) and its two distinct
      receptors, TNF-R p55 and TNF-R p75, was assessed by immunocytochemistry in 28
      primary breast cancer and three reduction mammoplasty specimens ('normal' breast
      tissue). Expression of TNF-alpha or TNF-R p75 was not detectable in normal breast
      tissue or in non-malignant breast tissue adjacent to the tumours. By contrast,
      TNF-R p55 was expressed by occasional stromal cells in normal tissue. TNF-alpha
      was expressed focally in 50% of the tumours studied, being largely localised to
      macrophage-like cells in the stroma. TNF-R p55 was expressed by a population of
      stromal cells in all the tumours examined, and a varying proportion of neoplastic
      cells in 75% of these tissues. TNF-R p75 was detected in about 70% of the
      tumours, immunoreactivity being confined mainly to cells in the stroma. In this
      preliminary study there was no association between the above cytokine parameters
      and such measures of tumour biology as lymph node status, tumour grade,
      proliferative activity or degree of angiogenesis. However, there was a
      correlation between the expression of TNF-R p55 by blood vessels and the number
      of leucocytes present.

PMID- 7519869
TI  - Myelodysplastic syndrome transforming to acute promyelocytic-like leukemia with
      trisomy and rearrangement of chromosome 11.
AB  - Variants of the t(15;17)(q22;q12-q21) chromosomal rearrangement associated with
      acute promyelocytic leukemia (APL) have been previously described and they
      frequently involve either chromosome 15 and/or 17. Previously we reported a rare
      variant t(11;17). We now describe two patients with myelodysplastic syndrome
      (MDS) that transformed to APL-like leukemia. Both had trisomy 11 at the diagnosis
      of APL-like leukemia. Following treatment for APL, patient 1 reverted to MDS and
      showed a normal karyotype. When leukemia recurred, his bone marrow karyotype was
      47,XY,t(4;11), +11,der(22)t(1;22). Both patients were treated with all-trans
      retinoic acid (ATRA) for APL for 5 weeks, but failed to respond. The karyotype of
      patient 1 after ATRA treatment was 46,XY,t(4;11); the trisomy 11 had been lost
      and the bone marrow was replaced with immature myeloblasts without promyelocytes.
      In patient 2, the karyotype remained the same as at diagnosis, i.e., 47,X,-Y,dir
      ins(4;7),del(5), +6,del(7), +8, + 11,-18. Molecular analysis by reverse
      transcriptase PCR analysis showed the presence of wild type retinoic acid
      receptor alpha (RARA) and the absence of the PML-RARA chimeric gene associated
      with t(15;17). Additional analysis of PLZF, a new zinc finger gene associated
      with t(11;17), also showed the absence of this hybrid gene. These data support
      the concept that APL is a heterogeneous disorder and that variants with
      chromosome 11 rearrangement exist that do not respond to ATRA.

PMID- 7519870
TI  - Deletion of a common region on the long arm of chromosome 6 in acute
      lymphoblastic leukaemia.
AB  - We have characterised a region of deletion on the long arm of chromosome 6 (6q)
      in six cases of acute lymphoblastic leukaemia, by fluorescence in situ
      hybridisation, using a series of YAC clones which map to 6q. Conventional
      cytogenetic analysis of four of these cases had been interpreted as showing
      terminal deletions of 6q. We demonstrated by FISH that in all cases the deletions
      were interstitial. D6S246 (6q16.3) was the only marker which was missing in all
      six cases, indicating a common region of deletion between the markers M6P1 at
      6q14-15 and FYN at 6q21. Our results suggest the presence of a tumour suppressor
      gene within this interval.

PMID- 7519866
TI  - Monoamine oxidase-A: pharmacodynamics in humans of moclobemide, a reversible and
      selective inhibitor.
AB  - 1. Single oral doses of 300, 450 and 600 mg moclobemide, a monoamine oxidase type
      A inhibitor, were administered in a cross-over design to eight healthy male
      volunteers. Plasma concentrations of the parent drug and of two monoamine
      metabolites (3,4-dihydroxyphenylglycol DHPG from noradrenaline; 5-hydroxy
      indoleacetic acid 5HIAA from serotonin) were measured over time. 2. A
      physiological pharmacokinetic-pharmacodynamic model was used to describe MAO-A
      inhibition as reflected in the alterations of monoamine metabolites. Population
      values for the model parameters were obtained by a two-stage method allowing for
      repeated dosing per subject. 3. Even at the lowest dose an effect of moclobemide
      on plasma DHPG and 5HIAA concentrations was detectable in most subjects for up to
      24 h. In contrast to DHPG, 5HIAA formation was only partially suppressed by
      moclobemide (maximum fractional extent of enzyme inhibition Imax: 0.57, CV 26%)
      suggesting the existence of 5HIAA formation pathways independent of those
      inhibitable by moclobemide. 4. Plasma moclobemide concentrations associated with
      50% of maximum enzyme inhibition (IC50) were in the range of 100 (IC50,5HIAA at
      300 mg) to 400 micrograms l-1 (IC50,DHPG at 600 mg).

PMID- 7519871
TI  - There may be two tumor suppressor genes on chromosome arm 1p closely associated
      with biologically distinct subtypes of neuroblastoma.
AB  - We studied loss of heterozygosity (LOH) on chromosome arm 1p in 108
      neuroblastomas using 14 polymorphic DNA markers. One-hundred and four tumors with
      one or more informative loci; 21 (20%) of the 104 tumors showed LOH on 1p, and
      were classified into three groups on the basis of interstitial or terminal
      allelic loss, and presence or absence of LOH on 1p. Seven of the 21 tumors showed
      an interstitial deletion which encompassed a small region in 1p36 (group A), and
      the other 14 showed a terminal deletion which encompassed the region from 1pter
      to 1p32 (group B). Eighty-three tumors without LOH on 1p were classified as group
      C. The group A patients were mostly less than 12 months of age (6/7), were
      frequently found by a mass screening program for infants (5/7), had a tumor of
      non-adrenal origin, and rarely progressed to stage IV (1/7). Most group B
      patients were 12 months or older (11/14), were found clinically (11/14), had
      tumors of adrenal origin, and progressed to stage IV (10/14). Analysis of
      biologic characteristics in group C tumors suggested that they may comprise group
      A and B tumors. While all group A tumors were in the triploid range (3n) (4/4),
      most group B tumors were diploid (2n) or tetraploid (4n) (7/10). MYCN
      amplification was found in 8 group B tumors, but in none of group A tumors. Event
      free survivals of groups A, B, and C patients at 3 years were 86, 49, and 74%,
      respectively (P = 0.0287). These findings suggest that there may be two tumor
      suppressor genes on 1p which are closely associated with two biologically
      distinct subtypes of neuroblastoma.

PMID- 7519872
TI  - Identification of genetically aberrant cell lineages in Wilms' tumors.
AB  - Most Wilms' tumors contain several predominant cell types, of which a primitive
      blastemal population is often the most prominent. Other typical components
      include undifferentiated mesenchymal and epithelial cells, but it has not been
      demonstrated that these components are neoplastic. We used a combined cytogenetic
      and fluorescence in situ hybridization approach to determine the clonal
      relationship of different cell populations within six Wilms' tumors. Clonal
      numerical chromosome aberrations in three Wilms' tumors were found in blastemal
      cells, but not in mesenchymal cells. Loss of one WT1 allele in two other tumors
      was detected in both blastemal and mesenchymal cells. Tetrasomy 18 in a sixth
      case was observed in mesenchymal and epithelial cells; blastemal cells could not
      be evaluated in this tumor. These findings demonstrate that mesenchymal and
      epithelial cells in some Wilms' tumors are neoplastic. Different histologic
      components in some Wilms' tumors derive from a single chromosomally aberrant
      ancestor which is most likely to be the primitive blastemal cell.

PMID- 7519873
TI  - Malignant rhabdoid tumor of the kidney: involvement of chromosome 22.
AB  - Cytogenetic and molecular studies have demonstrated that involvement of 22q is a
      non-random finding in malignant rhabdoid tumors (MRTs) of the brain. We present
      an MRT of the kidney with the karyotype 47,XY, + i(1)(q10),
      der(8)t(8;22)(q12;q11.2),der(22)t(8;22)(q23 or q24.1;q11.2). This unbalanced
      reciprocal translocation was confirmed by fluorescence in situ hybridization
      (FISH) with chromosome-specific paints for chromosomes 8 and 22. Molecular
      analysis demonstrated a partial deletion of 22q in the BCR region at q11.2,
      strengthening the suspicion that this is a critical region for the initiation or
      progression of these highly malignant neoplasms. Establishing non-random
      cytogenetic changes in MRTs arising from the kidney may be of value in
      distinguishing these rare, but often fatal tumors from other renal neoplasms that
      mimic them histologically. The similarity in cytogenetic and molecular
      abnormalities between renal and extra-renal MRTs argues against the concept that
      extra-renal MRTs are only representative of a rhabdoid phenotype, rather than
      being true rhabdoid tumors.

PMID- 7519874
TI  - Loss of neurofibromin in adrenal gland tumors from patients with
      neurofibromatosis type I.
AB  - The neurofibromatosis type I gene encodes a protein, neurofibromin, which may
      function as a tumor suppressor gene product. Recent studies have demonstrated
      loss of neurofibromin in tumors from NF1 and non-NF1 patients, including
      neurofibrosarcomas, neuroblastomas and malignant melanomas. Since neurofibromin
      is expressed in the adrenal gland, six pheochromocytomas and one adrenal cortical
      tumor were examined for neurofibromin expression. In all seven tumors, no
      neurofibromin could be detected. Furthermore, loss of heterozygosity (LOH)
      analysis demonstrated that in one of the pheochromocytomas, reduction to
      homozygosity was observed for both 17p and 17q markers while the adrenal cortical
      tumor demonstrated LOH for only 17q markers. The frequent LOH surrounding the NF1
      locus and lack of neurofibromin expression in these tumors suggest that NF1 gene
      mutations may contribute to the development of adrenal gland neoplasms in
      patients with NF1.

PMID- 7519875
TI  - Chromosomal markers of immortalization in human breast epithelium.
AB  - We describe a series of five immortal breast cell lines that have emerged
      independently from diploid cultures from two individuals. We have karyotyped
      representative cultures of each of these lines prior to and at intervals after
      immortalization. Although considerable diversity of chromosomal aberration was
      found among the five lines, analysis of sublines has defined the chromosomal
      changes common for each immortalization. These changes differed both within and
      between the individual patient sources. Some common alterations were noted in
      lines from both patients, however, including loss of the short arm of chromosome
      20 and gain of 1q. We suggest that genes within these chromosomal regions
      contribute to spontaneous immortalization of human breast epithelium.

PMID- 7519876
TI  - Tumor progression in a giant cell type malignant fibrous histiocytoma of bone:
      clinical, radiologic, histologic, and cytogenetic evidence.
AB  - A malignant fibrous histiocytoma (MFH) of bone arising in the fibula of a 21-year
      old woman is described. Clinical, radiologic, and histologic findings
      demonstrated rapid tumor progression. Chromosomal analysis of the biopsy specimen
      showed great karyotypic heterogeneity, whereas the resection specimen four weeks
      later displayed a rather homogeneous karyotype. Both revealed a clonal
      t(14;22)(q11;p12). Several other clonal and non-clonal chromosomal aberrations
      were observed. Some of these were previously described in giant cell tumor of
      bone (GCTB) and may correlate with aggressive behavior, e.g., aberrations
      involving 8p11, 19q13, and 20q13. The change from karyotypic heterogeneity to
      relative homogeneity may be related to tumor progression. The chromosomal
      findings further suggest that the giant cell type of MFH of bone may be related
      to malignant GCTB.

PMID- 7519877
TI  - A 3-Mb physical map of the chromosome region 8p21.3-p22, including a 600-kb
      region commonly deleted in human hepatocellular carcinoma, colorectal cancer, and
      non-small cell lung cancer.
AB  - To isolate a putative tumor suppressor gene(s), we have constructed a physical
      map and a detailed deletion map of chromosome region 8p21.3-p22, where loss of
      heterozygosity (LOH) has been frequently seen in human hepatocellular carcinomas
      (HCC), colorectal cancers (CRC), and non-small cell lung cancers (NSCLC). The
      smallest commonly deleted region at 8p21.3-p22 in HCC and CRC was between the
      loci defined by C18-245 and C18-2644; in NSCLC, a region between C18-1051 and C18
      2644 was commonly deleted. A contiguous physical map of 12 cosmid markers in the
      8p21.3-p22 region was constructed by means of multi-color fluorescence in situ
      hybridization (FISH) and pulsed-field gel electrophoresis (PFGE). On the basis of
      this physical map, which spans roughly 3.1 Mb, the estimated sizes of the
      commonly deleted regions were at most 1.2 Mb in HCC and CRC and 0.6 Mb in NSCLC.
      As four of the 12 physically ordered markers are located within the 0.6 Mb region
      commonly deleted in all three tumor types, nearly one fourth to one fifth of the
      target region has already been covered with cosmid inserts.

PMID- 7519879
TI  - The effect of risperidone and ritanserin on human IgG and IgM synthesis in vitro.
AB  - We tested risperidone and ritanserin, serotonin-S2 receptor antagonists, for
      their effects on in vitro polyclonal IgG and IgM synthesis by human peripheral
      blood mononuclear cells (PBMC) stimulated with pokeweed mitogen (PWM). On the
      basis of the previously reported effect on immune function in vivo risperidone in
      this study was tested in three different groups of PBMC: healthy donors as well
      as schizophrenic patients before risperidone treatment and schizophrenic patients
      after the treatment with risperidone. IgG and IgM production after 7 days of
      culture was measured by ELISA. Risperidone decreased IgG synthesis (p < 0.05) in
      PBMC of healthy subjects only at the highest concentration (10(-6) M) and IgG
      synthesis enhanced by 5-HT was antagonized by risperidone. This effect, however,
      was not statistically significant. Neither risperidone nor ritanserin, in the
      concentration range 10(-8)-10(-6) M, affected IgM synthesis in this group.
      Risperidone did not affect the production of IgG and IgM by PBMC of schizophrenic
      subjects in PWM-stimulated cultures both before and after risperidone therapy.
      The spontaneous production of IgG in PBMC of schizophrenic subjects before
      therapy was decreased (p < 0.05) at concentrations 10(-6)-10(-7) M of
      risperidone. We conclude that risperidone and ritanserin did not increase
      polyclonal IgG and IgM synthesis in vitro in contrast to neuroleptics currently
      used in clinical practice.

PMID- 7519878
TI  - Localisation of the breast-ovarian cancer susceptibility gene (BRCA1) on 17q12-21
      to an interval of < or = 1 cM.
AB  - A breast-ovarian cancer susceptibility gene, BRCA1, which is responsible for
      disease in approximately 45% of breast cancer families and most families that
      contain breast and ovarian cancer, has been assigned by genetic linkage to 17q12
      21. Here, we report the analysis of three marker-disease recombinants in families
      that contain breast and ovarian cancer, two of which strongly suggest a location
      for BRCA1 telomeric to D17S702, a microsatellite polymorphism, and a third which
      suggests a location centromeric to EDH17B, the gene encoding estradiol-17B
      dehydrogenase. If the interpretation of these recombinants is correct, the
      results localise BRCA1 to an interval of < or = 1 cM.

PMID- 7519881
TI  - [Clinical diagnosis of Helicobacter pylori infection in adults].

PMID- 7519880
TI  - Inhibition of red cell urea flux by anion exchange inhibitors.
AB  - When they studied the chemical properties of red cell anion exchange inhibitors
      such as DIDS (4,4'-diisothiocyanate-2,2'-stilbene disulfonate), Barzilay et al.
      (1979) Membr. Biochem. 2, 227-254 also examined the benzene sulfonates. These
      molecules are structurally similar to half a DIDS molecule and are also specific
      anion exchange inhibitors with ID50 values measured in mM, rather than microM, as
      for the stilbene disulfonates. We have studied several inhibitors of the benzene
      sulfonate (BS) class and found that they also inhibit red cell urea flux by up to
      92% and stimulate water flux by up to 58%. The values of Kinhib,app for urea flux
      inhibition are the same as the ID50 values for anion flux inhibition; covalent
      DIDS completely suppresses the inhibition. These observations strongly suggest
      that the effect on urea flux is caused by BS binding at the stilbene site.
      Comparative studies on the short chain amides exclude lipid solubility and solute
      molar volume as factors that affect these BS actions. Kstim,app for water flux
      stimulation is also related to the anion exchange ID50 values; covalent DIDS
      suppresses the water flux stimulation. These observations on urea and water
      fluxes are consistent with a common driver, located at the stilbene site, which
      is responsible for the BS actions on urea, water and anion fluxes. The subsequent
      steps are independent with separate effectors to modulate each of the individual
      fluxes. These effectors are presumably located in different regions of the
      protein or proteins and carry out their separate processes by allosteric means.

PMID- 7519882
TI  - [Clinical diagnosis of Helicobacter pylori infection in the child].

PMID- 7519884
TI  - Correction of cAMP-stimulated fluid secretion in cystic fibrosis airway
      epithelia: efficiency of adenovirus-mediated gene transfer in vitro.
AB  - Adenovirus vectors are a promising vehicle to deliver cystic fibrosis
      transmembrane conductance regulator (CFTR) cDNA to airway epithelia. However, the
      value of adenovirus vectors will depend on the efficiency with which the vector
      can correct the defective fluid transport that is though to underlie the
      pathogenesis of the disease. To address the efficiency of gene transfer, we
      applied adenovirus vectors expressing CFTR (Ad2/CFTR-1) or beta-galactosidase to
      the mucosal surface of primary cultures of airway epithelial cells grown as
      polarized epithelial monolayers on permeable filter supports. These conditions
      provide a model that reproduces the physiology of the airways in vivo. We found
      that after adding 1 moi Ad2/CFTR-1 to the mucosal surface, cAMP agonists
      stimulated fluid secretion that was within the range observed in epithelia from
      normal subjects. When we measured electrolyte transport, we found that as little
      as 0.1 moi partially restored cAMP-stimulated Cl- secretion, and at 10 moi Cl-
      secretion was in the normal range. A related vector encoding beta-galactosidase
      generated activity in approximately 20% of cells at an moi of 1 and 90% of cells
      at an moi of 10. These data suggest that Ad2/CFTR-1 is very efficient at
      restoring normal fluid and electrolyte transport to CF airway epithelia. Thus,
      they suggest that relatively low input doses could be used for gene transfer to
      CF airway epithelia.

PMID- 7519883
TI  - [From Campylobacter to Helicobacter].

PMID- 7519885
TI  - Gene therapy for cystic fibrosis using E1-deleted adenovirus: a phase I trial in
      the nasal cavity. The University of North Carolina at Chapel Hill.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease that reflects mutations in
      the CFTR gene. Multiple mutations in this gene have been detected that lead to a
      protein (CFTR) that is abnormally metabolized, dysfunction, or both. The full
      spectrum of the activities of the gene product have not been defined, but it is
      clear that CFTR can act as a cAMP-regulated Cl- channel. This type of defect is
      consistent with the physiologic characterization of CF epithelia, which has
      revealed abnormalities in salt and water transport. In the lung, abnormalities in
      epithelial salt and water metabolism lead to abnormal mucociliary clearance. This
      defect in clerance represents a major failure of lung defense and leads
      ultimately to infection of the lung with Staphylococcus aureus, Pseudomonas
      aeruginosa, and other bacterial organisms. The chronic inflammatory response to
      this persistent intraluminal bacterial infection leads to protease-induced
      destruction of airway walls and finally, lung failure. More than 95% of CF
      patients die of lung disease. The clinical therapy of CF lung disease is limited
      to agents designed to promote clearance of secretions from the lung and
      antibiotics to treat the chronic bacterial infection. Recent laboratory
      demonstrations that introduction of the normal CFTR cDNA into CF cells corrects
      the ion transport defects of these cells has led to the hypothesis that gene
      therapy in the lung can be an effective, novel mode of therapy for this lung
      disease. The classic gene transfer vectors, e.g., retroviruses, appear to be not
      well suited for therapy of lung disease because of the low proliferation rate of
      airway epithelia in vivo. Recently, adenoviruses, which have a natural tropism
      for airway epithelia, have been genetically modified (E1-deleted) in an attempt
      to reduce potential toxicity of this virus and provide space for the CFTR cDNA. A
      series of in vitro studies have shown that this vector is highly efficient for
      transferring CFTR into airway epithelial cells in culture and correcting the CF
      defect. Further, studies in whole animals appear to indicate that this mode of
      gene transfer is associated with a low degree of toxicity. The present study is a
      dose-effect study designed to test for the safety and efficacy of E1-deleted
      recombinant adenovirus containing the CFTR cDNA under a CMV-beta-actin promoter
      in CF nasal epithelia.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7519886
TI  - Synapses on axon collaterals of pyramidal cells are spaced at random intervals: a
      Golgi study in the mouse cerebral cortex.
AB  - In this study we investigated the arrangement of synapses on local axon
      collaterals of Golgi-stained pyramidal neurons in the mouse cerebral cortex. As
      synaptic markers we considered axonal swellings visible at high magnification
      under the light microscope. Such axonal swellings coincide with synaptic boutons,
      as has been demonstrated in a number of combined light and electron microscopic
      studies. These studies also indicated that, in most cases, one bouton corresponds
      precisely to one synapse. Golgi-impregnated axonal trees of 20 neocortical
      pyramidal neurons were drawn with a camera lucida. Axonal swellings were marked
      on the drawings. Most swellings were 'en passant'; occasionally, they were
      situated at the tip of short, spine-like processes. On axon collaterals, the
      average interval between swellings was 4.5 microns. On the axonal main stem, the
      swellings were always less densely packed than on the collaterals. Statistical
      analysis of the spatial distribution of the swellings did not reveal any special
      patterns. Instead, the arrangement of swellings on individual collaterals follows
      a Poisson distribution. Moreover, the same holds to a large extent for the entire
      collection of pyramidal cell collaterals. This suggests that a single Poisson
      process, characterized by only one rate parameter (number of synapses per unit
      length), describes most of the spatial distribution of synapses along pyramidal
      cell collaterals. These findings do not speak in favour of a pronounced target
      specificity of pyramidal neurons at the synaptic level. Instead, our results
      support a probabilistic model of cortical connectivity.

PMID- 7519887
TI  - Pancreatitis induced by pentavalent antimonial agents during treatment of
      leishmaniasis.
AB  - Pentavalent antimony (Sbv), formulated as sodium stibogluconate or meglumine
      antimoniate, is the standard treatment for the leishmaniases. In 16 of 17
      consecutive, prospectively observed patients in Washington D.C., serum levels of
      amylase and lipase rose to abnormal values after therapy with sodium
      stibogluconate was started; 12 of 17 had symptoms of pancreatitis. Sbv therapy
      was continued to completion in 7 of 17 patients and interrupted in 10 of 17.
      Pancreatitis improved in every patient after Sbv therapy was stopped. Sbv
      treatment was resumed after brief interruptions in 6 of 10 patients. All six of
      these patients had flares of pancreatitis, but each completed therapy.
      Subsequently, we measured amylase and lipase levels in stored sera from 32
      patients treated in Peru with either sodium stibogluconate or meglumine
      antimoniate for mucosal leishmaniasis. In all 32 Peruvian patients, serum amylase
      and lipase rose to abnormal levels during Sbv therapy; 11 of 32 had symptoms of
      pancreatitis. Standard Sbv regimens induce pancreatitis in almost all patients,
      but continued therapy is often tolerated; pancreatitis subsides when therapy is
      stopped, and rechallenge may be tolerated after a brief halt in treatment.

PMID- 7519889
TI  - Clinical applications of a direct assay of free protein S antigen using
      monoclonal antibodies. A study of 59 cases.
AB  - A new one-step ELISA using two monoclonal antibodies specific for distinct
      epitopes of the free form of protein S (ELISA-m) has been developed for the
      direct measurement of free protein S in untreated plasma. This assay has been
      compared with the classic method using polyclonal antibodies to protein S (ELISA
      p). The latter method has the drawback of requiring PEG precipitation of plasma
      which is time-consuming, difficult to perform with accuracy and therefore poorly
      reproducible in most laboratories. Results of both ELISAs were compared with
      those of a functional assay. In 30 normal subjects, there was an excellent
      correlation between ELISA-m and ELISA-p (r = 0.95) as well as between ELISA-m and
      the functional assay (r = 0.96). In twelve patients with a congenital deficiency,
      the levels of free protein S antigen were similarly decreased with ELISA-m and
      ELISA-p and in good agreement with those of protein S activity. In 20 patients
      with miscellaneous inflammatory diseases, the levels of free proteins S were
      normal with good correlation between both ELISAs and PS activity, despite high
      levels of C4bBP-protein S complexes. As expected, in 15 dicoumarol-treated
      patients, there was a significant and parallel decrease of free protein S antigen
      with both ELISAs, with even lower levels of protein S activity. In 14 patients
      with liver cirrhosis, the mean values for free protein S antigen were normal
      using both assays, but with wide extreme values, whereas protein S activity was
      significantly lower.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519888
TI  - New direct assay of free protein S antigen using two distinct monoclonal
      antibodies specific for the free form.
AB  - Monoclonal antibodies (mAbs) specific for free protein S and devoid of reactivity
      with protein S-C4b-BP complexes, have been produced. A one-step sandwich-type
      enzyme-linked immunoassay (ELISA) has been developed with two mAbs reacting with
      distinct epitopes of free protein S. F(ab')2 fragments from mAb 15C4 were coated
      on microplates and mAb 34G2 conjugated with horseradish peroxidase (HRP) was
      added immediately before diluted plasma. The presence of calcium in the sample
      diluent prevented dissociation of complexes during the assay. This assay was
      specific as demonstrated by good recovery of purified protein S added to plasma
      and the lack of influence of C4B-BP-protein S complexes. Thus, addition of
      increasing amounts of purified C4B-BP to human citrated plasma induced a dose
      dependent decrease of free protein S. The assay was sensitive, allowing
      measurement of 5-500 ng/ml of free protein S, with a detection threshold of 2
      ng/ml. It was also reproducible with inter-assay and intra-assay variation
      coefficients of 2.5-5.1% and 3.1-5.0%, respectively. Thus, this new ELISA of free
      protein S antigen in plasma has the advantages of being fast, accurate and
      reproducible. It appears to be extremely useful for routine studies as no
      preliminary treatment of plasma is required.

PMID- 7519890
TI  - The detection of D-dimer in plasma by enzyme immunoassay: improved discrimination
      is obtained with a more specific signal antibody.
AB  - Most commercial D-dimer enzyme immunoassays employ two antibodies, a fibrin
      specific capture monoclonal and a less specific antibody cross-reacting with
      epitopes present on fibrinogen. Two different ELISA systems were compared to test
      whether this cross-reaction can lead to overestimation of the true levels of
      cross-linked fibrin derivatives. Both assays used the same D-dimer specific
      antibody for capture, DD-3B6/22, but utilized signalling antibodies which
      differed in fibrinogen reactivity. The assays gave low results for 210 normal
      samples (conventional ELISA, 39 +/- 45 ng/ml; non-fibrinogen reactive ELISA, 23
      +/- 20 ng/ml) with a high degree of elevation for 53 patients with active
      thrombosis (conventional ELISA, 901 +/- 649 ng/ml; non-fibrinogen reactive ELISA,
      1,906 +/- 1,725 ng/ml). However, a dramatic difference between results was seen
      when fibrinogenolysis was induced by treatment of 20 normal plasmas with high
      levels of t-PA and plasminogen. The D-dimer levels estimated with the
      conventional fibrinogen-reactive signal antibody rose 25-fold (normal, 36 +/- 27
      ng/ml; treated, 833 +/- 272 ng/ml), whereas no increase was obtained with the non
      fibrinogen reactive ELISA (normal, 24 +/- 21 ng/ml; treated, 27 +/- 22 ng/ml).
      These results suggest that a more accurate estimation of D-dimer levels in
      samples containing high levels of fibrinogen derivatives is achieved in assays
      incorporating non-fibrinogen reactive antibodies.

PMID- 7519891
TI  - Shedding of adhesion receptors from the surface of activated platelets.
AB  - When platelets are activated, several receptors are removed from the platelet
      surface. Cytoskeletal reorganizations can cause receptors to redistribute to
      intracellular membranes. In addition, receptors can be removed from the platelet
      surface by shedding of the receptor from the cell. Shedding can occur by at least
      two mechanisms. First, glycoprotein (GP)Ib alpha and GP V are shed from the
      membrane as a result of the proteolytic cleavage of the extracellular domain of
      these receptors from the platelet. The protease responsible for this cleavage
      appears to be a membrane-bound divalent cation-dependent protease other than
      calpain. Proteolytic cleavage does not occur until secretion is well under way
      and occurs whether platelets aggregate or not. Soluble forms of both GP Ib alpha
      and GP V are present in the plasma, where they may serve as feedback inhibitors
      limiting the development of thrombi. Future studies will be needed to identify
      the protease(s) responsible for removing the membrane receptors and to determine
      whether cleavage of the receptors from activated platelets results from
      activation of the protease(s), exposure of the protease(s), or an altered
      exposure of the protease-sensitive sites on the receptors. It will be of
      particular interest to determine whether the protease(s) that cleaves GP Ib alpha
      and GP V in platelets is the same as the protease(s) that cleaves receptors from
      the surface of other activated cells. Receptors also are shed from the surface of
      activated platelets by the generation of microvesicles from the plasma membrane.
      These microvesicles appear to contain all of the major membrane glycoproteins but
      are depleted in those that have been removed from the platelet membrane by
      proteolytic cleavage. The primary mechanism responsible for the shedding of
      microvesicles from the surface of platelets stirred with physiological agonists
      involves activation of calpain, which cleaves components of the membrane skeleton
      and dissociates it from the plasma membrane GP Ib-IX complex. Microvesicles are
      present in the circulation and increase under conditions in which platelet
      activation is known to have occurred. Because they contain functional adhesive
      receptors and procoagulant activity on their surface, they may function to
      disseminate procoagulant activity and stabilize the formation of platelet clots.

PMID- 7519893
TI  - A study of primary- and re-infection with hepatitis C virus in blood transfusion
      recipients.
AB  - A nested polymerase chain reaction was used to assess viraemia in blood
      transfusion recipients with no serological evidence of hepatitis C virus (HCV)
      infection (naive recipients) and in recipients with prior or existing HCV
      infection (infected recipients), who were transfused with HCV-positive blood. In
      10 hepatitis cases in naive recipients, defined as primary infection, nine showed
      clinical hepatitis, and one was sub-clinical; the time between transfusion and
      elevation of alanine aminotransferase (ALT) levels was 15-60 days (37.9 +/-
      13.9). All 10 naive recipients showed abnormal ALT, and 10/10 and 7/10 were
      persistently positive for anti-HCV and HCV-RNA, respectively, for more than 1
      year. Similarly, in five cases in previously infected recipients, defined as re
      infection, 4/5 showed clinical hepatitis, the time to elevation of ALT was 30-46
      days (34.8 +/- 6.4), and 5/5 and 3/5 were persistently positive for anti-HCV and
      HCV-RNA, respectively, for more than 1 year. All five infected recipients showed
      abnormal ALT. In conclusion, there was no significant difference (P = 0.05) in
      the frequency of the markers of infection resulting from primary or re-infection
      with HCV, suggesting that primary infection fails to induce a protective immune
      response.

PMID- 7519892
TI  - Autocrine and paracrine roles for growth factors in melanoma.
AB  - Distinct biologic and histopathological features characterizing each stage of
      tumor progression toward a more aggressive phenotype have been defined in the
      human melanocytic cell system. One of the most significant aspects accompanying
      melanoma progression is the acquisition of growth autonomy and the expression of
      multiple growth factors and receptors by tumor cells but not by normal
      melanocytes. Among the growth factors produced by melanoma cells, bFGF, TGF
      alpha, TGF-beta, PDGF A and B chains, MGSA, and interleukins have been
      extensively characterized. The complex signaling networks mediated by these
      melanoma-derived factors are responsible for the autocrine growth stimulation of
      melanoma cells and for paracrine actions of growth factors in the generation of a
      microenvironment favorable for tumor survival and invasion. bFGF is the best
      characterized candidate for autocrine stimulation in melanoma cells. In addition,
      bFGF and other growth factors not apparently involved in autocrine loops have
      been shown to activate neighboring stromal cells and to participate in
      angiogenesis, fibrous stroma formation, activation of proteolytic enzymes
      produced by normal cells, promotion of adhesive interactions between tumor cells
      and extracellular matrix and endothelium, and suppression of local immunity.
      Experimental models that can account for the complex interactions between normal
      and tumor cells are needed to further explore the roles of autocrine and
      paracrine actions of growth factors and their receptors in melanoma development
      and progression.

PMID- 7519894
TI  - Clinical usefulness of an assay for hepatitis C virus core in the diagnosis of
      non-A, non-B hepatitis and monitoring of the response to interferon therapy.
AB  - The clinical utility of a new JCC-2 enzyme-linked immunosorbent assay kit that
      detects and quantitates anti-hepatitis C virus (anti-HCV) core antibodies (anti
      HCc) was investigated. Serum samples were obtained from 102 patients with various
      non-A, non-B liver diseases, including 19 cases of chronic hepatitis type C who
      had been treated with interferon (IFN). The results of the anti-JCC-2 assay were
      significantly correlated with serum HCV-RNA positivity. Patients who were HCV-RNA
      positive exhibited a high rate of positivity for anti-JCC-2 (72.2% in acute
      hepatitis, > 90% in chronic liver diseases). The geometric mean of the anti-JCC-2
      titre was not significantly different among different stages of chronic liver
      disease (among CPH, CAH and LC). The anti-JCC-2 titre decreased gradually in
      cases that became HCV-RNA negative after IFN therapy. If HCV-RNA positivity
      recurred, the anti-JCC-2 titre increased, indicating that serial measurements of
      the anti-JCC-2 titre are useful for monitoring the antiviral effect of IFN
      treatment. These results suggest that quantification of anti-HCc by the anti-JCC
      2 assay is superior to the semi-quantification of circulating HCV-RNA provided by
      monitoring of IFN therapy. Monitoring of HCV-RNA status using reverse
      transcription-nested polymerase chain reaction (RT-nested PCR) is possible, but
      it is technically demanding and too expensive for routine clinical use.

PMID- 7519896
TI  - Incidence of hepatitis C virus (HCV) antibodies and HCV-RNA in blood donors and
      patients with liver diseases in the inshore area of the Yangtze River.
AB  - The Nantong area is a high risk region for primary hepatocellular carcinoma (PHC)
      in the inshore area of the Yangtze River. However, no detailed data are available
      about hepatitis C virus (HCV) infection in this area. We examined the incidences
      of anti-HCV and HCV-RNA in blood donors with hepatitis B surface antigen (HBsAg)-
      and hepatitis B core antibody (HBcAb)-negative and patients with chronic liver
      diseases in the Nantong area at Nantong Medical College, Jiangsu Province, the
      People's Republic of China. The incidences of HBV markers (HBsAg and/or HBcAb),
      anti-HCV (C100-3), second generation anti-HCV, HCV-RNA and any marker of HCV in
      the Nantong area were found to be: 0.0, 0.7, 0.4, 0.2 and 0.7% in donor bloods;
      16.9, 0.0, 3.4, 15.7 and 16.9% in patients with acute hepatitis; 82.8, 2.7, 4.8,
      7.5 and 10.2% in those with chronic hepatitis; 86.4, 4.5, 9.1, 4.5 and 11.4% in
      those with liver cirrhosis; 87.5, 6.3, 0.0, 0.0 and 6.3% in those with PHC; and
      21.8, 1.3, 1.3, 0.0 and 1.3% in patients without liver diseases, respectively.
      Although the Nantong area is a high risk region for PHC, these data suggest that
      HCV infection is not an important aetiological factor for PHC in this area.

PMID- 7519895
TI  - A dynamic study of viraemia in chronic hepatitis C infection.
AB  - The dynamics of alanine aminotransferase (ALT), anti-hepatitis C virus and
      hepatitis C virus (HCV) RNA in six cases with chronic HCV infection were studied
      for 3-7 years. Two of the six cases showed continued elevation of ALT, and three
      showed intermittent elevation. All cases were persistently positive for anti-HCV
      after initial seroconversion. Five of the six cases were persistently positive
      for HCV RNA detected by nested polymerase chain reaction, and one was positive
      intermittently. Thus hepatitis C virus replicates continually in a majority of
      patients with chronic hepatitis C, although some cases may show intermittent
      replication, and replication of hepatitis C virus does not always correlate with
      elevated ALT.

PMID- 7519897
TI  - Serum alpha 2-macroglobulin-trypsin complex and early recognition of severe acute
      pancreatitis after endoscopic retrograde pancreatography.
AB  - Serum alpha 2-macroglobulin-trypsin complex (alpha 2M-T) was measured to
      differentiate the elevation of serum pancreatic enzymes caused by severe acute
      pancreatitis from simple elevation after endoscopic retrograde pancreatography
      (ERP). A patient with severe acute pancreatitis demonstrated marked elevation of
      serum alpha 2M-T. In patients without severe acute pancreatitis, serum alpha 2M-T
      did not rise in spite of elevated serum pancreatic enzymes. In conclusion,
      abdominal pain with elevated serum alpha 2M-T can be an early diagnostic clue to
      severe acute pancreatitis after ERP.

PMID- 7519900
TI  - [Changes in hemodynamic parameters and temperature regimen in the system mother
      placenta-fetus as affected by various drugs].
AB  - In the chronic experiments at the end of pregnancy the effects of the infusion to
      mother of some drugs (trental, reopolyglucin and their combination) on the female
      of a rabbit and its fetuses normally developed and growth retarded were studied.
      It was found that changes in the intensity of maternal-placental blood flow,
      induced by the infusion of drugs to mother lead to the changes of gradient
      between temperature of fetus and mother, which reflect intensity of feto
      placental blood flow and consequently the intensity of fetal heat loss. The
      possible unfavourable influence of these drugs on fetus temperature regimen and
      consequently on its metabolic processes under the treatment of placental
      insufficient and growth retardation have been taken into consideration.

PMID- 7519899
TI  - [The nitinol stent as a palliative measure in inoperable carcinoma of the
      esophagus and cardia. Possibilities and limitations of the procedure].
AB  - Nitinol stents were used in ten patients as palliative treatment for carcinoma of
      the esophagus and the cardia. Following insertion of the stent the severity of
      dysphagia decreased on average from 3.2 to 1.5 (on a scale from 0-4).
      Difficulties with stent opening and passage through the gut were found
      particularly in the region of metal sutures at esophago-jejunal anastomoses. One
      stent, which had been obstructed by mucosal folds, had to be removed and
      replaced. One stent which had been incorrectly placed was extended by introducing
      a second stent by a coaxial technique. During the period of observation, six
      patients died after an average of 4.6 months. The palliative effect of the stent
      lasted on average for eleven weeks. In two patients the tumour grew beyond the
      stent and in three there was tumour growth into the stent.

PMID- 7519901
TI  - [Solcoseryl: Ulcerostatic effect and possible mechanisms].
AB  - It is shown that the level of DNA, RNA, collagen, non-collagen proteins, hexoses
      and glycosaminoglycans is changed when making the experimental gastric ulcer in
      rats. Solcoseryl stabilises the level of DNA, RNA and collagen, stimulating the
      reparation processes in ulcer.

PMID- 7519898
TI  - Use of the receptor globulin technology to search for ligands for
      glycosylphosphatidylinositol-linked cell surface antigens.
AB  - The ability of monoclonal antibodies to several proteins coupled to the membrane
      by a glycosylphosphatidylinositol anchor to induce T cell activation has
      suggested that these proteins interact with cellular ligands or counter
      receptors. The murine Ly-6 antigens and the closely-related human CD59 antigen
      play important roles in T cell activation, B cell activation and cell-cell
      interactions. Receptor globulins containing the external domains of Ly-6A.2 or
      CD59 coupled to hinge-CH2-CH3 regions of human IgG1 were generated. When these
      fusion proteins were used to stain lymphoid tissues, they selectively reacted
      with B lymphocytes. On mouse B cells, their target antigen is membrane IgM, while
      their target on human B cells has not been fully defined. These results suggest
      that Ly-6/CD59-IgM may be a receptor-counter-receptor pair and may play a role in
      T-B cell interactions.

PMID- 7519902
TI  - [Mott cells in the lymph].
AB  - For the first time Mott cells have been found in the lymph. The lymph was
      obtained with the help of glass micropipettes from cisterna chyli of rabbits. The
      Mott cells in Romanovsky-Giemsa-stained lymph smears were examined in a light
      microscope. The Mott cells of the lymph preserve their unique morphological
      characteristics. They usually have a rounded form. The cytoplasm of Mott cells is
      divided into many liquid spheres which dominate the cell interior and are grouped
      in several rows round a blue-stained nucleus. The number of the Mott cells in the
      lymph doubles in atherosclerosis in comparison with the norm. It is related with
      the reaction of the immune system to atherosclerosis.

PMID- 7519903
TI  - Application of cationic probes for the ultrastructural localization of
      proteoglycans in basement membranes.
AB  - The application of cationic probes for the ultrastructural detection of
      proteoglycans in basement membranes is reviewed. Proteoglycans are highly
      negatively charged macromolecules due to their glycosaminoglycan side chains. The
      interaction of cationic probes with proteoglycans is of an electrostatic nature.
      Methods are discussed to increase the specificity of probes for proteoglycans.
      The use of phthalocyanin-like dyes such as Cuprolinic blue, according to the
      critical electrolyte concentration method, results in a selective staining of
      proteoglycans. Enzymatic or chemical digestions, however, should be done to
      validate the proteoglycan nature of the dye-positive granules/filaments, and to
      establish the class of proteoglycan. The value of cationic probes in basement
      membrane research on development and pathology is discussed. The potential for
      deducting molecular information from the ultrastructural appearance of stained
      proteoglycans is indicated.

PMID- 7519906
TI  - [Transmission electron microscopy in the structural study of superparamagnetic
      contrast agents for MRI].
AB  - Iron oxide nanoparticles with different crystal sizes and uniform dextran coating
      were synthesized and analyzed by T.E.M.. The iron oxide core dimension and
      homogeneity of the preparation were correlated to magnetic properties. The
      increasing Fe/Dextran ratio used for the synthesis was well correlated with the
      mean diameter and the magnetic susceptibility. The comparison of the crystal size
      with the particle size determined by nanosizer in solution suggest that particles
      consist in nanoaggregates of many crystal subunits.

PMID- 7519907
TI  - Primary culture of smooth muscle cells from benign prostatic hyperplasia.
AB  - Primary cultures of smooth muscle cells (SMCs) were derived from the human
      prostate obtained from four patients with symptomatic benign prostatic
      hyperplasia (BPH) undergoing open prostatectomy, using collagenase digestion and
      preferential adhesion techniques. SMCs attached to the plastic substrate by 6 to
      10 h, proliferated by 2 to 3 days, and reached confluency by 10 to 14 days with a
      "hill-and-vallery" pattern. Immunocytochemical staining of cultured SMCs using
      anti human muscle-specific actin monoclonal antibody (HHF35), confirmed that more
      than 90% primary cultured cells were positive for HHF-35. Transmission electron
      microscopy of SMCs revealed dense myofibrils (6-8 nm width) showing focal
      density, and was compatible to smooth muscle cells. This primary culture will be
      utilized to provide a useful model to investigate the character of smooth muscle
      cells and their role in the development of BPH.

PMID- 7519905
TI  - The extracellular matrix ligands fibronectin and tenascin collaborate in
      regulating collagenase gene expression in fibroblasts.
AB  - Tenascin (TN) is a large oligomeric glycoprotein that is present transiently in
      the extracellular matrix (ECM) of cells and is involved in morphogenetic
      movements, tissue patterning, and tissue repair. It has multiple domains, both
      adhesive and anti-adhesive, that interact with cells and with fibronectin (FN)
      and other ECM macromolecules. We have studied the consequences of the interaction
      of TN with a FN matrix on gene expression in rabbit synovial fibroblasts.
      Fibroblasts plated on a mixed substrate of FN and TN, but not on FN alone,
      upregulated synthesis of four genes: collagenase, stromelysin, the 92-kDa
      gelatinase, and c-fos. Although the fibroblasts spread well on both FN and FN/TN
      substrates, nuclear c-Fos increased within 1 h only in cells that were plated on
      FN/TN. TN did not induce the expression of collagenase in cells plated on
      substrates of type I collagen or vitronectin (VN). Moreover, soluble TN added to
      cells adhering to a FN substrate or to serum proteins had no effect, suggesting
      that TN has an effect only in the context of mixed substrates of FN and TN.
      Collagenase increased within 4 h of plating on a FN/TN substrate and exhibited
      kinetics similar to those for induction of collagenase gene expression by
      signaling through the integrin FN receptor. Arg-Gly-Asp peptide ligands that
      recognize either the FN receptor or the VN receptor and function-perturbing anti
      integrin monoclonal antibodies diminished the interaction of fibroblasts with a
      mixed substrate of FN, TN, and VN, but had no effect on the adhesion of
      fibroblasts to a substrate of FN and VN, suggesting that both receptors recognize
      the complex. Anti-TN68, an antibody that recognizes an epitope in the carboxyl
      terminal type III repeats involved in the interaction of TN with both FN and
      cells, blocked the inductive effect of the FN/TN substrate, whereas anti-TNM1, an
      antibody that recognizes an epitope in the amino-terminal anti-adhesive region of
      epidermal growth factor-like repeats, had no effect. These data suggest that
      transient alteration of the composition of ECM by addition of proteins like TN
      may regulate the expression of genes involved in cell migration, tissue
      remodeling, and tissue invasion, in regions of tissue undergoing phenotypic
      changes.

PMID- 7519908
TI  - Contractile responses of longitudinal muscle strip to 5-HT and influences of
      divalent cations in the guinea-pig isolated colon.
AB  - The contractile effects of 5-hydroxytryptamine (5-HT) and influences of several
      kinds of divalent cations were investigated on longitudinal muscle strips of the
      guinea-pig isolated distal colon. 5-HT (10 nM-10 microM) produced phasic
      contractions which were partially inhibited by atropine (1 microM) and markedly
      inhibited by tetrodotoxin (1 microM), indicating that 5-HT acts mainly on the
      myenteric plexus and releases transmitters to cause contraction of the
      longitudinal muscle. The contractile response to 5-HT (3 microM) was almost
      completely inhibited by spantide (10 microM), a substance P antagonist, in the
      presence of atropine (1 microM), while spantide alone did not block 5-HT-induced
      contraction. Of several divalent cations including Cd2+, Co2+, Mg2+, Mn2+, Ni2+,
      Sr2+ and Zn2+, Cd2+ ions (10 mu-100 microM), which block L- and N-type Ca2+
      channels, were most effective inhibitor of the 5-HT-induced contractions. While
      Sr2+ and Co2+ at a concentration of 100 microM did not have a significant effect.
      The order effectiveness of inhibition was Cd2+ >> Mn2+ > Mg2+ = Ni2+ = Zn2+. Bay
      K 8644 (1 microM), a L-type Ca2+ channel activator, did not influence the
      contractile response of the longitudinal muscle strip to 5-HT (3 microM). The
      present results suggest that 5-HT may mainly act on N-type Ca2+ channels in the
      myenteric neurones and cause the release of at least acetylcholine and substance
      P to induce contractions of the longitudinal muscle in the guinea-pig distal
      colon.

PMID- 7519904
TI  - Cell-type specific adhesive interactions of skeletal myoblasts with
      thrombospondin-1.
AB  - Thrombospondin-1 (TSP-1) is an extracellular matrix glycoprotein that may play
      important roles in the morphogenesis and repair of skeletal muscle. To begin to
      explore the role of thrombospondin-1 in this tissue, we have examined the
      interactions of three rodent skeletal muscle cell lines, C2C12, G8, and H9c2,
      with platelet TSP-1. The cells secrete thrombospondin and incorporate it into the
      cell layer in a distribution distinct from that of fibronectin. Myoblasts attach
      and spread on fibronectin- or thrombospondin-coated substrates with similar time
      and concentration dependencies. Whereas cells adherent on fibronectin organize
      actin stress fibers, cells adherent on TSP-1 display prominent membrane ruffles
      and lamellae that contain radial actin microspikes. Attachment to thrombospondin
      1 or the 140-kDa tryptic fragment is mediated by interactions with the type 1
      repeats and the carboxy-terminal globular domain. Attachment is not inhibited by
      heparin, GRGDSP peptide, or VTCG peptide but is inhibited by chondroitin sulphate
      A. Integrins of the beta 1 or alpha V subgroups do not appear to be involved in
      myoblast attachment to TSP-1; instead, this process depends in part on cell
      surface chondroitin sulphate proteoglycans. Whereas the central 70-kDa
      chymotryptic fragment of TSP-1 does not support myoblast attachment, the carboxy
      terminal domain of TSP-1 expressed as a fusion protein in the bacterial
      expression vector, pGEX, supported myoblast attachment to 30% the level of intact
      TSP-1. Thrombospondin-4 (TSP-4) is also present in skeletal muscle and a fusion
      protein containing the carboxy-terminal domain of TSP-4 also supported myoblast
      adhesion, although this protein was less active on a molar basis than the TSP-1
      fusion protein. Thus, the carboxyterminal domain of TSP-1 appears to contain a
      primary attachment site for myoblasts, and this activity is present in a second
      member of the thrombospondin family.

PMID- 7519909
TI  - The differences in significance of alpha 2,3Gal-linked and alpha 2,6GalNAc-linked
      sialic acid residues in blood group M- and N-related epitopes recognized by
      various monoclonal antibodies.
AB  - The blood group M and N determinants of glycophorin A (GPA) contain O-linked
      oligosaccharide chains with alpha 2,3Gal-linked and alpha 2,6GalNAc-linked sialic
      acid residues which are required for the activity of most epitopes recognized by
      various anti-M and anti-N antibodies. In order to check whether these two types
      of sialic acid residues differ in their contribution to antigenic properties, the
      GPA-M and GPA-N preparations with monosialylated oligosaccharide chains were
      obtained and tested for binding of anti-M and anti-N monoclonal antibodies
      (MAbs). The GPAs with sialic acid residues linked to Gal (GPA2,3) were obtained
      by selective resialylation of asialoGPAs with alpha 2,3-sialyl-transferase. These
      preparations were tested by inhibition of binding of MAbs to enzyme-linked
      immunosorbent assay (ELISA) plates coated with the respective untreated target
      antigens. The GPAs with sialic acid residues linked to GalNAc (GPA2,6) were
      generated by treating GPAs adsorbed on ELISA plates with Newcastle disease virus
      (NDV) isolate (expressing sialidase specific for alpha 2,3Gal linkage), which was
      followed by testing the binding of MAbs to NDV-treated antigens. Different
      patterns of activity were obtained among 14 MAbs specific for sialic acid
      dependent epitopes (eight anti-M and six anti-N). The results indicated that at
      least half of the MAbs showed distinct requirements for the presence of only one
      of two kinds of sialic acid residues (Gal or GalNAc linked) in the epitope. Only
      four MAbs (two anti-M and two anti-N) did not react with any of the
      'monosialylated' forms of GPA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519910
TI  - Human protein C inhibits selectin-mediated cell adhesion: role of unique
      fucosylated oligosaccharide.
AB  - The human anticoagulant factor, Protein C, is a plasma glycoprotein that has
      reported anti-ischaemic and anti-inflammatory properties. To explore potential
      mechanisms for these reported activities, we examined the effect of Protein C on
      the process of cell adhesion to vascular endothelial cells, which plays a
      critical role during inflammatory responses. We show that both human plasma
      derived and human cell-produced recombinant Protein C inhibit E-selectin-mediated
      cell adhesion. This effect was not mediated through the serine protease activity
      of Protein C, but through its carbohydrates. Using oligosaccharides isolated from
      human cell-produced Protein C, we have defined a polylactosamine structural
      determinant that inhibits adhesion. This uncharged determinant appears to be a
      more potent ligand for E-selectin than the sialylated Lewis X antigen. Our data
      suggest a potential mechanism for the reported anti-inflammatory effects of
      Protein C and describe a new ligand for selectin-mediated adhesion.

PMID- 7519911
TI  - Does the extent of lymph node dissection affect the postoperative survival of
      patients with gastric cancer and disseminating peritoneal metastasis?
AB  - For patients with gastric cancer and either P1 or P2 peritoneal metastasis, no
      definite consistent policy with respect to the extent of lymph node dissection
      has yet been established. In palliatively gastrectomized patients, we analyzed
      the relationship between the extent of lymphadenectomy and postoperative
      survival. In patients with P1, an R2 or R3 lymphadenectomy was associated with a
      significantly improved postoperative survival as compared to an R1 dissection,
      while this, however, was not the case in patients with P2. As this study was not
      intended to be a prospective randomized study, a definite conclusion should be
      avoided. However, our findings suggest that in patients with P1, surgery should
      not be confined to a resection of the primary lesion, but should also include an
      R2 or R3 lymphadenectomy.

PMID- 7519913
TI  - Review of antithyroid drug use during pregnancy and report of a case of aplasia
      cutis.
AB  - Thioamide therapy has improved the outcome of pregnancies complicated by maternal
      hyperthyroidism, without long-term effects on cognitive and somatic development.
      However, there remain questions concerning whether these drugs, especially
      methimazole (MMI), may be associated with aplasia cutis congenita (ACC) and how
      best to avoid impairment of fetal thyroid function during their use. We report an
      example of ACC and review the relevant literature. We conclude that there is
      insufficient evidence either to establish or eliminate a direct causal
      relationship between ACC and MMI use. Since propylthiouracil is an equally
      effective antithyroid agent and has not been associated with ACC, it is the
      preferred thioamide for hyperthyroidism during pregnancy. Our review also
      indicates that impairment of neonatal thyroid function may be minimized by using
      a thioamide dose that is just sufficient to maintain the maternal serum free
      thyroxine concentration in the high normal or slightly thyrotoxic range.

PMID- 7519912
TI  - Metastases from gastric adenocarcinoma presenting as multiple colonic polyps:
      report of a case.
AB  - A 53-year-old woman presented with symptoms of weight loss, diarrhea, and melena.
      A barium enema with endoscopy revealed multiple colonic polyps which were shown
      histologically to be metastatic deposits of poorly differentiated adenocarcinoma.
      The primary tumor, a poorly differentiated gastric adenocarcinoma, had been
      resected 11 years earlier. This appears to be only the second published report of
      polypoid colonic metastases from gastric adenocarcinoma.

PMID- 7519914
TI  - The expression of adhesion molecules in thyroid glands from patients with Graves'
      disease.
AB  - We studied the potential role of adhesion molecules in the pathogenesis of
      Graves' disease. Thyroid specimens of Graves' thyroid glands and control thyroid
      glands were stained with monoclonal antibodies against adhesion molecules by an
      immunohistologic method. Thyroid tissues obtained from patients with Graves'
      disease had an enhanced expression of intercellular adhesion molecule-1 (ICAM-1)
      on capillary endothelial cells around the thyroid follicles and on postcapillary
      endothelial cells in lesions with aggregates of mononuclear cells. Positive
      staining for ICAM-1, lymphocyte function-associated antigen-1 (LFA-1), and very
      late antigen-4 (VLA-4) was found on the infiltrating mononuclear cells. The
      postcapillary vascular endothelial cells expressed increased endothelial
      leukocyte adhesion molecule-1 (ELAM-1), but not vascular cell adhesion molecule-1
      (VCAM-1). VCAM-1 and ELAM-1 were detected on the dendritic-like cells in the
      germinal centers of lymphoid follicle-like areas. No significant expression of
      these adhesion molecules was detected on normal thyroid glands. These results
      suggest that the LFA-1/ICAM-1 and ELAM-1 pathways may be responsible for the
      migration of mononuclear cells into the thyroid glands of patients with Graves'
      disease, and that the VLA-4/VCAM-1 pathway plays a critical role in the cellular
      interactions that lead to the formation of B-memory cells and the excess
      production of antibodies.

PMID- 7519915
TI  - Proliferative responses of peripheral blood mononuclear cells from patients with
      Graves' disease to synthetic peptides epitopes of human thyrotropin receptor.
AB  - In Graves' disease thyrotropin receptor (TSH-R) autoantibodies cause
      hyperthyroidism. Production of TSH-R autoantibodies must be controlled by
      specific T cells. In this study we investigated T cell responses to 33 peptides
      corresponding to the sequence of the extracellular domain of human TSH-R.
      Peripheral blood mononuclear cells (PBMC) from 12 patients with Graves' disease
      and 9 healthy subjects were cultured with peptides for 3 days. The proliferative
      responses of PBMC were analyzed by measurement of [3H]thymidine incorporation. A
      stimulation index (SI; mean cpm in the presence of peptide/mean cpm in culture
      medium alone) of more than 3 was considered a positive response. When PBMC were
      stimulated with a pool containing all synthesized peptides, the mean SI of
      patients was significantly higher than that of controls (4.50 +/- 3.95 vs. 1.44
      +/- 0.60; p < 0.05). When PBMC were cultured with individual peptides, PBMC from
      patients responded predominantly to two peptides, corresponding to sequence
      segments 152-157 (5 patients) and 207-222 (4 patients). No PBMC from controls
      responded to these two peptides. There was no clear correlation between the HLA
      DR or HLA-DQ genotype and the stimulatory sequence segments. These results
      suggest that (a) TSH-R-specific T cells are present in peripheral blood of
      patients with Graves' disease, and (b) sequence segments 152-157 and 207-222 may
      be T cell epitopes of the human TSH-R in Graves' disease.

PMID- 7519916
TI  - Basic fibroblast growth factor (basic FGF) in isolated ovine thyroid follicles:
      thyrotropin stimulation and effects of basic FGF on DNA synthesis, iodine uptake
      and organification, and the release of insulin-like growth factors (IGFs) and IGF
      binding proteins.
AB  - We examined the effects of thyroid-stimulating hormone (TSH) on basic fibroblast
      growth factor (basic FGF) expression in isolated ovine thyroid follicles in
      vitro, and the effects of exogenous basic FGF on thyroid growth and function, to
      elucidate the significance of increased basic FGF expression during TSH-induced
      rat thyroid hyperplasia in vivo. Primary cultures of ovine thyroid follicles were
      maintained in serum-free Ham's modified F-12M medium containing transferrin,
      somatostatin, and glycyl-histidyl-lysine (designated 3H) with or without basic
      FGF alone, or in combination with TSH (100 microU/mL) and cortisol (10 nM).
      Following 48 h incubation, cells were harvested and total RNA prepared for the
      detection of basic FGF mRNA using Northern blot analysis and ribonuclease
      protection assay. Basic FGF in the cytoplasm and extracellular matrix fractions
      was quantified by radioimmunoassay. Basic FGF mRNA transcripts of 3.7, 3.0, and
      2.2 kb, respectively, were found in thyroid follicles cultured in 3H medium, and
      the abundance of each increased between 2- and 3-fold following incubation with
      10-50 microU/mL TSH, although higher concentrations of TSH were less effective.
      Similar results were seen using a more sensitive ribonuclease protection assay.
      Cells cultured in control, 3H medium contained 2.4 +/- 0.5 fmol immunoreactive
      basic FGF/micrograms cell DNA within the cytoplasm and 21.1 +/- 1.5
      fmol/micrograms DNA within the extracellular matrix (mean +/- SD, n = 6). A
      significant increase (p < 0.05) in basic FGF content was seen in both cell
      compartments following incubation with 50 or 100 microU/mL TSH, while 250
      microU/mL was less effective.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519918
TI  - [The role of cellular adhesiveness in the development of liver pathology].
AB  - The paper gives a review of the data available in the literature and an analysis
      of the authors' own data of the ultrastructural studies of the intercellular
      contacts of hepatocytes and epitheliocytes in some pathological states. It also
      shows an important role of the site of an element compound wherein the major
      molecular mechanisms of tissue homeostatic regulation display and discusses the
      contribution of macromolecular adhesive factors such as effector molecules
      capable of suppressing the development of a pathological process.

PMID- 7519917
TI  - [Clinical and prognostic significance of cellular immunity factors in patients
      with chronic liver diseases].
AB  - The paper presents the results of comprehensive studies of quantitative and
      functional parameters of cellular immunity in 283 patients with chronic liver
      diseases, using various rosette tests and monoclonal antibody phenotyping of
      immunocompetent cells. The pattern of changes in blood immunocompetent cells and
      immunoglobulins allows prediction of the natural history of chronic active
      hepatitis and hepatic cirrhosis of viral and alcoholic origin. The data on
      autorosette-forming and hepatic-specific lipoprotein-sensitive rosette-forming
      cells were found to be the most informative. As compared to health, there were
      substantial changes in the subpopulation composition of immunocompetent cells and
      immunoglobulins in hepatic cirrhosis. The changes in immunoregulatory
      theophylline-resistant (OKT4+, OKT8+, T mu and T gamma) and theophylline
      sensitive E-rosetting, as well as effector (ICO11+ and ICOHM1+) cells were the
      leading immunopathogenetic link of hepatic cirrhosis. In the latter, the
      subpopulation composition of immunocompetent cells depended on the activity of a
      pathological process, the state of compensation, as well as the levels of HBsAg
      and blood anti-delta-antibodies. The subpopulation analysis of immunocompetent
      cells enabled the author to outline the specific features of the immune status of
      etiological types, as well as predictive types of chronic active hepatitis and
      hepatic cirrhosis, which may serve as evidence for goal-oriented immunomodulating
      therapy.

PMID- 7519919
TI  - [Enzymologic factors in the development of ulcerative process in gastroduodenal
      mucosa].
AB  - The contribution of gastric proteolytic enzymes to formation of an ulcerated
      defect in the mucosa of the stomach and duodenum was studied in the experimental
      and clinical settings. There is no evidence for involvement of gastric secretory
      proteinases (pepsins) in ulceration in early periods. The secretory enzymes are
      likely to participate in maintaining the existing ulcers, preventing their
      healing. In patients with ulcerative disease and in animals with experimental
      ulcers, gastric juice is more aggressive against the mucosa than that of healthy
      human beings and animals. A possible role of carbohydrate components of gastric
      juice in the regulation of the "aggression" of gastric enzymes, as well as that
      of lysosomal enzymes in ulceration, namely the forming role of the latter during
      early ulceration are considered in the paper.

PMID- 7519922
TI  - [Intracellular oxygen activation and molecular mechanisms of oxidative hepatic
      damage].
AB  - The paper deals with the mechanisms responsible for formation of active oxygen
      forms and with the physiological and toxic aspects of their action on the cell.
      The active oxygen forms are essential biological energy metabolites, such as
      mitochondrial respiration and microsomal oxidation. It considers the specific
      features of the systems of APA by various cells (neutrophils, lymphocytes,
      fibroblasts, endothelial cells). The results of their authors' own investigations
      provide evidence for the concept that there is an oxidative damage to hepatocytes
      in liver damage, which is associated with activation of phagocytes, conversion of
      xanthine oxidase, inhibition of superoxide dismutase and catalase activity and
      accumulation of active oxygen forms.

PMID- 7519920
TI  - [Ulcer. New approach to the problem].
AB  - The paper deals with the issues of ulcerogenesis, including the value of
      Helicobacter pylori (HP) as one of the etiological and pathogenetic factors of
      ulcer diseases. The data available in the literature and the author's own
      findings have allowed the author to study the spread of HP infection. There is a
      higher incidence of ulcer disease among endoscopists than that in therapeutists
      and inhabitants in Moscow. Light and electron microscopies have demonstrated
      abnormal changes in the gastric mucosa if there is HP infection. The paper also
      analyzes the therapeutical efficiency of antiulcer drugs and their effects on the
      degree of gastric sanitation from HP.

PMID- 7519921
TI  - [Problems of enterology].
AB  - Most diagnostic problems in enterology may be solved if X-ray studies, intestino
      fibroscopy, colonoscopy, ileoscopy, and current laboratory examinations are
      properly performed. In clinical practice the value of functional tests aimed at
      specifying the severity of abnormalities in intestinal digestion, absorption, and
      motility is underestimated. The paper shows how present-day functional tools
      (regional perfusion of the small bowel, hydrogen respiratory test, etc.) may be
      used to diagnose intestinal absorption and motility. Four mechanisms of the
      pathogenesis of diarrhea are identified. These include intestinal hypersecretion,
      elevated osmotic pressure in the intestinal cavity, intestinal hyper-exudation
      and impaired intestinal contents transit. Main principles in the treatment of
      chronic diarrhea are given in relation to the prevalence of disturbed ion and
      water transport through the intestinal wall.

PMID- 7519923
TI  - [Clinical morphology of enteropathies].
AB  - The author describes the morphological substrate and pathogenesis of the most
      common enteropathies (gluten enteropathy, collagen sprue, Whipple's disease,
      common variable immunodeficiency), discusses the potentials and limits of
      morphological methods for differential diagnosis of enteropathies, emphasizes the
      high informative value of duodenal biopsies that are as good as jejuno-biopsies.
      He considers it incompetent to use the term "chronic enteritis" which is widely
      spread in our country. The term stands for nosological diagnosis, making the
      treatment of patients worse.

PMID- 7519924
TI  - [Activity of enzymes of xenobiotics metabolism in peripheral blood lymphocytes in
      man].
AB  - The activity of NADPH-cytochrome c-reductase, benzpyrene hydroxylase, epoxy
      hydratase and glutathione-S-transferase in human peripheral blood lymphocytes was
      studied. In the presence of NADPH, native lymphocytes were unable to reduce
      cytochrome c. In order to improve the availability of substrates for enzymes,
      lymphocytes were degraded by single-stage freezing-melting. At the same time, the
      activities of NADPH-cytochrome c-reductase, epoxide hydratase, and glutathione-S
      transferase were 1.7 +/- 0.6, 49.0 +/- 18.0, and 30.0 +/- 6.0 nmol/min per mg
      protein, respectively. The lymphocytic levels of cytochrome P-450 were
      approximately 0.1-0.2 nmol per mg microsomal protein, while those of cytochrome
      b5 were nearly 0.5 nmol/mg microsomal protein in the lymphocytes.

PMID- 7519926
TI  - [Characteristics of hemodynamics in persons exposed to ionizing radiation].

PMID- 7519927
TI  - [Rheumatoid blood factors in patients with complicated spinal injury].
AB  - Enzyme immunoassay (ELISA) was used to study the levels of serum rheumatoid
      factors (RF) of classes IgM and IgG in patients with spinal injuries and
      osteochondrosis. The findings show that at the late stages of the disease, the
      patients with spinal injury show 46% seropositiveness for IgG-RF and 40% for IgM
      RF. Patients with fresh central nervous system (CNS) injuries were 12 and 14%
      seropositive, respectively. Patients with osteochondrosis exhibited 33%
      seropositiveness for IgG-RF. Determination of serum RF enables the authors to
      identify systemic body lesions at the late stages of spinal injuries as rheumatic
      disease. These data support the conclusion that RF determination is a reliable
      serological indicator of the severity of a patient's traumatic disease.

PMID- 7519925
TI  - [Preventive effect of Rhodiolae rosea in spontaneous liver carcinogenesis in a
      mice model of high-tumor strain].
AB  - Different schemes of Rhodiolae rosea usage per os for prophylaxis of mouse
      hereditary hepatomas have been studied. A long-term effect on stimulation of
      tissue integration, T-immune activity and sufficient decrease of tumour frequency
      has been shown for R. rosea usage in early ontogenesis. A short-term effect on
      tissue and immune parameters has been demonstrated for R. rosea usage in middle
      ontogenesis. High-tumour frequency (as in the control), but tumour size decrease
      (comparing to the control) has been noticed in this case. A tendency to
      synchronic alterations of tissue integration and T-immune activity has been
      established in these experiments. It can be attributed to the assumption of
      communication between tissue (local) and immune (common) defence from tumour
      growth in the organism.

PMID- 7519929
TI  - [Rationale for social and hygienic methods of rehabilitation of the population of
      the areas exposed to radioactive contamination resulting from the Chernobyl
      accident].
AB  - The factors preventing the stabilization of life in the contaminated areas
      include sociopsychic epidemic of "victim's syndrome" among the population;
      unfavourable information environment; secondary negative action of contrameasures
      (obligatory behavioral limitations, privileges, compensations, etc.). The
      rehabilitation of the population's life is based on the activization of a
      personal position and initiative of individuals, stimulation of economic activity
      in the areas.

PMID- 7519928
TI  - [Myxoma syndrome].
AB  - The paper provides the follow-up findings of patients with cardiac myxomas
      according to the presence or absence of the myxomal syndrome. It is shown that it
      is a multiorgan abnormality wherein the cardiac myxomas that are prone to
      primarily multiple growth, extraseptal and/or multifocal fixation are associated
      with the changes in the hypothalamus-pituitary-adrenal and renin-angiotensin
      aldosterone systems, skin spotty pigmentation, neoplasms in the viscera, skin,
      and fat. These specific features emphase the predictive value of the myxomal
      syndrome, which predetermines that its early diagnosis should be made in routine
      clinical practice.

PMID- 7519930
TI  - [The problem of detection of pathogenic microorganisms in sperm].

PMID- 7519931
TI  - [Activity of the Academy of Medical Sciences of the USSR during World War II and
      early postwar years (50th anniversary of the foundation of the Russian Academy of
      Medical Sciences)].

PMID- 7519932
TI  - [Methods of treatment of acute hepatic insufficiency with isolated hepatocytes].
AB  - The paper describes different methods for using isolated hepatocytes to
      compensate hepatic dysfunctions and to treat hepatic failure. Most of them are
      safe and produce no complications if isolated hepatocytes are separated from
      blood with the semipermeable membrane. The survival and functional activity of
      isolated hepatocytes transplanted into different places and organs are ambiguous
      and unequal in terms of efficiency. Search for a rational and optimal method for
      implantation of isolated hepatocytes, for conditions for their functioning, for
      combinations of different cells, for proliferation of the implanted cells is a
      subject of special interest and it is in progress. Many procedures have been
      experimentally justified and are being now used clinically to treat hepatic
      failure in various hepatic diseases.

PMID- 7519933
TI  - [Digestive functions of the rodent forestomach].

PMID- 7519934
TI  - Hepatitis C virus infection and liver disease after allogeneic bone marrow
      transplantation.
AB  - We tested the sera of 29 patients treated with allogeneic bone marrow
      transplantation (BMT) by first- and second-generation ELISAs for hepatitis C
      virus (HCV) antibodies to study the effect of HCV infection on post-transplant
      liver diseases. Before BMT the first-generation assay detected anti-HCV in 3 of
      29 patients (10%) and the second-generation assay detected anti-HCV in 5 of 29
      (17%). After BMT the first-generation assay detected anti-HCV in 11 of 20
      patients (55%) and the second-generation assay detected anti-HCV in 14 of 20
      (70%). According to pre-transplant anti-HCV status by the second-generation
      assay, liver failure occurred in none of the anti-HCV-positive group and three of
      the anti-HCV-negative group. Graft-versus-host disease was responsible for liver
      failure in these patients. According to the post-transplant anti-HCV status by
      the second-generation assay, chronic hepatitis was found in 14 of 14 (100%) anti
      HCV-positive and 1 of 6 (17%) anti-HCV-negative patients during post-transplant
      follow-up (p < 0.001). Post-transplant seroconversion from anti-HCV-negative to
      anti-HCV-positive status assay was detected by the second-generation assay in 9
      of 20 (45%) patients. A biochemical deterioration during seroconversion was
      observed in 7 of 9 (79%) cases. HCV plays an important role in the etiology of
      post-transplant liver disease.

PMID- 7519935
TI  - Phenotypic differences of CD34-positive stem cells harvested from peripheral
      blood and bone marrow obtained before and after peripheral blood stem cell
      collection.
AB  - Using two-color flow cytometry, we analyzed the subpopulations of CD34+ stem and
      progenitor cells in the blood and bone marrow from 10 patients with hematological
      malignancies. Peripheral blood mononuclear cells (PBMNC) harvested after
      chemotherapy (high-dose Ara C and VP-16) and rhG-CSF, and BM mononuclear cells,
      which were obtained before chemotherapy (BMMNCbefore) and after the stem cell
      collection (BMMNCafter) were isolated by Ficoll-Hypaque centrifugation. The
      purified cells were stained with FITC-conjugated anti-CD34 antibody and one of
      the following PE-conjugated antibodies: anti-CD7, CD10, CD11b, CD11c, CD13, CD19,
      CD33, CD38, CD45RO, CD56, and HLA-DR. CD34+ PBMNC harvested and the CD34+
      BMMNCafter expressed CD13 and CD33 more frequently than CD34+ BMMNCbefore but
      expressed CD10 and CD19 less frequently than CD34+ BMMNCbefore. These data
      suggested that harvested PBMNC contain more myeloid lineage committed progenitors
      than BMMNCbefore, which might contribute to the rapid recovery of neutrophils
      after peripheral blood stem cell transplantation. No significant phenotypic
      differences of CD34+ cells between harvested PBMNC and BMMNCafter were observed
      except for the expression of CD11c. CD34+ PBMNC harvested coexpressed CD11c more
      frequently than both CD34+ BMMNCbefore and CD34+ BMMNCafter, which expression
      might be associated with commitment to the monocyte lineage.

PMID- 7519936
TI  - Phase I study of in vivo lenograstim (rHuG-CSF) for stem cell collection
      demonstrates improved neutrophil recovery after autologous bone marrow
      transplantation.
AB  - Colony stimulating factors and especially rHuG-GSF, the first available
      neutrophil growth factor, have led to considerable interest in the field of stem
      cell transplantation because of their ability to induce stem cell
      peripheralization either alone or in association with high-dose chemotherapy. Few
      data exist, however, on the impact of rHuG-CSF on large scale bone marrow
      collection and autologous bone marrow transplantation (ABMT). This phase I, non
      randomized, dose escalation study of rHu-G-CSF (lenograstim) administered to 30
      patients at doses ranging from 1 to 40 micrograms/kg/day for 5 days before bone
      marrow harvesting showed that priming with rHu-G-CSF in vivo increased the number
      of bone marrow cells and D14 myeloid restricted progenitors (CFU-GM) and led to a
      better neutrophil recovery after ABMT compared with a contemporary unprimed
      control population. Otherwise, this study established that 5 days of rHuG-CSF
      therapy, as a sole stimulus, induced a tenfold increase in the circulating CFU-GM
      amongst which immature progenitors, estimated by the Delta assay (secondary CFU
      GM grown after 7 days of liquid culture/primary CFU-GM), are detected. These
      conclusions were valid for doses as low as 2 micrograms/kg/day which induced only
      mild neutrophilia up to the highest dose (40 micrograms/kg/day) and suggest that
      a short course of rHuG-CSF is beneficial in increasing the stem cell collection.

PMID- 7519938
TI  - Large-scale preparation of highly purified, frozen/thawed CD34+, HLA-DR-
      hematopoietic progenitor cells by sequential immunoadsorption (CEPRATE SC) and
      fluorescence-activated cell sorting: implications for gene transduction and/or
      transplantation.
AB  - The purification of early hematopoietic progenitor cells for autologous
      transplantation is based on two rationales: (1) elimination of clonogenic tumor
      cells, and/or (2) gene transfer into indefinitely self-replicating hematopoietic
      stem cells. Primitive CD34+ stem cells can be separated from more mature stem
      cells, or probably from clonogenic tumor cells, by differences in HLA-DR surface
      antigen expression. The objective of this study was to establish a large-scale
      technique for purification of CD34+, DR- progenitor cells from a large volume
      marrow harvest. In five different experiments, CD34+ cells were purified to
      between 76% and 91% by avidin-biotin immunoadsorption (CEPRATE SC) as a first
      step. This was followed by fluorescence-activated cell sorting to separate DR+
      and DR- cells, which resulted in the generation of between 1.75 and 11.3 x 10(5)
      CD34+, DR- cells. The purity of DR- cells increased from between 0.5% and 4.3% in
      the immuno-adsorbed fraction up to 99% in the DR- sorted fraction. As shown in a
      single experiment, the purity of CD34+, DR- cells immediately after thawing
      increased from 0.01% to 94.3% while losing 99% of those early progenitor cells
      during the multistep purification procedure. We were able to physically separate
      one CD34+, DR- cell from up to 8000 nucleated cells in the prepurified cell
      suspension. One million highly purified CD34+, DR- progenitor cells is
      potentially an adequate cell dose for autologous transplantation equivalent to
      what is contained in an unselected and functioning marrow autograft.

PMID- 7519937
TI  - XomaZyme-CD5 immunotoxin in conjunction with partial T cell depletion for
      prevention of graft rejection and graft-versus-host disease after bone marrow
      transplantation from matched unrelated donors.
AB  - Patients who receive bone marrow transplants from unrelated donors have a high
      incidence of graft-versus-host disease (GVHD). If the donor marrow is first T
      cell-depleted, the everity of GVHD declines but the risk of rejection rises. In
      an attempt to prevent both graft rejection and GVHD, we included an anti-T cell
      antibody-toxin conjugate (CD-5-Ricin; XomaZyme H65) in the transplant
      conditioning regimen. After receiving a partially T cell-depleted marrow,
      patients then received a second course of immunotoxin as additional GVHD
      prophylaxis. Eight recipients of unrelated donor marrow transplants were studied.
      All engrafted (ANC > 500 x 10(6)/l by day 15, range 13-20 days). One patient had
      grade II skin GVHD and one developed grade IV disease but the other six patients
      had no acute GVHD. However, there was high morbidity and mortality from virus
      infections associated with a sluggish return of CD4 and CD8 T cells into the
      normal range. Four patients died from virus disease (CMV, n = 2; EBV, n = 1;
      adenovirus, n = 1) and the remaining patients had frequent documented viral
      illnesses during the first year. We conclude that improvement in the outcome of
      unrelated donor marrow transplantation will require strategies which prevent
      rejection and GVHD coupled with attempts to accelerate immune reconstitution.

PMID- 7519940
TI  - Influence of G-CSF on NK cell recovery after autologous BMT.

PMID- 7519941
TI  - Proteolipid protein gene dosage effect in Pelizaeus-Merzbacher disease.

PMID- 7519939
TI  - Correction of neutropenia with rHuG-CSF after loss of response to rHuGM-CSF
      following autologous bone marrow transplant.
AB  - We describe a patient who presented with graft failure following autologous BMT,
      with an initial response of the neutrophil count to rHuGM-CSF but eventual loss
      of this response. Subsequently, this patient responded to rHuG-CSF. This could be
      explained by the fact that rHuG-CSF stimulates both early and late myeloid
      progenitor cells whereas rHuGM-CSF stimulates mainly the intermediate myeloid
      progenitor cells. This finding suggests that rHuG-CSF should be investigated for
      the treatment of patients with graft failure following ABMT.

PMID- 7519942
TI  - Role of polyadenylated RNA sequences (POLADS) in vaccinia virus infection:
      correlation between accumulation of POLADS and extent of shut-off in infected
      cells.
AB  - The selective inhibition of host-cell protein synthesis was studied in cells
      infected with vaccinia virus (VV) under aberrant conditions of transcription.
      Previous studies in our laboratory have correlated this selective inhibition with
      a class of short polyadenylated virus-directed RNAs (POLADS) which are
      synthesized in VV-infected cells during the early phase of transcription.
      Moreover, it was shown that infection of HeLa cells with UV-irradiated VV or
      infection in the presence of actinomycin D (ACD) amplifies the synthesis of
      POLADS compared to the amount produced in cells infected under normal conditions.
      To further study the role of POLADS in shut-off, we utilized a temperature
      sensitive mutant of VV which induces only marginal host shut-off at the
      restrictive temperature. POLADS were isolated from cells infected with either
      unirradiated or UV-irradiated VV ts mutant at the permissive and restrictive
      temperatures and their inhibitory activity on translation in vitro was assayed.
      The study yields further evidence associating excess of POLADS with greater
      inhibitory potential and supports the speculation that the increased production
      of POLADS is correlated with the inhibition of translation of both host-cell and
      viral polypeptides, albeit to different degrees. The results also demonstrate
      that a lack of POLADS accumulation is related to a corresponding reduction of
      shut-off.

PMID- 7519943
TI  - Reprogramming of nucleolar gene expression during the acclimatization of the
      carp.
AB  - During seasonal acclimatization of eurythermal fish, the nucleolus of the
      hepatocyte undergoes ultrastructural reprogramming. In winter acclimatized carp,
      the nucleolar components are segregated, a condition that suggests a decreased
      transcription of rRNA. The same nucleolar reorganization was observed when
      pituitary cells from winter- and summer-acclimatized carp were examined. In situ
      analyses of nucleolar RNA revealed a marked lowering of RNA content in the
      segregated nucleoli. Accordingly, in vitro synthesis of RNA was shown to be
      significantly lower in pituitary tissue from cold-acclimatized fish where
      precursor accumulated. Conversely, in pituitary tissue from summer-adapted fish
      the rate and extent of synthesis and of rRNA processing was notably higher. The
      involvement of pre-rRNA processing events during seasonal acclimatization was
      corroborated by the strong differences of U3 RNA content detected by in situ
      hybridization in pituitary cells from summer- and winter-fish. When RNA
      polymerase I activity from both acclimatized states were assayed, no differences
      were detected. Thus, it appears that in fish RNA polymerase I itself does not
      play an important role in the control of nucleolar gene expression and the
      nucleolar gene expression reprogramming that the seasonal rearrangement
      represents might involve, among the many nucleolar-specific proteins,
      transcription factors.

PMID- 7519945
TI  - New visions for professional development.

PMID- 7519944
TI  - Public awareness of prostate cancer and the prostate-specific antigen test.
AB  - Prostate cancer and prostate-specific antigen (PSA) testing have been the focus
      of significant media attention. This study examines the public's knowledge of
      prostate cancer, knowledge of the PSA test, and among men, the use of the test.
      The data are from the 1993 Kentucky Health Survey, an annual probability-based
      statewide telephone survey of adult (18 years of age and older) Kentucky
      residents (n = 661). Although 92% of the sample reported hearing of prostate
      cancer, the respondents were basically uninformed about the outcomes of prostate
      cancer. Men 50 years of age and older were no more informed than was the rest of
      the sample about prostate cancer or PSA testing. However, 94% of the men who had
      the test recommended by their physician had undergone the test. These findings
      indicate that adults remain poorly informed about prostate cancer and possible
      case-finding strategies. If the American Cancer Society's (ACS) early detection
      recommendations are to succeed, attention should focus on improving the public's
      awareness of currently available methods for early detection of prostate cancer.

PMID- 7519946
TI  - Nitric oxide mediates the hypertensive response to a modified hemoglobin solution
      (DCLHb) in rats.
AB  - We investigated the effect of nitric oxide synthase inhibition with L-NAME, and L
      arginine (nitric oxide synthase substrate), on the hemodynamic response to a
      modified hemoglobin solution (DCLHb). Rats were given one of the following
      regimens (all groups hypervolemic except Control): Control-8.0 ml of donor blood
      (isovolemic exchange); HV-8.0 ml of donor blood; DCLHb-8.0 ml of DCLHb; L-NAME-30
      mg.kg-1 of L-NAME followed by 8.0 ml of DCLHb; or L-Arg-8.0 ml of DCLHb followed
      by L-arginine (600 mg.kg-1). Mean arterial blood pressure (MABP) was continuously
      recorded and the change compared to baseline and expressed as delta MABP. delta
      MABP was greater in the HV and DCLHb groups versus the Control and L-NAME groups;
      and was greater in the DCLHb group versus the HV group. delta MABP was not
      different between the Control and L-NAME group. In the L-Arg group the initial
      delta MABP (after DCLHb) was similar to the DCLHb group; however, after L
      arginine administration delta MABP was not different from the Control group. This
      study supports a hypothesis that DCLHb effects an increase in MABP by a nitric
      oxide related mechanism.

PMID- 7519949
TI  - Blepharophimosis, ptosis and mental retardation: further delineation of Ohdo
      syndrome.
AB  - The Ohdo syndrome is characterized by blepharophimosis, ptosis, abnormal ears,
      and mental retardation. This report describes a child with the Ohdo syndrome who,
      in addition, has microcephaly and growth retardation. Her phenotype probably
      represents variable expression or genetic heterogeneity of the Ohdo syndrome.

PMID- 7519947
TI  - Bio-histochemical aspects of integrins (alpha 2 beta 1, alpha 6 beta 1) in
      invasive mammary carcinomas: an immunohistochemical study.
AB  - Immunohistochemical expression of integrins was examined in 39 human invasive
      mammary carcinomas, of which 34.2% and 43.6% expressed integrins alpha 2 beta 1
      and alpha 6 beta 1, respectively. Immuno-electron microscopy clearly demonstrated
      that the integrins were in the cell membrane of the carcinoma cells. Similar
      expression of integrin alpha 2 beta 1 or alpha 6 beta 1 in both the intraductal
      component and invasive portion of the same tumor was seen in 76.9% and 85.7% of
      cases, respectively. This suggested that invasive carcinoma cells retained their
      integrin expression after invasion through the basement membrane. Reciprocal
      expression of integrins alpha 2 beta 1 and alpha 6 beta 1 was seen in 20 cases.
      Expression of alpha 2 beta 1 was seen significantly less frequently in scirrhous
      carcinoma than in the more differentiated papillotubular or solid tubular
      carcinoma (Chi-squared test, P < 0.05). Intraductal components of carcinoma were
      present more frequently in cases expressing integrin alpha 2 beta 1 than in those
      that were negative. This suggests the potential usefulness of integrins as
      clinical parameters in the surgical treatment of mammary carcinoma, since recent
      trials of conservative treatment for mammary carcinoma have focused on the
      intraductal spread of the tumor cells.

PMID- 7519948
TI  - Self-reported wheezing and allergic rhinitis in children and traffic density on
      street of residence.
AB  - A survey of 2050 seventh- and eighth-grade schoolchildren was conducted in
      Bochum, Germany, in 1991. The prevalence of wheezing and allergic rhinitis was
      assessed by self-completed written questionnaires and video questionnaires. To
      estimate the traffic density on the street of residence, children were asked
      about the frequency of heavy truck traffic on weekdays and to describe the street
      either as a main road or as a side street. There was a positive correlation
      between the prevalence of wheezing as well as allergic rhinitis and the
      indicators of traffic density, controlling for age, sex, nationality, passive
      smoking, active smoking, parental history of asthma, and so on. The adjusted
      prevalence odds ratio (ORs) and 95% confidence intervals (CIs) contrasting the
      "frequent" and "constant" categories for truck traffic with the "never" category
      were as follows: for wheezing (written questionnaire), OR = 1.53 (CI: 1.06 to
      2.20) and OR = 1.67 (CI: 1.05 to 2.66); for wheezing (video questionnaire), OR =
      1.58 (CI: 1.13 to 2.20) and OR = 1.94 (CI: 1.26 to 2.99); and for allergic
      rhinitis, OR = 1.67 (CI: 1.17 to 2.38) and OR = 1.54 (CI: 0.97 to 2.44). In
      conclusion, a possible role of factors associated with automobile exhausts
      causing or exacerbating asthma symptoms and allergic rhinitis in children is
      supported.

PMID- 7519950
TI  - Megalocornea, developmental retardation and dysmorphic features: two further
      patients.
AB  - Two unrelated children are described with megalocornea, mild-moderate
      developmental delay, mild joint laxity and a similar dysmorphic appearance,
      comprising a bossed forehead, hypertelorism, a saddle-shaped nose and a carp
      shaped mouth with prominent lips. Similar abnormalities have been observed in
      previously reported cases of megalocornea/mental retardation and may help to
      define one subtype of this heterogeneous group of conditions.

PMID- 7519951
TI  - Epinephrine-induced ventricular premature complexes due to early
      afterdepolarizations and effects of verapamil and propranolol in a patient with
      congenital long QT syndrome.
AB  - We report a patient with congenital long QT syndrome in whom early
      afterdepolarizations (EADs) were demonstrated on monophasic action potential
      (MAP) recordings in the left ventricular mid-base inferior wall. Epinephrine
      infusion at 5 micrograms/min increased the amplitude of the EADs and the late
      component of the T(U) wave. Epinephrine also induced ventricular premature
      complexes (VPCs) with right bundle branch block morphology and left-axis
      deviation that occurred from the peak of the EADs. Verapamil injection (5 mg)
      during continuous epinephrine infusion abolished all VPCs with a slight reduction
      in the amplitude of the EADs. Propranolol injection (5 mg) in addition to
      verapamil further reduced the amplitude of the EADs and the late component of the
      T(U) wave. These findings suggest that the epinephrine-induced VPCs were closely
      related to triggered rhythm arising from the EADs, and that both verapamil and
      propranolol were effective for the suppression of VPCs and EADs.

PMID- 7519952
TI  - Pathophysiology of gap junctions in heart disease.
AB  - Electrical coupling between cardiac muscle cells is mediated by specialized sites
      of plasma membrane interaction termed gap junctions. These junctions consist of
      clusters of membrane channels that directly link the cytoplasmic compartments of
      neighboring cells. Each gap-junctional channel consists of two connexons, one
      from each of the interacting plasma membranes, extending across the narrow
      extracellular gap. Connexons are constructed from connexins, a multigene family
      of conserved proteins. Different connexins confer specific electrophysiologic
      characteristics on the assembled channel protein. The major connexin of the
      mammalian heart is connexin43, although other types of connexins are also
      expressed, notably connexin40 in myocytes of the atrioventricular conduction
      system. Confocal laser scanning microscopy of anti-connexin43 immunolabeled
      samples reveals two major abnormalities in myocardial gap junctions in ischemic
      heart disease: loss of the usual ordered distribution of gap junctions at border
      zones adjacent to infarct scars, and reduction in the quantity of connexin43 gap
      junctions in myocardium distant from the infarct. These and other changes
      reported in myocardial gap-junctional communication pathways following infarction
      may result in heterogeneous anisotropic conduction and reduced conduction
      velocity, thereby forming a proarrhythmic substrate. Current evidence suggests
      that reduction in connexin43 content is a general pathogenetic feature of cardiac
      disease, and that changes in the expression levels of other connexin types may
      contribute to altered electrophysiologic function in the diseased heart.

PMID- 7519953
TI  - Selective planting of cationized, haptenized ovalbumin on the rat tubular
      basement membrane.
AB  - We developed an experimental protocol for planting exogenous antigens with
      different molecular weights and charges on the constituents of the renal
      tubulointerstitium. The cationized antigens were injected selectively into the
      left renal arteries of Wistar rats. Antigen localization was documented by
      immunohistochemistry on frozen sections. Cationized bovine serum albumin (BSA; 68
      kDa, isoelectric point = 9.5) localized almost exclusively along the glomerular
      capillary wall. After application of highly cationic polyethyleneimine,
      cationized BSA given subsequently was found in a linear distribution along the
      glomerular capillary wall and along the peritubular capillaries. The fate of
      highly cationized ovalbumin conjugated with trinitrophenol (TNP-OA), subjected to
      gel filtration to obtain monomers (42 kDa, isoelectric point > 10) differed; it
      was deposited in a linear pattern on the tubular basement membrane (TBM) and
      Bowman's capsule, and remained up to 36 h after injection. Noncationized,
      monomeric TNP-OA (42 kDa, isolectnic point = 4.6) showed fine granular deposition
      in the tubular epithelium exclusively. These findings indicate that the barrier
      of the glomerular BM acts selectively on antigens with different molecular
      weights. They either settle on the peritubular capillaries, after passing the
      glomerular, or reach the urinary space, after which they are reabsorbed by the
      tubular epithelial cells to reach the TBM.

PMID- 7519954
TI  - KP-1: not a specific marker. Staining of 137 sarcomas, 48 lymphomas, 28
      carcinomas, 7 malignant melanomas and 8 cystosarcoma phyllodes.
AB  - This study documents the reactions of the monoclonal antibody KP-1, which detects
      histiocytes in paraffin sections, with 137 sarcomas, 48 lymphomas, 28 carcinomas,
      7 malignant melanomas and 8 cystosarcoma phyllodes. The soft tissue sarcomas had
      been previously immunophenotyped. Positive staining was obtained in all
      categories of sarcoma except clear-cell sarcomas. Most categories of sarcoma
      showed staining in less than 10% of tumour cells although a minority of
      leiomyosarcomas showed more extensive staining. Five of 7 malignant melanomas
      were also positive while all lymphomas and carcinomas were negative. We conclude
      that KP-1 positivity is not helpful in supporting the histiocytic origin of a
      tumour and is of limited value in the differential diagnosis of soft tissue
      sarcomas or their separation from other categories of malignancy.

PMID- 7519955
TI  - High free and latent collagenase activity in psoriatic arthritis synovial fluids.
AB  - Collagenase activity has been studied intensively in SF from OA and RA patients.
      Less is known about collagenolytic activity in PsA SF. Therefore we examined
      collagenolytic activity in crude and trypsin treated SF as well as the alpha 1
      antitrypsin and alpha 2-macroglobulin concentrations in 50 patients suffering
      from OA (n = 13), RA (n = 17), and PsA (n = 20). Free collagenolytic activity was
      low in the crude OA SF (1.80 +/- 1.35 micrograms released collagen/min/ml SF) and
      almost equally low in RA SF (2.35 +/- 1.80 micrograms released collagen/min/ml
      SF; P > 0.3). The PsA SF, however, exhibited a significantly higher free
      collagenolytic activity (5.63 +/- 5.69 micrograms released collagen/min/ml SF; P
      < 0.05 in comparison to OA and RA SF). The treatment of the SF with trypsin
      further activated collagenolytic activity in each group (OA 2.17 +/- 1.35
      micrograms released collagen/min/ml SF; RA 6.48 +/- 6.73 micrograms released
      collagen/min/ml SF; PsA 11.24 +/- 5.02 micrograms released collagen/min/ml SF)
      and yielded significant differences between OA and RA, OA and PsA, and RA and PsA
      SF (P < 0.05). Concomitantly with the collagenolytic activity, the alpha 1
      antitrypsin and alpha 2-macroglobulin concentrations of the SF were measured. In
      SF from patients with PsA (172.9 +/- 69.4 mg/100 ml) and RA (190.6 +/- 64.7
      mg/100 ml) the alpha 1-antitrypsin was significantly higher than in those from OA
      SF (106.1 +/- 39.2 mg/100 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519956
TI  - Antibodies to synthetic peptide P62 corresponding to the major epitope of
      rheumatoid arthritis nuclear antigen in a west African population with rheumatoid
      arthritis.
AB  - Using a synthetic peptide (P62) we have investigated antibodies to rheumatoid
      arthritis nuclear antigen (RANA) in 58 West African patients with RA, 51 with
      malaria, 111 with tuberculosis (TB) and 166 healthy controls by ELISA using a
      synthetic peptide (P62). As in Western populations the RA sera showed
      significantly increased levels of anti-P62 antibodies though in our study the
      mean titres were only elevated twofold above the controls. The levels in malaria
      and TB were normal. Our data extend previous work by showing that raised anti-P62
      antibodies is a consistent finding in RA world-wide including indigenous West
      African patients.

PMID- 7519958
TI  - Endoscopic palliation of esophageal carcinoma.
AB  - Endoscopic palliation of unresectable esophageal carcinoma includes techniques of
      dilation, esophageal intubation, laser ablation, and intraluminal brachytherapy.
      Indications, advantages, disadvantages, results, and complications of these
      methods are discussed. Less common techniques include electrocoagulation,
      chemical necrolysis, and photodynamic therapy. Prospective randomized trials
      comparing techniques are reviewed. The thoracic surgeon must be acquainted with
      several endoscopic means of palliation in order to meet the needs of the
      individual patient.

PMID- 7519957
TI  - Keratin 19-like immunoreactivity in receptor cells of mammalian taste buds.
AB  - Three monoclonal antibodies, 4.62, LP2K and 170.2.14, were used to evaluate
      keratin 19-like immunoreactivity in gustatory epithelia. Keratin 19-like
      immunoreactivity was restricted to the intragemmal cells for all types of
      mammalian taste buds examined. These taste buds included fungiform, foliate and
      vallate taste buds in rat, gerbil and rabbit, and nasopalatine, epiglottal and
      palatine taste buds in rat. There was no keratin 19-like immunoreactivity in
      basal cells or in perigemmal cells lateral to the immunoreactive taste receptor
      cells. Denervation of the rat vallate papilla eliminated all taste buds, as well
      as all immunoreactive taste cells. That the immunoreactive material in the taste
      cells was keratin 19 was supported by the comparable staining of rat taste buds
      with each of three monoclonal antibodies specific for keratin 19. Furthermore, as
      predicted, these antibodies selectively stained luminal cells of rat bile ducts,
      bladder, salivary ducts, trachea, ureter and uterus. It was concluded that
      monoclonal antibodies against keratin 19 can usefully distinguish intragemmal
      taste receptor cells from keratinocytes, and from the perigemmal and basal cells
      of gustatory epithelia. Anti-keratin 19 antibodies may serve to identify
      differentiated taste cells in gustatory epithelia undergoing taste bud
      development, renewal, degeneration or regeneration.

PMID- 7519959
TI  - Mediastinal germ cell tumors. A continuing odyssey.
AB  - Mediastinal germ cell tumors are rare, and in the past they were uniformly
      lethal. A high index of suspicion leading to early diagnosis combined with modern
      interdisciplinary management can now prolong comfortable survival and produce
      many cures. The development of Cis-Platinum based combination chemotherapy, and
      its early use, has been the major factor in the improvement of treatment results.

PMID- 7519960
TI  - The mutability of low-affinity nerve growth factor receptor (p75NGFR) expression
      in the rat cuneate nucleus following perinatal injury and adult deafferentations:
      comparisons with cytochrome oxidase.
AB  - In normal adult rats, intense immunostaining for the 75 kDa low-affinity receptor
      for nerve growth factor and other neurotrophins (p75NGFR) is concentrated in the
      middle region of the cuneate nucleus (CN), distributed in a blotchy pattern
      similar to that of cytochrome oxidase (CO) activity. In the adult rats, partial
      dorsal rhizotomies (centered around the 7th and 8th cervical spinal segments)
      resulted in the complete disappearance of p75NGFR-like immunoreactivity within
      the ipsilateral CN, but did not affect the distribution of the CO blotches.
      Perinatal (postnatal day 1-8) damage to the ipsilateral forepaw and subsequent
      rearing to adulthood also resulted in significant disruption of the topographical
      expression of p75NGFR-like immunoreactivity within the CN, as well as--as
      previously reported--disruption of the CO blotches. Although the patterns of
      staining in intact adult rats are similar for CO staining and for p75NGFR-like
      immunoreactivity within the CN, the CO staining appears to be primarily
      associated with postsynaptic cells, while the p75NGFR-like immunostaining appears
      to be associated with primary afferent terminals.

PMID- 7519961
TI  - Localization of striatal and nigral tachykinin receptors in the rat.
AB  - The effects of lesioning mesostriatal dopamine projections or striatal neurons on
      tachykinin binding in the basal ganglia were assessed in the rat. 6
      Hydroxydopamine lesions of the medial forebrain bundle destroyed striatal
      dopamine terminals as assessed by [3H]mazindol autoradiography, but did not
      significantly affect the binding of NK-1 ([3H][Sar9,Met(O2)11]substance P) or NK
      3 ([3H]senktide) tachykinin ligands in the striatum. 6-Hydroxydopamine lesions
      significantly reduced NK-3 binding in the substantia nigra pars compacta, but not
      the ventral tegmental area. In contrast, striatal quinolinic acid lesions reduced
      both NK-1 and NK-3 binding in the striatum, but failed to affect NK-3 binding in
      the substantia nigra. These findings suggest that both NK-1 and NK-3 receptors
      within the striatum are predominantly post-synaptic with respect to dopamine
      neurons, whereas nigral NK-3 receptors are located on dopaminergic neurons.

PMID- 7519962
TI  - Effects of nitric oxide synthase inhibitors on N-methyl-D-aspartate-induced phase
      delay of circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus
      in vitro.
AB  - Excitatory amino acid (EAA) receptors such as N-methyl-D-aspartate (NMDA) and non
      NMDA receptors have been suggested to play an important role in the regulation of
      photic information from the retina to the suprachiasmatic nucleus (SCN).
      Therefore, we investigated the role of glutamate as a retinohypothalamic
      transmitter by analyzing the phase-resetting effects of NMDA and a non-NMDA
      agonist, (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA),
      on the circadian rhythm of SCN firing activity. Nitric oxide (NO) production is
      believed to be an essential intermediate in NMDA-induced cGMP production in the
      CNS. Thus, we examined the effects of blockers of NO production on NMDA- or AMPA
      induced phase delay of SCN activity rhythm. N-nitro-L-arginine methylester (L
      NAME) blocked NMDA- but not AMPA-induced phase shift, indicating the involvement
      of NO synthesis in NMDA-induced phase changes. L-arginine but not D-arginine
      caused a phase delay, and L-NAME blocked L-arginine-induced phase delay. In
      addition, cotreatment with NMDA and L-arginine did not have an additive effect.
      These results suggest that NO production itself is involved in the phase change
      of SCN neuron activity, and NMDA-induced phase changes are also mediated via
      activation of NO synthesis in this nucleus.

PMID- 7519963
TI  - Morphological and electrophysiological analysis of the peripheral and central
      afferent pathways from the clitoris of the cat.
AB  - Afferent neurons projecting to the clitoris of the cat were identified by WGA-HRP
      tracing in the S1 and S2 dorsal root ganglia. An average of 433 cells were
      identified on each side of the animal. 85% and 15% of the labeled cells were
      located in the S1 and S2 dorsal root ganglia, respectively. The average cross
      sectional area of clitoral afferent neuron profiles was 1,479 +/- 627 micron2.
      Unilateral transection of the pudendal nerve reduced the number of labeled cells
      to 1% of that on the control side. Central projections of clitoral afferents were
      identified in the lumbo-sacral segments (L7-S3) of the spinal cord. HRP labeled
      fibers were located in the marginal zone on the medial side of dorsal horn and
      extended into the dorsal half of the dorsal gray commissure. Electrophysiological
      recordings detected axonal volleys in the pudendal nerve and S1 dorsal root in
      response to electrical stimulation (threshold, 1-4 V) of the clitoral surface.
      Estimated axonal conduction velocities at the two sites ranged from 7-27 m/s and
      0.6-30 m/s, respectively. Multi-unit recordings from dorsal roots in the lumbo
      sacral segments revealed that non-noxious pressure stimulation of the clitoris
      evoked discharges in the S1 dorsal root. Small increases were also detected in
      the S2 and L7 roots. Single unit discharges recorded from S1 dorsal roots were
      activated by electrical stimulation of the clitoral surface at thresholds of 0.6
      1.2 V and latencies of 1.5-1.8 ms (estimated conduction velocities of 24-30
      m/s.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7519964
TI  - Evidence for connections between a discrete hypothalamic dorsochiasmatic area and
      the supraoptic and paraventricular nuclei.
AB  - In order to check the existence of direct or indirect connections between the
      hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, four retrograde
      traces were iontophoretically injected into these nuclei. The small injection
      sites were restricted to parts of the SON and PVN, enabling the identification of
      afferent neurons localized in their immediate vicinity. The tracer injections
      into any of these hypothalamic nuclei resulted in conspicuous labeling of cells
      gathered dorsally to the optic chiasma and the optic tract. This neuronal
      population was tentatively called dorsochiasmatic area. Double retrograde tracers
      injections into the ipsilateral SON and PVN gave evidence for some neurons
      containing both tracers in this dorsochiasmatic area. Otherwise, labeled
      parvocellular neurons were occasionally found in one PVN, after injecting
      retrograde tracer into either the ipsilateral SON or the contralateral PVN. As
      few connections exist between the four magnocellular nuclei, the dorsochiasmatic
      area connected with both the ipsilateral SON and PVN could play an important role
      in regulating the oxytocin and/or vasopressin systems.

PMID- 7519965
TI  - Developing a poster about a clinical innovation. Part II: Creating the poster.
AB  - This is the second in a series of three articles developed to assist the CNS in
      planning, producing, and presenting a clinical poster. The purpose of a poster
      and critical steps in producing the poster are described in this article. The
      process of producing the poster is driven by space limitations and the main
      purpose of the presentation; whether the poster is produced by the presenter or a
      professional is determined by the presenter's preference and resources. Special
      focus is upon the units of the layout, how the units are produced, and how they
      are put together.

PMID- 7519966
TI  - Desmoid tumors in patients with familial adenomatous polyposis.
AB  - BACKGROUND: Sporadic desmoid tumors occur mainly in the abdominal wall and in
      extraabdominal sites. Desmoid tumors in patients with familial adenomatous
      polyposis (FAP) usually occur in the abdominal wall and in the bowel mesentery.
      Surgical resection of desmoids in patients with FAP has been controversial.
      METHODS: A retrospective review of patients with FAP and desmoid tumors treated
      from 1950 to 1991 was performed. Patients were evaluated for gender, age, site of
      desmoid tumors, treatment, recurrence, and survival. RESULTS: Twenty-one of 24
      patients underwent 60 surgical procedures related to the desmoid tumors. Seven of
      nine patients who underwent potentially curative surgery had recurrences; three
      were reresected. Major morbidity after palliative or curative surgery was 47%.
      Five patients were alive with no evidence of disease at a median of 198 months,
      10 patients were alive with disease at a median of 102 months, and 5 patients
      died with disease at a median of 31 months after diagnosis. CONCLUSIONS: Desmoid
      tumors are common in patients with FAP. Unresectability and recurrence are more
      common than cure. Palliative and curative resections have a high morbidity.
      Surgery should be reserved for those patients with symptomatic mesenteric
      desmoids.

PMID- 7519967
TI  - A radiologic syndrome after high dose chemotherapy and autologous bone marrow
      transplantation, with clinical and pathologic features of systemic candidiasis.
AB  - BACKGROUND: The use of high dose chemotherapy in the treatment of solid tumors is
      associated with prolonged neutropenia and, consequently, in some patients,
      systemic candidiasis. The authors describe their experience with a
      clinicoradiologic syndrome developing after high dose chemotherapy was
      administered to patients with breast cancer. METHODS: The authors evaluated the
      clinical and radiologic records of 12 patients in whom hepatic, splenic, or renal
      candidiasis developed. RESULTS: Three patients had positive blood cultures for
      candida tropicalis. One of these patients and two others had fungal organisms
      identified with special stains of an organ aspirate. Most patients were
      asymptomatic, and most of them were treated successfully with antifungal agents,
      although untreated patients also recovered. There were no fatalities due to the
      candidiasis. CONCLUSIONS: A radiographic syndrome resembling hepatic, splenic, or
      renal candidiasis is described, which occurred after high dose chemotherapy was
      administered and autologous bone marrow transplantation was performed on patients
      with breast cancer. This syndrome has a favorable prognosis. Conclusions as to
      the more indolent nature of this syndrome cannot be made; however, this topic
      warrants further investigation.

PMID- 7519969
TI  - Merkel cell distribution in human hair follicles of the fetal and adult scalp.
AB  - The distribution of Merkel cells in fetal and adult terminal hair follicles of
      human scalp was studied immunohistochemically using cytokeratin (CK) 20 as a
      specific Merkel cell marker. In hair follicles of adult scalp, abundant Merkel
      cells were found enriched in two belt-like clusters, one in the deep infundibulum
      and one in the isthmus region. No Merkel cells were found in the deep follicular
      portions including the bulb, or in the dermis. In early fetal hair follicles
      (bulbous peg stage), Merkel cells were only detected in the basal layer of the
      developing infundibulum but not in deeper follicular areas. In later stages,
      Merkel cells were also present in the isthmus and bulge. No Merkel cells were
      seen in the dermis around developing hair follicles. Nerve growth factor receptor
      was not only present in nerves but was found to be widely distributed within
      fetal skin. In adult skin, this receptor was localized to the basal cell layers
      of the outer root sheath of the bulb and the suprabulbar area, but was not
      detectable in the areas containing Merkel cells. The present study localizing
      Merkel cells within the permanent hair follicle structures close to their
      possible stem cells suggests that they have paracrine functions.

PMID- 7519968
TI  - Keratin expression: a measure of phenotypic modulation of human prostatic
      epithelial cells by growth inhibitory factors.
AB  - Expression of certain cytokeratins can be indicative of the state of
      differentiation of epithelial cells. The basal cells in the normal adult human
      prostatic epithelium are characterized by the expression of cytokeratins 5 and
      14, whereas the secretory luminal cells contain cytokeratins 8 and 18. Cells
      cultured from the prostatic epithelium expressed cytokeratins 5, 8, and 18, and
      thus had features of both basal and luminal cells. Certain growth-inhibitory
      conditions altered keratin expression in conjunction with growth modulation.
      Deletion of peptide factors and hormones from the culture medium induced the
      expression of cytokeratins 1 and 10, associated with a squamous phenotype. These
      same squamous keratins were found in very dense, stratified cultures that were
      maintained at confluency in standard, complete medium for extended periods.
      Retinoic acid enhanced the expression of secretory luminal cell-associated
      cytokeratins 8 and 18 in semi-confluent cultures. Other growth inhibitory factors
      such as suramin, transforming growth factor-beta, and interferon-gamma had no
      effect on keratin expression. These observations indicate that the
      differentiation of prostatic epithelial cells can be directed toward alternate
      pathways, either squamous or secretory, by different growth-inhibitory
      conditions. However, not all growth inhibitory factors altered differentiation,
      demonstrating that growth inhibition in itself is not a sufficient inducer of
      differentiation.

PMID- 7519970
TI  - Nitric oxide synthase in the enteric nervous system of the guinea-pig: a
      quantitative description.
AB  - The distribution and abundance of nitric oxide synthase (NOS)-containing neurons
      and their terminals in the gastrointestinal tract of the guinea-pig were examined
      in detail using NADPH diaphorase histochemistry and NOS immunohistochemistry. NOS
      containing cell bodies were found in the myenteric plexus throughout the
      gastrointestinal tract and in the submucous plexus of the stomach, colon and
      rectum. NOS-containing neurons comprised between 12% (in the duodenum) and 54%
      (in the esophagus) of total myenteric neurons. In the ileum, NOS neurons
      represented 19% of total myenteric neurons. Most of the NOS neurons throughout
      the gastrointestinal tract possessed lamellar dendrites and a single axon. NOS
      containing terminals were abundant in the circular muscle, including that of the
      sphincters, but were rare in the longitudinal muscle, except for the taeniae of
      the caecum. The muscularis mucosae of the esophagus, stomach, colon and rectum
      received a medium to dense innervation by NOS terminals. Within myenteric
      ganglia, NOS-containing terminals were extremely sparse in the esophagus, stomach
      and duodenum, common in the ileum and distal colon and extremely dense in the
      proximal colon and rectum. The submucous plexus in the ileum and large intestine
      contained a sparse plexus of NOS-containing terminals. NOS terminals were not
      observed in the mucosa of any region. We conclude that throughout the
      gastrointestinal tract of the guinea-pig, NOS neurons are inhibitory motor
      neurons to the circular muscle; in the ileum and large intestine, NOS neurons may
      also function as interneurons.

PMID- 7519973
TI  - Studies on the binding and transcriptional properties of aflatoxin B1-8,9
      epoxide.
AB  - [3H]Aflatoxin B1-8,9-epoxide ([3H]AFB1-8,9-epoxide), the putative ultimate
      carcinogen of AFB1, was synthesized and tested for its binding specificity to and
      transcriptional effect on several single- and double-stranded DNAs containing
      cytosine. The test was carried out over a 200-fold concentration range (i.e. 0.1
      20 microgram [3H]AFB1-8,9-epoxide per 0.025 A260 units of DNA). The results show:
      (i) [3H]AFB1-8,9-epoxide bound preferentially to the double-stranded alternating
      co-polymer poly[d(G-C)] over the double-stranded poly(dG).poly(dC) and single
      stranded poly(dG) or poly(dC) homopolymers. (ii) The binding affinity of [3H]AFB1
      8,9-epoxide to poly(dC) was essentially the same as the poly(dG). (iii) Under
      identical conditions, [3H]AFB1-8,9-epoxide bound to poly(dG).poly(dC) 2.5-3 times
      more than to poly[d(I-C)]; however, poly[d(I-C)]-directed RNA synthesis was
      clearly more sensitive to [3H]AFB1-8,9-epoxide inhibition than poly(dG).poly(dC).
      Conversely, the binding affinity of [3H]AFB1-8,9-epoxide to poly(dC) and to
      poly[d(I-C)] was quite similar, yet poly(dC)-directed RNA synthesis was much more
      resistant to [3H]AFB1-8,9-epoxide inhibition than poly[d(I-C)]. (iv) After
      [3H]AFB1-8,9-epoxide was hydrolyzed to [3H]AFB1-8,9-dihydrodiol (0.01 N NaOH, 10
      min 23 degrees C), it was no longer able to bind poly[d(G-C)] or to inhibit
      poly[d(G-C)]-directed RNA synthesis. These results confirm our earlier studies
      using microsome-activated AFB1 and AFB1-Cl2 that AFB1 after activation is able to
      bind cytosine in DNA, and the binding is not via AFB1-8,9-dihydrodiol.
      Furthermore, the results also suggest that AFB1 adducts may not have the same
      biological effect depending on the base, sequence as well as the conformation of
      the DNA where the adducts are formed.

PMID- 7519971
TI  - Neurons projecting from the brain to the corpora allata in orthopteroid insects:
      anatomy and physiology.
AB  - Retrograde and orthograde labeling of neurons projecting to the corpus allatum
      was performed in locust, grasshopper, cricket, and cockroach species in order to
      identify brain neurons that may be involved in the regulation of juvenile hormone
      production. In the acridid grasshopper Gomphocerus rufus L., and the locusts
      Locusta migratoria (R.&F.) and Schistocerca gregaria Forskal, the corpora allata
      are innervated by two morphologically distinguishable types of brain neurons. One
      group of 9-13 neurons (depending on species) with somata in the pars lateralis
      extend axons via the nervus corporis cardiaci 2 and nervus corporis allati 1 to
      the ipsilateral corpus allatum, whereas two cells in each pars lateralis have
      bilateral projections and innervate both glands. No direct connection between the
      pars intercerebralis and corpus allatum has been found. In contrast, neurons with
      paired axons innervating both glands are not present in Periplaneta americana
      (L.) and Gryllus bimaculatus de Geer. Instead, two cells in each pars lateralis
      project only to the gland contralateral to their somata. Electrophysiological
      experiments on acridid grasshoppers have confirmed the existence of a direct
      conduction pathway between the two glands via the paired axons of four cells that
      have been identified by neuroanatomy. These cells are not spontaneously active
      under experimental conditions. Ongoing discharges in the left and right nerves
      are unrelated, suggesting that the corpora allata receive independent neuronal
      inputs from the brain.

PMID- 7519972
TI  - Differential effects of procarbazine and methylnitrosourea on the accumulation of
      O6-methylguanine and the depletion and recovery of O6-alkylguanine-DNA
      alkyltransferase in rat tissues.
AB  - The kinetics of accumulation of the premutagenic DNA adduct O6-methylguanine (O6
      meG) in the liver, blood leukocytes, lymph nodes and bone marrow of rats was
      examined and compared after single or multiple doses of procarbazine, a
      methylating cytostatic drug employed in the treatment of Hodgkin's lymphoma
      patients, and methylnitrosourea (MNU), an experimental methylating agent and
      carcinogen. Maximal O6-meG levels occurred 1-2 h after administration of single
      doses of procarbazine (10 mg/kg) or MNU (1 mg/kg), thereafter decreasing with
      half-lives of approximately 20-45 h, depending on the tissue. A relatively
      uniform tissue distribution was observed with both agents, with the liver
      generally showing highest adduct levels, followed by the lymph nodes, bone marrow
      and blood leukocytes which contained broadly similar amounts of O6-meG. During
      daily, oral administration to rats of procarbazine for 10 days at dose rates of
      2.5, 5, 10 or 20 mg/kg/day (treatment analogous to that of the MOOP chemotherapy
      protocol for Hodgkin's lymphoma) followed by animal death on different days (in
      each case 24 h after the last treatment), a biphasic mode of O6-meG induction was
      observed: an initially steep build-up during the first 3-4 days was followed by a
      transient decline in the rate of accumulation, in turn followed by a second wave
      of accumulation and then a further slow-down. During the same treatment, liver O6
      methylguanine-DNA alkyltransferase (AGT) declined in a dose-related manner. AGT
      recovery after the end of treatment was slow, taking nearly 20 days after the end
      of the high-dose treatment to return to control levels, despite the fact that all
      detectable adducts had been lost from DNA within 3 days after the end of
      treatment. A similar depletion and slow recovery of AGT in the liver, blood
      lymphocytes, bone marrow and lymph nodes was observed after treatment with a
      single dose of 100 mg/kg procarbazine. In contrast to these observations, O6-meG
      accumulated smoothly during a 10 day administration of MNU (1 or 10 mg/kg/day) to
      reach a steady-state within 5-6 days, while liver AGT was partially depleted
      after the high dose and recovered fully within 72 h of cessation of treatment.
      Similarly, a single dose of MNU (35 mg/kg) resulted in AGT depletion followed by
      rapid recovery in all four tissues examined. It is concluded that procarbazine
      (but not MNU) causes a decrease in cellular AGT concentrations by a mechanism
      additional to suicide repair of O6-meG.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7519975
TI  - Localization of colonic lesions with endoscopic tattoo.
AB  - PURPOSE: Intraoperative localization of small tumors or polypectomy sites is
      frequently a difficult problem. In addition, the distance measured from the anus
      to the lesion by the endoscopist can be inaccurate. The purpose of our study was
      to evaluate the utility of India ink tattoo injection as a preoperative marking
      technique before colon surgery. METHODS: Colonic lesions were marked at
      preoperative colonoscopy, by multiple, small-volume injections of sterile India
      ink using a sclerotherapy needle, adjacent to the lesion. RESULTS: This technique
      was used in 14 patients with colonic carcinoma or villous adenoma not amenable to
      polypectomy. There was excellent intraoperative localization of the lesion in 11
      patients. The complication rate was 7 percent. CONCLUSION: Colon tattoo allows
      precise localization of lesions with minimal risk at the time of resection.

PMID- 7519974
TI  - Generation and characterization of novel antibodies highly selective for
      phosphorylated linker histone H1 in Tetrahymena and HeLa cells.
AB  - Phosphorylated forms of Tetrahymena macronuclear histone H1 were separated from
      each other and from dephosphorylated H1 by cation-exchange HPLC. A homogeneous
      fraction of hyperphosphorylated macronuclear H1 was then used to generate novel
      polyclonal antibodies highly selective for phosphorylated H1 in Tetrahymena and
      in human cells. These antibodies fail to recognize dephosphorylated forms of H1
      in both organisms and are not reactive with most other nuclear or cytoplasmic
      phosphoproteins including those induced during mitosis. The selectivity of these
      antibodies for phosphorylated forms of H1 in Tetrahymena and in HeLa argues
      strongly that these antibodies recognize highly conserved phosphorylated epitopes
      found in most H1s and from this standpoint Tetrahymena H1 is not atypical. Using
      these antibodies in indirect immunofluorescence analyses, we find that a
      significant fraction of interphase mammalian cells display a strikingly punctate
      pattern of nuclear fluorescence. As cells enter S-phase, nuclear staining becomes
      more diffuse, increases significantly, and continues to increase as cells enter
      mitosis. As cells exit from mitosis, staining with the anti-phosphorylated H1
      antibodies is rapidly lost presumably owing to the dephosphorylation of H1. These
      immunofluorescent data document precisely the cell cycle changes in the level of
      H1 phosphorylation determined by earlier biochemical studies and suggest that
      these antibodies represent a powerful new tool to probe the function(s) of H1
      phosphorylation in a wide variety of eukaryotic systems.

PMID- 7519978
TI  - Fine needle aspiration cytology combined with argyrophilic nucleolar organizer
      regions (AgNORs) in diagnosis of thyroid neoplasms.
AB  - NORs are the loops of DNA that contain the sites of ribosomal genes around which
      the nucleolus is formed during telophase of mitosis. In light microscopy they can
      be visualized by simple silver staining technique as small dark dots within the
      nucleus. It has been recognized that in many neoplasms, especially malignant
      AgNORs are more numerous and often atypical when compared with benign tumors and
      normal tissue. We have introduced this novel technique to the fine needle
      cytology of thyroid neoplasms (n = 56). We have analyzed the number, the area of
      AgNORs, the number of clustered AgNORs in the nucleus and the ratio of AgNOR area
      to the nuclear area and the area of single AgNOR by means of semiautomatic
      computerized image analysis. We have studied cytological samples consisting of 7
      simple goiters, 7 hyperplasias, 15 follicular adenomas, 7 oxyphilic follicular
      adenomas, 6 follicular carcinomas, 8 oxyphilic follicular carcinomas, 6 papillary
      adenocarcinomas. In this study we have demonstrated that some differences in the
      AgNORs value are associated with the type of tumor rather than with malignancy.
      Location of the AgNORs seems to be very typical for some types of tumors. For
      example in oxyphilic neoplasms they form single clusters in the nucleus and in
      papillary adenocarcinomas they form at least two abundant clusters. In other
      proliferative lesions of the thyroid gland location of AgNORs is less typical.

PMID- 7519977
TI  - Buprenorphine: duration of blockade of effects of intramuscular hydromorphone.
AB  - Six opioid-dependent in-patients were maintained on daily sublingual doses of
      buprenorphine at 2, 6, and 12 mg/day for five days at each dose in a randomized,
      balanced sequence. Placebo buprenorphine was substituted for the next three days,
      and challenge doses of the mu agonist hydromorphone were administered on the
      three days. Planned comparisons in a 3-factor ANOVA showed dose-dependent
      hydromorphone effects, significant blockade of 'high' by the 12 mg buprenorphine
      dose, and no differences on hydromorphone-induced 'high' across 72 h of active
      buprenorphine. The data suggest that the blockade by buprenorphine of 'high'
      persists for at least 72 h after the last dose of buprenorphine.

PMID- 7519976
TI  - 12-lead and continuous ECG recordings of subjects during inpatient administration
      of smoked cocaine.
AB  - Cocaine can cause myocardial ischemia or infarction. The incidence of these
      events, and the influence of specific dosing routes or regimens on their
      occurrence is not established. In the current study, we obtained frequent 12-lead
      electrocardiograms (ECGs) and continuous 2 or 3 channel ECGs from 20 subjects
      participating in a behavioral study of smoked cocaine. Subjects received 10 or 11
      doses of cocaine 0.4 mg/kg per dose, or 10 doses of 35 mg per dose at 30 min
      intervals (range 233-408 mg total dose per session). ECGs were also recorded on
      control days on which subjects received no cocaine. The mean peak plasma cocaine
      concentration on cocaine days was 640 +/- 262 ng/ml. There were no changes in
      digitized ST segment amplitude on 12-lead ECGs obtained during cocaine
      administration (P = 0.098). Of 17 subjects who had technically satisfactory
      continuous ECGs, four had significant ST segment depression (> 1 mm below the PR
      segment); two on cocaine days and two on control days (P > 0.5). One subject had
      frequent premature beats on both cocaine and control days. One subject had an
      asymptomatic run of 4 ventricular beats 30 s after cocaine administration that
      could have been due to cocaine. All episodes of ST depression or premature beats
      were asymptomatic. No evidence of either symptomatic or subclinical cardiac
      ischemia related to cocaine administration was found. Thus no clinically
      important adverse events were found as a result of smoked cocaine administered by
      this dosing regimen to healthy males with a history of heavy cocaine use.
      Additional study with larger numbers of subjects will be helpful in further
      assessing the safety of administering smoked cocaine to research subjects.

PMID- 7519979
TI  - Effect of the combined administration of galanin and clonidine on serum growth
      hormone levels in normal subjects and in patients under chronic glucocorticoid
      treatment.
AB  - Aim of our study was to investigate the effect of clonidine and galanin (alone or
      in combination) on growth hormone (GH) secretion in normal subjects and in adult
      patients with increased somatostatin tone due to chronic daily immunosuppressive
      glucocorticoid treatment. We studied 7 adult patients undergoing long-term (no
      less than 6 months) immunosuppressive glucocorticoid treatment for non endocrine
      diseases (4F, 3M; age 49.7 +/- 6.3 years). Six normal adult nonobese subjects
      (3F, 3M; age 34 +/- 2.7 years) served as controls. All subjects underwent the
      following three tests in random order: 1) iv infusion of clonidine, 150
      micrograms in 10 mL of saline, from time 0 to 10 min; 2) iv infusion of synthetic
      porcine galanin, 500 micrograms in 100 mL of saline from -15 to 30 min; 3) iv
      infusion of clonidine from 0 to 10 min combined with synthetic porcine galanin iv
      infusion from -15 to 30 min. Blood samples for GH assay were taken at -15, 0, 15,
      30, 45, 60, 90, 120 min. No significant differences in GH absolute values were
      observed at any time between the three different tests within each group of
      subjects. Normal subjects showed significantly (p < 0.05) higher GH peaks and GH
      absolute values from 15 to 90 min after galanin alone, clonidine alone and
      clonidine+galanin with respect to the glucocorticoid-treated patients. The
      absence of any either synergistic or at least additive effect on GH secretion of
      galanin and clonidine in conditions of both normal and increased somatostatin
      tone suggests that also in man, as well as in the rat, the action of galanin on
      the GH axis may be mediated through alpha-adrenergic pathways.

PMID- 7519980
TI  - Purification and identification of tyrosine-phosphorylated proteins from B
      lymphocytes stimulated through the antigen receptor.
AB  - The activation of protein tyrosine kinase (PTKs) and subsequent tyrosine
      phosphorylation of cellular proteins is a critical initial signal in the response
      of eukaryotic cells to mitogens, differentiative signals, and other stimuli. A
      number of PTK substrates have been identified and many of these are components of
      signal transduction pathways that regulate cell function. However, the majority
      of proteins that are tyrosine-phosphorylated in response to receptor signaling
      remain unidentified. As some of these unidentified PTK substrates may also be
      signal-transducing proteins, their identification and functional characterization
      is an important objective towards understanding receptor signaling. We describe
      the development of a comprehensive and general process for the isolation and
      structural characterization of tyrosine-phosphorylated proteins. The method
      involves enrichment by anti-phosphotyrosine affinity chromatography,
      electrophoretic concentration and separation, and proteolytic fragmentation of
      individual purified phosphoproteins. Resulting peptide fragments are separated by
      microbore reverse-phase high performance liquid chromatography (RP-HPLC) and a
      portion of the eluted peptides are subjected to electrospray-mass spectrometry
      (ES/MS) for accurate determination of peptide masses. Proteolytic fragmentation
      of a protein produces a characteristic set of peptide masses that can be used to
      rapidly identify the protein by searching databases containing the peptide mass
      "fingerprints" for all known proteins. The identity of the protein established by
      this method can be confirmed by sequence analysis of selected peptides. We have
      applied this procedure to the analysis of PTK substrates from B lymphocytes that
      have been stimulated through the B cell antigen receptor (BCR). Signaling by this
      receptor is involved in the generation of antibodies against foreign molecules
      (antigens). The BCR activates multiple PTKs which phosphorylate at least 30
      different proteins. We have identified several of these tyrosine-phosphorylated
      proteins, including Syk, a PTK that is known to be tyrosine-phosphorylated in
      activated B cells. Thus, the procedure described here can be used to identify
      regulatory proteins of low abundance. The process consists of a logical
      succession of compatible steps that avoids pitfalls inherent to prior attempts to
      characterize low abundance phosphoproteins and should find wide use for the
      identification of tyrosine-phosphorylated proteins in other cell types.

PMID- 7519981
TI  - Hemoglobin function under extreme life conditions.
AB  - Considering the variety of species that depend on hemoglobin for oxygen
      transport, these molecules must execute their primary function under extreme
      environmental conditions. Hence, a thermodynamic analysis of oxygen binding with
      hemoglobins from different species reveals a series of adaptive mechanisms which
      are based on the thermodynamic connection between the binding of heterotropic
      effectors and the reaction with oxygen. The examples reported, from fishes to
      human fetus, illustrate how evolution can alter the structural basis of the
      heterotropic interactions to optimize the oxygenation-deoxygenation cycle in
      dependence of the physiological needs of the particular organisms. Moreover they
      show that a thermodynamic analysis of the reaction with oxygen overcomes the
      meaning of a detailed structural and functional characterization going deeper
      into the physiology of the specific organism.

PMID- 7519983
TI  - Differential inhibitory effects of GMP-2',3'-dialdehyde on human and schistosomal
      hypoxanthine-guanine phosphoribosyltransferases.
AB  - The hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) of human and the
      parasitic trematode, Schistosoma mansoni, were expressed at high levels in
      transformed Escherichia coli in their native forms. Guanosine 2',3'-dialdehyde 5'
      phosphate (ox-GMP) was shown to bind irreversibly to both enzymes in a time
      dependent manner. This binding was stabilized by sodium borohydride reduction,
      suggesting that a Schiff's base is formed between the dialdehyde groups of ox-GMP
      and the amino group of a lysine residue in the enzymes. This linkage formation
      applies also to inosine 2',3'-dialdehyde 5'-phosphate but not to adenosine 2',3'
      dialdehyde 5'-phosphate. GMP was found to be protective against ox-GMP
      inactivation and [3H]ox-GMP labeling of both HGPRTases. 5-Phosphoribosyl-1
      diphosphate (PRibPP) also protects human HGPRTase against the ox-GMP inactivation
      and [3H]ox-GMP labeling but provides virtually no protection against the ox-GMP
      inactivation and labeling of the schistosomal enzyme, even though PRibPP binds to
      the latter with a threefold higher affinity. These results imply that PRibPP and
      ox-GMP compete with each other for binding to the human HGPRTase but not for
      binding to the schistosomal enzyme. This discrepancy could be exploited for the
      purpose of designing selective inhibitors of the schistosomal HGPRTase. Guanosine
      2',3'-dialdehyde (ox-guanosine) is nearly as active as ox-GMP in inhibiting
      schistosomal HGPRTase but much less potent in inhibiting human HGPRTase,
      suggesting that ox-guanosine and ox-GMP may bind equally well to the parasite
      enzyme. PRibPP can protect human but not schistosomal HGPRTase against the
      inactivation by ox-guanosine. Therefore, ox-GMP and ox-guanosine must be forming
      Schiff's bases with the same amino acid residues in each of the two HGPRTases.

PMID- 7519982
TI  - The ribosomal protein S8 from Thermus thermophilus VK1. Sequencing of the gene,
      overexpression of the protein in Escherichia coli and interaction with rRNA.
AB  - The gene of the ribosomal protein S8 from Thermus thermophilus VK1 has been
      isolated from a genomic library by hybridization of an oligonucleotide coding for
      the N-terminal amino acid sequence of the protein, amplified by PCR and
      sequenced. Nucleotide sequence reveals an open reading frame coding for a protein
      of 138 amino acid residues (M(r) 15,839). The codon usage shows that 94% of the
      codons possess G or C in the third position, and agrees with the preferential
      usage of codons of high G+C content in the bacteria of the genus Thermus. The
      amino acid sequence of the protein shows 48% identity with the protein from
      Escherichia coli. Ribosomal protein S8 from T. thermophilus has been expressed in
      E. coli under the control of the T7 promoter and purified to homogeneity by heat
      treatment of the extract followed by cation-exchange chromatography. Conditions
      were defined in which T. thermophilus protein S8 binds specifically an homologous
      16S rRNA fragment containing the putative S8 binding site with an apparent
      association constant of 5 x 10(7) M-1. The overexpressed protein binds the rRNA
      with the same affinity as that extracted from T. thermophilus, indicating that
      the thermophilic protein is correctly folded in E. coli. The specificity of this
      binding is dependent on the ionic strength. The protein S8 from T. thermophilus
      recognizes the E. coli rRNA binding sites as efficiently as the S8 protein from
      E. coli. This result agrees with sequence comparisons of the S8 binding site on
      the small subunit rRNA from E. coli and from T. thermophilus, showing strong
      similarities in the regions involved in the interaction. It suggests that the
      structural features responsible for the recognition are conserved in the
      mesophilic and thermophilic eubacteria, despite structural peculiarities in the
      thermophilic partners conferring thermostability.

PMID- 7519984
TI  - The stabilizing effects of hydrophobic cores on peptide folding of bovine
      pancreatic-trypsin-inhibitor folding-intermediate model.
AB  - A synthetic peptide model composed of alpha-helical and beta-sheet portions (P
      alpha P beta) is a crucial folding intermediate in the folding of bovine
      pancreatic trypsin inhibitor (BPTI), which contains 30 amino acid residues, and
      provides a good model for studying the folding structure. Using this model the
      roles of hydrophobic cores, such as non-polar amino acids and a short beta
      strand, in the folding structure stability were investigated by deleting the
      hydrophobic amino acids or substituting with Ala. As a first step, a mutant
      peptide, P alpha 6 P beta 1, was made by removing the four residues (NNFK46) from
      the N-terminus of P alpha which make a short beta strand in native BPTI, and each
      of the hydrophobic cores, Phe45 of P alpha and Tyr21 of P beta, were substituted
      by Ala. Without the short beta strand the peptide still folds in spite of its low
      solubility, suggesting that a simple alpha helix and central antiparallel beta
      sheet contain sufficient information to direct the folding of this region of
      molecule. The peptide without Tyr21 was much more unstable than P alpha 6 P beta
      1, such that most of the folding structure collapsed even at 0 degree C, whereas
      without Phe45 the structure was more stable than P alpha 6 P beta 1. This
      indicates that the hydrophobic interactions of Tyr21 in P beta are more important
      in BPTI folding.

PMID- 7519985
TI  - Ligand-binding properties and N-glycosylation of alpha 1 subunit of the alpha
      amino-3-hydroxy-5-methyl-4-isoxazole-propionate(AMPA)-selective glutamate
      receptor channel expressed in a baculovirus system.
AB  - The alpha 1 subunit of the mouse alpha-amino-3-hydroxy-5-methyl-4-isoxazole-
      propionate(AMPA)-selective glutamate receptor channel has been expressed in
      insect Spodoptera frugiperda cells using a baculovirus system. The recombinant
      receptor proteins were identified by immunocytochemical detection, Western-blot
      analysis, and [35S]methionine/[35S]cysteine metabolic labeling experiments. The
      effect of tunicamycin on the metabolic labeling and immunoblots suggested that
      the two products, a major protein species of approximately 104 kDa and a minor
      species of approximately 100 kDa, correspond to glycosylated and non-N
      glycosylated forms, respectively, which was also supported by the enzymic
      deglycosylation experiments. The lack of alpha-amino-3-hydroxy-5-methyl-4
      isoxazole-propionate-binding activity of non-N-glycosylated glutamate receptor
      expressed in the presence of tunicamycin suggested that N-glycosylation is
      required, directly or indirectly, for functional expression in insect cells for
      ligand binding. Scatchard analysis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate binding showed a single binding site with Kd 30 nM and a Bmax value of
      2.6 x 10(5) binding sites/cell or 1.5 pmol/mg protein in the total particulate
      fraction. Among the compounds tested in the competition studies, beta-(3,5-dioxo
      1,2,4-oxadiazolidin-2-yl)-L-alanine (quisqualate) was the most potent inhibitor
      of the 3H-labeled alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate binding
      (IC50 = 30 nM), followed in decreasing order by alpha-amino-3-hydroxy-5- methyl-4
      isoxazole propionate, L-glutamate, 6,7-dinitroquinoxaline-2,3-dione, 6-cyano-7
      nitroquinoxaline-2,3-dione, and 2-carboxy-4-(1-methylethenyl)-3
      pyrrolidineacetate (kainate). Thus, in this study we present detailed analysis of
      alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionate-binding activity of the
      homomeric (single subunit) glutamate receptor channel of mouse alpha 1 subunit
      and discuss possible roles of N-glycosylation of the glutamate receptor channel
      alpha 1 subunit.

PMID- 7519986
TI  - Identification of the dihydrolipoamide acetyltransferase subunit of the human
      pyruvate dehydrogenase complex as an autoantigen in halothane hepatitis.
      Molecular mimicry of trifluoroacetyl-lysine by lipoic acid.
AB  - Trifluoroacetylated (CF3CO-) proteins, elicited upon exposure of animals or
      humans to halothane, were recognized by anti-CF3CO antibody, monospecific for the
      hapten derivative N6-trifluoroacetyl-L-lysine. Anti-CF3CO antibodies cross
      reacted with the dihydrolipoamide acetyltransferase (E2 subunit) of pyruvate
      dehydrogenase, indicating that epitopes on the E2 subunit of pyruvate
      dehydrogenase molecularly mimic those on CF3CO-proteins. Lipoic acid, the
      prosthetic group of the E2 subunit of pyruvate dehydrogenase was essential in
      this process, in that only the lipoylated form of the recombinantly expressed
      inner lipoyl domain of the human E2 subunit of pyruvate dehydrogenase, but not
      the unlipolyated form, was recognized by anti-CF3CO antibody. Furthermore, based
      on a high degree of structural relatedness, both CF3CO-Lys and (6RS)-lipoic acid,
      as well as the lipoylated peptide ETDK(lipoyl)ATIG specifically inhibited the
      recognition by anti-CF3CO antibody of the E2 subunit of pyruvate dehydrogenase,
      of trifluoroacetylated rabbit serum albumin and of human liver CF3CO-proteins. In
      sera of patients with halothane hepatitis, autoantibodies with properties
      identical to those of anti-CF3CO antibody were identified which could not
      discriminate between CF3CO-proteins and the E2 subunit of pyruvate dehydrogenase.
      These data suggest that the E2 subunit pyruvate of dehydrogenase is an
      autoantigen in halothane hepatitis and that molecular mimicry of CF3CO-proteins
      by the E2 subunit of pyruvate dehydrogenase is due to the similar structures of
      CF3CO-Lys and lipoic acid.

PMID- 7519987
TI  - Cloning and structural characterization of the human endothelial nitric-oxide
      synthase gene.
AB  - Nitric oxide accounts for the activity of endothelium-derived relaxing factor,
      which seems to have an important role in vasodilation and inhibition of platelet
      aggregation. In endothelial cells, one isoform of nitric-oxide synthase is
      constitutively expressed. Analysis of the cDNA encoding the human endothelial
      nitric-oxide synthase revealed that the mRNA is 4.1 kb in size and that the
      translated protein consists of 1203 amino acids. We have cloned a genomic DNA
      encoding the human endothelial nitric-oxide synthase and analyzed the entire
      nucleotide sequence of the gene. The gene consists of 26 exons with a total size
      of 21 kb. The 5' flanking region of the gene lacks TATA boxes, but it contains
      putative Sp1-binding sites in (G+C)-rich regions. Of particular interest is the
      fact that a shear-stress-responsive element is located at position -985, which
      probably regulates the nitric-oxide-synthase gene in response to fluid mechanical
      forces at the transcriptional level in the vascular endothelium. Two
      minisatellite sequences are detectable in introns 2 and 8; a 32-bp consensus
      sequence repeats 38 times and a 57-bp consensus sequence repeats ten times. We
      found polymorphisms of the BamHI fragment containing the former minisatellite
      sequence in genomic DNA from pedigree family members. Furthermore, five tandem
      repeats of a 27-bp core consensus sequence and 35 repeats of a dinucleotide (CA)
      are located in introns 4 and 13, respectively. These repeat sequences will
      probably provide genetic markers for gene mapping and linkage analysis of
      inherited diseases including cardiovascular diseases.

PMID- 7519988
TI  - Denaturation of free and complexed bovine trypsinogen with the calcium ion,
      dipeptide Ile-Val and basic pancreatic trypsin inhibitor (Kunitz).
AB  - Thermal and chemical denaturation has been used to probe changes in the
      thermodynamic stability of trypsinogen upon complexation with calcium ion and
      with ligands, which induce the conformational transition of the zymogen to the
      trypsin-like form. Chemical and thermal unfolding curves of ligand-free
      trypsinogen at pH 5.8 are cooperative and yielded the following stability
      parameters: the free energy change of denaturation delta Gden = 44.8 kJ/mol, the
      denaturation temperature = 65.7 degrees C, the enthalpy change of denaturation
      delta Hden at the denaturation temperature Tden = 607 kJ/mol and the heat
      capacity change of denaturation delta Cp,den = 12.4 kJ.mol-1.K-1. Fast phases of
      both unfolding and refolding of trypsinogen proceed on a time scale of seconds
      and fit to a single exponential. At pH 5.8, the calcium ion increases the
      conformational stability delta Gden by 7.1 kJ/mol, Tden by 2.6 K and delta Hden
      by 80 kJ/mol, but does not induce any substantial structural change in the
      trypsinogen molecule, as revealed by 1H-NMR spectra. The trypsin-like form of
      trypsinogen, generated by complexation of the zymogen with the dipeptide Ile-Val
      and/or basic pancreatic trypsin inhibitor (Kunitz), is characterized by increase
      of delta Hden by 134 kJ/mol and Tden by 2.5 K, which may be attributed to the
      additional energy required to disrupt the rigidified activation domain in the
      complexed trypsinogen.

PMID- 7519989
TI  - Serum prostate-specific antigen discriminates weakly between men with benign
      prostatic hyperplasia and patients with organ-confined prostate cancer.
AB  - To determine if serum prostate-specific antigen (PSA) can identify those patients
      harboring an organ-confined prostate cancer prior to treatment for symptomatic
      benign prostatic hyperplasia (BPH), we examined retrospectively the preoperative
      serum PSA level for two groups of men. Group 1 consisted of 187 consecutive
      patients with a histologic diagnosis of BPH as determined from complete
      pathologic analysis of the transurethral resection of the prostate (TURP)
      specimen. Group 2 included 198 consecutive patients with histologically confirmed
      organ-confined prostate cancer as determined from step-section analysis of the
      retropubic radical prostatectomy specimen. The median serum PSA value for group 1
      was 3.9 ng/ml (range 0.2-55 ng/ml), whereas the median serum PSA level for group
      2 was 5.9 ng/ml (range 0.4-58 ng/ml). Although this difference was statistically
      significant (p < 0.001), the distribution of serum PSA values for group 1
      overlapped considerably with the distribution for group 2. For both groups, there
      was a clustering of PSA values below 10.0 ng/ml (group 1: 90%; group 2: 73%). The
      area under the receiver operating characteristic curve for log PSA values to
      discriminate men with BPH from patients with organ-confined prostate cancer was
      0.66 (95% confidence interval: 0.60-0.72); a 'perfect' test has an area of 1.0,
      whereas a test with 'no information value' has an area of 0.5. These findings
      suggest that serum PSA has only a modest ability to distinguish men with BPH from
      patients with organ-confined prostate cancer. As a result, some symptomatic BPH
      patients choosing a non-TURP therapy may harbor a clinically significant prostate
      cancer despite being evaluated with a serum PSA determination.

PMID- 7519990
TI  - Prostate-specific antigen density: a means to enhance detection of prostate
      cancer.
AB  - The ability of serum prostate-specific antigen (PSA) and PSA density (PSAD) to
      distinguish patients with prostate cancer from those with benign diseases of the
      prostate was assessed in 495 men. All men were evaluated with PSA determination,
      digital rectal examination (DRE), transrectal ultrasonography (TRUS) and
      ultrasound-guided prostatic biopsies. PSA was analysed by the polyclonal (Yang)
      assay. Prostate volume was estimated from TRUS. PSAD was determined by dividing
      the serum PSA by the volume of the prostate. Prostatic biopsies identified cancer
      in 246 of the 495 patients (49.7%). The entire group was divided into 6 subgroups
      according to PSA level at presentation. Cancer and noncancer patients were
      compared in each subgroup with respect to the values of PSA, prostate volume and
      PSAD. For the entire group of patients, there was no statistically significant
      advantage, for PSAD over serum PSA alone, in distinguishing between benign and
      malignant prostatic conditions. However, when patients were stratified according
      to PSA level, PSAD was statistically significantly superior to serum PSA alone in
      the detection of prostate cancer for PSA values in the intermediate range (2.6-30
      ng/ml). This analysis with respect to the DRE and TRUS results showed PSAD to be
      superior to PSA when both examinations are normal. Our results demonstrate that
      the influence of PSAD level on cancer detection proportionally increases as the
      PSAD value increases. Curves constructed from the incidence of prostate cancer
      according to PSAD values may be useful to select patients with intermediate
      levels of serum PSA, and normal DRE and TRUS for prostatic biopsies.

PMID- 7519991
TI  - Differentiation of benign prostatic hyperplasia and prostate cancer employing
      prostatic-specific antigen density.
AB  - To enhance the ability of prostate-specific antigen (PSA) to distinguish benign
      prostatic hyperplasia (BPH) from cancer of the prostate (CaP) Benson et al.
      defined a new parameter, PSA density (PSAD), which is the ratio of the serum PSA
      concentration to the volume of the prostate. We have employed this parameter in a
      prospective study of 28 patients with clinically localised CaP and 57 patients
      with BPH. Mean PSAD was 0.116 for the BPH patients and 0.46 for the CaP patients
      (p < 0.005). The authors conclude that the information provided by PSAD is
      superior to absolute PSA values in the differentiation between BPH and CaP.

PMID- 7519992
TI  - Impact of prostate-specific antigen density in benign prostatic hyperplasia and
      prostate carcinoma. Preliminary results.
AB  - In an attempt to enhance the success of prostate-specific antigen (PSA) in the
      diagnosis and staging of prostate carcinoma (PCa) the concept of PSA density
      (PSAD) has been introduced by Benson et al. Likewise a study to investigate the
      role of PSAD in 53 patients with PCa and 47 patients with benign prostatic
      hyperplasia (BPH) has been done. PSADs seemed to increase directly proportional
      to the grade in PCa and differed significantly between patient groups with BPH
      and localized+metastatic PCa, BPH and localized PCa, and localized PCa and
      metastatic PCa. Although 0.6 level for PSAD seemed to be a rational cut-off level
      in our study, this issue needs to be studied in multiple centers involving an
      increased number of patients for resolution.

PMID- 7519993
TI  - Anchored polymerase chain reaction based analysis of the V beta repertoire in the
      non-obese diabetic (NOD) mouse.
AB  - We have performed extensive analyses of T cell receptor V beta usage in the
      thymus, the spleen and the infiltrated islets of preclinical non-obese diabetic
      (NOD) mice. A semiquantitative anchored polymerase chain reaction (An-PCR)
      protocol has been developed for this purpose. The validity of the method has been
      first assessed by antibody staining with a panel of anti-V beta monoclonal
      antibodies (mAb). The results obtained by An-PCR are accurate, reproducible, and
      in good agreement with cell surface protein staining. A strict comparison between
      thymus and spleen repertoires reveals no major V beta-specific deletion except
      the already reported V beta 3 deletion due to Mtv-3. Certain V beta such as V
      beta 15, 18, 20 are found with a low frequency in the spleen, but the fact that
      they are also scarce in the thymus probably reflects a poor availability of these
      genetic elements during beta chain rearrangement rather than negative selection.
      Other V beta, such as V beta 2, V beta 12 and V beta 14 are significantly more
      abundant in the spleen than in the thymus. This finding was confirmed by mAb
      staining for V beta 2 and V beta 14. The expansion asymmetrically affects the
      CD4+ subset and can be traced back to the mature, single-positive thymocyte
      subset, suggesting an intrathymic positive selection event. V beta repertoires in
      infiltrated islets of 13- and 18-week-old, non-diabetic mice are polymorphic.
      Practically all the V beta found in the peripheral lymphoid tissues are present
      in the islets, in similar proportions. The major exception is V beta 12, one of
      the V beta which is subject to expansion during intrathymic differentiation and
      which is further augmented in the islets, both at 13 and 18 weeks. This increase
      probably reflects further peripheral amplification of the V beta 12-bearing
      subset due to encounter with the same ligand as in the thymus or with a cross
      reactive motif. Finally, the nucleotide sequencing of all the V beta segments in
      usage in the NOD strain confirms the absence of allelic polymorphism of V beta
      coding regions.

PMID- 7519995
TI  - In vitro characterization of major ligands for Src homology 2 domains derived
      from protein tyrosine kinases, from the adaptor protein SHC and from GTPase
      activating protein in Ramos B cells.
AB  - Antigen receptors of B lymphocytes transmit their activation signal to the cell
      interior by associating with and activation of specific non-receptor tyrosine
      kinases. Most of these kinases as well as other cytoplasmic effectors contain at
      least one Src homology 2 (SH2) domain, known to bind tyrosine-phosphorylated
      proteins. We examined the binding specificity of SH2 domains from different
      signaling molecules in B cells and found that each of the SH2 domains tested
      bound distinct subsets of stimulation-dependent phosphoproteins in vitro. SH2
      domains from Src-like tyrosine kinases bound predominantly to the HS1
      phosphoprotein. The tandem SH2 domains of the ZAP-70 tyrosine kinase bound to
      phosphorylated Ig-beta but only weakly to Ig-alpha. Also the SHC-derived SH2
      domain formed complexes with the tyrosine-phosphorylated Ig-alpha/beta
      heterodimer, while the C- and N-terminal SH2 domains of GTPase-activating protein
      displayed completely different binding preferences. These results suggest that
      cytoplasmic effector molecules can be recruited to the activated B cell receptor
      in an SH2-phosphotyrosine-mediated manner. The data also provide a possible
      explanation for the notion that Ig-alpha and Ig-beta might couple to different
      biochemical pathways.

PMID- 7519994
TI  - Soluble CD14 from urine copurifies with a potent inducer of cytokines.
AB  - Here we report that soluble CD14 isolated from the urine of nephrotic patients
      (uCD14) contains a potent cytokine inducing activity. CD14 derived from urine
      appeared to consist of two major polypeptides of about 54 and 48 kDa. In uCD14
      isolated from three different nephrotic patients the cytokine-inducing activity
      appeared to co-migrate with the 48-kDa polypeptide which upon sequencing had the
      same N-terminal sequence as native CD14. Treatment of human monocytes and the
      human astrocytoma cell line U373 with uCD14 resulted in a strong secretion of
      tumor necrosis factor (TNF) and interleukin-6, respectively. The cytokine
      inducing activity of the uCD14 preparations was unaffected by the absence of
      serum. This is in contrast to the activation of human monocytes and U373 cells by
      lipopolysaccharide (LPS) which is highly dependent on the presence of serum. The
      cytokine-inducing activity was not affected by LPS-binding protein (LBP) or
      polyclonal rabbit antibodies against LBP. The TNF-inducing activity of uCD14 was
      also heat labile in contrast to the cytokine-inducing activity of LPS, which was
      relatively heat resistant. The results suggest that CD14 may exist in at least
      two forms of which one is involved in cytokine induction.

PMID- 7519996
TI  - Human RANTES induces the migration of human T lymphocytes into the peripheral
      tissues of mice with severe combined immune deficiency.
AB  - The human cytokine, Recombinant Human Regulated on Activation, Normal T Expressed
      and Secreted (rhRANTES), is a small glycoprotein secreted by activated T cells
      and platelets and is structurally related to a family of chemotactic cytokines
      called chemokines. Evaluation of the effects of chemokines on human cells has
      largely been limited to in vitro binding assays. In an effort to study the in
      vivo effects of chemokines on human leukocyte migration, we examined the ability
      of rhRANTES to induce human T cell infiltration using a human/severe combined
      immune deficient (SCID) mouse model. SCID mice received human peripheral blood
      lymphocytes, followed by sequential subcutaneous injections of rhRANTES in the
      hind flank for 3 days. The skin and underlying tissue from the rhRANTES injection
      site were then biopsied and examined for the extent of human mononuclear cell
      infiltration. rhRANTES induced significant mononuclear cell accumulation 72 h
      after injection. Immunohistological evaluation determined that the majority of
      the cells recruited in response to rhRANTES injections were human CD3+ T cells
      with equal numbers of CD4+ and CD8+ cells. In contrast, subcutaneous injections
      of recombinant human macrophage colony-stimulating factors resulted in little
      human cellular infiltration. Murine mononuclear cell infiltration in response to
      rhRANTES was also present suggesting that the in vivo effects of rhRANTES may be
      both direct and indirect. These results demonstrate that rhRANTES induces
      significant human T cell migration in vivo and suggests that the human/SCID mouse
      model may provide an important tool in studying the in vivo effects of chemokines
      on human leukocytes and leukocyte subsets.

PMID- 7519997
TI  - Monoclonal antibodies to murine CD40 define two distinct functional epitopes.
AB  - Two rat IgG2a antibodies which define distinct epitopes on murine CD40 have been
      generated. These antibodies specifically bind recombinant murine CD40 expressed
      on L cells, and the soluble extracellular domain of murine CD40 coated onto
      microtiter plates. Both antibodies bind B220+ but not B220 murine spleen cells,
      and immunoprecipitate a 45-kDa protein from the surface of purified murine
      splenic B cells. These antibodies exhibit separate functional properties,
      consistent with the notion that they define two distinct CD40 epitopes. One of
      the monoclonal antibodies (designated 1C10) directly induces a specific
      proliferative response from mature murine B cells, up-regulates several B cell
      surface antigens, and rescues immature B lymphoma cells from anti-IgM-induced
      growth arrest. The other monoclonal antibody (designated 4F11) exhibits none of
      these properties, but is capable of synergizing with suboptimal amounts of either
      anti-IgM antibodies or the 1C10 agonistic anti-CD40 antibody to produce an
      optimal proliferative response of purified small dense B cells. Furthermore, 4F11
      antibody synergizes with suboptimal amounts of 1C10 antibody to rescue B lymphoma
      cells from anti-IgM-induced growth arrest. The 1C10 and 4F11 antibodies were
      unable to cross-block each other's binding to recombinant CD40 expressed in L
      cells, providing strong support for the notion that the antibodies recognize
      distinct epitopes on CD40. The potential implications of two functionally
      distinct CD40 epitopes are discussed.

PMID- 7519998
TI  - Properties of mouse CD40: cellular distribution of CD40 and B cell activation by
      monoclonal anti-mouse CD40 antibodies.
AB  - We describe here the derivation of a rat monoclonal antibody (mAb) against mouse
      CD40 (designated 3/23), which stains 45-50% of spleen cells of adult mice,
      approximately 90% of which are B cells. Interestingly, some 5-10% of both CD4+
      and CD8+ T cells in the spleens of (some, but not all) adult, unimmunized mice
      are also CD40+, whereas CD40+ cells were not detectable in the thymus, even
      following collagenase digestion. Some 35-40% of lymphoid cells in the bone marrow
      of adult mice are CD40+ and virtually all of these are B220+, and hence of the B
      cell lineage: triple-color flow cytometry showed that CD40 is expressed at low
      levels on some 30% of pre-B cells, at intermediate levels on 80% of immature B
      cells and on essentially all mature B cells in the bone marrow. These results,
      therefore, suggest that in the mouse CD40 is expressed relatively late during the
      process of B cell differentiation. The mAb induced marked up-regulation of major
      histocompatibility complex class II molecules, CD23 and B7.2 antigens on mature B
      cells. It also stimulated modest levels of DNA synthesis in mature B cells by
      itself: this was markedly enhanced by suboptimal concentrations of mitogenic (but
      not non-mitogenic) anti-mu and anti-delta mAb, and moderately enhanced by co
      stimulation with interleukin-4. Hypercross-linking of CD40 (using biotinylated
      mAb and avidin) also enhanced the proliferative response to anti-CD40.

PMID- 7520000
TI  - Double-negative thymocyte subsets in CD3 zeta chain-deficient mice: absence of
      HSA+CD44-CD25- cells.
AB  - Double-negative (DN) thymocyte subsets were examined in mice deficient in the CD3
      zeta chain (zeta-/-). The HSA+CD44-CD25- subset was found to be missing, and DN
      thymocytes seemed to differentiate directly from HSA+CD25+CD44- cells to double
      positive (DP) cells. When fetal thymic ontogeny was examined, we found a marked
      difference between zeta-/- embryos and heterozygous littermates from embryonic
      day 17.5, in terms of CD25, CD4 and CD8 expression, and thymus size. The zeta-/-
      thymocytes failed to down-regulate CD25 and to expand exponentially. The cell
      cycle status of adult thymocyte subsets indicated that although the HSA+CD25-CD44
      subset was missing, the CD25+ DN population contained normal numbers of cycling
      cells, and the CD25+ DP cells (which were not detectable in normal mice)
      contained 5-10% cells in G2/M+S. Taken together these data suggest that the CD3
      zeta chain might have a specific role in the control of proliferation of DN
      thymocytes during T cell development. Our data clearly show that one can
      dissociate the signal for a CD25+ DN cell to differentiate (which occurs in the
      absence of CD3 zeta), from a signal to proliferate and from loss of cell surface
      CD25.

PMID- 7520002
TI  - CD14 is expressed and functional in human B cells.
AB  - The human B cell line RPMI 8226 exhibits variable staining with the CD14 antibody
      My4. We have isolated three stable clones from this line with clones 1 and 2
      being My4 positive and clone 3 My4 negative. Similar to previous results in
      monocytes, immunoprecipitation with the My4 antibody revealed a 54-kDa cell
      surface molecule, analysis of supernatants showed soluble CD14, and Northern
      blotting demonstrated a 1.4-kb transcript in clones 1 and 2, but not in clone 3,
      which suggests that the My4 antibody detects CD14 in clones 1 and 2. This CD14
      molecule was functional in that lipopolysaccharide stimulation induced
      interleukin (IL)-6 and IL-10 in clones 1 and 2 but not in clone 3. Furthermore,
      the My4 antibody was capable of blocking these responses at the transcript and
      protein levels. Finally, peripheral blood B cells were highly purified by cell
      sorting (> 98% CD19 positive). These cells produced IL-6 in response to
      lipopolysaccharide, and this response was blocked by anti-CD14 antiserum. Thus,
      our findings demonstrated that human B cells can express functionally active
      CD14.

PMID- 7520001
TI  - Neuropeptides are potent modulators of human in vitro immunoglobulin E synthesis.
AB  - We determined the effect of adrenocorticotropin hormone (ACTH) on the regulation
      of IgE synthesis. Depending on the concentration, ACTH enhanced or inhibited IgE
      synthesis in a culture system where IgE synthesis was induced with interleukin-4
      (IL-4) and anti-CD40 monoclonal antibody in peripheral blood mononuclear cells.
      Similar effects on IgE synthesis were observed by adding ACTH-related peptides,
      e.g. corticotropin-releasing factor (CRF), the inducer of ACTH, or alpha
      melanocyte stimulating hormone (alpha-MSH), a cleavage product of ACTH. However,
      ACTH had no effect on IgG or IgM synthesis in this culture system. ACTH did not
      act directly on either B or T cells as there was no influence on IgE synthesis in
      a system using purified B cells alone or co-cultured with T cells. The effect of
      ACTH on IgE synthesis was mediated by accessory cells. This was shown by priming
      purified CD14-positive monocytes with ACTH and reconstitution experiments.
      Therefore, these findings suggest that ACTH and the related peptides CRF and
      alpha-MSH can influence the microenvironment modulating an IL-4 and anti-CD40
      monoclonal antibody driven class switching to IgE via accessory cells.

PMID- 7520003
TI  - Nitric oxide synthase: mRNA expression of different isoforms in human
      monocytes/macrophages.
AB  - To detect mRNA expression of nitric oxide synthase (NOS) isoforms in human
      monocytes/macrophages reverse transcription polymerase chain reaction (RT-PCR)
      was used. mRNA was isolated from stimulated or unstimulated monocytes/macrophages
      and RT-PCR was performed using oligonucleotide primers derived from mRNA
      sequences of either human endothelial constitutive (c) or human hepatocyte
      inducible (i) NOS. RT-PCR of mRNA isolated from resting monocytes and macrophages
      resulted in the amplification of a cNOS specific mRNA fragment. When the cells
      were stimulated with lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) prior
      to mRNA extraction, RT-PCR yielded an iNOS-specific amplification product.
      Whereas the activation of both cell types was accompanied by expression of iNOS
      mRNA, the cNOS signal seemed to be diminished upon immunostimulation. Not only in
      purified human monocytes but also in the human monocytoid cell lines MonoMac 6,
      THP-1, and U937 cNOS mRNA was detected. The data clearly demonstrate the presence
      of iNOS and cNOS mRNA in human monocytes/macrophages and provide the necessary
      tools to investigate the regulation of NO synthesis in these cell populations.

PMID- 7519999
TI  - T cell specialization at environmental interfaces: T cells from the lung and the
      female genital tract of lpr and gld mice differ from their splenic and lymph node
      counterparts.
AB  - Mice homozygous for lpr and gld accumulate CD4- CD8- (double-negative, DN) B220+
      CD5loThy-1lo alpha beta T cells in the spleen and lymph nodes (LN), while mucosal
      gut T cells are normal. To study other mucosa-associated T cell populations, we
      examined T cell subsets separated according to expression of alpha beta T cell
      receptor, CD4, CD5, CD8, Thy-1 and B220 in the lung and the female genital tract
      (FGT) of adult MRL lpr, C3H lpr and C3H gld mice. alpha beta T cell accumulation
      was detected in both the FGT and the lungs of lpr and gld mice but, in contrast
      to the spleen and LN, equal proportions of DN B220+ and CD4+ of CD8+ (single
      positive, SP) B220- T cells were observed in these sites, and the T cells had an
      increased expression of Thy-1 and CD5. Staining for CD44, L-selectin, and CD45RB
      revealed a higher percentage of effector/memory T cells in lpr and gld lungs and
      FGT compared to spleens and LN. CD69 expression suggested chronic activation of
      DN and SP T cells in lpr and gld lungs and FGT. Thus, we show that FGT and lung
      resident T cells are affected by lpr and gld mutations, but that their phenotypes
      are distinct from those of systemic T cells. These data suggest that T cells
      associated with FGT and lung mucosal tissues represent a separate lineage from
      systemic T cells, and/or that the abnormal T cells in lpr and gld mice are
      selected against in mucosal surfaces exposed to environmental antigen.

PMID- 7520004
TI  - In vivo-effect of intraadrenal nicotine and substance P application on rat
      adrenal medullary catecholamine secretion.
AB  - The present study was conducted to characterize in vivo the intraadrenal
      catecholamine (CA) secretion in rats. This was possible by using a microdialysis
      system (MDS) which mimics some properties of an artificial capillary. One end of
      this system was connected to a peristaltic pump, from the other end fractions
      were sampled at 5 min intervals. Concentrations of epinephrine (E) and
      norepinephrine (NE) in adrenal dialysate fractions were determined by HPLC
      electrochemical detection. Through this MDS nicotine was administered directly
      into the adrenal medulla of freely moving rats and the response of catecholamine
      release was determined. In the second part of the study the effect of exogenous
      substance P (SP) on spontaneous as well as on nicotine-stimulated CA release was
      investigated. Like nicotine, SP was administered directly into the adrenal
      medulla. At a flow rate of 25 microliter/min the transfer rates of CA and
      nicotine were approximately 1% whereas SP passed at a rate of 01.-0.2%. Under
      resting conditions CA release remained constant. In response to 2 x 10(-7) M
      nicotine (which resulted in local concentration of 2 x 10(-7) M), E and NE
      secretion increased 2.9 and 5.4-fold, respectively. However, due to an increased
      E response this difference attenuated with a later onset of the first stimulus.
      The higher concentrations of 10(-4) M resulted in 8.1 and 10.8-fold increases for
      E and NE. This latter response is clearly supraphysiologic and therefore the 2 x
      10(-5) M concentration was used for further experimentation. CA secretion was
      stimulated with nicotine four times at 30 min intervals.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7520005
TI  - Pathogenesis of onchocercal dermatitis: possible role of parasite proteases and
      autoantibodies to extracellular matrix proteins.
AB  - We examined the immunogenicity of various connective tissue proteins in patients
      with chronic onchocercal dermatitis and the effect of filarial proteases on this
      host-parasite interaction. Sera from patients with onchocerciasis reacted
      strongly with cuticular collagens from filarial parasites and with mammalian
      laminin. Some sera also contained antibodies to elastin and collagen type IV, but
      none reacted with collagen types I-III or fibronectin. This pattern of reactivity
      was characteristic for onchocerciasis: sera from patients with mansonellosis
      reacted strongly with collagen type IV but only weakly with laminin. Reactivity
      with mammalian laminin or collagen could not be absorbed with cuticular proteins
      from filarial worms and vice versa. Digestion fragments of laminin treated with
      filarial proteases retain antigenic determinants recognized by sera from patients
      with onchocerciasis. In contrast, proteases from Onchocerca volvulus adults and
      microfilariae drastically decreased the reactivity of the same sera with collagen
      type IV. These results indicate that filarial proteases may contribute to the
      pathogenesis of chronic onchocercal dermatitis, directly, by enzymatically
      destroying connective tissue of the skin, and indirectly, by triggering
      autoimmune responses to self-determinants on connective tissue proteins that are
      normally hidden within the supramolecular structure of the extracellular matrix
      complex.

PMID- 7520006
TI  - Assessment of a method of determining ribonuclease activity employing RNA as
      substrate.
AB  - An evaluation of the analytical performance of a method for determining
      ribonuclease catalytic activity employing digestion of RNA substrate was made. It
      was found that the relationship between concentrations of ribonuclease standards
      and concentrations of the reaction products, expressed as the 260 nm light
      absorbance values, was nonlinear and fulfils a binomial function. Substituting
      ribonuclease activities by square roots of ribonuclease activity values, a linear
      relationship with light absorbance values, ranging from 0.08 to 0.400 was
      obtained. In the present work one unit of ribonuclease catalytic activity was
      defined as RNA-degrading activity which in the assay conditions caused A260 equal
      to 0.332. The general equation of the ribonuclease catalytic activity was:
      Ribonuclease (U/l) = [(A260 - 0.02)/0.316]2. In spite of the nonlinearity of the
      standard curve, the actual CV values did not depend essentially on the value of
      measured activity and were estimated as 13%.

PMID- 7520007
TI  - FK 506/fluconazole interaction enhances FK 506 nephrotoxicity.
AB  - In a diabetic liver transplant recipient, immunosuppressed with FK 506, a severe
      digestive moniliasis required treatment with the antifungal imidazole derivative
      fluconazole. This was followed by a brisk rise in serum creatinine levels, which
      returned promptly to baseline when this combination was stopped. Serial
      measurements of FK 506 concentrations in plasma showed excessive areas under the
      24 h time-concentration curve and trough levels during the concomitant intake of
      imidazole antifungals and FK 506. Eighteen months later, this patient presents
      with normal renal function. Antifungal imidazole derivatives inhibit the P 450
      cytochrome enzyme system and may thus decrease the catabolism of FK 506.
      Meticulous monitoring of FK 506 trough levels and dosage adaptation are
      compulsory when concomitant treatment with such a drug is unavoidable. The same
      is true for cyclosporine in auto-immune diabetic patients receiving cyclosporine
      A.

PMID- 7520009
TI  - Autocrine growth factors produced in the thyroid.
AB  - This catalogue of autocrine growth factors is limited to proteins--metabolites of
      iodine and prostaglandins are omitted and they are undoubtedly of autocrine
      importance in the thyroid, as elsewhere. However, this summary of polypeptide
      growth factors secreted by the thyroid illustrates the potential cells have to
      condition their environment to modify their responses to external stimuli. This
      enables cells in different tissues to respond to agonists in different ways. The
      effects of TSH on IGF, IGFBP and IGF receptor production and the effects of
      IGFBPs on IGF action are good examples of this amplified response. Many pieces of
      the jigsaw, however, remain to be found and put in place before a clear picture
      of the regulation and roles of these factors can be made.

PMID- 7520008
TI  - The biochemistry of endemic cretinism: roles of iodine and selenium deficiency
      and goitrogens.

PMID- 7520010
TI  - A partition coefficient determination method for nonvolatile chemicals in
      biological tissues.
AB  - Partition or distribution coefficients are critical elements in efforts designed
      to describe the uptake, distribution, biotransformation, and excretion of organic
      chemicals in biological systems. In order to estimate the partition coefficients
      needed to describe the biological distribution of low-volatility compounds, an
      experimental method was developed to measure partitioning of nonvolatile
      compounds into biological tissues. Blood, fat, muscle, liver, and skin were
      individually incubated in a saline solution containing the chemical of interest.
      Each sample was centrifuged and 2.0 ml of the supernatant was removed and placed
      into a prewashed, low binding 10,000 MW cutoff Millipore filter cell. Each cell
      was fitted with a magnetic stirrer and 32 psi nitrogen was applied to the closed
      cell. The filtrate was collected, extracted, and analyzed for the chemical of
      interest. The chemicals evaluated were parathion, lindane
      (hexachlorocyclohexane), paraoxon, perchloroethylene, trichloroacetic acid, and
      dichloroacetic acid. These chemicals were chosen to develop this method because
      their vapor pressures range from 9 x 10(6) to 14.2 mm Hg at 20 degrees C. For the
      one volatile chemical evaluated, perchloroethylene, the method provided partition
      coefficient results that were in good agreement with values obtained using the
      vial equilibration method. The nonvolatile partition coefficient method described
      in this paper demonstrates an approach for evaluation of chemicals with diverse
      chemical structure and solubility properties.

PMID- 7520012
TI  - Characterization of a Y-Box factor from Aplysia californica.
AB  - A cDNA isolated from the marine invertebrate Aplysia californica encodes a
      protein containing a domain with a high degree of homology to the Y-Box-binding
      factors. The expression of this gene is unaffected by the facilitatory
      neurotransmitter, 5-hydroxytryptamine. When expressed in Escherichia coli, the
      encoded protein is shown to bind RNA in vitro.

PMID- 7520011
TI  - Dilation of esophageal strictures induced by radiation therapy for cancer of the
      esophagus.
AB  - During a 2-year period, 103 consecutive patients undergoing dilation of
      esophageal strictures induced by radiation therapy for cancer of the esophagus
      were prospectively studied. The length of the strictures ranged from 0.5 to 13.5
      cm (median, 5 cm) and the luminal diameter from 1 to 11 mm (median, 6 mm).
      Patients were referred for dilation from 2 weeks to 5 years (median, 2 months)
      after completion of radiation therapy. The guide wire was placed using
      fluoroscopy in 21 patients, endoscopy in 61, and a combination of endoscopy and
      fluoroscopy in 21. At least one dilator larger than the stricture could be passed
      in 101 (98%) patients. Five strictures were dilated to 16 mm, 29 to 15 mm, 28 to
      14 mm, 16 to 12.8 mm, and 23 to 12 mm or less during the initial procedure.
      Development of complications and severe resistance were the limiting factors for
      optimal dilation. Relief of dysphagia was adequate in 66% of patients. The
      duration of dysphagia relief was 3 to 84 weeks (median, 16 weeks). Complications
      included persistent pain in 7 patients, unexplained fever in 2, perforation in 2,
      and delayed tracheo-esophageal fistula in 1. Two patients died of treatment
      related complications. Repeated dilation was required in 32 of the 75 patients on
      long-term follow-up. We conclude that adequate palliation of dysphagia can be
      achieved by dilation in two-thirds of patients with radiation therapy-induced
      strictures of the esophagus. Dilation of these strictures is relatively simple
      and safe if performed with care.

PMID- 7520013
TI  - Cloning, sequence comparison and in vivo expression of the gene encoding rat P
      selectin.
AB  - We have cloned the cDNA encoding rat P-selectin (Psel) and have examined the
      regulation of Psel expression in vivo. Sequence analysis of the complete Psel
      cDNA demonstrated significant nucleotide and amino-acid identity with human and
      mouse Psel. Similar to mouse Psel, the rat sequence lacks the equivalent of human
      complement regulatory protein-like repeat 2 (CR2). Seven potential N-linked
      glycosylation sites are conserved between the three species, suggesting that
      carbohydrate modification may play an important role in Psel function. To examine
      expression of Psel in vivo, levels of Psel mRNA were examined in several
      different tissues after systemic administration of lipopolysaccharide (LPS). Psel
      mRNA was undetectable in tissues of vehicle-treated animals. By 3 after LPS
      administration, Psel mRNA levels were elevated in all tissues examined, the
      highest levels being seen in the lung. Significant increases in Psel mRNA were
      also seen in the heart, thymus, spleen and kidney. By 24 h after LPS, mRNA levels
      for Psel remained elevated in the lung, heart, kidney, thymus and small
      intestine. Psel mRNA was not detectable in total RNA isolated from purified rat
      platelets, suggesting that the increased levels of Psel mRNA were the result of
      upregulation of endothelial gene expression. In addition, only minimal levels of
      platelet factor 4 mRNA (PF4), used as a platelet-specific marker, were observed
      in the tissues studied. These data demonstrate that part of the response to acute
      inflammation in vivo includes the rapid increase in endothelial Psel expression.

PMID- 7520014
TI  - Increase in serum alpha-fetoprotein without recurrent disease after hepatectomy
      for hepatocellular carcinoma.
AB  - The case of a 58-year-old man with clinically-stable and compensated HBsAg
      positive liver cirrhosis is reported. In April 1991, the patient underwent
      partial hepatectomy to treat a solitary 3.5 cm hepatocellular carcinoma (HCC),
      (Edmonson scale I), in the 5th liver segment. His serum alpha-fetoprotein (AFP)
      level was 24 ng/ml. After hepatectomy, the AFP level dropped to 8 ng/ml, but
      between the 4th and 12th month it rose gradually from 72 ng/ml to 4,520 ng/ml.
      Hepatic recurrence of HCC was excluded, but a 6 cm solitary metastasis (Edmonson
      scale III-IV) was detected on the right adrenal. Adrenalectomy was performed and
      two months later the patient is doing well and his AFP level is 51 ng/ml. The
      methodological approach to diagnosis, treatment and follow-up of HCC, and the
      relationship between AFP and liver and metastatic HCC, are discussed.

PMID- 7520015
TI  - Desmin and neural marker expression in mesothelial cells and mesotheliomas.
AB  - The distribution of keratin, vimentin, desmin, muscular actin, S100, specific
      neuron enolase, and chromogranin was studied by immunoperoxidase staining in
      mesothelium, malignant mesotheliomas, and pulmonary carcinomas. The mesothelial
      cells were positive for keratin and vimentin on all smears of pleural and ascitic
      effusions; most of them were also positive for desmin but rarely for enolase and
      S100. None was positive for muscular actin. Sixteen malignant mesotheliomas
      expressed vimentin and keratin; six were also positive for desmin, three for
      desmin and neural markers, and five for neural markers. In comparison, none of
      the pulmonary carcinomas was positive for these markers. Mesothelial cells are
      able to express markers of divergent differentiation. Mesotheliomas also have
      such markers that are present in other malignant tumors and, in particular, in
      intra-abdominal desmoplastic small cell tumors with divergent differentiation.
      This entity and mesotheliomas probably originate from the same cell. Moreover,
      desmin, found in 56% of malignant mesotheliomas but absent in pulmonary
      carcinomas, may be useful in the differential diagnosis of these tumors.

PMID- 7520016
TI  - In situ localization of Epstein-Barr virus encoded RNA in non
      nasal/nasopharyngeal CD56-positive and CD56-negative T-cell lymphomas.
AB  - We recently reported a group of non-nasal/nasopharyngeal hematolymphoid
      malignancies expressing the natural killer cell marker CD56, characterized by
      frequent extranodal localization, angiocentricity, and aggressive clinical course
      (HUM PATHOL 23:798-804, 1992). Because we have shown a very strong association of
      Epstein-Barr virus (EBV) with CD56-positive T-cell lymphomas of the nose
      nasopharynx, we asked whether a similar association also occurs with the non
      nasal CD56-positive T-cell lymphomas. In situ localization of EBV encoded RNA
      (EBER) was performed on paraffin sections of 15 such cases, including the nine
      previously reported cases and six new cases (three showing prominent
      hepatosplenic involvement and three showing involvement of one or more extranodal
      sites, such as the parotid gland, tonsils, gastrointestinal tract, skeletal
      muscle, and testis). A case was considered positive when the majority of the
      tumor cells showed nuclear signal. Ten cases showed EBER positivity, and all but
      one of them were negative for CD3 and other T-cell markers, except CD2. Only one
      of four cases showing a CD3-positive phenotype was EBER positive. Of the
      remaining two CD3-negative EBER-negative cases, one showed a histiocytic
      phenotype and the other was positive for multiple T-cell markers. Among 15 cases
      of CD56-negative non-nasal peripheral T-cell lymphoma studied for comparison, six
      were CD3-negative, among which three showed EBER positivity. All nine CD3
      positive cases were EBER negative. Five cases (three CD3 positive and two CD3
      negative) showed rare isolated (< 1%) EBER-positive tumor cells. We conclude that
      among non-nasal T-cell lymphomas, EBV is strongly correlated with CD56 positivity
      (66.7% v 20%), and the positive cases almost always show an immunophenotype
      identical to that commonly observed in nasal lymphomas (CD2 positive, CD3
      negative, and CD56 positive). Thus, EBV may play an etiologic role in these CD56
      positive lymphomas. There is also a correlation between EBER positivity and CD3
      negativity, irrespective of the CD56 status. The presence of isolated EBER
      positive cells in CD56-negative T-cell lymphomas, occurring at a frequency
      similar to that reported in the European population, probably represents
      secondary infection of tumor cells.

PMID- 7520017
TI  - CD34 expression by gastrointestinal tract stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are neoplasms arising in the wall of the
      gastrointestinal tract that frequently show evidence of smooth muscle
      differentiation, either by their appearance alone or by immunohistology. A
      significant number of these neoplasms fail to react with any markers of muscle
      differentiation, however. A subset of these neoplasms have epithelioid features,
      and the presence of these features can give rise to confusion with other
      neoplasms, such as carcinomas and melanomas. Here we show that the CD34
      monoclonal antibody My10 reacts with 19 of 23 (83%) of these lesions, including
      both those with and without epithelioid features. Five of 10 epithelioid and one
      of 13 spindled neoplasms lacked detectable muscle-specific actin (MSA), smooth
      muscle actin (SMA), and desmin; all six were CD34 reactive. Immunoblotting
      experiments show that the antigen on these stromal neoplasms has a molecular
      weight identical to that found on hematopoietic cells. The frequency and
      intensity of the reactivity of GISTs with anti-CD34 antibodies are distinctly
      higher than those reported for smooth muscle neoplasms of soft tissue and
      myometrium. This reactivity can be a useful adjunct in the diagnosis of difficult
      cases, especially in those exhibiting epithelioid morphology.

PMID- 7520018
TI  - Bone marrow involvement by lobular carcinoma of the breast cannot be identified
      reliably by routine histological examination alone.
AB  - The aims of this study were twofold: (1) to evaluate the ability of pathologists
      to recognize infiltration of bone marrow core biopsy specimens by breast
      carcinoma, particularly lobular carcinoma, using routine hematoxylin-eosin (HE)
      sections; and (2) if indicated, to determine the reasons for difficulties in
      diagnosis. Thirty-six bone cores obtained before bone marrow harvest were
      involved by breast carcinoma and were confirmed by pancytokeratin immunostains.
      Thirty of the 36 were ductal carcinomas and six were lobular carcinomas. Fourteen
      negative bone core biopsy specimens (from patients with breast cancer or
      lymphoma) were included as controls. These 50 bone cores were reviewed by three
      surgical pathologists. Lobular carcinoma was correctly identified in only 39% of
      positive specimens as compared with 88% for ductal carcinoma. After instruction,
      sensitivity for the detection of lobular carcinoma improved to 61% but at the
      expense of an unacceptably high rate of false-positive diagnoses (18%). None of
      the three pathologists was able to achieve both high sensitivity and high
      specificity in recognizing lobular carcinoma in the bone marrow. Lobular
      carcinoma was difficult to detect because of tumor cell size similar to
      hematopoietic cells, infiltration as single cells, presence of bland cytological
      features, and paucity of tissue reaction to the tumor. Although the number of
      cases of bone marrow involved by lobular carcinoma is small, these findings
      suggest that pancytokeratin stains should be performed routinely in the
      evaluation of bone core biopsy specimens from patients with lobular carcinoma,
      and probably from patients with ductal carcinoma whose HE-stained bone core
      biopsy specimens are considered negative for tumor.

PMID- 7520019
TI  - Apoptosis and expression of the bcl-2 proto-oncogene in the fetal and adult human
      kidney: evidence for the contribution of bcl-2 expression to renal
      carcinogenesis.
AB  - bcl-2 was identified as a transcript associated with the t(14;18) and imparts
      resistance to apoptotic cell death. bcl-2 is normally expressed in many tissues
      and exhibits remarkable structural and functional conservation. Using
      immunohistochemical and in situ DNA labeling techniques we examined the
      localization of bcl-2 in the developing human kidney. bcl-2 expression was
      rapidly upregulated in the induced metanephrogenic mesenchymal cells that
      differentiate into renal vesicles and nephrons. bcl-2 expression was undetectable
      in uninduced mesenchyme and in the renal ampullae and associated collecting
      system. The distribution of apoptotic cells within the developing kidney was
      inversely correlated with expression of bcl-2. The localization of bcl-2 protein
      in the adult human kidney also was examined. bcl-2 was expressed at high levels
      in all renal neoplasms examined providing a potential basis for the deregulation
      of apoptosis in the development and progression of these tumors.

PMID- 7520020
TI  - Frequency of apoptotic bodies positively correlates with Gleason grade in
      prostate cancer.
AB  - Tissue samples from patients with carcinoma of the prostate of various Gleason
      grades were examined for the frequency of apoptotic bodies. Apoptotic bodies were
      scored by morphometric methods using hematoxylin-eosin (HE)-stained sections from
      surgical specimens of prostate cancer. Non-neoplastic prostate tissue adjacent to
      foci of cancer showed a very low frequency of apoptotic bodies. Significantly
      larger numbers of apoptotic bodies were observed in the areas of carcinoma than
      in the non-neoplastic control tissues, regardless of Gleason grade.
      Interestingly, a positive correlation was noted between apoptotic bodies and
      increasing Gleason grade. The positive correlation suggests that increased
      programmed cell death is a feature of the increasing malignant potential that is
      associated with higher Gleason grade in prostate cancer.

PMID- 7520022
TI  - A new missense mutation G1249E in exon 20 of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene.

PMID- 7520021
TI  - Consensus statement on terminology: recommendation to use atypical adenomatous
      hyperplasia in place of adenosis of the prostate.

PMID- 7520023
TI  - Microtubule-associated protein 1B (MAP1B) is present in glial cells
      phosphorylated different than in neurones.
AB  - A panel of four anti-MAP1B antibodies have been used to study the presence and
      post-translational modification of MAP1B in primary cultures of glial cells. Two
      antibodies (150 and 125) recognize phosphorylated epitopes whereas the other two
      (531 and 842) recognize non-phosphorylated phosphorylatable epitopes on the MAP1B
      molecule. Immunofluorescence and Western blot analysis with antibodies 531 and
      842 revealed the presence of small amounts of MAP1B-like immunoreactivity in type
      1 astrocytes and a greater content in more differentiated glial cells found in
      long-term cultures. By immunofluorescence, these latter cells gave positive
      immunostaining with antibody 125, which recognizes a phosphorylated epitope
      phosphorylated by casein kinase II. Antibody 150, which reacts to a
      phosphorylated epitope on the MAP1B molecule, did not show any detectable
      immunoreactivity in glial cells cultures, either by immunofluorescence or Western
      blot. All four antibodies recognized hippocampal neurones in culture, with
      especially intense immunostaining in cell bodies and axons, and reacted strongly
      with protein present in hippocampal neurones extracts showing an electrophoretic
      mobility similar to that of brain MAP1B. In mixed optic nerve glial cell
      cultures, anti-galactocerebroside (GalC) positive cells gave also positive
      staining with antibodies 531 and 125. We propose that MAP1B is present in
      cultures of glial cells in moderate amounts and with a phosphorylation state
      different than in neurones. Thus, less differentiated glial cells, such as type 1
      astrocytes, have a small amount of MAP1B, mainly in a non-phosphorylated form,
      which is spread diffusely in the cytoplasm and probably does not interact with
      microtubules. More differentiated glial cells, such as oligodendrocytes, show a
      greater content in MAP1B which, at least in part, is phosphorylated by a casein
      kinase II-like activity.

PMID- 7520024
TI  - Myelin-associated glycoprotein is not detectable in perikaryal myelin of spiral
      ganglion neurons of adult mice.
AB  - The expression of the adhesion molecules N-CAM (neural cell adhesion molecule),
      L1, myelin-associated glycoprotein (MAG), and P0 has been investigated by
      postembedding-immunoelectron microscopy in spiral ganglia of adult mice in which
      both axons and neuronal cell bodies are myelinated. L1 was absent from both
      axonal and perikaryal myelin of spiral ganglion neurons but was expressed on
      unmyelinated nerve fibers. P0 was expressed in compacted parts of both types of
      myelin but was absent from non-compacted myelin. MAG was not detectable in
      perikaryal myelin but was strongly expressed in axonal myelin both periaxonally
      and in non-compacted regions. Conversely, N-CAM was detectable at the interface
      between myelin and neuronal perikarya and in non-compacted regions of perikaryal
      myelin, whereas it was hardly detectable in axonal myelin. This inverse
      expression of MAG and N-CAM in perikaryal and axonal myelin points to the
      possibility that N-CAM may functionally replace MAG in perikaryal myelin of
      spiral ganglion neurons.

PMID- 7520025
TI  - Confocal imaging of glial cells in the intact rat optic nerve.
AB  - Astrocytes and oligodendrocytes in the isolated intact mature rat optic nerve
      have been computer imaged in three dimensions by laser scanning confocal
      microscopy of single cells, dye-filled with lysinated rhodamine dextran (LRD).
      Our results illustrate the first application of these techniques to an intact CNS
      white matter tract and provide comparative data for previous studies on neonatal
      rat optic nerve (Butt and Ransom: Glia 2:470-475, 1989; Butt and Ransom: J Comp
      Neurol 338:141-158, 1993). The combined use of intracellular injection of LRD and
      confocal imaging significantly improves the resolution of glial cell structure,
      particularly that of mature astrocytes, for a number of reasons. 1) Single mature
      dye-filled glia can be imaged, because LRD does not pass through gap junctions.
      2) The entire process field of astrocytes can be visualized in a single two
      dimensional image. 3) Cell images can be rotated through 360 degrees in all
      planes to provide a new perspective of glial cell structure in the intact tissue.
      4) Reconstruction of optical sections, within a narrow focal plane, provides a
      high definition and resolution of the finer details of glial morphology. Using
      these techniques, three astrocyte subclasses were distinguished on morphological
      criteria. It is the conclusion of this study that the majority of these forms
      represent a single population of fibrous astrocytes which are well-suited to
      perform the multiple functions attributed to astrocytes in the CNS. The
      morphology of mature myelin-forming oligodendrocytes was also described.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7520026
TI  - Expression of the co-stimulatory molecule B7 on melanoma cells.
AB  - The induction of T-cell responses against tumor cells is believed to depend on
      both recognition of antigen and receipt of co-stimulatory signals from
      interaction of ligands such as B7 with its receptors CD28 or CTLA-4 on T cells.
      In the present study the expression of B7 on cultured human melanoma cells was
      studied at the mRNA level by reverse PCR analysis and surface expression by flow
      cytometric analysis with monoclonal antibodies (MAbs). PCR analysis revealed mRNA
      for B7 in 3 of 6 (50%) cultured primary melanoma and 8 of 19 (42%) cultures of
      metastatic melanoma. Analysis of B7 expression by flow cytometry using the BB1
      MAb revealed low levels of expression in 3 of 10 melanoma that had mRNA for B7.
      In 2 of the latter (but not 4 other PCR+ lines) expression could be increased by
      culture in GM-CSF, IL-2, IFN-gamma and IFN-alpha 2. Our results indicate that
      although mRNA for B7 is present in 40-50% of melanoma cell lines, expression at
      the protein level is at low or undetectable levels in the majority of the cell
      lines. Expression of B7 protein was also not detected in studies on tissue
      sections from 11 primary and 9 metastatic melanomas.

PMID- 7520027
TI  - Apoptotic cell death induced by a mouse-human anti-APO-1 chimeric antibody leads
      to tumor regression.
AB  - The murine anti-APO-1 antibody (gamma 3, kappa) induces programmed cell death
      (apoptosis) following binding to the APO-1 antigen (m.w., 48 kDa) expressed,
      e.g., on activated or malignant lymphocytes. APO-1 expression on malignant cell
      lines and tissues suggested potential clinical utility supported by anti-APO-1
      mediated tumor regression in a nude mouse model. A mouse-human anti-APO-1
      chimeric antibody (gamma 3, kappa) with an affinity similar to that of the murine
      antibody was produced. Chimeric anti-APO-1 showed the same potential to inhibit
      growth of the SKW6.4 B-lymphoblastoid cell line as murine anti-APO-1. In
      addition, both the chimeric and murine anti-APO-1 antibodies were equally capable
      of mediating complete macroscopic tumor regression of a SKW6.4 xenotransplant in
      SCID mice by induction of apoptosis. Induction of apoptosis was the only
      mechanism for tumor regression because neither murine nor chimeric anti-APO-1
      showed anti-tumor activity against solid H53 tumor (APO-1 antigen-positive, anti
      APO-1-resistant) xenotransplants. Our results indicate that the chimeric anti-APO
      1 antibody effectively induces apoptosis and suggest that chimeric anti-APO-1
      should be evaluated for the treatment of malignant cells expressing the APO-1
      antigen. However, chimeric anti-APO-I might only be used therapeutically when the
      antibody can be targeted specifically to tumor cells.

PMID- 7520029
TI  - Cancer pain management: 'inadequate'.
AB  - The tools and techniques needed to manage pain in a vast majority of cancer
      patients are readily available but are not being used effectively, say these Iowa
      internists. For patients with advanced malignancies, the most satisfying role
      physicians can play is to provide effective pain management.

PMID- 7520028
TI  - Stimulation of Na+,K+,Cl- cotransport by forskolin-activated adenylyl cyclase in
      fetal human nonpigmented epithelial cells.
AB  - PURPOSE: To determine the stoichiometry of Na+,K+,Cl- cotransport in fetal human
      nonpigmented ciliary epithelial cells and the effect of forskolin, an adenylyl
      cyclase activator, on Na+,K+,Cl- cotransport. METHODS: 86Rb+ as a marker for K+
      was used to study ouabain-insensitive, bumetanide-sensitive 86Rb+ uptake in
      cultured human nonpigmented epithelial (NPE) monolayers. RESULTS: The dependence
      of ouabain-insensitive, bumetanide-sensitive 86Rb+ uptake upon Na+, K+, and Cl-
      concentrations was determined. Maximal uptake was observed at about 12 mM, 20 mM,
      and 120 mM of these ions, respectively. Analysis by Hill plot suggested that the
      stoichiometry of Na+,K+,Cl- cotransport is 1:1:2, making this an electroneutral
      process. Na+,K+,Cl- cotransport was found to be stimulated approximately 1.5- to
      2-fold after incubation of cells for 15 minutes with 1 microM forskolin. neither
      ouabain-sensitive 86Rb+ uptake nor bumetanide-insensitive, ouabain-insensitive
      uptake was affected. 8-Bromoadenosine cAMP and 8-chlorophenylthio cAMP at 1 mM
      stimulated Na+,K+,Cl- cotransport approximately 30% to 40%, whereas 1,9
      dideoxyforskolin, a non-adenylyl cyclase-activating analogue of forskolin, had
      little effect. Stimulation of Na+,K+,Cl- cotransport by forskolin was blocked by
      prior exposure of cells to 10 microM H-89, a protein kinase A inhibitor.
      Stimulation by forskolin was also observed in the presence of either 1 mM DIDS,
      30 microM NPPB, 3 mM DPC, or 5 mM BaCl2, although all four channel blockers
      inhibited Na+,K+,Cl- cotransport to various degrees. CONCLUSIONS: The data
      suggest that the human NPE Na+,K+,Cl- cotransporter transports Na+, K+, and Cl-
      in the ratio of 1:1:2. Activation of adenylyl cyclase stimulates Na+,K+,Cl(-)
      cotransport via a mechanism involving protein kinase A. Reduction of Na+,K+,Cl-
      cotransport by chloride channel blockers raises the possibility that activities
      of some ion channels can influence the rate of ion influx via Na+,K+,Cl-
      cotransport.

PMID- 7520031
TI  - Benign prostatic hypertrophy.

PMID- 7520030
TI  - Prostate cancer therapy: a recipe for confusion.

PMID- 7520035
TI  - Clozapine for early developmental delays with childhood-onset schizophrenia:
      protocol and 15-month outcome.
AB  - This paper reports on the pharmacotherapy and long-term follow-up of a child
      treated with clozapine. It is one of the earliest American experiences with this
      agent in children to date. Clozapine was relatively effective and safe in this
      patient. Additional features of the case are the early social and developmental
      delays preceding schizophrenia, the response of symptoms of childhood-onset
      schizophrenia to clozapine, and the reduction in tardive dyskinesia symptoms
      while taking clozapine. Compared to recommendations for dosing adults, a slower
      rate of increasing clozapine doses was important for this child. For future
      reference, the protocol and consent form used for this course of treatment are
      included.

PMID- 7520032
TI  - Junctional uvomorulin/E-cadherin and phosphotyrosine-modified protein content are
      correlated with paracellular permeability in Madin-Darby canine kidney (MDCK)
      epithelia.
AB  - Strains I and II of Madin-Darby canine kidney (MDCK) cells, which differ markedly
      in transepithelial resistance (RT) and paracellular permeability, have been used
      to investigate whether differences in the cellular content of uvomorulin/E
      cadherin and phosphotyrosine may be correlated with junctional properties. Using
      immunocytochemistry, the strain I "tight" epithelia showed significantly stronger
      uvomorulin staining at regions of cell-cell contact compared with strain II
      "leaky" MDCK epithelia. In contrast, strain I MDCK cells showed a relatively
      faint phosphotyrosine staining, distributed evenly throughout the cytoplasm,
      while strain II MDCK cells displayed intense staining for phosphotyrosine
      residues in the junctional region and the lateral cell membrane with additional
      labelling of the cytoplasm. Exposure to vanadate in conjunction with H2O2 (which
      are potent inhibitors of protein tyrosine phosphatases) resulted in a dramatic
      increase in phosphotyrosine staining at the intercellular area and,
      concomitantly, induced changes in cell morphology, a significant decrease in RT,
      increase in paracellular inulin permeability, and time-dependent disappearance of
      uvomorulin from the cell-cell contact sites. Moreover, the effects of
      vanadate/H2O2 treatment were more dramatic in strain II compared with strain I
      cells, consistent with greater generation of tyrosine-modified protein in strain
      II cells. An inverse relationship was demonstrated between membrane-associated
      uvomorulin/E-cadherin and cellular phosphotyrosine content, which varied between
      the two strains of MDCK cells and when phosphotyrosine was directly manipulated.
      These data support the hypothesis that regulation of paracellular permeability
      may result from specific tyrosine phosphorylation of protein components of the
      junctional complex.

PMID- 7520033
TI  - Cytochemical localization of NADPH-diaphorase in the four types of pancreatic
      islet cell.
AB  - NADPH-diaphorase activity, which has been previously reported to be associated
      with the enzyme nitric oxide synthase (NOS), was localized cytochemically in the
      pancreatic islets of normal rats. All islet cells types, i.e. insulin-, glucagon
      , somatostatin- and pancreatic polypeptide-immunoreactive cells, expressed NAD-PH
      diaphorase histochemical activity, whereas the exocrine tissue was almost
      negative. In streptozotocin-treated rats, only the surviving non-beta cells in
      the islet periphery were stained. Isolated beta and non-beta cells also expressed
      intense NADPH-diaphorase activity. By electron microscopy, the enzyme was
      localized primarily on membranes of the endoplasmic reticulum and nuclear
      envelope, as previously reported for neurons. In addition the enzyme activity was
      found in the cis-region of the Golgi complex. These results suggest that the four
      types of endocrine cells of the islets of Langerhans may contain the NOS-enzyme
      and thus constitutively produce nitric oxide.

PMID- 7520036
TI  - Differential induction of adult and fetal globin gene expression in the human CML
      cell subline KU-812F/33.
AB  - Various chemicals which are known to have positive effects on differentiation of
      some erythroid cell lines were tested on a human chronic myelogenous leukemia
      cell line, KU-812F. Succinic acid, 5-azacytidine, daunomycin, and hemin showed a
      positive effect. Among them, hemin and 5-azacytidine were the most effective
      inducers for erythroid differentiation of KU-812F cells. Dimethylsulfoxide,
      cytosine arabinofuranoside, and sodium n-butyrate showed no effect. In addition,
      subclone KU-812F/33 derived from the KU-812F cell line showed differential
      expression of the beta- and gamma-globin genes in the presence of either 2 microM
      5-azacytidine or 40 microM hemin. Hemoglobin synthesis in differentiated KU
      812F/33 cells was analyzed by isoelectric focusing gel electrophoresis, and S1
      mapping analysis of beta- and gamma-globin mRNA was performed. After treatment
      with 5-azacytidine, the beta-globin gene expression was predominantly enhanced
      (18.75-fold higher level of beta-globin mRNA). After treatment with hemin, the
      most notable increase was in the gamma-globin gene expression (1.83-fold higher
      level of gamma-globin mRNA), while no increment of beta-globin was observed.

PMID- 7520034
TI  - Ultrastructural localization of epidermal growth factor (EGF)-receptor
      transcripts in the cell nucleus using pre-embedding in situ hybridization in
      combination with ultra-small gold probes and silver enhancement.
AB  - A high-resolution in situ hybridization method is described for localizing
      epidermal growth factor (EGF)-receptor transcripts in nuclei of A431 epidermoid
      carcinoma cells. The method is based upon the use of ultra-small gold particles
      in combination with silver enhancement. The RNA of the EGF-receptor was detected
      mainly around the nucleoli. After removal of the DNA using nucleases and high
      salt extraction, the RNA of the EGF-receptor appears to be associated with the
      nuclear matrix. The RNA of the EGF-receptor was observed in close contact with
      the SC-35 splicing protein, but no exact colocalization was observed. These
      results demonstrate that high resolution pre-embedding in situ hybridization in
      combination with immunocytochemistry, both using ultra-small gold as a detection
      method, provides a powerful tool to unravel the organization of nuclear
      processes.

PMID- 7520037
TI  - Nitric oxide synthase from rat colorectum: purification, peptide sequencing,
      partial PCR cloning, and immunohistochemistry.
AB  - Nitric oxide synthase (NOS) has been purified over 6,500-fold with a 3.4% yield
      from rat colorectum with 2',5'-ADP-Sepharose, DEAE cellulose, and gel filtration.
      The purified enzyme gave a single band corresponding to an apparent molecular
      mass of 160 Dka on sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      When assayed in the requisite presence of L-arginine, CaCl2, NADPH, calmodulin,
      tetrahydro-L-biopterin, and FAD, the purified enzyme exhibited a specific
      activity of 328 nmol/min/mg L-citrulline formed and an apparent Km for L-arginine
      of 2.9 microM. Amino acid sequencing of 12 peptides revealed identical sequences
      to that of the neuronal type enzyme except for two altered amino acid residues.
      When partial reverse transcription-polymerase chain reaction of RNA from rat
      colorectum and cerebellum was performed using primers designed according to the
      amino acid sequences determined, these amino acid changes were found in both cDNA
      fragments, indicating the identity of the colorectal enzyme to the cerebellar
      one. A polyclonal antibody raised against NOS purified from rat cerebellum cross
      reacted with the NOS from colorectum but not that from IFN-gamma stimulated
      macrophage-derived cells, RAW 264.7. Immunohistochemical analysis of the
      colorectum using this specific antibody indicated that Auerbach's plexus is
      strongly immunoreactive, supporting the hypothesis that NO is an inhibitory
      transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.

PMID- 7520038
TI  - Expression of recombinant mouse/human chimeric antibody specific to human GMP
      140/P-selectin.
AB  - To construct a mouse/human chimeric antibody, we cloned the genomic DNAs for Ig
      from a murine hybridoma that produces PL7-6 monoclonal antibody specific to human
      P-selectin and expressed them in SP2/0 myelomas using a series of pSV2 vectors.
      Transfected cells that produce the mouse/human chimeric anti-human P-selectin
      antibody were geneticin-selected and screened by an immunoassay using immobilized
      antigen. The chimeric antibody, cPL-2R1, expressed by the resultant clone has the
      murine Ig variable region and the human Ig constant region. The native antibody
      PL7-6 and the chimeric antibody cPL-2R1 react equally with purified P-selectin
      and thrombin-stimulated platelets. Competitive inhibition tests demonstrated that
      the native antibody PL7-6 and the chimeric antibody cPL-2R1 had identical
      affinity for purified human P-selectin. Thus, although human IgG1 constant region
      was substituted for the murine counterpart in this chimeric antibody, its
      specificity and binding affinity for P-selectin was not altered. This chimeric
      antibody may prove useful when employed in combination with imaging reagents or
      therapeutic drugs for targeting activated platelets or endothelium in patients
      with thrombosis or intravascular inflammation.

PMID- 7520039
TI  - The Caco-2 cell monolayer system as an in vitro model for studying bacterial
      enterocyte interactions and bacterial translocation.
AB  - Partly because of inherent limitations of in vivo models, the cellular mechanisms
      underlying the process of bacterial translocation across the intestinal
      epithelial barrier are incompletely understood. We therefore used the Caco-2
      intestinal cell line as an in vitro model to examine the bacterial translocation
      process under controlled conditions. Caco-2 cells were grown on porous membranes
      in the upper compartment of a two-compartment system. Caco-2 cells were cultured
      for 7, 14, 21, or 28 days. Cellular confluence and tight junction integrity were
      verified by measurements of dextran permeability and transepithelial electrical
      resistance. Bacterial translocation was measured by culturing the bacteria (E.
      coli C25) that were able to cross the Caco-2 cell monolayer. The passage of E.
      coli C-25 and dextran across the Caco-2 monolayer was higher and the
      transepithelial electrical resistance lower after 7 days of culture than after 14
      or 21 days of culture. The Caco-2 cells became impermeable to dextran blue after
      14 days of culture with an average transepithelial electrical resistance of 173.1
      +/- 9.24 ohms.cm2. When increasing doses of (10(2)-10(9) colony-forming units) of
      E. coli were tested in 14-day-old Caco-2 monolayers, bacterial translocation
      occurred in a time- and dose-dependent fashion. Once cellular confluence and
      tight junction integrity have been established, bacterial translocation across
      Caco-2 cells appears to be a time- and dose-dependent process.

PMID- 7520041
TI  - A 28 kDa sarcolemmal antigen in kidney principal cell basolateral membranes:
      relationship to orthogonal arrays and MIP26.
AB  - Two recently cloned water channels, CHIP28 and WCH-CD, are homologous to MIP26,
      an integral membrane channel-forming protein found in lens fiber plasma
      membranes. CHIP28 is found in basolateral and apical plasma membranes of kidney
      proximal tubules and thin descending limbs of Henle, whereas WCH-CD is apically
      located in collecting duct principal cells. So far, the putative water channel
      that may be responsible for the high constitutive permeability of principal cell
      basolateral membranes has not been identified. Interestingly, freeze-fracture
      electron microscopy has shown that characteristic orthogonal arrays of
      intramembrane particles (OAPs) are found on the basolateral plasma membranes of
      collecting duct principal cells, and that morphologically identical OAPs present
      in lens fiber cell plasma membranes contain the protein MIP26. Similar OAPs have
      also been detected on plasma membranes of other cell types including gastric
      parietal cells, astroglial cells and skeletal muscle fibers. By indirect
      immunofluorescence, western blotting and northern blotting, MIP26 was found only
      in lens fibers. In addition, functional studies on reconstituted and oocyte
      expressed MIP26 excluded the possibility that MIP26 might be a basolateral water
      channel in the kidney. However, a polyclonal antibody raised against skeletal
      muscle sarcolemmal vesicles, which are enriched in OAPs, produced an intense
      staining of principal cell basolateral plasma membranes in kidney collecting duct
      and immunoprecipitated a 28 kDa protein from kidney papilla. The
      immunoprecipitated protein from papilla was not recognized by anti-CHIP28 or anti
      MIP26 antibodies, indicating that principal cell basolateral membranes contain a
      novel member of the CHIP/MIP family. Because this antibody also stained brain
      astrocyte end feet, which are enriched in OAPs, it is possible that the 28 kDa
      protein is related to these structures. We conclude that OAPs probably contain
      related but distinct proteins that may have different membrane channel functions
      in different cell types.

PMID- 7520043
TI  - Nuclear export of signal recognition particle RNA is a facilitated process that
      involves the Alu sequence domain.
AB  - The signal recognition particle is a cytoplasmic RNA-protein complex that
      mediates translocation of secretory polypeptides into the endoplasmic reticulum.
      We have used a Xenopus oocyte microinjection assay to determine how signal
      recognition particle (SRP) RNA is exported from the nucleus. Following nuclear
      injection, SRP RNA accumulated in the cytoplasm while cytoplasmically injected
      SRP RNA did not enter the nucleus. Cytoplasmic accumulation of SRP RNA was an
      apparently facilitated process dependent on limiting trans-acting factors, since
      nuclear export exhibited saturation kinetics and was completely blocked either at
      low temperature or by wheat germ agglutinin, a known inhibitor of nuclear pore
      mediated transport. At least one target for trans-acting factors that promote
      nuclear export of SRP RNA appears to be the Alu element of the molecule, since a
      transcript consisting of only the Alu sequence was exported from the nucleus in a
      temperature-dependent manner and the Alu transcript competed in the nucleus for
      transport with intact SRP RNA. Although the identities of trans-acting factors
      responsible for SRP RNA transport are at present unknown, we suggest that
      proteins contained within the cytoplasmic form of SRP are candidates. Consistent
      with this idea were the effects of a mutation in SRP RNA that prevented binding
      of two known SRP proteins to the Alu sequence.

PMID- 7520042
TI  - Mutations in the non-helical linker segment L1-2 of keratin 5 in patients with
      Weber-Cockayne epidermolysis bullosa simplex.
AB  - Keratins are the major structural proteins of the epidermis. Analyzing keratin
      gene sequences, appreciating the switch in keratin gene expression that takes
      place as epidermal cells commit to terminally differentiate, and elucidating how
      keratins assemble into 10 nm filaments, have provided the foundation that has led
      to the discoveries of the genetic bases of two major classes of human skin
      diseases, epidermolysis bullosa simplex (EBS) and epidermolytic hyperkeratosis
      (EH). These diseases involve point mutations in either the basal epidermal
      keratin pair, K5 and K14 (EBS), or the suprabasal pair, K1 and K10 (EH). In
      severe cases of EBS and EH, mutations are found in the highly conserved ends of
      the alpha-helical rod domain, regions that, by random mutagenesis, had already
      been found to be important for 10 nm filament assembly. In order to identify
      regions of the keratin polypeptides that might be more subtly involved in 10 nm
      filament assembly and to explore the diversity in mutations within milder cases
      of these diseases, we have focused on Weber-Cockayne EBS, where mild blistering
      occurs primarily on the hands and feet in response to mechanical stress. In this
      report, we show that affected members of two different W-C EBS families have
      point mutations within 1 residue of each other in the non-helical linker segment
      of the K5 polypeptide. Genetic linkage analyses, the absence of this mutation in
      > 150 wild-type alleles and filament assembly studies suggest that these
      mutations are responsible for the W-C EBS phenotype. These findings provide the
      best evidence to date that the non-helical linker region in the middle of the
      keratin polypeptides plays a subtle but significant role in intermediate filament
      structure and/or intermediate filament cytoskeletal architecture.

PMID- 7520040
TI  - Laminin and tenascin assembly and expression regulate HC11 mouse mammary cell
      differentiation.
AB  - HC11 is a normal mouse mammary epithelial cell line that requires certain growth
      factors, such as EGF or bFGF, to respond optimally to lactogenic hormones and
      produce the differentiation marker beta-casein. Growth in insulin (Ins) or PDGF
      does not produce cells competent to respond to lactogenic hormones. Here we show
      that competency for differentiation is due at least in part to the modulation of
      extracellular matrix components. In particular we have studied laminin and
      tenascin. EGF alters endogenous laminin assembly. In addition, promotion of
      competency can be partially mimicked by plating HC11 cells on the E8 laminin
      fragment, which is able to induce lactogenic responsiveness in cells grown in the
      absence of EGF or bFGF. The production and assembly of tenascin is also dependent
      upon the growth conditions of the HC11 cells. EGF- or bFGF-grown competent cells
      produce tenascin but do not assemble it at the extracellular matrix as
      efficiently as Ins- or PDGF-grown, non-competent cells. This alteration
      apparently leads to a change in the cellular microenvironment that supports beta
      casein production. In addition, when competent cells are plated on dishes coated
      with tenascin, lactogenic hormone induction of beta-casein is inhibited. The data
      suggest that tenascin assembly and beta-casein production are opposing features
      of a coordinated differentiation program of HC11 cells.

PMID- 7520044
TI  - Cellular localization of RNA14p and RNA15p, two yeast proteins involved in mRNA
      stability.
AB  - RNA14 and RNA15 were originally identified by temperature-sensitive mutations
      that cause a rapid decrease in poly(A)-tail length and overall mRNA levels at the
      restrictive temperature. We have raised antibodies to the RNA14 and RNA15
      proteins, and used subcellular fractionation and immunofluorescence to localize
      these proteins within the yeast cell. RNA14p is a 73 kDa protein found in both
      the nucleus and the cytoplasm, whilst RNA15p is a 42 kDa protein detected only in
      the nucleus. The observation that both proteins are found in the nucleus is in
      agreement with previous genetic data which suggest an interaction between RNA14p
      and RNA15p. Also the joint nuclear localization is consistent with the
      biochemical data suggesting a role in polyadenylation. The detection of
      significant amounts of RNA14p in the cytoplasm opens the possibility of a second
      function for this protein, either in cytoplasmic regulation of mRNA deadenylation
      or, more interestingly, in mRNA stability.

PMID- 7520045
TI  - Conformation dependence of integrin-type II collagen binding. Inability of
      collagen peptides to support alpha 2 beta 1 binding, and mediation of adhesion to
      denatured collagen by a novel alpha 5 beta 1-fibronectin bridge.
AB  - The mechanism of interaction of chondrocytic cells with cartilage-specific type
      II collagen has been examined using HCS-2/8 human chondrosarcoma cells as a model
      system. By the criteria of specific collagen secretion and integrin expression
      profile, HCS-2/8 have a similar differentiated phenotype to normal chondrocytes
      and are therefore a good model system. HCS-2/8 cells were able to attach and
      spread on both native and heat-denatured pepsinised type II collagen, and assays
      using denatured cyanogen bromide fragments apparently localised the major cell
      binding site to the CB10 fragment. However, when they were used as soluble
      inhibitors, cyanogen bromide fragments were found to block adhesion to denatured
      collagen, but had no effect on either attachment or spreading on the native
      molecule. The inability of cyanogen bromide fragments to reproduce the cell
      binding site of native collagen demonstrated a strict dependence on collagen
      conformation. This was also reflected in the receptors that were employed by HCS
      2/8 cells for binding to type II collagen: binding to native collagen was
      mediated by the integrin alpha 2 beta 1 while binding to denatured collagen was
      mediated by a novel alpha 5 beta 1-fibronectin bridge. The identification of this
      bridge adds to the mechanisms by which cells can bind to denatured collagens. The
      previously characterised KDGEA active site peptide from type I collagen was found
      to be inactive as an inhibitor of type II collagen-mediated adhesion. The
      implications of these findings for the strategies used to identify adhesive
      active sites within collagens are discussed. In particular, these data suggest
      that, unlike other integrin ligands, a synthetic peptide-based approach is not
      suitable for the identification of collagen active sites.

PMID- 7520046
TI  - Thrombocytopenia in the HIV-infected patient.
AB  - Autoimmune thrombocytopenia occurs in 15% to 20% of patients with HIV infection.
      When prednisone fails, the conventional choice is splenectomy. When splenectomy
      fails, other options, established and investigational, still exist.

PMID- 7520047
TI  - Rapid cytokeratin stains enhance the sensitivity of Mohs micrographic surgery for
      squamous cell carcinoma.
AB  - BACKGROUND: Recurrence of squamous cell carcinoma (SCC) following Mohs
      micrographic surgery is uncommon. However, such cases do exist, presumably
      because of incomplete excision. Identification of single cells or small clumps of
      SCC tumor may be extremely difficult and can be compromised by inflammatory
      reaction. OBJECTIVE: The purpose of this study was to evaluate the benefits of
      incorporating rapid cytokeratin (CK) stains into Mohs technique. METHODS: Simple
      modification of standard immunoenzyme techniques allows keratin-specific staining
      to be achieved in less than 90 minutes on Mohs cryostat sections. We used the
      rapid labeled streptavidin biotin anticytokeratin method at the stage when no
      tumor was apparent by hematoxylin and eosin staining in 20 patients with large,
      aggressive, or recurrent invasive SCCs. RESULTS: In eight cases, single cells or
      small clumps of SCC tumor were identified utilizing AE-1 monoclonal antibody.
      These patients subsequently underwent further surgery, including wider tumor
      resection, superficial parotidectomy, or postoperative radiation therapy.
      CONCLUSION: The rapid CK antibody staining technique enhances the sensitivity of
      tumor identification in Mohs micrographic surgery, and should reduce tumor
      recurrence rates.

PMID- 7520048
TI  - Primary subcutaneous leiomyosarcoma exhibiting the characteristic immunophenotype
      positive for vimentin and desmin.
AB  - BACKGROUND: Primary subcutaneous leiomyosarcoma is a rare neoplasm composed of
      plump, elongated spindle cells arranged in interweaving fascicles. OBJECTIVE:
      Differential diagnosis might be facilitated by the use of immunohistochemistry.
      METHODS: A case of subcutaneous leiomyosarcoma was investigated histologically on
      paraffin-embedded tissue and immunohistochemistry was performed following
      standard procedures. RESULTS: The case reported exhibited light microscopic
      features and an immunophenotype characteristic of leiomyosarcoma. However, the
      intermediate filament desmin could only be found on a small number of tumor
      cells. CONCLUSION: Expression of these markers might vary considerably and
      immunoperoxidase stainings need to be carefully evaluated. Utilization of several
      antibodies directed against different desmin epitopes might be advantageous.

PMID- 7520049
TI  - Who is in control? An investigation of nurse and patient beliefs relating to
      control of their health care.
AB  - This study compares nurse and patient beliefs regarding control of health and
      perceptions of the amount of patient control. Data were collected from 21 nurses
      and 32 patients on a mixed surgical ward, using a series of self-report
      questionnaires. No difference was found between nurse and patient perceptions of
      patient control. However, nurses were found to have a significantly greater
      desire for control over their own health care and a significantly weaker belief
      in the influence of powerful others (i.e. doctors and nurses) than did patients.
      It is suggested that such differences in nurse and patient beliefs will have
      significant effects on how nurses and patients feel about the care patients
      receive. Implications of the findings for nursing theory and nurse education are
      also considered. In the light of previous research showing the stress-reducing
      effects of giving control to patients who want and expect it, the study calls for
      the development of a tool to assess the amount of control desired by each
      patient. This should help to ensure that nursing care is congruent with the
      control beliefs of the patient, rather than those of the nurse.

PMID- 7520050
TI  - Presence of growth factors in palmar and plantar fibromatoses.
AB  - Palmar and plantar fibromatoses are disease processes in which the presence of
      certain growth factors has not been defined. Monoclonal antibodies against
      transforming growth factor-beta, epidermal growth factor, procollagen type 1,
      fibronectin, phosphotyrosine residues, and CD41 platelet antigen were used in
      standard immunoperoxidase staining to study 36 nodules and 24 cords obtained from
      patients with fibromatoses. The specimens were studied via light microscopy, and
      staining intensity was quantitated using a computer-enhanced video system.
      Transforming growth factor-beta staining paralleled procollagen I, fibronectin,
      and phosphotyrosine staining within the nodule (early stages) but not the cord
      (late stages) tissue. These factors showed significant increased staining in the
      early stage of fibromatosis when compared to the late stage. This study is a
      preliminary demonstration of the presence of transforming growth factor-beta in
      palmar and plantar fibromatoses.

PMID- 7520051
TI  - Intraepithelial lymphocytes and their recognition of non-classical MHC molecules.
AB  - Recent studies of the TCR alpha and beta chains expressed by normal human IELs
      suggest that these intestinal lymphocytes are directed at a limited set of
      antigens, presumably on intestinal epithelial cells in view of their anatomic
      location. The direct sequence analysis of these cells has indicated that they are
      oligoclonal and cannot, therefore, be responding to the complex mixture of
      antigens which are present in the lumen. The abundant expression of the CD8
      accessory molecule by the IELs, in addition, indicates that these putative
      intestinal epithelial cell antigens are presented by MHC class I or I-like
      molecules. The expression of CD8 also suggests that these cells function
      biologically in part as cytolytic T lymphocytes which is consistent with a
      variety of functional studies. Taken together with their expression of the CD45RO
      isoform, these phenotypic and functional observations suggest that iIELs are
      cytolytic, memory cells which are responsive to an extremely limited number of
      antigens bound to major histocompatibility complex (MHC) class I or class I-like
      molecules. Several non-polymorphic MHC class I-like molecules such as Qa, the
      thymus leukemia antigen (TL) and CD1 in the mouse and CD1 in human represent
      important candidate ligands for these oligoclonal iIELs. TL and CD1 are expressed
      specifically by murine intestinal epithelial cells. In humans, CD1d is
      constitutively expressed by intestinal epithelial cells. In addition, we have
      isolated iIEL T cell clones which specifically recognize members of the CD1 gene
      family when expressed on a transfected B cell line that lacks HLA-A and B and
      have shown that the proliferation of peripheral blood T cells to intestinal
      epithelial cells is CD1d dependent. Thus, the evidence to date strongly implicate
      the nonpolymorphic, class Ib molecules as novel restriction elements for unique
      populations of lymphocytes within the intestinal epithelium.

PMID- 7520052
TI  - Effect of bleomycin-induced fibrosis on pulmonary metabolism of selected
      xenobiotics.
AB  - Few studies are available characterizing the effects of fibrosis on pulmonary
      disposition of drugs or environmental pollutants. Two model substrates, p
      nitroanisole and carbofuran, were selected to evaluate the effect of bleomycin
      induced fibrosis on pulmonary disposition and metabolism using the isolated
      perfused lung and in vitro enzyme preparations. The rate of p-nitroanisole
      oxidation in the isolated perfused lung was significantly lower in fibrotic (k =
      0.0334 min-1) than in control (k = 0.0493 min-1) lungs. However, there was no
      difference in the amount of p-nitrophenol formed between control (38 +/- 4
      micrograms) and fibrotic (47 +/- 7 micrograms) lungs. Carbofuran clearance was
      similar in control (t1/2 = 91 min, ke = 0.008 min-1) and fibrotic (t1/2 = 75 min,
      ke = 0.009 min-1) lungs and was consistent with a one-compartment model. The Km
      value for p-nitrophenol formation in microsomes (0.185 +/- 0.095 mM) from control
      lungs was similar to fibrotic lungs (0.054 +/- 0.014 mM); however, Vmax was
      significantly higher in healthy (34.6 +/- 6.3 pmoles/min per mg microsomal
      protein) than in fibrotic (11.16 +/- 3.19 pmoles/min per mg microsomal protein)
      lungs. In vitro carbofuran studies indicated limited metabolism of carbofuran in
      both healthy and fibrotic microsomal enzyme preparations (< 5% of the
      administered dose). Lower p-nitroanisole metabolism in fibrotic lungs was
      consistent with lower levels of cytochrome P-450 2B1/B2 measured in bleomycin
      treated lungs. Results suggest that individuals with bleomycin-induced pulmonary
      fibrosis may be at greater risk when exposed to certain toxic environmental
      chemicals or drugs that require detoxification by pulmonary microsomal enzymes.

PMID- 7520053
TI  - Terazosin in the treatment of hypertension and symptomatic benign prostatic
      hyperplasia: a primary care trial.
AB  - BACKGROUND: Terazosin, an alpha 1 blocker initially used as an antihypertensive,
      was approved in 1993 for use in the treatment of benign prostatic hyperplasia
      (BPH) symptoms. This study was designed to determine the safety and efficacy of
      terazosin in treating patients with concomitant BPH and hypertension. METHODS:
      Middle-aged men with essential hypertension were enrolled by their primary care
      physicians in community practice. Those with symptoms of benign prostatic
      hyperplasia were identified by a Boyarsky scale score. The study was a 12-week,
      dose-escalation, open-label protocol for men aged 45 years and older. RESULTS:
      Enrollment in the study totaled 5365 patients. Of these, 1483 had Boyarsky scores
      of > or = 7, indicating symptomatic BPH. All patients with elevated blood
      pressure at the beginning of the study, including those with symptomatic BPH,
      showed significant reduction in blood pressure at the end of the 12-week trial.
      The patients with symptomatic BPH had statistically significant improvement in
      their BPH voiding symptoms. In the 1483 patients with BPH symptoms, terazosin
      produced a mean reduction of 55% in overall Boyarsky scores, 57% in obstructive
      symptom scores, and 54% in irritative symptom scores. In patients with baseline
      blood pressure < or = 150/90 mm Hg, blood pressure reductions were statistically
      significant but clinically irrelevant. Adverse events were mild. CONCLUSIONS:
      Terazosin is safe and effective in treating concomitant hypertension and BPH.

PMID- 7520054
TI  - Tissue-specific expression of calbindin-D28K gene during ontogeny of the chicken.
AB  - The vitamin D3-dependent calcium binding protein, calbindin-D28K (CaBP-D28K),
      plays an important role in transepithelial calcium translocation. To evaluate its
      role in chick embryonic calcium metabolism, steady-state levels of CaBP-D28K mRNA
      in various tissues of the chick embryo were determined by Northern blot and slot
      blot analyses, and CaBP-D28K concentrations in the examined tissues and plasma
      were estimated by RIA. High levels of CaBP-D28K mRNA were found in the embryonic
      kidney (mesonephros) on embryonic day (E) 10 and E12 and thereafter gradually
      decreased until hatching. CaBP-D28K mRNA levels were low in the yolk sac until
      E16 but increased on E18 and reached a maximum on E20. A steady increase in CaBP
      D28K mRNA levels was observed in the cerebellum during the development from E10
      to post-hatching. CaBP-D28K mRNA levels in the intestine were very low during the
      incubation period but significantly increased on days 1 and 7 after hatching. By
      Northern blot analysis, CaBP-D28K mRNA was barely detectable in liver, heart, and
      chorioallantoic membrane of the embryonic chick. Changes in immunoreactive CaBP
      D28K of each tissue paralleled observed changes in mRNA levels. In plasma,
      measurable levels of CaBP-D28K were found as early as E8 and were stable until
      E18, when 6.5-fold increase was observed compared to E16. The highest level of
      CaBP-D28K in plasma was found on E20 and decreased after hatching. These temporal
      profiles of CaBP-D28K suggest that it may play an important role in the
      regulation of chick embryonic calcium homeostasis.

PMID- 7520055
TI  - Evidence in support of a role for Ca(2+)-activated K+ channels in the hamster
      sperm acrosome reaction.
AB  - The sperm acrosome reaction (AR) is a crucial step for mammalian fertilization.
      This work describes experiments to test the effect of the cesium ion (Cs+) and
      charybdotoxin (ChTX) on the Ca2+ or Na+/K+ ionophores stimulated hamster sperm AR
      in vitro. Cs+ and ChTX, a polypeptide toxin from the venom of the scorpion Leirus
      quinquestriatus, are considered blockers of Ca(2+)-activated K+ channels in
      several somatic cells. Both agents inhibited the AR by 55-66%. The inhibition was
      completely reversed by the Na+/K+ ionophore nigericin, but not by the Ca2+
      ionophore A-23187. Results give evidence in support of a role for Ca(2+)
      activated K+ channels in K+ influx required for the occurrence of the hamster
      sperm acrosome reaction.

PMID- 7520056
TI  - Congenital insensitivity to pain: a 20 year follow up.
AB  - The exact nosological status of "congenital insensitivity to pain" remains in
      doubt. Possible pathological correlates of this clinical syndrome include sensory
      neuropathy, central lesions at the level of the reticular formation or dorsal
      horn of the spinal cord, or a central indifference to, or asymbolia for, pain.
      The reassessment of two members of a kindred previously reported more than 20
      years ago as having congenital insensitivity to pain indicated that they in fact
      had an inherited sensory and autonomic neuropathy. Prolonged follow up and
      morphometric analysis of sequential nerve biopsies may be necessary to
      definitively establish this diagnosis.

PMID- 7520057
TI  - Absence of Epstein-Barr virus RNA in multiple sclerosis as assessed by in situ
      hybridisation.
AB  - Epidemiological and serological evidence has suggested a role for Epstein-Barr
      virus infection in the aetiology of multiple sclerosis. Epstein-Barr virus
      specific RNA was looked for in the brains of 10 patients with multiple sclerosis
      by in situ hybridisation. A total of 21 plaques was examined. In all of these
      preservation of RNA was shown by hybridisation of control probes to mitochondrial
      rRNA but no signal was detected with the Epstein-Barr virus probes. It is
      unlikely that persistent or latent Epstein-Barr virus infection of the CNS occurs
      in multiple sclerosis, although present findings do not exclude a role for
      Epstein-Barr virus in the initiation of this disorder.

PMID- 7520060
TI  - Reliability of clinical examination in the diagnosis of parotid tumours.
AB  - This study included 128 superficial lobe parotid tumours seen over a 27-year
      period. Using data stored in a prospective manner the sensitivity and specificity
      of regarding every lump in the tail of the parotid as being either a pleomorphic
      adenoma or other benign tumour was assessed. We found that 71% of all lumps in
      the tail of the parotid with no facial palsy were pleomorphic adenomas,
      sensitivity 0.88 and specificity 0.50. We also found that 96% of lumps in the
      tail of the parotid with no facial palsy, pain, trismus or fixation were benign,
      sensitivity 0.91 and specificity 0.84. We feel this information is useful in
      managing elderly patients and those reluctant to undergo surgery. It provides
      additional evidence as to the nature of the tumour and can be considered with the
      results of fine needle aspiration cytology (if available).

PMID- 7520058
TI  - High dose chemotherapy with stem-cell transplantation in a metastatic
      medulloblastoma in an adult: a case report and review of the literature.
AB  - Medulloblastoma is a rare tumor in adult. High doses of megavoltage irradiation
      of the posterior fossa have been resulted in a better survival (48 to 78% at 5
      years) of the patient. It is sensitive to a wide variety of chemotherapy drugs,
      but adjuvant chemotherapy has not been proved effective in adults although data
      are limited. We report the case of a cerebellar medulloblastoma with bony and
      medullar metastases. High-dose chemotherapy with peripheral stem-cell
      transplantation was performed while the patient was in remission following
      conventional chemotherapy. Complete remission lasted for 8 months. This
      therapeutic approach of metastatic medulloblastoma might be of value as this
      tumor is chemosensitive and not cured by conventional treatment. Internal
      radiotherapy by Samarium-153 was also carried out and proved to be an effective
      palliative treatment of pain.

PMID- 7520059
TI  - Inactivation of outward Na(+)-Ca2+ exchange current in guinea-pig ventricular
      myocytes.
AB  - 1. Outward Na(+)-Ca2+ exchange currents were measured in freshly dissociated
      guinea-pig myocytes to probe in intact cells the functional status of exchanger
      inactivation reactions, described previously in giant excised cardiac membranes
      patches. 2. When the cytoplasmic (pipette) solution contained 40 mM Na+ and 0.1
      microM free Ca2+ (50 mM EGTA), the outward exchange current activated by
      extracellular Ca2+ decayed with time (time constant, 13.1 +/- 2.6 s; n = 6), and
      an inward current transient was observed upon removal of extracellular Ca2+. Both
      the current decay and the subsequent inward current transient were remarkably
      diminished with a saturating (100 mM) pipette Na+ concentration. 3. With 100 mM
      cytoplasmic Na+ and 140 mM extracellular Na+, a significant fraction of the
      exchanger population is predicted to be in an inactive state. Intracellular
      application of 2 mg ml-1 chymotrypsin and 5 microM sodium tetradecylsulphate,
      both of which decrease Na(+)-dependent inactivation in giant membrane patches,
      increased the outward exchange current by about 160-170%, suggesting that about
      60-70% of exchangers might be inactivated. 4. With 100 mM cytoplasmic Na+ and no
      extracellular Na+ (replaced with 140 mM Li+), application of extracellular Ca+
      was predicted to reorient exchanger binding sites from the extracellular side to
      the cytoplasmic side and thereby favour inactivation. During such protocols, the
      outward exchange current decayed by 60-80% when activated by extracellular Ca2+.
      The current decayed similarly when extracellular Ca2+ and Na+ were applied
      together, whereby current magnitudes were about 3-fold smaller. 5. The decay of
      outward exchange current usually followed a biexponential time course (5.8 +/-
      3.5 and 27.3 +/- 16.3 s, means +/- S.D., n = 11). Intracellular application of
      0.5-2 mg ml-1 trypsin attenuated the fast component more than the slow component,
      suggesting that the fast component reflects an inactivation process. 6. Current
      voltage (I-V) relations of the outward exchange current became less steep during
      the inactivation protocols, but this flattening could not be correlated with
      inactivation. 7. Replacement of extracellular Li+ with N-methyl-D-glucamine
      (NMG), tetraethylammonium (TEA), sucrose or Cs+ resulted in a flattening of I-V
      relations and a decrease of the outward exchange current amplitude by
      approximately 3-fold, but the kinetics and extent of inactivation were not
      remarkably changed. Thus, the mechanism of inactivation appears to be independent
      of the mechanism(s) of activation by extracellular monovalent cations.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7520061
TI  - General practitioner referral of patients with symptoms of peripheral vascular
      disease.
AB  - A questionnaire survey has been carried out to assess the circumstances under
      which general practitioners refer patients with peripheral vascular disease to a
      district general hospital. A single-page questionnaire was sent to 100 general
      practitioners seeking information about their referral of patients with
      claudication, ischaemic rest pain or abdominal aortic aneurysms. Of the 77% who
      responded, over half would not refer a 70-year-old with claudication at half a
      mile or an 80-year-old with claudication at 100 m, and 44% would not refer an 80
      year-old with a palpable abdominal aortic aneurysm. The results suggest that many
      elderly patients with symptomatic claudication or asymptomatic aneurysms are not
      currently referred. Changing referral patterns due to a heightened awareness of
      minimally invasive methods of treatment or the benefits of aneurysm surgery have
      the potential for profound effects upon vascular surgical work-load.

PMID- 7520062
TI  - Incidence of carcinoma in multinodular goitre in Saudi Arabia.
AB  - Over a period of 3 years, 614 patients were admitted to the General Surgery
      Department at the Riyadh Central Hospital with thyroid enlargements. Based on the
      clinical examination and non-invasive investigations, the thyroid swellings were
      classified into solitary nodule (45%), multinodular (44%) and diffuse goitre
      (11%). Subsequent classification of the goitres on the basis of intraoperative
      findings and histopathological examination revealed increase in the number of
      multinodular goitres to 70% while the solitary nodule and diffuse goitres dropped
      to 24% and 6%, respectively. Malignant changes were seen in 10% of the
      multinodular goitres after pathological examination. 75% of the carcinomas seen
      in multinodular goitres were of the papillary type. In almost none of the cases,
      it was possible to discover the malignancy preoperatively. The study recommends
      surgical intervention in all nodules goitres irrespective of being solitary or
      multinodular.

PMID- 7520064
TI  - Graded exercises for basic training in laparoscopic surgery.
AB  - A series of graded exercises for use in laparoscopic simulation is described.
      These exercises are designed to introduce the basic skills required for
      laparoscopic surgery, and have been found to be useful both for the training of
      junior surgeons and in workshops.

PMID- 7520063
TI  - Basal cell carcinomas: do they need to be followed up?
AB  - Basal cell carcinoma (BCC) is the commonest of the malignant skin tumours. The
      follow-up of patients following excision of these lesions varies immensely. The
      aim of this study was to assess the need for outpatient follow-up of patients who
      had a primary BCC excised. A retrospective study was performed using the case
      notes of 206 patients who had a primary BCC excised in Bangour General Hospital
      in the years 1986 and 1987. Fourteen were excluded from the study, leaving 192
      patients with 215 lesions. The overall recurrence rate was 5.1% with 39% of
      lesions recurring if the tumour was incompletely excised compared with 1% if it
      was excised completely. Complete excision is therefore the key to surgical
      control and we feel that there is no need to follow up patients routinely if the
      BCC has been completely excised.

PMID- 7520065
TI  - A safe percutaneous procedure for trigger finger release.
AB  - A safe and easily performed method for percutaneous release of trigger digits is
      described which is performed in the outpatient clinic within a few minutes,
      without requiring any special instrument. Results in terms of abolishing
      triggering immediately and patient acceptance are excellent. No important
      complications have been observed in our first 38 procedures.

PMID- 7520066
TI  - Absent portal vein presenting as rectal bleeding: a case report.

PMID- 7520068
TI  - Respiratory arrest during an orthodontic impression of a cleft palate, in a baby
      with Brachmann-de Lange syndrome.

PMID- 7520067
TI  - Pelvic appendicitis in young adult males masquerading as cystitis.

PMID- 7520069
TI  - Audit of ankle fracture fixation in the elderly.
AB  - To assess the results of operative treatment of ankle fractures in the elderly,
      we have reviewed the results of ankle fracture fixation in 76 patients aged over
      50 years. This was carried out with special reference to the early complications.
      Our series had a 1.8% incidence of infection and a 5.2% incidence of delayed
      healing and wound necrosis. Malunion occurred in 7.9% of patients, and was due in
      all cases to either imperfect peroperative reduction or inadequate fixation. In
      no case did fixation fail because of poor bone quality. We conclude that internal
      fixation of ankle fractures in the elderly carries acceptable risks, so long as
      careful attention is paid to surgical technique, and fixation is in accordance
      with AO/ASIF principles.

PMID- 7520070
TI  - The collateral ligament flexion-extension test (CLEFT) in total knee replacement.
AB  - We present a simple preoperative clinical test, the collateral ligament extension
      flexion test (CLEFT). In patients undergoing total knee arthroplasty, with a
      preoperative valgus or varus deformity, this test establishes which knees have
      balanced collateral ligaments. It predicts which knees will not require soft
      tissue adjustment during the course of their surgery despite, in some cases,
      large deformities. The mechanism of the test is based on the observation that, in
      certain patients, a deformity present in extension is seen to correct in flexion.
      The sensitivity of this observation was checked in 44 consecutive patients
      undergoing total knee arthroplasty, and who had either a valgus or varus
      deformity in extension greater than 10 degrees. In 34 patients the test was
      positive, and none of these required ipsilateral collateral ligament release. All
      of the 10 patients with a negative test required soft tissue adjustment. In
      patients undergoing unconstrained total knee arthroplasty this test is reliably
      predictive of those knees with preoperative deformity which can be corrected
      simply by correctly aligned bone cuts. It supports the principle of bony
      resection prior to soft tissue adjustment in this form of surgery.

PMID- 7520071
TI  - Cancellous screw fixation for subcapital femoral neck fractures.
AB  - Experience in treating 80 subcapital femoral neck fractures by AO/ASIF cancellous
      screws is reported. Immediate full-weight bearing was allowed routinely. The mean
      follow-up was 28 months. Non-union occurred in 2% and late segmental collapse in
      12% of patients with undisplaced fractures. Non-union occurred in 16.7% and late
      segmental collapse in 30% of patients for displaced fractures. Regression of
      screws occurred in 30% of patients, all of which were detected within the first
      month after the operation. It was associated with a significantly higher risk of
      non-union and late segmental collapse for both undisplaced (P < 0.01) and
      displaced (P < 0.001) fractures.

PMID- 7520072
TI  - An early caesarean operation (1800) performed by John and Charles Bell.
AB  - An articulated skeleton in the Bell Collection in the Museum of the Edinburgh
      College of Surgeons is of a woman who died shortly after a Caesarean section,
      believed to be the 18th recorded case of such an operation performed in the UK
      and Ireland. The fact that John and Charles Bell were the surgeons involved is of
      particular interest, due to their importance in the practice of surgery and
      surgical anatomy in Edinburgh during the early part of the 19th century. The
      woman had a restricted pelvic inlet and outlet resulting from puerperal
      osteomalacia, the commonest indication for carrying out this operation during the
      18th and 19th centuries. Evidence from the examination of contemporary parish
      baptism and burial records, as well as meteorological records, established that
      the Caesarean operation was performed on 29 January 1800. The surviving child was
      subsequently baptized 'Caesar', in accordance with the common practice at that
      time.

PMID- 7520073
TI  - Soft tissue facial injuries in sport (excluding the eye).
AB  - Facial injuries in sport have until recently received little publicity.
      Certainly, compared to other forms of injury, particularly orthopaedic, they seem
      neither to occur as frequently nor to have the same significance in relationship
      to complications, resulting in time off the sport, or long-term problems.
      Obtaining figures relating to the frequency of facial injuries in different
      sports is not easy because they are often trivial or considered so to be. Record
      keeping by club staff can be erratic to say the least and many injuries do not
      reach hospitals. Increased interest in facial injuries is occurring as a result
      of a number of factors, including fears regarding transfer of blood-spread
      infections in contact sports and the increasing aggression occurring in some
      sports resulting in injuries to players, officials, and supporters during or even
      after the event. Possible reasons for this are discussed, as will be the
      implications.

PMID- 7520074
TI  - Intermittent claudication due to spinal stenosis in a vascular surgical practice.
AB  - Intermittent claudication can be due to spinal canal stenosis. In order to define
      the frequency with which this condition presents to a vascular surgeon a review
      of 271 patients referred with claudication was carried out. Twenty-one (8%) were
      ultimately diagnosed as having spinal stenosis. There were no significant
      differences with regard to age or sex between these patients and those with true
      vascular claudication. There was, however, a significantly lower number of
      smokers in the spinal stenosis group. When the presenting features of the spinal
      stenosis group were analysed 62% (13/21) reported sensory symptoms such as
      numbness or parasthesiae, 38% (8/21) back pain and 67% (14/21) true pain in the
      legs on walking. In 71% (15/21), symptoms were reported as being bilateral and
      29% (6/21) had reduced Doppler pressures. It is stressed that vascular surgeons
      need to maintain a high index of suspicion for spinal stenosis especially as the
      condition may coexist with vascular disease, making diagnosis difficult.

PMID- 7520075
TI  - CRP levels as a measure of surgical trauma: a comparison of different general
      surgical procedures.
AB  - Acute phase proteins are released into the circulation as part of the metabolic
      response to trauma. C reactive protein (CRP) has been shown to be the most
      specific and sensitive indicator of trauma. We measured pre- and postoperative
      CRP levels in patients undergoing varicose vein surgery, inguinal herniorrhaphy,
      laparoscopic cholecystectomy and open cholecystectomy. A significant difference
      is shown between the levels found in those undergoing varicose vein, hernia
      surgery or open cholecystectomy; however, there is no significant difference in
      the CRP levels between open and laparoscopic cholecystectomy.

PMID- 7520076
TI  - Light reflection rheography: a simple method of assessing lower limb venous
      filling.
AB  - Light reflection rheography (LRR) has been developed as a simple, quick and non
      invasive test of venous function which reproduces the haemodynamic parameters of
      venous pressure measurements by recording changes in dermal blood content of the
      lower limb during exercise. It uses the same principles as photoplethysmography
      (PPG) but is simpler to use in a clinical context. To assess the comparability of
      LRR, changes in ambulatory venous pressure measurements were compared to
      simultaneous recordings of LRR in 40 limbs of 20 individuals with venous stasis
      during and after a standard exercise. One hundred and twenty paired observations
      were made with an excellent correlation between venous refill times (VRT)
      recorded by the two methods (r = 0.85, P < 0.01). There was no significant
      correlation between exercise induced changes in venous pressure (delta P) and
      light reflection (delta LR) as measures of venous emptying. LRR also demonstrated
      differences in VRT and delta LR of the limbs of normal subjects and those with
      signs of venous stasis (varicose veins) (P < 0.0001). Light reflection rheography
      is thus a simple accurate test of venous function which may be of value in both
      the pre- and postoperative assessment of venous function.

PMID- 7520077
TI  - An 11-year experience of arterial embolectomy in a district general hospital.
AB  - We present a retrospective audit of all arterial embolectomies performed at the
      East Glamorgan General Hospital over an 11-year period (1980-1990). Eighty-seven
      patients (47M:40F), mean age 67 years (50-90 years) underwent 95 embolectomies,
      an incidence consistent with previous studies. There were 17 upper and 71 lower
      limb emboli with a mean delay before diagnosis of 29 h (range 1-264 h). In 66% of
      cases the cause was atrial fibrillation; 33% received immediate heparinization
      and 14% prophylactic antibiotics. Surgery was performed by a consultant in 12 and
      registrars in 75 cases, and under local anaesthesia in 80% and general
      anaesthesia in 20%. There was no anaesthetist present in 54% of cases. Few pre-
      or peroperative arteriograms were performed. The 30-day mortality was 45%, with
      an amputation rate of 15% and an overall postoperative complication rate of 62%
      with little improvement in these figures over the last 10 years. Factors
      increasing mortality were: delay before diagnosis, grade of surgeon performing
      the operation, and inadequate inflow or outflow at operation. Factors found to
      affect limb salvage rate adversely were a history of intermittent claudication,
      although such a history was not recorded in many cases, and lack of immediate
      preoperative heparinization. Although embolectomy is considered a 'registrar
      operation', reviewing our results it can be seen that it is an uncommon
      operation, in our series eight or nine being performed annually. Sometimes
      inappropriate surgery is performed upon patients in whom severe systemic illness
      may contraindicate any form of surgical intervention.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7520078
TI  - Ultrasound assessment of the efficacy of wound drains.
AB  - We report the use of ultrasound in the assessment of the efficacy of wound drains
      in preventing wound haematoma. 171 patients with proximal femoral fractures who
      underwent AO dynamic hip screw or hemiarthroplasty were randomized as to whether
      or not they should receive wound drainage. Patients then underwent ultrasound
      examination on the 5th postoperative day to localize and quantify any wound
      haematomas. Results show that drains are effective in preventing wound
      collections, but only while in situ; following the removal of drains the size of
      resulting wound collections is the same whether the wound has been drained or not
      (Student's t-test; t = 0.19, NS). This study questions current theories on the
      mechanisms by which wound drainage is thought to influence wound healing.

PMID- 7520079
TI  - Synthesis of a series of 4-(arylethynyl)-6-chloro-4-cyclopropyl-3,4
      dihydroquinazolin-2(1H)-ones as novel non-nucleoside HIV-1 reverse transcriptase
      inhibitors.
AB  - As part of an ongoing effort to prepare novel non-nucleoside inhibitors of human
      immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT), a series of 4
      (arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin -2(1H)-ones 4aa-l has
      been prepared. Target compounds 4a-e were synthesized via addition of various 1
      lithio-2-(aryl)alkyne nucleophiles to a 1-protected-4-cyclopropylquinazolin-2(1H)
      one (7), followed by deprotection. The 3-methyl compound 4aa was prepared in an
      analogous manner, with the 3-alkylation performed prior to deprotection.
      Alternatively, the target compounds 4f-l were prepared by addition of 1-lithio-2
      (trimethylsilyl)acetylene to 7, followed by deprotection and subsequent palladium
      catalyzed coupling with various aryl halides. By incorporating an aryl group onto
      the end of the 4-acetylene functionality, the requirement for a metabolically
      labile 3-methyl group on the dihydroquinazolinone nucleus has been eliminated. A
      number of the target compounds were shown to be potent inhibitors of HIV-1 RT.
      Compound 4a, which had exhibited the most favorable overall biological profile,
      was resolved via a four-step procedure to provide the enantiomers 13a and 13b.
      Compound 13a having the (-)-4(S) configuration was shown to be the active
      enantiomer and was selected as a candidate for further investigation.

PMID- 7520080
TI  - Synthesis of naphthalenesulfonic acid small molecules as selective inhibitors of
      the DNA polymerase and ribonuclease H activities of HIV-1 reverse transcriptase.
AB  - Over 25 selected naphthalenesulfonic acid derivatives were evaluated for their
      inhibitory effect on two different functional domains of the HIV-1 reverse
      transcriptase (RT), namely the ribonuclease H and DNA polymerase activities. Most
      of the analogues were found to be either specific toward the DNA polymerase
      activity or showed nonselective inhibition of both catalytic functions. The most
      active compounds are either symmetrical derivatives or nonsymmetrical derivatives
      containing a lipophilic appendage consisting of a palmitoyl or cholesteryl
      moiety. The six most active compounds in the preliminary screen, derivatives 6,
      16, 17, 23, 26, and 27, were subjected to experiments to determine their 50%
      inhibitory concentration (IC50) values in the assays that measure RNA-dependent
      DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP), and ribonuclease H
      (RNase H) functions of HIV-1 RT. The most potent derivative was a nonsymmetric
      cholesterol-linked 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid analogue,
      compound 23, which demonstrated an IC50 value of 0.06 microM for inhibiting RDDP
      activity. Inhibition of DDDP and RNase H activity for this compound was
      demonstrated at concentrations that were over 100-fold of that for inhibiting
      RDDP activity. However, the potency of this active compound does not correlate in
      the whole virus assay, probably due to a lack of cellular entry. The cholesterol
      derivative, 23, also possesses HIV-1 protease inhibitory activity and belongs to
      a unique class of multifunctional HIV-1 inhibitors.

PMID- 7520081
TI  - HIV-1 reverse transcriptase inhibitor design using artificial neural networks.
AB  - Artificial neural networks were used to analyze and predict the human
      immunodeficiency virus type 1 reverse transcriptase inhibitors. The training and
      control sets included 44 molecules (most of them are well-known substances such
      as AZT, dde, etc.). The activities of the molecules were taken from literature.
      Topological indices were calculated and used as molecular parameters. The four
      most informative parameters were chosen and applied to predict activities of both
      new and control molecules. We used a network pruning algorithm and network
      ensembles to obtain the final classifier. Increasing of neural network
      generalization of the new data was observed, when using the aforementioned
      methods. The prognosis of new molecules revealed one molecule as possibly very
      active. It was confirmed by further biological tests.

PMID- 7520082
TI  - Thermodynamics of folding a pseudoknotted mRNA fragment.
AB  - A sequence in the leader and first gene of the Escherichia coli alpha mRNA folds
      into a complex pseudoknot structure that is required for binding of a
      translational repressor. The thermal denaturation of a 112 nt RNA containing this
      structure has been followed by calorimetry and UV hyperchromicity. To determine
      the partially folded intermediates in unfolding, the denaturation of 13 mutants
      and of several fragments with successive deletions of helices were investigated
      as well. An unfolding pathway with seven states is proposed as the simplest
      mechanism that accounts for the data, and has several implications. (1) The
      lowest temperature transition appears only in the presence of moderate
      concentrations of Mg2+ or high concentrations of K+ (delta H approximately 45
      kcal/mol), and is the unfolding of tertiary structures, rather than secondary
      structure. Under some conditions it is destabilized by increasing salt
      concentration. (2) Two of the intermediates unfolding at higher temperature must
      have non-canonical or tertiary interactions in addition to the known secondary
      structure. (3) Two alternative structures compete for formation of the complete
      pseudoknot, and form as the pseudoknot unfolds. Thus structures not present in
      the completely folded pseudoknot affect the overall thermodynamics, and probably
      the kinetics, of unfolding. (4) Approximately 16 kcal/mol of free energy is
      required to completely expose the coding region to ribosomes at 37 degrees C,
      though approximately 6.5 kcal/mol is regained by refolding of upstream regions
      after the pseudoknot is unfolded. The substantial energy needed to unfold the
      pseudoknot may affect the rate of translation from this ribosome binding site. A
      simple model of RNA folding in which an optimum secondary structure forms first,
      followed by tertiary interactions that further stabilize the secondary structure,
      does not hold in this RNA.

PMID- 7520083
TI  - Comparative structure and genomic organization of the discontinuous mitochondrial
      ribosomal RNA genes of Chlamydomonas eugametos and Chlamydomonas reinhardtii.
AB  - We report that the mitochondrial ribosomal RNAs (rRNAs) of Chlamydomonas
      eugametos are discontinuously encoded in separate gene pieces that are scrambled
      in order and interspersed with protein coding genes. Individual transcripts of
      these mitochondrial rRNA gene pieces have the potential to form standard rRNA
      secondary structures through intermolecular base-pairing and they all have
      termini that are confined to previously defined variable rRNA domains. The C.
      eugametos and the previously described Chlamydomonas reinhardtii mitochondrial
      DNAs, therefore, share the unusual feature of highly fragmented and extensively
      rearranged rRNA coding regions, which contrasts with the conventional
      mitochondrial rRNA gene structure of land plants and other green algae. Although
      many of the sites of mitochondrial rRNA discontinuity are in corresponding
      variable regions in the two Chlamydomonas species, several variable rRNA regions
      are interrupted in one species but not the other and the 5' to 3' order of the C.
      eugametos and C. reinhardtii gene pieces is very different. Based on these
      results, we conclude that the last common ancestor of C. eugametos and C.
      reinhardtii had discontinuous mitochondrial rRNA genes and that processes
      responsible for the further division and scrambling of these coding regions have
      continued since the divergence of C. eugametos and C. reinhardtii. The presence
      of four group I introns within the C. eugametos mitochondrial rRNA gene pieces
      leads us to favour recombination rather than reverse-transcription as the
      mechanism giving rise to the scrambled arrangement of rRNA genes in Chlamydomonas
      mitochondria.

PMID- 7520085
TI  - Simultaneous refinement of the structure of BPTI against NMR data measured in
      solution and X-ray diffraction data measured in single crystals.
AB  - The structure of the bovine pancreatic trypsin inhibitor (BPTI) has been
      determined to high resolution by both NMR spectroscopy in solution and X-ray
      diffraction in crystals. The root-mean-square difference calculated between the
      two structures for the polypeptide backbone is 0.9 A. Several amino acid side
      chains, of which all but one are charged or polar, have different conformations.
      We find that by refining one structure simultaneously against both the NMR and
      crystallographic data sets, it can accommodate both. Different starting
      configurations were used, including the X-ray structure 5pti, an NMR conformer,
      and the X-ray structure in the full unit cell with extra solvent placed in the
      bulk solvent region. The X-ray structures quickly converged to accommodate the
      NMR data in addition to the crystallographic data. Starting from an NMR
      conformer, however, the convergence to accommodate the more abundant X-ray data
      in addition to the NMR data is much slower.

PMID- 7520084
TI  - Crystal structure of a peptide complex of anti-influenza peptide antibody Fab
      26/9. Comparison of two different antibodies bound to the same peptide antigen.
AB  - The three-dimensional structure of the complex of a second anti-peptide antibody
      (Fab 26/9) that recognizes the same six-residue epitope of an immunogenic peptide
      from influenza virus hemagglutinin (HA1; 75-110) as Fab 17/9 with the peptide has
      been determined at 2.8 A resolution. The amino acid sequence of the variable
      region of the 26/9 antibody differs in 24 positions from that of 17/9, the first
      antibody in this series for which several ligand-bound and free structures have
      been determined and refined. Comparison of the 26/9-peptide with the 17/9-peptide
      complex structures shows that the two Fabs are very similar (r.m.s.d. 0.5 to 0.8
      A) and that the peptide antigen (101-107) has virtually the same conformation
      (r.m.s.d. 0.3 to 0.8 A) when bound to both antibodies. A sequence difference in
      the 26/9 binding pocket (L94; His in 26/9, Asn in 17/9) results in an interaction
      with a bound water molecule that is not seen in the 17/9 structures. Epitope
      mapping shows that the relative specificity of 26/9 and 17/9 antibodies for
      individual positions of the peptide antigen are slightly different. Amino acid
      substitutions in the peptide, particularly at position SerP107, are tolerated to
      different extents by 17/9 and 26/9. Structural and sequence analysis suggests
      that amino acid differences near the peptide-binding site are responsible for
      altering slightly the specificity of 26/9 for three peptide residues and
      illustrates how amino acid substitutions can modify antibody-antigen interactions
      and thereby modulate antibody specificity.

PMID- 7520087
TI  - Changes of beta-amyloid precursor protein splice patterns in brain cell aggregate
      cultures.
AB  - The splice pattern of beta-amyloid precursor protein (beta-APP) has been studied
      in a variety of neuronal and glial cells and in brain cell aggregate cultures by
      the polymerase chain reaction (PCR). The brain-typical pattern, in which beta
      APP695 is the dominant form, has been found only in aggregate cultures but not in
      any of the other cell types including neuronal cell lines. Selective elimination
      of glial cells from aggregates resulted in increased quantities of beta-APP695,
      whereas removal of neurons led to a reduction of beta-APP695 and to an elevation
      of beta-APP751 and beta-APP770. This shift of splice pattern was not observed in
      cocultures of the neuronal cell line PC 12 with primary astrocytes combined in a
      variety of cellular ratios. Blood serum, which is an essential component of these
      cultures, tested on aggregates, did not reduce the amount of beta-APP695 or have
      any marked effects on splice patterns generally. From these results it is
      concluded that investigations on brain-typical splicing of beta-APP require
      primary neurons. Neuronal cell lines may be no suitable model systems. Splicing
      events favoring production of beta-APP695 may mark an important, very early step
      of amyloid formation in the brain.

PMID- 7520086
TI  - Extracellular ATP-induced currents in astrocytes: involvement of a cation
      channel.
AB  - Whole-cell currents were measured with the perforated patch clamp technique in
      cultured rat astrocytes to analyze the underlying ionic mechanism for a P2
      purinoceptor-mediated depolarization. ATP (100 microM) induced an inward current
      with a mean amplitude of 130 pA and an EC50 of 17 microM. The response
      desensitized during a 1 min application. Replacement of extracellular Na+ with
      NMDG or K+ abolished the ATP-evoked inward current. Replacement of Na+ with
      choline, however, resulted in an ATP-evoked response of one-third the amplitude
      in normal solution. This is indicative of a cation rather than Na+ channel.
      However, due to difficulties in voltage-clamping these gap junction-coupled cells
      at voltages different from the membrane resting potential, the current reversal
      potential could not be determined. Measurements with K(+)-sensitive
      microelectrodes showed that 100 microM ATP lowered the intracellular K+
      concentration. Replacement of extracellular Ca2+ or Cl- did not alter the ATP
      induced inward currents. Fura-2 imaging experiments revealed a transient rise of
      the intracellular Ca2+ concentration during ATP application. Removal of
      extracellular Ca2+ did not influence the peak response; it did, however, shorten
      the time course. These results and previous observations that the permeability
      changes are caused by a P2x receptor are indicative of an ATP-sensitive cation
      conductance. In addition, cytoplasmic Ca2+ is increased by mobilization from
      intracellular stores, and by additional influx across the cell membrane.
      Extracellular ATP released by neurons could evoke K+ release from astrocytes as
      well as be a mediator for cation changes that signal cell activation processes
      when released by damaged cells.

PMID- 7520088
TI  - Depolarizing agents and tumor necrosis factor-alpha modulate protein
      phosphorylation in oligodendrocytes.
AB  - Membrane depolarization and changes in ionic fluxes have been implicated in the
      signaling mechanisms between neurons and glial cells. We report here that K(+)
      induced depolarization of cultured ovine oligodendrocytes (OLGs) decreases the
      phosphorylation of myelin basic protein (MBP) and 2'3'-cyclic nucleotide
      phosphohydrolase (CNPase). Membrane depolarization and decrease in
      phosphorylation of MBP and CNPase can also be elicited by inhibition of the
      inward rectifier with Ba2+ but not by inhibition of outward K+ channels with 4
      aminopyridine or tetraethylammonium. These findings demonstrate that modulation
      of K+ currents can influence phosphorylation states of OLG proteins. Tumor
      necrosis factor-alpha (TNF-alpha), an immune peptide implicated in autoimmune
      demyelinating diseases, also inhibits the phosphorylation of these proteins. In
      contrast to elevated [K+]o, TNF-alpha does not decrease the stimulatory effect of
      protein kinase C activators or phosphatase inhibitors on MBP and CNPase
      phosphorylation, suggesting that depolarizing agents and TNF-alpha act via
      distinct mechanisms. We postulate that the presence of elevated extracellular K+
      and/or cytokines under certain pathological conditions can perturb OLG function
      by altering the phosphorylation states of their proteins and perhaps affect
      myelin maintenance, contributing to demyelination.

PMID- 7520090
TI  - Localization of neutralizing epitopes and the receptor-binding site within the
      amino-terminal 330 amino acids of the murine coronavirus spike protein.
AB  - To localize the epitopes recognized by monoclonal antibodies (MAbs) specific for
      the S1 subunit of the murine coronavirus JHMV spike protein, we have expressed S1
      proteins with different deletions from the C terminus of S1. S1utt is composed of
      the entire 769-amino-acid (aa) S1 protein; S1NM, S1N, S1n(330), and S1n(220) are
      deletion mutants with 594, 453, 330, and 220 aa from the N terminus of the S1
      protein. The expressed S1 deletion mutant proteins were examined for reactivities
      to a panel of MAbs. All MAbs classified in groups A and B, those reactive to most
      mouse hepatitis virus (MHV) strains and those specific for isolate JHMV,
      respectively, recognized S1N(330) and the larger S1 deletion mutants but failed
      to react with S1N(220). MAbs in group C, specific for the larger S protein of
      JHMV, reacted only with the S1utt protein without any deletion. These results
      indicated that the domain composed of the N-terminal 330 aa comprised the cluster
      of conformational epitopes recognized by MAbs in groups A and B. It was also
      shown that the epitopes of MAbs in group C were not restricted to the region
      missing in the smaller S protein. These results together with the fact that all
      MAbs in group B retained high neutralizing activity suggested the possibility
      that the N-terminal 330 aa are responsible for binding to the MHV-specific
      receptors. In investigate this possibility, we expressed the receptor protein and
      examined the binding of each S1 deletion mutant to the receptor. It was
      demonstrated that the S1N(330) protein as well as other S1 deletion mutants
      larger than S1N(330) bound to the receptor. These results indicated that a domain
      composed of 330 aa at the N terminus of the S1 protein is responsible for binding
      to the MHV-specific receptor.

PMID- 7520091
TI  - A protease-sensitive hinge linking the two domains of the hepatitis B virus core
      protein is exposed on the viral capsid surface.
AB  - Core particles of hepatitis B virus are assembled from dimers of a single 185
      residue (subtype adw) viral capsid or core protein (p21.5) which possesses two
      distinct domains: residues 1 to 144 form a minimal capsid assembly domain, and
      the arginine-rich, carboxyl-terminal residues 150 to 185 form a protamine-like
      domain that mediates nucleic acid binding. Little is known about the topography
      of the p21.5 polypeptide within either the p21.5 capsids or dimers. Here, using
      site-specific proteases and monoclonal antibodies, we have defined the
      accessibility of p21.5 residues in dimers and capsids assembled from wild-type
      and mutant hepatitis B virus core proteins in Xenopus oocytes and in vitro. The
      data reveal the protamine region to be accessible to external reagents in p21.5
      dimers but largely cryptic in wild-type capsids. Strikingly, in capsids the only
      protease target region was a 9-residue peptide covering p21.5 residues Glu-145 to
      Asp-153, which falls largely between the two core protein domains. By analogy
      with protease-sensitive interdomain regions in other proteins, we propose that
      this peptide constitutes a hinge between the assembly and nucleic acid binding
      domains of p21.5. We further found that deletion or replacement of the terminal
      Cys-185 residue greatly increased surface exposure of the protamine tails in
      capsids, suggesting that a known disulfide linkage involving this residue tethers
      the protamine region inside the core particles. We propose that disruption of
      this disulfide linkage allows the protamine region to appear transiently on the
      surface of the core particle.

PMID- 7520089
TI  - Effects of natural sequence variation on recognition by monoclonal antibodies
      neutralize simian immunodeficiency virus infectivity.
AB  - The determinants of immune recognition by five monoclonal antibodies (KK5, KK9,
      KK17, Senv7.1, and Senv101.1) that neutralize simian immunodeficiency virus
      infectivity were analyzed. These five neutralizing monoclonal antibodies were
      generated to native SIVmac251 envelope glycoprotein expressed by a vaccinia virus
      recombinant vector. All five recognize conformational or discontinuous epitopes
      and require native antigen for optimal recognition. These monoclonal antibodies
      also recognize SIVmac239 gp120, but they do not recognize gp120 of two natural
      variants of SIVmac239, 1-12 and 8-22, which evolved during the course of
      persistent infection in vivo (D.P.W. Burns and R.C. Desrosiers, J. Virol. 65:1843
      1854, 1991). Recombinant viruses which were constructed by exchanging variable
      regions between SIVmac239 and variant 1-12 were used to define domains important
      for recognition. Radioimmunoprecipitation analysis demonstrated that sequence
      changes in variable regions 4 and 5 (V4/V5) were primarily responsible for the
      loss of recognition of the 1-12 variant. Site-specific mutants were used to
      define precise changes that eliminate recognition by these neutralizing
      antibodies. Changing N-409 to D, deletion of KPKE, and deletion of KEQH in V4
      each resulted in loss of recognition by all five monoclonal antibodies. SIVs with
      these natural sequence changes are still replication competent and viable.
      Changing A-417 to T or A/N-417/418 to TK in V4 or Q-477 to K in V5 did not alter
      recognition detectably. These results define specific, naturally occurring
      sequence changes in V4 of SIVmac that result in loss of recognition by one class
      of SIVmac neutralizing antibodies.

PMID- 7520092
TI  - Site-specific RNA binding by a hepatitis B virus reverse transcriptase initiates
      two distinct reactions: RNA packaging and DNA synthesis.
AB  - Hepatitis B viruses encode a polymerase (P) protein with key roles in both
      reverse transcription and genomic RNA encapsidation. Genetic analysis of cis
      acting signals required for viral replication implicates an RNA stem-loop
      structure in both RNA packaging and the initiation of reverse transcription, a
      process in which P protein also serves as the primer. We now show that duck
      hepatitis B virus (DHBV) polymerase binds specifically and with high affinity to
      this RNA stem-loop structure. Mutational analysis indicates that all mutations in
      the RNA target that inhibit the P protein-RNA interaction inhibit both in vivo
      RNA packaging and in vitro DNA priming to comparable extents. However, certain
      mutations in the loop region of the RNA have minimal impact on P protein-RNA
      binding but are nonetheless severely defective for packaging and DNA synthesis.
      Thus, P protein-RNA complex formation is necessary but not sufficient to initiate
      these activities. In addition, examination of RNA binding by truncated P proteins
      indicates that the C terminus of the polymerase, although required for RNA
      encapsidation in vivo, is dispensable for RNA binding and DNA priming.

PMID- 7520093
TI  - Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1: a B
      cell-specific response that is delayed relative to NF-kappa B activation and to
      induction of cell surface markers.
AB  - An ability of the Epstein-Barr virus latent membrane protein LMP1 to enhance the
      survival of infected B cells through upregulation of the bcl-2 oncogene was first
      suggested by experiments involving gene transfection and the selection of stable
      LMP1+ clones (S. Henderson, M. Rowe, C. Gregory, F. Wang, E. Kieff, and A.
      Rickinson, Cell 65:1107-1115, 1991). However, it was not possible to ascertain
      whether Bcl-2 upregulation was a specific consequence of LMP1 expression or an
      artifact of the selection procedure whereby rare Bcl-2+ cells already present in
      the starting population might best be able to tolerate the potentially toxic
      effects of LMP1. We therefore reexamined this issue by using two different
      experimental approaches that allowed LMP1-induced effects to be monitored
      immediately following expression of the viral protein and in the absence of
      selective pressures; activation of the NF-kappa B transcription factor and
      upregulation of the cell adhesion molecule ICAM-1 were used as early indices of
      LMP1 function. In the first approach, stable clones of two B-cell lines carrying
      an LMP1 gene under the control of an inducible metallothionein promoter were
      induced to express LMP1 in all cells. Activation of NK-kappa B and upregulation
      of ICAM-1 occurred within 24 h and were followed at 48 to 72 h by upregulation of
      Bcl-2. In the second approach, we tested the generality of this phenomenon by
      transiently expressing LMP1 from a strong constitutively active promoter in a
      range of different cell types. All six B-cell lines tested showed NF-kappa B
      activation in response to LMP1 expression, and this was followed in five of six
      lines by expression of ICAM-1 and Bcl-2. In the same experiments, all three non-B
      cell lines showed NF-kappa B activation and ICAM-1 upregulation but never any
      effect upon Bcl-2. We therefore conclude that Bcl-2 upregulation is part of the
      panoply of cellular changes induced by LMP1 but that the effect is cell type
      specific. Our data also suggest that whilst NF-kappa B may be an essential
      component of LMP1 signal transduction, other cell-specific factors may be
      required to effect some functions of the viral protein.

PMID- 7520094
TI  - Contributions of DNA polymerase subdomains to the RNase H activity of human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - Previous studies showed that an isolated human immunodeficiency virus type 1 (HIV
      1) RNase H domain expressed as a fusion protein is highly active in Mn2+, but
      activity was dependent on a hexahistidine tag located at either the carboxyl or
      amino terminus of the fusion protein (J. Smith and M. Roth, J. Virol. 67:4037
      4049, 1993). It was postulated that a histidine tag can somehow provide a
      function normally associated with the DNA polymerase domain of HIV-1 reverse
      transcriptase. To determine the contributions of the DNA polymerase subdomains of
      HIV-1 reverse transcriptase to its RNase H activity, we have characterized the
      activity of isolated RNase H domains which include either portions of the
      connection, the entire connection, or both the thumb and connection as N-terminal
      extensions. Including increasing lengths of these domains at the N terminus of
      the RNase H resulted in a progressive increase in Mn(2+)-dependent RNase H
      activity that was independent of a histidine tag. Activity of the isolated RNase
      H domains was also stimulated by the addition of independently purified
      polymerase subdomains. Further, this stimulation was shown to be a result of
      direct physical interactions between the thumb, connection, and RNase H domains.
      The connection and thumb subdomains were shown to contribute to substrate
      binding. The fingers and palm subdomains were found to be essential for Mg(2+)
      dependent RNase H activity.

PMID- 7520096
TI  - Analysis of a rape case by direct sequencing of the human immunodeficiency virus
      type 1 pol and gag genes.
AB  - Transmission of human immunodeficiency virus type 1 (HIV-1) from a male accused
      of rape and deliberate transmission of HIV-1 was investigated by sequencing of
      the HIV-1 pol and gag genes from virus obtained from the male and from the female
      victim. Parts of the reverse transcriptase and p17gag genes were amplified and
      directly sequenced from uncultured peripheral blood mononuclear cells. The
      sequences were compared with sequences from 21 unrelated HIV-1-infected controls
      from the same geographic area (Stockholm, Sweden). Bootstrap analysis of
      phylogenetic trees demonstrated that the sequences from the female were
      significantly more closely related to the sequences from the male than to
      sequences from the controls. Furthermore, we found that the male and female
      shared two distinct genetic variants of HIV-1. In p17gag the major variant had an
      unusual, out-of-frame deletion of 3 nucleotides which the minor variant lacked.
      These results indicated that the male had transmitted more than one infectious
      unit to the female. From this study we concluded that it was highly likely that
      the HIV-1 strains carried by the male and female were closely epidemiologically
      linked.

PMID- 7520095
TI  - Immunization with a soluble CD4-gp120 complex preferentially induces neutralizing
      anti-human immunodeficiency virus type 1 antibodies directed to conformation
      dependent epitopes of gp120.
AB  - Preservation of the conformation of recombinant gp120 in an adjuvant, enabling it
      to elicit conformation-dependent, epitope-specific, broadly neutralizing
      antibodies, may be critical for the development of any gp120-based human
      immunodeficiency virus type 1 (HIV-1) vaccine. It was hypothesized that
      recombinant gp120 complexed with recombinant CD4 could stabilize the conformation
      dependent neutralizing epitopes and effectively deliver them to the immune
      system. Therefore, a soluble CD4-gp120 complex in Syntex adjuvant formulation was
      tested with mice for its ability to induce neutralizing anti-gp120 antibody
      responses. Seventeen monoclonal antibodies (MAbs) were generated and
      characterized. Immunochemical studies, neutralization assays, and mapping studies
      with gp120 mutants indicated that the 17 MAbs fell into three groups. Four of
      them were directed to what is probably a conformational epitope involving the C1
      domain and did not possess virus-neutralizing activities. Another four MAbs bound
      to V3 peptide 302-321 and exhibited cross-reactive gp120 binding and relatively
      weak virus-neutralizing activities. These MAbs were very sensitive to amino acid
      substitutions, not only in the V3 regions but also in the base of the V1/V2 loop,
      implying a conformational constraint on the epitope. The last group of nine MAbs
      recognized conformation-dependent epitopes near the CD4 binding site of gp120 and
      inhibited the gp120-soluble CD4 interaction. Four of these nine MAbs showed
      broadly neutralizing activities against multiple laboratory-adapted strains of
      HIV-1, three of them neutralized only HIVIIIB, and the two lower-affinity MAbs
      did not neutralize any strain tested. Collectively, the results from this study
      indicate that immunization with the CD4-gp120 complex can elicit antibodies to
      conformationally sensitive gp120 epitopes, with some of the antibodies having
      broadly neutralizing activities. We suggest that immunization with CD4-gp120
      complexes may be worth evaluating further for the development of an AIDS vaccine.

PMID- 7520097
TI  - Vitronectin receptor antibodies inhibit infection of HeLa and A549 cells by
      adenovirus type 12 but not by adenovirus type 2.
AB  - The penton base gene from adenovirus type 12 (Ad12) was sequenced and encodes a
      497-residue polypeptide, 74 residues shorter than the penton base from Ad2. The
      Ad2 and Ad12 proteins are highly conserved at the amino- and carboxy-terminal
      ends but diverge radically in the central region, where 63 residues are missing
      from the Ad12 sequence. Conserved within this variable region is the sequence Arg
      Gly-Asp (RGD), which, in the Ad2 penton base, binds to integrins in the target
      cell membrane, enhancing the rate or the efficiency of infection. The Ad12 penton
      base was expressed in Escherichia coli, and the purified refolded protein
      assembled in vitro with Ad2 fibers. In contrast to the Ad2 penton base, the Ad12
      protein failed to cause the rounding of adherent cells or to promote attachment
      of HeLa S3 suspension cells; however, A549 cells did attach to surfaces coated
      with either protein and pretreatment of the cells with an integrin alpha v beta 5
      monoclonal antibody reduced attachment to background levels. Treatment of HeLa
      and A549 cells with integrin alpha v beta 3 or alpha v beta 5 monoclonal
      antibodies or with an RGD-containing fragment of the Ad2 penton base protein
      inhibited infection by Ad12 but had no effect on and in some cases enhanced
      infection by Ad2. Purified Ad2 fiber protein reduced the binding of radiolabeled
      Ad2 and Ad12 virions to HeLa and A549 cells nearly to background levels, but the
      concentrations of fiber that strongly inhibited infection by Ad2 only weakly
      inhibited Ad12 infection. These data suggest that alpha v-containing integrins
      alone may be sufficient to support infection by Ad12 and that this pathway is not
      efficiently used by Ad2.

PMID- 7520099
TI  - The Utah children's GunWise Program: another emergency nurse makes a difference.

PMID- 7520100
TI  - p210 bcr-abl confers overexpression of inosine monophosphate dehydrogenase: an
      intrinsic pathway to drug resistance mediated by oncogene.
AB  - The p210 bcr-abl fusion protein tyrosine kinase oncogene has been implicated in
      the pathogenesis of chronic granulocytic leukemia (CGL). Specific intracellular
      functions performed by p210 bcr-abl have recently been delineated. We considered
      the possibility that p210 bcr-abl may also regulate the abundance of inosine 5'
      monophosphate dehydrogenase (IMPDH) which is a rate-limiting enzyme for de novo
      guanylate synthesis. We performed studies of the inhibition of IMPDH by
      tiazofurin, which acts as a competitive inhibitor through its active species that
      mimics nicotinamide adenine dinucleotide (NAD), i.e. thiazole-4-carboxamide
      adenine dinucleotide (TAD). The mean inhibitory concentration (IC50) of
      tiazofurin for cellular proliferation inhibition was 2.3-2.8-fold greater in
      cells expressing p210 bcr-abl than in their corresponding parent cells
      proliferating under the influence of growth factors or in growth factor
      independent derivative cells not expressing detectable p210 bcr-abl. IMPDH
      activity was 1.5-2.3-fold greater within cells expressing p210 bcr-abl than in
      their parent cells. This increase in enzyme activity was a result of 2-fold
      increased IMPDH protein as determined by immunoblotting. In addition, an increase
      in the Km value for NAD utilization by IMPDH was observed in p210 bcr-abl
      transformed cells, but this increase was within the range of resident NAD
      concentrations observed in the cells. Increased IMPDH protein in p210 bcr-abl
      transformed cells was traced to an increased level of IMP dehydrogenase II
      messenger RNA. Thus, regulation of IMPDH gene expression is mediated at least in
      part by the bcr-abl gene product and may therefore be indicative of a specific
      mechanism of intrinsic resistance to tiazofurin.

PMID- 7520101
TI  - Potentiated maturation with a high proliferating activity of acute promyelocytic
      leukemia induced in vitro by granulocyte or granulocyte/macrophage colony
      stimulating factors in combination with all-trans retinoic acid.
AB  - All-trans retinoic acid (ATRA) induces differentiation of acute promyelocytic
      leukemia (APL), but the effect of cytokines regulating myeloid differentiation on
      ATRA-induced APL cells is poorly understood. In this study, maturation and
      proliferation of fresh APL cells were examined when induced in vitro by
      granulocyte or granulocyte/macrophage colony-stimulating factors (G-CSF or GM
      CSF) in combination with ATRA. APL cells showed a low proliferating activity when
      induced by ATRA alone. In contrast, cells induced by G-CSF or GM-CSF alone showed
      increased DNA syntheses, the levels of which were not significantly affected by
      the combination of ATRA with CSFs. Interestingly, G-CSF or GM-CSF potentiated the
      capability of ATRA-induced cells to reduce nitroblue tetrazolium (NBT), while G
      CSF or GM-CSF alone induced no NBT reduction. Furthermore, in several patients
      examined, APL cells induced by ATRA with G-CSF showed an increased activity of
      chemotaxis and CD11a expression. These findings suggest that G-CSF or GM-CSF can
      potentiate differentiation of ATRA-induced APL cells while stimulating their
      proliferating activity as well, and that G-CSF, rather than GM-CSF, may be a
      useful adjunct to promote ATRA-induced differentiation of APL.

PMID- 7520098
TI  - Identification of an H-2 Kb-presented Moloney murine leukemia virus cytotoxic T
      lymphocyte epitope that displays enhanced recognition in H-2 Db mutant bm13 mice.
AB  - Upon infection with the Moloney murine sarcoma virus-murine leukemia virus (MuLV)
      complex, H-2b C57BL/6 (B6) mice respond with a class I Db-restricted cytotoxic T
      lymphocyte (CTL) response, which protects against virus-induced tumorigenesis. In
      the B6-derived Db mutant B6.CH-2bm13 (bm13) strain, part of the class I Db
      antigen-presenting groove is shaped by a class I Kb-encoded sequence. Like B6
      mice, bm13 mice reject Moloney virus-induced tumors, but the protective CTL
      response is Kb restricted. In this study we show enhanced levels of Moloney MuLV
      specific CTLp with a restriction for Kb in bm13 mice. Through the use of CTL
      clones from Moloney virus-immunized bm13 mice, the class I Kb-presented CTL
      epitope was identified. The epitope is located in the Moloney virus gp70 envelope
      protein region (Moloney envelope, amino acids 189 to 196 [Mol env (189-196)]),
      SSWDFITV and has the Kb allele-specific binding motif. The Dbm13 molecule does
      not present the env(189 to 196) epitope to Kb-restricted bm13 CTL. In B6 mice,
      Mol env(189-196)-specific CTL could be induced by peptide vaccination. B6 mice
      thus have CTL precursors specific for this epitope but at considerably lower
      levels than do bm13 mice. We hypothesize that additional positive selection of Kb
      restricted CTL on the Dbm13 molecule in bm13 mice explains this difference in
      precursor frequencies. We examined related strains of MuLV for the presence of
      Mol env(189-196) sequence equivalents. Rauscher, Friend, and AKV MuLV-encoded Mol
      env(189-196) epitope equivalents were properly recognized in cytotoxicity assays,
      both as synthetic and as endogenously expressed (Rauscher MuLV) peptides. In
      contrast, the mink cell focus-forming virus MuLV-encoded epitope equivalent,
      lacking a Kb anchor residue, was not presented for CTL recognition and hence can
      be excluded as an important CTL epitope for mink cell focus-forming viruses.

PMID- 7520102
TI  - Application of a new protocol for nested PCR to the detection of minimal residual
      bcr/abl transcripts.
AB  - Nested PCR (NPCR), a two-step procedure in which the products of a first PCR
      using 'outer' primers are reamplified using 'inner primers', has been
      successfully used to test for the chronic myeloid leukemia (CML)-specific bcr-abl
      transcripts. A major drawback of the conventional nesting strategy is linked to
      the opening of the reaction tube between the two successive PCR reactions, giving
      a risk of contaminating the second mix with amplicons. In this paper, the
      application of a new protocol for NPCR without reopening the reaction tube
      between the two steps of the procedure is described for the research of residual
      leukemic cells in the peripheral blood of 14 CML patients treated by bone marrow
      transplantation (BMT) or interferon (IFN). This assay which is both highly
      specific and sensitive, offers several advantages over the use of conventional
      NPCR: it is more sensitive, faster and decreases the risk of false-positive
      results. In addition, chemiluminescent detection of amplified DNA after transfer
      onto a nylon membrane, although comparable with radioactive hybridization in
      terms of sensitivity and speed, is more advantageous in safety and convenience.
      In conclusion, this assay could be adapted to a number of clinical diagnostic
      uses.

PMID- 7520103
TI  - Effective treatment of mycoplasma contamination in cell lines with enrofloxacin
      (Baytril).
AB  - Continuous cell lines are frequently contaminated with microorganisms,
      mycoplasmas being the most prominent and cumbersome. In our experience, of the
      300 cell lines examined more than one third was infected with mycoplasmas.
      Mycoplasma contamination can affect virtually every parameter and functional
      activity of a cultured cell. An alternative to the recommended disposal of
      infected cultures is an attempt to eliminate the contaminants. Adding antibiotics
      with strong activity against mycoplasmas to the culture medium is a simple,
      inexpensive and efficient decontamination method. Here, we studied the
      effectiveness of the new antibiotic enrofloxacin (Baytril) developed specifically
      for use against mycoplasmas. Baytril is a new synthetic agent from the group of
      quinolone derivatives that are DNA gyrase inhibitors. Thirty-two chronically
      infected cell lines (27 human leukemia-lymphoma cell lines) were treated with
      Baytril in a prospective study in direct comparison with three other well
      established anti-mycoplasma regimens, the antibiotics BM-Cyclin, Ciprobay and MRA
      (Mycoplasma Removal Agent). Mycoplasmas were detected by DNA staining, agar
      colony growth, DNA-RNA hybridization, polymerase chain reaction, and monoclonal
      antibody staining. Treatment with Baytril eliminated the contaminants in 30/32
      cultures (94%). The cure rates for Ciprobay, BM-Cyclin and MRA were 91%, 81%, and
      75%, respectively. The IC50 values of Baytril for cell lines varied over a wide
      range depending on the type of hematopoietic cell lineage with T- and B-cell
      lines being more sensitive targets. Baytril-treated cell lines remained
      mycoplasma-negative over a 12-week antibiotic-free culture period. Low levels of
      mycoplasma infection were shown not to persist by repeat testing after growth
      without antibiotics. A retrospective analysis of anti-mycoplasma treatments with
      BM-Cyclin, Ciprobay, MRA or Baytril showed that 265/351 cultures (75%) were
      immediately cured of mycoplasma; however, all of the remaining, mycoplasma
      positive cultures harboring mycoplasms resistant to the first antibiotic could be
      cleaned up by a second round with a different antibiotic. Baytril is an efficient
      anti-mycoplasma antibiotic and based on its high cure rate might be the treatment
      of first choice.

PMID- 7520104
TI  - [Anti-HIV-therapy. Monotherapy with drugs delaying the course of the disease has
      limited effect].

PMID- 7520105
TI  - Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of
      liver allograft rejection. European FK506 Multicentre Liver Study Group.
AB  - Studies in the USA and Japan have shown that tacrolimus (FK506) is a potent
      immunosuppressant. To compare the efficacy and safety of tacrolimus-based and
      conventional cyclosporin-based immunosuppressive regimens we recruited 545 liver
      transplant recipients from eight European centres into a randomised open trial.
      Analysis of the data at 12 months post-transplant showed that tacrolimus was
      associated with a significant reduction in acute, refractory acute, and chronic
      rejection episodes. The rates were, for acute rejection, tacrolimus 40.5% vs
      49.8% cyclosporin (p = 0.040; absolute difference 9.3% [95% CI 0.9-17.8%]). For
      refractory acute and chronic rejections the comparisons were 0.8% vs 5.3% (p =
      0.005) and 1.5% vs 5.3% (p = 0.032). There results were seen despite
      significantly lower corticosteroid usage. The incidence of infection was also
      lower in patients receiving tacrolimus. Patient and graft survival rates were not
      significantly different (tacrolimus 82.9% and 77.5%; cyclosporin 77.5% and
      72.6%). Safety data were comparable--the most serious events being renal
      impairment, disturbances of glucose metabolism, and neurological complications-
      but these events were more common in the tacrolimus group. In this trial
      tacrolimus had advantages over cyclosporin in respect of lower rejection rates,
      even though less concurrent immunosuppression was administered.

PMID- 7520106
TI  - Relative concentrations of endotoxin-binding proteins in body fluids during
      infection.
AB  - Endotoxin initiates the systemic inflammatory response, haemodynamic changes, and
      multi-organ failure that may occur as a consequence of systemic gram-negative
      bacterial infection. The serum protein lipopolysaccharide-binding protein (LBP)
      binds to the lipid A component of bacterial endotoxin and facilitates its
      delivery to the CD14 antigen on the macrophage, where inflammatory cytokines are
      released and a cascade of host mediators is initiated. The neutrophil granular
      protein bactericidal/permeability-increasing protein (BPI) competes with LBP for
      endotoxin binding and functions as a molecular antagonist of LBP-endotoxin
      interactions. We have measured concentrations of both proteins in body fluids
      from 49 consecutive patients. In 16 of 17 samples of fluid from closed-space
      infections, BPI was present in greater concentration than LBP (median BPI/LBP
      ratio 7.6 [95% CI 2.32-22.1]). The ratio of BPI and LBP was not significantly
      different from 1.0 in abdominal fluid from 10 patients with peritonitis (ratio
      0.235 [0.18-0.47]), whereas the BPI/LBP ratio was low in 22 non-infected body
      fluids (0.01 [0.001-0.04]) and concentrations of both proteins approached those
      in normal human plasma. BPI concentrations were directly correlated with the
      quantity of neutrophils within clinical samples (rs = 0.81, p < 0.0001). Thus,
      within abscess cavities BPI is available in sufficient quantities for effective
      competition with LBP for endotoxin. BPI may attenuate the local inflammatory
      response and the systemic toxicity of endotoxin release during gram-negative
      infections.

PMID- 7520107
TI  - Disseminated intravascular coagulation after aortic aneurysm repair,
      intraoperative salvage autotransfusion, and aprotinin.

PMID- 7520108
TI  - Pulmonary toxicity of bleomycin: is G-CSF a risk factor?

PMID- 7520109
TI  - Post-transplantation survival of cystic fibrosis patients infected with
      Pseudomonas cepacia.

PMID- 7520110
TI  - Antidepressant activity and mania associated with risperidone treatment of
      schizoaffective disorder.

PMID- 7520111
TI  - DNA sequences encoding enolase are remarkably conserved from yeast to mammals.
AB  - Enolase (2-phospho-D-glycerate hydrolase, EC 4.2.1.11), particularly isoform
      neuron-specific enolase (NSE), is primarily localized in neurons and
      neuroendocrine cells and is a cancer diagnostic marker for brain tumors. Homology
      of enolase-coding DNA sequences from human, dog, cow, rat, mouse, rabbit,
      chicken, and yeast cells was investigated using hybridization techniques, percent
      sequence divergence, and amino acid analysis. Because enolase is a significant
      enzyme of the glycolytic pathway, enolase-coding DNA sequences have been found in
      all organisms tested so far. The human enzyme was found to be more like those of
      monkey and dog in structure than to those of chicken and yeast. The implications
      of the existence of the genetic conservation of enolase-coding DNA sequences in
      understanding concerted evolution as well as post-transcriptional regulation
      during differentiation are discussed. This is the first report is which sequence
      divergence in the coding region for enolase has been determined in a variety of
      organisms.

PMID- 7520112
TI  - Epitope mapping of six monoclonal antibodies recognizing the Shigella dysenteriae
      type 1 O-antigenic repeating unit expressed in Escherichia coli K-12.
AB  - Mouse and rat monoclonal antibodies were generated against lipopolysaccharides
      expressed in Escherichia coli K-12/Shigella dysenteriae type 1 hybrids and native
      Shigella dysenteriae type 1 bacteria. Six monoclonal antibodies, all IgM and
      reacting with the E. coli K-12/Shigella dysenteriae type 1 hybrids, were selected
      and characterized. The specificities were studied in inhibition experiments using
      purified native and synthetic saccharides, representing different parts of the S.
      dysenteriae type 1 tetrasaccharide repeating unit. Three patterns of
      specificities were seen: (i) MAEC-SD-1 and MAEC-SD-2 recognizing the terminal
      alpha-D-Galp-(1-->3)-beta-D-GlcpNAc disaccharide as present in an E. coli K-12
      class I hybrid strain, (ii) MAEC-SD-11; a class IV specific mAb, recognizing the
      alpha-L-Rhap-(1-->2)-alpha-D-Galp-(1-->3)-beta-D-GlcpNAc-(1-->tris accharide, and
      (iii) MAEC-SD-21, MASD-1, MASD-2; all mAbs with class V specificity, recognizing
      the alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-D-Galp-(1--> trisaccharide.
      Furthermore, the data strongly suggest that the native repeating unit for S.
      dysenteriae type 1 is the alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-D-Galp
      (1--> 3)-alpha-D-GlcpNAc tetrasaccharide.

PMID- 7520113
TI  - Lipopolysaccharide O-antigen biosynthesis in Shigella dysenteriae serotype 1:
      analysis of the plasmid-carried rfp determinant.
AB  - The O-antigen polysaccharide of the lipopolysaccharide of Shigella dysenteriae
      serotype 1 is encoded by determinants located on a 9 kb plasmid (rfp) and on the
      chromosome near the his locus (rfb). Molecular genetic and biochemical studies of
      the rfp determinant reported here show that the rfp region contains two genes,
      rfpA and rfpB, lying in an operon. rfpB was demonstrated to encode a membrane
      bound galactosyl-transferase. The low G+C content of rfp DNA suggests that it did
      not originate in Shigella.

PMID- 7520114
TI  - The concentrations of stable RNA and ribosomes in Rickettsia prowazekii.
AB  - The obligate intracellular parasite, Rickettsia prowazekii, is a slow-growing
      bacterium with a doubling time of about 10 h. In the present study, DNA and RNA
      were obtained from the rickettsiae by two independent methods, i.e. simultaneous
      isolation of DNA and RNA from the same sample by phenol:chloroform extraction and
      CsCI gradient centrifugation. In addition, ribosomal RNA was obtained by
      sedimentation of partially purified ribosomes from the rickettsiae. The results
      demonstrated that, after correction for the cell volumes, the concentrations of
      stable RNA and ribosomes in R. prowazekii, a slow-growing organism, were about 62
      fg micron-3 and 17,000 per micron3, respectively, which were very similar (66 fg
      micron-3 and 21,000 per micron3) to those in Escherichia coli with a generation
      time of 40 min. However, on a per cell basis, R. prowazekii had 5.6 fg of RNA and
      1500 ribosomes per cell, which was only about 8% of the amount of both stable RNA
      (71.2 fg) and ribosomes (24,000) per cell as was found in E. coli. These results
      indicated that R. prowazekii possesses a ribosome concentration greater than
      might have been predicted from its slow growth rate. This high concentration of
      ribosomes could be due to a large population of nonfunctioning ribosomes, a low
      efficiency of amino acid production, or a high rate of protein turnover. However,
      this study also demonstrated that the rickettsiae have very limited protein
      turnover. Knowledge of the kinetics and control mechanisms for protein synthesis
      in R. prowazekii remains to be established to determine the logic of the extra
      rickettsial ribosomes.

PMID- 7520115
TI  - Phosphorolytic error correction during transcription.
AB  - Escherichia coli DNA-directed RNA polymerase is shown to contain a novel
      phosphorolytic error correction activity which removes erroneous nucleotides, as
      rNDPs, from the 3'-end of the growing transcript. The activity we describe is
      biochemically similar to polynucleotide phosphorylase (PNP), yet in contrast to
      PNP is activated by Mn2+. We demonstrate that the activity, which is mediated by
      Pi, is dependent on the presence of an incorrectly incorporated nucleotide at the
      leading 3'-end of the transcript. The correction activity we describe exhibits a
      4 x 10(4)-fold preference for the excision of incorrect nucleotides from the
      transcript. These findings suggest the possibility that RNA phosphorolysis may
      play a critical role in the process of transcriptional proofreading.

PMID- 7520116
TI  - Replication control of plasmid R1: disruption of an inhibitory RNA structure that
      sequesters the repA ribosome-binding site permits tap-independent RepA synthesis.
AB  - The replication frequency of plasmid R1 is controlled by an antisense RNA, CopA,
      that inhibits the synthesis of the replication initiator protein, RepA, at the
      post-transcriptional level. This inhibition is indirect and affects translation
      of a leader peptide reading frame (tap). Translation of tap is required for repA
      translation (Blomberg et al., 1992). Here we asked whether an RNA stem-loop
      sequestering the repA ribosome-binding site blocks tap translation-independent
      repA expression. Destabilization of this structure resulted in tap-independent
      RepA synthesis, concomitant with a loss of CopA-mediated inhibition; thus, CopA
      acts at the level of tap translation. Structure probing of RepA mRNAs confirmed
      that the introduced mutations induced a local destabilization in the repA
      ribosome-binding site stem-loop. An increased spacing between the repA Shine
      Dalgarno region and the start codon permitted even higher repA expression. In
      Incl alpha/IncB plasmids, an RNA pseudoknot acts as an activator for rep
      translation. We suggest that the regulatory pathway in plasmid R1 does not
      involve an activator RNA pseudoknot.

PMID- 7520118
TI  - Determinations of restriction fragment length polymorphism in bacteria using
      ribosomal RNA genes.

PMID- 7520117
TI  - Microevolution within a clonal population of pathogenic bacteria: recombination,
      gene duplication and horizontal genetic exchange in the opa gene family of
      Neisseria meningitidis.
AB  - Opacity (Opa) proteins are a family of antigenically variable outer-membrane
      proteins of Neisseria meningitidis. Even among clonally related epidemic
      meningococcal isolates, there is greater variation of Opa protein expression than
      can be accounted for by the opa gene repertoire of any individual strain. We
      characterized the opa genes of eight closely related isolates of serogroup A N.
      meningitidis (subgroup IV-1) from a recent meningitis epidemic in West Africa.
      DNA sequence analysis and Southern blot experiments indicated that changes
      occurred in the opa genes of these bacteria as they spread through the human
      population, over a relatively short period of time. Such changes in one or a few
      loci within a clonal population are referred to as microevolution. The
      distribution of sequences present in hypervariable (HV) regions of the opa genes
      suggests that duplication of all or part of opa genes into other opa loci changed
      the repertoire of Opa proteins that could be expressed. Additional variability in
      this gene family appears to have been introduced by horizontal exchange of opa
      sequences from other meningococcal strains and from Neisseria gonorrhoeae. These
      results indicate that processes of recombination and genetic exchange contributed
      to variability in major surface antigens of this clonal population of pathogenic
      bacteria.

PMID- 7520119
TI  - Phylogenetic identification of uncultured pathogens using ribosomal RNA
      sequences.

PMID- 7520120
TI  - Assays for hyaluronidase activity.

PMID- 7520121
TI  - Assays of hemolytic toxins.
AB  - The ability to produce a cytolytic toxin contributes to the success of many
      organisms in a particular niche by such diverse means as lysis of a
      phagolysosomal membrane of the macrophage by hemolysin from the intracellular
      parasite Trypanosoma cruzi, disruption of leukocyte activity by the Escherichia
      coli hemolysin, and destruction of invading bacteria by hemolysin from the
      annelid Glycera dibranchiata. The relative contribution of erythrocyte lysis to
      survival of the cytolysin producer is still under investigation. Nevertheless,
      the hemolytic phenotype is both a powerful tool for identifying novel cytolysins
      and a convenient marker for studying cytolytic activity in established toxins.

PMID- 7520122
TI  - Use of lipid bilayer membranes to detect pore formation by toxins.

PMID- 7520123
TI  - The cloned neurotensin receptor mediates cyclic GMP formation when coexpressed
      with nitric oxide synthase cDNA.
AB  - Rat neurotensin (NT) receptor (NTR) cDNA was subcloned into the pRC-CMV
      expression vector and transfected into 293 cells, and cellular clones that stably
      expressed the NTR were isolated and characterized. [3H]NT binding to membranes
      prepared from the NTR cDNA-transfected cells displayed specificity and
      saturability, with an apparent Kd of 1.25 nM and a Bmax of 43.4 pmol/mg of
      protein (approximately 3.5 x 10(6) binding sites/cell). NT stimulated an increase
      in [3H]inositol phosphate levels in the NTR-expressing cells up to 2500% of basal
      levels. The response was time and dose dependent, with an EC50 of 10.4 nM. NT
      also stimulated cAMP formation in these cells, with an EC50 of 27.0 nM. In
      addition, NT evoked an increase in the level of intracellular calcium.
      Approximately 60% of the calcium rise was attributable to the release of
      intracellular stores and 40% was attributable to calcium influx. Although NTR
      occupancy has been shown to stimulate cGMP formation in several brain
      preparations and cell lines, NT was unable to mediate cGMP synthesis in the NTR
      expressing 293 cells. We found that 293 cells have guanylate cyclase activity but
      have undetectable levels of nitric oxide synthase (NOS) activity. Because it was
      possible that the production of nitric oxide is required as the mediator of NT
      induced cGMP synthesis, we subcloned NOS cDNA into the pCEP4 expression vector
      and transiently expressed it in the NTR cells. We report that NT increased cGMP
      levels up to 375% of basal levels when NOS cDNA was coexpressed and that the
      increase was completely inhibited by the NOS inhibitor N omega-nitro-L-arginine.
      NT-induced cGMP accumulation was time and dose dependent, with an EC50 of 1.7 nM.
      To our knowledge, this is the first report of NT mediating cGMP formation with a
      cloned receptor and the first evidence that NT-induced cGMP accumulation requires
      the production of nitric oxide.

PMID- 7520124
TI  - 3 alpha-Hydroxy-5 beta-pregnan-20-one sulfate: a negative modulator of the NMDA
      induced current in cultured neurons.
AB  - We have shown previously that the neurosteroid pregnenolone sulfate acts as a
      positive allosteric modulator at the N-methyl-D-aspartate (NMDA) receptor while
      inhibiting the kainate, the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
      (AMPA), the glycine, and the gamma-aminobutyric acid (GABA) responses of chick
      spinal cord neurons. Here, we report that 3 alpha-hydroxy-5 beta-pregnan-20-one
      sulfate (5 beta 3 alpha S), a sulfated form of naturally occurring 5 beta 3
      alpha, inhibits both the NMDA and the non-NMDA receptor-mediated responses as
      measured by whole cell voltage clamp recordings. 100 microM 5 beta 3 alpha S
      rapidly and reversibly inhibits the response to 30 microM NMDA by 66%, 50 microM
      kainate by 37%, and 25 microM AMPA by 29%. Application of 50 microM nonsulfated 5
      beta 3 alpha does not produce any significant effect on the NMDA response,
      demonstrating that the sulfate moiety is important for the effect of 5 beta 3
      alpha S on the NMDA response. The effect of 5 beta 3 alpha S on the NMDA response
      is concentration dependent, with an EC50 of 62 microM. 5 beta 3 alpha S reduces
      the maximum NMDA response with little effect on the NMDA EC50, indicating that
      antagonism of the NMDA response by 5 beta 3 alpha S is noncompetitive. The fact
      that 5 beta 3 alpha S inhibition of the NMDA response is neither agonist nor
      voltage dependent demonstrates that 5 beta 3 alpha S does not act as an open
      channel blocker. Furthermore, inhibition of the NMDA response by 5 beta 3 alpha S
      is not reduced by the addition of a maximal concentration (10 microM) of glycine,
      indicating that 5 beta 3 alpha S does not act via the glycine recognition site.
      The inhibitory action of 5 beta 3 alpha S on the NMDA and non-NMDA receptors may
      provide a basis for inhibiting glutamate receptor-induced seizures and
      excitotoxic cell death.

PMID- 7520125
TI  - 9-Aminoacridines act at a site different from that for Mg2+ in blockade of the N
      methyl-D-aspartate receptor channel.
AB  - The effects of alkylene bis-9,9'-aminoacridines and 1,2,3,4-tetrahydro-9
      aminoacridine (THA) were studied on single-channel currents activated by N-methyl
      D-aspartate (NMDA) in outside-out patches from cultured rat hippocampal neurons.
      These compounds reduced the channel open times with concentration and voltage
      dependence, which was consistent with an open-channel blockade mechanism of
      action. In nominally Mg(2+)-free solutions, the forward blocking rate constants
      for 1,2-propane-bis-9,9'-aminoacridine, 1,4-butane-9,9'-aminoacridine, and THA
      were 1.1 x 10(8), 1.4 x 10(8), and 3.5 x 10(7) M-1 sec-1, respectively, at a
      holding potential of -80 mV. The unblocking rate constants for the bis-9
      aminoacridines were similar and in the range of 7 sec-1, whereas THA had an
      unblocking rate constant of approximately 6.2 x 10(3) sec-1. In the presence of
      Mg2+ (approximately 5 microM), the predictions of the model for open-channel
      blockade by the 9-aminoacridines were invalid, because the relationships between
      the channel lifetimes and 9-aminoacridine concentrations were not linear. The
      effects of Mg2+ (approximately 0-50 microM) on the open-channel blockade of the
      NMDA receptor by the 9-aminoacridines were evaluated further by measuring the
      burst times in the presence of 1,2-propane-bis-9,9'-aminoacridine (5 microM). The
      results suggested that the interactions of 9-aminoacridines and Mg2+ with the ion
      channel of the NMDA receptor were not mutually exclusive. Simultaneous occupancy
      of the NMDA receptor ion channel by Mg2+ and a channel-blocking organic cation
      could be a common mechanism of channel blockade for this receptor under
      physiological conditions.

PMID- 7520126
TI  - Cooperative interactions between general anesthetics and QX-222 within the pore
      of the acetylcholine receptor ion channel.
AB  - To test the hypothesis that general anesthetics block nicotinic acetylcholine
      receptor channels by binding within the pore of the channel, we looked for
      competitive interactions between ether and QX-222 at the single channel current
      level. Experiments were performed on outside-out patches excised from BC3H-1
      cells. QX-222 causes channels to flicker as it repeatedly binds within the pore
      of the channel and blocks the flow of current through the channel. Ether reduces
      the apparent unitary conductance of the channel. This effect of ether may be due
      to frequent, short-lived, unresolved, blockages of the channel. When both ether
      and QX-222 are applied, the effects of both drugs are seen on single channels.
      However, the duration of QX-222 blocking events are longer when ether is present;
      the duration of block is 0.89 +/- 0.06 ms with 30 microM QX-222 alone and 2.23 +/
      0.37 ms with 30 microM QX-222 + 20 mM ether (n = 5 +/- S.D.; -100 mV). Similar
      results are obtained when butanol is used in place of ether. We conclude that
      ether and QX-222 do not compete for a common binding site. Conversely, ether
      decreases the dissociation rate of QX-222. The simplest interpretation of these
      data is that the binding sites for ether and the aromatic moiety of QX-222 are
      distinct but close to each other; when ether is bound to its site, the binding of
      QX-222 is stabilized. We cannot, however, discount the possibility that ether
      stabilizes QX-222 by binding to a remote site and allosterically modifying the
      pore of the channel.

PMID- 7520128
TI  - Alternatively polyadenylated vasoactive intestinal peptide mRNAs are
      differentially regulated at the level of stability.
AB  - The role of cis-acting destabilizing RNA sequences in the determination of
      endocrine gene expression has been investigated using a novel paradigm, in which
      the differential regulation of two alternatively polyadenylated RNA transcripts
      may be observed both in vivo and in vitro. In the rat anterior pituitary gland in
      vivo, we have shown that, after the termination of an estrogen stimulus, a 1.7
      kilobase (kb) vasoactive intestinal peptide (VIP) RNA containing an extensive 3'
      untranslated region (UTR), is preferentially down-regulated with respect to a 1.0
      kb VIP transcript that is uniquely abundant in this tissue. Differential
      regulation of the anterior pituitary VIP transcripts can be modeled in an explant
      culture system in which we defined both transcriptional and posttranscriptional
      phases of VIP gene regulation in vitro, and showed that selective down-regulation
      of the 1.7-kb transcript is posttranscriptional. Inhibitors of transcription and
      translation have also allowed us to show in vitro that differential regulation of
      VIP transcripts occurs through an active process that appears to involve the
      synthesis of a labile, destabilizing factor. In order to confirm the role of RNA
      destabilization as the primary mechanism of differential posttranscriptional
      regulation, we have also performed cell-free stability assays in which explant
      extracts were incubated with 32P-labeled run-off transcripts corresponding to the
      two alternatively polyadenylated VIP RNAs. The resultant estimates of RNA half
      life showed significantly lower values for the synthetic VIP transcript
      containing the 3'-UTR. Our findings demonstrate the presence of functional
      destabilizing sequences in the 3'-UTR of the rat VIP RNA which appear to act in
      the physiological control of VIP gene expression.

PMID- 7520127
TI  - Regulation of insulin receptor, insulin receptor substrate-1 and
      phosphatidylinositol 3-kinase in 3T3-F442A adipocytes. Effects of
      differentiation, insulin, and dexamethasone.
AB  - Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in
      phosphorylation of its cytosolic substrate insulin receptor substrate 1 (IRS-1),
      which in turn associates with and activates the enzyme phosphatidylinositol 3
      kinase (PI 3-kinase). In the present study we have examined these three initial
      steps in insulin action during the differentiation of 3T3-F442A adipocytes and
      after treatment with dexamethasone or insulin. The differentiation of 3T3-F442A
      cells was characterized by a 13-fold increase in insulin receptor protein, a 9
      fold increase in IRS-1, and a 10- and 4.5-fold increase in their insulin
      stimulated phosphorylation, respectively. The mRNA expression of these two
      proteins showed a similar 8-fold increase during differentiation. In addition
      there was a 3.5-fold increase in PI 3-kinase protein [85 kilodalton (kDa)
      subunit] and a 16-fold increase in IRS-1-associated PI 3-kinase activity between
      day 0 and day 8 of differentiation. Dexamethasone (1 microM) treatment of
      differentiated cells induced a further 48% (P < 0.05) increase in insulin
      receptor level, but the autophosphorylation of the receptor was decreased by 31
      +/- 1% (P < 0.02). At the same time there was a decrease by 56 +/- 4% (P < 0.005)
      in IRS-1 protein and by 31 +/- 1% (P < 0.001) in IRS-1 phosphorylation. The
      expression of insulin receptor mRNA was unchanged, but the expression of IRS-1
      mRNA was decreased by approximately 75% after dexamethasone. By contrast,
      dexamethasone induced a 69% increase in the level of PI 3-kinase as determined by
      immunoblotting. The combined effect of decreased IRS-1 phosphorylation and
      increased PI 3-kinase protein was a minimal change (15% decrease) in the
      association/activation between IRS-1 and PI 3-kinase. Chronic treatment with 100
      nM insulin induced a time- and dose-dependent decrease in insulin receptor and
      IRS-1 protein levels reaching a nadir of 34 +/- 5% (P < 0.005) and 39 +/- 5% (P <
      0.01) of control levels after 24 h, respectively. There was an even more marked
      decrease in the phosphorylation level of these proteins. Chronic insulin
      treatment also produced a 30% decrease in PI 3-kinase protein levels and a
      approximately 50% decrease in the association/activation between IRS-1/PI 3
      kinase. The expression of insulin receptor and IRS-1 mRNA was unchanged during
      chronic insulin treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7520129
TI  - Induction of fetal hemoglobin in the presence of increased 3-hydroxybutyric acid
      associated with beta-ketothiolase deficiency.

PMID- 7520130
TI  - Differential effects of the novel analgesic, S 12813-4, on the spinal release of
      substance P- and calcitonin gene-related peptide-like materials in the rat.
AB  - The possible inhibitory control by the novel analgesic S 12813-4 (3-(2-(4
      phenylpiperazine-1-yl)-ethyl)-2-oxo-2,3- dihydrooxazolo(b)pyridine) of spinal
      neurones containing substance P (SP) and/or calcitonin gene-related peptide
      (CGRP) was assessed in vitro and in vivo in the rat. S 12813-4 (10 nM-0.1 mM) did
      not affect the spinal release of CGRP-like material (CGRPLM) but inhibited in a
      concentration dependent manner the K(+)-evoked overflow of SP-like material
      (SPLM) from slices of the dorsal half of the rat lumbar enlargement. The
      inhibitory effect of 10 microM S 12813-4 on SPLM release was not additive with
      that of Na (0.1 mM), and could be prevented by the alpha 2-adrenoceptor
      antagonist idazoxan (10 microM). Similarly, idazoxan (10 microM) suppressed the
      inhibition by intrathecally administered S 12813-4 (10 microM) of the spinal
      outflow of SPLM in halothane anaesthetized rats whose intrathecal space was
      perfused with an artificial cerebrospinal fluid. These data suggest that the
      analgesic effect of S 12813-4 might involve some alpha 2-adrenoreceptor-mediated
      control of SPLM release within the spinal cord. Whether this control concerns SP
      containing primary afferent fibres (presynaptic inhibition) or SP-containing
      interneurones and/or bulbo-spinal SP-ergic pathways (postsynaptic inhibition)
      deserves further investigations.

PMID- 7520131
TI  - Serotonin protects C6 glioma cells from glutamate toxicity.
AB  - It was recently shown that addition of L-glutamate in millimolar amounts to a
      culture of C6 glioma cells induced cell death within 24 h. The mechanism for
      glutamate toxicity in the C6 glioma cells is linked to the inhibition of cystine
      uptake, leading to glutathione depletion through the cystine/glutamate antiporter
      (Xc) system. In the present study, neurotransmitters, whose receptors were
      localized on the glioma (glial) cells, were evaluated for their ability to
      protect C6 cells from glutamate toxicity through this amino acid antiporter.
      Among them, only 100 microM serotonin suppressed cell death by glutamate in a
      constant co-existence culture. The suppressive dose of serotonin was relatively
      low and the half-effective dose was about 35 microM. 8-Hydroxy-2-(DL-n
      propylamino)tetralin, a specific serotonin1A agonist, showed a comparable
      suppression to glutamate damage, while 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane, a specific serotonin2 agonist, and quipazine, a non-selective
      serotonin1B agonist, did not suppress it. Furthermore, propranolol and pindolol
      significantly blocked the serotonin effect, but spiperone, mianserin and
      ketanserin did not block it. These results strongly indicate that this protective
      action of serotonin to glutamate toxicity was receptor (serotonin1A) mediated.
      Serotonin did not protect the C6 cells from glutathione depletion by glutamate.
      The cellular level of glutathione was depleted even under the co-existence of
      serotonin and glutamate. Serotonin induced a significant inhibition of lipid
      peroxide accumulation in the C6 glioma cells to glutamate exposure and the low
      rate of lipid peroxide accumulation was controlled.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7520133
TI  - Morphological properties and projections of electrophysiologically characterized
      neurons in the guinea-pig submucosal plexus.
AB  - Intracellular recordings were made from 73 guinea-pig submucosal neurons using
      neurobiotin-filled microelectrodes; subsequently, neuropeptide immunoreactivity,
      morphology and nerve fibre projections were determined. Five distinct groups of
      cells could be distinguished: S cells with inhibitory input (61%), S cells
      without inhibitory input (19%), AH cells (8%), S-AH cells (5%), and glial
      networks. S cells with inhibitory input were immunoreactive for vasoactive
      intestinal polypeptide and showed Dogiel Type III morphology with the axon
      branching and coursing through two to 12 ganglia; varicosities and tufts of
      varicosities were observed surrounding other cell bodies as well as over blood
      vessels. S cells without inhibitory input primarily were immunoreactive for
      neuropeptide Y; they also showed Dogiel Type III morphology and similar, though
      shorter, axonal projections and varicose features surrounding other neurons. AH
      cells, which most likely contained substance P, lacked synaptic input and
      exhibited Dogiel Type II morphology; they branched more extensively than S cells
      and also formed varicose tufts within other ganglia. S-AH cells combined
      electrophysiological properties of S cells with inhibitory input and AH cells and
      did not show consistent morphological or histochemical characteristics. Typical
      glial networks were observed; in addition, on two occasions unusual networks of
      dye and electrical coupling between S cells without inhibitory input and a glial
      complex were observed. These results suggest that vasoactive intestinal
      polypeptide-containing S cells may act as interneurons which mediate a slow
      excitatory synaptic potential; that neuropeptide Y-containing S cells, which are
      known to be cholinergic, may play a role as cholinergic interneurons mediating
      the nicotinic fast excitatory synaptic potential; and that AH neurons also may
      provide cholinergic innervation to other submucosal neurons in addition to their
      previously described dual projections into mucosa and myenteric plexus.

PMID- 7520132
TI  - The effect of experimental ischaemia and excitatory amino acid agonists on the
      GABA and serotonin immunoreactivities in the rabbit retina.
AB  - The aim of the described experiments was to use immunohistochemistry to visualize
      the release of GABA from specific retinal amacrine cells following ischaemia and
      to establish the involvement of defined glutamatergic receptors. In initial
      experiments, rabbit retinas were exposed in vitro to excitatory amino acid
      agonists alone or in combination with a putative antagonist, or in physiological
      solution lacking oxygen and glucose, or in solution containing potassium cyanide
      for 45 min at 37 degrees C. The nature of the GABA immunoreactivity was then
      examined by immunohistochemistry. In other in vitro experiments, retinas were
      first allowed to accumulate exogenous serotonin before exposing the tissues to
      the combinations as described. These tissues were then processed
      immunohistochemically for the localization of serotonin. In yet other
      experiments, the intraocular pressure of a rabbit's eye was raised to about 110
      mmHg for 60 min and a reperfusion time of 45 min allowed before dissecting the
      retina and processing for the localization of GABA immunoreactivity. The other
      eye served as a control. Of the excitatory amino acid agonists tested, only N
      methyl-D-aspartate, kainate and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid caused a change in the GABA immunoreactivity. The N
      methyl-D-aspartate effect was specifically antagonized by dizocilpine maleate,
      dextromethorphan and memantine, and was characterized by a reduction in the
      number of GABA-immunoreactive perikarya. The GABA "staining" in the inner
      plexiform layer also appeared as four clear bands. The alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid- and kainate-induced effects were both
      antagonized by 6-cyano-2,3-dihydroxy-7-nitroquinoxaline-2,3-dione and partially
      by kynurenic acid at the concentrations used. Here, the amount of GABA-positive
      perikarya was greatly reduced and three immunoreactive bands appeared in the
      inner plexiform layer. However, for low concentrations of alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid four GABA-immunoreactive bands could be
      identified in the inner plexiform layer. The normal GABA immunoreactivity of the
      inner plexiform layer also appeared to be in defined bands in retinas which
      received an ischaemic insult either by reducing the availability of glucose and
      oxygen, exposing the tissue to potassium cyanide or raising the intraocular
      pressure of an eye. In these cases the number of GABA-positive perikarya was also
      reduced. Only alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and
      kainate of the excitatory amino acid agonists tested caused a release of
      serotonin and this process was antagonized by 6-cyano-2,3-dihydroxy-7
      nitroquinoxaline-2,3-dione and partially by kynurenic acid.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7520134
TI  - Differences in the regional and cellular localization of c-fos messenger RNA
      induced by amphetamine, cocaine and caffeine in the rat.
AB  - Male rats were treated i.p. with either 5 mg/kg amphetamine, 3 and 30 mg/kg
      cocaine or 100 mg/kg caffeine and killed after 30 min. Brains were sectioned and
      processed for radioactive in situ hybridization histochemistry for the labelling
      of either c-fos, enkephalin, substance P, neurokinin B, choline
      acetyltransferase, somatostatin or adenosine A2A receptor messenger RNA. The
      distribution of c-fos messenger RNA was investigated both at the regional level
      using film autoradiography, and at the cellular level using emulsion
      autoradiography. All drug treatments except 3 mg/kg cocaine induced an increased
      level of c-fos messenger RNA in cells that had a neuron-like morphology. The
      cells that contained the c-fos messenger RNA were identified by making pairs of 5
      microns sections in which one section was processed for c-fos messenger RNA and
      the other was processed for one of the other messenger RNA species. After
      amphetamine treatment, only some 10% of the cells in the striatum were labelled,
      and to a variable extent. Instead there was prominent labelling of a band in the
      cortex that runs parallel to the cortical surface. There was also a moderate
      degree of labelling in the nucleus accumbens. c-fos-positive cells were substance
      P-positive and negative for enkephalin or A2A receptor messenger RNA. Cocaine (30
      mg/kg) induced a modest labelling in the caudate-putamen, as well as in the
      accumbens. With cocaine treatment (30 mg/kg), about 30% of striatal neuron-like
      cells were c-fos labelled. Most c-fos-positive cells were substance P-positive,
      but none of the c-fos-positive cells were enkephalin-positive or A2A-receptor
      positive. Cocaine (3 mg/kg) had no significant effect on c-fos. Caffeine gave
      rise to a strong hybridization signal in the caudate-putamen, particularly the
      dorsolateral part. No other region examined differed significantly from control.
      With caffeine treatment, about 73% of neuron-like cells were c-fos labelled in
      the lateral striatum, but labelling was much less pronounced in the medial part
      or in the accumbens. c-fos-labelled cells were found in enkephalin-positive and
      enkephalin-negative, substance P-positive and substance P-negative, neurokinin B
      positive and neurokinin B-negative groups. No choline acetyltransferase-positive
      or somatostatin-positive cells were found that were also c-fos-positive with any
      of the treatments. We conclude that each of the different CNS stimulant drugs
      induces a highly specific pattern of c-fos messenger RNA.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7520135
TI  - Nitric oxide synthase expression reveals compartments of cerebellar granule cells
      and suggests a role for mossy fibers in their development.
AB  - The developmental expression and cellular distribution of nitric oxide synthase
      was investigated in the murine cerebellum and in cerebellar neurons developing
      under controlled in vitro conditions. Cerebellar granule cells expressed nitric
      oxide synthase only after migration to the internal granule cell layer.
      Initially, the nascent internal granule cell layer throughout the cerebellum
      stained uniformly for nitric oxide synthase, but during the second postnatal
      week, a pattern emerged consisting of clusters of heavily stained granule cells
      separated by areas of unstained granule cells. This pattern persisted into
      adulthood. There was a close temporal correlation between innervation of the
      granule cell layer by mossy fibers and the emergence of granule cell compartments
      as defined by levels of nitric oxide synthase expression. Granule cells in
      dissociated cultures derived from cerebellar anlagen prior to mossy fiber
      innervation also express nitric oxide synthase. The time-course of nitric oxide
      expression was independent of electrical activity of the neuronal network forming
      in vitro. However, suppression of spontaneous electrical activity resulted in
      enhanced nitric oxide synthase expression. These findings indicate that granule
      cell precursors are endowed with an intrinsic program which regulates nitric
      oxide synthase induction and which is executed independently of correct
      positional cues. The data also suggest that electrical activity of ingrowing
      mossy fibers down regulates nitric oxide synthase expression and plays an
      important role in the generation of granule cell compartments. These compartments
      may contribute to the functional organization of the cerebellar cortex.

PMID- 7520136
TI  - NADPH-diaphorase activity in activated astrocytes represents inducible nitric
      oxide synthase.
AB  - In paraformaldehyde-fixed sections of healthy brain, glial cells at the light
      microscope level do not contain measurable levels of NADPH-diaphorase. However,
      after a variety of lesions in the mouse brain, some reactive astrocytes express
      varying amounts of this enzyme. Following stab wounds, activated astrocytes or
      related glial cells surrounding the lesion, contained moderate to high levels of
      NADPH-diaphorase in the cerebellum, midbrain, thalamus, striatum, hippocampal
      formation and neocortex. Double-labelling experiments confirmed that this
      corresponds to an inducible form of nitric oxide synthase, similar to that found
      in activated macrophages. Within the lesion there were large numbers of
      macrophages which also contained NADPH-diaphorase. After 10 min of global hypoxic
      ischaemia, some reactive astrocytes also contained NADPH-diaphorase. These cells
      were confined to the dorsal part of the hippocampal formation (the dentate fascia
      and CA1 areas) and to the anterolateral striatum. More focal ischaemic damage,
      produced by dividing an arterial branch, also produced a rim of reactive
      astrocytes containing NADPH-diaphorase, that surrounded the area of necrosis. Low
      levels of NADPH-diaphorase were induced within one day of a stab wound and the
      enzyme activity reached near maximal levels by two days postlesion. Moderate
      NADPH-diaphorase activity was still present at 63 days postlesion, but only a
      small number of astrocytes were stained in the immediate vicinity of the lesion.
      These experiments confirm that NADPH-diaphorase activity represents inducible
      nitric oxide synthase in activated astrocytes and probably in inflammatory
      macrophages. We conclude that a high proportion of activated astrocytes and a
      small proportion of invading macrophages are induced to express moderate to high
      levels of nitric oxide synthase following neuronal damage. Our results indicate
      that following a variety of lesions reactive astrocytes are synthesizing
      significant levels of nitric oxide within 24 h. This nitric oxide may be involved
      in modulating the likelihood of epileptic seizures.

PMID- 7520137
TI  - 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline protects against both AMPA
      and kainate-induced lesions in rat striatum in vivo.
AB  - In the present work we have tested the neuroprotective effect of 2,3-dihydroxy-6
      nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) on the excitotoxic damage induced by
      the injection of several glutamate receptor agonists into the rat striatum. NBQX
      was co-injected with each of the agonists studied (1 microliter) in the striatum
      and damage was assessed by the determination of both glutamate decarboxylase and
      choline acetyltransferase activities in striatal homogenates, five days after the
      lesion. Additionally, animals were transcardially perfused with 0.9% saline/4%
      paraformaldehyde and brain coronal sections were stained with Cresyl Violet for
      histological analysis. Our results show that NBQX (25 nmol) did not protect
      against the damage induced by the intrastriatal injection of 200 nmol quinolinic
      acid monitored by either choline acetyltransferase or glutamate decarboxylase
      activity. In contrast, the same concentration of NBQX partially protected against
      200 nmol N-methyl-D-aspartate induced damage; this protection was more notable as
      detected by changes in choline acetyltransferase activity. When non-N-methyl-D
      aspartate receptor agonists were used as excitotoxins, coinjection of NBQX (25
      nmol) resulted in a notable protection against both alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionate (AMPA, 40 nmol) and kainate (10 nmol) induced
      neurodegeneration. At this concentration, protection was slightly better in AMPA
      injected animals (71% protection averaged from choline acetyltransferase and
      glutamate decarboxylase enzyme activities) as compared to kainate-injected
      animals (47.5% protection). When a higher concentration of NBQX was tested (40
      nmol) the protection against kainate improved to 65% while that against AMPA
      remained constant (64% protection).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520139
TI  - Neuropeptides and interleukin-6 in human joint inflammation relationship between
      intraarticular substance P and interleukin-6 concentrations.
AB  - Plasma and synovial fluid concentrations of interleukin-6 (IL-6), using an enzyme
      linked immunosorbent assay, as well as immunoreactive levels of calcitonin gene
      related peptide (CGRP), substance P and vasoactive intestinal peptide (VIP) were
      measured in 18 patients with rheumatoid arthritis and 20 with osteoarthritis of
      the knee. The concentrations of IL-6 were elevated in both plasma and synovial
      fluids from patients with rheumatoid arthritis whereas higher levels of substance
      P-, CGRP- and VIP-like immunoreactivities were found in the synovial fluid, but
      not in plasma, from patients with rheumatoid arthritis when compared with those
      in osteoarthritis. Furthermore, IL-6 and substance P levels in synovial fluid
      were significantly correlated both in rheumatoid arthritis and osteoarthritis
      patients. Our data seem to support the idea of an important role shared by
      neuropeptides and IL-6 in the pathogenesis of human inflammatory joint disease.

PMID- 7520138
TI  - Cholecystokinin corticostriatal pathway in the rat: evidence for bilateral origin
      from medial prefrontal cortical areas.
AB  - The anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to examine the
      organization of the projections to the striatum from medial prefrontal and
      frontal cortical areas in the rat with reference to their relation to
      cholecystokinin-like immunoreactivity in the striatum. Medial prefrontal cortical
      areas projected bilaterally, with an ipsilateral predominance, to the striatum.
      Most of the positive fibres were found in medial and ventral areas of the caudate
      putamen and in the nucleus accumbens. Labelled fibres formed distinct patch-like
      arrangements throughout the dorsomedial striatum, whereas more ventrally the
      fibres were densely packed and spread to lateral areas. Almost no fibres were
      found in the dorsolateral aspects of the caudate-putamen. Cholecystokinin-like
      immunoreactivity in the striatum was diffusely distributed in the medial aspects,
      in fine punctate elements as well as in patches of fibres. Overlapping of
      corticostriatal clusters of fibres, from medial prefrontal cortex, with
      cholecystokinin-immunoreactive patches was found at all rostrocaudal levels
      studied, but predominantly in rostral areas. The overlap was present both in the
      ipsilateral and the contralateral side. Often the cluster of corticostriatal
      fibres was completely and precisely overlaid by a cholecystokinin-immunoreactive
      patch. At more caudal planes the overlap was only partial and in some instances
      cholecystokinin-positive patches "avoided" zones of dense corticostriatal fibre
      terminations. Frontal cortex injections of tracer gave rise to a network of
      fibres in the lateral aspects of the striatum, sparing the medial areas. No
      overlap with cholecystokinin-immunoreactive patches was found in these cases.
      These results suggest that a large number of cholecystokinin-containing striatal
      fibres originate in medial prefrontal cortical areas.

PMID- 7520140
TI  - Golgi-like labeling of a single neuron recorded extracellularly.
AB  - We describe a novel and powerful extracellular method for the staining of a
      single neuron identified by electrophysiological criteria. This single-unit
      technique involves the use of glass micro-electrodes (tip diameter: 1.5-2.5
      microns) filled with a saline solution (NaCl; 0.5 M) containing 1.5% of biocytin
      or Neurobiotin. Once a neuron is recorded, isolated and identified, the tracer is
      delivered by anodal current pulses of a few nA. The cell must remain well
      isolated and alive during the ejection procedure to ensure optimal staining.
      Evidence is provided that the labeled neuron is actually the one that was
      recorded. Our simple method is reliable with a success rate exceeding 85%. The
      advantages and pitfalls are discussed. This single-unit labeling technique could
      further be combined with any other procedures ranging from biological to
      behavioral studies.

PMID- 7520141
TI  - Nitric oxide synthase immunoreactivity in the human ileocecal region.
AB  - The nitric oxide (NO) producing neurons in the human ileocecal region (pre
      junctional ileum, ileocecal and cecocolonic junctions, cecum and post-junctional
      colon) have been evaluated by immunocytochemistry. The percentage of NO synthase
      positive neurons was higher at the myenteric plexus than at the submucous plexus,
      independently of the levels examined. The inner portion of the circular muscle
      layer, except at the ileal level, was devoid of immunoreactive nerve fibers. Data
      obtained suggest that neuronal-released NO at the ileocecal region has a greater
      role in the relaxation of the muscle coat, except for the inner circular muscle
      layer, than in the regulation of blood flow, absorptive and secretory processes.

PMID- 7520142
TI  - Tunicamycin alters channel gating characteristics of junctional and
      extrajunctional acetylcholine receptors expressed in Xenopus oocytes.
AB  - The acute effects of tunicamycin on mouse junctional and extrajunctional
      acetylcholine receptors (AChRs) expressed in Xenopus oocytes, distinct from its
      ability to block N-glycosylation of the protein, was examined at the single
      channel level. Tunicamycin reduced the frequency of ACh-activated single channel
      openings and prolonged the mean channel open times of AChRs in a dose-dependent
      manner, without affecting inward conductances. Continuous application of ACh to
      both junctional and extrajunctional AChR channels very slowly decreased the
      number of channel opening events, and tunicamycin accelerated this process. These
      results suggest that tunicamycin alters channel gating kinetics and accelerates
      transition towards a desensitized state.

PMID- 7520143
TI  - Effects of an inhibitor for calcium/calmodulin-dependent protein phosphatase,
      calcineurin, on induction of long-term potentiation in rat visual cortex.
AB  - A role of Ca2+/calmodulin-dependent protein phosphatase (calcineurin) in
      induction of long-term potentiation (LTP) was investigated using its selective
      inhibitor, FK506, in visual cortical slices of young rats. Field potentials or
      excitatory postsynaptic potentials (EPSPs) to test stimulation of white matter
      were recorded extra- or intracellularly from layer 2/3, and tetanic stimulation
      (tetanus) was applied to the white matter at 5 Hz. During the application of
      FK506 (1 microM), short tetanus (6 s) which had rarely induced LTP in the normal
      medium, became effective in inducing LTP. Tetanus for 1 min in the presence of
      FK506 induced LTP with higher probability than in the normal medium. To test
      possible involvement of presynaptic mechanisms, paired pulses at 50 ms intervals
      were given to the white matter. The facilitation ratio of the second to first
      EPSPs was not significantly changed by FK506 and after the induction of LTP,
      suggesting that the action of FK506 may not be presynaptic. To confirm this,
      FK506 was injected directly into neurons through recording electrodes. In cases
      in which stable EPSPs were recorded, the probability of LTP induction became
      higher than that obtained with normal electrodes. These results suggest that
      calcineurin plays a role in processes antagonizing the induction of LTP in visual
      cortex.

PMID- 7520144
TI  - Axonal transport of actin and actin-binding proteins in the rat sciatic nerve.
AB  - Actin is one of the major cytoskeletal proteins carried in slow axonal transport.
      Since more than 50% of actin in the axon was recovered in the high-speed
      supernatant, we looked for G-actin-binding proteins in slow axonal transport. Two
      weeks after injection of L-[35S]methionine into the rat spinal cord (L3-L5),
      labeled proteins in the sciatic nerve were extracted and those with potential
      abilities to interact with G-actin were detected by two independent methods: (A)
      DNAase I affinity chromatography and (B) blot overlay with biotinylated actin. By
      method (A), a 68 kDa Ca(2+)-dependent binding protein and a 45 kDa Ca(2+)
      independent binding protein were detected. The 68 kDa protein was also a major
      protein binding to actin in method (B). The 68 kDa protein was identified with
      the Ca(2+)-dependent phospholipid binding protein annexin VI by two-dimensional
      electrophoresis and Western blotting. As annexin VI is a component of slow axonal
      transport, it does not seem to be bound to membranous organelles in the axon. Our
      results suggest that annexin VI may play a role in the control of actin assembly
      and membrane-microfilament interaction.

PMID- 7520146
TI  - Hypoperfusion of the iris and its consequences in anterior segment pigment
      dispersal syndrome.
AB  - The effects of changes in iris perfusion in anterior segment pigment dispersal
      syndrome (ASPDS) were examined by iris fluorescein angiography in 29 patients (20
      men and 9 women; mean age, 49 +/- 14 years; range, 29 to 77 years). All showed
      hypoperfusion, with mild to moderate microneovascularization. There was a
      significant relationship between the degree of hypoperfusion and pigment scatter
      (P < .05), and between the level of intraocular pressure (IOP) and angle
      pigmentation (P < .01). No statistically significant relation was found between
      hypoperfusion and iris leak, nor between the level of IOP and iris hypoplasia,
      hypoperfusion, leakage of dye, pigment scatter, or iris processes. These findings
      suggest that iris hypoplasia and hypoperfusion are the underlying causes of ASPDS
      with a congenital etiology.

PMID- 7520145
TI  - Benzoporphyrin derivative: a potent photosensitizer for photodynamic destruction
      of rabbit endometrium.
AB  - OBJECTIVES: To determine the optimal pharmacokinetic characteristics for
      photodynamic endometrial destruction using topically applied benzoporphyrin
      derivative and to evaluate long-term morphologic effects in a rabbit model.
      METHODS: Benzoporphyrin derivative pharmacokinetics were measured by analyzing
      frozen tissue sections 1.5-12 hours following topical administration.
      Photodynamic therapy was induced intraluminally 1.5 hours after drug application,
      and tissue morphology was evaluated by light and scanning electron microscopy 1
      and 4 weeks after treatment. RESULTS: The highest glandular and stromal
      fluorescence was observed 1.5 hours after topical administration. Relative
      fluorescence of the endometrial glands significantly exceeded that of stroma and
      myometrium mainly at 1.5 and 3 hours (P < .0001). Histology revealed persistent
      epithelial destruction with minimal regeneration. Stroma resembled scar tissue in
      the majority of sections. The bordering myometrium was loosened and invaded by
      connective tissue. CONCLUSION: Topically applied benzoporphyrin derivative can be
      used for highly effective, long-lasting photodynamic destruction of rabbit
      endometrium. However, optical dosimetry can vary, particularly in the rabbit
      model, and this appears to affect long-term reepithelialization.

PMID- 7520147
TI  - Central retinal vein occlusion, an investigation by color Doppler imaging. Blood
      velocity characteristics and prediction of iris neovascularization.
AB  - PURPOSE: To determine pulsatile blood velocities in the orbital vasculature in
      patients with central retinal vein occlusion (CRVO). METHODS: The ophthalmic
      artery, central retinal artery, and vein of 80 patients with CRVO and 95 control
      subjects were investigated by color Doppler imaging. The patients were examined
      by ophthalmoscopy, relative afferent pupillary measurement using cross-polarized
      filters, fundus fluorescein angiography, and electroretinography to estimate the
      degree of retinal ischemia. RESULTS: Blood flow velocities in the central retinal
      vein and artery of eyes with CRVO were significantly lower than in fellow eyes
      and controls. The measurements from the vein were most reduced and in some cases
      absent in those eyes with "ischemic" CRVO. Velocities also were reduced in the
      central retinal artery of the affected eyes, but no correlation with "ischemia"
      was detected. The risk of iris neovascularization in patients examined within 3
      months of onset of CRVO can be determined from the flow velocities with a high
      degree of predictability (75% sensitivity and 86% specificity). CONCLUSIONS:
      Blood velocity was reduced in the retinal circulation of patients with CRVO and
      reduced even further in the "ischemic" variant of CRVO. The results indicate that
      noninvasive color Doppler imaging could play a major part in the routine
      assessment of patients with CRVO within 3 months of onset.

PMID- 7520148
TI  - Visual results after surgical removal of subfoveal choroidal neovascular
      membranes.
AB  - PURPOSE: The authors report their experience with the surgical removal of
      subfoveal choroidal neovascularization. Correlations between preoperative
      characteristics and final postoperative visual acuity are explored. METHODS: A
      retrospective study of 159 consecutive patients was performed between February
      1990 and August 1993. Follow-up of 2 or more months was available for 147 eyes:
      presumed ocular histoplasmosis syndrome, 67 eyes; age-related macular
      degeneration, 41 eyes; myopia, 10 eyes; multifocal choroiditis, 9 eyes;
      idiopathic, 8 eyes; angioid streaks, 4 eyes; and miscellaneous, 8 eyes. RESULTS:
      Sixty-seven eyes had presumed ocular histoplasmosis syndrome: mean follow-up was
      10.5 months. Visual acuity was stable or improved in 56 (83%) eyes and 20/40 or
      greater in 21 (31%) eyes. Mean interval to best visual acuity was 3 months. A
      recurrence rate of 37% had no significant effect on final visual outcome (P =
      0.952). Forty-one eyes had age-related macular degeneration: mean follow-up was
      15 months. Visual acuity was improved in only five (12%) eyes and was 20/40 or
      greater in only two (5%) eyes. The interval to best visual acuity was 5 months. A
      recurrence rate of 27% had not significant effect on final visual outcome (P =
      0.31). The visual results and recurrence rates for eyes with less common
      disorders are presented. CONCLUSION: The surgical excision of subfoveal choroidal
      neovascularization may stabilize or improve visual acuity in selected cases.
      Patients with focal disorders of the retinal pigment epithelium-Bruch's membrane
      complex appear to have a better surgical outcome than those with diffuse disease.

PMID- 7520151
TI  - Release of nitric oxide during the experimental infection with Trypanosoma cruzi.
AB  - We analysed the production of nitric oxide (NO) intermediates by cells from
      BALB/c mice infected with either virulent (Tulahuen or RA) or avirulent (CA-1)
      strains of Trypanosoma cruzi. Peritoneal or spleen cells from mice infected with
      T. cruzi released NO when incubated without further stimuli. Cells from mice
      during the acute stage of infection accumulated higher levels of inducible NO
      synthase mRNA and produced both, before and after lypopolysaccharide stimulation,
      higher amounts of NO than cells from mice chronically infected with T. cruzi. NO
      synthesis showed similar kinetics in connection with all three strains of T.
      cruzi, but cells from mice inbred with the Tulahuen or RA strains released higher
      levels of IFN-gamma, an activator of the NO pathways, than cells from mice
      infected with the CA-1 strain. In vivo administration of L-Ng-monomethyl-L
      arginine (L-NMMA), a competitive inhibitor of NO synthase, increased the
      susceptibility of mice to T. cruzi. We conclude that infection with T. cruzi
      induces NO production, and suggest that NO plays a role in the resistance against
      the parasite.

PMID- 7520149
TI  - Instability at the W/c-kit locus in mice: analysis of melanocyte cell lines
      derived from reversion spots.
AB  - Mutations at the mouse W/c-kit locus have pleiotropic defects including impaired
      development of the melanocyte lineage. We have characterized the molecular basis
      of the Wei mutation. We show here that Wei is the result of a missense mutation
      in the ATP binding site domain of c-kit proto-oncogene which affects the tyrosine
      kinase function of the receptor. As a result, few melanoblasts survive during
      embryogenesis in heterozygous Wei/+ foetuses. Therefore the adult skin is partly
      devoid of differentiated pigmented cells giving rise to a mottled coat colour
      phenotype. However, three per cent of Wei/+ mice exhibit spots of wild-type
      pigmentation on the coat which is otherwise of mutant phenotype. Such areas are
      known as phenotypic reversions. To dissect the molecular events responsible for
      the phenotypic instability of the Wei mutation, we have isolated pure cultures of
      continuously proliferating melanocytes from two independent reversion spots.
      These melanocyte lines, designated Wei-R1 and Wei-R2, were shown to exhibit none
      of the characteristics associated with transformed melanocytes. We have used a
      polymorphic restriction site generated by the Wei mutation to show that both
      melanocyte lines are still heterozygous at the W focus. Furthermore, Wei-R1 and
      Wei-R2 melanocytes express both the mutated and the wild-type c-kit RNA. These
      results indicate that the somatic mutation events responsible for reversion spots
      are not necessarily associated with loss of heterozygosity at the W/c-kit locus.
      Together with previous data, this points to the fact that several mechanisms
      account for the coat colour reversion phenotype.

PMID- 7520150
TI  - Structural analysis of the human nov proto-oncogene and expression in Wilms
      tumor.
AB  - We have cloned and sequenced the nov gene (novH) which is the homolog of the
      chicken nov proto-oncogene overexpressed in avian nephroblastomas. The novH gene
      is highly conserved and encodes a putative IGF-binding protein similar to that of
      chicken. We report that relative to autologous normal kidney expression of novH
      is elevated in Wilms tumors containing predominantly stromal elements and is
      inversely correlated in these tumors to the expression of WT1. Our results
      suggest that the regulation of IGFII expression by WT1 and increase of novH in
      Wilms tumors might be interrelated and represent a key element in tumor
      development in human.

PMID- 7520152
TI  - Recognition of Giardia lamblia cyst-specific antigens by monoclonal antibodies.
AB  - Immunization of BALB/c mice with a sonicated extract of in vitro-generated
      Giardia lamblia cysts produced six cyst-specific monoclonal antibodies (MoAbs).
      Two MoAbs (8C5.C11 and 5A4.G6), which recognize proteinaceous cyst antigens, were
      selected for further study. In indirect immunofluorescence (IFA), MoAb 8C5.C11
      reacted with encystation-specific vesicles in trophozoites beginning 3 h after
      the induction of encystation in vitro. This MoAb also recognized cysts which
      began to appear at 12 h. In contrast, MoAb 5A4.G6 stained only cyst walls. In
      Western blots, both MoAbs also reacted with cyst antigens, but not trophozoite
      antigens. MoAb 8C5.C11 first recognized cyst antigen from 3 h encysting cultures,
      reacting with 26, 28, 42 and 46 kD bands. MoAb 5A4.G6 reacted with a 38 kD band,
      beginning with 12 h encysting cultures. When added to G. lamblia encysting
      cultures before the appearance of cysts (0 to 9 h) and in the presence of a
      source of complement, MoAb 8C5.C11 caused a significant reduction in the numbers
      of water-resistant cysts produced in vitro compared to the control. MoAb 5A4.G6
      did not affect in vitro encystation. These findings confirm the heterogeneity of
      cyst antigens, and also indicate that the process of encystation in vitro can be
      interrupted by antibodies and complement.

PMID- 7520154
TI  - Surface antigens of Litomosoides carinii microfilariae: agglutinating antibodies
      react with sheath components of 40 and 120 kilo Dalton molecular mass.
AB  - This study was conducted to identify surface antigens of the microfilarial sheath
      of Litomosoides carinii which are accessible to antibodies. Rabbit antisera were
      raised against the soluble and insoluble fractions of purified sheaths by
      extracting them with a buffer containing 2-mercaptoethanol and sodium
      dodecylsulphate. These sera and rabbit hyperimmune sera directed against
      homogenates of total microfilariae, mature (i.e. microfilariae liberating) female
      parasites and excretory-secretory products of adult females were able to
      agglutinate live and formaldehyde-fixed microfilariae. When the antisera directed
      against sheath constituents were administered to patently infected Mastomys
      coucha, the microfilaraemia of these animals was rapidly reduced and remained low
      for a period of 2-3 weeks. Antibodies specifically binding to the microfilarial
      surface were immunoaffinity-purified on formaldehyde-fixed microfilariae. The
      antibodies react with sheath antigens of 40 and 120 kDa molecular mass which are
      produced by the epithelium of the distal uterus of the mature female, secreted
      and attached to the surface of the sheaths. A 120 kDa antigen recognized by anti
      sheath surface antibodies was also detected in the excretory-secretory products
      of in vitro-cultured immature female L. carinii from day 30 post-infection
      onwards. In the excretory-secretory products of mature adult female parasites
      recovered on day 130 post-infection, this 120 kDa molecule was absent. However,
      material reacting with the antibody was detected in the stacking gel of SDS
      polyacrylamide gels. This finding may indicate that the basic units forming the
      120 kDa antigen of immature adults or microfilarial sheath surface antigens occur
      in a highly polymerized form in the excretory-secretory products of mature female
      parasites.

PMID- 7520153
TI  - Production and characterization of genus and species specific monoclonal
      antibodies against surface tegumental antigens of Schistosoma mekongi.
AB  - A panel of monoclonal antibodies (MoAbs) against freeze-thaw surface tegumental
      antigens of Schistosoma mekongi were produced from naturally infected BALB/c
      mice. In this study, we have characterized two MoAbs which have different
      antigenic specificity for S. mekongi, S. japonicum and S. mansoni. The target
      epitopes of these two hybridoma antibodies are contained in the M(r) 38 kDa
      (designated Sme 38) and M(r) 97 kDa (designated Sme 97) proteins of adult worms
      as analysed by immunoblotting. The Sme 38 epitope was genus-specific, since it is
      also detectable in S. japonicum and S. mansoni. The Sme 97 was not detected in S.
      japonicum and S. mansoni, therefore it is considered as species-specific epitope.
      Immunocytochemical analysis revealed the presence of Sme 38 epitope in the
      surface tegument, the tegumental cells lying underneath the muscle layer and gut
      surface. The Sme 97 epitope was detectable only in the surface tegumental area.

PMID- 7520155
TI  - [Extracorporeal immunostimulating effect of terrilytin and lysozyme in vibration
      injury].
AB  - In injection of allogeneic erythrocytes treated with terrilytin of lysozyme (LTE)
      the most marked effect was produced by LTE injection in vibration-exposed rats
      (VER). When the VER were given injections of various fractions (light, moderate,
      and heavy) of erythrocytes previously incubated with enzymes, the heavy LTE
      possessed a marked immunostimulating effect. However, the heavy erythrocyte
      fraction proved to cause a stronger effect when it was treated successively with
      terrilytin and lysozyme. It was established that injection of this fraction does
      not influence the production of immunosuppression factors, in VER, which are
      produced by splenic cells adhering to the plastic after the vibration action, but
      induced the production of the immunostimulating factor by VER cells which do not
      adhere to the plastic.

PMID- 7520156
TI  - [A method for staining ischemic neurons in the brain and spinal cord].

PMID- 7520157
TI  - Potassium single-channel properties in normal and Rous sarcoma virus-transformed
      chicken embryo fibroblasts.
AB  - Ion channels in normal and Rous sarcoma virus (RSV)-transformed chicken embryo
      fibroblasts (CEFs) were examined by using the patch-clamp technique. Three
      different types of ion channels were observed with single-channel conductances in
      symmetrical 140 mM KCl (with frequencies of occurrence in parentheses) of 186 pS
      (70%), 110 pS (10%), and 65 pS (20%), which are identical in normal and RSV
      transformed CEFs. The total channel density in both cell types is about 0.13 per
      micron2. All three types of channels are highly selective for K+ ions, they are
      Ca(2+)- and voltage-dependent, and they can be completely blocked by external
      tetraethylammonium (10 mM) in both normal and RSV-transformed cells. Some channel
      properties, however, are different in normal and RSV-transformed CEFs. The K186
      channel of normal CEFs is almost completely activated in the presence of about 1
      nM free internal Ca2+ and is insensitive to charybdotoxin (100 nM). In contrast,
      the K186 channel of RSV-transformed CEFs has an EC50 value for activation by
      internal Ca2+ of about 100 nM and is highly sensitive to charybdotoxin (IC50 = 9
      nM). In normal CEFs, the K186 channel activity starts at membrane potentials more
      positive than -50 mV and reaches a high open state probability of 0.94 at +50 mV.
      In RSV-transformed CEFs, the threshold of K186 channel activity is also -50 mV
      but the maximal open state probability is only 0.70 at +50 mV membrane potential.
      Averages of current traces of K186 channels show the typical features of the
      macroscopic K+ currents described previously for normal and RSV-transformed
      CEFs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520158
TI  - Activation of calcium influx by ATP and store depletion in primary cultures of
      renal proximal cells.
AB  - Cytoplasmic calcium changes and calcium influx evoked by adenosine triphosphate
      (ATP) were investigated in primary cultures of rabbit proximal convoluted tubule
      cells. Extracellular ATP (50 microM) induced a biphasic increase of [Ca2+]i
      measured with the calcium probe fura-2. In the early phase, the mobilization of
      intracellular pools resulted in a transient increase of [Ca2+]i from 106 +/- 11
      nM (n = 36) to 1059 +/- 115% (n = 29) of the resting level within 10 s. In the
      presence of external calcium, [Ca2+]i then decreased within 3 min to a sustained
      level (398 +/- 38%, n = 8). Measurements of fura-2 quenching by external
      manganese revealed that this phase was the result of an increased Ca2+ uptake,
      blocked by lanthanum (10 microM) and verapamil (100 microM) but not by the
      nifedipin (25 microM). Internal calcium store depletion by ATP induced an
      increased calcium influx through lanthanum- and verapamil-sensitive, nifedipin
      insensitive calcium channels, located on the apical membrane of the cells. As
      indicated by 86Rb+ efflux measurements, ATP activated a potassium efflux that was
      blocked by barium and Leiurus quinquestriatus hebraeus (LQH) venom (containing
      charybdotoxin) indicating the involvement of Ca(2+)-sensitive K+ channels.
      Moreover, in the presence of the LQH venom, the internal calcium stores were not
      replenished after being depleted by ATP. Our results indicate that an ATP-evoked
      hyperpolarization of the plasma membrane leads to increased Ca2+ influx, which
      facilitates the replenishment of the internal stores.

PMID- 7520159
TI  - A calcium-activated nonselective cationic channel in the basolateral membrane of
      outer hair cells of the guinea-pig cochlea.
AB  - The patch-clamp technique was used to investigate ion channels in the basolateral
      perilymph-facing membrane of freshly isolated outer hair cells (OHCs) from the
      guinea-pig cochlea. These sensory cells probably determine, via their motile
      activity, the fine tuning of sound frequencies and the high sensitivity of the
      inner ear. A Ca(2+)-activated nonselective cationic channel was found in excised
      inside-out membrane patches. The current/voltage relationship was linear with a
      unit conductance of 26.3 +/- 0.3 pS (n = 15) under symmetrical inger conditions.
      The channel excluded anions (PNa/PCl = 18 where PNa/PCl denotes the relative
      permeability of Na to Cl); it was equally permeant to the Na+ and K+ ions and
      exhibited a low permeability to N-methyl-D-glucamine and Ba2+ or Ca2+. Channel
      opening required a free Ca2+ concentration of about 10(-6) mol/l on the internal
      side of the membrane and the open probability (Po) was maximal at 10(-3) mol/l
      (Po = 0.72 +/- 0.06, n = 12). Adenosine 5'mono-, tri- and di-phosphate reduced Po
      to 29 +/- 14 (n = 5), 42 +/- 10 (n = 8) and 51 +/- 12 (n = 5) % of control Po,
      respectively, when they were added at a concentration of 10(-3) mol/l to the
      internal side. The channel was partially blocked by flufenamic acid (10(-4)
      mol/l) and 3',5'-dichlorodiphenylamine-2-carboxylic acid (DCDPC, 10(-5) mol/l).
      This type of channel, together with Ca(2+)-activated K+ channels, might
      participate in the control of membrane potential and modulate the motility of
      OHCs.

PMID- 7520160
TI  - Computerised image analysis in conjunction with fluorescence microscopy for the
      study of blood-brain barrier permeability in vivo.
AB  - The present paper describes a new method using computerised image analysis
      techniques for quantification of tracer extravasation over the blood-brain
      barrier as studied by intravital fluorescence microscopy. Cats were equipped with
      an open cranial window and continuously infused with fluorescein isothiocyanate
      labelled dextran (FITC-dextran, mol. wt. 70,000) to maintain a steady plasma
      concentration. Several cortical fields were recorded in each experiment and the
      images stored on video tape for off-line analysis. This procedure, which largely
      eliminates the superficial pial vasculature and allows extraction of the
      extravasation areas, consists of the following steps: (1) averaging of images,
      (2) software shading correction based on the original images for compensation of
      optical non-uniformity, (3) correction of displacement artefacts, (4) intensity
      adjustment, (5) generation of subtraction images by subtracting the first image
      of a series from the subsequent ones, (6) median filtering and thresholding, (7)
      a length recognition algorithm, and (8) elimination of small areas. Compared to
      the previously described method, step (2) has been newly developed and steps (4)
      and (8) added to enhance sensitivity for detecting tracer extravasation. The
      degree of extravasation in a cortical field at a given time point [E(f) value]
      was calculated as the mean intensity of the remaining pixels. The E(f) is a
      quantitative value computed by a fully automatised procedure which takes into
      account the number, as well as the size and intensity, of extravasation areas in
      a given cortical field. The E(f) values obtained at different times in a series
      of experiments were averaged to give the E(I) value.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7520161
TI  - A modified Apt test: a new look at an old test.
AB  - This study was designed to verify the applicability of a modified Apt test to
      blood stains on cloth and to determine whether the time of testing affects the
      accuracy of the results. We collected cord blood samples from full-term newborns
      (n = 35) and venous blood samples from gravid females (n = 30) and applied them
      in a random fashion with a cotton swab to standard cloth diapers. A blinded
      investigator applied an alkali solution to each stain and recorded either color
      change or no color change. In addition, a time course was performed by applying
      infant (n = 4) and adult (n = 4) samples to a cloth diaper at an initial starting
      point and varying the time of the performance of our modified test in intervals
      up to four hours. Thirty-four of 35 infant samples had no color change, and 29 of
      30 adult samples had an easily identified color change. The time course revealed
      that the samples were indistinguishable after 30 minutes had elapsed. Therefore,
      a modified Apt test can be used successfully to differentiate between adult and
      infant blood stains of nonstool origin, only if performed within 30 minutes of
      the time the stain is produced. This restriction is significant in the emergency
      department setting.

PMID- 7520162
TI  - Semi-automatic quantitation of nucleolar organizer regions in non-Hodgkin's
      lymphomas.
AB  - Nucleolar organizer regions may be useful in the diagnosis and classification of
      non-Hodgkin's lymphomas. In this study of 46 cases we applied morphometric
      analysis with quantitation of physical descriptors of the nuclear profile (area,
      perimeter) and both number and area of stained nucleolar organizers therein
      enclosed to a series of lymphomas and benign lymphoid infiltrates. While nuclear
      outlines were manually traced small organizer regions within the nuclear profiles
      were semi-automatically outlined by a thresholding procedure subjected to manual
      override. This results in determination of number, area and perimeter of
      organizer regions. Data were corrected for section thickness effects and a
      stereologic (three-dimensional) analysis was additionally performed. We found an
      increase in mean number and area of nucleolar organizers per nucleus in high
      grade lymphomas compared to benign infiltrates and lower grade lymphomas. Volume
      and thickness corrected data showed a decrease in organizer number with
      concomitant increase in organizer volume in the higher grade lymphomas.
      Multivariate analysis of the cases, previously classified histologically, showed
      that clear resolution could be obtained, on the basis of physical descriptors,
      both between as well as within groups of the three tumor grades.

PMID- 7520164
TI  - Differential immunohistochemical staining for retinoblastoma protein with the
      antibodies C15 and 1F8 in malignant mesothelioma.
AB  - The results of an immunohistochemical study of retinoblastoma protein in human
      non-neoplastic mesothelium (40 cases) and in malignant mesothelioma (36 cases)
      using the antibodies 1F8 and C15 are reported. All cases of malignant
      mesothelioma and non-neoplastic mesothelium were immunoreactive in more than 75%
      of the mesothelial cells for retinoblastoma protein with the C15 polyclonal
      antibody. Immunoreactivity for retinoblastoma protein was virtually absent with
      the 1F8 monoclonal body in neoplastic cells of all investigated mesotheliomas. In
      contrast, stromal cells in these mesotheliomas and all cases with non-neoplastic
      mesothelium were immunoreactive with the monoclonal antibody 1F8 in more than 75%
      of the cells. These findings may be indicative for the presence of an abnormal
      retinoblastoma protein in malignant mesothelioma lacking an epitope coded for
      between exons 21-27.

PMID- 7520163
TI  - Nucleolus organizer regions (AgNORs) in ductal mammary carcinoma. Comparison with
      classifications and prognosis.
AB  - The relevance of silver-stained NORs for classifications and prognosis was
      investigated in breast tissue. Paraffin sections from 137 cases of invasive
      ductal breast carcinomas and 12 cases with non-tumorous ductus epithelium as
      controls were stained according to a modified technique and analysed. From the
      cancer cases follow-up data up to 10 years (45 to 165 months) and in addition
      clinical, histological and several DNA distribution parameters were available.
      The nuclei and the silver grains were measured by means of a semiautomatic image
      analysis system. Significant differences in AgNOR features were found between
      controls and diploid tumors (p < or = 0.001), diploid and aneuploid tumors (p <
      or = 0.001), Bloom-Richardson-gradings I, II, and III (p < or = 0.001), and
      between the tumor cells from patients developing metastases within 5 years and
      those without (p < or = 0.002). The prognostic significance of AgNORs was
      estimated using Cox regression analysis. Four AgNOR features were correlated
      significantly with survival time. In a multivariate approach offering all
      parameters available an AgNOR parameter (CV of relative area AgNORs) ranked at
      the third position beyond the SD of DNA distribution and pTNM-staging.
      Considering the metastases-free interval of patients the same AgNOR feature
      showed an independent prognostic validity.

PMID- 7520165
TI  - Immunohistochemical profile of synovial sarcoma with emphasis on the epithelial
      type differentiation. A study of 49 primary tumours, recurrences and metastases.
AB  - The relationship between biphasic (BSS) and monophasic (MSS) subtypes of synovial
      sarcoma (SS) as well as the relationship between cells of solid/glandular areas
      and the spindle cells of BSS remain controversial. In order to further evaluate
      the immunohistochemical phenotype of SS we studied 34 primary tumours (15 BSS; 19
      MSS), 7 recurrences (4 from primary BSS; 3 from primary MSS) and 8 metastases (7
      BSS; one MSS), using several antibodies (EMA, CEA, keratins 1, 4, 5/6, 7, 8, 13,
      18, 19, 20, vimentin, collagen IV and laminin) that work in paraffin-embedded
      material. Spindle cells outside solid/glandular areas of BSS and in MSS showed
      immunoreactivity for keratins 5/6, 7, 8, 18 and 19. The transition of
      solid/glandular areas to surrounding spindle cells also showed keratin staining
      and failed to show a distinct separation regarding the immunoreactivity for
      laminin and collagen IV. Peripheral cells of solid/glandular areas were
      immunoreactive for vimentin. No major differences were observed between
      immunophenotypical cell profiles of BSS and MSS, apart from the exclusive
      immunostaining of solid/glandular areas of BSS for keratin 13 and CEA.
      Downgrading of keratin and extracellular matrix antigens immunoreactivity was
      observed when primary tumours were compared to recurrent and/or metastatic
      tumours of both subtypes (MSS and BSS). We conclude that SS should be regarded as
      carcinomas of soft tissues with an immunohistochemical phenotype depending on the
      degree of epithelial differentiation: spindle cells (MSS and BSS) predominantly
      expressing simple keratins, and poorly differentiated (solid/glandular) as well
      as well-differentiated (glandular) areas (BSS) expressing, in addition, complex
      epithelial-type keratins.

PMID- 7520166
TI  - Establishment and characterization of a malignant melanoma cell line (YP-MEL)
      derived from a patient with neurocutaneous melanosis.
AB  - A cell line, YP-MEL, was established from an intracranial malignant melanoma
      occurring in a neurocutaneous melanosis (NCMsis) patient. The established cell
      line was successfully cultured in serum-free medium with a doubling time of 41 h.
      The cells were refractile and small in size, with occasional pigmented giant
      cells. Histochemical and immunohistochemical features were compatible with common
      malignant melanoma and its cell line. Chromosome analysis revealed many
      supernumerary chromosomes and marker chromosomes including double minutes (DMs).
      When transplanted into nude mice, YP-MEL formed tumors histologically consistent
      with the original tumor. Addition of sera to the medium caused cellular spreading
      and elongation of cytoplasmic processes with an increase of melanin contents and
      tyrosinase activity. Because there was no melanoma cell line derived from a
      NCMsis patient, YP-MEL might be a beneficial tool for study on NCMsis.

PMID- 7520167
TI  - Effect of (+/-)-verapamil and hydralazine on stress- and chemically-induced
      gastric ulcers in rats.
AB  - The influence of (+/-)-verapamil and hydralazine on stress- and various
      chemically-induced gastric ulcers in rats together with their influence on
      various biochemical parameters which affect the development of the induced ulcers
      was examined. Pretreatment of rats with (+/-)-verapamil (4-16 mg kg-1 orally)
      significantly decreased cold-stress-induced gastric ulcers and enhanced ethanol
      induced ulcers. It did not affect indomethacin- (30 mg kg-1 orally) or reserpine-
      (5 mg kg-1 i.p.) induced ulcers. Pretreatment of the animals with hydralazine (1
      10 mg kg-1 orally) significantly enhanced ethanol-, reserpine- and cold-stress
      induced ulcers. It did not affect indomethacin-induced ulcers. Pretreatment of
      the animals with verapamil increased gastric mucus secretion, inhibited gastric
      acid secretion, decreased glutathione content and enhanced gastric lipid
      peroxidation whereas pretreatment of the animals with hydralazine significantly
      decreased gastric mucus secretion. Hydralazine did not affect gastric acid
      secretion, glutathione or gastric lipid peroxidation. The results of this study
      suggest that verapamil-induced protection against stress-induced ulcer may be due
      to its ability to suppress gastric acid secretion and to increase gastric mucus
      secretion. Its enhancement of ethanol-induced ulcers may be due to its ability to
      increase lipid peroxidation. The hydralazine-induced enhancement of the
      experimentally-induced ulcers may be due to its ability to suppress gastric mucus
      secretion.

PMID- 7520168
TI  - [Antigens of the HLA system in nodular formations of the thyroid gland].
AB  - Distribution of the HLA system Class 1 specificities was studied in 97 patients
      with thyroid carcinoma, 101 ones with nodular goiter and 500 donors in the
      Central Urals. B15, B18 antigens were very frequent and All antigens quite rare
      in the patients with thyroid carcinoma; in patients with nodular goiter the
      incidence of Aw19, A28, B18 antigens was the highest, whereas the incidence of
      A11 antigen and the A2-B35 haplotype was low. The groups of patients with thyroid
      carcinoma and nodular goiter differed only by the incidence of A28 antigen and A2
      B35 haplotype, this fact indicating the immunogenetic similarity of the diseases
      in question. Similar pathogenetic mechanisms of the formation of mammary
      carcinoma and of nodular goiter in the thyroid may be supposed, this giving
      grounds for the radical approach to the treatment of nodular formations of the
      thyroid.

PMID- 7520169
TI  - High-molecular-weight cytokeratin and cytokeratin-19 in the diagnosis of thyroid
      tumors.
AB  - The pathologic diagnosis of thyroid tumors is often difficult and subjective.
      Immunohistochemical markers including high molecular weight cytokeratin (HMW-CK),
      cytokeratin-19 (CK-19) and epithelial membrane antigen have been suggested to be
      helpful in the distinction of various types of thyroid neoplasia. We collected
      frozen and/or paraffin-embedded tissues from a total of 116 surgically resected
      thyroids including 31 nodular hyperplasias, 18 follicular adenomas, 48 papillary
      carcinomas and 19 follicular carcinomas, stained them for HMW-CK, CK-19 and
      epithelial membrane antigen, and graded the results on a scale from 0 to 3+.
      Although little staining for HMW-CK was seen in paraffin-embedded tissues,
      different results were obtained when both HMW-CK and CK-19 were tested on frozen
      tissues. In papillary carcinomas, including the follicular variant of papillary
      carcinoma, diffuse positivity for these antigens was seen immunohistochemically,
      and these antigens significantly distinguished papillary carcinomas from
      follicular neoplasms and nodular hyperplasias. Focal staining for epithelial
      membrane antigen was found in all pathological processes; thus this marker was
      not useful. We conclude that HMW-CK and CK-19 are useful in the distinction of
      papillary carcinomas from follicular adenomas, follicular carcinomas, and nodular
      hyperplasias when applied to frozen tissues. We recommend that samples of thyroid
      follicular nodules be frozen, and retrieved if necessary to aid in the
      differential diagnosis of these tumors.

PMID- 7520170
TI  - Cytokeratin in anaplastic large cell lymphoma.
AB  - A B-cell anaplastic large cell lymphoma, confirmed by immunohistochemistry and
      Southern blot immunoglobulin gene rearrangement analysis, contained neoplastic
      cells that were immunoreactive for cytokeratin using antibodies CAM 5.2, M20, MAK
      6, and KS-B17.2. Bands corresponding to cytokeratin 18 and cytokeratins 18 and 8
      were seen on Western blot immunoanalysis using antibodies KS-B17.2 and CAM 5.2.
      The lymph node also contained cytokeratin-positive extrafollicular fibroblastic
      reticulum cells. Although it is possible that the presence of cytokeratin in the
      cells of anaplastic large cell lymphoma represented phagocytosed filaments from
      the reticulum cells, it is more likely that the cytokeratins were synthesized by
      the malignant cells. The finding of cytokeratin in anaplastic large cell
      lymphoma, although infrequent, adds to the confusion in the diagnosis of this
      pleomorphic neoplasm.

PMID- 7520172
TI  - Mode of action of anti-lipopolysaccharide-binding protein antibodies for
      prevention of endotoxemic shock in mice.
AB  - Lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the
      response of monocytes to LPS in vitro. In a previous study, polyclonal anti-LBP
      IgGs were found to protect D-galactosamine-sensitized mice against a lethal
      endotoxemic shock induced by a low challenge of LPS or lipid A when administered
      simultaneously with endotoxin. In the present study, we investigated the mode of
      action of these anti-LBP IgGs. In vitro, we demonstrated that they interfere with
      LPS binding to monocytes or polymorphonuclear cells in different ways: by the
      mere prevention of binding of LPS to LBP thus preventing the binding of LPS to
      CD14, or by reacting with LPS-LBP complexes thus mediating their binding to
      complement or Fc receptors on monocytes and on polymorphonuclear cells. In vivo,
      we demonstrated that anti-LBP IgGs afforded protection against lethal endotoxemic
      shock by one of two mechanisms. First, LBP blockade by pretreatment with anti-LBP
      IgG allowed protection against a low dose of LPS (100 ng). This protection
      occurred despite LPS levels in blood similar to those in control mice but in the
      absence of detectable tumor necrosis factor (TNF). This demonstrated that anti
      LBP IgG could block the LBP-mediated TNF release upon LPS challenge. In contrast,
      anti-LBP IgG did not afford protection in mice not sensitized with D
      galactosamine and challenged with high-dose LPS (1 mg), confirming that LPS at
      high concentrations could stimulate cells independently of the LBP pathway.
      Second, anti-LBP treatment administered simultaneously with LPS challenge
      protected mice against both low and high doses of LPS. Unlike after pretreatment
      with anti-LBP IgG, this protection was accompanied by a decrease of circulating
      LPS, suggesting that anti-LBP IgG in these conditions facilitated clearance of
      LPS probably by clearing LPS-LBP complexes. These data and the fact that LBP
      binds to all LPS through lipid A suggest that antibody directed to LBP could be a
      candidate for therapeutic strategies in endotoxemic shock.

PMID- 7520171
TI  - Dephosphorylation of sperm midpiece antigens initiates aster formation in rabbit
      oocytes.
AB  - During fertilization in most mammals, the penetrating sperm organizes an aster of
      microtubules. We have investigated the mechanisms underlying this function of the
      sperm by a series of experiments based on microinjection of isolated sperm
      midpieces into unfertilized oocytes. These midpieces contain antigens recognized
      by the MPM-2 antibody. These antigens, which are absent from the rest of the tail
      fraction, correspond to three phosphorylated polypeptides of 77, 81, and 85 kDa.
      Dephosphorylation with alkaline phosphatase abolishes antigenicity on blots and
      in whole sperm. Reactivity to the antibody disappears between 1 and 3 hr after
      calcium stimulation of oocytes, following the decline in H1 kinase activity and
      coincident with aster formation. In unactivated oocytes, no aster forms and the
      antigen remains unchanged. MPM-2 treatment of midpieces prior to injection blocks
      their ability to form asters in oocytes activated by calcium stimulation. The
      epitope also disappears in 6-methyl-aminopurine-treated oocytes, implying that
      maintenance of the phosphorylated state requires kinase activity. A result that
      confirms this view is that sperm midpieces dephosphorylated by alkaline
      phosphatase can be rephosphorylated after injection into oocytes or by exposure
      in vitro to a Xenopus oocyte cytoplasmic fraction high in H1 kinase activity. We
      suggest that the microtubule nucleation activity of sperm midpieces after
      fertilization is triggered by the calcium-induced decrease in maturation
      promoting factor, which results in dephosphorylation of specific sperm
      centrosomal proteins.

PMID- 7520174
TI  - Impulse flow dependency of galanin release in vivo in the rat ventral
      hippocampus.
AB  - Using microdialysis and a sensitive RIA, we have studied the in vivo release of
      the neuropeptide galanin (GAL) from the ventral hippocampus of freely moving
      rats. The spontaneous outflow of GAL-like immunoreactivity (GAL-LI) (1.8 +/- 0.3
      fmol per ml per 20 min) was dependent on the presence of extracellular Ca2+ and
      was inhibited by tetrodotoxin. Evoked release induced by infusion of KCl (60 mM)
      or veratridine (148 microM) was also Ca(2+)-dependent and sensitive to
      tetrodotoxin. Electrical stimulation of the ventral limb of the diagonal band
      nuclei induced a frequency-dependent (50-200 Hz) and tetrodotoxin-sensitive
      overflow of GAL-LI in the hippocampus. In vitro GAL-LI release (1.0 +/- 0.02 fmol
      per ml per 5 min), studied in slices of rat ventral hippocampus, was also Ca(2+)
      dependent and was increased in a concentration-dependent manner by KCl
      depolarization. This study demonstrates the release of the neuropeptide GAL in
      the rat central nervous system. The in vivo release is related to the activity of
      the cholinergic GAL-LI-containing cells in the septal diagonal band nuclei. The
      results are discussed in relation to the coexistence of GAL and acetylcholine
      within the septal/diagonal band complex.

PMID- 7520173
TI  - Inhibition of hematopoiesis by competitive binding of transcription factor PU.1.
AB  - Transcription factors have been shown to play a role as "master switch" factors
      in the programming of hematopoietic cell commitment and differentiation. PU.1 is
      a hematopoietic-specific member of the Ets family of transcription factors. In
      human bone marrow CD34-enriched progenitor cells, PU.1 expression was upregulated
      during the early phases of granulocytic/monocytic differentiation, preceding
      expression of its target genes encoding CD11b and the macrophage-colony
      stimulating factor receptor, whereas PU.1 was expressed at stable levels
      throughout erythroid differentiation. To study PU.1 function, we synthesized
      double-stranded phosphorothioate oligonucleotides containing a characterized PU.1
      site and demonstrated their ability to specifically compete for PU.1 DNA binding.
      When added to CD34+ cells in vitro, wild-type PU.1-binding oligonucleotides
      significantly blocked hematopoietic colony formation, whereas mutated PU.1
      oligonucleotides which no longer bind PU.1 had no specific inhibitory effect.
      These results demonstrate that PU.1 is developmentally upregulated during normal
      human myelopoiesis and that the function of PU.1 is critical for the development
      of in vitro hematopoiesis.

PMID- 7520178
TI  - Dopamine alters glutamate receptor desensitization in retinal horizontal cells of
      the perch (Perca fluviatilis).
AB  - The patch-clamp technique in combination with a fast liquid filament application
      system was used to study the effect of dopamine on the glutamate receptor
      desensitization in horizontal cells of the perch (Perca fluviatilis). Kinetics of
      ligand-gated ion channels in fish horizontal cells are modulated by dopamine.
      This modulation is presumably mediated by a cAMP-dependent protein
      phosphorylation. Before incubation with dopamine, the glutamate receptors of
      horizontal cells activate and desensitize with fast time constants. In the whole
      cell recording mode, fast application of the agonists L-glutamate, quisqualate,
      or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid prior to the dopamine
      incubation gives rise to fast transient currents with peak values of about 200 pA
      that desensitize within 100 ms. Kainate as agonist produced higher steady-state
      currents but no transient currents. After incubation of the cells with dopamine
      for 3 min, the desensitization was significantly reduced and the agonists L
      glutamate, quisqualate, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid induced steady-state currents with amplitudes that were similar to the
      previously observed transient currents. Kainate-induced currents were only
      slightly affected. Fast desensitizing currents upon fast application of L
      glutamate were also recorded from outside-out patches that were excised from
      horizontal cells before incubation with dopamine. The currents from excised
      patches desensitized to a steady-state level of about 0.2 of the peak amplitude
      with time constants of less than 2 ms. When the outside-out patches were excised
      from cells after dopamine incubation, steady-state currents were enhanced and no
      transient currents were observed. The results may indicate that the dopamine
      dependent modulation of glutamate-induced currents, which is presumably mediated
      by a protein phosphorylation, is due to an alteration of the desensitization of
      the glutamate receptors.

PMID- 7520180
TI  - Structure and function of channel-forming peptaibols.

PMID- 7520175
TI  - A purified selenophosphate-dependent enzyme from Salmonella typhimurium catalyzes
      the replacement of sulfur in 2-thiouridine residues in tRNAs with selenium.
AB  - A tRNA-modifying enzyme tentatively termed tRNA 2-selenouridine synthase was
      purified by a five-step procedure that resulted in 50-60% pure preparations. This
      enzyme catalyzes the conversion of a 5-methylaminomethyl-2-thiouridine residue in
      the tRNA substrate to 5-methylaminomethyl-2-selenouridine. The selenium donor
      substrate for this reaction is shown to be selenophosphate which is formed from
      ATP and selenide by selenophosphate synthetase. Replacement of sulfur with
      selenium in tRNAs catalyzed by tRNA 2-selenouridine synthase occurs in the
      absence of ATP. The dependence of reaction velocity on selenophosphate
      concentration obeys Michaelis-Menten kinetics indicating an apparent Km value of
      17.1 microM. Bulk thio-tRNA preparations from Escherichia coli and Salmonella
      typhimurium are equally effective as substrates for the selenium incorporation
      reaction. An intact 3' end of the tRNA molecule does not seem to be essential for
      selenium incorporation. Identity of the product of the reaction was confirmed by
      HPLC analysis of digests of [75Se]seleno-tRNAs labeled by incubation with the
      purified enzyme. A labeled compound in the nucleoside mixture was coeluted with
      authentic 5-methylaminomethyl-2-selenouridine.

PMID- 7520177
TI  - The expression of serine carboxypeptidases during maturation and germination of
      the barley grain.
AB  - cDNA clones encoding three additional serine carboxypeptidases (Ser-CPs) have
      been isolated from a gibberellic acid-induced barley aleurone cDNA library. The
      three deduced Ser-CPs belong to the two-chain subfamily of Ser-CPs; they are
      synthesized as precursors with a putative signal peptide, propeptide, and linker
      peptide between the A and B chains. Their identification provides the proof for
      the existence of more than three Ser-CPs in cereal grains, and, based on their
      sequences, they may exhibit new substrate specificities. The expression of these
      and of the three previously isolated Ser-CPs from barley grains (CP-MI, CP-MII,
      and CP-MIII) has been investigated by Northern and Western analysis and RNA PCR.
      CP-MII is the only Ser-CP to be expressed and accumulate in the developing grain
      and is stored in its active form in the mature grain. All six Ser-CPs are
      expressed de novo in the germinating grain, in the scutellum, and/or in the
      aleurone. Furthermore, at least CP-MI, CP-MII, and CP-MIII are secreted into the
      endosperm. In addition, all Ser-CPs (except CP-MI) are also expressed in the
      roots and shoots of the growing seedling. This enzyme family thus appears to be
      ubiquitous in the barley plant, which suggests that Ser-CPs play additional roles
      besides their participation in the mobilization of storage proteins.

PMID- 7520179
TI  - Nitric oxide is required for tactile learning in Octopus vulgaris.
AB  - Nitric oxide, produced by nitric oxide synthase in brain tissue, is essential for
      several different kinds of learning in vertebrates. We present the first evidence
      that it is also essential for learning in an invertebrate. Intramuscular
      injections of an inhibitor of the enzyme completely block touch learning in
      Octopus vulgaris. Eight control animals learned a touch paradigm, but none of
      eight synthase-inhibited ones learned it.

PMID- 7520181
TI  - Malignant obstruction of the common bile duct: long-term results of Gianturco
      Rosch metal stents used as initial treatment.
AB  - PURPOSE: To determine how long Gianturco-Rosch metal stents remain patent when
      used as the initial treatment for malignant obstruction of the common bile duct.
      MATERIALS AND METHODS: The patency of Gianturco-Rosch metal stents was
      prospectively studied in 26 patients with malignant obstructive jaundice. Biliary
      obstruction was caused by pancreatic carcinoma (n = 15), cholangiocarcinoma (n =
      10), or metastatic lymphadenopathy (n = 1). Follow-up information was obtained
      every 3-4 months until death. RESULTS: Stent insertion was successful in all
      patients. Stent occlusion occurred in nine patients (35%). The overall mean
      patency period was 39.9 weeks. Adequate biliary drainage for a minimum of 80
      weeks or until death was achieved in 19 patients (73%). Life-table analysis
      predicted stent patency rates of 86%, 75%, and 69% at 12, 24, and 48 weeks,
      respectively. CONCLUSION: These results are better than those previously reported
      in patients with plastic endoprostheses. The authors believe that insertion of
      the metal stent is the procedure of choice in patients with inoperable malignant
      biliary obstruction.

PMID- 7520176
TI  - Specificity of the mutator caused by deletion of the yeast structural gene (APN1)
      for the major apurinic endonuclease.
AB  - The loss of bases from cellular DNA occurs via both spontaneous and mutagen
      induced reactions. The resulting apurinic/apyrimidinic (AP) sites are cytotoxic
      and mutagenic but are counteracted by repair initiated by AP endonucleases.
      Previously, in vitro and bacterial transfection studies suggested that AP sites
      often prompt insertion of dAMP residues during replication, the A-rule.
      Dissimilar results have been obtained by transfecting DNA into eukaryotic cells.
      It seemed possible that these differences might be due to idiosyncrasies of
      transfection or aberrant replication of the transecting DNA. The observation that
      AP endonuclease-deficient strains of the yeast Saccharomyces cerevisiae have
      elevated spontaneous mutation rates allowed us to determine the mutational
      specificity of endogenously generated AP sites in nuclear DNA. With the yeast
      SUP4-o gene as a mutational target, we found that a deficiency in the major yeast
      AP endonuclease, Apn1, provoked mainly single base-pair substitution; the rate of
      transposon Ty insertion was also enhanced. The rate of transversion to a G.C pair
      was increased 10-fold in Apn1-deficient yeast, including a 59-fold increase in
      the rate of A.T-->C.G events. In contrast, the rate of transversion to an A.T
      pair was increased by only 3-fold. A deficiency in N3-methyladenine glycosylase
      offset these substitution rate increases, indicating that they are due primarily
      to AP sites resulting from glycosylase action. Thus, the A-rule does not seem to
      apply to the mutagenic processing of endogenous abasic sites in S. cerevisiae.
      Other results presented here show that AP endonuclease-deficient Escherichia coli
      exhibit a mutator phenotype consistent with the A-rule.

PMID- 7520183
TI  - Isolated mild fetal cerebral ventriculomegaly: clinical course and outcome.
AB  - PURPOSE: To assess the outcome of fetuses with isolated mild ventriculomegaly
      (IMVM). MATERIALS AND METHODS: The clinical course of 44 fetuses with IMVM was
      investigated. Cognitive and motor development was classified as normal or
      delayed. RESULTS: Clinical data were available for 37 subjects. Three (8%)
      neonates died. Of the 34 living children, follow-up was limited (< 9 months) in
      six and the clinical course beyond the 1st year of life was established in 28.
      Twenty-two (79%) of the 28 children are developing normally, whereas six (21%)
      are developmentally delayed. More than 90% of fetuses with ventricular atrial
      diameter of 10-11 mm are normal. Seventy-five percent of fetuses with IMVM were
      male. With exclusion of the six children with limited follow-up, 78% of boys
      older than 1 year are developmentally normal compared with only 50% of girls.
      CONCLUSION: The majority of living children with prenatally detected IMVM are
      developmentally normal, especially those with borderline ventriculomegaly. Gender
      differences in prevalence and outcome deserve further investigation.

PMID- 7520184
TI  - Cure for double vision.

PMID- 7520182
TI  - Initial clinical experience with dextran-coated superparamagnetic iron oxide for
      detection of lymph node metastases in patients with head and neck cancer.
AB  - PURPOSE: To investigate the efficacy of magnetic resonance (MR) imaging with
      dextran-coated superparamagnetic iron oxide in the differentiation of metastatic
      and benign nodes in patients with head and neck cancer. MATERIALS AND METHODS: MR
      imaging was performed before and after intravenous administration of iron oxide
      in 12 patients. Ninety-one pathologically proved nodes were visually analyzed,
      and 66 lymph nodes were quantitatively analyzed by measuring signal intensity in
      visually selected regions of interest. RESULTS: Forty of 42 histologically proved
      metastatic nodes and 41 of 49 benign nodes were detected, yielding 95%
      sensitivity and 84% specificity. The signal intensity ratio of benign nodes was
      substantially lower than that of metastatic nodes, indicating better
      differentiation of metastatic and benign nodes. Furthermore, 13 of 14 normal
      sized nodes were detected. CONCLUSION: MR imaging with iron oxide can enable
      specific differentiation of metastatic and benign nodes in patients with head and
      neck cancer. This agent may potentially enhance the detection of metastatic lymph
      nodes and deserves further investigation.

PMID- 7520185
TI  - Modulation of inhibitory and excitatory amino acid receptor ion channels by zinc.

PMID- 7520186
TI  - Mechanisms mediating the effects of cholecystokinin on avian small intestine
      longitudinal smooth muscle.
AB  - The aims of this study were (1) to define the effects of CCK-8s and related
      peptides on chicken ileum longitudinal smooth muscle and (2) to explore the
      mechanisms by which such effects occur. The effects of CCK-8s were assayed in
      vitro on chicken longitudinal ileal strips. CCK-8s produced contraction of ileal
      strips (EC50 8.8.10(-9) M). CCK-8ns and CCK-4 did not have remarkable contractile
      effects even when added at concentrations 200-times higher than the EC50 for CCK
      8s. L365,260 slightly inhibited the effects of CCK-8s whereas L364,718 was
      ineffective. Tetrodotoxin (10(-6) M) markedly decreased the effects of CCK-8s.
      Atropine (10(-6) M) did not modify the neurally mediated effects of CCK-8s,
      whereas ketanserin (10(-5) M) decreased the response to CCK-8s. Substance P
      desensitized preparations exhibited reduced responses to CCK-8s. Our results
      indicate that CCK receptors present in chicken ileum behave similarly but not
      identically to the CCK-A receptor described in mammals. Most of these CCK
      receptors are neurally located but a minor proportion is also present on smooth
      muscle. The neurally mediated response to CCK-8s does not involve cholinergic
      mechanisms, but serotonin and substance P releasing neurons.

PMID- 7520187
TI  - [Constitutional syndrome and changes in the intestinal pattern].

PMID- 7520189
TI  - Prevalence of HPV in premalignant and malignant cervical lesions in Greenland and
      Denmark: PCR and in situ hybridization analysis on archival material.
AB  - Archival formalin-fixed paraffin-embedded cervical specimens from 125 women in
      Greenland and 139 women in Denmark who had CIN I-III or cervical cancer diagnosed
      between 1983 and 1987 were analysed for human papillomavirus type 16 (HPV-16) by
      in situ hybridization and for HPV-16, 18, 31, 33, 35 and 45 by PCR. In situ
      hybridization analysis showed an HPV-16 prevalence of 17% (16/95) and 23%
      (24/105) in the premalignant lesions from Greenland and Denmark, respectively.
      The HPV-16 prevalence rate in the cancer specimens was 10% (3/30) in the samples
      from Greenland and 29% (10/34) in the Danish specimens. A total of 82 Greenlandic
      and 107 Danish specimens were beta-globin-positive by PCR reaction. HPV-16
      specific PCR on these samples showed 63% (34/54) of the Greenlandic and 68%
      (50/74) of the Danish preinvasive lesions to be positive. The corresponding HPV
      16-positive rates for the invasive cancers were 82% (23/28) for Greenland and 70%
      (23/33) for Denmark. This study of patient samples supports our previous
      population-based studies in which similar HPV-detection rates were found among
      random samples of women from Greenland and Denmark, although Greenland has a 4-5
      fold higher cervical cancer incidence.

PMID- 7520188
TI  - [Effects of low doses of aprotinin in heart surgery].
AB  - OBJECTIVES: To study the effect of aprotinin (Trasylol) administration on
      bleeding after surgery and on the need for blood transfusion in patients
      undergoing cardiopulmonary bypass with extracorporeal circulation (ECC). PATIENTS
      AND METHODS: One hundred ten patients were studied prospectively, divided into
      two groups. In the aprotinin group (n = 80), the ECC pump was primed with 140 mg
      of aprotinin and followed with continuous intravenous perfusion at 70 mg/h from
      the start of ECC until the patient left the operating theater. The control group
      (n = 30) served as reference. The parameters compared were the hematocrit, number
      of platelets, prothrombin time and activated coagulation time, as well as
      drainage of blood through thoracic tubes at 3 and 24 h after surgery and the
      amount of blood transfused both during and after the procedure. RESULTS: Blood
      loss was significantly lower in the aprotinin group as compared with the control
      group, both at 3 h (227 +/- 193 vs 380 +/- 169 ml; p < 0.05) and at 24 h (422 +/-
      322 ml vs 736 +/- 342 ml; p < 0.05) after surgery. There was also a significant
      decrease in blood requirements in the aprotinin group (550 +/- 450 ml vs 872 +/-
      747 ml; p < 0.05). There were no differences between the two groups for the other
      parameters studied. CONCLUSIONS: Administration of aprotinin at low doses during
      surgery in patients undergoing cardiac surgery with ECC significantly reduces
      postoperative bleeding and the amount of blood transfused.

PMID- 7520191
TI  - Tachykinin antagonists in carotid body responses to hypoxia and substance P in
      the rat.
AB  - In the present study, we tested the hypothesis that substance P (SP) is an
      excitatory peptide to the rat carotid body and plays an important role in
      chemosensory excitation by hypoxia. Chemosensory discharge was recorded from the
      cut carotid sinus nerve in 19 anaesthetized, paralyzed and mechanically
      ventilated rats. Intracarotid administration of SP augmented the chemoreceptor
      activity in a dose-dependent manner. Maximal excitation was seen with 10 nmol SP.
      Carotid body stimulation by SP was independent of its effects on arterial blood
      pressure. The effect of SP antagonists, D-Pro2-D-Trp7,9-SP (DPDT-SP) or Spantide,
      on chemoreceptor responses to SP and hypoxia was examined in 12 rats. Close
      carotid body administration of either antagonist at doses of 40 micrograms.kg
      1.min-1 elicited an augmentation followed by a progressive depression of baseline
      carotid body activity. SP antagonists significantly reduced peptide-induced
      carotid body stimulation and also markedly attenuated the chemoreceptor response
      to hypoxia. Systemic administration of sodium bicarbonate stimulated the carotid
      bodies, presumably by releasing CO2, and the bicarbonate-induced chemoreceptor
      stimulation was not affected by SP antagonists. From these results we conclude
      that in rats (a) SP stimulates the carotid bodies independently of its effects on
      arterial blood pressure, and (b) SP is associated with the chemosensory
      stimulation by hypoxia but not with other excitatory stimuli.

PMID- 7520190
TI  - Identification of mosquito-borne flavivirus sequences using universal primers and
      reverse transcription/polymerase chain reaction.
AB  - A reverse transcription/polymerase chain reaction (RT/PCR) protocol for the rapid
      detection and identification of flaviviruses was developed using a set of
      universal oligonucleotide primers. These primers correspond to sequences in the
      3' non-coding region and in the NS5 gene which are highly conserved among the
      mosquito-borne flaviviruses. The sequences of the resulting amplified products
      were analysed for dengue 1, dengue 2, dengue 3, dengue 4, Japanese encephalitis,
      West Nile, yellow fever and Zika viruses, and compared with the published
      sequences of other flaviviruses. The 291-297 nucleotides corresponding to the C
      terminus of NS5 gene showed 56 to 76% similarity, whereas the 3' non-coding
      region (190 to 421 nucleotides) showed only 20 to 36% similarity. Genetic
      classification of the Zika virus supported its traditional serological grouping.
      Recombinant plasmids containing the flavivirus sequences were used in a nucleic
      acid hybridization test to identify the RT/PCR products derived from viral RNA
      extracted from experimentally infected mosquitoes. The plasmids were dotted on a
      strip of nitrocellulose membrane and incubated with the RT/PCR product labelled
      with digoxigenin during the PCR step. This is a valuable method for the rapid and
      specific identification of mosquito-borne flaviviruses in biological specimens
      and for subsequent sequence analysis.

PMID- 7520192
TI  - [Chediak-Higashi-like inclusions in acute myeloblastic leukemia. Ultrastructural
      study].
AB  - The pseudo-Chediak-Higashi anomaly is characterized by the presence of giant
      granules in the cytoplasm of blast cells in acute leukemia. We report here a new
      case of acute myelogenous leukemia (M2 type) with this alteration. The granules
      were azurophilic or eosinophilic and reacted strongly to peroxidase stain.
      Ultrastructural studies showed that the granules contained a dense matrix and
      occasionally "finger print" structures at the periphery; in some inclusions,
      fibrillar structures of myelinic figures could be seen. The matrix was reactive
      to peroxidase and small vesicles were prominent in the cytoplasm near the
      granules. We conclude that the giant granules could have been formed by the
      fusion of primary granules and/or by the fusion of these small dense vesicles.

PMID- 7520194
TI  - [Agranulocytosis induced by drugs. Rapid recovery with the early use of G-CSF].

PMID- 7520193
TI  - [Partial deletion of the D antigen in a family group. Determination of its
      antigenic density by flow cytometry].
AB  - Mutations within the genetic Rh system can produce partial deletions of one or
      more epitope of the D antigen, known as incomplete D. These people, classified Rh
      positive, are capable of producing anti-D antibodies when exposed to D positive
      red blood cells (rbcs). We describe the study of a Rh positive, 34 year old,
      spanish-indian ("mestiza") female patient, in whose blood anti-D antibodies were
      detected after a blood transfusions. The results of the tests showed a partial
      deletion of the D antigen in the patient and three of her family members.
      PATIENTS AND METHODS: The following tests were done to the patient and her family
      members: 1) ABO and Rh typing; 2) Direct antiglobulin test; 3) Detection of
      irregular antibodies in their blood serum; 4) Rh genotype; 5) Cross matching of
      the patient's serum with rbcs of her Rh positive relatives; 6) Titration of a
      monoclonal anti-D (IgM) and a polyclonal anti-D (IgG) of human origin with the
      patient's rbcs and with Rh positive rbcs of her family members whose erythrocytes
      didn't react with the patient's serum; 7) Measurement of the antigenic density of
      the D antigen by flow cytometry (indirect immunofluorescence) in the rbcs of the
      patient and in those family members who had the defect, using a polyclonal anti-D
      (IgG). RESULTS: 1) An anti-D antibody which didn't react with its own Rh positive
      rbcs was found in the patient's serum; 2) This antibody didn't react with the Rh
      positive rbcs of her father and two out of her 4 brothers; 3) The cytometric
      study of these cells (R)r) showed a immunofluorescence pattern weaker than the
      control cells of the same genotype, but with a variable expression between 15 to
      41%. CONCLUSIONS: The study showed: 1) The presence of an anti-D antibody in a Rh
      positive patient who had been previously sensitized (by blood transfusion); 2)
      This antibody was able to react with Rh positive rbcs but not with those of the
      patient and her family members who had the same partial deletion; 3) The defect
      was transmitted heterozygously, with a high degree of penetration, but with
      variable expression; 4) A low antigenic density for her D antigen by flow
      cytometry.

PMID- 7520195
TI  - [Utilization of colony-stimulating factors in severe aplastic anemia].

PMID- 7520196
TI  - Why do things look as they do?

PMID- 7520197
TI  - Old dyes for new scopes: the phagocytosis-dependent long-term fluorescence
      labelling of microglial cells in vivo.
AB  - The nature of the interactions between dying neurons and microglial cells within
      the developing and injured CNS remains controversial. A new technique for
      labelling microglial cells is available, which enables further studies of such
      interactions in a direct way. The value of the method relies on retrograde
      filling of neurons with vital fluorescent dye, subsequent degeneration of the
      neurons due to either naturally occurring cell death or as the result of axotomy,
      and phagocytotic removal of the fluorescent cell debris by microglial cells,
      which thus become identifiable. The fluorescent dye can be visualized in whole
      mounted tissue or after sectioning. Photoconversion of the dye into electron
      dense material permits examination of the microglial and dying ganglion-cell
      interactions at the ultrastructural level. This new principle of the function
      dependent, selective fluorescent labelling of phagocytosing microglial cells,
      which might now be extended to other dyes and to other neurodegenerative models,
      promises to shed light onto the function of microglial cells within the brain.

PMID- 7520198
TI  - Neurotrophic factors: from molecule to man.
AB  - Recent advances in the understanding of the physiological role of nerve growth
      factor (NGF) have raised the question of whether neurotrophic factors might have
      clinical potential in the treatment of neurodegenerative disease or nerve trauma.
      Although NGF was first characterized as a target-derived survival factor for
      developing sympathetic and sensory neurons, it is now clear that it plays an
      important role in the maintenance and regeneration of mature peripheral neurons.
      However, the highly restricted specificity of NGF for sympathetic neurons,
      subpopulations of neural-crest-derived sensory neurons, and striatal and basal
      forebrain cholinergic neurons has, for almost two decades, stimulated the search
      for other neurotrophic factors that might act on the many classes of neurons that
      do not respond to NGF. In this article, the biology of the recently discovered
      NGF-related family of neurotrophic factors and ciliary neurotrophic factor and
      their receptors are reviewed, especially in the context of the therapeutic
      potential of these factors in the treatment of neurological disorders of the CNS.

PMID- 7520199
TI  - Santiago Ramon y Cajal and the Croonian Lecture, March 1894.

PMID- 7520200
TI  - Free radicals and neurodegeneration.

PMID- 7520201
TI  - Intrinsic programmes of growth and survival in developing vertebrate neurons.
AB  - Neurons become dependent on a supply of target-derived neurotrophins for survival
      when their axons reach their targets in development. Because the distance axons
      have to grow varies from one population of neurons to another, the timing of
      dependence on neurotrophins likewise varies. Although it would be expected that
      the simplest way of getting the timing right would be for the target to provide a
      suitable signal to the arriving axons, detailed studies on developing cranial
      sensory neurons suggest that these neurons are programmed, before
      differentiation, to acquire dependence at the correct time independently of
      external signals. Neurons not only partly compensate for different target
      distances by extending axons more rapidly the further they have to grow, but
      possess an intrinsic clock that switches on dependence at the right time in
      accordance with the time it normally takes their axons to reach their targets.
      Here the experimental evidence for these intrinsic programmes of growth and
      survival is reviewed, the rationale that might have favoured their evolution is
      discussed, and parallels are drawn with other developing neuronal systems.

PMID- 7520202
TI  - Synchronized sleep oscillations and their paroxysmal developments.
AB  - The state of resting sleep is associated with a series of oscillations generated
      in cortical and thalamic networks. A newly discovered rhythm groups the spindle
      and delta sleep oscillations within slowly recurring (< 1 Hz) sequences. Multi
      site, extra- and intracellular recordings provide evidence for synchronization of
      various classes of cell in the neocortex and thalamus during sleep oscillations
      that might reach paroxysmal levels similar to epileptic states. Sleep
      oscillations and the underlying synchronizing processes are disrupted during
      transition to brain arousal.

PMID- 7520203
TI  - Neurotransmission in the rat amygdala related to fear and anxiety.
AB  - An impressive amount of evidence from many different laboratories using a variety
      of experimental techniques indicates that the amygdala plays a crucial role in
      the acquisition, consolidation and retention or expression of conditioned fear.
      Electrophysiological data are beginning to detail the transmitters and inter
      amygdala connections that transmit information to, within, and out of the
      amygdala. In general, treatments that increase the excitability of amygdala
      output neurons in the basolateral nucleus (for example, by decreasing opiate and
      GABA transmission, and increasing noradrenergic transmission) improve aversive
      conditioning, whereas treatments that decrease excitability of these neurons (by
      increasing opiate and GABA transmission, and decreasing NMDA and noradrenergic
      transmission) retard aversive conditioning as well as producing anxiolytic
      effects in appropriate animal tests. A better understanding of brain systems that
      inhibit the amygdala, as well as the role of its very high levels of peptides,
      might eventually lead to the development of more effective pharmacological
      strategies for treating clinical anxiety and memory disorders.

PMID- 7520204
TI  - [The determination of optimal regimens for producing Klebsiella antigenic
      erythrocytic immunoreagents].
AB  - The optimum conditions for obtaining sensitive K- and D-serovar-specific
      Klebsiella antigenic erythrocyte diagnosticum have been established. The methods
      of choice are sensitization with lipopolysaccharide antigens at pH 5.0 and in a
      neutral medium at a temperature of 45 degrees C for an hour. The reagents thus
      obtained have proved to be specific when tested in the passive hemagglutination
      test with antisera to Shigella, Salmonella and Escherichia.

PMID- 7520205
TI  - [Staphylococcus aureus-induced antigen-specific immunosuppression].
AB  - In experiments made on noninbred white mice the manifestations of delayed
      hypersensitivity and the number of antibody-producing cells in regional lymph
      nodes or the spleen were determined on day 5 after the subcutaneous or
      intraperitoneal immunization of the animals with sheep red blood cells (SRBC). At
      the same time the injection of S. aureus antigens simultaneously with SRBC raises
      the threshold of antigenic sensitivity and decreases the manifestations of cell
      mediated and humoral immune response to SRBC. This suppressive effect was even
      more pronounced in the local immune process and was partially mediated by the
      hyperproduction of prostaglandins.

PMID- 7520206
TI  - The inflammatory lesion of T cell line transferred experimental autoimmune
      encephalomyelitis of the Lewis rat: distinct nature of parenchymal and
      perivascular infiltrates.
AB  - We have investigated the T cell receptor (TCR) repertoire in the inflammatory
      infiltrates of T line-transferred experimental autoimmune encephalomyelitis (EAE)
      of the Lewis rats. Using a panel of TCR V beta-specific monoclonal antibodies
      (mAbs) and immunocytochemistry, we studied the nature of the T cells entering the
      central nervous system (CNS) after transfer of either myelin basic protein (MBP)
      reactive, or MBP-reactive but non-encephalitogenic T cell lines. All the MBP
      specific T cell lines predominantly used the V beta 8.2 TCR chain. T cell lines
      specific for the tuberculin purified protein derivative (PPD), using TCR V genes
      different from V beta 8.2, served as controls. We first studied the time course
      of T cells entering the CNS. In all recipient rats, small, but significant
      numbers of alpha beta-TCR-expressing infiltrate cells appeared in the CNS within
      the first 24 h after T cell transfer. In animals injected with either type of MBP
      reactive T cells, the early infiltrate cells were preferentially located within
      the parenchyma of the spinal cord, while in PDD T line-injected rats, the
      lymphocytes were mostly found in the meninges. TCR V beta gene usage was examined
      on the peak of clinical disease. Six days after T cell transfer, the TCR
      repertoire used by infiltrating lymphocytes in general seemed to be highly
      diverse. None of the V beta isotypes examined (i.e. V beta 8.2, V beta 8.5 or V
      beta 10) was used by a major population of the alpha beta-TCR-positive T
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520208
TI  - The interferons--Part 2.

PMID- 7520207
TI  - [Histamine liberation and specific IgE against Dermatophagoides pteronyssinus in
      parasitized patients].
AB  - We studied 98 patients with different parasitosis, without clinical symptoms of
      mite sensitization, most of them coming from Guinea. Histamine release to
      Dermatophagoides pteronyssinus was performed using whole blood. Specific IgE to
      the same antigen was measured by EAST, as well as by an immunodot with the same
      antigen extract employed for the histamine release test. Finally, the EAST
      positive sera were studied by immunoblotting. The presence of specific IgE by
      EAST could be proved in 31 patients, but these antibodies were nor detected by
      dot, blot and histamine release. On the other hand, only two patients showed a
      positive histamine release test to D. pteronyssinus and in these two cases the
      EAST to mites was negative. There was no relation between total IgE levels and
      specific IgE to mites. The presence of mite-specific IgE showed a significative
      association to the parasite Trichuris trichiura (odds ratio 3.09). This fact
      suggest that the specific IgE values found in this population can reflect some
      cross-reaction between parasites and allergens. It is the author's opinion that
      the same study should be performed in european patients in order to test the
      relationship between mite-specific antibodies and the presence of parasites,
      specially of Trichuris trichiura.

PMID- 7520209
TI  - Importance of ST-segment depression as a determinant of ventricular premature
      complex frequency after thrombolysis for acute myocardial infarction. Tissue
      Plasminogen Activator: Toronto (TPAT) Study Group.
AB  - Ventricular premature complexes (VPCs) after acute myocardial infarction (AMI)
      remain important determinants of survival in the post-thrombolytic era. The role
      of thrombolysis, left ventricular function, and Holter ST-segment depression in
      modulating VPC frequency is unclear. In a placebo-controlled, randomized study of
      tissue-type plasminogen activator (t-PA) in 103 patients with AMI (Tissue
      Plasminogen Activator: Toronto study), VPC frequency and ST depression on Holter
      monitoring (day 7), ejection fraction by radionuclide scan (day 9), and infarct
      artery patency and cross-sectional area on day 1 (n = 42) were assessed. After
      administering t-PA, VPC frequency was 10 +/- 58/hour (mean +/- SD), similar to
      that after placebo (23.5 +/- 91.7, p = NS). However, patients with ST depression
      had greater VPC frequency (56 +/- 140/hour) than those without it (1.3 +/-
      2.6/hour, p = 0.05). Ejection fraction was negatively correlated with VPC
      frequency (r = -0.33, p < 0.001). By multivariate analysis, ejection fraction (F
      = 7.0, p < 0.01) and ST depression (F = 5.8, p < 0.02) were the only independent
      predictors of VPC frequency. In this placebo-controlled study, VPC frequency
      after AMI was not related to thrombolytic administration but was associated with
      ST depression and ejection fraction. This suggests that the underlying extent of
      both infarcted and ischemic myocardium is important in modulating ventricular
      arrhythmias after AMI.

PMID- 7520210
TI  - The effect of chlorthalidone on ventricular ectopic activity in patients with
      isolated systolic hypertension. The SHEP Study Group.
AB  - In an ancillary study of the Systolic Hypertension in the Elderly Program (SHEP),
      the effects of diuretics on ventricular ectopic activity were investigated in 186
      patients with isolated systolic hypertension. Ventricular premature complexes
      (VPCs) were examined as the number of VPCs/24 hours, presence of > or = 1 VPC,
      presence of > or = 10 VPCs/24 hours, and presence of VPC pairs or ventricular
      tachycardia. Significant changes in VPCs were not observed either in the 92
      patients randomized to chlorthalidone stepped-care (12.5 and 25 mg/day) or in the
      94 placebo-treated patients (p > 0.1 for all VPC definitions and both groups).
      Serum potassium decreased from 4.4 +/- 0.5 to 4.1 +/- 0.5 mEq/liter (p = 0.002)
      in the chlorthalidone group and did not change (4.4 +/- 0.5 to 4.5 +/- 0.4
      mEq/liter) in the placebo group. Potassium was prescribed routinely for confirmed
      hypokalemia < 3.5 mEq/liter. A relation between serum potassium and VPC or change
      in serum potassium and change in VPC was not observed in the chlorthalidone
      group. In summary, in patients with isolated systolic hypertension,
      chlorthalidone in doses that are effective in decreasing stroke and
      cardiovascular event rates (12.5 or 25 mg/day), did not increase VPCs.

PMID- 7520211
TI  - The effect of fetomaternal bleeding on the risk of adverse pregnancy outcome in
      patients with elevated second-trimester maternal serum alpha-fetoprotein levels.
AB  - OBJECTIVE: Unexplained maternal serum alpha-fetoprotein elevation has been
      associated with an increased risk of intrauterine growth retardation, preterm
      delivery, and intrauterine fetal death. The purpose of this study was to
      determine whether patients with evidence of recent fetomaternal bleeding as a
      cause of elevated maternal serum alpha-fetoprotein level are at a lower risk for
      adverse pregnancy outcome than those without such evidence. STUDY DESIGN:
      Patients with elevated maternal serum alpha-fetoprotein levels who had a
      singleton viable fetus without ultrasonographically detectable anomalies were
      offered inclusion in this study. Study participants had blood drawn for fetal
      cell analysis before amniocentesis. The pregnancy outcomes of patients with
      evidence of fetomaternal bleeding were compared with those of patients without.
      RESULTS: Of 229 patients, 109 (47.6%) had evidence of fetomaternal bleeding as a
      possible cause of elevated maternal serum alpha-fetoprotein. Of these, 86 (78.9%)
      had a normal pregnancy outcome compared with 84 of 120 (70.0%) with a negative
      stain for fetal cells (p not significant). There was no significant difference in
      the incidence of preterm delivery (14 [12.8%] vs 15 [12.5%]), intrauterine growth
      retardation (5 [4.6%] vs 9 [7.5%]), or intrauterine fetal death (4 [3.7%] vs 8
      [6.6%]) when patients with a positive stain for fetal cells were compared with
      those with a negative stain. CONCLUSION: Among patients with elevated maternal
      serum alpha-fetoprotein levels, those with evidence of recent fetomaternal
      bleeding do not appear to be at decreased risk for adverse pregnancy outcome
      compared with those without such evidence.

PMID- 7520212
TI  - The prognostic value of serum progesterone and quantitative beta-human chorionic
      gonadotropin in early human pregnancy.
AB  - OBJECTIVE: Our purpose was to determine whether serum progesterone, with or
      without quantitative beta-human chorionic gonadotropin, is predictive of
      pregnancy outcome within the first 8 weeks of gestation in asymptomatic women.
      STUDY DESIGN: Asymptomatic patients at < 8 menstrual weeks' gestation were
      prospectively evaluated. The enrollment protocol included history, physical
      examination, ultrasonographic confirmation, and blood sample collection for beta
      human chorionic gonadotropin and progesterone. The association between
      progesterone and beta-human chorionic gonadotropin values and pregnancy outcome
      was determined by logistic regression analysis. A receiver-operator
      characteristic curve was generated on the basis of the sensitivity and
      specificity of progesterone results. RESULTS: Seventy-four patients were
      evaluated in this study. The mean serum progesterone level for viable pregnancies
      was 22.1 ng/ml, which was significantly greater than that for the nonviable
      gestations, 10.1 ng/ml (p < 0.001). A single progesterone level was predictive of
      pregnancy outcome (p < 0.001). The probability of an abnormal pregnancy outcome
      with a serum progesterone level < or = 6 ng/ml was 81%. A single beta-human
      chorionic gonadotropin level did not contribute to the prediction of pregnancy
      outcome (p = 0.59). CONCLUSIONS: Serum progesterone alone, within the first 8
      weeks of gestation, is predictive of pregnancy outcome.

PMID- 7520213
TI  - Proliferative response to conserved epitopes of the Chlamydia trachomatis and
      human 60-kilodalton heat-shock proteins by lymphocytes from women with
      salpingitis.
AB  - OBJECTIVE: Our objective was to determine whether an upper genital tract
      Chlamydia trachomatis infection sensitizes lymphocytes to heat-shock protein
      epitopes expressed in both the human and chlamydial 60 kd heat-shock protein.
      STUDY DESIGN: Peripheral blood mononuclear cells were isolated from women with or
      without a prior documented salpingitis and tested for their ability to
      proliferate in response to the recombinant C. trachomatis heat-shock protein and
      to five synthetic peptides corresponding to conserved epitopes expressed in both
      the human and chlamydial heat-shock proteins. RESULTS: Among 22 healthy women
      with no history of chlamydial infections or salpingitis and 10 women seen for
      complaints other than a C. trachomatis infection, none had positive lymphocyte
      responses to any of the peptides and only one responded to the chlamydial heat
      shock protein. Among nine women with a single episode of salpingitis none
      responded to the chlamydial heat-shock protein and one exhibited a positive
      lymphocyte response to a single peptide. This woman was also positive for C.
      trachomatis in the cervix. In contrast, among the 10 women with two or more
      episodes of salpingitis four (40%) had proliferation in response to the
      chlamydial heat-shock protein and five (50%) had positive lymphocyte responses to
      one of the peptides; two of these women also had C. trachomatis detected in their
      cervices. CONCLUSION: In women with a history of C. trachomatis upper genital
      tract infections, infection with C. trachomatis or other microorganisms can
      induce a lymphocyte proliferative response to the chlamydial 60 kd heat-shock
      protein and to epitopes present in the human heat-shock protein.

PMID- 7520214
TI  - Chloride and monovalent ion-selective cation currents activated by oxytocin in
      pregnant rat myometrial cells.
AB  - OBJECTIVE: The purpose of our study was to characterize the membrane mechanisms
      responsible for oxytocin-induced depolarization in single cells from pregnant rat
      myometrium. STUDY DESIGN: Membrane currents were recorded with the whole-cell
      mode of the standard patch-clamp technique. Intracellular calcium concentration
      was monitored with the fluorescence from Fura 2 added to the pipette solution.
      RESULTS: We found that oxytocin predominantly activates potassium, chloride, and
      cation conductances. Chloride and cation currents were evoked by an increase in
      the intracellular calcium concentration dependent on calcium release from the
      heparin-sensitive intracellular stores. Chloride and cation current showed
      different calcium dependences so that they could be activated separately.
      CONCLUSION: Stimulation of oxytocin receptors induces opening of calcium
      activated chloride and cation channels, leading to depolarization of the
      myometrial cells. This depolarization opens, in turn, voltage-dependent calcium
      channels.

PMID- 7520215
TI  - Midtrimester hemoperitoneum caused by placenta percreta in association with
      elevated maternal serum alpha-fetoprotein level.
AB  - We report a case of hemoperitoneum in the second trimester due to placenta
      percreta which was associated with an elevated maternal serum alpha-fetoprotein.
      A 29-year-old woman, gravida 4, para 1-0-2-1, was seen at 17 weeks' gestation
      with an acute abdomen. Maternal serum alpha-fetoprotein in a sample drawn 1 week
      previously revealed a value of 5.0 multiples of the median. At laparotomy,
      placenta percreta was discovered. This case of placenta percreta diagnosed in the
      second trimester was associated with an elevated maternal serum alpha-fetoprotein
      level. Physicians counseling patients with unexplained elevated maternal serum
      alpha-fetoprotein levels should include placenta accreta or percreta in the
      differential diagnosis and should maintain an awareness of its existence in
      patients with acute abdomen in pregnancy.

PMID- 7520216
TI  - Antigenic characterization of Plasmodium vivax with monoclonal antibodies.
AB  - Monoclonal antibodies were produced against Plasmodium vivax obtained from
      patients living in southeastern Mexico, where P. vivax malaria is endemic. Nine
      hybridomas specific for this parasite were obtained. By an indirect
      immunofluorescence assay, seven antibodies were found to react with epitopes
      present in the cytoplasm of the infected erythrocyte and two with the parasite
      itself. By immunoblotting, five monoclonal antibodies reacted with a 17-kD
      protein band, three with an 85-kD band, and two with one of 45 kD. By immunogold
      electron microscopy, two antibodies that reacted with the cytoplasm of infected
      erythrocytes by immunofluorescence also labeled cytoplasmic clefts, and one, in
      addition, recognized caveola-vesicle complexes and the parasite matrix. These
      results demonstrate the value of monoclonal antibodies in identifying P. vivax
      antigens and disclosing their subcellular distribution.

PMID- 7520218
TI  - Extractions reveal specific argentophilic proteins in rat and bull sperm heads.
AB  - BACKGROUND: Silver-stainability (argentophilia) of cytoplasmic structures
      occurring in spermatids have been localized into the organizing perinuclear
      theca, but the biochemical nature and structural associations of these proteins
      with the cytoskeletal and membranous elements are unresolved and, therefore, were
      the aim of the present study. METHODS: Light and electron microscopic analysis of
      the silver-stainability in the rat spermatids and spermatozoa was carried out in
      the intact testis tissue and epididymal spermatozoa and after their chemical and
      mechanical extraction. Correlation of argentophilia with specific proteins of rat
      and bovine spermatids and spermatozoa was investigated using a recently developed
      technique for silver nitrate staining of proteins on nitrocellulose. RESULTS:
      Sequential formation of the silver-stainable domains seemed to proceed from the
      argentophilic acrosomal ring. Various extractions indicated that argentophilia in
      the spermatids and spermatozoa was mainly associated with the perinuclear theca
      and to some extent to the plasma membrane. Hyamine-soluble extract from
      spermatozoa of rat and bull revealed only a single argentophilic protein of 130
      kDa. Hyamine and SDS-soluble extracts of rat testis tissue contained an
      additional group of argentophilic polypeptides of lower molecular weight (115,
      94, 36, 23, and 21 kDa). CONCLUSIONS: Reduction in the number of argentophilic
      proteins appears to be involved in a series of changes in the cyto-architecture
      of developing spermatids. Tentative cytoskeletal nature of argentophilic proteins
      remains to be identified. Nevertheless, they may have important physical
      relations with the higher-order organization of the sperm head cytoskeleton and
      overlying membranes.

PMID- 7520219
TI  - Neuroepithelial bodies in the lung of Basiliscus vittatus (Reptilia, Iguanidae).
AB  - BACKGROUND: Neuro-epithelial bodies (NEB) are corpuscles of currently equivocal
      function which are present in the lungs of vertebrates. Comparative studies may
      help to elucidate their role. METHODS: The NEB of Basiliscus vittatus (Reptilia,
      Iguanidae), a terrestrial lower vertebrate able to dive, are for the first time
      examined by electron microscopy, immunocytochemistry, and for argyrophilia.
      RESULTS: Most NEB contain both immunoreactive calcitonin and serotonin but are
      not labelled with argyrophilia or immunocytochemistry against calcitonin gene
      related peptide (CGRP), protein gene product 9.5 (PGP 9.5), or the Leu-7 epitope
      (Leu-7). Therefore, in NEB of this species, the transcription of the
      calcitonin/CGRP gene exclusively favors the expression of calcitonin and this is
      in contrast to the intrapulmonary small neurons. Also, a physiologic difference
      is expected in the metabolism of ubiquitin in NEB of B. vittatus vs. mammalian
      NEB and neurons. In addition, the NEB cells are always covered by at least a thin
      cytoplasmic extension of a neighbouring cell, indicating that luminal contact is
      not required. Stronger still, it appears that in some lower vertebrates contact
      to the airspace is avoided. Finally, we provide ultrastructural evidence for the
      basket-like innervation of NEB in some reptiles. This way of innervation possibly
      represents an evolutionarily different concept for interaction between NEB
      corpuscular cells and nerve fibers. CONCLUSIONS: Beyond the confirmation that
      morphology, content of biologically active substances such as serotonin and
      calcitonin, and innervation are evolutionary well preserved features of NEB, the
      results reveal some intriguing features of B. vittatus NEB: strict separation of
      calcitonin and CGRP, reduced need for the de-ubiquitinating enzyme PGP 9.5, lack
      of luminal contact, and the basket-like innervation. The latter two properties
      possibly refer to a mechanoreceptor function of NEB in this species.

PMID- 7520220
TI  - Iloprost improves survival of ischemic experimental skin flaps.
AB  - The ability of the prostacyclin analogue iloprost to improve survival of ischemic
      experimental skin flaps was investigated. Unilateral island skin flaps based on
      the superficial inferior epigastric vessels were raised in 70 rats and subjected
      to varying lengths of primary ischemia. The flaps were divided into the following
      four groups: group I, no perfusion washout; group II, postischemic washout with
      lactated Ringer's solution; group III, postischemic washout with urokinase; and
      group IV, postischemic washout with iloprost. Flap survival rates for group IV
      were significantly higher than all other groups (p < 0.05). The primary ischemia
      time at which 50% of the flaps failed was 8.9 hours for group I, 9.5 hours for
      group II, 13.3 hours for group III, and 15.3 hours for group IV. This is the
      first study to investigate the effect of iloprost on skin flap survival. Iloprost
      was found to be significantly more effective than urokinase in salvaging ischemic
      experimental skin flaps.

PMID- 7520217
TI  - A versatile negative-staining ribonuclease zymogram.
AB  - A versatile negative-staining ribonuclease zymogram is described. The method has
      several advantages as it combines, by means of different staining procedures,
      high resolving power, sensitivity, and specificity with a rapid, reproducible,
      and simultaneous analysis of purity of ribonuclease samples on the same
      polyacrylamide gel. Activity bands can be visualized at any time during the
      incubation process without staining of the gel. This allows the choice of
      different staining procedures after incubation. Using poly(C) as substrate less
      than 1 pg of bovine pancreatic ribonuclease A was detected in less than 2 h after
      the electrophoretic run. An additional advantage with respect to other methods is
      that no refrigeration is needed during electrophoresis.

PMID- 7520221
TI  - [A case of AFP (alpha-fetoprotein) producing gastric cancer successfully treated
      with EAP (etoposide, adriamycin, cisplatin) therapy].
AB  - A case of AFP producing gastric cancer successfully treated with EAP therapy is
      reported with a review of the literature. A 56-year-old male was admitted
      complaining of epigastralgia and back pain. He was diagnosed as having a gastric
      cancer with multiple liver metastases by endoscopy and computed tomography. Serum
      AFP level was 2,791,000 ng/ml and biopsy specimen showed AFP-positive tumor cells
      by PAP (peroxidase-antiperoxidase) method in hepatoid structure. Preoperative
      combination chemotherapy with etoposide, adriamycin and cisplatin resulted in a
      remarkable decrease in serum AFP level. Subtotal gastrectomy (R3) with hepatic
      artery cannulation was performed. The therapeutic effect by histological
      examination showed Grade 3 in the primary site and Grade 2 in both resional lymph
      nodes and liver metastasis.

PMID- 7520222
TI  - [Ventricular premature contraction observed after anti-cancer chemotherapy with
      ifosfamide].
AB  - We encountered 3 cases of ventricule premature contraction (VPC) after anti
      cancer chemotherapy with ifosfamide (IFM). These cases were administered IFM of
      more than 2 g/body/day for 3 days, and they were more than 70 years old. They had
      no cardiovascular disorder before the chemotherapy. Among them, 1 case who
      received a total dose of 15.0 g of IFM showed severe VPC. She had also received a
      total dose of 155 mg of doxorubicin (ADM) in earlier treatment. There was also 1
      case, whose VPC was aggravated after anti-cancer chemotherapy with IFM. He had
      dilated cardiomyopathy and had already showed frequent VPC before the
      chemotherapy. His VPC became more frequent after the chemotherapy. IFM was a
      common agent among the anti-cancer agents used in these cases. We must be careful
      for the occurrence of VPC when more than 2 g/body/day of IFM is administered to
      patients more than 70 years old. An increase in the total dose of IFM or former
      ADM may cause severe VPC. When IFM is given a patient with VPC, the existing VPC
      may be aggravated.

PMID- 7520223
TI  - [A pilot study of alternate combination chemotherapy with rhG-CSF for adult T
      cell leukemia/lymphoma].

PMID- 7520225
TI  - Expression of c-kit ligand in human keratinocytes.
AB  - The c-kit ligand is expressed on tissue-anchored stromal cells. It plays an
      important role in the development of c-kit-bearing cells, such as haematopoietic
      cells, germ cells, mast cells and melanocytes. In the present study, we used the
      reverse transcriptase-mediated polymerase chain reaction (PCR) technique to
      investigate whether human keratinocytes are able to express c-kit ligand mRNA.
      Two sets of primers were designed to distinguish two types of c-kit ligand mRNA
      (full-length type and spliced type). One set was used to amplify an 882-bp DNA
      fragment from the full-length type, and a 798-bp DNA fragment from the spliced
      type. Another set was used to amplify a 375-bp DNA fragment from the full-length
      type only. A cDNA fragment corresponding to the full-length type mRNA was
      amplified from a cDNA preparation of cultured human keratinocytes as well as from
      epidermis obtained by the suction blister technique. This result indicates the
      spontaneous transcription of full-length type mRNA of the c-kit ligand in human
      keratinocytes.

PMID- 7520224
TI  - The role of proteases in stratum corneum: involvement in stratum corneum
      desquamation.
AB  - The effects of protease inhibitors on cell dissociation were studied in vitro in
      order to examine the involvement of proteases in stratum corneum desquamation.
      Stratum corneum sheet (peeled from human backs after sunburn) was incubated in a
      detergent mixture containing 8 mM N,N-dimethyldodecylamine oxide, 2 mM sodium
      lauryl sulphate and 60 micrograms/ml kanamycin with or without protease
      inhibitors, and the number of released cells was counted after incubation for 48
      h. Cell dissociation was inhibited strongly by antipain or aprotinin, but not at
      all by N-[N-(L-3-transcarboxyoxiran-2-carbonyl)-L-leucyl]-agmatin, N
      ethylmaleimide or pepstatin, which suggests that only serine proteases are
      associated with desquamation. Furthermore, leupeptin and chymostatin each reduced
      cell dissociation about half as effectively as aprotinin or antipain, while a
      mixture of leupeptin and chymostatin prevented stratum corneum dissociation as
      potently as antipain or aprotinin. In addition, the activity of chymotrypsin-like
      protease in scaly skin was higher than that in normal skin, as we have previously
      found for trypsin-like protease. These results suggest that both trypsin-like and
      chymotrypsin-like serine proteases are involved in stratum corneum desquamation.

PMID- 7520227
TI  - [Leukemogenic risk during long-term use of G-CSF in constitutional neutropenia].

PMID- 7520228
TI  - Bone marrow aspirate immunofluorescent and bone marrow biopsy immunoperoxidase
      staining of plasma cells in histologically occult plasma cell proliferative
      marrow disorders.
AB  - Immunofluorescent staining (immunofluorescence bone marrow aspirate) and
      immunoperoxidase staining (immunoperoxidase bone marrow biopsy) were compared in
      26 patients with plasma cell dyscrasia and less than 10% marrow plasma cells.
      Their clinical diagnoses included monoclonal gammopathy of undetermined
      significance (13 patients), treated multiple myeloma (four patients), multiple
      myeloma with less than 10% marrow plasma cells (two patients), primary systemic
      amyloidosis (two patients), monoclonal gammopathy of undetermined significance
      with neuropathy (two patients), angiofollicular lymph node hyperplasia (two
      patients, all with the POEMS [polyneuropathy, organomegaly, endocrinopathy,
      monoclonal protein, and skin changes] syndrome), and primary (amyloidosis)
      amyloid neuropathy (one patient). The percentage of plasma cells was greater than
      5% in 23% of patients and less than or equal to 5% in 77% of patients. With
      immunofluorescence bone marrow aspirate and immunoperoxidase bone marrow biopsy,
      light-chain restriction was demonstrated in 84% of all cases and accurately
      determined in 96% of all cases as shown by serum and urine paraprotein analysis
      or tissue amyloid typing. Monoclonal populations of plasma cells can be readily
      identified with immunofluorescence bone marrow aspirate and immunoperoxidase bone
      marrow biopsy in most patients with paraproteins and marrow plasmacytoses not
      diagnostic of multiple myeloma.

PMID- 7520226
TI  - Histogenesis and possible mechanism of chondroid changes in mixed tumour of the
      skin: immunohistochemical evaluation of bone morphogenetic protein,
      glycosaminoglycans, keratin, vimentin and neuronal markers.
AB  - The distribution of immunoreactivity of bone morphogenetic protein (BMP), the
      glycosaminoglycans chondroitin 4-sulphate (C4SPG), chondroitin 6-sulphate
      (C6SPG), dermatan sulphate (DSPG) and keratan sulphate proteoglycans (KSPG),
      cytokeratin (K8.12), vimentin, glial fibrillary acidic protein (GFAP), actin,
      desmin, S-100 protein and neuron-specific enolase (NSE) in mixed tumour of the
      skin was investigated using immunohistochemical methods using monoclonal (MoAb)
      and polyclonal antibodies (PoAb). A strong BMP immunoreactivity was found
      characteristically in outer tumour cells of tubuloductal structures and modified
      myoepithelial cells. Modified myoepithelial cells and chondroidally changed cells
      showed positive immunoreactivity for C4SPG, C6SPG and DSPG; and KSPG was more
      pronounced in the modified myoepithelial cells. Vimentin, S-100 protein, GFAP and
      NSE, but not actin and desmin, were distribute in the outer tumour cells and
      modified myoepithelial cells in chondroidally changed tissue. Two factors show
      that chondrogenesis in mixed tumour of the skin is associated with the modified
      myoepithelial cells through the activity of BMP and biosynthesis of
      glycosaminoglycans as matrix substance. First, outer or basal tumour cells in
      mixed tumour of the skin is characterized by the presence of positive
      immunoreactivity for BMP, KSPG, vimentin, cytokeratin K8.12, S-100 protein, GFAP
      and NSE, and second, there is a matrix of chondroidally changed tissue containing
      the reaction products of C4SPG, C6SPG, DSPF and KSPG.

PMID- 7520229
TI  - The fate of glycogen in granular tubule cells of rat submandibular glands during
      secretory events.
AB  - Glycogen, studied electron microscopically in granular tubule cells by means of
      the periodic acid-thiocarbohydrazide-silver proteinase technique, was found to be
      scattered abundantly throughout the cytoplasm. Parasympathetic nerve stimulation
      caused no detectable change in the glycogen. Degranulation of the granular tubule
      cells after either sympathetic nerve stimulation or cyclocytidine injection
      caused loss of the glycogen from the cells. Study of tubule cells undergoing
      secretion in the early stages after cyclocytidine injection indicated that
      glycogenolysis was occurring. Glycogen had reaccumulated in the cells within 24
      h, before extensive reformation of the secretory granules had occurred, and
      remained abundant throughout the subsequent granule formation. It is concluded
      that glycogen provides an important source of energy during secretory
      degranulation of the granular tubule cells.

PMID- 7520230
TI  - Why palliative care?
AB  - And so there we have it in a nutshell--palliative care is about caring. Caring
      for those who are dying and for those who look after them and then grieve their
      loss. Palliative care has risen like a phoenix from the ashes of neglect and bad
      management which, until recently, had been the lot of the dying. Perhaps this new
      specialty may become a guiding beacon leading a profession, somewhat bewitched
      and side tracked by its own scientific cleverness, back to the road of caring. I
      sincerely hope that as the specialty gains recognition it does not lose its
      present identify and fine sense of purpose.

PMID- 7520231
TI  - The role of the general practitioner in palliative care.
AB  - Palliative care tests the general practitioner's generalist skills. The work is
      not easy. We are trying to control symptoms that progress, feeling at times like
      the driver of a car with no brakes. It can evoke emotions of disturbing
      intensity. However, it is intensely rewarding work as well. The privilege of
      sharing life's journey with a patient, helping to enhance his or her quality of
      life, is one open to very few in our society. It is a privilege we should eagerly
      accept, as we are invited to stand with our patients facing their final
      challenge.

PMID- 7520232
TI  - Managing anger in palliative care.
AB  - Anger is a commonly encountered emotion in the cancer setting. Understanding its
      origin is vital but the practitioner needs to facilitate more than the
      ventilation of feelings; some change in attitude, the provision of social support
      and the promotion of adaptive coping need to be generated. The perceived
      unfairness of illness and death commonly underpins anger in the patient with
      cancer. Management strategies are discussed.

PMID- 7520233
TI  - Palliative care in the home. The GP/home hospice team.
AB  - The family doctor has always had a significant role in caring for terminally ill
      patients. Giving support to patients in their last few weeks or hours of life can
      be an emotionally demanding, clinically frustrating, time-consuming task. The
      advent of home palliative care services has given patients, families and doctors
      access to a home hospice team that can provide invaluable support.

PMID- 7520235
TI  - Pain forum. Part 2. Neuropathic pain.
AB  - Neuropathic pain is often a reason for an unfavourable response to morphine or
      other opioids in treating cancer pain. This type of pain is difficult to manage
      and may co-exist with nociceptive cancer pain. There is still a potential for
      opioid responsiveness, although the doses needed will be higher, and adjuvant
      drug therapies are best employed concurrently with opioid drugs. Adjuvant drugs
      used are the antidepressants, anticonvulsants, including benzodiazepines,
      corticosteroids and neurolepts. Less commonly, agents such as baclofen and
      clonidine, and sympatholytic drugs such as prazosin can be employed for
      sympathetically maintained neuropathic pain (discussed in Part 3). The type of
      agent selected will depend on the natural history of the disease process, as well
      as a description of the pain--the lancinating pains tending to respond better to
      anticonvulsants. Non invasive neurostimulatory approaches such as transcutaneous
      electrical nerve stimulation (TENS) may be useful in management, and a few
      patients may require an invasive procedure such as dorsal column stimulation.

PMID- 7520234
TI  - Pain forum. Part 1. Nociceptive cancer pain.
AB  - The components of a holistic pain assessment process in advanced cancer are
      presented. Central to the assessment and management process is recognition of
      different types of cancer pain, which have their own individual management
      emphasis. An overview of nociceptive cancer pain management is presented
      outlining current drugs available and the 'analgesic ladder' approach.

PMID- 7520236
TI  - Differential regulation of mu- and m-calpain in rat hearts perfused with Ca2+ and
      cAMP.
AB  - Reversible interconversion between calpastatin I and calpastatin II, the
      phosphorylated form of the inhibitor, has been induced in rat heart perfused with
      the combination Ca2+/A23187 ionophore or with cAMP. In the presence of the
      ionophore and increasing concentrations of Ca2+, calpastatin II is converted into
      calpastatin I; whereas the reverse reaction is induced by the addition of cAMP.
      Both interconversions leave substantially unmodified the amount of calpastatin I
      which inhibits mu-calpain with higher efficiency and accordingly keeps the
      proteinase in an permanent inactive state. On the contrary, expression of m
      calpain activity is significantly repressed or alternatively largely augmented as
      a result of a profound increase or decrease in the level of calpastatin II
      induced by perfusion with cAMP or with Ca2+/ionophore respectively. Taken
      together our results demonstrate that bidirectional interconversion can take
      place in rat heart cells and through this mechanism the activity of m-calpain can
      be efficiently controlled. Ca2+ ions and cAMP are temptatively proposed as the
      natural stimuli responsible for the modulation of this overall process.
      Experimental evidences are provided indicating that the transition to the active
      form of mu-calpain involves association to the plasma membrane, a process
      competitively antagonized by calpastatin I; thus suggesting that interaction with
      one or the other ligand can affect the intracellular ratio between inactive and
      active mu-calpain forms.

PMID- 7520237
TI  - Cloning and phylogenetic analysis of the core, E2, and NS3/NS4 regions of the
      hepatitis C virus type 5a.
AB  - By means of the Line Probe Assay, a hepatitis C virus type 5a infected serum from
      a Belgian patient was selected. The complete core region (573 bp), the
      carboxyterminal part of E1 and the aminoterminal part of E2/NS1 (661 bp), and an
      epitope containing region in NS3-NS4 (1452 bp) were cloned and sequenced. The
      deduced amino acid sequence revealed type-specific variations in regions of core
      and NS4 which were previously recognized as evoking a type-specific antibody
      response. In addition, the aminoterminal region of E2 showed high variability
      when compared with sequences of type 1, 2, and 3. Phylogenetic analysis showed
      separate branching of this isolate. The analysis in the core region was not
      conclusive for some of the strains included and should therefore be carried out
      in combination with the NS5B region.

PMID- 7520238
TI  - Thiabendazole is an inducer of cytochrome P4501A1 in cultured rabbit hepatocytes.
AB  - The effect of TBZ (30-100 microM) was investigated on cytochromes P450 of
      cultured rabbit hepatocytes considered 72 h after plating. At the highest
      concentrations and without apparent cellular toxicity, the drug provokes a dose
      dependent increase in total microsomal cytochrome P450 and a rise in EROD
      activity which was correlated to a specific increase in P4501A1 level. Northern
      blot analysis of RNA reveals an increased level of mRNA specific to P4501A1. The
      transcriptional activation of this isoenzyme is proposed because of the
      significant inhibition of the above-mentioned increases when actinomycin was
      added to the culture medium. Data obtained from competition experiments
      demonstrate that TBZ is not a ligand of Ah receptor. A down-regulation process
      could explain the slight decrease in both ANOH and P4502E1 level observed in
      hepatocytes treated with the highest dose of TBZ.

PMID- 7520239
TI  - Extracellular ATP increases NH4+ permeability in human lymphocytes by opening a
      P2Z purinoceptor operated ion channel.
AB  - The permeability of lymphocytes to NH4+ was examined by measuring intracellular
      pH using the fluorescent pH-sensitive dye BCECF. Addition of 20 mM NH4Cl produced
      a rapid phase of alkalinization. This was followed by a slow return to resting
      pHi due to NH4+ influx. The rate of NH4+ was increased many fold by extracellular
      ATP and the increment showed features consistent with NH4+ being a permeant for
      the P2Z purinoceptor operated ion channel. Cytosolic pH measurements showed
      monomethylammonium+ and dimethylammonium+ were also permeants, but
      trimethylammonium+ (69 Dalton) was excluded by this channel. Since our previous
      data showed ethidium+ (314 Dalton) is a permeant it appears that molecular
      conformation rather than molecular weight determines entry of cationic solutes
      through the channel.

PMID- 7520240
TI  - Noncytopathic strains of bovine viral diarrhea virus prime bovine bone marrow
      derived macrophages for enhanced generation of nitric oxide.
AB  - Bovine bone marrow-derived macrophages (BBMM) were infected in vitro with a
      cytopathic (cp) and a noncytopathic (ncp) biotype of bovine viral diarrhea virus
      (BVDV). The virus strains used, TGAN (ncp) and TGAC (cp), originate from one
      animal and are antigenically closely related. Both TGAC and TGAN infected a
      subset of BBMM. Only cp BVDV induced a cytopathic effect. Infection of BBMM
      resulted in the modulation of certain macrophage functions. Only ncp strains of
      BVDV primed BBMM for enhanced reactive nitrogen production in response to
      Salmonella dublin. In contrast, infection with both biotypes did not influence
      bacteria-induced procoagulant activity and both biotypes equally reduced PMA
      induced superoxide production. This suggests that the two biotypes differentially
      and selectively affect certain macrophage functions related to host defense. For
      the first time, a BVDV biotype-associated difference has been related to a
      biochemical parameter of the host cell.

PMID- 7520241
TI  - A new point mutation at nucleotide pair 3291 of the mitochondrial tRNA(Leu(UUR))
      gene in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis,
      and stroke-like episodes (MELAS).
AB  - A new point mutation at nucleotide pair 3291 in the mitochondrial tRNA-Leu(UUR)
      gene was found in a Japanese MELAS patient. The nucleotides at the mutated site
      were evolutionarily invariant from humans through sea urchins. The mutant genomes
      were detected in a heteroplasmic fashion in muscle and blood cells of the proband
      by means of PCR-RFLP. Among 46 MELAS, 5 MERRF, 23 CPEO and 55 normal controls
      examined, this is the only patient with the mutation. This is the third mutation
      associated with MELAS in addition to nucleotides at 3243 and 3271. All three
      mutations occurred within the tRNA-Lue(UUR) region indicating that the tRNA
      alteration is responsible for the MELAS phenotype.

PMID- 7520242
TI  - Fine motor deficit: an etiologically distinct entity.
AB  - The prevalence of risk and adverse factors associated with fine motor disorder (n
      = 35) were compared with gross motor deficit (n = 158), global developmental
      delay (n = 336), and combined fine and gross motor deficit among 1,241 children
      up to 3 years of age identified in the Haifa health district. A significantly
      increased preponderance of males was observed among the study group as compared
      to the group with gross motor deficit. Intranatal problems were significantly
      increased among children with fine motor deficits as compared to those with gross
      motor deficits as were minor physical anomalies, seizures, and behavioral
      deficits. Less significant differences were observed between the study group and
      children with global developmental delay or fine and gross motor deficit. The
      different risk factor profiles indicated that the children with fine motor
      deficits constituted an etiologically distinct group highly associated with early
      antepartum, possibly genetic, origins.

PMID- 7520243
TI  - [Prognostic value of electrodiagnosis of Bell's palsy].
AB  - Many papers report on a poor rate of complete restitution of Bell's palsy if
      signs of degeneration can be detected in neuromyography (NMG) or electromyography
      (EMG). In 119 patients who underwent infusion therapy (as developed by Stennert)
      39% showed signs of degeneration in EMG or NMG. Complete restitution was achieved
      in 93% of these patients. Degeneration was more frequent in elderly patients (<
      20 years: 20%, > 60 years: 55%). This did not affect the rate of complete
      restitution, which was constantly high for every age. If infusion therapy was
      started within 7 days after onset of the disease, no defects in restitution were
      observed, which was frequently so if therapy was started later. After one year
      the rate of complete restitution was about equal in cases with signs of
      degeneration (91%) and non-degenerative cases (94%). But 80% of the non
      degenerative cases showed complete restitution within 3 months after onset of the
      palsy, whereas 80% of cases with signs of degeneration healed after this date
      (mean 6.1 months). After oral therapy with cortisol exclusively half of the
      degenerative cases did not attain complete restitution. After infusion therapy
      EMG and NMG do not answer the question if a Bell's palsy will heal completely or
      not but enable us to predict when this will probably be the case.

PMID- 7520244
TI  - [Neurogenic inflammation and area of involvement of the facial nerve of the rat].
AB  - Antidromic electrical stimulation of sensory nerves produces vascular
      hyperpermeability, plasma protein extravasation and oedema. The initial phase of
      this inflammatory reaction is induced by the release of the neuropeptides CGRP,
      SP and NKA; the later phase is induced by mast cells. In previous investigations
      we were able to show that the facial nerve of the rat contains CGRP, SP and NKA
      as well as mast cells. The same mechanism--increased vascular permeability-
      plasma extravasation--oedema--is thought to be part of the pathogenesis of Bell's
      palsy. Hence, we tried to produce neurogenic inflammations in the facial nerves
      of six adult Wistar rats. To assess plasma extravasation we used Evans blue, a
      dye which binds to serum albumin, according to the method described by Brokaw and
      White (1992). Having cut the facial nerve distal of the stylomastoid foramen we
      induced a neurogenic inflammation by the application of an electrical stimulus to
      the distal part of the nerve. In comparison to the contralateral, non-stimulated
      side, we recognized that the inflammatory reactions were limited to the area of
      the skin innervated by the posterior auricular nerve. So far, we can transfer
      this "neurogenic inflammation model" the well-known relationship between nerves
      and inflammatory reactions to this limited area innervated by the facial nerve.

PMID- 7520245
TI  - Differential accumulation of insulin-like growth factor-I in kidneys of pre- and
      postpubertal streptozotocin-diabetic rats.
AB  - Nephropathy, one of the major complications of diabetes mellitus, is
      characterized by an early increase in kidney size. In experimental models of
      diabetes, this event is preceded by a rapid and transient rise in kidney IGF-I
      levels, at least in adult animals. Since diabetes-associated renal changes are
      uncommon in young patients, we investigated the early changes in the components
      of the IGF system following induction of diabetes in prepubertal and postpubertal
      rats. The rationale for this study was the evaluation of potential differences
      which could lead to kidney complications only at adult stages. Unlike the
      situation in the postpubertal kidney, in which there was a transient accumulation
      of extractable IGF-I 24-48 h after streptozotocin (STZ) administration, there was
      a decrease of approximately 12-fold in the level of IGF-I in the prepubertal
      kidney over the same period of time. Paradoxically, kidney IGF-I mRNA levels were
      reduced by approximately 50% in the postpubertal rat 24 h after STZ treatment,
      whereas in the prepubertal kidney IGF-I mRNA levels were unaltered. Furthermore,
      the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding to kidney
      membranes of postpubertal diabetic rats were similar to the levels in control
      kidneys. On the other hand, both the levels of IGF-I receptor mRNA and 125I
      labelled IGF-I binding were increased (approximately 2.5-fold (after 24 h) and
      approximately 3-fold (after 48 h) respectively) in prepubertal animals. In
      addition, increased expression of IGF-binding protein (IGFBP)-1 mRNA was seen
      early in diabetes in both pre- and postpubertal rats. The results of this study
      suggest that the transient accumulation of IGF-I in the kidney of the
      postpubertal diabetic rat may not be due to an increase in the local synthesis of
      IGF-I, but rather to an increase in IGF-I uptake from the circulation due to non
      membrane-associated IGFBP-1. The lack of accumulation of IGF-I in the prepubertal
      kidney probably reflects the approximately 10-fold lower levels of circulating
      IGF-I in young as compared with adult diabetic rats.

PMID- 7520246
TI  - Efficacy of the biparietal diameter/femur length ratio to detect Down syndrome in
      patients with an abnormal biochemical screen.
AB  - Abnormal fetal biometry is considered a marker for fetal trisomy. We
      prospectively evaluated the biparietal diameter/femur length ratio to identify
      Down syndrome fetuses. This ratio was calculated when women (< 35 years old)
      underwent an amniocentesis for an abnormal biochemical screen for Down syndrome.
      Using reported ratio cut-offs (> 1.5 SD above the mean), the ratio had a
      sensitivity of 50% (3/6), specificity of 92% (244/264), positive predictive value
      of 13% (3/23), negative predictive value of 99% (244/247), and a relative risk of
      10.8. Using our own population ratio, a cut-off > 1.5 SD had a sensitivity of 50%
      (3/6), specificity of 94% (249/252), positive predictive value of 17% (3/18),
      negative predictive value of 99% (249/252) and a relative risk of 13.9. A lower
      cut-off decreased the efficacy to detect Down syndrome. A ratio > 1.5 SD above
      the mean is a useful adjunct to identify Down syndrome in pregnancies at risk by
      an abnormal biochemical screen.

PMID- 7520247
TI  - Characterization of a human Kaposi's sarcoma cell line that induces angiogenic
      tumors in animals.
AB  - OBJECTIVE: To characterize a Kaposi's sarcoma (KS) cell line established from a
      tumor biopsy from the oral mucosa of an iatrogenically immunosuppressed HIV
      negative man. METHODS: Cells were placed in culture and evaluated by a variety of
      biologic, serologic, karyotypic, and immunologic procedures. Electron microscopic
      examination was performed. The ability to produce tumors in nude mice was
      evaluated, and the nature of the cells within the tumor determined. Assays for
      urokinase plasminogen activator type (uPA), plasminogen activator inhibitor-1
      (PAI-1) and the urokinase receptor (uPAR) were conducted. RESULTS: The SLK cell
      line has an endothelial cell morphology with very little anaplasia. The karyotype
      indicates diploid phenotype of human origin. Immunohistochemical and electron
      microscopic examinations confirmed the endothelial nature of this cell line. No
      viruses were detected. The tumors induced in nude mice showed
      hypervascularization, with characteristics of KS. The cell line produces uPA and
      PAI-1, and also expresses uPAR. CONCLUSIONS: The SLK cell line is of endothelial
      cell origin and the first human cell line to induce KS-like tumors in recipient
      animals. The expression of urokinase and its receptor suggests a paracrine and
      autocrine interaction that may be important for the growth of the tumor. The SLK
      line should be valuable for studies of KS pathogenesis and therapeutic approaches
      to this malignancy.

PMID- 7520248
TI  - Comparison of the immune response to recombinant gp120 in humans and chimpanzees.
AB  - OBJECTIVE: To assess similarities and differences in antibody responses to
      recombinant (r) HIV-1IIIB gp120 in chimpanzees, previously protected from HIV-1
      infection, and human volunteers immunized in connection with a Phase I clinical
      trial. METHODS: Frozen sera from humans immunized with rgp120 from HIV-1IIIB and
      chimpanzees immunized with the same antigen or recombinant soluble gp160 were
      compared in a variety of serologic assays. RESULTS: The magnitude of the antibody
      response to gp120 was similar in both species; however, the half-life of the
      antibody response to rgp120 was approximately 4.5 times longer in humans (9
      weeks) than in chimpanzees (2 weeks). Antibodies to gp120 in both species were
      broadly cross-reactive with gp120 from diverse isolates of HIV-1 and were
      effective in blocking the binding of gp120 to CD4. Antibody binding to native
      gp120 was greater than to denatured gp120 in both species. Antibody responses to
      the principal neutralizing determinant (V3 domain) and virus neutralization
      titers were approximately 10-fold lower in humans than chimpanzees. The relative
      avidity of antibody binding to gp120 was higher in the sera from the immunized
      chimpanzees than in the immunized humans. CONCLUSIONS: While the antibody
      responses to rgp120 elicited in man and chimpanzees were in many ways similar,
      significant differences did occur. Predictions made on the basis of chimpanzee
      immunogenicity studies over-estimated the potency of the virus neutralizing
      titers and under-estimated the duration of the antibody response achieved in
      humans.

PMID- 7520249
TI  - A 12-month study of the effects of oral zidovudine on neurodevelopmental
      functioning in a cohort of vertically HIV-infected inner-city children.
AB  - OBJECTIVE: To examine the effects of oral zidovudine on the neurodevelopmental
      functioning of HIV-infected children. METHODS: Oral zidovudine was administered
      to 54 symptomatic children with vertically transmitted HIV infection (Centers for
      Disease Control and Prevention class P2). All children were recruited from an
      inner-city pediatric HIV/AIDS outpatient clinic and ranged in age from 2 months
      to 12 years and 11 months (mean age, 3 years) at entry. Neurodevelopmental
      functioning, height and weight, and lymphocyte subpopulation data were
      ascertained for all the children pretherapy, and 6 and 12 months post-therapy
      initiation. RESULTS: Analysis of the 6- and 12-month post-initiation drug data
      found no significant change in neurodevelopmental functioning. Height and weight
      percentiles remained the same or improved in the majority of children. CD4+ cell
      counts declined over the treatment period with CD4+ counts < 500 x 10(6)/l
      observed in 15% of the children pre-therapy, and 33% after 1 year. CONCLUSION: In
      contrast with previously published data, the present study observed no
      improvement in neurodevelopmental functioning in HIV-infected children treated
      with oral zidovudine.

PMID- 7520250
TI  - Modulation of integrins expression during human osteoblasts "in vitro"
      differentiation.
AB  - We here report the modulation of the adhesion of cultured human osteoblasts on
      Laminin during the acquisition of differentiated phenotype. We also show that
      interference with the differentiation program caused by treatment with Retinoic
      acid of the cultures, causes changes of the capability to adhere to Laminin and
      type I Collagen. The younger or dedifferentiated cells have lower capability to
      bind to Laminin or Collagen. The maturation associated changes are specific for
      the adhesion to the above substrata and do not involve the adhesion to FN or
      plastic. The alpha subunit(s) of the integrin receptor(s) for these proteins is
      likely to be responsible for the modulation adhesion to Laminin and Collagen.

PMID- 7520251
TI  - Nitric oxide mediates the formation of synaptic connections in developing and
      regenerating olfactory receptor neurons.
AB  - Nitric oxide (NO) is a diffusible free radical that functions as a second
      messenger and neurotransmitter. NO synthase (NOS) is highly and transiently
      expressed in neurons of the developing olfactory epithelium during migration and
      establishment of primary synapses in the olfactory bulb. NOS is first expressed
      at E11 in cells of the presumptive nervous layer of the olfactory placode. NOS
      immunoreactivity persists in the descendants of these cells that differentiate
      into embryonic olfactory receptor neurons (ORNs). Olfactory NOS expression in the
      ORN and in its afferents rapidly declines after birth and is undetectable by P7.
      Following bulbectomy, NOS expression is rapidly induced in the regenerating ORN
      and is particularly enriched in their outgrowing axons. Immunoblot and Northern
      blot analyses similarly demonstrate an induction of NOS protein and mRNA
      expression, respectively, the highest levels of which coincide with peaks of ORN
      regeneration. These data argue against a role for NO in odorant-sensitive signal
      transduction, but suggest a prominent function for NO in activity-dependent
      establishment of connections in both developing and regenerating olfactory
      neurons.

PMID- 7520253
TI  - Modulation of ion channels in rod photoreceptors by nitric oxide.
AB  - Subcellular compartments in the outer retina of the larval tiger salamander were
      identified as likely sites of production of nitric oxide (NO), a recently
      recognized intercellular messenger. NADPH diaphorase histochemistry and NO
      synthase immunocytochemistry labeled photoreceptor ellipsoids and the distal
      regions of bipolar and glial cells apposing photoreceptor inner segments,
      suggesting a role for NO in visual processing in the outer retina. We
      investigated the actions of NO on several rod photoreceptor ion channels.
      Application of the NO-generating compound S-nitrosocysteine increased Ca2+
      channel current and a voltage-independent conductance, but had no affect on
      voltage-gated K+ or nonspecific cation currents. Given the steep relation between
      voltage-dependent Ca2+ influx and photoreceptor synaptic output, these results
      indicate that NO could modulate transmission of the photoresponse to second order
      cells.

PMID- 7520252
TI  - Transient nitric oxide synthase neurons in embryonic cerebral cortical plate,
      sensory ganglia, and olfactory epithelium.
AB  - Neuronal nitric oxide synthase (NOS), visualized immunohistochemically or with
      NADPH diaphorase histochemistry, is transiently expressed in discrete areas of
      the developing rat nervous system. In the brain transient NOS expression occurs
      in the cerebral cortical plate. At E15-E19, the majority of cells in the plate
      stain, with their processes extending through the corpus striatum to the
      thalamus. This staining decreases after birth and vanishes by the 15th postnatal
      day. Neurons in olfactory epithelium also express NOS from E15 till early
      postnatal life. In embryonic sensory ganglia virtually all neuronal cells are NOS
      positive, whereas by early adulthood only 1% express NOS. By contrast to these
      areas of transient NOS expression, in other neuronal sites NOS staining appears
      after cell bodies cease dividing and cells extend processes, and the staining
      persists in adult life. The transient expression of neuronal NOS may reflect a
      role in developmental processes such as programmed cell death.

PMID- 7520254
TI  - Molecular cloning and characterization of retinal photoreceptor guanylyl cyclase
      activating protein.
AB  - Guanylyl cyclase-activating protein (GCAP) is thought to mediate Ca(2+)-sensitive
      regulation of guanylyl cyclase (GC), a key event in recovery of the dark state of
      rod photoreceptors following light exposure. Here, we characterize GCAP from
      several vertebrate species by molecular cloning and provide evidence that GCAP
      contains a heterogeneously acylated N-terminal region that interacts with GC.
      Vertebrate GCAPs consist of 201-205 amino acids, and sequence analysis indicates
      the presence fo three EF hand Ca(2+)-binding motifs. These results establish that
      GCAP is a novel photoreceptor-specific member of a large family of Ca(2+)-binding
      proteins and suggest that it participates in the Ca(2+)-binding proteins and
      suggest that it participates in the Ca(2+)-sensitive activation of GC.

PMID- 7520255
TI  - Glial cell degeneration and hypomyelination caused by overexpression of myelin
      proteolipid protein gene.
AB  - Myelin proteolipid protein (PLP), the major myelin protein in the CNS, has been
      thought to function in myelin assembly. Thus, mutations within the gene coding
      for PLP (Plp) cause hypomyelination, such as the jimpy phenotype in mice and
      Pelizaeus-Merzbacher disease in humans. However, these mutants often exhibit
      premature death of oligodendrocytes, which form CNS myelin. To elucidate the
      functional roles of Plp gene products in the maturation and/or survival of
      oligodendrocytes, we produced transgenic mice overexpressing the Plp gene by
      introducing extra wild-type mouse Plp genes. Surprisingly, transgenic mice
      bearing 4 more Plp genes exhibited dysmyelination in the CNS, whereas those with
      2 more Plp genes showed normal myelination at an early age (3 weeks after birth),
      but later developed demyelination. Overexpression of the Plp gene resulted in
      arrested maturation of oligodendrocytes, and the severity of arrest was dependent
      on the extent of overexpression. Overexpression also led to oligodendrocyte cell
      death, apparently caused by abnormal swelling of the Golgi apparatus. Thus, tight
      regulation of Plp gene expression is necessary for normal oligodendrocyte
      differentiation and survival, and its overexpression can be the cause of both dys
      and demyelination.

PMID- 7520256
TI  - Selective potentiation of NMDA-induced neuronal injury following induction of
      astrocytic iNOS.
AB  - Nitric oxide (NO) produced by the constitutive NO synthase (cNOS) in neurons has
      been implicated in mediating excitotoxic neuronal death. In our murine cortical
      cell culture system, NMDA neurotoxicity was not blocked by addition of the NOS
      inhibitors, NG-nitro-L-arginine or aminoguanidine. However, following activation
      of inducible NOS in astrocytes by interleukin-1 beta plus interferon-gamma, NMDA
      but not kainate neurotoxicity was markedly potentiated. This selective
      potentiation of NMDA neurotoxicity was blocked by NOS inhibition or antioxidants
      (superoxide dismutase/catalase or Tempol) and could be mimicked by NO generators
      (SIN-1 or SNAP) or the oxygen radical generator, pyragallol. These results raise
      the possibility that NO production by astrocytes may contribute to NMDA receptor
      mediated neuronal death, perhaps through interaction with oxygen radicals.

PMID- 7520257
TI  - Changes in end-tidal carbon dioxide during gynecologic laparoscopy: spontaneous
      versus controlled ventilation.
AB  - STUDY OBJECTIVE: To study the changes in PETCO2 during spontaneous and controlled
      ventilation in patients undergoing gynecologic laparoscopy. DESIGN: Randomized,
      unblinded study. SETTING: Department of Gynecology, University Hospital,
      Linkoping, Sweden; Central Hospital, Norrkoping, Sweden. PATIENTS: Forty healthy
      patients undergoing gynecologic laparoscopy. INTERVENTIONS: Patients were divided
      into 4 groups: Group 1 breathed spontaneously via an endotracheal tube, while the
      other three groups underwent controlled ventilation to an initial PETCO2 of 3 kPa
      (22 mmHg) (Group 2), 4 kPa (30 mmHg) (Group 3), or 5 kPa (37 mmHg) (Group 4).
      MEASUREMENTS AND MAIN RESULTS: PETCO2 levels were measured at fixed time
      intervals. Arterial blood gas analyses were done to compare the difference
      between PETCO2 and PaCO2. In Group 1, PETCO2 increased soon after insufflation
      and remained above 6 kPa (44 mmHg) throughout the procedure. In Groups 2, 3, and
      4, PETCO2 also rose after insufflation, and an initial PETCO2 of 4 kPa (30 mmHg)
      was ideal, as all PETCO2 values were less than 5.5 kPa (41 mmHg). Occasional
      episodes of arrhythmia were seen in Group 1. However, no major adverse effects
      were observed in any of the groups. CONCLUSIONS: In view of the high PETCO2
      levels, spontaneous breathing should be avoided during gynecologic laparoscopy,
      and ventilation to an initial PETCO2 of 4 kPa (30 mmHg) is recommended during
      controlled ventilation.

PMID- 7520258
TI  - Molecular detection and identification of type I interferon mRNAs.
AB  - The development of a technique for identifying murine type I interferon messenger
      RNAs is described that involves the following essential steps: (a) the reverse
      transcription of total RNA extracts using oligo(dT)12-18 as a primer, (b) the
      amplification of any type I interferon cDNAs produced by polymerase chain
      reaction, and (c) the identification of interferon subtypes by hybridization of
      the polymerase chain reaction products to specific oligonucleotides. The
      technique was used to characterize the expression of the mouse interferon
      subtypes alpha 1, alpha 4, alpha 5, alpha 6, and beta in murine L929 cells that
      had been infected with Newcastle disease virus. The data derived from this study
      are in excellent agreement with earlier RNA protection experiments performed in
      the same system to characterize expression of the same genes. The present
      technique has advantages over those used previously, including superior
      sensitivity, speed, and far smaller input RNA requirements. The technique is not
      only applicable to other in vitro systems, but is appropriate for use in vivo.

PMID- 7520259
TI  - An approach to the intramolecular localization of the thiol ester bonds in the
      internal cavity of human alpha 2-macroglobulin based on correspondence analysis.
AB  - The plasma proteinase inhibitor alpha 2-macroglobulin (alpha 2M) can trap small
      proteins including cytokines. With the four internal thiol ester bonds being
      involved in the covalent binding of proteinases and other ligands, it was of
      interest to precisely localize these active groups in the alpha 2M molecule. This
      was approached by comparing methylamine-transformed human alpha 2M (alpha 2M-MA)
      and alpha 2M-MA chemically coupled to cytochrome c (Cyt c). This enzyme was
      chosen because of its size, which is close to that of cytokines, and because of
      the easy quantification of the reaction stoichiometry. The two molecular species
      were first mixed in a single sample that was deposited on a carbon-coated grid,
      negatively stained, and imaged in the electron microscope. The aligned images of
      the two macromolecular species were then separated by correspondence analysis and
      hierarchical ascendant classification and compared through the calculation of a
      subtraction image. The interest of this approach is that prior to the separation
      of the images, the two molecular species are subjected to rigorously identical
      treatments. The subtraction images between the average images of alpha 2M-MA and
      Cyt c-alpha 2M-MA allowed an unambiguous localization of the Cyt c molecules in
      the internal cavity of the alpha 2M molecule. The internal cavity is gradually
      filled when the Cyt c/alpha 2M ratio increases. However, it is not yet clear
      whether the thiol groups are located in the median portion of the wall or in the
      interwall (paddle) structure.

PMID- 7520260
TI  - Effect of recombinant human granulocyte-colony stimulation factor (rhG-CSF) on
      immune system in pediatric patients with aplastic anemia.
AB  - To determine the effect of recombinant human granulocyte-colony stimulation
      factor (rhG-CSF) on the immune system, serum immunoglobulins, lymphocyte subsets,
      and serum cytokines were analyzed in eight pediatric patients with aplastic
      anemia (AA) during 8-week rhG-CSF therapy. The rhG-CSF was administered either
      subcutaneously (200 micrograms/m2 x 4 weeks, followed by 400 micrograms/m2 x 4
      weeks) or intravenously (400 micrograms/m2 x 4 weeks, followed by 800
      micrograms/m2 x 4 weeks). In response to rhG-CSF therapy, neutrophil counts
      exceeded the pretreatment counts by twofold during the first week except for one
      case that did not attain twofold increase until day 41. While serum IgG and IgA
      were not affected, serum IgM was elevated during treatment in six of the eight
      cases to more than 1.2-fold basal levels (P < 0.04); however, there was no
      increase in serum interleukin (IL)-6 and interferon-gamma levels. On the other
      hand, CD56 positive NK cells significantly dropped from 7.7% to 4.5% (P < 0.02).
      These results indicate that systemic administration of rhG-CSF affects not only
      the neutrophil count, but also serum IgM levels and the natural killer cell
      population in patients with AA.

PMID- 7520261
TI  - Enhancement of hybridization efficiency in interphase cytogenetics on paraffin
      embedded tissue sections by microwave treatment.
AB  - To enhance the efficiency of in situ hybridization in interphase cytogenetics on
      formalin-fixed and paraffin-embedded tissue sections we studied the effect of
      microwave heating as an addition to tissue pretreatment. The modified protocol
      resulted in a reduction of proteolytic digestion time and of effective enzyme
      concentration. Apart from that, reproducibility was raised and in large sections
      successful hybridization was more homogenous. We conclude, that the given
      technical recommendations should be useful for the study of chromosomal
      aberrations in routinely processed tissues.

PMID- 7520262
TI  - Vascular targeting and the inhibition of angiogenesis.
AB  - Recent advances in our understanding of the process by which tumours elicit an
      angiogenic response, and of differences between normal and tumour vasculature,
      are revealing new strategies for anticancer therapy. The current status of anti
      angiogenic therapy, together with approaches to targeting tumour vasculature, is
      reviewed. In particular, the advantages of using tumour vasculature as a target
      for anticancer gene therapy are outlined.

PMID- 7520263
TI  - 1;17 translocations and other chromosome 17 rearrangements in human primary
      neuroblastoma tumors and cell lines.
AB  - We report on the finding of a t(1;17) in two primary neuroblastomas. Subsequent
      fluorescence in situ hybridization (FISH) analysis revealed the presence of 1;17
      translocations in four out of nine neuroblastoma cell lines. The chromosome 1
      short arm breakpoints were determined using region-specific probes. FISH
      screening also demonstrated or confirmed the presence of 11;17 translocations in
      three cell lines and other chromosome 17 rearrangements in those cell lines that
      did not carry a t(1;17) or t(11;17). Our data extend previous cytogenetic
      findings and suggest that, in addition to the known involvement of chromosome 1,
      one or more genes on chromosome 17 also play a role in neuroblastoma development.

PMID- 7520265
TI  - Deletions on chromosome 22 in sporadic meningioma.
AB  - Meningiomas are the second most common group of primary central nervous system
      tumors in humans. Cytogenetic and molecular studies imply that genes involved in
      the primary development of meningioma reside on chromosome 22. The recently
      characterized neurofibromatosis type 2 gene (NF2) has been shown to be mutated in
      two cases of sporadic meningioma, suggesting that this is the chromosome 22 gene
      which is involved in tumorigenesis. We have investigated a series of 170
      meningiomas by deletion mapping analysis with 43 markers from chromosome 22 to
      ascertain if NF2 is the only gene on this autosome that is inactivated. Half of
      the tumors showed results consistent with monosomy for chromosome 22, whereas 13
      cases showed terminal deletions of 22q, including the NF2 region. Homozygous
      (complete) deletions were detected in tumors from two patients. In one of them
      complete loss was found at the NF2 locus and cosmid contigs from the region were
      used to determine the extent of the deletions. The second tumor showed homozygous
      loss of two large genomic regions outside the NF2 region. These aberrations were
      confined to only one part of this large tumor, suggesting that they may be
      involved in the later stages of meningioma development. An additional four tumors
      had interstitial deletions on chromosome 22, in three of them without overlap
      with NF2. Our results show that NF2 is completely inactivated in sporadic
      meningioma but do not rule out the possibility that additional chromosome 22 loci
      are important in tumorigenesis.

PMID- 7520264
TI  - Non-random chromosome rearrangements in adenoid cystic carcinoma of the salivary
      glands.
AB  - The chromosomal findings in 10 adenoid cystic carcinomas (ACC) of the salivary
      glands are described. Clonal numerical deviations as the sole anomaly were
      detected in four cases and structurally rearranged stemlines and sidelines in
      four cases. An apparently identical t(6;9)(q23;p21) was found in two tumors; in
      one case the translocation was part of the abnormal stemline and in the other
      case it was the sole anomaly in a single variant cell. A similar or identical
      t(6;9)(q21-24;p13-23) has recently been reported in three of 15 previously
      published cases of ACC. The three remaining tumors with abnormal stemlines all
      had rearrangements of chromosome 9, including t(1;9)(q21;p21-22),
      der(9)i(9)(q10)inv(9)(q12q13), and der(X)t(X;9)(p21;p22-23), respectively. The
      latter case also had a t(17;18)(p12;q11.2) that was common to both abnormal
      clones present in this tumor. In addition to other abnormalities, the clone with
      der(X)t(X;9) also showed a del(6)(q13q21). In two cases fluorescence in situ
      hybridization (FISH) was used for further characterization of the marker
      chromosomes. A survey of the present findings together with previous results from
      15 ACC clearly demonstrates that rearrangements of 6q21-24 (deletions or
      translocations in 11 cases), 9p13-23 (translocations in seven cases), and 17p12
      13 (translocations in three cases) are recurrent, and often primary, in ACC, and
      that the t(6;9)(q21-24;p13-23), found in five tumors, is a non-random, primary
      aberration.

PMID- 7520266
TI  - Some desmoid tumors are characterized by trisomy 8.
AB  - Ten desmoid tumors were examined by chromosome banding analysis and by in situ
      hybridization on short-term cultures and frozen sections. Trisomy 8 was detected
      in four out of ten tumors, of which only one had shown trisomy 8 by karyotype
      analysis. Since trisomy 8 has been reported in superficial fibromatoses, which
      are clinically distinct but histologically similar to desmoid tumors, the
      occurrence of trisomy 8 in both may be a further indication of a close
      relationship.

PMID- 7520268
TI  - Identification of a subclass of double minute chromosomes containing centromere
      associated DNA.
AB  - In a study of abnormal chromosomes in non-Hodgkin's lymphoma (NHL) cells we have
      identified one case which contained extrachromosomal chromatin bodies that, on
      the basis of their morphology and negative C-banding, appeared to be double
      minute chromosomes (dmin). However, fluorescence in-situ hybridization (FISH)
      analysis using an X-specific centromeric alphoid repeat probe and a pan
      centromere probe, clearly demonstrated the presence of centromere-associated DNA
      in these dmin. FISH analysis with the pan-centromere probe of the dmin in
      neuroblastoma and sarcoma cells failed to reveal the presence of centromere
      associated DNA, but analysis of two cases of acute myeloid leukemia cells
      revealed centromere-associated DNA in 25% of their dmin. These data indicate the
      existence of dmin that contain centromere-associated DNA and suggest that such
      dmin might represent a new class of extrachromosomal chromatin bodies.

PMID- 7520267
TI  - No TP53 mutations in neuroblastomas detected by PCR-SSCP analysis.
AB  - We have analysed 29 neuroblastomas for TP53 mutations in exons 5 to 8 by means of
      the polymerase chain reaction in combination with the single-strand conformation
      polymorphism technique. We could not detect any mutation. These results indicate
      that, in contrast to the majority of tumors so far studied, TP53 mutations do not
      seem to be important for the development of neuroblastomas.

PMID- 7520269
TI  - TP53 alterations and clinical outcome in low grade astrocytomas.
AB  - Thirty-eight WHO grade II astrocytomas and 10 malignant recurrent gliomas in
      these patients were examined for the presence of TP53 alterations. Seventeen/38
      low grade astrocytomas and 6/10 malignant recurrent tumors harbored mutations of
      the gene detected by SSCP analysis and direct sequencing of PCR products. TP53
      mutations in five out of six high grade mutant tumors were already present in the
      corresponding low grade astrocytomas. In two cases, TP53 mutations present in the
      low grade astrocytoma could not be demonstrated in the recurrent glioma.
      Immunohistochemistry with two different antibodies to the human TP53 protein
      revealed nuclear immunoreaction of tumor cells in 11/38 low grade and in 8/10
      recurrent tumors. There was no correlation between the presence of TP53
      alteration and clinical course. We conclude that, although TP53 mutations are
      detectable in a substantial fraction of WHO grade II astrocytomas, they do not
      appear to play a role in the malignant progression of these tumors and they are
      not of prognostic significance.

PMID- 7520270
TI  - Induction of senescence and control of tumorigenicity in BK virus transformed
      mouse cells by human chromosome 6.
AB  - Viral transformation models may be useful to detect and map human tumor
      suppressor genes. BK virus (BKV), a human papovavirus, readily transforms rodent
      cells but is unable to transform human cells, suggesting that oncosuppressive
      functions expressed in human cells control BKV oncogenic activity. We have
      transferred human chromosome 6 to BKV-transformed mouse pRPcT1ss1 cells. The
      great majority of the colonies growing in selective medium degenerated by
      senescence. Only five hybrid pRPcT1ss1/H6 clones maintained the immortalized
      phenotype of the recipient cell line. All the immortalized clones had two common
      regions of deletion involving bands 6q21-22 and the SOD2 gene in 6q25. Senescent
      colonies carried an intact chromosome 6. A specific human sequence in 6q21-22 was
      amplified by PCR in senescent cells, suggesting that this region harbors a gene
      inducing senescence. The SOD2 deletion confirms recent data on the role of the Mn
      dependent superoxide dismutase in inhibition of proliferation. The
      monochromosomic hybrids bearing a deleted chromosome 6 showed a reverted
      phenotype in vitro and a significantly longer latency period before they were
      tumorigenic in nude mice, indicating the presence of a tumor suppressor gene in
      the residual regions of chromosome 6. Molecular mapping suggests that this gene
      is located in 6q27. The BKV transformation model detects genes inducing
      senescence and tumor suppressor genes on human chromosome 6 and may represent a
      useful system to isolate and clone such genes.

PMID- 7520272
TI  - Cell lineage involvement of recurrent chromosomal abnormalities in hematologic
      neoplasms.
AB  - Analysis of most hematologic neoplasms indicates the involvement of one or more
      cell lineages in the bone marrow and/or the blood but rules out the involvement
      of all lineages in any one neoplasm. It is important to detect lineage
      involvement in order to clarify which stem cells are involved in leukemia, to
      predict prognosis, and to select appropriate treatment. Our aim was to study the
      cell lineage involvement of some of the recurrent chromosomal abnormalities seen
      in hematological neoplasms. The direct morphology-antibody-chromosomes (MAC)
      method was used. The deletion 20q in myeloproliferative diseases (MPD), the
      deletion of 5q and t(1;7) in myelodysplastic syndromes (MDS), and t(3;3) in acute
      myeloid leukemia subtype M7 (AML-M7) were seen in all or at least in two myeloid
      lineages. These were interpreted as stem cell abnormalities. Deletion 13q in MPD,
      t(8;21) in AML-M2 and t(15;17) in AML-M3 were seen in granulocytic lineages only;
      t(14;18) in non-Hodgkin's lymphoma and trisomy 12 as the sole abnormality in
      chronic lymphocytic leukemia (B-CLL) were seen only in immunoglobulin light chain
      clonal B cells; inversion 14 in T-CLL was seen only in T cells, whereas t(15;14)
      in acute lymphocytic leukemia with eosinophilia (ALL-EO) was seen in lymphoid
      stem cells but not in mature granulocytes or lymphocytes. Additional
      abnormalities (in addition to the Philadelphia chromosome) in chronic myeloid
      leukemia (CML) were seen in all myeloid cell lineages and also in mature
      granulocytes, B cells, and large granular lymphocytes. Abnormalities in Hodgkin's
      disease were restricted to CD30-positive Reed-Sternberg cells. Trisomy 8 and
      monosomy 7 are abnormalities that may be present in either stem cells or any of
      the single cell lineages.

PMID- 7520271
TI  - Complex composition and co-amplification of SAS and MDM2 in ring and giant rod
      marker chromosomes in well-differentiated liposarcoma.
AB  - Extra abnormal chromosomes (rings and giant rods) containing chromosome 12
      sequences are characteristic of well-differentiated liposarcoma (WDLPS). By whole
      chromosome painting we found in 6 WDLPS that minimally 5 chromosomes had
      contributed to the formation of the extra abnormal chromosomes. To the constant
      chromosome 12 contribution, sequences were variably added from chromosomes 1, 4,
      and 16. Material from chromosomes 1, 4, and 12 was identified by painting in
      interphase nuclear projections ("blebs") and in micronuclei consistent with the
      concept that blebs are precursors to micronuclei. The complexity of the
      mechanisms generating the extra abnormal chromosomes in WDLPS was also attested
      to by the diversity and, in some cases, intricacy of the patterns of
      fluorescence. To begin to fathom the function of the extra abnormal chromosomes
      we examined the amplification of genes, including SAS, MDM2, and GADD153/CHOP,
      known to be in the region 12q13-14. SAS and MDM2 demonstrated constant co
      amplification. GADD153/CHOP, which is critically rearranged in myxoid
      liposarcoma, was not amplified in WDLPS.

PMID- 7520273
TI  - Demonstration of sweat allergy in cholinergic urticaria.
AB  - Twenty patients with cholinergic urticaria, 11 sex- and age-unmatched patients
      with acute or chronic urticaria and 20 sex- and age-matched non-atopic control
      subjects were skin tested with autologous sweat. All cholinergic urticaria
      patients showed positive immediate-type skin reactions at 2(0)-2(9) dilutions of
      sweat (geometric mean of maximal positive dilutions +/- S.D. was 2(4.6 +/- 2.6),
      while in acute and chronic urticaria only three patients showed positive
      reactions at low dilutions (two 2(0) and one 2(1)) and none of 20 controls showed
      positive reactions. Prausnitz-Kustner (P-K) tests performed with the serum and
      sweat from six patients were all positive at 2(3)-2(8) dilutions. Percent
      histamine release from peripheral leukocytes of five patients challenged with the
      standard sweat samples was significantly higher than in five control subjects.
      Histamine release from leukocytes of the patient on sweat challenging was
      abandoned by acid treatment of leukocytes. Leukocytes, from a healthy subject
      sensitized with the patient's serum, released histamine on sweat challenging.
      These results seem to indicate that cholinergic urticaria patients have a type I
      allergy to their own sweat.

PMID- 7520274
TI  - Early vitrectomy for progressive diabetic proliferations covering the macula.
AB  - The clinical course in 50 eyes was analysed after pars plana vitrectomy for
      progressive diabetic fibrovascular proliferations. Patients were assigned to pars
      plana vitrectomy if progression of proliferations occurred despite a
      photocoagulation treatment with a mean number of 3500 burns and additional
      peripheral cryoablation. All cases had visual impairment because of fibrovascular
      tissue covering the macula without detachment of the macula. Flat proliferations
      were present in all eyes without retinal elevation, vitreous detachment, or
      vitreous haemorrhage. The follow up intervals ranged from 13 months to 39 months
      (mean interval 24 months). Twelve months postoperatively, 36 eyes (72%) showed
      improved visual acuity, five eyes (10%) were worse, and nine eyes (18%) were
      unchanged. Thirty two eyes (64%) achieved a final visual acuity of 0.2 or better,
      and 45 eyes (90%) gained 0.05 or better. In only two eyes could reproliferation
      be observed. The postoperative course indicates that pars plana vitrectomy for
      diabetic fibrovascular proliferations covering the macula can preserve socially
      useful visual acuity of at least 0.05 in most cases.

PMID- 7520275
TI  - Visual function and course of basal laminar drusen combined with vitelliform
      macular detachment.
AB  - Basal laminar drusen (BLD) are small round yellow drusen that are more easily
      visualised angiographically than biomicroscopically, with a 'stars in the sky'
      pattern. Patients with BLD are predisposed to macular vitelliform detachment.
      Little is known about the course of the disease, but the prognosis for retention
      of useful central vision for patients with BLD is thought to be better than for
      patients with typical drusen. A retrospective analysis of clinical and
      angiographic charts of 19 patients with BLD combined with a vitelliform macular
      detachment was performed to precisely describe their course. In addition, nine
      patients were re-examined to allow an analysis of their visual function--that is,
      central visual field, contrast sensitivity, and colour vision. Eyes without
      choroidal new vessels retained a fair visual acuity (mean final visual acuity
      0.5; follow up 4 to 69 months, mean 24 months). In 11 of these eyes visual
      function assessment disclosed a reduction of contrast sensitivity in high and
      medium spatial frequencies in nine eyes (81%), a blue-yellow dyschromatopsia in
      nine eyes (81%), and a mild reduction of foveal threshold in seven eyes (63%).
      Choroidal neovascularisation (CNV) was observed in 12 eyes (31%) with a poor
      final outcome (mean final visual acuity 0.1). Two thirds of cases of CNV were
      observed at the time of presentation; thus this finding may be a bias of a
      referring centre. However, the high prevalence of CNV suggests the need for a
      close follow up of patients with BLD.

PMID- 7520276
TI  - [Ocular manifestations in non-Hodgkin's lymphomas].
AB  - Ocular manifestation in non-Hodgkin lymphomas are rare and they evolute as non
      specific uveitis. The paper presents the case of a 8-year-old boy presenting
      iridic nodular lesion which had appeared in the evolution of a non-Hodgkin
      malignant lymphoma. Various ocular manifestations which may evolute with a non
      Hodgkin malignant lymphoma are also presented.

PMID- 7520278
TI  - Human cell-adhesion molecule CD2 binds CD58 (LFA-3) with a very low affinity and
      an extremely fast dissociation rate but does not bind CD48 or CD59.
AB  - CD2 is a T lymphocyte cell-adhesion molecule (CAM) belonging to the
      immunoglobulin superfamily (IgSF) which mediates transient adhesion of T cells to
      antigen-presenting cells and target cells. Reported ligands for human CD2 include
      the structurally-related IgSF CAMs CD58 (LFA-3) and CD48 as well as, more
      controversially, the unrelated cell-surface glycoprotein CD59. Using surface
      plasmon resonance technology, which avoids several pitfalls of conventional
      binding assays, we recently reported that rat CD2 binds rat CD48 with a very low
      affinity (Kd 60-90 microM) and dissociates rapidly (koff > or = 6 s-1) [van der
      Merwe, P. A., Brown, M. H., Davis, S. J., & Barclay, A. N. (1993) EMBO J. 12,
      4945-4954]. In contrast, a study using conventional equilibrium binding methods
      reported a much higher affinity (Kd 0.4 microM) for human CD2 binding CD58 which
      suggested that the weak binding of rat CD2 to CD48 may not represent a typical
      CAM interaction. In the present study we have used surface plasmon resonance to
      obtain definitive affinity and kinetic data on the interactions of a soluble,
      recombinant form of human CD2 with soluble forms of CD58, CD48, and CD59. Binding
      of CD2 to CD58 was readily detected but we were unable to detect any direct
      interaction between CD2 and either CD59 or CD48 under conditions in which very
      low affinity interactions (Kd approximately 0.5 mM) would have been detected. In
      contrast to previous reports we found that human CD2 bound CD58 with a very low
      affinity (Kd 9-22 microM) and dissociated with an extremely fast dissociation
      rate constant (koff > or = 4 s-1). The association rate constant (kon) could not
      be measured directly but was calculated to be > or = 400,000 M-1s-1. Taken
      together, these results provide conclusive evidence that CAM interactions can
      have very low affinities and extremely fast dissociation rate constants.

PMID- 7520279
TI  - Crystal structures of wild-type p-hydroxybenzoate hydroxylase complexed with 4
      aminobenzoate,2,4-dihydroxybenzoate, and 2-hydroxy-4-aminobenzoate and of the
      Tyr222Ala mutant complexed with 2-hydroxy-4-aminobenzoate. Evidence for a proton
      channel and a new binding mode of the flavin ring.
AB  - The crystal structures of wild-type p-hydroxybenzoate hydroxylase from
      Pseudomonas fluorescens, complexed with the substrate analogues 4-aminobenzoate,
      2,4-dihydroxybenzoate, and 2-hydroxy-4-aminobenzoate have been determined at 2.3
      , 2.5-, and 2.8-A resolution, respectively. In addition, the crystal structure of
      a Tyr222Ala mutant, complexed with 2-hydroxy-4-aminobenzoate, has been determined
      at 2.7-A resolution. The structures have been refined to R factors between 14.5%
      and 15.8% for data between 8.0 A and the high-resolution limit. The differences
      between these complexes and the wild-type enzyme-substrate complex are all
      concentrated in the active site region. Binding of substrate analogues bearing a
      4-amino group (4-aminobenzoate and 2-hydroxy-4-aminobenzoate) leads to binding of
      a water molecule next to the active site Tyr385. As a result, a continuous
      hydrogen-bonding network is present between the 4-amino group of the substrate
      analogue and the side chain of His72. It is likely that this hydrogen-bonding
      network is transiently present during normal catalysis, where it may or may not
      function as a proton channel assisting the deprotonation of the 4-hydroxyl group
      of the normal substrate upon binding to the active site. Binding of substrate
      analogues bearing a hydroxyl group at the 2-position (2,4-dihydroxybenzoate and 2
      hydroxy-4-aminobenzoate) leads to displacement of the flavin ring from the active
      site. The flavin is no longer in the active site (the "in" conformation) but is
      in the cleft leading to the active site instead (the "out" conformation). It is
      proposed that movement of the FAD out of the active site may provide an entrance
      for the substrate to enter the active site and an exit for the product to leave.

PMID- 7520281
TI  - High-level expression and functional reconstitution of Shaker K+ channels.
AB  - Voltage-gated K+ channels were expressed in COS cells transiently transfected
      with a plasmid carrying a cDNA for an inactivation-removed Shaker K+ channel
      driven by an adenovirus promoter. Channel expression was followed by
      immunological detection, binding of radioactive charybdotoxin (CTX), and
      functional reconstitution into planar lipid bilayers. About 10(7) channels per
      transfected cell are expressed on the plasma membrane. The expressed channels are
      glycosylated and competent to bind CTX with the expected characteristics.
      Channels observed after insertion into planar lipid bilayers displayed the
      voltage-dependent gating, conduction, and ion selectivity behavior expected for
      this channel. Channels were solubilized in several detergents without loss of CTX
      binding activity. The results make plausible a systematic attack on the
      purification of milligram-level amounts of functional K+ channels from a
      heterologous expression system.

PMID- 7520283
TI  - Cloning and characterization of cDNAs encoding two normal isoforms of bovine stem
      cell factor.
AB  - The cDNA clones encoding two isoforms of bovine stem cell factor (bSCF) were
      obtained using reverse transcriptase-polymerase chain reaction, and their
      sequences were determined. The deduced amino acid sequences of the longer and
      shorter isoforms of bSCF consist, respectively, of 274 and 246 residues and show
      a high degree of identity to those of SCFs of different animal species. Northern
      blot analysis with the cDNA revealed the expression of a 5.8 kilobase bSCF RNA in
      fetal bovine tissues.

PMID- 7520277
TI  - Interaction of RNA hairpins with the human U1A N-terminal RNA binding domain.
AB  - The isolated 102 amino acid N-terminal RNA binding domain (RBD) of the human U1A
      protein specifically interacts with a short RNA hairpin containing the U1 snRNA
      stem/loop II sequence. This recognition is nucleotide-specific, for substitutions
      of critical nucleotides in the RNA loop decrease binding affinity up to 10(6)
      fold, as measured by nitrocellulose filter binding experiments. The magnitude of
      the loss of binding free energy with single-nucleotide substitution in the
      conserved GCA sequence suggests that the interaction between the RBD and RNA
      occurs through a number of interdependent specific contacts in the complex. 13C
      and 15N NMR experiments, using isotopically-labeled RNA together with unlabeled
      protein, show that the chemical shifts of many protons from the bound RNA are
      substantially different from those of the free RNA, especially in the loop region
      of the hairpin. All these data suggest that there is a conformational change in
      the RNA upon formation of the RBD-RNA complex.

PMID- 7520282
TI  - Protein kinase C activation inhibits cytokine-induced nitric oxide synthesis in
      vascular smooth muscle cells.
AB  - Vascular smooth muscle cells (SMC) respond by relaxation to nitric oxide (NO)
      released from the endothelium which expresses a constitutive, Ca(2+)-dependent NO
      synthase (cNOS). SMC can, however, produce NO themselves upon stimulation by
      proinflammatory cytokines which induce expression of an inducible, Ca(2+)
      independent NO synthase (iNOS). Protein kinase C represents another important
      second messenger system involved in the regulation of SMC contraction. We have
      investigated iNOS expression and NO synthesis in rat vascular SMC treated with
      the cytokines, IFN gamma and TNF alpha, in the presence or absence of the
      activator of protein kinase C, beta-phorbol-12-myristate 13-acetate (PMA).
      Treatment with PMA did not induce any significant accumulation of nitrite, a
      major stable metabolite of NO, in SMC. When added simultaneously with the
      cytokines, PMA significantly reduced nitrite accumulation induced by cytokine
      stimulation in a dose-dependent fashion. This inhibitory effect was mediated by
      activation of PKC since calphostin C, a specific PKC inhibitor, abolished the PMA
      effect. Further analysis of iNOS mRNA with a rat iNOS cDNA probe demonstrated
      that addition of PMA reduced expression of SMC iNOS mRNA, indicating that the
      antagonism in induction of NO synthesis between PMA and the proinflammatory
      cytokines acts on the transcriptional level. The inhibitory effect of PMA may be
      mediated via induction of a suppressor of iNOS expression, since pretreatment
      with PMA reduced NO production after subsequent treatment with cytokines. These
      observations suggest that activation of the PKC pathway is involved in a negative
      regulation of iNOS gene expression and this is compatible with the observation
      that vascular SMC contraction can be induced by PKC activation.

PMID- 7520284
TI  - CD14-dependent induction of protein tyrosine phosphorylation by
      lipopolysaccharide in murine B-lymphoma cells.
AB  - Incubation of the mouse B-lymphoma cell line 70Z/3 with bacterial
      lipopolysaccharide (LPS) results in the secretion of immunoglobulin M (IgM) to
      the cell surface. We now demonstrate that LPS rapidly induces the tyrosine
      phosphorylation of a 41 kDa protein in 70Z/3 cells transfected with CD14, a
      glycosyl phosphatidylinositol-anchored membrane receptor for complexes of LPS and
      LPS binding protein. There was no indication of LPS-mediated tyrosine
      phosphorylation in untransfected 70Z/3 cells, which do not express CD14. The 41
      kDa tyrosine phosphoprotein was specifically induced by LPS, since it was not
      observed after incubation with another activator of IgM expression, interferon
      gamma. Induction of this 41 kDa phosphoprotein was not observed when the
      transfected cells were treated with LPS in the absence of serum. Phosphorylation
      was also blocked by preincubation of the cells with an antibody to CD14.
      Furthermore, lipid A from Rhodobacter sphaeroides inhibited LPS-mediated tyrosine
      phosphorylation and surface IgM expression. Expression of CD14 in the LPS
      unresponsive mutant 70Z/3 cell line 1.3E2 did not result in the secretion of IgM,
      although tyrosine phosphorylation was increased after incubation with LPS,
      suggesting that the mutation in these cells is downstream of the membrane LPS
      receptor.

PMID- 7520286
TI  - Defective CD3 mediated proliferation and LPS responsiveness in multiple
      sclerosis.
AB  - Multiple sclerosis [MS] is a chronic inflammatory disease of the central nervous
      system which has been postulated to be a T cell mediated disease. We examined
      proliferation of mononuclear cells to OKT3 mAb, Con A, ionomycin plus PMA and
      human myelin basic protein in subjects with relapsing-remitting and chronic
      progressive multiple sclerosis. Age and sex matched controls demonstrated a good
      proliferation to anti-CD3 mAb whereas subjects with relapsing-remitting multiple
      sclerosis showed a significantly decreased anti-CD3 mAb response. There was no
      difference in mitogen, ionomycin plus PMA or human MBP proliferation between
      controls and MS subjects. There was also a trend for decreasing anti-CD3 mAb
      proliferation in patients with chronic progressive multiple sclerosis compared to
      controls. LPS significantly decreased anti-CD3 mAb proliferation in controls but
      not in the MS subjects. An abnormality of signal transduction via the CD3 T-cell
      receptor complex in T cells and responsiveness to the immunomodulatory effect of
      IFN inducers may exist in multiple sclerosis.

PMID- 7520280
TI  - Aluminum fluoride activation of bovine transducin induces two distinct
      conformational changes in the alpha subunit.
AB  - We have used resonance energy transfer to read out the interactions of the alpha
      subunit of transducin (alpha T) with the transducin beta gamma subunit complex
      (beta gamma T) and to compare the rate of aluminum fluoride-induced alpha T
      activation, as reflected by the enhancement of the alpha T tryptophan
      fluorescence, with the rate for the dissociation of holotransducin into its
      component subunits. Specifically, a beta gamma T complex that was labeled with 5
      (iodoacetamido)fluorescein (IAF-beta gamma T) served as a donor for resonance
      energy transfer and an alpha T-GDP species labeled with eosin 5-isothiocyanate
      (EITC-alpha TGDP) served as the acceptor. The quenching of IAF-beta gamma T
      fluorescence emission by the addition of the EITC-alpha TGDP species, due to
      resonance energy transfer between the IAF and EITC moieities, ranged from 10% to
      15%. The association of the transducin subunits was rapid (i.e., within the time
      period of mixing) and dose-dependent, yielding an apparent Kd of approximately
      150 nM for the alpha TGDP/beta gamma T interaction. Unexpectedly, we find that
      the dissociation of IAF-beta gamma T from an aluminum fluoride-activated alpha
      TGDP/IAF-beta gamma T complex occurs prior to the onset of the intrinsic
      fluorescence changes in alpha T that accompany activation of this subunit. Thus,
      there are at least two structural changes in alpha T that result from the
      occupation of the gamma-phosphate position in the nucleotide binding cleft of
      alpha T by aluminum fluoride.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520287
TI  - Prostate cancer in Rochester, Minnesota (USA), from 1935 to 1989: increases in
      incidence related to more complete ascertainment.
AB  - Prostate cancer incidence among White men in the United States climbed steadily
      from 45 per 10(5) person-years (PY) during 1945-54 to 102 per 10(5) PYs in 1988.
      To determine whether this increase might be the result of changing diagnostic
      practices, we examined trends in incidence and method of diagnosis in Rochester,
      Minnesota (US), from 1935 to 1989. We found a parallel increase in Rochester in
      non-autopsy diagnoses from 44 (95 percent confidence interval [CI] = 29-58) cases
      per 10(5) PYs in 1935-44 to 71 (CI = 52-89) cases per 10(5) PYs in 1985-87 which
      was driven by diagnoses prompted by digital rectal examination. There was no
      evidence that an increasing proportion of cases was found as the result of
      procedures to treat the symptoms of benign prostatic hyperplasia. Including
      autopsy diagnoses, incidence was stable over this extended interval and was 77
      per 10(5) PYs (CI = 58-97) in 1935-44 and 72 per 10(5) PYs (CI = 53-91) in 1985
      87. Incidence more than doubled after introduction of diagnostic serum prostate
      specific antigen (PSA) assay and was 179 per 10(5) PYs (CI = 145-214) in 1988-89.
      We conclude that prostate-cancer incidence rates are influenced strongly by
      diagnostic practices and that national increases could reflect, to a large
      extent, more complete and earlier ascertainment rather than more frequent
      disease.

PMID- 7520285
TI  - Recombinant methionyl granulocyte colony-stimulating factor (filgrastim): a new
      dimension in immunotherapy.

PMID- 7520288
TI  - How ATP regulates the CFT regulator.

PMID- 7520290
TI  - Side-chain structure and dynamics at the lipid-protein interface: Val1 of the
      gramicidin A channel.
AB  - High resolution dynamics and structural information has been resolved from 2H
      solid-state NMR spectra of the Val-1 side-chain of the gramicidin channel in a
      lipid bilayer. Both powder pattern lineshapes and spectra from uniformly aligned
      samples of gramicidin in lipid bilayers have been analyzed to achieve a fully
      consistant interpretation of the data. Torsional motions about the C alpha C beta
      axis (chi 1) are shown to be three-state jumps in which the occupancy of the
      states is given by the ratio, 75:15:10 for the chi 1 angles of 184 degrees:304
      degrees:64 degrees. The dominant conformer is also the most common conformation
      observed for valines in well defined protein structures. The distribution of
      conformational substates that represents the chi 1 dynamics appears to be largely
      independent of the lipid phase transition and the hydration of the sample.
      However, there is evidence that the residence time between jumps is dependent on
      the lipid phase transition. Although this time is shown to be approximately 1
      microseconds below the phase transition temperature, it is in the fast exchange
      limit above the transition temperature.

PMID- 7520289
TI  - Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid
      bilayers.
AB  - Proton translocation is important in membrane-mediated processes such as ATP
      dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase
      function. The fundamental mechanism, however, is poorly understood. To test the
      theoretical possibility that bundles of hydrophobic alpha-helices could provide a
      low energy pathway for ion translocation through the lipid bilayer, polyamino
      acids were incorporated into extruded liposomes and planar lipid membranes, and
      proton translocation was measured. Liposomes with incorporated long-chain poly-L
      alanine or poly-L-leucine were found to have proton permeability coefficients 5
      to 7 times greater than control liposomes, whereas short-chain polyamino acids
      had relatively little effect. Potassium permeability was not increased markedly
      by any of the polyamino acids tested. Analytical thin layer chromatography
      measurements of lipid content and a fluorescamine assay for amino acids showed
      that there were approximately 135 polyleucine or 65 polyalanine molecules
      associated with each liposome. Fourier transform infrared spectroscopy indicated
      that a major fraction of the long-chain hydrophobic peptides existed in an alpha
      helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl
      was also used to determine whether proton-conducting channels formed in planar
      lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L
      leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency
      of conductive events compared to that seen in KCl or by the other polyamino acids
      in either solution. This finding correlates well with the liposome observations
      in which these two polyamino acids caused the largest increase in membrane proton
      permeability but had little effect on potassium permeability. Poly-L-leucine was
      considerably more conductive than poly-L-alanine due primarily to larger event
      amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine
      caused two populations of conductive events, one in the 0.1-0.5 pA range, and one
      in the 1.0-5.0 pA range, whereas nearly all events caused by poly-L-alanine were
      in the 0.1-0.5 pA range at an applied voltage of +60 mV. The channel-like
      activity appeared to switch between conductive and nonconductive states, with
      most open-times in the range of 50-200 ms. We conclude that hydrophobic polyamino
      acids produce proton-conducting defects in lipid bilayers that may be used to
      model functional proton channels in biological membranes.

PMID- 7520291
TI  - Noise analysis of ion current through the open and the sugar-induced closed state
      of the LamB channel of Escherichia coli outer membrane: evaluation of the sugar
      binding kinetics to the channel interior.
AB  - LamB, a sugar-specific channel of Escherichia coli outer membrane was
      reconstituted into lipid bilayer membranes and the current noise was investigated
      using fast Fourier transformation. The current noise through the open channels
      had a rather small spectral density, which was a function of the inverse
      frequency up to about 100 Hz. The spectral density of the noise of the open LamB
      channels was a quadratic function of the applied voltage. Its magnitude was not
      correlated to the number of channels in the lipid bilayer membrane. Upon addition
      of sugars to the aqueous phase the current decreased in a dose-dependent manner.
      Simultaneously, the spectral density of the current noise increased drastically,
      which indicated interaction of the sugars with the binding site inside the
      channel. The frequency dependence of the spectral density was of Lorentzian type,
      although the power of its frequency dependence was not identical to -2. Analysis
      of the power density spectra using a previously proposed simple model (Benz, R.,
      A. Schmid, and G. H. Vos-Scheperkeuter. 1987. J. Membr. Biol. 100: 12-29),
      allowed the evaluation of the on- and the off-rate constants for the
      maltopentaose binding to the binding site inside the LamB channels. This means
      also that the maltopentaose flux through the LamB channel could be estimated by
      assuming a simple one-site, two-barrier model for the sugar transport from the
      results of the noise analysis.

PMID- 7520292
TI  - Effect of ATP concentration on CFTR Cl- channels: a kinetic analysis of channel
      regulation.
AB  - Phosphorylated cystic fibrosis transmembrane conductance regulator (CFTR) Cl-
      channels require nucleoside triphosphates, such as ATP, to open. As the
      concentration of intracellular ATP increases, the probability of the channel
      being open (Po) increases. To better understand how ATP regulates the channel, we
      studied excised inside-out membrane patches that contained single, phosphorylated
      CFTR Cl- channels and examined the kinetics of gating at different concentrations
      of ATP. As the ATP concentration increased from 0.1 to 3 mM the mean closed time
      decreased, but mean open time did not change. Analysis of the data using
      histograms of open- and closed-state durations, the maximum likelihood method,
      and the log-likelihood ratio test suggested that channel behavior could be
      described by a model containing one open and two closed states (C1<==>C2<==>O).
      ATP regulated phosphorylated channels at the transition between the closed states
      C1 and C2: as the concentration of ATP increased, the rate of transition from C1
      to C2 (C1-->C2) increased. In contrast, transitions from C2 to C1 and between C2
      and the open state (O) were not significantly altered by ATP. Addition of ADP in
      the presence of ATP decreased the transition rate from C1 to C2 without affecting
      other transition rates. These data suggest that ATP regulates CFTR Cl- channels
      through an interaction that increases the rate of transition from the closed
      state to a bursting state in which the channel flickers back and forth between an
      open and a closed state (C2). This transition may reflect ATP binding or perhaps
      a step subsequent to binding.

PMID- 7520293
TI  - The structure of an integral membrane peptide: a deuterium NMR study of
      gramicidin.
AB  - Solid state deuterium NMR was employed on oriented multilamellar dispersions
      consisting of 1,2-dilauryl-sn-glycero-3-phosphatidylcholine and deuterium (2H)
      exchange-labeled gramicidin D, at a lipid to protein molar ratio (L/P) of 15:1,
      in order to study the dynamic structure of the channel conformation of gramicidin
      in a liquid crystalline phase. The corresponding spectra were used to
      discriminate between several structural models for the channel structure of
      gramicidin (based on the left- and right-handed beta 6.3 LD helix) and other
      models based on a structure obtained from high resolution NMR. The oriented
      spectrum is complicated by the fact that many of the doublets, corresponding to
      the 20 exchangeable sites, partially overlap. Furthermore, the asymmetry
      parameter, eta, of the electric field gradient tensor of the amide deuterons is
      large (approximately 0.2) and many of the amide groups are involved in hydrogen
      bonding, which is known to affect the quadrupole coupling constant. In order to
      account for these complications in simulating the spectra in the fast motional
      regime, an ab initio program called Gaussian 90 was employed, which permitted us
      to calculate, by quantum mechanical means, the complete electric field gradient
      tensor for each residue in gramicidin (using two structural models). Our results
      indicated that the left-handed helical models were inconsistent with our observed
      spectra, whereas a model based on the high-resolution structure derived by
      Arseniev and coworkers, but relaxed by a simple energy minimization procedure,
      was consistent with our observed spectra. The molecular order parameter was then
      estimated from the motional narrowing assuming the relaxed (right-handed)
      Arseniev structure. Our resultant order parameter of SZZ = 0.91 translates into
      an rms angle of 14 degrees, formed by the helix axis and the local bilayer
      normal. The strong resemblance between our spectra (and also those reported for
      gramicidin in 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC)
      multilayers) and the spectra of the same peptide incorporated in a lyotropic
      nematic phase, suggests that the lyotropic nematic phase simulates the local
      environment of the lipid bilayer.

PMID- 7520295
TI  - Physiology of beta-endorphins. A close-up view and a review of the literature.
AB  - When an endogenous morphine, beta-endorphin was discovered ten years ago, the
      fact that this morphine is present in the brain and many other tissues suggested
      to neurobiologists that these peptide opiates play a role which goes beyond that
      of a simple modulator of the perception of pain. beta-endorphin is a neurohormone
      which is secreted by the pituitary gland and reaches all tissues present in the
      body by diffusion. Many laboratories have investigated variations in serum levels
      of beta-endorphin under widely varying physiological or pathological conditions.
      Many references to these studies in the literature have thus demonstrated that
      beta-endorphins play a role in certain behavioural patterns (stress, alcoholism),
      in obesity, diabetes and psychiatric diseases. In fact, the activity of beta
      endorphins would appear to have an interesting role to play and are a promising
      feature in the treatment of cerebral aging; in this field, beta-endorphins act
      not only as neuroregulators of other neurotransmitting substances but also, via
      calcium channels, exert an effect on the walls of cerebral arterioles. In situ,
      the role of beta-endorphins at the ionic channel level has been studied using the
      patch-clamp technique. In 1991, E Neher and B Sakmann received the Nobel Medicine
      and Physiology Prize for this work. beta-endorphin, which may be the "missing
      link" between the neuron and the wall of the arteriole, must be considered as
      being a fundamental neurotransmitter in the same way as well-known substances
      such as noradrenaline, acetylcholine, serotonin, dopamine and the GABAergic
      system are also neurotransmitters.

PMID- 7520296
TI  - Striking similarities between HIV-1 Env protein and the apoptosis mediating cell
      surface antigen Fas. Role in the pathogenesis of AIDS.
AB  - We have designed a computer strategy in order to detect systematically peptidic
      sites with the potential of interfering with the immune regulatory processes.
      Applying this software to HIV-1 proteins has led us to unravel a few peptidic
      sites which could either act directly or be the targets of an auto-immune
      reaction during HIV-1 infection. We previously reported that the SLWDQ
      pentapeptide identity with a critical site of CD4 could trigger in HIV-1 infected
      individuals both an humoral and a cellular autoimmune reaction. In this study, we
      focused on surprising similitudes unravelled by our software Automat, between HIV
      1/2 and another immunoregulatory molecule, the Fas protein which is also called
      the apoptosis-mediating cell-surface antigen.

PMID- 7520294
TI  - Dynamics of an integral membrane peptide: a deuterium NMR relaxation study of
      gramicidin.
AB  - Solid state deuterium (2H) NMR inversion-recovery and Jeener-Broekaert relaxation
      experiments were performed on oriented multilamellar dispersions consisting of
      1,2-dilauroyl-sn-glycero-3-phosphatidylcholine and 2H exchange-labeled gramicidin
      D, at a lipid to protein molar ratio (L/P) of 15:1, in order to study the
      dynamics of the channel conformation of the peptide in a liquid crystalline
      phase. Our dynamic model for the whole body motions of the peptide includes
      diffusion of the peptide around its helix axis and a wobbling diffusion around a
      second axis perpendicular to the local bilayer normal in a simple Maier-Saupe
      mean field potential. This anisotropic diffusion is characterized by the
      correlation times, tau R parallel and tau R perpendicular. Aligning the bilayer
      normal perpendicular to the magnetic field and graphing the relaxation rate,
      1/T1Z, as a function of (1-S2N-2H), where S2N-2H represents the orientational
      order parameter, wer were able to estimate the correlation time, tau R parallel,
      for rotational diffusion. Although in the quadrupolar splitting, which varies as
      (3 cos2 theta D-1), has in general two possible solutions to theta D in the range
      0 < or = theta D < or = 90 degrees, the 1/T1Z vs. (1-S2N-2H) curve can be used to
      determine a single value of theta D in this range. Thus, the 1/T1Z vs. (1-S2N-2H)
      profile can be used both to define the axial diffusion rate and to remove
      potential structural ambiguities in the splittings. The T1Z anisotropy permits us
      to solve for the two correlation times (tau R parallel = 6.8 x 10(-9) s and tau R
      perpendicular = 6 x 10(-6) s). The simulated parameters were corroborated by a
      Jeener-Broekaert experiment where the bilayer normal was parallel to the
      principal magnetic field. At this orientation the ratio, J2(2 omega 0)/J1(omega
      0) was obtained in order to estimate the strength of the restoring potential in a
      model-independent fashion. This measurement yields the rms angle, <theta 2>1/2 (=
      16 +/- 2 degrees at 34 degrees C), formed by the peptide helix axis and the
      average bilayer normal.

PMID- 7520298
TI  - NS 004--an activator of Ca(2+)-dependent K+ channels in cerebellar granule cells.
AB  - The large-conductance Ca(2+)-dependent K+ channels or BK channels in cerebellar
      granule cells were studied by patch-clamp technique, and the effects on channel
      activity of the molecule NS 004 (1-(2-hydroxy-5-chlorophenyl)-5-trifluoromethyl-2
      benzimidazolone) were investigated. The channels had a unit conductance of 187
      pS, were blocked by charybdotoxin and activated by internal Ca2+. NS 004 (10-30
      microM) significantly increased the single channel opening frequency as well as
      the mean open time. In whole-cell recordings the compound shifted the BK current
      voltage relationship by up to 40 mV towards negative membrane potentials. NS 004
      is an efficient BK channel opener, which may represent a novel approach to
      relaxation of neuronal cells expressing this type of K+ channel.

PMID- 7520300
TI  - Inducible microglial nitric oxide synthase: a large membrane pool.
AB  - Microglia are the only immunocompetent cells resident in the central nervous
      system which are capable of protecting the brain from infection and tumors. These
      resident macrophages possess a vast array of mechanisms for the destruction of
      bacteria and tumor cells. One of these mechanisms involves the generation of
      nitric oxide which can kill cells by inhibition of glycolysis, the TCA cycle and
      DNA synthesis. In this regard, we demonstrate, for the first time, that the
      inducible form of nitric oxide synthase (NOS) in microglia involves both
      cytosolic and membrane bound pools. Both pools of NOS were potently and stereo
      specifically inhibited by NOS inhibitors. In addition, while these pools were
      unaffected by Ca2+, they were partially inhibited by calmodulin antagonists.
      These data would suggest that inducible NOS in lipopolysaccharide (LPS) treated
      microglia, constitutes two major compartments and may involve a novel isoform
      which is membrane associated. With regard to the possible physiological relevance
      for the membrane-bound NOS, we speculate that this presents an efficient means of
      supplying nitric oxide to the extracellular environment where it could gain rapid
      access to tumors and bacteria. This would result in inhibition of cellular
      function in these invading cells while limiting access of nitric oxide to the
      intracellular environment of microglia where NO could lead to depressed
      microglial function.

PMID- 7520297
TI  - Volume loading with hypertonic saline solution: endocrinologic and circulatory
      responses.
AB  - Hypertonic saline solution appears to be an attractive method of volume
      expansion. In 45 patients undergoing elective aorto-coronary bypass grafting,
      endocrinologic and circulatory responses to volume loading with hypertonic saline
      solution prepared in low molecular weight (MW) hydroxyethyl starch (HES) solution
      (72 g/L NaCl, HES concentration: 6%; MW: 200,000 D; degree of substitution [DS]:
      0.5) (HS-HES) was compared randomly to patients who had received low molecular
      weight HES solution (LMW-HES). A group of patients without volume loading served
      as a control. Volume was infused to double the low pulmonary capillary wedge
      pressure (PCWP < 5 mmHg) after induction of anesthesia. Plasma levels of atrial
      natriuretic peptide (ANP), endothelin, vasopressin, and catecholamines were
      measured before, during, and after cardiopulmonary bypass (CPB) until the first
      postoperative day. In addition to systemic circulatory changes, capillary skin
      blood flow was measured by laser Doppler flowmetry. ANP plasma concentration
      increased in both volume groups (HS-HES: +79%; HES: +32%), whereas it decreased
      in the control (-20%). Infusion of HS-HES resulted in an increase in plasma
      endothelin concentration before and after CPB (from 3 to 6 pg/mL). Five hours
      after CPB, both treatment groups had higher endothelin plasma concentrations than
      the control patients (P < 0.05). Epinephrine and norepinephrine plasma levels
      increased most markedly in the control patients and were highest in the
      postbypass period in these patients. CI increased most after infusion of HS-HES
      (+65%) (P < 0.05). In the postbypass period, CI remained significantly higher in
      both volume groups than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520299
TI  - AMPA receptors have an equal role in spinal nociceptive and non-nociceptive
      transmission.
AB  - The relative roles of receptors for AMPA (alpha-amino-3-hydroxy-5-methylisoxazole
      4-propionic acid) in spinal nociceptive and non-nociceptive transmission were
      studied on dorsal horn wide dynamic range neurones in alpha-chloralose
      anaesthetized spinalized rats. The effects of systemically administered
      competitive and non-competitive AMPA antagonists (the quinoxalinedione NBQX and
      the 2,3-benzodiazepine GYKI 53655) were examined on responses to peripheral
      noxious heat and non-noxious tap stimuli as well as to iontophoretic AMPA and N
      methyl-D-aspartate (NMDA). Both NBQX and GYKI 53655 dose-dependently reduced
      responses to peripheral stimuli and to AMPA. GYKI 53655, the more selective
      antagonist of AMPA vs NMDA, decreased heat and tap responses to the same extent.
      The results indicate that AMPA receptors play a significant and equal, but not
      exclusive, role in mediating nociceptive and non-nociceptive spinal transmission.

PMID- 7520302
TI  - Oncogenes in the study of endothelial cell growth and differentiation.
AB  - During embryogenesis endothelial cells differentiate from mesodermal blood
      islands, proliferate and form new blood vessels throughout embryonic and early
      postnatal life by the processes of vasculogenesis and angiogenesis. Proliferation
      then ceases and is very low in the adult, although it resumes under certain
      physiological and pathological conditions, such as wound healing, tumor growth
      and hemangiomatous diseases. Expression of the polyoma middle T (PymT) oncogene
      in mouse endothelial cells leads to their rapid transformation and to the
      development of hemangiomas. These endothelial tumors allow the establishment of
      endothelioma (End) cell lines, which resemble normal endothelial cells yet
      exhibit a drastically altered proteolytic activity. The specific effects of PymT
      on the growth of endothelial cells appear in part to be mediated through the
      activation of cellular tyrosine kinases.

PMID- 7520303
TI  - Combination of cobalt labelling with immunocytochemical reactions for electron
      microscopic investigations on frog spinal cord.
AB  - Cobalt staining of primary afferents in frog spinal cord was combined with
      peroxidase-antiperoxidase pre-embedding or immunogold post-embedding
      immunocytochemical labelling. Our results have shown that cobalt labelling can
      easily be distinguished from both of the immunoreaction end products. The
      protocol of cobalt labelling did not affect the immunoreactivity of structures.
      The morphology and synaptology of cobalt labelled and immunostained profiles in
      our sections were very similar to those reported in previous studies using
      different double labelling techniques. These results indicate that this new
      combined method could be used as an alternative double labelling technique in
      electron microscopic studies on nervous tissues.

PMID- 7520305
TI  - Role of changes in the vascular endothelium in chronic inflammation.
AB  - The recruitment and activation of lymphoid effector cells into grafted tissue is
      central to the chronic rejection process. The endothelial cells lining inflamed
      vessels appear to be important in initiating and perpetuating these events
      through their expression of adhesion proteins for circulating leukocytes, as well
      as through their production of cytokines and chemokines to attract leukocytes
      into the inflamed tissues and to activate effector functions. Described here is
      our current understanding of the role of the vascular endothelium in leukocyte
      recruitment into inflamed tissues. A model of leukocyte-endothelial cell
      interactions is outlined.

PMID- 7520306
TI  - The pathogenesis of coronary arteriosclerosis ("chronic rejection") in
      transplanted hearts.
AB  - "Chronic rejection" of allografts may mean different things to different people.
      Some use this term to refer to a process more specifically described as
      arteriosclerotic obstruction of the coronary arteries of transplanted hearts. A
      number of mechanisms might contribute to the pathogenesis of this accelerated
      form of arterial disease, including administration of immunosuppressive agents
      such as corticosteroids with attendant hyperlipoproteinemia, viral infections, or
      ischemic injury of coronary artery endothelium occurring between harvest and
      reimplantation. However, involvement of the engrafted vessels with sparing of the
      host's native arteries suggested to us that immune phenomena underlie graft
      arteriosclerosis. In 1989 we proposed a model for the pathogenesis of accelerated
      arteriosclerosis associated with cardiac transplantation that linked a cellular
      immune response akin to delayed-type hypersensitivity to leukocyte recruitment
      and altered vascular cell function via a cytokine cascade (1). In support of this
      concept, coronary artery endothelium can express class II histocompatibility
      antigens (HLA) that might elicit a cellular immune response (2, 3). Leukocytes
      including macrophages and T lymphocytes accumulate in transplanted coronary
      arteries, as would be expected if an ongoing immune or inflammatory response
      contributed to this type of "chronic rejection". As we have previously suggested,
      T cells activated by graft endothelial cells that bear class II HLA probably
      secrete cytokines that could promote macrophage recruitment and activation, and
      proliferation and extracellular matrix synthesis by smooth muscle cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7520304
TI  - Endothelial activation and chronic allograft rejection.
AB  - Microvascular endothelial cells are actively involved in acute and hyperacute
      allograft rejection. In acute rejection, inflamed graft endothelia increase their
      expression of cell adhesion and antigen-presentation molecules, thereby
      initiating and promoting various mechanisms of cellular immune rejection. In
      hyperacute rejection, preformed antibodies bind to graft endothelial cells and
      initiate endothelial procoagulant activity. These disparate immune responses
      appear to reflect different manifestations of endothelial cell activation. We
      hypothesize that chronic allograft rejection is a third manifestation of local
      endothelial activation. Chronic rejection is associated with interstitial and/or
      vascular hypertrophy. It is intriguing that among the products of activated
      endothelial cells are extracellular matrix components and growth factors that
      promote tissue reconstruction. This suggests that chronic or repetitive
      stimulation of endothelial cells may cause persistent or periodic release of
      these growth factors, eventually leading to the histopathology of chronic
      rejection. Chronic endothelial stimulation could be accomplished by drugs,
      alloantibodies, immune mediators, or some combination thereof. This leads to the
      question: Do different patterns of endothelial stimulation result in different
      manifestations of endothelial activation? Our studies of acute rejection
      mechanisms in murine cardiac allografts demonstrated that several stable
      endothelial phenotypes can develop during graft inflammation, depending on the
      availability of local immune stimuli (Transplantation 1993: 55: 315). Unpublished
      studies suggest that the steroids prednisolone and dexamethasone can synergize in
      vitro with suboptimal concentrations of interferon-gamma (IFN-gamma) to promote
      the activation of human endothelial cell lines, as manifested by enhanced
      expression of MHC class II but not ICAM-1. These steroids do not influence tumor
      necrosis factor-alpha (TNF-alpha)-induced endothelial behavior.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7520307
TI  - MR imaging of the peripheral nervous system.

PMID- 7520308
TI  - Axonal transport and MR imaging: prospects for contrast agent development.
AB  - Axonal transport plays a critical role in the physiology and pathology of
      neurons, yet there have been virtually no clinical tools for its evaluation in
      human subjects. A wide variety of molecules that can act as axonal transport
      facilitators have been discovered and, in many cases, used to deliver labels
      detectable with histologic methods. Recently a number of investigators have
      reported preliminary success in developing intraneural contrast agents based on
      various versions of dextran-coated magnetite that may render magnetic resonance
      imaging capable of depicting axonal transport. It is not yet clear whether any
      clinically useful agents will eventually be developed, but there has been
      considerable progress in identifying design factors for such a pharmaceutical
      agent.

PMID- 7520301
TI  - Two related low-temperature-inducible genes of Arabidopsis encode proteins
      showing high homology to 14-3-3 proteins, a family of putative kinase regulators.
AB  - We have isolated two Rare Cold-Inducible (RCI1 and RCI2) cDNAs by screening a
      cDNA library prepared from cold-acclimated etiolated seedlings of Arabidopsis
      thaliana with a subtracted probe. RNA-blot hybridizations revealed that the
      expression of both RCI1 and RCI2 genes is induced by low temperature
      independently of the plant organ or the developmental stage considered. However,
      RCI1 mRNA accumulates faster and at higher levels than the RCI2 one indicating
      that these genes have differential responsiveness to cold stress. Additionally,
      when plants are returned to room temperature, RCI1 mRNA decreases faster than
      RCI2. In contrast to most of the cold-inducible plant genes characterized, the
      expression of RCI1 and RCI2 is not induced by ABA or water stress. The nucleotide
      sequences of RCI1 and RCI2 cDNAs predict two acidic polypeptides of 255 and 251
      amino acids with molecular weights of 29 and 28 kDa respectively. The alignment
      of these polypeptides indicates that they have 181 identical amino acids
      suggesting that the corresponding genes have a common origin. Sequence
      comparisons reveal no similarities between the RCI proteins and any other cold
      regulated plant protein so far described. Instead, they demonstrate that the RCI
      proteins are highly homologous to a family of proteins, known as 14-3-3 proteins,
      which are thought to be involved in the regulation of multifunctional protein
      kinases.

PMID- 7520309
TI  - Release of surfactant and a myelin proteolipid apoprotein in spinal tissue by
      decompression.
AB  - Two experiments have been performed on sections of bovine spinal cord, the first
      demonstrating that surface-active phospholipid (SAPL) and myelin proteolipid
      protein (PLP) are released by bubbles produced by decompression. Both
      phospholipid and proteolipid were found to be released in amounts increasing with
      the extent of decompression. The immediate recruitment of surfactant to the
      monolayer coating the pool surface indicated that the SAPL had been "carried" at
      the liquid-air interface of the bubbles. In the second study, electrophoresis was
      used to identify a major portion of the released proteolipid as the PLP much
      studied in recent times for its encephalitogenic properties. These findings are
      offered as a possible explanation for the demyelination often found in pathologic
      studies of divers and for the possible role of SAPL and PLP in stabilizing
      microbubbles/macronuclei during recompression, especially in relation to the
      practice of surface decompression.

PMID- 7520310
TI  - In vitro changes of ganglioside immunostain localization in developing neural
      cells.
AB  - The immunostains of GD3, c-pathway polysialogangliosides and
      gangliotetraosylgangliosides belonging to the a- and b-pathways were analyzed in
      embryo optic lobe cells. Cells were cultured in serum free media with, and
      without, bovine brain ganglioside mixture (largely gangliotetraosylgangliosides).
      Control cells differentiated in vitro, whereas ganglioside treated cells emitted
      almost no neurites. In immature cells, GD3 and c-gangliosides were extensively
      expressed and their immunostains were observed all over the cell (general
      localization), whereas gangliotetraosylgangliosides were scanty and their stain
      was preferentially restricted to discrete areas (in clusters). In control
      differentiated cells, the GD3 expression was strikingly reduced and its
      immunostain appeared in clusters; c-gangliosides were abundant and their stain
      was found with general localization; the expression of
      gangliotetraosylgangliosides became important and their stain was observed with
      general localization in most of the positive cells. In ganglioside treated cells,
      in spite of their undifferentiated morphology, the gangliotetraosylganglioside
      stain appeared with general localization. These results suggest that gangliosides
      involved in neural ontogenesis are preferentially located in clusters when they
      are scarce and have general localization when they are abundant in membranes.

PMID- 7520311
TI  - Discrimination by added ions of ligands at ionotropic excitatory amino acid
      receptors insensitive to N-methyl-D-aspartate in rat brain using membrane binding
      techniques.
AB  - The addition of potassium thiocyanate almost quadrupled binding of [3H]DL-alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) to an AMPA-sensitive
      subclass of brain excitatory amino acid receptors in rat brain synaptic
      membranes, treated with Triton X-100. Among several ligands tested, quisqualic
      acid (QA) was the most potent displacer of [3H]AMPA binding in the absence of
      added SCN- ions, followed by AMPA, 6,7-dinitroquinoxaline-2,3-dione (DNQX), 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX), glutamic (Glu) and kainic (KA) acids
      in a rank order of decreasing potency. The addition of SCN- ions was effective in
      significantly reducing the potencies of antagonists such as DNQX and CNQX,
      without affecting those of agonists including QA, AMPA, Glu and KA. On the other,
      the addition of Ca2+ ions significantly inhibited [3H]KA binding in a
      concentration-dependent manner at concentrations of above 2.5 mM. Calcium ions
      were also effective in significantly potentiating potencies to displace [3H]KA
      binding of antagonists such as DNQX and CNQX, with concomitant reduction of those
      of agonists including KA, QA and Glu. However, N-methyl-D-aspartic acid (NMDA)
      did not affect binding of both radioligands at concentrations of below 0.1 mM.
      These results suggest that both SCN- and Ca2+ ions may be useful to discriminate
      agonists and antagonists among a variety of displacers of ligand binding to the
      non-NMDA receptors in the brain.

PMID- 7520315
TI  - HIV-1-O: a variant of HIV-1.

PMID- 7520316
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7520313
TI  - Serum sensitivity of Burkholderia (Pseudomonas) cepacia isolates from patients
      with cystic fibrosis.
AB  - Bacterial strains which are sensitive to the bactericidal activity of serum are
      generally considered to be less virulent than serum-resistant strains and are
      seldom associated with bacteraemia. Burkholderia (Pseudomonas) cepacia is an
      important pathogen in cystic fibrosis and is associated with rapid fatal
      pulmonary decline and bacteraemia in 20% of colonised patients. In this study 19
      isolates of B. cepacia expressing either rough or smooth LPS were investigated to
      determine the degree of serum sensitivity. Strains expressing rough-LPS were
      serum-sensitive: these included a highly transmissible strain of B. cepacia
      isolated from approximately 50 cystic fibrosis patients attending various U.K.
      regional centres and associated with cases of bacteraemia.

PMID- 7520314
TI  - The alpha/beta-adrenergic receptor blocker arotinolol activates the thermogenesis
      of brown adipose tissue in monosodium-L-glutamate-induced obese mice.
AB  - We have found previously that arotinolol, an alpha/beta-adrenergic blocker,
      increases blood flow in brown adipose tissue (BAT) in a similar extent as BRL
      26830A, a beta 3-adrenoceptor agonist. We tested the hypothesis that arotinolol
      activates thermogenesis in BAT, leading to weight loss in monosodium-L-glutamate
      induced (MSG-induced) obese mice and saline-treated controls. Six weeks of
      standard animal feed (CE-2) containing arotinolol hydrochloride (350 mg/kg CE-2),
      which reduced mean blood pressure in MSG-treated mice, significantly increased
      the mitochondrial protein content in BAT, and activated the specific and total
      binding of guanosine-5'-diphosphate (GDP) in BAT mitochondria, leading to a
      reduction of obesity in both MSG- and saline-treated mice vs. the control groups
      fed with CE-2 diet alone. However, six weeks of CE-2 diet containing propranolol
      hydrochloride (525 mg/kg CE-2) a non-selective beta-blocker, markedly reduced the
      specific and total binding of GDP in BAT mitochondria, leading to weight gain in
      both MSG- and saline-treated mice. These findings support the hypothesis, that
      arotinolol activates BAT thermogenesis, leading to weight loss.

PMID- 7520312
TI  - Modeling studies of the change in conformation required for cleavage of limited
      proteolytic sites.
AB  - Previous analyses of limited proteolytic sites within native, folded protein
      structures have shown that a significant conformational change is required in
      order to facilitate binding into the active site of the attacking proteinase. For
      the serine proteinases, the optimum conformation to match the proteinase binding
      site geometry has been well characterized crystallographically by the conserved
      main-chain geometry of the reactive site loops of their protein inhibitors. A
      good substrate must adopt a conformation very similar to this "target" main-chain
      conformation prior to cleavage. Using a "loop-closure" modeling approach, we have
      tested the ability of a set of tryptic-limited proteolytic sites to achieve this
      target conformation and further tested their suitability for cleavage. The
      results show that in most cases, significant changes in the conformation of at
      least 12 residues are required. All the putative tryptic cleavage sites in 1
      protein, elastase, were also modeled and tested to compare the results to the
      actual nicksite in that protein. These results strongly suggest that large local
      motions proximate to the scissile bond are required for proteolysis, and it is
      this ability to unfold locally without perturbing the overall protein
      conformation that is the prime determinant for limited proteolysis.

PMID- 7520317
TI  - A foodborne outbreak of Shigella sonnei infection in Europe.

PMID- 7520319
TI  - Computer-generated slide technology.
AB  - Presentation technology is available, and it does not have to be expensive. This
      article describes computer hardware and software concepts for graphics use, and
      recommends principles for making cost-effective buying decisions. Also included
      is a previously published technique for making custom computer graphic 35-mm
      slides at minimal expense. This information is vital to anyone lecturing without
      the support of a custom graphics laboratory.

PMID- 7520318
TI  - Effects of alternate-day or daily prednisone treatment on GH and cortisol levels
      in growth-retarded children after renal transplantation.
AB  - Growth retardation after renal transplantation (RTx) is generally attributed to
      prednisone (PDN) administration, although the exact mechanism is poorly
      understood. In a group of 19 growth-retarded patients after RTx, we studied the
      effect of alternate-day (group AD, n = 12) and daily (group D, n = 7) PDN
      treatment on the spontaneous plasma growth hormone (GH) and cortisol profiles,
      for 48 h in group AD and for 24 h in group D. The maximal plasma GH response to
      arginine provocation (ATT) and plasma levels of insulin-like growth factor-1 (IGF
      1), IGF-2 and serum IGF-binding proteins (IGFBP) were also determined. For both
      groups the PDN doses were recalculated as daily doses for comparison. The median
      PDN dose in both groups was similar, 0.15 mg/kg/day, with a range of 0.10-0.25
      mg/kg/day. Glomerular filtration rate (GFR) was above 20 ml/min/1.73 m2 in all
      patients. We hypothesized that alternate-day PDN therapy and even more so daily
      PDN therapy would have a deleterious effect on GH and cortisol secretion and
      would result in lower GH-dependent growth factors as compared to control data of
      healthy children. Our findings revealed that growth-retarded renal allograft
      patients, receiving either alternate-day or daily PDN therapy, have significantly
      lower mean plasma GH levels than controls, but normal diurnal rhythm of GH and
      cortisol secretion as well as normal immunoreactive IGF-1 and -2 levels. Mean
      serum IGFBP-1 levels were normal, but mean serum IGFBP-3 levels were
      significantly increased, while a significant negative correlation was found
      between the GFR and serum IGFBP-3 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520321
TI  - Protective effects of gabexate mesilate on acute pancreatitis induced by
      tacrolimus (FK-506) in rats in which the pancreas was stimulated by caerulein.
AB  - We investigated the acute effects of the immunosuppressive agent, tacrolimus (FK
      506), on the exocrine pancreas, in rats with or without stimulation of the
      pancreas, and evaluated the protective effects exerted by gabexate mesilate
      (FOY). While an intravenous injection of FK-506 did not change serum amylase
      levels during the 5-h observation period, this agent increased pancreatic amylase
      and protein content, and decreased the content of pancreatic DNA. Histologically,
      we observed intra-acinar vacuolization and individual cell necrosis. When the
      pancreas was stimulated by two intraperitoneal injections of caerulein (5
      micrograms/kg) at 1-h intervals, however, which treatment did not induce any
      evident pancreatic change, FK-506 significantly increased serum amylase,
      pancreatic wet weight, and pancreatic amylase and protein, and decreased
      pancreatic DNA. Histologically, there were significant dose-related differences
      in the severity of intra-acinar vacuolization, interstitial edema, neutrophil
      infiltration, individual cell necrosis, and hemorrhage. Levels of intrapancreatic
      elastase were elevated and local pancreatic blood flow was reduced. Treatment
      with FOY improved the FK-506-induced acute pancreatitis, but did not increase the
      pancreatic blood flow. These findings indicate that FK-506 enhances abnormal
      pancreatic enzyme secretion and suggest that therapeutic doses of this agent can
      induce acute pancreatitis when the pancreas is stimulated. A protease inhibitor
      may protect the exocrine pancreas in patients who receive FK-506 after organ
      transplantation.

PMID- 7520323
TI  - High-performance liquid chromatographic determination of 3-hydroxy-3
      methylglutaryl coenzyme A as diphenacyl ester of 3-hydroxy-3-methylglutarate.
AB  - A method for derivatization of (S)-3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) by phenacylation in tetrahexylammonium hydrogensulphate as phase-transfer
      reagent and high-performance liquid chromatography of the HMG-diphenacyl ester is
      described. To avoid interference with buffers and other ions used to dissolve
      biological material, the alkaline hydrolysate of CoA esters has to be neutralized
      with phosphoric rather than hydrochloric acid. The latter reacts with phenacyl
      bromide. The pH during phenacylation has to be maintained in the range 6-7 to
      provide sufficient dissociation of HMG.

PMID- 7520324
TI  - Novel precolumn deproteinization method using a hydroxyapatite cartridge for the
      determination of theophylline and diazepam in human plasma by high-performance
      liquid chromatography with ultraviolet detection.
AB  - The deproteinization of human plasma was carried out using a hydroxy apatite
      cartridge as a precolumn. After human plasma had been passed through the
      cartridge followed by suitable elution, protein-free eluate was obtained within
      only 1 min without the need for centrifugation. Deproteinization was evaluated by
      the determination of albumin, gamma-globulin and transferrin in the eluate by
      high-performance liquid chromatography (HPLC) with UV detection. Determination of
      theophylline and diazepam in human plasma was performed by HPLC with UV
      detection. The proposed method was suitable for the determination of these two
      drugs in human plasma, because it is simple and rapid (retention time of each
      drugs approximately 15 min) and microamounts of sample are required (50-100
      microliters). The calibration graphs for theophylline and diazepam were linear in
      the range 0.1-10 micrograms and 0.1-65 ng, respectively. Recoveries of both drugs
      were over 90% by the standard addition method.

PMID- 7520322
TI  - Anti-ulcer effect of FK 506, immunosuppressive agent, in rats.

PMID- 7520326
TI  - Tumour cell migration in the central nervous system.
AB  - Intrinsic tumours of the central nervous system (CNS) are set apart from solid,
      non-neural primary neoplasms in that, although they seldom metastasize to distant
      organs, they are generally characterised by a diffuse local invasive pattern.
      Indeed, it is this important biological characteristic which precludes successful
      therapeutic intervention in the majority of brain and spinal cord neoplasms.
      While tumours metastasising to the brain are generally well-circumscribed
      lesions, sub-populations of neoplastic cells from intrinsic, neuroectodermal
      tumours may migrate several millimeters away from the brain/tumour interface,
      resulting in a poor demarcation of the neoplasm. These migratory cells give rise
      to recurrent tumours following surgical and adjuvant chemo- and radio-therapeutic
      intervention. The mechanisms which facilitate such migration of neoplastic neural
      cells into the contiguous normal nervous tissue are poorly documented. However,
      migration in this context is likely to be a complex multifaceted phenomenon
      involving cell/cell and cell/extracellular matrix (ECM) adhesion, locomotion,
      angiogenesis and enzymic degradation of the ECM. In particular, cell adhesion
      molecules, ganglioside, paracrine and autocrine growth and motility factors and
      matrix metalloproteinases (MMPs) and their inhibitors probably all play important
      and inter-dependent roles in the migration of neoplastic neural cells.

PMID- 7520320
TI  - Seroepidemiology of hepatitis C virus infection in hemodialysis patients and the
      general population in Fukuoka and Okinawa, Japan.
AB  - In 1992, a seroepidemiologic study was carried out among hemodialysis patients
      and the general population in Fukuoka and Okinawa, Japan to determine the
      presence of hepatitis C virus (HCV) infection and HCV viremia. The markers used
      were antibody to HCV, determined by second-generation assay (anti-HCV), and HCV
      RNA, determined by the polymerase chain reaction. The prevalence of anti-HCV in
      Fukuoka was 3.3%, 73 per 2237 persons, significantly (P < 0.001) higher than the
      0.4%, 5 per 1295, in Okinawa. The prevalence of anti-HCV in hemodialysis patients
      in Fukuoka was 51.9% (161 of 310 patients), significantly (P < 0.001) higher than
      the 9.1% (13 of 143 patients) in Okinawa. The ratio of HCV RNA-positive to anti
      HCV-positive persons was significantly higher in hemodialysis patients (147/174,
      84.5%) than in the general population (49/78, 62.8%) (P < 0.001). Elimination of
      HCV among hemodialysis patients appears to be difficult, as such patients have
      lower immune responses than the general population. In Fukuoka, but not in
      Okinawa, blood used for transfusion was supplied by paid donors at commercial
      blood banks from 1953 to 1969. This may explain why HCV infection is endemic in
      Fukuoka and not in Okinawa. Differences between the prevalence of anti-HCV in the
      hemodialysis patients in Fukuoka and Okinawa reflect differences in the
      prevalence in the general population in these two areas of Japan.

PMID- 7520325
TI  - Capillary zone electrophoresis of two synthetic neuropeptides: examination of
      detectability and resolution as a function of peptide concentration and buffer
      concentration.
AB  - The capillary zone electrophoretic behavior of substance P and methionine
      enkephalin, when the amount of peptide was increased at a constant injection
      volume, was examined using a 50-microns I.D. capillary. Peak-shape distortion
      (asymmetry) increased when the concentration of these two peptides exceeded 1% of
      the buffer concentration. Increasing the buffer concentration increased the peak
      height and decreased the peak width, leading to higher detectability and
      resolution, respectively. Peak area versus analyte concentration remained linear,
      even under the overloading conditions that distorted the peak shape.

PMID- 7520327
TI  - Chemical synthesis of 2',5'-oligoadenylate analogues.

PMID- 7520328
TI  - Oligoadenylate and cyclic AMP: interrelation and mutual regulation.
AB  - The data obtained are in good agreement with the hypothesis that cAMP is involved
      in the control of 2-5A metabolism, including the mediation of the regulation of 2
      5A by IFNs; 2-5A, in turn, affects the intracellular cAMP level. The general
      question originating from the data is that of a biochemical mechanism connecting
      the activation of the cAMP/2-5A system and the effect of depression of cell
      division. In my opinion, this universal effect is the result of the action of the
      known 2-5A-dependent mechanism, namely, RNase L (see review by Pestka et al.
      1987), rather than by any new 2-5A-stimulating enzyme. The RNase L activated by 2
      5A decreases the total level of protein synthesis and accelerates the degradation
      of cellular RNA, resulting in the inhibition of cell growth. It should be
      mentioned that such activation of RNA turnover is generally characteristic for
      nondividing cells, especially for cells in the resting state (Epifanova et al.
      1983). Thus, the regulatory system of cAMP/2-5A is involved evidently in the
      antiproliferative mechanism characteristic for the resting cells, controlling the
      variations in the levels of RNA turnover and protein synthesis.

PMID- 7520329
TI  - Regulation of HIV replication in monocytes by interferon.

PMID- 7520330
TI  - Transmembrane signaling by IFN-alpha.

PMID- 7520331
TI  - Photolabeling of the enzymes of the 2-5A synthetase/RNase L/p68 kinase antiviral
      systems with azido probes.

PMID- 7520333
TI  - Molecular approach to rapid assessment of p53 tumor suppressor mutations in
      esophageal tumors from stained histological slides.
AB  - The analysis of the tumor suppressor gene, p53, is of fundamental importance in
      prognosis and staging in many cancers; however, the molecular techniques required
      to analyze this gene have been expensive, time consuming, and unrelatable to the
      histological appearance of the samples. This research explored one model of
      clinically testing for specific mutations in the p53 gene by scraping selected
      areas of stained histological slides and analyzing for "hot-spot" p53 mutations.
      Selectively removing samples from the stained histological slide will be of
      special value in examining suspicious regions in adenomas, potential metastatic
      regions, and the margins of resected area. A polymerase chain reaction (PCR)
      mediated restriction fragment length polymorphism (RFLP) analysis approach in
      which naturally occurring or primer-mediated mutagenesis-induced restriction
      enzyme sites were utilized to test seven hot-spot mutations. These assays were
      able to detect one mutated sequence in 100, and therefore, were sufficiently
      sensitive to be used with very heterogeneous tumors. Several of the assays could
      be multiplexed to reduce the number of PCRs necessary to screen for the seven
      mutational hot spots. Furthermore, an exact determination of the base change
      could be obtained by direct sequencing of the PCR products. Although this form of
      analysis may be applicable only to certain types of cancers (e.g., bladder,
      brain, colon, esophageal, gastric, thyroid, and ovarian tumors), this approach
      can obtain detailed mutational information from specific regions of a
      histological slide in a cost-effective and timely manner.

PMID- 7520332
TI  - Detection of nuclear retinoic acid receptor mRNA in histological tissue sections
      using nonradioactive in situ hybridization histochemistry.
AB  - Nuclear retinoic acid receptors (RARs) function as ligand-activated trans-acting
      transcription factors and mediate the effects of retinoids on gene expression,
      cell growth, and differentiation. Determination of the receptors' expression in
      premalignant and malignant lesions may provide prognostic value and direct the
      selection of receptor-specific retinoids in cancer prevention or treatment. We
      describe a sensitive and practical in situ hybridization method for the analysis
      of RARs in tissue sections of fixed and embedded surgical specimens. Digoxigenin
      labeled antisense and sense RNA probes were prepared for nuclear RAR-alpha, RAR
      beta, and RAR-gamma. The specificity of the probes for their respective receptor
      mRNAs was demonstrated by Northern blot hybridization to total RNA extracted from
      murine and human cells. Optimal conditions for in situ localization of the RAR
      mRNA were established using cultured tumor cells, and these conditions were then
      used for the detection of RAR mRNA in formalin-fixed, paraffin-embedded sections
      of surgical specimens from human tumors. The hybridization stain was detected in
      the cytoplasm (where it was expected to be localized) and not seen in the cell
      nucleus. This method provides a rapid detection procedure with good resolution
      that allows one to clearly distinguish strongly and weakly stained cells. A
      comparison of receptor expression in head and neck squamous carcinoma specimens
      and in adjacent normal tissues revealed a significant decrease in the level of
      RAR-beta mRNA in the tumor cells.

PMID- 7520335
TI  - Phenotypic stability and variation in cells of the porcine aorta: collagen and
      elastin production.
AB  - The extracellular matrix of the developing vasculature varies in composition as a
      function of time and position. Cellular models of vascular biology and pathology
      depend on the assumption that stable phenotypic characteristics of vascular cells
      can be propagated through several generations of in vitro cultivation. We show
      that the positional and developmental heterogeneity of matrix phenotypes in the
      porcine aorta are expressed by explanted vascular smooth muscle cell (SMC) and
      adventitial cell populations for a limited number of passages. Elastin was
      expressed most highly by thoracic SMC while interstitial collagen production was
      usually maximal in abdominal segments. Parallel gradients of collagen types I,
      III and V, detected by specific ELISA assays, were expressed in early-passage
      SMC. Adventitial cell populations from the abdominal aorta of the neonatal pig
      accumulated significant levels of collagen, while these fibroblasts produced less
      than 10% of the elastin made by SMC. All cell populations expressed alpha-smooth
      muscle actin in vitro. Gradients of collagen and elastin expression were evident
      for no more than three passages, and direct outgrowth of cells without limited
      digestion of the matrix further reduced phenotypic stability. Variation and
      decline of the elastin phenotype could be due to hypermethylation of regulatory
      sequences in the elastin gene or trans-acting factors, but elastin production was
      dose-dependently stimulated to a similar extent (100%; 10 microM 5-azacytidine)
      in all segmental SMC populations at early (p1) and late (p3) passage. These data
      indicated that faithful reflection of in vivo SMC behavior was limited to a few
      population doublings, at least under standard culture conditions. Modification of
      the cellular environment by reducing serum factors, changing matrix, or adding
      mechanical stimulation may increase phenotypic stability.

PMID- 7520336
TI  - Aggrecan in bovine tendon.
AB  - Large proteoglycans were purified by ion-exchange chromatography, gel filtration
      and CsCl gradient centrifugation from the compressed and tensional regions of
      adult bovine deep flexor tendon. Tryptic peptide maps of proteoglycan from the
      compressed region were very similar to maps of aggrecan from bovine articular
      cartilage, with evidence for the presence of all fifteen previously identified
      markers from the G1, G2 and G3 domains. The presence of aggrecan in these samples
      was confirmed by sequencing the G1 peptide YPIHTPR. The equivalent maps for large
      proteoglycan from tensional tendon were also consistent with the presence of
      aggrecan, and this was confirmed by sequencing three marker peptides from each of
      the G2 and G3 domains. However, G1 marker peptides were conspicuously absent from
      tensional samples. Northern blots for aggrecan mRNA showed high levels in cells
      from compressed tendon and articular cartilage. Extended exposure revealed a
      lower level of hybridization to RNA from tensional tendon as well. The results
      confirm that aggrecan, which is similar in core protein structure to articular
      cartilage aggrecan, is the predominant chondroitin sulfate-bearing large
      proteoglycan of compressed tendon. The results also indicate that aggrecan
      fragments lacking the G1 domain can account for the small amounts of chondroitin
      sulfate-bearing large proteoglycan in tensional regions of adult tendon.

PMID- 7520334
TI  - A phase I trial of intravenous interleukin-6 in patients with advanced cancer.
AB  - Eighteen patients were treated with escalating doses of recombinant, Escherichia
      coli-derived human interleukin-6 (IL-6) intravenously every 8 h. Therapy was
      given for two cycles of 7 days each separated by a week off therapy. Fevers and
      chills were observed in most patients. Mild renal and liver function
      abnormalities were noted at higher doses of IL-6. Dose-limiting toxicity was
      reached at 30 micrograms/kg i.v. every 8 h due to reversible neurotoxicity, but
      significant rapidly reversible anemia and hyperglycemia were seen at lower doses.
      Platelet counts, white blood cell counts, and acute phase reactant levels were
      substantially elevated. No antitumor responses were seen. A maximum tolerated
      dose of 10 micrograms/kg i.v. every 8 h for two 7-day cycles is recommended for
      future phase II trials.

PMID- 7520338
TI  - NO as an effector molecule of parasite killing: modulation of its synthesis by
      cytokines.
AB  - It has recently been appreciated that NO, a molecule previously known to play a
      physiologic role in blood pressure regulation, is a major effector molecule of
      macrophage cytotoxicity against a variety of microbial targets, including
      protozoan and helminth parasites. NO production by macrophages is arginine
      dependent and catalyzed by a cytokine-inducible form of the NO synthase. This
      activity is positively controlled by several up-regulatory stimuli (including IFN
      gamma, TNF-alpha, IL-2) and negatively controlled by others (principally IL-10,
      IL-4, TGF-beta). Other cell types, such as endothelial cells and hepatocytes,
      display a similar capacity for NO production in response to cytokine stimulation.
      In murine models of leishmaniasis and schistosomiasis, in vivo NO synthesis
      correlates with protective immunity against infection. The effector molecule that
      plays a similar role in cell-mediated immunity in man has not yet been
      identified.

PMID- 7520337
TI  - Substance P induces inositol 1,4,5-trisphosphate and intracellular free calcium
      increase in cultured normal human epidermal keratinocytes.
AB  - Substance P is a neuropeptide which is present in peripheral C nerve endings and
      released from them. Free nerve endings of C nerve are present in human epidermis.
      The effects of substance P on the transmembrane signaling system of pig epidermal
      sheets were previously reported. In these studies, a small amount of cells other
      than keratinocytes contaminated the epidermal sheets and the species difference
      from human was also noticed. Therefore we investigated the effects of substance P
      on cultured normal human epidermal keratinocytes. Alteration of intracellular
      free calcium (Ca2+) in single living keratinocytes was studied using an inverted
      fluorescence microscope and Ca(2+)-sensitive dye, Fura 2-AM. Treatment of normal
      human epidermal keratinocytes with substance P resulted in an increase in
      inositol 1,4,5-trisphosphate and in intracellular Ca2+. Substance P inhibited DNA
      synthesis of the keratinocytes in a dose-dependent manner. These results are
      consistent with the view that substance P stimulates phosphatidylinositol-4,5
      bisphosphate hydrolysis of human keratinocytes, resulting in inositol 1,4,5
      trisphosphate-Ca2+ signal.

PMID- 7520339
TI  - Serotonin level and turnover rate in brown adipose tissue of developing rats.
AB  - The level and turnover rate (TR) of serotonin (5-HT) were determined in the brown
      adipose tissue (BAT) of rats born and reared at 28 degrees C and 16 degrees C.
      The serotonin/norepinephrine ratio was high in BAT of both groups for the first 2
      days. Thereafter it fell. During the first 3 days, the TR was three times higher
      in 16 degrees C rats than in 28 degrees C rats. A similar difference was observed
      for the 5-HIAA/5-HT ratio during that period. It is concluded that 5-HT may act
      on BAT thermogenesis in cold-exposed pups but its mechanism of action is still
      hypothetical.

PMID- 7520340
TI  - Vascular imaging in children.
AB  - Advances in technology have brought about the wide variety of imaging modalities
      that are presently available. The development of digital subtraction angiography,
      computed tomography, ultrasonography, and magnetic resonance imaging have had a
      particular impact on vascular imaging. These modalities, general principles of
      study selection, and imaging approaches for specific entities are reviewed.

PMID- 7520341
TI  - Effects of a primary immune response to T-cell dependent antigen on serotonin
      metabolism in frontal cortex: in vivo microdialysis study in freely moving
      Fischer 344 rat.
AB  - Antigenic challenge is known to influence brain catecholamine turnover, e.g.
      hypothalamic norepinephrine activity, but little is known about effects on the
      activity of serotoninergic neurons, i.e. the release of the neurotransmitter at
      nerve terminals. In the present study, we first investigated the changes of
      central serotonin (5-HT) metabolism in Fischer 344 male rats at 2, 3, 4 and 5
      days following i.v. immunization with sheep red blood cell (SRBC). Major
      decreases in 5-HT levels were evident in the hypothalamus (Hy) and cortex (Cx) at
      a time which corresponded to the late phase of the production of specific
      antibodies to SRBC measured with a plaque-forming cell assay (PFC). A
      pretreatment with an immunosuppressive drug, cyclosporin A (CsA; 12.5 mg/kg by
      gavage for 7 days) prevented the decreases in cortical 5-HT levels.
      Concomitantly, a 2-fold increase in the basal 5-HT release at frontocortical
      nerve terminals was observed by using in vivo microdialysis in awake rats on Day
      3 following SRBC inoculation. This effect was totally suppressed by CsA. Our data
      suggest that the decrease in brain 5-HT levels that occurs after antigen
      administration may reflect a specific short-lasting CsA-dependent-release of 5-HT
      at frontocortical nerve terminals at a time (Day 3 or 4) when the splenic immune
      response is maximal.

PMID- 7520342
TI  - Nitric oxide participates in excitotoxic mechanisms induced by chemical hypoxia.
AB  - Changes in the activity of the NMDA receptor-gated ionic channels induced by
      potassium cyanide were studied in rat hippocampal slices utilizing a [3H]MK-801
      binding technique. A 30-min exposure of slices to potassium cyanide (KCN)
      increased MK-801 binding by 252%. Co-application of N omega-nitro-L-arginine
      (NNLA), a competitive antagonist of nitric oxide (NO) synthase, reduced this
      increase by 72%. This inhibition by NNLA was completely reversed by an excess of
      L-arginine, a substrate for NO synthase, suggesting that the KCN-induced increase
      in MK-801 binding is mediated by NO synthase activity. KCN had no effect on MK
      801 binding in synaptic membranes. In Ca(2+)-containing medium, KCN increased the
      release of glutamate, aspartate and glycine by 4- to 5-fold, and this was blocked
      by application of NNLA. NNLA inhibition was reversed by an excess of L-arginine,
      indicating that KCN-stimulated release of these amino acids is mediated by NO
      synthase activity. In Ca(2+)-free medium, a KCN-induced increase in MK-801
      binding and in excitatory amino acid release was also observed, however, this
      increase was not influenced by NO-related agents, suggesting that these changes
      were not mediated by NO synthase activation. NNLA given after the end of exposure
      to KCN did not reverse the increase in MK-801 binding. These findings suggest
      that NO is involved in the initial activation of NMDA receptor-gated ionic
      channels and in the enhanced amino acid transmitter release induced by KCN, but
      that KCN can also induce some of these effects by a Ca(2+)- and NO-independent
      mechanism.

PMID- 7520343
TI  - Changes in serotonin level in the hypoglossal nucleus region during carbachol
      induced atonia.
AB  - The excitability of hypoglossal (XII) motoneurons innervating genioglossal
      muscles is markedly suppressed during the rapid-eye-movement (REM) stage of
      sleep. This may contribute to airway obstructions in sleep apnea patients. Based
      on our earlier studies in decerebrate cats using injections of carbachol into the
      pons to induce a REM sleep-like atonia and microinjections of serotonin (5HT)
      into the XII motor nucleus, we hypothesized that a sleep-related withdrawal of
      the serotonergic excitatory input to XII motoneurons may play a major role in
      these processes. To test one aspect of this hypothesis, we inserted microdialysis
      probes into the XII nucleus region of decerebrate, paralyzed, vagotomized and
      artificially ventilated cats. The probes were perfused without or with the
      addition of a 5HT reuptake blocker, clomipramine. The levels of 5HT and its
      metabolite, 5-hydroxyindoleacetic acid (5HIAA), were determined using HPLC and
      electrochemical detection in dialysate samples collected over successive 20 min
      periods under four successive experimental conditions: control (at least 2 h
      after probe insertion); during the postural atonia and respiratory depression
      produced by pontine microinjection of carbachol; recovery from the effects of
      carbachol produced by pontine microinjection of atropine; and, to verify that the
      presence of 5HT in the dialysate was related to the activity of serotonergic
      cells of the brainstem, following administration of 8-OH-DPAT, a 5HT 1A receptor
      agonist known to suppress activity in the serotonergic cells of the raphe system.
      After correcting for recovery rates of individual probes, the mean control 5HT
      level in the extracellular space of the XII nucleus region was 7.9 +/- 4.4 nM
      (S.D.) in eight experiments without reuptake blockers. During the carbachol
      induced depression, it was reduced to 70 +/- 20% of the pre-carbachol level. It
      increased to the original control level 98 +/- 27% after pontine injection of
      atropine. 8-OH-DPAT reduced the 5HT level to 43 +/- 14% of the post-atropine
      level. Changes in the 5HIAA level were not as consistent as for 5HT and did not
      reach statistical significance under any of the experimental conditions. Thus, a
      functionally significant amount of 5HT is present in the extracellular space
      within the XII nucleus region, and its decrement during carbachol-induced, REM
      sleep-like atonia is likely to reflect that occurring during natural REM sleep;
      this may contribute to the decreased tone of upper airway muscles and airway
      patency.

PMID- 7520344
TI  - Monoclonal antibodies against the putative divalent cation-receptor that is
      located on parathyroid cells do not stain isolated rat osteoclasts.
AB  - It has been reported that osteoclastic function is regulated by calcium-induced
      alterations in cytoplasmic free calcium ([Ca2+]i), possibly through a specific
      receptor. We have investigated whether osteoclasts, isolated from neonatal rat
      long bones, possess the divalent cation-receptor that has been demonstrated on
      parathyroid cells. Studies with fura-2 loaded adherent single cells showed that
      an increase in extracellular Ca2+ ([Ca2+]e) from 0.5 mM to 10 mM resulted in an
      increase in [Ca2+]i in isolated rat osteoclasts, from a basal value of 94.7 +/-
      16.2 to 150.6 +/- 22.4 nM (means +/- SEM; n = 14). The shape and time course of
      the [Ca2+]i increase varied considerably from cell to cell. Less than half of the
      cells responded with a rapid transient increase whereas the rest responded with a
      slow increase that reached a plateau within 1-2 minutes. When [Ca2+]e was changed
      back to 0.5 mM, a slow decrease in [Ca2+]i was monitored. Immunohistochemical
      staining with two different monoclonal antibodies, recognizing the putative Ca2+
      receptor on parathyroid cells, did not indicate any staining on freshly isolated
      rat osteoclasts. Thus, our data demonstrate that an increase in [Ca2+]e causes an
      elevation of [Ca2+]i in osteoclasts. This increase is not mediated via the
      putative cation-receptor found on parathyroid cells.

PMID- 7520346
TI  - Comparison of different serum prostate specific antigen measures for early
      prostate cancer detection.

PMID- 7520345
TI  - Alterations in glycosaminoglycan concentration and sulfation during chondrocyte
      maturation.
AB  - We have used antibodies to chondroitin 4- and 6-sulfate and keratan sulfate along
      with Alcian blue staining of sulfated proteoglycans to investigate changes in
      content and sulfation within the avian growth plate. In normal chicks,
      chondroitin 4- and 6-sulfate content were similar in the proliferating and
      transitional zones but in the hypertrophic zone, chondroitin 4- and 6-sulfate
      were slightly lower (13% and 18%, respectively) and keratan sulfate was markedly
      lower (58%). Compared with the proliferative zone, Alcian blue staining of
      sulfated glycosaminoglycans was markedly lower in both the transitional (46%) and
      hypertrophic (22%) zones. In tibial dyschondroplasia, where chondrocyte
      maturation is arrested at the transitional zone, there was no difference in the
      chondroitin 4- and 6-sulfate or keratan sulfate staining between the
      proliferative and transitional zones, which were similar to normal birds. With
      Alcian blue staining there was no difference in the intensity of the staining
      within the proliferating zone compared with normal birds but staining in the
      transitional chondrocytes was markedly higher (39%). These results suggest that
      in the early steps of chondrocyte maturation there may be a decrease in the
      degree of glycosaminoglycan sulfation without any alteration in glycosaminoglycan
      concentration, and that further maturation may be accompanied by a change in the
      nature of the proteoglycans which may also affect the level of sulfation.

PMID- 7520347
TI  - Mechanism of the abnormal vitamin K-dependent gamma-carboxylation process in
      human hepatocellular carcinomas.
AB  - BACKGROUND: An important marker for hepatocellular carcinoma is the presence of
      des-gamma-carboxy (abnormal) prothrombin. However, the molecular basis for the
      reduced carboxylation of prothrombin is unknown. METHODS: Two groups of patients
      were defined according to the absence (Group I, n = 7) or presence (Group II, n =
      8) of des-gamma-carboxy prothrombin. The enzymatic activity of gamma-carboxylase
      and the total microsomal prothrombin concentration were determined in all tumors.
      The kinetic parameters for the synthetic peptide Phe-Leu-Glu-Glu-Leu (FLEEL) were
      measured in eight tumors. The gamma-carboxylase mRNA expression was evaluated by
      Northern blot analysis in 12 of 15 tumors. In addition, the total vitamin K
      content (K1, K1 epoxide, and menaquinones 4-10) in 10 tumors was investigated by
      high performance liquid chromatography. RESULTS: Concentrations of menaquinones 4
      10 were normal in the nontumorous part of the liver but significantly decreased
      (P = 0.02) in all the tumors (Groups I and II). This decrease was more severe in
      Group II (P = 0.02). The tumors in Group I had normal or increased gamma
      carboxylase activity and increased mRNA expression (P < 0.02) as compared with
      their nontumorous counterparts. The tumors in Group II were heterogeneous. Five
      tumors displayed low gamma-carboxylase activity, associated with low mRNA
      expression in two, whereas two others had high gamma-carboxylase activity and
      mRNA expression. The concentration of FLEEL at half-maximal velocity was normal
      in all the tumors examined (Groups I and II), and a relation was found between
      the level of expression of gamma-carboxylase and the maximal velocity for FLEEL
      carboxylation in the tumors in Group II (r = 0.98; P < 0.01). The microsomal
      content of normal prothrombin was within normal limits in all tumors (Groups I
      and II). CONCLUSIONS: Tumor vitamin K content has a critical role in the
      synthesis of des-gamma-carboxy prothrombin. Furthermore, the gamma-carboxylase
      defect, which is observed in some secreting tumors, is the result of the
      defective gene expression of a normal enzyme and not the consequence of the
      presence of a competitive inhibitor. It is possible that a 75% reduction in gamma
      carboxylase gene expression could take a part in the secretion of des-gamma
      carboxy prothrombin, but this mechanism is not predominant.

PMID- 7520348
TI  - An immunohistochemical study of p53 protein in gallbladder and extrahepatic bile
      duct/ampullary carcinomas.
AB  - BACKGROUND: p53 mutations are known to occur frequently in human cancers,
      including gallbladder carcinoma. However, there has been no study of p53
      expression in extrahepatic bile duct/ampullary carcinoma. Furthermore,
      gallbladder carcinoma is associated with cholelithiasis, whereas no such
      association is known for extrahepatic bile duct carcinoma, suggesting that they
      could arise from different pathogenetic mechanisms. METHODS: Twenty-four
      gallbladder carcinomas and 35 extrahepatic bile duct/ampullary carcinomas were
      stained with an anti-human p53 protein monoclonal antibody by the streptavidin
      biotin immunoperoxidase method. Both the extent and intensity of p53 protein
      staining were noted. RESULTS: Ninety-two percent of the gallbladder carcinomas
      stained for p53 protein compared with only 66% of the extrahepatic bile
      duct/ampullary carcinomas. The statistical significance was maintained even when
      the comparison was restricted to strong p53 staining in moderately to poorly
      differentiated adenocarcinomas (P < 0.05). Of the gallbladder carcinomas, poorly
      differentiated adenocarcinomas stained more strongly than well to moderately
      differentiated adenocarcinomas; the converse was true for extrahepatic bile
      duct/ampullary adenocarcinomas. CONCLUSION: The majority of gallbladder and
      extrahepatic bile duct/ampullary carcinomas stain for p53 protein. The incidence
      and pattern of staining is different, however, and supports the contention that
      these could be different tumors with differing etiologies and pathogenetic
      mechanisms.

PMID- 7520349
TI  - Argyrophilic nucleolar organizer region counts predict survival in thymoma.
AB  - BACKGROUND: The prognosis of thymoma is related mainly to the tumor stage. The
      prognostic value of argyrophilic nucleolar organizer regions (AgNORs) has been
      demonstrated in several human neoplasias. Ninety primary thymomas were
      investigated retrospectively to assess whether AgNOR analysis could offer
      additional prognostic information. METHODS: Sections from surgically resected
      thymomas, routinely fixed in formol and embedded in paraffin, were stained with
      the argyrophilic method of Ploton. The mean number of AgNORs in the nuclei of 100
      tumor cells (AgNOR counts) was calculated for each case. The association between
      AgNOR counts and survival was assessed by means of uni- and multivariate survival
      analyses. RESULTS: On univariate analysis, AgNOR counts were associated
      significantly with 5- and 10-year survival rates (95% and 90%, respectively, for
      thymomas with 5.58 or fewer AgNORs per cell, but only 55% and 44%, respectively,
      for tumors with more than 5.58 AgNORs per cell; P < 0.0001). Histologic subtypes
      of the American classification (P = 0.0006) and clinical stage (P < 0.0001) also
      were correlated with prognosis. The multivariate survival analysis showed that
      AgNOR counts (P = 0.001), clinical stage (P < 0.001), and age (P = 0.011) were
      independent prognostic variables. AgNOR counts were associated with histologic
      subtypes in the American (P = 0.0001) and European (P = 0.005) classifications
      and with the clinical stage (P < 0.0001). Moreover, thymoma cells and
      intermingling lymphocytes showed different numbers of AgNORs and patterns of
      AgNOR distribution. CONCLUSIONS: Analysis of argyrophilic nucleolar organizer
      regions provides useful prognostic information for patients with thymomas and
      offers an exact evaluation of the proliferative activity of the neoplastic cells
      even for thymomas with prominent lymphocytic infiltration.

PMID- 7520350
TI  - Midkine and pleiotrophin expression in normal and malignant breast tissue.
AB  - BACKGROUND: Some growth factors may promote tumor growth by affecting tumor
      angiogenesis. The angiogenic growth factor, pleiotrophin, was demonstrated
      previously in human breast carcinoma tissues; however, the pattern of
      pleiotrophin expression in normal breast tissues has not been established.
      METHODS: The expression of pleiotrophin and the related growth factor, midkine,
      was examined by polymerase chain reaction amplification of reverse transcriptase
      copies of RNA transcripts (RT-PCR) from freshly resected normal and malignant
      human breast tissues. Northern blot analysis of midkine expression was performed
      on a limited number of the specimens and on human and canine breast carcinoma
      cell lines. Clinicopathologic variables from the breast cancer patients were
      examined in relation to the growth factor expression patterns. RESULTS: The
      majority of both malignant and normal breast tissues expressed pleiotrophin. In
      contrast, midkine was expressed frequently in the malignant breast tissues but in
      only one of the normal specimens. Northern blot analysis of the breast carcinoma
      cells lines showed that they commonly expressed midkine transcripts. The only
      correlation of the growth factor expression patterns with the other clinical
      variables was the finding that the three midkine-negative breast carcinoma
      specimens also had low estrogen receptor levels. CONCLUSIONS: By this analysis,
      the expression of pleiotrophin was equivalent in both malignant and normal human
      breast tissues. Midkine, on the other hand, exhibited increased expression in the
      breast carcinomas but showed much lower expression in the normal breast tissue.
      Although the cellular source of the midkine expression was not determined by the
      RT-PCR assay, the Northern blot analysis showed that isolated populations of
      breast cancer cells commonly express this growth factor. This is the first
      example of a tissue simultaneously expressing high amounts of both pleiotrophin
      and midkine, a finding of unclear pathophysiologic significance.

PMID- 7520351
TI  - The detection of breast carcinoma micrometastases in axillary lymph nodes by
      means of reverse transcriptase-polymerase chain reaction.
AB  - BACKGROUND: The development of a sensitive method for the detection of breast
      carcinoma micrometastases in axillary lymph nodes is reported. METHODS: The
      method was based on amplification of MUC1 mRNA, which encodes a core protein of
      polymorphic epithelial mucin, by a reverse transcriptase-polymerase chain
      reaction (RT-PCR). Total RNA, which was extracted from a breast carcinoma cell
      line (MCF-7), primary breast carcinomas, and axillary lymph nodes, was subjected
      to analysis of MUC1 mRNA expression by the RT-PCR method. RESULTS: MUC1 mRNA
      expression was detected by RT-PCR in MCF-7 cells and in all 15 primary breast
      carcinomas but not in control lymph nodes taken from patients with benign
      diseases. A serial dilution study revealed that MUC1 RT-PCR was a very sensitive
      method, detecting one MCF-7 cell per 1,000,000 lymph node cells. The detection
      sensitivity of MUC1 RT-PCR method was compared with that of immunohistochemical
      staining of an epithelial marker (polymorphic epithelial mucin). Fifty axillary
      lymph nodes were obtained from 15 patients with primary breast carcinomas, and
      metastasis in each lymph node was investigated by both methods. The
      immunohistochemical method demonstrated metastasis in nine lymph nodes, and MUC1
      mRNA was detected in all of them. Of the 41 lymph nodes that were diagnosed to be
      devoid of metastasis by immunohistochemistry, MUC1 mRNA was expressed by 6 but
      not by the other 35, indicating the presence of micrometastases in these 6 lymph
      nodes that could be detected only by the MUC1 RT-PCR method. CONCLUSIONS: The
      MUC1 RT-PCR method is more sensitive than immunohistochemistry for the detection
      of micrometastases in axillary lymph nodes. This new method would be of practical
      value in selecting the patients at high risk for relapse from those who are
      histologically lymph node negative.

PMID- 7520353
TI  - Inhibition of anthralin-caused skin tumor promotion and interleukin-1 alpha
      production by potent immunosuppressant FK506.
AB  - The effect of FK506, a potent immunosuppressive agent, on 7,12
      dimethylbenz[alpha]anthracene-initiated and anthralin-promoted skin tumor
      formation was examined in CD-1 mice. A topical application of 0.1 mumol FK506 to
      mouse skin 15 min prior to each anthralin treatment markedly inhibited skin tumor
      formation. Anthralin stimulated IL-1 alpha production in primary cultured mouse
      epidermal cells, and the peak IL-1 alpha level was observed at 6 h after the
      stimulation. Anthralin also stimulated IL-1 alpha release into culture medium.
      Both production and release of Il-1 alpha were markedly inhibited by FK506 (0.1
      or 1 microM). FK506 (1 microM) alone neither affected IL-1 alpha production nor
      its release. It may be possible that the inhibition of IL-1 alpha production by
      FK506 is related to its anti-tumor-promoting action.

PMID- 7520352
TI  - Relative sensitivity and specificity of serum prostate specific antigen (PSA)
      level compared with age-referenced PSA, PSA density, and PSA change. Data from
      the American Cancer Society National Prostate Cancer Detection Project.
AB  - BACKGROUND: Different indexes that may enhance the early detection capability of
      prostate specific antigen (PSA) have been proposed. In addition to the indexes
      relating to the normal PSA level, there are data suggesting the usefulness of the
      PSA level relative to prostate gland volume (PSA density), age-referenced PSA
      level, and PSA change. Little research comparing the sensitivity and specificity
      of these measures in the same population has been reported. METHODS: All subjects
      were participants in the American Cancer Society National Prostate Cancer
      Detection Project. Specificity was studied in 2011 men without prostate cancer,
      and sensitivity was determined for 171 men with prostate cancer. RESULTS:
      Prostate specific antigen change showed the highest specificity (96.4%), and PSA
      density the lowest (85.3%). The most sensitive index was PSA density, which was
      positive for 74.7% of the 171 cases of known cancer. A PSA change of more than
      0.75 ng/ml per year was the least sensitive index (54.8%). Sensitivity and
      specificity varied in a narrow range. Improved performance in specificity was
      achieved only with the loss of sensitivity. CONCLUSIONS: None of the alternative
      indexes commonly used in general early detection practice demonstrated particular
      advantage when compared with the normal PSA concentration, defined as no more
      than 4.0 ng/ml.

PMID- 7520354
TI  - Expression of CD44 abnormal transcripts in human gastric carcinomas.
AB  - Twenty gastric carcinoma cases were studied for the detection of CD44 aberrant
      transcripts using a cDNA/PCR/blot-hybridization technique which can detect splice
      variants containing an aberrant exon 11 of the CD44 gene. All the tumor tissues
      as well as their metastatic foci demonstrated overexpression of CD44 splice
      variants of more than 1.0 kbp than corresponding normal gastric mucosas. Six out
      of nine (66.7%) well-differentiated or intestinal type gastric cancers
      overexpressed more than three aberrant transcripts, whereas ten out of eleven
      (90.9%) poorly differentiated or diffuse type cancers overexpressed single or two
      lower molecular weight variants. These results indicate that the detection of
      CD44 transcription variants can serve as a powerful tool for the diagnosis of
      gastric cancer. It is also suggested from the difference in variant expression
      pattern that well-differentiated type and poorly differentiated type gastric
      carcinomas have different genetic pathways.

PMID- 7520355
TI  - Angiogenic activity of the recombinant hst-1 protein.
AB  - The hst-1 transforming gene encodes a protein which belongs to the FGF family of
      growth factors. We showed previously that a human hst-1 protein produced in
      silkworm cells has in vitro mitogenic activity to vascular endothelial cells.
      Here we report effective synthesis of an unfused human hst-1 protein in E. coli
      and a potent in vivo angiogenic activity of this hst-1 protein by two in vivo
      assays for angiogenesis, chick chorioallantoic membrane assay and rat cornea
      assay. The NIH3T3 transformant transfected with the hst-1 gene appeared to
      develop a highly-vascularized tumor on nude mice. These data showed that the hst
      1 protein has an angiogenic activity in vivo as well as in vitro.

PMID- 7520356
TI  - Morphology, growth, and gene expression in five newly isolated murine
      hepatocellular tumor cell lines.
AB  - Five murine hepatocellular tumor cell lines (HepM-1-5) were isolated and grown in
      a synthetic medium added with hormones, growth factors and/or serum. The
      morphology of these lines ranged from a nearly homogeneous epithelial-like shape
      (HepM-2) to a stromal appearance (HepM-1). The remaining lines displayed a mixed
      morphology. For their proliferation all of the cell lines retained a clear
      dependence on the extracellular calcium level and hormonal and/or serum growth
      factors and, rather homogeneously, they did not express the albumin, alpha
      fetoprotein (with the exception of HepM-2 cells), tyrosine aminotransferase, and
      ornithine transcarbamylase genes, whereas they all exhibited discrete levels of
      the ornithine aminotransferase mRNA. Only HepM-3 and HepM-5 lines expressed the
      procollagen type I gene.

PMID- 7520357
TI  - Carcinogen daily dose-dependence of the biological features and development rate
      of hepatocellular carcinomas induced by 3'-methyl-4-dimethylaminoazobenzene in
      the rat.
AB  - Differences in biological features and the rate development of hepatocellular
      carcinomas (HCCs) induced with various daily doses of 3'-methyl-4
      dimethylaminoazobenzene were investigated. Male Donryu rats at 21 days old were
      fed the carcinogen at concentrations ranging from 50 to 600 ppm in the diet
      continuously, or 600 ppm for 3 weeks followed by a dietary promoting regimen of
      500 ppm phenobarbital. Large (> or = 10 mm) HCCs were monitored and the
      histological features and alpha-fetoprotein (AFP) production analysed. High doses
      of the carcinogen predominantly induced HCCs of high grade malignancy with AFP
      production in a short latent period whereas lower doses and the initiation
      promotion protocol were primarily associated with low grade HCCs lacking AFP
      production and developing after long latent periods. Thus the experimental
      results clearly document that biological features of neoplasms, viewed as a
      spectrum, may markedly differ according to the daily dose of the carcinogen
      applied.

PMID- 7520359
TI  - Inhibition of angiogenesis by the matrix metalloprotease inhibitor N-[2R-2
      (hydroxamidocarbonymethyl)-4-methylpentanoyl)]-L-tryptophan methylamide.
AB  - The inhibitor N-[2R-2-(hydroxamidocarbonymethyl)-4-methylpentanoyl)]-L-
      tryptophan methylamide specifically blocks several matrix metalloproteases,
      enzymes which are thought to be involved in angiogenesis. An extract of Walker
      256 carcinoma in Hydron pellets implanted in the corneas of Sprague-Dawley rats
      was used to stimulate angiogenesis from the vessels of the limbus. Angiogenesis
      was graded visually as the distance penetrated into the cornea and the number of
      vessels generated. The vessel area was also measured by image analysis using
      Image 1 software. Continuous i.v. administration of N-[2
      (hydroxamidocarbonymethyl)-4-methylpentanoyl)]- L-tryptophan methylamide at 32
      mg/kg/day (n = 17) via syringe pump reduced vessel number [25.06 +/- 5.9 (SEM)
      compared to 65.33 +/- 9.0] and vessel area (26.14 +/- 3.2 mm2 compared with 40.96
      +/- 4.6 mm2), but not distance penetrated, compared to vehicle-treated control
      eyes after 6 days. These results confirm the suspected role for matrix
      metalloproteases in angiogenesis and suggest that inhibitors of these enzymes may
      be angiostatic agents.

PMID- 7520358
TI  - Selective 8-hydroxyguanine formation in pancreatic DNA due to a single
      intravenous administration of 4-hydroxyaminoquinoline 1-oxide in rats.
AB  - 8-Hydroxyguanine (8-OHG) formation, a possible initiating event, was determined
      in pancreatic and liver DNA and compared with the genesis of acinar cell and
      hepatocyte necrosis in male Wistar rats given a single intravenous administration
      of 4-hydroxyaminoquinoline 1-oxide (4-HAQO). At the non-necrotic but tumorigenic
      dose of 7.0 mg/kg body weight, 8-OHG was selectively generated in pancreatic DNA,
      in the absence of acinar cell necrosis, at the 6 and 24 h time points and
      repaired by the 48 h time point. When rats were exposed to 4-HAQO at a necrotic
      dose of 14.0 mg/kg body weight, 8-OHG was also selectively formed in pancreatic
      DNA with the same time-dependence of generation and repair, while acinar cell
      necrosis became evident at the 24 h time point and progressed thereafter. Whereas
      no hepatocyte necrosis was detected in any rats, 8-OHG values for liver DNA
      merely expressed slight increases only at the 24 and 48 h time points in rats
      given 14.0 mg/kg body weight of 4-HAQO. The present data suggest that formation
      of oxidative DNA damage, assayed by 8-OHG, in pancreatic DNA is independent from
      toxicity and may be involved, along with quinoline adducts, in mutational events
      underlying 4-HAQO-induced rat acinar cell carcinogenesis.

PMID- 7520360
TI  - Suppressive effect of basic fibroblast growth factor on transendothelial
      emigration of CD4(+) T-lymphocyte.
AB  - The effect of basic fibroblast growth factor (b-FGF), one of the commonest
      angiogenic factors in various cancer types, on lymphocyte adhesion and
      transmigration across the endothelial cell monolayer was investigated using human
      umbilical vein-derived endothelial cells (HUVEC) and type I collagen gel. Forty
      eight h exposure of HUVEC with 2 ng/ml b-FGF significantly decreased the basal
      adhesion of lymphocytes to endothelial cells. The decrease ratio is further
      enhanced by the addition of shear stress in this assay system. When HUVEC was
      stimulated for the last 24 h with optimal conditions of recombinant interleukin 1
      beta, the percentages of transmigration as well as adhesion were also decreased
      significantly by the presence of b-FGF. The expression of intercellular adhesion
      molecule 1 and vascular cell adhesion molecule 1 was down-regulated by b-FGF
      exposure in both resting and activated conditions by recombinant interleukin 1
      beta, supposedly the main reason for this phenomenon. The migrating cells across
      b-FGF-stimulated HUVEC contained a markedly lower percentage of CD4(+) T-cells
      than those across non-treated HUVEC, although the 4B4(+)/2H4(+) ratio in CD4(+) T
      cell populations did not differ significantly. These facts suggest that the
      presence of b-FGF in the angiogenic area suppresses lymphocyte emigration,
      especially that of CD4(+) T-cells, and thus causes insufficient helper function
      in local immune response. This effect of b-FGF was possibly one of the critical
      mechanisms by which cancer cells escape from the host immune reactions in the
      angiogenic stage of tumor development.

PMID- 7520361
TI  - Platelet-activating factor mediates an autocrine proliferative loop in the
      endometrial adenocarcinoma cell line HEC-1A.
AB  - We investigated the synthesis and biological effects of platelet-activating
      factor (PAF) in the human endometrial cancer cell line HEC-1A. We found that HEC
      1A cells actively synthesize and release PAF, as demonstrated by both [3H]acetate
      incorporation into PAF and gas chromatography-mass spectrometry studies. HEC-1A
      cells not only synthesize but also respond to PAF. Indeed, in fura-2-loaded
      cells, PAF stimulates [Ca2+]i increase with a median effective concentration of
      5.6 nM. Furthermore, PAF induces a time-dependent expression increase of the
      nuclear protooncogene c-fos with a median effective concentration of 130 nM and
      stimulates DNA synthesis (median effective concentration, 700 nM). All of these
      effects are inhibited by the PAF receptor antagonist L659,989. Radioligand
      binding studies indicated the presence of two populations of PAF receptors with
      affinity constants in the nanomolar and micromolar range. Since the PAF
      antagonist per se inhibits DNA synthesis and cell proliferation, we suggest that
      PAF supports an autocrine growth circuit in HEC-1A cells. On the contrary, in the
      uterine leiomyosarcoma cell line SK-UT-1, which does not express specific binding
      sites for PAF, neither this phospholipid nor its receptor antagonist affect DNA
      synthesis. Our results provide evidence for the existence of an autocrine
      proliferative loop involving PAF in the endometrial cancer cell line HEC-1A.

PMID- 7520362
TI  - Structural organization and neuropeptide distributions in the equine enteric
      nervous system: an immunohistochemical study using whole-mount preparations from
      the small intestine.
AB  - The architecture and neurochemistry of the enteric nervous system was studied by
      use of whole-mount preparations obtained by microdissection of the horse jejunum.
      A myenteric plexus and two plexuses within the submucosa were identified. The
      external submucosal plexus lying in the outermost region of the submucosa had
      both neural and vascular connections with the inner submucosal plexus situated
      closer to the mucosa. Counts of neurones stained for NADH-diaphorase demonstrated
      the wide variation in size, shape and neurone content of individual ganglia in
      both the external and internal submucosal plexuses. The average number of
      cells/ganglion was similar in each plexus (about 25 cells). Immunoreactivities
      for galanin, vasoactive intestinal peptide and neuropeptide Y were observed in
      nerve cell bodies and fibres of each of the plexuses. Immunoreactivity for
      substance P was extensive and strong in nerve fibres of all plexuses but was
      weaker in cell bodies of the submucosal neurones and absent in the cell bodies of
      the myenteric plexus. Comparative quantitative analysis of immunoreactive cell
      populations with total cell numbers (enzyme staining) was indicative of
      neuropeptide colocalization in the external submucosal plexus.

PMID- 7520363
TI  - Nitric oxide synthase in the rat carotid body and carotid sinus.
AB  - The participation of nitric oxide synthase (NOS) in the innervation of the rat
      carotid body and carotid sinus was investigated by means of NADPH-diaphorase
      histochemistry and NOS immunohistochemistry using antisera raised against
      purified neuronal NOS and a synthetic tridecapeptide. NOS was detected in 23% of
      neurons at the periphery of the carotid bodies. Some negative neurons were
      surrounded by NOS-positive terminals. NOS-containing varicose nerve fibres
      innervated the arterial vascular bed and, to a lesser extent, the islands of
      glomus cells. These fibres persisted after transection of the carotid sinus nerve
      and are probably derived from intrinsic neurons. Large NOS-positive axonal
      swellings in the wall of the carotid sinus were absent after transection of the
      sinus nerve, indicating their sensory origin. The results suggest a neuronal
      nitrergic control of blood flow, neuronal activity and chemoreception in the
      carotid body, and an intrinsic role of NO in the process of arterial
      baroreception.

PMID- 7520365
TI  - Nostril capsaicin application as a model of trigeminal primary sensory neuronal
      activation.
AB  - Capsaicin was applied unilaterally to the nostril mucosa of 18 episodic cluster
      headache sufferers in remission. Plasma and saliva levels of substance P (SP),
      calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide
      (VIP) were measured by radioimmunoassay. Increase of salivary SP-LI and CGRP-LI
      as well as of plasma CGRP-LI occurred after capsaicin stimulation. Capsaicin
      induced neurochemical changes in saliva and in plasma were compared to the
      changes observed during cluster headache attacks measured in a separate study.
      The comparative changes in SP, CGRP and VIP characterizing these two conditions
      suggest that trigeminal capsaicin-sensitive sensory neurones are unlikely to play
      any fundamental role in the mechanics of cluster headache.

PMID- 7520364
TI  - Morphological and functional characteristics of peritoneal mast cells from young
      rats.
AB  - To study why neonatal and young rats are resistant to the effects of some
      secretagogues, such as compound 48/80 and 2.5-S nerve growth factor, we examined
      peritoneal mast cells from 14-15-day-old rats (young rats) and compared them to
      peritoneal mast cells from adults. Peritoneal mast cells from young rats contain
      approximately one-tenth of the amount of histamine observed in adult peritoneal
      mast cells. However, both cell populations contained similar low levels of the
      mucosal mast cell-associated protease rat mast cell protease II. Histochemical
      analysis of peritoneal mast cells from young rats using safranin O and berberine
      sulphate suggested that only a portion of the granules of these cells contained
      heparin. At an ultrastructural level the young rat peritoneal mast cell contains
      relatively few granules. The majority of mast cells from young rats have a
      bilobed or indented nucleus which is only rarely observed in adult cells.
      Functionally, the young rat peritoneal mast cell demonstrates a significantly
      reduced histamine release in response to the connective tissue mast cell-specific
      secretagogues compound 48/80 and 2.5-S nerve growth factor. In contrast, the
      percent histamine release in response to the neurotransmitter substance P, which
      degranulates both connective tissue mast cells and intestinal mucosal mast cells,
      was similar in the adult cells and the young rat cells. This study demonstrates
      substantial differences between the young rat and adult peritoneal mast cells
      which may explain the ability of very young animals to withstand large doses of
      certain secretagogues.

PMID- 7520366
TI  - Demonstration of neuropeptide containing nerves and vasomotor responses to
      perivascular peptides in human cerebral arteries.
AB  - A rich supply of nerve fibers containing neuropeptide Y-like (NPY-LI) and
      tyrosine hydroxylase-like immunoreactivity was seen in human cerebral arteries,
      arterioles and veins. Only a sparse supply of vasoactive intestinal polypeptide
      (VIP-LI), substance P (SP-LI), and calcitonin gene-related peptide (CGRP-LI) was
      demonstrated in the walls of human cerebral vessels. In isolated ring segments of
      human cerebral arteries, NPY and noradrenaline caused vasoconstriction but did
      not potentiate each other. VIP, peptide histidine methionine, SP, neurokinin A,
      and CGRP relaxed arteries precontracted by prostaglandin F2 alpha. The degree of
      innervation and the vasomotor responses are discussed in relation to migraine
      pathophysiology.

PMID- 7520367
TI  - High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient
      anti-myelin basic protein T cell receptor transgenic mice.
AB  - We have generated TCR transgenic mice (T/R+) specific for myelin basic protein
      (MBP) and crossed them to RAG-1-deficient mice to obtain mice (T/R-) that have T
      cells expressing the transgenic TCR but no other lymphocytes. Both T/R+ and T/R-
      mice carry, in the lymph nodes and spleen, large numbers of the potentially
      encephalitogenic CD4+ anti-MBP T cells. These cells respond to MBP in vitro but
      show no signs of activation in vivo. Nevertheless, approximately 14% of H-2u T/R+
      and 100% of H-2u T/R- mice developed spontaneous experimental autoimmune
      encephalomyelitis (EAE) within 12 months. These data indicate that EAE can be
      mediated by CD4+ anti-MBP T cells in the absence of any other lymphocytes and
      that nontransgenic lymphocytes that are present in T/R+ but absent in T/R- mice
      have a protective effect. The data also suggest that spontaneous EAE may be
      triggered by an in situ activation of CD4+ anti-MBP cells in the nervous system.

PMID- 7520368
TI  - S. pombe mei2+ encodes an RNA-binding protein essential for premeiotic DNA
      synthesis and meiosis I, which cooperates with a novel RNA species meiRNA.
AB  - The molecular controls over meiosis are poorly understood compared with those
      over mitosis. Here, we show that S. pombe mei2, which is essential for the
      initiation of premeiotic DNA synthesis, encodes an RNA-binding protein. A
      temperature-sensitive mei2 mutant performs premeiotic DNA synthesis but does not
      undergo meiotic divisions, suggesting that Mei2 is required also for meiosis I. A
      novel, polyadenylated RNA species (meiRNA), which suppresses this temperature
      sensitive defect if overexpressed, specifically binds to Mei2 both in vivo and in
      vitro. Cells without meiRNA perform premeiotic DNA synthesis but cannot undergo
      meiosis I. Mutations that apparently block the RNA binding ability of Mei2
      inhibit premeiotic DNA synthesis. Mei2 is thus likely to couple with another RNA
      species to promote premeiotic DNA synthesis.

PMID- 7520370
TI  - Human plague in 1992.

PMID- 7520369
TI  - Therapeutic approaches to cystic fibrosis: memorandum from a joint WHO/ICF(M)A
      meeting.
AB  - Cystic fibrosis is one of the commonest genetic diseases among Caucasians and
      represents an important cause of suffering and death among children and adults.
      In the past two decades marked prolongation of the life of patients with cystic
      fibrosis has been achieved as the result of improved case-finding and an
      extensive regimen of therapies. More recently, a variety of new approaches to
      therapy have been developed or proposed as the result of advances in cell
      physiology and molecular biology. This article summarizes the presentations and
      discussions made at a joint WHO/ICF(M)A (International Cystic Fibrosis
      (Mucoviscidosis) Association) meeting, held in Washington, DC, on 14 October
      1992, and reviews the current status of possible therapies for cystic fibrosis
      and their implications for treatment in various countries of the world.

PMID- 7520371
TI  - Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA
      in cultured neonatal rat cardiomyocytes.
AB  - We examined whether apoptosis occurs in cardiomyocytes by hypoxia in vitro.
      Neonatal rat cardiomyocytes and nonmyocytes were cultured in 95% N2-5% CO2
      atmosphere to produce hypoxic conditions. DNA fragmentation into integer
      multiples of the internucleosomal DNA length was observed in cardiomyocytes as
      early as 12 hours, whereas nonmyocytes did not show fragmentation of DNA up to 72
      hours. DNA fragmentation of cardiomyocytes induced by hypoxia was also confirmed
      by nick-end labeling in situ. Messenger RNA for Fas antigen, a mediator of
      apoptotic cell death, was expressed in both cardiomyocytes and nonmyocytes as
      revealed by Northern blotting and in situ hybridization. In hypoxic condition,
      Fas messenger RNA levels in cardiomyocytes were upregulated by twofold over
      controls, whereas those of nonmyocytes were downregulated. These results indicate
      that cardiomyocyte death by hypoxia can occur via apoptosis and that Fas antigen
      may be associated with the mechanism of this apoptotic process.

PMID- 7520373
TI  - Effects of clonidine on the reflex cardiovascular responses and release of
      substance P during muscle contraction.
AB  - The effects of microdialyzing clonidine into the L-7 dorsal horn on the
      cardiovascular responses, renal sympathetic nerve activity (RSNA), and release of
      substance P (SP) evoked by static contraction of the triceps surae muscle were
      studied using anesthetized cats. A microdialysis probe was inserted into the
      spinal cord ipsilateral to the muscle being contracted or stretched. Contraction,
      evoked by stimulation of the distal ends of the cut L-7 and S-1 ventral roots for
      1 minute, increased mean arterial pressure (MAP), heart rate (HR), and RSNA by 48
      +/- 6 mm Hg, 18 +/- 2 beats per minute, and 66 +/- 5%, respectively. Passive
      stretch of the same muscle for 1 minute also increased MAP, HR, and RSNA by 51 +/
      6 mm Hg, 17 +/- 2 beats per minute, and 50 +/- 3%, respectively. Microdialysis
      of clonidine (380 mumol/L) blunted the contraction-evoked responses: MAP, HR, and
      RSNA increased by 19 +/- 4 mm Hg, 7 +/- 1 beats per minute, and 24 +/- 5%,
      respectively. The increases elicited by passive stretch were also attenuated
      (MAP, 22 +/- 4 mm Hg; HR, 6 +/- 1 beats per minute; and RSNA, 15 +/- 4%). This
      attenuation by clonidine was dose dependent (3.8 mumol/L, 38 mumol/L, 380
      mumol/L, and 3.8 mmol/L). Preadministration of the alpha 2-adrenergic antagonist
      yohimbine (3 mmol/L) blocked the effect of clonidine (380 mumol/L) on the
      cardiovascular and RSNA responses to muscle contraction. Clonidine (380 mumol/L)
      did not alter the release of SP in the dorsal horn during contraction (before
      clonidine, 0.380 +/- 0.018 fmol/100 microL; after clonidine, 0.356 +/- 0.012
      fmol/100 microL).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520372
TI  - Selective dye and ionic permeability of gap junction channels formed by
      connexin45.
AB  - Gap junctions are thought to mediate the direct intercellular coupling of
      adjacent cells by the gating of an aqueous pore permeable to ions and molecules
      of up to 1 kD or 8 to 14 A in diameter. We performed ion-substitution and dye
      transfer experiments to determine the relative Cl-/K+ conductance and dye
      permeability of anionic fluorescein derivatives in chick connexin45 (Cx45)
      channels. We demonstrate that Cx45 forms a 26 +/- 6-picosiemen (pS) channel with
      a maximum detectable Cl- permeability of 0.2 relative to K+ or Cs+. Although
      homogeneous channel conductances were observed in multichannel recordings, the
      open probability estimates were indicative of nonhomogeneous gating behavior and
      occasional cooperativity. A second conductance state of 19 +/- 4 pS begins to
      predominate at higher voltages. Cx45 gap junctions are permeable to 2',7'
      dichlorofluorescein but are not permeable to the more polar 6-carboxyfluorescein
      dye. These observations suggest that the Cx45 pore diameter is approximately 10 A
      and is associated with a fixed negative charge within the junctional channel.

PMID- 7520374
TI  - Isolation and characterization of human antigen-specific B lymphocytes.
AB  - Antigen-specific B cells from the peripheral blood of immunized donors were
      isolated following rosette formation with antigen-coated immunomagnetic beads and
      were phenotypically and functionally characterized. B cells separated with
      tetanus toxin (TT)- or keyhole limpet hemocyanin (KLH)-coated beads produced
      significant amounts of specific IgM and IgG antibodies when they were transformed
      with Epstein-Barr virus or cultured with autologous T cells in the presence of a
      specific antigen. Cells isolated from peripheral blood mononuclear cells (PBMC)
      with TT-coated beads consisted mostly of B cells (88.7% CD20+). B cells detected
      among the rosetting cells were predominantly sIgM+ with low percentages of the
      other isotype-expressing B cells. The mean percentage of TT-specific B cells
      among adult donors was 0.34% of PBMC, and increased to up to 2% following a
      booster immunization with antigen. A similar increase in the number of rosetting
      B cells was also observed following in vitro culture of PBMC with antigen. These
      findings demonstrate that immunomagnetic bead selection serves as a specific and
      reliable approach in identifying and isolating antigen-specific B cells from
      human PBMC and provides a valuable method for studying T-B interactions in
      antigen-specific immune responses.

PMID- 7520375
TI  - The influence of DNA size on the binding of anti-DNA antibodies in the solid and
      fluid phase.
AB  - To elucidate the interaction of anti-DNA antibodies with DNA, the reactivity of
      lupus sera with single-stranded fragments from calf thymus, Escherichia coli, and
      salmon testes DNA was investigated. These fragments were generated by digestion
      with the restriction enzyme HinfI and ranged in size from approximately 100-4000
      bases. By ELISA using polystyrene microtiter plates, fragments from all three
      species were weakly antigenic compared to intact DNA. These fragments, however,
      were all antigenic when tested as inhibitors in competition-binding assays. The
      weak antigenicity of fragments could not be explained by poor adherence to the
      plates since fragments and intact DNA showed similar levels of binding as
      assessed using biotinylated preparations. Together, these results demonstrate
      that the antigenicity of DNA fragments is dramatically altered by solid-phase
      binding and suggest that constraints on topological or conformational
      rearrangements of DNA in the solid phase limit antibody interaction.

PMID- 7520376
TI  - Effect of IL-2 on immunoglobulin production by anti-CD40-activated human B cells:
      synergistic effect with IL-10 and antagonistic effect with IL-4.
AB  - Activation of B cells by anti-CD40 provides an excellent model to investigate the
      direct effect of various cytokines on Ig production. Using this culture system,
      we examined the effect of IL-2 alone or in combination with other cytokines. IL-2
      alone had only a moderate effect on Ig production by anti-CD40-activated B cells
      if compared with the effect of IL-10. However, IL-2 significantly augmented the
      synthesis of IgM, IgA, and IgG, including all IgG subclasses by anti-CD40
      activated B cells cultured in the presence of IL-10. Both IgD- and IgD+ B cells
      showed an increase of IL-10-induced Ig production if IL-2 was added to the
      culture. The addition of IL-2 also increased immunoglobulin synthesis by anti
      CD40/IL-10-activated B cells from patients with common variable immunodeficiency
      (CVI) and defective IL-2 production, suggesting that in a subgroup of CVI
      patients the IL-2 deficiency may contribute to the observed
      hypogammaglobulinemia. In contrast, the addition of IL-2 had a suppressive effect
      on IgE and IgG4 production by B cells cultured in the presence of anti-CD40 and
      IL-4. These data demonstrate that IL-2 plays an active role in the regulation of
      Ig production via CD40 by anti-CD40-activated B cells.

PMID- 7520378
TI  - Regulatory rearrangements and smg-sensitive alleles of the C. elegans sex
      determining gene tra-1.
AB  - The tra-1 gene is the terminal regulator in the sex determination pathway in C.
      elegans, directing all aspects of somatic sexual differentiation. Recessive loss
      of-function (lf) mutations in tra-1 masculinize XX animals (normally somatically
      female), while dominant gain-of-function mutations feminize XO animals (normally
      male). Most tra-1 (lf) mutations can be fitted into a simple allelic series of
      somatic masculinization, but a small number of lf alleles do not fit into this
      series. Here we show that three of these mutations are associated with DNA
      rearrangements 5' to the coding region. One allele is an inversion that may be
      subject to a position effect. We also report the isolation of a new class of tra
      1 alleles that are responsive to mutations in the smg system of RNA surveillance.
      We show that two of these express RNAs of aberrant size. We suggest that the smg
      sensitive mutations may identify a carboxy-terminal domain required for negative
      regulation of tra-1 activity.

PMID- 7520377
TI  - The immunoreactive region in a novel autoantigen contains a nuclear localization
      sequence.
AB  - Antibodies in the serum of patients with autoimmune diseases have been used to
      identify human autoantigens. Because autoantibodies often recognize active sites
      within corresponding protein antigens, autoantibodies have facilitated the
      functional characterization of these polypeptides. In the present study, serum
      from a patient with Sjogren's syndrome was used to identify a novel autoantigen
      which was designated Ge-1. Using the patient's serum, a 4.8-kb cDNA encoding Ge-1
      was identified. Fragments of the cDNA were ligated into prokaryotic expression
      vectors, expressed in Escherichia coli, and used to produce recombinant Ge-1
      fusion proteins. Fusion proteins containing different portions of Ge-1 were used
      to identify a 58 amino acid immunoreactive region within the protein. This
      immunoreactive region contained the protein's putative nuclear localization
      sequence (NLS). To demonstrate that the immunoreactive region was capable of
      functioning as a NLS, a eukaryotic expression plasmid was constructed to encode
      the immunoreactive region fused to the cytoplasmic protein, chicken muscle
      pyruvate kinase. After transfection of this plasmid into COS-1 cells, the fusion
      protein was detected in the nucleus. The presence of the NLS motif within the
      immunoreactive region of Ge-1 and other nuclear autoantigens suggests that the
      NLS may be a target of human autoantibodies.

PMID- 7520379
TI  - Association of cerebrospinal fluid deficiency of 5-methyltetrahydrofolate, but
      not S-adenosylmethionine, with reduced concentrations of the acid metabolites of
      5-hydroxytryptamine and dopamine.
AB  - 1. Folate deficiency, or inborn errors of folate metabolism, cause reduced
      turnover of 5-hydroxytryptamine (serotonin), and perhaps dopamine, in the central
      nervous system. The mechanism by which this occurs are not known. One possibility
      is that this is mediated by deficiency of the methyl-donor S-adenosylmethionine.
      2. To test this in humans, we have measured cerebrospinal fluid concentrations of
      5-hydroxyindoleacetic acid and homovanillic acid, metabolites of 5
      hydroxytryptamine and dopamine, respectively, in children with inborn errors of
      the methyl-transfer pathway. These children are naturally deficient in 5
      methyltetrahydrofolate, S-adenosylmethionine or both before treatment, and
      replete with S-adenosylmethionine, but not necessarily with 5
      methyltetrahydrofolate, during treatment. 3. Children with subnormal
      cerebrospinal fluid concentrations of 5-methyltetrahydrofolate had significantly
      reduced concentrations of 5-hydroxyindoleacetic acid and homovanillic acid.
      Children with subnormal cerebrospinal fluid concentrations of S
      adenosylmethionine did not have significantly reduced concentrations of these
      metabolites. 4. We conclude that the mechanism by which deficiency of 5
      methyltetrahydrofolate causes reduced 5-hydroxytryptamine and dopamine turnover
      is unlikely to be mediated by S-adenosylmethionine.

PMID- 7520381
TI  - Platelet-activating factor mediates pancreatic function derangement in caerulein
      induced pancreatitis in rats.
AB  - 1. We have assessed the role of platelet-activating factor in caerulein-induced
      acute pancreatitis (four subcutaneous injections of caerulein at a dose of 20
      micrograms/kg) by measuring platelet-activating factor levels in portal blood,
      pancreatic tissue and peritoneal exudate in rats with and without pancreatitis.
      2. We have also observed the effect of the platelet-activating factor antagonist,
      BN-52021, on the hyperamylasaemia and exocrine pancreatic secretion impairment
      associated with pancreatitis. 3. In rats with pancreatitis the basal pancreatic
      flow rate was increased (1.63 +/- 0.41 versus 0.25 +/- 0.03 microliters/min).
      Total protein output was similar in both untreated (5.98 +/- 1.93 micrograms/min)
      and caerulein-injected (6.5 +/- 2.0 micrograms/min) animals. Amylase output was
      lower in rats with pancreatitis (19.6 +/- 4.8 mu-units/min) than in controls
      (39.4 +/- 16.6 mu-units/min). 4. Caerulein-treated animals had significantly
      higher serum amylase levels than untreated animals. BN-52021 significantly
      reduced the caerulein-induced hyperamylasaemia. 5. Portal blood platelet
      activating factor levels increased in rats with pancreatitis and in rats infused
      with cholecystokinin. Rats injected with caerulein and BN-52021 had portal blood
      levels of platelet-activating factor that were lower than those with
      pancreatitis. 6. Morphological derangements associated with pancreatitis
      (inflammatory infiltration and cell vacuolization) were also markedly reduced in
      BN-52021-treated animals. 7. The results of this study suggest that platelet
      activating factor is involved in the development of caerulein-induced acute
      pancreatitis in rats.

PMID- 7520380
TI  - Urinary endothelin-1-like immunoreactivity in young male patients with testicular
      cancer treated by cis-platinum: comparison with other urinary parameters.
AB  - 1. Urinary excretion of endothelin-1-like immunoreactivity and urinary excretion
      of other parameters (beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase and
      microalbumin) were measured before, within 1 week after and 2 weeks after the
      administration of cis-platinum in five young male patients with testicular cancer
      (mean age 33.0 years) and were compared. 2. Urinary endothelin-1-like
      immunoreactivity/creatinine during, 1 week after, and 2 weeks after cis-platinum
      treatment was significantly higher than before cis-platinum. There was no
      difference in urinary endothelin-1-like immunoreactivity/creatinine during, 1
      week after and 2 weeks after cis-platinum. 3. Among the four parameters, urinary
      endothelin-1-like immunoreactivity/creatinine showed the highest level after cis
      platinum treatment. Urinary beta 2-microglobulin/creatinine most rapidly returned
      to normal levels after cis-platinum. 4. Although urinary endothelin-1-like
      immunoreactivity/creatinine did not show any significant correlations with
      urinary N-acetyl-beta-D-glucosaminidase (r = 0.291, not significant) or urinary
      microalbumin/creatinine (r = 0.076, not significant), it showed a significant
      correlation with urinary beta 2-microglobulin/creatinine (r = 0.475, P < 0.05).
      5. These results suggest that endothelin-1 may be a sensitive urinary parameter
      in detecting cis-platinum-induced renal tubular injury.

PMID- 7520382
TI  - Vi-specific latex agglutination for early and rapid detection of Salmonella
      serotype typhi in blood cultures.
AB  - Latex particles coated with rabbit antisera against Salmonella serotype typhi (S.
      typhi) Vi and O (STO) antigens were used in slide agglutination tests for the
      rapid identification of S. typhi in blood culture broths as soon as Gram-negative
      bacilli (GNB) were detected in them. Among 231 consecutive blood cultures showing
      GNB tested for Vi, and a subset of 163 tested for STO, by latex agglutination
      (LA), 125 and 32, respectively, were positive. The GNB in 127 blood cultures were
      confirmed by conventional methods as S. typhi, 125 (98.4%) of which had been
      identified by the Vi LA test. In the subset of 163, 81 grew S. typhi, of which
      only 32 (39.5%) had been identified by the STO LA tests. Thus, the sensitivity of
      the Vi and STO LA tests was 98.4% and 39.5%, respectively, whereas the
      specificity was 100% for both tests. Of the S. typhi isolates, 38 (30.4%) were
      detected by the Vi LA test on day 2 and 73 (58.4%) on day 3, day 1 being the date
      of inoculation of the blood culture broths. Thus, the Vi LA test is suitable for
      the early and rapid confirmation of S. typhi in blood culture.

PMID- 7520383
TI  - Ion transport across the isolated intestinal mucosa of Anguilla anguilla
      (Pisces).
AB  - The posterior intestine of freshwater-adapted Anguilla anguilla has a serosa
      negative transepithelial potential difference (TPD), and a current corresponding
      to the flow of negative current towards serosa. The TPD and the short-circuit
      current (SCC) were inhibited by Na+ and K+ withdrawal, and Cl- substitution or
      BA2+ addition inverts TPD and SCC, suggesting a Cl- and Na+ current mucosa
      serosa, a K(+)-Cl- cotransport and a K+ channel in the mucosal side. The TPD and
      SCC were inhibited by ouabain, DIDS, furosemide and amiloride, indicating the
      presence of a Na(+)-K(+)-ATPase, and Cl-/HCO3-,Na(+)-K(+)-Cl- and Na+/H+
      cotransporters.

PMID- 7520384
TI  - Action of intraduodenal ethanol on exocrine pancreatic secretion in chronic
      alcoholic rats fed with different diets.
AB  - The effects of diet composition (equilibrated and fat- and protein-rich) in
      combination with chronic ethanol ingestion on pancreatic exocrine secretion were
      studied in rats after a 7-month treatment period, also analyzing under these
      experimental conditions the acute effects of intraduodenal administration of 20%
      ethanol. Chronic consumption of ethanol affected pancreatic flow but its acute
      administration stimulated the secretion of fluid, especially in control rats.
      Total protein secretion is depressed in all rats receiving ethanol as fluid, but
      this was increased when rats drank water. Amylase activity depends on
      carbohydrate levels, decreased with fat and protein-rich diet but not with
      ethanol ingestion. Diet composition by itself did not affect specific trypsin
      activity but this increased significantly when a fat- and protein-rich diet was
      administered together with ethanol. Trypsin activity remained unchanged when
      ethanol was perfused into the duodenum in animals receiving ethanol chronically.

PMID- 7520386
TI  - [Treatment of advanced melanoma with a combination of interferon and
      chemotherapy].

PMID- 7520385
TI  - In vivo and in vitro growth-stimulatory effects of pigeon milk.
AB  - Pigeon milk (PM) was tested for its effect on growth in vivo and in vitro. Eleven
      day-old mice sucklings given a supplementary feeding of 125 mg PM per day for 3
      days showed a significant increase in the weight of stomach and distal intestine,
      and the length of small intestine; there was, however, a significant decrease in
      heart size. In PM-fed animals the protein content of stomach, and RNA content of
      stomach, caecum and distal intestine increased whereas protein content of testes
      and distal intestine and DNA content of stomach decreased. Crude homogenates of
      PM stimulated 3H-thymidine incorporation both in quiescent mouse embryo
      fibroblasts and Chinese hamster ovary cells. Addition of PM homogenates to cell
      cultures increased cell number but not protein content. The extent of in vitro
      growth-stimulation by 1% (v/v) PM homogenate was comparable to that by 2% (v/v)
      foetal bovine serum but was greater than that by 0.1 ng mouse epidermal growth
      factor. It appears that in mammalian test systems the in vitro growth-stimulatory
      effects of pigeon milk outweigh those observed in mice.

PMID- 7520388
TI  - Lyme disease: laboratory diagnosis and serologic testing.
AB  - Although identified less than 20 years ago, Lyme disease has proved to be the
      most common tick-borne disease in the United States: some 10,000 cases were
      reported in 1992. In some cases the disease may be transitory and of little
      consequence but in others it may become chronic and severely disabling. Accurate
      diagnosis is, therefore, of great importance but, as this article shows,
      laboratory testing techniques still need improvement.

PMID- 7520387
TI  - [Post-transfusion hepatitis C in Finland].

PMID- 7520390
TI  - Antisense RNA-mediated transcriptional attenuation occurs faster than stable
      antisense/target RNA pairing: an in vitro study of plasmid pIP501.
AB  - Antisense RNA-mediated transcriptional attenuation is the mode of replication
      control of several plasmids, among them pIP501. This mechanism implies that the
      repR mRNAs can fold into two mutually exclusive structures. The formation of one
      of these structures is induced by binding of the antisense RNA and results in
      premature termination. Since the fate of the nascent mRNA transcripts depends on
      the binding rate of the antisense RNA to its target, the control is kinetic. We
      have studied the antisense RNA, RNAIII, and target RNA, RNAII, whose interaction
      determines the replication frequency of plasmid pIP501. RNA secondary structures
      were analyzed using structure-specific RNases. RNA binding was studied in vitro
      with normal size and truncated RNAIII species. An in vitro single-round
      attenuation assay was developed that permits qualitative and quantitative
      assessment of inhibition by RNAIII. The effect of varying concentrations of
      RNAIII species on attenuation was tested and inhibition rate constants were
      calculated. The inhibition rate constants were at least 10 times higher than the
      pairing rate constants. Thus, steps preceding stable RNA duplex formation are
      sufficient to induce RNAIII-dependent termination of nascent RNAII transcripts.

PMID- 7520389
TI  - Characterization of a birch pollen allergen, Bet v III, representing a novel
      class of Ca2+ binding proteins: specific expression in mature pollen and
      dependence of patients' IgE binding on protein-bound Ca2+.
AB  - A cDNA coding for a birch pollen allergen, Bet v III, with significant sequence
      homology to Ca2+ binding proteins was isolated from an expression cDNA library
      using serum IgE from a patient who was allergic to pollen. The deduced amino acid
      sequence of the pollen allergen contained three typical Ca2+ binding sites.
      Peptides mimicking the Ca2+ binding sites of Bet v III were synthesized and shown
      to bind 45Ca in blot overlays. The binding of patients' IgE to the recombinant
      allergen depended on the native protein conformation and protein-bound Ca2+.
      Depletion of Ca2+ led to a reversible loss of the IgE binding thus representing a
      conformational IgE epitope adopted by a polypeptide upon Ca2+ binding. By RNA
      hybridization it was demonstrated that Bet v III is expressed preferentially in
      mature pollen. Bet v III therefore represents a pollen allergen which because of
      its unique structural features also belongs to a novel class of Ca2+ binding
      proteins.

PMID- 7520391
TI  - The molecular basis of canine pyruvate kinase deficiency.
AB  - Inherited hemolytic anemia due to pyruvate kinase (PK) deficiency is an autosomal
      recessive disease of the Basenji dog that closely resembles human PK deficiency.
      Characterization of transcriptional and translational expression of PK isozymes
      and sequencing of DNA from normal and mutant dogs were performed to identify the
      genetic defect in Basenji dogs. Measurement of erythrocytic PK activity by ion
      exchange chromatography, substrate kinetics, immunologic reactivity, and
      electrophoretic mobility suggests that M2-type PK is the major form of PK
      activity in erythrocytes of PK-deficient dogs, in contrast to normal dogs having
      only R-type PK activity. Both R-type and M2-type PK mRNA are detectable in
      reticulocytes of PK-deficient dogs, suggesting that the aberrant isozyme
      expression is not due to a failure in the erythroid maturational switch from M2-
      to R-type isozymes. Nucleotide sequence data from wild-type and mutant R-type PK
      cDNA identified a single nucleotide deletion, delta C433, in the mutant cDNA. The
      deduced amino acid sequence predicts a truncated mutant protein devoid of all
      residues contributing to the catalytic site of the wild-type protein. In the
      absence of R-type PK activity, there is anomalous compensatory expression of M2
      type PK in erythroid cells of PK-deficient Basenjis. The PK-deficient Basenji dog
      may be valuable in somatic cell gene therapy trials involving manipulation of
      hematopoietic stem cells.

PMID- 7520393
TI  - Transforming growth factor-beta regulates the cell cycle status of interleukin-3
      (IL-3) plus IL-1, stem cell factor, or IL-6 stimulated CD34+ human hematopoietic
      progenitor cells through different cell kinetic mechanisms depending on the
      applied stimulus.
AB  - The immediate cell kinetic response of highly purified human bone marrow
      progenitor cells (CD34+ sorted fraction) to the inhibitory effects of
      transforming growth factor-beta (TGF-beta) was studied using the BrdU-Hoechst
      flow-cytometric technique. The progenitor cells were stimulated with either
      interleukin-3 (IL-3) alone or with IL-3 in combination with IL-1, stem cell
      factor (SCF), or IL-6, and the inhibitory action of TGF-beta was evaluated in
      each phase of the first three consecutive cell cycles. Semisolid methylcellulose
      cultures were also performed to compare these initial events to the effects
      observed after 7, 14, and 21 days of incubation. Within the CD34+ compartment,
      the progenitor cells can be discriminated on a functional basis, i.e., in terms
      of TGF-beta sensitivity. Very primitive progenitors, recruited out of the G0
      phase by IL-3 plus an early-acting factor (IL-1, SCF) are, upon addition of TGF
      beta, arrested specifically in the G1 phase of the second cell cycle. In the
      clonogenic assays, the increased colony formation due to IL-1 or SCF was
      completely abolished by the counteracting effect of TGF-beta that diminished
      colony output back to the level of TGF-beta-plus-IL-3 supplemented colony growth.
      Addition of TGF-beta to CD34+ progenitors responding to IL-3 alone resulted in an
      overall retardation, but without an apparent specific accumulation of cells in
      any of the cell cycles. Finally, within the CD34+ compartment, there exists a
      subset of IL-3-responsive, but TGF-beta-insensitive, progenitor cells that were,
      upon addition of TGF-beta, not arrested at all. In conclusion, our results
      demonstrate that TGF-beta exerts different cell kinetic effects on CD34+
      progenitor cell growth depending on the applied stimulus.

PMID- 7520392
TI  - Cell processing protocol for allogeneic peripheral blood stem cells mobilized by
      granulocyte colony-stimulating factor.
AB  - Although there is a growing body of information available regarding restoration
      of hematopoiesis with peripheral blood stem cell (PBSC) autografts, few studies
      have explored this procedure using allografts. In this study with healthy donors,
      we investigated the feasibility of a protocol for mobilizing PBSC using
      recombinant human granulocyte colony-stimulating factor (G-CSF) and subsequent
      bulk depletion of T cells from apheresis-harvested cells. Nine informed healthy
      donors were given G-CSF subcutaneously at two different dosing schedules (5
      micrograms/kg/d in five donors and 2 micrograms/kg/d in four) for 5 consecutive
      days, and serial changes in blood components, including hematopoietic progenitor
      cells, were monitored. After 5 days of stimulation with G-CSF, PBSCs were
      collected by apheresis, and yields were compared. The number of white blood cells
      (WBC) reached a plateau level on either day 2 (5 micrograms) or 3 (2 micrograms),
      but the numbers of red blood cells and platelets were not affected. Circulating
      colony-forming unit-granulocyte/macrophage (CFU-GM) levels started to increase 1
      or 2 days after the increase in the WBC count. By performing a 3L apheresis, the
      number of CFU-GM harvested was 4.6 +/- 3.3 x 10(6) (mean +/- standard error of
      the mean [SEM]) in the 5-micrograms group and 1.8 +/- 0.7 x 10(6) in the 2
      micrograms group. Different procedures for depleting T cells, including the use
      of L-phenylalanine methyl ester (PME) and flasks coated with anti-CD5/CD8
      monoclonal antibodies or neuraminidase-treated sheep red blood cells (SRBC), were
      also tested on the harvested cells. We found that cell lysis with PME before
      selective removal of T cells was very effective in reducing the number of cells
      that required further processing and was suitable for routine use. However, our
      current procedure resulted in unsatisfactory depletion of T cells (99.5% removal)
      while retaining hematopoietic progenitor cells (7.5% recovery). Further research
      is required in this area.

PMID- 7520395
TI  - In vitro fertilization in couples with previous fertilization failure using sperm
      incubated with pentoxifylline and 2-deoxyadenosine.
AB  - OBJECTIVE: To evaluate whether incubation of spermatozoa with both pentoxifylline
      and 2-deoxyadenosine would improve fertilization rates in couples with previous
      IVF failure. DESIGN: Autocontrolled design in which sibling oocytes were
      inseminated at random in vitro with spermatozoa treated or not treated by
      pentoxifylline and 2-deoxyadenosine. MEAN OUTCOME MEASURES: Oocyte quality, sperm
      motility, fertilization in vitro, and embryo quality. RESULTS: Sperm motility was
      found optimized by metabolic stimulation using pentoxifylline and 2
      deoxyadenosine. The mean fertilization rate per patient was 33.1% in the
      treatment group compared with 37.0% in the control group. The mean cleavage rate
      per patient was 79.6% for treatment versus 68.7% for control embryos. No
      differences in embryo quality were noted. CONCLUSION: The results of this study
      demonstrate that an indiscriminate use of pentoxifylline and 2-deoxyadenosine is
      not beneficial to fertilization in couples with previous IVF failure. Further
      prospective research may be needed to assess the benefit of pentoxifylline and 2
      deoxyadenosine in patients selected by preliminary functional in vitro tests.

PMID- 7520396
TI  - Efficacy of treatment and recurrence rate of leukocytospermia in infertile men
      with prostatitis.
AB  - OBJECTIVE: To identify men with leukocytospermia and prostatitis in an
      infertility practice and evaluate the effect of various treatments and recurrence
      rates after treatment. DESIGN: A prospective randomized trial of men with
      leukocytospermia. SETTING: Academic tertiary infertility clinic. PATIENTS: One
      hundred two men with leukocytosperimia identified on smear of semen using Bryan
      Leishman stain and in expressed prostatic secretion. INTERVENTIONS: Treatment
      groups were no treatment group; antibiotic treatment alone group; frequent
      ejaculation alone group; and antibiotic treatment with frequent ejaculation
      group. MAIN OUTCOME MEASURE: Resolution of leukocytospermia on semen smear.
      RESULTS: Significant resolution of leukocytospermia occurred in all treatment
      groups at 1 month compared with no treatment. The resolution was sustained at 2
      and 3 months only in those who took antibiotics and frequently ejaculated.
      CONCLUSIONS: Antibiotic treatment, frequent ejaculation, and antibiotic treatment
      with frequent ejaculation effectively treat leukocytospermia immediately after
      the treatment phase. However, only antibiotic treatment coupled with frequent
      ejaculation is effective 3 months after treatment.

PMID- 7520394
TI  - Stem cell factor (c-kit ligand) enhances the interleukin-9-dependent
      proliferation of human CD34+ and CD34+CD33-DR- cells.
AB  - We have studied the effects of recombinant human interleukin-9 (IL-9), alone and
      combined with stem cell factor (SCF, c-kit ligand), IL-3, and granulocyte
      macrophage colony-stimulating factor (GM-CSF) on the clonogenic proliferation of
      highly enriched human hematopoietic CD34+ and CD34+CD33-DR- progenitor cells.
      Colony assays were performed under serum-containing and serum-free conditions. IL
      9, as a single agent, did not support colony formation. The addition of
      erythropoietin (Epo) to IL-9 induced the growth of erythroid progenitors (BFU-E)
      derived from both CD34+ and CD34+CD33-DR- cells. The IL-9-dependent growth of BFU
      E derived from CD34+ cells was increased in an additive manner by SCF and, to a
      lesser extent, by IL-3, whereas CD34+CD33-DR- erythroid precursors were also
      responsive to GM-CSF in combination with IL-9. The addition of SCF to IL-9 did
      stimulate the development of CD34+ and CD34+CD33-DR- macroscopic, multicentered
      BFU-E and multilineage colonies (CFU-GEMM). When IL-9 was used in serum-free
      conditions, the growth of CD34+ and CD34+CD33-DR- BFU-E was observed in the
      presence of Epo. Moreover, a marked synergy on BFU-E colony formation was evident
      when IL-9 was combined with SCF, and their activity was enhanced by the addition
      of IL-3. IL-9 showed a negligible proliferative activity on colony-forming units
      granulocyte/macrophage (CFU-GM). However, it increased the number of CD34+CD33-DR
      CFU-GM responsive to IL-3 (37% of the colonies generated by phytohemagglutinin
      stimulated lymphocyte conditioned medium [PHA-LCM]). The effects of IL-9 on
      CD34+CD33-DR- cells were also studied in a short-term suspension culture system,
      which evaluates the proliferation of progenitors earlier than day 14 CFU-C (Delta
      assay). In this system, IL-9 had a minimal activity on its own. In combination
      with SCF, however, it induced a nine-fold expansion of CD34+CD33-DR- cells, which
      generated a greater number of CFU-GM than BFU-E in secondary methylcellulose
      cultures. These experiments indicate that IL-9 induces the proliferation of very
      primitive human erythroid cells, and this effect is potentiated by SCF and other
      cytokines. Furthermore, IL-9 synergizes in vitro with the c-kit ligand in
      expanding the pool of early pluripotent hematopoietic progenitor cells.

PMID- 7520397
TI  - Induction of heat shock protein and prevention of caerulein-induced pancreatitis
      by water-immersion stress in rats.
AB  - Water-immersion stress is known to be involved in the development of hemorrhagic
      pancreatitis in caerulein-induced pancreatitis, when the stress is given
      following caerulein injection. The effects of pre-treatment with water-immersion
      to caerulein-induced pancreatitis were investigated in this study. 1. A 60-kDa
      heat shock protein was induced by pre-treatment with water-immersion stress in
      the pancreas. 2. Intra-peritoneal injection of caerulein (40 micrograms/kg)
      induced acute pancreatitis in rats without pre-treatment with water-immersion.
      However, when the rats were pre-treated with water-immersion, acute pancreatitis
      was not developed and no change of serum amylase levels was observed by i.p.
      injection of caerulein.

PMID- 7520399
TI  - Pancreatic exocrine secretion in short-term pancreatic duct obstruction induced
      acute pancreatitis in rats: an in vivo and in vitro study.
AB  - We investigated digestive enzyme release following a short-term pancreatic duct
      obstruction in rats. An in vivo experiment demonstrated that a 6-hour pancreatic
      duct obstruction reduced digestive enzyme release evoked both by endogenously
      released cholecystokinin (CCK) due to pancreaticobiliary diversion and by
      exogenous administration of CCK8. In vitro experiments also showed that
      pancreatic duct obstruction reduced the maximal CCK8-evoked amylase secretion.
      Amylase secretion evoked by the calcium ionophore A23187 and by phorbol myristate
      acetate was also markedly decreased. These data suggest that pancreatic duct
      obstruction probably interferes with the secretory process downstream of hormone
      receptor binding, intracellular Ca2+ release and protein kinase C activation.

PMID- 7520400
TI  - Implication of cholecystokinin in pancreatic adaptation after biliopancreatic
      bypass in the rat.
AB  - Biliopancreatic bypass (BPB), a bariatric surgical procedure, leads to a
      malnutrition-induced general visceral atrophy except for the pancreas. This work
      investigates the implication of cholecystokinin (CCK) in the exocrine pancreatic
      adaptive process using a plasma CCK assay and the CCK receptor antagonist CR
      1409. No significant reduction in weight and DNA content of the pancreas was
      noted 36 days after BPB, while a strong decrease in protein, enzymes and RNA
      contents indicating cellular hypotrophy became apparent. CR 1409 treatment
      strongly depressed pancreatic weight and its DNA content in BPB animals,
      suggesting an additional hypoplasia; however, the reduction in pancreatic enzyme
      content was not aggravated. BPB increased plasma CCK concentrations by 160%,
      unrelated to CR 1409 treatment. These results indicate that: (1) CCK is involved
      in the pancreatic adaptive response after BPB in rats, and (2) in the context of
      a protein malnutrition state, CCK dissociates its pancreatic growth and enzymatic
      effects, favouring the former.

PMID- 7520398
TI  - Oligoclonal beta-galactoside-binding immunoglobulins antigenically related to 14
      kDa lectin in human serum and cerebrospinal fluid: purification and
      characterization.
AB  - 1. An antiserum raised against a 14 kDa beta-galactoside specific lectin from
      human brain (HBL14) was used to probe blots from samples of serum and
      cerebrospinal fluid. The only HBL14-immunoreactive material detected was heavy
      and light chains of a beta-galactoside-binding IgG fraction (lectin-like IgG). 2.
      Lectin-like IgG, as well as IgG Fab fragments, compete with HBL14 for binding
      either to anti-HBL14 antibody or to a lactosyl polyacrylamide-based copolymer. 3.
      Purification of lectin-like IgG was obtained by affinity chromatography on
      immobilized rabbit anti-lectin immunoglobulins. The carbohydrate-binding
      specificity of the purified molecules was restricted to beta-Gal-containing
      structures and close to the HBL14 one.

PMID- 7520402
TI  - Platelet-activating factor involvement in the aggravation of acute pancreatitis
      in rabbits.
AB  - Platelet activating factor (PAF) was administered to anesthetized rabbits with
      cerulein-induced acute pancreatitis to investigate the role of PAF in the
      development of acute pancreatitis. In acute edematous pancreatitis, induced with
      cerulein 20 micrograms/kg/h i.v. for 5 h, blood flow in the gastroduodenal and
      superior mesenteric arteries (GDAF and SMAF) had decreased significantly by 30
      min and the serum amylase and lipase levels were significantly increased in the
      early phase. In the cerulein+PAF group, in which PAF was injected 100 ng/kg/min
      i.v. for 20 min simultaneously with cerulein, GDAF and SMAF declined
      significantly to 52 +/- 4 and 47 +/- 3% (p < 0.05), serum amylase and lipase
      levels rose significantly to 1,110 +/- 150 and 1,370 +/- 190% (p < 0.01) at 300
      min, much higher than in the cerulein group. Furthermore, scattered hemorrhages
      and more marked inflammatory cell infiltration were observed histologically.
      These findings suggest that PAF has an additive role in the aggravation of acute
      pancreatitis.

PMID- 7520401
TI  - Molecular and functional characterization of insulin receptors present on hamster
      glucagonoma cells.
AB  - Studies using pancreas perfusion techniques point to a physiological inhibition
      of glucagon release by insulin which should be mediated by A cell-residing
      insulin receptors. In this study, we have characterized the insulin receptors
      expressed in a hamster glucagonoma A cell line (INR1G9 cells) which is an
      accepted tool for A cell studies. In receptor binding assays 125I-insulin was
      displaced with a Kd of 3 nmol/l. Binding was also dependent upon time,
      temperature and cell number. Insulin concentration-dependently inhibited glucagon
      secretion (1 mumol: 59%, 100 nmol/l: 71%, 10 nmol/l: 86% of controls). In
      transient transfection experiments insulin inhibited proglucagon gene
      transcription (controls: 100%, 100 nmol/l: 54%, 10 nmol/l: 57%, 1 nmol/l: 72%,
      100 pmol/l: 96%). Treatment of INR1G9 cells with insulin for 20 h induced a
      strong downregulation of insulin receptors (controls: 100%, 100 nmol/l: 30%, 10
      nmol/l: 70%, 1 nmol/l: 73%, 100 pmol/l: 75%) and of insulin receptor mRNA levels
      (controls: 100%, 100 nmol/l: 42%, 10 nmol/l: 82%, 1 nmol/l: 84%, 100 pmol/l:
      90%). When INR1G9 cells were transiently transfected with a hybrid gene
      containing the promotor/enhancer region of the human insulin receptor promotor
      (1,462 bp) linked to the transcriptional reporter gene chloramphenicol
      acetyltransferase and were treated with insulin it was demonstrated that insulin
      did not affect the insulin receptor gene transcription. In conclusion, INR1G9
      cells express specific receptors for insulin. Insulin inhibits glucagon secretion
      and proglucagon gene expression via an inhibition of proglucagon gene
      transcription. Ligand-induced downregulation of the insulin receptor is not
      mediated by changes of insulin receptor gene transcription and is most likely
      regulated by posttranscriptional mechanisms, e.g. destabilization of insulin
      receptor mRNA.

PMID- 7520403
TI  - Sequence analysis of the ribosomal RNA operon of the Lyme disease spirochete,
      Borrelia burgdorferi.
AB  - An 11,955-bp region of the Borrelia burgdorferi chromosome containing all the
      genes encoding ribosomal RNA (rRNA) has been sequenced. The region contains a
      single gene encoding 16S rRNA and two genes encoding the 23S and 5S rRNAs. The
      sizes of the 16S, 23S and 5S rRNAs encoded by these genes are 1537, 2926 and 112
      nucleotides, respectively. In addition, the genes encoding tRNA(Ala) and
      tRNA(Ile) are located in the intergenic spacer between the 16S and 23S rDNAs. The
      tDNAs do not encode the common CCA 3' end which presumably must be added
      posttranscriptionally. All the genes are present in the same orientation, except
      for that encoding tRNA(Ile), which is transcribed from the opposite strand. The
      latter implies that the rDNAs are not transcribed as a single unit. The location
      of putative promoters and termination signals in the sequence suggest that the
      16S rRNA and tRNA(Ala) are transcribed as a single unit, tRNA(Ile) is produced as
      an individual transcript and the 23S and 5S rDNAs are co-transcribed. Several of
      the features of this rDNA organization are unique, not having been described
      previously in any other eubacteria.

PMID- 7520404
TI  - [Assessment of the chronic effect of diesel engine emission on the etiology of
      immune reaction in animals].

PMID- 7520405
TI  - [Structural-functional changes in the liver and immunocompetent organs under the
      action of diamines].

PMID- 7520406
TI  - Damage of amino acids and proteins induced by nitrogen dioxide, a free radical
      toxin, in air.
AB  - Damage of amino acids and proteins induced by nitrogen dioxide, a free radical
      toxin in polluted air, was investigated. When nitrogen dioxide (30-90 ppm) in air
      was exposed to a solution of an amino acid at pH 7.5 for several hours,
      tryptophan and tyrosine were damaged. Degradation of tryptophan was accompanied
      by formation of a nitroindole derivative. Decrease of tyrosine was accompanied by
      formation of 3-nitrotyrosine and fluorescent dityrosine. When nitrogen dioxide
      was exposed to a solution of bovine serum albumin, human gamma-globulin and
      bovine eye lens alpha-crystallin, the proteins were crosslinked by nondisulfide
      bonds. Tryptophan and tyrosine residues in the proteins were extensively
      decreased, and significant amounts of 3-nitrotyrosine and fluorescent dityrosine
      were formed. The modification of the proteins with nitrogen dioxide in air may
      have toxicological significance. Because fluorescent dityrosine is detected in a
      wide variety of natural proteins, nitrogen dioxide may play a role in its
      occurrence in natural proteins.

PMID- 7520407
TI  - Cytotoxic drug sensitivity testing of tumor cells from patients with ovarian
      carcinoma using the fluorometric microculture cytotoxicity assay (FMCA).
AB  - The automated fluorometric microculture cytotoxicity assay (FMCA) is based on the
      measurement of fluorescence generated from cellular hydrolysis of fluorescein
      diacetate (FDA) to fluorescein by viable cells after a 72-hr culture period in
      microtiter plates. The FMCA was adopted for chemosensitivity testing of tumor
      cells from patients with ovarian carcinoma. Thirty-seven samples of solid tumors
      and malignant effusions were obtained from 35 patients at diagnosis or relapse.
      Tumor cells from solid samples and effusions were prepared by enzymatic digestion
      and centrifugation, respectively, followed by Percoll or Ficoll purification. The
      fluorescence was proportional to the number of cells/well and considerably higher
      in tumor cells than in contaminating normal cells. The effect of up to 19
      cytotoxic drugs was successfully assessed in 70% of the samples and there was a
      good correlation between drug sensitivity data reported by the FMCA and the DiSC
      assay performed in parallel. The overall drug sensitivity pattern in vitro
      corresponded well to the clinical experience. The effect of cisplatin varied
      considerably between patients and resistance was found also in cases not
      previously exposed to cytotoxic drugs. The FMCA is a rapid and simple method that
      seems to report clinically relevant cytotoxic drug sensitivity data in ovarian
      carcinomas. In the future, this method may contribute to optimizing chemotherapy
      by assisting in individualized drug selection and new drug development.

PMID- 7520408
TI  - Immunological characterization of blood group A epitopes expressed on cells and
      tissues with a monoclonal anti-CEA antibody.
AB  - BACKGROUND AND METHODS: Monoclonal antibodies (mAb) specific for the
      oligosaccharide epitopes of glycoproteins or glycolipids, such as blood group
      antigens, are powerful tools for studying the antigenic structure of normal and
      pathological cells and tissues. Anti-A human red blood cell monoclonal antibodies
      were produced by immunizing mice with normal cells, but only a few fulfilled the
      conditions necessary for revealing qualitative differences among A-antigens. Only
      those produced by hybridomas obtained from mice immunized with human tumor
      antigens specifically recognize A1 and A2 blood group antigens. We report here
      several immunological properties of the A-antigen defined by a mAb raised against
      the tumor-associated carcinoembryonic antigen. RESULTS AND CONCLUSIONS: The
      hybridoma B2C114, obtained as a result of the fusion of spleen cells from mice
      immunized with the carcinoembryonic antigen and a murine myeloma cell line,
      produces a mAb which reacts specifically against erythrocytes bearing the A blood
      group antigen. The monoclonal antibody showed a high stability and a low
      dissociation rate from the antigen/antibody complex formed with adult A1, A2, A2B
      and cord blood samples. The antibody was able not only to discriminate between A1
      and A2-RBC but also to detect kinetic differences among A-sites. On the one hand
      B2C114, reactive with the glycosidic moiety of the A-antigen, can discern at
      least two qualitatively different epitopes expressed on the A1-RBC surface, with
      a total number of A sites that is in close agreement with the figures already
      described for A1-RBC. On the other hand, A2-RBC shows a single phenotype that is
      kinetically similar to A1-low affinity binding sites. This antibody also labelled
      spontaneous and chemically-induced murine tumors as well as human tumors. Its
      reactivity with colon carcinoma frozen specimens obtained from O- and B-blood
      group patients indicated expression of an incompatible A-antigen. The
      immunochemical properties of B2C114 described here give support to our purpose of
      employing this mAb as a blood group reagent as well as a histopathological probe
      for in vitro and in vivo cancer diagnosis.

PMID- 7520409
TI  - Expression and function of L-selectin molecules (LECAM-1) in B-cell chronic
      lymphocytic leukemia.
AB  - BACKGROUND: The notion that adhesion molecules play a crucial role in
      lymphoma/leukemia dissemination is widely accepted. Individual cases of B-cell
      chronic lymphocytic leukemia (B-CLL) show well-defined variables in the extent
      and pattern of peripheral blood and nodal involvement. The L-selectin adhesion
      molecule (TQ1/Leu-8, LAM series and LECAM-1) initiates the attachment of
      lymphocytes to the high endothelial venules (HEVs), and as a consequence the
      entrance of lymphocytes from the blood into the peripheral lymph node
      (recirculation which may be operative in lymphoma/leukemia dissemination as
      well). MATERIALS AND METHODS: The constitutional expression of L-selectin
      molecules (LECAM-1) on peripheral blood mononuclear cells (PBMCs) from B-CLL (16
      cases) was examined and correlated with receptor function in an HEV-binding assay
      and in a ligand immobilization test. RESULTS AND CONCLUSIONS: A correlation was
      found between constitutional expression and function of the L-selectins, namely
      the higher the number of cells expressing L-selectin molecules at a measurable
      level on the cell surface, the greater the number of cells showing attachment in
      the tests. It is suggested that many aspects of the biological and clinical
      heterogeneity of B-CLL will be explained by revealing the exact adhesion profile
      and function in different subtypes of the disease.

PMID- 7520410
TI  - Acute non lymphoid-leukemia with unusual staining of blasts.

PMID- 7520411
TI  - The expression of the B-cell marker mb-1 (CD79a) in Hodgkin's disease.
AB  - Recent evidence indicates that membrane-bound immunoglobulin on B lymphocytes is
      associated with a molecule which comprises the products of the mb-1 and B29
      genes. This molecule is a highly specific marker for B-cells, presumably because
      of its central functional role in antigen triggering, and has recently been
      clustered as CD79a at the 5th Leucocyte Workshop. Recently there has been
      controversy surrounding reports of B-cell antigen expression by Reed-Sternberg
      and related cells, and we have therefore studied 108 cases of Hodgkin's disease
      immunohistochemically using a novel antibody which detects mb-1 protein in
      paraffin sections. The results were compared with those achieved using antibody
      L26 to detect CD20. The mb-1 protein was present in the neoplastic cells in all
      14 cases of lymphocyte predominance Hodgkin's disease studied, and CD20
      immunoreactivity was also found in seven of the eight cases of this subtype
      studied. Of the non-lymphocyte predominance cases, 20% (19/94) expressed mb-1 and
      30% (20/67) CD20 in the Reed-Sternberg cells, but the cells positive for either
      of these two markers usually constituted only a very small proportion of the
      neoplastic population. However, in occasional cases (one of 94 for mb-1 and five
      of 67 for CD20), more than 50% of the neoplastic cells expressed one or both B
      cell antigens. These results confirm the B-cell origin of the neoplastic cells in
      lymphocyte predominance Hodgkin's disease, but they also indicate that, contrary
      to our previous study, mb-1 expression may occasionally be found in what appears,
      on histological grounds, to be other types of Hodgkin's disease.

PMID- 7520414
TI  - Medullary carcinoma of the breast: a tumour lacking keratin 19.
AB  - The presence of keratin 19 (K19) was searched for by immunostaining in 16
      medullary carcinomas, comprising 12 typical and four atypical cases, in 29
      undifferentiated high-grade carcinomas (NOS-HG) with conspicuous lymphoid
      response and in 12 well differentiated low-grade carcinomas (NOS-LG). The
      medullary carcinomas were all negative whereas 23 of the high-grade and all 12
      low-grade carcinomas expressed K19. Staining for K19 could be of value in the
      differential diagnosis of these tumours. Furthermore, these findings, with other
      observations, raise the possibility that medullary carcinoma cells could be
      linked to precursor cells of the terminal duct lobular units because both
      populations share several characteristics.

PMID- 7520413
TI  - Myoepithelial carcinoma of the breast with distant metastasis and accompanied by
      adenomyoepitheliomas.
AB  - A breast tumour in a 47-year-old female with axillary lymph node metastasis was
      interpreted as the rare malignant adenomyoepithelioma based on morphological and
      immunohistochemical studies. Multiple bone metastases developed and the patient
      died after 7 months. The malignant neoplasm consisted of cords and interlacing
      bundles of spindle cells with indistinct cell borders and clear cytoplasm. The
      cells stained positively for cytokeratin, S-100 protein, GFAP, and muscle
      specific actin, and possessed basal lamina, pinocytic vesicles, tonofilaments,
      desmosomes, and intermediate filaments with dense bodies. In some areas, cells
      with microvillous projections enclosed small spaces. In the breast, foci of
      myoepithelioma with various morphological subtypes and infiltration coexisted,
      demonstrating the origin of the malignant tumour. The histogenesis of the
      myoepithelial tumours is discussed.

PMID- 7520412
TI  - The histopathological features of asymptomatic hepatitis C virus-antibody
      positive blood donors.
AB  - Since the introduction of screening for hepatitis C virus (HCV) in donated blood,
      the risk of contracting posttransfusion hepatitis has been greatly reduced and
      the test has led to the recognition of asymptomatic blood donors positive for
      anti-HCV antibodies. Following confirmation of the HCV status with second
      generation RIBA testing followed by counselling, 55 patients had full
      investigations, including liver biopsy. These were classified by the traditional
      chronic hepatitis system and were graded according to the Knodell and Scheuer
      histological activity indices. Seven of the biopsies were normal (12%), apart
      from minor degrees of steatosis in two. Eleven cases (20%) were in the chronic
      lobular hepatitis category without portal inflammation, while 37 cases showed
      portal inflammation, including 20 (36%) cases where chronic persistent hepatitis
      was the predominant feature and 17 cases (31%) where there was chronic active
      hepatitis with piecemeal necrosis. Features which have previously been described
      in chronic HCV-associated hepatitis were noted: portal lymphoid aggregates (58%),
      lymphoid follicles with germinal centres (15%), bile duct damage (11%), lobular
      inflammation (80%), sinusoidal mononuclear cell infiltration (26%), acidophil
      body formation (11%), and steatosis (47%). Fibrosis was present in 46% of cases
      but was generally of mild degree; 9% of biopsies demonstrated bridging fibrosis
      but no cases of cirrhosis were present. Even though serum transaminase levels
      correlated well with the presence of chronic hepatitis and with the Scheuer and
      Knodell activity indices, a proportion of patients with significant liver damage
      had normal transaminase levels, and this study suggests the need for liver biopsy
      in the evaluation of asymptomatic HCV-positive blood donors.

PMID- 7520415
TI  - MC540 induced photosensitization of glioma & neuroblastoma cells.
AB  - Binding and photodynamic action of merocyanine 540 (MC540) has been studied in
      glioma (U-87MG) and neuroblastoma (Neuro 2A) cells as a function of dye
      concentration, incubation time of cells with MC540 and growth phase of cells. In
      the plateau phase, U-87MG cells accumulated more MC540 as compared to
      exponentially growing cells, whereas in Neuro 2A cells the opposite effect was
      observed. Exponentially growing U-87MG cells were more photosensitive than
      plateau phase cells. However, the photosensitivity of Neuro 2A cells was not
      dependent on the growth phase. Thus, MC540 mediated photosensitization may be
      useful for photodynamic therapy of brain tumours.

PMID- 7520416
TI  - Immunogenic and antigenic properties of a heptavalent high-molecular-weight O
      polysaccharide vaccine derived from Pseudomonas aeruginosa.
AB  - We investigated the chemical and immunologic properties of a heptavalent vaccine
      composed of high-molecular-weight polymers of the lipopolysaccharide (LPS) O
      polysaccharides representative of the most common clinical isolates of
      Pseudomonas aeruginosa. We also evaluated the serum antibody response to
      nonvaccine strains of P. aeruginosa, including strains expressing structural
      variants (subtype strains) of the O side chain of the vaccine strains. The
      polyvalent vaccine, prepared under conditions suitable for human use, contained
      low levels of contaminants and passed preclinical safety and toxicity tests
      required for human use. Chemical analyses indicated that individual
      polysaccharides were composed of both O-side chain and core sugars. Following
      immunization of C3H/HeN mice and New Zealand White rabbits, antibody titers
      against vaccine components increased between 32- and 200-fold. Antibodies
      reactive with LPS isolated from smooth and rough nonvaccine strains were also
      elicited. Analysis of the opsonic activity against the known LPS subtype variants
      of the vaccine strains revealed a variable pattern of killing, which ranged from
      opsonic killing of > or = 69% of bacterial cells representing all subtype
      variants within a serogroup to opsonization of only a minority of the subtype
      variant strains. Mouse and rabbit immune sera showed different patterns of
      opsonic activity against subtype strains, indicating that different epitopes on
      these antigens are immunodominant in the representatives of these two animal
      species tested. The polyvalent vaccine was effective at eliciting antibodies to
      vaccine components in mice and rabbits, but it remains to be determined if the
      current heptavalent formulation contains sufficient components to provoke human
      antibodies reactive with a majority of clinical strains of P. aeruginosa.

PMID- 7520417
TI  - Outer surface lipoproteins of Borrelia burgdorferi stimulate nitric oxide
      production by the cytokine-inducible pathway.
AB  - The outer surface lipoproteins of Borrelia burgdorferi, OspA and OspB, stimulate
      the production of nitric oxide (NO) by murine bone marrow-derived macrophages
      from BALB/c, C3H/HeN, and C3H/HeJ mice. Gamma interferon (IFN-gamma) caused a
      three- to fivefold enhancement of this production of NO, and the L-arginine
      analog N-guanidino-monomethyl L-arginine inhibited it. Activation of
      transcription of the inducible NO synthase gene in stimulated macrophages was
      demonstrated by reverse transcriptase rapid PCR. Although IFN-gamma increased the
      amount of NO produced in macrophage cultures, it did not cause transcription of
      the inducible NO synthase gene greater than that seen with the Borrelia proteins.
      OspA and OspB also induced the production of high levels (40 to 150 ng/ml) of IFN
      gamma in cultures of macrophages incubated with interleukin-2 (IL-2)-elicited
      cells from normal (T and NK cells) and scid (NK cells) mice but not in
      macrophages or IL-2-elicited cells cultured individually. This suggests that OspA
      stimulated macrophage production of cytokines, which, in turn, stimulated the
      production of IFN-gamma by NK and T cells. Reverse transcriptase rapid PCR
      demonstrated that OspA and sonicated B. burgdorferi stimulated production of
      several inflammatory cytokines in macrophage cultures, including IL-1, IL-6, IL
      12, IFN-beta, and tumor necrosis factor alpha. As tumor necrosis factor alpha,
      IFN-beta, and IL-12 are potent activators of IFN-gamma production by T and NK
      cells, their presence in these cocultures could be responsible for the IFN-gamma
      production. Lymphocytes from infected C3H mice also produced IFN-gamma when
      stimulated with B. burgdorferi; thus, immune cells may also modulate NO
      responses. The generation of NO during infection with B. burgdorferi may be
      important, as NO has potent antimicrobial properties. NO can also be involved in
      pathological inflammatory processes in which its generation is detrimental to the
      host. Thus, the colocalization of B. burgdorferi lipoproteins, NO-producing
      cells, and regulatory cytokines may determine the outcome of infection.

PMID- 7520419
TI  - Epitopes of the Onchocerca volvulus RAL1 antigen, a member of the calreticulin
      family of proteins, recognized by sera from patients with onchocerciasis.
AB  - RAL1 is an antigen (Ag) encoded by the filarial nematode Onchocerca volvulus, the
      parasite causing onchocerciasis (river blindness). RAL1 shares 64.4% identity
      with the autoantigen calreticulin. The striking similarity of the parasite Ag and
      the human autoantigen has led to the hypothesis that RAL1 may induce a cross
      reactive immune response to calreticulin, which in turn may be involved in the
      pathogenesis of onchocerciasis. To test this hypothesis, we explored the immune
      response to RAL1 recombinant Ag (RAL1 rAg) and human calreticulin in patients
      with O. volvulus infection. A total of 86% of the O. volvulus-infected
      individuals produced antibodies recognizing RAL1 rAg. Antibody reactivity to RAL1
      rAg in patient sera was confined primarily to the central and carboxyl-terminal
      parts of the molecule. No significant correlations were found to associate
      recognition of RAL1 rAg, or any particular portion thereof, with a particular
      disease state. Antibodies against RAL1 thus appear to be produced as a general
      immune reaction to O. volvulus infection and do not necessarily lead to a cross
      reacting response with the host protein. In contrast, 33% of the patient sera
      tested bound recombinant human calreticulin. All of these sera also recognized a
      polypeptide encompassing the carboxyl-terminal portion of the RAL1 rAg. These
      results suggest that recognition of an epitope encoded in the carboxyl-terminal
      portion of RAL1 is at least in part responsible for inducing a cross-reacting
      immune response to the host protein.

PMID- 7520418
TI  - T-cell-epitope mapping of the major secreted mycobacterial antigen Ag85A in
      tuberculosis and leprosy.
AB  - Lymphoproliferation and gamma interferon (IFN-gamma) secretion in response to 28
      overlapping 20-mer synthetic peptides covering the complete sequence of the
      mature (295-amino-acid) 85A component of the major secreted, fibronectin-binding
      antigen 85 complex from Mycobacterium tuberculosis and Mycobacterium bovis BCG
      (MTAg85A) was examined by using peripheral blood mononuclear cell (PBMC) cultures
      from healthy tuberculin- and lepromin-positive volunteers and from patients with
      tuberculosis and leprosy. Peptide recognition was largely promiscuous, with a
      variety of human leukocyte antigen haplotypes reacting to the same peptides. PBMC
      from all tuberculin-positive subjects reacted to Ag85, and the majority
      proliferated in response to peptide 6 (amino acids 51 to 70), peptides 13, 14,
      and 15 (amino acids 121 to 160), or peptides 20 and 21 (amino acids 191 to 220).
      PBMC from tuberculosis patients demonstrated a variable reactivity to Ag85 and
      its peptides, and the strongest proliferation was observed against peptide 7
      (amino acids 61 to 80). MTAg85A peptides were also recognized by PBMC from
      healthy lepromin-positive volunteers and paucibacillary leprosy patients (again
      in a promiscuous manner), but despite a 90% homology between the 85A proteins of
      M. leprae and M. tuberculosis, the peptides recognized were different. PBMC from
      lepromin-positive healthy contacts reacted against peptide 2 (amino acids 11 to
      30), peptide 5 (amino acids 41 to 60), and peptides 25 and 26 (amino acids 241 to
      270). PBMC from paucibacillary patients reacted preferentially against peptide 1
      (amino acids 1 to 20) and peptide 5. Multibacillary patients were not reactive to
      Ag85 or the MT85A peptides. IFN-gamma production was generally detected
      simultaneously with positive lymphoproliferative responses, although peptide 1
      mostly stimulated proliferation and peptides 27 and 28 mostly elicited an IFN
      gamma response. In conclusion, regions 41 to 80 and 241 to 295 demonstrated
      powerful and promiscuous T-cell-stimulatory properties, resulting in
      proliferative responses and IFN-gamma secretion, respectively, in the majority of
      reactive subjects tested in this study. These results could be of value in the
      development of a subunit vaccine for tuberculosis and leprosy.

PMID- 7520420
TI  - Mapping of bactericidal epitopes on the P2 porin protein of nontypeable
      Haemophilus influenzae.
AB  - The P2 porin protein is the major outer membrane protein of nontypeable
      Haemophilus influenzae and is a potential target of a protective immune response.
      Nine monoclonal antibodies (MAbs) to P2 were developed by immunizing mice with
      nontypeable H. influenzae whole organisms. Each MAb reacted exclusively with the
      homologous strain in a whole-cell immunodot assay demonstrating exquisite strain
      specificity. All nine MAbs recognized abundantly expressed surface-exposed
      epitopes on the intact bacterium by immunofluorescence and immunoelectron
      microscopy. Each MAb was bactericidal to the homologous strain in an in vitro
      complement-mediated killing assay. Immunoblot assay of cyanogen bromide cleavage
      products of purified P2 indicated that MAb 5F2 recognized the 10-kDa fragment,
      and the other eight MAbs recognized the 32-kDa fragment. Competitive ELISAs
      confirmed that 5F2 recognized an epitope that is different from the other eight
      MAbs. To further localize epitopes, MAbs 5F2 and 6G3 were studied in protein
      footprinting by using reversed-phase high-performance liquid chromatography.
      Three potential epitope-containing peptides which were reactive in an enzyme
      linked immunosorbent assay with both 5F2 and 6G3 were isolated. These peptides
      were identified by N-terminal amino acid sequence and localized to loops 5 and 8
      of the proposed model for P2. Fusion proteins consisting of glutathione S
      transferase fused with variable-length peptides from loops 5 and 8 were expressed
      in the pGEX-2T vector. Immunoblot assay of fusion peptides of loops 5 and 8
      confirmed that 5F2 recognized an epitope within residues 338 to 354 of loop 8;
      6G3 and the remaining MAbs recognized an epitope within residues 213 to 229 of
      loop 5. These studies indicate that nontypeable H. influenzae contains
      bactericidal epitopes which have been mapped to two different surface-exposed
      loops of the P2 molecule. These potentially protective epitopes are strain
      specific and abundantly expressed on the surface of the intact bacterium.

PMID- 7520423
TI  - Purification and characterization of the major antigen WI-1 from Blastomyces
      dermatitidis yeasts and immunological comparison with A antigen.
AB  - The lack of well-defined antigens from Blastomyces dermatitidis has hampered the
      ability to reliably diagnose human infection and study the immunobiology of
      blastomycosis. We recently discovered a novel surface protein on B. dermatitidis
      yeasts, designated WI-1, and demonstrated it to be a key antigenic target of
      humoral and cellular responses during infection. In the present article, we
      purified and characterized WI-1 and compared it immunologically with the only
      Blastomyces antigen commercially available, A antigen. WI-1 was purified by high
      performance liquid chromatography over a DEAE-cellulose column. It eluted from
      the column at a point on the salt gradient corresponding to 460 to 490 mM NaCl,
      reflecting its acidic pI of approximately equal to 5.2. Purified WI-1 had a
      molecular mass of 120 kDa and contained a large amount of cysteine (85 residues)
      and aromatic amino acids but undetectable carbohydrate. In contrast, A antigen
      had a molecular mass of 135 kDa and contained 37% carbohydrate. Immunological
      comparison of the two antigens showed that, when radiolabeled, WI-1 was more
      reactive with anti-Blastomyces antisera than A antigen but did not cross-react
      with anti-Histoplasma antisera. Proteinase digestion of WI-1 eliminated its
      recognition by anti-WI-1 and anti-Blastomyces antisera. Proteinase treatment of A
      antigen had no effect on its recognition by anti-Blastomyces or anti-Histoplasma
      antisera, but periodate treatment abolished recognition by anti-Histoplasma
      antisera, indicating that the cross-reactive determinant(s) of A antigen is
      displayed on the accompanying carbohydrate. In further studies, anti-WI-1
      antiserum reacted with A antigen and, conversely, anti-A antiserum and monoclonal
      antibodies (MAbs) reacted with WI-1, indicating a shared determinant on the two
      antigens. A recombinant 25-amino-acid repeat, recently cloned from WI-1 and found
      to be the major target of antibody recognition of WI-1, reacted strongly with
      anti-A antiserum and MAbs. In MAb competition tests, MAbs specific for the 25
      residue repeat abolished binding of anti-A antiserum to A antigen. In antigen
      inhibition tests, the recombinant repeat abolished binding of anti-A antiserum to
      A antigen. These results demonstrate that the repeat is the major site of
      antibody recognition of both WI-1 and A antigen and that the recombinant,
      nonglycosylated peptide could replace either native antigen in formatting better
      diagnostic tests for blastomycosis. Moreover, they suggest that producing fungal
      protein antigens as nonglycosylated peptides in a procaryotic expression system
      may circumvent problems of antigen cross-reactivity that are due to
      posttranslational modification.

PMID- 7520427
TI  - Vascular prosthetic bypass grafting in obstructive jaundice. Experimental and
      clinical perspectives.
AB  - The use of artificial grafts was proposed to facilitate the construction of
      palliative bilio-enteric bypass in proximal malignant biliary obstruction.
      Previous reported clinical experience is favorable. We present herein our
      preliminary clinical and experimental experience with Dacron and PTFE (Goretex)
      vascular grafts for the construction of bilio-duodenal bypass. Although our
      clinical results appear encouraging, the use of these prosthetic conduits is not
      supported by experimental data obtained in dogs.

PMID- 7520425
TI  - Carbohydrate-reactive, pore-forming outer membrane proteins of Aeromonas
      hydrophila.
AB  - Two outer membrane proteins of Aeromonas hydrophila A6, isolated in a one-step
      affinity chromatography process based on carbohydrate reactivity, were found to
      be pore-forming molecules in artificial planar bilayer membranes. These
      carbohydrate-reactive outer membrane proteins (CROMPs; M(r)s, 40,000 and 43,000)
      were subjected to amino acid analysis. The amino acid profiles for these two
      outer membrane proteins were almost identical. A partial protein sequence of a 14
      amino-acid fragment of the 40,000-Da protein revealed homology with outer
      membrane porins of Escherichia coli and A. hydrophila. CROMPs were compared with
      carbohydrate-reactive porins also extracted from outer membranes of A. hydrophila
      A6. These porins were isolated by using standard porin purification techniques
      (insolubility in 2% sodium dodecyl sulfate, solubility in 0.4 M NaCl, and
      Sephacryl S-200 gel filtration), and then Synsorb H type 2 affinity
      chromatography was done. The physical and functional properties of the
      carbohydrate-reactive porins and CROMPs were found to be identical. On the basis
      of pore-forming properties in planar lipid bilayers and channel inhibition with
      maltotriose solutions, a nonspecific, general diffusion porin and a LamB-like
      maltoporin were identified in both CROMP and carbohydrate-reactive porin
      preparations. To our knowledge, the use of carbohydrate reactivity to isolate
      channel-forming proteins from bacterial outer membranes has not been reported
      previously.

PMID- 7520426
TI  - Fibrosis adjacent to the anterior lens capsule after extracapsular cataract
      extraction.
AB  - Fibrosis, contraction and opacification of the posterior lens capsule after
      extracapsular cataract extraction, is a frequent complication following cataract
      surgery. In these cases, cellular proliferation occurs along an intact posterior
      capsule. We report a case of fibrosis adjacent to the anterior lens capsule,
      where cellular proliferations and collagen production completely sealed the
      anterior capsulotomy three months after a routine extracapsular cataract
      extraction with implantation of a posterior chamber lens. The fibrosis led to
      contraction of the remainder of the anterior capsule, significantly reducing
      vision. Examination of the excised material by light and electron microscopy, and
      immunohistochemistry, revealed cells with features compatible with fibrocytes
      that did not stain positive for cytokeratin. The cells were situated in a dense
      collagen matrix. An anterior capsulotomy that is too small prevents sufficient
      removal of lens epithelium, and may be a risk factor for this complication.

PMID- 7520424
TI  - Identification of antigenic epitopes in a surface protein antigen of
      Streptococcus mutans in humans.
AB  - The reactivities of antibodies in human serum and saliva to a cell surface
      protein antigen (PAc) of Streptococcus mutans and synthetic peptides covering the
      PAc molecule were examined. Both an enzyme-linked immunosorbent assay (ELISA) and
      Western blotting (immunoblotting) showed that all the serum samples from five
      adult subjects harboring serotype c S. mutans in their oral cavity reacted with
      recombinant PAc (rPAc). On the other hand, the serum from a 4-month-old infant
      did not react with rPAc in ELISA. The immunoglobulin A (IgA) antibodies in saliva
      samples from the five adult subjects reacted with rPAc. However, in saliva
      samples from these subjects, the titers of IgA antibody to rPAc did not correlate
      with the titers of serum antibody to the antigen. To map continuous antigenic
      epitopes in the PAc molecule, we synthesized 153 decapeptides covering the entire
      mature PAc molecule, 121 overlapping decapeptides covering the alanine-rich
      repeating region (A-region) of the PAc molecule, and 21 overlapping decapeptides
      covering the middle region (residues 824 to 853) according to multiple pin
      coupled peptide synthesis technology. Of 153 decapeptides covering the mature
      PAc, 27 decapeptides showed a strong reaction with the antibodies in serum from
      the adult subjects. The epitope-scanning patterns in the serum samples from these
      subjects were also very similar to each other. The antigenic epitope patterns in
      the saliva resembled those in the serum. However, the ELISA titers of salivary
      IgA antibodies to these decapeptides differed from the titers of the serum
      antibody. Of the 121 overlapping decapeptides covering the A-region, 27
      decapeptides showed a positive reaction with the antibodies in serum from the
      adult subjects. All of these 27 decapeptides had either one or two of the five
      common sequences YQAXL, NADAKA, VQKAN, NNAKNA, and IKKRNA. Six decapeptides of
      the 21 overlapping decapeptides covering the middle region reacted strongly with
      the serum antibodies from a high PAc responder, and each of the six decapeptides
      had one of the two common sequences KVTKEKP and VKPTAPTK. These epitopes might
      therefore be relevant to the humoral responses against the PAc protein during
      natural infection with S. mutans in humans.

PMID- 7520421
TI  - A 48-kilodalton Mycoplasma fermentans membrane protein induces cytokine secretion
      by human monocytes.
AB  - Mycoplasma fermentans is one of several Mycoplasma species that have been
      reported to stimulate tumor necrosis factor (TNF) secretion from monocytes. This
      activity has been associated primarily with the mycoplasma membrane fraction. In
      this article, we have characterized a membrane protein that stimulates TNF and
      interleukin 1 beta secretion. The TNF-releasing activity partitioned into the
      Triton X-114 detergent phase, suggesting that the molecules is hydrophobic. The
      secretion of TNF is elevated in the presence of serum, which suggests that a
      serum component may play a role in the interaction between this mycoplasma
      protein and monocytes. Treatment of monocytes with monoclonal anti-CD14 antibody
      had no effect on the levels of TNF-releasing activity. By using the monocyte
      Western blot (immunoblot) technique, we have determined the molecular mass of the
      active molecule to be 48 kDa. This molecule appears to be distinct from the
      recently described family of variable lipoproteins of M. fermentans. Mycoplasma
      particulate material treated with proteinase K lost all inducing activity,
      whereas lipoprotein lipase-treated samples retained some level of activity.

PMID- 7520428
TI  - Effect of copper and iron on neutrophil function and humoral immunity of
      gestating beef cattle.
AB  - Eighty gestating beef cattle were used to determine the effect of trace mineral
      salt mixtures containing copper (Cu) and iron (Fe) on selected immune functions
      and factors affecting copper bioavailability. Pastured cattle were randomly
      assigned to receive one of the following combinations of Cu and Fe in the free
      choice trace mineral salt: (1) 0 mg of Cu/0 mg of Fe/kg of trace mineral salt,
      (2) 1,600 mg of Cu (CuSO4)/3,000 mg of Fe/kg of trace mineral salt, (3) 1,600 mg
      of Cu (CuSO4)/0 mg of Fe/kg of trace mineral salt, and (4) 1,600 mg of Cu
      (CuCO3)/3,000 mg of Fe/kg of trace mineral salt. Total Cu/Fe consumption (from
      trace mineral salt) was 2/678, 193/1,050, 162/553, and 202/1,140 mg/head/d,
      respectively, for the 4 groups. After a 1-month period of acclimation and also on
      day 28 of the 36-day study, copper concentrations in serum were significantly (P
      < 0.05) lower in group 1 than in groups 3 and 4. Serum copper concentrations did
      not increase with time for any group, whereas hepatic copper concentrations
      increased significantly (P < 0.05) with time for all groups except group 1.
      Hepatic iron concentrations were similar among groups at the time of the initial
      and final hepatic biopsies on days 0 and 28, respectively. Hepatic iron
      concentrations increased significantly (P < 0.05) with time in groups 3 and 4.
      Humoral response to chicken gamma-globulin was high but did not differ among
      groups on any of the days analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520429
TI  - Generating hypotheses about the function of student problem behavior by observing
      teacher behavior.
AB  - We examined whether, as predicted by research on child effects, we could generate
      hypotheses about the function of student problem behavior by observing the amount
      of attention teachers provided to students. In the first phase of the study, we
      observed the amount of attention teachers distributed among small groups of
      students who exhibited problem behavior in individual or small-group
      instructional settings (problem behavior presumably maintained by attention or
      escape). Based on the amount of attention each student received, we generated
      hypotheses about the function of his or her problem behavior. In the second phase
      of the study, we determined the accuracy of these predictions by conducting a
      brief functional assessment with each student. Results confirmed that, for 14 of
      the 15 students, we were able to generate accurate hypotheses about the function
      of their problem behavior. These results suggest the potential efficacy of using
      the amount of attention teachers distribute among groups of students to generate
      empirically based hypotheses about the function of student problem behavior
      maintained by attention and/or escape. These results also illustrate the
      efficiency of this procedure; by observing teacher behavior, we were able to
      generate hypotheses about the function of problem behavior for several students
      at one time.

PMID- 7520422
TI  - Effect of lipopolysaccharide on mouse mast cell induction by a splenic cell
      culture system.
AB  - We have previously reported a method of mast cell induction by long-term culture
      of mouse spleen cells without using exogenous mast cell growth factor (Z.-Q. Hu,
      T. Yoshida, and T. Shimamura, J. Immunol. Methods 149:173, 1992). Supernatants
      recovered from the long-term cultures contain endogenous interleukin 3 and
      soluble stem cell factor. These were assessed by the capacity of the recovered
      supernatants to foster the growth of a mast cell growth factor-dependent cell
      line and by neutralizing antibodies. Besides the soluble factors, cell-to-cell
      contacts mediated by membrane stem cell factor on splenic stromal cells and c-Kit
      receptors on mast cells also affect mast cell induction. Different lots of fetal
      calf serum (FCS) were examined to determine a possible trigger for cytokine
      production. FCS can be divided into mast cell-inducible and noninducible sera by
      this process. However, not all FCS lots contain mast cell growth factor. The mast
      cell-inducible lots contain lipopolysaccharide (LPS) confirmed by a Limulus
      assay. Polymyxin B can neutralize the mast cell induction activity. Non-mast cell
      inducible FCS can be converted to inducible FCS by adding exogenous LPS. The
      results indicate that LPS as a trigger of cytokine production is responsible for
      mast cell induction.

PMID- 7520430
TI  - Emerging themes in the functional analysis of problem behavior.
AB  - The functional control of problem behavior is generally conceptualized as
      involving attention, escape, sensory reinforcement, and tangible factors. Our
      analytic tools have now reached a level of sophistication that makes possible
      consideration of several new, emerging themes in the area of functional analysis.
      First, we need to examine other functional properties of problem behavior
      involving social avoidance, biological reinforcement, and respondent conditioning
      factors. Second, we need to explore the role of context, including social factors
      such as group interactions, sequencing of tasks and activities, presence or
      absence of specific individuals, and crowding; as well as biological factors,
      such as physical illness, exercise, and drugs. Finally, we must consider the
      multidimensional character of assessment in naturalistic settings and the
      practical need for developing descriptive analytic procedures that complement and
      produce results that are congruent with those obtained from traditional
      functional analyses.

PMID- 7520432
TI  - Short-term daily exercise activity enhances endothelial NO synthesis in skeletal
      muscle arterioles of rats.
AB  - We aimed to test the hypothesis that as a consequence of short-term daily bouts
      of exercise the control of arteriolar smooth muscle by endothelium is altered.
      Rats ran on a treadmill once a day, 5 days/wk, for 2-4 wk (with gradually
      increasing intensity, up to 26 min at 22 m/min at a 1% grade by the beginning of
      the 3rd wk and up to 38 min at 28 m/min at a 2% grade by the beginning of the 4th
      wk) while a control group remained sedentary (SED). Cannulated and pressurized
      arterioles of rat gracilis muscle developed spontaneous myogenic tone, which was
      slightly enhanced in exercised (EX) compared with SED rat arterioles. At 80 mmHg
      pressure, the passive (Ca(2+)-free solution) and active diameters of SED and EX
      rat arterioles were 105.4 +/- 3.8 and 55.1 +/- 2.3 microns and 107.1 +/- 3.4 and
      50.2 +/- 2.2 microns, respectively. Dose-dependent dilations to sodium
      nitroprusside (10(-8)-10(-6) M) and constrictions to norepinephrine (10(-8)-10(
      6) M) were not affected in EX arterioles, whereas dilations to adenosine (10(-6)
      10(-4) M) were significantly reduced. In contrast, dose-dependent dilations to
      acetylcholine (ACh; 5 x 10(-9)-10(-7) M) and L-arginine [precursor of nitric
      oxide (NO); 10(-4)-10(-3) M] were significantly enhanced (by 33-78 and 57-75%,
      respectively) in arterioles of EX compared with those of SED rats. Responses of
      arterioles to sodium nitrite were not different in SED and EX groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7520431
TI  - Is nitric oxide involved in cutaneous vasodilation during body heating in humans?
AB  - The neurotransmitter responsible for neurogenic vasodilation in human skin during
      body heating is unknown. We sought to determine whether the vasodilating
      substance nitric oxide (NO) is involved in this phenomenon. Six subjects were
      heated for 50 min by use of a water-perfused suit while forearm blood flow (FBF)
      was measured with plethysmography and skin blood flow (SkBF) was measured by the
      laser-Doppler method in both arms. In one forearm, NG-monomethyl-L-arginine (L
      NMMA), an NO synthase blocker, was infused into the brachial artery. Bolus doses
      of L-NMMA (< or = 4 mg/min) for 5 min were given to blunt NO-mediated vasodilator
      responses to acetylcholine (ACh, 64 micrograms/min). A continuous infusion of L
      NMMA (< or = 1.0 mg/min) was used during body heating to maintain NO synthase
      blockade. In the forearm receiving L-NMMA, FBF was 1.8 +/- 0.3 ml.100 ml-1.min-1
      before drug infusion and rose to 9.5 +/- 1.3 ml.100 ml-1.min-1 with ACh. After L
      NMMA infusion, FBF was 1.3 +/- 0.2 ml.100 ml-1.min-1 and rose to 2.6 +/- 0.4
      ml.100 ml-1.min-1 with ACh (both P < 0.05 vs. pre-L-NMMA). Similar changes in
      SkBF were seen with ACh and L-NMMA, confirming that the drugs reached cutaneous
      vessels. With body heating, oral temperature increased by 1.2 degrees C, heart
      rate increased by 34 beats/min, and mean arterial pressure remained constant at
      approximately 75 mmHg. FBF in the treated forearm rose to 11.5 +/- 2.1 vs. 12.6
      +/- 1.7 ml.100 ml-1.min-1 in the control forearm (P > 0.05, control vs. treated
      response).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520433
TI  - Roles of calmodulin-dependent protein kinases and phosphatase in calcium
      dependent transcription of immediate early genes.
AB  - Recent studies indicate multiple mechanisms are involved in Ca2+ stimulation of
      gene expression. We have used cell-permeable, specific inhibitors of calmodulin
      dependent protein kinases (CaM kinases) and phosphatase (calcineurin) to
      investigate the involvement of these enzymes in transcriptional regulation of
      three immediate early genes in PC12 cells stimulated with A23187 or KCl.
      Preincubation of PC12 cells with the CaM kinase inhibitor KN-62 blocked
      autophosphorylation of CaM kinase II in response to stimulation by the Ca2+
      ionophore A23187. KN-62 treatment also resulted in a 60-70% inhibition of Ca(2+)
      dependent transcription of c-fos, NGFI-A (zif 268), and NGFI-B (nur 77) as
      assessed by either Northern or nuclear run-on analyses. Preincubation with the
      calcineurin inhibitors FK-506 or cyclosporin A strongly enhanced expression of
      NGFI-A and blocked transcription of NGFI-B, but it had no significant effect on
      Ca(2+)-stimulated transcription of c-fos. Both FK-506 and KN-62 were specific for
      Ca(2+)-stimulated transcription as neither effected transcription in response to
      forskolin or phorbol ester (12-O-tetradecanoylphorbol-13-acetate) treatment. This
      is the first report of CaM kinase and calcineurin involvement in transcriptional
      regulation of NGFI-A and NGFI-B. Activation of CaM kinases and calcineurin, in
      response to elevated intracellular Ca2+, would exert antagonistic effects on
      transcription of NGFI-A. Since inhibition of either the kinase or phosphatase
      decreased transcription of NGFI-B by 60-90%, this suggests that each enzyme is
      necessary but not sufficient for Ca2+ stimulation. These results indicate that
      CaM kinases and calcineurin can mediate broad and complex regulation of Ca(2+)
      stimulated gene expression.

PMID- 7520434
TI  - Mutation of a ligand binding domain of beta 3 integrin. Integral role of
      oxygenated residues in alpha IIb beta 3 (GPIIb-IIIa) receptor function.
AB  - A single amino acid substitution in beta 3 (Asp119 --> Tyr) abrogates the ligand
      binding function of beta 3 integrins and alters the divalent cation conformation
      of the platelet integrin alpha IIb beta 3 (GPIIb-IIIa). This aspartic acid
      residue resides within a conserved cluster of oxygenated residues that may
      provide ligands for the coordination of divalent cations. To assign function to
      the other oxygenated residues in this group (Ser121, Ser123, Asp126, Asp127, and
      Ser130), each of these amino acids in beta 3 was individually substituted by
      alanine. None of these amino acid substitutions altered heterodimer formation or
      surface expression. However, the substitutions had differential effects on
      receptor function. Substitution at positions Asp119 or Ser121 produced a complete
      loss of receptor function. Cells expressing these mutants failed to adhere to
      fibrinogen, failed to bind activation-independent ligand-mimetic peptides, and
      did not bind the ligand-mimetic mAb PAC1 following activation of the receptor.
      Similarly, cells expressing beta 3 with a substitution at Ser123 also failed to
      adhere to fibrinogen and did not bind RGD peptide or mAb PAC1. These cells did
      retain the capacity to bind an alpha IIb beta 3-specific, high affinity
      peptidomimetic, but occupancy did not induce the conformational change from
      resting to activated state observed following occupancy of the wild type
      receptor. Substitution at positions Asp126, Asp127, or Ser130 had no effect on
      ligand binding function. These data indicate that Asp119, along with Ser121 and
      Ser123, plays an integral role in the ligand binding function of alpha IIb beta
      3.

PMID- 7520435
TI  - Identification of integrin alpha 2 beta 1 as cell surface receptor for the
      carboxyl-terminal propeptide of type I procollagen.
AB  - The carboxyl-terminal propeptide of procollagen type I (CPP-I) plays a key role
      in the regulation of collagen fibrillogenesis. In addition, it has been reported
      that, after cleavage from procollagen, CPP-I exerts feedback control of collagen
      biosynthesis. To further elucidate the mechanisms involved in each of these
      processes, we have investigated the nature of cell surface receptors for CPP-I.
      CPP-I affinity chromatography, using detergent extracts of iodinated HT1080 cells
      and EDTA elution, resulted in the isolation of two polypeptides of molecular mass
      160 and 110 kDa. Since the migratory behavior of these polypeptides under
      nonreducing and reducing conditions was characteristic of a subset of integrin
      receptors, their reactivity with anti-integrin monoclonal antibodies was tested.
      Antibodies directed against the alpha 2 and beta 1 subunits specifically
      immunoprecipitated both CPP-I-binding polypeptides, indicating that the CPP-I
      receptor is the integrin alpha 2 beta 1. CPP-I was found to support the
      attachment and spreading of HT1080 cells, demonstrating that it can function as
      an adhesion protein. Two other approaches supported the identification of alpha 2
      beta 1 as the CPP-I receptor. First, anti-functional anti-integrin monoclonal
      antibodies directed against the alpha 2 and beta 1 subunits completely abrogated
      the adhesive activity of CPP-I and, second, highly purified CPP-I bound
      specifically to alpha 2 beta 1-containing integrin preparations in a solid-phase
      receptor-ligand binding assay. These findings have important implications for the
      function of fibrillar collagen carboxyl-terminal propeptides and for the role
      played by integrins in the regulation of cellular phenotype.

PMID- 7520437
TI  - The folding of bovine pancreatic trypsin inhibitor in the Escherichia coli
      periplasm.
AB  - PreOmpA-bovine pancreatic trypsin inhibitor (BPTI) (Goldenberg, D. P. (1988)
      Biochemistry 27, 2481-2489) was expressed in Escherichia coli, and the folding
      pathway of the mature protein in the periplasmic space was analyzed by pulse
      chase experiments. Folding intermediates were trapped with iodoacetamide,
      immunoprecipitated with antisera specific for either the reduced or the native
      protein, and resolved by electrophoresis. In vivo, native BPTI formed with a half
      life of 7 min which is 3-fold faster than the optimal in vitro folding rate in
      growth media supplemented with low molecular weight disulfides. The measured in
      vivo half-life includes the time required for translocation and processing by
      leader peptidase and therefore represents the lower limit for the actual folding
      rate in the cell. In addition to the native species, two-disulfide intermediates
      accumulated in the cell at appreciable levels and did not chase to the native
      species for at least 20 min. We found that the folding of BPTI in E. coli was
      absolutely dependent on DsbA, a protein which accelerates the formation of
      disulfide bonds in the periplasm. In a dsbA mutant strain, trace amounts of
      oxidized BPTI could be detected only in cultures grown under strongly oxidizing
      conditions. In wild-type cells, the addition of different concentrations of
      GSH/GSSG or oxidized dithiothreitol did not affect the kinetics of BPTI oxidation
      by DsbA. Finally, even though the folding of BPTI in vitro decreases by almost 10
      fold/unit pH decrease, folding in cells grown at pH 6.0 was only marginally
      slower than folding in cells grown at neutral pH, despite the fact that the pH of
      the periplasmic space varies in response to the extracellular fluid.

PMID- 7520436
TI  - Expression cloning of SR-BI, a CD36-related class B scavenger receptor.
AB  - Scavenger receptors are integral membrane proteins that mediate the endocytosis
      of modified lipoproteins. The first of these to be purified and cloned were the
      type I and II macrophage scavenger receptors (SR-AI and SR-AII; class A scavenger
      receptors). Subsequently, the cell surface protein CD36 was shown to bind
      oxidized low density lipoprotein (oxidized LDL). From a Chinese hamster ovary
      (CHO) cell variant we have cloned by expression the cDNA for a new member of the
      CD36 family of membrane proteins, SR-BI, whose predicted protein sequence of 509
      amino acids is approximately 30% identical to those of the four previously
      identified family members. Both SR-BI and CD36 displayed high affinity binding
      for acetylated LDL with an apparent dissociation constant on the order of
      approximately 5 micrograms of protein/ml. The ligand binding specificities of
      CD36 and SR-BI, determined by direct binding or competition assays, were similar,
      but not identical; both bind modified proteins (acetylated LDL, oxidized LDL,
      maleylated bovine serum albumin), but not the broad array of other polyanions
      (e.g. fucoidin, polyguanosinic acid, carrageenan) which are ligands of the class
      A receptors. Thus, SR-BI and CD36 define a second class of scavenger receptors,
      designated class B. Native LDL, which does not bind to either class A receptors
      or CD36, unexpectedly bound with high affinity to SR-BI. Northern blot analysis
      of murine tissues showed that SR-BI was most abundantly expressed in fat and was
      present at moderate levels in lung and liver. Furthermore, SR-BI mRNA expression
      was induced upon differentiation of 3T3-L1 cells into adipocytes. Thus, the
      tissue distribution of expression and ligand binding properties of SR-BI raise
      the possibility that this cell surface receptor may play an important role in
      lipid metabolism.

PMID- 7520438
TI  - Inhibition of calcineurin by a novel FK-506-binding protein.
AB  - FK-506, a potent immunosuppressive drug, acts during the commitment phase of T
      lymphocyte activation to block a subset of calcium-associated events necessary
      for transcription of certain early lymphokine genes. The drug binds to an
      abundant, cytosolic 11.8-kDa protein termed the FK-506-binding protein (FKBP12).
      The FKBP12.FK-506 complex inhibits calcineurin, a calcium-dependent phosphatase
      that is a component of the signal transduction pathway leading to early
      lymphokine gene transcription. FKBP12 is one member of a growing gene family.
      Prior to this report, all other FKBP family members had been irrelevant to the
      mechanism of action of FK-506 because no other FKBP.FK-506 complexes were able to
      bind and inhibit calcineurin. Here, we report the purification and
      characterization of a novel FK-506-binding protein, FKBP12.6. Having 85% amino
      acid sequence identity to FKBP12, FKBP12.6 is, among the FKBPs, most closely
      related to FKBP12. When complexed with FK-506, FKBP12.6 binds to and inhibits
      calcineurin, making it only the second FKBP discovered thus far to do so. The
      ability to inhibit calcineurin establishes the potential relevance of FKBP12.6 to
      the immunosuppressive or toxic side effects of FK-506.

PMID- 7520439
TI  - Characterization of ryudocan glycosaminoglycan acceptor sites.
AB  - The specificity of the glycosaminoglycan (GAG) acceptor sites of ryudocan was
      examined by stably expressing epitope-tagged ryudocan cDNA constructs in mouse L
      cells, which normally produce this proteoglycan. Immunopurified ryudocan was
      glycanated with both heparan sulfate (HS) and chondroitin sulfate (CS). The
      attachment of GAGs to ryudocan was prevented by creating Ser-->Thr mutations in
      all possible combinations at positions 44, 65, and 67. The resulting ryudocan of
      exogenous origin was immunopurified and evaluated with regard to attached GAG
      chains. The data reveal that ryudocan possesses three functional GAG attachment
      sites, that the sites are always occupied with GAG chains, and that each site is
      capable of bearing either HS or CS. The sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis patterns of GAG lyase digests of intact ryudocan reveal the
      production of the following multiple isoforms: pure HS-ryudocan, various HS/CS
      hybrids, and pure CS-ryudocan. The data suggest that the occupancy bias of each
      site for HS or CS is slight and that each site functions in a relatively
      independent fashion. The GAG lyase analysis of partially purified L cell
      proteoglycans shows two pure CS-homoglycans with core proteins of M(r) = 130,000
      and 52,000, respectively. A similar analysis of immunopurified L cell glypican
      demonstrates that this species only exists as a pure HS-homoglycan. The
      production of pure homoglycans by this clonal cell line strongly suggests that
      the functional promiscuity of GAG attachment sites of ryudocan must be encoded in
      the core protein structure. This property of ryudocan is not peculiar to L cells,
      as ryudocan synthesized by early passage human endothelial cells also bears both
      HS and CS. The production of multiple isoforms of ryudocan may serve to expand
      the functional versatility of this cell surface component and allow it to
      participate in many different biologic processes.

PMID- 7520441
TI  - Human kit ligand (stem cell factor) modulates platelet activation in vitro.
AB  - The human stem cell factor (SCF), also termed c-Kit ligand (KL), is a
      hematopoietic growth factor produced by mesenchymal cells that induces
      proliferation of bone marrow progenitor cells, megakaryocytes, and mast cells via
      interaction with c-Kit, its cognate receptor. Expression of the c-kit gene was
      identified in human platelets by the polymerase chain reaction technique. The
      presence of the c-Kit receptor was demonstrated by the specific binding of 125I
      KL/SCF to ADP-stimulated platelets. The identity of the c-Kit protein was
      confirmed by immunoreactivity with an anti-c-Kit-specific antibody and by its
      characterization as a phosphotyrosine-containing protein. Under constitutive
      conditions, c-Kit was found to be tyrosine-phosphorylated and was associated with
      a 85-kDa phosphoprotein that could be a fragment of phosphatidylinositol 3
      kinase. These data indicate the presence of a new platelet surface molecule that
      could function in platelet activation. We demonstrate that the secondary wave of
      platelet aggregation and serotonin secretion induced by epinephrine and ADP, but
      not by the thromboxane analog U46619, was augmented by KL/SCF. The effect of
      KL/SCF on epinephrine/ADP-induced platelet activation appeared to be mediated in
      part through the thromboxane pathway. These data suggest that KL/SCF could
      modulate hemostasis via interaction with platelets, particularly in conditions
      where mesenchymal cells are exposed to circulating blood elements, such as in
      wound healing or atherosclerosis.

PMID- 7520440
TI  - Nitric oxide inhibits neuronal nitric oxide synthase by interacting with the heme
      prosthetic group. Role of tetrahydrobiopterin in modulating the inhibitory action
      of nitric oxide.
AB  - The objective of this study was to elucidate the mechanism by which nitric oxide
      (NO) inhibits NO synthase. Previous studies revealed that NO inhibits unpurified
      preparations of NO synthase. In the present study, the mechanism by which NO
      inhibits purified neuronal NO synthase from rat cerebellum was examined. The rate
      of L-citrulline formation from L-arginine was non-linear despite the presence of
      excess substrate and cofactors and was further inhibited by 30% by 200 units/ml
      superoxide dismutase. In contrast, 30 microM oxyhemoglobin increased NO synthase
      activity by 2-fold and made the reaction rate linear. These observations were
      consistent with the hypothesis that enzymatically generated NO inhibits NO
      synthase activity. Exogenous NO (0.1-10 microM) (but not NO2, nitrite, or
      nitrate) also inhibited NO synthase, and enzyme inhibition was not competitive
      with L-arginine. NO synthase inhibition by NO and other heme ligands supports the
      view that heme is involved in the catalytic activity of NO synthase.
      Oxyhemoglobin prevented but could not reverse enzyme inhibition by NO. NO
      synthase inhibition by NO was markedly diminished and reversed, however, by
      tetrahydrobiopterin (50 microM) or a tetrahydrobiopterin-regenerating system, and
      the latter made the reaction rate linear. In contrast, NO synthase inhibition by
      NO was markedly enhanced by heme oxidants (10 microM methylene blue; 3 microM
      ferricyanide), and these oxidants directly inhibited NO synthase activity. These
      observations suggest that NO interacts with enzyme-bound ferric heme to inhibit
      NO synthase activity. In support of this view, NO inhibited enzyme activity in
      the absence of turnover, when the heme iron is in the ferric state, and this
      inhibition was reversed by tetrahydrobiopterin. Therefore, the oxidation state of
      heme iron appears to be one important determinant for the inhibitory action of
      NO, and tetrahydrobiopterin may increase NO synthase activity by diminishing the
      inhibitory action of NO.

PMID- 7520442
TI  - An active recombinant p15 RNase H domain is functionally distinct from the RNase
      H domain associated with human immunodeficiency virus type 1 reverse
      transcriptase.
AB  - An active p15 RNase H domain, consisting of amino acids 427-560 of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and a
      genetically engineered penta-histidine N-terminal affinity tag, was expressed in
      Escherichia coli and purified to apparent homogeneity by immobilized metal
      affinity chromatography. The purified p15 RNase H domain exhibited no substrate
      preference for [3H]poly(rG).poly(dC) compared to [3H]poly(rA).poly(dT), in
      contrast with the HIV-1 RT-associated RNase H, which showed a 30-fold preference
      for the former substrate. Unlike the HIV-1 RT-associated RNase H, when challenged
      with unlabeled substrate, the recombinant p15 RNase H domain was relatively
      nonprocessive in RNA degradative activity of the [3H]poly(rA).poly(dT) duplex.
      Kinetic studies using p15 RNase H showed substrate inhibition with an apparent
      K(i) value of 0.12 micron for the [3H]poly(rA).poly(dT) hybrid. Substrate
      inhibition was not observed for the HIV-1 RT-associated RNase H. The results show
      that the isolated p15 HIV-1 RNase H domain is functionally distinct from the
      recombinant HIV-1 RT-associated RNase H.

PMID- 7520443
TI  - Molecular and functional characterization of the non-isopeptide-selective ETB
      receptor in endothelial cells. Receptor coupling to nitric oxide synthase.
AB  - There is accumulating evidence that endothelial cells express a non-isopeptide
      selective endothelin (ET) receptor, ETB, which may be responsible for ET-1
      induced transient vasorelaxation. The purpose of the present study was to seek
      direct evidence for ETB receptor expression in human umbilical vein endothelial
      cells (HUVEC) and to characterize its functional role in HUVEC and in Chinese
      hamster ovary cells stably transfected with ETB receptor cDNA (CHO-ETB). Reverse
      polymerase chain reaction using HUVEC total RNA and ETB receptor-specific
      oligonucleotide primers firmly demonstrated the presence of an endogenous
      transcript of the appropriate molecular size. Next, a biotinylated ligand
      specifically recognizing the ETB receptor, IRL-1620, was synthesized, and
      immunocytochemical mapping of binding sites was performed in CHO-ETB cells.
      Specific binding of biotinylated IRL-1620 was evident in CHO-ETB cells,
      confirming appropriate cell surface receptor expression. Continuous nitric oxide
      (NO) monitoring with NO-selective electrode revealed a dose-dependent ET-1
      stimulation of NO production by HUVEC. Stable transfection of CHO-ETB cells with
      endothelial nitric oxide synthase (NOS), but not mock-transfection, imparted
      responsiveness to ET-1 similar to that for HUVEC and was characterized by the
      immediate release of NO. Protein tyrosine kinase-dependent and calcium-calmodulin
      dependent pathways were involved in ET-1-induced activation of the constitutive
      NOS in CHO-ETB/NOS cells, but coupling of the receptor to the enzyme in HUVEC
      appeared to be predominantly protein tyrosine kinase-dependent. Although
      sufficient, calcium/calmodulin system was not an obligatory prerequisite for the
      ET-1-induced activation of NOS in HUVEC. In conclusion, using two cell systems,
      we demonstrated that the ETB receptor is functionally coupled to NOS and
      coordinates the generation of NO via a tyrosine kinase-dependent and a
      calcium/calmodulin-dependent pathway.

PMID- 7520444
TI  - Modulation of Kit/stem cell factor receptor-induced signaling by protein kinase
      C.
AB  - The Kit/stem cell factor receptor (Kit/SCF-R) is a transmembrane tyrosine kinase
      receptor of importance for the normal development of hemopoietic cells,
      melanoblasts, and germ cells. We recently reported that protein kinase C (PKC) is
      involved in a negative feedback loop regulating the Kit/SCF-R by direct
      phosphorylation on serine residues in the receptor. Inhibition of PKC led to
      increased SCF-induced tyrosine kinase activity and mitogenicity, but PKC was
      necessary for SCF-induced motility. In this report we have further examined the
      modulatory role of PKC on SCF-induced signaling. The ligand-activated Kit/SCF-R
      associated weakly with GRB2 and induced only little tyrosine phosphorylation of
      phospholipase C-gamma in porcine aortic endothelial cells transfected with
      Kit/SCF-R. In contrast, the SCF-stimulated Kit/SCF-R associated efficiently with,
      and induced tyrosine phosphorylation of, the p85 alpha regulatory subunit of
      phosphatidyl inositide-3'-kinase (PI-3'-kinase). Both receptor association and
      tyrosine phosphorylation of p85 alpha were increased after inhibition of PKC,
      while its serine phosphorylation was decreased. Concomitantly, the specific
      activity of receptor-associated PI-3'-kinase activity was increased. Inhibition
      of PI-3'-kinase with wortmannin inhibited SCF-induced mitogenicity. SCF-induced
      phosphorylation of Raf-1 and activation of ERK2 still occurred after PKC
      inhibition but was not increased. In conclusion, SCF-induced PI-3'-kinase
      activation paralleled the increased SCF-induced mitogenicity after inhibition of
      PKC.

PMID- 7520445
TI  - Quenching of the tyrosyl free radical of ribonucleotide reductase by nitric
      oxide. Relationship to cytostasis induced in tumor cells by cytotoxic
      macrophages.
AB  - Nitric oxide (NO) synthesized by macrophages inhibits tumor cell replication. NO
      also inhibits ribonucleotide reductase, an enzyme essential for DNA synthesis,
      probably by quenching the catalytically active tyrosyl free radical of its R2
      subunit. The role of this inhibition in NO-mediated cytostasis was thus
      evaluated. After a 4-h coculture with macrophages, quenching of the radical was
      demonstrated by electron paramagnetic resonance spectroscopy in transfected L1210
      R2 cells over-expressing the R2 protein. Pronounced cytostasis was simultaneously
      observed. A NO synthase inhibitor greatly reduced both phenomena. Target cells
      withdrawn from macrophages partially recovered from cytostasis and radical loss
      within 90 min. Deoxyribonucleosides added to by-pass ribonucleotide reductase
      inhibition efficiently reversed cytostasis of K-562 cells. After a 24-h
      coculture, the quenched tyrosyl radical still reappeared in L1210-R2 cells
      withdrawn from macrophages, but DNA synthesis did not resume. Moreover,
      deoxyribonucleosides marginally reversed overnight cytostasis of K-562 cells
      mediated by macrophages but were efficient against cytostasis induced by
      hydroxyurea, a ribonucleotide reductase inhibitor. Autocrine cytostasis observed
      early in TA3-H2 cells committed to produce NO was closely correlated with
      quenching of the tyrosyl radical but not with formation of dinitrosyl-iron
      complexes. We thus propose that NO-dependent cytostasis begins with a rapid and
      reversible inhibition of ribonucleotide reductase, progressively reinforced by
      other, long-lasting antiproliferative effects.

PMID- 7520446
TI  - Interactions of Escherichia coli endonuclease IV and exonuclease III with abasic
      sites in DNA.
AB  - Duplex oligodeoxynucleotides with synthetic analogs of abasic sites were used to
      study the specificity of the abasic endonucleases of Escherichia coli. The
      apparent Km values of exonuclease III for the tetrahydrofuranyl, propanyl, and
      deoxyribosyl substrates varied only somewhat (20-140 nM) in either Mg2+ or Ca2+
      and were similar to those for endonuclease IV. In Mg2+, exonuclease III had a
      turnover number 4-13-fold higher than measured for endonuclease IV (ranging 5.6
      18 min-1), but was lowered in Ca2+ to values similar to those for endonuclease
      IV. The rate of cleavage of tetrahydrofuranyl (F) substrate by both enzymes was
      unaffected by the base in the opposite strand or its replacement by a
      tetrahydrofuranyl moiety. A C:C mismatch on the 5' but not the 3' side of F
      strongly inhibited cleavage by exonuclease III in Ca2+, while mismatches on both
      sides were required to diminish endonuclease IV cleavage significantly. A
      phosphorothioate ester linked 5' to the tetrahydrofuranyl moiety inhibited both
      enzymes, with the Rp stereoisomer most effective. Endonuclease IV bound stably to
      duplex substrates containing the Rp phosphorothioate in the presence of poly(dI
      dC). Although the apurinic/apyrimidinic-cleaving activities of endonuclease IV
      and exonuclease III have some common features they also differ in their specific
      interactions with DNA containing abasic sites.

PMID- 7520447
TI  - Lysosomes can fuse with a late endosomal compartment in a cell-free system from
      rat liver.
AB  - The passage of pulse doses of asialoglycoproteins through the endosomal
      compartments of rat liver hepatocytes was studied by subcellular fractionation
      and EM. The kinetics of disappearance of radiolabeled asialofetuin from light
      endosomes prepared on Ficoll gradients were the same as the kinetics of
      disappearance of asialoorosomucoid-horse radish peroxidase reaction products from
      intracellular membrane-bound structures in the blood sinusoidal regions of
      hepatocytes. The light endosomes were therefore identifiable as being derived
      from the peripheral early endosome compartment. In contrast, the labeling of
      dense endosomes from the middle of the Ficoll gradient correlated with EM showing
      large numbers of reaction product-containing structures in the nonsinusoidal
      parts of the hepatocyte. In cell-free, postmitochondrial supernatants, we have
      previously observed that dense endosomes, but not light endosomes, interact with
      lysosomes. Cell-free interaction between isolated dense endosomes and lysosomes
      has now been reconstituted and analyzed in three ways: by transfer of
      radiolabeled ligand from endosomal to lysosomal densities, by a fluorescence
      dequenching assay which can indicate membrane fusion, and by measurement of
      content mixing. Maximum transfer of radiolabel to lysosomal densities required
      ATP and GTP plus cytosolic components, including N-ethylmaleimide-sensitive
      factor(s). Dense endosomes incubated in the absence of added lysosomes did not
      mature into vesicles of lysosomal density. Content mixing, and hence fusion,
      between endosomes and lysosomes was maximal in the presence of cytosol and ATP
      and also showed inhibition by N-ethyl-maleimide. Thus, we have demonstrated that
      a fusion step is involved in the transfer of radiolabeled ligand from an isolated
      endosome fraction derived from the nonsinusoidal regions of the hepatocyte to
      preexisting lysosomes in a cell-free system.

PMID- 7520450
TI  - Widespread attenuation of the cerebrovascular reactivity to hypercapnia following
      inhibition of nitric oxide synthase in the conscious rat.
AB  - Despite the increasing number of publications devoted to the cerebrovascular role
      of NO, its precise influence in awake animals is still poorly characterized. The
      effect of nitric oxide synthase (NOS) inhibition on the cerebrovascular CO2
      reactivity was therefore studied in conscious rats. Regional CBF was measured
      using the [14C]iodoantipyrine technique and brain tissue sampling. The CO2
      reactivity was determined 60 min after administration of 30 mg kg-1 N omega-nitro
      L-arginine methyl ester (L-NAME). Blockade of NOS by L-NAME significantly
      decreased CBF in all 11 brain regions studied (-17 to -49%) and increased
      arterial pressure from 117 +/- 12 to 147 +/- 11 mn Hg. In control conditions, CO2
      responsiveness ranged from 1.3 +/- 0.4 in the hypophysis to 6.4 +/- 0.6 ml 100 g
      1 min-1 mm Hg-1 in the parietal cortex. Following L-NAME injection, the
      reactivity to hypercapnia was significantly attenuated in all structures, the
      magnitude of the reduction ranging from 57% in the medulla to 74% in the
      cerebellum. This result shows that NO is an important mediator of the hypercapnic
      vasodilation in the conscious rat.

PMID- 7520448
TI  - Induction of tyrosine phosphorylation during ICAM-3 and LFA-1-mediated
      intercellular adhesion, and its regulation by the CD45 tyrosine phosphatase.
AB  - Intercellular adhesion molecule (ICAM)-3, a recently described counter-receptor
      for the lymphocyte function-associated antigen (LFA)-1 integrin, appears to play
      an important role in the initial phase of immune response. We have previously
      described the involvement of ICAM-3 in the regulation of LFA-1/ICAM-1-dependent
      cell-cell interaction of T lymphoblasts. In this study, we further investigated
      the functional role of ICAM-3 in other leukocyte cell-cell interactions as well
      as the molecular mechanisms regulating these processes. We have found that ICAM-3
      is also able to mediate LFA-1/ICAM-1-independent cell aggregation of the leukemic
      JM T cell line and the LFA-1/CD18-deficient HAFSA B cell line. The ICAM-3-induced
      cell aggregation of JM and HAFSA cells was not affected by the addition of
      blocking mAb specific for a number of cell adhesion molecules such as CD1
      1a/CD18, ICAM-1 (CD54), CD2, LFA-3 (CD58), very late antigen alpha 4 (CD49d), and
      very late antigen beta 1 (CD29). Interestingly, some mAb against the leukocyte
      tyrosine phosphatase CD45 were able to inhibit this interaction. Moreover, they
      also prevented the aggregation induced on JM T cells by the proaggregatory anti
      LFA-1 alpha NKI-L16 mAb. In addition, inhibitors of tyrosine kinase activity also
      abolished ICAM-3 and LFA-1-mediated cell aggregation. The induction of tyrosine
      phosphorylation through ICAM-3 and LFA-1 antigens was studied by
      immunofluorescence, and it was found that tyrosine-phosphorylated proteins were
      preferentially located at intercellular boundaries upon the induction of cell
      aggregation by either anti-ICAM-3 or anti-LFA-1 alpha mAb. Western blot analysis
      revealed that the engagement of ICAM-3 or LFA-1 with activating mAb enhanced
      tyrosine phosphorylation of polypeptides of 125, 70, and 38 kD on JM cells. This
      phenomenon was inhibited by preincubation of JM cells with those anti-CD45 mAb
      that prevented cell aggregation. Altogether these results indicate that CD45
      tyrosine phosphatase plays a relevant role in the regulation of both
      intracellular signaling and cell adhesion induced through ICAM-3 and beta 2
      integrins.

PMID- 7520449
TI  - Altered localization and cytoplasmic domain-binding properties of tyrosine
      phosphorylated beta 1 integrin.
AB  - We describe a novel approach to study tyrosine-phosphorylated (PY) integrins in
      cells transformed by virally encoded tyrosine kinases. We have synthesized a
      peptide (PY beta 1 peptide) that represents a portion of the cytoplasmic domain
      of the beta 1 integrin subunit and is phosphorylated on the tyrosine residue
      known to be the target of oncogenic tyrosine kinases. Antibodies prepared against
      the PY beta 1 peptide, after removal of cross-reacting antibodies by absorption
      and affinity purification, recognized the PY beta 1 peptide and the tyrosine
      phosphorylated form of the intact beta 1 subunit, but did not bind the
      nonphosphorylated beta 1 peptide, the nonphosphorylated beta 1 subunit or other
      unrelated tyrosine-phosphorylated proteins. The anti-PY beta 1 antibodies labeled
      the podosomes of Rous sarcoma virus-transformed fibroblasts, but did not
      detectably stain nontransformed fibroblasts. The localization of the tyrosine
      phosphorylated beta 1 subunits appeared distinct from that of the beta 1 subunit.
      Adhesion plaques were stained by the anti-beta 1 subunit antibodies in Rous
      sarcoma virus-transformed fibroblasts plated on fibronectin, whereas neither
      podosomes nor adhesion plaques were labeled on vitronectin or on uncoated plates.
      Anti-phosphotyrosine antibodies labeled podosomes, adhesion plaques and cell-cell
      boundaries regardless of the substratum. One of the SH2 domains of the p85
      subunit of phosphatidylinositol-3-kinase bound to the PY beta 1 peptide, but not
      to the non-phosphorylated beta 1 cytoplasmic peptide. Other SH2 domains did not
      bind to the PY beta 1 peptide. These results show that the phosphorylated form of
      the beta 1 integrin subunit is detected in a different subcellular localization
      than the nonphosphorylated form and suggest that the phosphorylation on tyrosine
      of the beta 1 subunit cytoplasmic domain may affect cellular signaling pathways.

PMID- 7520451
TI  - Augmentation of blood flow through cerebral collaterals by inhibition of nitric
      oxide synthase.
AB  - We examined the influence of nitric oxide (NO) on normal and collateral cerebral
      blood flow after occlusion of the middle cerebral artery (MCA). Effects of NG
      nitro-L-arginine (nitroarginine), an inhibitor of NO synthase, were examined
      during normotension and hypotension (arterial pressure, 50 mm Hg) in 49
      anesthetized dogs. Following a craniotomy, a branch of the MCA was cannulated,
      and collateral-dependent tissue was identified using the shadow-flow technique.
      Regional cerebral blood flow was measured with microspheres, and pial artery
      pressure was measured with a micropipette. Intravenous nitroarginine reduced
      blood flow to normal cerebrum by approximately 40% (p < 0.05) during normotension
      and hypotension, with aortic pressure maintained constant after nitroarginine
      administration. Injection of nitroarginine during hypotension, without control of
      pressor effects, increased aortic and pial artery pressure approximately twofold.
      Concurrently, blood flow to normal cerebrum decreased (p < 0.05), while flow to
      collateral-dependent cerebrum increased (p < 0.05). Phenylephrine was infused
      during hypotension to increase arterial pressure to values similar to those
      achieved following nitroarginine. Blood flow to collateral-dependent cerebrum
      increased (p < 0.05), but flow to normal cerebrum was not altered during infusion
      of phenylephrine. Thus, inhibition of NO synthase during hypotension increases
      arterial pressure, decreases blood flow to normal cerebrum, and increases blood
      flow to collateral-dependent cerebrum. Phenylephrine also increases perfusion
      pressure and blood flow to collateral-dependent cerebrum, but in contrast to
      nitroarginine, it does not redistribute blood flow from normal cerebrum.

PMID- 7520452
TI  - Microglial response to transient focal cerebral ischemia: an immunocytochemical
      study on the rat cerebral cortex using anti-phosphotyrosine antibody.
AB  - Microglial response to transient focal ischemia was examined using an
      immunohistochemical method with a monoclonal antibody to phosphotyrosine (P-Tyr).
      For this purpose, a rat model of reversible middle cerebral artery occlusion for
      1 h was used. Compared with results in the noninsulted hemisphere, there was a
      significant increase in P-Tyr immunolabeling of the microglia in the insulted
      cerebral cortex 3 h postreperfusion. This microglial reaction progressed up to 24
      h after ischemic insult. In the affected cerebral cortex, morphological changes
      of the microglial positive for P-Tyr were also observed, with shortened and
      thickened processes, enlarged cell bodies, and ameboid features. Cell density
      analysis did not show any apparent change in number of P-Tyr-positive microglia
      in the insulted cortex at 6, 12, and 24 h after reperfusion, suggesting that the
      cells with increased P-Tyr immunoreactivity were resident microglia. The present
      findings suggest that signal transduction mediated by tyrosine phosphorylation is
      involved in the microglial response to ischemic injury in the rat cerebral
      cortex.

PMID- 7520453
TI  - Cytokine-mediated activation of cultured CNS microvessels: a system for examining
      antigenic modulation of CNS endothelial cells, and evidence for long-term
      expression of the adhesion protein E-selectin.
AB  - Much of what is known of endothelial responses to cytokines has been derived from
      in vitro studies using cultured human umbilical vein endothelial cells (EC). Less
      is known of CNS EC responses and whether intact endothelium responds similarly to
      cultured cells. We have used techniques by which rat CNS microvessels can be
      isolated, then cultured in vitro, to study the response of intact endothelium to
      activation with cytokines. These microvessels are composed of viable EC and
      perivascular cells, predominantly pericytes. Expression of EC activation antigens
      in multicellular systems such as cultured microvessels can be assessed
      quantitatively using immunofluorescence laser cytometry. Interferon gamma
      increased immunologically reactive major histocompatibility complex class II
      antigens (< 300 to 2,398 +/- 225 average fluorescence intensity), while tumor
      necrosis factor alpha induced an increase in vascular cell adhesion molecule-1
      (2,167 +/- 171) and E-selectin (1,628 +/- 315). CNS EC appeared to respond
      similarly to cultured EC with the exception that E-selectin expression was not
      transiently expressed but was maintained by microvessel EC for 24 and 48 h.
      Cultured CNS microvessels provide a good system for studying EC activation.

PMID- 7520454
TI  - Psychiatric morbidity in school-age children with congenital human
      immunodeficiency virus infection: a pilot study.
AB  - This study examined the relationship between human immunodeficiency virus (HIV)
      infection and psychiatric morbidity within the context of prenatal drug exposure.
      Twenty-six HIV-infected, 14 seroreverted, and 20 control (non-HIV-exposed)
      children were studied; the sample consisted of nonreferred children living in
      foster placement who had been exposed to maternal drug addiction. Each child
      received a psychiatric diagnostic evaluation which included completion by the
      caretaker of a structured diagnostic interview and a behavior checklist on the
      child as well as a child self-report on a pictorial interview. Age, ethnicity,
      and IQ were controlled in the analyses because of group differences. There were
      high rates of behavioral and psychiatric morbidity, especially with respect to
      disruptive behavior disorders, in this sample of school-age children with HIV
      infection, but similarly high rates were found in the seroreverted and non-HIV
      exposed children. There was some suggestion that the HIV-infected children were
      experiencing higher levels of subjective distress than either the nonexposed or
      seroreverted children. The possible relevance of drug exposure to the behavioral
      outcomes observed here is discussed, as well as the importance of using age
      appropriate materials to elicit subjective distress in HIV-infected school-age
      children. Clinical implications and directions for further research are
      discussed.

PMID- 7520456
TI  - GABAergic projection from the intercalated cell masses of the amygdala to the
      basal forebrain in cats.
AB  - The intercalated cell masses (ICMs) are dense clusters of small GABAergic cells
      interposed between the basolateral and centromedial nuclear groups of the
      amygdala. Until now, the ICMs have been largely ignored in anatomical studies of
      the amygdaloid complex. Thus, this study was undertaken to identify some of their
      targets by means of tract-tracing methods combined with immunohistochemical
      techniques. Wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP)
      was injected into numerous cortical areas and dorsal thalamic nuclei, in the
      anterior commissure and/or stria terminalis nuclei, and in the caudate nucleus,
      as well as into lateral and preoptic hypothalamic areas. Very few retrogradely
      labeled cells were seen in the ICMs following these injections. In contrast,
      massive retrograde labeling was found in the rostral groups of ICMs after WGA-HRP
      injections involving the substantia innominata and horizontal limb of the
      diagonal band. Furthermore, these retrogradely labeled intercalated cells were
      also GABA-immunoreactive. Results of iontophoretic injections of Phaseolus
      vulgaris-leucoagglutinin (PHA-L) in the rostral ICMs confirmed that they
      contribute a massive projection to the entire extent of the substantia innominata
      and horizontal limb of the diagonal band. Electron microscopic observations of
      ultrathin sections prepared for postembedding GABA or glutamate
      immunocytochemistry revealed that the ICM terminals labeled with PHA-L displayed
      GABA, but not glutamate immunoreactivity, and formed symmetric synapses with
      dendritic profiles. The present findings constitute the first direct
      demonstration of an amygdalofugal GABAergic projection to the basal forebrain.
      Considering that the basal forebrain contains a group of cholinergic and
      GABAergic neurons collectively projecting to the entire cortical mantle, this
      GABAergic projection of the ICMs could allow the amygdaloid complex to influence
      the activity of widespread cortical regions to which it is not directly
      connected, at least in the cat.

PMID- 7520455
TI  - Epitope analysis of antibodies recognising the cell proliferation associated
      nuclear antigen previously defined by the antibody Ki-67 (Ki-67 protein).
AB  - AIMS--To elucidate the fine specificities of the antibodies MIB 1 and MIB 3 and
      of additional monoclonal antibodies which also recognise the Ki-67 protein (MIB
      5, IND.64, JG-67-2a). METHODS--Different parts of the Ki-67 protein cDNA were
      expressed in Escherichia coli. Bacterial lysates were separated by sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and blotted on to
      nitrocellulose. Additionally different peptides were synthesised on a membrane
      support (SPOT-Blot). The immunoreactivity of the antibodies with the recombinant
      proteins and the immobilised synthetic peptides, respectively, was analysed. A
      competition enzyme linked immunosorbent assay (ELISA) using a soluble synthetic
      peptide was also performed. RESULTS--The epitopes of all antibodies tested were
      contained within the same region of seven amino acids. The antibodies MIB 1 and
      MIB 3 required the five amino acid sequence FKELF for binding, whereas Ki-67, JG
      67-2a, MIB 5 and IND.64 detected the sequence FKEL. CONCLUSIONS--It is concluded
      that the amino acid sequence FKELF represents an immunodominant area of the Ki-67
      protein and that there is no correlation between the ability to detect the Ki-67
      protein in paraffin wax sections irradiated with microwaves and the epitopes
      recognised by the antibodies.

PMID- 7520457
TI  - Projections to the cochlear nuclei from principal cells in the medial nucleus of
      the trapezoid body in guinea pigs.
AB  - Spherical and globular cells in the cochlear nucleus provide input to the cell
      groups in the superior olivary complex devoted to the analysis of binaural cues.
      Descending projections from the superior olivary complex appear to inhibit the
      spherical and globular cells. It is not known which of the numerous cell types in
      the superior olive provide this descending input, but recent studies have shown
      that some of the cells are located in the medial nucleus of the trapezoid body
      (MTB). The present experiments were designed to determine whether the MTB
      projections arise from principal cells, which are known to play a role in sound
      localization, and to determine whether their projections terminate on spherical
      or globular cells. Principal cells in the MTB are characterized by their contacts
      with synaptic specializations called calyces, which arise from the axons of cells
      in the contralateral cochlear nucleus. In the first experiment, a fluorescent
      tracer was injected into one cochlear nucleus to label the calyces anterogradely.
      A different tracer was injected into the opposite cochlear nucleus to label cells
      retrogradely in the MTB. In every case, some of the labeled cells were enveloped
      by a labeled calyx, demonstrating that principal cells do project to the cochlear
      nucleus. In the second experiment, fluorescent tracers were injected into
      different parts of the cochlear nucleus. Analysis of the distribution of labeled
      cells suggested that MTB projections selectively target the globular cell region
      of the cochlear nucleus. In a third experiment, the axonal arborizations arising
      from this projection were labeled with biocytin or wheat germ agglutinin
      conjugated to horseradish peroxidase. Labeled boutons appeared to contact
      globular cells but not spherical cells. Multipolar cells in the ventral cochlear
      nucleus and cells in the dorsal cochlear nucleus were also contacted. The results
      suggest that MTB projections to the cochlear nucleus arise largely from principal
      cells and contact, at least in part, cells in the cochlear nucleus that give rise
      to ascending pathways involved in sound localization.

PMID- 7520459
TI  - Psychometric properties of the children's atypical development scale.
AB  - The Children's Atypical Development Scale (CADS) is a 53-item rating scale
      designed to measure unusual behaviors in children. Principal-factor analysis on a
      clinic-referred and pediatric sample of 474 children resulted in a four-factor
      solution: Communication Deficits, Lability, Social Relatedness Deficits, and
      Preoccupation. The CADS is internally consistent and has adequate temporal
      stability. CADS factor scores were differentially associated with parent and
      teacher rating scales, IQ, and Continuous Performance Test errors. The scale
      shows promise as a clinical and research tool for assessing atypical behaviors
      associated with pervasive developmental disorder and other neurobehavioral
      disorders.

PMID- 7520458
TI  - Immunohistochemical distribution of CD44 and desmoplakin I & II in Hailey
      Hailey's disease and Darier's disease.
AB  - The cell-surface glycoprotein CD44 is found on a wide variety of cells including
      epidermal cells. It is involved in cell to cell adhesion. Desmoplakin I & II are
      important components of the attachment plaque of desmosomes. In this study, we
      compared the distribution patterns of anti-CD44 and anti-desmoplakin I & II in
      Hailey-Hailey's disease and Darier's disease. In the normal skin, anti-CD44
      stained the entire periphery of epidermal keratinocytes while anti-desmoplakin I
      & II produced dotted staining patterns along the periphery of epidermal
      keratinocytes. In Hailey-Hailey's disease and Darier's disease, the staining
      pattern of anti-CD44 on acantholized keratinocytes did not change, but anti
      desmoplakin I & II lost their peripheral, dotted patterns and stained diffusely
      in the cytoplasm in most acantholytic cells. These results suggest that, in
      Hailey-Hailey's disease and Darier's disease, CD44 may be intact even in
      acantholytic cells but abnormalities of desmoplakin exist in such cells.

PMID- 7520461
TI  - The use of a prostatic stent in high risk patients over 80 years old with benign
      prostatic hyperplasia and chronic retention.

PMID- 7520460
TI  - Major allergen Phl p Va (timothy grass) bears at least two different IgE-reactive
      epitopes.
AB  - It is established that most grass pollen allergens consist of several isoforms of
      which the function is mainly still unknown. A number of these allergens belonging
      to group V have been cloned, sequenced, and expressed. Antigenic sites and IgE
      reactive epitopes of the major allergen Phl p Va, are unknown. We have identified
      the complete cDNA sequence of a Phl p Va isoallergen by immunoscreening of a
      timothy grass pollen cDNA library and mixed oligonucleotide primed amplification
      of N-terminal cDNA. Additionally, we found an incomplete isoallergenic cDNA clone
      of the same protein. Immunoreactivity of the fusion proteins with patients' sera
      and monoclonal antibodies showed that the clones represent group Va allergens.
      Comparison of deduced amino acid sequences with published sequences of Lol p V
      and Poa p IX revealed a homology of 81.1% and 86.9%, respectively. With affinity
      purified IgE antibodies recognizing the recombinant fusion protein, we can
      demonstrate the existence of a common group V IgE-reactive epitope. By
      construction of both an N-terminal and a C-terminal peptide of the complete Phl p
      Va and cross-inhibition, we identified at least two different IgE epitopes.
      Eleven patients showed variable IgE immunoreactivities to both IgE-reactive
      epitopes.

PMID- 7520462
TI  - A chromatographic procedure for fully automated isolation of DNA from human whole
      blood.
AB  - Isolation of DNA from peripheral blood constitutes a fundamental step in the
      molecular diagnosis of genetic disorders, analysis of mutations of oncogenes and
      detection of nucleic-acid sequences of pathogenic organisms in clinical samples.
      We investigated whether dextran sedimentation of blood followed by the
      chromatographic isolation of DNA could be applied to the Biomek-1000 automated
      laboratory workstation in order to develop a fully automated method of DNA
      isolation from whole blood. Under our experimental conditions, the Biomek-1000
      could perform fully automated DNA isolation from seven human whole blood samples
      in less than 1.5 h. Our data indicate that the DNA isolated from human blood in
      this way is suitable for polymerase chain reaction.

PMID- 7520464
TI  - The spinal segmental and preganglionic projections from the brainstem in relation
      to the chicken cloaca.
AB  - Descending projections from the brainstem to the sympathetic and parasympathetic
      regions of the chicken spinal cord were investigated by means of the WGA-HRP
      method. The segmental and preganglionic injections of WGA-HRP were made into
      spinal segments 20-23 and 30-33 which were sympathetically and
      parasympathetically related to the cloaca, respectively. After injections of a
      large amount of WGA-HRP into each level of segments 20-23 and 30-33, the labeled
      SP-neurons (segmental projection neurons) were distributed mainly in the ventral
      half of the medulla in both cases. The distribution of these labeled neurons
      extended mainly to the central (20-23 segmental injections) and the lateral (30
      33 segmental injections) tegmental regions of the pons. In the mesencephalon,
      some SP-neurons were found in the dorsomedial reticular formation and the dorsal
      midline area, in addition to the Ru in both cases. By iontophoretic
      microinjections of WGA-HRP into the preganglionic regions of these segments, the
      labeled preganglionic projection neurons (PP-neurons) were found in the
      ventromedial part of the medulla. Both distributions of the labeled PP-neurons
      projecting to the sympathetic and parasympathetic regions were similar in the
      medulla. In the pons, although the sympathetic PP-neurons were found in the
      ventromedial pontine tegmentum, most of the parasympathetic PP-neurons were found
      in the dorsolateral tegmentum, e.g., the LoC-SC region. In the mesencephalon, a
      few sympathetic PP-neurons were found in the midline area ventromedial to the EW,
      but no parasympathetic PP-neurons were observed in the mesencephalon.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7520463
TI  - Monoclonal antibody COL-1 reacts with restricted epitopes on carcinoembryonic
      antigen: an immunohistochemical study.
AB  - We used a monoclonal antibody, MAb COL-1, which recognized a restricted epitope
      on the carcinoembryonic antigen (CEA) molecule, to stain a wide variety of human
      normal and cancerous tissues. None of the 35 different types of normal tissue
      stained with COL-1. Of 59 types of benign and malignant tissues, COL-1 reacted
      with neoplasms of epithelial origin, especially the gastrointestinal tract,
      breast, lung, and bladder. In benign adenomatous colon polyps, villous adenomas
      were more frequently stained than tubular adenomas. Normal colon tissue from
      individuals without colon disease was unreactive, but very weak reactivity was
      noted in normal-appearing mucosa several centimeters remote from colon cancers.
      In contrast, another anti-CEA antibody with a less restricted epitope reacted
      frequently with both normal and remote colon mucosa. These results indicate that
      MAb COL-1 recognizes a restricted CEA epitope expressed only on pre-malignant or
      malignant cells and therefore may be a useful reagent for immunopathology.

PMID- 7520466
TI  - The role of p21ras in CD28 signal transduction: triggering of CD28 with
      antibodies, but not the ligand B7-1, activates p21ras.
AB  - CD28 is a 44-kD homodimer expressed on the surface of the majority of human T
      cells that provides an important costimulus for T cell activation. The
      biochemical basis of the CD28 accessory signals is poorly understood. Triggering
      of the T cell antigen receptor (TCR) activates the p21ras proteins. Here we show
      that ligation of CD28 by a monoclonal antibody (mAb) also stimulates p21ras and
      induces Ras-dependent events such as stimulation of the microtubule-associated
      protein (MAP) kinase ERK2 and hyperphosphorylation of Raf-1. One physiological
      ligand for CD28 is the molecule B7-1. In contrast to the effect of CD28 mAb, the
      present studies show that interactions between CD28 and B7-1 do not stimulate
      p21ras signaling pathways. Two substrates for TCR-regulated protein tyrosine
      kinases (PTKs) have been implicated in p21ras activation in T cells: p95vav and a
      36-kD protein that associates with a complex of Grb2 and the Ras exchange protein
      Sos. Triggering CD28 with both antibodies and B7-1 activates cellular PTKs, and
      we have exploited the differences between antibodies and B7-1 for p21ras
      activation in an attempt to identify critical PTK-controlled events for Ras
      activation in T cells. The data show that antibodies against TCR or CD28 induce
      tyrosine phosphorylation of both Vav and p36. B7-1 also induces Vav tyrosine
      phosphorylation but has no apparent effect on tyrosine phosphorylation of the
      Grb2-associated p36 protein. The intensity of the Vav tyrosine phosphorylation is
      greater in B7-1 than in TCR-stimulated cells. Moreover the kinetics of Vav
      tyrosine phosphorylation is prolonged in the B7-1-stimulated cells. These studies
      show that for CD28 signaling, the activation of p21ras correlates more closely
      with p36 tyrosine phosphorylation than with Vav tyrosine phosphorylation.
      However, the experiments demonstrate that Vav is a major substrate for B7
      activated PTKs and hence could be important in CD28 signal transduction pathway.

PMID- 7520465
TI  - Immunity to malaria elicited by hybrid hepatitis B virus core particles carrying
      circumsporozoite protein epitopes.
AB  - The hepatitis B virus (HBV) nucleocapsid antigen (HBcAg) was investigated as a
      carrier moiety for the immunodominant circumsporozoite (CS) protein repeat
      epitopes of Plasmodium falciparum and the rodent malaria agent P. berghei. For
      this purpose hybrid genes coding for [NANP]4 (C75CS2) or [DP4NPN]2 (C75CS1) as
      internal inserts in HBcAg (between amino acids 75 and 81) were constructed and
      expressed in recombinant Salmonella typhimurium. The resulting hybrid HBcAg-CS
      polypeptides purified from S. typhimurium were particulate and displayed CS and
      HBc antigenicity, however, the HBc antigenicity was reduced compared to native
      recombinant HBcAg. Immunization of several mouse strains with HBcAg-CS1 and HBcAg
      CS2 particles resulted in high titer, P.berghei- or P.falciparum-specific anti-CS
      antibodies representing all murine immunoglobulin G isotypes. The possible
      influence of carrier-specific immunosuppression was examined, and preexisting
      immunity to HBcAg did not significantly affect the immunogenicity of the CS
      epitopes within HBcAg-CS1 particles. Similarly, the choice of adjuvant did not
      significantly alter the immunogenicity of HBcAg-CS hybrid particles. Immunization
      in complete or incomplete Freund's adjuvant or alum resulted in equivalent anti
      HBc and anti-CS humoral responses. Examination of T cell recognition of HBcAg-CS
      particles revealed that HBcAg-specific T cells were universally primed and CS
      specific T cells were primed if the insert contained a CS-specific T cell
      recognition site. This indicates that the internal site in HBcAg is permissive
      for the inclusion of heterologous pathogen-specific T as well as B cell epitopes.
      Most importantly, 90 and 100% of BALB/c mice immunized with HBcAg-CS1 particles
      were protected against a P. berghei challenge infection in two independent
      experiments. Therefore, hybrid HBcAg-CS particles may represent a useful approach
      for future malaria vaccine development.

PMID- 7520467
TI  - An invariant T cell receptor alpha chain is used by a unique subset of major
      histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and
      humans.
AB  - The mouse thymus contains a mature T cell subset that is distinguishable from the
      mainstream thymocytes by several characteristics. It is restricted in its usage
      of T cell receptor (TCR) V beta genes to V beta 8, V beta 7, and V beta 2. Its
      surface phenotype is that of activated/memory cells. It carries the natural
      killer NK1.1 surface marker. Furthermore, though it consists entirely of CD4+ and
      CD4-8- cells, its selection in the thymus depends solely upon major
      histocompatibility complex (MHC) class I expression by cells of hematopoietic
      origin. Forced persistence of CD8, in fact, imparts negative selection. Here, we
      have studied the TCR repertoire of this subset and found that, whereas the beta
      chain V-D-J junctions are quite variable, a single invariant alpha chain V alpha
      14-J281 is used by a majority of the TCRs. This surprisingly restricted usage of
      the V alpha 14-J281 alpha chain is dependent on MHC class I expression, but
      independent of the MHC haplotype. In humans, a similar unusual population
      including CD4-8- cells can also be found that uses a strikingly homologous,
      invariant alpha chain V alpha 24-JQ. Thus, this unique V alpha-J alpha
      combination has been conserved in both species, conferring specificity to some
      shared nonpolymorphic MHC class I/peptide self-ligand(s). This implies that the T
      cell subset that it defines has a specialized and important role, perhaps related
      to its unique ability to secrete a large set of lymphokines including interleukin
      4, upon primary stimulation in vitro and in vivo.

PMID- 7520468
TI  - Impaired cytotoxic T lymphocyte recognition due to genetic variations in the main
      immunogenic region of the human immunodeficiency virus 1 NEF protein.
AB  - Human immunodeficiency virus (HIV) induces strong responses from human
      histocompatibility leukocyte antigen (HLA) class I-restricted cytotoxic T
      lymphocytes (CTL). In a previous report we identified an immunodominant region
      (amino acids 73-144) in the NEF protein that was recognized by CD8+ class I
      restricted CTL of most asymptomatic individuals. Analysis of the 73-144 region by
      peptide sensitization, experiments using overlapping peptides corresponding to
      the LAI isolate identified the peptide sequences located between residues 73 and
      82 or 84 and 92 and the peptide sequence between residues 134 and 144 as cognate
      peptides for HLA-A11- and HLA-B18-restricted epitopes, respectively. This report
      describes the variable demonstrable reactivities of CTL obtained from HLA-A11 or
      HLA-B18 seropositive, asymptomatic patients who all had a response to the virus
      NEF protein, but who did not always recognize appropriate cognate peptides. The
      high mutation rate of HIV probably facilitates the selection of mutants that can
      avoid the cellular immune response. We therefore analyzed the variability of
      these epitopes restricted by HLA-A11 and HLA-B18. We sequenced several viral
      isolates from HLA-A11 and HLA-B18 donors who recognized certain HLA-peptide
      complexes and from those who did not. A CTL sensitization assay was used to show
      that some mutations led to a great reduction in CTL activity in vitro. This might
      be due to failure of the mutated epitope to bind major histocompatibility complex
      class I molecule. A simple assay was used to detect peptides that promoted the
      assembly of class I molecules. Some of these mutations at major anchor positions
      prevented HLA-A11/peptide binding, and consequently impaired recognition of the
      HLA-peptide complex by the T cell receptor.

PMID- 7520471
TI  - Virus escape from CTL recognition.

PMID- 7520470
TI  - Interferon gamma selectively inhibits very primitive CD342+CD38- and not more
      mature CD34+CD38+ human hematopoietic progenitor cells.
AB  - To assess the effects of interferon gamma (IFN-gamma) on very primitive
      hematopoietic progenitor cells, CD34(2+)CD38- human bone marrow cells were
      isolated and cultured in a two-stage culture system, consisting of a primary
      liquid culture phase followed by a secondary semisolid colony assay. CD34(2+)CD38
      cells needed at least the presence of interleukin 3 (IL-3) and kit ligand (KL)
      together with either IL-1, IL-6, or granulocyte-colony-stimulating factor (G-CSF)
      in the primary liquid phase in order to proliferate and differentiate into
      secondary colony-forming cells (CFC). Addition of IFN-gamma to the primary liquid
      cultures inhibited cell proliferation and generation of secondary CFC in a dose
      dependent way. This was a direct effect since it was also seen in primary single
      cell cultures of CD34(2+)CD38- cells. The proliferation of more mature CD34+CD38+
      cells, however, was not inhibited by IFN-gamma, demonstrating for the first time
      that IFN-gamma is a specific and direct hematopoietic stem cell inhibitor. IFN
      gamma, moreover, preserves the viability of CD34(2+)CD38- cells in the absence of
      other cytokines. IFN-gamma could, therefore, play a role in the protection of the
      stem cell compartment from exhaustion in situations of hematopoietic stress and
      may be useful as stem cell protecting agent against chemotherapy for cancer.

PMID- 7520469
TI  - The protective role of endogenously synthesized nitric oxide in staphylococcal
      enterotoxin B-induced shock in mice.
AB  - Nitric oxide (NO) synthesis during experimental endotoxemia has been shown to
      have both deleterious and beneficial effects. In the present study, we analyzed
      the in vivo production and the regulatory role of NO in the shock syndrome
      induced by staphylococcal enterotoxin B (SEB) in mice. First, we found that
      intraperitoneal administration of 100 micrograms SEB in BALB/c mice induced a
      massive synthesis of NO as indicated by high serum levels of nitrite (NO2-) and
      nitrate (NO3-) peaking 16 h after SEB injection. The inhibition of NO2- and NO3-
      release in mice injected with anti-tumor necrosis factor (TNF) and/or anti
      interferon gamma (IFN-gamma) monoclonal antibody (mAb) before SEB challenge
      revealed that both cytokines were involved in SEB-induced NO overproduction. In
      vitro experiments indicated that NO synthase (NOS) inhibition by N-nitro-L
      arginine methyl ester (L-NAME) enhanced IFN-gamma and TNF production by
      splenocytes in response to SEB. A similar effect was observed in vivo as
      treatment of mice with L-NAME resulted in increased IFN-gamma and TNF serum
      levels 24 h after SEB challenge, together with persistent expression of
      corresponding cytokine mRNA in spleen. The prolonged production of inflammatory
      cytokines in mice receiving L-NAME and SEB was associated with a 95% mortality
      rate within 96 h, whereas all mice survived injections of SEB or L-NAME alone.
      Both TNF and INF-gamma were responsible for the lethality induced by SEB in L
      NAME-treated mice as shown by the protection provided by simultaneous
      administration of anti-IFN-gamma and anti-TNF mAbs. We conclude the SEB induces
      NO synthesis in vivo and that endogenous NO has protective effects in this model
      of T cell-dependent shock by downregulating IFN-gamma and TNF production.

PMID- 7520472
TI  - Tissue expression of inducible nitric oxide synthase is closely associated with
      resistance to Leishmania major.
AB  - Previous studies with inhibitors of inducible nitric oxide synthase (iNOS)
      suggested that high-output production of nitric oxide (NO) is an important
      antimicrobial effector pathway in vitro and in vivo. Here, we investigated the
      tissue expression of iNOS in mice after infection with Leishmania major.
      Immunohistochemical staining with an iNOS-specific antiserum revealed that in the
      cutaneous lesion and draining lymph nodes (LN) of clinically resistant mice
      (C57BL/6), iNOS protein is found earlier during infection and in significantly
      higher amounts than in the nonhealing BALB/c strain. Similar differences were
      seen on the mRNA level as quantitated by competitive polymerase chain reaction.
      Anti-CD4 treatment of BALB/c mice not only induced resistance to disease, but
      also restored the expression of iNOS in the tissue. In situ, few or no parasites
      were found in those regions of the skin lesion and the draining LN which were
      highly positive for iNOS. By double labeling experiments, macrophages were
      identified as iNOS expressing cells in vivo. In the lesions of BALB/c mice, cells
      staining positively for transforming growth factor beta (TGF-beta), a potent
      inhibitor of iNOS in vitro, were strikingly more prominent than in C57BL/6,
      whereas no such difference was found for interleukin 4 or interferon gamma (IFN
      gamma). In vitro, production of NO was approximately threefold higher in C57BL/6
      than in BALB/c macrophages after stimulation with IFN-gamma. We conclude that the
      pronounced expression of iNOS in resistant mice is an important mechanism for the
      elimination of Leishmania in vivo. The relative lack of iNOS in susceptible mice
      might be a consequence of macrophage deactivation by TGF-beta and reduced
      responsiveness to IFN-gamma.

PMID- 7520473
TI  - T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and
      induce smooth muscle cell DNA synthesis.
AB  - Asthma is a disease of airway inflammation and hyperreactivity that is associated
      with a lymphocytic infiltrate in the bronchial submucosa. The interactions
      between infiltrating T lymphocytes with cellular and extracellular matrix
      components of the airway and the consequences of these interactions have not been
      defined. We demonstrate the constitutive expression of CD44 on human airway
      smooth muscle (ASM) cells in culture as well as in human bronchial tissue
      transplanted into severe combined immunodeficient mice. In contrast, basal levels
      of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule
      1 (VCAM-1) expression are minimal but are induced on ASM by inflammatory
      mediators such as tumor necrosis factor alpha (TNF-alpha). Activated, but not
      resting T cells, adhere to cultured ASM; stimulation of the ASM with TNF-alpha
      enhanced this adhesion. Adhesion was partially blocked by monoclonal antibodies
      (mAb) specific for lymphocyte function-associated antigen 1 (LFA-1) and very late
      antigen 4 (VLA-4) on T cells and ICAM-1 and VCAM-1 on ASM cells. The observed
      integrin-independent adhesion was mediated by CD44/hyaluronate interactions as it
      was inhibited by anti-CD44 mAb 5F12 and by hyaluronidase. Furthermore, the
      adhesion of activated T lymphocytes induced DNA synthesis in growth-arrested ASM
      cells. Thus, the interaction between T cells and ASM may provide insight into the
      mechanisms that induce bronchial inflammation and possibly ASM cell hyperplasia
      seen in asthma.

PMID- 7520479
TI  - Role of epidermal-dermal tissue interactions in regulating tenascin expression
      during development of the chick scutate scale.
AB  - During normal chicken development tenascin begins to accumulate in the dermis of
      anterior metatarsal skin at the time of scutate scale ridge formation, and is
      localized in a distinct pattern along the outer scale surface. Anterior
      metatarsal skin from scaleless (sc/sc) embryos, which do not form scutate scales,
      begins to accumulate tenascin 4 days later than normal skin. This study shows
      that normal and scaleless anterior metatarsal dermis accumulate the same tenascin
      isoforms and undergo the same isoform changes in the post-hatch period, but there
      is less tenascin accumulated in scaleless dermis and there is no pattern to its
      distribution. In both normal and scaleless anterior metatarsal skin, tenascin
      mRNA is localized in the dermis and is distributed in the same way as the
      protein. Thus, scaleless skin is defective in the ability to accumulate
      appropriate amounts of tenascin and to maintain the tenascin in the patterned
      manner of normal. Recombinant skin cultures show that epidermal-dermal
      interactions are required for tenascin accumulation. The dermis specifies the way
      that tenascin is organized, but interaction with epidermis is required to
      maintain this organization. The epidermal role appears to be permissive because
      in heterotypic recombinants, neither scaleless anterior metatarsal epidermis nor
      normal footpad epidermis changes the way that tenascin appears in the normal
      anterior metatarsal dermis; and in reciprocal recombinants, normal anterior
      metatarsal epidermis does not change the way tenascin is accumulated in either
      scaleless anterior metatarsal dermis or normal footpad dermis.

PMID- 7520474
TI  - Experimental autoimmune panencephalitis and uveoretinitis transferred to the
      Lewis rat by T lymphocytes specific for the S100 beta molecule, a calcium binding
      protein of astroglia.
AB  - The pathogenic potential of autoimmune T cell responses to nonmyelin autoantigens
      was investigated in the Lewis rat using the astrocyte-derived calcium binding
      protein S100 beta, as a model nonmyelin autoantigen. The Lewis rat mounts a
      vigorous RT1B1 (major histocompatibility complex class II) restricted autoimmune
      response to an immunodominant S100 beta epitope (amino acid residues 76-91). The
      adoptive transfer of S100 beta-specific T cell lines induced a severe
      inflammatory response in the nervous system, but only minimal neurological
      dysfunction in naive syngeneic recipients. The inability of S100 beta-specific T
      cell transfer to induce severe disease was associated with a decreased
      recruitment of ED1+ macrophages into the central nervous system (CNS) in
      comparison with that seen in severe experimental autoimmune encephalomyelitis
      (EAE) induced by the adoptive transfer of myelin basic protein (MBP)-specific T
      line cells. Moreover, unlike encephalitogenic MBP-specific T cell lines, S100
      beta-specific T cell lines exhibited no cytotoxic activity in vitro.
      Histopathological analysis also revealed striking differences in the distribution
      of inflammatory lesions in MBP- and S100 beta-specific T cell-mediated disease.
      In contrast to the MBP paradigm, S100 beta-specific T cell transfer induces
      intense inflammation not only in the spinal cord, but throughout the entire CNS
      and also in the uvea and retina of the eye. In view of the distribution of
      lesions throughout the grey and white matter of the CNS we propose to term this
      new model experimental autoimmune panencephalomyelitis (EAP) to differentiate it
      from EAE. These experiments demonstrate for the first time that nonmyelin CNS
      autoantigens can initiate a pathogenic autoimmune T cell response, although the
      nature of the target autoantigen profoundly influences the clinical and
      histopathological characteristics of the resulting autoimmune disease. This is
      not simply a consequence of the distribution of the autoantigen, as both MBP and
      S100 beta are coexpressed in many areas of the CNS, but reflects differences in
      the capacity of different regions of the CNS to process and present specific
      autoantigens. This new model of T cell-mediated autoimmune CNS disease exhibits a
      number of similarities to multiple sclerosis (MS), such as its mild clinical
      course and the involvement of areas of the brain and eye, which are absent in
      myelin-mediated models of EAE. Nonmyelin autoantigens may therefore play an
      unexpectedly important role in the immunopathogenesis of inflammatory diseases of
      the CNS.

PMID- 7520476
TI  - Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in
      patients chronically infected by variant viruses carrying substitutions within
      the epitope.
AB  - Mutations that abrogate recognition of a viral epitope by class I-restricted
      cytotoxic T lymphocyte (CTL) can lead to viral escape if the CTL response against
      that epitope is crucial for viral clearance. The likelihood of this type of event
      is low when the CTL response is simultaneously directed against multiple viral
      epitopes, as has been recently reported for patients with acute self-limited
      hepatitis B virus (HBV) infection. The CTL response to HBV is usually quite weak,
      however, during chronic HBV infection, and it is generally acknowledged that this
      is a major determinant of viral persistence in this disease. If such individuals
      were to produce a mono- or oligospecific CTL response, however, negative
      selection of the corresponding mutant viruses might occur. We have recently
      studied two HLA-A2-positive patients with chronic hepatitis B who, atypically,
      developed a strong HLA-A2-restricted CTL response against an epitope (FLPSDFFPSV)
      that contains an HLA-A2-binding motif located between residues 18-27 of the viral
      nucleocapsid protein, hepatitis B core antigen (HBcAg). These patients failed,
      however, to respond to any of other HLA-A2-restricted HBV-derived peptides that
      are generally immunogenic in acutely infected patients who successfully clear the
      virus. Interestingly, DNA sequence analysis of HBV isolates from these two
      patients demonstrated alternative residues at position 27 (V --> A and V --> I)
      and position 21 (S --> N, S --> A, and S --> V) that reduced the HLA and T cell
      receptor-binding capacities of the variant sequences, respectively. Synthetic
      peptides containing these alternative sequences were poorly immunogenic compared
      to the prototype HBc18-27 sequence, and they could not be recognized by CTL
      clones specific for the prototype peptide. While we do not know if the two
      patients were originally infected by these variant viruses or if the variants
      emerged subsequent to infection because of immune selection, the results are most
      consistent with the latter hypothesis. If this is correct, the data suggest that
      negative selection of mutant viral genomes might contribute to viral persistence
      in a subset of patients with chronic HBV infection who express a narrow
      repertoire of anti-HBV CTL responses.

PMID- 7520478
TI  - Role of interferon regulatory factor 1 in induction of nitric oxide synthase.
AB  - Interferon gamma (IFN-gamma) interacts synergistically with bacterial
      lipopolysaccharide (LPS) to induce transcription of iNOS, the isoform of nitric
      oxide synthase whose activity is independent of elevated Ca2+ and exogenous
      calmodulin. To define a cis-acting element mediating IFN-gamma-dependent synergy,
      we made deletions in iNOS promoter constructs fused to reporter genes,
      transfected RAW 264.7 macrophages, and treated the cells with IFN-gamma and/or
      LPS. This analysis implicated the region from positions -951 to -911, a cluster
      of four enhancer elements known to bind IFN-gamma-responsive transcription
      factors, including an interferon regulatory factor binding site (IRF-E) at
      nucleotides -913 to -923. Site-specific substitution of two conserved nucleotides
      within IRF-E in the context of the full-length iNOS promoter ablated IFN-gamma's
      contribution to synergistic enhancement of transcription. Electromobility shift
      assays performed with a probe containing IRF-E revealed the existence of a
      complex in nuclei of RAW 264.7 macrophages that was present only after treatment
      with IFN-gamma, which reacted specifically with anti-IRF-1 immunoglobulin G and
      which included a species migrating at 40-45 kD, consistent with the apparent
      molecular weight of murine IRF-1. Thus, the synergistic contribution of IFN-gamma
      to transcription of iNOS in RAW 264.7 macrophages requires that IRF-1 bind to IRF
      E in the iNOS promoter. In conjunction with the work of Kamijo et al. (Kamijo,
      R., H. Harada, T. Matsuyama, M. Bosland, J. Gerecitano, D. Shapiro, J. Le, K. S.
      Im, T. Kimura, S. Green et al. 1994. Science [Wash. DC]. 263:1612), these
      findings identify iNOS as the first gene that requires IRF-1 for IFN-gamma
      dependent transcriptional regulation.

PMID- 7520475
TI  - Transforming growth factor beta 1 is an inducer of erythroid differentiation.
AB  - Normal human bone marrow cells, highly enriched for burst-forming units-erythroid
      (BFU-E), were cultured in serum-free medium, in the presence and absence of
      various factors, to investigate the mechanisms involved in regulating erythroid
      differentiation. In cultures containing interleukin 3 (IL-3), Steel factor (SF),
      and erythropoietin (Ep), benzidine-positive erythroblasts first became detectable
      on day 6. Their numbers then rapidly increased until, by day 16, > 99% of the
      cells, which were 20,000-fold amplified over input numbers, were benzidine
      positive. It is interesting to note that omission of either SF or Ep from this
      assay markedly enhanced the rate of differentiation and reduced total cell
      numbers, whereas omission of IL-3 had no effect on the rate of differentiation
      and only slightly reduced cell numbers. Of various agents tested, the most potent
      erythroid differentiation inducer (and inhibitor of cell proliferation) was found
      to be transforming growth factor beta 1 (TGF-beta 1). This cytokine stimulated
      both the rapid appearance of hemoglobin-positive cells and an early cessation of
      cell proliferation. Using fluorescently tagged antibodies to glycophorin A and
      fluorescence-activated cell sorter (FACS) analysis, this phenomenon was shown to
      be due to an early induction of erythroid differentiation rather than an aberrant
      production of hemoglobin. Methylcellulose assays indicated that the well
      documented reduction of BFU-E colony numbers observed with TGF-beta 1 may
      actually be due to a TGF-beta 1-induced "conversion" of BFU-E into colony-forming
      units-erythroid (CFU-E). Thus, in vivo, TGF-beta 1 might serve, in part, to
      decrease the number of mature erythrocytes by stimulating BFU-E to skip a number
      of cell divisions and differentiate early.

PMID- 7520477
TI  - Iron regulates nitric oxide synthase activity by controlling nuclear
      transcription.
AB  - Recently, it was reported that nitric oxide (NO) directly controls intracellular
      iron metabolism by activating iron regulatory protein (IRP), a cytoplasmic
      protein that regulates ferritin translation. To determine whether intracellular
      iron levels themselves affect NO synthase (NOS), we studied the effect of iron on
      cytokine-inducible NOS activity and mRNA expression in the murine macrophage cell
      line J774A.1. We show here that NOS activity is decreased by about 50% in
      homogenates obtained from cells treated with interferon gamma plus
      lipopolysaccharide (IFN-gamma/LPS) in the presence of 50 microM ferric iron
      [Fe(3+)] as compared with extracts from cells treated with IFN-gamma/LPS alone.
      Conversely, addition of the iron chelator desferrioxamine (100 microM) at the
      time of stimulation with IFN-gamma/LPS increases NOS activity up to 2.5-fold in
      J774 cells. These effects of changing the cellular iron state cannot be
      attributed to a general alteration of the IFN-gamma/LPS signal, since IFN
      gamma/LPS-mediated major histocompatibility complex class II antigen expression
      is unaffected. Furthermore, neither was the intracellular availability of the NOS
      cofactor tetrahydrobiopterin altered by treatment with Fe(3+) or desferrioxamine,
      nor do these compounds interfere with the activity of the hemoprotein NOS in
      vitro. We demonstrate that the mRNA levels for NOS are profoundly increased by
      treatment with desferrioxamine and reduced by Fe(3+). The half-life of NOS mRNA
      appeared not to be significantly altered by administration of ferric ion, and NOS
      mRNA stability was only slightly prolonged by desferrioxamine treatment. Nuclear
      run-off experiments demonstrate that nuclear transcription of cytokine-inducible
      NOS mRNA is strongly increased by desferrioxamine whereas it is decreased by
      Fe(3+). Thus, this transcriptional response appears to account quantitatively for
      the changes in enzyme activity. Our results suggest the existence of a regulatory
      loop between iron metabolism and the NO/NOS pathway.

PMID- 7520480
TI  - Clinical and histological findings in proteolipid protein-induced experimental
      autoimmune encephalomyelitis (EAE) in the Lewis rat. Distribution of
      demyelination differs from that in EAE induced by other antigens.
AB  - Proteolipid protein (PLP) is the major protein of central nervous system (CNS)
      myelin. In some species, intradermal inoculation with PLP and adjuvants causes
      experimental autoimmune encephalomyelitis (PLP-EAE) characterized by neurological
      signs of tail and limb weakness and by inflammation and demyelination in the CNS.
      A previous study found that inoculation of Lewis rats with 100 micrograms of PLP
      causes PLP-EAE with a low incidence of neurological signs and a highly variable
      clinical course. In the present study we assessed PLP-EAE produced by inoculation
      with 1000 micrograms of PLP per rat. Fifty-one of 59 (86%) Lewis rats developed
      neurological signs 8 to 20 days (mean = 12.0 +/- 2.0) after inoculation with 1000
      micrograms of PLP. In such rats, mononuclear cell infiltrates were present in the
      brain and spinal cord while primary demyelination occurred mainly in the subpial
      regions of the spinal cord, especially in the dorsal root entry and ventral root
      exit zones. The histological findings were compared with those in acute EAE
      induced in the Lewis rat by inoculation with whole CNS tissue or with myelin
      basic protein: in PLP-EAE, in contrast to these other models, the disease was
      essentially restricted to the CNS. This form of EAE should be useful in future
      studies of the consequences of autoimmunity to PLP.

PMID- 7520483
TI  - Cholecystokinin-stimulated intracellular signal transduction pathways.
AB  - Cholecystokinin stimulates a variety of physiological effects throughout the
      gastrointestinal tract, including exocrine pancreatic secretion, contraction of
      gallbladder and smooth muscle throughout the gastrointestinal tract, relaxation
      of the sphincter of Oddi and inhibition of gastric emptying. To initiate these
      responses cholecystokinin must first interact with receptors on the plasma
      membrane of either pancreatic acinar or smooth muscle cells. Following receptor
      occupation the receptor is coupled to generation of intracellular messengers,
      such as ions, cyclic nucleotides or derivatives of phospholipid hydrolysis. These
      intracellular messengers activate effectors, the systems that cause a biological
      response. This paper uses the exocrine pancreas as a model for cholecystokinin
      stimulated signal transduction and examines cholecystokinin stimulated
      mobilization of calcium and the activation of protein kinase C. Calcium and
      protein kinase C act differently to mediate either the initial or sustained
      phases of amylase secretion from the pancreas. The activation of protein kinase C
      and the rise of intracellular free calcium is necessary for the initial phase of
      secretion, but unimportant for the sustained phase of secretion. Calcium from
      extracellular sources is necessary for the sustained phase of secretion. The
      cholecystokinin-stimulated intracellular signaling outlined for the exocrine
      pancreas also occurs in other tissues for transmitting the signal from the
      cholecystokinin receptor to the inside of the cell.

PMID- 7520481
TI  - Transmembrane ion movements elicited by sodium pump inhibition in Helix aspersa
      neurons.
AB  - 1. Transmembrane ion movements upon sodium-pump inhibition were studied in
      identified neurons of the subesophageal ganglia of Helix aspersa. A two
      microelectrode, voltage-clamp technique was used to measure transmembrane
      currents. Changes in intracellular Na+, K+, and Ca2+ concentrations were
      measured, in unclamped neurons, with Na(+)-sensitive microelectrodes, K(+)
      sensitive microelectrodes, and with the fluorescent probe fura-2, respectively.
      2. Inhibition of the sodium pump with ouabain (1 mM) elicited an increase in
      intracellular Na+ concentration, [Na+]i, at an initial rate of 0.42 +/- 0.05
      mM/min (mean +/- SE; n = 27), and a membrane depolarization often followed by
      hyperpolarization. In cells clamped at -50 or -60 mV, ouabain produced an inward
      shift in membrane-holding current followed by an outward current usually having
      two components, transient and sustained, respectively. 3. Replacing external Na+
      with either N-methyl-D-glucammonium or tetraethylammonium (TEA+) abolished both
      the ouabain-induced inward membrane current and the rise in [Na+]i, suggesting
      that Na+ was the charge carrier of the inward current. 4. Cd2+ (400 microM)
      reduced the rate of rise of the inward current by 60% and the estimated net Na+
      flux by 47%. 5. The outward current was abolished by K(+)-channel blockers (10 mM
      TEA+ and 5 mM 4-aminopyridine or 10 nM apamin). Cd2+ (400 microM), a Ca(2+)-entry
      blocker, also abolished the outward current. 6. Inhibition of the sodium pump
      elicited a fall in [K+]i at an initial rate of 1.4 +/- 0.2 mM/min (n = 9 cells).
      7. Upon inhibition of the sodium pump in neurons loaded with fura-2, [Ca2+]i
      increased from an estimated resting level of 147 +/- 37 nM to a maximum of 764 +/
      248 nM (n = 12 cells). 8. The rise in [Ca2+]i in the sustained presence of
      ouabain was transient, lasting 19.5 +/- 2.8 min, and could be prevented by
      removal of external Ca2+ before ouabain application or curtailed by removal of
      external Ca2+ during sustained ouabain exposure. The latter effect was not a
      consequence of exhaustion of caffeine-sensitive intracellular Ca2+ stores. 9. It
      is concluded that 1) the rise in [Ca2+]i upon Na(+)-pump inhibition requires the
      presence of external Ca2+, 2) the outward current observed upon pump inhibition
      is a Ca(2+)-activated K+ current flowing through apamin-sensitive channels, 3)
      the resting Na+ permeability involves a Cd(2+)-sensitive component, 4) a large
      fraction (approximately 30-60%) of the previously described ouabain-induced cell
      shrinkage may result from Ca(2+)-activated K+ efflux contributing to net solute
      and water loss.

PMID- 7520482
TI  - Distribution and functional properties of 5-HT3 receptors in the rat hippocampal
      dentate gyrus: a patch-clamp study.
AB  - 1. In dentate gyrus of rat hippocampal slices two distinct types of neurons,
      principal excitatory neurons (granule cells) and local inhibitory neurons (basket
      cells), could be identified under Nomarski microscopy; I investigated the actions
      of serotonin using the whole-cell patch-clamp technique. The identification of
      the neurons was later confirmed by intracellular staining with Lucifer yellow. 2.
      In both basket cells and granule cells, whole-cell current recordings revealed
      spontaneous synaptic currents ranging from < 10 pA to > 200 pA in symmetrical Cl-
      conditions at a holding potential of -63 mV. These currents were blocked by 10
      microM bicuculline, indicating that they resulted from the spontaneous activation
      of GABAergic inputs (which had been morphologically described in both types of
      neurons). 3. By focal application of serotonin (2-50 microM) to basket cells
      under current clamp I evoked a train of action potentials superimposed on a
      baseline membrane depolarization. Under voltage-clamp conditions serotonin evoked
      an inward current at a holding potential of -63 mV (currents were detectable in
      approximately 90% of basket cells studied). The inward current was accompanied by
      a multitude of small inward currents of short duration (< 100 ms) that were found
      to be due to the stimulation by serotonin of nearby GABAergic presynaptic neurons
      innervating the recorded neuron. 4. In granule cells (total of 11 cells)
      serotonin did not produce any responses under conditions similar to those used
      for basket cells. The occurrence of bicuculline-sensitive spontaneous synaptic
      current events seemed to increase during the application of serotonin; this
      phenomenon reflected the excitatory action of serotonin exclusively on GABAergic
      interneurons. 5. The serotonin-induced inward currents in basket cells were
      mediated by the 5-HT3 receptor subtype because 1) they were blocked by either
      metoclopramide (10 microM) or [3-alpha-tropanyl]-1H-indolecarboxylic acid ester
      (2 nM), the latter being a specific blocker for the 5-HT3 receptor subtype, and
      2) almost similar currents were induced by the application of the selective 5-HT3
      receptor agonist 2-methyl 5-HT (2-50 microM) or 1-(m-chlorophenyl)-biguanide (0.1
      10 microM). 6. Current-voltage (I-V) relations of serotonin-induced currents in
      basket cells showed that the reversal potential was close to 0 mV in external
      standard saline and depended on the concentrations of monovalent cations. I-V
      relations of serotonin-induced currents revealed inward rectification at the
      membrane potential range of +30 to -60 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7520484
TI  - Cell culture as a tool for identifying nutritional disease therapies.
AB  - Cell culture methodologies can be used to help develop therapies for the
      treatment of polytrauma. An overview is presented of research with the L6
      myoblast cell line that led to the discovery of the truncated insulin-like growth
      factor (IGF) variant, des(1-3)IGF-I and that gave an explanation of the enhanced
      potency of this growth factor. Subsequent efforts to develop an even more potent
      variant also utilized cultured cells as indicator bioassays. Such experiments not
      only provided mechanistic information on IGF action but also directed attention
      towards IGF variants that were later shown to be more potent in vivo at reversing
      catabolic conditions.

PMID- 7520485
TI  - Differential levels of synovial fluid aggrecan aggregate components in
      experimental osteoarthritis and joint disuse.
AB  - The levels of proteoglycan aggregate components (link protein, keratan sulfate
      epitope, and total sulfated glycosaminoglycan) were determined in the synovial
      fluid lavages of dogs with experimental osteoarthritis or disuse atrophy. A model
      of experimental osteoarthritis was created by transection of the anterior
      cruciate ligament of the right knee; studies were carried out 6 and 12 weeks
      after surgery. Joint disuse was studied at 4 and 8 weeks after initiation of the
      disuse. Recovery after disuse also was studied in joints that had 3 weeks of
      remobilization after 4 or 8 weeks of disuse. Synovial fluid lavages from the
      right knee joints of untreated animals were used as controls. The concentrations
      of keratan sulfate epitope, sulfated glycosaminoglycan, and link protein in the
      synovial fluid lavages at 6 and 12 weeks after transection of the anterior
      cruciate were elevated compared with the control values. Similar analysis of the
      fluid after disuse showed that the levels of keratan sulfate epitope and sulfated
      glycosaminoglycan were increased compared with the control levels and the levels
      after transection. However, the concentration of link protein in the fluid after
      disuse was not significantly different from the control level. The levels of
      keratan sulfate epitope and sulfated glycosaminoglycan in the synovial fluid
      lavages after disuse with recovery were high, but the levels of link protein
      remained low. The results indicate that the catabolism of proteoglycan aggregates
      in articular cartilage during early osteoarthritis and disuse is different. The
      determination of keratan sulfate epitope in synovial fluid lavages appears to
      provide a relatively general indication of proteoglycan catabolism, whereas
      increased levels of link protein may be more indicative of cartilage
      degeneration.

PMID- 7520486
TI  - Culture surfaces coated with various implant materials affect chondrocyte growth
      and metabolism.
AB  - The effect on chondrocyte metabolism of culture surfaces sputter-coated with
      various materials used for orthopaedic implants was studied and correlated with
      the stage of cartilage cell maturation. Confluent, fourth-passage chondrocytes
      from the costochondral resting zone and growth zone of rats were cultured for 6
      or 9 days on 24-well plates sputter-coated with ultrathin films of titanium,
      titanium dioxide, aluminum oxide, zirconium oxide, and calcium phosphate
      (1.67:1). Corona-discharged tissue culture plastic served as the control. The
      effect of surface material was examined with regard to cell morphology; cell
      proliferation (cell number) and DNA synthesis ([3H]thymidine incorporation); RNA
      synthesis ([3H]uridine incorporation); collagenase-digestible protein,
      noncollagenase-digestible protein, and percentage of collagen production; and
      alkaline phosphatase-specific activity, both in the cell layer and in trypsinized
      chondrocytes. Cell morphology was dependent on surface material; only cells
      cultured on titanium had an appearance similar to that of cells cultured on
      plastic. While titanium or titanium dioxide surfaces had no effect on cell number
      or [3H]thymidine incorporation, aluminum oxide, calcium phosphate, and zirconium
      oxide surfaces inhibited both parameters. Cells cultured on aluminum oxide,
      calcium phosphate, zirconium oxide, and titanium dioxide exhibited decreased
      collagenase-digestible protein, noncollagenase-digestible protein, and percentage
      of collagen production, but [3H]uridine incorporation was decreased only in those
      chondrocytes cultured on aluminum oxide, calcium phosphate, or zirconium oxide.
      Chondrocytes cultured on titanium had greater alkaline phosphatase-specific
      activity than did cells cultured on plastic, but the incorporation of [3H]uridine
      and production of collagenase-digestible protein, noncollagenase-digestible
      protein, and percentage of collagen was comparable. The response of chondrocytes
      from the growth zone and resting zone to culture surface was comparable,
      differing primarily in magnitude. Cell maturation-dependent effects were evident
      when enzyme activity in trypsinized and scraped cells was compared. These results
      indicate that different surface materials affect chondrocyte metabolism and
      phenotypic expression in vitro and suggest that implant materials may modulate
      the phenotypic expression of cells in vivo.

PMID- 7520488
TI  - [Immunohistological investigation of squamous metaplasia and expression of
      cytokeratin subclasses in laryngeal epithelia].
AB  - The expression of cytokeratin (CK) subclasses was immunohistologically
      investigated in normal laryngeal epithelia by the ABC technique using
      monospecific monoclonal antibodies. There are two types of epithelium in the
      larynx; squamous epithelium of the glottis and ciliated epithelium mainly of the
      supraglottis. A difference in expression pattern was observed between these two
      epithelia only in 3 CKs, specifically CK-8, CK-13 and CK-19. In the glottis, CK-8
      was negative in all layers, CK-13 was positive in the suprabasal and superficial
      layers, and CK-19 was strongly positive in the basal layer, but apparently
      reduced in suprabasal layers and completely negative in the superficial layers.
      In the supraglottis, on the contrary, CK-8 was positive except in the basal
      layer, CK-13 was negative in all layers, and CK-19 was positive in all layers.
      When ciliated epithelia were reduced to squamous metaplasia, the epithelial cells
      were morphologically similar to the squamous cells, and the CK expression also
      showed the same pattern. In proximity to this squamous metaplasia, however, there
      were lesions whose cell type morphologically still resembled that of the ciliated
      epithelium, but whose pattern of CK expression had already been reduced to that
      of the squamous cell.

PMID- 7520487
TI  - Influence of exogenous growth factors on the expression of plasminogen activators
      and plasminogen activator inhibitors by cells isolated from normal and healing
      rabbit ligaments.
AB  - In this investigation, we demonstrate that cells from normal and healing rabbit
      ligaments are selective in their responsiveness to various growth factors. The
      cells analyzed included fibroblasts isolated from the synovium, the anterior
      cruciate ligament, and the medial collateral ligament (midsubstance and
      epiligament). Fibroblasts isolated from scar tissue of medial collateral ligament
      that had been allowed to heal for 3 weeks also were analyzed. The addition of
      insulin-like growth factor-2 or transforming growth factor-beta 1 was observed to
      alter, in a dose-dependent manner, the expression of plasminogen activator and
      plasminogen activator inhibitor by connective tissue cells. However, the response
      to these growth factors was cell specific. Fibroblasts isolated from the
      midsubstance, epiligament, and scar tissue of the medial collateral ligament were
      responsive to these growth factors; fibroblasts isolated from the anterior
      cruciate ligament and synovium did not have a detectable response. The cells from
      the normal and healing medial collateral ligament responded to both growth
      factors by increasing plasminogen activator inhibitor activity. This was observed
      at both the protein and RNA level. In contrast, the addition of insulin-like
      growth factor-1 or acidic or basic fibroblast growth factor to cells derived from
      normal or healing ligament did not result in any detectable alteration of
      plasminogen activator or plasminogen activator inhibitor activity. These results
      are similar to those observed with an explant system and indicate that cells
      isolated from ligament tissue maintain their responsiveness to these growth
      factors in the absence of matrix. As the major effect of insulin-like growth
      factor-2 and transforming growth factor-beta 1 on the cells tested was to
      increase plasminogen activator inhibitor activity, such an alteration should
      diminish the activity of plasminogen activator, an enzyme capable of directly and
      indirectly proteolyzing matrix molecules, and thus contribute to a more anabolic
      environment.

PMID- 7520489
TI  - [Vasoactivity of human nasal mucosa in response to sensory neurotransmitters (a
      study of nasal geometrical change with acoustic rhinometry)].
AB  - Intranasal blood flow is regulated not only by autonomic but also by sensory
      nervous systems. Sensory neurotransmitters are reported to control resistance
      vessels. Our investigation of intranasal vasoactivity before and after applying
      sensory neurotransmitters was conducted using acoustic rhinometry. Acoustic
      rhinometry is a modern method of evaluating the cross-sectional area and volume
      of the nasal cavity. Its characteristics are that it is a non-traumatic
      procedure, minimal time is required for measurements and reliability is high. In
      the present experiment, calcitonin gene-related peptide (CGRP) and substance P
      (SP) were used as the sensory neurotransmitters. Six males (26-39 years old),
      without nasal abnormalities, were examined for one hour with acoustic rhinometry
      before and after administration of these transmitters. Nose drops of these
      preparations were introduced into one nasal cavity of each candidates, while in
      the head tilt position. After application of nose drops, both sides were
      evaluated with acoustic rhinometry in regard to minimal cross sectional area
      (MCSA) and nasal volume. Both CGRP and SP decreased the MCSA and volume on the
      applied side within ten minutes, which was followed by a plateau level for 1
      hour. The opposite sides showed no significant change in either MCSA or volume.
      Changes in the MCSA ratio increased dose-dependently as the concentration of CGRP
      or SP increased. Changes in the volume ratio decreased when the concentration of
      SP was increased from 10(-8) to 10(-7) M, while it converted and then rose at 10(
      6) M. CGRP has a potent vasodilator effect on vascular smooth muscles. SP also
      induces relaxation of vascular tone via endothelial cells.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7520490
TI  - Localization of peroxidase activity in tegumental, muscle, and parenchymal cells
      of the lung fluke Paragonimus miyazakii (Digenea: Troglotrematidae).
AB  - The distribution and localization of peroxidase activity were examined in adults
      of Paragonimus miyazakii in sections stained with 3,3'-diaminobenzidine in the
      presence of hydrogen peroxide. Peroxidase activity was detected in tegumental
      cell mitochondria. With cell development, the reaction intensity became greater.
      Activity extended from the inner membrane (undifferentiated stage) to the
      intermembrane space (differentiating stage) and then to the matrix
      (differentiated stage). Mitochondria with the most intense reaction were densely
      distributed in the outer syncytial region. Strong activity was also present in
      mitochondria of muscle cells and in those of Type II parenchymal cells.
      Intermembrane spaces were the predominant site of this activity.
      Characteristically, both 10 mM azide and 1 mM cyanide were mildly effective in
      the inhibition of mitochondrial peroxidase activity in each cell type.

PMID- 7520491
TI  - Selective uptake of liposomes containing lactose mono-fatty acid derivatives by
      hepatic parenchymal cells.
AB  - In this study we investigated the hepatic uptake of liposomes containing a novel
      synthetic glycolipid, lactose mono-arachidic acid amide (LAA). Liposomes
      containing LAA were aggregated by Ricinus communis agglutinin from caster bean,
      while the control liposomes were not, and the results suggested that the
      galactose residues of LAA were exposed to the outer surface of the liposomes.
      Next, the blood clearance and hepatic uptake of liposomes containing LAA after
      intravenous administration were compared with those of the control liposomes in
      rat. Hepatic uptake of liposomes containing LAA was greater than that of the
      control liposomes, rising significantly with dose. As a result of separation of
      the parenchymal and non-parenchymal cells, it was shown that the increase in
      hepatic uptake was mostly accounted for by a greater uptake by parenchymal cells.
      The inhibitory activity of asialofetuin on the hepatic uptake of liposomes
      containing LAA suggested that a galactose-specific recognition is involved in
      this uptake. These results demonstrate that the lactose mono-fatty acid amides
      (LFAs) are promising novel compounds for the introduction of carbohydrate
      residues onto the liposomal surface and that liposomes containing LFAs are
      potential carriers for the selective delivery of drugs to specific cells.

PMID- 7520493
TI  - Late hyphema after small incision cataract surgery.
AB  - A 68-year-old patient presented with a spontaneous hyphema 11 months after
      successful small incision cataract surgery. There was evidence of
      neovascularization of the wound. The intraocular lens was sequestered in the
      capsular bag within an intact capsulorhexis. Wound neovascularization as a
      complication of cataract surgery has become extremely rare with the increase in
      the popularity of the corneal incision for extracapsular cataract surgery. But
      the complication could become more common with the return to scleral incisions
      for phacoemulsification. Precise wound construction is necessary to avoid this
      complication.

PMID- 7520492
TI  - Phenyl alanine, tryptophan immobilized chitosan beads as adsorbents for selective
      removal of immunoproteins.
AB  - The use of adsorbents for the treatment of patients suffering from various immune
      diseases is still in its infancy. Therefore, the development of selective
      absorbents for the removal or decrease of immunoproteins from plasma is of great
      importance. In this study, chitosan, a natural polysaccharide having structural
      characteristics similar to glycosamino glycans, which is non-toxic and
      biocompatible, has been used for protein adsorption studies. Amino acids like
      phenyl alanine and tryptophan in different ratios are bonded to these polymers to
      observe immunoadsorption. Several layers of phenyl alanine or tryptophan have
      been coated covalently on chitosan beads using N2-plasma, carbodiimide or
      glutaraldehyde treatments. Scanning electron micrographs have revealed the
      surface morphological changes after such modifications. The surface modified
      chitosan beads have exhibited high binding affinity for gamma-globulin compared
      to bare beads. It is also observed that the amount of fibrinogen adsorption is
      reduced on modified substrate. A selective removal of IgG and IgM has also been
      observed with these modified matrix when tested with human plasma, using immuno
      diffusion methods. The modified chitosan membranes have demonstrated a reduction
      in platelet attachment, showing that these substrates have become more blood
      compatible. Hence, it appears that modified chitosan surfaces may be an excellent
      sorbent system for haemoperfusion due to their high binding affinity for
      immunoproteins and blood compatibility. Further studies are needed to determine
      the behaviour under clinical conditions.

PMID- 7520494
TI  - The use of hetastarch as adjunct therapy in 26 dogs with hypoalbuminemia: a phase
      two clinical trial.
AB  - The purpose of this study was to evaluate the safety and efficacy of the
      synthetic colloid hetastarch in dogs with hypoalbuminemia. Individual doses of
      hetastarch ranged from 9 to 27 mL/kg, and multiple doses were used frequently.
      Total doses ranged from 9 to 59 mL/kg. Colloid oncotic pressure was measured in
      13 dogs before and after treatment. Mean colloid oncotic pressure +/- SD was 9.32
      +/- 2.35 mm Hg before treatment and 16.41 +/- 1.61 mm Hg in 8 healthy pet dogs
      used as controls. The difference in these values was significant (P < .001).
      There was a significant increase in mean colloid oncotic pressure after the first
      dose of hetastarch, but there was no relationship between the dose of hetastarch
      and the magnitude of increase in colloid oncotic pressure. Peripheral edema or
      body cavity transudates resolved or decreased in 83% of the dogs despite
      concurrent use of crystalloid fluid therapy. There was also no relationship
      between the dose of hetastarch and resolution of edema. Worsening of the results
      from coagulograms occurred in 5 of 18 dogs, and included increased prothrombin
      time (n = 1), increased partial thromboplastin time (n = 5), and decreased
      platelet count (n = 3). Bleeding that occurred in 3 dogs could not be directly
      attributed to the hetastarch. There was no relationship between the dose of
      hetastarch and worsening of the values in the coagulograms.

PMID- 7520495
TI  - Double staining in situ study of mRNAs encoding milk proteins in the mammary
      gland of the tammar wallaby (Macropus eugenii).
AB  - Oligonucleotides, differentially tagged with fluorochromes, were used to
      determine whether the distribution of mRNAs encoding the major milk proteins is
      heterogeneous within the mammary gland of the tammar wallaby (Macropus eugenii).
      This method also allowed direct visualization of two species of mRNA within the
      same cell. Sections of early and late lactating glands of tammar wallabies were
      hybridized with oligonucleotides labelled with fluorescein isothiocyanate or
      rhodamine isothiocyanate either alone or in combination. The results support the
      hypothesis that milk secretion is an all-or-none process with all epithelial
      cells in a given alveolus producing the same suite of milk proteins. In tammar
      wallabies, a gene encoding a protein specific to the latter phase of lactation
      appears to be expressed in those cells already secreting the other major milk
      proteins.

PMID- 7520496
TI  - Epithelial localization of insulin-like growth factor binding protein 1 in the
      uterus of the rat during pregnancy, deciduoma-bearing pseudopregnancy and hormone
      treatment.
AB  - A monospecific antibody was used to determine the immunocytochemical localization
      of insulin-like growth factor binding protein 1 (IGFBP-1) in the rat uterus.
      Immunoreactive IGFBP-1 was first detected from day 5 of pregnancy in the luminal
      and glandular epithelium. However, immunoreactivity was most intense from day 6
      in the glandular epithelium, where it was associated with apically located
      granules. Immunoreactive glands were located only in non-decidualized
      endometrium, which was limited at the implant site to a thin basal layer by
      growth of the antimesometrial decidua from day 7. However, glands and associated
      immunoreactive IGFBP-1 were prominent in the inter-implant sites until day 9,
      although they were detected throughout pregnancy. Similar reactivity was detected
      in the glands of the basal endometrium in deciduomata-bearing animals, but these
      decreased in number from day 7 of pseudopregnancy. No immunoreactivity was
      detected during the oestrous cycle but could be induced in ovariectomized animals
      by sequential oestradiol and oestradiol plus progesterone treatment. The
      observations were consistent with IGFBP-1 representing a secretory product of the
      glandular epithelium and could either play a role in development of the
      trophoblastic component of the conceptus during the pre-placental period of anti
      mesometrial implantation or in the endometrium acting as an inhibitor of local
      IGF-I action and in either case by transporting IGF-I from the stromal to the
      glandular luminal environment.

PMID- 7520498
TI  - Metastatic trophoblastic neoplasm: Report of a case with a delay in diagnosis
      resulting from an unusual presentation.
AB  - Choriocarcinoma is so rare and presents such different pictures that its
      diagnosis may be delayed or missed entirely, depriving the patient of early
      treatment and the chance of a cure. This paper describes such a case and
      emphasizes the importance of maintaining a high degree of suspicion for
      trophoblastic disease and its complications.

PMID- 7520497
TI  - Hyalinization and cellular changes in uterine leiomyomata after gonadotropin
      releasing hormone agonist therapy.
AB  - This study evaluated the microscopic changes in leiomyomata following the use of
      a gonadotropin releasing hormone (GnRH) agonist. Seventeen women with symptomatic
      leiomyomata were included. Nine were treated with a GnRH agonist for three to six
      months prior to surgery, and the remaining eight served as controls. Following
      myomectomy, paraffin sections were prepared from the tumors. These sections were
      examined microscopically by two gynecologic pathologists, who were blind to the
      patient groups. The results showed increased cellularity and hyalinization in
      leiomyomata following GnRH agonist treatment.

PMID- 7520499
TI  - Remarkable elevation of interleukin 6 and interleukin 8 levels in the bone marrow
      serum of patients with rheumatoid arthritis.
AB  - OBJECTIVE: Characteristic cellular changes have previously been reported in the
      bone marrow of patients with rheumatoid arthritis (RA). We investigated the
      levels of various cytokines in RA bone marrow. METHODS: We studied 25 patients
      with RA (22 women and 3 men) and 10 trauma patients (7 women and 3 men) as non-RA
      controls. Twelve kinds of cytokines [interleukin (IL)-1 alpha, IL-1 beta, IL-2,
      IL-3, IL-4, IL-6, IL-7, IL-8, granulocyte colony stimulating factor,
      granulocyte/macrophage colony stimulating factor, tumor necrosis factor (TNF)
      alpha, and TNF-beta] were assayed by ELISA in iliac bone marrow serum (BMS),
      tibial BMS, and peripheral blood serum. RESULTS: Markedly elevated levels of IL-6
      and IL-8 were detected in iliac BMS, and much lower levels were found in tibial
      bone marrow and peripheral blood serum. The levels of IL-6 and IL-8 in iliac BMS
      showed a close relationship to the extent of synovial proliferation. CONCLUSION:
      Iliac bone marrow may be an important site for the production or accumulation of
      IL-6 and IL-8 in RA, and these cytokines may influence synovial proliferation in
      patients with polyarthritis.

PMID- 7520500
TI  - Distribution of substance P and calcitonin gene related peptide immunoreactivity
      in the normal feline knee.
AB  - OBJECTIVE: There is substantial evidence that the intraarticular release of the
      neuropeptides substance P (SP) and/or calcitonin gene related peptide (CGRP) can
      contribute to the development and perpetuation of joint inflammation. However,
      there is a paucity of data examining whether SP and CGRP containing fibers are
      present in articular tissues other than synovium. Our objective was to
      comprehensively examine all innervated tissues in the normal feline knee for the
      presence of these neuropeptides. METHODS: The normal right knee joints from 5
      cats were harvested and dissected into 10 regions. These regions included the
      cruciate and collateral ligaments, menisci, fat pad and synovium, capsule and
      popliteus tendon. Each area was examined for the immunocytochemical presence of
      SP and CGRP. RESULTS: Nerve fibers immunoreactive (Ir) for SP or CGRP were found
      in all of the joint tissues examined. In general, Both SP-Ir and CGRP-Ir nerve
      fibers were most often associated with blood vessels. However, there were "free"
      SP and CGRP fibers present in all 10 articular structures which were not
      associated with any vascular profiles. CONCLUSION: Our data demonstrate that
      articular SP and CGRP-Ir fibers are not limited to the synovium. Both
      neuropeptides are widely distributed to all joint tissues except articular
      cartilage, which is devoid of neural tissue. These findings, in conjunction with
      an increasing appreciation of the functional interrelationship between SP and
      CGRP, argue cogently for consideration of the effects generated by nonsynovial
      sources of SP and CGRP when assessing the role of these neuropeptides in both
      normal joint function and in articular inflammatory processes.

PMID- 7520501
TI  - Probenecid inhibits transforming growth factor-beta 1 induced pyrophosphate
      elaboration by chondrocytes.
AB  - OBJECTIVE: The elaboration of excess extracellular inorganic pyrophosphate (ePPi)
      by cartilage contributes to calcium pyrophosphate dihydrate (CPPD) crystal
      deposition disease. Transforming growth factor-beta 1 (TGF beta 1) is the only
      defined physiologic stimulant of cartilage ePPi elaboration. The mechanism of
      ePPi generation by chondrocytes is unknown, but current evidence suggests that
      TGF beta 1 induced ePPi is made intracellularly. An active transport mechanism
      such as an anion transporter would then be necessary to export ePPi to the matrix
      where crystals form. We determined the effect of probenecid (PB), an anion
      transport inhibitor, on TGF beta 1 induced ePPi elaboration. METHODS: Porcine
      hyaline articular chondrocytes in high density monolayer cultures were exposed to
      serum-free media with and without TGF beta 1 and/or PB. ePPi was measured in the
      media after 48-96 h of exposure. Cell injury was measured by examining the
      release of 3H-deoxyglucose from chondrocytes. The activity of the ePPi generating
      ectoenzyme nucleoside triphosphate pyrophosphohydrolase (NTPPPH) and media
      lactate concentrations were measured with standard colorimetric assays. As PB may
      inhibit phosphodiesterase (PDE), its effects on ePPi generation were compared
      with isobutylmethylxanthine (IBMX), a specific PDE inhibitor. RESULTS: PB
      inhibited TGF beta 1 induced ePPi elaboration by chondrocytes. PB did not cause
      membrane injury or decrease NTPPPH activity. Lactate production was decreased by
      PB but did not correlate with the effects of PB on ePPi elaboration. IBMX did not
      inhibit TGF beta 1 effect on ePPi elaboration. CONCLUSION: PB blocks TGF beta 1
      induced ePPi elaboration. This effect is independent of cell membrane injury,
      decreased NTPPPH activity, or PDE inhibition. Our data implicate a role for anion
      transport in TGF beta 1 induced ePPi elaboration, and suggest a potential therapy
      for CPPD disease.

PMID- 7520502
TI  - Regulation of gap junctional coupling in isolated pancreatic acinar cell pairs by
      cholecystokinin-octapeptide, vasoactive intestinal peptide (VIP) and a VIP
      antagonist.
AB  - Cholecystokinin-octapeptide (CCK-OP) induces a time- and dose-dependent decrease
      of gap junctional conductance in isolated pairs of pancreatic acinar cells. In
      double whole-cell experiments, the time course could be described by the latency
      and the half-life time (t1/2) of cell-to-cell uncoupling. The latency shows a
      biphasic dependence on [CCK-OP] with a minimum of about 50 sec at 10(-9) M CCK
      OP. In the presence of vasoactive intestinal peptide (VIP), the biphasic
      relationship is shifted to lower CCK-OP concentrations. The increase of latency
      at high concentrations of CCK-OP (> 10(-9) M) was blocked by addition of a VIP
      antagonist. t1/2 decreases monophasically with increasing [CCK-OP]. Addition of
      GTP gamma S to the pipette solution suppresses the [CCK-OP] dependence of the
      latency and potentiates the uncoupling phase. The kinetic data are discussed in
      terms of CCK binding to receptors of high and low affinity. Evidence is presented
      that secretion and cell-to-cell coupling are not related by an all-or-none
      process, but that for physiological CCK-OP concentrations, gap junctional
      uncoupling follows secretion.

PMID- 7520504
TI  - Conformation of the central, three-helix junction of the 5 S ribosomal RNA of
      Sulfolobus acidocaldarius.
AB  - The current investigation has focused on the structure of the central, three
      helix junction of the 5 S ribosomal RNA from Sulfolobus acidocaldarius, a
      thermoacidophilic archaebacterium. The 5 S molecule from S. acidocaldarius
      represents a paradigm for the study of the 5 S junction (and branched RNA
      structures in general) due to its unusually high degree of predicted secondary
      structure and stability. In order to study the junction in isolation, a set of
      three RNA heteroduplex molecules was assembled in which pairs of helices bounding
      the junction were extended by 70 base-pairs per helix. Since the extended helices
      comprise more than 95% of the heteroduplex structure, the relative solution
      conformations of the heteroduplex molecules, in effect, "report" the interhelix
      (branch) angles bounded by the extended pairs of helices. Examination of these
      heteroduplex molecules, using a combination of gel electrophoresis and transient
      electric birefringence measurements, has revealed a tertiary structure for the
      central branch in which helices I and V are essentially collinear, and in which
      helix II is relatively free to reorient with respect to the I-V axis.

PMID- 7520505
TI  - Polypeptide conformational space. Dynamics by solution NMR disorder by X-ray
      crystallography.
AB  - A symmetric dimer of a polypeptide in an organic solvent is shown to be a useful
      molecular system for observing the effects of crystal packing and solution
      dynamics on structure determination by X-ray crystallography and solution NMR
      methods. Organic solvents are not ideal models of a lipid environment, but they
      represent a better model environment than does water, in fact, for modeling some
      properties of the lipid environment, organic solvents work very well. In
      particular, it is a good model for assessing the influence of lipids on local
      polypeptide dynamics and conformational rearrangements. The solution NMR
      structure of gramicidin in the mixed solvent of benzene and ethanol is compared
      to the crystal structure formed from a benzene/ethanol azeotrope. High resolution
      structural characterization leads to unique correlations of disorder in the
      crystal to dynamics in solution. Furthermore, crystal packing effects lead to
      significant asymmetries in both the polypeptide backbone and in the side-chains.

PMID- 7520503
TI  - Transcription activation by the Escherichia coli cyclic AMP receptor protein.
      Receptors bound in tandem at promoters can interact synergistically.
AB  - Starting with a semi-synthetic Escherichia coli promoter with a binding site for
      the cyclic AMP receptor protein (CRP) centred between base-pairs 41 and 42
      upstream from the transcription start site, a second upstream CRP-binding site,
      centred between base-pairs 90 and 91, was introduced. CRP binding to this second
      upstream site results in a several-fold greater stimulation of CRP-dependent
      transcription initiation, compared to activation at the starting promoter with
      just one CRP-binding site. Activation of transcription by the upstream CRP
      molecule is blocked by the HL159 substitution, suggesting that the upstream-bound
      CRP makes a direct contact with RNA polymerase. Footprinting experiments suggest
      that RNA polymerase contacts the promoter DNA between the two CRP-binding sites,
      most likely due to interactions involving the C-terminal part of the alpha
      subunit. Synergy between tandem bound CRP molecules in transcription activation
      requires that the two CRP-binding sites be separated by around 40 or 50 base
      pairs, but is not found at intermediate spacings. An experiment in which the
      upstream CRP-binding site is replaced by a site for the related transcription
      factor, FNR, shows that heterologous synergistic interactions between FNR and CRP
      are possible.

PMID- 7520506
TI  - Pattern generation in molecular evolution: exploitation of the variation in RNA
      landscapes.
AB  - Evolution of RNA secondary structure is studied using simulation techniques and
      statistical analysis of fitness landscapes. The transition from RNA sequence to
      RNA secondary structure leads to fitness landscapes that have local variations in
      their "ruggedness." Evolution exploits these variations. In stable environments
      it moves the quasispecies toward relatively "flat" peaks, where not only the
      master sequence but also its mutants have a high fitness. In a rapidly changing
      environment, the situation is reversed; evolution moves the quasispecies to a
      region where the correlation between secondary structures of "neighboring" RNA
      sequences is relatively low. In selection for simple secondary structures the
      movement toward flat peaks leads to pattern generation in the RNA sequences.
      Patterns are generated at the level of polynucleotide frequencies and the
      distribution of purines and pyrimidines. The patterns increase the modularity of
      the sequence. They thereby prevent the formation of alternative secondary
      structures after mutations. The movement of the quasispecies toward relatively
      rugged parts of the landscape results in pattern generation at the level of the
      RNA secondary structure. The base-pairing frequency of the sequences increases.
      The patterns that are generated in the RNA sequences and the RNA secondary
      structures are not directly selected for and can be regarded as a side effect of
      the evolutionary dynamics of the system.

PMID- 7520508
TI  - Altered angiogenesis underlying age-dependent changes in tumor growth.
AB  - BACKGROUND: Cancer incidence increases with age, but the growth and spread of
      tumors is often slow and prolonged in the elderly. Transplantable murine tumors
      grow and spread less readily in older mice and can be used as models to study the
      effect of host age. Neovascularization is crucial for the growth of solid tumors,
      and alterations in the host vascular response may underlie the changes in tumor
      growth occurring with age. PURPOSE: We have used transplantable tumor cells and
      tumors, and tumor extracts, to better understand differences in the biology of
      tumor growth and vascularization as a function of host age. METHODS: Englebreth
      Holm-Swarm (EHS) carcinoma and B16-F10 melanoma cells were injected into C57BL
      mice of different ages. Tumor growth, histology, and cellular DNA synthesis were
      compared. Vascularization was determined using basic fibroblast growth factor and
      an in vivo angiogenesis assay. EHS tumor extracts were assayed for biologic
      activity in vitro using human endothelial cells and in vivo using mouse EHS-BAM
      carcinoma and human TSU-Pr1 prostate carcinoma cells. RESULTS: EHS tumors formed
      larger tumors in young than in old C57BL mice. Rapid tumor growth resumed upon
      transfer of tumor tissue from old animals into young animals. The rate of DNA
      synthesis of tumor tissue from old animals in organ culture was lower than in
      tissue from young animals. Histologically, tumors grown in old animals exhibited
      a threefold higher ratio of extracellular matrix to tumor cells than those grown
      in young animals. Tumors from adult animals exhibited numerous small blood
      vessels; those from old animals contained fewer, much larger vessels. Similar
      results were observed in young mice fed a reduced-calorie diet. Young animals
      elicited a greater and more rapid angiogenic response than old animals. Extracts
      of tumors grown in old animals failed to support endothelial cell differentiation
      in culture. Tumor cells injected together with such old extracts showed reduced
      tumor growth in nude mice. CONCLUSIONS: The rate of growth and morphology of the
      EHS tumor were altered with age, partly due to a reduced capacity to vascularize
      the tumors because of a lack of angiogenic factors or the presence of host
      inhibitors. IMPLICATIONS: Alterations in host factors detected in this tumor
      model may underlie a variety of age-dependent changes that could influence tumor
      growth and the repair and regeneration of normal tissue. Reducing the
      vascularization of tumors represents a potential target to reduce their growth
      and progression.

PMID- 7520507
TI  - Interactive technology enters realm of cancer education.

PMID- 7520509
TI  - Benign prostatic hyperplasia: diagnosis and treatment. Guideline overview. Agency
      for Health Care Policy and Research.

PMID- 7520510
TI  - Effects of the short-chain triglyceride triacetin on intestinal mucosa and
      metabolic substrates in rats.
AB  - Diets containing either triacetin (the water-soluble triglyceride of acetate) or
      long-chain triglycerides (LCTs) were fed to rats to determine the effects on
      intestinal mucosa cells and plasma substrates. Male Sprague-Dawley rats were fed
      one of three diets, a control diet containing 5% of energy as LCTs or one of two
      experimental diets that contained 30% of energy as lipid. The lipid component of
      the two experimental diets was either 100% LCTs or 95% triacetin/5% LCTs. Plasma
      lactate, glucose, and total ketone body concentrations were not significantly
      different among dietary treatment groups. Compared with animals fed LCTs and
      control diet, plasma pyruvate and free fatty acid concentrations were decreased
      in animals fed triacetin. In contrast, plasma triglyceride concentrations were
      elevated in animals fed triacetin compared with other groups. Intestinal
      biochemical measures included total DNA, RNA, protein, and the protein:DNA ratio.
      Histologic indices measured were villus height in the jejunum and crypt depth in
      the colon. No significant difference in mucosal protein concentration was
      observed in the jejunum and colon. Jejunal RNA was significantly decreased in
      animals fed triacetin compared with other diets. Triacetin feeding significantly
      increased the DNA content in the jejunum and colon (thereby lowering the
      protein:DNA ratio), indicating smaller, more numerous cells. Jejunal villus
      height and colonic crypt depth were not significantly different among dietary
      treatment groups. Provision of a balanced diet containing 28.5% of the total
      calories as triacetin had no adverse effects on metabolic substrates and resulted
      in smaller and more numerous mucosal cells in the jejunum and colon.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7520511
TI  - [Quantitative flow-cytometric analysis of CD34-positive stem cells in peripheral
      blood stem cell harvests].
AB  - The percentage of CD34-positive cells (the CD34-positive rate) in peripheral
      blood stem cell harvests (PBSCH) was determined using two color flow cytometric
      methods, i.e., representation in a histogram (the histogram method) and the two
      dimensional side scatter-fluorescence representation (the SSC-FL method). For all
      samples examined, the CD34-positive rate obtained using the histogram method was
      higher than that obtained using the SSC-FL method. This finding was probably due
      to the fact that some monocytes non-specifically reacted with anti-CD34
      monoclonal antibody, and the histogram method could not distinguish these non
      specifically stained cells from CD34-positive precursor cells. On the other hand,
      the SSC-FL method seemed to yield a more accurate measurement of the percentage
      of CD34-positive cells in PBSCH samples. Based on this finding, it is recommended
      that the histogram method, which is currently used at most commercial
      laboratories, be reviewed in favor of the SSC-FL method when the CD34-positive
      cell rate of PBSCH is to be determined.

PMID- 7520512
TI  - [CD7 positive undifferenciated leukemia/lymphoma associated with leukemic
      pericarditis].
AB  - We report here a CD7 positive undifferenciated leukemia/lymphoma which showed a
      rapid clinical course. A 27-year-old female was complained of palpitation and
      edema. She had a mediastinal tumor and pericardial effusion. Lymphoblastic cells
      were found in the effusion, but in the peripheral blood initially. After
      admission the blast cells appeared in the peripheral blood, and they were
      revealed negative for peroxidase and had phenotype of CD7 and CD33 positive. The
      patient suffered from cardiac tamponade and died 15 days after admission. The
      Southern blotting of mediastinal tumor cells disclosed the germline configuration
      for TCR-beta a chain and the rearrangement of immunoglobulin heavy chain genes.

PMID- 7520513
TI  - [Vitronectin in plasma and colonic mucosa of patients with ulcerative colitis].
AB  - Plasma levels and localization of vitronectin in patients with ulcerative colitis
      (UC) were investigated. Plasma vitronectin levels in patients with UC were
      significantly lower than those of healthy persons, in proportion to clinical
      activity and severity. In addition, plasma vitronectin levels at the remission
      phase were high when compared with those at the active phase. Vitronectins, in
      addition, were found in mucosa of the active phase where a lot of inflammatory
      cells were found by immunohistological staining. Based on the above results,
      vitronectins were considered to leak from blood vessel and to be consumed for
      mucosa recovery in the active phase of UC, and plasma vitronectin levels were
      lowering. Therefore, determination of plasma vitronectin levels were considered
      to be useful for an index of clinical activity and severity of patients with UC.

PMID- 7520514
TI  - [Adrenal cyst with an immunohistochemical evidence of mesothelial origin. Report
      of a case].
AB  - A case of adrenal cyst with an immunohistochemical evidence of mesothelial origin
      is presented. A 73-year-old Japanese woman was referred to our hospital with a
      complaint of left flank pain. The diagnosis of left adrenal cyst was made based
      on the radiographic and hormonal examinations. The adrenal cyst was removed
      surgically. Histological examination revealed that the cyst was lined with either
      a single layer of squamous or cuboidal cells. In immunohistochemistry testing,
      the cells were positive for keratin and carbohydrate antigen 125, while they were
      negative for epithelial membrane antigen, vimentin, desmin, and factor VIII
      related antigen. Thus, the present case was classified as epithelial cyst of
      mesothelial origin.

PMID- 7520515
TI  - [Granulocyte function of patients on anti-cancer chemotherapy].
AB  - Granulocyte function of patients on anti-cancer chemotherapy was investigated.
      Five bladder cancer patients, who had undergone M-VAC neo-adjuvant, chemotherapy
      were select for this study. Their tumor stage was T3M0N0 and peripheral blood
      granulocyte and platelet counts were more than 1500/mm3 and 10 x 10(4)/mm3,
      respectively, before starting chemotherapy regardless of the course Flow
      cytometric analyses were utilized to measure the function of phagocytosis and the
      ability to produce superoxide (bactericidal function) of granulocytes. During the
      course peripheral blood count, granulocyte function, urinalysis and blood
      chemistry were checked every other day and urine and blood culture were done once
      a week. Although the first course of M-VAC was completed without using rhG-CSF,
      the second course of M-VAC administration required rhG-CSF when the number of
      peripheral granulocytes was below 1000/mm3. The function of phagocytosis
      decreased from the onset of the first course of M-VAC until the nadir of
      granulocyte number, then recovered close the pre-chemotherapy level by the time
      when the chemotherapy was completed with the increase in the number of
      granulocyte but remained relatively low until starting the second course. The
      function deteriorated more rapidly with the second course than with the first
      course, but recovered rapidly after administration of rhG-CSF and was
      significantly higher when the nadir of granulocytes was noted with the first
      course of M-VAC than with the second course. As for the function of superoxide
      production, it decreased gradually until the nadir of granulocyte during the
      first course and then continued to recover toward starting the second course but
      failed to return to the pre-chemotherapy level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520516
TI  - Hydromorphone and hydrocodone interference in GC/MS assays for morphine and
      codeine.
AB  - The specificity of a GC/MS assay of morphine and codeine was examined with
      particular regard to the potential interference due to hydromorphone and
      hydrocodone, compounds that cross-react extensively in opiate screening tests. A
      GC/MS method with solid-phase extraction and acetylation or trimethylsilylation
      was used. The equilibrium between keto and enol forms of the potential
      interferents was evaluated. Sodium borohydride was tried as a means for
      converting potential interferents into products that are more clearly separated
      from morphine and codeine. It was found that borohydride reduction proceeded
      easily and led to products that could be distinguished from morphine and codeine.
      Moreover, the quantitation of morphine in the presence of hydromorphone was
      improved if the borohydride step was included in the analysis.

PMID- 7520518
TI  - Prevention of long crystal formation in myeloperoxidase staining.

PMID- 7520517
TI  - Interferon-alpha-2b downregulation of oncogenes H-ras, c-raf-2, c-kit, c-myc, c
      myb and c-fos in ESKOL, a hairy cell leukemic line, results in temporal
      perturbation of signal transduction cascade.
AB  - ESKOL, a B-lymphoblastoid cell line consisting of late differentiated cells,
      resembles hairy cell leukemia (HCL). It is pseudodiploid with a deleted 7q and an
      unbalanced translocation between chromosomes 4 and 6. It was screened by Northern
      hybridization for oncogenes, including H-ras, c-raf-2 (c-raf1p1), c-kit, c-myc, c
      myb, c-fos, Fim-1, c-jun, ski, and c-mos, which are believed to contribute to B
      cell differentiation and maturation. Interferon-alpha-2b (IFN) downregulates the
      expression of H-ras, c-raf-2, c-kit, c-myc, c-myb, c-fos, as determined by
      Northern hybridization of RNA isolated from cells harvested at time points during
      a 30 h time course. Downregulation of oncogenes H-ras, c-raf-2, c-kit, whose
      proteins are associated with cell surfaces or are cytosolar transducers, occurs
      before those oncogenes c-myc, c-myb, and c-fos, whose products are DNA binding
      proteins. This suggests a temporal perturbation of signal transduction by IFN. No
      change in oncogene expression occurred in non-treated cells nor were these
      oncogenes expressed in the non-transformed B-lymphoblast cell line, Wil-2, under
      the same treatment regimen. The basis for the IFN perturbation is not understood;
      yet the role of these oncogenes as signal transducers in differentiation and
      proliferation of human hematopoietic progenitors is unfolding, and ESKOL is an
      excellent system in which to study this phenomenon.

PMID- 7520519
TI  - The coming of age of serologic testing for anti-neutrophil cytoplasmic
      autoantibodies.

PMID- 7520520
TI  - Point mutation in platelet mitochondrial tRNA(Leu(UUR)) in patient with cluster
      headache.

PMID- 7520521
TI  - Nitric oxide- and hydrogen peroxide-mediated gene expression by glucocorticoids
      and FK506 in histamine paw edema of mice.
AB  - An immunosuppressant FK506 binds with a component (hsp 56) of glucocorticoid
      receptor (GR) complex. Dexamethasone (Dex) never suppressed histamine paw edema
      of mice before 1 hr after its dosing as new protein(s) synthesis is required.
      However, FK506 (0.01-10 mg/kg, oral) 1.5 hr before 0.1 mg/kg Dex (s.c.),
      suppressed edema at 30 min. This suppression and that at 3 hr, were abolished by
      nitric oxide (NO) synthesis inhibitors (1-300 mg/kg). Nitroprusside (NO donor),
      catalase and molybdate (GR complex stabilizing protease inhibitor) enhanced the
      suppression. FK506, not cyclosporin A, was demonstrated for the first time in
      vivo to enhance GR and a hypothesis is proposed that FK506 might enhance GR and
      AP-1 signalings in a system reciprocally controlled by NO and H2O2.

PMID- 7520522
TI  - Intrafamily spread of hepatitis C virus infection.
AB  - Using the second generation ELISA test, we studied the prevalence of antibodies
      against hepatitis C virus (anti-HCV) among 159 household contacts of 86 anti-HCV
      positive subjects (index cases). Fourteen (8.8%) relatives were found anti-HCV
      positive, a rate higher than the corresponding figure reported among the general
      population in the same area. The prevalence of anti-HCV was significantly higher
      among sexual partners than among household contacts without sexual relations with
      the index case (18% vs. 3.1%; P < 0.01). These findings indicate that sexual
      transmission may be the main route for intrafamily HCV spread.

PMID- 7520523
TI  - Shc, Grb2, Sos1, and a 150-kilodalton tyrosine-phosphorylated protein form
      complexes with Fms in hematopoietic cells.
AB  - Fms, the macrophage colony-stimulating factor (M-CSF) receptor, is normally
      expressed in myeloid cells and initiates signals for both growth and development
      along the monocyte/macrophage lineage. We have examined Fms signal transduction
      pathways in the murine myeloid progenitor cell line FDC-P1. M-CSF stimulation of
      FDC-P1 cells expressing exogenous Fms resulted in tyrosine phosphorylation of a
      variety of cellular proteins in addition to Fms. M-CSF stimulation also resulted
      in Fms association with two of these tyrosine-phosphorylated proteins, one of
      which was identified as the 55-kDa Shc, which is shown in other systems to be
      involved in growth stimulation, and the other was a previously uncharacterized
      150-kDa protein (p150). Fms also formed complexes with Grb2 and Sos1, and neither
      contained phosphotyrosine. Whereas both Grb2 and Sos1 complexed with Fms only
      after M-CSF stimulation, the amount of Sos1 complexed with Grb2 was not M-CSF
      dependent. Shc coimmunoprecipitated Sos1, Grb2, and tyrosine-phosphorylated p150,
      while Grb2 immunoprecipitates contained mainly phosphorylated p150, Fms, Shc, and
      Sos1. Shc interacted with tyrosine-phosphorylated p150 via its SH2 domain, and
      the Grb2 SH2 domain likewise bound tyrosine-phosphorylated Fms and p150. Analysis
      of Fms mutated at each of four tyrosine autophosphorylation sites indicated that
      none of these sites dramatically affected p150 phosphorylation or its association
      with Shc and Grb2. M-CSF stimulation of fibroblast cell lines expressing
      exogenous murine Fms did not phosphorylate p150, and this protein was not
      detected either in cell lysates or in Grb2 or Shc immunoprecipitates. The p150
      protein is not related to known signal transduction molecules and may be myeloid
      cell specific. These results suggest that M-CSF stimulation of myeloid cells
      could activate Ras through the nucleotide exchange factor Sos1 by Grb2 binding to
      either Fms, Shc, or p150 and that Fms signal transduction in myeloid cells
      differs from that in fibroblasts.

PMID- 7520524
TI  - Cooperativity between two NF-kappa B complexes, mediated by high-mobility-group
      protein I(Y), is essential for cytokine-induced expression of the E-selectin
      promoter.
AB  - Cytokine-induced expression of the E-selectin gene requires the promoter binding
      and interaction of the transcription factors NF-kappa B and ATF. Here we have
      further analyzed the E-selectin promoter and revealed an additional region
      (nucleotides -140 to -105 [-140/-105]) which is essential in controlling promoter
      activation by cytokines. We identified high-mobility-group protein I(Y) [HMG
      I(Y)] interacting specifically at two sites within this region. We noted that one
      of the HMG-I(Y)-binding sites overlaps a sequence element (-127/-118) diverging
      at only one position from the NF-kappa B consensus binding sequence. This led us
      to ask whether the -127/-118 element represents a second functional NF-kappa B
      binding site within the E-selectin promoter. Using specific antisera, we show
      that p50, p65, and, interestingly, RelB are components of the complex interacting
      at this site. Mutational analysis of the -127/-118 NF-kappa B site indicates that
      both NF-kappa B and HMG-I(Y) binding at this site are essential for interleukin-1
      induction of the promoter. We demonstrate that the binding affinity of the p50
      subunit of NF-kappa B to both NF-kappa B sites within the E-selectin promoter is
      significantly enhanced by HMG-I(Y). In addition, an essential role for
      cooperative interaction between the two NF-kappa B complexes is shown by the
      requirement for both NF-kappa B sites to mediate E-selectin promoter activation
      by interleukin-1 and p50/p65 expression. We conclude that HMG-I(Y) mediates
      binding of a distinct NF-kappa B complex at two sites within the E-selectin
      promoter. Furthermore, a unique cooperativity between these NF-kappa B complexes
      is essential for induced E-selectin expression. These results suggest mechanisms
      by which NF-kappa B complexes are involved in specific gene activation.

PMID- 7520526
TI  - Three NF-kappa B binding sites in the human E-selectin gene required for maximal
      tumor necrosis factor alpha-induced expression.
AB  - Transcription of the gene encoding the endothelial cell-leukocyte adhesion
      molecule (ELAM-1; E-selectin) is induced in response to various cytokines,
      including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1. A DNase I
      hypersensitive site in the 5' proximal promoter region of the E-selectin gene is
      observed in human umbilical vein endothelial cells only following TNF-alpha
      treatment, suggesting the presence of a TNF-alpha-inducible element close to the
      transcriptional start site. Transient transfection studies in endothelial cells
      demonstrated that 170 bp of upstream sequences is sufficient to confer TNF-alpha
      inducibility. Systematic site-directed mutagenesis of this region revealed two
      regulatory elements (-129 to -110 and -99 to -80) that are essential for maximal
      promoter activity following cytokine treatment. Protein binding studies with
      crude nuclear extracts and recombinant proteins revealed that the two elements
      correspond to three NF-kappa B binding sites (site 1, -126; site 2, 116; and site
      3, -94). All three sites can be bound by NF-kappa B when used as independent
      oligonucleotides in mobility shift assays. However, within the context of a
      larger promoter fragment, sites 2 and 3 are preferentially occupied over site 1.
      These data are consistent with results obtained in transfection studies
      demonstrating that mutations in sites 2 and 3 are more detrimental than mutations
      within site 1. Hence, inducibility of the E-selectin gene requires the
      interaction of NF-kappa B proteins bound to multiple regulatory elements.

PMID- 7520525
TI  - Ty1 in vitro integration: effects of mutations in cis and in trans.
AB  - Mutations within the TYB gene of Ty1 encoding integrase (IN) as well as
      alterations in its substrate, a linear DNA molecule, were examined for their
      effects on in vitro IN activity, using a recently developed physical assay. Five
      different codon-insertion mutations, two frameshift mutations, and one missense
      mutation, previously identified as transposition-deficient mutations, were
      tested. Virus-like particles, the source of IN, from two different protease
      mutants and a reverse transcriptase mutant exhibited near-normal to normal IN
      activity. Two frameshift mutations mapping within the phylogenetically variable C
      terminal domain of IN resulted in significant in vitro IN activity. In contrast,
      three mutations within the amino-terminal conserved domain of IN completely
      abolished IN activity. When the substrate termini were mutated, we found that
      substrates with as few as 4 bp of Ty1 termini were capable of efficiently
      generating integration products. Surprisingly, certain substrates that lacked
      obvious similarity to Ty1 termini were also readily integrated into both linear
      and circular targets, whereas others were not used as substrates at all. Termini
      rich in adenosine residues were among the more active substrates; however,
      certain substrates lacking terminal adenosine residues can form small quantities
      of integration products, including complete integration reactions.

PMID- 7520527
TI  - A role for RNA synthesis in homologous pairing events.
AB  - The relationship between RNA synthesis and homologous pairing in vitro, catalyzed
      by RecA protein, was examined by using an established strand transfer assay
      system. When a short DNA duplex is mixed with single-stranded circles, RecA
      protein promotes the transfer of the minus strand of the duplex onto the
      complementary region of the plus-strand circle, with the displacement of the plus
      strand of the duplex. However, if minus-strand RNA is synthesized from the duplex
      pairing partner, joint molecules containing the RNA transcript, the plus strand
      of the DNA duplex, and the plus-strand circle are also observed to form. This
      reaction, which is dependent on RNA polymerase, sequence homology, and RecA
      protein, produces a joint molecule that can be dissolved by treatment with RNase
      H but not RNase A. Under these reaction conditions, product molecules form even
      when the length of shared homology between duplex and circle is reduced to 15 bp.

PMID- 7520528
TI  - Physical and functional interactions between SH2 and SH3 domains of the Src
      family protein tyrosine kinase p59fyn.
AB  - The Src family protein tyrosine kinases participate in signalling through cell
      surface receptors that lack intrinsic tyrosine kinase domains. All nine members
      of this family possess adjacent Src homology (SH2 and SH3) domains, both of which
      are essential for repression of the enzymatic activity. The repression is
      mediated by binding between the SH2 domain and a C-terminal phosphotyrosine, and
      the SH3 domain is required for this interaction. However, the biochemical basis
      of functional SH2-SH3 interaction is unclear. Here, we demonstrate that when the
      SH2 and SH3 domains of p59fyn (Fyn) were present as adjacent domains in a single
      protein, binding of phosphotyrosyl peptides and proteins to the SH2 domain was
      enhanced, whereas binding of a subset of cellular polypeptide ligands to the SH3
      domain was decreased. An interdomain communication was further revealed by
      occupancy with domain-specific peptide ligands: occupancy of the SH3 domain with
      a proline-rich peptide enhanced phosphotyrosine binding to the linked SH2 domain,
      and occupancy of the SH2 domain with phosphotyrosyl peptides enhanced binding of
      certain SH3-specific cellular polypeptides. Second, we demonstrate a direct
      binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases.
      Heterologous binding between SH2 and SH3 domains of closely related members of
      the Src family, namely, Fyn, Lck, and Src, was also observed. In contrast, Grb2,
      Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2
      domains showed lower or no binding to Fyn or Lck SH3 domains. SH2-SH3 binding did
      not require an intact phosphotyrosine binding pocket on the SH2 domain; however,
      perturbations of the SH2 domain induced by specific high-affinity phosphotyrosyl
      peptide binding abrogated binding of the SH3 domain. SH3-SH2 binding was observed
      in the presence of proline-rich peptides or when a point mutation (W119K) was
      introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although
      these treatments completely abolished the binding to p85 phosphatidylinositol 3
      kinase and other SH3-specific polypeptides. These biochemical SH2-SH3
      interactions suggest novel mechanisms of regulating the enzymatic activity of Src
      kinases and their interactions with other proteins.

PMID- 7520532
TI  - Activity-dependent modulation of excitability: implications for axonal physiology
      and pathophysiology.

PMID- 7520530
TI  - Molecular identification of Rickettsiae.

PMID- 7520531
TI  - Ion channels in a skeletal muscle cell line from a Duchenne muscular dystrophy
      patient.
AB  - A cell line (RCDMD), derived from a muscle biopsy taken from a 7-year-old patient
      with Duchenne muscular dystrophy (DMD), was established in vitro using
      conditioned media from the UCHT1 thyroid cell line as described elsewhere
      (Biochim Biophys Acta 1992; 1134:247-255). Unlike other cell lines established by
      the same procedure, RCDMD cells were highly refractory to transformation and the
      resulting cell line grew slowly with a doubling time of approximately 72 h.
      Further, cells continue to grow after more than 20 doublings and 15 passages.
      Some of the characteristics of the cell line include lack of reaction with
      antidystrophin antibodies and the presence of receptors for the dihydropyridine
      PN200-110 (Kd) = 0.3 +/- 0.05 nmol/L and Bmax = 1.06 +/- 0.03 pmol/mg protein)
      and for alpha-bungarotoxin (Kd = 1.02 +/- 0.17 nmol/L and Bmax = 4.2 +/- 0.37
      pmol/mg protein). Patch clamped cells in the voltage clamp configuration lack ion
      currents when growing in complete medium with high serum, but they can be induced
      to differentiate by serum deprivation and addition of hormones and trace
      elements. After 5 days in differentiating medium, noninactivating, delayed
      rectifier potassium currents are seen. At day 12, A-type, inactivating potassium
      currents as well as transient inward currents are seen. In conditions in which
      sodium and potassium currents are absent, a very fast activating and fast
      inactivating calcium current was evident. The cell line offers the possibility of
      studying cellular mechanisms in the pathophysiology of DMD.

PMID- 7520533
TI  - School-age outcomes in children with birth weights under 750 g.
AB  - BACKGROUND: Since the mid-1980s, increasing numbers of children with birth
      weights under 750 g have survived to school age. METHODS: We matched a regional
      cohort of 68 surviving children born from 1982 through 1986 with birth weights
      under 750 g (mean, 670 g; gestational age, 25.7 weeks) with 65 children weighting
      750 to 1499 g at birth and 61 children born at term. Growth, neurosensory status,
      and functioning at school age in the three groups were compared. Associations of
      biologic and social risk factors with major developmental outcomes were examined
      by means of logistic-regression analyses. RESULTS: Children with birth weights
      under 750 g were inferior to both comparison groups in cognitive ability,
      psychomotor skills, and academic achievement. They had poorer social skills and
      adaptive behavior and more behavioral and attention problems. The mean (+/- SD)
      Mental Processing Composite score for the cohort was 87 +/- 15, as compared with
      93 +/- 14 for children with birth weights of 750 to 1499 g and 100 +/- 13 for
      children born at term (P < 0.001). The rates of mental retardation (IQ < 70) in
      the three groups were 21, 8, and 2 percent, respectively; the rates of cerebral
      palsy were 9, 6, and 0 percent; and the rates of severe visual disability were
      25, 5, and 2 percent. Major cerebral ultrasonographic abnormalities were
      associated with mental retardation (odds ratio, 5.4; 95 percent confidence
      interval, 1.8 to 15.8) and cerebral palsy (odds ratio, 15.2; 95 percent
      confidence interval, 3.0 to 77.4). Oxygen dependence at 36 weeks was associated
      with mental retardation (odds ratio, 4.5; 95 percent confidence interval, 1.2 to
      10.7) and severe visual disability (odds ratio, 4.3; 95 percent confidence
      interval, 1.3 to 14.2). Social disadvantage, though associated with several
      neuropsychological outcomes, was not associated with major developmental
      impairment. CONCLUSIONS: Children with birth weights under 750 g who survive
      represent a subgroup of very-low-birth-weight children who are at high risk for
      neurobehavioral dysfunction and poor school performance.

PMID- 7520529
TI  - Structure of the murine CD40 ligand gene.
AB  - The mouse CD40 ligand (CD40L) gene was cloned, sequenced and characterized. DNA
      sequence analysis showed that the CD40L gene comprises five exons and four
      intervening introns, spread over 13-14 kb of genomic DNA. The putative site for
      initiation of mRNA transcription was identified at 67 bp upstream of the
      translation initiation (ATG) codon. The nucleotide sequence of the 5'-flanking
      region of this gene revealed the presence of several regulatory regions including
      a TATA-like box, an Sp1-like box and six potential NF-AT-like motifs. The 3'
      untranslated region of the murine CD40L gene contained two ATTTA-elements which
      are thought to confer instability to the mRNA of many cytokines and two adjacent
      dinucleotide repeates, (CT)25 and (CA)45. These elements may play a role in the
      post-transcriptional regulation of CD40L gene expression.

PMID- 7520534
TI  - Gliotoxin inhibits transformation and its cytotoxic to turkey peripheral blood
      lymphocytes.
AB  - Gliotoxin, an epipolythiodioxopiperizine mycotoxin, has been shown to be produced
      by, among other fungi, Aspergillus fumigatus Fresenius. This organism is the
      major causative agent of the respiratory disease aspergillosis in avian species,
      especially turkeys. Because gliotoxin has been shown to be immunosuppressive and
      has the potential for being involved in the pathogenesis of aspergillosis, the in
      vitro activity of this compound with avian lymphocytes was investigated.
      Immunosuppression was investigated using peripheral blood lymphocytes from
      turkeys in a lymphoblastogenesis assay and a cytotoxicity assay using conversion
      of the tetrazolium salt MTT to MTT formazan by the mitochondrial succinate
      dehydrogenase enzyme elaborated only by living cells. Gliotoxin appeared to have
      a threshold level in both tests because little or no response or stimulation was
      evident when cells were exposed to concentrations of the toxin below 100 ng/ml,
      but at 100 ng/ml, all cells appeared to be dead. Using T-2 mycotoxin as a known
      cytotoxic agent, the response in the MTT bioassay using turkey peripheral
      lymphocytes was linear with increasing concentrations of toxin. Gliotoxin may
      potentially cause immunosuppression in turkey poults through action on the
      lymphocytes or if this toxin were present in low concentrations stimulation could
      possibly occur.

PMID- 7520535
TI  - Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic
      pathways.
AB  - The recent generation of perforin knock-out mice has demonstrated a crucial role
      for the pore-forming perforin in cytolytic T-lymphocyte (CTL)-mediated cytolysis.
      Perforin-deficient mice failed to clear lymphocytic choriomeningitis virus in
      vivo, yet substantial killing activity still remained in perforin-free CTLs in
      vitro, indicating the presence of (a) further lytic pathway(s). Fas is an
      apoptosis-signalling receptor molecule on the surface of a number of different
      cells. Here we report that both perforin-deficient and Fas-ligand-deficient CTLs
      show impaired lytic activity on all target cells tested. The killing activity was
      completely abolished when both pathways were inactivated by using target cells
      from Fas-receptor-deficient lpr mice and perforin-free CTL effector cells. Fas
      ligand-based killing activity was triggered upon T-cell receptor occupancy and
      was directed to the cognate target cell. Thus, two complementary, specific
      cytotoxic mechanisms are functional in CTLs, one based on the secretion of lytic
      proteins and one which depends on cell-surface ligand-receptor interaction.

PMID- 7520536
TI  - Effect of Bay K 8644 and ryanodine on the refractory period, action potential and
      mechanical response of the guinea-pig ureter to electrical stimulation.
AB  - We have investigated the effect of the dihydropyridine calcium channel agonist,
      Bay K 8644, and of the plant alkaloid blocker of calcium-induced calcium release
      (CICR) from the sarcoplasmic reticulum, ryanodine, on the refractory period,
      action potential and mechanical response of the guinea-pig isolated ureter to
      electrical stimulation. All experiments were performed in ureters pre-exposed to
      10 microM capsaicin to eliminate the inhibitory influence exerted by local
      release of sensory neuropeptides on ureteral excitability and contraction. In
      organ bath experiments, electrical field stimulation with parameters which
      produce direct excitation of ureteral smooth muscle (train of pulses at 10 Hz, 5
      ms pulse width, 60 V for 1 s) produced tetrodotoxin- (1 microM) resistant phasic
      contractions. The response to EFS was abolished by nifedipine (1 nM-3 microM) and
      was enhanced by Bay K 8644 (1 nM-3 microM). In the presence of Bay K 8644 (1
      microM), nifedipine (30 microM) abolished the evoked contractions. Ryanodine (10
      100 microM) had no significant effect on the amplitude of evoked contraction. The
      response of the guinea-pig ureter to direct electrical stimulation of smooth
      muscle is characterized by a refractory period: at least 40 s interstimulus
      interval was required to produce a second response in all preparations tested.
      Bay K 8644 (1 microM) markedly reduced the refractory period of the ureter and a
      similar effect was observed with ryanodine (100 microM). To further analyze the
      effect of Bay K 8644 and ryanodine on the refractory period, the response of the
      ureter was investigated over a 10 s period of stimulation (other parameters as
      above). In control ureters, continuous stimulation for 10 s produced only one
      phasic contraction just after the beginning of the train of stimuli. In the
      presence of Bay K 8644 or ryanodine, more than one phasic contraction developed
      during a 10 s stimulation, i.e. the refractory period became shorter than the
      train duration. When both Bay K 8644 and ryanodine were tested on the same
      preparations, an additive excitatory effect was observed on the mechanical
      response to electrical stimulation. A slight elevation of KCl concentration (5-10
      mM) reduced the refractory period of the ureter as observed with ryanodine or Bay
      K 8644. Application of KCl (80 mM) produced a biphasic contractile response of
      the ureter: a series of phasic contractions occurred first, which were then
      replaced by a slowly developing tonic response. Bay K 8644 (1 microM) enhanced
      both components of the response to KCl. Ryanodine (10 and 100 microM) markedly
      prolonged the duration of phasic contractions evoked by KCl and, at 100 microM,
      slightly (about 25%) reduced the amplitude of tonic contraction.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7520537
TI  - Increase by NO synthase inhibitors of acetylcholine release from guinea-pig
      myenteric plexus.
AB  - The effects of nitric oxide (NO) synthase inhibitors on the electrically evoked
      release of [3H]acetylcholine were studied in guinea-pig myenteric plexus
      preparations preincubated with [3H]choline. NG-monomethyl-L-arginine (EC50 5.3
      mumol l-1) and NG-nitro-L-arginine (EC50 1.3 mumol l-1) concentration-dependently
      increased the evoked release of [3H]acetylcholine without affecting the basal
      outflow. The facilitatory effect of NG-mono-methyl-L-arginine was prevented by L
      arginine but not by D-arginine. The results suggest that endogenous NO inhibits
      the depolarisation-evoked release of acetylcholine.

PMID- 7520538
TI  - The anticonvulsant effect of citalopram on El mice, and the levels of tryptophan
      and tyrosine and their metabolites in the brain.
AB  - Serotonin(5-HT) plays an important role in the seizures of El mice since the
      seizure threshold of El mice correlates with the 5-HT concentration in the
      central nervous system. In this study, the anticonvulsant effect of a 5-HT
      reuptake blocker, citalopram, was evaluated behaviorally and biochemically. El
      mouse convulsions were inhibited by oral administration of citalopram for 2
      weeks. Citalopram increased tryptophan and tyrosine amounts, and decreased the 5
      HT, 5-hydroxyindoleacetic acid, kynurenine, and dopamine amounts in the brain.
      These findings show that citalopram depresses monoaminergic metabolism. Given the
      known convulsant effect of kynurenine, it is suggested that its decrease by
      citalopram may involve attenuation of El mice seizures.

PMID- 7520540
TI  - Prolonged inhibition of brain nitric oxide synthase by short-term systemic
      administration of nitro-L-arginine methyl ester.
AB  - We studied the dose-response characteristics and the temporal profile of
      inhibition of brain nitric oxide (NO) synthase (NOS) elicited by i.v.
      administration of the NOS inhibitor nitro-L-arginine methyl ester (L-NAME). L
      NAME was administered i.v. in awake rats equipped with a venous cannula. L-NAME
      was injected in cumulative doses of 5, 10, 20 and 40 mg/kg and rats were
      sacrificed 30 min after the last dose. NOS catalytic activity was assayed in
      forebrain cytosol as the conversion of [3H]L-arginine into [3H]L-citrulline. L
      NAME attenuated brain NOS activity in a dose-dependent manner but enzyme activity
      could not be inhibited by more than approximately 50%. After a single 20 mg/kg
      injection of L-NAME the inhibition of brain NOS activity was time dependent and
      reached a stable level at 2 hrs (52% of vehicle). Inhibition after a single
      injection was still present at 96 hrs, albeit to a lower magnitude. We conclude
      that intravenous administration of L-NAME in rats at concentrations commonly used
      in physiological experiments leads to a dose and time-dependent but partial
      inhibition of brain NOS catalytic activity. The finding that the inhibition
      persists for several days after a single administration is consistent with the
      hypothesis that nitro-L-arginine, the active principle of L-NAME, binds to NOS
      irreversibly.

PMID- 7520539
TI  - Glutamate receptor-driven activation of transcription factors in primary neuronal
      cultures.
AB  - We have used primary neuronal cultures prepared from fetal cerebral hemispheres
      to investigate the effects of different glutamate receptor agonists and
      antagonists on the expression of transcription factor encoding genes, such as c
      fos, fosB, c-jun, junB, junD, c-myc, and zif/268. The addition of glutamate (100
      microM) to the culture medium rapidly activated c-fos, fosB, c-jun, junB and
      zif/268 gene expression, reaching the maximal level at 30-60 minutes for zif/268
      and at 60 minutes for the other genes. The onset of fosB mRNA accumulation was
      slightly delayed in comparison to the other genes. No clear induction was found
      for junD and c-myc. Different glutamate receptor agonists, such as NMDA, kainate,
      quisqualate, trans-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) and
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) were able to
      increase c-fos, c-jun, and zif-268 mRNA levels with rapid and transient kinetics
      similar to those observed after glutamate treatment. Similar results were
      obtained for junB and fosB after kainate and quisqualate stimulation.
      Pretreatment with MK-801, a non competitive NMDA antagonist, produced an almost
      complete inhibition of glutamate-driven expression of transcription factor genes,
      thus suggesting that NMDA receptor plays a major role in glutamate induced-gene
      expression. On the contrary the kainate/AMPA receptor antagonist, DNQX, did not
      influence glutamate induced-gene expression. Under the conditions used in the
      present study, NMDA was effective in inducing the simultaneous activation of
      several IEGs even when added to the culture medium containing millimolar
      concentration of magnesium. When experiments were performed in Krebs solution,
      NMDA was effective in stimulating zif/268 and c-fos mRNAs only in the absence of
      Mg2+, while glutamate activated c-fos and zif/268 both in the presence and
      absence of magnesium ions. As expected, NMDA effect was fully inhibited by MK
      801. The level of AP-1 DNA binding activity, as measured by electrophoretic
      mobility shift assay, increased after addition of glutamate and NMDA to cultured
      neurons and such increase was antagonized by the pretreatment with MK-801.

PMID- 7520543
TI  - Intratumoral administration of tumor necrosis factor-alpha for malignant gliomas-
      two case reports.
AB  - Two patients with histologically verified glioblastoma multiforme and anaplastic
      astrocytoma were treated with four courses of intratumoral administration of
      human natural tumor necrosis factor-alpha (TNF) (specific activity 2.0 x 10(6)
      Japan reference unit [JRU]/mg protein) at intervals of 3-5 months. Each consisted
      of eight to 10 serial injections, ranging from 5 x 10(3) to 10(4) JRU/injection,
      at intervals of 3-5 days. There was no simultaneous administration of steroids.
      Serial neurological examinations and neuroimaging studies with computed
      tomography and magnetic resonance imaging demonstrated partial responses ranging
      from 28 and 36 months in duration. No significant TNF-related brain edema,
      intracerebral bleeding, or neurotoxicity occurred. Local immunotherapy with TNF
      may be used safely to contribute to therapeutic efficacy.

PMID- 7520542
TI  - Thermal damage threshold of brain tissue--histological study of heated normal
      monkey brains.
AB  - The thermal damage threshold of normal brain tissue was evaluated from immediate
      and delayed histological changes caused by hyperthermia treatment of normal
      monkey (Macaca fuscata) brains. A 2450 MHz microwave antenna and an antenna
      cooling system devised by our group were used for interstitial hyperthermia
      treatment. The antenna within the cooling system was inserted through a small
      craniectomy under general anesthesia. The temperature at a reference point, 4 mm
      radially away from the surface of the cooling system, was maintained at 42, 43,
      44, 45, or 46 degrees C for 60 minutes. Eighteen animals were treated and
      sacrificed immediately after the treatment, while nine animals were treated and
      sacrificed 7 days after the treatment. The histological changes were studied
      microscopically on sections stained with HE or Kluver-Barrera's method. The non
      survival experiment demonstrated that areas heated at 44 degrees C or below
      showed no obvious irreversible changes. The survival experiment showed areas
      heated at 44 degrees C or above developed coagulative necrosis. These
      histological findings indicate that thermal damage occurs in normal brain tissue
      after heating at 44 degrees C or above for 60 minutes, suggesting that the safety
      limit for brain hyperthermia is 43 degrees C for 60 minutes.

PMID- 7520541
TI  - Kainate binding to the AMPA receptor in rat brain.
AB  - Displacement of [3H]AMPA and [3H]CNQX by kainate was measured in membranes and
      solubilized fractions from rat brain. In soluble fractions, plots of [3H]AMPA and
      [3H]CNQX binding displaced by kainate resulted in one-site fits with Ki values in
      the range of 1-3 microM. In membranes, plots of [3H]AMPA binding displaced by
      kainate resulted in graphs which were better fit by two-site regression analysis
      than by a one-site fit. The Ki value for the high-affinity component of these two
      site fits was 3-9 microM and the low-affinity component Ki was in the range of 70
      120 microM; similar values were determined for kainate displacement of [3H]CNQX.
      The presence of thiocyanate ions had no effect on kainate displacement of
      [3H]CNQX. Since the affinity for kainate of the presumed synaptic AMPA receptor
      is in the range of EC50 values for kainate determined from physiological studies,
      these data contribute further evidence for the idea that kainate binding to
      synaptic AMPA receptors may be responsible for many of kainate's physiological
      effects.

PMID- 7520544
TI  - Familial arteriovenous malformations of the brain--two case reports.
AB  - Familial arteriovenous malformation (AVM) of the brain is an uncommon entity. A
      24-year-old female presented with sudden onset of left hemiparesis due to an AVM
      with a hematoma in the right frontal lobe, which was surgically removed. Her 23
      year-old younger sister presented with motor aphasia and right hemiparesis due to
      an AVM with a hematoma in the left frontoparietal lobes, which was surgically
      removed. Thirty-two patients in 15 families have been described in total. The
      mean age of these patients was 28 years, with 15 males and 17 females. Multiple
      AVMs occurred in four patients (12.5%), more frequently than in non-familial
      cases.

PMID- 7520545
TI  - Cerebellopontine angle meningioma associated with cranial accessory nerve
      neurinoma--case report.
AB  - A 46-year-old female presented with a rare association of cerebellopontine (CP)
      angle meningioma with accessory nerve neurinoma manifesting as headache,
      occasional diplopia, speech disturbance, swallowing difficulty, and unsteady
      gait. Magnetic resonance imaging demonstrated a large tumor in the left CP angle.
      The tumor was totally removed through a lateral suboccipital approach. During the
      operation another smaller tumor was found originating from the cranial accessory
      nerve and was also totally removed. Histological examination found that the
      larger tumor was a meningotheliomatous meningioma and the smaller an Antoni type
      A neurinoma. The symptoms were apparently due to the larger tumor. Careful
      examination of neuroimages is necessary even after the main lesions responsible
      for the symptoms are identified.

PMID- 7520547
TI  - Recurrent malignant histiocytosis with cerebrospinal involvement--case report.
AB  - A 61-year-old male presented with recurrent malignant histiocytosis of the brain
      manifesting as nausea and headache. Malignant histiocytosis is a disorder of
      proliferating histiocytes characterized by a rapidly progressive and fatal
      course, but central nervous system involvement is relatively rare. Magnetic
      resonance (MR) imaging demonstrated cerebrospinal fluid (CSF) dissemination of
      histiocytes as a low-intensity area on the T1-weighted image with marked
      gadolinium-diethylenetriaminepenta-acetic acid enhancement and a high-intensity
      area on the T2-weighted image. CSF cytological examination revealed an increased
      level of atypical histiocytes. Brain and spine irradiation, and intrathecal
      methotrexate and prednisolone administration induced remission. MR imaging is
      particularly useful for the diagnosis of meningeal dissemination of malignant
      histiocytosis.

PMID- 7520548
TI  - Aspergillus brain abscess in a patient with normal immunity--case report.
AB  - A 53-year-old male with normal immunity presented with Aspergillus brain abscess
      manifesting as frontal headache. T2-weighted magnetic resonance imaging revealed
      a hypointense lesion in the left frontal lobe extending into the right frontal
      lobe. The hypointense appearance on T2-weighted images appears to be
      characteristic of aspergillosis. Bifrontal craniotomy exposed an elastic-hard
      mass in the base of the left frontal lobe extending into the right frontal lobe,
      and into the left ethmoid sinus. The mass contained a cavity with white fluid.
      The abscess was removed almost totally. The histological diagnosis was
      Aspergillus abscess. Antibiotic treatment with amphotericin B and fluconazole was
      given for 2 months postoperatively. No recurrence was identified during 15-month
      follow-up.

PMID- 7520546
TI  - Extracranial vertebral artery aneurysm causing spinal subarachnoid hemorrhage-
      case report.
AB  - A 48-year-old female presented with spinal subarachnoid hemorrhage (SAH) due to
      the rupture of an extracranial vertebral artery (VA) aneurysm. The aneurysm arose
      from the junction of the third and the fourth segments of the left VA just inside
      the dura mater, and was partially coated with Biobond. This is only the second
      such case reported. We recommend complete four-vessel angiography in evaluating
      patients with SAH, with special attention given to the extracranial VA if spinal
      SAH is suspected.

PMID- 7520549
TI  - Pediatric cerebellar infarction caused by atlantoaxial subluxation--case report.
AB  - An 11-year-old girl developed cerebellar infarction presenting as a posterior
      fossa mass lesion after stretching and flexing her neck. Cerebral angiography
      demonstrated irregular narrowing of the right vertebral artery at the C2 level
      and x-rays of the upper cervical spine showed atlantoaxial subluxation with os
      odontoideum. She underwent surgical decompression with removal of infarcted
      tissue. The cerebellar infarction probably resulted from occlusion of the
      vertebral artery, followed by brain swelling due to recanalization.

PMID- 7520550
TI  - Primary Ewing's sarcoma of the occipital bone--case report.
AB  - A 12-year-old boy presented with primary Ewing's sarcoma of the occipital bone
      manifesting as intermittent high fever and local pain in the occipital region.
      Plain skull x-ray films disclosed an unclear lytic lesion in the occipital bone.
      Computed tomography and magnetic resonance imaging demonstrated the irregularly
      enhanced mass. The tumor was removed totally. He received intensive chemotherapy
      and radiation therapy postoperatively. No recurrence or metastasis has been
      noted, and he was in good condition 18 months after the operation.

PMID- 7520551
TI  - [Selective problems from catamnestic studies of SSPE patients (1980-1989)].
AB  - The analysis of disease courses and survival times of 132 cases of SSPE treated
      by various methods in the I Department of Neurology, Institute of Psychiatry and
      Neurology, in years 1980-1989 is reported. Follow-up data were obtained during
      control examinations of patients or from an inquiry answered by parents or
      doctors at the place of residence of the patients. In the treatment all patients
      were given immunomodulating drugs. About 25% of the patients were treated with
      isoprinosine, in the remaining groups other drugs active on the immune system
      were added: TFX, alpha interferon (intraventricularly through a Rickham chamber),
      beta interferon (through lumbar tap) or Propionibacterium granulosum strain K 14
      vaccine as an inductor of endogenous interferon. The reference group comprised 22
      patients who had not been systematically treated for various reasons. The
      statistical analysis of the clinical courses showed that early begun
      immunomodulatory treatment increases the number of cases with remissions in the
      group of patients with the subacute form of the disease. In primarily acute cases
      no effect of the treatment was noted. The best results were obtained using
      Propionibacterium granulosum vaccine and treating with interferons. The survival
      times were shortest in the group not treated systematically.

PMID- 7520552
TI  - Differential effects of intrathecally injected galanin on antinociception induced
      by beta-endorphin and morphine administered intracerebroventricularly in mice.
AB  - The effects of intrathecal (i.t.) and intracerebroventricular (i.c.v.) treatments
      with galanin on inhibition of the tail-flick and paw-licking hot-plate responses
      induced by beta-endorphin and morphine administered i.c.v. were studied in ICR
      mice. Galanin (100 ng) given i.t. effectively antagonized inhibition of the tail
      flick response induced by i.c.v. administered beta-endorphin (1 microgram) but
      not morphine (1 microgram). However, the same dose of galanin given i.t. did not
      affect inhibition of the hot-plate response induced by beta-endorphin and
      morphine administered i.c.v. Intrathecal treatment with various doses of galanin
      (0.1-100 ng) dose-dependently antagonized the inhibition of the tail-flick
      response induced by beta-endorphin administered i.c.v. Galanin (100 ng) in
      combination with beta-endorphin (1 microgram) or morphine (1 microgram) given
      i.c.v. did not affect beta-endorphin- or morphine-induced inhibition of the tail
      flick and hot-plate responses. It is concluded that galanin given i.t.
      selectively attenuates i.c.v. beta-endorphin-induced inhibition of the tail-flick
      response by inhibiting descending epsilon-opioid system activated by
      supraspinally applied beta-endorphin.

PMID- 7520554
TI  - Substance P induces biphasic endothelium-dependent relaxations in pig and rabbit
      carotid arteries.
AB  - Careful handling and preparation of freshly harvested vessels from 22 pigs and 12
      rabbits revealed a two-phase vasorelaxation response to cumulative doses of
      substance P (SP). A rapid, transient relaxation was observed during the
      cumulative dose-response and a new plateau of equilibrium was seen following an
      increase in developed force after the last dose of SP. The phase 2 response is
      also produced by submaximal doses of SP and is not altered by pretreatment of the
      rings with Indomethacin. Acetylcholine (ACh) caused an endothelium-dependent
      relaxation but without evidence of a phase 2 plateau. N omega-Nitro-L-Arginine (L
      NNA) and N omega-Nitro-L-Arginine Methylester (L-NAME) pretreatment resulted in a
      shift to the right in the phase 1 response to SP and a complete blockade of phase
      2. Methylene blue caused nearly complete block of both phases. Nitroglycerin
      caused a dose-dependent and prolonged vasorelaxation with no phase 2.

PMID- 7520553
TI  - Detection of immunoreactive substance P-like substances from cat brainstem sites
      during fatiguing isometric contractions.
AB  - Isometric contractions were generated on the left hindlimb muscles from adult
      cats (n = 11) anesthetized with alpha-chloralose (75 mg/kg) to determine whether
      immunoreactive substance P (irSP) was released from either the right
      periaqueductal grey (PAG) or ventrolateral medulla (VLM), sites shown to be
      involved with the integration of the muscle pressor response. The release of
      immunoreactive SP was measured using SP antibody-coated microelectrodes that were
      inserted into the PAG or the VLM during periods of rest, fatiguing isometric
      contractions and post-contraction. Mean arterial pressure increased by 78 +/- 11
      mmHg during the contractions. There was a release of irSP from sites in the
      medulla during the contractions compared to the non-contraction periods but none
      was detected from the PAG in response to muscle stimulation. These results
      provide further evidence that SP-like substances may be involved with the central
      integration of the muscle pressor response.

PMID- 7520557
TI  - The potential role of basophilic leukocytes and mast cells.

PMID- 7520555
TI  - [News in topical antiviral therapy].

PMID- 7520556
TI  - Hypersensitivity reactions during haemodialysis: the choice of methods and
      assays.
AB  - Our considerations about assays to assess agents and mechanisms involved in
      hypersensitivity reactions can be summarized as follows. The measurement of total
      IgE is recommended since it confirms a history of atopy of the patient and is a
      quick and inexpensive laboratory assay. If, based on the anamnesis, a particular
      allergen can be suspected to be involved in the clinical reaction a RAST against
      this compound is highly recommended. In any case of a severe clinical reaction
      the RAST against ethylene oxide is mandatory to confirm or exclude the
      involvement of ethylene oxide. The radioallergosorbent test (RAST) should not be
      used as a screening test for an entirely unknown allergen. The determination of
      histamine in plasma samples can be applied for specific scientific questions but
      cannot be recommended as a routine test with first priority. In contrast, the
      measurement of bradykinin should be established as soon as possible as a routine
      test for all new materials which are developed for application in the
      extracorporeal circuit. An initiative of the haemodialysis community is
      recommended to assure the commercial availability of a reliable bradykinin
      immunoassay.

PMID- 7520561
TI  - Everything you ever wanted to know about your dues but never had time to ask.

PMID- 7520559
TI  - Conditioning yourself for a successful future in dentistry.

PMID- 7520560
TI  - PDA comments on Pennsylvania Health Security Act.

PMID- 7520562
TI  - LHGI/R cement: a restorative dentistry renaissance.

PMID- 7520563
TI  - Managing cancer's pain.

PMID- 7520558
TI  - [Hepatitis B and C markers in alcoholic liver diseases].
AB  - Hepatitis B and C virus contamination of 240 patients with alcoholic liver
      disease was studied. Hepatitis B virus core antibodies were present in 58
      alcoholic patients (24%) and hepatitis C virus antibodies in 30 alcoholic
      patients (12.5%). Both antibodies were present in 17 patients (7.1%). The
      prevalence of antibodies was more frequent in alcoholic female patients than in
      males. Data concerning the hepatitis B virus contamination in alcoholic liver
      patients with or without cirrhosis were similar. The frequency of hepatitis C
      virus antibodies in cirrhotic patients was more than in patients without
      cirrhosis. Female cirrhotic patients were more frequently C virus antibody
      positive than males. In female alcoholics the frequency of C virus antibodies was
      more in patients with cirrhosis than in the patients without cirrhosis. The viral
      serology and follow up of patients with alcoholic liver disease may be useful in
      detection of the early stage hepatocellular carcinoma.

PMID- 7520564
TI  - [Resistance to the organophosphate insecticides temephos and malathion in Culex
      pipiens L. (Diptera, Culicidae) from the Adriatic coast near Friuli].
AB  - Susceptibility to organophosphorus insecticides Temephos and Malathion was tested
      in Culex pipiens L. larvae from Friuli Adriatic coast (North-East of Italy). The
      samples were collected in various sites of three zones with different intensity
      of insecticidal treatments. Tests were made following the W.H.O. recommendations.
      The tests were made on larval samples which were exposed for 24 hours to
      ascending concentrations of each insecticide. From the observed percentage
      mortalities the LC50 and LC90 values were calculated. The resistance ratio was
      obtained comparing the CL50 values with reference CL50 values provided by the
      W.H.O. The obtained data suggest the existence of Cx. pipiens populations
      resistant to the tested chemicals in the most intensively treated touristic zone
      (Lignano Sabbiadoro). The samples collected in an agricultural zone with no
      mosquito control treatments showed a slight reduced susceptibility to the tested
      compounds.

PMID- 7520565
TI  - Antenatal glucocorticoid corrects pulmonary immaturity in experimentally induced
      congenital diaphragmatic hernia in rats.
AB  - Congenital diaphragmatic hernia, a highly lethal condition, displays at term the
      pulmonary biochemical and morphologic immaturity characteristic of premature
      delivery. We hypothesized that antenatal glucocorticoid, now the standard
      treatment to prevent hyaline membrane disease in premature human beings, might
      correct the parameters of the pulmonary biochemical and morphologic immaturity in
      severe congenital diaphragmatic hernia. A total of 112 fetal rats with or without
      nitrofen-induced congenital diaphragmatic hernias from 34 pregnancies were
      treated antenatally with either saline or dexamethasone. Antenatal dexamethasone
      increased the lung disaturated phosphatidylcholine content, reduced the lung
      glycogen concentration, reduced the saccular septal thickness, and increased the
      mean saccular size and volume fraction of saccules in the lungs of rats with
      large congenital diaphragmatic hernia in comparison with similar rats not so
      treated. All differences were statistically significant. Antenatal glucocorticoid
      therapy was efficacious in treating rats with nitrofen-induced congenital
      diaphragmatic hernia. This encouraging finding warrants further investigation in
      a large animal model with surgically created congenital diaphragmatic hernia.

PMID- 7520566
TI  - Correct in vivo RNA splicing of a mitochondrial intron in algal chloroplasts.
AB  - The self-splicing group II intron (rl1) from Scenedesmus obliquus mitochondria
      together with its 6 bp intron binding site (IBS1) were inserted in the correct
      and inverse orientation into the chloroplast tscA gene from C.reinhardtii.
      Precursor RNA derived from the chimeric tscA-rl1 gene can be used to demonstrate
      in vitro self-splicing of the rl1 intron RNA. Using the particle bombardment
      technique, the tscA-rl1 construct was transferred into the chloroplast of the
      unicellular alga Chlamydomonas reinhardtii. We recovered transformants which
      contain the chimeric tscA-rl1 gene as shown by Southern analysis. Hybridization
      and PCR analysis of transcripts confirmed that the heterologous intron is
      correctly spliced in vivo. From sequencing of cDNA clones we conclude that the
      IBS1 sequence is sufficient for correct splicing of the mitochondrial intron in
      C. reinhardtii chloroplasts. Using specific probes, we demonstrate by Northern
      hybridization that the mature RNA, as well as an intron-3' exon intermediate,
      accumulate in transformants containing the rl1 intron, correctly inserted into
      the tscA gene. As expected, no RNA splicing at all was observed when the intron
      had an inverted orientation within the tscA gene. In addition, a mutated intron
      RNA with an altered 3' terminal nucleotide was tested in vivo. In contrast to
      similar mutants examined in vitro, this mutated RNA shows accumulated intron and
      intron-3' exon intermediates, but no ligated exons at all. Our approach should
      prove useful for elucidating nucleotide residues involved in splicing of
      organelle introns in vivo.

PMID- 7520567
TI  - Monoclonal antibodies targeted to alpha-oligonucleotides. Characterisation and
      application in nucleic acid detection.
AB  - The aim of the present study was to test the antigenicity of alpha
      deoxyribonucleotides in order to develop a new tool for the detection of nucleic
      acid sequences for use in diagnostic applications. We describe four monoclonal
      antibodies (Mabs) which recognize alpha-deoxyribonucleotides. Two were raised
      against a poly(alpha-dT) sequence and specifically recognized the alpha-dT
      nucleotide. Two were raised against a sequence containing all four common
      nucleotides as alpha-nucleotides and, surprisingly, only recognized the alpha-dG
      nucleotide. For all four Mabs, no cross reactivity was observed with beta
      oligonucleotides. These Mabs were reactive with alpha-oligonucleotide sequences
      whether these sequences were single-stranded or hybridized to DNA or RNA. The
      four Mabs were tested in a sandwich hybridization assay that consisted of an
      alpha-oligonucleotide (for target sequence recognition), one of the four Mabs
      (for recognition of the hybridized alpha-oligonucleotide), and goat anti-mouse
      antibody conjugated to horse radish peroxidase (HRP) (for detection). One of the
      monoclonal antibodies, Mab 2E11D7, was directly conjugated to HRP and used in
      sandwich hybridization to detect PCR fragments of HPV 18 DNA. The sensitivity of
      this reaction was 1 pg of plasmid DNA containing the HPV 18 fragment. The
      specificity of the detection was demonstrated using HPV 6/11 and 16 DNA
      sequences.

PMID- 7520568
TI  - The human Y4 small cytoplasmic RNA gene is controlled by upstream elements and
      resides on chromosome 7 with all other hY scRNA genes.
AB  - Ro ribonucleoproteins (RNP) constitute a class of evolutionarily conserved small
      cytoplasmic (sc) RNPs whose functions are unknown. In human cells four
      distinctive scRNAs designated hY1, hY3, hY4 and hY5 are synthesized by RNA
      polymerase III (pol III) and accumulate as components of Ro scRNPs. The
      previously isolated hY1 and hY3 genes contain upstream sequences similar to the
      class III promoters for U6 and 7SK snRNAs. Additional mammalian Y scRNA genes
      have been refractory to cloning due to interference from numerous hY-homologous
      pseudogenes and studies of hY RNA genes have been sparse. Although homologs of
      hY1 and hY3 RNAs exist in rodent cells, the smaller Y4 and Y5 RNAs do not which
      has allowed us to localize the hY4 scRNA gene to human chromosome 7 by assaying
      for its transcript in rodent X human somatic cell hybrids (SCH). A chromosome 7
      enriched yeast artificial chromosome (YAC) library was then screened and the
      authentic hY4 sequence was isolated by strepavidin--biotin-mediated hybrid
      selection followed by poly(dA)-tailing and hemispecific PCR. The region upstream
      of the hY4 sequence contains a TATAAAA motif centered at -26, a candidate
      proximal sequence element at -63, and three octamer-like sequences located
      between -260 and -200. hY4 RNA is readily detectable on Northern blots after
      transient transfection of the hY4 gene into mouse cells but not after
      transfection of a construct in which the 5' flanking region was deleted. SCHs and
      chromosome 7-enriched YACs were used to demonstrate that all four hY RNA genes
      reside on human chromosome 7.

PMID- 7520569
TI  - Inappropriate transcription from the 5' end of the murine dihydrofolate reductase
      gene masks transcriptional regulation.
AB  - Using the nuclear run-on assay we found that in proliferating cells the
      transcription rate in the 5' end of the murine dihydrofolate reductase (dhfr)
      gene was approximately ten-fold higher than in the 3' end of the gene, suggesting
      transcriptional attenuation within the dhfr gene. However, when the transcription
      rate was measured by pulse-labeling, the rate was uniform throughout the gene,
      and the 5' dhfr signal was approximately ten-fold lower relative to a control
      gene signal than in the run-on assay. Previously, the activity of a dhfr promoter
      linked to a luciferase reporter gene was shown to increase about ten-fold at the
      G1/S-phase boundary following stimulation of serum-starved cells. To determine if
      the run-on procedure would detect growth regulation of the endogenous dhfr gene,
      serum-starved and -stimulated NIH 3T3 cells were analyzed. Using a dhfr 5' end
      probe no difference in transcription rate between these growth states was
      detected and the dhfr 3' end probe did not detect signal above background. In a
      cell line that was amplified at the dhfr locus, the transcription rate in the 5'
      end of the gene increased less than two-fold in stimulated cells, but the rate in
      the 3' end of the gene increased five- to seven-fold. Therefore, the dhfr gene is
      growth regulated at the level of transcription, but the nuclear run-on assay was
      only able to detect a difference in transcription rate in the 3' end of the gene
      in amplified cells. We suggest that isolation of nuclei may activate dhfr
      transcription complexes that normally are activated only at the G1/S-phase
      boundary.

PMID- 7520572
TI  - Expression of keratin 20 in malignant eccrine poromas.
AB  - Eight cases of malignant eccrine poromas were studied immunohistochemically with
      a broad panel of antibodies in order to better characterise the spectrum of their
      differentiating pathways. Special attention was paid to the expression of
      cytokeratins, mainly the newly recognised keratin 20. In general, the pattern of
      staining agreed to previous studies. Anyway, a non-expected positivity with
      keratin 20 was seen in two cases. The usefulness of the immunohistochemistry to
      discover areas with masked differentiation in adnexal tumours of the skin was
      once more confirmed.

PMID- 7520571
TI  - A simplified method for single-cell RT-PCR that can detect and distinguish
      genomic DNA and mRNA transcripts.

PMID- 7520573
TI  - Diffuse alveolar damage in the rat lung after short and long term exposure to
      nitrogen dioxide.
AB  - In order to quantify parenchymal, vascular and epithelial changes occurring in
      the exudative and organizing phase of diffuse alveolar damage (DAD) induced by
      inhaled NO2 groups of 7 rats were continuously exposed to 5, 10 or 20 ppm NO2 for
      3 and 25 days alternatively. AgNOR analysis revealed the highest proliferative
      activity in the epithelium of the respiratory bronchioles. In this region already
      after 3d exposure to 5 ppm the maximum AgNOR number was reached. In contrast to
      long-term exposure after 3d exposure to 5 and 10 ppm NO2 the AgNOR number in the
      respiratory bronchioles was significantly higher than in central airway
      epithelia. After long-term exposure to 5 and 10 ppm AgNOR number decreased to
      normal values or showed no further significant increase, long-term exposure to 20
      ppm resulted in a further increase of the AgNOR number. A significant increase of
      the alveolar circumference and decrease of alveolar surface density was found
      after an exposure to 20 ppm for 3d and long-term exposure to 10 and 20 ppm NO2,
      whereas the 5 ppm exposure groups disclosed no significant change of these
      values. Medial hypertrophy was detected after exposure to 10 and 20 ppm NO2 for
      25 days, after the exposure to 5 ppm for 3d and 25d medial thickness was
      significantly decreased due to vasodilation induced by NO, one of the major
      reaction products of NO2.

PMID- 7520575
TI  - Growth, morphology, and morphometry of human hypertrophic prostate cells treated
      with suramin in vitro.
AB  - This work studies the effects of suramin on the growth and morphology of cell
      strain U285, obtained from human prostate hypertrophic tissue and cultured in
      vitro. The FRAME cytotoxicity test was performed to evaluate the inhibition of
      growth induced by suramin. Cells were exposed to suramin at the time of seeding
      and 24 hours later; neutral red was added with and without suramin. An optical
      microscope connected to a computer-aided system and a scanning electron
      microscope were used to study morphological changes induced by suramin. Growth
      inhibition depends on drug concentration and exposure period. Moreover, the
      effect of suramin on neutral red uptake is reversible. Suramin 1,000 microM
      causes the cells to become spheroid, and they fail to form a monolayer. Our data
      indicate that the addition of suramin during the lag phase decreases the rate of
      cell proliferation.

PMID- 7520574
TI  - Proliferating cell nuclear antigen (PCNA) expression of megakaryocytopoiesis in
      normal human bone marrow and reactive lesions with special emphasis on HIV
      myelopathy.
AB  - A morphometric analysis was performed on bone marrow trephine biopsies using
      sequential double-immunostaining, to evaluate endoreduplicative activity of
      megakaryocytopoiesis. A total of 104 marrow specimens were studied with
      employment of monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen
      PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa). In addition to the
      control group patients included non-specific inflammatory changes, HIV-myelopathy
      with normal or decreased platelet counts, idiopathic thrombocytopenic purpura
      (ITP), and finally reactive thrombocytosis (TH). To exclude an undue
      overexpression of PCNA, in a comparative pilot study we also applied MIB1 (Ki-67
      antigen) on normal bone marrow specimens. In accordance with the various
      modalities of cell-cycle marker expression, no significantly different findings
      were disclosed. PCNA-labelling index was relatively low, ranging from 0.8 to 1.7%
      of the total megakaryocytopoiesis (promegakaryoblasts to mature platelet-shedding
      megakaryocytes). A significant relationship between megakaryocyte size and PCNA
      expression was determinable. This implies that some of the cases with a
      prevalence of small megakaryocytes, like ITP, have the tendency to show a higher
      proportion of positively-stained cells. Moreover, this feature confirms a
      hypothesis postulating a decrease in the time for DNA-synthesis (S-phase) and a
      relative prolongation of the G1/G2-phases of the cell-cycle at higher ploidy
      levels (large-sized megakaryocytes). On the other hand, it may be speculated that
      some of the hyperpolyploid giant megakaryocytes may have reached their endstage
      of endoreduplication and enter into G0-phase. In comparison with the control
      group and the other entities under study, a significant reduction of PCNA
      reactivity was recognizable in HIV-myelopathy accompanied by
      thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520570
TI  - PRP28, a 'DEAD-box' protein, is required for the first step of mRNA splicing in
      vitro.
AB  - We previously reported the isolation of PRP28, a gene in Saccharomyces cerevisiae
      whose activity is required for the first step of nuclear mRNA splicing in vivo.
      Sequence analysis revealed that PRP28 is included in the 'DEAD-box' gene family,
      members of which are thought to function as ATP-dependent RNA helicases. Genetic
      interactions led us to suggest that PRP28 is functionally associated with the
      U4/U5/U6 snRNP. We have now purified the PRP28 protein from S. cerevisiae and
      demonstrated that it is required for the first step of splicing in vitro.
      Interestingly, PRP28 is not a stably associated snRNP protein. Strand
      displacement assays indicate that PRP28 does not exhibit RNA helicase activity,
      suggesting that an additional factor or factors may be required for its
      activation.

PMID- 7520576
TI  - Elevated expression of estramustine binding protein (EMBP) in prostatic
      intraepithelial neoplasia (PIN) compared with malignant and benign prostatic
      epithelia.
AB  - The expression of estramustine-binding protein (EMBP) was studied
      immunohistochemically in whole-mount prostate sections. Specimens were taken from
      the prostates of 15 patients who had undergone total prostatectomy due to
      localized (TOd-T2 NO MO) prostatic cancer (PC). Almost all the examined whole
      mount sections displayed areas with prostatic intraepithelial neoplasia (PIN).
      PIN is regarded as the main precursor of invasive PC. High- and low-grade PIN
      expressed EMBP. The average positively stained areas accounted for averages of
      69.2% and 48.7%, respectively. High-grade PIN contained the highest EMBP levels
      of all the investigated (benign and malignant) epithelia, followed by moderately
      differentiated PC. With regard to areas with PC, the highest levels of EMBP
      expression (61.3%) were observed in moderately differentiated PC; poorly
      differentiated PC came second. Of all the examined epithelia, EMBP levels were
      lowest in well-differentiated PC (25.8%). Normal prostatic epithelia and
      hyperplasia were characterized by low EMBP expression, although somewhat higher
      than well-differentiated PC. A moderate expression (45%) was observed in the
      seminal vesicles. According to these results, EMBP was expressed mainly in the
      diseased peripheral zone (PZ), where PIN and prostatic cancer have their highest
      prevalence.

PMID- 7520577
TI  - Detection of prostate cancer in males with prostatism.
AB  - The present study was designed to compare the prostate cancer detection rate,
      sensitivity, specificity, and positive predictive value of digital rectal
      examination (DRE) and serum prostatic specific antigen (PSA) in a consecutive
      cohort of males presenting to a single institution with clinically significant
      prostatism. The study population was comprised of 224 consecutive males with
      clinically significant prostatism referred to the Prostate Center at the Medical
      College of Wisconsin between June 1990 and December 1991. Subjects were
      considered to have clinically significant prostatism if they elected to pursue
      medical or surgical therapy following exclusion of carcinoma of the prostate. The
      initial examination consisted of a Boyarsky symptom score assessment, DRE,
      uroflowmetry, postvoid residual determination, serum PSA level, and transrectal
      prostatic ultrasonography. Subjects with an abnormality on DRE or serum PSA > 4
      ng/dl were advised to undergo transrectal prostatic biopsy. Of the 224 subjects,
      40 (17.9%) had an abnormal DRE and 57 (25.4%) had an elevated serum PSA > 4
      ng/dl. The overall detection rate of prostate cancer in the study population was
      6.7%. The prostate cancer detection rates for PSA alone and DRE alone were 5.8%
      and 5.3%, respectively. The sensitivity, specificity, and positive predictive
      values of PSA alone were 86.7%, 80.9%, and 25.0% and of DRE alone 80.0%, 86.3%,
      and 30.0%, respectively. Receiver operator characteristic (ROC) curves were
      constructed for the entire study population in order to compare the screening
      measures serum PSA and PSA density. The area under the curves was 0.88 for both
      tests, indicating that these screening tests for prostate cancer were not
      significantly different. The present study demonstrated that males with
      clinically significant prostatism represent a high risk cohort for detecting
      prostate cancer. DRE and PSA are equally effective measures for detecting
      prostate cancer. PSA density does not offer any advantage over serum PSA in
      screening for prostate cancer, except in the subset of patients with a normal DRE
      and serum PSA levels between 4.0 and 9.9 ng/dl.

PMID- 7520578
TI  - Histological evaluation of benign prostatic hyperplasia treated by long-term
      administration of chlormadinone acetate (CMA).
AB  - Although the clinical effects of attempted nonsurgical treatment of benign
      prostatic hyperplasia have been well documented, detailed histological evaluation
      of the effects of treatment appears to be limited. The effect of long-term
      administration of an antiandrogen, chlormadinone acetate (CMA), on benign
      prostatic hyperplasia was evaluated with histological comparison of two biopsy
      specimens, one before treatment and one after treatment. Secretory epithelium
      showed obvious regressive changes with occasional basal cell prominence after CMA
      treatment. Stromal elements, however, did not show any marked changes, except for
      occasional edematous loosening. Scores of multiple epithelial parameters tended
      to be correlated with clinical improvement in urinary obstructive symptoms,
      especially in patients with predominant glandular hyperplasia. These results
      suggest that long-term administration of the potent antiandrogen CMA to inhibit
      dihydrotestosterone-receptor binding might be a useful therapeutic maneuver in
      patients with glandular hyperplasia, without any deterioration of the stromal
      component.

PMID- 7520579
TI  - PR92 antigen in human prostate fluid: elevated levels in prostate cancer.
AB  - In this preliminary study, we report that an enzyme-linked immunofluorescence
      assay (EFLA) was developed for the determination of PR92 antigen in prostatic
      fluid, utilizing anti-PR92 monoclonal antibody. Fluid samples from 64 patients
      were assayed. PR92 antigen was expressed as unit per microgram (U/microgram) of
      prostatic fluid proteins. One hundred percent of men (7 out of 7) less than 50
      years of age demonstrated concentrations less than 25 U/micrograms; 91% of men
      (10 out of 11) with documented carcinoma, and only 9.5% of men (2 out of 21) with
      benign prostatic hyperplasia, demonstrated concentrations above 230 U/micrograms.
      The mean concentration of PR92 antigen in prostatic fluid of a group of patients
      suspected of having prostate cancer (high-risk group; 227 +/- 42 U/micrograms)
      was significantly greater than that of those with benign prostatic hyperplasia
      (87 +/- 23 U/micrograms; P = 0.05). Further evaluation of this potential marker
      and of other antigens within the prostatic fluid is warranted.

PMID- 7520580
TI  - Bioenergetic theory of prostate malignancy.
AB  - Normal and benign prostate hyperplasia (BPH) prostate is characterized by the
      presence of extraordinarily high levels of citrate. Presumably, this results from
      the inability of the prostate epithelial cells to oxidize citrate due to a
      limiting mitochondrial (m-) aconitase. In contrast, prostate carcinoma (CA) is
      not characterized by high citrate levels. Malignant prostate epithelial cells
      apparently undergo a metabolic transformation from citrate-producing to citrate
      oxidizing cells. A consequence of citrate production in normal and BPH cells is
      an inefficient and low level of ATP production. It is proposed that the process
      of malignancy necessitates an energy production that cannot be provided by
      citrate-producing cells. Consequently, the transformation of prostate epithelial
      cells to citrate-oxidizing cells which increases the energy production capability
      is essential to the process of malignancy and metastasis. The metabolic
      transformation likely occurs as a premalignant or early malignant stage. This
      bioenergetic theory of prostate malignancy, if correct, will provide new
      approaches to the diagnosis and treatment of CA.

PMID- 7520581
TI  - Epithelioid sarcoma in childhood: An immunohistochemical, electron microscopic,
      and clinicopathologic study of 11 cases under 15 years of age and review of the
      literature.
AB  - Epithelioid sarcoma in a rare tumor and most of the cases occur in young adults.
      It is rare in childhood. We have been able to obtain data and histologic material
      for 11 patients with this disease. The primary sites were head and neck in three
      patients, inguinal region in one, and extremities in seven. The age range of the
      patients was 12 weeks to 13 years. There was a preponderance of males over
      females with a ratio of 1.75. The tumors presented with a typical nodular
      necrotizing pattern. In three cases giant osteoclast-like cells were present. The
      immunohistochemistry and electron microscopy showed features consistent with
      previous observations on epithelioid sarcomas. In one case islands of small dark
      cells noted on light microscopy were surrounded by basal lamina on electron
      microscopy. The cells inside the nests were undifferentiated. Six tumors studied
      by flow cytometry were in DNA diploid range. On follow-up, five children are
      alive and well 2 to 7 years after treatment. Three children died of tumor
      progression with metastases to lymph nodes and lungs. One child had been
      diagnosed only recently, and in one the disease has run a protractive course with
      multiple recurrences. The behavior of these epithelioid sarcomas in children is
      similar to that seen in adults, the prognosis being dependent on radical tumor
      surgery preventing recurrent disease. Long-term follow-up is necessary because
      the tumor may recur many years after the primary tumor was removed.

PMID- 7520583
TI  - Simpson-Golabi-Behmel syndrome: disproportionate fetal overgrowth and elevated
      maternal serum alpha-fetoprotein.
AB  - Simpson-Golabi-Behmel (SGB) syndrome is an X-linked condition with pre- and
      postnatal overgrowth, characteristic facies, and visceral and skeletal anomalies.
      We report an affected male who presented at 16 weeks' gestation with elevated
      maternal serum alpha-fetoprotein (MSAFP). Fetal measurements at 20 and 31 weeks'
      gestation were disproportionate, with marked macrosomia but a low head to
      abdominal circumference ratio and normal femur length. Fetal overgrowth with
      elevated MSAFP may prove to be useful markers for the prenatal diagnosis of SGB
      syndrome.

PMID- 7520582
TI  - Analysis of delta F508 mutation in cystic fibrosis pathology specimens.
AB  - Incidence of delta F508, a severe mutation of the CFTR gene is found to be 36.3%
      in paraffin block cystic fibrosis liver tissues. Samples are histologically
      grouped according to severity of pancreatic involvement. Two families where delta
      F508 was detected postmortem and who have no living children, will have the
      chance for a prenatal diagnosis in the future pregnancies.

PMID- 7520584
TI  - Endothelial nitric oxide synthase in the human placenta: regional distribution
      and proposed regulatory role at the feto-maternal interface.
AB  - Feto-placental vessels lack innervation, hence control of this circulation is
      dependent on locally produced and circulating vasoactive factors. Functional
      studies have presented evidence that nitric oxide, a potent vasodilator and
      platelet anti-aggregating agent, may be generated into the feto-placental
      circulation, contributing to control of vascular tone. In view of the absence of
      nerves supplying the placenta the source of NO is likely to be endothelial. We
      have therefore investigated the localization of endothelial constitutive nitric
      oxide synthase (ecNOS) in human normal full-term placentae, using
      immunocytochemistry, with rabbit antiserum to a synthetic peptide, corresponding
      to amino acid residues 1172-1186 of human and bovine ecNOS. On Western blots of
      partially purified NO synthase extracted from placenta, the peptide antiserum
      reacted exclusively with a single protein band of approximately 135kDA.
      Immunoreactivity in tissue sections was localized to endothelium of umbilical
      artery and vein, and appeared uniform in sections at different levels along the
      cord. Staining in chorionic vessels was much more variable; it was present mainly
      in the larger vessels close to the cord where it had a patchy distribution.
      Staining was not seen in the endothelium of small feto-placental vessels. Strong
      immunoreactivity was evident in the syncytiotrophoblast of the placenta, although
      the intensity of staining was variable, being weaker along stem villi and
      strongest along terminal villi. The differential distribution and intensity of
      nitric oxide synthase immunoreactivity in the human placenta might indicate that
      locally produced, and in particular trophoblast-derived nitric oxide may play a
      pivotal role both in control of feto-placental vascular tone and as a platelet
      anti-aggregating agent in the utero-placental circulation.

PMID- 7520585
TI  - Quantitation of prostate-specific acid phosphatase in prostate cancer:
      reproducibility and correlation with subjective grade.
AB  - In this study, we quantitatively evaluated the intensity and extent of prostate
      specific acid phosphatase in immunocytochemically stained prostate carcinoma
      tissue sections by using a dual-wave-length-based image processing technique.
      Tissue sections were doubly stained in a standard way, i.e., prostate-specific
      acid phosphatase was immunocytochemically labeled by peroxidase-antiperoxidase
      (PAP) technique using diaminobenezidene (DAB) as the substrate and hematoxylin as
      a nuclear counterstain. Statistical analysis in this study indicated that the
      quantitative measures of the prostate-specific acid phosphatase staining (PAP
      DAB) are reproducible. We found that the quantitative intensity was generally
      proportional to the subjective intensity (graded as 1 to 4+) of PAP-DAB. Although
      the quantitative extent measurements compared with the subjective estimates of
      the percentage of tumor showing staining with PAP-DAB had a similar tendency,
      there were significant overlaps between extent of tumor staining falling in the
      mid-ranges. Because subjective grading of immunocytochemical prostate-specific
      acid phosphatase has been thought to be a useful marker of tumor differentiation
      in patients with prostate carcinoma, we also evaluated the relationship of the
      quantitative measures of PAP-DAB staining to other predictors of patient outcome,
      including histologic grades (Gleason score and MD Anderson grading scheme) and
      clinical stage. We confirmed that quantitative intensity and extent of PAP-DAB
      staining were independent of histologic grades and stage, just as the subjective
      measures of intensity and extent were found to be. Possible explanations of this
      lack of correlation are discussed.

PMID- 7520587
TI  - Prostate-specific antigen screening for prostate cancer: no reduction in Gleason
      scores.
AB  - Skepticism regarding prostate-specific antigen (PSA) screening arises from the
      possibility that screening procedures increase the yield of diagnosed prostate
      cancers occurring in an indolent form that does not require treatment. If PSA
      screening serves only to increase the yield of clinically trivial prostate
      cancer, one would expect a drop in the average Gleason score of prostate cancers
      detected with PSA screening compared with prostate cancers detected before the
      advent of PSA screening. In a 3-yr study of newly diagnosed prostate cancer,
      there was almost a 7-fold increase in PSA screening tests ordered between 1989
      and 1992 and a greater than 2-fold increase in the number of newly diagnosed
      prostate cancers. In the same time period, the average Gleason scores of newly
      diagnosed prostate cancer increased slightly (from 6.2 to 6.5). In this study
      there was no prognostic difference (as predicted by Gleason score) between
      prostate cancers in populations whose cancers were diagnosed before and after the
      increased use of PSA as a screening tool.

PMID- 7520588
TI  - [The overhead projector as an instrument in education].

PMID- 7520586
TI  - Immunohistochemical detection of Epstein-Barr virus-encoded latent membrane
      protein in Reed-Sternberg cells and variants of Hodgkin's disease.
AB  - A total of 186 specimens of Hodgkin's disease of various histologic types (127
      nodular sclerosis, 39 mixed cellularity, 14 lymphocyte predominance, 3 lymphocyte
      depleted, and 3 unclassified) were evaluated for the presence of latent membrane
      protein (LMP) and Epstein-Barr virus nuclear antigen-2, two Epstein-Barr virus
      encoded gene products that appear to play important roles in cell transformation
      and oncogenesis. Immunoreactivity for LMP was observed in Reed-Sternberg cells
      and variants of 27/39 (69%) cases of mixed cellularity type, 18/127 (14%) of
      nodular sclerosis type, 2/3 cases of lymphocyte depleted type, and 1/3 cases of
      unclassified type. All cases of lymphocyte predominance Hodgkin's disease were
      nonreactive for LMP. In cases that were reactive for LMP, staining was restricted
      to Reed-Sternberg cells and variants. Other cells within the proliferation, e.g.,
      lymphocytes, histiocytes, eosinophils, fibroblasts, etc., were nonreactive. The
      pattern of immunoreactivity for LMP was characterized by strong diffuse
      cytoplasmic staining, occasionally with membrane accentuation and/or paranuclear
      staining. Reactivity for LMP was demonstrated in cryostat sections and was also
      well preserved in paraffin sections of B5- or formalin-fixed tissues. Five of six
      specimens of Hodgkin's disease (4 mixed cellularity and 2 nodular sclerosis type)
      that occurred in HIV-positive patients exhibited immunoreactivity for LMP in Reed
      Sternberg cells and variants. Cryostat section studies for Epstein-Barr virus
      nuclear antigen-2 using monoclonal antibody PE-2 failed to reveal staining for 43
      cases (26 nodular sclerosis, 12 mixed cellularity, and 5 lymphocyte predominance)
      after a 2-h incubation with primary antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520589
TI  - Characterization and expression of two cDNAs encoding carbonic anhydrase in
      Arabidopsis thaliana.
AB  - Two distinct cDNA clones encoding carbonic anhydrase (CA) were isolated from an
      Arabidopsis thaliana lambda YES library. One of these clones, CA1, encodes a 36.1
      kD polypeptide and is essentially the same as a previously reported Arabidopsis
      CA cDNA (C.A. Raines, P.R. Horsnell, C. Holder, J.C. Lloyd [1992] Plant Mol Biol
      20: 1143-1148). Comparison of the derived amino acid sequence from this clone
      with other plant CAs suggests the presence of a chloroplastic transit peptide,
      which, when cleaved, would render a mature protein of 24.3 kD. The other
      identified clone, CA2, encodes a 28.3-kD polypeptide, which in addition to other
      residue changes, is 78 amino acids shorter at the N terminus than the primary
      product of CA1. The two cDNAs exhibit 76.9% sequence similarity at the DNA level
      and 84.6% identity between the predicted amino acid sequences. A polyclonal
      antibody generated against pea CA (N. Majeau, J.R. Coleman [1991] Plant Physiol
      100: 1077-1078) hybridized to two protein bands (25 and 28 kD) from a total leaf
      extract and to only one band (25 kD) from a chloroplastic protein extract. The
      data suggest that the CA2 protein is an extrachloroplastic form of CA, presumably
      localized in the cytoplasm. Southern analysis indicated that CA1 and CA2 are
      encoded by different genes. Northern analysis of total leaf RNA resulted in
      hybridization of CA1- and CA2-derived probes to two transcripts of 1.47 and 1.2
      kb, respectively. These data provide additional evidence that the CA2 clone is a
      full-length cDNA and that two transcribed CA genes are present in the Arabidopsis
      genome. Transcript levels of CA1 and CA2 decreased 70 and 20%, respectively, when
      mature plants were transferred to dark for 24 h. Seedlings germinated in the dark
      showed CA1 and CA2 transcript abundance levels of 4 and 22%, respectively, when
      compared with light-germinated seedlings. These data suggest that expression of
      CA1 is light regulated and dependent of leaf and/or chloroplast development. A
      possible role for cytoplasmic CA in the plant cell is discussed.

PMID- 7520590
TI  - Voltage gating of ion channels.

PMID- 7520591
TI  - Failure to inform of AFP test: birth defects--$4.3 million damages. Case in
      point: Basten by and through Basten v. U.S. 848 F. Supp. 2d 962 AL (1994).

PMID- 7520592
TI  - Economically important organic acid and enzyme products.

PMID- 7520593
TI  - Hepatotoxicity in irradiated nephroblastoma patients.

PMID- 7520595
TI  - Activation of T cells to peptides that span the 19 kDa protein of Mycobacterium
      tuberculosis.
AB  - It has been suggested that the cellular immune response to mycobacterial
      antigens, is implicated in the pathogenicity of inflammatory joint diseases such
      as rheumatoid arthritis. Therefore, the aim of this study was to identify T-cell
      epitopes in a series of 20-mer peptides spanning the entire 19-kDa protein of M.
      tuberculosis. Mononuclear cells obtained from six rheumatoid arthritis (RA)
      patients, were analyzed for their proliferation to both the 19-kDa containing
      immunoblot fraction and to the synthetic peptides. Mononuclear cells from three
      rheumatoid arthritis patients responded in a dose-dependent manner to peptides 1
      20, 60-79, 71-90, 82-101, 90-109 and 121-140, whereas the other eight peptides:
      11-30, 21-40, 41-60, 50-69, 100-119, 112-131, 131-150 and 140-159 did not
      stimulate significant proliferative responses in any of the patients tested.
      These results indicate, for the first time, the presence of dominant epitopes in
      the cellular immune response to the 19-kDa M. tuberculosis antigen by rheumatoid
      T cells.

PMID- 7520594
TI  - [Percutaneous treatment of hilar cholangiocarcinoma completed by high-dose rate
      brachytherapy. Experience in the first 5 cases].
AB  - Cholangiocarcinoma at the confluence of the hepatic ducts (Klatskin tumor) is a
      slowly growing malignancy with early onset of symptoms and poor outcome since
      surgery allows radical resection in only a minority of cases. Percutaneously
      placed biliary stents offer a good palliation, but tend to obstruct after 6-8
      months; then, retreatment requires exchange of the endoprosthesis or
      establishment of a permanent external-internal biliary drainage which offers, in
      some patients, a relatively long survival. Percutaneous intraluminal HDR
      brachytherapy might be a valid alternative as a definitive therapy or as a method
      to keep metallic stents patent for a long time. Five patients with hilar
      cholangiocarcinoma, diagnosed by means of ultrasound, Computed Tomography,
      percutaneous transhepatic cholangiography and transluminal biopsy, underwent
      double percutaneous external-internal biliary drainage. Dummy sources were
      introduced into the drainage catheters to allow dose distribution planning. The
      stepwise progression of the miniaturized high activity Iridium source inside the
      applicators, introduced into the drainage catheters, was controlled and monitored
      by a computer equipped with dedicated software. In the radiotherapy bunker, using
      the remote loading technique, percutaneous intracavitary high dose rate
      brachytherapy was delivered at the rate of 750 cGy per fraction, prescribed at 1
      cm from the center of the catheter, once a week, for 4 weeks. Nevertheless, only
      4 of 5 patients underwent the complete treatment. In one case, radiation
      treatment was discontinued after the first session because of digestive bleeding
      from a duodenal ulcer, supposingly as a consequence of the decubitus of a
      catheter tip. CT demonstrated rapid progression of the disease with neoplastic
      spread to the omentum and gallbladder wall thickening; a gallbladder malignancy
      was then suspected and the patient was no more eligibile for brachytherapy.
      Subsequently, Carey-Coons endoprostheses were inserted to prevent post-actinic
      strictures and removed after three months. After completing radiation therapy,
      control cholangiograms demonstrated in all cases improvement of neoplastic
      strictures. The first two patients we treated show no signs of tumor recurrence
      at 4 and 1 months, respectively, after endoscopic removal of the stents. The
      third patient is still bearing 2 Carey-Coons endoprostheses to be removed after 3
      months. The last patient with supposingly partial success of bracytherapy, was
      treated with two Strecker nitinol stents.

PMID- 7520597
TI  - [Proper use of prostate specific antigen].
AB  - Prostate specific antigen (PSA) has become the best marker for prostatic
      carcinoma. PSA is secreted by the glandular cells of prostatic epithelium and is
      specific for any normal, hyperplasic and tumoral prostatic tissue. PSA is
      excreted in blood that render its dosage accessible for clinical purpose. Two
      different tests are now used: Tandem test R is a radioimmunological test (N1:0-4
      ng/mL), and Pros check test uses an immunoenzymatic method and is considered to
      be more sensitive (N1: < 2.5 ng/mL). PSA increases of 35 ng/mL for every other
      gram of hyperplastic prostatic tissue and of 3.5 ng/mL by gram of prostatic
      cancer. This test allows detection of prostate carcinoma with a positive
      predictive value of 49% when PSA > 4 ng/mL and 75% when PSA > 10 ng/mL. However,
      only biopsies will confirm the diagnostic of prostate cancer. For the patients
      with an increased PSA and no cancer founded by random biopsies, an increase of
      PSA level in the next year suggests prostate carcinoma. When the diagnostic of
      prostate cancer has been made, a PSA < 15 ng/mL suggests a low stage carcinoma
      (B1 or B2). When PSA > 75 ng/mL, there is a high probability that this cancer is
      node positive. Between this values, PSA cannot make the difference between stage
      B, C or D. The more sensitive test (Pros check) must give undetectable level
      after radical prostatectomy. For high stage lesion treated by hormonotherapy, or
      chemotherapy or radiation therapy, PSA is a good indicator of response to therapy
      and recurrence after therapy.

PMID- 7520596
TI  - [Surgical treatment of prostate cancer].
AB  - Surgical treatment of prostatic carcinoma is used at the two extremities of the
      course of the disease. In the initial stage when the tumour is confined to the
      prostate, radical prostatectomy entails the best prognosis for cure by removal of
      the tumour, at the cost of slight morbidity, particularly the risk of subsequent
      impotence. However, the volume of the tumour often is greatly underestimated and
      the surgical excision does not reach healthy tissue in almost one out of two
      cases; in this case, it cannot be considered fully curative. Surgery has an
      important role in the metastatic phase, either as hormonal treatment (surgical
      castration) or with the aim of re-establishing urine flux (transurethral
      prostatic resection or urine derivation).

PMID- 7520598
TI  - Prostate cancer screening.

PMID- 7520599
TI  - Prostate cancer screening.

PMID- 7520600
TI  - Prostate cancer screening.

PMID- 7520602
TI  - Co-opting a blind watchmaker.

PMID- 7520601
TI  - Gap junctions and intercellular communications.

PMID- 7520603
TI  - Delocalization of Vg1 mRNA from the vegetal cortex in Xenopus oocytes after
      destruction of Xlsirt RNA.
AB  - The Xlsirts are a family of transcribed repeat sequence genes that do not code
      for protein. Xlsirt RNAs become localized to the vegetal cortex of Xenopus
      oocytes early in oogenesis, before the localization of the messenger RNA Vg1,
      which encodes a transforming growth factor-beta-like molecule involved in
      mesoderm formation, and coincident with the localization of Xcat2 transcripts,
      which encode a nanos-like molecule. Destruction of the localized Xlsirts by
      injection of antisense oligodeoxynucleotides into stage 4 oocytes resulted in the
      release of Vg1 transcripts but not Xcat2 transcripts from the vegetal cortex.
      Xlsirt RNAs, which may be a structural component of the vegetal cortex, are a
      crucial part of a genetic pathway necessary for the proper localization of Vg1
      that leads to subsequent normal pattern formation.

PMID- 7520604
TI  - Treatment of murine lupus with CTLA4Ig.
AB  - The interaction of B7-related molecules on antigen-presenting cells with CD28 or
      CTLA-4 antigens on T cells provides a second signal for T cell activation.
      Selection inhibition of the B7-CD28 or B7-CTLA-4 interactions produces antigen
      specific T cell unresponsiveness in vitro and suppresses immune function in vivo.
      To determine whether selective inhibition of the B7-CD28 or B7-CTLA-4
      interactions could suppress spontaneous autoimmune disease, a B7-binding protein
      was generated by genetic fusion of the extracellular domain of murine CTLA-4 to
      the Fc portion of a mouse immunoglobulin G2a monoclonal antibody (muCTLA4Ig). In
      lupus-prone NZB/NZW filial generation (F1) mice, treatment with muCTLA4Ig blocked
      autoantibody production and prolonged life, even when treatment was delayed until
      the most advanced stage of clinical illness. These findings suggest a possible
      role for human CTLA4Ig in the treatment of autoimmune diseases in humans.

PMID- 7520606
TI  - Pseudomonas cepacia in cystic fibrosis.

PMID- 7520605
TI  - Regulatory T cell clones induced by oral tolerance: suppression of autoimmune
      encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune
      disease that serves as an animal model for multiple sclerosis. Oral
      administration of myelin basic protein (MBP) suppresses EAE by inducing
      peripheral tolerance. T cell clones were isolated from the mesenteric lymph nodes
      of SJL mice that had been orally tolerized to MBP. These clones were CD4+ and
      were structurally identical to T helper cell type 1 (TH1) encephalitogenic CD4+
      clones in T cell receptor usage, major histocompatibility complex restriction,
      and epitope recognition. However, they produced transforming growth factor-beta
      with various amounts of interleukin-4 and interleukin-10 and suppressed EAE
      induced with either MBP or proteolipid protein. Thus, mucosally derived TH2-like
      clones induced by oral antigen can actively regulate immune responses in vivo and
      may represent a different subset of T cells.

PMID- 7520608
TI  - Involvement of clonal deletion in immunotolerance induction: tests of Tacrolimus
      administration in rat renal transplantation.

PMID- 7520607
TI  - Transient iron overload with bleomycin detectable iron in the plasma of patients
      with adult respiratory distress syndrome.
AB  - BACKGROUND: A retrospective study was conducted to evaluate iron status in plasma
      samples collected from five patients with the adult respiratory distress syndrome
      (ARDS) who had bleomycin detectable iron in at least one sample. Ten patients
      with ARDS with no evidence of bleomycin detectable iron and 10 healthy
      individuals served as controls. METHODS: Evidence of iron overload was
      established by measuring the percentage saturation of plasma transferrin. In each
      case the bleomycin assay for redox active, chelatable iron was used to measure
      plasma levels of non-transferrin bound iron in the low micromolar range; assays
      for total plasma iron and transferrin were performed to establish a diagnosis of
      transient iron overload. The effect of this on the ability of transferrin to act
      as a plasma antioxidant was assessed using two different assay systems. RESULTS:
      The five patients with evidence of transient iron overload (mortality 4/5)
      represented 33% of the total population of patients with ARDS (mortality 5/10)
      managed by the unit during the study period. All had low molecular mass iron
      detectable in their plasma and had clinical and biochemical evidence of
      multiorgan system failure as well as liver impairment. Compared with the ARDS and
      normal control populations, transferrin and albumin levels were low and the
      former failed to act as a plasma antioxidant in preventing free radical mediated
      damage to detector molecules. CONCLUSIONS: Patients with ARDS are thought to be
      under severe oxidative stress from their disease and from treatment with high
      inspired oxygen concentrations. A subgroup of patients with ARDS has been
      identified who displayed evidence of transient iron overload as a result of which
      their plasma iron binding antioxidant protection was greatly compromised. This
      finding must be considered a serious additional risk factor for oxidative stress.

PMID- 7520609
TI  - Soluble e-selectin, ICAM-1, and VCAM-1 levels in renal allograft recipients.

PMID- 7520610
TI  - Study of the effect of immunosuppressive agents on renal cytochrome P-450 system
      in the rat.

PMID- 7520611
TI  - Clinical experience of FK 506 for renal allograft transplantation.

PMID- 7520614
TI  - Morphopathological findings of renal allografts under FK 506 therapy. Japanese FK
      506 Study Group.

PMID- 7520613
TI  - Immunosuppressive mechanisms of deoxymethylspergualin and FK 506 on in vitro
      cytotoxic T lymphocytes.

PMID- 7520612
TI  - FK 506 used as rescue therapy for refractory liver allograft rejection.

PMID- 7520615
TI  - Induction of tolerance by intrathymic injection of donor bone marrow cells in the
      rat: simultaneous heart and skin allograft model.

PMID- 7520616
TI  - Organ-specific tolerance induced by intrathymic injection of donor bone marrow
      cells and FK 506 or antilymphocyte serum in rat heart transplantation.

PMID- 7520617
TI  - Use of cytokines for efficient introduction of foreign genes into the
      hematopoietic stem cell.

PMID- 7520618
TI  - Analysis of serum ferritin changes after kidney transplantation: a prospective
      study of 123 cases.

PMID- 7520619
TI  - Clinical implications of the presence of hepatitis C virus antibodies after
      kidney transplantation: results of a study using second-generation assays for
      anti-HCV.

PMID- 7520621
TI  - Hepatitis B and C in renal transplantation in Taiwan.

PMID- 7520620
TI  - Effects of a new solution for cold kidney preservation studied on isolated
      perfused rat kidney.

PMID- 7520622
TI  - Living donor kidney transplantation in Japan.

PMID- 7520623
TI  - Monitoring of FK 506 blood levels in kidney transplant recipients.

PMID- 7520624
TI  - Prevalence and clinical significance of hepatitis C in kidney transplantation.

PMID- 7520625
TI  - Current status of viral hepatitis and HIV transmission in renal transplant
      recipients: a study in Southeast Asia.

PMID- 7520626
TI  - Expression of tumor necrosis factor and tissue adhesion molecules in the failed
      renal allograft.

PMID- 7520627
TI  - Intensive care after orthotopic liver transplantation.

PMID- 7520628
TI  - Effectiveness of triple regimen immunosuppression in canine pancreatic
      allotransplantation.

PMID- 7520629
TI  - Successful swine small bowel transplantation using FK506: effect on endotoxin
      translocation.

PMID- 7520630
TI  - Adverse effect of rhG-CSF in the process of rat heart allograft rejection.

PMID- 7520631
TI  - FK 506 and deoxyspergualin: additive immunosuppressive effect on rat cardiac
      allograft rejection in vivo and mitogen-stimulated human lymphocyte responses in
      vitro.

PMID- 7520633
TI  - Effect of brequinar sodium on accelerated cardiac allograft rejection in
      presensitized recipients.

PMID- 7520635
TI  - Ameliorative effect of FK 506 on cold ischemia reperfusion injury of the rat
      liver.

PMID- 7520632
TI  - Heterotopic rat heart transplantation to the iliac vessels.

PMID- 7520636
TI  - FK 506 prevents critical warm ischemia damage to the pig liver and improves
      hepatic microcirculation.

PMID- 7520634
TI  - Problems of bone marrow transplantation in Japan.

PMID- 7520638
TI  - Comparison of patterns of rejection in multivisceral transplantation and
      abdominal organ cluster transplantation in pigs.

PMID- 7520637
TI  - Protective effect of adult T cell leukemia-derived factor on reperfusion injury
      in multivisceral transplantation.

PMID- 7520639
TI  - [A cytofluorescence study of the peripheral blood in radiation exposure].
AB  - The cytofluorescent probing method has shown that the radiation action under
      sharp irradiation regime in experimental animals and chronic regime in people
      influences the level of synthetic processes in lymphocytes and granulocytes of
      peripheral blood, characterized by alpha-index (RNA/DNA). The correlation has
      been found between alpha-index, survivability, doses. alpha-Index can be used to
      estimate the radiation biological effects and radiosensitivity testing.

PMID- 7520640
TI  - [The dynamics of the structural-functional parameters of the chromatin in
      regenerating rat liver].
AB  - Three fractions of chromatin were obtained from nuclei of the regenerating rat
      liver: transcriptionally low active (TLA), transcriptionally active (TA) and
      membrane-bound (MB). Changes in fractions distribution, functional activities and
      structural reorganization during the cell cycle were found. At the peak of
      transcription (15 h after PHE) an increase in the relative content of TA and MB
      fractions as well as an increase of the level of incorporated labelled precursors
      in RNA of TLA and TA fractions compared to control were observed. At the peak of
      replication (20 h after PHE) the relative content of TA and MB fractions
      increased as well, while the level of incorporation of labelled precursors in RNA
      of TLA and TA fractions was significantly lower than in control.

PMID- 7520641
TI  - Angiogenic process in bacillary angiomatosis.
AB  - Eight cases of cutaneous bacillary angiomatosis related to acquired
      immunodeficiency syndrome were studied by light and electron microscopy and by
      immunohistochemistry with a panel of antibodies specific for endothelial and
      histiocytic markers. Light microscopy showed an inflammatory reaction with florid
      neovascularization and clusters of Warthin-Starry-positive bacilli. In addition,
      solid areas of spindle cells were also present that in some cases mimicked
      Kaposi's sarcoma or other sarcomas. The investigation focused primarily on the
      spindle cell areas and the angiogenic process present in bacillary angiomatosis.
      By immunohistochemistry the lesions, including the spindle cell areas, expressed
      all endothelial markers used; CD34, factor VIII-related antigen, and Ulex
      europaeus 1 were the most consistent in intensity, however. In those areas the
      other endothelial markers, BNH9 and Psophocarpus tetragonolobus, were weak and
      not always uniform. The macrophage/monocyte markers used were alpha 1
      antitrypsin, lysosome, kp1 (CD68), and polyclonal factor XIIIa; these revealed a
      sprinkle of positive cells ranging from 10% to 20% of the cell population. By
      electron microscopy primitive capillaries were present lined by plump endothelial
      cells containing frequent abluminal microprocesses forming intercellular lumina.
      Mitoses and intracytoplasmic lumen formation were infrequent. The study
      illustrates that bacillary angiomatosis is composed of active endothelial
      neoformation with the spindle cells representing immature endothelial cells.
      Furthermore, the features of this angiogenic process recapitulate the morphologic
      events described in experimental models.

PMID- 7520644
TI  - [Symptomatic treatment of amyotrophic lateral sclerosis].
AB  - During a twelve year period 58 patients with motor neurone disease were admitted
      to the Department of Neurology, Odense University Hospital. The medical records
      were reviewed and different aspects of symptomatic treatment for these patients
      were recorded retrospectively. After the first admission 55% of the patients
      received out-patient treatment, while 31% had no further contact to the
      Department of Neurology. Forty-nine patients developed bulbar symptoms. Of these
      patients 41% were referred to a laryngologist, 27% were referred to a speech
      therapist and 10% to a nutritionist. Seven patients had a gastrostomy, while
      feeding tube was used by at least six patients. At the time of follow up 49
      patients had died, 63% in hospital. At least 22 patients were treated with
      morphine in the last period of their lives. In order to improve the symptomatic
      treatment in motor neurone disease we suggest that these patients are treated at
      the neurological departments by interdisciplinary teams with particular interest
      in motor neurone disease.

PMID- 7520643
TI  - [Controlled, clinical trial of isoprinosine administration to HIV-infected
      patients. Results of a Danish/Swedish multicenter study. The Scandinavian
      Isoprinosine Study Group].
AB  - The safety and efficacy of isoprinosine in HIV-infected individuals were assessed
      in a multicentre, randomized, double-blind, 24-week study phase, followed by an
      optional 24-week open treatment phase. The results of the double-blind phase have
      been reported separately. Of 866 HIV-seropositive individuals randomized, 832
      were eligible for efficacy analysis. On completion of the double-blind phase, 596
      patients started open treatment. All patients were evaluated with regard to
      progression to AIDS. Within 48 weeks, 10/412 patients (2.4%) assigned
      isoprinosine and 27/420 (6.4%) assigned placebo progressed to AIDS (p = 0.005;
      odds ratio: 2.8, 95% CI: 1.3-6.2). Intention-to-treat analysis showed identical
      results. No severe adverse reactions or toxicities were observed. We conclude
      that HIV-infected individuals without AIDS may be safely and effectively treated
      with isoprinosine.

PMID- 7520642
TI  - Prostatic marker-negative amphicrine carcinoma of the prostate.
AB  - It has been shown that prostatic adenocarcinoma differentiation correlates with
      prostatic-specific marker and neuroendocrine expression; that is, the more
      undifferentiated the tumor, the less it expresses prostatic markers and the more
      neuroendocrine cells are found in it. Complete absence of prostatic markers
      together with marked neuroendocrine expression has been associated with small
      cell morphology. This report describes a case of a metastatic, prostatic marker
      negative, non-small cell prostatic adenocarcinoma with a prominent neuroendocrine
      component. The architecturally well-organized luminal-exocrine cells appeared
      ultrastructurally undifferentiated, however, displaying an almost empty
      cytoplasm. This contrasted with the prostatic marker-positive control cases of
      prostatic carcinoma, which contained relatively numerous cytoplasmic vacuoles.
      The neuroendocrine cells could be identified by light microscopy as eosinophilic
      cells. The number of the latter cells was markedly increased in the metastatic
      foci compared with the primary tumor. Light microscopically and
      ultrastructurally, the eosinophilic cells in this case differed from the Paneth
      like cells described in prostatic carcinoma in previous reports. This case
      provides support for the general concept of multidirectional differentiation in
      human epithelial cancers and in particular for the association of poor tumor
      differentiation with neuroendocrine expression in prostatic carcinoma. In
      addition, in contrast with previous reports describing absence of basement
      membrane in metastatic foci of prostatic carcinoma, in the current case well
      formed basal laminae were identified.

PMID- 7520645
TI  - Inhibition of cytotoxicity of chicken granulocytes by serotonin and ketanserin.
AB  - Serotonin (5-HT) has been observed to impair the cytotoxicity of human natural
      killer (NK) cells. A study has now been made of the effect of 5-HT on the
      cytotoxic activity of chicken granulocytes. 5-HT at concentrations of 10(-3) to
      10(-6) M inhibited the cytotoxicity of chicken granulocytes when added at the
      onset of the short-term cytotoxicity assay. Ketanserin, a 5-HT2 receptor
      antagonist, did not reverse the inhibitory effect of 5-HT on chicken granulocyte
      cytotoxicity. Moreover, ketanserin at concentrations of 5 x 10(-4) to 5 x 10(-7)
      M inhibited the cytotoxicity mediated by chicken granulocytes. Pretreatment of
      the effector cells for 2 h with chick fibroblast interferon reduced the
      inhibition of chicken NK cytotoxicity induced by 5-HT and by ketanserin. These
      data indicate that, in birds, the neurotransmitter 5-HT serves as a link between
      the central nervous system and the immune system, and that interferon can
      modulate the inhibitory effect of 5-HT on the function of cytotoxic granulocytes.

PMID- 7520646
TI  - Quantitative characterization of the CD5 bearing lymphocyte population in the
      peripheral blood of normal sheep.
AB  - Quantitative characterization of the circulating CD5+ lymphocyte population in
      sheep was performed using monoclonal antibodies against ovine CD5, ovine CD2, and
      ovine sIgM. A total of fifteen sheep were examined biweekly over a period of 2.5
      months. The total CD5+ population was measured using single color flow cytometry,
      while CD5+ cells co-expressing sIgM or CD2 were determined by two color flow
      cytometric analysis. The total CD5+ cell population comprised 31.5-65.4% of gated
      lymphocytes with a mean value of 44.9%. Absolute CD5+ cell numbers varied from
      1075 to 8007 cells mm-3, with a mean value of 3149 cells mm-3. The mean
      proportion of CD5+ B-cells was 4.0%, with a mean absolute value of 270 cells mm
      3. The mean proportion of CD5+/CD2+ cells was 12.1% while that of CD5+/CD2- cells
      was 28.6%, corresponding to mean absolute values of 727 and 1794 cells mm-3
      respectively. Significant variation in CD5+ lymphocyte numbers in all individual
      animals occurred over the time span of the study. The results of this study
      provide a baseline from which to accurately assess CD5+ cell populations in
      neoplastic and infectious diseases.

PMID- 7520647
TI  - Infiltrating gamma delta T-cells and selectin endothelial ligands in the
      cutaneous phytohaemagglutinin-induced inflammatory reaction.
AB  - The 24 h phytohaemagglutinin-induced skin inflammatory site (intradermal and
      subcutaneous) was studied in inbred MHC-homozygous (SLAb/b) pigs and it was
      found, by immunohistology, that the predominant lymphocytes in the infiltrate are
      CD2-CD4-CD8-sIg-T-cells, the Null/gamma delta T-cell family, identified using the
      monoclonal antibodies (mAbs) MAC320 and MAC319 (which recognises a subset of
      MAC320+ cells). A large percentage of the infiltrating cells expressed the gamma
      delta T-cell receptor phenotype identified by binding of the mAb 86D. Fewer CD2+,
      CD8+ and CD4+ cells were present and surface immunoglobulin positive (sIg+) cells
      were virtually absent in the infiltrate. Areas of lymphocytic infiltration were
      associated with endothelial activation as determined by expression of the E
      selectin and a ligand for the L-selectin.

PMID- 7520648
TI  - National Ambulatory Medical Care Survey: 1991 summary.
AB  - Based on data collected from a national sample of office-based physicians,
      statistics are presented on the provision and utilization of ambulatory medical
      care services in physicians' offices during 1991. Ambulatory medical care
      services are described in terms of patient characteristics, physician practice
      characteristics, and visit characteristics.

PMID- 7520649
TI  - [The differential diagnostic significance of neutrophilic reactions to specific
      antigens in patients with pulmonary tuberculosis and sarcoidosis].
AB  - Similarity of clinical, roentgenological and even morphological features of
      tuberculosis and sarcoidosis causes difficulties in differential diagnosis. This
      necessitates searching for new diagnostic criteria. Comparative study of
      functional state of peripheral blood neutrophils and their reaction to specific
      antigens (tuberculin and Kveim's reagent) were studied in patients with
      disseminated tuberculosis and pulmonary sarcoidosis. Tuberculin was demonstrated
      to exert specific effects only in tuberculous patients. It stimulated migration
      and increased number of EAC-rosette-forming cells. Specific effects of Kveim's
      antigen were manifested by considerable increase of E-RFC number and decreased
      absorptive abilities of phagocytes in patients with sarcoidosis. Differences in
      effects of tuberculin and Kveim's antigen may be used for differential diagnosis
      of tuberculosis and sarcoidosis.

PMID- 7520650
TI  - [A chemical typhoid vaccine containing a surface-antigen complex including the K
      antigen].
AB  - A new chemical typhoid vaccine containing the complex of surface Vi- and K
      antigens has been obtained and experimentally studied. The vaccine has been found
      to possess high immunogenic and antigenic potency. Typhoid complex vaccine
      containing K-antigen stimulates the development of anti-infection and
      postvaccinal complex.

PMID- 7520651
TI  - [Protease inhibitors as immunomodulators in experimental acute pancreatitis and
      staphylococcal infection].
AB  - The influence of protease-inhibiting preparations on the development of humoral
      immune response in diseases involving the development of secondary
      immunodeficiency (experimentally induced acute pancreatitis and staphylococcal
      infection) has been studied. Five injections of contrycal and epsilon
      aminocaproic acid (epsilon-ACA), starting from day 1 after the induction of acute
      pancreatitis, normalized the immune response induced by sheep red blood cells 24
      hours after operation. In staphylococcal infection protease-inhibiting
      preparations (contrycal, epsilon-ACA, Amben) produced a protective effect,
      increasing the survival rate and the mean survival time of the animals infected
      with staphylococci.

PMID- 7520652
TI  - [The role of neuraminidase in the development of a dermonecrotic effect when
      Vibrio cholerae antigens are used].

PMID- 7520653
TI  - [Inducers of autoimmune reactions in patients with trigeminal neuralgia].
AB  - The antigenic determinants of proteins contained in normal nervous tissue and
      some microorganisms were studied by the method of immunoblotting. Nervous tissue
      was found to contain antigens, common with some Mycobacterium tuberculosis
      antigens having molecular weights (MW) of 104, 90, 68, 40, 34, 28 kD and some
      antigens contained in staphylococcal and streptococcal proteins with MW of 274,
      163, 63, 50 kD. In serum samples taken from trigeminal neuralgia patients
      autoantibodies to cross-reacting determinants of microbial and nerve proteins
      with MW of 84, 76, 66, 64, 44, 40, 38, 28 kD were detected. These autoantibodies
      were absent in the sera of healthy persons. The conclusion was made that the
      autoantibodies under study might play a certain role in the pathogenesis of pangs
      in such patients.

PMID- 7520654
TI  - [A highly sensitive, homogeneous method for determining antibodies and antigens
      by using liposomes, monoclonal antibodies and complement].
AB  - A simple and sensitive method for the determination of Francisella tularensis
      antigen and antibodies to this antigen by means of the complement lysis of
      liposomes sensitized with F. tularensis lipopolysaccharide (LPS) is proposed. The
      possibility of participation of monoclonal antibodies (McAb) in the complement
      dependent lysis of liposomes has been studied. The method permits the detection
      of 50-100 ng/ml of soluble LPS antigen in the presence of antiserum or McAb IgG F
      B11-x and of 50-10 ng/ml of it in the presence of IgG F-B11-x and anti-IgG within
      90 minutes.

PMID- 7520655
TI  - [The determination of the antigenic determinant of protective monoclonal
      antibodies specific to the Francisella tularensis lipopolysaccharide].
AB  - F. tularensis lipopolysaccharide (LPS) was studied with the use of monoclonal
      antibodies (McAb) having protective properties. The binding site of these McAb
      (IgG2a) is localized on the O-chain of LPS. In contrast to LPS isolated from
      vaccine strain 15, LPS isolated from F. tularensis cells in the R-form has no O
      chains and does not interact with McAb.

PMID- 7520656
TI  - [The detection of the Shiga toxin antigen in connection with other virulence
      factors--the O and K antigens of enterobacteria].
AB  - The results of the detection of Shiga toxin antigen in culture filtrates of 73
      enterobacterial strains by the methods of countercurrent electrophoresis and
      coagglutination, as well as their correlation with the presence of other factors
      of virulence, O- and K-antigens, have been analyzed. Sharply pronounced inverse
      correlation between the capacity of enterobacteria to synthesize Shiga (Shiga
      like) toxins and their capacity to synthesize acidic polysaccharide surface
      specific K- (Vi-) antigens has been established.

PMID- 7520657
TI  - [The isolation of an antigen, species-specific in immunochemical tests, from the
      culture broth of yeastlike fungi in the genus Candida].
AB  - In this work an antigen obtained from the culture fluid of C. tropicalis strain
      928 is described. The strain was cultivated in a synthetic culture medium in
      fermenters. The culture fluid was concentrated in cartridges and then on
      membranes. The concentrate was electrophoretically separated in an agar block.
      The isolated fraction was purified on Con-A Sepharose. The antigen thus obtained
      proved to be homogeneous in immunophoresis and in immunodiffusion with homologous
      serum to the culture fluid. In immunodiffusion and immunophoresis this purified
      fraction did not precipitate with sera to antigens obtained from the culture
      fluids of strains of other Candida species.

PMID- 7520658
TI  - [Interferon (IFN) in multiple myeloma and non-Hodgkin's lymphoma].
AB  - Interferon combined with cytostatics yielded in multiple myeloma more objective
      reactions than conventional chemotherapy. Survival time elongation was achieved
      solely by maintaining myeloma remissions with long term interferon
      administration. In non-Hodgkin's lymphoma combinations of cytostatics with
      interferon were more effective than conventional chemo-and radiotherapy only when
      used in low grade lymphomas of the nodular type. Evidence for longer survival of
      these patients still waits for presentation.

PMID- 7520660
TI  - Pharmacological background to decongesting and anti-inflammatory treatment of
      rhinitis and sinusitis.
AB  - A review is given of the literature concerning effects of oral and topical
      decongestants and anti-inflammatory drugs in rhinitis and sinusitis. Oral
      vasoconstrictors, effective in decongesting the nasal mucosa, need to be taken in
      doses that may induce disturbing systemic side-effects. Nonsteroidal anti
      inflammatory drugs (NSAIDs) have weak effects in allergic rhinitis as compared
      with glucocorticosteroids. No controlled clinical trials of systemic
      glucocorticosteroids in sinusitis have been published. Four studies in which
      different glucocorticosteroids were administered topically for sinusitis have
      been performed, but these gave very weak support for any positive effects of such
      a treatment.

PMID- 7520659
TI  - Effects of granulocyte colony-stimulating factor in children with severe
      neutropenia.
AB  - In children with all types of severe neutropenia the development of G-CSF for
      therapeutic use changed the quality of their life dramatically. Missing the most
      important cells in the defense against bacterial infections the neutrophilic
      granulocytes, these patients suffered from episodes of severe, often life
      threatening bacterial infections. They spent numerous days in hospital, requiring
      intravenous antibiotic treatment. Recurrence of bacterial infections at the same
      site led to irreversible tissue damage, for example in the lung, requiring often
      disabling surgical interventions. In most patients G-CSF treatment induced an
      increase of blood and tissue neutrophils to a level high enough to guarantee a
      normal defense against bacterial infections. The quality of life improved
      substantially in these children. The fact that they have to inject themselves
      daily does not cause any problems. Overall, taken in consideration all possible
      adverse events during our short observation period, all patients who responded to
      G-CSF benefit from this treatment to a degree never considered to be possible
      before.

PMID- 7520661
TI  - Investigations on allergogenic properties of Tolpa Peat Preparation.
AB  - The ability of Tolpa Peat Preparation (TPP) to induce or enhance an allergic
      sensitization was tested on mice and guinea pigs. The levels of IgE antibody in
      the mouse sera and IgG1 as well as IgE antibody levels in guinea pig sera were
      evaluated by PCA (Passive Cutaneous Anaphylaxis) tests. TPP adsorbed on aluminium
      hydroxide gel (alum) and introduced into BALB/c mice by several subcutaneous
      injections was unable to stimulate the noticeable anti-TPP IgE antibody response.
      TPP introduced together with ovalbumin (OA) into the mice in the course of
      immunization with OA did not enhance anti-OA IgE antibody response. TPP adsorbed
      on alum and injected subcutaneously into guinea pigs was unable to induce
      noticeable IgG1a, IgG1b and IgE antibody response, and mast cells obtained from
      lung and mesentery of these animals did not release histamine when challenged
      with TPP in vitro at 37 degrees C. In conclusion, our results show that under the
      experimental conditions used in the present experiments TPP was unable to induce
      or enhance an allergic sensitization of mice and guinea pigs.

PMID- 7520662
TI  - Influence of Tolpa Peat Preparation on the IgE-induced anaphylactic reactions in
      mice.
AB  - The ability of Tolpa Peat Preparation (TPP) to affect anaphylactic sensitization
      and mast cell secretory function was tested in BALB/c mice treated with TPP
      orally for 12 days. TPP in the doses of 20 and 50 mg/kg/day reduced histamine
      release from mouse peritoneal mast cells challenged with anti-IgE or concanavalin
      A in vitro. The treatment of mice with TPP from day 1 to day 12 of immunization
      with Ovalbumin (OA) absorbed on aluminium hydroxide gel resulted in a decrease of
      antigen-induced histamine release from mast cells of these mice in vitro and in
      decreased IgE antibody level in their sera. TPP introduced into OA-immunized mice
      showing developed IgE antibody response was less effective in decreasing
      anaphylactic histamine release from mast cells of these mice. In all experiments
      low doses of TPP used for oral treatment were more effective than high doses in
      inhibiting anaphylactic events in the mice.

PMID- 7520663
TI  - Evidence for nutrient modulation of tumor phenotype: impact of tyrosine and
      phenylalanine restriction.
AB  - We have shown that Tyr and Phe restriction suppresses the malignant phenotype of
      the highly invasive and metastatic BL6 variant of B16 murine melanoma. Lung
      colonizing abilities of Tyr- and Phe-modulated in vivo and in vitro variants of
      BL6 are inhibited following intravenous inoculation into mice fed normal diet.
      Although this antimetastatic effect of Tyr and Phe restriction is most likely not
      due to differences in attachment to endothelium, our data indicate that major
      impacts of Tyr and Phe restriction are at the level of the tumor, itself.
      Modulation of host immune responses, which in turn suppresses metastasis, does
      not appear to contribute significantly to the altered phenotype. Although numbers
      and function of T cells, mast cells, and NK cells are affected by Tyr and Phe
      restriction, they are not involved in the Tyr- and Phe-mediated suppression of
      tumor growth, metastasis, or angiogenesis. Our data do not rule out the
      importance of other host factors involved in the Tyr and Phe modulation of tumor
      phenotype. The outcome of this modulation results most likely from complex
      Tyr/Phe-tumor-host interactions.

PMID- 7520664
TI  - Alteration in the antigenic structure of M1 protein of influenza A virus mutant
      resistant to a new antiviral compound mopyridone.
AB  - Using 14 monoclonal antibodies (MoAbs) in solid-phase ELISA it was found that
      influenza virus A/Hong Kong/1/68 (H3N2) mutants resistant to the antiviral
      compound mopyridone as compared to the mopyridone-sensitive mutant manifested
      significant changes in the antigenic structure (sites 1A, 2 and 3) of M1 protein.
      No differences in M1 were found between rimantadine-resistant and rimantadine
      sensitive mutants of influenza virus A(H3N2).

PMID- 7520665
TI  - Effect of sera of cirrhotic patients with or without hepatitis B virus infection
      on protein synthesis in hepatoma cells.
AB  - The in vitro effects of sera of 11 patients with liver cirrhosis on protein
      synthesis in PLC/PRF/5 cells were studied. Hepatitis B virus (HBV) infection was
      documented in 7 patients. Increased random production of several cell proteins of
      M(r) of approximately 25, 65, 90 and 130 K was shown by SDS-polyacrylamide gel
      electrophoresis (SDS-PAGE). There was no correlation between HBV-positive and HBV
      negative cirrhosis and the induced proteins. One of them was identified as alpha
      1 foetoprotein by immunoblot analysis. C-reactive protein (CRP) was determined
      only in one case; production of interleukin-6 (IL-6) was not detected.

PMID- 7520666
TI  - The ratio of defective HIV-1 particles to replication-competent infectious
      virions.
AB  - The ratio of infectious to defective particles has been investigated for human
      immunodeficiency virus type 1 (HIV-1). Although the concentration of HIV core p24
      protein defined by ELISA permits the estimation of a total number of average
      sized HIV particles, it does not provide information on the numerical value of
      infectious particles. This problem was addressed by limiting dilution of viral
      supernatant derived from various infected cell lines and then comparing the total
      number of HIV particles to the end-point titers of viral inoculum determined by
      reverse transcriptase assay and virus-induced cytotoxicity. The results indicate
      that the ratio of infectious to defective virus particles varies for different
      virus strains and host cells within a range from 1:1 to 1:100, but for given
      virus-cell system it remains constant.

PMID- 7520667
TI  - Neurobehavioral assessment of high-risk infants in the neonatal intensive care
      unit.
AB  - Neurobehavioral organization describes infants' abilities to organize themselves
      within their central nervous system maturation and environment. As part of
      infants' environment, caregivers can structure the environment to support
      infants' development. Care of the high-risk infant emphasizes support of infants'
      emerging neurobehavioral organization. This article describes the theoretical
      rationale of neurobehavioral organization, effect on the infant and family, and
      assessments available to the neonatal occupational therapist for use with high
      risk infants. Information gained via neurobehavioral assessment can be used to
      engage parents in better understanding their infant's behaviors and interact at a
      level appropriate with their infant.

PMID- 7520668
TI  - Localization and regulation of endothelial NO synthase mRNA expression in rat
      kidney.
AB  - Nitric oxide (NO) has effects on renal blood flow, glomerular filtration rate,
      renin secretion, and renal sodium excretion. Four isoforms of nitric oxide
      synthase (NOS) have been cloned to date. However, the molecular identity of NOS
      present in the renal vasculature is unknown. Endothelial NOS (NOS-III) is
      regulated both acutely by cell calcium and chronically by shear stress. To
      determine if renal blood vessels and the glomerulus express NOS-III mRNA, we used
      degenerate polymerase chain reaction (PCR) to clone a portion of rat NOS-III. We
      then assayed NOS-III mRNA in microdissected renal structures by reverse
      transcriptase-PCR. NOS-III mRNA was expressed at high levels in glomeruli,
      arcuate vessels, and interlobular artery/afferent arterioles. NOS-III mRNA was
      detected inconsistently in proximal tubules, thick ascending limbs, and cortical
      and inner medullary collecting ducts. Previous studies have shown that chronic
      oral treatment with the NOS inhibitor N omega-nitro-L-arginine methyl ester (L
      NAME) decreases NO synthesis and causes hypertension. To determine if the
      systemic blockade occurs only by competitive inhibition, we determined the effect
      of L-NAME on glomerular NOS-III mRNA. L-NAME administration (5 days) decreased
      NOS-III mRNA in the glomerulus to 25 +/- 12% of control levels. We conclude that
      endothelial NOS-III mRNA is preferentially expressed in the glomerulus and renal
      vasculature, where it can modulate renal blood flow and glomerular filtration
      rate. Furthermore, glomerular NOS-III may be modulated at the level of mRNA
      abundance in vivo by systemic L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520669
TI  - Expression of plasminogen/plasmin receptors on human glomerular epithelial cells.
AB  - The aim of the present study was to display plasminogen/plasmin receptors on
      human glomerular epithelial cell (HGEC) membranes and to determine the properties
      of receptor-bound plasminogen at the cell surface. Using an immortalized human
      glomerular epithelial cell line (E71-A1), we found a specific, saturable, and
      reversible binding of 125I-labeled plasminogen and 125I-labeled plasmin to HGEC
      that involved the lysine binding sites of both ligands. 125I-plasminogen and 125I
      plasmin bound to the same receptors with different affinities: Kd = 1.20 +/- 0.08
      and 0.30 +/- 0.05 microM, respectively (P < 0.001). The number of binding sites
      per cell was 6.00 +/- 0.56 x 10(6) for plasminogen and 2.00 +/- 0.47 x 10(6) for
      plasmin (P < 0.05). Similar receptor affinities were found on isolated glomeruli,
      on immortalized and nonimmortalized HGEC, and on purified HGEC membranes. The
      apparent kinetic constants of plasminogen activation by receptor-bound urokinase
      type plasminogen activator (u-PA) compared with solution-phase u-PA [Michaelis
      constant (Km) = 0.80 +/- 0.54 vs. 3.15 +/- 0.78 microM, P < 0.0001; catalytic
      constant (kcat) = 0.39 +/- 0.17 vs. 0.50 +/- 0.29 s-1, not significant; kcat/Km =
      0.57 +/- 0.35 vs. 0.16 +/- 0.11 microM-1.s-1, P < 0.05, respectively] showed a
      higher efficiency of plasminogen activation at the cell surface. When measured by
      a chromogenic assay using S22-51, receptor-bound plasmin activity on HGEC was
      partly protected from its inhibitor, alpha-2-antiplasmin, whereas solution-phase
      plasmin was not.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520670
TI  - Role of P-selectin in microvascular leukocyte-endothelial interaction in
      splanchnic ischemia-reperfusion.
AB  - The role of P-selectin in leukocyte-endothelial interaction after splanchnic
      arterial occlusion and reperfusion (SAO/R) in pentobarbital-anesthetized rats was
      investigated employing a P-selectin-neutralizing monoclonal antibody (i.e., MAb
      PB1.3). MAb PB1.3 (1 mg/kg) given intravenously to SAO/R rats just before
      reperfusion significantly attenuated leukocyte rolling and adherence in
      mesenteric postcapillary venules as observed via intravital microscopy. Likewise,
      ileal myeloperoxidase (MPO) activity was decreased from 4.6 +/- 0.6 in nontreated
      ischemic rats to 2.0 +/- 0.2 U/100 mg (P < 0.01), indicating a lesser degree of
      polymorphonuclear leukocyte (PMN) accumulation. A significantly lower plasma free
      amino-nitrogen concentration was observed in MAb PB1.3-treated rats vs. untreated
      (P < 0.01), suggesting decreased tissue injury after reperfusion.
      Immunohistochemical localization demonstrated significant expression of P
      selectin in endothelial cells lining ileal postcapillary venules 30 min after
      reperfusion of the ischemic splanchnic circulation. Thus P-selectin appears to
      plays an important role in leukocyte accumulation after splanchnic ischemia
      reperfusion, and the MAb PB1.3 attenuates the accumulation of PMNs in the
      ischemic-reperfused small bowel, resulting in reduced tissue injury.

PMID- 7520671
TI  - N-methyl-D-aspartate induces phase shifts in circadian rhythm of neuronal
      activity of rat SCN in vitro.
AB  - The suprachiasmatic nucleus (SCN) acts as a pacemaker for mammalian circadian
      rhythms. Receptors for excitatory amino acids like N-methyl-D-aspartate (NMDA)
      and non-NMDA receptors have both been found to play an important role in the
      transmission of photic information from the retina to the SCN. Therefore, we
      investigated whether the application of glutamate receptor agonists could reset
      the phase of the circadian rhythm of SCN firing activity in vitro. Treatment with
      NMDA (0.1-10 microM) for 15 min or 1 h during the early part of the subjective
      night produced phase delay, whereas treatment during the late subjective night
      caused an advance in phase. The phase-response curve for NMDA was similar to that
      previously obtained in response to light pulses in vivo. Application of DL-alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) (1 or 10
      microM), a non-NMDA-receptor agonist, also produced a dose-dependent phase delay
      of SCN activity. The NMDA-induced phase delay was antagonized by an NMDA-receptor
      antagonist MK-801. These findings suggest that both NMDA and non-NMDA receptors
      may be involved in the transmission of information to the SCN via the
      retinohypothalamic tract. In addition, both the advances and delays in phase
      caused by NMDA were potentiated by cotreatment with neuropeptide Y, whereas AMPA
      induced phase delay was not potentiated by neuropeptide Y. This points to a
      functional link between NMDA and neuropeptide Y receptor-mediated mechanisms in
      the SCN.

PMID- 7520672
TI  - Response to clozapine as a predictor of risperidone response in schizophrenia.

PMID- 7520673
TI  - Adenosis of the prostate. Histologic features in transurethral resection
      specimens.
AB  - Adenosis (atypical adenomatous hyperplasia, small gland hyperplasia) of the
      prostate is characterized by a relatively well-circumscribed proliferation of
      benign glands that frequently mimics low-grade adenocarcinoma. Although general
      reviews of adenosis exist, relatively few specialized studies have characterized
      the histologic features of adenosis. The purpose of this study was to review and
      better document the histologic features of adenosis. Forty-four transurethral
      resection (TUR) specimens containing a total of 145 foci of adenosis were
      evaluated for the presence or absence of six histologic features: mitotic
      figures, blue-tinged luminal mucinous secretions, intraluminal crystalloids,
      single cells, a focally infiltrative growth pattern, and prominent nucleoli.
      Immunohistochemical stains for high-molecular-weight cytokeratin were performed
      on 66 (46%) of the foci to confirm the presence of a basal cell layer and thus
      the diagnosis of adenosis. Crystalloids were present in 58 foci (40%), an
      infiltrative growth pattern in 27 foci (19%), single cells in 23 foci (16%),
      prominent nucleoli in 22 foci (15%), mitotic figures in 16 foci (11%), and blue
      tinged luminal mucinous secretions in 3 foci (2%). The diagnosis of adenosis is
      based on a constellation of histologic features and may be confirmed with the use
      of antibodies to high-molecular-weight cytokeratin.

PMID- 7520674
TI  - Use of molybdenum telluride as a substrate for the imaging of biological
      molecules during scanning tunnelling microscopy.
AB  - Scanning tunnelling microscopy was used to image biological molecules including
      supercoiled deoxyribonacetic acid and specific retrovirus enzymes, the reverse
      transcriptases of the avian myeloblastosis virus, the moloney murine leukaemia
      virus and the human immunodeficiency virus. Measurements were carried out on
      graphite and Group VI transition metal dichalcogenide layered crystals. Images
      obtained with graphite could not be unequivocally interpreted and attachment
      appears to occur solely at surface defect sites. The layered crystal MoTe2 shows
      different imaging properties. The bimolecules are clearly visible, distributed
      over the semiconductor surface, and the molecular shapes and dimensions show good
      correlation with structure predictions.

PMID- 7520675
TI  - Is sodium acetate dextran superior to sodium chloride dextran for small volume
      resuscitation from traumatic hemorrhagic shock?
AB  - Small volumes (4 mL/kg body weight (bw)) of hypertonic sodium chloride dextran
      effectively restore cardiac output and nutritional blood flow and increase
      arterial pressure in severe hemorrhagic shock. It has been suggested that the
      chloride anion be replaced with acetate to provide a solution that avoids the
      risk of hyperchloremia and has the advantage of supplying a buffering base to
      optimize hypertonic resuscitation. This study compares the effects of hypertonic
      sodium chloride dextran solution (7.2% NaCl/10% dextran 60 [NaCl-Dx]; n = 7) with
      sodium acetate dextran (10.4% Na-Ac/10% dextran 60 [NaAc-Dx]; n = 6) on
      hemodynamic, oxygen transport, and metabolic variables. Both solutions had the
      identical osmolality (2400 mOsmol/kg). Dogs (16.9 +/- 1.9 kg) were anesthetized
      and mechanically ventilated. Shock was induced by exteriorization of intestine
      and blood withdrawal (50% of blood volume) to maintain mean arterial blood
      pressure (MAP) at 40 mm Hg for 75 min. Thereafter, resuscitation was performed
      either with NaCl-Dx (4 mL/kg over 2 min) or NaAc-Dx (4 mL/kg over 4 min). During
      hypertonic resuscitation, there was a short-lasting decrease in MAP, which was
      more pronounced in the NaAc-Dx group (delta MAP -7.3 +/- 2.5 mm Hg). Cardiac
      index and oxygen consumption were normalized within 5 min after resuscitation
      with both solutions. In NaAc-Dx-treated animals, MAP remained at lower values as
      compared to NaCl-Dx-treated dogs at 5 and 30 min after resuscitation (52 +/- 3 vs
      74 +/- 6, and 61 +/- 7 vs 79 +/- 12 mm Hg; P < 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7520676
TI  - Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double
      blind, placebo-controlled trial.
AB  - OBJECTIVE: To determine if filgrastim (recombinant human methionyl granulocyte
      colony-stimulating factor) used in addition to standard inpatient antibiotic
      therapy accelerated recovery from infection associated with chemotherapy-induced
      neutropenia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING:
      Hematology and oncology wards of four teaching hospitals. PATIENTS: 218 patients
      with cancer who had fever (temperature > 38.2 degrees C) and neutropenia
      (neutrophil count < 1.0 x 10(9)/L) after chemotherapy. INTERVENTION: Patients
      were randomly assigned to receive filgrastim (12 micrograms/kg of body weight per
      day) (n = 109) or placebo (n = 107) beginning within 12 hours of empiric therapy
      with tobramycin and piperacillin. Patients received treatment and remained in the
      study until the neutrophil count was greater than 0.5 x 10(9)/L and until 4 days
      without fever (temperature < 37.5 degrees C) had elapsed. MEASUREMENTS: Days of
      neutropenia and fever and days in the study (hospitalization); time to resolution
      of fever and febrile neutropenia; and frequency of the use of alternative
      antibiotics. RESULTS: Compared with placebo, filgrastim reduced the median number
      of days of neutropenia (3.0 compared with 4.0 days of a neutrophil count of < 0.5
      x 10(9)/L; P = 0.005) and the time to resolution of febrile neutropenia (5.0
      compared with 6.0 days; P = 0.01) but not days of fever (3.0 days for both
      groups). The frequency of the use of alternative antibiotics was similar in the
      two groups (46% compared with 41%; P = 0.48). The median number of days patients
      were hospitalized while on study was the same (8.0 days; P = 0.09); however,
      filgrastim decreased the risk for prolonged hospitalization (> 11 days, 4th
      quartile) by half (relative risk, 2.1 [95% CI, 1.1 to 4.1]; P = 0.02). In
      exploratory subset analyses, filgrastim appeared to provide the greatest benefit
      in patients with documented infection and in patients presenting with neutrophil
      counts of less than 0.1 x 10(9)/L. CONCLUSIONS: Filgrastim treatment used with
      antibiotics at the onset of febrile neutropenia in patients with cancer who have
      received chemotherapy accelerated neutrophil recovery and shortened the duration
      of febrile neutropenia.

PMID- 7520677
TI  - Growth factors and empiric therapy with antibiotics: should they be used
      concurrently?

PMID- 7520678
TI  - The measurement of 5-hydroxyindoleacetic acid in urine.

PMID- 7520680
TI  - The identification, isolation and characterization of a 67 kilodalton, PNA
      reactive autoantigen commonly expressed in human adenocarcinomas.
AB  - In an attempt to characterize a Peanut Agglutinin (PNA) autoantigen widely
      expressed in common human adenocarcinomas, monoclonal antibodies (MAbs) were made
      against PNA-affinity purified glycoproteins from pooled breast cancer membrane
      biopsy materials. Two IgM MAbs, 167H.1 and 167H.4, were found to react strongly
      with frozen tissue sections of various adenocarcinomas and the antigen was
      characterized further. By immunoprecipitation, western blotting, and gel
      filtration, both MAbs were found to react with a 67 kilodalton (kD) antigen. The
      67 kD antigen was purified and determined to be specifically PNA reactive and
      naturally occurring antibodies were demonstrated to the purified antigen. In
      conclusion, the 167H.1 and 167H.4 MAbs identify a non-mucinous, PNA-reactive
      autoantigen widely expressed in human adenocarcinomas.

PMID- 7520679
TI  - Normal serum alpha-fetoprotein in acute hepatic porphyria.

PMID- 7520681
TI  - Dose escalation of dacarbazine combined with interferon alpha-2a, G-CSF and
      ondansetron in patients with metastatic melanoma.
AB  - To define the activity of an individually escalated dacarbazine (DTIC) dose
      combined with interferon-alpha-2a (IFN), granulocyte-colony stimulating-factor (G
      CSF) and ondansetron, 20 patients (pts) with metastatic melanoma were treated
      with DTIC, ondansetron 8 mg iv, G-CSF 300 micrograms sc and IFN 9 MU sc.
      Treatment was performed every 21 days to a maximum of 6 courses. DTIC dose was
      escalated with 250 mg/m2 in case of acceptable toxicity to 1250, 1500 and 1750
      mg/m2 in (projected/realized), 14/19, 8/11 and 0/5 pts, respectively. Dose
      escalation prohibiting toxicities were thrombocytopenia (10 pts), leukopenia (9
      pts), and nausea/vomiting (2 pts). Four partial remissions were observed, for a
      response rate of 20% (95% confidence interval, 6 to 44%). Duration of responses
      was 1, 2, 3 and 3 months. Median overall survival was 8 months.

PMID- 7520682
TI  - Determination of serum levels of different cytokeratins in patients with uterine
      malignancies.
AB  - Tissue polypeptide antigen (TPA), TPS, Cyfra 21-1, Cytokeratins 8-18 (CTKRS 8
      18), SCC and CA 125 were measured in blood samples drawn at diagnosis from 43
      patients with endometrial cancer, 47 with cervical cancer, 11 with cervical
      intraepithelial neoplasia (CIN), and 236 with benign uterine disease as controls.
      The cut-off values for all antigens were chosen at the 95th percentile of the
      standard Gaussian variate of controls; these limits were 98 U/L for TPA, 127 U/L
      for TPS, 1.6 ng/mL for Cyfra 21-1, 1.2 ng/mL for CTKRS 8-18, 48 U/mL for CA 125,
      and 2.8 ng/mL for SCC. TPA had the same sensitivity as SCC for squamous cell
      carcinoma of the cervix (42%) and a higher sensitivity than CA 125 for
      endometrial cancer (40% vs 12% respectively). TPA was more sensitive than TPS for
      both cervical (40% vs 13%) and endometrial cancer (40% vs 21%). TPA and SCC had a
      higher sensitivity than Cyfra 21-1 (34%) and CTKRS 8-18 (27%) for squamous cell
      carcinoma of the cervix. In conclusion, as for soluble cytokeratin fragments, the
      serum TPA seems to be the most reliable marker for the management of cervical and
      endometrial cancer.

PMID- 7520684
TI  - Effect of cardiopulmonary bypass on the circulating level of soluble GMP-140.
AB  - Soluble GMP-140 can prevent the adhesion of activated neutrophils to endothelium
      in vitro. Because cardiopulmonary bypass causes neutrophil-endothelial
      interaction, the plasma level of soluble GMP-140 was measured using an enzyme
      immunoassay system in 32 children undergoing intracardiac repair of congenital
      heart disease. They had either a high, low, or normal pulmonary blood flow (n =
      13, 12, and 7 respectively). Because activated platelets are a source of GMP-140,
      the plasma beta-thromboglobulin level was also measured. Blood was sampled
      before, during, and for 24 hours after cardiopulmonary bypass. Plasma levels of
      both soluble GMP-140 and beta-thromboglobulin increased after the onset of
      cardiopulmonary bypass in all patients but for both substances the increase was
      greater in those with a low pulmonary blood flow (p < 0.05 for all comparisons).
      The sum total of soluble GMP-140 values during and after operation was correlated
      negatively with the preoperative mean pulmonary arterial pressure (p < 0.05 for
      all time intervals). GMP-140 level correlated with the plasma beta
      thromboglobulin level (r = 0.5, p < 0.05). This work supports the contention that
      soluble GMP-140 is released from activated platelets during cardiopulmonary
      bypass, the level being particularly high in those who had intrinsically abnormal
      platelets preoperatively in association with a low pulmonary blood flow. Patients
      with a high pulmonary blood flow, who are more susceptible to endothelial cell
      injury, may be less well protected by soluble GMP-140.

PMID- 7520683
TI  - Effects of 2',3'-dideoxynucleosides on proliferation and differentiation of human
      pluripotent progenitors in liquid culture and their effects on mitochondrial DNA
      synthesis.
AB  - 2',3'-Dideoxynucleosides (ddNs) including 3'-azido-3'-deoxythymidine (AZT), 3'
      fluoro-3'-deoxythymidine (FLT), 3'-amino-3'-deoxythymidine (AMT), 2',3'
      dideoxycytidine (ddC), and 2',3'-didehydro-3'-deoxythymidine (D4T) were tested
      for their effects on proliferation and differentiation of pluripotent progenitor
      cells (CD34+) purified from human bone marrow cells grown in liquid cultures.
      These highly purified progenitor cells undergo extensive proliferation during 14
      days, with a marked differentiation during the last 7 days. These differentiated
      cells exhibit normal morphological features in response to specific hematopoietic
      growth factors of both erythroid and granulocyte-macrophage lineages, as
      demonstrated by flow cytometry cell phenotyping. The potencies of these ddNs in
      inhibiting proliferation of granulocyte-macrophage lineage cells were in the
      order FLT > AMT = ddC > AZT >> D4T, and the potencies in inhibiting proliferation
      of erythroid lineage cultures were in the order FLT > AMT > AZT > ddC >> D4T. The
      toxic effects of ddNs assessed in these liquid cultures were in agreement with
      data obtained by using semisolid cultures, demonstrating the consistency of these
      two in vitro hematopoietic systems toward ddN toxicity. ddC was toxic to CD34+
      progenitor cells and/or cells in the early stages of differentiation, whereas the
      inhibitory effect of AZT on the erythroid lineage was predominantly observed on a
      more mature population of erythroid progenitors during the differentiation
      process. Slot blot analysis of granulocyte-macrophage cultures demonstrated that
      exposure to ddC and FLT was associated with a decrease in total mitochondrial DNA
      (mtDNA) content, suggesting that these two ddNs inhibit mtDNA synthesis. In
      contrast, no difference in the ratio of nuclear DNA to mtDNA was observed in
      cells exposed to toxic concentrations of AZT and AMT is not associated with an
      inhibition of mtDNA synthesis. This human pluripotent progenitor liquid culture
      system should permit detailed investigations of the cellular and molecular events
      involved in ddN-induced hematological toxicity.

PMID- 7520685
TI  - A short course of FK506 can induce limited donor-specific graft acceptance.
AB  - To examine the hypothesis that a short course of FK506 would induce permanent
      graft acceptance after lung transplantation, left lung allotransplantation was
      performed in 14 mongrel dogs. In group 1 (control; n = 3), no immunosuppressive
      agent was given. In group 2 (n = 7), FK506 (1.2 mg/kg intramuscularly) was given
      on posttransplantation days 0, 1, and 2. In group 3 (n = 4), FK506 was given at
      the same dose on posttransplantation days 0, 1, and 2 as well as on days 29 and
      30. Allograft function was evaluated by temporarily occluding the right pulmonary
      artery. A mixed lymphocyte reaction study was performed preoperatively and
      monthly thereafter. Control lungs were all rejected within 8 days. Group 2 dogs
      showed improved survival, with a median survival of 49.5 days. One dog in group 2
      lived more than 400 days after transplantation. The mixed lymphocyte reaction
      data suggests that some donor-specific unresponsiveness occurs, which lasts for
      only a limited time. Supplemental doses of FK506 did not significantly improve
      survival (median, 74 days). The whole blood level of FK506 was 17.7 +/- 3.98
      ng/mL on day 15; however, on day 29 the FK506 level was almost undetectable. We
      conclude that a 3-day course of 1.2 mg/kg of FK506 can induce donor-specific
      graft acceptance, but this acceptance is not permanent.

PMID- 7520686
TI  - Neutralization of heparin by Trasylol.

PMID- 7520687
TI  - Safety of aprotinin in profound hypothermia and circulatory arrest.

PMID- 7520688
TI  - Low-molecular-size allergens, LM-1s, in feces extract of Dermatophagoides farinae
      which elicit histamine release from washed blood cells of patients with bronchial
      asthma.
AB  - A significant activity to elicit histamine release was found in an
      ultrafilterable (Mr-cutoff < 10 kD) fraction of a mite feces extract from a spent
      mite medium. The activity was divided into two fractions (LM1 and LM2) on an
      Ultrogel AcA 54 column when monitored by histamine release assay using washed
      peripheral blood cells from mite-allergic patients. The larger-molecular-size
      antigen, LM1 was further separated into three allergenic fractions by consecutive
      chromatography on Sephadex G-50, GM-DEAE, and TSKgel ODS-120T. All the purified
      allergens, LM1s (LM1a, LM1b, and LM1c), which produced positive reactions in skin
      tests on allergic patients, were glycoproteins (molecular weight: 8 kD on SDS
      PAGE; 12.5 kD on Gel filtration) with different carbohydrate contents and pI
      values ranging from 4 to 5 on an IEF plate. LM1s were cross-reactive with anti
      Der f II but not with anti-Der f I. The reaction of LM1c to anti-Der f II serum
      was completely inhibited with the other antigens, while the reactions of LM1a and
      LM1b to the serum were partially inhibited with LM1c or the other antigens,
      respectively.

PMID- 7520689
TI  - Effects of various drugs (staurosporine, herbimycin A, ketotifen, theophylline,
      FK506 and cyclosporin A) on eosinophil viability.
AB  - Eosinophils are known to play an important role in the pathogenesis of asthma and
      other allergic diseases. This study demonstrated the effects of various drugs on
      eosinophil viability in vitro, which might help clinicians and researchers in
      treating and studying eosinophilic diseases. Staurosporine, a protein kinase C
      inhibitor, and herbimycin A, a tyrosine kinase inhibitor, at 10(-6) M and 10(-7)
      M significantly lowered eosinophil viability in a dose-dependent fashion (p <
      0.002, p < 0.02 and p < 0.001, p < 0.002, respectively). Both staurosporine and
      herbimycin A reduced eosinophil survival in a time-dependent fashion at 10(-6) M
      and 10(-7) M. Ketotifen at 10(-4) M and theophylline at 10(-3) M, significantly
      decreased eosinophil viability (p < 0.001 and p < 0.001, respectively) in the
      presence of 100 pg/ml of recombinant human interleukin-5 (rhIL-5). Both FK506 and
      cyclosporin A at 10(-4) M significantly reduced eosinophil viability (p < 0.001
      and p < 0.005, respectively) in the presence of 100 pg/ml of rhIL-5. Our data
      show that ketotifen, theophylline, FK506, cyclosporin A reduced eosinophil
      viability at a high concentration. Furthermore, it is suggested that protein
      kinase C and tyrosine kinase are involved in eosinophil survival.

PMID- 7520690
TI  - The effect of intraperitoneal N-methyl-N-nitrosourea on hamster palatal gingiva
      and intermolar mucosa.
AB  - Fifty 4- to 6-week-old male random-bred golden hamsters were injected
      intraperitoneally with a weight-related dose (12.5 mg/kg body weight) of N-methyl
      N-nitrosourea (NMU) three times a week for 4 weeks. Groups of seven animals were
      killed 10, 16 and 22 weeks after the first injection. The palatal gingiva from
      six animals and the intermolar mucosa from 21 animals was examined. Seven male
      age-matched untreated control animals were killed at each period. Although all
      NMU-treated hamsters showed dysplastic and neoplastic changes similar to those in
      human oral squamous-cell carcinoma, other changes such as acantholytic
      dyskeratosis, invading cysts, duct-like structures and basaloid islands and cords
      were not. The extent and severity of the changes increased with time so that by
      22 weeks there was extensive involvement of the palatal bone and marrow spaces,
      the molar periodontal ligament and the greater palatine neurovascular bundle by
      neoplastic epithelium. The invading epithelium was derived from the junctional,
      crevicular and palatal gingival and intermolar epithelium. The latent period for
      the crevicular and junctional epithelia was shorter than that for the palatal
      gingival and intermolar epithelium. The invasive changes from the latter
      epithelium were often preceded by exophytic changes such as epithelial
      projections, papillae and papillomas. Such changes were infrequent for the
      gingival, crevicular and junctional epithelia. The study shows that
      intraperitoneal NMU acts as a complete carcinogen on the palatal gingival and
      intermolar epithelium in hamsters.

PMID- 7520691
TI  - A drive to play: evolution and psychotherapeutic theory.
AB  - Freud's thinking was influenced by evolutionary ideas. He built his theory about
      the instincts of sexuality and aggression. A third phylogenetically given
      propensity for behaviour, that of attachment, has been added to traditional
      theory following the work of Bowlby. We propose that the origins of certain
      psychiatric disturbances, most notably cluster B personality disorders, are to be
      found not in those drives which are ancient in evolutionary terms but through a
      disruption of that which has been most recently evolved, and which involves
      symbolization. It is manifest developmentally as symbolic play. A case report
      illustrates the hypothesis.

PMID- 7520692
TI  - Identification of two elements involved in regulating expression of the murine
      leukaemia inhibitory factor gene.
AB  - Mouse leukaemia inhibitory factor (LIF) is a polyfunctional cytokine which
      exhibits multiple functions in vitro and in vivo. Two forms of LIF cDNA,
      differing at their 5' ends, have been described encoding either diffusible (D
      LIF) or matrix-associated (M-LIF) forms of the protein [Rathjen, Toth, Willis,
      Heath and Smith (1990) (Cell 62, 1105-1114]. The present report describes the DNA
      sequence and functional characterization of the murine LIF gene and its
      surrounding transcriptional regulatory elements. Transient transfection of
      constructs containing the LIF gene and various amounts of 5'-non-coding sequence
      failed to give detectable levels of expression, suggesting the presence of
      inhibitory sequences within the LIF gene. Stable cell lines were produced by
      transfection of experimental constructs containing various lengths of 5'-non
      coding sequence of the LIF gene, or the heterologous phosphoglycerate kinase
      promoter, linked to an LIF/neomycin-resistance-hybrid-coding sequence. The
      frequency of recovery of stable clones indicated that sequences located in the
      first intron between the transcriptional start sites for D-LIF and M-LIF act to
      suppress expression of the gene in most genomic locations. This region is rich in
      GC residues and has been shown to be hypomethylated in vitro [Kaspar, Dvorak and
      Bartunek (1993) FEBS Lett. 319, 159-162]. Analysis of the LIF/neomycin-resistance
      transgene expression in these stable cell clones demonstrated that transcripts
      containing the M-LIF or D-LIF exons required the presence of sequences located
      between -1200 and -3200 in the LIF gene. In the absence of these sequences,
      transcription is initiated elsewhere within the first intron. These sequences can
      be replaced by the heterologous phosphoglycerate kinase promoter. Deletion of the
      GC-rich region between the D-LIF and M-LIF transcriptional start sites results in
      the appearance of transcripts that do not splice out the first intron of the LIF
      gene. These may result from gene or promoter trapping of the LIF gene. Sequence
      analysis of the region between -1200 and -3200 revealed a number of minimal
      steroid-response elements, regions of similarity to DNAase I-hypersensitive sites
      in the uteroglobin gene and a region of alternating purine/pyrimidine sequence.
      This study therefore defines two important regulatory regions in the LIF gene: a
      GC-rich region in the first intron and a distal 'enhancer' located between -3200
      and -1200.

PMID- 7520693
TI  - Inhibition of L-type calcium-channel activity by thapsigargin and 2,5-t
      butylhydroquinone, but not by cyclopiazonic acid.
AB  - Thapsigargin (TG), 2,5-t-butylhydroquinone (tBHQ) and cyclopiazonic acid (CPA)
      all inhibit the initial Ca(2+)-response to thyrotropin-releasing hormone (TRH) by
      depleting intracellular Ca2+ pools sensitive to inositol 1,4,5-trisphosphate
      (IP3). Treatment of GH3 pituitary cells for 30 min with 5 nM TG, 500 nM tBHQ or
      50 nM CPA completely eliminated the TRH-induced spike in intracellular free Ca2+
      ([Ca2+]i). Higher concentrations of TG and tBHQ, but not CPA, were also found to
      inhibit strongly the activity of L-type calcium channels, as measured by the
      increase in [Ca2+]i or 45Ca2+ influx stimulated by depolarization. TG and tBHQ
      blocked high-K(+)-stimulated 45Ca2+ uptake, with IC50 values of 10 and 1 microM
      respectively. Maximal inhibition of L-channel activity was achieved 15-30 min
      after drug addition. Inhibition by tBHQ was reversible, whereas inhibition by TG
      was not. TG and CPA did not affect spontaneous [Ca2+]i oscillations when tested
      at concentrations adequate to deplete the IP3-sensitive Ca2+ pool. However, 20
      microM TG and 10 microM tBHQ blocked [Ca2+]i oscillations completely. The effect
      of drugs on calcium currents was measured directly by using the patch-clamp
      technique. When added to the external bath, 10 microM CPA caused a sustained
      increase in the calcium-channel current amplitude over 8 min, 10 microM tBHQ
      caused a progressive inhibition, and 10 microM TG caused an enhancement followed
      by a sustained block of the calcium current over 8 min. In summary, CPA depletes
      IP3-sensitive Ca2+ stores and does not inhibit voltage-operated calcium channels.
      At sufficiently low concentrations, TG depletes IP3-sensitive stores without
      inhibiting L-channel activity, but, for tBHQ, inhibition of calcium channels
      occurs at concentrations close to those needed to block agonist mobilization of
      intracellular Ca2+.

PMID- 7520694
TI  - On the interactions of Ca2+ and cyclosporin A with a mitochondrial inner membrane
      pore: a study using cobaltammine complex inhibitors of the Ca2+ uniporter.
AB  - The mitochondrial inner membrane contains a Ca(2+)-activated pore of possible
      relevance to the pathogenesis of ischaemia/reperfusion injury which is inhibited
      by the immunosuppressant cyclosporin A (CSA). The present study employs a number
      of novel cobaltammine complex inhibitors of the Ca2+ uniporter (mediating Ca2+
      uptake) to examine whether intramitochondrial Ca2+ influences the capacity of CSA
      to block the pore. Using dissipation of the inner membrane potential as a means
      of monitoring the state of the pore, it is shown that CSA blockade is facilitated
      as Ca2+ uptake is restricted. Ca2+ also depresses and reverses the binding of
      [3H]CSA to mitochondria, but Ca2+ is ineffective when its uptake is prevented. It
      is concluded that a high intramitochondrial Ca2+ concentration antagonizes pore
      inhibition by CSA. The significance of this is discussed.

PMID- 7520695
TI  - Interaction between glycine decarboxylase, serine hydroxymethyltransferase and
      tetrahydrofolate polyglutamates in pea leaf mitochondria.
AB  - The aim of the present work was to further determine how the T-protein of the
      glycine-cleavage system and serine hydroxy-methyltransferase (SHMT), two folate
      dependent enzymes from pea leaf mitochondria, interact through a common pool of
      tetrahydrofolate polyglutamates (H4PteGlun). It was observed that the binding
      affinity of tetrahydrofolate polyglutamates for these proteins continuously
      increased with increasing number of glutamates up to six residues. It was also
      established that, once bound to the proteins, tetrahydrofolate, a very O2
      sensitive molecule, was protected from oxidative degradation. The dissociation
      constants (Kd) of H4PteGlu5, the most predominant form of polyglutamate in the
      mitochondria, were approximately 0.5 microM for both T-protein and SHMT, whereas
      the Kd values of CH2-H4PteGlu5 were higher, 2.7 and 7 microM respectively. In a
      matrix extract from pea leaf mitochondria, the maximal activity of the glycine
      cleavage system was about 2.5 times higher than the maximal activity of SHMT.
      This resulted in a permanent disequilibrium of the SHMT-catalysed reaction which
      was therefore driven toward the production of serine and H4PteGlun, the
      thermodynamically unfavourable direction. Indeed, measurements of the steady
      state ratio of CH2-H4PteGlun/H4PteGlun (n = 1 or n = 5) during the course of
      glycine oxidation demonstrated that the methylene form accounted for 65-80% of
      the folate pool. This indicates that, in our in vitro experiments, CH2-H4PteGlun
      with long polyglutamate chains accumulated in the bulk medium. This observation
      suggests that, in these in vitro experiments at least, there was no channelling
      of CH2-H4PteGlu5 between the T-protein and SHMT.

PMID- 7520696
TI  - Roles of peptidyl-prolyl cis-trans isomerase and calcineurin in the mechanisms of
      antimalarial action of cyclosporin A, FK506, and rapamycin.
AB  - The immunosuppressive peptide cyclosporin A inhibits the growth of malaria
      parasites in vitro and in vivo, but little is known about its mechanism of
      antimalarial action. The immunosuppressive action of cyclosporin A is believed to
      result from binding of the drug to cyclophilins (intracellular peptidyl-prolyl
      cis-trans isomerases), and inhibition of the protein phosphatase calcineurin by
      the cyclosporin A-cyclophilin complex. Two immunosuppressive macrolides, FK506
      and rapamycin, bind to a distinct isomerase, FKBP12, and the FK506-FKBP complex
      also inhibits calcineurin. Calcineurin itself is apparently involved in signal
      transduction between the T-cell membrane and nucleus, and its inhibition blocks T
      cell activation. Rapamycin inhibits a later step in T-cell proliferation.
      Peptidyl-propyl cis-trans isomerase activity was detected in extracts of
      Plasmodium falciparum. It was completely inhibited by concentrations of
      cyclosporin A above 0.1 microM, but not by FK506 or rapamycin, and probably
      represented one or more cyclophilins. Comparison of the antimalarial and anti
      isomerase activities of a series of cyclosporin analogues failed to reveal a
      correlation between the two properties. Cyclosporin A and its more active 8'
      oxymethyl-dihydro-derivative, in combination with the cyclophilin-containing P.
      falciparum extract, inhibited the protein phosphatase activity of bovine
      calcineurin. Therefore inhibition of a putative P. falciparum calcineurin by a
      complex of CsA and cyclophilin might be responsible for the antimalarial action
      of the drug. The most active cyclosporin, however, was a 3'-keto-derivative of
      cyclosporin D (SDZ PSC-833) which inhibited P. falciparum growth with a 50%
      inhibitory concentration (IC50) of 0.032 microM (compared with 0.30 microM for
      cyclosporin A), but was a poor inhibitor of the parasite isomerase. 3'-Keto
      cyclosporin D has negligible immunosuppressive activity, but it strongly inhibits
      the P-glycoprotein of multi-drug resistant mammalian tumour cells. FK506 and
      rapamycin were also active antimalarials (IC50 of 1.9 and 2.6 microM,
      respectively) but in the absence of detectable FKBP in P. falciparum extracts,
      their mechanisms of antimalarial action remain unclear.

PMID- 7520697
TI  - DNA strand breakage in isolated nuclei subjected to bleomycin or hydrogen
      peroxide.
AB  - The sources of iron (Fe) and reductant required for DNA strand breakage by the
      antitumor drug bleomycin (Blm), H2O2 and ascorbate were investigated using nuclei
      instead of whole cells in order to study a simpler, related system that was
      subject to better control and easier chemical manipulation. Ehrlich ascites tumor
      cells were isolated and treated directly on filters, and analysed for DNA damage
      by alkaline and nondenaturing elution. Extraction and treatment buffers were
      depleted of trace Fe by passage through Mg(OH)2 gel. Nuclei were treated for 1 hr
      at 37 degrees. High levels of single- and double-strand breakage were obtained
      using Fe(III)Blm in the range 0.01 to 0.08 microM. In contrast, Blm was effective
      only at two orders of magnitude greater concentration. Cu(II)Blm was totally
      ineffective in causing damage. Depletion of nuclear protein thiols with N
      ethylmaleimide reduced double-strand breakage at the upper end of the FeBlm
      concentration-response curve. A 1 mM concentration of NADPH or NADH greatly
      increased the extent of double-strand breakage by 0.01 microM FeBlm, suggesting
      roles for cytochrome P450 or cytochrome b5 reductase in strand breakage.
      Fe(III)ATP (1:20 metal to ligand and 50 microM in Fe) and Fe(III)EDTA (1:2 metal
      to ligand and 50 microM in Fe) did not cause single-strand breaks. In the absence
      of added Fe, H2O2 or ascorbic acid (50 microM) caused less than one Gy-equivalent
      single-strand breakage. Addition of ascorbate plus Fe(III)ATP or Fe(III)EDTA
      produced breakage beyond the capacity of alkaline elution to analyse (5-6 Gy).
      Overall, the results indicate that Fe, which may contribute to DNA damage by Blm
      and forms of activated oxygen within cells, is not strongly bound in the nucleus
      and that nuclear thiols other than glutathione contribute reducing equivalents to
      Fe(III)Blm for the DNA damaging chemistry.

PMID- 7520698
TI  - Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE)
      and related compounds.
AB  - The inhibition of HIV-1 integrase by flavones and related compounds was
      investigated biochemically and by means of structure-activity relationships.
      Purified enzyme and synthetic oligonucleotides were used to assay for three
      reactions catalysed by integrase: (1) processing of 3' termini by cleavage of the
      terminal dinucleotide; (2) strand transfer, which models the integration step;
      and (3) "disintegration," which models the reversal of the strand transfer
      reaction. Inhibitions of all three reactions by flavones generally occurred in
      parallel, but caffeic acid phenethyl ester (CAPE) appeared to inhibit reaction 2
      selectively. CAPE, however, inhibited reactions 1 and 3 effectively when
      preincubated with the enzyme, suggesting that this compound differs from the
      flavones primarily in requiring more time to block the enzyme. The core integrase
      fragment consisting of amino acids 50-212 retained the ability to catalyse
      reaction 3, and flavones and CAPE retained the ability to inhibit. Hence, the
      putative zinc-finger region that is deleted in this fragment is probably not the
      target of inhibition. Inhibition by flavones usually required the presence of at
      least one ortho pair of phenolic hydroxyl groups and at least one or two
      additional hydroxyl groups. Potency was enhanced by the presence of additional
      hydroxyl groups, especially when present in ortho pairs or in adjacent groups of
      three. Inhibitory activity was reduced or eliminated by methoxy or glycosidic
      substitutions or by saturation of the 2,3 double bond. These structure-activity
      findings for flavones were generally concordant with those previously reported
      for reverse transcriptase and topoisomerase II. These findings are discussed in
      the context of a review of the effects of flavones on various enzymes, the
      possible mechanisms of inhibition, and the potential for building upon a general
      pharmacophore to generate target specificity.

PMID- 7520699
TI  - CSF findings in adrenoleukodystrophy: correlation between measures of cytokines,
      IgG production, and disease severity.
AB  - The childhood-onset cerebral form of adrenoleukodystrophy has a devastating
      neurologic prognosis. Unfortunately, there is no early method of distinguishing
      it from the more benign forms of adrenoleukodystrophy, such as
      adrenomyeloneuropathy. To evaluate the manner in which this disease entity may be
      reflected in the cerebrospinal fluid, we studied a consecutive series of 19
      patients, all with biochemically proved adrenoleukodystrophy. total protein,
      immunoglobulin production, cytokine levels, and cerebrospinal fluid pressure were
      measured. In this single sample of cerebrospinal fluid, a significant correlation
      existed between clinical stage of the illness and cerebrospinal fluid myelin
      basic protein. No correlation existed with total protein, cytokines, or measures
      of immunoglobulin production.

PMID- 7520700
TI  - The pathogenesis of chronic lymphocytic leukemia: analysis of the antibody
      repertoire.
AB  - CD5+ B cells predominate early in ontogeny and have been associated with
      autoantibody production. In chronic lymphocytic leukemia (CLL), B lymphocytes
      express CD5 and frequently produce autoantibodies using developmentally regulated
      variable (V)-gene segments. Does the self-reactivity observed in CLL reflect
      transformation of a 'fetal' lineage of cells, or could overexpansion of these B
      cells occur as a consequence of antigen stimulation? Harry Schroeder and
      Guillermo Dighiero have reviewed the literature describing antibody sequences in
      CLL and have compared them with the 'fetal' repertoire. This analysis indicates
      that CLL cells use a repertoire characteristic of mature cells, and suggests that
      antigen may play a role in the pathogenesis of this disease.

PMID- 7520701
TI  - cDNA cloning of c33-c antigen gene derived from NS3 region of Chinese HCV genome,
      expression in Escherichia coli and development of HCV EIA second-generation
      diagnostic kit.
AB  - A cDNA fragment of about 860 bp corresponding to the c33-c gene in the non
      structural region 3 (NS3) of HCV genome was obtained from one plasma derived from
      a Chinese HCV carrier who came from Tai' an of Shandong Province, China by the
      application of reverse transcription (RT) and polymerase chain reaction (PCR)
      techniques. After the sequence of the cDNA fragment was determined and compared
      with the equivalent region of the HCV-I (HCV-US) and HCV-II (HCV-BK) genomes, the
      nucleotide/amino acid sequence homologies were found to be 79.2%/91.3%/ and
      91.3%/93.9%, respectively. The prokaryotic expression vector pBV220 was employed
      for the overproduction of c33-c native recombinant protein in E. coli cells. The
      expression products were detected by enzyme-linked immunosorbent assay (ELISA)
      and Western blotting with antisera of chronic hepatitis C patients, and a
      molecular weight 31 kD of c33-c viral protein was shown to account for 14% of the
      total cellular soluble proteins. This product was extracted from the bacterial
      lysate by lysozyme, Triton X-100 and urea treatment, and purified through ion
      exchange chromatography. The purified c33-c protein combined with a branch
      peptide MAP-C-19 representing immunodominant epitopes on the nucleocapsid region
      of HCV genome was used to develop a Chinese HCV EIA 2nd-generation diagnostic kit
      for the detection of anti-HCV antibodies. Its specificity, sensitivity and
      reproducibility were all in keeping with the indexes of the national standard for
      the quality control of the HCV diagnostic kit. The agreement rate between our kit
      and Abbott company's HCV EIA second-generation diagnostic kit was 99.33%, and the
      identified rate of positive anti-HCV of our kit was 2% more than that of the
      Abbott company's kit.

PMID- 7520702
TI  - Identification of a distal regulatory sequence of the human IGFBP-1 gene promoter
      and regulation by the progesterone receptor in a human endometrial adenocarcinoma
      cell line.
AB  - The activity of the insulin-like growth factor binding protein-1 (IGFBP-1) gene
      promoter was studied in the human endometrial adenocarcinoma cell line HEC-1B.
      Basal promoter activity was directed by the region +68 to -207 bp, similar to
      observations in the hepatoma HepG2 cell line. A distal regulatory sequence
      approximately -2.6 kb from the transcription initiation site strongly enhanced
      the activity of the IGFBP-1 gene promoter in HEC-1B cells, but not in HepG2
      cells. Sequence analysis revealed that this active region resides in 105 bp
      between -2,628 to -2,732 bp (the Rsa I-Cla I fragment). This region contains many
      putative active motifs homologous to known cis elements. Additional deletion and
      mutation in the Rsa I-Cla I fragment showed that the activity was confined to a
      58-bp DNA fragment. In cells treated with progestin and co-transfected with
      progesterone receptor vector hPR1, the CAT activity derived from constructs
      containing the Rsa I-Cla I fragment was reduced in a dose-dependent manner. The
      active DNA fragment also stimulated the activity of the heterologous TK/CAT
      promoter in HEC-1B cells, while the PR complex inhibited this activity by 50%.
      These observations indicate that most of the regulation of the IGFBP-1 gene in
      HEC-1B cells is derived from the distal promoter region confined to the Rsa I-Cla
      I fragment and that the same region mediates an inhibitory effect from the
      progesterone receptor.

PMID- 7520703
TI  - Primary sequence and functional analysis of the bovine galanin gene promoter in
      human neuroblastoma cells.
AB  - Galanin (GAL) is a biologically active neuropeptide that has been suggested to
      play a role in stress-induced inhibition of insulin secretion, in dementia of the
      Alzheimer's type, and in the regulation of growth hormone secretion. We report
      here the isolation of a bovine genomic clone containing more than 5-kb 5'
      flanking sequences. Partial sequence analysis of the genomic clone revealed an
      atypical TATA-box in the promoter (ATAAATA) and several consensus sequences that
      typically bind transcription factors, including those that bind NF kappa B, Sp1,
      and AP-2. Primer extension and RNase protection analyses revealed that
      transcription is initiated at two sites, 28 and 31 bp, respectively, downstream
      from the TATA-box. To locate functionally active regulatory elements on the GAL
      gene, we first identified a neural crest-derived human neuroblastoma cell line,
      SK-N-SH subclone SH-SY5Y, that expressed easily detectable levels of endogenous
      GAL mRNA. We then constructed plasmids containing various lengths of bovine GAL
      5'-flanking sequences and the first exon fused to a reporter plasmid encoding
      luciferase. Transfection of these plasmids into the SH-SY5Y cells and analysis by
      transient expression indicated that 131 bp of 5' gene sequence was sufficient to
      obtain maximal basal expression. Further, expression was suppressed 16-fold when
      5 kb were included, suggesting the presence of a distal repressor element(s). In
      another set of experiments, we found that GAL mRNA levels could be induced more
      than 10-fold by 20-hr treatment with phorbol 12-myristate 13-acetate (PMA). In
      cells transfected with the same plasmids, luciferase activity was also induced by
      PMA, but the degree of induction did not significantly differ among the deletion
      constructions (varying from six- to eight-fold), suggesting that elements
      conferring PMA induction and/or RNA stabilization may be located within 131 bp of
      the transcriptional start site, in the first exon, or on gene sequences not
      studied here.

PMID- 7520705
TI  - Extrafollicular reticulum cells in pathologic lymph nodes.
AB  - Extrafollicular reticulum cells in lymph nodes are heterogeneous. They express
      cytokeratins, desmin, and/or vimentin as their intermediate filament profile.
      Using those markers, we undertook an immunohistochemical study of human lymph
      nodes under various pathologic conditions. Samples included 15 simple reactive
      lymph nodes, 7 follicular hyperplasia, 1 necrotizing lymphadenitis, 4 tuberculous
      lymphadenitis, 13 malignant lymphoma (9 non-Hodgkin's and 4 Hodgkin's lymphomas),
      and 11 metastatic adenocarcinoma. In lymph nodes with follicular hyperplasia,
      cytokeratin and/or desmin expressing reticulum cells displayed a characteristic
      dendritic meshwork in the subcapsular, perisinusoidal, and paracortical regions.
      In other forms reactive lymph nodes, they were similarly distributed but were
      less prominent. By SDS-PAGE and immunoblotting, cytokeratin polypeptides were
      identified. In necrotizing lymphadenitis, they were increased and the pattern of
      distribution was disturbed. In tuberculous lymphadenitis, they were also
      increased and located at nongranulomatous as well as in perigranulomatous areas.
      In lymphomas the reticular meshwork was entirely obliterated. Cytokeratin or
      desmin expressing reticulum cells were rarely seen within tumors. The reticular
      meshwork was also obliterated in metastatic carcinoma. However, the meshwork was
      maintained in uninvolved areas. In conclusion, extrafollicular reticulum cells
      displayed characteristic patterns of distribution under various pathologic
      conditions, and may be implicated in the pathogenesis of those pathologic
      conditions in human lymph nodes.

PMID- 7520704
TI  - Thymic epithelial cells of severe combined immunodeficiency (SCID) mice.
AB  - To characterize thymic epithelial cells of SCID (severe combined
      immunodeficiency) mice in comparison with those of Balb C mice, we did an
      immunohistochemical study using cortical and medullary epithelial cell specific
      monoclonal antibodies (MoAbs), Th-3 and Th-4, as well as gel electrophoresis and
      immunoblotting. The thymi of SCID mice were composed of epithelial cells and a
      few lymphocytes. Most epithelial cells were immunostained diffusely with Th-3,
      which indicated that they might be "cortical-type" epithelial cells. There were a
      few clusters of stellate cells with dendritic processes which were negative with
      Th-3 but stained strongly with Th-4. Cortical type epithelial cells and most of
      the Th-4 reacting cells were strongly immunostained with cytokeratin antibody
      MNF116. By immunoblotting, cytokeratin polypeptides No. 10 and 18 were detected
      in both SCID and Balb C mice; however, the relative amounts of each cytokeratin
      polypeptides were different. With immunohistochemical and immunoblotting results,
      we conclude; 1) Th-3 and Th-4 are reliable markers for cortical and medullary
      thymic epithelial cells in SCID mice; 2) disorganization of cells thymic
      structure is mostly due to maldevelopment of medullary epithelial and T
      lymphocytes; and 3) the composition of cytokeratin subfamilies of SCID mice thymi
      may represent a phenotypic marker of the maldevelopment of medullary epithelial
      cells.

PMID- 7520706
TI  - A lysate ribonuclease protection assay.

PMID- 7520707
TI  - Acid secretion in alpha-toxin-permeabilized gastric glands.
AB  - Rabbit gastric glands were treated with alpha-toxin to test for permeabilization
      of basolateral membrane and retention of functional activity of parietal cells.
      Treatment with up to 400 U alpha-toxin/mL resulted in a dose-dependent increase
      in permeabilization, as judged by nuclear uptake of trypan blue (960 daltons),
      while causing relatively little loss of cytoplasmic macromolecules in the size
      range of lactate dehydrogenase (134,000 daltons). In the presence of cAMP and
      ATP, alpha-toxin-permeabilized resting gastric glands were stimulated to
      accumulate aminopyrine by approximately 10-fold over glands incubated without
      added nucleotides. Aminopyrine accumulation in stimulated permeabilized glands
      was inhibited by specific H+,K(+)-ATPase inhibitors, omeprazole and SCH-28080,
      and by the selective inhibitor of protein kinase A, H-89 (IC50 = 7.17 +/- 2.05
      microM; n = 4). Aminopyrine accumulation in the alpha-toxin-treated glands was
      dependent on both exogenous ATP and cAMP; however, when no exogenous ATP was
      present, cAMP-activated aminopyrine accumulation reached approximately 50% of
      maximum, and at levels of ATP > 0.05 mM, maximal aminopyrine accumulation
      occurred without exogenous cAMP. In the presence of ATP alone, aminopyrine
      accumulation in permeabilized glands achieved 61.1 +/- 3.2% (n = 10; range, 50
      70%) of the values measured on paired samples of intact glands stimulated with
      histamine plus isobutylmethylxanthine. These results demonstrate the functional
      responsiveness of alpha-toxin-permeabilized resting gastric glands. The
      participation of a protein kinase A dependent pathway during activation of
      permeabilized parietal cell is proposed.

PMID- 7520708
TI  - Regulation of adhesion-related protein tyrosine kinases during in vitro
      differentiation of retinal pigment epithelial cells: translocation of pp60c-src
      to the nucleus is accompanied by downregulation of pp125FAK.
AB  - In the present report we show that induction of expression of a differentiated
      phenotype in cultured retinal pigmented epithelium of chick embryo is accompanied
      by coordinate regulation of expression and distribution of two adhesion-related
      nonreceptor protein tyrosine kinases, pp60c-src and pp125FAK. pp60c-src
      translocates from the cell surface in flat undifferentiated cells to the nucleus
      in the packed differentiated cells. In contrast, pp125FAK, abundant in focal
      adhesions of flat undifferentiated cells, is downregulated in cells that have
      differentiated and packed into an epithelial sheet.

PMID- 7520709
TI  - Antigen-specific suppression of antibody responses by T lymphocytes cytotoxic for
      antigen-presenting cells.
AB  - In this study we demonstrated an alternative model of the antigen (Ag)-specific
      suppression of antibody response in mice. Splenocytes that were taken from BALB/c
      mice immunized by i.v. injection of soluble human serum albumin (HSA) or
      ovalbumin exhibited MHC-restricted Ag-specific cytotoxicity for the respective
      antigen-presenting cells (APC). When HSA-primed splenocytes cultured with Ag and
      interleukin-2 (IL-2) were treated with anti-CD4 or anti-CD8 monoclonal antibody
      (mAb) plus complement, CD8+ and CD4+ T cells exhibited nearly the same level of
      cytotoxicity against APC. Furthermore, HSA-primed CD4+ and CD8+ T cells released
      the same amount of interferon-gamma (IFN-gamma) when stimulated with Ag and IL-2.
      Recombinant IFN-gamma was shown to suppress the in vitro plaque-forming cell
      (PFC) response to sheep red blood cells (SRBC) only when it was added within 24 h
      after addition of Ag. The supernatants from both HSA-primed CD4+ and CD8+ T cells
      suppressed the PFC response to SRBC in vitro, and the suppressive activity was
      abrogated by anti-IFN-gamma mAb, but increased by anti-IL 4 mAb. These results
      suggest that in our system the effector cells for Ag-specific suppression of the
      antibody response in mice are both the cytotoxic type 1 clones (IFN-gamma
      producing) of CD4+ and CD8+ T cells for APC, and that IFN-gamma is a major
      extracellular effector molecule for such suppression.

PMID- 7520710
TI  - Flow cytometric measurement of the production of reactive oxygen intermediate in
      activated rat mast cells.
AB  - The production of reactive oxygen intermediates (ROI) in compound 48/80- or
      calcium ionophore A 23187- activated pleural or peritoneal mast cells was
      monitored using flow cytometry and the fluorescence indicator dihydrorhodamine
      123 (a derivate of rhodamine 123). Mast cell degranulation and ROI production
      were estimated by flow cytometric fluorescence and light-scatter analysis. In
      addition, activation was monitored by spectrofluorimetric measurement of
      histamine secretion from the cells. We used flow cytometric measurement of narrow
      and wide angle scatter and fluorescence intensity to distinguish between
      degranulated and resting mast cells during activation and to monitor the two
      populations separately. Both stimuli induced a dose-dependent elevation of ROI
      production in mast cells which was accompanied by cell degranulation and
      histamine secretion. These alterations were completely abolished by preincubation
      of the mast cells with diethyldithiocarbamate (DTC). Using low concentrations of
      DTC partial decrease of degranulation and histamine secretion was observed while
      ROI production was blocked. D-mannitol increased ROI production in stimulated
      mast cells without a marked effect on degranulation or histamine secretion. The
      data suggest that mast cell degranulation (histamine secretion) and ROI
      production are independent processes.

PMID- 7520711
TI  - Detection of anti-HCV antibodies in immunoglobulin preparations by recombinant
      immunoblot assay.
AB  - The presence of anti-HCV antibodies in immunoglobulin preparations was
      investigated by recombinant immunoblot assay (RIBA) and enzyme immunoassay (EIA).
      While EIA was found to be suitable for detecting anti-HCV antibodies in
      immunoglobulin preparations, the RIBA could not be used without modifying the
      standard procedure developed for use with human sera. The two modifications were:
      (1) incubation with the anti-human IgG conjugate in a single test tube for each
      strip, instead of in a common vessel; (2) removal of the conjugate after 15 min
      and its replacement with fresh conjugate for a second 15 min incubation period.
      Thirty-six immunoglobulin preparations were tested using this modified procedure.
      Twenty-nine out of 31 (93.5%) preparations received in 1992 were anti-HCV
      positive, whereas the five immunoglobulin preparations received in 1993 were
      negative. These results were compared with those obtained on the same samples
      with the EIA. The percentage of samples positive with EIA was 74.2%. The
      difference between the results obtained with modified RIBA and EIA was
      statistically significant (P < 0.05).

PMID- 7520712
TI  - Rapid simultaneous screening for DNA integrity and antigen specificity of clones
      selected by phage display.

PMID- 7520713
TI  - Difference in biological effects between insulin-like growth factor binding
      protein 1 and 3.
AB  - Insulin-like growth factor binding proteins 1 and 3 are essentially known as
      regulators of IGF bioactivity. However, we previously showed that IGFBP-3 was
      able, in chick embryo fibroblast (CEF), to 100% inhibit DNA synthesis stimulated
      by calf serum, while the maximal inhibition found with IGFBP-1 was 60%,
      suggesting a difference between the two IGFBPs in their biological functions.
      Results of the present work agree with this assumption: (a) Recombinant human
      IGFBP-3, like rat IGFBP-3, was able to 100% inhibit DNA synthesis stimulation
      induced by human serum, while this stimulation was 75% decreased by IGFBP-1.
      However, the most striking difference was observed when the effects of the two
      IGFBPs were compared for stimulation induced by a serum growth factor (SGF)
      fraction depleted in IGFs. Stimulation induced by the SFG fraction was more
      significantly decreased (p < 0.001) by IGFBP-3 than by IGFBP-1. The mean percent
      inhibition +/- SEM was 67.1 +/- 2.5 in the presence of IGFBP-3 (200 ng/ml) and
      29.3 +/- 2.7 and 34.2 +/- 4 in the presence of 200 and 400 ng/ml IGFBP-1
      respectively. Inhibition by 200 ng/ml IGFBP-1 and inhibition by 6 ng/ml IGFBP-3
      were additive. However, inhibition by IGFBP-3 and that by IGFBP-1 were no longer
      additive at high concentrations of IGFBP-3, which might thus replace IGFBP-1. (b)
      FGF stimulation of CEF was similarly inhibition (65% and 70%) by IGFBP-1 and
      IGFBP-3. (c) TGF beta stimulation of CEF was more strongly decreased by IGFBP-3
      (90%) than by IGFB-1 (60%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520715
TI  - Characterization of CD34+HLA-DR-CD38+ and CD34+HLA-DR-CD38- progenitor cells from
      human umbilical cord blood.
AB  - In this study we show that depletion of cells expressing mature cell markers,
      including HLA-DR, followed by positive cell sorting for cells expressing CD34 and
      CD38, can be used to define functionally distinct hematopoietic cells from human
      umbilical cord blood (HUCB). The CD34+HLA-DR-CD38+ population contained the
      majority of directly clonogenic cells, while the optimal ability to maintain long
      term co-culture with bone marrow stromal cells was present within the CD34+HLA-DR
      CD38- population. 1.2 +/- 0.4% of the CD34+HLA-DR-CD38- cells plated at 1
      cell/well and grown in the presence of hematopoietic growth factors (HGF) formed
      hemopoietic colonies. Mesenchymal elements were observed in 20% of these
      cultures. No cell growth, however, was observed when the CD34+HLA-DR-CD38- cells
      were cultured in the absence of HGF. This is in contrast with the findings in
      fetal bone marrow which demonstrated the presence of stem cells that were
      independent of HGF. Thus, while it is possible to isolate very immature
      hemopoietic progenitor cells from HUCB defined by the phenotype Lin-CD34+HLA-DR
      CD38-, these cells do not appear to exhibit the pluripotentiality of the
      analogous population reported in fetal bone marrow. We conclude that these cells
      are absent or at a very small frequency in HUCB.

PMID- 7520714
TI  - Expression of protein tyrosine kinases in islet cells: possible role of the Flk-1
      receptor for beta-cell maturation from duct cells.
AB  - To elucidate the expression of genes of importance for beta-cell replication and
      the production of insulin, single-stranded cDNAs from different preparations of
      insulin producing cells were used as template for the polymerase chain reaction
      (PCR) using primers specific for protein tyrosine kinases (PTKs). In RINm5F
      cells, as well as in fetal rat islets, the receptor PTK fetal liver kinase-1 (Flk
      1) was expressed among other receptor and cytoplasmic tyrosine kinases. To
      elucidate the putative effects of stimulation of the Flk-1 receptor, fetal rat
      islet-like structures were cultured in the presence of the ligand for this
      receptor, vascular endothelial growth factor (VEGF). VEGF was found to stimulate
      both the insulin content/islet DNA ratio and the accumulation of insulin in the
      culture medium without affecting the rates of beta-cell replication. To
      investigate the localization of expression of the Flk-1 receptor in the pancreas,
      serial sections of fetal pancreata were immunostained for Flk-1 and insulin.
      Expression of Flk-1 was detected in endothelial-like cells and cells lining
      pancreatic ducts. The latter are considered to contain precursor cells for the
      endocrine pancreas. In conclusion, specific protein tyrosine kinases are
      expressed in islet cells, and are presumably participating in the regulation of
      islet function. Specifically, the receptor PTK Flk-1 may play a role of beta-cell
      maturation from pancreatic duct cells.

PMID- 7520716
TI  - Expression of granulocyte colony-stimulating factor and its receptor at the
      fetomaternal interface in murine and human pregnancy.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a cytokine which regulates
      proliferation and differentiation of neutrophilic granulocytes, and its receptor
      (G-CSF-R) is a member of the hemopoietic growth factor receptor family. We
      studied the expression of G-CSF and G-CSF-R at the fetomaternal interface in
      murine and human pregnancy. Immunohistochemical analysis and in situ
      hybridization indicated that both G-CSF and G-CSF-R are expressed in mouse
      spongiotrophoblasts and placental labyrinths, and human placental
      cytotrophoblasts and syncytiotrophoblasts. They were also detected in mouse
      decidual basalis cells and endometrial epithelial cells, and human decidual
      stromal cells and endometrial gland cells. These results suggest that G-CSF plays
      a role in decidual and placental functions by autocrine and paracrine mechanisms.

PMID- 7520717
TI  - Mitogenic and in vitro angiogenic activity of human recombinant heparin affin
      regulatory peptide.
AB  - We have previously described the purification of a heparin binding growth factor
      from adult bovine brain named heparin affin regulatory peptide (HARP), which was
      identical to an uterus derived growth factor named pleiotrophin and to a
      developmentally regulated neurite promoting factor named heparin-binding growth
      associated molecule. However, for yet unclear reasons, the mitogenic activity of
      this purified polypeptide following isolation from animal tissue extracts is a
      subject of controversy, due to conflicting and irreproducible data when produced
      by recombinant DNA technologies in E. coli or insect cells. The purified protein
      was inactive in mitogenic assays but the natural molecule was active in assay of
      neurite outgrowth. In order to clarify these conflicting results and to obtain a
      recombinant protein free from other contaminating heparin-binding growth factors,
      we have cloned human cDNA encoding human HARP, engineered its expression in NIH
      3T3 cells and characterised the resulting recombinant polypeptide. Purified
      recombinant HARP displayed mitogenic activity for capillary endothelial cells
      with half-maximal stimulation at approximately 1 ng/ml (55 pM) and induced
      angiogenesis in an in vitro model. Interestingly, while the NH2 terminal sequence
      of tissue purified HARP was NH2-GKKEKPEKK, the NH2 terminal sequence of the
      biologically active recombinant protein was NH2-AEAGKKEKPEKK, corresponding to a
      three amino acid extended form.

PMID- 7520718
TI  - Locations and chemistries of sympathetic nerve cells that project to the
      gastrointestinal tract and spleen.
AB  - Retrograde tracing was used to determine the locations of sympathetic nerve cells
      whose axons project to the stomach, small intestine, caecum, proximal colon,
      distal colon and spleen of the guinea-pig. Projections from prevertebral ganglia
      were organotopically arranged within and between ganglia. The cranially located
      coeliac ganglion provided the major input to proximal gut regions; the distal gut
      received more caudal input, from superior and inferior mesenteric and the
      hypogastric nerve ganglia. Nevertheless, minor proportions of the innervation of
      some target organs arose from other than the closest ganglion and the caecum had
      input from each of the coeliac, superior mesenteric and inferior mesenteric
      ganglia. Topography within a ganglion was best defined in the coeliac, in which
      nerve cells whose axons projected to the spleen, stomach and duodenum were
      preferentially laterally located, whereas most of those projecting to the
      proximal colon were medial. Fewer neurons projected from paravertebral--compared
      with prevertebral--ganglia to abdominal viscera. Projections to the stomach came
      from all thoracic chain ganglia, those to the duodenum and spleen from lower
      thoracic ganglia and those to the large intestine from lumbar chain ganglia. It
      is suggested that the previously reported chemical topography of nerve cells in
      sympathetic ganglia might be secondary to their organotopic organization.

PMID- 7520719
TI  - Cytokeratin expression during regeneration of the intralobular duct in rat
      submandibular glands after YAG laser irradiation.
AB  - Changes in the expression of cytokeratin subunits during regeneration of the
      intralobular duct in partially injured rat submandibular glands were
      investigated. Limited parts of rat submandibular glands were injured by
      irradiation with YAG laser. Irradiated glands were investigated histologically
      and immunohistochemically using anti-cytokeratin monoclonal antibodies, RCK105
      and CK19. Irradiated areas became necrotic one day after YAG laser irradiation.
      At three and five days, duct-like structures and epithelial clusters began to
      regenerate at the periphery of the remaining lobule. Epithelial clusters without
      ductal spaces were situated at the terminal portion of the duct-like structures.
      At seven and ten days, duct-like structures were composed of cuboidal or low
      columnar cells, and the number of epithelial clusters decreased.
      Immunohistochemically, cells of intralobular ducts in normal rat submandibular
      glands reacted to RCK105 and CK19. At three and five days, the epithelial cells
      of duct-like structures were positive for both antibodies. Many cells in the
      epithelial clusters showed negative reaction. However, in some epithelial
      clusters, inner cells and cells facing narrow luminal spaces were positive for
      both antibodies. At seven and ten days, positive reaction for both antibodies was
      identified in duct-like structures. This study showed that cells of the
      epithelial cluster were less mature than those of the duct-like structure, and
      that in the epithelial cluster, the inner cells were the first to differentiate
      into intralobular ductal cells.

PMID- 7520720
TI  - Distribution of substance P-containing and catecholaminergic nerve fibers in the
      rabbit carotid body: an immunohistochemical study in combination with
      catecholamine fluorescent histochemistry.
AB  - The distribution of substance P (SP)-immunoreactive nerve fibers in the rabbit
      carotid body was studied in combination with catecholamine autofluorescence
      images of sections where SP immunoreactivity was confirmed. Immunoreactivity for
      SP was found in nerve fibers distributed in the parenchyma of the carotid body.
      No glomus cells with SP immunoreactivity were observed in the carotid body. On
      comparing the distribution of SP-immunoreactive fibers with the catecholamine
      autofluorescence image in a single section, most SP fibers appeared associated
      with the fluorescent glomus cells, and were located around clusters of them.
      These results support the suggestion that SP fibers in the cat and rat carotid
      bodies are involved in chemosensory mechanisms. Furthermore, a survey of the
      present results and previous ones reported by other workers indicates that SP may
      be an essential neuropeptide in chemoreceptor organs in most vertebrates from
      amphibians on upwards evolutionally. In addition, the courses of some
      catecholaminergic fibers precisely agreed with those of some SP fibers. This
      suggests that certain sympathetic nerve fibers also contain SP.

PMID- 7520721
TI  - Generation of human monoclonal antibodies against HIV-1 proteins; electrofusion
      and Epstein-Barr virus transformation for peripheral blood lymphocyte
      immortalization.
AB  - Electrofusion and EBV transformation were studied by immortalizing human PBLs
      from blood of HIV-1-positive volunteers. A panel of 33 cell lines producing human
      monoclonal antibodies (Hu-MAbs) against HIV-1 was established by cell fusion or
      EBV transformation. For the first fusion experiments the source of B lymphocytes
      was peripheral blood of HIV-1-infected donors in CDC stages II or III with CD4
      cell counts higher than 500/mm3. Later on, from these patients only, those with
      high anti-HIV titers were chosen as blood donors. By that means the yield of
      stable specific hybridomas was increased twofold. In our experiments
      electrofusion turned out to be a more efficient immortalization method than EBV
      transformation, due to a high and constant immortalization rate. The hybridomas
      were stable after intensive subcloning and could be cultivated over a period of 8
      months without loss in monoclonal antibody production. Immunoglobulin class,
      subtype, reactivity against HIV-1 proteins, Western blot patterns,
      immunofluorescence, and epitopes were characterized. The subtype of all
      antibodies was IgG1 or IgG3. The light chain was predominantly kappa. All
      antibodies showed reactivity against HIV-1 envelope or core protein. All
      hybridomas were stable and suited for mass production. Several Hu-MAbs are
      becoming an important tool in the field of diagnosis, research, and
      immunotherapy.

PMID- 7520722
TI  - Cell line-dependent release of HIV-like gag particles after infection of
      mammalian cells with recombinant vaccinia viruses.
AB  - We investigated the production of Gag particles by Vero, CV-1, or 1D cells
      infected with different vaccinia virus recombinants expressing HIV gag or gag-pol
      genes. Immunoblots of (centrifuged) culture media from 1D cells infected with
      vMM5, a vaccinia virus recombinant expressing the HIV-2 gag-pol genes, revealed
      the presence of abundant particles that contained (mostly processed) Gag
      antigens. In contrast, Gag particles were found only in low amounts in the
      culture medium from Vero cells infected with the same HIV gag-pol vaccinia virus
      recombinant; the Gag precursor remained associated with the infected Vero cells
      and was efficiently processed. This low excretion of Gag particles after
      infection of Vero cells with vMM5 was also demonstrated by assays of reverse
      transcriptase activity in the pellet of centrifuged culture medium. Cell
      fractionation showed that Gag proteins were predominantly found in the membrane
      fraction from both 1D and Vero cells. Electron microscopy observations of 1D or
      of Vero cells infected with vMM5 vaccinia virus recombinant revealed in both
      cases the presence of particles budding at the plasma membrane. However, the
      shape of the budding particles was different in the two cell lines, with immature
      forms present in the membrane from the infected Vero cells. An inefficient
      excretion of Gag particles was also observed after infection of Vero cells with
      different vaccinia virus recombinants expressing either an uncleaved HIV-2 Gag
      protein or the HIV-1 gag-pol genes, as judged both by immunoblot and reverse
      transcriptase activity assays.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520723
TI  - [The nonexcisional palliative surgical treatment of carcinoma of the thoracic
      esophagus and cardia].
AB  - OBJECTIVE: To review our experience with the palliative treatment for
      unresectable carcinoma of the esophagus over a 15 years period. The available
      methods, their indications and results are analyzed. EXPERIMENTAL DESIGN: A
      retrospective study where the palliative methods used, their indication, their
      complications and the survival of the patients have been analyzed. PATIENTS: A
      whole of 114 patients with unresectable carcinoma of the thoracic esophagus and
      esophagogastric junction, have been included. RESULTS: The most widely used
      palliative method was the Celestine tube and the main indication was the
      unresectable tumor. Mean survival was 4.6 months, and mean hospital stay was 10
      days. CONCLUSIONS: The carcinoma of the esophagus is diagnosed too late. That's
      why, in most cases, it is unresectable. However, it is important to offer some
      palliative treatment to the patients to improve, if possible, their quality of
      life. We suggest that the requirements for a palliative method are the following:
      easy and quick technique, brief hospital stay, improvement of patient comfort and
      low morbimortality.

PMID- 7520724
TI  - Osteogenesis imperfecta: comparison of molecular defects with bone histological
      changes.
AB  - Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by a
      predisposition to bone fracturing, and usually resulting from mutations in the
      genes encoding type I collagen. This report describes the molecular defects in a
      patient with type II OI and another with type III OI. These patients were
      demonstrated to possess point mutations resulting in glycine-->arginine
      substitutions within the triple helical domain of the alpha 1(I) or alpha 2(I)
      collagen polypeptide chain. The defect in the type II OI patient affected residue
      211 of the alpha 1(I) triple helical domain, and constitutes the most amino
      terminal lethal glycine-->arginine substitution described to date. The
      substitution in the type III OI patient affected residue 427 of the alpha 2(I)
      triple helical domain. Both defects were informative in that they identified the
      regions of the alpha 1(I) and alpha 2(I) collagen chains in which the phenotypes
      associated with glycine-->arginine substitutions undergo a transition between
      lethal and nonlethal forms, thereby allowing a more reliable prognosis of disease
      severity. The histological examination of bone from these patients revealed
      striking abnormalities in the quantity and organization of mineralized bone
      structures, compared with age-matched controls. Although the patients were
      differently classified, no major differences in the magnitude of bone
      architectural changes could be perceived, consistent with the presence of their
      defects near a common phenotypic transition. The results are compatible with
      there being a gradient in severity between OI types II and III, and that
      parameters external to the gene mutations might account for the survival
      differences in the 2 cases presented in this study.

PMID- 7520725
TI  - Mast cell growth factor (C-kit ligand) in combination with granulocyte-macrophage
      colony-stimulating factor and interleukin-3: in vivo hemopoietic effects in
      irradiated mice compared to in vitro effects.
AB  - In the presence of hemopoietic cytokines such as granulocyte-macrophage colony
      stimulating factor (GM-CSF) and interleukin-3 (IL-3), mast cell growth factor
      (MGF; also known as steel factor, stem cell factor, and c-kit ligand) has proven
      to be a potent hemopoietic regulator in vitro. In these studies, we examined the
      in vivo effects of MGF in combination with GM-CSF or GM-CSF plus IL-3. Effects
      were based on the ability of these cytokines to stimulate recovery from radiation
      induced hemopoietic aplasia. Female B6D2F1 mice were exposed to a sublethal 7.75
      Gy dose of 60Co radiation followed by subcutaneous administration of either
      saline, recombinant murine (rm) MGF (100 micrograms/kg/day), rmGM-CSF (100
      micrograms/kg/day), rmIL-3 (100 micrograms/kg/day), or combinations of these
      cytokines on days 1-17 postirradiation. Recoveries of bone marrow and splenic
      spleen colony-forming units (CFU-s), granulocyte macrophage colony-forming cells
      (GM-CFC), and peripheral white blood cells (WBC), red blood cells (RBC) and
      platelets (PLT) were determined on days 14 and 17 during the postirradiation
      recovery period. MGF administered in combination with GM-CSF or in combination
      with GM-CSF plus IL-3 either produced no greater response than GM-CSF alone or
      down-regulated the GM-CSF-induced recovery. These results sharply contrasted
      results of in vitro studies evaluating the effects of these cytokines on
      induction of GM-CFC colony formation from bone marrow cells obtained from normal
      or irradiated B6D2F1 mice, in which MGF synergized with GM-CSF or GM-CSF plus IL
      3 to increase both GM-CFC colony numbers and colony size. These studies
      demonstrate a dichotomy between MGF-induced effects in vivo and in vitro and
      emphasize that caution should be taken in attempting to predict cytokine
      interactions in vivo in hemopoietically injured animals based on in vitro
      cytokine effects.

PMID- 7520726
TI  - The presence of a common antigen between human gastric cancer cells and OK-432.
AB  - Twenty two surgical specimens of gastric cancer resected after administration of
      OK-432 for the skin reaction test were examined to determine whether the cancer
      cells had the same antigens as OK-432, a product of hemolytic streptococcus
      cells. When the tissues were stained by the PAP method with anti-Su streptococcus
      antibody used as the primary antibodies, the common antigens were demonstrated in
      10 (45.5%) of the 22. The presence or absence of the common antigens was
      independent of the degree of skin reaction to OK-432, and the relations of the
      common antigens to other host responses were not clear in this study. This is the
      first report for the presence of such common antigens between human gastric
      cancer and OK-432.

PMID- 7520727
TI  - Enteropathic arthritis, Whipple's disease, juvenile spondyloarthropathy, and
      uveitis.
AB  - An association between inflammatory bowel disease and enteroarthritis and the
      spondyloarthropathies has been known of for a while. Within the past few years,
      ileocolonic studies have expanded the diagnostic accuracy of asymptomatic gut
      inflammation, and it now seems evident that chronic gut inflammation is either
      associated with or is even the cause of chronicity of peripheral arthritis and
      the development of ankylosing spondylitis. This situation, previously studied in
      adult patients, now appears also to affect pediatric patients with
      spondyloarthropathies, who seem to have similar genetic and inflammatory bowel
      findings. Chronic infection in the gut has been demonstrated in Whipple's
      disease. Analogously, infection or immunologic aberrations probably contribute to
      chronicity in other forms of spondyloarthropathy. Infection also might be
      involved, at least partly in attacks of uveitis, but activation of immunologic
      mechanisms can mediate tissue destruction during eye inflammation.

PMID- 7520728
TI  - Chlamydia trachomatis pneumonia in the severe combined immunodeficiency (SCID)
      mouse.
AB  - We have developed a model of pneumonia caused by the mouse pneumonitis agent
      (MoPn, murine Chlamydia trachomatis) in the C.B-17 severe combined
      immunodeficiency (SCID) mouse. In contrast to our prior models in the nude
      athymic (nu/nu) and heterozygous (nu/+) mouse, SCID mice lack B-cell function and
      gamma delta T-cell function. SCID mice were more susceptible to MoPn than nu/nu
      or nu/+ mice both by criteria of mortality and quantitative lung culture. SCID
      mice could be reconstituted with thymocytes to be more resistant to MoPn (in the
      absence of significant antibody production), but the protection was modest and
      less than that in T-cell reconstituted nu/nu mice in our previous studies. A nu/+
      MoPn-specific T-cell clone with a Th1-like cytokine profile also provided modest
      but significant protection without significant antibody production. The SCID
      mouse is a useful model to study T-cell-mediated immunity to MoPn in a B cell and
      gamma delta T-cell-deficient environment.

PMID- 7520729
TI  - The phloem-limited bacterium of greening disease of citrus is a member of the
      alpha subdivision of the Proteobacteria.
AB  - Using the PCR, we amplified the 16S ribosomal DNAs (rDNAs) of an Asian strain and
      an African strain of the uncultured, gram-negative, walled, phloem-limited
      bacterium-like organism (BLO) associated with citrus greening disease. We evaded
      coamplification of chloroplast 16S rDNA by using restriction enzymes; the
      chloroplast 16S rDNA was sensitive to BclI digestion and resistant to EcoRI
      digestion, while the 16S rDNA of the BLO was resistant to BclI digestion and
      sensitive to EcoRI digestion. The 16S rDNA of the African BLO strain was
      amplified from BclI-digested DNA extracted from infected periwinkle leaf midribs.
      The Asian strain was isolated from plant extract by using a specific monoclonal
      antibody coated onto the surface of a PCR tube. The 16S rDNAs of the two BLO
      strains were cloned and sequenced. Comparisons with sequences of 16S rDNAs
      obtained from the GenBank data base revealed that the two citrus greening disease
      BLOs belong to the alpha subdivision of the class Proteobacteria. Even though
      their closest relatives are members of the alpha-2 subgroup, these BLOs are
      distinct from this subgroup as we observed only 87.5% homology between the 16S
      rDNAs examined. Therefore, the two BLOs which we studied probably are members of
      a new lineage in the alpha subdivision of the Proteobacteria. We propose the
      trivial name "liberobacter" for this new group of bacteria and will wait until
      additional characteristics have been determined before we propose a formal name.

PMID- 7520730
TI  - Phylogenetic relationships between some members of the genera Neisseria,
      Acinetobacter, Moraxella, and Kingella based on partial 16S ribosomal DNA
      sequence analysis.
AB  - We obtained 16S ribosomal DNA (rDNA) sequence data for strains belonging to 11
      species of Proteobacteria, including the type strains of Kingella kingae,
      Neisseria lactamica, Neisseria meningitidis, Moraxella lacunata subsp. lacunata,
      [Neisseria] ovis, Moraxella catarrhalis, Moraxella osloensis, [Moraxella]
      phenylpyruvica, and Acinetobacter lwoffii, as well as strains of Neisseria
      subflava and Acinetobacter calcoaceticus. The data in a distance matrix
      constructed by comparing the sequences supported the proposal that the genera
      Acinetobacter and Moraxella and [N.] ovis should be excluded from the family
      Neisseriaceae. Our results are consistent with hybridization data which suggest
      that these excluded taxa should be part of a new family, the Moraxellaceae. The
      strains that we studied can be divided into the following five groups: (i) M.
      lacunata subsp. lacunata, [N.] ovis, and M. catarrhalis; (ii) M. osloensis; (iii)
      [M.] phenylpyruvica; (iv) A. calcoaceticus and A. lwoffii; and (v) N.
      meningitidis, N. subflava, N. lactamica, and K. kingae. We agree with the
      previous proposal that [N.] ovis should be renamed Moraxella ovis, as this
      organism is closely related to Moraxella species and not to Neisseria species.
      The generically misnamed taxon [M.] phenylpyruvica belongs to the proposed family
      Moraxellaceae, but it is sufficiently different to warrant exclusion from the
      genus Moraxella. Further work needs to be done to investigate genetically similar
      species, such as Psychrobacter immobilis, before the true generic position of
      this organism can be determined. Automated 16S rDNA sequencing with the PCR
      allows workers to accurately determine phylogenetic relationships between groups
      of organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520731
TI  - Photosynthetic symbionts of Aeschynomene spp. form a cluster with bradyrhizobia
      on the basis of fatty acid and rRNA analyses.
AB  - The relationship between photosynthetic rhizobia that nodulate 10 Aeschynomene
      species (Aeschynomene afraspera, Aeschynomene denticulata, Aeschynomene evenia,
      Aeschynomene indica, Aeschynomene nilotica, Aeschynomene pratensis, Aeschynomene
      rudis, Aeschynomene scabra, Aeschynomene schimperi, and Aeschynomene sensitiva)
      and reference strains of the genera Bradyrhizobium, Rhizobium, and Azorhizobium
      was investigated by analyzing cellular fatty acid methyl esters (FAME) and 16S
      rRNA sequences. The members of each genus produced very distinct FAME patterns,
      and the photosynthetic rhizobia formed a subcluster in the Bradyrhizobium
      cluster. The absence of the cyc C19:0 type of fatty acid in all of the
      photosynthetic rhizobium strains isolated from 10 Aeschynomene species
      distinguished these microorganisms from other known rhizobia, including strain
      BTAi 1, a photosynthetic symbiont of A. indica. We sequenced a 264-base segment
      of the 16S rRNA genes of selected strains after amplification by the PCR and
      compared the results with previously published sequences for species of rhizobia
      and related photosynthetic bacteria. Photosynthetic strains IRBG 2 (from A.
      afraspera), IRBG 230 (from A. nilotica), and ORS 322 (from A. afraspera) had
      identical sequences but were distinct from strain BTAi (from A. indica) and from
      strain IRBG 231 (from A. denticulata), which is similar to the type strain (DNA
      homology group Ia) of Bradyrhizobium japonicum. Nonphotosynthetic strain IRBG 274
      (from A. afraspera) was closely related to Bradyrhizobium elkanii (DNA homology
      group II). All of the photosynthetic rhizobia clearly fell into the
      Bradyrhizobium cluster. Although the results of the FAME and 16S rRNA analyses
      were in excellent agreement, our placement of the photosynthetic rhizobia is in
      apparent conflict with phenotypic data, as determined by numerical taxonomy
      (Ladha and So, Int. J. Syst. Bacteriol., in press) which placed the
      photosynthetic rhizobia in a coherent cluster that is as far from the genus
      Bradyrhizobium as the genera Rhizobium and Azorhizobium are. While the FAME and
      16S rRNA data probably provide a more reliable indication of phylogeny, the
      degree of phenotypic divergence observed raises questions concerning the
      polyphasic approach to bacterial systematics.

PMID- 7520732
TI  - Pseudomonas flavescens sp. nov., isolated from walnut blight cankers.
AB  - Two pseudomonad strains that produce a yellow cellular pigment, in addition to a
      diffusible fluorescent pigment on Kings medium B, were isolated from cankers on
      walnut trees. Biochemical properties, such as a positive oxidase reaction, a
      negative arginine dihydrolase reaction, and the production of a fluorescent
      pigment, in addition to the results of an extensive nutritional characterization
      study and DNA-DNA hybridization experiments, indicated that these strains belong
      to a new Pseudomonas rRNA group I species. This conclusion was supported by the
      results of a determination of the sequence of the PCR-amplified 16S rRNA gene and
      a comparison with the 16S rRNA genes of other bacterial species. The genomic DNAs
      of the strains had a base composition of 63 mol% G+C. The name Pseudomonas
      flavescens sp. nov. is proposed. Strain B62 (= NCPPB 3063) is the type strain of
      the species.

PMID- 7520733
TI  - Phylogenetic analysis and assessment of the genera Vibrio, Photobacterium,
      Aeromonas, and Plesiomonas deduced from small-subunit rRNA sequences.
AB  - We sequenced nearly complete small-subunit rRNAs of 54 reference strains
      belonging to the genera Vibrio, Photobacterium, Aeromonas, and Plesiomonas. We
      then performed a phylogenetic analysis by comparing the sequences which we
      obtained with all other known sequences for bacteria belonging to the gamma
      subgroup of the Proteobacteria (thus providing a data base consisting of 70
      sequences for the genera investigated), using methods such as neighbor joining,
      maximum likelihood, and maximum parsimony, as well as bootstrap, to assess the
      robustness of each topology. Our results confirmed that the family Vibrionaceae
      should include only Photobacterium and Vibrio species (but not Vibrio marinus);
      that Aeromonas species deserve family rank; and that Plesiomonas shigelloides is
      linked to the family Enterobacteriaceae. The genera Vibrio, Photobacterium,
      Aeromonas, and Plesiomonas, together with the family Enterobacteriaceae, the
      family Pasteurellaceae, and probably the genus Alteromonas, form a robust
      monophyletic unit within the gamma 3 subgroup of the Proteobacteria.

PMID- 7520734
TI  - Phylogenetic positions of novel aerobic, bacteriochlorophyll a-containing
      bacteria and description of Roseococcus thiosulfatophilus gen. nov., sp. nov.,
      Erythromicrobium ramosum gen. nov., sp. nov., and Erythrobacter litoralis sp.
      nov.
AB  - We analyzed the 16S ribosomal DNAs of three obligately aerobic,
      bacteriochlorophyll a-containing bacteria, "Roseococcus thiosulfatophilus,"
      "Erythromicrobium ramosum," and new isolate T4T (T = type strain), which was
      obtained from a marine cyanobacterial mat. "Roseococcus thiosulfatophilus" is a
      member of the alpha-1 subclass of the Proteobacteria and is moderately related to
      Rhodopila globiformis, Thiobacillus acidophilus, and Acidiphilium cryptum (level
      of sequence similarity, 90%). "Erythromicrobium ramosum" and isolate T4T are
      closely related to Erythrobacter longus and Porphyrobacter neustonensis (level of
      sequence similarity, 95%). These organisms are members of the alpha-4 subclass of
      the Proteobacteria. Strain T4T is a motile, red or orange bacterium. The major
      carotenoids are bacteriorubixanthinal and erythroxanthin sulfate. In vivo
      measurements revealed bacteriochlorophyll absorption maxima at 377, 590, 800, and
      868 nm. Strain T4T grows in the presence of 5 to 96/1000 salinity and uses
      glucose, fructose, acetate, pyruvate, glutamate, succinate, and lactate as
      substrates. On the basis of its distinct phylogenetic position and phenotypic
      characteristics which are different from those of Erythrobacter longus, we
      propose that strain T4T should be placed in a new species of the genus
      Erythrobacter, Erythrobacter litoralis. The descriptions of "Roseococcus
      thiosulfatophilus" and "Erythromicrobium ramosum" are emended.

PMID- 7520735
TI  - Phylogenetic classification of phytopathogenic mollicutes by sequence analysis of
      16S ribosomal DNA.
AB  - The phylogenetic relationships of 17 phytopathogenic mycoplasmalike organisms
      (MLOs) representing seven major taxonomic groups established on the basis of MLO
      16S ribosomal DNA (rDNA) restriction patterns were examined by performing a
      sequence analysis of the 16S rDNA gene. The sequence data showed that the MLOs
      which we examined are members of a relatively homogeneous group that evolved
      monophyletically from a common ancestor. In agreement with results obtained
      previously with other MLOs, our results also revealed that the organisms are more
      closely related to Acholeplasma laidlawii and other members of the anaeroplasma
      clade than to any other mollicutes. A phylogenetic tree based on 16S rDNAs showed
      that the MLOs which we examined can be divided into the following five primary
      clusters: (i) the aster yellows strain cluster; (ii) the apple proliferation
      strain cluster; (iii) the western-X disease strain cluster; (iv) the sugarcane
      white leaf strain cluster; and (v) the elm yellows strain cluster. The aster
      yellows, western-X disease, and elm yellows strain clusters were divided into two
      subgroups each. MLOs whose 16S rDNA sequences have been determined previously by
      other workers can be placed in one of the five groups. In addition to the overall
      division based on 16S rDNA sequence homology data, the primary clusters and
      subgroups could be further defined by a number of positions in the 16S rDNAs that
      exhibited characteristic compositions, especially in the variable regions of the
      gene.

PMID- 7520736
TI  - Identification of the Staphylococcus sciuri species group with EcoRI fragments
      containing rRNA sequences and description of Staphylococcus vitulus sp. nov.
AB  - Strains of a new species, Staphylococcus vitulus, were isolated from food and a
      variety of mammals. This species was recognized on the basis of the results of an
      analysis of genomic EcoRI fragments containing portions of the rRNA operons. The
      patterns of hybridized fragments obtained from strains belonging to the new taxon
      were sorted into a distinguishable cluster and were distinct from the
      Staphylococcus lentus and Staphylococcus sciuri patterns. The results of DNA-DNA
      hybridization reactions demonstrated that strains in this cluster were more
      closely related to S. lentus and S. sciuri than to other Staphylococcus species
      and yet were significantly different. While these strains had some of the
      phenotypic characteristics of the S. sciuri species group, the newly recognized
      taxon could be distinguished by its very small colonies on P agar, absence of
      alkaline phosphatase activity, and lack of acid production from L-arabinose,
      maltose, N-acetylglucosamine, D-mannose, and raffinose. The type strain of the
      new species is strain DD 756 (= ATCC 51145).

PMID- 7520737
TI  - Phenotypic and genotypic characterization of bradyrhizobia nodulating the
      leguminous tree Acacia albida.
AB  - Rhizobial isolates that were obtained from both surface and deep soil samples in
      the Sahelian and Sudano-Guinean areas of Senegal (West Africa) under Acacia
      albida trees were compared with representative strains of known rhizobial species
      and genera. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      of proteins was used to determine the taxonomic positions of these organisms and
      the relationships between isolates obtained from the surface and isolates
      obtained from deep soil. Most of the isolates belonged to eight electrophoretic
      clusters containing representative strains of Bradyrhizobium japonicum,
      Bradyrhizobium elkanii, and Bradyrhizobium sp. Isolates were also characterized
      by the Biolog system, and the results were compared with the results obtained by
      SDS-PAGE of total proteins; the level of correlation was very low. DNA-rRNA
      hybridizations with 16S or 23S rRNA from Bradyrhizobium japonicum LMG 6138T (T =
      type strain) confirmed that most of the protein electrophoretic clusters belong
      in the Bradyrhizobium-Rhodopseudomonas rRNA complex. Sequencing of 16S rRNA genes
      showed that some of the A. albida-nodulating isolates belong to a separate
      lineage together with representatives of other protein electrophoretic clusters.
      Other isolates that belong to the same electrophoretic cluster as the type strain
      of Bradyrhizobium japonicum are considered members of the lineage represented by
      this type strain. The first lineage is as far removed from Bradyrhizobium
      japonicum as it is from the genus Afipia, Blastobacter denitrificans, and the
      genus Rhodopseudomonas. The possible relationship among electrophoretic group,
      geographic origin, and depth of isolation at a particular site is discussed.

PMID- 7520738
TI  - Phylogenetic evidence for transfer of pentachlorophenol-mineralizing Rhodococcus
      chlorophenolicus PCP-I(T) to the genus Mycobacterium.
AB  - We determined the nucleotide sequence of a 16S rRNA gene of Rhodococcus
      chlorophenolicus PCP-I(T) (= DSM 43826T) (T = type strain). Sequence comparisons
      revealed that there was a close relationship between strain PCP-I(T) and strains
      belonging to the genus Mycobacterium. The sequence data were used to construct a
      phylogenetic tree, which showed that Mycobacterium chubuense is the closest
      relative of strain PCP-I(T). We propose that strain PCP-I(T) should be
      transferred to the genus Mycobacterium and renamed Mycobacterium chlorophenolicum
      PCP-I(T) comb. nov.

PMID- 7520740
TI  - Phylogenetic analysis of a new LL-diaminopimelic acid-containing coryneform
      bacterium from herbage, Nocardioides plantarum sp. nov.
AB  - The 16S rRNA gene sequence of a previously undescribed LL-diaminopimelic acid
      containing coryneform bacterium isolated from herbage was determined in order to
      clarify the taxonomic position of this organism. A comparative sequence analysis
      revealed that the bacterium represents a new line of descent within the genus
      Nocardioides. On the basis of the results of a phylogenetic analysis and the
      phenotypic distinctiveness of the organism, a new species, Nocardioides
      plantarum, is proposed. The type strain is NCIMB 12834.

PMID- 7520739
TI  - Rhizobium ciceri sp. nov., consisting of strains that nodulate chickpeas (Cicer
      arietinum L.).
AB  - The taxonomic status of 16 collection strains of chickpea (Cicer arietinum L.)
      rhizobia which were previously determined to belong to two groups (groups A and
      B) were compared with reference strains belonging to different genera and species
      of the family Rhizobiaceae. We used the following taxonomic, phylogenetic, and
      phenotypic characteristics and approaches to study these organisms: DNA homology,
      guanine-plus-cytosine content, restriction fragment length polymorphism of the
      amplified 16S-intergenic spacer rRNA gene, partial 16S rRNA sequencing, and
      auxanographic tests performed with 147 carbon sources. Similar groups of chickpea
      strains were identified by the different approaches. The chickpea strains were
      found to belong to the genus Rhizobium regardless of the phylogenetic group to
      which they belonged (group A or B). All strains fell into a tight cluster which
      included Rhizobium loti and Rhizobium galegae, and the group B strains were
      closely related to R. loti. An analysis of partial 16S ribosomal DNA sequences
      revealed identical nucleotide sequences for the slowly growing strains and fast
      growing strains that were used as representatives of groups A and B,
      respectively, and these organisms fell into the Rhizobium-Agrobacterium lineage.
      When the sequences of these organisms were compared with the partial sequences of
      Rhizobium huakuii and R. loti, one- and two-nucleotide mismatches were observed,
      respectively, indicating that the chickpea rhizobia are closely related to these
      two species. The DNA-DNA hybridization data revealed that the chickpea rhizobia
      exhibited low levels of homology (less than 17%) to previously described
      Rhizobium and Bradyrhizobium species. Moreover, when we compared chickpea strains
      to R. loti and R. huakuii, the most closely related species as determined by the
      partial 16S rRNA sequence analysis, the homology values ranged from 21 to 52% and
      the delta Tm values were greater than 5 degrees C (delta Tm is the difference
      between the denaturation temperatures of the heterologous and homologous
      duplexes). These results confirmed that the rhizobia that nodulate chickpeas
      cannot be assigned to a previously described species. Within the chickpea
      rhizobia, the DNA homology values obtained when members of groups A and B were
      compared were less than 38%, indicating that the group A and group B organisms
      belong to different species. Furthermore, these organisms can be distinguished
      from each other by the results of phenotypic tests. We propose that the group B
      chickpea rhizobia should be assigned to a new species, Rhizobium ciceri; UPM-Ca7
      is the type strain of R. ciceri.

PMID- 7520741
TI  - Evolutionary relationships among eubacterial groups as inferred from GroEL
      (chaperonin) sequence comparisons.
AB  - The essential GroEL proteins represent a subset of molecular chaperones
      ubiquitously distributed among species of the eubacterial lineage, as well as in
      eukaryote organelles. We employed these highly conserved proteins to infer
      eubacterial phylogenies. GroEL from the species analyzed clustered in distinct
      groups in evolutionary trees drawn by either the distance or the parsimony
      method, which were in general agreement with those found by 16S rRNA comparisons
      (i.e., proteobacteria, chlamydiae, bacteroids, spirochetes, firmicutes [gram
      positive bacteria], and cyanobacteria-chloroplasts). Moreover, the analysis
      indicated specific relationships between some of the aforementioned groups which
      appeared not to be clearly defined or controversial in rRNA-based phylogenetic
      studies. For instance, a monophyletic origin for the low-G+C and high-G+C
      subgroups among the firmicutes, as well as their specific relationship to the
      cyanobacteria-chloroplasts, was inferred. The general observations suggest that
      GroEL proteins provide valuable evolutionary tools for defining evolutionary
      relationships among the eubacterial lineage of life.

PMID- 7520742
TI  - Isolation and characterization of Halothermothrix orenii gen. nov., sp. nov., a
      halophilic, thermophilic, fermentative, strictly anaerobic bacterium.
AB  - The occurrence of thermophilic, halophilic anaerobic bacteria in the sediment of
      a Tunisian salted lake was tested in samples collected at 20-cm intervals down to
      a depth of 1.20 m. A long rod, present only in the 40- to 60-cm layer, was
      isolated at 60 degrees C in a medium containing 100 g of NaCl per liter and
      designated strain H168. This strain produced acetate, ethanol, H2, and CO2 from
      glucose metabolism. Fructose, xylose, ribose, cellobiose, and starch were also
      oxidized. The optimum temperature for growth was 60 degrees C. No growth was
      obtained at 42 or 70 degrees C. Strain H168 grew optimally in NaCl concentrations
      ranging from 50 to 100 g per liter, with the upper and lower limits of growth
      around 200 and 40 g per liter, respectively. The G+C ratio of the DNA was 39.6
      mol%. Although halophilic, moderately thermophilic bacteria have been
      characterized among anaerobes, particularly within methanogens, strain H168 is
      the first true thermophilic (growing above 60 degrees C) halophilic anaerobic
      bacterium described so far. The phylogeny, physiology, morphology, lipid content,
      and high G+C content of strain H168 are sufficiently different from those of
      genera belonging to the family Haloanaerobiaceae to justify the definition of a
      new genus.

PMID- 7520743
TI  - Phylogeny of Helicobacter isolates from bird and swine feces and description of
      Helicobacter pametensis sp. nov.
AB  - Previously, nine fecal isolates from wild birds and a domestic swine were
      identified as helicobacters by phenotypic characterization and reaction with a
      helicobacter genus-specific DNA probe. These isolates fell into three biotypes by
      analysis of phenotypic traits. To further characterize these isolates, full 16S
      rRNA sequences were determined for strains representing each biotype, and
      sequence comparison indicated that the strains represented three novel,
      phylogenetically defined Helicobacter species. Three 16S rRNA-based DNA probes
      were designed and used to identify the remaining strains. Probe reactivity
      divided the strains into the same three groups identified phenotypically. Six of
      the isolates represented a new species of the genus Helicobacter for which we
      propose the name Helicobacter pametensis sp. nov. The following phenotypic
      features distinguished H. pametensis from other Helicobacter and Campylobacter
      species: positive tests for oxidase, catalase, alkaline phosphatase, nitrate
      reduction, growth at 42 degrees C, and growth in the presence of 1% glycine;
      negative tests for urease, gamma glutamyl transpeptidase, indoxyl acetate
      hydrolysis, and hippurate hydrolysis; and susceptibility to nalidixic acid and
      cephalothin. H. pametensis cells were motile and possessed one subterminal
      sheathed flagellum at each end. The two additional Helicobacter species were
      similar to H. pametensis except that they were urease positive, hydrolyzed
      indoxyl acetate, and were resistant to cephalothin. Because these two additional
      species are phenotypically similar and are represented by only two isolates for
      one species and one isolate for the other, they are not formally named but are
      referred to as Helicobacter sp. "Bird-B" and Helicobacter sp. "Bird-C."(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7520744
TI  - Haloanaerobium salsugo sp. nov., a moderately halophilic, anaerobic bacterium
      from a subterranean brine.
AB  - A strictly anaerobic, moderately halophilic, gram-negative bacterium was isolated
      from a highly saline oil field brine. The bacterium was a non-spore-forming,
      nonmotile rod, appearing singly, in pairs, or occasionally as long chains, and
      measured 0.3 to 0.4 by 2.6 to 4 microns. The bacterium had a specific requirement
      for NaCl and grew at NaCl concentrations of between 6 and 24%, with optimal
      growth at 9% NaCl. The isolate grew at temperatures of between 22 and 51 degrees
      C and pH values of between 5.6 and 8.0. The doubling time in a complex medium
      containing 10% NaCl was 9 h. Growth was inhibited by chloramphenicol,
      tetracycline, and penicillin but not by cycloheximide or azide. Fermentable
      substrates were predominantly carbohydrates. The end products of glucose
      fermentation were acetate, ethanol, CO2, and H2. The major components of the
      cellular fatty acids were C14:0, C16:0, C16:1, and C17:0 cyc acids. The DNA base
      composition of the isolate was 34 mol% G+C. Oligonucleotide catalog and sequence
      analyses of the 16S rRNA showed that strain VS-752T was most closely related to
      Haloanaerobium praevalens GSLT (ATCC 33744), the sole member of the genus
      Haloanaerobium. We propose that strain VS-752 (ATCC 51327) be established as the
      type strain of a new species, Haloanaerobium salsugo, in the genus
      Haloanaerobium.

PMID- 7520745
TI  - Phylogenetic analysis of species of the meso-diaminopimelic acid-containing
      genera Brevibacterium and Dermabacter.
AB  - 16S rRNA gene sequencing studies were performed on Dermabacter hominis and four
      meso-diaminopimelic acid-containing species of the genus Brevibacterium.
      Phylogenetic analysis revealed a close association between Dermabacter hominis
      and representatives of the lysine-containing genera Arthrobacter, Micrococcus,
      and Renibacterium. By contrast, the genus Brevibacterium formed a distinct line
      of descent within the high-guanine-plus-cytosine-containing actinomycetes,
      displaying no specific affinity with any other organism examined.

PMID- 7520746
TI  - Phylogenetic placement of Sarcina ventriculi and Sarcina maxima within group I
      Clostridium, a possible problem for future revision of the genus Clostridium.
      Request for an opinion.
AB  - The 16S rRNA gene sequences of Sarcina ventriculi DSM 286T (T = type strain) and
      Sarcina maxima DSM 316T were determined. Phylogenetic analysis revealed that
      these two species are closely related to each other and belong to group I
      Clostridium (sensu Johnson and Francis). The implications of these phylogenetic
      findings for future revision of the genus Clostridium are discussed.

PMID- 7520747
TI  - Polymorphonuclear leukocyte-induced vasocontraction and endothelial dysfunction.
      Role of selectins.
AB  - The roles of selectin adhesion molecules (P- and L-selectin) and their
      counterreceptor sialyl Lewisx were investigated in polymorphonuclear leukocyte
      (PMN)-induced cat coronary vasocontraction and endothelial dysfunction.
      Unstimulated autologous PMNs (10(6) cells/mL) were added to organ chambers
      containing cat coronary artery rings stimulated with either thrombin (2 U/mL) or
      hydrogen peroxide (100 mumol/L). PMNs elicited a significant vasocontraction in
      thrombin- (119 +/- 14 mg) and hydrogen peroxide- (132 +/- 15 mg) stimulated
      coronary rings. This PMN-induced vasocontraction was significantly attenuated by
      pretreatment with either an anti-P-selectin, an anti-L-selectin monoclonal
      antibody (ie, MAb PB 1.3 and MAb DREG-200), or a sialyl Lewis(x)-containing
      oligosaccharide (SLe(x)-OS). Endothelial function as assessed by endothelium
      dependent vasorelaxation to acetylcholine was also significantly attenuated after
      PMN-induced vasocontraction in stimulated coronary rings. This endothelial
      dysfunction was significantly prevented by either PB 1.3, DREG-200, or SLe(x)-OS.
      In contrast, endothelium-independent relaxation to acidified sodium nitrite was
      not altered by PMN incubation, indicating that vascular smooth muscle function
      was unaffected. Adherence of PMNs to coronary endothelium also significantly
      increased following stimulation of endothelium with either thrombin or hydrogen
      peroxide, but this was significantly attenuated by PB 1.3, DREG-200, or SLe(x)
      OS. Thus, PMN-endothelial interaction mediated by either selectin adhesion
      molecules (ie, P-selectin and L-selectin) or sialyl Lewis(x) may play an
      important role in PMN-induced vasocontraction and endothelial dysfunction. This
      mechanism may be important in the early endothelial dysfunction observed
      following reperfusion of an ischemic coronary vasculature.

PMID- 7520748
TI  - Potent activation of phosphatidylinositol 3'-kinase by simple phosphotyrosine
      peptides derived from insulin receptor substrate 1 containing two YMXM motifs for
      binding SH2 domains.
AB  - The phosphotyrosine form of the major substrate for the insulin receptor tyrosine
      kinase, insulin receptor substrate 1 (IRS-1), associates with and activates the
      enzyme phosphatidylinositol 3'-kinase (PtdIns 3'-kinase). IRS-1 contains nine
      potential tyrosine phosphorylation sites within YMXM or YXXM sequences known to
      bind to the two SH2 domains on the 85-kDa regulatory subunit of PtdIns 3'-kinase.
      We used sequences within IRS-1 as a model for synthesizing phosphotyrosine and
      nonhydrolyzable phosphonotyrosine peptides containing two YMXM motifs and tested
      them for their ability to bind to the SH2 domains of PtdIns 3'-kinase and
      stimulate its activity. We demonstrated for the first time that IRS-1-derived
      peptides containing two tyrosine phosphorylated YMXM motifs are capable of
      stimulating PtdIns 3'-kinase activity in the cytosol of 3T3-L1 adipocytes at
      nanomolar concentrations, similar to that required by purified phosphoryl-IRS-1
      [Lamphere, M., Carpenter, C. L., Sheng, Z., Kallen, R. G., & Lienhard, G. E.
      (1994) Am. J. Physiol. 266 (Endocrinol. Metab. 29), E486-E489] and the extent of
      activation by these peptides was similar to that seen by maximal stimulation of
      cells with insulin. In contrast, those phosphotyrosine peptides containing only a
      single YMXM motif were able to stimulate PtdIns 3'-kinase activity only at
      concentrations over 10 microM. We conclude from these results that the high
      affinity activation of PtdIns 3'-kinase requires the simultaneous binding of two
      phosphorylated YMXM motifs on IRS-1 to the two SH2 domains of PtdIns 3'-kinase.

PMID- 7520750
TI  - Importance of loops of mitochondrial ADP/ATP carrier for its transport activity
      deduced from reactivities of its cysteine residues with the sulfhydryl reagent
      eosin-5-maleimide.
AB  - The effects of various compounds such as the transport substrate ADP and the
      transport inhibitors carboxyatractyloside (CATR) and bongkrekic acid (BKA) on the
      labeling of cysteine residues in the ADP/ATP carrier of bovine heart
      submitochondrial particles by the SH reagent eosin-5-maleimide (EMA) were
      studied. Of the four cysteine residues in the carrier, the labeling of Cys159 by
      EMA progressed predominantly and rapidly, and those of Cys56 and Cys256
      moderately, but Cys128 was not labeled, as we reported previously [Majima, E., et
      al. (1993) J. Biol. Chem. 268, 22181-22187]. ADP inhibited the labelings of
      Cys56, Cys159, and Cys256 by EMA. BKA markedly inhibited the labeling of Cys159
      by EMA, and also the labeling of Cys256, but did not affect the labeling of
      Cys56, suggesting that it binds from the matrix side to a region close to Cys159
      in the second loop facing the matrix space. CATR completely inhibited the
      labeling by EMA when added on the cytosolic side, but had no effect when added on
      the matrix side. From these results, the conformational changes of the carrier
      induced by CATR, BKA, and ADP are discussed. Furthermore, a mechanism of adenine
      nucleotide transport through the ADP/ATP carrier in association with change in
      its conformation is proposed.

PMID- 7520749
TI  - Mapping the lipoyl groups of the pyruvate dehydrogenase complex by use of gold
      cluster labels and scanning transmission electron microscopy.
AB  - This paper describes the organization of lipoyl moieties within the pyruvate
      dehydrogenase (PDH) complex from Escherichia coli as studied in the scanning
      transmission electron microscope (STEM). The PDH complex is a multienzyme complex
      consisting of E1, pyruvate dehydrogenase, E2, dihydrolipoyl transacetylase, and
      E3, dihydrolipoyl dehydrogenase. The core of the complex is the cubic 24-subunit
      E2 component, which contains the lipoyl moieties bonded to lipoyl-bearing
      domains. E1 and E3 are associated along the edges (E1) and on the faces (E3) of
      the core. The lipoyl moieties were reduced with NADH and alkylated with a p
      maleimidobenzoyl undecagold cluster complex. The gold labels were found to be
      bound very nearly specifically by dihydrolipoyl transacetylase (E2). Undecagold
      clusters were imaged directly by the STEM and also digitally mapped by radial
      mass analysis. The mass of the E2E3 subcomplex is about half that of the PDH
      complex. The PDH complex and GC-PDH are both about 420 A in diameter, as
      determined by radial mass analysis, and the E2E3 subcomplex and GC-E2E3 are 320
      and 350 A, respectively. The outer boundary of the E2E3 subcomplex was clearly
      shown in STEM micrographs by the undecagold labels in GC-E2E3. Data obtained from
      radial mass analysis of GC-E2E3 and the unlabeled E2E3 subcomplex also showed
      that the size of the subcomplex is extended by the lipoyl-bearing domains
      surrounding the central E2 core. The capabilities of lipoyl moieties to undergo
      translocation over long distances through structural mobility in the lipoyl
      bearing domains was confirmed by the observation that many of the lipoyl groups
      in E2E3 subcomplexes relax outward into space vacated by the removal of E1 during
      the preparation of the subcomplex from PDH complex. Radial mass analysis of the
      PDH complex and GC-PDH indicates that lipoyl groups are distributed over a large
      region of the PDH complex, extending from the central core to 170-180 A from the
      center of the complex, with the highest density at about 75 A from the particle
      centers, near the interface between E2 and the associated components E1 and E3.

PMID- 7520751
TI  - Multivalent ligand-receptor binding interactions in the fibroblast growth factor
      system produce a cooperative growth factor and heparin mechanism for receptor
      dimerization.
AB  - The binding interactions for the three primary reactants of the fibroblast growth
      factor (FGF) system, basic FGF (bFGF), an FGF receptor, FGFR1, and the cofactor
      heparin/heparan sulfate (HS), were explored by isothermal titrating calorimetry,
      ultracentrifugation, and molecular modeling. The binding reactions were first
      dissected into three binary reactions: (1) FGFR1 + bFGF<==>FGFR1/bFGF, K1 = 41
      (+/- 12) nM; (2) FGFR1 + HS<==>FGFR1/HS, K2 = 104 (+/- 17) microM; and (3) bFGF +
      HS<==>bFGF/HS, K3 = 470 (+/- 20) nM, where HS = low MW heparin, approximately 3
      kDa. The first, binding of bFGF to FGFR1 in the absence of HS, was found to be a
      simple binary binding reaction that is enthalpy dominated and characterized by a
      single equilibrium constant, K1. The conditional reactions of bFGF and FGFR1 in
      the presence of heparin were then examined under conditions that saturate only
      the bFGF heparin site (1.5 equiv of HS/bFGF) or saturate the HS binding sites of
      both bFGF and FGFR1 (1.0 mM HS). Both 3-and 5-kDa low MW heparins increased the
      affinity for FGFR1 binding to bFGF by approximately 10-fold (Kd = 4.9 +/- 2.0
      nM), relative to the reaction with no HS. In addition, HS, at a minimum of 1.5
      equiv/bFGF, induced a second FGFR1 molecule to bind to another lower affinity
      secondary site on bFGF (K4 = 1.9 +/- 0.7 microM) in an entropy-dominated reaction
      to yield a quaternary complex containing two FGFR1, one bFGF, and at least one
      HS. Molecular weight estimates by analytical ultracentrifugation of such fully
      bound complexes were consistent with this proposed composition. To understand
      these binding reactions in terms of structural components of FGFR1, a three
      dimensional model of FGFR1 was constructed using segment match modeling.
      Electrostatic potential calculations confirmed that an elongated cluster,
      approximately 15 x 35 A, of nine cationic residues focused positive potential
      (+2kBT) to the solvent-exposed beta-sheet A, B, E, C' surface of the D(II) domain
      model, strongly implicating this locus as the HS binding region of FGFR1.
      Structural models for HS binding to FGFR1, and HS binding to bFGF, were built
      individually and then assembled to juxtapose adjacent binding sites for receptor
      and HS on bFGF, against matching proposed growth factor and HS binding sites on
      FGFR1. The calorimetric binding results and the molecular modeling exercises
      suggest that bFGF and HS participate in a concerted bridge mechanism for the
      dimerization of FGFR1 in vitro and presumably for mitogenic signal transduction
      in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7520752
TI  - Iron(II) bleomycin-mediated degradation of a DNA-RNA heteroduplex.
AB  - The effect of iron(II) bleomycin on a DNA-RNA heteroduplex was investigated using
      a substrate formed by reverse transcription of Escherichia coli 5S ribosomal RNA.
      Both strands of the heteroduplex were cleaved by FeII.BLM A2 at comparable
      concentrations; complete digestion of both strands was observed using 5 microM
      FeII.BLM A2. The DNA strand of the heteroduplex was cleaved predominantly at 5'-G
      pyr-3' sites; the sites of cleavage of the DNA strand were a subset of those
      observed for the corresponding DNA strand of a DNA duplex of identical sequence.
      The sites of cleavage of the RNA strand of the heteroduplex involved both purines
      and pyrimidines and were found to be different than the sites of cleavage of the
      5S rRNA alone, demonstrating that cleavage of the former must actually have
      involved heteroduplex recognition by FeII.BLM A2. Both the DNA and RNA strands of
      the heteroduplex were cleaved by FeII.BLM A2 in the presence of physiological
      concentrations of Mg2+, consistent with the possibility that DNA-RNA
      heteroduplexes may be therapeutically relevant targets for bleomycin.

PMID- 7520753
TI  - A kinetic mechanism for cleavage of precursor tRNA(Asp) catalyzed by the RNA
      component of Bacillus subtilis ribonuclease P.
AB  - A kinetic mechanism is presented for the cleavage of Bacillus subtilis precursor
      tRNA(Asp) catalyzed by the RNA component of B. subtilis ribonuclease P (RNase P)
      under optimal conditions (50 mM Tris Cl (pH 8.0), 100 mM MgCl2, and 800 mM NH4Cl,
      37 degrees C). This kinetic mechanism was derived from measuring pre-steady
      state, steady-state, single-turnover, and binding kinetics using a combination of
      quench-flow, gel filtration, and gel shift techniques. A minimal kinetic
      description involves the following: (1) binding of pre-tRNA(Asp) to RNase P RNA
      rapidly (6.3 x 10(6) M-1 s-1), but slower than the diffusion-controlled limit;
      (2) cleavage of the phosphodiester bond with a rate constant of 6 s-1; (3)
      dissociation of products in a kinetically preferred pathway, with the 5' RNA
      fragment dissociating first (> or = 0.2 s-1) followed by rate-limiting tRNA
      dissociation (0.02 s-1); and (4) formation of a second conformer of RNase P RNA
      during the catalytic cycle that is less stable and binds pre-tRNA(Asp)
      significantly more slowly (7 x 10(4) M-1 s-1). This scheme involves the isolation
      of individual steps in the reaction sequence, is consistent with steady-state
      data, and pinpoints the rate-determining step under a variety of conditions. This
      kinetic mechanism will facilitate a more accurate definition of the role of
      metals, pH, and the protein component in each step of the reaction and provide an
      essential background for understanding the influence of structural changes on the
      catalytic activity.

PMID- 7520754
TI  - Topology of CNS myelin proteolipid protein: evidence for the nonenzymatic
      glycosylation of extracytoplasmic domains in normal and diabetic animals.
AB  - Myelin proteolipid protein (PLP), the main integral membrane protein in the
      central nervous system myelin, was labeled at the extracytoplasmic domains with
      the membrane impermeant reagents pyridoxal 5'-phosphate and tritiated
      borohydride. Lysine-217, located in the fourth hydrophilic domain of PLP, was
      found to be the major labeled residue, which defined this domain to be
      extracytoplasmic in agreement with our previously proposed topological model. The
      remarkably high reactivity in vitro of this residue as compared to all other
      lysines in PLP led us to investigate the possible modification of PLP in vivo by
      other carbonyl compounds. We demonstrate that PLP is the most highly
      nonenzymatically glycosylated membrane protein in murine and bovine brain. The
      degree of modification increases significantly under hyperglycemic conditions, as
      studied in diabetic mice. The majority of the glycosylation sites are also
      located at extracytoplasmic domains. The degree of nonenzymatic glycosylation of
      PLP may be related to late diabetic complications affecting the central nervous
      system.

PMID- 7520755
TI  - Inhibition of receptor binding by high-affinity RNA ligands to vascular
      endothelial growth factor.
AB  - The proliferation of new blood vessels (angiogenesis) is a process that
      accompanies many pathological conditions including rheumatoid arthritis and solid
      tumor growth. Among angiogenic cytokines that have been identified to date,
      vascular endothelial growth factor (VEGF) is one of the most potent. We used
      SELEX [systematic evolution of ligands by exponential enrichment; Tuerk, C., &
      Gold, L. (1990) Science 249, 505-510] to identify RNA ligands that bind to VEGF
      in a specific manner with affinities in the low nanomolar range. Ligands were
      selected from a starting pool of about 10(14) RNA molecules containing 30
      randomized positions. Isolates from the affinity-enriched pool were grouped into
      six distinct families on the basis of primary and secondary structure
      similarities. Minimal sequence information required for high-affinity binding to
      VEGF is contained in 29-36-nucleotide motifs. Binding of truncated (minimal) high
      affinity ligands to VEGF is competitive with that of other truncated ligands and
      heparin. Furthermore, truncated ligands from the six ligand families inhibit
      binding of [125I]VEGF to its cell-surface receptors. Oligonucleotide ligands
      described here represent an initial set of lead compounds in our ongoing effort
      toward the development of potent and specific VEGF antagonists.

PMID- 7520757
TI  - Staining mast cells for morphometric evaluation on an image analysis system.
AB  - Multiple skin sections from three nonhuman primates (Macaca mulatta) and three
      hairless guinea pigs (Cavia porcellus) were stained with 12 different histologic
      stains to determine whether mast cells could be selectively stained for
      morphometric analysis using an image analysis system (IAS). Sections were first
      evaluated with routine light microscopy for mast cell granule staining and the
      intensity of background staining. Methylene blue-basic fuchsin and Unna's method
      for mast cells (polychrome methylene blue with differentiation in glycerin-ether)
      stained mast cell granules more intensely than background in both species.
      Toluidine blue-stained sections in the guinea pig yielded similar results.
      Staining of the nuclei of dermal connective tissue was enhanced with the
      methylene blue-basic fuchsin and toluidine blue stains. These two stains, along
      with the Unna's stain, were further evaluated on an IAS with and without various
      interference filters (400.5-700.5 nm wavelengths). In both the methylene blue
      basic fuchsin and toluidine blue stained sections, mast cell granules and other
      cell nuclei were detected together by the IAS. The use of interference filters
      with these two stains did not distinguish mast cell granules from stained nuclei.
      Unna's stain was the best of the 12 stains evaluated because mast cell granule
      staining was strong and background staining was faint. This contrast was further
      enhanced by interference filters (500.5-539.5 nm) and allowed morphometric
      measurements of mast cells to be taken on the IAS without background
      interference.

PMID- 7520756
TI  - Ineffectiveness of the inhibition of the main haemorrhagic metalloproteinase from
      Bothrops jararaca venom by its only plasma inhibitor, alpha 2-macroglobulin.
AB  - Observations that a haemorrhagic metalloproteinase (jararhagin) from Bothrops
      jararaca venom had less effect on platelets suspended in plasma than in washed
      platelet suspensions, suggested that plasma contains naturally occurring
      inhibitor(s) of this enzyme. By using radiolabelled jararhagin and crossed
      immunoelectrophoresis, we have demonstrated the binding of this enzyme to alpha 2
      macroglobulin in plasma. SDS-PAGE analysis of this binding revealed the presence
      of radioactivity in four bands with relative molecular masses of 640, 570, 520
      and 410 kDa; in addition a small amount of 47 kDa free enzyme was demonstrable.
      Reduced samples showed an additional non-complexed 90 kDa fragment of alpha 2
      macroglobulin generated by jararhagin. These results are compatible with a model
      in which, upon multiple cleavages of alpha 2-macroglobulin, the enzyme becomes
      covalently bound to the inhibitor, and the two halves of the inhibitor become
      crosslinked. However, jararhagin activity was not completely inhibited even after
      long incubation (60 min) with a large (10-fold) molar excess of alpha 2
      macroglobulin either in plasma or a purified alpha 2-macroglobulin preparation.
      Kinetic studies showed that inhibition was comparatively slow, although
      jararhagin readily cleaved alpha 2-macroglobulin in the bait region. Therefore,
      the ineffectiveness of the inhibition could have resulted from a low tendency of
      this proteinase to form covalent complexes with the inhibitor. We conclude that
      the pronounced haemorrhagic activity of jararhagin can be attributed to prolonged
      access of this enzyme to high molecular weight substrates, even in the presence
      of a large molar excess of alpha 2-macroglobulin.

PMID- 7520758
TI  - Hoechst 33258 staining for detecting mycoplasma contamination in cell cultures: a
      method for reducing fluorescence photobleaching.
AB  - DNA fluorochrome staining with Hoechst 33258 bisbenzimide is commonly used for
      detection of mycoplasma contamination in cell cultures. Photobleaching of Hoechst
      33258 is pronounced under the conditions of intense illumination, high
      magnification and resolution required for detection of mycoplasmas. To reduce
      photobleaching we investigated the effects of some antioxidant molecules, p
      phenylenediamine (PPD), n-propyl gallate (NPG) and 1,4-diazabicyclo(2,2,2)octane
      (DABCO), which are known to reduce the fading rate of fluorescein. Mycoplasma
      contaminated cell monolayers were stained with Hoechst 33258 and mounted in
      glycerol containing different amounts of antioxidant additives. The cells were
      examined in an epifluorescence microscope, and the emitted light intensity was
      recorded. Results showed that PPD and, to a lower degree, NPG, retarded the
      photobleaching of Hoechst 33258-stained cells, whereas DABCO was not effective.
      However, fluorescence half-life was increased about three-fold by NPG and almost
      20-fold by PPD. The rate of fluorescence fading of Hoechst 33258 can therefore be
      retarded by PPD, with obvious advantages for reading and photographic recording
      of results.

PMID- 7520759
TI  - Naphthalene black staining of granules of eosinophilic granulocytes: proposed
      mechanism of action using chemical blockade and computer graphics.
AB  - Histochemical staining of the granules of eosinophilic granulocytes and
      subsequent blockade of the reaction by alkaline benzyl was strongly suggestive
      that in its purified form, the diazo dye naphthalene black reacts with tissue
      sites containing high concentrations of arginine residues. Computer graphics
      modelling indicated that the sulfonate group of the dye reacts electrostatically
      with the guanidino functional group of arginine. This acid-base type reaction
      likely has a stoichiometric ratio of 2:1 in favor of the amino acid.

PMID- 7520760
TI  - Supravital uptake of cationic dyes by mast cell granules: a light and electron
      microscope study.
AB  - Methylene blue and neutral red were selected for staining mast cell granules by
      supravital injections. A new technique was applied for embedding in paraffin and
      Araldite without dislocation or loss of dye. Stabilization and electron
      microscopic identification of the dyes were achieved by transforming them into
      electron-dense precipitates using phosphomolybdic acid dissolved in a
      paraformaldehyde-glutaraldehyde mixture to preserve the ultrastructure of the
      tissues. It was found that in general the intensity of the light microscopic
      staining correlated directly with the electron density. Closer study revealed
      that not all cytoplasmic granules exhibited the same strong affinity for the
      cationic dyes. Furthermore, differences in dye distribution were observed within
      the granules themselves. The difference in the staining pattern can be explained
      by the heterogeneous occurrence of the anionic residues. Because of its high
      sensitivity and relatively low toxicity, the method described here is well suited
      for detecting the binding sites of organic cations in tissues under supravital or
      vital conditions.

PMID- 7520761
TI  - Adverse effects of muscle relaxants.

PMID- 7520762
TI  - Non-prostanoid prostacyclin mimetics. 6. Derivatives of 2-[3-[2-(4,5-Diphenyl-2
      oxazolyl)ethyl]phenoxy]acetic acid modified beta-to the oxazole ring.
AB  - 2-[3-[2-(4,5-Diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid, 1, has been described
      as a non-prostanoid PGI2 mimetic that demonstrates anti-thrombotic properties of
      long duration in animal models of thrombosis. The effects of substitution and
      modification of the carbon beta-to the oxazole heterocycle of 1 were examined and
      equated with the potency of the compounds as inhibitors of ADP-induced human
      platelet aggregation in vitro. Potency was sensitive to both the size of the
      substituent and the identity of the beta-atom. The carbamates 13c-e demonstrated
      IC50's of 0.28-0.36 microM and were significantly more potent than the progenitor
      1, IC50 = 1.2 microM. The ethyl carbamate 13c displaced [3H]-iloprost from
      platelet membranes in a concentration-dependent fashion that was half maximal at
      20 nM, which compares with IC50's of 171 nM for 1 and 39 nM or unlabelled
      iloprost. Carbamate 13c stimulated platelet adenylate cyclase but the maximal
      effect was less than that observed for PGI2, identifying 13c as a partial agonist
      at the platelet PGI2 receptor.

PMID- 7520763
TI  - Tenascin is synthesized and secreted by rat mesangial cells in culture and is
      present in extracellular matrix in human glomerular diseases.
AB  - Tenascin (TN) is a large oligomeric protein recently described as a component of
      the extracellular matrix. The distribution of TN in adult kidney tissue has not
      been adequately evaluated, but preliminary data have suggested that TN is
      variably seen in rare mesangial areas and in stroma surrounding some tubules. The
      enlargement of the mesangial matrix (mesangial sclerosis) is a common feature of
      many renal diseases and is thought to be partially related to oversynthesis of
      the normal components of the mesangial matrix (collagen type IV, laminin,
      fibronectin, and heparan sulfate proteoglycans) by mesangial cells. However, the
      possibility that mesangial cells are also the source of other extracellular
      matrix proteins that participate in the process of mesangial sclerosis has not
      been explored. In this study, the synthesis of TN by cultured rat mesangial cells
      was documented by the following observations: (1) Northern hybridization of total
      RNA extracted from mesangial cells showed two distinct species of TN mRNA; (2)
      immunoblotting of the protein extracted from the conditioned medium demonstrated
      four TN protein bands; (3) immunoblotting of the protein extracted from the
      mesangial cell lysate demonstrated at least four TN protein bands; and (4)
      immunohistochemical techniques identified TN within the cytoplasm of mesangial
      cells and in the surrounding extracellular matrix.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7520764
TI  - Insulin-like growth factors (IGF) and IGF binding proteins in milk; sources and
      functions.

PMID- 7520765
TI  - [Preparation of monoclonal antibodies to the O-antigen of Salmonella typhimurium
      serogroup B (O-4.5)].

PMID- 7520766
TI  - Modeling human lymphoid precursor cell gene therapy in the SCID-hu mouse.
AB  - Gene therapy of human T-lymphocyte disorders, including acquired immunodeficiency
      syndrome (AIDS), would be greatly facilitated by the development of an in vivo
      system in which transduced human hematopoietic stem cells can be used to
      reconstitute the T-lymphoid compartment. Here we use the SCID-hu mouse as a
      recipient for human CD34+ hematopoietic progenitor cells transduced in vitro with
      a retroviral vector carrying the neomycin resistance gene (neoR). The transduced
      cells engraft and reconstitute the lymphoid compartments of the human thymus
      implant with as few as 5 x 10(4) CD34+ cells. The neoR gene was expressed at low
      levels in human thymocytes and there was no apparent effect on thymocyte
      differentiation as a result of vector transduction. Thus, this SCID-hu mouse
      system is the first in vivo model showing human thymopoiesis after transduction
      of exogenous vectors, and should allow preclinical testing of gene therapeutic
      reagents designed to function in human cells of the T-lymphoid lineage. Because
      human immunodeficiency virus type 1 infection induces depletion of human
      thymocytes in SCID-hu mice, this system may be particularly valuable in
      evaluating efficacy of gene therapies to combat AIDS.

PMID- 7520767
TI  - The B7-2 (B70) costimulatory molecule expressed by monocytes and activated B
      lymphocytes is the CD86 differentiation antigen.
AB  - T-cell activation is initiated after T-cell receptor binding to antigen, but also
      requires interactions between costimulatory molecules expressed on antigen
      presenting cells. An important costimulatory molecule expressed by monocytes and
      activated B lymphocytes has been recently identified and termed B7-2 or B70.
      Independently, a new Cluster of Differentiation was defined in the Fifth
      International Leukocyte Differentiation Antigen Workshop as CD86, a molecule
      predominantly expressed by monocytes and activated B lymphocytes. In this study,
      the two monoclonal antibodies that defined CD86, FUN-1 and BU-63, were shown to
      bind to cDNA transfected cells expressing B7-2/B70. The FUN-1 monoclonal antibody
      also completely blocked the costimulatory activity of B7-2/B70 in functional
      assays. Therefore, the serologically defined CD86 differentiation antigen is the
      B7-2/B70 molecule.

PMID- 7520768
TI  - Transfer and expression of the human multiple drug resistance gene in human CD34+
      cells.
AB  - The human multiple-drug resistance (MDR1) gene has been transferred into human
      hematopoietic progenitors using retroviral gene transfer. Human bone marrow cells
      and isolated CD34+ cells isolated from marrow were exposed to growth factors
      interleukin-3 (IL-3), IL-6, and stem cell factor for 48 hours and then to two
      changes of MDR retroviral supernatants over the next 24 hours. Progenitor assays
      in methylcellulose at this time showed that 18% to 70% of BFU-E and 30% to 60% of
      CFU-GM contain the transferred MDR gene by polymerase chain reaction analysis. Up
      to 11.2% of the progeny of these cells express increased amounts of MDR
      glycoprotein on their surface by fluorescence-activated cell sorter (FACS)
      analysis. In addition, transduced cells are enriched in high MDR-expressing cells
      after exposure to taxol as assessed by FACS analysis, and by resistance of BFU-E
      to taxol (Bristol-Myers Squibb, Princeton, NJ). These studies indicate the
      feasibility of using MDR gene transfer as a means of enriching marrow for MDR
      transduced cells. They also provide the basis of a phase 1 clinical protocol in
      patients with advanced cancers not involving the bone marrow for the use of MDR
      gene transfer as a means of protecting marrow cells, which normally express low
      levels of MDR, from the myelosuppressive effects of drugs like taxol.

PMID- 7520769
TI  - Positively selected autologous blood CD34+ cells and unseparated peripheral blood
      progenitor cells mediate identical hematopoietic engraftment after high-dose
      VP16, ifosfamide, carboplatin, and epirubicin.
AB  - To investigate the feasibility of peripheral blood CD34+ cell selection and to
      analyze CD34+ cell-mediated engraftment after high-dose chemotherapy, we
      performed a phase I/II trial in 21 patients with advanced malignancies. The
      rationale for the selection of CD34+ cells from peripheral blood progenitor cell
      (PBPC) collections is based on the observation that contaminating tumor cells can
      be depleted approximately 3 logs using this procedure. CD34+ cells from
      chemotherapy+granulocyte colony-stimulating factor-mobilized PBPCs were
      positively selected with an avidin-biotin immunoadsorption column (CEPRATE SC
      system). One leukapheresis product with a median number of 2.8 x 10(6) CD34+
      cells/kg was labeled with a biotinylated anti-CD34 monoclonal antibody and
      subsequently processed over the column. The yield of selected CD34+ cells was 73%
      +/- 24.6%. The purity of the CD34+ cell fraction was 61.4% +/- 19.7%. CD34+ cells
      were shown to represent predominantly committed progenitors coexpressing CD33,
      CD38, and HLA-DR molecules (lin+). They gave rise to myeloid as well as erythroid
      and multilineage colonies in vitro. In addition, positively selected CD34+ cells
      also comprised early hematopoietic progenitor cells, as shown by the presence of
      CD34+/lin- cells. Transfusion of positively selected CD34+ cells (2.5 x 10(6)
      CD34+/kg; range, 0.45 to 5.1) after high-dose VP16 (1,500 mg/m2), ifosfamide (12
      g/m2), carboplatin (750 mg/m2), and epirubicin (150 mg/m2) (VIC-E) in 15 patients
      resulted in a rapid and stable engraftment of hematopoiesis without any adverse
      events. As compared with 13 historical control patients reconstituted with a
      comparable number of unseparated PBPCs, time to neutrophil and platelet recovery
      was identical in both groups (absolute neutrophil count > 500/microL, day + 12;
      platelet count > 50,000/microL, day + 15). These data indicate that autologous
      peripheral blood CD34+ cells and unseparated PBPCs mediate identical
      reconstitution of hematopoiesis after high-dose VIC-E chemotherapy. Because
      positive selection of CD34+ cells from mobilized blood results in a median 403
      fold depletion of T cells, allogeneic CD34+ cells from mobilized blood should be
      investigated as an alternative to bone marrow cells for allotransplantation.

PMID- 7520770
TI  - A randomized, placebo-controlled trial of recombinant human granulocyte colony
      stimulating factor administration in newborn infants with presumed sepsis:
      significant induction of peripheral and bone marrow neutrophilia.
AB  - Host defenses in the human neonate are limited by immaturity in phagocytic
      immunity. Such limitations seem to predispose infected newborns to neutropenia
      from an exhaustion of the neutrophil reserve. Among the critical defects thus far
      identified in neonatal phagocytic immunity is a specific reduction in the
      capacity of mononuclear cells to express granulocyte colony-stimulating factor (G
      CSF) after stimulation. However, the safety, pharmacokinetics, and biological
      efficacy of administration of recombinant human (rh)G-CSF to infected human
      newborns to compensate for this deficiency is unknown. Forty-two newborn infants
      (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of
      life were randomized to receive either placebo or varying doses of rhG-CSF (1.0,
      5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0
      micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood
      counts with differential and platelet counts were obtained at hours 0, 2, 6, 24,
      48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2,
      6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after
      72 hours for quantification of the bone marrow neutrophil storage pool (NSP),
      neutrophil proliferative pool, granulocyte progenitors, and pluripotent
      progenitors. Functional activation of neutrophils (C3bi expression) was
      determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF
      was not associated with any recognized acute toxicity. RhG-CSF induced a
      significant increase in the blood neutrophil concentration 24 hours after the 5
      and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as
      96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF.
      Neutrophil C3bi expression was significantly increased at 24 hours after 10
      micrograms/kg every 24-hour dose of rhG-CSF. The half-life of rhG-CSF was 4.4 +/-
      0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The
      rhG-CSF induced a significant increase in the peripheral blood and bone marrow
      absolute neutrophil concentration and in C3bi expression. Future clinical trials
      aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia
      in newborn infants might include the use of rhG-CSF.

PMID- 7520771
TI  - CD34+/CD33- cells reselected from macrophage inflammatory protein 1
      alpha+interleukin-3--supplemented "stroma-noncontact" cultures are highly
      enriched for long-term bone marrow culture initiating cells.
AB  - Human hematopoietic stem cells are thought to express the CD34 stem cell antigen,
      low numbers of HLA-DR and Thy1 antigens, but no lineage commitment antigens,
      CD38, or CD45RA antigens. However, fluorescence-activated cell sorted CD34+
      subpopulations contain not more than 1% to 5% primitive progenitors capable of
      initiating and sustaining growth in long-term bone marrow culture initiating
      cells (LTBMC-ICs). We have recently shown that culture of fresh human marrow
      CD34+/HLA-DR- cells separated from a stromal layer by a microporous membrane
      ("stroma-noncontact" culture) results in the maintenance of 40% of LTBMC-ICs. We
      hypothesized that reselection of CD34+ subpopulations still present after several
      weeks in stroma-noncontact cultures may result in the selection of cells more
      highly enriched for human LTBMC-ICs. Fresh marrow CD34+/HLA-DR- cells were
      cultured for 2 to 3 weeks in stroma-noncontact cultures. Cultured progeny was
      then sorted on the basis of CD34, HLA-DR, or CD33 antigen expression, and sorted
      cells evaluated for the presence of LTBMC-ICs by limiting dilution analysis. We
      show that (1) LTBMC-ICs are four times more frequent in cultured CD34+/HLA-DR-
      cells (4.6% +/- 1.7%) than in cultured CD34+/HLA-DR- cells (1.3% +/- 0.4%). This
      suggests that HLA-DR antigen expression may depend on the activation status of
      primitive cells rather than their lineage commitment. We then sorted cultured
      cells on the basis of the myeloid commitment antigen, CD33. (2) These studies
      show that cultured CD34+/CD33- cells contain 4% to 8% LTBMC-ICs, whereas cultured
      CD34+/CD33+bright cells contain only 0.1% +/- 0.03% LTBMC-ICs. Because LTBMC-ICs
      are maintained significantly better in stroma-noncontact cultures supplemented
      with macrophage inflammatory protein 1 alpha (MIP-1 alpha) and interleukin-3 (IL
      3) (Verfaillie et al, J Exp Med 179:643, 1994), we evaluated the frequency of
      LTBMC-ICs in CD34+/CD33- cells present in such cultures. (3) CD34+/CD33- cells
      present in MIP-1 alpha + IL-3-supplemented cultures contain up to 30% LTBMC-ICs.
      The increased frequency of LTBMC-ICs in cultured CD34+ subpopulations may be the
      result of terminal differentiation of less primitive progenitors, loss of cells
      that fail to respond to the culture conditions or recruitment of quiescent LTBMC
      ICs. The capability to select progenitor populations containing up to 30% LTBMC
      ICs should prove useful in studies examining the growth requirements, self
      renewal, and multilineage differentiation capacity of human hematopoietic stem
      cells at the single-cell level.

PMID- 7520772
TI  - Stem cell factor and interleukin-7 synergize to enhance early myelopoiesis in
      vitro.
AB  - Interleukin-7 (IL-7) has been shown to be a critical factor in murine lymphoid
      development. It stimulates pre-B cells to divide in the absence of stroma cells
      and it is an important growth regulator of immature and mature T cells. IL-7 has
      been shown to synergize with stem cell factor (SCF) to provide a potent growth
      stimulus for pre-B cells. However, the combined effects of IL-7 and SCF on murine
      primitive hematopoietic cells in vitro have not been established. In the present
      study, the effects of recombinant rat (rr) SCF and recombinant human (rh) IL-7 on
      primitive murine bone marrow progenitors (Lin-Sca1+) were investigated in single
      cell cloning experiments. rhIL-7 alone had no proliferative effect on Lin-Sca1+
      cells, but in a dose-dependent manner directly enhanced rrSCF-induced colony
      formation, with an average increase in colony numbers of 2.7-fold. Interestingly,
      the cells formed in response to SCF and IL-7 were predominantly mature
      granulocytes. Thus, SCF and IL-7 synergize to stimulate early myelopoiesis in
      vitro.

PMID- 7520773
TI  - Functional differences between CD38- and DR- subfractions of CD34+ bone marrow
      cells.
AB  - Several studies have previously demonstrated enrichment in primitive progenitor
      cells in subfractions of CD34+ bone marrow (BM) cells not expressing CD38 or HLA
      DR (DR) antigens. However, no studies have directly compared these two cell
      populations with regard to their content of primitive and more committed
      progenitor cells. Flow cytometric analysis of immunomagnetic isolated CD34+ cells
      demonstrated little overlap between CD34+CD38- and CD34+DR- progenitor
      subpopulations in that only 12% to 14% of total CD34+DR- and CD34+CD38- cells
      were double negative (CD34+CD38-DR-). Although the number of committed myeloid
      progenitor cells (colony-forming units granulocyte-macrophage) was reduced in
      both subpopulations, only CD34+CD38- cells were significantly depleted in
      committed erythroid progenitor cells (burst-forming units-erythroid). In single
      cell assay, CD34+CD38- cells showed consistently poorer response to single as
      opposed to multiple hematopoietic growth factors as compared with unfractionated
      CD34+ cells, indicating that the CD34+CD38- subset is relatively enriched in
      primitive hematopoietic progenitor cells. Furthermore, CD34+CD38- and CD34+DR-
      cells, respectively, formed 3.2-fold and 1.6-fold more high proliferative
      potential colony-forming cell (HPP-CFC) colonies than did unfractionated CD34+
      cells. Finally, CD34+CD38-DR- cells were depleted in HPP-CFCs as compared with
      CD34+CD38+DR+ cells. The results of the present study suggest that both the CD38-
      and DR- subfractions of CD34+ bone marrow cells are enriched in primitive
      hematopoietic progenitor cells, with the CD34+CD38- subpopulation being more
      highly enriched than CD34+DR- cells.

PMID- 7520774
TI  - Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells
      mobilized into the peripheral blood by treatment with granulocyte colony
      stimulating factor and stem cell factor.
AB  - Cytokine-mobilized peripheral blood cells have been shown to participate in
      hematopoietic recovery after bone marrow (BM) transplantation, and are proposed
      to be useful targets for retrovirus-mediated gene transfer protocols. We treated
      mice with granulocyte colony-stimulating factor (G-CSF) and stem cell factor
      (SCF) to mobilize hematopoietic progenitor cells into the peripheral blood. These
      cells were analyzed for the number and frequency of pluripotent hematopoietic
      stem cells (PHSC). We found that splenectomized animals treated for 5 days with G
      CSF and SCF showed a threefold increase in the absolute number of PHSC over
      normal mice. The number of peripheral-blood PHSC increased 250-fold from 29 per
      untreated mouse to 7,200 in peripheral-blood PHSC in splenectomized animals
      treated for 5 days with G-CSF and SCF. Peripheral blood PHSC mobilized by
      treatment with G-CSF and SCF were analyzed for their ability to be transduced by
      retroviral vectors. Peripheral-blood PHSC from splenectomized animals G-CSF and
      SCF were transduced with a recombinant retrovirus containing the human MDR-1
      gene. The frequency of gene transfer into peripheral blood PHSC from animals
      treated for 5 and 7 days was two-fold and threefold higher than gene transfer
      into PHSC from the BM of 5-fluorouracil-treated mice (P < .01). We conclude that
      peripheral blood stem cells mobilized by treatment with G-CSF and SCF are
      excellent targets for retrovirus-mediated gene transfer.

PMID- 7520775
TI  - Stromal cell lines derived from LP-BM5 murine leukemia virus-infected long-term
      bone marrow cultures impair hematopoiesis in vitro.
AB  - Murine acquired immunodeficiency syndrome (MAIDS) induced by defective LP-BM5
      murine leukemia virus is a disease with many similarities to human AIDS. Previous
      studies indicated that the depressed hematopoiesis observed in LP-BM5-infected
      marrow cultures may be attributable to a defect of hematopoietic stroma. We
      report here the generation of permanent stromal cell lines from noninfected and
      LP-BM5-infected marrow cultures. Retrovirus infection was confirmed by polymerase
      chain reaction for viral genome. The ability of these cell lines to support in
      vitro hematopoiesis was studied. Results indicated that, when cocultured with
      normal or infected nonadherent mononuclear cells, noninfected cell lines
      efficiently supported the production of hematopoietic precursors, whereas viral
      infected cell lines induced suppression of both normal and viral-infected
      progenitors. Expression of cytokine genes in stromal cell lines was also
      examined. All cell lines expressed equivalent levels of transcripts for stem cell
      factor and tumor necrosis factor alpha. However, infection was associated with
      higher levels of interleukin-4 and transforming growth factor beta 1 transcript
      expression. These findings suggest that infected stromal cell lines exhibit a
      defective hematopoietic microenvironment that produced altered cytokine
      expression resulting in faulty hematopoiesis. Further characterization of the
      defective cell lines should prove valuable for studies of the pathogenesis of
      murine AIDS.

PMID- 7520776
TI  - Interleukin-4 inhibits the expression of Kit and tryptase during stem cell factor
      dependent development of human mast cells from fetal liver cells.
AB  - Although interleukin-4 (IL-4) in mice is known to augment the proliferation of
      mast cells and to modulate the expression of certain mast cell protease
      transcripts, its effect on human mast cells is less well understood. The current
      study examined the effects of recombinant human IL-4 (rhuIL-4) on stem cell
      factor (SCF)-dependent fetal liver-derived human mast cells in liquid culture. In
      no case did rhuIL-4 augment proliferation of mast cells. rhuIL-4 selectively
      inhibited certain aspects of the development of mast cells in cultures of fetal
      liver cells with rhuSCF. These include lower numbers and percentages of cells
      expressing tryptase and surface Kit, smaller cells, and lower contents of cells
      for tryptase, histamine, and Kit. Development of metachromasia was not
      attenuated. The downregulation of Kit, the surface receptor for SCF, is probably
      a critical factor, because cells lacking this molecule would not be able to
      respond to SCF. In contrast to mast cell progenitors, mast cells already
      developed in vitro from fetal liver cells are relatively resistant to rhuIL-4,
      but are still dependent for survival on the presence of rhuSCF.

PMID- 7520777
TI  - Tumor necrosis factor-alpha (TNF-alpha) potently enhances in vitro macrophage
      production from primitive murine hematopoietic progenitor cells in combination
      with stem cell factor and interleukin-7: novel stimulatory role of p55 TNF
      receptors.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a bifunctional regulator of
      hematopoiesis, and its cellular responses are mediated by two distinct cell
      surface receptors. TNF-alpha generally inhibits the growth of primitive murine
      hematopoietic progenitor cells (Lin-Scal+) in response to multiple cytokine
      combinations, and the p75 TNF receptor is essential in signaling such inhibition.
      In the present study we show the reverse phenomenon in that TNF-alpha on the same
      progenitor cell population in combination with stem cell factor (SCF) and
      interleukin-7 (IL-7) through the p55 TNF receptor can recruit additional
      progenitors to proliferate. In contrast, TGF-beta 1, another bifunctional
      regulator of hematopoietic progenitor cell growth, completely blocked SCF plus IL
      7-induced proliferation. TNF-alpha increased the number of responding
      progenitors, as well as the size of the colonies formed. The synergistic effects
      of TNF-alpha were seen at the single cell level, suggesting that its effects are
      directly mediated. Finally, whereas SCF plus IL-7 promoted primarily
      granulopoiesis, the addition of TNF-alpha switched the differentiation toward the
      production of almost exclusively macrophages.

PMID- 7520778
TI  - The immunosuppressant rapamycin blocks in vitro responses to hematopoietic
      cytokines and inhibits recovering but not steady-state hematopoiesis in vivo.
AB  - The immunosuppressive drug rapamycin suppresses T-cell activation by impairing
      the T-cell response to lymphokines such as interleukin-2 (IL-2) and interleukin-4
      (IL-4). In addition, rapamycin blocks the proliferative response of cell lines to
      a variety of hematopoietic growth factors, including interleukin-3 (IL-3),
      interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), granulocyte
      macrophage-colony stimulating factor (GM-CSF), and kit ligand (KL), suggesting
      that it should be a strong inhibitor of hematopoiesis. In this report, we studied
      the effects of rapamycin on different hematopoietic cell populations in vitro and
      in vivo. In vitro, rapamycin inhibited the proliferation of primary bone marrow
      cells induced by IL-3, GM-CSF, KL, or a complex mixture of factors present in
      cell-conditioned media. Rapamycin also inhibited the multiplication of colony
      forming cells in suspension cultures containing IL-3 plus interleukin-1 (IL-1) or
      interleukin-11 (IL-11) plus KL. In vivo, treatment for 10 to 28 days with high
      doses of rapamycin (50 mg/kg/d, orally) had no effect on myelopoiesis in normal
      mice, as measured by bone marrow cellularity, proliferative capacity, and number
      of colony-forming progenitors. In contrast, the same treatment strongly
      suppressed the hematopoietic recovery normally seen 10 days after an injection of
      5-fluorouracil (5-FU; 150 mg/kg, intravenously [i.v.]). Thus, rapamycin may be
      detrimental in myelocompromised individuals. In addition, the results suggest
      that the rapamycin-sensitive cytokine-driven pathways are essential for
      hematopoietic recovery after myelodepression, but not for steady-state
      hematopoiesis.

PMID- 7520779
TI  - Activation of phosphatidylinositol-3 kinase by ligation of the interleukin-7
      receptor is dependent on protein tyrosine kinase activity.
AB  - Ligation of the interleukin-7 receptor (IL-7R) results in a rapid phosphorylation
      of tyrosine residues on multiple substrates. In addition, we have recently shown
      that the IL-7R mediates activation of phosphatidylinositol-3 (PI-3) kinase.
      Because PI-3 kinase activity can be immunoprecipitated with antiphosphotyrosine
      antibodies in most receptor systems studied, it has been examined that either PI
      3 kinase or an associated protein become tyrosine-phosphorylated after ligand
      binding. We studied here the possibility that PI-3 kinase, which is directly
      linked to mitogenic responses in growth factor receptors, is tyrosine
      phosphorylated after stimulation of the IL-7R. Using anti-p85 alpha or anti-p85
      beta antibodies raised against the p85 subunit of PI-3 kinase for
      immunoprecipitation and subsequent blotting with antiphosphotyrosine clearly
      shows that IL-7-stimulated human precursor cells contain both p85 alpha and p85
      beta proteins phosphorylated on tyrosine residues. Specific protein tyrosine
      kinase inhibitors such as tyrphostin AG-490 block total cell lysate
      phosphorylation and tyrosine phosphorylation on p85. Similar concentrations of
      this inhibitor also block in vitro and in vivo PI-3 kinase activity suggesting
      that this enzyme activation is dependent on the phosphorylation event of p85. In
      addition, AG-490 blocks IL-7-mediated proliferation in a dose-dependent manner,
      suggesting a link between the early events of PI-3 kinase phosphorylation and
      activation with IL-7R-induced cell growth.

PMID- 7520780
TI  - Human CD34+ fetal liver stem cells differentiate to T cells in a mouse thymic
      microenvironment.
AB  - Hematopoietic stem cells differentiate in the thymus to T cells along precisely
      defined intermediates. This process is thymic epithelium dependent and involves
      cytokines and cell-cell interactions between thymic stroma and T-cell precursors.
      Here we report that highly purified human CD34++ fetal liver stem cells
      differentiate to mature T cells, when seeded into isolated fetal thymic lobes of
      severe combined immunodeficient mice, and subsequently cultured in vitro. The
      human stem cells differentiate sequentially into CD4+CD8-CD3-, CD4+CD8+CD3-,
      CD4+CD8+CD3+, and finally, CD4+CD8-CD3+4 and CD4-CD8+CD3++ cells. Phenotypic
      analysis for additional maturation markers showed that these CD4 and CD8 single
      positive thymocytes are fully maturate cells. By immunochemistry, human HLA-DR+
      cells with a dendritic morphology could be detected. This novel chimeric human
      mouse fetal thymus organ culture offers a tool to study human T-cell ontogeny in
      vitro and is a rapid and reliable test method for T-cell precursor activity of
      cultured or transfected human stem cells.

PMID- 7520781
TI  - Developmental regulation of human gamma- and beta-globin genes in the absence of
      the locus control region.
AB  - Two lines of transgenic mice carrying a normal 40-kb Kpn I beta-globin cluster
      transgene lacking the locus control region (LCR) were analyzed for the expression
      of human gamma- and beta-globin genes during mouse development. After RNase
      protection assays, the ratios of human G gamma-, A gamma-, or beta-mRNAs relative
      to endogenous mouse zeta + alpha mRNAs were obtained for each stage of
      development. The two gamma transgenes were expressed in day-11.5 blood (embryonic
      stage) and day-13.5 blood (early fetal stage), but their expression was markedly
      decreased by day 16.5 of fetal life. Expression of the beta transgene was
      essentially absent at day 13.5, appeared at a low level by day 16.5, and was
      maximal by day 18.5, reaching a level similar to that observed in adult mice.
      Therefore, developmentally regulated expression of the human gamma- and beta
      globin transgenes was obtained in the absence of the LCR. The relative expression
      of human gamma- and beta-globin genes was also examined in mice carrying 40-kb
      Kpn I beta-cluster transgenes with two different base substitutions associated
      with nondeletion forms of hereditary persistence of fetal hemoglobin (HPFH), -202
      C-->G G gamma HPFH and -117 G-->A A gamma HPFH. The ratio of G gamma- to beta
      globin transcripts was markedly increased in red blood cells of adult mice from
      three different lines carrying the transgene with the -202 G gamma HPFH mutation.
      This result confirms our previous preliminary results (Tanaka et al: Ann NY Acad
      Sci, 612:167, 1990) indicating that the -202 G gamma HPFH phenotype was
      reproduced in transgenic mice. The relatively low levels of G gamma-mRNA
      expression in adult mice carrying the non-HPFH transgene excludes a major
      influence of the 3' beta-globin enhancer, present upstream of the G gamma gene
      because of the tandem repeat insertion, as a factor in the persistent G gamma
      gene expression observed in blood of adult mice carrying the -202 G gamma HPFH
      transgene. This conclusion is also supported by the fact that, in mice carrying
      the -117 A gamma HPFH transgene, G gamma-globin mRNA was detected in blood of
      adult animals only at low levels similar to that observed in the non-HPFH lines.
      However, the A gamma-HPFH phenotype was not reproduced in the transgenic lines
      carrying the -117A gamma HPFH mice.

PMID- 7520782
TI  - Granulocyte colony-stimulating factor after allogeneic bone marrow
      transplantation.
AB  - Hematopoietic growth factors have been shown to be effective in reducing the
      period of neutropenia after autologous bone marrow transplantation (BMT). Initial
      concerns over potential aggravation of graft-versus-host disease (GVHD) and
      increase in the incidence of relapse in patients with myeloid leukemias
      influenced the number of studies using hematopoietic growth factors after
      allogeneic BMT. We report the experience with 50 patients treated at a single
      institution using granulocyte colony-stimulating factor (G-CSF) after allogeneic
      sibling (n = 30) and matched unrelated (n = 20) BMT. The time to an absolute
      neutrophil count > or = 500/microL was significantly faster in patients who
      received G-CSF and cyclosporine and prednisone for GVHD prophylaxis when compared
      with historical control patients receiving the same GVHD prophylaxis (10 v 13
      days, P < .01). A similar accelerated myeloid engraftment was observed for those
      patients who received the addition of methotrexate for GVHD prophylaxis when
      compared with historical control patients receiving the same GVHD prophylaxis
      regimen (16 v 19 days, P < .05). The median time to engraftment for patients
      receiving a matched unrelated BMT and G-CSF was 17 days (range 13 to 26). We did
      not observe any increase in GVHD or early mortality in the matched related
      sibling BMT. The incidence of acute GVHD in the matched unrelated BMT recipients
      was also low at 21%; however, 9 patients (45%) died within 100 days of the date
      of BMT, similar to the experience reported with granulocyte-macrophage CSF. This
      study confirms the efficacy of G-CSF in accelerating myeloid engraftment after
      allogeneic matched sibling BMT. The higher early mortality associated with
      patients receiving matched unrelated BMT suggests that randomized controlled
      trials using G-CSF after allogeneic BMT should be performed.

PMID- 7520783
TI  - Granulocyte colony-stimulating factor and erythropoietin for the anemia of
      myelodysplastic syndromes: a real improvement with respect to erythropoietin
      alone?

PMID- 7520784
TI  - Increased fetal hemoglobin production in patients receiving valproic acid for
      epilepsy.

PMID- 7520785
TI  - Site-directed mutagenesis of HIV reverse transcriptase to probe enzyme
      processivity and drug binding.
AB  - Site-directed mutagenesis has demonstrated that changes within the human
      immunodeficiency virus reverse transcriptase coding sequence alone can account
      for viral resistance to inhibitors. Inhibitor sensitivity of mutant enzymes in
      vitro correlates with the sensitivity of the virus to non-nucleoside inhibitors
      observed in vivo, but this is not the case with nucleoside analogs. Recent
      structural, kinetic, and site-directed mutagenesis studies demonstrate the
      importance of enzyme-nucleic acid contacts in determining enzyme sensitivity to
      inhibitors in vitro, as well as how accurately the reverse transcriptase
      synthesizes DNA.

PMID- 7520786
TI  - Possible correlation of b3-a2-type bcr-abl messenger RNA defined by
      semiquantitative RT-PCR to platelet and megakaryocyte counts in Philadelphia
      positive chronic myelogenous leukemia.
AB  - Thirty-five patients with Philadelphia chromosome (Ph1)-positive chronic
      myelogenous leukemia (CML) were classified on the basis of the fusion pattern of
      bcr-abl mRNA determined by the reverse-transcriptase-polymerase chain reaction
      (RT-PCR) method. Semiquantitative assay of the bcr exon 2/abl exon 2 fused mRNA
      (b2-a2) and bcr exon 3/abl exon 2 fused mRNA (b3-a2) resulted in 21 patients
      showing b3-a2 type mRNA, seven showing b2-a2 type and seven showing coexpression.
      Quantification of the autoradiographic signals of amplified products was
      estimated using an MCID image analysis system. The relative intensity was defined
      as the ratio of bcr-abl signal to that of beta-actin. The relationship between
      the semiquantified bcr-abl mRNA and the platelet/megakaryocyte counts was
      analyzed. A possible correlation was found between the semiquantified b3-a2 type
      mRNA and the platelet (p < .05, N = 28) and megakaryocyte (p < .05, N = 13)
      counts of these patients. This finding suggests the possibility that b3-a2 mRNA
      may affect the thrombopoietic activity in Ph1-positive CML in a dose-response
      manner.

PMID- 7520787
TI  - Emphysematous pyelonephritis successfully treated with nephrectomy and
      granulocyte colony-stimulating factor.
AB  - A 58-year-old woman developed diabetic ketoacidosis and emphysematous
      pyelonephritis caused by Escherichia coli. She was successfully treated with
      nephrectomy, antibiotics, and recombinant human granulocyte colony-stimulating
      factor (rhG-CSF). RhG-CSF therapy may be an effective adjunct for diabetic
      patients with severe infection, even when neutropenia is not present.

PMID- 7520788
TI  - A potential role for nitric oxide in myocardial stunning.
AB  - Nitric oxide (NO) production by the human heart has been demonstrated in patients
      undergoing cardiac surgery. Similar to what has been described in other species,
      a basal production of NO by the human heart is seen (126 +/- 42 pmol/min per
      gram). Following reperfusion, at the end of the procedure, the level of NO
      production increases significantly reaching concentrations of 1430 +/- 330
      pmol/min per gram. Increased activity for the enzyme NO synthase (NOS) (8.0 +/-
      1.2 pmol/mg prebypass vs 26.4 +/- 4.8 pmol/mg postbypass) coincides with changes
      in NO production and occurs at a time when myocardial stunning is clinically
      detectable. The significance of these findings is discussed and suggest a role
      for NO in the pathophysiology of myocardial stunning.

PMID- 7520789
TI  - Expression of E-selectin on coronary endothelium after myocardial ischemia and
      reperfusion.
AB  - Neutrophils localize in ischemic or infarcted myocardium and thus are implicated
      in playing a role in myocardial reperfusion injury and stunning. We studied one
      of the mechanisms by which neutrophils are recruited into the region of ischemic
      myocardium. Anesthetized adult rhesus monkeys (n = 2) underwent ligation of one
      of the obtuse marginal coronary arteries for 90 minutes followed by 5 hours of
      reperfusion. Tissues from the normal perfused area of the heart and from the
      ischemic area were preserved in methacarn fixative after sacrificing the animal
      at the end of the reperfusion period. Immunohistochemical staining showed that E
      selectin is not constitutively expressed on coronary endothelium in vivo. E
      selectin, however, was upregulated in selective endothelial cells located in the
      postcapillary coronary venules in response to ischemia and reperfusion. The
      presence of E-selectin in this setting suggests that it may have a similar role
      as in the recruitment of neutrophils into other inflamed or damaged tissues.

PMID- 7520790
TI  - Dispersion of chlorpyrifos in soil beneath concrete slabs.

PMID- 7520791
TI  - Improvement in blastocyst hatching of mouse embryos cocultured with human
      placental cells.
AB  - PURPOSE: Although the hatching of embryos is an important phenomenon, the
      mechanism of hatching remains controversial. Therefore, we attempted to develop a
      new coculture system with human placental cells to investigate the hatching of
      mouse embryos. RESULTS: In our new system there was no difference in development
      from the two-cell stage to blastocysts between embryos cultured with a T6 medium
      and embryos cocultured with human placental cells at 1 x 10(5), 5 x 10(5), and 1
      x 10(6) cells/ml. However, the hatching-rate cell number increased significantly
      in embryos cocultured with placental cells compared to embryos cultured without
      placental cells. [3H]Thymidine uptake did not show any significant difference
      from the beginning of in vitro culture to the hatching stage between the
      coculture group and the control group. Nevertheless, the [3H]uridine uptake was
      significantly different in the two groups, measuring 2167 +/- 532 cpm/10 embryos
      in the coculture group and 804 +/- 86 cpm/10 embryos in the control group at 114
      hr after human chorionic gonadotropin injection (P < 0.01). CONCLUSION: These
      results therefore seem to indicate that the hatching of blastocysts depends on
      the protein synthesis of the embryos and not on DNA duplications.

PMID- 7520792
TI  - Relationship of calcitonin mRNA expression to the differentiation state of HL 60
      cells.
AB  - Raised plasma levels of immunoreactive human calcitonin (ihCT) can be found in
      patients with myeloid leukemia and seem to indicate a poor prognosis. High levels
      were found in acute undifferentiated and acute myeloblastic leukemia. To test
      whether CT expression could be a marker of myeloid differentiation, we used the
      promyelocytic leukemia cell line HL 60 which also expresses ihCT as a model
      system for myeloid differentiation. Exponentially growing HL 60 cells as well as
      differentiation induced HL 60 cells expressed a single 1.0 Kb CT transcript. The
      induction of HL 60 cell differentiation along the granulocytic lineage by DMSO or
      HMBA had no effect on the level of CT transcripts. Induction of
      monocytic/macrophagic differentiation by TPA resulted in a transient, about 10
      fold elevated expression of CT steady state mRNA after 24 h. In contrast to TPA,
      induction of HL 60 cell differentiation along the monocytic pathway by Vit D3 had
      no detectable effect on the level of the CT in RNA expression at corresponding
      time points. These findings suggest that the transient induction of CT steady
      state mRNA expression by TPA is rather a direct effect of the phorbol ester than
      commitment along the monocytic line of differentiation.

PMID- 7520793
TI  - Richter's syndrome showing pronounced lymphadenopathy in response to
      administration of granulocyte colony-stimulating factor.
AB  - A patient with Richter's syndrome developed rapid generalized lymph node
      enlargement with a decrease of peripheral blood lymphocytes after recombinant
      human granulocyte colony-stimulating factor (rhG-CSF) therapy for neutropenia
      induced by chemotherapy. The lymphadenopathy subsided spontaneously following
      discontinuation of rhG-CSF medication. Reinstitution of rhG-CSF therapy was
      followed by the same response as during initial therapy. Histopathologically, the
      lesions were characteristic of diffuse large cell lymphoma (DLL) with no evidence
      of myeloid cell involvement. No spontaneous contraction of enlarged lymph nodes
      followed withdrawal of the second course, but the enlargement subsided with
      chemotherapy. The patient died of myocardial infarction. All residual tumors
      examined post mortem presented microscopic features of small lymphocytic lymphoma
      (SLL), and G-CSF receptor was demonstrated on these neoplastic cells by Northern
      blot hybridization analysis. This observation indicates that some B cell
      malignancies may retain G-CSF receptor and respond to G-CSF.

PMID- 7520795
TI  - Harmonic and anharmonic aspects in the dynamics of BPTI: a normal mode analysis
      and principal component analysis.
AB  - A comparison is made between a 200-ps molecular dynamics simulation in vacuum and
      a normal mode analysis on the protein bovine pancreatic trypsin inhibitor (BPTI)
      in order to elucidate the dual aspects of harmonicity and anharmonicity in the
      dynamics of proteins. The molecular dynamics trajectory is analyzed using
      principal component analysis, an effective harmonic analysis suited for
      comparison with the results from the normal mode analysis. The results suggest
      that the first principal component shows qualitatively different behavior from
      higher principal components and is associated with apparent barrier crossing
      events on an anharmonic conformational energy surface. The higher principal
      components appear to have probability distributions that are well approximated by
      Gaussians, indicating harmonicity. Eliminating the contribution from the first
      principal component reveals a great deal of correspondence between the 2 methods.
      This correspondence, however, involves a factor of 2, as the variances of the
      distribution of the higher principal components are, on average, roughly twice
      those found from the normal mode analysis. A model is proposed to reconcile these
      results with those from previous analyses.

PMID- 7520794
TI  - Receptor binding properties of four-helix-bundle growth factors deduced from
      electrostatic analysis.
AB  - Hormones of the hematopoietin class mediate signal transduction by binding to
      specific transmembrane receptors. Structural data show that the human growth
      hormone (hGH) forms a complex with a homodimeric receptor and that hGH is a
      member of a class of hematopoietins possessing an antiparallel 4-alpha-helix
      bundle fold. Mutagenesis experiments suggest that electrostatic interactions may
      have an important influence on hormone-receptor recognition. In order to examine
      the specificity of hormone-receptor complexation, an analysis was made of the
      electrostatic potentials of hGH, interleukin-2 (IL-2), interleukin-4 (IL-4),
      granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony
      stimulating factor (GM-CSF), and the hGH and IL-4 receptors. The binding surfaces
      of hGH and its receptor, and of IL-4 and its receptor, show complementary
      electrostatic potentials. The potentials of the hGH and its receptor display
      approximately 2-fold rotational symmetry because the receptor subunits are
      identical. In contrast, the potentials of GM-CSF and IL-2 lack such symmetry,
      consistent with their known high affinity for hetero-oligomeric receptors.
      Analysis of the electrostatic potentials supports a recently proposed hetero
      oligomeric model for a high-affinity IL-4 receptor and suggests a possible new
      receptor binding mode for G-CSF; it also provides valuable information for
      guiding structural and mutagenesis studies of signal-transducing proteins and
      their receptors.

PMID- 7520796
TI  - Continuous epitopes of human lymphotoxin and their topographies.
AB  - Human lymphotoxin (hLT or TNF-beta) is a lymphokine that is structurally and
      functionally related to tumor necrosis factor alpha (TNF-alpha). The continuous
      epitopes of hLT were located by examining the cross-reaction between rabbit anti
      hLT antibody and peptides derived from proteolytic digestion and chemical
      synthesis. Three antigenic sites, corresponding to residues 40-48, 83-94 and 139
      147, of the protein sequence, were located by this approach. Since residues 49-57
      also exhibited trace antigenicity, but residues 45-52 displayed no reaction, the
      whole peptide fragment consisting of residues 40-57 might be necessary for
      antigenicity. A comparison of the antigenic determinants with the loop structures
      obtained from X-ray crystallographic studies of hLT showed that all of the
      epitopes are found on or adjacent to functionally important domains.

PMID- 7520797
TI  - CFTR haplotype backgrounds on normal and mutant CFTR genes.
AB  - Ten polymorphic loci, located in a 1 Mb interval across the cystic fibrosis
      locus, were analyzed on normal and mutant CFTR genes. A different distribution of
      haplotype backgrounds among normal and mutant CFTR genes was observed. With
      exception of the D7S8 locus, the three most common mutations, delta F508, G542X
      and N1303K, were found on an identical haplotype background. In agreement with
      the observed linkage equilibrium between the Q1463Q and D7S8 loci, both alleles
      at the D7S8 locus were found on delta F508 CFTR genes. However, the G542X and
      N1303K mutations, which have been estimated to be at least 35000 years old, were
      found to be associated with a single allele at the D7S8 locus. Absence of
      recombination between the D7S8 and Q1463Q loci was also observed on normal CFTR
      genes with this haplotype background. At the Tn locus in intron 8, allele 9 known
      to result in very efficient splicing was associated with the most frequent
      mutations. At the M470V locus, located in a conserved region of the first
      nucleotide binding fold, the amino acid methionine was found to be associated
      with the frequent mutations, in particular with mutations located in one of the
      two nucleotide binding folds which are generally known as severe mutations with
      regard to exocrine pancreatic function. On mutant CFTR gene, this locus was in
      complete association with the centromeric D9 locus, in the absence of a complete
      association with the intervening loci.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520798
TI  - Two novel mutations in the CFTR gene: W1089X in exon 17B and 4010delTATT in exon
      21.

PMID- 7520799
TI  - Homozygosity for a novel missense mutation (I175V) in exon 5 of the CFTR gene in
      a family of Armenian descent.

PMID- 7520800
TI  - Characterization of the Spodoptera frugiperda TATA-binding protein: nucleotide
      sequence and response to baculovirus infection.
AB  - A cDNA clone containing a 921 bp open-reading frame (307 amino acids; 34 kDa)
      homologous to the TATA-binding protein (TBP) was isolated and sequenced from a
      Spodoptera frugiperda cell line that is commonly used in the baculovirus
      expression system. Analysis of the S. frugiperda TBP (SfTBP) sequence showed that
      the amino-terminal portion of SfTBP diverged significantly from that of other TBP
      sequences including Drosophila melanogaster whereas the carboxy-terminal sequence
      was highly conserved. Southern blot analysis indicated that SfTBP was encoded by
      a single gene in the S. frugiperda genome. Northern blot analysis indicated that
      steady-state levels of the 1.3 kb SfTBP transcript declined by 24 h post
      infection corresponding to the time of virus-induced inhibition of host-cell
      transcription. Corresponding western blot analysis showed that TBP protein levels
      remain constant up to 72 h post-infection.

PMID- 7520801
TI  - Protein ubiquitination in the posterior silk glands of Bombyx mori.
AB  - Ubiquitin gene expression and the ubiquitination of proteins in the posterior
      silk glands (PSG) of B. mori were analyzed developmentally with respect to
      fibroin synthesis and degeneration. Two ubiquitin transcripts are expressed
      throughout larval stages, and the level of each transcript is regulated
      differently. The larger transcript, a polyubiquitin mRNA, was abundant during the
      molt stage, while levels of the smaller ubiquitin transcript increased
      immediately after molting. Only a single 65 kDa ubiquitinated protein was
      detected late in the 5th instar, and the amount increased up to spinning stage.
      This ubiquitinated protein may participate in the PSG degeneration.

PMID- 7520802
TI  - Selective rubella vaccination programmes: a survey of districts in England and
      Wales.
AB  - A survey of district immunisation coordinators in the 183 health districts of
      England and Wales was carried out to assess the implementation of selective
      rubella vaccination programmes. The survey showed that school health services
      vaccinate schoolgirls against rubella in 161 (93%) of the 173 districts whose
      immunisation coordinators responded. The accuracy of data on vaccination coverage
      of schoolgirls is limited because districts interpret the numerator and
      denominator required by the Department of Health in different ways. Districts
      have also experienced problems in monitoring the uptake of vaccination through
      general practitioners. Comprehensive antenatal screening programmes for rubella
      immunity operate in 164 districts (95%), but few districts are auditing the
      postpartum vaccination of seronegative women. If child health computer records
      were maintained and updated until children left school, it would be possible to
      produce reliable data on the percentage of girls who had been vaccinated against
      rubella by the age of 14.

PMID- 7520803
TI  - The immunisation coordinator: improving uptake of childhood immunisation.
AB  - Attention to local uptake of childhood immunisation is fundamental to the
      achievement of national targets. The aim of this investigation was to discover
      whether local interventions by the immunisation coordinator in a district health
      authority improved uptake. The immunisation coordinator and a public health nurse
      determined the immunisation uptake in their locality. They made inquiries, and
      responded to general practitioners and health visitors who asked them to help
      encourage persistent non-attenders to consent to immunisation. All interventions
      intended to encourage parents to consent to immunisation (such as telephone
      calls, letters, and home visits), and their outcomes, were monitored. The uptake
      of immunisation was remeasured after one year. Ninety-three children were
      identified whose parents had not responded to repeated invitations for
      immunisation. Eleven cases were lost to follow up: the families of 10 children
      had moved out of the area, and one child had died. The remaining 82 children
      could be divided into two groups: one group, of 49 children, was due for primary
      vaccination (diphtheria, tetanus, pertussis, and polio, and measles, mumps, and
      rubella), and a second group, of 33 children, was due for the preschool
      (diphtheria, tetanus, and polio) booster. Fifty-eight of the 82 children were
      vaccinated as a result of the intervention. All but two general practices
      achieved the 90% target for uptake. The review showed that the locality as a
      whole achieved greater vaccine coverage. The biggest improvement was in the
      preschool booster uptake, which rose from 87% to 90%.

PMID- 7520804
TI  - COVER (cover of vaccination evaluated rapidly): 30.

PMID- 7520805
TI  - Cutaneous diphtheria in Bristol.

PMID- 7520806
TI  - Salmonella virchow phage type 26.

PMID- 7520807
TI  - Comparison of the effects of commonly used wound agents on epithelialization and
      neovascularization.
AB  - BACKGROUND: The primary effect sought with most topical wound therapy is
      antimicrobial. Topical wound agents are thought to promote normal healing by
      protecting the wound from infection. In this study, we examined the effect of six
      commonly used topical wound agents (bacitracin, sodium hypochlorite, silver
      nitrate, silver sulfadiazine, mafenide acetate, and povidone-iodine) on
      epithelialization and neovascularization in noninfected wounds. For this study, a
      new wound model was used in which direct visualization and quantification of
      wound epithelialization and neovascularization were carried out throughout the
      entire healing process. STUDY DESIGN: We measured the effect which 500 U per g of
      bacitracin, 0.25 percent of sodium hypochlorite, 0.5 percent silver nitrate, 1
      percent silver sulfadiazine, 8.5 percent mafenide acetate, and 10 percent
      povodione-iodine had on the rate of wound epithelialization and
      neovascularization. The agents were applied topically to 99 circular full
      thickness wounds (2.25 mm diameter, 0.125 mm depth) created on the dorsum of male
      hairless mouse ears. This model enabled us to visualize and measure directly
      wound epithelialization and neovascularization repeatedly throughout healing,
      using intravital video microscopy and computerized digitized planimetry. RESULTS:
      Control wounds and wounds treated with silver sulfadiazine (n = 18) and mafenide
      acetate (n = 14) epithelialized in 7.2 +/- 0.7, 7.1 +/- 0.3, and 7.3 +/- 0.3
      days, respectively. This was significantly (p < 0.01) faster than the wounds
      treated with povidone-iodine (n = 10), sodium hypochlorite, (n = 8), and
      bacitracin (n = 13). Wounds treated with povidone-iodine epithelialized the
      slowest (11.8 +/- 0.55 days). Wound neovascularization was completed most rapidly
      in the groups treated with povidone-iodine and silver sulfadiazine (15.0 +/- 0.4
      and 15.3 +/- 0.7 days, respectively). This was significantly (p < 0.05) faster
      than wounds treated with silver nitrate (n = 15), which neovascularized in 18.4
      +/- 0.56 days. One-half of the wounds treated with sodium hypochlorite (eight of
      16) did not epithelialize or neovascularize. CONCLUSIONS: The various
      antimicrobial agents studied in our in vivo model affect wound epithelialization
      and neovascularization differently. These effects on these two very important
      aspects of healing should be taken into consideration when indicating a specific
      agent for treatment of different types of wounds.

PMID- 7520808
TI  - Granulocyte-colony stimulating factor (G-CSF) production of human fibroblasts
      (KMST-6/RAS line) transformed with 60Co gamma rays and c-Ha-ras oncogene.

PMID- 7520809
TI  - Fibroblasts isolated from human pterygia exhibit transformed cell
      characteristics.
AB  - Pterygium is a degenerative corneal limbal process and UV irradiation has been
      suggested as being a major environmental predisposing factor. The invasive nature
      of the fibroblasts associated with pterygia raises the question as to whether
      these cells are transformed. To test this hypothesis, we established fibroblast
      strains from autologous and heterologous pterygial and conjunctival specimens,
      respectively, from subjects between 40 to 50 yr of age, and compared their growth
      characteristics in culture. All pterygial fibroblast strains exhibited a reduced
      dependence on serum and exogenous growth factors for growth and reached a
      saturation population density that was threefold higher than conjunctival
      fibroblasts cultured under the same conditions. In addition, all pterygial
      fibroblast strains were able to form colonies in soft agar in 5% fetal bovine
      serum at a 6.0 to 7.5% efficiency. Under the same experimental conditions, none
      of the conjunctival fibroblast strains were able to grow. The results presented
      support the conclusion that pterygial fibroblasts have acquired many of the
      properties of the transformed phenotype.

PMID- 7520810
TI  - Culture of bovine thoracic duct endothelial cells.

PMID- 7520811
TI  - Non-hormonal factors on differentiation of bovine mammary cells.

PMID- 7520812
TI  - In vitro modulation of filament bundling in F-actin and keratins by annexin II
      and calcium.
AB  - In our preliminary subcellular localization experiment we demonstrated that
      annexin II co-localized with submembranous actin in subpopulations of both
      cultured fibroblasts and keratinocytes. To investigate the physical interaction
      between annexin II and actin at the cell periphery, in vitro reconstitution
      experiments were carried out with keratins used as a control. Annexin II,
      isolated by immunoaffinity column chromatography, was found to exist as globular
      structures measuring 10 to 25 nm in diameter by rotary shadowing, similar to a
      previous report. We believe that these structures represent its polymeric forms.
      By negative staining, monomeric annexin II was detectable as tapered rods,
      measuring 6 nm in length and 1 to 2 nm in diameter. When annexin II was mixed
      with actin in 3 mM piperazine-N, N-bis-2-ethanesulfonic acid (PIPES) buffer with
      10 mM NaCl2, 2 mM MgCl2 and 0.1 mM CaCl2, thick twisting actin bundles formed,
      confirming previous reports. This bundling was much reduced when calcium was
      removed. In the presence of 5 mM ethylenediamine tetra-acetic acid (EDTA) in 5 mM
      tris, pH 7.2, keratins were found to form a network of filaments, which began to
      disassemble when the chelator was removed and became fragmented when 0.1 mM CaCl2
      was added. Keratins under the same conditions did not fragment when annexin II
      was present. These results suggest that annexin II, in conjunction with Ca2+, may
      be involved in a flexible system accommodating changes in the membrane
      cytoskeletal framework at the cell periphery in keratinocytes.

PMID- 7520813
TI  - Differential replication of heterochromatin in polytene chromosomes of the Old
      World screw-worm fly, Chrysomya bezziana (Diptera: Calliphoridae), analysed by
      fluorescence staining.
AB  - The distribution and replication of heterochromatin in polytene trichogen
      chromosomes of the Old World screw-worm fly, Chrysomya bezziana, were studied
      using fluorescent staining techniques. Quinacrine and distamycin-DAPI, which
      selectively stain AT-rich DNA, and chromomycin, specific for GC-rich sequences,
      were used. Bright quinacrine and DA-DAPI fluorescence was found in the sex
      chromosome body and in all autosomal centromere regions. Chromomycin (CMA)
      staining results in very little bright fluorescence of the sex chromosome body
      and autosomal centromeric regions, but many bright bands of varying morphology
      are distributed in autosomal arms. The expected negative CMA staining of
      quinacrine and DA-DAPI bright regions was not found. The lack of reciprocal
      staining patterns may result from changes in the higher order chromatin structure
      of polytene chromosomes, or intercalation of divergent heterochromatic sequences.
      Comparison of the different staining techniques in mitotic and polytene cells
      shows that heterochromatin is differentially under-replicated, so that the
      proportions of the distinct fluorescent-specific chromatin changes during
      polytenization. CMA staining within autosomal arms suggests that repeated
      sequences intercalated in euchromatin are co-replicated during polytenization.
      The numerous fluorescent markers described also provide further morphological
      features for use in comparative cytological analysis of C. bezziana.

PMID- 7520814
TI  - Comparison of the 13C relaxation times and proton scalar couplings of BPTI with
      values predicted by molecular dynamics.
AB  - The experimental carbon-13 relaxation times of BPTI have been compared with the
      values predicted by molecular-dynamics simulations. Since the carbon-13 T1 values
      are sensitive monitors of the rates and amplitudes of the internal motions of the
      protein, this comparison was made to test the extent to which molecular dynamics
      provides an accurate depiction of the internal motions of proteins. The
      experimental and predicted amide-alpha scalar couplings were also compared, since
      this coupling is dependent on the conformation of the protein. These comparisons
      have shown that the molecular-dynamics simulation predicts results that are in
      good overall agreement with the experimental data.

PMID- 7520815
TI  - Characterization of FcR Ig-binding sites and epitope mapping.
AB  - The low-affinity receptor for IgG, Fc gamma RII, and the high-affinity receptor
      for IgE, Fc epsilon RI, are functionally distinct but structurally homologous
      receptors. These characteristics have been exploited using a chimeric receptor
      strategy to examine segments of human Fc gamma RII for IgG-binding function. A
      series of chimeric receptors was generated by exchanging coding regions of the
      extracellular ligand-binding regions between Fc gamma RII and the Fc epsilon RI
      alpha chain using splice overlap extension by the polymerase chain reaction. The
      expression of these chimeric receptors in COS-7 cells and analysis of their
      IgG/IgE binding capacities have enabled the Ig-binding region of Fc gamma RII to
      be localized to a subregion of the second extracellular domain. The localization
      of the Ig-binding region of Fc gamma RII has provided the opportunity of
      performing site-directed mutagenesis to determine the key amino acids involved in
      the interaction of the receptor with IgG. These findings demonstrate that the
      chimeric receptor approach is a powerful technique for the dissection of
      structure/function relationships of structurally related yet functionally
      different molecules.

PMID- 7520816
TI  - Application of immunogold labelling for light and electron microscopic
      localization of endothelial leukocyte adhesion molecule 1 (ELAM-1) on cultured
      human endothelial cells.
AB  - This study describes the expression characteristics of E-selectin molecules using
      immunogold histochemical techniques on cultured human umbilical vein endothelial
      cells (HUVEC). The expression of E-selectin was induced by tumour necrosis factor
      alpha (TNF-alpha, 300 U/ml), phorbol ester (PMA, 10 ng/ml) and bacterial
      lipopolysaccharide (LPS, 4 micrograms/ml). No expression was demonstrated on
      control cells. Using the silver-enhanced colloidal gold-labelling technique, at
      the light microscopical level, HUVEC could be distinctively subdivided into three
      staining types. The cell labelling index, expressed as the number of 'positively'
      stained cells as a proportion of all viewed cells was the highest in the LPS
      group. For transmission electron microscopy (TEM) the preembedding
      immunocytochemical staining method and embedding in epoxy resin (Agar 100)
      according to standard procedures was used. In TEM gold particles were localized
      in close association with the apical plasma membrane, as well as on the surface
      of microvillus-like projections (the latter by TNF-alpha group). For high
      resolution scanning electron microscopy (HR-SEM) the secondary (SEI) and the
      backscattered electron imaging (BEI) modes were used. Gold particles were
      randomly distributed over the whole cell surface, although they appeared to be
      denser in the perinuclear zone. The quantitative evaluation on SE and BE viewing
      (the number of gold particles per cell area in microns 2) demonstrated the
      highest density of labelling in the LPS-treated group, but there was only a
      significant difference between LPS and TNF-alpha groups (P < 0.01, t-test).
      Furthermore, the ultrastructural studies indicated that treatment with substances
      which up-regulate E-selectin expression was not related to toxic cell damage or
      significant alterations of cellular ultrastructure.

PMID- 7520817
TI  - Structural studies of the binding of the anti-ulcer drug sucrose octasulfate to
      acidic fibroblast growth factor.
AB  - BACKGROUND: The anti-ulcer drug sucrose octasulfate (SOS) binds to fibroblast
      growth factors (FGFs), proteins which stimulate the growth and differentiation of
      several cell types, including stomach epithelial cells. It is believed that SOS
      stabilizes FGFs against acid denaturation in the stomach, thus enhancing their
      ability to stimulate healing of ulcerated tissue. SOS binds to the same site on
      FGF as heparin and other proteoglycans; in vivo, FGF must bind to cell-surface
      proteoglycans or to heparin before it can interact with FGF receptors and
      stimulate growth. The details of this process are not understood. RESULTS: We
      report the crystal structure of a 1:1 complex between acidic FGF (aFGF) and SOS
      at 2.7 A resolution. SOS binds to a positively charged region of aFGF, largely
      composed of residues 112-127, and makes contacts primarily with Lys112, Arg116,
      Lys118, and Arg122. This region is also important in binding heparin. The overall
      conformation of aFGF is not changed by binding SOS, although the positions of
      some side chains in the binding site shift by as much as 6 A. CONCLUSION: The SOS
      FGF crystal structure is consistent with the model that SOS stabilizes FGF by
      neutralizing several positively charged residues that would destabilize the
      native structure by electrostatic repulsion. On the basis of this structure, we
      provide a model for the complex of heparin with an FGF dimer. Such interactions
      may facilitate FGF receptor dimerization, which may be important in receptor
      signaling.

PMID- 7520818
TI  - Lectins on a roll: the structure of E-selectin.
AB  - The crystal structure of the lectin/EGF portion of E-selectin confirms
      anticipated similarities with homologous domains, but reveals some surprising
      features that emphasize the limitations of homology modelling.

PMID- 7520819
TI  - Structure of a soluble, glycosylated form of the human complement regulatory
      protein CD59.
AB  - BACKGROUND: CD59 is a cell-surface glycoprotein that protects host cells from
      complement-mediated lysis by binding to and preventing the normal functioning of
      the complement proteins C8 and/or C9 which form part of a membrane penetrating
      assembly called the membrane attack complex. CD59 has no structural similarity to
      other complement proteins, but is an example of a plasma protein domain type
      found also in murine Ly-6 proteins and the urokinase-type plasminogen activator
      receptor. RESULTS: CD59 was purified from human urine, retaining the N-glycan and
      at least some of the non-lipid component of the glycosylphosphatidylinositol
      membrane anchor. The three-dimensional structure of the protein component has
      been determined in the presence of the carbohydrate groups using two-dimensional
      NMR spectroscopy. The protein structure is well defined by the NMR data (root
      mean square deviation from the mean structure of 0.65 A for backbone atoms and no
      distance constraint violations greater than 0.4 A). Structure calculations were
      also carried out to model the orientation of the N-acetylglucosamine residue that
      is directly linked to Asn18. CONCLUSIONS: The main features of the protein
      structure are two antiparallel beta-sheets (a central one with three strands and
      another with two), a short helix that packs against the three-stranded beta
      sheet, and a carboxy-terminal region that, although lacking regular secondary
      structure, is well defined and packs against the three-stranded beta-sheet, on
      the opposite face to the helix. We have used the structure, in combination with
      existing biochemical data, to identify residues that may be involved in C8
      binding.

PMID- 7520820
TI  - Human genomic diversity in Europe: a summary of recent research and prospects for
      the future.
AB  - Gene frequencies in Europe are intermediate with respect to those of other
      continents. A phylogenetic tree reconstructed from 95 gene frequencies tested on
      26 European samples shows some deviant populations (Lapps, Sardinians, Greeks,
      Yugoslavs, Basques, Icelanders and Finns) and other weakly structured
      populations. This behavior may have a simple interpretation: Europeans have not
      evolved according to a tree of descent probably because of the major role played
      by migrations in prehistorical and historical times. The leading component of the
      European genetic landscape is a gradient that originates in the Middle East and
      is directed to the northwest. According to the hypothesis by Ammerman and Cavalli
      Sforza this gradient was generated by a migration of Neolithic farmers from
      Anatolia followed by continuous, partial admixture of the expanding farmers with
      local hunter-gatherers. Other leading components of the gene frequencies in
      Europe show correlations with possible movements of Uralic-speaking people and
      pastoral nomads from a region north of the Caucasus and Black Sea, which
      according to Gimbutas is the area of origin of Indo-European speakers. This
      analysis is based on classical pre-DNA genetic markers. The prospect of future
      research using DNA polymorphisms is discussed in the context of the Human Genome
      Project.

PMID- 7520821
TI  - Identification of the Goodpasture antigen, alpha 3(IV) NC1, and four other NC1
      domains of type IV collagen, by amino-terminal sequence analysis of human
      glomerular basement membrane separated by two-dimensional electrophoresis.
AB  - Two-dimensional (2-D) electrophoresis of collagenase-digested human glomerular
      basement membrane (GBM), containing the Goodpasture antigen, revealed a range of
      monomeric (24-30 kD) and dimeric (43-56 kD) subunits present across a pI range of
      3-10. Five distinct alpha(IV)-chains were identified by amino-terminal sequence
      analysis of 18 of these components transferred to polyvinylidene difluoride
      membrane. The positions of the well-characterised 26-kD alpha 1(IV)-chain and 24
      kD alpha 2(IV)-chain were confirmed. A highly cationic 28-kD monomer was
      identified as the alpha 3(IV)-chain, while more neutral 28-kD monomers were found
      to contain the alpha 4(IV)-chain. Sequences from neutral 26-kD monomers
      corresponded to the known cDNA sequence of the alpha 5(IV)-chain. The presence of
      charge isoforms of the alpha 1(IV)- and alpha 4(IV)-chains was confirmed by
      identification of several monomers with different pI but the same sequence.
      Sequence analysis of dimeric components demonstrated homodimers of alpha 1(IV),
      alpha 2(IV) and alpha 4(IV), and suggested the presence of heterodimers of alpha
      3/alpha 5 and alpha 1/alpha 5. 2-D Western blots of human GBM, with anti-GBM
      autoantibodies, a monoclonal antibody (P1) to the Goodpasture antigen and a
      monoclonal antibody to the alpha 3(IV)-chain, demonstrated that the major
      autoantigenic epitope was localised to the alpha 3(IV)-chain, but that there was
      also reactivity with the alpha 4(IV)-chain.

PMID- 7520822
TI  - The trajectory of the sympathetic nerve fibers to the rat cochlea as revealed by
      anterograde and retrograde WGA-HRP tracing.
AB  - Wheat germ agglutinin-horseradish peroxidase conjugate was injected in the
      unilateral superior cervical ganglion (SCG), and the projection pathways of
      postganglionic sympathetic nerve fibers innervating the cochlea were traced in
      the rat. The labeled axons advanced along the internal carotid artery (ICA), and
      a few advanced caudally in the major petrosal nerve (MPN) and entered the facial
      nerve, while the majority ran rostral to the pterygopalatine ganglion at the
      point where they crossed the MPN in the carotid canal. The rest of the labeled
      fibers remained on the surface of the ICA and advanced to the cranial cavity.
      Most of the labeled fibers along the facial nerve joined the cochlear nerve and
      finally reached the osseous spiral lamina through the spiral ganglion. Some of
      the labeled fibers ran along the anterior inferior cerebellar artery from the
      basilar artery which was previously thought to have been the only pathway. We
      could not find any labeled fiber on the modiolar artery from anterior inferior
      cerebellar artery in the cochlea. These observations are consistent with our
      hypothesis that the sympathetic fibers innervating the neural tissues or related
      structures follow nerve fibers and meninges as matrices of projection pathways
      rather than arteries.

PMID- 7520823
TI  - Differential distribution of nitric oxide synthase in neural pathways to the
      urogenital organs (urethra, penis, urinary bladder) of the rat.
AB  - Axonal tracing techniques were used in combination with histochemical methods
      (NADPH-diaphorase activity and nitric oxide synthase immunoreactivity) to examine
      the distribution of nitric oxide synthase (NOS) in the neural pathways to the
      urogenital organs of the male rat. The major goal of this study was to compare
      the histochemical properties of the efferent and afferent neurons innervating the
      urethra with the properties of neurons innervating the penis and bladder. In the
      major pelvic ganglion (MPG) large percentages of postganglionic neurons
      innervating the urethra (44%) and the penis (97%) exhibited NADPH-diaphorase
      (NADPH-d) staining whereas only a small percentage (3.5%) of neurons innervating
      the bladder were N-d positive. Urethral neurons stained for N-d were on average
      smaller (33.3 microns diameter) than unstained neurons (54.5 microns diameter).
      The histochemical difference between the three types of neurons was also
      reflected in NOS-immunoreactivity (IR); however, the absolute percentage of
      neurons exhibiting NOS-IR was low: penis (21%), urethra (11%) and bladder (0%).
      Axonal varicosities staining for N-d or NOS-IR were noted in the MPG in close
      proximity to unidentified neurons and neurons innervating the urogenital organs.
      A considerable number of afferent neurons in the lumbosacral dorsal root ganglia
      (DRG) stained for N-d (64 cells/L6, 35 cells/S1 section); however, only small
      numbers of neurons (average 1 cell/section) exhibited NOS-IR. N-d activity was
      detected in a large percentage of urethral (55%) and bladder (80%) afferent
      neurons in the L6-S1 dorsal root ganglia (DRG) but in relatively few (12%) penile
      afferent neurons in the L6 ganglia. These results suggest that the contribution
      of nitric oxide (NO) to neurotransmission varies considerably in different
      urogenital organs. NO could have a significant role in postganglionic efferent
      pathways to the urethra and penis but very likely has no role in the efferent
      pathways to the bladder. Similarly, the prominence of N-d staining in some DRG
      neurons (e.g. urethra and bladder) but not others (penile) also raises the
      possibility of a varying role of NO in afferent pathways. However, in these
      neurons N-d staining was not paralleled by NOS-IR, which was present in only a
      small percentage of neurons. Thus, N-d staining may not reflect the presence of
      NO in afferent pathways to the pelvic viscera.

PMID- 7520824
TI  - Cytoplasmic Ca2+ activity regulation as measured by a calcium-activated current.
AB  - Calcium-activated non-selective cation (CAN) currents were activated by
      quantitative injections of Ca2+ into voltage clamped bursting neurons of the
      snails Helix aspersa or Helix pomatia. Membrane potential was held at the
      potassium equilibrium potential and CAN currents were fit with a rising and
      falling exponential function. Ca2+ transporters and pumps of the cell membrane,
      endoplasmic reticulum, and mitochondria were selectively blocked with
      pharmacological agents. Bath solutions containing 0 Na Ringers, chlorpromazine,
      Na3VO4, or thapsigargin did not significantly change the CAN current decay
      constants from those measured in Ringers. External 2,4-dinitrophenol or internal
      ruthenium red, however, significantly lengthened the CAN current decay constant.
      It is concluded that mitochondria are the most important sink for sub-membrane
      Ca2+ activity in the range necessary to effectively activate CAN currents.

PMID- 7520825
TI  - [Preserving intestinal function after severe burn injury].
AB  - To study the changes of the bowel-barrier function and its preservation, we
      developed a new animal model. A specially bred miniswine (Guizhou species) was
      used with multiple catheterizations for sampling different blood from portal,
      inferior mesenteric as will as jugular (central) veins. The animals were
      sustained with 30% III burns of TBSA 7 days after catheterization and divided
      randomly into early feeding (EF) group, given a complete diet beginning from 2
      hours postburn (n = 6) and delayed feeding (DF) group, given the same diet
      initiating on 4 days postburn (n = 6). The results indicated that the bowel
      barrier function was weakened significantly early postburn so that the
      translocation of both endotoxin and bacteria from the gut to portal vein was
      evidently increased. However, improving the intestinal mucosa ischemia,
      preserving mucosal mass and maintaining bowel-microecological balance through
      early enteral feeding, as revealed in this study, could enhance the barrier
      function, and the translocation of bacteria and endotoxin would be thus decreased
      to some extent.

PMID- 7520827
TI  - Expression of lipoprotein lipase during differentiation of cultured L6 muscle
      cells.
AB  - The presence of lipoprotein lipase (LPL) in L6 muscle cells is equivocal.
      Analysis of a 21-day time course indicates that these cells express both LPL
      activity and mRNA. Lipase activity peaked at 4 days after plating and decreased
      to a nadir at day 21 after plating. Characterization of lipase activity at 4 and
      19 days after plating, corresponding to myoblasts and myotubes, respectively,
      indicated that most of the enzyme activity had the properties of LPL, including
      an alkaline pH optimum, a serum requirement, and inhibition by NaCl. LPL mRNA
      expression peaked at 7 days after plating and fell slightly (24%) at day 21. The
      primary LPL mRNA species in these cells is 3.7 kb in length. Lipase activity and
      LPL mRNA were highly correlated during the nine course (r = +0.82), suggesting
      transcriptional regulation of the enzyme. These data clearly demonstrate that L6
      cells express LPL during differentiation.

PMID- 7520826
TI  - Calcium-sensitive potassium current in isolated canine coronary smooth muscle
      cells.
AB  - This study characterizes K+ current in canine coronary artery and investigates
      its role in regulation of vascular smooth muscle tone during the resting and
      activated state. Isolated rings and whole-cell K+ current as well as single K+
      channels were studied. Tetraethylammonium (< 3 mM) did not increase the resting
      tension in isolated rings; however, 0.3 mM tetraethylammonium increased tension
      in vessels that were precontracted by elevated [K+]o or 5-hydroxytryptamine (5
      HT). The whole-cell K+ current showed voltage and Ca2+ dependency and sensitivity
      to tetraethylammonium (31 +/- 7, 72 +/- 2, and 83 +/- 4% depression by 1, 10, and
      30 mM tetraethylammonium, respectively). A large-conductance (100 pS) K+ channel
      was identified in cell-attached patches with open-time distribution fitted with
      two exponentials. Calcium ionophore A23187 (10 microM) increased the probability
      of opening, mean open time, and amplitude of this channel in cell-attached
      patches, suggesting Ca2+ dependency. A23187 shifted the plot of unitary current
      as a function of pipette potential to the right, suggesting A23187-induced cell
      hyperpolarization. In inside-out patches, increase in cytoplasmic-side [Ca2+]
      from 10(-7) to 10(-6) M increased both the frequency of channel opening and
      duration of the open state, without changing its conductance. Tetraethylammonium
      (1 mM) on the cytoplasmic side caused a reversible decrease in the current
      amplitude. Charybdotoxin (100 nM) decreased the probability of opening and mean
      open time and increased mean closed time, while apamin (100 nM) did not
      significantly affect channel kinetics. In summary, this study demonstrates the
      existence and important functional role of a large-conductance, Ca(2+)-sensitive
      K+ channel in regulation of membrane potential and cell excitability, as well as
      some aspects of regulation and kinetics of this channel in canine coronary
      arterial cells.

PMID- 7520828
TI  - Survey of cytotoxin production among Escherichia coli strains characterized as
      enteropathogenic (EPEC) by serotyping and presence of EPEC adherence factor (EAF)
      sequences.
AB  - A total of 108 Escherichia coli strains characterized as enteropathogenic (EPEC)
      by serotyping and the presence of EPEC adherence factor (EAF) sequences were
      examined for cytotoxin production by cell line assays and colony hybridization
      with Shiga-like toxin (SLT) probes. Cytolethal distending toxin (CLDT) production
      was found in three (2.8%) strains belonging to serotype O86:H34, while one
      O111ab:NM strain hybridized with a SLT-II probe but did not express any cytotoxic
      activity. All four strains showed localized adherence to HeLa cells and
      hybridized to an E. coli attaching-effacing gene (eae) probe. The CLDT-producing
      strains had multiple plasmids and some were present in all strains, including a
      plasmid of approximately 54 MDa that hybridized with the EAF probe.

PMID- 7520829
TI  - Management of the woman with threatened birth of an infant of extremely low
      gestational age. Fetus and Newborn Committee, Canadian Paediatric Society,
      Maternal-Fetal Medicine Committee, Society of Obstetricians and Gynaecologists of
      Canada.
AB  - OBJECTIVE: To offer guidelines for parents, physicians and other members of the
      health-care team for management of the probable birth of an infant with a
      gestational age of 26 completed weeks or less. OPTIONS: Vaginal birth or birth by
      cesarean section for fetal indications and active treatment or palliative care of
      the infant at birth. OUTCOMES: Increased risk of complications for the mother
      from cesarean section at this stage of pregnancy and the difficulty in making a
      prognosis before or at birth for an infant of this gestational age. EVIDENCE:
      Published survival rates and risks of impairment or disability for infants of
      each gestational age; current information provided by directors of follow-up
      clinics in Canadian university-based pediatric programs. VALUES: The recommended
      management of the woman and her fetus or infant is based on many underlying
      considerations, including the best interests of the mother and her infant and the
      views of fully informed parents. BENEFITS, HARMS AND COSTS: Use of these
      guidelines will enable health care providers to offer parents of infants of
      extremely low gestational age therapeutic choices before birth based on full
      information on likely outcomes, to avoid unnecessary cesarean section and to
      minimize suffering when treatment of infants is not in their best interests.
      RECOMMENDATIONS: According to current Canadian outcome data, fetuses with a
      gestational age of less than 22 completed weeks are not viable and those with an
      age of 22 weeks rarely viable. Their mothers are not, therefore, candidates for
      cesarean section, and the newborns should be provided with compassionate care,
      rather than active treatment. The outcomes for infants with a gestational age of
      23 to 24 completed weeks vary greatly. Careful consideration should be given to
      the limited benefits for the infant and potential harms of cesarean section, as
      well as to the expected results of resuscitation at birth. Cesarean section, when
      indicated, and any required neonatal treatment are recommended for infants with
      gestational ages of 25 and 26 completed weeks; most infants of this age will
      survive, and most survivors will not be severely disabled. Treatment of all
      infants with a gestational age of 22 to 26 weeks should be tailored to the infant
      and family and should involve fully informed parents. VALIDATION: Members of the
      Fetus and Newborn Committee of the Canadian Paediatric Society (CPS) were
      involved in the preparation of this article, which was reviewed and modified by
      the Ethics Committee of the CPS and the Maternal-Fetal Medicine Committee of the
      Society of Obstetricians and Gynaecologists of Canada (SOGC). A draft was
      circulated to Canadian university-based perinatal programs and members of the
      Section on Neonatal-Perinatal Medicine of the CPS. Comments from physicians and
      bioethicists were incorporated, when possible, into the final version. There are
      no similar guidelines in North America.

PMID- 7520830
TI  - Euthanasia debate could be obstacle to effective pain control, meeting told.

PMID- 7520831
TI  - Modulation of allergen-specific antibody responses by T-cell-based peptide
      vaccine(s). Principles and potential.

PMID- 7520832
TI  - Contortrostatin, a snake venom disintegrin, inhibits beta 1 integrin-mediated
      human metastatic melanoma cell adhesion and blocks experimental metastasis.
AB  - Disintegrins are Arg-Gly-Asp-containing proteins that inhibit integrin-mediated
      cell-cell and cell-matrix interactions. We have purified a disintegrin,
      contortrostatin, from Agkistrodon contortrix contortrix snake venom that is a
      potent inhibitor of human metastatic melanoma (M24 met) cell adhesion to
      extracellular matrix proteins. Contortrostatin inhibits M24 met cell adhesion to
      type I collagen, vitronectin, and fibronectin with 50% inhibitory concentration
      values of 20, 75, and 220 nM, respectively. Contortrostatin does not
      significantly inhibit adhesion of M24 met cells to laminin. 125I-labeled
      contortrostatin binds to M24 met cells in a saturable and displaceable manner.
      Scatchard analysis indicates that there are two binding sites for 125I-labeled
      contortrostatin on the surface of these cells. High affinity binding has a Kd of
      3 nM with 165,000 sites/cells low affinity binding has a Kd of 60 nM with 500,000
      sites/cell. Immobilized contortrostatin can support adhesion of M24 met cells;
      this binding is blocked by a monoclonal antibody to the beta 1 integrin subunit
      and by an antibody to the fibronectin receptor alpha 5 beta 1. The anti
      vitronectin receptor (alpha v beta 5) monoclonal antibody which blocks adhesion
      of M24 met cells to immobilized vitronectin does not block binding of M24 met
      cells to immobilized contortrostatin. In an in vivo experimental metastasis model
      system, contortrostatin at 20 micrograms and 100 micrograms inhibits lung
      colonization of M24 met cells (5 x 10(5)), injected in the tail vein of scid
      mice, by 51 and 73%, respectively. We conclude that contortrostatin is a potent
      inhibitor of beta 1 integrin-mediated M24 met cell adhesion in vitro and that it
      also inhibits lung colonization in vivo.

PMID- 7520833
TI  - Improved synthesis and the crystal structure of methyl 4,6-dideoxy-4-(3-deoxy-L
      glycero-tetronamido)-alpha-D-mannopyrano side, the methyl alpha-glycoside of the
      intracatenary repeating unit of the O-polysaccharide of Vibrio cholerae O:1.
AB  - The crude product of deamination of the commercially available L-homoserine was
      acetylated and the 2-O-acetyl-3-deoxy-L-glycero-tetronolactone (18) formed was
      used to N-acylate methyl perosaminide (methyl 4-amino-4,6-dideoxy-alpha-D
      mannopyranoside, 12) and its 2,3-O-isopropylidene derivative. The major product
      isolated from the reaction was the crystalline methyl 4-(4-O-acetyl-3-deoxy-L
      glycero-tetronamido)-4,6-dideoxy-alpha-D-+ ++mannopyranoside (1, 70-75%)
      resulting from acetyl group migration in the initially formed 2'-O-acetyl
      derivative. O-Deacetylation of 1 gave the title amide 2. Compound 2, obtained
      crystalline for the first time, was fully characterized, and its crystal
      structure was determined. Deoxytetronamido derivatives diastereomeric with 1 and
      2, respectively, were obtained by the acylation of 12 with 2-O-acetyl-3-deoxy-D
      glycero-tetronolactone (prepared from D-homoserine), and subsequent
      deacetylation. Structures of several byproducts of the reaction of 12 with 18
      have been deduced from their spectral characteristics. Since these byproducts
      were various O-acetyl derivatives of 2, the title compound could be obtained in
      approximately 90% yield by deacetylating (Zemplen) the crude mixture of N
      acylation products, followed by chromatography.

PMID- 7520834
TI  - The structure of the O-antigenic chain of the lipopolysaccharide of Rhizobium
      trifolii 4s.
AB  - The structure of the O-antigen chain of the lipopolysaccharide (LPS) of Rhizobium
      trifolii 4s has been determined by a combination of chemical and spectroscopic
      methods. The glycosyl components were found to be L-rhamnose, N-acetyl-D
      glucosamine, and N-acetyl-D-mannosamine in 3:1:1 molar proportion, as determined
      by gas chromatography and gas chromatography-mass spectrometry of alditol acetate
      and persilylated (R)-2-hydroxybutyl glycoside derivatives. The linkage positions
      and configurations of the glycosyl residues were obtained by 1D and 2D NMR
      spectroscopy. The polymer has a pentasaccharide repeating-unit containing
      rhammose and N-acetylglucosamine in the main chain and N-acetylmannosamine as the
      sole-side chain component. This latter residue is linked to a main-chain rhamnose
      residue. This result was suggested by NMR spectroscopy and confirmed by periodate
      oxidation. The sequence was deduced by 1D and 2D NMR NOE experiments and by
      partial hydrolysis studies. The repeating unit of the polysaccharide is shown.
      This constitutes the first complete structure of an O-antigenic chain of the
      lipopolysaccharide of any strain of Rhizobium trifolii.

PMID- 7520835
TI  - The use of lectins in monitoring degradation of oligosaccharide chains in mucin
      by oral streptococci.
AB  - The ability of utilize mucin oligosaccharides as sources of carbohydrate and
      energy is believed to be an important mechanism in the ecology of oral
      streptococci. In this study we have used digoxigenin-labelled lectins of various
      specificities to monitor changes in the nonreducing end groups of oligosaccharide
      chains following their degradation by Streptococcus oralis Ny 586 and
      Streptococcus sanguis Ny 584. The reaction of degraded mucin with peanut lectin,
      that recognizes the core disaccharide Gal (1,3)GalNAc in O-glycans, revealed a
      more extensive degradation of oligosaccharide by S. oralis than by S. sanguis.
      This corresponds to better growth of S. oralis on the mucin. Analyses with Datura
      stramonium lectin showed that terminal Gal (1,4)GlcNAc, or GlcNAc (1,4)GlcNAc
      moieties, in the oligosaccharides are attacked by both strains. Reaction patterns
      with alpha-L-fucose-specific lectins indicated that terminal fucose was released
      by S. oralis but not by S. sanguis. This was in accordance with sugar analyses
      which showed that approximately 40% of the fucose units were released. The
      results extend previously observed losses of sugars from oligosaccharide chains
      during growth of these organisms on mucin.

PMID- 7520836
TI  - Regions of the CD8 molecule involved in the regulation of CD2-mediated
      activation.
AB  - The CD8 molecule regulates T cell activation mediated via the CD3 T cell receptor
      and the adhesion molecule CD2. CD8 mAbs have been found to inhibit early (Ca2+
      rise) as well as late events (cytotoxicity, proliferation, and lymphokine
      secretion) mediated via the CD2 pathway. A panel of eight anti-human CD8 mAbs was
      tested for inhibition of CD2-mediated Ca2+ rise in a cytotoxic T cell clone. The
      inhibition ranged from 5 to 53% independently of mAb isotype and affinity
      measured by half saturation binding. We then characterized these mAbs for their
      reactivity toward three mutants of the human CD8 alpha carrying amino acid
      sequence changes in the surface-exposed loops homologous to the immunoglobulin
      CDR1, 2, and 3. The mutations included replacement of the human CD8 alpha CDR1-
      and CDR2-like loops by the homologous mouse sequences and the insertion of a
      glycine in the middle of the CDR3-like loop. Thus, five mAbs were found to be
      affected by the mutation in the CDR2-like loop but not by alterations in the
      other CDR-like loops. Conversely, the other two mAbs (8E1.7 and B9.8) were
      affected only by mutations in the CDR1- and CDR3-like loops, respectively. Cross
      inhibition experiments were essentially in agreement with these results.
      Interestingly, all the mAbs directed against the CDR2-like loop were potent
      inhibitors of CD2-mediated Ca2+ rise, with one exception probably due to poor
      affinity. Thus, in addition to being a site of interaction with major
      histocompatibility complex Class I as recent data have indicated, this region of
      the CD8 alpha subunit may play a role in regulating T cell activation.

PMID- 7520837
TI  - Induction of interferon-gamma, interleukin-4, and transforming growth factor-beta
      in rats orally tolerized against experimental autoimmune myasthenia gravis.
AB  - Oral administration of nicotinic acetylcholine receptor (AChR) to Lewis rats
      prior to myasthenogenic immunization with Torpedo AChR+complete Freund's adjuvant
      (CFA) results in the prevention of experimental autoimmune myasthenia gravis
      (EAMG) and the suppression of AChR-specific B cell responses and counteracts the
      development of AChR-reactive interferon-gamma (IFN-gamma) secreting T cells. To
      study the involvement of the T helper type 1 (Th1) cell-related lymphokine IFN
      gamma, the Th2 cell-related interleukin-4 (IL-4), and transforming growth factor
      beta (TGF-beta) that suppresses the synthesis of IFN-gamma and IL-4, we used in
      situ hybridization with complementary DNA oligonucleotide probes to enumerate
      mononuclear cells (MNC) expressing mRNA for the cytokines IFN-gamma, IL-4, and
      TGF-beta. Upon in vivo recognition of AChR, popliteal, inguinal, and mesenteric
      lymph nodes, spleen and thymus of rats with EAMG contained higher levels of IFN
      gamma, IL-4, and TGF-beta mRNA-expressing cells compared to CFA-injected control
      rats, implicating the involvement in EAMG of AChR-reactive Th1 and Th2 cells in
      parallel. TGF-beta was also upregulated in EAMG. Oral tolerance to EAMG was
      characterized by suppression of the levels of MNC expressing IFN-gamma and IL-4,
      but augmentation of cells expressing TGF-beta. The results suggest that IFN
      gamma, IL-4, and TGF-beta are involved in the development of EAMG, and that TGF
      beta is important in the induction of oral tolerance to EAMG.

PMID- 7520838
TI  - Oral tolerance to myelin basic protein induces regulatory TGF-beta-secreting T
      cells in Peyer's patches of SJL mice.
AB  - Oral administration of myelin basic protein (MBP) is an effective means of
      suppressing experimental autoimmune encephalomyelitis (EAE). In the Lewis rat
      model, we have previously shown that this effect is mediated by active
      suppression as T lymphocytes from animals orally tolerized to MBP suppress in
      vitro immune responses and in vivo adoptively transfer disease protection to
      naive recipients. This effect is mediated by the cytokine TGF-beta which is
      secreted by T cells from orally tolerized animals after being triggered by the
      oral tolerogen. In the present study we investigated Peyer's patches in SJL mice
      following orally administered MBP. Peyer's patches are one of the major lymphoid
      structures of gut-associated lymphoid tissue, and a site thought to play an
      important role in the induction of oral tolerance. Twenty-four hours after one
      feeding of 1 mg of MBP, there were no proliferative responses to MBP in Peyer's
      patches. However, when Peyer's patches from MBP-fed animals were stimulated with
      IL-2 in the presence of MBP, reduced proliferation to IL-2 was observed, and this
      inhibition was reversed with anti-TGF-beta antibody. Suppression of IL-2-induced
      proliferation by MBP was not observed in unfed animals or if Peyer's patches from
      MBP-fed animals were stimulated with a control antigen (ovalbumin). Stimulation
      of Peyer's patches T cells from MBP-fed animals with MBP resulted in secretion of
      TGF-beta in a dose-related fashion with less TGF-beta secretion at higher doses.
      Furthermore, cells from Peyer's patches of animals fed MBP adoptively transferred
      protection to actively induced EAE. Thus, MBP-specific TGF-beta-secreting
      regulatory cells recovered from Peyer's patches after a single oral
      administration of MBP are not evident as measured by proliferation, but are
      capable of suppressing in vitro and in vivo cell-mediated immune responses.
      Peyer's patches appear to be an important site for the induction of cells which
      mediate the active suppression component of oral tolerance.

PMID- 7520839
TI  - Glutamylated tubulin probed in ciliates with the monoclonal antibody GT335.
AB  - Microtubular networks are extensively developed in many ciliate species. In
      several of them, we investigate the occurrence of the post-translational
      glutamylation of tubulin [Edde et al., 1990: Science 247:82-85; Edde et al.,
      1991: J. Cell. Biochem. 46:134-142] using as a probe for such modified tubulin,
      the monoclonal antibody GT335 [Wolff et al., 1992: Eur. J. Cell Biol. 59:425
      432]. Results obtained in Paramecium strongly suggest that both axonemal and
      cytoplasmic tubulin are glutamylated. As in the vertebrate brain tubulin so far
      tested, the GT335 epitope is located at the carboxy-terminal fragment of
      cytoplasmic tubulin removed by subtilisin treatment. Immunoblotting and
      immunofluorescence experiments reveal that, unlike tubulin acetylation,
      glutamylation is not restricted to cold-resistant microtubules. In addition,
      immunofluorescence studies performed on dividing cells show that glutamylation
      takes place soon after the polymerization of microtubules. Finally, glutamylated
      tubulin is also detected in the ciliate species Euplotes, Tetrahymena, and
      Paraurostyla. Together with results obtained on flagellate species, this suggests
      that tubulin glutamylation came out early in the course of eukaryotic evolution
      and has been widely exploited in various cellular strategies.

PMID- 7520840
TI  - Angiogenic activity of a fusion protein of the cell-binding domain of fibronectin
      and basic fibroblast growth factor.
AB  - We constructed a fusion protein of the cell-binding domain of human fibronectin
      and human basic fibroblast growth factor, and prepared a polypeptide with both
      cell-adhesive activity and growth factor activity. A human gene fragment coding
      for basic fibroblast growth factor was amplified by the polymerase chain
      reaction, and introduced into the expression vector pTF7520, which encodes the
      cell-binding domain of human fibronectin. The resulting plasmid encoded a fusion
      protein in which basic fibroblast growth factor was added covalently to the C
      terminal end of the fibronectin fragment. The fusion protein was expressed in
      Escherichia coli JM109 cells and purified from the extract by heparin affinity
      chromatography. The purified fusion protein had cell-adhesive activity toward
      BALB/c 3T3 cells, and stimulated their DNA synthesis in serum-depleted cultures.
      The fusion protein gave maximum mitogenic activity at the concentration of 10 nM.
      The fusion protein adsorbed to culture dishes, or added to collagen gels,
      stimulated the growth of human umbilical-vein endothelial cells. The fusion
      protein stimulated the angiogenesis in chorioallantoic membranes of developing
      chick embryos.

PMID- 7520841
TI  - Differential expression of colony-stimulating factor (CSF) in murine macrophage
      clones: interferon-gamma-mediated inhibition of CSF production.
AB  - Bioassay and northern blot analyses revealed that, among several functional
      murine macrophage (M phi) clones, lipopolysaccharide (LPS) stimulation generated
      in distinct induction levels of granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony
      stimulating factor (M-CSF). When compared with these induction profiles, the M
      phi clones could be classified into two types; G type (G-CSF GM-CSF-M-CSF+) and
      GM type (G-CSF +/- GM-CSF M-CSF+) of M phi clones. Unlike G-CSF and GM-CSF that
      were inducible factors, M-CSF mRNA was constitutively expressed without
      stimulation and was differentially controlled between the G and GM types; LPS
      induction decreased M-CSF mRNA in the former, but increased it in the latter.
      Further northern blot analysis revealed that interferon-gamma (IFN-gamma)
      suppressed constitutive expression of M-CSF mRNA, and that costimulation with
      both LPS and IFN-gamma reduced expression of G-CSF and M-CSF mRNA in the G type
      of M phi clone, but induced higher expression of GM-CSF and M-CSF mRNAs in the GM
      type of M phi clone compared with LPS alone. However, in either case, IFN-gamma
      completely inhibited LPS-induced production of active CSF of the M phi clones,
      which was observed even in IFN-gamma pretreatment, and also abrogated
      autoactivation of GM-CSF. Our present results suggested that murine M phi clones
      had differentially regulated expression of CSFs and that IFN-gamma had a
      regulatory function of inhibiting CSF production of murine M phi s.

PMID- 7520842
TI  - Fungal metabolites. XVII. Synthesis and NMR study of ion channel-forming
      peptides, trichosporin B-VIa and its derivative.
AB  - A membrane-modifying peptide antibiotic, trichosporin B-VIa, having catecholamine
      secretion-inducing activity on bovine adrenal chromaffin cells has been
      synthesized. Aib14-Trichosporin B-VIa, in which Pro14 was replaced by Aib, has
      also been synthesized to modify the secondary structure of trichosporin B-VIa.
      Sequence-specific 1H-NMR assignments of both peptides in methanol were achieved
      by using two-dimensional NMR techniques.

PMID- 7520843
TI  - Effect of pharmacologic doses of zinc on the therapeutic index of brain tumor
      chemotherapy with carmustine.
AB  - To evaluate the potential differential effect of pretreatment with pharmacologic
      doses of the trace element zinc on the chemosensitivity of glioma cells and bone
      marrow cells for carmustine (BCNU), we performed in vitro and in vivo studies of
      zinc toxicity as well as of the combined treatment with zinc and the anticancer
      drug. We studied the in vitro effects on established human and rat glioma cell
      lines using a microcolorimetric growth assay and on murine bone marrow using a
      clonogenic assay for committed progenitor cells of the granulocyte-monocyte
      lineage. Zinc exposures of up to 100 microM for 120 h did not influence the
      growth of six of seven human glioma cell lines. Only U87MG demonstrated
      statistically significant toxicity during high zinc exposure (100 microM over 120
      h). Dose-response growth curves generated for BCNU did not show protection
      against the anticancer agents by a 48-h pretreatment with different zinc
      concentrations. The clonogenic capacity of bone marrow cells was slightly reduced
      by in vitro culture for 24 and 48 h. Although this effect appeared to be more
      prominent in the presence of zinc supplementation, overall a statistically
      significant inhibition was seen only after exposure to a concentration of 100
      microM zinc over 48 h. As compared with chemotherapy alone, in vitro pretreatment
      with 50 microM zinc over 48 h followed by chemotherapy resulted in an increased
      number of colony-forming unit-granulocyte monocyte (CFU-GM): CFU-GM increased by
      a factor of 2 for BCNU (60 microM x 2 h). This statistically significant in vitro
      chemoprotection would translate into a dose-protection factor of 1.5, i.e., for
      the same level of myelosuppression, zinc pretreatment would allow administration
      of a 50% increased dose of BCNU. The in vivo studies were performed in an s.c.
      xenograft model of the human glioma cell line U87MG in athymic mice. The maximal
      tolerable pretreatment with zinc was determined to be a 10-day course of daily
      i.p. injections of 10 mg/kg ZnCl2. The subsequent i.p. administration of the dose
      lethal to 10% of the mice (LD10) and of a 1.5 x LD10 dose of BCNU resulted in
      less bone marrow toxicity in pretreated animals than in non-zinc-pretreated mice
      as determined in a CFU-GM assay. Glioma colony-forming efficiency (CFE) assays,
      on the other hand, did not show any zinc-related difference in the BCNU
      sensitivity of U87MG.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7520844
TI  - Camptothecin analogues: studies from the Johns Hopkins Oncology Center.
AB  - The camptothecin analogues topotecan and irinotecan (CPT-11) are active
      anticancer drugs. This article reviews the accumulated results of clinical and
      laboratory studies performed with these agents at The Johns Hopkins Oncology
      Center. In a phase I clinical and pharmacology trial of topotecan given as a 30
      min infusion daily for 5 days every 3 weeks, profound neutropenia precluded dose
      escalation above 1.5-2.0 mg/m2 per day, the maximum tolerated dose (MTD). The
      daily x5 schedule has been developed further with dose escalation using
      granulocyte-colony-stimulating factor support in patients who have kidney or
      liver dysfunction and given in combination with cisplatin. In addition, a phase I
      trial of topotecan given as a 5-day continuous intravenous infusion to patients
      with refractory leukemia has had promising antileukemic responses. A separate
      series of in vitro studies indicates that a modest degree of resistance to the
      cytotoxicity of topotecan can be mediated by P-glycoprotein. A phase I and
      pharmacology study of irinotecan given as a 90-min infusion every 3 weeks has
      defined an MTD of 240 mg/m2, with dose escalation being limited by several
      toxicities. These included an acute treatment-related syndrome of flushing,
      warmth, nausea, vomiting, and diarrhea; a subacute combination of nausea,
      diarrhea, anorexia, and weight loss; and/or neutropenia. Antitumor activity has
      been observed with topotecan and irinotecan in patients with a variety of solid
      tumors and refractory leukemia in our studies, which supports the widespread
      enthusiasm for this group of compounds.

PMID- 7520845
TI  - A new rapid immunoinhibition pancreatic amylase assay: diagnostic value for
      pancreatitis.
AB  - A new rapid immunoinhibition pancreatic amylase assay was compared to total
      amylase and lipase in an unbiased sample of 1005 emergency department patients
      with suspicion of pancreatitis, of which 55 had a final diagnosis of
      pancreatitis. Imprecision of the assays for both amylases (less than 2.5%) were
      better than for lipase (less than 6.1%). Correlation (R2) of pancreatic amylase
      with total amylase was 0.991 but only 0.789 with lipase. Using Receiver Operator
      Characteristics analysis, the best diagnostic cutoff point for all three enzymes
      was near the upper limit of the reference interval. With pancreatic amylase,
      sensitivity, specificity, and predictive values for positive and negative results
      are, respectively, 85.5, 92.5, 39.8, and 99.1%; we found similar values for
      lipase but poorer values (78.2, 92.0, 36.1, and 98.7%) for total amylase. Tests
      combination did not improve the diagnostic performance significantly. In the
      diagnosis of pancreatitis, pancreatic amylase (p = 0.037) and lipase (p = 0.049)
      had better diagnostic performance than total amylase. The correct diagnosis of
      pancreatitis could be achieved in 47 instead of 43 patients with either
      pancreatic amylase or lipase as opposed to total amylase among 1005 patients in
      this study. We conclude that pancreatic amylase and lipase are incrementally
      better diagnostic tools than total amylase for the diagnosis of pancreatitis.

PMID- 7520846
TI  - Immunoreactive prostate-specific antigen levels in female and male breast tumors
      and its association with steroid hormone receptors and patient age.
AB  - Prostate-specific antigen (PSA) is believed to be a highly specific marker for
      normal or cancerous prostatic tissue. We recently found that immunoreactive PSA
      (IR-PSA) is present in 30% of breast tumor cytosols (from 525 breast cancer
      patients). In this paper we analyzed a new series of 750 breast tumor cytosols,
      obtained from 744 women and six men, for IR-PSA. The positivity rates in the old
      and new series were very similar (approximately 30%). Combining the two series of
      breast cancer patients, we examined the associations between IR-PSA and estrogen
      (ER) or progesterone (PR) receptors, or patient age. We found that IR-PSA
      positivity rate declines with age. PSA-positive tumors were highly associated
      with either ER-positive or PR-positive tumors alone. However, analysis in a
      subset of tumors that combine the two receptors, ER(-)/PR(-), ER(+)/PR(-), ER(
      )/PR(+), and ER(+)/PR(+), revealed that IR-PSA was only associated with PR, and
      no relationship was found between IR-PSA and ER. We speculate that the presence
      of IR-PSA in breast cancer may be associated with the PR action and that the
      association between PSA and ER is indirect due to the known association between
      ER and PR. As five of the six male breast tumors were found negative for IR-PSA,
      it is suggested that androgen may not be involved in the presence of IR-PSA in
      breast tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520847
TI  - Time-resolved immunofluorometric assay of trypsin-2 complexed with alpha 1
      antitrypsin in serum.
AB  - We developed a sensitive time-resolved immunofluorometric assay (IFMA) for
      trypsin-2 complexed with alpha 1-antitrypsin (AAT). We used a trypsin-2-specific
      monoclonal antibody on the solid phase and a europium-labeled polyclonal antibody
      to AAT as tracer. The detection limit is 0.05 microgram/L and the range of
      linearity extends to 100 micrograms/L. We compared the clinical utility of the
      trypsin-2-AAT assay with that of free trypsinogen-2 and amylase in serum by
      studying 120 healthy subjects, 29 patients with acute pancreatitis, 11 with
      extrahepatic biliary obstruction, and 34 with acute abdominal disorders of
      extrapancreatic origin. In patients with acute pancreatitis the median
      concentration of trypsin-2-AAT in serum was 59-fold that in healthy controls, 42
      fold that in patients with biliary obstruction, and 33-fold that in patients with
      acute abdominal disorders of extrapancreatic origin. These differences are
      greater than those for trypsinogen-2 (19-, 20-, and 28-fold, respectively) and
      amylase (5.4-, 6.5-, and 5.4-fold, respectively). Compared with the assays of
      free trypsinogen-2 and amylase, our assay of trypsin-2-AAT improved the clinical
      specificity for acute pancreatitis by eliminating false-positive results in our
      control groups. Increased concentrations of trypsin-2-AAT and trypsinogen-2 were
      also observed in patients with chronic renal failure undergoing dialysis.

PMID- 7520848
TI  - The genetic defect of PNH.

PMID- 7520849
TI  - Tutorial. Molecular biology for the clinician. Part I. General principles.
AB  - A fundamental understanding of all biological processes requires an understanding
      of the molecular basis of cellular function. The discipline of molecular biology
      focuses on the genetic information in cells: how is the inherited information
      encoded within DNA and how is this information regulated and expressed so that
      the cells of a multicellular organism develop from a single cell to highly
      specialized cells in a complex and integrated organism? For the practicing
      clinician, an understanding of the molecular mechanisms by which a differentiated
      cell develops and maintains its specialized functions is critical to a more in
      depth understanding of human diseases. This is the 1st of a 3 part series on
      molecular biology for the clinician. This article introduces general principles
      of nucleic acid and gene structure. The 2nd article will examine commonly used
      research and diagnostic techniques based on the principles of molecular biology.
      The 3rd part will examine the frontiers of gene therapy, a novel approach to the
      treatment human diseases at the molecular level.

PMID- 7520850
TI  - Differential staining of Dugesia tigrina sister chromatids.
AB  - Planaria were cultured in a solution of bromodeoxyuridine (BrdU) for 24 h in an
      attempt to produce sister chromatid differential staining (SCD) and sister
      chromatid exchange (SCE). SCD was produced when planaria were cultured in
      planarian saline solution (PSS) containing 5 x 10(-5) M BrdU. Colchicine (0.02%)
      was added to the BrdU/PSS culture medium 8 to 10 h before sacrifice. Animals were
      then vigorously dissociated into cells, centrifuged, and fixed in Carnoy's
      solution. Slides were prepared using the air-drying method, allowed to age for at
      least 1 day, stained with the fluorochrome Hoechst 33258, exposed to high
      intensity incandescent light, stained with Giemsa solution, and mounted. This
      method is the first reported SCD/SCE investigation in the Platyhelminthes and
      consistently yielded second division metaphases exhibiting SCD and third division
      metaphases exhibiting non-reciprocal SCE's composed of unifilarly BrdU-labelled
      DNA.

PMID- 7520851
TI  - [The clinical significance of platelet activation during exercise-induced
      myocardial ischemia].
AB  - The levels of alpha-granule membrane protein (GMP-140) on the surface of platelet
      and serum TXB2 were determined in 55 patients with coronary heart disease (CHD)
      and 20 healthy individuals before and after exercise test. Among the 55 CHD
      patients, 36 had positive and 19 had negative results. The number of GMP-140
      molecules on the platelet surface and serum TXB2 level were significantly
      increased in the patients with positive exercise test, P < 0.05. The increase was
      transient and GMP-140 returned to the preexercise level 15 minutes after the
      exercise test. In contrast, GMP-140 and TXB2 levels were not elevated in CHD
      patients with negative exercise test and also in normal subjects after exercise.
      The result indicates that platelet activation may be related to the exercise
      induced myocardial ischemia in CHD patients.

PMID- 7520852
TI  - Reversible and irreversible interactions of a cisplatin analog bearing a 1,2
      diphenylethylenediamine ligand with plasma and plasma proteins in vitro.
AB  - The cisplatin analog [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)
      ethylenediamine]dichloroplatinum(II) [PtCl2(1)], by virtue of its estrogenic 1,2
      diphenylethylenediamine ligand 1, was intended to function as a cytotoxic
      estrogen. This article reports on the reversible and irreversible interactions of
      this compound with plasma and plasma proteins in vitro. At 37 degrees C
      [PtCl2(1)] is > 99% reversibly bound to proteins in plasma. At 0 degree C
      [PtCl2(1)] reversibly binds to albumin at specific binding sites not shared by 1.
      By use of HPLC the in vitro half-life of total [PtCl2(1)] in plasma was found to
      be 35 min at 37 degrees C, which is approximately 1/3 the half-life reported for
      cisplatin under similar conditions. To understand this decreased stability,
      irreversible reactions of [PtCl2(1)] with albumin and plasma globulins were
      investigated. The reaction rate of [PtCl2(1)] with albumin is independent of the
      protein concentration and is comparable to the rate of the first Pt-Cl hydrolysis
      reaction. Thus, [PtCl2(1)], like cisplatin, reacts irreversibly with albumin
      through a solvent-assisted SN2 substitution pathway. Because the hydrolysis rate
      for [PtCl2(1)] is 40% slower than for cisplatin, irreversible reactions of
      [PtCl2(1)] with albumin cannot account for the decreased stability of the
      compound in plasma. alpha-Globulins undergo substitution reactions with
      [PtCl2(1)] by both solvent-assisted and direct SN2 pathways. The half-life of
      [PtCl2(1)] in the presence of alpha-globulins at concentrations normally present
      in plasma (6-16 g/liter) is from 41 to 22 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520853
TI  - New pharmacological approaches to insulin and lipid metabolism.

PMID- 7520854
TI  - Do non-potassium-sparing diuretics increase the risk of sudden cardiac death in
      hypertensive patients? Recent evidence.
AB  - Whether non-potassium-sparing diuretics (NPSD) increase the risk of sudden
      cardiac death in hypertensive patients has been vigorously debated. Diuretic
      induced potassium or magnesium depletion leading to cardiac arrhythmias has been
      suggested as the underlying mechanism. A clear dose-response relationship between
      NPSD and the reduction in serum K+ exists. Data regarding serum Mg++ and
      intracellular K+ and Mg++ are too limited to allow conclusions. NPSD seem to
      increase the risk of ventricular arrhythmias among hypertensive patients with
      clinical evidence of heart disease, but the number of studies is small. The
      findings among patients without evidence of heart disease are less conclusive.
      The interpretation of the studies on electrolyte changes and arrhythmias
      following diuretic therapy is obscured by the fact that only a minority of
      studies included a randomly allocated placebo-treated control group. The large
      hypertension trials provide the strongest evidence that NPSD for hypertension may
      induce sudden death. Although blood pressure lowering may be expected to reduce
      the incidence of sudden cardiac death, the incidence in the NPSD group is similar
      to or even higher than that in the control group in 9 of 10 trials. We conclude
      that the beneficial effect of NPSD therapy for hypertension is partly offset by
      an excess risk of sudden death. Thus, alternative drugs, notably potassium
      sparing diuretics or beta-blockers, could be preferred as antihypertensive drugs
      of first choice, although the efficacy of beta-blockers in older patients has
      recently been challenged.

PMID- 7520855
TI  - Treatment of oral Candida mucositis infections.
AB  - Infections due to Candida spp. are increasing in incidence as the number of
      immune compromised patients increases. The common presentation of Candida
      mucositis and oral infections includes atrophic candidiasis, angular cheilitis,
      leukoplakia and oesophagitis. An increasing spectrum of antifungal agents,
      including imidazoles, are available for treatment and suppression of this common
      infection. In chronically immune-compromised patients such as those with severe
      HIV related immune deficiency, eradication of the infection may not be possible.
      This requires a stepwise approach to management and may require the use of
      potent, toxic agents such as amphotericin B to suppress the symptoms and signs of
      infection sufficiently to provide the patient with symptomatic relief. Resistant
      organisms are also becoming a greater problem in this patient population.

PMID- 7520857
TI  - Management of HIV-related bodyweight loss.
AB  - Involuntary bodyweight loss is a frequent manifestation of HIV infection and
      ultimately affects the majority of patients. Because it portends a poor prognosis
      and adversely affects quality of life, nutritional intervention has an important
      role in the care of all HIV-infected persons. The mechanism of HIV-related
      bodyweight loss is multifactorial and includes complex interactions between
      decreased caloric intake, malabsorption and metabolic and/or hormonal
      abnormalities. Treatment of reversible and identifiable causes of bodyweight loss
      such as opportunistic infections and adverse effects of therapy are essential for
      the maintenance of bodyweight. For patients with anorexia of unclear aetiology,
      there are effective appetite stimulants available. Enteral and parenteral
      alimentation are under evaluation for their role in maintenance and/or repletion
      of bodyweight for patients with HIV infection.

PMID- 7520856
TI  - Depot antipsychotic drugs. Place in therapy.
AB  - The pharmacokinetics of depot antipsychotic medications are such that an
      intramuscular injection given at intervals of from 1 to 4 weeks will produce
      adequate plasma concentrations that are sufficient to prevent relapse over the
      dosage interval. Such medication is useful in patients who do not reliably take
      their oral medication. The pharmacokinetics and clinical actions of various depot
      formulations of antipsychotic drugs have been extensively studied. Unfortunately,
      patients who do not reliably take their oral medications are unlikely to
      volunteer for controlled studies. This is because the same factors that influence
      a patient to not cooperate with the physician in taking the medication as
      prescribed will also interfere with their willingness to volunteer for research
      protocols. Thus, evidence from blinded controlled trials may not necessarily
      reflect the actual patient population at risk. We feel that particularly
      important evidence of efficacy of depot vs oral medication comes from mirror
      image studies. In these trials, the number of hospitalisations after initiation
      of depot medication is compared with that observed when the patient was solely
      taking oral medication. Studies of this type show that depot medication
      substantially reduces the rate of relapse. There is considerable evidence about
      how long depot medications should be used. For many patients, depot medication to
      prevent relapse in schizophrenia should be used for the life of the patient. As
      the conventional antipsychotic agents are replaced by a new generation of agents,
      the need for depot formulations will continue, and the knowledge gained about the
      current formulations should transfer to future generations of drugs.

PMID- 7520858
TI  - Ceftibuten. A review of its antibacterial activity, pharmacokinetic properties
      and clinical efficacy.
AB  - Ceftibuten is an orally active third generation cephalosporin which has a broad
      spectrum of in vitro antibacterial activity, encompassing the majority of Gram
      negative pathogens and streptococci, and which shows greater stability than
      several other cephalosporins against bacteria producing extended-spectrum beta
      lactamases. In clinical studies, ceftibuten (generally 400 mg/day in adults or 9
      mg/kg/day in children, administered once daily) was effective in the treatment of
      acute uncomplicated or complicated urinary tract infections, demonstrating an
      efficacy similar to that of cefaclor (1500 mg/day), and similar or superior to
      that of cotrimoxazole (trimethoprim/sulfamethoxazole; 8/40 mg/kg/day) in
      children. The majority of patients with acute or chronic lower respiratory tract
      infections responded to treatment with ceftibuten, and response rates were
      similar to those achieved with cefaclor (750 or 1500 mg/day). Ceftibuten 9
      mg/kg/day was at least as effective as cefaclor and as effective as
      amoxicillin/clavulanic acid (both 40 mg/kg/day) in children with acute otitis
      media, and was superior to phenoxymethylpenicillin (penicillin V; 25 mg/kg/day)
      in children and adolescents with streptococcal pharyngitis or scarlet fever
      caused by Group A beta-haemolytic streptococci. Ceftibuten was well tolerated in
      most patients, with adverse events (mostly mild to moderate gastrointestinal
      disturbances) generally occurring in 5 to 10% of patients. Thus, ceftibuten, with
      a once- or twice-daily oral dosage regimen, good tolerability profile and
      activity against a wide range of bacterial organisms, offers a promising
      alternative to other agents (including cefaclor, cotrimoxazole,
      amoxicillin/clavulanic acid, bacampicillin and phenoxymethylpenicillin) for the
      treatment of patients with urogenital and respiratory tract infections. Its place
      in therapy will be more clearly defined following further large comparative
      trials, in which it is likely to prove most useful in patients with infections
      caused by beta-lactamase-producing pathogens.

PMID- 7520859
TI  - Anagrelide. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic potential in the treatment of thrombocythaemia.
AB  - Anagrelide, an orally active quinazolin, induces thrombocytopenia in humans and
      has therefore been evaluated for use in conditions associated with
      thrombocythaemia. In patients with essential or myeloproliferative
      thrombocythaemia, anagrelide (usually 1 to 4 mg/day) produced sustained
      reductions in platelet counts for 1 to more than 28 months and also reduced the
      incidence of disease-related symptoms. 60 to 93% of patients responded to
      anagrelide therapy with clinically significant reductions in platelet count.
      Anagrelide has a tolerability profile different from that of most other agents
      used in the treatment of thrombocythaemia; most adverse effects are related to
      its vasodilatory or positive inotropic properties. Anagrelide has a high
      specificity towards megakaryocytes (and thus decreases platelet levels), although
      haematocrit is also reduced in some patients. If longer term trials confirm the
      lack of leukaemogenic and mutagenic potential with this drug, anagrelide may
      become the agent of choice for the treatment of thrombocythaemia, especially in
      younger patients in whom the risk of leukaemogenic transformation with some
      alternative drugs is of particular concern.

PMID- 7520861
TI  - Expression and regulation of Ly-6 differentiation antigens by murine osteoblasts.
AB  - Osteoblasts arise from mesenchymal stem cells and differentiate to become osteoid
      secreting cells. However, little is known about these cells during their stages
      of differentiation. One reason for this lack of information is that there is no
      reliable method to identify osteoblasts as they mature. One method that has been
      used successfully with other cell types is the identification of plasma membrane
      expressed differentiation antigens. The Ly-6 multigene family encodes
      differentiation antigens originally detected on lymphoid cells. Primary murine
      osteoblasts and the osteoblast-like MC3T3 cell line were examined for expression
      of Ly-6 antigens by flow cytometry. Primary osteoblasts and MC3T3 cells
      constitutively expressed both Ly-6A and Ly-6C antigens, although Ly-6C was much
      less abundant. Antigen expression was markedly increased by pretreating the cells
      with interferon-alpha/beta or -gamma. Northern blot analysis revealed
      constitutively expression of Ly-6 messenger RNA that was up-regulated by
      interferon treatment. Pretreatment of the cells with transforming growth factor
      beta 1 or 1,25-dihydroxyvitamin D3 diminished constitutive Ly-6 expression. Ly-6
      was localized intracellularly to the Golgi complex. The current results
      demonstrate that mature osteoblasts express on their cell surface specific Ly-6
      antigens in a pattern that distinguishes them from the surrounding bone marrow
      cells. These studies represent the first identification of osteoblast
      differentiation antigens that can be directly related to cells within the
      hematopoietic lineage. By identifying similar antigens, osteoblasts at various
      stages of differentiation may be identified, isolated, and characterized.

PMID- 7520862
TI  - Major species variation in the expression of galanin messenger ribonucleic acid
      in mammalian celiac ganglion.
AB  - To determine whether galanin may be a sympathetic neurotransmitter in the
      pancreas of primates and rats as well as dogs, the expression of the galanin gene
      was examined in the celiac ganglion of these species by in situ hybridization and
      RIA. Intense hybridization signal for galanin messenger RNA (mRNA) was observed
      in every neuronal cell body of the dog celiac ganglion. However, significant
      hybridization signal for galanin mRNA was seen in only 24 +/- 5% of celiac
      ganglion cell bodies in monkeys and was absent in rats. RIA of celiac ganglion
      extracts confirmed this species variation; galanin-like immunoreactivity was
      highest in dog celiac ganglion (158 +/- 13 pmol/g), present in monkeys (34 +/- 7
      pmol/g), and undetectable in rats (< 0.8 pmol/g). In contrast, the celiac ganglia
      of all three species showed intense hybridization signal for neuropeptide-Y (NPY)
      mRNA in the majority of neuronal cell bodies (dog, 82 +/- 4%; monkey, 92 +/- 2%;
      rat, 91 +/- 3%), and the celiac ganglion NPY immunoreactivity content was high in
      all three species (dog, 1064 +/- 155 pmol/g; monkey, 3180 +/- 745 pmol/g; rat,
      3412 +/- 347 pmol/g). Thus, there is a marked species variation in the expression
      of the galanin, but not the NPY, gene in the celiac ganglion of dogs, monkeys,
      and rats. These data suggest that galanin is an important sympathetic
      neurotransmitter in the pancreatic islets of dogs, but not those of primates or
      rats.

PMID- 7520860
TI  - Teicoplanin. A reappraisal of its antimicrobial activity, pharmacokinetic
      properties and therapeutic efficacy.
AB  - Since an earlier review in the Journal substantial additional data have
      accumulated, further clarifying the in vitro activity, pharmacokinetic profile,
      clinical efficacy and tolerability of teicoplanin. Recent therapeutic trials
      confirm the efficacy of teicoplanin in the treatment of microbiologically
      confirmed Gram-positive infections, including septicaemia, endocarditis, and
      infections of skin and soft tissue, bone and joints, and the lower respiratory
      tract. As teicoplanin can be administered once daily intramuscularly as well as
      intravenously, it has potential for outpatient treatment of severe Gram-positive
      infections. Teicoplanin is appropriate as treatment of patients with fever and
      neutropenia, but there is still controversy over the timing for introduction of
      glycopeptide antibiotics into therapeutic regimens. Teicoplanin is generally
      reserved for secondary therapy of patients with documented bacteraemia who fail
      to respond to initial empirical antibiotic regimens, but probably should be part
      of the initial empirical regimen in the setting of a high incidence of
      methicillin-resistant staphylococci. Teicoplanin has a lower propensity than
      vancomycin to impair renal function when either drug is combined with an
      aminoglycoside, causes fewer anaphylactoid reactions, and appears to be of
      comparable efficacy. Thus, teicoplanin may be preferred to vancomycin in the
      treatment of Gram-positive infections, and where a glycopeptide antibiotic is
      deemed a necessary inclusion in a regimen for empirical treatment in patients
      with fever and neutropenia.

PMID- 7520864
TI  - Anabolic effects of 3,3',5-triiodothyronine and triiodothyroacetic acid in
      cultured neonatal mouse parietal bones.
AB  - We previously reported that both T3 and triiodothyroacetic acid (Triac) stimulate
      bone resorption in organ culture, with Triac somewhat more potent than T3. In
      this study we compared the effects of T3 and Triac on DNA and protein synthesis
      in cultured neonatal mouse calvariae. After 24 h of preculture, with 72 h of
      treatment, but not 24 or 48 h, these hormones stimulated [3H]thymidine
      incorporation. After 72 h of preculture, stimulation was observed with only 24 h
      of treatment. These effects were significant at 10(-10) M and maximal at 10(-9) M
      for both T3 and Triac (treated/control ratios, 2.2 and 2.0, respectively). In
      contrast to their effects on bone resorption, T3 was more potent than Triac in
      stimulating [3H]thymidine incorporation. Insulin-like growth factor-binding
      protein-3 did not decrease the stimulation of DNA synthesis by T3 or Triac. The
      medium insulin-like growth factor-I concentration was less than 10(-10) M and was
      not regulated by these hormones. T3 and Triac stimulated [3H]proline
      incorporation into both collagen and noncollagen protein to a similar extent
      (approximately 30% at 10(-8) M). Indomethacin did not alter the effects of T3 and
      Triac on DNA or collagen synthesis. Aphidicolin, which blocked DNA synthesis
      completely, partially decreased the effects of thyroid hormones on collagen
      synthesis. The effect of aphidicolin on bone formation was less than that
      observed previously on bone resorption. We speculate that the effects of thyroid
      hormones on bone formation as well as bone resorption may be partially dependent
      on their mitogenic effects. As Triac is more potent in stimulating resorption and
      less potent in stimulating formation, Triac may be more catabolic than T3.

PMID- 7520863
TI  - Inhibition of nitric oxide synthase by NG-nitro-L-arginine causes a preferential
      decrease in pancreatic islet blood flow in normal rats and spontaneously diabetic
      GK rats.
AB  - To elucidate the effect of nitric oxide (NO) on the blood flow of the pancreatic
      islets, the NO synthase inhibitor NG-nitro-L-arginine (N-arg; 25 mg/kg BW) was
      administered iv to rats 10 min before pancreatic blood flow was measured with a
      nonradioactive microsphere technique. In male Sprague-Dawley rats, N-arg induced
      a marked decrease in islet blood flow (16 +/- 4 vs. 44 +/- 8 microliters/min.g
      pancreas; P < 0.001) and a less pronounced decrease in whole pancreatic blood
      flow (0.27 +/- 0.04 vs. 0.43 +/- 0.06 ml/min.g; P < 0.05), leading to a markedly
      decreased fractional islet blood flow (5.5 +/- 0.9% vs. 10.3 +/- 1.3%; P < 0.02).
      In a second experiment, injection of D-glucose (300 mg/kg BW, iv) in male Sprague
      Dawley rats induced a selective increase in islet blood flow (P < 0.05). Such an
      increase has previously been shown to be mediated by a vagal cholinergic
      mechanism. Administration of N-arg to these rats resulted in decreased pancreatic
      (P < 0.05), islet (P < 0.001), and fractional (P < 0.001) islet blood flow, which
      did not differ from those observed in normoglycemic rats after treatment with N
      arg. Furthermore, we studied the mechanism behind the previously described
      increase in islet blood perfusion, mediated by the vagus nerve, in F1-hybrids of
      the GK (Goto-Kakizaki) rat, a spontaneous animal model of noninsulin-dependent
      diabetes mellitus. Administration of N-arg to female GK rats resulted in
      decreases in islet (P < 0.001), pancreatic (P < 0.01), and fractional islet blood
      flow (P < 0.001) to the levels observed in female Wistar rats treated in
      parallel. These data are consistent with the possibility that NO is an important
      physiological regulator of islet blood flow. Furthermore, the vagally dependent
      high levels of islet blood flow demonstrated in the GK rat appear to be mediated
      by a mechanism involving NO.

PMID- 7520865
TI  - Recombinant insulin-like growth factor-II inhibits the growth-stimulating effect
      of growth hormone on the liver of Snell dwarf mice.
AB  - The actions and interactions of recombinant insulin-like growth factor-I and -II
      (IGF-I and IGF-II), alone or in combination with human GH on body growth and the
      growth of several organs were studied in the Snell dwarf mouse. IGF-I and -II
      stimulate to a similar extent sulfate incorporation into cartilage, and both IGFs
      increase body length and weight. IGF-II as well as IGF-I have clear effects on
      the size of the submandibular salivary glands, kidneys, and spleen. IGF-II,
      however, did not influence the weight of the lung, in contrast with IGF-I. GH
      treatment alone resulted in growth of the liver, whereas both IGFs were inactive.
      Surprisingly, IGF-II and, to a lesser extent, IGF-I inhibited GH-induced growth
      of the liver. Glycogen storage in the liver was decreased by treatment with IGF
      II alone or in combination with GH, as shown by histological examination. It was
      not affected by GH, IGF-I, or GH plus IGF-I. Also, the size of the centrilobular
      hepatocytes was decreased by treatment with IGF-II and IGF-II plus GH; GH alone
      had a hypertrophic effect, whereas IGF-I or GH plus IGF-I had none. In contrast
      to GH, IGFs did not increase polyploidy. Treatment with IGF-II increased the
      level of IGFBP-3, as did IGF-I or GH treatment, as shown by Western ligand
      blotting. The IGFs appeared to have a greater effect on the induction of 38.5
      kilodalton IGFBP-3 than GH, suggesting a different role in the regulation of
      glycosylation. In conclusion, IGF-I and IGF-II as well as GH have a stimulatory
      effect on general body growth and are effective in the stimulation of serum IGFBP
      3, sulfate incorporation into cartilage, as well as the growth of specific organs
      in Snell dwarf mice. Both IGFs, alone or in combination with GH, show distinct
      effects on the growth of the liver with respect to several histological
      parameters, which require further exploration.

PMID- 7520867
TI  - PTP-PEST: a protein tyrosine phosphatase regulated by serine phosphorylation.
AB  - The protein tyrosine phosphatase PTP-PEST is an 88 kDa cytosolic enzyme which is
      ubiquitously expressed in mammalian tissues. We have expressed PTP-PEST using
      recombinant baculovirus, and purified the protein essentially to homogeneity in
      order to investigate phosphorylation as a potential mechanism of regulation of
      the enzyme. PTP-PEST is phosphorylated in vitro by both cyclic AMP-dependent
      protein kinase (PKA) and protein kinase C (PKC) at two major sites, which we have
      identified as Ser39 and Ser435. PTP-PEST is also phosphorylated on both Ser39 and
      Ser435 following treatment of intact HeLa cells with TPA, forskolin or isobutyl
      methyl xanthine (IBMX). Phosphorylation of Ser39 in vitro decreases the activity
      of PTP-PEST by reducing its affinity for substrate. In addition, PTP-PEST
      immunoprecipitated from TPA-treated cells displayed significantly lower PTP
      activity than enzyme obtained from untreated cells. Our results suggest that both
      PKC and PKA are capable of phosphorylating, and therefore inhibiting, PTP-PEST in
      vivo, offering a mechanism whereby signal transduction pathways acting through
      either PKA or PKC may directly influence cellular processes involving reversible
      tyrosine phosphorylation.

PMID- 7520866
TI  - Exocrine granule specific packaging signals are present in the polypeptide moiety
      of the pancreatic granule membrane protein GP2 and in amylase: implications for
      protein targeting to secretory granules.
AB  - The mechanisms for segregation of secretory and membrane proteins incorporated
      into storage granules from those transported constitutively have been thought to
      be conserved in diverse cell types, including exocrine and endocrine cells.
      However, GP2, the major protein of pancreatic zymogen granule membranes, in its
      native glycosyl phosphatidylinositol (GPI)-linked form, is incorporated into
      secretory granules when expressed in exocrine pancreatic AR42J cells, but not in
      the endocrine cells such as pituitary AtT20. To determine whether the protein
      moiety of GP2 contains the cell-type specific information for packaging into
      granules, a secretory form of GP2 (GP2-GPI-), with the GPI attachment site
      deleted, was generated and introduced into AR42J and AtT20 cells. Like native
      GP2, GP2-GPI- localized to the zymogen-like granules of AR42J cells and underwent
      regulated secretion. In AtT20 cells expressing GP2-GPI-, however, the protein was
      secreted by the constitutive pathway. Thus, a granule packaging signal is present
      in the luminal portion of GP2 that is functional only in the exocrine cells.
      However, this cell-type dependent sorting process is not limited to GP2 or
      membrane proteins. Amylase, a major content protein of pancreatic acinar and
      serous salivary gland granules, was also secreted exclusively by the constitutive
      pathway when expressed in AtT20 cells. The cell-type specific targeting of GP2 to
      granules correlated with its behavior in an in vitro aggregation assay where it
      co-aggregated more effectively with content proteins from pancreatic zymogen
      granules than with those from pituitary granules.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7520868
TI  - Influence of left ventricular filling profile during preceding control beats on
      pulse pressure during ventricular premature contractions.
AB  - We investigated whether the left ventricular filling profile, defined as the
      early to late diastolic left ventricular filling volume ratio, during the
      preceding control beats actually affects the pulse pressure during a ventricular
      premature contraction (PVC). Twenty patients underwent invasive
      electrophysiological study for sinus bradycardia. VPCs with various coupling
      intervals were induced by right ventricular electrical stimulation, and the
      mitral filling flow velocity by pulsed Doppler echocardiography, the femoral
      arterial pressure curve and the electrocardiogram were simultaneously recorded.
      The early to late diastolic velocity-time integral ratio (Ei/Ai ratio) of the
      mitral filling flow velocity during the control beats which preceded the VPC was
      measured as an index characterizing left ventricular filling profile. The
      coupling interval of each VPC and the extrasystolic beat pulse pressure were
      measured. The ratio of the extrasystolic beat pulse pressure to the control beat
      pulse pressure was expressed in % (% extrasystolic beat pulse pressure). The
      correlation between the coupling interval and the % extrasystolic beat pulse
      pressure was investigated. Coupling intervals of 0.80, 0.70, 0.60, 0.50, and 0.45
      s were used. At a coupling interval of 0.80 or 0.45 s, the % extrasystolic beat
      pulse pressure showed no significant correlation with the Ei/Ai ratio. In
      contrast, the % extrasystolic beat pulse pressure with coupling intervals of
      0.70, 0.60, and 0.50 s showed a significant positive correlation with the Ei/Ai
      ratio (r = 0.67, 0.74, and 0.66, P < 0.01, respectively). In addition to the
      prematurity and the site of origin of the VPCs, the left ventricular filling
      profile during the preceding control beats may significantly affect the height of
      the pulse pressure during extrasystoles with medium length coupling intervals.

PMID- 7520869
TI  - Molecular analysis of a candidate gene for the reproductive isolation between
      sibling species of Drosophila.
AB  - The X-linked gene Hmr in Drosophila melanogaster, when mutated, rescues otherwise
      inviable interspecific hybrids from crosses between D. melanogaster and any of
      its three most closely related species D. simulans, D. mauritiana and D.
      sechellia. DNA from the site of a breakpoint at the putative locus of the gene
      has been cloned, and results of transcription and sequence analyses are
      presented. Three distinct mRNAs are transcribed from this locus, two of which are
      abundantly expressed throughout life. A third transcript, which is larger but
      rarer, appears to be disrupted by at least one of the two known mutations of Hmr.
      The gene encodes a mitochondrial ADP/ATP translocator protein, which plays an
      essential role in maintaining metabolic energy. Analysis of several cDNAs
      suggested that the rescue of hybrids may be dependent on mutations in the
      variable 3' end region of this gene, affecting the level and/or the stability of
      the largest messenger RNA.

PMID- 7520871
TI  - The mammary factor MPBF is a prolactin-induced transcriptional regulator which
      binds to STAT factor recognition sites.
AB  - Site-directed mutagenesis of the three binding sites for the mammary factor MPBF
      in the beta-lactoglobulin (BLG) promoter demonstrates that MPBF is a
      transcriptional activator of the BLG gene in mammary cells. MPBF requires
      phosphorylation on tyrosine for maximum binding activity and binds to GAS
      (interferon gamma-activation site) elements which are similar to the MPBF binding
      sites. Prolactin induces MPBF binding activity in CHO cells and is not
      antigenically related to Stat1 (p91) and Stat2 (p113), suggesting that this
      transcription factor is likely to be another member of the STAT family of
      cytokine/growth factor-induced transcription factors.

PMID- 7520870
TI  - The antiviral effect of keishi-ni-eppi-ichi-to, a traditional Chinese herbal
      medicine, on influenza A2(H2N2) virus infection in mice.
AB  - The antiviral effect of Keishi-ni-eppi-ichi-to (TJS-064), a traditional Chinese
      herbal medicine, was investigated in mice infected with influenza A2(H2N2) virus.
      When mice exposed to a 5 LD50 dose of the virus were treated orally with a 70
      mg/kg dose of TJS-064 1 day before and 1 day and 4 days after the infection, 100%
      survived over a 25-day experimental period. At the end of this period all the
      control mice, treated with saline alone, had died; their mean survival time in
      days (MSD) was 11.2 days. When mice infected with a 10 LD50 dose of the virus
      were treated with TJS-064, the MSD was > 17.4 days and there was a 50% survival
      rate, while the control group had a MSD of 8.7 days and a 0% survival rate. No
      significant antiviral effect of TJS-064 was observed when the agent was
      administered orally to mice infected with a 100 LD50 or larger dose of influenza
      virus. Pulmonary consolidations, virus titers in lung tissues and HAI titers in
      sera of infected mice treated with TJS-064 were all significantly lower than
      those of infected mice treated with saline. Interferon activities were detected
      in sera of mice treated with the agent at a dose of 100 mg/kg orally. Since
      viricidal and viristatic activities of the agent against influenza virus were not
      demonstrated, the antiviral effects of TJS-064 may be expressed through the
      host's antiviral functions including interferon production.

PMID- 7520872
TI  - Identification of imidazole as L-arginine-competitive inhibitor of porcine brain
      nitric oxide synthase.
AB  - Imidazole acts as a heme-site inhibitor of nitric oxide synthase (NOS). We used
      this compound to investigate whether the substrate L-arginine binds directly to
      the heme or to a separate domain of brain NOS. Enzyme kinetic experiments showed
      that imidazole enhanced the apparent Km for L-arginine without affecting maximal
      enzyme activity, and binding studies revealed that the inhibitor displaced the
      radioligand NG-nitro-L-[3H]arginine in a concentration-dependent fashion. These
      results demonstrate that imidazole exerts its effects on NOS in an L-arginine
      competitive manner and that the substrate site of the enzyme may be identical
      with the prosthetic heme group.

PMID- 7520873
TI  - Homology modelling and 1H NMR studies of human leukaemia inhibitory factor.
AB  - Human leukaemia inhibitory factor (LIF) is a glycoprotein with a diverse range of
      activities on many cell types. A molecular model of LIF has been constructed
      based mainly on the structure of the related cytokine granulocyte colony
      stimulating factor, and refined using simulated annealing and molecular dynamics
      in water. The model was stable during molecular dynamics refinement and is
      consistent with known stereochemical data on proteins. It has been assessed by
      comparison with 1H NMR data on the ionization behaviour of the six histidine
      residues in LIF, the imidazolium pKa values of which range from 3.6 to 7.4. These
      pKa values were assigned to individual histidine residues from NMR studies on a
      series of His-->Ala mutants. The environments of the histidine residues in the
      model account very well for their observed ionization behaviour. Furthermore, the
      model is consistent with mutagenesis studies which have defined a group of amino
      acid residues involved in receptor binding.

PMID- 7520874
TI  - Inhibition of reverse transcriptase of human immunodeficiency virus type 1 and
      chimeric enzymes of human immunodeficiency viruses types 1 and 2 by two novel non
      nucleoside inhibitors.
AB  - We have studied the effects of two non-nucleoside reverse transcriptase
      inhibitors (NNRTI), nitrophenyl phenyl sulfone (NPPS) and a potent derivative of
      oxathiin carboxanilide (UC-38), on enzymatically active molecular chimeras
      composed of complementary segments of the reverse transcriptases (RTs) of human
      immunodeficiency virus type 1 (HIV-1) and -2 (HIV-2). The substances inhibit only
      the DNA polymerase activity of HIV-1 RT with no effect on HIV-2 RT. The results
      suggest that there is a protein segment located between residues 158 and 190 that
      is critical for the inhibition by both compounds. However, there is probably a
      second segment that resides between residues 192 and 202, as in the case of NPPS,
      or residues 203 and 224, as in the case of UC-38, that is also crucial for the
      sensitivity of HIV-1 RT to both inhibitors.

PMID- 7520875
TI  - GRP78 induction by cyclosporin A in human HeLa cells.
AB  - Immunosuppressive drugs such as cyclosporin A (CsA) and FK506 are known to have
      pleiotropic effects on cells. Here we demonstrate that treatment of HeLa cells
      with low concentrations of CsA (but not of FK506) induces the synthesis of a
      stress protein, GRP78, located inside the endoplasmic reticulum. High
      concentrations of CsA lead to a general decrease in protein synthesis. When cells
      are stressed (heat-shocked) during the CsA treatment, the synthesis of heat shock
      proteins is reinforced. FK506 has no detectable effects at any concentration. The
      mechanism of induction of GRP78 by CsA remains presently unknown. Whatever the
      mechanism involved, GRP78 overexpression might be responsible for some of the
      physiological effects of CsA.

PMID- 7520876
TI  - Evidence that glucose increases monocyte binding to human aortic endothelial
      cells.
AB  - The rate of atherosclerosis is accelerated in humans with diabetes. The adhesion
      of monocytes to the vascular endothelium is a key event in the development of
      atherosclerosis. Alloxan (ALX)-induced diabetes in rabbits causes leukocyte
      accumulation on the arterial surface. However, the effect of glucose exposure on
      monocyte binding is not understood. We evaluated the effect of chronic elevated
      glucose on human monocyte binding to human aortic endothelial cells (HAEC) in
      culture. Monocyte binding to HAEC was significantly increased by chronic
      incubation of HAEC in high glucose for 7-10 days (CH-HG; 25 mM) compared with
      cells cultured for the same time in normal glucose (5.5 mM; CH-HG, 188 +/- 10
      cells/field vs. normal glucose, 111 +/- 7; P < 0.0005). Use of mannitol at a
      concentration to stimulate the hyperosmolar effects of glucose did not
      significantly alter monocyte binding. Acute 20-min exposure of HAEC to high
      glucose did not alter monocyte binding. The adherence of HL-60 cells, a
      neutrophil-like cell line, or human neutrophils was not induced by CH-HG culture.
      High glucose-induced monocyte binding was not associated with induction of the
      major endothelial cell adhesion molecules, including E-selectin, vascular cell
      adhesion molecule 1, and intercellular adhesion molecule 1 (ICAM-1). A monoclonal
      antibody TS1-18 to the beta 2 integrin component that is involved in binding to
      ICAM-1 on endothelial cells significantly reduced monocyte binding, whereas anti
      VLA-4 antibody was not effective. These results suggest that hyperglycemia can
      accelerate the rate of atherosclerosis in diabetics by increasing monocyte
      binding to the endothelium.

PMID- 7520877
TI  - Localization of thrombospondin, CD36 and CD51 during prenatal development of the
      human mammary gland.
AB  - Thrombospondin (TSP) is a 450 kDa extracellular matrix glycoprotein expressed in
      normal, hyperplastic, and neoplastic human breast. In this study, the patterns of
      expression of TSP were determined during development of the human fetal mammary
      gland between the 15th and the 39th week of gestation. Using
      immunohistochemistry, TSP is found in the dense mesenchyme immediately adjacent
      to the mammary bud, and at the membrane of budding epithelial cells invading the
      surrounding mesenchyme. As formation of the ductal tree system occurs, TSP is
      deposited at the myoepithelial-stromal junction of mammary ducts. Such an
      immunolocalization of TSP in buds and ducts of the fetal mammary gland has been
      confirmed at the mRNA level using in situ hybridization. Presence of TSP
      transcripts in nascent breast tissue has been also demonstrated by polymerase
      chain reaction assay. Comparison of TSP immunolocalization with that of two known
      TSP cell surface receptors, CD36 and CD51, reveals no codistribution of TSP with
      these receptors during mammary gland development. As opposed to TSP, CD36 is
      strongly expressed at the membrane of preadipocytes present in the fat pad
      tissue, but absent from budding epithelial cells. CD51 is only weakly expressed
      by malpighian epithelial cells and does not colocalize with TSP. In lactating
      ducts of a newborn, TSP disappears from the myoepithelial-stromal junction of
      ducts and is synthesized at the apices of secretory epithelial cells of lactating
      ducts together with CD36. In conclusion, our findings support the existence of an
      important role for TSP during development of the human fetal mammary
      gland.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520878
TI  - Transdifferentiation of embryonic and postnatal rabbit corneal epithelial cells.
AB  - In order to study the determination of corneal epithelial cells, rabbit corneal
      epithelium of 12- to 24-day embryos, newborn and 12-day-old offspring were
      recombined with mouse embryo upper-lip or dorsal dermis. Epithelial
      differentiation was analyzed using immunohistology with corneal monospecific
      monoclonal antibody AK12 (anti-keratin K12). Recombinants involving 12-day embryo
      undifferentiated corneal ectoderm formed a typical epidermis with hair follicles
      after 10 days of culture on the chick chorioallantoic membrane. Central corneal
      epithelium from 23- to 24-day embryos and newborn, which express suprabasally
      both K3 and K12 keratins and basally the K12 keratin alone, when grown in
      association with trichogenic dermis first failed to produce K12 in its new
      forming basal layer and then stratified after 11 days of culture above a
      differentiating epidermis with hair buds. When the culture period was increased
      up to 21 days by grafting under the kidney capsule from athymic mice, even the
      central corneal epithelium of 12-day-old off-spring gave rise to a complete
      epidermis with emerging hairs. The vibrissal- or pelage-type of hairs was in
      conformity with the regional origin of the mouse dermis. The species origin of
      the epithelial cells of the recombinants was discriminated incontestably using
      the Hoechst staining of interphase nuclei. Thus, the rabbit corneal epithelial
      cells can transdifferentiate into epidermal keratinocytes and trichocytes at
      least until 12 days after birth, despite the fact that from the fifth postnatal
      day the cells of its basal layer express both the K3 and the K12 keratins, a
      keratin pair marker of corneal cell-type terminal differentiation.

PMID- 7520879
TI  - Fibrogenic cytokines and connective tissue production.
AB  - The pathogenesis of fibrotic disorders is similar regardless of the tissues
      involved. Inflammatory leukocytes infiltrate the site triggered by chemotactic
      and activating mediators. This is followed by the elaboration of cytokines that
      directly and indirectly induce the proliferation of fibroblasts and endothelial
      cells and the deposition of extracellular matrix (ECM). In the absence of
      inhibitory signals, the continued production of these mediators sustains the
      connective tissue accumulation, which results in permanent alteration in tissue
      structure and function.

PMID- 7520880
TI  - [Interferons in multiple sclerosis].

PMID- 7520881
TI  - Kinetic parameters of desulfuration and dearylation of parathion and chlorpyrifos
      by rat liver microsomes.
AB  - Parathion and chlorpyrifos are phosphorothionate insecticides, but parathion is
      substantially more toxic than chlorpyrifos to rats, and both are more toxic to
      females than to males. A kinetic analysis of cytochrome P-450 mediated
      desulfuration (activation) and dearylation (detoxication) of the two insecticides
      indicated that rat hepatic microsomes have a higher capacity to activate and a
      lower capacity to detoxify parathion than chlorpyrifos; these capacities
      correspond to their acute toxicity levels. Greater capabilities of both
      activation and detoxication were found in males than in females for both
      insecticides, which is especially apparent by comparing the clearance terms
      (Vmax/Km). Since dearylation clearances, but not desulfuration clearances,
      correspond with the sex differences in toxicity levels of the two compounds,
      dearylation may be the more important factor in determining the acute toxicity
      level. An extrapolation of lethal dose levels of the two insecticides to
      concentrations that could be encountered in a severe intoxication indicated that
      activation of both insecticides could readily occur; however, the dearylation of
      chlorpyrifos, but not of parathion, would occur readily. This difference in the
      likelihood of dearylation could be an important contributor to the lower acute
      toxicity levels of chlorpyrifos.

PMID- 7520882
TI  - Interleukin-4 inhibits proliferation of human leukemic megakaryoblast cell line
      MHH 225.
AB  - The effects of six recombinant human cytokines: erythropoietin, GM-CSF, G-CSF,
      interleukin-3, -4 and -6 on the proliferation and differentiation of a human
      multilineage myeloid leukemia cell line MHH 225, established from the bone marrow
      of an AML(M7) patient in our laboratory determined by changes in antigen
      expressions using monoclonal antibodies in APAAP technique were examined in
      liquid suspension culture. The MHH 225 cells have been growing exponentially
      without cytokines or conditioned media. About 90 per cent of MHH 225 cells are
      CD33+ CD34+ CD3- CD7- CD19- CD20- TdT- with 57.6 per cent, 28.3 per cent and 7.8
      per cent of them being CD41+, glycophorin A+ and CD15+, respectively. After five
      days of treatment with erythropoietin, GM-CSF, G-CSF or IL-6 no change was
      observed in MHH 225 cell antigens expression. IL-3 (100 U/ml) induced a moderate
      increase in only CD13 and alpha naphthyl esterase positive cells from 6.5 +/- 1.9
      per cent and 5.7 +/- 2.4 per cent in control cultures to 21.6 +/- 3.0 per cent
      and 19.1 +/- 2.8 per cent, respectively. On the other hand, 100 U/ml IL-4
      significantly increased the number of CD13, CD15 and alpha naphthyl esterase
      positive cells to 48.9 +/- 5.0 per cent, 47.2 +/- 3.6 per cent and 46.1 +/- 3.0
      per cent, p < 0.001, respectively. Also, 100 U/ml IL-4 decreased the number of
      CD41 positive cells from 57.6 +/- 2.8 per cent to only 25.9 +/- 3.6 per cent and
      did not change the number of CD33 or glycophorin A positive cells. The present
      results showed that out of the six myelopoietic growth factors tested, IL-4 was
      the only one to inhibit selectively the proliferation of CD33+ CD41+ leukemic
      megakaryoblast cells suggesting that IL-4 may have a lineage regulatory effect in
      favour of a myeloblastic CD33+ CD13+ CD15+ at the expense of a megakaryoblastic
      CD33+ CD41+ amplification in human leukemia cells and with apparently no effect
      on leukemic erythroblast cells. The MHH 225 cell line provides a useful tool and
      freely available model to scientists for studying signal transduction via IL-4
      and for studies of 'lineage switch'.

PMID- 7520883
TI  - The role of CD40 and its ligand in the regulation of the immune response.

PMID- 7520884
TI  - Molecular pathology of X-linked immunoglobulin deficiency with normal or elevated
      IgM (HIGMX-1).

PMID- 7520885
TI  - Antisperm antibody-mediated alterations in the cellular activity of human
      trophoblast cells in culture.
AB  - Immune recognition of the fetus is well documented, yet the immunological basis
      of pregnancy loss awaits elucidation. Identification of trophoblast membrane
      epitopes as non-self either by preformed immunoglobulins or by circulating
      immunocompetent cells would lead to immunological rejection of the tissue. Such
      an event may occur in cases of cross-reacting antibodies developed as a
      consequence of exposure of sperm surface antigens. This hypothesis was tested by
      developing specific antibodies in rabbits against intact sperm surface antigens.
      These were subjected to different schedules of IgG purification and
      characterization. By means of nuclide precursor incorporation, the effect of
      antisperm antibody on DNA, RNA and protein synthesis of trophoblast cells in
      culture were studied. The results showed that the antibody inhibits incorporation
      into cells but after a delay of 72 hours some cells gradually recover. The
      interaction also led to a reduced rate of hCG production. Lysosomal enzyme
      activity was inhibited in the spent medium of antibody-treated cells but lysosome
      rich fractions showed no effect. This indicated that the major effect of the
      antibody was growth inhibitory rather than cytolytic.

PMID- 7520886
TI  - Toxicity of 1,3-butadiene to bone marrow mimics haematopoietic defects observed
      in mice bearing white spotted or steel mutations.
AB  - In order to clarify the role of haematopoietic stem and progenitor cells in bone
      marrow toxicity induced by 1,3-butadiene, we examined the effects of its primary
      metabolite, 3,4-epoxybutene, on the cytokine response of these cells from C57B1/6
      mice. Pretreatment with epoxybutene in vitro suppressed recombinant interleukin-3
      stimulated colony formation in haematopoietic stem and progenitor cells, had no
      effect on colony formation with recombinant granulocyte/macrophage-colony
      stimulating factor or recombinant granulocyte-colony stimulating factor alone,
      and completely blocked the synergism of recombinant c-kit ligand and
      granulocyte/macrophage colony stimulating factor. Butadiene-induced
      leukaemogenesis, macrocytic anaemia and thymic atrophy are reminiscent of the
      conditions observed in mice bearing mutations at the W or Sl loci, which are
      deficient in the c-kit receptor and c-kit ligand, respectively. Epoxybutene did
      not suppress colony formation in cells from W/Wv and Sl/Sld mice, consistent with
      the absence of the population of haematopoietic stem and progenitor cells that is
      susceptible to butadiene in those genetically deficient strains. These findings
      indicate that the pathological conditions observed after either exposure to
      butadiene or W or Sl mutations are due to a functional defect in a subpopulation
      of primitive haematopoietic stem and progenitor cells that plays a major role in
      the pathogenesis of both T-cell leukaemia/lymphoma and anaemia in the mouse.

PMID- 7520887
TI  - Glial hypertrophy is associated with synaptogenesis following motor-skill
      learning, but not with angiogenesis following exercise.
AB  - Rats reared from weaning in a complex environment have an increase in 1) glial
      surface area, 2) capillary volume, and 3) the number of synapses, per neuron. In
      that paradigm it has not been possible to determine whether the glial increase
      more closely correlates with the increase in synaptic numbers or with
      angiogenesis. More recently we have found that rats that exercised had an
      increase in the density of capillaries without an increase in the synaptic
      numbers, whereas rats that learned new motor skills had a greater number of
      synapses per neuron without an increase in the density of capillaries. Those
      findings provided the opportunity to investigate whether changes in glial volume
      in the cerebellum correspond to changes in the number of synapses or in capillary
      volume. Glial area fraction estimates were obtained using point counts on
      electron micrographs from the previous studies. The skill learning group had a
      greater volume of molecular layer per Purkinje cell, and also a greater volume of
      glia per Purkinje cell, than rats in either an inactive group or rats in two
      exercise groups. No significant differences were found in glial volume per
      synapse and glial volume per capillary across groups, although there was a
      tendency for glial volume per capillary to be lower in the exercise groups. The
      data indicate that glial volume correlates with synaptic numbers and not with
      capillary density.

PMID- 7520888
TI  - Histochemical and morphological studies on Trichinella spiralis larvae treated
      with high hydrostatic pressure.
AB  - Histochemical and morphological observations were made on Trichinella spiralis
      larvae treated with hydrostatic pressures of 100, 150, 200 and 300 MPa using
      hematoxylin-eosin (HE), periodic acid-Schiff (PAS) and Azan staining. Few
      histochemical changes were observed in HE and PAS stained larvae after
      pressurization at 200 MPa and under. However, red staining by Azan changed to
      blue in the anterior stichosome of larvae and skeletal muscle of mice, when the
      hydrostatic pressure was raised from 150 to 300 MPa. At 150 and 200 MPa,
      boundaries among stichocytes were indistinct or irregular, and unstained areas
      were observed in stichocytes of larvae using Azan staining. At 300 MPa, all
      tissues of larvae and mouse muscle stained blue with Azan. At the same pressure,
      decrease in PAS positive staining of stichocytes and dilation of muscular cells
      were observed in larvae. It is assumed that these histochemical and morphological
      changes in pressurized larvae might be related to the loss of infectivity of
      larvae.

PMID- 7520889
TI  - Novel psi-S-CH2 peptide-bond replacement and its utilization in the synthesis of
      nonpeptidic surrogates of the Leu-Asp-Val sequence that exhibit specific
      inhibitory activities on CD4+ T cell binding to fibronectin.
AB  - The Leu-Asp-Val-(LDV)-containing amino acid sequence, derived from the
      alternatively spliced first connecting segment region of fibronectin (FN), was
      shown to be recognized primarily by the alpha 4 beta 1-integrin receptor
      expressed on the surface of various cell types. This adhesion epitope may
      therefore inhibit integrin-mediated cell interactions with the extracellular
      matrix glycoprotein, including adhesion, migration, activation and
      differentiation. To probe the structural requirements for LDV recognition by
      integrins and examine the feasibility of inhibition of LDV-dependent cell-FN
      interactions, we have designed and constructed a novel psi-S-CH2 peptide bond
      surrogate that was employed in the formation of LDV surrogates. The synthesis of
      the psi-S-CH2 surrogates reported herein is based on Michael addition of 4
      methylpentane thiol to an itaconic acid diester to form an S-CH2 bond. We have
      found that the LDV surrogates comprises of 4-methylpentanoate-Asp-i-butyl amide
      and 8-methyl-3-(2-methylpropylaminocarbonyl)-5-thianonanoic acid interfered with
      CD4+ human T-cell adhesion to FN in vitro, with an ED50 of 280 micrograms/mL. A
      control structural mimetic of the Leu-Glu-Val (LEV) peptide did not interfere
      with the T-cell-FN interaction. The specificity of the reaction was substantiated
      by the finding that the LDV mimetics did not interfere with T-cell adhesion to
      laminin, another major cell-adhesive glycoprotein of the extracellular
      matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520890
TI  - Efficacy of the hematoregulatory peptide SK&F 107647 in experimental systemic
      Candida albicans infections in normal and immunosuppressed mice.
AB  - SK&F 107647, a novel synthetic dimeric pentapeptide, has been shown to be a
      potent hematoregulatory agent. The potential for the hematoregulatory factors
      elicited by SK&F 107647 to confer protection in experimental models of systemic
      Candida albicans infection was evaluated in immunosuppressed and immunocompetent
      mice. Prophylactic treatment with recombinant human interleukin-1 (rhIL-1),
      recombinant human granulocyte colony stimulating factor (rhG-CSF), or the
      hematoregulatory peptide SK&F 107647 significantly increased survival times in
      gamma irradiated immunosuppressed as well as non-irradiated immunocompetent mice
      challenged with a lethal dose of C. albicans. Protection was also observed in
      athymic nu/nu "nude" mice. Additionally, significant increases in survival in non
      irradiated immunocompetent mice dosed by oral gavage were observed. These results
      indicate that SK&F 107647 can significantly enhance natural host resistance to
      experimental C. albicans infections both in immunosuppressed and immunocompetent
      mice.

PMID- 7520891
TI  - [Anhidrotic ectodermal dysplasia. Disorder of the differentiation of hair
      follicles and sweat glands leads to abnormal keratinization].
AB  - We report on an 11-year-old female patient with anhidrotic ectodermal dysplasia
      (AED) showing the following characteristics: (1) reduced number of hair follicles
      and incomplete formation of sweat glands; (2) disturbed hair growth with
      shortening of anagen and anhidrosis; (3) disturbed cytokeratin expression pattern
      of CK 13, 14, 19 (follicular epithelium) and of CK 18 (eccrine sweat glands); (4)
      reduction of cystine and increase in sulphonic cysteine acid. Thus, we
      demonstrated pathological differentiation on the immunomorphological and on the
      biochemical level, leading to disturbed keratinization that could be visualized
      by transmission and scanning electron microscopical studies of the hair shafts.
      According to these findings AED is a developmental defect that involves not only
      incomplete formation of hair follicles and sweat glands but also a disordered
      differentiation and follicular keratinization with disturbed cytokeratin pattern
      and pathological amino acid composition of the terminal hairs produced.

PMID- 7520892
TI  - CD44 variant isoforms are preferentially expressed in basal epithelial of non
      malignant human fetal and adult tissues.
AB  - CD44 is a transmembrane glycoprotein, which can exist in a multitude of isoforms
      due to alternative splicing of the pre-mRNA. We have generated monoclonal
      antibodies to several of these variant regions, which are encoded by 10
      additional exons in the extracellular part of the molecule. CD44 variant isoforms
      have been reported to be involved in the malignant progression of rat and human
      tumours. The precise localization of CD44 variant isoforms in normal
      developmental and morphogenetic processes is essential for diagnostic studies of
      human tumorigenesis. Therefore, we have analysed a large number of different
      human tissues by immunohistochemistry for the expression of CD44 isoforms
      containing either exons 4v, 6v or 9v. Expression of exon 9v-isoforms was detected
      in almost all epithelia analysed, with a few exceptions. Exon 6v isoforms are
      expressed only in squamous and glandular epithelial, e.g. skin epidermis, sweat
      and sebaceous glands, oesophagus, ducts of the mammary gland, salivary and
      prostate glands. Detection of exon 4v-encoded isoforms was restricted to the
      epidermis and the oesophagus. Similar tissue distributions of CD44 variant
      isoforms were observed in 10-week-old fetal tissues. Since one of the ligands of
      CD44 is hyaluronic acid (HA), we also analysed the tissue distribution of HA
      synthetase. HA synthetase was detected in all tissues analysed, showing good
      correlation with the expression of the standard form of CD44, CD44s.

PMID- 7520893
TI  - [Are tip links the basis for mechanosensitivity of hair cells?].
AB  - The singular sensitivity of cochlear outer hair cells suggests an extremely
      efficient exploitation of the energy supplied by the mechanical stimulus. If,
      however, the transduction channels were located at one end of the hair bundle's
      tip links, not more than 1/250 of the stimulus energy could be used to change the
      open probability of the channels. Furthermore, the mechanosensitive nematocytes
      of Hydra vulgaris possess a sensory hair bundle with horizontal links and have a
      transduction mechanism with functional properties similar to those of hair cells,
      even though tip links are absent between stereocilia. Therefore, I propose that
      the transduction channels of hair cells are connected to the short row-to-row
      horizontal links at the distal ends of neighboring stereocilia. These links, as
      well as the tip links, are oriented in accordance with the directionality of hair
      cell mechanosensitivity. The elastic elements connected with the horizontal links
      receive a larger part of the stimulus energy than the tip links. Since the short
      horizontal links resemble rigid rods rather than "spare springs", the points of
      insertion of these links in the stereocilia (i.e., the transduction channels)
      must move a distance upsilon parallel to the longitudinal axis of the
      stereocilium when the hair bundle is deflected by an angle phi. Computation shows
      that upsilon is proportional to phi. In the stereocilium, elastic elements
      ("gating springs") connect the cytoskeleton and transduction channel. The force
      in the gating springs that is counteracting the movement of the transduction
      channels may be varied in the process of adaptation by an active motor, as has
      been proposed in other investigations.

PMID- 7520894
TI  - [The incurable tumor patient].
AB  - In patients suffering from advanced or recurrent cancers that are no longer
      amenable to curative treatment, palliation and symptomatic care have to take the
      place of cure. In such cases, palliation aims at relief of pain, alleviation of
      functional disabilities and restoration of mental and social balance. Since the
      clinicians effort is concentrated on the control of symptoms of uncontrollable
      disease, decisions have to be made concerning the relative value of the various
      methods available for treatment and support in the individual patient. Criteria
      for the physician's decision-making are important parameters in any approach to
      the patient with incurable cancer and have particular significance in caring for
      terminal disease.

PMID- 7520895
TI  - T cells recognize a peptide derived from alpha-gliadin presented by the celiac
      disease-associated HLA-DQ (alpha 1*0501, beta 1*0201) heterodimer.
AB  - CD is unique among the HLA-associated diseases since (a) the disease-promoting
      agent (gliadin) is known and (b) the disease is precipitated mainly in
      individuals carrying a particular cis- or trans-encoded HLA-DQ heterodimer; i.e.,
      DQ(alpha 1*0501, beta 1*0201). Further, a preponderance of gliadin-specific T
      cells derived from the small intestinal mucosa of CD patients are restricted by
      this DQ heterodimer. T-cell recognition of gliadin peptides presented by the
      DQ(alpha 1*0501, beta 1*0201) heterodimer may thus be of importance in CD. Here
      we report that a T-cell clone from a patient with CD recognizes a synthetic alpha
      gliadin peptide, when presented by the cis- or trans-encoded CD-associated
      DQ(alpha 1*0501, beta 1*0201) heterodimer. The minimal peptide recognized by the
      T-cell clone corresponds to residues 31-47 of alpha-gliadin, which is included in
      the part of alpha-gliadin previously shown to have disease-promoting activity.
      When testing analogue peptides derived from other alpha-gliadin sequences, one
      peptide differing by one amino acid was recognized by the T-cell clone, whereas
      the other peptide differing by two amino acids was not recognized. Our findings
      demonstrate that the CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer may
      serve as an antigen-presenting molecule to T cells for certain gliadin peptides.

PMID- 7520896
TI  - HLA-DR alpha chain residues located on the outer loops are involved in
      nonpolymorphic and polymorphic antibody-binding epitopes.
AB  - The structure-function relationships of the HLA-DR alpha chain have been analyzed
      by identifying DR alpha residues involved in several nonpolymorphic and
      polymorphic antibody epitopes. Antibody binding to transfectants expressing a WT
      or mutant DR alpha chain with the WT DR(beta 1*0701) chain was analyzed. Our
      results indicate that residues 18, 36, and 39 located on the outer loops of the
      DR alpha chain are critical for one or more of the epitopes recognized by the
      SG157, Q2/70, L243, LB3.1, D1-12, and CL413 mAbs. Similar results were obtained
      when the DR alpha position 18 and 39 mutants were expressed with other DR beta 1
      alleles. Furthermore, residues 15 and 18 of the DR alpha chain were shown to be
      involved in the epitopes of two polymorphic mAbs, HU-26 and I-2, whose epitopes
      also include residue 4 of the corresponding DR beta chains. In addition to their
      involvement in antibody-binding epitopes, residues in this region on the outer
      surface of the DR alpha chain have also been shown to be involved in superantigen
      binding and presentation and T-cell recognition of foreign antigen, emphasizing
      the functional importance of DR alpha-chain residues located outside of the
      peptide-binding groove.

PMID- 7520897
TI  - Epitope specificity of HLA class I alloantibodies. I. Frequency analysis of
      antibodies to private versus public specificities in potential transplant
      recipients.
AB  - Sera obtained sequentially from 419 patients awaiting solid organ transplantation
      were screened and analyzed for HLA class I epitope specificity. Antibodies
      detected in each serum were defined as "private" if reactivity could only be
      demonstrated against a single specificity within one of the eight major CREGs, or
      as "public" if reactivity in a serum could be demonstrated against two or more
      specificities within a single CREG. A total of 139 sera contained % PRA > 0, in
      which 147 specific antibodies were identified. Of the 103 positive sera, 93 (90%)
      contained antipublic antibodies, with or without additional antiprivate
      antibodies, whereas just 10 (10%) sera contained only apparent antiprivate
      antibodies. The success rate in defining antibody specificities was low at PRA
      values of 1%-20% due to weak reactivity and high false-positive rates.
      Specificity analysis with high test sensitivity and specificity was achieved with
      PRA values between 40% and 80%. At PRA values > 80%, test sensitivity remained
      high but specificity declined. We conclude that most anti-HLA antibodies are
      directed against high frequency public epitope clusters (CREGs), and highly
      sensitized patients develop antibodies in a fairly predictable fashion, a feature
      that significantly improved the success rate of specificity analysis. Since high
      frequency antipublic antibodies are common sequelae of CREG mismatches, further
      definition of HLA class I public epitopes eventually may be important in donor
      recipient matching.

PMID- 7520899
TI  - The mniopetals, new inhibitors of reverse transcriptases from a Mniopetalum
      species (Basidiomycetes). I. Producing organism, fermentation, isolation and
      biological activities.
AB  - Six novel enzyme inhibitors of RNA-directed DNA-polymerases of human
      immunodeficiency-, avian myeloblastosis and murine leukemia viruses were isolated
      from fermentations of a canadian Mniopetalum species. They were named mniopetals
      A, B, C, D, E and F. Their structures were elucidated by spectroscopic methods.
      The compounds, in addition to their inhibitory activities on reverse
      transcriptases, exhibit antimicrobial and cytotoxic properties.

PMID- 7520898
TI  - Inhibitory effect of recombinant fibronectin polypeptides on the adhesion of
      liver-metastatic lymphoma cells to hepatic sinusoidal endothelial cells and tumor
      invasion.
AB  - We have investigated the inhibitory mechanism of the initial arrest of L5178Y
      ML25 lymphoma cells in a target organ (liver) by using recombinant fibronectin
      fragments with cell- and/or heparin-binding domains (C-274, H-271 or the fusion
      fragment CH-271). Pretreatment of hepatic sinusoidal endothelial (HSE) cell
      monolayers with lymphoma cells or their conditioned medium for 4 to 6 h resulted
      in the enhancement of lymphoma cell adhesion to HSE cell monolayer. The increased
      tumor adhesiveness was completely abolished by preincubation of the conditioned
      medium with anti interleukin-1 beta monoclonal antibody (mAb). Synthetic sialyl
      Le(x) (SLe(x)) as a ligand for endothelial cell leukocyte adhesion molecule-1
      (ELAM-1) adhesion receptor and anti ELAM-1 mAb blocked the conditioned medium
      induced enhancement of tumor-endothelial cell interaction, while pretreatment of
      the activated HSE cell monolayer with anti vascular cell adhesion molecule-1
      (VCAM-1) mAb did not affect the enhanced tumor cell adhesion. These results
      indicate that tumor cell interaction with the stimulated HSE cells is mediated by
      ELAM-1 molecules on HSE cells. However, the expression of SLe(x) and SLe(a) on
      the tumor surface was not observed by flow cytometric analysis. ELAM-1-mediated
      enhancement of tumor cell adhesion to HSE monolayer was also inhibited in a
      concentration-dependent manner by CH-271 fusion polypeptide or the sulfated
      chitin derivative sulfated carboxymethyl-chitin, which can bind to the heparin
      binding domain of CH-271. In addition, CH-271 inhibited not only tumor
      endothelium interaction but also tumor cell invasion into reconstituted basement
      membrane Matrigel in vitro.

PMID- 7520900
TI  - Isolation and characterization of the major equilibrium product of FK-520.
AB  - The existence of an isomeric form in equilibrium with the major component of FK
      520 in polar solutions has been demonstrated. This minor component has been
      isolated in high yield and purity by a novel crystallization strategy and
      preparative HPLC. The equilibrium product was characterized by NMR and MS.

PMID- 7520901
TI  - Nicotinic acetylcholine receptor subunits expressed in rat cochlea detected by
      the polymerase chain reaction.
AB  - Poly(A)+ RNA was extracted from rat cochleae using guanidinium thiocyanate and
      oligo(dT)-cellulose, and converted into cDNA by reverse transcriptase using an
      oligo(dT) primer. Oligonucleotides complementary to conserved 5' and 3' regions
      of alpha and beta subunits of the neuronal nicotinic acetylcholine receptor
      subunit (nAChR) family were then used as primers to screen the cochlear cDNA via
      the polymerase chain reaction (PCR) procedure. PCR products of approximately 900
      bp length, purified by agarose gel electrophoresis, were nick translated to
      produce [32P]-dCTP labelled probes for Southern Blot screening of nAChR cDNAs. Of
      the four alpha and three beta subunits screened, only alpha 5 and beta 4 nAChR
      cDNAs hybridized. The alpha 5 PCR product was cloned and sequenced and proved to
      be identical to published sequence for alpha 5. The detection of alpha 5 and beta
      4 nAChR subunit expression in cochlear tissue supports previous
      electrophysiological and immunocytochemical evidence for nAChR-mediated
      centrifugal control of hearing function.

PMID- 7520902
TI  - AChE-staining of type II ganglion cells, processes and terminals in the cochlea
      of the mustached bat.
AB  - There have been a number of reports showing that ganglion cells of sensory
      neurons may be stained by traditional acetylcholinesterase (AChE) histochemical
      techniques commonly used to demonstrate efferent nerve fibers and terminals. AChE
      staining has been described for cell bodies in the vestibular and spiral ganglia;
      staining of peripheral and central processes, however, is rare and the presence
      of reaction product in afferent terminals has not been reported. The outer hair
      cells of mustached bats, Pteronotus parnellii, differ from those of most mammals
      in that they typically have a single, large efferent terminal surrounded by 5-7
      small, afferent terminals. In this animal an AChE-positive reaction was found not
      only in efferent fibers and terminals but also in type II ganglion cells, their
      peripheral and central processes and in outer hair cell terminals. The stained
      cell bodies were smaller than the unstained type I ganglion cells and they were
      much fewer in number. The processes of the stained cells could be followed from
      the soma. The central processes were dispersed throughout the VIIIth nerve trunk.
      Stained peripheral processes were evident in the osseous spiral lamina, floor of
      the tunnel of Corti and first space of Nuel and in the outer spiral plexus along
      the sides of the outer phalangeal (Deiters') cells. AChE-stained afferent
      terminals were easy to identify after transection of the crossed olivocochlear
      bundle (COCB) and subsequent degeneration of large efferent terminals. These
      results are of interest in that assessments of efferent nerve histochemistry
      after COCB transection need to recognize the potential contribution of AChE
      reaction product in afferent terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520903
TI  - The pharmacokinetics of risperidone in humans: a summary.
AB  - Risperidone is rapidly and completely absorbed after oral administration; less
      than 1% is excreted unchanged in the feces. The principal metabolite was found to
      be 9-hydroxyrisperidone. Hydroxylation of risperidone is subject to the same
      genetic polymorphism as debrisoquine and dextromethorphan. In poor metabolizers
      the half-life of risperidone was about 19 hours compared with about 3 hours in
      extensive metabolizers. However, becuase the pharmacology of 9-hydroxyrisperidone
      is very similar to that of risperidone, the half-life for the "active fraction"
      (risperidone +9-hydroxyrisperidone) was found to be approximately 20 hours in
      extensive and poor metabolizers. We found that risperidone exhibited linear
      elimination kinetics and that steady state was reached within 1 day for
      risperidone and within 5 days for the active fraction.

PMID- 7520904
TI  - Efficacy of risperidone on positive features of schizophrenia.
AB  - Dopaminergic hyperactivity mediated via D2 receptors is implicated in the
      etiology of positive symptoms of schizophrenia, but selective D2 antagonists
      provide imperfect therapy. This article describes a subanalysis of a trial of
      risperidone, a combined 5-HT2A/D2 antagonist, in 513 patients with DSM-III-R
      chronic schizophrenia. Risperidone at 2, 6, 10, and 16 mg/day was compared with
      placebo and haloperidol 20 mg/day. All doses of risperidone and the 20-mg dose of
      haloperidol were superior to placebo (mean change from baseline on the PANSS
      positive and general psychopathology subscales). The 6-mg dose of risperidone
      also produced significantly more improvement than haloperidol 20 mg. We conclude
      that risperidone is an effective drug for patients with positive features of
      schizophrenia.

PMID- 7520905
TI  - Negative symptoms in schizophrenia: assessment of the effect of risperidone.
AB  - This article reviews the definitions of negative symptoms and the deficit
      syndrome of schizophrenia, rating scale criteria (the Scale for Assessment of
      Negative Symptoms and the Positive and Negative Syndrome Scale), Crow's Type II
      syndrome, and Carpenter's deficit syndrome in relation to the DSM-IV. The
      effectiveness of conventional neuroleptics against negative symptoms is still in
      question. Improvement in negative symptoms may occur in tandem with improvement
      in the florid symptoms of schizophrenia, but negative symptoms may be difficult
      to discriminate from the extrapyramidal side effects that are caused by
      conventional neuroleptics. In a multicenter trial comparing the novel
      antipsychotic risperidone with haloperidol and placebo in symptomatic
      schizophrenia, negative symptoms (assessed using the Positive and Negative
      Syndrome Scale) were reduced more by risperidone at a dose of 6, 10, and 16
      mg/day than by placebo. Haloperidol at a dose of 20 mg/day was not significantly
      better than placebo. Risperidone 6 mg was the lowest dose that produced
      substantial change in negative symptoms and no increase in extrapyramidal
      symptoms and antiparkinsonian medication use.

PMID- 7520906
TI  - Extrapyramidal side effects and tolerability of risperidone: a review.
AB  - The effectiveness of conventional neuroleptics in schizophrenia is often limited
      by extrapyramidal side effects (EPS), which are known to contribute to poor
      compliance and relapse. However, there is now evidence that drugs that block 5
      HT2 receptors as well as D2 receptors have better EPS profiles. Risperidone has
      these pharmacologic properties. In two large clinical trials, risperidone (2, 6,
      10, 16 mg/day or 4, 8, 12, 16 mg/day) was compared with either placebo and
      haloperidol (20 mg/day) or risperidone (1 mg/day) and haloperidol (10 mg/day).
      Extrapyramidal side effects were assessed using the Extrapyramidal Symptom Rating
      Scale and by recording the use of anticholinergic medication. Other adverse
      effects were assessed using the UKU Side Effects Scale. In both studies, the
      severity of EPS in the risperidone groups was significantly less than in the
      haloperidol group. In the placebo-controlled study, doses of 2 and 6 mg/day of
      risperidone produced no worse EPS than placebo. Other side effects were minor,
      and included brief hypotension (mediated via alpha-blockade) and weight gain.
      Overall, risperidone at antipsychotic doses was better tolerated than
      haloperidol.

PMID- 7520907
TI  - Risperidone: new horizons for the schizophrenic patient. 9th World Congress of
      Psychiatry of the World Psychiatric Association, Rio de Janeiro, June 1993.

PMID- 7520908
TI  - Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism,
      receptor occupancy profile, and pharmacologic activity.
AB  - The interaction of risperidone, 9-hydroxyrisperidone (the principal active
      metabolite), and clozapine with neurotransmitter receptors was investigated in
      vitro using animal brain tissue homogenates and cloned human receptors expressed
      in cells and ex vivo using quantitative receptor autoradiography in rat and
      guinea pig brain sections. In vitro, risperidone and 9-hydroxyrisperidone had
      similar binding profiles, and their highest affinity was for 5-HT2A receptors
      (cloned human, Ki 0.4 nM); affinities for other 5-HT-receptor subtypes were at
      least 100 times lower. Risperidone bound to 5-HT2A receptors with 20 times
      greater affinity than clozapine and 170 times greater affinity than haloperidol.
      Clozapine primarily bound to histamine H1 receptors and haloperidol to dopamine
      D2 receptors. The binding affinity of risperidone and 9-hydroxyrisperidone for
      the D2 family of receptors (D2L, D2S, D3, D4) was one order of magnitude lower
      than their affinity for 5-HT2A receptors. Risperidone bound to D2 and D3
      receptors with 50 and 20 times greater affinity than clozapine and was only 2 to
      3 times less potent than haloperidol. All compounds bound with similar affinities
      to D4 receptors (Ki 5-9 nM), and their affinities for D1 receptors were 100 times
      lower than for D4 receptors. The ex vivo receptor occupancy profile of the
      compounds matched the in vitro receptor binding profile. A conspicuous property
      of risperidone, not seen for the other compounds, was the shallow occupancy curve
      at D2 receptors in the striatum and mesolimbic brain area. Moreover, it was
      observed that antagonism of strong D2-receptor stimulation by apomorphine in rats
      was achieved at less than 50% D2 occupancy by the antipsychotics.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7520909
TI  - Structurally distinct disintegrins contortrostatin and multisquamatin
      differentially regulate platelet tyrosine phosphorylation.
AB  - Tyrosine phosphorylation of multiple platelet proteins is regulated by the
      integrin alpha IIb beta 3. In order to further examine integrin-regulated
      tyrosine phosphorylation, we have used small Arg-Gly-Asp-containing snake venom
      proteins (termed disintegrins) that inhibit platelet aggregation to competitively
      block the agonist-induced binding of fibrinogen to alpha IIb beta 3. One
      structurally unique disintegrin, contortrostatin (which appears to be a disulfide
      linked dimer of 13.5 kDa with two Arg-Gly-Asp sites), was found to trigger
      signaling events typically mediated by fibrinogen cross-linking of alpha IIb beta
      3, as demonstrated by tyrosine phosphorylation of the tyrosine kinase pp72syk and
      a 140-kDa protein. Contortrostatin and another disintegrin, multisquamatin (a
      monomer of 5.7 kDa with a single Arg-Gly-Asp site), did not affect thrombin
      induced platelet shape change, secretion, or integrin-independent tyrosine
      phosphorylation; however, they inhibited aggregation and aggregation-dependent
      tyrosine phosphorylation of numerous proteins, including the focal adhesion
      kinase pp125FAK. Our results suggest that structurally distinct disintegrins have
      varying effects on tyrosine phosphorylation; while monomeric multisquamatin and
      dimeric contortrostatin both inhibit aggregation-dependent tyrosine
      phosphorylation, contortrostatin also possesses a unique functional activity that
      allows it to activate an intracellular signaling pathway leading to tyrosine
      phosphorylation. This activity may be involved in the function of this snake
      venom protein on hemostasis.

PMID- 7520910
TI  - Identification of an epitope in the substance P receptor important for
      recognition of the common carboxyl-terminal tachykinin sequence.
AB  - The substance P receptor and the anti-substance P antibody NC1 share the ability
      to bind to the COOH terminus of substance P. Sequence analysis identified a
      direct noninterrupted homology of 5 residues in the two molecules. Replacement of
      Gly166 and Tyr167 in this epitope of the substance P receptor by the
      corresponding substance K receptor amino acids (Cys and Phe) increases the
      affinity toward substance P 2-fold and toward substance K and neurokinin B 11-
      and 21-fold, respectively. A significantly larger effect of the mutation is
      observed for the hexapeptides of substance P and substance K which show a
      mutation-induced increase in binding energy of more than 2 kcal/mol. Hence, the
      NH2 terminus of substance P and, to a lesser extent, of substance K masks the
      effect of the mutation. I conclude that the epitope is important for recognition
      of the common COOH terminus of the tachykinins and for preservation of
      selectivity. The data furthermore suggest that formation of the peptide-receptor
      complex occurs through a composite set of interactions which are not adequately
      described by the two-site/no cooperativity "address-message" model.

PMID- 7520911
TI  - Catalytic subunit of protein kinase A induces amylase release from streptolysin O
      permeabilized parotid acini.
AB  - Amylase release from parotid acinar cells is a typical model of cAMP-mediated
      exocytosis. To obtain unequivocal data concerning the role of cAMP-dependent
      protein kinase (PKA) in amylase exocytosis, we undertook the direct introduction
      of the PKA catalytic subunit into the parotid acini by permeabilization with
      streptolysin O (SLO). In the presence of 100 hemolytic units/ml SLO, cAMP
      increased amylase release in a time- and dose-dependent manner. PKI-(5-24)
      peptide, a specific PKA inhibitor, markedly inhibited amylase release, but the
      extent of inhibition was approximately 50%. On the other hand, the PKA catalytic
      subunit highly purified from bovine hearts significantly induced amylase release.
      The release was strictly dependent on the presence of SLO and the catalytic
      activity of PKA added. The catalytic subunit dose dependently induced amylase
      release, but the heat-inactivated subunit had no stimulatory effect. PKI-(5-24)
      peptide completely blocked amylase release evoked by the subunit. These results
      clearly demonstrate that the catalytic subunit of PKA regulates cAMP-mediated
      amylase release through phosphorylation of unidentified protein(s) directly or
      indirectly involved in the process of exocytosis.

PMID- 7520912
TI  - The native v-Raf.hsp90.p50 heterocomplex contains a novel immunophilin of the
      FK506 binding class.
AB  - We have recently reported that v-Raf forms a native heterocomplex with rat heat
      shock protein (hsp) 90 and a 50-kDa phosphoprotein (p50) in stably transfected
      3Y1 fibroblasts (Stancato, L. F., Chow, Y-H., Hutchison, K. A., Perdew, G. H.,
      Jove, R., and Pratt, W. B. (1993) J. Biol. Chem. 268, 21711-21716). Several
      members of the nuclear receptor family exist in heterocomplexes containing hsp90
      and various members of the immunophilin protein family, including hsp56, an
      immunophilin of the FK506 binding class (Pratt, W. B. (1993) J. Biol. Chem. 268,
      21455-21458). In this work, we have asked if Raf is also associated with an
      immunophilin. We have immunoadsorbed v-Raf from stably transfected rat 3Y1
      fibroblasts and show that the immunoadsorbed v-Raf.hsp90.p50 heterocomplex binds
      the immunosuppressant drug [3H]FK506. The binding is of high affinity (KD 82 nM)
      and specific in the sense that it is competed by nonradioactive FK506 and
      rapamycin but not by cyclosporin A. The [3H]FK506 binding activity is eliminated
      when the heterocomplex proteins are dissociated from v-Raf. Using the 22W mutant
      of c-Raf in which the NH2-terminal half has been deleted, we show that the
      catalytic domain of the kinase is sufficient for the immunophilin association. We
      have shown that hsp90 and p50 do not bind FK506, and the v-Raf heterocomplex does
      not contain any of the established FK506-binding proteins. Thus, we propose that
      Raf is associated with a novel immunophilin.

PMID- 7520913
TI  - Characterization of the distal alpha-fetoprotein enhancer, a strong, long
      distance, liver-specific activator.
AB  - High level expression of the alpha-fetoprotein (AFP) gene is controlled by three
      upstream enhancers which function even in hepatic cell lines that repress the AFP
      gene promoter. The most distal ("Complex 3," at -6 kilobases) is the strongest in
      HepG2 cells. We mapped the main activity of Complex 3 to a 170-base pair (BP)
      region from -6069 to -5900; progressive deletion of the 5'- and 3'-ends
      identified an 84-bp segment which accounted for 90% of enhancer activity.
      Expression studies, which combined the deleted Complex 3 with an AFP or tk
      promoter chloramphenicol acetyltransferase gene fusion, resolved five regions in
      the enhancer (Ia, Ib, II, III, and IV). Deletion of Regions Ia or II strongly
      reduced stimulation of the AFP promoter, while Regions Ia and Ib were essential
      for stimulation of the tk promoter. Footprinting indicated multiple binding sites
      in regions Ia, Ib, and II. Gel shift and oligonucleotide competition demonstrated
      that Regions Ia and II had high affinity HNF3- and C/EBP-binding sites,
      respectively, while additional unidentified factors bound throughout Regions I
      III. Complex 3 is a powerful liver-specific transcriptional regulator and an
      important model of long distance gene activation.

PMID- 7520914
TI  - CD14-mediated translocation of nuclear factor-kappa B induced by
      lipopolysaccharide does not require tyrosine kinase activity.
AB  - During the course of serious bacterial infections, lipopolysaccharide (LPS) is
      believed to interact with macrophage receptors, resulting in the generation of
      inflammatory mediators and systemic symptoms including hemodynamic instability
      and shock. CD14, a glycosylphosphatidylinositol-linked antigen, functions as an
      LPS signaling receptor. A critical issue concerns the mechanism by which CD14,
      which has no transmembrane domain, transduces its signal following LPS binding.
      Recently, investigators have hypothesized that CD14-mediated signaling is
      effected through a receptor-associated tyrosine kinase (TK), suggesting a
      multicomponent receptor model of LPS signaling. Wild-type Chinese hamster ovary
      (CHO)-K1 cells can be activated by endotoxin to release arachidonate following
      transfection with human CD14 (CHO/CD14). Nuclear translocation of cytosolic NF
      kappa B is correlated with a number of LPS-inducible responses. We sought to
      determine if this pathway were present in CHO/CD14 cells and to elucidate the
      relationship of NF-kappa B activation to the CD14 receptor system. LPS-stimulated
      translocation of NF-kappa B in CHO/CD14 cells resembled the same response in the
      murine macrophage-like cell line RAW 264.7. Protein synthesis inhibitors and
      corticosteroids, which suppress arachidonate release and the synthesis of
      proinflammatory cytokines, had no effect on translocation of NF-kappa B in
      CHO/CD14 or RAW 264.7 cells, demonstrating that NF-kappa B translocation is an
      early event. Although TK activity was consistently observed by immunoblotting
      extracts from activated RAW 264.7 cells, LPS-induced phosphotyrosine residues
      were not observed from similarly treated CHO/CD14 cells. Furthermore, the TK
      inhibitors herbimycin A and genistein failed to inhibit translocation of NF-kappa
      B in CHO/CD14 or RAW 264.7 cells, although both of these agents inhibited LPS
      induced TK activity in RAW 264.7 cells. These results imply that TK activity is
      not obligatory for CD14-mediated signal transduction to occur in response to LPS.

PMID- 7520915
TI  - Ligand binding domain of granulocyte colony-stimulating factor receptor.
AB  - The amino-terminal domain of the cytokine receptor homologous region (BN domain;
      roughly 100 amino acid residues) in the receptor for murine granulocyte colony
      stimulating factor (G-CSF) was secreted as a maltose-binding protein fusion into
      the Escherichia coli periplasm. The murine BN domain (mBN) was prepared from the
      fusion protein by restriction protease Factor Xa digestion and purified to
      homogeneity. The purified BN domain specifically and stoichiometrically bound G
      CSF, with an apparent dissociation constant (Kd) of 3-8 x 10(-8) M. The CD
      spectrum of the mBN domain was similar to that of the extracellular region of the
      human growth hormone (GH) receptor, which is composed of turns and beta-sheets
      held together by disulfide bonds. Tertiary folding and the beta-sheet of this
      small domain was confirmed by NMR spectroscopy. Disulfide bonds determined by
      peptide mapping were in the following locations: Cys107-Cys118, Cys153-Cys162,
      and Cys143-Cys194. Among them, the first and the second produce small loops
      (roughly 10 amino acid residues) as found in the human GH receptor. These results
      suggested that the mBN domain of the G-CSF receptor expressed by E. coli has a GH
      receptor-like structure. However, the third disulfide bond varied considerably
      between the G-CSF and GH receptors. Disruption of these disulfide bonds in the BN
      domain of the G-CSF receptor suggested that all of them are critical for
      maintaining a stably folded protein. Our results will facilitate understanding of
      the biophysical and structural properties of this receptor.

PMID- 7520916
TI  - Use of TrpE fusion protein to identify antigenic domains within the BIV envelope
      protein.
AB  - Nine different recombinant clones spanning various regions of the bovine
      immunodeficiency-like virus (BIV) envelope gene open reading frame were
      generated. These clones span the entire external glycoprotein as well as the
      transmembrane glycoprotein region. These proteins were expressed as fusions to
      the TrpE protein in E. coli. The levels of recombinant protein expressed varied,
      some clones expressed enough protein that can be detected in a Coomassie blue
      stained gel, whereas other proteins could only be detected by Western blot
      analyses. A recombinant env protein representing the extracellular domain of the
      env protein was detected by BIV-infected bovine sera. In addition, a 134 amino
      acid peptide which may represent a major immunoreactive epitope was identified.
      This peptide is located at the amino terminus of the transmembrane glycoprotein
      and was specifically recognized by all BIV-infected calf sera tested. The
      identification of this epitope and the use of recombinant envelope protein will
      enable us to develop a more effective screening test to study the epidemiology of
      BIV infection.

PMID- 7520917
TI  - Regulation of experimental autoimmune encephalomyelitis: inhibition of adoptive
      experimental autoimmune encephalomyelitis by 'recovery-associated suppressor
      cells'.
AB  - We have previously shown the presence of suppressor cells in Lewis rats at the
      time of spontaneous recovery from experimental autoimmune encephalomyelitis
      (EAE). These cells, called 'recovery-associated suppressor cells' (RASC), are
      capable of preventing active EAE and inhibiting in vitro the specific
      proliferative response of encephalitogenic anti-MBP T cell line cells. The
      present investigations were undertaken in order to lend support to the hypothesis
      that RASC play an active role in the recovery. We found that RASC can prevent
      adoptive EAE when admixed with already activated, but not resting, anti-MBP T
      cells or when injected into the recipients separately from the encephalitogenic
      cells. They can also arrest the course of an ongoing disease when injected after
      the beginning of the clinical signs. This study provides the first direct
      demonstration of the downregulation of an ongoing EAE by suppressor cells.

PMID- 7520918
TI  - Myelin localization of a central nervous system ligand for L-selectin.
AB  - L-selectin is a lectin-like receptor involved in lymphocyte attachment to lymph
      node high endothelial venules (HEV). Previously, we showed that L-selectin also
      participates in the in vitro attachment of lymphocytes to central nervous system
      (CNS) white matter. Use of an L-selectin chimera demonstrated ligand sites within
      CNS white matter but not the peripheral nervous system (PNS). Now employing
      higher resolution mapping, including EM cytochemistry, we localize the ligands to
      the actual myelin sheaths of CNS neurons. In the shiverer mouse, which lacks
      compact myelin, ligands are greatly diminished. Comparison of the myelin
      associated ligand with the previously characterized HEV-ligands demonstrates a
      number of differences.

PMID- 7520919
TI  - Identification of a second T cell epitope of human proteolipid protein (residues
      89-106) recognized by proliferative and cytolytic CD4+ T cells from multiple
      sclerosis patients.
AB  - Research into the pathogenesis of multiple sclerosis (MS) has focused on myelin
      antigens as potential targets of autoimmune attack. Proteolipid protein (PLP) is
      the most abundant myelin protein comprising more than 50% of central nervous
      system myelin. Although PLP is a hydrophobic membrane protein which has made it
      difficult to study, the use of synthetic peptides based on the PLP sequence
      provides an alternative method for studying the immunological properties of PLP.
      Using peripheral blood lymphocytes from MS patients, long-term TCL established in
      the presence of PLP reacted weakly to PLP in proliferation assays; however, these
      same lines were much more reactive to synthetic peptides of PLP. Thus, we
      established short-term T cell lines (TCL) from the peripheral blood lymphocytes
      (PBL) of MS patients in the presence of five separate synthetic PLP peptides. In
      6/7 MS patients, proliferative responses were elicited most often to PLP 40-60
      compared to four other PLP peptides (PLP 89-106, 103-120, 125-143, and 139-154)
      (Pelfrey et al., 1993). Interestingly, however, the magnitude of the
      proliferative response was greatest in response to PLP 89-106. Characterization
      of PLP 89-106-responsive TCL from several MS patients, indicated that TCL
      proliferating to the peptide also lysed PLP 89-106 pulsed autologous targets. The
      majority of cytolytic PLP 89-106 TCL were CD4+ and MHC class II restricted and
      the predominant restriction elements were those most commonly found in MS
      patients. These findings suggest that the use of synthetic peptides represents a
      viable alternative approach to the study of PLP reactivity in humans. We report
      here that MS PBL recognize several PLP peptides, with the predominant responses
      to PLP 40-60 and PLP 89-106. Since these cells have both helper (CD4+) and
      cytolytic capabilities, it is possible that they may play a role in the
      pathogenesis or progression of MS.

PMID- 7520920
TI  - T lymphocyte subset abnormalities in peripheral blood from patients with the
      Guillain-Barre syndrome.
AB  - T lymphocytes are probably of pathogenic importance in many autoimmune diseases.
      Recently, deviations of circulating T-helper (CD4+) subpopulations have been
      noticed. Blood samples from 12 patients with Guillain-Barre syndrome (GBS) were
      studied with flow cytometry during their disease course to define circulating T
      cell populations. The proportion of T-helper cells (CD4+) was decreased (mean
      value 41 +/- 15%, P = 0.01) and the proportion of T cytotoxic/suppressor cells
      (CD8+) was increased (35 +/- 18%, P = 0.0006) as compared to the control group of
      healthy blood donors (47 +/- 8% and 26 +/- 7% respectively). The CD4+ population
      is divided into the helper/inducer (CD4+CD29+) and suppressor/inducer
      (CD4+CD45RA+) subsets, which normally are equally distributed (mean values in our
      control group were 45 +/- 15% and 44 +/- 15%, respectively). In patients with
      GBS, the helper/inducer (CD4+CD29+) subset was increased (54 +/- 10%, P = 0.05)
      and the suppressor/inducer (CD4+CD45RA+) subset was decreased (31 +/- 9, P =
      0.005) compared to the controls. The proportion of activated HLA-DR-expressing T
      cells was increased (7 +/- 8%, P = 0.005) as compared to controls (3 +/- 3%). The
      total proportions of T cells (CD2+), B cells (CD19+) and natural killer (NK)
      cells (CD56+) were similar in patients and controls. The CD4+ and CD8+
      populations, as well as the activated HLA-DR+ T cells, normalized during the
      disease course. The deviations within the CD4+ population also tended to
      normalize, but even at follow up after 6-33 (mean 23) months, some abnormalities
      remained. In conclusion, we confirm previous reports of T cell activation in
      peripheral blood from patients with GBS. A new finding is the deviation of T
      helper subpopulations with an increased helper/inducer (CD4+CD29+) subset and a
      decreased suppressor/inducer (CD4+CD45RA+) subset, which indicates a possible
      autoimmune character of GBS.

PMID- 7520921
TI  - Behavioral and physiological resistance to insecticides in the German cockroach
      (Dictyoptera: Blattellidae): an experimental reevaluation.
AB  - Although physiological resistance to pesticides has been demonstrated in German
      cockroaches, Blattella germanica (L.), behavioral resistance has not been shown
      clearly. To test for the possible development of behavioral resistance, choice
      test experiments were done to determine whether adult males and females from
      physiologically resistant and susceptible strains differed in avoidance of three
      emulsifiable formulations (chlorpyrifos, cypermethrin, and chlordane).
      Physiological resistance was verified by estimation of LC50s. Within 6 h, each
      cockroach chose between an untreated and a treated harborage. In the resistant
      strain, both sexes avoided harborages treated with cypermethrin and survived the
      choice tests, but more females than males avoided harborages treated with
      chlorpyrifos and survived. In the susceptible strain, neither sex avoided
      harborages treated with cypermethrin or chlorpyrifos, and most died. The
      physiologically resistant strain was more resistant to chlorpyrifos and
      cypermethrin than was the susceptible strain, with females generally having
      higher LC50s. However, in choice tests with chlordane in which physiological
      resistance levels were similar between the strains, the strains did not differ in
      avoidance of treated harborages or survivorship. Avoidance of treated harborages
      may be facilitated by high levels of physiological resistance, but we detected no
      behavioral resistance traits. High levels of physiological resistance permitted
      cockroaches to absorb an amount of pesticide that led to detection and subsequent
      avoidance of treated harborages. Results of our study suggest that previous
      research on insects has not demonstrated the evolution of stimulus-dependent
      behavioral resistance in field populations exposed to pesticides.

PMID- 7520922
TI  - Characterization of the 5' noncoding and structural region of the hepatitis C
      virus genome from patients with non-A, non-B hepatitis responding differently to
      interferon treatment.
AB  - We examined 14 patients with hepatitis C caused by infection with the hepatitis C
      virus-II genotype to understand differences in responsiveness to interferon. The
      patients were classified into two groups according to their response to
      interferon: eight responding and six non-responding patients. The 5' noncoding
      and structural regions of the hepatitis C virus-II genome from each patient
      specimen were amplified by reverse transcription followed by the polymerase chain
      reaction. The nucleotide sequences of these amplified DNAs were then determined.
      By comparing the nucleotide sequences and the deduced amino acid sequences of
      samples from both groups, no group-specific sequence was observed in the analyzed
      regions despite the presence of considerable sequence diversity. However,
      additional cysteine residues were observed in half the responding group. The
      degree of micro-heterogeneity in hypervariable region 1 of the hepatitis C virus
      in relation to the sensitivity to interferon treatment was also examined;
      however, no significant correlation was observed. In addition, frequent
      alterations in the amino acid sequences were observed in hypervariable region 1
      during the course of interferon treatment.

PMID- 7520923
TI  - Hepatitis C virus viremia following clinical resolution of acute hepatitis C.
AB  - Clinical resolution of acute hepatitis C occurs in a limited proportion of cases.
      However, the rate of hepatitis C virus persistence remains unclear. For this
      purpose, we conducted a serial study of 60 patients with hepatitis C virus
      infection from the early stage of the disease for 24 to 80 months (average 50
      months). Fourteen cases who recovered from acute hepatitis were selected from
      this group for prospective analysis of the behavior of liver enzymes, anti-HCV
      antibodies (RIBA II, Ortho Diagnostic System) and hepatitis C virus-RNA in serum
      and in peripheral blood lympho-mononuclear cells by nested polymerase chain
      reaction. Primers were derived from the 5'-untranslated region of the hepatitis C
      virus genome and the amplified products were detected by gel electrophoresis and
      a DNA enzyme immunoassay. All patients except two showed early recovery from
      acute hepatitis that occurred within 3 months from clinical onset. Transaminase
      normalization was always preceded by clearance of serum hepatitis C virus-RNA,
      which remained negative throughout follow-up. During the resolution phase of the
      disease a progressive decline in the antibody response was observed in most of
      the patients. At the end of the study anti-C100 was negative in half the cases,
      while anti-C33 and anti-C22 became negative or borderline in five cases.
      Hepatitis C virus-RNA was found in the peripheral blood lympho-mononuclear cells,
      but not in the serum, of only one of eight patients tested.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7520924
TI  - Organ distribution of a conjugate of adenine arabinoside monophosphate with
      lactosaminated albumin in the rat.

PMID- 7520925
TI  - Needle aspiration cytology in the diagnosis of mucinous cystadenocarcinoma of
      pancreas. A study of five cases with an emphasis on utility and differential
      diagnosis.
AB  - In this study, our experience with five cases of mucinous cystadenocarcinoma of
      the pancreas is described, which was seen over a 13-yr period. The diagnosis in
      four of the cases was made from aspirated material that was obtained under
      computed tomography (CT) guidance and, in one case, following an intraoperative
      aspirate. In four cases, the tumor was found to be in the head of pancreas,
      whereas in one case, the neoplasm was located in the tail. All the cases were
      elderly male patients. As a result of our study, it is believed that aspiration
      cytodiagnosis of mucinous cystadenocarcinoma (a rare subtype of pancreatic
      carcinoma) can be made with confidence when performed intraoperatively or with
      imaging assistance. Also, aspiration cytology is a sensitive, specific, and
      relatively simple procedure that provides adequate material on which a confident
      diagnostic interpretation can be made of this uncommon neoplasm.

PMID- 7520926
TI  - A rat model to study hypercalcemia-induced acute pancreatitis.
AB  - Hypercalcemia causes acute pancreatitis in humans, a phenomenon reproduced
      experimentally in cats and guinea pigs. Because the rat is the most frequently
      used animal for the study of experimental pancreatitis, the present studies were
      performed to evaluate the effects of hypercalcemia in the rat. In in vitro
      studies, pancreatic lobules were prepared from fasted Wistar rats (200-250 g) and
      incubated in HEPES bicarbonate-buffered medium (pH 7.4) containing 0, 0.6, 1.2,
      2.5, 5, and 10 mM CaCl2 with or without carbachol 10(-6) M. Amylase was measured
      in the medium after 30 min to 3 h, and expressed as percent of total amylase. In
      in vivo studies, fasted male Wistar rats (300-400 g) received calcium (CaCl2; 0.6
      mmol/kgh) into the tail vein for 12 h. Control animals received NaCl 0.9%
      infusion. Histologic slides (H&E-stained) were evaluated in a blinded fashion.
      Pancreatic lobules showed a higher basal amylase output when incubated in higher
      calcium medium. The largest, significant difference (2.6-fold) was between 0.6
      and 5 mM medium CaCl2 (p < 0.05). Carbachol-stimulated amylase release was again
      higher with increasing medium calcium with the most pronounced difference (1.3
      fold) between 0.6 and 2.5 mM CaCl2 (p < 0.05). In vivo calcium-treated animals
      showed accumulation of zymogen granules in the cytoplasm, cytoplasmic
      vacuolization, focal acinar cell depolarization, acinar necrosis, and edema.
      Calcium causes amylase release from rat pancreatic lobules in vitro. Higher
      medium calcium levels both significantly increase amylase release from
      unstimulated and carbachol stimulated lobules. Twelve-hour in vivo calcium
      infusion leads to accumulation of zymogen granules in acinar cells and acinar
      injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520927
TI  - Functional characterization of peripheral circulating and liver recruited
      neutrophils in endotoxic rats.
AB  - Neutrophil accumulation in tissue is a hallmark of inflammation and is associated
      with a variety of pathological conditions. In bacterial infection neutrophils are
      selectively attracted in large numbers to phagocytose and kill invading
      microorganisms. However, activated neutrophils can also cause injury to tissues.
      To investigate functional alterations in liver recruited neutrophils (PMNs), we
      studied the functional characteristics of circulating blood and liver sequestered
      PMNs in terms of host defense mechanisms, such as nitric oxide (NO) and
      superoxide (SO) generation, beta 2 integrin expression, phagocytosis, and
      eicosanoid profile. Cells were isolated from rats infused with a nonlethal dose
      (320 micrograms/kg) of E. coli endotoxin (ET) or pyrogen-free saline for 90 min.
      Liver PMNs produced significantly more NO both in the absence and in the presence
      of an in vitro endotoxin challenge than did blood PMNs. No significant difference
      was observed in phorbol myristate acetate-stimulated SO generation. Endotoxin
      infusion significantly up-regulated the expression of CD11b/c in circulating and
      even more so in liver PMNs. Phagocytosis was significantly enhanced by in vivo ET
      treatment in blood PMNs, and liver PMNs showed even greater phagocytic activity
      than blood PMNs or Kupffer cells. The percent distribution of prostaglandins D2
      and E2 of total 14C-eicosanoids was significantly higher and that of thromboxane
      B2 and 5-, 12-, and 15-HETEs was significantly lower in liver than in blood PMNs.
      Our study demonstrates several functional differences between liver-recruited and
      circulating PMNs in an acute endotoxic model. The implications of altered
      neutrophil function may extend to mechanisms of host defense and hepatotoxicity
      associated with sepsis and endotoxemia.

PMID- 7520928
TI  - Evidence for the expression of three different BoLA-class II molecules on the
      bovine BL-3 cell line: determination of a non-DR non-DQ gene product.
AB  - Studies were conducted to determine the reactivity of six monoclonal antibodies
      specific for major histocompatibility complex class II molecules expressed on a
      bovine B cell line homozygous for BoLA-DR and BoLA-DQ alleles. Direct
      immunoprecipitation, serial immunodepletion experiments, and two-dimensional gel
      electrophoresis revealed that these antibodies reacted with three different
      molecules. Bovine orthologues of HLA-DR were recognized by three monoclonal
      antibodies--H34A, TH12A, and TH14B. Orthologues of HLA-DQ were characterized by
      two other monoclonal antibodies, TH22A and TH81A. A third BoLA class II antigen,
      neither DR nor DQ was revealed by the last monoclonal antibody H42A. The relation
      of this molecule to known molecules in humans and other species remains to be
      established. However, cumulative data suggest that the determinant is expressed
      on a molecule related to HLA-DP.

PMID- 7520929
TI  - Growth hormone (GH) regulation of circulating insulin-like growth factor-I levels
      during sexual maturation of the GH-deficient dwarf (dw/dw) male rat.
AB  - In many mammalian species, circulating levels of insulin-like growth factor-I
      (IGF-I) rise during puberty. Previous studies manipulating testosterone levels in
      rats with normal GH secretion suggested that the pubertal IGF-I rise is regulated
      by an interaction between GH and sex steroids. Therefore, in a reciprocal study,
      IGF-I levels were examined during sexual maturation of the GH-deficient dwarf
      (dw/dw) rat which has a selective genetic deficiency of GH but normal sex steroid
      levels. Male dw/dw rats were treated with daily injections of recombinant human
      GH (200 micrograms/100 g body weight) or saline vehicle, from 28 to 70 days of
      age. Sexual maturation was determined to occur primarily between 42 and 63 days
      of age based on testis and seminal vesicle growth and plasma testosterone levels.
      GH treatment had no effect on seminal vesicle weights, plasma testosterone or
      gonadotrophins. GH administration resulted in a 7% increase in absolute testes
      weight (P < 0.05), but a 50% increase in body weight (P < 0.0001). These results
      supported previous findings that the reproductive development of dw/dw rats is
      essentially normal. Untreated dw/dw rats had no rise in IGF-I levels during
      sexual maturation. In contrast, treatment with GH produced a marked sustained
      rise in IGF-I levels (P < 0.0001). LIgand blots demonstrated GH induction of IGF
      binding protein-3 (IGFBP-3) and an IGFBP cluster at 32 kDa. The initially high
      immunoreactive IGFBP-1 levels (> 600 ng/ml) decreased by 49 days of age after
      which untreated dw/dw rats had significantly higher IGFBP-1 levels than GH
      treated dw/dw rats (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520930
TI  - Rapid changes in plasma concentrations of insulin-like growth factor-I (IGF-I),
      IGF-II and IGF-binding proteins during anaesthesia in young sheep.
AB  - Halothane anaesthesia in young sheep results in greatly increased plasma binding
      capacity for radiolabelled insulin-like growth factor (IGF), as demonstrated
      using size-exclusion chromatography. Most of the increased binding was at an
      estimated molecular mass range of 30-50 kDa, with a smaller increase evident at
      130-150 kDa. These changes were not evident in control animals which had food
      withheld for the same period. The progressive increase in plasma radioligand
      binding during anaesthesia was the net result of a rise in circulating levels of
      a 29-31 kDa IGF-binding protein (IGFBP), as shown by ligand blotting, and
      declining plasma concentrations of IGF-I and IGF-II. Recovery from anaesthesia
      was accompanied by the restoration of plasma IGFs and the IGFBP towards pre
      anaesthesia concentrations. The induced IGFBP was provisionally identified as
      IGFBP-1 because it bound anti-IGFBP-1 antiserum but not antibodies against IGFBP
      2, IGFBP-3 or IGFBP-4. The elevation of plasma IGFBP-1 immunoreactivity was
      associated with reduced concentrations of glucose and insulin, the regulators of
      IGFBP-1 in humans and rats. These results suggest that IGF experiments that
      require anaesthesia but assume that the anaesthetised state is representative of
      conscious sheep should be reassessed. A similar situation may occur with other
      mammalian species.

PMID- 7520931
TI  - Transfer of insulin-like growth factor (IGF)-I from blood to intestine:
      comparison with IGFs that bind poorly to IGF-binding proteins.
AB  - The net transfer of 125I-labelled insulin-like growth factor (IGF)-I from the
      blood to the distal small intestine was measured in anaesthetized lambs using a
      non-recirculating vascular-perfused intestine. To determine whether IGF-binding
      proteins (IGFBPs) reduce net IGF transfer, radiolabelled IGF-I was compared with
      two analogues, des(1-3)IGF-I and LR3IGF-I, which show reduced affinity for
      IGFBPs. Radiolabelled IGF-I, des(1-3)IGF-I or LR3IGF-I (1 ng/ml plasma) was
      infused for 45 min into the arterial supply of a 10 cm intestinal segment, either
      in the absence of added unlabelled peptide (high specific activity) or in the
      presence of a 100-fold excess of unlabelled homologous peptide (low specific
      activity) to achieve different proportions of free and complexed peptide. Very
      little degradation of radiolabelled peptides was detected in plasma, with 3-10%
      degradation in the intestinal tissue. Less than 5% of radiolabelled IGF-I
      remained as free peptide in the efferent venous plasma of the perfused segment at
      both specific activities. Bound radiolabelled IGF-I was found by size-exclusion
      chromatography mainly in the 30-50 kDa region, with a smaller proportion in the
      150 kDa peak. The net intestinal transfer of IGF-I, calculated as the sum of the
      proportions of infused tracer recovered from intestinal tissue, luminal contents
      and lymph, was 3.46 +/- 0.22% (S.E.M.) and 3.49 +/- 0.93% when infused at high
      and low specific activities respectively. The analogues differed from IGF-I with
      up to ninefold higher concentrations of free radiolabelled peptide in venous
      plasma of the perfused intestinal segment, and corresponding decreases in binding
      to the 30-50 kDa binding proteins. Notwithstanding these marked differences in
      the plasma levels of free peptide, net intestinal transfer was very similar for
      the three peptides, as was the extent of degradation in the intestinal tissue.
      The lack of correlation between binding to 30-50 kDa binding proteins and net
      intestinal transfer suggests that association with 30-50 kDa plasma binding
      proteins is not a rate-limiting determinant of net IGF transfer to intestinal
      tissue.

PMID- 7520932
TI  - Insulin-like growth factor-binding protein-3 expression and secretion by cultures
      of human prostate epithelial cells and stromal fibroblasts.
AB  - Prostate-specific antigen (PSA) was recently shown to be an insulin-like growth
      factor-binding protein (IGFBP)-3 protease. However, only IGFBPs-2 and -4 have
      been identified in conditioned medium of prostate epithelial cells. Using
      cultures of human prostate epithelial and stromal fibroblastic cells, we examined
      conditioned medium and cell extracts for evidence of IGFBP-3 expression and
      secretion. Western ligand blotting of conditioned medium from epithelial or
      stromal cultures revealed the presence of IGFBPs in the molecular weight range 36
      48 kDa, suggestive of IGFBP-3. Western immunoblots of these media confirmed the
      presence of IGFBP-3. Northern analyses of extracts of both stromal and epithelial
      cells showed a 2.5 kb band, the size of IGFBP-3 mRNA. We conclude that prostate
      cells express IGFBP-3 and that local proteolysis by PSA could modify this binding
      protein's actions in the prostate.

PMID- 7520933
TI  - Spatiotemporal pattern of expression of tenascin-like molecules in a developing
      insect olfactory system.
AB  - During the development of the olfactory (antennal) lobe of the moth Manduca
      sexta, olfactory sensory axons induce glomerular branching patterns in their
      target neurons. Glial cells, by surrounding the developing glomerular template,
      are thought to mediate the developmental influence of olfactory axons on these
      branching patterns. Previous studies have demonstrated that, in the absence of
      glia, neurons in the antennal lobe branch in an aglomerular fashion, even in the
      presence of competent antennal axons (Oland and Tolbert, 1988, J. Comp. Neurol.
      278:377-387; Oland et al., 1988, J. Neurosci. 8:353-367). We have begun to
      explore the molecular basis by which glial cells could influence patterns of
      neurite branching. For this work, we have utilized immunocytochemical techniques
      and a partial biochemical analysis to demonstrate that molecules antigenically
      similar and comparable in size to mammalian tenascin are localized on the
      neuropil-associated glial cells that form borders around glomeruli in the
      developing antennal lobe. These tenascin-like molecules associated with
      neuropilar glia are present at critical stages of glomerulus development;
      tenascin-like immunoreactivity declines after glomeruli form and become
      stabilized. Neither the arrival nor the absence of antennal axons in the lobe
      induces changes in either the molecular forms or the amounts of tenascin-like
      molecules. The spatiotemporal pattern of expression of tenascin-like molecules
      suggests that they are in a position to participate in the formation of a
      glomerular neuropil and could form a molecular barrier that constrains neurite
      outgrowth strictly to glomeruli.

PMID- 7520934
TI  - Sustained remission of immune-mediated red cell aplasia in a child after
      intravenous administration of gamma globulin.
AB  - A 4-year-old white boy with immune-mediated red cell aplasia and severe anemia
      was given high intravenous doses of gamma-globulin. The therapy was well
      tolerated and followed by complete resolution of the inhibition of erythropoiesis
      with no recurrence of disease. Eight months after discontinuation of treatment,
      the patient has a normal complete blood cell count.

PMID- 7520935
TI  - Pharmacologic treatment of thalassemia intermedia with hydroxyurea.
AB  - Three adult patients with beta-thalassemia intermedia were treated with
      hydroxyurea. Each had a significant but transient rise in total hemoglobin level
      associated with a variable increase in hemoglobin F.

PMID- 7520936
TI  - Pancreatitis associated with olsalazine and sulfasalazine in children with
      ulcerative colitis.

PMID- 7520937
TI  - Otitis media in early childhood and patterns of intellectual development and
      later academic performance.
AB  - Examined long-term associations between otitis media with effusion (OME) during
      the first 5 years of life and patterns of intellectual development from 3-8 years
      and academic performance after 3 years in elementary school. Fifty-five
      socioeconomically disadvantaged children were studied prospectively between birth
      and 8 years. OME history was routinely documented from birth through 5 years
      during well and illness periods. Two aspects of children's OME experience were
      examined in relation to developmental outcomes: timing (whether the OME occurred
      during infancy vs. preschool years) and nature (whether the OME tended to be
      recurrent or persistent). Although OME during the first 5 years of life was not
      related to patterns of overall intellectual development between ages 3 and 8
      years, recurrent OME during infancy was a negative predictor of teachers' ratings
      of children's task orientation/distractibility in the classroom. Results are
      interpreted in the context of the growing OME literature.

PMID- 7520938
TI  - Potent inhibitors of histamine release: polyhydroxylated sterols from the
      Okinawan soft coral Sinularia abrupta.
AB  - A new polyhydroxylated steroid (24-methylene-1 alpha, 3 beta, 11 alpha
      trihydroxycholest-5-ene-18-oic acid-3-acetate, 1) and known related compounds (2
      4) from the soft coral Sinularia abrupta have potently inhibited histamine
      release from rat peritoneal mast cells induced by anti-immunoglobulin E. The
      inhibitory effect of 1 was approximately 6500 times stronger than that of
      disodium cromoglycate, a well-known antiallergic drug.

PMID- 7520939
TI  - The effect of recombinant cytokines on [14C]-aminopyrine accumulation by isolated
      canine parietal cells.
AB  - Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been shown
      to inhibit basal and pentagastrin-stimulated gastric secretion in rats and
      histamine-stimulated secretion in dogs. IL-1 also reduces the severity of ethanol
      and stress-induced gastroduodenal damage. The aim of this study was to examine
      the effects of human recombinant IL-1 alpha and TNF-alpha on enzymatically
      dispersed and enriched (> 90%) parietal cells stimulated with histamine,
      histamine plus 3-isobutyl-1-methylxanthine (IMX) or carbachol (all 10(-5) M).
      Acid secretion was assessed indirectly by quantitating [14C]-aminopyrine (AP)
      accumulation. IL-1 alpha (500 and 1000 ng/ml) inhibited histamine-stimulated AP
      uptake by 53% and 60% respectively, and it inhibited IL-1 alpha (1500 ng/ml) by
      69%. IL-1 alpha (500 and 1000 ng/ml) inhibited histamine plus IMX-stimulated AP
      uptake by 36% and 34%, respectively. IL-1 alpha (500 ng/ml) also inhibited
      carbachol-stimulated AP accumulation. TNF-alpha (100 and 250 ng/ml) inhibited
      histamine-stimulated AP accumulation by 38% and 36%, respectively. TNF-alpha also
      significantly inhibited histamine/IMX- and carbachol-stimulated AP uptake (P < or
      = .01). Indomethacin did not affect IL-1 alpha-induced inhibition. These results
      show that IL-1 alpha and TNF-alpha inhibit histamine- and carbachol-stimulated
      isolated parietal cell secretion and that, for IL-1 alpha, this effect does not
      depend on mucosal prostaglandin synthesis.

PMID- 7520940
TI  - Effects of E-4031, almokalant and tedisamil on postrest action potential duration
      of human papillary muscles.
AB  - The new antiarrhythmic compounds E-4031 (1-[2-(6-methyl-2-pyridyl)ethyl]-4-(4
      methylsulfonyl- aminobenzoyl)piperidine), almokalant and tedisamil prolonged the
      action potential duration (APD) of human right ventricular papillary muscle. In
      order to investigate whether drug-channel interaction takes place during rest,
      regular stimulation (0.5 Hz) was interrupted by three 30-min periods of
      quiescence. Drug was added at the beginning of the second period of rest, the
      third period was interposed at equilibrium of drug action. Under predrug control
      conditions, the first action potential after rest was longer than with regular
      stimulation, steady state was reached again with a monotonic time course. With E
      4031 the first action potential after 30 min of drug exposure during quiescence
      was similar to predrug control, but drug-induced prolongation of APD developed
      during further stimulation, indicating drug interaction with open channels. After
      the third period of quiescence, the first APD remained significantly increased
      compared to predrug values suggesting that E-4031 may be trapped within the
      resting channel. With almokalant, however, the first APD after wash-in was
      already prolonged and APD increased further with regular pacing. The effect was
      partially reversed during the third period of rest. These findings are compatible
      with open-channel block or no evidence for trapping. On the other hand, tedisamil
      prolonged APD but did not change the monophasic time course neither when added
      during quiescence nor at equilibrium of drug action. It is concluded that changes
      in APD after quiescence indicate differences among these drugs in their
      interactions with channel subtypes controlling repolarization.

PMID- 7520941
TI  - A further analysis of the contraction induced by activation of cholecystokinin A
      receptors in guinea pig isolated ileum longitudinal muscle-myenteric plexus.
AB  - The activity of a selective cholecystokinin (CCK)-A receptor agonist, N-acetyl
      derivative of A71623 (Ac-Trp-Lys(epsilon-N-[2-methylphenylamino-carbonyl]) -Asp
      (NMe)Phe-NH2) was investigated in the guinea pig isolated ileum longitudinal
      muscle myenteric plexus. NAA caused both a phasic and tonic contraction at all
      concentrations tested (1-1000 nM). The selective CCK-A antagonist L-364,718
      (Devazepide) antagonized both types of contraction with a pKB of 10.10 and 9.95,
      respectively. The CCK-B selective antagonist L-365,260 ((3R(+)-2,3-dihydro-1
      methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3yl)-N-(3-methylphenyl)-urea) was
      inactive up to a concentration of 30 nM. Atropine at 300 nM and 1000 nM reduced
      the maximal response of NAA by only 17% and 50%, respectively. The selective
      neurokinin (NK)-1 antagonists GR 82334 ([D-pro9[Spiro-gamma-Lactam] Leu10, Trp11]
      Phys (1-11)9) at 300 and 1000 nM and (+-) CP-96,345 [(2S, 3S)-cis- 2
      (diphenylmethyl)-N- [(2-methoxyphenyl)-methyl] -1-azabici-clo [2.2.2]octan-3
      amine] at 10 nM were inactive or partially active. When atropine and GR 82334 or
      (+/-) CP-96,345 were combined, they produced a dose-dependent synergistic
      inhibition of both phasic and tonic contractions induced by NAA. The selective NK
      3 receptor agonist senktide induced both phasic and tonic contractions that were
      blocked by tetrodotoxin. In the presence of atropine and GR 82334, both 300 nM, a
      synergistic depression of the response to senktide similar to that observed for
      the agonist NAA was disclosed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520942
TI  - Signal transducing mechanisms coupled to histamine H3 receptors and alpha-2
      adrenoceptors in the guinea pig duodenum: possible involvement of N-type Ca++
      channels.
AB  - The signaling pathways following histamine H3 receptor activation by (R)alpha
      methylhistamine (MHA) have been examined in the isolated guinea pig duodenum, in
      which selective excitation of cholinergic neurons was induced by electrical field
      stimulation (EFS). The effect of MHA on electrically evoked contractions was
      compared with that induced by the alpha-2 adrenoceptor agonist clonidine (CLON).
      The inhibitory effect of MHA on EFS-induced contractions was significantly
      reduced by increasing CA++ content in the nutrient fluid from 2.5 to 5 mM and by
      the Ca++ agonist Bay K 8644 (10(-8) M); conversely, the effect of MHA was
      significantly enhanced by lowering Ca++ content in the medium (from 2.5 to 1.25
      mM) and by the N-type Ca++ channel blocker omega-conotoxin (CTX) (10(-8) M). The
      L-type Ca++ channel blocker nifedipine (NIF) (10(-7) M) did not modify the effect
      of MHA, although it significantly reduced both EFS- and exogenous acetylcholine
      (ACH)-induced contractions. Similar to MHA, the inhibitory effect elicited by
      CLON was enhanced by low external Ca++ and by CTX, but it was slightly affected
      by the compound Bay K 8644 (10(-7) M) or by high Ca++ concentrations (5 mM) and
      it was unaffected by NIF. 4-Aminopyridine (4-AP) (10(-4) M) reduced the effects
      of both MHA and CLON. The present data indicate that histamine H3 receptor
      activation in electrically stimulated duodenum is closely associated with a
      restriction of Ca++ access into the nerve terminal through N-type Ca++ channels;
      the same mechanism appears to be responsible for the inhibitory effect induced by
      alpha-2 adrenoceptor activation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520943
TI  - Aza-tricyclic substance P antagonists.
AB  - The synthesis and structure-activity relationships of a series of aza-tricyclic
      analogs of the quinuclidine substance P (SP) antagonist 1 are described. The SP
      receptor affinity of these compounds was found to vary according to the size of
      the new ring fused to the quinuclidine and the mode of fusion. Correlations
      between receptor affinity and (1) the steric bulk of the newly introduced ring
      fusion and (2) the dihedral angle between the benzhydryl and benzylamino
      substituents of these aza-tricyclic compounds were explored.

PMID- 7520944
TI  - Dietary supplementation with taurine and niacin prevents the increase in lung
      collagen cross-links in the multidose bleomycin hamster model of pulmonary
      fibrosis.
AB  - Taurine and niacin have been previously found to block the accumulation of
      collagen in lung in the multidose bleomycin hamster model of pulmonary fibrosis.
      Previous studies have found an increase in the pulmonary collagen cross-links
      dihydroxylysinonoroleucine (DHLNL) and hydroxypyridinium (OHP) in the single dose
      bleomycin rat model. In this study, we asked if taurine and niacin would block
      the increase in DHLNL and OHP in the multidose bleomycin hamster model of lung
      fibrosis. Hamsters were intratracheally instilled with three consecutive doses of
      saline or bleomycin sulfate 1 week apart (2.5, 2.0, 1.5 units/5 mL/kg). Animals
      were fed diet containing either 2.5% niacin and 2.5% taurine or control diet
      throughout the experiment. The four groups were saline-instilled with control
      diet (SCD), bleomycin instilled with control diet (BCD), bleomycin-instilled with
      taurine-niacin in diet (BTN), and saline-instilled with taurine-niacin in diet
      (STN). Animals were sacrificed at 1, 4, and 8 weeks after the last bleomycin
      instillation. Hydroxyproline per lung in the BCD group was significantly elevated
      by 38, 56, and 60% over the SCD group at 1, 4, and 8 weeks, respectively. There
      were no statistically significant differences among the four groups in DHLNL
      (mmole) per mole collagen at the 1 or 8 week time point. At four weeks, DHLNL was
      significantly elevated by 46.4% in the BCD group over the SCD group. The OHP
      (mmole) per mole of collagen at 1 and 4 weeks in the BCD group was not
      statistically different from the SCD group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520945
TI  - Costello syndrome: natural history and differential diagnosis of cutis laxa.
AB  - Costello syndrome is emerging as a better delineated condition and should be
      included in the differential diagnosis of cutis laxa in association with
      postnatal growth retardation and developmental delay. We present a further case
      of Costello syndrome which illustrates the natural history of this condition.

PMID- 7520946
TI  - HIV-1 reverse transcription. A termination step at the center of the genome.
AB  - During HIV-1 reverse transcription, the plus-strand of viral DNA is synthesized
      as two discrete segments. We show here that synthesis of the upstream segment
      terminates at the center of the genome after an 88 or 98 nucleotide strand
      displacement of the downstream segment, initiated at the central polypurine
      tract. Thus, the final structure of unintegrated linear HIV-1 DNA includes a
      central plus-strand overlap. In vitro reconstitution using only purified reverse
      transcriptase with appropriate DNA hybrids gave rise to efficient and accurate
      termination, which was dramatically amplified in the context of strand
      displacement. Mutation of the sequence immediately upstream of the termination
      sites almost completely abolished termination both in infected cells and in
      vitro. This mutation profoundly impaired replication of HIV-1. We conclude that
      proper central plus-strand termination, mediated by a novel cis-active
      termination sequence, is a key step in HIV-1 replication.

PMID- 7520947
TI  - Mechanism of FK506-induced glucose intolerance in rats.
AB  - To clarify the mechanism of glucose intolerance induced by FK506, a novel
      immunosuppressant, 5 or 10 mg/kg/day of FK506 was dosed orally to rats for 2
      weeks, and 125I-insulin binding to the erythrocytes, plasma glucose and insulin
      levels, and pancreatic insulin content were examined. Insulin binding to the
      erythrocytes of rat dosed with FK506 was similar to that to erythrocytes of the
      placebo control; Scatchard analysis confirmed that FK506 did not cause damage to
      the insulin receptor of the erythrocytes. Contrarily, FK506 caused a clear
      decrease of pancreatic insulin content as well as a slight decrease of plasma
      insulin level. The results suggest that the glucose intolerance induced by FK506
      is associated with a decrease of insulin secretion, but is not associated with
      impairment of the insulin receptor.

PMID- 7520948
TI  - Influence of preoperative positive seminal vesicle biopsy on the staging of
      prostatic cancer.
AB  - A total of 71 patients with clinically localized prostatic cancer underwent
      preoperative biopsy of each seminal vesicle. Group 1 (67 patients) underwent 2
      seminal vesicle biopsies before lymph node dissection and vesiculo-prostatectomy,
      while group 2 (4 patients) underwent seminal vesicle biopsy and lymph node
      dissection before radiation therapy. In group 1 there were 11 positive biopsies
      (16.5%) with a median prostate specific antigen (PSA) level of 24 ng./ml. (range
      11 to 45). Of the biopsies 56 were normal, with a median PSA level of 11.8 (range
      3.5 to 88, p < 0.008). Histological examination of the seminal vesicles on the
      prostatectomy specimen revealed 18 cases of seminal vesicle invasion (sensitivity
      61%, specificity 100%, positive predictive value 100% and negative predictive
      value 87.5%). A positive biopsy was correlated with the mean tumor volume (10.3
      cc with positive biopsies versus 4.9 cc with negative biopsies) and local
      invasion (positive margins in 36% versus 9%, respectively, and capsular
      perforation in 81% versus 25%, respectively). In group 2 the 4 seminal vesicle
      biopsies and lymph node dissections were positive. Overall (groups 1 and 2),
      positive seminal vesicle biopsies were predictive of lymph node involvement in
      47% of the cases versus 7% when biopsies were negative (p > 0.001). The
      postoperative course was significantly different (local recurrence and metastases
      in 45% versus 9%, respectively, and median interval 8.8 months versus 18.3
      months, respectively, p < 0.001). Seminal vesicle biopsy appears to have a
      satisfactory yield only in cases with a PSA level of greater than 10 ng./ml. A
      positive seminal vesicle biopsy confirms the presence of extraprostatic invasion
      of clinically localized cancer in a given patient. Seminal vesicle biopsy allows
      for better staging of prostatic cancer.

PMID- 7520949
TI  - Rate of change in serum prostate specific antigen levels as a method for prostate
      cancer detection.
AB  - To examine prospectively the usefulness of measurement of rate of change in serum
      prostate specific antigen levels (PSA slope) in detecting prostate cancer in a
      PSA-based prostate cancer screening study, we evaluated 982 serially screened men
      whose initial screening was negative for cancer. All men had at least 1 PSA value
      greater than 4.0 ng./ml. and all ultimately underwent prostatic biopsy. For those
      who entered the study with normal PSA levels, a PSA slope cutoff point of 0.75
      ng./ml. per year or more maximized sensitivity and specificity for predicting
      cancer (odds ratio 7.20, 95% confidence interval 4.52 to 11.47). This cutoff
      point was most predictive for men 70 years old or younger. For men who entered
      the study with elevated PSA levels (greater than 4.0 ng./ml.) a lower PSA slope
      cutoff point (0.4 ng./ml. per year or more) maximized sensitivity and specificity
      for predicting cancer (odds ratio 2.73, 95% confidence interval 1.82 to 4.07). We
      conclude that PSA slope is useful for serial prostate cancer screening, although
      its predictive value varies with patient age and initial PSA level.

PMID- 7520950
TI  - Prostate cancer diagnosis.

PMID- 7520951
TI  - Re: Laparoscopic pelvic lymph node dissection: a review of 103 consecutive cases.

PMID- 7520952
TI  - Colocalization of nitric oxide synthase with vasoactive intestinal peptide,
      neuropeptide Y, and tyrosine hydroxylase in nerves supplying the human ureter.
AB  - The distribution and patterns of colocalization of nitric oxide synthase (NOS),
      vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and the catecholamine
      synthesizing enzyme tyrosine hydroxylase (TH) were examined in nerve fibers
      supplying the human lower ureter using double label immunofluorescence. Many
      nerve fibers immunoreactive for NOS were observed within the ureter. Positive
      varicose fibers were seen running longitudinally within the smooth muscle
      bundles, particularly those of the inner layers of the ureter. Immunoreactive
      axons were also prominent within the subepithelium, and as plexi surrounding many
      blood vessels. The colocalization studies indicated that NOS was never present in
      presumptive sympathetic nerve fibers expressing TH. All fibers containing VIP,
      however, were also immunoreactive for NOS. In addition, a minor population of NOS
      fibers did not contain VIP. Neuropeptide Y coexisted with NOS in a significant
      number of nerve terminals, although fibers expressing only NPY were equally
      common. Several immunochemically distinct nerve populations can therefore be
      distinguished in the human ureter: (1) nerves containing NOS either with or
      without VIP; (2) NOS-immunoreactive fibers with NPY; and (3) those fibers
      expressing TH or NPY which do not contain NOS. The results indicate that some non
      noradrenergic peptide-containing nerves in the human ureter have the capacity to
      synthesize nitric oxide (NO), and that NO may be involved in the regulation of
      ureteric motility.

PMID- 7520953
TI  - [The usefulness of early whole body bone scintigraphy in the detection of bone
      metastasis from prostatic cancer].
AB  - Early whole body bone scintigraphy was performed on 25 patients with prostatic
      cancer (15 cases with bone metastases and 10 cases without bone metastasis) to
      obtain anterior and posterior whole body images five minutes after administration
      of 99mTc-HMDP. The results were compared with the findings of routine bone
      scintigraphy after three hours, and the usefulness of the above method for the
      diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in
      which increased activity was found in the upper and lower lumbar vertebrae by
      routine bone scintigraphy but no abnormality was seen by early whole body bone
      scintigraphy, senile degenerative bone changes such as spondylosis deformans were
      observed by bone radiography. In cases with multiple bone metastases, abnormal
      multiple accumulations were found by both early whole body bone scintigraphy and
      routine bone scintigraphy. In addition, in cases showing super bone scan, high
      accumulation in the skeletal system had already been detected by early whole body
      bone scintigraphy. When the courses before and after treatment in nine cases of
      multiple bone metastases were passaged from the results of early whole body bone
      scintigraphy and from changes in tumor markers (prostatic specific antigen, gamma
      semino protein and prostatic acid phosphatase), increased activity and the
      appearance of new hot spots as well as an increase in tumor markers were detected
      by early whole body scintigraphy in three of the four advanced cases, whereas
      decreased accumulations and a decrease in and normalization of tumor markers were
      observed in five improved cases.

PMID- 7520954
TI  - Albumin and transferrin synthesis are increased in H4 cells by serum from
      analbuminemic or nephrotic rats.
AB  - The hepatic synthesis of several proteins, including both albumin and transferrin
      is increased in the nephrotic syndrome. While active suppression of albumin
      synthesis by lymphokines has been described, it has been assumed that
      augmentation of albumin synthesis is governed by a physical factor, plasma
      oncotic pressure (pi), and that this regulation is by a direct effect of pi on
      hepatocytes. The mechanisms have not been defined. Furthermore, experiments
      relying on suppression of protein synthesis may only test non-specific inhibitory
      effects of the experimental intervention. We tested an alternative hypothesis
      that a serum factor(s) present in hypooncotic states stimulates albumin
      synthesis. We incubated an immortalized cell line derived from rat hepatocytes
      (H4 cells) with serum from Nagase analbuminemic rats (NAR) and rats with passive
      Heymann nephritis (HN), a model of the nephrotic syndrome. Synthesis
      (incorporation of [35S]methionine) into both albumin and transferrin was
      increased significantly. The stimulatory effect of these sera was not
      extinguished by addition of rat or human albumin to the medium prior to or during
      incubation, even when pi in the incubation medium was increased to normal plasma
      levels by added albumin. Incorporation of [35S]methionine into albumin was 7841
      +/- 394 cpm/mg cell protein using 10% NAR serum in the presence of human albumin
      (medium pi 26.1 +/- 0.17) versus 5149 +/- 420 cpm incorporation (P < 0.05) in the
      presence of control serum and in the absence of added albumin (medium pi 2.06 +/-
      0.26 mm Hg, P < 0.001). The stimulatory activity was preserved following heating
      of serum for one hour at 60 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520955
TI  - Functional characterization of cytokine autoantibodies in chronic renal failure
      patients.
AB  - We have recently reported on an increase of IL-1 alpha and IL-6 autoantibodies in
      patients maintained on chronic hemodialysis treatment. The aim of the present
      study was to evaluate functional properties of these autoantibodies. Serum
      samples of more then 500 chronic renal failure patients with and without
      replacement therapy were screened for the presence of IL-1 alpha and IL-6
      autoantibodies by second antibody precipitation. The neutralizing capacity of IL
      1 alpha autoantibody serum was studied by immunofluorescence flow cytometry
      analysis of IL-1 alpha induced expression of E-selectin (ELAM-1, CD62e) on HUVEC
      (human umbilical vein endothelial cells). Results of these inhibition studies
      were confirmed with IgG preparations from antibody positive sera, purified by
      affinity chromatography. Functional studies on IL-6-dependent B9 cell
      proliferation were performed with IL-6 autoantibody positive sera, and
      quantitated with the colorimetric MTT assay. IL-1 alpha induced expression of E
      selectin on HUVEC (considered 100% positive cells) was inhibited by each IL-1
      alpha autoantibody positive serum sample (N = 13; anti-IL-1 alpha activity: 7.62
      to 57.52% binding). Inhibition of E-selectin expression by IL-1 alpha
      autoantibodies ranged from 0.11 to 80.22% positive cells (0.15 to 92.31% mean
      fluorescence intensity). A strong correlation of E-selectin expression with IL-1
      alpha autoantibody concentration was observed (P < 0.005). Furthermore, IgG
      eluates from autoantibody positive patients inhibited E-selectin expression to
      41.0 +/- 23.1% positive cells if compared with 83.7 +/- 5.7% positive cells of
      the IgG depleted serum samples.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520956
TI  - The influence of early postoperative intraperitoneal chemotherapy on human wound
      healing.
AB  - Cell ingrowth, hydroxyproline accumulation, and mRNA expression of collagen I
      were measured in two polytetrafluoroethylene grafts implanted subcutaneously at
      the time of colorectal cancer surgery to evaluate the influence of early
      postoperative chemotherapy on human wound healing. Eleven patients treated with
      intraperitoneal 5-fluorouracil and intravenous folinic acid Days 1-6 after
      operation were compared with 15 patients who underwent surgery alone. At 1 week,
      chemotherapy-treated patients had accumulated less hydroxyproline (mean 0.35 +/-
      0.33 micrograms/cm) compared with untreated patients (mean 0.73 +/- 0.37
      micrograms/cm, P < 0.05). By 2 weeks, the hydroxyproline content had increased
      sixfold in the chemotherapy group (P < 0.01) and threefold in the nonchemotherapy
      group (P < 0.01) and there was no difference between the groups. Cell and
      connective tissue ingrowth and total RNA content did not differ between the
      groups at any point in time, but at 1 week the mRNA expression of collagen I was
      higher in the chemotherapy group (P < 0.05). These results indicate that collagen
      accumulation in human subjects is reduced during a short course of postoperative
      chemotherapy and normalizes after the end of treatment.

PMID- 7520957
TI  - Evolution of antigen drift/switching: continuously evading pathogens.
AB  - Following infection to a host, some pathogens repeatedly alter their antigen
      expression, and thereby escape the immune defense (antigen drift/switching). This
      paper examines the evolutionarily stable mutation rate of pathogens which
      maximizes the stationary pathogen density in a host. Assumptions are: (i) most
      mutations are deleterious but a minor fraction, p, of mutations can contribute to
      the alternation of antigenic property of the pathogen; and. (ii) potential
      antigen types can be indexed in a one-dimensional lattice (the stepping-stone
      model). The model reveals that: (a) if the mutation rate is higher than a
      threshold mu(c) = R0/(1-p), where R0 is the per capita growth rate of pathogen
      before the immune system is activated, pathogens cannot maintain themselves
      because too many progeny are lost by lethal mutations; (b) if the mutation rate
      lies between zero and mu(c), the system converges to a traveling wave of antigen
      variants with a constant wave speed; (c) the evolutionarily stable mutation rate
      microESS is unexpectedly high: more than 0.25 per genome per replication even if
      most mutations are lethal. Hence more than a fourth of progeny are born defective
      in the evolutionarily stable state; (d) the microESS is even higher if multiple
      infections by pathogens are common. The paper also studies the evolutionarily
      stable mutation rate if every mutant antigen belongs to a different type (the
      infinite allele model), and the evolution of antigen switching between a finite
      number of antigen variants stored in the pathogen genome.

PMID- 7520958
TI  - Ferroelectric active models of ion channels in biomembranes.
AB  - Ferroactive models of ion channels in the theory of biological membranes are
      presented. The main equations are derived and their possible solutions are shown.
      The estimates of some experimentally measured parameters are given. Possible
      physical consequences of the suggested models are listed and the possibility of
      their experimental finding is discussed. The functioning of the biomembrane's ion
      channel is qualitatively described on the basis of the suggested ferroactive
      models. The main directions and prospects for development of the ferroactive
      approach to the theory of biological membranes and their structures are
      indicated.

PMID- 7520959
TI  - The role of lysosomal alterations in the damage to the pancreas and liver in
      acute experimental pancreatitis in dogs.
AB  - The role of lysosomal hydrolases in the pathogenesis of acute pancreatitis and
      secondary liver injury, as an important aspect of multisystem organ failure,
      remains unclear. The purpose of this study was to assess the lysosomal fragility
      in both organs in acute experimental pancreatitis (AEP) of graded severity in
      dogs. In 7 dogs, the moderate (M) and in 13 dogs severe (S) variant of bile-
      trypsin AEP--was induced; 6 dogs were in control group (C). The 24 h survival
      time was 6/7 and 6/13, respectively. After that time, the dogs were sacrificed
      and the lysosomal enriched subfraction (L) from both organs was isolated by
      ultracentrifugation. The total (T) and free (F) activities of beta-glucuronidase
      (beta G), cathepsins (Cs) and acid phosphatase (AcP) according to Gianetto and de
      Duve were assayed. The fractional free activity (% F/T) was adapted as and index
      of lysosomal stability. The %F/T of BG in the homogenate of the pancreas in
      AEP(S) was higher than that in AEP(M) (92% vs. 71%, p < 0.05, and vs. 37% in C, p
      < 0.005). The %F/T of Cs and AcP showed a similar pattern. The %F/T of beta G in
      L of the liver in AEP(S) was 38% vs. 29% in AEP(M), (p < 0.05), and vs. 20% in C
      (p < 0.05). In AEP in dogs the %F/T activities of lysosomal hydrolases in the
      pancreas and liver were increased, suggesting the labilization of lysosomal
      membranes in severe form of this disease. Our results support the pathogenic role
      of lysosomal hydrolases in the damage to the pancreas and liver in acute
      pancreatitis.

PMID- 7520960
TI  - Clostridium difficile toxin A stimulates enzyme secretion from isolated rat
      pancreatic acini.
AB  - Although Cl difficile bacteremia and the presence of antibodies to toxin A (TxA)
      have been reported, little information is available at present on TxA effect on
      the functional properties of various visceral organs. We have, therefore,
      examined the in vitro effects of TxA on amylase and trypsin secretion from rat
      isolated pancreatic acini. Dispersed rat pancreatic acini were exposed for 60 min
      to different concentrations of highly purified TxA and the rate of amylase,
      trypsin and LDH release were monitored. Free cytosolic calcium release in
      pancreatic acini after toxin A (10(-10)M to 10(-8)M) treatment was measured with
      Fura-2/AM, Ca-indicator dye. TxA (10(-10) to 10(-8)M) increased significantly the
      rate of both the amylase and trypsin secretion without any membrane damage, with
      toxin A exerting its action via calcium dependent pathway as suggested by
      intracellular calcium release measured with Fura-2/AM.

PMID- 7520962
TI  - The hormonal profile in ectopic pregnancies.
AB  - The hormonal profile in a patient with an ectopic pregnancy (EP) differs in many
      respects from that of a patient with a normal intrauterine pregnancy (IUP).
      Although there are several reports using different hormones for early diagnosis
      of ectopic pregnancy most of the results are contradictory. In this study,
      therefore, we prospectively investigated the maternal serum level of beta-human
      chorionic gonadotropin (beta-hCG), progesterone (P), estradiol (E2), human
      placental lactogen (HPL), alfafetoprotein (AFP) and cancer antigen 125 (CA 125)
      during the first trimester of normal and abnormal pregnancies. Serum samples were
      obtained from 20 women with normal IUPs, 15 women whose pregnancies complicated
      with spontaneous abortion and 31 women with surgically and pathologically
      confirmed EPs. The mean serum levels of beta-hCG, E2 and p in patients with EPs
      (9490.55 +/- 3071.2 mlU/ml, 100.1 +/- 22.09 pg/ml, 4.18 +/- 1.19 ng/ml,
      respectively) were significantly lower than those measured in normal IUPs
      (73796.8 +/- 15554.7 mlU/ml, 500.15 +/- 98.84 pg/ml, 19.2 +/- 2.8 ng/ml,
      respectively p < 0.001) and significantly lower than in patients with spontaneous
      abortion (22524 +/- 6213 mlU/ml, p < 0.05, 339.8 +/- 112.16 pg/ml, p < 0.01,
      10.59 +/- 3.03 ng/ml, p < 0.05 respectively). No significant difference was
      recorded with respect to serum levels of HPL, AFP and CA 125 among the groups. We
      also investigated the diagnostic value of simple E2 and P in patients with EPs.
      We could not identify a discriminatory cutoff value because there was a
      considerable overlap in serum P and E2 levels between the patients with IUPs and
      EPs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7520961
TI  - Pre-stimulation of the human bone marrow CD34+ cells before storage at 4 degrees
      C with the early acting cytokines enhance their survival and increase
      proliferative potential. Transplantological implications.
AB  - The aim of this study was to evaluate whether short prestimulation of the human
      bone marrow CD34+ cells before storage at 4 degrees C with early acting cytokines
      would improve their subsequent survival and clonogenecity. To address this
      question the cells were placed in iscove medium supplemented with 20% BCS and
      stimulated for 24 hours in 37 degrees C incubator with different combination of
      the early acting cytokines (KL, IL-1 beta, IL-3, IL-6). Subsequently the cells
      were shifted to 4 degrees C. On day 6 the cells were plated in methylcelulose
      cultures and stimulated to growth CFU-GM colonies. It had been found that 24
      hours long pre-stimulation with early acting cytokines significantly enhances the
      survival of the CD34+ clonogeneic progenitors stored subsequently at 4 degrees C.
      The CD34+ cell prestimulated for 24 hours at 37 degrees C with KL + IL-3 and than
      shifted to 4 degrees C formed more than twice as much CFU-GM colonies in
      comparison to the cells stored whole time at 4 degrees C even in the presence of
      KL + IL-3. Therefore we suggest, that if there is a need to store bone marrow
      cells before transplantation for short time they should be prestimulated with
      early acting cytokines for 24 hours in liquid culture at 37 degrees C first and
      than placed at 4 degrees C. The data presented in this paper should be in the
      future confirmed in in vivo SCID animal model to evaluate the repopulation
      ability of marrow cells pre-stimulated before short term storage at 4 degrees C
      with early acting cytokines to enhance the proliferative potential of the
      transplant and to shorten the dangerous aplastic phase in the patients after
      transplantation.

PMID- 7520963
TI  - Towards a vaccine for rheumatic fever: identification of a conserved target
      epitope on M protein of group A streptococci.
AB  - Rheumatic fever and rheumatic heart disease remain very common in developing
      countries, and a vaccine to protect against these disorders would have a great
      impact on public health. A vaccine must target the M protein of group A
      streptococci (Streptococcus pyogenes), but until lately immunity was thought to
      be strain-specific and dependent on antibodies to the variable serotype-specific
      regions of the protein. Experiments in animals have suggested the conserved
      region of the M protein as a possible alternative target for protective
      antibodies. We constructed a 20-aminoacid peptide (peptide 145) within the
      conserved region of the carboxyl terminus of the protein. In mice the peptide
      induced serum antibodies that could opsonise reference type 5 streptococci. By
      enzyme-linked immunosorbent assay, positive responses to peptide 145 were
      obtained with serum from 77 (90%) of 86 Aboriginal subjects and 135 (81%) of 167
      Thai subjects living in areas with high exposure to streptococci. Only 10 (14%)
      of 71 Caucasian subjects with low exposure to streptococci showed positive
      responses. There was no difference in the proportion positive between subjects
      with rheumatic heart disease and control groups (other or no heart disease).
      Antibodies to peptide 145 were able to opsonise isolates of streptococci from
      Aboriginal and Thai subjects with acute rheumatic fever as well as reference
      strains. This highly conserved part of the M protein may be a suitable target for
      vaccines to prevent streptococcal infections and their sequelae.

PMID- 7520964
TI  - Risperidone in Parkinson's disease.

PMID- 7520965
TI  - The effect of decongestive nosedrops on human respiratory mucosa in vitro.
AB  - The aim of this study was to investigate the morphological effects of
      decongestive drops and sprays on human respiratory mucosa in vitro. Precultured
      fragments of adenoid tissue in a specially designed tissue culture system were
      exposed to decongestive preparations for 10 minutes once a day for 10 days.
      Tissue exposed to preparations preserved with benzalkonium chloride and tissue
      exposed to benzalkonium chloride alone underwent severe morphological
      alterations. Unpreserved decongestive substances did not have this effect.
      Benzalkonium chloride is a well-documented toxic substance in several respects.
      Supported by previous studies, it may seem unfortunate to use it as an additive
      in decongestive preparations.

PMID- 7520968
TI  - Tacrolimus (FK506) for organ transplants.

PMID- 7520966
TI  - Arginine supply for nitric oxide synthesis and arginase is mainly exogenous in
      elicited murine and rat macrophages.
AB  - L-arginine, the precursor of nitric oxide(NO) is provided mainly by extracellular
      sources in casein-elicited murine and rat peritoneal macrophages. Free
      extracellular L-arginine(Arg), esters, peptides and proteins containing Arg are
      the best sources in accordance with the fact that proteolytic activity is high in
      peritoneal macrophages. The recycling of Arg from citrulline(Cit) was observed
      but at a low rate. This situation is different from that in endothelial cells
      where half of Arg is recycled from citrulline. No significant anaplerotic
      reaction from glutamic acid(Glu) can be demonstrated in peritoneal macrophages.

PMID- 7520967
TI  - Role of K+ channel opening and Na(+)-K+ ATPase activity in airway relaxation
      induced by salbutamol.
AB  - To determine the role of K+ channel opening and Na(+)-K+ ATPase activity in the
      beta-adrenoceptor-mediated relaxation of airway smooth muscle, we studied canine
      bronchial segments under isometric conditions in vitro. Relaxant responses to
      salbutamol were not altered by glibenclamide or apamin but inhibited by
      charybdotoxin, where significant inhibition was observed only at salbutamol
      concentrations of less than 10(-6) M. In contrast, only the relaxations induced
      by salbutamol at 3 x 10(-6) M and greater were sensitive to ouabain. Relaxations
      produced by low and high concentrations of salbutamol were selectively attenuated
      by charybdotoxin and ouabain, respectively, in a concentration-dependent manner.
      These results suggest that both Ca(2+)-activated K+ channel and Na(+)-K+ ATPase
      may be operative in the airway relaxation induced by low and high concentrations
      of the beta-adrenergic agonist, respectively.

PMID- 7520970
TI  - [Aprotinin and monitoring of heparin level during cardiopulmonary bypass:
      preliminary report].

PMID- 7520969
TI  - [A monoclonal antibody reactive with human squamous cell carcinoma of the
      esophagus].
AB  - Monoclonal antibody KYSM-1, whose immunoglobulin was IgM, was produced against
      human esophageal squamous cell carcinoma (KE-1) which has been maintained by
      serial subcutaneous transplantation in nude mice. In immunohistochemical
      reactions with various cancer tissues, KYSM-1 showed a strong reaction specific
      to squamous cell carcinomas of the esophagus, oral cavity and lung (92%, 95/103
      and 100%, 3/3 and 100%, 7/7), with the lack of gastrointestinal adenocarcinomas
      and pulmonary nonsquamous cell carcinomas (small cell and large cell carcinomas).
      In contrast to this result, no reaction was recognized in several normal tissues,
      such as the lung, stomach, colon, liver, spleen, lymph node, pancreas, kidney,
      and mammary gland, however, a weak reaction was found in the basal layer of the
      esophageal mucosa. Antigenetic determinant of squamous cell carcinoma reactive
      with KYSM-1 was revealed to be protein moiety after enzyme treatment, and
      molecular weight of the antigen was about 60,000 analysed by Western blotting.
      These results suggest that KYSM-1 may be useful for not only immunoscintigraphy
      but also for the targeting chemotherapy.

PMID- 7520971
TI  - Chromosome specific c-DNA libraries: reduction of unspecific priming events by
      purification of heteronuclear RNA.
AB  - Chromosome specific c-DNA libraries greatly facilitate the isolation of disease
      associated genes which have been previously linked to particular chromosomes.
      Recently, several methods have been developed and employed for the isolation of
      transcribed sequences from specific human chromosomes and chromosome regions.
      Heteronuclear (hn) RNA from somatic human/rodent cell hybrids has been used as
      starting material to selectively prime the synthesis of human specific c-DNAs. A
      drawback of this method is the high number of rodent clones found in these
      chromosome specific c-DNA libraries. Here, we provide direct evidence that
      unspecific priming events account for the majority of these rodent clones. Using
      an Alu consensus primer hn-RNA human specific c-DNA libraries have been
      established and the specificity of Alu-priming has been evaluated. Using a
      variety of purification schemes for isolating hn-RNA we have significantly
      reduced the percentage of unspecific priming events. We also included a
      comparison of the hn-RNA yield from different somatic hybrids prior and after
      purification.

PMID- 7520973
TI  - Modulatory effect of sodium butyrate on AluI-induced chromosomal aberrations in
      CHO cells.
AB  - Exponentially growing CHO cells exposed to millimolar concentrations of sodium
      butyrate (SB) for 24 h were treated with AluI using two methods of cell poration,
      i.e., electroporation and streptolysin O (SLO). Under both conditions, SB was
      found to induce a 2-4-fold increase in AluI-induced chromosomal aberrations. When
      cells in monolayer were treated with AluI/SLO, lower concentrations of SB (2.5
      mM) and AluI (1-4 U/ml) were required to produce a similar effect as that
      observed for electroporated cells, demonstrating the differential sensitivity of
      the two methods. Furthermore, in AluI/SLO-treated cells, a higher percentage of
      cells was found to show increased frequencies of aberrations per cell, compared
      to AluI/electroporated cells. The mechanism by which SB modulates the cell
      response to AluI treatment might involve changes in chromatin configuration
      thereby increasing the accessibility of AluI to different parts of chromatin.

PMID- 7520972
TI  - DNA sequence analysis of gamma-radiation (anoxic)-induced and spontaneous lacId
      mutations in Escherichia coli K-12.
AB  - An extensive spectrum of ionizing radiation mutagenesis was determined by
      sequencing 318 137Cs gamma-radiation (anoxic)-induced episomal lacId mutations in
      Escherichia coli strain NR9102. The most commonly found radiation-induced
      mutations were base substitutions (44% transversions and 41% transitions). The
      radiation-induced spectrum consisted of: 23% G.C-->A.T, 18% A.T-->G.C, 17% G.C-
      >T.A, 14% G.C-->C.G, 8% A.T-->T.A, 6% A.T-->C.G, 8% single-base deletions, 5%
      multiple mutations, 3% multi-base deletions, and essentially no single- or multi
      base additions. This spectrum compared better with spectra for other systems
      obtained by in vivo irradiation than with one obtained by in vitro irradiation.
      Multiple mutations, which were unique to the radiation-induced spectrum,
      generally consisted of one active and one closely linked silent mutation, and are
      suggested to result from an altered replication complex of reduced fidelity.
      Mutation rates were 4.1 x 10(-8) lac-constitutive mutations/gene/Gy and 1.2 x 10(
      10) base substitutions/base pair/Gy. Thirty-two percent more radiation-induced
      mutations occurred at G.C vs. A.T base pairs. A strand asymmetry was noted for
      G.C-->C.G and A.T-->T.A transversions. A nearest-neighbor analysis showed that C
      (vs. A, G, or T), on either side of the mutation site, substantially enhanced
      most types of base substitutions. Similarly, G and C flanked both sides of single
      base deletion sites twice as frequently as would be expected from the base
      composition of the mutation target. For comparative purposes, we sequenced 411
      spontaneous lac-constitutive mutants of which 269 were lacId mutants, and there
      was good agreement between these and previously published mutational spectra. The
      spontaneous and radiation-induced mutational spectra differed substantially for
      virtually every class of mutation. For example, the set of spontaneous dominant
      lac-constitutive mutations contained many more mutations that did not map in the
      normal region for lacId mutations (i.e., 35% vs. 3%) and were presumed to be lacO
      constitutive mutations. A sampling of these presumptive lacOc mutations was also
      sequenced: 17/22 (spontaneous) and 1/9 (radiation) were found to be lacOc long
      deletions, one from each set were base substitutions, and the remaining mutations
      showed the wild-type lacO sequence. Like the radiation-induced spectrum, the
      spontaneous spectrum showed enhanced mutagenesis at G.C sites, strand asymmetry,
      and enhanced mutagenesis when G or C were the nearest neighbors.

PMID- 7520974
TI  - Defective transformation of chromosomal markers in DNA polymerase I mutants of
      the radioresistant bacterium Deinococcus radiodurans.
AB  - The transformation efficiency of six independently selected chromosomal markers
      (four for rifampicin resistance and two for acriflavine resistance) was found to
      be reduced by about 3 logs in a Deinococcus radiodurans strain that was isogenic
      with wild type except for an insertional mutation in the pol gene that eliminated
      DNA polymerase I activity (strain 6R1A). D. radiodurans strains UV17 and 303,
      previously obtained by chemical mutagenesis, were determined to be partially
      deficient in DNA Pol I activity as assessed in a permeabilized cell system. Both
      UV17 and 303 demonstrated intermediate transforming efficiencies that correlated
      with their levels of residual polymerase activity. The transformation efficiency
      of strain 6R1A could be greatly restored by expression of cloned E. coli DNA Pol
      I, but not to wild-type levels. Plasmid transfer and chromosomal duplication
      insertion were not substantially affected by lack of DNA Pol I activity. D.
      radiodurans is known to possess extraordinarily efficient repair pathways for DNA
      damage, and is refractory to DNA damage-induced mutagenesis caused by numerous
      agents, including several that cause base mispairing. We suggest that D.
      radiodurans may differ from other naturally transformable bacteria in that DNA
      Pol I is needed to efficiently convert most drug-resistance markers. This unusual
      mechanism may be required to accomplish chromosomal conversion prior to
      correction of donor DNA by this organism's efficient repair pathways.

PMID- 7520975
TI  - Chromosome damage in PUVA-treated human lymphocytes is related to active oxygen
      species and clastogenic factors.
AB  - Besides the direct interaction of psoralens with DNA and other macromolecules,
      the role of reactive oxygen species in the PUVA-induced cellular injury has been
      stressed. The present study shows that treatment of human blood cultures with 5
      methoxypsoralen or 8-methoxypsoralen, followed by UVA exposure, results in
      chromosome damage. The supernatant of these cultures contains secondarily formed
      chromosome damaging material, called clastogenic factor (CFs). Not only CF
      formation, but also CF action is inhibited by superoxide dismutase (SOD),
      suggesting that superoxide is formed on the pathway to chromosome aberration. CF
      is detectable in the cell culture supernatants after a minimal delay of 18 h, and
      reaches a plateau at 24 h of cultivation. SOD is no longer protective if added
      after 24 h, i.e., the enzyme can prevent, but not repair the oxyradical-induced
      damage.

PMID- 7520977
TI  - Antimutagenicity of three isomers of aminobenzoic acid in Salmonella typhimurium.
AB  - The m-, o- and p-isomers of aminobenzoic acid (ABA) repressed the mutagenicity of
      N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium TA100.
      Their antimutagenic potency was in the order of o-ABA > m-ABA > p-ABA. The
      mechanism of this antimutagenicity is ascribed mainly to the decomposition of
      MNNG induced by the aminobenzoic acid isomers outside or within the bacterial
      cells. The inhibition of plant cell peroxidases and bacterial acetyltransferases
      that are required for the plant activation of 2-aminofluorene (2-AF) to mutagenic
      product(s) may participate in the repression of 2-AF mutagenesis by the
      aminobenzoic acids in S. typhimurium strain YG1024. The aminobenzoic acid isomers
      exhibited no inhibitory effects towards the direct-acting agent 2-acetoxy-2
      acetylaminofluorene, the stable diacetylated metabolic product of 2-AF.

PMID- 7520976
TI  - Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral
      blood lymphocytes after occupational exposure to antineoplastic agents.
AB  - In this study we have compared the results of a method for the detection of
      cyclophosphamide in urine and the results of analysis of chromosomal aberrations
      in peripheral blood lymphocytes of four groups of subjects with various exposure
      statuses. These groups are 17 Dutch and 11 Czech exposed workers (mainly hospital
      nurses and pharmacy technicians) handling antineoplastic agents and 35 Dutch and
      23 Czech controls (nurses, medical doctors, pharmacy and lab technicians) not
      handling these drugs. The groups were subdivided into smokers and non-smokers
      because of a confounding effect of smoking. Within the Dutch groups, the
      percentage of aberrant cells and the number of breaks per cell were increased for
      smokers compared to non-smokers. The percentage of aberrant cells was increased
      in Dutch exposed workers in comparison with Dutch control workers. Within the
      Czech groups the percentage of aberrant cells and the number of breaks per cell
      were increased in exposed workers in comparison with control workers. However,
      both Dutch and Czech smokers mainly contributed to the increase. The results
      suggest an additive effect of exposure and smoking in the Dutch subjects and a
      more than additive effect in the Czech subjects. In urine samples of three out of
      11 Dutch exposed workers cyclophosphamide was found in a range of 0.1-0.5
      micrograms/24 h. Higher levels were detected in the urine of eight out of 11
      Czech exposed workers, a range of 0.1-2.9 micrograms/24 h. No correlation was
      observed between the amounts of cyclophosphamide excreted in urine on the one
      hand and the percentage of aberrant cells and the number of breaks per cell on
      the other hand. The present study is the first study showing that hospital
      workers having an increase in chromosome aberrations related to their work are
      exposed to at least one antineoplastic agent.

PMID- 7520979
TI  - Inhibition of the clastogenic effect of cyclophosphamide by WR-2721 in the bone
      marrow of mice.
AB  - The frequency of micronucleated polychromatic erythrocytes in the bone marrow of
      Swiss mice treated with WR-2721, at a dose of 200 mg/kg or 400 mg/kg body weight,
      15 or 30 min prior to cyclophosphamide (CP) administration, at a dose of 200
      mg/kg body weight, was determined 24 h after CP treatment. In mice injected with
      CP, the number of micronuclei in polychromatic erythrocytes was significantly
      increased in comparison with the controls, and in mice treated with WR-2721 and
      CP, the frequency of micronucleated polychromatic erythrocytes was distinctly
      decreased in comparison to those given CP alone. The protective effect of WR-2721
      against cyclophosphamide-induced clastogenicity was shown. The effect was
      dependent on the dose of the thiol agent given, and it was more expressed when WR
      2721 was applied at the higher dose, 400 mg/kg body weight. However, the
      protection by the aminothiol appeared not to depend on the time intervals between
      WR-2721 and CP administration to the mouse organism.

PMID- 7520980
TI  - The groE gene products of Escherichia coli are dispensable for mucA+B(+)
      dependent UV mutagenesis.
AB  - UV mutagenesis in Escherichia coli requires the groES+EL+ chaperonins as well as
      the umuD+C+ SOS-regulated genes. GroES and GroEL appear to be required to
      stabilize UmuC. The mucA+B+ genes, which are encoded on a broad host range
      plasmid, are functionally analogous and structurally similar to the umuD+C+ genes
      of E. coli. While these gene pairs are quite similar, differences have been
      reported in the functioning of these gene products. We tested whether mucA+B+
      function requires the groE+ gene products as well. We show that mucA+B(+)-induced
      UV mutagenesis, UV resistance, phage reactivation and cold sensitivity do not
      require the groE+ heat shock genes. These findings suggest that the requirement
      of UmuC for groES+EL+ function is not shared by its analog, MucB.

PMID- 7520978
TI  - Combination treatments of Chinese hamster ovary cells with various restriction
      endonucleases result in chromosomal aberrations whose frequencies are additive or
      less than additive.
AB  - Chinese hamster ovary cells were treated with combinations of different
      restriction endonucleases (RE). The frequencies of chromosomal aberrations after
      combination treatments were additive or less than additive when compared with the
      effects of the single RE. These data indicate that DNA double-strand breaks (DSB)
      induced by different types of RE in combination treatments lead to chromosomal
      aberrations in the same way as DSB induced by single RE.

PMID- 7520981
TI  - Effects of thymidine kinase and methyltransferase deficiency on mutagenesis in a
      human lymphoblastoid cell line.
AB  - In this study the effect of thymidine kinase (TK) deficiency on mutagen
      sensitivity was examined in the human lymphoblastoid cell line Raji. Wild-type
      and TK-deficient Raji cells were treated with a range of concentrations of ethyl
      methanesulphonate (EMS) and a range of doses of ultraviolet (UV) light, then
      examined for mutagen sensitivity as measured by cell survival and mutation to
      HGPRT deficiency. Dose-dependent responses were observed and TK-deficient cells
      exhibited decreased survivals and increased mutant frequencies relative to wild
      type cells. TK-deficient Raji cells are also deficient in O6-methylguanine-DNA
      methyltransferase. This may partially account for their sensitivity to EMS but
      does not account for the results obtained with UV. It is therefore likely that an
      additional factor, such as alterations in supply of deoxyribonucleoside
      triphosphates, may affect the mutagen sensitivity of Raji cells.

PMID- 7520982
TI  - Increased frequencies of micronuclei in early spermatids of rats following
      exposure of young primary spermatocytes to acrylamide.
AB  - The 'suspension method' for detection of micronuclei in early spermatids (Golgi
      phase 1 + 2) of rats was used to study induction of chromosomal damage in
      spermatocytes exposed to single (50 and 100 mg/kg) or fractionated (4 x 50 mg/kg;
      24-h intervals) doses of acrylamide. Animals were killed at different time
      intervals after treatment to measure induction of damage in different stages of
      spermatocyte development. A statistically significant enhancement of micronucleus
      frequencies was found after exposure of pre-leptotene spermatocytes to a single
      dose of 100 mg/kg (days 18 and 20 after treatment) or a fractionated dose of 4 x
      50 mg/kg (day 19). In the latter case there was also a significant effect in
      zygotene spermatocytes that were sampled 15 days after treatment. Comparative
      studies indicated that the original 'suspension method' can be simplified by
      omitting enzyme treatments for the release of germ cells from the seminiferous
      tubules. In the present acrylamide study the old and new procedures gave similar
      results.

PMID- 7520983
TI  - The spermatid micronucleus test with the dissection technique detects the germ
      cell mutagenicity of acrylamide in rat meiotic cells.
AB  - As a part of the development and validation of the spermatid micronucleus test
      (SMNT) in the project 'Detection of Germ Cell Mutagens' sponsored by the CEC we
      studied the mutagenicity of acrylamide (AA) and mitomycin C (MMC). Of two
      alternative techniques, we used the 'dissection technique' based on
      microdissection of seminiferous tubules offering a narrow window for evaluation
      of cell stage sensitivity, and including DNA-specific staining and scoring. AA
      given as a single injection of 50 or 100 mg/kg did not significantly increase MN
      frequencies. When a subchronic treatment (4 x 50 mg/kg) was given, a significant
      increase over background was observed 18 and 19 days after the last injection,
      indicating genotoxic activity in preleptotene spermatocytes and late
      spermatogonial stages. MMC given as single injections of 0.5 or 1.0 mg/kg
      increased MN frequencies significantly 17, 18, 19 and 20 days after treatment as
      a result of clastogenicity in S phase cells. DNA flow cytometry did not show
      cytotoxicity of AA to preleptotene spermatocytes, but a small decrease in the
      numbers of stem cells. If spindle disturbances are caused by AA, as suggested,
      they were not detectable by induction of spermatid MN in vivo 1 or 3 days after
      treatment or by treatment with AA of cultured segments of seminiferous tubules
      undergoing meiotic divisions in vitro. In conclusion, the SMNT with the
      dissection technique is able to show the germ cell clastogenicity of AA and MMC.
      AA was observed to have a much weaker MN inducing potency than MMC.

PMID- 7520984
TI  - Weak genotoxicity of acrylamide on premeiotic and somatic cells of the mouse.
AB  - The effects of acrylamide (AA) were evaluated, under the EEC/STEP project
      'Detection of Germ Cell Mutagens', by carrying out several cytogenetic assays on
      mouse germ and somatic cells. The spermatid micronucleus (MN) test was applied
      after treatment of meiotically dividing or premeiotic S phase cells. Acute
      treatments (50 and 100 mg/kg i.p.) as well as subchronic exposure to AA (4 x 50
      mg/kg, 4 i.p. injections at 24-h intervals) were performed. A weak increase of MN
      was induced only by treatment with AA of cells in S phase. Sister-chromatid
      exchange (SCE) analysis in differentiating spermatogonia treated i.p. with 50 and
      100 mg/kg confirmed the weak genotoxicity of AA in the premeiotic stages of
      spermatogenesis. The application of the MN test in peripheral blood reticulocytes
      of the same animals used for the spermatid MN assay indicated that the
      cytogenetic effects induced by AA in the somatic and the germ cell lines are
      comparable in magnitude. The results obtained in this study by applying the
      spermatid micronucleus assay are in very good agreement with those reported by
      two other laboratories with the same technique.

PMID- 7520986
TI  - Dose response for heritable translocations induced by acrylamide in spermatids of
      mice.
AB  - A heritable translocation test was carried out with acrylamide (AA) to obtain a
      dose-response relationship for induction of reciprocal translocations in late
      spermatids of the mouse. Male C3H/E1 mice were treated with single i.p. doses of
      50 and 100 mg/kg of acrylamide and mated 7-16 days after treatment to untreated
      female 102/E1 mice. Translocation carriers among the F1 progeny were selected by
      a sequential procedure of fertility testing and cytogenetic analysis including G
      band karyotyping to determine the chromosomes involved in the respective
      translocations. The translocation frequencies observed with 50 mg/kg and 100
      mg/kg of AA were 0.6% and 2.7%, respectively. The historical control
      translocation frequency was 0.04%. Doubling dose estimates based on these and
      previous data are discussed.

PMID- 7520985
TI  - Acrylamide-induced chromosomal damage in male mouse germ cells detected by
      cytogenetic analysis of one-cell zygotes.
AB  - Within a project coordinated by the Commission of the European Communities for
      the detection of germ cell mutagens, the cytogenetic analysis of first-cleavage
      metaphases was carried out to detect chromosomal damage induced by acrylamide
      (AA) in meiotic and postmeiotic stages of mouse spermatogenesis. Male mice were
      intraperitoneally injected with single acute doses of 75 or 125 mg/kg or treated
      with five daily injections of 50 mg/kg and mated either 7 or 28 days after the
      end of treatment. Chromosomal aberrations were scored in C-banded metaphases
      prepared from one-cell zygotes by a mass harvest technique. AA treatment of late
      spermatids-spermatozoa resulted in significant increases of structural
      aberrations at all doses tested. The data could be fitted to a curvilinear
      regression and a doubling dose of 23 mg/kg was calculated. The large majority of
      observed aberrations were of the chromosome type, including dicentrics, rings and
      translocations, in agreement with a mechanism of chromosomal damage mediated
      through the alkylation of DNA-associated protamines. Even though the frequency of
      aberrations 28 days after treatment was not significantly higher than the control
      value, the presence of multiple rearrangements in two cells suggested that AA
      might also have a minor effect on spermatocytes. The results of the cytogenetic
      analysis of first cleavage metaphases agreed well both qualitatively and
      quantitatively with the outcome of dominant lethal and heritable translocation
      assays. AA-induced cytotoxicity was monitored by flow cytometric DNA content
      analysis of testicular cells. By this method, a dose-dependent depletion of
      mature spermatids after treatment of spermatogonia and a toxic effect upon
      primary spermatocytes were detected.

PMID- 7520987
TI  - 1,3-butadiene is a somatic and germ cell mutagen: a preface to research papers.

PMID- 7520988
TI  - Dominant lethal effects after inhalation exposure to 1,3-butadiene.
AB  - Two independent dominant lethal experiments were performed using different
      protocols with respect to strains of mice, inhalation exposure duration of 1,3
      butadiene, and mating regimen. The short communication summarizes the results of
      the experiments and compares the induced dominant lethality according to the
      formula published by Ehling in 1978. Despite the differences in methodology the
      results are in close agreement. The sum of the dominant lethal effects observed
      during the first three mating weeks after 1 week of butadiene exposure in one
      experiment (23.1%) is surprisingly similar to the dominant lethal effect observed
      during 1 week of mating after 10 weeks of butadiene exposure (28.1%) in the other
      experiment. The results of the two independent experiments strengthen the
      conclusion that butadiene is a germ cell mutagen. Furthermore, the results
      indicate that the effect observed after 10 weeks of exposure is representative of
      the last three treatment weeks, i.e. treated spermatozoa and spermatids.

PMID- 7520989
TI  - Development of a cloning assay with high cloning efficiency to detect induction
      of 6-thioguanine-resistant lymphocytes in spleen of adult mice following in vivo
      inhalation exposure to 1,3-butadiene.
AB  - A cloning assay with high cloning efficiency has been developed to detect
      spontaneous and induced 6-thioguanine-resistant T-lymphocytes (HPRT mutants) from
      the spleen of adult mice. The mean cloning efficiency in untreated male mice of
      20-22 weeks old was 34.5 +/- 11.2% (SD) and the corresponding mutant frequency
      0.7 +/- 0.8 (SD) x 10(-6). The cloning efficiencies obtained in this study are
      substantially higher than those reported previously by other investigators. Using
      this assay, it could be demonstrated that inhalation exposure of mice to 200, 500
      or 1300 ppm of 1,3-butadiene for 6 h/day on 5 consecutive days caused a
      statistically significant induction of 6-thioguanine-resistant mutations in T
      lymphocytes from spleens of adult mice exposed to 1300 ppm. The exposure to 1300
      ppm resulted in a three-fold increase of the spontaneous mutant frequency. The
      mutant frequency after exposure to 500 ppm was higher than the control but the
      increase was not significant.

PMID- 7520990
TI  - Mutagenicity of 1,3-butadiene inhalation in somatic and germinal cells of mice.
AB  - Inhalation exposure of mice to 50, 200, 500 or 1300 ppm of 1,3-butadiene for 6 h
      per day for 5 consecutive days caused micronuclei in mouse bone marrow and
      peripheral blood erythrocytes. The dose response was non-linear. The slope of the
      curve flattened with increasing exposure concentration. Coat color spots were
      found in the mouse spot test after exposure of pregnant females on pregnancy days
      8-12 to 500 ppm of 1,3-butadiene. Dominant lethal mutations were induced in
      spermatozoa and late spermatids after exposure of male mice to 1300 ppm with the
      5-day exposure regimen. Thus, in the mouse 1,3-butadiene is a somatic and germ
      cell mutagen.

PMID- 7520991
TI  - Induction of micronuclei in peripheral blood and bone marrow erythrocytes of rats
      and mice exposed to 1,3-butadiene by inhalation.
AB  - Female CB6F1 mice and male Wistar rats were exposed to different concentrations
      of 1,3-butadiene (1,3-BD) by inhalation. Micronucleus tests using both peripheral
      blood erythrocytes and femoral marrow cells of these animals were performed.
      Cells were stained either using conventional acridine orange (AO) staining or
      supravitally using AO-coated slides. Dose-dependent increases in the frequency of
      micronuclei (MN) were observed both in blood and in bone marrow cells in mice.
      1,3-BD did not, however, increase the frequency of MN in either blood or bone
      marrow cells of rats at any of the tested concentrations.

PMID- 7520992
TI  - Human cytogenetic biomonitoring of occupational exposure to 1,3-butadiene.
AB  - The association of occupational exposure to 1,3-butadiene and chromosomal damage
      in peripheral blood lymphocytes was studied in 40 workers from two production
      facilities. Control persons, 30 in all, were chosen from other departments of the
      same plants, and they were roughly matched for age and smoking habits. The
      exposure levels to ambient butadiene were measured both by personal sampling
      using diffuse monitors and by stationary sampling at production and handling
      sites. Chromosome aberrations (CA), micronuclei (MN) and sister-chromatid
      exchanges (SCE) in peripheral lymphocytes were analyzed as markers of exposure.
      Smoking had a slight effect on the frequency of MN, and the mean frequency of
      SCEs was also higher in smokers than in non-smokers. No effect of smoking,
      however, was seen in relation to chromosomal aberrations. No exposure related
      effects were seen in any of the three cytogenetic endpoints in either of the
      butadiene production plants, representing typical low (below 3 ppm) exposure
      levels of the butadiene manufacturing industry.

PMID- 7520993
TI  - Mutagenesis resulting from DNA damage by lipid peroxidation in the supF gene of
      Escherichia coli.
AB  - In vitro incubation of rat microsomal lipids with NADPH and Fe3+ in the presence
      of cytochrome P450 reductase produces lesions in double-stranded pZ189 plasmid
      DNA, the mutagenic potential of which was analyzed after transfection into
      Escherichia coli host cells that had been induced for SOS functions by
      ultraviolet irradiation. The extent of lipid peroxidation, when monitored by the
      formation of thiobarbituric acid reaction substances, was increased with
      increased addition of lipids in the reaction mixture. Mutagenesis was determined
      with the forward mutation assay using the supF gene of pZ189 as a target. When
      treated pZ189 DNA was used to transfect host cells, a seven-fold increase in
      mutation frequency for SOS uninduced hosts and a 12-fold increase in mutation
      frequency for SOS induced hosts was observed at 50% survival compared to that
      observed with untreated DNA. Sequence analysis shows that incubation of pZ189 DNA
      in the lipid peroxidation reaction mixture results mostly in single base
      substitutions, the most frequent base change being G:C-->C:G transversion,
      followed by G:C-->T:A transversion. The fact that, in the SOS induced hosts, the
      spectrum obtained by lipid peroxidation is similar to that of hydrogen peroxide
      suggests the possible involvement for mutagenesis of superoxide produced during
      lipid peroxidation, but not lipid peroxidation end products such as aldehyde or
      alkane. Treatment of pZ189 DNA with increasing extents of lipid peroxidation did
      not yield increasing formation of 8-hydroxyguanine. The results suggest that the
      origins of G:C-->C:G and G:C-->T:A transversions may be (an) as yet unidentified
      lesion(s) generated by lipid peroxidation.

PMID- 7520994
TI  - Hyperrecombination in pneumococcus: A/G to C.G repair and requirement for DNA
      polymerase I.
AB  - During pneumococcal transformation, we had previously described that the ami36
      mutation, which results from a C.G to A.T transversion, induces a large excess of
      wild-type recombinants in two point crosses. Upon donor-recipient DNA
      recombination, two heteroduplexes are generated by this mutation: A36/G+ and
      C+/T36. In two point crosses, hyperrecombination is observed only when
      transformation leads to the A/G mismatch. Here, we have studied the separate
      evolution of A36/G+ and C+/T36 heterozygotes created upon transformation of an
      ami36 mutant strain with artificial heteroduplex DNAs. We found that the A36/G+
      mismatch leads to a preferential generation of wild-type progeny as compared with
      the complementary C+/T36 mismatch. This result suggests that A/G carrying
      transformants partly behave as wild-type homozygotes. The only way to account for
      such behavior is an excision repair correcting some A/G mispairs created upon
      transformation into C.G pairs. Moreover, we show that hyperrecombination
      triggered by ami36 is strongly reduced in a DNA polymerase I deficient strain.
      This strengthens the fact of DNA repair synthesis, which should be therefore
      prominently due to DNA polymerase I.

PMID- 7520995
TI  - Induction of the genes RAD54 and RNR2 by various DNA damaging agents in
      Saccharomyces cerevisiae.
AB  - The relationship between the induction of the genes RAD54 and RNR2 and the
      induction and repair of specific DNA lesions was studied in the yeast
      Saccharomyces cerevisiae using Rad54-lacZ and RNR2-lacZ fusion strains. Gene
      induction was followed by measuring beta-galactosidase activity. At comparable
      levels of furocoumarin-DNA photoadducts, RAD54 was more effectively induced by
      bifunctional than by monofunctional furocoumarins indicating that mixtures of
      monoadducts (MA) and interstrand cross-links (CL) provide a stronger inducing
      signal than MA. RNR2 induction kinetics were measured in relation to cell growth
      and survival responses after treatment with the furocoumarins 8-methoxypsoralen
      (8-MOP), 5-methoxypsoralen (5-MOP), 3-carbethoxypsoralen (3-CPs), 7-methyl
      pyrido[3,4-c]psoralen (MePyPs) and 4,4',6-trimethylangelicin (TMA),
      benzo[a]pyrene (B(a)P and 1,6-dioxapyrene (1,6-DP) plus UVA, 254 nm UV radiation
      and cobalt-60 gamma-radiation. Induction of RNR2 took place during the DNA repair
      period before resumption of cell growth and clearly increased with increasing
      equitoxic dose levels. Treatments with furocoumarin plus 365 nm radiation (UVA)
      and 254 nm (UV) radiation were effective inducers whereas gene induction was
      relatively weak after gamma-radiation and absent after the induction of oxidative
      damage by B(a)P and 1,6-DP and UVA. The results suggest that it is the specific
      processing of different DNA lesions that determines the potency of the induction
      signal. Apparently, DNA lesions such as CL, and probably also closely located MA
      or pyrimidine dimers in opposite DNA strands involving the formation of double
      strand breaks as repair intermediates, are most effective inducers.

PMID- 7520996
TI  - Sensitivity to nitrogen mustard in Saccharomyces cerevisiae is independently
      determined by regulated choline permease and DNA repair.
AB  - Sensitivity of yeast cells to the bifunctional alkylating agent nitrogen mustard
      (HN2) depends on two independently operating physiological mechanisms of cellular
      metabolism: dynamics of uptake of HN2 via choline permease, encoded in the gene
      HNM1/CTR, and repair of HN2-induced DNA damage. Uptake of choline and HN2 is
      impaired in mutant alleles of HNM1/CTR, leading to a HN2 hyper-resistant
      phenotype. Overexpression of HNM1/CTR leads to HN2 sensitivity higher than that
      of the wild type. While mutation and regulation of HNM1/CTR have pronounced
      effects on the cell's HN2 sensitivity, they do not interfere with repair of HN2
      induced DNA damage, a process whose quality independently determines a yeast
      cell's sensitivity to HN2. Consequently, HNM1/CTR overexpression in an excision
      repair-deficient strain leads to extreme HN2 sensitivity whereas a mutational
      block of HNM1/CTR, in combination with excision proficiency, yields a HN2 hyper
      resistant phenotype.

PMID- 7520997
TI  - Validation of a flow cytometric in vitro DNA repair (UDS) assay in rat
      hepatocytes.
AB  - An in vitro flow cytometric (FCM) DNA repair assay has been developed and
      validated by comparison to conventional autoradiography (ARG). Both assays
      measure unscheduled DNA synthesis (UDS). Cultures of hepatocytes from young male
      Sprague-Dawley rats were exposed to a battery of 26 chemicals plus
      bromodeoxyuridine (BrdUrd) or 3H-thymidine (3H-dT) for 18-20 h before harvest.
      Selection of test chemicals was based upon both their genotoxicity
      classifications and carcinogenicity bioassay results in male rats. DNA repair in
      chemically treated cultures was detected flow cytometrically by measuring the
      uptake of BrdUrd in non-replicating (G1, G2, mitotic and 4C) cells. Intracellular
      levels of incorporated BrdUrd were visualized by immunochemical labeling with
      fluorescein isothiocyanate (FITC), and total cellular DNA content was
      simultaneously estimated by counterstaining samples with the nucleic acid
      intercalator, propidium iodide (PI). Information was obtained from 10(4)
      cells/sample. Since repairing cells incorporate significantly less BrdUrd per
      unit of time than replicating cells, low intensity BrdUrd-FITC fluorescent
      signals from repairing cells are readily discriminated from high intensity
      signals from replicating cells when displayed on linear univariate histograms.
      Further distinction between repairing and replicating cells was achieved by
      displaying the DNA contents of all cells on linear bivariate histograms. Thus,
      repairing cells were resolved without subjecting these cultures to agents which
      suppress replicative synthesis (e.g., hydroxyurea). Results from these concurrent
      FCM and ARG investigations include the following: (1) conclusions (DNA repair
      positive or negative) were in agreement, with one exception, cinnamyl
      anthranilate, for which cytotoxic doses produced a positive FCM response, but
      lack of intact hepatocytes in parallel ARG preparations prevented analysis; (2)
      similar sensitivities for most of the positive chemicals were reported; (3) a
      high correlation (85%) exists between the reported genotoxicity classification
      and these DNA repair results in the absence of overt cytotoxicity; (4) a poor
      correlation exists between these DNA repair results and hepatocarcinogenesis
      (only 4/11 liver carcinogens tested positive) or overall carcinogenesis in the
      male rat (only 9/21 carcinogens tested positive). This FCM assay provides a
      rapid, sensitive, safe and reliable means of identifying agents which induce DNA
      repair in mammalian cells.

PMID- 7520999
TI  - DNA double-strand break rejoining in xrs5 cells is more rapid in the G2 than in
      the G1 phase of the cell cycle.
AB  - The radiosensitive xrs5 mutant cell line of CHO K1 shows an overall deficiency in
      DNA double-strand break (dsb) rejoining. However, xrs5 paradoxically shows an
      apparently normal rate of disappearance of chromatid breaks with time, the
      kinetics of which is thought to reflect the underlying rejoining of dsb.
      Nevertheless the yield of chromatid breaks is elevated by four-fold in xrs5. A
      possible explanation of the paradox might be that xrs5 is proficient in rejoining
      dsb in the G2 phase of the cell cycle but converts a higher number of dsb into
      chromatid breaks. In order to test this we have measured the rejoining of dsb in
      partially synchronised G2 xrs5 cells and compared the kinetics with those of
      cells synchronised in the G1 phase. Synchronisation of cells was achieved in G2
      by release of cells from an aphidicolin block, and in G1 by staurosporine block.
      Cell synchrony was monitored by cytofluorometry and showed typically a 67%
      synchronisation of G2 cells and a 91% synchronisation of G1 cells. Rejoining of
      dsb was measured using neutral filter elution at pH 9.6. G2 cells showed a two
      component kinetic with t1/2 values of 9 min and 3.6 h for dsb rejoining.
      Corresponding t1/2 values for G1 cells were 15 min and approximately 8.8 h. The
      t1/2 value of 3.6 h found for dsb rejoining in G2 cells is similar to a
      previously published value for asynchronous parental CHO K1 cells of
      approximately 4 h. The kinetics of chromatid break rejoining was measured in both
      xrs5 and CHO K1 following a dose of 0.75 Gy. The kinetics were found to be
      similar (t1/2 = 2.4 h) in the two cell lines, as previously reported using an
      equiclastogenic dose.

PMID- 7520998
TI  - DNA damage and stress protein synthesis induced by oxidative stress proceed
      independently in the human premonocytic line U937.
AB  - Heat shock proteins (HSPs) function as stress-inducible molecular chaperones and
      exert protective effects against cellular injury. The induction of the HSPs is
      considered to be mediated by the presence of abnormal proteins within the cell
      and/or by classical second messengers. Several lines of evidence have however
      suggested a relationship between DNA damage, HSP induction and thermotolerance.
      We investigated whether DNA alterations could represent a common signal for the
      induction of stress protein synthesis during heat shock or exposure to reactive
      oxygen species in the human premonocytic line U937. We measured, in parallel, DNA
      damage (both strand breaks and fragmentation) and HSP synthesis (by biometabolic
      labeling and Western blotting) after exposure to heat shock, hydrogen peroxide,
      bleomycin, cadmium or erythrophagocytosis. Heat shock induced DNA alterations
      along with HSP synthesis. In contrast, exposure to hydrogen peroxide or bleomycin
      induced DNA damage, but no HSP synthesis, suggesting that oxidation-induced DNA
      damage and HSP synthesis proceed independently in U937 cells. Erythrophagocytosis
      and cadmium induced the classical HSPs but no detectable DNA damage. Since these
      latter stresses also induced the oxidation-specific stress protein heme
      oxygenase, we suggest a protective role for heme oxygenase against oxidative DNA
      damage.

PMID- 7521000
TI  - Efficient synthesis of 32P-labeled single-stranded DNA probes using linear PCR;
      application of the method for analysis of strand-specific DNA repair.
AB  - We have developed a rapid method to synthesize radioactively labeled single
      stranded DNA probes suitable for strand-specific analysis of single copy genes on
      Southern blot. Linear PCR with 10 microCi alpha 32P-dATP (3000 Ci/mmol) as the
      only dATP source enabled us to generate strand-specific DNA probes with high
      specific activity. The probes synthesized by this method have higher specific
      activities and the same strand specificity compared to the end-labeled single
      stranded DNA probes obtained from single-stranded M13mp18/19 vectors. Application
      of the method for strand-specific analysis of ultraviolet-induced DNA lesions in
      defined DNA sequences significantly improved the hybridization signal.

PMID- 7521001
TI  - Excision of ultraviolet-induced photoproducts of 5-methylcytosine from DNA.
AB  - Transition mutations at DNA 5-methylcytosines, congregated at CpG islands, are
      implicated in the etiogenesis of human diseases. Formation of 5-methylcytosine
      hydrate (5-methyl-6-hydroxy-5,6-dihydrocytosine) by hydration of the 5,6 double
      bond of 5-methylcytosine has been suggested as an intermediate in a possible
      mechanism of deamination to thymine. Ultraviolet irradiation of DNA yields
      pyrimidine hydrates, which are removed by repair glycosylases. We have identified
      5-methylcytosine photoproducts following their excision from DNA by E. coli
      endonuclease III. Poly(dG-[3H]5-medC):poly(dG-[3H]5-medC) was irradiated and
      reacted with the enzyme. Radiolabeled photoproduct releases were directly
      proportional to irradiation doses and enzyme concentrations. These were
      identified as cis-thymine hydrate (6-hydroxy-5,6-dihydrothymine) and trans
      thymine hydrate. Recovery of thymine hydrates is consistent with hydration of
      pyrimidines. Subsequent heating (which converts thymine hydrates to thymines) and
      chemical sequencing of an irradiated, 3' end-labeled, synthetic DNA strand
      demonstrated the appearance of thymine at the 5-methylcytosine site. These
      results demonstrate a mechanism for deamination of DNA 5-methylcytosine via
      hydration of the 5,6 double bond, putatively yielding 5-methylcytosine hydrate;
      this deaminates to thymine hydrate, and loss of water yields thymine formation at
      the 5-methylcytosine site. Identification of these DNA 5-methylcytosine modified
      moieties indicates a possible molecular mechanism for the frequent transition
      mutations found at CpG loci.

PMID- 7521003
TI  - An age-related increase in the basal level of DNA damage and DNA vulnerability to
      oxygen radicals in the individual hepatocytes of male F344 rats.
AB  - Previous biochemical studies on pooled hepatocytes have provided a wealth of
      information concerning age-related changes in DNA damage and DNA vulnerability
      (susceptibility) to oxygen radicals and related oxidants, but these studies
      focused on the whole liver and not on individual hepatocytes. The present study
      was designed to clarify the DNA damage and DNA vulnerability to hydrogen peroxide
      in individual hepatocytes using single cell gel electrophoresis (comet assay), a
      method that measures DNA single-stranded breaks/alkali-labile sites in individual
      cells. Hepatocytes were prepared from the liver of young (6-11 months) and old
      (26-29 months) male Fischer 344 rats. DNA damage was induced by exposure to
      hydrogen peroxide (3 x 10(-5), 3 x 10(-3)%). Observation of each comet image
      (migration length of DNA (MLD)) was performed in a non-exposure status (basal
      level) and after exposure. The mean value of MLD was significantly increased
      (approximately 1.5-fold) in the old rats at the basal level (P = 0.009).
      Moreover, the proportion of highly DNA-damaged hepatocytes (MLD > 80 microns)
      increased significantly (approximately 2.5-fold) in advanced age (P = 0.02). The
      mean value of MLD after exposure to hydrogen peroxide was increased with its
      concentration, but no significant difference was observed in DNA vulnerability to
      hydrogen peroxide between young and old rats. However, the proportion of
      hepatocytes showing a markedly high DNA vulnerability (MLD > 140 microns) to
      hydrogen peroxide was significantly higher in the old rats than in the young
      rats. It is suggested that the age-related increase in DNA vulnerability to
      oxygen radicals and/or related oxidants in some subpopulations causes the
      increase in DNA damage in advanced age in the liver as a whole.

PMID- 7521004
TI  - Detection and quantitation by competitive PCR of an age-associated increase in a
      4.8-kb deletion in rat mitochondrial DNA.
AB  - Recent studies on human tissues have shown that the quantity of partially deleted
      mitochondrial DNA (mtDNA) increases with age. In this study, mtDNAs from the
      livers of young adult and old Wistar rats were analyzed by PCR. Evidence for
      partially deleted mtDNAs was found, with a 4834-bp deletion present in all
      animals and most easily detected in samples from senescent rats. The deletion
      breakpoint occurs at a 16-bp direct repeat present in the cytochrome oxidase I
      and ATPase 6 genes. This deletion in rats is similar in size and location to the
      5.0-kb deletion observed in human mtDNA. The proportion of rat mtDNA with this
      4.8-kb deletion was quantitated by a competitive PCR assay. The ratio of
      partially deleted mtDNA/total mtDNA in liver mtDNA from individual 6 month old
      rats ranged from 5 x 10(-6) to 3 x 10(-5), while the ratio in 24 month old rats
      ranged from 8 x 10(-4) to 5 x 10(-3), with a mean 100-fold increase with age.
      These increases are in the range observed for human mtDNA during aging. Thus
      senescent rats can be used as a model to study this type of mitochondrial DNA
      damage in aging. The method and reagents described should prove useful in studies
      of the mechanism(s) underlying deletions, their significance to the aging
      process, and testing of various compounds or interventions for their ability to
      slow the process.

PMID- 7521005
TI  - An investigation of mutation as a function of age in humans.
AB  - An accumulation of mutations on their own or together with other age-related
      changes may contribute to aging and the development of age-related pathologies.
      The aim of this investigation was to assess the extent of DNA mutations as a
      function of age in humans. The mutant frequency (MF) at the hypoxanthine-guanine
      phosphoribosyl-transferase (hgprt) locus was assessed in lymphocytes isolated
      from male volunteers in each of three age groups (35-39, 50-54 and 65-69 years).
      Results show that the mean MF in the 65-69 years group was approximately twice
      that in the 35-39 and 50-54 years groups (4.1/10(6) cells, 1.9/10(6) cells and
      1.79/10(6) cells, respectively) increasing by about 1.33% per year, after 54
      years. In addition, there was an increased frequency of chromosomal aberrations
      in the 65-69 years group compared to the other two age groups. The results of
      this investigation show an increase in DNA mutations in cultured human
      lymphocytes with age. Factors which may influence the extent of DNA damage in
      human lymphocytes are discussed.

PMID- 7521002
TI  - Somatic mutations at T-cell antigen receptor and glycophorin A loci in pediatric
      leukemia patients following chemotherapy: comparison with HPRT locus mutation.
AB  - Frequencies of somatic mutations in pediatric patients with leukemia were
      evaluated following intensive treatment at three different loci: the hypoxanthine
      guanine phosphoribosyl transferase (HPRT), T-cell antigen receptor (TCR), and
      glycophorin A (GPA) gene. Thirty-two children with acute lymphoblastic leukemia
      (ALL), nine children with acute myelogenous leukemia (AML), and 20 age-matched
      healthy controls were included in the study of mutant frequencies (Mfs) at the
      HPRT and TCR loci. Among these patients and controls, individuals with
      heterozygous MN blood type, i.e., 14 children with ALL, three children with AML,
      and nine healthy controls, served for the further assessment of variant frequency
      (Vf) at the GPA locus. In ALL patients, geometric mean Mfs and Vfs at these loci
      were significantly higher than in healthy controls. The high Mf value at the HPRT
      locus persisted for up to 8 years after the end of chemotherapy. On the other
      hand, the Mf values at the TCR locus and Vf values at the GPA locus declined
      gradually with time. In AML patients, on the other hand, the geometric mean Mf
      only at the TCR locus was significantly higher than in the controls, albeit to a
      lesser degree than in ALL patients. These data suggest that anti-cancer therapy
      induces somatic mutations at various loci and that ALL patients are more
      susceptible to mutagenic intervention than are AML patients.

PMID- 7521006
TI  - Effect of diet and vitamin C on DNA strand breakage in freshly-isolated human
      white blood cells.
AB  - We have measured DNA strand breaks induced by ionising radiation in nucleated
      cells from freshly isolated whole blood from normal human subjects. Samples were
      taken after subjects had fasted overnight and again 1 h after they had eaten
      breakfast in combination with approximately 35 mg/kg vitamin C. Damage was
      measured by single cell gel electrophoresis (the 'comet' assay), in which DNA
      single strand breaks generate a comet tail streaming from the nucleus. In repeat
      experiments on 6 subjects a reduction in DNA damage, as indicated by a highly
      significant decrease in overall comet length, was observed following vitamin C
      ingestion, both in the unirradiated control blood samples and in the dose
      response to ionising radiation damage. In addition, consistent differences in
      dose response between individual subjects were found. The peak effect was 4 h
      after intake of food and vitamin C. An effect was also seen with vitamin C alone
      and after breakfast without additional vitamin C. Protection against strand
      breakage was also seen in Ficoll-separated mononuclear cells but evidence was not
      obtained for protection of separated, mitogen stimulated T-lymphocytes either
      against ionising radiation cell killing in a clonal assay, or against
      clastogenicity assessed by micronucleus formation following one cell division.
      Exposure of separated lymphocytes in vitro to vitamin C, at doses greater than
      200 microM, did not offer protection but induced strand breakage. Our results
      raise the possibility that variation in normal diet may not only affect
      susceptibility to endogenous oxidative damage, but may affect some responses of
      the individual to radiation.

PMID- 7521007
TI  - Sequence organization and the mechanism of interstitial deletion clustering in a
      plant genome (Vicia faba).
AB  - Intercalary deletions and duplication-deletions are types of chromatid
      aberrations typical of the aberration spectrum observed in the first mitosis of
      plant cells after mutagen treatment. They are the results of error-prone
      recombination repair and arise when reunion is not prevented by inhibition of DNA
      synthesis. Both types of aberrations are nearly exclusively located in chromosome
      regions composed of tandemly arranged highly repetitive DNA sequences (e.g. FokI
      elements). The data discussed in the present paper make it possible to arrive at
      a simple mechanistic interpretation of the origin of these aberration types.

PMID- 7521008
TI  - Metabolic activation of nitrodibenzofurans by rat liver in
      Salmonella/mutagenicity test.
AB  - The effect of metabolic activation on the mutagenicity of nitrodibenzofurans
      (NDF) by rat liver S9 was evaluated with S. typhimurium tester strains. Except
      for 1-nitrodibenzofuran (NDF), five tested NDFs were mutagenic in strains TA98
      and TA98/1,8-DNP6 without S9 mix but were not mutagenic in strain TA98NR. NDFs
      mutagenized strain TA98NR with S9 mix, and the NAD(P)H system plus 3
      methylcholanthrene-induced S9 (3-MC-S9) was the most effective. The specificity
      of S9 enzyme(s) participating in the activation of NDFs was different from that
      of endogenous enzyme(s) in strain TA98, i.e., the order of mutagenic potency of
      NDFs in strain TA98 without S9 mix was 2,8- = 2,7-->3-->2-->4-->1-nitrated
      dibenzofuran and 2-NDF and 2,8-dinitrodibenzofuran (DNDF) were more mutagenic
      than 3-NDF and 2,7-DNDF, respectively, in strain TA98NR with S9 mix. The
      mutagenic potency of 2-NDF, 4-NDF, 2,7-DNDF and 2,8-DNDF in strain TA98NR with S9
      mix was stronger than those in strain TA98 without S9 mix and the cytosolic
      fraction of the 3-MC-S9 accounted for more of the activation than the microsomal
      fraction. Studies with electron donors and inhibitors indicated that xanthine
      oxidase and/or NAD(P)H-quinone oxido-reductase (NQOR) participated in the
      activation of NDFs. The mutagenic potency of NDFs in strain TA98NR with S9 mix (3
      MC-S9) was reflected in the induction of NQOR by pretreatment of rats with 3-MC.

PMID- 7521009
TI  - Mutagenesis of yeast MW104-1B strain has identified the uncharacterized PMS6 DNA
      mismatch repair gene locus and additional alleles of existing PMS1, PMS2 and MSH2
      genes.
AB  - The haploid yeast Saccharomyces cerevisiae MW104-1B strain was disomic for
      chromosome III (n + 1) and carried DNA mismatches at three different
      heteroallelic loci; leu2 (leu2-1/leu2-27), thr4 (thr4-1/thr4-16) and his4 (his4
      4/his4-519) (Williamson, 1984). We mutagenized the MW104-1B strain and identified
      seven mutant isolates that display elevated mitotic/meiotic prototrophs due to
      mismatch repair failures at heteroallelic loci. Three mutants (pms1, pms2 and
      pms3) isolated earlier from MW104-1B were shown to correct in vitro constructed
      plasmids with defined DNA mismatches (G/T, A/C, G/G, etc.) poorly (Kramer et al.,
      1989a). Complementation tests were performed by crossing all seven new mutant
      isolates to pms1 and pms2 mutants and assaying for mutant phenotype in the
      diploids. Four mutant isolates failed to complement the two known pms alleles
      (pms1-1 and pms2-1). Two other mutant isolates complemented the pms1-1 and pms2-1
      alleles, but failed to complement each other and were named as the pms5-1 allele
      of an uncharacterized gene (PMS5). One other mutant isolate complemented the pms1
      1, pms2-1 and pms5-1 alleles and was named as the pms6-1 allele of another
      uncharacterized gene (PMS6). Subsequently, the pms5-1 mutant allele was shown to
      be complemented by a plasmid borne yeast MSH2 gene, implying that it is an allele
      of MSH2 (PMS5). The human homologs (hMSH2 and hMLH1) of two yeast DNA mismatch
      repair genes (MSH2 and MLH1) have been cloned recently and shown to be
      responsible for hereditary nonpolypnosis colon cancer (HNPCC) (Fishel et al.,
      1993; Leach et al., 1993; Bronner et al., 1994; Papadopoulos et al., 1994).

PMID- 7521010
TI  - Measurement by 32P-postlabeling of (+/-)anti-benzo[a]pyrene-diolepoxide-N2
      deoxyguanosine adduct persistence in unstimulated human peripheral blood
      lymphocytes.
AB  - In order to study the relative importance of endogenous and environmental factors
      for the individual relation between DNA damage and DNA excision repair, a method
      was developed for measuring quantitatively the persistence of N2-deoxyguanosine
      adducts formed in non-stimulated isolated human peripheral blood lymphocytes
      after in vitro incubation with 0.2 microM (+/-)anti-BPDE, applying 32P
      postlabeling. Total binding of radiolabeled (+/-)anti-BPDE to DNA and its removal
      has been studied previously in human peripheral blood lymphocytes, but the method
      presented here enables the direct investigation of repair of the main (+/-)anti
      BPDE-DNA adduct, which is implicated in benzo[a]pyrene-induced mutagenesis. Using
      this method, it was found that in lymphocytes, obtained from 5 individuals, most
      (+/-)anti-BPDE-N2-dG adducts are removed within the first 24 h after treatment,
      while interindividual differences appear to exist in both adduct formation and
      rate and extent of removal.

PMID- 7521011
TI  - Effect of abasic sites on bacteriophage T7 protein synthesis.
AB  - We have examined protein synthesis directed by bacteriophage T7 which had been
      alkylated with methyl methanesulfonate so as to produce apurinic sites in its DNA
      in vivo. Both repair-proficient and repair-deficient (xth nfo mutant) strains of
      Escherichia coli served as host cells. In repair-proficient cells, all three
      classes of phage proteins were synthesized, although with significant delays. In
      mutant cells, only class I proteins were produced and their synthesis was delayed
      and reduced, demonstrating a perturbation of protein synthesis and providing the
      first in vivo indication that transcription is inhibited by abasic sites.
      However, the proposed effects of abasic sites on transcription appear to be
      weaker than those on replication.

PMID- 7521012
TI  - Cytogenetic effects on human lymphocytes of a mixture of fifteen pesticides
      commonly used in Italy.
AB  - Lymphocytes obtained from 5 healthy donors were incubated with a mixture of 15
      pesticides commonly found in foods of central Italy (dithiocarbamates (20.7%),
      benomyl (19.6%), thiabendazole (14.9%), diphenylamine (14.4%), chlorthalonil
      (13.1%), procymidone (8.0%), methidathion (2.3%), chlorpyrifos-ethyl (2%),
      fenarimol (1.9%), parathion-methyl (1%), chlorpropham, parathion, vinchlozolin,
      chlorfenvinphos and pirimiphos-ethyl (< 1%)). The percent of each pesticide in
      the mixture was proportional to its average concentration in foods. Incubated
      with the lymphocytes at a concentration of 1-20 micrograms/ml the pesticide
      mixture did not induce significant variations in the number of hypodiploid,
      hyperdiploid and polyploid cells or in the number of chromosome and chromatid
      aberrations. On the contrary, we observed a dose-dependent increase in the number
      of nonsynchronous centromeric separations which reached the level of 37.9% at 20
      micrograms/ml of pesticide mixture in the incubation medium. This effect was not
      observed when benomyl was excluded from the mixture. These data show that the
      removal of benomyl could decrease the toxicity of pesticide residues present in
      human food.

PMID- 7521013
TI  - Mutagenic evaluation of primaquine, pentaquine and pamaquine in the
      Salmonella/mammalian microsome assay.
AB  - The 8-aminoquinolines, primaquine, pentaquine and pamaquine, were investigated
      for mutagenic activity in Salmonella typhimurium strains TA100, TA98, TA97 and
      TA102 in the rat liver microsomal activation system. Primaquine and pentaquine
      induced mutations in TA97 in the presence and absence of S9 mix. Pamaquine was
      mutagenic to TA98 only in the absence of S9 mix.

PMID- 7521014
TI  - In vitro evolution of new ribozymes with polynucleotide kinase activity.
AB  - We have isolated a large number of polynucleotide kinase ribozymes from a pool of
      RNA molecules consisting of an ATP-binding domain flanked by regions of random
      sequence. Different classes of kinases catalyse the transfer of the gamma
      thiophosphate of ATP-gamma S to the 5'-hydroxyl or to internal 2'-hydroxyls. An
      engineered version of one class is able to catalyse the transfer of thiophosphate
      from ATP-gamma S to the 5'-hydroxyl of an exogenous oligoribonucleotide substrate
      with multiple turnover, thus acting as a true enzyme.

PMID- 7521015
TI  - Ion channels. Enter the 'swinging gate'.

PMID- 7521017
TI  - Whipple's disease. The Duke connection.

PMID- 7521016
TI  - Identification of a translocated protein segment in a voltage-dependent channel.
AB  - Voltage-gated channels undergo a conformational change in response to changes in
      transmembrane voltage. Here we use site-directed biotinylation to create
      conformation-sensitive sites on colicin Ia, a bacteriocidal protein that forms a
      voltage-sensitive membrane channel, which can be monitored by
      electrophysiological methods. We investigated a model of gating developed for the
      partly homologous colicin E1 that is based on the insertion of regions of the
      protein into the membrane in response to cis-positive voltages. Site-directed
      cysteine mutagenesis, followed by chemical modification, was used to attach a
      biotin molecule covalently to a series of unique sites on colicin Ia. The
      modified protein was incorporated into planar lipid membranes, where the
      introduced biotin moiety served as a site to bind the water-soluble protein
      streptavidin, added to one side of the membrane or the other. Our results show
      that colicin gating is associated with the translocation across the membrane of a
      segment of the protein of at least 31 amino acids.

PMID- 7521019
TI  - Low density lipoprotein uptake by macrophages in multiple sclerosis plaques:
      implications for pathogenesis.
AB  - Low density lipoprotein (LDL), the major carrier of plasma cholesterol, may enter
      the parenchyma of early multiple sclerosis (MS) lesions as a result of blood
      brain barrier damage. We have used antibodies against LDL and epitopes found in
      LDL oxidized by two peroxidative end-products, malondialdehyde (MDA) and 4
      hydroxynonenal (4-HNE), to immunocytochemically stain MS plaques at different
      stages of pathology. Native LDL, epitopes of MDA-LDL, peptides of myelin basic
      protein and neutral lipid oil red O (ORO) staining were found to be co-localized
      within foamy macrophages in early and actively demyelinating MS plaques. Thus
      cholesterol esters, which are seen as Maltese crosses under polarized light in a
      proportion of foamy macrophages, appear to be derived from both LDL and myelin.
      ORO-negative astrocytes were strongly stained with the antibodies against 4-HNE
      LDL and MDA-LDL, suggesting uptake of oxidatively modified protein products
      alone. Our findings suggest that a large proportion of the plasma LDL which
      enters the parenchyma of MS plaques is oxidatively modified in the lesion. Lipid
      peroxidation and oxidized LDL uptake by activated microglia and infiltrating
      macrophages in the early stages of MS plaque development may play important roles
      in demyelination.

PMID- 7521018
TI  - [Recognition of familiar handwriting after left hemisphere and right hemisphere
      brain damage].
AB  - The recognition of handwriting is a specific achievement of the brain which need
      not be connected to understanding the written text itself. The goal of this study
      was to determine how this ability is impaired in patients with left- or right
      sided lesions. Seventeen aphasic patients with lesions in the left hemisphere, 16
      patients with lesions in the right hemisphere, and 15 normal controls (without
      CNS illness or damage) were investigated. They were asked to recognize the
      handwriting of a person well-known to them among a sample of ten different
      handwritten texts. The aphasic patients were able to recognize the handwriting of
      the familiar person either immediately or after some delay in 96%, the non
      aphasic patients in only 44%, and the healthy controls in 100% of the cases.
      Results indicate that the recognition of handwriting represents a specific
      achievement which is independent of other verbal and lexical tasks. It is a task
      which involves the recognition of figural, geometric spatial patterns and, thus,
      an achievement of the non-dominant hemisphere.

PMID- 7521020
TI  - Amyloid precursor protein (APP) as a microglial acute phase protein.

PMID- 7521021
TI  - Role of microglia in autoimmune encephalomyelitis.

PMID- 7521023
TI  - An oriented framework of neuronal processes in the ventral lateral geniculate
      nucleus of the rat demonstrated by NADPH diaphorase histochemistry and GABA
      immunocytochemistry.
AB  - This study investigated the morphology and quantitative distribution of neurons
      containing NADPH diaphorase activity in the ventral lateral geniculate nucleus of
      the rat. The pattern of diaphorase staining revealed a strongly reactive lateral
      subdivision and a weakly staining medial subdivision. A characteristic feature of
      the diaphorase staining in the lateral part was its "stripe-like" appearance.
      These "diaphorase stripes" resulted from regions of strong somatic and neuropil
      diaphorase activity lying between unstained fibre bundles coursing dorsoventrally
      through the nucleus. Two distinct populations of diaphorase reactive cell types
      were present--class A and class B neurons. The ratio of class A to class B
      diaphorase neurons was approximately 14:1 (A:B). Diaphorase reactive neurons made
      up 73% of the total neuron population in the lateral subdivision, and 31% in the
      medial subdivision. A third population of cells was found exclusively in the
      optic tract--class C neurons. Quantitative analyses in the coronal and sagittal
      planes indicated that the principal processes of both class A and class B neurons
      were oriented preferentially--either parallel with, or perpendicular to the
      outlying optic tract. Diaphorase enzyme histochemistry in combination with GABA
      immunocytochemistry demonstrated the co-localization of GABA immunoreactivity in
      the majority of class B neurons, whereas class A and class C neurons were GABA
      immunonegative. Furthermore a large population of GABA-immunoreactive neurons was
      present that were not stained for diaphorase activity. From this and previous
      studies, it can be concluded that a high proportion of the diaphorase reaction
      class A neurons are geniculotectal projection cells, while diaphorase reaction
      class B neurons represent a numerically small subpopulation of "local-circuit"
      inhibitory neurons. Since diaphorase activity co-localizes with nitric oxide
      synthase, the results indicate the likely involvement of nitric oxide in the
      neuronal operations of both subpopulations of geniculotectal projection neurons
      and "local-circuit" GABAergic neurons in the rat's ventral lateral geniculate
      nucleus.

PMID- 7521022
TI  - Activity at phencyclidine and mu opioid sites mediates the hyperalgesic and
      antinociceptive properties of the N-terminus of substance P in a model of
      visceral pain.
AB  - Substance P, a putative neurotransmitter or neuromodulator of nociception or pain
      in the spinal cord, exhibits both antinociceptive and hyperalgesic properties.
      Investigators have shown that the N-terminal metabolite of substance P, substance
      P(1-7), produces naloxone-reversible antinociception when given supraspinally and
      systemically in mice and hyperalgesia when injected intrathecally in rats. The
      goal of our investigation was to identify the receptors mediating these actions
      of substance P(1-7) at the initial site of release of substance P, i.e. in the
      spinal cord. Thirty minutes after intrathecal injection, substance P(1-7)
      produced naloxone-reversible antinociception in a dose-dependent manner in the
      abdominal stretch assay. When administered with naloxone, substance P(1-7)
      produced hyperalgesia 5 and 10 min after injection, which was inhibited by
      dizocilpine (MK-801), a phencyclidine ligand and non-competitive antagonist of N
      methyl-D-aspartate. Antinociception was inhibited by the mu-selective opioid
      antagonist beta-funaltrexamine, but not by the mu 1-selective opioid antagonist
      naloxonazine or the delta-selective antagonist naltrindole, indicating a mu 2
      opioid receptor-mediated effect. These findings suggest that the N-terminal
      portion of substance P may modulate nociception or pain, as demonstrated in the
      acetic acid abdominal stretch (writhing) assay, via activation of two different
      receptor systems. Substance P(1-7)-induced hyperalgesia is mediated by a
      phencyclidine-sensitive mechanism and antinociception involves activity at mu
      opioid, most likely mu 2, receptors.

PMID- 7521024
TI  - Vanadate stimulates differentiation and neurite outgrowth in rat pheochromocytoma
      PC12 cells and neurite extension in human neuroblastoma SH-SY5Y cells.
AB  - We show here that a protein tyrosine phosphatase inhibitor, sodium orthovanadate,
      induces rat pheochromocytoma cells to express neurites, a prominent morphological
      marker of neuronal phenotype. Vanadate-induced differentiation and neurite
      outgrowth in pheochromocytoma cells was not as extensive as that induced by the
      positive control employed, nerve growth factor. However, neurite outgrowth
      responses were comparable between nerve growth factor-treated pheochromocytoma
      cells and cells primed and then restimulated with vanadate. In the human
      neuroblastoma cell line, SH-SY5Y, a single exposure to vanadate induced neurite
      extension in this cell line equal to that initiated by nerve growth factor. In
      both cell lines vanadate treatment resulted in tyrosine phosphorylation of
      several high-molecular-weight proteins and using anti-phosphotyrosine antibodies,
      intense fluorescence was observed in the cell body and neurites of
      pheochromocytoma cells exposed to vanadate. Vanadate mediated differentiation and
      neurite outgrowth in pheochromocytoma cells could be ablated by the tyrosine
      kinase inhibitor erbastatin, whereas nerve growth factor-induced neurite
      outgrowth was only partially inhibited. In SH-SY5Y cells, erbstatin mediated
      partial inhibition of both vanadate and nerve growth factor-induced neurite
      elongation with similar kinetics. In contrast, K252b, a trk tyrosine kinase
      inhibitor, exhibited only a 30% reduction of neurite outgrowth in vanadate
      treated pheochromocytoma cells but an 80% reduction in nerve growth factor
      treated cells. In SH-SY5Y cells, K252a did not have a statistically significant
      effect on neurite elongation induced by vanadate in contrast to a 60% reduction
      in nerve growth factor-treated cells. The membrane impermeable analogue K252b,
      had no effect on neurite elongation induced with either vanadate or nerve growth
      factor in these cells. The effects of vanadate were not mimicked by ouabain (0.1
      50 microM) indicating that vanadate does not induce differentiation and/or
      neurite extension by inhibiting ion channel Na,K-ATPase, which is one of its
      other well-characterised inhibitory activities. Evidence for the selective action
      of vanadate on some but not all neuronal cell lines comes from the fact that it
      did not induce neurite extension in the human neuroblastoma cell line SK-N-MC.
      These data imply that vanadate-induced neurite outgrowth responses in
      pheochromocytoma and SH-SY5Y cells can be induced by the inhibition of tyrosine
      phosphatases and appears not to simply mimic nerve growth factor signals. The
      target(s) of vanadate action in the two cell lines are currently being sought.

PMID- 7521025
TI  - Structural and molecular heterogeneity of astrocytes and oligodendrocytes in the
      gerbil lateral superior olive.
AB  - The goal of this study was to determine the distribution and diversity of
      astrocytes and oligodendrocytes within the lateral superior olive of the gerbil.
      We used morphometric analyses and several immunocytochemical markers to assess
      differences in glial cell composition between the lateral (low-frequency
      projection) and the medial (high-frequency projection) limb of the lateral
      superior olive. Cell counts from Toluidine-stained semithin sections revealed a
      similar density of total astrocytes in both the lateral and the medial limbs.
      However, based on cytologic features, there was a prevalence of fibrous-like
      astrocytes in the lateral limb and protoplasmic-like astrocytes in the medial
      limb. In a similar manner, glial fibrillary acidic protein staining of astrocytes
      was intense in the lateral limb, but was largely restricted to the nucleus
      borders in the medial limb of the lateral superior olive. While glial fibrillary
      acidic protein was largely restricted to astrocytic processes, glutamine
      synthetase and S100 protein staining occurred, for the most part, in glial cell
      bodies. The density of glutamine synthetase positive cell bodies was homogeneous
      between the two limbs, while the density of S100-positive somata was
      significantly greater in the lateral limb. Cell counts obtained from semithin
      sections demonstrated a greater density of oligodendrocytes in the lateral limb
      than in the medial limb of the lateral superior olive. In a similar manner, there
      was a 40% greater density of carbonic anhydrase-positive somata in the lateral
      limb compared to the medial limb. Transferrin immunostaining was restricted to
      oligodendrocytes, but the density of labeled somata was identical in the lateral
      and medial limbs. 2',3'-Cyclic nucleotide 3'-phosphodiesterase and myelin
      associated glycoprotein were also localized to the somata of oligodendrocytes,
      labeling both perisomatic and interfascicular cells. At the ultrastructural
      level, specialized contacts were found between pairs or clusters of
      oligodendrocytes. These results suggest that more than one type of astrocyte and
      oligodendrocyte is present within the gerbil lateral superior olive. Furthermore,
      glial cells were unevenly distributed, such that a greater density of
      oligodendrocytes and fibrous-like astrocytes were found in the low-frequency
      projection region. This heterogeneity is well correlated with known differences
      in the neuronal morphology within the lateral superior olive.

PMID- 7521026
TI  - Extent of bilateral collateralization among pontomesencephalic tegmental
      afferents to dorsal lateral geniculate nuclei of pigmented and albino rats.
AB  - In adult pigmented and albino rats, small amounts of different fluorescent dyes
      (Fast Blue and Fluoro-Gold) were pressure-injected into the dorsal lateral
      geniculate nuclei, each nucleus (right or left) being injected with one dye only.
      After postinjection survival of three days, the distribution of neurons
      retrogradely labelled by each dye was analysed. Consistent with previous studies,
      in each strain each dye labelled a large number of neurons in the several
      ipsilateral visuotopically or retinotopically organized structures--visual
      cortices, retino-recipient layers of the superior colliculi and the pretectal
      nuclei. A substantial number of retrogradely labelled neurons was also found in
      the contralateral parabigeminal nucleus. A few retrogradely labelled neurons were
      found in the ipsilateral and (to a lesser extent) contralateral dorsolateral
      divisions of the periaqueductal gray matter, as well as in the ipsilateral
      parabigeminal nucleus and the caudal part of the lateral hypothalamus. However,
      in all the above structures there was a paucity of cells retrogradely labelled
      with both dyes (double-labelled cells). By contrast, in each strain, several
      "modulatory" nuclei (containing cholinergic and aminergic cells) of the
      pontomesencephalic tegmentum--dorsal raphe, pedunculopontine tegmental nucleus,
      parabrachial nucleus, laterodorsal tegmental nucleus and locus coeruleus-
      contained significant numbers of cells projecting to both ipsilateral and
      contralateral dorsal lateral geniculate nuclei. In each nucleus, ipsilaterally
      and contralaterally projecting cells constituted, respectively, about 65-70% and
      about 30-35% of retrogradely labelled cells. About 25% of the contralaterally
      projecting cells (i.e. about 5-10% of all retrogradely labelled tegmental
      neurons) were double-labelled with both dyes. Double-labelled cells were
      intermingled with single-labelled cells projecting ipsilaterally or
      contralaterally. The proportions of the ipsilaterally, contralaterally and
      bilaterally projecting neurons in the modulatory components of the
      pontomesencephalic tegmentum were virtually identical in pigmented and albino
      strains. It appears that in both strains the visuotopically organized structures
      convey to the dorsal lateral geniculate nuclei information related mainly to the
      contralateral visual field. The projections from these structures might play an
      important role in regulating transmission of visual information in the
      retinotopically distinct parts of each dorsal lateral geniculate nucleus. By
      contrast, the projections from the modulatory nuclei of the pontomesencephalic
      tegmentum are likely to contribute to the functional synchronization of both
      dorsal lateral geniculate nuclei during the sleep-wakefulness cycle and saccadic
      eye movements.

PMID- 7521028
TI  - Intranasal calcitonin therapy in Sudeck's atrophy.

PMID- 7521027
TI  - Role of proteinase/antiproteinase inhibitor disequilibrium in the
      bioincompatibility induced by artificial surfaces.
AB  - As one aspect of bioincompatibility, the importance of activation of proteolytic
      systems as a result of an imbalance between protease and antiprotease activity
      has been increasingly recognized. This principle is illustrated by selected
      studies in our laboratory. These concern (i) generation of kinins on membranes
      with negative surface charge, (ii) activation of the complement system as a
      function of binding to the membrane of the regulatory protein H, (iii) generation
      of thrombin-antithrombin complexes (TAT), and (iv) generation of
      plasmin/antiplasmin complexes with an interesting discrepancy between in vivo and
      in vitro.

PMID- 7521030
TI  - A cultural study on corneal explants and clinic assessment of the effectiveness
      of treating corneal ulcers induced by alkal test with topic aprotinin and
      fibronectin.
AB  - The A.A. studied the effectiveness of colliriums containing fibronectins
      aprotinin, and fibronectin associated with aprotinin compared to a placebo using
      12 rabbits in which a deep corneal ulcer was induced by alkal. The results showed
      the same effectiveness of the three collyrium versus the placebo there was
      clinical recovery in all cases and restoration of corneal trasparency for 13 out
      of 15 treated eyes. Cellular cultures obtained from primary explants of treated
      corneal cells, compared with non treated groups, gave the same outcome of the
      clinical's ones.

PMID- 7521029
TI  - Genetic control of the antibody repertoire against excretory/secretory products
      and acetylcholinesterases of Dictyocaulus viviparus.
AB  - Outbred Dunkin-Hartley and inbred strain 2 and strain 13 guinea pigs were
      immunized with Dictyocaulus viviparus adult ES products prior to challenge with
      third stage larvae. Antibody responses of the three strains to adult ES products
      and the acetylcholinesterase (AChE) isoforms which they contain were examined.
      Using immunoprecipitation and ELISA, it was observed that responses in the three
      strains to adult ES products were distinct: considerable heterogeneity in the
      antibody repertoire was observed between outbred Dunkin-Hartley animals, with
      only slight variation occurring amongst the inbred individuals. Responses to the
      AChE isoforms were heterogeneous amongst individual outbred guinea pigs but were
      more consistent in inbred strain 2 and 13 animals in which strain-specific
      patterns of recognition were observed. Previous studies with nematode infections
      have indicated a role for the major histocompatibility complex in determining the
      nature and level of the immune response. As the inbred strains bear different
      alleles at the Class II region but are identical at the Class I region, the
      differences observed are likely to be due to genes mapping to the Class II locus.
      This is therefore the first report of genetic restriction of the antibody
      repertoire to secreted AChEs of a parasitic nematode.

PMID- 7521033
TI  - Endpoints and trials: a matter of life and death.

PMID- 7521032
TI  - Insulin reverses ammonia-induced anorexia and experimental cancer anorexia.
AB  - Previous experiments suggest that experimental cancer-induced anorexia is
      associated with hyperammonemia and that daily injections of insulin may attenuate
      the anorexia for several days. In the present study, we determined whether
      similar daily insulin treatments would correct anorexia induced by the infusion
      of ammonium salts and compared this feeding response with that of insulin-treated
      tumor-bearing (TB) rats. Daily treatment of control and anorectic TB rats with
      systemically administered insulin for six days increased feeding in all control
      rats and 40% of the TB rats. All insulin-treated groups exhibited equal degrees
      of hypoglycemia irrespective of anorexia. Basal concentrations of lactate and
      glucagon were elevated in saline-treated TB rats. Plasma lactate levels were
      normalized by insulin treatment, whereas glucagon was normalized only in the TB
      rats that fed to insulin and increased further in TB rats that did not feed to
      insulin. Elevated hypothalamic tyrosine was reduced in insulin-treated TB rats
      that ate, and 5-hydroxy-indoleacetic acid was increased further when the rats did
      not eat. Insulin also blocked anorexia resulting from the intravenous infusion of
      ammonium salts. Hypothalamic concentrations of tyrosine and tryptophan were
      increased by the ammonia infusion and reduced significantly in insulin-treated
      infused rats. These results indicate that insulin treatment can reverse
      experimental cancer-induced anorexia and hyperammonemia-induced anorexia.
      Neurochemical changes associated with these treatments are also similar, but not
      identical.

PMID- 7521031
TI  - Expression of a renal Na(+)-nucleoside cotransport system (N2) in Xenopus laevis
      oocytes.
AB  - Xenopus laevis oocytes have been used for the expression of a renal, pyrimidine
      selective, Na(+)-nucleoside cotransporter (N2). As compared to its uptake in
      water-injected oocytes, Na(+)-dependent thymidine uptake was enhanced in a time-
      and dose-dependent manner in oocytes injected with rat renal cortex total
      poly(A)+ RNA. An increased uptake was also observed after injection of size
      fractionated rat renal cortex poly(A)+ RNA (2-3 kb). Consistent with the
      selectivity of the N2 nucleoside transporter, cytidine significantly inhibited
      Na(+)-dependent thymidine uptake in oocytes injected with total poly(A)+ RNA
      whereas guanosine and formycin B did not. Na(+)-dependent thymidine uptake was
      also enhanced in oocytes injected with size fractionated human renal cortex
      poly(A)+ RNA (2-3 kb). The above data demonstrate functional expression of renal
      cortex, Na(+)-nucleoside cotransporters in Xenopus laevis oocytes.

PMID- 7521034
TI  - Ventricular arrhythmia factors in mitral valve prolapse.
AB  - To assess the prevalence of ventricular arrhythmias and late potentials (LPs) in
      mitral valve prolapse (MVP) and to identify clinical, ECG, and echocardiographic
      markers of spontaneous ventricular arrhythmias, we studied 58 consecutive
      patients (mean age 46.6 +/- 17.8 years; 29 males, 29 females) with MVP diagnosed
      by echocardiography. Patients underwent ambulatory ECG recording (n = 58),
      exercise stress test (n = 56), signal-averaged ECG (n = 58), and programmed
      ventricular stimulation (n = 52). Ten patients (17.2%) had spontaneous
      nonsustained ventricular tachycardia (NSVT), 26 patients (44.8%) had premature
      ventricular contractions (PVCs), Lown grade > or = 3 during 24-hour ECG, and 19
      had Lown grade > or = 3 PVCs during exercise stress test; 13 patients had LPs
      (22.4%). We provoked sustained VT in one case and NSVT in ten cases. Patients
      with complex ventricular arrhythmias during 24-hour ECG and exercise stress test
      were older and more often had mitral regurgitation. There was a statistical
      correlation between the presence of LPs and spontaneous VT (46.1% vs 8.9%; P <
      0.005) and induced ventricular arrhythmias (50% vs 12.8%; P < 0.005). No
      correlation was found between spontaneous ventricular arrhythmias and thickness
      or posterior displacement of the mitral valve. In conclusion, complex ventricular
      arrhythmia (especially VT) and LPs are frequent in MVP. Patient age and mitral
      regurgitation seem to be determinant factors of complex ventricular arrhythmias
      in MVP. On signal-averaged ECG, absence of LPs seems to be a good additional
      marker to identify MVP patients without spontaneous VT. On the other hand,
      programmed ventricular stimulation does not appear valuable in determining a MVP
      subgroup with a high risk of ventricular arrhythmias.

PMID- 7521035
TI  - Systolic arterial pressure recovery after ventricular fibrillation/flutter in
      humans.
AB  - Although the elective induction of cardiac arrest for implantable defibrillator
      insertion under general anesthesia is widely used, the hemodynamics of recovery
      of arterial blood pressure after cardiac arrest is not well-defined. Accordingly,
      the time course of recovery of systolic arterial pressure was studied in seven
      patients during the repetitive induction of ventricular fibrillation (n = 6) or
      ventricular flutter (n = 1). The mean number of episodes of cardiac arrest was 7
      +/- 2, and the mean drop in systolic pressure was 84 +/- 16 mmHg. The mean
      recovery time for systolic pressure was 10 +/- 6 seconds, the average systolic
      pressure recovery rate was 13 +/- 14 mmHg/sec, and the mean percent systolic
      pressure recovery was 94% +/- 9%. A negative logarithmic relation was found to
      exist between the rate of systolic arterial pressure recovery and the duration of
      ventricular fibrillation or flutter with a correlation coefficient of 0.68 to
      0.97 (P < 0.05) in five of the seven patients. A linear relation between the time
      for systolic pressure recovery and duration of asystole was also defined. These
      results are consistent with the view that prolongation of ventricular
      fibrillation or flutter increases the duration of arterial pressure recovery
      through a negative effect on left ventricular contractility. Increased
      understanding of these relations may lead to increased safety of implantable
      defibrillator insertion.

PMID- 7521037
TI  - Atrial late potentials in patients with paroxysmal atrial fibrillation detected
      using a high gain, signal-averaged esophageal lead.
AB  - High gain, signal-averaged ECGs using conventional surface lead technique and a
      transesophageal lead technique were performed in 45 idiopathic paroxysmal atrial
      fibrillation patients and in 33 normal controls. Both techniques showed increased
      P wave duration in patients compared with the controls (P < 0.001), but higher P
      wave amplitudes were obtained using the transesophageal technique compared with
      surface leads (patients: 169.8 +/- 81.7 microV vs 15.8 +/- 7.3 microV; P <
      0.0005; controls: 163.5 +/- 22.1 microV vs 18.5 +/- 5.2 microV; P < 0.0005). The
      signal-averaged transesophageal lead, but not the surface recordings, identified
      the presence of atrial late potentials evidenced by lower root mean square
      voltages in the terminal portion of the P wave: in last 10 seconds, 4.4 +/- 1.3
      microV versus 8.5 +/- 3.0 microV; P < 0.001; in last 20 seconds, 7.0 +/- 2.3
      microV versus 16.0 +/- 7.9 microV; P < 0.001; in last 30 seconds, 12.5 +/- 5.3
      microV versus 23.8 +/- 12.8 microV; P < 0.001, in patients with respect to
      controls. The criterion P wave duration > or = 110 msec had 85% sensitivity, 100%
      specificity, and 100% positive predictive value in identifying the patients; the
      combined criteria P wave duration > or = 110 msec and root mean square for the
      last 10 msec < or = 6.5 showed 80% sensitivity, 100% specificity, and 100%
      predictive value. The signal-averaged transesophageal lead produces a higher
      amplitude signal, which reveals fractionation of atrial activation in atrial
      fibrillation and allows identification of individuals predisposed to this
      arrhythmia.

PMID- 7521036
TI  - Influence of filtering techniques on the time-domain analysis, diagnosis, and
      clinical use of signal-averaged electrocardiogram.
AB  - In order to investigate the effect of different filtering techniques on the time
      domain analysis of signal-averaged electrocardiogram (SAECG), recordings of 1,192
      subjects were analyzed using Butterworth and Del Mar filters, both set at 40-250
      Hz high and low pass frequencies. The recordings were taken from six clinically
      defined groups: (a) survivors of acute myocardial infarction (n = 553); (b)
      patients with sustained symptomatic postinfarction ventricular tachycardia (n =
      89); (c) patients with hyperthropic cardiomyopathy (n = 219); (d) patients with
      dilated cardiomyopathy (n = 76); (e) direct relatives of patients with dilated
      cardiomyopathy (n = 170); and (f) normal healthy volunteers (n = 85). The study
      investigated differences between the SAECG results reported with both filters in
      three individual aspects: (1) numerical values of individual time-domain SAECG
      variables; (2) differences in SAECG findings of patients with postinfarction
      ventricular tachycardia and pair matched patients with uncomplicated follow-up
      after acute infarction; and (3) the power of SAECG findings to predict high risk
      of arrhythmic complication (sudden death and/or sustained ventricular
      tachycardia) among survivors of acute myocardial infarction. Compared with the
      Butterworth filter, the Del Mar filter led to a systematic difference of +8% in
      total QRS duration, was equally powerful in distinguishing between the pair
      matched patients with and without postinfarction ventricular tachycardia, and was
      statistically significantly more powerful in identifying those survivors of acute
      infarction who were at high risk of arrhythmic complications. The study concludes
      that the use of different filters may produce discordant results of SAECG
      analysis. Normal and abnormal values for various types of SAECG recording and
      analysis have to be established individually for different equipment and
      different software settings. These optimal cut-offs of SAECG variables should
      also take into account the clinical characteristics of patient groups.

PMID- 7521038
TI  - Intra-His bundle block corresponds with interruption of the branching portion of
      the His bundle.
AB  - We compared His-bundle electrograms with pathological findings of the
      atrioventricular conduction system in four patients with complete
      atrioventricular intra-His block with narrow QRS complexes on ECG. Split His
      electrograms were recorded at the time of electrophysiological study. The
      patients died from noncardiac causes at 10 days, 1 year, 4 years, and 9 years,
      respectively, after the pacemaker implantation. Serial sections through the
      atrioventricular conduction system revealed strictly localized more than 50%
      reduction of conducting cells replaced by fibrosis at the branching portion of
      His bundle. The proximal portions of the bundle branches also exhibited decrease
      of the conducting cells showing a rough positive relation with the patient's age.
      Therefore, we considered that the H1 spikes seen on His-bundle electrograms
      originated from the penetrating portion of His, which was virtually intact in our
      cases, and that the H2 spikes originated from the right side of the distal
      branching portion of His.

PMID- 7521039
TI  - A new steroid-eluting screw-in electrode.
AB  - A new lead design was tested that combined a small microporous steroid-eluting
      electrode with an insulated, exposed helix for active fixation. This lead (model
      5078, Medtronic, Inc., group I, n = 10) was compared to a conventional model
      (model Y 60 BP, Biotronik) with a larger surface of polished platinum-iridium,
      equipped with a fixed, noninsulated screw but without steroid elution (group II,
      n = 10). The two lead models were studied in the atrial position of dual chamber
      pacing systems, which all had a tined ventricular lead (model 5024, Medtronic,
      Inc.), with essentially the same steroid-eluting tip as the new active fixation
      lead design. Sensing and pacing data were recorded acutely and during 1 year of
      follow-up, via the telemetry of a Relay pulse generator (Intermedics, Inc.).
      Intraoperatively, unfiltered atrial electrogram amplitudes did not differ between
      groups (group I: 7.12 +/- 2.56 mV vs group II: 6.42 +/- 1.87 mV; P > 0.05), nor
      did sensing thresholds 1 year after implantation (group I: 5.33 +/- 1.70 mV vs
      group II: 4.26 +/- 1.40 mV; P > 0.05). Atrial pacing thresholds as measured
      during surgery at a pulse width of 0.5 msec were lower in group I (0.49 +/- 0.15
      V) than in group II (0.68 +/- 0.19 V; P < 0.05). From day 5 through day 360 of
      follow-up, the difference in atrial pacing thresholds was highly significant (P <
      0.01), with a smaller peaking of early thresholds and a much lower scattering of
      data for the steroid screw-in leads than for controls.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7521040
TI  - Predictors of successful radiofrequency ablation of extranodal slow pathways.
AB  - Catheter positioning for radiofrequency ablation of extranodal slow pathways is
      often guided by local electrogram recordings. To determine the predictors of
      successful ablation sites, we reviewed data from 32 successful and 104
      unsuccessful sites. Univariate predictors of a successful site included the
      occurrence of junctional rhythm during ablation (P < 0.001), shorter time to
      onset of junctional rhythm (P = 0.05), the presence of a discrete slow pathway
      potential (P < 0.001), a smaller ratio of the amplitude of the atrial:ventricular
      electrogram (P = 0.04), later timing (P = 0.001) and longer duration (P < 0.001)
      of the atrial slow pathway electrogram, and the duration of (P < 0.001), and
      maximal voltage used during ablation (P < 0.001). By multivariate analysis
      junctional rhythm (P < 0.001), a discrete slow pathway potential (P = 0.003), a
      longer duration of the atrial slow pathway electrogram (P = 0.01) and the
      duration of ablation (P = 0.02) were predictors of success. Because ablations at
      unsuccessful sites were often aborted at 10-30 seconds, a separate analysis was
      performed using only the 41 unsuccessful sites where the duration of ablation was
      > or = 30 seconds. The results were nearly identical. Thus, the occurrence of
      junctional rhythm during ablation and the morphology and duration of the atrial
      slow pathway electrogram may serve as guides for slow pathway ablation site
      selection.

PMID- 7521041
TI  - Variability of left atrial bloodflow predicts intolerance of ventricular demand
      pacing and may cause pacemaker syndrome.
AB  - Variability of left and right atrial and left ventricular bloodflow was studied
      using transthoracic and transesophageal Doppler echocardiography and related to
      pacemaker mode preference during everyday activity. Bloodflow variability was
      less at all sites during dual chamber pacing compared to single chamber pacing.
      However, in patients suffering from pacemaker syndrome and who prefer DDDR
      pacing, significantly increased variability of left atrial antegrade (but not
      retrograde) bloodflow during VVIR pacing compared to DDDR pacing was noted, which
      was not evident in patients tolerating VVIR mode pacing. This effect was not
      detected at any other site and suggests that adverse left atrial hemodynamics may
      result in intolerance to VVI/R mode pacing and might cause pacemaker syndrome.

PMID- 7521042
TI  - Fallback responses of dual chamber (DDD and DDDR) pacemakers: a proposed
      classification.

PMID- 7521044
TI  - The British National Health Service.

PMID- 7521043
TI  - Complexity diagnostics in cardiology: fundamental considerations.

PMID- 7521045
TI  - Radiofrequency catheter ablation of the atrioventricular junction by a
      supravalvular noncoronary aortic cusp approach.
AB  - Radiofrequency catheter ablation of the atrioventricular junction is usually
      achieved from either the right or left atrioventricular junction. We describe a
      new approach in which the atrioventricular junction was successfully ablated from
      the supravalvular region of the noncoronary cusp of the aortic valve in an
      unusual patient in whom conventional approaches were unsuccessful.

PMID- 7521048
TI  - Mechanical factors play a significant role in inducing and terminating
      supraventricular and ventricular arrhythmias.

PMID- 7521047
TI  - A report using a hybrid ICD system: the need for compatibility among implanted
      defibrillator components.
AB  - The successful implantation of an ICD system with hardware from three different
      manufacturers is described. This case exemplifies the need for compatibility of
      components among different manufacturers. This is most relevant at a time when
      rapidly changing technology and hardware availability may require a mixing, by
      informed practitioners, of ICD system components. The parallel to the development
      of the uniform IS-1 standard for bradycardia devices is made.

PMID- 7521046
TI  - Nonreentrant supraventricular tachycardia due to simultaneous conduction over
      fast and slow AV node pathways: successful treatment with radiofrequency
      ablation.
AB  - A 55-year-old woman with frequent problematic supraventricular tachycardia is
      presented. The tachycardia was irregular with predominantly normal QRS morphology
      and was refractory to multiple antiarrhythmic drugs. At electrophysiology study,
      the tachycardia was inducible with atrial or ventricular extrastimuli and dual
      pathways were observed. In contrast to the situation usually seen with dual
      atrioventricular node physiology, the slow pathway had a longer effective
      refractory period than the fast pathway and reentrant tachycardia was not
      induced. Simultaneous conduction over the fast and slow pathways during sinus
      rhythm was shown to be the mechanism for clinical tachycardia. The tachycardia
      was successfully treated using radiofrequency ablation of the slow pathway.

PMID- 7521049
TI  - [A case of Whipple's disease].
AB  - We present 66 year old man with symptoms of malabsorption syndrome. The correct
      diagnosis of Whipple's disease was made difficult by the radiological picture of
      the jejunum tumor with subocclusion. It was the cause of the diagnosis of
      carcinoid tumor of the small intestine: the laparotomy was performed. The
      histological picture was typical for Whipple's disease. The skin changes seen in
      our patient were similar like in carcinoid syndrome, pellagra and Whipple's
      disease.

PMID- 7521050
TI  - Effects of mutations at the W locus (c-kit) on inner ear pigmentation and
      function in the mouse.
AB  - The W locus encodes a tyrosine kinase receptor, c-kit, which affects survival of
      melanoblasts from the neural crest. The primary cochlear defect in Viable
      Dominant Spotting (Wv/Wv) mutants is a lack of melanocytes within the stria
      vascularis (SV) associated with an endocochlear potential (EP) close to zero and
      hearing impairment. In this study, we compare inner ear pigmentation with
      cochlear potentials in three other W alleles (Wx, Wsh, and W41) and reveal an
      unequivocal correlation between presence of strial melanocytes and presence of an
      EP. Asymmetry was common, and 8.3% of Wsh/Wx, 25% of Wsh/Wsh, 60% of W41/Wx, and
      69.2% of W41/W41 ears had a pigmented stria and an EP, while the remainder had no
      strial melanocytes and no EP. In those mutants that partially escaped the effects
      of the mutation, strial melanocytes rarely extended the entire length of the
      stria, but were confined to the middle and/or basal turns of the cochlea. The
      extent of strial pigmentation was unrelated to the EP value, which was measured
      from the basal turn only. Compound action potential (CAP) responses recorded from
      ears with an EP were variable and they showed greatly raised thresholds or were
      absent in all ears where the EP was close to zero. In controls, melanocytes in
      the vestibular part of the ear were found in the utricle, crus commune, and
      ampullae, whereas in many mutants only one or two of these regions were
      pigmented. There was a broad correlation between pigmentation of the stria and
      pigmentation of the vestibular region but this was not absolute. All W41/Wx,
      Wsh/Wsh, and W41/W41 mutants had some pigment on the pinna but, in contrast to
      controls where melanocytes were found in the epidermis and dermis of the pinna,
      pigment cells were reduced in number and generally restricted to the dermis.
      Injection of normal neural crest cells into 9.5-day-old mutant embryos increased
      the extent of skin pigmentation on the head and coat of adult chimeras and was
      associated with a small increase in the proportion of pigmented strias.

PMID- 7521052
TI  - [Cytokeratin-positive angiosarcoma of the adrenal gland].
AB  - Cytological, biopsy and autopsy findings in a patients suffering from massively
      metastasizing adrenal angiosarcoma are reported. Histogenetic typing of the
      tumour initially manifestating itself by osseous and liver metastases was
      problematic with regard to its partially epithelioid structure and its positivity
      upon cytokeratin immunostaining. Of relevance for the correct typing was the
      finding that the tumour cells in addition exhibited positivity for vascular
      markers. This case confirms literature data according to which cytokeratin
      expression not infrequently may be encountered in endothelial neoplasms and which
      by no means should lead to exclude such a tentative diagnosis.

PMID- 7521051
TI  - Stem cell factor regulates human melanocyte-matrix interactions.
AB  - Stem cell factor (SCF) is hypothesized to play a critical role in the migration
      of melanocytes during embryogenesis because mutations in either the SCF gene, or
      its ligand, c-kit, result in defects in coat pigmentation in mice and in skin
      pigmentation in humans. In this report we directly show that SCF alters the
      adhesion and migration of human melanocytes to extracellular matrix (ECM) ligands
      and regulates integrin expression at the protein level. SCF decreased adhesion of
      neonatal and fetal cells to collagen IV, and increased attachment of fetal cells
      to laminin. Attachment of fetal cells to fibronectin was decreased, but was
      unchanged in neonatal cells. Flow cytometry analysis of neonatal melanocytes
      showed that SCF down-regulated the expression of the alpha 2 receptor, and up
      regulated the expression of the alpha 3, alpha 5 and beta 1 integrin receptors.
      SCF down-regulated expression of alpha 2, alpha 5 and beta 1 integrins by fetal
      melanocytes, and up-regulated expression of the alpha v and alpha 3 integrin
      receptors. Analysis of melanocyte migration using time-lapse videomicroscopy
      showed that SCF significantly increased migration of neonatal, but not fetal,
      melanocytes on fibronectin (FN). We conclude that SCF regulates integrin
      expression at the protein level and that SCF has pleiotropic effects on
      melanocyte attachment and migration on ECM ligands. We suggest that this may be
      one mechanism by which SCF regulates melanocyte migration during development of
      the skin.

PMID- 7521053
TI  - [Octreotide, a somatostatin analogue].

PMID- 7521054
TI  - [The first tuberculosis cure with chemotherapy: a lupus patient in Hornheide].
AB  - Karl Wilhelm Kalkoff (1909-1981) describes in his unpublished memoirs the first
      cure of a female patient suffering from a severe form of tuberculosis cutis of
      the lupus vulgaris type. The drug used in this case was TBI/698 developed by
      Bayer Leverkusen, which was later named Conteben. This was the first
      chemotherapeutic cure of tuberculosis.

PMID- 7521055
TI  - Biotin uptake by basolateral membrane vesicles of human placenta: normal
      characteristics and role of ethanol.
AB  - This study assessed the mechanism of uptake of biotin by the fetal-facing
      (basolateral) membrane of the term human placenta. Using membrane vesicles, we
      showed that most of the uptake was attributable to transfer of the vitamin into
      the vesicle and that the uptake was saturable, Na-dependent, carrier-mediated,
      and electroneutral. The rate of uptake was less than for biotin uptake by the
      maternal-facing (apical) membrane of the human placenta. Because ethanol inhibits
      biotin uptake by the apical membrane, the effect of ethanol on uptake by
      basolateral vesicles was investigated. With 10-hr exposure at a concentration of
      2 and 3 mg/ml, but not 1 mg/ml, ethanol modestly inhibited biotin uptake. The
      mechanism of inhibition by alcohol is not known.

PMID- 7521056
TI  - [Hepatic viscerotomy (its contribution to the study of regional nosology)].
AB  - As a part of a routine yellow fever surveillance program going on in the south of
      Bahia State, Brazil, liver fragments were obtained through postmortem viscerotomy
      from 702 individuals who died after presenting acute febrile illness from 1981 up
      till 1991. Instead of being only screened for the presence of yellow fever, the
      liver tissue was thoroughly evaluated by histopathology. More than a third of the
      cases exhibited marked and diffuse steatosis occurring in malnourished infants
      and young children. Hepatic fibrosis, granulomatous disease compatible with
      disseminated tuberculosis, advanced schistosomiasis, chronic alcoholic injury,
      chronic hepatitis and cirrhosis were also frequently observed. A miscellaneous
      group of hepatic pathological processes were also recognized, which included such
      diverse entities as Hodgkin's disease, glycogenosis, sickle-cell disease,
      hepatocarcinoma, etc. Only 124 (17.7%) cases showed normal hepatic histology. The
      wide possibility of histological diagnoses strongly indicates that the material
      obtained by viscerotomy can be further explored by an interested pathologist, to
      help in the understanding of nosology and epidemiology, concerning remote
      geographic areas where viscerotomy is being routinely performed.

PMID- 7521057
TI  - Immunomodulation by soluble factors from tumor cells cultured in vivo in
      diffusion chambers.
AB  - The delayed-type hypersensitivity (DTH) response and lymphocyte-mediated
      angiogenesis were determined in mice bearing in vivo cultures of mammary tumor
      cells in diffusion chambers (DCs). Soluble tumor products which diffuse from the
      DCs were able to stimulate the immune system for both the DTH reaction and
      angiogenic activity by spleen cells.

PMID- 7521058
TI  - Mast cell phenotypic changes in skin of mice during benzoyl peroxide-induced
      tumor promotion.
AB  - The behavior of the mast cell population was analyzed during the sequential
      changes that normal mice skin undergoes during experimental two-stage
      carcinogenesis. Our study reveals that the number of mast cells increased during
      the promotion period but that this alteration is confined to the 30-microns-wide
      strip below the epidermis. A different mast cell phenotype appeared in this area,
      compatible with an MMC-like phenotype. During the carcinogenesis process, the
      mast cell population is comprised of two distinct subpopulations that appeared
      simultaneously in the same tissue, i.e. connective tissue mast cells, normally
      found in the skin of mice, and the newly formed mucosal mast cell-like cells,
      currently found in gastrointestinal mucosa.

PMID- 7521060
TI  - [Does non-conventional complementary therapies improve the quality of life of
      cancer patients? A critical literature review].
AB  - Despite substantial progress in biomedicine, a majority of advanced cancer
      diseases currently cannot be cured. In addition to conventional medical symptom
      management (palliation) and improvement of quality of life, methods of
      complementary medicine and supportive psychotherapy are increasingly applied.
      Whereas the efficacy of biomedical and psychotherapeutic interventions has been
      documented, controlled investigations of complementary methods are rare and their
      efficacy is poorly documented or is viewed controversially. Complementary methods
      are defined as methods applied by conventionally trained physicians and are based
      on tradition, or the perspective of human arts, which are not investigated or
      taught at universities. As an example of the latter, anthroposophic medicine is
      presented. Finally, we present a project developed within the scope of NFP 34,
      where the efficacy of a routine biomedical treatment is compared with an
      additional anthroposophic and psychotherapeutic intervention respectively.

PMID- 7521061
TI  - [Progress in the study of the molecular neurobiology of substance P].

PMID- 7521059
TI  - Selective antitumor effect of thioether-linked immunotoxins composed of gelonin
      and monoclonal antibody to alpha-fetoprotein or its F(ab')2 fragment.
AB  - Two thioether-linked conjugates composed of monoclonal antibody (MoAb) to alpha
      fetoprotein (AFP), 80G or its F(ab')2 fragment, and a type 1 ribosome
      inactivating protein (RIP), gelonin, were prepared as potent immunotoxins [80G-CS
      GL(IT) and F(ab')2-CS-GL(IT)]. Each conjugate contained one gelonin per 80G or
      its F(ab')2 fragment. The binding activity of these conjugates was as high as
      that of intact 80G or F(ab')2. The in vitro cytotoxic effect of F(ab')2-CS-GL(IT)
      on AFP-producing HuH-7 cells was approximately 100-fold more potent than that of
      80G-CS-GL(IT). Also, F(ab')2-CS-GL(IT) showed slight cytotoxicity against non-AFP
      producing HuH-13 cells, while 80G-CS-GL(IT) did not. On the other hand, both
      conjugates had similar selective antitumor activity against HuH-7N cells in nude
      mice, possibly due to their similar distribution in the tumor. The results
      suggest that our MoAb 80G is a suitable carrier for delivering type 1 RIP such as
      gelonin into AFP-producing hepatoma cells and that its F(ab')2 fragmentation does
      not enhance targeting efficiency.

PMID- 7521062
TI  - [Progress in the study of histamine liberators and their mechanisms].

PMID- 7521063
TI  - [The functions of nitric oxide in the nervous system].

PMID- 7521064
TI  - Vaccine technologies: view to the future.
AB  - The development of vaccines to prevent infectious diseases has been one of the
      most important contributions of biomedical science. Recent advances in the basic
      sciences are now fueling the development of a new generation of vaccines that
      will be based on rational design approaches. Two factors are making this
      possible: an improved understanding of the microbial factors required for
      virulence and the nature of the immune response to infection. The status of new
      vaccine technologies is summarized here.

PMID- 7521066
TI  - Hepatitis C virus seroprevalence in clients of sexually transmitted disease
      clinics in North Carolina.
AB  - BACKGROUND AND OBJECTIVES: The major routes of transmission for hepatitis C virus
      (HCV) appear to be blood transfusion and injecting drug use (IDU). There is still
      some controversy concerning the role of sexual transmission in HCV infection.
      GOAL OF THIS STUDY: To use a well characterized, high-risk population of STD
      clinic patients to investigate the role of sexual transmission of HCV and to
      determine any association between HCV, HBV, and HIV. STUDY DESIGN: We tested
      stored sera obtained anonymously from clients attending three STD clinics in
      North Carolina in 1988 for antibodies to HCV and hepatitis B virus (HBV). An
      anonymous, self-administered client questionnaire provided patient history and
      demographic information. RESULTS: The most important risk factor for either HCV
      or HBV seropositivity was IDU. The only risk factor associated with HCV
      seropositivity after the removal of IDUs was age older than 30 years. In
      contrast, risk factors associated with HBV seropositivity after the removal of
      IDUs included male gender, age older than 30 years, HIV seropositivity,
      homosexuality/bisexuality, syphilis seropositivity, and a history of syphilis.
      CONCLUSION: Our study of STD clients confirms the important role that IDU plays
      in infection with HCV, but suggests that sexual transmission plays only a minor
      role in HCV epidemiology.

PMID- 7521067
TI  - Self-expanding tracheobronchial stents using flexible bronchoscopy. Preliminary
      clinical experience.
AB  - Endoscopic insertion of tracheobronchial stents is indicated to achieve patency
      of the airway in case of malignant or benign obstructing lesions. Until now, the
      placement of prostheses has required a rigid bronchoscope with specially designed
      insertion instruments. Self-expanding stents are currently used to treat stenoses
      of different hollow organs (vessels, urinary tract, gastrointestinal tract, bile
      duct, respiratory tract). We report the first case of a self-expanding stent
      implanted in the trachea and right main stem bronchus using flexible
      videobronchoscope under local anesthesia. The procedure was easy, safe,
      effective, and well tolerated. No complications occurred.

PMID- 7521065
TI  - Comparison of front-line chemotherapy for aggressive non-Hodgkin's lymphoma using
      the CAP-BOP regimens. The Nebraska Lymphoma Study Group.

PMID- 7521068
TI  - Children with special health-care needs in Texas.
AB  - A comprehensive system for the delivery of care to children with special
      healthcare needs and to their families has been developed by the department of
      pediatrics of The University of Texas Health Science Center at San Antonio. A
      description of the structure and operations of this system is presented and
      offered as a model for the state of Texas.

PMID- 7521070
TI  - Adhesion of activated platelets to polymorphonuclear leukocytes.
AB  - Polymorphonuclear leukocytes (PMNL) are components of the blood which as such
      interact extensively with other blood cells, with endothelial cells or with
      plasma. Here, we consider the interaction between PMNL and platelets which is
      efficient during adhesion of platelets to PMNL and which can be studied in vitro
      using the rosette formation assay. The adhesion of activated platelets to PMNL
      seems to be mediated mainly by a protein of platelets (CD62) and its
      counterreceptor on PMNL, but also other platelet receptors are involved. Here we
      demonstrate the participation of the glycoprotein IIb-IIIa complex (CD41a) in the
      adhesion of activated platelets to PMNL due to the following findings: a)
      inhibition of adhesion by monoclonal antibodies raised against CD41a, b)
      inhibition of adhesion by peptides such as RGDS and echistatin, c) inhibition of
      adhesion by dissociation of CD41a with EGTA and d) inhibition of adhesion using
      platelets from a thrombasthenic patient which have almost no CD41a in the surface
      membrane but a normal expression of CD62 upon activation. The adhesion of
      activated platelets to PMNL via CD41a seems to be mediated by fibrinogen due to
      the following findings: a) addition of fibrinogen to ADP-stimulated and fixed
      platelets increases significantly the rosette formation and b) the incubation of
      unstimulated platelets with fibrinogen and an antibody raised against
      glycoprotein IIIa which stimulates fibrinogen binding to the platelet surface
      results in an enlarged rosette formation.

PMID- 7521069
TI  - Effect of type-1 plasminogen activator inhibitor on human leukocyte elastase.
AB  - When human leukocyte elastase (HLE) activity (1.0 microgram/ml) was analysed in
      the presence of PAI-1 (0.15.0 micrograms/ml), HLE activity, measured with the low
      molecular weight paranitroanilide substrate L-pyroglutamyl-prolyl-L-valine-p
      nitroanilide was increased time and dose dependently (a plateau of stimulation
      was reached after 30 minutes) with a simultaneous decrease in PAI-1 inhibitory
      activity. This effect was neither influenced by the presence of vitronectin nor
      heparin. When PAI-1 was converted into its latent form by incubation for 48 hours
      at 37 degrees C or incubated with an excess of recombinant t-PA to convert free
      PAI-1 into t-PA-PAI-1 complexes, the stimulatory effect of both the latent and
      the complexed form of PAI-1 was significantly greater than that of the active
      form. Analysing HLE PAI-1 interaction on a molecular level using SDS-PAGE, no SDS
      stable complex formation between HLE and PAI-1 could be observed but lower
      molecular weight cleavage products of PAI-1 were generated. The stimulatory
      effect of PAI-1 on HLE activity was not restricted to the low molecular weight
      pNA-substrate but was also revealed using a natural substrate assay (bovine neck
      ligament elastin solubilization). Therefore interaction of HLE and PAI-1 seems
      not to be restricted just to decrease PAI-1 activity but would simultaneously
      also increase HLE activity, thereby supporting enzymatic activity necessary for
      migration of leukocytes, dissolution of blood clots and tissue remodelling.

PMID- 7521072
TI  - FK 506 affects platelet aggregation in vitro.

PMID- 7521071
TI  - Cyclic nucleotide regulation of interleukin-1 beta induced nitric oxide synthase
      expression in vascular smooth muscle cells.
AB  - Experiments were performed to examine the effect of cyclic nucleotides on the
      expression of inducible nitric oxide synthase (iNOS) activity by interleukin-1
      beta (IL-1 beta) treated rat aortic smooth muscle cells (SMC). Treatment of
      vascular SMC with IL-1 beta stimulated iNOS mRNA expression and the subsequent
      release of nitrite, a stable oxidation product of nitric oxide (NO). Similarly,
      lipophilic analogues of cAMP also induced both iNOS mRNA expression and nitrite
      release. The addition of IL-1 beta and cAMP derivatives resulted in a synergistic
      enhancement of both iNOS mRNA production and of nitrite formation. In contrast,
      lipophilic analogues of cGMP did not induce iNOS expression. The addition of cGMP
      derivatives modestly increased IL-1 beta-induced SMC nitrite generation without
      affecting the production of iNOS mRNA. The capacity of cyclic nucleotides to
      positively modulate the induction of iNOS activity may play an important role in
      regulating the release of NO in vivo.

PMID- 7521073
TI  - Age-related changes in cytoskeletal components of the BDF1 mouse Sertoli cell.
AB  - Age-related changes in mouse Sertoli cell cytoskeletal components (F-actin,
      vimentin and cytokeratin) were investigated by light and transmission electron
      microscopy and immunofluorescence using BDF1 mice from 3-33 months of age. In old
      mice (30 and 33 months of age), the testicular seminiferous epithelia were
      extremely thin, containing scarce round spermatids and spermatocytes with no
      elongated spermatids. In these epithelia, the Sertoli cells had lost their
      polarity and had become flattened. F-actin was detectable at the junction between
      adjoining Sertoli cells and around the spermatid head in young mice. In old mice,
      F-actin was distributed at the junction between adjacent Sertoli cells, around
      the spermatid head, and at the luminal side of the Sertoli cell cytoplasm.
      Vimentin was detected around the Sertoli cell nucleus and extended into the
      Sertoli cell trunk towards the tubular lumen in young mice. In old mice testes,
      however, vimentin was recognized around the Sertoli cell nucleus, but not in the
      Sertoli cell trunk. Additionally, sheet-like reactions of vimentin, running
      parallel to the basement membrane, were detected near the luminal surface.
      Although cytokeratin was not detected in the Sertoli cells of mice until 27
      months of age, it was obvious in the extremely thin seminiferous epithelia of
      older mice. Cytokeratin was randomly distributed within the Sertoli cell
      cytoplasm. In these Sertoli cells, the expression of vimentin was concurrently
      detected. Detection of cytokeratin in the extremely thin seminiferous epithelia
      is one of the most characteristic phenomena of age-related testicular changes in
      Sertoli cells of older mice.

PMID- 7521074
TI  - Vasodilator mechanisms of action of amrinone do not involve the opening of either
      ATP-sensitive or Ca(2+)-activated K+ channels.
AB  - Amrinone is more coronary vasodilatory than positive inotropic compared with
      other newer phosphodiesterase inhibitors. In order to explore possible
      involvements of ATP-sensitive K+ (KATP) and large-conductance Ca(2+)-activated K+
      (KCa) channels in the vasodilator effect of amrinone, we investigated whether
      amrinone-induced vasodilation would be antagonized by glibenclamide, a blocker of
      KATP channels, or by charybdotoxin or tetraethylammonium, blockers of KCa
      channels. In isolated, blood-perfused canine papillary muscle preparations, the
      amrinone-induced increase in blood flow was not affected by glibenclamide given
      to support dogs. In canine large coronary arteries contracted with high (25 mM)
      KCl, amrinone-induced relaxation was not affected by glibenclamide, charybdotoxin
      and tetraethylammonium. These results suggest that the vasodilator mechanisms of
      amrinone do not involve the opening of either KATP or KCa channels.

PMID- 7521075
TI  - Potentiation of antitumor effect of bleomycin by local electric pulses in mouse
      bladder tumor.
AB  - C3H mice bearing subcutaneously transplanted mouse bladder carcinoma (MBT-2) were
      treated with intramuscular injection of bleomycin followed by local delivery of
      electric pulses at the tumor site. The tumors markedly reduced and even
      disappeared for several days after this treatment. Neither electric pulses nor
      bleomycin administration alone showed a significant inhibitory effect on the
      tumor growth. Thus, it is demonstrated that in mouse bladder tumor the antitumor
      effect of bleomycin can be considerably potentiated by local electric pulses.

PMID- 7521077
TI  - Impact of screening blood donors for hepatitis C antibody on posttransfusion
      hepatitis: a prospective study with a second-generation anti-hepatitis C virus
      assay.
AB  - BACKGROUND: Hepatitis C is the major cause of posttransfusion hepatitis. Blood
      components that are positive for antibody to hepatitis C virus (anti-HCV) can
      transmit posttransfusion hepatitis. STUDY DESIGN AND METHODS: To investigate the
      effect on posttransfusion hepatitis of screening blood donors with a second
      generation test for anti-HCV, 249 transfusion recipients who underwent
      cardiovascular surgery were prospectively followed. Six recipients who were
      positive for anti-HCV before transfusion and 51 subjects with incomplete follow
      up were excluded from this study. RESULTS: Eleven (13.8%) of 80 subjects who
      received unscreened blood had two successive serum alanine aminotransferase
      levels > 90 U per L. Seven (8.8% of total) developed anti-HCV and HCV RNA and two
      (2.5% of total) developed IgM antibody to cytomegalovirus (IgM anti-CMV). By
      contrast, 3 (2.7%) of the 112 subjects who received anti-HCV-screened blood had
      two successive serum alanine aminotransferase levels > 90 U per L. None of these
      three developed anti-HCV and HCV RNA, but two (1.8% of total) showed the
      development of IgM anti-CMV. The study shows that screening for anti-HCV in blood
      donors with a second-generation test almost abrogated posttransfusion viral
      hepatitis C. CONCLUSION: After anti-HCV screening, other body fluid-transmitted
      viruses such as CMV may become important in posttransfusion hepatitis.

PMID- 7521076
TI  - Role of angiogenesis in patients with cerebral ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Stroke is one of the most common causes of mortality and
      morbidity in the Western world. It results from the occlusion of a cerebral
      artery followed by severe disturbances in blood supply through microvessels to
      brain tissue. Despite an extensive literature its pathophysiology is poorly
      understood, and this has severely impeded the logical development of therapy.
      METHODS: Brains were obtained from 10 patients aged 46 to 85 years with survival
      times of 5 to 92 days after their stroke. Infarcted areas and representative
      control tissues from the contralateral uninvolved brain hemisphere were
      collected. Microvessel density was measured microscopically. A total of 6520
      microvessels were scored in 10,801 areas. The level of activation of the
      endothelial cells was studied by immunohistochemistry using three monoclonal
      antibodies, viz, E-9, raised against activated endothelial cells; IG11,
      recognizing vascular cell adhesion molecule-1; and anti-proliferating cell
      nuclear antigen. Angiogenic activity in tissue extracts was examined using an in
      vivo chicken chorioallantoic membrane assay. RESULTS: There was a statistically
      significant increase in the number of microvessels (Wilcoxon log-rank test; P <
      or = .01) in 9 of 10 infarcted brain tissues when compared with their
      contralateral normal hemisphere. In these patients the higher blood vessel counts
      correlated with longer survival, as ascertained by Spearman's p analysis (P <
      .02). The number of microvessels filled with blood cells was significantly lower
      in the infarcted hemispheres (P < .01). In contrast, statistically significant
      increased numbers of empty microvessels occurred in infarcted tissues compared
      with the contralateral hemisphere. Monoclonal antibody E-9 reacted weakly with
      normal-brain vascular endothelial cells; anti-proliferating cell nuclear antigen
      and IG11 were virtually negative. All three antibodies strongly stained the blood
      vessels of stroke tissues. The stroke tissues contained angiogenic activity, as
      shown by the induction of new blood vessels in a chorioallantoic membrane assay.
      CONCLUSIONS: We have shown that stroke causes active angiogenesis that is more
      developed in the penumbra. Further experiments are needed to determine if this
      angiogenesis has beneficial effect.

PMID- 7521078
TI  - Hepatitis C virus antibody seroconversion in a volunteer blood donor.

PMID- 7521081
TI  - Brain-imaging studies of cognitive functions.
AB  - Little is understood about the brain, the mind and their relationships. However,
      rapid technical advances in brain-imaging devices such as positron emission
      tomography (PET), functional magnetic resonance imaging, EEG and EMG have
      increased the capabilities for visualizing the working brain, and uncovering the
      cerebral areas participating in the realization of cognitive tasks, and progress
      in cognitive science has led to a better understanding of the functional
      architecture of mental abilities. There is, therefore, considerable potential for
      achieving a greater understanding of the relationships between cognition and
      cerebral structures through brain-imaging studies of mental functions. However,
      these studies are confronted with a series of difficulties related to the
      assumptions that govern their application, the constraints imposed by these
      techniques on the design of cognitive experiments, the complexities inherent in
      establishing relations between cognition and anatomy through physiology, and to
      the interpretation of patterns of cerebral activation. In this article, potential
      difficulties are described drawing essentially on examples from PET studies of
      cognitive functions. Whereas a bright future lies ahead for the study of human
      brain mapping, many problems still have to be overcome and solved in order to
      exploit the full potential of new brain-imaging techniques.

PMID- 7521080
TI  - Cognitive functions of cortical ACh: lessons from studies on trans-synaptic
      modulation of activated efflux.
AB  - Trans-synaptic modulation of cortical ACh efflux is a useful approach for
      determining the functions of cortical ACh. Bilateral modulation of basal
      forebrain GABAergic transmission by benzodiazepine-receptor agonists and inverse
      agonists decreases and increases, respectively, activated cortical ACh efflux.
      The determination of behavioral functions which are mediated via activated
      cortical ACh efflux, and therefore subject to the effects of basal forebrain GABA
      cholinergic manipulations, should promote analyses of the functions of cortical
      ACh. Trans-synaptic approaches to enhance activated cortical ACh efflux offer
      some potential for the treatment of cognitive dysfunctions associated with
      impaired cortical cholinergic transmission.

PMID- 7521082
TI  - The ladder of progress in neuroscience.

PMID- 7521079
TI  - Evidence that increases in lymphocyte tyrosine phosphorylation precede cardiac
      allograft rejection. Effects of cyclosporine and potential use in clinical
      management.
AB  - Tyrosine phosphorylation is an early, critical event in lymphocyte signal
      transduction. We measured tyrosine phosphorylation in a porcine experimental
      transplant model to evaluate its utility in monitoring the allograft immune
      response. Using flow cytometry, we demonstrate a biphasic increase in
      phosphotyrosine (ptyr) levels in peripheral blood mononuclear cells (PBMC), and
      that increases are detectable as early as 1 day posttransplantation in untreated
      transplanted animals (n = 4). This biphasic response is likely result from the
      sequestration of ptyr+ cells from the periphery into the graft as graft
      infiltrating lymphocytic cells show increased ptyr levels. This suggests possible
      lymphocyte trafficking between the peripheral compartment and the allograft. A 5
      day course of treatment with cyclosporine (CsA) at 20 mg/kg/day (n = 4), but not
      at 10 mg/kg/day (n = 4), prevents graft rejection in this allograft model.
      Strikingly, treatment with 20 mg/kg/day CsA, but not with 10 mg/kg/day,
      suppressed increases in ptyr levels in both PBMC and graft-infiltrating cells.
      Increases in ptyr levels in PBMC are detectable 2-5 days before histologic and
      electrocardiographic signs of graft rejection, suggesting a potential diagnostic
      utility for measuring tyrosine phosphorylation in monitoring and managing
      transplant rejection.

PMID- 7521084
TI  - Pattern formation in the vertebrate neural plate.
AB  - Recent advances have been made in the understanding of the cellular and molecular
      mechanisms involved in the formation and patterning of the neural plate of
      vertebrate embryos. Both planar and vertical signaling pathways appear to be
      involved in the neural induction and axial patterning of the neural plate. The
      neural plate, behaving as a developmental field, might be patterned by signals
      emanating from boundary regions: the organizer region and the midline and edges
      of the neural plate. Here, A. Ruiz i Altaba describes a possible model for
      anteroposterior patterning involving ;lanar signals for amphibian, avian and
      mammalian embryos, compares the axial patterning of the neural plate with the
      patterning of insect epithelia, and discussed possible roles of noggin,
      follistatin and hedgehog-related genes in neural induction and patterning.

PMID- 7521083
TI  - Modulatory functions of neurotransmitters in the striatum: ACh/dopamine/NMDA
      interactions.
AB  - The striatum is viewed as a structure performing fast neurotransmitter-mediated
      operations through somatotopically organized projections to medium-size spiny
      neurons. This view is contrasted with another view that depicts the striatum as a
      site of diffuse modulatory influences mediated by cholinergic interneurons and by
      dopamine and N-methyl-D-aspartate receptors. These two operational and
      organizational modes both contribute, through their mutual interaction, to the
      function of basal ganglia. Detailed knowledge of the neural mechanisms by which
      such interactions take place and are expressed into behaviour, can provide new
      insight into the physiopathology and new clues for therapy of disorders of basal
      ganglia.

PMID- 7521085
TI  - Direct spinal pathways to the limbic system for nociceptive information.
AB  - The hypothalamus is believed to play important roles in several aspects of
      nociception. Previously, nociceptive information was thought to reach
      hypothalamic neurons through indirect, multisynaptic pathways. However, we have
      found that thousands of neurons throughout the length of the spinal cord in rats
      send axons directly into the hypothalamus, and many of these axons carry
      nociceptive information. The axons often follow a complex course, ascending
      through the contralateral spinal cord, brainstem, thalamus and hypothalamus. They
      then cross the midline and enter the ipsilateral hypothalamus, turn posteriorly,
      and continue into the ipsilateral thalamus. These axons might provide nociceptive
      information to a variety of nuclei in the thalamus and hypothalamus bilaterally.

PMID- 7521087
TI  - Dendritic processing of synaptic information by sensory interneurons.
AB  - One of the most distinguishing features of nerve cells is the vast morphological
      diversity of their input regions, that is, their dendrites. These range from
      bulbous structures, with only small protrusions, to large tree-like
      arborizations. The diversity of nerve cells is further augmented by a
      continuously increasing number of types of voltage-dependent conductances in
      dendrites that might alter the postsynaptic signals in a pronounced way.
      Moreover, intracellular factors such as Ca2+ link electrical activity with
      biochemical processes, and can induce short and long-term changes in
      responsiveness. This complexity of neurons in general, and the uniqueness of each
      cell type, sharply contrasts with the comparatively simple and uniform design
      principle of the integrate-and-fire units of so-called neuronal net models. This
      raises the question of which particular structural and physiological details of
      nerve cells really matter for the performance of neuronal circuits. An answer to
      this basic problem of computational neurobiology might be given only if the task
      of the neurons and circuits is known. This review illustrates how the problem can
      be approached particularly well in sensory interneurons. The functional
      significance of sensory interneurons can often be assessed more easily than that
      of central nerve cells because of their vicinity to the sensory surface.

PMID- 7521086
TI  - The early events of oxygen and glucose deprivation: setting the scene for
      neuronal death?
AB  - It is generally thought that neuronal death caused by a reduction in oxygen or
      glucose supply, or both, occurs as a result of massive increases in the
      extracellular concentrations of excitatory amino acid neurotransmitters,
      particularly glutamate. A pertinent question is what happens before this
      increase, because measures which prevent extracellular accumulation of glutamate
      could have potential for clinical use in, for example, management of acute
      stroke. This article will review the major pathophysiological responses which
      occur up until the time of accumulation of glutamate. Withdrawal of energy
      substrate quickly leads to modest changes in membrane potential and intracellular
      and extracellular ion concentrations. Depression of action-potential-dependent
      synaptic transmission occurs a little later and might, in part, reflect actions
      of adenosine. Increases in the extracellular concentration of excitatory amino
      acids to neurotoxic levels take place only as membrane potential falls rapidly
      towards 0mV, coincident with massive changes in ion gradients.

PMID- 7521088
TI  - Immunocytochemical detection and phenotypic characterization of micrometastatic
      tumour cells in bone marrow of patients with prostate cancer.
AB  - Monoclonal antibodies (mAbs) specific for cytokeratins are potent probes for the
      identification of disseminated individual epithelial tumour cells in mesenchymal
      organs such as bone marrow. We have used a monoclonal antibody (mAB) against
      cytokeratin 18 (CK18) for the detection of individual metastatic tumour cells in
      bone marrow aspirates from 84 patients with carcinoma of the prostate. CK18+
      cells were detected in a sensitivity of 1 per 8 x 10(5) marrow cells using the
      alkaline phosphatase anti-alkaline phosphatase (APAAP) system for staining. We
      were able to detect CK18+ tumour cells in the marrow of 33% of patients with
      stage N0M0 prostate cancers. The incidence of CK18+ cells showed a significant
      correlation with established risk factors, such as local tumour extent, distant
      metastases and tumour differentiation. For further characterization of such cells
      in patients with prostate cancer, we developed an immunocytochemical procedure
      for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate
      specific antigen (PSA). In a first step, cells were incubated with a murine mAb
      against PSA, followed by gold-conjugated goat anti-mouse antibodies. In a second
      step, a biotinylated mAb to CK18 was applied as primary antibody and subsequently
      incubated with complexes of streptavidin-conjugated alkaline phosphatase, which
      were developed with Newfuchsin substrate. The binding of gold-labelled antibodies
      was visualized by silver enhancement. CK18+ cells co-expressing PSA were found in
      bone marrow aspirates from 5 out of 14 patients with carcinomas of the prostate.
      The specificity of CK18 for epithelial tumour cells in bone marrow was supported
      by negative staining of 12 control aspirates from patients with benign prostatic
      hyperplasia (BPH).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521090
TI  - Effect of dosing regimen on efficacy and safety of doxazosin in normotensive men
      with symptomatic prostatism: a pilot study.
AB  - OBJECTIVES: In this pilot study, the effect of dosing schedule on the efficacy
      and safety of the long-acting alpha 1-adrenergic blocker doxazosin (DOX) was
      evaluated in 48 consecutive, normotensive men (mean age, 61.2 years) with
      symptoms of prostatism. METHODS: In this titration to fixed dose study, patients
      were randomized into 1 of 4 treatment groups: (1) 4 mg DOX once in the AM (n =
      12); (2) 4 mg DOX once in the PM (n = 12); (3) 8 mg DOX once in the AM (n = 12);
      and (4) 8 mg DOX once in the PM (n = 12). Parameters evaluated included Boyarsky
      symptom score (Sx), peak uroflow (Qmax), blood pressure, and occurrence of side
      effects. Once stabilized, patients were seen at 3-month intervals; follow-up
      ranged from 3 to 19 months (mean, 7.7). RESULTS: Clinical improvement as
      determined by Sx and Qmax was similar for AM and PM groups with either 4 or 8 mg
      of DOX. Mean decreases in Sx at 3 months were 4.6, 4.2, 5.1, and 5.2 and at 6
      months were 4.7, 4.7, 5.3, and 5.4 for the 4 mg AM, 4 mg PM, 8 mg AM, and 8 mg
      PM, respectively. Mean peak uroflow at 3 months increased 2.7, 2.9, 3.2, and 3.3
      mL/s and at 6 months increased 2.6, 3.0, 3.4, and 3.5 mL/s for the 4 mg AM, 4 mg
      PM, 8 mg AM, and 8 mg PM, respectively (p < 0.05). Six patients (13%) were
      dropped from the study because of side effects (2 for fatigue, 2 for headache, 2
      for dizziness): 5 during the titration phase (4 mg AM: 2; 8 mg AM: 2; 8 mg PM:
      1), and 1 during the treatment phase (8 mg AM). CONCLUSIONS: These data suggest
      that evening dosing does not diminish efficacy yet may enhance toleration of DOX.
      These preliminary results suggest that a larger prospective study is warranted to
      determine the optimal dosing and timing of DOX in the management of symptomatic
      benign prostatic hyperplasia.

PMID- 7521089
TI  - Studies on calcium oxalate monohydrate crystallization: influence of inhibitors.
AB  - A simple model to study calcium oxalate monohydrate (COM) crystallization on
      different substrates is presented and the action of different potential
      inhibitors is evaluated and discussed. COM heterogeneous nucleation was assayed
      on solid surfaces as calcium phosphate, mixtures of mucin with calcium phosphate,
      and wax. In the presence of a non-protected non-renewed solid surface in contact
      with normal urine, COM crystal formation could be detected at short intervals (3
      h). The most active heterogeneous nucleation capacity corresponded to calcium
      phosphate. In the presence of 10% mucin, owing to the renewal of the surface
      layer no COM crystal were detected on the pellet's surface. The study of citrate
      and pentosan polysulphate (a semisynthetic polysaccharide) on COM heterogeneous
      nucleation demonstrated some important inhibitory effects when concentration
      increased and time decreased. Maximum effects were selectively manifested on
      calcium phosphate surfaces. Only phytic acid at adequate concentration exhibited
      a total inhibitory capacity of COM formation, even during longer intervals (15
      h).

PMID- 7521091
TI  - The North American experience with the UroLume endoprosthesis as a treatment for
      benign prostatic hyperplasia: long-term results. The North American UroLume Study
      Group.
AB  - OBJECTIVES: To determine the efficacy and safety of the UroLume endoprosthesis as
      a treatment for obstructive benign prostatic hyperplasia in healthy men. METHODS:
      One hundred twenty-six men were enrolled prospectively in a multicenter North
      American Clinical Trial. Ninety-five men (mean age 68 +/- 7 years) had moderate
      or severe prostatism, whereas 31 participants (mean age 76 +/- 8 years) were in
      urinary retention. Voiding function for all patients was assessed prior to stent
      placement and in follow-up at 1, 3, 6, 12, and 24 months with the Madsen-Iversen
      symptom questionnaire, peak urinary flow rate, postvoid residual urine volume,
      and cystoscopic examination. RESULTS: For the nonretention cohort at 24-month
      follow-up, the results were as follows: (1) total symptom score decreased from
      14.3 +/- 0.5 preinsertion to 5.4 +/- 0.5 (p < 0.001); (2) peak urinary flow rate
      increased from 9.1 +/- 0.5 mL/s preinsertion to 13.1 +/- 0.7 mL/s (p < 0.001);
      and (3) postvoid residual urine volume decreased from 85 +/- 9 mL to 47 +/- 8 mL
      (p = 0.02). For the retention group, the total symptom score, peak urinary flow
      rate, and postvoid residual urine volume at 24 months were 4.1 +/- 0.5, 11.4 +/-
      1.0 mL/s and 46 +/- 7 mL, respectively. By 12-month follow-up, most
      endoprostheses were completely covered with urothelium. Although significant long
      term complications were minimal, 17 endoprostheses have been explanted for an
      overall removal rate of 13%. All devices were removed transurethrally without
      subsequent sequelae to the external urinary sphincter or urethra. CONCLUSIONS:
      The long-term results from this North American Clinical Trial suggest that the
      UroLume endoprosthesis can be an effective and safe treatment for properly
      selected healthy men with obstructive benign prostatic hyperplasia. Randomized
      clinical trials comparing this minimally invasive procedure with transurethral
      resection of the prostate are now underway to document further its efficacy and
      safety.

PMID- 7521092
TI  - A modified prostatic UroLume Wallstent for healthy patients with symptomatic
      benign prostatic hyperplasia: a European Multicenter Study.
AB  - OBJECTIVES: This European multicenter study was aimed to assess the clinical
      reliability of a modified prostatic UroLume Wallstent (American Medical System,
      Minnetonka, MN) in the treatment of 135 healthy patients with symptomatic benign
      prostatic hyperplasia. METHODS: Ninety-one patients who were obstructed but still
      voiding spontaneously and 44 patients who had an indwelling catheter were treated
      by placement of a modified stent. RESULTS: A significant improvement in mean peak
      flow rates and residual urine volumes was maintained throughout follow-up. Both
      obstructive and irritative voiding symptoms were significantly improved after
      placement of the stent, although a greater amelioration was seen in obstructive
      symptoms. The rate of patients reporting erections increased after stent
      insertion. Eighty percent of sexually active patients reported the maintenance of
      antegrade ejaculation postoperatively. A greater than 80% epithelialization of
      the stent was seen in 28 patients (100%) examined at the 18-month follow-up. Long
      term complications were seen in 51 patients (38%). Twenty-one of these patients
      had the stent removed due to intractable detrusor instability, stent
      encrustation, stent migration, or persistence of obstruction due to prominent
      median lobe, understenting, or severe hyperplasia of the epithelium of the
      prostatic urethra. In 6 of them another stent was reimplanted while the others
      were treated surgically. CONCLUSIONS: Although this modified stent was abandoned
      due to an unacceptable rate of complications, this study demonstrates that
      bladder outlet obstruction in healthy patients with benign prostatic hyperplasia
      can be successfully relieved by the placement of a UroLume Wallstent.

PMID- 7521093
TI  - Systematic biopsies accurately predict extracapsular extension of prostate cancer
      and persistent/recurrent detectable PSA after radical prostatectomy.
AB  - OBJECTIVES: To determine if methodic analysis of systematic echo-guided biopsies
      associated with prostatic-specific antigen (PSA) and PSA density can accurately
      predict the actual pathologic stage of prostate cancer (Ca P). METHODS: One
      hundred patients with clinically localized (T1, T2) Ca P who underwent radical
      prostatectomy (RP) were preoperatively staged by digital rectal examination
      (DRE), measurement of serum PSA (Yang Pros-check) and PSA density (PSAD), and
      transrectal echo-guided systematic biopsies (three in each lobe aiming to sample
      prostatic capsule) to evaluate T stage, Gleason grade, number of positive
      biopsies, and presence of cancer in the periprostatic tissues. Radical
      prostatectomy specimens were processed following the McNeal method. The PSA
      levels were measured every month for 2 years. RESULTS: Extracapsular disease was
      detected on the specimen in 45% of the patients, persistent/recurrent detectable
      PSA in 47% (mean follow-up 18 months). Clinical stage T2 B, presence of Gleason
      grade 4, PSA > 25 ng/mL, PSAD > 0.6, number of positive biopsies > 66% of the
      total number of cores taken had a positive predictive value (PPV), respectively,
      of 72%, 66%, 80%, and 87%. Periprostatic tissue was evaluable on the core
      biopsies in 77% of the cases. Presence of cancer in the periprostatic fat on the
      core biopsies had a PPV of 94% for extracapsular disease/biological recurrence.
      CONCLUSIONS: The presence of extracapsular cancerous tissue on prostatic core
      biopsies accurately predicts extracapsular extension of Ca P. Therefore, care
      should be taken when performing prostate biopsies to sample the prostate capsule
      and surrounding tissues to obtain a more accurate staging of the disease. The
      second best predictor of extracapsular disease is the percentage of positive
      biopsies.

PMID- 7521094
TI  - Phase II trial of 5-fluorouracil and alpha-2b interferon in patients with hormone
      refractory metastatic prostate cancer.
AB  - OBJECTIVES: Metastatic prostate cancer remains a disease with no effective
      therapy. We treated 13 patients with hormone-refractory metastatic prostate
      cancer with 5-fluorouracil (5-FU) and alpha-2b interferon. Our objectives were to
      determine the response rate and toxicity of recombinant alpha interferon and 5-FU
      in patients with hormone-refractory metastatic prostate cancer. METHODS: Patients
      with progressive hormone-refractory metastatic prostate cancer with adequate
      hematologic and renal function underwent baseline bone scans, computed
      tomographic (CT) scans of abdomen and pelvis, and measurement of prostate
      specific antigen (PSA). Therapy consisted of a 5-day loading course of 5-FU at
      500 mg/m2 with alpha-2b interferon 9 million units subcutaneously 3 times weekly
      followed by weekly 5-FU and alpha interferon 3 times per week. RESULTS: When PSA
      was used as a response parameter with modified National Prostatic Cancer Project
      (NPCP) criteria, no objective responses were seen. Using NPCP criteria alone, 5
      patients had stable disease. Post-therapy PSA values increased from baseline in 8
      of 11 patients (2% to 72%) and declined in 3 patients (3% to 16%). Frequent
      dosage modifications were required with the dose intensity of 5-FU and alpha
      interferon of 57% and 58%, respectively. Toxicity was significant, with 31% of
      patients having grade 3 to 4 mucositis and 46% grade 3 to 4 fatique. CONCLUSIONS:
      5-FU and alpha interferon, when administered at the dosage and schedule utilized
      in this study, have no clinically significant activity and are associated with
      unacceptable toxicity in patients with metastatic prostate cancer. The role of
      PSA as an indicator of response remains unclear.

PMID- 7521095
TI  - Soluble Mycobacterium bovis protein antigens: studies on their purification and
      immunological evaluation.
AB  - The eradication of bovine tuberculosis is an ultimate aim of the beef industry
      and the development of accurate diagnostic tests will expedite eradication.
      Characterization of Mycobacterium bovis antigens, and a detailed understanding of
      their immune reactivity will aid in the development of more specific and
      sensitive diagnostic tests. With this aim, studies were conducted which have
      resulted in the purification and immunological characterization of the major
      soluble M. bovis antigens. The purified antigens were found to contain cross
      reactive epitopes and immunological responses to these proteins varied among
      individual animals. Thus if more specific diagnostic tests are to be formulated,
      they will have to be at the epitope level, using only species-specific epitopes
      and not whole proteins. Due to the genetic diversity of the response of infected
      cattle to individual epitopes, a large cocktail of such epitopes will be
      necessary for the development of a sensitive test.

PMID- 7521096
TI  - Use of lambda gt11 to identify antigenic components of equine herpesvirus 4.
AB  - A library of the equine herpesvirus 4 (EHV-4) genome was constructed in the
      lambda gt11 expression vector. Recombinant bacteriophage expressing EHV-4
      antigens as beta-galactosidase fusion proteins were detected with rabbit
      antiserum raised against EHV-4 virions and convalescent horse serum. EHV-4 DNA
      sequences contained in the immunopositive recombinants were used as hybridization
      probes for mapping the genes encoding the antigens on the viral genome. The DNA
      sequence of the probes was determined. Screening the library with rabbit
      antiserum led to the identification of 40 recombinants, 26 of which were further
      characterized. Determination of the DNA sequence of the EHV-4 inserts revealed
      that 23 of the recombinants encode an identical portion of glycoprotein gB. Two
      of the recombinants encode a portion of the previously unidentified EHV-4
      homologue of the EHV-1 immediate early protein. The EHV-4 insert of the remaining
      recombinant encodes a portion of the previously unidentified EHV-4 homologue of
      herpes simplex virus 1 (HSV-1) UL36, a tegument protein. Screening the library
      with horse serum led to the identification of three recombinants, one of which
      encodes the same gB sequence as the gB recombinant recognized with the rabbit
      serum. The other two contain overlapping sequences that encode a portion of EHV-4
      gX.

PMID- 7521097
TI  - [The localization and preliminary characteristics of antigenic sites (B epitopes)
      in the nucleocapsid protein of the Lassa virus].
AB  - Nucleocapsid protein of Lassa virus contains 4 epitope sites. Three of them were
      localized in amino acid position 123-1 27, 337-346, and 518-527. Monoclonal
      antibody 1108 specific to Lassa virus NP-protein reacted with 123-127 synthetic
      peptide in solid-phase ELISA and precipitated nucleocapsid proteins of Machupo,
      Tacaribe, and Mopeia arenaviruses in RIP.

PMID- 7521098
TI  - [The antigenic structure of influenza B viruses isolated in 1991].
AB  - A comparative immunological analysis of the antigenic structure of reference
      influenza B viruses of 1940-1984 and isolates of 1986-1991 using monospecific
      antibodies to individual antigenic determinants and monoclonal antibodies to
      hemagglutinin of B/Oregon/5/80 virus demonstrated a further antigenic drift of
      influenza B viruses from the reference variants B/Victoria/2/87 and
      B/Yamagata/16/88. Alongside with circulation of viruses with new antigenic
      properties, variants were found in the epidemic outbreak of 1991 whose
      hemagglutinin had common antigenic markers with those of variants of the previous
      years.

PMID- 7521099
TI  - [The specific activity and immunological safety of the intranasal method of
      revaccination with a live measles vaccine made from the Leningrad-16 strain].
AB  - The search for alternative routes for administration of live measles vaccine is
      associated both with the threat of infection with human immunodeficiency virus,
      hepatitis B virus, and with the development of a more physiological, natural and
      less traumatic mode of vaccine administration. The influence of the intranasal
      administration on the general condition of the immune system, its
      immunomodulating effect (the emergence of inducer suppressors, cell response to
      the inactivated virus), was studied as well as the level and intensity of
      secretory and general humoral immunity. The studies confirmed the immunological
      effectiveness and safety of the intranasal administration of a live measles
      vaccine and suggested its advantages for revaccination against measles.

PMID- 7521100
TI  - [The antigenic structure of the eastern equine encephalomyelitis virus studied by
      using monoclonal antibodies].
AB  - Thirty-three monoclonal antibodies (Mabs) interacting with the structural
      proteins of Eastern equine encephalomyelitis (EEE) virus were prepared. The
      mutual arrangement of the antigenic sites on the E1 and E2 glycoproteins was
      studied by competitive radioimmunoassay. At least four nonoverlapping sites were
      found on the E1. The E2 glycoprotein contained at least seven partially
      overlapping antigenic sites. Mabs to the sites E2-2 and E2-3 neutralized viral
      infectivity and blocked hemagglutination. Mabs to the site E2-1 blocked
      hemagglutination. Mabs to sites E2-2, 3, and 7 protected mice against lethal
      infection although the protective Mabs to sites E2-2b and E2-7 did not neutralize
      the virus. The antibodies to the other three sites of E2 and to all sites of E1
      did not have any biological activity. The experimental results indicate the
      dominant role of E2 in antiviral immunity, over 98% of the observed protective
      effect being associated with the E2-2 site.

PMID- 7521101
TI  - [An immunosorbent for interferon purification].
AB  - Immunoaffinity chromatography was shown to be the method achieving the most
      complete elimination of antigenic admixtures from leukocyte interferon
      preparations without the loss of the preparation activity. An affinity sorbent
      has been developed on the basis of covalently linked polyvinyl alcohol (PVA). The
      immobilization of the antigen-specific rabbit globulin in the preparation of the
      sorbent is achieved by reaction of protein amino groups with the activated
      matrix. The proposed sorbent achieved the elimination of the antigenic admixtures
      from interferon preparations as effectively as those prepared on the basis of
      sepharose 4B, the productivity of the purification process being at least 5 times
      higher. The proposed sorbent is stable at the limit values of rH, is not
      destroyed by detergents, is sterilized in the process of preparation. Owing to
      the strong linkage of the immobilized immunoglobulin with the PVA-carrier,
      immunoaffinity chromatography on this sorbent does not involve contamination of
      the preparations with rabbit globulin allergenic for man. The combination of a
      large pore structure, wetting ability, stiffness, mechanical and chemical
      stability allows the proposed sorbent to be recommended for use in modern large
      scale biotechnological production.

PMID- 7521102
TI  - Langerhans' cells and lymphocytic infiltrate in AIDS-associated Kaposi's sarcoma.
      An immunohistochemical study.
AB  - The epidermal Langerhans' cells are dendritic cells of the skin capable of
      triggering cutaneous immune responses. They possess the membrane antigens
      required to this effect: class II histocompatibility antigen, CD1a and CD4; the
      latter acts as receptor for the human immunodeficiency virus. The skin is the
      organ primarily affected by Kaposi's sarcoma (KS). In epidemic KS, the local
      immunologic conditions of the skin are little known. We therefore studied 12
      patients with AIDS-associated KS, evaluating the density and phenotypic
      expression in KS-affected and unaffected skin of the following antigens: CD1a,
      HLA-DR, CD4 in dendritic epidermal cells and dermis, and CD3, CD4 and CD8 in
      cells of the inflammatory infiltrate, using monoclonal antibodies applied to
      frozen sections with the avidin-biotin-peroxidase technique. Langerhans' cells in
      the AIDS-KS skin lesions were found to be decreased in number. This decrease was
      even more pronounced in the case of cells expressing HLA-DR antigen. A number of
      them were also revealed with CD4. The tumour lymphocytic infiltrate was almost
      exclusively composed of CD3+ CD8+ phenotype lymphocytes. The dermis also revealed
      CD4+ dendritic cells. The basal keratinocytes focally expressed HLA-DR. These
      phenotypical alterations of the Langerhans' cells and the local immunological
      imbalance observed may contribute to the growth and continuity of the KS lesions.

PMID- 7521103
TI  - Immunophilins and immunosuppression by cyclosporins and macrolide structures.

PMID- 7521105
TI  - Plasma neuropeptide levels in psoriasis.
AB  - The immune system is important in the pathogenesis of psoriasis and emotional
      stress has precipitated psoriasis in many patients. Neuropeptides, alpha
      Melanocyte stimulating hormone (alpha-MSH), beta-endorphin, met-enkephalin and
      substance P (SP) act as immunomodulators, and their secretion increases during
      periods of stress. To see whether these neuropeptides themselves might be related
      to psoriasis and/or to the aggressiveness of the disease, we evaluated the plasma
      neuropeptide levels in 13 patients with active psoriasis (patients with new
      lesions and/or pre-existing lesions that had become larger during the month
      before the study), in 11 patients with stable psoriasis and in 10 healthy
      controls. Plasma concentrations of neuropeptides were evaluated by RIA
      (immunoradiometric assay for beta-endorphin). Data were compared by the Student t
      test for unpaired data. There were no significant differences between the plasma
      levels of any of the neuropeptides between active psoriatic patients and stable
      psoriatic patients, nor between the plasma levels of neuropeptides of psoriatic
      patients and those of control subjects. It seems unlikely that circulating
      neuropeptide levels are of primary importance in the manifestation of the
      psoriatic skin lesions.

PMID- 7521104
TI  - Differential expression of ICAM-1, E-selectin and VCAM-1 by endothelial cells in
      psoriasis and contact dermatitis.
AB  - Adhesion receptors on endothelial cells are considered to be important for
      cellular influx in tissue. In this regard, skin constitutes a specialised
      environment for migration of leukocytes during inflammation. Using immuno
      enzymatic staining techniques, we compared the in situ expression of ICAM-1, E
      selectin, and VCAM-1 on endothelial cells and inflammatory infiltrates in both
      lesional and non-lesional biopsied skin from two immuno-inflammatory diseases,
      viz. psoriasis and contact dermatitis. The results were compared with those in
      skin specimens obtained from normal healthy individuals free from any history of
      skin disease. Our results show that ICAM-1 and ELAM-1 are upregulated in
      psoriatic non-lesional and lesional skin. On the other hand, in non-lesional
      biopsy from contact dermatitis patients, all three AR molecules are sparsely
      present, similar to the situation in normal skin although they are overtly
      expressed in the lesional sites. Moreover, VCAM-1 was found to be significantly
      increased on endothelial cells in the lesional sites of contact dermatitis as
      compared with biopsied psoriatic specimens. Interestingly VCAM-1 was also found
      to be present on some T-cells and Langerhans cells in contact dermatitis alone.
      The present data suggest that in different inflammatory dermatitis, varying
      adhesion receptor-ligand interactions involving endothelial cells and leukocytes
      are involved, which may be due to the differing cytokine profiles of
      perivascularly located T-cells.

PMID- 7521106
TI  - Quantitative analysis of soluble cell adhesion molecules in otitis media with
      effusion.
AB  - The levels of the soluble intercellular adhesion molecule 1 (sICAM-1) and soluble
      granule membrane protein-140 (sGMP-140) were measured in middle ear effusions
      (MEEs) of otitis media (OM) with ELISA. MEEs of chronic serous and mucoid OM in
      children contained significantly higher levels of sICAM-1 and sGMP-140 compared
      with normal serum. sGMP-140 in acute and chronic OM in children was higher than
      in adult chronic serous OM, and in acute purulent OM higher chronic serous OM in
      children. Cytologic analysis showed that the mean level of sGMP-140 was
      significantly higher in the neutrophil dominant group than in other groups except
      the few cells type. sICAM-1 showed no differences among the cytologic
      classifications. Copious amounts of sICAM-1 and sGMP-140 in MEEs were observed in
      this study, and were probably the result of shedding from the cells expressed
      cell adhesion molecules. These cell adhesion molecules in MEEs were thought to
      modify the inflammatory response in OM.

PMID- 7521107
TI  - Antigen expression of epithelial markers, collagen IV and Ki67 in middle ear
      cholesteatoma. An immunohistochemical Study.
AB  - The expression of epithelial markers (cytokeratins, Filaggrin, BerEp4 and EMA),
      collagen IV and Ki67 was studied immunohistochemically in cholesteatoma and
      compared with that in epidermis of meatal skin, squamous epithelium of eardrum
      and simple epithelium of middle ear mucosa. MNF116 (cytokeratin 10, 17, 18)
      stained the full layer of normal epithelium and all cholesteatoma specimens. CK10
      and Filaggrin were expressed in the upper layer of epidermis but more diffusely
      in cholesteatoma. BerEp4 was found in the basal layer of normal epithelium but
      was detected in most epithelial cells in cholesteatoma matrix. Variability was
      observed in EMA and CK14 immunostaining. Collagen IV was localized in the
      basement membrane of normal epithelium with a continuously staining pattern, an
      observation also made in the cholesteatomas studied. However, in one of these
      small areas the basement membrane was not stained with collagen IV. Ki67 was
      expressed in nuclei of the cells in the basal layer of normal epithelium but
      extended to epithelial cells in the upper layers of cholesteatoma matrix. The
      results of the present study indicate that the expression pattern of epithelial
      markers in cholesteatoma corresponds to that in normal epidermis. The increasing
      expression of BerEp4 and Ki67 confirms the hyperproliferative nature of
      cholesteatoma. Whether or not the lack of expression of collagen IV in one of the
      cholesteatomas reflects a true degradation of the basement membrane needs further
      investigation in extended materials.

PMID- 7521108
TI  - Presence of neuropeptides in human nasal polyps.
AB  - The pathophysiological effects of non-cholinergic, non-adrenergic neuropeptides
      are well known in the nasal mucosa, but unclear in the polyps. Since the
      pathophysiological roles of neuropeptides depend on their presence in the target
      tissue, specimens of nasal polyps were removed from 20 patients and examined for
      the presence of vasoactive intestinal peptide (VIP), neuropeptide Y (NPY),
      dopamine-beta-hydroxylase (DBH), substance P (SP) and calcitonin gene-related
      peptide (CGRP). To visualize these neuropeptide fibers, immunohistochemical
      staining by the peroxidase-anti-peroxidase method and color reaction by Nickel
      enhancement of diaminobenzidine (DAB) were used. Fine varicose neuropeptides
      immunostained fibers were predominantly distributed in the pedicle of the polyps.
      No neuropeptides were found in the mucosal epithelium and subepithelium. NPY
      fibers were predominantly seen around the thick wall vessels, whereas the VIP
      fibers were mainly to be found in close proximity to the submucosal glands and
      fairly close to the vessels. SP or CGRP fibers were not found in the polyps. VIP
      and NPY in the pedicle of the polyps may be present in connection with mucosal
      inflammation, tissue edema and cystic degeneration of the glands in the early
      stage of polyp formation. Thus these neuropeptides may contribute to the
      development and growth of nasal polyps.

PMID- 7521110
TI  - [Volumetric correlations of prostatic adenoma by transrectal ultrasonography].
AB  - Estimation of prostate volume is one of the key elements in the study and
      management of both prostate benign diseases and prostate cancer. Of the available
      techniques, transrectal ultrasound presents greater reliability in prostatic
      imaging due to its degree of resolution. The present study conducted in 40
      patients undergoing suprapubic adenectomy piedes with the echographic dimensions
      and 14 different volumetric formulae obtained by the multiple combination of the
      three prostate axis. The two best correlations are obtained when the cross
      sectional measurement is combined with the anteroposterior (r = 0.84..0.83), and
      the worse when the longitudinal measure is used in isolation or combined with the
      anteroposterior one (r = 0.64..0.43). The exact formula is the ellipsoid
      [formula: see text] Contrary to what could be expected, the size of the "internal
      gland" (cross-sectional and anteroposterior) scarcely correlates to the adenoma
      weight, both with regard to the main axes (cross-sectional, r = 5.25;
      anteroposterior, r = 0.28) and the theoretical volume (r = 0.69).

PMID- 7521109
TI  - [Role of growth factors in the etiopathogenesis of benign prostatic hyperplasia].
AB  - A comment is made on the role growth factors play on the regulation of prostate
      growth. These factors require the mediation of an specific membrane receptor to
      which they have to bind in order to exercise their action correctly. The
      objective of the present job is to carry out a comprehensive review of each and
      every growth factor involved in prostate growth: family of the epidermal growth
      factor, family of the beta-transforming growth factor, and family of the
      fibroblast growth factor. As a final conclusion, it should be mentioned that the
      two prostate growth-regulating factors more extensively studied and with greater
      etiopathogenic relevance in benign prostate hyperplasia, are the epidermal growth
      factor and, more particularly, the fibroblast growth factor.

PMID- 7521111
TI  - [Controversies and progress in the diagnosis and treatment of benign prostatic
      hypertrophy. Personal experience].
AB  - Historically, non surgical procedures awakened little interest among urologists
      because surgery represented a definite solution with acceptable morbidity and
      mortality rates. Currently, the diagnosis and management of BPH is pointed
      towards a greater understanding of those prostate conditions with a trend to
      obstruction, using more refined methods to assess the severity of the
      obstruction, identification of predictive parameters of the therapeutical
      response, and evaluation of the various treatment alternatives based on safety
      and cost-efficiency parameters.

PMID- 7521112
TI  - [Endoscopic myocapsulotomy. Evaluation of the short-term clinical and urodynamic
      results].
AB  - Clinical and urodynamic evaluation of a series of 35 patients aged between 49 and
      85 years. Clinical symptoms presented post-miocapsulotomy reduction both in
      obstructive and irritative signs and symptoms in 97.2% and 91.6% cases,
      respectively. Likewise, a decrease in peak flow and peak flow percentile was
      shown in 80.5% and 80% of cases, respectively. Vesical instability was seen in
      90.9% and 55.5% of cases in pre- and post-operative studies respectively. An
      statistically significant post-operative drop (p < 0.05) in the detrusor's peak
      pressure during miction, (76.6 vs. 56 cm H2O), was confirmed. From our results it
      may be concluded that MC is a useful surgical technique in the treatment of
      prostatic obstruction, with the advantage versus other techniques that very
      frequently it preserves the proximal urinary continence mechanism and the sexual
      sphincter.

PMID- 7521113
TI  - [Prostatic carcinoma: healthy population screening or a better diagnosis?].
AB  - In the light of present knowledge with regard to prostate carcinoma, the concerns
      and objections that arise due to an eventual recommendation to the healthy
      population for systematic screening of prostate cancer are presented together
      with the possible identification of certain population groups which could benefit
      from it. It is concluded that in opposition to the concept of mass screening
      there is more logic today in the selective screening of risk groups and also that
      in future studies on the incidence on mortality figures these should be done on
      the country's own population. Up to the present time, the association of rectal
      examination and PSA is the best method available to establish a suspected
      diagnosis of prostate cancer.

PMID- 7521114
TI  - [Early diagnosis of prostatic cancer].
AB  - Prostate cancer is the most common neoplasia in males and, since it is curable
      only when detected in the early stages, it was estimated that screening would
      detect tumours in curable stages which would enhance the results in the fight
      against the disease. This, however, has not been elucidated since the condition's
      natural history in many cases unknown and it may be that unnecessary and
      iatrogenic overtreatment is being induced. The paper analyzes the various tests
      and diagnostic procedures available, primarily digital rectal examination, PSA
      determination, and transrectal ultrasound all used individually and in
      combination. Several unknown aspects await to be answered and many long-term
      studies continue to be necessary to explain whether early diagnosis of
      asymptomatic disease and subsequent treatment can improve life expectancy and
      quality of life as compared to plain treatment of symptomatic cases. We hope the
      answer will be available shortly and that we are "able to diagnose cancer in time
      but treat it only when we know it is required.

PMID- 7521115
TI  - Immunotherapeutic strategies directed at the trimolecular complex.

PMID- 7521116
TI  - The molecular basis of susceptibility to rheumatoid arthritis.

PMID- 7521119
TI  - Stenting of the ductus arteriosus in hypoplastic left heart syndrome as an
      ambulatory bridge to cardiac transplantation.

PMID- 7521117
TI  - Appearance of spermatozoon after administration of mast cell blocker to a patient
      with azoospermia.
AB  - Since a close relationship has been suggested to exist between testicular
      disfunction and the increased mast cells in the testis, we used a mast cell
      blocker for the treatment of patients with idiopathic infestility. An infertile
      male with idiopathic azoospermia was treated with administration of a mast cell
      blocker, tranilast for one year. The patient was found to have sperm within his
      ejaculate. However, the ultimate goal of pregnancy was not achieved by the
      microfertilization technique. To evaluate the possible significance of this new
      treatment, further basic research will be needed to clarify the relationship
      between mast cell proliferation and impaired testicular function.

PMID- 7521118
TI  - [Endocrine chemotherapy for prostatic cancer].
AB  - We carried out a randomized joint study on endocrine therapy and endocrine
      chemotherapy for prostatic cancer at our department and 17 affiliated
      institutions. Of 80 patients entered, 39 patients were treated with chlormadinone
      acetate alone (group A) and 41 patients were treated with chlormadinone acetate
      in combination with UFT (group B). After excluding 10 inappropriate patients,
      Stage C was observed in 14 patients in group A and 13 in group B, and stage D in
      20 patients in group A and 23 in group B. Side effects were observed in 8.8%
      (3/34) in group A and 22.2% (8/30) in group B without a significant difference.
      The anti-tumor effects (response rate) and clinical effects with respect to each
      item did not significantly differ between the two groups. The non-recurrence rate
      and survival rate were significantly higher in group B than in group A. These
      findings suggest the usefulness of endocrine chemotherapy using UFT.

PMID- 7521120
TI  - Chronic lymphocytic leukemia.

PMID- 7521122
TI  - Two Prader-Willi/Angelman syndrome loci present in an isodicentric marker
      chromosome.
AB  - We found an abnormal 47,XX,+mar karyotype in a patient with developmental delay,
      hypotonia, microcephaly, failure to thrive, and cognitive delay. When metaphases
      were hybridized with Prader-Willi and Angelman loci-specific probes by the FISH
      technique, two sites were noted at opposite positions on the marker chromosome.
      The alphoid satellite DNA probe documented the isodicentric nature while
      retention of the p arms on both sides of the marker chromosome was demonstrated
      by beta satellite probe. The patient does not exhibit manifestations of either
      syndrome despite the presence of these loci in tetrasomic dose. The present
      investigation suggests that other marker chromosomes be reevaluated, as their
      clinical manifestations are quite variable.

PMID- 7521121
TI  - GAPO syndrome in a child without dermal hyaline deposit.
AB  - A 5-year-old girl with GAPO syndrome from India lacked PAS-positive hyaline
      material in the skin biopsy from thigh and scalp. The role of this pathological
      change, earlier reported by Wajntal et al. [1990] in the pathogenesis of GAPO
      syndrome, needs to be reexamined.

PMID- 7521123
TI  - Six cases of 7p deletion: clinical, cytogenetic, and molecular studies.
AB  - To date, 32 cases of partial 7p monosomy have been described, 14 of which have
      been associated with craniosynostosis (CRS). There is considerable variation in
      the size and location of the deleted segment. However, CRS appears to be
      consistently associated with either a deletion or partial deletion 7p21-->7p22 or
      more rarely a deletion of 7p13-->7p14. Analysis of a panel of six 7p deletion
      cases (three with CRS) was undertaken using informative DNA probes, in order to
      characterize and define the extent of the deletions at the molecular level. There
      were five de novo deletions and one resulting from the unbalanced product of a
      paternal balanced insertion. The putative proximal CRS locus at 7p13-->7p14 does
      not appear to be allelic with Greig cephalopolysyndactyly syndrome. Three probe
      positions have been refined: pJ5.11 (D7S10) previously mapped to 7p14-->pter does
      not appear to map proximal to p15; TM102L (D7S135) does not map distal to p22;
      CRI-P137 (D7S65) maps distal to 7p13.

PMID- 7521126
TI  - Calcium channels in excitable cells: divergent genotypic and phenotypic
      expression of alpha 1-subunits.
AB  - The Ba2+ currents and mRNA levels of four members of the rat brain family of
      alpha 1-subunit Ca2+ channel genes were examined and compared in the rat cell
      lines GH3 and PC-12 and in the mouse lines NIE-115 and AtT-20. The RNA was
      measured with ribonuclease protection assays using probes derived from rat brain
      (rb) Ca2+ channel cDNAs (rbA, rbB, rbC, and rbD), and the Ba2+ currents were
      studied by whole cell patch-clamp recording. L-, N-, P-, and T-type currents were
      discriminated by the voltage dependence and pharmacological properties of Ba2+
      currents. All cell lines expressed all four rat brain Ca2+ channel genes, except
      GH3 cells, which lacked rbB. The functional diversity of Ba2+ currents, however,
      was quite different among the cell lines. GH3 cells showed evidence of L- and T
      type currents, undifferentiated PC-12 cells of L-type currents, AtT-20 cells of L
      , N-, and P-type currents, and undifferentiated NIE-115 cells of a T-type current
      that was partially blocked by both nifedipine and BAY K 8644. Dimethyl sulfoxide
      differentiated NIE-115 cells also had an L-type current. Differentiation of NIE
      115 cells caused an increase in the levels of rbB, rbC, and rbD RNAs.
      Differentiation by nerve growth factor caused an increase in levels of all four
      genes in PC-12. Our data give further support for the assignment of rbA, rbB, and
      rbC/rbD gene products as components of P-, N-, and L-type Ca2+ channels,
      respectively.

PMID- 7521124
TI  - Subcellular localization of CFTR to endosomes in a ductal epithelium.
AB  - Plasma membrane chloride transport by the cystic fibrosis transmembrane
      conductance regulator (CFTR) may be regulated by cellular processes that affect
      the cycling of CFTR with the plasma membrane. Testing this hypothesis requires
      cytochemical evidence for the presence of a subcellular compartment of CFTR. In
      this study, the subcellular distribution of CFTR in a normal epithelial cell
      population was characterized using immunofluorescence and immunoelectron
      microscopy. Two anti-CFTR antibodies, raised against different epitopes of the
      CFTR molecule, specifically labeled the apical pole of striated duct epithelial
      cells in tissue sections of rat submandibular gland. By use of electron
      microscopy, the CFTR immunoreactivity was associated with the apical plasma
      membrane and the membranes of many subapical vesicles. In this preparation, some
      of the CFTR-labeled vesicles were also labeled with antibodies against
      transferrin receptor and rab4, two markers of early endosomes and receptor
      mediated endocytosis. These observations provide direct cytochemical evidence for
      the existence of peripherally located CFTR-expressing endosomes and support the
      hypothesis that membrane recycling may contribute to CFTR function.

PMID- 7521127
TI  - Inhibition of acrosin by protein C inhibitor and localization of protein C
      inhibitor to spermatozoa.
AB  - Protein C inhibitor (PCI) is synthesized by cells throughout the male
      reproductive tract and is present in high concentrations (220 micrograms/ml) in
      seminal plasma. Seminal plasma as well as the acrosome of spermatozoa are rich in
      possible target proteases for PCI. We analyzed the interaction of PCI with
      acrosin, a serine protease stored in its zymogen form in the acrosome of
      spermatozoa. Purified human PCI inhibited the amidolytic activity of purified
      boar acrosin with an apparent second-order rate constant of 3.7 x 10(4) M-1.s-1.
      Inhibition was paralleled by the degradation of PCI from its 57- to its 54-kDa
      form. Human PCI also inhibited the amidolytic activity of activated human sperm
      extracts and formed complexes with acrosin as determined by an enzyme-linked
      immunosorbent assay. Immunocytochemistry revealed that morphologically abnormal
      spermatozoa stained for PCI antigen, whereas morphologically normal spermatozoa
      were negative. In immunoelectron microscopy, PCI was exclusively localized in the
      immediate vicinity of disrupted acrosomal membranes of sperm heads. These data
      suggest that PCI might function as a scavenger of prematurely activated acrosin,
      thereby protecting intact surrounding cells and seminal plasma proteins from
      possible proteolytic damage.

PMID- 7521125
TI  - Hepatocyte inducible nitric oxide synthesis is influenced in vitro by cell
      density.
AB  - Hepatocyte plating density is known to affect cell function. Human and rat
      hepatocytes have been shown to express the inducible nitric oxide synthase (INOS)
      in response to cytokines plus lipopolysaccharide (LPS). The following studies
      were performed to determine the effects of hepatocyte plating density on the
      regulation of INOS. Rat hepatocytes were plated at densities from 10(4) to 20 x
      10(4) hepatocytes/cm2 and stimulated with a combination of LPS, interferon-gamma,
      interleukin-1, and tumor necrosis factor. We found that NO2- plus NO3- released
      from stimulated hepatocytes declines with increasing hepatocyte density. Similar
      effects were seen for 3',5'-cyclic monophosphate release into supernatants and in
      the amount of nonheme iron-nitrosyl signals measured by electron paramagnetic
      resonance spectroscopy. Limitations of substrate (L-arginine) and 5,6,7,8
      tetrahydrobiopterin were excluded as cause of the reduced nitric oxide generation
      at higher densities. Although mRNA levels for INOS were not influenced when
      measured at 24 h, there was a marked reduction in INOS enzyme activity and INOS
      protein detectable by Western blotting at higher cell density. Total protein
      synthesis decreased as hepatocyte density increased in both nonstimulated and
      stimulated hepatocytes at higher cell densities. These data suggest that reduced
      INOS translation may account for the density-dependent reduction in INOS activity
      in cultured hepatocytes. The importance of this phenomenon remains to be
      determined in vivo but has important implications for the in vitro study of INOS
      expression.

PMID- 7521128
TI  - Coupled secretion of chloride and mucus in skin of Xenopus laevis: possible role
      for CFTR.
AB  - We used the isolated skin of Xenopus laevis to investigate the relationship
      between the secretion of salt, water, and mucus by submucosal glands expressing
      the cystic fibrosis transmembrane conductance regulator (CFTR). In situ
      hybridization and immunofluorescence provided evidence for specific expression of
      CFTR in the mucus-secreting cells of the subepidermal glands. Stimulation of
      isolated sheets of skin with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic
      monophosphate produced active Cl secretion and a marked increase in tissue
      conductance that was correlated with mucous cell degranulation and the distention
      of the glandular ducts. This coordinated increase in active secretion of salt and
      mucus was abolished by pretreatment of skins with bumetanide or by removing Cl
      from the bathing solutions. These results provide evidence for an intimate
      coupling between electrolyte transport and mucus secretion that may illuminate
      the pathophysiology of mucus-producing glands in cystic fibrosis lung disease.

PMID- 7521132
TI  - Delayed activation of single mechanosensitive channels in Lymnaea neurons.
AB  - Some stretch-activated (SA) channels challenged with suction jumps exhibit
      adaptation, a dynamic behavior that can be overlooked because of its mechanical
      fragility. In previous studies of neuronal SA K channels, we detected no
      adaptation, but the protocols used were not designed to detect dynamics. Here, we
      reproduce the adaptation seen by others in Xenopus SA cationic (Cat) channels but
      show that, with the same protocol, no adaptation occurs with SA K channels.
      Instead, SA K channels exhibit a different dynamic behavior, delayed activation.
      Lymnaea SA K channels subjected to pressure jumps responded after a 1- to 4-s
      delay with a gradual, rather than abrupt, onset of activation. The delay was
      pressure dependent and was longer for patches from older cultured neurons.
      Delayed responses were fragile like SA Cat channel adaptation; they disappeared
      with repeated stimuli. Cytochalasin D decreased the delay and increased the
      stretch activation of SA K channels. Unlike SA Cat channel adaptation, which
      occurs only at hyperpolarized potentials, SA K channel delay was not voltage
      dependent. We note that once SA Cat and SA K channels are "stripped" of their
      fragile (cytoskeleton-dependent?) dynamics, however, their gating behaviors show
      little fundamental difference; both are stretch activatable and have a higher
      open probability at depolarized potentials.

PMID- 7521129
TI  - Voltage-dependent ionic conductances in Chinese hamster ovary cells.
AB  - Chinese hamster ovary (CHO) cells are becoming a widely used biological material.
      A number of studies report membrane ion conductance changes after transfection of
      channels and receptors, but there are few data available on the properties of
      membrane ion conductances of CHO cells before transfection. In this work we
      studied voltage-dependent ionic conductances in cultures of CHO native (CHO-K1)
      cells. Three types of voltage-dependent ionic conductances were identified: 1) a
      K+ conductance showing sensitivity to Ca2+ and a unit conductance of
      approximately 210 pS in symmetrical 150 mM K+ outside-out patches (this
      conductance, which did not inactivate during a 160-ms pulse, was inhibited by 30
      nM charybdotoxin but not by 30 mM extracellular tetraethylammonium); 2) a rapidly
      activating and inactivating tetrodotoxin (TTX)-sensitive inward current, peaking
      at about -10 to 0 mV (this current showed characteristics similar in many
      respects to Na+ current recorded in neurons); and 3) another voltage-dependent
      inward current, which had slow inactivation, was TTX insensitive but was blocked
      by Co2+ (current was also carried by Ba2+, peaked at approximately 0 to +10 mV,
      was identified as a Ca2+ conductance, and was inhibited by dihydropyridines but
      not by 10 microM omega-conotoxin). Cell-attached patch recordings of single Ca2+
      channel currents demonstrated a unitary conductance of approximately 20 pS.

PMID- 7521131
TI  - Characterization of gap junctions between pairs of Leydig cells from mouse
      testis.
AB  - Leydig cells are coupled in vivo by numerous gap junctions. In vivo and in vitro
      cells were immunolabeled by connexin 43 (Cx43) but not by Cx26 or Cx32
      antibodies; immunoblotting confirmed specificity of Cx43 labeling. Pairs of
      Leydig cells dissociated from mouse testis were studied by dual whole cell
      voltage clamp, and a high incidence of dye (n = 20) and electrical coupling (n =
      60; > 90%) was found. Coupling coefficients were near 1 and junctional
      conductance (gj) averaged 7.2 +/- 1.2 nS (SE, n = 40). Large transjunctional
      voltage (Vj) decreased gj; currents decayed exponentially with time constants of
      seconds that decreased at greater Vj. The residual conductance at large Vj was at
      least approximately 40% of the initial conductance. Exposure of cell pairs to
      saline solutions saturated with CO2 (n = 15) or containing 2 mM halothane (n =
      15) or 3.5 mM heptanol (n = 15) rapidly and reversibly reduced gj. In eight cell
      pairs, gating of single junctional channels was observed during halothane-induced
      reduction in gj. Most gating events at Vj < 40 mV were fit by a Gaussian
      distribution with a mean of approximately 100 pS. With Vj > 40 mV, smaller
      transitions of approximately 30 pS were also recorded, and the frequency and
      duration of the approximately 100-pS transitions decreased. Also, approximately
      70-pS transitions between 30- and 100-pS conductances were observed in the
      absence of 70-pS transitions to or from the baseline, indicating that the 30-pS
      conductance was a substate induced by large Vj.

PMID- 7521130
TI  - Early effects of PRL on ion conductances in CHO cells expressing PRL receptor.
AB  - Chinese hamster ovary (CHO-K1) cells were stably transfected with prolactin (PRL)
      receptor cDNA. These cells (CHO-E32) expressed the long form of functional PRL
      receptor. Using microfluorimetric and patch-clamp techniques, we have
      investigated the effects of PRL on intracellular Ca2+ concentration ([Ca2+]i) and
      membrane ion conductances. Exposure of CHO-E32 cells to 5 nM PRL resulted in an
      increase in [Ca2+]i. Two types of response were observed: 1) a stimulation of
      Ca2+ entry and 2) an intracellular Ca2+ mobilization. As PRL inhibited voltage
      activated Ca2+ current, the PRL-induced Ca2+ increase does not involve voltage
      activated Ca2+ channels. PRL also increased a charybdotoxin-sensitive Ca(2+)
      dependent K+ conductance. Simultaneous measurements showed that PRL
      hyperpolarized the membrane potential before increasing intracellular Ca2+
      levels. In voltage clamp, hyperpolarizing voltage steps were associated with
      increased Ca2+ concentrations, whereas depolarizing voltage steps decreased
      [Ca2+]i. Cell-free patch-clamp experiments showed that PRL directly stimulates K+
      channel activity. Our results suggest the existence of a regulatory complex
      involving a protein kinase tightly associated with the Ca(2+)-activated K+
      channels and that PRL stimulates these channels by means of the activation of
      protein kinase. The resulting hyperpolarization stimulates Ca2+ entry, probably
      through voltage-insensitive nonspecific channels.

PMID- 7521133
TI  - Growth hormone and parathyroid hormone stimulate IGFBP-3 in rat osteoblasts.
AB  - Osteoblast-like cells prepared from calvaria of newborn rats produce insulin-like
      growth factor (IGF) I and several insulin-like growth factor binding proteins
      (IGFBPs) in vitro. Among the IGFBPs found in conditioned cell culture medium,
      IGFBP-3 is the most abundant. Intact IGFBP-3, as assessed by 125I-labeled IGF-II
      ligand blot analysis, is more abundant in culture media of cells exposed to
      growth hormone (GH) or to parathyroid hormone (PTH), both at 5 x 10(-9) mol/l,
      for 24 h. At the same time, concentrations of IGF-I are increased in media of
      cells exposed to PTH but not to GH, compared with hormone-free control cultures.
      IGFBP-3 mRNA is increased in osteoblasts exposed to PTH or to GH but not in
      response to 5 x 10(-9) mol/l IGF-I. PTH exerts a rapid (within 2 h) stimulatory
      effect on IGF-I and IGFBP-3 production, both at the message and peptide levels,
      whereas GH increases only IGFBP-3, both at the message and peptide levels (after
      24 h). We conclude that IGF-I does not mediate increased IGFBP-3 production by
      rat osteoblasts in response to GH and PTH.

PMID- 7521134
TI  - Activin A: negative regulator of amylase secretion and cell proliferation in rat
      pancreatic acinar AR42J cells.
AB  - Activin A, a member of the transforming growth factor-beta supergene family,
      exists in secretory granules of non-B-cells of rat pancreatic islet (H. Yasuda,
      K. Inoue, H. Shibata, T. Takeuchi, Y. Eto, Y. Hasegawa, N. Sekine, Y. Totsuka, T.
      Mine, E. Ogata, and I. Kojima. Endocrinology 133: 624-630, 1993). Because
      functions of exocrine pancreas are influenced by hormones in pancreatic islet, it
      is possible that activin A affects the function of pancreatic acinar cells. To
      examine this possibility, we studied the effects of activin A on amylase
      secretion and DNA synthesis in AR42J cells. In these cells, dexamethasone (Dx)
      induces increases in secretory organelles and secretion of amylase (C. D.
      Logsdon, J. Moessner, J. A. Williams, and I. D. Goldfine. J. Cell Biol. 100: 1200
      1208 1985). Activin A did not change the rate of amylase release by itself nor
      affect the cholecystokinin-stimulated amylase release from Dx-treated
      differentiated AR42J cells. However, when activin A was added together with Dx,
      activin A inhibited Dx-induced increase in amylase content in a dose-dependent
      manner. In the presence of 1 nM activin A, the effect of Dx was abolished. In the
      absence of Dx, amylase content of the cells was also reduced by activin A in a
      dose-dependent manner. The maximum inhibitory effect was obtained by 10 nM
      activin A, and at this concentration amylase content became undetectable. In
      addition, activin A potently inhibited DNA synthesis as assessed by [3H]thymidine
      incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521135
TI  - Distribution of nitric oxide synthase activity in arterioles and venules of rat
      and human intestine.
AB  - NO is produced within peripheral blood vessels through the action of the
      differentially distributed constitutive and inducible NO synthase isoforms in the
      vessel wall. As in other sites in the periphery, NO exerts local vasodilatory
      actions in the gastrointestinal microvasculature and is proposed to play a role
      in enteric vasomotor regulation. Using NO synthase histochemistry and endothelial
      cell immunohistochemistry, we provide the first anatomic evidence of NO synthesis
      in both endothelial and smooth muscle cells of submucosal blood vessels in the
      rat and human intestine. The findings of this study indicate that 1) as in the
      periphery, both the endothelial and vascular smooth muscle cells of the
      microvessels irrigating the rat and human intestinal wall possess NO synthesis
      potential, 2) NO synthase activity is predominantly localized to discrete
      subcellular patches, and 3) the source of NO within the vascular wall, either
      intimal or medial, should be a consideration in future studies in terms of the
      relative contribution of these sources of vasomotor tone in the rat and human gut
      wall.

PMID- 7521136
TI  - A volume-activated taurine channel in skate hepatocytes: membrane polarity and
      role of intracellular ATP.
AB  - Osmoregulation in isolated hepatocytes and perfused livers of the little skate
      (Raja erinacea), an osmoconforming marine elasmobranch, is mediated in part by
      the uptake or release of the intracellular osmolyte taurine. To further
      characterize the efflux mechanism, [14C]taurine release and Na(+)-independent
      uptake were assessed after cell swelling in hypotonic media containing 0.1-100 mM
      taurine. Rate coefficients for [14C]taurine uptake (0.016 +/- 0.002 min-1) and
      efflux (0.015 +/- 0.003 min-1) were similar and independent of extracellular
      taurine concentration, indicating that a taurine-permeable channel mediates the
      release of this amino acid after cell swelling. Volume-activated taurine uptake
      and efflux were both blocked by pretreatment with the metabolic inhibitors 2,4
      dinitrophenol, antimycin A, and KCN plus iodoacetate, by the sulfhydryl-reactive
      compound N-ethylmaleimide and the transport inhibitor 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid. [14C]taurine release via this
      channel was immediately blocked if isotonicity was restored or a membrane
      permeable metabolic inhibitor (0.5 mM 2,4-dinitrophenol) was added at different
      times after a hypotonic stimulus. Similar, although delayed, effects were noted
      with antimycin A and KCN plus iodoacetate. When isolated perfused skate livers
      were exposed to hypotonic stimuli, all of the taurine was released into the
      sinusoidal circulation, but not into bile, an effect that was also blocked by
      restoring isotonicity. These findings demonstrate that taurine efflux from skate
      hepatocytes after cell swelling is mediated by a channel. This channel is
      localized to the basolateral membrane and appears to require the continual
      presence of intracellular ATP for its function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521137
TI  - Differential expression of substance P, somatostatin, and VIP in neurons from
      cultured myenteric ganglia.
AB  - The expression of three enteric neuropeptides was examined in freshly dispersed
      ganglia and in ganglia cultured for up to 28 days. During culture, glial cells
      grew into a flat sheet surrounding a cluster of neurons identified with neuron
      specific enolase (13 +/- 2/ganglion), which remained constant throughout the
      period of culture. The neurons underwent a distinctive temporal change, resulting
      in overexpression of substance P (SP), normal expression of somatostatin, and
      virtual suppression of vasoactive intestinal peptide (VIP). Three weeks after the
      start of culture, the ganglia contained and released (in response to 55 nM KCl,
      0.1 mM 1,1-dimethyl-4-phenylpiperazinium, or 1 microM gastrin-releasing peptide)
      twice as much SP as freshly dispersed ganglia, corresponding to a sevenfold
      increase per cultured neuron; content and release of somatostatin did not change.
      SP content and release declined to 1.5% of those found in control cultures when
      nonneuronal cells were suppressed with cytosine arabinoside but were partially
      restored (13-17% of control) by nerve growth factor. In marked contrast, VIP was
      minimally (< 1%) present in and released from ganglia after the third day in
      culture. Suppression of VIP could reflect a selective loss of VIP neurons and/or
      VIP expression.

PMID- 7521138
TI  - Phorbol-stimulated influx of extracellular calcium in rat pulmonary artery
      endothelial cells.
AB  - Stimulation of rat pulmonary artery endothelial cells (RPAEC) with phorbol 12
      myristate 13-acetate (PMA) resulted in an increase in intracellular calcium
      ([Ca2+]i). Unlike the response to bradykinin, C5a and tumor necrosis factor-alpha
      (TNF-alpha) previously reported (15), the PMA-induced increase in [Ca2+]i was
      predominantly dependent on extracellular calcium. The PMA response paralleled the
      BAY K 8644-induced, extracellular calcium-dependent increase in [Ca2+]i.
      Pretreatment of endothelial cells with the protein kinase C inhibitor
      staurosporine resulted in a concentration-dependent inhibition of the increase in
      [Ca2+]i in response to PMA. The ability of PMA analogues to induce significant
      increase in [Ca2+]i paralleled their ability to induce O2- generation in
      neutrophils. The PMA-induced influx of extracellular Ca2+ was inhibited by the L
      channel selective antagonists diltiazem, nifedipine, nicardipine, and verapamil
      in a dose-dependent manner. Depolarizing conditions induced by high [K+]o
      enhanced the calcium response to PMA. The data presented are consistent with the
      hypothesis that PMA-induced increases in [Ca2+]i in endothelial cells are the
      result of Ca2+ influx through voltage-dependent L-type Ca2+ channels.

PMID- 7521139
TI  - Chloride secretion and function of serous and mucous cells of human airway
      glands.
AB  - Cells from the acini of human tracheal glands were grown in culture to produce
      confluent cell sheets of mucous or mixed seromucous phenotype. Levels of mediator
      induced Cl secretion in mucous cells were 2-18% those of seromucous cells. Levels
      of the cystic fibrosis transmembrane conductance regulator (an apical membrane Cl
      channel) were also much less in mucous than in seromucous cells. These results
      suggest that serous cells are more important than mucous cells in providing the
      fluid component of gland secretions.

PMID- 7521140
TI  - Sulfated glycoconjugates as disrupters of Plasmodium falciparum erythrocyte
      rosettes.
AB  - Some strains of Plasmodium falciparum form erythrocyte rosettes that are believed
      to result from a lectin interaction between malaria-infected and uninfected
      erythrocytes. The sulfated glycoconjugate heparin and certain heparin derivatives
      have been observed to disrupt rosettes. To investigate this interaction further,
      we have studied the effects of four sulfated glycoconjugates on 15 fresh isolates
      of P. falciparum from Papua New Guinea. A broader range of sulfated
      glycoconjugates has been tested against a laboratory strain. A concentration of
      1,000 micrograms/ml of dextran sulfate (molecular weight [MW] 500,000) was the
      most potent disrupter of rosettes. Fucoidan, heparin, and dextran sulfate (MW
      5,000) were of decreasing effectiveness in 14 of 15 fresh isolates. The same
      relationship was true for the laboratory strain. Pentosan polysulfate and
      sulfatide also disrupted rosettes; chondroitin sulfates A, B, and C and keratan
      sulfate gave either minimal or no rosette disruption. Thus, some sulfated
      glycoconjugates are potent disrupters of P. falciparum erythrocyte rosettes.
      Sulfated glycoconjugates that are potent disrupters of P. falciparum rosettes may
      prove useful in identifying ligands involved in rosette formation.

PMID- 7521142
TI  - Population analysis of cellular responses to synthetic peptides of Der p II, a
      major allergen molecule of Dermatophagoides pteronyssinus, in allergic and
      nonallergic subjects.
AB  - Responses of peripheral blood mononuclear cells to synthetic oligopeptides of Der
      p II, one of the major allergen molecules of Dermatophagoides pteronyssinus, were
      compared between allergic and nonallergic subjects. Healthy subjects showed
      positive responses to crude extracts of D. pteronyssinus, but only allergic
      subjects showed elevated cellular responses to Der p II. We synthesized three
      oligopeptides of Der p II in which motifs of a possible T-cell epitope were
      included. Of 14 subjects with positive response to Der p II, three responded to
      all three peptides, while five did not respond to any peptide tested. In 11
      allergic patients who showed positive response to Der p II, responsiveness to the
      peptide K33-T47 was significantly higher than that to other peptides (P < 0.05).
      All the responding patients were also positive for scratch test to Der p II,
      suggesting that those epitopes induced IgE-promoting helper T-cell response in
      allergic persons. On the other hand, the in vitro cellular responses were not
      necessarily correlated to IgE production against Der p II in healthy subjects.

PMID- 7521141
TI  - Immune responses to nematode exoantigens: sensitizing antibodies and basophil
      histamine release.
AB  - High levels of IgE and eosinophilia are found in both allergy and helminth
      infections, but allergic symptoms are rare in naturally acquired helminth
      infections. The interrelation of specific IgE antibodies and in vitro basophil
      histamine release (HR) induced by exoantigens from the larval stages (L2/L3) of
      the nematodes Toxocara canis and Ascaris suum was examined in 148 patients
      visiting an outpatient clinic for parasitic diseases. The antigen sensitivity of
      the basophils was found to be dependent not only on the absolute amount of
      antigen-specific IgE present in patient plasma, but also on the ratio between
      specific and total IgE. Thus, large HR was observed in some patients in response
      to helminth antigens despite low levels of both specific and total IgE content in
      plasma. Patients with eosinophilia showed greater IgE-mediated HR than the other
      patients examined. In contrast, only five patients showed HR after challenge with
      anti-IgG4, despite the presence of high levels of antigen-specific IgG4 and IgG1
      in all patients showing specific IgE antibodies.

PMID- 7521143
TI  - Surimi and native codfish contain a common allergen identified as a 63-kDa
      protein.
AB  - We have compared the allergenicity of codfish and surimi (prepared from codfish)
      by skin testing, specific IgE-RIA, and leukocyte histamine release (LHR) in six
      fish-allergic patients. Prick tests were positive for codfish and, to a lesser
      extent, surimi. The percentages of labeled anti-IgE bound to surimi-Sepharose
      were 1.55 +/- 0.19% and 3-6% with control and patient sera, respectively.
      Inhibition of the surimi protein-Sepharose IgE-RIA was greatest (80%) at protein
      concentrations of 13.4 and 408.5 micrograms/ml for codfish and surimi extract,
      respectively. The allergenic protein was isolated by gel filtration and subjected
      to SDS-PAGE. The eluate from codfish contained several proteins ranging from 13
      to 63 kDa, while the eluate from surimi contained a single 63-kDa protein. It was
      concluded that surimi contained a single allergenic protein.

PMID- 7521145
TI  - Electrochemically active DNA probes: detection of target DNA sequences at
      femtomole level by high-performance liquid chromatography with electrochemical
      detection.
AB  - Electrochemically active DNA probes were prepared by linking a ferrocene unit
      with 5'-aminohexyl-terminated oligonucleotides. The DNA sequences of probes 5a,
      5b, and 5c were 5'-T12-3', 5'-T20-3', and 5'-TGCAG TTCCG GTGGC TGATC-3',
      respectively. Probe 5a could form a complex selectively with a single-strand
      poly(A) and a double-strand DNA fragment containing an A13 sequence and these
      complexes could be detected at femtomole levels by an electrochemical detector
      (ECD) on HPLC. The observed ECD response was proportional to the amount of the
      complex over the range 20-100 fmol. Probe 5c was capable of detecting femtomole
      levels of a restriction DNA fragment having oncogene v-myc. Moreover, probe 5b
      was able to detect picogram levels of mRNA taken from rat brain or yeast total
      cellular RNA. This proves that the electrochemically active DNA probes are useful
      in analyzing traces of DNA and RNA carrying the complementary sequence.

PMID- 7521146
TI  - Staining of immunoblots by immunochromatography.

PMID- 7521149
TI  - The relationship of angiogenesis to biological activity in human squamous cell
      carcinomas of the head and neck.
AB  - Tumor angiogenesis has recently been related to tumor growth and metastasis,
      which determine the clinical outcome of the patient. This study was designed to
      determine the relationship between angiogenesis in primary squamous cell
      carcinomas (SCC) of the head and neck and the development of recurrent or
      metastatic disease, or both. Different SCC of the head and neck were studied.
      Microvessels were selectively stained using a monoclonal antibody for factor
      VIII. Microvessel counts were performed in the tumor, in the tissues immediately
      adjacent, and in normal tissues of similar topographies. Microvessel counts were
      then correlated with clinical outcome (development of recurrent or metastatic
      disease, or both). Recurrent or metastatic disease, or both, developed in
      patients with high microvessel counts (mean, 121.25) in the tissues adjacent to
      the tumor 7 to 16 months after initial treatment. Those with low microvessel
      counts (mean, 33.75) were disease-free for 16 months to 6 years (p < 0.01).
      Microvessel counts inside the tumor were also higher in those in whom recurrences
      or metastasis, or both, developed, but were not statistically significant. In
      this study, angiogenesis was directly related to clinical outcome. Thus,
      angiogenesis may be an independent predictor of recurrent or metastatic disease,
      or both, which could help in the selection of patients with SCC of the head and
      neck for aggressive therapy.

PMID- 7521144
TI  - A modified nonradioactive method for northern blot analysis.
AB  - In this report we use several previously described methods, in novel combination,
      to establish a sensitive and flexible nonradioactive method. First, we prepared
      single-stranded digoxigenin-labeled probes using a high-efficiency polymerase
      chain reaction (PCR) method (4). For detection of RNA, blots were hybridized with
      probes containing digoxigenin and then incubated with alkaline phosphatase
      conjugated anti-digoxigenin antibody. Bound probe was rapidly detected with X-ray
      film using localized light emission from the reaction of alkaline phosphatase
      with lumigen-paraphenylenediamine substrate (5). This method allows flexibility
      in probe sequence selection, independent of restriction enzyme site location, and
      it works well with small probes. This approach allows sensitive differential
      analysis of closely related members of a gene family.

PMID- 7521147
TI  - Isolation of intact DNA and RNA from plant tissues.

PMID- 7521150
TI  - [Action of naftidrofuryl in cerebral neovascularization after cortical lesion in
      rats].
AB  - In this study, naftidrofuryl's action on vascular network regeneration is
      evaluated after cortical lesion produced by suction. The vascular reaction was
      analyzed in the region of the damaged cortex and the corresponding contralateral
      cortex. Comparison of results by variance analysis confirms that the effect of
      treatment is highly significant (p = 0.008). The results thus obtained show that
      post-lesion angiogenesis is facilitated and that capacities of post-lesion
      cerebral function regeneration could also be improved.

PMID- 7521148
TI  - Origin and peptide content of nerve fibers in the nasal mucosa of rats.
AB  - Injection of the retrograde neuronal tracer True blue into the anterior-lateral
      part of the nasal mucosa of rats labeled nerve cell bodies in the superior
      cervical ganglion, the sphenopalatine ganglion, the otic ganglion and the
      trigeminal ganglion on the ipsilateral side. In the superior cervical ganglion,
      the sphenopalatine ganglion and the trigeminal ganglion on the contralateral
      side, very few nerve cell bodies were labeled, indicating that these ganglia
      provide minor contributions only. The number of labeled cell bodies indicates
      that the superior cervical ganglion, the sphenopalatine ganglion and the
      trigeminal ganglion contribute most to the innervation of the nose, while the
      contribution from the otic ganglion is minor. Cell bodies in the superior
      cervical ganglion harbored noradrenaline (NA) or NA/neuropeptide Y (NPY); in the
      sphenopalatine ganglion vasoactive intestinal peptide (VIP) or VIP/NPY; in the
      otic ganglion VIP, VIP/NPY or VIP/substance P (SP) and in the trigeminal ganglion
      calcitonin gene-related peptide (CGRP) or CGRP/SP. The results from denervations
      and tracer experiments suggest that all NA-containing and the majority of NPY
      containing fibers in the nasal mucosa are derived from the superior cervical
      ganglion (sympathetic nerve supply). VIP- and VIP/NPY-containing fibers originate
      from the sphenopalatine and optic ganglia (parasympathetic nerve supply). Nerve
      fibers containing CGRP and CGRP/SP emanate from the trigeminal ganglion (sensory
      nerve supply).

PMID- 7521151
TI  - Interferon entry through the blood-brain barrier in glioma and its effect on
      lipoxygenase activity.
AB  - This study evaluates cerebral entry of mouse interferon alpha/beta (MuIFN
      alpha/beta) or mouse interferon gamma (MuIFN-gamma) following continuous (3 day),
      subcutaneous infusion of normal or glioma bearing mice. The intracerebral C57BL/6
      mouse glioma-26 (G-26) model was used at days 10-14 post tumor implant, the
      advanced stage of glioma progression as defined by histology and the median
      survival time (27 +/- 3.8 days). The infusion of horseradish peroxidase (HRP) in
      vivo at day 10 or 11 post glioma implant showed strong staining in the tumor bed
      indicating compromised blood-brain barrier (BBB). In addition, histochemistry
      with Bandeiraea simplicifolia isolectin B4 demonstrated the accumulation and/or
      activation of macrophage/microglia. The 3 day infusion of mice (day 11-14 post
      tumor implant) via subcutaneous (sc) osmotic micro-pumps with MuIFN alpha/beta
      (8x10(5) - 1.7x10(6) international units [IU]/ml) or with recombinant mouse
      interferon gamma (rMuIFN-gamma) (1x10(6) IU/ml) resulted in a low but detectable
      (1-5 IU/ml) cerebral level of IFN. The IFN levels in the blood (20-40 IU/ml) and
      brain, measured by assay of inhibition of viral cytopathic effect (CPE) or ELISA
      assay for MuIFN-gamma, showed no difference between normal and glioma bearing
      mice. The lipoxygenase (LO) activity (dioxygenase) of glioma tissue and
      contralateral control was evaluated in non-treated and MuIFN alpha/beta
      continuously (3 day) treated mice. The LO activity in glioma tissue was
      significantly higher (p < 0.05) than the contralateral control in non-treated
      mice. However, following sc MuIFN alpha/beta infusion the LO activity of glioma
      decreased to control level.

PMID- 7521152
TI  - Effect of cytokines on the proliferation and differentiation of acute
      promyelocytic leukemia cells: possible relationship to the development of
      "retinoic acid syndrome".
AB  - The effect of cytokines on the proliferation and differentiation of leukemia
      cells from 5 patients with acute promyelocytic leukemia (APL) was examined.
      Interleukin-1 beta (IL-1), interleukin-3 (IL-3), granulocyte-macrophage colony
      stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF)
      augmented uptake of 3H-thymidine into the DNA of APL cells in a dose-dependent
      manner in all cases. This stimulatory effect was pronounced in some, but not all,
      cells treated with all-trans retinoic acid (ATRA). However, nitroblue tetrazolium
      reducing activity was induced in a concentration-dependent manner by ATRA in all
      cases. The cytokines greatly enhanced NBT reduction of APL cells treated with
      ATRA, and a mixture of cytokines was more effective than a single cytokine.
      Although GM-CSF, IL-3 and IL-1 significantly modulated the ATRA-induced
      morphological changes, they did not induce CD14 expression, a typical marker of
      monocytic differentiation. In the presence of ATRA, GM-CSF potentiated production
      and secretion of tumor necrosis factor-alpha (TNF) in response to
      lipopolysaccharide, as well as interferon-gamma which is a potent inducer of
      monocytic differentiation in APL cells. On the other hand, production of TNF in
      ATRA-treated cells was not affected by G-CSF which significantly enhanced
      granulocytic differentiation. The effect of cytokines on APL cell differentiation
      should be considered in ATRA treatment for APL patients. Potentiation of cytokine
      production in APL cells associated with myelomonocytic differentiation is
      noteworthy in the pathogenesis of "retinoic acid syndrome".

PMID- 7521153
TI  - Clear cell carcinoma of salivary glands: immunohistochemical evaluation of clear
      tumor cells.
AB  - A total of 14 cases of clear cell carcinoma of salivary glands were evaluated by
      immunohistochemical methods using monoclonal antibodies to cytokeratin (K1.1 and
      K8.12), vimentin, S-100 alpha and beta subunits, neuron-specific enolase (NSE),
      glial fibrillary acidic protein (GFAP), MAM-3 and MAM-6 antigens and
      proliferating cell nuclear antigen (PCNA), as well as polyclonal antibodies to
      lysozyme (Ly), lactoferrin (la) and Alpha-1-antichymotrypsin (alpha 1-Ach).
      Histopathologically, the carcinoma was characterized by round or polygonal tumor
      cells with cytoplasm that does not stain with hematoxylin and eosin, nuclei with
      little pleomorphism and few or no mitotic figures, and growing in solid sheets,
      small nests or cords with collagenous stroma. Cytokeratin KL1 and K8.12 was
      present in few tumor cells with almost negligible to strong reaction in all
      cases, vimentin in 6, GFAP in 5 cases with multiple-expression of cytokeratin
      K8.12, vimentin and GFAP in 5 cases. S-100 protein immunoreactivity was the most
      prominent feature with more intense reaction of S-100 beta than S-100 alpha
      subunit. NSE reactivity was seen in 6 cases. Ly, La, a1-ch, MAM-3 and MAM-6
      antigens were localized in clear cells with various reaction intensities. The
      authors conclude that the clear tumor cells in clear cell carcinoma of salivary
      glands are not myoepithelial in origin but epithelial or neuroectodermal/neural
      crest in origin, showing ductal differentiation at the immunohistochemical level.

PMID- 7521154
TI  - Enhanced cytotoxicity caused by increased DNA strand breakage resulting from
      synergistic potentiation of bleomycin with Bacillus thuringiensis subsp.
      israelensis delta-endotoxin.
AB  - We previously reported that a 25 kDa Bacillus thuringiensis subsp. israelensis
      (BTI) delta-endotoxin potentiates the cytotoxicity of bleomycin (BLM) in cultured
      cells. In order to clarify the mechanism involved, we examined the induction of
      DNA strand breakage by BLM in the presence of BTI toxin. Results showed that the
      increase in strand breakage resulted in enhanced cytotoxicity through the
      synergistic potentiation of BLM with BTI toxin.

PMID- 7521155
TI  - Acquisition of resistance to 6-azauridine through DNA amplification in neoplastic
      but not normal osteoblasts.
AB  - In this communication, we have characterized the resistance to AZUrd in
      tumorigenic mouse C3H-OS osteosarcoma cells and non-tumorigenic MC3T3-E1
      osteoblast cells. DNA and RNA blot analysis showed a 30-fold increase in UMP
      synthase specific DNA and a 10-fold increase in mRNA, respectively, in resistant
      versus non-resistant C3H-OS cells. No corresponding increases in either UMP
      synthetase DNA or mRNA were evident in resistant MC3T3-E1 osteoblasts. Karyotype
      analysis of MC3T3-E1 and C3H-OS cells revealed translocations in the resistant
      cells. Regardless of drug-sensitive or resistant phenotype, the normal and
      neoplastic cells exhibited aneuploidy which was significantly more pronounced in
      the non-resistant tumor cells. Additionally, the number of chromosomes decreased
      in all resistant cells whether normal or neoplastic. We conclude that genomic
      instability in neoplastic cells is a prerequisite for the generation of drug
      resistant variants via the process of gene amplification.

PMID- 7521157
TI  - Genetic diversity of Datisca cannabina-compatible Frankia strains as determined
      by sequence analysis of the PCR-amplified 16S rRNA gene.
AB  - The presence of Frankia strains in soil samples collected from northern areas of
      Pakistan was detected by inoculating Coriaria nepalensis and Datisca cannabina
      plants. The abundance of compatible Frankia strains in some areas was indicated
      by profuse nodulation of the host plants, whereas soil samples from other
      localities failed to result in nodulation. An oligonucleotide probe (COR/DAT)
      directed against the 16S rRNA gene of the endophytes of Coriaria and Datisca spp.
      that did not cross-react with the RNA gene of Frankia strains isolated from other
      hosts was developed. Genetic diversity among Frankia strains nodulating D.
      cannabina was determined by sequence analysis of the partial 16S rRNA gene
      amplified from nodules induced by soil samples from different localities by PCR.
      Four types of Frankia sequences and one non-Frankia sequence were detected by
      hybridization with a Frankia genus probe and the COR/DAT probe as well as by
      sequence analysis of the cloned PCR products.

PMID- 7521156
TI  - Maintenance of human benign prostatic hyperplasia tissues in the nude mouse.
AB  - Human benign hyperplastic prostate (BHP) tissues were implanted subcutaneously in
      male Beige nude mice for up to 16 weeks. The implants maintained the normal
      histological appearance of BPH without signs of atrophy for up to 6 weeks. Their
      epithelium expressed proliferating cell nuclear antigen (PCNA), demonstrating
      that these cells actively underwent cell division. Thereafter the tissues
      gradually became atrophic, and some tissues maintained for 16 weeks completely
      lost recognizable prostatic epithelium. The glandular epithelium tended to
      undergo squamous cell metaplasia associated with atrophy. The epithelial linings
      of the implants consistently expressed prostate-specific antigen and prostate
      acid phosphatase as demonstrated by immunohistochemistry, except in areas of
      severe atrophy and squamous metaplasia. The nuclei of the implants hybridized
      with a human-specific DNA probe. Continuous feeding of the mice with
      dihydrotestosterone or hydrocortisone did not change significantly the morphology
      or the proliferation index of the epithelial cells within the glandular alveoli
      of implanted tissues or of normal mouse prostates.

PMID- 7521158
TI  - Sequence analysis of 16S rRNA from mycoplasmas by direct solid-phase DNA
      sequencing.
AB  - Automated solid-phase DNA sequencing was used for determination of partial 16S
      ribosomal DNA sequences of mycoplasmas. The sequence information was used to
      establish phylogenetic relationships of 11 different mycoplasmas whose 16S rRNA
      sequences had not been determined earlier. A biotinylated fragment corresponding
      to positions 344 to 939 in the Escherichia coli sequence was generated by PCR.
      The PCR product was immobilized onto streptavidin-coated paramagnetic beads, and
      direct sequencing was performed in both directions. One previously unclassified
      avian mycoplasma was found to belong to the Mycoplasma lipophilum cluster of the
      hominis group. Microheterogeneities were discovered in the rRNA operons of
      Mycoplasma mycoides subsp. mycoides (SC type), confirming the existence of two
      different rRNA operons. The 16S rRNA sequence of M. mycoides subsp. capri was
      identical to that of M. mycoides subsp. mycoides (type SC), except that no
      microheterogeneities were revealed. Furthermore, automated solid-phase DNA
      sequencing was used to identify a mycoplasmal contamination of a cell culture as
      Mycoplasma hyorhinis, which proved to be very difficult by conventional methods.
      The results suggest that the direct solid-phase DNA sequencing procedure is a
      powerful tool for identification of mycoplasmas and is also useful in taxonomic
      studies.

PMID- 7521159
TI  - Behavior of bacteria and antibiotics under space conditions.
AB  - We have previously reported an increase of the "resistance" to antibiotics of
      bacteria during space missions. In the present experiment, we studied the growth
      of Escherichia coli cultured in vitro in space in the presence of
      dihydrostreptomycin: tritiated and nontritiated. This experiment was carried out
      during the STS 42 mission aboard the U.S. Space Shuttle Discovery (IML-1
      program). Cells were cultured in plastic bags and growth was stopped at six
      different time points by lowering the temperature to 5 degrees C. Several methods
      were used: viable cell counting by Colony Forming Units; total cell number by
      optical densitometry; electron microscopy; radioactivity measurements. The
      investigations show no difference between flight and ground experiments for the
      cultures without antibiotic. The growth rate with antibiotic was accelerated in
      flight, the growth yield was not changed, and there were no differences in the
      ultrastructures. The results suggest some changes in antibiotic binding in space.
      We did not observe any differences between the cultures developed in flight in
      the 1-g centrifuge and the cultures placed in the static rack in microgravity.

PMID- 7521160
TI  - A putative sirolimus (rapamycin) effector protein.
AB  - Sirolimus (rapamycin), a new immunosuppressive drug, inhibits proliferation of a
      wide spectrum of T and B cells. The immunosuppressive mechanism of sirolimus is
      still unclear. We recently isolated a membrane associated protein with an
      apparent molecular weight of 210 kDa, p210, from cultured Molt 4 cells and BJAB
      cells and from normal human T cells using an affinity matrix method. The p210
      binds to sirolimus:FKBP12 complex, but only at background levels to FKBP12 alone,
      to FK506:FKBP12 complex, or sirolimus-biotin alone. Among the sirolimus analogs
      tested, the binding ability of p210 to drug:FKBP12 complexes correlates with the
      immunosuppressive activity of the drugs, suggesting that p210 is the sirolimus
      effector protein.

PMID- 7521162
TI  - Gln5 selectively monodansylated substance P as a sensitive tool for interaction
      studies with membranes.
AB  - Substance P (SP) is a neuropeptide endowed with several important biological
      activities both in the central and peripheral nervous system. Taking advantage of
      the presence of glutamine residues in SP, the peptide was labelled with the
      fluorescent probe monodansylcadaverine using the transglutaminase (TGase)
      reaction in order to study interactions between SP and model or natural
      membranes. Although it was verified that both adjacent glutamines of the peptide
      can act as substrate for TGase in a consecutive reaction, conditions were
      optimized to selectively label Gln5. This fluorescent SP analogue was found to
      adopt environment-dependent conformations similar to those of the natural peptide
      and proved to be functionally active on guinea pig trachea. Fluorescence
      spectroscopy was used to demonstrate the potential use of dansylated SP in
      studies involving interactions with membranes.

PMID- 7521161
TI  - Expression of inducible nitric oxide in human lung epithelial cells.
AB  - Nitric oxide (NO) is increased in the exhaled air of subjects with several airway
      disorders. To determine if cytokines could stimulate epithelial cells accounting
      for the increased NO, the capacity of the proinflammatory cytokines (cytomix:
      tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma) to
      increase inducible nitric oxide synthase (iNOS) was investigated in A549 and
      primary cultures of human bronchial epithelial cells. Cytomix induced a time
      dependent increase in nitrite levels in culture supernatant fluids (p < 0.05).
      Increased numbers of cells stained for iNOS and increased iNOS mRNA was detected
      in the cytokine-stimulated cells compared to control (p < 0.05). Dexamethasone
      diminished the cytokine-induced increase in nitrite, iNOS by immunocytochemistry,
      and iNOS mRNA. These data demonstrate that cytokines, such as those released by
      mononuclear cells, can induce lung epithelial iNOS expression and NO release, and
      that this is attenuated by dexamethasone.

PMID- 7521163
TI  - Extracellular ATP potentiates nitric oxide synthase expression induced by
      lipopolysaccharide in RAW 264.7 murine macrophages.
AB  - Inducible nitric oxide synthase (iNOS) activity in the murine macrophage cell
      line RAW 264.7 was increased from two- to four-fold after co-exposure of the
      cells to low doses of bacterial lipopolysaccharide (LPS) and micromolar ATP,
      compared to LPS alone. Extracellular ATP and its analogs "per se", i.e. without
      LPS, were not able to induce iNOS activity. The stimulating effect of UTP too,
      the concentration range of activity (1-100 mM nucleotides) and the rank of
      potency (ATP-gamma-S = AMP-PNP > ATP = ADP >> AMP-CPP = UTP) seem to indicate an
      involvement of P2y-type purinergic receptors. GTP, CTP and adenosine were
      virtually ineffective. These data suggest that binding of extracellular
      nucleotides to purinergic receptors may increase nitric oxide production by
      macrophages. This effect might occur in pathological conditions (i.e.
      inflammation/infection or trauma) where significant amounts of intracellular ATP
      can be released due to cellular damage.

PMID- 7521164
TI  - Genistein enhances the ICAM-mediated adhesion by inducing the expression of ICAM
      1 and its counter-receptors.
AB  - Binding of circulating cells to endothelium is mediated by recognition between
      endothelial adhesion molecules and their counter-receptors. The beta 2 integrins
      are a group of adhesion molecules, mainly expressed on leukocytes, that mediate
      intercellular binding by recognizing their counterparts on endothelial cells,
      among others ICAM-1. In this study we have studied the regulation of this
      interaction in myelomonocytic cells treated with genistein, a tyrosine kinase
      inhibitor with several other biological functions. We show that genistein
      upregulates the surface expression of the beta 2-integrins in the monoblastic THP
      1 and to a lesser extent in the promyelocytic HL-60 leukemia cell lines. This
      upregulation leads to an increase in the adherence of THP-1 cells to ICAM-1.
      Genistein also modulates the expression of ICAM-1 on endothelial cells by
      potentiating the upregulating effect of TNF and IFN-gamma. Genistein may thus
      enhance intercellular binding by affecting both the endothelium and the
      circulating cells.

PMID- 7521165
TI  - Neurotensin receptor and its mRNA are expressed in many human colon cancer cell
      lines but not in normal colonic epithelium: binding studies and RT-PCR
      experiments.
AB  - Neurotensin receptor expression was studied in 19 human colon cancer cell lines
      and normal human colon by i) binding experiments using [125I-Tyr3]-neurotensin;
      ii) RT-PCR analysis. The following data were obtained: 1) A single class of
      receptor (Kd ranging from 0.23 to 1.21 nM) was found in 9 out of 19 cell lines
      but not in normal colonic epithelium; 2) The Bmax was in the range between 1000
      and 85 fmoles/mg protein with SW48 > WiDR > Cl 19A > HCT116 > SW480 > SW620 > Cl
      16E > Cl 27H > HT-29. No specific binding was measurable in Caco-2, FRI, CBS, EB,
      HCT-8, 320HRS, 320DM and LS174T cell lines; 3) A single RT-PCR product was
      observed in HT-29, SW48, WIDR, Cl 19A, SW480, Cl 16E, Cl 27H, SW620 and HCT116,
      but not in other cell lines or in normal human colon. It is concluded that the
      expression of neurotensin receptors in human colon cancer cells is regulated at
      the mRNA level and occurs upon malignancy in > 40% of colon cancer cell lines.

PMID- 7521166
TI  - Calcium-dependent inhibition of constitutive nitric oxide synthase.
AB  - The objective of these investigations was to study the regulatory properties of
      brain constitutive NO synthase. NOS activity was determined in 18,000 X g
      supernatant by conversion of 3H-L-arginine to 3H-L-citrulline in the presence of
      NADPH. The expression of catalytic activity of NOS required the presence of
      calcium ion and calmodulin. The preincubation of enzyme preparations at 37
      degrees C in standard reaction mixture led to time-dependent inhibition of L
      citrulline formation. This inhibition also required the presence of calcium ion
      during preincubation phase, and the enzyme remained calmodulin-dependent as
      exhibited by sensitivity to calmodulin antagonists trifluoperazine (TFP) and
      calcineurin. The modified enzyme showed significant decrease in the Vmax with
      NADPH and L-arginine without any change in apparent Km. Inclusion of protease
      inhibitors, leupeptin, pepstatin A, PMSF and soyabean trypsin inhibitor to the
      preparations did not alter preincubation-dependent inhibition of NO synthase.
      Thus, the calcium-dependent inhibitory phenomenon was not due to either the
      denaturation or proteolysis or the loss of calmodulin sensitivity of NO synthase.
      These observations indicate that cytosolic isoform of constitutive NO synthase
      undergoes dual regulation by physiological concentrations of calcium ion.

PMID- 7521168
TI  - Monoamine metabolites in normal human cerebrospinal fluid and in degenerative
      diseases of the central nervous system.
AB  - Measurement of monoamine metabolites in cerebrospinal fluid (CSF) has been one of
      the few methods available to study monoamine transmitter function in the human
      central nervous system (CNS). It has steadily proved to be of much use in
      clinical research of neurological and psychiatric diseases, in which altered
      functions of central monoamine neurotransmitters have been identified. In this
      work 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 3,4-dihydroxyphenylacetic acid
      (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were
      quantified in normal CSF and in patients with untreated Parkinson's disease (PD)
      and olivopontocerebellar atrophy (OPCA). Normal CSF was obtained from 162
      patients at the time of spinal anesthesia for surgery. Reference values for
      monoamine metabolites were established for normal adult lumbar CSF. Up to the age
      of 70 years no relation of monoamine metabolite concentration with age or sex
      were encountered. In individuals above 70 years of age higher levels of MHPG,
      HVA, and 5-HIAA were present in women, while in men only higher levels of MHPG
      could be detected. A strong correlation between 5-HIAA and HVA concentrations
      were observed in all groups. PD patients exhibited normal CSF metabolite levels,
      but an altered 5-HIAA/HVA ratio, favoring 5-HIAA. Dominant and recessive OPCA
      differed essentially in HVA concentration-diminished in the first group and
      elevated in the last. Comparing the results obtained in PD and dominant OPCA, we
      suggest that the decrease of CSF HVA in the latter group might not reflect
      nigrostriatal degeneration as we previously thought. Possibly another factor
      influencing dopamine function in the CNS is involved.

PMID- 7521169
TI  - The management of renal cell carcinoma.

PMID- 7521167
TI  - HIV coating gp 120 glycoprotein-dependent prostaglandin E2 release by human
      cultured astrocytoma cells is regulated by nitric oxide formation.
AB  - The role of the L-arginine-NO pathway on the formation of PGE2 by cultured
      astroglial cells incubated with the HIV coating glycoprotein gp120 was
      investigated. Preincubation of human cultured T 67 astrocytoma cells with gp 120
      (100-500 nM) produced a significant increase of nitrite (the breakdown product of
      NO) and PGE2 in cell supernatants. The effect of gp 120 on both nitrite and PGE2
      production was antagonized by inhibition of NO synthase by L-NAME (20-300
      microM). The inhibition of gp120-induced PGE2 production by L-NAME was reverted
      by addition of arachidonic acid (30 microM), an effect antagonized by the cyclo
      oxygenase inhibitor indomethacin (10 microM). Methylen bleu, an inhibitor of the
      biological activity of NO acting at the guanylate cyclase level failed to affect
      gp 120-mediated PGE2 release showing that the increase of cGMP subsequent to NO
      production was not involved in the modulatory activity of NO on arachidonic acid
      cascade. On the basis of present experiments we conclude that gp-120-induced
      release of PGE2 by astroglial cells is driven by NO, thereby contributing in the
      involvement of glial cells in HIV-related cerebral disorders.

PMID- 7521170
TI  - Binding and intracellular fate of beta-very low density lipoprotein in isolated
      rat liver parenchymal cells.
AB  - Binding of rabbit 125I-tyramine-cellobiose-beta-very low density lipoprotein
      (125ITC-beta-VLDL) was saturable both in suspended and cultured rat liver
      parenchymal cells, and in isolated rat liver membrane fractions. The specific
      binding had KD values ranging from 8 to 10 micrograms/ml. At 37 degrees C beta
      VLDL was internalized and degraded in parenchymal cells in culture, but only
      negligible degradation was measured in suspended cells. In cultured cells the
      degradation was inhibited by lysosomal and microtubular inhibitors, these agents
      had no effects in suspended cells. Studies of release suggested internalization
      in suspended cells and subcellular fractionation experiments confirmed that
      internalized 125ITC-beta-VLDL reached the lysosomal compartment in cultured
      cells, but not in suspended cells. Since lactosylated (lac-) beta-VLDL was taken
      up and degraded efficiently by suspended cells, these cells are not in general
      unable to transport large lipoprotein particles to the lysosomes. We believe that
      beta-VLDL does not dissociate from the receptor in the endosomes and therefore is
      retroendocytosed to the plasma membrane. In isolated parenchymal cells the beta
      VLDL binding site is supposedly different from the methylamine-activated-alpha 2
      macroglobulin (ma-alpha 2M) binding site, since; 1) Excess beta-VLDL did not
      reduce ma-alpha 2M binding; 2) In suspended parenchymal cells ma-alpha 2M was
      readily degraded, whereas beta-VLDL was not degraded and 3) The binding of beta
      VLDL was not Ca+(+)-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521171
TI  - Interactions of alpha-1-antichymotrypsin, alpha-1-proteinase inhibitor, and alpha
      2-macroglobulin with the fungal enzyme, seaprose.
AB  - The Semi-alkaline proteinase (Seaprose) from Aspergillus melleus has been tested
      for its ability to either inactivate or form complexes with three human plasma
      proteinase inhibitors, alpha-2-macroglobulin, alpha-1-antichymotrypsin and alpha
      1-proteinase inhibitor. alpha-2-Macroglobulin was found to inhibit Seaprose, with
      two mol of enzyme being complexed per mol of inhibitor. However, alpha-1
      proteinase inhibitor was rapidly inactivated by the fungal enzyme as a result of
      cleavage of the inhibitor, primarily at the P1-P'1 reactive site. Curiously,
      alpha-1-antichymotrypsin was found to form complexes with Seaprose and also be
      inactivated by this inhibitor. Apparently, the enzyme can recognize two sites
      within the reactive site loop of the inhibitor, one at the P4-P'5 position,
      resulting in inactivation, and one presumably at the P1-P'1 reactive site which
      results in complex formation. The fact that Seaprose can so rapidly inactivate
      alpha-1-proteinase inhibitor, the primary regulator of neutrophil elastase,
      indicates that Seaprose would be a rather poor choice for therapy in individuals
      with bronchial mucus hypersecretion.

PMID- 7521172
TI  - Selectins--glycoprotein targets for therapeutic intervention in inflammation.
AB  - Inflammation can be a beneficial response in the host for the control of
      infection and injury. However, occasionally, the inflammatory response can result
      in acute systemic collapse or, more frequently, a chronic reaction such as that
      observed in autoimmune disease, Crohn's disease and asthma. Injury to tissues or
      organs results in leukocyte adhesion to the endothelial cell surface, followed by
      diapedesis. Investigation of the initial leukocyte-endothelium adhesion processes
      has clearly shown the involvement of an inducible set of molecules, called
      selectins, on the endothelial and leukocyte cell surfaces. These molecules are of
      interest as the interactions with their respective ligands appear to involve
      carbohydrates. The exact nature of these interactions is still being elucidated.
      Therapeutic intervention using carbohydrate small-molecule mimetics may be
      beneficial in the modification of the inflammatory process.

PMID- 7521173
TI  - Prostate-specific antigen and human glandular kallikrein: two kallikreins of the
      human prostate.
AB  - Prostate-specific antigen (PSA) is a 33 kD protein synthesized in the epithelial
      cells of the prostate gland. It is a serine protease that belongs to the subgroup
      of kallikreins, among which it is very similar to a putative enzyme called human
      glandular kallikrein (hGK-1). Although the hGK-1 enzyme remains to be
      characterized in vivo, the hGK-1 gene is expressed in the same prostatic
      epithelial cells as the PSA gene. Expression of the PSA gene is under complex
      control and the steady-state level of PSA mRNA is increased by androgens, and
      decreased by epidermal growth factor and activation of protein kinase C. This
      suggests the existence of several regulatory elements within the cis-acting
      control elements of the PSA gene. As a seminal serine protease, PSA has been
      shown to digest the high molecular weight seminal vesicle protein, seminogelin.
      However, it is likely that this does not constitute the only natural substrate of
      PSA, as PSA has been shown to degrade insulin-like growth factor-binding protein
      3. Serum PSA concentrations are frequently increased in patients with prostatic
      cancer, but this is also the case in patients with benign prostatic hyperplasia.
      Thus, PSA measurements alone are not useful as a screening tool for undiagnosed
      prostatic cancer. However, serum PSA concentrations can be successfully used
      together with other methods in diagnosing prostatic diseases and in monitoring
      the successfulness of treatments for prostatic cancer.

PMID- 7521174
TI  - Epidermolysis bullosa: pathogenetic pathways from mutations to symptoms.
AB  - Recent developments of the molecular and cell biology of the cutaneous basement
      membrane zone have greatly advanced our understanding of the pathomechanisms
      underlying skin blistering disorders. The heritable blistering diseases, the
      epidermolysis bullosa group, have been investigated as model diseases. Defects in
      genes coding for the structural proteins of the basement membrane zone have been
      defined in some EB subtypes and abnormal expression of the structural proteins in
      others. In vitro studies utilizing cutaneous cells derived from epidermolysis
      bullosa skin have helped to understand the pathogenetic pathways that lead from
      the mutation to the symptom, skin blistering. The data accumulated from analyses
      of the genetic disorders will yield indirect information on the normal physiology
      of the skin and be highly relevant for discerning the etiopathogenesis of
      acquired blistering diseases and for dermal-epidermal interactions required for
      reparative processes, such as wound healing.

PMID- 7521175
TI  - La "formazione continua" del medico europeo [The "continuing education" of the
      European physician.

PMID- 7521176
TI  - [Quality control in the input of data relative to the infective disease
      notification system].

PMID- 7521178
TI  - [Tobacco smoking among high-school students of Local Health Units No. 9 and 19 in
      the Le Marche region].

PMID- 7521179
TI  - [The prevalence of surgical wound infections in the Ligurian Regional Hospital].

PMID- 7521177
TI  - [The audit and QA in good clinical practice (GCP)].

PMID- 7521180
TI  - [An increase in tetanus in Italy in 1991-1993].

PMID- 7521181
TI  - [Precooked vegetables as the possible vehicles of motile Yersinia enterocolitica
      and Aeromonas ].

PMID- 7521183
TI  - Detection of mRNA expression in a single cell by direct RT-PCR.

PMID- 7521182
TI  - [Shore discharges and lake waters].

PMID- 7521184
TI  - Effects of ethanol and paraformaldehyde on RNA yield and quality.

PMID- 7521185
TI  - Nuclear runoff transcription analysis using chemiluminescent detection.

PMID- 7521187
TI  - Highly sensitive northern hybridization of rare mRNA using a positively charged
      nylon membrane.
AB  - The effect of different RNA fixation methods using Hybond-N and Hybond-N+ nylon
      membranes in Northern blot experiments was analyzed with human glyceraldehyde-3
      phosphate dehydrogenase and human interleukin-3 receptor alpha-subunit as
      radioactive labeled DNA probes. Highest sensitivity could be achieved by mild
      alkaline fixation of RNA to positively charged Hybond-N+ nylon membrane. Fixation
      by UV light resulted in reduced sensitivity in comparison with alkaline
      treatment. Fixation of RNA to Hybond-N or -N+ membranes by baking for 2 h at 80
      degrees C resulted in a strong decrease in sensitivity and should be avoided when
      using modified nylon membranes in Northern hybridizations.

PMID- 7521186
TI  - Detection of triplex-forming RNA oligonucleotides by triplex blotting.
AB  - Triplex formation with RNA oligonucleotides and double-stranded (ds) DNA may
      provide a means of controlling gene expression from specific promoters and/or
      creating more selective DNA cleaving agents. We report the development of a novel
      technique, called triplex blotting, designed to detect RNA species capable of
      triplex formation with radiolabeled dsDNA probes within a background of total
      cellular RNA. Triplex blotting offers a new approach for screening potential RNA
      sequences for triplex formation with dsDNA targets, for comparing relative
      binding affinities of various triplex-forming RNAs and for confirming the
      specificity of triplex formation of a DNA target probe within total cellular RNA.
      In addition, the technique allows for repeated probing of the same filter while
      varying critical hybridization conditions such as pH, temperature or ionic
      strength.

PMID- 7521189
TI  - Technical report. Video imaging of ethidium bromide-stained DNA gels with surface
      UV illumination.
AB  - We describe here the use of surface UV illumination to record ethidium bromide
      stained DNA gels with a video camera. This mode of illumination allows the use of
      a standard video camera equipped with a red filter and results in a high signal
      strength. The assembly of a low-cost video system on this basis is described. It
      uses the public domain software called Image on a Macintosh computer and
      PostScript laser printer or a thermal printer to generate hard copies. The setup
      is sensitive enough to detect 500 pg of DNA on an ethidium bromide-stained DNA
      gel. The UV illumination method described here can also greatly improve the
      sensitivity of existing video recording equipment.

PMID- 7521188
TI  - A method for the elimination of false positives generated by the mRNA
      differential display technique.
AB  - The recently described mRNA differential display method provides an attractive
      tool for the isolation of genes showing regulated expression in a variety of
      systems. A key step in this technique consists of the isolation of PCR
      synthesized radioactive cDNAs corresponding to differentially expressed mRNAs.
      Here, we show that the purified cDNAs remain contaminated with unrelated cDNA
      sequences that may lead to the artifactual isolation of false positives in the
      subsequent steps of the method. A powerful assay for the detection and
      elimination of this contaminating material, allowing the specific isolation of
      clones corresponding to the regulated genes identified by the differential
      display, is provided.

PMID- 7521190
TI  - Smoking in pregnancy and child development to age 9 years.
AB  - This study examined the association between women's retrospective reports of
      smoking during pregnancy and subsequent language, cognitive, behavioural and
      physical development in their children up to age 9 years. While there was a
      strong association between maternal smoking and an index of disadvantageous child
      rearing, maternal smoking was not associated with more general family
      disadvantage. After controlling for levels of background disadvantage, no
      relationship was found between reports of smoking and language, cognitive or
      physical development. However, smoking was related to maternal reports of
      behaviour problems at age of school entry. Possible explanations for this
      relationship are discussed.

PMID- 7521192
TI  - HIV-1 reverse transcriptase codon 215 mutation and clinical outcome in children
      treated with zidovudine.
AB  - OBJECTIVE: In HIV-infected adults prolonged monotherapy with zidovudine may be
      associated with the appearance of HIV strains with decreased zidovudine
      sensitivity, owing to specific mutations in the reverse transcriptase (RT) gene,
      and this has been suggested to be a reason for reduced zidovudine efficacy. This
      study was undertaken to determine the appearance of mutation at codon 215 of the
      RT gene in proviral DNA from PBMCs in HIV-infected children. DESIGN: A
      prospective, open study. SETTING: A University Pediatric Department. PATIENTS AND
      METHODS: Nineteen HIV-infected symptomatic children were treated with zidovudine
      for a median of 24 months. Clinical and laboratory controls for HIV infection
      status were performed monthly. Mutant proviral sequences were evaluated at the
      start of therapy, every 3 months during the first 6 months of therapy, and every
      6 months thereafter. Clinical outcome was defined as stable or deteriorating.
      RESULTS: No child had proviral sequences mutant at codon 215 before starting
      zidovudine. Ten of 13 children who had received zidovudine for more than 6 months
      developed mutant proviral sequences. All the children (10 of 10) with mutant
      proviral sequences had a deteriorating clinical condition, compared to none of
      those (0 of 9) without mutation at codon 215. CONCLUSION: The appearance of HIV-1
      codon 215 mutation seems to be strongly associated with zidovudine therapy and
      with clinical progression of HIV disease in children.

PMID- 7521191
TI  - Linear epitopes of HIV-1, presented as hybrids with Escherichia coli beta
      galactosidase or synthetic peptides.
AB  - HIV-1 B cell epitopes from gp41, the T cell epitope of p34pol, and a cluster of B
      and T epitopes from p17gag were selected. The epitopes were presented as
      synthetic peptides and as either N- or C-terminal insertions into beta
      galactosidase. Hybrids were efficiently expressed in E. coli and easily purified
      when epitopes were inserted at the beta-galactosidase C terminus. Sera from HIV-1
      infected individuals reacted in peptide- and hybrid protein-based enzyme-linked
      immunosorbent assays (ELISAs) mostly with the immunodominant site of gp41. The
      second site of gp41 and also sites from p17 and p34 appeared to be
      immunorecessive. A few of the HIV-1-positive sera exhibited several
      immunorecessive reactivities. HIV-1-positive sera from the former Soviet Union
      and Cuba had reactivities similar to those of American, African, and west
      European sera. Some sera could not be evaluated as specifically HIV-1
      seropositive because of their broad reactivities with a multitude of peptides and
      proteins, unrelated to HIV-1. Extensive tests were performed to define unspecific
      reactivities by absorption, blocking, and sandwich ELISAs. The application of the
      hybrid protein assay substantially improved the specificity of the ELISA tests.
      Thus, hybrid protein-based ELISAs appeared to be more suitable than peptide-based
      ELISAs, especially for the evaluation of immunorecessive reactivities.

PMID- 7521193
TI  - Organic thiophosphate WR-151327 suppresses expression of HIV in chronically
      infected cells.
AB  - Reducing agents such as glutathione (GSH), glutathione ester (GSE), and N
      acetylcysteine (NAC) have been shown to suppress the induction of HIV expression
      in chronically infected cells stimulated by cytokines. We present data which show
      the effects of the organic thiophosphate WR-151327 on the expression of latent
      HIV in U1 cells. The chronically infected promonocytic cell line U1
      constitutively expresses low levels of HIV that can be increased by 13-phorbol 12
      myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), and
      granulocyte/monocyte colony-stimulating factor (GM-CSF). WR-151327 suppressed, in
      dose-dependent fashion, the reverse transcriptase (RT) activity induced by TNF
      alpha, GM-CSF, and PMA. The maximal decrease in RT activity was 70, 80, and 50%,
      respectively. Pretreatment with WR-151327 also suppressed the induction of total
      HIV protein synthesis, as shown by Western blot analysis. In addition, WR-151327
      suppressed HIV-LTR-CAT activity in transfected human rhabdomyosarcoma cells (RD).
      Suppression of HIV expression by WR-151327 was observed in the absence of a
      cytotoxic or cytostatic effect. Incubation of WR-151327 with human recombinant
      TNF-alpha for 6 hr at 37 degrees C did not alter the capacity of TNF-alpha to
      induce the expression of HIV. Our observations further support the hypothesis
      that reducing agents are important in the control of HIV replication and that the
      clinical evaluation of WR-151327 may be indicated.

PMID- 7521194
TI  - 131I-metaiodobenzylguanidine therapy for malignant pheochromocytoma.
AB  - 131I-metaiodobenzylguanidine (MIBG) therapy was given to five patients with
      malignant pheochromocytoma. The patients received 1-3 doses of 3.33-4.625 GBq
      (total dose: 3.7 to 10.73 GBq). Partial tumor regression was observed in two
      patients, the tumor was unchanged in two patients, and slow progression was noted
      in one patient. Marked improvement in clinical symptoms was achieved in four
      patients. The other patient had no symptoms before 131I-MIBG treatment, but the
      serum epinephrine and dopamine decreased. There were no severe untoward responses
      in four patients. However, one patient developed transient but severe orthostatic
      hypotension, hypertension, and hyperglycemia from 1 week to 1 month after 131I
      MIBG administration. Although complete remission was not obtained, all the
      patients achieved some benefit from 131I-MIBG therapy. Thus, 131I-MIBG appears to
      be useful for the palliation of malignant pheochromocytoma.

PMID- 7521195
TI  - Analysis of factors affecting uptake of Tc-99m Sn-N-pyridoxyl-5-methyltryptophan
      by hepatocellular carcinoma.
AB  - We performed Tc-99m PMT imaging in 176 patients with HCC and evaluated factors
      affecting 99mTc-PMT uptake by HCC with a logistic model. The probability of HCC
      showing increase in uptake of the radioisotope was 104.6 times higher in patients
      with the Ed I type than in those with the Ed III type and 12.1 times higher in
      patients with a tumor diameter of 5.0-7.9 cm than in those with a tumor diameter
      of 2.0-5.0 cm. Among the other variables, the serum AFP level and sex were
      suggested to have effects similar to those of the tumor size on Tc-99m PMT uptake
      by HCC. The grade of morphological differentiation of the tumor was therefore
      most markedly related to Tc-99m PMT uptake.

PMID- 7521197
TI  - Clinical applications of IL-2.
AB  - Several years of clinical trials with IL-2, including modifications of dose and
      schedule and combinations with other biologic agents or chemotherapy, have shown
      much more limited anticancer activity for this agent than was anticipated from
      the preclinical studies. Even for its FDA-approved indication (metastatic renal
      cell carcinoma patients with good performance status), IL-2 probably benefits
      only a small subset of patients, and no prognostic factors have yet been
      identified to pinpoint these patients. In addition, clinical activity in patients
      with renal cell carcinoma treated with high-dose IL-2 is achieved at the expense
      of substantial acute toxicity. Nonetheless, the durable complete responses
      observed in a small percentage of patients with metastatic renal cell carcinoma
      and metastatic melanoma, and the potent immunomodulatory effects of IL-2, suggest
      that it may yet become an important anticancer agent, perhaps in association with
      active and adoptive immunotherapy. The agent also has shown potential for the
      treatment of infectious diseases and immunodeficiency states.

PMID- 7521196
TI  - Usefulness of molecular genetic markers in the typing of Salmonella enterica
      serovar Enteritidis causing a food-borne outbreak.
AB  - A combination of serotyping-phagetyping and three molecular genetic markers
      (plasmid analysis, chromosomic DNA restriction pattern and ribosomal RNA gene
      restriction pattern or ribotyping) was used in the typing of Salmonella enterica
      causing a food-borne outbreak. The isolates analysed, 29 from stools and eight
      from foods, belonging to serovar Enteritidis-phagetype A, carried a 36-MDa
      plasmid, showed a similar DNA restriction pattern and the same ribopattern. These
      data indicate that only one strain was involved. The DNA pattern and ribopattern
      of this strain were indistinguishable from the patterns of a serovar Enteritidis
      phagetype A strain which has caused salmonellosis in Asturias, Spain, since, at
      least, 1984.

PMID- 7521198
TI  - Involvement of non-receptor protein tyrosine kinases in expression of
      differentiated phenotype by cells of retinal origin.
AB  - Regulation of phenotypic expression in epithelia in general, and of two epithelia
      of the retina, the neural retina and retinal pigment epithelium in particular, is
      dependent on interactions with extracellular environment. Extracellular
      environment may comprise acellular substrata as well as other cells. Non-receptor
      protein tyrosine kinases are involved in transmembrane transmission of signals
      from extracellular milieu, via the cytoskeleton to the nucleus. We describe
      distribution of these kinases in cells of retinal origin and show that two of
      them, pp125FAK and pp60c-src redistribute intracellularly in a differentiation
      dependent manner. Next we discuss roles that adhesion-related non-receptor
      protein tyrosine kinases might play in phenotypic expression by the retinal
      epithelia.

PMID- 7521199
TI  - Developing blood vessels and associated extracellular matrix as substrates for
      neural crest migration in Japanese quail, Coturnix coturnix japonica.
AB  - Japanese quail embryos were used to examine paths of neural crest cell (NC)
      migration in relationship to the embryonic vasculature. Immunolabeling for NC,
      angioblasts and the extracellular matrix (ECM) glycoproteins fibronectin (FN),
      laminin (LN) and tenascin (TN) revealed several instances where spatiotemporal
      patterns of NC migration coincide with the embryonic vascular pattern and its
      associated ECM. An in vitro model for angiogenesis was modified to include NC,
      and associations with "capillary-like" endothelial cell structures were
      demonstrated. A working hypothesis is that the embryonic vasculature may, in
      specific instances, be used as a substratum for directed NC migration and that
      these interactions are mediated primarily through the adhesive interactions of
      FN. Some members of the TN family of glycoproteins, through their relatively non
      adhesive properties, may act to help guide neural crest cells to the FN-rich
      blood vessel surface.

PMID- 7521200
TI  - The histopathology of Langerhans cell histiocytosis.
AB  - Selected aspects of the histopathology of Langerhans cell histiocytosis
      representing diagnostic difficulty and/or controversy are presented with emphasis
      on the composition of pathological lesions. Lesional cell phenotypes and the
      factors influencing variations are noted. Features of several skin-based
      histiocytic disorders, dermatopathic lymphadenopathy and Rosai-Dorfman disease
      are compared. Associations between Langerhans cell histiocytosis and juvenile
      xanthogranuloma and malignant disorders are considered. Observations of potential
      significance in the eventual elucidation of the pathogenesis of these enigmatic
      diseases are presented.

PMID- 7521201
TI  - Detection of clonal histiocytes in Langerhans cell histiocytosis: biology and
      clinical significance.
AB  - Although the first clinical description of Langerhans cell histiocytosis (LCH)
      was published over a century ago, the aetiology and pathogenesis of this
      enigmatic disorder are still remained unknown. Viral, immunological, neoplastic
      and other pathogenetic mechanisms have been considered, but none has been proven.
      The prevailing opinion is that LCH is a reactive disorder rather than a
      neoplastic process, but this presumption has never been definitively tested. A
      key feature of a neoplasm is its clonal derivation from a single cell. To
      determine if LCH is a polyclonal reactive or a clonal disorder, we and others
      have recently used molecular biological techniques to assess clonality in LCH.
      Using X chromosome-linked DNA probes that can detect clonal or polyclonal X
      chromosome inactivation patterns in female tissues, clonal CD1a+ histiocytes have
      now been detected in the lesional tissues in each of 16 females affected with
      LCH. Most of these patients were studied prior to the initiation of therapy.
      Lymphoid clonality was excluded in all cases in which it was studied, confirming
      that the clonal cells in LCH are the CD1a+ dendritic cells presumed to be pivotal
      in this disorder. Two distinct lesions (a pre-treatment bone biopsy and a lymph
      node biopsied 3 years later) have been studied in only one case to date; the same
      clonal pattern of X chromosome inactivation was observed, consistent with
      persistence of the same clone during this patient's disease course.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7521203
TI  - Clinical prognostic significance of tumour angiogenesis.
AB  - BACKGROUND: The importance of tumour angiogenesis in the process of tumour growth
      and metastasis has recently gained wide acceptance. This has lead to intense
      investigation into the biology of tumour angiogenesis and its clinical
      significance. An understanding of angiogenesis may allow therapeutic modulation
      in order to interrupt the progression from tumourigenesis to metastatic disease
      and control growth of distant metastases. DESIGN: A review was undertaken of
      studies relating clinical outcome to the assessment of tumour angiogenesis in
      patients with cancer. RESULTS: Studies have been recently reported in a variety
      of tumours, particularly early breast cancer and melanoma. Quantitative
      pathology, using microvessel counting, has been the main method applied. However
      assessment of angiogenic growth factors may provide an alternative. In early
      breast cancer many studies have shown a worse prognosis for those patients with
      highly vascular tumours. The prognostic influence of tumour angiogenesis is
      independent of conventional prognostic indicators. Similar, although more varied
      results, have been obtained in studies of melanoma and other tumour types.
      CONCLUSION: Tumour angiogenesis, as assessed with quantitative pathology, is an
      important prognostic indicator in early breast cancer and possibly in other
      tumour types. Further confirmatory studies are required before this indicator is
      routinely used to guide treatment selection. Assessment of tumour angiogenesis
      will be increasingly important in the investigation of new therapies aimed at
      inhibiting angiogenesis or targeting tumour vasculature.

PMID- 7521202
TI  - The normal Langerhans cell and the LCH cell.
AB  - The epidermal Langerhans cell is the bone marrow-derived dendritic, antigen
      presenting cell of the skin. It is characterised by a unique intracytoplasmic
      organelle--the Birbeck granule--and constitutively expresses class II MHC
      molecules and the CD1a glycoprotein. The Langerhans cell represents one of the
      most potent antigen-presenting cells of the body, and fulfils an important role
      in detecting foreign antigen entering the body through the skin and in immune
      surveillance. The distribution of Langerhans cells is restricted to the skin,
      lymph nodes, bronchial mucosa and thymus. The discovery by Nezelof in 1973 that
      the lesional cells in the disease then called 'Histiocytosis X' contained Birbeck
      granules established the close relationship between the Langerhans cell and this
      disease and led ultimately to the adoption of the name Langerhans cell
      histiocytosis to replace the older term. The LCH cell expresses the phenotype of
      a Langerhans cell apparently 'fixed' at an early stage of cell activation. The
      LCH cell is, however, functionally defective in antigen presentation, and the
      tissue distribution of the disease--affecting bone, skin, lymph node, lung,
      liver, spleen, CNS, gastro-intestinal tract and bone marrow--is quite different
      from the normal distribution of the Langerhans cell. Studies are now under way
      throughout the world to investigate the relationship between the normal
      Langerhans cell and the LCH cell. Specifically we need to identify whether the
      LCH cell is a cell arrested at a specific time in normal Langerhans cell ontogeny
      or if it represents a response to a biological insult to the mature Langerhans
      cell or its precursors.

PMID- 7521206
TI  - A phase I trial of continuous infusion interleukin-4 (IL-4) alone and following
      interleukin-2 (IL-2) in cancer patients.
AB  - BACKGROUND: Interleukin-4 (IL-4) can enhance immune function within various
      leukocyte populations and mediate antitumor effects in mice. In vitro, IL-4
      activation of human lymphocytes is enhanced by prior exposure to interleukin-2
      (IL-2). This phase I trial of continuous intravenous infusion (CI i.v.) IL-4 was
      performed to determine its toxicity and biologic activity. IL-2 was administered
      prior to a second course of IL-4 in the same patients to determine whether IL-2
      exposure can enhance IL-4 effects in vivo. PATIENTS AND METHODS: Seventeen
      patients with non-hematologic malignancies were entered on this trial. Treatment
      consisted of 7 days of CI i.v. IL-4 followed by a 2 week period off therapy, then
      a 4 day course of CI i.v. IL-2 at 11.2 MIU/m2/day followed by 3 days rest, and
      then a second 7 day course of CI i.v. IL-4. IL-4 dose escalation included 40
      micrograms/m2/day (6 pts.), 120 micrograms/m2/day (3 pts.), 360 micrograms/m2/day
      (5 pts.), and 600 micrograms/m2/day (3 pts.). RESULTS: Dose limiting toxicity
      occurred at 600 micrograms/m2/day of IL-4; a dose at which 2 of 3 patients
      exhibited a vascular leak syndrome characterized by weight gain, peripheral
      edema, effusions, oliguria, and diffuse rash. Pretreatment with IL-2 did not
      significantly enhance IL-4 toxicity in the 40-360 micrograms dose range. IL-4
      treatment was associated with a modest, but significant increase in peripheral
      eosinophil counts (p = 0.004), but no consistent change in lymphocyte phenotype
      or function. Patients treated at the higher dose of IL-4 (360 micrograms)
      administered following IL-2, exhibited a marked increase in peripheral
      eosinophils after IL-4 therapy (p = 0.007). Following the second course of IL-4,
      we observed increases in the percent CD56+ (NK/LAK marker) lymphocytes (mean
      increase = 6.8%), above levels induced by the preceding IL-2 treatment (p =
      0.055). A single minor durable tumor response was seen in a patient with
      metastatic renal cancer. CONCLUSIONS: IL-4 administered at 360 micrograms/m2/day
      CI i.v. over seven days is the maximum tolerated dose and is tolerable following
      a 4 day course of IL-2. IL-4 therapy alone is associated with a modest
      eosinophilia. In patients receiving IL-2 prior to IL-4, both circulating
      eosinophils and CD56+ cells increased above levels observed early after IL-2
      treatment. Based upon these results, phase II trials of IL-4 in combination with
      IL-2 could be planned in 'IL-2 sensitive' malignancies.

PMID- 7521205
TI  - Heterogeneity of acute lymphoblastic leukemia in HIV-seropositive patients.
AB  - BACKGROUND: As opposed to large-cell or Burkitt's-type non-Hodgkin's lymphoma,
      acute lymphoblastic leukemia (ALL) is rarely observed in HIV-seropositive
      patients and is not a criteria of AIDS in the 1986 classification established by
      the C.D.C. Furthermore, the few cases of ALL reported so far were B-cell ALL,
      Burkitt's-type. DESIGN: We recently observed, with unexpected frequency, ALL
      cases in this setting: over a 5-year period, 5 of 25 HIV-positive patients
      referred to our center for hematological malignancies, had ALL. Three patients,
      who had previously been asymptomatic with regard to HIV infection, had typical
      Burkitt's-type ALL. Complete remission was achieved in all cases with high-dose
      lymphoma-type chemotherapy regimens, but 2 patients relapsed 3 and 27 months
      after diagnosis. Their clinical characteristics and outcome are discussed with
      reference to the cases reported thus far in the literature. One patient had
      common early pre-B ALL with the Philadelphia chromosome, and one had a T-cell ALL
      with an unusual CD7+, CD4-, CD8- phenotype. Prognosis was very poor in both
      cases. CONCLUSION: The exact incidence and the therapeutic management of B-cell
      ALL in HIV-positive patients warrants further evaluation. In addition, we show
      that there may be a heterogeneity among ALL cases in this setting, with the first
      description of 2 non-Burkitt's ALL with atypical features in HIV-positive
      patients.

PMID- 7521207
TI  - The management of non-seminomatous germ cell tumours (GCT).

PMID- 7521204
TI  - Results of CAV regimen (CCNU, melphalan, and VP-16) as third-line salvage therapy
      for Hodgkin's disease.
AB  - BACKGROUND: A prospective study was conducted to assess the efficacy and toxicity
      of a salvage regimen consisting of CCNU, Melphalan, and VP-16 (CAV) given at 28
      day intervals in patients with Hodgkin's disease (HD) relapsing after primary
      therapy or refractory to the alternating MOPP/ABVD regimen. PATIENTS AND METHODS:
      This study included 58 patients (median age: 34 years), with resistant or
      relapsing HD. Primary therapy had consisted of alternating MOPP/ABVD (81%) or
      MOPP alone (19%); 38% of patients were relapsing from prior complete remission
      (CR) while 62% had resistant disease. Extranodal disease was present in 55% and B
      symptoms in 72% of patients; one-fifth had bulky disease and/or bone marrow
      involvement. The CAV was used as first salvage in half of the patients. RESULTS:
      Complete remission was obtained in 17 patients (29%); unfavorable factors for CR
      in univariate analysis were the presence of bulky disease and the failure to
      achieve CR with prior therapy. Nine patients (53% of remitters) have subsequently
      relapsed with a 10-month median duration of CR. The 3-year overall survival after
      CAV was 25% with an 18-month median survival; significant differences in survival
      were found according to the extent of disease, the presence of B-symptoms and the
      HD status (prior sensitive or resistant disease, first or subsequent relapse).
      Seven patients are long-term remitters (12%), and one of them has been given high
      dose chemotherapy and autologous bone marrow transplantation at relapse after
      CAV. The CAV toxicity was mostly hematological; severe pancytopenia occurred in
      six cases with two cases of fatal infections and one of fatal hemorrhage.
      CONCLUSION: CAV therapy was moderately effective as third-line salvage in
      patients with HD resistant to alternating MOPP/ABVD or previously given two
      different regimens for relapse; the toxicity was mostly hematological and
      supportive therapy was needed in one-third of the patients.

PMID- 7521208
TI  - Severe asthenia and fatigue caused by recombinant human granulocyte colony
      stimulating factor (rh G-CSF)

PMID- 7521209
TI  - The conformation of the sialyl Lewis X ligand changes upon binding to E-selectin.
AB  - High-field NMR spectroscopy has been used to study the complex formed by the
      tetrasaccharide sialyl Lewis X and its receptor, E-selectin. Transferred NOEs
      demonstrate a specific interaction between the protein and ligand and enable
      measurement of the dissociation constant for the complex to be between
      approximately 1.1 and 2.0 mM. Differences between Overhauser spectra for free and
      bound sialyl Lewis X highlight a conformational change upon binding. This can be
      pinpointed to a change in the torsion angle of the glycosidic link between the
      sialyl and galactosyl residues and used to select a likely "bound" conformation
      from four low-energy species. Docking the bound form of sialyl Lewis X onto a
      model of the lectin domain of E-selectin suggests that the conformational change
      upon binding results primarily from steric interactions.

PMID- 7521210
TI  - Potentiation of progesterone receptor-mediated transcription by the
      immunosuppressant FK506.
AB  - The nontransformed steroid receptors contain several non-steroid binding
      proteins, such as hsp90, hsp70, and p59. Recently, we and others have shown that
      p59 (FKBP59) is an immunophilin which binds two potent immunosuppressants, FK506
      and rapamycin. This raises the possibility that FK506 or rapamycin may modify the
      function of steroid receptors. To develop this line of inquiry, we chose a yeast
      model system in which the human progesterone receptor form B (hPR-B) was
      cotransformed with a reporter gene. The reporter contains two copies of a
      progesterone response element/glucocorticoid response element (PRE/GRE) upstream
      of the CYC1 promoter which are linked to the lacZ gene of Escherichia coli. We
      found that FK506 potentiated the ability of progesterone in activating
      transcription. To gain insight into the mechanism of FK506's regulation of PR
      action, we questioned whether calcineurin is involved, because it has been shown
      that FK506 is a specific inhibitor of calcineurin, a Ca(2+)- and calmodulin
      regulated phosphatase, through the formation of an FKBP12-FK506-calcineurin
      calmodulin complex. We found that 15-O-desmethyl-FK520, an FK506 analogue which
      is an excellent ligand of FKBP12, but a poor inhibitor of calcineurin, failed to
      induce the same effect as FK506. We also found that calmidazolium, a calmodulin
      antagonist, mimicked FK506's action. Furthermore, immunoblot analysis showed that
      both FK506 and calmidazolium potentiated the effect of progesterone in decreasing
      the mobility of hPR-B upon sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). This suggests that FK506 and calmidazolium may
      cooperate with progesterone in increasing the level of hPR-B
      phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521211
TI  - Human tumor-associated Le(a)-Le(x) hybrid carbohydrate antigen IV3(Gal beta 1-
      >3[Fuc alpha 1-->4]GlcNAc)III3FucnLc4 defined by monoclonal antibody 43-9F:
      enzymatic synthesis, structural characterization, and comparative reactivity with
      various antibodies.
AB  - Two Le(a)-cross-reacting monoclonal antibodies (mAbs) were previously established
      which define complex tumor-associated carbohydrate antigens. The first mAb, 43
      9F, was raised against human squamous cell lung carcinoma and shows preferential
      reactivity with various human cancers over normal cells. Its tumor cell binding
      activity is best inhibited by a milk oligosaccharide characterized as Le(a)-Le(x)
      [Martensson, S., et al. (1988) Cancer Res. 48, 2125], Gal beta 1-->3[Fuc alpha 1-
      >4] GlcNAc beta 1-->3Gal beta 1-->4]Fuc alpha 1-->3]-GlcNAc beta 1-->3Gal beta 1-
      >4Glc (1). The second mAb, ST-421, was raised against human gastric cancer
      xenograft in nude mice and found to have strong tumor growth-suppressing activity
      in nude mice. The epitope recognized by ST-421 was chemically identified as Le(a)
      Le(a), Gal beta 1-->3 [Fuc alpha 1-->4]GlcNAc beta 1-->3Gal beta 1-->3-[Fuc alpha
      1-->4] GlcNAc beta 1-->3Gal beta 1-->4Glc (2) [Stroud, M.R., et al. (1991) J.
      Biol. Chem. 266, 8439]. Both 43-9F and ST-421 cross-react with Le(a).
      Identification of the 43-9F antigen as structure 1 (Le(a)-Le(x)) is tentative
      since it was not based on isolation and chemical characterization of antigen from
      tumor cells or tissues. We therefore synthesized structure 1 starting from sialyl
      nor-hexaosylceramide (VI3NeuAcnLc6), with sequential enzymatic hydrolysis by
      sialidase and beta-galactosidase followed by addition of beta 1-->3Gal with beta
      1-->3 galactosyltransferase. This yielded the hybrid type 1/type 2 chain core
      structure IV3-(Gal beta 1-->3GlcNAc)nLc4, which was fucosylated with alpha 1-
      >3/4 fucosyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521212
TI  - Regulation of the permeability transition pore, a voltage-dependent mitochondrial
      channel inhibited by cyclosporin A.
AB  - Mitochondria from a variety of sources possess a regulated inner membrane
      channel, the permeability transition pore (MTP), which is responsible for the
      'permeability transition', a sudden permeability increase to solutes with
      molecular masses < or = 1500 Da, most easily observed after Ca2+ accumulation.
      The MTP is a voltage-dependent channel blocked by cyclosporin A with Ki in the
      nanomolar range. The MTP open probability is regulated by both the membrane
      potential and matrix pH. The probability of pore opening increases as the
      membrane is depolarized, while it decreases as matrix pH is decreased below 7.3
      through reversible protonation of histidine residues. Many physiological and
      pathological effectors, including Ca2+ and ADP, modulate MTP operation directly
      through changes of the gating potential rather than indirectly through changes of
      the membrane potential (Petronilli, V., Cola, C., Massari, S., Colonna, R. and
      Bernardi, P. (1993) J. Biol. Chem. 268, 21939-21945). Here we present recent work
      from our laboratory indicating that (i) the voltage sensor comprises at least two
      vicinal thiols whose oxidation-reduction state affects the MTP gating potential;
      as the couple becomes more oxidized the gating potential increases; conversely,
      as it becomes more reduced the gating potential decreases; (ii) that MTP opening
      is fully reversible, as mitochondria maintain volume homeostasis through several
      cycles of pore opening/closure; and (iii) that the mechanism of MTP inhibition by
      cyclosporin A presumably involves a mitochondrial cyclophilin but does not
      utilize a calcineurin-dependent pathway.

PMID- 7521213
TI  - Cell partitioning in two-polymer aqueous phase systems and cell electrophoresis
      in aqueous polymer solutions. Human and rat young and old red blood cells.
AB  - It has recently been found that electrophoresis in solutions of appropriately
      selected polymers in phosphate-buffered saline (PBS) can differentiate between
      some closely related cell populations which have identical electrophoretic
      mobilities (EPM) in PBS (e.g., human young and old red blood cells (RBC); RBC
      from Alzheimer patients and normal individuals). The EPM differences detected in
      polymer solutions are most likely a consequence of cell- and polymer-specific
      interactions. Aspects of the relation between the electrophoresis in aqueous
      polymer solutions of native and in vitro treated young and old RBC (from human
      and rat) and their partitioning in a charge-sensitive dextran-poly(ethylene
      glycol) (PEG) aqueous phase system (i.e., a system with a Donnan potential
      between the phases, top phase positive) have been examined further and are
      discussed. Unlike the behavior of RBC from Alzheimer patients and normal
      individuals in which an EPM difference can be detected in PEG solutions but not
      in dextran, differences in EPM between human young and old RBC are detectable in
      solutions of either polymer. Selected enzyme treatments of human young and old
      RBC or their fixation with aldehyde eliminates the EPM differences in dextran;
      while neuraminidase treatment or formaldehyde fixation of rat young and old RBC
      retains EPM differences in dextran between these cells. In these latter cases
      partitioning differences are also in evidence and are in the same direction as
      the cells' relative EPM (i.e., old RBC < young RBC). The earlier hypothesis that
      cell partitioning is 'more sensitive' than cell electrophoresis in detecting
      differences in surface charge between cells bears reexamination because human
      young and old RBC, which cannot be differentiated by single-tube partitioning in
      a charge-sensitive phase system, have different EPM in polymer solutions. The
      difference between these cells can be detected by partitioning but only by use of
      a multiple-extraction procedure. It is then found to be in a direction similar to
      the cells' relative EPM in dextran (i.e., human old RBC > young RBC). Rat young
      and old RBC have different partitions (rat old RBC < young RBC) and different EPM
      (also rat old RBC < young RBC). Thus, while cell partitioning in a charge
      sensitive dextran-PEG aqueous phase system and cell electrophoresis in polymer
      solution seem to reflect, at least with these cell subpopulations, qualitatively
      analogous differences in surface properties (in that increasing partitions and
      EPM are concomitant), there are instances in which either of these physical
      measurements discerns surface differences which escape detection by the other.

PMID- 7521214
TI  - Identification of antigenic sites on the Na+/K(+)-ATPase beta-subunit: their
      sequences and the effects of thiol reduction upon their structure.
AB  - In contrast to the catalytic (alpha) subunit of the Na+/K(+)-ATPase holoenzyme,
      the glycoprotein (beta) subunit has proven to be a poor antigen for monoclonal
      antibody (Mab) production. However, in this work six Mabs directed against the
      beta-subunit of the lamb kidney holoenzyme have been isolated. These Mabs all
      recognize the holoenzyme, but their 'in solution' binding affinities for
      deglycosylated enzyme or isolated beta are generally at least 10-fold higher.
      Species specificity mapping, antibody patterns of binding to beta-fragments and
      competition binding studies indicated that there were only three distinct
      epitopes, with two antibodies binding in the NH2-terminal half (epitopes I and
      II) and 4 Mabs binding at the same or overlapping site (III) in the -COOH
      terminal half of beta. DNA sequence analysis of isolated collections of
      bacteriophage M13 that contain a 15 amino-acid 'epitope library' insert in the
      pIII protein, which enables them to bind to the antibodies, revealed the residues
      KYRDS (amino acids 111-115) and LETYP (amino acids 197-201) to be the deduced
      sequences for the epitopes of Mabs M19-P7-E5 (II) and M17-P5-F11 (III),
      respectively. The epitope I site was not, however, identified. Further studies
      showed that antibody binding to these three determinant sites had no affect on
      the Na+/K(+)-ATPase and K(+)-stimulated p-nitrophenylphosphatase (pNPPase)
      activities of either holoenzyme or deglycosylated enzyme, nor any affect on the
      cation- (Na+, K+ or Mg2+) and ouabain-induced conformational changes monitored
      with FITC-labeled deglycosylated enzyme. Interestingly, anti-beta Mab access to
      the three epitopes was increased following beta-mercaptoethanol inactivation of
      the holoenzyme, but this thiol reduction abolished the binding of two
      conformation-sensitive anti-alpha Mabs to the enzyme. These results are
      consistent with the previous suggestion of Kirley ((1990) J. Biol. Chem. 265,
      4227-4232) that the beta-disulfide linkages not only maintain beta-structure but
      they are critical for maintaining alpha-conformation and holoenzyme activity.

PMID- 7521217
TI  - Enhancement of mRNA synthesis from Marek's disease virus genome in the
      lymphoblastoid cell line, MDCC-MSB1, by 5-azacytidine.
AB  - Marek's disease virus (MDV) DNA in latently infected lymphoblastoid cell lines is
      considerably methylated. A treatment of the MDV-derived lymphoblastoid cell line,
      MDCC-MSB1 (MSB1), with 5-azacytidine (5-AzC) resulted in a hypomethylation of MDV
      DNA and an increase in mRNA from certain portions of the MDV DNA. These results
      suggest methylation of MDV DNA as being one of the factors associated with a
      repression of transcription of MDV DNA in the lymphoblastoid cell line, MSB1.

PMID- 7521216
TI  - Changes of serum amylase, its isozyme fractions and amylase-creatinine clearance
      ratio in dogs with experimentally induced acute pancreatitis.
AB  - To investigate the diagnostic application of amylase to canine pancreatic
      diseases, serum amylase activities, its isozyme fractions and amylase-creatinine
      clearance ratio (ACCR) were analyzed in normal intact dogs and dogs
      experimentally induced acute pancreatitis. There was no statistic difference
      between normal male and female dogs. Amylase specific activities in pancreatic
      tissue extracts were more than 2,300 times higher than that in serum, and were
      also higher than those in other tissues; parotid and mandibular salivary glands,
      lung, heart, liver, spleen, duodenum, jejunum, ileum and kidney. Following the
      chloroform injection into the pancreatic tissue, WBC increased from 6 to 240 hr
      and serum glucose significantly increased at 72 and 96 hr, and no urine glucose
      was detected. BUN as well as serum and urine creatinine showed normal levels.
      ACCR increased until 96 hr without statistic significance. Serum amylase
      activities increased significantly after 3 hr and its isozyme was separated into
      4 fractions (Amy1-Amy4) in contrast to 3 fractions (Amy2-Amy4) in intact dogs.
      Since this extra Amy1 seen from 1 hr increasing after 6 hr similarly to other 3
      fractions, the evaluation of serum amylase and its isozyme fractions was
      indicated to be useful for the diagnosis of acute pancreatitis in dogs.

PMID- 7521215
TI  - Cortical kidney scan evaluation in the follow-up of children with vesico-ureteric
      reflux.
AB  - We present the results obtained in the follow-up of 66 children with vesico
      ureteric reflux (VUR) of different grades (111 refluxing renal units, RU; the VUR
      being bilateral in 47 children), employing the renal cortical agent 99mTc
      aprotinin (TcA). Together with the visual inspection of the scan, we adopted a
      quantitative approach, expressing the results as the split percent uptake of the
      injected dose. The detection of morphological anomalies was more frequent in the
      cases of more severe reflux. Scars were noted in 38 RU, with a higher prevalence
      in more severe grades, except for grade V where severe impairment was more
      frequent. With regard to the amount of functioning parenchyma, the probability of
      a significant loss of nephrons (expressed by a low uptake of TcA), rose with the
      grades, although the higher grades were not invariably associated with
      parenchymal failure. The abnormality detection rate is higher by about 2:1 with
      the TcA scan than with other diagnostic modalities such as i.v. pyelography or
      echography. No differences were found between RU with or without scars as regards
      evolution over time; only when the TcA uptake at presentation was lower than 10%
      was the normal development of the RU likely to be hindered. From these data it
      can be concluded that early diagnosis is the key factor in the management of
      these children with VUR; the morpho-functional assessment with TcA uptake is
      probably the most effective technique for the detection of parenchymal
      abnormalities. In addition, the test has a high prognostic value, an uptake lower
      than 10% indicating an unfavourable prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521218
TI  - Histological difference between retrograde corpora lutea of pregnancy and those
      of estrus in sika deer, Cervus nippon.
AB  - Histological characteristics of retrograde corpora lutea (RCL) were examined for
      105 pairs of ovaries of adult female sika deer, Cervus nippon. Animals were
      captured in various seasons at Mt. Goyo, Iwate Prefecture, the northern part of
      Japan. No histological differences were recognizable between RCL of pregnancy and
      retrograde accessory corpora lutea (RACL), so far as examined by means of
      hematoxylin-eosin and Weigert's resorcin-fuchsin staining. They were both
      irregularly shaped and had well developed arteries in their thick capsules and a
      number of small arteries in the parenchyma. These arteries showed the
      proliferation of elastic fibers showing elastosis in older RCL. The total number
      of these retrograded bodies per female increased with age, suggesting that both
      the retrograded bodies would retain in the ovaries over 7 years. RCL of estrus
      were small hyaline bodies scattered with some degenerated luteal cells in the
      hyaline matrix. They were distinguishable from those of pregnancy since the
      capsule and parenchyma in those of estrus were poorer in blood vessels. RCL of
      estrus appeared in October and November but were rarely seen in February and
      March, suggesting that they will disappear within three months after ovulation.

PMID- 7521220
TI  - [Protein determination by binding with the dye Coomassie brilliant blue G-250].
AB  - Possible applications of the Coomassie brilliant blue G-250 dye method for
      protein assay are reviewed. The physico-chemical and optical properties of the
      dye are considered in detail. The data on the protein-binding mechanism are
      generalized. Modifications of the Coomassie blue G-250 quantitative protein
      assays are critically considered. The applications of the method in medicine,
      biochemistry and biotechnology are discussed.

PMID- 7521219
TI  - Pathologic changes related to subcutaneous implantation of chlormadinone acetate
      for preventing estrus in bitches.
AB  - Pathologic changes related to chlormadinone acetate (CAP) implantation were
      examined using 14 bitches given doses 2.5 to 25 mg/kg for 2 years. Absence of
      corpus luteum in bitches given 5 mg/kg or more supported long-term preventive
      effect of CAP on estrus. The uteri were dose-dependently enlarged and mucometra
      was occasionally found. Endometrial epithelium hyperplasia was observed but less
      in smaller doses. Changes in the mammary gland were only growth and lactation at
      normal degree. No remarkable changes were observed in ACTH and LH cells in the
      pituitary gland. Low, stable levels of CAP maintained in plasma by subcutaneous
      implantation seemed to be the main reason for absence or slight CAP-related
      pathologic changes.

PMID- 7521221
TI  - [Dynamics of antibody formation, isotypes and specificity of antibodies in the
      immune response of Balb/c mice to cytochrome c].
AB  - The production of IgG antibody (Ab) to cytochrome c in BALB/c mice reached its
      maximum four weeks after primary immunization which is significantly later than
      the response to the same dose of keyhole limpet hemocyanin (KLH). The relative
      amounts of IgG subclasses varied during the immune response to KLH: IgG2a Abs
      dominating on day 11 were replaced by IgG1 on day 30 after immunization. This was
      not the case with anti-cytochrome c Abs: their IgG subclasses varied
      significantly among individual mice within the strain. The heme elimination
      altered the cytochrome c antigenic structure, although some antigenic
      determinants remained intact. The heme with its neighbouring residues represented
      by heme peptide 14-22 was not recognized by anti-cytochrome c Abs. Serum IgG Abs
      interacted with peptides 1-65 and 1-80 obtained by BrCN hydrolysis of cytochrome
      c; however, they did not bind to peptide 66-104. The Abs affinity purified on
      cytochrome c bound to peptides 1-65 and 1-80, while the Abs purified on peptide 1
      65 or apo-cytochrome could recognize native cytochrome c as well.

PMID- 7521222
TI  - The influence of induction chemotherapy and remission status on haemostasis in
      patients treated for acute myeloid leukaemia.
AB  - Haemostatic parameters were studied in 31 adult patients treated for acute
      myeloid leukaemia (AML) using the 3 + 7 regimen. Lower values of antithrombin III
      (AT-III), alpha 2-antiplasmin (alpha 2AP) and plasminogen were observed on days 8
      and 14 (P < 0.05). Fibrinopeptide A (FpA) levels were higher at diagnosis (P <
      0.05), increased again during chemotherapy on days 4 and 8 and eventually
      returned to the normal range. Tissue plasminogen activator, plasminogen activator
      inhibitor, protein C and fibrin(ogen) degradation products were normal throughout
      the period of observation. Complete remission (CR) was achieved in 19 of 31
      patients (61%). In order to compare haemostatic changes in CR patients with those
      in refractory cases, patients were divided into two groups. In patients with
      refractory AML (n = 12) AT-III, plasminogen and alpha 2 AP were significantly
      lower than in those in CR. FpA levels were increased in all patients at
      diagnosis. This elevation progressed in both groups during chemotherapy (on days
      4 and 8) and then normalized only in patients in CR. However, in resistant
      patients, higher FpA values persisted or even increased further on day 14. The
      fact that none of our patients suffered from clinically manifest thrombotic
      complications suggested that haemostasis was well compensated and the observed
      changes were of no clinical importance, even if they were significant
      statistically.

PMID- 7521224
TI  - Asymmetric gramicidin channels: heterodimeric channels with a single F6Val1
      residue.
AB  - Substitution of Val1 by 4,4,4,4',4',4'-F6Val in [Val1]gramicidin A ([Val1]gA)
      produces channels in which the effects of amino acid replacements on dimer
      stability and ion permeation are nonadditive. If only one Val1 (in a symmetric
      [Val1]gA channel) is substituted by F6Val, the resulting heterodimeric channels
      are destabilized relative to both homodimeric parent channels and the single
      channel conductance of the heterodimeric channels is reduced relative to the
      parent channels (Russell, E. W. B., L. B. Weiss, F. I. Navetta, R. E. Koeppe II,
      and O. S. Andersen. 1986. Single-channel studies on linear gramicidins with
      altered amino acid side chains. Effects of altering the polarity of the side
      chain at position #1 in gramicidin A. Biophys. J. 49:673; Durkin, J. T., R. E.
      Koeppe II, and O. S. Andersen. 1990. Energetics of gramicidin hybrid channel
      formation as a test for structural equivalence. Side-chain substitutions in the
      native sequence. J. Mol. Biol. 211:221-234). To understand the basis for this
      destabilization, we have examined further the characteristics of
      [F6Val1]/[Xxx1]gA heterodimers, where Xxx = Gly, Val, and Ala. These
      heterodimeric channels show rapid current transitions between (at least) two
      current levels and display asymmetric i-V characteristics. The orientation of the
      heterodimers relative to the applied potential was determined by asymmetric
      addition of the gramicidin analogs, one to each side of a preformed bilayer. The
      current transitions are most clearly illustrated for [F6Val1]/[Gly1]gA
      heterodimers, which possess two finite and well defined current levels. Based on
      the existence of these two conductance states and the analysis of duration and
      interval distributions, we conclude that the transitions between the two current
      levels correspond to conformational transitions in "stable" heterodimers. In the
      case of [F6Val1]/[Val1]gA and [F6Val1]/[Ala1]gA heterodimers, the low-conductance
      state is indistinguishable from zero. The two (or more) conductance states
      presumably correspond to different orientations of the dipolar F6Val1 side chain.
      The distribution between the high- and the low-conductance states varies as a
      function of potential in [F6Val1]/[Gly1]gA channels. These characteristics cause
      the [F6Val1]/nonpolar (Val, Ala, Gly)gA hybrid channels to serve as a "simple"
      model for understanding gating transitions in membrane-spanning channels.

PMID- 7521225
TI  - Reversible and irreversible effects of basic peptides on the mitochondrial
      cationic channel.
AB  - We have previously shown that a 13-residue basic peptide, derived from the
      presequence of a mitochondrial precursor, blocked the cationic channel of the
      outer mitochondrial membrane. The properties of the blockade suggested that the
      peptide could go through the pore in the presence of a sufficient driving force.
      In an attempt to evaluate more precisely the relevance of such an interpretation,
      we have examined the effect on the same channel of basic peptides from 16 to 34
      residues, most of which are parts of or derive from mitochondrial presequences.
      Two peptides were found to induce a reversible voltage-dependent blockade, the
      properties of which were the same as those of the blockade induced by the 13
      residue peptide. The others had a similar effect, but triggered in addition a
      modification of the voltage gating that persisted after washing the peptide out.
      The modification was in turn abolished by trypsin added to the side of the
      channel previously exposed to the peptide. The protease acted on the bound
      peptide and not on the channel itself. The irreversible modification of the
      voltage gating, the mechanism of which remains obscure, was not specific for
      mitochondrial-addressing sequences.

PMID- 7521223
TI  - Modeling large RNAs and ribonucleoprotein particles using molecular mechanics
      techniques.
AB  - There is a growing body of low-resolution structural data that can be utilized to
      devise structural models for large RNAs and ribonucleoproteins. These models are
      routinely built manually. We introduce an automated refinement protocol to
      utilize such data for building low-resolution three-dimensional models using the
      tools of molecular mechanics. In addition to specifying the positions of each
      nucleotide, the protocol provides quantitative estimates of the uncertainties in
      those positions, i.e., the resolution of the model. In typical applications, the
      resolution of the models is about 10-20 A. Our method uses reduced
      representations and allows us to refine three-dimensional structures of systems
      as big as the 16S and 23S ribosomal RNAs, which are about one to two orders of
      magnitude larger than nucleic acids that can be examined by traditional all-atom
      modeling methods. Nonatomic resolution structural data--secondary structure,
      chemical cross-links, chemical and enzymatic footprinting patterns, protein
      positions, solvent accessibility, and so on--are combined with known motifs in
      RNA structure to predict low-resolution models of large RNAs. These structural
      constraints are imposed on the RNA chain using molecular mechanics-type potential
      functions with parameters based on the quality of experimental data. Surface
      potential functions are used to incorporate shape and positional data from
      electron microscopy image reconstruction experiments into our models. The
      structures are optimized using techniques of energy refinement to get RNA folding
      patterns. In addition to providing a consensus model, the method finds the range
      of models consistent with the data, which allows quantitative evaluation of the
      resolution of the model. The method also identifies conflicts in the experimental
      data. Although our protocol is aimed at much larger RNAs, we illustrate these
      techniques using the tRNA structure as an example and test-bed.

PMID- 7521226
TI  - Intramolecular and intermolecular enzymatic modulation of ion channels in excised
      membrane patches.
AB  - A calcium-activated potassium channel in posterior pituitary nerve terminals was
      modulated by phosphorylation and dephosphorylation. Nearly every patch of
      membrane containing this channel also contained both membrane bound protein
      phosphatase and membrane-bound protein kinase. By examining the statistical and
      kinetic nature of phosphorylation and dephosphorylation in excised patches, it
      was possible to evaluate two contrasting models for these enzymatic reactions.
      One of these models treated catalysis as an intermolecular process in which the
      enzyme and substrate are separate molecular species that diffuse and encounter
      one another during collisions. The second model treated catalysis as an
      intramolecular process in which the enzyme and substrate reside within a stable
      macromolecular complex. The study began with a Poisson analysis of the
      distribution of channel number in patches, and of the number of protein
      phosphatase-free and protein kinase-free patches. Subsequent kinetic analysis of
      dephosphorylation yielded an estimate of the mean number of protein phosphatase
      molecules per patch that was similar to the value obtained from Poisson analysis.
      Because these two estimates were independent predictions based on the
      intermolecular model, their agreement supported this model. Analysis of channel
      number in protein phosphatase-free patches and of the rarity of patches showing
      partial but incomplete rundown provided additional support for the intermolecular
      model over the intramolecular model. Furthermore, dephosphorylation exhibited
      monotonic kinetics with a rate well below the diffusion limit. Thus, several
      different lines of analysis support the intermolecular model for
      dephosphorylation, in which the protein phosphatase must encounter its substrate
      to effect catalysis. In contrast to the monotonic kinetics of dephosphorylation,
      the phosphorylation reaction exhibited sigmoidal kinetics, with a rate that
      depended on membrane potential. Voltage dependence is an unlikely property for a
      kinetic step involving encounters resulting from diffusion. Furthermore, the
      velocity of the phosphorylation reaction exceeded the diffusion limit, and this
      observation is inconsistent with the intermolecular model. Thus, both
      intermolecular and intramolecular enzymatic mechanisms operate in the modulation
      of the calcium-activated potassium channel of the posterior pituitary. These
      studies provide a functional characterization of the interactions between enzyme
      and substrate in intact patches of cell membrane.

PMID- 7521228
TI  - Can the stereoselective effects of the anesthetic isoflurane be accounted for by
      lipid solubility?
AB  - Isoflurane is an inhalational general anesthetic widely used in surgical
      operations as a racemic mixture of its two optical isomers. The recent
      availability of pure enantiomers of isoflurane has encouraged their use in
      experimental studies, and stereoselective effects have now been observed on
      anesthetic-sensitive neuronal ion channels. Although it has been assumed that
      such chiral effects demonstrate direct interactions with proteins, it is possible
      that they could be due to stereoselective interactions with chiral membrane
      lipids. We have determined the partition coefficients of the two optical isomers
      of isoflurane between lipid bilayers and water, using racemic isoflurane and gas
      chromatography with a chiral column. For lipid bilayers of phosphatidylcholine
      (PC) and 4 mol% phosphatidic acid (PA), both with and without cholesterol (CHOL),
      we found equal partitioning of the isoflurane optical isomers. The ratios of the
      S(+) to R(-) isoflurane partition coefficients were (mean +/- SEM): 1.018 +/-
      0.010 for bilayers of PC/CHOL/PA (mole ratios 56:40:4) and 1.011 +/- 0.002 for
      bilayers of PC/PA (mole ratio 96:4). Molar partition coefficients for racemic
      isoflurane were 49 +/- 4 and 165 +/- 10, respectively. These findings support the
      view that the stereoselective effects on ion channels observed with isoflurane
      are due to direct actions on proteins rather than lipids.

PMID- 7521227
TI  - Connexin37 forms high conductance gap junction channels with subconductance state
      activity and selective dye and ionic permeabilities.
AB  - Gap junctions are thought to mediate the direct intercellular coupling of
      adjacent cells by the open-closed gating of an aqueous pore permeable to ions and
      molecules of up to 1 kDa or 10-14 A in diameter. We symmetrically altered the
      ionic composition or asymmetrically added 6-carboxyfluorescein (6-CF, M(r) =
      376), a fluorescent tracer, to pairs of connexin37-transfected mouse neuro2A
      cells to examine the ionic and dye permeability of human connexin37 channels. We
      demonstrate that the 300-pS channel formed by connexin37 has an effective
      relative anion/cation permeability ratio of 0.43, directly converts to at least
      one intermediate (63 pS) subconductance state, and that 6-CF dye transfer is
      accompanied by a 24% decrease in unitary channel conductance. These observations
      favor a new interpretation of the gap junction pore consistent with direct ion
      channel interactions or electrostatic charge effects common to more conventional
      multistate ion channels. These results have distinct implications about the
      different forms of intercellular signaling (cationic, ionic, and/or biochemical)
      that can occur depending on the expression and conformation of the connexin
      channel proteins.

PMID- 7521229
TI  - Dynamics of neutrophil rolling over stimulated endothelium in vitro.
AB  - Prior to extravasation at sites of acute inflammation, neutrophils roll over
      activated endothelium. Neutrophil rolling is often characterized by the average
      rolling velocity. An additional dynamic feature of rolling that has been
      identified but not extensively studied is the fluctuation in the rolling velocity
      about the average. To analyze this characteristic further, we have measured the
      instantaneous velocity of bovine neutrophils interacting with lipopolysaccharide
      stimulated bovine aortic endothelium at shear stresses of 1, 2, 3, and 4
      dynes/cm2. The average velocities are quantitatively similar to those reported
      for human neutrophils rolling over reconstituted P-selectin at a surface density
      of 400 sites/microns 2. At all shear stresses tested, the population average
      variance in the instantaneous velocity is at least 2 orders of magnitude higher
      than the theoretical variance generated from experimental error, indicating that
      the neutrophils translate with a nonconstant velocity. Possible sources of the
      variance are discussed. These include "macroscopic" sources such as topological
      heterogeneity in the endothelium and microscopic sources, such as inherent
      stochastic formation and breakage of the receptor-ligand bonds that mediate the
      rolling. Regardless of the ultimate source of the variance, these results justify
      the use of mathematical models that incorporate stochastic processes to describe
      bond formation and breakage between the neutrophil and the endothelium and hence
      are able to generate variable velocity trajectories.

PMID- 7521230
TI  - Activation of the liver carcinogen 2-nitropropane by aryl sulfotransferase.
AB  - 8-Aminoguanine had previously been identified as one of the nucleic acid base
      modifications produced in livers of rats by treatment with the hepatocarcinogen 2
      nitropropane (2-NP), and a hypothetical mechanism of activation of 2-NP to
      hydroxylamine-O-sulfonate or acetate that would lead to NH2+, an aminating
      species, was proposed [Sodum et al. (1993) Chem. Res. Toxicol. 6, 269-276]. We
      now present in vivo and in vitro experimental evidence for the activation of 2-NP
      to an aminating species by rat liver aryl sulfotransferase. Pretreatment of rats
      with the aryl sulfotransferase inhibitors pentachlorophenol or 2,6-dichloro-4
      nitrophenol significantly decreased the levels of liver nucleic acid
      modifications produced by 2-NP treatment. Furthermore, partially purified rat
      liver aryl sulfotransferase was shown to activate 2-NP and 2-NP nitronate in
      vitro at neutral pH and 37 degrees C, to a reactive species that aminated
      guanosine at the C8 position. This activation was dependent on the presence of
      the enzyme, its specific cofactor adenosine 3'-phosphate 5'-phosphosulfate, and
      mercaptoethanol. As in the case of the in vitro studies, pentachlorophenol and
      2,6-dichloro-4-nitrophenol inhibited the in vitro formation of 8-aminoguanosine
      and 8-oxoguanosine. The corresponding primary nitroalkane, 1-nitropropane, which
      is not mutagenic and does not appear to be carcinogenic, was not a substrate for
      aryl sulfotransferase in the in vitro amination of guanosine.

PMID- 7521231
TI  - Complex patterns of expression suggest extensive roles for the alpha 2 beta 1
      integrin in murine development.
AB  - The extracellular matrix plays important roles in embryogenesis. The integrin
      family of adhesion receptors may mediate critical cellular interactions with the
      extracellular matrix during development. In this study, we elucidated the
      developmental spatial and temporal expression pattern of the alpha 2 beta 1
      integrin heterodimer, a cell surface receptor for collagens and laminin. We
      generated reagents for studying the alpha 2 beta 1 integrin and examined the
      developmental expression of the integrin in postimplantation mice. A partial
      length murine alpha 2 cDNA was isolated and the protein encoding region was found
      to be 82% homologous to that of the human alpha 2 cDNA. A synthetic peptide
      corresponding to the carboxy-terminus of murine alpha 2 was used to generate
      alpha 2-specific antiserum. The antiserum and riboprobes derived from both the
      alpha 2 cDNA and the previously characterized murine beta 1 subunit cDNA were
      used to determine the spatiotemporal expression of the alpha 2 subunit by
      immunocytochemistry and of the alpha 2 and beta 1 mRNAs by in situ hybridization.
      Both approaches gave concordant results. Expression of the alpha 2 integrin
      subunit was observed in both the maternal and embryonic components of the
      placenta, namely the perivascular and basal zone decidual cells and decidual
      cells and spongiotrophoblasts at the maternal/embryonic junction. Expression was
      also observed in cells actively producing and remodeling the extracellular matrix
      in the maternal uterus and in the developing gut, lens, cartilage, bone, and
      tooth of the embryo. Generally, expression of the alpha 2 integrin subunit was
      found in cells entering their later stages of differentiation such as in
      chondrocytes as they became hypertrophic, ameloblasts and odontoblasts as they
      became columnar and began to secrete the matrix of the tooth, endothelial cells
      after they formed tubules, in the lens just prior to and during lens fiber
      production, and in the collecting ducts of the kidney only after full gestation.
      Throughout embryogenesis, beta 1 mRNA was widely distributed and present in cell
      types expressing alpha 2 mRNA and protein. The developmental expression pattern
      of the alpha 2 beta 1 integrin suggests roles for the integrin in placental
      development and matrix assembly and remodeling.

PMID- 7521232
TI  - Lymphomatoid papulosis and Hodgkin's disease: report of a case.
AB  - The authors report the case of a 67-year-old-man who presented with stage IIIAa
      Hodgkin's disease (HD) almost 17 years after developing CD30+ type A lymphomatoid
      papulosis (LP). Combination chemotherapy resulted in a complete remission of the
      HD for 2 years, although the LP continued relentlessly as before. A possible link
      between HD and LP is discussed in the light of similar cases reported in the
      literature.

PMID- 7521233
TI  - Antiarrhythmic agents in older patients. Current state of knowledge.
AB  - The treatment of ventricular arrhythmias in the elderly population is a
      challenging problem. Elderly patients are more predisposed to arrhythmias, are
      less responsive to antiarrhythmic agents and are more susceptible to the adverse
      effects of antiarrhythmic agents. Results from recent trial have altered the
      general approach to management of ventricular arrhythmias. The results of the
      Cardiac Arrhythmia Suppression Trials (CAST I and II) exemplified the
      disappointing results from numerous other studies, revealing the overall lack of
      efficacy of class I agents in reducing mortality in patients with coronary artery
      disease and asymptomatic premature ventricular complexes (PVCs). The results of
      CAST I and II also demonstrated the higher likelihood of older patients
      developing ventricular arrhythmias and toxicity to antiarrhythmic agents.
      Combined results of these studies have discouraged empirical antiarrhythmic
      therapy, especially in older patients with asymptomatic PVCs. In contrast,
      secondary prevention trials with beta-blockers in post-myocardial infarction
      patients have shown definitive survival benefit and reduction in ventricular
      arrhythmias, especially in the older patient population. Smaller trials with
      amiodarone have also shown survival benefit in post-myocardial infarction
      patients with or without PVCs. Management of ventricular tachycardia and
      fibrillation has become less empirical and more systematic with use of
      electrophysiologically guided and/or Holter monitor-guided therapy. Sotalol and
      amiodarone are especially effective agents. The efficacy of implantable
      cardioverter/defibrillators are also being compared with medical therapy
      systematically in multicentre trials. In general, empirical antiarrhythmic
      therapy is discouraged especially in the treatment of asymptomatic PVCs and
      should be reserved for systematic use in life-threatening arrhythmias.

PMID- 7521236
TI  - [Ulcerative breast neoplasm].

PMID- 7521237
TI  - [The clinical and therapeutic characteristics of a neoplasm of the left superior
      colon].
AB  - As "CSS" the authors name the left segment (1/3) of the transverse colon with the
      splenic angle and fixed segment of the left colon. The author's conclusion of a
      retrospective analysis upon 34 neoplasms situated in this colonic area is the
      fact that there are enough arguments to treat them as a unitary group. From the
      anatomic point of view these arguments are the common vessels and lymphatics
      reports, and from the clinical point of view these neoplasms have in common the
      symptomatology (generally the diagnostic is established later on) and a great
      tendency of a loco-regional invasion which generate severe complications. The
      surgical treatment with oncologic radical intervention is the same for any
      primary neoplasm localization (within the there segments of "CSS"). Multi
      visceral resections are frequently necessary too.

PMID- 7521238
TI  - Prognostic value of immunophenotypic characteristics of blast cells in acute
      myeloid leukemia.
AB  - In order to elucidate the prognostic role of cytofluorimetry analysis of leukemic
      cells in AML, the immunophenotypic characteristics of blast cells obtained from
      66 AML patients belonging to M0-M2 and M4-M5 FAB subtypes have been investigated
      by flow cytometry using a large panel of monoclonal antibodies (McAbs) utilized
      in single, double, and triple fluorescence experiments. On a univariate analysis,
      four different immunophenotypic blast cell characteristics were found to be
      associated with a poor prognosis: expression of CD34 "bright" (ratio > 10 between
      fluorescence emission of positive cells and that of negative (isotypic) control
      P/N ratio: mean MESF value: 265,000) in > 15% blast cells, co-expression of CD34
      and CD33 in > 60% blast cells, expression of CD14 in > 30% leukemic cells, the
      MDR+ ("multiple drug resistant") phenotype. In contrast, the duration of
      remission, and overall survival of AML patients showing a "dim" CD34 expression
      (P/N ratio: 3-10: mean MESF value: 49,000) was similar to that of CD34- AML
      patients, irrespective of the percentage of positivity for CD34, which was,
      however, a predictive factor of survival in patients with higher CD34
      fluorescence intensities in their blastic population. No correlation between FAB
      subtypes, prognosis and immunophenotype was found. The multivariate regression
      analysis showed that, besides age, only the combined expression of CD34 and CD33
      had independent prognostic meaning. Indeed, in each FAB subtypes the CD34+/CD33+
      phenotype was associated with a shorter survival and a lower mitotic rate. These
      data may contribute to the understanding of the discrepancies so far observed in
      the literature regarding the prognostic role played by the CD34 expression on
      leukemic AML blasts.

PMID- 7521235
TI  - The inducible nitric oxide synthase gene, Nos2, maps to mouse chromosome 11.

PMID- 7521239
TI  - Molecular control of B lymphocyte growth and differentiation.
AB  - During antigen driven immune responses, antigen-specific naive B lymphocytes
      undergo a cascade of events including activation, expansion, mutations, isotype
      switch, selections and differentiation into either antibody secreting plasma
      cells or memory B cells. These antigen-dependent events, which we propose to call
      immunopoiesis, occur in different areas of secondary lymphoid organs, as well as
      other nonlymphoid organs. B cells interact with antigens and numerous cell types
      (T cells, dendritic cells, follicular dendritic cells and macrophages) through
      numerous cell surface molecules and cytokines. B cells costimulated through their
      antigen receptor and cytokines such as interleukin 2 (IL-2), IL-4 and IL-10
      undergo limited proliferation and differentiation into immunoglobulin (Ig)
      secreting cells. In contrast, crosslinking of the B cell CD40 antigen, a member
      of the tumor necrosis factor (TNF) receptor family, results in major cellular
      activation further modulated by cytokines. In particular, IL-4 and IL-13 permit
      establishment of long-term factor-dependent B cell lines, as well as isotype
      switch towards the production of IgE and IgG4. Addition of IL-10 to CD40
      activated B cells results in limited proliferation and remarkable differentiation
      into plasma cells. IL-10 also participates in isotype switch towards IgG1, IgG3
      and IgA. The ligand for CD40, a member of the TNF family, is transiently
      expressed on activated T cells, and interrupted CD40/CD40-L interactions result
      in profoundly altered humoral immune responses.

PMID- 7521240
TI  - A quantitative assay that evaluates the capacity of human stromal cells to
      support granulomonopoiesis in situ.
AB  - We describe an assay that makes possible the observation of granulomonocytic
      colonies grown on allogeneic stromal layers and the quantification of the stroma
      adherent colony-forming cells (CFC). Stromal layers were generated from Stro-1
      positive cells isolated from adherent layers of primary long-term marrow cultures
      using magnetic beads coated with the Stro-1 antibody. The stromal layers
      consisted mainly of myofibroblastic cells. Marrow fractions depleted of cells
      bearing receptors for soybean agglutinin (SBA) and enriched in CD34+ cells were
      obtained by panning. SBA-, CD34+ marrow cells were seeded onto stromal cells
      grown in 96-well plates. After four weeks, a mixture of cytokines was added
      (granulocyte-macrophage colony-stimulating factor [GM-CSF]: 25 U/ml, interleukin
      [IL]-3: 4 ng/ml, Steel factor: 5 ng/ml and growth factors provided by 3%
      conditioned medium from the 5637 cell line). Wells with large colonies
      (containing 10(3) to 10(4) cells) were scored after 14 days. Limiting dilution
      analysis of data revealed a Poisson distribution of the stroma-adherent CFC.
      There was an average of one stroma-adherent CFC per 167 CD34+ enriched marrow
      cells, which gave an estimated frequency of one CFC per 10(5) unfractionated bone
      marrow cells. Colonies contained cells that gave rise to CFU-GM after replating
      in agar (5-40 CFU-GM were provided per each stroma-adherent CFC), but not cells
      with self-renewal ability (as indicated by negative results after replating
      single colonies onto secondary adherent layers). Colonies usually formed from a
      cobblestone-area and developed in intimate contact with alpha SM actin positive
      stromal cells. Some of the stromal cells were located above granulocytic cells,
      corresponding to the description of "blanket cells." This assay should allow the
      study of colony-formation on marrow stroma without disrupting the hemopoietic
      niche.

PMID- 7521234
TI  - Tacrine. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic efficacy in Alzheimer's disease.
AB  - Tacrine is a centrally acting cholinesterase inhibitor with additional
      pharmacological activity on monoamine levels and ion channels. It has been
      postulated that some or all of these additional properties may also be relevant
      to the mode of action of the drug. There are wide interindividual variations in
      pharmacological and clinical response to tacrine, possibly related to
      interindividual variation in bioavailability. Tacrine appears to improve
      cognitive function and behavioural deficits in a proportion of patients with
      Alzheimer's disease, at dosages of 80 to 160 mg/day. In the best designed trials,
      30 to 51% of evaluable patients showed an improvement of at least 4 points on the
      cognitive subscale of the Alzheimer's Disease Assessment Scale, versus 16 to 25%
      of placebo recipients. A similar proportion of tacrine recipients were judged to
      have improved when global assessment scales were used. There was a significant
      dose-response relationship up to 160 mg/day. However, large numbers of patients
      were withdrawn during the trials, many because of tacrine-associated increases in
      transaminase levels. Elevated liver enzyme levels occurred in about 50% of
      tacrine recipients (reaching clinical significance in about 25%). Cholinergic
      symptoms also occurred more often in tacrine recipients than in those receiving
      placebo. A gradual increase in tacrine dosage, at 6-week intervals, is
      recommended when initiating therapy, and weekly serum transaminase monitoring is
      required for 6 weeks after each dosage increase. Despite the limitations implied
      by the low proportion of responders and high incidence of hepatic adverse effects
      associated with therapy, tacrine appears to make a measurable difference in both
      cognitive and behavioural function in a proportion of patients with Alzheimer's
      disease--a welcome advance in an area previously devoid of acceptable treatment
      options.

PMID- 7521241
TI  - Expression of adhesion molecules on human hematopoietic progenitor cells at
      different maturational stages.
AB  - In this report we examined the expression of several adhesion molecules on human
      hematopoietic progenitor cells at different maturational stages. Human
      hematopoietic progenitor cell-enriched fractions were prepared from bone marrow
      cells by depleting lymphocytes and monocytes (CD2+, CD14+ and CD19+ cells). These
      cells were separated into adhesion molecule-positive and -negative cell
      populations by immunomagnetic separation methods and then assessed for their
      ability to form various colony forming cells (CFC). CD44 and CD49d were expressed
      on multipotent hematopoietic progenitor cells, or mixed colony forming units (CFU
      Mix), erythroid burst forming units (BFU-E), granulocyte-macrophage CFU (CFU-GM)
      and erythroid CFU (CFU-E). Leu8 was expressed on CFU-Mix, BFU-E and some
      populations of CFU-GM, but not CFU-E. CD11a was expressed on some populations of
      CFU-Mix, CFU-GM and BFU-E. CD54 was expressed only on some populations of CFU-GM.
      These results suggest that Leu8, CD44, CD49d and CD11a appear to play important
      roles in the differentiation and proliferation of human hematopoietic progenitor
      cells at different maturational stages in the bone marrow microenvironment.

PMID- 7521242
TI  - In vivo stimulation of neutrophil function by lenograstim (glycosylated rHuG-CSF)
      in oncohematologic patients: results of a phase I trial.
AB  - The aim of this work was to study the evolution of neutrophil functions in non
      neutropenic cancer patients. Thirty non-neutropenic patients, median age 35 years
      (range 19-52), with solid tumors (n = 21) or lymphomas (n = 9) entered a phase I
      study of five days of s.c. (n = 24) or i.v. bolus (n = 6) lenograstim,
      recombinant human glycosylated granulocyte colony-stimulating factor (rHuG-CSF
      Chugai-Rhone-Poulenc), with dose escalation from 1 to 40 micrograms/kg/day.
      Neutrophil functions were studied before lenograstim (D1) and 24 h after the last
      dose (D6). Granulocyte count rose in a significant way, and enzyme release,
      phagocytosis and bacterial killing were stimulated. All patients had improvement
      of at least one neutrophil function. Directed migration was depressed, although
      it was still in the normal range. These findings confirm that lenograstim is a
      potent activator of neutrophil functions in non-neutropenic cancer patients and
      may be useful as an adjunct to conventional antimicrobial therapy.

PMID- 7521243
TI  - Stimulatory effect of human insulin on erythroid progenitors (CFU-E and BFU-E) in
      human CD34+ separated bone marrow cells and the relationship between insulin and
      erythropoietin.
AB  - Erythropoietin is known to be effective for the treatment of anemia in chronic
      renal failure, but the efficacy of erythropoietin for anemia in other diseases is
      not so great. Insulin exerts a growth promoting activity in various kinds of
      cells. In the present study, the effects of insulin on erythroid progenitors
      (colony forming units-erythroid, CFU-E; and burst forming units-erythroid, BFU-E)
      in human bone marrow were examined at various concentrations of recombinant human
      erythropoietin (rh-Epo) to clarify the relationship between erythropoietin and
      insulin. Human insulin stimulated the formation of CFU-E and BFU-E in the
      presence of three concentrations (0.25, 5, and 100 U/ml) of rh-Epo. Stimulatory
      effects of human insulin on CFU-E and BFU-E were also observed in the
      nonphagocytic and nonadherent bone marrow fraction (NP-NA fraction) and in the NP
      NA and T cell-depleted fraction at each concentration of rh-Epo. Human insulin
      further stimulated the CFU-E and BFU-E growth in CD34+ separated bone marrow
      cells. These results indicate that the enhancing effect of human insulin on
      erythroid progenitors is not mediated through monocytes and macrophages or T
      cells, suggesting a direct action on erythroid progenitors.

PMID- 7521244
TI  - [Churg-Strauss syndrome does not respond to immunosuppressive treatment].
AB  - A case of 35-years old woman with Churg-Strauss syndrome was presented. The
      appropriate diagnosis was established on the typical clinical history and
      microscopic studies. Clinical observation revealed a short-term improvement after
      immunosuppressive therapy.

PMID- 7521245
TI  - A methyl green-pyronin technique for demonstrating cell death in the murine
      tumour S180.

PMID- 7521246
TI  - No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of
      insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with
      spinal osteoporosis.
AB  - To test the hypothesis that a dysfunctional growth hormone (GH)-insulin-like
      growth factor (IGF) axis may play a role in the pathogenesis of osteoporosis, we
      compared the levels of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3) in 15
      women with spinal osteoporosis (i.e. at least one non-traumatic vertebral
      fracture) and 15 normal age-matched women. Furthermore, the response to 3 days'
      treatment with recombinant human GH (r-hGH) (0.2 IU kg-1.day-1) was determined.
      The basal levels of IGF-I, IGF-II and IGFBP-3 were similar in patients and
      controls (mean +/- SEM): IGF-I, 16.5 +/- 1.3 versus 16.0 +/- 1.3 nmol/l (NS); IGF
      II, 79.9 +/- 3.6 versus 72.5 +/- 4.1 nmol/l (NS); and IGFBP-3, 125.7 +/- 6.5
      versus 130.3 +/- 7.8 nmol/l (NS). Stimulation with r-hGH elicited increased
      levels of IGF-I, IGF-II and IGFBP-3 within both groups (p < 0.001). The maximal
      values expressed as a percentage of baseline were: IGF-I, 341 +/- 26% versus 369
      +/- 22%, IGF-II, 125 +/- 4% versus 119 +/- 5%, IGFBP-3, 141 +/- 5% versus 147 +/-
      7% in osteoporotic patients and controls, respectively. No significant
      differences were observed between patients and controls in either their maximal
      response or in the area under the response curves. Our results do not support the
      hypothesis of a dysfunctional GH-IGF axis in women with spinal osteoporosis.

PMID- 7521247
TI  - GDP-mannose dehydrogenase is the key regulatory enzyme in alginate biosynthesis
      in Pseudomonas aeruginosa: evidence from metabolite studies.
AB  - The Pseudomonas aeruginosa enzyme GDP-mannose dehydrogenase (GMD) is encoded by
      the algD gene, and previous genetic studies have indicated that it is a key
      regulatory and committal step in the biosynthesis of the polysaccharide alginate.
      In the present study the algD gene has been cloned into the broad-host-range
      expression vector pMMB66EH and GMD overexpressed in mucoid and genetically
      related non-mucoid strains of P. aeruginosa. The metabolic approach of P. J.
      Tatnell, N. J. Russell & P. Gacesa (1993), J Gen Microbiol 139, 119-127, has been
      used to investigate the subsequent effect of GMD overexpression on the
      intracellular concentrations of the key metabolites GDP-mannose and GDP
      mannuronate, which have been related to GMD activity and total alginate
      production. The overexpression of algD in mucoid and non-mucoid strains resulted
      in elevated GMD activities compared to wild-type strains; there was a concomitant
      reduction in GDP-mannose concentrations and greatly increased GDP-mannuronate
      concentrations. However, significantly, alginate biosynthesis was detected only
      in mucoid strains and GMD overexpression resulted in only a marginal increase in
      exopolysaccharide production. The GDP-mannuronate concentrations in mucoid
      strains which overexpressed GMD were always significantly greater than those of
      GDP-mannose, indicating that GMD was no longer the major kinetic control point in
      the biosynthesis of alginate by these genetically-manipulated strains. The small
      but significant increase in alginate production by such strains together with the
      increased GDP-mannuronate concentrations is interpreted as meaning that a later
      enzyme of the alginate pathway has become the major kinetic control point and now
      determines the extent of alginate production. This study has provided direct
      metabolic evidence that GMD is the key regulatory enzyme in alginate biosynthesis
      in P. aeruginosa.

PMID- 7521248
TI  - Nucleotide sequences of the spacer-1, spacer-2 and trailer regions of the rrn
      operons and secondary structures of precursor 23S rRNAs and precursor 5S rRNAs of
      slow-growing mycobacteria.
AB  - The single ribosomal RNA (rrn) operons of slow-growing mycobacteria comprise the
      genes for 16S, 23S and 5S rRNA, in that order. PCR methodology was used to
      amplify parts of the rrn operons, namely the spacer-1 region separating the 16S
      rRNA and 23S rRNA genes and the spacer-2 region separating the 23S rRNA and 5S
      rRNA genes of Mycobacterium avium, Mycobacterium intracellulare, 'Mycobacterium
      lufu' and Mycobacterium simiae. The amplified DNA was sequenced. The spacer-2
      region, the 5S rRNA gene, the trailer region and the downstream region of the rrn
      operon of Mycobacterium tuberculosis were cloned and sequenced. These data,
      together with those obtained previously for Mycobacterium leprae, were used to
      identify putative antitermination signals and RNase III processing sites within
      the spacer-1 region. Notable features include two adjacent potential Box B
      elements and a Box A element. The latter is located within a sequence of 46
      nucleotides which is very highly conserved among the slow-growers which were
      examined. The conserved sequence has the capacity to interact through base
      pairing with part of the spacer-2 region. Secondary structures for mycobacterial
      precursor 23S rRNA and for precursor 5S rRNA were devised, based on sequence
      homologies and homologous nucleotide substitutions. All the slow-growers,
      including M. leprae, conform to the same scheme of secondary structure. A
      putative motif for the intrinsic termination of transcription was identified
      approximately 33 bp downstream from the 3'-end of the 5S rRNA gene. The spacer-1
      and spacer-2 sequences may prove a useful supplement to 16S rRNA sequences in
      establishing phylogenetic relationships between very closely related species.

PMID- 7521249
TI  - Unusual in vivo turnover of transfer RNA in Vibrio cholerae.
AB  - Two lines of evidence suggest that, unlike in other organisms, the transfer RNAs
      of Vibrio cholerae undergo rapid turnover in vivo. Firstly, the tRNA content of
      V. cholerae cells treated with rifampicin (an inhibitor of initiation of RNA
      synthesis) decreased rapidly and continuously. Secondly, the newly synthesized
      tRNAs were rapidly degraded even under normal conditions of growth; the average
      half life of tRNA was 11.8 min. The degradation is mediated by an enzyme(s),
      present in V. cholerae cytoplasm, that apparently degrades tRNA completely. Rapid
      turnover is balanced by an enhanced rate of tRNA biogenesis, which was calculated
      to be 2.5 times higher than that in Escherichia coli.

PMID- 7521250
TI  - The topography of tangential inhibitory connections in the postnatally developing
      and mature striate cortex of the cat.
AB  - Clustered intrinsic connections in the striate cortex of kittens originate from
      an unclustered, diffusely organized pattern prevailing during the first postnatal
      week. In order to study the participation of inhibitory neurons in this
      reorganization of the connections, we determined the topography of the inhibitory
      tangenital connections in the striate cortex of cats ranging in age between 7 and
      330 days by combining retrograde transport of fluorescent microspheres with GABA
      immunohistochemistry. After small intracortical injections of tracer, neurons
      containing either microspheres only (non-GABAergic neurons) or GABA-like
      immunoreactivity in addition to microspheres (GABAergic neurons) are labelled at
      various horizontal distances from the injection. At the end of the first
      postnatal week, both GABAergic and non-GABAergic neurons are distributed in the
      horizontal plane in an unclustered fashion. During the second postnatal week, the
      tangential connections rearrange rapidly to form clusters. The tendency of the
      cells to form clusters is much weaker, however, in GABAergic than in non
      GABAergic neurons. In regions > 500 microns distant from the centre of injection
      approximately 90% of the non-GABAergic neurons (range 87.5-92.6%) but only 63%
      (range 57.1-72.3%) of the GABAergic neurons reside within the clusters formed by
      the non-GABAergic neurons. These proportions do not change systematically with
      age. In the regions outside the non-GABAergic clusters, GABAergic neurons appear
      to be evenly distributed and not to aggregate in clusters. From postnatal day 7
      forward GABAergic neurons largely retain their overall distribution and density
      in the horizontal plane. When considering all cortical layers (including the
      superficial white matter) the lateral spread of the GABAergic neurons is more
      restricted than that of the non-GABAergic neurons. Systematic changes in the
      lateral spread of inhibitory connections according to postnatal age were not
      observed. We conclude that, like the non-GABAergic neurons, the GABAergic neurons
      have attained an adult-like topography in the horizontal plane by about the end
      of the second postnatal week. From that time until adulthood they display much
      weaker clustering, a higher relative occurrence of short axon collaterals and a
      more restricted lateral distribution than do the excitatory neurons.

PMID- 7521252
TI  - Phylogenetic analysis of the Coscoroba coscoroba using mitochondrial srRNA gene
      sequences.
AB  - In order to study the phylogenetic relationships among Coscoroba, goose, and swan
      lineages, sequences for the complete mitochondrial small ribosomal RNA (srRNA)
      gene were determined from five waterfowl species. Parsimony and distance analyses
      support the branching of Coscoroba prior to the divergence of geese and swans,
      and maximum likelihood analyses give almost equal support to that pattern and to
      the sister group relationship between Coscoroba and swans. The monophyly of the
      geese was confirmed at a statistically significant level. In sequence comparisons
      among waterfowl, transitions increase linearly with transversions, and so we
      conclude that the lack of complete resolution of Coscoroba's position is not due
      to sequence saturation alone, but also reflects relatively close branching times.

PMID- 7521251
TI  - The NO-cGMP pathway in neonatal rat dorsal horn.
AB  - Incubation of slices of neonatal rat spinal cord with nitric oxide donor
      compounds produced marked elevations in cyclic guanosine 3',5' monophosphate
      (cGMP) levels. The excitatory amino acid receptor agonists N-methyl-D-aspartate
      (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) produced
      smaller increases, which were blocked by the nitric oxide synthase (NOS)
      inhibitor L-NG-nitroarginine (NOArg), indicating that these cGMP responses were
      mediated by nitric oxide. Immunocytochemistry revealed that, in response to NMDA,
      cGMP accumulated in a population of small cells and neuropil in laminae II and
      III of the dorsal horn. This area was also shown, by reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) diaphorase histochemistry, to contain NOS. These
      observations suggest that, in the rat spinal cord, NMDA receptor activation is
      linked to the formation of NO and, hence, of cGMP. This pathway is located
      selectively in the superficial dorsal horn, consistent with a role in the
      processing of nociceptive signals.

PMID- 7521253
TI  - Inhibition by spermine of the induction of nitric oxide synthase in J774.2
      macrophages: requirement of a serum factor.
AB  - Polyamines are endogenous regulators of various cell functions. Nitric oxide (NO)
      is a cytostatic and cytotoxic free radical which is produced by the inducible NO
      synthase (iNOS) in immuno-stimulated macrophages. We tested whether spermine
      modulates the induction of iNOS in J774.2 macrophages. Stimulation of macrophages
      by bacterial lipopolysaccharide (LPS) or gamma-interferon increased the
      accumulation of nitrite in the culture medium. Spermine (10(-6) - 10(-4) M)
      inhibited nitrite production without causing cytotoxicity. This inhibition of NO
      formation by spermine was significantly reduced when it was given 6 h after LPS.
      Spermine did not inhibit nitrite accumulation when foetal calf serum was omitted
      from the tissue culture medium. Thus, spermine is an inhibitor of the induction
      of iNOS, and its inhibitory activity requires the presence of a serum factor.

PMID- 7521255
TI  - The effect of the ETA receptor antagonist, FR 139317, on [125I]-ET-1 binding to
      the atherosclerotic human coronary artery.
AB  - 1. The distribution of [125I]-endothelin (ET-1) binding sites on atherosclerotic
      human epicardial coronary arteries has been studied by in vitro receptor
      autoradiography. 2. [125I]-ET-1 binding was to the tunica media and regions of
      neovascularization. 3. Competition studies were carried out in the presence of ET
      1 and the ETA receptor antagonist, FR 139317. The IC50 values for ET-1 at the
      tunica media and regions of neovascularization were similar (mean +/- s.e.mean of
      n = 4 patients, 2.5 +/- 0.9 nM and 2.9 +/- 0.9 nM, respectively) whereas IC50
      values for FR 139317 at regions of neovascularization (607 +/- 34 nM) were
      significantly higher than those of the tunica media (12.6 +/- 2.4 nM) (P <
      0.0001). 4. These results indicate that ETA receptors are present on the tunica
      media of the diseased human coronary artery whereas a different ET receptor
      subtype exists at regions of neovascularization.

PMID- 7521254
TI  - Interdependence of contractile responses of rat small mesenteric arteries on
      nitric oxide and cyclo-oxygenase and lipoxygenase products of arachidonic acid.
AB  - 1. We have examined the effects of nitric oxide inhibition, indomethacin and the
      dual lipoxygenase/cyclo-oxygenase inhibitor, 3-amino-1-[m-(trifluoromethyl)
      phenyl]-2-pyrazoline (BW755C), on the responses of small mesenteric arteries of
      Wistar rats, with and without endothelium, to noradrenaline, potassium chloride,
      endothelin-1, acetylcholine and sodium nitroprusside. 2. Noradrenaline, potassium
      chloride and endothelin-1 caused concentration-dependent contraction of small
      mesenteric arteries. Indomethacin (14 microM) attenuated the contractile response
      to both noradrenaline and potassium chloride. The inhibitory action of
      indomethacin persisted in vessels treated with CHAPS. 3. Acetylcholine produced
      concentration-dependent relaxation in these vessels. Indomethacin (14 microM) had
      no significant effect on the acetylcholine concentration-response relationship.
      4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) potentiated the
      contractile response to both noradrenaline and potassium chloride and inhibited
      acetylcholine-induced relaxation. Indomethacin attenuated the effects of L-NAME.
      5. BW755C inhibited the contractile response to noradrenaline and potassium
      chloride but not to endothelin-1. The inhibitory effects of BW755C persisted in
      the presence of indomethacin and in vessels treated with CHAPS. 6. BW755C
      enhanced endothelium-dependent relaxation, as assessed by the response to
      acetylcholine. In the presence of indomethacin, BW755C produced a shift to the
      right of the concentration-response curve to acetylcholine. 7. Inhibition of
      nitric oxide synthase with L-NAME, reversed the inhibitory effect of BW755C on
      noradrenaline- and potassium-induced contraction. L-NAME and BW755C in
      combination resulted in a shift to the right of the concentration-response curve
      to acetylcholine. 8. Sodium nitroprusside produced concentration-dependent
      relaxation of the vessels. Endothelium removal reduced the maximum relaxation to
      nitroprusside. BW755C did not alter the response to sodium nitroprusside in
      vessels with or without endothelium.9 .These data support the existence of two
      vasoconstrictor products of arachidonic acid released during contraction of small
      mesenteric arteries with noradrenaline and potassium chloride: a cyclo-oxygenase
      product and a lipoxygenase product both of which appear to be largely endothelium
      independent.

PMID- 7521256
TI  - Induction of nitric oxide synthase in cultured vascular smooth muscle cells: the
      role of cyclic AMP.
AB  - 1. Interleukin-1 beta (IL-1 beta) is a potent stimulant of inducible nitric oxide
      synthase (iNOS) mRNA and nitric oxide (NO) production in vascular smooth muscle
      (VSM) cells in culture. These studies investigate the role of adenosine 3':5'
      cyclic monophosphate (cyclic AMP) in this process. 2. Dibutyryl cyclic AMP (db
      cyclic AMP, 0.1-1 mM), forskolin (1-10 microM) and the phosphodiesterase
      inhibitor, Ro 20-1724 (1-10 microM), all of which increase intracellular cyclic
      AMP, had no effect on NO production when added alone but markedly enhanced NO
      production by IL-1 beta-stimulated VSM cells in a dose-dependent manner.
      Consistent with a cyclic AMP-mediated action, isoprenaline (1-10 microM)
      increased NO production from IL-1 beta-stimulated cells. Dibutyryl cyclic GMP (db
      cyclic GMP) had no effect at concentrations up to 1 mM. 3. Pursuing these
      observations, iNOS protein levels were examined by Western blot analysis and iNOS
      mRNA levels were measured by reverse transcription and amplification of the
      resultant cDNA using the polymerase chain reaction. In addition to enhancing NO
      production, db cyclic AMP increased iNOS protein and mRNA above that produced by
      IL-1 beta alone. 4. These data demonstrate a major effect of cyclic AMP on
      cytokine-induced NOS activity in VSM cells, mediated at least in part by
      regulating synthesis of iNOS, and has implications for the pathogenesis and
      management of septic shock.

PMID- 7521257
TI  - Vasoconstrictor responses after neo-intima formation and endothelial removal in
      the rabbit carotid artery.
AB  - 1. The present study examined the responses of the rabbit carotid artery to five
      vasoconstrictors after neo-intima formation induced by perivascular collar
      treatment and evaluated the role of constitutive and inducible nitric oxide (NO)
      synthase and endothelial cells (ECs). 2. Ring segments of the rabbit carotid
      artery were mounted in organ chambers for isometric tension recording. Neo-intima
      bearing vessels developed less force (Emax) in response to KCl, the thromboxane
      mimetic U-46619 and 5-hydroxytryptamine (5-HT), but not to angiotensin I and II.
      3. The collar-treatment increased the sensitivity to 5-HT, and decreased the
      sensitivity to angiotensin II. The sensitivity to U-46619 and angiotensin I
      remained unchanged. 4. Mechanical removal of ECs and inhibition of NO
      biosynthesis by NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L
      NOARG) increased the sensitivity to 5-HT in sham and collar-treated segments to
      the same extent. The effects of collar-treatment and endothelial removal or
      treatment with inhibitors of NO biosynthesis were additive. Inhibition of NO
      biosynthesis failed to augment sensitivity to 5-HT after endothelial denudation.
      L-NOARG increased the force development to KCl in sham and collar-treated
      segments to the same extent. However, L-NMMA and L-NOARG failed to augment the
      contractile responses of neo-intima-bearing vessels to 5-HT and KCl after
      endothelial removal. 5. The responses to angiotensin I were not altered, either
      by the neo-intima or by endothelial removal. In arteries with a neo-intima the
      sensitivity to angiotensin II was decreased. Removal of the endothelium or
      incubation with L-NOARG counteracted this rightward shift and increased Emax.6.
      Our results demonstrate that contractions to 5-HT, angiotensin II and KCl are
      modulated by NO in both sham and neo-intima-bearing vessels. Inhibition of NO
      biosynthesis and collar treatment resulted in additive effects on the EC50
      values, suggesting that the 5-HT and angiotension (AT) receptors on the smooth
      muscle cells are also modified by the formation of a neo-intima. Furthermore, the
      reduced contractile responses of segments with a neo-intima are not due to NO
      formed by an inducible NO synthase in those vessels.

PMID- 7521258
TI  - Nitrovasodilator-induced relaxation and tolerance development in porcine vena
      cordis magna: dependence on intact endothelium.
AB  - 1. Isolated segments of porcine vena cordis magna exhibited a reproducible
      contractile activity upon application of prostaglandin F2 alpha (PGF2 alpha) or
      KCl, that was independent of the presence of intact endothelium. Substance P (3
      nM) elicited strictly endothelium-dependent relaxations amounting to 46.1 +/-
      1.4% (n = 206) of contractions induced by 10 microM PGF2 alpha. 2. S-nitroso-N
      acetyl-D,L-penicillamine (SNAP), a compound that spontaneously liberates nitric
      oxide, concentration-dependently relaxed PGF2 alpha-precontracted (50 microM)
      venous segments. Tolerance induction (incubation with 100 microM SNAP for 30 min)
      within the same segments resulted in a 3 fold attenuation of this effect, which
      was not further reduced after additional preincubation with glyceryl trinitrate
      (GTN). Removal of endothelium or the presence of N omega-nitro-L-arginine
      methylester (L-NAME) significantly improved the potency of SNAP before and after
      tolerance induction. 3. Concentration-dependent relaxations induced by GTN in non
      tolerant veins were similar in the presence and absence of endothelium but much
      more reduced in tolerant endothelium-denuded (75 fold) compared to intact (20
      fold) segments. In contrast, the presence of L-NAME significantly improved GTN
      activity solely in non-tolerant veins, which, therefore, also resulted in a more
      pronounced attenuation of activity due to tolerance induction (100 fold).
      Preincubation of intact veins with SNAP also reduced GTN-activity but to a lesser
      extent (10 fold). 4. The more delayed but much longer, and compared to GTN
      somewhat weaker, acting new nitrovasodilator N-(3-nitrato-pivaloyl)-1
      cysteineethylester (SPM 3672) was more potent in denuded than intact non-tolerant
      venous segments. Induction of tolerance by GTN resulted in a 2 fold-attenuation
      of potency. This effect was increased to 15 fold in denuded veins but solely due
      to enhanced potency of SPM 3672 caused by removal of endothelium.5. These data
      demonstrate that intact endothelium of porcine vena cordis magna attenuates the
      relaxant potency of nitrovasodilators but also probably participates in vascular
      bioactivation of GTN.We suggest that the reduced potency of nitrovasodilators is
      due to endogenous production of nitricoxide, which may affect the soluble
      guanylate cyclase/cyclic GMP-system or inhibit nitrate bioactivation pathways.

PMID- 7521259
TI  - Effect of topical administration of L-arginine on formalin-induced nociception in
      the mouse: a dual role of peripherally formed NO in pain modulation.
AB  - 1. We investigated the effects of intraplantar (i.pl.) administration of L
      arginine and NG-nitro-L-arginine methyl ester (L-NAME) on formalin-induced
      behavioural nociception in the mouse. 2. L- but not D-arginine, at 0.1-1
      microgram per paw, coadministered with i.pl. formalin, enhanced the second-but
      not the first-phase nociceptive responses, whereas it was without significant
      effects at 3 micrograms per paw, and conversely, produced antinociception at 10
      micrograms per paw, resulting in a bell-shaped dose-response curve. 3. L-NAME at
      0.1-1 microgram per paw, when administered i.pl., exhibited antinociceptive
      activity in the second phase in a dose-dependent manner, although its D
      enantiomer produced no effect. 4. An antinociceptive dose (1 microgram per paw)
      of L-NAME (i.pl.) considerably reduced the increase in second-phase nociception
      elicited by low doses (1 microgram per paw) of i.pl. L-arginine. The second-phase
      nociception decrease induced by a large dose (10 micrograms per paw) of i.pl. L
      arginine was markedly reversed by i.pl. L-NAME at 0.1 micrograms per paw, raising
      it to a level above that of the control (formalin only). 5. These results suggest
      that peripheral NO plays a dual role in nociceptive modulation, depending on the
      tissue level, inducing either nociceptive or antinociceptive responses.

PMID- 7521261
TI  - Sensitivity to protein kinase C inhibitors of nicardipine-insensitive component
      of high K+ contracture in rat and guinea-pig aorta.
AB  - 1. In the rat and guinea-pig aorta, we observed that the contraction to
      hypertonically-added K+, unlike the isotonic K(+)-induced contraction, was only
      partially sensitive to nicardipine (0.1, 1 and 10 microM), an L-type Ca2+ channel
      blocker and occurred in Ca(2+)-free medium containing 50 microM EGTA. We have
      characterized this nicardipine-insensitive hypertonically-added K+ contraction.
      2. The contraction induced by an equi-osmolar concentration of mannitol was
      similar in size to that evoked by hypertonically-added K+. 3. When the tissue was
      depleted of its internal Ca2+ stores with various agents such as phenylephrine
      (10 microM) cyclopiazonic acid (30 microM), thapsigargin (1 microM) or ryanodine
      (30 microM), or by incubation in Ca(2+)-free medium over 30 min, little effect
      was observed on the high K+ contracture in the presence of L-type Ca2+ channel
      blockade. 4. Phentolamine (10 microM) or indomethacin (10 microM) did not reduce
      the contraction induced by high K+. 5. Application of a protein kinase C
      inhibitor, H7 (10, 30 and 100 microM) or calphostin C (1 microM), reduced the
      high K+ contraction but not that caused by an equi-osmolar concentration of
      mannitol. 6. The data suggest that hypertonic K(+)-induced contraction differs
      from that caused by hypertonicity or depolarization per se and invokes membrane
      enzyme activation.

PMID- 7521260
TI  - Evidence for differential roles of nitric oxide (NO) and hyperpolarization in
      endothelium-dependent relaxation of pig isolated coronary artery.
AB  - 1. The possible roles of endothelial and smooth muscle cell hyperpolarization and
      nitric oxide (NO) in endothelium-dependent relaxation were examined in isolated
      rings of pig right coronary artery. 2. The effects of hyperpolarization were
      prevented with high K+ (30-125 mM), isotonic Krebs solutions. Functional
      antagonism due to high K(+)-induced smooth muscle contraction was prevented with
      0.3 microM nifedipine (in all treatments, for consistency). All rings were
      contracted with the thromboxane-mimetic U46619, (1-100 nM) to bring them to an
      initial active force of within 30-50% of maximum contraction. 3. High K+ had no
      effects on the sensitivity (EC50) or time course of endothelium-dependent
      (substance P, SP; bradykinin, BK; calcimycin, A23187) and -independent (sodium
      nitroprusside, SNP) agents. Maximum relaxations (Rmax) to SP, BK and A23187 were
      reduced significantly by approximately 20% but only with 125 mM K+. 4. In normal
      K+ Krebs solution (5.9 mM), NG-nitro-L-arginine (L-NOARG; 100 microM) caused 40%,
      20% and no reduction in Rmax for SP, BK and SNP respectively. EC50s for SP and BK
      were decreased significantly by approximately two fold whereas that for SNP was
      increased significantly by approximately ten fold. At all high K+ concentrations
      (30-125 mM), L-NOARG (100 microM) caused complete inhibition of relaxations to SP
      and BK but those to SNP were unaffected. 5. High K+ (30 mM) unmasked potent and
      concentration-dependent inhibition of relaxations of SP by L-NOARG. At 10 microM
      L-NOARG, all relaxation responses to SP were abolished and at the higher
      concentrations of SP (1-10 nM) small but significant contractions were observed.
      6. N0-monomethyl-L-arginine (L-NMMA) had similar effects on relaxations to SP in
      the presence of 30 mM K+ except that maximum inhibition (40%) of Rmax was
      achieved at 10 MicroM L-NMMA and this was not increased with either 100 or 1000
      MicroM L-NMMA. In normal K+, L-NMMA (1000 MicroM) only decreased the EC50 by
      approximately two fold, without affecting Rmax.7. High choline+ (25, 75 and 125
      mM) isotonic Krebs also had no direct effect on the relaxations to SP,but like
      high K+, enabled L-NOARG (100 MicroM) to inhibit these responses completely.
      Neither charybdotoxin(30 nM) nor substitution of 25 mM NaCl with 50 mM sucrose
      had any direct effect on relaxations to SP or on the block of relaxations to SP
      by L-NOARG (100 MicroM).8. In conclusion, most if not all of the endothelium
      dependent relaxation in the pig coronary artery in vitro is due to NO, but
      hyperpolarization can supplement 60% -80% of this response if NO synthesis is
      blocked. Multiple endothelium-derived factors could not only explain
      heterogeneity of the degree of block of endothelium-dependent relaxation
      responses by L-arginine analogues, but also constitute important 'back-up'
      mechanisms for control of arterial diameter.

PMID- 7521263
TI  - [Effect of chrome compounds and other chemicals in the content of cement and
      clincker dust on metabolic parameters++ of lymphoid organs in rats].
AB  - Effect of seven-day enteral administration of clinkers, cement and dust
      sedimented on electric filters on DNA and RNA, total protein levels, adenylate
      desaminase (AD) and alkaline phosphatase (AP) activities in thymus und spleen was
      shown in rats. Harmful effect of industrial dust on the lymphatic organs was
      maximal in thymus: diminished lymphatic tissue, decreased DNA, RNA and total
      protein levels, increased AD and AP activities. Compounds of chromium with lead,
      copper and mercury appeared to have maximal harmful effect on the lymphatic
      tissue.

PMID- 7521265
TI  - Hypofractionated radiation therapy in the treatment of superior vena cava
      syndrome.
AB  - We retrospectively reviewed 46 patients with superior vena cava syndrome during
      the period 1986-1992. The common symptoms included congestion of collateral veins
      of the neck, anterior chest wall, face, eyelids and right arm. Dyspoea and
      cyanosis occurred less frequently. In all but two patients a histological
      diagnosis was made by invasive and non-invasive examination without
      complications. In 82% of all patients a primary lung carcinoma was the cause of
      the superior vena cava syndrome. For 39 patients radiotherapy was the first
      treatment of choice. To relieve the distressing symptoms patients received one of
      two regimens employing hypofractionated radiotherapy. In regimen 3F, 25 patients
      received three weekly high dose fractions of 8 Gy delivering a total dose of 24
      Gy. Regimen 2F, applied to seven patients, consisted of two weekly fractions of 8
      Gy, giving a total of 24 Gy. In both regimens a good palliative result was
      established, however the results of the 3F regimen were superior. Using the 3F
      regimen a partial response was obtained in 96% of all patients, and 56% achieved
      a complete response. With the 2F regimen a partial response was achieved in 70%
      of all patients, and a complete response in only 28%. Minimal side effects were
      noted. After reviewing our experience, the 3F regimen is recommended for rapid
      and effective relief of the superior vena cava syndrome.

PMID- 7521262
TI  - Nitric oxide-mediated inhibitory response of rat proximal colon: independence
      from changes in membrane potential.
AB  - 1. We studied the relation of nitric oxide-mediated relaxation of smooth muscle
      to changes in membrane potential of cells in the proximal colon of rats. 2. The
      resting membrane potential and electrical field stimulation (EFS)-induced
      junction potentials were recorded from the circular and longitudinal muscle
      cells. 3. Localized distension with a small balloon caused relaxation of the
      circular muscle on the anal side of the distended region (descending relaxation).
      Relaxation of the longitudinal muscle was also induced by EFS. 4. Inhibitory
      junction potentials (i.j.ps) were recorded from all circular muscle cells tested,
      but rarely from the longitudinal muscle cells. 5. The i.j.ps were recorded only
      in the presence of atropine but relaxations of both muscles were induced even in
      the absence of atropine. 6. Apamin (100 nM) completely abolished the i.j.ps
      recorded in both circular and longitudinal muscle cells, but had no significant
      effect on the relaxations of either. 7. In contrast to apamin, Ng nitro-L
      arginine (10 microM) inhibited the relaxations of both muscles, but did not
      affect the i.j.ps. 8. Exogenously added nitric oxide (0.1-10 microM) induced
      relaxations of both muscles concentration-dependently, but did not affect the
      membrane potentials at these concentrations. 9. These data strongly suggest that
      nitric oxide-mediated relaxation of rat proximal colon is not associated with the
      i.j.ps of the cell membrane.

PMID- 7521269
TI  - Analysis of human blood cell development in the SCID-hu mouse, an in vivo replica
      of the human fetal hematopoietic system.
AB  - Human fetal blood tissues implanted in the SCID immuno-deficient mouse are
      tolerated and develop considerably. The bone marrow maintains its autonomous
      hematopoietic function for several months. Conversely, thymic lymphopoiesis can
      continue over the long term only in the presence of an appropriate source of stem
      cells. This in vivo replica of the human blood system can be used to test the
      hematogenic abilities of candidate populations of human hematopoietic stem cells,
      as suggested by the hematogenic reconstitution of human thymus and marrow in SCID
      mice obtained from purified CD34+ precursors. In the same model, hematogenic
      activity of CD34+ cells was limited to the sub-population of these precursors
      coexpressing the antigen Thy-1. These results, combined with those of in vitro
      analyses, suggest that the population of CD34+ Thy-1+ components of fetal liver
      and of the bone marrow is extremely rich in human hematopoietic stem cells.

PMID- 7521266
TI  - Modified Fontan procedure for complex congenital heart disease.
AB  - The Fontan procedure is frequently used for correction of complex congenital
      heart disease, but the postoperative morbidity and mortality rates are still
      high. The results in 35 consecutive patients who underwent the Fontan procedure
      from January 1980 to June 1991 are reviewed. The patients comprised 26 boys and
      nine girls aged from 1.7 to 14.8 (mean 6.8) years. The underlying diseases were
      univentricular heart (19 patients), tricuspid atresia (eight), complete
      atrioventricular canal (three patients, two of whom had straddling
      atrioventricular valve) and other conditions (five). Valved conduits were
      implanted in four patients and non-valved in 15. Direct right atrium-pulmonary
      artery anastomosis was performed in 16 patients. The overall hospital mortality
      rate was 23% (eight patients); in the final year of the review it was 11%. Follow
      up of the survivors ranged from 1 to 120 (mean 25) months. All except two
      patients attained New York Heart Association functional class I or II. Three
      patients underwent reoperation for atrioventricular valve regurgitation and
      conduit stenosis with good results. It is concluded that the Fontan procedure is
      a good palliative operation for complex congenital heart disease.

PMID- 7521264
TI  - Neuroendocrine differentiation as a prognostic factor in non-small cell lung
      cancer.
AB  - The prognostic value of clinical and pathological factors in 97 patients with non
      small cell lung cancer (NSCLC), were analyzed through immunohistochemical
      methods. The impact on response rate and survival of age, Karnofsky performance
      status (PS), sex, NSCLC subtype and grade, extent of disease, objective
      chemotherapy response, LDH values, metastatic sites involved and
      immunohistochemical markers of neuroendocrine differentiation (neuron specific
      enolase (NSE), synaptophysin (Sy 38), chromogranin (Chr A) and Leu-7) were
      analyzed. Median age was 61 years and seven patients were women. Histologically,
      58 had squamous cell carcinoma, 28 adenocarcinoma and 11 large cell
      undifferentiated carcinoma. One patient had Stage II, 35 Stage IIIa, 19 Stage
      IIIb and 42 Stage IV. Six patients achieved complete response, 18 partial
      response, 34 stable disease and 39 progressive disease. NSE was negative in 54.3%
      of cases as was Sy 38 (77.4%), Chr A (97.8%) and Leu-7 (95.8%). We have found
      correlation between neuroendocrine differentiation and absence of P-Glycoprotein
      expression; patients included in this subset had a higher response rate but no
      evidence of longer survival. The univariate analysis showed that four parameters
      had significant adverse effect on survival: non-responders, poor PS, abnormal LDH
      value and absence of NSE expression. Multivariate analysis showed that the best
      combination of independent prognostic factors in predicting survival was: PS and
      NSE expression by immunohistochemical methods.

PMID- 7521270
TI  - Diagnostic and therapeutic applications of angiogenesis research.
AB  - Certain principles of the angiogenic process elucidated in the laboratory over
      the past 3 decades have now been translated to clinical application. These
      applications are in the areas of prognosis, inhibition of angiogenesis, and
      acceleration of angiogenesis. As more experience is gained from these studies we
      may begin to see the development of therapies for many other angiogenic diseases,
      including diabetic retinopathy, rheumatoid arthritis, and psoriasis. It may be
      possible to increase the rate of neovascularization of a myocardial infarction
      and perhaps even to stimulate the growth of coronary collateral vessels. From
      these laboratory and clinical studies it has become clear that angiogenesis is a
      fundamental process that dominates diseases in many different branches of
      medicine and surgery. A clear understanding of the biological and molecular
      aspects of this process will be critical to the successful treatment of a wide
      spectrum of "angiogenic diseases" [53].

PMID- 7521268
TI  - Developmental relationships between hemopoiesis and vasculogenesis.
AB  - Using avian chimeras, we have demonstrated earlier that the stem cells seeding
      the definitive hemopoietic organs form within the embryo rather than in the yolk
      sac. We now report experimental evidence indicating that hemopoietic progenitors
      appear in mouse embryos in the para-aortic splanchnopleura, a location similar to
      the one that produces stem cells in avian embryos. This structure obtained from
      E8.5 embryos was grafted under the kidney capsule of adult SCID mice. One
      compartment of the B lymphoid system became reconstituted with cells derived from
      the graft, that were identified with genetic and antigenic markers. In vitro data
      are also in favor of the production of progenitors from this structure. Finally a
      strategy designed to understand the developmental links between the endothelial
      network and hemopoietic cells is described. It is based on the expression
      patterns of two protooncogenes, c-ets1 and c-myb, activated during the
      amplification period of each of these lineages.

PMID- 7521267
TI  - Tetralogy of Fallot: intracardiac repair in 840 subjects.
AB  - Since 1967, when the first intracardiac repair was performed in this centre,
      until 1991, 840 symptomatic subjects with tetralogy of Fallot have undergone
      corrective surgery. Cardiac catheterization and angiocardiography were carried
      out in all patients. Cardinal findings on the clinical status of these subjects
      are outlined. A substantial number of patients (244; 29.0%) were > 15 years of
      age. Historically, a transannular pericardial gusset has been utilized in 578
      (68.8%), and in 423 (93.0%) during the past decade. The incidence of residual
      interventricular septal defects has been 0.68% and occurrence of complete heart
      block after surgery 0.4%. Death occurred in 86 patients (10.2%) within 30 days of
      operation and later in 40 subjects (4.8%). Long-term results have been excellent
      with good haemodynamic status in > 90% of subjects in the follow-up period.
      Associated features including absent pulmonary valve, absent left pulmonary
      artery, and previous palliative shunts did not alter the outcome; however, a
      raised haematocrit (> 0.65) was associated with an increased mortality rate.

PMID- 7521271
TI  - Xenopus goosecoid: a gene expressed in the prechordal plate that has dorsalizing
      activity.
AB  - gsc is a homeobox gene expressed in the dorsal lip of the blastopore in Xenopus.
      Its mRNA can mimic many aspects of Spemann's organizer activity when
      microinjected into the ventral side of the embryo. In the present study we
      analyze gsc expression in late gastrula and neurula embryos of Xenopus. At these
      stages gsc is expressed in the prechordal plate, an anterior mesodermal structure
      underlying the forebrain. Furthermore, we studied the dorsalizing activity of gsc
      in animal caps and found that UV-sensitive cofactors in the marginal zone are
      required to induce dorso-anterior mesoderm in concert with gsc. FGF, an inducer
      of ventral mesoderm, cannot substitute for these factors.

PMID- 7521272
TI  - Pancreatic cancer.
AB  - Pancreatic cancer is a devastating disease for the patient and presents
      challenging diagnostic and management problems for the physician. A range of
      serologic and radiologic studies are available for evaluation and staging of this
      disease. However, invasive studies, including laparotomy, are often necessary to
      establish the diagnosis and resectability. Despite advances in diagnostic
      technology that have shortened the interval between onset of symptoms and
      definitive treatment, no appreciable impact on survival has been demonstrated
      conclusively. Operative resection offers the only hope for cure, but fewer than
      15 percent of patients have resectable disease at the time of diagnosis.
      Palliative therapy, whether operative or nonoperative, can be performed with low
      morbidity and provides significant relief of symptoms. Combined-modality
      treatment with chemotherapy and radiation therapy prolongs survival following
      curative resection.

PMID- 7521273
TI  - Expression of the estrogen receptor in human thyroid neoplasms.
AB  - The expression and quantitation of the estrogen receptor (ER) in human thyroid
      tumors were examined by biochemical, immunohistochemical, and reverse
      transcriptase-polymerase chain reaction (RT-PCR) techniques. For this study,
      neoplasms, adenomatous goiters and adjacent normal thyroid tissues were obtained
      from 35 patients which included 10 cases of papillary carcinomas, 17 cases of
      adenomas and 8 cases of adenomatous goiters. Regardless of the histopathological
      subtype, ER was detected in 19% (5/27) of the neoplastic tissues with the mean
      value of ER content of 5.0 +/- 1.3 fmol/mg protein and the mean Kd value of 0.38
      +/- 0.28 nM. ER was also detected, but at a lower concentration (2.8 +/- 1.6
      fmol/mg protein), in the surrounding normal tissues. There was no significant
      difference between the neoplasms and adenomatous goiters with respect to the
      incidence of ER positivity and ER content. Furthermore, ER-positive specimens, as
      determined by both biochemical and immunohistochemical techniques, also showed
      the expression of ER mRNA detected by RT-PCR method. These results demonstrate
      that both ER mRNA as well as ER protein are expressed in thyroid neoplasms. This
      suggests the possibility that estrogen may affect the tumorigenesis or the
      progression of some thyroid neoplasms.

PMID- 7521274
TI  - Suppression of nitric oxide production by cyclosporin A and FK506A in rat
      vascular smooth muscle cells.
AB  - 1. The effects of the immunosuppressants cyclosporin A (CsA) and FK506 on nitric
      oxide (NO) synthesis induced by lipopolysaccharide (LPS) or cytokines were
      examined in rat vascular smooth muscle cells (VSMC) in culture. 2. CsA inhibited
      by up to 90% the accumulation of nitrite induced by LPS, but FK506 had a weaker
      effect on nitrite accumulation induced by LPS in these cells. Both CsA and FK506
      (at 1 mumol/L) significantly inhibited nitrite production induced by recombinant
      murine interleukin-1 beta (rIL-1 beta). 3. Given their differing potency, it is
      likely that CsA and FK506 suppress induction of NO synthase through different
      intracellular mechanisms. This action could contribute to the side effects of CsA
      therapy.

PMID- 7521275
TI  - Ionic mechanisms mediating the acetylcholine-elicited contraction in Aplysia
      buccal muscle.
AB  - Ion channel mechanisms mediating acetylcholine (ACh)-elicited contractions in
      Aplysia buccal muscles were investigated using conventional force and membrane
      potential recording techniques and whole-cell voltage clamping of dissociated
      buccal muscle fibers. Previous work on buccal muscles of Aplysia showed that
      acetylcholine (ACh) depolarizes muscle fibers to, at most, -30 mV and that
      contraction is dependent upon extracellular calcium. In intact muscle, removal of
      either calcium or sodium from the extracellular medium reduced ACh-elicited
      depolarization. Absence of each ion reduced the depolarization approximately 50%
      at low [ACh], but at high [ACh], absence of sodium had a greater effect, while
      absence of calcium had a proportionally smaller effect on depolarization.
      Nifedipine (3 microM) reduced contraction by 50% with little accompanying change
      in depolarization. In whole cell voltage-clamping of isolated muscle fibers, ACh
      elicited an inward current at resting potential. The reversal potential for ACh
      elicited current was -24 +/- 6 mV. The current-voltage curve was rectified, with
      a bend in the inward direction near -35 mV. In zero calcium medium, ACh-elicited
      current averaged 54% of control, and in zero sodium medium, 42% of control.
      Nifedipine reduced ACh-elicited current by less than 20%. Amiloride, an inhibitor
      of Aplysia buccal muscle contraction, reduced ACh-elicited current by 30-70%. A
      model based on the above results is that ACh depolarizes muscle fibers by opening
      channels with a reversal potential of about -30 mV that are permeable to calcium,
      sodium, and at least one other ion. Depolarization activates voltage-dependent
      calcium channels, enabling activator calcium to enter the fibers through both ACh
      operated and voltage-dependent channels.

PMID- 7521276
TI  - The influence of ambient salinity and temperature on lipid metabolism in toad
      (Bufo bufo) skin. Is phosphatidylethanolamine an endogenous regulator of ion
      channels?
AB  - Incorporation of (32P) phosphate and (14C) acetate into frog (Rana temporaria)
      skin phospholipids in vitro was positively correlated to skin MR cell density.
      Transport across toad (Bufo bufo) skin and incorporation into skin phospholipids
      of the radioactive tracers were independent of transepithelial electrical
      potential in vitro. While all the incorporations in vitro showed (32P) and (14C)
      frog and toad skin phospholipid patterns dominated by phosphatidylcholine
      independent of adaptational temperature and salinity--corresponding phospholipid
      patterns dominated by phosphatidylethanolamine (PE) were found in vivo, when
      toads adapted to Ringer solution were transferred to tap water containing tracer
      amounts of (32P) phosphate and (14C) acetate. PE could play a role in the
      formation of a "hydrophilic" environment and thereby, e.g. stabilise the integral
      membrane proteins that regulate the function of ion channels.

PMID- 7521277
TI  - A novel angiogenesis model using interstitial cells derived from skeletal muscle.
AB  - A novel angiogenesis model using co-culture of endothelial and interstitial cells
      was developed, in which bovine capillary endothelial cells (BCEC) formed
      capillary-like structure on the monolayer of interstitial cells (like smooth
      muscle cells) isolated from rat skeletal muscle. The capillary formation of BCEC
      occurred even under serum-free conditions. Insulin stimulated the capillary
      growth under serum-free condition, but not BCEC growth in the single culture
      system. These results suggested that the insulin effect on the capillary growth
      was brought about indirectly through the interstitial cells, and that this co
      culture system may be useful for the study of angiogenesis (especially in
      skeletal muscle).

PMID- 7521278
TI  - Palliation of rectosigmoid neoplasms with Nd:YAG laser treatment.
AB  - PURPOSE: The aim of this study was to evaluate the effect of Nd:YAG laser
      treatment as palliation for rectosigmoid neoplasms. METHODS: Indications for
      laser therapy, the degree and duration of symptom relief, complication rate, and
      survival time were recorded in consecutive patients. RESULTS: Seventy-four
      patients entered the study. Poor general health in older patients, and
      disseminated or complicating disease were the most frequent indications for
      therapy. Fifty-five (74 percent) patients experienced good symptomatic effect
      from the treatment. Six complications occurred: five cases of perforation and one
      case of moderate bleeding. There was no mortality. The median survival was seven
      months (range, 14 days-39 months). CONCLUSION: Laser treatment is a good
      palliative method in patients with colorectal cancer, especially in patients with
      local recurrence or symptoms from non-resected tumors.

PMID- 7521279
TI  - Tumor angiogenesis and rectal carcinoma.
AB  - PURPOSE: This study was designed to determine whether those rectal cancers that
      demonstrated increased vessel ingrowth or angiogenesis behave in a different
      fashion. METHODS: The paraffin blocks of 48 rectal cancers removed by low
      anterior or abdominoperineal resection were recalled and immunostained with a
      monoclonal antibody specific for endothelial cell Factor VIII. The intense
      reddish brown color imparted to blood vessels facilitated their quantification
      which was undertaken at x100 and x200 magnification. Vessel counts within three
      microscopic fields were averaged and the relationships between angiogenesis score
      and tumor size, depth of invasion, incidence of lymph node or distant metastases,
      and survival were assessed. RESULTS: Significantly higher angiogenesis scores
      were seen in tumors with transmural penetration (at x100, P = 0.002; at x200, P =
      0.002) and in patients dying before five years (at x100, P = 0.013; at x200, P =
      0.034). Although higher angiogenesis scores were seen in patients with larger
      tumors and metastases, these trends were not statistically significant.
      CONCLUSIONS: Our results suggest that the growth of rectal cancer is dependent on
      the ingrowth of new blood vessels, and that increased vascularity promotes
      dissemination and adversely affects survival.

PMID- 7521280
TI  - Segmental migration of the hindbrain neural crest does not arise from its
      segmental generation.
AB  - The proposed pathways of chick cranial neural crest migration and their
      relationship to the rhombomeres of the hindbrain have been somewhat
      controversial, with differing results emerging from grafting and DiI-labelling
      analyses. To resolve this discrepancy, we have examined cranial neural crest
      migratory pathways using the combination of neurofilament immunocytochemistry,
      which recognizes early hindbrain neural crest cells, and labelling with the vital
      dye, DiI. Neurofilament-positive cells with the appearance of premigratory and
      early-migrating neural crest cells were noted at all axial levels of the
      hindbrain. At slightly later stages, neural crest cell migration in this region
      appeared segmented, with no neural crest cells obvious in the mesenchyme lateral
      to rhombomere 3 (r3) and between the neural tube and the otic vesicle lateral to
      r5. Focal injections of DiI at the levels of r3 and r5 demonstrated that both of
      these rhombomeres generated neural crest cells. The segmental distribution of
      neural crest cells resulted from the DiI-labelled cells that originated in r3 and
      r5 deviating rostrally or caudally and failing to enter the adjacent preotic
      mesoderm or otic vesicle region. The observation that neural crest cells
      originating from r3 and r5 avoided specific neighboring domains raises the
      intriguing possibility that, as in the trunk, extrinsic factors play a major role
      in the axial patterning of the cranial neural crest and the neural crest-derived
      peripheral nervous system.

PMID- 7521282
TI  - The role of E-cadherin and integrins in mesoderm differentiation and migration at
      the mammalian primitive streak.
AB  - We have examined the role of cell-cell and cell-extracellular matrix (ECM)
      interactions during mesoderm differentiation and migration at the primitive
      streak of the mouse embryo with the use of function-perturbing antibodies.
      Explants of epiblast or mesoderm tissue dissected from the primitive streak of
      7.5- to 7.8-day mouse embryos were cultured on a fibronectin substratum in serum
      free, chemically defined medium. After 16-24 hours in culture, cells in explants
      of epiblast exhibited the typical close-packed morphology of epithelia, and the
      tissue remained as a coherent patch of cells that were shown to express
      transcripts of the cytokeratin Endo B by in situ analysis. In contrast, cells in
      explants of primitive streak mesoderm exhibited a greatly flattened, fibroblastic
      morphology, did not express Endo B transcripts, and migrated away from the center
      of the explant. As epiblast cells in vivo undergo the epithelial-mesenchymal
      transition at the primitive streak, they cease expressing the prominent calcium
      sensitive cell adhesion molecule E-cadherin (uvomorulin, Cell-CAM 120/80). We
      asked whether the loss of E-cadherin expression was a passive result of
      differentiation or if it might play a more causative role in mesoderm
      differentiation and migration. Culture with function-perturbing antibodies
      against E-cadherin caused cells within epiblast explants to lose cell-cell
      contacts, to flatten, and to assume a mesenchymal morphology; they were also
      induced to migrate. Anti-E-cadherin antibodies had no effect on explants of
      primitive streak mesoderm. In immunofluorescence studies, anti-E-cadherin-treated
      epiblast cells ceased to express SSEA-1, a carbohydrate moiety that is lost as
      mesoderm differentiates from the epiblast in vivo, and they also ceased to
      express E-cadherin itself. In contrast, these cells began to express the
      intermediate filament protein vimentin, a cytoskeletal protein characteristic of
      the primitive streak mesoderm at this stage of development. As epiblast cells
      differentiate into mesoderm, their predominant adhesive interactions change from
      cell-cell to cell-substratum. Therefore, we also investigated the adhesive
      interactions between primitive streak tissues and extracellular matrix (ECM)
      components. Epiblast explants adhered well to fibronectin, more poorly to laminin
      and type IV collagen, and not at all to vitronectin. In contrast, mesoderm
      explants attached well to all these proteins. Furthermore, epiblast, but not
      mesoderm, displayed an anchorage-dependent viability in culture. After anti-E
      cadherin treatment, epiblast cells that had assumed the mesenchymal morphology
      did attach to vitronectin, another characteristic shared with primitive streak
      mesoderm.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7521283
TI  - Unusual laryngeal hyperkeratosis.

PMID- 7521281
TI  - W-sash affects positive and negative elements controlling c-kit expression:
      ectopic c-kit expression at sites of kit-ligand expression affects melanogenesis.
AB  - The receptor tyrosine kinase c-kit and its cognate ligand KL are encoded at the
      white spotting (W) and steel (Sl) loci of the mouse, respectively. Mutations at
      both the W and the Sl locus cause deficiencies in gametogenesis, melanogenesis
      and hematopoiesis (erythrocytes and mast cells). The W-sash mutation differs from
      most W mutations in that it affects primarily mast cells and melanogenesis but
      not other cellular targets of W and Sl mutations. Thus, Wsh/Wsh mice are fertile
      and not anemic, but they lack mast cells in their skin and intestine and are
      devoid of coat pigment. Heterozygotes are black with a broad white sash/belt in
      the lumbar region. In order to determine the basis for the phenotypes of W-sash
      mice, we investigated c-kit RNA and protein expression patterns in adult Wsh/Wsh
      mice and during embryonic development. We show that c-kit expression is absent in
      bone-marrow-derived Wsh/Wsh mast cells, the fetal and the adult lung, and the
      digestive tract at embryonic day 13 1/2 (E13 1/2), tissues that normally express
      c-kit. Unexpectedly, in E10 1/2 and 11 1/2d Wsh/Wsh embryos, we found c-kit
      expression in the dermatome of the somites, the mesenchyme around the otic
      vesicle and the floorplate of the neural tube, structures known to express the c
      kit ligand in wild-type embryos. The ectopic c-kit expression in Wsh homozygous
      embryos does not affect c-kit ligand expression. The presumed Wsh/Wsh
      melanoblasts appeared to be normal and, at E10 1/2, similar numbers were found in
      normal and homozygous mutant embryos. At E13 1/2 +/+ embryos had a graded
      distribution of melanoblasts from cranial to caudal with a minimum in the lumbar
      region. Whereas E13 1/2 homozygous Wsh/Wsh embryos essentially lacked c-kit
      positive cells in the skin, E13 1/2 heterozygous Wsh/+ embryos had reduced
      numbers of melanoblasts compared to +/+ with few or none in the lumbar region
      (future sash). It is proposed that ectopic c-kit expression in the somitic
      dermatome affects early melanogenesis in a dominant fashion. Molecular analysis
      of Wsh chromosomal DNA revealed a deletion or rearrangement in the vicinity of
      the c-kit gene. These results provide an explanation for the Wsh phenotype and
      have implications for the control of c-kit expression.

PMID- 7521284
TI  - Quantitative analysis of the compound muscle action potential in early acute
      inflammatory demyelinating polyneuropathy.
AB  - We quantitated the size and configuration of compound muscle action potentials
      (CMAPs) in 266 nerves (66 median, 67 ulnar, 71 tibial and 62 peroneal) of 72
      patients with acute inflammatory demyelinating polyneuropathy (AIDP) initially
      studied within 19 days of symptom onset. Results were compared with criteria for
      CMAP abnormalities, including criteria for abnormal negative peak duration and
      desynchronisation, derived from a control population of 50 median, ulnar, tibial
      and peroneal nerves. Other motor conduction abnormalities including minimal F
      response latency were also examined. We also analysed patterns of CMAP
      abnormality, peak disability and outcome for AIDP patients who had at least 3
      motor nerves evaluated at first electrophysiologic study. Amongst AIDP nerves,
      low amplitude of the distal CMAP, usually with prolonged distal latency, was much
      more common than an abnormal fall in CMAP amplitude between stimulus sites. Using
      our CMAP criteria more than half of these low amplitude distal responses showed
      prolonged negative peak duration of desynchronisation or both, consistent with
      demyelination. Of the 47 AIDP patients who had 3 or more nerves initially
      studied, 37 (78.7%) had at least 1 motor nerve with a distal CMAP showing
      evidence of temporal dispersion. In addition, those with at least 75% of motor
      nerves showing a pattern of low amplitude of the distal CMAP without a further
      significant fall in amplitude between stimulus sites had greater peak disability
      and a poorer outcome. Assessment of temporal dispersion of the distal CMAP should
      be included in electrophysiologic criteria for acute demyelination. In addition,
      for some patients with AIDP patterns of CMAP amplitude abnormality amongst motor
      nerves are present early in the illness and may provide prognostic information.

PMID- 7521285
TI  - Quantitative studies of F responses in Guillain-Barre syndrome and chronic
      inflammatory demyelinating polyneuropathy.
AB  - We examined F wave mean and minimum latency, mean and maximum amplitude,
      duration, persistence and chronodispersion in 241 nerves from 78 patients with
      Guillain-Barre syndrome (GBS) and 162 nerves from 43 patients with chronic
      inflammatory demyelinating polyneuropathy (CIDP). Results were compared with
      normal criteria derived from 72 median, 73 ulnar and 73 tibial control nerves, to
      determine the relative diagnostic sensitivity of the various F wave parameters. F
      wave abnormalities were found in 92% and 95% of nerves of patients with GBS and
      CIDP respectively. Absence of F responses or prolongation of minimum and mean
      latency were the most frequent abnormalities in both groups. Forty-five (11.2%)
      nerves overall had absent F responses with normal compound muscle action
      potential (CMAP) amplitudes and no significant fall between stimulus sites,
      consistent with isolated proximal conduction block. Forty-four nerves (23.7% of
      nerves in which F waves were present) fulfilled minimum F latency criteria for
      acquired demyelination . Eighty-one (20.1%) nerves had normal conventional motor
      nerve conduction studies and abnormal F responses, not all of which were
      identified by assessing only F absence or minimum latency. Severity of F wave
      abnormalities did not correlate with clinical outcome. Our findings confirm the
      high frequency of proximal nerve lesions in early GBS and CIDP, not all of which
      are associated with distal motor conduction abnormalities, and suggest that
      assessment of multiple F wave parameters, in particular chronodispersion, mean
      latency and mean amplitude (in addition to absence and minimum latency),
      increases the yield of F wave studies.

PMID- 7521286
TI  - Short-latency neck muscle responses to vertical body tilt in normal subjects and
      in patients with spasmodic torticollis.
AB  - EMG responses in the sternocleidomastoid (SCM) and dorsal neck muscles (DNM) to
      vertical head acceleration were studied in normal subjects and in patients with
      spasmodic torticollis, standing on a platform that could be tilted upwards. The
      vertical body displacement and the induced changes in the head-neck angle (a
      flexion-extension sequence) were recorded. Excitatory responses, symmetrical on
      the two sides, were elicited in normal subjects in both muscle groups, at a
      latency of about 60 msec (DNM) and 90 msec (SCM). With the head initially
      extended, the latency of DNM response increased, leaving that of SCM unchanged.
      During an isometric rotatory effort, an early inhibitory period was recorded in
      the active muscles at a latency of about 40 msec. Downward tilt did not evoke the
      responses. The DNM excitatory responses appeared to be related to muscle stretch,
      while those in SCM, as well as the inhibitory responses in both muscles, were
      thought to originate in the vestibular receptors. During active head rotation the
      response increased in amplitude in the active SCM and decreased in the lengthened
      antagonist; decreased responses in the lengthened muscle persisted during passive
      head rotation. This was attributed to an influence from the tonic neck receptors.
      In the patients, SCM responses had normal latency, but were reduced in amplitude
      or absent in the dystonic muscle, in spite of tilt-induced head movements
      comparable to those recorded in normals. The diminution was even bigger if
      compared to normal subjects with the head actively rotated to a similar extent.
      It persisted when the head was returned to normal position by the "geste
      antagoniste." The inhibitory responses were unaffected in the active normal and
      dystonic muscles. The possible role of a deficit of the central vestibular
      connections in the decreased excitatory SCM response in dystonic patients is
      considered.

PMID- 7521287
TI  - H reflexes as a measure for uremic polyneuropathy. A longitudinal study in
      patients treated with dialysis or renal transplantation.
AB  - Assessment of peripheral nerve function in end stage uremia by clinical and
      conventional nerve conduction velocity studies was compared to that using H
      reflex measurements. The latter proved to be the most sensitive technique. The
      results of the test correlated well with clinical and with other neuro
      physiological measures. Nerve function as evaluated by H reflexes remained stable
      during the first 2 years of dialysis, but deteriorated later on. H reflex
      latencies shortened after renal transplantation. The results of H reflex
      measurements did not correlate with biochemical parameters, which makes the test
      a less attractive overall measure for the efficiency of therapy in uremia. In the
      follow-up of patients under treatment for uremic polyneuropathy, however,
      recording of H reflexes provides an important measure.

PMID- 7521288
TI  - H reflex studies in neurolathyrism.
AB  - Sixteen patients with lathyrism, age ranging between 18 and 55 years and duration
      of illness between 2 and 25 years, underwent H reflex studies with the aim of
      studying motor neurone excitability. The patients had marked spasticity (Ashworth
      score ranging between 2 and 5) and mild to moderate leg weakness. Knee and ankle
      reflexes were exaggerated in all and the plantar response was extensor in 14
      patients. The H reflex abnormalities included increased HM ratio indicating
      increased motoneurone excitability, significant lack of vibratory inhibition
      indicating altered transmission in the premotoneuronal portion of the H reflex
      pathway, and lack of reciprocal inhibition (P < 0.01). These H reflex
      abnormalities were not related to spasticity, weakness, clonus or plantar
      response. The H reflex recovery curve in 6 patients revealed increased
      excitability throughout the recovery curve. The secondary facilitation started
      and peaked slightly earlier than normal, and the late depression was not marked
      indicating change in excitability of motoneurones or of interneurones.

PMID- 7521290
TI  - Comparison of two techniques to measure the motor nerve refractory period
      distribution.
AB  - The techniques introduced by Ingram et al. and by Kimura to assess the motor
      nerve refractory period distribution were compared in the peroneal nerve of 28
      healthy subjects. Twenty of these subjects were examined twice with an interval
      of 6-20 days. Results obtained with Ingram's technique yielded a narrower
      refractory period distribution, displayed less inter-individual variability, and
      were more reproducible than those obtained with Kimura's technique. The mean
      refractory period for the 5% slowest recovering fibres (MRP95) was 1.51 msec
      (S.D. 0.14) for Ingram's technique and 2.15 msec (S.D. 0.72) for Kimura's
      technique. The coefficient of variation of the MRP95 was 8% for Ingram's
      technique, and 22% for Kimura's technique. The present data do not allow a
      definite conclusion concerning the association of refractory period with age,
      gender and height. Ingram's technique would be favoured for practical application
      over Kimura's technique on the basis of this study.

PMID- 7521289
TI  - The limits of equilibrium in young and elderly normal subjects and in
      parkinsonians.
AB  - Body sway was studied at various body inclinations, voluntarily maintained for
      about 1 min, in young and elderly normals and in idiopathic parkinsonians. They
      stood on a dynamometric platform, whose output gave the instantaneous centre of
      foot pressure (CFP), its mean value and body sway area, with eyes open (EO) or
      closed (EC). Subjects held the normal upright stance, or the maximum possible
      inclined posture (body straight, rotated at the ankle joints) in forward or
      backward direction, or intermediate postures. EMG was recorded from tibialis
      anterior (TA), soleus (Sol), extensor digitorum brevis (EDB) and flexor digitorum
      brevis (FDB). The cross-correlation function between the profile of the EMG
      envelope and the profile of the shift of CFP along the sagittal plane was
      calculated. In young subjects standing with EO, the maximum extent of antero
      posterior (A-P) displacement of CFP was about 60% of foot length. EC reduced this
      value to about 50%. In the elderly normals, the maximum A-P displacement was
      about 40% (EO) and 30% (EC). In both groups, sway area was minimal during normal
      stance with EO and increased progressively when the subjects leant forward or
      backward. With EC, sway area further increased during normal stance and the rate
      of increase in relation to inclination augmented markedly. Sol was tonically
      active during normal stance. Forward leaning increased Sol EMG and induced
      activity in FDB. TA and EDB were active during backward leaning. The peak of the
      cross-correlation function between Sol EMG and instantaneous CFP was higher
      during normal stance than forward inclination, while the reverse was true for
      FDB. This suggests a role of FDB in the fine-tuning of postural adjustment during
      forward leaning, and a weight-supporting role of Sol. During backward
      inclination, TA but not EDB was cross-correlated with CFP. In the parkinsonians,
      maximum A-P displacement of CFP was just about 30% of foot length (EO; about 20%
      with EC); its extent was inversely correlated with the severity of the disease.
      The relationship between sway area and A-P displacement was similar to the
      elderly, both with EO and EC, within the common range of inclination. In the
      patients affected by the long-term syndrome, A-P displacement was further reduced
      while sway area increase at the critical postures was often absent. In all
      patients, the relationship between muscle activity and body inclination was
      comparable to normal.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7521291
TI  - Motor nerve refractory period distribution assessed by two techniques in diabetic
      polyneuropathy.
AB  - The techniques introduced by Kimura and Ingram et al. were applied to assess the
      distribution of motor refractory periods (DMRPs) in peroneal nerve fibres of 28
      diabetics with symptoms indicating polyneuropathy and in 28 controls. Results
      were compared with conventional motor nerve conduction velocity (MNCV) and
      compound muscle action potential (CMAP) measurements. MRP95 and MRP90 (the 5% and
      10% slowest recovering fibres) obtained with Ingram's technique were prolonged in
      the diabetic patients. In the 26 patients with a value of MRP95 and MNCV, a
      prolonged MRP95 and a decreased MNCV were found in 12 patients. Thus conventional
      MNCV had a sensitivity of 46% to detect neuropathy; addition of MRP95 obtained
      with Ingram's technique raised the sensitivity to 73%. Specificity was 100% in
      both cases. With Kimura's technique or with the fast recovering fibres in
      Ingram's technique, it was not possible to discriminate the patients from the
      controls. This study indicates that measurement of the DMRP with the technique
      introduced by Ingram et al. improves the electrophysiological diagnosis of
      diabetic polyneuropathy.

PMID- 7521292
TI  - Pattern of motor evoked response to repetitive transcranial magnetic stimulation.
AB  - The changes in motor pathway excitability, induced by pairs or trains of
      transcranial magnetic stimuli, were studied. The motor evoked potential (MEP)
      pattern depended on the interstimulus interval (ISI), the stimulus intensity and
      the type of coil employed. At low intensity, using either an 8-shaped or a
      circular coil, there was a test MEP inhibition at ISIs of 50-150 msec. During
      trains of stimuli, this inhibition showed a periodic trend with an interval of
      250-300 msec. At high stimulus intensity we observed a progressive disappearance
      of test MEP inhibition which was incomplete with an 8-shaped coil and complete,
      reaching an MEP facilitation, with a circular coil. The inhibition observed at
      low intensity might be due to cortical inhibitory mechanisms. The effect found at
      high intensity and with the circular coil could depend on the activation of
      deeper and at higher threshold cortico-spinal structures. This hypothesis,
      however, does not explain the simultaneous delay of the test MEP latency which
      might depend on the activation of different cortico-spinal pathways.

PMID- 7521293
TI  - Cervical magnetic stimulation in children and adolescents: normal values and
      evaluation of the proximal lesion of the peripheral motor nerve in cases with
      polyradiculoneuropathy.
AB  - Cervical magnetic stimulation was used to establish the normal values of the
      peripheral motor nerve conduction of the upper extremity muscle in normal
      children and adolescents. Seven patients with peripheral neuropathy were also
      examined to evaluate a lesion in the proximal site of the peripheral motor nerve.
      In normal subjects, onset latencies and negative wave durations tended to
      increase with age. The developmental profile of the latency, corrected for arm
      length, revealed a significant decline until the age of about 5 years. In 4 cases
      with polyradiculoneuropathy, motor evoked potentials following cervical magnetic
      stimulation showed increased latencies, prolonged durations and polyphasic
      shapes. The time differences between latencies by magnetic stimulation and
      peripheral motor conduction times by F technique were significantly prolonged.
      Motor evoked potentials obtained in 3 cases of axonal degeneration, on the other
      hand, showed slightly increased latencies and normal durations. The time
      differences between latencies and peripheral motor conduction times were within
      the normal range. Thus, we consider that cervical magnetic stimulation is a
      useful method for study of peripheral motor conduction in children and
      adolescents, and in particular to evaluate the proximal lesion of the nerve in
      patients with polyradiculoneuropathy.

PMID- 7521294
TI  - Palliation of malignant oesophageal obstruction by endoscopic alcohol injection.
AB  - Thirty six-patients with inoperable cancers of the oesophagus or gastric tumour
      in the cardia were treated by endoscopic alcohol injection. After dilatation
      using Savary dilators, absolute alcohol was injected in 0.5-1 ml aliquots into
      protuberant parts using a sclerotherapy needle. The mean volume per session was
      7.8 ml. The mean dysphagia score improved from 2.7 before treatment to 1.4 after
      treatment (p < 0.001). Complications included mediastinitis in one patient and
      tracheo-oesophageal fistulas in two patients. The mean duration of palliation
      before the development of recurrent dysphagia was 35 days. The mean survival was
      82 days. Endoscopic alcohol injection is effective in relieving malignant
      dysphagia. This inexpensive and easily available technique merits comparative
      studies with more established forms of therapy, such as laser photocoagulation.

PMID- 7521295
TI  - The use of ethanol injection under endoscopic control to palliate dysphagia
      caused by esophagogastric cancer.
AB  - Nine patients with dysphagia caused by unresectable tumors of the esophagus and
      cardia (eight with squamous-cell carcinomas and one with adenocarcinoma) were
      treated with absolute (95 g/l) alcohol mixed with 0.5% methylene blue. Total
      volumes ranging from 16 to 41 ml were injected endoscopically during sessions
      separated at 5-day intervals. The results were evaluated by endoscopic and
      radiological follow-up, as well as clinically, according to Bown's dysphagia
      score. Treatment had to be stopped in one patient with a preexisting
      esophagobronchial fistula. In the remaining eight patients, the mean dysphagia
      score decreased from 3.4 before treatment to 1.2 after treatment. After
      treatment, all patients were able to swallow a solid or semisolid diet. Treatment
      was repeated when dysphagia recurred, with a mean interval of 31.5 days between
      treatments. No complications were encountered. In our view, the preliminary
      results using this simple and inexpensive technique warrant comparative trials
      with other methods of palliation.

PMID- 7521296
TI  - Phylogenetic comparative chemical footprint analysis of the interaction between
      ribonuclease P RNA and tRNA.
AB  - Ribonuclease P RNA is the catalytic moiety of the ribonucleoprotein enzyme that
      endonucleolytically cleaves precursor sequences from the 5' ends of pre-tRNAs.
      The bacterial RNase P RNA-tRNA complex was examined with a footprinting approach,
      utilizing chemical modification to determine RNase P RNA nucleotides that
      potentially contact tRNA. RNase P RNA was modified with dimethylsulfate or
      kethoxal in the presence or absence of tRNA, and sites of modification were
      detected by primer extension. Comparison of the results reveals RNase P bases
      that are protected from modification upon binding tRNA. Analyses were carried out
      with RNase P RNAs from three different bacteria: Escherichia coli, Chromatium
      vinosum and Bacillus subtilis. Discrete bases of these RNAs that lie within
      conserved, homologous portions of the secondary structures are similarly
      protected. One protection among all three RNAs was attributed to the precursor
      segment of pre-tRNA. Experiments using pre-tRNAs containing precursor segments of
      variable length demonstrate that a precursor segment of only 2-4 nucleotides is
      sufficient to confer this protection. Deletion of the 3'-terminal CCA sequence of
      tRNA correlates with loss of protection of a particular loop in the RNase P RNA
      secondary structure. Analysis of mutant tRNAs containing sequential 3'-terminal
      deletions suggests a relative orientation of the bound tRNA CCA to that loop.

PMID- 7521299
TI  - Structural studies of the O-antigenic polysaccharides of Escherichia coli O3 and
      the enteroaggregative Escherichia coli strain 17-2.
AB  - The polysaccharide part of the lipopolysaccharide isolated from an
      enteroaggregative Escherichia coli isolated from a young child with diarrhoea in
      Santiago, Chile (strain 17-2), has been investigated. Sugar and methylation
      analyses of native and partially degraded polysaccharide together with 1H-NMR and
      13C-NMR spectroscopies revealed that the polysaccharide is composed of
      pentasaccharide repeating units. The structure of the repeating unit of E. coli
      strain 17-2 O-polysaccharide is: [formula: see text] The structure of the O
      polysaccharide from E. coli O3 was shown to be identical to that of E. coli
      strain 17-2 by sugar and methylation analyses and by 1H-NMR and 13C-NMR
      spectroscopies.

PMID- 7521298
TI  - Binding of the Grb2 SH2 domain to phosphotyrosine motifs does not change the
      affinity of its SH3 domains for Sos proline-rich motifs.
AB  - Phosphotyrosine peptide binding to Grb2 induces tryptophan fluorescence changes
      in the Src homology 2 (SH2) domain. Affinities are in the nanomolar range, the
      Shc peptide having the highest affinity, followed by peptides mimicking Grb2
      binding sites on EGF and HGF receptors, the putative sites on insulin and IGF-1
      receptors having much lower affinities. Proline-rich peptide binding to the SH3
      domains induces fluorescence changes mainly in the C-terminal SH3. Affinities are
      in the micromolar range, the highest affinity peptides mimicking the first
      proline-rich motif of the Sos C-terminus. Additional residues before this
      PVPPPVPP motif provide a minor contribution to the binding, but the two residues
      after this motif are important and may contribute to specificity. The affinity of
      each SH3 for each proline-rich motif is too low to account for the high stability
      of the Grb2-Sos complex, suggesting that Grb2 recognizes other structural
      features in the Sos C-terminus. Binding of a phosphotyrosine peptide to the SH2
      has no effect on the SH3s. Thus the binding of Grb2 to a receptor or to an
      associated protein phosphorylated on tyrosines is unlikely to activate the
      exchange factor activity of Sos through a conformational change transmitted from
      the SH2 to the SH3 domains.

PMID- 7521300
TI  - A specific association between the glyoxylic-acid-cycle enzymes isocitrate lyase
      and malate synthase.
AB  - There is accumulating evidence that metabolic pathways are organized in vivo as
      multienzyme clusters or metabolons. To assess interactions between consecutive
      enzymes of a pathway in vitro, it is usually essential to modify the physical
      properties of water around the enzymes, e.g. by immobilizing the latter onto a
      solid support. Such immobilized enzyme preparations can be embedded in agarose
      gels and used for affinity electrophoresis [Beeckmans, S., Van Driessche, E. &
      Kanarek, L. (1989) Eur. J. Biochem. 183, 449-454; Beeckmans, S., Van Driessche,
      E. & Kanarek, L. (1990) J. Cell. Biochem. 43, 297-306]. In this study we use the
      aforementioned technique to investigate the association between two plant
      glyoxylic acid cycle enzymes, i.e. isocitrate lyase and malate synthase. A
      specific histochemical staining technique is described for both enzymes. Affinity
      electrophoresis using either isocitrate lyase or malate synthase as the
      immobilized enzyme clearly shows that associations are formed between both
      enzymes. Moreover, experiments with metabolically unrelated enzymes prove that
      the observed interaction is specific.

PMID- 7521297
TI  - Use of photoaffinity crosslinking and molecular modeling to analyze the global
      architecture of ribonuclease P RNA.
AB  - Bacterial ribonuclease P (RNase P), an endonuclease involved in tRNA maturation,
      is a ribonucleoprotein containing a catalytic RNA. The secondary structure of
      this ribozyme is well established, but comparatively little is understood about
      its 3-D structure. In this analysis, orientation and distance constraints between
      elements within the Escherichia coli RNase P RNA-pre-tRNA complex were determined
      by intra- and intermolecular crosslinking experiments. A molecular mechanics
      based RNA structure refinement protocol was used to incorporate the distance
      constraints indicated by crosslinking, along with the known secondary structure
      of RNase P RNA and the tertiary structure of tRNA, into molecular models. Seven
      different structures that satisfy the constraints equally well were generated and
      compared by superposition to estimate helix positions and orientations. Manual
      refinement within the range of conformations indicated by the molecular mechanics
      analysis was used to derive a model of RNase P RNA with bound substrate pre-tRNA
      that is consistent with the crosslinking results and the available phylogenetic
      comparisons.

PMID- 7521301
TI  - Accumulation of reactive oxygen species and oxidation of cytokinin in germinating
      soybean seeds.
AB  - Seed germination is an important developmental switch when quiescent seed cells
      initiate oxidative phosphorylation for further development and differentiation.
      During early imbibition of soybean seeds (Glycine max L. cv. Weber), a superoxide
      dismutase (SOD) activity peak was observed, in embryonic axes, after 6 h
      imbibition. Peroxidase activities, including catalase, were significantly
      increased after 12 h inhibition and during germination phase III. Catalase was
      the most efficient enzyme in catabolizing H2O2 in embryonic axes. When stored at
      42 degrees C and 100% relative humidity, seeds were stressed and lost their
      viability in a time-dependent manner. A significant increase in the Cu, Zn
      superoxide-dismutase activity, and to a lesser extent, Mn superoxide dismutase
      activity was observed during germination in low-viability (stressed) seeds as
      compared to high-viability (unstressed) seeds. Northern blot analysis confirmed
      that superoxide dismutase induction resulted from an accumulation of its
      transcripts in response to the production of O2-. The induction of catalase did
      not occur in low-viability seeds, resulting in dramatic accumulation of H2O2.
      Using capillary electrophoresis, HPLC and NMR we found that the endogenous
      cytokinin, zeatin riboside, was present in large quantities in the high-viability
      seeds, but it was oxidized into adenine in the low-viability seeds. In vitro
      superoxide anion could also oxidize the cytokinin. Zeatin riboside, but not
      adenine, was found to act as a scavenger of superoxide anions and may help to
      maintain seed viability by detoxifying reactive oxygen species. Germination of
      stressed seeds was partially restored by the addition of exogenous cytokinin
      (zeatin riboside). Protection against oxidative stress by cytokinin seemed to be
      a general phenomenon, as Escherichia coli cells were also protected against
      superoxide stress in the presence of cytokinin.

PMID- 7521302
TI  - Age-related vulnerability of developing cholinergic basal forebrain neurons
      following excitotoxic lesions of the hippocampus.
AB  - Previous studies have demonstrated that depleting the hippocampus of endogenous
      neurotrophins via excitotoxic lesions fails to alter the viability of adult
      cholinergic septal/diagonal band neurons. Since cholinergic basal forebrain
      neurons may be more vulnerable during development, we investigated whether
      excitotoxic lesions produced in neonatal animals alter the viability of these
      cells. Postnatal Day 7, 10, 14, and 28 rats pups received unilateral
      intrahippocampal injections of ibotenic acid and were sacrificed 4 weeks later.
      At 7, 10, and 14 days of age, significant reductions in the number of choline
      acetyltransferase (ChAT)- and p75 nerve growth factor receptor (NGFr)
      immunoreactive neurons were observed within the medial septum ipsilateral to the
      hippocampal lesion. In contrast, rats receiving similar lesions on Day 28 failed
      to display a significant reduction in ChAT-immunoreactive medial septal neurons.
      The magnitude of ChAT-immunoreactive neuronal loss within the medial septum and
      the age at which the lesion was made were inversely correlated (r2 = 0.887),
      indicating that cholinergic septal neurons become less vulnerable to target
      removal as the cells develop. Similar results were observed in the vertical limb
      of the diagonal band although a small but significant loss of ChAT-immunoreactive
      neurons was seen in this structure ipsilateral to the hippocampal lesion when
      lesions were performed on Postnatal Day 28. At all age groups, many remaining
      cholinergic septal/diagonal band neurons appeared dystrophic with stunted fiber
      outgrowth. The present study demonstrates that unlike adult rats, removal of
      hippocampal target neurons during development alters the viability and morphology
      of cholinergic neurons of the medial septum and diagonal band. This suggests that
      target neurons which synthesize endogenous neurotrophins are needed for normal
      development of cholinergic basal forebrain neurons, but may not be required for
      the normal maintenance of the adult cell.

PMID- 7521304
TI  - Src-related protein tyrosine kinases are physically associated with the surface
      antigen CD36 in human dermal microvascular endothelial cells.
AB  - Src-related cytoplasmic PTKs are physically and functionally associated with cell
      surface receptors and are involved in signal transduction. In this paper we
      report the identification of src-related proteins p59fyn, pp60c-src and p62yes in
      human microvascular endothelial cells cultured from normal human skin and their
      physical association with the thrombospondin receptor CD36. Such an association
      represents a potential signalling pathway by which thrombospondin may regulate
      angiogenesis.

PMID- 7521303
TI  - Point sources of Schwann cells result in growth into a nerve entubulation repair
      site in the absence of axons: effects of freeze-thawing.
AB  - Axonal regeneration in the peripheral nervous system requires the comigration of
      Schwann cells along with or ahead of the growing neurites. The present studies
      were undertaken to elucidate some of the parameters that influence Schwann cell
      migration into a nerve wound site. We used a modification of an entubulation
      repair model with two isolated segments of denervated nerve to show that Schwann
      cells in vivo can bridge a 10-mm distance in the absence of axons. Two pieces of
      isolated nerve served as point sources of Schwann cells. A crucial finding was
      that in order for Schwann cells to bridge this distance both isolated/denervated
      nerve stumps had to be living. In cases where one nerve stump was frozen Schwann
      cells were not able to bridge the gap distance, although other cell types made up
      a tissue bridge between both stumps. We have further shown that as Schwann cells
      grow into this nerve wound site they stain intensely for the low-affinity NGF
      receptor p75NGFR. Related in vitro experiments showed that Schwann cells actively
      migrate on cryostat sections of either intact or previously lesioned sciatic
      nerve, suggesting that they can grow on either axon-containing or axonless areas
      of nerve tissue. Contrary to migration on sciatic nerve, although Schwann cells
      attached and survived on cryostat sections of optic nerve, they did not migrate
      on this substrate. The results of the present experiments suggest that Schwann
      cells can respond to specific diffusible and substrate bound signals which
      influence their migration into a nerve repair site.

PMID- 7521305
TI  - Endogenous DHP-sensitive Ca(2+) channels in Pleurodeles oocytes.
AB  - The double electrode voltage-clamp technique was used to study voltage-dependent
      Ca(2+) channels in Pleurodeles oocytes. From a holding potential of -80 mV, Ba
      current (IBa) (recorded in Cl-free solution, Ba(2+ = 40 mM) activated at -36.7 +/
      4 mV, peaked at -11.6 +/- 4 mV and reversed at 55 +/- 7 mV (n = 24). This
      current activated slowly (rise time was 0.98 +/- 0.2 s;n = 14 at -10 mV) and was
      not inactivated. Cadmium (Cd(2+), 500 microM) completely inhibited I(Ba). The
      effect of Cd(2+) was dose-dependent (EC(50) = 37 +/- 5 microM; n = 5). Moreover,
      IBa was insensitive to omega-conotoxin (10 microM) but interestingly this I(Ba)
      displayed dihydropyridine (DHP) sensitivity. Bay K 8644 (5 microM), a DHP
      activator, increased the peak current amplitude in a dose-dependent manner
      (EC(50) = 5.9 +/- 0.6 microM; n = 10) and shifted the threshold and the maximum
      of current/voltage relationship towards negative potentials by -10 mV. Nifedipine
      (5 microM), a DHP antagonist, decreased I(Ba) by 80% at HP of -80 mV (EC(50) =
      1.2 +/- 0.2 microM; n = 6). We concluded that Pleurodeles oocytes possess High
      Voltage Activated Ca(2+) channels with properties similar to L-type Ca(2+)
      channels.

PMID- 7521306
TI  - Colocalization of neuropeptides with calbindin D28k and NADPH diaphorase in the
      enteric nerve plexuses of normal human ileum.
AB  - BACKGROUND/AIMS: The chemical coding of enteric neurons differs significantly
      among species. In the present study, the innervation of normal human ileum was
      characterized with respect to its chemical coding. METHODS: The submucosa was
      subdivided into zones 1-3 based on its thickness and distribution of ganglia. The
      neuropeptides, calbindin D28k, and protein gene product 9.5 were identified by
      immunocytochemistry. Nitric oxide production was identified by nicotinamide
      adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. RESULTS:
      Protein gene product 9.5 staining indicated that cell bodies of the submucosa
      could be subdivided into zones 1-3. Two major groups of submucosal cell bodies
      contained either substance P/somatostatin/calcitonin gene-related peptide or
      vasoactive intestinal peptide/neuropeptide Y/calbindin D28k. Gastrin-releasing
      peptide-containing cell bodies also colocalized with a subgroup of somatostatin
      cell bodies. No galanin, met-enkephalin, or NADPH diaphorase-positive cell bodies
      were present. In the myenteric plexus, the two major groups of cell bodies
      contained either calbindin or NADPH diaphorase. A proportion of the latter group
      costained with vasoactive intestinal peptide and met-enkephalin. Cell bodies
      containing substance P, somatostatin, and calcitonin gene-related peptide were
      present, forming three different subgroups. CONCLUSIONS: Of the species
      investigated to date, the chemical coding of human ileal cell bodies most closely
      resembles that of the rat.

PMID- 7521307
TI  - Abnormal basement membrane in tumors induced by rat colon cancer cells.
AB  - BACKGROUND/AIMS: Colonic mucosa basement membrane results from a cooperation
      between epithelial cells and pericryptal fibroblasts characterized as
      myofibroblasts. This cooperation may be abnormal in colorectal carcinoma
      resulting in basement membrane alteration. METHODS: Basement membrane composition
      and myofibroblast distribution were studied in normal rat colon and two colon
      carcinoma models by immunohistochemistry. Colon cancer cells and tumor-associated
      myofibroblasts were also studied for their capacity to deposit three basement
      membrane components (laminin, heparan sulfate proteoglycan, and type IV collagen)
      in vitro. RESULTS: A continuous, type IV collagen-containing basement membrane,
      such as that observed in normal colon, was found only in the most differentiated
      tumor model and was restricted to the areas in which myofibroblasts were closely
      apposed to carcinoma cells. In other areas of this tumor and in the poorly
      differentiated tumor model, myofibroblasts dissociated from the epithelial cells
      and the basement membrane was devoid of type IV collagen. In vitro, carcinoma
      cells deposited laminin and heparan sulfate proteoglycan but not type IV
      collagen. Tumor-associated myofibroblasts deposited type IV collagen only in the
      presence of tumor cell extracellular matrix or laminin coating. CONCLUSIONS: The
      colon cancer basement membrane defect in type IV collagen may result from a
      physical disruption in the association between epithelial cancer cells and
      myofibroblasts.

PMID- 7521308
TI  - A pilot study of combination therapy with ribavirin plus interferon alfa for
      interferon alfa-resistant chronic hepatitis C.
AB  - BACKGROUND/AIMS: In chronic hepatitis C, interferon alfa (IFN-alpha) therapy
      fails to achieve a sustained response in approximately 75% of patients.
      Similarly, ribavirin induces only a transient response. The aim of this study was
      to evaluate whether ribavirin and IFN-alpha in combination could be effective in
      IFN-alpha-resistant chronic hepatitis C. METHODS: Twenty patients with chronic
      hepatitis C resistant to a previous course of IFN-alpha were randomly assigned to
      receive either ribavirin combined with IFN-alpha or IFN-alpha alone for 6 months.
      RESULTS: Serum alanine aminotransferase levels decreased significantly during
      therapy in both treatment groups, but after therapy, the levels remained
      significantly decreased only in the combination therapy group. Nine months after
      treatment, sustained normalization of aminotransferase levels, associated with
      sustained loss of serum hepatitis C virus RNA, was observed in 40% of the
      patients in the combination therapy group but in none of the patients treated
      with IFN-alpha alone (P < 0.05). The sustained response was accompanied by
      reduced hepatic necroinflammatory activity on biopsy. CONCLUSIONS: These findings
      suggest that ribavirin plus IFN-alpha combination therapy is able to induce a
      sustained biochemical and virological response in a significant proportion of
      patients with IFN-alpha-resistant chronic hepatitis C.

PMID- 7521309
TI  - Ribosomal RNA gene (rrn) organization in enterococci.
AB  - A cloned 1.8-kb probe containing the 3' end of 16S ribosomal RNA and the 5' end
      of 23S ribosomal RNA from Enterococcus hirae was used to analyze various
      endonuclease digests of enterococci. In the ATCC strains tested we observed a
      remarkable conservation of the ApaI sites in the rrn operons, and a partial
      conservation of EcoRI sites. Using a number of other endonuclease digestions with
      the ApaI rrn probe, we estimate the number of rrn operons in enterococci to be
      between five and six.

PMID- 7521311
TI  - [Prostatic hyperplasia--alternative treatment with the laser].

PMID- 7521310
TI  - Epitope mapping by cysteine mutagenesis: identification of residues involved in
      recognition by three monoclonal antibodies directed against LamB glycoporin in
      the outer membrane of Escherichia coli.
AB  - Site-directed mutagenesis of the lamB gene was used to introduce individual
      cysteine substitutions at 20 sites in two regions (surface loops L7 and L8) of
      LamB protein significant in antibody recognition. Characterisation of cysteine
      mutants involved immunoblotting with three surface-specific monoclonal antibodies
      (mAb72, mAb302, mAb347) before and after incubation with thiol-specific reagents.
      In contrast to an earlier study that showed no amino acid changes affecting
      recognition by all three antibodies, changes at six amino acids were found to
      influence a common core epitope. These core sites included one residue (T336) in
      the predicted loop L7 containing amino acids 329-342 and four (Y379, N387, N389,
      K392, F398) in the large surface loop involving residues 370-412. Individual
      antibodies made additional but distinct contacts within the two studied regions,
      with mAb347 binding the most different and affected by seven substitutions in the
      328-338 regions. The lamB mutants were also tested for phage lambda receptor
      activity and starch binding before and after thiol modification and were useful
      in extending previous maps of these ligand binding sites.

PMID- 7521312
TI  - Detection and distribution of hepatitis C-specific antigens in naturally infected
      liver.
AB  - Hepatitis C virus antigen expression was examined using peptide antibodies in
      liver tissue taken at biopsy from four chronic carriers of hepatitis C virus.
      Hepatitis C virus antigens E2/NS1, NS3, NS4 and NS5 were widespread in unfixed
      frozen liver sections and were present as distinct granules or foci within the
      cytoplasm of hepatocytes and in infiltrating lymphocytes in portal tracts.
      Fixation of frozen sections with 1% formalin improved the histological appearance
      of the tissue section without reducing the sensitivity of antigen detection.
      However, in tissue sections fixed in acetone, chloroform, carbon tetrachloride or
      methyl carnoys, detection of all hepatocyte-specific hepatitis C virus antigens
      was significantly reduced. Dual immunostaining of liver sections for lymphocyte
      cluster of differentiation markers and hepatitis C virus antigens determined that
      a high proportion of cluster of differentiation 20-positive B cells and cluster
      of differentiation 4-and cluster of differentiation 8-positive T cells,
      predominant in lymphoid aggregates, were positive for hepatitis C virus antigens.

PMID- 7521313
TI  - A multicenter randomized controlled dose study of ursodeoxycholic acid for
      chronic hepatitis C.
AB  - The effect of ursodeoxycholic acid on liver function tests and on bile acid
      metabolism was investigated in a multi-center randomized controlled dose study
      for chronic hepatitis C. Twenty, 18 and 19 patients were administered 150, 600
      and 900 mg/day, respectively of ursodeoxycholic acid every day for 16 wk. Serum
      liver parameters and bile acid composition in the treatment groups were compared
      with 17 control patients. A similarly significant decrease of serum alanine
      aminotransferase and serum gamma-glutamyltransferase was observed in patients
      administered 600 and 900 mg of ursodeoxycholic acid. Serum bile acid composition
      was determined by high-performance liquid chromatography. At entry, the relative
      proportions of major bile acids were similar to those observed in normal
      individuals. Maximal concentrations of total ursodeoxycholic acid were 0.30
      mumol/L, 5.59 mumol/L, 21.42 mumol/L and 14.73 mumol/L in the control, 150, 600
      and 900 mg/day groups, respectively. The fraction of the total ursodeoxycholic
      acid increased in a dose-dependent manner, and it was significantly higher than
      in controls (p < 0.001). The hydrophobicity index of bile acids was calculated by
      the method of Heuman, and its correlation with serum parameter levels was
      analyzed. In the 600 and 900 mg/day dose groups, serum alanine aminotransferase
      decreased in the cases in which hydrophobicity index significantly decreased
      during treatment. The same correlation was observed between the hydrophobicity
      index and serum gamma = glutamyltransferase in these two groups. There was no
      correlation between these parameters in the control and 150-mg groups. There was
      no correlation between reduction rate of serum alanine aminotransferase and
      initial liver histology.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521315
TI  - Appearance of sinusoidal inclusion-containing endothelial cells in liver disease.
AB  - Sinusoidal "inclusion-containing endothelial cells" were studied
      histopathologically and immunohistochemically in various liver diseases, and
      their clinical importance was investigated. A total of 498 needle liver biopsies
      were examined. Endothelial inclusions inside the cells were recognized as
      eosinophilic granules in hematoxylin-eosin-stained sections. Electron microscopy
      showed that these inclusions corresponded to round cytoplasmic dense bodies with
      a single limiting membrane. The contents of these bodies were generally
      homogeneous, but sometimes heterogeneous. The inclusions appeared to contain
      protein, but were resistant to trypsin digestion, and immunohistochemistry failed
      to identify any immunoglobulins or hepatocyte-derived proteins. These endothelial
      cells also contained an increased number of micropinocytotic vesicles when
      compared with ordinary cells. The inclusion-containing endothelial cells appeared
      frequently in chronic hepatitis, but were relatively rare in other liver
      diseases. The incidence was higher in chronic aggressive hepatitis than in
      chronic persistent hepatitis or inactive cirrhosis. Although the density of these
      cells varied considerably even among patients with the same histological
      diagnosis and the phenotypical changes of these endothelial cells, assessed by
      monoclonal antibodies, were not apparent, the serum gamma globulin level tended
      to increase in relation to the density of inclusion-containing endothelial cells
      and the correlation was significant in hepatitis C.

PMID- 7521316
TI  - Phase II study of transarterial embolization in European patients with
      hepatocellular carcinoma: need for controlled trials.
AB  - Our uncontrolled phase II study was aimed at assessing the efficacy of
      transarterial embolization in patients with hepatocellular carcinoma and to
      determine the parameters associated with a favorable response to treatment,
      improved survival or both. Fifty consecutive patients (25 corresponding to
      Okuda's stage I and 25 to stage II) with hepatocellular carcinoma (41 being
      multinodular or massive) were included. Transarterial embolization induced a self
      limited postembolization syndrome that was well tolerated. Nevertheless, three
      patients died shortly after the procedure because of tumor progression (two
      cases) or progressive liver failure. A favorable response (extensive necrosis
      with reduction of tumor area greater than 50%) was achieved in 81% of the cases,
      and this result was independently (p < 0.05) related to a preserved performance
      status and to a lower alpha-fetoprotein concentration. The survival of the
      patients at 1 and 2 yr was 65% and 38%, respectively, better than the expected
      survival according to a mathematical model obtained from a historical series of
      untreated cases (42% and 20%, respectively). Cox regression analysis disclosed
      that both a favorable therapeutic response and a preserved physical condition
      (reflected by performance status of 0 or 1) were independently associated with
      better survival (regression coefficient -2.248 and 0.869, respectively). These
      data indicate that transarterial embolization has a marked antitumoral effect in
      patients with inoperable hepatocellular carcinoma and that the therapeutic
      success is associated with improved survival. Nevertheless, because the potential
      benefit for survival observed in this uncontrolled study appears to be moderate,
      prospective controlled trials to ascertain the real usefulness of this
      therapeutic approach are mandatory.

PMID- 7521314
TI  - Heterogeneity of combinatorial human autoantibodies against PDC-E2 and biliary
      epithelial cells in patients with primary biliary cirrhosis.
AB  - The polyclonal nature of antimitochondrial autoantibodies and the limited success
      of generating human monoclonal antibodies have made analysis of fine specificity
      and antibody heterogeneity difficult to define. The major autoantigen of primary
      biliary cirrhosis is the E2 component of the pyruvate dehydrogenase pathway (PDC
      E2). To address the relative importance of the region(s) in the PDC-E2 inner
      lipoyl domain to antibody binding, we report herein detailed profiles of 12 PDC
      E2-specific antigen-binding fragments, SP1 through SP12, derived by screening of
      a combinatorial immunoglobulin library (derived from a primary biliary cirrhosis
      patient) with full-length native PDC-E2. All antigen-binding fragments are IgG
      isotypes and include a similar number of lambda- and kappa-chains. The antigen
      binding fragments react specifically to PDC-E2 with high affinity (kappa a = 10(
      7) to 10(-10) mol/L-1) and recognize a conformational epitope in the inner lipoyl
      domain of PDC-E2. Furthermore, the antibodies demonstrate substantial
      heterogeneity in recognition of different recombinant PDC-E2 fragments and
      differential recognition patterns against mutant constructs of the human PDC-E2
      inner lipoyl domain (amino acid residues 91 to 227). In addition, five of the
      antigen-binding fragment clones (SP1, 3, 4, 8 and 12) demonstrate different
      staining patterns on biliary epithelial cells of patients with primary biliary
      cirrhosis but not control liver disease; some antigen-binding fragments
      specifically stained the apical region of biliary epithelium, a pattern distinct
      from that of typical mitochondrial staining. The response to the inner lipoyl
      domain is not, however, monospecific, and there is much more heterogeneity in
      fine specificity than could be accounted for by arbitrary reshuffling of variable
      immunoglobulin heavy and light chains into unnatural combinations.

PMID- 7521317
TI  - The eosinophil as an effector cell of the immune response during hepatic
      allograft rejection.
AB  - OBJECTIVE: To evaluate the role of the eosinophil granulocyte during hepatic
      allograft rejection. DESIGN: (a) A retrospective case-control study and (b) a
      prospective study of consecutive liver transplant recipients. PATIENTS: In the
      retrospective study, eight patients with severe rejection in the first month
      after liver transplantation were compared with six patients without rejection. In
      the prospective study, 20 consecutive patients were studied for the presence of
      liver allograft rejection between March 1989 and October 1989. MEASUREMENTS:
      Absolute eosinophil counts were determined whenever blood was drawn. Serum was
      analyzed for the presence of two eosinophil granule proteins, major basic protein
      and eosinophil-derived neurotoxin, on days 7, 14 and 21 after transplantation.
      Liver biopsy specimens were stained for the presence of major basic protein by
      means of immunofluorescence using a double-antibody staining technique. The
      degree of eosinophil infiltration and degranulation was graded using a panel of
      representative slides. RESULTS: Blood eosinophilia was increased in patients with
      hepatic allograft rejection (p < 0.05). Serum major basic protein and eosinophil
      derived neurotoxin concentrations were similar in patients with and without
      rejection. Many portal tracts of patients with rejection contained an abundance
      of eosinophils, and staining for major basic protein revealed the presence of
      intact eosinophils. In addition, extracellular major basic protein was seen,
      sometimes in the absence of intact eosinophils or an extensive infiltrate. In
      patients with severe allograft rejection, major basic protein staining was
      present in littoral cells lining the sinusoids. CONCLUSIONS: Patients with severe
      rejection in the first month after liver transplantation often have blood
      eosinophilia and marked infiltration of portal tracts with eosinophils or
      evidence of eosinophil degranulation. The presence of major basic protein likely
      is direct evidence of tissue destruction and may indicate active rejection (major
      basic protein in eosinophils and extracellular major basic protein, presence of
      portal infiltrate) or the immediate postinflammatory rejection state
      (extracellular major basic protein and major basic protein inside littoral cells,
      absence of portal infiltrate and eosinophils, bile ducts damaged or vanished).
      These findings underline the importance of the eosinophil as an integral part of
      the rejection process. We conclude that the presence of eosinophils or their
      secretion products in the first month after liver transplantation is an indicator
      of ongoing or recent allograft rejection.

PMID- 7521319
TI  - Hepatitis C virus: from epidemiology and molecular virology to immunobiology.

PMID- 7521318
TI  - Posttranslational events involved in griseofulvin-induced keratin cytoskeleton
      alterations.
AB  - Alcoholic hepatitis is a disease associated with profound alterations of the
      hepatocytic intermediate filament cytoskeleton. Similar cytoskeletal alterations
      can be induced in mice with prolonged feeding of the fungistatic drug
      griseofulvin. Murine hepatocytic intermediate filaments are composed of equimolar
      amounts of keratin polypeptides A (type II) and D (type I). Griseofulvin
      intoxication of mice leads to diminution, derangement and even loss of the
      cytoplasmic keratin meshwork and formation of keratin-containing cytoplasmic
      inclusions, termed Mallory bodies. To study protein alterations leading to
      disturbance of keratin filament architecture, soluble keratin polypeptides and
      keratin filaments were purified from griseofulvin-damaged and control mouse
      livers. In griseofulvin-damaged livers, more acidic isoforms occurred in soluble
      keratin D, whereas the corresponding filaments had a polypeptide composition
      similar to that in controls. In vivo [32P]orthophosphate incorporation revealed
      that the shift of isoelectric forms toward more acidic spots was due to
      hyperphosphorylation of keratin D. The nature of the kinase(s) involved has yet
      to be elucidated. In addition, rapid proteolysis only of soluble keratin A was
      detected in vitro, and there is evidence for increased proteolysis in
      griseofulvin damage in vivo. The enzyme involved has features of a calpain-type
      protease. Posttranslational modifications play a substantial role in the
      disturbance of keratin intermediate filament homeostasis in vivo.

PMID- 7521320
TI  - The role of inflammatory mediators on hepatitis B virus surface expression in a
      transgenic mouse model.

PMID- 7521321
TI  - CFTR mutations in Chilean cystic fibrosis patients.
AB  - An analysis of five of the most common cystic fibrosis (CF) mutations worldwide
      (delta F-508, R-553X, G-551D, N-1303K and G-542X) was performed in 36 Chilean
      patients. Polymerase chain reaction (PCR) amplification of the DNA followed by
      allele specific restriction enzyme analysis was used for detection. The overall
      frequencies of the mutations in the chromosomes analyzed were 29.2% for delta F
      508 and 4.2% for R-553X (n = 72). The G-542X, G-551D and N-1303 K mutations were
      absent in the Chilean sample. Our data suggest however that delta F-508 is not
      the most common CF mutation in Chilean patients. delta F-508 and R-553X account
      for only 33.4% of the alleles; 66.6% of them do not respond to the probes used
      and still remain uncharacterized.

PMID- 7521323
TI  - Neonatal pain.

PMID- 7521322
TI  - Skipping of multiple CFTR exons is not a result of single exon omissions.
AB  - The omission of complete exons in a proportion of mature transcripts has been
      shown for a variety of genes. In the case of the cystic fibrosis transmembrane
      conductance regulator gene, this phenomenon has previously been observed for
      exons 4, 9 and 12. Here, we describe the detection of a combined skipping of
      exons 11 and 12 in the absence of detectable transcripts missing only exon 11.
      This constellation has been found both in peripheral blood cells and in
      specifically expressing lung tissue, and excludes the possibility that the
      simultaneous skipping of both exons is merely a stochastic combination of single
      exon skipping events.

PMID- 7521324
TI  - Metastatic extragonadal germ cell tumor.

PMID- 7521325
TI  - Clara cell 10 kDa protein mRNA in normal and atypical regions of human
      respiratory epithelium.
AB  - We used RNA-RNA in situ hybridization to study expression of the human CC10 gene
      in morphologically normal and atypical areas of 32 non-neoplastic lung specimens
      resected from 26 non-small cell lung cancer patients. We scored strong, moderate
      or weak levels of CC10 mRNA expression in 3 distinct lung compartments. In
      morphologically normal lungs, strong and moderate levels of CC10 mRNA were
      observed in bronchioli and bronchi, respectively, but the expression was rarely
      observed in the alveolar region. Distinct alterations in CC10 mRNA expression
      were noted in specific histologic abnormalities within bronchi and the alveolar
      region. CC10 hybridization signal decreased markedly in bronchi containing
      diffuse goblet cell hyperplasia or squamous metaplasia, while CC10 mRNA
      expression remained unchanged in bronchi with basal cell hyperplasia or focal
      goblet cell hyperplasia. Bronchiolar CC10 mRNA levels remained unchanged in
      sections containing abnormalities elsewhere. Interestingly, in alveoli with
      bronchiolization of the alveoli, high levels of CC10 mRNA were observed. These
      regions also contained strongly stained keratin 14-positive cells, which may
      indicate a concurrent metaplastic process. In lungs with morphologic atypias, no
      correlation was found between abnormalities detected in bronchi and alveoli from
      the same lung. A comparison of mRNA expression and clinicopathologic features
      demonstrated that the amount of histologic abnormalities increased with smoking
      history (pack years); however, no correlation between CC10 mRNA expression and
      sex, age or smoking history was found.

PMID- 7521327
TI  - The potential benefits of serotonin receptor-specific agents.
AB  - Antidepressant drugs are effective for about three in four people with
      depression. For reasons that are not understood, individual patients who do not
      respond to one drug often respond to another. Differences in mechanisms of action
      may thus be important in determining treatment success or failure. In addition to
      efficacy, drug side effect profile also determines treatment outcome. In general,
      the fewer or less severe the side effects of a drug, the greater the degree of
      compliance with treatment. A major consequence of the introduction of selective
      serotonin-specific antidepressants is greater patient acceptance due to fewer
      side effects. Still, some patients are unable to tolerate the nervousness,
      insomnia, or sexual dysfunction associated with these drugs. Drugs that are even
      more specific in that they act on specific serotonin receptor subtypes, rather
      than only by blocking serotonin uptake, may provide efficacy and fewer side
      effects for patients who do not respond to or tolerate less specific agents.

PMID- 7521326
TI  - Dopamine antagonists in tic-related and psychotic spectrum obsessive compulsive
      disorder.
AB  - Serotonin uptake inhibitors (SUIs) have been established as the first-line
      pharmacotherapy of obsessive compulsive disorder (OCD). However, approximately
      one half of patients who receive an adequate trial with these agents remain
      clinically unchanged. The addition of drugs that enhance serotonin (5-HT)
      neurotransmission, such as lithium and buspirone, to ongoing treatment in SUI
      refractory patients has generally proved to be an ineffective strategy. The
      addition of dopamine antagonists to the regimens of SUI-resistant patients
      appears to be a useful approach for OCD patients with a comorbid chronic tic
      disorder (e.g., Tourette's syndrome) and possibly for those with concurrent
      psychotic spectrum disorders. These drug response data suggest that both the 5-HT
      and dopamine systems may be involved in the treatment, and possibly the
      pathophysiology, of specific subtypes of OCD.

PMID- 7521328
TI  - Mitochondrial DNA variation in human populations and implications for detection
      of mitochondrial DNA mutations of pathological significance.
AB  - Haplotype and phylogenetic analyses of "normal" mitochondrial DNAs (mtDNAs) have
      allowed a clarification of several controversial issues concerning the origin of
      humans, the time and colonization pattern of the various regions of the world,
      and the genetic relationships of modern human populations. More recently, the
      same type of analyses has also been applied to mtDNA disease studies. A review of
      these studies indicates that exhaustive screenings of "normal" mtDNA variation in
      all human populations associated with haplotype and phylogenetic analyses are
      essential if we are to understand the etiology of mitochondrial pathologies.

PMID- 7521329
TI  - Mutational analysis of the helical hairpin region of diphtheria toxin
      transmembrane domain.
AB  - Entry of the catalytic domain of diphtheria toxin into the cytoplasma of
      eukaryotic cells depends on insertion of the T (transmembrane) domain into the
      endosomal membrane, a process triggered by low pH. To probe the mechanism of
      insertion, we mutated ionizable residues within the helical hairpin region of the
      T domain. Only three mutations caused significant effects on cytotoxicity, D295K,
      E349K, and D352K. Each of these represents a substitution of a basic for an
      acidic residue at the tip of a helical hairpin. Substitution of Lys for Glu349 or
      Asp352, in the TH8/9 hairpin, reduced toxicity for Vero cells > 100-fold, whereas
      a Lys substitution for Asp295, one of 3 acidic residues in the TH5/6/7 hairpin,
      caused a less marked reduction. All three mutations also altered the pH-dependent
      formation, and/or ion conductance, of channels formed by the toxin in artificial
      bilayers or the plasma membrane. E349K or D352K did not alter the pH dependence
      of conformational changes in the toxin occurring near pH 5. Our findings support
      the hypothesis that the TH8/9 hairpin inserts into the endosomal membrane after
      low pH-mediated partial unfolding of the T domain. A positive residue at the tip
      of this hairpin apparently inhibits insertion and blocks toxin action. The ion
      conducting properties of channels formed by selected mutants, described
      elsewhere, are consistent with this model. The status of the TH5/6/7 hairpin in
      the integral membrane form of the T domain remains uncertain.

PMID- 7521330
TI  - Identification of calmodulin-, Ca(2+)-, and ruthenium red-binding domains in the
      Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic
      reticulum.
AB  - cDNAs encoding trpE fusion proteins containing fragments of the skeletal muscle
      Ca2+ release channel (ryanodine receptor) were expressed in bacteria. The fusion
      proteins, which covered about 90% of the linear sequence of the ryanodine
      receptor, were used to identify calmodulin- (CaM), Ca(2+)-, and ruthenium red
      binding regions in the ryanodine receptor through the use of 125I-CaM, 45Ca2+,
      and ruthenium red overlay procedures. Six Ca(2+)-dependent CaM-binding domains
      were detected in the skeletal muscle ryanodine receptor. Strong CaM-binding
      domains were localized in regions 6, 11, 12, and 13, in subregions 6b, 11b, and
      13b, and in short sequences 6b3, 11b1, and 13b2, lying between amino acid
      residues 2063 and 2091, 3611 and 3642, and 4303 and 4328. Weaker CaM-binding
      domains were localized in regions 4, 9, and 10 and in subregions 4b, 9b, and 10a,
      lying between residues 921 and 1173, 2804 and 2930, and 2961 and 3084. Most of
      these CaM-binding domains encompassed all or part of previously predicted CaM
      binding sites. Strong 45Ca(2+)- and ruthenium red-binding sites domains were
      localized in the NH2- and COOH-terminal regions of the ryanodine receptor and in
      regions 6, 12, and 13. The 45Ca(2+- and ruthenium red-binding sites in regions 6
      and 12 were localized in subregions 6b and 12b, lying between residues 1861-2094
      and 3657-3776. These data together with earlier studies (Chen, S. R. W., Zhang,
      L., and MacLennan, D. H. (1992) J. Biol. Chem. 267, 23318-23326), show that
      strong CaM-, Ca(2+)-, and ruthenium red-binding domains are colocalized in the
      skeletal muscle ryanodine receptor.

PMID- 7521331
TI  - Involvement of phosphatidylinositol 3-kinase in Fc gamma receptor signaling.
AB  - Wortmannin, a potent and selective inhibitor of phosphatidylinositol (PI) 3
      kinase (Okada, T., Sakuma, L., Fukui, Y., Hazeki, O., and Ui, M. (1994) J. Biol.
      Chem. 269, 3563-3567), prevented Fc receptor for IgG (Fc gamma R)-dependent
      phagocytosis of the human monocytic cell line U937 or guinea pig neutrophils.
      Cross-linking of Fc gamma R on the surface of U937 cells increased PI 3-kinase
      activity that was immunoprecipitated with antibody against phosphotyrosine or
      antibody against the 85-kDa regulatory subunit of PI 3-kinase. Specific cross
      linking of Fc gamma R subclass Fc gamma RI or Fc gamma RII, using monoclonal
      antibodies against each receptor subclass and the F(ab')2 fragment of goat
      antibody against mouse IgG, increased anti-phosphotyrosine-precipitable PI 3
      kinase activity. Treatment of cells with anti-Fc gamma RIII antibody plus the
      same F(ab')2 did not affect the activity, reflecting the lack of Fc gamma RIII in
      U937 cells. Fcy gamma R stimulation triggered prominent tyrosine phosphorylation
      of several proteins, among which the 115-kDa peptide showed strong association
      with PI 3-kinase. Thus, Fc gamma R appears to be coupled functionally, via a
      tyrosine kinase, to PI 3-kinase, which may regulate the phagocytotic activity of
      the cells.

PMID- 7521332
TI  - The role of the I domain in ligand binding of the human integrin alpha 1 beta 1.
AB  - We report here the analysis of potential ligand binding domains within the human
      integrin alpha 1 subunit, a known collagen/laminin receptor. This integrin is
      effectively blocked by the mouse monoclonal antibody 1B3.1. A truncated version
      of the alpha 1 subunit lacking the NH2-terminal half of the extracellular domain
      is not recognized by monoclonal antibody 1B3.1. Furthermore, we have isolated a
      cDNA containing the I domain from chicken alpha 1 bearing significant homology to
      the human and rat alpha 1 sequences. Replacing the human I domain with its
      chicken counterpart led to the surface expression of a functional heterodimer
      with endogenous mouse beta 1 on NIH 3T3 cells. However, 1B3.1 does not bind to
      the chicken/human chimera, demonstrating that the human alpha 1 I domain is
      required for epitope recognition. Mutation of Asp253 within the I domain to
      alanine resulted in surface expression of an alpha beta heterodimer recognized by
      1B3.1 but with markedly reduced binding to collagen IV or laminin. Since a
      previously reported mutation of a homologous Asp in the Mac-1 I domain has
      similar consequences, these results suggest a central role for the I domain in
      ligand recognition for all integrin alpha subunits containing this domain.

PMID- 7521333
TI  - Intramolecular and extramolecular mechanisms repress the catalytic function of
      p56lck in resting T-lymphocytes.
AB  - Accumulating data show that the catalytic function of the Src-related tyrosine
      protein kinase p56lck is repressed by phosphorylation of a conserved carboxyl
      terminal tyrosine residue (tyrosine 505). However, previous findings (Abraham,
      N., Miceli M.C., Parnes, J.R., and Veillette, A. (1991) Nature 350, 62-66)
      suggest that mechanisms unrelated to tyrosine 505 phosphorylation repress the
      catalytic function of p56lck in resting T-cells. In keeping with this view, we
      report herein that the Src homology 3 (SH3) and SH2 domains negatively regulate
      the catalytic activity of p56lck, by a process independent of carboxyl-terminal
      tyrosine phosphorylation. While the exact mechanism of this inhibition are not
      established, its structural requirements in the SH2 domain are distinct from
      those allowing recruitment of Lck in T-cell receptor signaling. In addition, we
      obtained evidence that the elevated tyrosine protein phosphatase activity present
      in T-cells also contributes to inhibit the enzymatic function of p56lck. Such an
      effect is seemingly mediated by dephosphorylation of tyrosine 394, the site of
      positive regulation of p56lck. Collectively, these results indicate that the
      catalytic function of p56lck in resting T-cells is repressed by a complex set of
      processes, which involves both intramolecular and extramolecular mechanisms.

PMID- 7521335
TI  - Homomeric interactions between type II transforming growth factor-beta receptors.
AB  - Transforming growth factor-beta (TGF-beta) binds with high affinity to three cell
      surface receptors. Both type I and II receptors are transmembrane
      serine/threonine kinases and thought to mediate TGF-beta responses by forming a
      heteromeric complex in the presence of TGF-beta. We investigated whether the type
      II receptors form a homomeric complex in the presence or absence of ligand.
      Double immunoprecipitation analyses were performed using lysates from
      metabolically labeled cells cotransfected with differentially epitope-tagged type
      II receptors. We demonstrate that the type II receptors can form a homomeric
      complex even in the absence of their ligand, TGF-beta. This pre-existing type II
      receptor complex has the ability to bind TGF-beta. Moreover, in addition to the
      extracellular and transmembrane domains, the cytoplasmic portions of the
      receptors are also able to interact with each other, indicating that multiple
      contact points are involved in the formation of the homomeric type II receptor
      complex. Our results suggest a novel mechanism of complex formation and receptor
      activation of the serine/threonine kinase receptor family.

PMID- 7521334
TI  - A yeast metal resistance protein similar to human cystic fibrosis transmembrane
      conductance regulator (CFTR) and multidrug resistance-associated protein.
AB  - Members of the ATP binding cassette (ABC) protein superfamily transport a variety
      of substances across biological membranes, including drugs, ions, and peptides.
      The yeast cadmium factor (YCF1) gene from Saccharomyces cerevisiae is required
      for cadmium resistance and encodes a 1,515 amino acid protein with extensive
      homology to both the human multidrug resistance-associated protein (MRP1) and the
      cystic fibrosis transmembrane conductance regulator (hCFTR). S. cerevisiae cells
      harboring a deletion of the YCF1 gene are hypersensitive to cadmium compared with
      wild type cells. Mutagenesis experiments demonstrate that conserved amino acid
      residues, functionally critical in hCFTR, play a vital role in YCF1-mediated
      cadmium resistance. Mutagenesis of phenylalanine 713 in the YCF1 nucleotide
      binding fold 1, which correlates with the delta F508 mutation found in the most
      common form of cystic fibrosis, completely abolished YCF1 function in cadmium
      detoxification. Furthermore, substitution of a serine to alanine residue in a
      potential protein kinase A phosphorylation site in a central region of YCF1,
      which displays sequence similarity to the central regulatory domain of hCFTR,
      also rendered YCF1 nonfunctional. These results suggest that YCF1 is composed of
      modular domains found in human proteins which function in drug and ion transport.

PMID- 7521336
TI  - Factor XII fragment and kallikrein generation in plasma during incubation with
      biomaterials.
AB  - Blood biocompatibility of medical devices is in many ways dependent on surface
      characteristics and biochemical blood material interactions. In this study, the
      contact system, in which the activation of factor XII and plasma kallikrein is
      included, is highlighted. This article describes a simple chromogenic assay to
      determine the Hageman Factor fragment (HFf, or factor XIIf) and kallikrein
      activity in vitro. The assay is based on conversion of Z-Lys-Phe-Arg-pNA.2HCl to
      which human factor XIIf and kallikrein appeared to have a high affinity. To
      discriminate between the serine proteases factor XIIf and kallikrein to cleave
      this substrate, aprotinin was added to one of two complementary samples. In this
      in vitro study, standardized disks from glass, high-density polyethylene (HDPE),
      polytetrafluoro ethylene (PTFE), and polydimethyl siloxane (PDMS) were studied
      for their capacity to generate factor XIIf and kallikrein in plasma. Kaolin was
      used as positive control. On glass disks the highest and on HDPE the lowest
      generation of factor XIIf and kallikrein were found, both with a ratio of 1:1. On
      PDMS and on PTFE disks protease activities were intermediate, but with a factor
      XIIf and kallikrein activity ratio of 1:2 and 1:4, respectively. Apparently
      because of the hydrophobic surface character of PDMS and PTFE, these surfaces
      absorb or fail to produce the factor XIIf. This assay appeared to be
      discriminative even for materials that are considered mild activators of the
      contact system and can therefore be used as a standard method to qualify
      biomaterials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521337
TI  - Prolonged peak elevations in cytoplasmic free calcium ions, derived from
      intracellular stores, correlate with the extent of thrombin-stimulated exocytosis
      in single human umbilical vein endothelial cells.
AB  - We have used indo-1-loaded human endothelial cells (EC) in monolayer culture and
      quantitative laser scanning fluorescence microscopy techniques to investigate the
      magnitude and duration of the change in cytoplasmic free calcium ([Ca2+]i)
      required for thrombin-stimulated von Willebrand factor (vWF) secretion in
      individual EC. Both alpha-thrombin and a 14 amino acid thrombin receptor
      activating peptide stimulate an increase in EC [Ca2+]i that is agonist dose
      dependent. Low-dose agonist treatment generates asynchronous oscillations (i.e.,
      repetitive spikes < 80 sec duration) in [Ca2+]i. Stimulation with higher agonist
      concentrations generates a prolonged single peak elevation in [Ca2+]i. Both the
      number of cells displaying prolonged [Ca2+]i peaks and the mean amplitude of the
      peaks increase as a function of agonist concentration. Higher doses of agonist
      also cause sustained elevations in [Ca2+]i that depend upon extracellular Ca2+.
      Oscillations in [Ca2+]i are not sufficient to stimulate significant vWF
      secretion, and sustained elevations in [Ca2+]i are not required for maximal
      secretion. Both the number of cells displaying prolonged peaks and the mean peak
      amplitude correlate with increasing levels of vWF secretion from the culture. We
      have used the expression of P-selectin, a secretory granule membrane protein, as
      a marker for measuring thrombin-induced exocytosis in individual EC. Both the
      number of secreting cells and the amount of secretion per cell increase as a
      function of thrombin concentration. The graded responses in [Ca2+]i amplitudes
      and the graded exocytotic response may be causally related.

PMID- 7521338
TI  - Concentrations of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3),
      IGF, and IGFBP-3 protease activity in cerebrospinal fluid of children with
      leukemia, central nervous system tumor, or meningitis.
AB  - Insulin-like growth factor-II (IGF-II) is the major IGF in human cerebrospinal
      fluid (CSF), whereas IGF-I is only detectable in trace amounts. The major IGFBPs
      in CSF are IGFBP-2 and IGFBP-4. Normally, IGFBP-3 is a minor component in CSF of
      healthy subjects, but may be increased in pathological states. We investigated
      IGF-I, IGF-II, and IGFBP-3 levels by specific RIAs in CSF from patients with
      central nervous system (CNS) tumor or leukemia and compared them with values in
      patients with meningitis. Further, as proteolysis of IGFBP-3 is part of the
      modulation of IGF activity, IGFBP-3 fragmentation was quantified by densitometric
      analysis of [125I]IGFBP-3 protease assays. We examined CSFs of 23 children with
      malignant CNS tumors, 18 children with leukemia, and 13 children with meningitis.
      The CSF from 38 children who received lumbar punctures to exclude meningitis was
      used to define the normal range for IGF-I, IGF-II, IGFBP-3, and IGFBP-3 protease
      activity in CSF. CNS tumor and leukemia patients had normal levels of IGF-I and
      IGF-II in CSF, whereas the IGF-II concentration in CSF of meningitis patients was
      elevated (P < 0.0001). Only 2 of 13 (15%) meningitis patients had elevation of
      CSF IGFBP-3 concentrations, despite high numbers of inflammatory cells. By
      comparison, elevated IGFBP-3 concentrations were found in the CSF of 16 of 23
      (70%) CNS tumor patients and 6 of 7 (86%) CNS tumor patients with microscopically
      detectable malignant cells in CSF. Twelve of 13 (92%) patients with
      medulloblastoma or ependymoma and all 7 medulloblastoma/ependymoma patients with
      malignant cells in CSF had elevated IGFBP-3 concentrations. The IGFBP-3 protease
      activity in CSF was elevated in 15 of 16 (94%) patients with CNS tumors of high
      grade histological malignancy. Five of 6 patients (83%) with acute leukemia and
      microscopically detectable malignant cells in CSF at the time of diagnosis showed
      elevated IGFBP-3 concentrations, with normalization after chemotherapy. Leukemia
      patients without malignant cells in CSF had normal IGFBP-3 concentrations. We
      conclude that in CSF of children with highly malignant CNS tumor or CNS leukemia,
      IGFBP-3 is elevated. This phenomenon could be caused by disruption of the blood
      CSF barrier and entry of IGFBP-3 from serum, although this appears unlikely,
      especially for CNS leukemia. More likely possibilities are 1) local production of
      IGFBP-3 by CNS tumor tissue and secretion into the CSF, or 2) local production of
      IGFBP-3 by malignant cells within the CSF.

PMID- 7521339
TI  - Glucagon stimulates insulin-like growth factor binding protein-1 secretion in
      healthy subjects, patients with pituitary insufficiency, and patients with
      insulin-dependent diabetes mellitus.
AB  - Glucagon (1-1.5 mg) was administrated iv as a bolus dose to healthy individuals
      (n = 7), patients with GH deficiency (n = 14), and patients with insulin
      dependent diabetes mellitus (IDDM; n = 6). Thereafter, blood samples for
      determination of serum glucose, insulin, insulin-like growth factor-binding
      protein-1 (IGFBP-1), GH, and insulin-like growth factor-I (IGF-I) concentrations
      were collected for 180 min. IGFBP-1 concentrations increased significantly in
      response to glucagon, with maximal values observed at 90 min [in healthy subjects
      from 36 +/- 6 to 58 +/- 10 micrograms/L (P < 0.05), in GH-deficient patients from
      36 +/- 4 to 54 +/- 6 micrograms/L (P < 0.001), and in IDDM patients from 115 +/-
      18 to 167 +/- 27 micrograms/L (P < 0.05)]. The IGFBP-1 elevation was delayed in
      relation to the glucagon-induced increase in glucose and insulin concentrations.
      When the groups were combined, the individual IGFBP-1 peak value observed at 90
      min was inversely correlated to the individual peak value of insulin observed at
      15-30 min (r = -0.743; P < 0.001). In GH-deficient patients, serum GH
      concentrations remained undetectable (< 0.2 micrograms/L), and IGF-I
      concentrations were unchanged after the glucagon injection. In healthy subjects
      and IDDM patients, mean GH levels did not change significantly, whereas mean IGF
      I concentrations decreased slightly at 30 min. In conclusion, glucagon increased
      serum IGFBP-1 concentrations in spite of increases in glucose and insulin. These
      results suggest that glucagon is a stimulator of IGFBP-1.

PMID- 7521340
TI  - Aging is associated with decreased suppression of insulin-like growth factor
      binding protein-1 by insulin.
AB  - We determined whether aging influences circulating insulin-like growth factor
      binding protein-1 (IGFBP-1) concentrations and, if so, whether this effect is
      explained by altered regulation of IGFBP-1 by insulin. Fasting levels of glucose,
      insulin, and IGFBP-1 were measured in 94 healthy volunteers, ages 24-93 yr. To
      determine the effect of aging on insulin-induced suppression of IGFBP-1, an oral
      glucose tolerance test (OGTT) was performed in 10 older (72-92 yr) and 10 younger
      (24-58 yr) nonobese subjects, matched for sex and body mass index. For all ages
      combined, the mean glucose level (+/- SE) averaged 4.9 +/- 0.1 mmol/L, and there
      was no significant change with aging. Fasting insulin and IGFBP-1 concentrations
      increased with advancing age (r = 0.37, P < 0.001 for age vs. insulin and r =
      0.47, P < 0.001 for age vs. IGFBP-1). However, there was no correlation between
      insulin and IGFBP-1 concentrations. In multiple linear regression analysis, the
      age-related increase in IGFBP-1 was independent of body mass index. During the
      OGTT, the mean insulin concentration was significantly higher in the older group
      compared with the younger group (P < 0.001). Serum IGFBP-1 concentrations were
      higher in the fasting state as well as during the OGTT, and the mean percent
      decrease of IGFBP-1 below baseline was significantly smaller in the older
      compared to the younger subjects at 3 h (35 +/- 5% vs. 55 +/- 2%, P < 0.01). We
      conclude that aging is associated with decreased suppression of serum IGFBP-1 by
      insulin, as demonstrated by 1) lack of the inverse correlation between fasting
      insulin and IGFBP-1 seen in young adults; 2) concurrent elevation of fasting
      insulin and IGFBP-1 concentrations; and 3) a blunted decrease in serum IGFBP-1
      during an OGTT.

PMID- 7521341
TI  - 1,25-Dihydroxyvitamin D3 increases secretion of insulin-like growth factor
      binding protein-4 (IGFBP-4) by human osteoblast-like cells in vitro and elevates
      IGFBP-4 serum levels in vivo.
AB  - Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) are thought
      to play an important role in the regulation of bone metabolism. In the present
      study, we investigated the effect of 1,25-dihydroxyvitamin D(3) [1,25-(OH)2D3] on
      the expression and secretion of IGFBPs in human osteoblast-like osteosarcoma
      cells (MG63) and untransformed human bone-derived cells in vitro. Northern blot
      analysis revealed that 1,25-(OH)2D3 (10(-8) mol/L) increased IGFBP-4 messenger
      RNA maximally 11-fold over control level in MG63 cells (after 24 h treatment) and
      2.8-fold in human bone-derived cells (at 10(-10) mol/L). 1,25-(OH)2D3 increased
      secretion of IGFBP-4 2- and 3-fold, respectively, in MG63 cells and in human bone
      derived cells. In normal human bone-derived cells, 1,25-(OH)2D3 also stimulated
      messenger RNA expression (3.9-fold) and the secretion of IGFBP-3 (2.2-fold). 1,25
      (OH)2D3 also increased IGFBP-4 expression in skin fibroblasts but not in
      hepatocellular carcinoma cells. Consistent with these in vitro findings,
      treatment of human subjects with high doses of oral 1,25-(OH)2D3 (2-3
      micrograms/day) for psoriasis resulted in a significant increase in serum IGFBP-4
      concentration compared with pretreatment levels. Our observations present direct
      evidence that 1,25-(OH)2D3 plays an important role in the regulation of IGFBP
      secretion in vitro and in vivo.

PMID- 7521342
TI  - Benign prostatic hyperplasia and normal prostate aging: differences in types I
      and II 5 alpha-reductase and steroid hormone receptor messenger ribonucleic acid
      (mRNA) levels, but not in insulin-like growth factor mRNA levels.
AB  - Benign prostatic hyperplasia (BPH) is so common in elderly men that the
      development of adenomatous nodules in this organ can be seen as a normal age
      dependent process. In this work, we used Northern blotting to compare the levels
      of androgen, estrogen, and insulin-like growth factor-I (IGF-I) receptor in young
      (age range, 23-33; n = 3), old normal (age range, 52-80; n = 3), and BPH-affected
      subjects (age range, 66-87; n = 15). We have also investigated in these groups
      the expression of genes coding for the two 5 alpha-reductases (types I and II),
      aromatase, IGF-I, and IGF-II. Our results show significantly increased levels of
      IGF mRNA in old healthy and BPH-affected subjects; the respective rises for IGF
      I, IGF-II, and IGF-I receptor mRNAs were 3.0-, 2.9-, and 1.5-fold (BPH) and 2.7-,
      2.4-, and 1.8-fold (old normal controls). For estrogen receptor, androgen
      receptor, and type I and II 5 alpha-reductase mRNAs, a marked but opposite effect
      was observed in adenomatous tissues only; the respective levels were 2.2-, 1.8-,
      3.9-, and 1.7-fold lower than those in young adult subjects, whereas no
      significant differences were recorded between the two normal groups. Morphometric
      analysis of each tissue specimen confirmed the significantly lower
      epithelium/stroma ratio in adenomas compared to young or old healthy tissues.
      Together, these observations suggest that prostatic adenomas may result from at
      least two conjugate processes: one characterized by a drop in the mRNA levels of
      steroid hormone receptors, which might be associated with a lower
      epithelium/stroma ratio, and another characterized by normal aging phenomena, of
      which the increased production of IGFs and IGF-I receptor transcripts could be
      biochemical markers.

PMID- 7521343
TI  - Characteristics of human follicular fluid associated with successful conception
      after in vitro fertilization.
AB  - In 23 follicular fluids (FF) each yielding an oocyte known to result in a
      clinical pregnancy after in vitro fertilization, the following substances were
      measured: free and total concentrations of estradiol (E2), progesterone (P4),
      testosterone (T), androstenedione (A), immunoreactive inhibin, insulin-like
      growth factor-binding protein-1, alpha 1-antitrypsin, and placenta protein-14. In
      addition, FF volume and follicular diameter at the time of oocyte recovery were
      recorded. The characteristics of these pregnancy-associated follicles were
      compared with those of FF obtained from women who failed to conceive after embryo
      transfer. The FF were collected from 14 women who became pregnant and 14 women
      who did not conceive. The ultrashort GnRH agonist protocol was used for ovarian
      stimulation. Pregnancy was associated with follicles showing a significantly
      higher E2/T ratio than follicles in which the oocyte failed to implant or did not
      cleave in vitro (P < 0.01). In addition, FF volume and follicular diameter were
      significantly higher in pregnancy-associated follicles than in follicles in which
      the oocyte failed to implant or did not cleave in vitro (P < 0.05). The E2/A
      ratio was higher in pregnancy-associated follicles than in follicles in which the
      oocyte failed to implant, but the difference did not reach significance (0.05 < P
      < 0.1). No difference was found when pregnancy-associated follicles and follicles
      not associated with pregnancy were compared with respect to the levels of free
      and total E2, P4, T, A, immunoreactive inhibin, insulin-like growth factor
      binding protein-1, alpha 1-antitrypsin, placental protein-14, and the E2/P4
      ratio. This study demonstrates a correlation between the pregnancy potential of
      oocytes and the ratio of E2 to androgens in FF. It confirms and extends the
      correlation between the E2/androgen ratio and follicular health and maturity. A
      low E2/androgen ratio seems to express early follicular atresia, which affects
      the viability of the enclosed oocyte negatively and limits the chances of a
      resulting preembryo to implant and establish itself as a pregnancy.

PMID- 7521344
TI  - Regulation of insulin-like growth factor (IGF) binding protein-5 in the T47D
      human breast carcinoma cell line by IGF-I and retinoic acid.
AB  - The T47D human breast carcinoma cell line has been shown to synthesize insulin
      like growth factor-I (IGF-I) binding proteins (IGFBPs) and IGF-I receptors, and
      to exhibit a mitogenic response to exogenous IGF-I. We have used T47D cells to
      investigate the regulation of IGFBPs by IGF-I and retinoic acid (RA), agents that
      affect cell proliferation and have been shown to regulate IGFBP levels in other
      cell types. Exposure of T47D cells to IGF-I resulted in the appearance of IGFBP
      2, -4, and -5 in conditioned medium but had no effect on the levels of IGFBPs in
      Triton X-100-extracted cells. This effect was most pronounced for IGFBP-5 and was
      also elicited by an IGF-I analog that retains affinity for IGFBPs but not by
      insulin or IGF analogs that have decreased affinity for IGFBPs. Additionally,
      this effect was not associated with a change in IGFBP-5 messenger RNA (mRNA)
      levels; however, the appearance of IGFBP-5 in the conditioned medium was
      inhibited by an anti-IGF-I receptor antibody (alpha IR-3). RA decreased IGFBP-5
      mRNA levels and cell-associated IGFBP-5 in both the presence and absence of IGF-I
      and inhibited the IGF-I-stimulated secretion of IGFBP-5 into T47D cell
      conditioned medium. These results suggest that IGF-I increases IGFBP-5 levels in
      the T47D cell line both through direct interaction with IGFBP-5 as well as
      through a receptor-mediated process that does not require direct interaction with
      IGFBPs. The latter results are consistent with an effect of IGF-I on a factor
      that may modulate an IGFBP protease activity. The inhibitory effect of RA, on the
      other hand, appears to be due primarily to regulation of IGFBP-5 mRNA levels.
      Thus, IGFBP-5 accumulation appears to be positively regulated by IGF-I,
      potentially at the level of susceptibility to proteolysis, and negatively
      regulated at the level of gene expression by RA.

PMID- 7521345
TI  - Secretion of platelet-activating factor acetylhydrolase by human decidual
      macrophages.
AB  - Platelet-activating factor (PAF) metabolism in the maternal-fetal decidual
      interface has been investigated. Human decidua was obtained from patients at term
      and not in labor after cesarean section. The cells were isolated by enzymic
      digestion, followed by Ficoll-Paque centrifugation, or were purified further by
      discontinuous Percoll density gradient centrifugation. Cell populations were
      analyzed by flow cytometry after labeling with macrophage-specific antibodies.
      Twenty-seven percent of the cells obtained after enzymic digestion and Ficoll
      Paque density gradient centrifugation had macrophage surface markers. The
      decidual cell population secreted PAF-acetylhydrolase (PAF-AH) activity. The
      secreted PAF-AH was the plasma-type isozyme. Synthesis and secretion was
      inhibited by actinomycin-D or cycloheximide. The PAF-AH activity secreted into
      the culture medium correlated positively with the number of macrophages. Flow
      cytometric purification yielded a 96% macrophage marker-positive population. The
      macrophages were shown to be the only cell types of decidual tissue that secreted
      PAF-AH. Treatment with anti-CD14 monoclonal antibody and complement specifically
      blocked PAF-AH secretion by collagenase-dispersed cells. It is concluded that
      decidual macrophages produce and secrete PAF-AH of the plasma type, and it is
      suggested that these cells may play an important role in PAF metabolism during
      parturition.

PMID- 7521346
TI  - Use of insulin-like growth factor-binding protein-2 (IGFBP-2), IGFBP-3, and IGF-I
      for assessing growth hormone status in short children.
AB  - Insulin-like growth factor-binding protein-2 and -3 (IGFBP-2 and -3) are members
      of a family of proteins that are present in extracellular fluids and bind IGF-I
      and -II. IGFBP-2 is regulated differently from IGF-I and IGFBP-3, because its
      serum concentrations are elevated in some adults with GH deficiency (GHD),
      whereas IGF-I and IGFBP-3 concentrations are usually decreased. The purposes of
      this study were to define the normal range of IGFBP-2 concentrations in children,
      to determine its efficacy in the diagnosis of GHD, and to compare the diagnostic
      value of measurements of the serum GH response to provocative testing with
      results of measurements of IGFBP-2, IGFBP-3, and IGF-I. Mean serum IGFBP-2
      concentrations ranged from 263 +/- 101 ng/mL (mean +/- SD) during infancy to 136
      +/- 38 ng/mL in normal 15- to 18-yr-olds (P < 0.001), whereas IGFBP-3 increased
      from 1211 +/- 384 to 2781 +/- 382 ng/mL in the same age groups. Thirty-nine of 49
      children with GHD and low IGF-I values (serum GH response, < or = 1 ng/mL after 2
      provocative tests) had serum IGFBP-2 concentrations that were greater than 2 SD
      above their corresponding age-adjusted means. In contrast all 49 of these
      children had IGFBP-3 values that were below normal for age. Because serum IGFBP-2
      concentrations are regulated by GH directly and not through IGF-I, the IGFBP-2 to
      IGF-I ratio was used to determine whether it improved diagnostic accuracy. Fifty
      of 57 GH-deficient children had IGFBP-2/IGF-I ratios that were greater than 2 SD
      above the mean. This included 48 of 49 children with low IGF-I and 2 of 8
      children with normal IGF-I. Fifty-three of the 57 children with GHD had decreased
      IGFBP-3 values. Among 23 children with idiopathic short stature (ISS) who had
      normal responses to GH stimulation testing (serum GH, > 10 ng/mL), 7 had low IGF
      I values. Of the 7, all had an increased IGFBP-2/IGF-I ratio and a low IGFBP-3
      level. Of the remaining 16 children with normal IGF-I, 13 had a normal IGFBP
      2/IGF-I ratio and normal IGFBP-3 values. Three had low IGFBP-3 and an increased
      IGFBP-2/IGF-I ratio. In 76% of the 80 short-statured patients studied, there was
      concordance among serum GH responses to provocative tests, IGF-I, IGFBP-2/IGF-I
      ratio, and IGFBP-3.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7521347
TI  - Treatment of methimazole-induced agranulocytosis using recombinant human
      granulocyte colony-stimulating factor (rhG-CSF).
AB  - Agranulocytosis, although extremely infrequent, is a serious complication of
      antithyroidal drug therapy in patients with hyperthyroidism. Presently, there is
      no specific therapy for this life-threatening complication, and recovery time is
      highly variable. Recently, recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) was reported to be effective in shortening the recovery time of
      the neutropenia in patients undergoing chemotherapy. The present study was
      undertaken to determine the efficacy of rhG-CSF administration in patients with
      methimazole-induced (MMI) agranulocytosis. Thirty-four patients (7 males and 27
      females, ages 16-68 yr) with MMI agranulocytosis were divided into 3 groups:
      group A (n = 11) was treated with antibiotics only; group B (n = 11) received
      antibiotics and dexamethasone, 8 mg/day; and group C (n = 12) was treated with
      antibiotics and im injections of rhG-CSF, 75 micrograms/day. Patients in groups A
      and B were studied retrospectively. When rhG-CSF became available, patients in
      group C were studied prospectively. Bone marrow sternal punctures were performed
      in all group C patients who were then divided into 2 subgroups according to the
      granulocyte to erythrocyte count ratio (G:E). Group C1 (n = 6) had a G:E ratio of
      less than 0.5, and group C2 (n = 6) had a ratio of more than or equal to 0.5.
      Recovery time in all groups was defined as the number of days required for the
      peripheral granulocyte count to be greater than 1.0 x 10(9)/L. There was no
      significant difference in recovery time between groups A and B: 10.1 +/- 2.2 and
      12.3 +/- 1.9 days (mean +/- SE), respectively. P was not significant; the
      administration of dexamethasone proved to be ineffective in shortening the time
      for recovery from peripheral granulocytes. On the other hand, recovery time was
      significantly shorter in group C (6.8 +/- 1.2 days mean +/- SE) compared with
      groups A and B (P < 0.05). Group C2 recovered in 2.2 +/- 0.6 days whereas group
      C1 took much longer, 9.8 +/- 1.3 days (P < 0.001). There was a direct correlation
      between the G:E ratio and the peripheral leucocyte count, r = 0.806, P < 0.01.
      Furthermore, rhG-CSF significantly shortened recovery time when the peripheral
      granulocyte count was greater than 0.1 x 10(9)/L (group C2) compared with
      patients whose counts were less than 0.1 x 10(9)/L (group C1), 2.2 +/- 0.4 vs.
      8.6 +/- 1.3 days, respectively (P < 0.001). These data indicate that
      administration of steroids is ineffective in shortening the duration of recovery
      in patients with MMI agranulocytosis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7521349
TI  - PRISMATIC case: bienvenidos a mi tierra de soledad: from poetry to molecular
      biology in southern Ecuador.

PMID- 7521348
TI  - Effect of human galanin on growth hormone prolactin, and antidiuretic hormone
      secretion in normal men.
AB  - Galanin is a brain-gut peptide occurring widely in the central and peripheral
      nervous system. Effects of iv administration of synthetic human galanin on
      pituitary GH, PRL, and antidiuretic hormone secretion were studied. Intravenous
      infusion of the peptide resulted in a significant increase in plasma GH levels
      whereas PRL and antidiuretic hormone did not significantly change. These findings
      suggest that galanin might play a role in modulating GH secretion in humans.

PMID- 7521350
TI  - Expression of three somatostatin receptor subtypes in pituitary adenomas:
      evidence for preferential SSTR5 expression in the mammosomatotroph lineage.
AB  - The expression of three somatostatin receptor subtypes, SSTR3, SSTR4, and SSTR5,
      was evaluated in 33 pituitary tumor specimens. SSTR3 expression was studied by
      reverse transcription coupled to polymerase chain reaction, whereas SSTR4 and
      SSTR5 expression was determined by ribonuclease protection assay. SSTR3 was
      expressed in 6 of 7 GH-secreting tumors, all 8 clinically nonfunctioning tumors,
      all 3 prolactinomas, and 1 of 2 ACTH-secreting tumors tested. Eight
      nonfunctioning adenomas had undetectable messenger ribonucleic acid levels of
      SSTR4, and only 1 of them expressed SSTR5. SSTR4 expression was also undetectable
      in 11 GH-secreting tumors, 3 prolactinomas, and 1 ACTH-secreting tumor tested. In
      contrast, SSTR5 was highly expressed in 10 of 11 GH-secreting adenomas and 1
      prolactinoma. Two prolactinomas and 1 ACTH-secreting tumor had low levels of
      expression of SSTR5. The widespread pituitary adenoma expression of SSTR3,
      regardless of hormonal secretory type, suggests that SSTR3 might be involved in a
      somatostatin action(s) other than GH or TSH regulation. SSTR5 is expressed
      predominantly in mammosomatotroph-derived tumors, suggesting that this receptor
      subtype may be an important determinant of GH secretion in acromegaly.

PMID- 7521351
TI  - Calcium-dependent protein kinase-C activity in human adrenocortical neoplasms,
      hyperplastic adrenals, and normal adrenocortical tissue.
AB  - The calcium- and phospholipid-dependent protein kinase-C (PKC) is a critical
      enzyme of cellular signal transduction. In this report we studied calcium
      dependent total PKC activity in eight adrenocortical carcinomas (group 1), nine
      adrenocortical adenomas (group 2), six hyperplasias (group 3), and five human
      normal adrenal tissues (group 4). The PKC activity assay was based on
      phosphorylation of a specific synthetic peptide from myelin basic protein. The
      specificity of the assay was confirmed by using an inhibitor peptide common to
      alpha-, beta-, and gamma-isoenzymes of PKC. The median value in group 1 was 1.15
      pmol 32P/min.micrograms protein (range, 0.55-2.19), that in group 2 was 1.2
      (range, 0.74-2.7), that in group 3 was 0.915 (range, 0.6-1.7), and that in group
      4 was 1.22 (range, 0.6-3.95). The calcium-dependent total PKC activity was
      similar in the four groups studied. We did not find any correlation between
      urinary total cortisol, serum cortisol, testosterone, dehydroepiandrosterone,
      dehydroepiandrosterone sulfate, androstenedione, aldosterone, and estradiol
      concentrations and PKC activity. These findings suggest that the calcium
      dependent PKC activity is not elevated in adrenocortical tumors and is not a
      useful marker of adrenocortical malignancy.

PMID- 7521352
TI  - Human chorionic gonadotropin beta-subunit nicking enzymes in pregnancy and cancer
      patient serum.
AB  - hCG is a dimer composed of an alpha- and a beta-subunit, joined noncovalently. In
      addition to the hCG dimer, uncombined alpha- and beta-subunits (free beta) and
      nicked hCG and free beta molecules (cleaved at 44-45 or 47-48) can be detected in
      the circulation. Of these circulating molecules, only the intact hCG dimer fully
      expresses biological activity. The pathways that dissociate, nick, and degrade
      hCG and beta-subunit molecules in pregnancy are unknown and could have a major
      role in regulating hormone levels. Immunoassays for intact (nonnicked) hCG and
      intact (beta-subunit (with < 1% detection of nicked molecules) and a subtractive
      immunoassay system for measuring nicked hCG levels have been described
      previously. A multiantibody scavenger assay is described here for measuring
      nicked beta-subunit levels (< 6% detection of intact beta-subunit). In this
      report we use these four assays to assess conversion of intact hCG or beta
      subunit to nicked forms over time (nicking enzyme activities) in control (healthy
      nonpregnant), pregnant, and cancer patient serum samples. Pools of pregnancy and
      control sera were supplemented with intact hCG and its dissociated beta-subunit
      and incubated at 37 C. Intact and nicked molecule measurements were made between
      0-48 h. In two different pools of control sera, no loss of intact hCG or intact
      beta-subunit and no significant gain in nicked hCG or nicked beta-subunit were
      detected over 48 h. This indicated a lack of nicking enzyme activity in control
      serum. In two different pools of first trimester pregnancy sera, we found no
      obvious loss of intact hCG or gain of nicked hCG levels over 48 h. However, we
      found 70% and 62% losses (pools 1 and 2) of intact beta-subunit and 51% and 39%
      gains of nicked beta-subunit over the same time period. We inferred that an
      uncombined or free beta-subunit-modifying activity was present in pregnancy
      serum. We repeated the pregnancy serum experiment with six different
      concentrations of beta-subunit (0.62-29 mg/L). A linear relationship, percent
      nicking against time, existed for the six concentrations for up to 6 h at 37 C (r
      = 0.97); after that, the rate of nicking declined. A plot of rate against
      concentration against revealed a classical Michaelis-Menten enzyme relationship
      (logarithmic regression, r = 0.96). The pregnancy serum beta-subunit nicking
      activity was partially purified by gel filtration. A single peak of activity
      emerged, eluting between the 150,000-443,000 mol wt standards.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 7521354
TI  - Effect of insulin on the hepatic production of insulin-like growth factor-binding
      protein-1 (IGFBP-1), IGFBP-3, and IGF-I in insulin-dependent diabetes.
AB  - Insulin-like growth factors (IGFs) circulate attached to binding proteins
      (IGFBPs). Only the unbound form of IGF is suggested to be biological active. The
      main source of circulating IGF-I and IGFBP-1 is considered to be the liver, but
      that of circulating IGFBP-3 is not known. IGF-I and IGFBP-3 are GH dependent,
      whereas IGFBP-1 is insulin regulated. The aim of the present study was to examine
      the effect of insulin on the hepatic secretion of IGFBP-1, IGFBP-3, and IGF-I.
      Seven insulin-dependent diabetic patients in whom insulin was withheld for 12 h
      were studied in the overnight fasted state. Blood was sampled simultaneously from
      the hepatic vein, a peripheral vein, and an artery before and during insulin
      infusion for 3 h. The basal IGFBP-1 levels in the peripheral vein were several
      fold elevated (249 +/- 44 micrograms/L) compared to those in healthy subjects (37
      +/- 2 micrograms/L). Fasting IGFBP-1 concentrations were inversely correlated to
      the insulin levels (r = -0.918; P < 0.001). The mean IGF-I concentration (175 +/-
      17 micrograms/L; -1.62 +/- 0.38 SD score) was decreased compared with that in age
      matched healthy subjects. The basal IGFBP-3 levels in the peripheral vein (4.50
      +/- 0.33 mg/L) were within the normal range. There was a significant correlation
      in the hepatic vein between fasting IGF-I and IGFBP-3 levels (r = 0.928; P <
      0.001). Basal splanchnic IGFBP-1 production was 18 +/- 7 micrograms/min, whereas
      no basal net exchanges of IGF-I or IGFBP-3 were observed across the splanchnic
      area. Insulin inhibited splanchnic IGFBP-1 production within 120 min and glucose
      output within 20 min. Serum IGF-I, but not IGFBP-3, concentrations increased
      significantly during the insulin infusion. In summary, this study demonstrates
      the existence of considerable IGFBP-1 production from the liver during
      insulinopenia and the complete blocking of splanchnic IGFBP-1 production and
      increases in serum levels of IGF-I by insulin despite no effect on IGFBP-3
      levels. Thus, insulin may play a role in determining the bioavailability of IGF
      I.

PMID- 7521353
TI  - The midcycle gonadotropin surge in normal women occurs in the face of an
      unchanging gonadotropin-releasing hormone pulse frequency.
AB  - The midcycle gonadotropin surge is a critical event in normal reproductive cycles
      and requires functional integration of the hypothalamus, pituitary, and ovary. To
      determine whether a change in GnRH frequency occurs coincident with the onset or
      termination of the surge in normal women, 20 studies were performed at a sampling
      interval of every 5 min for up to 36 h. The frequency of pulsatile GnRH secretion
      was assessed by the use of two surrogate markers of its secretion, LH and free
      alpha-subunit (FAS). The timing of the studies was prospectively determined by
      serial ultrasound and previous cycle history, whereas measurements of LH, FSH,
      estradiol, and progesterone in daily blood samples were used retrospectively to
      locate the frequent sampling study in relation to the day of ovulation in each
      individual. The frequent sampling studies were divided into late follicular phase
      (LFP; days -4 to -2) and early, mid-, and late portions of the midcycle surge
      (days -1 to 1) in relation to the 95% confidence limits of the LH peak derived
      from daily samples in 69 normal ovulatory women. The patterns of LH and FAS
      secretion were pulsatile at all times during the midcycle surge. The amplitude of
      LH pulsations increased from the LFP and early surge to the midportion of the
      midcycle surge (5.9 +/- 6 and 15.1 +/- 5 vs. 39.0 +/- 3 IU/L; P < 0.0001) and
      decreased from the mid- to the late portion of the surge (13.4 +/- 5 IU/L; P <
      0.0001). Likewise, the amplitude of FAS pulse increased from the LFP and early
      surge to the midportion of the surge (82.4 +/- 59 and 153.1 +/- 50 vs. 421.4 +/-
      35 ng/L; P < 0.0001) and decreased from the mid- to the late portion of the surge
      (190.8 +/- 49 ng/L; P < 0.0002). Although there was excellent concordance of
      pulsatile secretion of LH and FAS, significantly more pulses of FAS were detected
      than of LH (P < 0.0001). There was no change in frequency (expressed as
      interpulse interval) between the LFP and the early and midportions of the surge
      for LH (70.0 +/- 8, 67.5 +/- 7, and 65 +/- 5 min, respectively) or FAS (55.1 +/-
      7, 54.6 +/- 6, and 60.0 +/- 4 min). However, there was an increase in LH
      interpulse interval (decrease in pulse frequency) in the late portion of the
      surge (87.0 +/- 6 min) compared to the early and midportions of the surge (P <
      0.02 and P < 0.0005, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7521355
TI  - Enzyme immunoassay with enhanced specificity for detection of antibodies to
      Chlamydia trachomatis.
AB  - Two different methods for preventing the binding of cross-reacting antibodies to
      the genus-reactive chlamydial lipopolysaccharide (LPS) were used to improve the
      specificity of an enzyme immunoassay for the determination of antibodies to
      Chlamydia trachomatis. Coated elementary bodies were treated with either sodium
      periodate, to oxidize the antigenic sites of the LPS, or Triton X-100, to extract
      the LPS. By using these new enzyme immunoassays, the standard enzyme immunoassay,
      and the whole inclusion fluorescence (WIF) assay, antibodies to C. trachomatis
      were determined in sera from different groups of patients and controls. Paired
      serum samples from patients with culture-proven urogenital C. trachomatis
      infections showed similar responses in all three assays. Paired serum samples
      from patients with Chlamydia psittaci infections showed similar responses in the
      WIF assay and the standard enzyme immunoassay, whereas significantly reduced
      titers were obtained in the enzyme immunoassays with treated antigen, especially
      in the convalescent-phase serum samples. Serum samples from patients with
      symptoms suggestive of infection with C. trachomatis, pregnant women, and blood
      donors were evaluated by all three types of assays. Eighty percent of the
      significant reductions in immunoglobulin G (IgG), IgA, and IgM titers were
      observed in sera with WIF assay titers in the lower classes (IgG, 1: < or = 256;
      IgA, 1: < or = 32; IgM, 1: < or = 16). From these results we conclude that
      oxidation of the antigen by sodium periodate is a simple and effective method of
      producing an enzyme immunoassay with enhanced specificity that could be useful
      for diagnostic purposes and seroepidemiological studies.

PMID- 7521356
TI  - Screening of respiratory tract specimens for the presence of Mycobacterium
      tuberculosis by using the Gen-Probe Amplified Mycobacterium Tuberculosis Direct
      Test.
AB  - A prospective 2-month trial involving 617 respiratory tract specimens was
      conducted to compare sensitivity, specificity, and predictive values of the newly
      developed Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test kit (AMTDT;
      Gen-Probe, Inc., San Diego, Calif.) for the rapid detection of Mycobacterium
      tuberculosis and of fluorescent acid-fast staining versus combined BACTEC 12B and
      solid-medium cultures as the "gold standard." A total of 590 specimens were
      culture and AMTDT negative. Twenty-one (3.4%) cultures yielded M. tuberculosis.
      Of these, 15 (71.4%) were detected by AMTDT, whereas 6 (28.6%) were missed. M.
      tuberculosis did not grow in six (28.6%) of AMTDT-positive specimens derived from
      three patients under treatment for tuberculosis. AMTDT exhibited a sensitivity, a
      specificity, a negative predictive value, and a positive predictive value of
      71.4, 99, 99, and 71.4%, respectively. In comparison, the same values for
      fluorescent microscopy were 66.7, 98.3, 98.8, and 58.3%, respectively. AMTDT was
      easy to perform and highly specific. However, a screening test would require an
      improved sensitivity and, when feasible, the implementation of an internal
      amplification control.

PMID- 7521359
TI  - Usefulness of gram staining of blood collected from total parenteral nutrition
      catheter for rapid diagnosis of catheter-related sepsis.
AB  - The accuracy of Gram staining of blood drawn from catheters used to administer
      total parenteral nutrition was compared with paired quantitative blood cultures
      for the diagnosis of catheter-related sepsis. Gram staining was positive in 11 of
      18 episodes of catheter-related sepsis documented by quantitative culture
      (sensitivity, 61%) but in none of the 5 episodes of fever unrelated to catheter
      infection. Thus, this procedure enabled the rapid presumptive diagnosis and
      guidance of antimicrobial therapy for total parenteral nutrition catheter sepsis,
      with a positive predictive value of 100% and a negative predictive value of 42%.

PMID- 7521357
TI  - Detection of Bartonella (Rochalimaea) quintana by routine acridine orange
      staining of broth blood cultures.
AB  - Bartonella quintana was isolated from 34 BACTEC nonradiometric aerobic resin
      blood cultures for 10 adults. Nine patients were initially diagnosed by routine
      acridine orange staining of routine cultures that had been incubated for 8 days.
      All subcultures grew on chocolate agar within 3 to 12 days (median, 6 days). The
      PLUS 26 high-volume aerobic resin medium, combined with acridine orange stain and
      subculture, is an effective system for detection and isolation of B. quintana
      from blood.

PMID- 7521358
TI  - Direct and rapid detection of Erysipelothrix rhusiopathiae DNA in animals by PCR.
AB  - Erysipelothrix rhusiopathiae is a gram-positive rod capable of causing erysipelas
      in swine. To establish a method for specifically detecting E. rhusiopathiae for
      practical applications, such as for the inspection of slaughterhouses, the
      feasibility of using primers derived from the DNA sequence coding for 16S rRNA in
      a PCR-specific detection system was investigated. Oligonucleotide primers were
      designed to amplify a 407-bp DNA fragment by PCR. The amplification was specific
      to the Erysipelothrix DNA but not to that of other bacterial genera tested. This
      PCR-based method efficiently and specifically detected the Erysipelothrix DNA
      sequence in joint and spleen samples from mice within 6 h, and application of the
      407-bp DNA segment from samples containing very low numbers of bacteria (< 20
      bacteria per spleen from mice) was possible. Although this PCR amplification is
      specific for the Erysipelothrix genus, which contains at least two species, E.
      rhusiopathiae and E. tonsillarum, it can be concluded that all Erysipelothrix
      strains detected by this PCR system in diseased pigs are E. rhusiopathiae because
      only E. rhusiopathiae is virulent for pigs. These results show that this PCR
      amplification system using the DNA sequence coding for 16S rRNA is very rapid and
      reliable and avoids cumbersome and lengthy cultivation steps, demonstrating that
      this system could be used for practical applications.

PMID- 7521360
TI  - The interaction of immunosuppressive compounds in tandem stimulated peripheral
      human lymphocytes.
AB  - We have developed an in vitro system to model the interactions of drugs used to
      treat transplant rejection. This system consists of stimulation of human
      lymphocytes with a primary mitogen (anti-T-cell receptor complex antibodies (OKT3
      or wt31)) and treatment with a primary immunosuppressive drug (ISD) (Cyclosporine
      A (CsA) or FK-506)). This is later followed by stimulation with a secondary
      mitogen (Interleukin-2 or anti-CD28), and treatment with a second ISD. This
      system allows a variety of concentrations and compounds to be rapidly tested. We
      have used this system to study the effect of various compounds when used as
      either primary or secondary ISDs. Our results show that when CsA is used as the
      primary ISD, further proliferation can be inhibited by rapamycin, mycophenolic
      acid, or suramin. When FK-506 is the primary ISD, inhibition of proliferation by
      rapamycin is variable depending on the primary and secondary mitogens. If
      rapamycin is the primary ISD, both CsA and FK-506 show antagonistic interactions.
      These results suggest that the order in which combinations of ISDs are
      administered in transplantation may have significant effects on the clinical
      outcome.

PMID- 7521361
TI  - CD59 costimulation of T cell activation. CD58 dependence and requirement for
      glycosylation.
AB  - In addition to the TCR-CD3 complex, T lymphocytes can be activated via another
      surface glycoprotein, the CD2 molecule. CD58 is the principal ligand for human
      CD2; CD59 and CD48 are two additional, low affinity ligands that have been
      defined for CD2. In this study, we have explored the role of CD59 in T cell
      activation. We have expressed human rCD58 and rCD59 molecules in Chinese hamster
      oocytes (CHO), and tested paraformaldehyde-treated transfectants for the ability
      to promote proliferation of and IL-2 secretion from PBMC and human purified T
      cells. We have shown that CD59 enhanced CD58-dependent T cell proliferation and
      IL-2 secretion in the presence of suboptimal concentration of PHA or a
      submitogenic combination of stimulatory anti-CD2 mAbs, presence of suboptimal
      concentration of PHA or a submitogenic combination of stimulatory anti-CD2 mAbs,
      T11-2 + T11-3. CD59-dependent costimulation was dependent on several factors
      including the level of co-expression of CD58, the ratio of CHO cell transfectants
      to T cells added in culture, the concentration of mitogen, and also donor
      dependent differences. As expected, CD59 costimulation of CD58-dependent T cell
      proliferation was inhibited by Abs directed against CD59, CD58, and CD2. In our
      hands, the CD59 molecule itself, in the absence of CD58, was unable to support
      proliferation alone even in the presence of exogenous recombinant IL-1, IL-2, or
      IL-6. Finally, the ability of CD59 to enhance CD58-dependent T cell responses was
      shown to be dependent on N-glycosylation of CD59 at amino acid Asn18.

PMID- 7521363
TI  - Costimulation of human CD4+ T lymphocytes with B7 and lymphocyte function
      associated antigen-3 results in distinct cell activation profiles.
AB  - This study describes the distinct roles of B7 and LFA-3 in the regulation of T
      cell responses. Activation of CD4+ T cells with Chinese hamster ovary (CHO)
      DR4/B7 and CHO-DR4/LFA-3 cells that present the superantigen staphylococcal
      enterotoxin A resulted in significant T cell proliferation and substantial
      production of TNF and IFN-gamma. Strong IL-2 production was recorded in B7
      costimulated, but not LFA-3-costimulated, cultures. The presence of B7 induced a
      more vigorous and prolonged proliferative T cell response compared with LFA-3
      costimulation. In contrast, LFA-3 was more efficient than B7 in mediating cell
      adhesion of CD4+ T cells. Costimulation with the CHO-DR4/B7/LFA-3 triple
      transfectant resulted in enhanced cell adhesion, proliferation, and cytokine
      production compared with either DR4/B7 or DR4/LFA-3 alone. Optimal production of
      IL-2 by naive and memory CD4+ T cells was seen only when cells were costimulated
      with B7, whereas IFN-gamma production was induced in memory cells by both LFA-3
      and B7. The Jurkat T cell line responded to CHO-DR4/B7/LFA-3 in a manner similar
      to peripheral blood CD4+ T cells. Reverse transcriptase-PCR analysis of Jurkat
      cells stimulated with staphylococcal enterotoxin E and the different CHO
      transfectants revealed that the cooperative effect of B7 and LFA-3 on IL-2
      production was also seen at the mRNA level. The large amounts of IL-2 produced by
      B7 costimulation indicate a paracrine function of the B7/CD28 pathway, whereas
      the LFA-3/CD2 pathway provides strong adhesion and may facilitate autocrine T
      cell expansion. Combined expression of the B7 and LFA-3 molecules seems to
      provide an optimal Ag-presenting function that ensures strong adhesion and
      optimal signal transduction.

PMID- 7521362
TI  - Resistance of CTL to perforin-mediated lysis. Evidence for a lymphocyte membrane
      protein interacting with perforin.
AB  - Cytotoxic T lymphocytes are highly resistant to killing by their own cytolytic
      protein perforin. We have investigated the molecular basis of this self
      protection mechanism. CTL withstood high dosages of perforin, when complete lysis
      was obtained with various tumor target cell lines. A peptide-specific CTL clone
      readily lysed tumor targets presenting the peptide, but was unable to kill the
      peptide-presenting CTL in spite of equal degranulation. With streptolysin O, a
      pore-forming lytic protein of bacterial origin, no difference in susceptibility
      between the various targets was detected. Perforin was radioactively labeled by
      using the Bolton and Hunter method without any loss of its lytic activity.
      Experiments performed at 4 degrees C revealed that, on all of the cells studied,
      binding of the labeled perforin to the membrane is reversible and strictly Ca(2+)
      dependent. After a short exposure to 37 degrees C, perforin was no longer
      dissociated from cell membranes by EDTA. Although no correlation between
      susceptibility and the extent of perforin binding was detected, differences in
      the conformation of membrane-bound perforin were observed. Perforin adsorbed to
      resistant cells was cleaved by trypsin into a 55-kDa (C-terminal) and a 10- to 15
      kDa (N-terminal) fragment, whereas this cleavage was not found on tumor cell
      bound perforin. A portion of perforin was included in the Triton X-114 detergent
      phase at 4 degrees C on resistant CTLs only. Our results are compatible with the
      notion that a protective molecule, specifically expressed on CTLs, interacts with
      perforin, thereby rendering it lytically inactive.

PMID- 7521364
TI  - Involvement of LFA-1/intracellular adhesion molecule-1-dependent cell adhesion in
      CD40-mediated inhibition of human B lymphoma cell death induced by surface IgM
      crosslinking.
AB  - B cells have been shown to receive negative signals for their growth through
      crosslinking of surface IgM (sIgM), and it has been demonstrated that anti-IgM
      Abs induce B cell death. Proliferation of B cells in response to Ag stimulation
      in vivo may thus require additional signals that inhibit the sIgM-transduced
      negative signals. Signaling through CD40 has been proposed as a candidate for
      such costimulatory signals. To investigate the role of CD40-transduced signals in
      sIgM-mediated B cell death, we used a human B cell line (DND-39) that expresses
      sIgM, sIgD, and CD40. Crosslinking of sIgM, but not sIgD, by Abs induced DND-39
      cell death. The dying cells showed the morphology of apoptosis and DNA
      fragmentation. Anti-CD40 Abs induced homotypic adhesion of DND-39 cells and
      rescued them from anti-IgM Ab-induced cell death. Anti-CD40 Abs inhibited anti
      IgM Ab-induced cell death when added within 3 h after stimulation with anti-IgM
      Ab. Treatment with Abs against CD11a, CD18, or CD54 inhibited not only the
      homotypic adhesion but also the inhibition of anti-IgM Ab-induced apoptosis by
      anti-CD40 Ab. CD11a antisense decreased the surface CD11a expression, the anti
      CD40 Ab-induced homotypic adhesion, and the inhibitory effect of anti-CD40 Ab on
      anti-IgM Ab-induced apoptosis. The data show that LFA-1/ICAM-1-dependent cell
      adhesion induced by signaling through CD40 plays an important role in the
      inhibition of anti-IgM Ab-induced apoptosis of DND-39 cells.

PMID- 7521365
TI  - The role of the Fas lytic pathway in a perforin-less CTL hybridoma.
AB  - The murine CTL hybridoma PMMI has been shown by the most sensitive techniques to
      be devoid of perforin. We thus used PMMI activated with PMA and ionomycin, to
      investigate possible alternate lytic pathways in CTLs in the absence of perforin.
      We found that PMMI is equipped with membrane TNF-alpha as a potential lytic
      mechanism, but TNF-alpha is unlikely to be involved in acute (4 h) lytic
      reactions. On the other hand, PMMI readily lyses target cells expressing the gene
      for the Fas Ag, but does not lyse target cells expressing fas antisense DNA. The
      generation of fas-dependent lysis required protein synthesis in PMMI, but target
      cell protein synthesis was not required for lysis. Lysis of Fas-positive target
      cells by PMMI was accompanied by DNA fragmentation, and both lysis and DNA
      fragmentation were blocked by inhibition of protein synthesis in the effector
      cell. We find the relative extent and kinetics of fas-dependent lysis and DNA
      fragmentation indistinguishable from that seen in "classical" CTL lytic assays.
      Both fas- and perforin-dependent lysis were blocked by inhibitors of poly(ADP)
      ribosylation. We found very little difference in the sequence of events in target
      cells lysed by the fas pathway compared with the classical (probably perforin)
      lytic pathway. Given the widespread distribution of fas, particularly in
      hematopoietic target cells, caution may be required in interpreting the
      relationship between parameters such as DNA fragmentation and 51Cr-release solely
      on the basis of the granule exocytosis model.

PMID- 7521366
TI  - CD14-dependent activation of protein kinase C and mitogen-activated protein
      kinases (p42 and p44) in human monocytes treated with bacterial
      lipopolysaccharide.
AB  - To investigate mechanisms of mononuclear phagocyte cell signaling, the effects of
      bacterial LPS on protein kinase activities in normal human peripheral blood
      monocytes were examined. Incubation of intact monocytes with LPS brought about
      time- and concentration-dependent increases in myelin basic protein (MBP)
      phosphotransferase activity in high speed supernatants of cell lysates. Anion
      exchange chromatography on Mono Q demonstrated that LPS treatment resulted in two
      principal peaks of stimulated MBP kinase activity. Evidence was obtained to
      indicate that the first eluted peak of MBP kinase activity is accounted for by
      p42 and p44 mitogen-activated protein (MAP) kinases. Thus, 1) MBP kinase activity
      within peak 1 was quantitatively precipitated by anti-MAP kinase Abs, 2) the
      enzyme effectively phosphorylated a specific peptide substrate, 3) peak 1
      contained proteins of subunit size M(r) 42,000 and M(r) 44,000 that reacted
      specifically with anti-MAP kinase Abs, and that 4) were recognized by anti
      phosphotyrosine Abs only after stimulation of cells with LPS. Studies of the
      second peak of LPS-stimulated MBP kinase activity indicate that it is an isoform
      of protein kinase C (PKC) because: 1) enzyme activity was quantitatively
      immunoprecipitated by anti-PKC Abs, 2) the activity of the enzyme was potently
      and selectively inhibited by a specific peptide modeled on the autoinhibitory
      domain of PKC, and 3) the presence of a protein of subunit size M(r) 80,000
      recognized by anti-PKC Abs. Because the second peak of MBP kinase activity (like
      the first) was active in the absence of added calcium and in the presence of 2 mM
      EGTA, it appears to be a type II, calcium-independent isoform of PKC. Abs to CD14
      completely abrogated LPS-induced activation of both Mono Q peaks of MBP
      phosphotransferase activity. These results indicate that LPS coordinately
      activates both an apparently calcium-independent PKC and MAP kinase in
      mononuclear phagocytes and these responses appear to be initiated by signaling
      through the cell surface receptor, CD14.

PMID- 7521367
TI  - Endotoxin-induced early gene expression in C3H/HeJ (Lpsd) macrophages.
AB  - C3H/HeJ (Lpsd) macrophages have been shown to respond to certain LPSs, especially
      from rough mutant bacteria. C3H/OuJ (Lpsn) macrophages are induced by wild-type
      LPS, rough LPS, or lipid A to express many genes, including TNF-alpha, TNFR-2, IL
      1 beta, IP-10, D3, and D8. C3H/HeJ macrophages failed to induce any of these
      genes when cultured with wild-type LPS or synthetic lipid A, even when pretreated
      with IFN-gamma. However, rough mutant Salmonella minnesota Ra, Rc, and Rd LPS,
      and Escherichia coli D31 m3 Rd LPS induced Lpsd macrophages to express a subset
      of genes within the gene panel. Because bioactive preparations contained trace
      quantities of endotoxin protein(s), a deoxycholate-modified, phenol-water method
      was used to repurify rough LPS into an aqueous phase, and extract endotoxin
      proteins into a phenol phase. Repurified LPS failed to stimulate Lpsd
      macrophages; however, phenol fractions were approximately 10% as potent in Lpsd
      macrophages as crude rough LPS. Full potency was restored in C3H/HeJ macrophages
      when aqueous phase LPS and phenol-phase proteins were co-precipitated, suggesting
      that LPS and endotoxin proteins interact synergistically. Endotoxin proteins
      alone induced TNF-alpha, TNFR-2, and IL-1 beta, but not IP-10, D3, and D8 genes
      in both Lpsd and Lpsn macrophages. Tyrosine phosphorylation of three 41- to 47
      kDa proteins was induced by endotoxin proteins, but not by LPS, in Lpsd
      macrophages. Thus, endotoxin proteins seem to activate a signaling pathway(s)
      that converges (distal to the Lps gene product) with a subset of LPS-signaling
      pathways.

PMID- 7521368
TI  - Eosinophil granule proteins increase microvascular macromolecular transport in
      the hamster cheek pouch.
AB  - By using microscopic, fluorometric, and immunologic methods, we have assessed the
      effects of eosinophil granule proteins on the microcirculation of the hamster
      cheek pouch. The plasma clearance of FITC-dextran 150 (FITC-dx 150) was used to
      quantify macromolecular transport. Topical application of major basic protein
      (MaBP) at 0.1 and 0.5 nM increased the clearance of FITC-dx 150 from a base line
      of 591 to 1283 and 1966 nl/60 min/g, respectively. Numerous muscle fasciculations
      were also observed with the 0.5 nM dose of MaBP. Eosinophil cationic protein
      (ECP) was as potent as MaBP and caused an increase in the clearance of FITC-dx
      150, 0.5 nM eliciting 2156 nl/60 min/g. In contrast, topical application of 0.5
      nM eosinophil peroxidase (EPO) increased clearance of FITC-dx 150 to a
      significantly lower level, 1113 nl/60 min/g. Supplementing 0.5 nM EPO with 1 nM
      H2O2 enhanced the clearance of FITC-dx 150 to 2404 nl/60 min/g, suggesting
      separate cationic charge and enzymatic activity-related effects. Compared with
      these eosinophil granule proteins, eosinophil-derived neurotoxin (EDN) required a
      2000-fold higher concentration (1 microM) to elicit a significant increase in the
      clearance of FITC-dx 150 (1505 nl/60 min/g). Neither EPO, EPO+H2O2, ECP, nor EDN
      at 1 mM caused muscle fasciculations. Quantitative analysis of the suffusates
      from the preparations exposed to these eosinophil proteins did not contain
      histamine. Our results demonstrate that MaBP, ECP, EPO, and EDN increase
      microvascular transport in the hamster cheek pouch and that this increase is
      independent of endogenous histamine release. The concentrations of eosinophil
      granule proteins causing increased vascular permeability are achieved in many
      pathologic conditions suggesting that the granule proteins play an important role
      in disease.

PMID- 7521369
TI  - Activation of NF-kappa B and induction of vascular cell adhesion molecule-1 and
      intracellular adhesion molecule-1 expression in human glial cells by IL-1.
      Modulation by antioxidants.
AB  - The infiltration of leukocytes into the central nervous system is associated with
      many pathologic conditions of the brain. The mechanisms by which these immune
      cells can penetrate the blood-brain barrier and remain within the brain are not
      understood. However, elevated brain levels of the pro-inflammatory cytokine IL-1
      appear to accompany pathogenesis. The present study provides the first evidence
      that IL-1 can induce the expression of adhesion molecules for leukocytes on glial
      cells and suggests a role for the transcription factor NF-kappa B in the
      induction process. Human rIL-1 alpha was found to induce the expression of the
      cell adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1), and
      intercellular adhesion molecule-1 (ICAM-1) but not E-selectin in human 1321N1
      astrocytoma. Both VCAM-1 and ICAM-1 were detectable from 3 h and remained
      sustained for up to 72 h. Induction was inhibited by the IL-1 receptor
      antagonist. IL-1 alpha was also shown to induce the expression of VCAM-1 and ICAM
      1 in a receptor-dependent fashion in human A172 glioblastoma. Activation of the
      transcription factor NF-kappa B was also observed in 1321N1 astrocytoma in
      response to IL-1 alpha treatment and was similarly abolished by pretreatment of
      cells with antagonist. Activated NF-kappa B was apparent from 20 min and remained
      for up to 24 h. N-acetylcysteine (NAC) and pyrollidinedithiocarbamate (PDTC),
      which were shown to inhibit activation of NF-kappa B in Jurkat E6.1 lymphoblasts
      and EL4.NOB-1 thymoma, failed to block IL-1 activation of NF-kappa B in 1321N1
      astrocytoma. However, both of these antioxidants demonstrated complex modulatory
      effects on the induction of cell adhesion molecule expression by IL-1. The
      induction of VCAM-1 but not of ICAM-1 proved susceptible to inhibition by both
      PDTC and NAC. The expression of adhesion molecules for leukocytes on glial cells
      in response to IL-1 may represent an important mechanism for retention of immune
      cells in the central nervous system that may be a prologue to inflammatory
      conditions in the brain.

PMID- 7521370
TI  - Monocyte adhesion in patients with bone marrow fibrosis is required for the
      production of fibrogenic cytokines. Potential role for interleukin-1 and TGF
      beta.
AB  - Idiopathic myelofibrosis (IMF) is a hemologic disorder characterized by bone
      marrow (BM) fibrosis. The BM contains excessive deposits of extracellular matrix
      proteins and exhibits neovascularization. The fibrosis is hypothesized to be a
      reactive phenomenon secondary to a clonal myeloid disorder. Growth factors such
      as platelet-derived growth factor (PDGF), TGF-beta, and epidermal growth factor
      have been postulated as potential agents involved in BM fibrosis. We studied the
      induction of two fibrogenic cytokines, IL-1 and TGF-beta, in IMF monocytes. High
      levels of both cytokines were produced in unstimulated IMF monocytes, compared
      with background levels produced in normal controls. Most of the TGF-beta produced
      by IMF monocytes was in its active form. The spontaneous induction of IL-1 alpha,
      IL-1 beta, and TGF-beta in IMF monocytes parallels an increase in their steady
      state mRNA. Although high levels of cytoplasmic IL-1 alpha, IL-1 beta, and TGF
      beta protein were detected in monocytes that were not subjected to any form of
      adherence, the secretion of these cytokines required adhesion. High levels of
      fibronectin, hyaluronic acid, and collagen, all potential ligands for the CD44
      adhesion molecule, have been reported in the circulation of IMF patients.
      However, the Ab-binding capacity of CD44 in IMF monocytes was reduced by 50% when
      compared with normal controls. Our results indicate that monocytes and adhesion
      molecules may play a role in the induction of fibrogenic cytokines. These
      parameters may be important to the pathophysiology of BM fibrosis.

PMID- 7521371
TI  - Ichthyosis bullosa of Siemens--a disease involving keratin 2e.
AB  - Ichthyosis bullosa of Siemens (IBS) is a congenital bullous ichthyosis without
      erythroderma. In contrast to bullous congenital ichthyosiform erythroderma
      (BCIE), there is a relatively mild involvement of the skin and epidermolytic
      hyperkeratosis (EHK) is restricted to the upper suprabasal layers of the
      epidermis. Tonofilament aggregation was observed by EM in suprabasal cells from
      affected patients in the two families under study, indicative of a keratin
      abnormality. Keratin 2e is a differentiation specific type II keratin expressed
      suprabasally in the epidermis. Part of the K2e gene was amplified by polymerase
      chain reaction using genomic DNA from affected and unaffected individuals from
      two IBS families. Direct sequencing of polymerase chain reaction products
      revealed a point mutation in the highly conserved helix termination motif,
      producing the protein sequence change LLEGEE-LLEGKE. This mutation was found in
      all affected members of a five-generation kindred and also in a sporadic case in
      a second unrelated family. No mutation was seen in unaffected individuals. The
      mutation destroys a MnlI restriction site, which allowed exclusion of the
      mutation from a population of 50 unaffected unrelated individuals by restriction
      fragment analysis of K2e PCR products. This is the sixth keratin gene found to be
      involved in an inherited epidermal disorder.

PMID- 7521372
TI  - Genetic linkage of the keratin type II gene cluster with ichthyosis bullosa of
      Siemens and with autosomal dominant ichthyosis exfoliativa.
AB  - Ichthyosis bullosa of Siemens is an autosomal dominant disease characterized by
      mild hyperkeratosis and blistering. Autosomal dominant ichthyosis exfoliativa is
      a recently described disease with clinical features similar to ichthyosis bullosa
      of Siemens, but in contrast to ichthyosis bullosa of Siemens no histologic signs
      typical for epidermolytic hyperkeratosis are observed. We used linkage analysis
      to test whether keratin gene mutations might underlie both diseases. This
      analysis showed linkage of both disorders with the region of chromosome 12 in
      which the keratin type II gene cluster is located. The keratin type I gene
      cluster on chromosome 17 is excluded. These data, combined with clinical
      observations, strongly suggest that the genes coding for keratin 1 or keratin 2e,
      both expressed in the suprabasal compartment of the epidermis and located in the
      type II gene cluster, are candidate genes for ichthyosis bullosa of Siemens and
      ichthyosis exfoliativa.

PMID- 7521373
TI  - Migration of Thy-1+ dendritic epidermal cells (Thy-1+DEC): Ly48 and TNF-alpha are
      responsible for the migration of Thy-1+DEC to the epidermis.
AB  - Thy-1+ dendritic epidermal cells (Thy-1+DEC) are mainly T cells that express T
      cell receptor gamma and delta chains with limited diversity of gamma delta,
      mainly gamma 3 delta 1; such gamma 3 delta 1 TCR-bearing Thy-1+DEC originate from
      day 16 fetal thymic cells. To understand the migratory capability of Thy-1+DEC,
      we developed an in vitro model, using skin organ culture. First, emigration of
      Thy-1+DEC from the epidermis was examined. Ear skin from C3H/He mice was
      separated into two parts and incubated for 3 d with dermal side down. Thy-1+DEC
      emigrated from the epidermis into the dermis and then migrated out of the skin
      into the culture medium. Next, immigration of Thy-1+DEC into the epidermis was
      examined. Thy-1+DEC were depleted in vivo by daily application of clobetazole
      propionate solution topically onto the ears of C3H/He mice. Seven days later, ear
      skin was harvested, separated, and cultured with the dermal side up with
      syngeneic epidermal cell suspensions with a migration chamber for 3 d. It was
      found that 1) Thy-1+DEC immigrated into the Thy-1+DEC depleted epidermis as well
      as into untreated epidermis, and 2) the migratory capability of Thy-1+DEC was
      directly proved by a biolabeling technique with PKH-26. Blocking studies with
      various antibodies revealed that leukosialin (S11 monoclonal antibodies) and TNF
      alpha were important for Thy-1+DEC migration. Thus, Thy-1+DEC retain the
      potential for migration in vitro, and leukosialin and TNF alpha are partially
      responsible for the migration of Thy-1+DEC into the epidermis.

PMID- 7521374
TI  - Inducibility and expression of microvascular endothelial adhesion molecules in
      lesional, perilesional, and uninvolved skin of psoriatic patients.
AB  - Previous studies have demonstrated 1) that patterns of inducible endothelial cell
      expression of endothelial leukocyte adhesion molecule-1 (ELAM-1) and vascular
      cell adhesion molecule-1 (VCAM-1) in response to cytokines varies both with
      anatomic position within the dermal microvasculature and with the presence of
      perivascular inflammatory infiltrates, and 2) that the anatomic architecture of
      the dermal superficial plexus (SVP) is altered in inflamed lesional but not in
      univolved skin of psoriatic patients. The present study was designed to evaluate
      the pattern of cytokine inducibility of ELAM-1 and VCAM-1 in altered dermal
      microvessels of psoriatic patients. At the light microscope level, preculture
      biopsies of uninvolved and perilesional skin were indistinguishable by morphology
      and ELAM-1 and VCAM-1 expression were virtually absent. In contrast, biopsied
      lesional skin showed elongated capillary loops and increased numbers of T cells
      compared to uninvolved and perilesional skin. The dermal microvasculature of the
      SVP of lesional skin contained ELAM-1+ in 29.4% of vessels and VCAM-1+
      endothelial cells in 8.7% of vessels. After 24 h of organ culture in medium
      supplemented with tumor necrosis factor and interleukin-4, ELAM-1+ endothelial
      cells in the SVP were increased significantly in uninvolved (from mean 0.5% to
      27% of vessels), perilesional (from mean 5.5% to 41.8% of vessels), and lesional
      skin (from mean 29.4% to 45.7% of vessels). VCAM-1 was not inducible on SVP
      endothelial cells in uninvolved skin but VCAM-1+ endothelial cells were increased
      significantly in perilesional (from mean 0.7% to 23.7% of vessels) and lesional
      skin (from mean 8.7% to 41.4% of vessels). In uninvolved and perilesional skin
      ELAM-1 and VCAM-1 were confined to endothelial cells below the rete. In contrast,
      endothelial cells of the intrapapillary part of the capillary loop of lesional
      skin became cytokine responsive, in that ELAM-1 and VCAM-1 could be induced at
      this site. By immunoelectron microscopy, expression was most intense on the
      luminal surface of venular endothelial cells and at the interendothelial
      junctions. In conclusion, we have presented evidence that the cytokine
      responsiveness of microvascular endothelial cells is altered in psoriasis in a
      pattern that may explain both the circumscribed nature and the epidermal
      involvement of the psoriatic plaque.

PMID- 7521376
TI  - Expression of Fas antigen on keratinocytes in vivo and induction of apoptosis in
      cultured keratinocytes.
AB  - Fas antigen, which belongs to a nerve growth factor/tumor necrosis factor
      receptor superfamily, is a membrane protein that induces apoptosis. In humans,
      distribution of Fas antigen has been reported on cell lines and lymphocytes.
      Immunohistochemical studies revealed Fas antigen on the keratinocytes of lesional
      epidermis in lichenoid drug eruption, erythema multiforme, contact dermatitis,
      bullous pemphigoid, pemphigus vulgaris, and herpes zoster; it is co-expressed
      with intercellular adhesion molecule-1. Cultured keratinocytes expressing Fas
      antigen increased from 8.4% to 34.6% after stimulation with interferon gamma for
      24 h. Treatment of interferon-gamma-stimulated keratinocytes with anti-Fas for 48
      h resulted in DNA fragmentation and death of 32% of cells, suggesting that Fas
      antigen may mediate apoptosis. The expression of Fas antigen on keratinocytes in
      lesional skin suggests that death via Fas antigen may play an important role in
      the pathogenesis of keratinocyte cytotoxicity.

PMID- 7521375
TI  - Differential expression of genes encoding a cysteine-rich keratin family in the
      hair cuticle.
AB  - In the hair follicle the cuticle develops as a thin layer of cells between the
      hair shaft cortex and the inner root sheath. Once the cuticle cells begin to
      differentiate they accumulate cysteine-rich granules in their cytoplasm but the
      identity of their constituent proteins has remained largely an enigma. In this
      report we show differential expression of a family of genes encoding cysteine
      rich, glycine-rich keratins in the cuticle. Two clones of the sheep KAP5 gene
      family were isolated: the KAP5.4 cDNA encodes a protein of 190 amino acids (M(r)
      = 16,936) containing 32 mol% cysteine, 26 mol% glycine and the partial KAP5.5
      cDNA encodes a protein of at least 197 amino acids (M(r) > or = 17,474)
      containing 29 mol% cysteine, 28 mol% glycine. The predicted amino acid sequences
      of the KAP5 family show extensive sequence conservation and all the proteins are
      composed almost entirely of cysteine-rich and glycine-rich repeats. Each KAP5
      gene produces an approximately 1.5-kb mRNA species but the KAP5.4 and KAP5.5 mRNA
      levels appear to be severalfold greater than the KAP5.1 mRNA. Comparative tissue
      in situ hybridizations reveal a positive correlation between the onset of
      expression and follicle depth. For a given KAP5 gene two widely different cuticle
      expression patterns were noted amongst the follicle populations, and on the basis
      of follicle bulb cell kinetics they are consistent with expression in either
      sheep primary or secondary follicle types.

PMID- 7521377
TI  - Long-term follow-up study of serum IgM antibody to hepatitis C virus (HCV), HCV
      replication, and liver disease outcome in chronic hepatitis C.
AB  - IgM anti-hepatitis C virus (HCV) and HCV RNA were longitudinally tested for 4.0
      8.7 years in 40 patients with chronic HCV infection. Patients in disease
      remission usually lost IgM anti-HCV and HCV RNA, but most patients experiencing
      disease reactivation had increased levels of the IgM antibody or it reappeared
      before the biochemical relapse, even when HCV RNA was undetectable. IgM anti-HCV
      was detectable in most patients with ongoing viral replication and persistent
      liver disease. Despite long-term disease remission, IgM anti-HCV may persist and
      be detectable with or without evidence of serum HCV RNA; this indicates a
      possible disease reactivation, which could occur after several years of sustained
      transaminase normalization. Detection of IgM anti-HCV in chronic hepatitis C
      indicates an active immune response to persistent viral infection and should,
      therefore, be considered as a sensitive marker of active HCV replication and HCV
      associated liver disease.

PMID- 7521378
TI  - Nitric oxide synthase and antimicrobial armature of human macrophages.

PMID- 7521379
TI  - Histochemical studies on the effect of propoxur on yolk synthesis in the
      ovarioles of the blow fly, Chrysomyia albiceps (Wiedemann) (Diptera:
      Calliphoridae).
AB  - The effect of the carbamate insecticide, propoxur, on yolk synthesis in the
      ovarioles of the blow fly, Chrysomyia albiceps (Wiedemann) was studied.
      Histochemical studies showed that DNA, RNA, protein and lipid synthesis in
      propoxur--treated ovarioles decreased as compared to that in non-treated
      ovarioles, with some deteriorations in the chromatin materials in the nuclei of
      some nurse cells. On the other hand, the synthesis of carbohydrate is more or
      less not affected.

PMID- 7521380
TI  - Pneumocystis carinii: recognition of the infection in albino rats using different
      stains.
AB  - Pneumocystis carinii is a commensal protozoan which may cause pneumonia in hosts
      with compromised immune status and may end fatally. Since effective management of
      pneumocystic pneumonia depends on rapid and accurate recognition of the disease,
      so, the present study aims to throw lights on the best staining method for
      cytodiagnosis of this organism with the sequential pathological changes in the
      infected lungs. An immunosuppression state was induced in albino rats for 6-8
      weeks then rats were sacrificed weekly & lungs were examined for infection using
      different stains. In stained smears, intracystic bodies have been identified
      using Giemsa, Papanicolaou & Toluidine blue stains. On the other hand, cysts were
      inspected in paraffin sections using Gomori methenamine silver nitrate (GMS) &
      weight gram stains. Histopathologically, in sections stained with H & E, features
      of Pneumocystis carinii pneumonia were obvious, foamy exudation, inflammatory
      infiltration formed mainly of histiocytes, plasma cells, lymphocytes, thickening
      of alveolar septa and lastly formation of hyaline membrane in some alveoli.

PMID- 7521381
TI  - Purification and characterization of a specific Fasciola antigen.
AB  - Specific Fasciola antigen was prepared from homogenates of Fasciola hepatica
      adult worms. The homogenate was ultracentrifuged and the supernatant containing
      crude Fasciola antigen was then passed over a cyanogen bromide activated
      sepharose 4B column coupled with antiserum against Schistosoma mansoni adult worm
      surface antigen. The specific, Schistosoma-free Fasciola antigen was tested for
      its specificity by immunodiffusion. Characterization of the specific Fasciola
      antigen was done by gradient poly-acrylamide gel electrophoresis and
      immunoblotting technique. The electrophoresis migration pattern of specific
      Fasciola antigen, stained with Coomassie blue, showed 7 bands in the 12-54 kDa
      regions. Using the immunoblotting technique, a batch of positive fascioliasis
      sera recognized two specific bands at the 33 and 54 kDa regions.

PMID- 7521383
TI  - Iloprost, stable analogue of the prostacyclin, is able to improve the tissue
      resistance to ischaemia.
AB  - On 10 patients, suffering from peripheral arterial disease, with critical limb
      ischaemia, the CO2 production during ischaemia has been evaluated at 1st and at
      28th day of treatment with iloprost. The study demonstrated that the drug is able
      to improve the tissue resistance to ischaemia, with a significant (p < 0.05)
      reduction of the CO2 production. The authors underline that this study is one of
      the first confirmations, in vivo and on the man, of the previous experimental
      findings, made in isolated arterial tissue.

PMID- 7521384
TI  - Evaluation of a conservative treatment with iloprost in severe peripheral
      occlusive arterial disease (POAD). GISAP Study.
AB  - GISAP, a multicentre open study, was aimed to confirm the feasibility and safety
      of iloprost treatment in normal clinical practice and to identify subgroups of
      patients with severe POAD more likely to benefit from iloprost treatment than
      others. One hundred forty six patients were treated at the maximum tolerated dose
      of iloprost up to 2 ng/kg/min, 6 hours infusion per day, for a minimum of 3 weeks
      and a maximum of 8 weeks. Clinical efficacy was assessed by rest pain reduction,
      analgesic consumption, healing of trophic lesions, walking ability. A significant
      improvement of the efficacy parameters was recorded during and at the end of
      treatment: no difference between diabetics and non diabetics, stage III and IV
      patients was observed. After one year follow-up 10% major amputation and 6.8%
      death were recorded, these events were balanced between the diabetic and non
      diabetic patients. Overall 80% of the patients at risk of amputation at entry to
      the trial were alive with a viable limb after one year. Tolerability resulted
      quite acceptable. Even with the limitation of an open trial, it has been
      confirmed the therapeutic potential of iloprost in the treatment of POAD
      patients.

PMID- 7521382
TI  - Chicken interferon gene: cloning, expression, and analysis.
AB  - A gene encoding chicken interferon (ChIFN) was cloned from a cDNA library made
      from primary chick embryo cells that had been "aged" in vitro so as to produce
      copious amounts of IFN upon induction. The coding region is predicted to produce
      a signal peptide of 31 amino acids and a mature protein of 162 amino acids with a
      molecular weight of 18,957. There are four potential N-glycosylation sites and
      six cysteine residues. Three disulfide bonds are possible, with two being common
      to most mammalian type I IFNs. A motif of 10 amino acids surrounding Cys-137 is
      highly conserved: It shows 80% homology with mammalian type I IFNs, but only 30%
      with a reported fish IFN. The T-rich 3' UTR displays the canonical element AATAAA
      required for polyadenylation, and contains six repeats of the octamer CTATTTAT
      that may be involved in down-regulating translation. Northern blots demonstrate
      that the accumulation of ChIFN mRNA correlates with induction of ChIFN determined
      by bioassay. Biologically active protein was synthesized in transfected mouse L
      cells using mRNA prepared in vitro from the cloned sequence. This activity was
      neutralized by a monoclonal antibody prepared against purified ChIFN. The ChIFN
      gene shows sequence identity at the amino acid/nucleotide level with consensus
      mammalian IFNs as follows: alpha (24/23%), beta (20/24%), omega (23/43%), tau
      (20/43%), gamma (3/31%), and with flatfish IFN (16/35%). The conserved features
      of the predicted ChIFN protein and the general similarity of predicted secondary
      structure suggest a molecule that fits the five alpha-helix three-dimensional
      topology reported for type I mammalian IFNs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521385
TI  - Hepatic lipase gene is transcribed in rat adrenals into a truncated mRNA.
AB  - Rat adrenals contain a lipase activity that is indistinguishable from hepatic
      lipase (HL) present in liver. Expression of HL mRNA in adrenals was studied using
      the method of reverse transcription-polymerase chain reaction (RT-PCR). A 596-bp
      fragment of HL cDNA spanning exons 5 to 8 was amplified when using total RNA from
      rat adrenals and liver, but not from heart or kidney. The abundance of HL mRNA
      was quantified by competitive RT-PCR using a standard RNA that was generated in
      vitro by transcription from a deleted HL cDNA construct. Adrenals contained 0.4
      attomoles of HL mRNA per microgram of total RNA, compared to 16 attomoles in
      liver. In hypertrophic adrenals isolated from corticotrophin-treated rats, the
      abundance also amounted to 0.4 attomoles of mRNA per microgram of total RNA.
      However, amplification of full-length cDNA from either control or hypertrophic
      adrenals was never observed. Detailed analysis by PCR using different
      combinations of primers indicated that exons 3 to 9 including the 3'-untranslated
      region were expressed in adrenal RNA, but not the first two coding exons. The
      upstream part of the adrenal lipase mRNA was cloned after rapid amplification of
      cDNA ends (RACE). The resulting clones showed a unique 126-bp sequence 5' of the
      exon 2-exon 3 junction. This sequence contained multiple termination codons in
      all three reading frames but lacked a potential start codon. RT-PCR using an HL
      specific primer and an oligonucleotide directed against this 5'-sequence showed
      that it is not only expressed in RNA from adrenals but also in liver. Pulse
      labeling of freshly isolated adrenocortical cells with [35S]methionine followed
      by immunoprecipitation with anti-HL antibodies failed to show synthesis of mature
      HL, but indicated the synthesis of immunoreactive proteins in the 40-45 kDa range
      that remained mainly intracellular. Hence, the HL gene is transcribed in adrenals
      but results in an mRNA species with a unique 5'-end. Translation from an internal
      start site may produce an intracellular HL isoform that differs markedly from the
      liver-type lipase previously identified in adrenals.

PMID- 7521386
TI  - Rapid quantitation of mRNA species in ethidium bromide-stained gels of
      competitive RT-PCR products.
AB  - A rapid method for quantifying the low-abundant mRNAs of the low density
      lipoprotein receptor and the 3-hydroxy-3-methylglutaryl coenzyme A reductase by
      competitive polymerase chain reaction is presented. This approach requires
      neither special labeling nor blotting procedures. For each analysis, a defined
      amount of total cellular RNA is co-reverse transcribed and co-amplified with a
      titration series of in vitro synthesized competitor RNA that carries an internal
      deletion. The equivalence point, which defines the amount of specific RNA in the
      sample, can be scored in ethidium bromide-stained agarose or polyacrylamide gels
      of the reaction products. As an example, responses to pravastatin, a competitive
      inhibitor of the HMG-CoA reductase, in a human tumor cell line were analyzed with
      this new technique. As a control, the expression of the unregulated gene,
      glyceraldehyde-3-phosphate dehydrogenase was measured in parallel using the same
      methodology. The results obtained were compared with those obtained by
      conventional Northern blotting.

PMID- 7521387
TI  - Selective staining of the superficial cells of mouse urinary bladder epithelium
      by horseradish peroxidase (HRP).
AB  - A simple method for staining the superficial cells of mouse urinary bladder
      epithelium with horseradish peroxidase (HRP) is presented. HRP solution was
      instilled into the bladder lumen in vivo. After fixation with glutaraldehyde, the
      bladder was treated with Triton X-100 and then reacted with diaminobenzidine
      (DAB). Intense DAB reactions were detected throughout the whole of the cytoplasm
      of superficial cells by both light and electron microscopy. No reaction was
      observed in intermediate or basal epithelial cells. This simple method will be
      useful for the three-dimensional reconstruction of cell shape and identification
      of the stratification of transitional epithelial cell layers.

PMID- 7521389
TI  - Hepatitis C experience at a community teaching hospital.
AB  - BACKGROUND: The purpose of this study was to review the initial serologic testing
      experience for hepatitis C (HCV) and physician response at a community teaching
      hospital. METHODS: A retrospective chart review was performed for the 59 (5%) HCV
      positive patients of 1244 patients who were tested by means of a new enzyme
      immunosorbent assay (EIA) for HCV antibodies between October 28, 1990, and
      October 27, 1991. RESULTS: Physicians identified HCV risk factors, including
      intravenous drug use (n = 14, 25%) and having received blood products (n = 15,
      27%). One half of the patients were not queried about the known risk factors for
      HCV. The most common reason for ordering an HCV assay was elevated liver enzymes.
      None of the patients underwent supplementary HCV testing (ie, polymerase chain
      reaction or recombinant immunoblot assay). In 23 (40%) of the HCV-positive
      patients, no action was taken by the physician, and 15 (27%) were lost to follow
      up. The remaining 18 patients (33%) had further follow-up with laboratory or
      treatment. CONCLUSIONS: These results indicate the need for increased physician
      awareness of risk factors for HCV and improved documentation of these factors in
      taking patient history. In addition, primary care physicians need to be educated
      about new laboratory tests and how to interpret test results and when to order
      supplemental testing.

PMID- 7521388
TI  - PSA screening.

PMID- 7521390
TI  - Persistent influenza C virus possesses distinct functional properties due to a
      modified HEF glycoprotein.
AB  - A model of long term viral persistence has been established by selecting a
      spontaneous mutant strain of influenza C/Ann Arbor/1/50 virus in a permanent
      carrier culture of MDCK cells. Infectivity and cell tropism are mainly determined
      by the multifunctional viral membrane glycoprotein (HEF). HEF analysis was aimed
      at identifying a putative correlation between sequence and function, i.e.
      receptor binding, enzymatic activity, antigenicity and rate of infection. The
      current experimental picture is summarized by the following findings: (i) C/Ann
      Arbor/1/50 persistent virus carries a modified receptor-binding sequence, (ii)
      receptor-binding activity is altered, as indicated by a higher efficiency in
      recognizing low amounts of the receptor determinant N-acetyl-9-O-acetylneuraminic
      acid, (iii) direct attachment to cell surfaces differs from that of wild-type
      virus, as measured by slower kinetics of viral elution, (iv) receptor-destroying
      enzymatic activity is diminished, (v) characteristic features of virion surface
      morphology are altered or unstable, (vi) persistent-type HEF epitopes are
      distinguishable by monoclonal antibodies from wild-type and (vii) viral
      infectivity is intensified for cells bearing a low number of receptors. The sum
      of these changes highlights a structurally and functionally modified HEF
      glycoprotein that allows long term viral persistence. In order to clarify which
      of the described points are required for the persistent viral phenotype, a
      working concept is presented.

PMID- 7521393
TI  - Assembled baculovirus-expressed human papillomavirus type 11 L1 capsid protein
      virus-like particles are recognized by neutralizing monoclonal antibodies and
      induce high titres of neutralizing antibodies.
AB  - Baculovirus-expressed human papillomavirus type 11 (HPV-11) major capsid protein
      (L1) virus-like particles (VLPs) were produced in insect cells and purified on
      CsCl density gradients. The VLPs retained conformational neutralizing epitopes
      that were detected by a series of HPV-11-neutralizing monoclonal antibodies.
      Electron microscopy determined that the HPV-11 L1 VLPs were variable in size with
      a surface topography similar to that of infectious HPV-11. The VLPs were very
      antigenic, and induced high titres of neutralizing antibodies in rabbits and mice
      when used as an immunogen without commercial preparations of adjuvant. These VLP
      reagents may be effective vaccines for protection against HPV infections.

PMID- 7521391
TI  - T cell proliferative response to bovine leukaemia virus (BLV): identification of
      T cell epitopes on the major core protein (p24) in BLV-infected cattle with
      normal haematological values.
AB  - Peripheral blood mononuclear cells (PBMCs) from bovine leukaemia virus (BLV)
      seronegative cattle and from BLV-seropositive cows either with normal
      haematological values or persistent lymphocytosis were tested for their
      proliferative response to BLV antigens. Cells from only BLV-infected cattle with
      normal lymphocyte counts were stimulated to a detectable level by the fetal lamb
      kidney cell supernatant containing BLV antigens. Proliferation assays performed
      with the purified major core protein p24 indicated that this protein has to be
      processed through a chloroquine-sensitive compartment before being recognized by
      CD4+ T lymphocytes. Forty-one 15-mer overlapping peptides spanning the entire p24
      sequence were synthesized and analysed for their stimulating potential. It
      appeared that two regions included T cell epitopes recognized by PBMCs from three
      of five animals tested. These regions were represented by amino acids 31 to 55
      (PGSQVWIQTLRLAILQADPTPADLE) and 141 to 165 (AESYVEFVNRLQISLADNLPDGVPK). The
      possible implication of this cell-mediated immune response in BLV pathogenesis
      and vaccine development is discussed.

PMID- 7521392
TI  - Persistent infection of MT-4 cells by human immunodeficiency virus type 1 becomes
      increasingly likely with in vitro serial passage of wild-type but not nef mutant
      virus.
AB  - Our previous studies have shown that human immunodeficiency virus type 1 (HIV-1),
      with mutations in accessory genes such as vif, vpr or vpu, can generate
      persistent infection of MT-4 cells, whereas infection by wild-type or nef mutant
      HIV-1 causes extensive cell death. The possibility of generating a naturally
      attenuated form of HIV-1 with reduced cytopathogenicity in MT-4 cells was
      examined by in vitro serial passage of the wild-type and a nef mutant form of HIV
      1, each derived from the infectious molecular clone pNL432. The ability to cause
      persistent infection was observed after four passages of wild-type HIV-1 with the
      frequency of persistence becoming progressively higher with serial passage. In
      contrast, persistent infection was not observed even after 50 passages of the nef
      mutant virus. Sequence analysis of the accessory gene loci in genomes recovered
      from the persistent infections caused by passaged virus revealed mutations in vif
      and vpr, but not in vpu. The processing of the Env precursor to mature forms was
      not modified in any of the passages of either wild-type or nef mutant HIV-1.
      However, when compared with acute infections caused by similarly passaged virus
      of both wild-type and nef mutant HIV-1, persistent infections by passaged wild
      type HIV-1 showed a significant decrease in the cell surface expression and
      function of Env. Cell surface CD4 was only partially down-regulated on cells
      acutely infected with the passaged viruses, whereas on cells persistently
      infected with passaged wild-type HIV-1 it was completely down-regulated. These
      results suggest that, during serial passage of HIV-1, mutations accumulate at
      least in the accessory genes vif and vpr in parallel with a lesser interaction
      between cell surface Env and CD4 molecules, and lead to the generation of less
      cytopathogenic viruses capable of persistent infection. Our results also suggest
      an important role for the nef gene product in the generation of HIV-1 strains
      that are less cytopathogenic.

PMID- 7521394
TI  - Five new cytotoxic T cell epitopes identified within Epstein-Barr virus nuclear
      antigen 3.
AB  - Epstein-Barr virus (EBV) CD8+ cytotoxic T lymphocyte (CTL) epitopes are currently
      being considered for inclusion into subunit vaccines. Here we describe the
      characterization of five new CTL epitopes within EBV nuclear antigen 3 (EBNA3),
      confirming EBNA3 as a major target for CTL recognition.

PMID- 7521395
TI  - Combination chemotherapy of 5-fluorouracil, epidoxorubicin and mitomycin C in the
      palliative treatment of locally advanced and/or metastatic adenocarcinoma of the
      stomach.
AB  - Thirty-seven consecutive patients with advanced and/or metastatic gastric
      adenocarcinoma received a combination of 5-fluorouracil 600 mg/m2 on days 1, 8,
      29, 36; epidoxorubicin 75 mg/m2 i.v. on days 1, 29; mitomycin C 10 mg/m2 i.v. on
      day 1. This cycle was repeated every 8 weeks. Out of a total of 34 evaluable
      patients, 2 (5.8%) had a complete response and 7 (20.6%) had a partial response
      with an overall median duration of 40 weeks (range 20-128). The median survival
      of responding patients was not reached after a mean follow-up of 76 weeks, while
      that of patients with no change and progressive disease was reached at 36 and 13
      weeks respectively. Treatment was generally well tolerated with hematological and
      gastrointestinal toxicities being the major side-effects. Despite the use of
      epidoxorubicin 75 mg/m2, the 26.4% (95% confidence limits 16-36%) objective
      response rate is not satisfactory. Evaluation of more aggressive protocols is
      strongly recommended within the limits of controlled trials.

PMID- 7521396
TI  - Extrahepatic biliary atresia: a first-trimester event? Clues from light
      microscopy and immunohistochemistry.
AB  - Biliary atresia is an obliterative disorder of the bile ducts, causing
      obstructive jaundice in neonates. In this study, the developing biliary system of
      normal human embryos and fetuses was examined and compared with the resected
      extrahepatic biliary remnants from 205 cases of biliary atresia. At the porta
      hepatis level, it was found that the primary biliary ductal plate undergoes a
      specific sequence of remodelling, resulting in the formation of large tubular
      bile ducts surrounded by thick mesenchyme, between 11 and 13 weeks
      postfertilisation. These developing ducts are in luminal continuity with the
      extrahepatic biliary tree throughout gestation. Contrary to long-held belief, no
      "solid phase" was observed in the development of the extrahepatic bile duct.
      Examination of the biliary remnants in biliary atresia showed that the porta
      hepatis is encased in fibrous tissue, and a variable pattern of obliteration of
      the common hepatic and common bile ducts was observed. Anticytokeratin
      immunostaining showed similarities between the abnormal ductules within the porta
      hepatis in biliary atresia, and the developing bile ducts in the first trimester.
      Biliary atresia may be caused by failure of the remodelling process at the
      hepatic hilum, with persistence of fetal bile ducts poorly supported by
      mesenchyme. As bile flow increases perinatally, bile leakage from these abnormal
      ducts may trigger an intense inflammatory reaction, with subsequent obliteration
      of the biliary tree.

PMID- 7521397
TI  - 1H-NMR assignment and solution structure of human acidic fibroblast growth factor
      activated by inositol hexasulfate.
AB  - A major fragment of human acidic fibroblast growth factor of 132 amino acid
      residues is shown to be as active and stable as the 139 residue molecule
      initially described, and commonly used in physiological studies. It is shown that
      inositol hexasulfate is a good substitute for heparin in both activating and
      protecting acidic fibroblast growth factor. The complex between the shortened
      form of the protein and inositol hexasulfate was used to determine the structure
      of activated acidic fibroblast growth factor in solution. The 1H-NMR spectrum of
      the complex was totally assigned, and a low-resolution, three-dimensional
      structure of the protein computed. The global fold of the activated acidic
      fibroblast growth factor is similar to that proposed for a crystallized variant
      of the protein obtained by genetic engineering whose activity is not dependent on
      heparin. The inositol hexasulfate binds to the protein through the positively
      charged groups of Lys126, Lys127, Arg133 and Lys142 side-chains. The computed
      three-dimensional structure suggests that inositol hexasulfate may stabilize and
      activate the protein by conferring rigidity to the hairpin involving beta-strands
      10 and 11.

PMID- 7521398
TI  - The use of colony-stimulating factors as bone marrow support for systemic
      anticancer chemotherapy.
AB  - Colony-stimulating factors (CSFs) are proteins that play normal roles in human
      hematopoietic physiology. Many of these factors have been cloned and sequences.
      This has led to recombinant DNA technology that now allows for production of
      large quantities of pharmacologically pure compounds. Granulocyte colony
      stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor
      (GM-CSF) are two such compounds that have been approved by the US Food and Drug
      Administration for human use in specific medical circumstances. This article
      summarizes the experience of one institution in using these two CSFs and adds
      brief commentary on four other CSFs that are expected to come to general use in
      the near future--interleukin-1, interleukin-3, interleukin-6, and erythropoietin.
      Both G-CSF and GM-CSF are effective in protecting patients from the leukotoxic
      effects of cancer chemotherapy, but GM-CSF appears to have a comparatively narrow
      "dosing window," wherein the agent is effective and tolerable. Future studies
      should address combining these agents with platelet protective compounds to
      improve patient safety.

PMID- 7521399
TI  - Isolation, characterization, and expression of cDNA clones that encode rat UDP
      galactose: ceramide galactosyltransferase.
AB  - UDP-galactose:ceramide galactosyltransferase (CGT) (EC. 2.4.1.62) catalyzes the
      final step in the synthesis of galactocerebroside (GalC), a glycosphingolipid
      found in high amounts in the myelin sheath. Here, the isolation of rat CGT
      specific cDNA clones is reported. The CGT sequence contains an open reading frame
      of 1,623 bp which predicts a protein of M(r) 61,126 Da. In transfection
      experiments the cDNA was found to confer CGT activity to Chinese hamster ovary
      cells. In rat brain the developmental expression pattern of CGT mRNA was similar
      to the myelination profile, whereas the sciatic nerve contained high amounts of
      CGT message over a long developmental period. CGT mRNA expression in the sciatic
      nerve was found to drop substantially following nerve injury and recover slowly
      when compared to the expression of mRNAs specific for the predominant myelin
      specific proteins. The absolute amounts of CGT message in sciatic nerve and brain
      were found to be comparable to those that encode the structural proteins of
      myelin. Except for low amounts in the kidney, the CGT mRNA was not detected in
      other tissues examined. Southern blot analysis revealed that the CGT protein is
      likely encoded by a single, relatively large gene.

PMID- 7521400
TI  - Screening for prostate cancer. A decision analytic view.
AB  - OBJECTIVE: To determine the clinical and economic effects of screening for
      prostate cancer with prostate-specific antigen (PSA), transrectal ultrasound
      (TRUS), and digital rectal examination (DRE). DESIGN: Decision analytic cost
      utility analysis comparing four screening strategies with a strategy of not
      screening. We assumed that the cancer detection rate and stage distribution were
      predicted by each combination of tests and that localized cancer was treated with
      radical prostatectomy. For each strategy, we calculated life expectancy, quality
      adjusted life expectancy (QALE), and cost-utility ratios for unselected and high
      prevalence populations. DATA: Probabilities and rates for clinical events were
      gathered from published data. We assessed utilities by the time-trade-off method
      using urologists, radiation oncologists, and internists as subjects. The Clinical
      Cost Manager at the New England Medical Center provided cost data. RESULTS: In
      unselected men between the ages of 50 and 70 years, screening with PSA or TRUS
      prolonged unadjusted life expectancy but diminished QALE. Screening with DRE
      alone yielded no reduction in mortality at any age. All programs increased costs.
      Results were sensitive only to assumptions about the efficacy of treatment. In
      high-prevalence populations, screening produced a similar pattern: gains in
      unadjusted life expectancy, losses in QALE, and increased costs. CONCLUSIONS: Our
      analysis does not support using PSA, TRUS, or DRE to screen asymptomatic men for
      prostatic cancer. Screening may result in poorer health outcomes and will
      increase costs dramatically. Assessment of comorbidity, risk attitude, and
      valuation of sexual function may identify individuals who will benefit from
      screening, but selecting high-prevalence populations will not improve the benefit
      of screening.

PMID- 7521401
TI  - Neurodevelopment after in utero exposure to phenytoin and carbamazepine.

PMID- 7521402
TI  - Neurodevelopment after in utero exposure to phenytoin and carbamazepine.

PMID- 7521403
TI  - [CD7 positive acute myelogenous leukemia exhibiting pleural involvement as an
      initial manifestation].
AB  - A 51-year-old man had suffered from massive pleural effusion due to invasion of
      malignant cells. The analysis of bone marrow aspiration showed the proliferation
      of myeloperoxidase-positive blasts. The surface marker analysis of the blasts
      revealed the positivities for CD7 and CD19 as well as CD13, CD33 and CD34, while
      the karyotypes of 20 cells were normal. Therefore, CD7 positive AML was
      diagnosed. The patient was treated with araC and daunorubicin as a remission
      induction therapy. Peripheral blood stem cells were harvested by leukapheresis
      after first and second consolidation therapies. Then, 3 x 10(4) cells/kg of CFU
      GM were infused. Complete remission has been maintained for 8 months after
      autologous blood stem cell transplantation. Pleural involvement as an initial
      manifestation is rare in AML. Extramedullary growth of AML cells may be related
      to their immaturity, indicated by the expression of the cell surface antigens.

PMID- 7521404
TI  - [Virus-associated hemophagocytic syndrome due to rubella virus in an adult].
AB  - A 57-year-old woman was admitted to our hospital because of fever and eruption.
      On admission, her white blood cell count was 1,600/ml, and platelet count 1.7 x
      10(4)/ml. Ferritin and lysozyme were elevated. Bone marrow aspiration showed 4%
      histiocyte with hemophagocytosis. The anti-rubella virus antibody titer was 1:64,
      and that at convalescence stage was 1:254. Therefore, she was diagnosed to have
      virus-associated hemophagocytic syndrome (VAHS). Steroid (methylprednisolone
      1,000 mg x 3 days) and gamma globulin therapy were initiated. Her clinical
      condition and laboratory data were promptly improved. Thus, it was suggested that
      steroid-pulse and gamma globulin therapy are effective in the early stage of this
      syndrome in adult.

PMID- 7521405
TI  - [Effects of cytarabine ocfosfate on colony-stimulating factor in myelodysplastic
      syndrome with monosomy 7].
AB  - A 42-year-old man was admitted to our hospital because of pancytopenia in April
      1992. A diagnosis of refractory anemia was made. The karyotype was normal male
      type on the initial study. Subcutaneous administration of granulocyte colony
      stimulating factor (G-CSF) initially increased the peripheral neutrophil count,
      bat in January 1993, although blast cells did not increase, neutrophils had
      decreased in spite of the continuation of G-CSF administration. Chromosome
      analysis showed 46XY, +Y, -7 at this point. By adding 50 mg of cytarabine
      ocfosfate (SPAC) daily, the peripheral neutrophil count again rose dramatically.
      However, anemia, thrombocytopenia and the chromosomal abnormality were unchanged.
      These results indicate that SPAC may upregulate the effect of G-CSF on
      granulopoiesis in patients with myelodysplastic syndrome.

PMID- 7521406
TI  - [Recent and future aspects of interferon therapy for hepatitis type C].

PMID- 7521408
TI  - [Fluctuation of HCV quasi-species population during interferon therapy; analysis
      by single strand conformation polymorphism].
AB  - We investigated the fluctuation of hepatitis C virus (HCV) quasispecies during
      interferon therapy by single strand conformation polymorphism (SSCP) analysis. In
      13 of 16 interferon ineffective patients, the predominant HCV population was
      replaced with other quasispecies during the treatment. Especially, in 9 patients,
      a part of the HCV quasispecies, pre-existing before interferon therapy, became
      predominant after the therapy. These results indicate that sensitivity to
      interferon differs among HCV quasispecies and that interferon selects resistant
      HCV strains. Existence of such HCV quasispecies seems to be associated with
      interferon treatment failure.

PMID- 7521409
TI  - [Serial amino acid sequence change in the hypervariable region of hepatitis C
      virus].
AB  - The hypervariable region 1 of the hepatitis C virus genome has attracted much
      scientific interest as higher degrees of variability of the region have been
      reported to be a predictive factor of poor response to interferon treatment. We
      analyzed sequential changes in the amino acid sequence of this region before,
      during and after two courses of interferon treatment. A major strain seen before
      treatment was overtaken by another strain which had been a relatively minor
      population before therapy. Later a transient emergence of two minor populations
      was observed during interferon treatment. We also found that the disappearance of
      some strains could be explained by cloning artifact due to polymerase chain
      reaction (PCR). Such artifact should be taken into account when analyzing this
      region by means of PCR.

PMID- 7521407
TI  - [PCR-based HCV genotyping with type-specific primers derived from core gene and
      IFN responsiveness].
AB  - Based on the sequence similarity of HCV isolates for which the entire nucleotide
      sequence is determined, at least five genotypes of HCV (I, II, III, IV and V)
      have been reported which differ from each other in more than 21% of approximately
      9.4 kilobases. HCV genomes are classifiable into the five defined genotypes by
      PCR amplification with type-specific primers derived from core gene. Genotype of
      HCV appears to an important factor in determining the response to IFN in patients
      with chronic hepatitis C. It would be worthwhile to genotype HCV in pretreatment
      sera, for correlation with therapeutic efficacy of IFN for chronic hepatitis C,
      in districts where HCV variants with unclassifiable genotypes are prevailing and
      therapeutic trials are planned.

PMID- 7521410
TI  - [Genomic changes in the E2/NS1 region of HCV before and after IFN therapy in
      relation to clinical course].
AB  - To estimate the relationship between genomic change in the E2/NS1 region and
      clinical feature, we made a pairwise comparison in the nucleotide and deduced
      amino acid sequences for multiple recombinant clones of the E2/NS1 region, which
      derived from blood samples taken from four patients (three treated by IFN) at
      different stages. Sequence heterogeneities among the clones were generally high
      but they appeared to be significantly lowered after cessation of therapy. Our
      results showed, through IFN therapy, a few clones were selected and survived,
      although many clones disappeared. After discontinuation of the drug, three
      patients became carrier state, normal ALT levels with viremia. Evolution of
      defective viruses was seen in most of the cases. These features of HCV genome
      suggest that the virus could circulate as an extremely heterogeneous population
      including defective virus, and that this heterogeneity lend itself to selection
      pressures including interferon therapy and host immune response.

PMID- 7521411
TI  - [Specific antibody assay for genotyping of hepatitis C virus].
AB  - Based on their nucleotide sequences and the deduced amino acid sequences, most
      hepatitis C virus (HCV) isolates have been classified into two genotypes, type 1
      (subtype 1a and 1b) and type 2 (subtype 2a and 2b). Using part of the putative
      NS4 protein region (amino acids No. 1676-1760) as antigens, an enzyme-linked
      immunosorbent assay (ELISA) was developed. The results of genotyping of HCVs in
      chronic hepatitis patients by this ELISA system were almost completely consistent
      with those by PCR. The genotype 1 HCV infected patients showed a poor response to
      interferon (IFN) therapy. In contrast, genotype 2 HCV infected patients showed
      good response. The results suggest that genotype 1 and 2 HCVs possess different
      biological properties.

PMID- 7521412
TI  - [HCV-serotype and IFN response].
AB  - The relation between HCV-serotypes and response to interferon (IFN) in 114 cases
      with chronic hepatitis C treated with IFN-alpha were studied. HCV-serotypes; two
      distinct subgroups (serotype 1 and 2) of hepatitis C virus defined by antibodies
      directed to the putative core protein, were examined by ELISA developed by
      Machida et al. 1) Of 33 cases with serotype 2, 20 were responders, whereas, only
      5 of 35 cases with serotype 1 responded to IFN therapy. 2) Of 23 cases with HCV
      genotype III, 18 (78.3%) responded to IFN. Moreover, 12 (85.7%) of 14 cases who
      had serotype 2 were responders. On the other hand, only 17 (21.0%) cases with
      genotype II and 4 (12.1%) cases with serotype 1 responded to IFN. HCV-serotyping
      as well as HCV-genotyping in cases with chronic hepatitis C seems to be important
      in predicting the response to IFN therapy.

PMID- 7521413
TI  - [Classification of hepatitis C virus into two major groups in serologic activity:
      correlation with response to interferon].
AB  - Genotypes of HCV have been reported to be one of the predictors of response to
      IFN therapy in patients with chronic hepatitis C. HCV genotypes were determined
      enzyme-linked immunoblot assay based on group I and II specific recombinant
      peptides of the NS-4 region (amino acid No. 1676-1670). We examined the
      correlation between HCV groups and response to IFN in patients with chronic
      hepatitis C. Among the 84 patients with chronic hepatitis C who underwent IFN
      treatment, 16 of 51 (31.4%) patients with group I and 12 of 23 (52.2%) patients
      with group II showed complete sustained response. These results suggest that HCV
      group assay may improve the ability to predict IFN treatment outcomes.

PMID- 7521414
TI  - [Serum levels of HCV-RNA determined by branched DNA (bDNA) probe assay in chronic
      hepatitis C: method and clinical significance on interferon (IFN) therapy].
AB  - Recently serum levels of HCV RNA (s-HCV RNA) in chronic hepatitis C has been
      regarded as one of an important indicator for the activity of disease and outcome
      of IFN therapy. Quantitative analysis by competitive RT-PCR, however, requires
      special skills and is too expensive for clinical use. We attempted to determine
      serial sample of s-HCV RNA and genotypes in 117 cases treated with IFN using bDNA
      probe assay which has lately been developed by Chiron corporation. Cases with
      complete response to IFN therapy showed 62% (49/79) in lower than 10(6) levels,
      27% (8/30) in 10(6)-10(7) and only 5% (2/41) in higher than 10(7). Genotype III,
      IV had higher response than type II on the same level of s-HCV RNA. These data
      indicates that determination of s-HCV levels by bDNA assay may be useful for
      prediction of the outcome of IFN therapy and making adequate schedule of the
      therapy in each cases.

PMID- 7521416
TI  - [Correlation between histological features of liver biopsy specimens and clinical
      effect of interferon on patients with chronic hepatitis C].
AB  - The correlation between histological features of liver biopsy specimens before
      interferon (IFN) treatment and the clinical effect of IFN administration on
      chronic hepatitis C was investigated. The changes in the biopsy specimens were
      graded on the basis of different histological features. The degree of portal
      fibrosis adversely affected the rate of normalization of ALT levels in the
      patients treated with IFN. During IFN treatment, the group of chronic hepatitis C
      patients who showed marked piecemeal necrosis and less lymphoid follicle
      formation in the liver specimens, showed abnormal ALT values even after
      disappearance of hepatitis C virus RNA in the sera, suggesting that functions of
      IFN other than antiviral effect, including enhancing interaction between
      lymphocytes and hepatocytes, sometimes induce exacerbation of hepatitis.

PMID- 7521415
TI  - [Prediction of the outcome of IFN therapy in type C chronic hepatitis from
      serological grouping of hepatitis C virus].
AB  - We investigated the relationship between serological grouping of hepatitis C
      virus and the response to IFN therapy in type C chronic hepatitis. In group I,
      responders were low (28%) with a high incidence of recurrence of HCV-RNA (72%).
      By contrast, in group II, responders were high (62%) and recurrence of HCV-RNA
      (17%) was low. Serological grouping of hepatitis C virus is useful in the
      prediction of the outcome of IFN therapy in type C chronic hepatitis.

PMID- 7521417
TI  - [The indication and the evaluation of IFN treatment of chronic hepatitis C].
AB  - The indication and the evaluation of IFN treatment for chronic hepatitis type C
      has been discussed. Good response to IFN depend on the level of HCV RNA just
      before the treatment. The patients who has low level of HCV RNA (less than 1
      Meq/ml by DNA probe assay) could be able to estimate the response more than 80%.
      On the contrary, it is less than 10% for the patients with high level of HCV RNA.
      The evaluation of IFN treatment for chronic hepatitis were divided into 3 groups.
      Cure was defined as the continuous normalization of serum ALT and disappearance
      of HCV RNA during 12 month or more after the treatment. Partial response was
      defined as continuous normalization of ALT level but positive for HCV RNA. The
      others were defined as non responder. First and second group should be evaluated
      for the IFN treatment. Final purpose for IFN treatment should be prevent to
      develop liver cirrhosis or hepatocellular carcinoma.

PMID- 7521419
TI  - [Sequential monitoring of various HCV-related markers in chronic hepatitis C with
      interferon treatment].
AB  - Interferon (IFN) which is a powerful antiviral cytokine is capable to cure
      approximately 40% of patients with chronic hepatitis C. We should like to know in
      detail whether IFN is operating enough to improve chronic hepatitis C during IFN
      treatment. Therefore it was evaluated what kind of HCV related markers were
      important to monitor the clinical course. We discussed HCV-RNA (RT-PCR, DNA probe
      assay) and some antibodies to HCV including our new IgM antibody to a HCV core
      peptide, cp14 (amino acid 5-40 of the core protein). HCV-RNA assayed by RT-PCR
      was considered best to monitor the therapeutic effect of IFN on chronic hepatitis
      C. However, as it is still not in general, IgM anti-cp14 might be an alternative
      in monitoring the response to IFN in patients with chronic hepatitis C.

PMID- 7521418
TI  - [Treatment of chronic hepatitis C with commercial available interferons].
AB  - Potential beneficial IFN treatment regimens were discussed based on the results
      of clinical trials conducted in Japan, with IFN alpha-2a, IFN alpha-2b,
      lymphoblastoid IFN, and IFN beta. With IFN alpha, 9 to 10 MIU daily for 2 to 4
      weeks, followed by three times a week for 20 to 22 weeks was considered the most
      effective treatment regimen in eradicating HCV. On the other hand, with IFN beta
      which is administered intravenously, 6 MIU daily for at least 8 weeks was
      considered necessary. However, it does not mean that the optimal treatment
      regimen has been identified. Further study is necessary to determine a more
      satisfactory IFN treatment for chronic hepatitis C with adequate monitoring of
      changes in serum HCV-RNA levels.

PMID- 7521420
TI  - [Significance of total dose of IFN in the treatment of chronic hepatitis C].
AB  - Two hundred thirteen patients with chronic hepatitis C were treated with IFN for
      4 to 52 weeks and complete response, in which ALT levels sustained within the
      normal value after more than 6 months following IFN treatment, was achieved in
      only 10% of the patients treated with less than 300 MU of IFN, whereas it was 42%
      in those treated with more than 500 MU, hence the total amount of IFN is
      important in the treatment of chronic hepatitis C. The duration of the treatment
      (4 to 52 weeks) made little difference in the response when more than 500 MU of
      IFN were administered.

PMID- 7521421
TI  - [Clinical study of retreatment of chronic hepatitis C with interferon (IFN) for
      non-complete responders on initial treatment].
AB  - From August 1990 to May 1993, we treated 23 non-complete responders on initial
      treatment with interferon and studied the factor which affects the effectiveness
      in the attempt to verify the factors for the selection of patients who are to
      receive it. Complete response was achieved in 8 (34.8%) patients, while the other
      15 patients did not achieve this degree of response. Three patients were of
      genotype II and 5 of genotype III in these 8 complete responders. All complete
      responders were patients with relapse who had had normalized serum ALT levels
      during the initial administration and undetectable HCV-RNA at the end of the
      period. No patient who failed to achieve normalization of the serum ALT level on
      initial treatment achieved a complete response on retreatment. HCV-RNA
      concentration before retreatment was significantly less than the one before
      initial treatment in 8 complete responders. Interferon retreatment of patients
      who do not achieve a complete response may be effective in relapsed cases with
      undetectable HCV-RNA at the end of initial treatment. Selection of patients to
      receive interferon retreatment requires careful review and consideration of
      genotype, HCV-RNA concentration, and the clinical response at initial treatment.

PMID- 7521422
TI  - [Serum HCV-RNA for evaluation of interferon-readministration to the former non
      responders in chronic hepatitis C].
AB  - We investigated the efficacy of retreatment with interferon in patients with
      chronic hepatitis C who were non responders to the initial interferon treatment.
      The results were as follows: 1) The effective rate was very low and 2 of the 16
      responded to the 2nd treatment. 2) Serum HCV-RNA levels before retreatment with
      interferon were compared among the 4 responders and the 13 non responders to
      interferon and it was significantly lower in the 4 responders. 3) HCV-genotypes
      may be useful to predict the efficacy of interferon readministration.

PMID- 7521424
TI  - [Effectiveness of interferon, glycyrrhizin combination therapy in patients with
      chronic hepatitis C].
AB  - SNMC (stronger Neominophagen C), whose active component is glycyrrhizin (a
      saponin extracted from licorice) has been utilized to improve the liver function
      in Japan. To assess the effectiveness of interferon (IFN), SNMC combination
      therapy in patients, who did not respond to IFN therapy alone, we investigate 28
      patients with histology of CAH 2B at 12 weeks after IFN administration. 15
      patients received IFN alone continuously (group A), and 13 patients received IFN
      with SNMC (group B) for 12 weeks thereafter. Normalization of serum ALT level was
      observed in 33.3% of group A and in 64.3% of group B. Disappearance of serum HVC
      RNA was 13.3% in group A and 38.5% in group B. But these data were not
      significant statistically. Histological improvement was not significant, between
      group A and B by Knodel's HAI score, but reversal of histological grade (Europe
      classification) was noted more frequently in group B. A case of posttransfusion
      hepatitis type C, exacerbated by IFN therapy is reported. HLA class I antigen was
      strongly expressed in the liver tissue after administration of IFN. In this case,
      potentiation of cellular immunity was thought to be the cause of the exacerbation
      and IFN, SNMC combination therapy was useful in improving liver function.

PMID- 7521423
TI  - [Study for relapse cases of chronic hepatitis C treated with interferon (IFN) and
      approach to more successful re-treatment of IFN].
AB  - It is well known that relapse of hepatitis develops in 30 approximately 40% cases
      of chronic hepatitis C after treatment of IFN. We assessed the background of
      those cases and investigated a scheme providing more successful re-treatment of
      IFN for those relapse cases. Cases developing complete response to re-treatment
      showed as follows. (1) During first IFN therapy, ALT sustained within normal. (2)
      Serum HCV-RNA levels before re-treatment demonstrated significantly lower than
      the levels of first therapy. (3) IFN dose of re-treatment was greater than first
      therapy. (4) Terms of initial daily IFN administration tended to be more longer
      (4W) than first therapy (2W).

PMID- 7521425
TI  - [Long-term prognosis after interferon therapy in chronic hepatitis type C].
AB  - 263 patients with chronic hepatitis C who received interferon therapy were
      followed up for an average 2.7 years after therapy. 36% of patients showed
      complete response, 16% of patients showed partial response, 48% of patients
      showed no response. 96 patients underwent liver biopsy after therapy and were
      observed long-term prognosis. 13 cases developed to liver cirrhosis.
      Histopathology before and after interferon, HCV-DNA probe before therapy were
      examined.

PMID- 7521426
TI  - [Examination in clinical course of HCV in interferon treatment].
AB  - We treated 812 patients who had chronic hepatitis C with interferon (IFN) and
      studied the effects of interferon. We defined complete response as normalization
      of amino-transferase more than 6 months after termination of IFN. Complete
      response by means of IFN therapy is dependent to some factors, that is HCV
      genotype, quantity of HCV-RNA, histology. Cases of HCV genotype III or IV, CH2A,
      less than 10(5) copy/ml of HCV-RNA are effective in treatment of IFN. On the
      other hand, cases of HCV genotype II, CH2B, more than 10(6) copy/ml of HCV-RNA
      are effective in treatment of IFN.

PMID- 7521427
TI  - [Long-term prognosis of the interferon-treated patients with chronic hepatitis C:
      compared with the natural course].
AB  - To evaluate the prognosis of the interferon (IFN)-treated patients with chronic
      hepatitis C (CH (C)), the clinical course and outcome of patients with CH (C) who
      were administered IFN more than 5 years before was compared with the natural
      course of untreated patients with CH (C) who were followed-up for 5 years. Good
      responders to IFN therapy showed normalized serum ALT level thereafter except one
      patient who were positive for serum HCV-RNA and had relapse of hepatitis.
      Histological improvements were observed in good responders. In groups of poor
      responders and non-responders, the fluctuation of serum ALT and histological
      changes after IFN therapy seemed to be similar to the natural course. Several
      problems on the prognosis are discussed.

PMID- 7521428
TI  - [Histological assessment of the liver long after interferon treatment in patients
      with chronic type C hepatitis].
AB  - The effects of interferon on chronic hepatitis C long after the treatments were
      assessed biochemically, virologically and histologically. Among the 12 cases who
      showed normal alanine aminotransferase (ALT) levels and seroconversion of HCV RNA
      after treatment, histological improvements were observed in 8. In contrast, among
      the 11 cases who showed abnormal ALT levels and HCV viremia after treatment,
      histological improvements were observed in only 1. Histological improvement of
      the liver was thus, well correlated with normalization of ALT levels and
      seroconversion of HCV RNA. These data indicate that complete histological
      resolution of chronic hepatitis C is obtainable by elimination of the virus by
      interferon treatment.

PMID- 7521430
TI  - [Evolution of hepatitis C virus (HCV) viremia and adaptation of HCV in persistent
      infection in patients with acute hepatitis].
AB  - HCV viremia had ceased in majority of patients with acute resolving hepatitis C,
      and it continued for at least 1 year in all patients with chronicity. The HCV RNA
      titer in serum decreased markedly after the onset of acute hepatitis and then re
      elevated in patients with chronicity. During this period, amino acid substitution
      rate in the E2/NS1 region (especially in HVR) was significantly higher in
      patients with acute hepatitis than in patients with chronic hepatitis. When
      patients with acute hepatitis C became persistent HCV carriers, the substitution
      rate decreased to the level seen in patients with chronic hepatitis. These
      observations suggest that rapid substitution of the amino acid sequence in the
      HVR of the E2/NS1 region may be one of the mechanisms of persistent HCV
      infection.

PMID- 7521429
TI  - [Interferon therapy for acute hepatitis C; changes in serum markers associated
      with HCV and clinical effects].
AB  - In order to prevent the progression to chronicity of acute hepatitis C, we
      treated 22 patients with natural human alpha or beta interferon (IFN) in varying
      doses (3-6 megaunit) daily, for 4 weeks everyday or TIW for 8 weeks. 14 (63.6%)
      of the 22 patients was cured with IFN therapy. According to the level of serum
      HCV RNA, 5 (83%) of the 6 patients with more than 10(5) copies/ml were progressed
      to chronicity, while 10 (91%) of the 11 patients with less than 10(5) copies/ml
      were cured. Curative rate on each genotypes was 3/9 (33%) in type II, 2/3 (67%)
      in type III and 1/2 (50%) in type IV. Positive cases for anti C100-3 before IFN
      were cured only 2 (28.6%) of the 7 patients, but negative cases were cured in 12
      (80%) of the 15 patients. This study reveal that IFN therapy for acute hepatitis
      C may contribute to prevent the progression to chronicity and that the
      determination of the level of serum HCV RNA, HCV genotypes and anti C 100-3
      levels may be useful to predict that efficacy of IFN and also to make a schedule
      for successful IFN therapy.

PMID- 7521431
TI  - [Interferon treatment of type C fulminant hepatitis].
AB  - On the contrary to Western countries, there are a substantial number of patients
      with type C fulminant hepatitis (FH) including coinfection on type A and type B
      hepatitis in Asian countries. The pathogenesis of FH is not fully understood,
      however, recent clinical observations suggest that enhanced host immune responses
      contribute to hepatocyte destruction in type C FH. In contrast to type B FH, type
      C FH is characterized by gradual and continuous liver necrosis probably duo to
      persistent infection of hepatitis C virus. Administration of interferon with
      immunosuppressive agents is the treatment of choice. Prognosis may be improved if
      the treatment is started in the early stage of the disease.

PMID- 7521432
TI  - [Autoimmune hepatitis with hepatitis C virus markers (anti HCV antibody or HCV
      RNA) and interferon therapy].
AB  - Autoimmune hepatitis (AIH) with hepatitis C virus (HCV) markers are seen
      frequently after the establishment of the method to detect HCV markers. According
      to the mechanism of the liver injury, we divide these cases of AIH with HCV
      markers to three groups; 1) the cases of AIH with HCV infection incidentally, 2)
      the cases of AIH triggered by HCV infection, and 3) the cases of chronic
      hepatitis C with immunological abnormalities. As far as we don't have any markers
      to differentiate these cases, we now think we should treat such cases with
      steroids at first before administering interferon, when we are not sure about the
      mechanism of the liver injury, because interferon is thought to be more risky
      than steroid for the cases who may have immunological abnormalities.

PMID- 7521433
TI  - [Effects of interferon treatment in alcoholic liver injury].
AB  - The concentration of Hepatitis C Virus (HCV) in the blood is increased by alcohol
      drinking and decreased by abstinence. These facts suggested that alcohol abuse
      may enhance the replication of HCV. The effects of alcohol on HCV replication may
      be related to increased development of chronic hepatitis to liver cirrhosis and
      hepatocellular carcinoma in HCV marker positive heavy drinker. These results
      indicated that HCV positive heavy drinkers must keep abstinence and that these
      patients have to be treated with interferon.

PMID- 7521434
TI  - [Long-term interferon (IFN), neominophagen C (SNMC) combination therapy of active
      liver cirrhosis type C].
AB  - Possible effects of IFN and SNMC combination therapy for active liver cirrhosis
      were described. 28 patients with active liver cirrhosis were treated with natural
      IFN alpha 3-6 MU TIW for 3-17 months (mean, 8 +/- 6). 8 of 28 patients received
      combination therapy of SNMC (40 ml iv, TIW). 8 (29%) of 28 patients sustained
      normal ALT levels with no relapse (complete response) which involved 6 patients
      with persistent lack of serum HCV RNA sequences after IFN therapy. In those 8
      patients, 4 had been received combination of SNMC. There were 4 (14%) patients
      with relative response. Patients with genotype III or IV had significantly higher
      response to IFN therapy than the patients with genotype II. In active liver
      cirrhosis, determination of HCV genotype and HCV RNA levels thought to be
      significant for the indication of IFN therapy, and that combination of SNMC may
      provide beneficial effect to IFN therapy for active liver cirrhosis.

PMID- 7521435
TI  - [Clinical analysis of patients with chronic hepatitis C who discontinued
      interferon treatment because of side effects--our experiences and recent
      reports].
AB  - We prospectively studied side effects about 54 patients with chronic hepatitis C
      treated with 3 to 10 MIU a day of interferon (IFN) alpha, which was administrated
      for 16 to 24 weeks. Every day, all of them wrote down every symptoms, by
      themselves, during its treatment. Any symptoms occurred in all patients and each
      incidence of symptoms such as fever, fatigue, headache, anorexia, arthalgia,
      myalgia, chill, itching, insomnia, nausea, numbness of hand and foot,
      irritability, diarrhea, eye ball pain, vomiting, were all higher than those which
      have been reported by some papers in Japan. So, it was considered that the
      symptom self-wrighting method by patient was useful to evaluate the entity of
      side effects. Furthermore, we studied 26 patients, who discontinued IFN treatment
      because of side effects and analyzed the background factors. Each incidence of
      symptoms of these patients were not always compatible to those incidences. But by
      observation of those symptoms, we could know severe side effects earlier.

PMID- 7521436
TI  - [Glucose intolerance during interferon therapy in patients with chronic hepatitis
      type C].
AB  - A new side effect of interferon (IFN) therapy, glucose intolerance was
      investigated using insulin-clamp study. In 75 g oral glucose tolerance tests
      before and after the IFN therapy showed no significant difference, whereas clamp
      study showed a significant decrease of glucose disposal. Our data suggested that
      insulin resistance was the main reason for glucose intolerance observed during
      INF therapy in the patients with chronic active hepatitis C. Early detection and
      strict control of glucose intolerance could avoid the progress of glucose
      intolerance.

PMID- 7521437
TI  - [Interstitial pneumonia induced by interferon therapy in type C hepatitis].
AB  - Interstitial pneumonia is known as one of the serious side effect of drugs.
      Recently, many investigators have reported that interstitial pneumonia (IP) which
      occurred during interferon (IFN) therapy for type C chronic hepatitis, and its
      appearance rate is considered to be more than 0.2% of patients who receive IFN.
      Though the mechanisms of IP during IFN therapy remains to be elucidated, one of
      the possible explanations is that excessive focal immune response in the lung
      derived from IFN might leads to the inflammation. For safe treatment, we must
      recognize that IFN induces IP during IFN therapy and give attention to its
      occurrence.

PMID- 7521438
TI  - [Cardiovascular complications of interferon therapy in chronic hepatitis C].
AB  - Severe cardiovascular complications (myocardial infarction, ventricular
      fibrillation et al.) have been reported in patients who have been administrated
      extremely high dose interferon (IFN) or cardio-toxic drugs, or who have had
      cardiovascular diseases. But cardiomyopathy, myocarditis and atrioventricular
      block were reported in patients who administered low dose IFN and no cardio-toxic
      drugs or had no cardiovascular diseases. We report here cardiovascular
      complications during IFN therapy for chronic hepatitis C. Cardiovascular
      complications that necessitated stopping IFN administration in 643 treated
      chronic hepatitis C patients are observed in 4 patients (0.62%). Second-degree
      atrioventricular block occurred in two patients, myocarditis in one patient and
      severe sinus bradycardia in one patient. So we have to check risk factors of
      cardiovascular complications before starting IFN therapy and electrocardiogram
      during IFN therapy.

PMID- 7521439
TI  - [Interferon-associated retinopathy].
AB  - During interferon (IFN) treatment for chronic hepatitis C, retinopathy develops
      in about one half of the patients. This "IFN-associated retinopathy" is
      characterized by cotton-wool spots (ischemic lesions) and superficial hemorrhage
      around the optic disc. It usually occurs 1 to 3 months after initiation of IFN
      therapy. Most of the patients with retinopathy have no symptoms, while some
      complain of impairment of visual acuity or flying specks. IFN-associated
      retinopathy tends to improve without any ophthalmic treatment and IFN therapy can
      be continued under careful observation. A complication of diabetes mellitus or a
      decrease in platelet count during IFN treatment may aggravate IFN-associated
      retinopathy. We emphasize that careful ophthalmologic follow-up is needed for all
      patients under IFN therapy.

PMID- 7521440
TI  - [Autoimmune disorders in interferon therapy].
AB  - Interferons (IFNs) have immunomodulatory properties such as direct increase in
      the production of pathogen autoantibodies, enhanced cytotoxic T cell and B cell
      activities, inhibition of T suppressor cell function and induction of HLA class I
      antigen expression. These actions of IFN induce autoimmune disorders including
      autoimmune thyroiditis, hemolytic anemia and thrombocytopenia, SLE, rheumatoid
      arthritis and psoriasis, however, these autoimmune diseases except for autoimmune
      thyroiditis, are rare among side effects of IFN therapy. Most of the patients
      showing these autoimmune disorders during IFN treatment have predisposal
      immunological abnormalities such as positive ANA and antithyroidal
      autoantibodies. We described here autoimmune disorders during and after IFN
      treatment among 1023 cases with chronic active type C hepatitis. The cases with
      SLE, thrombocytopenic purpura, rheumatoid arthritis and psoriasis showed good
      prognosis after cessation of IFN administration.

PMID- 7521441
TI  - [Anti-interferon antibody in chronic hepatitis C].
AB  - We studied anti-interferon (IFN) antibody in serial serum samples, obtained from
      34 patients with chronic hepatitis C treated with IFN (HLBI, recombinant IFN
      alpha 2a or-2b, HuIFN-beta). Anti-IFN antibody was measured by Western blotting,
      Anti-IFN antibody was detected in nine (8.1%) of the 111 samples. Two patients
      treated with recombinant IFN-alpha 2a developed neutralizing anti-IFN antibody,
      with the development of clinical resistance to IFN therapy, while none of 32
      patients treated with either HLBI, recombinant IFN-alpha 2b or HuIFN-beta
      developed anti-IFN antibody. Anti-IFN antibody was developed in one patients one
      month after IFN. It is believed that Western blotting, used in this study, is a
      useful method to evaluate the incidence and clinical significance of anti-IFN
      antibody.

PMID- 7521443
TI  - [Bladder carcinoma producing granulocyte colony stimulating factor (G-CSF). A
      case report].
AB  - A 69-year-old woman was admitted to the hospital complaining of general fatigue
      and lower abdominal pain. She had undergone total cystectomy because of invasive
      recurrent bladder carcinoma three months ago. Histopathological diagnosis was
      transitional cell carcinoma (TCC) grade 3 and squamous cell carcinoma (SCC),
      pT3a. A goose egg-sized painful mass was noticed at the lower abdominal region. A
      CT scan revealed an intrapelvic fist-sized mass and suggested tumor recurrence
      with ileus caused by intestinal invasion. The laboratory examination showed
      remarkable leukocytosis of 79,700/mm3 in the peripheral blood and serum analysis
      revealed high value of granulocyte colony stimulating factor (G-CSF), 240 pg/ml
      (normal: less than 30 pg/ml). In spite of active treatment, the patient died of
      cachexia about a month after detection of the leukocytosis. The autopsy showed
      that the recurrent tumor had positive immunohistochemical staining for G-CSF, and
      the bone marrow had reactive proliferation mainly by granulocytes. From these
      findings, this case was diagnosed as bladder carcinoma producting G-CSF. G-CSF
      producting tumor of the bladder is very rare. This was the 8th case in Japanese
      literatures. The previous reports were reviewed and discussed.

PMID- 7521442
TI  - Foot shock-induced changes in blood and brain serotonin and related substances in
      rats.
AB  - The effects of electric foot shock on peripheral and central serotonergic systems
      in rats have been studied. We have focused on the time course alterations with
      particular attention being paid to changes in 5-HT, 5-HIAA, tryptophan
      concentrations and 5-HIAA/5-HT ratios in blood and various parts of the brain,
      observed within 1 h following stress application. Blood and brain (7 regions)
      samples were taken immediately after electric foot shock, 30 min, 1 and 24 h
      later. In the blood stress induced a rise in tryptophan level as well as rises in
      5-HT, 5-HIAA levels and 5-HIAA/5-HT ratio within 1 h following stressful
      treatment. Tryptophan concentration was found to be increased in every part of
      the brain within 1 h after electric foot shock application. In striatum it
      remained higher even after 24 h. 5-HT level showed a significant rise only in
      medulla, while hypothalamus was the sole region where a fall in 5-HT was found.
      In other parts of the brain 5-HT level remained unaffected by stress. 5-HIAA
      content increased in almost every brain area studied except cerebellum and
      striatum. 5-HIAA/5-HT ratios shared the same pattern of changes. Briefly, foot
      shock altered 5-HT turnover in various brain regions, in particular within the
      first hour following stress application, whereas delayed response to stress was
      rarely observed. Increased brain tryptophan level seems to be necessary to cope
      with the enhanced 5-HT metabolism caused by stress, reflecting as a rise in 5
      HIAA concentration and 5-HIAA/5-HT ratio.

PMID- 7521444
TI  - Visualization of binding and uptake of oxidized low density lipoproteins by
      cultured mesangial cells.
AB  - BACKGROUND: It is hypothesized that oxidative modification of low density
      lipoprotein (LDL) in glomeruli may play an important role in the progression of
      initial glomerular injury to glomerulosclerosis. Recent biochemical studies have
      shown that cultured rat mesangial cells (RMC) express the scavenger receptors for
      oxidized LDL (Ox-LDL) suggesting that mesangial cells participate in the
      development of glomerulosclerosis through intracellular lipid loading. Yet it is
      not clear whether cultured human mesangial cells (HMC) also have receptors to
      take up Ox-LDL for foam cell formation. EXPERIMENTAL DESIGN: Colloidal gold or
      [125I]-labeled LDL was oxidized with copper ions. Binding experiments were
      performed by incubating the cultured human and rat mesangial cells at 4 degrees C
      with colloidal gold or [125I]-labeled Ox-LDL conjugates. The specificity of the
      [125I]-Ox-LDL binding was tested by competition experiments. Uptake and
      degradation studies were conducted by incubating the cells with labeled Ox-LDL at
      37 degrees C. RESULTS: When the cells were incubated with Ox-LDL-gold particles
      for 2 hours at 4 degrees C, gold particles associated with noncoated plasma
      membrane or coated pits were only found in RMC, but not in HMC. The binding of Ox
      LDL-gold to RMC was prevented by an excess of unlabeled Ox-LDL, polyinosinic acid
      or fucoidin. When the cells were incubated with increasing concentrations of
      [125I]-Ox-LDL, the specific binding of [125I]-Ox-LDL increased in both cells. The
      specific binding of [125I]-Ox-LDL (10 micrograms/ml) was 23% of the total binding
      for HMC and 47% for RMC, respectively. After incubation for 4 hours at 37 degrees
      C with Ox-LDL-gold conjugates only RMC, in particular, phagocytic mesangial cells
      exhibited extensive internalization of gold particles developing into foam cells.
      CONCLUSIONS: The results indicate that HMC have a small number of specific
      receptors for Ox-LDL and therefore a scavenger receptor-mediated pathway for Ox
      LDL was not visualized. In contrast, RMC, particularly phagocytic cells, express
      a large number of specific receptors for Ox-LDL generating foam cells.

PMID- 7521445
TI  - Inhibition of proliferation and induction of differentiation of pluripotent human
      embryonal carcinoma cells by osteogenic protein-1 (or bone morphogenetic protein
      7).
AB  - BACKGROUND: Osteogenic protein-1 (OP-1) is a member of the transforming growth
      factor-beta super family closely related to the bone morphogenetic proteins and
      also known as bone morphogenetic protein-7. Other members of this family of
      growth factors influence cell differentiation as well as cell growth in a number
      of systems. The Drosophila homolog encoded by the decapentaplegic locus is
      involved in dorsal-ventral pattern formation during embryogenesis, whereas the
      expression of several bone morphogenetic proteins including OP-1 is
      developmentally regulated in mammalian embryos. EXPERIMENTAL DESIGN: The effect
      of recombinant human OP-1 on the proliferation and differentiation of an
      established pluripotent human embryonal carcinoma (EC) cell line, NTERA2, and
      three nullipotent human EC cell lines, 2102Ep, 833KE and TERA-1, was
      investigated. These cells were grown under reduced serum conditions, and
      differentiation was monitored by morphology and expression of marker antigens.
      RESULTS: OP-1 inhibited proliferation of NTERA2 and induced their
      differentiation, marked by changes in cellular morphology, the loss of EC cell
      antigens (SSEA3, SSEA4, the liver isozyme of alkaline phosphatase), and the
      appearance of new antigens, notably SSEA1 and class 1 major histocompatibility
      complex antigens. These changes were irreversible and did not involve significant
      cell degeneration or cell death. The OP-1-induced differentiation of NTERA2
      appeared distinct from that induced by either retinoic acid or hexamethylene
      bisacetamide. Nevertheless, OP-1 did induce the homeobox gene, HOXA1. By
      contrast, OP-1 elicited only a limited and partial response from the nullipotent
      EC cell lines. CONCLUSIONS: Our results suggest that pluripotent human EC cells
      differentiate in response to OP-1 and that this factor can modulate the
      differentiation induced by retinoic acid. Like other members of the transforming
      growth factor-beta super family, OP-1 might play an inductive role in the early
      embryo. The results also suggest a possible therapeutic value for OP-1 in the
      treatment of some germ cell tumors.

PMID- 7521447
TI  - Angiogenesis and growth of isografted bone: quantitative in vivo assay in nude
      mice.
AB  - BACKGROUND: Understanding the regulation of vascularization and formation of bone
      after skeletal trauma is essential for the development of methods to promote
      healing. The lack of information on the biology of bone healing led us to
      establish an experimental model that facilitates the in vivo assessment of
      angiogenesis and growth of bone. EXPERIMENTAL DESIGN: Fresh, cryopreserved
      (frozen in the presence or absence of 10% dimethyl sulfoxide (DMSO)) or boiled
      neonatal femora were transplanted into dorsal skin fold chambers in adult mice of
      the identical strain, and angiogenesis and growth were monitored over 16 days.
      Computerized analysis of brightfield and epifluorescence images was employed to
      characterize the process of angiogenesis. Bone formation was quantified in vivo
      by the use of oxytetracycline. RESULTS: Reperfusion of pre-existing blood vessels
      of the graft was observed only in fresh transplanted femora, whereas femora of
      all experimental groups elicited angiogenic response from the host tissue. The
      rank order of the angiogenic response was: fresh > cryopreservation with DMSO >
      cryopreservation without DMSO > boiled. Growth of femora was completely abolished
      after cryopreservation or boiling. Only fresh transplanted femora increased in
      length (95 microns/day) and in cartilage diameter (41 microns/day). CONCLUSIONS:
      Our study demonstrates that (a) angiogenesis and growth of transplanted femora
      can be chronically assessed using in vivo microscopy; (b) the introduction of
      oxytetracycline for in vivo fluorescence microscopy allows the differential
      quantification of bone and cartilage growth; and (c) cryoprotection using DMSO
      enhances restoration of angiogenic potency after freezing. We consider this assay
      an excellent experimental model to study in vivo effects of agents or procedures
      that potentially modulate angiogenesis and growth of bone.

PMID- 7521448
TI  - An analysis of coupled multicomponent diffusion in interstitial tissue.
AB  - A one-dimensional multicomponent kinetic model was developed to simulate the
      interstitial diffusion of macromolecules in a three component system, consisting
      of water, the macromolecule and the interstitial matrix. Movement of the
      individual components was modeled as occurring in finite jumps between discrete
      low energy wells along paths defined in terms of species occupation. The flow
      rate was expressed as a function of the local species concentration, the jump
      distance, and a kinetic frequency parameter. The model, implemented in pseudo
      bond graph form, was examined by fitting it to data obtained for the transport of
      fluorescein tagged dextran to determine the kinetic constants for that specific
      system.

PMID- 7521446
TI  - Paracrine interactions between fibroblasts and endothelial cells in a serum-free
      coculture model. Modulation of angiogenesis and collagen gel contraction.
AB  - BACKGROUND: Previous data suggest that paracrine interactions between fibroblasts
      and endothelial cells modulate the formation of granulation tissue during wound
      healing. The study of these interactions in vivo is hindered by the interference
      of serum and other cell types. To overcome this limitation, we developed a serum
      free in vitro model in which microvessels were cocultured with fibroblasts in a 3
      dimensional collagen gel. EXPERIMENTAL DESIGN: Microvascular networks were
      obtained by culturing rat aortic endothelial cells between two layers of
      collagen. Microvessels were cultured in serum-free medium with or without
      fibroblasts embedded in the collagen. The cultures were studied by phase contrast
      microscopy, conventional electron microscopy, and by light and electron
      immunohistochemistry. The role of endothelial cells and the endothelial-derived
      peptide endothelin-1 in the transformation of fibroblasts into myofibroblasts was
      studied by evaluating fibroblast alpha-smooth muscle actin expression and
      collagen contraction. The angiogenic properties of fibroblasts were investigated
      with the rat aorta assay. RESULTS: Microvessels cultured without fibroblasts
      degenerated within 3 to 4 days. Fibroblasts stabilized the microvessels greatly
      prolonging their life span. This effect was associated with an increased
      deposition of subendothelial extracellular matrix. Both fibroblasts and
      fibroblast-conditioned medium stimulated angiogenesis in the rat aorta assay.
      Endothelial cells and endothelin-1 enhanced the expression of alpha-smooth muscle
      actin in fibroblasts and stimulated fibroblast-mediated collagen contraction.
      CONCLUSIONS: This study demonstrates that endothelial-fibroblast interactions can
      be studied in vitro under serum-free conditions. Our results suggest that
      paracrine mechanisms operating between endothelial cells and fibroblasts play a
      key role in the formation and contraction of granulation tissue during wound
      healing. We propose that fibroblasts stimulate angiogenesis and stabilize the
      neovascular endothelium which in turn promotes the morphological and functional
      transformation of fibroblasts into myofibroblasts.

PMID- 7521449
TI  - Beta-adrenoceptor subtypes in the atrioventricular conducting system and
      myocardium of spontaneously hypertensive rats: effects of angiotensin-converting
      enzyme inhibition by perindopril.
AB  - Quantitative autoradiography was used to determine the density and distribution
      of beta 1- and beta 2-adrenoceptors in the atrioventricular (AV) conducting
      system and surrounding myocardium of spontaneously hypertensive rats (SHR) after
      chronic infusion of perindopril (1 mg/kg/day) for 14 days by osmotic mini-pumps.
      Systolic blood pressure (SBP) was measured for a period of 4 weeks (2 weeks
      before and 2 weeks during perindopril infusion) in control and treated animals.
      Animals infused with vehicle (water) had a mean SBP of 248 mm Hg (measured on day
      29); animals treated with perindopril had lower SBP (121 mm Hg, day 29).
      Perindopril treatment also prevented development of cardiac hypertrophy in SHR.
      beta-Adrenoceptor densities were measured in the AV node, His bundle, left and
      right bundle branches (LB, BB), interventricular and interatrial septa (IVS,
      IAS), mitral valve (MV), right papillary muscle, left and right ventricles (LV,
      RV), left and right atria (LA, RA), and apex. Perindopril produced no significant
      change in beta-adrenoceptors in any cardiac region examined. The results suggest
      that under experimental conditions in which perindopril treatment prevented
      cardiac hypertrophy and decreased SBP, there was no significant interaction
      between the renin-angiotensin system (RAS) and beta-adrenoceptor system in rat
      heart.

PMID- 7521450
TI  - Dopamine-dependent diastolic dysfunction in moderate hypothermia.
AB  - We designed an experimental animal study to study the effects of dopamine (DA) on
      diastolic function in hypothermia. DA was applied at five incremental infusion
      rates in 6 sheep during normothermia and moderate hypothermia (29 degrees C).
      Left ventricular end-diastolic pressure (LVEDP) was increased during hypothermia
      as compared with normothermia at all doses of DA. Contraction and relaxation
      velocity were changed only slightly during hypothermia; during normothermia, both
      velocities were markedly increased. The pronounced hemodynamic effect observed
      during hypothermia was further intensified by occurrence of aftercontractions,
      which disappeared at very high DA doses. These paradoxic results were considered
      the result of hypothermia-induced reduction in active transport mechanisms
      responsible for regulation of the cytoplasmic CA2+ concentration. The generally
      reduced inotropic effect of DA, the risk of paradoxic reactions, and the
      occurrence of aftercontractions must be taken into account when emergency drugs
      are administered clinically during hypothermia.

PMID- 7521452
TI  - Analysis of P2-purinoceptor subtypes on the smooth muscle and endothelium of
      rabbit coronary artery.
AB  - We studied purinoceptor subtypes mediating constriction and dilatation in
      isolated rabbit coronary arteries with and without endothelium by comparing the
      effects of adenosine, ATP and the ATP analogues, alpha, beta-methylene ATP and 2
      methylthio ATP. For contraction, the rank order of agonist potency was alpha,
      beta-methylene ATP > 2-methylthio ATP >> ATP; adenosine did not produce
      contraction. Removal of the endothelium did not affect these responses, but they
      were abolished by previous desensitisation with alpha, beta-methylene ATP. For
      relaxation, adenosine, ATP, and 2-methylthio ATP were equipotent, but alpha, beta
      methylene ATP had no vasodilator effect and caused further contraction of the
      preparations. A transient contraction often preceded the relaxations to ATP at
      higher concentrations. The dilator responses to adenosine, ATP, and 2-methylthio
      ATP were significantly reduced but not abolished in preparations denuded of
      endothelium; previous desensitisation with alpha, beta-methylene ATP had no
      effect on the relaxant responses but abolished the initial transient contractions
      to ATP and 2-methylthio ATP. These results indicate the presence of vasodilator
      P1- and P2Y-purinoceptors on smooth muscle and, to a lesser extent, on
      endothelium and P2X-purinoceptors, mediating transient vasoconstriction on smooth
      muscle alone. The presence of smooth muscle P2Y-purinoceptors is unusual and has
      functional implications regarding the nature of the response of the coronary
      artery to ATP.

PMID- 7521451
TI  - Hemodynamic and humoral effects of chronic treatment with the neutral
      endopeptidase inhibitor SCH 42495 in spontaneously hypertensive rats.
AB  - Blockade of atrial natriuretic factor (ANF) degradation by specific neutral
      endopeptidase (NEP) inhibitors may be useful in treatment of hypertension because
      of the potential diuretic, natriuretic, and arterial pressure (AP)-lowering
      effects. To test this possibility, we examined the effects of chronic oral
      treatment with the NEP inhibitor SCH 42495 on BP, diuresis, natriuresis, plasma
      ANF, cyclic GMP, and the renin-angiotensin system (RAS) in conscious unrestrained
      spontaneously hypertensive rats (SHR) and compared them with the effects induced
      by the angiotensin-converting enzyme (ACE) inhibitor spirapril (SPIR). Four
      groups of adult SHR were treated orally for 4 weeks with placebo, SCH 42495 3
      mg/kg twice daily (b.i.d.), SCH 42495 30 mg/kg b.i.d., and spirapril 1 mg/kg
      b.i.d. Systolic BP (SBP) was measured weekly, and 24-h urine was collected every
      week for measurement of urinary volume, sodium, potassium, and cyclic GMP
      excretion. Plasma ANF, cyclic GMP, renin activity (PRA), and aldosterone (ALDO)
      were determined from blood collected when the rats were killed. After 4-week
      treatment with SCH 42495, circulating levels of ANF were similar in both SCH
      42495- and placebo-treated SHR; plasma cyclic GMP was higher, however, in the
      treated rats than in controls and urinary cyclic GMP increased only with the
      higher dose of SCH 42495. PRA and plasma ALDO tended to be lower in both SCH
      42495-treated groups than in controls, yet BP, diuresis, and natriuresis
      throughout the study were not different from controls. In contrast, spirapril
      decreased BP; this effect was associated with significant increments in renin and
      decrements in ALDO and ANF, without changes in plasma and urinary cyclic
      GMP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521453
TI  - Effects of berberine on delayed afterdepolarizations in ventricular muscles in
      vitro and in vivo.
AB  - The effects of berberine on delayed afterdepolarizations in ventricular muscles
      in vitro and in vivo were investigated to help explain the mechanisms for its
      antiarrhythmic action. Berberine 3 mumol reduced the amplitude of delayed
      afterdepolarizations induced by ouabain or posthypoxic reoxygenation and
      abolished subsequent triggered activity in isolated guinea pig right ventricular
      papillary muscles. At 30 mumol, it decreased the incidence of delayed
      afterdepolarizations, associated with a further decrease in the amplitude of
      delayed afterdepolarizations. In rabbit left ventricular (LV) muscles in vivo,
      berberine 1 mg/kg intravenously (i.v.) decreased the amplitude of delayed
      afterdepolarizations evoked by ouabain and calcium gluconate from 9.6 +/- 1.9 to
      6.8 +/- 0.8 mV and left stellate ganglion stimulation from 9.4 +/- 2.1 to 6.2 +/-
      0.7 mV and blocked ventricular arrhythmias. After a 4-mg/kg i.v. bolus, the drug
      inhibited and even completely abolished development of delayed
      afterdepolarizations, yet still reduced maximal velocity of depolarization in
      isolated and in vivo ventricular muscles. Therefore, one of the important
      mechanisms for antiarrhythmic action of berberine may be suppression of delayed
      afterdepolarizations, which may be attributable in part to a decrease in Na+
      influx.

PMID- 7521454
TI  - Effects of a novel cardiotonic agent (+-)-6-[3-(3,4-dimethoxybenzylamino)-2
      hydroxypropoxy]-2(1H)-quinolino ne (OPC-18790) on contractile force, cyclic AMP
      level, and aequorin light transients in dog ventricular myocardium.
AB  - We studied the effects of a novel cardiotonic agent OPC-18790 [(+-)-6-[3-(3,4
      dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)- quinolinone] on isometric
      contractions, intracellular aequorin light transients, and cyclic AMP levels in
      isolated dog ventricular trabeculae. The positive inotropic effect (PIE) of OPC
      18790 (1-30 microM) was consistently associated with an abbreviation of
      contractions and an increase in the amplitude of aequorin light transients. The
      maximum responses of Ca2+ transients and force to OPC-18790 were approximately
      40% of the isoproterenol-induced maximum. Carbachol (3 microM) markedly
      attenuated the increases in force, light transients, and cyclic AMP accumulation
      induced by OPC-18790. These results indicate that OPC-18790 is a cardiotonic
      agent with moderate effectiveness, and that the PIE of OPC-18790 may be produced
      mainly by an increase in intracellular Ca2+ transients induced by cyclic AMP
      accumulation. For a given increase in amplitude of Ca2+ transients, OPC-18790
      produced a more pronounced increase in force of contraction (FOC) than did
      isoproterenol, suggesting that OPC-18790 does not produce as great a decrease in
      Ca2+ sensitivity of contractile proteins as does isoproterenol. These
      observations indicate that among cardiotonic agents acting through cyclic AMP
      pathway, regulation of contractility produced by the selective cyclic AMP
      phosphodiesterase III (PDE-III) inhibitor OPC-18790 is qualitatively different
      from the regulation induced by isoproterenol that acts on cyclic AMP generation
      in intact myocardial cells.

PMID- 7521455
TI  - Allosteric interaction of semotiadil fumarate, a novel benzothiazine, with 1,4
      dihydropyridines, phenylalkylamines, and 1,5-benzothiazepines at the Ca(2+)
      channel antagonist binding sites in canine skeletal muscle membranes.
AB  - We assessed the binding characteristics of a benzothiazine Ca(2+)-channel
      antagonist, semotiadil, in canine skeletal muscle membranes. Semotiadil inhibited
      binding of (+)-[3H]PN 200-110 (maximum inhibition 80%), and almost completely
      inhibited binding of both (-)-[3H]desmethoxyverapamil and D-cis-[3H]diltiazem to
      their specific binding sites with an IC50 value of 0.2-2 microM and a Hill slope
      of 0.6-0.9. Saturation isotherm and dissociation kinetic studies suggest that
      semotiadil acts as a noncompetitive inhibitor at the 1,4-dihydropyridine,
      phenylalkylamine, and benzothiazepine (BTZ) recognition sites in the L-type Ca2+
      channel: (a) Scatchard analysis showed that semotiadil decreased maximum binding
      (Bmax) of the three classes of Ca2+ channel antagonists, while causing a slight
      increase in the equilibrium dissociation constant (Kd) in the case of (+)-[3H]PN
      200-110 binding or no significant change in Kd values for binding of (-)
      [3H]desmethoxyverapamil and D-cis-[3H]diltiazem to their specific binding sites;
      and (b) dissociation kinetics of the (+)-[3H]PN 200-110 and D-cis-[3H]diltiazem
      bindings were accelerated by semotiadil. These results suggest that semotiadil
      has a strong negative allosteric interaction with three classes of Ca2+ channel
      antagonists, including 1,4-dihydropyridines, phenylalkylamines, and BTZ at their
      specific binding sites.

PMID- 7521456
TI  - Hemodynamic performance during exercise in patients with severe chronic
      congestive heart failure before and after a single dose of pimobendan.
AB  - Duration of symptom-limited exercise on a bicycle ergometer (constant workload of
      25 W) was determined in 12 patients with severe chronic congestive heart failure
      (CHF) due to dilated cardiomyopathy (CMP, 4 patients) or ischemic heart disease
      (IHD, 8 patients) undergoing hemodynamic monitoring. Mean exercise duration was
      214 +/- 124 s and produced severe dyspnea lasting > 5 min in all patients. The
      next morning, each patient exercised again to the same level; pimobendan (10 mg
      orally) was then administered, and exercise to the same workload was repeated 4
      and 10 h later. Mean +/- SD exercise-induced changes in heart rate (HR, min-1),
      pulmonary capillary wedge pressure (PCW, mm Hg), cardiac output (CO, L/min-1),
      and stroke volume index (SVI, ml.min-1) were as follows. At baseline, HR was 85
      +/- 17-110 +/- 21 beats/min (p < 0.001), PCW 21 +/- 10-31 +/- 10 mm Hg (p <
      0.05), CO 3.7 +/- 1.0-3.9 +/- 1.0 L.min-1 (NS), and SVI, 25 +/- 7-20 +/- 7 ml.m-2
      (NS). Four hours after pimobendan administration, HR was 90 +/- 14-113 +/- 21
      beats/min (p < 0.001), PCW 11 +/- 7-20 +/- 10 mm Hg (p < 0.05), CO 5.3 +/- 0.7
      5.8 +/- 1.0 L.min-1 (NS), and SVI 33 +/- 3-29 +/- 7 ml.m-2 (NS).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7521457
TI  - Pharmacologic differentiation between endothelium-dependent relaxations sensitive
      and resistant to nitro-L-arginine in coronary arteries.
AB  - We investigated whether formation of endothelium-derived relaxing factor (EDRF)
      and endothelium-derived hyperpolarizing factor (EDHF) in porcine and bovine
      endothelial cells (PAECs) was stimulated by different kinin receptors and studied
      pharmacologic differences and similarities between the two types of bradykinin
      induced relaxation of bovine or porcine coronary arteries. Cultured PAECs were
      used for [3H]bradykinin binding assay and for measurement of the endothelial free
      [Ca2+]i by the fura-2/AM method. In organ bath studies with strips of bovine and
      porcine coronary arteries (endothelium intact), changes in length were recorded
      and cyclic GMP was measured by radioimmunoassay (RIA). Two bradykinin binding
      sites were detected, suggesting the presence of two subtypes of B2 kinin
      receptors. Bradykinin increased [Ca2+]i, and this action was antagonized by the
      B2 kinin receptor antagonist Hoe 140 and the K channel inhibitor
      tetrabutylammonium (TBA). Hoe 140 competitively antagonized the relaxing effects
      of bradykinin, whereas a B1 antagonist was inactive. L-omega N-nitro-arginine (L
      NNA) diminished one part of bradykinin-induced relaxation and abolished the
      increases in cyclic GMP; TBA inhibited another part of the relaxing effect and
      attenuated (but not significantly) increases in cyclic GMP, and Hoe 140
      completely inhibited relaxation and increases in cyclic GMP. The results indicate
      that the bradykinin response is mediated by biosynthesis of EDRF, which is
      sensitive to L-NNA, and of EDHF, which is sensitive to TBA.

PMID- 7521458
TI  - Differential effects of ATP- and 2-methylthioATP-induced relaxation in guinea pig
      coronary vasculature.
AB  - The Langendorff heart preparation was used to investigate the mechanism of action
      of vasodilatation evoked by ATP and its analogues in guinea pig coronary
      vasculature. The relative order of potency of ATP and its analogues in causing a
      reduction in perfusion pressure was 2-methylthioATP (2-meSATP) > ATP > beta,
      gamma-methyleneATP (beta,gamma-meATP) > or = alpha,beta-methyleneATP (alpha,beta
      meATP), thus establishing the presence of P2y-purinoceptors in this preparation.
      L-NG-nitroarginine methyl ester (L-NAME, 3 x 10(-5) M) significantly attenuated
      both the area under the flow-time curve and the maximum decrease in perfusion
      pressure of the vasodilatation produced in response to 2-meSATP (5 x 10(-12)-5 x
      10(-9) mol). However, for ATP (5 x 10(-7)-5 x 10(-10) mol), L-NAME 3 x 10(-5) M
      significantly attenuated the area under the flow-time curve of the response but
      did not reduce the maximum decrease in perfusion pressure except at one low dose
      (5 x 10(-10) mol). L-Arginine 1.5 x 10(-3) M significantly reversed inhibition of
      the area under the flow-time curve of the response to 2-meSATP 5 x 10(-10) mol
      and ATP 5 x 10(-8) mol by L-NAME 3 x 10(-5) M. The maximum decrease in perfusion
      pressure of the response to ATP 5 x 10(-10)-5 x 10(-7) mol was significantly
      attenuated in the presence of indomethacin 10(-6) M.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7521459
TI  - Endogenous vasoactive systems and the pressor effect of acute N omega-nitro-L
      arginine methyl ester administration.
AB  - The contribution of the renin-angiotensin system (RAS) and various endogenous
      vasoconstrictors on the pressor response to acute N omega-nitro-L-arginine methyl
      ester (L-NAME) administration (200 micrograms/kg/min) was assessed in
      anesthetized Wistar rats. Activity of the endogenous RAS was suppressed either by
      chronic treatment by a nonpeptide angiotensin II (AII) receptor antagonist
      (losartan) or an angiotensin-converting enzyme inhibitor (ACEI: enalapril), DOCA
      salt pretreatment (without previous uninephrectomy), and binephrectomy (36-40
      hours before experiments). We also studied the influence of chronic dietary
      sodium restriction. The role of alpha 1-adrenoceptor activity, endothelin (ET),
      and eicosanoids was evaluated in rats pretreated by prazosin, phosphoramidon (a
      nonspecific blocker of the conversion of big ET to ET), indomethacin, and the
      thromboxane A2 (TXA2) prostaglandin H2 (PGH2)-receptor antagonist SQ 29548,
      respectively. Finally, we tested the influence of the calcium channel blocker
      nicardipine on the vasopressor effect of L-NAME. In nonpretreated animals, L-NAME
      infusion induced an increase in mean arterial pressure (MAP) of 38 +/- 4 mm Hg.
      Chronic suppression of the RAS by losartan, enalapril, or DOCA did not alter the
      response to L-NAME, but the effect of L-NAME was moderately blunted in
      binephrectomized rats. Moderate attenuation (approximately 25%) and to a similar
      extent of the pressor effect of L-NAME was afforded by the low-sodium diet,
      phosphoramidon, SQ 29548, and indomethacin, whereas nicardipine markedly blunted
      by 74% the effect of L-NAME. We conclude that the acute pressor effect of L-NAME
      is mediated (at least in part) by cyclooxygenase-dependent products (mainly TXA2)
      and ET, but not by the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521460
TI  - Novel organic nitrates are potent dilators of large coronary arteries with
      reduced development of tolerance during long-term infusion in dogs: role of the
      sulfhydryl moiety.
AB  - The vasodilator action of organic nitrates can be severely impaired by induction
      of drug tolerance. A critical depletion of sulfhydryl groups has been proposed to
      play a key role in impairment of the biotransformation of organic nitrates to
      nitric oxide (NO). We studied the effects of the new cysteine-containing nitrate
      SPM-5185 and the corresponding cysteine-free compound SPM-4744 on hemodynamics
      and large coronary artery dilation in chronically instrumented conscious dogs.
      Both nitrates caused dose-dependent increases of the diameter of the left
      circumflex artery (LCX); the cysteine-containing compound SPM-5185 however,
      caused such increases at < or = 30-fold lower doses as compared with SPM-4744.
      Coinfusion of the cysteine-containing analogue of SPM-5185 lacking the nitrate
      group (SPM-5267) did not alter the dose-response relationship to SPM-4744.
      Continuous infusion of SPM-5185 (4 micrograms/kg/min, n = 6) and SPM-4744 (2.7
      micrograms/kg/min, n = 5) elicited LCX diameter increases of 0.24 +/- 0.06 and
      0.17 +/- 0.07 mm, respectively, representing 60-70% of maximal dilator capacity.
      In contrast to classic organic nitrates, both SPM-5185 and SPM-4744 caused LCX
      diameter to decrease only slightly during 5-day infusions. Both compounds
      elicited sustained dilation even at day 5 (p < or = 0.05). SPM-5185 caused an
      initial decrease in mean arterial pressure (MAP) and evoked sustained increases
      in heart rate (HR), whereas SPM-4744 had no significant peripheral effects. On
      withdrawal of SPM-5185, LCX diameter was decreased below pretreatment values for
      several hours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521461
TI  - Effect of calcium channel blockers on the growth of human vascular smooth muscle
      cells derived from saphenous vein and vascular graft stenoses.
AB  - Vascular restenosis after invasive interventions is an important clinical problem
      for which no preventive pharmacologic therapy exists. Calcium channel blockers
      have been shown to inhibit myointimal hyperplasia in animal models of restenosis
      and in some small and flawed clinical coronary restenosis trials. We examined the
      inhibitory effect of amlodipine, verapamil, and diltiazem on the growth of
      cultured human vascular smooth muscle cells (VSMC) derived from saphenous vein (n
      = 20) and graft stenoses (n = 7), in 14-day proliferation assays and [methyl
      3H]thymidine uptake studies. Amlodipine and verapamil produced significant
      inhibition (30%) of VSMC proliferation and DNA synthesis at 10 microM but not at
      500 nM-1 microM. To our knowledge, this is the first study to examine the
      antiproliferative effect of calcium channel blockers in VSMC derived from human
      graft stenoses. Growth inhibition of VSMC from graft stenoses was not
      significantly different from that of control saphenous vein-derived cells. We
      conclude, therefore, that calcium channel blockers inhibit human VSMC
      proliferation in vitro, regardless of whether the cells were grown from graft
      stenoses or saphenous vein. However, the concentrations at which these calcium
      channel blockers elicit antiproliferative effects may not be attainable during
      therapeutic dosing in humans.

PMID- 7521464
TI  - Effects of halothane and ketamine on activation and inactivation of myocardial
      calcium current.
AB  - We evaluated the effects of clinically relevant concentrations of halothane (1%)
      and ketamine (10(-4) M) on activation, inactivation, and recovery from
      inactivation of voltage-gated sarcolemmal calcium current (ICa) in single guinea
      pig ventricular myocytes, using the whole cell voltage clamp. Both anesthetics
      had qualitatively similar effects. The potential at half-activation was shifted
      from -18 to -23 mV for halothane (p < 0.03) and from -17 to -21 mV for ketamine
      (p = 0.005). There was no change in the slope of the activation curve for either
      anesthetic. The potential at half-inactivation was shifted from -29 to -40 mV
      with exposure to halothane (p < 0.001) and from -27 to -33 mV (p < 0.001) with
      exposure to ketamine. There was no change in the slope of the inactivation curve
      with either agent. The changes in time constant of recovery from steady-state
      inactivation with halothane did not reach statistical significance (178 vs. 207
      ms, p = 0.20) and was significantly prolonged with exposure to ketamine (106 vs.
      157 ms, p = 0.005). The two anesthetics show parallel shifts in activation,
      inactivation, and recovery from inactivation of ICa in ventricular myocardial
      cells. These findings in normal ventricular myocytes may help interpret the
      interactions of these anesthetics with other types of heart muscle, such as
      ischemic and immature myocardium.

PMID- 7521462
TI  - Dihydropyridine Ca2+ channel agonists and antagonists potentiate ultraviolet
      light-induced relaxation through cyclic GMP formation in porcine coronary artery.
AB  - We investigated the mechanisms of dihydropyridine Ca2+ channel agonist
      potentiation of ultraviolet (UV) light-induced smooth muscle relaxation in
      porcine coronary artery rings. Rings contracted with the dihydropyridine Ca2+
      channel agonist, (+)-S-202-791, were more sensitive to relaxation in response to
      UV light than were rings contracted with KCl or histamine. Relaxation of (+)-S
      202-791-contracted rings was independent of the presence of endothelium and was
      associated with cyclic GMP formation. Methylene blue (MB) prevented UV light
      induced relaxation and cyclic GMP formation. UV light-induced relaxation of
      histamine and KCl contracted rings and cyclic GMP formation were potentiated by
      (+)-S-202-791 or the Ca2+ channel antagonist, (-)-R-202-791. Exposure of (+)-S
      202-791 to UV light decreased its contractile potency. The data suggest that UV
      light-induced relaxation of vascular smooth muscle (VSM) is mediated through
      cyclic GMP formation and that potentiation of UV light-induced relaxation by
      dihydropyridine Ca2+ channel agonists results from their breakdown to a
      compound(s) that activates guanylate cyclase.

PMID- 7521466
TI  - Verapamil has antiarrhythmic effects that are mediated in brain through
      endogenous opioids.
AB  - The purpose of this study was to examine the hypothesis that the calcium channel
      blocker verapamil modulates catecholamine-induced arrhythmias in brain and to
      explore potential mechanisms of action. Wistar rats with catheters previously
      inserted in the lateral cerebral ventricle and femoral artery received verapamil
      10 or 50 micrograms/kg or the diluent (intracerebroventricularly, i.c.v.) into
      the lateral cerebral ventricle. Epinephrine was infused to produce arrhythmias.
      Onset of ventricular arrhythmias, premature ventricular complexes (PVCs),
      occurred at a significantly (p < 0.05) higher epinephrine dose after the higher
      dose of verapamil. Development of fatal arrhythmias, mainly ventricular
      tachyarrhythmias, occurred at significantly (p < 0.05) higher epinephrine
      concentrations with verapamil 50 micrograms/kg i.c.v. as compared with controls.
      Comparison of the two enantiomers of verapamil (50 micrograms/kg i.c.v.) showed
      that S(-)verapamil had the same effect as the racemic mixture whereas
      R(+)verapamil was intermediate between the control and S(-)verapamil. The
      antiarrhythmic action of verapamil could not be explained by alteration of the
      blood pressure (BP) response to epinephrine. Endogenous opioids were implicated
      in this action of verapamil because the (-)enantiomer of naloxone, which is an
      opioid antagonist, significantly (p < 0.05) antagonized the antiarrhythmic
      effects of centrally administered verapamil to suppress epinephrine-induced
      arrhythmias. In contrast the (+)enantiomer of naloxone did not alter verapamil
      induced increase in arrhythmia threshold. Pretreatment with pertussis toxin
      i.c.v. antagonized the effects of verapamil. Verapamil did not alter the cyclic
      AMP response to isoproterenol in lymphocytes isolated from Wistar rats not
      exposed to any other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521463
TI  - Assessment of flosequinan's direct effect on human arterial, venous, and cardiac
      muscle: comparison with other classes of agents used to treat heart failure.
AB  - We wished to provide comparative information regarding the direct effects of
      flosequinan, a novel quinolone under development for treating heart failure, on
      isolated human arterial, venous, and cardiac muscle. A similar assessment was
      made for four other agents--milrinone, ouabain, captopril and diltiazem--that
      have been used to treat heart failure patients, as well as for flosequinoxan,
      which is the primary metabolite of flosequinan. Flosequinan produced a potent and
      balanced relaxant effect on norepinephrine (NE)-contracted human arterial and
      venous smooth muscle, with IC25 values of 0.32 and 0.50 microM, respectively. At
      higher concentrations, flosequinan also produced a positive inotropic effect on
      human cardiac muscle (EC25 = 32 microM). A similar pattern of responses was
      observed with flosequinoxan. The pharmacologic profile obtained for the other
      agents examined differed from that observed with flosequinan and flosequinoxan in
      the following ways: Milrinone produced both vascular relaxant and positive
      inotropic effects, but at comparable concentrations; ouabain produced both
      vasoconstrictor and positive inotropic effects; diltiazem exerted a vascular
      relaxant effect at low concentrations and a negative inotropic effect at higher
      concentrations; and captopril had slight arterial relaxant and negative inotropic
      effects. These results demonstrate that the pharmacologic profile of flosequinan
      and flosequinoxan is unique as compared with that of other agents that have been
      used to treat patients with heart failure.

PMID- 7521465
TI  - HA1004, an intracellular calcium antagonist, selectively attenuates pulmonary
      hypertension in newborn lambs.
AB  - HA1004, an isoquinolinesulfonamide and a cyclic nucleotide-dependent protein
      kinase inhibitor, is an intracellular calcium antagonist that produces vascular
      smooth muscle (VSM) relaxation in vitro. We studied the hemodynamic effects of
      intravenous (i.v.) infusions of HA1004 (0.1-2.0 mg/kg) in vivo in 8 newborn
      lambs, at rest and during pulmonary hypertension induced either by the i.v.
      infusion of U46619, a thromboxane A2 (TXA2) mimic, or by alveolar hypoxia. For
      comparison, we also studied the hemodynamic effects of i.v. infusions of
      nifedipine (15 and 40 micrograms/kg/min), a calcium entry blocker. At rest,
      HA1004 produced slight but significant changes in pulmonary and systemic arterial
      pressure (PAP, SAP) and pulmonary and systemic vascular resistances (PVR, SVR) (p
      < 0.05). During pulmonary hypertension induced by U46619, HA1004 decreased PAP 12
      23% and PVR 9-33% (p < 0.05), whereas SAP decreased 7% and SVR decreased 14% at
      only one dose (p < 0.05). During pulmonary hypertension induced by alveolar
      hypoxia, HA1004 decreased PAP 6-32% and PVR 11-30% (p < 0.05), whereas SAP
      decreased 15% only at the highest dose (p < 0.05). Linear regression analysis of
      the pooled data demonstrated that HA1004 caused selective pulmonary vasodilation
      during pulmonary hypertension. Nifedipine decreased PAP 6 and 14% and SAP 5 and
      17% during pulmonary hypertension. In newborn lambs with pulmonary hypertension,
      HA1004, an intracellular calcium antagonist, is more selective and potent than
      nifedipine, a calcium entry blocker, in decreasing PAP and therefore may be
      useful in treatment of children with pulmonary hypertension.

PMID- 7521467
TI  - Shock-induced refractory period extension and pharmacologic modulation of
      defibrillation threshold.
AB  - Shock-induced refractory period extension (RPE) has been suggested as a mechanism
      of electrical defibrillation. We measured RPE caused by localized field
      stimulation measured before and during infusion of disopyramide (n = 5),
      flecainide (n = 5), or E-4031 (n = 5) in anesthetized dogs and determined the
      effect of the drugs on the internal defibrillation threshold (DFT). In the
      baseline state (n = 15), 16 V/cm S2 field stimulation prolonged the effective RP
      by 36 +/- 15 ms (22 +/- 12% of RP without S2), whereas 4 and 8 V/cm S2 stimuli
      did not cause marked RPE. The RPE normalized by the RP without S2 was not
      significantly influenced by any drug (16 V/cm: disopyramide 30 +/- 11 vs. 27 +/-
      11, flecainide 25 +/- 5 vs. 19 +/- 12, and E-4031 18 +/- 13 vs. 22 +/- 14%).
      Disopyramide did not alter the defibrillation threshold (4.2 +/- 0.6-4.4 +/- 0.6
      J). In 2 dogs given flecainide, ventricular fibrillation became refractory to
      defibrillation. In contrast, E-4031 lowered the threshold from 4.5 +/- 2.4 to 2.2
      +/- 1.2 J (p < 0.01). The results suggest that flecainide and E-4031 do not
      modulate defibrillation efficiency through their effects on RPE.

PMID- 7521468
TI  - Inhibition of long-chain acylcarnitine accumulation during coronary artery
      occlusion does not alter infarct size in dogs.
AB  - We tested whether inhibition of carnitine acyl-transferase-1 (CAT-1) during
      coronary artery occlusion can limit infarct size (IS) by suppressing accumulation
      of long-chain acylcarnitines (LCAs), potentially cytotoxic intermediates of fatty
      acid metabolism. The CAT-1 inhibitor 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2
      carboxylate (POCA) was administered to dogs before 90-min occlusion and 4-h
      reperfusion of the left anterior descending or left circumflex coronary artery
      (LAD, LCX). Dogs in the LAD occlusion series received 7.5 (n = 5) or 15 (n = 2)
      mg/kg POCA intravenously (i.v.); dogs in the LCX occlusion series received 15
      mg/kg i.v. (n = 7); an equal number were treated with drug vehicle. Biopsies were
      obtained for determination of myocardial LCAs. The region at risk and IS were
      delineated by dye injection and tetrazolium staining. In vehicle-treated dogs,
      myocardial LCAs (in picomoles per milligram of wet weight +/- SEM) increased from
      11 +/- 3 to a peak of 75 +/- 24 during LAD occlusion and from 32 +/- 10 to 192 +/
      55 during LCX occlusion. In POCA-treated dogs LCAs increased from 12 +/- 2 to
      only 33 +/- 13 pmol/mg wet weight during LAD occlusion (p < 0.05 vs. vehicle) and
      did not increase significantly during LCX occlusion; 22 +/- 8 to 27 +/- 5 pmol/mg
      wet weight (p < 0.005 vs. vehicle). LCX occlusion resulted in larger areas at
      risk and larger infarcts (as a percentage of left ventricle) than did LAD
      occlusion. IS as a percentage of the region at risk did not differ significantly
      among the experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521469
TI  - Quinidine but not disopyramide prolongs cardiac Purkinje fiber action potentials
      after a pause.
AB  - Prolongation of the cardiac action potential (AP), leading eventually to early
      afterdepolarizations (EADs), is believed to underlie drug-induced long QT
      syndromes and torsade de pointes. Episodes of torsade de pointes frequently occur
      after a prolonged pause. We studied the effects of quinidine and disopyramide on
      AP duration (APD) in canine cardiac Purkinje fibers after pauses of 2,000-10,000
      ms. Standard intracellular microelectrode techniques were used to record APs from
      canine Purkinje fibers at an interstimulus interval (ISI) of 1,000 ms. Pauses of
      2,000-10,000 ms were introduced into the basic drive cycle in the presence and
      absence of subtherapeutic and therapeutic concentrations of quinidine and
      disopyramide. We observed a biphasic response in APD to quinidine and
      disopyramide at ISI = 1,000 ms. Quinidine but not disopyramide produced a marked
      dose- and time-dependent additional prolongation of APD immediately after the
      pauses. This effect was highly statistically significant. We conclude that
      disopyramide and quinidine have qualitatively different effects on APD after a
      pause and that this observation may cast some light on the apparently greater
      frequency of torsade de pointes occurring with quinidine than with disopyramide.
      Possible mechanisms include differential drug effects on outward potassium or
      inward sodium channels.

PMID- 7521470
TI  - Endothelin ETA- and ETB-receptor-mediated vasoconstriction in rat pulmonary
      arteries and arterioles.
AB  - We investigated the endothelin (ET) receptors involved in the vasoconstrictor
      responses to ET-1 in rat pulmonary arteries and arterioles and the effect of
      endothelium removal, nitric oxide (NO) synthase inhibition, and hypoxia on ET-1
      induced responses in the arteries. In isolated rat pulmonary artery rings (2-3 mm
      ID) prepared from the pulmonary artery branch before its entry into the lung, ET
      1-induced vasoconstrictor responses. These responses were mediated by the ETA
      receptor as they were competitively antagonized by the ETA receptor antagonist FR
      139317, and the ETB-receptor agonist sarafotoxin S6c (SXS6c) was a very weak
      vasoconstrictor in these vessels, inducing maximum contractions only 9% of those
      of ET-1. In contrast, in rat intrapulmonary resistance arteries (100-150 microns
      ID), SXS6c induced FR 139317-resistant contractions, and these vessels were more
      sensitive to SXS6c than to ET-1. SXS6c produced maximum contractions 92% those of
      ET-1, suggesting that ET-1-induced contractions were mediated by the ETB receptor
      in these resistance vessels. In the larger pulmonary arteries, the NO synthase
      inhibitor L-N omega nitroarginine methyl ester (L-NAME) (100 microM) potentiated
      responses to ET-1, an effect that was reversed by FR 139317. Endothelium removal
      also potentiated response to ET-1, and L-NAME had no effect on ET-1 responses in
      endothelium-denuded vessels, suggesting that in these vessels the ETA receptor
      mediated responses to ET-1 are normally suppressed by endothelium-derived
      NO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521471
TI  - Effect of metoprolol on atrial fibrillatory rate, atrioventricular nodal
      concealed conduction, and ventricular response during atrial fibrillation in
      pigs.
AB  - We wished to elucidate the effect of beta-blockade on fibrillatory rate and
      atrioventricular (AV) nodal concealed conduction during atrial fibrillation (AF).
      Subsequent to determination of the effect on atrial functional refractoriness
      with the extrastimulus technique (basic cycle length 400 ms), the effect of
      metoprolol (0.3 mg/kg) on atrial fibrillatory rate was determined in 8 open-chest
      pigs with metacholine-facilitated AF. Once stable AF was established,
      fibrillatory rate was recorded with a bipolar epicardial electrode, together with
      the ventricular response during 500 ventricular intervals. For each episode of
      AF, three indexes were calculated to determine the degree of concealed
      conduction: the ratio of the longest to the shortest ventricular interval, the
      ratio of the median ventricular interval to the median atrial interval, and the
      coefficient of variation of the ventricular intervals. Metoprolol decreased
      fibrillatory rate (571-432 beats/min, p < 0.01), suggesting a proportionate
      increase (+32%) in atrial functional refractoriness during AF that far exceeded
      the increase (+7%) during sinus rhythm (217-233 ms, p < 0.05). None of the
      indexes of concealed conduction was affected by metoprolol. Metoprolol decreases
      fibrillatory rate in AF, possibly due in part to its class I effect, causing rate
      dependent prolongation of atrial refractoriness. Despite reducing fibrillatory
      rate, metoprolol does not affect AV nodal concealed conduction measurably. Our
      results support the assumption that the reducing effect of beta-blockers on
      ventricular rate during AF is due to direct prolongation of AV nodal
      refractoriness.

PMID- 7521472
TI  - Hypoxia modifies the vasodilatory effects of nitroglycerin, prostaglandin E1, and
      hydralazine on isolated porcine coronary arteries.
AB  - To evaluate the potency of vasodilatory drugs in hypoxia, we studied the effects
      of nitroglycerin (NTG), prostaglandin E1 (PGE1), and hydralazine on porcine
      coronary artery constricted with endothelin-1 (ET-1) in both oxygenated and
      hypoxic conditions. Removal of endothelium potentiated NTG-induced relaxation in
      oxygenated conditions. Hypoxia potentiated relaxation of endothelium-intact
      arteries induced by NTG, but not relaxation of endothelium-denuded arteries.
      These findings suggest that hypoxia may modify endothelial function in NTG
      induced relaxation. The relaxation of endothelium-intact and -denuded arteries
      induced by PGE1 in hypoxia was significantly greater than that in the oxygenated
      condition. PGE1 significantly increased the content of cyclic AMP in the hypoxic
      condition; it was much greater than that in the oxygenated condition, suggesting
      that hypoxia may enhance PGE1-induced relaxation by increasing cyclic AMP levels.
      Hypoxia attenuated hydralazine-induced relaxation in both endothelium-intact and
      denuded arteries. Indomethacin and aspirin attenuated hydralazine-induced
      relaxation in the oxygenated condition, suggesting that cyclooxygenase-related
      eicosanoid(s) may be involved in hydralazine-induced relaxation. However,
      indomethacin did not alter relaxation of hypoxic arteries induced by hydralazine.
      These findings suggest that hypoxia may inactivate cyclooxygenase in hydralazine
      induced relaxation. Hypoxia may greatly modify the action of vasodilators on
      porcine coronary smooth muscle.

PMID- 7521473
TI  - Endothelin-1 causes a biphasic response in systemic vasculature and increases
      myocardial contractility in conscious rabbits.
AB  - We studied the effects of an intravenous (i.v.) bolus of endothelin-1 (ET-1, 0.2
      nmol/kg) in conscious rabbits, measuring arterial blood pressure (BP), heart rate
      (HR), myocardial contractility, and cardiac output and evaluating direct and
      indirect effects of ET-1 with pacing and pharmacologic antagonists. ET-1 caused a
      brief initial decrease in BP of 18 +/- 1 mm Hg, followed by a sustained increase
      of 26 +/- 3 mm Hg (n = 16, p < 0.001). HR increased initially by 60 +/- 11
      beats/min and then decreased by 68 +/- 6 beats/min (n = 16, p < 0.001). Left
      ventricular (LV) dP/dt increased by 2,120 +/- 380 mm Hg/s (n = 5, p < 0.01). LV
      end-diastolic pressure (LVEDP) increased by 4 +/- 1 mm Hg (n = 5, p < 0.05).
      Cardiac output (CO) increased initially by 34 +/- 4% and then decreased by 28 +/-
      3% (n = 16, p < 0.001). Total peripheral resistance (TPR) decreased initially by
      34 +/- 3% and then increased by 72 +/- 13% (n = 16, p < 0.001). Pacing did not
      alter the effect of ET-1 on arterial BP, LVdP/dt, or LVEDP. The combination of
      propranolol and scopolamine significantly reduced the increase and decrease in HR
      and the increase in LVdP/dt. None of the antagonists significantly altered the
      effect of ET-1 on TPR. ET-1 causes brief initial vasodilation and increased
      myocardial contractility, followed by sustained vasoconstriction. The vascular
      effects appear to be of greater significance than the cardiac effects at the dose
      used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521474
TI  - Effect of various angiotensin receptor antagonists on cardiovascular responses to
      angiotensin II in pithed rats.
AB  - The effects of four nonpeptide angiotensin receptor antagonists, i.e., losartan
      (AT1) PD123177 (AT2), and 4'-[(2-n-butyl-6-cyclohexylaminocarbonylamino
      benzimidazole-1-yl)- methyl]biphenyl-carboxylic acid (BIBS 39; AT1 and AT2), and
      2-n-butyl-1-[4-(6-carboxy-2,5-di-chlorbenzoylamino)-benzyl]-6-N-
      (methylaminocarbonyl)-n-pentylamino-benzimidazole (BIBS 222; AT1 and AT2) on
      cardiovascular responses to angiotensin II (AII) were investigated in propranolol
      pretreated pithed rats. AII (0.01-10 nmol/kg intravenously, i.v.) induced a dose
      dependent increase in diastolic blood pressure (DBP), the rate of increase in
      left ventricular pressure (LVdP/dtmax), cardiac output (CO), and total peripheral
      resistance (TPR) without changing LV end-diastolic pressure (LVEDP) or heart rate
      (HR). Losartan 3 and 10 mg/kg i.v. caused dose-dependent parallel rightward
      shifts of the dose-response curves (DBP and LVdP/dtmax) without altering the
      maximal responses to AII. PD123177 (100 mg/kg i.v.) did not influence the dose
      response curves for AII significantly. BIBS 39 (1, 3, and 10 mg/kg i.v.) and BIBS
      222 (1, 3, and 10 mg/kg, i.v.) shifted the dose-response curves (DBP and
      LVdP/dtmax) for AII to the right. Although these two compounds (BIBS 39 1, 3, and
      10 mg/kg and BIBS 222 1 and 3 mg/kg) did not alter the maximal increase in DBP to
      angiotensin AII, they decreased the maximal increase in LVdP/dtmax by
      approximately 35%. BIBS 39 (3 and 10 mg/kg) significantly reduced the increase in
      CO caused by AII and therefore mean arterial pressure (MAP), whereas the AII
      induced increase in TPR remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521475
TI  - New dihydropyridine lacidipine persistently inhibits L-type calcium currents in
      GH3 cells.
AB  - We studied the effects of two antagonist dihydropyridines (DHPs) on calcium
      currents in cultured pituitary GH3 cells by the perforated patch-clamp method. At
      depolarizing voltages, GH3 cells present both the low-voltage-activated (LVA),
      fast-inactivating T-type calcium channel and the high-voltage-activated (HVA),
      fast-deactivating L-type calcium channel. As already demonstrated in whole-cell
      experiments and in perforated-patch configuration, 1 microM nimodipine reversibly
      inhibited < or = 80% of L-type calcium channels when applied in the external bath
      solution. At concentrations of 0.1-1 microM, the new DHP lacidipine inhibited L
      type calcium current, but this inhibition was very persistent and never reversed,
      even after prolonged washout, in a typical perforated patch-clamp experiment (<
      or = 2h). Like that of other DHPs, the potency of lacidipine block increases at
      more depolarizing holding potentials (HPs). The time needed to inhibit 50% (t1/2)
      of L-type calcium current was decreased by increasing lacidipine concentration;
      t1/2 was 22 +/- 3 s with addition of 1 microM lacidipine; this concentration
      inhibited < or = 86 +/- 1% of the L-type current. The persistent blocking induced
      by lacidipine can be explained in terms of a strong interaction of the drug with
      the membrane phospholipids, as a consequence of the enhanced hydrophobicity and
      specific location of this molecule with respect to other DHPs.

PMID- 7521476
TI  - Chronic versus acute effects of amiodarone on the Vmax-conduction velocity
      relationship and on the space constant in canine myocardium.
AB  - Isolated tissue experiments (canine ventricular epicardium) and computer
      simulations were used to characterize the relationship between changes in maximum
      rate of depolarization during upstroke (Vmax) and the conduction velocity (theta)
      induced after long-term therapy with amiodarone and to compare these data with
      those obtained after acute superfusion with either desethylamiodarone or the
      parent compound. After chronic amiodarone, the changes in Vmax were linearly
      related to the square of the changes in theta during longitudinal propagation
      (LP) (slope = 0.93, r = 0.93, p = NS with respect to slope = 1), whereas during
      transverse propagation (TP), the slope of the relationship between both variables
      was slightly decreased (slope = 0.88, r = 0.96, p < 0.05 with respect to slope =
      1). Similar results were observed after acute superfusion with desethylamiodarone
      (LP), (slope = 1, r = 0.05, p = NS with respect to slope = 1). In contrast, a
      significant increase in slope (p < 0.05 with respect to slope = 1) was observed
      after acute superfusion (slope = 1.45, r = 0.85 and slope = 1.48, r = 0.75 during
      LP and TP, respectively). In addition, the space constant (lambda) after chronic
      amiodarone (1.05 +/- 0.06 mm) was not significantly different from control (0.98
      +/- 0.04 mm), but was slightly though significantly increased after acute
      amiodarone administration (1.07 +/- 0.03 mm, p < 0.03). Data are mean +/- SEM.
      Experimental data from chronic amiodarone were well fitted in a one-dimensional
      Beeler-Reuter-based discrete cable by reducing sodium conductance (GNa)
      exclusively. In contrast, data from acute superfusion were fitted only when
      junctional resistance (rj) and GNa were simultaneously reduced. These data
      suggest that acute amiodarone may modify both active and passive membrane
      properties whereas chronic amiodarone appears to alter only the active
      properties; the data further indicate that desethylamiodarone may play an
      important role in the mechanism of action of chronic amiodarone treatment.

PMID- 7521478
TI  - Effects of the new phosphodiesterase-III inhibitor R80122 on contractility and
      calcium current in human cardiac tissue.
AB  - The selective phosphodiesterase III (PDE-III) inhibitor R80122 ((E)-N-cyclohexal
      N-methyl-2-[[[phenyl-(1,2,3,5- tetrahydro-2-oxoimidazo-[2,1b]-quinazolin-7-yl)
      methylene]-a mino]-oxy]-acetamide) has been reported to possess greater
      cardiotonic potency and less side effects than the standard compounds milrinone
      or enoximone. To characterize this new compound further, we investigated the
      effects of R80122 on force of contraction (Fc) and calcium current (ICa) in human
      right atrium (HRA) and human left ventricle (HLV) with reference to the
      nonselective PDE-inhibitor IBMX (3-isobutyl-1-methylxanthine). With "late"
      exposure (300- to 330-min equilibration) of human atrial trabeculae, R80122 (3
      microM) increased Fc by 60 +/- 11%; log EC50 was -6.2 +/- 0.1. R80122 (3 microM)
      induced a relative leftward shift of forskolin concentration-response curves by
      0.34 log units; the respective value for IBMX (20 microM) was 0.46. A positive
      inotropic effect of R80122 was also shown in guinea pig papillary muscles. ICa
      was measured in voltage-clamped isolated myocytes of human right atrial and left
      ventricular (LV) tissue, and, for comparison, guinea pig ventricle. With clamp
      steps from -40 to +5 mV, R80122 (3 microM) increased peak ICa from 3.1 +/- 0.2 to
      5.4 +/- 0.3 pA/pF in HRA cells, from 2.9 +/- 0.4 to 5.1 +/- 0.6 pA/pF in HLV
      cells, and from 4.4 +/- 0.3 to 6.6 +/- 0.5 pA/pF in guinea pig myocytes. IBMX 20
      microM increased ICa to a greater extent. Washout or addition of carbachol 10
      microM partially reversed the effect of R80122. Voltage dependence, inactivation
      time course, and steady-state inactivation of ICa were little changed by either
      compound. Stimulation of Ca2+ influx by L-type Ca2+ channels contributes to the
      positive inotropic effect of the selective PDE-III inhibitor R80122.

PMID- 7521479
TI  - Prolonged regional vasoconstriction produced by NG-nitro-L-arginine in conscious
      sheep.
AB  - Nitric oxide (NO) is a potent endothelium-derived vasodilator whose synthesis can
      be blocked both in vitro and in vivo by structural analogues of its precursor, L
      arginine (L-ARG). We examined the dose-response profile of one such analogue, NG
      nitro-L-arginine (NOLA) in conscious sheep (n = 4) and used continuous monitoring
      techniques to study long-term changes in mean arterial pressure (MAP), heart rate
      (HR), and cardiac output (CO) and the relative responsiveness of the coronary,
      mesenteric, renal, and hindlimb vascular beds to NOLA [10 mg/kg, intravenous
      (i.v.) bolus] in 5 sheep. NOLA (3 and 10 mg/kg) increased MAP at 1 h from 73 +/-
      4 to 86 +/- 3 mm Hg (p < 0.05) and 73 +/- 1 to 106 +/- 8 mm Hg (p < 0.05),
      respectively. CO and HR decreased significantly after 10 mg/kg NOLA. Plasma
      endothelin (ET) level was unchanged after all doses of NOLA. Continuous
      monitoring of MAP, CO, and blood flow for 24 h before and after NOLA injection
      showed that MAP increased rapidly owing to a decrease in total peripheral
      conductance (TPC), with short-term reflex decreases in HR and prolonged decreases
      in CO and stroke volume (SV). Coronary and iliac conductances changed
      comparatively little. Renal conductance decreased by 43% at 80 min, but was not
      different from control after 6 h. The greatest and most sustained decrease in
      conductance, by a maximum of 55% of control levels at 110 min, occurred in the
      mesenteric bed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521480
TI  - Effects of early and late therapy with perindopril on survival and myocardial
      inotropic state in experimental dilated cardiomyopathy.
AB  - We wished to test (a) whether single-drug therapy with a low dose of the
      angiotensin-converting enzyme (ACE) inhibitor perindopril has the capacity to
      improve early survival of the cardiomyopathic Syrian hamster (CSH); (b) whether
      early treatment with perindopril modifies CSH survival to a greater extent than
      perindopril treatment initiated later in the course of the disease; and (c) the
      effects of early and late perindopril therapy on the intrinsic contractility of
      left ventricular (LV) papillary muscle. We studied CSH from the Bio 53.58 dilated
      strain (n = 76), in which myocardial necrosis is known to develop from age 30
      days, whereas congestive heart failure (CHF) is observed only after age 6 months.
      Animals were randomly assigned to three groups. In early-treated animals,
      perindopril (1 mg/kg body weight once daily in distilled water) was administered
      by force-feeding from age 1 month to 9 months (PE1, n = 21). Animals receiving
      delayed treatment received distilled water from age 1 month to 6 months, followed
      by 1 mg/kg body weight from age 6 to 9 months (PE2, n = 34). Controls received
      distilled water from age 1 month to 9 months (C, n = 21). At endpoint (9 months),
      mechanical properties of LV papillary muscles and serum ACE activity were studied
      in a subgroup of 32 CSH (C, n = 8; PE1, n = 10; and PE2, n = 14). Maximum
      unloaded shortening velocity, maximum extent of systolic shortening in twitch
      with preload only, and normalized peak of isometric active force were
      measured.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521481
TI  - Potassium channel opening properties of thiazide diuretics in isolated guinea pig
      resistance arteries.
AB  - We examined the role of K+ channels in mediating the acute vascular actions of
      hydrochlorothiazide, indapamide, cicletanine, and cromakalim, studying the effect
      of K+ channel blockers on drug-induced relaxation and drug-induced 86Rb efflux in
      guinea pig mesenteric arteries. Cromakalim-induced relaxation was unaffected by
      charybdotoxin, apamin, or phencyclidine (PCP) but was reduced by 75% (with 30
      microM cromakalim) by glibenclamide (p < 0.001). Cromakalim increased 86Rb efflux
      from guinea pig vessels, an effect that was abolished by glibenclamide.
      Hydrochlorothiazide and cicletanine-induced relaxations have been shown to be
      inhibited by charybdotoxin by unaffected by glibenclamide, apamin, or PCP.
      Hydrochlorothiazide and cicletanine increased 86Rb efflux from guinea pig
      mesenteric arteries. These increases were abolished by charybdotoxin. Indapamide
      induced relaxation was not affected by incubation with any of the K+ channel
      blockers. Indapamide did not alter basal 86Rb efflux. The results suggest that in
      guinea pig mesenteric arteries indapamide-induced relaxation is not mediated by
      an action on K+ channels. Cromakalim-induced effects are mediated by KATP. Large
      conductance KCa mediates the hydrochlorothiazide and cicletanine-induced vascular
      effects in part.

PMID- 7521482
TI  - Possible mechanisms for the venular constriction elicited by Ruscus extract on
      hamster cheek pouch.
AB  - We investigated the influence of alpha-adrenoceptors blockers and calcium
      blockers on the effects of the venotonic agent Ruscus extract on the diameter of
      arterioles (ID 10-70 microns) and venules (ID 20-135 microns) of hamster cheek
      pouch microvasculature in vivo. For microcirculatory measurements, the
      preparations were placed under an intravital microscope coupled to a closed
      circuit TV system. The TV monitor display was used to obtain arteriolar and
      venular internal diameter recordings (always at the same site) by an image
      shearing device. All drugs were applied topically. Ruscus extract was tested in
      different concentrations and in combination with prazosin (alpha 1-adrenoceptor
      antagonist), rauwolscine (alpha 2-adrenoceptor antagonist), or diltiazem (calcium
      blocker). Topical application of Ruscus extract elicited concentration-dependent
      responses in the studied vessels: arterioles remained unchanged in the
      concentration range tested, whereas venules remained unchanged or constricted
      depending on the concentration used. The observed venular constriction could be
      blocked by low concentrations (10(-9) M) of prazosin or diltiazem and by high
      concentrations (> 10(-6) M) of rauwolscine. Our results suggest that the venular
      constriction elicited by Ruscus extract in vivo, at the microcirculatory level,
      is mediated by calcium and by alpha-adrenoceptors and further support data
      previously reported on larger vessels and on patients with venous insufficiency.

PMID- 7521477
TI  - Effects of nisoldipine on endothelin-1- and angiotensin II-induced
      immediate/early gene expression and protein synthesis in adult rat ventricular
      cardiomyocytes.
AB  - The cellular mechanisms by which dihydropyridine-type calcium antagonists lead to
      regression of hypertension-related cardiac hypertrophy have not been clarified.
      We previously showed that angiotensin II (AII) and endothelin-1 (ET-1) induce
      protein synthesis in isolated adult rat cardiomyocytes, probably through protein
      kinase C (PKC) as second messenger and the gene product of the early growth
      response gene-1 (Egr-1) as third messenger. We now show that the dihydropyridine
      derivative nisoldipine inhibits AII- and ET-1-induced protein synthesis at low
      concentrations (IC50 7.5 nM for 0.1 microM ET). Induction of c-fos and Egr-1 mRNA
      by AII and ET was completely blocked by nisoldipine. Therefore, nisoldipine may
      influence the signal transduction pathway, i.e., through PKC. These results
      provide a potential pressure-independent mechanism by which nisoldipine may
      influence development of cardiac hypertrophy.

PMID- 7521483
TI  - Attenuation of cyclosporine A-induced vascular toxicity by ramipril.
AB  - We wished to determine whether chronic inhibition of angiotensin-converting
      enzyme (ACE) prevents the vascular toxicity of cyclosporine A (Cx). In aortas
      isolated from rats treated with ramipril [10 mg/kg/day orally (p.o.) for 4
      weeks], the endothelium-dependent relaxations to acetylcholine (ACh) were
      potentiated (the area under the curve (AUC) decreased from 154 +/- 35 to 63 +/-
      12, p < 0.05), but contractions induced by phenylephrine (PE) and angiotensin II
      (AII) were not affected. Therefore, we studied three groups of rats in parallel.
      Group 1 received ramipril 10 mg/kg/day p.o. for 4 weeks and ramipril 10 mg/kg/day
      p.o. plus Cx 20 mg/kg/day intramuscularly, in fifth week; group 2 received Cx
      only (20 mg/kg/day i.m. for 1 week), and group 3 served as control. In group 2,
      ACh-induced relaxations were reduced as compared with those of the control group
      (AUC increased from 141 +/- 34 to 240 +/- 32, p < 0.05), whereas in group 1, AUC
      was not significantly different from that of group 3 (195 +/- 28 vs. 141 +/- 34).
      In group 2, PE- and AII-induced contractions were enhanced; AUC values for PE and
      AII were 495 +/- 45 versus 348 +/-38 in group 3 and 424 +/- 28 versus 314 +/- 17
      in group 3, respectively (p < 0.05). In group 1, AUCs for PE and AII were not
      significantly different from those of group 3. After mechanical removal of the
      endothelium, the increased responsiveness to PE and AII persisted in group 2
      whereas AUC values in group 1 were not different from those of group 3.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7521485
TI  - Effects of protein kinase C activator and inhibitor on adrenal catecholamine
      release in response to splanchnic nerve stimulation in anesthetized dogs.
AB  - Effects of protein kinase C (PKC) activator and inhibitors on adrenal
      catecholamine release were examined in anesthetized dogs. Output of epinephrine
      (EPI) and norepinephrine (NE) was determined from adrenal venous blood by high
      performance liquid chromatography (HPLC) with electrochemical detection. All
      drugs were infused intraarterially (i.a.) into the adrenal gland through the
      phrenic abdominal artery. Infusion of the PKC activator phorbol-12,13-dibutyrate
      (PDB 0.1 micrograms/min) increased EPI and NE output during basal state and
      enhanced increases in catecholamine output induced by splanchnic nerve
      stimulation (SNS 1 and 3 Hz). These effects of PDB were abolished by the PKC
      inhibitor staurosporine (SSP 0.3 microgram/min), when both drugs were infused
      simultaneously. Infusion of SSP (0.1, 0.3, and 1 micrograms/min) caused a dose
      dependent inhibition of the SNS-induced increases in EPI and NE output. SNS
      induced increases in catecholamine output were also inhibited by another PKC
      inhibitor polymyxin B (PMB 0.1, 0.3, and 1 micrograms/min) and by the
      phospholipase C (PLC) inhibitor neomycin (NM 0.3, 1, and 3 mg/min). SSP, PMB, and
      NM did not affect basal output of EPI and NE. These results suggest that
      activation of PKC promotes release of adrenal catecholamines and provide indirect
      evidence that activation of PKC and PLC may be involved in SNS-induced release of
      catecholamines from dog adrenal gland.

PMID- 7521484
TI  - Effect of ibopamine on ventricular remodeling after experimental myocardial
      infarction: a comparison with captopril.
AB  - Remodeling after myocardial infarction (MI) is influenced not only by hemodynamic
      but possibly by neurohumoral factors as well. Ibopamine is an orally active
      dopamine agonist (DA) with both hemodynamic and neurohumoral properties in
      humans. The latter property prevails in rats. To study the dose-dependent effect
      of ibopamine on myocardial remodeling and compare it with the effect of
      captopril, we randomized rats with (n = 27) or without (n = 27) experimental MI
      to captopril (25 mg/kg/day), low-dose ibopamine (10 mg/kg/day), high-dose
      ibopamine (30 mg/kg/day), or no treatment. After 8-week treatment, hearts were
      isolated and left ventricular (LV) function, LV cavity volume, and infarct size
      (IS) were evaluated. Both ibopamine and captopril significantly reduced plasma
      norepinephrine (NE) levels in rats with MI. In untreated but not in treated
      infarcted rats, LV function was significantly reduced as compared with that of
      controls. IS was reduced in all three active treatment groups as compared with
      untreated rats. LV cavity volume was significantly increased in untreated rats
      with MI as compared with controls. This dilatation was attenuated by both
      ibopamine and captopril. Ibopamine, comparable to captopril, administered early
      after coronary ligation reduced IS and subsequent ventricular dilatation,
      resulting in preservation of cardiac function in this rat model. This observation
      suggests a major role for neurohumoral activation in the process of remodeling.

PMID- 7521486
TI  - Effects of RS-2135, a novel class I antiarrhythmic agent, on sustained
      ventricular tachycardia after coronary embolization in conscious dogs.
AB  - To assess the ability of RS-2135, a novel class I antiarrhythmic agent to
      suppress ischemia-induced ventricular arrhythmias, we produced myocardial
      infarction (MI) by introducing a glass bead into the coronary artery of the dog
      (bead model). Ventricular arrhythmias after coronary embolization were as severe
      and long-lasting as those that occur after two-stage coronary artery ligation as
      described by Harris. RS-2135 (1.25 and 2.5 mg/kg intravenously, i.v.) suppressed
      sustained ventricular tachycardia (SVT) 24 h after coronary embolization in the
      bead model. The antiarrhythmic effects of i.v. administration of RS-2135 were
      more potent and more long-lasting than those of lidocaine (5 and 10 mg/kg i.v.),
      mexiletine (5 and 10 mg/kg i.v.), disopyramide (2.5 and 5 mg/kg i.v.), and
      flecainide (2.5 and 5 mg/kg i.v.). The antiarrhythmic effects of oral (p.o.)
      administration of RS-2135 were evaluated 48 h after coronary embolization. RS
      2135 (10 mg/kg p.o.) was equipotent to flecainide (10 mg/kg p.o.) and twice as
      potent as disopyramide (20 mg/kg p.o.) and mexiletine (20 mg/kg p.o.). Onset of
      antiarrhythmic effects after p.o. RS-2135 was slower than that of other drugs.
      These data suggest that the bead model is as useful as the Harris model for
      evaluation of the antiarrhythmic potential of chemicals and that RS-2135, either
      i.v. or p.o., is effective against SVT after acute MI.

PMID- 7521488
TI  - Effects of trimetazidine on ischemic contracture in isolated perfused rat hearts.
AB  - Trimetazidine (1-[2,3,4-trimethoxibenzyl)]-piperazine, TMZ) is a drug with a
      proposed metabolically based antiischemic action. Because ischemic contracture is
      a serious complication of ischemia and is considered metabolic in origin, we
      studied the effect of trimetazidine (TMZ) on development of ischemic contracture
      in experimental low-flow ischemia. TMZ was either added to the perfusion fluid or
      given as pretreatment to the donor rats. Langendorff-perfused isolated rat hearts
      were submitted to 30-min subtotal global ischemia (residual flow = 0.2 ml/min, n
      = 6 per group) (normal flow = 12.4 +/- 0.8 ml/min, heart fresh weight = 0.9 +/-
      0.3 g). Ischemic contracture was measured by a water-filled intraventricular
      balloon. Thereafter, the hearts were reperfused for 20 min and recovery of
      intraventricular pressure was monitored. Furthermore, because the mechanisms of
      action of TMZ may involve cellular energy metabolism, we assessed throughout
      glycolytic flux by collecting the coronary effluent every 5 min during control
      perfusion, ischemia, and reperfusion periods. Animals from the pretreated groups
      received TMZ [3 mg/kg orally (p.o.) twice daily] for 5 days. Animals from the
      control group received placebo for the same time period. Concentrations of 10(-6)
      and 10(-4) M were used when the drug was added to the perfusate. In our
      experimental conditions, TMZ pretreatment alone had no measurable
      cardioprotective effect, but addition to the perfusate of TMZ 10(-6) M,
      approximately a therapeutic concentration in humans, reduced ischemic contracture
      in both pretreated and control groups and improved postischemic recovery of
      developed pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521487
TI  - Regional oxygen consumption persists in dyskinetic canine myocardium.
AB  - Regional myocardial O2 consumption was measured in anesthetized dogs both in
      baseline conditions and during intracoronary infusion of lidocaine, verapamil,
      sodium citrate, or 2,3-butanedione-monoxime (BDM). Despite regional hypokinesis
      and dyskinesis during drug infusion, regional O2 consumption was reduced only 30
      40% by lidocaine, verapamil, and citrate and not at all by BDM. These results
      cast doubt on an important assumption of the "hibernation" theory: the protective
      matching of regional perfusion and contraction.

PMID- 7521489
TI  - Is guanidino succinate a precursor for nitric oxide synthesis in rat vascular
      tissue?
AB  - Although L-Arginine (L-Arg) is considered the physiological precursor of nitric
      oxide (NO) synthesis in endothelial cells, recent experiments suggested that
      another guanidino derivative, guanidino succinate, may also serve as a major
      source of NO in this tissue. We tested this hypothesis in rat aortas, using two
      experimental situations in which L-Arg had previously shown significant activity,
      i.e., the ability to counteract contractile responses to the L-Arg analogue NG
      nitro-L-arginine methyl ester (L-NAME) and the relaxation observed after
      prolonged incubation in physiologic buffer. Rat aortic rings, with or without
      endothelium, were suspended in organ chambers for recording of isometric tension
      and were contracted by phenylephrine (PE). After a brief incubation period (0.5
      h), L-Arg, D-Arg, or guanidino succinate induced only minor relaxations in rings
      with or without endothelium. In the presence of L-NAME, L-Arg (but not the D
      enantiomer), induced concentration-dependent relaxations of rings with
      endothelium (relaxation to L-Arg 10(-3) M 52 +/- 13%), reflecting a reversal by L
      Arg of the L-NAME-induced potentiation of the contraction to PE. In contrast to L
      Arg, guanidino succinate was less effective in the presence than in the absence
      of L-NAME (relaxation to guanidino succinate 10(-3) M before L-NAME 37 +/- 8% and
      after L-NAME 14 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521490
TI  - Antiischemic effects of intravenous diazepam in patients with coronary artery
      disease.
AB  - Diazepam (DZP) is commonly used in treatment of patients with acute ischemic
      syndromes to allay anxiety, but benzodiazepines reduce myocardial contractility
      and increase myocardial blood flow. To investigate the antiischemic effect of
      DZP, we studied 13 patients with a positive exercise test and angiographically
      documented coronary artery disease. All patients were submitted to a randomized,
      placebo-controlled trial using 0.9% NaCl infusion as placebo and intravenous
      (i.v.) diazepam (0.1 mg/kg in 20 min). Exercise tests performed immediately after
      the infusions showed that as compared with placebo, DZP significantly prolonged
      time to 1-mm ST-segment depression (557 +/- 198 vs. 428 +/- 226 s, p < 0.0001)
      and total exercise duration (624 +/- 177 vs. 561 +/- 188 s, p < 0.007). Rate
      pressure product (RPP) at 1-mm ST-segment depression was not significantly
      different with the two treatments. DZP significantly delays onset of exercise
      induced myocardial ischemia in patients with coronary artery disease. Because RPP
      at onset of ischemia was similar to that recorded with placebo despite greater
      levels of external workload, the antiischemic action of DZP appears to be
      mediated, at least partially, by a reduction in myocardial oxygen consumption.

PMID- 7521492
TI  - Effects of S-dobutamine on ischemic myocardium caused by coronary artery
      narrowing.
AB  - Cardiovascular effects of S-dobutamine were compared with effects of vehicle and
      other catecholamines in dogs during and after 3 days of approximately 90%
      ligation of the left anterior descending coronary artery (LAD). Twenty-four hours
      after LAD ligation, dogs infused with S-dobutamine (2.5 micrograms/kg/min
      intravenously, i.v.) maintained systolic blood pressure (SBP 149 +/- 6 mm Hg),
      diastolic blood pressure (DBP 100 +/- 6 mm Hg), and aortic dP/dt60 (2.8 +/- 0.2 s
      1), with no significant changes from preligation values. In comparison, saline
      treated dogs showed decreases in arterial BP and contractility: SBP 121 +/- 4 mm
      Hg; DBP 85 +/- 3 mm Hg; and aortic dP/dt60 was 1.9 +/- 0.1 s-1. S-Dobutamine
      infused dogs had a heart rate (HR) of 148 +/- 5 beats/min with 44 +/- 14
      beats/min premature ventricular contractions (PVCs), whereas dogs infused with
      saline, R-dobutamine, dopamine, norepinephrine (NE), or isoproterenol (ISO) all
      displayed a significantly greater number of PVCs at 24 h. Myocardial necrosis was
      limited by S-dobutamine treatment (2.5 micrograms/kg/min i.v. for 54 h). As
      demonstrated by histologic examination, S-dobutamine ameliorated the effects of
      ischemia as compared with vehicle, R-dobutamine, dopamine, hexamethonium, NE, or
      ISO. Myocardial tissue electrolytes, quantified 72 h after LAD ligation, were
      maintained by S-dobutamine-infused dogs in all sections of left ventricle (LV);
      but in saline-treated dogs, Ca2+ increased eightfold, Na+ increased twofold, and
      both K+ and Mg2+ decreased 50% in tissue "at risk" as compared with tissues "not
      at risk." Coronary nutrient blood flow (CNBF) to myocardial capillary vessels was
      calculated by radiolabeled microspheres 2 h after LAD ligation. As compared with
      CNBF in untreated hearts, endocardial CNBF in hearts receiving S-dobutamine (5
      micrograms/kg/min i.v.) increased from 26 +/- 8 to 49 +/- 15 ml/min/100 g in
      tissue at risk, from 102 +/- 26 to 217 +/- 50 in "border zone," and from 133 +/-
      13 to 215 +/- 41 in tissue not at risk. CNBF values in animals receiving vehicle
      infusion were not significantly different from CNBF values measured after
      ligation only. The S-enantiomer of dobutamine, infused in dogs for 54 h after
      coronary artery ligation, maintained cardiac performance, electrolyte balance,
      and myocardial cellular viability and reduced incidences of arrhythmias through
      its ability to increase CNBF without increasing HR.

PMID- 7521491
TI  - NG-nitro-L-arginine contracts vascular smooth muscle by an endothelium
      independent mechanism.
AB  - We characterized the contractile effect of the nitric oxide (NO) synthase
      inhibitor NG-nitro-L-arginine (L-NNA) in endothelium-denuded rat aortic rings.
      Incubation with L-NNA (4 x 10(-6)-6.4 x 10(-5) M) for 5 h dose-dependently
      contracted endothelium-denuded aortic rings. In contrast, incubation with NG
      nitro-D-arginine (D-NNA 6 x 10(-6)-4 x 10(-4) M), diphenyleneiodonium (DPI, NO
      synthase inhibitor, 3.2 x 10(-6) M) or dexamethasone (10(-7) M, inhibitor of
      expression of inducible NO synthase) did not contract the denuded rings. The L
      NNA-induced contraction was not significantly altered by the presence of the
      endothelium or by pretreatment with L-arginine (L-Arg 2 x 10(-3) M) or
      lipopolysaccharide (100 ng/ml). These results suggest that L-NNA causes slow
      contraction of endothelium-denuded vascular smooth muscle (VSM) by a mechanism
      independent of the inhibition of constitutive or inducible NO biosynthesis.

PMID- 7521493
TI  - Diminished insulin receptors on erythrocyte ghosts in nonobese patients with
      essential hypertension independent of hyperinsulinemia.
AB  - Hypertension is associated with insulin resistance and dyslipidemia in a syndrome
      named X. Epidemiologic evidence also supports a link between hyperinsulinemia and
      blood pressure (BP), independent of obesity and non-insulin-dependent diabetes
      mellitus. To assess the possible role of insulin receptors in this syndrome, we
      studied insulin binding by erythrocyte ghosts in patients with moderate essential
      hypertension with or without fasting or postglucose hyperinsulinemia. We measured
      plasma glucose and insulin before and at 30, 60, and 120 min after administration
      of 75 g glucose in 62 hypertensive patients and 20 matched normotensive controls.
      Both groups had comparable age (mean 45 years) and waist/hip ratios (mean 0.88).
      Patients undergoing antihypertensive treatment did not receive antihypertensive
      medication for 3 weeks. Patients with fasting or postglucose hyperglycemia were
      excluded from the study. Insulin binding to erythrocyte ghosts was significantly
      decreased (p < 0.001) to almost half the values of controls (6.5% specific
      binding) in both patients with hyperinsulinemic (3.2% specific binding) and those
      with normoinsulinemic (3.9% specific binding) hypertension. Scatchard analysis
      demonstrated that this was due to a lesser number of insulin receptors. These
      data indicate that patients with essential hypertension can show decreased
      erythrocyte insulin receptors without detectable hyperinsulinemia.

PMID- 7521494
TI  - Intravenous metoprolol preceding thrombolysis in acute thrombotic myocardial
      infarction in the dog; effects on infarct size, myocardial blood flow, and left
      ventricular function.
AB  - Intravenous (i.v.) metoprolol preceding thrombolysis in an anesthetized dog model
      of thrombotic occlusion of the anterior descending coronary artery helps limit
      infarct size (IS). We wished to determine whether these effects are caused at
      least in part by enhancement of collateral blood flow to the area at risk (AAR).
      Thrombotic occlusion was provoked by a copper-coil technique. We measured
      intracardiac pressures and their derivatives by catheter-tip micromanometers,
      cardiac output (CO) by thermodilution method, regional myocardial blood flow
      (RMBF) by radioactive microspheres technique, global and regional left
      ventricular (LV) function by ventriculography, and IS with triphenyltetrazolium
      at the end of the experiment. Measurements were performed before and after 60-min
      occlusion and after 30- and 90-min reperfusion. Received fifteen minutes after
      occlusion, 12 dogs metoprolol 0.3 mg/kg i.v. followed by 0.3 mg/kg/h; 12 received
      saline. Thrombolysis was performed in all dogs after 60-min occlusion with
      recombinant tissue-type plasminogen activator (rt-PA) 10 micrograms/kg/min for 30
      min. Hemodynamic findings were similar in both groups. During occlusion,
      collateral flow to total AAR (18.6 +/- 7.5 vs. 11.0 +/- 6.1 ml/min/100 g), to its
      subepicardial (22.1 +/- 8.1 vs. 12.2 +/- 7.2 ml/min/100 g), midmyocardial (16.0
      +/- 8.9 vs. 8.0 +/- 5.5 ml/min/100 g), and endocardial (14.1 +/- 8.1 vs. 7.3 +/-
      6.0 ml/min/100 g) layers was higher (p < or = 0.03) in metoprolol than in placebo
      treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521496
TI  - Influence of inhibition of endothelium-derived nitric oxide formation to effects
      of vasoconstrictor agents neuropeptide Y, clonidine, and ergonovine on coronary
      vascular resistance.
AB  - To determine whether inhibition of endothelium-derived nitric oxide (EDNO)
      synthesis enhances the effects of exogenous vasoconstrictor agents on the
      coronary vasculature, we examined the effects of neuropeptide Y (NPY), clonidine,
      and ergonovine on coronary vascular resistance (CVR) with and without EDNO
      inhibitor and compared the results. In 15 anesthetized mongrel dogs, the left
      circumflex coronary artery (LCX) was perfused with arterial blood from the left
      common carotid artery through an extracorporeal bypass tube and LCX blood flow
      was measured with an electromagnetic flowmeter. Nine of the dogs were pretreated
      with intracoronary NG-nitro-L-arginine methyl ester (L-NAME 300 microM in LCX
      blood) (L-NAME group) and the other 6 were treated with normal saline (vehicle
      group). Three doses of NPY (4.3, 43, 430 ng/kg), two doses of clonidine (30 and
      300 ng/kg), and one dose of ergonovine (20 micrograms/kg) were infused into LCX.
      NPY decreased LCX flow and increased CVR dose dependently in both groups, and
      there was no significant difference in the dose-response relation between the two
      groups. Clonidine decreased LCX flow and increased CVR in both groups, and there
      was no difference in the effect between the groups. In contrast, ergonovine
      decreased LCX flow and increased CVR to a greater degree in the L-NAME group than
      in the vehicle group (p < 0.01). Thus, inhibition of EDNO synthesis by L-NAME did
      not result in enhancement of the vasoconstrictor effects of NPY and clonidine,
      whereas it significantly enhanced the effect of ergonovine, possibly through
      inhibition of ergonovine-induced EDNO release.

PMID- 7521495
TI  - Effects of a new calcium antagonist, CD-832, on coronary and systemic
      hemodynamics in conscious dogs.
AB  - The effects of a new calcium antagonist, CD-832, on coronary and systemic
      hemodynamics were compared with those of nifedipine in conscious dogs. A pair of
      10-MHz piezoelectric crystals and an electromagnetic flow probe were placed on
      the left circumflex coronary artery (LCX) under sterile conditions to measure
      epicardial coronary artery diameter (CoD) and coronary blood flow (CBF),
      respectively. CD-832 (30, 100, and 300 micrograms/kg) and nifedipine (3, 10, and
      30 micrograms/kg) produced dose-related increases in large epicardial CoD and in
      CBF. At doses of CD-832 (100 micrograms/kg) and nifedipine (30 micrograms/kg),
      producing the same increases in CoD and CBF, the duration of increases in CoD and
      in CBF was markedly longer after CD-832 than after nifedipine. CD-832 and
      nifedipine produced dose-related decreases in aortic blood pressure (AoP) and
      reflex increases in heart rate (HR). However, nifedipine produced significantly
      (p < 0.01) greater tachycardia than CD-832 in equieffective hypotensive doses.
      These results demonstrate that CD-832 produces sustained dilation of both large
      epicardial coronary arteries and small resistance vessels and that the degree of
      tachycardia after CD-832 is significantly less than that after nifedipine.

PMID- 7521497
TI  - Regulation of adenosine receptor function by theophylline in rat aorta.
AB  - The effect of chronic theophylline treatment on adenosine receptor function was
      investigated in rat aorta. Male Wistar rats were fed theophylline (1 g/L) in
      drinking water for 30 days. The relaxation-response curves to various adenosine
      receptor agonists, nonselective 5'-N-ethylcarboxamidoadenosine (NECA), A2
      selective 2-phenylaminoadenosine (CV-1808), and A1-selective N6-(2-endo
      norbornyl) adenosine (S-ENBA) were generated in aortic rings from control and
      treated rats. The relaxation curves to both NECA and CV-1808 (10(-9)-10(-4) M)
      were significantly attenuated in treated rings (endothelium intact) as compared
      with control. S-ENBA showed a contraction at a lower concentration (10(-10)-10(
      6) M) in treated rings as compared with control. Because S-ENBA is highly A1
      selective, it produced relaxation only at 10(-4) M. Similar to that of adenosine
      analogues, the isoproterenol (ISO 10(-9)-10(-5) M) concentration-relaxation curve
      was shifted to the right in treated rats. Endothelium removal of the vascular
      rings decreased the magnitude of relaxation to these agonists and eliminated the
      difference in relaxation between control and treated groups. The relaxation to
      acetylcholine (ACh), an endothelium-dependent relaxing agent, was also attenuated
      in the theophylline-treated group. The relaxation responses to forskolin (10(-11)
      10(-8) M) and sodium nitroprusside (SNP 10(-10)-10(-7) M) were unaltered in
      treated rats. These data suggest an endothelium-dependent downregulation of
      adenosine receptor function together with beta-adrenoceptor after chronic
      theophylline treatment.

PMID- 7521499
TI  - Indications and timing for the bidirectional Glenn shunt versus the fenestrated
      Fontan circulation.

PMID- 7521498
TI  - Aprotinin in children undergoing correction of congenital heart defects. A double
      blind pilot study.
AB  - Thirty children undergoing surgical repair for congenital heart defects were
      randomly selected for a double-blind study on the anti-hemorrhagic and blood
      saving properties of aprotinin. The treatment group comprised 14 patients who
      received aprotinin 7 mg/kg of body weight until the end of perfusion. The placebo
      group (n = 16) received an infusion of the corresponding volumes of saline.
      Patients treated with aprotinin bled less during the operation (12.6 ml/kg versus
      18.1 ml/kg, p = 0.25) and in the first 24 postoperative hours (chest drainage
      12.1 ml/kg versus 17.7 ml/kg, p = 0.07). Hemoglobin loss into chest drainage was
      reduced in the treated group by half (0.66 versus 1.21 gm in 24 hours, p = 0.07).
      Fewer blood donors were needed during hospitalization by patients receiving
      aprotinin (1.07 versus 2.75 donors per patient, p = 0.04). Postoperative
      transfusion was unnecessary in 64.2% of patients receiving aprotinin compared
      with only 25% of the placebo group (p = 0.03). Aprotinin increased diuresis
      significantly during perfusion (4.3 ml/kg versus 1.0 ml/kg, p = 0.005). Other
      parameters are evaluated, and considerations are made regarding adequacy of the
      dosage regimen. The drug seems to be safe and easy to handle in children.

PMID- 7521501
TI  - Why so many operations for localised prostate cancer?

PMID- 7521500
TI  - Subendothelial nerve fibers in bovine mesenteric lymphatics: an ultrastructural
      and immunohistochemical study.
AB  - In the lymphatic vessels of man and most animals the nerve fibers are confined to
      the adventitia. However, immunohistochemical studies suggest that
      acetylcholinesterase-positive and monoamine-containing fibers reach as far as the
      endothelium in bovines. The aim of this study was to verify the presence of
      subendothelial nerve fibers by transmission electron microscopy (TEM) in bovine
      mesenteric lymphatics and to determine whether typical sensory neurotransmitters
      such as Substance P (SP) and calcitonin gene related peptide (CGRP) could be
      detected in these fibers. TEM revealed numerous unmyelinated nerve fibers in the
      subendothelial connective environment in close association with endothelial
      cells. Their axons were devoid of Schwann cell sheath on the endothelial side and
      contained small clear vesicles and large nerve fibers were demonstrated to be SP
      and CGRP-immunoreactive with mouse monoclonal antibodies against SP and rabbit
      polyclonal antibodies against CGRP. It is hypothesized that these fibers act as
      mechanoceptors capable of detecting intraluminal pressure and vessel wall tension
      variations and of locally releasing SP and CGRP. Since SP, potentiated by CGRP,
      is known to be a vasoconstrictor in lymphatics, we propose that the contraction
      of bovine mesenteric lymphatics may also be neurogenic.

PMID- 7521502
TI  - Acute respiratory insufficiency during doxorubicin, cyclophosphamide, and G-CSF
      therapy.

PMID- 7521503
TI  - Lack of voltage-dependent anion channel in human mitochondrial myopathies.

PMID- 7521504
TI  - Factors affecting size and configuration of neodymium:YAG (Nd:YAG) laser lesions
      in the prostate.
AB  - Laser surgery for benign prostatic hypertrophy is a clinical reality and a
      promising alternative to traditional transurethral electroresection of the
      prostatic adenoma (TURP). Current methods of laser prostatectomy involve
      coagulation of prostate tissue using a quartz side-firing fiber that redirects a
      Nd:YAG laser beam at 70-90 degrees most commonly by means of a metal reflector.
      In this communication we describe a method of tissue evaporation using a side
      firing fiber that avoids use of a metal reflector by means of internal
      reflection. It is relatively resistant to damage when coming in contact with
      tissue. By placing the fiber tip in direct contact with tissue, much larger
      lesions are created because of more efficient energy transfer resulting in rapid
      evaporation of tissue under water. In prostate surgery, this phenomenon of
      accelerated evaporation can be used to bloodlessly evaporate adenomatous tissue
      creating a defect that resembles that of a traditional TURP.

PMID- 7521506
TI  - Serum tenascin levels in chronic liver disease.
AB  - To evaluate the diagnostic significance of tenascin, the extracellular matrix
      glycoprotein in chronic liver disease, serum tenascin levels were measured by a
      newly developed ELISA in 21 patients with chronic persistent hepatitis, in 55
      with chronic active hepatitis, in 59 with liver cirrhosis, in 31 with
      hepatocellular carcinoma, in 26 with acute hepatitis and in 66 healthy subjects.
      The serum tenascin level was significantly elevated in the patients with chronic
      active hepatitis, liver cirrhosis, hepatocellular carcinoma, and acute hepatitis
      when compared with the healthy subjects (p < 0.001). The serum tenascin level
      also increased with increasing severity of chronic liver diseases. A significant
      correlation was observed between the serum tenascin levels and serum levels of
      various extracellular matrix proteins such as type III procollagen N
      aminoterminal peptide (PIIIP), laminin and the 7S domain of type IV collagen (p <
      0.001). A strong positive correlation was observed between the serum tenascin
      levels and histologic findings, particularly in the degree of hepatic fibrosis.
      This is the first report documenting serum tenascin level increases in patients
      with various chronic liver diseases. The measurement of the serum tenascin levels
      may provide additional information relevant to the study of connective tissue.

PMID- 7521507
TI  - Antigenicity and antigenic relatedness of the outer membrane proteins of Shigella
      species.
AB  - SDS-PAGE analysis of the outer membrane proteins (OMP) of Shigella dysenteriae,
      S. flexneri, S. boydii and S. sonnei showed similar profiles after isolation from
      Shigella species grown at 30, 37 and 42 degrees C. In S. dysenteriae there was a
      25 and a 17 kD polypeptide at 37 degrees C only, compared with the other two
      temperatures. In all four Shigella spp the major protein band was around 34-38
      kD. Antibodies raised in mice against formalinized bacteria gave a strong OMP
      specific response in both IgM and IgG classes, with IgG1 being the dominant
      subclass in all the species. Western blotting showed the major OMP to be the
      predominant antigen which was present in all the three temperatures tested. Cross
      reactivity studies of the antigenic OMP of Shigella revealed that the major
      protein around 38 kD was related in the four species. Biochemical analysis of the
      partially purified major OMP indicated it to be porin.

PMID- 7521505
TI  - Changes in receptor-mediated endocytosis in liver sinusoidal cells after partial
      hepatectomy in the rat.
AB  - Liver sinusoidal cells play an important role in host defense by clearing
      particulate matter and macromolecules from the circulation. In this study,
      receptor-mediated endocytosis in sinusoidal cells was examined in two-thirds
      hepatectomized rats using 125I-labeled formaldehyde-treated bovine serum albumin
      (fBSA) as an endocytable macromolecule. The liver-weight to body-weight ratio in
      hepatectomized rats returned to the control value 10 days after hepatectomy. The
      endocytotic index for fBSA in sinusoidal cells decreased significantly to 0.0210
      +/- 0.0017 (controls, 0.0598 +/- 0.0019) on the first day, then returned to the
      control level at 5 days (0.0554 +/- 0.0030). The changes in hepatic uptake for
      fBSA showed a similar time course of the endocytotic index. A transient increase
      in the uptake of fBSA per unit weight of liver of 22-39% above control occurred 2
      to 3 days after hepatectomy. In contrast to fBSA, the endocytotic index in
      hepatocytes evaluated with 125I-labeled asialofetuin reached the minimum level on
      the second day, and then recovered to the control level 10 days after
      hepatectomy. These results suggest that endocytosis of fBSA by sinusoidal cells
      decreases after hepatectomy and rapidly recovers to normal before the completion
      of liver regeneration, whereas endocytosis of asialofetuin by hepatocytes
      decreases following hepatic resection and returns to normal when regeneration is
      substantially complete.

PMID- 7521508
TI  - Monoclonal antibodies to spirosin of Yersinia enterocolitica and analysis of the
      localization of spirosome by use of them.
AB  - Two hybridomas producing monoclonal antibodies (MAbs) were prepared by fusing
      myeloma cells (Sp2/0-Ag14) with mouse spleen cells immunized with purified
      spirosin from Yersinia enterocolitica SYT-11-72 (YE72). The antibodies produced
      by them were designated MAbs-S5 and S27. They were IgG2a and IgG1, respectively,
      both with kappa light chains. MAbs-S5 and S27 reacted specifically with spirosin
      from YE72. On Western blotting after limited proteolysis with Staphylococcus
      aureus V8 protease, YE72 spirosin revealed peptide fragments of 35 and 37 kDa
      reacting markedly with MAb-S5, which suggested the presence of an antigenic
      determinant on these fragments. By cellular fractionation of YE72 and subsequent
      EIA and Western blot analysis, spirosome was shown to be present in the cytoplasm
      of YE72.

PMID- 7521509
TI  - Effective induction of human NK cells with OK-432 and further augmentation of
      their cytolytic function by rIL-2.
AB  - Low concentrations of exogenously added recombinant interleukin 2 (rIL-2) were
      able to augment OK-432-induced natural killer (NK) cell activity. This kind of
      augmenting effect depended on the dose of rIL-2 and manifested itself only in
      PBMC stimulated with OK-432 (OK-MC) followed by rIL-2; augmentation did not
      happen in the reverse order. The existence of CD16+/CD25+ (IL-2 receptor
      positive; IL-2R+) and CD57+/CD25+ double positive cells which possess NK cell
      surface markers in OK-MC markedly increased in a long-term culture (12 days). A
      strong positive correlation was observed between the IL-2-dependent augmentation
      of NK activity and the quantitative changes in cell populations that possessed NK
      cell phenotypes. Treatment of the day-12-OK-MC with monoclonal anti-CD56 antibody
      plus complement could almost completely abrogate the augmented NK cytotoxicity.
      Furthermore, this augmenting effect was detectable within 4 hr after addition of
      rIL-2 at single cell level, suggesting that the effect did not require NK cell's
      DNA synthesis. Thus it was suggested that OK-432 could promote and upregulate the
      expression of IL-2 receptor (CD25) on CD56+ NK cell populations. Moreover, it was
      considered that the interaction of low concentration rIL-2 with IL-2 receptors on
      OK-432-activated NK cells could augment their lytic function.

PMID- 7521511
TI  - Molecular and physical organization of highly repetitive, undermethylated DNA
      from Pennisetum glaucum.
AB  - A HaeIII monomer of a repetitive DNA family from Pennisetum glaucum (L.) R. Br.
      cv. Massue has been cloned and characterized. The repeat is 137 bp long and is
      organized in head-to-tail orientation in tandem arrays. The HaeIII monomer
      contains 55% A+T residues. The distribution of this highly repetitive sequence in
      different Pennisetum species and in other cereals was investigated. The HaeIII
      satellite is present in all Pennisetum species investigated but absent from other
      genera examined. In situ hybridization revealed a centromeric localization of
      this sequence on all seven chromosome pairs and indicated chromosome-specific
      differences in copy number. Methylation was investigated by comparative
      restriction enzyme analysis (MspI/HpaII) which showed a greater extent of
      methylation of the internal C of the enzyme recognition site 5'-CCGG. A South
      Western analysis, using an anti-methylcytosine antibody to examine the
      methylation status in P. glaucum confirmed that the sequence is not highly
      methylated.

PMID- 7521512
TI  - Protein kinase C mediates delayed inhibitory feedback regulation of human
      neurokinin type 1 receptor activation of phospholipase C in UC11 astrocytoma
      cells.
AB  - Human UC11 astrocytoma cells were used to investigate the role of protein kinase
      C (PKC) and other kinases in neurokinin (NK)1 receptor desensitization. The
      selective NK1 receptor agonist [Sar9,Met(O2)11]-substance P stimulated a biphasic
      accumulation of [3H]inositol phosphates ([3H]IPs) in the presence of 10 mM LiCl
      in cells that had been prelabeled with [3H]inositol. An initial rapid phase of
      [3H]IP accumulation during the first 1 min was followed by a slower sustained
      phase for up to 90 min. These results demonstrate that the human NK1 receptor
      desensitizes rapidly but only partially. The selective PKC inhibitor Ro31-8220
      did not prevent rapid NK1 receptor desensitization but after a longer incubation
      significantly potentiated human NK1 receptor agonist-stimulated accumulation of
      [3H]IPs. These results suggest that, although PKC does not mediate the process of
      rapid desensitization, it does have an inhibitory role at later times. This
      conclusion is supported by studies with staurosporine, phorbol dibutyrate, and
      the protein phosphatase inhibitor okadaic acid. Studies using AlF4-, an agent
      that can directly activate G proteins, and Ro31-8220 suggested that PKC can exert
      inhibitory effects 'downstream' of receptor activation, although
      immunoprecipitation of the G proteins alpha q/alpha 11 demonstrated that they do
      not undergo phosphorylation in UC11 cells and are unlikely to be the target of
      PKC-mediated inhibitory feedback. Delayed inhibitory feedback by PKC may be
      mediated by phosphorylation of phospholipase C, although an additional site of
      action on the NK1 receptor cannot be ruled out.

PMID- 7521514
TI  - Induction of kinetochore-positive micronuclei in human lymphocytes by the anti
      fungal drug griseofulvin.
AB  - Griseofulvin (GF) is a widely used antifungal drug for the treatment of
      superficial dermatomycoses. However, because GF is carcinogenic and teratogenic
      in animal models there is considerable concern regarding its clinical
      application. Further, it produces numerical chromosome aberrations in human
      lymphocytes and cell lines. There are conflicting reports on the ability of GF to
      induce structural chromosomal aberrations. Here, we show GF induces micronucleus
      formation both in isolated peripheral lymphocytes and lymphocytes from whole
      blood cultures. An antikinetochore antibody was used to distinguish micronuclei
      with acentric chromosome fragments (kinetochore-negative) and from those
      containing whole chromosomes (kinetochore-positive). The micronuclei formed were
      99% kinetochore-positive in isolated lymphocytes. In addition, GF was able to
      alter the cell cycle kinetics of lymphocytes, thereby increasing the percentage
      of triploid cells. We conclude that GF is a strong aneuploidy-inducing agent in
      peripheral human lymphocytes and produces effects at concentrations which should
      be detectable in the blood of persons undergoing therapy.

PMID- 7521513
TI  - Simultaneous activation of adenylyl cyclase and protein kinase C induces
      production of nitric oxide by vascular smooth muscle cells.
AB  - Rat aortic smooth muscle cells produced large quantities of nitric oxide (NO)
      after exposure to interleukin-1 beta, and this was depressed in the presence of
      the protein kinase C inhibitor bisindolylmaleimide. Intracellular cAMP levels
      were elevated mildly in cytokine-treated smooth muscle cells, and the presence of
      forskolin enhanced both the cAMP levels and NO production. Inhibition of
      GTP:cyclohydrolase I by 2,4-diamino-6-hydroxypyrimidine attenuated NO production
      by interleukin-1 beta-treated cells. GTP:cyclohydrolase is the regulatory enzyme
      for de novo tetrahydrobiopterin synthesis, and the latter is a required cofactor
      for NO synthase activity. Treatment of smooth muscle cells with forskolin induced
      GTP:cyclohydrolase mRNA expression, and simultaneous treatment of cells with
      forskolin and phorbol esters elicited NO production. Angiotensin II and arginine
      vasopressin, acknowledged agonists for protein kinase C, elicited production of
      NO by forskolin-treated smooth muscle cells. These observations confirm the
      importance of GTP:cyclohydrolase activity for NO production by cultured smooth
      muscle cells and implicate both adenylyl cyclase and protein kinase C in this
      process.

PMID- 7521510
TI  - The bacterial nucleoid revisited.
AB  - This review compares the results of different methods of investigating the
      morphology of nucleoids of bacteria grown under conditions favoring short
      generation times. We consider the evidence from fixed and stained specimens, from
      phase-contrast and fluorescence microscopy of growing bacteria, and from electron
      microscopy of whole as well as thinly sectioned ones. It is concluded that the
      nucleoid of growing cells is in a dynamic state: part of the chromatin is "pulled
      out" of the bulk of the nucleoid in order to be transcribed. This activity is
      performed by excrescences which extend far into the cytoplasm so as to reach the
      maximum of available ribosomes. Different means of fixation provide markedly
      different views of the texture of the DNA-containing plasm of the bulk of the
      nucleoid. Conventional chemical fixatives stabilize the cytoplasm of bacteria but
      not their protein-low chromatin. Uranyl acetate does cross-link the latter well
      but only if the cytoplasm has first been fixed conventionally. In the interval
      between the two fixations, the DNA arranges itself in liquid-crystalline form,
      supposedly because of loss of supercoiling. In stark contrast, cryofixation
      preserves bacterial chromatin in a finely granular form, believed to reflect its
      native strongly negatively supercoiled state. In dinoflagellates the DNA of their
      permanently visible chromosomes (also low in histone-like protein) is natively
      present as a liquid crystal. The arrangement of chromatin in Epulocystis
      fishelsoni, one of the largest known prokaryotes, is briefly described.

PMID- 7521515
TI  - Mutagenic and carcinogenic effects of waste oil of frying bean cake on
      Saccharomyces cerevisiae and Schizosaccharomyces pombe.
AB  - The present investigation was conducted to study the genotoxic effects of waste
      oil of frying bean cake (Taamiah oil) using Saccharomyces cerevisiae and
      Schizosaccharomyces pombe as test organisms. The results showed that the
      different concentrations of Taamiah oil exert different toxicity on yeast cells.
      the induced toxicity in both organisms was gradually increased with rising the
      concentration of Taamiah oil While, the differences between cellular survival and
      respiratory deficient mutants in treated and untreated samples were significant.
      Though Taamiah oil induced a concentration-dependent toxicity, it did not exert
      an induction of recombination. Thus, it seems likely that there was a cytotoxic
      effect and a weak effect on the induction of cytoplasmic petite mutations in
      yeast. The results suggest that Taamiah oil does not seem to induce lesions in
      DNA that are subject to excision repair. However, in Schizosaccharomyces pombe
      some point mutations seem to be induced in addition to toxicity. The conclusion
      is straight forward that waste oil of frying bean cake is mutagenic and may be
      carcinogenic in humans.

PMID- 7521516
TI  - Clastogenicity of lanthanides--induction of micronuclei in root tips of Vicia
      faba.
AB  - The clastogenic property of two lanthanides, Praseodymium and Neodymium, was
      evaluated by scoring the frequencies of micronucleated cells in the interphase
      and chromosome/chromatid aberrations at ana-telophases in root tips of Vicia faba
      L. The significant increase in the frequency of micronucleated cells coupled with
      the increase in the frequency of chromosome/chromatid bridges and lagging
      chromosomes/chromatids suggest that these two are clastogenic for Vicia faba root
      cells.

PMID- 7521517
TI  - In vitro and in vivo genotoxicity evaluation of hormonal drugs v. mestranol.
AB  - Genotoxicity of a widely used estrogen, Mestranol, was undertaken using in vitro,
      in vivo and host-mediated assay with bacteria as indicator organism. Analyses of
      chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes
      and chromosome aberrations, micronuclei and sister chromatid exchanges (SCEs) in
      bone-marrow cells of mice showed the drug to be capable of attacking the genetic
      material. However, both Ames Salmonella/S9 assay with and without S9 mix and host
      mediated assay using same tester strains of Salmonella, did not show any
      significant increase/decrease in the His+ revertants.

PMID- 7521518
TI  - In vivo studies of a crude extract of Phyllanthus amarus L. in modifying the
      genotoxicity induced in Vicia faba L. by tannery effluents.
AB  - The genotoxic effects of two types of tannery effluent (Raw-to-Wetblue and
      Wetblue-to-Finish) and the antigenotoxic property of a crude extract of
      Phyllanthus amarus L. were evaluated using the root meristem of Vicia faba L. as
      the in vivo test system. The root tip cells were exposed to the tannery effluents
      at different concentrations for varying durations. Squash preparations were made
      following Haematoxylin staining procedures. Cytological investigations revealed a
      duration- and concentration-dependent decrease in mitotic frequency and an
      increase in chromosomal irregularities. The root meristems pre-treated with
      effluents for 8 h (Raw-to-Wetblue) and 24 h (Wetblue-to-Finish) which caused the
      maximum incidence of mitotic anomalies, were then exposed to the crude extract of
      Phyllanthus amarus (0.25, 0.5, 0.75 and 1%) to study its efficacy modifying
      genetic damage. It was observed that the root meristems post-treated with
      Phyllanthus showed a significant reduction in the frequency of chromosomal
      alterations. However, there was no significant variation in the mitotic
      frequency. The study suggests that Phyllanthin, a principle of Phyllanthus
      amarus, is antigenotoxic.

PMID- 7521519
TI  - Mutagens in indoor air particulate.
AB  - Twenty-seven extracts of airborne particulate from domestic environments, both in
      the absence of sources of pollution and during activities such as smoking
      tobacco, using a fireplace, and cooking using grills and barbecues, and eight
      control samples of outdoor particulate were tested using the Salmonella/microsome
      assay on strains TA98 and TA98NR. Dust levels and mutagenic activity in the
      indoor environments turned out to be very low in the absence of polluting
      sources, with highest mean values in winter of less than 0.1 mg/m3 and 6 and 12
      revertants/m3, respectively without and with S9. The specific mutagenic activity
      of indoor dust ranged from 22 and 137 revertants/mg, with a contribution of
      nitroarene compounds of about 50%, indicating that, in city indoor air, the main
      cause of background particulate pollution is very probably penetration of traffic
      fumes from the outside. In contrast, in a country house far from traffic, very
      low dust and mutagenicity levels were found, without the influence of nitroarene
      compounds. The presence of autochthonous polluting sources, such as tobacco smoke
      and fumes from cooking and wood or charcoal burning, greatly increased indoor
      dust levels, especially during cooking operations, which reached 25.5 and 31.6
      mg/m3. The particulate produced by the various indoor pollution sources showed
      varying specific mutagenic activities. The highest values were found for fumes
      produced by burning charcoal and wood, smoking tobacco, and cooking foods with
      high animal protein contents. Mutagens responsible were mainly direct-acting in
      the case of fumes from burning wood or charcoal, and required mammalian metabolic
      activation in the case of fumes from tobacco and meat, with a lower contribution
      (maximum 33%) of nitroarenes than in urban particulate.

PMID- 7521520
TI  - Biomonitoring of nurses handling antineoplastic drugs.
AB  - The micronuclei analysis in exfoliated cells of the buccal cavity was employed in
      the cytogenetic monitoring of nurses handling antineoplastic drugs. The group
      under study consisted of 25 subjects who showed a marked increase in
      micronucleated cells as compared with the control group (Chi-square = 15.12, with
      one degree of freedom, P < 0.001).

PMID- 7521521
TI  - Role of chlorophyllin as an in vivo anticlastogen: protection against gamma
      radiation and chemical clastogens.
AB  - Chlorophyllin was evaluated in the mouse bone marrow micronucleus test for its
      possible protective effects against chromosomal damage induced by gamma
      radiation, cyclophosphamide, N-nitroso-N-ethylurea and urethane. Three doses of
      chlorophyllin (50, 100 and 200 mg/kg, b.w.) were orally administered to mice 2 h
      before exposure to the clastogens under investigation. The results obtained
      demonstrated that chlorophyllin can significantly reduce the incidence of
      micronucleated polychromatic erythrocytes induced by gamma-radiation (1.15 Gy)
      and all the three chemical clastogens. However with the exception of
      cyclophosphamide there was no indication of a dose response for the in vivo
      anticlastogenic effects of chlorophyllin.

PMID- 7521522
TI  - Effects of gamma-irradiation on the yield of mid-ventral white spots in mice in
      different genetic backgrounds and at different times during development.
AB  - Pregnant females C57BL/10JHir-p/p mice crossed with C57BL/10JHir males were whole
      body irradiated with a single acute dose of 60Co-gamma-rays to investigate the
      effect of gamma-radiation on embryonic melanoblasts. The effect was studied by
      scoring changes in the cutaneous coats of F1 offspring 25 days after birth. White
      spots were found in mid-ventrum of the animals. Melanoblasts and melanocytes were
      not observed in the spotted skin. The frequency of the spots increased in a dose
      dependent manner. White spots were found in mid-ventrum of (C57BL/6J female x
      C3H/HeJmsHir male) F1 exposed to gamma-rays. However, the frequency of the spots
      in (C57BL/6J female x C3H/HeJmsHir male) F1 were extremely lower than that in
      (C57BL/10JHir-p/p female x C57BL/10JHir male) F1, suggesting the possibility that
      the frequency of mid-ventral white spots are genetically controlled. Moreover,
      the highest frequency was found in (C57BL/10JHir-p/p female x C57BL/10JHir male)
      F1 irradiated at 8.5 days of gestation. This stage corresponds to the stage of
      initiation of neural-crest cell migration. These results indicate that gamma
      radiation affects the differentiation of melanocytes in the skin both with
      genetical control and with greater effects seen at the stage of initiation of
      neural-crest cell migration.

PMID- 7521523
TI  - In vivo expression and mitochondrial import of normal and mutated tRNA(thr) in
      Leishmania.
AB  - Evidence suggests that mitochondria of protozoans and plants contain nuclear
      encoded tRNAs. In trypanosomatids, the entire set of tRNAs in the mitochondria
      are presumably imported from the nucleus, but the mechanism of tRNA import is not
      presently understood. In this study, we have employed a plasmid-encoded nuclear
      tRNA gene as a means of investigating tRNA expression and mitochondrial import in
      vivo in Leishmania tarentolae. Using a Leishmania plasmid, we cloned a 1-kb or
      250-bp restriction fragment carrying the nuclear tRNA(thr) gene and three in
      vitro mutagenized derivatives: Tac6 (an insertion of 6 nucleotides at the
      anticodon loop), Td4 (a 4-nt insert at the D-loop) and Tv4 (a 4-nt insert at the
      variable arm). Leishmania cells stably transfected with these plasmids were then
      examined for tRNA expression and import by Northern analysis. The results show
      that the plasmid-encoded wild type tRNA(thr) gene produced a significantly
      elevated level of expression in the cytosol. Similarly, the Tac6-transfected
      cells exhibited a large abundance of the mutant RNA relative to the normal tRNA
      (chromosome-encoded gene transcripts) in the cytosol. Furthermore, the mutant
      Tac6 RNA was found imported into mitochondria, although the proportion of the
      mutant vs. normal tRNA in mitochondria was greatly reduced as compared to that in
      the cytosol. We suggest that the mitochondrial import machinery is capable of
      discriminating against the mutant RNA in favor of the normal tRNA for import. In
      another example, we found that the Tv4 gene showed expression, albeit somewhat
      reduced, but its import into mitochondria was completely blocked. Unexpectedly,
      the 4-base addition mutation (Td4) at the D-loop showed neither expression nor
      import. While these results clearly signify the importance of various segments
      within the tRNA gene for in vivo expression, our data underscore the significance
      of the variable loop for mitochondrial import. It is our belief that this plasmid
      encoded tRNA gene expression system in Leishmania may be useful in gaining
      further insights on tRNA import.

PMID- 7521524
TI  - Evidence for the existence of low-energy laser bioeffects on the nervous system.
AB  - The reported effects of low-energy laser irradiation on the nervous system are
      manifested in alterations in cellular and extracellular biochemical constituents
      and reactions, as well as in changes in cell division rates. These bioeffects
      were observed in both in vivo and in vitro experiments. Other observed phenomena
      relate to the function of the nervous system and consist mainly of induced
      alteration in electrical conduction, stimulation thresholds, and behavioral
      effects. Clinical aspects of low-energy laser bioeffects relate mainly to pain
      mitigation and postponement of the posttraumatic neural degeneration processes.
      Many of the reported observations were obtained by experiments apparently
      conducted according to less than rigorous scientific criteria, and some could not
      be duplicated. On the whole, however, there is little doubt that low-energy laser
      irradiation exerts some effects on the nervous system under specific conditions
      of irradiation and tissue exposure via a mechanism which is probably
      photochemical in nature.

PMID- 7521526
TI  - False positive latex agglutination test with Neisseria meningitidis ACYW135 in a
      patient with intracranial dermoid tumor.

PMID- 7521525
TI  - Local immune response in hyperplastic lesions of the larynx.
AB  - A retrospective morphologic and immunohistochemical study of 25 benign and 5
      malignant laryngeal hyperplastic lesions was performed concerning a local immune
      response which might be characteristic and of prognostic value for each
      particular group of these alterations, using Kambic's classification, especially
      for precancerous and cancerous lesions. On paraffin and frozen sections, 7
      monoclonal antibodies against various leukocytic antigens were used. CD43 and
      CD45RO T lymphocytes were the predominant cells in the infiltrates, and their
      frequency increased according to the degree of hyperplastic lesions. Next in
      frequency were CD4 cells, and a predominance of CD4 over CD8 cells was an obvious
      finding. The infiltration of CD68-, CD57-, and CD20-positive cells was generally
      weak. The intensity and composition of the local reaction in all cases of
      atypical hyperplasias was nearly identical, regardless of their subsequent
      behaviour. No apparent cytotoxic effects on the epithelial cells, either in
      precancerous or in cancerous lesions, were observed. Thus, the immunocompetent
      cells in the epithelial and stromal tissue are most likely not an effective
      defense in preventing hyperplastic lesions from becoming malignant. It seems that
      laryngeal hyperplastic lesions do not provoke an essential defense immune
      response, but the present local inflammatory reaction might be a constituent part
      of etiologically different inflammations which may lead to unfavorable lesions.

PMID- 7521527
TI  - tRNA-like structures in 10Sa RNAs of Mycoplasma capricolum and Bacillus subtilis.
AB  - The stable RNAs, whose sequences are homologous to 10Sa RNA of Escherichia coli,
      have been isolated from Mycoplasma capricolum and Bacillus subtilis, both
      belonging to the Gram-positive bacterial group. The total nucleotide sequences of
      the RNAs have been determined by partial RNA sequencing and DNA sequencing of
      their genes. A comparison of the sequences, together with those of other
      bacterial 10Sa RNAs so far known, has shown that the 5'- and 3'-end sequences are
      well conserved among species, while the central parts reveal little homologies.
      Unexpectedly, the conserved 5'- and 3'-regions can be folded in a common tRNA
      like structure containing an amino acid-acceptor stem and a T phi C-stem/loop.
      The 3'-terminal CCA sequence of B.subtilis 10Sa RNA is not encoded on the DNA,
      but is added after transcription. Furthermore, the RNA is aminoacylatable with
      alanine in vitro, and binds to the 70S ribosome in vivo.

PMID- 7521528
TI  - 'Race no more': an alternative approach to cloning the 5' end of transcripts.

PMID- 7521529
TI  - Viral hepatitis--1993: an update.

PMID- 7521530
TI  - Monophyletic origin of beta-division proteobacterial endosymbionts and their
      coevolution with insect trypanosomatid protozoa Blastocrithidia culicis and
      Crithidia spp.
AB  - Some trypanosomatid protozoa (order Kinetoplastida) are well known to harbor
      bacterial endosymbionts. Their phylogenetic positions and evolutionary
      relationships with the hosts were deduced by comparing the rRNA gene sequences.
      Earlier, we observed that these symbionts from three Crithidia spp. are identical
      and are closely related to Bordetella bronchiseptica. We have now sequenced the
      genes of another endosymbiont and the host protozoan Blastocrithidia culicis. The
      16S rRNA genes of the Blastocrithidia and Crithidia symbionts share approximately
      97% identity and form a distinct group, branching off the B. bronchiseptica
      lineage in the beta-division of Proteobacteria. Comparison of their secondary
      structures in the stem regions suggests compensatory mutations of the symbiont
      sequences, contributing to their biased base transitions from G to A and C to T.
      Two putative genes encoding tRNA(Ile) and tRNA(Ala) are highly conserved in the
      otherwise variable internal transcribed spacer region. Comparisons of the host
      rRNA gene sequences suggest that the symbiont-containing Crithidia and
      Blastocrithidia are more akin to each other than to other trypanosomatids. The
      evidence suggests that Blastocrithidia and Crithidia symbionts descend from a
      common ancestor, which had presumably entered an ancestral host and thence
      coevolved with it into different species. We therefore propose naming the
      symbionts Kinetoplastibacterium blastocrithidii and Kinetoplastibacterium
      crithidii.

PMID- 7521534
TI  - Changes in single symptoms and separate factors of the schizophrenic syndrome
      after treatment with risperidone or haloperidol.
AB  - Risperidone, a rather selective blocker of D-2 and 5-HT-2 receptors, was, in the
      doses 1 mg, 4 mg, 8 mg, 12 mg and 16 mg a day, compared to the rather selective D
      2 blocker haloperidol in the dose of 10 mg a day, in 88 chronic schizophrenic
      patients. After one week placebo wash-out, the patients were randomly assigned to
      one of the six treatment groups and the study was performed as a double blind
      parallel-group study for 8 weeks. In the present analysis, a special emphasis has
      been laid on the effects on single symptoms and separate factors in the
      schizophrenic syndrome. Overall, risperidone in a dose of 4 mg a day was
      comparable to haloperidol in a dose of 10 mg a day. Risperidone was found to have
      a curvilinear dose-response curve with an optimum effect of 4 mg day on the
      negative, anxious/depressive and cognitive factors and with an optimum effect of
      8 mg day on the positive and excited factors. While haloperidol had significant
      effects on the negative and anxious/depressive factors, risperidone had
      significant effects on all five factors - the positive, the negative, the
      excited, the anxious/depressive and the cognitive. The fact that the novel drug
      had significant effects on the cognitive factor might be of great importance as
      concerns the possibilities for rehabilitation of chronic schizophrenic patients.

PMID- 7521533
TI  - Atomic-level accuracy in simulations of large protein crystals.
AB  - Proper treatment of long-range Coulombic forces presents a major obstacle to
      providing realistic molecular dynamics simulations of macromolecules. Traditional
      approximations made to lessen computational cost ultimately lead to unrealistic
      behavior. The particle mesh Ewald method accommodates long-range Coulombic forces
      accurately and efficiently by use of fast Fourier transform techniques. We report
      a 1-ns simulation of bovine pancreatic trypsin inhibitor in a crystal unit cell
      using the particle mesh Ewald methodology. We find an rms backbone deviation from
      the x-ray structure (0.33 A) that is lower than that observed between bovine
      pancreatic trypsin inhibitor in different crystal forms and much lower than those
      of previous simulations. These results bridge the gap between structures obtained
      from molecular simulation and those from experiment.

PMID- 7521535
TI  - In search of T-cell progenitors in the human foetal liver.

PMID- 7521536
TI  - APO-1 (CD95) and Bcl-2: determinants of cell death in the human thymus.

PMID- 7521537
TI  - Supramaximal inhibition of cholecystokinin-induced pancreatic amylase release
      involves desensitization to cytoplasmic Ca2+.
AB  - BACKGROUND: Cholecystokinin (CCK) is a major stimulant of pancreatic enzyme
      secretion. The dose-response relationship for CCK-induced secretion is bell
      shaped, with a characteristic supramaximal inhibition. The mechanism for this
      inhibition has now been studied. METHODS: The kinetics of amylase release and the
      changes of the cytoplasmic Ca2+ concentration ([Ca2+]i) were recorded during
      stimulation of guinea-pig pancreatic acinar cells with different concentrations
      of cholecystokinin octapeptide (CCK-8) and the Ca2+ ionophore ionomycin. RESULTS:
      Individual cells reacted with [Ca2+]i oscillations at 10(-11)-10(-10) M CCK-8 and
      with an initial peak followed by a sustained suprabasal level at 10(-9)-10(-8) M
      of the agonist. The latter response was also seen in suspensions of acinar cells
      at all tested concentrations of CCK-8 and at 10(-6)-10(-5) M of ionomycin. With
      increases of extracellular Ca2+ from 0.5 to 5.0 mM there was a rise of [Ca2+]i
      during exposure to 10(-9)-10(-8) M CCK-8 or 10(-5) M ionomycin but a paradoxical
      decrease at lower concentrations of CCK-8 or ionomycin. A dose-dependent increase
      of amylase release was seen at CCK-8 concentrations from 10(-11) to 10(-9) M. At
      10(-9)-10(-8) M CCK-8 secretion was characterized by an initial peak followed by
      a sustained phase. Whereas the initial peak of secretion remained unaffected by
      increasing CCK-8 from 10(-9) to 10(-8) M, the sustained phase was inhibited
      (supramaximal inhibition). Increasing extracellular Ca2+ from 0.5 to 5.0 mM
      transiently enhanced secretion in response to 10(-9) M but lacked effect during
      supramaximal inhibition of secretion by 10(-8) M CCK-8. CONCLUSIONS: Both initial
      and sustained CCK-8-stimulated amylase release increase with [Ca2+]i. However,
      supramaximal inhibition of secretion was not due to a decrease of [Ca2+]i but was
      characterized by desensitization to the stimulatory effect of [Ca2+]i.

PMID- 7521531
TI  - Control of transcription processivity in phage lambda: Nus factors strengthen the
      termination-resistant state of RNA polymerase induced by N antiterminator.
AB  - During transcription of phage lambda early operons, the N gene product alters
      host RNA polymerase (RNAP) so that transcription proceeds through multiple stop
      signals. Here, we reproduce the essence of N activity with purified components in
      synthetic transcription units that contain lambda pL promoter and the N
      recognition site, nutL, followed by a variety of intrinsic terminators. We show
      that three host factors (NusA, NusE, and NusG) are essential for N to allow
      appreciable transcription through multiple terminators and that this persistent
      antitermination is stimulated by a fourth factor, NusB. Remarkably, in the
      absence of all four factors, N suppresses various terminators placed near the nut
      site. This basal antitermination activity of N is enhanced by NusA and is
      diminished by high salt and temperature. We postulate that N interacts with RNAP
      directly, inducing the termination-resistant state. While NusA facilitates this
      interaction, the other factors strengthen it sufficiently over time and distance
      so that RNAP bypasses multiple terminators. The dispensability of NusB for
      persistent antitermination in vitro, but not in vivo, raises the possibility that
      NusB performs two functions: it increases the stability of N antitermination
      complex and also counteracts an inhibitory factor in the cell.

PMID- 7521532
TI  - A small mitochondrial double-stranded (ds) RNA element associated with a
      hypovirulent strain of the chestnut blight fungus and ancestrally related to
      yeast cytoplasmic T and W dsRNAs.
AB  - A small double-stranded (ds) RNA element was isolated from a moderately
      hypovirulent strain of the chestnut blight fungus Cryphonectria parasitica
      (Murr.) Barr. from eastern New Jersey. Virulence was somewhat lower in the dsRNA
      containing strain than in a virulent dsRNA-free control strain, but colony
      morphology and sporulation levels were comparable. A library of cDNA clones was
      constructed, and overlapping clones representing the entire genome were
      sequenced. The 2728-bp dsRNA was considerably smaller than previously
      characterized C. parasitica dsRNAs, which are 12-13 kb and ancestrally related to
      the Potyviridae family of plant viruses. Sequence analysis revealed one large
      open reading frame, but only if mitochondrial codon usage (UGA = Trp) was
      invoked. Nuclease assays of purified mitochondria confirmed that the dsRNA was
      localized within mitochondria. Assuming mitochondrial translation, the deduced
      amino acid sequence had landmarks typical of RNA-dependent RNA polymerases.
      Alignments of the conserved regions indicate that this dsRNA is more closely
      related to yeast T and W dsRNAs and single-stranded RNA bacteriophages such as Q
      beta than to other hypovirulence-associated dsRNAs.

PMID- 7521538
TI  - Insulin like growth factor-1 and -2 and their role in the re-epithelialisation of
      wounds; interactions with insulin like growth factor binding protein type 1.
AB  - Insulin like growth factor (IGF) 1 and 2 which are present and actively
      synthesised in the wound fluid stimulate several cell types involved in the
      process of wound healing. To investigate the role of IGF-1 and 2 and in addition,
      the association between IGF and their carrier proteins, IGF binding proteins
      (IGFBP), we have used a newly established model for human wound healing in fresh
      biopsy material. Histological examination shows that IGF-1 stimulates efficient
      reepithelialisation of the wounds both alone and in the presence of recombinant
      IGFBP-1. In contrast, IGF-2 stimulates healing only when used in combination with
      IGFBP-1. These findings suggest that the two IGFs and their carrier proteins may
      function during different phases of wound healing and that both IGF-1 and 2 act
      as potent inducers of wound healing; this may have direct clinical implications.

PMID- 7521539
TI  - Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1.
AB  - As normal cells progress toward malignancy, they must switch to an angiogenic
      phenotype to attract the nourishing vasculature that they depend on for their
      growth. In cultured fibroblasts from Li-Fraumeni patients, this switch was found
      to coincide with loss of the wild-type allele of the p53 tumor suppressor gene
      and to be the result of reduced expression of thrombospondin-1 (TSP-1), a potent
      inhibitor of angiogenesis. Transfection assays revealed that p53 can stimulate
      the endogenous TSP-1 gene and positively regulate TSP-1 promoter sequences. These
      data indicate that, in fibroblasts, wild-type p53 inhibits angiogenesis through
      regulation of TSP-1 synthesis.

PMID- 7521540
TI  - Mutations in aquaporin-1 in phenotypically normal humans without functional CHIP
      water channels.
AB  - The gene aquaporin-1 encodes channel-forming integral protein (CHIP), a member of
      a large family of water transporters found throughout nature. Three rare
      individuals were identified who do not express CHIP-associated Colton blood group
      antigens and whose red cells exhibit low osmotic water permeabilities. Genomic
      DNA analyses demonstrated that two individuals were homozygous for different
      nonsense mutations (exon deletion or frameshift), and the third had a missense
      mutation encoding a nonfunctioning CHIP molecule. Surprisingly, none of the three
      suffers any apparent clinical consequence, which raises questions about the
      physiological importance of CHIP and implies that other mechanisms may compensate
      for its absence.

PMID- 7521542
TI  - Visceral protein response to enteral versus parenteral nutrition and sepsis in
      patients with trauma.
AB  - BACKGROUND: Sepsis and the route of nutrient administration are clearly related
      to visceral protein levels; however, the mechanisms and amount of influence are
      not completely defined. METHODS: Constitutive and acute-phase protein levels were
      measured on days 1, 4, 7, and 10 in 68 severely injured patients with abdominal
      trauma indexes of 15 or more randomized to enteral or parenteral feeding. Groups
      were matched for age, abdominal trauma index, injury severity score, and length
      of stay. RESULTS: Significantly higher levels of constitutive proteins and lower
      levels of acute-phase proteins were found in patients randomized to enteral
      feeding. Although some "hepatic protein reprioritization" appeared to be caused
      by nutrient route, this appeared only in the less severely injured patients. A
      more important factor in visceral protein levels is a reduction in septic
      morbidity associated with enteral feeding. CONCLUSIONS: Enteral feeding produces
      greater increase in constitutive proteins and greater decreases in acute-phase
      proteins after severe trauma primarily caused by reduced septic morbidity with
      enteral feeding.

PMID- 7521541
TI  - Involvement of nitric oxide in the elimination of a transient retinotectal
      projection in development.
AB  - The adult pattern of axonal connections from the eye to the brain arises during
      development through the refinement of a roughly ordered set of connections. In
      the chick visual system, refinement normally results in the loss of the
      ipsilateral retinotectal connections. Inhibition of nitric oxide synthesis
      reduced the loss of these transient connections. Because nitric oxide is
      expressed by tectal cells with which retinal axons connect and because reduction
      of nitric oxide synthesis by tectal cells resulted in a change in the connections
      of retinal axons, nitric oxide probably serves as a messenger from tectal cells
      back to retinal axons during development.

PMID- 7521543
TI  - Evaluation of Caralluma tuberculata pretreatment for the protection of rat
      gastric mucosa against toxic damage.
AB  - The ethanolic extract of Caralluma tuberculata N. E. Brown has been screened for
      its potential to protect gastric mucosa against the injuries caused by 80%
      ethanol, 0.2 M NaOH, hypertonic saline, and indomethacin. C. tuberculata at doses
      of 250, 500, and 1000 mg/kg body wt given 30 min before the necrotizing agents
      provided dose-dependent protection against the damage caused by all tested
      agents. The effects caused by ethanol were further investigated. Treatment of
      rats with 1 ml of 80% ethanol (gavage) was found to cause depletion of stomach
      wall mucus, to lower the concentrations of proteins, nucleic acids, and
      nonprotein sulfhydryl groups in the stomach wall, and to cause histopathological
      lesions, including necrosis, erosions, congestion, and hemorrhage, of the stomach
      wall. C. tuberculata treatment caused a dose-dependent protection against all
      these effects. In the same manner it affected malondialdehyde concentrations
      altered by ethanol treatment. C. tuberculata also offered protection against
      mucosal damage caused by indomethacin. The protective effects of C. tuberculata
      in addition to its effects on mucus production and nonprotein sulfhydryl
      concentration may be mediated through its free radical scavenging and
      prostaglandin inducing properties.

PMID- 7521544
TI  - Nitric oxide released by platelets inhibits neutrophil B2 integrin function
      following acute carbon monoxide poisoning.
AB  - Carbon monoxide (CO) poisoning has been reported to temporarily inhibit B2
      integrin adherence molecules on leukocytes in previous studies in a rat model.
      The aim of this study was to investigate the mechanism for this effect. Studies
      were conducted using blood obtained from rats after they were exposed to CO and
      also with blood cells exposed to CO in vitro. Initial investigations indicated
      that inhibition of neutrophil (polymorphonuclear leukocyte, PMN) B2 integrin
      function was linked to the platelets in blood, as the effect was resolved by
      decreasing platelet number before PMN adherence was tested. The platelet effect
      could also be shown by incubating either platelet-rich plasma or whole blood with
      CO in vitro. The effect of platelets was blocked by superoxide radicals and by NG
      nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase. These
      observations suggested that CO caused platelets to release NO, an agent known to
      inhibit the function of B2 integrins. The concentration of NO measured in
      suspensions of platelets from rats poisoned with CO according to the established
      model (exposure to 1000 ppm CO for 40 min and 3000 ppm CO for 20 min) was 47
      nmol/10(8) platelets, in contrast to only 0.3 nmol NO/10(8) platelets from
      control rats. Enhanced NO release occurred despite a 60% inhibition of NO
      synthase activity, assessed by measuring conversion of [14C]L-arginine to
      citrulline. Exposure to only 1000 ppm CO for 1 hr caused platelets to release 74
      nmol NO/10(8) platelets, and no inhibition of NO synthase occurred. Enhanced NO
      release, and inhibition of PMN adherence, did not occur after platelets were
      exposed to light from a quartz lamp to photodissociate CO from heme proteins. The
      data suggest that the NO flux from platelets increased when CO became bound to
      heme-containing platelet proteins, which normally scavage intraplatelet NO and
      thus prevent diffusion beyond the platelet membrane.

PMID- 7521545
TI  - Percutaneous absorption, dermatopharmacokinetics and related bio-transformation
      studies of carbaryl, lindane, malathion, and parathion in isolated perfused
      porcine skin.
AB  - The percutaneous absorption of topically applied pesticides is a primary route
      for systemic exposure and potential toxicity. The isolated perfused porcine skin
      flap (IPPSF) is an in vitro model for studying percutaneous absorption of
      xenobiotics as well as cutaneous metabolism and toxicity in an anatomically
      intact viable skin preparation. In the present studies, percutaneous absorption
      of four different pesticides, carbaryl (C), lindane (L), malathion (M), and
      parathion (P), was assessed topically in an ethanol vehicle. A 4-compartment
      pharmacokinetic model was utilized to model their absorption profile. The order
      of absorption was C > P > L > M for the 8-h experimental period, but C > L > P >
      M for a model-extrapolated 6-day prediction. Metabolism of C and P was also
      assessed by high performance liquid chromatography (HPLC). The HPLC results
      indicate a significant first-pass effect for both pesticides after topical
      application, with parathion being metabolized to paraoxon and para-nitrophenol
      and carbaryl to naphthol. In addition, comparison of the metabolic data of P with
      previous results underscores the difference between non-recirculating and
      recirculating IPPSF systems in xenobiotic metabolism studies.

PMID- 7521546
TI  - [The kallikrein-kinin system and blood plasma proteolysis inhibitors in various
      childhood nephropathies].
AB  - Activity of the kallikrein-kinin system and proteinase inhibitors were studied in
      blood plasma of children at various stages of tubulointerstitial nephritis,
      pyelonephritis and dysmetabolic nephropathy. Similar alterations in the
      activities of kallikrein-kinin system and in the rate of proteolysis inhibition
      were observed in tubulointerstitial nephritis and pyelonephritis. Supplementary
      demonstrations were obtained about development of inflammation in
      tubulointerstitial nephritis. Absence of the kallikrein-kinin system activation
      and a decrease in the alpha 2-macroglobulin content were detected in dysmetabolic
      nephropathy. Definite components of the kallikrein-kinin system and the
      proteolysis inhibitors may be used as indicators in differential diagnosis of
      tubulointerstitial nephritis and dysmetabolic nephropathy.

PMID- 7521547
TI  - [Natural proteinase inhibitors as a basis for creating new drugs].
AB  - Isolation of the proteinases inhibitors, available for medicinal purposes, was
      described, where the inhibitor of the Kunitz type was obtained from bovine
      pancreas and the inhibitor of the Bowman-Birk type from soybeans. Screening of
      the immobilization procedures was carried out, which enabled the authors to
      produce the polymeric conjugates of the proteinase inhibitors exhibiting the
      maximal rate of activity against pancreatic proteinases and granulocyte
      elastases. Pharmacokinetics of the proteinase inhibitors obtained was studied.
      High molecular derivatives of the inhibitors from the bovine pancreas circulated
      in rat blood in larger quantities and longer, their total clearance was 5 times
      than native inhibitor preparations. The preparations containing these inhibitors
      from bovine pancreas exhibited a high therapeutic efficiency in treatment of rats
      with hemorrhagic pancreatitis and acute liver failure in rabbits.

PMID- 7521548
TI  - [Microbial purine decomposition].
AB  - 27 microorganisms were tested for their ability to degrade extracellular purines
      as sole sources of carbon, nitrogen, and energy. Beside adenine, guanine,
      xanthine, hypoxanthine, and urate as free purine bases, this test included 5'
      AMP, 5'-GMP, 5'-XMP, and 5'-IMP, as well as DNA and RNA as purine compounds.
      Generally, only a limited number of microbial species was capable of metabolizing
      the substances named above. Compared to the other species, Paracoccus
      denitrificans showed the greatest substrate spectrum, including the free bases as
      well as the mononucleotides. However, the polymers DNA and RNA were not degraded.

PMID- 7521549
TI  - Selective interference with P protein binding to paramyxovirus nucleocapsids.
AB  - We previously observed that some anti-nucleoprotein monoclonal antibodies were
      able to displace P protein from Sendai virus (SV) nucleocapsid cores. The current
      work extends that observation by showing that such antibody-mediated P
      displacement is not unique to Sendai virus nucleocapsids, but can also occur with
      nucleocapsids of a related human respiratory pathogen. Anti-NP antibody prevents
      binding of SV P protein to nucleocapsids from human parainfluenza virus type 1
      (PIV1) or from SV. Antibody also prevents binding of PIV1 P protein to PIV1
      nucleocapsids, but not to SV nucleocapsids. We have also examined the
      stoichiometry of antibody interference with P binding, to determine how large a
      nucleocapsid region can be protected from P binding by a single antibody
      molecule. We found that approximately 40 antibody molecules per nucleocapsid
      complex can block attachment of most P protein. This indicates that a single
      antibody molecule can prevent P binding to a region representing about 65
      nucleoprotein monomers on the nucleocapsid core.

PMID- 7521550
TI  - A rapid method for the analysis of influenza virus genes: application to the
      reassortment of equine influenza virus genes.
AB  - We describe a rapid method for genetic characterisation of influenza virus genes
      using reverse transcription and amplification by polymerase chain reaction
      (RT/PCR) of all virus segments simultaneously (multiplex RT/PCR) using primers
      based on the conserved terminal sequences. The product has been shown to be
      suitable for determination of partial nucleotide sequences which can be used to
      search nucleotide sequence databases and rapidly map the genetic origin of each
      segment. We illustrate the use of the method by analysing genetic reassortment in
      H7N7 equine influenza viruses.

PMID- 7521552
TI  - [The clinico-pathogenetic significance of specific antigenemia in typhoid fever].

PMID- 7521551
TI  - [Antigen-binding lymphocytes to the Mycobacterium paratuberculosis antigen in
      Crohn's disease and nonspecific ulcerative colitis].

PMID- 7521554
TI  - [Experience with the epidemiological surveillance of legionellosis in Rostov
      Province].

PMID- 7521553
TI  - [The incorporation of the labelled precursors of macromolecular compounds into
      the cells of pathogenic and saprophytic mycobacteria in the presence of Desoxon
      1].

PMID- 7521556
TI  - Developmental dyscalculia in children: review of the literature and clinical
      validation.

PMID- 7521555
TI  - [The use of an immunoblotting method for the study of the specificity of the iron
      regulated proteins in meningococcus].

PMID- 7521557
TI  - Treatment approaches in dyslexia.

PMID- 7521558
TI  - Verbal information processing in dyslexia--data from a follow-up experiment of
      neuro-psychological aspects and EEG.

PMID- 7521559
TI  - Children with specific reading retardation--early determinants and long-term
      outcome.
AB  - In a prospective epidemiological longitudinal study of children (n = 399) from
      age 8 to 18 years, children with specific reading retardation (n = 37) were
      identified by the modified Research Diagnostic Criteria of ICD-10. The group with
      specific reading retardation was compared with a group with other specific
      developmental disorders (n = 62), a group of children with normal intelligence (n
      = 285) and a group of children with below average intelligence (n = 15). No
      correlation was found between reading retardation and pre- and perinatal
      complications. Children with reading retardation suffered from environment
      related stress factors in early childhood and adverse familial conditions at 8
      years and the educational level of the mother was significantly lower. The number
      of additional psychiatric symptoms was increased at ages 8, 13 and 18. Conduct
      disorders, in particular, were more frequent in children with specific reading
      retardation and the rate of juvenile delinquency was increased (25%). The non
      verbal intelligence remained constant between ages 8 and 13, and spelling
      performance developed parallel to the control group with normal intelligence.
      Only one out of three showed a significant improvement in spelling ability.

PMID- 7521560
TI  - [4-Aminopyridine induced histamine release and its antagonism by certain drugs].
AB  - 4-Aminopyridine (4-AP), a known potassium channel blocker, was shown to induce
      histamine release from mast cells in mice. After ip 4-AP 5 mg.kg-1 the histamine
      content increased in blood, but decreased in the lung tissue. Calcium antagonists
      nifedipine (NIF) 500 mg.kg-1 ig, TMB-8 300 mumol.L-1 in vitro and potassium
      channel opener minoxidil (MIN) 100 mg.kg-1 inhibited the histamine release
      induced by 4-AP from mouse peritoneal mast cells (PMC). These results provide
      evidence that potassium channels are present in mouse mast cell membranes and
      indicate that the mechanism of histamine release by 4-AP may be related to the
      potassium channel blocking effect. As the result of this effect, the calcium
      channels open and the Ca2+ influx to the mast cells increases, thus eliciting
      histamine release.

PMID- 7521562
TI  - Growth hormone-dependent insulin-like growth factor binding protein is a major
      determinant of bone mineral density in healthy men.
AB  - To establish the major determinants of bone mass, we assessed relationships
      between bone mineral density (BMD) and height, weight, body mass index (BMI),
      muscle strength, physical capacity (VO2max), body composition, serum
      concentrations of insulin-like growth factor I (IGF-I), growth hormone (GH), the
      GH-dependent IGF binding protein (IGFBP-3), testosterone, sex hormone binding
      globulin (SHBG), osteocalcin, and parathyroid hormone (PTH) in 38 healthy men
      between 25 and 59 years of age. Values of BMD at all sites (total body, lumbar
      spine, and hip) were strongly correlated with IGFBP-3 (r = 0.51-0.64, p < 0.001
      at all sites), and total-body BMD was also significantly correlated with IGF-I (r
      = 0.43, p = 0.01). BMD measurements of the total body and of the different sites
      of the hip were negatively correlated with age and positively with weight, BMI,
      muscle strength, VO2max, and fat-free weight. IGF-I and IGFBP-3 were both
      positively related to muscle strength and VO2max. In a stepwise forward multiple
      regression analysis, the best model was obtained for the femoral neck, where
      IGFBP-3, GH, PTH, age, IGF-I, and BMI explained 77% of the variation in BMD. The
      partial regression coefficients of IGFBP-3, PTH, and BMI were all positive,
      whereas age, GH, and IGF-I were negatively correlated with BMD. In summary, IGFBP
      3 correlated better with BMD than any other study parameter. The findings
      indicate that GH is of importance for bone mass and suggest that IGFBP-3 not only
      reflects the integrated GH secretion but also has a direct role in the endocrine
      regulation of bone metabolism.

PMID- 7521561
TI  - Studies on the regulation of insulin-like growth factor binding protein 3
      secretion in human osteosarcoma cells in vitro.
AB  - Previous studies demonstrated that insulin-like growth factors (IGFs) are
      important autocrine and paracrine mitogens for human bone cells in vitro and that
      IGF binding proteins (IGFBPs) are important regulators of the biologic actions of
      IGFs. Thus, the actions of IGFs may be determined not only by their
      concentrations but also by the type and amount of IGFBPs produced by human bone
      cells at a local site in bone. In this study, we sought to determine the effects
      of dexamethasone, 1,25-(OH)2D3, and parathyroid hormone (PTH) on the secretion of
      IGFBP-3 in human osteosarcoma cell lines. Serum-free cultures of low- and high
      alkaline phosphatase (ALP) SaOS-2, MG-63, and TE89 human osteosarcoma cells were
      treated for 24 or 48 h with the effectors and the conditioned media used for
      determination of IGFBP-3 using a radioimmunoassay. We report that (1) the basal
      rate of IGFBP-3 secretion (ng/mg cellular protein) was dependent upon cell type,
      with TE89 > low-ALP Saos-2 > MG-63 > high-ALP SaOS-2 cells, and did not correlate
      with either basal cell proliferation or basal cellular ALP activity; (2)
      dexamethasone (10(-12)-10(-7) M) inhibited IGFBP-3 secretion in a dose-dependent
      manner in low-ALP SaOS-2, MG-63, and TE89 cells but not in high-ALP SaOS-2 cells;
      (3) 1,25-(OH)2D3 (10(-11)-10(-8) M) stimulated IGFBP-3 secretion in a dose
      dependent manner in MG-63, low-ALP SaOS-2, and high-ALP SaOS-2 cells, and the
      coaddition of TGF-beta and 1,25-(OH)2D3 increased synergistically IGFBP-3
      secretion and cellular ALP activity in MG-63 cells; and (4) human PTH-(1-34) (0.1
      100 ng/ml) had no significant effect on IGFBP-3 secretion in MG-63, low-ALP SaOS
      2, or high-ALP SaOS-2 cells. We conclude that such agents as dexamethasone, 1,25
      (OH)2D3, and PTH differentially regulate IGFBP-3 secretion in human osteosarcoma
      cells in vitro.

PMID- 7521564
TI  - Resuscitation of dogs from endotoxic shock by continuous dextran infusion with
      and without perflubron added.

PMID- 7521563
TI  - [The clinical and prognostic value of inversion of the PSA/PAP ratio in prostatic
      cancer].
AB  - The inversion of PSA/PAP ratio is not common in patients with prostate cancer. Of
      215 patients, 7 showed PSA levels below those of PAP (3.2%). All patients had
      metastatic disease at the time of diagnosis, 57% in multiple organs and tissues,
      with a Gleason value in all cases 4. Forty-three percent showed no early response
      to hormone therapy; mean survival interval recorded in these 7 patients was 21
      months. Such a situation may suggest a poor prognosis for this neoplasia.

PMID- 7521565
TI  - "Upstream" modification of vasoconstrictor responses in rat epigastric artery
      supplying an implanted tumour.

PMID- 7521566
TI  - Increased capillary segment length in cerebral cortical microvessels of rats
      exposed to 3 weeks of hypobaric hypoxia.

PMID- 7521567
TI  - Influence of DPPE on histamine release from isolated rat mast cells.
AB  - A second messenger function for histamine has been proposed based on the effects
      of the anti-estrogen drug DPPE (N,N-diethyl-2-(4-(phenylmethyl)phenoxy)
      ethanamine.HCl). The ability of DPPE to inhibit concanavalin A-induced histamine
      release led to the present investigation of its influence on the mast cell
      response to a wider selection of secretagogues. DPPE was an efficient inhibitor
      of antigen-induced release, while responses to compound 48/80 were virtually
      unaffected. Responses to the ionophore A23187 could be enhanced as well as
      inhibited, whereas the influence of DPPE on the combination of the ionophore and
      the phorbol ester TPA was variable and small. These results seem to exclude an
      involvement of a DPPE-sensitive histamine-mediated signal system of common
      importance in mast cell histamine release.

PMID- 7521568
TI  - Inhibitory effect of DS-4574, a peptidoleukotriene antagonist with mast cell
      stabilizing action, on compound 48/80-induced gastric mucosal lesions in rats.
AB  - We evaluated the inhibitory effect of DS-4574, a peptidoleukotriene antagonist
      with mast cell stabilizing action, on rat gastric mucosal lesions induced by
      compound 48/80 (C48/80: a mast cell degranulator), in comparison with those of
      disodium cromoglycate (DSCG: a mast cell stabilizer), LY171883 (a
      peptidoleukotriene antagonist) and cimetidine (a histamine H2 receptor
      antagonist). Subcutaneous administration of C48/80 (1 mg/kg) once daily for four
      consecutive days produced extensive gastric lesions in the fundic mucosa. DS-4574
      (20, 50 and 100 mg/kg/day, oral) and DSCG (200 mg/kg/day, intraperitoneal)
      treatment markedly inhibited formation of these mucosal lesions, but LY171883
      (100 and 200 mg/kg/day, oral) and cimetidine (400 mg/kg/day, oral) treatment did
      not. Moreover, DS-4574 and DSCG significantly suppressed both hyperhistaminemia
      and histamine release from rat peritoneal mast cells induced by C48/80. These
      results indicate that the inhibitory effect of DS-4574 on gastric lesions induced
      by C48/80 may be related to its mast cell stabilizing action, but to neither its
      antisecretory nor its peptidoleukotriene antagonistic activity.

PMID- 7521571
TI  - Treatment of hepatitis C infection: unraveling the mystery.

PMID- 7521569
TI  - Enhanced tissue responsiveness in colonic ion transport of cow's milk-sensitized
      guinea pigs.
AB  - The effects of leukotriene D4 (LTD4) on ion transport were investigated in
      submucosa/mucosa colonic segments from guinea pigs sensitized to cow's milk and
      in age-matched, non-immune animals. Mediators released from mast cells in immune
      animals challenged with beta-lactoglobulin evoked an increase in short-circuit
      current that was reduced by SK&F 102922, a peptidoleukotriene antagonist. Serosal
      addition of LTD4 (0.15-1 microM) evoked a concentration-dependent, bumetanide
      sensitive increase in short-circuit current which was greater in immune than non
      immune controls. In the absence of ongoing neural activity, 1 microM LTD4 evoked
      an 8-20 microA/cm2 increase in short-circuit current which was increased 8-13
      fold when ongoing neural activity was present. In tissues with ongoing activity,
      the response to 0.15 microM LTD4 was reduced by SK&F 102922, tetrodotoxin and
      atropine. LTD4 enhanced the responsiveness of the tissue to carbachol by a factor
      of two, but did not affect responses of T84 colonic epithelial cell monolayers to
      this agent. These results show enhanced secretory function for LTD4 in animals
      with allergy to cow's milk. They suggest that the level of ongoing neural
      activity in the enteric neural microcircuits is one of the major determinants of
      colonic secretory capacity.

PMID- 7521572
TI  - Retreatment of chronic hepatitis C with interferon.
AB  - OBJECTIVE: We analyzed the retreatment of chronic hepatitis C with interferon to
      get the standpoint for the selection of patients to receive it. METHODS: A
      complete response was defined as continuous normalization of the serum alanine
      aminotransferase (ALT) level and continuous disappearance of serum hepatitis C
      virus RNA (HCV-RNA) during interferon administration and more than 6 months
      after. Patients without complete response were classified as noncomplete
      responders. From August 1990 to May 1993, we retreated 23 noncomplete responders
      on initial treatment with interferon and studied the factors that alter the
      effectiveness. RESULTS: Complete response was achieved in eight (34.8%) patients;
      the other 15 patients did not achieve this degree of response. Three patients
      were of genotype II and five were of genotype III in these eight complete
      responders. All complete responders were patients with relapse who had had
      normalized serum ALT levels during the initial administration and undetectable
      HCV-RNA at the end of the period. No patient who failed to achieve normalization
      of the serum ALT level on initial treatment achieved a complete response on
      retreatment. HCV-RNA concentrations before retreatment were significantly less
      than before initial treatment in the eight complete responders. CONCLUSION:
      Interferon retreatment of patients who do not achieve a complete response may be
      effective in relapsed cases with undetectable HCV-RNA at the end of initial
      treatment. Selection of patients to receive interferon retreatment requires
      careful review and consideration of genotype, HCV-RNA concentration, and the
      clinical response on initial treatment.

PMID- 7521570
TI  - Potentiation of histamine release from human leucocytes by PAF.
AB  - Studies on the effects of PAF on histamine release from human leucocytes have
      yielded conflicting results. We therefore investigated the effects of PAF on
      leucocytic histamine release (HR) focusing on direct as well as on modulating
      effects. Peripheral blood leucocytes of normal and atopic subjects were incubated
      with PAF, anti-IgE and FMP for 30 min at 37 degrees C, and histamine was measured
      fluorometrically. Unlike anti-IgE (1/2000) and FMP (10(-5) M) which caused
      histamine release (HR) of 34 +/- 7% and 31 +/- 8%, respectively, PAF by itself
      (10(-11)-10(-5) M) failed to induce any significant HR from human leucocytes (<
      3%) in normal (n = 14) and atopic subjects (n = 6). Nevertheless, in normals as
      well as atopics, PAF, but not lyso-PAF, enhanced anti-IgE (1/2000) and FMP (10(
      5) M)-induced HR in a concentration-related manner. Maximal potentiation of
      histamine release caused by FMP and anti-IgE was achieved with PAF (10(-7)) (mean
      +/- SEM: 26 +/- 5%, n = 5, p < 0.01) and PAF (10(-5)) (mean +/- SEM: 20 +/- 7%, n
      = 7, p < 0.05), respectively. This potentiation was suppressed by WEB2086 (10(-5)
      M), a specific PAF antagonist. The time course of the enhancing effect produced
      by PAF was dependent on the type of secretagogue. The enhancement was nearly
      maximal when PAF and FMP were added simultaneously to the leucocytes, whereas a
      preincubation of 20 min with PAF was required to get maximal enhancement with
      anti-IgE. The enhancing activity of PAF on HR induced by both anti-IgE and FMP
      was reversed by washing the cells after preincubation. While PAF enhancement of
      FMP-induced HR persisted on mononuclear cell fraction containing basophils, that
      of anti-IgE-induced HR was considerably reduced under these conditions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7521573
TI  - Coated and uncoated self-expanding metal stents for malignant stenosis in the
      upper GI tract: preliminary clinical experiences with Wallstents.
AB  - OBJECTIVES: The clinical feasibility of self-expanding metal stents with respect
      to the technical success, complications, and reintervention rate should be
      tested. METHODS: Five coated and 26 uncoated prototype Wallstents, especially
      designed for stenosis of the upper GI tract, were implanted in 23 patients. All
      patients with dysphagia suffered from inoperable tumor stenosis of the esophagus
      or the cardia. Stent implantation was performed under slight i.v. sedoanalgesia.
      RESULTS: Technical success was achieved in all 31 implanted stents. Forty-eight
      hr after implantation, dysphagia was improved in 21/23 patients. Acute problems
      observed within 1 wk were stent migration (1 patient, uncoated stent), oblique
      position of the stent (3 patients), epigastric or retrosternal pain (9 patients),
      insufficient stent expansion (4 patients), and pouch formation at the upper rim
      of the stent (4 patients). An uncomplicated follow-up (median 66 days, range 10
      139 days) was seen in 12 patients (52%). Major problems in the follow-up period
      were stent migration in three patients (three coated stents, two stent migrations
      in one patient) and stent obstruction by tumor ingrowth/overgrowth and/or food
      impaction in eight patients (35%). Most of these problems could be successfully
      resolved by implantation of a second stent or electrocoagulation of overgrowing
      tumor tissue. By the 1st of March, 1994, three patients were still alive with a
      follow-up period of 530 days (median range, 336-880 days); 20 patients were
      decreased with a follow-up period of 70 days (median range, 3-374 days).
      CONCLUSIONS: Implantation of esophageal Wallstents is safe and has a low risk of
      acute complications and mortality for the patient. Early complications such as
      perforation and bleeding did not occur. Tumor ingrowth/overgrowth are the major
      reasons for the high reintervention rate in the follow-up period. Coated stents
      can resolve this problem, provided that stent migration can be avoided by
      improvement of the coating technology.

PMID- 7521574
TI  - How do you choose the size of the surgical margin for nonpalpable early gastric
      cancer?

PMID- 7521575
TI  - Healing of broken human chromosomes by the addition of telomeric repeats.
AB  - We have characterized and compared a series of naturally occurring chromosomal
      truncations involving the terminal region of the short arm of human chromosome 16
      (16p13.3). All six broken chromosomes appear to have been stabilized by the
      direct addition of telomeric repeats (TTAGGG)n to nontelomeric DNA. In five of
      the six chromosomes, sequence analysis shows that the three of four nucleotides
      preceding the point of telomere addition are complementary to and in phase with
      the putative RNA template of human telomerase. Otherwise we have found no common
      structural features around the breakpoint regions. These findings, together with
      previously reported in vitro data, suggest that chromosome-healing events in man
      can be mediated by telomerase and that a small region of complementarity to the
      RNA template of telomerase at the end of a broken chromosome may be sufficient to
      prime healing in vivo.

PMID- 7521576
TI  - Extent of vascularization as a prognostic indicator in thin (< 0.76 mm) malignant
      melanomas.
AB  - Angiogenesis in malignant melanoma (MM) was evaluated by comparing mean vessel
      number (MVN) in Spitz's nevi (SN), thick and thin MMs that metastasized, and
      thick and thin MMs with > or = 10-year survival. Vessels were identified with
      antibodies against factor VIII-related antigen (FVIII) and CD34 in 37 MMs (17 <
      or = 1.9 mm and 20 > or = 4.0 mm) with > or = 10-year follow-up and 10 SN from
      children (< or = 9 years old). Fields (x250) with the highest vessel density were
      counted by independent observers blinded to clinical outcome. There were no
      differences in MVN between SN versus MMs (P = 1.0), but the distribution of
      vessels was much more uniform in SN. Seven MM pairs (> or = 5.5 mm) and five
      pairs (< or = 0.75 mm) were matched by sex, age, site, stage, and primary
      treatment (paired t-test). In the pairs > or = 5.5 mm, there was no correlation
      with MVN with either metastasis or death (FVIII P = 0.98; CD34 P = 0.85). Among
      the thin paired lesions, high MVN (FVIII = 46, CD34 = 39) was significantly
      related not only to metastasis (FVIII P = 0.04, CD34 P = 0.03) but also to death
      (FVIII P = 0.04, CD34 P = 0.05). MVN does not separate SN versus MM nor predict
      outcome in thick (> or = 4.0 mm) MMs; however, high MVN (> or = 42 average) is
      predictive of metastasis and death in MMs < or = 0.75 mm. Larger matched studies
      are indicated to confirm this observation.

PMID- 7521577
TI  - Vascular endothelial growth factor/vascular permeability factor is temporally and
      spatially correlated with ocular angiogenesis in a primate model.
AB  - Ischemia often precedes neovascularization. In ocular neovascularization, such as
      occurs in diabetic retinopathy, a diffusible angiogenic factor has been
      postulated to be produced by ischemic retina and to lead to neovascularization of
      the retina, optic nerve, or iris. However, no angiogenic factor has been
      conclusively identified that satisfies this hypothesis. Vascular endothelial
      growth factor/vascular permeability factor, hereafter referred to as VEGF, is a
      likely candidate for an ocular angiogenic factor because it is a secreted
      mitogen, specific for endothelial cells, and is upregulated by hypoxia. We
      investigated the association of VEGF with the development of experimental iris
      neovascularization in the cynomolgus monkey. Following the production of retinal
      ischemia by laser occlusion of all branch retinal veins, VEGF was increased in
      the aqueous fluid, and the aqueous VEGF levels changed synchronously and
      proportionally with the severity of iris neovascularization. Northern analysis
      and in situ hybridization revealed that VEGF messenger RNA is upregulated in the
      ischemic retina. These observations support the hypothesis that ocular
      neovascularization is regulated by a diffusible factor and identify VEGF as a
      likely candidate for a retina-derived vascular permeability and angiogenesis
      factor in vivo.

PMID- 7521580
TI  - Relative quantification of angiotensin-converting enzyme mRNA in human smooth
      muscle cells, monocytes, and lymphocytes by the polymerase chain reaction.
AB  - A method was developed for relative quantification of angiotensin-converting
      enzyme (ACE) mRNA in as few as 100 cells. After reverse transcription of total
      RNA to cDNA, multiplexed polymerase chain reaction with two sets of primers
      amplified ACE cDNA and that of an internal standard glyceraldehyde phosphate
      dehydrogenase (GAPDH) simultaneously. By adjusting primer pair concentrations,
      both ACE and GAPDH were amplified with constant efficiencies. Macrophage-like
      U937 histiocytic lymphoma cells expressed ACE mRNA constitutively. Freshly
      isolated human monocytes did not express ACE mRNA initially, but after 4 days in
      culture had 8% of the amount found in U937 cells. After phorbol ester
      stimulation, monocytes transcribed ACE at levels comparable to U937 cells. Human
      smooth muscle cells had ninefold more ACE mRNA than 4-day monocytes, but 30% less
      than U937 cells. In contrast, a mixed population of lymphocytes was devoid of ACE
      mRNA.

PMID- 7521578
TI  - Murine pancreatic ductal adenocarcinoma produced by in vitro transduction of
      polyoma middle T oncogene into the islets of Langerhans.
AB  - Pancreatic islets isolated from juvenile but not aging adult mice, when infected
      with a retrovirus carrying polyomavirus middle T oncogene, produced cell lines,
      mPAC, with characteristics both of pancreatic ductal epithelium and
      neuroendocrine cells of the islets. Following three cycles of single cell
      cloning, mPAC cells consisted of two subtypes, a null cell, and a double-positive
      cell that co-expressed cytokeratin, a marker of ductal epithelium, and A2B5, a
      neuroendocrine ganglioside expressed in developing islet cells. Two islet cell
      genes, encoding somatostatin and pancreatic polypeptide, were transcribed at low
      levels in most mPAC clones, whereas the insulin and glucagon genes were not. Upon
      inoculation of mice, mPAC cells rapidly formed well-differentiated ductal
      adenocarcinomas that expressed cytokeratin but not the islet cell markers. The
      mPAC phenotype may result from a specific dedifferentiation of juvenile islet
      cells or ductal epithelium induced by middle T protein. Alternatively, mPAC cells
      may arise by transformation of a multipotential progenitor present within or in
      juxtaposition to juvenile islets. This cell type could therefore represent one of
      the targets in human cancers of the pancreatic duct. Moreover, signal
      transduction systems modulated by middle T, including src-related kinases,
      phosphatidylinositol kinase, and protein phosphatase 2A, may be involved in
      pancreatic carcinogenesis.

PMID- 7521579
TI  - Primary cultures of rat islet capillary endothelial cells. Constitutive and
      cytokine-inducible macrophagelike nitric oxide synthases are expressed and
      activities regulated by glucose concentration.
AB  - We have succeeded in obtaining cultures of pure rat islet capillary endothelial
      cells. These multiply in vitro and exhibit the same antigenic phenotype as
      expressed in situ: von Willebrand factorhigh, Ox43 (rat endothelial marker)weak,
      and Ox2 (thymocyte and brain endothelium marker)high. This phenotype differs from
      both exocrine endothelium stained in situ and rat aorta endothelial cells
      cultured in vitro under identical conditions. Islet and aorta endothelial cells
      were cultured in the presence of various glucose concentrations. Nitrite and
      citrulline concentrations in culture supernatants were measured as an indirect
      quantification of nitric oxide formation. In islet endothelia, both nitrite and
      citrulline levels were found to be strongly glucose-dependent, with high levels
      at high glucose concentrations and vice versa, in contrast to aorta endothelial
      cells, where no glucose effect was found. Shifting islet endothelial cultures
      from high to low glucose levels or the reverse led to a slow decrease or increase
      in nitrite and citrulline formation with several cell generations needed to reach
      steady levels. Adding a combination of the cytokines interleukin-1 beta, tumor
      necrosis factor-alpha, and interferon-gamma to both endothelial cell cultures led
      to a dramatic increase of nitric oxide formation. Again with islet but not with
      aorta endothelial cells a modulating effect by glucose concentrations was found.
      Reverse-transcription-polymerase chain reaction with specific primers
      demonstrated the presence of constitutively expressed nitric oxide synthase-RNA
      in the islet capillary endothelial cells and confirmed the glucose effect. In
      addition, we found that cytokines indeed induce the expression of inducible
      synthase messenger RNA in both endothelial cells, which was not found in the
      absence of cytokines. Electron paramagnetic resonance spectroscopy of islet
      endothelial cells confirmed intracellular synthesis of nitric oxide in the
      presence of cytokines. In conclusion, we here for the first time provide evidence
      that constitutive nitric oxide synthase is also expressed in capillary
      endothelium and that cytokine challenge leads to the expression of the inducible
      isoform in these cells.

PMID- 7521584
TI  - [Editorial symposium: Palliative treatment for esophageal cancer].

PMID- 7521583
TI  - [Intensive intralymphatic and lymphotropic therapy in children].
AB  - Study of the effect of endolymphatic therapy with antibiotics and antioxidants on
      lipid peroxidation and endotoxicosis level in children in critical state showed
      that endolymphatic infusion of nonenzymatic antioxidants (vitamin E, unithiol)
      and wide-spectrum antibiotics noticeably reduced the activity of free-radical
      lipid peroxidation and accelerated detoxication in comparison with the control
      group.

PMID- 7521581
TI  - The detection of phospholipase-resistant and -sensitive glycosyl
      phosphatidylinositol membrane anchors by western blotting.
AB  - Glycosyl-phosphatidylinositol (GPI) membrane anchors are present on a large
      number of eukaryotic plasma membrane proteins. Some of these anchors can be
      cleaved with bacterial phosphatidylinositol-specific phospholipases C, and a
      glycosyl-phosphatidylinositol-specific phospholipase C from Trypanosoma brucei,
      to reveal an epitope called the cross-reacting determinant. Other glycosyl
      phosphatidylinositol anchors are resistant to the action of these enzymes prior
      to treatment with mild base. A simple method is described for identifying both
      phospholipase-sensitive and -resistant anchors using anti-cross-reacting
      determinant antibodies on Western blots. This procedure represents a high
      sensitivity general method for the identification of GPI-anchored proteins.

PMID- 7521582
TI  - [Evaluation of adequate heparinization during artificial circulation in the
      framework of prolonged intraoperative administration of high doses of aprotinin].
AB  - The aim of this research was to evaluate the effect of high aprotinin doses on
      activated coagulation time (ACT) in patients with aortocoronary bypass. A total
      of 100 patients were examined. All of them were administered in a double blind
      test either aprotinin or placebo in standard doses. Our results permit a
      conclusion that adequate heparinization during aprotinin therapy can be achieved
      at ACT values more than 750 sec and protamine sulphate dose should be estimated
      from initially administered heparin dose. With ACT values exceeding twofold the
      usual ones there was no evidence of excessive heparinization leading to marked
      thrombocytopenia and bleeding.

PMID- 7521585
TI  - [Current findings in the palliative therapy of esophageal cancer. Introduction
      and general considerations].

PMID- 7521586
TI  - [The indications for palliation in esophageal cancer].

PMID- 7521587
TI  - [Dilatations].

PMID- 7521588
TI  - [Prostheses].

PMID- 7521590
TI  - [Tube feeding].

PMID- 7521589
TI  - [Metal prostheses].

PMID- 7521591
TI  - [The endoscopic palliation with the Nd:Yag laser of advanced esophageal tumors:
      the results and survival].

PMID- 7521592
TI  - [Photodynamic therapy in the palliation of esophageal tumors].

PMID- 7521593
TI  - [Bipolar coagulation in the palliation of malignant dysphagia].

PMID- 7521594
TI  - [The endoscopic palliation of recurrences on esophageal anastomoses].

PMID- 7521595
TI  - [The special uses of esophageal prostheses: pharyngoesophageal prostheses].

PMID- 7521597
TI  - [The palliative surgery of esophageal cancer].

PMID- 7521596
TI  - [The special uses of esophageal prostheses: the treatment of malignant fistulae].

PMID- 7521598
TI  - [The role of endoluminal curietherapy in the treatment of esophageal carcinoma].

PMID- 7521599
TI  - [The indications for and results of palliative treatment in patients with
      esophageal and cardial carcinomas].

PMID- 7521600
TI  - Induction of protective immunity using minigenes.

PMID- 7521601
TI  - Clinical use of hematopoietic growth factors for control of infections after high
      dose chemotherapy.
AB  - Hematopoietic growth factors are being used to accelerate the recovery of
      myelopoiesis following high-dose chemotherapy in cancer patients. G-CSF and GM
      CSF reduce the duration of neutropenia following chemotherapy. Rapid restoration
      of neutrophils has been associated with reduced incidence of neutropenic fever
      and documented infections and fewer days of intravenous antibiotics and
      hospitalization. Recent studies suggest that combinations of cytokines may
      further expand the hematopoietic cell populations, which may be particularly
      useful following myeloablative chemotherapy, when thrombocytopenia may be a dose
      limiting toxicity. For example, IL-3, which stimulates early progenitor cells,
      has definite but inconsistent effects on increasing neutrophil and platelet
      counts. However, in combination with later-acting cytokines (e.g., GM-CSF and IL
      6), recovery from both thrombocytopenia and neutropenia is accelerated. As dose
      escalation of chemotherapy becomes more widely practiced, the role of cytokine
      combinations will become increasingly important.

PMID- 7521602
TI  - mRNA subtractive hybridization for the isolation and identification of tissue
      culture-induced determinants from Haemophilus influenzae biogroup aegyptius, the
      causative agent of Brazilian purpuric fever.

PMID- 7521603
TI  - Nitric oxide has an immunoregulatory role other than antimicrobial activity in
      Legionella pneumophila infected macrophages.

PMID- 7521605
TI  - Cross-reactive protection eliciting epitopes of pneumococcal surface protein A.

PMID- 7521604
TI  - Role of porins from Salmonella typhi in the induction of protective immunity.

PMID- 7521606
TI  - Palliative care in Singapore--good medicine given with compassion.

PMID- 7521607
TI  - Management of intestinal obstruction in patients with advanced cancer.
AB  - Intestinal obstruction is a common and distressing complication for patients with
      advanced abdominal or pelvic cancer. Palliative surgery has an inevitable high
      mortality and morbidity rate in these patients who are often very ill.
      Conservative treatment, using intravenous fluids and nasogastric suction, has not
      been shown to cause resolution of the obstruction and it involves
      hospitalisation, immobility and discomfort. Pharmacological treatment, using
      drugs to control the symptoms of colic, continuous abdominal pain and vomiting,
      is effective in the majority of patients. They can therefore be cared for at home
      or in a hospice. A small group of patients, mainly with high obstruction, will
      benefit from a nasogastric tube or venting gastrostomy and fluids can be given,
      if needed, by intravenous or subcutaneous infusion.

PMID- 7521608
TI  - Dyspnoea in advanced malignancies: a palliative care approach.
AB  - The incidence of dyspnoea in advanced malignancies varies from 48-78.6% in
      different studies. A systematic approach enables the clinician to separate non
      malignant causes from those due to complications of malignancy. Specific
      treatment should be considered for airway obstruction, secondary chest infection,
      pleural effusions and superior vena cava obstruction. Morphine remains the most
      effective drug and may be delivered either orally or by inhalation. Nebulised
      anaesthetics are alternatives, while the value of other drugs is uncertain.
      Oxygen therapy and treatment of anxiety are important components.

PMID- 7521609
TI  - Emergencies in palliative care.
AB  - Five groups of events are here considered as emergencies in palliative care:
      haemorrhage, convulsions, fractures, spinal cord compression and acute confusion.
      Incidence, causes and management of these form the major part of this article.
      Emergencies in palliative care also include sudden severe exacerbation of
      symptoms. Therefore, onset of severe pain, exacerbation of breathlessness, and
      worsening of other symptoms are also discussed with their appropriate treatment.
      A small armamentarium of appropriate medications is thus shown to cover treatment
      of the various emergencies that may arise. As palliative care deals with patients
      who are suffering from progressive fatal conditions, death is the expected end.
      Nevertheless, however well the family are prepared, death often appears for them
      as an emergency. Comment is made regarding this family emergency in the care of
      terminally ill people. Attention in this article is focussed on medical
      treatment. In the care of the emergency event, however, and in all palliative
      care, management includes making the patient comfortable, thinking of the needs
      of other patients and relatives observing the event, explaining what is happening
      and is being done, involving other members of the team, and communicating
      reassurance to the patient and the relatives as well as to other observers.

PMID- 7521610
TI  - Palliative care in bilateral malignant ureteric obstruction.
AB  - Bilateral ureteric obstruction is an uncommon complication arising from
      malignancy and its treatment. There are several effective methods of overcoming
      the obstruction but the choice of option requires careful consideration of
      various factors pertaining to each individual. These factors include the
      patient's age, premorbid health and lifestyle, and the extent and rate of
      disease. Patient and family expectations, goals and priorities need careful
      consideration in the context of the patient's prognosis. If measures to relieve
      the obstruction are not to be undertaken, symptom control then becomes paramount.
      This paper explores the various options and decision making by focusing on
      representative patients encountered in the practice of the Central Sydney Area
      Health Palliative Care Service.

PMID- 7521611
TI  - Half body irradiation for palliation of widespread metastatic bone disease.
AB  - An analysis is made of 134 patients treated by a single dose half body
      irradiation at the Department of Therapeutic Radiology, Singapore General
      Hospital. A total of 149 fields were treated with 15 patients receiving both
      upper and lower half treatments. This technique achieved a more than 70%
      subjective pain relief in the patients who had widespread bony metastases. Side
      effects were minimal and this technique has been used on an outpatient basis
      since the first preliminary study in 1986. There was a dose response, more than
      75% (75 out of 97 patients) with pain relief using doses of 700 cGy and above.
      Sensitive tumours also produced better results with nasopharyngeal carcinoma,
      prostate and breast having pain relief in more than 70% of patients. The largest
      group of patients (51 cases) treated was nasopharyngeal carcinoma, as this tumour
      is fairly common locally and often presents with bony metastases as the first
      site of spread.

PMID- 7521612
TI  - Administration of drugs by infusion pumps in palliative medicine.
AB  - A retrospective study was carried out in 100 adult patients with advanced
      malignant disease. They were given subcutaneous continuous infusions of
      medication for symptom relief. The drugs were administered through a butterfly
      needle inserted subcutaneously in the anterior chest wall using a battery
      operated infusion pump. The indications for using this technique were inability
      to swallow due to deteriorating general condition, oesophageal obstruction,
      intestinal obstruction, severe nausea and vomiting, terminal dyspnoea and poor
      pain control with oral opiates. All patients received morphine; other drugs
      administered through the syringe driver included hyoscine, metoclopramide,
      cyclizine, dexamethasone and midazolam. Ninety-four patients continued
      subcutaneous infusion until death. The mean duration of treatment was 9.1 days.
      The treatment was well tolerated by the patients and controlled their symptoms
      satisfactorily in the great majority. The use of continuous subcutaneous infusion
      via a syringe driver gives good symptom control. In the last days of life when
      the patients have difficulty tolerating oral medication, continuous subcutaneous
      infusion is a superior alternative to frequent intermittent parenteral
      injections.

PMID- 7521613
TI  - The palliative effects of octreotide in malignant disease.
AB  - Octreotide is a synthetic analogue of somatostatin with a longer half-life than
      the native peptide. It has been used extensively in a variety of clinical
      settings for some years. More recently, its uses in malignant disease processes
      have been studied and it is proving to be an excellent addition to the palliative
      care pharmacy. We look at the current uses of octreotide for the palliation of
      malignant disease with particular emphasis on inoperable malignant bowel
      obstruction. Octreotide may palliate nausea and vomiting in this distressing
      condition when other therapies fail. Octreotide may also control severe diarrhoea
      and help in the closure of fistulae from benign and malignant conditions. It has
      unique analgesic properties. Radio-labelled isotopes of octreotide may be used to
      image some tumours. Recently, it has also shown potential in anti-cancer
      treatment.

PMID- 7521614
TI  - Intracavitary radiotherapy for nasopharyngeal carcinoma--palliation or cure?
AB  - Although nasopharyngeal carcinoma is classically treated by external irradiation,
      the technique invariably results in decreased parotid secretions and rapid tooth
      decay. For the treatment of locally relapsed tumours, nasopharyngectomy, though
      effective, may not always be available for routine salvage, especially in endemic
      areas. A pilot study was made of ten patients having limited local relapses who
      were treated by intracavitary irradiation (ICI) with or without an abbreviated
      dose of external irradiation. With ICI alone, relapses outside the nasopharynx
      occurred in two patients but the combination with even an abbreviated dose of
      external irradiation was more successful. Nevertheless, even with relapse,
      patients were free from local symptoms for a median time of over two years--an
      excellent palliation result. More work, preferably at the multi-centre level,
      should be done to define more precisely the role of intracavitary irradiation for
      nasopharyngeal carcinoma.

PMID- 7521615
TI  - Intraluminal brachytherapy in the treatment of oesophageal cancers--some
      preliminary results.
AB  - Cancer of the oesophagus is the sixth commonest cancer in males in Singapore. The
      majority occur in the elderly and patients are often debilitated at presentation.
      Treatment is often aimed at palliation only. In this article, the preliminary
      results of 15 patients treated solely on a high dose rate remote afterloading
      Gammamed brachytherapy machine with an Iridium 192 (Ir192) source are reported.
      The patients were given 15 Gray (Gy) in a single or two 7.5 Gray fractions. All
      the patients treated had some improvement of their dysphagia, and seven out of 11
      (63%) evaluable patients had symptom improvement lasting at least 11 weeks.

PMID- 7521616
TI  - Use of high dose rate gammamed brachytherapy in the palliative treatment of
      gynaecological cancer.
AB  - From January 1992 to December 1993, 24 patients with advanced and incurable
      malignancies of the female genital tract were treated at the Department of
      Therapeutic Radiology, Singapore General Hospital, with high dose rate (HDR)
      brachytherapy. Results from the evaluation of these patients showed an overall
      complete palliation of symptoms in 16 of 23 (69.5%) patients. Total cessation of
      bleeding was observed in 14 of 20 (70%) and pain relief in two of three (66.6%).
      Of the 16 patients who exhibited full symptomatic response, almost half (43.7%)
      had clinical complete resolution of their local disease at last follow-up. Acute
      complications following treatment were minimal and only in one was intervention
      required to stop radiation haemorrhagic cystitis. We conclude that the use of HDR
      brachytherapy either alone or in combination with external beam radiotherapy can
      provide effective palliation for malignant tumours involving the female genital
      tract with minimal acute toxicity.

PMID- 7521617
TI  - Palliative care in acquired immunodeficiency syndrome (AIDS): problems and
      practicalities.
AB  - The World Health Organisation estimates that over 1.5 million human
      immunodeficiency virus (HIV) infections have occurred to date in South and South
      East Asia. As most of these patients will develop acquired immunodeficiency
      syndrome (AIDS) in the coming decade, health services in the region face a major
      challenge in meeting their needs. While treatments are available which prolong
      the lives of patients with AIDS, most will eventually die of their disease, and
      attention needs to be given to controlling pain and other symptoms and improving
      quality of life. Providing palliative care for patients with AIDS raises complex
      issues not normally encountered in traditional palliative care practice. Based on
      the author's experience with the Central Sydney Area Palliative Care Service in
      Sydney, Australia, this paper discusses the problems and practicalities involved
      in palliative care for adult patients with advanced AIDS, such as clinical
      decision making, pain and other symptom control, psychosocial issues and terminal
      care. Representative case histories are described to illustrate how the
      palliative care physician can start to approach some of the dilemmas created by
      this demanding yet growing area of palliative care.

PMID- 7521618
TI  - Physician/nursing roles and perspectives in relationship to delivery of
      palliative care.
AB  - Palliative or hospice care developed as a new discipline because the needs of the
      dying patient and family were not adequately met by the established health care
      system. The focus on the technological aspects of medicine for diagnosis and
      treatment has resulted in the neglect of the social, emotional and spiritual
      problems experienced by patients suffering from a terminal disease. Care of the
      dying is an active process that requires frequent assessments and the aggressive
      pursuit of appropriate therapies to control both physical and emotional symptoms.
      Models of practice used by medicine and nursing are compared and related to the
      delivery of effective and compassionate care to the dying.

PMID- 7521619
TI  - Role of the social worker in palliative care.
AB  - The role of the social worker in the palliative care team is defined by five main
      functions--assessment, counselling, liaison with local resources and agencies,
      training and development activities, and staff support. The difference between
      the social work task, which may be undertaken by any member of the palliative
      care team, and the social work role is emphasized. Social workers bring to the
      team particular skills in working with families, children and groups. Their
      training helps them to locate the patient and family within a social and cultural
      context and thus to exploit resources which may help the family to resolve the
      difficulties they face. A method of family assessment is explored and a case
      study illustrates a family intervention including direct work with children.

PMID- 7521620
TI  - Central Sydney Palliative Care Service: potential and limitations of an
      integrated palliative care service based in a metropolitan teaching hospital.
AB  - Palliative care needs to be available wherever needed, in hospital and home, and
      should be part of mainstream health care. Palliative care should be concurrent
      with anti-disease therapy, and includes but goes beyond "terminal care". The
      World Health Organization (WHO) encourages such development. Palliative care in
      Australia takes on many forms. Central Sydney Palliative Care Service based in
      Royal Prince Alfred Hospital (RPAH), Camperdown, is an example of mainstream
      palliative care integrating home and hospital care. Almost all units of RPAH
      refer patients to the palliative care service. Approximately 1000 new patients
      are referred annually by doctors (specialists or general practitioners) for
      medical consultation. Registrar (fellow) training in palliative medicine is a
      feature of the service. Palliative care in a hospital or community-based service
      is an issue of justice and equity, and gives structure to compassion.

PMID- 7521621
TI  - Development of cancer pain relief and palliative care in the Philippines.
AB  - The article describes the development and progress of cancer pain relief and
      palliative care in the Philippines from 1986 onwards. The strategy employed was a
      stepwise progression that began with the establishment of government policy,
      followed by measures to improve availability and accessibility to oral morphine,
      and finally, continuing nationwide professional education. Key elements to
      successful implementation were the presence of a national cancer control
      programme; the active participation of the World Health Organization, the
      Department of Health, the Philippine College of Surgeons, and the Philippine
      Cancer Society Inc; and research development and utilisation. Data from three
      clinical studies are also presented, which showed the efficacy of the WHO Method
      of Cancer Pain Relief among samples of Philippine patients, and that cancer pain
      relief alone did not significantly improve overall quality of life, demonstrating
      the need for comprehensive palliative care.

PMID- 7521622
TI  - Recent progress in cancer pain management and palliative care in Japan.
AB  - One out of every four deaths in Japan is due to cancer, so that health-care
      workers and the lay public have gradually become aware of the importance of
      cancer pain relief and palliative care in recent years. In 1984, the feasibility
      and effectiveness of the WHO method for relief of cancer pain was demonstrated in
      Japanese cancer patients. Thereafter, information on the latest knowledge and
      skills in cancer pain relief and palliative care has been disseminated through
      medical meetings, publications and mass communication networks. The national
      government published manuals of care for terminally ill cancer patients and
      amended narcotics regulation in order to improve the accessibility of opioid
      analgesics, especially morphine, to cancer patients with pain. These activities
      resulted in a 35-fold increase in the annual consumption of morphine preparations
      for medical purposes between 1979 and 1992. However, the annual consumption per
      capita is still much smaller than that in other developed countries, indicating
      the need for further information dissemination and professional education in the
      implementation of palliative care programmes.

PMID- 7521623
TI  - Euthanasia--definition, dangers and alternatives.
AB  - There is as yet (1992) no law specifically allowing euthanasia, the active
      intervention to end a patient's life. The discussion has so far been restricted
      to such action as taking place at a patient's request, but evidence from the
      Netherlands appears to show that the move to involuntary euthanasia is a real
      danger. Palliative medicine offers appropriate treatment for relief and support
      where limits are set on interventions that would no longer be in a patient's best
      interests. It is possible to relieve distress by using the increasing knowledge
      in this field. It is important to distinguish this from euthanasia and the term
      "passive euthanasia" is confusing and unfortunate. Those with extensive
      experience in the treatment of advanced cancer have much to share with
      practitioners in other specialties, not least in the possible achievements of
      both patient and family at the end of life. Society has the responsibility for
      including them in its concern to the end of life and for supporting those who
      find it difficult to believe in any meaning in their existence.

PMID- 7521624
TI  - Enteropathogenic and enteroadherent-aggregative Escherichia coli in children with
      persistent diarrhoea and malnutrition.
AB  - Our investigation of 61 children with persistent diarrhoea and malnutrition (PDM)
      aimed to characterize in them the range of enteropathogenic E. coli. Age- and sex
      matched control groups consisted of 42 healthy children and 16 children with
      marasmus but without diarrhoea. E. coli isolates from stool cultures were
      serotyped, examined for Vero cells cytotoxicity, tested for enterotoxin
      production (LT, ST, VTI, and VTII). Synthetic oligonucleotide probes were used to
      test for enteroinvasivity, EPEC adherence factor, and for EAggEC. Classical E.
      coli serotypes commonly associated with diarrhoea (O18, O26, O119, O126) were
      isolated from six of 60 (10%) children with PDM. Serotype O126 was isolated from
      two of 42 (4.8%) healthy children and serotype O119 from one of 16 (6%) marasmic
      controls. Testing for Vero toxin production was negative in all isolates.
      Classical ETEC were confirmed in four of 60 (ST 2; LT 2) cases of PDM; no ETEC
      were recovered from 58 control patients. EAggEC were identified in five children
      with PDM and in five healthy controls without diarrhoea or malnutrition. This
      controlled study has shown that, in The Gambia, E. coli carrying known virulence
      factors are prevalent but, with the exception of enterotoxigenic E. coli, the
      various forms of pathogenic E. coli do not seem to be important pathogens in
      children with persistent diarrhoea.

PMID- 7521625
TI  - Aetiology of chronic diarrhoea in children: experience at King Khalid University
      Hospital, Riyadh, Saudi Arabia.
AB  - Forty-eight cases of chronic diarrhoea in children seen at King Khalid University
      Hospital over a 5-year period were analysed. The mean age at presentation was 1.8
      years (range 0.08-10 years); 34 were boys and 14 girls. Forty-four patients were
      Saudi and four were non-Saudi Arabs. Most children presented with failure to
      thrive and pallor. The aetiological factors identified were: the post-gastro
      enteritis syndrome with or without lactose intolerance in 16 (33%); coeliac
      disease in ten (21%); congenital chloride diarrhoea in five (10%); glucose
      galactose malabsorption and acrodermatitis enteropathica, each in three (6%);
      ulcerative colitis, intestinal lymphangiectasia, cow's milk protein intolerance
      and ataxia telangiectasia, each in two (4%); and giardiasis, immune deficiency
      and cystic fibrosis, each in one (2%). Five children died.

PMID- 7521626
TI  - Improved outcome of systemic lupus erythematosus among children in Durban, South
      Africa.
AB  - As systemic lupus erythematosus (SLE) is an uncommon disorder of childhood and is
      rarely seen among children in developing countries, management is not based on
      secure criteria and is often a matter of individual preference. In our previous
      experience, all four children suffering from SLE died soon after diagnosis.
      Aggressive therapy has been recommended to deal with such problems in the third
      world. We now report improved management of four more children with SLE seen
      since 1988 at King Edward VIII Hospital and observed for from 21 to 57 months.
      All our patients had evidence of renal involvement, with severe disease in two
      patients confirmed on renal biopsy; three had neurological involvement. The
      mainstay of treatment was a combination of steroids, azathioprine and chloroquine
      together with pulse methylprednisolone or cyclophosphamide for severe relapses.
      Disease activity was closely monitored, using clinical and laboratory criteria.
      Following therapy, all patients are in a stable condition and in clinical
      remission; one has mild renal impairment. These early results suggest that the
      judicious use of a few drugs, together with regular and meticulous follow-up, can
      greatly improve the prognosis of childhood SLE, even in third world countries.

PMID- 7521627
TI  - Respiratory syncytial virus infections in malnourished children.
AB  - The prevalence of respiratory syncytial virus (RSV) infection among severely
      malnourished children was studied at the University of Benin Teaching Hospital,
      Benin City, Nigeria at a time when the infection was known to be prevalent in the
      community. Nasopharyngeal washings were obtained from subjects on admission and
      thereafter every 4 days until discharge. RSV was detected by ELISA technique. Of
      20 well nourished children who served as controls, 11 were ELISA-positive for RSV
      (55%). Eight (16%) of the 51 patients who were malnourished were ELISA-positive,
      four of whom (8%) had nosocomial infection. Fever and rhinitis were the most
      common presenting features in the RSV-infected malnourished children. None of the
      children showed any clinical or radiological signs of lower respiratory tract
      infection. Malnourished children appear not to be at increased risk of RSV
      infection, and those who contract the infection usually do not manifest severe
      disease.

PMID- 7521629
TI  - Chronic illness in preschool Jordanian children.
AB  - This is a prevalence study of chronic illness and disability in Jordanian
      children 0-7 years of age living in Sweileh, a suburb of Amman. The study was
      performed in 1991. A total number of 2528 children were examined, representing
      more than 95% of the children 0-7 years in the catchment area. Of these, 198
      (7.8%) had a disability or a chronic disease. Fifty-eight children (2.6%) were
      classified as moderately or severely affected. Boys were in the majority.
      Compared with the findings in European and American studies, congenital eye
      diseases and severe mental retardation were common while atopic diseases were
      rare. Consanguinity seemed to be important in the aetiology of chronic diseases.
      Social background factors did not have a substantial impact on the overall
      prevalence, but psychomotor delay and a sequel to an injury were more common in
      children from poor families.

PMID- 7521631
TI  - Ocular abnormalities in children from a Malaysian school for the deaf.
AB  - The prevalence of ocular abnormalities was studied in 165 children from a
      Malaysian school for the deaf. Ninety-five children (57.6%) had one or more
      ocular abnormalities. Rubella retinopathy was the commonest form of ocular
      abnormality (35.2%). Refractive errors were found in 23 children (13.9%).
      Refractive errors in the rubella group were significantly more common than in the
      non-rubella group of deaf children (p < 0.001) (chi 2 test). Thirteen children
      had congenital anomalies causing significantly impaired vision. Ophthalmological
      examination of deaf children helps in the detection of cases with rubella eye
      signs and thus helps to identify the cause of deafness. Since deaf children are
      at greater risk of visual and ocular abnormalities, periodical ophthalmological
      examination should be carried out in these children.

PMID- 7521628
TI  - Stroke in children: a study of 21 cases from Saudi Arabia.
AB  - Twenty-one cases of stroke were observed in children aged between 4 months and 15
      years attending two large hospitals in Saudi Arabia over a 10-year period. The
      number constitutes two per cent of all cases of stroke managed in these hospitals
      during that period. Eleven cases were associated with cerebral arterial
      infarction, nine with cerebral haemorrhage and one with venous infarction. The
      main aetiological factors were attributable to embolism of cardiac origin,
      infections, coagulation disorders, haemoglobinopathies and arteriovenous
      malformations. Although stroke in children is regarded as rare, its relative
      frequency in Saudi society is probably higher than in western societies.

PMID- 7521632
TI  - Severe derangement of the coagulation profile following multiple bee stings in a
      2-year-old boy.
AB  - Occasionally, insect bites producing systemic complications are the reason for
      admission to paediatric intensive care. We report an interesting case of multiple
      bee stings in a 2-year-old boy. The boy, who was stung more than 200 times by
      honey bees, had a severely deranged coagulation profile with marked elevation of
      the hepatic enzymes. This complication has not been reported to date. Prompt
      intensive supportive care led to the child's total recovery.

PMID- 7521630
TI  - Streptococcal toxic shock-like syndrome: case report and review of the
      literature.
AB  - Streptococcal toxic shock-like syndrome is a newly recognized complication of
      infections by group A beta-haemolytic streptococci (GABHS). Previous reports of
      this syndrome have originated from developed countries, predominantly North
      American and Europe. This report describes a 5-year-old Saudi child who developed
      this syndrome in association with streptococcal pharyngitis. It indicates that
      the recent resurgence of severe GABHS diseases is a global phenomenon.

PMID- 7521633
TI  - Serum vitamin A levels of preschool children in a Nigerian rural community.
AB  - A study was carried out to determine the serum vitamin A levels of 250 preschool
      children in a rural community in eastern Nigeria. The children were aged between
      2 months and 5 years and comprised 117 boys and 133 girls. A total of 23 (9.2%)
      children had 'deficient levels' (< 10 micrograms/dl) and 41 (16.4%) had 'low
      levels' (< 20 micrograms/dl) according to the Interdepartmental Committee on
      Nutrition for National Defence criteria for the interpretation of serum vitamin A
      levels. The sex distribution showed that 14 (11.97%) boys and nine (6.77%) girls
      had deficiency levels. A history of night blindness was obtained in six (3.7%) of
      162 children aged 3-5 years.

PMID- 7521634
TI  - Prevalence of hepatitis B in !Kung (San) children from Bushmanland, Namibia.
AB  - Serum samples from 248 predominantly !Kung children (aged 5-19 years) attending
      various bush schools and a clinic in Bushmanland, northern Namibia were examined
      for the presence of hepatitis B virus (HBV) markers by radioimmunoassay. HBsAg
      was detected in 18 (7.3%) children while 117 (47.6%) showed one or more markers
      of HBV infection. These prevalence rates are lower than those of the closely
      situated territory of Kavango to the north and East Caprivi to the north-east. No
      significant difference in HBs antigenaemia between !Kung boys and girls was found
      (p > 0.05). However, HBs antigenaemia was found to vary between children in
      different bush schools. A significantly higher number of children attending the
      Omatako bush school were positive for HBsAg than the number attending the Luhebu
      bush school (p < 0.0167). These local variations could assist in the initial
      targeting of HBV vaccine to high-risk areas. In situ investigations of
      hyperendemic foci in Bushmanland, Namibia should help to elucidate the variation
      in HBs antigenaemia and the factors responsible for transmission of HBV.

PMID- 7521635
TI  - The management of fungal obstructive uropathy in neonates and infants.
AB  - Obstructive uropathy caused by upper urinary tract fungal ball formation is an
      uncommon but well recognized clinical entity. The clinical course and management
      of an infant with unilateral fungal ball obstruction is described. Ultrasound and
      Tc-diaminotetraethylpentacetic acid (DTPA) renal scan contributed significantly
      to the diagnosis and management of this patient. Complete resolution of the
      obstruction was achieved by treatment with intravenous amphotericin B and oral 5
      fluorocytosine. The clinical course and management of 35 patients described in
      the literature indicate that prematurity, use of broad spectrum antibiotics,
      prolonged hospital stay and the use of intravascular catheters are predisposing
      factors. The mortality rate is 34%. Young age, small size, the presence of
      candidaemia and withholding antifungal therapy are poor prognostic factors. A
      rational plan of treatment, extrapolated from the literature, is presented which
      may help to reduce the mortality rate in this condition.

PMID- 7521636
TI  - A randomized controlled trial of two acellular pertussis-diphtheria-tetanus
      vaccines in primary immunization in Ghana: antibody responses and adverse
      reactions.
AB  - Two acellular pertussis vaccines combined with diphtheria and tetanus toxoids
      (APDT vaccines) were compared with a whole cell PDT (WCPDT) vaccine in primary
      immunization in Ghana. One is a liquid vaccine which is used for general
      immunization in Japan and the other is a freeze-dried vaccine newly developed as
      a heat-stable vaccine. Eighty-nine infants were recruited in the study. Sixty
      eight who completed three doses of the immunization were assessed for
      immunological responses. Twenty-one dropped out because of sickness or moving
      from the study area. A total of 242 vaccinations in 89 infants were followed up
      for adverse reactions. Geometric mean titres (GMTs) to filamentous haemagglutinin
      in the two APDT vaccinees were significantly higher than in the WCPDT recipients.
      GMTs to pertussis toxin, diphtheria and tetanus toxoids were not significantly
      different among the three groups. Seropositive rates to pertussis antigens,
      tetanus and diphtheria toxoids were 94.4 to 100% in the two APDT vaccines.
      Systemic reactions within 7 days of inoculation were similarly low in the three
      groups, but significantly fewer infants had local reactions after either of the
      two APDT vaccines than after the WCPDT vaccine.

PMID- 7521637
TI  - Epidemiology of invasive Haemophilus influenzae infections in Cape Town, South
      Africa.
AB  - The full spectrum of invasive Haemophilus influenzae disease has not been
      documented previously in Africa. This 1-year prospective study was designed to
      determine the epidemiology of invasive Haemophilus influenzae disease in Cape
      Town children. During this period, 142 children with invasive disease were
      hospitalized; 85 (59.9%) presented with meningitis, 35 (24.6%) with pneumonia and
      22 (15.5%) with other diseases. No cases of epiglottitis were seen. Sixty per
      cent of cases were male and 40% female. The median age of the children was 9
      months, with a range of 1-144 months, and 65.5% were aged < 12 months.
      Neurological dysfunction was noted in 40% and 18% of children with meningitis on
      admission and discharge, respectively. The overall case fatality rate (95%
      confidence intervals) was 9.2% (4.9-15.7), and for meningitis, pneumonia and
      septicaemia it was 4.7% (1.2-16.4), 14.3% (4.6-31.8) and 40% (8-78.1),
      respectively. Serotype b accounted for 86.5% of all cases, 97.3% of cases of
      meningitis, 71.4% of cases of pneumonia, 50% of cases of septicaemia, all cases
      of arthritis and cellulitis and none of mastoiditis. The incidence rates (95%
      confidence intervals) for all invasive type b infections were 169 (122-198) and
      47 (39-57) per 100,000 population for children < 1 and < 5 years, respectively.
      For meningitis the rates were 112 (84-148) and 34 (25-40) per 100,000,
      respectively. Rates for mixed race and white children were similar, but those for
      black children were more than double those rates.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7521638
TI  - Primary vs metastatic hepatic carcinoma. An immunohistochemical study of 34
      cases.
AB  - The distinction between primary and metastatic hepatic epithelial malignant
      neoplasms can often be difficult if histologic features alone are used. The
      purpose of this study was to determine whether certain immunohistochemical
      markers could be used to aid in the diagnosis. The cases that were studied
      included 14 hepatocellular carcinomas, 10 cholangiocarcinomas, and seven
      metastatic adenocarcinomas; three cases of poorly differentiated carcinoma (not
      otherwise specified) were also studied. The antibodies that were chosen included
      alpha-fetoprotein, alpha 1-antitrypsin, monoclonal carcinoembryonic antigen, Leu
      M1, B72.3, factor XIIIa, and Le(x). We found that the cases of hepatocellular
      carcinoma displayed cytoplasmic reactivity for alpha 1-antitrypsin, alpha
      fetoprotein, and factor XIIIa. The cases of cholangiocarcinoma showed membranous
      and cytoplasmic reactivity for Le(x) but only cytoplasmic reactivity for Leu-M1
      and B72.3, whereas the opposite pattern of staining was found in cases of
      metastatic adenocarcinoma. We conclude that immunohistochemical studies can be
      useful in the distinction of primary vs metastatic hepatic malignant neoplasms
      and recommend a panel of alpha 1-antitrypsin, alpha-fetoprotein, Leu-M1, B72.3,
      factor XIIIa, and Le(x).

PMID- 7521639
TI  - RNA polymerase: structural determinant of the chromatin loop and the chromosome.
AB  - Current models for RNA synthesis involve an RNA polymerase that tracks along a
      static template. However, research on chromatin loops suggests that the template
      slides past a stationary polymerase; individual polymerases tie the chromatin
      fibre into loops and clusters of polymerases determine the basic structure of the
      interphase and metaphase chromosome. RNA polymerase is then both a player and a
      manager of the chromosome loop.

PMID- 7521640
TI  - Mutation frequency decline revisited.
AB  - 'Mutation frequency decline' (MFD) was discovered about forty years ago, and
      described as the disappearance of a particular class of ultraviolet light-induced
      mutations in Escherichia coli that occurred whenever protein synthesis was
      briefly inhibited immediately after irradiation. Later, MFD was interpreted as an
      excision repair anomaly uniquely affecting nonsense suppressor mutations induced
      in certain tRNA genes. Never fully understood, MFD has recently been linked to
      the newly discovered transcription-coupled rapid repair of ultraviolet damage on
      the template strand of active genes. This article recalls the emergence and
      development of the MFD story, and offers a new way to explain it and its relation
      to strand-specific excision repair.

PMID- 7521641
TI  - Phosphotyrosine inhibition and control of vascular endothelial cell proliferation
      by genistein.
AB  - Genistein (4',5,7-trihydroxyisoflavone) is a potent anti-angiogenic compound. We
      investigated the inhibition of phosphotyrosine as a putative signaling mechanism
      utilized by the drug in modulating basic fibroblast growth factor (bFGF)-mediated
      vascular endothelial cell proliferation. The studies included the effect of
      genistein on DNA synthesis, cell viability, phosphotyrosine induction and
      characterization of the FGF receptor (FGFR). DNA synthesis was attenuated
      significantly by genistein in a concentration- and time course-dependent manner
      with relatively low cytotoxicity during a 16-24 hr exposure (IC50 = 12.5 microM;
      LC50 = 300 microM). Ligand-stimulated cells exhibited significant increases in
      phosphotyrosine, affecting FGFR and several tyrosine kinase substrates, ranging
      in size from M(r) 28 to 200 kDa. Inhibition of phosphotyrosine induction as shown
      by western blots occurred only at high concentrations of the drug (> 500 microM).
      These results were supported by results obtained using fluorescence
      immunocytochemistry. FGFR was shown to be FGF-R1 beta 2, a dimer of approximately
      85 and 62 kDa, which was prevented from being autophosphorylated when relatively
      high concentrations of the drug were applied. Low dose (< 20 microM) inhibition
      of DNA synthesis by genistein did not correlate with the high concentration
      required for phosphotyrosine inhibition. The data suggest that although cell
      stimulation results in phosphotyrosine induction, inhibition of phosphotyrosine
      is not required for inhibition of DNA synthesis. Furthermore, in endothelial
      cells, inhibition of DNA synthesis by genistein is not mediated primarily by the
      inhibition of protein tyrosine kinase activity.

PMID- 7521642
TI  - Synergistic interactions between selective pharmacological inhibitors of
      phosphodiesterase isozyme families PDE III and PDE IV to attenuate proliferation
      of rat vascular smooth muscle cells.
AB  - The interaction between selective inhibitors of 3',5'-cyclic-nucleotide
      phosphodiesterase (PDE) III (cyclic GMP inhibited phosphodiesterase) and
      selective inhibitors of PDE IV (Ro 20-1724 inhibited phosphodiesterase) to
      attenuate fetal bovine serum-stimulated incorporation of [3H]thymidine into DNA
      and cell proliferation was studied in a line (A10) of vascular smooth muscle
      cells (VSMC). The nonselective PDE inhibitors 3-isobutyl-1-methylxanthine (IBMX)
      and papaverine attenuated DNA synthesis with EC50 values (16 and 18 microM,
      respectively) in the same range as their published IC50 values (2-50 and 2-25
      microM, respectively) as PDE inhibitors. The selective PDE III inhibitors CI-930
      and cilostamide used alone attenuated DNA synthesis with EC50 values (> 300 and
      5.3 microM, respectively) that were much higher than published IC50 values (0.15
      0.46 and 0.005-0.064 microM, respectively) for inhibition of PDE III. In the
      presence of the PDE IV inhibitor rolipram (10 microM), their EC50 values were
      shifted (0.66 and 0.16 microM, respectively) much closer to their respective IC50
      values. When the selective PDE IV inhibitors rolipram and Ro 20-1724 were used
      alone, they attenuated DNA synthesis with EC50 values (111 and > 100 microM,
      respectively) much higher than their IC50 values (0.6-2.6 and 2-13 microM,
      respectively) as inhibitors of PDE IV, but 10 microM CI-930 (PDE III inhibitor)
      shifted their EC50 values (0.56 and 1.5 microM, respectively) much closer to
      their IC50 values. In experiments that assessed VSMC proliferation using the MTT
      [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] method, IBMX and
      papaverine attenuated proliferation with EC50 values (27 and 58 microM,
      respectively) close to their IC50 values. CI-930 and cilostamide used alone did
      not cause 50% attenuation of proliferation at the highest concentrations tested
      (100 and 10 microM, respectively). In the presence of 5 microM rolipram, however,
      their effects were enhanced greatly with EC50 values (0.86 and 0.23 microM,
      respectively) that were close to their IC50 values as PDE III inhibitors.
      Similarly, rolipram and Ro 20-1724 attenuated VSMC proliferation with EC50 values
      close to their IC50 values in the presence (2.1 and 4.6 microM, respectively) but
      not in the absence (> 100 and > 10 microM, respectively) of 2 microM CI-930. The
      interactions between PDE III inhibitors and PDE IV inhibitors to attenuate DNA
      synthesis and VSMC proliferation were synergistic as determined by the
      combination index. The data demonstrate that the synergistic interactions that
      attenuate incorporation of [3H]thymidine into DNA are accompanied by synergistic
      attenuations of VSMC division.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7521643
TI  - The study of HCV antibody and serologic tests for syphilis in Thai patients with
      gynecologic disorders.
AB  - Investigation for prevalence of antibodies to hepatitis C virus (HCV) and to
      Treponema pallidum was conducted in 883 females with gynecologic disorders who
      were admitted to the gynecological ward of the Department of Obstetrics and
      Gynecology, Siriraj Hospital during April to August 1991. The study population
      consisted of 678 patients with malignancies and 205 patients with benign
      diseases. Anti-HCV antibody was found in 3.1% of the cases with malignancies and
      1.46% of those with benign diseases. Among the gynecologic malignant group, the
      patients with carcinoma of cervix had the highest prevalence of HCV antibody
      (3.6%). The positive serologic tests for syphilis in patients with carcinoma of
      cervix (9.8%) were significantly higher from those in patients with ovarian
      carcinoma (3.75%) (p < 0.01). There were 3 cases with carcinoma of cervix who
      were simultaneously sero-positive for both HCV and syphilis.

PMID- 7521644
TI  - Application of indirect immunofluorescence microscopy to colony identification of
      Pseudomonas pseudomallei.
AB  - Indirect immunofluorescence microscopy was used as a colony identification method
      of Pseudomonas pseudomallei isolates. The antisera against lipopolysaccharide and
      protein fractions of P. pseudomallei were prepared in guinea pigs and rabbits.
      With these antisera and fluorescence-labelled anti-guinea pig IgG and anti-rabbit
      IgG prepared in sheep (goat), indirect immunofluorescence microscopy was
      conducted on the colonies of P. pseudomallei and other species of bacteria. The
      overall results indicated that this method is efficient, rapid and specific for
      identification of P. pseudomallei colonies from clinical specimens.

PMID- 7521645
TI  - The effects of copollutants on the metabolism and DNA binding of carcinogens.
AB  - Copollutants found in air samples and other complex chemical mixtures may alter
      the metabolism, and thus the biological activity, of chemical carcinogens. As an
      initial step to determine whether the metabolism and DNA binding of carcinogenic
      nitrated polycyclic aromatic hydrocarbons found in diesel exhaust particles are
      altered by copollutants, we studied the effect of pyrene on the metabolism and
      DNA binding of 1-nitropyrene, and the effect of pyrene and 1-nitropyrene on the
      metabolism and DNA adduct formation of 1,6-dinitropyrene in male B6C3F1 mice. In
      in vitro incubations using liver microsomes from untreated mice, pyrene was a
      mixed-type inhibitor, with a 6.42-microM appKi. 2-Aminofluorene and 3-amino-2
      methoxydibenzofuran were also effective inhibitors of 1-nitropyrene metabolism.
      Pyrene did not affect the total in vivo excretion of 1-nitropyrene when
      coadministered to mice at either a 10-fold or a 250-fold molar excess. At the
      higher dose of pyrene, however, the urinary excretion of 1-nitropyrene
      metabolites decreased by approximately 20%, whereas the concentration of fecal
      metabolites increased by the same amount. Similar in vivo experiments were
      conducted using 2-aminofluorene as the inhibitor. The excretion of 1-nitropyrene
      was not significantly affected by 2-aminofluorene treatment. Treatment-related
      DNA adducts were not detected by 32P-postlabeling analyses of liver DNA when 1
      nitropyrene was administered by itself or with a 20- or 250-fold molar excess of
      pyrene. The coadministration of pyrene or 1-nitropyrene had no effect on the
      total excretion of 1,6-dinitropyrene metabolites. A single major adduct that
      coeluted with N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene was detected in
      hepatic DNA from mice treated with 1,6-dinitropyrene. The concentration of this
      adduct was significantly decreased by the coadministration of a 25-fold molar
      excess of pyrene and was significantly increased by simultaneous treatment with a
      25-fold molar excess of 1-nitropyrene. These results demonstrate the effect of
      copollutants on potentially carcinogenic components of diesel exhaust and urban
      air.

PMID- 7521646
TI  - Guiding the selection of human antibodies from phage display repertoires to a
      single epitope of an antigen.
AB  - We have developed a strategy for guiding the selection of human antibody
      fragments from phage display repertoires to a single epitope of an antigen, using
      rodent monoclonal antibodies as a template. Thus the heavy chain of a rodent
      antibody (MAb32) directed against human tumor necrosis factor alpha (TNF alpha)
      was cloned and paired as a template chain with a repertoire of human light chains
      for display as Fab fragments on filamentous phage. The phage were selected by
      binding to the antigen. The selected human light chains were in turn paired with
      a repertoire of human heavy chains displayed on phage, and the phage selected
      again. The isolated phage displaying human antibody fragments binding to TNF
      alpha also bound to a peptide comprising the N-terminal region of TNF alpha as
      with MAb32. One of the human Fab fragments was recloned for expression as a
      glycosylated human antibody in mammalian cells: Binding to TNF alpha could be
      competed with MAb32 or with anti-serum to the peptide, indicating the same
      epitope. The human antibody was found to have a binding affinity (Kd = 15 nM)
      similar to MAb32 (Kd = 26 nM). The process contrasts with existing means of
      "humanizing" rodent monoclonal antibodies in that the antibodies derived are
      completely human.

PMID- 7521647
TI  - Expansion of hematopoietic progenitor cell populations in stirred suspension
      bioreactors of normal human bone marrow cells.
AB  - We have investigated the potential of stirred suspension cultures to support
      hematopoiesis from starting innocula of normal human bone marrow cells. Initial
      studies showed that the short-term maintenance of both colony-forming cell (CFC)
      numbers and their precursors, detected as long-term culture-initiating cells (LTC
      IC), could be achieved as well in stirred suspension cultures as in static
      cultures. Neither of these progenitor cell populations was affected in either
      type of culture when porous microcarriers were added to provide an increased
      surface for adherent cell attachment. Supplementation of the medium with 10 ng/ml
      of Steel factor (SF) and 2 ng/ml of interleukin-3 (IL-3) resulted in a
      significant expansion of LTC-IC, CFC and total cell numbers in stirred cultures.
      Both the duration and ultimate magnitude of these expansions were correlated with
      the initial cell density and after 4 weeks the number of LTC-IC and CFC present
      in stirred cultures initiated with the highest starting cell concentration tested
      reflected average increases of 7- and 22-fold, respectively, above input values.
      Stirred suspension cultures offer the combined advantages of homogeneity and lack
      of dependence on the formation and maintenance of an adherent cell layer. Our
      results suggest their applicability to the development of scaled-up bioreactor
      systems for clinical procedures requiring the production of primitive
      hematopoietic cell populations. In addition, stirred suspension cultures may
      offer a new tool for the analysis of hematopoietic regulatory mechanisms.

PMID- 7521648
TI  - A new process for the production of clinical dextran by mixed-culture
      fermentation of Lipomyces starkeyi and Leuconostoc mesenteroides.
AB  - A mixed-culture fermentation system was designed for the production of size
      limited dextrans. This process was simpler and more economical than traditional
      methods. It required the establishment of microbial consortia of Lipomyces
      starkeyi ATCC 74054 and Leuconostoc mesenteroides ATCC 10830. Controlling initial
      conditions, growth, and enzyme production by both organisms controlled the
      product size. In this process, both strains were grown separately and then mixed.
      Dextran fermentation was then allowed to proceed. At the desired time (and
      molecular size), the fermentation was harvested. The optimum pH and temperature
      for production of clinical dextran (75,000 MW) were 5.2 (+/- 0.1) and 28 (+/-
      0.5) degrees C, respectively. Varying the ratio of L. mesenteroides to L.
      starkeyi in the inoculum did not significantly affect either the final cell
      ratios or dextran production.

PMID- 7521649
TI  - Redistribution of nuclear antigens linked to cell proliferation and RNA
      processing in mouse oocytes and early embryos.
AB  - We have systematically analyzed by indirect immunofluorescence the subcellular
      distribution of nuclear antigens in relation to developmental stages of maturing
      mouse oocytes and developing embryos. Antigens were of two types: (1) a protein
      whose nuclear localization in interphase somatic cells depends on their
      proliferative state protein recognized by a monoclonal antibody 43B1N, and (2)
      snRNP polypeptides recognized by autoimmune sera of anti-Sm and anti-RNP type.
      The protein recognized by 43B1N was present in the germinal vesicle of oocytes
      from antral follicles, but absent from the nuclei during the first hours of
      embryonic life up to the middle to late 2-cell stage. Starting from this stage,
      it was always found in nuclei of interphase blastomeres, where its "speckles" co
      localized with the speckles containing high concentrations of snRNP polypeptides.
      SnRNP polypeptides recognized by anti-Sm and anti-RNP sera were in turn found in
      nuclei of all developmental stages. When embryos were treated with aphidicolin or
      cytochalasin D to arrest cell division, the 43B1N reacting protein was again
      localized in the pronuclei at 42 hr post-hCG, i.e., slightly later than the onset
      of transcriptional activity. These results suggest a progressive building up of
      nuclei during embryonic development, which could influence gene expression.

PMID- 7521650
TI  - Mouse preimplantation embryo development in vitro: effect of sodium concentration
      in culture media on RNA synthesis and accumulation and gene expression.
AB  - Results of previous studies indicate that culture of preimplantation mouse
      embryos in SOM medium containing 85 mM NaCl promotes better development in vitro,
      as well as supporting higher rates of protein synthesis, when compared to culture
      in SOM containing 125 mM NaCl (Anbari and Schultz, 1993, Mol Reprod Dev 35:24-28;
      Biggers et al., 1993, Mol Reprod Dev 34:380-390). In the present study we compare
      the effect of culturing embryos in these 2 media on several aspects of RNA
      synthesis and gene expression in order to determine whether the reduced
      development in SOM containing 125 mM NaCl and lower rates of protein synthesis
      are correlated with decreases in RNA synthesis and stability and changes in gene
      expression. Although no apparent differences in the metabolism of [3H]uridine to
      UMP, UDP, and UTP and its incorporation into total RNA are observed when 2-cell
      embryos are cultured to the morula stage in either medium, a 20% decrease in the
      rate of mRNA synthesis is found when embryos are cultured in SOM containing 125
      mM NaCl. In addition, pulse-chase experiments reveal that total mRNA is less
      stable when the embryos are cultured in SOM containing 125 mM NaCl. Using a
      reverse transcription-polymerase chain reaction to assay for changes in the
      relative amounts of specific mRNAs, the relative amounts of mRNAs for IGF-I and
      IGF-II and their cognate receptors are dramatically reduced in embryos cultured
      in SOM containing 125 mM NaCl, whereas only a mild reduction is observed in the
      relative amount of actin mRNA. In contrast, when freshly isolated morulae are
      cultured to the blastocyst stage in either of these 2 media, similar amounts of
      these mRNAs are observed. Last, high-resolution, 2-dimensional gel
      electrophoresis reveals significant changes in the pattern of protein synthesis
      when the embryos are cultured in SOM containing 125 mM NaCl. Results of these
      experiments suggest that culture of embryos in medium containing lower
      concentrations of NaCl that are normally present in various culture media results
      in higher rates of mRNA synthesis and greater mRNA stability. These changes in
      RNA synthesis may underlie, at least in part, the improved development in vitro
      that is fostered by SOM containing 85 mM NaCl.

PMID- 7521652
TI  - A pilot study of accelerated cyclophosphamide, epirubicin and 5-fluorouracil plus
      granulocyte colony stimulating factor as adjuvant therapy in early breast cancer.
AB  - 32 consecutive early breast cancer patients were treated to evaluate the
      feasibility of an accelerated CEF regimen (cyclophosphamide 600 mg/m2, epirubicin
      60 mg/m2 and 5-fluorouracil 600 mg/m2) given intravenously every 2 weeks for six
      cycles together with granulocyte colony stimulating factor, 5 micrograms/kg/day
      subcutaneously from day 4 to day 11. One hundred and eighty two out of 192
      planned cycles (95%) were administered. Toxicity was mild: no cases of grade IV
      non-haematological toxicity and only one episode of grade IV granulocytopenia
      were observed. Delays or dose reductions of anti-neoplastic drugs occurred in 14
      cycles (7.7%). The mean duration of six cycles of treatment was 71 days (planned
      70) and 93% of average planned dose intensity was actually administered. The
      short course CEF therapy is a feasible, well tolerated outpatient chemotherapy
      regimen, allowing a 46% increase in dose intensity compared with a standard CEF
      regimen given every 3 weeks. A randomised study comparing this regimen to a
      standard CEF regimen is now in progress in early breast cancer patients.

PMID- 7521653
TI  - Is there potential for granulocyte or granulocyte-macrophage colony stimulating
      factors in radiotherapy?
AB  - The purpose of this communication was to explore which situations in radiotherapy
      might benefit from concomitant administration of haematopoietic growth factors
      (HGF). Only large-field radiotherapy is likely to induce bone marrow depression,
      such as irradiation of Hodgkin's disease. Therefore, we studied 122 patients
      irradiated for Hodgkin's disease, looking at peripheral blood cell count before,
      during and after the treatment. One hundred and four treatments were preceded by
      chemotherapy (MOPP and/or ABVD) and the radiation dose was between 36 and 44 Gy
      in 2 Gy per fraction sessions. Severe leucopenia (grade III WHO) was very
      uncommon and justified treatment interruption only twice. In both cases, it was
      paired with thrombocytopenia. No infection developed. It is concluded that when
      radiotherapy is used alone, prophylactic use of HGFs does not seem justified.
      This, of course, does not apply to radiochemotherapy combinations, although
      thorough investigations in this field are still awaited.

PMID- 7521654
TI  - Dose intensification in the treatment of patients with testicular germ cell
      tumours.

PMID- 7521651
TI  - CYFRA 21-1, a sensitive and specific new tumour marker for squamous cell lung
      cancer. Report of the first European multicentre evaluation. CYFRA 21-1
      Multicentre Study Group.
AB  - The present study was designed to determine whether CYFRA 21-1, measuring
      cytokeratin 19, could be a specific and sensitive tumour marker for non-small
      cell lung cancer (NSCLC). Serum measurements were made at diagnosis in 2250
      patient samples by an immunoradiometric "sandwich type" assay, using two
      cytokeratin 19 specific monoclonal antibodies. Among healthy individuals (n =
      711) and patients with benign lung disease (n = 546), 95 percentiles were 1.2 and
      2.95 ng/ml, respectively. Cumulative distribution analysis curves were
      established. From these data, 3.3 ng/ml gave 96% specificity. Using this cutoff,
      the sensitivity for small cell lung cancer was 16% (n = 74) compared to 41% for
      NSCLC (n = 547). In histological sub-groups, sensitivity was 57% for squamous
      cell lung cancer, 34% for undifferentiated large cell carcinoma and 27% for
      adenocarcinoma, the level of CYFRA 21-1 was correlated with tumour size and UICC
      stage. In squamous cell lung cancer, the sensitivity of the squamous cell
      carcinoma marker was 30%, 25% for carcinoembryonic antigen and 46% for tissue
      polypeptide antigen, using the same series of samples and cutoffs defined at 96%
      specificity. In conclusion, CYFRA 21-1 is a sensitive tumour marker for NSCLC,
      especially squamous cell lung cancer.

PMID- 7521655
TI  - [Lesions of the little finger in Dupuytren's disease].
AB  - One hundred and twenty six patients (148 hands) with Dupuytren's disease of the
      fifth finger were reviewed with an average follow-up of 5 years. Twenty-nine
      dermo-fasciectomies were performed on the palmar area of the fifth finger. The
      improvement in the MP joint was complete in all cases. A classification in to 4
      grades according to the degree of pre- and postoperative retraction is proposed.
      The average improvement at the PIP joint was 50 degrees. 26 recurrences were
      observed. The recurrence rate was similar with or without a skin graft but the
      functional result was better with a digital graft, as recurrences were located
      away from the PIP joint.

PMID- 7521656
TI  - [Results of the primary repair of the collateral palmar digital nerves].
AB  - The aim of this study was to analyse the results of primary collateral digital
      nerve repair as a function of several factors: age, surgeon's experience, type of
      lesion and associated lesions, etc. The conclusions are based on a homogeneous
      series of 64 patients with 83 nerve lesions treated by primary microsurgical
      nerve repair with a follow-up of at least one year.

PMID- 7521659
TI  - Attritional rupture of the extensor tendon due to longstanding Kienbock's
      disease.
AB  - Two cases of attritional rupture of the extensor tendon due to longstanding
      Kienbock's disease are reported. The rupture was caused by the fragment of a
      collapsed lunate which pierced the dorsal capsule of the wrist.

PMID- 7521657
TI  - [Carpal tunnel syndrome and amyloid tenosynovitis in patients undergoing chronic
      hemodialysis. Evaluation and treatment apropos of 130 cases].
AB  - Over a 12-year period (1979-1991), 130 carpal tunnel syndromes were diagnosed in
      89 haemodialysed renal failure patients, representing 17% of all haemodialysed
      patients followed over the same period. 6% of patients had been haemodialysed for
      less than 5 years (mean duration of dialysis: 10.4 years). 25% of cases had a
      trigger finger and 21 out of 89 patients had amyloid arthropathy. No precise
      relationship was detected between the side of the carpal tunnel syndrome and the
      side of the arteriovenous fistula. In 130 cases, release of the median nerve and
      wide tenosynovectomy of the flexor tendons were performed under pneumatic
      tourniquet except in the case of a prosthetic shunt. Tenosynovial amyloid
      deposits were found in 84% of cases. The mean postoperative follow-up was 40
      months (range: 6 to 120 months). Postoperatively, the acroparaesthesiae
      disappeared in 93% of cases. 79% of cases with a sensory defect obtained sensory
      recovery, versus 27% of cases with a motor deficit for motor recovery. In 20% of
      the 130 cases, decreased digital mobility was observed postoperatively due to
      extension of the tenosynovitis to the fingers. Four cases of recurrence were
      observed.

PMID- 7521661
TI  - [The role of posterior bracket plate osteosynthesis in the treatment of
      compression-extension fractures of the distal end of the radius].
AB  - Osteosynthesis without immobilisation of compression-extension fractures by means
      of a posterior plate was studied in prospective series with a minimum follow-up
      of six months (first group: 73 patients) and a minimum follow-up of one year
      (second group: 63 patients). The clinical results were evaluated and showed
      several complications (no infection, but reflex sympathetic dystrophy,
      paresthesia, unsightly scars). The clinical and radiological findings (radio
      ulnar index) could improve with several technical devices, now used.

PMID- 7521660
TI  - The narrative of my early experience in microsurgery (Algimentas Narakas: 1927
      1993).

PMID- 7521658
TI  - [Recent fractures of the base of the 1st metacarpal bone. A study of a series of
      138 cases].
AB  - Fractures on the base of the first metacarpal are uncommon lesions, affecting
      young subjects and have major social repercussions (an average of 3.5 months off
      work). The authors have analysed the clinical and radiological results of a
      series of 138 recent fractures of the base of the first metacarpal with a mean
      follow-up of 7 years (12 month-14 years). They used a classification into 5 types
      (Bennett's with a large fragment = 22%, Bennett's with a small fragment = 20%,
      Rolando = 15%, extraarticular fractures = 36%, Comminuted fractures = 6%) which
      are easy to recognize on standard x-rays, or preferably on Kapandji views,
      allowing a standardized therapeutic approach. 70% of patients were younger than
      40 and in one half of cases the causal accident was a motor vehicle accident. 12%
      of fractures were open and 45% were associated with other traumatic lesions. In
      this series, 35% of cases were treated orthopedically, 57% according to Iselin's
      technique, 5% by direct osteosynthesis and 3% by external fixation with a mean
      immobilization of 40 days. A number of clinical and radiological criteria were
      studied in the 88 patients reviewed. A 100-point grading system was established
      and, independent of the type of treatment, the authors obtained 61% of very good
      results, 23% of good results, 12% of moderate results, 2% of poor results and 2%
      of very poor results. Articular lesions constituted a factor of severity and
      failure to respect opening of the commissure appeared to be more pejorative than
      a small imperfection of reduction. The authors noted that simple treatment
      according to Iselin's technique still has many indications despite progress in
      miniaturized osteosynthesis.

PMID- 7521663
TI  - Hydration in the terminally ill patient.
AB  - Dehydration is considered by many health professionals to be painful and
      uncomfortable, and the use of intravenous fluids is often advocated to maintain
      hydration in the dying patient. This article examines the issue of hydration in
      the terminally ill patient from a theoretical, practical, ethical and legal
      standpoint and suggests that dehydration may in fact be beneficial to the comfort
      of the dying patient.

PMID- 7521664
TI  - The Standard guide to public speaking.

PMID- 7521665
TI  - The role of the L-arginine: nitric oxide pathway in circulatory shock.

PMID- 7521666
TI  - Processing requirements of two acetylcholine receptor derived peptides for
      binding to antigen presenting cells and stimulation of murine T cell lines.
AB  - We have previously identified two myasthenogenic T cell epitopes of the human
      acetylcholine receptor (AChR) alpha subunit, peptides p195-212 and p259-271.
      These peptides were the immunodominant T cell epitopes of AChR in SJL and BALB/c
      mice respectively, and only cryptic in C3H.SW strain. In order to find out
      whether these mouse strains differ in their requirements for processing of the
      same T cell epitopes, we used p195-212 specific T cell lines from SJL, TCSJL195
      212, and C3H.SW, TCSW195-212, mice, and p259-271 specific T cell lines from
      BALB/c, TCBALB/c259-271, and C3H.SW, TCSW259-271, mice. The peptide-specific
      proliferative responses of the lines TCSW195-212 and TCSW259-271, originated from
      strains in which these peptides are cryptic epitopes, were inhibited
      significantly in the presence of several inhibitors of proteases or
      glutaraldehyde-fixed antigen presenting cells (APC). In contrast, the
      proliferative responses of the lines TCSJL195-212 and TCBALB/c259-271,
      established from strains in which these peptides are immunodominant, were only
      slightly affected by the above inhibitors or by fixation of the APC. Using a
      direct binding assay of biotinylated peptides to live intact APC, we showed that
      peptides p195-212 and p259-271 preserved their binding capacity to APC of SJL and
      BALB/c mice respectively when processing was inhibited. Thus, the AChR peptides
      that represent cryptic T cell epitopes have to be processed before they can be
      recognized by T cells, whereas no further processing is necessary for APC
      presentation and T cell stimulation when these peptides are immunodominant
      epitopes.

PMID- 7521662
TI  - Autologous bone marrow transplantation in poor-risk high-grade non-Hodgkin's
      lymphoma in first complete remission. Newcastle and Northern Lymphoma Group.
AB  - We report the safety and efficacy of autologous bone marrow transplantation
      (ABMT) in 30 patients with high-grade non-Hodgkin's lymphoma (NHL) in first
      complete remission (CR1) following remission induction chemotherapy. Two patients
      relapsed prior to ABMT. All patients were conditioned with high-dose melphalan.
      In Addition, ten received fractionated total body irradiation, one hemi-body
      irradiation and four high-dose etoposide. Unmanipulated non-cryopreserved
      autologous marrow was reinfused within 56 h of harvesting. Engraftment occurred
      in all patients with a median of 11 days of neutropenia (< 0.5 x 10(9) l-1), a
      median requirement for platelet transfusion of 3 days and packed red cell
      transfusion of 2 units, with a median hospital stay of 18 days post transplant.
      There was no procedure-related mortality and only minor morbidity was observed.
      Two patients relapsed at 1 and 2 months post transplantation, and one patient
      died of carcinoma of the lung 33 months after transplantation. The remaining 25
      patients remain alive, well and in CR1 with a median follow-up of 44 months. The
      event-free survival at 3 years for all patients considered for ABMT was 83%. We
      conclude that ABMT for high-grade NHL in CR1 with non-cryopreserved marrow
      results in rapid haematological recovery without growth factor support. It is
      safe and is associated with high survival when used as consolidation of CR in
      high-risk patients.

PMID- 7521667
TI  - Anti-CD48 (murine CD2 ligand) mAbs suppress cell mediated immunity in vivo.
AB  - With the identification of murine CD48 as a homolog of the human CD2 ligand LFA-3
      (CD58) and as a ligand itself for murine CD2, the anti-murine CD48 mAb HM48-1 was
      administered intravenously to investigate the role of CD48 in cell mediated
      immunity in vivo. Anti-CD48 mAb diminished the contact sensitivity response to
      the hapten trinitrophenol (TNP). mAb also inhibited in vivo priming for the
      subsequent generation of secondary, TNP-specific, cytotoxic T lymphocytes (CTL)
      in vitro. The inhibitory effect was most effective in the afferent or inductive
      phase of immunity for CTL, while anti-CD48 mAb was most inhibitory for the
      efferent or elicitative phase of contact sensitivity. Addition of anti-CD48 mAb
      directly to secondary CTL cultures also completely inhibited CTL generation,
      while addition to the lytic assay showed only minimal inhibition of CTL activity.
      Combining cells from mAb treated and untreated animals showed no evidence for
      suppressor cells. Further experiments revealed that mAb administered in vivo, as
      well as to culture, inhibited development of primary, alloantigen-specific CTL in
      vitro. Mixed lymphocyte reaction and phytohemagglutinin proliferation were
      partially suppressed by mAb administered in vivo or in vitro, whereas other
      mitogenic responses remained unaffected. Flow cytometric analysis revealed a
      moderate down modulation of CD48, CD3 and CD8 after treatment with anti-CD48.
      However, this did not represent T cell depletion since CD2, Thy-1.2 and Ig
      expression did not change. These results support a major unrecognized role for
      CD48 in diverse aspects of cell mediated immunity, affecting both CD4+ and CD8+
      effector T cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521668
TI  - Direct binding of autoimmune disease related T cell epitopes to purified Lewis
      rat MHC class II molecules.
AB  - New strategies applied in the treatment of experimental autoimmune disease models
      involve blocking or modulation of MHC-peptide-TCR interactions either at the
      level of peptide-MHC interaction or, alternatively, at the level of T cell
      recognition. In order to identify useful competitor peptides one must be able to
      assess peptide-MHC interactions. Several well described autoimmune disease models
      exist in the Lewis rat and thus this particular rat strain provides a good model
      system to study the effect of competitor peptides. So far no information has been
      available on the peptide binding characteristics of the Lewis rat MHC class II
      RT1.B1 molecule. We have now developed a biochemical binding assay which enables
      competition studies in which the relative MHC binding affinity of a set of non
      labelled peptides can be assessed while employing detection of biotinylated
      marker peptides by chemiluminescence. The assay is sensitive and specific. We
      have used this assay to determine the binding characteristics of several disease
      associated T cell determinants and their sequence analogues in the Lewis rat.
      Notably, most of the autoimmune disease associated peptide sequences tested were
      found to be intermediate to poor binders. Single amino acid substitutions at
      defined positions were sufficient to turn certain peptides into good binders.
      These results are relevant to the design of competitor peptides in the treatment
      of experimental autoimmune diseases.

PMID- 7521669
TI  - Reversal of T cell unresponsiveness by augmentation of antigen presenting cell
      function.
AB  - We have previously described epitopes of the 18 kDa protein of Mycobacterium
      leprae which stimulate T and B cell responses in different strains of mice. A
      series of overlapping 20-mer peptides that span the 18 kDa protein were used as
      immunogens to examine T and B cell recognition of different epitopes. Strain
      specific variation in the epitopes which induce the strongest responses was
      affected by genes linked to the H-2 complex and the T cell responses revealed by
      re-challenge with antigen were at least partially controlled by factors other
      than T cell specificity. We have examined the responses to one such antigen,
      peptide 1-20, which contains strongly immunogenic epitopes for T and B cells. T
      cells from draining lymph nodes of peptide 1-20 immunized B10.BR, but not BALB/c
      mice, proliferated in vitro in response to rechallenge with peptide 1-20 or whole
      protein. Immunization with the same peptide also induced specific antibody only
      in B10.BR mice. However, immunization of BALB/c mice results in 'silent' priming
      of T cells since these can be induced to respond in vitro to this antigen when
      cultured with activated macrophages as antigen presenting cells (APC). The
      failure of APC from mBALB/c mice primed with peptide 1-20 to stimulate CD4+
      proliferation when re-challenged in vitro and the failure to elicit antibody
      responses to peptide 1-20 are presumably due to the same defect in antigen
      presenting cell function, since presentation of peptide 1-20 by activated
      macrophages is sufficient to restore both responses.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7521671
TI  - Aims and results of palliative radiotherapy in urological cancer.
AB  - Many patients with urological cancer will need palliative treatment during the
      clinical course of their disease. Although we believe that radiotherapy gives
      symptom relief in many of these patients, surprisingly few studies have been
      published that specifically evaluate the symptomatic effects of radiation.
      Furthermore, optimal fractionation regimens and total doses are uncertain. Future
      clinical trials should focus on these issues.

PMID- 7521670
TI  - Vaccination of the Leishmania major susceptible BALB/c mouse. I. The precise
      selection of peptide determinant influences CD4+ T cell subset expression.
AB  - BALB/c mice are susceptible to cutaneous leishmaniasis upon infection with
      Leishmania major while C57BL/6 are not. There is a major promastigote surface
      protease (PSP or gp63) which is available in both native and recombinant forms,
      and for which the primary amino acid sequence is known. Immunization with PSP has
      been shown to offer some protection against challenge with the live organism.
      Therefore, we attempted to develop a peptide vaccine with PSP peptides. In the
      first experiments, recall proliferative responses to PSP were measured using a
      set of 15mer peptides spanning the entire PSP molecule which allowed designation
      of major determinant regions in BALB/c, C57BL/6, and CBA mice. Several of these
      determinants were promiscuous and shared almost the identical core amino acid
      residues in the different strains. Immunization with major determinant peptides
      was recalled vigorously with L. major soluble antigen as well as with PSP. The
      response to peptide was almost entirely Th1 as measured by a localized ELISA
      assay for single-cell production of IFN-gamma. A similar assay for IL-5, which
      overcomes problems of sensitivity and inhibition by lymphokines produced by Th1
      cells, indicates very little production of Th2 cells even by BALB/c. It was found
      that if a major responsive peak was examined by recall with overlapping peptides,
      the highest, central peptide gave a mainly Th1 response while the boundary, less
      efficient peptides gave more of a Th2 response. Possible reasons for this were
      discussed. These results point to the importance of selecting the exactly
      appropriate peptide in considering a vaccinogen that might protect susceptible
      individuals. Even the choice of a somewhat immunogenic peptide within the
      determinant envelope might actually exacerbate infection by steering the response
      in a Th2 direction.

PMID- 7521672
TI  - Erysipelas in neutropenia of unknown origin, successfully treated with r-metHuG
      CSF (filgrastim)

PMID- 7521673
TI  - Cholesterol and serotonin: seeking a possible link between blood cholesterol and
      CSF 5-HIAA.

PMID- 7521674
TI  - Oxytocin gene expression and oxytocin immunoactivity in the ovary of the common
      marmoset monkey (Callithrix jacchus).
AB  - Oxytocin was identified in ovaries recovered on Day 5 (+/- 1) of the luteal phase
      from three female marmoset monkeys (Callithrix jacchus). With use of a reverse
      transcription-polymerase chain reaction assay, expression of mRNA for oxytocin
      and oxytocin receptor was detected in both luteal tissue and in the ovarian
      remnant. Evidence for ovarian synthesis of oxytocin was provided by
      immunohistochemistry, which showed positive staining for oxytocin and neurophysin
      in the cytoplasm of the luteal cells. Some luteal cells had a more intensely
      stained perinuclear region than others for oxytocin immunoreactivity, whereas the
      staining for neurophysin was evenly distributed. Granulosa and theca cells of
      antral follicles also showed positive staining for oxytocin immunoreactivity; no
      reactivity was found in fibroblast or endothelial cells. Oxytocin
      immunoreactivity was also detected in the luteal tissue of all animals by
      immunoassay, with values ranging from 2.8 to 12.1 ng/g wet weight. The oxytocin
      concentration for the ovarian remnant was either very low (0.55-0.75 ng/g wet
      weight) or nondetectable (< 0.5 ng/g wet weight). Local production of oxytocin
      within the ovary was suggested by the measurement of higher oxytocin
      concentrations in the blood from ovaries containing corpora lutea compared with
      peripheral blood. Collectively, these results provide evidence for ovarian
      biosynthesis of oxytocin and suggest the possibility of a paracrine role in the
      regulation of primate ovarian function.

PMID- 7521675
TI  - Oocytic tumor necrosis factor alpha: localization in the neonatal ovary and
      throughout follicular development in the adult rat.
AB  - Tumor necrosis factor alpha (TNF alpha) has previously been immunolocalized
      within mouse oocytes. Our first objective was to examine TNF alpha
      immunolocalization in ovaries of adult, fetal, and neonatal rats. Our second
      objective was to examine TNF alpha mRNA in ovaries by Northern blot analysis and
      in oocytes by reverse-transcriptase polymerase chain reaction (RT-PCR). Our final
      objective was to determine whether oocytes contained bioactive TNF alpha. Ovaries
      and oviducts were collected throughout the estrous cycle in adult rats, fetal
      ovaries were obtained 1 day before expected delivery, and neonatal ovaries were
      collected 2 days after birth. TNF alpha was localized in tissues by a biotin
      avidin immunocytochemical procedure. Immunocytochemistry in adult ovaries showed
      that the ooplasm of the oocyte was the primary site of TNF alpha localization
      within the follicle. Immunostaining was present in all oocytes in the adult,
      including ovulated oocytes within the oviduct. Oocytic TNF alpha immunostaining
      was also present within oocytes in the neonate; however, fetal oocytes did not
      contain immunoreactive TNF alpha. Northern blots showed that ovaries in the
      adult, neonate, and fetus all contained TNF alpha mRNA. RT-PCR analysis of
      oocytes collected from preovulatory follicles generated a cDNA band of 500 bp,
      corresponding to the predicted size for amplified TNF alpha cDNA. Subsequent
      Southern blot analysis showed that the 500-bp band hybridized to the TNF alpha
      probe, indicating that preovulatory oocytes contain TNF alpha mRNA. Preovulatory
      oocytes were used in TNF alpha cytotoxicity assays with L929 cells. Oocytes
      contained TNF alpha bioactivity that was similar to that of recombinant murine
      TNF alpha in the bioassay. Our results provide evidence for the identification of
      immunoreactive and bioactive TNF alpha within oocytes in the rat, which is
      further supported by the presence of TNF alpha mRNA within the oocyte. These
      studies also indicate that TNF alpha may appear in the oocyte around the time of
      birth.

PMID- 7521676
TI  - Tenascin in pregnant and non-pregnant rat uterus: unique spatio-temporal
      expression during decidualization.
AB  - Tenascin is a large extracellular matrix (ECM) protein generally restricted to
      developing embryonic tissues and tissues undergoing remodelling in the adult, but
      it has been suggested that tenascin is immunomodulatory. In this study we have
      used indirect immunofluorescence to investigate the distribution of tenascin
      within the uteri of pregnant and non-pregnant rats. The non-pregnant uterus
      expressed tenascin in the stroma around the glands, but only the subluminal
      stroma showed cyclical variations. Dependence of the latter on progesterone was
      verified in ovariectomized animals supplemented with steroid hormones. During
      early pregnancy, the uterine circular smooth muscle maintained an intense
      expression of tenascin. In the decidualizing endometrium, tenascin expression
      showed dramatic changes that reflected the regionalization of the decidualization
      process. On Day 6 (blastocyst attachment), tenascin immunoreactivity was
      prominent in the primary decidualization zone immediately surrounding the
      conceptus. On Day 7, expression had increased within the secondary decidua that
      had developed throughout the antimesometrial endometrium. By Day 8, the
      antimesometrial decidua showed diminished tenascin immunoreactivity; expression
      became largely confined to the ECM of the developing decidua in the mesometrial
      region, where levels were high. On Day 10, the well-developed mesometrial decidua
      was negative. Interestingly, tenascin expression was up-regulated in the walls of
      the vessels in the metrial gland within the mesometrial triangle beginning on Day
      10 of pregnancy. From these studies we conclude that tenascin expression may be
      an important reflection of the dynamics involved with tissue restructuring during
      early pregnancy and may play a role in immunomodulation, since expression of this
      protein in the mesometrial decidua coincides with the presence of differentiating
      natural killer cell lineage lymphocytes in the same region.

PMID- 7521678
TI  - Testis-specific RT7 protein localizes to the sperm tail and associates with
      itself.
AB  - The RT7 gene recently cloned by us is expressed as an abundant RNA in round
      spermatids. In vitro transcription-translation showed that the RT7 gene encodes a
      protein of 26-27 kDa on SDS-polyacrylamide gels. Here we report the development
      of monoclonal antibodies (mAbs) raised against a peptide from the predicted N
      terminal amphipathic alpha-helix of the rat RT7 protein. All mAbs recognize RT7
      protein or N-terminal parts of it. To investigate RT7 in vivo, mAbs were used in
      immunofluorescence microscopy and confocal laser immunofluorescence microscopy.
      Several mAbs recognize RT7 protein in elongating spermatids: the observed
      staining pattern suggests a nonrandom localization in these cells. Two mAbs
      recognize the protein only in sperm tails. Using co-immunoprecipitation assays,
      we found that RT7 can form stable complexes with itself that are associated
      through a region located in the N-terminal half of RT7. Our results identify the
      RT7 protein as a major sperm tail component and suggest that it may be a
      structural component of sperm tail outer dense fibers (ODF).

PMID- 7521677
TI  - Response of alpha 2-macroglobulin messenger ribonucleic acid expression to acute
      inflammation in the testis is different from the response in the liver and brain.
AB  - Recent studies from this laboratory have shown that Sertoli cells derived from 20
      day-old rats and cultured in vitro synthesize and secrete a nonspecific protease
      inhibitor that is structurally and immunologically similar to serum alpha 2
      macroglobulin (alpha 2-MG). In contrast to its serum homologue, the testicular
      alpha 2-MG is not an acute-phase protein in the rat since its protein
      concentration in the rete-testis fluid does not increase in response to
      inflammation. In the present study we examined the expression of alpha 2-MG mRNA
      in the rat testis in comparison to that in the brain and liver following induced
      inflammation. alpha 2-MG mRNA in the testis did not respond to induced
      inflammation, whereas its protein concentration in serum and its mRNA level in
      the brain and liver increased significantly in 20-day-old inflamed rats. In 8-day
      old rat testis, where the blood-testis barrier is not yet formed, alpha 2-MG mRNA
      expression also did not respond to induced inflammation. The mRNA expression of
      clusterin, another authentic Sertoli cell protein whose secretion appears to be
      closely related to cell-cell interactions in the seminiferous epithelium, was
      shown to be unaffected by induced inflammation in the testis, brain, and liver.
      In view of the unexpected differential expression of alpha 2-MG mRNA to induced
      inflammation in the testis and liver, we sought to examine whether Sertoli cell
      alpha 2-MG would respond to FSH and testosterone (T), the major regulators of
      testicular function. Interestingly, expression of alpha 2-MG and clusterin mRNA
      in the Sertoli cell was not regulated by FSH, T, or a combination of FSH and T.
      Since there is an intimate morphological relationship between Sertoli cells and
      germ cells, we next examined the effect of germ cell-conditioned medium (GCCM) on
      Sertoli cell alpha 2-MG and clusterin mRNA expression. It was noted that GCCM
      caused a dose-dependent stimulation of alpha 2-MG and inhibition of clusterin
      mRNA expression in Sertoli cells, respectively. Therefore, our studies have shown
      that the regulatory mechanism that modulates the expression of alpha 2-MG mRNA in
      the rat testis is different from its counterpart in the brain and liver.

PMID- 7521679
TI  - Identification of AMPA receptors in catfish electroreceptor organs.
AB  - Single afferent unit recording in microampullae of the catfish revealed that bath
      applied AMPA increases both resting discharge frequency and electrically evoked
      responses. The potency of AMPA is of the order of 10 microM. DNQX strongly
      inhibits the excitatory effects of AMPA. The results suggest the presence of AMPA
      receptors at the synaptic membrane of ampullary electroreceptor organs in the
      catfish.

PMID- 7521680
TI  - Microwave antigen retrieval of beta-amyloid precursor protein immunoreactivity.
AB  - Formalin fixation reduces beta-amyloid precursor protein (beta APP)
      immunoreactivity which restricts its study in archival tissue. Formic acid
      pretreatment has previously been used in an attempt to overcome this problem, but
      makes the sections very friable. In the present study, a microwave antigen
      retrieval method has been compared with formic acid pretreatment for retrieving
      beta APP immunoreactivity in formalin-fixed, paraffin-embedded human brain
      tissue. Microwave treatment resulted in superior retrieval of beta APP
      antigenicity in dystrophic neurites in Alzheimer's disease and in injured axons
      after head injury, using antibodies to three different epitopes. Unlike formic
      acid, microwave treatment causes minimal adverse effects on the strength and
      slide adhesion of the sections.

PMID- 7521683
TI  - Target cells modulate dopamine transporter gene expression during brain
      development.
AB  - We have analysed the expression of the dopamine transporter (DAT) gene and
      compared it with that of tyrosine hydroxylase, neuronal GABA transporter and
      synaptic vesicle monoamine transporter genes during pre- and post-natal
      development of rat mesencephalic dopaminergic (DA) neurones. Our results show
      that DAT transcripts are not detectable until embryonic day (E) 15, whilst those
      of the other genes analysed are already present at E12. In vitro, the level of
      DAT gene transcription in mesencephalic E13 DA neurones is increased in coculture
      with target striatal cells. Thus striatal targets cells regulate, at the
      transcriptional level, a key step of dopaminergic neurotransmission during DA
      neurone development.

PMID- 7521681
TI  - Alteration by Iloprost of the vasospastic effects of endothelin-1 in rabbit
      cerebral vessels.
AB  - The reversal of endothelin-1 induced cerebral vasospasm with Iloprost was studied
      in the rabbit. Vasospasm in the basilar artery was evaluated by angiography;
      cerebral ischaemia by 'red-neurone-count' on light microscopy and morphological
      changes by electron microscopy. A potent antagonistic effect of Iloprost against
      ET-1 was observed in each of the parameters measured.

PMID- 7521684
TI  - Expression of a paired helical filament tau epitope in embryonic chicken central
      nervous system.
AB  - Immunoblots from embryonic chicken optic lobes (midbrain) and spinal cord were
      found to contain different proteins with a molecular weight between 45 and 70 kDa
      that are recognized by monoclonal antibodies (mAbs) directed at human tau
      proteins. Each appears as a doublet on SDS-PAGE. The upper, slower migrating
      bands were recognized by AT8, a monoclonal antibody that requires a
      phosphorylated Ser-202, an epitope specific for abnormally phosphorylated tau of
      paired helical filaments (PHF-tau) in Alzheimer brains. The corresponding faster
      migrating bands were stained by the mAbs BT2 and tau-1, both requiring an epitope
      containing a non-phosphorylated Ser-202. Phosphatase treatment abolished binding
      of AT8 and induced an additional binding of tau-1 (and BT2) to the upper bands.
      Thus, the data suggest that in embryonic chicken central nervous system Ser-202
      occurs in a phosphorylated and in a non-phosphorylated state in several distinct
      tau isoforms.

PMID- 7521682
TI  - Hippocampal in vitro kindling is not blocked by nitric oxide synthase inhibitors.
AB  - Effects of nitric oxide synthase (NOS) inhibitors on the induction of an in vitro
      model of kindling were investigated in the rat hippocampal slice. It has been
      reported that NMDA receptor activation stimulates NOS and guanosine 3',5'-cyclic
      monophosphate (cGMP) production and that the interruption of this pathway
      interferes with LTP in the CA1 hippocampal field. Because the induction of LTP
      and kindling both involve NMDA receptor activation, we tested the effects of NOS
      inhibitors on the genesis and initial rate of interictal-like spontaneous bursts
      in CA1 and CA3 of the rat hippocampal slice. Experimental groups were exposed to
      100 microM methyl-L-arginine (active NOS inhibitor), nitro-L-arginine (active NOS
      inhibitor), or methyl-D-arginine (inactive isomer of the NOS inhibitor) for 1 h
      prior to in vitro kindling. These results indicate that rather than preventing
      the induction of kindling in this model of epileptogenesis, NOS inhibition may
      facilitate the initiation of interictal-like spontaneous bursts in the rat
      hippocampal slice.

PMID- 7521685
TI  - Tyrosine phosphorylation of CRKL in Philadelphia+ leukemia.
AB  - The chimeric BCR/ABL protein is characteristic of Philadelphia (Ph)+ leukemia
      because it is the direct product of the Ph translocation and it has been shown to
      play a causal role in the genesis of leukemia. The BCR/ABL protein exhibits a
      deregulated tyrosine-kinase activity capable of phosphorylating different
      cellular substrates in vivo and in vitro. CRKL, an adaptor protein consisting of
      SH2 and SH3 domains in the absence of a catalytic domain, is one potential in
      vivo substrate of BCR/ABL. Previous experiments have shown that CRKL is
      phosphorylated on tyrosine in the chronic myelogenous leukemia (CML) cell line
      K562 and that CRKL is a substrate for ABL and for BCR/ABL in COS-1 cells. In the
      current study, we show that in peripheral blood cells a direct correlation exists
      between the presence of BCR/ABL and the phosphorylation status of CRKL. In Ph-
      peripheral blood cells, CRKL is present only in the nonphosphorylated form. In
      contrast, all BCR/ABL+ CML and acute lymphoblastic leukemia patient samples
      examined showed clear tyrosine-phosphorylation of CRKL. This result strongly
      suggests that CRKL is a biologically significant substrate for BCR/ABL and is
      likely to play a major role in the development of Ph+ leukemia.

PMID- 7521686
TI  - Mice lacking granulocyte colony-stimulating factor have chronic neutropenia,
      granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil
      mobilization.
AB  - Mice lacking granulocyte colony-stimulating factor (G-CSF) were generated by
      targeted disruption of the G-CSF gene in embryonal stem cells. G-CSF-deficient
      mice (genotype G-CSF-/-) are viable, fertile, and superficially healthy, but have
      a chronic neutropenia. Peripheral blood neutrophil levels were 20% to 30% of wild
      type mice (genotype G-CSF+/+) and mice heterozygous for the null mutation had
      intermediate neutrophil levels, suggesting a gene-dosage effect. In the marrow of
      G-CSF-/- mice, granulopoietic precursor cells were reduced by 50% and there were
      reduced levels of granulocyte, macrophage, and blast progenitor cells. Despite G
      CSF deficiency, mature neutrophils were still present in the blood and marrow,
      indicating that other factors can support neutrophil production in vivo. G-CSF-/-
      mice had reduced numbers of neutrophils available for rapid mobilization into the
      circulation by a single dose of G-CSF. G-CSF administration reversed the
      granulopoietic defect of G-CSF-/- mice. One day of G-CSF administration to G-CSF
      /- mice elevated circulating neutrophil levels to normal, and after 4 days of G
      CSF administration, G-CSF+/+ and G-CSF-/- marrows were morphologically
      indistinguishable. G-CSF-/- mice had a markedly impaired ability to control
      infection with Listeria monocytogenes, with diminished neutrophil and delayed
      monocyte increases in the blood and reduced infection-driven granulopoiesis.
      Collectively, these observations indicate that G-CSF is indispensible for
      maintaining the normal quantitative balance of neutrophil production during
      "steady-state" granulopoiesis in vivo and also implicate G-CSF in "emergency"
      granulopoiesis during infections.

PMID- 7521687
TI  - Substitutions and deletions in the cytoplasmic domain of the phagocytic receptor
      Fc gamma RIIA: effect on receptor tyrosine phosphorylation and phagocytosis.
AB  - Fc gamma RIIA in the absence of other Fc receptors or receptor subunits induces
      the ingestion of IgG-coated cells. The cytoplasmic domain of Fc gamma RIIA
      contains two Y-x-x-L sequences similar to those in other Ig gene family receptors
      plus an additional tyrosine residue not in a Y-x-x-L motif. Upon cross-linking,
      Fc gamma RIIA is phosphorylated on tyrosine and the cytoplasmic tyrosines, Y275
      (Y1), Y282 (Y2), and Y298 (Y3), may be important for its phagocytic activity.
      Because COS-1 cells can serve as a model for examining molecular structures
      involved in phagocytosis, substitutions and deletions were introduced into the
      cytoplasmic domain of Fc gamma RIIA and examined in COS-1 cell transfectants for
      their effects on phagocytosis and tyrosine phosphorylation. Disruption of a
      single cytoplasmic Y-x-x-L motif by substitution of tyrosine Y2 or Y3 by
      phenylalanine or by removing the threonine and leucine residues within the motif
      inhibited phagocytosis 50% to 65%. Tyrosine phosphorylation of Fc gamma RIIA also
      was inhibited, although to a greater extent by the substitution of Y3 than of Y2.
      Replacement of the N-terminal first cytoplasmic domain tyrosine, Y1, which is not
      within a typical Y-x-x-L, by itself did not inhibit phagocytosis, but replacement
      of Y1 in mutants lacking Y2 or Y3 virtually eliminated phagocytic activity and
      receptor tyrosine phosphorylation. Thus, at least two cytoplasmic tyrosines,
      including at least one typical single Y-x-x-L motif, are required for
      phagocytosis by Fc gamma RIIA. The data suggest that there is a close but not a
      simple relationship between phosphorylation of the Fc gamma RIIA cytoplasmic
      tyrosines and Fc gamma RIIA-mediated phagocytosis. Y3 appears to be particularly
      important because its removal by truncation or replacement with phenylalanine
      inhibits both tyrosine phosphorylation and phagocytosis in parallel. Alterations
      in the 12 residue proline-containing sequence between the two Y-x-x-L motifs also
      reduced phagocytic activity and tyrosine phosphorylation. Thus, the specific
      structure of the Fc gamma RIIA cytoplasmic domain accounts for its ability to
      stimulate phagocytosis in the absence of other subunits.

PMID- 7521688
TI  - Rapid activation of the STAT3 transcription factor by granulocyte colony
      stimulating factor.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates
      proliferation and differentiation of progenitor cells of neutrophils by signaling
      through its receptor (G-CSFR). Although the G-CSFR belongs to the cytokine
      receptor superfamily, which lacks an intracellular kinase domain, G-CSF-induced
      tyrosine phosphorylation of cellular proteins is critical for its biologic
      activities. We report here that JAK1 and JAK2 tyrosine kinases are tyrosine
      phosphorylated in response to G-CSF induction. We also demonstrate that the DNA
      binding protein STAT3 (also called the acute-phase response factor [APRF],
      activated by interleukin-6) is an early target of G-CSF-induced tyrosine
      phosphorylation. G-CSF induces two DNA-binding complexes; the major complex
      contains tyrosine phosphorylated STAT3 protein and the minor complex appears to
      be a heterodimer of the STAT1 (previously p91, a component of DNA-binding
      complexes activated by interferons) and STAT3 proteins. Antiphosphotyrosine
      antibody interferes with the DNA binding activity of activated STAT3, indicating
      that tyrosine phosphorylation of STAT3 is important for the DNA binding activity.
      These results identify a signal transduction pathway activated in response to G
      CSF and provide a mechanism for the rapid modulation of gene expression by G-CSF.

PMID- 7521689
TI  - Activation of Ras and formation of GAP complex during TPA-induced monocytic
      differentiation of HL-60 cells.
AB  - In this study, it was shown that the proportion of guanosine triphosphate (GTP)
      bound active Ras increased in TPA (12-o-tetradecanoyl phorbol-13-acetate)-induced
      monocytic differentiation of HL-60 cells. The increase of active Ras was observed
      at 24 hours after TPA stimulation and attained to threefold (15%) over the
      proportion in nontreated HL-60 cells. Herbimycin A, an inhibitor of tyrosine
      kinase, prevented the activation of Ras, as well as the induction of monocytic
      differentiation. In parallel with the activation of Ras, the proteins with
      molecular weights of 52, 56, 62, and 190 kD were tyrosine-phosphorylated and
      formed a complex with GTPase-activating protein (GAP) for Ras. In addition to the
      116-kD GAP (type I GAP), the 100-kD GAP (type II GAP) molecule was markedly
      induced at 24 hours after TPA stimulation of HL-60 cells. These phenomena
      sustained for a further 24 hours during monocytic differentiation. However, they
      were not observed during retinoic acid-induced granulocytic differentiation of
      the cells. The HL-60 transfectants, which expressed a dominant inhibitory Ha-ras
      Asn17, showed a low level of tyrosine-phosphorylated GAP-associated proteins and
      did not undergo full differentiation in response to TPA. Taken together, these
      data indicate that the activation of Ras and GAP complex formation mutually
      correlate and function downstream of protein-tyrosine kinases in the signaling
      pathway for monocytic differentiation of HL-60 cells.

PMID- 7521690
TI  - The active monomeric form of macrophage inflammatory protein-1 alpha interacts
      with high- and low-affinity classes of receptors on human hematopoietic cells.
AB  - Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and its human homologue
      GOS19.1/LD78 are members of the C-C chemokine/intercrine family of secreted
      proteins. They have proinflammatory properties and also inhibit cell cycle
      progression of hematopoietic stem cells. Characterization of MIP-1 alpha
      receptor(s) has been confused because of its reported aggregation to inactive
      forms. Using a defined monomeric form of MIP-1 alpha that is biologically active
      for stem cell inhibition and induction of oxidative metabolism in
      polymorphonuclear cells, we report the detection of high- and low-affinity
      receptor classes on human leukemic CD34+ blast cells, promyelocytic cells,
      monocytes, peripheral blood neutrophils, and T cells. Both high- and low-affinity
      classes are expressed simultaneously in promyelocytes and neutrophils. The
      calculated kd for high-affinity receptors correlates with the concentrations of
      MIP-1 alpha required to induce a biologic effect on stem cells and neutrophils.
      Cross-linking studies show that MIP-1 alpha associates with two cell surface
      proteins with apparent molecular masses of 92 kD and 52 kD. Direct competition
      binding studies combined with studies on the inhibition of stem cells show that
      human and murine MIP-1 alpha have different receptor-binding and biologic
      properties.

PMID- 7521693
TI  - Granulocyte colony-stimulating factor (CSF) but not interleukin-1 (IL-1), IL-3,
      and granulocyte-macrophage CSF protect bone marrow progenitor cells from
      suppression by allosensitized cytotoxic T cells.
AB  - The major immunological reactions after an allogeneic bone marrow transplantation
      (BMT) are graft rejection and graft-versus-host disease (GVHD). GVHD can be
      prevented by T-cell depletion of the allogeneic BM graft, but the beneficial
      effect of T-cell depletion on the incidence of GVHD is counterbalanced by a
      higher incidence of graft failure. One option for the prevention of graft
      rejection after T-cell-depleted BM grafts is the administration of cytokines.
      Before applying cytokines after an allogeneic BMT, we considered it desirable to
      learn whether cytokines would alter the susceptibility of donor BM cells to host
      T cells. An in vitro assay was developed to investigate the role of the cytokines
      interleukin-1 (IL-1), IL-3, granulocyte colony-stimulating factor (G-CSF) and
      granulocyte-macrophage CSF (GM-CSF) on the interaction between allosensitized,
      cytotoxic-T cells (CTLs) and T-cell-depleted BM cells. CTLs primed against the BM
      donor suppressed the formation of colonies consisting of granulocytes and
      macrophages (colony-forming unit GM). Colony formation was not inhibited by CTLs
      sensitized against a third party. Accordingly, the number of colonies scored in
      cocultures with CTLs sensitized to third party antigens were designated as 0%
      inhibition. A 66% inhibition of colony formation was observed for untreated BM
      cells at an effector:target (E:T) ratio of 1:1. Pretreatment of the BM cells with
      the cytokines G-CSF, GM-CSF, IL-1, and IL-3 resulted in a 38% (P = .001), 53%,
      66%, and 68% inhibition of colony formation, respectively, at E:T ratios of 1:1.
      G-CSF reduced the susceptibility of BM cells over a range from 4:1 to 1:16 (E:T
      ratios). GM-CSF had only significant influence at the lower E:T ratios (1:4 and
      1:16). These in vitro data indicate that G-CSF could protect BM cells from
      killing by allosensitized CTLs and suggest that administration of these cytokines
      might potentially reduce the susceptibility of T-cell-depleted allogeneic BM
      grafts to host T-cell-mediated rejection.

PMID- 7521692
TI  - A subset of human CD34+ hematopoietic progenitors express low levels of CD4, the
      high-affinity receptor for human immunodeficiency virus-type 1.
AB  - We investigated the expression of CD4 antigen in normal bone marrow (BM) samples,
      enriched in CD34+ hematopoietic progenitor cells. At flow cytometry, a
      significant fraction (ranging from 25% to 65%) of CD34+ cells also showed low
      levels of CD4 antigen on their surface. The CD4 receptor densities on the surface
      of hematopoietic progenitors was approximately 50% that of peripheral blood
      monocytes and 5% of peripheral blood T lymphocytes. In immunoprecipitation
      experiments, the CD4 antigen expressed by BM hematopoietic progenitors appeared
      to be the same form expressed by mature peripheral blood CD4+ cells and appeared
      to be a potentially functional receptor for human immunodeficiency virus-type 1,
      because it specifically bound recombinant envelope gp120. Moreover, BM samples,
      highly enriched in CD34+ cells, showed the presence of CD4 mRNA at reverse
      transcription-polymerase chain reaction examination. In experiments of complement
      mediated cytotoxicity with Leu3-a+Leu3b anti-CD4 monoclonal antibody, a
      significant reduction in the number of both classes of megakaryocyte (burst
      forming unit-meg [BFU-meg] and colony-forming unit-meg [CFU-meg]) and
      granulocyte/macrophage (CFU-GM) progenitors was observed, whereas erythroid (BFU
      E) progenitors were only slightly affected. Moreover, purified CD4+ BM cells
      obtained by immunomagnetic selection, using high concentrations of Leu3a+Leu3b,
      showed a colony-forming ability of megakaryocyte and granulocyte/macrophage
      progenitors comparable with that of CD4- BM cells. In conclusion, the present
      data show that immature hematopoietic progenitor cells express low levels of CD4,
      the high-affinity receptor of human immunodeficiency virus-type 1.

PMID- 7521691
TI  - Adhesion of committed human hematopoietic progenitors to synthetic peptides from
      the C-terminal heparin-binding domain of fibronectin: cooperation between the
      integrin alpha 4 beta 1 and the CD44 adhesion receptor.
AB  - Close interaction of human hematopoietic progenitors with the bone marrow
      microenvironment is important for the ordered progression of human hematopoiesis.
      Progenitor cell adhesion to stroma has a complex molecular basis, involving
      various cell-extracellular matrix and cell-cell interactions. We have previously
      shown that adhesion of colony-forming cells (CFC) to fibronectin, present in
      stromal extracellular matrix, involves multiple sites, including two heparin
      binding synthetic peptides (FN-C/H I and FN-C/H II) and the alpha 4 beta 1
      integrin-binding peptide CS1. These synthetic peptides are located in close
      proximity in the type III repeat 14 and the immediately adjacent type IIIcs
      region of fibronectin. In the current study, we evaluate receptors expressed by
      CFC responsible for their adhesion to fibronectin. We show that the alpha 4 beta
      1 integrin mediates adhesion to CFC to the peptides FN-C/H I and CS1. Adhesion of
      CFC to fibronectin is also mediated by proteoglycans, because removal of cell
      surface chondroitin-sulfate proteoglycans resulted in decreased adhesion of CFC
      to FN-C/ I and FN-C/H II. The core protein of this proteoglycan was identified by
      immunoprecipitation as a 90-kD member of the CD44 group of adhesion molecules.
      Interestingly, although the proteoglycan core protein failed to adhere to FN-C/H
      II affinity columns, anti-CD44 monoclonal antibodies blocked CFC adhesion to FN
      C/H II, indicating that these monoclonal antibodies may interfere with core
      protein-mediated intracellular signalling. Finally, we show that CD44 and alpha 4
      beta 1 may cooperate in establishing progenitor adhesion, because anti-CD44
      antibodies potentiated the adhesion-inhibitory effects of suboptimal
      concentrations of anti-alpha 4 or anti-beta 1 monoclonal antibodies. These
      results provide a working model for progenitor cell recognition of fibronectin
      (and possibly the marrow micro-environment) in which the coordinated action of
      integrins and cell surface proteoglycans is necessary for cell adhesion. This
      model can now be used to study the complex relationship between progenitor cell
      adhesion and the regulation of their proliferation and differentiation.

PMID- 7521694
TI  - Regulation of endothelial and mesothelial cell function by interleukin-13:
      selective induction of vascular cell adhesion molecule-1 and amplification of
      interleukin-6 production.
AB  - The present study was designed to explore the interaction of interleukin-13 (IL
      13) with vascular endothelial cells (EC). In vitro exposure to IL-13 of human
      umbilical vein EC induced surface expression of vascular cell adhesion molecule-1
      (VCAM-1). At optimal concentrations (10 to 50 ng/mL) and exposure times (24
      hours), IL-13 was a twofold to threefold less effective inducer of VCAM-1 than IL
      1, which was used as reference EC activator. When IL-13 was combined with IL-1,
      an almost additive induction of VCAM-1 was observed. Induction of VCAM-1 by IL-13
      was selective in that E-selectin and intercellular adhesion molecule-1 (ICAM-1)
      were unaffected. IL-13 caused a modest reduction of IL-1 induction of E-selectin
      and ICAM-1. Surface expression of VCAM-1 on IL-13-treated cells was associated
      with mRNA induction (as assessed by Northern analysis and reverse transcriptase
      polymerase chain reaction), with predominance of transcripts encoding the 7 Ig
      domain form of this molecule. In agreement with previous reports, IL-13 inhibited
      cytokine production in human monocytes. In contrast, IL-13 was a weak inducer and
      an amplifier (in concert with IL-1) of IL-6 expression in EC. Mesothelial cells,
      which share properties with EC and regulate the traffic and function of
      leukocytes in serosal cavities, were stimulated to express VCAM-1 and IL-6 by IL
      13. Thus, IL-13 elicits a spectrum of responses in vascular endothelium
      remarkably similar to that of IL-4 and IL-10. Interaction of these cytokines with
      vascular endothelium may play an important role in the induction and expression
      of Th2-dependent responses.

PMID- 7521695
TI  - Expression of axl, a transforming receptor tyrosine kinase, in normal and
      malignant hematopoiesis.
AB  - We previously reported the cloning, and characterization of a receptor tyrosine
      kinase, axl, from two patients with chronic myelogenous leukemia. Herein, we
      describe the expression pattern of axl in normal and malignant hematopoietic
      tissue axl message is detected in normal human bone marrow but not significantly
      in normal blood leukocytes. Cell separation experiments showed that axl is
      expressed in hematopoietic CD34+ progenitor and marrow stromal cells, at low
      levels in peripheral monocytes, but not in lymphocytes or granulocytes.
      Consistent with the normal pattern of axl expression, axl RNA was found
      predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with
      myeloproliferative disorders (acute myeloid leukemia, chronic myeloid leukemia
      (CML) in chronic phase, CML in myeloid blast crisis, and myelodysplasia) showed
      significant axl transcription, as compared with 1 of 45 (2%) lymphoid leukemias
      (chronic lymphocytic leukemia, acute lymphocytic leukemia, and CML in lymphoid
      blast crisis). Treatment of K562 cells with the phorbol ester, 12-O
      tetradecanoylphorbol-13-acetate (TPA), administration of interferon alpha (IFN
      alpha) to normal monocytes, and treatment of U937 cells with TPA and IFN tau
      significantly induced axl expression, supporting a role for this kinase in the
      intracellular signaling of myeloid cells through a variety of biochemical
      pathways. These results suggest that the axl kinase may be operative in normal
      and malignant myeloid biology.

PMID- 7521696
TI  - Transforming growth factor-beta relieves stem cell factor-induced proliferation
      of myelogenous leukemia cells through inhibition of binding of the transcription
      factor NF-jun.
AB  - Transforming growth factor-beta (TGF-beta) is a potent inhibitor of growth factor
      stimulated hematopoiesis in normal and leukemic conditions. Using the factor
      dependent myelogenous leukemia cell lines GF-D8 and Mo7, we show that TGF-beta
      interferes with stem cell factor (SCF)-induced proliferation by downmodulating c
      jun gene expression. The ability of SCF to induce accumulation of c-jun
      transcripts was abolished when TGF-beta was present in culture. Transcriptional
      nuclear run-on assays indicated that TGF-beta relieved the capacity of SCF to
      enhance the transcriptional rate of the c-jun gene. Deletion analysis of the c
      jun promoter furthermore showed that SCF was activating the c-jun promoter via
      the NF-jun transcription factor. Gel mobility shift assays showed that SCF
      increased the binding activity of NF-jun to its recognition site within 5 to 15
      minutes. Binding activity peaked at 1 hour after exposure to SCF and declined to
      starting levels within 4 hours. The ability of SCF to enhance NF-jun binding
      activity was also dose-dependent in the range of 5 to 100 ng/mL. Exposure of GF
      D8 and Mo7 cells to TGF-beta before the addition of SCF antagonized SCF-induced
      NF-jun binding. Moreover, whereas SCF was capable of functionally activating a
      heterologous promoter containing the NF-jun binding site, pretreatment of GF-D8
      cells with TGF-beta abolished transcriptional activation of this heterologous
      promoter. These findings indicate that SCF-mediated activation of c-jun via NF
      jun is crucial for the SCF-inducible proliferative response and is inhibited by
      TGF-beta. In additional experiments, the antisense technique was used. Treatment
      of GF-D8 and Mo7 cells with an antisense oligodeoxyribonucleotide directed
      against the translation initiation site of c-jun abolished the capacity of SCF to
      induce a proliferative response, whereas sense and nonsense oligomers had no
      effect. Taken together, our data indicate that the counteracting modulation of
      the binding activity of NF-jun by SCF and TGF-beta regulates the expression of
      the c-jun gene and thereby the proliferative state of the GF-D8 and Mo7 target.

PMID- 7521697
TI  - Fetal hemoglobin and potassium in isolated transferrin receptor-positive dense
      sickle reticulocytes.
AB  - A subset of sickle cells have an increased density at the reticulocyte stage of
      development, indicating that they are either abnormally dense upon release from
      the bone marrow or become dense quickly in the circulation. These cells are of
      interest because they most likely have severely disrupted cation regulation and a
      short lifespan. Based on the distribution of fetal hemoglobin (HbF) in the
      density fractions of sickle red blood cells (RBCs) and in vitro studies of
      cellular K+ loss, it seems likely that HbF content is an important in vivo
      determinant of dense cell formation. In this study, we tested the hypothesis that
      young, dense cells have low HbF content. Sickle RBCs were first separated into
      light and dense fractions. Reticulocytes were isolated from unfractionated cells
      and from each density fraction with an immunomagnetic technique directed against
      transferrin receptors (TfR) and assayed for the percentage of HbF and K+/Hb
      ratio. TfR+ reticulocytes isolated from unfractionated cells had a much lower HbF
      content when compared with all the unfractionated RBCs. This is most likely
      caused by enrichment of F cells because of a longer circulation life span. Heavy
      TfR+ reticulocytes had a K+/Hb ratio similar to that measured in the entire dense
      population and contained very low levels of HbF, averaging 2.5% of the level in
      all RBCs, 11.7% of the level in all TfR+ reticulocytes, and 4.0% of the level in
      all dense RBCs. These findings suggest that TfR+ dense cells derive predominantly
      from non-F cells. Furthermore, the amount of HbF in the circulating dense cells
      suggests that many of these cells do not derive from the TfR+ dense cells.

PMID- 7521698
TI  - [Percutaneous intraosseous injections in the palliative treatment of bone
      metastases].

PMID- 7521700
TI  - Clearance of valproic acid from cerebrospinal fluid in anesthetized rabbit.
AB  - Clearance of valproic acid from brain tissue is believed to occur via a carrier
      mediated system(s). The present study was designed to determine whether clearance
      was capacity-limited (saturable) and whether it occurred primarily at the choroid
      plexus. Ten rabbits were anesthetized with halothane and surgically prepared for
      ventriculocisternal perfusion. In group 1 (n = 5) valproic acid was added to blue
      dextran-containing mock cerebrospinal fluid (CSF) to achieve concentrations of 5,
      20, 100, and 500 micrograms.ml-1. The mixture was infused through needles in both
      cerebral ventricles. The purpose of this group was to determine whether over a
      large range (100x) of valproic acid concentrations, clearance from CSF was
      capacity limited (saturable). In group 2 (n = 5) valproic acid concentrations
      were 3, 10, and 30 microgram.ml-1 and infusion was into the left cerebral
      ventricle only. The purposes of this group were to determine (a) the magnitude of
      valproic acid clearance for the "clinical" range of valproic acid in CSF (10-30
      micrograms.ml-1), and (b) whether clearance of valproic acid was changed by
      perfusion across a portion of the choroid plexus surface area (group 2) as
      compared with perfusion across the entire choroid plexus surface area (group 1).
      In both groups the percent extraction of valproic acid was calculated from the
      concentration ratio (valproic acid)out/(valproic acid)in corrected for the rate
      of CSF formation. In group 1 the percent extraction of valproic acid was 93 +/-
      2% (mean +/- SD) at 5 micrograms.ml-1 and stabilized within the range of 58-70%
      (individual values) at the higher inflow concentrations of valproic
      acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521699
TI  - Covalent immunochemical membrane labeling of viable cells with K698-T708, a
      simian virus 40 tumor antigen-derived peptide.
AB  - The process of covalent immunochemical linking of viable cell membranes with a
      Simian Virus 40 (SV40) tumor antigen-derived undecapeptide, K(698)PPTPPPEPET(708)
      (KT), is described. The principle applied was the reaction of the lysine residue,
      K 698, of the undecapeptide with the succinimidyl moiety of a heterobifunctional
      linker molecule, N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) or
      sulfosuccinimidyl(4-iodo-acetyl)aminobenzoate (sulfo-SIAB). Thereby, upon release
      of N-hydroxy-succinimide, the rest of the linker molecule reacts covalently with
      the epsilon-NH2 group of lysine. Upon release of pyridyl-2-thion or hydrogen
      iodide, respectively, the second reactive moiety of the linker is then ready to
      form a covalent bond with SH-groups of cell membrane compounds. As a result, KT
      is covalently linked onto the cell membrane by an -SS- or an -S-bond,
      respectively. Binding is prevented by treatment of the candidate cells with
      iodoacetamide, an SH-reactive compound. This artificial cell membrane epitope can
      be demonstrated by surface immunofluorescence and by binding to immunomagnetic
      beads loaded with PAb1605, a KT-specific monoclonal antibody. Quantitation by
      cytofluorimetry shows some 10(4) KT molecules bound per cell, a number that is in
      the range of the number of SV40 tumor antigen molecules of genuine SV40
      transformed mammalian cells.

PMID- 7521701
TI  - Dying at home with AIDS. Primary care perspective.

PMID- 7521702
TI  - cDNA and protein sequences coding for the precursor of phospholipase A2 from
      Taiwan cobra, Naja naja atra.
AB  - The cDNA sequence encoding phospholipase A2 (PLA2) was determined by analysis of
      polymerase-chain-reaction (PCR) product amplified from total cDNA mixture which
      had been constructed from the poly(A)+RNA of venom glands obtained from Taiwan
      cobras. Two oligonucleotide segments corresponding to the 5'- and 3'-noncoding
      regions of sea-snake PLA2 gene were used as primers for PCR-amplified reaction.
      Plasmids of transformed E. coli strain JM109 containing amplified PLA2 cDNA were
      purified and prepared for nucleotide sequencing by dideoxynucleotide chain
      termination method. Sequencing more than five clones containing about 0.5 kb DNA
      inserts revealed two isoforms with complete reading frames of 468 base pairs each
      covering a precursor for phospholipase A2 with a deduced mature protein sequence
      of 119 amino acids and a 27 amino-acid signal peptide. These two enzymes of Group
      I PLA2 differ in six nucleotide residues at the gene level and three amino acids
      along the whole polypeptide chain, each consisting of 14 cysteine residues
      similar to all reported PLA2 of different snake venoms. The signal peptides and
      hydropathy profiles of Group I PLA2 reported here are distinctly different from
      those of Group II PLA2 in viperid snakes.

PMID- 7521703
TI  - Altered expression of alpha-fetoprotein and albumin in early embryonic rat liver
      upon heat shock.
AB  - During rat liver development alpha-fetoprotein (AFP) and albumin (alb) are
      differentially regulated. Alpha-fetoprotein synthesis starts soon after
      fertilization whereas the earliest time albumin could be detected is day 17-18.
      However during normal development trace amounts of albumin mRNA could be detected
      on day 14 or 15. When 12-13 day old embryonic rat liver cells are given heat
      shock at 42 degrees C, there is an enhanced expression of albumin mRNA as well as
      protein. Under heat shock conditions, unlike albumin mRNA, there is specific
      degradation of alphafetoprotein mRNA. Western blot analysis indicated that AFP
      that was already present is not affected by heat shock whereas alpha-fetoprotein
      mRNA is degraded.

PMID- 7521704
TI  - Albumin-like glycoprotein from human fetal tissue.
AB  - Albumin-like glycoprotein (Gp66) with a molecular mass of 66 kDa has been
      isolated from human fetal tissue by size-exclusion, ion-exchange chromatography
      and reverse-phase HPLC. Reactivity of Gp66 with antiserum raised against the
      major protein components fraction of human fetal serum was observed. The N
      terminal 35 amino acid residues of Gp66 were identical to human serum albumin.
      Meanwhile Gp66 differed from albumin by a/ the presence of 3-5 Trp residues
      instead of 1 according to fluorescence and UV-spectra, b/ the glycosylation
      pattern: bi-, tri-, and tetraantennary sialooligosaccharides of a complex type
      were present. Isoelectric focusing revealed 4 isoforms (pI ranging within 4.8 to
      5.1) of Gp66. Gp66 (but not asialo-Gp66) was able to inhibit the cytotoxic effect
      of TNF against the tumor cell line L929. Inhibition of WEHI-3 and L929 tumor
      cells proliferation by Gp66 was similar to that of albumin.

PMID- 7521705
TI  - The fate of GPI-anchored molecules.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins comprise a diverse class of
      membrane molecules. They protect cells from complement-mediated lysis, control
      cell to cell adhesion, activate T cells, and play a role in the etiology of slow
      viral diseases. Despite their functional diversity, GPI-anchored proteins are all
      attached to the plasma membrane by a common glycolipid anchor. We will examine
      one aspect of GPI-anchor metabolism, namely, the processing of the molecule after
      it arrives at the plasma membrane. After biosynthesis and transport to the plasma
      membrane, the GPI-anchored protein can be endocytosed and degraded or cleaved and
      released. The enzymatic machinery controlling the catabolism of GPI-anchored
      molecules at the plasma membrane is likely to play a central role in regulating
      the cell surface expression of these molecules.

PMID- 7521706
TI  - Glycosphingolipid clusters and the sorting of GPI-anchored proteins in epithelial
      cells.
AB  - We studied the role of the association between glycosylphosphatidylinositol (GPI)
      anchored proteins and glycosphingolipid (GSL) clusters in apical targeting using
      gD1-DAF, a GPI-anchored protein that is sorted differentially by three epithelial
      cell lines. Differently from MDCK cells, where both gD1-DAF and glucosylceramide
      (GlcCer) are sorted to the apical membrane, in MDCK Concanavalin A-resistant
      cells (MDCK-ConAr) gD1-DAF was mis-sorted to both surfaces but GlcCer was still
      targeted to the apical surface. In both MDCK and MDCK-ConAr cells, gD1-DAF became
      associated with TX-100 insoluble GSL clusters during transport to the cell
      surface. In contrast to MDCK cells, the Fischer rat thyroid (FRT) cell line
      targeted both gD1-DAF and GlcCer basolaterally. Both MDCK and FRT cells had the
      ability to assemble GSLs into TX-100-insoluble complexes, but, surprisingly, in
      FRT cells, gD1-DAF did not associate with GSLs and, therefore, remained
      completely soluble in TX100. This clustering defect in FRT cells correlated with
      the absence of VIP21/caveolin, a protein localized to both the plasma membrane
      caveolae and the TNG. This suggests that VIP21/caveolin may have an important
      role in recruiting GPI-anchored proteins into GSL complexes, necessary for their
      apical sorting. However, since MDCK-ConAr cells expressed caveolin and clustered
      GPI-anchored proteins normally, yet mis-sorted them, our results also indicate
      that clustering and caveolin are not sufficient for apical targeting and that
      additional factors are required for the accurate apical sorting of GPI-anchored
      proteins.

PMID- 7521709
TI  - A 2.8 Mb YAC contig in 11q12-q13 localizes candidate genes for atopy: Fc epsilon
      RI beta and CD20.
AB  - An important locus for Atopy (familial asthma, hay fever and eczema) has been
      localized to the 11q12-q13 region with the minimum recombination fraction around
      the CD20 gene. We have constructed a 2.8 megabase (Mb) Yeast Artificial
      Chromosome (YAC) contig of the candidate region using 15 STSs. A total of seven
      genes have been mapped within this interval in the order cen-OSBP-TCN1-GIF-Fc
      epsilon RI beta-CD20-CD5-PGA-q(ter) and can be covered by a minimum of eight YAC
      clones. Contig integrity was assayed with fluorescence in-situ hybridization
      (FISH) and the mapping of YAC ends on somatic cell and radiation hybrid panels. A
      long range restriction map of the contig has been constructed to establish the
      order of and distance between loci. Two promising candidates for the atopy locus,
      the beta subunit of the high affinity immunoglobulin E receptor (Fc epsilon RI
      beta) and CD20, a molecule involved in B cell differentiation, have been placed
      within the contig.

PMID- 7521708
TI  - Relationship of interferon synthesis and the resistance of mice infected with
      street rabies virus.
AB  - Genetically homogeneous and heterogeneous mouse populations were tested for
      resistance to experimental street rabies virus infection and their ability to
      synthesize interferon (IFN) during the infection. The genetically heterogenous HI
      mouse population was highly resistant (12% mortality), and the genetically
      homogeneous BALB/c and C3H mice as well as the genetically heterogeneous Sw and
      LI mouse populations were susceptible (60 to 71% mortality). The genetically
      homogeneous A/J mice were highly susceptible (85% mortality) to experimental
      street rabies infection. The ability of these mice to synthesize IFN as measured
      in serum 4 days after the infection was directly related to the degree of
      resistance, with the highly resistant HI mice showing large amounts of IFN (850
      U/ml), and the susceptible mice showing low amounts of IFN (50 to 280 U/ml). IFN
      induced within the central nervous system and measured in brain homogenates
      during infection was not correlated with resistance. The present data suggest
      that high levels of IFN occurring in serum early during infection with street
      rabies virus contribute to the resistance of these mice.

PMID- 7521707
TI  - Binding of GPI-PLD-treated DAF to the surface of Schistosoma mansoni
      schistosomula.
AB  - Decay accelerating factor (DAF,CD55) is a 70-kDa glycosylphosphatidylinositol
      (GPI)-anchored protein that protects human erythrocytes (HuE) from complement
      mediated damage by regulation of the C3-convertase. Purified human DAF can be
      incorporated into sheep red blood cell (SRBC) membrane and confer complement
      resistance on these DAF-deficient cells. Here, we demonstrate that normal HuE or
      their stroma (HuES) incubated at 37 degrees C for 24 h release soluble DAF in a
      biologically active form into the culture medium. This soluble DAF neither
      inserts into SRBC plasma membranes nor presents the cross-reacting determinant
      (CRD) characteristic of the hydrolysis by phosphatidylinositol-specific
      phospholipases C (PI-PLC) but binds to schistosomula of S. mansoni protecting
      them from antibody-mediated complement-dependent damage. To study the binding of
      DAF to schistosomula in vitro, we have used purified human DAF labeled with
      125I(125I-DAF), intact or treated with either PI-PLC or GPI-PLD
      (glycosylphosphatidylinositol-specific phospholipase D). We have found that GPI
      PLD-treated DAF binds to the surface of parasites more readily than intact or PI
      PLC-treated DAF. Immunoprecipitation of the samples with a monoclonal anti-human
      DAF antibody (IA10) revealed that schistosomula incubated with GPI-PLD-treated
      125I-DAF emit a stronger signal than their counterparts. This result indicates
      that the surface of schistosomula is capable of acquiring GPI-PLD-treated DAF
      more effectively than intact or PI-PLC-treated molecules.

PMID- 7521710
TI  - Sensitivity of single-strand conformation polymorphism and heteroduplex method
      for mutation detection in the cystic fibrosis gene.
AB  - The gene responsible for cystic fibrosis (CF) contains 27 coding exons and more
      than 300 independent mutations have been identified. An efficient and optimized
      strategy is required to identify additional mutations and/or to screen patient
      samples for the presence of known mutations. We have tested several different
      conditions for performing single-stranded conformation polymorphism (SSCP)
      analysis in order to determine the efficiency of the method and to identify the
      optimum conditions for mutation detection. Each exon and corresponding exon
      boundaries were amplified. A panel of 134 known CF mutations were used to test
      the efficiency of detection of mutations. The SSCP conditions were varied by
      altering the percentage and cross-linking of the acrylamide, employing MDE (an
      acrylamide substitute), and by adding sucrose and glycerol. The presence of
      heteroduplexes could be detected on most gels and in some cases contributed to
      the ability to distinguish certain mutations. Each analysis condition detected 75
      98% of the mutations, and all of the mutations could be detected by at least one
      condition. Therefore, an optimized SSCP analysis can be used to efficiently
      screen for mutations in a large gene.

PMID- 7521711
TI  - Molecular characterization of the major outer-membrane protein OprF from plant
      root-colonizing Pseudomonas fluorescens.
AB  - N-terminal sequence analysis of peptides generated by proteolytic treatment of
      the Pseudomonas fluorescens OE 28.3 major outer-membrane protein OprF, embedded
      in outer membranes or present in whole cells, indicated a surface-exposed
      location for the proline-rich region of the protein. This region is absent from
      the P. aeruginosa and P. syringae OprFs. Evidence was obtained for the presence
      of additional exposed but less accessible regions in the carboxy half of OprF.
      Four OprF-specific monoclonal antibodies were all directed to the C-terminal part
      of the protein but did not recognize a surface-exposed epitope as shown by flow
      cytometry. Our data support the model previously proposed for P. aeruginosa OprF
      in which the entire protein is embedded in the outer membrane, unlike the
      topology proposed for the major outer-membrane protein from Escherichia coli,
      OmpA, whose carboxy half resides in the periplasmic space. For six other P.
      fluorescens strains producing OprF proteins with different isoelectric points,
      the primary structure was determined by sequence analysis of the PCR-amplified
      oprF genes. The proline-rich domain represented the most conserved region of the
      different P. fluorescens OprFs. Based on the sequence of its oprF gene, it was
      shown that the mushroom pathogen P. tolaasii is quite closely related to P.
      fluorescens. Comparative sequence analysis further showed that the carboxy half
      of OprF contains a sequence motif that is well conserved in the enterobacterial
      OmpA proteins but is also present in a number of other outer-membrane proteins,
      including peptidoglycan-associated lipoproteins.

PMID- 7521712
TI  - Influence of salmeterol, a long-acting beta 2-adrenoceptor agonist, on IgE
      mediated histamine release from human basophils.
AB  - Salmeterol, a long-acting beta 2-adrenoceptor agonist, prevents early and late
      asthmatic responses in atopic asthmatics and inhibits the release of inflammatory
      mediators from various cells and tissues. We investigated the effect of
      salmeterol on in vitro basophil histamine release (BHR). Washed basophil
      leukocytes from allergic (n = 6) and nonallergic subjects (n = 18) were
      preincubated for 10 min with different concentrations of salmeterol prior to
      stimulation with antigens (Ag) and anti-IgE for 45 min. BHR was detected by an
      automated fluorometric assay. If control BHR (without inhibition) reached > or =
      30% of the total histamine content, maximal % inhibition (Imax, mean +/- SEM) and
      the concentration of salmeterol causing 30% inhibition (IC30, geometric mean)
      were calculated. At concentrations of between 1 and 100 microM salmeterol,
      concentration-dependent inhibition of release was found for Ag- and anti-IgE
      mediated BHR. The Imax of anti-IgE-mediated BHR reached 46 +/- 16% at 30 microM
      salmeterol. IC30 values were 12 microM for Ag- and 8 microM for anti-IgE-induced
      BHR. Higher concentrations of salmeterol induced BHR in all subjects (n = 24, 100
      microM: 28 +/- 5% BHR), overlapping the inhibitory effect on BHR. Kinetic studies
      using 30 microM salmeterol (n = 10) showed > 30% inhibition with short
      preincubation periods (< 10 s). Salbutamol, an older, widely used beta 2
      adrenoceptor agonist, had no effect on IgE-mediated BHR (n = 8). We conclude that
      salmeterol significantly inhibits IgE-mediated histamine release from human
      leukocytes in the micromolar range.

PMID- 7521713
TI  - The efficacy of choline magnesium trisalicylate (CMT) in the management of
      metastatic bone pain: a pilot study.
AB  - Twenty-six patients with painful, bony metastases were recruited into a
      randomized, double-blind, single dose, two-treatment, three-part crossover study
      of choline magnesium trisalicylate (CMT) and placebo. Assessments were made prior
      to and at one, two, three and four hours after dosing. Bone pain caused by
      metastatic cancer was significantly relieved one hour after the administration of
      1500 mg CMT (p = 0.04). At all four time points the pain was less than baseline
      with CMT and at three time points greater than baseline with placebo but these
      results did not reach statistical significance. The summed pain intensity
      difference for patients was greater with CMT than with placebo, but this also did
      not reach significance. The incidence of volunteered side-effects was similar for
      both treatments. The results suggest that a nonacetylating, nonsteroidal anti
      inflammatory drug may have a role complementary to that of an opioid in the
      management of metastatic bone pain.

PMID- 7521715
TI  - Successful use of methadone in nociceptive cancer pain unresponsive to morphine.
AB  - Morphine is the mainstay of pain control in cancer patients. We describe three
      patients in whom adequate analgesia was not obtained with morphine, and discuss
      the role of morphine metabolites and the use of methadone as an alternative
      strong opioid analgesic.

PMID- 7521717
TI  - Anticipatory grief: a theoretical challenge.
AB  - The theories of loss and grief described by Freud and Bowlby have provided
      considerable interest in anticipatory grief. Anticipatory grief is assumed to be
      akin to post-death grief, but commencing prior to the loss of the loved one.
      'Grief work' completed during the anticipatory period is purported to mitigate
      against abnormal grief reactions after death and enhance adjustment to loss.
      Research conducted to investigate the link between anticipatory grief and
      postbereavement adjustment has not, however, yielded conclusive findings. It is
      argued that the intellectual vision of researchers has been obscured by the
      traditional view of grief leading to conceptual confusion in the theoretical
      literature and equivocal findings of the empirical investigations. The limited
      view of the 'death event' as the only loss incurred fails to consider the past,
      present and future losses that may occur as a result of terminal disease. The
      physiological, psychological, interpersonal and sociocultural factors evident in
      the terminal situation serve to highlight the existence of many previously
      unconsidered variables which may determine the anticipatory grief experience.
      Until the influence of these determining variables is acknowledged and
      researchers learn to look beyond the parameters of the traditional models of
      grief, the costs and/or benefits of the anticipatory period will remain largely
      undefined. A good starting point may be the adoption of the alternative label,
      'terminal response'.

PMID- 7521714
TI  - Monitoring drug use in palliative care.
AB  - A computerized system for monitoring drug use which makes use of the British
      National Formulary (BNF) drug categories and a departmental formulary (DF) has
      been developed. Data entry takes less than one week of secretarial time per
      annum. Details of drug use in 385 patients three weeks after referral to a
      National Health Service palliative care unit over five years form the basis of
      this report. The median number of drugs per patient was five, with a maximum of
      11; 97% of the drugs were from the DF. Analgesics were the commonest category of
      drugs used. The 10 most commonly used drugs included three analgesics (morphine,
      co-proxamol, flurbiprofen), two laxatives (co-danthrusate, lactulose),
      dexamethasone, metoclopramide, ranitidine, temazepam and amitriptyline/dothiepin.
      Seventeen per cent of patients received two preparations from the same second
      level BNF category (analgesics excluded). The concurrence was questionable in
      about half of these, and mostly related to the use of laxatives or to hypnotics
      and anxiolytics. Several unexpected inclusions in the top 10 drugs illustrate the
      need for quantification rather than pontification about drug use in palliative
      care. Examination of duplicate prescribing provides a forum for examining ways of
      simplifying drug regimens.

PMID- 7521716
TI  - Tube feeding in palliative care: benefits and problems.
AB  - Percutaneous endoscopic gastrostomy techniques are becoming more widely available
      and will be considered increasingly for patients with head and neck or upper
      gastrointestinal malignancies, and for neurological dysphagia, as occurs in motor
      neurone disease. This case history illustrates some of the practical and ethical
      issues raised by their use.

PMID- 7521718
TI  - Symptom control: the problem areas.

PMID- 7521719
TI  - Octreotide in palliative medicine.

PMID- 7521720
TI  - Impact of a palliative care unit on morphine consumption in Gran Canaria (Spain)

PMID- 7521721
TI  - At the crossroads: which direction for the hospices?

PMID- 7521722
TI  - Subcutaneous infusions--a medical last rite.

PMID- 7521723
TI  - Radiotherapy for painful bone metastases.
AB  - Bone metastases are a frequent cause of morbidity in patients with malignant
      disease. Pain is the commonest symptom; it can be treated successfully in the
      majority of patients by local external beam irradiation. Controversy exists over
      which regimen should be used, with a single dose necessitating only one treatment
      visit to the radiotherapy department, or a fractionated course requiring several
      visits. Many radiotherapists continue to use fractionated regimens despite the
      current evidence that single fractions are as effective. Many reasons exist for
      this, including departmental policy and training, fears of recurrence, problems
      with retreatment of previously treated areas, fears of increased early and late
      morbidity, and attempts at promoting recalcification. The majority of these
      reasons are theoretical and have yet to be substantiated. In many patients,
      symptomatic bone metastases are widespread, and hemibody irradiation, although
      more toxic, should be considered in order to avoid the need for repeated courses
      of local treatment.

PMID- 7521725
TI  - Some issues in non-convulsive status epilepticus in children and adolescents with
      learning difficulties.
AB  - Individuals with learning difficulties commonly suffer from concomitant
      conditions; epilepsies constitute up to 35%. The prevalence of epileptic
      syndromes in learning disabled people is less well documented. Non-convulsive
      status epilepticus (NCSE) occurs with many epileptic syndromes. It can present
      with insidious or paroxysmal change of neurovegetative, behavioural, cognitive or
      affective symptoms which can mistakenly be attributed to other causes. NCSE of
      generalized epilepsy syndromes can show localizing features and NCSE of
      localization-related epilepsy can show generalized epileptiform discharge
      patterns. We reviewed 14 residents' (< 20 years, all learning disabled) EEG
      recordings in inter-ictal stages and in NCSE and conclude that the current
      nosological grouping of NCSE does not ensure appropriate categorization in a
      significant number of cases. We developed a revised NCSE classification: (I)
      Generalized epileptic syndromes: (a) with no evidence of lateralization inter
      ictally or in NCSE; (b) with evidence of lateralization in NCSE only. (II)
      Localization-related epileptic syndromes: (a) with evidence of
      lateralization/focal activity in NCSE; (b) with evidence of generalized EEG
      patterns when in NCSE only; (c) with transient forms: same individual shows
      generalized and lateralized/focal NCSE activity in different EEGs. We suggest our
      system be tested in larger studies for its sensitivity, reliability and validity.

PMID- 7521724
TI  - T-cell receptor repertoire in colorectal adenocarcinoma patients with hepatic
      metastases and its changes induced by preoperative adjuvant interleukin-2
      therapy.
AB  - The liver is the primary site for colorectal metastases and hepatic resection
      often fails to cure these patients. Little is known about T-cell immune response
      in these patients or its changes after interleukin-2 (IL-2) infusion. Using
      polymerase chain reaction methodology, we investigated T-cell receptor (TCR) V
      alpha and V beta gene segment subfamily usage in tumor, hepatic tissue, and blood
      of six patients undergoing hepatic resection and, in addition, in six patients
      receiving preoperative adjuvant IL-2 therapy (randomized phase I trial). The
      objectives were (a) to analyze the TCR repertoire in patients undergoing hepatic
      resection (without IL-2), (b) to analyze the TCR repertoire in patients
      undergoing hepatic resection after IL-2 therapy, (c) to analyze the effects of
      preoperative IL-2 infusion on the tumor-infiltrating lymphocyte (TIL) TCR
      repertoire by comparing TCR V gene segment usage in IL-2-treated versus
      nontreated patients, and (d) to analyze the effect of IL-2 infusion on the
      peripheral blood mononuclear cell (PBMC) TCR repertoire by comparing TCR V gene
      segment expression in pre- versus posttreatment PBMC of IL-2-treated patients.
      With regard to the first objective, we observed an unrestricted use of V alpha
      and V beta gene segment subfamily specificities in tumor hepatic tissue and blood
      of patients undergoing hepatic resection. In addition, we found that some V alpha
      and V beta specificities were overexpressed in tumor compared with hepatic tissue
      and blood, suggesting that the corresponding T-cell subpopulations were expanded
      at the tumor site. In IL-2-treated patients, in whom the tumor and liver were
      heavily infiltrated by T lymphocytes, the TIL TCR repertoire was also highly
      diverse and roughly similar to that detected in hepatic tissue and blood, except
      for a few overexpressions. To analyze the effect of IL-2 on TIL, we next compared
      the data obtained in IL-2-treated versus nontreated patients. No significant
      difference between the two groups was observed. Finally, no major changes in the
      PBMC TCR repertoire were found after IL-2 infusion. Further studies are needed to
      identify discrete T-cell subpopulations in these patients that may participate in
      either tumor immune surveillance or active immunotherapy mechanisms triggered by
      systemic IL-2 infusion.

PMID- 7521726
TI  - Conservation of the tandem arrangement of alpha 1-microglobulin/bikunin mRNA:
      cloning of a cDNA from plaice (Pleuronectes platessa).
AB  - alpha 1-Microglobulin and bikunin are both plasma proteins which are synthesized
      in mammalian liver from a common mRNA with tandemly arranged coding sequences.
      Here, we report a piscine homologue of mammalian alpha 1-microglobulin/bikunin
      mRNA which was serendipitously isolated from a plaice (Pleuronectes platessa)
      liver cDNA library. The piscine cDNA recognized an approximately 1300 nucleotide
      mRNA on Northern blots of plaice liver RNA and, to a lesser extent, on blots of
      kidney and whole blood RNA. The deduced amino acid sequence displayed very
      similar tandemly arranged and homologous sequences for alpha 1-microglobulin and
      bikunin to those found in the corresponding mammalian cDNAs (35-38% amino acid
      identity for alpha 1-microglobulin and 45-50% for bikunin). Southern blots of
      plaice genomic DNA demonstrate that there are probably no closely related genes
      in addition to the gene for this cDNA. Taken together, these results suggest that
      the structure of the alpha 1-microglobulin/bikunin mRNA and gene is conserved in
      fish and mammals, implying an important common function for the tandem expression
      of these proteins.

PMID- 7521727
TI  - Biochemical characterization of bovine alpha-fetoprotein and comparison with
      human alpha-fetoprotein.
AB  - This study compares the molecular, charge and lectin microheterogeneity of bovine
      alpha-fetoprotein (bAFP) with human (h) AFP. Molecular weights of bAFP (81 kDa)
      and hAFP (69 kDa) were detected by Western immunoblotting. Marked crossreactivity
      was found between bAFP and hAFP by Western immunoblotting but no crossreactivity
      was noticed by radioimmunoassays. At least seven charge isoforms of bAFP and
      three isoforms of hAFP were consistently detected by chromatofocusing in a
      mixture of fetal bovine serum (FBS) and human cord blood (hCB), while only three
      isoforms of bAFP and hAFP were detected in a mixture of bovine (bAF) and human
      amniotic fluid (hAF). Using concanavalin A (Con A) chromatography, 50% of bAFP
      was Con A reactive and 50% non-reactive, while more than 98% of hAFP was Con A
      reactive in a mixture of FBS and hCB. However, in AFs, 72% of bAFP was Con A
      reactive, while 89% of hAFP was Con A reactive. These data indicate that marked
      differences exist in both the charge and lectin microheterogeneity of bovine and
      human AFP.

PMID- 7521728
TI  - Developmental changes in serum IGF-1 and IGFBP levels and liver IGFBP-3 mRNA
      expression in intrauterine growth-retarded and control swine.
AB  - The 29 M(r) x 10(-3) IGFBP was significantly elevated (P < 0.01) in IUGR piglets
      at 90 days fetally and at birth. Developmentally, 29 M(r) x 10(-3) IGFBP levels
      were higher fetally and at birth than at 21 and 49 days of age (P < 0.05). At 90
      days fetally, hepatic IGFBP-3 mRNA levels were very high, while circulating
      levels of IGFBP-3 were extremely low whereas postnatally, hepatic IGFBP-3 mRNA
      and serum IGFBP-3 levels were parallel. This study provides new information
      concerning the developmental expression of IGFBP-3 and the relationship between
      serum levels of the 29 M(r) x 10(-3) IGFBP and IUGR in swine.

PMID- 7521730
TI  - Bronchoscopic treatment of lung tumors.
AB  - Several bronchoscopic techniques for the treatment of patients with
      tracheobronchial pathology have become available during the last decade.
      Technical development and additional instruments have provided the bronchoscopist
      with several alternatives for bronchoscopic therapeutic interventions. The
      majority of patients with malignant tracheobronchial neoplasm have a dismal
      prognosis. Palliation is the main aim of the treatment. However, in patients with
      an early-stage tumor, bronchoscopic treatment may have a curative potential.
      Resectability, after tumor reduction by a bronchoscopic treatment, may be
      improved. This article discusses various bronchoscopic techniques, the advantages
      and disadvantages of each method and the possible benefit which can be derived
      from such a treatment.

PMID- 7521731
TI  - Platinum-based chemotherapy for inoperable non-small cell lung cancer: a real
      therapeutic progress?

PMID- 7521729
TI  - Serotransferrin, ovotransferrin and metallothionein levels during an immune
      response in chickens.
AB  - Extracellular iron-binding proteins function in iron transport, iron scavenging
      and bactericidal activity. To determine whether the levels of chicken iron
      binding proteins are altered during an immune challenge, young broiler chicks and
      40-week-old hens were injected with lipopolysaccharide (LPS). Serum transferrin
      and liver mRNA for serum transferrin increased at 24 hr after injection.
      Increased levels of serum transferrin and hepatic mRNA for serum transferrin
      define chicken serum transferrin as an acute-phase protein. Magnum mRNA for
      ovotransferrin decreased 24 hr after the immune challenge in hens. Hens had also
      stopped ovulating, suggesting that synthesis of all egg proteins was decreased.

PMID- 7521732
TI  - Japanese doctors' preferred treatment choices for their hypothetical non-small
      cell lung cancer: how they would wish to be treated. National Chest Hospital
      Study Group for Lung Cancer.
AB  - We conducted a trial to clarify what Japanese clinical doctors think about the
      present status of therapy for non-small cell lung cancer, as well as to clarify
      which problems are still unresolved. One-hundred five Japanese doctors who treat
      lung cancer patients were asked how they would choose to be treated, if they
      suffered from non-small cell lung cancer. Six scenarios were presented and the
      doctors had to choose one treatment method for each of the six scenarios.
      Adjuvant chemotherapy or radiotherapy after complete resection, increase with
      progression of the pathological stage. Ninety-three per cent of Japanese doctors
      wanted surgery, even if mediastinal lymph node metastases were present. In the
      scenario of only one distant metastasis to the brain, 44% of doctors wanted
      surgery while 39% wanted chemotherapy and/or radiotherapy. In the scenario of
      multiple bone metastases, 33% wanted chemotherapy, 77% did not. It was concluded
      therefore that Japanese doctors choose surgery as the number one treatment
      modality when all lesions are considered resectable.

PMID- 7521733
TI  - Substance P regulation of glutamate and cystine transport in human astrocytoma
      cells.
AB  - UC11 human astrocytoma cells transported glutamate by at least two distinct
      systems which appeared to be very similar to the Na(+)-dependent XAG- system
      (glutamate and aspartate are preferred substrates) and the Na(+)-independent xc-
      system (glutamate and cystine are preferred substrates) described in other cells,
      including primary cultures of rat astrocytes. The xc- system accounted for about
      80% of the total glutamate influx. In a Na(+)-free buffer, the average Km and
      Vmax values for glutamate influx in UC11 cells were 167 +/- 15 microM and 0.82 +/
      0.04 nmoles/min/mg protein. Substance P, acting via an NK1 receptor, caused half
      maximal inhibition of glutamate and cystine transport at a peptide concentration
      of approximately 3 nM. Maximal inhibition was usually in the range of 60-80% and
      was noncompetitive in nature. Substance P also induced a significant increase in
      the release of endogenous glutamate. These effects of Substance P may be of
      pathophysiological significance in the CNS: first, a combination of inhibition of
      glutamate influx and stimulation of glutamate efflux from astrocytes is
      potentially toxic with respect to nearby neurons; second, an inhibition of
      cystine influx could result in a depletion of intracellular glutathione,
      resulting in increased sensitivity to oxidative stress.

PMID- 7521734
TI  - The transmembrane region of the nicotinic acetylcholine receptor: is it an all
      helix bundle?
AB  - The nicotinic acetylcholine receptor is the best characterised member of the
      Ligand-Gated-Ion-Channel family of receptors. In spite of a wealth of data from
      molecular cloning studies these receptors have so far eluded all attempts at
      crystallisation; quantitative structural data are few and are at relatively low
      resolution. The widely accepted current model for the topology of the receptors
      is that of a pentameric cylindrical bundle that spans the membrane. The
      disposition of the transmembrane region of the individual subunits is based on
      hydropathy profiles calculated from sequence data which are interpreted as
      indicating a common structural motif of four antiparallel alpha-helices, M1 to
      M4. Until very recently this model has been unquestioned even though there are
      few direct experimental data to support it. We have constructed models of this
      key functional region for the nicotinic acetylcholine receptor, building out from
      the ion-channel. The model of the basic ion-channel comprises a five helical M2
      bundle with a left-handed twist. The remainder of the region (M1, M3, M4) was
      homology modelled, together with M2, as a four helix antiparallel bundle per
      subunit, using the crystal structure of myohaemerythrin as a template. The models
      strongly suggest that the four helix bundle model is inappropriate and that
      recent suggestions of a mixed motif of helix and sheet may better accommodate the
      existing data.

PMID- 7521735
TI  - Crystal structures of peptide complexes of the amino-terminal SH2 domain of the
      Syp tyrosine phosphatase.
AB  - BACKGROUND: Src homology 2 (SH2) domains bind to phosphotyrosine residues in a
      sequence-specific manner, and thereby couple tyrosine phosphorylation to changes
      in the localization or catalytic activity of signal transducing molecules.
      Current understanding of SH2 specificity is based on the structures of SH2
      peptide complexes of the closely-related Src and Lck tyrosine kinases. The
      tyrosine phosphatase Syp contains two SH2 domains that are relatively divergent
      from those of the tyrosine kinases, with distinct target specificities, and is
      thus well suited for structural studies aimed at extending our understanding of
      SH2 specificity. RESULTS: Crystal structures of the amino-terminal SH2 domain of
      Syp in separate complexes with two high-affinity peptides, in complex with a non
      specific peptide and in the uncomplexed form have been determined at between 2 A
      and 3 A resolution. The structure of the SH2 domain and the mode of high-affinity
      peptide binding is essentially similar to that seen in the Src and Lck
      structures. However, the binding interface is more extensive in Syp. CONCLUSIONS:
      Most SH2 targets have hydrophobic residues at the third position following the
      phosphotyrosine, and the Syp structure confirms that the peptide is anchored to
      the SH2 surface by this residue and by the phosphotyrosine. In addition, the Syp
      structure has revealed that sequence specificity can extend across the five
      residues following the phosphotyrosine, and has shown how the SH2 domain's
      surface topography can be altered with resulting changes in specificity, while
      conserving the structure of the central core of the domain.

PMID- 7521736
TI  - Inhibition of PHA induced mononuclear cell proliferation by FK506 in combination
      with cyclosporine, methylprednisolone, 6-mercaptopurine and mycophenolic acid.
AB  - In vitro inhibition of human peripheral blood mononuclear cell (PBMC)
      proliferation by immunosuppressive drugs has been shown to correlate with
      clinical outcomes in kidney transplant patients. The aim of our study was to
      analyse the degree of variability of in vitro interactions of FK506 (FK) with
      combinations of cyclosporin A (CyA), methylprednisolone (MP), 6-mercaptopurine
      (6ME), and mycophenolic acid (MPA) using phytohaemagglutinin (PHA) stimulated
      PBMCs. Our hypotheses were: that a wide range of interindividual variation would
      be detected; and that certain combinations of drugs would have a synergistic
      inhibitory effect on PHA stimulated PBMCs. Cells were cultured in supplemented
      RPMI 1640 for 65 hours at 37 degrees C in humidified 5% CO2 - 95% air and
      proliferative responses measured by 3H-thymidine incorporation over a further 24
      hours. Inhibition of PBMC proliferation was assessed over 10 FK concentrations
      ranging from 1 x 10(-8) to 10 micrograms/ml using both volunteer controls (n =
      51) and dialysis patients (n = 23). A wide range of interindividual variability
      of FK inhibition occurred throughout the range of FK concentrations tested,
      becoming less variable at the higher concentrations. The interactions of FK with
      CyA, MP, 6ME and MPA were assessed using PBMCs from 12 volunteer controls. For FK
      at 1 x 10(-8) micrograms/ml; CyA, MP, 6ME and MPA were used at 0.01 microgram/ml.
      For FK at 1 x 10(-7) micrograms/ml; CyA, MP, 6ME and MPA were used at 0.1
      microgram/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521737
TI  - Adhesion molecule expression (ICAM-1, VCAM-1, E-selectin and PECAM) in human
      kidney allografts.
AB  - Expression of the cellular adhesion molecules ICAM-1, VCAM-1, E-selectin and
      PECAM in human kidney allografts was assessed by immunoperoxidase labelling of
      cryostat sections. Biopsies from 10 kidneys immediately prior to transplantation
      and 58 biopsies from 51 kidney transplants with graft dysfunction were studied.
      Allograft dysfunction was due to acute tubular necrosis (n = 5), acute rejection
      (n = 30), cyclosporin A (CyA) nephrotoxicity (n = 6), acute pyelonephritis (n =
      3), recurrent glomerulonephritis (n = 4) and chronic rejection (n = 10). There
      was variability in the distribution of ICAM-1, VCAM-1 and E-selectin expression
      in pretransplant kidneys but the principal observation was a marked increase in
      the expression of ICAM-1 and VCAM-1 by the renal vasculature and the proximal
      tubules during acute rejection. By contrast, grafts with dysfunction not
      attributed to rejection showed a pattern of ICAM-1 and VCAM-1 expression similar
      to that observed prior to transplantation. E-selectin was expressed only weakly
      by occasional intertubular capillaries during acute rejection but the three
      grafts with pyelonephritis displayed strong expression of E-selectin on
      intertubular capillaries. There was no change in the pattern of PECAM expression
      following transplantation. The induction of ICAM-1 and VCAM-1 during rejection
      may contribute to the recruitment of mononuclear cells and render endothelial and
      tubular renal cells more susceptible to cell-mediated injury.

PMID- 7521738
TI  - Effects of combined administration of FK 506 and the purine biosynthesis
      inhibitors mizoribine or mycophenolic acid on lymphocyte DNA synthesis and T cell
      activation molecule expression in human mixed lymphocyte cultures.
AB  - Our objective was to obtain new information on the in vitro antilymphocytic
      action of the cytokine synthesis inhibitor FK 506 and the purine biosynthesis
      inhibitors mycophenolic acid (MPA; the active moiety of RS61443) and mizoribine
      (MZB) when used alone or in combination. When added at the initiation of six-day
      human mixed lymphocyte cultures (MLC), FK 506, MPA or MZB exhibited dose
      dependent inhibition of T-lymphocyte DNA synthesis. FK 506, however, was 100-fold
      more potent than MPA, and 10,000-fold more potent than MZB. Combination of FK 506
      with either MPA or MZB, each at suboptional concentrations, produced no more than
      additive inhibitory effects on 3H thymidine incorporation. Two-colour flow
      cytometric analysis of lymphocytes revealed that none of the drugs affected cell
      surface activation molecule expression (CD25 = IL-2R 55 kD alpha-chain, HLA-DR or
      CD71 = transferrin receptor [TR]) on allostimulated CD4+ or CD8+ cells harvested
      at three days of culture. By day six, however, all three agents, at levels which
      markedly inhibited proliferation, suppressed the expression of activation markers
      on both CD4+ and CD8+ cells. Also at day six, inhibition of activation molecule
      expression on CD4+ cells was achieved with the combination of FK 506 and either
      MPA or MZB at concentrations which, on their own, were ineffective. These data
      provide new, additional information on the in vitro antilymphocytic action of FK
      506, MPA and MZB when used alone and in combination.

PMID- 7521740
TI  - Identification of alpha-galactosyl and other carbohydrate epitopes that are bound
      by human anti-pig antibodies: relevance to discordant xenografting in man.
AB  - Human anti-pig antibodies were obtained by perfusing pig hearts (n = 4) and
      kidneys (n = 8) with human AB or O plasma followed by elution with 3 M NaSCN. The
      antibodies were screened against a panel of 132 synthetic carbohydrates
      conjugated to bovine serum albumin using an enzyme-linked immunoassay. An anti
      immunoglobulin antibody was also used to detect immunoglobulin deposits on pig
      tissues. Four carbohydrate molecules with a terminal alpha-galactose residue
      bound all but one of the human anti-pig kidney antibodies and most of the anti
      pig heart antibodies. These were: (i) alpha Gal(1-->3)beta Gal(1-->4)beta GlcNac
      (linear B type 2); (ii) alpha Gal(1-->3)beta Gal(1-->4)beta Glc (linear B type
      6); (iii) alpha Gal(1-->3)beta Gal(B disaccharide); and (iv) alpha Gal(alpha-D
      galactose). Immunoglobulin deposition was documented post-plasma perfusion in all
      pig hearts and particularly strongly in all pig kidneys. These results suggest
      that human anti-pig antibodies are mainly directed against alpha-galactosyl
      structures. Extracorporeal immunoadsorption of human plasma through columns of
      the specific synthetic carbohydrate(s) might lead to depletion of anti-pig
      antibodies and allow discordant xenografting in man. Alternatively, the infusion
      of the specific carbohydrate(s) for a period of several days might result in
      neutralization of the anti-pig antibodies and allow accommodation to take place.

PMID- 7521741
TI  - Intragraft cytokine mRNA levels in human liver allograft rejection analysed by
      reverse transcription and semiquantitative polymerase chain reaction
      amplification.
AB  - Cytokine gene expression was analysed by reverse transcriptase-polymerase chain
      reaction (RT-PCR) amplification of RNA from 27 human liver allograft specimens
      diagnosed as acute (n = 19) or chronic (n = 8) rejection and from 12 normal human
      livers. In initial screening experiments, mRNA for cytokines interleukin (IL)-1
      beta, IL-6, IL-10 and gamma-interferon (IFN-gamma) was expressed in all normal
      livers and almost all allograft specimens tested. IL-2 mRNA was expressed at
      barely detectable levels in four of 12 normal livers screened and in 20 of 26
      liver allograft specimens with rejection. This constitutive expression of
      cytokine mRNA required semiquantitative PCR analysis to differentiate levels of
      cytokine mRNA expression between specimens. Titration of cDNA prior to PCR
      amplification was initially used and showed significantly more IL-2 (p = 0.02)
      and IFN-gamma (p = 0.03) in acute rejection compared to normal liver. There was
      also significantly less IL-10 in chronic rejection compared to acute rejection (p
      = 0.02) or normal liver (p = 0.01) and less IL-6 in acute rejection compared to
      chronically rejecting liver (p = 0.05). IL-1 beta (p = 0.04) and IL-6 (p = 0.01)
      were reduced in acute rejection compared to normal liver. The slight increase of
      IL-2 in acute rejection and the slight decrease of IL-10 in chronic rejection was
      confirmed by a second semiquantitative analysis which involved removal of
      aliquots of PCR reaction at successive cycles followed by dot-blotting and
      hybridization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521742
TI  - Organ-specific unresponsiveness induced by intrathymic injection of donor bone
      marrow cells and a short course of immunosuppression in the rat heart
      transplantation model.
AB  - Donor- and organ-specific unresponsiveness to Brown Norway (BN) heart allografts
      was achieved in Lewis (LEW) rats by giving intrathymic donor bone marrow cells
      (ITBMC) and immunosuppression at the time of transplantation. Antilymphocyte
      serum (ALS) (1 ml, days 0, 2, 4) extended graft survival to a median survival
      time (MST) of 29.5 days (n = 6), while ALS + ITBMC extended survival to over 120
      days (n = 6). FK506 (1 mg/kg, days 0, 2, 4, 6, 8) too prolonged survival in the
      FK + ITBMC (n = 6; MST > 140 days) and FK (n = 5; MST > 140 days) groups. BN skin
      grafting provoked the rejection of long-surviving BN heart grafts in the FK group
      (n = 5; MST = 14 days), but did not do so in either the ALS + ITBMC (n = 2; MST >
      100 days) or the FK + ITBMC (n = 4; MST > 93 days) groups. In the FK + ITBMC
      group, two of the rats which rejected BN skin grafts received a second BN heart,
      resulting in the graft being accepted indefinitely (> 100 days) without causing
      the rejection of the first BN heart grafts. These facts suggest that ITBMC and
      concurrent T cell depletion are decisive for induction of unresponsiveness by
      this protocol. BN and WF (Wistar Furth) skin grafts were eventually rejected in
      the LEW rats which accepted BN heart grafts. Persistent allogeneic chimerism was
      demonstrated in the graft and recipient spleen, suggesting that chimerism may be
      one of the possible mechanisms of unresponsiveness.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7521739
TI  - The proliferative response of human T cells to allogeneic IFN-gamma-treated
      endothelial cells is mediated via both CD2/LFA-3 and LFA-1/ICAM-1 and -2 adhesion
      pathways.
AB  - We studied the proliferative response of purified human peripheral blood T
      lymphocytes (contaminated with less than 0.1% monocytes) to allogeneic MHC class
      II molecules expressed by endothelial cells (EC) or fibroblasts (FB). In vitro
      expression of MHC class II molecules was induced by gamma-interferon (IFN-gamma)
      treatment. The MHC class II expression levels after IFN-gamma treatment on both
      cell types were comparable. No T cell proliferation was found in the presence of
      either untreated or IFN-gamma-treated FB, and a marginal proliferation in the
      presence of untreated EC. IFN-gamma-treated EC, however, were able to induce
      significant T cell growth. The previously established role of MHC class II
      molecules in allogeneic T cell proliferation was confirmed in inhibition
      experiments with monoclonal antibody (mAb) against MHC class II or CD4. In this
      model, we tested the involvement of a number of adhesion molecules by adding mAbs
      to cocultures of T cells and IFN-gamma-treated EC. Monoclonal antibodies directed
      against CD31, CD26, B7/BB1, E-selectin, CD44, VLA-4 alpha-chain and VCAM-1 had no
      effect, whereas moderate inhibition was observed with anti-VLA-beta-chain and
      anti-LFA-3. A distinct inhibition of T cell proliferation was observed with mAbs
      directed against LFA-1, CD2, or a combination of anti-ICAM-1 and -2. Combinations
      of mAbs directed against T cell adhesion molecules (LFA-1, CD2, VLA-4) or EC
      adhesion molecules (ICAM-1, and -2, LFA-3, VCAM-1) were able to block T cell
      proliferation for 100 and 80% respectively. We conclude that CD2/LFA-3 and LFA
      1/ICAM interactions are crucially involved in allogeneic T cell/EC interactions.

PMID- 7521744
TI  - Microinjection of FITC-dextran into mouse blastomeres to assess topical effects
      of zona photoablation.
AB  - The objective of the current experiments was to investigate whether all or only
      some blastomeres from precompacted mouse embryos were affected by zona
      photoablation. The microbeam of xenon chloride excimer laser (308 nm) was guided
      through an inverted microscope (non-contact system). Topical effects of lasing
      were determined by microinjection of a vital fluorescent dye of high molecular
      weight (fluorescein isothiocyanate [FITC] dextran) into the cell immediately
      adjacent to the site of zona photoablation. This dye is only passed onto daughter
      blastomeres and therefore allows study of specific cell lines. Embryonic growth
      was assessed following cell separation at the morula and blastocyst stage. Four
      cell embryos treated with the laser had significantly fewer cells 12 h after zona
      photoablation than control embryos. A similar effect was noted after 24 h between
      dye injected embryos and those injected and lased simultaneously, indicating
      potential toxic effects of the laser treatment on the embryo. Effects on the
      blastomere closest to the site of ablation were evaluated by calculating the
      ratio of dyed cells to the total number of cells at specific time intervals. The
      ratios were similar in the dye and laser+dye groups of treated 4-cell embryos 36
      h after treatment (0.22 and 0.23, respectively), indicating that the dye was
      still present in approximately 25% of the cells and that the negative effect of
      photoablation was evenly distributed among the blastomeres. It is concluded that
      zona photoablation may have long-term detrimental effects of a non-topical nature
      on precompacted mouse embryos in spite of the apparent precision of the laser
      spot size.

PMID- 7521745
TI  - A molecular screen for polar-localised maternal RNAs in the early embryo of
      Drosophila.
AB  - Localised, maternally synthesised RNAs and proteins play an important role in an
      early animal embryogenesis. In Drosophila, genetic screens have recovered a
      number of maternal effect loci that encode localised products in the embryo.
      However, only a third of Drosophila's genes have been genetically mutated.
      Consequently, we conducted a molecular screen for polar-localised RNAs in the
      early Drosophila embryo in order to identify additional maternal molecules that
      carry out spatially restricted functions during early embryogenesis. Total RNA
      was purified from anterior or posterior poles cut off early Drosophila embryos.
      These RNAs were used to construct directionally cloned anterior and posterior
      cDNA libraries which were used in a differential screen for cDNAs representing
      maternal RNAs localised to one or other pole of the embryo. Five such clones were
      identified, representing cyclin B RNA, Hsp83 RNA, 28S ribosomal RNA,
      mitochondrial cytochrome c oxidase subunit one RNA and mitochondrial 16S large
      ribosomal RNA. Mutations in the loci encoding these RNAs have not been recovered
      in genetic screens, confirming that our molecular approach complements genetic
      strategies for identifying maternal molecules that carry out spatially restricted
      functions in the early embryo. We consider the possible biological significance
      of localisation of each of these species of transcripts as well as the mechanism
      of their localisation, and discuss the potential use of our cDNA libraries in
      screens for rarer localised RNAs.

PMID- 7521746
TI  - Synthesis of di- to penta-saccharides related to the O-specific polysaccharide of
      Shigella dysenteriae type 1, and their nuclear magnetic resonance study.
AB  - The syntheses of oligosaccharide fragments of the O-specific polysaccharide of
      the lipopolysaccharide of Shigella dysenteriae type 1 are described, including
      disaccharides methyl O-alpha-D-mannopyranosyl-(1-->2)-alpha-D-galactopyranoside
      (1), and methyl O-(2-deoxy-2-propionamido-alpha-D-glucopyranosyl)-(1-->3)-alpha-L
      rhamnopyranoside (2), trisaccharide methyl O-alpha-D-galactopyranosyl-(1-->3)-O
      (2-acetamido-2-deoxy-alpha-D- glucopyranosyl)-(1-->3)-alpha-L-rhamnopyranoside
      (3), tetrasaccharide methyl O-alpha-L-rhamnopyranosyl-(1-->2)-O-alpha-D
      galactopyranosyl-(1-->3)- O-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-(1-->3)
      alpha-L-rhamno -pyranoside (4), and pentasaccharide methyl O-alpha-L
      rhamnopyranosyl-(1-->3)-O-alpha-L- rhamnopyranosyl-(1-->2)-O-alpha-D
      galactopyranosyl- (1-->3)-O-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-(1-->3)
      alpha-L- rhamnopyranoside (5). The following monosaccharide building blocks were
      used as starting compounds: methyl 6-O-tert-butyldiphenylsilyl-3,4-O
      isopropylidene-alpha-D-galact opy ranoside (8), methyl 3,4,6-tri-O-benzyl-2-O-(4
      methoxybenzyl)-1-thio-beta-D- galactopyranoside (11), methyl 3,4,6-tri-O-acetyl-2
      azido-2-deoxy-1-thio-alpha- D-glucopyranoside (16), methyl 2-azido-4,6-O
      benzylidene-2-deoxy-1-thio-alpha-D- glucopyranoside (18), methyl 2,4-di-O-benzyl
      alpha-L-rhamnopyranoside (21), methyl 2,3,4-tri-O-benzoyl-1-thio-alpha-L
      rhamnopyranoside (22), 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl bromide (23),
      and methyl 4-O-benzyl-alpha-L-rhamnopyranoside (24). Nuclear magnetic resonance
      data indicate that oligosaccharides 4 and 5 partially mimic the conformation of
      the O-specific polysaccharide of S. dys. type 1.

PMID- 7521743
TI  - FK506 inhibits the differentiation of developing thymocytes but not negative
      selection of T cell receptor V beta 5+ and V beta 11+ T lymphocytes in vivo.
AB  - To examine the influence of FK506 on lymphocyte development, we employed a
      syngeneic bone marrow transplantation model using MHC-disparate B10 (H-2b, I-Ab)
      and B10.BR (H-2k, I-Ak, I-Ek) mice. B10 mice, which do not express class II I-E,
      do not delete any known T cell receptor (TCR)-V beta, while B10.BR mice (MHC
      class II I-Ek, I-Ak) delete V beta 5+ and V beta 11+ TCR. Continuous daily
      treatment of syngeneically reconstituted B10 mice with FK506 delayed the
      development of thymocytes from the CD4+CD8+ to CD4+CD8- stage, while no effect
      was observed at the earlier CD4-CD8- to CD4+CD8+ stage. At the same time, there
      was a significant reduction in TCRhigh thymocytes compared with untreated,
      syngeneically reconstituted controls. These results suggest that FK506 treatment
      interfered with thymic positive selection. We also examined whether FK506
      treatment would influence negative selection. Levels of expression of V beta 5+
      and V beta 11+ T cells in FK506-treated B10.BR-->B10.BR recipients were similar
      to those observed in unmanipulated, syngeneically reconstituted B10.BR-->B10.BR
      controls. This was not due to the inhibition of clonal proliferation by FK506,
      since 35 days after drug withdrawal complete recovery of the peripheral Thy1.2+
      population was observed, while the percentages of V beta 5+ and V beta 11+Thy1.2+
      T cells were maintained at values similar to controls. Surprisingly, clonal
      proliferation stimulated by monoclonal antibody against V beta 5 and V beta 11
      TCRs was observed in CsA-treated, syngeneically reconstituted B10.BR mice but not
      in FK506-treated mice, suggesting that CsA may be more likely to induce
      autoreactivity. Differences in thymic architecture between FK506- and CsA-treated
      animals further suggested that the drugs may differ in their effects on T cell
      development in vivo.

PMID- 7521749
TI  - Evidence against a major role for integrins in calcium-dependent intercellular
      adhesion of epidermal keratinocytes.
AB  - It is well established that integrins mediate keratinocyte adhesion to
      extracellular matrix proteins, but, in addition, there is some evidence that they
      mediate intercellular adhesion. We have investigated the role of integrins in
      keratinocyte-keratinocyte adhesion by adding anti-integrin antibodies to cells in
      three assays that differ according to the calcium ion concentration of the
      medium, the presence or absence of an adhesive substrate (glass or tissue culture
      plastic) and the timing of antibody addition. As previously reported by Larjava
      et al., (J. Cell Biol. 110:803-815), a monoclonal antibody to the beta 1 subunit
      perturbed cell-cell adhesion when added to adherent monolayers in low calcium
      medium (0.1 mM calcium ions), but did not prevent cell-cell adhesion or
      stratification induced by raising the level of calcium ions to 1.8mM (the
      concentration in standard medium). Monoclonal antibodies to both the alpha 3 and
      beta 1 subunits inhibited the attachment, spreading and motility of keratinocytes
      in low or standard calcium medium when added at the time of plating; however,
      they had only a modest effect on the accumulation of cells in adherent clusters.
      Aggregation of keratinocytes in suspension required a calcium ion concentration
      of greater than 0.1mM and was not inhibited by any of a large panel of anti
      integrin antibodies, including three new antibodies that recognise alpha 2 beta
      1. We conclude that any inhibitory effects of individual anti-integrin antibodies
      on cell-cell adhesion are abrogated by a calcium ion concentration above 0.1mM
      and that in low calcium medium at least some of the inhibition of cell-cell
      adhesion is a consequence of the inhibition of cell-substrate adhesion and
      motility.

PMID- 7521748
TI  - The synthesis and use of pp60src-related peptides and phosphopeptides as
      substrates for enzymatic phosphorylation studies.
AB  - A series of peptides and phosphopeptides corresponding to the auto
      phosphorylation site of pp60src, -Asn-Glu-Tyr416-Thr-Ala-, were prepared by
      either Boc/solution or Fmoc/solid phase peptide synthesis and used as substrates
      to study their enzymatic phosphorylation by various casein kinases. The Tyr(P)
      containing peptide, Asn-Glu-Tyr(P)-Thr-Ala, was prepared by the use of Fmoc
      Tyr(PO3Bzl2)-OH in Fmoc/solid phase peptide synthesis followed by acidolytic
      treatment of the peptide-resin with 5% anisole/CF3CO2H. Both Asn-Glu-Tyr-Thr-Ala
      and Asn-Glu-Ser(P)-Thr-Ala were prepared by the Boc/solution phase peptide
      synthesis and employed hydrogenolytic deprotection of the protected peptides.
      Enzymatic phosphorylation studies established that (A) the Tyr residue acted as
      an unusual positive determinant for directing phosphorylation to the Thr-residue,
      (B) the rate of Thr-phosphorylation was markedly facilitated by a change from the
      Tyr-residue to the Tyr(P)-residue, and (C) a Ser(P)-residue was as effective as
      the Tyr(P)-residue in facilitating Thr-phosphorylation. A subsequent structure
      function study using Asn-Glu-Phe-Thr-Ala, Asn-Glu-Tyr(Me)-Thr-Ala (prepared by
      Fmoc/solid phase peptide synthesis) and Asn-Glu-Cha-Thr-Ala (prepared by
      hydrogenation of Asn-Glu-Tyr-Thr-Ala) established that the rate of Thr
      phosphorylation was influenced by the extent of hydrophobic-hydrophobic
      interactions by the aralkyl side-chain group (either aromatic or aliphatic) of
      the 416-residue with casein kinase-2; the rate of Thr-phosphorylation being
      decreased by the introduction of methyl or hydroxyl groups at the 4-position of
      the aromatic group (i.e. Tyr(Me) and Tyr respectively) but enhanced by the
      introduction of the hydrophilic phosphate group (i.e. as Tyr(P)).

PMID- 7521750
TI  - A glycoprotein expressed by human fibrous astrocytes is a hyaluronate-binding
      protein and a member of the CD44 family.
AB  - We have isolated and characterized an antigen from normal human brain called p80,
      so called because it migrated with an M(r) of 80 kDa on SDS PAGE. The M(r) of 80
      kDa consists of a protein of about 55-60 kDa and carbohydrate (20-25 kDa). The
      carbohydrate is almost entirely of the N-linked type, although a small amount of
      O-linked carbohydrate was detected. Cross-reactivity with monoclonal antibodies
      A3D8 and A1G3 showed that p80 could therefore be considered an isoform of the
      CD44 adhesion molecules. In addition, specific binding to hyaluronate which was
      not competed for by proteoglycan demonstrated that it involved different sites
      than the proteoglycan binding sites. We also observed that fucoidan and dextran
      sulphate increased the binding by 200-250% while chondroitin sulphate C also
      increased the binding but to a lesser extent. Heparin, heparan sulphate and
      chondroitin sulphates A and B did not have such an effect. The binding of p80 to
      hyaluronate was pH dependent with a maximum at pH 6.4. We concluded that p80 was
      an astrocyte specific adhesion molecule.

PMID- 7521747
TI  - Enzymic acylation of methyl D- and L-glycopyranosides: influence of the 3
      hydroxyl group.
AB  - Porcine pancreatic (PPL), Candida cylindracea (CCL) and Pseudomonas cepacia (LPS)
      lipases, suspended in organic solvents, were used to regioselectively acylate
      methyl 6-O-butyryl-alpha-D- and L-allopyranosides and methyl 6-O-butyryl-3-deoxy
      alpha-D- and L-ribo-hexopyranosides. Both the D- and the L-3-deoxy sugars showed
      a complete regioselectivity, while the reactions of the allosides proved to be
      less regioselective. This indicates that the presence of the hydroxyl group at C
      3 is an unfavourable factor for the action of the lipases.

PMID- 7521751
TI  - Inhibitors of topoisomerase II prevent cytokine-induced expression of vascular
      cell adhesion molecule-1, while augmenting the expression of endothelial
      leukocyte adhesion molecule-1 on human umbilical vein endothelial cells.
AB  - Cytokine stimulation of human umbilical vein endothelial cells (HUVE) induces
      surface expression of the adhesion molecules vascular cell adhesion molecule-1
      (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and endothelial leukocyte
      adhesion molecule-1 (E-selectin). We previously found that induction of adhesion
      molecule expression in HUVE is regulated, at least in part, by protein kinase C
      (PKC) activation, although this is not associated with the expected translocation
      of PKC from the cytosolic to the particulate fraction. We therefore investigated
      potential nuclear targets for PKC. Topoisomerase II is localized to the nuclear
      matrix and has been shown to be phosphorylated, both in vitro and in vivo, by
      PKC. In HUVE, the topoisomerase II selective inhibitors novobiocin, nalidixic
      acid, and etoposide prevented cytokine-induced VCAM-1 surface expression, but not
      E-selectin or ICAM-1 surface expression. Similarly, novobiocin and nalidixic acid
      reduced the accumulation of VCAM-1 mRNA in response to tumor necrosis factor
      alpha treatment of HUVE. The inhibitory effect of the topoisomerase II inhibitors
      on VCAM-1 expression was not due to non-specific toxicity, as protein synthesis,
      measured by trichloroacetic acid precipitation of 35S-methionine labeled
      proteins, and transcription, determined by beta-actin mRNA levels, were not
      decreased. In contrast to the observed reduction of VCAM-1 mRNA accumulation and
      surface protein expression, inhibition of topoisomerase II activity enhanced E
      selectin mRNA accumulation and surface protein expression in response to tumor
      necrosis factor-alpha stimulation of HUVE. This work demonstrates that
      topoisomerase II activity may differentially regulate the expression of adhesion
      molecules on HUVE.

PMID- 7521752
TI  - Evidence for the binding of Ng-CAM to laminin.
AB  - Ng-CAM is a cell adhesion molecule mediating neuron-glia and neuron-neuron
      adhesion via different binding mechanisms. While its binding can be homophilic as
      demonstrated by the self-aggregation of Ng-CAM coated beads (Covaspheres), Ng-CAM
      has also been shown to bind to glia by a heterophilic mechanism. In the present
      study, we found that the extent of Ng-CAM Covasphere aggregation was strongly
      diminished in the presence of the extracellular matrix glycoprotein laminin. When
      proteolytic fragments of laminin were tested, the P1' fragment (obtained from the
      short arms by pepsin treatment) was found to inhibit aggregation of Ng-CAM
      Covaspheres while the elastase fragments E3 and E8 (from the long arm) were
      ineffective. To provide other means of analyzing interactions between laminin and
      Ng-CAM, the two proteins were covalently linked to differently fluorescing
      Covaspheres and tested for coaggregation. Laminin-Covaspheres coaggregated with
      Ng-CAM-Covaspheres, and this binding was inhibited both by anti-Ng-CAM and by
      anti-laminin antibodies. Covaspheres coated with other proteins including BSA and
      fibronectin did not coaggregate with Ng-CAM-Covaspheres. Moreover, using a solid
      phase binding assay, we found that 125I-labeled Ng-CAM bound to laminin and to Ng
      CAM but not to fibronectin. The results suggest that regions in the short arms of
      laminin can bind to Ng-CAM. To test whether Ng-CAM present on neurons could be
      involved in binding to laminin, adhesion of neurons to substrates coated with
      various proteins was tested in the presence of specific antibodies. Anti-Ng-CAM
      Fab' fragments inhibited neuronal binding to laminin but not binding to
      fibronectin. The combined results open the possibility that Ng-CAM on the surface
      of neurons may mediate binding to laminin in vivo, and that interactions with
      laminin can modulate homophilic Ng-CAM binding.

PMID- 7521754
TI  - The beta 1 integrin distal promoter is developmentally regulated in transgenic
      mice.
AB  - Transgenic mice harbouring 5' flanking sequences of the human beta 1 integrin
      gene linked to the Escherichia coli lacZ gene have been generated to examine
      spatial and temporal distribution of the promoter activity during development.
      Our previous data showed that this regulatory region is composed by two
      promoters, called distal and proximal, located closely on the human genome. To
      determine the role of each promoter region during development we generated
      transgenic mice using these two sequences linked to the lacZ reporter gene. Their
      analysis shows that these two sequences, as determined by in vitro studies, have
      different efficiencies in promoting transcription. Actually mice carrying the
      proximal promoter region exhibit a weak lacZ expression resulting in an
      undetectable beta-galactosidase activity in both embryonic and adult tissues. On
      the other hand, transgenic mice carrying the distal promoter express beta
      galactosidase at high efficiency during embryonic development. The pattern of
      transgene expression is consistent with the localization of beta 1 protein on
      mouse embryos evidenced by immunohistochemistry. Moreover the distal promoter is
      subjected to a temporal modulation since in adult transgenic mice lacZ expression
      decreases to a level detected only by RT-PCR analysis. We have determined a
      similar down-regulation analysing by Northern blot beta 1 mRNA in adult and
      embryonic organs such as heart and gut.

PMID- 7521753
TI  - Evaluation of integrin molecules involved in substrate adhesion.
AB  - Integrins were cross-linked to their extracellular matrix ligands using non
      penetrating chemical cross-linkers. This procedure did not disturb the
      distribution of integrin in the adhesion structure and adhesion plaque integrin
      staining remained even when the cultures were extracted with ionic detergents. 80
      90% of the beta 1 integrin in the cross-linked culture was extracted with RIPA
      buffer and the remaining 10-20% was recovered following reversal of the cross
      linking. This separated two distinct integrin pools, one which can be cross
      linked to substrate bound extracellular matrix and one which is not. The
      specificity of this procedure for cross-linking of integrins involved in
      substrate adhesion was demonstrated using NIH 3T3 cells which express both alpha
      5 beta 1 and alpha 6 beta 1 integrins. alpha 6 was cross-linked only in cells
      plated on laminin whereas alpha 5 was cross-linked when fibronectin was present.
      Using antisera directed to the cytoplasmic domains of either alpha 5 or beta 1
      integrin, it was demonstrated that these domains can be blocked in the intact
      cell but the blocking can be removed using ionic detergent extraction after
      chemical cross-linking. The extracellular matrix associated with the substrate
      surface but not that associated with the media exposed surface is both cross
      linked and retained on the plastic dish following cross-linking.

PMID- 7521755
TI  - Vasoactive intestinal peptide (VIP) inhibits substrate adherence capacity of rat
      peritoneal macrophages by a mechanism that involves cAMP.
AB  - In this study, vasoactive intestinal peptide (VIP) is shown to inhibit substrate
      adherence capacity of rat peritoneal macrophages. The inhibitory response
      occurred in the 0.1-1,000 nM range of VIP concentrations and it was a time
      dependent process. At 15 min, half maximal inhibition (IC50) was obtained at 0.37
      +/- 0.26 nM and maximal inhibition (53.8%) at 10(-6) M VIP. The inhibitory effect
      of VIP was correlated with the stimulation by this peptide of cyclic AMP (cAMP)
      production in rat peritoneal macrophages. Moreover, agents that inhibited VIP
      stimulated cAMP production, such as the VIP-antagonist [4-Cl-D-Phe6, Leu17]-VIP
      and somatostatin, also decreased the inhibitory effect of VIP on substrate
      adherence capacity of macrophages. On the contrary, the phosphodiesterase
      inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the lipid-soluble derivative of
      cAMP N6,2'-O-dibutyryl cAMP (Bu-cAMP) inhibited the adherence of macrophages to
      substrate and potentiated the inhibitory action of VIP. These results demonstrate
      that VIP inhibits substrate adherence capacity of rat peritoneal macrophages by a
      mechanism that involves cAMP, and show, for the first time, an action of VIP on
      the function of peritoneal macrophages.

PMID- 7521756
TI  - Functional properties of alternatively spliced forms of the Drosophila PS2
      integrin alpha subunit.
AB  - The Drosophila alpha PS2 protein is encoded by two alternatively spliced
      transcripts. The respective alpha PS2 proteins differ by the presence of 25 amino
      acids in the alpha PS2(C) protein, not found in the alpha PS2(m8) subunit, in a
      region thought to be important for ligand binding. We examined the functional
      properties of Drosophila S2 cells transformed with genes expressing either of
      these proteins, in association with a beta PS subunit. Both PS2 integrins support
      cell spreading on vertebrate vitronectin or, to a lesser extent, on fibronectin.
      Interestingly, the PS2(C) form promotes spreading more efficiently on vitronectin
      than does the PS2(m8) form, with an opposite relative efficiency seen for
      fibronectin. Also, the two forms of PS2 show different requirements for divalent
      cations in order to mediate efficient cell spreading. These divalent cations are
      not required to maintain the association of alpha and beta subunits. Spreading of
      both cell types is similarly RGD sensitive, and both PS2 integrins appear to
      associate with the actin cytoskeleton. To our knowledge, this represents the
      first demonstration of functional differences in integrin subunits resulting from
      splicing variation to generate different extracellular, ligand binding domains.

PMID- 7521757
TI  - Alpha v beta 5 integrin is localized at focal contacts by HT-1080 fibrosarcoma
      cells and human skin fibroblasts attached to vitronectin.
AB  - In this study we characterized alpha v beta 5 integrin on HT-1080 fibrosarcoma
      cells. First, alpha v beta 5 integrin was immunoprecipitated by 125I-surface
      labeled HT-1080 cells using a polyclonal antibody specific for beta 5 subunit
      (cytoplasmic domain). A heterodimer consisting of a beta 5-chain running at 100
      kD (reduced) and 90 kD (non-reduced) associated with an alpha-chain 145 kD (non
      reduced) and 125 kD (reduced) was obtained by SDS-PAGE and autoradiography. By
      double-immunofluorescence labeling, we then investigated alpha v beta 5
      distribution on HT-1080 cells. Upon staining with anti-beta 5 subunit antibody,
      alpha v beta 5 was detected in focal contacts on cells attached to vitronectin
      (vn), co-localizing with vinculin at the end of actin filaments. Comparative
      analysis of alpha v beta 5 and alpha v beta 3 showed that both receptors can
      occupy the same focal contact, although on the same cell mostly they are
      clustered in independent focal contacts. Focal distribution of alpha v beta 5 was
      also found on normal human fibroblasts attached to vn, suggesting that this is
      not a specific feature of HT-1080 cells. Finally, we investigated the role of
      alpha v beta 5 and alpha v beta 3 integrins in mediating HT-1080 cell adhesion to
      vn. Inhibition studies using antibodies with function-blocking activity to alpha
      v beta 5 and alpha v beta 3 suggest a primary role of alpha v beta 5 to support
      cell adhesion, with a weak contribute of alpha v beta 3. Their activity can be
      modulated by divalent cations. Our results provide the first evidence of focal
      distribution of alpha v beta 5 integrin on cells attached to vn.

PMID- 7521759
TI  - Anti-beta 1 integrin IgG inhibits pulmonary macrometastasis and the size of
      micrometastases from a murine mammary carcinoma.
AB  - In the present report, we investigated the possible importance of beta 1
      integrins in the growth and metastasis of a murine mammary carcinoma, SP1, and a
      metastatic variant, SP1-3M in vivo. CBA/J female mice bearing SP1 tumor
      transplants were injected with anti-beta 1 integrin IgG or control nonimmune IgG
      (200 micrograms per mouse; i.p.) every two days. Animals received anti-CD4
      antibody (100 micrograms per mouse) at time zero to suppress immunity against
      rabbit IgG. Outgrowth of macroscopic metastases from SP1, but not from SP1-3M
      primary tumors, was markedly inhibited in animals receiving anti-beta 1 integrin
      IgG but not nonimmune IgG. To assess the stage(s) in the metastatic cascade
      affected, we examined the number and diameter of micrometastatic nodules in
      treated and untreated groups. The diameter of micrometastases was significantly
      reduced in SP1-tumor-bearing mice treated with anti-beta 1 integrin IgG compared
      to control IgG, although the number of nodules per cm2 of lung sections examined
      remained unchanged. No change in the number or size of micrometastases in SP1-3M
      tumor-bearing mice was observed. No difference in the binding, or complement
      mediated and antibody-dependent cell-mediated cytotoxicity of anti-beta 1
      integrin IgG with SP1 and SP1-3M cells was detected. The results suggest that
      under these conditions anti-beta 1 integrin inhibits metastatic tumor growth in
      lung tissue, but has minimal effect on intravasation, adhesion to target organs
      and extravasation.

PMID- 7521760
TI  - Borrelia burgdorferi upregulates the adhesion molecules E-selectin, P-selectin,
      ICAM-1 and VCAM-1 on mouse endothelioma cells in vitro.
AB  - In order to obtain more information on processes leading to Borrelia burgdorferi
      induced inflammation in the host, we have developed an in vitro model to study
      the upregulation of cell surface expression of adhesion molecules on endothelial
      cells by spirochetes. A mouse endothelioma cell line, derived from brain
      capillaries, bEnd3, was used as indicator population. bEnd3 cells were incubated
      with preparations of viable, inactivated or sonicated spirochetes and the
      expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 was monitored by
      immunocytochemistry and quantified by cell surface ELISA. We show that all three
      spirochetal preparations are able to upregulate cell surface expression of E
      selectin, P-selectin, ICAM-1 and VCAM-1 on bEnd 3 cells in a dose-dependent
      manner. The kinetics of cell surface expression of the individual adhesion
      molecules in the presence of Borrelia burgdorferi showed maxima at about 50 h of
      incubation or later; this was distinct from results obtained with sonicated
      preparations of Escherichia coli bacteria or with enterobacterial LPS where peak
      expression was observed between 4 h and 16 h. The fact that Borrelia burgdorferi
      does not contain conventional LPS suggests that the mode of induction of adhesion
      molecules on endothelial cells is influenced by the phenotype of bacteria. At the
      peak of spirochete-induced cell surface expression of adhesion molecules
      (approximately 50 h), bEnd3 cells were found to bind cells of a VLA-4+ B lymphoma
      line (L1-2) much more efficiently than untreated control cells. The binding of L1
      2 cells to presensitized bEnd3 cells was significantly inhibited (more than 75%)
      in the presence of monoclonal antibodies to both VLA-4 and its endothelial
      counterreceptor VCAM-1. These findings demonstrate that Borrelia burgdorferi
      organisms are able to induce functionally active adhesion molecules on
      endothelial cells in vitro and suggest that E-selectin, P-selectin, ICAM-1 and
      VCAM-1 play an important role in the pathogenesis of spirochetal infection.

PMID- 7521758
TI  - Cell-cycle dependent alternative splicing of the tenascin primary transcript.
AB  - Functionally different tenascin (TN) isoforms may be generated by alternative
      splicing of the TN primary transcript. In fact, it has been demonstrated that
      only the larger TN isoform containing the alternatively spliced region induces
      loss of focal adhesion in cultured cells and seems able to facilitate cell
      migration. Recent studies have shown that the higher molecular mass TN isoform is
      a marker of stromal cell proliferation in hyperplastic and neoplastic breast
      tissues. This finding prompted us to study the pattern of TN alternative splicing
      in proliferating and non-proliferating cultured fibroblasts. Here, we show that
      the mitogenic stimulation of fibroblasts with serum or cytokines leads to an
      early and striking modification in the steady-state levels of the two major TN
      mRNAs. We also show that de novo protein synthesis is not necessary for this
      modification, indicating that it is a "primary response" event. Similarly,
      mitogenic stimulation induces changes both in synthesis and accumulation of the
      different TN isoforms.

PMID- 7521761
TI  - Distribution of integrin subunits in normal human kidney.
AB  - We evaluated on serial sections the distribution of a large number of integrin
      alpha and beta chains in normal adult human kidney: 1) the beta 1 chain and its
      corresponding alpha subunits (alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, alpha
      6), 2) alpha v and beta 3 chains, 3) the beta 2 chain and its corresponding alpha
      chains (alpha X, alpha M, alpha L), and 4) the beta 4 chain. We also evaluated
      ICAM-1, VCAM and ELAM and the major extracellular matrix components (ECM). A
      three step immunoperoxidase technique was used on frozen sections. Each cell of
      the kidney shows a specific distribution of these molecules. The relation with
      ECM and some of their ligands was evaluated. This immunohistochemical study shows
      that there is no strict colocalisation of a given ECM component with its specific
      receptor.

PMID- 7521762
TI  - MAb 18D3 triggering of integrin beta 1 will prevent but not terminate
      proliferation of human T cells.
AB  - Triggering of integrins can deliver signals that will regulate T cell activation
      and proliferation when coupled with TCR/CD3 signaling. While co-activation
      stimuli can be achieved either with immobilized natural ligands or immobilized
      monoclonal antibodies specific for various integrin subunits, counterposing
      effects can be delivered by ligation of the integrin beta 1 chain (CD29)
      resulting in the downregulation of T cell proliferation. Thus, integrins may play
      a pivotal role in cell activation and are involved in both positive and negative
      regulatory pathways. In this report, anti-beta 1 mAb 18D3 was used to investigate
      the role of beta 1 in the negative regulation of T cell proliferation. T
      lymphocytes were stimulated to proliferate when activated with immobilized mAb to
      CD3 in conjunction with all of a panel of immobilized mAb to different alpha 4
      (CD49d) and beta 1 epitopes, except the anti-beta 1.1 mAb 18D3. In soluble form,
      mAb 18D3 inhibited the induction of DNA synthesis dependent on costimulation of
      CD3 and the integrin alpha 4 subunit by a mechanism independent of anti-adhesive
      properties. In kinetic experiments, the addition of mAb 18D3 effectively
      inhibited the ultimate induction of DNA synthesis at all time points until the
      time coinciding with the onset of T cell proliferation, indicating that
      triggering the beta 1.1 epitope may only act to quench activation events prior to
      cellular commitment to synthesize DNA. MAb 18D3 did not induce cell death nor
      render cells incompetent for restimulation, but appeared to selectively inhibit
      IL-2 synthesis with little effect on the induction of IL-2 receptor expression.

PMID- 7521764
TI  - Thoracoscopic oesophago-gastrectomy--a new technique for intra-thoracic stapling.
AB  - A new technique for performing a standard Ivor Lewis oesophagectomy avoiding the
      need for a conventional right thoracotomy is described. The intrathoracic
      dissection and the intrathoracic anastomosis, using a conventional EEA circular
      staple-gun, is done thoracoscopically. Eight patients with carcinoma of the
      gastric cardia or distal oesophagus were prepared for a palliative Ivor Lewis two
      stage oesophago-gastrectomy. The details of the technique for placing the anvil
      of a circular staple gun in the upper oesophagus and performing the intrathoracic
      stapled anastomosis are described. Intrathoracic stapling under thoracoscopic
      video control was successful in five of the eight patients. The three other
      patients received 10 cm mini-thoracotomies. All patients were transferred from
      the intensive care unit within 24 hours and were discharged from hospital within
      14 days. There were no complications and no deaths. We believe that this
      procedure offers many patients better palliation with reduced morbidity because
      the standard right thoracotomy is avoided.

PMID- 7521765
TI  - General cystic fibrosis mutations are usually missense mutations affecting two
      specific protein domains and associated with a specific RFLP marker haplotype.
AB  - Some 250 different mutations have so far been screened in the cystic fibrosis
      (CF) gene. The 50 nonsense, 33 splicing and 60 frameshift mutations are randomly
      distributed within the gene, unlike the 107 missense mutations or amino acid
      deletions. A large excess of missense mutations affects the exons encoding the
      first transmembrane (MS1) and first ATP-binding fold (NBF1) domains. Sixty-four
      of the 107 missense mutations may be classified as private, demic, local and
      general mutations on the basis of their geographic distribution in Europe.
      Private and demic mutations are randomly distributed within the gene; local and
      general mutations are not. It is well known that some RFLP markers are in linkage
      disequilibrium with some mutations. Private, demic and local mutations are
      randomly associated with each class of RFLP haplotypes. In contrast, general
      mutations, frequent and infrequent, are not randomly associated with RFLP
      markers. General mutations usually affect a specific part of the gene and are
      more likely to be associated with a specific RFLP marker. This suggests the
      existence of selective factors favoring these mutations, a hypothesis formerly
      postulated as a possible cause of the high frequency of the disease.

PMID- 7521763
TI  - Activation dependent and independent VLA-4 binding sites on vascular cell
      adhesion molecule-1.
AB  - Vascular cell adhesion molecule-1 (VCAM) is a cytokine-inducible member of the
      immunoglobulin superfamily which binds to the integrin VLA-4. VCAM is expressed
      predominantly on the vascular endothelium where it is involved in the recruitment
      of mononuclear cells and lymphocytes to sites of inflammation. Two forms of VCAM
      containing six and seven Ig domains (VCAM-6d; VCAM-7d) are generated by
      alternative splicing but the physiological significance of this is unknown. We
      have utilised VCAM deletion mutants, VCAM-transfected cell lines and monoclonal
      antibodies to assess the functional importance of the individual VCAM domains. We
      have identified two binding sites on VCAM-7d located in domains 1 and 4 that are
      involved in the adhesion of the U937 human myelomonocytic cell line. Adhesion to
      domain 1 is temperature-independent, inhibited by the anti-VCAM mAbs 4B2 or lE10,
      and insensitive to PMA activation. In contrast, adhesion to domain 4 is
      temperature sensitive, unaffected by mAbs 4B2 or lE10 and augmented by PMA.
      Adhesion to both domains can be totally inhibited by the anti-VLA-4 mAb, 2B4. The
      anti-VCAM mAb 4B2 inhibits adhesion of U937 cells to stably transfected VCAM-7d
      CHO cells at 4 degrees C, but, at 37 degrees C the effect of 4B2 on adhesion is
      modest with incubation times of less than 60 minutes duration. With longer
      incubation times, its effectiveness gradually increases, so that by 2 hours > 75%
      of the response can be blocked. Co-incubation with PMA prevents this time
      dependent enhancement of 4B2 efficacy but has no significant effect on the
      inhibitory activity of the anti-VLA-4 mAb 2B4. These data can be explained by
      postulating a two stage ligand-receptor interaction that involves activation
      induced changes in the avidity of VLA-4 for domain 4 of VCAM.

PMID- 7521768
TI  - Insulin-like growth factor I and the kidney: friend or foe?

PMID- 7521767
TI  - Species differences in mammalian renal function: 5-HIAA, a reported marker of
      tubular secretion in humans, is handled exclusively by filtration in the rat.
AB  - Renal clearance of endogenous 5-HIAA has been shown to be similar to that of PAH
      in humans. The present study compared 5-HIAA and PAH clearances in rats. It
      showed that the clearance of 5-HIAA in rats was identical to that of inulin and
      creatinine. This suggests that in this species, 5-HIAA is only filtered and not
      secreted by the tubules in contrast to what is observed in humans.

PMID- 7521769
TI  - Cyclic nucleotides inhibit Na+/Ca2+ exchange in cultured human mesangial cells.
AB  - Na+/Ca2+ exchange contributes to the control of cytosolic free Ca2+ levels
      ([Ca2+]i) in resting and activated cultured human mesangial cells. We have
      previously shown that activation of phospholipase C by vasoconstrictors enhances
      Ca2+ influx upon extracellular Na+ withdrawal. This effect is not mediated by
      concurrent activation of protein kinase (PK) C, since it occurs even after PKC
      inhibition, and phorbol esters actually blunt both basal and stimulated Na+/Ca2+
      exchange. We now studied the effects of PKA and PKG activation by
      adenylate/guanylate cyclase stimuli or by permeant analogues of cyclic
      nucleotides in monolayer cultures loaded with the fluorescent Ca(2+)-sensitive
      probe, fura-2. The exchanger was inhibited by the stable prostaglandin I2
      analogue, iloprost, which is transduced by cAMP (peak [Ca2+]i inhibition by 1
      microM iloprost 35 +/- 3%). Similarly, non-receptor activation of adenylate
      cyclase by 10 microM forskolin inhibited basal and agonist-stimulated Na+/Ca2+
      exchange by 52 +/- 4 and 66 +/- 4%, respectively. Dibutyryl-cAMP (0.1 mM) also
      inhibited stimulated Na(+)-dependent Ca2+ influx by 72 +/- 2%. The particulate
      guanylate cyclase agonist, atriopeptin III, and the soluble guanylate cyclase
      activator, glyceryltrinitrate, also inhibited both basal and angiotensin II
      stimulated Na+Ca2+ exchange (to a maximum of 53 +/- 5 and 62 +/- 3%,
      respectively). Dibutyryl-cGMP (1 mM) mimicked the effects of cGMP stimuli,
      reducing stimulated Na+/Ca2+ exchange by 79 +/- 2%. Therefore, similar to PKC,
      cyclic nucleotide activation of PKA and PKG regulates Na+/Ca2+ exchange,
      providing a functional link between transmembrane signalling systems for
      vasoactive agents in cultured human mesangial cells.

PMID- 7521770
TI  - A diffusion immunogold procedure for accurate ultrastructural investigation of
      renal cell membrane epitopes.
AB  - A role for renal antigenic targets has been supposed and sometimes convincingly
      demonstrated in the development of various types of experimental
      glomerulonephritides. In this report we describe a reliable protocol for accurate
      ultrastructural investigation of antigens on the renal cell surface by means of a
      pre-embedding technique associated with colloidal gold staining. Sprague-Dawley
      rats were injected with a monoclonal antibody specific for a 90-kD cell membrane
      glycoprotein and killed 12 or 48 h later; after prefixation, renal fragments were
      cryoprotected and snap-frozen. Cryostat sections were incubated with a 5-nm
      colloidal gold-goat antimouse antibody, postfixed in osmium tetroxide reduced
      with potassium ferrocyanide and embedded in Durcupan ACM. At the glomerular
      level, gold granules were localized on the endothelial cell surface. In the
      proximal tubules uniform labelling was noticed on the brush border microvilli,
      followed by later marking of the basolateral membranes. By this pre-embedding
      immunogold method we obtained suitable histological preservation and fine
      resolution of the cell membrane immunoreactive sites. This procedure represents a
      useful tool for ultrastructural studies on the interaction of circulating
      antibodies with renal cell surface antigens.

PMID- 7521766
TI  - Glomerular NO synthase activity in mesangial cell immune injury.
AB  - Ex vivo synthesis of nitrite (NO2-) by nephritic glomeruli provides evidence of
      induction of nitric oxide (NO) in glomerulonephritis (GN). In macrophage
      associated GN, the major source is infiltrating macrophages. As induction of NO
      synthesis has now been shown in cultured mesangial cells, we have examined
      whether in vivo mesangial proliferation is a source of NO2-. Mesangial
      proliferative GN was induced by intravenous anti-Thy1.1 (monoclonal antibody
      ER4). Isolated glomeruli were assayed for NO2- synthesis and macrophage
      infiltration on day 4 (mesangiolytic phase) and on day 7 (mesangial
      proliferation). On day 4, but not on day 7, basal NO2- was increased (8.3 +/-
      1.8, controls 0.7 +/- 0.1 nmol/2,000 glomeruli/48 h; p = 0.05) and there was
      macrophage infiltration (60 +/- 15; controls 14 macrophages/glomerulus). At both
      times NO2- was elevated by exogenous IL1 or LPS, more significantly on day 4 than
      on day 7. Thus, mesangial proliferative lesions are not a source of basal NO2-,
      and macrophages are the most likely source. However, NO2- can be induced in
      mesangial proliferative glomeruli by exogenous stimuli, findings similar to those
      reported in cultured mesangial cells. Irradiation experiments in normal rats show
      that stimulated NO2- synthesis is inhibited by macrophage depletion. Therefore in
      neither normal nor proliferative glomeruli is there evidence for mesangial cell
      production of NO2-.

PMID- 7521771
TI  - Interaction between atrial natriuretic peptide and angiotensin II in cultured
      glomerular mesangial cells and its disturbance in diabetes.

PMID- 7521772
TI  - Regulation of mesangial cell proliferation by purinergic ligands.

PMID- 7521773
TI  - Inflammatory mediators induce the production of nitric oxide in vascular smooth
      muscle.

PMID- 7521775
TI  - Effects of altered nitric oxide synthesis and of exogenous nitric oxide on the
      proliferation of mesangial cells in culture.

PMID- 7521774
TI  - Cytokine regulation of nitric oxide synthase expression in glomerular mesangial
      cells.

PMID- 7521776
TI  - Transduction pathways for growth stimulatory and inhibitory actions of vasoactive
      agents.

PMID- 7521777
TI  - Demonstration of peptidergic afferents to the bed nucleus of the stria terminalis
      using local injections of colchicine. A combined immunohistochemical and
      retrograde tracing study.
AB  - In the present study, we demonstrate the existence of numerous peptidergic
      afferents to the bed nucleus of the stria terminalis (BNST) using the retrograde
      transport of gold-labeled wheat germ agglutinin-apo-peroxidase (G-WGA-HRP)
      combined with the indirect immunoperoxidase method after intraparenchymatous
      injections of colchicine. At first, we show that local injections of colchicine
      alone into the BNST are able to induce the retrograde accumulation of peptides
      until the nerve cell bodies of origin, probably because of the blockade of axonal
      transport in nerve terminal arborizations innervating this nucleus. The actual
      existence of putative peptidergic afferents to the BNST indicated by the local
      injections of colchicine was established using: a) the retrograde transport of G
      WGA-HRP from the BNST combined with immunocytochemistry after administration of
      colchicine at the same place, b) the anterograde "transport" of the fluorescent
      tracer DiI from selected nuclei of the forebrain. We demonstrate that the neurons
      immunoreactive for enkephalins, neurotensin, or substance P that innervate the
      BNST are localized mainly in the central amygdaloid nucleus, the paraventricular
      thalamic nucleus, and the ventromedial hypothalamic nucleus ipsilateral to the
      injection, as well as bilaterally in the magnocellular paraventricular and
      perifornical regions of the hypothalamus. From these results it may be concluded
      that intracerebral injections of colchicine constitute a powerful tool to search
      for multiple peptidergic afferents to a given brain nucleus using only
      immunohistochemistry. The existence of these pathways, however, must be verified
      by other neuroanatomical methods because of the problem of nerve fibers of
      passage.

PMID- 7521778
TI  - Morphology and projections of neurobiotin-labeled nucleus tractus solitarii
      neurons recorded in vitro.
AB  - The suitability of the anterograde tracer neurobiotin to provide information
      about the morphology and projections of extracellularly or intracellularly
      recorded medial nucleus tractus solitarii (nTS) neurons was evaluated in
      horizontally oriented rat dorsal medulla in vitro slices. After responsiveness to
      angiotensin (Ang) II, substance P (SP), and L-glutamate was evaluated, neurons
      were labeled by electrophoresis of neurobiotin at the recording site.
      Extracellular application (2 microA for 2 min) produced discrete injection sites
      (40-70 microns) with a small group of labeled neurons. Ejections into the
      solitary tract documented that the tracer was not taken up by axons traversing
      the injection site. Neuronal perikarya, primary and secondary dendrites, and
      axons exhibited a dense Golgi-like appearance, with well-defined dendritic spines
      and axonal varicosities. Dendritic or axonal processes could be followed for more
      than 1 mm from the cell soma in a 50 microns thick section, documenting the
      horizontal architecture of the medial nTS. Intracellular electrophoresis filled
      the soma, primary and secondary dendrites, and axons of neurons characterized for
      responsiveness to peptides, L-glutamate and solitary tract stimulation. The
      location within the nTS and axonal projections of neurons responsive to Ang II
      and SP appeared to differ from those of cells responsive to Ang II and L
      glutamate. Thus, either extracellular or intracellular application of neurobiotin
      in the in vitro slice can reveal differences in axonal or dendritic targets of
      neuronal subgroups responsive to different neurotransmitters or peptides and
      provide evidence for the likely autonomic significance of the neurons.

PMID- 7521779
TI  - Distribution of substance P-like immunoreactivity in the chameleon brain.
AB  - The distribution of substance P-like immunoreactivity in the chameleon brain and
      spinal cord was studied with immunohistochemical methods using polyclonal
      antibodies against substance P. In the telencephalon, immunoreactive cell bodies
      and fibers were located primarily in the striatum and in the globus pallidus. In
      addition, few substance P-like fibers were observed in the cortical areas, in the
      septum, and in the amygdala. In the diencephalon, a high density of immunostained
      neurons and fibers were seen in the periventricular and ventrolateral
      hypothalamus. Another group of cell bodies was located in the optic tectum and
      particularly in the stratum griseum central. A large number of immunoreactive
      fibers were also detected in the thalamic nuclei and in the median eminence. In
      the mesencephalon, few immunoreactive neurons were observed in the ventral
      tegmental area, in the substantia nigra, and in the nucleus reticularis isthmi.
      These latter nuclei, the periventricular area, the posterior commissure, the
      nucleus lentiformis mesencephali, the oculomotor nucleus, and the raphe nuclei
      contained a dense plexus of substance P immunoreactive fibers. No immunoreactive
      cell bodies were observed in raphe nuclei. In the spinal cord, no substance P
      like immunoreactive neurons were observed, but a large number of substance P
      immunostained fibers were seen in the dorsal and lateral part of the dorsal horn
      and surrounding the dorsal parts of the central canal. The results of the present
      study are discussed with respect to those obtained in other species of reptiles,
      the main differences concerning the lateral septum, the habenula, the area of the
      paraventricular organ, and the raphe nuclei.

PMID- 7521782
TI  - Standardization of immunoassays for prostate specific antigen. A different view
      based on experimental observations.

PMID- 7521781
TI  - Current and future directions regarding quality assurance and standardization of
      prostate specific antigen immunoassays.

PMID- 7521783
TI  - Prostate specific antigen and prostate specific antigen density. Roles in patient
      evaluation and management.
AB  - Prostate specific antigen (PSA) is the most accurate serum marker for prostate
      cancer. However, sensitivity and specificity are suboptimal, especially at the
      intermediate levels between 4.1 and 10.0 ng/ml (monoclonal). For intermediate PSA
      levels, PSA density (PSAD) provides unique information regarding the need for
      biopsy and the likelihood of prostate cancer. The authors prospectively used PSAD
      to determine the need for biopsy in 68 patients with PSAD values below 0.150 and
      normal results from a digital rectal examination. Ten patients have undergone
      biopsy secondary to a rising serum PSA. Three were found to harbor prostate
      cancer and have undergone therapy. The remaining 65 patients continue on
      surveillance. PSAD can predict treatment outcomes for patients with clinically
      localized prostate cancer treated with radical prostatectomy. PSADs at low values
      are 90% accurate in predicting operative success. PSADs at high values are 67%
      accurate in predicting failure. Cancer 1994; 74: 1667-73.

PMID- 7521784
TI  - Comparative clinical efficacy and safety of immediate release and controlled
      release hydromorphone for chronic severe cancer pain.
AB  - BACKGROUND: The short elimination half-life of hydromorphone necessitates 4
      hourly dosing to maintain optimal levels of analgesia in patients with chronic
      cancer pain. The purpose of this study was to compare the clinical efficacy and
      safety of controlled release hydromorphone administered every 12 hours and
      immediate release hydromorphone administered every 4 hours in patients with
      chronic severe cancer pain. METHODS: Forty-eight patients with stable chronic
      severe cancer pain were randomized, in a double-masked crossover study, to
      controlled release hydromorphone every 12 hours or immediate release
      hydromorphone every 4 hours for 7 days each. Pain intensity was assessed using a
      visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain
      Questionnaire. Nausea and sedation were also assessed using a VAS. Assessments
      were made by the patient four times a day at 7:00 a.m., 11:00 a.m., 3:00 p.m.,
      and 7:00 p.m. Use of rescue hydromorphone also was recorded by the patient.
      RESULTS: Forty-five patients completed the study (26 women, 19 men; mean age,
      57.1 +/- 13.6 years) and received a mean daily dose of 76 +/- 133 mg (range, 6
      768 mg). There were no significant differences between controlled release
      hydromorphone and immediate release hydromorphone in overall VAS pain intensity
      scores (19 +/- 14 vs. 20 +/- 14 mm), ordinal pain intensity scores (1.2 +/- 0.8
      vs. 1.2 +/- 0.8) and pain scores by day of treatment or time of day. The daily
      rescue analgesic consumption during controlled release hydromorphone and
      immediate release hydromorphone did not differ significantly overall (1.1 +/- 1.1
      vs. 1.0 +/- 1.1 doses per day) or with respect to time of day. There were no
      significant differences in overall VAS sedation scores (18 +/- 18 mm vs. 19 +/-
      18 mm) and in overall mean VAS nausea scores (12 +/- 15 mm vs. 11 +/- 14 mm)
      between controlled release hydromorphone and immediate release hydromorphone.
      CONCLUSIONS: Controlled release hydromorphone administered every 12 hours is as
      effective as immediate release hydromorphone administered every 4 hours in the
      management of patients with chronic severe cancer pain. The benefits of
      controlled release hydromorphone lie in the convenience of its capsule
      formulation, which can be sprinkled on soft food, and its 12-hour duration of
      action, which allows patients uninterrupted sleep and improved compliance.

PMID- 7521785
TI  - Changes in Tc-99m radionuclide bone scan images and peripheralization of marrow
      hematopoietic activity associated with the administration of granulocyte colony
      stimulating factor as an adjunct to dose-intensified chemotherapy for breast
      cancer. A case report.
AB  - Granulocyte colony stimulating factor (G-CSF) is used clinically for chemotherapy
      associated neutropenia. Very little is known about the manner in which
      pharmacologic dosing of G-CSF may affect radiologic studies in vivo. Dramatic
      changes on bone scan associated with the administration of G-CSF used to support
      dose-intensified combination chemotherapy in a patient with metastatic breast
      carcinoma are described. The scintigraphic findings were correlated
      histologically with increased hematopoietic activity in the bone marrow located
      in peripheral bones.

PMID- 7521780
TI  - Intracellular labeling of cat spinal neurons using a tetramethylrhodamine-dextran
      amine conjugate.
AB  - Tetramethylrhodamine-dextran is a highly fluorescent neuroanatomical tracer that,
      in its 10,000 MW form, has seen widespread use as a sensitive anterograde tract
      tracing label. We report here the use of a lower molecular weight
      tetramethylrhodamine-dextran (3000 MW; Molecular Probes, OR) as an in vivo
      intracellular marker of locomotor-related spinal neurons. In the paralyzed,
      decerebrate cat preparation, fictive locomotion was evoked by electrical
      stimulation of the mesencephalic locomotor region. Extracellular and
      intracellular potentials of rhythmically active spinal neurons were recorded
      using microelectrodes filled with 2% tetramethylrhodamine-dextran (3000 MW) in
      0.9% saline (impedance 5-20 Mohm). Following impalement and electrophysiological
      characterization, neurons were iontophoretically injected for 2-30 min with 3-10
      nA of pulsed positive current. Animals were then perfused 30 min to 7 h
      postinjection with a variety of paraformaldehyde- and glutaraldehyde-containing
      fixatives. After tissue sectioning, more than 90% of the injected neurons were
      recovered. Choline acetyltransferase-immunoreactivity could be demonstrated in a
      subpopulation of tetramethylrhodamine-dextran-labeled neurons. This technique, in
      addition to producing high-quality electrodes, has the advantages of rapid yet
      extensive filling of neuronal processes, no tissue processing prior to
      visualization, and compatibility with immunohistochemistry.

PMID- 7521787
TI  - Correlation between the bromodeoxyuridine labeling index and the MIB-1 and Ki-67
      proliferating cell indices in cerebral gliomas.
AB  - BACKGROUND: Recently, it has been shown that heating paraffin embedded tumor
      sections in a microwave oven can reactivate an epitope of Ki-67 protein that is
      recognized by the monoclonal antibody MIB-1. With this technique, a close
      correlation was shown between the bromodeoxyuridine labeling index (BUdR LI) and
      the MIB-1 proliferating cell index (PCI) in corresponding regions of
      glioblastomas. METHODS: The reliability of the MIB-1 PCI as a marker of
      proliferation was evaluated in 90 cerebral gliomas. The MIB-1 immunostaining of
      ethanol-fixed, paraffin embedded sections of 23 moderately anaplastic
      astrocytomas, 22 highly anaplastic astrocytomas, 30 glioblastomas, and 15 mixed
      malignant gliomas was compared with the BUdR LI and, in some cases, the Ki-67
      PCI. RESULTS: MIB-1 positive cells were detected easily in the majority of the
      cases, and the MIB-1 immunostaining was often superior to that of Ki-67 in
      individual tumors. The MIB-1 PCI was significantly higher than the Ki-67 PCI and
      the BUdR LI. Linear-regression analysis showed significant correlations among the
      three indices. The MIB-1 PCI was correlated with the BUdR LI in each group of the
      astrocytic tumors and mixed malignant gliomas; the MIB-1 PCI was approximately
      2.4-2.8 times higher than the BUdR LI. CONCLUSIONS: The close correlation between
      the MIB-1 PCI and the in vivo BUdR LI in serial sections of glioma subtypes
      suggests that MIB-1 immunostaining is a useful technique for analyzing the
      proliferative potential of individual gliomas.

PMID- 7521786
TI  - In vitro modulation of the invasive and metastatic potentials of human renal cell
      carcinoma by interleukin-2 and/or interferon-alpha gene transfer.
AB  - BACKGROUND: Continuous local delivery of interleukin-2 (IL-2) and interferon
      alpha (IFN-alpha) via gene transfer appears to be more effective than systemic
      therapy in preventing the growth of human renal cell carcinoma (RCC) in vitro and
      in vivo. To understand further if cytokine-gene transfection of RCC could alter
      certain cellular properties that are associated with the invasive and metastatic
      potentials of tumor, the authors characterized six cell lines that produce IL-2
      and/or IFN-alpha in their expression of intercellular adhesion molecule-1 (ICAM
      1) and CD44; binding affinity to extracellular matrix (ECM) components
      (fibronectin, laminin, type IV collagen, and vitronectin); and preference in
      forming homotypic aggregation and mRNA levels of c-myc, epidermal growth factor
      receptor (EGF-R), tumor transforming growth factor-beta (TGF-beta) and type IV
      collagenase. These six lines were compared with control vector transfected
      parental R11 line. METHODS: The expression of ICAM-1 and CD44 was determined by
      fluorescence-activated cell sorter (FACS) analysis, the tumor cell binding
      affinity to ECM components was measured by cell attachment assay, the degree of
      homotypic aggregation was quantified by cell aggregation assay, and the mRNA
      levels of c-myc, EGF-R, TGF-beta, and collagenase were analyzed by a quantitative
      polymerase chain reaction analysis. RESULTS: Both IL-2-gene- and IFN-alpha-gene
      modified R11 exhibited enhanced expression of ICAM-1, suppression of CD44, and
      decreased binding affinity to ECM components, when compared with the R11-control
      vector. All cytokine-producing tumor lines showed a decreased preference to form
      homotypic aggregation. Interferon-alpha gene transfer downregulated c-myc, EGF-R,
      and type IV collagenase mRNA expression, whereas only the higher producers of IL
      2 downregulated TGF-beta mRNA expression. Exogenous IL-2 and/or IFN-alpha
      treatment of a IFN-alpha-resistant RCC enhanced both HLA class I antigen and ICAM
      1 expression and suppressed CD44 expression, but had no effect on tumor growth
      rate. CONCLUSIONS: The local production of high concentrations of IL-2 and IFN-a
      at the tumor site may directly alter tumor properties associated with invasive
      and metastatic phenotypes of RCC. Interleukin-2 and/or IFN-alpha gene therapy may
      be an effective strategy for treatment of patients with advanced renal cancer.

PMID- 7521789
TI  - [Hepatitis C antibodies (anti-HCV) in blood donors at the transfusion department
      in Brno].
AB  - BACKGROUND: The hepatitis C virus is considered the main cause of post
      transfusion non-A, non-B hepatitis and the persistence of anti-HCV antibody is
      considered a sign of chronic disease. The objective was to assess the incidence
      of anti-HCV positivity in blood donors of the blood transfusion department in
      Brno where sera of donors of a major part of the South Moravian region are
      examined. METHODS AND RESULTS: The authors examined between April 1, 1992 and
      Jan. 31, 1993 27,559 sera of blood donors for anti-HCV, using a MONOLISA anti-HCV
      set of Diagnostics Pasteur Co. The sera were divided into donors who gave blood
      for the first time and steady donors. Sera collected during the first three
      months (April 1, 1992 to June 30, 1992) were excluded as anti-HCV was not
      assessed before that date. In each group the percentage of sera was assessed
      where repeatedly reactivity to anti-HCV was recorded. In the whole group of
      examined sera repeated reactivity to anti-HCV was found in 0.243%. In those who
      were blood donors for the first time it was 0.408%, in repeated donors 0.210%. In
      first donors anti-HCV positivity was present in 0.334% during the first three
      months and 0.443% during the remaining 7 months. A very similar incidence was
      found also in steady donors--0.349% during the first three months, as before
      April 1, 1992 these donors were not yet excluded from blood donorship on account
      of anti-HCV positivity. In steady donors during the last 7 months a marked drop
      of anti-HCV positivity to 0.150% was found due to exclusion of anti-HCV positive
      subjects during the previous three months. CONCLUSIONS: In blood donors from the
      South Moravian region positivity of anti-HCV antibodies was recorded 0.35% to
      0.44%.

PMID- 7521788
TI  - Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and
      prednisolone using recombinant human granulocyte colony stimulating factor in non
      Hodgkin's lymphoma.
AB  - BACKGROUND: Several uncontrolled trials have suggested that dose intensity of
      chemotherapy is a crucial determinant of treatment outcome for patients with non
      Hodgkin's lymphoma (NHL). To explore the possibility of increasing dose
      intensity, a dose-escalation study of cyclophosphamide, doxorubicin, vincristine,
      and prednisolone (CHOP) using recombinant human granulocyte colony stimulating
      factor (rhG-CSF) was initiated. METHODS: First, the feasibility of standard dose
      CHOP (750 mg/m2 cyclophosphamide intravenously [i.v.] on Day 1;50 mg/m2
      doxorubicin i.v. on Day 1; 1.4 mg/m2 vincristine i.v. on Day 1; and 100 mg/body
      prednisolone orally on Days 1-5) repeated biweekly at the original dose was
      assessed. rhG-CSF was given subcutaneously at doses of 2-5 micrograms/kg every
      day or every other day on Days 3-13. The safety of increasing the dose of
      cyclophosphamide during biweekly CHOP then was tested. Besides the standard dose
      (750 mg/m2), two dose levels of cyclophosphamide were set (1200 mg/m2 and 1500
      mg/m2 in patients younger than 61 years of age, and 1200 mg/m2 in patients 61-75
      years old). RESULTS: Twenty-seven patients with NHL who had received minimal or
      no previous treatment were enrolled in this study. In the 750 mg/m2 group, 9
      patients received 3-6 cycles of treatment (mean, 3.9 cycles), in the 1200 mg/m2
      group, 10 patients received 3-6 cycles (mean, 4.8), and in the 1500 mg/m2 group,
      all 8 patients received 6 cycles. No significant differences among the groups
      were observed in the extent and the duration of neutropenia in each cycle, and a
      leukocyte count of more than 3000/microliters on Day 15 was achieved in all 131
      cycles. Hemoglobin values and platelet counts, however, decreased in the later
      cycles in the 1500 mg/m2 group. Two patients were hepatitis-B virus carriers, one
      of whom died of fulminant hepatitis after completion of six cycles. Another
      patient developed a transient increase of transaminases after the second cycle.
      One other patient developed Grade 4 mucositis (World Health Organization scale).
      The numbers of patients who achieved complete and partial responses,
      respectively, were 4 (50%) and 2 (25%) in the 750 mg/m2 group, 8 (80%) and 2
      (20%) in the 1200 mg/m2 group, and 8 (100%) and 0 (0%) in the 1500 mg/m2 group.
      CONCLUSIONS: The dose of cyclophosphamide in biweekly CHOP can be increased up to
      1500 mg/m2 with no increase in the incidence of treatment-related early
      mortalities without any organ damage in younger patients. The efficacy of this
      dose intensification of CHOP currently is being investigated in a multicenter
      prospective randomized trial using three different dose levels of
      cyclophosphamide.

PMID- 7521790
TI  - Nerve fibers immunoreactive for substance P and calcitonin gene-related peptide
      in the cervical spinal ventral roots of the mouse.
AB  - We demonstrate the existence of nerve fibers possessing substance P (SP) and
      calcitonin gene-related peptide (CGRP) immunoreactivity in the mouse cervical
      ventral roots. The distribution of the SP and CGRP fibers was similar, but CGRP
      fibers were generally more numerous. Both types entered the ventral pia mater or
      formed hairpin loops, but they did not enter the spinal cord directly through
      these roots. SP and CGRP fibers in the ventral roots were thin and had many
      varicosities. We suggest that these SP and CGRP fibers are involved not only in a
      sensory mechanism, but also in other functions, via the release of SP and CGRP
      from varicosities in the ventral roots.

PMID- 7521791
TI  - Chemically defined collateral projections from the pons to the central nucleus of
      the amygdala and hypothalamic paraventricular nucleus in the rat.
AB  - Triple fluorescence labelling was employed to reveal the distribution of
      chemically identified neurons within the pontine laterodorsal tegmental nucleus
      and dorsal raphe nucleus which supply branching collateral input to the central
      nucleus of the amygdala and hypothalamic paraventricular nucleus. The chemical
      identity of neurons in the laterodorsal tegmental nucleus was revealed by
      immunocytochemical detection of choline-acetyltransferase or substance P; in the
      dorsal raphe nucleus, the chemical content of the neurons was revealed with
      antibody recognizing serotonin. The projections were defined by injections of two
      retrograde tracers, rhodamine- and fluorescein-labelled latex microspheres, in
      the central nucleus of the amygdala and paraventricular nucleus, respectively.
      Neurons projecting to both the central nucleus of the amygdala and the
      paraventricular nucleus were distributed primarily within the caudal extensions
      of the laterodorsal tegmental nucleus and dorsal raphe nucleus. Approximately 11%
      and 7% of the labelled cells in the laterodorsal tegmental nucleus and dorsal
      raphe nucleus projected via branching collaterals to the paraventricular nucleus
      and central nucleus of the amygdala. About half of these neurons in the
      laterodorsal tegmental nucleus were cholinergic, and one-third were substance-P
      ergic; in the dorsal raphe nucleus, approximately half of the neurons containing
      both retrograde tracers were serotonergic. These results indicate that pontine
      neurons may simultaneously transmit signals to the central nucleus of the
      amygdala and paraventricular nucleus and that several different neuroactive
      substances are found in the neurons participating in these pathways. This
      coordinated signalling may lead to synchronized responses of the central nucleus
      of the amygdala and paraventricular nucleus for the maintenance of
      homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521795
TI  - [Serological investigation on intrafamilial transmission of HCV infection].
AB  - To clarify the intrafamilial transmission of HCV infection, the antibody to HCV
      was assayed in 124 serum samples from the family members of 60 HCV-Ab (+) index
      cases (group C), and compared with that from 83 family members of 40 HCV-Ab (-)
      index patients with hepatitis B (group B), Nine of 124, including 2 parents, 6
      spouse and 1 granddaughter, were positive for anti-HCV. The prevalence of anti
      HCV was 7.3% (9/124) in total, and 1.85% (2/108) in the subjects who had no
      history of blood donation. None of 83 was positive for anti-HCV in group B. On
      the other hand, the prevalence of HBV infection was 25.33% in the group of HCV
      infection only, and 40.91% in the group with HBV/HCV double-infection or HBV
      infection. It indicates that the risk of HBV intrafamilial transmission is higher
      than that of HCV, and the risk of transmission of HCV from mother to infant may
      be lower than that of sexual transmission.

PMID- 7521792
TI  - The distribution and origin of nerve fibers immunoreactive for substance P and
      neurokinin A in the anterior buccal gland of the rat.
AB  - The distribution and origin of substance P (SP) and neurokinin A (NKA) were
      studied in rat in the anterior buccal glands, which are minor mucous salivary
      glands. Indirect immunofluorescence staining showed moderate SP and NKA
      innervation of salivary acini and interlobular ducts, whereas blood vessels were
      more sparsely innervated, and there were few nerve fibers in the stroma and
      around the intralobular ducts. About 10%-20% of the trigeminal ganglion cells
      showed equally strong immunoreactivity to both SP and NKA. Unilateral denervation
      of the branches of the trigeminal nerve caused complete disappearance of the
      stromal fibers and greatly reduced the number of all other SP-immunoreactive and
      NKA-immunoreactive nerve fibers. In the superior cervical ganglia, SP and NKA
      immunoreactivity was restricted to small intensely fluorescent cells; SP and NKA
      immunoreactivity was absent from principal ganglionic cells, and thus
      sympathectomy had no any effect on the number or distribution of fibers
      immunoreactive for SP and NKA in the anterior buccal glands. The fibers remaining
      after sensory denervation could have been of parasympathetic origin, indicating a
      dual origin of nerves immunoreactive for SP and NKA in these glands. The present
      data demonstrate that the major part of the glandular SP and NKA innervation in
      the minor salivary glands derives from the trigeminal ganglia. The distribution
      of the peripheral nerve fibers indicates that they may play a role in the
      delivery of potent neuropeptides involved in the vascular, secretory, and motor
      (myoepithelial cells) functions of salivary glands.

PMID- 7521793
TI  - Effects of illumination and enucleation on substance-P-immunoreactive structures
      in subcortical visual centers of golden hamster and Wistar rat.
AB  - The undecapeptide substance P is found in different entities of the visual system
      that control eye movement and synchronize endogenous rhythms with the light cycle
      (i.e., superior colliculus, suprachiasmatic nucleus, intergeniculate leaflet).
      Immunocytochemical methods were used to compare the reactivity to substance P in
      the brain of five groups of golden hamsters and two groups of Wistar rats: (1)
      untreated hamsters kept under 14L:10D and sacrificed at noon; (2) identically
      maintained animals sacrificed at midnight; (3) enucleated animals kept under
      control conditions; (4) hamsters kept under constant darkness; (5) hamsters kept
      under the same conditions as the controls, but intraventricularly injected with
      colchicine. The results obtained in golden hamsters of groups (1) and (3) were
      compared with findings in Wistar rats treated accordingly [groups (6) and (7)].
      Substance P-immunoreactive perikarya were found in the suprachiasmatic nucleus
      and superior colliculus of hamsters and Wistar rats. Substance P-immunoreactive
      nerve fibers were abundant in the hypothalamic area ventral to the
      paraventricular nucleus, in the intergeniculate leaflet, in some thalamic nuclei,
      and in the superior colliculus. Immunoreactivity to substance P in the
      suprachiasmatic nucleus and intergeniculate leaflet did not vary among the
      experimental groups. However, a conspicuous decrease in reactivity to substance P
      was observed in the superficial layers of the superior colliculus of enucleated
      hamsters and rats, compared with all other groups. These results indicate that
      substance P immunoreactivity in the superior colliculus, but not that in the
      suprachiasmatic nucleus or intergeniculate leaflet, depends on the integrity of
      the retinal projection.

PMID- 7521794
TI  - Morphological changes during fiber type transitions in low-frequency-stimulated
      rat fast-twitch muscle.
AB  - This study investigates morphological adaptations of rat extensor digitorum
      longus muscle to chronic low-frequency stimulation (10 Hz, 10 h/d, up to 61 +/-
      7d). During the early stimulation period (2-4 d), increased basophilia and
      accumulation of RNA were seen predominantly in type-IIB fibers. Putative
      satellite cell activation, as indicated by 3H-thymidine incorporation, was also
      evident during this phase. By 12 d, fiber composition remained unaltered, but
      there was a decrease in the cross-sectional area of the type-IIB fibers.
      Following 28 d of low-frequency stimulation, the percentage of type-IIB fibers
      decreased from 43 +/- 3% to 0%, while type-IID fibers increased from 30 +/- 3% to
      60 +/- 6%. The fraction of type-IIA fibers tended to increase (controls 19 +/-
      3%; stimulated 29 +/- 4%), whereas that of the type-I fibers was unaltered (4 +/-
      1%). At this time, the cross-sectional area of type-IID fibers was unaltered, but
      that of type-IIA and type-I fibers increased. Further stimulation resulted in a
      return of type-IID fibers to control levels (23 +/- 5%), and a marked increase in
      type-IIA fibers (45 +/- 8%). The percentage of type-I fibers increased from 4 +/-
      1% to 8 +/- 1%. Throughout each stage of chronic stimulation, there was no
      histological evidence of fiber degeneration and regeneration. These results
      indicate that, in contrast to the rabbit, chronic low-frequency stimulation
      induced fiber conversion in the rat extensor digitorum longus muscle is entirely
      due to fiber transformation.

PMID- 7521798
TI  - [The effect of IL-1 receptor antagonist on bleomycin-induced pulmonary fibrosis].
AB  - Interleukin-1 (IL-1) is a cytokine with diverse biological activities. It can
      serve as a fibroblast (FB) growth factor which involves in the development of
      pulmonary fibrosis. IL-1 receptor antagonist (IL-1ra) can compete with IL-1 for
      occupancy of surface receptors of target cells without agonist effect. In order
      to find a new method to treat pulmonary fibrosis, we investigated the effect of
      recombinant human IL-1ra on the development of pulmonary fibrosis by evaluating
      collagen content, histological change, and TGF-beta mRNA expression in the rats
      bleomycin-induced pulmonary fibrosis. The results indicate are that there are no
      significant difference between the IL-1ra treated group and the control group.

PMID- 7521796
TI  - Translation in a wheat germ cell-free system of RNA from mitochondria of the
      normal and Texas male-sterile cytoplasms of maize (Zea mays L.).
AB  - RNA isolated from etiolated seedling shoot mitochondria of maize (Zea mays L.)
      with normal (N) or Texas male-sterile (T) cytoplasm stimulated the incorporation
      of [35S]-methionine into protein when added to a cell-free protein-synthesizing
      system from wheat germ. Discrete polypeptides with molecular masses of up to
      approximately 67 kDa were synthesized, and the pattern of bands was distinct from
      that obtained with total RNA. Products of translation of T-urf13 RNA were
      identified by immunoprecipitation, and of atpA, coxI, and coxII RNA by hybrid
      arrest of translation by the cloned gene. Several polypeptides were
      differentially synthesized from N and T mitochondrial RNA; these differences were
      more extensive than those found when isolated, intact, N and T mitochondria are
      allowed to synthesize proteins.

PMID- 7521799
TI  - [Dynamic changes in extracellular matrix and related interstitial cells in
      experimental organ sclerosis].
AB  - The dynamic changes of extracellular matrix (ECM) and effected interstitial cells
      in experimental sclerosis (fibrosis) of the liver, lung and kidney glomeruli of
      rats were studied by immunohistochemical methods with monospecific antibodies
      against fibronectin, laminin, collagen type I, III, IV, V, desmin, vimentin and
      alpha-smooth muscle actin. The results suggest that there exists an organ
      (tissue) sclerosis effective cell system involved in ECM synthesis. The
      activation usually initiates from the Ito cell (liver), primitive mesenchymal
      call (lung), and mesangial cell (glomeruli), sometimes followed by fibroblast and
      myofibroblast differentiation with the transformation of cytoskeleton expression.
      Desmin is the most sensitive marker to reflect the functional state of the organ
      sclerosis effective cell system from the resting to the activating state.

PMID- 7521801
TI  - [The immune response evokes changes of substance P content in some brain areas].
AB  - The neuroimmunomodulation (NIM) function of substance P (SP) in some brain areas
      of rats was investigated by the hemolytic plaque-forming cell (PFC) technique for
      detecting humoral immune function, and by radioimmunoassay for assessing SP
      content in some brain areas. The results showed that the contents of SP in the
      hypothalamus, hippocampus and pons were significantly decreased, while SP
      contents in the hypophysis, midbrain and medulla were not significantly changed
      at the peak of the immune response to sheep red blood cells (SRBC).
      Intracerebroventricular injection of capsaicin and SP antiserum had no effect on
      the immune response to SRBC. These results suggest that the immune response could
      affect the metabolism of SP in some brain areas, and provide further evidence
      that the nervous system (NS) can both regulate immune function and be affected by
      it.

PMID- 7521797
TI  - Suppression of a mitochondrial point mutation in a tRNA gene can cast light on
      the mechanisms of 3' end-processing.
AB  - We used a genetic approach to study the nuclear factors involved in the
      biogenesis of mitochondrial tRNAs. A point mutation in the mitochondrial
      tRNA(Asp) gene of Saccharomyces cerevisiae had previously been shown to result in
      a temperature-sensitive respiratory-deficient phenotype as a result of the
      absence of 3' end-processing of the tRNA(Asp). Analysis of mitochondrial
      revertants has shown that all revertants sequenced have a G-A compensatory change
      at position 53, which restores the hydrogen-bond with the mutated nucleotide. We
      then searched for nuclear suppressors to identify the nuclear gene(s) involved in
      mitochondrial tRNA 3' end-processing. One such suppressor mutation was further
      characterized: it restores tRNA(Asp) maturation and growth at 36 degrees C on
      glycerol medium in heterozygous diploids, but leads to a defective growth
      phenotype in haploids.

PMID- 7521800
TI  - [The relationship between thymus involution and diseases in childhood].
AB  - 70 thymuses obtained at autopsy from children who died of various diseases were
      studied with histological, immunohistochemical and ultrastructural methods. In
      the immunohistochemical study, antibodies against 8 lymphocyte differentiation
      antigens, including CD4, CD8, CD3, CD1, CD2, CD25, CD22 and T9 as well as those
      against keration and S-100 protein were used. The findings suggest that thymus
      involution can occur in different diseases. The differentiation process of
      thymocytes and the distribution of different sub-populations of T cells in the
      thymus are not changed by thymus involution. Among the major changes of thymus
      involution, the decrease in number of dendritic cells and the degeneration of
      epithelial cells are more important than the decrease in the number of
      thymocytes. Phagocytosis of macrophages seems to be the secondary way to dispose
      of the degenerated and dead thymocytes.

PMID- 7521802
TI  - [Genomic cloning of Fasciola hepatica secretory antigens in Escherichia coli].
AB  - This paper reported the immunoscreening of three recombinants expressing
      secretory antigens from the genomic DNA library of F. hepatica and the primary
      study of expression of the three recombinants. To construct the genomic DNA
      library, DNA from the adult F. hepatica was cut with Sau3AI to an average length
      of about 2.0 kb and inserted into the BamHI site of the expression vector pUC18,
      the size of the genomic DNA library of F. hepatica being 1.5 x 10(5)
      recombinants. Three recombinants expressing antigenic determinants of F. hepatica
      pFH16, pFH23, pFH48 were detected through primary screening and rescreening with
      F. hepatica infected rabbit serum (1:50) preabsorbed to remove antibodies to E.
      coli and SPA-HRP (1:40). The test of the ability of expressing fusion proteins
      showed pFH16 > pFH48 > pFH23. These studies provide the possibility of further
      research on the expression of recombinant antigenic genes, the immunity of their
      expressed products and the protection of animals.

PMID- 7521804
TI  - [Comparative studies on the diagnosis of clonorchiasis by IEST and IFAT].
AB  - Both immunoenzymatic staining technique (IEST) and indirect fluorescent antibody
      test. (IFAT) with frozen sections of adult Clonorchis sinensis as antigen were
      employed for detecting 51 cases with clonorchiasis and 50 healthy persons. The
      positive rate was 92% with IEST and 88% with IFAT. The results showed no
      significant statistic difference (P > 0.05). The false positive rates were 2%
      with the former and 4% with the latter. When sera from 22 cases with acute
      schistosomiasis, 20 cases with chronic schistosomiasis and 15 cases with
      paragonimiasis were examined by IEST and IFAT, cross-reactions were 14%, 5% and
      0% with IEST, and 14%, 10% and 0% with IFAT, respectively. The results showed
      that both IEST and IFAT are useful methods for serological diagnosis of
      clonorchiasis and the antigen on the gut was well demonstrated, while IEST might
      be more suitable in field surveys.

PMID- 7521803
TI  - [Studies on immunoenzymatic staining technique using ultrasonicated dry egg
      section on PVC membrane for diagnosis of schistosomiasis japonica].
AB  - Immunoenzymatic staining technique (IEST) using PVC-membrane coated with
      Schistosoma japonicum ultrasonicated dry egg (UDE) and liver egg PVC-IEST was
      carried out to detect specific antibodies in sera from 159 cases with
      schistosomiasis japonica, the positive rates being 98.1% (156/159) and 97.5%
      (155/159), respectively. The sera from 63 healthy individuals showed false
      positive reaction in 2 cases and 1 case, respectively, suggesting that the
      sensitivity and specificity of the two tests were similar. However, the positive
      intensity was higher in UDE section than in liver egg section (P > 0.05). As the
      UDE section could be stained more obvious and the PVC membranes are cheap and
      could be easily brought so that this method might be applicable for practical
      purposes.

PMID- 7521805
TI  - [The correlation between postsynaptic inhibition and GABA, opioid peptides, SP in
      electroacupuncture].
AB  - Identified tract cells in lumbar enlargement were recorded from intact
      anaesthetized rats. The prolongation of the latency of antidromic action
      potential was a measure of postsynaptic inhibition. Both ST 36 and SP 6 were
      stimulated electrically. In EA group (N = 12) EA prolonged the latency for 0.111
      +/- 0.022 ms (P < 0.001). In bicuculline group (N = 12) the prolongation of the
      latency for 0.010 +/- 0.004 ms (P < 0.05) by EA was less than that of EA group
      with statistical significance. In naloxone group (N = 12) and SP antiserum group
      (N = 12) EA did not induce a significant prolongation of the latency. It
      suggested that GABA, opioides and SP might be involved in postsynaptic inhibition
      induced by EA.

PMID- 7521807
TI  - Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease
      exacerbations in patients with systemic lupus erythematosus (SLE); a long term
      prospective study.
AB  - Active SLE is characterized by immune deposits and subsequent vascular
      inflammation in many organs. Expression and up-regulation of adhesion molecules
      is basic to migration of inflammatory cells into the tissues. Recently, soluble
      isoforms of these molecules have been described which might be an expression of
      their up-regulation in the tissues and, as such, of disease activity. The purpose
      of this study was to evaluate whether changes in levels of soluble adhesion
      molecules reflect disease activity. We analysed serial sera in a 6-month period
      preceding 22 consecutive exacerbations of SLE for levels of soluble vascular cell
      adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM
      1), and sE-selectin. Levels were related to clinical disease activity (SLEDAI),
      and levels of anti-dsDNA and complement. At the time of maximal disease activity,
      levels of sVCAM-1 in patients with SLE were higher than those in controls (P <
      0.0001), levels in patients with renal involvement being higher than in those
      without (P < 0.02). Levels of sVCAM-1 correlated with SLEDAI scores (P < 0.05)
      and, inversely, with levels of C3 (P = 0.01). In addition, in the presence of
      anti-dsDNA, levels of sVCAM-1 tended to correlate with levels of these
      autoantibodies (P < 0.1). Levels of sICAM-1 were normal and sE-selectin levels
      even decreased compared with controls. Levels of sVCAM-1 were higher at the
      moment of relapse (P = 0.001) than at 6 months before this time point. This rise
      correlated with the rise in SLEDAI score (P < 0.02). Levels of sICAM-1 and sE
      selectin did not rise, and remained in the normal range in all exacerbations
      studied. In conclusion, in contrast to sICAM-1 and sE-selectin, levels of sVCAM-1
      are increased, rise parallel to disease activity during exacerbations in SLE, and
      are associated with decreasing levels of complement factors. This favours the
      hypothesis of immune deposit formation, activation of the complement cascade and
      activation of endothelial cells. Concurrent up-regulation of vascular adhesion
      molecules may thus result in transmigration of activated inflammatory cells
      inducing tissue damage.

PMID- 7521806
TI  - Multispecific and heterogeneous recognition of the gag protein by cytotoxic T
      lymphocytes (CTL) from HIV-infected patients: factors other than the MHC control
      the epitopic specificities.
AB  - The HIV gag polyprotein is a major target for recognition by CTL in infected
      humans. Using recombinant vaccinia viruses (rVV) expressing truncations of the
      p24gag, and the p18gag, p15gag and HIV-2 p56gag proteins, the characterization of
      epitope regions recognized by in vitro-stimulated peripheral blood mononuclear
      cells (PBMC) from 18 infected patients has been studied. The gag-specific
      response of most individuals is polyclonal and multispecific, and interindividual
      variations between target epitope regions were frequently observed, despite
      shared MHC alleles. As CTL may play an important role in the control of HIV
      replication in infected hosts, these results have important implications for
      designing vaccine strategies.

PMID- 7521809
TI  - Increase in the proportion of granulated CD56+ T cells in patients with
      malignancy.
AB  - Evidence is presented for the existence of a unique T cell population which
      expressed one of the natural killer (NK) markers, CD56 antigen, in humans.
      Although such CD56+ T cells were a minor population in the peripheral blood (<
      10%), they were abundant in the liver (up to 50%), which was recently
      demonstrated to be a major organ for extrathymic T cell differentiation in mice.
      As in the case of extrathymic T cells in mice, these CD56+ T cells in humans
      contained a higher proportion of gamma delta T cells than did CD56- T cells,
      contained double-negative CD4-8- cells, and had the morphology of large granular
      lymphocytes. This unique population of CD56+ T cells tended to be elevated in the
      blood and among tumour-infiltrating lymphocytes in patients with colorectal
      cancer, especially in advanced cases. These results raise the possibility that,
      as in mice, CD56+ T cells with extrathymic T cell properties may also be
      associated with tumour immunity in humans.

PMID- 7521810
TI  - The return of the repressed: bringing culture back to psychiatry.

PMID- 7521808
TI  - Expression of the chemokine superfamily in rheumatoid arthritis.
AB  - The infiltration of leucocytes into the joint of rheumatoid arthritis (RA) is
      believed to be mediated by chemotactic factors released by activated cells. In
      this study, examination was made of the gene expression and production of the
      chemokine superfamily in RA patients by reverse transcriptase-polymerase chain
      reaction (RT-PCR) and immunoprecipitation. Cultured synovial fibroblasts were
      found capable of expressing and producing IL-8, GRO, monocyte chemotactic and
      activating factor (MCAF), macrophage inflammatory protein-1 alpha (MIP-1 alpha),
      MIP-1 beta and RANTES in response to IL-1 alpha. The expression of IL-8, GRO,
      MCAF, MIP-1 alpha, and MIP-1 beta was clearly shown to increase in freshly
      isolated synovial fluid mononuclear cells (SFMC) of RA patients, in contrast to
      peripheral blood mononuclear cells (PBMC) of RA patients and normal subjects. The
      gene expression of RANTES appeared to be the same for RA SFMC, RA PBMC, and
      normal PBMC. Thus, the over-expression of various chemokines may promote the
      recruitment of inflammatory cells into rheumatoid inflamed joints.

PMID- 7521811
TI  - The president's illness: culture, politics, and fetishism in Benin.

PMID- 7521812
TI  - Lip closing pressure in disabled children: a comparison with normal children.
AB  - Lip functions play an important role in the oral stages of feeding. Lip closing
      is an important early motor act in food acquisition and is essential for
      controlling chewing and swallowing. To date, there have been few papers on the
      developmental aspects of lip closing strength when taking in food, especially
      with regard to disabled children. This investigation was designed to produce an
      ordinal scale of midline lip pressure measurements for a cross-sectional, age
      grouped population of normal children. Developmental changes in lip pressure were
      then compared with those of two populations of disabled children. Pressure
      measurements were obtained with a strain gauge transducer that was embedded in a
      spoon during normal feeding. The study population consisted of 104 normal
      children ranging in age from 5 months to 5 years, 11 children who showed
      developmental delay (mean 4.5 years), and 10 children with cerebral palsy (mean
      5.0 years). Lip pressure was found to increase steadily from 5 months to 3 years
      and to increase slightly from 3 to 5 years in the normal population. The
      developmentally delayed group and the cerebral palsied group produced lip
      pressures and coefficients of variation below those of the normal 1 to 2-year-old
      group.

PMID- 7521813
TI  - Factors affecting the yield of acid-fast sputum smears in patients with HIV and
      tuberculosis.
AB  - OBJECTIVE: To evaluate the sensitivity of acid-fast sputum smears in the
      diagnosis of pulmonary Mycobacterium tuberculosis (MTB). DESIGN: Retrospective
      chart and radiographic film review. SETTING: Department of Veterans Affairs
      Medical Center in New York City. PATIENTS: All patients with positive sputum
      cultures for MTB during 1989 to 1991, including 100 with HIV, and 76 without HIV
      infection. PARAMETERS: The likelihood of a positive acid-fast sputum smear,
      related to chest radiograph findings, CD4 cell counts, drug sensitivity, and the
      presence of disseminated disease. RESULTS: Overall, 60 percent of patients with
      HIV had positive acid-fast smears, compared with 57 percent of non-HIV-infected
      patients. A relative absence of cavitary infiltrates did not substantially reduce
      the frequency of acid-fast smears in patients with and without HIV. Patients with
      HIV and CD4 count < 50, 50 to 200, and > 200 had positive acid-fast smear rates
      of 58 percent, 60 percent, and 56 percent, respectively; HIV-infected patients
      with drug-resistant organisms had 65 percent positive smears. Smear positivity
      was 96 percent in patients with HIV infection and disseminated MTB, CONCLUSIONS:
      Positive acid-fast sputum smears in culture-proven MTB occur with similar
      frequency in patients with and without HIV. The absence of cavitary disease did
      not significantly reduce the frequency of positive acid-fast smears. For patients
      with HIV, the likelihood of a positive smear was also independent of CD4 cell
      counts and drug resistance. Patients with HIV and disseminated MTB had positive
      sputum smears in nearly all cases.

PMID- 7521815
TI  - Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results
      of a meta-analysis of the literature.
AB  - STUDY OBJECTIVE: To contribute to the current debate about the relative merits of
      meta-analysis of the literature (MAL) and of individual patients data (MAP).
      DESIGN: Identification of published randomized trials and extraction of essential
      results directly from the published reports. SETTING: Chemotherapy vs supportive
      care in advanced non-small-cell lung cancer. MEASUREMENTS AND RESULTS: Survival
      probability at 6 months after randomization, as estimated from the published
      survival curves, has been considered as the end-point of interest. Quality
      scoring of the studies has also been performed. Specific methodologic issues
      concerning the estimation of relevant quantities necessary for the MAL have been
      addressed. The estimated pooled odds ratio of death was 0.44, with 95 percent
      confidence interval of 0.32 to 0.59, thus significantly favoring chemotherapy,
      and it corresponds to an estimated increase in median survival from 3.9 months
      for best supportive care to 6.7 for chemotherapy. CONCLUSIONS: The results of our
      MAL, favoring chemotherapy, are in line with those of a MAP recently published.
      However, they have to be considered in the light of their actual clinical
      relevance and of the balance between quality of life, toxicity, and costs of
      chemotherapy and best supportive care.

PMID- 7521814
TI  - Esophageal carcinoma with airway invasion. Evolution and choices of therapy.
AB  - In order to define the evolution of airway invasion by esophageal cancer, we
      reviewed 53 patients presenting with (group A) or without (group B)
      tracheoesophageal fistulae. Patients in group A were treated by esophageal bypass
      (4), esophageal diversion (4), expectant therapy (4), or esophageal prosthesis
      (1). The median survival was 4 months. Group B patients were treated by
      esophageal resection (18), esophageal bypass (4), or radiation therapy (13),
      depending on the extent of local disease. Bronchoscopy was a valuable tool for
      predicting resectability. Surgical resection, when possible, yielded better
      palliation. There were 4 long-term survivors in group B.

PMID- 7521817
TI  - Hyalin degeneration. Present in heart infarction & implicated in pathogenesis of
      heart rupture.

PMID- 7521816
TI  - Melioidosis in a diabetic sailor.
AB  - Melioidosis was diagnosed in a diabetic sailor who presented with a history and
      chest radiograph that suggested tuberculosis. Melioidosis is a tropical disease
      with protean manifestations: from asymptomatic infection to chronic cavitary lung
      disease to overwhelming sepsis. The diagnosis is easily made, even in nonendemic
      areas when duly considered by the clinicians and microbiology laboratory.
      Ceftazidime has dramatically improved outcomes in hospitalized patients with
      severe melioidosis.

PMID- 7521819
TI  - To "B" (CD20) or not to "B".

PMID- 7521820
TI  - Nerve-mediated nitric oxide production by opossum lower esophageal sphincter.
AB  - Antagonists of nitric oxide synthesis inhibit nerve-induced hyperpolarization and
      relaxation of muscle from the opossum lower esophageal sphincter. These studies
      test the hypothesis that nitric oxide is released during stimulation of intrinsic
      esophageal nerves. The intrinsic nerves were stimulated with an electrical field
      (10-sec trains of 1-msec, 30-V pulses delivered at 10 Hz). Nitric oxide
      production was measured with a DASIBI model 2108 Chemiluminescence NO Analyzer.
      NG-Nitro-L-arginine, an inhibitor of NO synthase, antagonized nerve-induced
      relaxation the lower esophageal sphincter. Nerve stimulation increased NO
      production from 0.50 +/- 0.04 nmol/min/100 mg tissue to 0.87 +/- 0.07
      nmol/min/100 mg tissue (P < 0.01). NG-nitro-L-arginine inhibited both basal
      (0.030 +/- 0.09 nmol/min/100 mg tissue, P < 0.05 vs baseline) and stimulated
      (0.38 +/- 0.10 nmol/min/100 mg tissue, P < 0.01 vs stimulated). These studies
      support the hypothesis that nerve stimulation releases nitric oxide from the
      lower esophageal sphincter.

PMID- 7521818
TI  - Two color flow cytometric analysis of concomitant acute myeloid leukemia and
      chronic lymphocytic leukemia.
AB  - During evaluation for macrocytic anemia and thrombocytopenia, a 74-year-old
      female was found to have a leukocytosis with two apparent populations of
      malignant cells identified in her peripheral blood smear and bone marrow
      aspirate. Morphologic characteristics of the two cell types were unusual, and
      cytochemical assays yielded ambiguous results. Two-color flow cytometric analysis
      demonstrated two distinct cell populations with immunophenotyping patterns
      consistent with chronic lymphocytic leukemia (CD5+/CD20+) and acute myelocytic
      leukemia (CD33+/CD34+), detected concurrently. The concomitant appearance of CLL
      and AML has been reported only rarely. The use of two-color flow cytometry to
      differentiate the populations demonstrates the utility of this technology in
      resolving unusual hematological malignancies.

PMID- 7521822
TI  - Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in active
      inflammatory bowel disease.
AB  - Intercellular adhesion molecule (ICAM)-1 promotes the initial interaction between
      macrophages and T cells during immune activation. We have measured serum levels
      of soluble ICAM-1 (sICAM-1) by ELISA in 27 patients with ulcerative colitis (UC),
      31 with Crohn's disease (CD), and 29 healthy subjects. The median sICAM-1 serum
      concentration was significantly increased in inflammatory bowel disease (IBD)
      patients (355 ng/ml, range 195-855) compared to controls (245 ng/ml, 155-580) (P
      = 0.001). Variance analysis for trend showed that sICAM-1 levels were
      significantly higher in patients with active CD and UC, compared to those with
      inactive disease and controls (P = 0.00002). The concentration of sICAM-1 was
      higher in CD patients (365 ng/ml 230-470) compared to UC (300 ng/ml 195-855) (P =
      0.01). Furthermore, weak but significant correlations were found between serum
      levels of sICAM-1 and: soluble IL-2 receptors, orosomucoid, and C-reactive
      protein. It is suggested that increased circulating sICAM-1 levels may reflect
      increased adhesiveness and signal transmission across cells, probably as a result
      of shedding of the parent molecule during local cellular immunoresponses in vivo.

PMID- 7521823
TI  - IgM and IgA antibodies generated against hepatitis C virus core antigen in
      patients with acute and chronic HCV infection.
AB  - Antibody subclasses directed against the core protein (HCc) of hepatitis C virus
      (HCV) were measured in 27 patients with acute non-A, non-B (NANB) hepatitis, and
      99 patients with chronic HCV-associated liver disease. IgM, IgA, and IgG anti-HCc
      responses were observed in 11 (40.7%), 7 (25.9%), and 18 (67%) patients with
      acute NANB hepatitis, respectively. Twenty-four (24.2%) and 40 (40.4%) patients
      with chronic HCV infection also had detectable IgM and IgA, respectively. IgM
      anti-HCc inconsistently detected acute infection, and HCV ribonucleic acid (RNA)
      could be detected preceding the rise in anti-HCc antibodies in five consecutive
      patients with acute hepatitis. IgM anti-HCc also could not distinguish acute from
      chronic infection and did not correlate with histologic progression. However, the
      form of IgA present (polymeric vs monomeric) did discriminate acute from chronic
      infection and the IgA anti-HCc titer correlated with histologic evidence of liver
      disease in patients with chronic HCV infection.

PMID- 7521824
TI  - The care and fitting of Naka-Rushton functions to electroretinographic intensity
      response data.
AB  - We developed an automated system to estimate parameters of the Naka-Rushton
      function based on a heuristic model of the electroretinogram intensity-response
      series. Data from a population of patients with central retinal vein occlusion
      were used to examine the ability of the derived parameters to predict the
      development of neovascularization of the iris. The predictive performance of this
      automated system in central retinal vein occlusion is comparable to that of a
      human expert.

PMID- 7521821
TI  - Immunomodulator therapy in inflammatory bowel disease.
AB  - The introduction of immunomodulator therapy in the treatment of patients with
      inflammatory bowel disease (IBD) has provided an important tool in modifying the
      mucosal immune system thought to be important in the pathogenesis of IBD.
      Currently available immunomodulating agents include azathioprine, 6
      mercaptopurine, cyclosporin, and methotrexate. Recent clinical trials have
      demonstrated that these agents have an important therapeutic role in the
      treatment of patients who are either refractory or intolerant to traditional
      medical therapy. They are useful in the induction and maintenance of remission
      for both ulcerative colitis and Crohn's disease. However, these agents have
      significant toxicities and limited efficacy. In addition, potential risks of
      malignancy and infection limit their indiscriminate use. Thus, with the better
      understanding of the molecular basis of mucosal immunity, innovative immune
      modifying therapies, such as antagonists of cytokines and inhibitors of T-cell
      activation, are being developed. It is likely that these exciting developments
      will soon result in specific immune modulating therapy with improved efficacy and
      reduced toxicity in the treatment of patients with IBD.

PMID- 7521825
TI  - The role of metabolic activation in drug toxicity.

PMID- 7521827
TI  - Sepsis management and antiendotoxin therapy after nebacumab. A reappraisal.

PMID- 7521826
TI  - Tiapride. A review of its pharmacology and therapeutic potential in the
      management of alcohol dependence syndrome.
AB  - Tiapride, an atypical neuroleptic agent, is a selective dopamine D2-receptor
      antagonist with little propensity for causing catalepsy and sedation. It shows
      preferential activity at receptors previously sensitised to dopamine and those
      located extrastriatally. Tiapride demonstrates antidyskinetic activity reflecting
      antidopaminergic actions, and also anxiolytic activity mediated by mechanisms
      that are poorly understood. Unlike the benzodiazepines, tiapride does not affect
      vigilance and has a low potential for interaction with alcohol (ethanol), and
      possibly for abuse. Tiapride facilitates management of alcohol withdrawal, but
      its use in patients at risk of severe reactions in acute withdrawal should be
      accompanied by adjunct therapy for hallucinosis and seizures. Since it may prove
      difficult to identify such patients and there is also a small risk of neuroleptic
      malignant syndrome (particularly with parenteral administration), the usefulness
      of tiapride in this setting is likely to be limited. Nevertheless, relative
      freedom from the complications associated with benzodiazepine therapy suggest a
      possible role for the drug in the treatment of individuals suitable for alcohol
      detoxification as outpatients. Preliminary clinical studies in alcoholic patients
      following detoxification have shown that tiapride ameliorates psychological
      distress, improves abstinence, and reduces drinking behaviour, and in the short
      term facilitates reintegration within society. These benefits were associated
      with reduced consumption of health care resources. However, the potential risk of
      tardive dyskinesia at the dosage employed (300 mg/day) requires evaluation and
      necessitates medical supervision. Thus, with its lack of adverse effects on
      vigilance and low propensity for interaction with alcohol and possibly for abuse,
      tiapride will probably find particular use in the management of alcoholic
      patients suitable for detoxification in an outpatient setting; and, if initial
      findings are confirmed in large well-designed trials, in the short term (< or = 6
      months) therapy of reformed alcoholic patients under medical supervision.

PMID- 7521828
TI  - Histamine H2-receptor antagonists in peptic ulcer disease. Evidence for a
      prophylactic use.
AB  - The H2-receptor antagonists have undoubtably been successful in healing primary
      gastric and duodenal ulcers so there is a tendency to assume that they will be
      equally successful when used as prophylactic agents. When used to prevent
      gastroduodenal ulceration induced by nonsteroidal anti-inflammatory agents, they
      are unsuccessful in protecting against gastric damage, but reduce the incidence
      of duodenal ulceration. However, their effect on the incidence of serious
      complications remains unknown. In the prevention of stress ulceration and
      bleeding in intensive care units there is evidence of a beneficial effect of H2
      receptor antagonists, but other agents are also equally effective. In patients
      who present with haematemesis and melaena, there is little evidence to show that
      H2-receptor antagonists reduce rates of transfusion or surgical intervention, or
      decrease mortality.

PMID- 7521829
TI  - Quinolone antibacterials. An update of their pharmacology and therapeutic use.
AB  - Quinolones are a class of antibiotics structurally related to nalidixic acid.
      They exhibit bactericidal activity primarily by inhibiting bacterial DNA gyrase.
      The early quinolones had a limited spectrum of activity, low potency, high
      frequency of spontaneous bacterial resistance, low serum drug concentrations and
      short half-lives, which virtually restricted their use to urinary tract
      infection. The new fluorinated quinolones differ from their predecessors in their
      broad antibacterial spectrum, including both Gram-negative and Gram-positive
      aerobic, and facultative anaerobic bacteria as well as many Mycobacterium spp.,
      Chlamydia spp., Legionella spp. and Mycoplasma spp., in addition to many strains
      of bacteria that are multiresistant to beta-lactam antibiotics and
      aminoglycosides. They also exhibit high potency, a low incidence of resistance,
      high oral bioavailability, extensive tissue penetration, low protein binding and
      long elimination half-lives. They are generally well tolerated apart from some
      gastrointestinal disturbance and rashes, including photosensitive eruptions and a
      propensity to cause central nervous system excitation. Clinically important
      interactions include those with antacids, theophylline, fenbufen and warfarin.
      Potential toxic effects include cartilage damage, ocular toxicity, teratogenicity
      and impairment of spermatogenesis. The role of fluoroquinolones continues to
      widen, encompassing infections of the urinary tract, respiratory tract, skin and
      soft tissues, bone and joints, infections in immunocompromised patients, sexually
      transmitted diseases, infectious diarrhoea, gynaecological infections and
      surgical prophylaxis. The convenience of oral therapy is an added advantage of
      the new fluoroquinolones.

PMID- 7521830
TI  - Parenteral aminoglycoside therapy. Selection, administration and monitoring.
AB  - Aminoglycosides are potent water-soluble antibiotics, with peak concentration
      dependent bactericidal activity against many pathogenic aerobic Gram-negative
      bacilli and Staphylococcus aureus. For systemic therapy, they must be given
      parenterally (intravenously or intramuscularly). In the body they remain largely
      extracellular, but penetration into cerebrospinal fluid and other secretions is
      meagre. They display trough concentration-dependent reversible nephrotoxicity and
      The commonly irreversible ototoxicity, which may present after treatment ceases.
      Gentamicin is the usual all-purpose agent of choice, tobramycin is slightly more
      effective against Pseudomonas aeruginosa infections, amikacin is the least
      susceptible to degradation by bacterial enzymes and netilmicin is probably the
      least toxic. Clinical and drug concentration monitoring have a role in therapy.
      Aminoglycosides exhibit enduring antibacterial activity (especially against Gram
      negative bacilli) many hours after tissue concentrations become negligible.
      Appreciation of this postantibiotic effect is leading to replacement of
      conventional multiple daily doses by large single daily doses. The latter
      regimens confer at least equivalent efficacy and less risk of toxicity
      (particularly renal). However, single daily dosage may be unsuitable for
      immunocompromised patients and in those with infective endocarditis, where there
      is insufficient experience. Cotreatment with beta-lactams is commonly used in
      order to exploit the synergism between these agents, particularly in enterococcal
      endocarditis and severe Gram-negative sepsis. Liposomal aminoglycosides are
      promising parenteral formulations. After being taken up by phagocytes they reach
      the liver, spleen and sites of inflammation; subsequently they are gradually
      released. To substantiate the applicability of these hitherto experimental
      formulations, findings from clinical studies are keenly awaited.

PMID- 7521832
TI  - Febrile seizures. Recognition and management.
AB  - The majority of all febrile seizures represent a benign syndrome that does not
      require extensive testing or long term medication. A careful history of the
      febrile seizure, family history, developmental history and physical examination
      can identify those infants and children with this syndrome. While one-third of
      this group will experience additional febrile seizures, there is no significant
      increase in the incidence of later epilepsy or neurological sequelae. The parents
      of these children need to be reassured and educated about this syndrome. They
      should understand the emergency treatment of seizures and aggressively treat
      fever. The more difficult task for the physician is to correctly identify those
      children who experience nonbenign seizures. Careful history and physical
      examination can accurately identify this group. Further evaluation including
      neuroimaging, electroencephalogram and developmental assessment may be necessary.
      In those children with a high risk of later epilepsy, treatment with an
      antiepileptic drug should be considered.

PMID- 7521836
TI  - Chicken antibodies to rabbit muscle actin with a restricted repertoire of F-actin
      recognition.
AB  - This report describes a polyclonal antibody against actin with unexpected and
      unusual properties. The antibody was raised in chicken immunized with a complex
      of DNase I and rabbit skeletal muscle actin, and purified from egg yolk by
      affinity chromatography. In Western blots, it reacted with alpha, beta and gamma
      isoforms of actin. In immunofluorescence and dot blot assays, however, it
      recognized selectively actin filaments in myofibrils, microvilli of brush border
      type epithelium and the "comet tails" of the intracellular parasite Listeria
      monocytogenes, while it did not react with stress fibers and peripheral belts of
      fibroblasts and epithelial cells, respectively. This reactivity pattern is
      reminiscent of that previously described for a monoclonal mouse antibody raised
      against smooth muscle actin (Sawtell et al., Cell Motil. Cytoskel. 11, 318,
      1988). The data presented in this study are consistent with the hypothesis that
      the chicken antibody recognizes an actin epitope/actin epitopes either accessible
      in only a subpopulation of microfilaments, or expressed only in a particular
      conformation of F-actin.

PMID- 7521837
TI  - Leptomeningeal infiltration in esthesioneuroblastoma: report of two cases with
      poor prognosis.
AB  - Esthesioneuroblastoma is a rare neoplasm of neuroectodermal origin, arising from
      the olfactory epithelium in the roof of the nasal cavity. Extension to the brain
      can occur less frequently than local recurrence, but leptomeningeal metastases
      without brain involvement have rarely been mentioned. We report 2 cases with poor
      prognosis of leptomeningeal infiltration during the evolution of
      esthesioneuroblastoma.

PMID- 7521835
TI  - Neocortical dendritic pathology in human partial epilepsy: a quantitative Golgi
      study.
AB  - We used a computerized image-analysis system to perform a quantitative analysis
      of rapid Golgi-impregnated pyramidal neurons of the third cortical layer of
      histologically normal cerebral cortex surgically removed from patients with
      partial epilepsy. Various parameters of 51 neurons from 9 patients and 29 neurons
      from 5 age-matched controls were compared. Dendritic spine density decreased
      progressively with increasing duration of seizures, and dendritic swellings were
      most numerous in epilepsy cases of uncertain etiology and in patients with
      seizures of longer standing. Neurons from seizure cases showed fewer dendritic
      branching points and fewer proximal dendritic branches than those from controls,
      suggesting a simplified dendritic architecture. These findings indicate that
      neurons in cortex distant from the primary site of epileptogenic activity may be
      undergoing subtle, progressive degeneration, which may explain the propensity of
      chronic epilepsy patients to have increased seizure activity and interictal
      behavioral and cognitive aberrations.

PMID- 7521838
TI  - Effect of arginine analogues on rat hind paw oedema and mast cell activation in
      vitro.
AB  - Nitro-L-arginine methyl ester (0.15 mumol/paw) significantly reduced both
      bradykinin- and 5-hydroxytryptamine-induced rat paw oedema. At this dose, L
      arginine (L-Arg), D-Arg and nitro-D-arginine methyl ester had no effect on the
      oedematogenic responses induced by these agents. Nitro-L-arginine methyl ester,
      nitro-D-arginine methyl ester, L-Arg, D-Arg, L-arginine methyl ester and L
      arginine ethyl ester, at the dose of 15 mumol/paw, significantly potentiated both
      bradykinin- and 5-hydroxytryptamine-induced oedema. This potentiation was not
      observed in animals treated with both mepyramine and methysergide or in animals
      chronically treated with compound 48/80. Nitro-L-arginine methyl ester (0.3-3 mM)
      and L-Arg (0.3-3 mM) released small amounts (< 10%) of histamine from rat
      peritoneal mast cells when compared to compound 48/80-induced degranulation (>
      40%). Histamine release was quantified by radioimmunoassay since nitro-L-arginine
      methyl ester and L-Arg interfere with the fluorometric assay. The potentiation of
      paw oedema observed with higher doses of all arginine analogues is caused by in
      vivo mast cell degranulation and is probably due to the cationic charge of these
      substances.

PMID- 7521831
TI  - Race and hypertension. What is clinically relevant?
AB  - Hypertension, once considered rare in Africa, occurs frequently in most Black
      populations outside of the continent as well as within more urban areas of
      Africa. The frequency of hypertension in Black citizens of the US is among the
      highest in the world. Pathophysiological mechanisms suggest the frequency of salt
      sensitive blood pressure is more common in Black patients. More Black than White
      patients initially present with volume expansion. However, in Black patients
      there appears to be no significant relationship between plasma renin activity,
      plasma volume and blood pressure. The syndrome of insulin resistance has also
      been reported in African Americans. Future studies should address this issue,
      both because it relates to identifying individuals at risk for development of
      high blood pressure and because it has implications for initial selection of
      antihypertensive therapy. Hypertensive kidney disease is prevalent in Black
      people. Lowering the blood pressure with diuretic-based therapies has not been
      shown to delay or prevent the loss of kidney function in patients with this
      condition, suggesting that this treatment approach may not be optimal. Lifestyle
      modifications remain the initial therapeutic regimen. Because diuretics and beta
      blockers have been shown to reduce cardiovascular morbidity and mortality in
      controlled clinical trials, they are preferred therapies. The Hypertension
      Detection and Follow-up Program showed significant reductions in morbidity and
      mortality in Black patients using primarily diuretic-based therapies. However,
      controversy persists regarding use of diuretics since some investigators believe
      that greater reductions in overall cardiovascular risk may be achieved in Black
      patients using other agents. These agents may eventually be able to exert a
      beneficial cardiovascular effect in addition to and independent of their blood
      pressure-lowering effect. Long term data documenting reduced morbidity and
      mortality rates with other agents are needed for all populations, particularly in
      Black hypertensive patients.

PMID- 7521834
TI  - Rifabutin. A review of its antimicrobial activity, pharmacokinetic properties and
      therapeutic efficacy.
AB  - Rifabutin is a derivative of rifamycin S with activity against mycobacteria
      including atypical organisms such as Mycobacterium avium and M. intracellulare,
      also referred to as Mycobacterium avium-intracellulare complex (MAC). To date,
      rifabutin is the only drug to have been studied in large prospective placebo
      controlled trials that has been shown to significantly reduce the incidence of
      disseminated MAC infection when administered prophylactically as a single agent
      to patients with acquired immune deficiency syndrome (AIDS). Initial studies also
      indicate that rifabutin may be a useful component of multiple drug regimens for
      the treatment of MAC infection, although further studies combining rifabutin with
      other recently available antimycobacterial drugs are required to determine the
      most effective regimens. When rifabutin is combined with at least two other
      antimycobacterial drugs, the combination appears to be of similar efficacy to
      rifampicin (rifampin)-containing regimens in patients with newly diagnosed
      pulmonary tuberculosis. Since available therapy for MAC infection in patients
      with AIDS is still suboptimal, rifabutin, at present the only first-line agent
      for prophylaxis against disseminated MAC infection in patients with advanced
      human immunodeficiency virus (HIV) infection, has the potential to make a
      valuable contribution to the continuing attempts to preserve the quality of life
      of patients with AIDS.

PMID- 7521839
TI  - Aggregation-induced association of syndecan-1 with microfilaments mediated by the
      cytoplasmic domain.
AB  - Expression of the transmembrane proteoglycan syndecan-1 in Schwann cells leads to
      enhanced spreading and cytoskeletal reorganization, but without an apparent
      stable association of syndecan-1 with cytoskeletal structures such as focal
      adhesions. Since cell surface oligomerization may be a mechanism for regulating
      the activities of transmembrane receptors, we wanted to investigate whether
      antibody-induced aggregation of the proteoglycan would promote its association
      with the cytoskeleton. When syndecan-1-expressing cells were incubated with anti
      syndecan-1 and anti-IgG antibodies, clustering of proteoglycan on the cell
      surface was observed by immunofluorescence microscopy. The resulting pattern of
      syndecan-1 distribution was very similar to that of the underlying microfilament
      network, as visualized by fluorescent-phalloidin staining. In cells that were
      fixed briefly with paraformaldehyde before addition of the anti-IgG antibodies no
      such colocalization of syndecan-1 and microfilaments was observed. Additional
      findings supported the conclusion that this pattern of syndecan-1 distribution
      reflected an association with microfilaments: aggregated syndecan-1 was resistant
      to extraction by nonionic detergent; incubation of the cells with cytochalasin b,
      but not colchicine, altered the pattern of aggregated syndecan-1 distribution;
      antibody-induced clustering of syndecan-1 led to a reorganization of actin
      filaments. Syndecan-1 remained on the cell surface following antibody-induced
      clustering, as revealed by immunogold staining and transmission electron
      microscopy. A mutant form of syndecan-1 lacking most of the cytoplasmic domain
      failed to exhibit actin filament association or induce actin reorganization
      following antibody-mediated aggregation. These results suggest that transient
      associations of syndecan family proteoglycans with microfilaments may be
      important aspects of their biological functions.

PMID- 7521840
TI  - A lipoxygenase metabolite, 12-(S)-HETE, stimulates protein kinase C-mediated
      release of cathepsin B from malignant cells.
AB  - The process of tumor cell invasion of the basement membrane is proposed to
      consist of three steps: attachment, local proteolysis and migration. 12-(S)-HETE,
      a 12-lipoxygenase metabolite of arachidonic acid, upregulates surface expression
      of integrin cytoadhesins and an autocrine motility factor receptor, suggesting
      that this metabolite may play an important regulatory function in tumor cell
      invasion. In the present study, we determined whether 12-(S)-HETE affects surface
      expression and/or release of cathepsin B, a cysteine protease that has been
      implicated in focal degradation of basement membrane. Secretion and distribution
      of cathepsin B was evaluated in two model systems for various stages of
      neoplastic progression: (i) murine B16 melanoma lines of low (B16-F1) and high
      (B16a) lung colonization potential, and (ii) immortalized and ras-transfected MCF
      10 human breast epithelial cells that differ in their invasive capacities in
      vitro. In the B16a cells, 12-(S)-HETE induced release of native and latent
      cathepsin B activity and concomitantly reduced cell-associated cathepsin B
      immunoreactivity. In contrast, 12-(S)-HETE did not induce the release of
      cathepsin B from B16-F1 cells, suggesting that there may be an enhanced response
      to 12-(S)-HETE in more malignant cells. This was confirmed in the MCF-10 system,
      in which 12-(S)-HETE was able to induce the release of cathepsin B from the ras
      transfected cells, but not from the immortal cells. A simultaneous reduction in
      staining for cathepsin B was observed in the ras-transfected cells, but not in
      their immortal counterparts. The release of cathepsin B may be mediated by PKC as
      pretreatment of B16a cells with the selective PKC inhibitor calphostin C, but not
      with the PKA inhibitor H8, prevented the stimulated release of cathepsin B. In
      B16a cells, the release of cathepsin B was accompanied by a translocation toward
      the cell periphery of vesicles staining for cathepsin B, resulting in focal areas
      of accumulation of cathepsin B. After 12-(S)-HETE stimulation of the ras
      transfected MCF-10 cells, cathepsin B was distributed homogeneously on the apical
      surface. Thus, 12-(S)-HETE can upregulate the surface expression on tumor cells
      of proteins able to mediate each of the three steps of tumor cell invasion:
      adhesion, degradation, and migration.

PMID- 7521841
TI  - Ultraviolet irradiation, although it activates the transcription factor AP-1 in
      F9 teratocarcinoma stem cells, does not induce the full complement of
      differentiation-associated genes.
AB  - Induction of differentiation of F9 teratocarcinoma stem cells by retinoic acid
      and cAMP has been shown to involve the activation of the transcription factor AP
      1 (a heterodimer of the proto-oncogene products c-Fos and c-Jun); moreover,
      stable expression of either Fos or Jun drives F9 cells into differentiation.
      Phorbol ester tumor promoters and short-wave-length ultraviolet (uv) irradiation
      are efficient inducers of AP-1 activity in various differentiated cells, but it
      has been shown that phorbol esters do not induce AP-1 activity in
      undifferentiated F9 cells. We examine here whether uv irradiation induces AP-1
      activity in these cells and drives F9 cells into differentiation. We show that uv
      induces, in contrast to phorbol esters, the formation of active AP-1 by
      activating transcription from the c-jun gene. Ultraviolet-induced AP-1 drives
      transcription from AP-1-dependent promoters coding for differentiation-associated
      proteins (such as urokinase and keratin 18). However, in uv-treated cells, these
      genes are activated earlier and to a greater extent than in cells treated with
      retinoic acid and cAMP. More importantly, uv, in contrast to retinoic acid and
      cAMP, does not induce the accumulation of collagen alpha 1 (IV) and laminin B1
      RNA. Our data suggest that the c-jun gene in F9 cells is accessible to immediate
      activation, but that uv-induced AP-1 activation does not suffice to induce the
      full program of F9 cell differentiation.

PMID- 7521842
TI  - Enhanced cell differentiation when RB is hypophosphorylated and down-regulated by
      radicicol, a SRC-kinase inhibitor.
AB  - Radicicol, an inhibitor of src or src-like kinases, causes hypophosphorylation
      and down-regulation of the RB retinoblastoma tumor suppressor protein in HL-60
      human promyelocytic leukemia cells. Both of these changes in the RB protein
      typically are associated with myeloid or monocytic differentiation of these cells
      induced by retinoic acid or 1,25-dihydroxy vitamin D3. When added with either
      inducer, radicicol caused the typically induced myeloid or monocytic
      differentiation of these cells to be accelerated. By itself radicicol caused a
      transient inhibition of G1 to S transit, but did not cause phenotypic conversion.
      The down-regulation and dephosphorylation of RB by radicicol may thus facilitate
      cell differentiation.

PMID- 7521843
TI  - Cell adhesion receptors for native and denatured type I collagens and fibronectin
      in rabbit arterial smooth muscle cells in culture.
AB  - Cell adhesion molecules serve as specific cell surface receptors for
      extracellular matrices and contribute to the attachment, spreading,
      proliferation, and differentiation of vascular cells. We examined the cell
      adhesion receptors and binding sites on native type I collagen, heat-denatured
      type I collagen, and fibronectin in rabbit arterial smooth muscle cells (SMC) in
      culture. On fibronectin, anti-alpha 3 beta 1 and anti-alpha 5 beta 1 integrin
      antibodies and the synthetic peptide GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro)
      significantly inhibited the attachment and spreading of rabbit SMC after 1 and 24
      h of culture, while anti-alpha 1 beta 1 inhibited attachment and spreading only
      after 1 h. In contrast, the attachment and spreading of the cells on native type
      I collagen were mediated by alpha 1 beta 1 integrin and the cell-binding sequence
      which did not contain RGD (Arg-Gly-Asp) and DGEA (Asp-Gly-Glu-Ala) after both 1
      and 24 h. On heat-denatured type I collagen, alpha 2 beta 1 integrin mediated the
      cell attachment and spreading after 1 and 24 h and DGEA served as a recognition
      site for the alpha 2 beta 1 integrin. alpha 1 beta 1 and alpha 3 beta 1 integrins
      affected only the initial adherence (1 h after plating) of the cells to denatured
      type I collagen. These findings suggest that rabbit SMC in culture can recognize
      the native and unfolded triple helical structures of type I collagen by
      interacting with the collagen fibril-binding receptor (alpha 1 beta 1 integrin)
      and collagen peptide-binding receptors (alpha 2 beta 1 and alpha 3 beta 1
      integrins). Moreover, alpha 1 beta 1 integrin may mediate the initial adherence
      to each substrate.

PMID- 7521844
TI  - Formation of focal adhesions by osteoblasts adhering to different substrata.
AB  - In this study, the adhesion of an osteoblast cell line to glass and titanium
      surfaces coated with different extracellular matrix components has been examined.
      On uncoated glass or titanium surfaces, osteoblasts attached but failed to
      spread. On these surfaces the cells did not develop focal adhesions or stress
      fibers. Precoating glass coverslips or titanium disks with fibronectin enhanced
      spreading and resulted in the rapid formation of focal adhesions and their
      associated stress fibers. Osteoblasts also spread and developed focal adhesions
      and stress fibers on glass or titanium coated with serum. In this situation the
      spreading was less rapid than that on fibronectin. Following incubation with
      serum, we demonstrated that the surfaces became coated with vitronectin. On the
      vitronectin-coated surfaces, it was shown that the osteoblast focal adhesions
      contained integrins of the beta 3 family. In contrast, osteoblasts adhering to
      fibronectin-coated surfaces accumulated beta 1 integrins within their focal
      adhesions. The enhanced formation of focal adhesions by osteoblasts plated on
      surfaces coated with extracellular matrix proteins suggests that precoating
      titanium and other implant materials with extracellular matrix proteins may
      improve osseointegration.

PMID- 7521845
TI  - Vitronectin in colorectal adenocarcinoma--synthesis by stromal cells in culture.
AB  - We have investigated the expression and cellular source of vitronectin in
      colorectal adenocarcinoma. Immunofluorescence staining of tissue sections
      revealed the presence of vitronectin in the stroma of the 11 tumors studied, but
      not in adjacent normal colon. A method was devised for the isolation from
      colorectal adenocarcinomas of fibroblast-like cells that stained positive for
      vimentin but negative for cytokeratin. These tumor-derived stromal cells
      synthesized and secreted vitronectin, as revealed by metabolic labeling and
      immunoprecipitation. This was confirmed by Southern blot analysis of polymerase
      chain reaction amplification products from reverse-transcribed RNA. Normal skin
      fibroblasts did not synthesize vitronectin. Immunofluorescence staining showed
      vitronectin deposited at focal contact sites in the tumor-derived cells, where it
      colocalized with vinculin and the alpha v integrin subunit. The deposition of
      vitronectin into focal contact sites was not dependent on the presence of serum.
      The finding that vitronectin can be synthesized and secreted by tumor-derived
      fibroblast-like cells in culture indicates that vitronectin expression can be
      promoted by as yet unknown signals provided in disease states, such as cancer.

PMID- 7521846
TI  - Estradiol-regulated transamidation of keratins by vaginal epithelial cell
      transglutaminase.
AB  - We have observed a marked increase in the activity of transglutaminase (EC
      2.3.2.13) in rat vaginal epithelial cells in a time-dependent manner during
      estradiol-induced terminal differentiation. The increased transglutaminase
      activity facilitates a post-translational modification, transamidation of
      keratins by the formation of an isopeptide sigma (tau-glutamyl) lysine. This
      isopeptide was recovered from the urea-soluble and -insoluble fractions of
      keratins. The formation of sigma (tau-glutamyl) lysine was significantly reduced
      in rats primed with progesterone or tamoxifen-estradiol. These in vivo
      experiments were further confirmed by in vitro studies using the reconstituted
      keratin filaments, which demonstrated a remarkable acceleration in the formation
      of covalent cross-links mediated by vaginal epithelial cell transglutaminase
      obtained from rats primed with estradiol. By specifically modifying the lysine
      residues of the keratins with 2,4-pentanedione the aggregation of keratin
      filaments was inhibited. These findings reflect that the vaginal epithelial cell
      transglutaminase obtained from rats which is regulated by estradiol plays a key
      role in the process of terminal differentiation of rat vaginal epithelial cells.

PMID- 7521833
TI  - Clodronate. A review of its pharmacological properties and therapeutic efficacy
      in resorptive bone disease.
AB  - Clodronate (clodronic acid, dichloromethylene bisphosphonate) is a bisphosphonate
      which has demonstrated efficacy in patients with a variety of diseases of
      enhanced bone resorption including Paget's disease, hypercalcaemia of malignancy
      and osteolytic bone metastases. In addition, early reports demonstrating
      potential efficacy of clodronate in the treatment of osteoporosis suggest a
      possible role in this debilitating disease. Short term intravenous administration
      (usually 300 mg/day for 5 days) or longer courses of oral clodronate (usually
      1600 mg/day for 6 months) effectively reduced bone pain and/or improved mobility
      in most patients with Paget's disease, and these effects persisted for up to 12
      months after discontinuing clodronate. When administered intravenously (300
      mg/day for up to 12 days) to patients with malignant hypercalcaemia, serum
      calcium levels declined significantly within 2 days of starting treatment and
      approximately 70 to 95% of patients became normocalcaemic. While there is less
      experience with oral administration, clodronate (800 to 3200 mg/day) achieved
      normocalcaemia in the majority of patients, usually within 1 week, and serum
      calcium levels remained significantly reduced from baseline for up to 6 months
      with continued treatment. Clodronate is clearly superior to placebo and, based on
      a retrospective analysis, appears to produce greater and more sustained
      reductions in serum calcium levels than calcitonin in patients with malignant
      hypercalcaemia. The few available prospective comparative trials showed that
      clodronate is at least as effective as etidronate, but comparisons with
      alendronate and pamidronate produced results of questionable clinical relevance
      because of low bisphosphonate dosages used in these trials. Nevertheless, single
      intravenous doses of clodronate 600 mg or alendronate 7.5 mg (both agents
      repeated on day 3 if necessary) were comparable in efficacy, whereas a single
      intravenous dose of pamidronate 30 mg was more effective than a single
      intravenous dose of clodronate 600 mg. Normocalcaemic patients with osteolytic
      bone metastases due to advanced breast cancer experienced significant reductions
      in the number of episodes of hypercalcaemia and terminal hypercalcaemia,
      incidence of vertebral fractures and overall rate of morbid events, including the
      need for radiotherapy to treat bone-related pain, following treatment with
      clodronate 1600 mg/day for 3 years in a large placebo-controlled study. A similar
      large placebo-controlled trial in patients with multiple myeloma demonstrated
      that clodronate 2400 mg/day orally for 2 years significantly reduced progression
      of osteolytic bone lesions. Follow-up data from clinical trials revealed that the
      effects on development of fractures and hypercalcaemia persisted for at least 12
      months after the drug was discontinued.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7521848
TI  - Cytokine-induced expression of nitric oxide synthase results in nitrosylation of
      heme and nonheme iron proteins in vascular smooth muscle cells.
AB  - Nitric oxide synthase (NOS) catalyzes the synthesis of the biomediator, nitric
      oxide (NO), from L-arginine. We have analyzed NOS induction and activity in
      cultured rat vascular smooth muscle cells (SMC), which respond to NO by
      relaxation and inhibition of mitochondrial respiration. Both interferon-gamma and
      tumor necrosis factor-alpha induced the expression of NOS mRNA and a combination
      of the two cytokines had a synergistic effect. An internal oligonucleotide
      complementary to murine macrophage NOS mRNA hybridized to polymerase chain
      reaction (PCR) products derived from SMC NOS but not brain NOS. Direct sequencing
      of the PCR products showed a high degree of homology between inducible NOS from
      SMC and macrophages. Analysis of NOS-dependent nitrite production demonstrated
      that the enzyme requires NADPH as a cofactor but not calcium for its activity.
      Cytokine treatment resulted in the development of electron paramagnetic resonance
      (EPR) signals characteristic for nitrosyl complexes, indicating nitrosylation of
      SMC molecules by enzymatically synthesized NO. De novo NOS gene transcription and
      protein synthesis are required for the cytokine-induced protein nitrosylation
      since addition of actinomycin D and cycloheximide abolished the cytokine effect.
      At an early stage of cytokine treatment and when low doses of cytokines were
      used, the EPR signal was dominated by a triplet hyperfine structure typical for
      hemenitrosyl complexes. With increasing incubation time and/or cytokine dose, the
      EPR spectra were gradually converted into a pattern resembling that of nonheme
      iron(II)-nitrosyl thiol complexes. Thereafter, the EPR signal shape no longer
      changed while the signal intensity increased quantitatively with NO synthesis,
      suggesting that considerable amounts of NO synthesized could be trapped in the
      cells by formation of nitrosyl complexes with intracellular molecules. Together,
      these results provide direct biochemical evidence for cytokine induction of NO
      synthesis and protein nitrosylation in SMC. This may represent an important
      second messenger system for cytokine effects on cellular metabolism in blood
      vessels.

PMID- 7521850
TI  - Fluorescent differential display: arbitrarily primed RT-PCR fingerprinting on an
      automated DNA sequencer.
AB  - We established robust, reliable protocols for 'Differential Display (DD),' an RNA
      fingerprinting method originally developed by Liang and Pardee [(1992) Science
      257, 967-971] using RT-PCR with arbitrary primers. Our protocols are optimized so
      that reliable DD analysis can be performed on a fluorescent DNA sequencer to
      ensure high throughput as well as improved operational safety, compared with the
      original one using radioactive compounds. Such 'Fluorescent Differential Display
      (FDD)' techniques will accelerate the identification of differentially expressed
      as well as polymorphic transcripts to address various biological questions.

PMID- 7521847
TI  - Mg2+ and Ca2+ differentially regulate beta 1 integrin-mediated adhesion of dermal
      fibroblasts and keratinocytes to various extracellular matrix proteins.
AB  - The specific requirements for divalent cations in the integrin-dependent adhesion
      and deadhesion of human dermal fibroblasts and human epidermal keratinocytes to
      various extracellular matrix proteins have been studied in vitro. The adhesion of
      both cell types to collagen type I and to laminin was enhanced by Mg2+ in a
      concentration-dependent manner, while Ca2+ dose-dependently antagonized this
      effect, thus promoting deadhesion. The cation-dependent conversion between
      adhesion and deadhesion occurred already at 2 to 10 min after addition of the
      alternate cation and was almost completed at 20 min. Interestingly, Ca2+ could
      not reverse the Mg(2+)-enhanced adhesion of both cell types to fibronectin.
      Inhibition studies with function-blocking antibodies directed against distinct
      beta 1 integrins showed that the Mg(2+)-enhanced fibroblast adhesion to collagen
      type I was mediated by the alpha 1 beta 1 and the alpha 2 beta 1 integrins,
      whereas keratinocyte adhesion to collagen type I was mediated by the alpha 2 beta
      1 integrin. Both cell types utilized the alpha 2 beta 1 and the alpha 6 beta 1
      integrins for Mg(2+)-dependent adhesion to laminin and the alpha 5 beta 1
      integrin for the adhesion to fibronectin. Integrin expression at the cell surface
      was not altered, indicating that divalent cation-dependent conformational changes
      of beta 1 integrins most likely regulate their functional activity.

PMID- 7521849
TI  - Bromelain protease F9 reduces the CD44 mediated adhesion of human peripheral
      blood lymphocytes to human umbilical vein endothelial cells.
AB  - The thiol protease bromelain has been shown to remove T-cell CD44 molecules from
      lymphocytes and to affect T-cell activation. We investigated the effect of a
      highly purified bromelain protease F9 (F9) on the adhesion of peripheral blood
      lymphocytes (PBL) to human umbilical vein endothelial cells (HUVEC).
      Preincubation of the lymphocytes with F9 reduced the adherence to about 20% of
      unstimulated and to about 30% of phorbol-dibutyrate (P(Bu)2) stimulated
      lymphocytes. Using flow cytometry, both crude bromelain and protease F9 reduced
      the expression of CD44, but not of LFA-1, on PBL. F9 was about 10 times more
      active than crude bromelain; at 2.5 micrograms/ml of F9 about 97% inhibition of
      CD44 expression was found. A mAb against CD44 was tested and found to block the
      F9-induced decrease in PBL-binding to HUVEC. The results indicate that F9
      selectively decreases the CD44 mediated binding of PBL to HUVEC.

PMID- 7521851
TI  - No requirement of reactive oxygen intermediates in Fas-mediated apoptosis.
AB  - Fas is a cell surface molecule that mediates apoptosis, but the intracellular
      mechanisms leading to apoptosis are not well understood. It is known that
      diethylmaleate (DEM)-induced cell death can be blocked by substances with
      antioxidant activity. Here we have studied whether antioxidants have any effect
      on Fas-mediated apoptosis and show that they are not able to block Fas-mediated
      apoptosis. Therefore, it seems that reactive oxygen intermediate (ROI)-dependent
      and -independent mechanisms which lead to apoptosis do exist. Fas-mediated
      apoptosis probably proceeds via a ROI-independent pathway.

PMID- 7521852
TI  - Activation of the alternative pathway of complement by apoptotic Jurkat cells.
AB  - Jurkat T cells die of apoptosis upon exposure to anti-Fas mAb. Here we show that
      although the alternative complement pathway generally does not attack homologous
      cells, anti-Fas-induced apoptotic Jurkat T cells were attacked antibody
      independently by the alternative pathway of human complement and opsonized with
      iC3b, which is a ligand of the complement receptor type 3 (CR3) of phagocytes.
      These results suggest that apoptotic cells become the targets of the homologous
      alternative complement pathway, which facilitates the clearance of apoptotic
      cells by phagocytes.

PMID- 7521853
TI  - Immunoregulation in fish. I: Intramolecular-induced suppression of antibody
      responses to haptenated protein antigens studied in Atlantic salmon (Salmo salar
      L).
AB  - We report here evidence for intramolecular-induced suppression of the in vivo
      antibody response in fish, using a panel of T-dependent hapten-carrier antigens.
      Atlantic salmon were immunized intraperitoneally with protein antigens (Limulus
      polyphemus hemocyanin, chicken gamma globulin, and Aeromonas salmonicida A-layer
      protein) given in their native form or haptenated with either 4-hydroxy-3-iodo-5
      nitrophenyl-acetic acid (NIP), 2,4,6-trinitrophenyl-acetic acid (TNP), or
      fluorescein-5-iso-thiocyanate (FITC). The salmon immune system responds to these
      hapten-carrier antigens by eliciting high anti-hapten titers whereas the antibody
      titers against protein determinants were suppressed 87-99%, determined by ELISA.
      NIP also induced suppression of the anti-FITC response when NIP and FITC were
      intramolecularly conjugated to Limulus polyphemus hemocyanin (LPH). The
      suppression was found to be independent of haptenation ratios and time after
      immunization. The possibility that haptenation interferes with or blocks the
      protein determinants is not likely because antisera raised against native LPH
      recognize LPH-specific epitopes even on heavily NIP-substituted LPH. Although the
      mechanism behind intramolecular-induced suppression is poorly understood, even in
      mammals, this study demonstrates that intramolecular-induced suppression may be
      one means by which antibody responses in fish are regulated. The possible impact
      of antigen-induced suppression on immune responses against vaccine antigens in
      fish is discussed.

PMID- 7521854
TI  - Functional heterogeneity of murine intestinal intraepithelial lymphocytes:
      studies using TCR-alpha beta+ IEL lines and fresh IEL isolates reveal multiple
      cytotoxic subsets differentiated by CD5, CD8 alpha/alpha, and CD8 alpha/beta
      expression.
AB  - Three T-cell lines, isolated from murine small intestine epithelia, have been
      studied with respect to phenotypic properties and cytotoxic activity. All lines
      were TCR-alpha beta+, Thy-1+, CD3+, CD4-, CD8+ but differed in that one line was
      CD8 alpha/alpha+, CD5-; one line was CD8 alpha/alpha+, CD5+; and one line was CD8
      alpha/beta+, CD5+. Both the CD8 alpha/alpha+, CD5-, and the CD8 alpha/beta+, CD5+
      lines lysed antigen-bearing target cells; however, the latter line also
      spontaneously lysed natural killer (NK)-sensitive target cells. The CD8
      alpha/alpha+, CD5+ IEL line was nonlytic for antigen-bearing target cells, for NK
      sensitive target cells, and in assays that detect lytic activity regardless of
      specificity. Three-color flow cytometric analyses of intestinal intraepithelial
      lymphocytes (IEL) in freshly-extracted preparations indicated that cells with the
      phenotypes of the three IEL lines are normally present in the murine intestine
      epithelium, and revealed considerable variability in the distribution and density
      of CD5 expression on murine IEL. In freshly extracted IEL depleted of CD5 or CD8
      beta by cell sorting, cytotoxicity was found to reside both within the CD5+ and
      the CD5- IEL subsets, as well as in the CD8 beta-depleted (i.e., CD8
      alpha/alpha+) subset. These findings demonstrate: that cytotoxicity of murine IEL
      resides among multiple phenotypic subsets; that the distribution and density of
      CD5 on IEL is more complex than previously described; and that T-cell lines of
      IEL origin are valuable for dissecting functional properties of specific IEL
      subsets, particularly those that constitute a small proportion of the total IEL.

PMID- 7521855
TI  - Inactivation of bleomycin by an N-acetyltransferase in the bleomycin-producing
      strain Streptomyces verticillus.
AB  - Bleomycin-producing Streptomyces verticillus ATCC15003 possesses a bleomycin
      acetyltransferase which inactivates the drug in the presence of acetyl coenzyme
      A. The site of acylation in enzymically prepared acetylbleomycin A2 was
      determined by nuclear magnetic resonance analysis; the primary amino group of the
      beta-aminoalanine moiety of bleomycin was acetylated Acetylbleomycin A2 had no
      detectable antibacterial activity and did not induce in vitro DNA degradation.

PMID- 7521856
TI  - Lack of effect of transdermal estrogen on the growth hormone-insulin-like growth
      factor axis.

PMID- 7521857
TI  - Monocyte differentiation and accessory function: different effects on the
      proliferative responses of an autoreactive T cell clone as compared to
      alloreactive or antigen-specific T cell lines and primary mixed lymphocyte
      cultures.
AB  - An autoreactive T cell clone derived from a patient with reactive arthritis, two
      alloreactive T cell lines, two antigen-specific T cell lines and allogeneic
      resting T cells were analyzed for their responses to monocytes and macrophages
      derived from monocytes by in vitro differentiation. The autoreactive T cell clone
      strongly proliferated in response to fresh monocytes and to macrophages derived
      from a 7 day culture, but only poorly to monocytes cultured for 2 days. In
      contrast, alloreactive and antigen-specific T cell lines proliferated to all
      stimulatory cells equally well. Finally, primary mixed lymphocyte reactions could
      be stimulated by both fresh and 2-day cultured monocytes, but not by in vitro
      derived macrophages. The impaired response of the autoreactive T cell clone to 2
      day cultured monocytes could not be attributed to reduced expression of several
      well-defined surface molecules nor to induction of nonresponsiveness. Neither
      allogeneic monocytes nor cytokines (IL-1, IL-2, IL-4, IL-6) could correct the
      defective response of the autoreactive T cell clone. However, preculture of
      monocytes in the presence of interferon-gamma, IL-1, IL-4 or IL-6 retained their
      stimulatory capacity. Our interpretation of the selectively impaired response of
      the autoreactive T cell clone is that it most likely recognizes a differentiation
      dependent monocyte/macrophage-specific peptide.

PMID- 7521861
TI  - Polyclonal antibody characterization of Babesia caballi antigens.
AB  - In a previous study diagnostic B. caballi antigens with apparent molecular mass
      of 50 and 48 kDa were identified. Another antigen of 141 kDa was recognized by
      most but not all B. caballi sera tested. Here a further characterization of the
      three antigens is reported. Rabbits were vaccinated with gel-purified antigens
      and monospecific antibodies were obtained for the 141 and 48 kDa antigens.
      Antibodies raised against the 50 kDa antigen cross-reacted with the 48 kDa
      antigen, suggesting that these two antigens bear unique as well as common
      epitopes. After two-dimensional electrophoresis the 50 and 48 kDa antigens were
      present as horizontal bands over a pH range from approximately 5.0-7.0 with
      focused spots at a pH of 5.5 and 5.9, respectively. The 141 kDa antigen was not
      present after two-dimensional electrophoresis. None of the three antigens could
      be identified as a glycoprotein. Judging from the immunofluorescence antibody
      test staining pattern obtained with the rabbit sera the 141 kDa antigen is
      present on the surface of infected erythrocytes. The 50 and 48 kDa antigens are
      located in the parasite itself and probably not on the surface of infected
      erythrocytes. The punctate staining pattern observed with the 48 kDa antiserum
      suggests that this antigen might be located in or associated with the apical
      complex of the parasite.

PMID- 7521859
TI  - Prediction of an HLA-B44 binding motif by the alignment of known epitopes and
      molecular modeling of the antigen binding cleft.

PMID- 7521858
TI  - Neuritogenic Lewis rat T cells use Tcrb chains that include a new Tcrb-V8 family
      member.
AB  - The P2 protein obtained from Schwann cells induces a population of T cells which,
      upon adoptive transfer, causes the disease experimental allergic neuritis (EAN),
      an animal model for Guillain-Barre syndrome. In this report, a truncated peptide,
      FR22, derived from a previously reported neuritogenic T-cell determinant, was
      used to generate from Lewis rats T cells that were shown to cause EAN. Since our
      previous studies showed that Tcrb-V8 was used by a majority of T-cell hybridomas
      specific for the neuritogenic peptide P26, which contains the FR22 sequence, we
      sequenced the Tcrb-V8+ mRNA from FR22-specific T-cell lines, and compared the
      sequences obtained with those obtained from similarly generated myelin basic
      protein (MBP) 68-88-specific Lewis rat T-cell lines. We found that in the EAN
      lines, several members of the Tcrb-V8 family were used, including a new family
      member, Tcrb-V8E. This was more diverse than the MBP-68-88-specific response in
      which only a single Tcrb-V8 family member was used. Also, in the EAN lines, the
      beta chain sequences did not show the same conserved junctional regions seen in
      the MBP lines. Thus, T-cell receptor beta chain usage in the response to this
      dominant neuritogenic peptide appears to be less restricted than the response to
      the dominant encephalitogenic determinant of MBP both in V region usage and in
      CDR3 usage.

PMID- 7521860
TI  - Peptide motifs of HLA-A3, -A24, and -B7 molecules as determined by pool
      sequencing.

PMID- 7521862
TI  - Differentiation of the various stages of Blastocystis hominis by acridine orange
      staining.
AB  - Acridine orange staining differentiates the cystic and the central body forms of
      Blastocystis hominis and offers a very convenient and easy method to observe the
      internal structure of the parasite. Acridine orange stains the nuclei and the
      central body of the rounded vacuolar forms of the parasite bright and dull green,
      respectively. The colour changes to yellow and then to flaming red-orange when
      the rounded central body forms of the parasite become cystic.

PMID- 7521863
TI  - Retreatment with radiotherapy for painful bone metastases.
AB  - PURPOSE: To evaluate the response to reirradiation of painful bone metastases
      following initial treatment with radiotherapy. METHODS AND MATERIALS: A
      retrospective analysis of 105 consecutive patients treated with palliative
      radiotherapy for painful bone metastases. A total of 280 individual treatment
      sites were identified, of which 57 were retreated once and 8 were retreated
      twice. RESULTS: The overall response rate to initial treatment was 84% for pain
      relief, and at first retreatment this was 87%. Seven of eight patients retreated
      a second time also achieved pain relief. No relation to radiation dose, primary
      tumor type, or site was seen. CONCLUSIONS: In patients relapsing after
      radiotherapy to painful bone metastases who have responded initially,
      reirradiation can be recommended with a similar probability of response.

PMID- 7521864
TI  - Analysis of the probability and risk of cause-specific failure.
AB  - PURPOSE: Kaplan-Meier curves are frequently misused in the analysis of
      nonsurvival endpoints, such as time to local failure or time to late
      complications. More appropriate analyses are available and described. METHODS AND
      MATERIALS: Cumulative incidence is an unbiased estimate of probability of cause
      specific failure. Cumulative conditional probability of cause-specific failure
      reflects risk to patients remaining at risk. Hazard rates also measure risk.
      RESULTS: Kaplan-Meier curves overestimate the probability of late complications
      when there is a high mortality rate. Cumulative incidence and cumulative
      conditional probability accurately give the probability and risk of cause
      specific failure. CONCLUSION: Kaplan-Meier analysis of cause-specific failure
      should be avoided because of its misinterpretation as an estimate of probability,
      in favor of appropriate methods.

PMID- 7521865
TI  - Palliative irradiation for bone metastasis--a new paradigm.

PMID- 7521866
TI  - Strategy for boron neutron capture therapy against tumor cells with over
      expression of the epidermal growth factor-receptor.
AB  - PURPOSE: Gliomas, squamous carcinomas and different adenocarcinomas from breast,
      colon and prostate might have an increased number of epidermal growth factor
      (EGF) receptors. The receptors are, in these cases, candidates for binding of
      receptor specific toxic conjugates that might inactivate cellular proliferation.
      The purpose of this study was to evaluate whether it is reasonable to try ligand
      dextran based conjugates for therapy. METHODS AND MATERIALS: EGF or TGF alpha
      were conjugated to dextran and binding, internalization, retention and
      degradation of eight types of such conjugates were analyzed in EGF-receptor
      amplified glioma cells. The conjugates were labelled with radioactive nuclides to
      allow detection and two of the conjugates were carrying boron in the form of
      carboranyl amino acids or aminoalkyl-carboranes. Comparative binding tests,
      applying 125I-EGF, were made with cultured breast, colon and prostate
      adenocarcinoma, glioma and squamous carcinoma cells. Some introductory tests to
      label with 76Br for positron emission tomography and with 131I for radionuclide
      therapy were also made. RESULTS: The dextran part of the conjugates did not
      prevent receptor specific binding. The amount of receptor specific binding varied
      between the different types of conjugates and between the tested cell types. The
      dextran part improved intracellular retention and radioactive nuclides were
      retained for at least 20-24 h. The therapeutical effect improved when 131I was
      attached to EGF-dextran instead of native EGF. CONCLUSION: The improved cellular
      retention of the ligand-dextran conjugates is an important property since it
      gives extended exposure time when radionuclides are applied and flexibility in
      the choice of time for application of neutrons in boron neutron capture therapy
      (BNCT). It is possible that ligand-dextran mediated BNCT might allow, if the
      applied neutron fields covers rather wide areas around the primary tumor, locally
      spread cells that otherwise would escape treatment to be inactivated.

PMID- 7521868
TI  - Adoption and psychiatric referral.

PMID- 7521867
TI  - Childhood-onset schizophrenia: timely neurobiological research.
AB  - OBJECTIVE: To review timely research on childhood-onset schizophrenia in view of
      advances in biological research on, and neurodevelopmental theories of, the later
      onset disorder. METHOD: Research issues are outlined including further
      clarification of ICD- and DSM-defined childhood schizophrenia, and
      differentiation from autism "spectrum" and other subtle, chronic developmental
      disorders. Key neurobiological advances are reviewed for which child studies are
      relevant and feasible. CONCLUSION: It is anticipated that narrowly defined
      childhood-onset schizophrenics will constitute a predominantly male population. A
      high rate of family illness or chromosomal and/or brain developmental
      abnormalities, which will be instructive regarding the pathophysiology of later
      onset schizophrenia, is expected.

PMID- 7521869
TI  - NADH dehydrogenase subunit genes in the mitochondrial DNA of yeasts.
AB  - The genes encoding the NADH dehydrogenase subunits of respiratory complex I have
      not been identified so far in the mitochondrial DNA (mtDNA) of yeasts. In the
      linear mtDNA of Candida parapsilosis, we found six new open reading frames whose
      sequences were unambiguously homologous to those of the genes known to code for
      NADH dehydrogenase subunit proteins of different organisms, i.e., ND1, ND2, ND3,
      ND4L, ND5, and ND6. The gene for ND4 also appears to be present, as judged from
      hybridization experiments with a Podospora gene probe. Specific transcripts from
      these open reading frames (ND genes) could be detected in the mitochondria.
      Hybridization experiments using C. parapsilosis genes as probes suggested that ND
      genes are present in the mtDNAs of a wide range of yeast species including
      Candida catenulata, Pichia guilliermondii, Clavispora lusitaniae, Debaryomyces
      hansenii, Hansenula polymorpha, and others.

PMID- 7521872
TI  - Sequencing analysis reveals a unique gene organization in the gyrB region of
      Mycoplasma hominis.
AB  - The homolog of the gyrB gene, which has been reported to be present in the
      vicinity of the initiation site of replication in bacteria, was mapped on the
      Mycoplasma hominis genome, and the region was subsequently sequenced. Five open
      reading frames were identified flanking the gyrB gene, one of which showed
      similarity to that which encodes the LicA protein of Haemophilus influenzae. The
      organization of the genes in the region showed no resemblance to that in the
      corresponding regions of other bacteria sequenced so far. The gyrA gene was
      mapped 35 kb downstream from the gyrB gene.

PMID- 7521870
TI  - Overexpression of algE in Escherichia coli: subcellular localization,
      purification, and ion channel properties.
AB  - Alginate-producing (mucoid) strains of Pseudomonas aeruginosa possess a 54-kDa
      outer membrane (OM) protein (AlgE) which is missing in nonmucoid bacteria. The
      coding region of the algE gene from mucoid P. aeruginosa CF3/M1 was subcloned in
      the expression vector pT7-7 and expressed in Escherichia coli. The level of
      expression of recombinant AlgE was seven times higher than that of the native
      protein in P. aeruginosa. Recombinant AlgE was found mainly in the OM. A putative
      precursor protein (56 kDa) of AlgE could be immunologically detected in the
      cytoplasmic membrane (CM). Surface exposition of AlgE in the OM of E. coli was
      indicated by labeling lysine residues with N-hydroxysuccinimide-biotin. Secondary
      structure analysis suggested that AlgE is anchored in the OM by 18 membrane
      spanning beta-strands, probably forming a beta-barrel. Recombinant AlgE was
      purified, and isoelectric focusing revealed a pI of 4.4. Recombinant AlgE was
      spontaneously incorporated into planar lipid bilayers, forming ion channels with
      a single-channel conductance of 0.76 nS in 1 M KCl and a mean lifetime of 0.7 ms.
      Single-channel current measurements in the presence of other salts as well as
      reversal potential measurements in salt gradients revealed that the AlgE channel
      was strongly anion selective. For chloride ions, a weak binding constant (Km =
      0.75 M) was calculated, suggesting that AlgE might constitute an ion channel
      specific for another particular anion, e.g., polymannuronic acid, which is a
      precursor of alginate. Consistent with this idea, the open-state probability of
      the channel decreased when GDP-mannuronic acid was added. The AlgE channel was
      inactivated when membrane voltages higher than +85 mV were applied. The
      electrophysiological characteristics of AlgE, including its rectifying
      properties, are quite different from those of typical porins.

PMID- 7521873
TI  - Contribution of gene conversion to the retention of the sequence for M blood
      group type determinant in glycophorin E gene.
AB  - M and N blood group antigens are presented by glycophorins A (GPA) and B (GPB) of
      the erythrocyte membrane. GPA expresses M or N blood group antigen depending on
      the allelic gene (GPAM gene or GPAN gene), while GPB expresses only the N
      antigen. M or N blood group antigen is specified by the first and fifth NH2
      terminal amino acid residues in the mature proteins, encoded by the second exon
      of these genes. Glycophorin E (GPE) gene, another member of this gene family, has
      a genomic structure very similar to that of GPB. However, a predicted product of
      GPE gene carries M blood group antigen. To delineate evolutionary events leading
      to the formation of the sequences for M or N blood group type determinant in the
      members of human glycophorin gene family, the nucleotide sequences of a 1.45
      kilobase pair region including the 3' part of intron 1, exon 2, and the entire
      intron 2 were compared for GPAM, GPAN, GPB, and GPE genes. Encompassing exon 2,
      there were identical sequences stretches of 139 and 138 base pairs between GPAM
      and GPE genes and between GPAN and GPB genes, respectively. The data of the
      entire sequences in this region revealed that the divergence of the sequence
      between GPE and GPA genes (2.14-2.49%) is less than that of the sequence between
      GPE and GPB genes (3.10%). The higher rate of divergence in this region was
      observed between GPA and GPB genes (3.79-3.86%). These results strongly suggest
      that GPE gene acquired the sequence for M blood group type determinant from GPAM
      gene through gene conversion after duplication of a progenitor gene common to GPB
      and GPE genes.

PMID- 7521871
TI  - Molecular analysis and characterization of a broad-host-range plasmid, pEP2.
AB  - Plasmid pEP2 was found to encode a protein, RepA, which is essential and rate
      limiting for its replication in Escherichia coli and Corynebacterium
      pseudotuberculosis. Mutations which altered the rate of synthesis of this protein
      in E. coli affected the copy number and segregational stability of pEP2 in the
      two hosts. RepA contains 483 amino acid residues and has the calculated molecular
      weight of 53,925. It shows 45% amino acid residue identity with open reading
      frame ORF2 of pSR1, a plasmid isolated from Corynebacterium glutamicum (J. A. C.
      Archer and A. J. Sinskey, J. Gen. Microbiol. 139:1753-1759, 1993). Plasmid pEP2
      was shown to accumulate single-stranded DNA corresponding to the RepA coding
      strand during its replication in E. coli and C. pseudotuberculosis, suggesting
      that it may replicate by a rolling circle mechanism. However, RepA has no
      significant sequence homology with the replication initiator proteins of plasmids
      known to use this mode of replication.

PMID- 7521874
TI  - The histidine-binding protein undergoes conformational changes in the absence of
      ligand as analyzed with conformation-specific monoclonal antibodies.
AB  - The periplasmic histidine-binding protein, HisJ, and the lysine-, arginine-,
      ornithine-binding protein (LAO) are receptors for histidine transport via the
      histidine permease of Salmonella typhimurium. The receptors have similar
      structures, being composed of two lobes held together by two peptide segments,
      with the ligand-binding site located in a cleft between the lobes. The two lobes
      are far apart in the unliganded structure (open conformation) and are drawn close
      together in the liganded structure (closed conformation). The tight binding of
      the ligand via protein side chains as well as the peptide backbone from both
      lobes stabilizes the closed conformation (Oh, B.-H., Pandit, J., Kang, C.-H.,
      Nikaido, K., Gokcen, S., Ames, G. F.-L., and Kim, S.-H. (1993) J. Biol. Chem.
      268, 11348-11353; Oh, B.-H., Kang, C.-H., De Bondt, H., Kim, S.-H., Nikaido, K.,
      Joshi, A., and Ames, G. F.-L. (1994) J. Biol. Chem. 269, 4135-4143). In this
      study two conformation-specific monoclonal antibodies (mAbs) that trap the
      protein in the closed empty form have been characterized and used to provide
      evidence that HisJ can assume the closed empty form in the absence of ligand.
      Several pieces of evidence were provided to demonstrate that these mAbs are
      specific for HisJ in the closed form. Histidine improves the interaction of these
      mAbs with immobilized HisJ. The mAbs inhibit both the exchange and the
      dissociation of histidine from HisJ, indicating that they are able to trap the
      protein in the closed liganded form. The characterization of the epitopes of the
      conformation-specific mAbs shows that they include residues that are located in
      both lobes and that are far apart in the open form but close to each other in the
      closed form, so that the mAbs must be sensitive to their spatial orientation. Two
      mAbs that are not conformation-specific according to these criteria were also
      identified.

PMID- 7521875
TI  - Specific inhibition of viral protein synthesis in HIV-infected cells in response
      to interferon treatment.
AB  - The mechanism of action of different types of interferons (IFN-alpha, -beta, and 
      gamma) against human immunodeficiency virus (HIV)-1 infection was investigated in
      chronically infected monocytoid U937 cells and during an acute infection of the T
      lymphoblastoid CEM cells. Two chronically infected U937 cell populations,
      obtained independently (referred to as type A and B cells), were analyzed for
      their response to IFNs. In type A cells, IFNs mainly inhibited virus particle
      release, whereas in type B cells, the anti-HIV effect of IFNs cells was found to
      be largely due to a specific inhibition of viral protein synthesis without any
      apparent effect on total cellular protein synthesis. Interestingly, such a
      differential inhibition of HIV protein synthesis could also be demonstrated in
      acutely infected CEM cells in response to treatment with IFN-alpha. Both in
      chronically infected U937 type B and acutely infected CEM cells, equivalent
      amounts of nuclear and cytoplasmic HIV-1 mRNA were detected in control and IFN
      treated cells in spite of at least 80% inhibition of HIV protein synthesis.
      Analysis of the distribution of cellular and viral mRNAs on polysomes in HIV-1
      infected cells demonstrated that IFN treatment induces a specific block on viral
      mRNA translation. These results indicate that the antiviral mechanism of IFN on
      later stages of HIV replication cycle may be partly due to the inhibition of HIV
      mRNA translation, besides an effect on virus budding or release.

PMID- 7521876
TI  - Role of O-linked carbohydrate chains on leukocyte cell membranes in platelet
      induced leukocyte activation.
AB  - We previously reported that activated platelets stimulated neutrophils and
      monocytes to produce superoxide anion (O2-) through the interaction between P
      selectin and its carbohydrate ligand, sialyl Lewis X (sLeX) (Nagata, K., Tsuji,
      T., Todoroki, N., Katagiri, Y., Tanoue, K., Yamazaki, H., Hanai N., and Irimura,
      T. (1993) J. Immunol. 151, 3267-3273). In the present study, we investigated the
      role of cell surface carbohydrate chains of leukocytes in this process.
      Glycoconjugate-specific hydrolytic enzymes and inhibitors of glycosylation
      processing were applied. Granulocyte-like differentiated HL-60 (gHL-60) cells
      released an increased amount of O2- in response to activated platelets in a P
      selectin-dependent manner. When HL-60 cells were differentiated in the presence
      of benzyl-alpha-N-acetylgalactosaminide (Bzl-alpha-GalNAc), an inhibitor of chain
      elongation of O-linked carbohydrates, the enhanced generation of O2- was
      abrogated in parallel with decrease in the expression of sLex structure and in
      the adhesion capacity to activated platelets. In contrast, treatment with
      swainsonine or 1-deoxymannojirimycin, inhibitors of processing of N-linked
      carbohydrate chains, did not show such effects. O-Sialoglycoprotease treatment of
      gHL-60 cells decreased the activated platelet-induced O2- production with
      concomitant reduction of cell surface sLex expression. Treatment of these cells
      with N-glycanase did not affect the O2- production. These results strongly
      suggested that serine/threonine-linked carbohydrate chains containing sLex played
      an essential role in the P-selectin-mediated leukocyte activation. By Western
      blotting analysis of gHL-60 cell lysates, we identified two glycoproteins which
      carried sLex structures and were sensitive to Bzl-alpha-GalNAc treatment.

PMID- 7521877
TI  - Expression of receptor-like protein tyrosine phosphatase alpha in rat embryo
      fibroblasts activates mitogen-activated protein kinase and c-Jun.
AB  - Anti-c-Src and anti-phosphotyrosine immunoprecipitates from receptor-like protein
      tyrosine phosphatase alpha (PTP alpha)-transfected and control rat embryo
      fibroblasts contain a 39-kDa phosphoprotein (p39) whose phosphorylation is
      enhanced by PTP alpha expression. The p39 that co-immunoprecipitates with c-Src
      has been identified as c-Jun by immunological and functional criteria; it is
      recognized by several different anti-c-Jun antibodies and binds to a c-Jun
      recognition element-containing oligonucleotide. Whereas the association of c-Src
      and c-Jun is unexpected, it may be of significance in PTP alpha signaling since
      we have previously demonstrated that c-Src is activated by PTP alpha (Zheng, X.
      M., Wang, Y., and Pallen, C. J. (1992) Nature 359, 336-339. Examination of c-Jun
      activity in these fibroblasts demonstrates that c-Jun DNA binding activity and c
      Jun-mediated transcription of a chloramphenicol acetyltransferase reporter gene
      are elevated in PTP alpha-expressing cells. In addition to c-Jun activation,
      mitogen-activated protein kinase is activated in PTP alpha-expressing cells and
      translocated to the nuclei of these cells. The nuclear localization of activated
      mitogen-activated protein kinase and c-Jun suggests that their activation
      represents downstream events in the receptor-like PTP alpha-initiated signaling
      pathway(s).

PMID- 7521878
TI  - The P-selectin glycoprotein ligand from human neutrophils displays sialylated,
      fucosylated, O-linked poly-N-acetyllactosamine.
AB  - We previously demonstrated that P-selectin binds with high affinity to a trace,
      homodimeric glycoprotein ligand on human myeloid cells. The ligand carries the
      sialyl Lewis x (sLe(x)) epitope, a limited number of N-linked glycans, and
      clustered, sialylated O-linked glycans. In this study we demonstrate that the
      polypeptide component of this ligand is identical to that of P-selectin
      glycoprotein ligand-1 (PSGL-1), a molecule recently identified by expression
      cloning from a human myeloid cell cDNA library. We have examined the effects of
      glycosidases on purified, radioiodinated PSGL-1 from human neutrophils to further
      characterize the structure and function of the attached oligosaccharides. We
      found that PSGL-1 had poly-N-acetyllactosamine, only some of which could be
      removed with endo-beta-galactosidase. The majority of the Le(x) and sLe(x)
      structures were on endo-beta-galactosidase-sensitive chains. Peptide:N
      glycosidase F (PNGaseF) treatment removed at least two of the three possible N
      linked oligosaccharides from PSGL-1. Expression of Le(x) and sLe(x) was not
      detectably altered by PNGaseF digestion, indicating that these structures were
      primarily on O-linked poly-N-acetyllactosamine. Endo-beta-galactosidase-treated
      PSGL-1 retained the ability to bind to P-selectin, suggesting that some of the
      oligosaccharides recognized by P-selectin were either on enzyme-resistant poly-N
      acetyllactosamine or on chains which lack poly-N-acetyllactosamine. PNGaseF
      treatment did not affect the ability of PSGL-1 to bind to P-selectin,
      demonstrating that the oligosaccharides required for P-selectin recognition are O
      linked. PSGL-1 also bound to E-selectin, but with at least 50-fold lower affinity
      than to P-selectin. These data suggest that PSGL-1 from human neutrophils
      displays complex, sialylated, and fucosylated O-linked poly-N-acetyllactosamine
      that promote high affinity binding to P-selectin, but not to E-selectin.

PMID- 7521879
TI  - Covalent attachment of charybdotoxin to the beta-subunit of the high conductance
      Ca(2+)-activated K+ channel. Identification of the site of incorporation and
      implications for channel topology.
AB  - Purified high conductance Ca(2+)-activated K+ (maxi-K) channels from bovine
      tracheal smooth muscle have been covalently labeled employing monoiodotyrosine
      charybdotoxin ([125I]ChTX) and different bifunctional cross-linking reagents.
      [125I]ChTX was specifically incorporated into the beta-subunit, which was
      thereafter isolated by size exclusion high performance liquid chromatography.
      Proteolytic fragments of the [125I]ChTX-labeled beta-subunit were generated by
      digestion with various endoproteinases. Glu-C or Asp-N cleavage yielded a
      glycosylated [125I]ChTX-labeled fragment of 13-14 kDa. A site-directed antiserum
      raised against residues 62-75 of the cloned beta-subunit of the maxi-K channel
      specifically recognizes the beta-subunit in immunostaining experiments and was
      capable of immunoprecipitating these ChTX-labeled peptides. Lys-C cleavage
      resulted in two fragments of 16 and 28 kDa, respectively, which were both
      precipitated by anti-beta (62-75). However, only the 28-kDa fragment was
      recognized by anti-beta(118-132) and shown to carry double the amount of N-linked
      carbohydrates. Taken together, these data restrict the site of covalent
      incorporation of ChTX into the beta-subunit exclusively at Lys69, confirm the
      predicted topology of this subunit, and indicate that both canonical N-linked
      glycosylation sites are occupied with complex carbohydrates of 5-6 kDa each. We
      propose that an extracellularly located portion of the beta-subunit is located
      within 7.7 A of the ChTX receptor site and could even participate in the
      formation of this receptor by close apposition of its extracellular domain with
      structural elements provided by the alpha-subunit.

PMID- 7521880
TI  - Focal adhesion kinase is abundant in developing blood vessels and elevation of
      its phosphotyrosine content in vascular smooth muscle cells is a rapid response
      to angiotensin II.
AB  - Focal adhesion kinase (FAK) is a structurally unique nonreceptor protein-tyrosine
      kinase that localizes to focal adhesion plaques. Regulation of its activity has
      been implicated in diverse signaling pathways, including those mediated by
      extracellular matrix/integrin interactions, G-protein coupled receptors for
      mitogenic neuropeptides, and certain oncogene products. To gain evidence for
      specific processes in which FAK may be involved in vivo, a study was initiated to
      determine its expression pattern during mouse development. FAK expression was
      detected in early embryos and appeared to be distributed throughout all cell
      types at about the time of neurulation. Subsequent to neural tube closure,
      expression became particularly abundant in the developing vasculature. This
      included expression in the medial layer of arteries populated by smooth muscle
      cells. In vitro studies using cultured rat aortic vascular smooth muscle cells
      demonstrate that FAK phosphotyrosine content is dramatically elevated in response
      to plating cells onto the adhesive glycoprotein, fibronectin. Also, enhanced
      tyrosine phosphorylation of FAK is observed in these cells upon stimulation with
      the vasoconstrictor angiotensin II. Thus, in vascular smooth muscle cells, like
      fibroblasts, FAK appears to play a role in signaling mechanisms induced by
      extracellular matrix components as well as G-protein coupled receptor agonists.
      The combined results of this study suggest that signaling through FAK may play an
      important role in blood vessel morphogenesis and function.

PMID- 7521881
TI  - Prostate cancer screening: a place for informed consent?

PMID- 7521882
TI  - Human red cell aquaporin CHIP. I. Molecular characterization of ABH and Colton
      blood group antigens.
AB  - Blood group antigens are structural variants in surface carbohydrate or amino
      acid polymorphisms on extracellular domains of membrane proteins. The red cell
      water channel-forming integral protein (Aquaporin CHIP) is a homotetramer with
      only one N-glycosylated subunit, however no CHIP-associated blood group antigens
      have yet been identified. Immunoblotting, monosaccharide composition analysis,
      and selective glycosidase digestions revealed that the CHIP-associated
      oligosaccharide contains ABH determinants and resembles a band 3-type glycan that
      cannot be cleaved from intact membranes by Peptide:N-glycosidase F. The molecular
      structure of the Colton antigens was previously unknown, but CHIP was selectively
      immunoprecipitated with anti-Coa or anti-Co(b). The DNA sequence from Colton
      typed individuals predicted that residue 45 is alanine in the Co(a+b-) phenotype
      and valine in the Co(a-b+) phenotype. The nucleotide polymorphism corresponds to
      a PflMI endonuclease digestion site in the DNA from Co(a-b+) individuals. These
      studies have defined antigens within two blood group systems on CHIP: (a) an ABH
      bearing polylactosaminoglycan attached to a poorly accessible site in the native
      membrane; and (b) the Colton antigen polymorphism which may permit the
      identification of rare individuals with defective water channel expression.

PMID- 7521883
TI  - Human red cell Aquaporin CHIP. II. Expression during normal fetal development and
      in a novel form of congenital dyserythropoietic anemia.
AB  - Channel-forming integral protein (CHIP) is the archetypal member of the Aquaporin
      family of water channels. Delayed CHIP expression was shown recently in perinatal
      rat (Smith, B. L., R. Baumgarten, S. Nielsen, D. Raben, M. L. Zeidel, and P.
      Agre. 1993. J. Clin. Invest. 92:2035-2041); here we delineate the human patterns.
      Compared with adult, second and third trimester human fetal red cells had lower
      CHIP/spectrin ratios (0.72 +/- 0.12, 0.94 +/- 0.22 vs 1.18 +/- 0.11) and reduced
      osmotic water permeability (0.029, 0.026 vs 0.037 cm/s); CHIP was already present
      in human renal tubules by the second trimester. A patient with a novel form of
      congenital dyserythropoietic anemia (CDA) with persistent embryonic and fetal
      globins and absent red cell CD44 protein was studied because of reduced CHIP
      associated Colton antigens. Novel CDA red cells contained < 10% of the normal
      level of CHIP and had remarkably low osmotic water permeability (< 0.01 cm/s),
      but no mutation was identified in Aquaporin-1, the gene encoding CHIP. These
      studies demonstrate: (a) unlike rat, human CHIP expression occurs early in fetal
      development; (b) red cell water channels are greatly reduced in a rare phenotype;
      and (c) disrupted expression of red cell CHIP and CD44 suggests an approach to
      the molecular defect in a novel form of CDA.

PMID- 7521884
TI  - C5a-induced expression of P-selectin in endothelial cells.
AB  - Human umbilical vein endothelial cells have recently been shown to respond to C5a
      with increases in intracellular Ca2+, production of D-myo-inositol 1,4,5
      triphosphate and superoxide anion generation. In the current studies, C5a had
      been found to cause in a time- and dose-dependent manner rapid expression of
      endothelial P-selectin, secretion of von Willebrand factor, and adhesiveness for
      human neutrophils. The effects of C5a in P-selectin expression and adhesiveness
      of neutrophils were similar to the effects of histamine and thrombin on
      endothelial cells. The adhesiveness of C5a-stimulated endothelium for neutrophils
      was blocked by anti-P-selectin, but not by antibodies to intercellular adhesion
      molecule 1, E-selectin, or CD18. A cell-based ELISA technique has confirmed
      upregulation of P-selectin in endothelial cells exposed to C5a. Binding of C5a to
      endothelial cells has been demonstrated, with molecules bound being approximately
      10% of those binding to neutrophils. By a reverse transcriptase-PCR technique,
      endothelial cells have been shown to contain mRNA for the C5a receptor. These
      data suggest that C5a may be an important inflammatory mediator for the early
      adhesive interactions between neutrophils and endothelial cells in the acute
      inflammatory response.

PMID- 7521885
TI  - Cyclic guanosine monophosphate is the mediator of platelet-activating factor
      inhibition on transport by the mouse kidney thick ascending limb.
AB  - Since we have previously shown a direct inhibitory effect of platelet-activating
      factor (PAF) on Cl reabsorption in the medullary thick ascending limb of Henle's
      loop (TAL), the aim of this study was to extend this effect to the whole TAL and
      to further investigate the signaling pathway involved. In microperfused cortical
      TALs, PAF significantly decreased Cl reabsorption by 50.3 +/- 6.5%. On the one
      hand, this effect was not modified in the presence of staurosporine and was not
      mimicked by phorbol ester; chelating cytosolic Ca by BAPTA/AM failed to suppress
      the inhibitory effect of PAF on Cl reabsorption; moreover, no significant
      increase in intracellular Ca concentration could be observed in the presence of
      PAF on isolated tubules. On the other hand, 8-bromo cyclic GMP mimicked the PAF
      effect on Cl reabsorption and prevented a further effect of this agent; the PAF
      effect was significantly reduced by H-8, a cyclic GMP-dependent protein kinase
      inhibitor; in medullary TALs, PAF significantly increased by twofold cyclic GMP
      content, an effect inhibited by the PAF antagonist BN 50730, whereas PAF did not
      significantly modify cAMP content in basal or stimulated conditions. Finally,
      inhibition of nitric oxide production by NAME or NMMA failed to prevent the
      effect of PAF on Cl reabsorption. It is concluded that the PAF-induced inhibition
      of Cl reabsorption in the TAL was mediated by cyclic GMP, likely independent of a
      nitric oxide synthesis.

PMID- 7521886
TI  - Long-term impaired neutrophil migration in mice overexpressing human interleukin
      8.
AB  - The proinflammatory chemokine interleukin-8 (IL-8/NAP-1) has been implicated in
      recruiting neutrophils to sites of acute and chronic tissue inflammation. In
      transgenic mice, elevated serum IL-8 levels ranging from 1 to 118 ng/ml were
      correlated with proportional increases in circulating neutrophils and
      proportional decreases in L-selectin expression on the surface of blood
      neutrophils. No change in the expression of the beta 2-integrins Mac-1 and LFA-1
      was apparent on peripheral blood neutrophils of the IL-8 transgenic mice.
      Additionally, L-selectin expression on bone marrow neutrophils and neutrophil
      precursors was normal in all transgenic lines. IL-8 transgenic mice demonstrated
      an accumulation of neutrophils in the microcirculation of the lung, liver and
      spleen. Moreover, there was no evidence of neutrophil extravasation, plasma
      exudation or tissue damage in any IL-8 transgenic mice. Neutrophil migration into
      the inflamed peritoneal cavity was severely inhibited in IL-8 transgenic mice,
      but not in nontransgenic littermates. The IL-8 transgenic mice should serve as
      useful models for studying the putative role of neutrophils in mediating tissue
      damage in models of inflammation, such as hepatic ischemia and reperfusion
      injury, cecal puncture and ligation, and glomerulonephritis.

PMID- 7521887
TI  - Tissue factor controls the balance of angiogenic and antiangiogenic properties of
      tumor cells in mice.
AB  - Meth-A sarcoma cells were stable transfected to overexpress (sense construct) or
      underexpress (antisense construct) tissue factor. In vitro, there was no
      difference in plating efficiency or growth between these cell lines. In vivo,
      tumor cells transfected to overexpress tissue factor grew more rapidly, and
      established larger and more vascularized tumors than control transfectants.
      Antisense transfectants grew the slowest and were the least vascularized.
      Anticoagulation of mice with warfarin did not alter the difference between these
      tumor lines. Tumor cells over-expressing tissue factor released more (compared
      with control transfectants) mitogenic activity for endothelial cells in parallel
      with enhanced transcription of vascular permeability factor/vascular endothelial
      cell growth factor (VEGF/VPF), and diminished transcription of thrombospondin
      (TSP2), a molecule with anti-angiogenic properties. Antisense tissue factor
      transfectants, while releasing the lowest amount of mitogenic activity, had
      increased thrombospondin and decreased VEGF/VPF transcription compared with
      control transfectants or wild-type cells. Experiments with these sense,
      antisense, truncated sense, or vector tumor lines gave comparable results in
      complete medium, serum free medium or in the presence of hirudin, indicating that
      the activation of the coagulation mechanism was not likely to be responsible for
      changes in tumor cell properties. These results suggest that tissue factor
      regulates angiogenic properties of tumor cells by altering the production of
      growth regulatory molecules of endothelium by a mechanism distinct from tissue
      factor activation of the coagulation mechanism.

PMID- 7521888
TI  - Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and
      chronic forms of graft-vs-host disease.
AB  - Chronic and acute graft-versus-host disease (cGVHD and aGVHD) result from donor
      cells responding to host disparate MHC alleles. In cGVHD (H-2d-->H-2bd),
      heightened polyclonal immunoglobulin production is due to the interaction of
      donor allospecific helper T cells (Th) and the host B cells. In vivo
      administration of antibody to the ligand for CD40, gp39, blocked cGVHD-induced
      serum anti-DNA autoantibodies, IgE production, spontaneous immunoglobulin
      production in vitro, and associated splenomegaly. Antibody production remained
      inhibited for extended periods of time after termination of anti-gp39
      administration. Antiallogeneic CTL responses induced in a GVHD were also
      prevented by the in vivo administration of anti-gp39 as was the associated
      splenomegaly. These data suggest that CD40-gp39 interactions are critical in GVHD
      and that CD40-gp39 may be a valuable ligand-receptor pair for targeting
      immunotherapeutic agents to control GVHD.

PMID- 7521889
TI  - In healthy primates, circulating autoreactive T cells mediate autoimmune disease.
AB  - A T cell response against myelin basic protein (MBP) is thought to contribute to
      the central nervous system (CNS) inflammation that occurs in the human
      demyelinating disease multiple sclerosis. To test whether MBP-reactive T cells
      that are normally retrieved from the circulation are capable of inducing CNS
      disease, MBP-reactive T cell clones were isolated from the peripheral blood of
      healthy, unimmunized Callithrix jacchus (C. jacchus) marmosets. This primate
      species is characterized by a natural chimerism of bone marrow elements between
      siblings that should make possible adoptive transfer of MBP-reactive T cells. We
      report that MBP-reactive T cell clones efficiently and reproducibly transfer CNS
      inflammatory disease between members of C. jacchus chimeric sets. The
      demyelination that is characteristic of experimental allergic encephalomyelitis
      induced in C. jacchus by immunization against human white matter did not occur
      after adoptive transfer of the MBP-reactive clones. It was noteworthy that
      encephalitogenic T cell clones were diverse in terms of their recognition of
      different epitopes of MBP, distinguishing the response in C. jacchus from that in
      some inbred rodents in which restricted recognition of MBP occurs. These findings
      are the first direct evidence that natural populations of circulating T cells
      directed against a CNS antigen can mediate an inflammatory autoimmune disease.

PMID- 7521891
TI  - Modification of alternative messenger RNA splicing of fibroblast growth factor
      receptors in human cardiac allografts during rejection.
AB  - Accelerated coronary atherosclerosis in cardiac transplants (cardiac allograft
      vasculopathy, CAV) is characterized by coronary intimal hyperplasia. Acidic
      fibroblast growth factor (aFGF) is a potent mitogen for vascular smooth muscle
      cells and endothelial cells, and its expression is increased in cardiac
      allografts, suggesting it may play a role in the pathogenesis of CAV. The
      activity of aFGF is dependent on binding to transmembrane receptors. To
      investigate whether receptors for aFGF are also induced after transplantation,
      polymerase chain reaction, in situ hybridization, and immunohistochemistry were
      used to analyze expression of four receptors for aFGF (FGFR1-FGFR4). Expression
      of mRNA encoding extracellular immunoglobulin-like domains of FGFR1 was increased
      35-fold in cardiac allografts compared with normal hearts and was predominantly
      present in cardiac myocytes and vascular structures. Alternatively spliced mRNA
      that encodes transmembrane forms of FGFR1, which contain the signal-transducing
      tyrosine kinase domains, was induced in allografts during rejection, in
      infiltrating cells, vascular structures, and myocytes. In vitro experiments
      showed that differential expression of FGF receptor isoforms was induced by aFGF,
      and also by IL-6 and TGF-beta, which are expressed in cardiac allografts during
      rejection. The results show that expression of both aFGF and its receptors is
      altered in cardiac allografts and suggest that these events are important in the
      pathogenesis of CAV.

PMID- 7521890
TI  - Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells.
      Induction and modulation of sensitivity by cytokines.
AB  - Fas/APO-1 is a transmembrane protein of the nerve growth factor/TNF alpha
      receptor family which signals apoptotic cell death in susceptible target cells.
      We have investigated the susceptibility of seven human malignant glioma cell
      lines to Fas/APO-1-dependent apoptosis. Sensitivity to Fas/APO-1 antibody
      mediated cell killing correlated with cell surface expression of Fas/APO-1.
      Expression of Fas/APO-1 as well as Fas/APO-1-dependent cytotoxicity were
      augmented by preexposure of human malignant glioma cells to IFN gamma and TNF
      alpha. Further, pretreatment with TGF beta 2, IL1 and IL8 enhanced Fas/APO-1
      antibody-induced glioma cell apoptosis whereas other cytokines including TNF
      beta, IL6, macrophage colony-stimulating factor, IL10 and IL13 had no such
      effect. None of the human malignant glioma cell lines was susceptible to TNF
      alpha-induced cytotoxicity. Fas/APO-1 antibody-sensitive glioma cell lines (n =
      5), but not Fas/APO-1 antibody-resistant glioma cell lines (n = 2), became
      sensitive to TNF alpha when co-treated with inhibitors of RNA and protein
      synthesis. Resistance of human glioma cells to Fas/APO-1 antibody-mediated
      apoptosis was mainly related to low level expression of Fas/APO-1 and appeared
      not to be linked to overexpression of the anti-apoptotic protooncogene, bcl-2.
      Given the resistance of human malignant glioma to surgery, irradiation,
      chemotherapy and immunotherapy, we propose that Fas/APO-1 may be a promising
      target for a novel locoregionary approach to human malignant glioma. This
      strategy gains support from the demonstration of Fas/APO-1 expression in ex vivo
      human malignant glioma specimens and from the absence of Fas/APO-1 in normal
      human brain parenchyma.

PMID- 7521893
TI  - Evaluation of three antidotes on arsenic toxicity in the common earthworm
      (Lumbricus terrestris).
AB  - The common earthworm (Lumbricus terrestris) is being evaluated in our
      laboratories as a substitute for mice in metal toxicity studies. These two
      disparate species have enzymes in common, such as catalase, superoxide dismutase
      and glutathione-S-transferase. Also, worms respond similarly to these rodents for
      selenium and nickel toxicity. Worms are less sensitive, however, to metal
      toxicity. In this study earthworms were challenged with three different arsenic
      compounds: arsenite, arsenate and the vesicant phenyldichloroarsine (PDA). The
      median lethal dose for each arsenic compound was determined. The order of
      toxicity of the arsenic compounds to the worms was PDA > arsenite > arsenate (24
      h LD50 values were 189.5, 191.0 and 519.4 mumol kg-1, respectively). Individual
      mammalian dithiol antidotes, namely the sodium salt of 2,3-dimercapto-1
      propanesulfonic acid (DMPS), meso-dimercaptosuccinic acid (DMSA) or 2,3
      dimercapto-1-propanol (BAL), were injected into the worms 5 min after various
      doses of the arsenic compound were administered. The decreases in acute toxicity
      values were recorded. All three antidotes protected the worms against arsenic
      toxicity with varying degrees of effectiveness. The protective action for the
      inorganic arsenic compounds was in the order DMPS > DMSA > BAL. For the organic
      arsenical, PDA, the most effective antidote was BAL.

PMID- 7521892
TI  - Monoclonal antibodies to group II Dermatophagoides spp. allergens: murine immune
      response, epitope analysis, and development of a two-site ELISA.
AB  - BACKGROUND: Group II allergens are a major cause of sensitization in patients
      allergic to mites. To facilitate the antigenic analysis of group II allergens and
      to develop improved methods of allergen detection, we compared IgG anti-group II
      antibody responses in inbred mouse strains and raised a panel of monoclonal
      antibodies (mAbs). METHODS: IgE antibody responses were compared by antigen
      binding radioimmunoassay. Epitope specificity of the mAbs was analyzed by two
      site binding assays and by cross-inhibition radioimmunoassays. RESULTS:
      Comparison of polyclonal IgG antibody responses in five BALB congenic strains
      showed that H-2d mice had poor responses, whereas H-2b and H-2k mice had strong,
      cross-reactive, IgG anti-group II responses. The specificities of nine anti-Der p
      II IgE mAbs raised in A/J mice were compared with specificities of seven mAbs
      produced previously. Most mAbs (11 of 16) recognized common epitopes on Der p II
      and Der f II: three were specific to Der p II, and two showed high binding to Der
      f II. Epitope analysis showed that the mAbs defined four cross-reactive,
      nonoverlapping sites on the group II allergens. Binding of several combinations
      of mAbs was compared, and a two-site ELISA for group II antigens was developed.
      Linear regression analysis showed an excellent correlation between results of
      this assay and group II radioimmunoassay of house dust samples (n = 40, r = 0.85,
      p < 0.001). CONCLUSIONS: There are multiple cross-reactive B-cell epitopes on
      group II allergens. The group II ELISA has several important applications,
      including assessment of environmental allergen exposure, monitoring of the
      efficacy of avoidance procedures, and standardization of commercial mite allergen
      extracts.

PMID- 7521894
TI  - The effects of immunosuppressive agents on plasma lipoproteins after organ
      transplantation.

PMID- 7521897
TI  - Sulfated polyanions prevent HIV infection of lymphocytes by disruption of the CD4
      gp120 interaction, but do not inhibit monocyte infection.
AB  - Sulfated polyanions (SPs) bind variably to lymphocyte-expressed CD4 and inhibit
      binding of monoclonal antibodies to the first two domains of CD4. To further
      define this interaction, soluble recombinant CD4 (sCD4; four extracellular
      domains), its truncated amino-terminal two-domain derivative, and three linear
      peptide analogues spanning residues 6-60 (6-24, 20-40, 41-60) in the first domain
      were investigated for SP binding. Dextran sulfate (DXS) (500 kDa), polyvinyl
      sulfate, fucoidan, and carrageenan-kappa, each immobilized on carboxymethyl
      cellulose fibers, bound strongly to both the two-domain and four-domain
      recombinant CD4 molecules (similar to that observed with native CD4), whereas
      dextran sulfate (5 kDa), chondroitin 6-sulfate, and pentosan sulfate bound
      relatively poorly. No peptide binding to SPs was observed. Recombinant gp120
      bound poorly (< 10%) to all of the immobilized polyanions, except pentosan
      sulfate (17%), for which some binding was noted. Binding of radiolabeled V3 loop
      peptide to SPs was slightly greater, with 20-30% binding to polyvinyl sulfate,
      dextran sulfate (500 kDa), and pentosan sulfate. Competitive binding studies
      demonstrated the predominance of sCD4 rather than rgp120 binding to SPs and
      supported previous data demonstrating a binding site for DXS (500 kDa) on the
      first domain of CD4 adjacent to the gp120 binding site and recognized by OKT4C
      and E monoclonal antibodies. Hence disruption of the CD4-gp120 interaction is
      probably responsible for most of the observed antiviral activity of SPs toward
      HIV infection of lymphocytes. However, HIV infection and gp120 binding to
      monocytes was unaffected by SPs, probably because SPs were unable to block the
      CD4-gp 120 interaction in monocytes.

PMID- 7521898
TI  - Prevalence of antibodies to hepatitis C virus among patients with leprosy in
      several African countries and the Yemen.
AB  - The prevalence of anti-HCV was determined in 1,309 leprosy patients and a control
      group of 1,469 subjects from 6 sub-Saharan African countries and the Yemen. Sera
      found positive by an initial second generation ELISA were subjected to 3
      additional confirmatory tests. The anti-HCV prevalence in leprosy patients (7.1%)
      was significantly higher than in the control group (2.6%). HCV seroprevalence
      increased with age in both the control and leprosy groups. No statistically
      significant difference could be found between anti-HCV prevalence and the several
      clinical forms of leprosy among patients. The results of this study indicate a
      high degree of exposure or chronic carriage of hepatitis C among leprosy
      patients.

PMID- 7521896
TI  - A fluorescence-conjugated immunobinding assay for the detection of P-selectin on
      platelets.
AB  - P-selectin (GMP-140 or PADGEM) is translocated to the plasma membrane of
      platelets after platelet activation. P-selectin, therefore, may be a potential
      marker for evaluating platelet activation. A fluorescence-conjugated
      immunobinding assay (FCIBA) has been developed to detect specifically P-selectin
      on platelets. Platelets were isolated from fresh blood by centrifugation and
      stimulated with various doses of ADP before being fixed with 1% of
      paraformaldehyde. Fixed platelets were incubated with fluorescence-conjugated
      anti-P-selectin monoclonal antibody in the wells of fluoricon microtiter plates,
      and the fluorescence intensity was read on a fluorescence concentration analyzer.
      Once platelets were fixed, the procedures were completed in < 2 hours. The intra
      assay coefficient of variation (CV) was 6.97% (n = 40), the time-based interassay
      CV was 8.11% (n = 16), and the sample-based inter-assay CV was 6.17% (n = 16).
      The FCIBA had an excellent correlation (r = 0.936, p < 0.001) with flow cytometry
      in the measurement of expressed P-selectin in platelets of 20 normal donors.
      Translocation of P-selectin in plasma-suspended platelets in response to
      increasing doses of adenosine diphosphate (ADP) occurred in a dose-dependent
      manner and correlated positively with ADP-induced platelet aggregation in terms
      of both stimulating doses of ADP (r = 0.99, p < 0.01) and time intervals (r =
      0.92, p < 0.05). The findings show that FCIBA is a fast and convenient assay with
      good precision for the determination of P-selectin expression of human platelets.

PMID- 7521895
TI  - Serum lipids and apolipoproteins in liver transplant recipients: a comparative
      study of cyclosporin A and FK 506.
AB  - The immunosuppressive agent cyclosporin A (CsA) is reportedly associated with
      clinically adverse effects on circulating lipid and apolipoprotein
      concentrations. To date few data have been reported concerning the effects on
      lipid metabolism of the new macrolide immunosuppressive agent FK 506, and no
      comparative studies of the effects of these drugs have been performed. In
      consideration of the pivotal role of the liver in lipid metabolism, we measured
      fasting serum lipids and apolipoproteins a median of 8 (range 5 to 9) months
      after the operation in 20 clinically stable liver transplant recipients randomly
      allocated to maintenance immunosuppression with CsA +/- azathioprine (n = 10) or
      FK 506 (n = 10). To avoid the confounding effects of corticosteroids on lipid
      metabolism, prednisolone was withdrawn at least 6 weeks beforehand in each case.
      Ten healthy volunteers matched for age and body mass index served as control
      subjects. Serum total cholesterol concentration was significantly lower in both
      the CsA (p < 0.001) and FK 506 (p < 0.05) treatment groups when compared with the
      healthy control subjects. Serum high-density lipoprotein (HDL) cholesterol
      concentration was also significantly lower in both the CsA (p < 0.005) and FK 506
      (p < 0.01) treatment groups. Neither the ratio of serum total cholesterol to HDL
      cholesterol nor the fasting triglyceride concentrations were significantly
      different (p > 0.1) from those of the healthy control subjects for either
      transplant group. Serum apolipoprotein B level was lower than that of the control
      group in both the CsA (p < 0.005) and FK 506 groups (p = 0.06).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7521900
TI  - Use of confirmatory assays for diagnosis of hepatitis C viral infection in
      patients with hepatocellular carcinoma.
AB  - Serum samples from 87 patients with hepatocellular carcinoma (HCC) in the United
      States were tested for evidence of hepatitis C viral (HCV) infection using an
      immunoblot assay for antibodies to the hepatitis C virus and the polymerase chain
      reaction to detect HCV RNA. The findings with these assays were compared to those
      with a first generation enzyme-linked immunoassay (EIA). Antibody to HCV (anti
      HCV) was detected in 14 patients (16%) by EIA; only eight of these were also
      positive by immunoblot and four had HCV RNA by reverse transcription polymerase
      chain reaction (RT-PCR). An additional four cases, negative by EIA, were found to
      be positive by immunoblot; two of these had HCV RNA in serum. Evidence of
      previous hepatitis B viral infection was noted in 15 patients (17%). Only two
      patients with antibody to hepatitis B core antigen also had anti-HCV by the
      immunoblot assay, suggesting that concomitant infection with the hepatitis B and
      C viruses was not common. Thus, HCV infection appears to play a less important
      role in the pathogenesis of HCC in the United States than in southern Europe and
      Japan and other etiologic factors should be sought in this population.

PMID- 7521899
TI  - Locations of antibody binding sites within conserved regions of the hepatitis C
      virus core protein.
AB  - The binding sites for human antibodies recognising antigenic domains within the
      hepatitis C virus (HCV) core protein were analyzed using synthetic peptides.
      Omission peptide analogues where a pair of residues was sequentially omitted were
      produced corresponding to the regions 1-18, 11-28, 21-38, 51-68, and 101-118. The
      N-terminal part of HCV core was found to contain three distinct antibody binding
      sites, which includes the previously reported one at residues 9-16. The other two
      were located at residues 19-26 and residues 29-34. Within the region 51-68 two
      overlapping sites were found, the first at residues 51-60 and the second at
      residues 59-68. Within the region 101-118, residues 107-114 were identified as
      the binding site, which contains two residues differing between genotypes I/II
      and III/VI. Thus the HCV core protein contains at least six distinct linear
      antibody binding sites, located at regions highly conserved between the genotypes
      of HCV. The human recognition of these regions show a variation with respect to
      the amino- and carboxy-terminal extension of each individual binding site. These
      findings will have implications for the prediction of the structure of the HCV
      core protein, since these antibody binding sequences are likely to be more or
      less accessible from the exterior of either, or both, of the native HCV core and
      its precursor polyprotein.

PMID- 7521901
TI  - Clinical significance of hepatitis C antibodies in blood donors.
AB  - The clinical significance of hepatitis C antibodies (anti-HCV) in a healthy
      population was studied by liver function tests and liver biopsies. The patient
      population consisted of 195 (96.1%) of the 203 blood donors found to be either
      anti-HCV positive or indeterminate by a recombinant immunoblot assay (RIBA)
      during the first year of anti-HCV screening of 307,606 donors in Finland using a
      first generation enzyme-linked immunosorbent assay. Alanine aminotransferase
      (ALT) levels in 67 donors reacting positively and in 128 reacting indeterminately
      by a second generation RIBA (RIBA-4) were monitored to evaluate the prevalence of
      liver damage. Serum N-terminal type III procollagen (PIIINP) concentrations were
      measured in all donors who fulfilled our criterion for possible hepatitis C (ALT
      values over two times the normal upper limit on two occasions or over five times
      the normal upper limit on one occasion) and in 23 randomly selected RIBA-4
      positive donors without ALT abnormalities (control group). Two (1.6%) of the RIBA
      4 indeterminate donors had ALT values compatible with possible hepatitis C
      (negative by polymerase chain reaction) whereas there were 25 (37.3%) such
      individuals among the RIBA-4 positive donors (P < 0.0005). Twenty (80%) of the
      latter 25 RIBA-4 positive donors with possible hepatitis C consented to liver
      biopsy. Of these 20 donors, 11 (55.0%) were found to have chronic persistent
      hepatitis, four (20.0%) mild, three (15.0%) moderate, and two (10.0%) severe
      chronic active hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7521902
TI  - Highly sensitive detection of viral RNA genomes in blood specimens by an
      optimized reverse transcription-polymerase chain reaction.
AB  - A protocol was developed for a highly sensitive detection of viral RNA in blood
      specimens by reverse transcription coupled with a nested polymerase chain
      reaction. Using Japanese encephalitis virus (JEV) as a model, the optimized
      reverse transcription-polymerase chain reaction (ORTPCR) detects as few as 3-5
      virions in 0.1 ml of whole blood specimens. The effectiveness of this assay
      system is confirmed by diagnosis of human hepatitis C viral (HCV) infection.

PMID- 7521903
TI  - Differential expression of ICAM-1, VCAM-1 and their ligands LFA-1, Mac-1, CD43,
      VLA-4, and MHC class II antigens in murine Toxoplasma encephalitis: a light
      microscopic and ultrastructural immunohistochemical study.
AB  - Light microscopic and ultrastructural immunohistochemistry of cell adhesion
      molecules (CAMs) and major histocompatibility class II antigens (Ia) expression
      in experimental murine Toxoplasma encephalitis (TE) revealed a prominent
      upregulation of the intercellular cell adhesion molecule-1 (ICAM-1) and of Ia on
      cerebral endothelia, microglia, ependyma, and choroid plexus epithelium during
      acute and chronic TE. Microglia also expressed Mac-1 and leukocyte function
      associated antigen-1 (LFA-1), which are both ligands of ICAM-1, as well as CD45.
      The prominent simultaneous expression of a multitude of these molecules on
      microglia is indicative of a central immunologic function of this cell type in
      TE. Additionally, occasional astrocytic processes slightly expressed Ia in full
      blown TE. The vascular cell adhesion molecule-1 (VCAM-1) was restricted to
      endothelia of cerebral blood vessels, which frequently showed perivascular
      cuffing of inflammatory cells, ependyma, and choroid plexus epithelium.
      Upregulation of Ia, CAMs and their ligands correlated with disease activity.
      Immunohistochemical analysis of the functional state of infiltrating T cells
      showed a preferential recruitment of CD44+ memory and activated interleukin-2R+ T
      cells in TE.

PMID- 7521904
TI  - Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis
      (Dutch). An immunohistochemical study.
AB  - In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) beta/A4
      amyloid deposition is found in meningocortical blood vessels and in diffuse
      plaques in the cerebral cortex. Diffuse plaques putatively represent early stages
      in the formation of senile plaques. Microglia are intimately associated with
      congophilic plaques in Alzheimer's disease (AD), but microglial involvement in
      diffuse plaque formation is controversial. Therefore, we studied the relationship
      between microglia and diffuse plaques in the cerebral cortex of four patients
      with HCHWA-D using a panel of macrophage/microglia markers (mAbs LCA, LeuM5,
      LeuM3, LN3, KP1, OKIa, CLB54, Mac1, Ki-M6, AMC30 and the lectin RCA-1). Eight AD
      patients, one demented Down's syndrome (DS) patient and four non-demented
      controls were included for comparison. In controls and HCHWA-D patients ramified
      or "resting" microglia formed a reticular array in cortical gray and subcortical
      white matter. Microglial cells in or near HCHWA-D diffuse plaques retained their
      normal regular spacing and ramified morphology. In AD/DS gray matter more
      microglial cells were stained than in controls and HCHWA-D patients. Intensely
      immunoreactive microglia with enlarged cell bodies and short, thick processes
      clustered in congophilic plaques. In contrast to the resting microglia, these
      "activated microglia" strongly expressed class II major histocompatibility
      complex antigen, HLA-DR, and were AMC30-immunoreactive. These findings support
      the view that microglia play a role in the formation of congophilic plaques but
      do not initiate diffuse plaque formation. Another finding in this study is the
      presence of strong monocyte/macrophage marker immunoreactivity in the wall of
      cortical congophilic blood vessels in HCHWA-D.

PMID- 7521906
TI  - Doxorubicin and cisplatin with granulocyte colony-stimulating factor as adjuvant
      chemotherapy for osteosarcoma: phase II trial of the European Osteosarcoma
      Intergroup.
AB  - PURPOSE: This report describes the toxicity and feasibility of administering
      doxorubicin (DOX) and cisplatin (CDDP) at 2-week intervals with granulocyte
      colony-stimulating factor (G-CSF) to patients with osteosarcoma and the
      compatibility of this regimen with endoprosthetic surgery performed after three
      cycles. PATIENTS AND METHODS: Twenty-four patients with biopsy-proven
      osteosarcoma were treated with three preoperative cycles of DOX 25 mg/m2/d on
      days 1 to 3 and CDDP 100 mg/m2 on day 1 with G-CSF 5 micrograms/kg/d on days 4 to
      14. Surgery was scheduled at week 6 to be followed by three further cycles of
      chemotherapy at 2-week intervals. RESULTS: Two-week chemotherapy was feasible,
      but delays and dose reductions only allowed 74% and 78% of the intended dose
      intensity of DOX and CDDP to be administered. Thrombocytopenia accounted for 50%
      of delays. Significant toxicity included neutropenic sepsis, severe mucositis,
      prolonged nausea and vomiting, and electrolyte disturbances. Twenty-one limb
      salvage procedures and one amputation were performed. There were eight episodes
      of excessive perioperative bleeding. CONCLUSION: Intensive 2-week chemotherapy
      with intercurrent surgery is feasible and allows a greater dose-intensity of
      chemotherapy to be administered compared with the same regimen administered at 3
      week intervals without G-CSF. The toxicity is considerable, but manageable.

PMID- 7521907
TI  - Randomized study of recombinant human granulocyte colony-stimulating factor after
      high-dose chemotherapy and autologous bone marrow transplantation for high-risk
      lymphoid malignancies.
AB  - PURPOSE: The aim of this prospective randomized trial was to examine the efficacy
      and safety of filgrastim after high-dose chemotherapy and autologous bone marrow
      transplantation (ABMT). PATIENTS AND METHODS: Patients with poor-risk non
      Hodgkin's lymphoma or relapsed Hodgkin's disease were treated in a randomized,
      open-label trial to study the use of filgrastim as an adjunct to high-dose
      chemotherapy and ABMT. Of 43 assessable patients, 19 were randomized to receive
      filgrastim by continuous subcutaneous infusion at a dose of 10 micrograms/kg/d,
      10 to filgrastim 20 micrograms/kg/d, and 14 to a parallel control group that
      received no filgrastim after ABMT. RESULTS: For all filgrastim-treated patients
      analyzed together, the median time to neutrophil recovery > or = 0.5 x 10(9)/L
      after the day of ABMT was significantly accelerated to 10 days compared with 18
      days in control patients (P = .0001). The median number of platelet transfusions
      was identical in both groups. Clinical parameters, including the median number of
      days with fever (1 v 4, P = .0418) and neutropenic fever (5 v 13.5, P = .0001)
      were significantly shorter in the filgrastim than in the control group. The
      number of days on intravenous antibiotics and duration of hospitalization were
      also shorter in the treated groups; however, the differences did not reach
      statistical significance. For patients treated with the two different dose levels
      of filgrastim, the neutrophil recovery and clinical results were similar.
      Filgrastim-associated toxicity appeared to be minimal, with five adverse events
      considered at least possibly related to filgrastim: two in the higher-dose group
      and three in the lower-dose group. All of these were rated moderate, except one
      case of severe bone pain that did not preclude continued filgrastim treatment at
      a lower dose. Survival and relapse-free survival were similar for control and
      filgrastim-treated patients. CONCLUSION: Taken together, the results of this
      first randomized study support the role of filgrastim given as an adjunct to ABMT
      in accelerating neutrophil recovery, as well as in reducing treatment-related
      morbidity and overall duration of the treatment procedure.

PMID- 7521905
TI  - Phase I and pharmacologic study of irinotecan and etoposide with recombinant
      human granulocyte colony-stimulating factor support for advanced lung cancer.
AB  - PURPOSE: We conducted a phase I trial of irinotecan (CPT-11), a topoisomerase I
      inhibitor, combined with etoposide, a topoisomerase II inhibitor, and recombinant
      human granulocyte colony-stimulating factor (rhG-CSF) support because of the
      overlapping neutrophil toxicity of both drugs. The aim was to determine the
      maximum-tolerated dose of CPT-11 combined with a fixed dose of etoposide in
      patients with advanced lung cancer, as well as the dose-limiting toxicities of
      this combination. PATIENTS AND METHODS: Twenty-five patients with stage III or IV
      lung cancer, 15 (60%) with prior chemotherapy, were treated at 4-week intervals
      using CPT-11 (90-minute intravenous infusion on days 1, 8, and 15) plus etoposide
      (80 mg/m2 intravenously on days 1 to 3). In addition, rhG-CSF (2 micrograms/kg/d)
      was given from day 4 to day 21, except on the days of CPT-11 administration. The
      starting dose of CPT-11 was 60 mg/m2, and it was escalated in 10-mg/m2 increments
      until the maximum-tolerated dose was reached. RESULTS: The maximum-tolerated dose
      of CPT-11 was 90 mg/m2, since two of the three patients developed grade 3 to 4
      leukopenia or grade 3 to 4 diarrhea during the first cycle of treatment at this
      dose level. Diarrhea and leukopenia were the dose-limiting toxicities, while
      thrombocytopenia was only a moderate problem. Elimination of CPT-11 was biphasic,
      with a mean +/- SD beta half-life of 18.17 +/- 9.09 hours. The mean terminal half
      life of 7-ethyl-10-hydroxycamptothecin (SN-38; the major metabolite of CPT-11)
      was 43.40 +/- 37.84 hours. There was one complete response (5%) and eight partial
      responses (38%) among 21 assessable patients, for an overall response rate of
      43%. The response rates for small-cell lung cancer (SCLC) and non-small-cell lung
      cancer (NSCLC) were 58% (seven of 12 patients) and 22% (two of nine patients),
      respectively. CONCLUSION: The combination of CPT-11 and etoposide with rhG-CSF
      support seems to be active against lung cancer, especially SCLC, with acceptable
      toxicity. The recommended dose for phase II studies in previously untreated
      patients is 80 mg/m2 of CPT-11 (days 1, 8, and 15) and 80 mg/m2 of etoposide
      (days 1 to 3) plus 2 micrograms/kg of rhG-CSF (days 4 to 21, except when CPT-11
      is given). In addition, 70 mg/m2 of CPT-11 appears to be the appropriate dose for
      previously treated patients receiving this regimen.

PMID- 7521908
TI  - Pharmacologic-guided trial of sequential methotrexate and thioguanine in children
      with advanced malignancies.
AB  - PURPOSE: Based on in vitro studies that have shown synergistic effects of
      sequential administration of methotrexate (MTX) and thioguanine (6-TG), we
      conducted a pharmacologically guided trial of sequential MTX and 6-TG to
      determine the following: (1) the maximum-tolerated dose (MTD) of 6-TG; (2) the
      nature of the dose-limiting toxicity; and (3) the modulation effect of MTX on 6
      TG given by this sequence and schedule. PATIENTS AND METHODS: Thirty-one children
      with advanced malignancies (acute leukemia, n = 10; lymphoma n = 10; and solid
      tumors, n = 11) were treated weekly for 3 weeks with a 2-week rest; treatment
      consisted of a fixed dose of MTX (30 mg/m2 over 24 hours) followed by a 2-hour
      infusion of 6-TG in escalating doses. RESULTS: Measurement of plasma MTX, 6-TG,
      and mononuclear 5-phosphoribosyl-1-pyrophosphate (PRPP) levels indicates that the
      desired biochemical modulation and serum levels were achieved. Nonhematologic
      toxicities were mild and the dose-limiting toxicity was bone marrow depression. A
      300-mg/m2 dose of 6-TG with MTX is considered the MTD. Responses were noted in
      patients with lymphoma. CONCLUSION: Encouraging antitumor effects were produced
      with this regimen in heavily pretreated patients with lymphoma, particularly
      Hodgkin's disease (HD). The durations of responses were 17, 13+, 12, 9, and 7+
      months. A phase II trial of the MTX/6-TG combination is warranted for the
      treatment of relapsed lymphoma.

PMID- 7521909
TI  - Target dependence of adult neurons: pattern of terminal arborizations.
AB  - During development, the survival of neurons in the CNS depends critically on
      interactions with postsynaptic target cells. The role of target cells on the
      maintenance of afferent neurons in the adult, however, is a matter of
      controversy. Morphological alterations of target-deprived neurons, such as axonal
      retraction or pruning, may occur. We have therefore undertaken an analysis of
      target-deprived neurons over time after an excitotoxic lesion in order to
      investigate these potential changes. Dorsal column nuclei (DCN) neurons were
      deprived of their target neurons in adult rats by the injection of kainic acid
      into the ventrobasal thalamic complex. Anterogradely transported wheat germ
      agglutinin conjugated to HRP from the DCN showed a progressive decrease of the
      density of afferent terminals during the first month after lesion. Density
      stabilized thereafter through the longest time studied (8 months). In contrast,
      the extent of the area occupied by DCN projections did not change up to 1 month
      and then shrank over time. These results indicated a continuous decrease in the
      number of axonal elements in the lesion, which is the strongest during the first
      month postlesion. To interpret these data, we then studied axonal morphology.
      Diffusion-filled lemniscal axons were labeled by WGA-HRP injections aimed at the
      medial lemniscus. There was no conspicuous alteration of axonal stems in the
      medial lemniscus. Terminal axonal arborizations and swellings dramatically
      decreased in number over the first month after the kainate injection, and large
      axonal varicosities were formed over the same period of time. These morphological
      data suggest that the decrease in number of axons in an excitotoxic lesion is
      related, at least during the first month, to a loss of axonal terminal
      arborizations rather than to a retraction of axonal stems. The pattern of
      terminal arborizations in the adult CNS may therefore depend critically on
      interactions of afferents with their target neurons, while the maintenance of the
      axonal stems does not.

PMID- 7521910
TI  - Ethanol directly modulates gating of a dihydropyridine-sensitive Ca2+ channel in
      neurohypophysial terminals.
AB  - Ingestion of ethanol results in a decreased level of plasma vasopressin, which
      appears to be caused by inhibition of arginine vasopressin (AVP) release from the
      neurohypophysis. Activation of membrane voltage-gated Ca2+ channels plays an
      important role in triggering this neurohormone release. In this article, single
      channel recordings are used to demonstrate that ethanol, at concentrations
      constituting legal intoxication, inhibits dihydropyridine-sensitive "L-type" Ca2+
      channels in isolated nerve terminals of the rat neurohypophysis. Ethanol reduced
      the channel open probability in a concentration-dependent manner. To allow finer
      resolution of channel openings and to better characterize the mechanisms of
      ethanol action, Bay K 8644 was used to prolong the openings of L-type Ca2+
      channels. In the presence of this dihydropyridine (DHP), the reduction of the
      channel open probability by concentrations of ethanol of 25 mM or higher could be
      determined to be due primarily, although not completely, to a shortening of the
      open duration of this L-channel. Channel conductance was unaffected by ethanol,
      even at high concentrations. These results are consistent with previous
      macroscopic data indicating that calcium channels in these peptidergic terminals
      are targets for ethanol action, and indicate that ethanol acts directly on the
      gating characteristics of the L-type channel. Furthermore, examination of open
      and closed state transitions, as well as Hill plot analysis, suggests that
      ethanol's effects on gating are consistent with the interaction of a single drug
      molecule with a single target site, possibly the L-channel itself.

PMID- 7521911
TI  - Functional comparisons of three glutamate transporter subtypes cloned from human
      motor cortex.
AB  - Reuptake plays an important role in regulating synaptic and extracellular
      concentrations of glutamate. Three glutamate transporters expressed in human
      motor cortex, termed EAAT1, EAAT2, and EAAT3 (for excitatory amino acid
      transporter), have been characterized by their molecular cloning and functional
      expression. Each EAAT subtype mRNA was found in all human brain regions analyzed.
      The most prominent regional variation in message content was in cerebellum where
      EAAT1 expression predominated. EAAT1 and EAAT3 mRNAs were also expressed in
      various non-nervous tissues, whereas expression of EAAT2 was largely restricted
      to brain. The kinetic parameters and pharmacological characteristics of transport
      mediated by each EAAT subtype were determined in transfected mammalian cells by
      radio-label uptake and in microinjected oocytes by voltage-clamp measurements.
      The affinities of the EAAT subtypes for L-glutamate were similar, with Km
      determinations varying from 48 to 97 microM in the mammalian cell assay and from
      18 to 28 microM in oocytes. Glutamate uptake inhibitors were used to compare the
      pharmacologies of the EAAT subtypes. The EAAT2 subtype was distinguishable from
      the EAAT1/EAAT3 subtypes by the potency of several inhibitors, but most notably
      by sensitivity to kainic acid (KA) and dihydrokainic acid (DHK). KA and DHK
      potently inhibited EAAT2 transport, but did not significantly affect transport by
      EAAT1/EAAT3. Using voltage-clamp measurements, most inhibitors were found to be
      substrates that elicited transport currents. In contrast, KA and DHK did not
      evoke currents and they were found to block EAAT2-mediated transport
      competitively. This selective interaction with the EAAT2 subtype could be a
      significant factor in KA neurotoxicity. These studies provide a foundation for
      understanding the role of glutamate transporters in human excitatory
      neurotransmission and in neuropathology.

PMID- 7521913
TI  - Immunohistochemical demonstration of S100 protein in malignant melanomas of the
      facial skin and oral cavity.
AB  - Immunohistochemical demonstration of S100 protein was performed in 56 cases of
      malignant melanoma of the facial skin and oral cavity. The depth of invasion was
      measured comparatively in HE sections and in sections stained for S100 protein.
      Comparison of measured melanoma invasion depth in S100- and HE-stained sections
      revealed a deeper invasion of the tumor in S100-stained slides than in slides
      stained routinely with HE according to Breslow's melanoma staging procedure. A
      reverse relationship between the intensity of immunohistochemical staining for
      S100 protein and survival rate was found in both melanomas of the facial skin and
      oral cavity. Although the presence of S100 protein has been demonstrated
      previously in skin melanomas, no similar investigations concerning the oral
      mucosa have been performed up to now.

PMID- 7521912
TI  - The effects of L-glutamate, AMPA, quisqualate, and kainate on retinal horizontal
      cells depend on adaptational state: implications for rod-cone interactions.
AB  - We studied the responses of isolated and intact luminosity-type horizontal cells
      (L-HC) in the Xenopus retina to L-glutamate (L-glu) and its analogs. Isolated L
      HCs studied with whole-cell patch clamp responded to L-glu, kainate (KA), AMPA,
      or quisqualate (quis) with inward currents from a holding potential of -60 mV,
      associated with a conductance increase. The current elicited by KA was relatively
      large and sustained, whereas AMPA or quis evoked a desensitizing current.
      Coapplication of quis and KA resulted in a smaller current and conductance change
      than that evoked by a pulse of either alone at the same concentration. This
      finding suggests that the L-HC has a single subtype of glutamate receptor that
      responds to both quis and KA. Prior exposure to dopamine enhanced the KA-evoked
      current about twofold. In the superfused eyecup we found that L-HC responses to
      quinoxalinediones (CNQX or DNQX) and to L-glu, KA, AMPA, and quis varied as a
      function of adaptational state. When driven exclusively by either cones or by
      rods, CNQX/DNQX hyperpolarized the L-HC and reduced its light response, without
      altering response kinetics, indicating that both rods and cones communicate with
      L-HCs at ionotropic glutamatergic synapses. Under mesopic conditions, however, as
      CNQX or DNQX reduced cone input, the rod input to the L-HC increased up to
      fivefold in magnitude and had slowed kinetics. The depolarizing response of the L
      HC to L-glu, AMPA, or quis was relatively small and transient under photopic
      conditions, but was much larger and sustained when the eyecup was dark adapted.
      The D1 dopamine antagonist SCH 23390 potentiated the response to quis. In
      contrast, responses to KA were largest in light-adapted eyecups, were potentiated
      by a D1 dopamine agonist, SKF 38393, and were reduced by SCH 23390. We
      hypothesize that the segregated populations of glutamate receptors in the L-HC
      opposite cone and rod synaptic endings can be separately modulated to respond
      differentially to the native transmitter, glutamate. In photopic and mesopic
      states the dominant cone input tonically inhibits rod to L-HC communication. This
      inhibition appears to occur at the postsynaptic membrane and may be mediated by
      second messengers.

PMID- 7521914
TI  - Event and story structure recall by children with specific learning disabilities,
      language impairments, and normally achieving children.
AB  - This study investigated the ability of children with specific learning
      disabilities (SLD), children with language impairments (LI), and children who are
      normally achieving (NA) to recall the events and story structures of a narrative
      and an expository text. Effects of group, verbal age, text structure, and order
      of presentation on recall as measured through listening comprehension were
      studied. Sixty students who were matched on verbal age served as subjects.
      Results suggested differences between the LI and SLD groups on text recall.
      Differences were also evident for text type, with recall of narrative text
      typically being superior to recall of expository text. In general, the
      performance of the group with SLD was similar to that of the NA group.

PMID- 7521917
TI  - Mutational analysis of human papillomavirus E4 proteins: identification of
      structural features important in the formation of cytoplasmic E4/cytokeratin
      networks in epithelial cells.
AB  - We have previously demonstrated that human papillomavirus type 1 (HPV 1) and 16
      (HPV 16) E4 proteins form cytoplasmic filamentous networks which specifically
      colocalize with cytokeratin intermediate-filament (IF) networks when expressed in
      simian virus 40-transformed keratinocytes. The HPV 16 (but not the HPV 1) E4
      protein induced the collapse of the cytokeratin networks. (S. Roberts, I.
      Ashmole, G. D. Johnson, J. W. Kreider, and P. H. Gallimore, Virology 197:176-187,
      1993). The mode of interaction of E4 with the cytokeratin IFs is unknown. To
      identify E4 sequences important in mediating this interaction, we have
      constructed a large panel of mutant HPV (primarily HPV 1) E4 proteins and
      expressed them by using the same simian virus 40-epithelial expression system.
      Mutation of HPV 1 E4 residues 10 to 14 (LLGLL) abrogated the formation of
      cytoplasmic filamentous networks. This sequence corresponds to a conserved motif,
      LLXLL, found at the N terminus of other E4 proteins, and similar results were
      obtained on deletion of the HPV 16 motif, LLKLL (residues 12 to 16). Our findings
      indicate that this conserved motif is likely to play a central role in the
      association between E4 and the cytokeratins. An HPV 1 E4 mutant protein
      containing a deletion of residues 110 to 115 induced the collapse of the
      cytokeratin IFs in a manner analogous to the HPV 16 E4 protein. The sequence
      deleted, DLDDFC, is highly conserved between cutaneous E4 proteins. HPV 1 E4
      residues 42 to 80, which are rich in charged amino acids, appeared to be
      important in the cytoplasmic localization of E4. In addition, we have mapped the
      N-terminal residues of HPV 1 E4 16-kDa and 10/11-kDa polypeptides expressed by
      using the baculovirus system and shown that they begin at tyrosine 16 and alanine
      59, respectively. Similar-sized E4 proteins are also found in vivo. N-terminal
      deletion proteins, which closely resemble the 16-kDa and 10/11-kDa species,
      expressed in keratinocytes were both cytoplasmic and nuclear but did not form
      cytoplasmic filamentous networks. These findings support the postulate that N
      terminal proteolytic processing of the E1-- E4 protein may modulate its function
      in vivo.

PMID- 7521915
TI  - Transcription of the human T-cell lymphotropic virus type I promoter by an alpha
      amanitin-resistant polymerase.
AB  - The human T-lymphotropic virus type I (HTLV-I) promoter contains the structural
      features of a typical RNA polymerase II (pol II) template. The promoter contains
      a TATA box 30 bp upstream of the transcription initiation site and binding sites
      for several pol II transcription factors, and long poly(A)+ RNA is synthesized
      from the integrated HTLV-I proviral DNA in vivo. Consistent with these
      characteristics, HTLV-I transcription activity was reconstituted in vitro by
      using TATA-binding protein, TFIIA, recombinant TFIIB, TFIIE, and TFIIF, TFIIH,
      and pol II. Transcription of the HTLV-I promoter in the reconstituted system
      requires RNA pol II. In HeLa whole cell extracts, however, the HTLV-I long
      terminal repeat also contains an overlapping transcription unit (OTU). HTLV-I OTU
      transcription is initiated at the same nucleotide site as the RNA isolated from
      the HTLV-I-infected cell line MT-2 but was not inhibited by the presence of alpha
      amanitin at concentrations which inhibited the adenovirus major late pol II
      promoter (6 micrograms/ml). HTLV-I transcription was inhibited when higher
      concentrations of alpha-amanitin (60 micrograms/ml) were used, in the range of a
      typical pol III promoter (VA-I). Neutralization and depletion experiments with
      three distinct pol II antibodies demonstrate that RNA pol II is not required for
      HTLV-I OTU transcription. Antibodies to basal transcription factors TATA-binding
      protein and TFIIB, but not TFIIIC, inhibited HTLV-I OTU transcription. These
      observations suggest that the HTLV-I long terminal repeat contains overlapping
      promoters, a typical pol II promoter and a unique pol III promoter which requires
      a distinct set of transcription factors.

PMID- 7521916
TI  - Effects of alterations of primer-binding site sequences on human immunodeficiency
      virus type 1 replication.
AB  - The human immunodeficiency virus type 1 genomic RNA primer-binding site (PBS)
      sequence comprises 18 nucleotides which are complementary to those at the 3' end
      of the replication initiation primer tRNA(3Lys). To investigate the role of the
      PBS in viral replication, we either deleted the original wild-type PBS
      (complementary to tRNA(3Lys) or replaced it with DNA sequences complementary to
      either tRNA(1,2Lys) or tRNA(Phe). Transfection of COS cells with such molecular
      constructs yielded similar levels of viral progeny that were indistinguishable
      with regard to viral proteins and tRNA content. Virus particles derived from PBS
      deleted molecular clones were noninfectious for MT-4, Jurkat, and CEM-T4 cells.
      However, infectious viruses were derived from constructs in which the PBS had
      been altered to sequences complementary to either tRNA(1,2Lys) or tRNA(Phe),
      although mutated forms showed significant lags in replication efficiency in
      comparison with wild types. Molecular analysis of reverse-transcribed DNA in
      cells infected by the mutated viruses indicated that both tRNA(1,2Lys) and
      tRNA(Phe) could function as primers for reverse transcription during the early
      stages of infection. Sequencing of full-length proviral DNA, obtained 6 days
      after infection, revealed the mutated PBS, indicating that a complete cycle of
      reverse transcription had occurred. During subsequent rounds of infection,
      reversion of the mutated PBS to wild-type sequences was observed, accompanied by
      increased production of viral gene products. Reversion to wild-type PBS sequences
      was confirmed both by specific PCR analysis, using distinct primer pairs, and by
      direct sequencing of amplified segments. We also performed endogenous in vitro
      reverse transcription experiments in which synthesis of minus-strand strong-stop
      viral DNA was primed from a synthetic RNA template containing a PBS complementary
      to various tRNA isoacceptors. These results showed that tRNA(3Lys) was a much
      more efficient primer of such reactions than either tRNA(1,2Lys) or tRNA(Phe).

PMID- 7521918
TI  - Vaccine-induced neutralizing antibodies directed in part to the simian
      immunodeficiency virus (SIV) V2 domain were unable to protect rhesus monkeys from
      SIV experimental challenge.
AB  - The potential of the simian immunodeficiency virus (SIV) variable 2 (V2) domain
      as an effective region to boost SIV-neutralizing antibodies and to protect
      against live SIV challenge was tested in rhesus macaques. In this study, two
      rhesus macaques were primed with vaccinia virus recombinants expressing the
      surface glycoprotein gp140 of SIVmac and were given booster injections with the
      SIVmac V2 domain presented by a highly immunogenic carrier, the hepatitis B
      surface antigen (HBsAg). The two vaccinated macaques exhibited SIV-neutralizing
      antibodies after primer injections that were enhanced by the V2/HBsAg injections.
      Part of these SIV-neutralizing antibodies were directed specifically to the V2
      region, as shown by neutralization-blocking experiments. However, despite having
      consistent SIV-neutralizing antibody titers, animals were not protected against
      homologous challenge with BK28, the molecular clone of SIVmac251. No SIV envelope
      specific cellular cytotoxic response was detected throughout the immunization
      protocol, suggesting that neutralizing antibodies directed to SIV envelope gp140
      and especially to the V2 domain were unable on their own to protect against SIV
      challenge. Furthermore, the vaccinees seemed to have higher viral loads than
      control animals after challenge, raising the question of whether neutralizing
      antibodies induced by vaccination and directed to the SIV envelope selected viral
      escape mutants, as shown previously in SIV-infected macaques. This mechanism is
      certainly worthy of intensive investigation and raises some concern for SIV
      envelope-targeted immunization.

PMID- 7521922
TI  - Kaposi's sarcoma, vascular permeability, and scientific integrity.

PMID- 7521923
TI  - Kaposi's sarcoma, vascular permeability, and scientific integrity.

PMID- 7521920
TI  - Dual tropism for macrophages and lymphocytes is a common feature of primary human
      immunodeficiency virus type 1 and 2 isolates.
AB  - We have investigated the ability of human immunodeficiency virus type 1 (HIV-1)
      and HIV-2 isolates to infect and replicate in primary human macrophages.
      Monocytes from blood donors were allowed to differentiate into macrophages by
      culture in the presence of autologous lymphocytes and human serum for 5 days
      before infection. A panel of 70 HIV-1 and 12 HIV-2 isolates were recovered from
      seropositive individuals with different severities of HIV infection. A majority
      of isolates (55 HIV-1 and all HIV-2) were obtained from peripheral blood
      mononuclear cells, but isolates from cerebrospinal fluid, monocytes, brain
      tissue, plasma, and purified CD4+ lymphocytes were also included. All isolates
      were able to infect monocyte-derived macrophages, even though the replicative
      capacity of the isolates varied. Interestingly, isolates with a rapid/high,
      syncytium-inducing phenotype did not differ from slow/low, non-syncytium-inducing
      isolates in their ability to replicate in monocyte-derived macrophages. Others
      have reported that rapid/high, syncytium-inducing isolates have a reduced ability
      to infect and replicate in monocytes. However, different methods to isolate and
      culture the monocytes/macrophages were used in these studies and our study. Thus,
      the ability of HIV isolates to replicate in monocytes/macrophages appears to be
      strongly influenced by the isolation and culture procedures. It remains to be
      determined which culture procedure is more relevant for the in vivo situation.

PMID- 7521924
TI  - [Effects of laser irradiation of blood on electrical ventricular instability in
      patients with progressive angina pectoris].
AB  - The impact of laser blood irradiation (LBI) on electrical instability has been
      studied in 71 patients with progressive angina pectoris. The amount of couplets
      of ventricular premature beats after LBI was decreased, as evidenced by 24-hour
      monitoring. Invasive programmed ventricular stimulation provided better
      electrophysiological properties of the myocardium after LBI: primary examination
      showed that electrical ventricular instability was detected in 40%, but after the
      therapy it was only in 20% patients. Thus, LBI is an effective tool to decrease
      electrical ventricular instability, a major risk factor for sudden coronary death
      in patients with progressive angina pectoris.

PMID- 7521926
TI  - Gradual emergence of developmental language disorders.
AB  - This article presents a theory of normal and delayed development of language.
      According to the theory, linguistic capacity develops in critically timed phases
      that occur gradually and sequentially. Normally, the rapid accumulation of stored
      utterances activates analytical mechanisms that are needed for the development of
      linguistic grammar. Children with slowly developing brains have delays in the
      socially cognitive systems that store utterances, and a critical period for
      activation of experience-dependent grammatical mechanisms declines without
      optimal result. Continuing efforts to speak induct species-atypical allocations
      of neural resources into linguistic service. It is speculated that this
      compensatory activity leads to compensatory growth, which may ultimately be
      revealed as volumetric symmetry of perisylvian areas. Because rate of brain
      maturation is under genetic as well as environmental control, the stage is thus
      set for an impairment that will seem to be specific and a brain that will appear
      to be abnormal.

PMID- 7521925
TI  - [Endolymphatic drug infusion in the treatment of complicated acute appendicitis].
AB  - The work is based on lymphogenous methods of treatment, i.e. direct endolymphatic
      therapy with antibiotics and other agents in complications of acute appendicitis.
      On the basis of information in the literature, among the antibiotics we chose
      gentamicin, claforan, and a new antibiotic fortum. In addition to antibiotics,
      for the correction of disturbed blood rheological properties we gave
      endolymphatic infusions of trasylol, aspisol, and trental. The purpose of our
      study was the development of methods and treatment of complications of acute
      appendicitis. In view of this, we chose the patients according to the nosological
      groups with appendicular infiltrate, appendicular abscesses, and localized
      peritonitis of appendicular origin.

PMID- 7521919
TI  - Efficient particle formation can occur if the matrix domain of human
      immunodeficiency virus type 1 Gag is substituted by a myristylation signal.
AB  - Lentiviruses, such as human immunodeficiency virus type 1 (HIV-1), assemble at
      and bud through the cytoplasmic membrane. Both the matrix (MA) domain of Gag and
      its amino-terminal myristylation have been implicated in these processes. We have
      created HIV-1 proviruses lacking the entire matrix domain of gag which either
      lack or contain an amino-terminal myristate addition sequence at the beginning of
      the capsid domain. Myristate- and matrix-deficient [myr(-)MA(-)] viruses produced
      after transient transfection are still able to assemble into particles, although
      the majority do not form at the plasma membrane or bud efficiently. Myristylation
      of the amino terminus of the truncated Gag precursor permits a much more
      efficient release of the mutant virions. While myr(-)MA(-) particles were
      inefficient in proteolytic processing of the Gag precursor, myristylation enabled
      efficient proteolysis of the mutant Gag. All matrix-deficient viruses are
      noninfectious. Particles produced by matrix-deficient mutants contain low levels
      of glycoproteins, indicating the importance of matrix in either incorporation or
      stable retention of Env. Since matrix-deficient viruses contain a normal
      complement of viral genomic RNA, a role for MA in genomic incorporation can be
      excluded. Contrary to previous reports, the HIV-1 genome does not require
      sequences between the 5' splice donor site and the gag start codon for efficient
      packaging.

PMID- 7521921
TI  - A simian immunodeficiency virus envelope V3 cytotoxic T-lymphocyte epitope in
      rhesus monkeys and its restricting major histocompatibility complex class I
      molecule Mamu-A*02.
AB  - The use of the simian immunodeficiency virus (SIV) macaque model for assessing
      human immunodeficiency virus vaccine strategies will be facilitated by the
      characterization of predominant SIV cytotoxic T-lymphocyte (CTL) epitopes and
      their restricting major histocompatibility complex (MHC) class I molecules in
      macaque species. We now define a rhesus monkey SIVmac CTL epitope in the third
      hypervariable region of the envelope glycoprotein of the virus. This epitope,
      YNLTMKCR, contains the first two amino acids of a cysteine-cysteine loop which is
      the SIVmac analog of the human immunodeficiency virus type 1 V3 loop. We also
      employed one-dimensional isoelectric focusing to characterize the MHC class I
      molecule of the rhesus monkey that binds this SIVmac envelope peptide fragment.
      Cloning and sequencing the cDNA encoding this rhesus monkey MHC class I molecule
      demonstrates that it is a newly described HLA-A homolog, Mamu-A*02. This viral
      CTL epitope and its restricting MHC class I molecule will facilitate the use of
      the SIVmac rhesus monkey model for studies of envelope-based vaccine strategies
      and for exploring AIDS immunopathogenesis.

PMID- 7521927
TI  - Partial remission of parotid gland carcinoma after goserelin.

PMID- 7521928
TI  - Interaction between tacrolimus and erythromycin.

PMID- 7521929
TI  - Effect of electrical tooth stimulation on blood flow, interstitial fluid pressure
      and substance P and CGRP-immunoreactive nerve fibers in the low compliant cat
      dental pulp.
AB  - The effect of vasodilation on simultaneously measured interstitial fluid pressure
      (IFP, micropuncture) and blood flow (laser-Doppler) in the low compliant pulpal
      connective tissue was investigated in 10 cats. Vasodilation was induced by
      electrical stimulation of the tooth after pretreatment with the sympathetic
      blocker guanethidine. Visualization of the sensory neuropeptides calcitonin gene
      related peptide (CGRP) and substance P (SP) was performed using
      immunocytochemistry. The study was designed to answer the following questions.
      (1) Does vasodilation promptly increase IFP in low compliant tissues? (2) Does an
      increase in IFP counteract the blood flow increase? (3) Does repeated electrical
      stimulation cause reduced staining of CGRP- and SP-immunoreactive nerve fibers in
      the dental pulp? Electrical stimulation resulted consistently in a nearly
      synchronous increase in both blood flow and IFP. IFP was nearly doubled, from 6.3
      +/- 0.18 mm Hg in control to 11.7 +/- 0.44 mm Hg, whereas blood flow increased by
      28%. However, despite continued vasodilation the IFP fell to control level, or
      even lower, within 1-5 min. The results indicate that the increased IFP will
      promote fluid absorption into the blood, counteracting a further IFP increase in
      low compliant tissues during vasodilation. Accordingly, transmural pressure is
      only transitorily reduced and compression of vessels does not take place. There
      was considerably less CGRP- and SP-immunoreactive fibers in the stimulated teeth
      than in the contralateral controls, suggesting that the vasodilation was caused
      by liberation of these sensory neuropeptides.

PMID- 7521930
TI  - Regional differences in spontaneously occurring angiogenesis in the adult rat
      mesentery.
AB  - Despite intensive study in the area of angiogenesis, relatively little is known
      about normal angiogenesis in adult animals. Preliminary studies using the
      Griffonia simplicifolia I (GSI) lectin as a microvascular marker indicated that
      capillary sprouting occurs in the clear "windows" of normal intact adult rat
      mesentery. The purpose of this study was to determine whether angiogenesis occurs
      uniformly within the mesenteric windows and whether maturational age affects the
      extent of angiogenesis in the absence of any experimental or pathological
      perturbation. Four groups of female Sprague-Dawley rats were used, "weanling" (4
      5 weeks), "juvenile" (6-8 weeks), "young adult" (10-13 weeks), and "adult" (16-20
      weeks). Microvessels sprouting into proximal and distal windows were delineated
      in whole mounts by use of fluorescent derivative of the GSI lectin. Microvascular
      sprouting, indicating angiogenesis, was found in all age groups, but was most
      frequent in the windows sampled from the distal region of the small intestine
      when compared with those from the proximal region. The mean number of
      microvessels per sample site was significantly higher in the distal windows of
      adults than in the weanling or juvenile rats. Angiogenesis was found to occur
      asymmetrically within the individual windows in the two adult groups, with
      significantly more angiogenesis on the intestinal side compared to that along the
      portal vessels. We conclude that there is an age-related increase in angiogenesis
      into the mesenteric windows, and that the intestinal side is more prone to
      spontaneous angiogenesis than is the portal side.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7521931
TI  - Treatment of malignant testicular tumors in childhood: results of the German
      National Study 1982-1992.
AB  - The German Cooperative Protocol for treatment of testicular germ cell tumors in
      childhood registered 106 patients from January 1982 through February 1992. Sixty
      one patients suffered from yolk sac tumors (YST); 25 patients from differentiated
      teratomas (TD); 19 patients from malignant teratomas of either intermediate
      (MTI), undifferentiated (MTU), or trophoblastic type (MTT), and 1 patient from a
      seminoma. A stratified chemotherapy based on stage and histology was administered
      in addition to unilateral orchiectomy: Standard chemotherapy consisted of four
      treatments with vinblastine, bleomycin, and cisplatinum. If viable tumor was
      suspected after two treatments with standard chemotherapy, a delayed explorative
      laparotomy was done. There were two options based on the histological findings:
      In case of complete tumor regression, the standard chemotherapy was continued. In
      case of incomplete tumor response, patients received a salvage chemotherapy
      consisting of three treatments with VP 16 (etoposide), ifosfamide, and
      cisplatinum. In addition three injections with VP 16 were given as a maintenance
      therapy. The following results were obtained: YST: 59 patients with stage I.
      Forty-nine patients were followed according to "wait and see" policy. Eight of
      these needed a delayed standard chemotherapy. The relapse free survival of all 61
      patients in 100%. Median observation time is 49 months. TD: Twenty-five patients
      had stage I. No chemotherapy was given. The relapse free survival is 100%. Median
      observation time is 48 months. Malignant teratomas (MTI, MTU, MTT): 8 patients
      had stage I. Three of these received adjuvant chemotherapy and 5 lymphadenectomy
      without chemotherapy. All patients survived without relapse. Nine patients had
      stage II and received standard chemotherapy. Four of these patients had a delayed
      explorative laparotomy leading to a salvage therapy in two patients. All patients
      survived relapse free. Two patients had stage III. Of these 1 received standard
      chemotherapy and is well. One patient suffering from MTU stage IIIA died due to
      candida septicemia during salvage therapy. Median observation time of the entire
      group is 60 months.

PMID- 7521932
TI  - [Thymic hyperplasia. Description of a clinical case].
AB  - Thymomegaly, which was in the past considered as predisposition to sudden death
      infants, is judged today as paraphysiological. The study achieved on a 10 months'
      patient shows the complexity in determining the diagnosis of simple thymic
      hyperplasia, when together with a massive thymus enlargement are conditions which
      divert to other pathologies, as in this tested clinical case.

PMID- 7521934
TI  - Restricted variable region gene usage and possible rheumatoid factor relationship
      among human monoclonal antibodies specific for the AD-1 epitope on
      cytomegalovirus glycoprotein B.
AB  - The nucleotide sequences of the variable region genes encoding five different
      human, high affinity antibodies, specific for the major neutralization
      determinant (AD-1) expressed by human cytomegalovirus glycoprotein B (gp58/116),
      have been determined. Three of the five heavy chain variable regions belonged to
      the small VHV-family, although they combined with a diverse set of light chains
      (V kappa IIIb, V lambda II and V lambda III). The other two antibodies belonged
      to VH-families III and IV. One of the VHV-family genes most likely originated
      from a previously unreported germline gene or allele, since it carries a nine
      nucleotide insert in framework 1. In addition, V lambda-genes showed variable
      homology (77-95%) to known germline sequences, while V kappa-genes showed high
      homology (approximately 98%) with their proposed germline origin. Despite the
      close homology of the V kappa IIIb-gene used to express one of the antibodies
      with its corresponding germline gene, the protein did not strongly express some
      idiotypes associated with this light chain family. There is, thus, no direct
      relation between the expression of these crossreactive idiotypes and the use of
      even modestly mutated light chains belonging to this V kappa-family, which has
      been implicated in the development of anti-idiotypic networks possibly inducing
      autoantibodies, such as rheumatoid factors.

PMID- 7521933
TI  - Potential therapeutic recombinant proteins comprised of peptides containing
      recombined T cell epitopes.
AB  - The complete primary structure of Fel d I2 has been determined and shown to be
      comprised of two separate polypeptide chains (designated chain 1 and 2).
      Overlapping peptides covering the entire sequence of both chains of Fel d I have
      been used to map the major areas of human T cell reactivity. The present study
      describes three non-contiguous T cell reactive regions of < 30 aa in length that
      were assembled in all six possible configurations using PCR and recombinant DNA
      methods. These six recombinant proteins comprised of defined non-contiguous T
      cell epitope regions artificially combined into single polypeptide chains have
      been expressed in E. coli, highly purified, and examined for their ability to
      bind to human cat-allergic IgE and for human T cell reactivity. Several of these
      recombined T cell epitope-containing polypeptides exhibit markedly reduced IgE
      binding as compared to the native Fel d I. Importantly, the human T cell
      reactivity to individual T cell epitope-containing regions is maintained even
      though each was placed in an unnatural position as compared to the native
      molecule. In addition, T cell responses to potential junctional epitopes were not
      detected. It was also demonstrated in mice that s.c. injection of T cell epitope
      containing polypeptides inhibits the T cell response to the individual peptides
      upon subsequent challenge in vitro. Thus, these recombined T cell epitope
      containing polypeptides, which harbor multiple T cell reactive regions but have
      significantly reduced reactivity with allergic human IgE, constitute a novel
      potential approach for desensitization to important allergens.

PMID- 7521935
TI  - Genetic toxicity of 2-acetylaminofluorene, 2-aminofluorene and some of their
      metabolites and model metabolites.
AB  - 2-Acetylaminofluorene and 2-aminofluorene are among the most intensively studied
      of all chemical mutagens and carcinogens. Fundamental research findings
      concerning the metabolism of 2-acetylaminofluorene to electrophilic derivatives,
      the interaction of these derivatives with DNA, and the carcinogenic and mutagenic
      responses that are associated with the resulting DNA damage have formed the
      foundation upon which much of genetic toxicity testing is based. The parent
      compounds and their proximate and ultimate mutagenic and carcinogenic derivatives
      have been evaluated in a variety of prokaryotic and eukaryotic assays for
      mutagenesis and DNA damage. The reactive derivatives are active in virtually all
      systems, while 2-acetylaminofluorene and 2-aminofluorene are active in most
      systems that provide adequate metabolic activation. Knowledge of the structures
      of the DNA adducts formed by 2-acetylaminofluorene and 2-aminofluorene, the
      effects of the adducts on DNA conformation and synthesis, adduct distribution in
      tissues, cells and DNA, and adduct repair have been used to develop hypotheses to
      understand the genotoxic and carcinogenic effects of these compounds. Molecular
      analysis of mutations produced in cell-free, bacterial, in vitro mammalian, and
      intact animal systems have recently been used to extend these hypotheses.

PMID- 7521936
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 37-1994. A newborn boy with petechiae, hepatosplenomegaly,
      leukocytosis, and thrombocytopenia.

PMID- 7521937
TI  - A novel mutation in the cystic fibrosis gene in patients with pulmonary disease
      but normal sweat chloride concentrations.
AB  - BACKGROUND: Many patients with chronic pulmonary disease similar to that seen in
      cystic fibrosis have normal (or nondiagnostic) sweat chloride values. It has been
      difficult to make the diagnosis of cystic fibrosis in these patients because no
      associated mutation in the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene has been identified. METHODS: We evaluated 23 patients with pulmonary
      disease characteristic of cystic fibrosis but with sweat chloride concentrations
      in the normal range. Mutations in the CFTR gene were sought by direct sequencing
      of polymerase chain reaction-amplified nasal epithelial messenger RNA and by
      testing the functioning of affected epithelium. RESULTS: A cytidine phosphate
      guanosine dinucleotide C-to-T point mutation in intron 19 of the CFTR gene,
      termed 3849 + 10 kb C to T, was identified in 13 patients from eight unrelated
      families. This mutation was found in patients from three different ethnic groups
      with three different extended haplotypes. The mutation leads to the creation of a
      partially active splice site in intron 19 and to the insertion into most CFTR
      transcripts of a new 84-base-pair "exon," containing an in-frame stop codon,
      between exons 19 and 20. Normally spliced transcripts were also detected at a
      level approximately 8 percent of that found in normal subjects. This mutation is
      associated with abnormal nasal epithelial and sweat acinar epithelial function.
      CONCLUSIONS: We have identified a point mutation in intron 19 of CFTR and
      abnormal epithelial function in patients who have cystic fibrosis-like lung
      disease but normal sweat chloride values. The identification of this mutation
      indicates that this syndrome is a form of cystic fibrosis. Screening for the
      mutation should prove diagnostically useful in this population of patients.

PMID- 7521939
TI  - Images in clinical medicine. Porphyria cutanea tarda.

PMID- 7521938
TI  - Transmissibility of Pseudomonas cepacia infection in clinic patients and lung
      transplant recipients with cystic fibrosis.
AB  - BACKGROUND: In patients with cystic fibrosis, infection with Pseudomonas cepacia
      is associated with poor outcomes. However, the extent of person-to-person
      transmission and the source of P. cepacia infection after lung transplantation
      are not well defined. Using DNA-based typing systems, we sought to determine the
      genetic relatedness of P. cepacia infection at one cystic fibrosis center.
      METHODS: We analyzed 65 P. cepacia isolates gathered over a period of eight years
      at a single cystic fibrosis center from 17 clinic patients and from 5 patients
      who underwent double-lung transplantation. The isolates were analyzed by
      ribotyping and chromosomal fingerprinting based on pulsed-field gel
      electrophoresis. RESULTS: Analyses of serial isolates revealed that each clinic
      patient and transplant recipient harbored a different P. cepacia clone that was
      persistent. In the transplant recipients, the preoperative and postoperative
      isolates were identical. In the two patients with disseminated infection after
      lung transplantation, isolates from multiple sites were identical and indicated
      clonal expansion of the previous respiratory P. cepacia strain. Pulsed-field gel
      electrophoresis proved both more discriminative and more practical than
      ribotyping as a means of defining the genetic relatedness of the P. cepacia
      isolates. CONCLUSIONS: Our serial analyses in patients with cystic fibrosis at
      one center found distinct strains of P. cepacia persistently infecting each
      patient and no evidence of person-to-person transmission of this organism. P.
      cepacia infection after lung transplantation was due to the persistence of the
      strain present before transplantation.

PMID- 7521940
TI  - [Evaluation of treatment efficiency of acute hemispheric strokes using
      intravenous nimodipine infusions].
AB  - The authors present the results of treating acute hemispheric stroke with
      intravenous nimodipine. 17 patients were additionally treated with nimodipine
      given intravenously in 1 mg-2 mg dose, and the control group consisted of 71
      patients treated in standard way with Dextran 40,000. The selection of patients
      for the study was random, and the treatment was conducted by blind trial method.
      All patients were admitted within 24 hours since acute stroke onset. The
      diagnosis was based on clinical examination and CT. The analysis of treatment
      results was made twice before and after the treatment according to criteria
      recommended by WHO Karnofsky scale. Statistical analysis showed that in the group
      treated additionally with nimodipine neurological and social consequences of
      stroke were significantly lower in comparison with standard therapy (p < 0.001).

PMID- 7521941
TI  - [Central nervous system changes in infants with HIV infection. Epidemiology and
      neurology].
AB  - The increase of HIV infected population reaching worldwide 10 million of cases
      leads to a great number of infected women in reproductive age. Finally the
      perinatally acquired HIV infection has become a great problem. The number of
      infants with AIDS is estimated at about 160,000. The diagnosis and evaluation of
      significant clinical symptoms of HIV infection in infants are briefly described
      in this study. The nervous system being one of targets of HIV infection the
      neurological manifestation occurring in infants were more extensively discussed.
      Microencephaly or brain atrophy and psycho-motor developmental delay resulting in
      progressive or static encephalopathy syndromes were presented.

PMID- 7521943
TI  - Effect of cyclosporin and the prostacyclin analogue iloprost on human glomerular
      vasoreactivity.
AB  - Cyclosporin is known to cause a decrease in renal blood flow and glomerular
      filtration rate in both humans and animals. These acute modifications are
      reversible if the drug is withdrawn, and seem to be caused by a local hormonal
      imbalance between vasoconstricting and vasodilating substances. We studied human
      glomeruli incubated with either CsA alone, iloprost alone, or CsA + iloprost.
      Photomicrographs of glomeruli were taken at t0, t1, t2 and t5 min and glomerular
      areas were measured with a videoanalyser linked to a computer. Results show a
      significant vasoconstriction with CsA alone, and no significant modification of
      glomerular areas with iloprost or CsA + iloprost. We conclude that iloprost
      prevents CsA-induced vasoconstriction in human glomeruli in vitro.

PMID- 7521942
TI  - [Neurocysticercosis: benign natural course].
AB  - In a waiter aged 51 without clinical symptoms, but with a history of sporadic
      epileptic seizures in young age, radiological examination demonstrated multiple
      calcifications in the brain corresponding to calcified cysticerci. Similar
      lesions were found in the muscles of the thighs and left lower leg. After another
      18 years without cerebral symptoms these calcifications were demonstrated in CT.
      The case indicates that the natural course of cerebral cysticercosis may be
      asymptomatic or oligosymptomatic, and that it is useful to distinguish between
      active and inactive cysticercosis.

PMID- 7521944
TI  - Abnormally phosphorylated tau protein related to the formation of neurofibrillary
      tangles and neuropil threads in the cerebral cortex of sheep and goat.
AB  - Frontal sections including temporal isocortex, entorhinal region and hippocampus
      from aged domestic animals (dog, cat, horse, sheep and goat) were studied for
      Alzheimer-related changes using immunostaining with the AT8 antibody for
      abnormally phosphorylated tau protein and selective silver techniques for A4
      amyloid and neurofibrillary changes of the Alzheimer type. The material available
      to us did not show A4 amyloid deposits or argyrophilic neurofibrillary changes.
      Only the brains of aged sheep and goat exhibited the presence of AT8
      immunoreactive pyramidal cells in the entorhinal region and hippocampal
      formation. Two groups of AT8-positive neurons could be observed: The first group
      contained evenly distributed immunoreactive material in all parts of the soma,
      the dendrites and the axon. The neuronal processes appeared quite normal. The
      second group, however, showed conspicuous changes in the cellular processes
      consisting of a loss of immunoreactivity within the axon and the proximal
      dendrites and the appearance of intensely stained swellings within the curved
      distal dendrites. These changes were closely reminiscent to alterations of the
      cytoskeleton known to occur at the same location in the aging human brain and in
      Alzheimer's disease. The findings justify a closer look at sheep and goat when
      searching for suitable animal models for experimental studies of the conditions
      responsible for the development of Alzheimer-related neurofibrillary changes.

PMID- 7521945
TI  - Neonatal capsaicin treatment in rats results in scratching behavior with skin
      damage: potential model of non-painful dysesthesia.
AB  - We administered capsaicin or vehicle in 2-day-old rat pups, and for over 6 months
      examined the rats for damaged skin and for the behaviors of scratching, gnawing
      and biting their skin. By 35 days of age, all rats in the capsaicin group (n =
      10) had damaged skin (i.e., lesions, hair loss and red skin) on the rostral half
      of their bodies. Skin damage remained prevalent over 6 months, whereas vehicle
      treated rats (n = 8) had virtually no skin damage. Gnawing and biting behaviors
      were rarely observed, however, rats in the capsaicin group frequently scratched
      themselves. There was a significant positive correlation between the frequency at
      which rats scratched themselves and the total area of skin damage. Morphine (3.0
      mg/kg, i.p.) greatly increased scratching behavior in only the capsaicin-treated
      rats and naloxone (0.5 mg/kg, i.p.) significantly reduced scratching in these
      rats. Thus, neonatal capsaicin, in its destruction of the majority of primary
      afferent C-fibers, is capable of inducing opioid-sensitive scratching behavior.

PMID- 7521946
TI  - Possible role of glutamatergic neurotransmission in regulating ethanol-evoked
      brain ascorbate release.
AB  - It was found that systemic application of ethanol induced brain ascorbate (AA)
      release. In order to study the mechanism of ethanol-evoked AA release, the role
      of brain glutamatergic neurotransmission was investigated using in vivo
      voltammetry in the striatum of freely moving rats. Pretreatment with L-trans
      pyrrolidine-2,4-dicarboxylate (PDC, 10 nmol, i.c.v.), a glutamate (Glu) uptake
      blocker, potentiated ethanol (1 g/kg, intraperitoneal injection, i.p.)-evoked
      release of brain AA. N-methyl-D-aspartate (NMDA, 1 nmol, i.c.v.) produced a fast
      transient increase in extracellular AA, whereas alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA, 1 nmol, i.c.v.) produced a decrease in extracellular
      AA (75.8 +/- 3% of control). Kainate (KA, 1 nmol, i.c.v.) produced an initial
      decrease (48.7 +/- 11.7% of control) then an increase (250 +/- 68.5% of control)
      in extracellular AA. These results suggest that systemic administration of
      ethanol may affect the release or uptake of brain glutamatergic neurotransmitters
      which appear to regulate brain AA release. The NMDA, but not the non-NMDA, type
      of Glu receptor may be responsible for this regulation.

PMID- 7521947
TI  - Nitric oxide synthase in the brain of a teleost.
AB  - The presence and distribution of the nitric oxide (NO) converting enzyme, NO
      synthase (NOS), was investigated in the brain of a teleost, the Atlantic salmon.
      Both NOS immunoreactive and NADPH diaphorase positive, non-neuronal and neuronal
      cell bodies, fibers and putative nerve terminals were identified throughout the
      brain. Even so, the staining was not identical in all regions. NO, synthesized by
      NOS-like enzymes, may play an important role in a diversity of cellular
      mechanisms in the brain of the salmon, including in neural systems related to
      olfactory, visual, hypophysiotrophic, viscero-sensoric and motor functions.

PMID- 7521948
TI  - Nitric oxide synthase in cerebrovascular endothelial cells is inhibited by
      brefeldin A.
AB  - Nitric oxide synthase (NOS) is present within cerebrovascular endothelial cells
      in a distinct membrane-bound juxtanuclear location. The enzyme product, nitric
      oxide, causes vasodilation as well as stimulation of ADP-ribosylations of some
      proteins. The activity of specific stimulatory ADP-ribosylation factors,
      associated with the Golgi complex (GC), has been shown to be blocked by brefeldin
      A (BFA). We present evidence that BFA disperses the GC, disrupts NOS/NADPH
      diaphorase staining and inhibits NOS activity in addition to its previously
      described activities.

PMID- 7521949
TI  - Different susceptibility to neurokinin 1 receptor antagonists of substance P and
      septide-induced interleukin-6 release from U373 MG human astrocytoma cell line.
AB  - In a human astrocytoma cell line U373 MG, the activation of the neurokinin 1
      (NK1) receptor by substance P (SP) increase, in a concentration-related manner (1
      nM to 10 microM), the basal release of interleukin-6 (IL-6) as assayed by an
      ELISA method, in cell supernatants after 18 h of incubation. Septide, a selective
      NK1 receptor agonist, is equipotent to SP in inducing the IL-6 release showing
      similar Emax (2644 +/- 285 and 2830 +/- 271 pg/ml) and EC50 (15.6 +/- 3.6 and
      13.8 +/- 3.2 nM). However, in binding assays on intact cells, septide was an
      about 50-fold weaker displacer of the binding of [3H][Sar9,Met(O2)11]SP than SP
      (Ki's were 0.28 +/- 0.1 nM and 14.2 +/- 5.0 nM for SP and septide, respectively).
      NK2- and NK3-selective agonists (up to 1 microM) had no binding or functional
      effect. Highly selective non-peptide (CP96,345) or peptide (GR82,334) NK1
      receptor antagonists were more effective in antagonizing septide-(IC50's 0.2 +/-
      0.06 nM and 70 +/- 18 nM) than SP-(IC50's 6.7 +/- 1.3 nM and 1.95 +/- 0.4 microM)
      induced IL-6 secretion. These data support the existence, also in human U373 MG
      cells, of a septide-sensitive NK1 receptor subtype(s) and/or epitope(s) blocked
      with high affinity by NK1 antagonist.

PMID- 7521952
TI  - Stimulation of gastric somatostatin mRNA abundance by substance P in capsaicin
      treated rats.
AB  - The spinal afferent neurons serving the stomach influence a variety of different
      gastric functions that together can be considered protective; it is not known
      whether the stomach can adapt to the loss of these neurons. We now report that in
      conscious rats pretreated with capsaicin to lesion small-diameter afferents, but
      not in control rats, i.v. infusion of substance P for 6 h increased the abundance
      of mRNA encoding somatostatin in antrum; there was no change in a reference mRNA,
      glyceraldehyde phosphate dehydrogenase. Substance P had no effect on somatostatin
      mRNA in the gastric corpus in either control or capsaicin-treated rats. An
      increased sensitivity of antral somatostatin cells to substance P may be one of
      the adaptive changes that occurs in the stomach of capsaicin-treated rats.

PMID- 7521950
TI  - The distribution and origin of axon terminals with NADPH diaphorase activity in
      the nucleus of the solitary tract of the rat.
AB  - The distribution and origin of axon terminals containing nitric oxide synthase
      (NOS) were examined in the nucleus of the solitary tract (NST) of the rat by
      NADPH diaphorase histochemistry combined with nodose ganglionectomy. Axon
      terminals with NADPH diaphorase activity were densely distributed in the middle
      and caudal part of the NST. After removal of the nodose ganglion (NG), most of
      the axon terminals with NADPH activity in the NST were eliminated on the
      ipsilateral side. These results indicated that most of the axon terminals with
      NADPH diaphorase in the NST derive from the primary afferent neurons in the NG,
      and that NOS may be richly contained in the central terminals of NG neurons to
      produce nitric oxide as a transmitter.

PMID- 7521951
TI  - Diffusion coefficients and half-lives of nitric oxide and N-nitroso-L-arginine in
      rat cortex.
AB  - In vivo voltammetry was performed in rat brain cortex and in rat brain
      endothelial constitutive NO-synthase preparations. The use of a recent
      microcaptor detecting N-hydroxy- and N-nitroso-L-arginine permitted to find only
      the latest in biological preparations. The construction of a new membrane
      selective electrode for nitric oxide (NO) allowed to assert its absence in these
      preparations at micromolar level. Half-live of N-nitroso-L-arginine was 4 s in
      rat brain cortex and the washout curve of NO after over brain insufflation gave
      an half-life of 10.5 min; their diffusion coefficients in brain were 3.810(-5)
      for NO and 3.910(-6) cm2.s-1 for N-nitroso-L-arginine. These facts indicate that
      N-nitroso-L-arginine is degraded directly into nitrites and citrulline after its
      synthesis by endothelial NO-synthase.

PMID- 7521953
TI  - Chondroitin sulfate proteoglycans protect cultured rat's cortical and hippocampal
      neurons from delayed cell death induced by excitatory amino acids.
AB  - Protective effects of chondroitin sulfate proteoglycans (CSPGs) from rat's brain
      against delayed cell death induced by excitatory amino acids were examined in
      cultured neurons of the rat. CSPGs reduced delayed neuronal death induced by 10
      min exposure to glutamate at a concentration between 100 microM and 1 mM when
      lactate dehydrogenase activity of culture medium was assayed 24 h after the
      exposure. CSPGs also protected neuronal death induced by 200 microM N-methyl-D
      aspartate (NMDA), kainate or 100 microM alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA). CSPGs reduced death of cortical and hippocampal neurons
      even when they were administered at 2 h, but not 6 and 12 h, after the exposure
      to glutamate. These results indicate that CSPGs may have a neuroprotective action
      against acute noxious conditions in the brain.

PMID- 7521954
TI  - Evaluation of distraction osteogenesis by scanning electron microscopy.
AB  - A model of bifocal distraction osteogenesis in the canine model was used to
      assess and quantitate the mineral content of the newly forming bone within the
      canine mandible. A 2-cm defect was created in the body of the mandible, and after
      a posterior osteotomy, the transport disk was advanced at 0.25 mm per 8 hours for
      21 days and then held in rigid fixation for an additional week. As a control for
      this study, three additional dogs underwent the same procedure with the exception
      that the transport disk was not advanced. Electron dispersive spectroscopy
      analysis was performed on the newly formed regenerate bone and compared with
      areas of existing cortical bone of both the transport disk and the mandible. In
      the control model, special note was made of the pericortical callus at the
      osteotomy site as well as of the regenerative bone that filled the 2-cm defect in
      the body of the mandible. Calcium/phosphorous ratios were used to assess the
      composition of the mineralized regions of the mandible. The regenerate bone that
      filled the defect and the mineralized callus surrounding the site of osteoclasis
      in the control mandible were significantly different in composition when compared
      with the regenerate bone that formed during distraction osteogenesis. This
      suggests that distraction osteogenesis may effect an initial matrix production
      that is more similar in composition to the mature cortical bone from which it was
      derived than does periosteal regeneration and filling of an osseous defect.

PMID- 7521955
TI  - Observations on the response of the nasal mucosa to allergens.
AB  - Allergic rhinitis is the sixth most prevalent chronic health condition in the
      United States. To study the pathogenesis of the allergic response, we have used a
      model of nasal provocation with antigen. During the initial reaction of an
      allergic subject to allergen provocation, increases occur in the levels of
      histamine, tryptase, and prostaglandin D2. This pattern of mediator release,
      combined with histologic evidence of mast-cell degranulation, strongly supports
      the role of the mast cell in the acute allergic reaction. The response to
      antigen, however, does not end with mast-cell degranulation. Hours after
      challenge we observed the spontaneous recurrence of symptoms and increased
      responsiveness to antigenic and nonantigenic stimuli. Our central hypothesis is
      that cellular infiltration and activation after antigen challenge are responsible
      for the observed increase in nasal reactivity. The predominant cells in nasal
      lavage 24 hours after challenge are eosinophils and neutrophils, whereas the
      predominant cell in the mucosa is the CD4+ lymphocyte. An early step in the
      movement of cells from the peripheral blood involves adhesion between circulating
      leukocytes and the endothelium. Evidence suggests that vascular endothelial
      adhesion molecule may be responsible in part for the selective adherence of
      eosinophils to the endothelium.

PMID- 7521957
TI  - Remembered and perceived size as a function of familiarity.
AB  - Subjects (42 girls 17 or 18 years old) overlearned to different criteria the
      associations between circles and the symbolic codes that stood for the circles
      when their areas were assessed from memory. Consistent with the prediction from
      the uncertainty theory but conflicting with the prediction from the reperception
      hypothesis, familiarity with the referent stimuli affected the memory-based
      magnitude judgments. Surprisingly, familiarity also affected perceptual judgments
      given to the referent circle stimuli. The possibility of discrete, linguistic
      influences on both perceptual and memory-based processing of sensory reactions is
      discussed.

PMID- 7521956
TI  - Comparative analysis of full-length antigen II/3 from Echinococcus multilocularis
      and E. granulosus.
AB  - The recombinant Echinococcus multilocularis antigen II/3-10 is one of the most
      promising tools for immunodiagnosis of alveolar echinococcosis in human patients.
      Its nucleic acid sequence represents a part of the E. multilocularis gene
      encoding the metacestode antigen II/3, the former being basically present and
      expressed in both E. multilocularis and E. granulosus. Most (94%) patients with
      alveolar echinococcosis respond to infection with a marked anti-II/3-10 IgG
      synthesis; in contrast, most of the cystic echinococcosis patients do not, for
      some reason, recognize the recombinant antigen. We tackled this problem by
      generating cDNA derived from both E. granulosus and E. multilocularis full length
      II/3 genes, performed by reverse transcription and PCR amplification. Sequence
      analysis revealed a very high degree of conservation of the primary sequence of
      the antigen II/3 in both Echinococcus species. cDNA fragments were subcloned and
      expressed in E. coli as fusion proteins with Schistosoma japonicum glutathione S
      transferase. Recombinant proteins were affinity purified and comparatively
      assessed by ELISA with respect to antibody-binding characteristics. Sera from
      patients suffering from cystic echinococcosis showed no significant differences
      in reactivity with the antigens derived from either E. multilocularis or E.
      granulosus. Therefore, parameters other than some minor differences in the
      primary sequence seem to be responsible for the lack of antigen II/3 recognition
      in cystic echinococcosis.

PMID- 7521958
TI  - Test pest.

PMID- 7521959
TI  - [Use of filgrastim (RHU G-CSF) in supplemental treatment of non Hodgkin's
      lymphoma (NHL) in children].
AB  - Clinical application of glycoproteins stimulating the growth (G-CSF),
      differentiation and activity of the cells of granulocyte line has become a
      landmark in the treatment of patients with neutropenia. It has been proved that
      filgrastim (rHU G-CSF) applied after intensive chemotherapy shortens the duration
      of neutropenia and decreases the frequency of occurrence of infections. The paper
      discusses the efficiency and tolerance of filgrastim in children treated for NHL.
      Filgrastim was applied in children with NHL T cell and B cell treated according
      to BFM 86 protocols. It was given in a dose of 5 micrograms/kg daily i.v. The
      duration of therapy ranged from 5-20 days. Altogether 47 cycles were performed.
      25 cycles were performed in 12 children during granulocytopenia (< 1 x 10(9)/l).
      The median time of neutropenia recovery, the frequency of severe infection and
      chemotherapy retardation were significantly lower in the examined than in the
      control group (p < 0.05). In 6 children 22 courses of filgrastim were given
      prophylactically after the cycles of intensive chemotherapy of NHL. Only during
      two courses due to neutropenia the chemotherapy retardation was necessary.
      Toleration of filgrastim was good. Application of filgrastim right after the
      intensive chemotherapy in children with NHL has considerably improved persistent
      realization of treatment programmes. Tolerance of the drug was good.

PMID- 7521960
TI  - Comparative analysis of epidermal growth factor receptor gene expression and
      protein product in benign, premalignant, and malignant prostate tissue.
AB  - In order to more clearly define the status of epidermal growth factor receptor
      (EGFR) in prostate cancer, expression of EGFR transcript and protein was analyzed
      in paired samples of benign and malignant tissues from 30 radical prostatectomy
      specimens. Prostate tumors and high grade prostatic intraepithelial neoplasias
      (PINs) expressed significantly less EGFR protein than benign tissues or low grade
      PINs (P < 0.001). Expression of EGFR mRNA was analyzed in a subset of the same
      samples, and was higher in more prostate tumors than benign specimens (P < 0.05).
      However, differences in mean mRNA expression between malignant and benign tissues
      were not significant. EGFR mRNA was expressed at moderate or low levels in
      equivalent numbers of PIN lesions. These results suggest that, although EGFR mRNA
      expression is somewhat elevated in prostate tumors, EGFR protein expression may
      be down-regulated in the same malignant tissues. Furthermore, our data
      demonstrate phenotypic similarity between prostate tumors and high grade PIN at
      the level of EGFR protein expression.

PMID- 7521963
TI  - Maternal serum inhibin levels in second-trimester Down's syndrome pregnancies.
AB  - Maternal serum inhibin levels were measured in 19 second-trimester pregnancies
      affected by fetal Down's syndrome and 95 unaffected control pregnancies matched
      for gestational age. A statistically significant elevation was found in the
      affected pregnancies compared with the controls (Wilcoxon rank sum test: one-tail
      P = 0.02). The median level in the cases was 1.3 times that in the controls, with
      95 per cent confidence limits of 0.9-1.9. Although the inhibin levels were
      unrelated to those of alpha-fetoprotein and unconjugated oestriol in the same
      samples, there was a statistically significant correlation with human chorionic
      gonadotropin. This together with the relatively small elevation in cases suggests
      that inhibin would be of limited value in maternal screening for Down's syndrome.

PMID- 7521962
TI  - Transforming growth factor beta 1 expression in benign and malignant prostatic
      tumors.
AB  - The expression of transforming growth factor beta 1 (TGF-beta 1) in prostate
      specimens obtained from patients with benign prostatic hyperplasia (BPH, n = 32)
      and prostate carcinoma (n = 66) was investigated using Northern blot analysis and
      immunohistochemistry. Northern blot analysis revealed TGF-beta 1 message (2.5 kb)
      in virtually all of the samples examined, reflecting the ubiquitous nature of
      this growth factor. No statistical difference was found between the levels of
      mRNA detected in benign and malignant tissues due, in part, to the inherent
      heterogeneity of prostate tissue. Immunohistochemical methods using an antibody
      to native TGF-beta 1 revealed a novel pattern of immunoreactivity. Staining
      observed only in certain epithelial cells of benign glands was associated with
      areas of infection rather than tumorigenesis. Interestingly, intense staining was
      also seen in polymorphonuclear leukocytes. No correlation was found with the mRNA
      results, suggesting that this antibody is binding to TGF-beta 1 activated in
      response to infection rather than detecting sites of synthesis of latent TGF-beta
      1.

PMID- 7521964
TI  - Second-trimester maternal serum screening using alpha-fetoprotein, human
      chorionic gonadotrophin, and unconjugated oestriol: experience of a regional
      programme.
AB  - Over a 2-year period from January 1991 to December 1992, second-trimester
      maternal serum screening for Down's syndrome using alpha-fetoprotein (alpha FP),
      human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) was made
      available to five health districts in East Anglia, with a total population of 1.2
      million. Amniocentesis was offered when the risk of Down's syndrome at term was
      1:200 or greater. 25,359 singleton pregnancies were screened, representing an
      uptake of 77 per cent. The recall rate for the 24 per cent of women who had not
      had a dating scan prior to the test was 9.4 per cent compared with 3.9 per cent
      for those who had been scanned (P < 0.0005). Seventy-five per cent (36/48) of
      Down's syndrome pregnancies were detected for a false-positive rate of 4.0 per
      cent. Twenty-five out of 36 of detected Down's syndrome pregnancies were dated by
      scan prior to sampling, and in the 11 remaining cases, the dates were confirmed
      by scan after a high-risk result was obtained. The exclusion of uE3 from the
      screening protocol would have reduced the detection rate to 52 per cent (25/48)
      for the same false-positive rate. Eighty-five per cent of women identified at
      high risk accepted the offer of an amniocentesis. Other fetal abnormalities
      detected were trisomy 18 (3), trisomy 13 (2), 45,X (6), 69,XXX (5), other
      chromosome abnormalities (9), open neural tube defects (26), hydrocephalus (7),
      abdominal wall defects (4), and steroid sulphatase deficiency (6).

PMID- 7521961
TI  - In vivo and in vitro effects of androgen on fibroblast growth factor-2
      concentrations in the human prostate.
AB  - Prostatic growth is primarily regulated by dihydrotestosterone (DHT). Recent
      studies have demonstrated that a large number of growth factors are present in
      the human benign prostatic hyperplasia (BPH) prostate, including epidermal growth
      factor (EGF), transforming growth factor-alpha (TGF-alpha), transforming growth
      factor beta (TGF-beta), insulin-like growth factor (IGF), and basic fibroblast
      growth factor (bFGF) (FGF-2). DHT may mediate its mitogenic effects in the
      prostate by regulating growth factors. To test this hypothesis, we have utilized
      a histoculture androgen sensitivity assay (HASA) in which 3H-thymidine
      incorporation is measured in aliquots of BPH tissue in histoculture with either
      added DHT or hydroxyflutamide (HF). The resulting DHT/HF ratio is an expression
      of the androgen sensitivity of the tissue. In this study, we have compared the
      DHT/HF ratio for 3H-thymidine incorporation to the DHT/HF ratio for FGF-2
      measured in the histocultured prostates. The DHT/HF ratio for the HASA studies of
      3H-thymidine incorporation averaged 2.68 compared to the DHT/HF ratio for FGF-2
      in the same specimens of 1.01. These values were significantly different,
      therefore indicating no relationship between DHT stimulation and FGF-2 levels. In
      addition, FGF-2 levels were measured in human BPH prostates from patients
      medically castrated with megesterol acetate and estradiol 17-beta prior to
      surgery. These values were not significantly different, and therefore do not
      suggest any effect of DHT on the concentration of prostatic FGF-2. Although these
      studies did not show any effect of DHT on the regulation of prostatic FGF-2, they
      do indicate that the HASA assay is feasible and appropriate to use in the study
      of relationships between DHT and various growth factors.

PMID- 7521965
TI  - Maternal serum screening and triploidy.

PMID- 7521966
TI  - The Leeuwenhoek Lecture, 1993. Peptide vaccines: dream or reality?
AB  - Small fragments of micro-organisms which elicit protective immune responses have
      now been identified for several disease-causing agents. This major advance has
      made it possible to envisage the chemical synthesis of vaccines which could
      replace those in current use and may also furnish products which cannot be made
      by traditional methods. In my lecture I will illustrate the principles involved
      by describing the advances made with synthetic vaccines for foot-and-mouth
      disease, hepatitis B and malaria.

PMID- 7521967
TI  - Use of a nonradioactive genetic probe identified, synthesized, and labeled in the
      polymerase chain reaction.
AB  - This study introduces a strategy to identify and produce sequences useful as
      genetic markers, or native genetic probes for DNA-DNA hybridization in bacterial
      strains where the genetics is not well described. Actinobacillus actinomy
      cetemcomitans (A.a.) was used as an example. Fifty ng genomic DNA from A.a. ATCC
      33384 and Haemophilus aphrophilus ATCC 33389 was amplified in a thermocycler
      using a single 10-mer primer. The PCR products were separated by electrophoresis
      on a 1% submarine agarose gel containing ethidium bromide and visualized by UV
      illumination, and the strain-specific amplitypes were compared. DNA from two
      bands, 0.9 and 4 kb, unique for the A.a. strain, was cut out, amplified under
      high stringency with the same primer and labeled by replacing 33.3 microM dTTP
      with digoxigenin-labeled dUTP in the reaction mixture. The labeled probe was then
      repeatedly used for hybridization to DNA from various A.a., H. aphrophilus, and
      other bacterial strains of the Pasteurellaceae family. The results showed that
      the 0.9-kb probe detected all A.a. tested, and distinguished it from other
      closely related bacterial species. We conclude that the described strategy is
      useful for identifying and selecting genetic sequences useful as genetic markers
      in A.a.

PMID- 7521968
TI  - Oxyfuel in Alaska: use of interleukins to monitor effects on the immune system.
AB  - During a 4-week period in late November and early December 1992, blood samples
      from individuals exposed to auto emissions derived from oxyfuel were analyzed.
      Effects on the immune system were measured by monitoring plasma interleukin 6 (IL
      6) levels in a total of 22 subjects at the beginning and the end of the workday.
      After approximately 8 h of workplace exposure, mean levels of IL-6 of 2.5 pg/ml
      were obtained. While some subjects showed increasing levels at the end of the
      workday, there was no difference between morning and evening IL-6 means. Our
      conclusion is that single day exposures to oxyfuel and its combustion products
      does not show an immediate effect on the immune system as judged by serum IL-6
      levels.

PMID- 7521969
TI  - Chromosome ends catch fire.

PMID- 7521972
TI  - [Effect of serum glucose on the function of pancreatic exocrine in diabetic
      rats].
AB  - In streptozotocin induced diabetic rats, the amylase content and amylase release
      from isolated pancreatic acini stimulated by CCK-8 were significantly decreased.
      Both decrease could be reversed when vanadate, a chemical which is capable of
      lowering blood glucose without effect on serum insulin level in diabetic rats,
      was given intragastrically. The in vitro analysis showed that high concentration
      of glucose could inhibit 3H-leucine incorporation in pancreatic acini and
      increase the MDA content in pancreatic acinar membrane. These results indicated
      that hyperglycemia might be one of the reasons which cause the dysfunction of
      pancreatic exocrine in diabetic rats.

PMID- 7521973
TI  - The application of educational technology to occupational safety and health
      training.
AB  - For years, lectures and films have formed the basis of health and safety
      training. New communication systems, however, allow trainees such luxuries as
      receiving instruction from a source that might be hundreds of miles away. Various
      multimedia systems are described, including CD-ROM, virtual reality, and others
      that may some day become the mainstays of worker training.

PMID- 7521971
TI  - [Inhibition of gastric myoelectric activity and gastric motility induced by
      microinjection of substance P into caudate nucleus in mouse].
AB  - Changes of gastric myoelectric fast wave, slow wave and gastric motility were
      studied after microinjection of substance P or ACh into caudate nucleus in an
      attempt to find the interaction between the two substances. Gastric myoelectric
      activity and motility were recorded by a RM-6200 four channel recorder and then
      delivered to a IBM-PC computer for analysis. After microinjection of SP or ACh
      into caudate nucleus, the gastric myoelectric fast wave and gastric motility were
      significantly suppressed, while the slow wave was not significantly changed.

PMID- 7521970
TI  - [Effect and its mechanism of substance P on contractile activity of isolated
      antral muscle strips of rat].
AB  - The present study was aimed at investigating the effect of substance P (SP) on
      the contractile activity of isolated antral muscle strips of rat and its
      underlying mechanism. Isolated strips were incubated in an organ bath into which
      SP was added with or without pretreatment of some antagonists or inhibitors. The
      results were as follows: (1) SP increased the contractile amplitude of the strips
      in a dose-dependent manner from 8 x 10(-11) to 8 x 10(-7) mol. At 4 x 10(-8) mol
      the amplitude was increased by 160.9 +/- 23.0%, while the automaticity of the
      strips was not affected. (2) This effect of SP could be partially inhibited by
      hexamethonium (ganglionic blocker), cyproheptadine (blocker of 5-HT2 receptor),
      diphenhydramine (blocker of H1 receptor), or aminophylline (inhibitor of
      phosphodiesterase), but not by atropine, propranolol, phentolamine, haloperidol,
      or naloxone. These results suggested that SP might be a non-cholinergic
      excitatory transmitter. Its spasmogenic action might be mediated by activating 5
      HT neurons, which elicited release of histamine or directly acted on muscle
      cells.

PMID- 7521975
TI  - Aprotinin in therapeutic doses inhibits chromogenic peptide substrate assays for
      protein C.

PMID- 7521974
TI  - A method for the quantitation of protamine in plasma.
AB  - A unique and simple colorimetric method for the quantitation of plasma protamine
      levels has been developed. The method is established on the competitive binding
      displacement mechanism between protamine and heparin-azure A dye complex, and the
      metachromatic color change of azure A dye in the presence of heparin. Because the
      method is based on the clinical specificity of protamine as the heparin
      antagonist, it is specific for protamine quantitation. Plasma protamine levels
      determined by this method are within 94% of accuracy when compared with their
      aqueous counterparts determined by the conventional Lowry protein assay. Since
      the method measures the protamine excess after heparin neutralization, it
      potentially could be employed during clinical heparin reversal with protamine to
      monitor protamine excess. In addition, the method may provide a useful means to
      identify the mechanism of the so-called "heparin rebound".

PMID- 7521976
TI  - HLA-B15: a widespread and diverse family of HLA-B alleles.
AB  - HLA-B15 embraces a multiplicity of antigenic specificities which vary in their
      distribution amongst human populations. To correlate B15 molecular structure with
      the serological picture we have sequenced alleles encoding the various
      subspecificities of the B15 antigen: B62, B63, B75, B76 and B77, and a number of
      "variants" of these antigens including the 8w66 split of B63. HLA-B63 (B*1517)
      and 8w66 (B*1516) heavy chains have sequence identity to B17 in the alpha 1 helix
      correlating with the antigenic crossreactivity of these molecules. HLA
      B77(B*1513) and B75 (B*1502) heavy chains differ solely in segments determining
      the Bw4 and Bw6 public epitopes, consistent with the serological description of
      the B77 and B75 antigens. One allele encoding the B76 antigen (B*1512) appears to
      be the product of gene conversion between the HLA-A and -B loci and differs from
      B*1501 in codons 166 and 167. In contrast, a second allele encoding the B76
      antigen (B*1514) differs from B*1501 by an unrelated substitution in codon 167
      which confers similarily with B45, an antigen crossreactive with B76. A third
      allele encoding B76, B*1519, differs from B*1512 by a unique point substitution
      in exon 4. Three alleles encoding variant B15 and B62 antigens (B*1508, B*1511
      and B*1515) differ from B*1501 by localized clusters of substitutions that
      probably result from interallelic conversion. The B15 sequences described in this
      paper, in combination with those previously determined, define a family of 22
      alleles, including those encoding the B46 and B70 antigens. Within this family
      the patterns of allelic substitution are analogous to those of other HLA-A and -B
      families, in that pairwise differences almost always involve functional positions
      of the antigen recognition site and recombination is the major agent of
      diversification.

PMID- 7521977
TI  - Brain and liver lipid peroxidation levels following acute and short-term lindane
      administration in the rat.
AB  - Oxidative stress-related parameters in rat brain and liver were evaluated
      following acute (60 mg/kg i.p., 2 and 24 h after dosing) or short-term (1000 ppm
      in the diet for 90 days) lindane administration. Both treatments elicited a
      significant accumulation of lindane in brain and liver, with convulsions observed
      in short-term and 24-h lindane-treated rats. In these conditions, lindane
      exposure did not alter brain lipid peroxidation, assessed as thiobarbituric acid
      reactants formation and spontaneous chemiluminescence, parameters that were
      enhanced in the liver. The activities of antioxidant enzymes in the brain
      (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase
      and glucose 6-phosphate dehydrogenase) were not modified by acute lindane
      treatment, while brain glutathione content was significantly reduced by 13%. It
      is concluded that lindane does not alter the oxidative stress status of the brain
      as occurs in liver, regardless of the time of exposure of rats to either acute or
      short-term administration of the insecticide.

PMID- 7521978
TI  - Comparison of different assays for the quantitation of FK 506 levels in blood or
      plasma.
AB  - In a prospective study, we evaluated the analytical performance of different
      assays for the quantitation of FK 506 in blood and plasma. The new whole blood
      IMX assay was compared with four modifications (liquid/liquid or solid/liquid
      extraction of blood or plasma respectively) of the standard enzyme-linked
      immunosorbent assay (ELISA). Both assays utilize the same monoclonal antibody for
      detection of FK 506. Using isolated FK 506 metabolites generated in vitro, this
      antibody was shown to recognize not only the unmodified parent drug but also FK
      506 metabolites. In stable liver-grafted patients, sensitivity of both
      modifications of the whole blood ELISA was adequate. In contrast, in some stable
      patients, plasma ELISA was not able to detect FK 506; this was observed mainly
      after liquid/liquid extraction of FK 506. Sensitivity of the IMX assay was also
      low; in six of 10 stable liver-grafted patients, IMX levels were below the limit
      of detection. In all assays, FK 506 levels were found to be elevated during
      episodes of liver dysfunction; a possible explanation for this effect would be
      that of accumulation of cross-reacting FK 506 metabolites. As FK 506 metabolites
      are known to be less immunosuppressive than the parent drug, liver function
      should always be taken into account if IMX or ELISA levels are used for drug
      monitoring.

PMID- 7521979
TI  - Multicenter comparison of tacrolimus (FK 506) whole blood concentrations as
      measured by the Abbott IMX analyzer and enzyme immunoassay with methylene
      chloride extraction.
AB  - A multicenter comparison was made between the Abbott IMX and enzyme-linked
      immunosorbent assay (ELISA) procedures for analysis of tacrolimus (FK 506) in
      whole blood. Proficiency samples and 853 patient specimens obtained after various
      organ transplantations were assayed by 13 laboratories. Both groups of test
      samples yielded slightly lower (7 and 13%) values by the IMX method, but the
      difference is not clinically meaningful. The type of organ transplant was not a
      factor that contributed to assay variation. The Abbott IMX results were
      essentially equivalent to ELISA and considerably facilitates monitoring of FK 506
      therapy.

PMID- 7521980
TI  - Comparison of three immunoassays for the determination of N-acetylprocainamide.
      Determination of false elevations by a polyclonal antibody-based method.
AB  - The performance of the ROCHE FP NAPA reagent, a newly reformulated monoclonal
      antibody-based fluorescence polarization immunoassay (FPIA) for N
      acetylprocainamide, was compared with two commercially available polyclonal
      antibody-based immunoassays, the Abbott TDx and Syva EMIT. Although excellent
      correlation was observed between the ROCHE FP NAPA reagent and the Syva EMIT
      reagent, a positive bias was observed in the correlation between the ROCHE FP
      NAPA reagent and the Abbott TDx reagent. The bias in the TDx method was
      investigated further by the concurrent high-performance liquid chromatography
      (HPLC) analysis of patient samples. Insignificant differences (p < 0.05) were
      observed between the HPLC and ROCHE FP values. The TDx system, however, yielded
      significantly higher (p < 0.0005) results than did HPLC.

PMID- 7521982
TI  - Assessing AIDS/HIV prevention: what do we know in Europe? General population.
AB  - One aim of this EC Concerted Action Programme has been to compare and contrast
      AIDS/HIV prevention strategies aimed at the general population, and the methods
      used to assess them, in order to arrive at a better understanding of how public
      education in this area might optimally be effected and evaluated. To this end,
      data have been collected on interventions and their evaluation for selected
      European countries by means of site visits, postal questionnaires and expert
      meetings of those involved. These data have been analysed where possible in
      relation to other relevant variables including the social and political context
      in which AIDS public education has taken place, the existing tradition of health
      education, the financial and manpower resources available and the nature of the
      HIV epidemic in each country. Initial analysis shows that there have been
      remarkable parallels between AIDS public education campaigns in different
      European countries in terms, for example, of their sequence and progression, and
      their content. At the same time, essential differences are apparent with respect
      to the ease with which it has been possible to implement strategies, the tone and
      style of initiatives, and their reception by and effect on the general
      population. Attempts to attribute these differences to specific cultural,
      political or operational factors are difficult, but the cross national comparison
      holds valuable lessons for both campaigns and their evaluation.

PMID- 7521981
TI  - [The complex assessment of myocardial electrical instability in exacerbated
      ischemic heart disease].
AB  - Risk of sudden coronary death in patients with unstable stenocardia is studied
      insufficiently. 39 patients with unstable stenocardia underwent Holter's
      monitoring, loading tests and invasive programmed ventricular stimulation coming
      lately into increasingly wide use for assessment of myocardial electric
      stability. Programmed stimulation allowed to single out two groups of patients:
      with ventricular tachycardia (56.4%) and without it (43.6%). Results obtained by
      aforementioned methods showed no correlation which is explained by the authors as
      being due to different pathogenetical mechanisms initiating ventricular
      arrhythmias. Thus, for example, rhythm disorders emerged not infrequently in the
      periods of ischemia during Holter's monitoring while myocardial ischemia was not
      observed in all cases of programmed ventricular stimulation. That is why complex
      approach needs to be pursued for assessment of electric stability of myocardium
      in patients with advancing stenocardia.

PMID- 7521983
TI  - [Comparison of acid and pepsinogen secretion control by oxyntopeptic cell of
      amphibians].
AB  - Pepsinogen and HCl secretion in the amphibian stomach is performed by a single
      cell type, the oxyntopeptic cell. The distribution of pepsinogen in gastric
      mucosa of Bufo marinus is heterogeneous and higher concentrations are located in
      the fundus. Both secretions respond to the same secretagogues. Histamine induces
      the highest response for the two secretions. Carbachol alone, without the
      endogenous histamine component, has a small effect. Forskolin and 8Br-cAMP have a
      similar effect to histamine. The Ca2+ ionophore, A23187, and the diacylglycerol
      analogue, octanoylacylglycerol (OAG) have a small effect on both secretions as
      carbachol. Joint addition of histamine and carbachol, or forskolin and carbachol,
      or of OAG and 8Br-cAMP induce a potentiated response for the two secretions.
      Quantitative analysis of responses and study of the relationship between them
      during stimulation with histamine plus carbachol revealed a non parallel and
      uncoupled pattern of stimulation for acid and pepsinogen secretions.

PMID- 7521984
TI  - [Clinical study of intraurethral stent for patients with benign prostatic
      hypertrophy with 1-year follow up].
AB  - Seven consecutive patients with acute retention due to benign prostatic
      hyperplasia, were treated by insertion of an intraurethral stent using endoscopy
      under mucosal anesthesia. The patients were between 68 and 86 years old with an
      average age of 79.7 years. During the 1-year follow-up period all patients had
      satisfactory voiding. No complication or renal dysfunction were found. This
      device is a good alternative to an indwelling catheter in patients awaiting
      prostatic surgery and also in those who are either unfit or unwilling to undergo
      prostatectomy.

PMID- 7521985
TI  - [A case of prostatic cystadenoma].
AB  - We report a case of prostatic cystadenoma in a 45-year-old man with the complaint
      of urinary retention. The large mass was palpated on rectal examination. The
      tumor was localized in the position of the left lobe of the prostate and was seen
      as multi-ocular on computerized tomographic (CT) scan. The serum levels of
      prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) were
      slightly elevated. The tumor was enucleated retropubically, it weighed 210 g and
      had an multilocular structure macroscopically. The cyst seen on microscopic
      examination was lined with cuboidal or columnar epithelial cells and the lining
      cells were focally multilayered and formed papillary projections. The stroma
      surrounding the glands was composed of fibrous tissue containing smooth muscle
      fibers. The epithelial cells were immunoreactive for PAP and PSA.

PMID- 7521988
TI  - Presence of extrapyramidal side-effects from droperidol in low dose.

PMID- 7521987
TI  - Biomicroscopic and histopathologic considerations regarding the feasibility of
      surgical excision of subfoveal neovascular membranes.
AB  - Surgical excision of subfoveal neovascular membranes may result in recovery of
      excellent visual acuity in patients with presumed ocular histoplasmosis but not
      in patients with age-related macular degeneration. To provide an explanation for
      this discrepancy, I analyzed the clinical and histopathologic findings in five
      patients with presumed ocular histoplasmosis. These findings provide evidence
      that the new vessels arising in the choroid in these patients usually grow within
      the subsensory retinal space and not in the subpigment epithelial space, as
      occurs in patients with age-related macular degeneration. In presumed ocular
      histoplasmosis, the new vessels are partly engulfed by a monolayer of
      proliferating retinal pigment epithelium. Surgical excision of this membrane
      permits reapproximation of the retinal receptors and native pigment epithelium
      and may be associated with remarkable return of visual acuity.

PMID- 7521986
TI  - Electron microscopic and immunochemical studies in a patient with hepatitis C
      virus infection and mixed cryoglobulinemia type II.
AB  - The authors describe patient with hepatitis C virus (HCV) infection and mixed
      cryoglobulinemia type II in whom multiorgan failure was associated with deposits
      of typical, electron-microscopically visualized paracrystalline tubules in the
      organs studied. The patient's plasma cryoprecipitate was comprised of monoclonal
      IgM rheumatoid factor, polyclonal IgG, HCV RNA, and complement component C3. Of
      the polyclonal IgG, almost half was anti-HCV. The molar ratio between IgG and IgM
      was approximately 1.5 to 1. On peripheral blood films the cryoprecipitate formed
      cloudlike structures, which may be a useful diagnostic clue in mixed
      cryoglobulinemia type II. The ultrastructure of plasma cryoprecipitate and of
      deposits in skin, renal glomerular capillaries, and blood monocytes was
      identical. The cross-sectional diameter of the tubules was 30.7 +/- 1.6 nm (mean
      +/- 1 SD), and they appeared to be surrounded by eight electron-lucent dots.
      Deposition in organs of complexes containing HCV antigens and antibodies,
      rheumatoid factor, and C3 contributed to the multiorgan disease in this patient.

PMID- 7521989
TI  - Pattern of ribonucleic acid synthesis in human primary spermatocytes.
AB  - RNA synthesis was studied autoradiographically using [3H]-uridine at different
      stages of human spermatogenesis and especially at the pachytene stage.
      Morphological and functional evidence have shown the X Chromosome to be
      allocyclic relatively to the autosomes, and apparently inactive throughout the
      whole meiosis. No RNA precursor was incorporated by the X at any stage of male
      meiosis. The authors suggest that this technique could be used in cases of human
      rearranged chromosomes, in order to elucidate the mechanism of spermatogenic
      breakdown in cases of hypofertility or sterility in humans.

PMID- 7521991
TI  - Evaluation of nuclear maturity in human spermatozoa obtained by sperm-preparation
      methods.
AB  - Change in the nuclear maturity has been considered as an index of sperm quality.
      This is done by using aniline blue staining that stains spermatozoa with
      disturbances in the chromatin condensation. Therefore, this technique was used to
      evaluate the quality of sperm obtained by sperm preparation methods. In 14 semen
      samples from healthy donors with normal semen analysis and normal forms, the swim
      up (SU), Percoll gradient centrifugation (PG), glass wool column filtration (GW)
      and sedimentation-migration (SM) were performed. GW and SM methods presented the
      lowest number of spermatozoa with alteration in the nuclear maturity (ANM), 11,
      14% and 12, 42% compared to native semen (19%) (P < 0.005 and P < 0.05
      respectively). SU and PG did presented no significant difference compared to
      native semen. In tests using the four methods, approximately 60% of the ANM
      occurred in normal spermatozoa. In the cells with pathologic abnormalities and
      ANM, 74.5% corresponded to macrocephalic forms, as this abnormality correlated
      mainly with ANM. It is concluded that in a semen sample with a higher percentage
      of normal forms, approximately 19% will have an ANM. GW and SM methods obtain the
      lowest percentage of ANM. ANM presents itself in 98% of the macrocephalic forms
      and they are effectively isolated with the PG method. The practice of this simple
      technique may orientate towards the sperm preparation methods to be used in
      assisted reproduction.

PMID- 7521992
TI  - Discontinuing antithyroid drug therapy before ablation with radioiodine in Graves
      disease.
AB  - OBJECTIVE: To determine the relative effects on thyroid hormone levels of
      discontinuing antithyroid drug therapy and subsequent ablation with radioiodine
      in patients with hyperthyroid Graves disease. DESIGN: A clinical trial with a
      prospective analysis of the relative change in thyroid hormone levels over time
      in response to therapy in two study groups. SETTING: An outpatient endocrine
      clinic at a tertiary care hospital. PATIENTS: 21 patients with a clinical
      diagnosis of hyperthyroid Graves disease scheduled to receive ablation therapy
      with radioiodine (131I): 17 patients were pretreated with antithyroid drugs, and
      4 were not. METHODS: Antithyroid drugs were stopped 6 days before radioiodine
      therapy. Patients were monitored clinically and biochemically with measurement of
      free and total levels of thyroxine (T4) and triiodothyronine (T3) on days -6, -3,
      -1; the day of radioiodine therapy; and days 1, 2, 3, 4, 5, 7, and 14. RESULTS:
      Before radioiodine treatment and compared with baseline measurement, the mean
      increase in free T4 levels after discontinuation of antithyroid therapy was 86%
      (95% CI, 16.1% to 156%), with a concurrent mean increase in free T3 levels of
      71.6% (CI, 31% to 112%). Radioiodine therapy resulted in a mean decrease in free
      T3 levels of 28.7% (CI, -44.1% to -13.2%), a mean decrease in total T3 levels of
      22.9% (CI, -39.4% to -6.4%), and stability in free and total T4 levels rather
      than aggravation of thyrotoxicosis. A smaller group of patients not receiving
      antithyroid drugs experienced a course qualitatively similar to that of
      pretreated patients after 131I treatment, with a mean reduction in free T4 levels
      of 39.8% (CI, -69.9% to -9.7%) and a mean decrease in free T3 levels of 49.4%
      (CI, -93.7% to -5.1%). CONCLUSION: Short-term increases in thyroid hormone levels
      in patients with Graves disease receiving radioiodine ablation occur primarily as
      a result of discontinuing antithyroid therapy rather than as a result of
      treatment with 131I. Stability or decrease in thyroid hormone levels, rather than
      further elevation, occurs during the 2-week interval after ablation therapy with
      131I. Antithyroid drug therapy before radioiodine ablation may have little effect
      on the short-term biochemical course after 131I therapy for Graves disease. The
      homogeneity of our sample regarding age, diagnosis, and general health may
      prevent application of these findings to other populations without further study.

PMID- 7521990
TI  - Leukocytospermia in male infertility patients in China.
AB  - Recent studies have revealed a high prevalence of leukocytospermia (> 1 x 10(6)
      white blood cells ml-1 semen) in male infertility patients in the USA and certain
      European countries, and have implicated white blood cells as a cause of
      infertility. Since leukocytospermia may often be attributed to male genital-tract
      infections, its prevalence could vary widely in different populations depending
      on factors such as sexual practices and the prevalence of sexually transmitted
      pathogens. In the study described here the incidence of leukocytospermia was
      determined in a group of 101 male infertility patients and a small reference
      group of normal fertile men in Beijing, China. Seminal white blood cells (WBC)
      and WBC sub-populations were enumerated by peroxidase staining and
      immunohistological assay. Eight out of 101 (7.9%) samples from infertility
      patients and 0/10 samples from fertile donors were leukocytospermic. The
      incidence of leukocytospermia in the Chinese infertility patients was
      considerably lower than the 23% incidence observed in a recent study of
      infertility patients in the USA using a similar technique. All but one of the
      patients with leukocytospermia had a poor sperm count and/or poor sperm motility.
      However, due to the low incidence of leukocytospermia and the small number of
      patients in this group, a statistically significant association between
      leukocytospermia and poor semen quality was not attained. The simple peroxidase
      test correlated well with the more expensive and technically demanding
      immunohistological assay for detection of white blood cells in semen.

PMID- 7521993
TI  - Antithyroid drugs and radioiodine therapy: a grain of (iodized) salt.

PMID- 7521994
TI  - [Indications for palliative surgery in digestive cancerology].
AB  - The data of the literature demonstrate the poor global results of surgical
      treatment of the principal gastrointestinal cancers: oesophagus, stomach, bile
      ducts, liver, exocrine pancreas, colon and rectum. Surgery which was thought to
      be curative all too frequently proves to be simply a palliative procedure. The
      risk of failure is so high that a strategy should now be systematically adopted,
      combining surgery, radiotherapy, chemotherapy and symptomatic treatments. The
      rigor of this multidisciplinary approach is based on comparative studies
      confirming the prospective series and measuring the quality and duration of
      survival. Some protocols provide considerable improvement, for example
      preoperative radiotherapy of cancers of the rectum, or propose an interesting
      alternative such as the combination of radiotherapy and chemotherapy in cancer of
      the oesophagus. The participation of surgeons in multicentre prospective studies
      should validate and improve current oncological practice while also evaluating
      the contribution of a new method such as laparoscopic surgery. This commitment
      includes a definition of therapeutic objectives, definition of the reference
      treatment, selection of the criteria of the quality of the procedures involved in
      this treatment and objective assessment of the results.

PMID- 7521996
TI  - Formation of chlorocatechol meta cleavage products by a pseudomonad during
      metabolism of monochlorobiphenyls.
AB  - Pseudomonas cepacia P166 was able to metabolize all monochlorobiphenyls to the
      respective chlorobenzoates. Although they transiently accumulated, the
      chlorobenzoate degradation intermediates were further metabolized to
      chlorocatechols, which in turn were meta cleaved. 2- and 3-Chlorobiphenyl both
      produced 3-chlorocatechol, which was transformed to an acyl halide upon meta
      cleavage. 3-Chlorocatechol metabolism was toxic to the cells and impeded
      monochlorobiphenyl metabolism. In the case of 2-chlorobiphenyl, toxicity was
      manifested as a diminished growth rate, which nevertheless effected rapid
      substrate utilization. In the case of 3-chlorobiphenyl, which generates 3
      chlorocatechol more rapidly than does 2-chlorobiphenyl, toxicity was manifested
      as a decrease in viable cells during substrate utilization. 4-Chlorobenzoate was
      transformed to 4-chlorocatechol, which was metabolized by a meta cleavage pathway
      leading to dehalogenation. Chloride release from 4-chlorocatechol metabolism,
      however, was slow and did not coincide with rapid 4-chlorocatechol turnover.
      Growth experiments with strain P166 on monochlorobiphenyls illustrated the
      difficulties of working with hydrophobic substrates that generate toxic
      intermediates. Turbidity could not be used to measure the growth of bacteria
      utilizing monochlorobiphenyls because high turbidities were routinely measured
      from cultures with very low viable-cell counts.

PMID- 7521995
TI  - Transposition in Lactobacillus sake and its abolition of lactocin S production by
      insertion of IS1163, a new member of the IS3 family.
AB  - This report presents the nucleotide sequence and insertional activity of IS1163,
      which is a new member of the IS3 family of transposable elements. Analysis of
      spontaneous mutants of the lactocin S-producing Lactobacillus sake strain L45
      show that the bacteriocin-negative phenotype is due to either loss of the
      producer plasmid or the insertion of IS1163 into the lactocin S operon (las
      operon). The data further show that insertional inactivation of the lactocin S
      operon is the result of a transposition event involving a chromosomally located
      donor copy of IS1163. Although the insertions described are clustered within a
      250-bp region of the las operon, there are no features of the insertion sites to
      suggest target-specific insertion of IS1163. The overlapping, frameshifted
      organization of the two major open reading frames found in IS1163 is typical for
      the IS3 family, but the structure of the putative frameshift region includes
      features which distinguish IS1163 from the other members of the group. The
      insertional activity of IS1163 in L. sake L45 has aided in identifying regions of
      pCIM1 essential for lactocin S production and may have further practical
      applications as a mutational tool in L. sake.

PMID- 7521997
TI  - Development of a method for detection of enteroviruses in shellfish by PCR with
      poliovirus as a model.
AB  - The application of the PCR to complex samples is hindered by amplification
      inhibitors. We describe a reverse transcription-PCR-based method capable of
      inhibitor removal for the detection of enteroviruses in shellfish. Initial virus
      extraction stages based on a modified polyethylene glycol precipitation technique
      (G.D. Lewis and T.G. Metcalf, Appl. Environ. Microbiol. 54:1983-1988, 1988) were
      followed by virus purification with 1,1,2-trichloro,2,2,1-trifluoroethane and
      concentration by ultrafiltration. A guanidine isothiocyanate-glass powder
      extraction system was utilized for sample lysis, RNase protection, and nucleic
      acid purification. Removal of PCR inhibitors and method sensitivity were
      quantified in shellfish (oysters and mussels) seeded with poliovirus. PCR sample
      tolerance exceeded 4 g for depurated shellfish; however, polluted field samples
      were more inhibitory. Virus recoveries of 31% for oyster extracts and 17% for
      mussel extracts and nucleic acid extraction reverse transcription-PCR detection
      limits down to 1 PFU yielded an overall sensitivity limit of < 10 PFU of
      poliovirus in up to 5 g of shellfish. PCR-positive results were obtained from a
      variety of polluted field samples naturally contaminated with human
      enteroviruses. The methods developed for virus recovery and PCR inhibitor removal
      should be equally applicable to detection of other RNA viruses such as hepatitis
      A virus, Norwalk virus, and other small round-structured viruses in shellfish.

PMID- 7521999
TI  - [Tumor markers in prostate cancer].
AB  - The present status of tumor markers in prostate cancer, especially prostate
      specific antigen (PSA), for diagnosis and follow-up of prostate cancer patients
      was reviewed. Due to tissue-specific protein of PSA as well as PAP, serum PSA
      levels may increase in patients with benign hyperplasia (BPH) which is the
      disease necessary for differential diagnosis from prostate cancer. Therefore, it
      has been believed to be difficult to differentiate early stages of prostate
      cancer from BPH using only PSA determination. However, with the use of recently
      developed assay systems, the detection of PSA-protease inhibitor complex, or PSA
      density, the detection of early stages of prostate cancer may be possible. In
      following up prostate cancer patients, serially determined PSA is one of the best
      tools to evaluate treatment response and early detection of disease progression.

PMID- 7521998
TI  - [Diagnostic imaging of prostate cancer].
AB  - Cancer nodules in early prostate cancer are mostly visualized as hypoechoic
      lesions on ultrasonogram. In a small number of prostate cancers, the cancer
      nodule is isoechoic and difficult to visualize. In advanced prostate cancer, the
      prostate is enlarged asymmetrically and deformed. The internal echo pattern of
      the prostate with advanced prostate cancer has usually been demonstrated as a
      mixed or mosaic architecture including both hypoechoic and hyperechoic lesions.
      According to several reporters, the sensitivity and specificity of transrectal
      sonography were approximately 80% and 90%, respectively. Doppler color flow
      imaging was applied to transrectal sonography in the present study. The detection
      rate of blood flow image was higher in the cases of prostate cancer than in other
      cases with normal or benign prostatic hyperplasia. The detection rate became
      higher according to the stage of the disease, but no difference was noticed among
      cases with different tumor grades. Blood flow rapidly became lower after
      castration and was undetectable 4 weeks after the treatment. CT scan was not
      useful for the diagnosis of prostate cancer. MRI seemed promising because it can
      visualize the internal architecture and cancer lesion of the prostate.

PMID- 7522000
TI  - [Screening test for prostate cancer].
AB  - Prostate specific antigen (PSA), digital rectal examination (DRE) and transrectal
      ultrasonography (TRUS) are widely used for the detection of prostate cancer. The
      sensitivity and positive predictive value of PSA are most excellent among these
      modalities. However, the sensitivity of PSA was 73% when the cut off value was
      6ng/ml. In the general clinical practice the use of three screening modalities
      must be recommended to improve the detection rate. However, the mass screening
      which has to diagnose many subjects during a short period should be mainly
      conducted by PSA, because blood sampling for PSA was performed with other kind of
      mass screening without any specialists (urologists). We are now investigating the
      effects of age specific PSA and PSA velocity to improve the sensitivity of PSA.
      It is estimated that the prostate cancer death and the prevalence will rapidly
      increase in Japan. Therefore, we had better start the preventative research
      including mass screening. To prove the significance of mass screening program,
      pilot studies in well executed randomized prospective protocols are urgently
      needed.

PMID- 7522001
TI  - [Effective measures against side effects by increasing ACNU dose for malignant
      glioma: effects on digestive organs].
AB  - Loading therapy consisting of the ACNU regimen was instituted as postoperative
      anticancer chemotherapy for malignant gliomas. The efficacy rate of the regimen
      was 25% at a dose of 3 mg/kg. A high incidence of hematological changes, such as
      leukopenia (neutropenia) and thrombocytopenia, were observed after chemotherapy.
      The former could be prevented by the administration of G-CSF, but platelet
      infusions were necessary in some patients for amelioration of thrombocytopenia.
      Gastroenterological symptoms, such as nausea and vomiting, were also frequently
      noted. Granisetron (Kytril), which is a recently developed selective competitive
      inhibitor of the 5-HT3 receptor, was used for the treatment of these adverse
      effects, and was found to be clinically effective.

PMID- 7522003
TI  - Argon green vs krypton red laser photocoagulation for extrafoveal choroidal
      neovascularization. One-year results in ocular histoplasmosis. The Canadian
      Ophthalmology Study Group.
AB  - OBJECTIVE: To determine whether the krypton red laser is superior to the argon
      green laser or vice versa for treatment of choroidal neovascularization located
      between 200 and 2500 microns from the center of the foveal avascular zone in
      patients with ocular histoplasmosis syndrome. DESIGN: Multicenter, randomized,
      controlled clinical trial. SETTING: Ophthalmologic clinics throughout Canada.
      PARTICIPANTS: Patients who provided informed consent, were aged 18 years or
      older, and had extrafoveal membranes associated with ocular histoplasmosis
      syndrome. RESULTS: One hundred forty-one patients were randomized, 134 (95%) of
      whom were determined eligible. Of the eligible patients, 128 (96%) had sufficient
      follow-up for the primary outcome comparison of visual acuity at 1 year. In the
      argon green laser group, there was a mean increase of 3 letters at 1 year, while
      in the krypton red laser group there was a mean decrease of 2.5 letters in visual
      acuity. CONCLUSION: The krypton red laser is no better than the argon green laser
      for the treatment of well-defined extrafoveal choroidal neovascularization
      secondary to ocular histoplasmosis syndrome.

PMID- 7522002
TI  - Recurrent cutaneous necrotizing eosinophilic vasculitis. A novel eosinophil
      mediated syndrome.
AB  - BACKGROUND AND DESIGN: Review of skin biopsy specimens showing necrotizing
      vasculitis revealed three patients with small dermal vessel eosinophilic
      vasculitis and common clinical features characterized by glucocorticoid
      responsive pruritic erythematous, purpuric papules and angioedema associated with
      peripheral blood eosinophilia. Indirect immunofluorescent localization of
      eosinophil granule proteins, neutrophil granule proteins, and mast cell tryptase,
      electron-microscopic evaluation and immunoperoxidase staining for vascular cell
      adhesion molecule type 1, intercellular adhesion molecule type I, endothelial
      leukocyte adhesion molecule type 1, and very-late activation antigen type 4 were
      performed. Eosinophil-active cytokines in serum were evaluated by an eosinophil
      survival assay. OBSERVATIONS: Eight skin biopsy specimens from the three patients
      all showed small-vessel necrotizing vasculitis with exclusive eosinophil
      infiltration. Ultrastructural study demonstrated degenerating eosinophils and
      eosinophil granules in proximity to damaged endothelium. The affected small
      vessels showed marked deposition of the toxic eosinophil granule major basic
      protein in the vessel walls and expression of vascular cell adhesion molecule
      type 1 and intercellular adhesion molecule type 1 on the endothelium with
      adherence of very-late activation antigen type 4-positive eosinophils; E-selectin
      staining was negative. The presence of interleukin 5 in serum available from one
      patient was detected by an eosinophil survival assay. CONCLUSIONS: We studied
      three patients whose cutaneous lesions showed small-vessel eosinophilic
      vasculitis and who presented with recurrent glucocorticoid-responsive pruritic
      purpuric papules and angioedema. The presence of eosinophil-active cytokines in
      serum and the expression of vascular cell adhesion molecule type 1 on the
      endothelium of affected vessels may contribute to the selective adherence and
      localization of activate eosinophils. Subsequent release of cytotoxic proteins
      such as major basic protein may result in destruction of the endothelium in this
      unique syndrome.

PMID- 7522005
TI  - Altered expression of ganglioside phenotypes of human gliomas in vivo and in
      vitro.
AB  - A library of epitope-defined antiganglioside monoclonal antibodies has been used
      to analyze the ganglioside phenotype of human glioma cell lines, rodent
      xenografts derived from them, and a separate panel of human glioma biopsies by
      multiple quantitative and qualitative assays. We have shown that the ganglioside
      phenotypes of cultured cell lines differ from the ganglioside phenotypes in the
      xenografts grown from the parent lines. The lacto series gangliosides 3'-isoLM1
      and 3',6'-isoLD1 are expressed in the majority of primary human central nervous
      system neoplasms and xenografts derived from glioma cell lines, whereas glioma
      cell lines themselves express 3'-isoLM1 and 3',6'-isoLD1 in only 2/15 and 0/15
      cases, respectively. Examination of the ganglioside profiles of serially passaged
      xenografts established from the glioma cell line D-54 MG, which does not express
      the lacto series, revealed the appearance of these gangliosides within one to two
      passages in vivo. The presence of these defined gangliosides in the majority of
      human gliomas and their absence in normal brain supports their application in
      compartmental therapy of primary central nervous system tumors.

PMID- 7522007
TI  - Inhibition of angiogenesis as a strategy for tumor growth control.
AB  - Angiogenesis is a complex sequence of events leading to the formation of new
      capillaries. Although essential to maturation and wound healing, most
      angiogenesis in the adult is associated with pathological events, such as the
      development of solid tumors. One approach to the inhibition of angiogenesis is
      the antagonism of basic fibroblast growth factor, a major angiogenic protein.
      Evidence is reviewed to suggest that inhibiting angiogenesis results in the
      suppression of tumor growth.

PMID- 7522006
TI  - Proteins of the intermediate filament cytoskeleton as markers for astrocytes and
      human astrocytomas.
AB  - There is a pressing need for a more accurate system of classifying human
      astrocytomas, one that is based on morphologic characteristics and that could
      also make use of distinctive biochemical markers. However, little is known about
      the phenotypic characteristics of astrocytomas. Recent studies have shown that
      the expression of proteins comprising the intermediate filament (IF) cytoskeleton
      of astrocytic cells is developmentally regulated. It is our hypothesis that this
      changing protein profile can be used as the basis of a system for clearly and
      objectively classifying astrocytomas. A spectrum of human astrocytomas has been
      examined by immunofluorescence microscopy employing antibodies to several IF
      structural subunit proteins (GFAP, vimentin, and keratins) and an IF-associated
      protein, IFAP-300kDa. These proteins occupy unique temporal niches in the
      cytogenesis of the astrocytic cells: keratins in cells of the neuroectoderm;
      vimentin and IFAP-300kDa in radial glia and immature glia; GFAP in mature
      astrocytes; and vimentin in some mature astrocytes. In agreement with previous
      reports, our immunofluorescence studies have revealed both GFAP and vimentin in
      all astrocytoma specimens. Two new observations, however, are of particular
      interest: IFAP-300kDa is detectable in all astrocytic tumors, and the proportion
      of keratin-containing cells present in the astrocytomas is in direct relationship
      to the degree of the malignancy. Because IFAP-300kDa is not present in either
      normal mature or reactive astrocytes, this protein appears to represent a
      specific marker of transformed (malignant) astrocytes. If it is presumed that
      higher malignancy grades represent the most dedifferentiated cellular state of
      the astrocytes, the presence of keratin-containing cells is not totally
      unexpected, given the ectodermal (epithelial) origin of the CNS. Specific
      developmentally regulated proteins of the IF cytoskeleton thus appear to hold
      great potential as diagnostic markers of astrocytomas and as tools for
      investigating the biology of these tumors.

PMID- 7522004
TI  - Evaluation of argon green vs krypton red laser for photocoagulation of subfoveal
      choroidal neovascularization in the macular photocoagulation study. Macular
      Photocoagulation Study (MPS) Group.
AB  - OBJECTIVE: To evaluate the risks and benefits of argon-green compared with
      krypton red laser photocoagulation in the treatment of subfoveal choroidal
      neovascularization (CNV). DESIGN: Prospective randomized clinical trial assessing
      efficacy of laser treatment vs no treatment in the course of subfoveal CNV.
      Patients randomly assigned to laser treatment were randomly allocated to either
      argon green or krypton red laser photocoagulation. Scheduled follow-up for
      periods up to 5 years was performed. SETTING: Tertiary retinal referral centers.
      PATIENTS: Individuals with age-related macular degeneration and new subfoveal CNV
      or recurrent subfoveal CNV enrolled in the Foveal Photocoagulation Studies of the
      Macular Photocoagulation Study. MAIN OUTCOME MEASURES: Visual acuity, contrast
      sensitivity, reading spread, persistent and/or recurrent CNV, and treatment
      complications. RESULTS: There was no significant difference in average loss of
      visual acuity or contrast sensitivity from baseline levels in eyes treated with
      either wavelength. From baseline, eyes treated with argon green laser in the
      Subfoveal Recurrent CNV Study lost an average of 12 words per minute less than
      eyes treated with krypton red laser. Comparable rates of persistent and recurrent
      CNV were observed in the two laser treatment groups. Focal retinal vascular
      narrowing was more common in eyes treated with argon green laser. CONCLUSIONS:
      Small differences in outcomes favored argon-green treatment of subfoveal CNV, but
      the only statistically significant difference observed between green- and red
      laser treatments was a smaller loss of reading speed among argon green-treated
      eyes in the Recurrent CNV Study. The multiple analyses performed in these two
      Macular Photocoagulation Study trials failed to identify any consistent
      clinically and statistically significant differences between green- or red-laser
      treatment in the management of eyes with subfoveal CNV.

PMID- 7522008
TI  - Altered RNA turnover in carcinogenesis. The diagnostic potential of modified base
      excretion.
AB  - Excretion of urinary modified nucleosides is frequently elevated in patients with
      oncogenic disease. Increases of urinary pseudouridine excretion are now
      demonstrated in patients with a variety of brain tumors. The potential use of
      urinary modified base excretion as a cancer marker is discussed and possible
      sources of the elevated nucleosides are detailed. The specific steps in RNA
      metabolism that result in increased levels of RNA nucleoside excretion are poorly
      understood. This knowledge will be necessary to understand the molecular
      mechanism and the clinical significance of urinary nucleoside excretion in
      treatment and diagnosis of oncogenic disease.

PMID- 7522009
TI  - T cells as antigen-presenting cells.
AB  - Human T cells express major histocompatibility complex (MHC) class II antigens
      and adhesion molecules characteristic of antigen-presenting cells (APCs), and
      recent in vitro and in vivo evidence supports an antigen-presenting function for
      T cells. In this guise, T cells provide downregulatory signals for the immune
      response by inducing anergy in T cells that have already been activated and
      cytotoxicity in resting T cells. Here, Werner Pichler and Tony Wyss-Coray suggest
      that this may represent an important negative mechanism for T-cell homeostasis.

PMID- 7522010
TI  - The B7 and CD28 receptor families.
AB  - Current evidence suggests that T-cell receptor (TCR) recognition of antigen bound
      to the major histocompatibility complex (Ag-MHC) is insufficient to lead to T
      cell proliferation or effector function. For a helper T cell to produce
      sufficient interleukin 2 (IL-2) to allow autocrine-driven clonal expansion, there
      is a requirement for so-called 'co-stimulatory' or 'accessory' signals in
      addition to TCR ligation by Ag-MHC. The interaction of the CD28 receptor on T
      cells with B7 on antigen-presenting cells (APCs) supplies one such co-stimulatory
      signal. However, the recent discovery that CD28 and B7 are each members of larger
      gene families suggests that the regulation of co-stimulation is more complex than
      previously imagined. Here, Carl June and colleagues highlight recent advances in
      the understanding of the CD28 and B7 receptor families.

PMID- 7522011
TI  - [The pork-cat syndrome or crossed allergy between pork meat and cat epithelia
      (2)].
AB  - Is there a port-cat syndrome in food allergy? Many clinical observations have
      revealed a frequent association between allergy to cat epithelia in subjects who
      have allergy to pork meat. This second part, from clinical tests such as skin
      tests and laboratory tests such as CAP RAST, electrophoresis, Western blot and
      chromatography, confirms the existence of a crossed reaction between pork meat
      and cat extract. This crossed reaction is linked with a common epitope. A common
      protein has been found that has a molecular weight of 67,000 d. for subjects who
      are sensitive to cat extracts and pork meat.

PMID- 7522012
TI  - [Alimentary anaphylactic shock: implication of penicillin residues].
AB  - The case of a 64 y.o. female is reported. She experienced formerly four
      anaphylactic shocks. Two shocks occurred after ingestion of pork and beef meat.
      Any food allergy to animal proteins was discarded. A high degree of sensitivity
      to penicillin G was proved by a positive prick test to penicillin G 1 Ul/ml,
      which induced a systemic reaction. RAST to penicillin G was class 4. The
      leucocyte histamine release test showed a high level of spontaneous histamine
      release. A double blind, placebo controlled, oral challenge with penicillin mixed
      to milk induced wheezing and a fall of blood pressure at the cumulative dose of
      20 Ul. The hypothesis of food induced anaphylaxis, linked to penicillin residues
      in meats, is highly plausible. The significance of the phenomenon of spontaneous
      histamine release is discussed. It might point to frequent ingestions of hidden
      penicillin residues in the diet.

PMID- 7522014
TI  - Efficacy of different proteolytic treatments for the immunohistochemical stain of
      cytokeratins.
AB  - Aim of the present study was to investigate the efficacy of 4 different
      proteolytic treatments (Ficin, Protease type XIV, Microwave irradiation in
      Citrate buffer and Microwave irradiation in Lead Tiocyanate), compared to the
      incubation with buffer only, for the detection of cytokeratins in 10 cases of
      carcinomas from different organs. The same anti-cytokeratin antibody was applied
      to two sets of tissue sections, after proteolytic treatment, and the reaction was
      developed by using a different method (ABC or APAAP) for each set of slides. The
      semiquantitative evaluation of the specimens demonstrated that the higher number
      of immunoreactive tumor cells was present after Microwave irradiation in Lead
      Tiocyanate and, to quite a lesser extent, in Citrate buffer. Ficin and Protease
      type XIV appeared less effective and in some circumstances, the enzymatic
      digestion of tumor cells seemed to negatively affect the quality of immunostain.
      When buffer only was used the percentage of immunoreactive tumor cells was
      considered to be unreliable for diagnostic purposes. The results of the study
      seem to suggest that proteolytic pretreatment is essential to avoid false
      negative results when cytokeratin immunostain is essential in histopathology and
      that Microwave irradiation in Citrate buffer is eligible as the best procedure.

PMID- 7522015
TI  - Induction of intercellular adhesion molecule-1 by lipopolysaccharide in canine
      alveolar macrophages.
AB  - Previous studies have demonstrated that alveolar macrophages (AMphis) adherent to
      plastic release interleukin-8 in response to lipopolysaccharide (LPS). We sought
      to determine whether LPS could also alter surface adhesion molecule expression
      and thus modulate additional AMphi adhesive interactions. Canine AMphis obtained
      by bronchoalveolar lavage of excised lung were adhered onto tissue culture
      plastic and exposed to LPS (0.01 to 100 ng/ml). Expression of beta 2 integrins
      and intercellular adhesion molecule-1 (ICAM-1) was subsequently determined by
      flow cytometry, a cDNA probe to canine ICAM-1 was used to quantify ICAM-1 mRNA,
      and changes in adhesion molecule function were assessed by evaluating the extent
      of homotypic aggregation. ICAM-1 and CD11a/CD18 were present on freshly isolated
      AMphis. CD11b/CD18 and CD11c/CD18 were expressed at lower levels. Nonadherent
      AMphis expressed a pattern of beta 2 integrin and ICAM-1 comparable to adherent
      cells. During short-term LPS stimulation (3 h), adherent AMphis increased both
      the synthesis and expression of ICAM-1. CD18 expression was either decreased or
      remained unchanged with LPS stimulation. LPS stimulation in vitro (> 0.01 ng/ml)
      enhanced the homotypic aggregation of adherent AMphis. Aggregation was blocked by
      monoclonal antibodies to ICAM-1 (CL18/6) and CD11a (R7.1) and CD18 (R15.7).
      Similar kinetics were found for expression of ICAM-1 and homotypic aggregation,
      suggesting that up-regulation of ICAM-1 is a major determinant of the LPS
      stimulated aggregation of AMphis.

PMID- 7522013
TI  - Transmissible cerebral amyloidoses as a model for Alzheimer's disease. An
      ultrastructural perspective.
AB  - Alzheimer's disease, a prototypic nontransmissible cerebral amyloidosis, has no
      adequate experimental model. Several pathogenetic events, however, may be modeled
      and accurately studied in the transmissible cerebral amyloidoses of kuru,
      Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, and scrapie.
      The common neuropathological denominator in both types of cerebral amyloidoses is
      the presence of stellate kuru plaques, senile plaques, and pure neuritic plaques.
      These amyloid plaques consist of amyloid fibers, dystrophic neurites, and
      reactive astrocytes in different proportions. Microglial cells, which are
      regarded as amyloid producer/processor cells in Alzheimer's disease, may play the
      same function in the transmissible cerebral amyloidoses. In both transmissible
      and nontransmissible amyloidoses, the impairment of axonal transport leads to
      accumulation of abnormally phosphorylated cytoskeleton proteins (such as
      neurofilament proteins and microtubule-associated protein tau), which eventually
      produce dystrophic neurites observed as parts of plaque or as isolated
      pathological structures.

PMID- 7522016
TI  - Chymotryptic activity in perfusates of isolated rat trachea: correlation with
      mucosal and connective tissue mast cell secretion.
AB  - Serine proteinases participate in many inflammatory events in the airway. We
      therefore screened perfusates of isolated rat tracheas for tryptic, elastolytic,
      and chymotryptic serine proteinases. Only chymotryptic activity, indicated by
      hydrolysis of the synthetic substrate N-succinylalanylalanylprolylphenylalanyl p
      nitroaniline (AAPF), was consistently detected in these perfusates. Basal levels
      of chymotryptic activity were not increased significantly by electrical field
      stimulation (EFS) (mean change +/- SEM: -0.05 +/- 0.05 m o.d. units, n = 4) or by
      10(-7) M substance P (SP) (+0.04 +/- 0.02 m o.d. units, n = 14). However, the
      mean change after the stimuli were jointly administered (0.17 +/- 0.06 m o.d.
      units, n = 12) was significantly greater than control or after EFS (P = 0.01, one
      way ANOVA). The SP + EFS-induced chymotryptic activity was inhibited by PMSF,
      soybean trypsin inhibitor, and chymostatin and was associated with an increase in
      histamine concentration and immunoreactivity to rat mast cell proteases (RMCP),
      indicating that the activity is due to mast cell degranulation. However, the
      activity was not significantly decreased by pretreating rats with systemic
      compound 48/80. SP + EFS-induced chymotryptic activity peaked rapidly and was
      associated with modest histamine release and an immediate peak in
      immunoreactivity to RMCP II, a marker of mucosal mast cells. Immunoreactivity to
      RMCP I, a marker of connective tissue mast cells, also increased after SP + EFS,
      but this immunoreactivity was either delayed or more sustained and did not
      coincide with the peak of chymotryptic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522019
TI  - Molecular cloning of HCV and clinical application.
AB  - Fifty-five clones encoding epitopes of HCV were isolated from Japanese patients.
      Their amino acid homology (AAH) to the sequence of prototype (HCV-1) ranged from
      47% to 94%. These sequences cover 60% of the HCV genome lacking M/E and NS2
      regions suggesting a very low or lacking immunogenicity for these regions. Two
      test kits for detection of anti-HCV antibody were developed using a combination
      of a synthetic peptide (AR142) containing the epitope of N14 (QRKTKRSTNRR) having
      a homology to the core of HCV of 8/11AA and a non-fusion recombinant protein Y19
      starting from amino acid number (AAN) 1380 to 1507 in the NS3 region showing a
      AAH to the HCV-1 of 90%, and a combination of a mixture of three synthetic
      peptides of S29 AAN of 1-30, 38-65 and 47-74 of the core and a non-fused
      recombinant protein S4 AAN of 1287-1506 having a 93% AAH of the NS3 region. They
      showed almost the same order of sensitivity and specificity of the second
      generation kits when tested with serum from blood donors and patients with non-A,
      non-B hepatitis. It should also be stressed that in all of the complete
      responders of a recombinant alpha-interferon therapy, the antibody levels against
      AR142 gradually decreased during and after the treatment. In 1992, studies
      performed for 125 patients with hepatocellular carcinoma in our clinic shows that
      of these 16 patients might developed from either chronic non-B, non-C liver
      diseases or chronic liver diseases caused by mutant(s) of HCV as their serum were
      negative for HBsAg and second-generation of anti-HCV.

PMID- 7522018
TI  - Aprotinin inhibits fibrinolysis, improves platelet adhesion and reduces blood
      loss. Results of a double-blind randomized clinical trial.
AB  - The present recommendation is that aprotinin should be started before cardiac
      surgery, but as bleeding is only a problem in a minority, most patients are
      treated unnecessarily. In a prospective, randomised, double-blind trial we have
      studied the use of aprotinin, given only to the minority of patients who bled
      significantly post-operatively and who had not received prophylactic aprotinin.
      Sixty patients, who bled in excess of 400 ml in the first 3 h post-operatively
      were randomised to receive either aprotinin (2 x 10(6) KIU loading dose followed
      by an infusion of 0.5 x 10(6) KIU/h for 4 h) or placebo, in addition to
      conventional treatment. The demographic characteristics and the surgical
      procedures performed were similar in the two groups. Haematological variables
      were measured (A) before and (B) at the end of the infusion. Three patients were
      re-explored for excessive bleeding in each group and one patient died in each
      group. The patients in the aprotinin group bled significantly less and had higher
      haemoglobin levels on discharge than the patients in the placebo group. The
      tissue plasminogen activator antigen decreased and the fibrinogen level increased
      in the aprotinin group. In addition, aprotinin increased the number of surface
      GPIb platelet receptors as estimated by flow cytometry (36% versus 5%, P < 0.01)
      and maintained the platelet von Willebrand Factor activity (vWF). There was no
      significant difference in D-dimers, fibrin(ogen) degradation products, plasma vWF
      activity and antigen, platelet vWF antigen, platelet aggregation (to collagen,
      arachidonic acid, platelet activating factor and ristocetin), platelet count or
      transfusion of blood products between the two groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7522020
TI  - ELISA in serodiagnosis of HCV infection.
AB  - A high level of anti-HCV is generally associated with viral replication and the
      number of recognized epitopes appears to be correlated with the viral charge.
      Nevertheless, the absence of detectable antibodies in about 60% of patients
      during the acute phase of the disease and in 10% of chronically infected
      (generally immunocompromised subjects) are heavy handicaps for HCV serology.
      Moreover, low levels of anti-HCV antibodies can persist after complete recovery,
      and HCV viremia does not appear to be associated with the presence of a special
      antibody specificity. The immunoblots presented as 'confirmatory test' always
      appear to be less sensitive than the screening tests and therefore are unable to
      discriminate between post-infection antibodies and false-positive reactions, as
      rare as they can be. In these cases, as in non-responder patients, PCR appears
      essential. The possible reasons of immune response limitations and the possible
      improvements of HCV serology are discussed.

PMID- 7522017
TI  - Is there a phase of hypercoagulability when aprotinin is used in cardiac surgery?
AB  - To determine a possible phase of hypercoagulability after the use of high-dose
      aprotinin, a prospective randomized double-blind study was performed. Twenty
      patients undergoing aortocoronary bypass surgery were investigated, a placebo
      group P (n = 10) was compared to an aprotinin group A (n = 10). Examining
      parameters of thrombin activation and fibrinolysis, we found during
      extracorporeal circulation--under continuous aprotinin infusion--a significant
      inhibition of thrombin activation and fibrinolysis in the aprotinin group
      (thrombin-antithrombin-III-complexes: 95 +/- 23 micrograms/l, d-dimers: 448 +/-
      60 ng/ml, plasminogen activity: 33 +/- 3%, plasminogen activator inhibitor: 98 +/
      14 U/ml) compared to the placebo group (thrombin-antithrombin-III-complexes: 143
      +/- 13 micrograms/l, d-dimers: 2755 +/- 430 ng/ml, plasminogen activity: 125 +/-
      15%, plasminogen activator inhibitor: 10 +/- 4 U/ml). In contrast, after stopping
      the aprotinin infusion--from the end of extracorporeal circulation until the
      morning of the first postoperative day--strong thrombin activation took place in
      the aprotinin group (d-dimers increased from 472 +/- 90 to 1607 +/- 140 ng/ml),
      while in the placebo group a decrease could be registered. At this time, the
      fibrinolysis was still reduced in the aprotinin group (plasminogen activity: 48
      +/- 6% vs 85 +/- 16% in the placebo group). In conclusion, interference with the
      thrombohemorrhagic balance induces hypercoagulability after the use of high-dose
      aprotinin, with elevated levels of thrombin-antithrombin-III-complexes, d-dimers,
      and plasminogen and a decreased level of plasminogen activator inhibitor. In our
      opinion, it is necessary to prevent this counter-regulation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7522021
TI  - The polymerase chain reaction and hepatitis C virus diagnosis.
AB  - In the absence of tissue culture, electron microscopy or assays for viral
      antigen, the direct detection of hepatitis C virus (HCV) is by necessity
      dependent upon nucleic acid hybridisation methods. Of the available methods,
      amplification of HCV cDNA by polymerase chain reaction (PCR) commends itself by
      virtue of its extreme sensitivity and its consequent ability to detect the very
      low levels of HCV-RNA that are present in many clinical samples. In this review
      the development and evolution of PCR techniques for HCV detection are described
      and a number of clinical applications are considered in detail. The applications
      include diagnosis of acute infection during the seronegative window period prior
      to the appearance of HCV antibodies, and diagnosis of HCV infection in the
      immunosuppressed. PCR also enables identification of the chronic viraemic carrier
      state and it permits accurate monitoring of the antiviral effects of drugs such
      as interferon. Confirmation of the specificity of HCV antibody assays and
      detection of HCV contamination of blood donations and blood products are other
      important areas in which PCR techniques have proved invaluable. In addition, PCR
      based techniques underlie an increasing number of molecular epidemiological and
      genotyping studies and they are providing insights into the details of HCV
      cellular tropism and replication. A number of logistic problems and operational
      difficulties are also discussed. Despite these limitations it is concluded that
      PCR will continue to make significant contributions to both clinical practice and
      to our understanding of the basic biology of HCV infection.

PMID- 7522022
TI  - Hepatitis C virus infection from blood and blood products.
AB  - The addition of second-generation HCV epitopes in antibody detection assays has
      increased the sensitivity and specificity of blood donor testing, to prevent post
      transfusion hepatitis non-A, non-B (PTH-NANB), later characterized as Hepatitis
      C. However, it is not clear whether all HCV infectious donors are detected by
      second-generation anti-HCV testing. Prospective studies on PTH-NANB were left
      with some unresolved cases. The use of second-generation anti-HCV assays in blood
      banks presented a problem with a relatively large number of indeterminate
      reactivities in supplemental assay such as RIBA-2. These indeterminate
      reactivities may be solved by the use of polymerase chain reaction (PCR). PCR is
      more and more used as an extra confirmatory assay to resolve RIBA indeterminate
      results on blood donors. However, a European study on the proficiency of HCV PCR
      in different countries revealed that only a minority of the reference
      laboratories perform this test faultless. Lately, third-generation RIBA was
      developed, which was originally designed to resolve RIBA-2 indeterminate cases.
      RIBA-3 was shown to be more sensitive and specific in early HCV infection and
      blood donors than RIBA-2. Third-generation anti-HCV testing will become standard
      practice. Some questions, however, remain unanswered. Do we miss any rare HCV
      infectious donors, of other genotypes, with third-generation assays, based only
      on the type 1 sequence of HCV? Can we improve HCV detection in the early phase of
      infection? What is the role of sporadic HCV transmission? How can we standardize
      HCV nucleic acid detection methods?

PMID- 7522023
TI  - Seroepidemiology of hepatitis C virus infection in Japan and HCV infection in
      haemodialysis patients.
AB  - Since January 1990, Japanese Red Cross Blood Centres have introduced hepatitis C
      virus screening with a first-generation ELISA. From April to December 1992,
      approximately 0.98% among 10,905,489 blood donations screened by a second
      generation assay were anti-HCV-positive in all Japan. Seropositivity of anti-HCV
      increased with the age and serum transaminase value in both sexes. In blood
      donors having a history of transfusion, the anti-HCV reactive rate was 7.4%. The
      results of the study made by the Japanese Red Cross Non-A, Non-B Hepatitis
      Research Group show the effectiveness of implementation of HCV screening to
      prevent posttransfusion hepatitis. Consecutive haemodialysis patients with
      chronic renal failure are at risk for infection by a variety of blood-borne
      agents transmitted within dialysis units. Because of their immunocompromised
      state, they frequently also have an unusual susceptibility to a variety of
      nosocomial infections, such as HBV, HCV, and HTLV-I. We tested the prevalence of
      anti-HCV in 1423 (848 males and 575 females) haemodialysis patients from 18
      hospitals in Kumamoto Prefecture, Japan, using the Ortho first generation anti
      HCV screening assay. There were 316 patients (22.2%) positive for HCV antibodies.
      The second-generation test was positive in most haemodialysis patients who were
      reactive to the first-generation assay. The prevalence of HCV infection increased
      with the duration of haemodialysis, yet there was a high frequency of HCV
      seropositivity even without blood transfusion. Acquisition of HCV in dialysis
      patients could be explained by HCV infection within the unit other than by blood
      (all haemodialysis are done with disposable kits, syringes, and needles), by
      secondary HCV infection after the immunodeficiency of haemodialysis, or by HCV
      infection of the kidney or glomerular deposition of immune HCV/anti-HCV complexes
      leading to chronic renal failure (as with HBV infection of the liver and kidney.

PMID- 7522024
TI  - Hepatitis C virus infection and liver disease: peculiar epidemiological and
      clinicopathological features.
AB  - Hepatitis C virus (HCV) infection is associated with a wide spectrum of liver
      disease ranging from asymptomatic carriage to severe forms of chronic hepatitis.
      HCV is not invariably pathogenic and genetic heterogeneity of HCV could be a
      major cause of such a variability. In clinical practice this means that presence
      and replication of the virus do not invariably imply a virus-induced liver
      damage. IgM antibodies that are the best diagnostic tools for the other forms of
      viral hepatitis are not sensitive and specific enough for hepatitis C, therefore
      we have to look for alternatives. Detection of anti-HCV does not help to
      distinguish past from present infections and only anti-HCV seroconversion in
      previously negative patients can indicate a recent HCV infection. However, the
      significant association between serum anti-C100-3 and HCV-RNA suggests that anti
      HCV can be considered an indirect marker of HCV infectivity. In anti-HCV-negative
      infections and early acute hepatitis cases HCV-RNA detection will represent a
      valid diagnostic alternative. In patients undergoing antiviral therapy monitoring
      anti-HCV by immunoblotting assays and HCV-RNA by quantitative assays represent a
      valid tool to predict response that invariably has occurred in patients who had
      undetectable serum HCV-RNA and/or decreasing anti-HCV titres. Assays that detect
      multiple anti-HCV antibodies all together appear unsuitable for monitoring
      because they miss the disappearance of single antibodies. Anti-C22 appears the
      most frequent and earliest to be detected and usually it has the highest titre.
      Anti-C100 titres decrease earlier than anti-C33 and anti-C22 in patients with
      chronic HCV hepatitis who respond to antiviral therapy. The natural course of HCV
      infection appears to be characterized by three consecutive phases: disease,
      asymptomatic carrier and recovery. If transition from the first to the last
      occurs very slowly or the disease phase persists for years it may warrant in
      susceptible hosts severe forms of liver disease.

PMID- 7522025
TI  - Epidemiology of hepatitis C virus in Europe.
AB  - Epidemiology of Hepatitis C virus (HCV) infection in Europe is changing very
      rapidly since the main source of contamination was blood transfusion and the use
      of surrogate markers allowed to diminish dramatically the number of patients
      contaminated through HCV post transfusion hepatitis. The recent description of
      several genotypes with different distributions over Europe and different
      pathogenicity will allow to explain various evolutive aspects of the disease. At
      present, groups at risk are drug addicts (70%), hemophiliacs (contaminated with
      blood products before 1985), hemodialysis patients (20%) and patients with
      cirrhosis with or without hepatocellular carcinoma. The detection of HCV markers
      prior to blood transfusion allowed to detect asymptomatic carriers of HCV, some
      of them with latent chronic hepatitis which can be predicted by the detection of
      HCV RNA in the serum. Vertical and sexual transmission are rare but possible
      events observed with certainty in patients co-infected with HIV and controversial
      in other situations.

PMID- 7522026
TI  - Human placental mast cells as an in vitro model system in aspects of neuro
      immunotoxicity testing.
AB  - 1. In both the developing and adult nervous systems, nerve growth factor (NGF)
      influences neuronal survival, differentiation and recovery following insult. 2.
      The effect of NGF upon human placental mast cells (HPMC) was investigated, since
      it is known that rodent mast cells express a functional receptor for NGF and
      secrete histamine upon challenge with this neurotrophic factor. Furthermore,
      human placental tissue contains a significant amount of NGF and expresses a NGF
      receptor. 3. HPMC were shown to secrete histamine in a concentration dependent
      manner in response to NGF (0.001-10.0 micrograms ml-1) in the presence of the
      lipid cofactor phosphatidylserine (10.0 micrograms ml-1). 4. NGF induced
      histamine release from isolated HPMC with an EC50 of 0.1 microgram ml-1 NGF and
      maximal secretion of total cellular histamine of 22.3 +/- 3.4% at 3.0 micrograms
      ml-1. 5. The response was shown to be a secretory process, dependent upon the
      presence of exogenous calcium ions and to be pH- and temperature-sensitive. 6.
      HPMC are suggested to be a suitable primary cell model for use in aspects of in
      vitro toxicity testing, in terms of assessing the neuro-immunotoxic potential of
      neurotrophic therapeutics. In addition, mechanistic studies concerning those
      xenobiotics which may exert their neurotoxic effect via interaction with
      neurotrophic factors and, or their receptors, may be studied in this human cell
      model.

PMID- 7522027
TI  - The inner-core, outer-core and capsule cells of the human Pacinian corpuscles: an
      immunohistochemical study.
AB  - The distribution of several markers for Schwann cells and perineurial cells,
      including S-100 protein, Leu-7 antigen, vimentin and epithelial membrane antigen
      was studied immunohistochemically in Pacinian corpuscles from human digital skin.
      Formaldehyde fixed paraffin embedded tissues, and monoclonal antibodies were
      used. A positive immunostaining for S-100 protein, Leu-7 antigen and vimentin was
      found in the inner-core cells, whereas the outer-core and capsule lamellae were
      labelled for both epithelial membrane antigen and vimentin. The pattern of
      vimentin immunoreactivity was not homogeneous but focally distributed, and
      occasionally, positive immunoreactivity for vimentin was observed in blood
      vessels supplying the capsule. Present results provide evidence that some
      antibodies against Schwann cells and perineurial fibroblastic cells, selectively
      stain the Pacinian corpuscles derivatives while others are commonly expressed for
      non-neuronal cells of sensory nerve corpuscles.

PMID- 7522029
TI  - Mortality from accidents and violence in the Americas.

PMID- 7522030
TI  - Endotoxin is angiogenic.
AB  - The formation of new blood vessels, angiogenesis, is an important event in
      inflammation, wound healing and tumour growth. Mediators produced by various
      cells when exposed to endotoxin include cytokines (tumour necrosis factor,
      interleukins 1 and 6, and basic fibroblast growth factor) which, it has been
      suggested, stimulate angiogenesis. The angiogenic effect of endotoxin
      (lipopolysaccharide, LPS) was studied in rats using the quantitative mesenteric
      window assay. Adult rats were injected intraperitoneally with Escherichia coli
      LPS (5 pg/ml-20,000 ng/ml) twice daily for 4.5 consecutive days and were
      sacrificed 14 days after the start of this treatment. An angiogenic response was
      observed at concentrations of > 2 ng/ml in a dose-dependent manner. No
      inflammatory cellular exudate was seen in the test tissue at the time of
      angiogenesis analysis. Suppressed body-weight gain, a marker of the systemic
      effect of LPS in the rat, was significant only at the highest dose tested. The
      data suggest that endotoxin-mediated neovascularization could be a component of
      inflammation and wound healing.

PMID- 7522031
TI  - A morphometric method to evaluate angiogenesis kinetics in the rat mesentery.
AB  - The mesenteric window angiogenesis assay permits the objective determination of a
      number of angiogenesis parameters in peritoneal connective tissue. The time
      course of the angiogenic response that follows activation of endogenous
      connective tissue mast cells in situ in normal adult rats was investigated using
      a set of quantitative variables. A method developed to quantify angiogenesis
      kinetics by evaluation of microvascular ramification and elongation is presented.
      The angiogenic process was found to proceed long after the termination of the
      inducing selective mast-cell activation and was thus to a large extent self
      perpetuating. The angiogenesis also continued long after the maximum level of the
      ingrowth of vessels from adjacent tissues, the vessel density, and ramification
      within the vascularized areas was reached. The whole angiogenic phase lasted as
      long as 5-6 weeks and the total vessel density, i.e. the vascular area multiplied
      by the vessel density, remained elevated over controls throughout the course of
      the 99-day experiment. It appears that angiogenesis kinetics based on truly
      quantitative assessment of relevant parameters, as in the present study, will be
      a useful means in elucidating how positive and negative angiogenic factors,
      individually or in combination, influence the microvascular arborization.

PMID- 7522032
TI  - Differences in transcription and promoters of Xmrk-1 and Xmrk-2 genes suggest a
      role for Xmrk-2 in pigment pattern development in the platyfish, Xiphophorus
      maculatus.
AB  - Pigment (macromelanophore) patterns in the platyfish Xiphophorus maculatus are
      due to a complex pigmentary locus; for example, the spotted-dorsal (Sd) fin
      pattern is due to the Sd locus. In interspecific backcross hybrids with the
      swordtail X. helleri, the Sd pattern changes into benign or malignant dorsal fin
      melanoma as a result of hemi- or homozygous loss of a platyfish regulatory (R)
      gene, the tumor suppressor gene Diff, that appears to play a role in the final
      differentiation of macromelanophores. Closely linked to the pigmentary locus is
      an epidermal growth factor receptor-like gene, Xmrk-2, that has arisen by
      duplication from the linked Xmrk-1. The transcriptional expression of the Xmrk
      genes was determined in various tissues including Sd pigment patterns and
      melanomas of various growth potential using reverse transcription-polymerase
      chain reaction. While Xmrk-1 expression was found in all tissues examined, Xmrk-2
      expression correlated with pigment cell growth. Xmrk-2 was highly expressed in
      the dorsal fin exhibiting the Sd pattern but drastically reduced in a platyfish
      mutant which has lost the capacity to form these pigment cells in the dorsal fin.
      Most interestingly, Xmrk-2 expression increased with the proliferative capacity
      of the melanomas but declined once melanoma growth ceased. We conclude that Xmrk
      2 plays a role in the formation of the pigment pattern cell type, perhaps in
      proliferation of precursor cells, which, in melanoma, are kept in a proliferative
      state due to loss of Diff.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522028
TI  - Antigen retrieval and microwaving.

PMID- 7522033
TI  - Whey acidic protein extrinsically expressed from the mouse mammary tumor virus
      long terminal repeat results in hyperplasia of the coagulation gland epithelium
      and impaired mammary development.
AB  - The whey acidic protein (WAP) is a milk protein that contains a cysteine-rich
      motif. This characteristic WAP signature has also been found in some protease
      inhibitors and certain proteins involved in tissue modeling. WAP is specifically
      synthesized in mammary tissue from late pregnant and lactating animals, and
      precocious synthesis results in impaired lobuloalveolar development of the gland
      in some transgenic lines. To determine whether growth modulatory effects of WAP
      are confined to mammary tissue, we expressed the WAP gene under the control of
      the mouse mammary tumor virus long terminal repeat in transgenic mice. The
      transgene was expressed at high levels in organs with exocrine function, such as
      mammary and salivary glands, prostate, seminal vesicle, and the coagulation
      gland. In addition to impaired mammary development, we observed hyperplasia and
      dysplasia of the coagulation gland epithelium. These findings suggest that WAP or
      a member of the WAP signature family can, in certain tissue contexts, function as
      an epithelial growth regulator. It appears from the present study that growth
      regulatory effects of WAP are restricted in the mouse to the mammary and
      coagulation gland epithelium.

PMID- 7522034
TI  - Cell cycle-dependent expression of Nek2, a novel human protein kinase related to
      the NIMA mitotic regulator of Aspergillus nidulans.
AB  - The serine/threonine protein kinase NIMA of Aspergillus nidulans is required for
      entry into mitosis and may function in parallel to the universal mitotic inducer
      p34cdc2. Here, we report the isolation of complementary DNAs encoding Nek2 and
      Nek3, two novel human protein kinases structurally related to NIMA. Sequence
      comparisons revealed several unique features which may define a family of NIMA
      related protein kinases. Nek2 was chosen for further study since it represents
      the closest known mammalian relative of NIMA. Chromosomal mapping of the nek2
      gene identified two independent loci on chromosomes 1 and 14, and Northern blot
      analyses revealed the expression of two distinct mRNAs of approximately 2.4 and
      4.7 kilobases in all human cell lines examined. In HeLa cells synchronized by
      both drug arrest and elutriation, a strikingly cell cycle-dependent pattern of
      Nek2 expression could be observed; Nek2 protein was almost undetectable during G1
      but accumulated progressively throughout S, reaching maximal levels in late G2.
      These observations demonstrate that Nek2 resembles Aspergillus NIMA, not only in
      its catalytic domain, but also in its cell cycle-dependent expression. Hence, the
      human Nek2 protein kinase may also function at the onset of mitosis.

PMID- 7522035
TI  - Transgenic mice expressing targeted HPV-18 E6 and E7 oncogenes in the epidermis
      develop verrucous lesions and spontaneous, rasHa-activated papillomas.
AB  - In order to create a transgenic model for human papilloma virus (HPV)-associated
      carcinogenesis, we have used the regulatory elements of a human keratin K1 (HK1)
      gene to target the expression of the E6 and E7 oncogenes of HPV-18 exclusively to
      the epidermis. All murine expressors were viable and lived normal lifetimes;
      older mice (> 1 year) possessed numerous small lesions with a verrucous (wart
      like) histotype. Analysis of newborn epidermis and lesions revealed that the HPV
      18 E6/E7 genes were being expressed with a predominance of the E6*/E7 transcript
      over the full length E6/E7 message. The long latency in lesion appearance may
      reflect the low level of intact E6 transcripts and the requirement for additional
      genetic or epigenetic events before production of an overt lesion. In agreement
      with this proposal, spontaneous papillomas developed that expressed an activated
      rasHa oncogene (codon 61, A-->T; codon 13, G-->T). All lesions expressed keratin
      genes K1, K6, and K13 in a fashion characteristic of hyperproliferative or benign
      tumors with no evidence of malignant conversion. Our results demonstrate that the
      mouse epidermis represents a relevant in vivo model system to analyze the
      interaction between HPV and cellular genes in neoplasia.

PMID- 7522036
TI  - The clinical staging of rectal cancer in patients treated by preoperative
      radiotherapy.
AB  - We describe the results of clinical and (or) surgical staging used by the same
      surgeon to select a group of 41 patients with advanced rectal cancer for
      preoperative radiotherapy. Fifteen patients with resectable but advanced rectal
      cancer were subjected to a short course of radiotherapy (30 Gy in 10 days),
      immediately followed by resection. High dose preoperative radiotherapy (50-56 Gy
      in 5 weeks) was administered to 26 patients with borderline resectable or fixed
      cancer. Adequate resection of the tumour was possible in 21 of these 26 patients
      4 weeks after the end of the radiotherapy. A total of 36 patients thus underwent
      resection after preoperative radiotherapy. No radiotherapy related acute or late
      morbidity was seen. On 31 December 1992 the results were investigated
      retrospectively. The median time since entering into the study was 87 months
      (range 27-141). During the follow-up, pelvic recurrence was detected in six
      patients; one patient had concomitant distant metastases. The local recurrence
      free survival at 5 years calculated by the Kaplan-Meier method was 72% (95% CI 58
      85). Distant metastases without local recurrence developed in 11 patients. The
      calculated survival at 5 years was 45% (95% CI 30.5-59).

PMID- 7522038
TI  - Detection of DNA amplification in 17 primary breast carcinomas with homogeneously
      staining regions by a modified comparative genomic hybridization technique.
AB  - A modified comparative genomic hybridization (mCGH) technique was applied to a
      series of 17 primary breast carcinomas in which cytogenetic study (CG)
      demonstrated the presence of homogeneously staining region(s), suggesting the
      occurrence of DNA amplification. mCGH demonstrated recurrent amplifications of
      the whole chromosome arms 8q (9 times) and 1q (7 times) and of DNA loci in the
      following bands: 11q13 (6 times), 9p13 and 17q21.1 (4 times), 1q21.1 and 16p11.2
      (3 times), and 8q22, 8q24.1, 10q22, 15q26, 17q23, and 20q13.3 (twice).
      Amplification of whole chromosome arms is likely to have resulted from unbalanced
      translocations or isochromosomes, whereas amplifications of smaller chromosomal
      segments probably arose through real DNA amplification processes. In all tumors
      but one, more than one amplified locus was detected. The fact that many
      chromosomal sites were involved suggests that the process of amplification is
      complex and that many genes are potential targets.

PMID- 7522037
TI  - Loss of chromosome arm 8p loci in prostate cancer: mapping by quantitative
      allelic imbalance.
AB  - A previous study of 18 primary or metastatic prostate cancers showed loss of
      genetic markers on chromosome 8; 10, or 16 in more than 50% of cases [Bergerheim
      USR et al. (1991) Genes Chromosom Cancer 3:215-220]. The small size and
      infiltrative nature of primary prostatic tumors have hindered efforts to assess
      allelic losses by traditional restriction fragment length polymorphism
      (RFLP)/Southern blotting methods. To improve the sensitivity and specificity of
      this analysis in early prostate cancer, we have amplified polymorphic
      microsatellite repeats by polymerase chain reaction (PCR), and have quantitated
      allelic imbalances with phosphor imaging technology. In this study, 63 primary
      prostate tumors and matched benign tissues obtained by radical prostatectomy were
      examined at 28 genetic loci on chromosome 8, all but five of which were located
      on the short arm. Twenty-nine (46%) of the 63 cases showed loss of at least one
      locus. Multiple adjacent loci, usually including the LPL and MSR genes in 8p22,
      were lost in 28 cases. In 10 of these, losses were observed at all informative
      loci on the p arm. In another 15 tumors, losses were restricted to subregions of
      the p arm by loci retained either distally toward the p terminus or proximally at
      the 8p12-8p21 border, or both. In three tumors, two discrete regions of loss were
      observed within 8p, separated by several retained loci. Allelic loss of 8p loci
      was associated with higher tumor grade. These data are complementary to previous
      reports of allelic deletions in colorectal, hepatocellular, and non-small cell
      lung cancers and suggest the existence of one or more pleotropic tumor suppressor
      genes on 8p.

PMID- 7522040
TI  - Allelotype study of esophageal carcinoma.
AB  - To investigate genetic features of esophageal cancer, we have examined 93
      squamous cell carcinomas of the esophagus for loss of heterozygosity (LOH), using
      41 restriction fragment length polymorphism (RFLP) markers representing all
      autosomal chromosomes. Allelic losses at frequencies of at least 30% were
      observed at loci on chromosomal arms 3p (35%), 3q (30%), 5q (36%), 9p (57%), 9q
      (60%), 10p (33%), 13q (43%), 17p (62%), 17q (46%), 18q (38%), 19q (32%), and 21q
      (37%). These results suggest that several putative tumor suppressor genes, in
      addition to the cyclin D and TP53 genes that are sometimes mutated in esophageal
      carcinomas, may be associated with development and/or progression of esophageal
      cancer. By a comparison of LOH on each chromosomal arm with clinicopathological
      parameters, we have found a significant correlation between LOH on 19q and
      regional lymph node metastases. Interestingly, the frequency of LOH on 17q was
      significantly higher in tumors in female patients (12 of 14 cases) than in those
      in male patients (20 of 56 cases) (P = 0.0009 by Fisher's exact test).
      Furthermore, we examined for mutations of the APC gene on chromosome arm 5q.
      Screening of nearly one third of the APC coding region, including the MCR
      (mutation cluster region), revealed no alterations. Therefore, although allelic
      loss at the APC locus is frequent in squamous cell carcinomas of the esophagus,
      it is likely that a gene on 5q other than APC is involved in esophageal
      tumorigenesis.

PMID- 7522039
TI  - t(1;19) without detectable E2A rearrangements in two t(14;18)-positive
      lymphoma/leukemia cases.
AB  - Translocation t(1;19)(q23;p13) plays a crucial role in the pathogenesis of
      childhood pre-B cell leukemia and results in the formation of a fusion gene E2A
      PBX1 that encodes a hybrid transcription factor with oncogenic potential. Here we
      describe two cases, one follicular lymphoma and one acute lymphoblastic
      leukemia/lymphoma, characterized by a complex karyotype including t(14;18),
      t(8;14), as well as t(1;19). Molecular studies in both cases failed to show
      rearrangements of the E2A gene. These results suggest that the t(1;19) found as a
      secondary chromosome change in t(14;18)-positive lymphoma/leukemia might be a
      molecular variant of the t(1;19) that is typical of childhood pre-B cell
      leukemia.

PMID- 7522042
TI  - Clonal karyotypic abnormalities in colorectal adenomas: clues to the early
      genetic events in the adenoma-carcinoma sequence.
AB  - Cytogenetic analysis of short-term cultures from colorectal adenomas revealed
      acquired clonal chromosome aberrations in 14 of 17 tumors. In 4 adenomas, only
      numerical changes were found, whereas 10 had structural rearrangements. Trisomy 7
      was found as the sole change in one of the tumors and together with other
      numerical changes in another. A +7 was also present in one case with structural
      aberrations. Other recurrent numerical aberrations were -14 and -18, both found
      in 2 adenomas with structural karyotypic changes; in addition, one chromosome 14
      was lost in one of the tumors with only numerical changes. The chromosome most
      often involved in structural aberrations was chromosome 1. In 6 cases, the
      rearrangements led to changes in 1p, always with loss of material. The
      breakpoints were at 1p32-36. One adenoma had deletion of 1p as the only change.
      Other chromosomes that were involved in changes in more than 2 cases were
      chromosomes 8, 13, and 17. These rearrangements typically led to gain of 8q and
      13q and loss of 17p. The adenomas with structural abnormalities were generally
      larger and had a higher degree of dysplasia than did the adenomas with numerical
      changes only or those with a normal karyotype. All adenomas with a tubulovillous
      or villous architecture had structural rearrangements. Our findings confirm that
      a subset of colorectal adenomas exists that have only numerical chromosome
      aberrations. They also support our previous conclusion that loss of material from
      distal 1p is an early event in colorectal tumorigenesis, but that other
      cytogenetic aberrations follow and typically are present already at the
      adenomatous stage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522041
TI  - Correlation of loss of heterozygosity at 11p with tumour progression and survival
      in non-small cell lung cancer.
AB  - Loss of heterozygosity (LOH) affecting loci at 11p13 and 11p15 occurs in
      childhood and adult carcinomas, including non-small cell lung cancer (NSCLC). In
      NSCLC, the highest reported frequency of LOH was 72% at the 11p13 catalase (CAT)
      locus. As this locus is centromeric to the Wilms' tumour (WT1) locus, possible
      involvement of WT1 in the pathogenesis of NSCLC was considered. We thus examined
      101 cases of NSCLC for LOH at the WT1 and five other polymorphic loci along 11p.
      At 11p13, the frequencies of LOH were 20% (9/46) at the FSHB locus, 9% (5/53) at
      the WT1 locus, and 15% (6/41) at the CAT locus. The shortest region of overlap
      (SRO) at 11p13 was mapped centromeric to, but excluding, the WT1 locus. Only
      adenocarcinomas showed LOH in this region. At 11p15, LOH affected 23% (18/77) of
      informative cases, with the highest frequency of 36% at the insulin (INS) locus.
      The SRO at 11p15 was mapped telomeric to the RRM1 locus. A third region, at 11p13
      15 between WT1 and RRM1, was also affected by LOH. LOH at 11p correlated
      significantly with advanced T stage and nodal involvement in NSCLC tumours. In
      the squamous cell carcinoma subtype, LOH along 11p also correlated with nodal
      involvement. Furthermore, squamous tumours with LOH involving 11p13 loci had
      significantly worse survival than those without LOH. These data suggest that
      tumor suppressor gene(s) on 11p affect the progression of NSCLC, particularly
      squamous cell carcinomas.

PMID- 7522043
TI  - Chromosome abnormalities in hairy cell leukaemia variant.
AB  - We describe chromosome abnormalities in 6 patients with hairy cell leukaemia
      (HCL) variant, a rare B-cell disorder with clinical and laboratory features
      intermediate between HCL and B-prolymphocytic leukaemia (B-PLL). All but one had
      marked splenomegaly and a raised white blood cell count (median 40 x 10(9)/l)
      with over 80% nucleolated hairy cells. These cells had a B-cell immunophenotype
      distinct from that of typical HCL. All patients but one are alive with stable
      disease with a median follow-up of 60 months. Numerical chromosome changes
      included loss of chromosomes 2, 3, 4, 6, 10, 19, 21, and X. three cases had
      translocations involving the immunoglobulin gene regions: t(14;17)(q32;q11),
      t(14;22)(q32;q11), and t(2;8)(p11.12;q24). Immunocytochemistry demonstrated the
      presence of the MYC protein in cells from the case with t(2;8) but not in two
      others. Other structural abnormalities included t(3;10)(q27;q22) and
      t(3;12)(q27;q13) in the same patient, der(17)t(7;10;17)(p11;q27;q22),
      t(1;3)(q25;p21), t(8;21)(p12;q11), t(17;21)(p11;p11), del(6)(q15), del(7)(q34),
      and del(14)(q24).

PMID- 7522044
TI  - Numerical chromosome changes in a nasal polyp.
AB  - The etiology of nasal polyposis is not fully understood. We found numerical
      chromosome changes in one out of five cytogenetically investigated nasal polyps.
      The histological picture of this case was characterized by the presence of
      histiocyte-like cells, which were absent in the remaining cytogenetically normal
      polyps.

PMID- 7522045
TI  - Complex karyotypic abnormalities in a primary carcinoma of the fallopian tube.
AB  - Short-term cultures from a primary carcinoma of the Fallopian tube, a tumor type
      not characterized before by chromosome banding, were examined cytogenetically.
      Complex chromosome aberrations were found in all mitoses, yielding the karyotype
      41,XX,del(1)(p34),del(2)(q31),i(8)(q10),-9, + dic(9;19)(p13;p13),
      der(12)t(9;12)(p13;q22),-13,-16,-17,-18,-19,-22, +r [61]/84-86,idemx2[15].
      Several of the aberrations in the present case are similar to changes found in
      adenocarcinomas of other organs, including carcinomas of the ovaries and uterus,
      indicating pathogenetic similarities between Fallopian tube malignancies and the
      more common gynecologic cancers.

PMID- 7522046
TI  - Cytogenetic study of angiosarcoma of the breast.
AB  - Angiosarcoma of the breast is quite rare, and the development of cutaneous
      angiosarcoma after segmental mastectomy and radiation therapy is even less
      common. A cytogenetic analysis of a mammary angiosarcoma arising in a breast
      after previous irradiation and segmental mastectomy for infiltrating ductal
      carcinoma revealed multiple clonal rearrangements involving chromosomes X, 1, 2,
      3, 4, 5, 6, 7, 8, 9, 15, 17, 20, and 22. No cytogenetically analyzed
      angiosarcomas of the breast have been reported before.

PMID- 7522047
TI  - Characterization of homogeneously staining regions in a small cell lung cancer
      cell line, using in situ hybridization with an MYCN probe.
AB  - The cell line CIPL38 was derived from the pleural effusion of a patient with
      small cell lung cancer. The karyotype was hyperdiploid and complex with a
      variable number of marker chromosomes. Two of the markers had large homogeneously
      staining regions (hsr), which were shown to consist of amplified MYCN by in situ
      hybridization. One hsr bearing a marker chromosome could not be identified with G
      banding, but the other was situated on a der(14). This was elucidated further
      with FISH analysis, which enabled the identification of sequences of chromosome i
      involved in a complex rearrangement with chromosome 14 and the hsr.

PMID- 7522048
TI  - Comparison of fibrovascular ingrowth into hydroxyapatite and porous polyethylene
      orbital implants.
AB  - Two porous orbital implants available for clinical use in the anophthalmic socket
      are hydroxyapatite (HA) and porous polyethylene (PP). We examined the rate and
      the extent of fibrovascular ingrowth into these implants using histopathologic
      criteria in a rabbit model. Thirty-two New Zealand white rabbits underwent a
      unilateral enucleation with placement of a 14-mm spherical orbital implant.
      Twelve rabbits received HA, 12 small-pore PP, and 8 large-pore PP. The implants
      inserted were wrapped either in autologous sclera with and without anterior
      fenestrations or as unwrapped spheres. The implants were harvested at 6 and 12
      weeks. The extent of fibrovascular ingrowth was assessed by determining the
      percentage of the cross-sectional area penetrated by fibrovascular tissue. On
      gross inspection, 12 implants (37.5%) were found to be exposed at harvesting;
      however, only two were grossly infected. The highest rate of exposure was found
      among the unwrapped implants. Wrapped versus unwrapped and fenestrated versus
      unfenestrated implants did not result in significant differences in the extent of
      vascularization. Hydroxyapatite implants were vascularized most rapidly. The
      small-pore PP implants did not become fully vascularized during the study, and
      yet complete vascularization was found in the large-pore PP at 12 weeks. The most
      intense areas of microscopic fibrovascular ingrowth were in the region where the
      extraocular muscles were in direct contact with the implant and at the posterior
      opening. Exposure of the implant was accompanied by chronic and acute
      inflammation. Both HA and large-pore PP spherical implants are capable of
      complete vascularization in this animal model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522049
TI  - Beta 2-integrin dependent aggregate formation between LB T cell lymphoma and
      spleen cells: assessment of correlation with spleen invasiveness.
AB  - LB is an aggressive T cell lymphoma which rapidly invades the spleen and lymph
      nodes of BALB/c mice after s.c. inoculation. We previously reported that mAb
      directed against the beta 2 chain of the leukocyte function-associated antigen-1
      (LFA-1) adhesion molecule (CD18) blocked the invasion of LB cells into the spleen
      but not into the lymph nodes. The same antibody also blocked in vitro aggregate
      formation between normal spleen cells and LB cells. However, aggregate formation
      between normal lymph node cells and LB cells was not detected, regardless of
      ratio. In an attempt to evaluate the association between aggregate formation and
      tumor invasion of the lymphoid organs, we have now extended the study.
      Intravenous injection of anti-CD18 mAb, which blocked spleen invasion by LB
      cells, also blocked the formation of ex vivo aggregates, spontaneously generated
      in spleen, but not in lymph node, cell suspensions of BALB/c mice s.c. inoculated
      with LB cells. In contrast, mAbs unable to block spleen invasion were ineffective
      inhibitors of both in vitro and ex vivo aggregate formation between spleen and LB
      cells. Spleens of nude mice that did not provide a supportive environment for
      lymphoma invasion, were also deficient in target cells forming aggregates with LB
      cells. In line with this observation, enriched T cells formed more aggregates
      with LB cells than did enriched non-T cells, indicating the lymphoma's
      preferential binding to splenic T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522050
TI  - Isotope-edited Fourier transform infrared spectroscopy studies of calmodulin's
      interaction with its target peptides.
AB  - The ubiquitous calcium-binding protein calmodulin (CaM) regulates a wide variety
      of cellular events by binding to and activating many distinct target enzymes. The
      CaM-binding domains of most of these enzymes are contained in a contiguous
      stretch of amino acids with a length of approximately 20 residues. In this work,
      we have used "isotope-edited" Fourier transform infrared spectroscopy to study
      the interaction of CaM with synthetic peptides resembling the CaM-binding domains
      of myosin light chain kinase (MLCK), constitutive nitric oxide synthase (cNOS),
      and caldesmon (CaD). Uniform labeling of CaM with carbon-13 causes the amide I
      band of the protein to shift approximately 55 cm-1 to lower frequency in D2O,
      leaving a clear window in the infrared spectrum for observing the amide I band of
      the unlabeled target peptides. Upon complex formation, the amide I bands of the
      CaM-binding domains of MLCK and cNOS shift 4 cm-1 toward higher frequency (to
      approximately 1648 cm-1), and have a narrower bandwidth compared to the peptide
      in aqueous solution. These spectral changes and the fact that the infrared
      spectra of these two peptides in their complex with CaM closely resemble those
      recorded in a mixture of D2O and the helix inducing solvent trifluoroethanol
      indicate that they bind to CaM in an alpha-helical conformation. The CaM-binding
      domain of CaD also showed similar, but less dramatic, spectral changes; this is
      in agreement with the fact that it binds to CaM with lower affinity and a shorter
      alpha-helix.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522052
TI  - An RNA binding site in a tRNA synthetase with a reduced set of amino acids.
AB  - A 30 amino acid helix-loop of known structure on the surface of the C-terminal
      domain of the class I Escherichia coli methionine tRNA synthetase is essential
      for methionine tRNA anticodon discrimination. Replacing this 30 amino acid
      peptide with a previously described sequence containing residues from the wild
      type protein imbedded in a sequence matrix of mostly alanines and serines, we
      used a combinatorial mutagenesis and selection strategy to define residual wild
      type residues that are not replaceable with alanine or serine, because they are
      needed for specific recognition of methionine tRNA. Four were identified, of
      which three have functional side chains (Asn, Arg, Lys). These four and a fifth
      (Trp) that was previously identified are located at the end of the helix and
      within the loop, lie on the same side of the structure, and span a distance of
      about 20 A. We conclude that, within the alanine, serine sequence matrix, only a
      few non-alanine, non-serine residues in the specificity-determining part of the
      structure are essential.

PMID- 7522051
TI  - Diminished heparin binding of a basic fibroblast growth factor mutant is
      associated with reduced receptor binding, mitogenesis, plasminogen activator
      induction, and in vitro angiogenesis.
AB  - Using modeling of heparin-fibroblast growth factor interactions, we replaced four
      basic residues of basic fibroblast growth factor (FGF-2) with neutral glutamine
      residues by site-specific mutagenesis to give the mutants K128Q, K138Q, K128Q
      K138Q, R129Q, K134Q, and R129Q-K134Q. The FGF mutants were characterized for
      their receptor and heparin binding affinities, mitogenic and cell proliferation
      activities, and their ability to induce plasminogen activator (PA) production and
      in vitro angiogenesis by cultured endothelial cells. Heparin binding properties
      and biological activities of the three mutants involving R129 and K134 remained
      essentially unchanged; however, significant changes for three mutants involving
      K128 and K138 were found. The KD values for heparin binding for K128Q and K138Q
      mutants were increased about 10-fold, and that for the K128Q-K138Q double mutant
      was increased by about 100-fold. The mutant K128Q-K138Q required a 10-fold higher
      concentration of heparin to promote binding to heparan sulfate proteoglycan
      (HSPG)-deficient CHO cells transfected with fibroblast growth factor receptor-1
      (FGFR1) or to induce DNA synthesis in HSPG-deficient myeloid cells transfected
      with FGFR1. Binding affinities of the mutants to cell surface receptors on BHK-21
      cells, however, were similar to that of wild-type FGF-2. In endothelial cell
      proliferation assays the activities of K128Q and K128Q-K138Q were about 10-fold
      lower than that of the wild-type protein, whereas the K138Q mutant exhibited wild
      type activity. In addition, the K128Q-K138Q mutant displayed a markedly lowered
      capacity to induce PA activity in cultured endothelial cells and to form
      capillary-like structures in an in vitro angiogenesis model.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7522053
TI  - Identification of a PAI-1 binding site in vitronectin.
AB  - Active PAI-1 (plasminogen activator inhibitor 1) is bound to vitronectin in
      plasma and in the extracellular matrix. In this study we aimed at identifying the
      PAI-1 binding site in vitronectin, which at present is a matter of dispute.
      Vitronectin was cleaved with trypsin and the fragments were tested for inhibitory
      effect on the PAI-1/vitronectin interaction using vitronectin-coated microtiter
      plates. Intact vitronectin and the tryptic digest of vitronectin both caused a
      50% reduction in PAI-1 binding at a concentration of about 2 nmol/I. Gel
      filtration on Sephadex G-50 superfine of the tryptic peptides resulted in one
      main peak of inhibitory activity. The elution volume, Kav, was 0.55 indicating
      (a) medium-size peptide(s). The peptide was further purified by reverse-phase
      HPLC. Structural analysis revealed that it constituted the 45 NH2-terminal amino
      acid residues in vitronectin. The NH2-terminal vitronectin peptide caused a 50%
      decrease in PAI-1 binding to the vitronectin-coated microtiter plates at a
      concentration of about 13 nmol/l. Thus, the peptide is a little less effective in
      this respect than intact vitronectin. Reduced and S-carboxymethylated peptide had
      no effect on the interaction. The NH2-terminal vitronectin fragment increased the
      stability of active PAI-1 by about 60%, which is a little less than with intact
      vitronectin. The peptide also prevented PAI-1 from oxidation with chloramine T.
      The half-life was prolonged about 4-fold as compared to about 30-fold with intact
      vitronectin.

PMID- 7522055
TI  - Characterisation and expression of a maize U3 snRNA gene.
AB  - We have used a probe encoding a U3snRNA gene of Arabidopsis to isolate maize
      U3snRNA genomic sequences. Of two clones sequenced, one encodes a single U3 gene
      which has been shown to be expressed in transfected maize protoplasts. The second
      clone encodes a U3 related sequence which appears to be an RNA-mediated
      pseudogene.

PMID- 7522056
TI  - The integrin alpha v gene: identification and characterization of the promoter
      region.
AB  - We isolated a 15.5 kilobase pair DNA fragment that contains the 5' end of the
      human vitronectin receptor alpha subunit (alpha v) gene. The nucleotide sequence
      of the 5' flanking region, first exon and part of the first intron of the alpha v
      gene was determined. The sequence showed that the 5' end of the alpha v gene lies
      within a CpG island. The transcriptional initiation site was mapped 169 base
      pairs upstream of the alpha v translational initiation site. The 5' flanking
      region of the alpha v gene does not contain TATA or InR transcriptional control
      elements but does contain four Sp1 binding sites, two Ets binding sites and one
      GATA binding site. The identified alpha v gene 5' flanking region directed the
      expression of human growth hormone in transfected HeLa cells. Successive
      deletions of the 5' flanking region demonstrated a 222 bp region that exerts a
      strong positive effect on alpha v promoter activity.

PMID- 7522054
TI  - Inducible nitric oxide synthase from human articular chondrocytes: cDNA cloning
      and analysis of mRNA expression.
AB  - Human articular chondrocytes can be induced by IL-1 beta, TNF-alpha or LPS to
      release high levels of nitric oxide. Using degenerate PCR primers based on
      homologous regions from previously cloned NOS enzymes, a 1.9 kb cDNA fragment was
      amplified from IL-1 beta stimulated but not from resting chondrocytes. Screening
      of a lambda gt11 cDNA library, which was prepared from RNA of IL-1 beta activated
      chondrocytes, resulted in the isolation of the complete cDNA, encoding a protein
      of 1153 amino acids. Comparison of the cDNA sequence identified human chondrocyte
      iNOS to be almost identical to the sequence recently reported for the hepatocyte
      enzyme, differing in 12 amino acids. Northern blot analysis revealed, that
      stimulated chondrocytes express a single 4.5 kb iNOS mRNA species. IL-1 beta
      induction of iNOS mRNA was detectable by 6 h and continued to be elevated
      throughout a 72 h culture period. Screening of a human bone cDNA library
      identified this inducible NOS to be also expressed by bone cells.

PMID- 7522057
TI  - Successful treatment of neutropenia in T-LGL leukemia (T gamma-lymphocytosis)
      with granulocyte colony-stimulating factor.
AB  - Severe neutropenia is a common feature in patients with T-large granular
      lymphocytic (LGL) leukemia. Neutropenia often causes severe infections and
      septicemia, thus representing a major cause of morbidity and mortality in this
      disease. We have treated two outpatients with T-LGL leukemia who had severe
      neutropenia (neutrophils < 0.2 x 10(9)/l) successfully with G-CSF (5
      micrograms/kg daily, s.c.). After 10 days of treatment the neutrophil count was
      within the normal range and a severe oral infection healed rapidly. We conclude
      that G-CSF therapy is able to normalize the neutrophil count in T-LGL leukemia
      within a few days and that it can be used to treat severe infections in these
      patients even on an outpatient basis.

PMID- 7522058
TI  - Successful treatment of chronic wound infection in neutropenia and rheumatoid
      arthritis with filgrastim (rhG-GSF)
AB  - A 73-year-old woman was diagnosed with seropositive destructive rheumatoid
      arthritis in 1981. She was treated with cortisone, chloroquine, and
      cyclophosphamide (Sendoxan) in 1982 and 1984 and contracted severe neutropenia.
      After that she only received cortisone. During 1991, again low neutrophilic
      counts were registered, especially granulocytopenia. At first, B-cell lymphoma
      was suspected, but later Felty's syndrome was established. The patient was
      treated with high-dose cortisone with some success and had a few minor septic
      episodes. In May 1992 she contracted a traumatic wound on the back of the lower
      leg. Conservative treatment resulted in a worsening of the condition and an
      increased wound area, most likely related to the neutropenic condition. In mid
      July the patient was hospitalized. Bacterial isolates yielded mixed gram-negative
      enteric bacteria from the wound. Parenteral antibiotic treatment was started,
      followed by oral drugs, rhG-CSF (filgrastim) was given subcutaneously once a day,
      starting 3 days after admission. This resulted in increased numbers of peripheral
      granulocytes. The ulcer started to heal and by mid August the patient received a
      transplant with autologous skin grafting. In mid September the wound was
      completely healed. It is concluded that the combination of antibiotics, skin
      transplantation, and G-CSF was necessary for the successful result. Actually, the
      bacterial growth did not call for antibiotics, but it was considered necessary to
      cover for staphylococci. No worsening of the underlying arthritis was observed.

PMID- 7522059
TI  - The analytical performance of the Ciba Corning ACS:180 automated immunoassay
      system. A multicentre evaluation.
AB  - The analytical performance of the Ciba Corning ACS:180 automated immunoassay
      system was studied according to a revised version of the ECCLS guidelines and
      partly according to a protocol of the Societe Francaise de Biologie Clinique
      (SFBC) in a multicentre evaluation involving three laboratories. The
      determination of 8 analytes yielded more than 50,000 data. The values for
      imprecision showed that the ACS:180 is comparable to the ES-600, and gives better
      results for many analytes than other comparison methods. The recovery of system
      assigned values in control sera was acceptable for all analytes. The upper limits
      of linearity claimed by the manufacturer were confirmed for all analytes. In many
      cases, the results for patients' samples showed good agreement between the
      ACS:180 and several different comparison methods. One exception was lutropin,
      with a large spread of the data. Furthermore, for human chorionic gonadotropin
      and prostate-specific antigen, the slopes of the fitting lines were significantly
      higher than 1. Triacylglycerols and haemoglobin did not significantly influence
      the measurements of any analyte. Bilirubin affected the measurement of
      triiodothyronine and human chorionic gonadotropin. Significant drift or carry
      over effects were not detected. The selective ACS:180 is fully automatic,
      requires relative short personnel time, and was easy to operate.

PMID- 7522060
TI  - Detection of culture-resistant bacterial pathogens by amplification and
      sequencing of ribosomal DNA.
AB  - Molecular phylogeny is profoundly influencing the field of bacterial evolution.
      New knowledge in this area has led to an exciting ability to detect and classify
      bacteria without culturing them. The process involved consists of either
      amplification or cloning of ribosomal DNA from a bacterial population, sequencing
      of this ribosomal DNA, and phylogenetic analysis of the sequences obtained. This
      approach has so far been applied successfully to four infectious diseases:
      bacillary angiomatosis, human ehrlichiosis, Whipple's disease, and Tyzzer's
      disease. Interpretation of data obtained by this method has been straightforward.

PMID- 7522061
TI  - (S)-linalyl, 2-phenylethyl, and benzyl disaccharide glycosides isolated as aroma
      precursors from oolong tea leaves.
AB  - Three glycosides, 6-O-beta-D-xylopyranosyl-beta-D-glucopyranosides (beta
      primeverosides) of the aroma constituents, linalool, 2-phenylethanol, and benzyl
      alcohol, were isolated as aroma precursors from the tea leaves (Camellia sinensis
      var. sinensis cv. Shuixian and Maoxie, cultivars for oolong tea). The isolation
      was guided by acid or enzymatic hydrolysis, and subsequent GC and GC-MS analyses.
      The linalyl glycoside is the first example of naturally occurring (S)-linalyl
      beta-primeveroside.

PMID- 7522063
TI  - Effects of chlordecone on the gonads of freshwater catfish, Heteropneustes
      fossilis.

PMID- 7522062
TI  - Psychosocial and psychomotoric development of very low birthweight infants with
      necrotizing enterocolitis.
AB  - Twenty-six very low birthweight infants (VLBI) were treated for necrotizing
      enterocolitis (NEC). We investigated their consecutive health problems and
      psychosocial development. METHOD: One to 13 years after onset of NEC, follow-up
      studies were performed in 12 of the surviving children. Identical follow-up
      studies were performed in 6 VLBI who had been operated on for diseases other than
      NEC (control group). We used a detailed interview, a Denver test and a drawing
      test. RESULTS: Five children of the NEC group had major persistent health
      problems that impaired their psychomotoric and psychosocial development
      (including hearing impairment, concomitant strabismus, early onset bronchial
      asthma). Nine of 12 VLBI of the NEC group showed signs of reduced social contact,
      logopaedic problems and minimal partial skill reductions. CONCLUSION: We found
      similar results in both children who suffered from NEC and in a small control
      group of VLBI who had not suffered from NEC, therefore impaired psychomotoric and
      psychosocial development is probably due to prematurity.

PMID- 7522064
TI  - [Effect of hemodilution on retinal hemodynamics in retinal branch vein
      occlusion].
AB  - The aim of hemodilution therapy in branch retinal vein occlusion is to lower the
      hematocrit (HCT) and plasma viscosity and thus to ameliorate perfusion of the
      affected areas. In this study we compared the influence of hemodilution therapy
      on the retinal hemodynamics of affected areas with unaffected areas. Thirty
      patients with branch vein occlusion (duration of symptoms less than 14 days) aged
      40-84 years (mean 63 +/- 11 years) were examined. All patients received iso- (HCT
      > or = 42%) or hypervolemic (HCT < 42%) hemodilution with hydroxyethyl-starch (MW
      200,000/0.5 10%, HAES-steril) for 10 days. Retinal hemodynamics were quantified
      by means of video fluorescein angiography assessing arteriovenous passage time
      (AVP) of the affected and unaffected branches. Hemodilution resulted in a
      significant decrease in hematocrit, plasma viscosity and erythrocyte aggregation.
      The arteriovenous passage time of the affected area improved significantly
      (before therapy 4.91 +/- 2.2 s, after therapy 3.9 +/- 1.6 s). The unaffected
      branch showed no significant change in the arteriovenous passage time (1.85 +/-
      0.7 s before and 1.79 +/- 0.7 s after therapy). The decrease in AVP in the
      affected branch indicates ameliorated perfusion in the affected branch area
      without changing the retinal hemodynamics in unaffected areas.

PMID- 7522065
TI  - [Ischemic or non-ischemic central artery occlusion. An explanation for the
      development or lack of development of neovascularization].
AB  - In a retrospective study we analyzed 29 central retinal artery occlusions (CRAO)
      with reference to the findings of ophthalmodynamometry (ODM) and fluorescein
      angiograms (FLA). We tried to find explanations for the relatively low rate of
      neovascularization in CRAO and predictive constellations for CRAO that will
      develop neovascularization. In 5 eyes the pathologic findings were classed as
      ischemic ophthalmopathy because of carotid or ophthalmic artery stenosis: 2 of
      these 5 eyes showed iris neovascularization (rubeosis iridis), while the other 3
      "only" showed a CRAO with no clinical signs of ischemic ophthalmopathy. Of the
      remaining 24 eyes with CRAO there were 2 eyes with rubeosis iridis, which could
      be attributed to the CRAO itself (8.3%). FLA revealed ischemic perfusion of the
      retina in these 2 cases. ODM revealed reperfusion of the central artery (CRA) in
      17 of 25 eyes with CRAO (71%) within the first 2 weeks. In 2 blind eyes that were
      re-examined 3 and 5 months after CRAO no iris or retinal neovascularization was
      found despite persisting malperfusion of CRA. In these 2 cases the minimal
      retinal perfusion needed because of complete retinal necrosis was sufficient
      explanation for the nonevolution of neovascularization. If ischemia is the
      essential condition for neovascularization, we can propose two explanations for
      non-development of neovascularization after CRAO: either there is adequate
      recanalization (majority of cases) or the need for perfusion is minimal or zero.
      Only in cases of persisting malperfusion and partially surviving retinal tissue
      (function!) will neovascularization perhaps develop. ODM is an adequate method of
      estimating the perfusion of CRA.

PMID- 7522066
TI  - Enormous hemangiosarcoma of the heart.
AB  - This report describes a 26-year-old patient with hemangiosarcoma of the heart and
      summarizes the clinicopathological features in previous reports of patients with
      cardiac angiosarcoma. The patient was admitted to our hospital because of a
      syncope and one episode of nocturnal dyspnea and hemoptysis. In his history he
      complained of progressive weakness and loss of weight over the past 2 months.
      Echocardiography and computed tomography of the chest showed inhomogeneous masses
      in the pericardial cavity completely surrounding the heart and involving the
      ascending aorta and the superior vena cava. Histological examination of the
      tissue obtained from the mass by fine needle technique revealed a poorly
      differentiated malignant tumor of mesenchymal origin. Exploratory thoracotomy
      followed by tumor biopsies showed an inoperable cardiac hemangiosarcoma of
      enormous size with multiple metastases in both lungs. Palliative tumor resection
      was not performed. During the postoperative course the patient still required
      controlled ventilation. After 3 days of cytostatic chemotherapy no regression of
      tumor mass was seen by chest radiography. Cardiorespiratory insufficiency was
      progressive, and the patient died within 3 weeks after admission.

PMID- 7522067
TI  - An alpha-fetoprotein producing pancreatic cystadenocarcinoma.
AB  - An autopsy case of an 83-year-old Japanese woman with pancreatic cancer with
      significantly elevated serum alpha-fetoprotein levels is reported. The pancreatic
      tumor was a mucinous cystadenocarcinoma with multiple metastasis to the liver.
      The immunohistochemistry for alpha-fetoprotein revealed positive reactivity in
      the cytoplasm of cancer cells in the primary and liver metastatic lesions. The
      current case is the first reported in which mucinous cystadenocarcinoma of the
      pancreas produced alpha-fetoprotein.

PMID- 7522068
TI  - Agranulocytosis induced by antithyroid therapy: effects of treatment with
      granulocyte colony stimulating factor.
AB  - A 26-year-old woman was admitted to hospital with high fever, severe tonsillitis,
      and gastroenteritis. Because of Graves' disease she had been treated with
      methimazole for 18 months. Leukopenia and agranulocytosis in combination with a
      typical bone marrow, exhibiting a complete arrest of myelopoiesis at the stage of
      promyelocytes led to the diagnosis of an antithyroid therapy induced
      agranulocytosis. After 1 week of antibiotic treatment without changes in
      neutrophil counts, granulocyte colony stimulating factor treatment at a dose of
      300 micrograms/day subcutaneously was started. Twenty-four hours after the first
      administration the neutrophil counts began to rise, to 4389/microliters, with a
      maximum after the third administration and stabilizing at normal levels within 10
      days. Since agranulocytosis is considered to be a severe and fatal complication
      of methimazole therapy, treatment with granulocyte colony stimulating factor
      seems to be useful for this life-threatening condition.

PMID- 7522070
TI  - Modulation of immunological histamine release from human lung fragments by stem
      cell factor, IL-3, IL-5 and GM-CSF: comparison with human leukocytes.
AB  - Because of the importance of cytokines in the regulation of allergic
      inflammation, we investigated the effects of SCF, IL-3, IL-5 and GM-CSF on
      immunological histamine release from sensitized human lung fragments as well as
      human leukocytes. SCF (0.2-20 ng/ml) caused a concentration-related enhancement
      of anti-IgE (1/100) induced histamine release from lung fragments reaching
      maximally 64% at 20 ng/ml. In contrast, enhancement produced by IL-5, IL-3 and GM
      CSF (0.2-20 ng/ml) was quite marginal and reached at best around 20% at the
      higher concentration, IL-5 being slightly more effective than IL-3 and GM-CSF.
      Further, SCF potentiated histamine release whatever the level of immunological
      control whereas potentiation by IL-5 primarily occurred when the amount of
      histamine release induced by the immunological control ranged between 5 and 10%.
      SCF acted synergistically with IL-5, producing a greater enhancement of histamine
      release than the sum of each cytokine used alone. Both SCF and, to a lesser
      extent, IL-5 potentiated anti-IgE-mediated histamine release regardless of
      passive sensitization of lung fragments. Unlike what was observed with lung
      fragments, IL-3, GM-CSF and to a lesser extent IL-5, were potent enhancing agents
      of anti-IgE (1/2,000)-induced histamine release from leukocytes. Maximal
      enhancement produced by IL-3 (20 ng/ml), GM-CSF (2 ng/ml) and IL-5 (20 ng/ml)
      reached 92%, 78% and 61%, respectively. By contrast, SCF (0.2-20 ng/ml) was
      ineffective on human leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522072
TI  - The balance between lymphatic and systemic absorption determines the outcome of
      sensitization for anaphylaxis in rats.
AB  - Rats were sensitized to chicken ovalbumin or human gamma-globulin by inoculation
      without adjuvants into the peritoneal cavity in the healing phase of a chemical
      peritonitis. This phase is associated with striking enhancement of lymphatic
      absorption. Small doses of antigen sensitized the rats for subsequent induction
      of anaphylaxis, but large doses were almost completely ineffective (inverse dose
      response relation). When certain adjuvants were added to the antigen, both high
      and low doses of antigen were effective sensitizers for anaphylaxis. Neither high
      nor low doses of antigen sensitized if injected without adjuvants into the
      unprepared peritoneal cavity or by any other route. The effects of sensitization
      with low or high doses of antigen and the results of inoculation by effective and
      ineffective routes were interpreted in terms of the balance between absorption
      into the lymphatics and into the systemic blood circulation. Supplemental antigen
      inoculated into the systemic circulation was able to tip the balance against
      sensitization even when sensitization was done with potent adjuvants and by a
      favorable route. Splenectomy had little or no effect on suppression by
      supplemental antigen.

PMID- 7522071
TI  - In vivo biological activity of recombinant Der p II allergen of house-dust mite.
AB  - The cDNA coding for one of the major allergens of Dermatophagoides pteronyssinus,
      Der p II, has been cloned and expressed in Escherichia coli as a fusion protein
      with glutathione S-transferase. The recombinant material (r Der p II) was tested
      in the skin of house-dust allergic patients, and was found to be almost as active
      as the purified native allergen (n Der p II) in stimulating immediate
      hypersensitivity reactions. The positivity to r Der p II in these patients, who
      were selected for their skin-test reactivity to house-dust extract (HDE) and
      whole mite extract (WME), was over 60%, and 80% of their sera contained
      detectable IgE antibody against the recombinant allergen. The level of specific
      IgE antibody against r Der p II was a mean of 40% of that against WME in the sera
      of patients who were skin test positive to both allergen preparations. In
      contrast to the house-dust allergic patients, none of a group of allergic
      patients whose clinical history did not implicate house dust, and who were skin
      test negative to HDE or WME, were positive to r Der p II. Of interest was the
      observation that only 37% of a group of subjects who were skin test positive to
      HDE and WME, but who reported no clinical history of allergic disease upon
      natural exposure to house dust, reacted to r Der p II. These results demonstrate
      the biological activity of r Der p II, and indicate, in persons skin test
      positive to house-dust mite extract, an association between reactivity to Der p
      II and the manifestation of clinical symptoms.

PMID- 7522073
TI  - Effects of ovariectomy and estrogen on the serum levels of insulin-like growth
      factor-I and insulin-like growth factor binding protein-3.
AB  - To determine the effects of ovariectomy and 17 beta-estradiol (E2) on serum IGF-I
      and its binding proteins, female Sprague-Dawley rats, aged 95 days, were divided
      into four groups. Group 1 was sham-operated; groups 2, 3, and 4 were
      ovariectomized. Groups 3 and 4 received daily injections of 200 ng (low dose) and
      5000 ng (high dose) E2/kg body wt./day, respectively and the others were given
      solvent vehicle. Ovariectomy resulted in a significant increase in serum IGF-I (P
      < 0.001) at 30 and 35 days post-surgery; the increase was prevented in animals
      that received low-dose E2 while high-dose E2 reduced serum IGF-I levels below
      those of the sham-operated controls (P < 0.01). Serum IGF-binding proteins
      (IGFBPs) were determined by IGF-ligand blot analysis, and the resulting
      autoradiograms quantified by laser densitometry. The intensity of the IGFBP-3
      bands changed in parallel with serum IGF-I levels. Ovariectomy increased, low
      dose E2 restored, and high-dose E2 reduced serum IGFBP-3 levels compared to the
      levels for the sham-operated controls. The intensities of binding protein bands
      smaller than those of IGFBP-3 appeared unchanged by the treatment regimens. A
      Western immunoblot analysis with IGFBP-3 antiserum confirmed the ligand-blot
      data. The changes in the levels of IGF-I and its binding proteins were
      accompanied by ovariectomy-induced increase in osteoblast and osteoclast numbers
      and loss of cancellous bone that were attenuated by E2 administration. We
      conclude that there is a possible role for IGF-I in the pathogenesis of the
      increased bone turnover that occurs early in ovarian hormone deficiency.

PMID- 7522076
TI  - Random-coil model for glomerular sieving of dextran.
AB  - Dextran has been the most commonly employed test molecule for probing the
      selectivity of glomerular filtration to macromolecules of varying size. The usual
      theories for hindered transport of solid spheres through pores have limited
      utility in interpreting clearance data for dextran or other linear polymers
      because such polymers in solution more closely resemble random, solvent-filled
      coils than solid spheres. To provide a model for glomerular filtration of random
      coil macromolecules, the equilibrium partitioning of random coils between
      cylindrical pores and bulk solution was simulated using Monte Carlo calculations,
      and those results were combined with a hydrodynamic theory for restricted motion
      of solvent-filled polymer coils in pores. The rates of transport predicted for
      either neutral random coils or for solid spores of the same Stokes-Einstein
      radius were significantly lower than observed transport rates of dextran through
      the glomerular capillary wall or across synthetic porous membranes. This
      facilitation of dextran transport was modeled by postulating weak, attractive
      interactions between dextran monomers and the pore wall. The random-coil model
      with attractive interactions, modeled using a short-range, square-well potential,
      was found to adequately represent dextran sieving data in normal rats. Various
      limitations of this approach are discussed.

PMID- 7522078
TI  - Modulation of baroreceptor activity by ionic and paracrine mechanisms: an
      overview.
AB  - 1. The primary mechanism of activation of baroreceptors is mechanical deformation
      during vascular stretch. In addition, baroreceptor activity is modulated by ionic
      mechanisms and by neurohumoral and paracrine factors that act directly on the
      nerve endings. 2. Ionic mechanisms play a major role in causing baroreceptor
      activity to decline during a sustained increase in arterial pressure (adaptation)
      and in the suppression of activity that occurs after pressure returns to basal
      levels (post-excitatory depression). Activation of a 4-aminopyridine-sensitive K+
      channel contributes to adaptation, whereas activation of an electrogenic sodium
      pump is responsible for post-excitatory depression. 3. Factors released from
      vascular endothelium exert powerful effects on baroreceptor sensitivity.
      Prostacyclin increases baroreceptor sensitivity and contributes to baroreceptor
      activation during vascular stretch. Nitric oxide, endothelin and oxygen-derived
      free radicals suppress baroreceptor activity particularly at high levels of
      arterial pressure. The sympathetic neurotransmitter norepinephrine modulates
      baroreceptor activity: a) indirectly through its vasoconstrictor action, b)
      directly by binding to alpha-adrenergic receptors on the nerve endings, and
      c)through release of a cyclooxygenase metabolite, possibly prostacyclin, from
      endothelium. 4. Endothelial dysfunction contributes to baroreceptor impairment in
      atherosclerosis and in chronic hypertension. Loss of the excitatory influence of
      prostacyclin and increased formation of free radicals and possibly endothelin
      contribute to the baroreceptor dysfunction. Platelets aggregating at sites of
      endothelial damage in the carotid sinus release a stable diffusible factor that
      impairs baroreceptor sensitivity. 5. Therapeutic interventions may alter
      baroreceptor sensitivity through paracrine mechanisms. Treatment of hypertension
      or atherosclerosis may improve baroreceptor sensitivity by restoring endothelial
      function. Antiplatelet agents may enhance baroreceptor sensitivity.
      Antidepressant agents may decrease baroreceptor sensitivity by inhibiting
      prostacyclin and/or stimulating nitric oxide formation, which may contribute to
      dysregulation of the circulation in patients treated for depression.

PMID- 7522075
TI  - Electron microscopy of macromolecules. The French contribution.

PMID- 7522080
TI  - Tuberculosis in the world: the pattern of the new epidemic.

PMID- 7522079
TI  - [Post-transfusional hepatitis due to hepatitis virus C].
AB  - Cloned even before observed, C virus hepatitis seems to live out its natural life
      backwards. The C virus has begun to confide a part of its secrets to molecular
      Biology. Today's scientific data demonstrate that, for the most part, occurrences
      of post-transfusional hepatitis (PTH), which are neither A nor B, are the C
      virus. In order to lower the risk of blood transmission of the C virus, a
      systematic screening of HCV antibodies has been mandatory in Belgium since 1 July
      1991. Epidemiological data has testified that seroprevalence among blood donors
      is around 0.55%. Even though screening is an efficient measure to eliminate blood
      units that are suspected to be contaminated, implementing molecular Biology
      techniques (PCR or chain polymerization reaction) extracts detection of the viral
      genome, independent of the presence or absence of specific antibodies. The
      measurement of ALT (alanine amino transferase) as a surrogate marker in all blood
      units is not yet mandatory even though it has been described as a practical and
      low cost means to reduce PTH in blood recipients. Among the human measures
      available to determine the selection of blood donors are pre-donation anamnesis
      and awareness programmes to inform potential donors of risk factors. Post
      transfusional hepatitis C is a public health concern. The residual risk of
      contamination by blood products remains too great. Both human and serological
      measures have to be improved.

PMID- 7522074
TI  - Screening for ovarian, prostatic, and testicular cancers.
AB  - Screening for cancer should not be offered routinely to a symptomatic people on a
      population basis unless it has been shown to be effective in reducing mortality
      in randomised controlled trials. A suitable screening test should have high
      sensitivity and specificity and a high positive predictive value. There is an
      ethical imperative to ensure that the benefit to each person from screening is
      likely to outweight the possible harm. Preliminary studies have identified
      suitable screening tests for ovarian cancer, and a randomised controlled trail is
      about to start. There is considerable controversy about whether to screen for
      prostatic cancer. Likewise, there is uncertainty about the best means of treating
      localised prostatic cancer. Screening for prostatic cancer raises important
      ethical considerations which should not be ignored. Testicular self examination
      is of unproved benefit. Although there is a need for education about the early
      signs and symptoms of testicular cancer to reduce delay at presentation, a case
      cannot be made for screening.

PMID- 7522069
TI  - Inhibitory effect of the H1 antagonist loratadine on histamine release from human
      basophils.
AB  - Loratadine is a powerful H1 antagonist commonly employed in the treatment of
      allergic disorders. The present study was performed to investigate whether
      loratadine, in addition to anti-H1 activity, is able to modulate histamine
      release from human basophils. Leukocyte suspensions were prepared by dextran
      sedimentation of peripheral venous blood drawn from 10 normal subjects.
      Leukocytes were stimulated with anti-IgE (1/5,000), N-formyl-methionyl-leucyl
      phenylalanine (FMLP; 10 microM) and the Ca2+ ionophore A23187 (1 microM), and
      histamine release in the cell supernatants was measured by an automated
      fluorometric method. Loratadine, at concentrations ranging from 1 to 50 microM,
      exerted a dose-dependent inhibitory effect on IgE-mediated and IgE-independent
      histamine release. The concentrations inhibiting 50% of histamine release were 30
      microM (anti-IgE), 29 microM (FMLP) and 24 microM (Ca2+ ionophore A23187). The
      inhibitory activity of loratadine was optimal after incubation for 2 h at 37
      degrees C and the effect of the drug was no longer evident when leukocytes were
      stimulated 2 h after cell washing. Increased extracellular Ca2+ concentrations
      reduced the inhibitory activity of loratadine, indicating that external Ca2+ and
      loratadine have antagonistic effects on basophil histamine release. These results
      indicate that loratadine, in addition to H1 receptor blocking activity, has the
      capacity to inhibit histamine release from human basophils.

PMID- 7522077
TI  - A kinetic model of rat proximal tubule transport--load-dependent bicarbonate
      reabsorption along the tubule.
AB  - A model is presented of solute and water reabsorption along the proximal tubule
      of the rat kidney based on kinetic descriptions of the main membrane transport
      systems, in order to assess the extent to which these kinetics suffice to explain
      certain aspects of the global transport behaviour in this segment, especially
      with respect to bicarbonate reabsorption. The model includes in the apical
      membrane, an active proton pump, Na+/H+ antiport, Na-coupled transport of organic
      solutes, Cl-/formate exchange with formic acid recycling, and membrane
      conductances to protons and K+. In the baso-lateral membrane, besides the Na+/K+
      pump, the model includes Na(+)-3HCO3- and electroneutral K(+)-Cl- cotransporters,
      and membrane conductances for K+, H+, and, optionally, for Cl-. Appropriate
      passive diffusional pathways were included in both cell membranes and in the
      paracellular pathway. Using mass balance and electroneutrality constraints, these
      transport systems were built into an epithelial model which was then integrated
      (by finite difference approximation) into a model of a longitudinal tubule.
      Simulated cellular solute concentrations and luminal concentration profiles were
      in good agreement with reported experimental observations. We show that, given
      the reported transport kinetics for the Na+/H+ antiporter, a hitherto unexplained
      observation concerning load-dependent bicarbonate reabsorption can be shown
      mainly to result from the nonlinear longitudinal concentration profile for
      bicarbonate and pH. We also discuss problems of transcellular Cl- transport in
      the light of recent reports of basolateral Cl- conductance and observations
      relevant to apical Cl-/formate (or other base) exchange.

PMID- 7522081
TI  - Molecular biologic investigations of proto-oncogenes and growth factors in human
      testicular tumors.
AB  - Molecular genetic alterations of known protoncogenes and growth factors, e.g. c
      kit and its ligand SCF as well as hst1 and c-myc, are likely to play a role in
      the development of testicular cancer. In addition, identification and analysis of
      genes located on the frequently altered chromosome 12 represent an important
      focus of research. Genetic alterations may occur in a stepwise fashion, as
      described in other human tumors, leading to the development of the various
      histologic subtypes of testicular germ cell tumors. The characterization of these
      alterations are most likely to extend the traditional histopathologic tumor
      classifications.

PMID- 7522083
TI  - Characterization of a high molecular weight antigen of Cryptosporidium parvum
      micronemes possessing epitopes that are cross-reactive with all parasitic life
      cycle stages.
AB  - Crossreacting antigens between life cycle stages of Cryptosporidium parvum
      (Protozoa, Apicomplexa) were detected using monoclonal antibodies (mAbs). Shared
      epitopes were demonstrated by immunoelectron microscopy, at the level of
      micronemes of the sporozoite and merozoite stages; some dense granules were also
      labelled but not so intensively. The parasitophorous vacuole membranes of all
      intracellular stages, the wall-forming bodies of macrogametes and the outer
      oocyst walls all shared these epitopes. The antigens that bear these epitopes
      were characterized using the whole oocyst and sporozoite stages as sources of
      antigenic material. Complex labelling patterns were observed on Western blots.
      However, all the mAbs used in this study recognized an antigen of more than 500
      kDa. The glycoproteinic nature of this antigen was demonstrated by its
      sensitivity to pronase and periodate treatments. The expression of this high
      molecular weight immunoreactive antigen in the intracellular stages of C parvum
      was not investigated and remains to be found.

PMID- 7522084
TI  - Antimalarials for Africa.

PMID- 7522085
TI  - Technical improvements in the staging of cancer: the role of imaging and contrast
      agents.
AB  - Despite advances in cancer diagnosis, there has been little impact upon outcome.
      This may be a consequence of the exceptional heterogeneity in cancers, especially
      their cell types, perfusion, oxygenation, and metabolic circumstances. Better
      therapeutic plans could require better characterization of individual tumors in
      individual patients. For some tumors, tissue characterization by sophisticated
      histologic analysis of biopsy samples may improve staging. However, noninvasive
      staging is more acceptable to patients and may be more comfortably repeated in
      the course of monitoring therapeutic regimens. Several imaging applications may
      serve these goals. First, new contrast agents may allow accurate cancer detection
      in regional lymph nodes. High resolution CT with perfluorocarbon lymphography is
      in the clinical trial stage. This could presage minimally invasive ablation of
      cancer in lymph nodes, as well. Second, new agents will better define local and
      metastatic cancers, also impacting standard and minimally invasive treatments.
      Finally, imaging methods may be able to measure perfusion and metabolism in small
      volumes in vivo, as well as estimate important local pharmacokinetics of
      therapeutics.

PMID- 7522082
TI  - Differential expression of transforming growth factor-beta 1 and beta 3 as well
      as c-fos mRNA in normal human prostate, benign prostatic hyperplasia and
      prostatic cancer.
AB  - The discrepancy between the incidence of latent prostate cancer and that of
      clinically overt carcinoma suggests that there can be different courses in the
      biological progression of prostate cancer. As this cancer is detected
      increasingly at an infraclinical stage, markers are needed to indicate which
      lesions will progress and lead to the patient's death. To investigate the
      possibility that specific growth factors and/or proto-oncogenes are expressed
      differentially, we measured mRNA levels of transforming growth factors beta 1
      (TGF-beta 1), TGF-beta 2 and TGF-beta 3 and of the c-fos and c-jun oncogenes by
      Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and
      prostate cancer. Our data demonstrate that expression of TGF-beta 1 increased,
      whereas that of TGF-beta 3 fell to an almost undetectable level in carcinoma.
      Expression of c-fos followed the TGF-beta 1 pattern, whereas no difference could
      be seen in c-jun expression in cancer as compared with BPH and normal prostate.
      The differential expression of TGF-beta 1, TGF-beta 3 and c-fos could possibly be
      used to improve the characterisation of prostate cancer. Long-term follow-up of
      patients may indicate whether mRNA levels of these growth factors and oncogenes
      correlate clinically and whether they can be used as markers for progression in
      human prostate cancer.

PMID- 7522087
TI  - Financial implications of excimer laser phototherapeutic keratectomy.

PMID- 7522086
TI  - [The inhibition of Mycoplasma pneumoniae adhesion in a fetuin test system by
      synthetic analogs and polymeric forms of neuraminic acid].
AB  - Eight glycosides and structural analogues of neuraminic acid as well as eight
      polymeric forms of N-acetyl neuraminic acid have been studied for their
      inhibitory effect on adhesion of Mycoplasma pneumoniae. Maximum inhibiting effect
      among low-molecular compounds was manifested by 2-->3 sialyllactose which, being
      used in concentrations 5.0 and 10.0 micrograms/ml, inhibited adhesion of
      mycoplasmas by 76 and 87%, respectively. These indices for other derivatives in
      the above mentioned concentrations were as follows (%): 2-->6 sialyllactose, 31
      and 74%; alpha-Me-glycoside NeuAc, 75 and 85%; alpha-Bn-glycoside-N
      trifluoruracetyl NeuAc, 30 and 63%; alpha-Bn-glycoside NeuAc, 32 and 59%; alpha
      Bn-glycoside-4-epi-NeuAc, 20 and 27%; beta-Bn-glycoside NeuAc, 2-4%; beta-me
      glycoside NeuAc, 4-5%. The maximum inhibiting effect (50% inhibition at
      concentration 2.5 mumol) among polymeric forms was exerted by the conjugate alpha
      benzeneglycoside with polyacrylic acid containing 12 mol% of NeuAc. Conjugates
      with 8, 16 and 20 mol% of NeuAc possessed a bit less activity. The 50%
      concentration for them was 5.3, 3.1 and 8.3 mumol, respectively. Polymeric forms
      on the basis of polyacrylamide proved less active.

PMID- 7522088
TI  - Effect of nitrogen flow on recovery of vision after excimer laser photorefractive
      keratectomy without nitrogen flow.
AB  - BACKGROUND: Excimer laser (VISX) photorefractive keratectomy was performed using
      nitrogen flowing through the ocular fixation ring. It was felt that eliminating
      nitrogen flow may provide faster early visual rehabilitation. METHODS: Two groups
      of 50 consecutive eyes underwent photorefractive keratectomy with (N2 flow) and
      without (no N2 flow) nitrogen flow, and were evaluated at 1 month
      postoperatively. RESULTS: There were more under- or overcorrections exceeding
      1.00 diopter (D) in the N2 flow than in the no N2 flow groups. Eighteen eyes in
      the N2 flow and 11 in no N2 flow groups saw 20/50 or less, without correction.
      Fourteen eyes in the N2 flow and nine eyes in the no N2 flow groups lost two or
      more lines of best spectacle-corrected visual acuity. Four eyes in the N2 flow
      and none in the no N2 flow groups increased more than 1.00 D of astigmatism.
      CONCLUSION: The elimination of nitrogen flow in photorefractive keratectomy
      performed with the VISX laser appears to improve visual results in the early
      postoperative period.

PMID- 7522089
TI  - Induction of astigmatism by straight transverse corneal incisions, 45 degrees
      long, at different clear zones in human cadaver eyes.
AB  - BACKGROUND: Two of the major factors affecting the amount of astigmatism
      correction are the length of the transverse incision and its distance from the
      center of the cornea. Many nomograms used in clinical practice have been created
      by varying the length or clear zone diameter of the incisions. A simplification
      of this situation has been suggested by Thornton, who has theorized that straight
      transverse incisions, subtending 45 degrees of arc, have equal astigmatic
      corrective effect at different clear zones. Our study tested Thornton's theory in
      human donor eyes. METHODS: Ten eyes were tested at four clear zones: 5.0, 6.0,
      7.0, and 8.0 mm. Paired straight transverse incisions, subtending an arc of 45
      degrees (2.1 to 3.3 mm long), were centered on the 90-degree meridian.
      Preoperative keratometric readings at the 180- and 90-degree meridians were
      compared to the postoperative readings; the difference was the total astigmatism
      induced. We also calculated the coupling ratio. RESULTS: Student's t-tests
      comparing clear zones 6.0 and 7.0 mm revealed a statistical difference (p =
      .0085) in total astigmatic induction, greater for the 6.0-millimeter zone. The
      coupling ratio decreased as the clear zone diameter increased, presumably as a
      result of diminished flattening effect along the incised meridian. One-way
      analysis of variance indicated that the groups were different (p = .0001), and
      that the theory noted above was incorrect. CONCLUSIONS: The effect of transverse
      incisions subtending the same angular length, drops off dramatically with clear
      zones larger than 6.0 mm, contrary to the theory of Thornton. This effect may be
      due to reduction in coupling as the clear zone diameter increases, suggesting
      that the greatest efficacy is achieved for transverse incisions placed between
      5.0- and 6.0-millimeter zones.

PMID- 7522091
TI  - Refractive stability after cataract extraction using a 6.5-millimeter scleral
      pocket incision with horizontal or radial sutures.
AB  - BACKGROUND: Radial suturing of 6.5-millimeter scleral tunnel incisions following
      cataract surgery can create significant with-the-rule astigmatism in the
      immediate postoperative period. Because of the significant visual distortion and
      slow visual recovery seen with radial suturing, this study was undertaken to
      compare two other suturing techniques which induce lesser amounts of with-the
      rule astigmatism in the immediate postoperative period. METHODS: The refractive
      behavior of eyes closed with loose radial sutures and with horizontal sutures was
      compared to the behavior of eyes closed with the more traditional "tight" radial
      sutures following phacoemulsification surgery. RESULTS: Eyes sutured with loosely
      tied radial sutures demonstrated minimal with-the-rule cylinder immediately
      following surgery (1.25 D) and showed a more rapid stabilization of astigmatism
      than did the eyes tied with tight radial sutures, 2 months versus up to 6 months.
      However, the eyes tied with horizontal sutures, which showed no induced with-the
      rule astigmatism at the time of surgery, showed even more rapid stabilization
      between 5 days and 1 month from the time of surgery. CONCLUSION: To get the most
      rapid visual rehabilitation following cataract surgery, a wound closure which
      generates no induced with-the-rule cylinder such as horizontal sutures would be
      required.

PMID- 7522090
TI  - Evaluation of night vision disturbances.
AB  - BACKGROUND: Evaluation of night vision disturbances has relied on subjective
      responses. We designed a test to more objectively measure night vision
      disturbances. METHODS: The test consisted of projecting a small circle onto a
      visual acuity screen. The patient is asked to draw exactly what he sees on an
      Amsler grid. We evaluated 118 eyes in photopic and scotopic conditions and under
      different conditions of refractive correction. RESULTS: Image degradation
      increased in scotopic conditions for myopes (p = .0001), hyperopes (p = .005),
      and emmetropes (p = .01). Myopic refractive error correlated with size of glare
      response (p = .001). Astigmatism correlated with decentration of glare response
      (p = .0001). Decentration increased in scotopic compared to photopic conditions
      (p = .002). CONCLUSION: Our test offers a simple, convenient way to evaluate
      night vision disturbances and may offer a means of assessing night vision
      disturbances in patients considering refractive surgery.

PMID- 7522092
TI  - Biomechanical behavior of the cornea and its response to radial keratotomy.
AB  - BACKGROUND: Radial keratotomy reduces myopia by flattening the central cornea,
      but the mechanism remains a matter of controversy. In this article, we studied
      the biomechanical behavior of the cornea and its response to radial keratotomy.
      METHODS: A human cadaver eye model without corneal epithelium was used in this
      study. We studied the effects which varying intraocular pressure (IOP) and
      corneal hydration would have on the keratometric power of unoperated eyes and
      eyes following radial keratotomy. For nonoperated eyes, first, normal corneal
      hydration was maintained while the IOP was varied. Second, the IOP was maintained
      at a constant level of 20 mm Hg while the corneal hydration was changed. The
      effects of separately varying the IOP and corneal hydration of postoperative eyes
      following an eight-incision radial keratotomy were studied in a similar fashion.
      RESULTS: In the nonoperated eye, a very high IOP was associated with a general
      reduction of corneal astigmatism without significantly affecting the overall
      keratometric spherical equivalent refraction. A steepening change of less than
      0.50 diopters (D) was obtained in all eyes when dehydrating the cornea from 700
      +/- 50 microns (centrally) and 830 +/- 70 microns (peripherally), to 495 +/- 25
      microns (centrally) and 655 +/- 45 microns (peripherally). Following radial
      keratotomy, changes in IOP within the physiological range were found to have
      minimal influence (< 0.50 D) on the radial keratotomy keratometric power.
      However, after hydrating the cornea with balanced salt solution for 30 minutes,
      we obtained a mean flattening of 10.00 D. When dehydrating these corneas with
      topical hyperosmotic solution over a period of 3.5 hours, the flattening reversed
      to near preoperative values. The change in keratometric power resulting from
      radial keratotomy was significantly modulated by varying the hydration state of
      the deepithelialized cornea: the greater the hydration, the flatter the central
      cornea; therefore, the unpredictable surgical outcomes and diurnal fluctuations
      observed after radial keratotomy may be affected by applying topical hyperosmotic
      agents. CONCLUSIONS: We hypothesize that the corneal stroma is an inelastic,
      anisotropic, layered collagen structure that distributes tensile stress unequally
      throughout its thickness as a function of the amount of hydration. IOP, within
      physiological levels, did not have a significant effect on corneal flattening.

PMID- 7522094
TI  - Corneal ectasia as a complication of repeated keratotomy surgery.
AB  - BACKGROUND: Staged keratotomy surgery, or "enhancement surgery," may allow a more
      predictable outcome, but also subjects the patient to additional surgical risks.
      METHODS: A 39-year-old man underwent astigmatic keratotomy for myopic
      astigmatism, followed by 12 enhancement procedures for residual astigmatism.
      RESULTS: These procedures effectively resulted in a double hexagonal keratotomy.
      The patient's best spectacle-corrected acuity deteriorated to counting fingers.
      Clinically, a conically-shaped protrusion of the central cornea, Munson's sign,
      diffuse subepithelial scarring, and central corneal thinning were noted.
      Penetrating keratoplasty was performed. Histopathologic examination showed
      central thinning, epithelial edema, disruption of Bowman's layer, marked stromal
      scarring, and focal areas of endothelial attenuation--findings consistent with
      keratoconus. CONCLUSION: This case illustrates that multiple keratotomy
      procedures may result in corneal ectasia in apparently normal eyes and suggests
      that hexagonal keratotomy may be more likely to cause iatrogenic keratoconus.

PMID- 7522095
TI  - A surgical technique for the treatment of central corneal perforations.
AB  - BACKGROUND: Generally, corneal perforations of 2 mm in diameter or greater are
      treated using graft material for tectonic support. A surgical technique for the
      primary repair of such perforations without the use of any additional tissue is
      presented. METHODS: This procedure is demonstrated by a case report. The
      technique involves creation of an elliptical defect out of a circular one, thus
      allowing for primary closure, with the addition of glue. A definitive penetrating
      keratoplasty was subsequently performed with several important modifications
      described herein. RESULTS: A water-tight closure was obtained with this technique
      for 1 month while the inflammation subsided. Preoperative visual acuity was light
      perception. One year postoperatively, it was count fingers at 8 feet with mild
      irregular astigmatism. CONCLUSION: This technique is useful for perforations
      which are central, larger than 2 mm in diameter, and when corneal or scleral
      material is not readily available for patch grafting.

PMID- 7522093
TI  - Corneal epithelial dots following excimer laser photorefractive keratectomy.
AB  - BACKGROUND: Map-dot-fingerprint epithelial changes of the cornea have been
      reported to occur as a consequence of trauma or surgical procedures, such as
      radial keratotomy. METHODS: We describe a case of dot-like changes in the corneal
      epithelium following excimer laser photorefractive keratectomy for the correction
      of myopia. Because the lesions were located centrally, possibly reducing visual
      acuity, the epithelium was removed mechanically. RESULTS: Dot-like changes
      recurred in the same areas 4 weeks after epithelial debridement. Best spectacle
      corrected visual acuity improved from 20/200 to 20/100 and remained stable
      thereafter. CONCLUSIONS: Photorefractive keratectomy can lead to abnormal
      regeneration of epithelium basement membrane, possibly resulting in dot-like
      changes of corneal epithelium.

PMID- 7522096
TI  - Excimer laser photorefractive keratectomy for treatment of keratoconus.
AB  - BACKGROUND: Five eyes with keratoconus that were scheduled for penetrating
      keratoplasty were treated instead with excimer laser photorefractive keratectomy
      to reduce the steepness of the cone. The follow up after 6 to 12 months is
      reported here. METHODS: A 193-nanometer excimer laser system VISX 20/20 was used
      for correction of myopia or astigmatism. The patients had a complete
      ophthalmological examination including slit-lamp microscopy and
      videokeratography. The patients were followed with six examinations during a
      period of at least 6 months. RESULTS: In four eyes, a reduction of the
      astigmatism was achieved with an increase of visual acuity. There were no
      problems with wound healing or any signs that the excimer adversely affected the
      cornea or activated the keratoconus disease process. CONCLUSION: The treatment of
      keratoconus with excimer laser has been regarded as seriously contraindicated on
      a speculative basis. This risk seems to be exaggerated.

PMID- 7522097
TI  - Refractive surgery goes mainstream: establishing radial keratotomy services at a
      suburban community hospital.

PMID- 7522100
TI  - Expression of differentiation markers in human adult keratinocytes cultured in
      submerged conditions.
AB  - A number of studies have shown that human keratinocytes cultured in submerged
      conditions with non-delipidized serum do not express the major differentiation
      markers, i.e. 67 kDa keratin, ceramides, and lanosterol. However, they were
      mostly performed with neonatal or juvenile keratinocytes after a few passages,
      and not all the markers were analyzed in parallel. In this study, we compared the
      expression of several differentiation markers in preconfluent and postconfluent
      adult breast keratinocytes in primary and secondary cultures before and after
      cryopreservation. When primary cultures reached confluence, the 67 kDa keratin
      was synthesized, transglutaminase activity was increased, and, although overall
      lipid synthesis dropped, both lanosterol and free fatty acids contents were
      augmented. The same pattern was observed in postconfluent subcultures at Passage
      2; however decreased overall lipid synthesis was more pronounced.
      Cryopreservation of keratinocytes just after isolation or after a few days in
      culture did not result in the loss of expression of these specific epidermic
      markers. Thus, adult breast keratinocytes in postconfluent submerged cultures
      represent an in vitro model that possesses various features of the normal
      epidermis, even after cryopreservation.

PMID- 7522099
TI  - Expression of some hepatocyte-like functional properties of WRL-68 cells in
      culture.
AB  - Some morphologic and functional characteristics of an hepatic fetal human
      epithelial cell line (WRL-68 cells) were determined to validate the use of these
      cells as an in vitro hepatic model. WRL-68 cells have a morphologic structure
      similar to hepatocytes and hepatic primary cultures. They secrete alpha-feto
      protein and albumin and exhibit a cytokeratin pattern similar to other hepatic
      cultures. WRL-68 cells preserve the activity of some characteristic or specific
      liver enzymes or both used in clinical chemistry for the diagnosis of hepatic
      disorders, i.e. alanine amino transferase, aspartate amino transferase, gamma
      glutamyl transpeptidase, and alkaline phosphatase.

PMID- 7522101
TI  - Isolation and characterization of vasoformative endothelial cells from the rat
      aorta.
AB  - We describe here a modified nonenzymatic method for the isolation of rat aortic
      endothelial cells with vasoformative properties. Aortic rings placed on plastic
      or gelatin-coated surfaces generated outgrowths primarily composed of endothelial
      cells. Prompt removal of aortic explants after endothelial migration minimized
      fibroblast contamination. However, fibroblasts, because of their high
      proliferative rate tended to overgrow the endothelial cells even when present in
      small numbers. This potential pitfall was avoided by weeding out fibroblasts with
      the rounded tip of a bent glass pipette. Primary endothelial colonies free of
      fibroblasts were segregated in cloning rings, trypsin-treated, and transferred to
      gelatin-coated dishes. Endothelial cells were cultured in MCDB 131 growth medium
      containing 10% fetal bovine serum, endothelial cell growth supplement, and
      heparin. Using this technique, pure endothelial cell strains were obtained from
      single aortic rings. Confluent endothelial cells formed a contact-inhibited
      monolayer with typical cobblestone pattern. The endothelial cells were positive
      for Factor VIII-related antigen, took up DiI-Ac-LDL, and bound the Griffonia
      Simplicifolia-isolectin-B4. Endothelial cells cultured on collagen gel formed a
      polarized monolayer, produced basement membrane, displayed Weibel-Palade bodies
      and caveolae, and were connected by tight junctions. In addition, they
      reorganized into a network of microvascular cords and tubes when overlaid with a
      second layer of collagen and formed microvascular sprouts in response to
      fibroblast-conditioned medium. This isolation procedure yields stable strains of
      vasoformative endothelial cells, which can be used to study aortic endothelium
      related angiogenesis and its mechanisms.

PMID- 7522102
TI  - Expression of endothelial cell adhesion molecules in human bronchial xenografts.
AB  - The role of endothelial cell adhesion molecules (CAMs) in the selective
      recruitment of leukocyte subsets to the airway remains unclear. The goal of the
      present study was to examine the expression of human endothelial CAM in a
      cytokine-induced airway inflammatory response. To accomplish this, an in vivo
      model of human bronchus was developed by heterotopically transplanting intact
      sections of human airway into severe combined immunodeficient (SCID) mice. Three
      weeks after transplantation, the xenografts closely resembled normal bronchus
      with little evidence of rejection. Less than 15% of the submucosal vessels
      expressed E-selectin and vascular cell adhesion molecule-1 (VCAM-1), whereas
      intercellular adhesion molecule-1 (ICAM-1) was present constitutively on
      approximately 35% of bronchial microvessels. Intrabronchial instillation of tumor
      necrosis factor-alpha (TNF-alpha) significantly increased expression of
      microvascular E-selectin to 40%, ICAM-1 to 65%, and VCAM-1 to 41%, and was
      accompanied by an influx of murine leukocytes into the bronchial submucosa. These
      results demonstrate that the human bronchial microvasculature expresses cytokine
      inducible adhesion molecules. Mast cells and other resident or migratory cells
      that secrete TNF-alpha may thus activate the bronchial microvasculature and
      thereby recruit leukocytes to the airway.

PMID- 7522098
TI  - Endothelial change after excimer laser photorefractive keratectomy.

PMID- 7522103
TI  - A freeze-injured skin graft model for the quantitative study of basic fibroblast
      growth factor and other promoters of angiogenesis in wound healing.
AB  - A new in vivo model has been developed for the quantitative study of promoters
      and potential promoters of angiogenesis. Full thickness rat skin autografts
      received a reproducible and uniform freeze injury, before being applied to full
      thickness wounds, in order to delay revascularisation. Blood flow in the grafts
      was measured during the healing period using noninvasive (laser Doppler
      flowmetry) and invasive (133Xe clearance) techniques. The increase in blood flow
      over a period of 10-14 days was taken as an index of angiogenesis. These
      measurements were corroborated by histological assessment of the graft
      vasculature, using a laminin stain to highlight vascular basement membrane.
      Freeze injury delayed but did not ultimately prevent full graft revascularisation
      (p < 0.01 for laser Doppler flowmetry and 133Xe clearance). Application of the
      angiogenic agent basic fibroblast growth factor (bFGF), in slow release pellet
      form, stimulated angiogenesis in cryoinjured grafts in a dose-related fashion.
      Doses of 500 and 5000 ng bFGF produced significant stimulation (500 ng bFGF, p <
      0.001, and 5000 ng bFGF, p < 0.01, for both laser Doppler flowmetry and 133Xe
      clearance; increased vessel profile counts, p < 0.05, at each time point tested
      for both doses) while 50 ng bFGF had no significant effect. By contrast, 500 ng
      bFGF had no measurable effect on uninjured grafts. In addition, bFGF-stimulated
      angiogenesis in cryoinjured grafts was antagonised by a neutralising antibody to
      bFGF, demonstrating the specificity of action of bFGF in this model.

PMID- 7522105
TI  - News from "the real world": cost-effectiveness in palliative care.

PMID- 7522104
TI  - Competitive antagonism by phenylglycine derivatives at type I metabotropic
      glutamate receptors.
AB  - The metabotropic glutamate receptors (mGluRs) form a family of G-protein-coupled
      receptors which consists of at least seven members termed mGluR1-mGluR7. These
      members are classified into subfamilies according to their sequence similarities,
      signal transduction mechanisms and agonist selectivities. mGluR1 and mGluR5 are
      coupled to the phosphoinositide hydrolysis/Ca2+ signal transduction and
      efficiently respond to quisqualate. In this study, we have stably expressed
      mGluR1 in Chinese hamster ovary cells on which the activation of the
      phosphoinositide signal transduction pathway was evaluated by means of two
      methods and their degree of correspondence was analyzed. These two methods
      involve the Li(+)-dependent accumulation of [3H]inositol-labeled inositol
      phosphates or the [3H]cytidine-labeled phospholiponucleotide cytidine diphospho
      (CDP)- diacylglycerol (DAG). The correlation between the two measures was found
      to be generally uniform for the different agonists evaluated. However, the levels
      of CDP-DAG were found to be consistently higher. Furthermore, quisqualate showed
      a differential activity on the two methods behaving as a partial agonist and as a
      full agonist on the inositol phosphate and the CDP-DAG responses, respectively.
      On the same cells the activity of a series of carboxyphenylglycines recently
      described as possible new tools for investigating the role of mGluRs has been
      evaluated. Three phenylglycine derivatives were tested and found to be
      competitive antagonists at this mGluR subtype. They inhibited both the
      phosphoinositide signal transduction pathway and the release of intracellular
      Ca2+ induced by quisqualate the most potent agonist at mGluR1. The
      pharmacological nature of these compounds and their relative potencies in
      antagonizing mGluR1 activation are described.

PMID- 7522107
TI  - Positive selection of CD34+ cells: a short review of the immunoadsorption methods
      currently available for experimental and clinical use. Report on the "2nd
      European Workshop on stem Cell Methodology," Mulhouse, France, May 3-7, 1993.
AB  - At the "2nd European Workshop on Stem Cell Methodology," held in Mulhouse,
      France, on May 3-7, 1993, part of the meeting was dedicated to the positive
      selection of CD34+ cells. All devices that are currently in use, or will be
      available in the near future, were explained and practically demonstrated using
      human cell populations by scientists involved in their development. In this
      paper, a review of these methods is given in the form of a short description,
      together with the data presented in Mulhouse and available from the literature.

PMID- 7522111
TI  - A strategy for processing of peripheral blood stem cells utilizing the small
      volume collection chamber and cryopreservation without a rate controller using
      pentastarch.
AB  - Standardization of protocols for processing peripheral blood stem cells (PBSC)
      will be important for multiinstitutional studies. For this reason, a strategy was
      developed utilizing the small volume collection chamber (SVCC) in the Fenwal CS
      3000 PLUS Blood Cell Separator and cryopreservation without a rate controller in
      medium containing pentastarch. Use of the SVCC allows for a small extracorporeal
      volume, extraction of a minimal number of platelets, and a high efficiency of
      mononuclear cell (MNC) removal. Advantages of the pentastarch cryopreservation
      technique include reduction in technician time compared to controlled rate
      cryopreservation and use of lower concentrations in DMSO. Clinical studies using
      the SVCC and pentastarch technique demonstrate that these goals have been
      accomplished. Furthermore, patients transplanted with cells that were processed
      by this technique engrafted faster and were discharged sooner than patients
      receiving autologous bone marrow transplants.

PMID- 7522109
TI  - Peripheral blood stem cell autografts for the treatment of childhood cancer: a
      review of the Japanese experience. Japanese Cooperative Study Group of PBSCT
      (JCSG/PBSCT).
AB  - Harvesting peripheral blood stem cells (PBSC) for autografts (PBSCT) in children
      with active cancers is a safe and reliable procedure with a low incidence of
      serious morbidity. A significant correlation between the number of infused CFU-GM
      and the time to both granulocyte and platelet engraftment was found. Cells
      induced by G-CSF could speed the recovery of granulocyte or platelet counts after
      PBSCT. In terms of preserving engraftment potential, cryopreservation of PBSC by
      a simplified uncontrolled-rate method is at least as effective as the traditional
      controlled-rate freezing procedure with a programmed freezer. As the serum G-CSF
      level increases immediately following infusion of PBSC graft, therapy with G-CSF
      may have only a limited ability to further enhance hematopoietic recovery after
      PBSCT. Preliminary results of high-dose chemotherapy without TBI and PBSCT for
      the treatment of children with relapsed ALL are encouraging.

PMID- 7522108
TI  - Expression of adhesion molecules and c-kit on CD34+ hematopoietic progenitor
      cells: comparison of cytokine-mobilized blood stem cells with normal bone marrow
      and peripheral blood.
AB  - We assessed the expression of the adhesion molecules leukocyte function antigen-1
      (LFA-1, CD11a), intercellular adhesion molecule-1 (ICAM-1, CD54), homing
      associated cell adhesion molecule (H-CAM, CD44), and c-kit (stem cell factor
      receptor) on the CD34+ progenitor population from the leukapheresis products of
      23 patients (LP CD34+). For blood stem cell collection granulocyte colony
      stimulating factor (G-CSF) or interleukin-3/granulocyte-macrophage colony
      stimulating factor (IL-3/GM-CSF) was administered after cytotoxic chemotherapy.
      Furthermore, bone marrow- and blood-derived CD34+ progenitor cells from 6 normal
      volunteers (BM and PB CD34+) were analyzed. LFA-1 expression was higher on PB
      CD34+ (88.2 +/- 2.5%, mean +/- SEM) than on BM CD34+ (75.3 +/- 4.3%). Following
      cytokine administration, LFA-1 was expressed on only 59.7 +/- 3.7% of LP CD34+ at
      a low fluorescence intensity, suggesting that down-regulation of LFA-1 may
      facilitate the egress of cells from the bone marrow and prolong their
      circulation. In contrast, ICAM-1 was weakly positive on CD34+ cells from all
      sources. CD44 was expressed on the vast majority of CD34+ cells (> 95%) in all
      samples studied. The highest proportion of CD34+ cells costaining for c-kit was
      found in normal bone marrow (32.2 +/- 3.3%). In normal peripheral blood and after
      cytokine mobilization, fewer of the CD34+ cells weakly expressed c-kit (< 15%).
      The low percentage and level of c-kit expression may indicate that the majority
      of cytokine-mobilized CD34+ cells are lineage-committed progenitor cells, as
      reflected by the coexpression pattern for CD38, HLA-DR, and CD33.

PMID- 7522106
TI  - What do advanced cancer patients know of their disease? A report from Italy.
AB  - The aim of this work was to investigate the awareness of diagnosis, prognosis and
      meaning of palliative treatment in Italian patients with advanced, incurable
      cancers. A group of 100 patients, referred to a Medical Oncology facility, were
      interviewed. Only 38 patients were aware of the malignant neoplastic nature of
      their disease. The remaining patients believed they had a benign neoplasia, non
      neoplastic disease, or were unable to define their illness. No patient had a
      correct idea of the poor prognosis of the disease. Only 11.5% of 87 patients
      receiving chemotherapy had a correct perception of the palliative intent of the
      treatment, while most believed that the chemotherapy was "preventive".
      Dissatisfaction with the information received was expressed by a minority of
      patients. The awareness of diagnosis was better among women and patients with a
      higher educational background. Withholding the truth from cancer patients still
      seems very common in Italy.

PMID- 7522113
TI  - Combined modality treatment for locally advanced non-small cell lung cancer-
      which control arm?
AB  - Up to one-third of newly diagnosed patients with non-small cell lung cancer
      (NSCLC) present with locally advanced, unresectable disease. Traditionally, these
      patients have been treated with thoracic radiotherapy alone. Unfortunately, the
      vast majority eventually die as a result of the development of distant,
      extrathoracic metastases. While chemotherapy is not particularly effective
      against clinically obvious metastatic disease, there are good theoretical reasons
      why the use of this modality in earlier stage disease may be beneficial. Several
      recently completed pilot studies of combined modality therapy have yielded
      promising results suggesting improved survival. Indeed, the combination of
      chemotherapy and thoracic radiotherapy has been shown to be marginally superior
      to radiotherapy alone in a few recently completed randomized trials. However,
      this has not been a uniform observation. Thus, further study is needed to firmly
      establish the role of combined modality treatment in Stage III, unresectable non
      small cell lung cancer. In these future trials, the best control arm is a matter
      of some controversy.

PMID- 7522110
TI  - Source of stem cell rescue: bone marrow versus peripheral blood progenitors.
AB  - Sustained hematopoiesis can be restored after dose-intensive chemotherapy
      utilizing stem cells from either bone marrow and/or peripheral blood. Numerous
      reports have demonstrated the effectiveness of peripheral blood progenitors
      (PBPC) in restoring hematopoiesis. Here, we review data comparing the recovery
      among patients rescued with various stem cell sources after dose-intensive
      therapy. PBPC used alone or to augment autologous bone marrow to achieve timely
      hematopoietic recovery after dose-intensive therapy can result in shortened
      hospital stays, decreased transfusion requirements, and antibiotic usage. This
      will lead to increased application of dose-intensive therapy either singly or in
      multiple courses to treat various malignancies.

PMID- 7522114
TI  - New perspectives in combined radiotherapy and chemotherapy treatment.
AB  - Strategies for developing combined modality treatment for lung cancer have, until
      now, depended largely on empirical approaches whereby drugs with some activity
      against advanced disease have been combined with radiation. Survival gains have
      been modest. The present article emphasizes the need for new approaches that are
      based on mechanisms of interaction or cooperation between radiation and drugs,
      such that there is a selective increase in killing of tumour cells. Potential
      interactions include the use of radiation and drugs to eliminate cell populations
      which are shown in predictive assays to have differing mechanisms of resistance
      to the two modalities, selective inhibition of repopulation of tumour cells
      during radiotherapy by using drugs or biological agents, and selective killing of
      cells in hypoxic or acidic regions of tumours. The feasibility and potential of
      such approaches should be evaluated initially in small single-arm studies where
      outcome in individual patients is related to biological studies of mechanism.
      Such treatment may need to be individualized (e.g. depending on markers of drug
      resistance or growth factor receptors). Ultimately, the value of such treatments
      will need to be evaluated (whether individualized or generic) against standard
      treatment in large randomized trials. Guidelines for the conduct of such trials
      are indicated with emphasis on quality of life, assessment of costs and benefits,
      and involvement of patients in clinical decision making.

PMID- 7522116
TI  - Somatostatin specifically binds p86 subunit of the autoantigen Ku.
AB  - The heterodimer Ku, first described as a nuclear autoantigen, is a regulatory
      factor of DNA replication and transcription. We have expressed the p86 subunit of
      Ku in Escherichia coli as a fusion protein with glutathione-S-transferase, using
      the vector pGEX-2T. After splitting up by thrombin, p86 was isolated by Sephacryl
      S200 gel filtration. The recombinant protein was found to have the same
      electrophoretic migration and to react with the same monoclonal antibody as the
      somatostatin-binding protein we recently isolated from the human gastric tumor
      cell HGT1 [7]. Furthermore, using the analog [125I]Tyr-11 somatostatin-14 as a
      tracer, we found that, like the HGT1 cell-purified protein, recombinant p86
      specifically bound somatostatin with high affinity (KD = 2.3 +/- 0.3 nM) and
      large capacity (10,300 +/- 1,700 pmol/mg protein). These findings suggest that
      p86 subunit of Ku stands for the protein we previously isolated from the HGT1
      cell. It could represent a new somatostatin receptor subtype perhaps involved in
      the antimitogenic effect of this peptide.

PMID- 7522112
TI  - Large volume leukapheresis to maximize peripheral blood stem cell collection.
AB  - Large volume leukapheresis, defined as the processing of greater than three
      volumes of blood at one sitting, can be safely and easily performed using a
      variety of cell separators in a range of patients. This paper describes the
      history, technique, outcome, complications, and proposed uses for this procedure.

PMID- 7522115
TI  - Tenascin glycoproteins in neural pattern formation: facets of a complex picture.
AB  - It is generally accepted that neuron-glia interactions play an important role in
      the regulation of neural development. For example, astrocytes are thought to
      guide migrating neuronal precursors and advancing growth cones to their
      destination. In addition, astrocytes have recently been ascribed a function in
      the segregation of forming neuronal assemblies and fiber tracts and are believed
      to hinder regeneration of lesioned adult central nervous system (CNS) structures.
      Therefore molecules that might specifically mediate neuron-glia interactions in
      the CNS attract considerable interest. The growing family of tenascin
      glycoproteins may play a key role in this context. Tenascin glycoproteins are
      transiently expressed by astrocytes in the nervous system and affect neuronal
      morphogenesis and behavior in definable ways. The present review discusses
      functional properties and examines seemingly contradictory effects of these
      extracellular matrix constituents.

PMID- 7522117
TI  - [Mechanism of proliferation of cells transformed by the Moloney mouse sarcoma
      virus after stable reversion to a non-malignant state].
AB  - Prolonged interferon (IFN) treatment can convert Moloney sarcoma-transformed
      mouse Balb C fibroblasts to a stable non-malignant status. The cells recover a
      number of differentiated features, which are maintained even when IFN is
      permanently omitted from the tissue culture medium. We show here that reversion
      could be at least in part attributed to constitutive IFN beta synthesized only in
      the reverted cells. The continued replication of these cells, although unable to
      induce tumours in athymic mice, could be the result of the maintained expression
      of an IFN antagonist termed sarcolectin (SCL), a balance being struck between the
      effects of v-mos oncogene, interferon beta and SCLs. In agreement with Lampl et
      al. [11], we suggest that normal cell growth is discontinuous, consisting of
      sudden bursts followed by prolonged arrests which could be necessary to promote
      differentiation during the ensuing interphase.

PMID- 7522118
TI  - Immunological identification of a 50 kDa Mr FK506-binding immunophilin as a
      component of the non-DNA binding, hsp90 and hsp70 containing, heterooligomeric
      form of the chick oviduct progesterone receptor.
AB  - p59/HBI, a Heat shock protein (hsp90)-Binding-Immunophilin of approximately 59
      kDa, was originally detected in the heterooligomeric, non-DNA binding form of
      numerous mammalian steroid hormone receptors. P59/HBI belongs to the FKBP family
      since it binds the immunosuppressants FK506 and Rapamycin. Using immobilized
      FK506, we purified [3H]Org 2058-progesterone receptor (PR)-hsp90-complexes from
      chick oviduct cytosol in a species migrating at 9S in density gradient. This led
      to suppose that a protein present in these complexes is a FK506 binding protein.
      Following incubation of this FK506-affinity purified 9S-PR with BF4, a specific
      anti-chick hsp90 monoclonal antibody, a shift of the [3H]Org 2058-PR complexes
      from 9S to 11S has been observed, indicating the presence of hsp90, hsp70 also is
      included in the 9S-PR complexes as demonstrated by Western blotting and density
      gradient experiments. Two lines of evidence support the notion that an
      immunophilin of 50 kDa also associates to heterooligomeric 9S-PR complexes.
      Firstly, a shift at 11S of the FK506 eluted 9S-PR occurs in sucrose gradient
      after incubation with 419, a new polyclonal antibody raised against a peptide
      corresponding to the Hinge I region [Callebaut I., Renoir J. M., Lebeau M. C.,
      Massol N., Burny A., Baulieu E. E., Mornon J. P. (1992) Proc. Natl. Acad. Sci.
      USA 89, 6270-6274] of the rabbit p59/HBI (amino acids Phe135 to Gly149).
      Secondly, in Western blotting experiments, both 419 and another anti-FKBP
      antibody, raised against purified Streptomyces Crysomallus FKBP12 [Pahl A. and
      Keller U. (1992) J. Bacteriol., 3, 325-333], allow detection of the same 50 kDa
      protein in the affinity purified PR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522119
TI  - [Inhibition of the anti-glucocorticosteroid effect of RU486 on the growth of
      mouse fibroblasts in culture by the immunosuppressor kf506]].
AB  - The growth of mouse L-929 fibroblasts in culture is inhibited by dexamethasone, a
      synthetic glucocorticosteroid, and this effect is itself suppressed by the
      antiglucocorticosteroid RU486 (mifepristone). Neither RU486 nor the
      immunosuppressant FK506 alone influence L-929 growth, and FK506 does not modify
      dexamethasone action. However, FK506 suppresses the antiglucocorticosteroid
      activity of RU486. The implication of the "anti-antagonist" activity of FK506 in
      its immunosuppressant properties has still to be explained. The role of the
      recently cloned, FK506-binding, p59 immunophilin, which binds to the heat shock
      protein hsp90 which itself interacts with the glucocorticosteroid receptor, is
      discussed.

PMID- 7522122
TI  - Prostate cancer screening. Appropriate choices? Investigators of the American
      Cancer Society National Prostate Cancer Detection Project.
AB  - Early detection of prostate cancer has produced distinct stage migration of
      prostate cancer to earlier, more curable disease through optimized combined use
      of digital rectal exam (DRE), transrectal ultrasound, and prostate specific
      antigen (PSA). Currently available and emerging data can be assessed according to
      the World Health Organization's established criteria. As a significant public
      health problem, prostate cancer meets almost all the criteria for screening.
      While concerns about incomplete natural history, progression rates, and the need
      for better prognostic factors are valid, important social and public health
      issues also need to be considered. If future expenditures for terminal cancer
      care are minimized via reductions in therapy choices or coverage, no economic
      benefit for prostate cancer screening should exist. Narrow-focused attempts at
      cost reduction could inappropriately discourage high risk groups from
      participating in early detection programs, thereby eliminating the greatest
      potential benefit. Conversely, the greatest immediate cost-control issue for
      prostate cancer care in the United States could be the marked increased detection
      in men older than 75 years of age. Current cost savings are possible with
      improved public health education about the appropriateness of early detection in
      the oldest age groups or those with significant preexisting medical conditions.
      Prostate cancer control perhaps requires a tailored approach of screening in high
      risk groups and more appropriate "case finding" in the lower risk, general
      population. The initial combination of PSA and DRE can result in early detection,
      which is both ethical and economic, for individual patients consulting with
      informed physicians.

PMID- 7522120
TI  - Concomitant chemoradiotherapy for advanced epidermoid carcinoma of the uterine
      cervix: a preliminary report.
AB  - BACKGROUND: Because the prognosis of advanced carcinoma of the uterine cervix is
      poor, and has improved very little in the last 20 years, a prospective study was
      initiated to evaluate the feasibility, response and toxicities of concomitant
      chemoradiotherapy for such cervical cancer. METHODS: From May 1992 to December
      1992, 22 patients entered the study, 21 of them completed the entire treatment.
      Their ages ranged from 47 to 72 years, median 57. There were 16 FIGO stage IIIB,
      and 5 stage IIB. Radiotherapy was administered using 1.8 Gy/day, five days a
      week, to the whole pelvis (50.4 Gy/28 fractions) with or without parametrial
      boost according to the tumor response. Intracavitary brachytherapy 5 Gy x five to
      six times was given after one or two weeks of rest. Chemotherapy consisted of
      etoposide 100 mg/m2 day 1 + cisplatin 50 mg/m2 day 1 + bleomycin 25 mg/m2/day day
      2-3, repeated every two weeks during external irradiation. RESULTS: All 21
      eligible patients achieved complete response, sustaining during a median follow
      up time of 12 months. All the initially elevated tumor markers (SCC, CEA, CA-125)
      returned to normal range after treatment. The toxicity was well tolerated.
      CONCLUSIONS: Concomitant chemoradiotherapy for advanced cervical carcinoma is
      both feasible and effective, with acceptable toxicities. Long-term follow-up is
      mandatory, and a randomized trial to confirm the superiority of this protocol
      will be started soon.

PMID- 7522121
TI  - Undernutrition in children with a neurodevelopmental disability. Nutrition
      Committee, Canadian Paediatric Society.
AB  - OBJECTIVE: To offer guidelines for optimal nutritional care in children with a
      neurodevelopmental disability and an associated impairment in their ability to
      eat and drink. OPTIONS: Assessment of nutritional status by skinfold thickness
      measurement, high-energy nutrition supplementation given orally and feeding by
      nasogastric tubes, gastrostomy tubes or gastrojejunal tubes. OUTCOMES: Children
      receiving adequate nourishment are generally calmer and appear more normal than
      those who are undernourished. Patients with less severe disabilities have an
      increased functional status with improved nutrition. In patients with
      gastroesophageal reflux and aspiration of food, the use of gastrojejunal tubes
      prevents pneumonia and reduces the need for surgery to correct the reflux.
      Economic benefits of various options were not considered. EVIDENCE: Members of
      the Nutrition Committee of the Canadian Paediatric Society, most of whom are
      involved in caring for children with a neurodevelopmental disability, reviewed
      the literature. Members interpreted the literature and developed the guidelines
      on the basis of their experience and research activities. VALUES: Improved
      psychologic, nutritional and functional status were all given a high value.
      BENEFITS, HARMS AND COSTS: Supplemental tube feeding allows caregivers to devote
      less time to feeding and more time to stimulating and educating children with
      this type of disability. The need for surgery to correct reflux, along with the
      associated risks and costs, has been greatly reduced with the development of
      percutaneous placement of the gastrostomy and gastrojejunal tubes.
      RECOMMENDATIONS: It is unacceptable not to treat undernutrition associated with a
      neurodevelopmental disability. Management of nutrition in patients who require
      tube feeding is greatly simplified by the use of percutaneous enterostomy. Energy
      needs in children with this type of disability are lower than in other children,
      ranging from 2900 to 4600 kJ per day. Because they require less energy, such
      children should be given a formula designed for children less than 6 years of age
      that has a high ratio of nutrients to energy. Every effort should be made to
      improve the oral-motor skills of children with a mild disability. VALIDATION: The
      guidelines were reviewed and approved by the board of the Canadian Paediatric
      Society. There are no equivalent guidelines from the Committee on Nutrition of
      the American Academy of Pediatrics.

PMID- 7522123
TI  - Surgical treatment options for colorectal cancer.
AB  - The aging of our national population is recognized as a major achievement of
      modern society. The National Institutes of Health have recently redefined "old"
      as beginning at age 70. This segment of our population lead active and productive
      lives. An unfortunate association of aging is the development of neoplasia. The
      incidence of colorectal cancer continues to escalate, with 150,000 cases expected
      each year, representing 15% of all cancer, two thirds of which are found in
      patients older than age 65. Forty percent of these patients present with advanced
      disease. Little change in survival by stage has been noted in the last 30 years.
      Surgical resection offers the only opportunity for cure as well as affording
      significant palliation in patients with advanced disease. Although age alone does
      not increase operative risks, comorbidity and emergency surgery are confounding
      factors. Repeated studies have shown that acceptable mortality and morbidity may
      be achieved by surgical resection for cure and for palliation in the elderly,
      thus age alone should not be a limiting factor. Key elements in management are
      early detection with surgical intervention before stage advancement or before
      complications occur (i.e., obstruction, perforation). When possible, comorbid
      factors, such as nutritional deficits, cardiovascular decompensation, and
      pulmonary insufficiency should be corrected. The appropriate use of mechanical
      bowel preparation and perioperative antibiotics should be emphasized. Surgical
      management should encourage adequate resection for cure or palliation rather than
      bypass or diversion. Proximal shifts in colon cancer location and improved
      technology frequently make resection with anastomosis possible rather than end
      colostomy. Multidisciplinary approaches to rectal cancer offer significant
      opportunities for sphincter preservation. Local excision with or without
      radiation therapy offers an occasional opportunity for treatment of rectal cancer
      in highly selective cases, also with sphincter preservation.

PMID- 7522124
TI  - The role of radiation therapy in the treatment of colorectal cancer. Implications
      for the older patient.
AB  - Radiation therapy plays an important role in the treatment of patients with
      colorectal cancer. Randomized trials show that patients with rectal cancer have
      an 8% improved local control rate with postoperative radiation and an 11-13%
      improved local control rate with combined postoperative radiation and
      chemotherapy. Survival is also improved for these patients. Ongoing randomized
      trials may clarify the role of postoperative radiation therapy for patients with
      colon cancer. Although there is little specific information regarding the
      tolerance and response of the older patient to radiation therapy, there is no
      reason to believe that cancer in the older patient is more sensitive to ionizing
      radiation. Therefore, treatment decisions should be based on the available data.
      The older patient may be at an increased risk for radiation-related small bowel
      damage, and the clinician should pay particular attention to techniques to limit
      the amount of small bowel in the irradiated field.

PMID- 7522125
TI  - The structure of the O-specific polysaccharide from Thiobacillus ferrooxidans IFO
      14262.
AB  - Lipopolysaccharide (LPS) was isolated from Thiobacillus ferrooxidans IFO 14262 by
      the hot phenol-water extraction procedure. The O-specific polysaccharide,
      liberated from LPS by mild acetic acid hydrolysis, had a branched pentasaccharide
      repeating-unit composed of D-glucose, L-rhamnose, D-rhamnose, and 3-O-methyl-L
      rhamnose in approximate molar ratios of 2:1:1:1. On the basis of methylation
      analysis, 1H and 13C NMR spectroscopy, including 2D shift-correlated (COSY) and
      1D NOE spectroscopy, the structure for the repeating unit of the O-specific
      polysaccharide was established, and the assumed biological repeating unit
      indicated.

PMID- 7522126
TI  - Epitopes for human monoclonal antibodies and serotyping antisera against the O
      specific polysaccharide of Pseudomonas aeruginosa O11.
AB  - Epitopes for Pseudomonas aeruginosa O11-specific human monoclonal antibodies
      (mAbs) and O11 serotyping antisera have been characterized. These mAbs recognized
      the O-polysaccharide portion of the lipopolysaccharide. The structure of the O
      polysaccharide of O11 has been reported to be comprised of trisaccharide
      repeating-units as follows: -->3)-alpha-L-FucpNAc-(1-->1)-beta-D-FucpNAc-(1--> 2)
      beta-D-Glcp-(1-->. (FucpNAc, 2-acetamido-2,6-dideoxygalactopyranoside.) Data from
      inhibition studies of binding in enzyme-linked immunosorbent assays and cell
      agglutination assays, using monosaccharides and periodate-oxidized O
      polysaccharide showed that the glucose residue, especially the C-3-C-6 segment
      and the beta-anomeric configuration, in the polysaccharide is essential for the
      epitopes of all anti-O11 mAbs; however, the detailed epitope specificities were
      different from one another. Furthermore, epitopes for serotyping antisera of O11
      seemed to be similar to those for the human mAbs.

PMID- 7522127
TI  - Characterization of the stability of human and murine thymic B cell/thymocyte
      rosettes and investigation of unusual immunophenotypic findings.
AB  - In this study we have used immunohistochemistry to study the controversial
      expression of CD2 and cytokeratin by thymic B cells and also the expression of
      the adhesion molecules CD40 and CD80. The B cells were clearly CD2 and
      cytokeratin negative, however the majority expressed CD40 and some coexpression
      of CD80 was observed. We have previously observed that human thymic B cells are
      surrounded by rosetting thymocytes; a relationship which is maintained when cells
      are cultured. Here we show that the rosettes are remarkably stable in both man
      and mouse. They are dependent on intact surface protein but not on divalent
      cations, active metabolism, or components of the cytoskeleton. The rosettes could
      not be dissociated with antibodies to CD40 or CD80. Failure to consider such a
      stable rosette structure would result in sampling biases when purifying thymic B
      cell populations and could also contribute to some of the more unusual phenotypic
      findings such as the expression of CD2.

PMID- 7522129
TI  - Differential expression of adhesion and homing molecules by human decidual and
      peripheral blood lymphocytes in early pregnancy.
AB  - Decidual and peripheral blood lymphocyte subsets were studied for their
      expression of CD44, L-selectin (Leu-8), CD54, and CD11b cell adhesion molecules
      (CAM). Most CD3+, CD4+, CD8+, and CD56+ cells in decidua were L-selectin- and
      CD44+, i.e., had a phenotype consistent with mucosa-homing preference of decidual
      lymphocytes (DL). We observed trimodal staining of decidual and peripheral blood
      CD56+ and CD8+ cells with anti-CD44 monoclonal antibody; negative, weakly
      positive, and brightly positive subpopulations were evident. Relatively high
      levels of CD44-negative CD56+ and CD8+ cells were found in decidua. Most decidual
      T and natural killer (NK) cells expressed high amounts of the CD54 molecule.
      Substantially higher numbers of CD3+, CD4+, and CD8+ cells in decidua bore CD11b,
      whereas the percentage of CD11b-positive NK cells was significantly lower in
      decidua, compared with that seen in peripheral blood. As opposed to peripheral
      blood lymphocytes (PBL), phorbol 12-myristate 13-acetate (PMA) stimulation of
      decidual NK cells elicited a rapid increase in the numbers of CD11b-positive
      cells but not increased fluorescence intensity of CD11b on the stained cells. The
      CD54 molecule was also up-regulated on decidual and peripheral blood NK cells but
      only after 15 hr of stimulation with PMA. In contrast to peripheral blood cells,
      activation of decidual mononuclear cells by K562 did not lead to an augmentation
      of the CD11b and CD54 expression on NK lymphocytes. These findings suggest that
      expression of CAM on DL is regulated in a manner different from that of PBL, and
      CAM expression may be adapted to accommodate placentation in human beings. The
      interaction of lymphocytes by means of antigen-independent cell-cell adhesion
      could be essential for the development of the placenta and the regulation of the
      local maternal immune response to the genetically foreign fetus.

PMID- 7522128
TI  - Requirements for stimulation or anergy induction in alloreactive human T cell
      clones.
AB  - The "two signal" concept for T cell activation is widely accepted. Signal 1 is
      commonly delivered via the antigen receptor, and signal 2 via accessory
      interactions. Delivery of both signals results in activation, signal 1 alone in
      induction of hyporesponsiveness. The nature of signal 1 in alloreactivity is not
      completely clear; most evidence suggests that a complex of foreign major
      histocompatibility complex molecules and their bound peptides is recognized.
      Interactions between B7 (CD80) ligand and CD28/CTLA-4 receptors are currently
      considered the most important sources of signal 2. Xenogeneic cells transfected
      with human genes provide useful stimulators for dissecting signals 1 and 2 in
      alloreactivity. We show here that the majority of DR-specific alloreactive T cell
      clones (TCC) fails to recognize Chinese hamster ovary (CHO) cells transfected
      with human DR, whether or not these are cotransfected with genes for CD80 or LFA
      3. Stimulation was not observed even in the presence of a pool of peptides
      isolated by low pH release from B cell line (BCL)-derived DR molecules, or in the
      presence of synthetic peptides corresponding to the sequences of the three most
      commonly identified endogenous peptides. Lack of recognition was observed both in
      failure to stimulate proliferation and in failure to induce anergy. However, one
      TCC was identified which responded weakly to DR+ CHO cells, and for this clone,
      the presence of either CD80 or LFA-3 strongly enhanced proliferative responses.
      Anergy was not induced, even in the absence of CD80. Immobilized HLA-DR molecules
      purified from a BCL also failed to stimulate proliferation, but unlike the CHO
      transfectants, they did induce anergy. Stimulation with BCL also induced anergy
      if CD80-dependent interactions were blocked with soluble CTLA-4-Ig receptor.
      These results are consistent with the model that DR molecules expressed in the
      absence of appropriate peptide are simply not recognized by most alloreactive T
      cells, whereas DR molecules containing appropriate bound peptide are recognized
      as signal 1 and induce anergy. CTLA-4-Ig blocking confirms that CD80-dependent
      interactions can be important in preventing anergy induction, but that they are
      not always necessary is illustrated by the existence of a single clone which
      recognized DR molecules on CHO transfectants, giving very weak proliferation
      without CD80, and nonetheless no anergy induction.

PMID- 7522131
TI  - Characterization of keratin densities in mitotic WISH cells.
AB  - Three dimensional (3-D) reconstruction of four mitotic WISH cells from ultrathin
      sections gave an informative representation of the spatial distribution of
      keratin densities in these cells. The correspondence between the densities as
      studied by transmission electron microscopy (TEM) and the keratin bodies
      initially revealed by immunoflourescent colabeling of cultures, was confirmed by
      immunoelectronmicroscopy. The smaller, and sometimes more elongated densities,
      were relatively abundant just beneath the subplasmalemmal microfilament band; and
      at certain levels of the mitotic cell they were observed to be connected to
      neighboring densities by intact intermediate filaments (IFs). The larger and more
      spherical densities appeared to be somewhat more discrete and randomly
      distributed. Other observed associations of the keratin densities included the
      telophase contractile ring of microfilaments, chromosomes, the reformed telophase
      nucleus, and desmosomal junctions with neighboring interphase cells. Cytochalasin
      D (CD) treatment of cells displaced the peripheral keratin densities toward the
      cell membrane. The density volume constituted 0.52% to 1.57% of the total cell
      volume, and the proportional density size was decreased in the cells that had
      progressed into anaphase and telophase. The observed formation and subsequent
      dissolution of keratin densities during mitosis may represent a dynamic mechanism
      of restructuring the keratin cytoskeleton in an unpolymerized form in order to
      allow for rapid reformation of interphase cell junctions. The physical
      associations observed between intact IFs and the keratin densities may provide
      support at certain depths of the mitotic cell, and the juxtaposition of densities
      with nuclear components suggests a possible source of and role for keratin IFs
      during nuclear events.

PMID- 7522130
TI  - FK506 and cyclosporin A each inhibit antigen-specific signaling in the T cell
      line 171 in the absence of a calcium signal.
AB  - Antigen-specific signal transduction leading to IL2 induction and secretion in
      the T cell line 171 is augmented by association of p56lck with CD4. Although no
      change in cytoplasmic calcium level ([Ca2+]i) was detectable during antigen
      specific signal transduction of 171-CD4+ cells, IL2 induction was inhibited by
      FK506 and CsA. Since these drugs are thought to act selectively by inhibiting
      calcineurin, a calcium-calmodulin-dependent protein phosphatase associated with
      activation of the IL2 promoter, we considered the possibility that calcineurin is
      constitutively active in 171 cells. However, we found no evidence for this
      because PMA failed to supplement any putatively active calcineurin to induce IL2
      secretion. We suggest that IL2 secretion induced by antigen presentation to
      TCR/CD4/p56lck requires an FK506 and cyclosporin A-sensitive step which may be
      independent of calcium signaling. Rapamycin did not inhibit IL2 secretion induced
      by TCR/CD4/p56lck, emphasizing the specific action of FK506 and cyclosporin A.

PMID- 7522134
TI  - Focal mechanisms underlying ventricular tachycardia during prolonged ischemic
      cardiomyopathy.
AB  - BACKGROUND: The present study was performed to define the mechanisms underlying
      spontaneously occurring ventricular arrhythmias in the failing heart. METHODS AND
      RESULTS: Three-dimensional cardiac mapping from as many as 232 intramural sites
      was performed in five dogs with ischemic cardiomyopathy induced by multiple
      intracoronary embolizations. After 5 to 10 weekly embolizations with 90-microns
      latex microspheres into the left anterior and circumflex coronary arteries, left
      ventricular ejection fraction decreased from 63 +/- 3% to 22 +/- 3%. Subsequent
      weekly Holter monitoring of dogs in the conscious state demonstrated frequent
      multiform premature ventricular complexes (PVCs) (< or = 2000/d), couplets, and
      runs of ventricular tachycardia (VT) (< or = 70 beats in duration and < or = 560
      beats per minute) in all dogs. Three-dimensional mapping of spontaneous rhythm
      for 60 minutes was performed an average of 6.4 weeks after the last embolization,
      during which time each dog demonstrated multiform PVCs, couplets, and runs of
      nonsustained VT at rates comparable to those in the conscious state. Mapping was
      of sufficient density to define the mechanism for 31 PVCs, 45 beats of
      ventricular couplets, and 99 beats of VT. Sinus beats preceding PVCs (n = 36)
      initiated in the septum and spread rapidly with a total activation time (46 +/- 1
      milliseconds) that did not differ from that of sinus beats not preceding PVCs or
      VT (46 +/- 2 milliseconds, n = 10, P = .69). PVCs and the first beat of couplets
      or VT were initiated primarily in the subendocardium by a focal mechanism, based
      on the lack of intervening electrical activity between the termination of the
      preceding (sinus) beat and initiation of the ectopic beat (225 +/- 23
      milliseconds), despite the presence of multiple intervening intramural recording
      sites. All subsequent beats of VT also were initiated by a focal mechanism, and
      their total activation time (89 +/- 1 milliseconds) did not differ from that of
      the initiating ectopic beats (86 +/- 2 milliseconds, P = .14), despite
      acceleration of VT to a cycle length of 200 milliseconds. Monomorphic VT was due
      to repetitive focal activation of subendocardial sites. Polymorphic VT was due to
      sequential focal activation from multiple sites arising in the subendocardium
      and, at times, in the subepicardium. Comparison of mapping data with results of
      detailed anatomic analysis of tissue demonstrated that focal sites of initiation
      exhibited patchy nontransmural fibrosis. Functional conduction delay of a
      moderate degree was evident only when fibrosis extended transmurally.
      CONCLUSIONS: Spontaneously occurring PVCs, couplets, and VT in a model of
      ischemic cardiomyopathy are initiated and maintained by focal mechanisms with no
      evidence of macroreentry. Thus, therapeutic regimens to treat or prevent VT in
      the presence of ischemic cardiomyopathy will likely require interruption of these
      focal mechanisms.

PMID- 7522133
TI  - Decrease in myocardial ryanodine receptors and altered excitation-contraction
      coupling early in the development of heart failure.
AB  - BACKGROUND: Rapid ventricular pacing for 1 day reduced myocardial contractile
      function without inducing heart failure in conscious, chronically instrumented
      dogs. After 4 to 7 weeks of pacing, myocardial contractility was depressed
      further and overt signs of congestive heart failure, eg, ascites, dyspnea, and
      edema, were evident. METHODS AND RESULTS: The mechanical restitution response, a
      physiological index of calcium release, was depressed at 1 day of rapid
      ventricular pacing. Postextrasystolic potentiation was also depressed by a
      similar amount, 14 +/- 3%, at 1 day after pacing. The response to isoproterenol
      0.2 microgram/kg per minute was depressed by a significantly greater amount (P <
      .05), 52 +/- 7%, at 1 day after pacing. 3H-ryanodine receptor binding fell from
      1013 +/- 25 to 808 +/- 42 fmol/mg after 1 day of pacing and remained depressed at
      similar levels (782 +/- 61 fmol/mg) at 4 to 7 weeks when heart failure was
      manifest. Ryanodine receptor affinity was unchanged from control values. Neither
      dihydropyridine binding nor affinity for 3H-PN200-110 was changed from control
      levels. Within 5 days after recovery from 1 day of pacing, physiological
      responses to isoproterenol, postextrasystolic potentiation, and mechanical
      restitution recovered, as did 3H-ryanodine binding density. CONCLUSIONS: These
      findings suggest that the changes in excitation-contraction coupling and
      potentially the sarcoplasmic reticulum calcium release channel occur early in the
      development of heart failure and therefore may be important in the pathogenesis
      of the contractile abnormalities in this disease state.

PMID- 7522132
TI  - Platelet alpha-granule release in cocaine users.
AB  - BACKGROUND: Cocaine use has been associated with arterial occlusion resulting
      from platelet-rich thrombi and with an accelerated, often atypical
      atherosclerotic lesion that could be ascribed to platelet activation and platelet
      alpha-granule release. METHODS AND RESULTS: Using a flow cytometric method to
      quantitate the percent of circulating activated platelets in whole blood (those
      that express the alpha-granule membrane protein P-selectin), we found that 5 of
      25 samples from 12 long-term cocaine users had a baseline level of circulating
      activated platelets > 3 SD (range, 19% to 60%) above the mean (4.4 +/- 3.7%, mean
      +/- 1 SD) for 85 nonusers (sample n = 130). This subset resulted in a
      significantly higher mean baseline level of circulating activated platelets (11.8
      +/- 14.4%) for all cocaine users (P = .01). By contrast, cocaine and its
      metabolites, at concentrations documented as obtainable during in vivo cocaine
      use (10(-7) to 10(-5) mol/L), had no effect on in vitro platelet activation or
      aggregation, either directly or in concert with platelet agonists. However, in
      experiments in which cocaine users received blinded infusions of placebo or
      cocaine, the mean percent of circulating activated platelets rose significantly
      (P < .05) after infusion of either placebo (peak 77 +/- 31%) or cocaine (peak 65
      +/- 28%), the latter at doses resulting in peak plasma cocaine levels averaging <
      10(-6) mol/L. CONCLUSIONS: Long-term cocaine use in some subjects is
      intermittently associated with high basal levels of circulating platelets that
      have undergone alpha-granule release. The inability of cocaine and its
      metabolites at concentrations of 10(-7) to 10(-5) mol/L to cause platelet P
      selectin expression in vitro in this study, coupled with the acute increase in
      circulating activated platelets observed in vivo after either cocaine or placebo
      infusion, suggests that in vivo platelet alpha-granule release associated with
      cocaine use may occur through indirect rather than direct effects of the drug.

PMID- 7522136
TI  - SR1 assays of alpha-fetoprotein, carcinoembryonic antigen, and prostate-specific
      antigen compared with corresponding established commercial assays.
AB  - We compared results obtained with the newly developed alpha-fetoprotein (AFP),
      carcinoembryonic antigen (CEA), and prostate-specific antigen (PSA) assays for
      the fully-automated Serono SR1 analyzer with those obtained with the major,
      established methods for these analytes: Serono Serozyme and Bridge, Abbott IMx,
      Kodak Amerlite, Boehringer Mannheim ES600, Pharmacia Delfia, Hybritech Tandem-E
      and Tandem-R, Ciba Corning ACS180, and DPC IRMA-Count. The correlations were good
      for all methods studied (r > or = 0.94). For AFP, numerical agreement was good,
      with linear regression slopes of 0.88 to 1.15; for CEA, correlation slopes of
      1.03 to 1.16 were observed. The SR1 PSA assay agreed well with five of the seven
      methods studied (slopes of 0.98 to 1.22), but the Ciba Corning ACS180 PSA assay
      gave results higher than all other methods studied (slope 0.54 vs SR1 at low
      doses) and the Abbott IMx PSA assay gave results lower than all other methods
      studied (slope 1.47 vs SR1).

PMID- 7522138
TI  - False-negative urinary pregnancy test in a woman with a combined pancreas-kidney
      transplant.

PMID- 7522137
TI  - Simultaneous macroamylasemia and macrolipasemia.
AB  - The first case of the simultaneous presence of macroamylasemia and macrolipasemia
      in a patient with gluten enteropathy (celiac disease) is described. Both
      macroenzymes were formed by association of polyclonal IgA with amylase and
      lipase. Both macroenzymes had molecular masses > 300 kDa.

PMID- 7522139
TI  - Electrophysiologic characteristics at initiation of ventricular tachycardia and
      ventricular fibrillation in a canine infarct model.
AB  - Local ventricular activation time and the conduction time during sinus rhythm at
      the induction of ventricular tachycardia (VT) and ventricular fibrillation (VF)
      were investigated using a canine model of chronic myocardial infarction. Of 26
      dogs studied, 15 had inducible VT, 10 had inducible VF, and 1 had no inducible
      arrhythmias. Bipolar local ventricular electrograms were recorded during sinus
      rhythm from 136 sites in 10 dogs with VT and 164 sites in 11 dogs with VF. Mean
      activation time in dogs with inducible VT was significantly longer than in dogs
      with inducible VF. Furthermore, simultaneous local ventricular electrograms were
      recorded during the induction of VT (74 episodes) or VF (38 episodes) from the
      infarct border zone at the endocardium (B-EN), the epicardium (B-EP), and normal
      sites (N-EN, N-EP). During VT induction, the activation time at N-EN and N-EP was
      significantly longer than during VF induction (N-EN: 94 +/- 21, 70 +/- 19 ms; N
      EP: 83 +/- 21, 64 +/- 10 ms; p < 0.05). Conduction time was measured at the
      initiation of VT or VF induced by orthodromic or antidromic pacing. The
      conduction times of the last paced beat between N-EN and B-EP (35 +/- 11, 62 +/-
      24 ms), N-EN and N-EP (35 +/- 12, 14 +/- 13 ms), B-EN and B-EP (16 +/- 10, 38 +/-
      25 ms), and B-EP and N-EP (77 +/- 27, 44 +/- 12 ms) were significantly different
      in dogs with inducible VT (p < 0.05), but not in dogs with VF.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7522135
TI  - Identification of myocardial reperfusion with echo planar magnetic resonance
      imaging. Discrimination between occlusive and reperfused infarctions.
AB  - BACKGROUND: The current treatment of many cases of acute myocardial infarction
      involves the use of thrombolytic agents. Evaluation of this therapy requires
      determination of the success of reperfusion and assessment of the presence and
      extent of infarction in the reperfused territory. The present study was designed
      to simulate in rat models several possible outcomes of reperfusion therapy: (1)
      successful reperfusion and absence of myocardial infarction, (2) successful
      reperfusion and presence of myocardial infarction, and (3) unsuccessful
      reperfusion. The usefulness of contrast-enhanced fast magnetic resonance (MR)
      imaging in defining the success of reperfusion was investigated. The dynamic
      effects were examined of low and high doses of gadolinium-BOPTA/dimeglumine (Gd
      BOPTA/dimeg) on myocardial signal using MR inversion recovery echo planar imaging
      (IR-EPI) and gradient recalled echo planar imaging (GR-EPI), respectively.
      METHODS AND RESULTS: Rats were subjected to one of the following regimens:
      reperfused reversible myocardial injury (n = 9), reperfused irreversible
      myocardial injury (n = 9), and occlusive infarction (n = 9). MR echo planar
      images were acquired every 1 or 2 seconds before, during, and after
      administration of Gd-BOPTA/dimeg. In all groups, normal myocardial signal was
      sharply increased on IR-EPI and decreased on GR-EPI at the peak of the bolus,
      followed by a gradual decline to baseline. In animals subjected to reperfused
      reversible myocardial injury, normal and previously ischemic regions were
      indistinguishable during and after the passage of Gd-BOPTA/dimeg. On the other
      hand, enhancement of reperfused irreversibly injured myocardium was delayed but
      increased steadily to a higher level than normal myocardium on IR-EPI. The
      reperfused irreversibly injured myocardium was identified on IR-EPI as a zone of
      high signal (hot spot). On GR-EPI, signal loss in reperfused irreversibly injured
      myocardium was significantly less compared with normally perfused myocardium. In
      animals with occlusive infarctions, there was no change in signal intensity over
      the ischemic region on either IR-EPI or GR-EPI. Occlusive infarction was
      identified as zones of either low (cold spot) or high (hot spot) signal compared
      with normal myocardium, depending on MR pulse sequence and dose of the contrast
      medium. CONCLUSIONS: The transit of Gd-BOPTA/dimeg monitored by fast MR imaging
      techniques can be used to distinguish between reperfused reversibly and
      reperfused irreversibly injured myocardium and between occlusive and reperfused
      infarctions.

PMID- 7522140
TI  - Isolated capillary proliferation in Leigh's syndrome.
AB  - An infant with hypotonia and recurrent apneic spells died with a diagnosis of
      pyruvate dehydrogenase deficiency and showed typical pathological changes of
      Leigh's syndrome at postmortem. Despite the prominence of symptoms suggesting
      dysfunction of brainstem respiratory centers during life, lesions were not found
      in the upper medulla. However, quantitative morphometric analysis demonstrated
      abnormal capillary hyperplasia in the region including and between the nucleus
      ambiguus and nucleus tractus solitarius. There was an average area of 8.0 +/- 2.5
      x 10(6) mm2 occupied by capillaries per 0.75 mm2 field in the patient's
      brainstem, compared with 4.6 +/- 1.6 x 10(6) mm2 and 5.5 +/- 1.4 x 10(6) mm2 in
      two age-matched controls (p < 0.01). We speculate that capillary hyperplasia is a
      pathological marker of chronically impaired oxidative metabolism in the central
      nervous system in metabolic disease.

PMID- 7522142
TI  - Detection of antigen-specific immune complexes in sera of gastric and esophageal
      cancer patients.
AB  - Using the murine monoclonal antibodies against human gastric cancer cell antigens
      designated MG7 and MGd1, we developed a sandwich ELISA to detect the levels of
      antigen-specific immune complexes (IC) in human sera. By this assay, only
      6.7%(6/90) of healthy blood donors and 9.2%(6/65) of patients with chronic
      gastritis had antigen-specific IC in sera exceeding the cut-off value. Whereas
      21.4%(6/28) of patients with colorectal cancer, 18.2%(4/22) of patients with
      hepatocellular cancer, 11.4%(4/35) of patients with lung cancer and 9.5%(2/21) of
      patients with breast cancer had elevated levels of the antigen-specific IC. In
      contrast, 58.7%(54/92) of patients with gastric cancer and 53.3%(24/45) of
      patients with esophageal cancer were positive for this antigen-specific IC.
      Determination of levels of antigen-specific IC in sera may be useful in serologic
      diagnosis of patients with gastric and esophageal cancer.

PMID- 7522141
TI  - Prevalence of arrhythmias in patients with idiopathic dilated cardiomyopathy.
AB  - A total of 105 patients with idiopathic dilated cardiomyopathy (IDCM) underwent
      Holter monitoring. The prevalence of arrhythmias was as follows: ventricular
      premature beats (VPB) 100%, including complex VPB 58.1%, short runs of
      ventricular tachycardia (VT) 25.7%, A-VB or BBB 46.7%, atrial arrhythmias 38.1%,
      sinus node dysfunction 6.6%, ST-T change 38.1%. The incidence of ventricular
      arrhythmia (VA) was not related to severity of cardiac dysfunction (NYHA),
      duration of illness and sex. The most common arrhythmia was VA, the second one
      was heart block and atrial arrhythmia. Serum norepinephrine and epinephrine
      levels were 743.4 +/- 252.5 and 688.0 +/- 452.4 pg/ml, respectively, which were
      higher than those in control group (P < 0.01). Isoproterenol sensitivity test
      (ICD25) 8.43 +/- 11.21 micrograms, was also much higher than that in control
      group (P < 0.01). Average H-V interval was 69.4 +/- 13.3 msec in HBE. Eight
      patients died. Two died of congestive heart failure (class II-IV), and six cases
      were diagnosed as sudden cardiac death resulting from VT and VF.

PMID- 7522144
TI  - Background EEG activity in preterm infants: correlation of outcome with selected
      maturational features.
AB  - The aim of this study is to identify normal EEG patterns of preterm infants,
      characteristic of early postmenstrual ages (PMAs). Quantitative features of EEG
      background activity have been examined in records from 83 preterm infants within
      the first 2 weeks of life at a PMA of 27-34 weeks. These subjects presented
      different cranial ultrasound findings and different outcomes. EEG quantitative
      data have been compared to the subsequent neurological evolution. We supposed
      that the features of EEG background activity which were associated with a
      favourable outcome should be considered as indexes of "normality" of the tracing
      for that specific PMA. At 27-30 weeks of PMA a high incidence of "temporal
      sawtooth," a particular rhythmic theta activity detectable in temporal regions,
      relates to a favourable evolution, therefore it can be assumed that this activity
      is a normal feature of EEG tracings at this age. On the contrary, a significant
      correlation between a high incidence of "temporal sawtooth" and an abnormal
      outcome is observable at 33-34 weeks and leads us to deduce that this pattern
      should disappear at this time. After 31 weeks other parameters (such as the
      incidence of 8-20 Hz activities, the length of the intervals and burst duration)
      show a significant correlation with the outcome.

PMID- 7522143
TI  - [Pain therapy of tumor patients with special reference to tumors of the
      gastrointestinal tract. WHO staged schedule versus para-spinal analgesia
      techniques].
AB  - In this study we compared 293 patients with cancer pain undergoing treatment in
      the years 1987 until 1993. 165 patients (55.7%) suffering from cancer localized
      at the organs of gastrointestinal tract. Comparing the therapeutic results of WHO
      pattern with patients after implantation of port systems with epidural or
      intrathecal catheters and portable external morphine pumps we found at port
      patients a significant lower number of side effects like nausea, vomiting,
      obstipation and weariness. Furthermore we noted at port-patients lower values of
      pain score (VAS). We think the high incidence of uncomfortable side effects of
      drugs at patients with gastrointestinal cancer may be caused by the type of
      special illness. Therefore we discuss the possibility of an earlier use of the
      method of port implantation at special indications.

PMID- 7522145
TI  - Neurophysiology and SPECT cerebral blood flow patterns in dementia.
AB  - A series of elderly patients with dementia of Alzheimer type (AD), multi-infarct
      dementia (MID) and functional (non-organic) psychiatric illness (major depressive
      disorder) were selected by DSM III-R criteria and had the following
      investigations: a battery of cognitive tests, EEG with power and coherence
      spectral analyses of T4-T6, T3-T5, P4-O2, P3-O1 channels, visual evoked potential
      (flash and pattern reversal) and P300 recordings as well as single photon
      emission tomography (SPECT) using 99mTc HMPAO. Three subsets of patients were
      chosen on clinical and SPECT criteria. These were as follows: patients with a
      clinical diagnosis of AD and a SPECT rCBF pattern showing bilateral temporo
      parietal perfusion deficits (AD type), patients with a clinical diagnosis of MID
      and a SPECT rCBF pattern showing single focal perfusion deficits or multiple
      areas of low perfusion in the cerebral cortex suggestive of ischaemic change (MID
      type SPECT picture) and functionally ill patients with normal rCBF (controls).
      The AD type group differed from the MID rCBF group in having significantly less
      alpha and more delta 2 (2- < 4 Hz) power. The latter had significantly lower
      alpha power than the controls. The 2 dementia groups with abnormal rCBF patterns
      did not differ in terms of coherence spectra or P300 latencies, but both had
      lower within and between hemisphere alpha coherence values and longer P300
      latencies than the "controls" with normal rCBF. There were no group differences
      in the flash VEP P2-pattern reversal P100 latency difference values.

PMID- 7522146
TI  - Comparisons of MEG, EEG, and ECoG source localization in neocortical partial
      epilepsy in humans.
AB  - In order to delineate the characteristics of epileptic spikes, 1946 different
      spikes were studied in 6 patients with complex partial epilepsy. Non-invasive MEG
      and EEG source analysis of interictal spikes were contrasted to ECoG
      localization, surgical outcome and presence of lesions on MRI. Results indicated
      that: (1) using the most frequent occurring spike topography patterns from a
      large sample of spikes improved goodness-of-fit values for both MEG and EEG
      localization, (2) when spike patterns could be appropriately matched on several
      successive MEG measurements to provide an adequate matrix (3 of 6 subjects),
      there was excellent agreement between MEG dipole sources and ECoG sources as well
      as surgical outcome and presence of MRI lesions, (3) EEG source analyses also
      gave good results but not as consistently as MEG.

PMID- 7522147
TI  - Functional anatomy of the human supplementary sensorimotor area: results of
      extraoperative electrical stimulation.
AB  - Electrical stimulation studies have demonstrated that a "supplementary motor
      area" (SMA) exists in humans. However, its precise functional organization has
      not been well defined. We reviewed the extraoperative electrical stimulation
      studies of 15 patients with intractable epilepsy who were evaluated with
      chronically implanted interhemispheric subdural electrodes. SMA-type positive
      motor responses were elicited not only from the mesial portion of the superior
      frontal gyrus but also from its dorsal convexity, and from the paracentral
      lobule, cingulate gyrus, and precuneus. Sensory symptoms, that could not be
      attributed to stimulation of the primary sensory area, were elicited from the
      superior frontal and cingulate gyri in addition to the precuneus. Therefore,
      human SMA, as defined by electrical stimulation, is not always confined to the
      mesial portion of the superior frontal gyrus as described previously. It is also
      not strictly "motor" but "sensorimotor" in representation. We propose referring
      to this region as the "supplementary sensorimotor area" (SSMA). We observed a
      somatotopic organization within the SSMA with an order of lower extremity, upper
      extremity, and head from posterior to anterior. Sensory representation in an
      individual was either anterior or posterior to the positive motor representation
      but never both. There was a supplementary eye field within the head
      representation. A supplementary negative motor area was noted at the anterior
      aspect of the SSMA. No language area was demonstrated within the SSMA. The
      physiologic significance of the SSMA and functional consequences of its resection
      must be addressed in further studies.

PMID- 7522150
TI  - Differential effects of extended sleep in narcoleptic patients.
AB  - The aim of the present study was to investigate the effects of extended night
      sleep on subsequent daytime sleep propensity in narcoleptic patients. The
      possible differentiation between REM and NREM sleepiness was of particular
      interest. Ten unmedicated narcoleptic inpatients (8 men, 2 women) aged 23-61
      years (mean, 47.9 years) participated in this study. Adapting the patients to the
      hospital schedule (nocturnal sleep period from 22:00 to 6:00 h and ad lib, nap
      during daytime) for at least 2 weeks, we conducted a baseline PSG from 22:00 to
      6:00 h and subsequent 5-trial daytime sleep recordings with naps (lying on the
      bed for 20 min light-out period) at 9:30, 11:30, 13:30, 15:30 and 17:30 h (the
      baseline condition: BC). After a 1-5 day interval, we conducted an extended PSG
      from 22:00 to 10:00 h. Subsequent to the extended PSG, we carried out 5-trial
      daytime sleep recordings. We adjusted the start time of the first nap trial at
      least 90 min after waking time and start time in the 5th nap trial before 19:00 h
      (the extended condition: EC). Mean TST was 417.0 min in the baseline PSG, and
      595.2 min in extended PSG. Mean number of daytime naps per subject exhibiting a
      sleep latency shorter than 10 min was decreased in EC. Mean sleep latency in EC
      was significantly prolonged in comparison with that in BC. This prolongation of
      mean sleep latency per subject was positively correlated with S4 duration and %
      S4 obtained in the morning of the extended PSG (from 6:00 to wake time).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7522149
TI  - Spectrum of EEG abnormalities during clozapine treatment.
AB  - Clozapine is a novel antipsychotic agent effective in treating refractory
      schizophrenia. Clozapine produces fewer extrapyramidal effects than other
      neuroleptics, although agranulocytosis and seizures are significant adverse
      effects. To characterize the spectrum of clozapine-related
      electroencephalographic abnormalities, we identified 10 patients who had
      electroencephalograms (EEGs) performed before and during clozapine treatment.
      These 10 patients represented a subset of individuals participating in an
      investigational trial. During clozapine treatment, five developed myoclonus and
      one experienced a generalized tonic-clonic seizure. Records were retrospectively
      reviewed by an electroencephalographer blinded to the patient's history and
      medications. All patients had normal EEGs before clozapine treatment. While
      receiving clozapine (250-900 mg daily), all patients developed background slowing
      in the theta and often delta ranges. Additionally, 7 patients exhibited bilateral
      spike, polyspike and slow wave discharges, one with a photoparoxysmal response.
      Follow-up EEGs performed in 4 of these 7 patients after a decrease in clozapine
      dosage and/or addition in valproic acid showed diminished epileptiform activity.

PMID- 7522148
TI  - Practical detection of epileptiform discharges (EDs) in the EEG using an
      artificial neural network: a comparison of raw and parameterized EEG data.
AB  - We have developed and tested "off-line" an artificial neural network (ANN) that
      successfully detects epileptiform discharges (EDs) when trained on EEG records
      marked by an electroencephalographer (EEGer). The system was trained on both
      parameterized and raw EEG data and can process 49 channels of EEG data in real
      time on an 80486/33 MHz personal computer, making it capable of processing EEG on
      line in long-term monitoring units. Our detector consists of 2 stages: (1) a
      threshold detector identifies candidate EDs in 4-channel bipolar chains within
      the recording montage, parameterizes them and then passes these data to the
      second stage; (2) a 3-layer feed-forward ANN decides if a candidate wave form is
      an ED. The intersection of detector sensitivity and selectivity curves, or
      crossover threshold, for 10 patients from our Epilepsy Monitoring Unit occurred
      at 73% for parameterized EEG data and at 46% for "raw" EEG data. The ANN could be
      adapted to different EEGers' styles by changing the ANN output threshold for
      accepting candidate wave forms as EDs. In this "proof of principle" study the
      detector was trained on EEGs from 10 Johns Hopkins Hospital Epilepsy Monitoring
      Unit (JHH EMU) patients. We used different EEGs from the same patients for
      testing. Current testing should demonstrate that the ANN detector can generalize
      to previously "unseen" patients. This study shows that ANNs offer a practical
      solution for automated, real time ED detection that uses, standard, inexpensive
      computers, is easily adjustable to individual EEGer style and can produce
      sensitivities and selectivities similar to those of EEGers.

PMID- 7522151
TI  - The presaccadic cortical negativity prior to self-paced saccades with and without
      visual guidance.
AB  - The presaccadic negativity (PSN) of the scalp EEG potential prior to self
      initiated saccades aimed either at a visual target or at the remembered position
      of that target in total darkness was analysed in 10 normal subjects. Under both
      conditions a PSN with a negligible EOG contamination was found, showing 4
      characteristics: (1) In both conditions, the PSN maximum is localized at the
      vertex, probably containing the activity of the supplementary motor area. (2) At
      an electrode placed over the frontal eye field (FEF) contralateral to the saccade
      direction, there is a temporary, circumscribed maximum prior to saccades to the
      visual target, thus probably reflecting activity of the FEF. (3) Prior to
      saccades to the visual target, there is a statistically significant
      interhemispheric difference of the PSN over the parietal cortex with a larger
      amplitude over the hemisphere contralateral to the saccade direction; this might
      be attributed to directed visual attention. (4) Prior to saccades without visual
      guidance in darkness there is a statistically significant interhemispheric
      difference of the PSN over the frontal cortex with a larger amplitude over the
      hemisphere contralateral to the saccade direction. The amplitude of the PSN
      decreased in the course of the experiment, probably due to psychological factors
      such as attention and motivation. Our results suggest that the PSN is a readiness
      potential preceding voluntary saccades, containing activity related both to
      unspecific psychological processes and to specific movement preparation in the
      frontal and parietal ocular motor areas.

PMID- 7522152
TI  - The results of computer-assisted ambulatory 16-channel EEG.
AB  - The objective of this study was to examine the results of 16-channel computer
      assisted outpatient long-term EEG monitoring (CO-LTM) and to compare those
      results to previously published reports using 4- and 8-channel ambulatory
      cassette-based continuous recordings. Patients were referred to a community-based
      outpatient EEG service for further diagnostic evaluation using this 16-channel
      bipolar recording system. 344 patients were recorded for an average of 1.4 days.
      EEG was reviewed for the presence of patient identified events, computer
      identified interictal and ictal abnormalities, and periodic time samples. A push
      button recording that signified a clinical event was obtained in 166 patients
      (48.3%); 41 (11.9%) of these recordings included a seizure and 125 (36.3%) showed
      no EEG changes during the habitual event. An EEG abnormality was identified by
      the computer in an additional 90 recordings (26.2%), for an overall clinical
      usefulness of 74.4%. Among the 191 patients referred with previously normal
      routine EEGs, a total of 129 (67.5%) of these recordings were useful. 48 (25.1%)
      of these tracings were abnormal and an additional 81 push-button events (42.4%)
      showing no changes from background EEG were recorded. In conclusion, computer
      assisted outpatient EEG monitoring provides good success rates for clinically
      useful information.

PMID- 7522153
TI  - EEG coherence in Alzheimer disease, by Besthorn et al.

PMID- 7522154
TI  - Differences in responsiveness to CD3 stimulation between naive and memory CD4+ T
      cells cannot be overcome by CD28 costimulation.
AB  - Activation of naive CD4+ T cells is essential for the induction of primary immune
      responses. However, this subset is less responsive to signaling via T cell
      receptor/CD3 (TcR/CD3) complex than memory CD4+ cells. For mitogenic activation
      of T cells, in addition to triggering of the TcR/CD3 complex, costimulatory
      signals are required that can be generated by surface structures present on the
      antigen-presenting cells. We investigated here whether differences in
      responsiveness to TcR/CD3 stimulation of naive and memory cells can be overcome
      by the costimulatory pathway B7/CD28. Using a B7-dependent system we show that
      even in the presence of optimal CD28 costimulation, CD4+ naive cells still have
      more stringent TcR/CD3 activation requirements than memory cells. Furthermore,
      titration of the B7 signal revealed that for activation of naive CD4+ cells a
      higher level of cross-linking of CD28 molecules is required than for memory
      cells. Thus, our results show that at least two signals are required for
      activation of both CD4+ memory and naive cells, but that for activation of naive
      cells higher cross-linking of both CD3 and CD28 molecules is necessary.

PMID- 7522155
TI  - Defective lymphokine production by most CD8+ and CD4+ tumor-specific T cell
      clones derived from human melanoma-infiltrating lymphocytes in response to
      autologous tumor cells in vitro.
AB  - Human melanomas are infiltrated by tumor-reactive T lymphocytes. However, the
      ability of these cells to elicit a specific anti-tumor response in vivo remains
      to be established. Because lymphokine production is critical for T cell
      functions, we have analyzed the capacity of melanoma-specific tumor-infiltrating
      lymphocyte (TIL) clones to produce major lymphokines: interleukin-2 (IL-2),
      interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), as well as tumor necrosis
      factor (TNF), in response to direct antigen presentation by autologous and
      allogeneic tumor cells. We report here that, upon stimulation by autologous
      melanoma cells, all TIL clones secreted TNF but only a few of them produced
      significant amounts of IL-2, IL-4 or IFN-gamma. Nonetheless, all these clones
      consistently produced two or three of these last lymphokines upon stimulation
      with phorbol myristate acetate and calcium ionophore, as well as IL-2 upon CD3
      stimulation, showing the existence of three lymphokine profiles among them: Th1,
      Th0 and a profile characterized by IL-2 and IL-4, but not IFN-gamma secretion.
      Stimulation of TIL clones by allogeneic melanoma lines sharing the appropriate
      HLA-peptide complexes revealed that defective IL-2 production seemed to be a
      constant feature for some clones, while it was, for other clones, dependent on
      the antigen-presenting tumor cells. For this last type of clone, we further
      showed that defective IL-2 induction resulted from an LFA-3 defect of some
      melanoma cells or from distinct yet undefined defects of other melanoma lines.
      Our data suggest that defective lymphokine secretion may be an essential
      component of the in vivo failure of melanoma-reactive TIL to control tumor
      development. Interestingly both CD4+ and CD8+ TIL clones from one patient were
      fully activated by the autologous melanoma cells in vitro, supporting a potential
      role of such TIL in spontaneous or induced tumor rejection.

PMID- 7522156
TI  - Identification of collagen and laminin receptor integrins on murine T
      lymphocytes.
AB  - In this study we investigated the receptors by which murine lymphocytes bind to
      collagen and laminin. To identify the collagen and laminin receptors, we
      generated three monoclonal antibodies, two of which (HM alpha 1 and HM alpha 2)
      could inhibit adhesion of activated T cells to collagen and laminin and one of
      which (HM alpha 6) could inhibit that to laminin. Biochemical studies showed that
      the antigens recognized by HM alpha 1, HM alpha 2, and HM alpha 6 are the mouse
      homologues of human VLA-1, VLA-2, and VLA-6, respectively. Finally, we
      demonstrated that both VLA-1 and VLA-2 contribute to the functional interaction
      between collagen and activated T cells, since HM alpha 1 and HM alpha 2
      specifically inhibited collagen-induced TNF secretion from activated T cells.
      These results indicate that VLA-1 and VLA-2 play an important role in regulating
      adhesion and cytokine production of activated T cells.

PMID- 7522158
TI  - Promiscuous T cell recognition of an H-2 IA-presented mycobacterial epitope.
AB  - Genetically permissive T cell epitopes are an important prerequisite for the
      development of peptide-based vaccines or immunodiagnostic reagents. We have
      investigated the structural requirements of permissive T cell recognition of
      peptide p350-369 from the 38-kDa antigen of Mycobacterium tuberculosis. This
      peptide was found to be immunogenic in mice of the H-2b, bm12, d, s and k, but
      not of the H-2f genotype. T cell responses were restricted by I-A class II
      molecules. The same epitope core was recognized in the H-2b, d and k genotypes. T
      cell hybrids from BALB/c and C57BL/10 mice were used to determine: (i) the
      critical residues using substituted peptide derivatives and (ii) the degree of T
      cell promiscuity. Two out of five BALB/c (H-2d)-derived hybridomas tested
      displayed promiscuous peptide recognition in the context of H-2b and H-2bm12
      antigen-presenting cells. The recognition of critical residues was found to be
      uniform for all five hybridomas when tested with syngeneic antigen-presenting
      cells; additional critical residues were identified when the peptide was
      recognized in the context of allogeneic antigen-presenting cells. Only one of the
      four tested C57BL/10 (H-2b) hybridomas showed promiscuity in the context of H
      2bm12. Each of these C57BL/10-derived clones had a distinct response profile
      toward the critical residues. We propose that the demonstrated T cell promiscuity
      involves peptide interaction with polymorphic H-2 I-A residues.

PMID- 7522157
TI  - The two soluble forms of the lipopolysaccharide receptor, CD14: characterization
      and release by normal human monocytes.
AB  - CD14, a glycolipid-anchored membrane glycoprotein, acts as a high affinity
      lipopolysaccharide receptor on leukocytes. We previously reported that the Mono
      Mac-6 cell line releases two different soluble forms of CD14 (sCD14) (Labeta et
      al., Eur. J. Immunol. 1993. 23: 2144). Here we show that the two sCD14, which we
      now refer to as sCD14 alpha (low M(r)) and sCD14 beta (high M(r)), are also
      synthesized and released by normal human monocytes and present in normal plasma.
      Their mechanism of release was examined by using the Mono-Mac-6 cell line,
      chinese hamster ovary cell (CHO)/CD14+ transfectants and plasma from paroxysmal
      nocturnal hemoglobinuria (PNH) patients. It was found that: (1) sCD14 beta is
      released faster than sCD14 alpha and that the release of the latter is a lengthy
      process. (2) Monensin blocked the biosynthesis of membrane-bound CD14 (mCD14) and
      sCD14, additionally, a 50-kDa CD14 polypeptide accumulated in the cell lysate,
      suggesting that the different forms of CD14 may have a common precursor. (3)
      Monensin also blocked the release of sCD14 alpha from surface-labeled cells,
      suggesting that conversion of mCD14 to sCD14 alpha involves a mechanism of
      endocytosis followed by exocytosis. Interestingly, (4) sCD14 alpha and sCD14 beta
      were detected in PNH plasma, indicating that sCD14 alpha may also derive from an
      endogenous pathway. (5) Phospholipase C-released CD14 was identical in size to
      mCD14, thus differed from sCD14 beta by approximately 2000, indicating that
      release of sCD14 beta involves further processing. (6) CHO cells transfected with
      a CD14 cDNA coding for an eight C-terminal amino acids shorter product released
      an sCD14 beta-like form; thus absence of the eight C-terminal amino acids
      prevented mCD14 expression but not the secretion of sCD14 beta. The
      characterization of sCD14 alpha and sCD14 beta reported here may be useful for
      better understanding of variations in sCD14 levels in pathological conditions and
      the contribution of each sCD14 in sepsis and other, as yet unknown functions.

PMID- 7522159
TI  - Mapping of T cell epitopes of the major fraction of rye grass using peripheral
      blood mononuclear cells from atopics and non-atopics. II. Isoallergen clone 5A of
      Lolium perenne group I (Lol p I).
AB  - Rye grass is the major cause of hay fever which currently affects 20% of the
      population. Lolium perenne group I (Lol p I) is a glycoprotein of 240 amino acid
      residues, representing the main allergen of rye grass. We have used peripheral
      blood mononuclear cells (PBMC) from controls and subjects allergic to rye grass
      and cultured them with L. perenne extract (LPE) and Lol p I and measured
      lymphocyte activation using thymidine incorporation. Patients were further
      studied against the 115 overlapping peptides of the iso-allergen clone 5A of Lol
      p I to see whether the 4 amino acid residue differences between clone 1A and
      clone 5A affect the T cell epitope and thus, lymphocyte activation. There are 24
      peptide differences between isoallergen clone 1A and clone 5A occurring in pools
      4, 13, 16 and 19 each one of which could be an immunodominant epitope. The PBMC
      from all allergic patients studied showed a strong proliferative response to LPE
      and Lol p I. Five immunogenic peptide pools, pool 6, 15, 16, 17 and 19 of the
      isoallergen clone 5A were also identified. Most of these pools are in the C
      terminal region of Lol p I. Out of 20 pools tested in vitro 1 pool (pool-17)
      induced PBMC proliferation in five out of six patients who were not restricted to
      an HLA class II DR gene product. However, three out of the six subjects responded
      to various other peptide pools in addition to the immunodominant pool. In spite
      of the amino acid differences between the two clones, pool 17 still remains the
      immunodominant T cell epitope. Control subjects showed only weak responses to LPE
      and no detectable response to either Lol p I or peptide pools. From within the
      most active pool we have defined two peptides of the isoallergen clone 5A
      (identical in sequence with clone 1A) which stimulate lymphocytes from rye grass
      sensitive patients in vitro. Previous studies with the two continuous sequences
      (193WGAVWRIDTPDK204 and 195AVWRIDTPDKLT206) tested in vivo by intradermal skin
      testing have shown typical delayed-type hypersensitivity reactions after 24-48 h
      in one patient. Comparison of amino acid sequences of Lol p I, Lol p II and Lol p
      III proteins revealed a significant level of structural similarity among them.
      Interestingly, 50% of the residues of the second peptide sequence are also
      present in Lol p II and Lol p III.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7522160
TI  - Antigen-driven tissue-specific suppression following oral tolerance: orally
      administered myelin basic protein suppresses proteolipid protein-induced
      experimental autoimmune encephalomyelitis in the SJL mouse.
AB  - Immunomodulatory treatment paradigms have been applied to animal models of T cell
      mediated autoimmune diseases in an attempt to develop an immunospecific and non
      toxic form of therapy which can be applied to humans. These treatment paradigms
      are often directed to T cells with a restricted T cell receptor repertoire or
      that react with dominant peptide determinants. Experimental data, however,
      suggests that even if the initial T cell response is restricted to a specific
      self-protein in the target organ, spreading autoimmunity may develop with
      broadening of T cell autoreactivity to additional epitopes of the same
      autoantigen or to different autoantigens in the target organ. Thus, multiple
      autoantigens may become targets of the autoimmune response. This makes
      immunotherapeutic strategies based on suppressing responses to restricted
      proteins or clones of cells problematic. We have previously shown that
      suppression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat
      by oral myelin basic protein (MBP) is mediated by the release of transforming
      growth factor-beta after triggering by the oral tolerogen. Here, we report that
      in the SJL model of EAE oral administration of an autoantigen from the target
      tissue suppresses disease independent of whether it is or is not the inciting
      antigen. Thus, orally administered MBP or MBP peptides suppress proteolipid
      protein (PLP)-induced EAE, whereas intravenously administered MBP does not. Both
      oral and intravenous PLP, however, suppressed PLP disease. These findings have
      important implications for the use of oral tolerance as a therapeutic approach
      for the treatment of T cell-mediated inflammatory autoimmune diseases in man in
      which the inciting autoantigen is unknown or in which there is autoreactivity to
      multiple autoantigens in the target tissue.

PMID- 7522162
TI  - Autologous cytolytic T lymphocytes recognize a MAGE-1 nonapeptide on melanomas
      expressing HLA-Cw*1601.
AB  - Human melanoma cell line MZ2-MEL expresses several antigens recognized by
      autologous cytolytic T lymphocyte (CTL) clones. We reported previously the
      identification of a gene, named MAGE-1, which codes for antigen MZ2-E which is
      presented by HLA-A1. Gene MAGE-1 is expressed in many tumors of several types but
      not in normal tissues except for testis. We show here that gene MAGE-1 directs
      the expression of another antigen recognized by CTL on the MZ2-MEL cells. This
      antigen, which was named MZ2-Bb, consists of MAGE-1-encoded peptide SAYGEPRKL
      bound to major histocompatibility molecule HLA-Cw*1601. The HLA-Cw*1601 allele
      was found to be expressed by 7 out of 99 individuals from a Caucasian population.
      Our results extend the range of tumor patients who could be eligible for
      immunization against MAGE antigens.

PMID- 7522164
TI  - Inhibition of human IgE synthesis by anti-IgE antibodies requires divalent
      recognition.
AB  - We used a selection of well-characterized murine monoclonal anti-IgE antibodies
      to investigate their effect on human in vitro IgE synthesis. We found anti-IgE
      antibodies that either inhibited or enhanced interleukin-4 plus anti-CD40-induced
      in vitro IgE synthesis in peripheral blood mononuclear cells (PBMC). This
      differential activity was isotype specific as neither IgM nor IgG synthesis were
      affected. Interestingly, only coding IgE mRNA was down-regulated, whereas germ
      line epsilon RNA expression was not influenced by anti-IgE monoclonal antibody
      (mAb). On purified B cells all anti-IgE mAb inhibited interleukin-4 plus anti
      CD40-induced IgE synthesis, implying a role of non-B cells for the enhancing
      activity observed in PBMC. Using Fab and F(ab')2 of an inhibitory anti-IgE mAb we
      could show that divalent recognition was required for inhibition of IgE
      synthesis.

PMID- 7522161
TI  - Major histocompatibility complex class I allele-specific peptide libraries:
      identification of peptides that mimic an H-Y T cell epitope.
AB  - We describe a novel method for screening large libraries of random peptides for T
      cell antigens. Two libraries were constructed, containing fixed amino acids
      representing the major histocompatibility complex (MHC) class I anchor residues
      for H-2Kb-restricted octamers and H-2Db-restricted nonamers. Peptides from the Kb
      restricted library (KbL: SXIXFXXL) and the Db-restricted library (DbL:
      XXXXNXXXIM) specifically stabilize empty Kb and Db molecules, respectively. The
      libraries contain peptides that mimic several H-2b-restricted cytotoxic T
      lymphocyte epitopes, and 21 mimotopes for a Db-restricted H-Y epitope were
      isolated. A degenerate synthetic peptide of limited complexity containing the
      identified H-Y sequence motif was found to be similar to the natural H-Y epitope
      by reverse-phase high performance liquid chromatography analysis. This peptide is
      also capable of immunizing female mice against male splenocytes. Several
      applications for MHC-restricted peptide libraries are discussed.

PMID- 7522163
TI  - Presentation of a horse cytochrome c peptide by multiple H-2b class I major
      histocompatibility complex (MHC) molecules to C57BL/6- and bm1-derived cytotoxic
      T lymphocytes: presence of a single MHC anchor residue may confer efficient
      peptide-specific CTL recognition.
AB  - In this study the immunogenic tryptic fragment from a horse cytochrome c (cyt c)
      digest recognized by cytotoxic T lymphocytes (CTL) induced by in vitro peptide
      stimulation from C57BL/6 (B6) and mutant B6.C-H-2bm1 (bm1) mice is identified. An
      identical sequence, p40-53, is recognized by CTL from both B6 and bm1 mice. In
      addition, both B6 bm1 cloned CTL lines display unusual major histocompatibility
      complex (MHC) class I-restricted recognition of this peptide in that they respond
      to it in the context of H-2Kb, H-2Db, and H-2Kbm1 class I molecules, although the
      sequence lacks the usual structural Kb and Db peptide-binding motifs. Truncated
      analogues which resemble the lengths of naturally processed MHC class I-presented
      peptides, confer reactivity for B6 and bm1 CTL against EL4 (H-2b) targets as well
      as the L cell transfectants, L+Kb, L+Db, and L+Kbm1. The antigenic peptide with
      the greatest potency is p41-49, which appears to be generated by angiotensin
      converting enzyme cleavage of the full-length p40-53 tryptic peptide. The minimum
      antigenic peptide recognized by both B6 and bm1 CTL, and which targets lysis on
      each of the transfectants, is the hexamer p43-48 peptide from horse cyt c.
      Residues Pro44 and Thr47, which occupy polymorphic positions with respect to
      other species-variant cyt c molecules, influence recognition of these peptides
      differently for the B6 and bm1 CTL. The ability of H-2Kb, H-2Db, and mutant H
      2Kbm1 class I molecules to present the same peptide to a single cloned CTL is
      discussed in the context of current knowledge of peptide anchor residues and side
      chain-specific binding pockets in the MHC class I peptide-binding site.

PMID- 7522165
TI  - Interleukin-7 induces the association of phosphatidylinositol 3-kinase with the
      alpha chain of the interleukin-7 receptor.
AB  - The recently characterized receptor for interleukin (IL)-7 (IL-7R) includes a
      unique alpha chain as well as a common gamma chain shared with the receptors for
      IL-2 and IL-4. Engagement of the IL-7R activates the intracellular enzyme
      phosphatidylinositol (PtdIns) 3-kinase but the mechanism of PtdIns 3-kinase
      activation and the molecular basis of its interaction with IL-7R are not known.
      Here we show that IL-7 causes the 85-kDa regulatory subunit of PtdIns 3-kinase
      (p85), and PtdIns 3-kinase activity, to associate with the IL-7R. This
      interaction can be ascribed to ligand-induced phosphorylation of a single Tyr
      residue in the receptor's unique alpha chain. Herbimycin A, a specific protein
      tyrosine kinase inhibitor, suppresses not only tyrosine phosphorylation of the IL
      7R but also its association with p85. A phosphopeptide corresponding to the
      sequence surrounding Tyr449 in the cytoplasmic tail of the IL-7R alpha chain, but
      not its non-phosphorylated analogue or phosphopeptides coincident with the
      sequences surrounding other alpha chain Tyr residues, efficiently competes out
      p85 binding. Replacement of Tyr449 with Phe results in a loss of p85 binding.
      Finally, soluble forms of the src homology 2 domains of p85, which bind directly
      to phosphotyrosyl peptides, specifically inhibit the association of p85 with the
      IL-7R. Thus, PtdIns 3-kinase recruitment occurs through a single, phosphotyrosine
      dependent recognition motif surrounding Tyr449 in the IL-7R alpha chain. This
      motif corresponds to a canonical sequence for p85 binding, Tyr(P)-X-X-Met. Since
      the closely related IL-2R and IL-4R also activate PtdIns 3-kinase but are devoid
      of such canonical motifs, our results suggest that the mechanism by which IL-7R
      recruits and activates PtdIns 3-kinase differs fundamentally from that used by
      the other receptors. PtdIns 3-kinase may, therefore, play a unique and important
      role in the biological response to IL-7.

PMID- 7522166
TI  - Selective inhibition of E-selectin, ICAM-1, and VCAM in endothelial cells.
AB  - Endothelial cells, as they normally exist in the vasculature as quiescent cells,
      perform several functions. In an inflammatory response, endothelial cells are
      activated to up-regulate a number of genes, including E-selectin (ELAM-1), VCAM
      1, ICAM-1, interleukin (IL)-1, IL-8 and plasminogen activator inhibitor-1 (PAI
      1). Very little is known about factors that regulate the activation process. We
      describe here that a heat-stable protein, normally present in the alpha-globulin
      fraction of serum, inhibits induced expression of E-selectin, ICAM-1, and VCAM-1
      in vitro and also impedes the accumulation of mRNA for these molecules.
      Inhibition of E-selectin, the only gene tested in this respect, is at the level
      of transcription. At the same time, the alpha-globulins do not, under the same
      conditions, repress mRNA accumulation for IL-1, IL-8, or PAI-1. The effect of the
      inhibitor does not relate to constraints on function of nuclear-factor kappa B,
      the induced activity of which is not interfered with at the early time points at
      which the suppression of these three genes is seen.

PMID- 7522167
TI  - Exploring myelin basic protein for HLA class I-binding sequences.
AB  - In view of the increasing evidence of the involvement of CD8+ T cells in the
      pathogenesis of multiple sclerosis (MS), we have scanned the sequence of the
      myelin basic protein (MBP), using 162 overlapping nonapeptides, for HLA-class I
      binding sites. Peptide binding was measured using the recently reported HLA class
      I alpha-chain-refolding assay, and the following HLA allelic products were
      analyzed: HLA-A2 (*0201, *0204), B27 (*2705), B35, B51 and B62. A considerable
      number of binding peptides were distinguished for each of the allelic products
      tested. In addition, three interesting points emerged. The first was the
      identification of several binding peptides which did not contain the known anchor
      motifs. The second was the evidence that several peptides showed a promiscuous
      binding profile, being able to bind to different HLA class I molecules that were
      either allelic or non allelic. The third was that in several cases two
      consecutive peptides could bind to the same HLA molecule.

PMID- 7522168
TI  - Response of interleukin-6-deficient mice to tumor necrosis factor-induced
      metabolic changes and lethality.
AB  - Whether interleukin (IL)-6 contributes to tumor necrosis factor (TNF)-induced
      lethal shock or whether, on the contrary, it is part of a protective feedback
      system, remains unresolved. Here, we report experiments with IL-6 gene-disrupted
      mice (IL-6(0/0)). We have tested the susceptibility of these to TNF-induced
      metabolic changes and lethality in different models, and compared the results
      with those obtained with IL-6+/+ wild-type mice. We studied the response to TNF
      in three different models: (i) murine TNF administration; (ii) TNF in
      galactosamine (GalN)-sensitized mice; (iii) TNF in Bacillus Calmette-Guerin
      sensitized mice. We observed no significant difference between the two types of
      mice in any of the three models. Furthermore, IL-6(0/0) mice could be equally
      well desensitized (by IL-1) to TNF/GalN-induced lethality and tolerized to TNF
      induced shock as IL-6+/+ mice. We also observed that, in response to turpentine,
      TNF or IL-1, IL-6(0/0) mice produced significantly less acute phase proteins
      (APP) than IL-6+/+ mice. In IL-6(0/0) mice, less corticosterone was induced by
      TNF than in the control mice, while the response to adrenocorticotropic hormone
      was the same. The results indicate that IL-6 is not contributing in a major way
      to the pathogenesis leading to TNF-induced shock, and that neither IL-6 nor the
      APP studied are essential for a protective feedback system.

PMID- 7522169
TI  - Homotypic aggregation of CD103 (alpha E beta 7)+ lymphocytes by an anti-CD103
      antibody, HML-4.
AB  - One monoclonal antibody, HML-4, directed against the alpha E beta 7 integrin
      (CD103), an integrin preferentially expressed on human intestinal intraepithelial
      lymphocytes (IEL), induced the homotypic aggregation of IEL and of a CD103+
      MOLT16 cell line. Aggregation was an active adhesion event dependent on an intact
      cytoskeleton, on tyrosine phosphorylation but not on activation of protein kinase
      C. It was blocked by four other anti-CD103 antibodies but by none of the
      antibodies blocking known adhesion lymphocyte pathways. It was associated with a
      redistribution of the CD103 integrin in the areas of cell-cell contacts. These
      results indicated that HML-4-induced homotypic adhesion was mediated via CD103
      and resulted from the binding of the integrin to an as yet undefined ligand
      expressed by CD103+ cells. This ligand was distinct from the epithelial ligand of
      CD103: in contrast with homotypic adhesion, heterotypic adhesion of CD103+ MOLT16
      cells on two epithelial intestinal cell lines (DLD1 and HT29) was dependent on
      the presence of divalent cations, was not enhanced by HML-4, was inhibited by HML
      1 but not by the three other antibodies with an inhibitory effect on homotypic
      adhesion. Finally, the study of conjugates between CD103+ and CD103- sublines
      derived from the MOLT16 cell line suggested that HML-4-induced homotypic
      aggregation resulted from homophilic CD103-CD103 interactions.

PMID- 7522170
TI  - Vasoactive intestinal peptide specifically induces human IgA1 and IgA2
      production.
AB  - The effects of vasoactive intestinal peptide (VIP) on human IgA1 and IgA2
      production were studied. In unfractionated small resting B cells stimulated with
      anti-CD40 monoclonal antibody (mAb), VIP induced IgA1 and IgA2 production without
      affecting the production of IgG1, IgG2, IgG3, IgG4, IgM, or IgE. When small B
      cells were separated into sIgA1+, sIgA2+, sIgA1- and sIgA2- B cells, anti-CD40
      mAb plus VIP induced IgA1 and IgA2 production by surface IgA1- (sIgA1-) and sIgA2
      B cells, respectively, while having no effect on sIgA1+ and sIgA2+ B cells. This
      induction by VIP was specific, since anti-CD40 mAb plus other neuropeptides,
      i.e., somatostatin or substance P, had no effect, and moreover, the induction was
      specifically blocked by a VIP antagonist. Further, anti-CD40 mAb plus various
      cytokines, including interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL
      10, transforming growth factor-beta, low molecular weight B cell growth factor,
      and interferon-gamma, did not induce IgA1 and IgA2 production by sIgA1- and sIgA2
      B cells, respectively. These results indicate that in the presence of anti-CD40
      mAb, VIP induces IgA1 and IgA2 production by isotype switching.

PMID- 7522171
TI  - Endothelin-1 induces release of histamine and leukotriene C4 from mouse bone
      marrow-derived mast cells.
AB  - Whether specific binding sites for endothelin-1 and endothelin-3 exist in mouse
      bone marrow-derived mast cells (BMMC) and if these endothelins are capable of
      stimulating chemical mediator release from the cells was investigated. A single
      component of binding sites for endothelin-1 was found in the cells, but no
      binding sites for endothelin-3 were observed. Endothelin-1 at 1-100 nM
      concentration dependently induced release of histamine and immunoreactive
      leukotriene C4 from BMMC, while endothelin-3 at up to 100 nM did not stimulate
      the release of either mediator. Time course experiments revealed that the release
      of histamine and immunoreactive leukotriene C4 induced by endothelin-1 occurred
      rapidly, reaching near maximal levels within 20 s and 2 min, respectively, after
      the stimulation, while histamine release induced by antigen, at the concentration
      which induced an extent of release similar to that induced by 100 nM endothelin
      1, required comparatively prolonged incubation (approximately 10 min for
      submaximal levels). Cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), a selective
      antagonist of endothelin ETA receptors, not only dissociated [125I]endothelin-1
      specifically bound to BMMC but also inhibited the release of both mediators from
      endothelin-1-induced cells. These results suggested strongly that BMMC have
      endothelin ETA receptors on their cell membrane, stimulation of which leads to
      chemical mediator release, probably via a mechanism different from that involved
      in the antigen-induced release.

PMID- 7522172
TI  - Intracisternally injected galanin-(1-15) modulates the cardiovascular responses
      of galanin-(1-29) and the 5-HT1A receptor agonist 8-OH-DPAT.
AB  - In view of the demonstration of specific binding sites for [125I]galanin-(1-15)
      in several brain areas including the nucleus of the solitary tract, possibly
      indicating the existence of multiple galanin receptor subtypes, the effects of
      intracisternal injections of galanin-(1-15) on cardiovascular parameters were
      studied. The effects of co-injections of galanin-(1-15) and galanin-(1-29) and co
      injections of galanin-(1-15) and the 5-HT1A receptor agonist 8-OH-2-(di-n
      propylamino)tetralin (8-OH-DPAT) were also evaluated. Galanin-(1-15) produced a
      significant increase in mean arterial blood pressure (maximum effect 10% at 3
      nmol of galanin-(1-15)) and in heart rate (maximum effect 12% at 1 nmol). When
      threshold doses of galanin-(1-15) (0.1 nmol) and galanin-(1-29) (3 nmol) were
      injected simultaneously they elicited an increase in mean arterial blood
      pressure. The vasodepressor response induced by an ED50 dose of 8-OH-DPAT (6
      nmol) was not modulated by a threshold dose of galanin-(1-15), but the increase
      in heart rate area induced by galanin-(1-15) alone was no longer observed. When
      threshold doses of both galanin-(1-15) and 8-OH-DPAT (0.3 nmol) were co-injected
      a vasodepressor response developed and on heart rate a tachycardic response was
      seen in the peak effects and the overall tachycardic response induced by galanin
      (1-15) was sustained. The results show a different role for galanin-(1-15) as
      compared with galanin-(1-29) in central cardiovascular control.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7522174
TI  - The 5-lipoxygenase inhibitors ZD2138 and ZM230487 are potent and selective
      inhibitors of several antigen-induced guinea-pig pulmonary responses.
AB  - The non-redox 5-lipoxygenase inhibitor Zeneca ZD2138 (6-[(3-fluoro-5-[4-methoxy
      3,4,5,6-tetrahydro-2H-pyran-4-yl])phenoxy- methyl]-1-methyl-2-quinolone) was
      evaluated for its ability to inhibit antigen-induced leukotriene release from
      guinea-pig lung in vitro and antigen-induced increases in pulmonary resistance in
      guinea pigs in vivo. ZD2138 inhibited antigen-induced release of leukotriene D4
      and leukotriene B4 with IC50 values of 0.3 +/- 0.06 microM and 0.4 +/- 0.09
      microM, respectively. At about ten times higher concentrations, ZD2138 had no
      effect on antigen-induced release of thromboxane B2, indicating selectivity for
      inhibition of 5-lipoxygenase vs. phospholipase A2, cyclooxygenase, or thromboxane
      synthetase. Similarly, ZD2138 did not inhibit histamine release, indicating that
      the compound did not have a generalized effect on the mediator release processes.
      Zeneca ZM230487-(6-[(3-fluoro-5-[4-methoxy- 3,4,5,6-tetrahydro-2H-pyran-4
      yl])phenoxymethyl]-1-ethyl-2-quinolone), the N-ethyl analog of ZD2138, was
      approximately equipotent toward inhibition of antigen-induced leukotriene D4
      release, with an IC50 of 0.2 +/- 0.08 microM. The so-called 5-lipoxygenase
      activating protein (FLAP) inhibitor, MK-886 (3-[1-(p-chlorobenzyl)-5-(isopropyl)
      3-tert-butylthioindol-2-yl]-2 ,2- dimethylpropanoic acid), and the iron ligand 5
      lipoxygenase inhibitor zileuton (N-(1-benzo[b]thien-2-ylethyl)-N-hydroxy-urea)
      were also active, but less potent than ZD2138 with IC50 values for inhibition of
      antigen-induced leukotriene release in vitro of 9.3 +/- 3.2 microM and 14.8 +/-
      1.8 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522173
TI  - Evidence that histamine is involved as a mediator of endothelium-dependent
      contraction induced by A23187 in bovine intrapulmonary vein.
AB  - This study was initiated to test the hypothesis that histamine can act as an
      endothelium-derived contracting factor in bovine isolated intrapulmonary vein.
      The effects of calcium ionophore, calcimycin (A23187), on isometric tension were
      compared in unstimulated rings of intrapulmonary vein with and without
      endothelium. A23187 (0.1-10 microM) induced concentration-related contraction
      when endothelium was present. Destruction of endothelium markedly inhibited
      A23187-induced contraction. Methylene blue, hemoglobin or NG-methyl-L-arginine
      significantly enhanced A23187-induced contraction only in venous rings with
      endothelium consistent with attenuation of the contraction by the concomitant
      release of endothelium-derived relaxing factor (nitric oxide) [EDRF(NO)].
      Histamine H1 receptor antagonists inhibited, and iproniazid enhanced, contraction
      elicited by A23187. A23187 induced release of greater amounts of histamine from
      venous rings with than without endothelium. A23187-induced contraction was not
      mimicked by the mast cell activator, compound 48/80, and was not inhibited by
      preexposure to compound 48/80 or in the presence of cromolyn or doxantrazole.
      A23187-induced contraction was not inhibited by pretreatment with indomethacin,
      phentolamine, lipoxygenase inhibitors or superoxide dismutase. The results
      indicate that A23187 induces endothelium-dependent contraction in bovine
      intrapulmonary vein and support histamine as one major mediator involved. The
      association of destruction of endothelium with an inhibition of both A23187
      induced contraction and histamine release is consistent with the endothelium as a
      source for histamine which can exert a local vasoconstrictor effect in bovine
      intrapulmonary vein.

PMID- 7522175
TI  - Septide but not substance P stimulates inhibitory neurons in guinea-pig ileum.
AB  - Recent evidence suggests that [pGlu6,Pro9]substance P-(6-11) (septide) may act on
      unusual tachykinin receptors. Here, we investigated the mechanisms of action of
      septide and other agonists acting on tachykinin NK1 receptors, in the guinea-pig
      ileum. Responses to septide but not to substance P or [Sar9,Met(O2)11]substance P
      were significantly (P < 0.01) potentiated by 1 microM tetrodotoxin. The data
      suggest that septide not only acts directly on smooth muscle tachykinin receptors
      to produce contraction, but also stimulates another receptor subtype on myenteric
      neurons to release inhibitory substance(s).

PMID- 7522177
TI  - Staurosporine inhibits the anaphylactic reaction of the isolated guinea-pig
      heart.
AB  - Isolated hearts from ovalbumin sensitized guinea-pigs were perfused according to
      Langendorff. Ovalbumin injection decreased coronary flow. Left ventricular
      pressure amplitude and heart rate increased initially and decreased thereafter.
      Concomitantly, the liberation of histamine, prostaglandin F2 alpha, as well as
      the sum of leukotrienes C4/D4/E4/F4, measured in the perfusate by
      radioimmunoassay, was augmented. Staurosporine (1 microM), an inhibitor of
      protein kinases, did not influence the liberation of mediators in response to
      antigen challenge, but inhibited all mechanical responses. Infusion of phorbol
      myristate acetate, an activator of protein kinase C, into non-sensitized hearts
      decreased coronary flow and left ventricular pressure amplitude, but did not
      liberate mediators. Staurosporine (1 microM) abolished these mechanical
      responses. The results indicate that staurosporine suppresses cardiac anaphylaxis
      by blockage of mediator effects rather than by inhibition of liberation or
      formation of mediators.

PMID- 7522176
TI  - Inhibition of human platelets and polymorphonuclear neutrophils by the potent and
      metabolically stable prostaglandin D2 analog ZK 118.182.
AB  - The actions of the novel metabolically stable and selective prostaglandin D2
      receptor agonist ZK 118.182 ((5Z,13E)-(9R,11R,15S)-9-chloro-15-cyclohexyl-15-
      hydroxy-16,17,18,19,20-pentanor-3-oxa-5,13-prostadienoic acid) were studied in
      human platelets and polymorphonuclear neutrophils in vitro and compared to the
      naturally occurring agonist prostaglandin D2. ZK 118.182 inhibited collagen and
      ADP induced platelet aggregation more potently than prostaglandin D2 (IC50: 15 nM
      versus 60 nM) but was less effective than the stable prostacyclin mimetic
      iloprost (IC50: 3 nM). The same rank order of potencies was observed for the
      inhibition of collagen-induced platelet ATP secretion. A dose-dependent
      activation of adenylate cyclase could be demonstrated by ZK 118.182 which was
      comparable to that of prostaglandin D2 with respect to the concentration needed
      for half maximal stimulation (ED50) maximal cAMP level achievable. ZK 118.182
      also dose dependently reduced the formyl-methionyl-leucyl-phenylalanine (FMLP) or
      platelet-activating factor (PAF) induced activation of polymorphonuclear
      neutrophils. Both, the oxygen burst resulting in the generation of superoxide
      anions and the degranulation of polymorphonuclear neutrophils accompanied by
      release of the lysosomal enzyme beta-glucuronidase, were significantly and dose
      dependently inhibited. ZK 118.182 was more potent than prostaglandin D2 in
      inhibiting polymorphonuclear neutrophil activation in all tests performed. In
      summary, ZK 118.182 is a prostaglandin D2 mimetic exerting potent inhibitory
      effects on human platelets and polymorphonuclear neutrophils.

PMID- 7522179
TI  - Highly potent substance P antagonists substituted with beta-phenyl- or beta
      benzyl-proline at position 10.
AB  - In the guinea-pig ileum tissue, [Pro9]substance P, a tachykinin NK1 receptor
      selective agonist and septide, [pGlu6,Pro9]-substance P-(6-11), do not interact
      with the same receptor as shown by the different inhibitory profiles of GR 72251
      and [D-Pro9,Pro10,Trp11]substance P. Substitution at position 10 of the D-Pro9
      Pro10 moiety with bulky N-methylated amino acids increased the antagonist potency
      for the tachykinin NK1 receptor without affecting that for the 'septide-sensitive
      receptor'. The incorporation of a trans-beta-L-substituted proline in position
      10, for example a benzyl group (beta-benzyl-L-proline), afforded a potent
      antagonist active in the nanomolar range. For GR 82334, this increase in potency
      was obtained at the expense of selectivity for tachykinin NK1 and 'septide
      sensitive' receptors.

PMID- 7522178
TI  - Effects of L-glutamate on the responses to nerve stimulation in rat isolated
      atria.
AB  - In rat atria isolated with their sympathetic fibres the chronotropic responses to
      nerve stimulation with pulses of 2 ms duration were reduced in a concentration
      dependent manner by 10 microM to 1 mM L-glutamate (Glu) and by 0.01 to 1.00
      microM (R,S)-3-hydroxy-5-methoxyloxasole-4-propionic acid (AMPA), whereas they
      were unaffected by other agonists of Glu receptors such as 1 microM to 1 mM N
      methyl-D-aspartic acid (NMDA), 10 microM to 1 mM kainate and 1 to 100 microM (+/
      )-2-amino-4-phosphonobutyric acid (AP4). The reductions in the atrial responses
      to nerve stimulation caused by Glu were not accompanied by alterations in either
      the basal efflux of [3H]noradrenaline or its overflow in response to the
      stimulation. The sensitivity of the atria to exogenous noradrenaline was not
      modified by either Glu or AMPA. The decreases in the chronotropic responses
      caused by Glu and by AMPA were prevented by both the non-selective Glu receptor
      antagonist, 100 microM kynurenic acid, and the selective AMPA receptor
      antagonist, 10 to 50 microM 6,7-dinitroquinoxaline-2,3-dione (DNQX). In addition,
      the adenosine receptor antagonist, 8-phenyltheophylline (10 microM), as well as
      the muscarinic acetylcholine receptor antagonist, atropine (3 microM), prevented
      the inhibitory effects of both Glu and AMPA on the chronotropic responses of rat
      isolated atria. Since both adenosine and acetylcholine are known to exert
      negative inotropic and chronotropic effects in cardiac tissues, it is proposed
      that Glu could contribute, through the interaction with receptors of the AMPA
      type, to facilitate the release of adenosine and acetylcholine from the
      atria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522180
TI  - Metalloporphyrins inhibit nitric oxide-dependent cGMP formation in vivo.
AB  - Sodium nitroprusside produced a dose-dependent increase in extracellular levels
      of cGMP in the cerebellar cortex in vivo. This was independent of nitric oxide
      synthase activity. The metalloporphyrins zinc-protoporphyrin-IX, tin
      protoporphyrin-IX and zinc-deuteroporphyrin-IX,2,4-bis glycol prevented the
      increase in cGMP in the cerebellar cortex produced by sodium nitroprusside. At
      high doses, tin-protoporphyrin-IX also decreased the basal extracellular levels
      of cGMP. These drugs had no effect on nitric oxide synthase activity. We conclude
      that the neuropharmacological effects of metalloporphyrins may result from their
      direct inhibition of soluble guanylyl cyclase, rather than from an effect on
      carbon monoxide synthesis.

PMID- 7522181
TI  - Sensitive detection and enumeration of CD34+ cells in peripheral and cord blood
      by flow cytometry.
AB  - Peripheral blood stem cell autografts are increasingly used to reconstitute
      hematopoiesis after intensive, potentially marrow-ablative therapy. Assessment of
      autograft adequacy by enumeration of hematopoietic progenitors in colony-forming
      assays is handicapped by lack of reproducibility and prolonged assay time.
      Alternative approaches of graft assessment by flow-cytometric enumeration of
      stem/progenitor cells bearing the CD34 antigen can be hampered by low specificity
      and sensitivity. Here, we report a rapid and reliable multiparameter flow
      cytometric approach to accurately enumerate CD34+ cells in peripheral blood (PB)
      mononuclear cells (MNCs). Total nucleated white blood cells (WBCs) are quantified
      by staining with fluorescein isothiocyanate (FITC)-conjugated CD45 antibody.
      Simultaneous staining by phycoerythrin (PE)-conjugated CD34 antibody defines an
      approximate number for the CD34+ progenitor/stem cell subfraction. When starting
      CD34+ cell numbers are low (0.01-0.5%), other nonspecifically stained leukocytes
      make accurate enumeration impossible. However, when the CD34+ fraction is
      analyzed for CD45 expression vs. side scatter (granularity), true CD34+ blast
      cells form a discrete cluster exhibiting low-density CD45 expression and low side
      scatter characteristics. Cells within this "blast region" can be readily
      distinguished from lymphocytes, monocytes, granulocytes, and other events that
      can contaminate the CD34+ population. Here, we used this sensitive procedure to
      enumerate CD34+ cells in steady-state PB samples (0.03-0.09%), normal bone marrow
      (BM) aspirates, and umbilical cord blood collections (0.33-1.98%). This approach
      thus provides a means to analyze CD34+ cells in specimens from patients who have
      been extensively treated with chemotherapy and those undergoing PB stem cell
      mobilization with cytokines. Additionally, it is useful for assessment of CD34+
      cells in a variety of clinical samples exhibiting perturbations of the
      hematopoietic progenitor/stem cell compartments.

PMID- 7522183
TI  - The ex vivo function and expression of function-associated antigens of peripheral
      blood neutrophils and monocytes.
AB  - The availability of recombinant human granulocyte and granulocyte-macrophage
      colony-stimulating factors (rhG-CSF and rhGM-CSF) has prompted many studies of
      the analysis of antigen expression and function of monocytes and neutrophils from
      patients receiving these factors as therapeutic agents. Preparatory procedures
      for leukocytes are known to alter antigen expression and so function. We
      therefore investigated the use of a novel procedure in which live leukocytes are
      analyzed by flow cytometry without isolation from blood. The expression levels of
      CD11b, CD13, CD14, CD16, and CD18 antigens and L-selectin (TQ1 and Leu-8
      epitopes) on neutrophils and monocytes from 15 normal individuals were determined
      and compared with a previously used method in which the leukocytes were fixed and
      the erythrocytes lysed before analysis. Significant differences for the apparent
      expression of CD11b, CD18, and L-selectin were observed between the two methods.
      The reasons for this were investigated. Since the new method allowed analysis of
      live cells, we also investigated whether modulation of antigen expression could
      be determined following receptor agonist interaction. This was found to be easily
      achievable, and we advocate using the new procedure where possible for the ex
      vivo analysis of function and function-associated antigens on monocytes and
      neutrophils.

PMID- 7522182
TI  - The c-kit proto-oncogene receptor is expressed on a subset of human CD3-CD4-CD8-
      (triple-negative) thymocytes.
AB  - The c-kit receptor is a tyrosine-kinase transmembrane receptor first identified
      as an oncogene in the HZ4-feline leukemia virus and later found to be important
      in hematopoiesis in mice. The ligand for this receptor (Steel factor) can
      stimulate hematopoiesis both in vitro and in vivo. To study the pattern of c-kit
      receptor expression in normal human hematopoietic progenitor cells, we prepared a
      monoclonal antibody (9B9) against human c-kit receptor by using a synthetic
      peptide (amino acids 476-501) from the extracellular domain of c-kit receptor to
      immunize Balb/c mice. Monoclonal antibody 9B9 bound to recombinant c-kit protein,
      the erythroleukemic line HEL, the megakaryocytic line MEG-01, and the murine mast
      cell line P815. Monoclonal antibody 9B9 also bound to the surface of the CD7+CD3
      CD4-CD8- T cell lymphoid cell lines DU.528 and HSB2T, and also to 1 to 4% of
      normal bone-marrow cells. The majority (67 +/- 6%) of CD34+ bone-marrow
      progenitor cells coexpressed c-kit receptor. Flow-cytometry analysis of immature
      CD3-CD4-CD8- (triple-negative) thymocytes indicated 30 +/- 9.5% expressed the c
      kit receptor, and thymidine incorporation assay revealed that the receptor is
      functional. Indirect fluorescent microscopy of human thymic tissue, using a
      monoclonal antibody against Steel factor, revealed its presence on scattered
      mononuclear cells within the intralobular septae and the subcapsular cortex,
      which are regions where the triple-negative thymocytes are also localized. These
      data provide evidence that the c-kit receptor is present on human hematopoietic
      bone marrow and intrathymic T cell progenitor cells, and that it likely plays a
      role in early T cell lymphopoiesis.

PMID- 7522184
TI  - A time course study for optimal harvest of peripheral blood progenitor cells by
      granulocyte colony-stimulating factor in healthy volunteers.
AB  - In a search for the optimal method to harvest peripheral blood progenitor cells
      (PBPC) without myeloablative chemotherapy, we administered recombinant human
      granulocyte colony-stimulating factor (G-CSF) to adult, healthy volunteers and
      investigated the mobilization rate of the PBPC. The consecutive subcutaneous
      administration of G-CSF in a dose of 2 micrograms/kg/d for 5 days significantly
      increased colony-forming units-granulocyte/macrophage (CFU-GM) up to 2340 +/- 980
      per mL whole blood with a 30 +/- 21-fold mobilization of PBPC, range 11- to 76
      fold. Burst-forming units-erythroid (BFU-E) and mixed erythroid progenitors (CFU
      Mix) were also increased, and the mobilization rate was 8.4 +/- 4.5-fold and 7.6
      +/- 4.7-fold, respectively. A time course study of PBPC after final G-CSF
      injection was done for 0 to 30 hours on days 1, 3, and 5. After a single
      administration of G-CSF (day 1), there was no increment of PBPC during the
      subsequent 30 hours, but the white blood cell count (WBC) markedly increased.
      Three days after the injection of G-CSF, no increase of CFU-GM was seen during
      the first 2 hours, then a significant, time-dependent increase occurred for up to
      30 hours. Five days after the injection of G-CSF, there was no increase of CFU-GM
      during the first 2 hours, and the significant increase at 24 hours was maintained
      for up to 30 hours. BFU-E and CFU-Mix showed the same pattern of expansion as
      seen with CFU-GM. Thus, subcutaneous administration of 2 micrograms/kg/d G-CSF
      for 5 days will lead to a successful PBPC harvest for transplantation, and the
      most suitable period for this is 24 to 30 hours after the final G-CSF
      administration.

PMID- 7522185
TI  - Involvement of the c-kit receptor in the adhesion of hematopoietic stem cells to
      stromal cells.
AB  - The proto-oncogene c-kit, encoding a receptor-type tyrosine kinase, is allelic
      with the W locus of the mouse. The stromal cell line OP9, capable of supporting
      long-term hematopoiesis, was newly established from a newborn B6C3F1-op/op mouse
      calvaria. When bone marrow cells of WBB6F1-W/Wv mice were cocultured with the OP9
      cells in liquid medium, hematopoiesis declined to a level one-thousandth of that
      in the cocultures of bone marrow cells of WBB6F1-+/+ mice and stromal cells by
      day 21. In contrast, when bone marrow cells of W/Wv mice were cocultured with OP9
      cells in semisolid medium, at least 61% of the number of colonies were detected
      until the end of our observation period of 42 days when compared with that in
      control cocultures, although colonies formed by hematopoietic stem cells of W/Wv
      mice were significantly smaller than those of normal stem cells. After a 24-hour
      incubation with OP9 cells, fewer stem cells of W/Wv mice than normal ones adhered
      to the stromal cells. Adhesion of normal stem cells to stromal cells was
      inhibited by the addition of an antagonists anti-c-kit monoclonal antibody, ACK2.
      These results demonstrate that the c-kit receptor plays an important role not
      only in the proliferative response of hematopoietic stem cells but also in their
      adhesion to stromal cells.

PMID- 7522187
TI  - Characterization of peripheral blood CD34+ progenitor cells mobilized with
      chemotherapy and granulocyte colony-stimulating factor.
AB  - Peripheral blood (PB) mononuclear cells mobilized with chemotherapy and
      granulocyte colony-stimulating factor (G-CSF) were enriched in CD34+ cells;
      aliquots were seeded in long-term cultures (LTC) on bone marrow (BM)-derived
      stromal layers and in liquid cultures containing various growth factors. The
      final recovery of PB CD34+ cells was similar to normal BM controls, and no
      difference was found in the expression of CD33 and CD13 antigens; a lower number
      of CD34+/HLA-DR- cells was found in PB with respect to BM samples (p < 0.001). PB
      cells sustained hematopoiesis in LTC at least as long as BM cells. At week 3 and
      4, PB total mononuclear cell (MC) and CD34(+)-selected cell cultures showed a
      higher nonadherent cell recovery compared to the respective BM controls (p = 0.05
      and p < 0.01). The liquid culture of PB CD34+ cells in the presence of
      granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3),
      and stem cell factor (SCF) resulted in a marked and long-lasting increase of
      colony-forming units-granulocyte/macrophage (CFU-GM). Taken together, our data
      suggest that chemotherapy and G-CSF-primed cells contain a considerable number of
      both committed and early precursors, accounting for the rapid hematopoietic
      recovery observed after their reinfusion following myeloablative chemotherapy.

PMID- 7522188
TI  - Vascular cell adhesion molecule-1 expressed by peritoneal mesothelium partly
      mediates the binding of activated human T lymphocytes.
AB  - Adhesion molecules such as selectins and integrins are known to mediate leukocyte
      attachment and transmigration through activated vascular endothelium. However,
      the molecules that mediate subsequent leukocyte entry into nonvascular spaces
      such as the abdominal cavity during states of peritoneal inflammation have not
      been identified. Because the peritoneal mesothelial lining represents the final
      barrier to leukocyte migration into the abdomen, it is likely that adhesion
      molecules expressed by mesothelial cells are involved in this process. We have
      developed an in vitro binding assay using confluent layers of normal human
      mesothelial cells to determine which adhesion molecules might be involved in T
      lymphocyte-mesothelial recognition. Normal peripheral blood T lymphocytes exhibit
      low-level specific binding to mesothelium (mean 13% specific binding, n = 4),
      which is enhanced by phorbol myristate acetate (PMA) treatment (mean 38% specific
      binding, n = 4). This binding is significantly inhibited in the combined presence
      of antibodies reactive with CD29 and CD18, suggesting a role for beta 1 and beta
      2 integrins, respectively, in this interaction. Interestingly, cultured human
      mesothelial cells were shown to express vascular cell adhesion molecule-1 (VCAM
      1), suggesting that this molecule might function as a counter-receptor for alpha
      4 beta 1 expressed by T lymphocytes. Mesothelial cells were also noted to express
      ICAM-1, CD29, and CD44, but not CD18 or selectins. VCAM-1 expression was not a
      constitutive property of freshly obtained mesothelial cells but was inducible
      upon culture in the presence of either interleukin-1 (IL-1), tumor necrosis
      factor (TNF), or PMA. Neutralizing antibodies reactive with either alpha 4, VCAM
      1, or CD29 were all equally capable of inhibiting the binding of activated
      leukocytes to mesothelial cells (in the presence of anti-CD18 antibody).
      Mesothelial VCAM-1 was found to have a molecular mass of 110 kD and an mRNA
      transcript of approximately 3.2 kb, consistent with the predominant VCAM-1
      species found in activated endothelium. These data suggest that functional VCAM-1
      is expressed on activated mesothelial cells and may play a role in the distal arm
      of leukocyte trafficking to the abdominal cavity.

PMID- 7522186
TI  - The growth response of Lin-Thy-1+ hematopoietic progenitors to cytokines is
      determined by the balance between synergy of multiple stimulators and negative
      cooperation of multiple inhibitors.
AB  - The present studies investigated the balance of positive and negative growth
      signals in direct regulation of hematopoiesis. Interleukin-3 (IL-3) combined with
      Steel factor (SLF) optimally stimulated proliferation of Lin-Thy-1+ murine bone
      marrow progenitors in single-cell assays, and that proliferation was inhibited
      more than 90% by transforming growth factor-beta 1 (TGF-beta 1). Colony
      stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor
      (GM-CSF), IL-1, or IL-6 as a third stimulatory growth factor was incapable of
      counteracting the TGF-beta 1-mediated inhibition of IL-3-plus-SLF-stimulated
      growth, while G-CSF slightly enhanced the number of TGF-beta 1-resistant clones.
      As a fourth factor, only IL-1 could partially overcome the TGF-beta 1-induced
      growth inhibition. While the presence of a cocktail of five additional
      stimulatory growth factors did not enhanced the frequency of single Lin-Thy-1+
      progenitors proliferating in response to IL-3 plus SLF, the number of responding
      progenitors in the presence of TGF-beta 1 was enhanced nine-fold. Furthermore,
      tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), but not
      macrophage inflammatory protein-1 alpha (MIP-1 alpha), cooperated with TGF-beta 1
      to reverse the proliferative effects of multiple stimulatory cytokines, resulting
      in 76% inhibition. Thus, the direct effects of single inhibitory factors on
      hematopoietic progenitor cell growth can be reversed by multiple stimulatory
      growth factors, and negative growth factors can directly cooperate to suppress
      progenitor cell growth stimulated by multiple positive-acting factors.

PMID- 7522190
TI  - Immunocytochemical detection of bone marrow-invasive neuroblastoma cells.
AB  - We evaluated the utility of an immunocytochemical technique employing the
      commercially available anti-CD56 monoclonal antibody, NKH 1. The utility and
      sensitivity of this technique in the detection of invasive neuroblastoma (NB)
      cells in the bone marrow were compared with those of Wright-Giemsa staining. The
      correlation coefficient for the percent NB cells detected using Wright-Giemsa
      staining with the percent NKH 1 immunoreactive cells was 0.78. In the analysis of
      specificity, this monoclonal antibody showed slight cross-reactivity with normal
      bone marrow cells, including macrophages, lymphocytes and osteoblasts. In the
      evaluation of the sensitivity of the NKH 1 immunocytochemical technique, SK-N-DZ
      and SK-N-SH NB cell lines were added to morphologically normal bone marrow
      mononuclear cells from patients without NB to the final NB cell line at
      concentrations of 2%, 1% and 0.1%. NB cells at the final concentration of 0.1%
      could be detected by the immunocytochemical technique. We conclude that the NKH 1
      immunocytochemical staining technique is useful in the detection of metastatic NB
      cells in bone marrow.

PMID- 7522191
TI  - Unassembled (soluble) vimentin in human myeloid leukemia cell line HL60.
AB  - The intermediate filament proteins which include vimentin, desmin, and the
      keratins are one of three major classes of cytoskeletal proteins in eukaryotic
      cells. In this study we found that most of the vimentin of undifferentiated HL60
      and cells induced to differentiate either along the monocytoid pathway by 12-O
      tetradecanoylphorbol-13-acetate (TPA) or along the granulocytic pathway by
      retinoic acid was soluble in a buffer containing 1% Triton X-100/0.6 mol/l KCl in
      which the intermediate filament proteins usually are not soluble. HL60 vimentin
      separated on polyacrylamide gel electrophoresis into two proteins of Mr 55,000
      and 54,000 that we detected by immunoblotting. The Mr 55,000 species was the
      major form in undifferentiated HL60 cells and cells induced by retinoic acid. The
      distribution of both forms of vimentin changed during induction of
      differentiation by TPA and after 24 h the Mr 54,000 species was predominant.
      After an additional 24 h exposure to TPA the relative levels of the two forms of
      vimentin approached equivalence and a high level of vimentin degradation products
      was seen. These results suggest that TPA may increase vimentin degradation along
      a pathway that has a Mr 54,000 intermediate. In addition, the high levels of
      soluble vimentin in HL60 cells suggests that these cells may be a good model for
      studying components involved in vimentin assembly.

PMID- 7522189
TI  - Administration of three cytokines instead of bone marrow transplantation in an
      HIV+ patient with high-grade lymphoma.

PMID- 7522192
TI  - Differential expression of two ICAM-1 epitopes and LFA-1 chains in B-cell non
      Hodgkin's lymphomas.
AB  - B-cell non-Hodgkin's lymphomas (B-NHL) and B-cell areas of reactive
      lymphadenopathies were investigated immunohistochemically for expression of two
      distinct ICAM-1 epitopes, Me14/D12 and P3-58, and the LFA-1 alpha and beta
      chains. Partial or total loss of expression of one or both epitope(s) and/or
      chain(s) was evident in all B-NHL in function of increasing Working Formulation
      (WF) malignancy grade, with most defects in the high-grade tumors, namely the
      lowest detectability of the ICAM-1 Me14/D12 and LFA-1 alpha chain, the lowest co
      expression of ICAM-1 epitopes and LFA-1 chains, and the most frequent
      simultaneous loss. The ICAM-1 and LFA-1 profiles overlapped within the low- and
      intermediate-grades, whereas striking differences between the high-grade subtypes
      were detected. Specifically, Burkitt's and lymphoblastic tumors always lost both
      epitopes and both chains. Large cell, immunoblastic tumors occasionally did so,
      and also showed either uncoordinated expression or co-expression of these
      constituents. It is suggested that expression defects of this type may help
      differentiate malignant from benign lymphoproliferations, and also be involved in
      the progression of B-NHL, since most are observed in high-grade tumors, whose
      ICAM-1 and LFA-1 profiles indicate that their subtypes are the expression of
      distinct normal B-cell differentiation stages.

PMID- 7522196
TI  - Biosynthesis of butirosin in Bacillus circulans NRRL B3312: identification by
      sequence analysis and insertional mutagenesis of the butB gene involved in
      antibiotic production.
AB  - As an approach to an analysis of the biosynthesis of the aminoglycoside
      antibiotic butirosin (But), we investigated the chromosomal regions flanking the
      ButR gene (aphA4/butA) of Bacillus circulans NRRL-B3312, and have identified, by
      nucleotide sequence analysis, a large open reading frame (ORF; ButB) upstream
      from the ButR gene. Hybridization was detected between butB and chromosomal DNA
      from other Bacillaceae that produce But-like compounds (but not from non
      producers). Interruption of this sequence by insertion of an erythromycin
      resistance-encoding gene (erm) at either of two distinct sites eliminated the
      production (biosynthesis or export) of But, thus indicating a role for butB in
      antibiotic production. Gene butB is transcribed in the same direction as butA and
      encodes a protein of 1616 amino acid (aa) residues with a 30-aa N-terminal signal
      peptide. Comparison of the sequence for the translation product (ButB) with the
      aa compositions and sequences of known bacterial surface proteins, such as S
      layer proteins, suggests that this protein is cell-wall associated. It is
      proposed that ButB plays a role in the export of But from the producing organism.

PMID- 7522194
TI  - Integrins as dynamic regulators of vascular function.
AB  - The vascular endothelium lines the entire cardiovascular system and serves as a
      nonthrombogenic and selectively permeable boundary between the blood-stream and
      extravascular space. Endothelial cells are polar cells that are continuously
      subjected to fluid-generated forces on their luminal surface whereas their
      abluminal surface resides on basement membranes/extracellular matrix. The
      integrin family of cell-surface heterodimeric glycoproteins is located along both
      of these surfaces and participates in maintaining the normal endothelium and in
      the dynamic changes associated with the pathophysiology of the endothelium.
      Endothelial cell beta 1 and beta 3 integrins function together with other
      families of adhesion molecules during vasculogenesis, angiogenesis, inflammation,
      and wound healing. Leukocyte beta 1 and beta 2 integrins, in conjunction with
      members of the Ig and selectin gene families expressed on endothelium, mediate
      leukocyte recruitment to sites of inflammation. The structural and functional
      properties of integrins make them uniquely suited to mediate these essential and
      complex processes in the vasculature.

PMID- 7522195
TI  - [Noninvasive serum test for prenatal detection of Down syndrome, other chromosome
      abnormalities and open neural tube defects--a prospective study].
AB  - Between September 1st 1990 and Juli 31st 1993, 5071 pregnant women were screened
      prospectively by the "triple-test", including maternal serum alpha-fetoprotein,
      human chorionic gonadotropin and unconjugated oestriol in order to detect
      chromosomal anomalies and open neural tube defects. The serum samples were
      collected in collaboration with the obstetricians of the region of West
      Mecklenburg and North-West-Brandenburg. Laboratory testing using
      radioimmunoassays was performed between weeks 15 and 20 of gestation, all serum
      specimens being investigated in only one institution. The original alpha-software
      from Wald et al. was the basis for calculating the statistical risk for Down's
      syndrome. Pregnant women with a high risk for Down's syndrome (cutoff > or =
      1:250) were taken care of in a special outpatient clinic including procedures
      like amniocentesis and fetal blood sampling. Amongst 5071 pregnant women, 21
      fetal anomalies were seen. Five cases of Down's syndrome, three of trisomy 18,
      one trisomy 13, two cases of triploidy and four cases of open neural tube
      defects, one 46 xy/45 x mosaic karyotype and one case of gastroschisis could be
      diagnosed correctly. One case of trisomy 21, one case of trisomy 18 and two open
      neural tube defects showed false negative results. Using the cutoff of 1:250 for
      prenatal detection of Down's syndrome and performing ultrasound routinely to
      determine gestational age, the sensitivity of the "triple-test" was 83.33% having
      a specificity of 92.68%. The predictive value of a positive test for prenatal
      diagnosis of Down's syndrome was 1.33%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522193
TI  - Spinal cord stimulation for unreconstructible chronic limb ischaemia.
AB  - There is still a lack of prospective randomised studies; at the present we know
      of only one by Jivegard et al. on a relatively small number of 51 patients. Their
      results are encouraging, tissue loss being reduced significantly and a trend
      towards increased limb salvage. The results of ongoing Dutch and American studies
      are awaited. It has however been shown in convincing microcirculatory studies by
      Jacobs et al. and others that SCS has a positive effect. Wide clinical experience
      has also substantiated this; were this not the case it would be hard to
      understand why elaborate studies by Augustinsson, Meyerson and the prolific work
      of Linderoth should ever have been designed. Recent communications by Lo Gerfo
      and others have shown that it is important to visualise the arterial tree all the
      way down to the foot by selective angiography before pronouncing a leg as non
      reconstructible. The 3- and 5-year patency results of femoro- and popliteo-pedal
      bypass surgery presented by Lo Gerfo are so extraordinary--albeit probably
      unreproducible by all vascular surgeons--that SCS must be restricted to the truly
      unoperable or unreconstructable cases of CLI. SCS therefore is definitely not
      meant to be an alternative to reconstructive techniques!(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7522197
TI  - [Physiological and biogeochemical effect of mineral fertilizers on the human
      body].

PMID- 7522199
TI  - Serum progesterone monitoring in post-molar surveillance.
AB  - Serial serum progesterone and beta human chorionic gonadotropin (beta hCG) levels
      were measured during surveillance of 24 women at risk for development of
      gestational trophoblastic neoplasia (GTN) following evacuation of complete molar
      gestations. Six of the 24 patients developed post-molar GTN. The initial median
      progesterone level of 76 ng/ml in these six patients drawn at evacuation was
      significantly higher than the median of 18 ng/ml in those not developing GTN (P =
      0.026). Additionally, the serum progesterone decreased to < 5 ng/ml within a week
      of evacuation in 16/18 patients without GTN. In 5/6 GTN cases, levels of
      progesterone remained > 5 ng/ml for > or = 3 weeks of the surveillance period (P
      < 0.05). Serum beta hCG levels required 4-11 weeks of surveillance to distinguish
      between non-persistent cases and GTN. We conclude that serial serum progesterone
      levels measured during post-molar surveillance parallel beta hCG regression.

PMID- 7522198
TI  - High-dose methotrexate for gestational trophoblastic disease.
AB  - Eighty patients with low-risk and 5 patients with intermediate-risk gestational
      trophoblastic neoplasia (GTN) (WHO classification) were treated with single-agent
      high-dose methotrexate with folinic acid rescue (MTX/FAR). By the NCI
      classification, 65 patients had nonmetastatic GTN, 13 patients had low-risk
      metastatic GTN, and 7 patients had high-risk metastatic GTN. Seventy-one (84%)
      patients achieved remission (beta HCG < or = 5 IU/liter) with MTX/FAR, whereas 14
      (16%) failed to achieve remission with MTX/FAR alone. All failures were salvaged
      with second-line therapies. Patients successfully treated with MTX/FAR required a
      median of 4 courses to achieve remission, and a median of 2 consolidative
      courses. Factors found predictive of failure with MTX/FAR were pretreatment beta
      HCG (P = 0.003), prior history of GTN (P < 0.04), and time from termination of
      antecedent pregnancy to initiation of treatment (P < 0.05). No significant
      difference was noted between the "success" and "failure" groups with respect to
      MTX dose or infusion time, the timing and dosage of folinic acid rescue, the
      number of courses of MTX, or the mean interval between courses. Multivariate
      analysis revealed that the pretreatment beta HCG (P < 0.01) and short time from
      termination of antecedent pregnancy to initiation of treatment (P < 0.03) were
      independently significant for failure. No significant (grade 3/4) hematologic or
      gastrointestinal toxicity occurred, and no treatment delays or dose reductions
      were required. This regimen is both effective and well tolerated; however, the
      theoretical advantages of high-dose methotrexate do not appear to offer any
      clinical advantage over conventional dose MTX in low- and intermediate-risk GTN.

PMID- 7522201
TI  - Menstrual and hormone patterns in women treated with high-dose cisplatin and
      bleomycin.
AB  - Menstrual and hormone patterns were investigated in 10 fertile women (median age
      37, range 25-43 years) with locally advanced cervical cancer treated with
      neoadjuvant chemotherapy (CT). CT consisted of two cycles of high-dose cisplatin
      (CDDP, 40 mg/m2, Days 1 to 4) and bleomycin (B, 15 mg/m2, Days 1 and 8) separated
      by an interval of 21 days. Menstrual patterns before and during CT were recorded.
      FSH, LH, estradiol, and progesterone were assayed on the day that treatment was
      begun, after 2 and 4 days of CDDP administration, and weekly between and after
      the two cycles. Hormone assays during the first week of CT showed no significant
      change in hormone levels. After the first course of CT, five patients showed
      hypergonadotrophic amenorrhea and five patients maintained menses, two showing
      ovulatory and three showing follicular phase hormone patterns. After the second
      course of CT, one more patient become amenorrheic, and endocrine follow-up showed
      that two patients maintained hypergonadotrophic amenorrhea, four with
      hypergonadotrophic amenorrhea had a return of hormone levels to the follicular
      range of 7-9 weeks after, three maintained follicular phase hormone patterns
      until operation, and one ovulated. Gonadal dysfunction should be included among
      the side effects of high-dose CDDP and B regimens.

PMID- 7522203
TI  - Regulation and physiological role of insulin-like-growth-factor-binding protein-1
      in human granulosa cells.
AB  - The present study was undertaken to elucidate the physiological role and the
      regulation of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) in
      human luteinizing granulosa cells. IGFBP-1 abolished IGF-I-stimulated estradiol
      production by luteinizing granulosa cells in a dose-dependent manner with a 50%
      inhibitory concentration (IC50) of 0.27 nM. Similarly, IGFBP-1 inhibited 125I-IGF
      I binding to granulosa cells. IGFBP-1 was identified by Western immunoblot and
      specific enzyme immunoassay in the granulosa-cell-conditioned medium after 24 h
      culture. Immunoreactive IGFBP-1 released into the medium was inhibited by both
      IGF-I and follicle-stimulating hormone dose-dependently with an IC50 of 0.14 and
      0.13 nM, respectively, while human chorionic gonadotropin-stimulated IGFBP-1
      release with a 50% effective dose (ED50) of 0.6 nM. These results suggest that
      IGFBP-1 is involved in follicular development and granulosa cell differentiation
      in the human ovary and that gonadotropins may influence IGF-I action by modifying
      IGFBP-1 levels within the ovary.

PMID- 7522200
TI  - Chemotherapy followed by radiotherapy versus radiotherapy alone in locally
      advanced cervical cancer: a randomized study.
AB  - Between August 1990 and January 1992, 184 patients with squamous cell carcinoma
      of the cervix, FIGO stage IIB-IVA, were randomized to receive either two cycles
      of bleomycin, ifosfamide-mesna, and cis-platinum (BIP) chemotherapy (CT) followed
      by radiotherapy (RT) ("CT-RT group," n = 94) or RT alone (RT group, n = 90). In
      the CT-RT group, of 89 evaluable patients, 64 responded: complete response (CR) 4
      (4.5%) and partial response 60 (67.5%). Of the remaining 25 patients, 23 had
      stable disease and 2 progressed. Eighty of 89 patients completed RT as planned.
      Following RT 56 (70%) achieved CR, 19 (23.7%) had residual disease, and 5 (6.3%)
      had progressed. CT responders had a better response to RT: 83% (49/59) vs 33.3%
      (7/21), P < 0.01). The stage of disease, histologic grade, duration of symptoms,
      and history of smoking had no influence on the response to CT. Patients aged > 45
      years and those with Hb > 10 g/dl had significantly better response.
      Nausea/vomiting, alopecia, grade I-II myelosuppression, diarrhea, and mucositis
      were the major side effects of CT. Two patients died of CT toxicity. In the RT
      group, 88 patients were evaluable: 61 (69.3%) patients achieved CR, 25 had
      residual disease, and 2 progressed. The side effects of RT were cystitis,
      proctitis, and local skin reaction. These were equally distributed between the
      two groups. There was no significant difference in overall and disease-free
      survival in the two groups.

PMID- 7522204
TI  - A novel biological aspect of ovarian oxytocin: oxytocin gene expression in
      cumulus/luteal cells and the effect of oxytocin on embryogenesis in fertilized
      oocytes.
AB  - Recently, several reports have demonstrated the presence of oxytocin (OT) in the
      corpus luteum of mammalian species. However, the biological role of ovarian OT
      remains obscure. This study was performed to examine OT gene expression in
      cumulus cells of mice and humans, and in human corpus luteum, and the role of OT
      in early embryogenesis. OT gene and OT mRNA were analyzed by reverse
      transcription-polymerase chain reaction, with single-strand-conformation
      polymorphism and heteroduplex procedures. OT-treated in-vitro-fertilized mouse
      oocytes were cultured and the rate of blastocyst development estimated. An
      immunohistochemical study was also carried out to detect OT on the surface of the
      mouse oocytes.

PMID- 7522202
TI  - Recurrent ovarian sex cord tumor with annular tubules: tumor marker and
      chemotherapy experience.
AB  - Recurrent sex cord tumor with annular tubules is an unusual ovarian cancer. The
      authors report a patient with recurrent disease that was ultimately followed with
      multiple tumor markers. During this period the patient was treated only with
      chemotherapy. Her regimen consisted of a combination of etoposide, bleomycin, and
      cisplatin. The tumor markers that were followed were CA-125, CEA, inhibin, and
      Mullerian-inhibiting substance (MIS). There was no elevation of the CA-125 or
      CEA, but inhibin and MIS proved to be effective markers. Serum inhibin and MIS
      correlated perfectly with her documented disease status and was brought into the
      normal range when the patient was disease-free. This disease-free status was
      proven by surgical reexploration. This report is the first documented complete
      response in this rare malignancy treated by chemotherapy alone with distant
      metastatic spread. It also gives strong linkage of inhibin and MIS as good
      markers in this particularly rare malignancy.

PMID- 7522205
TI  - Expression of epidermal growth factor and transforming growth factor-alpha in
      fallopian tube epithelium and their role in embryogenesis.
AB  - We studied the expression of epidermal growth factor (EGF) and transforming
      growth factor (TGF)-alpha in human fallopian tube epithelium at various menstrual
      stages. Immunohistochemical staining using anti-EGF and anti-TGF-alpha antibodies
      showed a specific staining in ampullary tube epithelium at late follicular and
      luteal stages but the staining was very weak at the early follicular stage.
      Quantitative reverse transcription and polymerase chain reaction (RT-PCR) using
      beta-actin mRNA as an internal standard revealed the menstrual-stage-specific
      expression of EGF and TGF-alpha gene transcripts: amounts of EGF and TGF-alpha
      mRNA relative to those of beta-actin were significantly higher at late follicular
      and luteal stages than at the early follicular stage. To clarify the biological
      role of these growth factors, mouse 2-cell embryos were cocultured with human
      fallopian tube epithelial cells with or without blocking the action of these
      growth factors. Cocultures significantly promoted blastocyst formation, but this
      promotive effect of the tubal epithelial cells was completely abolished by the
      addition of anti-EGF and/or anti-TGF-alpha monoclonal neutralizing antibodies to
      the coculture system. These results demonstrated that EGF and TGF-alpha were
      synthesized and expressed in fallopian tube epithelium at specific menstrual
      stages, and may be involved in early embryonic development.

PMID- 7522207
TI  - Implications of investigating the structure-function relationship of human growth
      hormone in clinical diagnosis and therapy.
AB  - Human growth hormone (GH) mediates longitudinal bone growth and also exerts a
      variety of other biological effects, e.g. lactogenic, insulin-like, diabetogenic,
      lipolytic, protein-anabolic and sodium/water-retaining effects. Investigation of
      the structure-function relationship of human GH has been attempted by epitope
      mapping using monoclonal antibodies and by systematic point mutations of the
      human GH molecule. The diagnosis of GH-related disorders is complicated by the
      fact that different commercial immunoassay kits give widely differing results.
      This phenomenon cannot be explained by lack of standardization, but has to be
      attributed to the epitope specificities of the antibodies employed in the assay
      techniques and the spectra of different molecular forms of human GH recognized by
      them. The information required by a clinician in ordering a GH determination is
      the bioactivity of all the human GH forms in the sample, rather than the
      immunoreactivity with a given set of antibodies. Therefore, the aim of future GH
      immunoassays must be the identification of antibodies that bind with high
      affinity only those forms of human GH that bind and activate the GH receptor.
      Epitope mapping by monoclonal antibodies appears to be the ideal approach to this
      goal. It has recently been shown that one molecule of human GH binds two
      molecules of GH receptor, and dimerization of the receptor by its ligand is a
      prerequisite for biological function. Improvements in understanding the structure
      function relationship of the human GH molecule and of the interplay of the
      hormone with its receptor make it conceivable that recombinant analogues of human
      GH will be designed to inhibit the effects of GH excess in acromegaly.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7522208
TI  - Analysis of the interaction of insulin-like growth factor I (IGF-I) analogs with
      the IGF-I receptor and IGF-binding proteins.
AB  - Analogs of insulin-like growth factor I (IGF-I) have been prepared by site
      directed mutagenesis in order to determine the structural domains of IGF-I
      required for IGF receptor and IGF-binding protein (IGFBP) binding, and to produce
      analogs with selective affinity for receptors or IGFBP to determine the
      physiologic roles of these proteins. Distinct domains of IGF-I are important for
      maintaining high affinity for the IGF-I receptor and for the various species of
      IGFBPs. The analogs that selectively bind to the receptor and have reduced
      affinity for IGFBPs have proved useful in determining the relative importance of
      IGFBPs in the regulation of the biologic activity of IGF-I. In most cases,
      analogs with reduced affinity for IGFBP have increased or normal potency compared
      with IGF-I. These data suggest that binding of IGF-I to IGFBP inhibits its
      biologic activity. As these analogs are cleared more rapidly after parenteral
      administration, however, they do not provide a significant advantage over IGF-I
      for in vivo administration. Analogs with poor affinity for the receptor have also
      been useful in demonstrating that a given activity of IGF-I is mediated by the
      type 1 IGF receptor. These studies confirm that the role of these various
      proteins in IGF-I action is complex, and may be cell specific or tissue-type
      specific.

PMID- 7522206
TI  - Phosphofructokinase activity as a measure of maturation of rat oocytes developed
      in vivo and in vitro.
AB  - We determined the activity of phosphofructokinase (PFK), a rate-limiting enzyme
      of glycolysis, in the rat oocyte during maturation either by luteinizing hormone
      stimulation in vivo or by cultivation under various conditions. In vivo, the
      activity of PFK in the maturing oocyte increased significantly, suggesting that
      the glycolytic pathway developed as the first meiotic division proceeded. A
      breakdown of the germinal vesicle and an increased activity of PFK were observed
      when denuded oocytes were cultured. Treatment of the oocytes with dibutyryl cAMP
      and 3-isobutyl-1-methyl xanthine almost completely inhibited germinal breakdown,
      whereas the activity of PFK increased significantly. The data suggest that
      regulation of PFK activity is not directly dependent on cAMP or cAMP-dependent
      protein kinase, and is not necessarily dependent on meiotic maturation. Our study
      also revealed that epidermal growth factor (EGF) significantly increased PFK
      activity, showing that EGF may be a potent inducer of oocyte maturation.

PMID- 7522210
TI  - Mapping of the genes encoding human inducible and endothelial nitric oxide
      synthase (NOS2 and NOS3) to the pericentric region of chromosome 17 and to
      chromosome 7, respectively.
AB  - Nitric oxide (NO) is an important molecular messenger regulating the functions of
      a wide variety of cells and tissues. NO is synthesized from L-arginine by a
      variety of isoforms of the enzyme nitric oxide synthase (NOS). We have used
      Southern blotting analysis on DNAs obtained from a panel of human-rodent hybrid
      cell lines to map the gene encoding the inducible NOS (NOS2) to chromosome 17cen
      17q11 and the gene encoding the endothelial form of NOS (NOS3) to chromosome 7.
      Fluorescence in situ hybridization using a NOS2 probe gave several signals in the
      17p11-q11 pericentromeric region.

PMID- 7522211
TI  - Identification of eight mutations and three sequence variations in the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene.
AB  - To determine cystic fibrosis (CF) defects in a sample of 224 non-delta F508 CF
      chromosomes, we used denaturing gradient gel multiplex analysis of CF
      transmembrane conductance regulator gene segments, a strategy based on blind
      exhaustive analysis rather than a search for known mutations. This process
      allowed us to detect 11 novel variations comprising two nonsense mutations (Q890X
      and W1204X), a splice defect (405 + 4 A-->G), a frameshift (3293delA), four
      presumed missense mutations (S912L, H949Y, L1065P, Q1071P), and three sequence
      polymorphisms (R31C or 223 C/T, 3471 T/C, and T1220I or 3791 C/T). We describe
      these variations, together with the associated phenotype when defects on both CF
      chromosomes were identified.

PMID- 7522209
TI  - Expression of intercellular adhesion molecule-1 and vascular cell adhesion
      molecule-1 in undifferentiated nasopharyngeal carcinoma (lymphoepithelioma) and
      in malignant epithelial tumors.
AB  - Immunoreactivity for intercellular adhesion molecule-1 (ICAM-1) and for vascular
      cell adhesion molecule-1 (VCAM-1), two adhesion molecules of the immunoglobulin
      (Ig) superfamily, was tested and measured on tissue sections from 16
      undifferentiated nasopharyngeal carcinomas (U-NPC), 12 keratinizing squamous cell
      carcinomas (SCCs) of the head and neck region, and 54 malignant epithelial tumors
      of various origin. Neoplastic cells of all cases of U-NPC were diffusely and
      intensely stained for ICAM-1 and VCAM-1. Moreover, ICAM-1 messenger RNA (mRNA)
      and VCAM-1 mRNA were detected by Northern blot analysis of RNA extracts from two
      tumors. In the other epithelial tumors focal or diffuse staining for ICAM-1 was
      observed in 40 cases (66%), whereas reactivity for VCAM-1 was detected in a
      single case of metastatic undifferentiated carcinoma of unknown origin. The
      biopsy specimens of U-NPC showed variable infiltration by leukocytes, which were
      positive for the integrins lymphocyte function antigen-1 (LFA-1) and alpha-4/beta
      1, the corresponding ligands for ICAM-1 and VCAM-1. The possibility that ICAM-1
      and VCAM-1 on neoplastic cells may favor the intratumoral recruitment of
      leukocytes in a way similar to that occurring in crypt epithelium of the palatine
      tonsil is discussed.

PMID- 7522213
TI  - Functional studies on MEL-14+ and MEL-14- T cells in peripheral lymphoid tissues.
AB  - Functions of MEL-14+ T cells and MEL-14- T cells in peripheral lymphoid tissues
      were analyzed and compared. The MEL-14- T cells, representing a minor
      subpopulation of spleen and lymph node T cells, generated considerably higher
      mixed lymphocyte reaction and mitogen responses than the MEL-14+ T cells in any
      lymphoid tissues studied. Furthermore, upon stimulation with ConA the MEL-14-
      CD8+ T cells produced significantly larger amounts of IL-2 and IFN-gamma than MEL
      14+ CD8+ T cells did. A similar but less marked observation was obtained with the
      CD4+ T cell population. Furthermore, when B10.BR mice were immunized with AKR
      (Mls-1a) spleen cells, the proportion of the Mls-1a reactive V beta 6+ T cells
      from draining lymph nodes increased and a substantial proportion of the
      increasing V beta 6+ T cells was shown to be MEL-14-. The present findings on the
      whole indicate that MEL-14- T cells in the peripheral lymphoid tissues are at
      functionally high levels and may represent memory cells which have been
      previously stimulated in vivo.

PMID- 7522212
TI  - Immunological properties of heterozygous nu/+ mice: changes in antibody response
      and inducibility of tolerance to protein antigens.
AB  - Heterozygous nu/+ mice are not fully identical in their immunological properties
      with the mice of wild +/+ genotype. A colony of nu/nu, nu/+ and +/+ mice from the
      same breeding nucleus was established and their immune reactivity to human serum
      albumin, inducibility of adult immune tolerance to hen egg lysozyme (HEL),
      sensitivity of their lymphoid cells to stimulation by mitogens and ratio of CD3,
      CD4 and CD8 positive cell populations was studied. Both the numbers of antibody
      forming cells in regional lymph nodes and the antibody titres in sera of nu/+
      mice were highly variable, between undetectable values of nu/nu and high values
      of +/+ homozygotes. Intravenous pretreatment with soluble HEL, leading in +/+
      mice to a deep hyporeactivity to subsequent immunization with the same antigen,
      did not decrease the response of nu/+ mice significantly. These results indicate
      that the immunological alteration of nu/+ mice is not only quantitative and that
      T cell subpopulations might be differentially modified by the presence of nu
      allele. The finding of decreased CD4:CD8 ratio in nu/+ mice also supports this
      idea.

PMID- 7522214
TI  - Background immunoglobulin-secreting cells specific for intestinal peptidoglycan
      polysaccharides in mice.
AB  - Natural antibodies to soluble peptidoglycan-polysaccharide complexes (PPC) from
      the human intestinal flora have been found in mammalian sera. In this study the
      occurrence and frequency of PPC-specific immunoglobulin-secreting cells (anti-PPC
      Ig-SC) were determined in lymphoid organs of normal (C57BL x CBA)F1 mice. One out
      of 100 IgM-SC in the spleen and Peyer's patches was found to be specific for PPC.
      In the small intestine a small number of anti-PPC IgA-SC were present probably
      responsible for IgA secretion in the gut lumen since very low serum
      concentrations anti-PPC IgA were found. Anti-PPC IgG-SC were not detected,
      although some anti-PPC IgG was found in the serum. It is concluded that the
      spleen is the major lymphoid organ responsible for the production of natural
      antibodies to PPC.

PMID- 7522217
TI  - The major histocompatibility complex and peptide vaccines in domestic animals.
AB  - Three hypotheses are suggested to explain the phenomenon of low responsiveness in
      domestic animals after injection of peptide vaccines. The first hypothesis
      proposes involvement of MHC haplotype and the special case in livestock breeding,
      where inheritance of the sire's haplotype can be closely examined by injection of
      antigen into a large number of paternal half-sib progeny. The second hypothesis
      examines the effect of repeated antigen injections in overcoming age and MHC
      haplotype effects and distinguishing these effects from those caused by
      deficiencies in the T cell repertoire. The third hypothesis concerns non-MHC
      effects that influence the expression of MHC haplotype effects and enable the
      host to mount an effective immune response. It is suggested that the antigen
      recognition signal from T cell receptor/MHC interaction is amplified to a varying
      extent in animal populations. Deficiency in this amplification through myeloid
      cell or cytokine responses may be yet another factor limiting immune
      responsiveness.

PMID- 7522216
TI  - Upregulation of human neutrophil CD59, a regulator of the membrane attack complex
      of complement, following cell activation.
AB  - CD59 is a membrane glycoprotein that regulates the membrane attack complex of
      complement and protects cells from autologous complement damage. Human
      polymorphonuclear leucocyte (PMN) expression of CD59 was confirmed by flow
      cytometry following staining with mAb 1F5, and western blotting revealed staining
      of a 19-23 kDa band. Warming of PMN from 4 to 37 degrees C resulted in
      spontaneous CD59 upregulation. A dose-dependent increase in expression following
      PMN stimulation with FMLP was observed and occurred within minutes, indicating
      that new protein synthesis was not required. Treatment of PMN with calcium
      ionophore A23187 resulted in similar increases in CD59 expression. This occurred
      in the presence or absence of extracellular calcium, indicating that upregulation
      was dependent on release of calcium from intracellular stores. Evidence for a
      mobilizable intracellular pool of CD59 was obtained by detection of increased
      binding of 1F5 following PMN permeabilization; CD59 could also be re-expressed
      after stripping by phosphatidylinositol specific phospholipase C (PI-PLC) by
      treatment with FMLP or A23187. There was a correlation between CD59 upregulation
      and lactoferrin release, suggesting that stores of CD59 may be associated with
      secondary granules. These studies indicate that PMN expression of CD59 is
      enhanced by cell activation and suggest the presence of an intracellular pool of
      CD59 which can be translocated to the cell membrane upon PMN stimulation.

PMID- 7522215
TI  - Identification of a Mycobacterium leprae-specific T cell epitope on the 70 kDa
      heat shock protein.
AB  - A major antigen of the leprosy bacillus, Mycobacterium leprae, is the 70 kDa heat
      shock protein (Hsp70), which has significant sequence homology with Hsp70 from
      other mycobacterial species as well as Hsp70 from eukaryotes. A unique region of
      70 amino acids at the C-terminus of the M. leprae Hsp70 has been previously
      identified. This study investigated whether mice immunized with the C-terminal
      fragment of M. leprae Hsp70 recognize T cell epitopes in this species-specific
      portion of the molecule. Murine lymphoproliferative responses to overlapping
      peptides spanning the C-terminal 70 amino acids were restricted to mice of an H
      2b haplotype and identified the presence of a determinant in sequence 567-591.
      Lymph node cells from mice immunized with this peptide recognized both the C
      terminal fragment and the whole Hsp70 molecule. Moreover, mice immunized with the
      same peptide responded to the whole Hsp70 molecule in a delayed-type
      hypersensitivity reaction. The significance of M. leprae-specific T cell epitopes
      in the host response to mycobacterial infection is discussed.

PMID- 7522218
TI  - Electrochromatography: a method for automatic immunoaffinity chromatography on
      porous membranes.
AB  - Electrochromatography (ECHR) exploits a very high electro-osmotic counterflow
      developed in porous membranes at discontinuous electrophoresis. This counterflow
      exceeds considerably the anodic migration of any negatively charged protein and
      is used as a 'conveyer belt' for sequential transfer of immunoreagents to the
      specific adsorbents (antigens or antibodies) fixed on the nitrocellulose
      membrane. This approach was applied for simultaneous detection of two antigens
      (alpha-fetoprotein and carcino-embryonic antigen) in one sample, for
      determination of subfractions of alpha-fetoprotein, different in their epitope
      specificity, and for detection of L chains with certain idiotype on the
      background of heterogeneous L fraction. ECHR was used also for the partition of
      different antibodies to DNA adducts, demonstrating the possibility of applying
      this method to the study of DNA-binding proteins.

PMID- 7522219
TI  - Differential effects of serum on lipopolysaccharide receptor-directed macrophage
      activation for nitric oxide production.
AB  - In this manuscript, the effects of fetal bovine serum (FBS) on activation of
      mouse macrophages through the p73 lipopolysaccharide (LPS) receptor have been
      evaluated. In confirmation of earlier published studies, FBS will significantly
      potentiate the ability of LPS to activate macrophages to produce nitric oxide
      (NO). Evidence that this potentiating effect of FBS is mediated primarily by an
      interaction with LPS is provided by data showing that the stimulating effects of
      a hamster IgM monoclonal antibody to the p73 LPS receptor are significantly
      suppressed under identical conditions of FBS addition. The presence of FBS
      enhances both the kinetics of LPS-induced NO production and delays the induction
      of MAb5D3-induced NO production. The data establish that the ability of FBS to
      reduce MAb5D3-initiated NO production can only be manifest during the first 4-6 h
      following activation with antibody. Similarly, the ability of polymyxin B (which
      does not affect MAb5D3 activity) to inhibit LPS-dependent macrophage activation
      is also only effective during the first 4-6 h of stimulation, suggesting a
      parallel kinetic profile in the activation of the inducible NO synthase by these
      related activators. These studies provide data which suggest a dual role for
      serum factors in LPS-dependent macrophage activation, a direct effect of FBS on
      LPS which potentiates its immunostimulatory activity, and a secondary down
      regulation effect which is manifest at the level of the macrophage.

PMID- 7522221
TI  - Tumor marker studies of cervical smears: an immunohistochemical approach.
AB  - Immunoreactivity with monoclonal antibodies against epithelial membrane antigen
      (EMA), vimentin, squamous epithelium-specific keratin, nonsquamous epithelium
      specific keratin, and polyclonal antibodies epithelial cells of 55 cervical
      smears using the avidin-biotin-peroxidase complex and indirect immunoperoxidase
      methods to detect antigens. Most of the abnormal squamous cells with few normal
      cells were reactive for EMA but the intensity of the reaction was variable in
      both cases. There was no correlation in the reactivity between normal and
      abnormal cells with different cytokeratins varying in their molecular weight.
      Vimentin was also reactive with both cells. The results of this experiment
      suggest that antibodies used, appear to be of limited usefulness in the diagnosis
      of cervical smears.

PMID- 7522220
TI  - Functional analysis of Mel-14+ and Mel-14- early precursor cells in the adult
      mouse thymus.
AB  - The earliest T-cell precursor population in the adult mouse thymus (low CD4
      precursors) may be divided into 85% of cells expressing surface Mel-14 (LECAM-1,
      the lymphocyte homing receptor) and 15% of cells which are Mel-14. To date, this
      is the only surface marker for which we have found this population to be
      heterogeneous. The precursor activity of the Mel-14+ and Mel-14- subpopulation
      was assessed by both intrathymic and intravenous transfer of sorted cells into
      Ly5 congenic irradiated recipient mice. On both a cell-for-cell and a total
      activity basis, almost all precursor activity was associated with the Mel-14+
      cells. No segregation was seen between T-cell, B-cell and dendritic cell
      precursor activity of the low CD4 population, all activities being concentrated
      in the Mel-14+ fraction. This strengthens the hypothesis that one precursor cell
      has the potential to form all three lineages.

PMID- 7522222
TI  - Choroid plexus tumours--an immunohistochemical analysis with review of
      literature.
AB  - Immunohistochemical analysis of 9 choroid plexus papillomas (CPPs) and 3 choroid
      plexus carcinomas (CPCs) using a panel of antibodies against glial fibrillary
      acidic protein (GFAP), cytokeratin (CK), epithelial membrane antigen (EMA), S-100
      protein, vimentin (vim), and neuron specific enolase (NSE) is presented. Focal
      positivity was observed for GFAP in 11, vimentin in 7, cytokeratin in 2 and EMA
      in 3 cases. Diffuse and intense immunoreactivity for S-100 protein was seen in
      all papillomas, however, unreactive areas were noted in carcinomas. All cases
      exhibited focal to diffuse NSE positivity. Location and type of the tumour and
      age of the patient did not influence the staining pattern except for predominant
      S-100 positivity in papillomas. The significance of these findings is discussed
      in relation to the differential diagnosis or immunoreactivity patterns of these
      tumours.

PMID- 7522223
TI  - Modulation of carrageenan-induced hind paw edema by substance P.
AB  - Substance P has been implicated as a mediator of inflammation. The involvement of
      this neuropeptide in carrageenan-induced hind paw edema in the rat was assessed.
      Subcutaneous injection of carrageenan into the rat paw caused a significant
      increase in substance P levels, which preceded the onset of inflammation. While
      injection of substance P alone caused mild edema, coadministration of submaximal
      doses of carrageenan and substance P resulted in a synergistic exacerbation in
      the degree of inflammation. This synergistic response was not detected when the
      nonamidated precursor of substance P was coinjected with carrageenan. The effects
      of substance P depletion on inflammation were also evaluated. In animals
      pretreated with capsaicin followed by injection with carrageenan, no significant
      increase in either the levels of substance P or the extent of edema was observed
      when compared to capsaicin-treated controls. These results indicate that
      substance P may play an important role in the early stages of carrageenan-induced
      paw edema and that a reduction in the biosynthesis of substance P may lessen the
      severity of this inflammatory response.

PMID- 7522224
TI  - Serum viscosity is a sensitive test for monitoring primary Sjogren syndrome.
AB  - Primary Sjogren's syndrome (pSS) is characterized by chronic inflammation,
      resulting in secondary changes in serum protein content. In an attempt to
      evaluate disease activity we have measured serum viscosity (SV) in 41 patients
      with pSS and compared SV with laboratory findings such as: total proteins, gamma
      globulin concentrations, titre of rheumatoid factor (RF) and level of circulating
      immune complexes. SV was found to correlate with these laboratory parameters. The
      pSS patients with low serum viscosity had worse clinical abnormalities than those
      with the high SV. Thus SV affords a useful monitoring test for pSS patients.

PMID- 7522225
TI  - Is vertebrate phototransduction solved? New insights into the molecular mechanism
      of phototransduction.

PMID- 7522227
TI  - Low mature TGF-beta 2 levels in aqueous humor during uveitis.
AB  - PURPOSE: To investigate whether transforming growth factor-beta 2 (TGF-beta 2), a
      strong immunosuppressive factor normally present in aqueous humor, is involved in
      the inflammatory process of clinical uveitis. METHODS: Mature TGF-beta 2 levels
      were determined in aqueous humor samples of 9 patients with Fuchs' heterochromic
      cyclitis, aqueous humor samples of 21 patients with other uveitis entities, and
      vitreous fluid samples of 19 patients with uveitis by using a commercially
      available sandwich ELISA: Total TGF-beta 2 levels in ocular fluids were measured
      after heat activation. Aqueous humor samples from patients with cataract and
      glaucoma and vitreous fluid samples from eye bank eyes were tested as controls.
      Albumin levels, determined by radial immunodiffusion, were used as a measure of
      the disruption of the blood aqueous barrier. RESULTS: Significantly lower mature
      TGF-beta 2 levels were detected in aqueous humor samples of patients with
      uveitis, compared to the two control groups without intraocular inflammation.
      Samples of patients with uveitis without detectable mature TGF-beta 2 did contain
      latent TGF-beta 2 levels (504 to 6024 pg/ml). In aqueous humor, there was a
      significant negative correlation between mature TGF-beta 2 and albumin levels. No
      mature TGF-beta could be detected in vitreous fluid. Total TGF-beta 2 levels in
      vitreous fluid were significantly lower in samples from patients with uveitis
      than in samples from eye bank eyes. CONCLUSION: These results indicate that the
      mature TGF-beta 2 levels in aqueous humor and the total TGF-beta 2 levels in
      vitreous fluid are reduced during ocular inflammation. In aqueous humor, this
      might be caused by binding of mature TGF-beta to serum proteins, for instance,
      alpha 2-macroglobulin, or by a disturbance in the activation process of latent
      TGF-beta 2.

PMID- 7522226
TI  - The role of nitric oxide synthase in endotoxin-induced uveitis: effects of NG
      nitro L-arginine.
AB  - PURPOSE: To evaluate the role of nitric oxide synthase (NOS) in endotoxin-induced
      uveitis (EIU). METHODS: EIU was caused in Lewis rats by injecting
      lipopolysaccharide (LPS) into the foot pad, and the effects of an NOS inhibitor,
      NG-nitro L-arginine (NA), was comparatively studied by the simultaneous
      administration of NA and LPS. Total NOS and inducible NOS (iNOS) activities were
      differentially assayed in the anterior segment of the eye in EIU with and without
      NA treatment. The effects of NA on EIU were also evaluated by clinical
      manifestation, histology, and protein concentration in the aqueous humor.
      RESULTS: In untreated rats, there was no significant iNOS activity. With the EIU
      model, iNOS activity showed a marked increase in the anterior segment of the eye,
      reaching a maximum 9 hours after LPS injection (10,850 +/- 1,650 cpm/mg protein,
      mean +/- SEM). NA reduced the iNOS activity 9 hours after injection to 2,400 +/-
      90 cpm/mg protein (P < 0.001). Aqueous humor protein concentration in the EIU
      model was 10.6 +/- 0.75 mg/ml, and the cell number was 216 +/- 12
      cells/microliters. NA significantly reduced these factors to 4.25 +/- 0.48
      mg/microliters for the protein concentration (P < 0.0005) and 25 +/- 6 cells/ml
      for the cell number (P < 0.0005). Histologic studies showed less prominent
      infiltration of polymorphonuclear cells in the anterior uvea than for
      conventional EIU. CONCLUSIONS: Induction of iNOS may play a key role in the
      pathogenesis of EIU. Because inhibition of iNOS activity reduced the inflammatory
      response, suppression of NO formation may inhibit the development of EIU.

PMID- 7522231
TI  - Epitope mapping and functional characterization of monoclonal antibodies specific
      for the alpha subunit of Escherichia coli RNA polymerase.
AB  - The epitopes have been localized for a set of monoclonal antibodies specific for
      the alpha subunit of the Escherichia coli RNA polymerase. The antibodies are
      classified into three groups based on their epitopic assignments. Group 1, mAb
      123C2, maps in the N terminus of alpha between amino acids 1 and 23; Group 2
      antibodies (mAb 129C4, mAb 124D1 and mAb 121C5) map in the central region between
      amino acids 190 and 210; Group 3 antibodies (mAb 130B1 and mAb 125C6) map in the
      C terminus between amino acids 310 and 320. mAb 130C2 is anomalous since it maps
      to the N terminus between amino acids 1 and 23 as well as to the C terminus
      between amino acids 320 and 329. The antibodies were used to investigate the role
      of alpha in transcription activation with cAMP receptor protein-dependent
      promoters. Three antibodies (130C2, 121C5, and 125C6) inhibited cAMP receptor
      protein-dependent initiation with lac P+ but not with lac UV5 or gal P+.
      Inhibition was observed with free RNA polymerase and the closed promoter complex;
      the preformed open promoter complex was insensitive. Only lac P+ was sensitive to
      these anti-alpha antibodies supporting the concept that the mode of interaction
      of RNA polymerase with cAMP receptor protein differs between lac P+ and gal P+.

PMID- 7522230
TI  - Temporal regulation of non-transmembrane protein tyrosine kinase enzyme activity
      following T cell antigen receptor engagement.
AB  - We evaluated in Jurkat T cells the time-dependent responses of Fyn, Lck, Syk, and
      Zap following antibody-mediated cross-linking of the T cell antigen receptor. Our
      results show that the protein kinase activities of Fyn and Lck were activated
      within seconds of receptor cross-linking. Fyn activity, as measured by
      autophosphorylation and tyrosine phosphorylation of an exogenous substrate, was
      maximal 5 s to 1 min following receptor cross-linking. Lck was also found to be
      activated within 5 s of antigen receptor cross-linking but differed from Fyn in
      that Lck activity was elevated for at least 30 min. Syk and Zap protein kinase
      activities were found to peak between 5 and 10 min following receptor cross
      linking, returning to approximately basal activity levels by 60 min. The protein
      kinase activities of both Syk and Zap were found to parallel their reactivity in
      immunoblotting experiments with anti-phosphotyrosine antibodies. Both Syk and Zap
      were found to associate with the tyrosine-phosphorylated zeta subunit of the T
      cell antigen receptor. These observations imply that T cell antigen receptor
      signal transduction involves the activation of multiple members of at least two
      different families of non-transmembrane protein tyrosine kinases.

PMID- 7522228
TI  - Isolation of human aquaporin-CD gene.
AB  - The human gene encoding aquaporin-CD (AQP-CD) was isolated, and its structural
      organization was characterized. The gene appeared to exist as a single copy in
      the human genome and comprises four exons distributing over 5 kilobases. The size
      range of exons is 81-761 base pairs, and that for introns is approximately 3000
      to approximately 250 base pairs. The exon-intron boundaries of human AQP-CD gene
      are identified at identical positions in other related genes, the human AQP-CHIP
      gene and the human major intrinsic protein gene. The major transcription
      initiation sites were identified to positions 93 and 94 base pairs upstream of
      the ATG initiation codon by primer extension and ribonuclease protection assay.
      The 5'-flanking region of the hAQP-CD gene was characterized by a TATA box, two
      GATA consensus sequences, an AP-1 site, an AP-2 site, three E-boxes, and a cyclic
      AMP-responsive element. These structural features will lead to a better
      understanding of the mechanisms of tissue-specific expression and the regulation
      by dehydration in AQP-CD gene and will also be of help in search for possible
      genetic disorders in human AQP-CD gene.

PMID- 7522229
TI  - Modification of glycoproteins by N-acetylglucosaminyltransferase V is greatly
      influenced by accessibility of the enzyme to oligosaccharide acceptors.
AB  - The formation of tri- and tetraantennary complex-type N-linked oligosaccharides
      in animal glycoproteins is partly regulated by UDP-N-acetylglucosamine:beta-6-D
      mannoside beta-1,6-N-acetylglucosaminyltransferase (EC 2.4.1.155) (GlcNAc-T V),
      which generates 2,6-branched mannose. In Chinese hamster ovary (CHO) cells we
      found that 2,6-branched mannosyl structures are preferentially contained on
      lysosome-associated membrane proteins (LAMPs) and are generally low or absent in
      other cellular glycoproteins (Do, K.-Y. and Cummings, R.D. (1993) J. Biol. Chem.
      268, 22028-22035). To determine the mechanism by which GlcNAc-T V appears to
      preferentially recognize glycoproteins, we examined the activity of purified
      GlcNAc-T V toward a variety of glycoprotein acceptors. Because GlcNAc-T V
      requires as acceptors oligosaccharides lacking outer galactosyl and sialyl
      residues, we utilized two classes of acceptor preparations. The first class of
      acceptor was enzymatically desialylated (DS) and degalactosylated (DG)
      preparations of bovine fetuin, human transferrin, and human fibrinogen. The
      second class was glycoproteins in extracts of the mutant CHO cell line, Lec8 CHO,
      which cannot add galactose or sialic acid to N-linked oligosaccharides. GlcNAc-T
      V was highly active toward DSDG-fetuin, -transferrin, and -fibrinogen (Km values
      ranged between 30 and 74 microM), and the catalytic efficiencies (Vmax/Km) of the
      enzyme toward different acceptors were comparable. In the case of fetuin, each of
      its three sites for attachment of N-linked oligosaccharides were shown to be
      utilized equally well by GlcNAc-T V. Notably, the enzyme exhibited a 2-3-fold
      higher rate of transfer toward DSDG-transferrin when it was further denatured by
      reduction and S-carboxymethylation. When extracts of Lec8 CHO cells were used as
      acceptors, GlcNAc-T V preferentially transferred to LAMPs, and only low level
      transfer was observed to other cell-derived glycoproteins, thus demonstrating
      specificity of GlcNAc-T V toward native glycoprotein acceptors. When the cell
      derived glycoproteins were denatured by reduction and S-carboxymethylation prior
      to use as acceptors for Glc-NAc-T V, significant transfer occurred to other
      glycoproteins. These results demonstrate that the mechanism of glycoprotein
      specific branching by GlcNAc-T V is determined primarily by its accessibility to
      available bi/triantennary oligosaccharides on glycoproteins and not by its
      recognition of peptide determinants or conformation-specific determinants.

PMID- 7522232
TI  - Alternatively spliced isoform of P-selectin is present in vivo as a soluble
      molecule.
AB  - To demonstrate the presence of a soluble isoform of P-selectin predicted from
      cDNA sequencing (Johnston, G.I., Bliss, G.A., Newman, P.J., and McEver, R.P.
      (1990) J. Biol. Chem. 265, 21381-21385), we immunoisolated and compared
      structurally P-selectin from fresh frozen human plasma with that from washed
      intact platelets. Plasma P-selectin was reactive with rabbit antiserum to a
      synthesized peptide (residues 762-774 of mature P-selectin) but was significantly
      less reactive with antibody to a peptide (residues 747-760). In contrast,
      platelet P-selectin reacted with both antibodies. S-Pyridylethylated plasma P
      selectin was fractionated by reversed phase-high performance liquid
      chromatography into two major species. From platelets, two virtually identical
      species were separated. Sequential digestion with Achromobacter protease I and
      then Staphylococcus V8 protease produced peptides assigned to the tail region of
      the protein including the putative spliced site. From the more hydrophilic
      species in both plasma and platelets, a peptide completely lacking the sequence
      of the putative spliced site was identified. In contrast, the more hydrophobic
      species yielded a peptide with an intact transmembrane sequence. Hence, these
      results provide direct evidence that the previously predicted soluble isoform of
      P-selectin is actually synthesized in vivo and is present as a circulating
      molecule.

PMID- 7522233
TI  - Interleukin (IL)-3 and granulocyte/macrophage colony-stimulating factor, but not
      IL-4, induce tyrosine phosphorylation, activation, and association of SHPTP2 with
      Grb2 and phosphatidylinositol 3'-kinase.
AB  - Binding of interleukin (IL)-3 and granulocyte/macrophage colony-stimulating
      factor (GM-CSF) to their high affinity cell surface receptors induces tyrosine
      phosphorylation of a similar set of protein substrates. We have identified one of
      these common substrates (p70) as the protein-tyrosine phosphatase SHPTP2. The Src
      homology 2 (SH2) domain of the adaptor protein Grb2 bound with high affinity to
      tyrosine-phosphorylated SHPTP2 following treatment of cells with IL-3 or GM-CSF,
      but not IL-4. This interaction was inhibited by two phosphotyrosine peptides,
      based on sequences within SHPTP2, which conform to the postulated consensus
      sequence for Grb2 SH2 recognition. Following treatment with IL-3 or GM-CSF, but
      not IL-4, SHPTP2 co-immunoprecipitated with antibodies directed against the p85
      subunit of PI 3'-kinase. This was partially blocked by the same phosphopeptides
      that blocked Grb2-SH2 binding to SHPTP2. Importantly, treatment with IL-3
      resulted in a 2-3-fold increase in SHPTP2 phosphatase activity. These results
      suggest that SHPTP2 may play an important role in integrating signals from the IL
      3 and GM-CSF receptors to both Ras and PI 3'-kinase.

PMID- 7522234
TI  - Calcineurin-mediated protein dephosphorylation in brain nerve terminals regulates
      the release of glutamate.
AB  - In response to Ca2+ entry, several prominent brain nerve terminal phosphoproteins
      undergo dephosphorylation, but the relation between dephosphorylation and
      neurotransmitter release is unknown. Using the immunosuppressants cyclosporin A
      (CsA) and L-683,590 (FK-520) to inhibit specifically the Ca2+/calmodulin
      dependent protein phosphatase calcineurin, we demonstrate here that Ca(2+)
      dependent dephosphorylation in isolated rat brain nerve terminals (synaptosomes)
      is mediated by calcineurin. Pretreatment with micromolar CsA resulted in a 76-95%
      inhibition of stimulation-induced decreases in 32P-labeled dynamin (previously
      referred to as dephosphin), a phosphoprotein of M(r) = 145,000 (145-kDa protein),
      and a phosphoprotein of M(r) = 170,000 (170-kDa protein). Pretreatment with FK
      520 also inhibited Ca(2+)-dependent dephosphorylation. Using hypotonic lysates of
      32P-labeled synaptosomes, the addition of Ca2+ plus calmodulin, but not either
      agent alone, induced dynamin dephosphorylation. CsA and FK-520 had little to no
      effect on the release of glutamate induced by either K(+)-depolarization or the
      Ca2+ ionophore ionomycin. In contrast, calcineurin inhibition led to a
      substantial enhancement of glutamate release evoked by the K(+)-channel blocker 4
      aminopyridine, an agent whose action most closely mimics physiological
      stimulation. Calcineurin inhibition had no effect on stimulation-induced changes
      in synaptosomal Ca2+ levels. Based on our findings, we hypothesize that Ca(2+)
      dependent protein dephosphorylation resulting from calcineurin activation during
      physiological stimulation limits neurotransmitter release from brain nerve
      terminals, perhaps being dependent upon cyclic repolarization of the membrane
      during stimulation.

PMID- 7522235
TI  - Relative topography of biologically active domains of human vitronectin. Evidence
      from monoclonal antibody epitope and denaturation studies.
AB  - A panel of monoclonal antibodies to human vitronectin was used to define some
      epitopes for the multifunctions of this protein. Separate antibodies were
      identified which strongly inhibited cell spreading activity and which prevented
      binding to collagen. A third group interfered with the ability of vitronectin to
      inhibit complement-mediated guinea pig erythrocyte reactive lysis. None of the
      antibodies from these three groups prevented heparin binding, providing evidence
      that this reaction occurs at a fourth location; a different monoclonal antibody
      partially inhibited the binding of heparin. The relative accessibility of each
      biologically active epitope was assessed by the differential binding of the
      monoclonals to native and denatured vitronectin. Reactivity of the antibody which
      inhibited heparin binding greatly increased upon denaturation of vitronectin,
      implying that this region is normally inaccessible in the native form of the
      molecule. By contrast, epitopes for cell spreading, collagen binding, and
      inhibition of terminal complement complex lysis were destroyed by denaturation.
      On the basis of denaturation data and epitope mapping by competitive exclusion of
      monoclonal antibodies, a Venn diagram was constructed to represent overlap of
      monoclonal antibody epitopes in the tertiary structure. Linear epitopes for the
      antibodies were identified using cyanogen bromide and plasmin-derived peptides
      from vitronectin. The antibody which strongly inhibited cell binding reacted with
      a region containing the RGD site, whereas linear epitopes for collagen binding
      and complement inhibition appeared to reside in a 43-kDa peptide representing the
      internal region of the amino acid sequence, excluding the heparin-binding site.
      The latter two epitopes were differentiated from each other by reactivity of the
      antibody which inhibited collagen binding toward a smaller 20-kDa plasmin-derived
      peptide.

PMID- 7522236
TI  - Methylation status and chromatin structure of an early response gene (ornithine
      decarboxylase) in resting and stimulated NIH-3T3 fibroblasts.
AB  - The early response gene ornithine decarboxylase (odc) is indispensable for normal
      and malignant cell growth. Although DNA methylation is generally associated with
      chromatin condensation and gene inactivation, the odc gene is heavily methylated
      at CCGG-sequences in animal cell lines. In this work we analyzed the chromatin
      structure and the DNA methylation status at the CpG-rich promoter sequences at
      the odc locus in mouse 3T3 fibroblasts. We show that the proximal promoter region
      of the odc locus is not hypermethylated, while the distal promoter sequences
      appear to have a few methylated CCGG-sites and display methylation polymorphism.
      Furthermore, it was found that the 5' promoter region of odc is constitutively
      more sensitive to micrococcal nuclease than the coding and 3' regions of the odc
      gene. Stimulation of the cells with serum resulted in an appearance of a DNase I
      sensitive site at the promoter region. The chromatin structure of the mid-coding
      and 3' regions of the odc gene also underwent structural changes that were
      accompanied by the rapid accumulation of odc mRNA. Such changes were not detected
      in the chromatin structure of glyceraldehyde-3-phosphate dehydrogenase (gadph)
      gene, whose expression remains invariant upon serum stimulation. These data
      suggest that the chromatin structure may play an important role in the rapid
      transcriptional activation of odc and other immediate early genes during serum
      stimulation.

PMID- 7522237
TI  - Staining pattern of type IV collagen and prognosis in early stage adenocarcinoma
      of the lung.
AB  - AIMS: To examine the prognostic value of basement membrane expression in early
      stage adenocarcinoma of the lung. METHODS: Using antibodies to type IV collagen,
      basement membrane expression at the tumour-stromal border was
      immunohistochemically analysed in 30 patients with early stage adenocarcinoma of
      the lung (pstage I and pstage II). Two patterns of staining for type IV collagen
      were observed: in the first one the staining line was conserved or partially
      fragmented; in the second the staining line was widely fragmented or absent in
      more than 10% of the tumour area. The first staining pattern was categorised as
      continuous and the second as discontinuous. RESULTS: Of the 24 patients with
      pstage I adenocarcinoma, 12 (50%) cases showed a continuous pattern. In only one
      (16.7%) of the six patients with pstage II adenocarcinoma was this pattern
      evident. Five year survival was greater in pstage I adenocarcinoma (65%) than in
      pstage II adenocarcinoma (17%), but the difference was not significant. When the
      analysis was restricted to the 24 patients with pstage I adenocarcinoma, five
      year survival was better in continuous pattern cases (88%) than in discontinuous
      pattern cases (20.5%) (p < 0.05). The survival curve of 12 patients with pstage I
      adenocarcinoma and a discontinuous pattern resembled that of the six patients
      with pstage II adenocarcinoma. CONCLUSION: These findings suggest that patients
      with pstage I adenocarcinoma and a discontinuous pattern have histopathologically
      unrecognised micrometastasis when they come to surgery. The staining pattern of
      type IV collagen could help in the prognosis of pstage I adenocarcinoma of the
      lung after surgery.

PMID- 7522238
TI  - Upregulation of ICAM-I by Plasmodium falciparum: in vitro and in vivo studies.
AB  - AIMS: To monitor the expression of intercellular adhesion molecule I (ICAM-I) in
      vitro after stimulation of human macrophages with Plasmodium falciparum antigens,
      as well as the plasma concentrations of soluble ICAM-I (SICAM-I) in vivo in
      malarial patients. METHODS: Human mononuclear leucocytes were cultured and
      stimulated for four hours with 300 ng/ml exogenous P falciparum antigens. CD14
      and CD54 (ICAM-I) expression was monitored using flow cytometry. Soluble ICAM-I
      (s ICAM-I) was also measured in the blood of 122 outpatients with malaria before
      and after treatment (Rio Branco, Acre, Brazil). RESULTS: ICAM-I expression
      increased from 15% to 375% after four hours of stimulation. When sICAM-I was
      analysed in the plasma of 122 patients with P falciparum or Plasmodium vivax
      malaria by enzyme immunoassay, significant increases were found. These were more
      pronounced in patients with P falciparum malaria, compared with healthy controls,
      and with the same patients four weeks after treatment. CONCLUSION: ICAM-I
      expression may also be upregulated in human macrophages by exogenous Plasmodium
      antigens as well as by cytokines during the acute phase of malaria. sICAM-I
      concentrations are downregulated after treatment, probably caused by the absence
      of circulating Plasmodium antigens.

PMID- 7522239
TI  - Orthostatic hypotension in patients, bed rest subjects, and astronauts.
AB  - Orthostatic hypotension after even short space flights has affected a significant
      number of astronauts. Given the need for astronauts to function at a high level
      of efficiency during and after their return from space, the application of
      pharmacologic and other treatments is strongly indicated. This report addresses
      the clinical problem of orthostatic hypotension and its treatments to ascertain
      whether pharmacologic or physiologic treatment may be useful in the prevention of
      orthostatic hypotension associated with space flight. Treatment of orthostatic
      hypotension in patients now includes increasing intravascular volume with high
      sodium intake and mineralocorticoids, or increasing vascular resistance through
      the use of drugs to stimulate alpha or block beta vascular receptors. Earlier
      treatment used oral sympathomimetic ephedrine hydrochloride alone or with "head
      up" bed rest. Then long-acting adrenocortical steroid desoxycorticosterone
      preparations with high-salt diets were used to expand volume. Fludrocortisone was
      shown to prevent the orthostatic drop in blood pressure. The combination of the
      sympathomimetic amine hydroxyamphetamine and a monoamine oxidase inhibitor
      tranylcypromine has been used, as has indomethacin alone. Davies et al. used
      mineralocorticoids at low doses concomitantly with alpha-agonists to increase
      vasoconstrictor action. Schirger et al used tranylcypromine and methylphenidate
      with or without a Jobst elastic leotard garment or the alpha-adrenergic agonist
      midodrine (which stimulates both arterial and venous systems without direct
      central nervous system or cardiac effects). Vernikos et al established that the
      combination of fludrocortisone, dextroamphetamine, and atropine exhibited a
      beneficial effect on orthostatic hypotension induced by 7-day 6 degrees head-down
      bed rest (a model used to simulate the weightlessness of space flight). Thus,
      there are numerous drugs that, in combination with mechanical techniques,
      including lower body negative pressure to elevate transmural pressure, could be
      studied to treat orthostatic hypotension after space flight.

PMID- 7522241
TI  - Neuronal nitric oxide synthase is localized in extrinsic nerves regulating
      perireceptor processes in the chemosensory nasal mucosae of rats and humans.
AB  - Nitric oxide synthase is the enzyme responsible for the production of the free
      radical gas nitric oxide, which has been implicated as an intercellular messenger
      in both the central and peripheral nervous systems. Immunoreactivity for nitric
      oxide synthase is often coincident with the histochemical demonstration of NADPH
      diaphorase activity. Using an antibody to the neuronal form of nitric oxide
      synthase and a histochemical technique for NADPH-diaphorase, we have compared the
      localization of immunoreactivity and histochemical reaction product in the nasal
      mucosae of rats and humans. Immunoreactivity for neuronal nitric oxide synthase
      was localized in the extrinsic perivascular innervation of the olfactory and
      vomeronasal mucosae of rats and in the olfactory mucosa of humans. In the rat
      nasal mucosa, specific groups of glands were also innervated; the density of
      nitrinergic innervation varied among them, with vomeronasal glands and posterior
      glands of the nasal septum being the most densely innervated. In contrast, NADPH
      diaphorase activity was present in olfactory, vomeronasal, and septal organ
      receptor neurons in rats and in olfactory receptor neurons in humans as well as
      in numerous nerve fibers, glands, and surface epithelial cells. The localization
      of neuronal nitric oxide synthase in extrinsic perivascular and periglandular
      nerve fibers suggests that nitric oxide may modulate the perireceptor processes
      of local blood flow and mucus secretion that influence the access to and
      clearance of chemical stimuli from rat and human chemosensory mucosae.

PMID- 7522240
TI  - A comparison of postspace-flight orthostatic intolerance to vasovagal syncope and
      autonomic failure and the potential use of the alpha agonist midodrine for these
      conditions.
AB  - After space-flights of less than ten days, orthostatic hypotension upon reentry
      is characterized by plasma volume depletion that may lead to activation of the
      Bezold-Jarisch reflex which is also considered to be the mechanism of vasovagal
      (neurocardiogenic) syncope. For space-flight of longer duration, loss of
      cardiovascular reflex control may take precedence over volume depletion and thus
      may have similarities to the orthostatic hypotension seen in patients with
      autonomic failure secondary to basal ganglial disease and peripheral
      neuropathies. Midodrine is an alpha-one agonist that produces arterial and venous
      constriction and leads to a decrease in heart rate by baroreceptor reflexes. The
      efficacy of Midodrine in successfully treating orthostatic hypotension secondary
      to autonomic failure has been shown in clinical trials. Midodrine's ability to
      vasoconstrict without increasing heart rate suggests that it might be a useful
      treatment for vasovagal syncope since stimulation of the Bezold-Jarisch reflex
      would be less likely. For post-space flight orthostatic hypotension, midodrine
      may be a useful adjunctive treatment to the measures currently being used.

PMID- 7522242
TI  - Membranous lipodystrophy: secondary type.
AB  - BACKGROUND: A peculiar type of fat necrosis was noted in some patients with
      various skin diseases. OBJECTIVE: We attempted to develop a classification of
      membranous lipodystrophy combining the results of our study and a review of other
      articles. METHODS: Five cases of skin diseases with membranous lipodystrophy were
      studied and their clinical and histopathologic features were analyzed. Previous
      reports of similar findings were reviewed. RESULTS: Membranous lipodystrophic
      changes were noted in morphea profunda, lupus panniculitis, and factitial ulcer.
      Microcysts were formed by the coalescence of the destroyed fat cells and were
      lined by amorphous, eosinophilic material. Some of the linings had a crenelated
      appearance. Microgranules were found in the histiocytes and in the hyalinized
      collagen stroma. The linings and microgranules stained positively with periodic
      acid-Schiff, were resistant to diastase, and also stained with Sudan black B.
      CONCLUSION: We propose the use of the term secondary membranous lipodystrophy to
      describe the local subcutaneous membranous lipodystrophic change that occurs as a
      result of other skin diseases, in contrast to primary idiopathic membranous
      lipodystrophy, which occurs without any antecedent factors.

PMID- 7522244
TI  - Fetal skin-derived MHC class I+, MHC class II- dendritic cells stimulate MHC
      class I-restricted responses of unprimed CD8+ T cells.
AB  - Dendritic cells are very potent, if not the most effective, stimulator cells for
      the induction of primary T cell immune responses. We have established, from
      murine fetal skin, growth factor-dependent cell lines with a pronounced dendritic
      shape and a phenotype similar to that of fetal Langerhans cells (i.e., MHC class
      I+/II). Functionally, these lines induce a vigorous proliferation of allogeneic,
      but not syngeneic, CD8+ lymphocytes. T cell blasts thus generated are capable of
      lysing various target cells in an MHC class I-restricted fashion. Our contention
      that this skin cell-induced MHC class I-restricted activation of CD8+ lymphocytes
      occurs in the absence of CD4+ T cells is based on 1) the lack of FACS-detectable
      CD4+ T cells in the purified CD8+ T cell population, 2) the lack of reactivity of
      purified CD4+ T cells to MHC class I-disparate fetal skin cell lines, and 3) the
      inhibition of the fetal skin cell-induced MLR by anti-CD8/MHC class I, but not
      anti-CD4/MHC class II, mAb. Skin cell-induced activation of unprimed CD8+ T cells
      was found to be critically dependent on physical contact between stimulator and
      responder cells and the expression of the costimulatory molecule B7 on fetal skin
      cell lines. Lines described in this study may represent a powerful tool for
      studying the molecular events occurring in the induction of MHC class I
      restricted primary immune responses, understanding their pathophysiologic role,
      and perhaps may prove useful for vaccination purposes against selected pathogens.

PMID- 7522243
TI  - Spontaneous production of granulocyte colony-stimulating factor in vitro by human
      B-lineage lymphocytes is a distinctive marker of germinal center cells.
AB  - The ability of human B lymphocytes to produce granulocyte (G)-CSF in vitro was
      investigated. Highly purified tonsillar B cells were fractionated into large and
      small cells by a Percoll density gradient, cultured, and tested for G-CSF gene
      expression. Large B cells spontaneous produced G-CSF mRNA and protein, whereas
      small B cells did not, even after incubation with various stimuli.
      Immunophenotypic analyses showed that large B lymphocytes contained approximately
      60 to 70% of cells with the characteristic surface markers of germinal center
      (GC) B cells (CD38+, CD10+, and surface IgG+). The remaining cells expressed
      CD39, CD23, and surface IgD and were presumably in vivo-activated follicular
      mantle zone B cells. Fractionation of the large B lymphocytes into CD39+, surface
      IgD+, and CD39-, surface IgD- cells showed that the latter, but not the former,
      cell type produced G-CSF spontaneously in culture. Stimulation of purified (CD39
      , surface IgD-) GC B cells with a CD40 mAb alone or in combination with IL-4
      increased G-CSF production. Because these stimuli rescued a large fraction of GC
      cells (up to 50%) from spontaneous apoptosis in vitro, the finding may suggest
      that prevention of apoptotic death resulted in an increased G-CSF production or
      that CD40 mab and/or IL-4 increased G-CSF gene expression in G-CSF-producing GC B
      cells. Malignant B cells purified from the invaded lymph nodes of three patients
      with follicular center cell lymphoma and three Burkitt lymphoma cell lines, which
      had an immunophenotype identical with that of normal GC B cells, spontaneously
      produced G-CSF in vitro, thus confirming the GC origin of the cytokine.
      Incubation of normal purified GC B cells with rG-CSF resulted in the rescue of GC
      B cells from apoptosis, suggesting that G-CSF may be used by GC B cells in an
      autocrine manner. This autocrine loop of production and response to G-CSF by GC B
      cells may be activated by stimuli such as those delivered via the surface CD40
      molecule, that participate in the rescue of GC B cells from apoptosis.

PMID- 7522245
TI  - gp120 ligation of CD4 induces p56lck activation and TCR desensitization
      independent of TCR tyrosine phosphorylation.
AB  - HIV gp120 binding to CD4 suppresses TCR function. The molecular mechanism of this
      anergizing effect is incompletely understood. Studies reported here reveal that
      CD4 ligation initiates p56lck activation and renders human peripheral T cells and
      HPB-ALL cells hyporesponsive to Ag receptor stimulation, as indicated by the
      failure of TCR binding ligands to induce either protein tyrosine phosphorylation
      or elevation of intracellular-free calcium concentration. To approach the
      possibility that p56lck-mediated tyrosine phosphorylation of specific sites
      within TCR zeta-chain might be involved in the gp120-induced TCR signaling
      defect, we tested the kinase's ability to phosphorylate various zeta peptides.
      Kinetics analyses indicate that peptides derived from the in vitro
      autophosphorylation site of p56lck Y394 and two sites within zeta, Y84, and Y152,
      are equally effective substrates for p56lck, whereas p56fyn prefers a substrate
      peptide derived from a different site within zeta, Y142. Although these data are
      consistent with the possibility that gp120-mediated signal disruption of TCR
      could be due to p56lck phosphorylation of Y84 and Y152 residues within zeta,
      further experiments revealed that gp120 does not induce detectable zeta tyrosine
      phosphorylation under conditions in which it disrupts TCR signaling. These data
      indicate that gp120 can induce uncoupling of TCR from the earliest events in
      signal transduction and that this effect can be mediated by a mechanism other
      than tyrosine phosphorylation of TCR zeta-chain.

PMID- 7522246
TI  - Activation and proliferation of follicular dendritic cell-like cells by activated
      T lymphocytes.
AB  - Follicular dendritic cell (FDC)-like cell lines (HK cells) from human tonsils
      were established to investigate the functional role of FDC in the germinal
      centers of lymphoid follicles. Although HK cells exhibited CD21, CD23, DRC-1,
      CD40, VCAM-1, ICAM-1, and HJ2 that were expressed on human tonsilar FDC at early
      stages of establishment, they lost DRC-1, CD21, and CD23 within 3 days of
      culture. Morphologic and functional characterization studies suggest that HK
      cells are quite distinct from fibroblasts. The growth requirement of HK cells is
      different from the previously reported FDC-like cell lines. Functionally, these
      cells bound B cells but not T cells, and supported B cell proliferation. The
      culture supernatants of HK cells had costimulatory activity on the proliferation
      of anti-mu- or anti-CD40-activated B cells, and the activity dramatically
      increased after 12-O-tetradecanoylphorbol 13-acetate stimulation. Interestingly,
      anti-CD3 Ab activated T cell bound to HK cells, inducing the phenotypic changes
      and the growth of HK cells. The T-HK cell interactions not only involve the well
      known adhesion ligand/receptor pathways (VLA-4/VCAM-1 and LFA-1/ICAM-1), but also
      involve CD40-CD40 ligand as shown by inhibitory effect of soluble CD40 (CD40.Fc).
      The cellular interactions between T and HK cells and cytokine production suggest
      that activated T cells not only stimulate resting B cells directly, but also
      support B cell maturation indirectly by stimulating the development of FDC. Hence
      HK cells may be useful in identifying the surface molecules and cytokines of FDC
      involved in the GC formation.

PMID- 7522249
TI  - Characterization of peptide binding to the murine MHC class I H-2Kk molecule.
      Sequencing of the bound peptides and direct binding of synthetic peptides to
      isolated class I molecules.
AB  - Peptides that are bound by the murine class I MHC molecule H-2Kk have been
      isolated and sequenced. The initial step in the fractionation was affinity column
      isolation of the peptide-class I complex from either RDM-4 or x5563 tumor cell
      lines. Acid denaturation of the complex followed by HPLC fractionation of the
      peptides allowed us to sequence individual peptides, as well as pools of
      peptides. To date, a total of 10 sequences have been characterized, and all were
      8 mers. The sequences were variable except for glutamic acid in the second
      position (P2) and isoleucine in the eighth (P8), which were highly conserved. To
      further study peptide binding to H-2Kk, a competitive binding assay consisting of
      the immobilized histocompatibility protein and a biotinylated self-peptide for
      signal generation was developed. A complete set of single-alanine variants for
      this one self-peptide was tested in the assay, demonstrating that substitution at
      P2 and P8 markedly decreased the affinity for the class I molecule; alanine at
      position 3 had an intermediate effect on binding. A comparison of the identified
      self-peptides for binding to H-2Kk showed that they differed in affinity by more
      than one order of magnitude. Influenza virus nucleoprotein peptide, SDY EGR LI,
      associated with the plate-bound class I molecule, and the resulting MHC-peptide
      complex could trigger TNF release by influenza-primed CTLs. This result
      demonstrated the functional activity of the plate-bound H-2Kk-peptide complex.

PMID- 7522248
TI  - Trimeric structure of human proliferating cell nuclear antigen. Implications for
      enzymatic function and autoantibody recognition.
AB  - The proliferating cell nuclear Ag (PCNA) is a DNA replication factor postulated
      to function as a sliding clamp around DNA. PCNA is also a target for autoimmunity
      in systemic lupus erythematosus. The autoantigenicity of PCNA is highly
      conformation-dependent, and reaction with most anti-PCNA sera requires a nearly
      full-length PCNA molecule. Here we describe the use of gel filtration and
      glycerol gradient sedimentation to analyze the native structure and size of PCNA.
      PCNA from three sources was studied (PCNA from HeLa cells, PCNA purified after
      its overexpression in bacteria, and PCNA produced in the wheat germ cell-free
      translation system) as well as mutant forms of PCNA translated in vitro. In each
      case, full-length PCNA behaved as a trimer. Analysis of mutant proteins revealed
      a correlation between the trimeric form and binding to the common type of human
      anti-PCNA autoantibody, suggesting that the Abs are specific for the active form
      of the protein. These findings are consistent with the idea that autoantibodies
      are generated as a response to native Ag and provide experimental support for the
      hypothesis that PCNA serves its processive function in DNA replication as a
      trimeric ring structure.

PMID- 7522247
TI  - Subset of CD4+ T cell clones expressing IL-3 receptor alpha-chains uses IL-3 as a
      cofactor in autocrine growth.
AB  - In this paper we demonstrate that IL-3 can act as a cofactor for the growth of
      some CD4+ T cells. This lymphokine synergized with IL-4 to induce both a unique
      set of protein tyrosine phosphorylations and the vigorous proliferation of the
      keyhole limpet hemocyanin-specific and I-Ab-restricted CD4+ Th0 cell clone, E6.
      In addition, neutralizing anti-IL-3 Abs specifically inhibited the growth of E6 T
      cells to Ag or anti-CD3 mAb stimulation. Finally, this T cell clone was shown to
      express both the IL-3R alpha-chain and an IL-3R beta-chain (AlC2A). An
      examination of other CD4+ T cell clones determined that one Th1 clone (A.E7), two
      Th0 clones (16B.2 and L9A.1), and one Th2 clone (D10.G4.1) were not influenced by
      the addition of rIL-3. However, proliferation of the Th2 clones CDC25 and CDC35
      to CD3-stimulation was significantly enhanced by IL-3. The sensitivity of these
      latter two clones to IL-3 was also found to be associated with expression of IL
      3R alpha-chains. Because E6 T cells are highly dependent on IL-4 for autocrine
      growth similar to Th2 cells, these results suggest that IL-3 may synergize with
      IL-4 to enhance the proliferation of a subset of IL-4-dependent CD4+ T cells, and
      the study indicates that IL-3R alpha-chain expression may be a specific marker of
      this CD4+ T cell subset.

PMID- 7522250
TI  - Identification of immunodominant epitopes in Trypanosoma cruzi trypomastigote
      surface antigen-1 protein that mask protective epitopes.
AB  - The gene that encodes trypomastigote surface Ag-1 (TSA-1), a major surface Ag of
      the bloodstream trypomastigote stage of Trypanosoma cruzi, was expressed in a
      baculovirus expression system. To determine the epitope(s) in TSA-1 that was
      recognized during T. cruzi infection and after immunization with TSA-1,
      subregions of the TSA-1 gene were expressed in a bacterial expression system. As
      seen by Western blotting, both mice and rabbits immunized with recombinant TSA-1
      protein, as well as T. cruzi-infected mice, developed strong immune responses to
      the carboxyl-proximal region of TSA-1, but show no reaction to the amino-proximal
      portion of TSA-1. When mice were immunized with either recombinant TSA-1 protein
      or the carboxyl-proximal region of TSA-1, they did not survive challenge with
      10(3) bloodstream trypomastigotes. However, 70% of the mice immunized with the
      amino-proximal portion of TSA-1 survived challenge with 10(3) bloodstream
      trypomastigotes. Thus, the immune responses elicited by recombinant TSA-1 or the
      carboxyl-proximal portion of TSA-1 are nonprotective during T. cruzi infection.
      In contrast, vaccination with the amino proximal region of TSA-1 elicits a
      protective immune response. These results suggest that responses to
      immunodominant epitope(s) within the carboxyl-proximal portion of TSA-1 mask
      epitopes within the amino-proximal portion that are capable of stimulating host
      protective immune responses. It is suggested that immunodominant regions in
      surface molecules such as TSA-1 may provide a mechanism for the parasite to evade
      the host immune response by directing the response away from epitopes that have
      the potential to elicit a reaction that is damaging to the parasite.

PMID- 7522252
TI  - Quantitation of L-selectin and CD18 expression on rabbit neutrophils during CD18
      independent and CD18-dependent emigration in the lung.
AB  - In the systemic circulation, the leukocyte adhesion molecule, L-selectin
      facilitates the initial adhesion of the neutrophil to the inflamed endothelium,
      whereas CD11/CD18 is essential to transendothelial migration. Previous work from
      our laboratory showed that neutrophil emigration in the lung occurs through
      either a CD18-independent or CD18-dependent mechanism, depending on the
      inflammatory stimulus. This study quantitated and compared the surface expression
      of L-selectin and CD18 on neutrophils in the lungs of rabbits during emigration
      toward Streptococcus pneumoniae (a CD18-independent stimulus) and Escherichia
      coli endotoxin (a CD18-dependent stimulus). Ultrathin frozen lung tissue sections
      were immunogold labeled for 1-selectin and CD18, and gold particles were
      quantitated on intravascular, interstitial, and airspace neutrophils by
      transmission electron microscopy. The results show that CD18-independent
      neutrophil emigration was associated with L-selectin down-modulation (78%) and
      CD18 up-modulation (260%) on intravascular neutrophils, before emigration. A
      similar alteration in the expression of L-selectin and CD18 was observed during
      CD18-dependent neutrophil emigration, but only on neutrophils that emigrated into
      the interstitium and airspace. In emigration induced by either stimulus,
      alterations in L-selectin and CD18 expression were restricted to the inflammatory
      focus and emigrated airspace neutrophils consistently expressed greater levels of
      CD18 than intravascular and interstitial neutrophils. We conclude that before
      emigration, L-selectin and CD18 expression on intravascular neutrophils is
      altered only during CD18-independent emigration and only on those neutrophils
      within the inflammatory focus. The increased CD18 expression on airspace
      neutrophils may facilitate bacterial phagocytosis.

PMID- 7522251
TI  - Monocyte chemotactic protein-2, monocyte chemotactic protein-3, and fibroblast
      induced cytokine. Three new chemokines induce chemotaxis and activation of
      basophils.
AB  - Cytokine-dependent mediator release from basophils and mast cells may play an
      important role in the pathogenesis of allergic and inflammatory conditions. Many
      C-C chemokines have been found to activate basophils and mast cells. We
      investigated the effect of three newly identified C-C chemokines, monocyte
      chemotactic protein-2 and -3 (MCP-2, MCP-3) and fibroblast-induced cytokine (FIC)
      on basophils and mast cells. We found that all three cytokines induced histamine
      secretion from basophils in a dose-dependent manner. The secretion of histamine
      was a Ca(2+)-dependent process. MCP-3 was the most potent activator of basophils.
      MCP-3 and FIC activated basophils from all study subjects, whereas the histamine
      release by MCP-2 was donor-dependent. The histamine-releasing activity of MCP-2,
      MCP-3, and FIC was compared with that of MCP-1, RANTES, and macrophage
      inflammatory protein-1 alpha using basophils from 10 donors. MCP-1 was the most
      potent among all the C-C chemokines. However, MCP-3 was nearly as potent. MCP-2,
      MCP-3, and FIC induced significant chemotaxis of basophils. None of the cytokines
      activated mouse peritoneal mast cells. The synthesis of mRNA for MCP-3 was
      investigated by reverse-transcription PCR using allergen-stimulated PBMC and
      bronchoalveolar lavage cells. Both MNC and bronchoalveolar lavage cells expressed
      mRNA for MCP-3. The results of this study indicate that MCP-2, MCP-3, and FIC are
      novel histamine-releasing factors.

PMID- 7522254
TI  - Apoptotic neutrophils are phagocytosed by fibroblasts with participation of the
      fibroblast vitronectin receptor and involvement of a mannose/fucose-specific
      lectin.
AB  - The fate of neutrophils (PMNs) at sites of inflammation is important to our
      understanding of many disease processes. Previously, it had been widely assumed
      that extravasated PMNs inevitably disintegrated before their fragments were
      removed by local phagocytes, but we have recently described an alternative
      process whereby senescent PMNs undergo apoptosis (programmed cell death). This
      process leads to macrophage (Mphi) ingestion of the intact cell by a novel
      phagocytic recognition process. In this study, we show that monolayers of
      fibroblasts also can selectively phagocytose apoptotic PMNs and that the
      recognition of apoptotic PMNs by fibroblasts involves two distinct mechanisms:
      one uses the vitronectin receptor, as in Mphi ingestion of PMNs; the other uses a
      mannose/fucose-specific lectin, which plays no part in Mphi phagocytosis of
      apoptotic PMNs. The direct interactions between PMNs and fibroblasts demonstrated
      herein may have implications for our understanding of the relationship between
      inflammation and scarring in many diseases.

PMID- 7522255
TI  - Association of IgA-Fc receptors (Fc alpha R) with Fc epsilon RI gamma 2 subunits
      in U937 cells. Aggregation induces the tyrosine phosphorylation of gamma 2.
AB  - We investigated the possibility that IgA-binding chains of Fc alpha R on
      monocytic cells are physically associated with gamma 2 subunits of Fc epsilon RI
      (Fc epsilon RI gamma 2 or gamma 2). Fc alpha R was precipitated from lysates of
      IFN gamma-treated U937 cells, subclone 10.6, and probed by immunoblotting with Ab
      against human gamma 2. Fc alpha R was precipitated through anti-Fc alpha R mAbs
      A59 or A62, through A62 from lysates that had been exhaustively precleared of
      high affinity IgG-Fc receptors (Fc gamma RI) and of low affinity Fc gamma RII,
      and through anti-Fc alpha R mAb A77 from Fc gamma RI-precleared lysates of
      untreated 10.6 cells. precipitation was also performed through F(ab')2 A77 and
      through the native ligand of the receptor, hlgA. In all cases, Fc alpha R
      precipitates contained co-isolated 22-kDa gamma 2 (unreduced). The Fc alpha R
      alpha-chain/gamma 2 complex did not readily dissociate in 1% Nonidet P-40 as did
      Fc gamma RI alpha-chain/gamma 2, suggesting a novel aspect to the Fc alpha R
      subunit interaction. Specific Fc alpha R aggregation on cells triggered a robust
      respiratory burst and the tyrosine phosphorylation of several proteins. Among
      them was phospho-gamma 2, which migrated as a 24- to 28-kDa gamma 2
      phosphoprotein on gels and was detected as a 28-kDa phosphoprotein by anti
      phosphotyrosine immunoblot. Aggregated Fc alpha Rs that were precipitated from Fc
      alpha R-triggered cells also contained a phosphoprotein of the same mobility and
      immunoreactivity, as did aggregated Fc gamma RI from which the 28-kDa
      phosphoprotein could be more readily eluted and identified (as phospho-gamma 2).
      We concluded that myelocytic Fc alpha Rs are multichain complexes containing
      gamma 2 subunits that are tyrosine phosphorylated upon Fc alpha R aggregation. As
      IgA is the predominant Ig on mucosal surfaces, gamma-subunits may play an
      important role in mucosal immunity involving leukocytic Fc alpha R.

PMID- 7522253
TI  - P-selectin interacts with a beta 2-integrin to enhance phagocytosis.
AB  - P-selectin is an adhesion molecule for myeloid cells that seems to be essential
      for the development of cellular inflammatory responses. We show that adhesion of
      neutrophils to purified and recombinant P-selectin enhances the phagocytosis of
      unopsonized zymosan particles as judged by the number of cells ingesting
      particles (30.2 +/- 5.8 vs 14.5 +/- 4.0, p = 0.002) and the number of particles
      ingested per cell (percentage increase 58.3 +/- 4.4%. p = 0.0002). The enhanced
      phagocytosis was inhibited by Abs to CD18 or CD11b, suggesting that P-selectin
      alters beta 2-integrin function. The enhancement was only seen in the presence of
      cations allowing the integrin to assume a particular extracellular conformation.
      Furthermore, P-selectin, although not altering the total expression of CD18 on
      neutrophils, significantly increased the binding of mAb 24, which detects an
      activation-dependent epitope. Our results support a signaling role for P-selectin
      in influencing beta 2-integrin function.

PMID- 7522256
TI  - Monocyte vesiculation is a possible mechanism for dissemination of membrane
      associated procoagulant activities and adhesion molecules after stimulation by
      lipopolysaccharide.
AB  - Endotoxin-stimulated monocytes can elicit a dual procoagulant response. They
      express tissue factor and expose phosphatidylserine in the outer leaflet of the
      plasma membrane. Tissue factor, a membrane glycoprotein, is the cellular trigger
      of blood coagulation reactions. Phosphatidylserine is an essential anionic
      phospholipid for surface amplification of thrombin generation. In this study the
      distribution of these two procoagulant entities between activated monocytes and
      derived microparticles was assessed after stimulation by LPS. The presence of
      CD14, CD11a, and CD18, and possible associated adhesion potential were examined,
      particularly on microparticles. Tissue factor was evidenced by using a specific
      functional assay and flow cytometry. Phosphatidylserine exposure was monitored
      through its catalytic activity in a thrombin generation assay and by flow
      cytometry with the use of FITC-conjugated annexin V, a protein probe of anionic
      phospholipids. CD14, CD11a, and CD18 were detected by flow cytometry. The
      interaction of microparticle CD11a/CD18 with intracellular adhesion molecule-1
      was demonstrated by using immobilized recombinant intracellular adhesion molecule
      1 fusion protein. The major part of tissue factor and phosphatidylserine
      dependent procoagulant activity was associated with microparticles after LPS
      stimulation. This was confirmed by flow cytometry. The presence of functional
      CD11a/CD18, and CD14 on microparticles testifies to an associated adhesion
      potential. These results show that membrane vesiculation could be responsible for
      dissemination of inducible monocyte procoagulant activities and suggest that
      derived microparticles could also participate in endothelium stimulation. This
      emphasizes the role of monocyte as a central element in the coupling between
      inflammation/infection and thrombosis.

PMID- 7522257
TI  - Regulation of CD14 expression during monocytic differentiation induced with 1
      alpha,25-dihydroxyvitamin D3.
AB  - CD14, a monocyte/macrophage receptor for the complex of LPS and LPS binding
      protein, is a differentiation marker for the monocyte/macrophage lineage. We have
      analyzed the regulation of CD14 expression during 1 alpha,25-dihydroxyvitamin D3
      (VitD3)-induced monocytic differentiation. Using FACS, Northern blotting, and
      nuclear run-on analyses, we demonstrate that the up-regulation of CD14 expression
      during monocytic cell maturation is regulated mainly at the level of gene
      transcription, and that new protein synthesis is required for CD14 induction. We
      have recently cloned the CD14 5' upstream sequence and demonstrated its tissue
      specific promoter activity. Using stable transfection of the monocytoid U937 cell
      line with a series of deletion mutants of the CD14 5' upstream sequence coupled
      to a reporter gene construct, we show that bp -128 to -70 is the critical region
      for the induction of CD14 expression. This region contains two binding sites for
      the Sp1 transcription factor. A 3-bp mutation at the distal Sp1-binding site not
      only eliminates Sp1 interaction, but also abolishes most of the VitD3 induction
      of CD14 expression. Electrophoretic mobility shift analysis does not detect a
      direct interaction of the CD14 distal Sp1-binding site with the vitamin D3
      receptor and its partner, the retinoid X receptor. These data demonstrate that
      VitD3 induces CD14 indirectly through some intermediary factor, and suggest a
      critical role for Sp1 in this process.

PMID- 7522258
TI  - A single TCR antagonist peptide inhibits experimental allergic encephalomyelitis
      mediated by a diverse T cell repertoire.
AB  - Previously, six T cell clones, which are specific for an encephalitogenic
      determinant of myelin proteolipid protein (PLP) peptide residues 139 to 151
      (HSLGKWLGHPDKF), were derived from SJL mice and shown to use diverse TCR genes.
      To design TCR antagonist peptides that could interfere with the activation of
      these clones in vitro and inhibit experimental allergic encephalomyelitis (EAE)
      in vivo, we first determined the TCR and MHC contact residues of the
      encephalitogenic peptide. The analysis indicated that residues 144 (tryptophan)
      and 147 (histidine) were the TCR binding sites and that residues 145 (leucine)
      and 148 (proline) were important for MHC class II (IAs) binding. On the basis of
      this information, a peptide analogue (leucine 144/arginine 147), in which both of
      the major TCR contact residues were substituted, was synthesized. This analogue
      acts as a TCR antagonist for the panel of PLP 139-151-specific T cell clones,
      does not cause EAE by itself, blocks the induction of disease by the native 139
      151 peptide, and prevents clinical disease progression if administered at the
      first signs of disease. Thus, although multiple TCR genes are used by PLP 139-151
      specific clones, a single peptide analogue can interfere with the disease
      process. This approach should be feasible for designing peptide analogues that
      can be tested for therapeutic efficacy in human autoimmune diseases in which the
      pathogenic Ags are known and TCR use is diverse.

PMID- 7522259
TI  - Protective influences on experimental autoimmune encephalomyelitis by MHC class I
      and class II alleles.
AB  - Experimental autoimmune encephalomyelitis (EAE) is influenced by polymorphism of
      the MHC. We have previously found that Lewis rats with certain MHC haplotypes are
      susceptible to disease induced with the myelin basic protein (MBP) peptide 63-88,
      whereas Lewis rats with other MHC haplotypes are resistant. Interestingly, rats
      with the MHC u haplotype develop an immune response to the MBP 63-88, but do not
      get EAE. In this study we have used intra-MHC recombinant rat strains to compare
      the influences of the MHC u with the a haplotype. We discovered the following: 1)
      The class II region of the MHC a haplotype permits EAE and a Th1 type of immune
      response as measured by IFN-gamma production after in vitro challenge of in vivo
      primed T cells with MBP 63-88. 2) The class II region of the u haplotype is
      associated with a disease-protective immune response characterized by production
      of not only IFN-gamma, but also of IL-4 mRNA expression by the MBP 63-88
      activated cells. 3) The class I region upstream of the class II region of the u
      haplotype is associated with a disease-protective effect and the expression of
      mRNA for TGF-beta after MBP 63-88-induced activation. Thus, such a TGF-beta
      response occurs in all strains expressing the class I Au allele. Treatment with
      Abs to CD8+ cells abrogates peptide-induced TGF-beta mRNA expression, and
      aggravates disease in strains with the class I Au allele.

PMID- 7522260
TI  - Prevalence and role of hepatitis C viraemia in haemodialysis patients in Japan.
AB  - A second generation assay for antibody to hepatitis C virus (anti-HCV) was used
      in order to establish the exact prevalence of HCV infection in haemodialysis
      patients. HCV RNA was sought by the polymerase chain reaction in order to
      determine whether haemodialysis patients with anti-HCV had been infected with HCV
      in the past or were presently infected. Of 357 patients, 198 (55.5%) were
      positive for anti-HCV, compared to 113 (31.7%) positive for original antibody to
      c100-3 protein (P < 0.001). HCV RNA was detected in 171 (86.4%) of the 198
      patients with anti-HCV. Liver dysfunction was found in 63 (17.6%) of all
      haemodialysis patients. Of these, 55 (87.3%) had HCV infection, one (1.6%)
      hepatitis B virus infection while, in the remaining seven, the origin was
      unknown. Thus, in almost all anti-HCV-positive patients, HCV viraemia was
      present. We conclude that HCV is an important cause of liver disease in
      haemodialysis patients.

PMID- 7522261
TI  - Hepatitis C virus infection in haemodialysis patients: a clinical and virological
      study.
AB  - A cohort of 66 patients on maintenance haemodialysis was examined for serological
      (anti-HCV) and virological (HCV-RNA) evidence of infection with hepatitis C virus
      (HCV). Nine (13.6%) were anti-HCV positive, all of whom had detectable HCV-RNA in
      their serum. Statistical analysis of various risk factors (including length of
      time on haemodialysis, history of blood transfusion, history of renal
      transplantation and of previous hepatitis B infection) showed that only the
      length of time on haemodialysis was significantly associated with the acquisition
      of HCV infection. Genotypic analysis showed that five patients were infected with
      genotype 1 and a further two were infected with genotype 4. The latter finding is
      of significance because strains of genotype 4 are extremely uncommon in Western
      Europe. These results demonstrate that intra-unit transmission of HCV-infection
      took place in a group of patients on maintenance haemodialysis.

PMID- 7522262
TI  - Inhibition of fungal growth by Pseudomonas aeruginosa and Pseudomonas cepacia
      isolated from patients with cystic fibrosis.
AB  - This study was undertaken because of the infrequency of infections due to Candida
      species in patients with cystic fibrosis despite their extensive treatment with
      broad-spectrum antibiotics. In vitro susceptibility studies revealed significant
      inhibition of 11 strains of fungi known to infect human beings by 10 strains of
      Pseudomonas aeruginosa and nine strains of Pseudomonas cepacia isolated from the
      sputum of patients with cystic fibrosis. The fungi were Candida krusei, Candida
      keyfr, Candida guillermondii, Candida tropicalis, Candida lusitaniae, Candida
      parapsilosis, Candida pseudotropicalis, Candida albicans, Torulopsis glabrata,
      Saccharomyces cerevisiae and Aspergillus fumigatus. Inhibition of fungal growth
      by Escherichia coli (NCTC 10418), Staphylococcus aureus (NCTC 6571) and
      Haemophilus influenzae (NCTC 11931) could not be demonstrated. The continued
      presence in the sputum of patients with cystic fibrosis of strains of P.
      aeruginosa and P. cepacia, which produce antifungal substances, may inhibit
      growth of Candida species and so prevent overt Candida infections. A. fumigatus
      would seem to be the most important fungus causing disease in patients with
      cystic fibrosis. It is therefore interesting to note that this was the most
      resistant of all the fungi tested for inhibition by P. aeruginosa and P. cepacia.

PMID- 7522263
TI  - An improved non-radioisotopic reverse transcriptase assay and its evaluation.
AB  - We developed an improved, highly sensitive non-radioisotopic (non-RI) reverse
      transcriptase (RT) assay (RTA). While the original non-RI method previously
      reported made use of primer immobilization, our improved method was based on a
      primer-template immobilization procedure. We tested the template specificity,
      reproducibility and linearity of the new method in assays of human
      immunodeficiency virus type-1 (HIV-1) RT. The sensitivities of the method
      previously reported, the improved method and the sensitive radioisotopic (RI-)
      RTA were compared in assays of recombinant HIV-1 RT, partially purified HIV-1
      particles, and the culture supernatant derived from HIV-1-infected cells. For
      each of these samples except the culture supernatant the improved method was the
      most sensitive. It appeared that the fetal bovine serum presented in the culture
      medium interfered with the assay reaction. The curve describing inhibition of the
      assay reaction by fetal bovine serum showed that the highest degree of
      sensitivity in the assay was obtained when the culture supernatant sample was
      diluted four times. With this degree of dilution, the sensitivity of the new
      method for assay of culture supernatant sample was still half that of the
      sensitive RI-RTA. Culture supernatants of five peripheral blood mononuclear cell
      samples obtained from HIV-1-seropositive carriers were assayed by both the
      improved method and the sensitive RI-RTA; and with each of the methods, however
      all virus-positive cultures could be detected. The improved non-RI RTA was
      considered especially useful for assay of culture supernatants for purposes of
      virus isolation because of its advantages of excellent sensitivity and lack of
      requirement for radioisotopes.

PMID- 7522264
TI  - [Relation of gestational age, maternal body weight and age or serum alpha
      fetoprotein and human chorionic gonadotropin at second-trimester].
AB  - Serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG)
      were measured in serum samples of 1,964 pregnant Japanese women whose gestational
      age and singleton pregnancy were confirmed by ultrasound examination during the
      first trimester of pregnancy. Statistical analysis of log-linear regression to
      calculate multiples of the median (MoM) was accomplished by the SAS statistical
      method. The levels of the two analytes noticeably decreased as maternal body
      weight increased. However, maternal age did not have a significant effect on
      either of them. The MoM formulae were as follows: MSAFPMoM = AFP/exp(0.861 +
      0.0685 x gestational age(weeks) - 0.00572 x body weight(kg)). MShCGMoM =
      hCG/exp(6.12 - 0.787 x gestational age(weeks) - 0.00613 x body weight(kg)).
      Gestational age and maternal body weight should be considered as regression
      functions for the adjustment of serum levels in risk estimation of fetal
      anomalies and fetal demise in Japan.

PMID- 7522265
TI  - [Transmission routes of hepatitis C virus: analysis of anti-HCV-positive pregnant
      women and their family members].
AB  - OBJECTIVE: Our purpose was to study the intrafamilial transmission of hepatitis C
      virus (HCV) and the mother-to-child transmission rate of HCV in babies born to
      HCV carrier mothers. STUDY DESIGN: Anti-HCV antibody (anti-HCV) was tested for
      2,528 consecutive pregnant women using an EIA first or second generation kit.
      Babies born to anti-HCV-positive mothers and their family members had their anti
      HCV and HCV RNA checked. These babies were prospectively studied every 3 month
      till 1 year and therafter every 6 month. RESULTS: 1.19% of this population were
      positive for HCV. Eighteen of the 32 anti-HCV-positive pregnant women (56.3%) had
      HCV RNA. Six of 26 of their husbands (23.1%), 4 of 21 of their mothers (19.0%)
      and 6 of 11 of their fathers (54.5%) had anti-HCV, which were much higher
      prevalence rates than in the general population (p < 0.001). Two among 30 samples
      of cord blood from babies born to these pregnant women (6.7%) had HCV RNA. Among
      29 children born to 18 HCV RNA-positive pregnant women, 4(13.8%) had HCV RNA, but
      none of 27 children born to 14 HCV RNA-negative pregnant women. CONCLUSION: It is
      suggested that mother-to-child and intrafamilial transmission of HCV exists.
      Mother-to-child transmission, including by the transplacental route, occurs and
      the rate may be from 5 to 15%.

PMID- 7522266
TI  - [Physiological significance of IGF-I and its binding proteins on fetal growth and
      maturation].
AB  - Insulin-like growth factor-I (IGF-I) is one of growth factors that circulates
      bound to specific, high affinity binding proteins (IGFBPs). Physiological
      significance of IGF-I and IGFBPs on fetal growth is investigated in this study.
      In mother, circulating levels of IGF-I are increased during pregnancy in which
      placental hormones take the place of pituitary GH to regulate IGF-I during
      pregnancy and correlates with fetal birth weight. IGFBPs except IGFBP-1 in the
      maternal circulation are markedly reduced compared to those of non pregnant women
      due to increased activity of protease(s) while IGFBP-1 gradually increased
      throughout pregnancy and negatively correlates with fetal weight. IGF-I
      stimulated 3H-AIB uptake and release by cultured trophoblast cells in a dose
      dependent manner. Furthermore, fetal growth and the transfer of 3H-AIB to fetus
      is inhibited when IGF-I is neutralized by polyclonal antibody. These results
      indicate that maternal IGF-I stimulates fetal growth by activating placental
      transport of nutrients to fetus. In contrast, IGFBP-1 inhibits both 125I-IGF-I
      binding to placental membrane and 3H-glycine uptake of trophoblast cells by IGF-I
      in a dose dependent manner. Moreover, fetal growth and the transfer of 3H-AIB to
      fetus are accelerated when IGFBP-1 is neutralized by polyclonal antibody,
      suggesting that maternal IGFBP-1 inhibits fetal growth by inhibiting IGF-I action
      on the placenta. IGF-I and four IGFBPs including IGFBP-1, -2, -3, and -4 are
      localized in cytotrophoblast of term placenta. Similarly IGFBP-1, -2, and -4 are
      detected in medium conditioned by term decidua cells by Western ligand blot in
      which release of IGFBP-1 and -4 are diminished by IGF-I and all three IGFBPs are
      increased by progesterone. Thus, there is a complicated autocrine/paracrine
      regulation between decidua and placenta and IGF-I action on fetal growth is
      presumed to be modified by this local regulation. Fetal levels of IGF-I and IGFBP
      1 are positively and negatively correlate with fetal weight, respectively. The
      isomers of phosphorylated IGFBP-1 in cord sera are separated by anion ion
      exchange chromatography in which one nonphosphorylated and four phosphorylated
      IGFBP-1 are detected. In pared blood samples from mid-term delivery, percentage
      of nonphosphorylated IGFBP-1 is higher in fetal blood compared to those in
      mother. Similarly, percentage of nonphosphorylated IGFBP-1 is elevated in AFD
      infants than is SFD infants from term delivery. Thus, the proportion of
      nonphosphorylated and phosphorylated isomers of IGFBP-1 varies corresponding to
      fetal growth.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7522268
TI  - Phosphorylated neurofilament epitopes in neuronal perikarya in the septum,
      mesencephalon and dorsal root ganglia of mammals and birds.
AB  - We and other researchers have previously described the presence of axon-specific
      phosphorylated neurofilament epitopes in the cell bodies of three neuronal types
      in the rat: bipolar septofimbrial neurons and the large light A-type cells in the
      dorsal root ganglia and the mesencephalic nucleus of the Vth nerve. This
      spontaneous presence of phosphorylated neurofilaments at the level of the
      perikaryon contrasts with the induced appearance of these epitopes in axotomized
      neurons. We have undertaken a study of this phenomenon in rat, mouse, gerbil,
      rabbit, pig and chicken to analyse its species distribution. Phosphorylated
      neurofilament positive perikarya could be detected in the dorsal root ganglia and
      mesencephalic nucleus of the Vth nerve in all analysed species. Although this
      labelling has been shown to be specific for A-type cells in rat, in pig small
      cells were preferentially labelled, whereas the largest cells were mostly
      completely devoid of label. In the septofimbrial nucleus, phosphorylated
      neurofilament positive perikarya were seen in rat, mouse, gerbil and rabbit. In
      the pig, only a phosphatase-insensitive neurofilament antibody labelled these
      neurons. In the chicken, the labelling was completely absent. These observations
      establish the widespread species distribution of perikaryal phosphorylated
      neurofilament epitopes in the dorsal root ganglia and mesencephalic nucleus of
      the Vth nerve. In the septofimbrial nucleus however, this phenomenon seems to be
      restricted to rodents and lagomorphs. We discuss possible explanations for these
      cytoskeletal singularities in dorsal root ganglia, the mesencephalic nucleus of
      the Vth nerve and septofimbrial neurons.

PMID- 7522267
TI  - CSF concentration gradients of monoamine metabolites in patients with
      hydrocephalus.
AB  - Concentration gradients of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5
      HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), were assessed in 762
      successive CSF fractions (2 ml lumbar CSF) from 15 patients with the adult
      hydrocephalus syndrome (AHS) and 11 patients with hydrocephalus of other causes
      (mixed group). A mean volume of 49.6 (SD 11.8) ml CSF was removed in the AHS
      group and 56.4 (10.2) ml in the mixed group. The CSF was collected with a
      specially designed carousel fraction collector and the corresponding CSF dynamics
      were continuously registered by a constant pressure CSF infusion method.
      Pronounced gradients in CSF HVA and CSF 5-HIAA were seen in both patient groups
      in the first 25 ml of CSF removed. The concentration curves levelled off, despite
      the removal of larger amounts of CSF and stabilised at about twice the initial
      concentrations. This phenomenon has not been described before. Concentrations of
      HVA and 5-HIAA in the first CSF fraction correlated strongly with concentrations
      in fractions up to about 40 ml. A positive correlation between the first fraction
      of CSF HVA and CSF 5-HIAA concentrations and CSF outflow conductance was found in
      the AHS group. There was no gradient in MHPG. It is suggested that the
      rostrocaudal gradients in CSF HVA and 5-HIAA may be explained by a downward flow
      of CSF along the spinal cord with absorption of metabolites occurring during
      passage. Mixing of CSF from different CSF compartments, extraventricular
      production sites of CSF, clearance of metabolites to venous blood or
      extracellular fluid, and CSF outflow conductance are probably important
      determinants of the plateau phase in patients with hydrocephalus. It is concluded
      that lumbar CSF does not exclusively reflect the concentrations of HVA, 5-HIAA,
      or MHPG in the ventricles. It should be noted that these results obtained in
      patients with hydrocephalus may not be applicable to other groups of patients or
      normal subjects.

PMID- 7522269
TI  - Synaptic connections of central carotid sinus afferents in the nucleus of the
      tractus solitarius of the rat. II. Connections with substance P-immunoreactive
      neurons.
AB  - A combined transganglionic transport and immunocytochemical technique was used to
      study the synaptic morphology of central carotid sinus afferents and substance P
      immunoreactive neurons in the commissural subnucleus of the nucleus of the
      tractus solitarius in rats. A large population of substance P-immunoreactive
      neurons (88.32%) were seen in close association with central carotid sinus
      afferents by light microscopy. However, many labelled central carotid sinus
      afferents appeared not associated with substance P-immunoreactive neurons in the
      nucleus of the tractus solitarius. Substance P-immunoreactive neurons were
      spindle, pear, or oval-shaped with a short axis ranging from 5 to 11 microns.
      Their long axis was oriented predominantly in a lateral-medial direction along
      the path of the central carotid sinus afferents from the solitary tract to the
      midline. Synaptic contacts between central carotid sinus afferents and substance
      P-structures, including dendritic profiles of different calibers and somas, were
      readily found by electron microscopy. Many central carotid sinus afferents were
      also found in synaptic contact with non-immunoreactive dendrites and somas.
      Appositions between central carotid sinus afferents and unlabelled axon terminals
      were common, but only in a few cases were morphological manifestations of
      synapses revealed. In the latter, the substance P-immunoreactive terminals
      appeared mostly presynaptic but postsynaptic ones were also encountered. Our data
      provide the evidence that some of the substance P-immunoreactive cells in the
      nucleus of the tractus solitarius are 2nd order neurons of the carotid sinus
      afferent pathway. The possibility that some of the substance P-immunoreactive
      neurons in the nucleus of the tractus solitarius may be interneurons and mediate
      carotid sinus afferent inputs to catecholaminergic neurons in the nucleus of the
      tractus solitarius is considered. Our findings also provide an anatomical
      substrate for a possible presynaptic modulatory role of central carotid sinus
      afferents on the inputs from other brain centers to the substance P-neurons in
      the nucleus of the tractus solitarius.

PMID- 7522270
TI  - Patterns of glial development in the human foetal spinal cord during the late
      first and second trimester.
AB  - Although the presence of radial glia, astrocytes, oligodendrocytes and microglia
      has been reported in the human foetal spinal cord by ten gestational weeks,
      neuroanatomic studies employing molecular probes that describe the interrelated
      development of these cells from the late first trimester through the late second
      trimester are few. In this study, immunocytochemical methods using antibodies to
      vimentin and glial fibrillary acidic protein were used to identify radial glial
      and/or astrocytes. An antibody to myelin basic protein was used for
      oligodendrocytes and myelin; and, an antibody to phosphorylated high and medium
      molecular weight neurofilaments identified axons. Lectin histochemistry using
      Ricinus communis agglutinin-I was employed to identify microglia. Vibratome
      sections from 35 human foetal spinal cord ranging in age from 9-20 gestation
      weeks were studied. By 12 gestational weeks, vimentin-positive radial glia were
      present at all three levels of the spinal cord. Their processes were easily
      identified in the dorsal two-thirds of cord sections, and reaction product for
      vimentin was more intense at cervical and thoracic levels than lumbosacral
      sections. By 15 gestational weeks, vimentin-positive processes were radially
      arranged in the white matter. At this time, glial fibrillary acidic protein
      positive astrocytes were more obvious in both the anterior and anterolateral
      funiculi than in the dorsal funiculus, and the same rostral to caudal gradient
      was seen for glial fibrillary acidic protein as it was for vimentin. Myelin basic
      protein expression followed similar temporal and spatial patterns. Ricinus
      communis agglutinin-I labelling revealed more microglia in the white matter than
      in grey matter throughout the spinal cord from 10-20 gestational weeks. By 20
      gestational weeks, the gradients of glial fibrillary acidic protein and vimentin
      expression were more difficult to discern. White matter contained more microglia
      than grey matter. These results suggest that astrocytes as well as
      oligodendrocytes follow anterior-to-posterior and rostral-to-caudal developmental
      patterns in the human foetus during middle trimester development.

PMID- 7522274
TI  - 3rd Congress of the European Association for Palliative Care. Bergen, Norway,
      June 15-19, 1994. Abstracts.

PMID- 7522273
TI  - Those days are long gone now.

PMID- 7522271
TI  - Expression of the extracellular matrix glycoprotein tenascin in the somatosensory
      cortex of the mouse during postnatal development: an immunocytochemical and in
      situ hybridization analysis.
AB  - Layer 4 of the rodent somatosensory cortex contains the barrel field which is the
      cortical representation of the whisker pad located on the contralateral side of
      the face. Each barrel within the barrel field is related one to one to its
      corresponding whisker both anatomically and physiologically. The astrocyte
      derived extracellular matrix glycoprotein tenascin has been shown by
      immunocytochemistry to delineate the boundaries between barrels during their
      formation until the end of the second postnatal week. The present study describes
      the anatomical localization of tenascin mRNA expressing cells in the
      somatosensory cortex of the mouse from birth to postnatal day 15. During this
      time, a general down-regulation of tenascin-specific message was observed as a
      function of the state of maturation, with layers 5 and 6 down-regulating the
      message earlier than layers 1 and 2/3. Tenascin (as detected by
      immunocytochemistry) also revealed this gradual down-regulation with maturation.
      Layer 4 of the somatosensory cortex was different in that, with the onset of
      formation of barrel field boundaries at postnatal day 3, tenascin protein and
      mRNA were down-regulated more in layer 4 than in the upper and the lower layers
      of the somatosensory cortex and, interestingly, not in layer 4 of adjacent
      cortical areas. At postnatal day 6 tenascin immunoreactivity was most clearly
      distinguished in the barrel field boundaries while tenascin-specific mRNA was no
      longer detectable in layer 4. Down-regulation of tenascin message was also seen
      at P6 at the level of the enlarged barrel corresponding to an early postnatal
      lesioned row of whiskers. At postnatal day 15, tenascin protein and mRNA were no
      longer detectable in the somatosensory cortex. Distribution of glial fibrillary
      acidic protein immunoreactivity did not reveal any preferential accumulation of
      GFAP-positive radial glial processes in barrel field hollows versus barrel field
      boundaries at any stage.

PMID- 7522275
TI  - Collagen synthesis inhibitors disrupt embryonic cardiocyte myofibrillogenesis and
      alter the expression of cardiac specific genes in vitro.
AB  - The extra-cellular matrix has been demonstrated to play an important role in the
      differentiation of a number of cell types in vitro. The purpose of this study was
      to establish the role of ECM collagen synthesis in regulating growth and
      differentiation of embryonic cardiocytes in vitro. We report that treatment of
      embryonic cardiocytes in vitro with two chemically distinct inhibitors of
      collagen synthesis, cis-hydroxy-L-proline and ethyl-3,4-dihydroxybenzoate,
      effectively inhibits collagen secretion. This results in disruption of
      myofibrillogenesis as seen by immunocytochemistry and electron microscopy, and
      absence of beating. The expression of muscle specific genes TroponinT and Myosin
      Heavy Chain are reduced, while the expression of the housekeeping gene
      glyceraldehyde phosphate dehydrogenase is uneffected. All of these effects are
      reversible. The structural effects are not prevented by growing the cells on
      various substrates, including denatured collagen, collagen type IV, laminin and
      Matrigel. Thus, inhibition of collagen secretion disrupts myofibrillogenesis and
      results in the alteration of expression of muscle-specific genes, suggesting that
      collagen synthesis plays an essential role in maintaining the differentiated
      phenotype of cardiocytes.

PMID- 7522272
TI  - Epstein-Barr virus in nasal T-cell lymphomas (polymorphic reticulosis/midline
      malignant reticulosis) in western China.
AB  - Polymorphic reticulosis (PR) or midline malignant reticulosis (MMR) is considered
      to be malignant, or at least pre-malignant T-cell proliferations of the nose or
      midline area. Recent reports of small series of nasal T-cell lymphomas have shown
      a strong association with Epstein-Barr virus (EBV). Furthermore, a peculiar
      phenotype is described, with expression of CD56 and not of CD3, suggesting a
      possible origin from natural killer (NK) cells. We have analysed a series of 38
      cases of PR/MMR for the presence of EBV by in situ hybridization (ISH) of the EBV
      encoded RNAs 1 and 2 (EBER). Twenty cases were tested for expression of EBV
      encoded latent membrane protein 1 (LMP-1). Special attention was also paid to the
      expression of CD3 and the NK cell-related marker CD56. Thirty-two cases (84 per
      cent) showed positive EBER ISH. In 5 of 20 cases, LMP-1 expression was detected.
      In three cases, a few scattered cells were positive, and in two cases, LMP-1 was
      detected in clusters of atypical cells. Most of the neoplasms showed expression
      of CD3 (89 per cent) and in 27 cases (71 per cent), CD56 was detected. These
      results are consistent with an aetiopathogenetic role for EBV in most, but not
      all, cases of PR/MMR. Our findings are less supportive of a major role for LMP-1
      in tumour genesis. CD3 expression in most of the cases of PR/MMR underlines the T
      cell origin of these neoplasms, often with aberrant expression of CD56.

PMID- 7522276
TI  - An excitatory muscarinic response in neonatal rat ventricular myocytes and its
      modulation by sympathetic innervation.
AB  - Previously, we demonstrated that low concentrations of acetylcholine (< or = 10(
      9) M) increased automaticity in neonatal but not in adult rat ventricular
      myocardium. In the present study, we used cultured neonatal rat ventricular
      myocytes grown alone or in the presence of dissociated sympathetic neurons as an
      experimental model to study the ontogeny of the muscarinic response. McN A343 (<
      or = 10(-9) M), an M1 selective agonist, increased spontaneous rate from 51 +/- 4
      to 56 +/- 5 beats per minute (bpm), and this excitatory response was blocked by
      10(-9) M pirenzepine, an M1 selective antagonist, but not by the M2 selective
      antagonist AFDX-116, nor by the alpha 1 adrenergic antagonist prazosin and the
      beta adrenergic antagonist propranolol (all 10(-7) M) In innervated myocytes, McN
      A343 also increased rate from 48 +/- 6 to 55 +/- 6 bpm. However, this effect was
      blocked by either 10(-9) M pirenzepine or 10(-7) M propranolol. After
      pretreatment with 10 ng/ml of pertussis toxin, the McN A343-induced excitatory
      response in non-innervated myocytes was absent, thus suggesting that this
      response involved a pertussis toxin-sensitive G protein dependent pathway. McN
      A343 failed to stimulate inositol phosphate or cAMP accumulation in non
      innervated myocytes. These results demonstrate the following. (1) The muscarinic
      excitatory response is mediated via direct stimulation of a post-synaptic M1
      receptor in non-innervated myocytes. (2) The excitatory response after
      innervation is related to the release of catecholamines, possibly through
      activation of muscarinic receptors located at the pre-synaptic sympathetic nerve
      terminals. (3) Sympathetic innervation prevents the functional expression of the
      post-synaptic myocardial M1 receptor. (4) The intracellular pathway for the post
      synaptic M1 excitatory response involves a pertussis toxin-sensitive G protein,
      but does not depend on obvious changes in cAMP or phosphoinositide hydrolysis.

PMID- 7522277
TI  - [Development and predictive factors of hepatocellular carcinoma in patients with
      chronic liver disease over a long follow-up period].
AB  - We performed periodical examinations by ultrasonography (US) and serum alpha
      fetoprotein in 272 patients with liver cirrhosis (male, 167; female, 105) over
      long follow-up periods (1985. 1-1992.9). The average period was 1934 days, and we
      prospectively studied the early detection of hepatocellular carcinoma (HCC). HCC
      was detected in 78 patients during the periods, with the average cumulative
      incidence rate being per year 7%. Tumor size at detection was 15mm or less in
      diameter in 37.2% HCC patients and 30mm or less in 89.7%. In spite of frequent
      ultrasonic examinations, it was difficult to detect small sized HCCs in blind
      spots of US or in the liver with the rough parenchymal echo pattern. Predictive
      factors important for development of HCC were analyzed using Cox's proportional
      hazards model. It showed that significant factors were serum AFP level, liver
      parenchymal echo pattern and small mass lesions (ultrasonic appearance) of the
      liver.

PMID- 7522279
TI  - [Proliferation of pulmonary fibroblasts obtained from rats with bleomycin-induced
      pulmonary fibrosis and effects of rat rIL-1 alpha on this proliferation].
AB  - To clarify the mechanism of pulmonary fibrosis, the growth rate of fibroblasts
      obtained from bleomycin (BLM)-treated rats was compared with that of fibroblasts
      obtained from control rats. Proliferation of fibroblasts obtained from rats at 4
      days after BLM instillation (BRF) was significantly more rapid than that of
      fibroblasts obtained from rats at 4 days after saline instillation (CRF), as
      assessed by cell counting and 3H-TdR incorporation. CRF and BRF were separated by
      the method of discontinuous Percoll gradients. Three fibroblast fractions of
      specific gravity (S.G.), S.G. < 1.036, 1.036 < or = S.G. < 1.050, 1.050 < or =
      S.G. < 1.062, were obtained. Percentages of the densest fibroblast fraction were
      46.2 +/- 5.2 in BRF and 6.4 +/- 2.8 in CRF. The densest fibroblasts in BRF
      proliferated more rapidly than the least dense fibroblasts. Rat rIL-1 alpha
      suppressed the proliferation of CRF and BRF, dose dependently. These results
      suggest that an increase in the densest fibroblasts in the lung might correlate
      with BLM-induced pulmonary fibrosis and that IL-1 alpha suppresses the
      proliferation of pulmonary fibroblasts.

PMID- 7522278
TI  - [The diagnosis of hepatocellular carcinoma determined by pattern of AFP bands
      separated by Con A affinity electrophoresis].
AB  - We analyzed the Con A affinity of serum AFP in patients with a serum AFP
      concentration greater than 50ng/ml by antibody affinity electrophoresis and
      Western blotting to distinguish hepatocellular carcinoma (HCC) from benign
      chronic liver diseases (CLD). Of 164 patients with HCC, 48 (29.3%) had a single
      band, while 116 (70.7%) had multiple bands. All but three of 65 patients with
      cirrhosis had a single band. All but one of 32 patients with chronic hepatitis
      had a single band. We concluded that multiple AFP bands are diagnosis of HCC.
      This method is a useful assay for distinguishing HCC from CLD.

PMID- 7522281
TI  - Partial compliance: implications for clinical practice.
AB  - Modern therapeutics unavoidably requires integration of a patient's medication
      taking behavior in assessing the clinical response to treatment. Automatic
      escalation of the drug regimen whenever the treatment goal is not achieved
      carries major risks and should be discouraged. Medication-taking behavior, when
      studied carefully by dynamic measures like electronic monitors, displays marked
      inter- and intra-subject variability over time. Most deviations from the
      prescription are underdosings and occur randomly, rather than consistently or
      systematically. Such deviations are frequent, difficult to detect by traditional
      measures, and hard to predict from common baseline characteristics. Compliance
      tends to fall as dosing frequency rises above once daily. Better measures of
      medication-taking behavior permit evaluation of both adverse drug reactions and
      secondary resistance to therapy as resulting from pill taking itself. Negative
      consequences of partial compliance among hypertensive patients include marked
      increases in rates of rehospitalization and rates of coronary events. One
      alternative strategy to labor-intensive interventions for improving compliance is
      to develop longer-acting medications, which compensate in part for lapses in
      dosing frequency. Such a strategy reflects a search for therapeutic sufficiency
      rather than a rigid concordance between the prescription and medication-taking
      behavior.

PMID- 7522280
TI  - [Surgical methods in the treatment of colonic obstruction].
AB  - The treatment of 365 patients with carcinoma of the colon complicated by
      intestinal obstruction is analysed. In 30.9% of patients the signs of acute
      obstruction were relieved by decompression therapy including a method suggested
      by the authors. The other patients were subjected to an urgent and even emergency
      operation. Two group of patients are compared. I the first group the traditional
      surgical tactics were used, in the second group new methods for decompression of
      the large intestine were applied both before and during the operation:
      endolymphatic and intravenous infusion of antibiotics, formation of double
      channel colostomy of the type of "partial anastomosis". With such changed tactics
      the number of postoperative complications and fatal outcomes reduced from 38.7
      and 20.4% to 12.1 and 6.4%, respectively. The percentage of patients subjected to
      a radical operation increased from 69.3 to 85.7%.

PMID- 7522282
TI  - A double-blind, long-term, comparative study on quality of life, safety, and
      efficacy during treatment with amlodipine or enalapril in mild or moderate
      hypertensive patients: a multicenter study.
AB  - Amlodipine (5-10 mg, once daily) and enalapril (10-40 mg, once daily) were
      compared in terms of quality of life, efficacy, and tolerability, in a
      multicenter, double-blind trial lasting for 50 weeks in 461 mild or moderate
      hypertensive patients. Both drugs were similarly effective in lowering blood
      pressure while maintaining quality of life. Apart from class-typical effects,
      such as edema for calcium antagonists, and cough for angiotensin-converting
      enzyme inhibitors, both drugs were equally well tolerated, with few adverse
      effects of clinical significance. Only a few patients [eight amlodipine (4%);
      nine enalapril (4%)] were withdrawn from the trial due to drug-related adverse
      events, demonstrating that tolerability was good. Neutral to slightly beneficial
      effects were found in blood lipid concentrations after treatment with amlodipine.
      Both drugs reduced the calculated risk of coronary heart disease over the next 10
      years. It was concluded that amlodipine compared favorably with enalapril as an
      effective and well-tolerated antihypertensive drug.

PMID- 7522283
TI  - Comparison of amlodipine and captopril in hypertension based on 24-hour
      ambulatory monitoring.
AB  - The efficacy and toleration of once-daily amlodipine (5-10 mg o.d.) and captopril
      (25-50 mg b.i.d.) were compared in 45 patients with mild-to-moderate essential
      hypertension. Twenty-four-hour ambulatory blood pressure monitoring was performed
      at baseline and at the end of the 8-week study period. Clinic blood pressure,
      heart rate, and adverse events were assessed during a placebo run-in and after 2,
      4, and 8 weeks of treatment. Both amlodipine and captopril significantly reduced
      clinic blood pressure without affecting heart rate. Between-treatment comparisons
      showed that amlodipine produced a significantly greater reduction in sitting
      diastolic blood pressure than captopril. Ambulatory blood pressure monitoring
      revealed a sustained reduction in both systolic and diastolic blood pressure
      throughout a full 24-h period in patients taking amlodipine. In contrast,
      however, the effects of captopril were no longer evident during the final 3 h of
      the dosing interval. Both drugs were generally well tolerated, and the incidence
      of adverse events was similar in each group. This study demonstrates that
      amlodipine is more effective as a once-daily antihypertensive agent than
      captopril administered twice daily.

PMID- 7522284
TI  - Long-term efficacy of amlodipine in patients with severe coronary artery disease.
AB  - The long-term efficacy of amlodipine was assessed in 21 patients with chronic
      stable angina. After a 2-week run-in period, patients received 5 mg amlodipine
      once daily for 2 weeks. This was increased to 10 mg daily during the following 10
      week dose-adjustment/maintenance phase, if angina attacks were not abolished.
      Patients were then followed up for an additional 21 months (total 24 months).
      During follow-up, patients were evaluated at least once a month, and sitting
      blood pressure and heart rate were monitored. Angina attack rate and
      nitroglycerin consumption were recorded in angina diaries throughout the study.
      Patients underwent a treadmill exercise test at baseline, at the end of the dose
      adjustment phase and again during long-term follow-up at 20 months. Amlodipine
      (mean final daily dose, 8.2 mg) resulted in a significant reduction in angina
      attack rate and nitroglycerin consumption (both p < 0.001), which was maintained
      during follow-up. Systolic blood pressure was also reduced (p < 0.01) by
      amlodipine. Diastolic blood pressure and heart rate were not significantly
      affected. Amlodipine significantly increased mean exercise time (p < 0.001). ST
      segment depression at maximum common load was reduced when compared with baseline
      values (p < 0.001), and the metabolic equivalent (MET) score at peak exercise was
      significantly improved by amlodipine (p < 0.001). All of these effects on
      exercise performance were sustained during follow-up. These data indicate that
      long-term treatment with amlodipine, in patients with severe coronary artery
      disease, reduced the number of angina attacks and nitroglycerin consumption and
      produced a sustained improvement in exercise performance.

PMID- 7522285
TI  - Evaluation of the acute hemodynamic and electrophysiologic effects of intravenous
      amlodipine alone and in combination with a beta-blocker in patients with angina
      pectoris.
AB  - The acute hemodynamic and electrophysiologic effects of intravenous amlodipine (2
      x 10 mg), administered either alone or on a background of beta-blocker therapy,
      were studied in 25 patients with angina pectoris. Hemodynamic assessments showed
      that amlodipine produced significant decreases in systemic vascular resistance
      and systemic blood pressure, and increases in stroke volume and cardiac output in
      both treatment groups. Electrophysiologic evaluation revealed that neither sinus
      node function, nor HIS ventricular conduction, were altered with amlodipine.
      Therefore, acute intravenous administration of amlodipine alone or in combination
      with a beta-blocker does not appear to compromise left ventricular performance,
      sinus node function, or intracardiac conduction.

PMID- 7522286
TI  - Amlodipine; clinical relevance of a unique pharmacokinetic profile.
AB  - Although it has long been recognized that many antihypertensive drugs exhibit
      large intersubject variability in their disposition characteristics, the concept
      that this translates into a high variability in response has largely been
      ignored. Thus, too often in the past, research into antihypertensive drugs has
      ignored the importance of underlying plasma drug concentrations and has sought to
      attribute the variability in antihypertensive response to factors such as age and
      plasma renin activity. In studies with hypertensive patients in which
      pharmacokinetic and pharmacodynamic indices have been integrated, we have
      demonstrated that the intersubject variability in the pharmacokinetics of
      verapamil, nifedipine, enalapril, and amlodipine is directly related to the
      variability in blood pressure response at steady state. The characteristic low
      variability in the peak and predose, steady-state plasma concentrations
      associated with amlodipine are reflected in a correspondingly low variability in
      the blood pressure response. In addition, using the trough-to-peak, steady-state,
      blood pressure response as an index of 24-h duration of action, amlodipine
      exhibited significantly higher values with lower variability (66 +/- 11%) when
      compared to verapamil (47 +/- 13%), nifedipine (48 +/- 9%) and enalapril (44 +/-
      15%). Concentration-effect analyses of all four drugs revealed that the
      antihypertensive response could be related to circulating drug concentrations and
      that the response following administration of the first dose correlated well with
      the response following long-term treatment.

PMID- 7522287
TI  - Side effects of dihydropyridine therapy: comparison of amlodipine and nifedipine
      retard.
AB  - The efficacy and tolerability of amlodipine (5 mg, once daily), nifedipine retard
      (20 mg, twice daily), and placebo were compared in a multicenter, three-way,
      crossover study involving 97 patients with mild-to-moderate hypertension. Each
      patient underwent three, 2-week treatment periods separated by 2-week washout
      periods without therapy. Comparable and significant (p < 0.05) blood pressure
      reductions were observed after amlodipine and nifedipine retard when compared
      with placebo, except in the case of supine systolic blood pressure with
      nifedipine retard. A significantly greater incidence of treatment-related side
      effects was observed with nifedipine retard (41%) compared with amlodipine (27%,
      p < 0.05) or placebo (16%, p < 0.01). Amlodipine treatment was associated with
      significantly fewer reports of headache and flushing than nifedipine retard (p <
      0.05). The lower incidence and reduced severity of vasodilator side effects
      associated with amlodipine resulted in fewer withdrawals and a better overall
      tolerability profile.

PMID- 7522288
TI  - Cancer combination chemotherapy with retinoids: experimental rationale.
AB  - Retinoids, cytokines as well as 1,25-dihydroxyvitamin D3 and its analogs are all
      classes of compounds with pleiotropic actions. They inhibit proliferation in
      human transformed epithelial cell lines and induce differentiation in human
      transformed hemopoietic cell lines. In a murine model of tumor cell-induced
      angiogenesis all three classes of compounds inhibit the formation of new blood
      vessels, necessary for supplying the growing tumor with oxygen and nutrients.
      Combinations of compounds from the three different classes lead to higher
      efficacy than the compounds administered as single agents. The effects of
      combinations vary depending on the individual representatives of the three
      classes and on the particular test models used. Additive, synergistic and
      potentiating effects have been observed. The results obtained in experimental
      systems raise hope that combination therapy might be useful in the treatment of
      certain human neoplastic diseases.

PMID- 7522289
TI  - Hematopoietic growth factor stimulation and cytarabine cytotoxicity in vitro:
      effects in untreated and relapsed or primary refractory acute myeloid leukemia
      cells.
AB  - Stimulation of clonogenic acute myeloid leukemia (AML) cells by hematopoietic
      growth factors (HGF) is capable of enhancing cytosine-arabinoside (Ara-C)
      cytotoxicity in vitro. Until now it has not been known to what extent in vitro
      Ara-C cytotoxicity can be restored by HGF stimulation in samples from previously
      treated AML patients. Therefore, we studied the individual effects of the
      hematopoietic growth factors (HGF) granulocyte colony-stimulating factor (G-CSF),
      interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM
      CSF) stimulation on the Ara-C sensitivity of clonogenic leukemic cells from six
      patients with newly diagnosed AML. These results were directly compared with the
      outcome using AML samples from the same patients at relapse or primary refractory
      AML. In one patient, a sample of the second relapse was also studied. The results
      were expressed as IC50 values, and were used to calculate sensitivity ratios,
      defined as the ratio of the IC50 value with drug exposure alone and with HGF plus
      Ara-C. In AML samples treated with Ara-C alone and no HGF, IC50 values of Ara-C
      in relapsed/refractory AML were greater than IC50 values of AML cells at
      diagnosis. Addition of either HGF enhanced the Ara-C cytotoxicity for the
      relapsed samples significantly (for G-CSF p = 0.036, IL-3 p = 0.036, and for GM
      CSF p = 0.036). The values of Ara-C sensitization of AML samples due to HGF at
      relapse did not significantly differ from those at diagnosis. However,
      enhancement of Ara-C cytotoxicity to AML progenitors by IL-3 or GM-CSF
      stimulation was significantly less in the cell specimens from AML recurrence
      patients as compared with the original diagnosis samples. In three AML samples at
      diagnosis and at their relapse, Ara-C incorporation into the DNA was determined.
      IL-3 stimulation enhanced Ara-C incorporation in all samples tested.
      Nevertheless, Ara-C incorporation in the relapsed samples was significantly less
      than that in the diagnosis samples of the same patients. A good correlation
      between Ara-C incorporation and bromodeoxyuridine (BrdU) incorporation was found.
      The results indicate that HGF stimulation in relapsed/refractory AML enhances Ara
      C cytotoxicity, but not to the level that was observed with AML samples at
      diagnosis.

PMID- 7522291
TI  - Correlation between cell morphology and expression of the AML1/ETO chimeric
      transcript in patients with acute myeloid leukemia without the t(8;21).
AB  - The 8;21 chromosomal translocation involves the AML1 gene on chromosome 21 and
      the ETO gene on chromosome 8 and results in the transcription of a chimeric
      message. This translocation is most often associated with acute myelogenous
      leukemia with maturation (AML-M2). The leukemic cells of patients carrying
      t(8;21) often exhibit several characteristic morphologic features. We identified
      four cases in which the morphology led us to suspect a t(8;21), but in which this
      translocation was not observed by cytogenetic analysis. In two of the four cases,
      an AML1/ETO chimeric fragment was detected by reverse transcription and
      polymerase chain reaction (RT-PCR), and its sequence was found to be identical to
      that from patients with a cytogenetically proved t(8;21). Marrow specimens of the
      four patients lacking the t(8;21) cytogenetically were reviewed retrospectively
      with regard to seven morphologic features commonly reported to be associated with
      this translocation, and the results were compared to 13 morphologic controls with
      the t(8;21). Although none of the 13 controls had all of the characteristic
      morphologic features, all had at least six, as did the two t(8;21)-negative but
      RT-PCR-positive patients. The two patients who lacked the t(8;21) and who were RT
      PCR-negative showed only three and four of these morphologic features,
      respectively. Both of the RT-PCR-positive patients had deletions of the long arm
      of chromosome 9, a common change associated with a t(8;21), supporting our
      assessment of these patients as having a cytogenetically undetected t(8;21).

PMID- 7522293
TI  - IL-4 inhibits the LPS-induced expression of CD14 and monocyte-specific esterase
      mRNA in MONO-MAC-6 cells.
AB  - The human MONO-MAC-6 cell line expresses the monocyte-associated differentiation
      markers CD14 and monocyte-specific esterase (MSE) and can be stimulated by
      lipopolysaccharide (LPS) to produce high mRNA levels of monocyte-related
      cytokines. This similarity to human peripheral blood monocytes (PBMo) renders
      this cell line a promising model for studies of monocyte activation and
      differentiation. Interleukin-4 (IL-4) is known to act antagonistically to LPS
      during the activation process of PBMo, inhibiting the production of cytokines.
      Therefore, this study was designed to compare the effects of IL-4 and LPS on the
      expression of monocytic markers and tumor necrosis factor alpha (TNF alpha) mRNA
      on PBMo and the MONO-MAC-6 cell line. IL-4 inhibited the LPS-induced expression
      of TNF alpha mRNA in PBMo and downregulated the LPS receptor CD14 but it had no
      influence on MONO-MAC-6 cells regarding these parameters. However, upregulation
      of CD14 and MSE mRNA expression in the cell line by a 2-day incubation with LPS
      were inhibited by IL-4. This response to IL-4 after long-term treatment with LPS
      was seemingly contradictory to the missing reduction of TNF alpha mRNA expression
      after short-term incubation with LPS. Obviously long-term treatment with LPS made
      the cells responsive to IL-4. The increase in responsiveness was not due to IL-4
      receptor (IL-4R) upregulation, as LPS did not influence the constitutive
      expression of the IL-4R.

PMID- 7522292
TI  - Expression of beta 1 integrin mRNAs in human leukemic blasts.
AB  - Adhesion receptors from the very late activation (VLA) (beta 1) integrin
      subfamily play a role in the cooperation of hematopoietic progenitors with bone
      marrow stroma, and the disregulated expression of these molecules, as evaluated
      by immunophenotyping, has been implicated in the acquisition of the malignant
      phenotype by hematopoietic cells. In the present study, Northern hybridization
      was used to determine the pattern of expression of transcripts for VLA subunits
      in: (i) leukemic blasts obtained from the peripheral blood of ten patients with
      acute myelogenous leukemia (AML) of different FAB subclasses; (ii) the human
      leukemic cell lines KG-1, HL-60, K-562, HEL and U-937; and (iii) normal
      hematopoietic cells. Most of the AML blasts and the cultured leukemic cells
      expressed mRNAs for the beta 1 and alpha 5 subunits (the only exception among the
      cell lines was KG-1 cells) and these transcripts were also found in normal bone
      marrow progenitors, peripheral blood mononuclear cells (PBMNC), and peripheral
      blood monocytes. While the alpha 4 transcript was detected in all cultured cells
      but K-562, and in normal circulating monocytes, it occurred in blasts from only
      two AML patients and was weakly expressed in mature PBMNC. No specific pattern of
      expression of beta 1, alpha 5, and alpha 4 transcripts could be related to cell
      differentiation or maturation in the AML blasts and leukemic cell lines tested.
      None of the primary AML blasts or cultured cells showed mRNA messages for alpha
      2, alpha 3 or alpha 6 chains of the beta 1 integrins. The results suggest that,
      in some cases of AML, the malignant phenotype of leukemic blasts may be
      associated with down-regulated transcription of the alpha 4 integrin subunit.

PMID- 7522290
TI  - Analysis of mutations in the GM-CSF receptor alpha coding sequence in patients
      with acute myeloid leukaemia and haematologically normal individuals by RT-PCR
      SSCP.
AB  - Mutations of signal transducing molecules such as Ras have been shown to confer a
      growth advantage in leukaemic blasts and contribute to the pathogenesis of the
      disease. Alterations of signal transducing molecules other than Ras may play a
      role in leukaemogenesis. Knowledge of such mutations could also further our
      understanding of the normal signalling processes. We have therefore studied the
      coding sequence of the GM-CSF receptor alpha chain (GM-CSFR alpha) in patients
      with acute myeloid leukaemia (AML) and non-AML controls using single strand
      conformation polymorphism (SSCP) analysis. Abnormalities were detected in 4/32
      AML patients (13%) and 2/15 non-AML controls (13%). Direct sequencing of PCR
      products revealed five different base substitutions. Three were conservative, two
      caused amino acid changes. The base substitution leading to amino acid change
      alanine to glycine at position 17 was found in both an AML patient and a control.
      It lies in the signal sequence and does not affect the mature protein. The other
      base change altering arginine to glutamine at position 164 is unlikely to
      influence the receptor structure as this structural position in the chain is not
      well conserved in members of the cytokine receptor family. Both amino acid
      changes were constitutive alterations as they could be demonstrated in the
      patients' children. The base changes described in the AML patients thus represent
      polymorphisms and do not contribute to the pathogenesis of AML.

PMID- 7522294
TI  - Leukemia-associated changes identified by quantitative flow cytometry. II. CD5
      over-expression and monitoring in B-CLL.
AB  - The CD5 antigen density on B cells was studied on fetal spleen, cord blood, and
      adult peripheral blood (after immunomagnetic bead purification) using an indirect
      immunofluorescence technique. In fetal spleen, there was a continuum in CD5
      expression, whereas all cord blood and less than 20% adult peripheral blood B
      cells were CD5+. Mean CD5 antigen density on these normal cells was low (3-6 x
      10(3) molecules/cell); eight to 20 times lower than on normal T lymphocytes. In
      adult blood, less than 10% B cells expressed more than 3 x 10(3) CD5
      molecules/cell. In chronic malignancies, 34/35 cases had a CD5 antigen density
      lower than on residual T cells, but mean antigen density was higher (14.8 +/- 2.1
      x 10(3) molecules/cell) than on normal B cells. Sixteen cases of chronic
      lymphocytic leukemia (50%) expressed a CD5 density above 10 x 10(3)
      molecules/cell. This aberrantly high CD5 expression was used to detect neoplastic
      cells after dilution in normal lymphocytes, with a limit of detection between
      1:100 and 1:1000. Quantitation of the CD5 antigen allows better characterization
      of the B1 population and should be used for the monitoring of chronic
      malignancies.

PMID- 7522296
TI  - Recent progress in chronic lymphocytic leukemia. International Workshop on
      chronic Lymphocytic Leukemia.
AB  - The data we discuss indicate substantial recent progress in understanding and
      treating CLL. However, despite considerable new information, many of the
      intriguing issues we posed at previous IWCLL meetings remain unanswered.
      Prominent among these are the questions of what causes CLL, what is the relation
      between CLL and normal B-cell development, are T-cell abnormalities a cause of
      consequence of CLL, why are auto-immune features so prominent and how is CLL best
      treated? Although these gaps in our knowledge are unfortunate, they give us the
      opportunity for yet another IWCLL meeting: 1996 in Greece. More to follow.

PMID- 7522295
TI  - Flow cytometric detection of residual disease in acute leukemia by assaying
      blasts co-expressing myeloid and lymphatic antigens.
AB  - A method employing CD45-gating of blast cells was evaluated for the flow
      cytometric detection of residual disease in CD19- and myeloid antigen-positive
      acute leukemia in morphologic remission. In the normal bone marrow, CD45-gating
      identified at least three populations of immature cells, one of which appeared to
      retain a minute fraction of CD19- and CD13/33-antigen co-expressing cells. In
      acute leukemia, CD45 expression separated the blast cell population from the
      normal marrow cell populations. In the majority of patients with CD19- and
      myeloid antigen-positive acute leukemia, subpopulations of blast cells with this
      mixed phenotype were detected during morphologic remission.

PMID- 7522297
TI  - Tacrolimus ointment for atopic dermatitis.

PMID- 7522298
TI  - Nitric oxide synthesis in rat cardiac myocytes and fibroblasts.
AB  - We investigated nitric oxide (NO) synthase activity in cultured neonatal rat
      cardiac myocytes and fibroblasts upon treatment with interleukin 1 beta (IL-1
      beta) and lipopolysaccharide (LPS). Incubation of cardiac myocytes for 24 h with
      IL-1 beta or LPS caused a significant increase in NO and cGMP production.
      Simultaneous incubation of IL-1 beta with NG-monomethyl-L-arginine or
      transforming growth factor beta (TGF-beta) completely inhibited the IL-1 beta
      induced NO and cGMP production in cardiac myocytes. In contrast, incubation of
      cardiac fibroblasts for 24 h with IL-1 beta or LPS showed no significant effect
      on NO or cGMP production. Addition of IL-1 beta decreased the beating rate of
      cardiac myocytes, but TGF-beta overcame that inhibition. These observations
      suggest the presence of iNOS in cardiac myocytes, which is an important regulator
      of contractile function of the heart.

PMID- 7522302
TI  - Certification of poliomyelitis eradication--the Americas, 1994.
AB  - In May 1985, the Pan American Health Organization (PAHO) proposed the goal of
      interruption of wild poliovirus transmission in the Western Hemisphere by 1990
      (1). This proposal was endorsed by all member governments and was supported by
      several agencies and organizations, including Rotary International, the U.S.
      Agency for International Development, the United Nations Children's Fund, the
      Inter-American Development Bank, and the Canadian Public Health Association. On
      August 20, 1994, PAHO reported that 3 years had passed since the occurrence of
      the last case of poliomyelitis associated with wild poliovirus isolation in the
      Americas (Peru, August 1991) (2). This report summarizes the steps to certify
      eradication of polio in the Americas.

PMID- 7522301
TI  - [Surgical treatment of epileptogenic hemimegalencephaly].
AB  - Thirteen children affected by hemimegalencephaly were observed in the Pediatric
      Section of the Institute of Neurosurgery of the Catholic University of Rome in
      the last six years. Nine of them were operated because of an intractable
      epilepsy. Seven were males and 2 females; the age at operation ranged between 7
      months and 11 years (mean: three years and five months); the follow-up period
      varied between 1 and 6 years (mean 3 years and 10 months). All the patients had a
      clinical history of daily epileptic seizures not responsive to medical treatment;
      all of them presented with severely delayed psychomotor development. At
      neurological examination, six children showed a motor deficit of variable
      severity contralateral to the affected hemisphere and two patients a severe
      tetraparesis. The remaining child did not present with motor deficit. In all the
      cases the diagnosis had been obtained by CT scan and MRI. One of the cerebral
      hemispheres was abnormally enlarged with associated dilation of the lateral
      cerebral ventricle. The cortical architecture was obviously deranged with several
      areas of heterotopia of the gray substance suggesting an alteration of the
      neuronal cell migration. All the children underwent an extrathalamocaudato
      hemispherectomy. A post-operative ventriculo-peritoneal shunt was required in two
      cases. There were neither operative, nor late deaths. A dramatic reduction in the
      frequency and severity of epileptic seizures was observed in all but one of the
      patients of the series.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522300
TI  - Genetic aspects of Escherichia coli virulence.

PMID- 7522299
TI  - Role of protein kinase C in mediating NGF effect on neuropeptide Y expression in
      PC12 cells.
AB  - Neuropeptide Y (NPY) is a 36 amino acid peptide present in the central and
      peripheral nervous systems. Treatment with Nerve Growth Factor (NGF) induces an
      increase in NPY mRNA in PC12 cells, a rat pheochromocytoma cell line extensively
      used as a model of neuronal differentiation. Stimulators of both cAMP and calcium
      phospholipid dependent protein kinases (PKA and PKC respectively) increase NPY
      mRNA levels in a similar way to NGF. Nevertheless, H-89, a specific inhibitor of
      PKA failed to block NGF stimulated NPY mRNA accumulation. Furthermore, direct
      measurement of PKA activity in cell extracts showed no increase following NGF, in
      contrast to forskolin. H7, an inhibitor of both PKC and PKA systems completely
      abolished the NGF induced increase in NPY mRNA, suggesting that PKC is necessary
      for NGF induction of the NPY gene. NGF also increased PKC activity in cell
      extracts in a similar way to phorbol myristate acetate (PMA). Use of a reporter
      function, chloramphenicol acetyl transferase, controlled by 700 base pairs of the
      5' flanking region of the NPY gene demonstrated that NGF and phorbol ester
      stimulated transcription of the NPY gene. This stimulation could be blocked by
      pre-incubating PC12 cells with calphostin C, a specific inhibitor of PKC. Our
      results indicate that NGF induces NPY gene expression via activation of PKC
      system. Although an increase in adenylate cyclase activity affects the expression
      of the NPY gene, activation of PKA appears not to be involved in mediating the
      NGF effects.

PMID- 7522303
TI  - Immunophilins mediate the neuroprotective effects of FK506 in focal cerebral
      ischaemia.
AB  - The immunosuppressive action of the drug FK506 involves inhibition of calcineurin
      in T-lymphocytes by a complex of FK506 and an FK506 binding protein, FKBP12, a
      member of the immunophilin protein family. The functional role of brain
      immunophilins is, however, unclear. We show here that FK506 is a powerful
      neuroprotective agent in an in vivo model of focal cerebral ischaemia when
      administered up to 60 min post-occlusion. The minimum effective neuroprotective
      dose is comparable with the immunosuppressant dose in humans, suggesting that
      FK506 may have clinical potential for the treatment of stroke. Although the
      related immunosuppressants rapamycin and cyclosporin failed to reduce brain
      damage, the finding that rapamycin pretreatment blocked the effect of FK506
      confirms a role for immunophilins in the neuroprotective mechanism.

PMID- 7522304
TI  - Calcium signalling in T cells stimulated by a cyclophilin B-binding protein.
AB  - The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from
      the T-cell receptor (TCR) that normally leads to T-cell activation. When bound to
      cyclophilin, cyclosporin A binds and inactivates the key signalling intermediate
      calcineurin. To identify potential cellular homologues of cyclosporin A that
      might regulate calcium signalling, we have cloned human genes encoding
      cyclophilin B-binding-proteins using the yeast two-hybrid system. One gene
      product, when overexpressed in Jurkat T cells, specifically induced transcription
      from the interleukin-2 enhancer, by activating the T-cell-specific transcription
      factors NF-AT and NF-IL2A. This protein, termed calcium-signal modulating
      cyclophilin ligand (CAML), acts downstream of the TCR and upstream of calcineurin
      by causing an influx of calcium. CAML appears to be a new participant in the
      calcium-signal transduction pathway, implicating cyclophilin B in calcium
      signalling, even in the absence of cyclosporin.

PMID- 7522305
TI  - Competition for follicular niches excludes self-reactive cells from the
      recirculating B-cell repertoire.
AB  - Two different approaches to follow clones of B lymphocytes in a diverse preimmune
      repertoire reveal a new process for eliminating self-reactive cells in the
      periphery which depends on competition between cells with different
      specificities. A key feature of this censoring mechanism is the selective
      exclusion of self-antigen-binding B cells from the normal migration route into
      lymphoid follicles, resulting in their premature death. This is a striking
      example of homeostasis by cellular competition for limiting niches and may
      explain the paradoxical association between immunodeficiency and autoimmunity.

PMID- 7522306
TI  - Diagnostic significance and antigen specificity of antineutrophil cytoplasmic
      antibodies in renal diseases. A prospective multicentre study. Italian Group of
      Renal Immunopathology.
AB  - In a prospective multicentre study on the clinical significance of ANCA in renal
      diseases, sera from 920 patients with rapidly progressive renal failure and/or
      renal disease in association with extrarenal signs suggestive of a systemic
      vasculitis were tested for the presence of ANCA by indirect immunofluorescence
      (IIF) and ELISA. 193 of 920 cases (20.9%) were positive by IIF and 180 (19.5%) by
      ELISA, using a 'crude' cytoplasmic extract as substrate. The sensitivity and
      specificity of IIF for 'pauci-immune' cresentic necrotizing GN (CNGN), in
      association or not with systemic vasculitis, was 87.5 and 95.6% respectively. The
      IIF pattern and antigen specificity (alpha granules and MPO) correlated well with
      the clinical features: a cANCA pattern (alpha granules) was associated with ENT
      involvement (probable Wegener's granulomatosis); a pANCA pattern (MPO) with
      'idiopathic' CNGN and small-vessel vasculitis without respiratory tract disease
      (microscopic polyarteritis); patients with a pulmonary-renal syndrome had either
      c or pANCA in a similar proportion. Our study confirms a high sensitivity and
      specificity of ANCA for patients with CNGN. ANCA should be considered an
      important diagnostic test in patients with renal diseases, especially in the
      presence of rapidly progressive renal failure.

PMID- 7522307
TI  - Adynamic bone disease with negative aluminium staining in predialysis patients:
      prevalence and evolution after maintenance dialysis.
AB  - Aplastic bone disease (ABD) is a common form of renal osteodystrophy and is
      characterized by a defect in bone matrix formation and mineralization without an
      increase in osteoid thickness. The prevalence and pathogenesis of ABD in
      predialysis patients is largely unknown. We prospectively studied 92 unselected
      predialysis patients with a creatinine clearance < 10 ml/min/1.73 m2 and a mean
      age of 45 +/- 2 years (61 M, 31 F). None of the study patients had received any
      form of vitamin D therapy, and CaCO3 was the primary phosphate binder. Aplastic
      bone disease was observed in 30 (32%) patients. Stainable bone aluminium surface
      was < 3% in all ABD patients. Patients with ABD were older (52 +/- 3 versus 42 +/
      2 years; P < 0.01) and had reduced serum intact PTH compared to non-ABD patients
      (199 +/- 25 versus 561 +/- 87 pg/ml; P < 0.001). Patients with diabetes mellitus
      showed lower PTH values (179 +/- 31 versus 432 +/- 62 pg/ml; P < 0.001) and a
      lower incidence of advanced hyperparathyroidism bone lesions (16% versus 46%; P <
      0.05) than non-diabetic patients. However, diabetes was not clearly associated
      with low bone turnover disease (56% in diabetics versus 41% in non-diabetics; P =
      0.1). A second bone biopsy was obtained in eleven ABD patients after a period of
      16.6 +/- 2.2 months on maintenance dialysis with a dialysate calcium of 7 mg/dl.
      Bone histology was unchanged in 10 patients, and one evolved to mild
      hyperparathyroidism. Trabecular bone volume did not change (22.7 +/- 1.7 versus
      20.7 +/- 1.7%), and the stainable bone aluminium surface remained < 3%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7522308
TI  - Time-dependent effects of acute chlorpyrifos administration on spatial delayed
      alternation and cholinergic neurochemistry in weanling rats.
AB  - On postnatal day 21 (PND21), Long-Evans rat pups received a single subcutaneous
      injection of either 0 (corn oil vehicle), 90, 120, or 240 mg/kg chlorpyrifos and
      were then tested for T-maze delayed alternation on PND23 or 26.
      Acetylcholinesterase (AChE) activity and muscaranic receptor density [i.e.,
      quinuclidinyl benzilate (QNB) binding] were determined in hippocampus and cortex
      of brains taken from pups 15 hours after the end of behavioral testing (i.e., the
      morning of PND24, and 27). Pups exposed to the 240 mg/kg dose of chlorpyrifos
      showed signs of overt toxicity that precluded behavioral testing. Exposure to the
      120 mg/kg dose produced a selective memory impairment (ie., a deficit in delayed
      alternation but not position discrimination) relative to the 90 mg/kg and vehicle
      groups. This impairment was transient, however, as it appeared on PND23 and was
      absent by PND26. PND21 exposure to chlorpyrifos produced dose-related inhibition
      and recovery of brain AChE over the PND24-27 age range. A similar pattern was
      observed in hippocampus. Binding of [3H]QNB was reduced in frontal cortex on
      PND27 only at the 240 mg/kg dose. No significant effects were observed in the
      hippocampus. These results suggest that the neurochemical effects of acute
      chlorpyrifos administration are more transient, and the behavioral effects are
      smaller and shorter-lived than what has been reported in adult rats.

PMID- 7522309
TI  - Stress and/or tranylcypromine treatment affects serotonergic measures in blood
      and brain in rats.
AB  - Since stress can alter serotonin (5-hydroxytryptamine, 5-HT) turnover in the
      brain and the periphery, the effects of different types of acute stress on
      serotonin and related substances in the whole blood and various brain areas in
      rats pretreated with tranylcypromine (TCP) were studied. TCP administered alone
      caused a rise in 5-HT, a fall in its metabolite (5-hydroxyindoleacetic acid, 5
      HIAA) in the whole blood and in every part of the brain analyzed relative to
      controls. In rats given TCP and subjected to footshock or water-immersion
      restraint stress similar changes, but to a different extent, were observed. 5-HT
      level remained essentially constant except in the blood and the limbic system,
      whereas 5-HIAA level was found to be increased in the blood and the brain, mainly
      in the limbic system and the brainstem following footshock. Water-immersion
      restraint stress caused an increase in 5-HT only in the limbic system without any
      changes in 5-HT and 5-HIAA in the blood. Relative to controls, an increase in
      total tryptophan concentration in the whole blood and in every part of the brain
      was found only after footshock application with or without pretreatment with TCP.
      In conclusion, responses to stress in rats may depend upon the type of stimulus
      applied as well as of a concurrent administration of TCP. Some regional
      differences may account for an altered in vivo efficacy of this drug.

PMID- 7522314
TI  - Ultrastructural analysis of tyrosine hydroxylase-, substance P-, and calcitonin
      gene-related peptide-immunoreactive nerve fibers in the rat iris.
AB  - Different patterns of distribution of chemically different nerve fibers in the
      rat iris were studied by immunoelectron microscopy. The iris was immunostained
      either singly for tyrosine hydroxylase (TH), or doubly for substance P (SP) and
      calcitonin gene-related peptide (CGRP), or triply for TH, SP and CGRP. TH
      positive fibers were distributed in the stroma near the iris dilator and within
      the iris sphincter. SP/CGRP-positive fibers were found mainly in the anterior
      half of the stroma and partly in the stroma close to the sphincter, but were
      hardly ever seen in the stroma near the dilator or within the sphincter. Fibers
      neither positive for TH, SP nor CGRP were observed in the stroma near the dilator
      and within the sphincter.

PMID- 7522313
TI  - Pure ovarian immature teratoma, a unique and curable disease: 10 years'
      experience of 32 prospectively treated patients.
AB  - OBJECTIVE: To report and evaluate a conservative and individualized treatment
      policy in a homogeneously selected series of patients affected by pure ovarian
      immature teratoma. METHODS: This prospective trial, with specific treatment
      policies according to stage and grade, was planned and started in 1982. The study
      population consisted of 32 patients affected by pure immature teratoma, with the
      exclusion of mixed germ cell tumors. Fertility-sparing surgery was performed
      whenever possible. Surgery alone, with careful follow-up, was adopted for stage I
      or II according to the International Federation of Gynecology and Obstetrics
      (FIGO) and grade 1 or 2 tumors. The other patients, with stage III or with grade
      3 stage I or II tumors, or those referred at relapse, were treated with platinum
      based chemotherapy regimens. RESULTS: Thirty of 32 patients underwent fertility
      sparing surgery. Ten of 32 patients received chemotherapy after surgery, either
      as adjuvant treatment or in the presence of visible tumor. All 32 patients are
      alive and disease-free, with a median follow-up from surgery of 47 months (range
      11-138). In six patients, regardless of the administration of chemotherapy, the
      tumor either spontaneously differentiated toward mature glia or increased in
      volume, mimicking progression but still remaining completely mature. Five of six
      patients wishing to procreate had a total of seven normal pregnancies.
      CONCLUSIONS: Pure ovarian immature teratoma is a potentially curable disease with
      a unique natural history. Our data substantiate the hypothesis that low-grade and
      low-stage tumors do not require chemotherapy, and that a fertility-sparing
      surgical approach is warranted in all cases.

PMID- 7522312
TI  - Epidemiologic predictors of hepatitis C virus infection in pregnant women.
AB  - OBJECTIVE: To identify sensitive epidemiologic predictors of a positive hepatitis
      C virus antibody test in asymptomatic persons, and to compare the cost of testing
      only persons with an epidemiologic predictor to that of universal screening.
      METHODS: Seventeen hundred consecutive pregnant women were tested by enzyme
      linked immunosorbent assay for antibody to hepatitis C virus. Seventy-five
      subjects tested positive and were compared with 257 pregnant women who tested
      negative. Cohort and control patients were interviewed and their medical records
      were reviewed to identify those with chosen predictors of a positive hepatitis C
      virus antibody test. RESULTS: Seventy-four of 75 cohort patients and 108 of 257
      controls had one or more predictors of a positive antibody test. Cohort patients
      were significantly more likely (P < .001) to have the following: human
      immunodeficiency virus infection, a sex partner with a risk factor for hepatitis,
      age greater than 30 years, and a history of drug use, blood transfusion, sexually
      transmitted disease, hepatitis, or incarceration. The sensitivity and specificity
      of a single predictor in identifying a person with a positive test were 99 and
      58%, respectively. The cost of finding a single individual with a positive
      antibody test by universal screening was $674, compared to $303 by selectively
      screening persons with one or more predictors of a positive antibody test.
      CONCLUSIONS: Most individuals with positive hepatitis C virus antibody tests can
      be identified on the basis of epidemiologic predictors, reducing the cost of
      testing by 55%. These patients may receive appropriate medical therapy, and their
      children may be evaluated for possible infection by vertical transmission of
      hepatitis C virus.

PMID- 7522310
TI  - Cranial nerves and brain fiber systems of the medaka fry as observed by a whole
      mount staining method.
AB  - The cranial nerves and the brain fiber systems of the medaka (Oryzias latipes)
      fry are revealed by a whole-mount staining method. Newly hatched fry of an albino
      strain of the medaka were fixed, partially digested with trypsin, treated in 1%
      Triton X-100, and finally immunohistochemically stained using anti-neurofilament
      protein (70K+160K+210K) antibodies. Since both head skin and eyes were colorless
      in the albino fish, the three-dimensional distribution of of nerve fibers in the
      brain could be readily observed in whole specimens without interference of
      pigment cells. All cranial nerves and main fiber systems in the adult fish were
      differentiated in the fry brain. Using this method, the distribution of nerves to
      the ocular muscles and the periorbital pit organs was shown.

PMID- 7522311
TI  - The immunobiology and obstetrical consequences of antiphospholipid antibodies.
AB  - Two classes of antiphospholipid antibodies (APA) are associated with adverse
      pregnancy outcomes. Those APA identified by immunoassays using phospholipid
      coated surfaces (e.g., anticardiolipin antibodies) seem to bind to the 57 kD
      anticoagulant protein, beta 2-glycoprotein-I, when complexed with anionic
      phospholipid bilayers. Such APA may or may not prolong phospholipid-dependent
      clotting assays. A second class of APA are identified by their interference with
      phospholipid-dependent clotting assays (i.e., lupus anticoagulants). The latter
      bind to phospholipids present in a unique hexagonal phase either alone or
      complexed with prothrombin or beta 2-glycoprotein-I. There is evidence that both
      classes of APA are directly responsible for adverse pregnancy outcomes including
      spontaneous abortions, stillbirths, fetal growth retardation, thrombosis,
      thrombocytopenia, and preeclampsia. Putative APA-mediated pathogenic mechanisms
      include intervillous thrombosis, intravillous infarctions and decidual
      vasculopathy. The thrombogenicity of APA may result from their interference with
      endothelial phospholipids required for antithrombin III and protein C and S
      anticoagulant activity and prostacyclin synthesis and/or increased endothelial
      expression of the procoagulants: tissue factor, von Willebrand factor, platelet
      activating factor, and plasminogen activator inhibitor type-1. Other
      prothrombotic properties seem to include: increased platelet aggregation, and
      reduced beta 2-glycoprotein-1 and annexin V anticoagulant activity. Rigorous
      diagnostic criteria must be applied to the detection of both classes of APA
      because the prevention of adverse pregnancy outcomes requires potentially
      hazardous anticoagulant therapy.

PMID- 7522316
TI  - Hepatocellular carcinoma metastasizing to the brain and orbit: report of three
      cases.
AB  - Hepatocellular carcinoma rarely metastasizes to the brain or orbit. We report 3
      clinically manifest examples, one of which occurred in a 13-yr-old boy. In 2
      cases the intracranial metastasis was the initial presenting lesion. The 2 cases
      of brain metastasis both presented with intracerebral hemorrhage. Light
      microscopic examination of these tumors revealed a trabecular hepatocellular
      carcinoma of Edmondson grade II with focal hemorrhage and necrosis. Their
      immunohistochemical profile was identical to that described for primary
      hepatocellular carcinoma. The differential diagnosis from other intracranial
      metastatic tumors is discussed.

PMID- 7522317
TI  - Short-term diethylnitrosamine-induced oval cell responses in three strains of
      mice.
AB  - The oval cells of the liver have been identified as target cells of chemical
      carcinogens during rat hepatocarcinogenesis and are believed to act as liver stem
      cells. In this study mice (strains C3H/EJ (C3H), C57/BL6J (C57) and hybrid B6C3F1
      (F1)) were sacrificed at 1, 3 and 7 days after administration of a single dose of
      the carcinogen diethylnitrosamine (DEN), and histopathological studies of oval
      cells were evaluated using Haematoxylin and Eosin (H&E), Picro-Mallory (P-M),
      alpha-fetoprotein (A-FP) and glutathione S-transferase placental form (GST-pi)
      staining techniques and electron microscopy (EM). Increased oval cell
      proliferation was observed as soon as one day following exposure of the mice to
      DEN, in a manner consistent with C3H and C57 mice exhibiting high and low
      susceptibility to DEN respectively, with hybrid F1 mice being intermediate in DEN
      sensitivity. This analysis indicates that, in mice, oval cells are target cells
      at very early stages of liver carcinogenesis and supports the notion that oval
      cells are potential liver stem cells.

PMID- 7522318
TI  - Comparison of Pneumocystis carinii detection by toluidine blue O staining, direct
      immunofluorescence and DNA amplification in sputum specimens from HIV positive
      patients.
AB  - Pneumocystis carinii pneumonia (PCP) is the commonest opportunistic infection in
      AIDS patients. By using the polymerase chain reaction (PCR), specific DNA
      sequences can be amplified and used in diagnosis of infections such as PCP where
      the causative pathogen is both difficult to grow and present in low numbers.
      Twenty HIV positive patients were investigated for PCP. Twenty sputa (15 induced
      and 5 expectorated) had toluidine blue O staining, direct immunofluorescence and
      PCR performed for Pneumocystis carinii in a blinded fashion. PCR was performed
      using primers pAZ102-E 5' GATGGCTGTTTCCAAGCCCA 3' and pAZ102-H 5'
      GTGTACGTTGCAAAGTACTC 3' from the gene coding for Pneumocystis carinii
      mitochondrial ribosomal RNA with a specific 346 base-pair sequence being
      amplified from positive specimens. Ten of the patients had Pneumocystis carinii
      shown by conventional tests and PCR. Another 3 patients were positive only by
      PCR, all had evidence of infection with Pneumocystis carinii; the first was
      positive by subsequent conventional stains, the second was treated for bacterial
      bronchitis but had a non-resolving chest infection with PCP found on postmortem
      after 4 mths, the third had a typical interstitial infiltrate on CXR and
      responded to empiric PCP treatment. PCR is more sensitive than toluidine blue O
      staining and direct immunofluorescence in detecting Pneumocystis carinii in
      sputum from HIV patients and may become the diagnostic method of choice for PCP.

PMID- 7522319
TI  - In vitro suppression of Pseudomonas cepacia after limited exposure to
      subinhibitory concentrations of amiloride and 5-(N,N-hexamethylene) amiloride.
AB  - Amiloride (A) for aerosolized therapy in cystic fibrosis (CF) is under
      investigation. Antipseudomonal properties of A and A analogs in vitro have
      recently been described. This study was performed to determine if there was
      suppression of P. cepacia growth after a limited 2-hour exposure to
      (subinhibitory) concentrations of A +/- tobramycin (T) or to the analog 5-(N,N
      hexamethylene) amiloride (HMA) in vitro. The MIC of each drug against five
      different P. cepacia strains was determined. Cells were prepared in Mueller
      Hinton broth to [10(6)] colony forming units (CFU)/mL and incubated at 35 degrees
      C for 2 hours in the presence and absence of subinhibitory A, HMA, T, or A+T. The
      CFU were measured before and at 1-hour intervals after dilutional removal of
      drug. The post-antibiotic effect (PAE) was defined as the time (in minutes)
      required for the test culture counts to increase 10-fold minus the time required
      for control counts to increase 10-fold. At 400 micrograms/mL or 200
      micrograms/mL, the PAE for A against five different strains was 139 +/- 23 and 83
      +/- 24 (mean +/- SD) minutes, respectively. For 100 micrograms/mL and 50 mu cg/mL
      HMA, the PAE was 122 +/- 38 and 65 +/- 25 minutes. For T and A+T (200
      micrograms/mL + 32 micrograms/mL) the PAE ws 168 +/- 30 and 258 +/- 30 minutes.
      We conclude that A and the analog HMA in (subinhibitory) concentrations have a
      suppressive effect on P. cepacia after drug removal and potentiate the effect of
      T in vitro.

PMID- 7522315
TI  - The effects of topical corticosteroids and plasmin inhibitors on refractive
      outcome, haze, and visual performance after photorefractive keratectomy. A
      prospective, randomized, observer-masked study.
AB  - BACKGROUND: This study of 86 patients with 12 months of follow-up was designed to
      determine whether topical corticosteroids or plasmin inhibitors have an effect on
      the outcome of photorefractive keratectomy. METHODS: Patients were allocated
      randomly to either steroid (0.1% fluorometholone for 6 months), plasmin-inhibitor
      (aprotinin 40 IU/ml for 3 weeks), or control (no treatment) groups and underwent
      either -3.00- or -6.00-diopter (D) corrections. RESULTS: With -3.00-D
      corrections, the mean refractive change was significantly greater at 3 and 6
      months (P < 0.05) in the steroid group compared with the control group. When
      steroids were discontinued, the difference became insignificant within 3 months.
      Similarly, with -6.00-D procedures the mean refractive change was greater at 6
      weeks and 3 and 6 months (P < 0.01), but the refractive change again became
      insignificant 3 months after stopping steroid treatment. Four patients treated
      with steroids had a hyperopic shift greater than +2.00 D of that intended at 12
      months. Similar overcorrections were not noted in the other treatment groups.
      There were no differences in refractive outcome between the aprotinin and control
      groups at any stage. With -6.00-D procedures, objective measurements of haze were
      significantly greater in the aprotinin group compared with the control group at 9
      and 12 months (P < 0.05). With this exception, there were no differences in haze,
      forward or backward scatter of light, best-corrected visual acuity, or halo
      measurements between the groups. CONCLUSIONS: Corticosteroids can maintain a
      hyperopic shift during their administration, but this effect is reversed on
      cessation of treatment. Objective tests have shown that steroids have no effect
      on corneal haze or visual performance after PRK. There is no justification for
      routinely submitting all patients to long-term steroid regimens and their
      associated side effects. Treatment with aprotinin produced no beneficial effect
      on refractive outcome, and haze was greater in the -6.00-D procedures. The
      concept of modulating the plasminogen activator/plasmin system to regulate wound
      healing after PRK is discussed.

PMID- 7522320
TI  - Hospice nursing. The concept of palliative care.
AB  - In this article, some differences are presented between hospice and home care
      nurses. Issues related to pain control, symptom management, and dehydration are
      highlighted. Emphasis is placed on the spiritual dimensions of hospice care and
      the holism implicit in its concept.

PMID- 7522322
TI  - Omega 3 polyunsaturated fatty acid modulates dihydropyridine effects on L-type
      Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes.
AB  - The effect of docosahexaenoic acid (DHA; C22:6) on dihydropyridine (DHP)
      interaction with L-type Ca2+ channel current (ICa), cytosolic Ca2+ (Cai), and
      cell contraction in isolated adult rat cardiac myocytes was studied. The DHP L
      type Ca(2+)-channel blocker nitrendipine (10 nM) reduced peak ICa (measured by
      whole-cell voltage clamp from -45 to 0 mV) and reduced the amplitude of the Ca2+
      transient (measured as the transient in indo-1 fluorescence, 410/490 nm) and the
      twitch amplitude (measured via photodiode array) during steady-state electrical
      stimulation (0.5 Hz). The DHP L-type Ca2+ channel agonist BAY K 8644 (10 nM)
      significantly increased ICa, the amplitude of the Cai transient, and contraction.
      When cells were exposed to DHA (5 microM) simultaneously with either BAY K 8644
      or nitrendipine, the drug effects were abolished. Arachidonic acid (C20:4) at 5
      microM did not block the inhibitory effects of nitrendipine nor did it prevent
      the potentiating effects of BAY K 8644. DHA modulation of DHP action could be
      reversed by cell perfusion with fatty acid-free bovine serum albumin at 1 mg/ml.
      Neither DHA nor arachidonic acid alone (5 microM) had any apparent effect on the
      parameters measured. DHA (5 microM) had no influence over beta-adrenergic
      receptor stimulation (isoproterenol, 0.01-1 microM)-induced increases in ICa,
      Cai, or contraction. The findings that DHA inhibits the effect of DHP agonists
      and antagonists on Ca(2+)-channel current but has no effect alone or on beta
      adrenergic-induced increases in ICa suggests that DHA specifically binds to Ca2+
      channels at or near DHP binding sites and interferes with ICa modulation.

PMID- 7522321
TI  - P-selectin induces the expression of tissue factor on monocytes.
AB  - P-selectin on activated platelets and stimulated endothelial cells mediates cell
      adhesion with monocytes and neutrophils. Since activated platelets induce tissue
      factor on mononuclear leukocytes, we examined the effect of P-selectin on the
      expression of tissue factor activity in monocytes. Purified P-selectin stimulated
      tissue factor expression on mononuclear leukocytes in a dose-dependent manner.
      Chinese hamster ovary (CHO) cells expressing P-selectin stimulated tissue factor
      procoagulant activity in purified monocytes, whereas untransfected CHO cells and
      CHO cells expressing E-selectin did not. Anti-P-selectin antibodies inhibited the
      effects of purified P-selectin and CHO cells expressing P-selectin on monocytes.
      Incubation of CHO cells expressing P-selectin with monocytes leads to the
      development of tissue factor mRNA in monocytes and to the expression of tissue
      factor antigen on the monocyte surface. These results indicate that P-selectin
      upregulates the expression of tissue factor on monocytes as well as mediates the
      binding of platelets and endothelial cells with monocytes and neutrophils. The
      binding of P-selectin to monocytes in the area of vascular injury may be a
      component of a mechanism that initiates thrombosis.

PMID- 7522323
TI  - Integrin alpha v beta 3 rescues melanoma cells from apoptosis in three
      dimensional dermal collagen.
AB  - Human melanoma cells required ligation of the integrin alpha v beta 3 to sustain
      viability and growth in three-dimensional dermal collagen. Variant melanoma
      cells, lacking the alpha v subunit, progressed rapidly to apoptosis within this
      matrix, whereas transfection of these cells with an alpha v cDNA restored alpha v
      beta 3 expression and prevented apoptosis. Furthermore, inhibition of alpha v
      beta 3 ligation with a monoclonal antibody promoted cell death. Apoptosis of
      alpha v(-) cells within this matrix could be overcome by the addition of insulin
      or serum. However, alpha v(+) melanoma cells had a significant growth advantage
      in the presence of these growth factors. Initial adhesion of the melanoma cells
      to type I collagen depended on ligation of alpha 2 beta 1, but these cells can
      degrade this collagen to expose cryptic alpha v beta 3 binding sites. These
      findings provide evidence that the survival and growth of transformed cells may
      be regulated by collagen degradation and integrin-dependent anchorage to this
      proteolysed matrix.

PMID- 7522325
TI  - Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers
      increased sensitivity to cAMP.
AB  - Olfactory receptor neurons respond to odorant stimulation with a rapid increase
      in intracellular cAMP that opens cyclic nucleotide-gated (cng) cation channels.
      cng channels in rat olfactory neurons are activated by cAMP in the low micromolar
      range and are outwardly rectifying. The cloned rat olfactory cng channel
      (rOCNC1), however, is much less sensitive to cAMP and exhibits very weak
      rectification. Here we describe the cloning and characterization of a second rat
      cng channel subunit, denoted rOCNC2. rOCNC2 does not form functional channels
      when expressed alone. When rOCNC1 and rOCNC2 are coexpressed, however, an
      outwardly rectifying cation conductance with cAMP sensitivity near that of the
      native channel is observed. In situ hybridization with probes specific for the
      two subunits shows that they are coexpressed in olfactory receptor neurons. These
      data indicate that the native olfactory cng channel is likely to be a
      heterooligomer of the rOCNC1 and rOCNC2 subunits.

PMID- 7522326
TI  - Direct observation of substance P-induced internalization of neurokinin 1 (NK1)
      receptors at sites of inflammation.
AB  - Substance P (SP) can cause plasma leakage at sites of inflammation by binding to
      neurokinin type 1 (NK1) receptors on the surface of endothelial cells.
      Internalization after ligand binding could reduce the number of NK1 receptors on
      the cell surface and thus participate in the desensitization and resensitization
      of the inflammatory response to SP. By using an antibody to the receptor, we
      directly observed SP-induced internalization of NK1 receptors into endosomes in
      endothelial cells of postcapillary venules in the rat tracheal mucosa. In the
      absence of SP, an average of 15 immunoreactive endosomes were present per
      endothelial cell. After an intravenous injection of SP, the number of
      immunoreactive endosomes peaked at 107 per cell at 3 min and gradually returned
      to the baseline by 120 min. In parallel experiments we observed that when
      cultured cells transfected with the NK1 receptor were exposed to rhodamine-SP and
      an antibody to an extracellular Flag epitope of the NK1 receptor, the SP was
      internalized with the receptor antibody. Both in the cultured cells and in the
      endothelial cells of intact animals, the prompt SP-induced internalization was
      accompanied by rapid, long-lasting desensitization to SP. These studies suggest
      that internalization of NK1 receptors by endothelial cells may be one of the
      mechanisms that limit the amount of plasma leakage at sites of inflammation.

PMID- 7522324
TI  - Activated Ki-Ras complements erythropoietin signaling in CTLL-2 cells, inducing
      tyrosine phosphorylation of a 160-kDa protein.
AB  - We have previously shown that expression of erythropoietin (EPO) receptor (EPOR)
      alone failed to confer EPO responsiveness on the interleukin 2-dependent T-cell
      line CTLL-2, whereas the introduction of the EPOR into interleukin 3-dependent
      pro-B-cell lines, such as BAF-B03, allowed the cells to proliferate in response
      to EPO. Here, we report that additional expression of v-Ki-Ras conferred EPO
      dependent growth on CTLL-2 cells expressing the EPOR, with additional formation
      of a high-affinity EPOR. To investigate possible mechanisms of EPOR downstream
      signaling induced by v-Ki-Ras expression in these CTLL-2-derived cells, we
      carried out anti-phosphotyrosine immunoblot analysis of the EPOR complex
      immunoprecipitated with anti-EPOR antibody from lysates of cells with and without
      cytokine stimulation, revealing two 160-kDa and 130-kDa phosphotyrosyl proteins.
      An anti-JAK2 antibody did not react with these proteins, suggesting that they may
      represent cellular components involved in an EPO-EPOR signaling pathway induced
      by v-Ki-Ras. Similar phosphotyrosyl proteins were present among Friend
      erythroleukemia cell lines, in which the Friend virus gp55/EPOR complex on the
      cell surface constitutively sends signals for cell growth.

PMID- 7522327
TI  - Regulation of collecting duct water channel expression by vasopressin in
      Brattleboro rat.
AB  - AQP-CD is a vasopressin-regulated water channel expressed exclusively in the
      renal collecting duct. We have previously shown that AQP-CD is present in the
      apical plasma membrane and subapical vesicles of collecting duct cells,
      consistent with membrane-shuttling mechanisms that have been proposed to explain
      the short-term action of [Arg8] vasopressin (AVP) to regulate apical water
      permeability. We propose here that AVP may also have long-term actions on the
      collecting duct to regulate the expression of the AQP-CD water channel. We used
      immunoblotting, immunohistochemistry, and in vitro perfusion of renal tubules to
      investigate water channel regulation in collecting ducts of diabetes insipidus
      (Brattleboro) rats treated with a 5-day infusion of AVP or vehicle.
      Immunoblotting and immunohistochemistry demonstrated that collecting ducts of
      vehicle-infused Brattleboro rats had markedly reduced expression of AQP-CD
      relative to normal rats. In response to AVP infusion there was a nearly 3-fold
      increase in AQP-CD expression as detected by immunoblotting. Immunocytochemistry
      demonstrated that the increased expression was predominantly in the apical plasma
      membrane and subapical vesicles of collecting duct cells. Inner medullary
      collecting ducts of AVP-infused Brattleboro rats displayed a 3-fold increase in
      osmotic water permeability relative to vehicle-infused controls, in parallel with
      the change in AQP-CD expression. Based on these findings, we conclude that (i)
      long-term infusion of AVP, acting either directly or indirectly, regulates
      expression of the AQP-CD water channel and (ii) AQP-CD is the predominant AVP
      regulated water channel.

PMID- 7522328
TI  - An in vitro polysome display system for identifying ligands from very large
      peptide libraries.
AB  - We have used an in vitro protein synthesis system to construct a very large
      library of peptides displayed on polysomes. A pool of DNA sequences encoding
      10(12) random decapeptides was incubated in an Escherichia coli S30 coupled
      transcription/translation system. Polysomes were isolated and screened by
      affinity selection of the nascent peptides on an immobilized monoclonal antibody
      specific for the peptide dynorphin B. The mRNA from the enriched pool of
      polysomes was recovered, copied into cDNA, and amplified by the polymerase chain
      reaction (PCR) to produce template for the next round of in vitro synthesis and
      selection. A portion of the amplified template from each round was cloned into a
      filamentous phagemid vector to determine the specificity of peptide binding by
      phage ELISA and to sequence the DNA. After four rounds of affinity selection, the
      majority of clones encoded peptides that bound specifically to the antibody and
      contained a consensus sequence that is similar to the known epitope for the
      antibody. Synthetic peptides corresponding to several of these sequences have
      binding affinities ranging from 7 to 140 nM. The in vitro system described here
      has the potential to screen peptide libraries that are three to six orders of
      magnitude larger than current biological peptide display systems.

PMID- 7522330
TI  - The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein
      kinase C.
AB  - Bruton tyrosine kinase (EC 2.7.1.112) [Btk, encoded by Btk in mice and BTK in
      humans (formerly known as atk, BPK, or emb)], which is variously mutated in
      chromosome X-linked agammaglobulinemia patients and X-linked immunodeficient
      (xid) mice, has the pleckstrin homology (PH) domain at its amino terminus. The PH
      domain of Btk expressed as a bacterial fusion protein directly interacts with
      protein kinase C in mast cell lysates. Evidence was obtained that Btk is
      physically associated with protein kinase C in intact murine mast cells as well.
      Both Ca(2+)-dependent (alpha, beta I, and beta II) and Ca(2+)-independent protein
      kinase C isoforms (epsilon and zeta) in mast cells interact with the PH domain of
      Btk in vitro, and protein kinase C beta I is associated with Btk in vivo. Btk
      served as a substrate of protein kinase C, and its enzymatic activity was down
      regulated by protein kinase C-mediated phosphorylation. Furthermore, depletion or
      inhibition of protein kinase C with pharmacological agents resulted in an
      enhancement of the tyrosine phosphorylation of Btk induced by mast cell
      activation.

PMID- 7522329
TI  - Phosphatase inhibitors activate normal and defective CFTR chloride channels.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel
      is regulated by phosphorylation and dephosphorylation at multiple sites. Although
      activation by protein kinases has been studied in some detail, the
      dephosphorylation step has received little attention. This report examines the
      mechanisms responsible for the dephosphorylation and spontaneous deactivation
      ("rundown") of CFTR chloride channels excised from transfected Chinese hamster
      ovary (CHO) and human airway epithelial cells. We report that the alkaline
      phosphatase inhibitors bromotetramisole, 3-isobutyl-1-methylxanthine,
      theophylline, and vanadate slow the rundown of CFTR channel activity in excised
      membrane patches and reduce dephosphorylation of CFTR protein in isolated
      membranes. It was also found that in unstimulated cells, CFTR channels can be
      activated by exposure to phosphatase inhibitors alone. Most importantly, exposure
      of mammalian cells to phosphatase inhibitors alone activates CFTR channels that
      have disease-causing mutations, provided the mutant channels are present in the
      plasma membrane (R117H, G551D, and delta F508 after cooling). These results
      suggest that CFTR dephosphorylation is dynamic and that membrane-associated
      phosphatase activity may be a potential therapeutic target for the treatment of
      cystic fibrosis.

PMID- 7522331
TI  - CNQX infused into entorhinal cortex blocks memory expression, and AMPA reverses
      the effect.
AB  - Rats were trained in a step-down inhibitory avoidance task using a 0.8-mA foot
      shock and tested for retention 26 days later. Three to five days prior to the
      retention test they were bilaterally implanted with cannulae aimed at the
      entorhinal cortex. Ten minutes before testing they received an infusion, into the
      entorhinal cortex, of vehicle, ciano-nitro-quinoxaline-dione (CNQX; 0.5
      micrograms), amino-hydroxy-methyl-isoxalone-propionate (AMPA; 1.0 or 2.5
      micrograms), or AMPA (1.0 micrograms) plus CNQX (0.5 micrograms). CNQX blocked
      memory expression; the effect lasted less than 90 min. AMPA had no effect of its
      own, but at the lower dose level it counteracted the depressant influence of
      CNQX. It is not likely that the effect of CNQX could have been due to an
      influence on performance: In separate sets of experiments the bilateral
      intraentorhinal infusion of CNQX (0.5 micrograms) 10 min before training did not
      affect either acquisition or retention of the avoidance task or general activity
      during 3 min of free exploration in the training box. The results indicate that
      the integrity of AMPA receptors in the entorhinal cortex is necessary for memory
      expression.

PMID- 7522332
TI  - Endothelin-1 inhibits inward rectifier potassium channels and activates
      nonspecific cation channels in cultured endothelial cells.
AB  - A predominant inward rectifier and a small outward potassium current were
      obtained in whole-cell patch-clamp recordings from cultured bovine pulmonary
      arterial endothelial cells. Application of endothelial-1 (ET-1; 10-100 nmol/l)
      inhibited the inward rectifier. Washout with bath solution did not recover the
      current decreased by ET-1. In cell-attached studies, ET-1 (1 nmol/l) inhibited
      single-channel activity of the inward rectifier and in some patches enhanced
      activity of the outward potassium current without change of conductance. A non
      specific cation current which is permeable to calcium was identified in cell
      attached patches in cultured human umbilical vein endothelial cells. ET-1 (1
      nmol/l) increased activity of the nonspecific cation channel. ET-1 may increase
      calcium influx into endothelial cells and promote synthase and release of
      endothelium-derived factors.

PMID- 7522333
TI  - Stress, depression and schizophrenia in view of psychoimmunology.
AB  - The authors discuss the influence of stress on the immunological system. They
      describe changes in this system in depressive and in schizophrenic patients and
      analyze the eventual effect of these changes in the pathogenesis of endogenous
      psychopathology. The authors conclude that despite the fact that research into
      the immunology of these aspects are in the beginning stages, the data so far
      collected indicate a promising result.

PMID- 7522334
TI  - Ionic basis of GABAA receptor channel function in the nervous system.

PMID- 7522335
TI  - Exploiting heavy metal resistance systems in bioremediation.

PMID- 7522336
TI  - Dephosphorylation of nuclear non-histone proteins in submandibular glands of rats
      treated with isoproterenol.
AB  - Protein phosphatase that removed [32P]phosphate from non-histone proteins, i.e.,
      phenol-soluble acidic proteins, more rapidly and strongly than from histone
      proteins was present in nuclei of rat submandibular glands, but was not
      associated with chromatin. Cyclic AMP (10(-4)-10(-2) mM) stimulated the
      dephosphorylation of non-histone proteins, but not that of histone proteins.
      After a single injection of isoproterenol (IPR), the dephosphorylation of non
      histone proteins in rat submandibular gland nuclei increased within 15 min,
      reached a maximum in 30 min and returned to normal control levels within 4 h. The
      stimulation of dephosphorylation of non-histone proteins induced by IPR was not
      observed after prior treatment of the animals with dichloroisoproterenol. The
      dephosphorylation of histone proteins was not affected by the injection of IPR.
      Stimulation of beta-adrenoceptors with IPR in rat submandibular glands resulted
      in increase in cyclic AMP and decrease in RNA synthesis in the tissues in the
      first few hours after the injection. This decrease in RNA synthesis was temporary
      and was preceded by the increase in cyclic AMP level and in the dephosphorylation
      of non-histone acidic proteins in the tissues. These results suggest that protein
      phosphatase in nuclei plays an important part in the events controlling RNA
      synthesis by regulating the state of phosphorylation of non-histone acidic
      proteins. In addition, the phosphatase may be regulated by a function of the
      cytoplasmic membranes.

PMID- 7522337
TI  - [Polyarthritis, malabsorption and abdominal tumor].

PMID- 7522338
TI  - Surgical management of ovarian cancer.
AB  - Although several surgical approaches to the diagnosis and management of
      epithelial ovarian cancer are now standard, surprisingly few prospective data
      exist to support many of these procedures. However, retrospective data have
      accumulated over the past decade, much of it very recent, which allow clinicians
      to make informed decisions regarding most of the commonly performed procedures.
      This review is an attempt to critically evaluate the best available data
      regarding the following procedures: primary surgical staging, primary
      cytoreductive surgery, second look laparotomy and secondary cytoreductive
      surgery, and palliative surgery for relief of bowel obstruction. We conclude that
      there is evidence to support the continued use of primary surgical staging and
      primary cytoreductive surgery. However, data in support of second look laparotomy
      and secondary cytoreductive surgery are lacking, and we recommend that these
      procedures not be performed on a routine basis. Finally, we conclude that
      palliative surgery is hazardous at best and results in questionable benefits for
      most patients.

PMID- 7522341
TI  - [Enzymes: potent inhalant and ingestive allergens--obligation of declaration
      lacking in bakery products and flour].

PMID- 7522339
TI  - Keratin staining pattern in clinically normal and diseased oral mucosa of lichen
      planus patients.
AB  - The keratin pattern in oral epithelia is related to the type of terminal
      differentiation observed morphologically (keratinization/nonkeratinization) and
      to the presence or absence of epithelial dysplasia. Furthermore, it has been
      suggested recently that inflammatory phenomena influence the keratin expression
      in human gingiva. The aim of the present study was to describe the keratin
      pattern in oral lichen planus (OLP) lesions, which are well known to be
      characterized by hyperkeratinization and severe inflammatory changes, in order to
      elucidate the role of inflammation in keratin expression of oral epithelia.
      Tissue sections were stained with antikeratin antibodies directed to groups of
      keratins (AE1 and AE2) and to single keratin proteins (Nos. 5, 8, 13, and 19).
      The keratin pattern in OLP lesions differed in some respects from that of
      leukoplakias and frictional keratoses as characterized in previous studies. No
      consistent patterns for use in a diagnostic context were found. However, the
      changes in OLP lesions did not mimic those previously described in inflamed
      gingival specimens and in oral epithelial dysplasias. Thus, the results encourage
      further studies on the potential diagnostic use of keratin expression in
      premalignant oral lesions. Furthermore, the study suggests that the inflammatory
      reaction seen in OLP lesions does not influence keratin expression in a way
      comparable with the suggested influence of inflammation in gingival specimens.

PMID- 7522340
TI  - Effects of the beta-adrenoceptor antagonists atenolol and propranolol on human
      unstimulated whole saliva flow rate and protein composition.
AB  - The effects of 1-wk medication with two beta-adrenoceptor antagonists on
      unstimulated whole saliva flow rate and protein composition were evaluated in 11
      healthy young men in a randomized, double-blind, placebo-controlled, cross-over
      study. Unstimulated whole saliva was collected before each treatment period and
      then again after 7 days. The saliva was assessed for flow rate, total protein,
      and hexosamine and sialic acid concentrations and for amylase activity. No
      significant effect on saliva secretion rate was found. A statistically
      significant reduction of salivary total proteins was registered during atenolol
      medication. The amylase activity decreased significantly during treatment with
      both atenolol and propranolol. Significant changes of the calculated ratios of
      sialic acid/hexosamine and hexosamine/total protein indicated an alteration in
      glandular protein synthesis after atenolol treatment.

PMID- 7522343
TI  - Old protein provides new clue to nerve regeneration puzzle.

PMID- 7522342
TI  - [Prenatal diagnosis of umbilical cord hemangioma in increased alpha fetoprotein].
AB  - In a patient with elevated serum alpha-fetoprotein a little haemangioma of the
      umbilical cord is diagnosed by ultrasound in the 21st week of pregnancy. So far
      only nine reports exist of prenatal diagnosed haemangiomas of the cord. Severe
      complications like rupture, cord haematoma, non-immune hydrops fetalis and
      polyhydramnions as well as a perinatal mortality of 35% have been reported.
      Therefore, intensive surveillance during pregnancy is mandatory.

PMID- 7522345
TI  - Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase.
AB  - The proposal that nitric oxide (NO) or its reactant products mediate toxicity in
      brain remains controversial in part because of the use of nonselective agents
      that block NO formation in neuronal, glial, and vascular compartments. In mutant
      mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased
      significantly 24 and 72 hours after middle cerebral artery occlusion, and the
      neurological deficits were less than those in normal mice. This result could not
      be accounted for by differences in blood flow or vascular anatomy. However,
      infarct size in the mutant became larger after endothelial NOS inhibition by
      nitro-L-arginine administration. Hence, neuronal NO production appears to
      exacerbate acute ischemic injury, whereas vascular NO protects after middle
      cerebral artery occlusion. The data emphasize the importance of developing
      selective inhibitors of the neuronal isoform.

PMID- 7522344
TI  - Two identical noninteracting sites in an ion channel revealed by proton transfer.
AB  - The functional consequences of single proton transfers occurring in the pore of a
      cyclic nucleotide-gated channel were observed with patch recording techniques.
      These results led to three conclusions about the chemical nature of ion binding
      sites in the conduction pathway: The channel contains two identical titratable
      sites, even though there are more than two (probably four) identical subunits;
      the sites are formed by glutamate residues that have a pKa (where K(a) is the
      acid constant) of 7.6; and protonation of one site does not perturb the pKa of
      the other. These properties point to an unusual arrangement of carboxyl side
      chain residues in the pore of a cation channel.

PMID- 7522348
TI  - Palliative care: management of the patient with advanced cancer.
AB  - The incidence and mortality of cancer are increasing worldwide. Changes in
      lifestyle and living standards have contributed to this phenomenon, as have other
      factors, such as an increase in the high-risk elderly population in Western
      Europe and North America. This, coupled with the decline of the family unit and
      an escalation in the numbers of Americans living alone, is creating a significant
      health care problem in the United States; namely, how will we be able to provide
      adequate care for the increasing numbers of aged expected to develop cancer in
      the 21st century in ways compatible with cost-saving and cost-effective
      strategies currently being used in the health care industry? The bulk of current
      cancer research is directed at developing new curative strategies, while
      improving palliative measures for the treatment of the symptomatology of cancer
      is largely ignored. We will have to refocus our priorities if we are to be
      successful in addressing this problem. This paper provides an overview of current
      trends in the palliative management of patients with advanced cancer and offers
      insights into how we may begin to prepare ourselves to meet the challenges of
      cancer care in the years ahead.

PMID- 7522351
TI  - Significance of elevated pancreatic enzymes in intracranial bleeding.
AB  - Hyperamylasemia of pancreatic origin has been noted in patients with severe head
      injury without abdominal trauma or evidence of pancreatitis. Thirty-eight
      patients with intracranial bleeding of various types were evaluated for elevated
      pancreatic amylase and lipase enzymes without associated pancreatitis. Twenty
      five patients had elevated serum lipase; 17 of 25 also had elevated amylase
      without pancreatitis. Most lipase elevations occurred earlier than those of
      amylase. Six clinical variables--mannitol, ceftriaxone, nimodipine, steroids,
      Glasgow Coma Score, and total parenteral and enteral hyperalimentation--were
      evaluated to determine relationship to the enzyme elevations. A significant
      relationship exists between patients not treated with steroids and elevated
      lipase and amylase enzyme activities. Multivariate analysis revealed a
      significant interaction between lipase elevation and decreasing Glasgow Coma
      Score, indicative of increasing severity of intracranial bleeding. Proposed
      causes of enzyme elevations in intracranial bleeding include vagal stimulation,
      altered modulation of the central control of pancreatic enzyme release, and
      release of cholecystokinin from the brain. Physician awareness of the association
      of intracranial bleeding with the elevation of amylase and lipase without
      pancreatitis can save the patient needless cost and manipulation.

PMID- 7522349
TI  - Practical approaches to the treatment of patients with extensive stage small cell
      lung cancer.
AB  - Although initially extremely sensitive to many chemotherapeutic drugs and
      radiotherapy, ultimately small cell lung cancer (SCLC) is a progressive and fatal
      disease. Stage of disease is a major prognostic factor in the treatment of SCLC
      patients. Patients with limited stage disease have approximately a 10% chance of
      long-term (> 5 years) disease-free survival, whereas those with extensive stage
      disease are incurable with currently available therapy. In extensive stage
      disease, patients with a good performance status and younger than 65 years of age
      are ideal candidates for trials using intensive standard chemotherapy or
      experimental modalities; most patients, however, including those who are elderly
      and medically unfit, are best treated conservatively with single-agent etoposide.
      Various types of therapy, including intensive induction chemotherapy and
      consolidation regimens, have been unable to improve survival rates in extensive
      stage SCLC. Thus, until better treatments are developed, the goal of therapy for
      extensive stage SCLC should be adequate palliation and prolongation of quality
      survival.

PMID- 7522350
TI  - The community approach to salvage therapy for advanced head and neck cancer.
AB  - The natural history of squamous cell head and neck cancer is well understood.
      Locoregional approaches to salvage therapy for this disease have curative
      potential, primarily because distant metastases are uncommon. Before proceeding
      with salvage treatment, however, clinicians should identify the extent of disease
      and determine whether the treatment intent is curative or palliative. Because of
      the associated morbidity, surgery should be considered only in patients for whom
      cure of recurrent disease is feasible. Radiation therapy may be indicated in
      patients whose disease recurs after surgery and in selected patients in whom
      initial radiation has failed. Single-agent and combination chemotherapy, in
      particular the combination of cisplatin and 5-fluorouracil, has achieved overall
      response rates of 30% to 40% in patients with recurrent disease. However, cure
      after salvage chemotherapy has not been achieved. Until salvage treatment
      regimens capable of achieving significant long-term survival are identified,
      symptomatic palliation will remain the main treatment goal in this patient
      population.

PMID- 7522346
TI  - Padlock probes: circularizing oligonucleotides for localized DNA detection.
AB  - Nucleotide sequence information derived from DNA segments of the human and other
      genomes is accumulating rapidly. However, it frequently proves difficult to use
      such short DNA segments to identify clones in genomic libraries or fragments in
      blots of the whole genome or for in situ analysis of chromosomes. Oligonucleotide
      probes, consisting of two target-complementary segments, connected by a linker
      sequence, were designed. Upon recognition of the specific nucleic acid molecule
      the ends of the probes were joined through the action of a ligase, creating
      circular DNA molecules catenated to the target sequence. These probes thus
      provide highly specific detection with minimal background.

PMID- 7522352
TI  - Primary cerebellar yolk sac tumor: case report.
AB  - A rare case of cerebellar yolk sac tumor is described. A 4-year-old boy was
      admitted for the treatment of a cerebellar tumor and, following total removal of
      the tumor, he was treated with combination chemotherapy consisting of cisplatin,
      vinblastine, and bleomycin. He died 18 months after the primary diagnosis due to
      tumor recurrence. Serum alpha-fetoprotein level was well correlated with the
      clinical course and the amount of the tumor mass in neuroimaging.

PMID- 7522355
TI  - Aprotinin could promote arterial thrombosis in pigs: a prospective randomized,
      blind study.
AB  - Haemostatic properties of aprotinin could be associated with an increased risk of
      thrombosis. A randomized, blinded study was conducted to consider the potential
      thrombogenicity of aprotinin, using the Folts' model on femoral arteries in 12
      pigs. The flow variations were measured by a pulsed Doppler in anaesthetised
      animals. Ear immersion bleeding time was performed. During the first part of the
      study, a stenosis was performed successively on both femoral arteries, each for a
      period of 30 min, without prior injury, to assess the integrity of the vessel,
      and to check that the arteries did not develop cyclic flow reductions (CFR),
      permanent cessation of flow (PCF) or partial thrombosis, when a stenosis is
      applied. Then the clamp was released and a bolus of placebo (saline), or
      aprotinin (4 millions KIU, followed by a continuous infusion of 1 million KIU.h
      1), was administered. At the end of the bolus, the second part of the study
      began. Stenosis was applied to the arteries. If CRF, PCF, or partial thrombosis
      were observed without prior injury then the infused drug (aprotinin or saline)
      was considered a prothrombotic drug, and the opposite artery was studied. For
      each animal, right and left femoral artery segments were fixed and studied
      (morphologic study). Eighteen arteries were studied. In the aprotinin group, 6
      arteries out of 8 developed an unexpected thrombosis, as compared with only 2 out
      of 10 arteries in the control group (p = 0.02). The morphologic study confirmed
      the occurrence of thrombosis in 4 out of 7 arteries in the aprotinin group, as
      compared with only 1 out of 9 in the control group.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7522353
TI  - Effect of antibiotic treatment on inflammatory markers and lung function in
      cystic fibrosis patients with Pseudomonas cepacia.
AB  - BACKGROUND: The acquisition of Pseudomonas cepacia in patients with cystic
      fibrosis is associated with increasing deterioration in lung function and more
      frequent hospital admissions. Pseudomonas cepacia is usually resistant to several
      antibiotics in vitro, but the response of patients colonised with the organism
      has not been extensively studied in vivo. METHODS: A three month prospective
      study was performed to investigate the response of 14 Ps cepacia positive
      patients and 10 Ps cepacia negative patients to a two week course of intravenous
      antibiotics. All those who were Ps cepacia negative and six of the 14 Ps cepacia
      positive patients had Ps aeruginosa in their sputum which was sensitive to the
      prescribed therapy. The inflammatory markers C-reactive protein, white blood cell
      count, serum lactoferrin, neutrophil elastase/alpha 1-antitrypsin complex, and
      tumour necrosis factor alpha were measured at the start and end of each
      antibiotic course. RESULTS: The median (range) % improvement in baseline FEV1 and
      FVC following treatment in the group as a whole was 15.2% (-23.5% to 156.3%) and
      23.9% (-36.8% to 232.7%) respectively. There was no statistical difference in
      improvement in lung function, body weight, or inflammatory markers between
      individuals who were Ps cepacia positive and those who were Ps cepacia negative.
      CONCLUSIONS: Patients who are Ps cepacia positive appear to respond as well to
      intravenous antibiotics as those who are Ps cepacia negative, despite having
      lower lung function and a bacterium in their sputum which is resistant in vitro
      to the antibiotics used.

PMID- 7522354
TI  - Reversible inhibition of human platelet activation by hypothermia in vivo and in
      vitro.
AB  - A hypothermia-induced hemorrhagic diathesis is associated with cardiopulmonary
      bypass, major surgery, and multiple trauma, but its pathophysiological basis is
      not well understood. We examined the hypothesis that hypothermia reversibly
      inhibits human platelet activation in vitro and in vivo. Platelet activation was
      studied in normal volunteers by whole blood flow cytometric analysis of
      modulation of platelet surface GMP-140 and the glycoprotein (GP) Ib-IX complex
      in: a) shed blood emerging from a standardized in vivo bleeding time wound; b)
      peripheral blood activated in vitro with either thrombin (in the presence of gly
      pro-arg-pro, an inhibitor of fibrin polymerization) or the stable thromboxane
      (TX) A2 analogue U46619. Platelets in peripheral whole blood were activated at
      temperatures between 22 degrees C and 37 degrees C. the forearm skin temperature
      was maintained at temperatures between 22 degrees C and 37 degrees C prior to and
      during the bleeding time incision. Platelet aggregation was studied in shed blood
      by flow cytometry and in peripheral blood by aggregometry. Generation of TXB2
      (the stable metabolite of TXA2) was determined by radioimmunoassay. In vitro,
      hypothermia inhibited both thrombin- and U46619-induced upregulation of GMP-140,
      downregulation of the GPIb-IX complex, platelet aggregation, and TXB2 generation.
      These inhibitory effects of hypothermia were all completely reversed by rewarming
      the blood to 37 degrees C. In vivo, platelet activation was inhibited by
      hypothermia as shown by 5 independent assays of shed blood: upregulation of GMP
      140, downregulation of the GPIb-IX complex, platelet aggregate formation, TXB2
      generation, and the bleeding time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522347
TI  - Alignment and sensitive detection of DNA by a moving interface.
AB  - In a process called "molecular combining," DNA molecules attached at one end to a
      solid surface were extended and aligned by a receding air-water interface and
      left to dry on the surface. Molecular combing was observed to extend the length
      of the bacteriophage lambda DNA molecule to 21.5 +/- 0.5 micrometers (unextended
      length, 16.2 micrometers). With the combing process, it was possible to (i)
      extend a chromosomal Escherichia coli DNA fragment (10(6) base pairs) and (ii)
      detect a minute quantity of DNA (10(3) molecules). These results open the way for
      a faster physical mapping of the genome and for the detection of small quantities
      of target DNA from a population of molecules.

PMID- 7522356
TI  - Prevention of experimental venous thrombosis in rabbits with low molecular weight
      heparin, dextran and their combinations, administered before or during induction
      of venous endothelial trauma.
AB  - An in vivo experimental venous thrombosis model based on endothelial damage and
      flow reduction was used to investigate the effect of low molecular weight heparin
      (LMWH) alone and in combination with dextran and the effect of surgical and
      endothelial trauma on thrombus formation, formation of occlusive thrombi and
      thrombus weights. Five groups with 15 rabbits in each were studied. Two groups
      received dalteparin (50 anti-Xa IU/kg i.v.) before surgical trauma or after,
      during the endothelial trauma and two groups received dalteparin (50 anti-Xa
      IU/kg i.v.) with dextran 70 (1 g/kg i.v.) before surgical trauma or after, during
      the endothelial trauma. Compared to a control group (saline) all treatment
      regimes reduced significantly the frequency of thrombosis and occlusive thrombi
      as well as thrombus weights. No significant difference was observed between the
      identical treatment groups when the substances were introduced before respective
      after surgical trauma. It is concluded, from the present study that
      thromboprophylaxis with LMWH in this particular in vivo model, given before or
      after surgical trauma is equally effective. Dextran has a certain augmenting
      thromboprophylactic effect when added to LMWH in this model.

PMID- 7522357
TI  - Prevention of graft-versus-host disease in DLA-haplotype mismatched dogs and
      hemopoietic engraftment of CD6-depleted marrow with and without cG-CSF treatment
      after transplantation.
AB  - Prevention of graft-versus-host disease by depletion of CD6-positive T cells was
      studied in the dog. Donors were DLA-homozygous, recipients DLA-heterozygous with
      one DLA haplotype identical to the donor. Seven control dogs received untreated
      marrow and died of GvHD after full hemopoietic recovery within 28 days of
      transplantation. For prevention of GvHD, immunomagnetic separation of T cells
      with a monoclonal antibody against human CD6 that crossreacted with canine T
      cells was evaluated. Depletion of CD6-positive cells depleted CD4-positive cells
      completely, but only part of CD8-positive cells and DR-positive cells. CD6
      depleted marrow exhibited strong nonspecific "natural" suppression of the
      generation of cytotoxic T cells in vitro. Eleven dogs received CD6-depleted
      marrow. Only 1 dog developed GvHD and died. Sustained engraftment was seen in 8
      dogs. Hemopoietic recovery was delayed and slower after transplantation of CD6
      depleted marrow than after transplantation of untreated marrow. Four of these
      dogs were treated with G-CSF, and this accelerated the recovery of leukocytes,
      but did not prevent rejection. Chimerism was mixed in 7 of 10 evaluable dogs and
      1 dog recovered its own hemopoiesis 2 years after transplantation. CD6 depletion
      prevents GvHD across a DLA-haplotype difference, but rejection and mixed
      chimerism may occur. Treatment with G-CSF accelerates leukocyte recovery, but
      cannot prevent rejection.

PMID- 7522359
TI  - Localization of alpha-fetoprotein during the formation of the neural tube and
      somites in chick embryo.
AB  - Very little is known about the biological role of alpha-fetoprotein (AFP) in
      normal development. This study was undertaken to look for AFP-positive tissues
      involved in active morphogenetic and histogenetic events. Using a polyclonal
      antibody specific for AFP and the immunoperoxidase technique, we have studied the
      AFP localization during the formation of the neural tube and somites in chick
      embryo. Immunostaining of early whole embryos, cephalic fold stage, shows a
      strong immunoreaction for AFP in the cephalic and neural folds. In a more
      advanced stage of the development (6-somite stage), the AFP expression has
      followed the caudal direction of the neural fold forming process. Immunostaining
      of 6- and 9-somite embryo sections shows an increase of AFP expression from the
      most undifferentiated (the neural fold), to the most differentiated (the neural
      tube). AFP does not label the non-segmented paraxial mesoderm, from which the
      somite is derived. Instead, when the paraxial mesoderm is segmented and has
      formed a somite, AFP positive cells are detected in the somite. The morphological
      differentiation of somite is joined to one biochemical differentiation, since the
      myotome and sclerotome cells are AFP positive while the dermatome cells are AFP
      negative. The sclerotome cells become AFP negative when they surround the
      notochord to form the vertebral body. The results presented here strongly suggest
      a close association of AFP with cell proliferation and differentiation.

PMID- 7522360
TI  - Isolation of nucleic acids from the sea anemone Condylactis gigantea (Cnidaria:
      Anthozoa).
AB  - Standard procedures for isolating nucleic acids from specialized tissues such as
      the mucus-containing tissues found in many marine organisms are, in many cases,
      not effective, resulting in isolates contaminated with polysaccharides that
      encumber subsequent analysis. A method is described for isolating nucleic acids
      from the sea anemone Condylactis gigantea (Cnidaria: Anthozoa) using the compound
      hexadecyltrimethyl ammonium bromide (CTAB). This substance has historically been
      effective in producing digestible chromosomal DNA from a variety of
      polysaccharide-enriched sources. In the presence of CTAB, DNA can be isolated and
      extracted from Condylactis gigantea and is suitable for digestion with
      restriction endonucleases. With a minor modification, RNA can also be extracted
      and used to obtain mRNA. The technique is useful for Cnidarian tissues and may be
      appropriate for a variety of other marine invertebrates and algae.

PMID- 7522358
TI  - Rat monoclonal antibodies against three different epitopes of the canine Thy-1
      and their depletion capacity in vivo.

PMID- 7522362
TI  - Platelet bacterial contamination and the use of a chemiluminescence-linked
      universal bacterial ribosomal RNA gene probe.
AB  - BACKGROUND: Currently, the maximum outdate for platelets is 5 days, because of
      the increasing chance of bacterial growth over time. Various methods for rapid
      detection of bacterial contamination of blood components have been described,
      with mixed results and no general acceptance. A recently described, molecular
      biologic approach for the detection of bacterial contamination involves a
      chemiluminescence-linked universal DNA bacterial probe to a highly conserved
      bacterial region of ribosomal RNA (rRNA). STUDY DESIGN AND METHODS: A multicenter
      trial of a chemiluminescence-linked universal bacterial rRNA probe for the
      detection of bacterial contamination in platelet concentrates is described. At
      each of five sites, platelet concentrates (no older than 1 day from date of
      phlebotomy) were inoculated in triplicate with isolates of four bacterial species
      (Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus epidermidis, and
      Staphylococcus aureus) to a final concentration of 10 to 50 colony-forming units
      (CFUs) per mL and in triplicate to a final concentration of 1000 CFUs per mL. At
      one site, an additional 6 platelet concentrates were inoculated with sterile
      saline to serve as controls. Inoculated units were then subjected periodically to
      quantitative cultures and probe analyses. A total of 126 platelet concentrates
      were studied over a period of 7 days (120 inoculated with bacteria and 6 with
      sterile saline). RESULTS: This assay was, in some cases, able to detect S. aureus
      bacterial contamination in the range of 100 to 1000 CFUs per mL; the majority of
      samples (B. cereus, P. aeruginosa, S. aureus, and S. epidermidis) with
      contamination exceeding 10(4) CFUs per mL; and all samples with contamination of
      2.1 x 10(5) CFUs per mL or greater. Increasing the sample size from the
      recommended 0.4 mL to 1.0 mL resulted in an unacceptable loss of specificity
      (83.3%). CONCLUSION: The routine use of this assay would be expected to result in
      a decreased risk of septic platelet transfusion reactions and could lead to a
      lengthening of the current 5 day storage period for platelets. Further, the
      pooling of random-donor platelet concentrates before storage instead of
      immediately before transfusion may be possible if this rRNA probe is employed to
      detect bacteria in the pool.

PMID- 7522361
TI  - Localization of increased collagen in ferret lung tissue after chronic exposure
      to nitrogen dioxide.
AB  - Chronic exposure of experimental animals to moderate levels of nitrogen dioxide
      (NO2) leads to increased collagen deposition in the lung parenchyma. To localize
      this increased collagen, lung sections from ferrets exposed to 0.5 or 10 ppm of
      NO2 4 h daily for 8 or 15 weeks were stained with Sirius red under conditions in
      which the stain is specific for collagen. Stained areas of respiratory
      bronchiolar submucosa were compared between NO2-exposed and air-exposed control
      animals using computer-aided image analysis. The stained areas, relative to the
      total respiratory epithelium, were increased in the sections from NO2-exposed
      ferrets as compared to air-exposed controls after 8 or 15 weeks. Removal from
      exposure after 8 weeks and allowing a 7-week recovery did not result in a
      decrease in stained areas. In the 10 ppm group, but not in the 0.5 ppm group, the
      increase was statistically significant. Measurement of total collagen in lung
      tissue by chemical means showed no differences among the various treatment
      groups. This study showed that increases in collagen deposition can be readily
      localized in order to identify the site(s) of potentially adverse effects of air
      pollutants. It is suggested that the use of Sirius red staining may offer a
      sensitive method for detection of early fibrotic changes in the lung.

PMID- 7522363
TI  - Living related liver transplantation across ABO blood groups.
AB  - We performed 13 pediatric liver transplants from ABO-incompatible living related
      maternal or paternal donors using a combination of preoperative removal of
      isohemagglutinin and postoperative immunosuppressive therapy with FK506 and
      prophylactic OKT3. Tissue near-infrared spectroscopy was applied to evaluate
      hemodynamics using the hemoglobin of red cells in the sinusoids as an index. The
      data obtained indicated that the preoperative removal of isohemagglutinin
      prevented hyperacute humoral rejection with hemorrhagic infiltration in the
      sinusoids in 10 successful cases. The incidence of acute rejection was not
      significantly different among ABO-identical, -compatible, and -incompatible
      groups. The estimated 1-year survival rate of the ABO-incompatible group was 77%.

PMID- 7522367
TI  - A simple ligation step improves the efficiency of T-overhang vectors.

PMID- 7522365
TI  - Nitric oxide generation. A predictive parameter of acute allograft rejection.
AB  - The L-arginine:nitric oxide (NO) biosynthetic pathway has been proposed as an
      important mediator in host defense mechanisms and may therefore play a role in
      the acute allograft response. We have studied NO generation in liver allograft
      rejection and determined its value in immunological monitoring. Stable end
      products of this pathway have been determined serially in 50 primary liver
      recipients and compared with 2 known mediators and markers of acute allograft
      rejection (IL-2R positive lymphocytes and circulating TNF alpha). Plasma
      concentrations of acid-labile nitrosocompounds (NOx), which increased during
      acute allograft rejection (P < 0.0001), correlated with rejection severity and
      were reduced after administration of supplemental high dose glucocorticoids.
      Concentrations were significantly lower in nonrejection graft complications but
      were elevated during episodes of sepsis. Correlations between plasma NOx levels
      and circulating TNF-alpha (r = 0.451, P < 0.001) and IL-2R-positive lymphocytes
      in peripheral blood (r = 0.781, P < 0.001) were demonstrated. In a logistic
      analysis of these variables, plasma NOx was the most predictive parameter of an
      episode of acute cellular rejection. Nitric oxide generation in FK506-treated
      patients was lower compared with patients receiving a CsA-based immunosuppression
      regimen and was associated with a reduced frequency of acute rejection in the
      FK506 group. These data are consistent with a role for NO in the cellular
      alloantigen immune response and indicate that monitoring of plasma levels of NOx
      may be useful in the detection of acute allograft rejection.

PMID- 7522366
TI  - Anti-CD3 treatment facilitates engraftment of full H-2-disparate donor bone
      marrow cells and subsequent skin allograft tolerance.
AB  - The aim of the present study was to induce engraftment of full H-2-disparate
      donor bone marrow cells and the development of subsequent transplantation
      tolerance. To this end, recipient H-2b mice were treated with anti-CD3 and on the
      same day received 6 Gy whole body irradiation as well as donor bone marrow cells
      (H-2d). Anti-CD3 treatment was chosen because it results in suppression of T cell
      function and in the release of CSF associated with enhancement of donor bone
      marrow engraftment. Stable, long-term chimerism measured in peripheral blood and
      mesenteric lymph nodes was obtained using this preparative regimen. In contrast,
      the use of anti-CD3 F(ab')2 fragments failed to induce donor bone marrow cell
      engraftment, suggesting indeed an important role of anti-CD3-mediated growth
      factor production in marrow engraftment. To overcome the side effects of anti-CD3
      treatment (cytokine release syndrome), anti-CD4 was given 1 day before the
      treatment protocol. Omission of anti-CD3 resulted in failure of donor bone marrow
      engraftment, indicating the essential role of anti-CD3 treatment in marrow
      engraftment. Skin transplantation performed 2 and 6 months after this well
      tolerated conditioning regimen showed indefinite survival of first and second
      grafts, respectively. In addition, specific CTL nonresponsiveness developed,
      demonstrating the presence of classical transplantation tolerance across a full H
      2 barrier.

PMID- 7522364
TI  - Helper T lymphocyte unresponsiveness to cardiac allografts following transient
      depletion of CD4-positive cells. Implications for cellular and humoral responses.
AB  - Initial treatment of heterotopic cardiac transplant recipients with anti-CD4 mAb
      promotes long-term (> 60 days) allograft survival. We have used modified limiting
      dilution analysis to quantitate donor alloantigen-reactive helper T lymphocytes
      (HTL) and CTL in mice bearing long-term cardiac allografts. Despite repopulation
      of lymphoid tissues with CD4+ T cells, donor alloantigen-reactive IL-2 producing
      and IL-4-producing HTL were rare or not detectable in lymphoid tissues or in the
      graft. While donor-reactive precursor CTL were present in lymphoid tissues,
      modified limiting dilution analysis revealed that stimulated ("antigen
      conditioned") CTL were not detectable, and few CTL were present in the graft. In
      addition, antibodies reactive with donor alloantigens were not detectable in the
      sera of mice bearing long-term cardiac allografts. To determine whether
      additional in vivo stimulation with donor alloantigens would elicit an immune
      response, sponge allografts were implanted into mice bearing long-term cardiac
      allografts. Previous reports from this laboratory have demonstrated that T cell
      infiltration of sponge allografts is dependent upon antigen-driven cytokine
      production. While third-party sponge allografts were readily infiltrated by third
      party-reactive HTL and CTL, sponge allografts of the same strain as the cardiac
      allograft were not infiltrated by T cells. However, donor strain sponge
      allografts induced an IgM (but not IgG) alloantibody response. These data
      indicate that IgM alloantibody could be induced in the absence of a cellular
      response to the sponge allograft. Kinetic studies revealed that a transient IgM
      (but not IgG) response was induced by the initial cardiac transplantation in the
      absence of CD4+ cells. These IgM alloantibodies disappeared by day 21 despite the
      persistence of the allograft. These observations indicate that transient
      depletion of CD4+ T cells induces allograft-specific T cell tolerance, but does
      not eliminate the ability to mount an allograft-specific IgM response. To our
      knowledge, this is the first report of a transient humoral response to
      alloantigens that occurs in the absence of CD4+ T cells, and can be reinduced in
      "tolerant" animals that fail to mount a cellular immune response. Potential
      mechanisms involved in the development and maintenance of anti-CD4 mAb-induced
      tolerance are discussed.

PMID- 7522368
TI  - Early immunodiagnosis of caprine fasciolosis using the specific f2 antigen in a
      passive hemagglutination test.
AB  - An improved hemagglutination (HA) test using the purified specific f2 antigen of
      Fasciola hepatica has been evaluated with respect to its potential use in the
      diagnosis of caprine fasciolosis. Following experimental infection of 1-year-old
      goats with a single heavy infection of 300 metacercariae, f2-specific antibodies
      were detected 2-3 weeks after infection and increased steadily to reach a maximum
      titer 9 weeks after infection, after which the antibody level declined. In
      animals receiving multiple infections of a lower dose of 50 metacercariae given
      at weekly intervals for 6 weeks, f2-specific antibodies were detected 3 weeks
      after infection and increased to reach a plateau 11 weeks after infection which
      was maintained until the end of the experiment (15 weeks after infection).
      Depending on animals and groups, eggs appeared in the feces between 7 and 9 weeks
      after infection. The HA test may provide valuable information about the early
      detection of caprine fasciolosis, particularly during the prepatent period.

PMID- 7522369
TI  - Mapping the subgroup epitopes of rotavirus protein VP6.
AB  - VP6, the most abundant protein of rotaviruses, contains epitopes that allow the
      classification of these viruses into four subgroups (SG), depending on the
      presence or absence of two epitopes called I and II. The subgroup-specific
      epitopes are conformational and appear to be present on trimeric but not
      monomeric VP6. We have identified on VP6 some of the amino acids that determine
      the reactivity of the subgroup-specific mAbs 255/60 and 631/9. A single amino
      acid mutation at positions 172 (Met to Ala) or 305 (Asn to Ala) was sufficient to
      change the subgroup specificity of the human rotavirus Wa VP6 protein from SGII
      to SGI/II, since either of these mutations allowed the protein to be recognized
      by the SGI mAb 255/60, while retaining its capacity to interact with the SGII mAb
      631/9. In the case of the SGII epitope, the mutation of two contiguous amino
      acids (Ala305 Asn306 to Asn305 Ala306) in the porcine rotavirus YM VP6 protein
      (SGI) enabled the protein to be efficiently recognized by the SGII mAb 631/9,
      while causing the YM VP6 protein to lose its capacity to interact with mAb
      255/60. These results suggest that both subgroup Abs interact with an antigenic
      domain in VP6 that is composed of at least two regions of the protein that,
      although distant in the linear sequence, might be in close proximity in the
      structured VP6 trimer.

PMID- 7522372
TI  - Mapping of antigenic domains in poliovirus VP1 involved in structural
      rearrangements during virus morphogenesis and antigenic alterations of the
      virion.
AB  - Monoclonal antibodies (mAbs) directed against linear epitopes of the structural
      polypeptide VP1 of poliovirus type 1, Mahoney (PV1M), were used as sensitive
      tools to evaluate the accessibility of certain amino acid residues, both during
      virus morphogenesis and after conformational transitions of the capsid resulting
      from heat treatment (H- or 80S particles) and cell-receptor interaction (A- or
      135S particles). Antibody binding sites were mapped by immunoblotting of VP1
      fragments after procaryotic expression and by introduction of nested sets of
      deletions into recombinant VP1. The binding sites clustered at the amino- and
      carboxy-termini of the polypeptide, respectively. In 14S particles the amino
      terminal sites were accessible for our mAbs, most likely from the inner surface
      of the particle. The carboxy-terminal sites became inaccessible during formation
      of pentamers from protomers. As shown by differential reaction of the mAbs, the
      amino-terminus of VP1 becomes externalized up to residues 41-55, whereas residues
      56-67 remain buried during transition to both 80S and 135S particles. Carboxy
      terminal residues 280-286 also become accessible to antibody binding on the
      surface of the altered particles. Since these residues are part of the canyon
      cleft of VP1, a structural rearrangement indicated by these mAbs is apparently
      associated with the loss of binding ability of 135S particles to the cellular
      receptor, which could explain the loss of infectivity of these particles.

PMID- 7522371
TI  - Purification, properties, and subcellular localization of foxtail mosaic
      potexvirus 26-kDa protein.
AB  - The open reading frame 2 (ORF2) of the potexviral genome encodes a 24- to 26-kDa
      protein which is part of the "triple gene block," a group of overlapping ORFs
      also present in the genomes of the carla-, hordei-, and furoviruses. The product
      of these ORFs is believed to play a role in the cell-to-cell movement of the
      viruses in host plants. The amino acid sequences of the homologous ORF2 products
      encoded by these related viruses suggest that they specify NTP binding and
      possibly helicase activities. We have used an Escherichia coli expression system
      to produce significant amounts of the 26-kDa protein (p26) encoded by foxtail
      mosaic potexvirus ORF2. p28 was purified to near homogeneity by conventional
      purification methods and some of its biochemical properties were determined. We
      present evidence that p26 is an ATP, CTP, and RNA binding protein with apparent
      ATPase activity. Western blot analysis of infected plant extracts using a
      polyclonal antiserum produced against p26 indicates that it is a relatively
      stable protein maintained at high levels for at least 6 days following its peak
      level of expression. Moreover, it is found predominantly in the soluble fraction
      of infected tissues. An immunocytochemical analysis of infected Chenopodium
      quinoa leaves reveals that p26 is exclusively associated with cytoplasmic
      inclusions in proximity to but distinct from aggregates of viral particles.

PMID- 7522373
TI  - Presentation of neutralizing epitopes by engineered rotavirus VP7's expressed by
      recombinant vaccinia viruses.
AB  - Previous studies showed that a calcium-dependent neutralization domain forms on
      the rotavirus glycoprotein VP7 during assembly into particles. Here, we
      demonstrate that expressed, recombinant VP7 is capable of forming this
      neutralization domain in the absence of other rotavirus proteins, but that the
      domain is unstable. High calcium environments, incorporation into particles, and
      binding of neutralizing antibodies stabilize the neutralization domain on
      expressed VP7. A chimeric, cell surface-anchored molecule, VP7sc, has an enhanced
      ability to react with neutralizing antibodies. This may explain why immunization
      of mice with expressed native VP7 has had limited success while immunization with
      VP7sc efficiently induced neutralizing antibodies and passively protected pups
      from diarrhea. A model of VP7 folding consistent with these results is presented.

PMID- 7522374
TI  - The gene expression of human foamy virus does not require a post-transcriptional
      transactivator.
AB  - Human foamy virus (HFV) comprises a complex genomic organization of gag, pol,
      env, and several nonstructural genes such as bel1, bel2, bel3, bet, beo, and bes
      located between env and 3' LTR. Among these viral nonstructural genes, bel1
      appears to encode an essential transactivator of LTR-directed gene expression. To
      investigate the roles of the other nonstructural proteins for the viral
      replication, a series of proviral mutants were generated and tested for their in
      vitro replication. The mutations in the other than bel1 open reading frame did
      not show any significant effect on viral replication. The bel1 protein is the
      only essential transactivator for the LTR-directed transcription. To determine
      whether HFV has an essential post-transcriptional transactivator like the rev
      protein of human immunodeficiency virus type 1, or the rex protein of human T
      cell leukemia virus type 1, we investigated the bel1-independent expression of
      the HFV gag structural gene under the control of the heterologous simian virus 40
      promoter. We demonstrated that the expression of the HFV gag structural gene does
      not require an essential post-transcriptional transactivator. Thus, it appears
      that the regulation of HFV gene expression is distinct from that of other human
      retroviruses.

PMID- 7522370
TI  - Glycosylation within an antigenic site on the HN glycoprotein of Newcastle
      disease virus interferes with its role in the promotion of membrane fusion.
AB  - The binding of monoclonal antibodies to antigenic site 3 on the hemagglutinin
      neuraminidase (HN) glycoprotein of Newcastle disease virus neutralizes viral
      infectivity and prevents syncytium formation by a mechanism other than the
      prevention of viral attachment. The virus can escape neutralization by these
      antibodies by the addition of an N-glycan at a site introduced by a D287N
      mutation in HN. The variant has significantly reduced ability to induce fusion
      from within, the mode of fusion promoted by the viral glycoproteins deposited on
      the cell surface late in infection. Conversely, and unlike the parent virus, the
      variant has acquired the ability to promote fusion from without, the mode of
      fusion directly mediated by input virions at high multiplicity. This finding is
      consistent with different roles for the HN protein in virion-cell and cell-cell
      fusion. D287N-mutated HN with its additional N-glycan shows a markedly reduced
      ability, compared to wild-type HN, to complement the viral fusion protein in the
      promotion of fusion in a BHK cell transient expression system. This confirms that
      the addition of an N-glycan in HN antigenic site 3 and the deficiency in
      syncytium formation are causally related. Moreover, no alteration in cell surface
      expression, hemadsorption, or neuraminidase activity was detected in the mutated
      protein. This monoclonal antibody-selected mutation suggests that a fusion
      related function, secondary to receptor recognition, may be defined by the
      globular head of the HN spike. However, D287C or D287S-mutated HN is as effective
      as the wild-type protein in the promotion of fusion in the coexpression system.
      This suggests that the diminished fusogenicity of the D287N-mutated protein is
      probably due to a more global effect of glycosylation in site 3 rather than an
      alteration at the amino acid level.

PMID- 7522375
TI  - Proteolytic cleavage at the Gag-Pol junction in avian leukosis virus: differences
      in vitro and in vivo.
AB  - In avian leukosis virus, processing by the viral protease (PR) appears to
      activate reverse transcriptase (RT), since PR-defective virions have extremely
      feeble reverse transcriptase activity. We showed previously that when such
      detergent-treated virions are digested in vitro with PR, the Gag precursor is
      completely and properly matured, but the Gag-Pol precursor is not. In particular,
      the junction between Gag and Pol, i.e., between the PR and RT domains in Gag-Pol,
      remains refractory to cleavage, and reverse transcriptase is hardly activated. We
      have now investigated processing between Gag and Pol in greater detail, both in
      vitro and in vivo. In vivo, three mutations designed to destroy or alter the
      cleavage site at the N-terminus of RT failed to abrogate processing, suggesting
      that nearby cryptic cleavage sites can be used by PR, and thus that in virions
      this portion of Gag-Pol is in an extended conformation. By contrast, resistance
      to cleavage was observed in vitro in a series of N- and C-terminally truncated
      Gag-Pol substrates, produced by in vitro translation or in the baculovirus-insect
      cell system. This resistance was maintained even in short polypeptides, implying
      that the inability to be processed in vitro is a consequence of local
      conformation. In the previously described Gag mutant cs22, which is unable to
      undergo full activation of PR, we found that in vivo in quail cells the only
      cleavages made in the Gag-Pol polypeptide are at the NC-PR and the PR-RT
      junctions, suggesting that in wild-type avian leukosis virus, processing of Gag
      Pol begins by cleavage immediately upstream and downstream of the PR domain.
      Taken together, these results suggest a model in which in immature virions the
      segment of polypeptide between PR and RT is held in an extended but inherently
      unstable conformation, and that in vivo the first cleavage in Gag-Pol must occur
      in this region. In the absence of virion structure this segment of polypeptide
      collapses into its most stable conformation, preventing cleavage. Based on amino
      acid sequence, we predict that this portion of Gag-Pol adopts a coiled coil
      conformation reminiscent of a leucine zipper.

PMID- 7522376
TI  - Expression of the glycoprotein H of murine cytomegalovirus and identification of
      an N-terminal antibody-binding region.
AB  - A series of overlapping fragments spanning the entire coding sequence of the gH
      gene of murine cytomegalovirus (MCMV) were expressed in Escherichia coli as
      fusion proteins with glutathione S-transferase (GST) using the pGEX expression
      system. A region of antibody-binding was mapped to the NH2-terminus of
      glycoprotein H (gH) between amino acid residues 26 and 90 on the basis of the
      reactivity of GST-gH fusion proteins with polyclonal antibodies to MCMV in
      Western blot analysis. Antibodies to gH were generated in mice immunized with the
      GST-gH fusion protein SK and shown to react with an 87-kDa polypeptide present in
      virion particles which was conserved in MCMV isolates obtained from diverse
      locations. They also recognized the gH protein in MCMV-infected cells, as well as
      gH expressed in Chinese Hamster Ovary cells. The antibodies to gH had a
      significant ELISA titer but no neutralizing activity in vitro. The antibody
      response to the GST-gH fusion protein did not modify the level of MCMV
      replication in the spleens of mice.

PMID- 7522377
TI  - Topology of bovine rotavirus (RF strain) VP6 epitopes by real-time biospecific
      interaction analysis.
AB  - An automated biosensor system designed for measuring molecular interactions in
      real-time (BIAcore) was used to characterize monoclonal antibodies (Mabs) raised
      against the inner capsid protein (VP6) of the bovine rotavirus (RF strain). Six
      Mabs, all reactive in Western blot and in indirect immunofluorescence assays,
      were mapped, using purified recombinant VP6. These Mabs were delineated into
      several groups of antibodies. Interactions of selected monoclonal antibodies with
      purified viral particles were studied by the BIAcore methodology. We showed that
      some Mabs did not react with single-shelled particles. Conversely, several Mabs
      reacted with single-shelled particles and one antibody reacted with both single
      shelled and double-shelled particles. The latter Mab seemed to interact with VP6
      through the holes of the outer capsid and its interaction with the double-shelled
      particles induced a significant decapsidation. These results allowed a better
      characterization of the epitopes of VP6. The localization of the epitopes in the
      viral particle is discussed in comparison with a pepscan study that determined
      the reactivity of Mabs with nested heptapeptides derived from the whole VP6
      molecule.

PMID- 7522379
TI  - [Degree of substitution and volume expanding effect of various medium molecular
      weight hydroxyethyl starch solutions].
AB  - Hydroxyethylstarch (HES) is today one of the most frequently used artificial
      plasma substitutes in prehospital, as well as in clinical settings. However,
      there are no studies comparing the volume effect of different HES solutions. The
      goals of the present study therefore were to compare the volume effect of three
      HES solutions, which are similar with regard to mean molecular weight but
      different in concentration and degree of substitution. The obtained results
      enable guidelines for fluid resuscitation in hypovolemia to be laid down. In 30
      patients fulfilling the ASA physical status classification I and II 500 ml of
      either 10% HES 200/0.5, 6% HES 200/0.5 or 6% HES 200/0.6-0.66 were infused within
      30 min. The effect of each solution was evaluated using the mechanical oscillator
      technique (MOT). This technique measures precisely density changes of blood and
      plasma and allows-using standard formulae-calculation of blood and plasma volume
      changes. All 3 HES solutions showed similar effects in increasing plasma volume.
      Immediately after the end of infusion plasma volume was increased by about 800 ml
      with 10% HES and by about 650 ml with 6% HES 200/0.5. The volume expanding effect
      of 6% HES 200/0.6-0.66 amounted to 700 ml. The volume expanding effect of all
      starches decreased only slightly during the following two hours; an interesting
      detail observed was a second volume effect of HES (about 20% of the volume
      infused). We conclude that for the correlation of fluid deficits due to trauma,
      hemorrhage and shock HES solutions seem to be most effective artificial plasma
      substitutes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522378
TI  - [The biological activity of saparal in an influenzal infection].
AB  - The antiviral and interferon-inducing activity of saparal, an adaptogen of plant
      origin, was studied. Tests in experimental mice demonstrated the interferon
      inducing activity of saparal providing its antiviral effect. An optimal scheme of
      saparal administration was developed. The preparation had no direct inhibitory
      effect on influenza virus replication. The application of saparal for prophylaxis
      among workers resulted in a 2-fold or greater decrease of influenza and other ARD
      morbidity and in an increase of endogenous serum interferon level in 67-75% of
      the persons examined.

PMID- 7522381
TI  - Use of oral enoximone in pharmacologic bridging to cardiac transplantation.

PMID- 7522380
TI  - [Interferons in cancer treatment: yesterday, today and tomorrow].

PMID- 7522384
TI  - Ki-S1 and proliferating cell nuclear antigen expression of bone marrow
      macrophages. Immunohistochemical and morphometric study including reactive
      (inflammatory) myelitis, secondary aplastic anemia, AIDS, myelodysplastic
      syndromes and primary (idiopathic) osteomyelofibrosis.
AB  - There is general agreement on the fact that bone marrow macrophages present a non
      proliferating cell population. Using a sequential double-immunostaining
      technique, a morphometric analysis was performed on routinely processed bone
      marrow biopsies derived from 70 patients. The purpose of this study was, firstly,
      to determine the frequency of bone marrow macrophages in a variety of lesions
      and, secondly, to elucidate whether there is any proliferative activity
      detectable by immunohistochemical markers. Bone marrow pathology included
      reactive myelitis (RM), secondary aplastic anaemia (AP), AIDS-related myelopathy,
      primary (idiopathic) osteomyelofibrosis (OMF) and myelodysplastic syndromes
      (MDS). The monoclonal antibody PG-M1 which recognizes a formalin-resistant
      epitope on macrophages and PC10 raised against proliferating cell nuclear antigen
      (PCNA) were employed. For comparison with the PCNA-labelling index, the newly
      developed monoclonal antibody Ki-S1, which is associated with cell proliferation,
      was applied. In comparison with normal bone marrow, morphometric evaluation
      revealed a significant increase in macrophages in MDS, OMF, RM and especially in
      HIV-infected patients. Moreover, a positive immunostaining of single macrophages
      with PC10 was noted very infrequently. This rather inconspicuous PCNA labelling
      increased in AIDS. By contrast, Ki-S1 expression was found in none of the other
      pathologies studied. The prevalence of the macrophage population in certain
      disorders may have a multifactorial origin, such as inflammatory changes like
      intercurrent infections in AIDS and enhanced cell turnover in MDS as well as
      involvement of the complex pathomechanisms generating bone marrow fibrosis. In
      keeping with previous studies, the insignificant PCNA expression of macrophages
      should not be related to cell proliferation, but to unscheduled DNA strand repair
      which may be generated in the course of viral infection in AIDS.

PMID- 7522383
TI  - Immunogenicity of recombinant influenza virus haemagglutinin carrying peptides
      from the envelope protein of human immunodeficiency virus type 1.
AB  - Haemagglutinin (HA), the major surface glycoprotein of influenza virus, is a
      potent immunogen against which viral neutralizing antibodies are directed.
      Studies of the three-dimensional structure of HA have identified major antigenic
      sites on the molecule. We have exploited HA as a carrier for small antigenic
      regions (epitopes) of the HIV-1 envelope (env) glycoprotein. Using recombinant
      DNA techniques, the epitopes were inserted in-frame into a known antigenic site
      of HA to produce HA-epitope chimeras. Guinea-pigs and mice immunized with these
      chimeras in combination with adjuvant generated significant immune responses
      against the carrier HA and also produced epitope-specific antibodies that
      recognized the native whole HIV-1 env. One of the chimeras which contained a V3
      loop sequence of HIV-1 env elicited neutralizing antibodies against the
      homologous strain of HIV-1. The antibodies against HA and the inserted epitopes
      remained at high levels for up to 72 weeks. Remarkably, these responses were
      generated with low doses of immunogens containing only nanogram quantities of the
      inserted epitopes. These results suggest the utility of HA as a carrier to allow
      selective antibody induction against foreign epitopes, and offer a new approach
      for vaccine development as well as for the production of monospecific antibodies
      useful in diagnostics and research.

PMID- 7522382
TI  - Hypervariable epitope constructs as a means of accounting for epitope
      variability.
AB  - Epitope variability is one of the greatest obstacles to development of synthetic
      peptide vaccines. Based on a recently described hypervariable epitope (aa 414
      434) on the envelope glycoprotein (gp130) to simian immunodeficiency virus
      (SIVmac142), we have developed a novel approach to account for epitope
      variability. We have prepared, in a single synthesis, a cocktail of peptides,
      designated a hypervariable epitope construct (HEC), which collectively represent
      all the in vivo variability seen in an epitope. The HEC represents permutations
      of amino acid substitutions found in the epitope and has been able to induce
      antibodies with enhanced binding to native SIV and broad immunoreactivity to
      related epitope analogues.

PMID- 7522385
TI  - Primary T cell non-Hodgkin's lymphoma of the central nervous system. Case report
      and review of the literature.
AB  - A 42-year-old man developed primary non-Hodgkin's lymphoma of the central nervous
      system (CNS). Immunohistochemical examination suggested that tumor cells were
      derived from T cells. Primary T cell non-Hodgkin's lymphoma of the CNS is a rare
      tumor, with only 12 well-documented cases in the literature. The clinical
      features of these 12 cases were similar to those of other CNS lymphomas, and the
      effect of treatment and prognosis were usually worse than those of extranodal
      lymphoma. Our patient, who was treated with partial tumor resection and whole
      brain irradiation with a boost to the primary site and 5 courses of CHOP therapy
      (cyclophosphamide, doxorubicin, vincristine, prednisolone), is still alive and in
      remission 38 months after diagnosis.

PMID- 7522386
TI  - A sequence of cytoskeleton changes related to the formation of neurofibrillary
      tangles and neuropil threads.
AB  - Frontal sections of the temporal lobe including the transentorhinal/entorhinal
      region, amygdala, and/or hippocampus from human adult brains are studied for
      cytoskeleton changes using immunostaining with the antibodies AT8 and Alz-50 and
      selective silver impregnation methods for neurofibrillary changes of the
      Alzheimer type. For the purpose of correlation, the two methods are carried out
      one after the other on the same section. Layer pre-alpha in the
      transentorhinal/entorhinal region harbours nerve cells which are among the first
      nerve cells in the entire brain to show the development of neurofibrillary
      changes. This presents the opportunity for study of both early events in the
      destruction of the cytoskeleton in individual neurons, and to relate changes
      which occur in the neuronal processes in the absence of alterations in their
      immediate surroundings to those happening in the soma. Immunoreactions with the
      AT8 antibody in particular reveal a clear sequence of changes in the neuronal
      cytoskeleton. Group 1 neurons present initial cytoskeleton changes in that the
      soma, dendrites, and axon are completely marked by granular AT8 immunoreactive
      material. These neurons appear quite normal and turn out to be devoid of
      argyrophilic material when observed in silver-stained sections. Group 2 neurons
      show changes in the cellular processes. The terminal tuft of the apical dendrite
      is replaced by tortuous varicose fibres and coarse granules. The distal portions
      of the dendrites are curved and show appendages and thickened portions. Intensely
      homogeneously immunostained rod-like inclusions are encountered in these
      thickened portions and in the soma. A number of these rod-like inclusions are
      visible after silver staining, as well. Group 3 neurons display even more
      pronounced alterations of their distal--most dendritic portions. The intermediate
      dendritic parts lose immunoreactivity, but the soma is homogeneously
      immunostained. Silver staining reveals in most of the distal dendritic parts
      neuropil threads, and in the soma a classic neurofibrillary tangle. Group 4
      structures are marked by accumulations of coarse AT8-immunoreactive granules.
      Silver staining provides evidence that the fibrillary material has become an
      extraneuronal, "early" ghost tangle. Finally, group 5 structures present "late"
      ghost tangles in silver-stained sections but fail to demonstrate AT8
      immunoreactivity. It is suggested that the altered tau protein shown by the
      antibody AT8 represents an early cytoskeleton change which eventually leads to
      the formation of argyrophilic neurofibrillary tangles and neuropil threads.

PMID- 7522388
TI  - Immunohistochemical analysis of the distribution of MyoD1 in muscle biopsies of
      primary myopathies and neurogenic atrophy.
AB  - The expression of the myogenic determination gene MyoD1 plays a primary role in
      the commitment of primitive mesenchymal cells to a striated muscle lineage and is
      down-regulated during later stages of differentiation. To determine the potential
      role of this gene in myopathic conditions, we examined its expression by means of
      immunohistochemical analysis, using a series of muscle biopsies from 14 patients
      with a variety of primary myopathies and neurogenic disorders. Utilizing the
      avidin-biotin-complex technique, cryostat sections were stained with monoclonal
      antibody 5.8 A, which we have previously described as having a high level of
      specificity for tumors with rhabdomyoblastic differentiation. Of special interest
      was the observation in 4 of 8 cases of neurogenic atrophy of varying levels of
      cytoplasmic positivity of muscle fibers, appearing to correlate with their degree
      of atrophy, in addition to weak nuclear staining. Muscle biopsies from 2 patients
      with Duchenne's muscular dystrophy and 2 patients with autoimmune inflammatory
      myopathies demonstrated various levels of nuclear positivity in scattered foci
      that appeared to correlate with areas of regeneration. A biopsy from a single
      case of neurogenic atrophy secondary to infantile spinal muscular atrophy
      (Werdnig-Hoffmann's disease) demonstrated diffuse but relatively weak staining of
      myofiber nuclei, in contrast to sections of normal striated muscle and muscle
      biopsies from patients with unexplained myoglobinuria, which exhibited only
      minimal amounts of staining. These data are compatible with observations that
      MyoD1 expression is related to electrical activity and muscle regeneration.

PMID- 7522387
TI  - Colocalization of growth hormone (GH) and glycoprotein subunit alpha in GH
      producing pituitary adenomas in acromegalic patients.
AB  - Thirty-one consecutive cases of pituitary adenoma in acromegalic patients were
      studied by immunohistochemistry. All adenomas contained cells immunoreactive with
      the anti-alpha-subunit of gonadotropic hormones (alpha; 0.6-53% of tumor cells)
      as well as with anti-growth hormone (GH; 4-74% of tumor cells). In serial section
      study, most cells immunoreactive with anti-alpha were identical to cells
      immunoreactive with anti-GH. There was a positive correlation between the
      percentages of cells immunoreactive for alpha in GH cells [alpha (%)/GH(%)] and
      those for prolactin (PRL) in immunoreactive tumor cells (PRL(%)/[PRL(%) + GH(%)])
      in mixed GH cell-PRL cell adenomas, suggesting that the alpha-subunit may play a
      role in emergence of PRL cells.

PMID- 7522391
TI  - Developmental brain-stem pathology in sudden infant death syndrome.
AB  - The brain-stems of control and sudden infant death syndrome (SIDS) infants were
      examined developmentally with Golgi and immunohistochemical methods. The
      development of dendritic spines changed dramatically from the prenatal to
      postnatal period in the ventrolateral medulla as well as in the reticular
      formation and vagal nuclei in controls, but persisted in SIDS infants. These
      observations suggest a delay in maturation of the meduallary respiratory neurons
      and transneuronal connection between the central chemoreceptor and neural
      respiratory center in SIDS. In addition, substance P (SP)-positive nerve fibers
      were increased in the pons of SIDS infants. An increased activity in the afferent
      SP neurons in SIDS may be due to chronic hypoxia as in brain-stem gliosis, and
      may be involved in cardiorespiratory regulation.

PMID- 7522390
TI  - Development of polyclonal antibodies and evaluation of a sensitive
      radioimmunoassay for detection and measurement of synaptophysin.
AB  - Polyclonal antibodies directed towards synaptophysin were raised against a
      synthesised peptide corresponding to amino acids 246 to 260 of the human
      synaptophysin sequence. The antibodies, when applied for immunocytochemical
      staining, showed a staining pattern identical to that of the commercially
      available monoclonal antibody SY-38. A radioimmunoassay for measurements of
      synaptophysin was developed using these antibodies and the peptide as standard
      and tracer. The radioimmunoassay was used for optimising the conditions for
      purification of synaptophysin from rat brain. No synaptophysin was detected in
      blood plasma in humans, not even during an embolisation treatment of tumour
      metastases in the liver, which induced tumour cell necrosis, in a patient with
      carcinoid tumours. By radioimmunoassay, synaptophysin was detected in cell
      homogenate from the PC-12 (160 ng/mg) and LCC-18 (40 ng/mg) cell lines and in the
      cell culture media. In the LCC-18 cell line the synaptophysin immunoreactivity
      was found in the plasma membrane, and the presence of synaptophysin was confirmed
      both by radioimmunoassay measurements and by the Northern blot technique. These
      data indicate that measurements of synaptophysin using this radioimmunoassay are
      reliable and that the assay can serve as a useful tool in further explorations of
      the biological effects of synaptophysin.

PMID- 7522389
TI  - Permanent increase of immunocytochemical reactivity for gamma-aminobutyric acid
      (GABA), glutamic acid decarboxylase, mitochondrial enzymes, and glial fibrillary
      acidic protein in rat cerebral cortex damaged by early postnatal hypoxia
      ischemia.
AB  - A former study indicated that hypoxic-ischemic encephalopathy in rat sustained
      during early postnatal life may result in permanent epileptic activity in the
      baseline electroencephalogram. We, therefore, investigated whether the presumed
      higher firing frequency and metabolic activity of neurons in such hypoxia-damaged
      cortical areas would be reflected by an enhanced light microscopic
      immunoreactivity of gamma-aminobutyric acid (GABA), the two isoforms of glutamic
      acid decarboxylase (GAD67 and GAD65), the mitochondrial enzymes cytochrome c
      oxidase and ATP synthase, and/or glial fibrillary acidic, protein (GFAP). To that
      end rat pups, 12-13 days of age, were unilaterally exposed to hypoxic-ischemic
      conditions and, after a survival period of 2 and 6 1/2 months, respectively,
      killed by perfusion fixation. After dissection of the brain, coronal vibratome
      sections of animals showing cortical damage were immunostained for the presence
      of the above-mentioned antigens. Subsequent qualitative analysis revealed that
      the surroundings of cortical infarctions were unambiguously characterized by a
      disordered neural network containing numerous nerve cells, fibers and/or endings
      showing an enhanced immunoreactivity for GABA, both isoforms of glutamic acid
      decarboxylase, and cytochrome c oxidase and ATP synthase, while the astrocytes
      showed an enhanced immunoreactivity for GFAP. The diverse patterns of enhanced
      immunoreactivity suggested, furthermore, a wider low-to-high range of metabolic
      activities in both excitatory and inhibitory neurons.

PMID- 7522392
TI  - Weaning-food viscosity and energy density: their effects on ad libitum
      consumption and energy intakes in Jamaican children.
AB  - The effects of weaning-food viscosity and energy density on consumption and
      energy intake were determined in 15 non-breast-fed Jamaican children aged 7-15 mo
      under standardized conditions. We tested whether feeding thick, energy-dense
      porridge four times daily resulted in increased energy intakes and whether
      amylase treatment to reduce viscosity offered any advantage. When a traditional
      liquid, low-density porridge (2.15 kJ/g) was fed, the mean (+/- SD) daily
      consumption was 139 +/- 25 g/kg and the mean daily energy intake was 296 +/- 54
      kJ/kg. When a semisolid high-density porridge (4.09 kJ/g) was fed, consumption
      was significantly lower (98 +/- 21 g/kg) but the daily energy intake was
      significantly higher--402 +/- 85 kJ/kg (P < 0.001). Amylase treatment of the
      thick energy-dense porridge did not increase intakes further. Meal duration for
      the thick porridge (12.9 +/- 4.0 min) was significantly longer than that for the
      low-density (7.4 +/- 2.6 min) or amylase-treated (6.4 +/- 1.8 min) porridges.

PMID- 7522394
TI  - Can prostate-specific antigen levels predict bone scan evidence of metastases in
      newly diagnosed prostate cancer?
AB  - Staging in prostate cancer, as in any other cancer has significant ramifications
      in management. Currently, prostate-specific antigen (PSA) determination and the
      bone scan are two important procedures in the pretreatment staging workup of
      prostate cancer. PSA is a very useful serum tumor marker in the management of
      prostate cancer patients. We retrospectively evaluated 90 patients at the time of
      initial diagnosis of prostate cancer, all of whom had initial PSA levels
      measured, as well as bone scans obtained. In addition to the PSA level, we
      considered clinical stage and pathologic grade in the prediction of bone scan for
      metastases, at the time of initial diagnosis of prostate cancer. Negative
      predictive value for PSA values < 10 ng/ml (27 patients), clinical stage A (9
      patients) and pathologic grade 1 (19 patients) was 100%. The number of patients
      with bone scan evidence of metastasis with < 10 ng/ml and > 10 ng/ml PSA levels
      were 0% (0/27 patients) and 27% (17/63 patients) (p = .0022 [Fisher's Exact
      test]; p = .003 [chi-square test]). In patients with higher stage (p = .688),
      grade (p = .039), or PSA levels (p = .0001), the incidence of bone metastases
      increased. However, none of these three parameters can predict reliably bone scan
      evidence of metastases (i.e., positive predictive value). The negative predictive
      values did not improve when a combination of the two or three of the above
      parameters were used.

PMID- 7522393
TI  - The efficacy of recombinant human granulocyte colony-stimulating factor and
      recombinant human granulocyte macrophage colony-stimulating factor in permitting
      the administration of higher doses of cyclophosphamide in a doxorubicin
      cyclophosphamide combination. An NSABP pilot study in patients with metastatic or
      high-risk primary breast cancer. National Surgical Adjuvant Breast and Bowel
      Project.
AB  - Colony-stimulating factors (CSFs) shorten the duration of myelosuppression
      following chemotherapy and, thus, allow the administration of higher doses. This
      study evaluates the efficacy of granulocyte macrophage colony-stimulating factor
      (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in allowing
      administration of high-dose cyclophosphamide in combination with doxorubicin.
      Ninety women with metastatic, locally advanced, or high-risk (> or = 10 positive
      nodes) breast cancer and no prior anthracycline treatment were given doxorubicin
      (60 mg/m2) with progressively increased doses of cyclophosphamide (1,200 mg/m2,
      1,800 mg/m2, and 2,400 mg/m2). The first 60 patients received GM-CSF; the
      remaining 30, G-CSF. The maximum tolerated dose was not reached with 2,400 mg/m2
      of cyclophosphamide. When compared to GM-CSF, G-CSF significantly reduced the
      duration of granulocytopenia (P < .001). No differences in duration of
      thrombocytopenia were noted. The results were not sufficiently consistent to
      indicate a trend toward reduction in rates of febrile neutropenia with one CSF
      versus the other. However, patients who received G-CSF were hospitalized less
      frequently than those receiving GM-CSF. With CSFs, high-dose cyclophosphamide in
      combination with doxorubicin can be safely administered on an outpatient basis. A
      shorter duration of granulocytopenia resulted from the use of G-CSF than from GM
      CSF.

PMID- 7522396
TI  - Improvement of sickle cell anemia by iron-limited erythropoiesis.
AB  - We report the hematologic and clinical features of four adult patients (Pts.)
      with sickle cell anemia and iron-limited erythropoiesis. Two of the Pts. had
      spontaneous iron deficiency (chronic GI bleeding, low-grade hemoglobinuria). In
      the other two Pts. iron restriction was induced by periodic RBC aphereses as part
      of a pilot protocol designed to decrease intracellular HbS polymerization by MCHC
      reduction. Iron-limited erythropoiesis was defined by reduction in red cell
      indices (MCV range 60.4-67 fl) in the presence of low serum ferritin (range < 10
      20 ng/ml). In these Pts. iron restriction did not cause clinically significant
      worsening of the anemia (Hb 7.8-9.0 g/dl). In two Pts. the anemia actually
      improved. Other hematologic effects of iron restriction were: decreased MCHC,
      reticulocyte count, RDW, and dense cells. A reduced hemolytic rate was suggested
      by a lowering of serum bilirubin and LDH. In one of the Pts. the 51Cr RBC T1/2
      survival increased from 12 to 16 days. The intracellular HbS polymer fractions
      (fp) were determined at 25% O2 by Csat and with the use of the conservation of
      mass equation. The baseline fp values ranged from 0.48-0.53. After iron
      restriction they ranged from 0.33-0.48. The fp decreased even though iron-limited
      erythropoiesis also lowered the Hb F concentration in three of our Pts. In one of
      the two Pts. with induced iron depletion, hospitalization days for pain crises
      decreased from an average of 4.5 days/month (2 year baseline period) to an
      average of 0.5 days/month in the 3 year follow-up after iron depletion. The
      second patient with induced iron restriction experienced the rapid healing of a
      leg ulcer. Controlled iron restriction should be explored as a therapeutic
      strategy in selected SS patients.

PMID- 7522395
TI  - Optimal blood stem cell mobilization using 10 micrograms/kg granulocyte colony
      stimulating factor (G-CSF) alone for high-dose melphalan intensification in
      multiple myeloma: an intrapatient controlled study.
AB  - A recent randomized multicentric French study has shown that intensification with
      stem cell rescue improves the response rate and progression-free survival in
      multiple myeloma. Transplantation with primed peripheral blood stem cells (PBSC)
      displays a faster hematological recovery, especially for platelets, as compared
      with a bone marrow stem cell graft. In multiple myeloma, the optimal mobilization
      method for PBSC is unknown. The present study compares mobilization with
      cyclophosphamide 4 g/m2 + G-CSF 5 micrograms/kg versus G-CSF 5 micrograms/kg
      alone versus G-CSF 10 micrograms/kg alone in two cases of multiple myeloma, using
      an intrapatient controlled evaluation of the amount of CD34-positive cells
      obtained during each leukapheresis. In both cases, the highest CD34-positive
      cells yield was obtained with G-CSF at 10 micrograms/kg. Despite the low number
      of cases, this method, devoid of life-threatening toxicity, might be of greatest
      interest in multiple myeloma.

PMID- 7522397
TI  - Infant with multiple congenital anomalies and deletion (9)(q34.3).
AB  - We report on a male infant with developmental delay, growth failure, hypotonia,
      dolichocephaly, hypoplastic midface, epicanthal folds, down-slanting palpebral
      fissures, foveal hypoplasia, tracheomalacia, pectus excavatum, supraventricular
      tachycardia, gut malrotation, hypospadias, talipes equinovarus, short third
      metatarsals, capillary hemangiomata, and a de novo terminal deletion at 9q34.3.

PMID- 7522398
TI  - Insulin-like growth factor-binding proteins in the human fetus: tissue-specific
      protein secretion, immunologic characterization, and gene expression.
AB  - OBJECTIVES: The objectives of this study were to investigate the profile of
      insulin-like growth factor-binding proteins secreted by human fetal tissues and
      their immunologic identification and tissue-specific gene expression. STUDY
      DESIGN: Explants of midgestational fetal tissues from seven fetuses were cultured
      with and without cycloheximide. Conditioned media were examined for insulin-like
      growth factor-binding proteins by Western ligand blot analysis, and insulin-like
      growth factor-binding proteins were identified by immunoprecipitation. Gene
      expression was analyzed by Northern analysis. RESULTS: Fetal liver and kidney
      explants secreted insulin-like growth factor-binding protein-1 to insulin-like
      growth factor-binding protein-4, with insulin-like growth factor-binding protein
      1 being the most prominent in liver. Fetal lung secreted insulin-like growth
      factor-binding protein-2 and insulin-like growth factor-binding protein-4 and
      lesser amounts of insulin-like growth factor-binding protein-3, whereas white
      matter explants secreted exclusively insulin-like growth factor-binding protein-2
      and insulin-like growth factor-binding protein-4. Cycloheximide inhibited
      secretion of binding proteins, suggesting de novo synthesis. Northern blot
      analyses were consistent with the protein studies. CONCLUSION: These data
      demonstrate that insulin-like growth factor-binding protein secretion by fetal
      tissues is tissue specific.

PMID- 7522399
TI  - Atrial natriuretic factor concentration in normal, growth-retarded, anemic, and
      hydropic fetuses.
AB  - OBJECTIVE: Our purpose was to establish a reference range with gestation for
      plasma concentrations of atrial natriuretic factor in fetal blood and to examine
      whether the concentration is altered in fetal anemia, acidemia, or hydrops. STUDY
      DESIGN: Atrial natriuretic factor was measured in umbilical venous blood taken by
      cordocentesis from pregnancies complicated by red blood cell isoimmunization (n =
      17), intrauterine growth retardation (n = 12), and hydrops fetalis (n = 20) and
      from controls (n = 66). Additionally, maternal blood atrial natriuretic factor
      concentration was measured in 40 uncomplicated pregnancies. RESULTS: In the
      control group detectable levels were found from 16 weeks onward, and the fetal
      plasma atrial natriuretic factor concentration did not change with gestation. In
      anemic, acidemic, and hydropic fetuses the concentration was higher than in
      controls. CONCLUSION: Fetuses are capable of producing atrial natriuretic factor
      under physiologic conditions, and the concentration is increased appropriately in
      pathologic states.

PMID- 7522400
TI  - Developmental regulation of the expression of 72 and 92 kd type IV collagenases
      in human trophoblasts: a possible mechanism for control of trophoblast invasion.
AB  - OBJECTIVE: During early pregnancy fetal cytotrophoblast cells invade the uterus
      and penetrate the basement membrane, a property that is characteristic of
      malignant cells. However, unlike tumor invasion, trophoblast invasion of the
      uterus is under strict control. This control limits invasion, so that it
      primarily remains confined to the endometrial aspect of the myometrium and
      continues only until midgestation. The invasive properties of the trophoblast
      cells are made possible by the activity of proteolytic enzymes that belong to the
      metalloproteinases and serine proteinases. Type IV collagenase
      (metalloproteinase) is considered crucial in the extracellular matrix remodeling
      that takes place during the invasion process. In this study we set out to
      characterize the invasive properties of trophoblast cells at different stages of
      pregnancy. STUDY DESIGN: Human trophoblast cells were isolated from first- and
      third-trimester placentas by trypsin digestion and Percoll fractionation and were
      then cultured under serum-free conditions. The invasive ability of trophoblast
      cells was determined by the in vitro invasion assay, in which the ability of
      cells to penetrate an artificial basement membrane was examined.
      Metalloproteinase activity was measured by zymography, and the expression of
      messenger ribonucleic acid transcripts of 72 and 92 kd type IV collagenases was
      examined by reverse transcriptase polymerase chain reaction. RESULTS: First
      trimester trophoblasts were 3.5 time more invasive in vitro than were third
      trimester trophoblast cells (p < 0.005). Although first-trimester trophoblasts
      secreted both species of type IV collagenase, 72 and 92 kd, in large amounts,
      third-trimester cells secreted the 92 kd and only minimal amounts of 72 kd type
      IV collagenase. Moreover, first-trimester trophoblasts secreted significantly
      more (p < 0.05) 92 kd type IV collagenase than did third-trimester trophoblast.
      The messenger ribonucleic acid transcript expression of 72 and 92 kd type IV
      collagenases correlated with the activity of these enzymes secreted by first- and
      third-trimester trophoblasts. CONCLUSION: The described high in situ invasive
      capacity of first-trimester trophoblast might be explained by the increased
      expression and production of 72 kd type IV collagenase and the higher expression
      of 92 kd type IV collagenase by first-trimester trophoblast cells.

PMID- 7522401
TI  - Induction of nitric oxide synthases early in pregnancy.
AB  - OBJECTIVE: We have previously demonstrated that calcium-dependent nitric oxide
      synthase is induced by estrogen and that by the end of pregnancy nitric oxide
      synthase of both endothelial and neuronal origin is increased in various maternal
      tissues. This rise in activity may be crucial for the alterations in muscle
      activity necessary for a successful pregnancy. If so, the increase in nitric
      oxide synthase activity must occur early in gestation. STUDY DESIGN: We tested
      the hypothesis that pregnancy increases nitric oxide synthase activity early in
      gestation by measuring in heart, kidney, skeletal muscle, and esophagus of time
      mated guinea pigs the conversion by nitric oxide synthase of carbon 14-labeled L
      arginine to carbon 14-labeled citrulline and the concentration of cyclic
      guanosine monophosphate, the second messenger of nitric oxide. RESULTS: Calcium
      dependent nitric oxide synthase activity was increased twofold to fourfold by
      pregnancy in each tissue examined. The rise began by 0.14 gestation (9 of 63 +/-
      2 days) and reached a plateau by 0.30 gestation (19 days), which was then
      maintained until term. The treatment of pregnant animals with tamoxifen decreased
      nitric oxide synthase activity to nonpregnant values in the heart, where
      tamoxifen is an estrogen receptor antagonist, but not in kidney, skeletal muscle,
      and esophagus. Cyclic guanosine monophosphate also rose progressively in each
      tissue studied until about 0.70 gestation before declining in skeletal muscle,
      kidney, and heart. It remained elevated in the esophagus. CONCLUSION: These
      studies demonstrate that nitric oxide synthase activity in maternal tissues rises
      early in pregnancy and is associated with an increase in cyclic guanosine
      monophosphate, the second messenger of nitric oxide. These findings are
      consistent with the hypothesis that an increase in nitric oxide synthase plays a
      role in smooth muscle adaptations of pregnancy.

PMID- 7522402
TI  - Tyrosine protein phosphorylation in plasma membranes of rat kidney cortex.
AB  - The endogenous tyrosine protein kinase activity (TPKA) associated with brush
      border (BBM) and basolateral (BLM) membranes of rat kidney cortex was studied
      with an anti-phosphotyrosine monoclonal antibody (PY20). Distinct major
      phosphotyrosine-containing proteins were associated with BBM (50, 54, and 120
      kDa) and BLM (37, 90, 130, and 170 kDa). For both plasma membranes, tyrosine
      phosphorylation leveled off after 10 min of incubation. Endogenous
      phosphotyrosine-specific protein phosphatases (PT-Pases) were active in both
      membranes, since the presence of sodium vanadate or ammonium molybdate, which are
      inhibitors of PTPases, was essential to detect endogenous phosphorylation.
      Substrates and/or tyrosine protein kinases (TPKs) seem to be differently
      distributed in these plasma membranes, since phosphorylation of endogenous
      substrates in BLM and BBM was differently sensitive to competitive inhibitors of
      TPKs. Moreover, insulin- and insulin-like growth factor I-stimulated tyrosine
      phosphorylation of a 90-kDa substrate was only observed in solubilized BLM
      proteins. However, similar p60v-src-related TPKs appear to be present in the BBM
      and BLM, since an antibody raised against p60v-src recognized proteins of 52, 58,
      and 75 kDa by immunoblotting and could immunoprecipitate the TPKs associated with
      both plasma membranes. These data provide evidence that the endogenous tyrosine
      protein phosphorylation observed in the BLM is catalyzed by nonreceptor TPKs as
      well as receptor TPKs, whereas that observed in the BBM is exclusively due to
      nonreceptor TPKs.

PMID- 7522403
TI  - Histamine can induce leukocyte rolling in rat mesenteric venules.
AB  - Rolling is a retarded movement of leukocytes that depends on the function of the
      selectin class of adhesion molecules. In venules of internal organs, rolling is
      rapidly induced on tissue exposure by unknown mediator(s). Rolling was
      investigated with intravital microscopy in venules of the exteriorized mesentery
      of anesthetized rats. Immediately after exteriorization, rolling leukocyte flux
      was very low (10 +/- 4 min-1) and increased rapidly to reach a peak of 76 +/- 10
      min-1 at 30 min. Intraperitoneal pretreatment of rats with histamine induced near
      maximal rolling in mesenteric venules immediately after exteriorization.
      Leukocyte rolling was significantly inhibited by intravenular microinfusion of
      monoclonal antibody PB1.3 that recognizes and functionally blocks human and rat P
      selectin. The effect of histamine was blocked by pretreatment with ranitidine, an
      H2-receptor antagonist, but not with diphenhydramine, which blocks H1 receptors.
      However, ranitidine did not block the subsequent increase of rolling leukocyte
      flux, and rolling leukocyte flux was similar in all groups 20 min after
      exteriorization. Histological investigation revealed degranulation of mast cells,
      suggesting release of histamine and other mediators. These findings indicate that
      histamine can induce leukocyte rolling in vivo via H2 receptors, most likely by
      inducing endothelial expression of P-selectin. In addition, mediators other than
      histamine released from mast cells and/or other cells are likely to promote
      sustained rolling.

PMID- 7522404
TI  - Geometry of coronary capillaries in hyperthyroid and hypothyroid rat heart.
AB  - Coronary capillary geometry was studied in male rats treated with 3,3',5-triiodo
      L-thyronine (T3; Hyper), 6-N-propyl-2-thiouracil (PTU; Hypo), or a sequence of
      PTU and T3 (Hypo/Hyper). Ventricular mass and heart-to-body mass ratios revealed
      myocardial hypertrophy in Hyper, atrophy in Hypo, and a return of ventricular
      mass to control (Con) values in Hypo/Hyper rats. From cross-sectional analysis,
      capillary densities for Hyper and Hypo/Hyper were comparable with Con, despite
      increased left ventricular mass. Hypo rats demonstrated increased capillary
      density. In Hyper and Hypo rats, tissue area surrounding individual capillaries
      (capillary domain) decreased, compared with Con, for capillaries close to the
      feeding arteriole. In Hyper and Hypo/Hyper, capillaries distal to the feeding
      arteriole had similar domain areas as Con; in Hypo, this area was smaller. From
      longitudinal analysis, capillary segment lengths were significantly shorter in
      all groups compared with Con. Our data suggest that while hypothyroidism induced
      myocardial atrophy and hyperthyroidism induced myocardial hypertrophy, both
      thyroid states stimulated capillary proliferation.

PMID- 7522405
TI  - Thrombin receptor peptide-mediated leukocyte rolling in rat mesenteric venules:
      roles of P-selectin and sialyl Lewis X.
AB  - Neutrophil adhesion to monolayers of cultured endothelial cells is enhanced, via
      a P-selectin-mediated mechanism, by a 14-amino acid peptide fragment (TRP-14) of
      the thrombin receptor. The objective of this study was to determine whether TRP
      14 promotes P-selectin-mediated sialyl Lewis X-dependent leukocyte rolling in
      postcapillary venules. Superfusion of the rat mesentery with TRP-14 for 30 min
      resulted in the recruitment of rolling leukocytes and a concomitant reduction in
      leukocyte rolling velocity. Analogues of TRP-14 were largely ineffective in
      promoting leukocyte-endothelial cell adhesion. Treatment with either a monoclonal
      antibody directed against rat P-selectin or soluble sialyl Lewis X
      oligosaccharide (the carbohydrate ligand to P-selectin found on leukocytes)
      significantly attenuated the TRP-14-induced recruitment of rolling leukocytes.
      However, no effect was observed with a nonbinding antibody or a control fucose
      deficient oligosaccharide. These results indicate that TRP-14 elicits the
      recruitment of rolling leukocytes in postcapillary venules via a P-selectin
      dependent mechanism. The results also support the view that sialyl Lewis X
      participates in P-selectin-mediated leukocyte-endothelial cell adhesion.

PMID- 7522407
TI  - Human basilar and middle cerebral arteries exhibit endothelium-dependent
      responses to peptides.
AB  - We examined the activities of bradykinin, substance P, and vasopressin in
      isolated human cerebral arteries to better understand humoral control of
      cerebrovascular tone. Basilar and middle cerebral arteries were isolated from
      human cadavers during autopsy, and isometric tension was measured in helical
      strips of the arteries. Both bradykinin and substance P relaxed strips of both
      arteries precontracted with prostaglandin F2 alpha to similar extents. The
      relaxations induced by both peptides were abolished by removal of the vascular
      endothelium and were markedly reduced by pretreatment with NG-nitro-L-arginine,
      an inhibitor of endothelium-derived relaxing factor. Treatment with indomethacin,
      a cyclooxygenase inhibitor, did not attenuate the relaxations. These results
      indicate that the responses of human cerebral arteries to bradykinin and
      substance P are mediated by endothelium-derived relaxing factor. In contrast,
      vasopressin primarily produced endothelium-independent contractions in human
      cerebral arteries. Contractions of basilar arteries induced by vasopressin were
      much less than those of middle cerebral arteries. Two of eighteen basilar
      arteries, but none of the middle cerebral arteries, responded to vasopressin with
      endothelium-dependent relaxation. This suggests that the function of vasopressin
      receptors differs in basilar and middle cerebral arteries.

PMID- 7522408
TI  - NO donors prevent integrin-induced leukocyte adhesion but not P-selectin
      dependent rolling in postischemic venules.
AB  - The objective of this study was to examine the effect of nitric oxide (NO) donors
      on polymorphonuclear leukocyte (PMN) interactions in the microvasculature of
      postischemic tissue and to compare the antiadhesive properties of NO donors with
      the responses observed after immunoneutralization of three key adhesion
      glycoproteins (CD11/CD18, intercellular adhesion molecule-1, and P-selectin).
      Rolling and firm adhesion (adherence) of leukocytes and shear rate were monitored
      in cat mesenteric venules subjected to 60 min of ischemia (blood flow reduced to
      20% of control), followed by 60 min of reperfusion. Immediately before
      reperfusion, the mesentery was superfused with a NO donor (3-morpholinosydonimine
      N-ethyl-carbamide or spermine-NO) or a monoclonal antibody (MAb) against an
      adhesion glycoprotein that was administered intravenously. In untreated animals,
      a profound influx in rolling PMNs was observed during reperfusion that was
      subsequently followed by increased firm adhesion. The anti-P-selectin antibody
      completely abolished the rise in the flux of rolling PMNs, whereas the anti-CD18
      antibody prevented firm adhesion. Both NO donors attenuated ischemia/reperfusion
      induced leukocyte adhesion to a level comparable with that observed after
      administration of a MAb against CD11/CD18 without affecting PMN rolling. The
      antiadhesive effect of the NO donors could not be attributed solely to an
      improvement of venular wall shear rate. In vitro data did not reveal a direct
      effect of NO donors on the expression of CD18 or neutrophil adhesion to
      endothelial cells. These observations suggest that NO donors may provide
      protection from tissue injury by preventing PMN adhesion.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7522406
TI  - Calcium entry and myogenic phenomena in skeletal muscle arterioles.
AB  - Studies were conducted to examine Ca2+ entry in several vasomotor situations
      related to myogenic properties of arterioles (basal tone, vasomotion, and
      responsiveness to alterations in intravascular pressure). In vivo studies were
      performed on small cremaster muscle arterioles of anesthetized rats.
      Intravascular pressure was increased using the pressure-box technique. Voltage
      operated Ca2+ channel (VOC) activity was inhibited by nifedipine or
      methoxyverapamil and was stimulated with BAY K 8644. To examine the effect of
      hyperpolarization, studies were performed in the presence of pinacidil.
      Nifedipine and methoxyverapamil exhibited a trend toward dose-dependent dilation;
      however, neither agent caused dilation comparable to adenosine (10(-4) M). BAY K
      8644 produced a biphasic effect, constriction below 10(-8) M, and dilation at
      higher levels. These data indicate that basal tone can be modulated by agents
      acting on VOCs; however, as high concentrations of nifedipine do not abolish
      tone, other mechanisms contribute. At similar concentrations, the Ca2+ channel
      antagonist significantly inhibited vasomotion, abolishing vasomotion at
      concentrations above 5 x 10(-6) M. In contrast, BAY K 8644 caused a dose
      dependent increase in vasomotion amplitude (e.g., 269 +/- 52% of basal at 10(-7)
      M). Thus vasomotion appears highly dependent on VOCs. Experiments performed in
      the presence of the antagonists/agonists indicated that VOCs are not the prime
      determinant of constrictor responses to acute increases in intravascular
      pressure. Exposure to pinacidil resulted in dose-dependent vasodilatation and
      inhibition of vasomotion while showing little effect on acute myogenic responses.
      Similar effects of pinacidil were observed in isolated, cannulated, cremaster
      arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522410
TI  - Serotonergic activity is depressed in the ventromedial hypothalamic nucleus of 12
      day-old obese Zucker rats.
AB  - We previously reported lower ventromedial hypothalamic nucleus (VMN) serotonergic
      activity in 11-wk genetically obese vs. lean Zucker rats. To determine whether
      the activity was secondary to metabolic alterations associated with this
      established obesity (e.g., significant hyperphagia and hyperinsulinemia), we
      examined monoaminergic activity in various brain nuclei of 12-day lean (Fa/Fa and
      Fa/fa) and obese (fa/fa) rats early in the development of obesity. Obese pups had
      greater percent carcass fat than heterozygotes, both of which were fatter than
      homozygous lean rats. Obese, but not heterozygous lean, pups were
      hyperinsulinemic vs. Fa/Fa pups. VMN 5-hydroxy-3-indoleacetic acid levels, an
      index of serotonin release, were lower in obese and heterozygous than in
      homozygous lean pups and were not correlated with plasma insulin levels. Although
      monoamine differences also occurred in several other nuclei, for the most part
      they appeared to be unrelated to the obese genotype. We conclude that blunted VMN
      serotonergic activity is not secondary to the obese rat's hyperinsulinemia and
      may play a significant role in the development of obesity.

PMID- 7522411
TI  - Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control
      in nonhuman primates.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      behavior and serotonin by using a nonhuman primate model of aggression and
      impulse control. METHOD: During a routine capture and medical examination, 26
      adolescent male rhesus macaques (Macaca mulatta) were selected as subjects from a
      free-ranging population of 4,500 rhesus monkeys inhabiting a 475-acre sea island.
      Physiological data were obtained from 22-23 of the subjects. Blood and CSF
      samples were obtained, and each subject was fitted with a radio transmitter
      collar for rapid location. The subjects were released into their social groups,
      and quantitative behavioral observations were made over a 3-month period.
      RESULTS: CSF 5-hydroxyindoleacetic acid (5-HIAA) concentrations were inversely
      correlated with "escalated" aggression, i.e., a measure of more intense or severe
      aggression as defined by the ratio of chases and physical assaults to all
      aggressive acts. CSF 5-HIAA concentrations were significantly lower in those
      subjects who showed evidence of physical wounding than in subjects with no
      wounds. Low CSF 5-HIAA concentrations were also correlated with greater risk
      taking as determined by an analysis of leaping behaviors in the forest canopy.
      The ratio of long leaps (leaps that traversed the longest distances at dangerous
      heights) to all leaps was negatively correlated with CSF 5-HIAA concentrations.
      CONCLUSIONS: Adolescent male rhesus macaques with low CSF 5-HIAA concentrations
      are at risk for 1) exhibiting more violent forms of aggressive behavior and 2)
      loss of impulse control as evidenced by greater risk taking during movement
      through the forest canopy.

PMID- 7522412
TI  - A novel panel of antibodies that segregates immunocytochemically poorly
      differentiated carcinoma from undifferentiated carcinoma of the thyroid gland.
AB  - The expression of bcl-2 and p53 was investigated by immunocytochemistry in
      combination with that of conventional structural and differentiation antigens on
      the archival material of 22 cases of undifferentiated carcinoma (UC) and 19 of
      poorly differentiated carcinoma (PDC) of the thyroid gland. The restriction of
      bcl-2 expression to PDC in comparison to UC was 84.2% versus 13.6% of cases,
      respectively, in contrast to an almost equal percentage of p53 expression in the
      two histologic types, that is, 52.6% and 54.5% of cases of PDC and UC,
      respectively. However, the pattern of distribution of p53-immunoreactive cells
      was definitely different, being restricted to areas showing active infiltrating
      growth in PDC and involving almost all tumor cells in UC. Furthermore, in the
      subset of cases of UC showing the residual presence of a differentiated
      component, a distinctive mutual exclusion of bcl-2 and p53 immunoreactivity was
      observed in the two components. The results suggest that the evaluation of bcl-2
      expression may be usefully applied to the differentiation of PDC from UC, whereas
      all morphologic findings related to p53 expression are in keeping with a
      significant role of the deregulation of this gene in the mechanism of
      dedifferentiation and progression of the disease.

PMID- 7522409
TI  - Cooling and pH jump-induced calcium release from isolated cardiac sarcoplasmic
      reticulum.
AB  - Rapid-cooling contracture in cardiac muscle preparations is thought to be caused
      by the release of Ca2+ from the sarcoplasmic reticulum (SR), but the mechanism of
      this release is unknown. Cooling of isolated canine cardiac SR from 37 to 4
      degrees C resulted in the net release of enough Ca2+ to account for rapid-cooling
      contracture. The release of Ca2+ on cooling appeared to be a relaxation between
      different steady-state levels of Ca2+ uptake. Cooling release of Ca2+ was also
      observed in the presence of ryanodine or ruthenium red to block the ryanodine
      sensitive Ca2+ efflux pathway. In the presence of ryanodine, the extent and
      initial rate of rapid-cooling release were increased due to increased steady
      state uptake of Ca2+ by the SR. The first-order rate constant of rapid-cooling
      Ca2+ release was unchanged by ryanodine or ruthenium red, suggesting that the
      rapid-cooling release does not occur through the ryanodine-sensitive pathway. The
      alkalinization on cooling was not the major cause of the Ca2+ release, as
      comparable Ca2+ release was observed with cooling and no alkalinization. However,
      alkalinization without cooling produced a rapid net Ca2+ release, which was also
      observed in the presence of ryanodine.

PMID- 7522413
TI  - Consensus statement on terminology: recommendation to use atypical adenomatous
      hyperplasia in place of adenosis of the prostate.

PMID- 7522414
TI  - Adenosis vs. atypical adenomatous hyperplasia of the prostate.

PMID- 7522416
TI  - Solitary fibrous tumor. Consistent CD34 immunoreactivity and occurrence in the
      orbit.
AB  - The distinction of solitary fibrous tumors (SFTs) from histologically similar
      neoplasms relies heavily on a characteristic microscopic appearance. No
      discriminating ultrastructural or immunohistochemical features are known. We
      evaluated 22 SFTs and 118 other tumors often considered in the differential
      diagnosis for immunoreactivity using a monoclonal antibody directed against the
      human hematopoietic progenitor cell antigen, CD34. All the SFTs (22 of 22, 100%)
      demonstrated strong CD34 immunoreactivity, irrespective of tumor site and
      histologic grade. Strong and generalized CD34 positivity was also found in most
      dermatofibrosarcoma protuberans (11 of 12, 92%) and occasional smooth-muscle
      tumors (leiomyomas 2 of 11, 18%; leiomyosarcomas 2 of 11, 18%). Variable numbers
      of CD34 positive cells were present in all neurofibromas (9 of 9, 100%) and
      focally present in most schwannomas (8 of 9, 89%). Some of the
      hemangiopericytomas (7 of 16, 44%) exhibited CD34 immunoreactivity, however,
      generally with weak intensity and patchy distribution. CD34 immunoreactivity was
      not observed in mesotheliomas (0 of 20, 0%), synovial sarcomas (0 of 13, 0%),
      fibrosarcomas (0 of 12, 0%), or spindle-cell thymomas (0 of 5, 0%). We conclude
      that CD34 immunoreactivity is a sensitive marker for SFT and, in conjunction with
      an appropriate immunohistochemical panel, may be useful in discriminating SFTs
      from other histologically similar neoplasms. The observation that some
      mesenchymal stromal cells and SFTs share a CD34-positive immunophenotype suggests
      a histogenetic relationship. The inclusion in this study of two cases of SFTs
      arising in the orbit establishes another site of origin for this tumor and
      provides further support for a mesenchymal histogenesis.

PMID- 7522415
TI  - Clinical and pathobiological effects of neoadjuvant total androgen ablation
      therapy on clinically localized prostatic adenocarcinoma.
AB  - Neoadjuvant total androgen ablation therapy leads to involutional changes in
      prostatic carcinoma and may have the potential to downstage operable prostate
      cancers. We studied 27 clinically localized prostatic carcinomas after 3 months
      of combined treatment with a luteinizing hormone-releasing hormone agonist,
      goserelin acetate, and the antiandrogen flutamide, followed by radical retropubic
      prostatectomy, for changes in the serum prostate-specific antigen (PSA) level,
      changes in prostatic volume, therapy-induced histopathologic changes, DNA ploidy,
      and proliferative activity. Ten hormonally untreated, grade-matched prostatic
      adenocarcinomas served as controls. The mean pretherapy serum PSA level was 17.5
      ng/ml, and posttherapy PSA levels were all < 4.0 ng/ml, with 18 men having
      undetectable levels. The mean reduction in prostatic volume following hormonal
      therapy was 37% (range 16-52%). Pathologic staging confirmed 20 pT2N0, six pT3N0,
      and one pT3N1. All prostates showed residual adenocarcinoma (extremely focal in
      seven cases [26%] with loss of glandular architecture, cytoplasmic vacuolization,
      and nuclear pyknosis. High-grade adenocarcinoma was nondiploid in 25% of
      hormonally treated prostates and 80% of 10 untreated controls. Immunostaining for
      proliferating cell nuclear antigen showed > 10% nuclear reactivity in 33% of
      treated carcinomas and 90% of untreated carcinomas. In conclusion, 3 months of
      neoadjuvant androgen ablation for localized prostatic carcinoma significantly
      lowers serum PSA and prostatic volume and produces involutional changes in
      residual carcinomas that mimic high-grade disease. However, pretreated carcinomas
      have predominantly a diploid DNA content and low proliferative activity as
      opposed to untreated carcinomas. Thus, grading of pretreated adenocarcinomas by
      conventional methods may be misleading. Preoperative total androgen ablation has
      a profound effect on a subset of prostatic carcinoma cells, possibly by
      facilitating programmed cell death.

PMID- 7522417
TI  - Immunotherapy with T-cell-reactive peptides derived from allergens.

PMID- 7522418
TI  - IgE and IgG4 binding to the ocelot variant of the cat (Felis domesticus) major
      allergen Fel d I.

PMID- 7522419
TI  - Optical biosensor for monitoring microbial cells.
AB  - The potential of a new optical biosensor, the resonant mirror, for detecting
      whole cells is demonstrated. Staphylococcus aureus (Cowan-1) cells, which express
      protein-A at their surface, were detected by binding to human immunoglobulin G
      (IgG) immobilized on an aminosilane-derivatized sensor surface at concentrations
      in the range 8 x 10(6)-8 x 10(7) cells/mL. A control S. aureus strain (Wood-46),
      which does not express protein-A, gave no significant response. Immobilization of
      the capture ligand on aminosilane surfaces with and without a hydrogel coating of
      carboxymethyl-dextran was compared. The greatest binding response was observed
      with non-dextran-coated surfaces. The sensitivity of the technique was increased
      a 1000-fold by using a human IgG-colloidal gold conjugate (30 nm) in a sandwich
      assay format. S. aureus (Cowan-1) cells were detected in spiked milk samples at
      cell concentrations from 4 x 10(3)-1.6 x 10(6) cells/mL using the sandwich assay.

PMID- 7522421
TI  - Distribution of glial fibrillary acidic protein-immunopositive structures in the
      brain of the red-eared freshwater turtle (Pseudemys scripta elegans).
AB  - The distribution of glial fibrillary acidic protein (GFAP)-immunoreactivity is
      described in serial Vibratome sections of the turtle brain. The results are
      discussed in relation to our previous studies of rat and chicken brains. In the
      turtle brain, the distribution of GFAP-positive elements is rather evenly
      abundant as compared to that observed in the chicken and rat. The GFAP-positive
      structures are fibers of different length and orientation, but the stellate cells
      are not GFAP-positive. The basic systems is the radial ependymoglia, directed
      from the ventricles toward the outer surface of the brain. This system also
      contains some transverse and randomly oriented fibers. The cell bodies are not
      usually GFAP-positive. The large brain tracts could be recognized by their weak
      immunostaining, but gray matter nuclei could not be identified on the basis of
      immunostaining against GFAP. The layers of the optic tectum could be
      distinguished, as well as the gray and white matter of brain stem and spinal cord
      and the molecular and granular layers of the cerebellum. In the cerebellum, a
      fiber system resembling the Bergmann-fibers, a strong midline raphe and coarse
      transverse fibers could be observed. These latter fibers have no equivalent in
      other cerebella. Their perikarya proved also to be GFAP-positive, and seemed to
      be dividing in the adult turtle brain. We conclude that the appearance of GFAP
      positive stellate cells had a great importance in the evolution of avian and
      mammalian brains strengthening the thicker brain walls and assisting in the
      formation of local differences of GFAP-immunoreactivity in different brain areas.

PMID- 7522422
TI  - [Can hydroxyethylamidon be used during intensive care of brain-dead organ
      donors?].
AB  - In France, most of the kidney grafts are obtained from brain dead organ donors.
      Brain death induces numerous changes, especially in haemodynamic status,
      requiring the infusion of large volumes of fluid. The aim of this study was to
      evaluate the effect of hydroxyethyl starch (HES) on the organ donors and the
      kidney graft function in recipients. We compared two groups of brain dead organ
      donors and the kidney grafts, differing by the infused solutions: either a
      combination of HES (Elohes, Biosedra) and 4% human albumin solutions (HES group),
      or albumin alone in the control group (Albumin group). In the two groups, sex
      ratio, age, cause of brain death and duration of therapy were similar. Fluid
      requirements were identical in the two groups: respectively 2,211 +/- 1,512 mL in
      the Albumin group vs 2,452 +/- 1,094 mL in the HES group (p = 0.17). However, the
      volume of albumin was significantly decreased in the HES group: 711 +/- 822 mL (p
      = 0.0001). Therefore the cost was lower in the latter: 638 +/- 633 vs 1766 +/-
      788 FF. The coagulation status was not significantly different between the two
      groups. Amylasemia was higher in the HES group, but the difference was not
      significant. In the Albumin group, urinary output increased, but not
      significantly and creatinemia was decreased: 113.9 +/- 62 vs 131.5 +/- 44 mumol.L
      1 (p < 0.05). The two groups of recipients were also similar for sex-ratio, age,
      kind of graft, cause of the chronic renal failure and ischaemia times.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7522423
TI  - Base excision repair in E. coli--an overview.

PMID- 7522424
TI  - Biological responses of human apurinic endonuclease to radiation-induced DNA
      damage.

PMID- 7522420
TI  - Neurofilament expression in lens cells of the house shrew, Suncus murinus.
AB  - Immunohistochemical analysis demonstrated that lens cells of the laboratory house
      shrew, Suncus murinus, expressed many intracellular filaments that immunoreacted
      with pooled monoclonal antibodies against 70-kDa, 160-kDa, and 210-kDa
      neurofilament triplet proteins. Immunopositive filaments in lens cells first
      appeared in day 13 embryos, while the invaginating lens placode was thickening,
      and this immunoreactivity was still present in immature lens fiber cells of the
      adult animal. Western blot analysis showed that the immunopositive molecule was a
      low-molecular-weight neurofilament protein that appeared in the neural tissues of
      this animal. The immunoreactive pattern of lens cells was quite similar to that
      of neurons, although there were some peculiar aspects. When the cells of the lens
      vesicle differentiated into the lens epithelium and fibers, immunoreactivity
      occurred in both, suggesting that the neurofilaments in the lens cells do not
      directly relate to lens fiber elongation nor to a determinant of the fiber
      caliber. The strong immunoreactivity in the embryonic lens and weak expression of
      this protein in the immature lens fiber cells of the adult animal suggest that
      low-molecular-weight neurofilament protein is transiently expressed in the
      differentiating lens cells. This may be a common feature of placode-derived
      cells.

PMID- 7522426
TI  - [Value of the characterization of cytokeratins in the oropharyngeal epithelium].
AB  - Cytokeratins are cytoskeletal components and constitute the intermediate
      filaments of epithelial cells. They are twenty in number and their distribution
      characterizes a very specific profile in each kind of epithelium. The authors
      characterized the cytokeratin repartition of the normal oropharyngeal epithelia
      in order to study their alterations in pathologic tissues, especially in
      neoplastic and dysplastic epithelia. The normal oropharyngeal epithelium shows
      cytokeratin pattern of non keratinized stratified epithelia. Three mucosa samples
      were studied from inflammatory, dysplastic and neoplastic epithelia. According to
      the alterations of cytokeratin repartition in the two last samples, cytokeratin
      pattern analysis could allow a characterization or the differentiation stage of
      neoplastic tissues before the expression of morphogenic criteria.

PMID- 7522425
TI  - Efficient bypass and base misinsertions at abasic sites by prokaryotic RNA
      polymerases.

PMID- 7522428
TI  - Susceptibilities of human immunodeficiency virus type 1 enzyme and viral variants
      expressing multiple resistance-engendering amino acid substitutions to reserve
      transcriptase inhibitors.
AB  - To evaluate the potential that multiply resistant human immunodeficiency virus
      type 1 variants may arise during combination nucleoside and nonnucleoside reverse
      transcriptase inhibitor therapy, we constructed a series of mutant reverse
      transcriptase enzymes and viruses that coexpressed various combinations of
      resistance-associated amino acid substitutions. Substitutions at residues 100
      (Leu-->Ile) and 181 (Tyr-->Cys), which mediate resistance to the nonnucleosides,
      suppressed resistance to 3'-azido-3'-deoxythymidine (AZT) when coexpressed with
      AZT-specific substitutions. However, a number of viral variants that exhibited
      significantly reduced susceptibilities to both classes of inhibitors were
      constructed.

PMID- 7522429
TI  - Novel mutation (V75T) in human immunodeficiency virus type 1 reverse
      transcriptase confers resistance to 2',3'-didehydro-2',3'-dideoxythymidine in
      cell culture.
AB  - We have selected a human immunodeficiency virus type 1 (HIV-1) mutant strain with
      a moderate (sevenfold) level of resistance to the nucleoside analog 2',3'
      didehydro-2',3'-dideoxythymidine (D4T or stavudine). After serial passage of the
      HXB2 strain of HIV-1 in MT4 cells, a novel mutation involving two nucleotide
      substitutions in codon 75 of the viral reverse transcriptase, altering valine to
      threonine, was seen. When introduced into a wild-type HIV-1 background by site
      directed mutagenesis, the T-75 mutation conferred cross-resistance to the
      dideoxynucleosides dideoxyinosine and dideoxycytosine as well as to 2',3'
      didehydro-2',3'-dideoxycytosine.

PMID- 7522430
TI  - Risk of fetal Down's syndrome based on maternal age and varying combinations of
      maternal serum markers.
AB  - Serum samples from 320 women with chromosomally normal fetuses and from 50 women
      with fetuses affected by Down's syndrome were assayed retrospectively for human
      chorionic gonadotropin (hCG), pregnancy-specific beta 1 glycoprotein (SP1), alpha
      fetoprotein (AFP), and unconjugated estriol (uE3) between 14 and 21 weeks of
      gestation. Nonparametric discriminant analysis was applied to calculate Down
      syndrome risks on the basis of various combinations of serum parameters. At a
      risk threshold that falsely identifies 5% of controls as being affected, 46 to
      48% of Down syndrome pregnancies were detected by combinations of hCG/AFP,
      hCG/AFP/uE3, and hCG/AFP/uE3/SP1 respectively. HCG, AFP, and uE3 were assayed in
      652 serum samples from women who underwent amniocentesis because of maternal age
      (> or equal to 35 years in this prospective study). 49% of women with euploid
      fetal karyotype, 8 of 10 pregnancies with Down's syndrome, and 3 pregnancies with
      sex chromosomal anomalies were identified as being at an increased risk (>
      1:380).

PMID- 7522432
TI  - Patient requests to hasten death. Evaluation and management in terminal care.
AB  - Terminally ill patients often hope that death will come quickly. They may broach
      this wish with their physicians, and even request assistance in hastening death.
      Thoughts about accelerating death usually do not reflect a sustained desire for
      suicide or euthanasia, but have other important meanings that require
      exploration. When patients ask for death to be hastened, the following areas
      should be explored: the adequacy of symptom control; difficulties in the
      patient's relationships with family, friends, and health workers; psychological
      disturbances, especially grief, depression, anxiety, organic mental disorders,
      and personality disorders; and the patient's personal orientation to the meaning
      of life and suffering. Appreciation of the clinical determinants and meanings of
      requests to hasten death can broaden therapeutic options. In all cases, patient
      requests for accelerated death require ongoing discussion and active efforts to
      palliate physical and psychological distress. In those infrequent instances when
      a patient with persistent, irremediable suffering seeks a prompt and comfortable
      death, the physician must confront the moral, legal, and professional
      ramifications of his or her response. Rarely, acceding to the patient's request
      for hastening death may be the least terrible therapeutic alternative.

PMID- 7522427
TI  - Effects of U-75875, a peptidomimetic inhibitor of retroviral proteases, on simian
      immunodeficiency virus infection in rhesus monkeys.
AB  - U-75875 inhibits human immunodeficiency virus types 1 and 2 and simian
      immunodeficiency virus (SIV) proteases and blocks Gag-Pol protein processing and
      viral maturation and replication in vitro. Rhesus monkeys were treated with
      vehicle alone or with formulated U-75875 at doses of 7 or 20 mg/kg of body weight
      per day for 26 days by continuous intravenous infusion beginning 6 h prior to
      intravenous inoculation with 10 monkey 50% infectious doses of SIV Delta B670,
      and the monkeys were monitored until death. The effects of treatment on the level
      of SIV p26 antigenemia, the infectious virus titer in serum, and the level of
      proviral DNA in blood mononuclear cells evaluated by PCR were assessed. SIV
      infection of the controls resulted in an initial viral antigenemia that began 5
      to 10 days postinoculation (p.i.), reached peak values on days 10 to 14 p.i., and
      lasted for more than 15 days. Proviral DNA was detectable in peripheral blood
      mononuclear cells by 7 to 11 days p.i., reached the mean peak level by 11 days
      p.i., and remained at high levels through day 24 p.i. Infectious virus was
      detected in serum from all of the infected controls by 24 days p.i. Treatment
      with U-75875 for 26 days resulted in a dose-related delay in the day of the peak
      level of antigenemia (P = 0.034). The level of proviral DNA in peripheral blood
      mononuclear cells at 11 days p.i. was significantly decreased in a dose-related
      fashion in the treated monkeys ( P </- 0.048), with a delay in the attainment of
      the peak level of proviral DNA in the treated groups. The titer of infectious
      virus in the serum of the group treated with 20 mg/kg/day was significantly
      decreased on day 24 p.i. compared with that in the serum of controls ( P =
      0.046). Treatment with formulated U-75875 was well tolerated in rhesus monkeys
      and resulted in an inhibitory effect of SIV in vivo.

PMID- 7522433
TI  - Effects of human serum supplementation on fertilization and development of mouse
      embryos.
AB  - Serum is generally used as a protein supplement in culture media for human in
      vitro fertilization (IVF). To determine the effects of serum supplementation on
      the development of preimplantation embryos, one-cell and two-cell mouse embryos
      fertilized in vitro and in vivo were cultured in BWW medium supplemented with
      preovulatory patient serum (PS), human fetal cord serum (HCS), or bovine serum
      albumin (BSA). The rates of fertilization and development of embryos fertilized
      in vitro and in vivo were suppressed when the embryos were cultured with PS or
      HCS as compared with BSA. In the medium supplemented with HCS, growth of in vitro
      fertilized embryos was retarded at an earlier embryonic stage than was the case
      with embryos fertilized in vivo. These results suggest that the in vitro
      fertilized embryo culture model is more sensitive to culture conditions than is
      the in vivo fertilized embryo culture model. Incorporations of [3H]uridine and
      [3H]leucine were measured using embryos that developed to the blastocyst stage in
      a medium supplemented with HCS or BSA. Blastocysts cultured with HCS showed
      significantly higher incorporations of [3H]uridine and [3H]leucine than those
      cultured with BSA. While serum supplementation in culture media has adverse
      effects on embryo cleavage, it augments synthesis of RNA and protein.

PMID- 7522431
TI  - Single-center experience with primary orthotopic liver transplantation with FK
      506 immunosuppression.
AB  - OBJECTIVE: The efficacy for primary orthotopic liver transplantation of a new
      immunosuppressive agent, FK 506 (tacrolimus, Prograf, Fujisawa USA, Deerfield,
      IL), was determined. SUMMARY BACKGROUND DATA: After 3 years of preclinical
      research, a clinical trial of FK 506 for orthotopic liver transplantation was
      begun in February 1989, first as a rescue therapy for patients with intractable
      rejection with conventional immunosuppression, then as a primary drug. METHODS:
      Between August 1989 and December 1993, 1391 recipients (1188 adult and 203
      pediatric) of primary liver allografts were treated with FK 506 from the outset.
      Results from these patients were analyzed and compared with those of 1212
      historical control patients (971 adult and 241 pediatric) given cyclosporine
      based immunosuppression. RESULTS: Actuarial survival at 4 years was 86.2% with FK
      506 versus 65.5% with cyclosporine in the pediatric patients (p < 0.0000) and
      71.4% versus 65.5% in the adults (p < 0.0005). The need for retransplantation was
      reduced significantly for FK 506 patients. Four-year graft survival was 77.0%
      with FK 506 versus 48.4% with cyclosporine in the pediatric patients (p <
      0.0000), and 61.9% with FK 506 versus 51.4% with cyclosporine in the adult
      recipients (p < 0.0000). Regression analysis revealed that reduction in mortality
      or graft loss from uncontrollable rejection, sepsis, technical failure, and
      recurrent original liver disease were responsible for the improved results with
      FK 506 therapy. CONCLUSIONS: FK 506 is a potent and superior immunosuppressive
      agent for orthotopic liver transplantation.

PMID- 7522434
TI  - Hormone-nuclear receptor interactions in health and disease. The oestrogen
      receptor.
AB  - During the past 30 years, we have learned a great deal about the molecular
      details whereby the ovarian hormone elicits the feminizing effects that Knauer
      described in his experiments over a century ago. The ER plays a pivotal role in
      this process, and potentially in many other physiological processes. The roles of
      variant receptors, the details of ER-mediated transactivation and the regulation
      of ER expression and activation are just a few of the important unresolved issues
      in this field. These are not trivial problems, and their solutions are likely to
      require much more investigation. This information will provide important clinical
      insight into breast cancer, lipid metabolism, bone metabolism, prostatic
      hyperplasia and other diseases. Armed with this basic knowledge, scientists will
      be better equipped to design rational therapeutic and preventive strategies to
      combat these major clinical problems.

PMID- 7522435
TI  - Recruitment of mitochondrial cyclophilin to the mitochondrial inner membrane
      under conditions of oxidative stress that enhance the opening of a calcium
      sensitive non-specific channel.
AB  - Binding of mitochondrial matrix cyclophilin (CyP) to the rat liver mitochondrial
      membranes was detected by SDS/PAGE and Western blotting with suitable antipeptide
      antibodies. Binding was not affected by prior exposure of mitochondria to Ca2+,
      adenine nucleotides or inhibitors of the adenine nucleotide translocase, but was
      greatly increased by t-butyl hydroperoxide (tBH), phenylarsine oxide or diamide.
      These all sensitized the opening of the non-specific mitochondrial pore to
      [Ca2+], and the effect of tBH was shown to be maintained after washing away the
      tBH, consistent with it being caused by the enhanced CyP binding. The bound CyP
      did not demonstrate peptidyl-prolyl cis-trans isomerase activity. CyP-binding was
      prevented by 5 microM cyclosporin A, but not reversed by cyclosporin treatment of
      the membranes. The effect of tBH on binding was concentration-dependent and
      maximal within 30 s.

PMID- 7522436
TI  - The N-ethylmaleimide-sensitive protein thiol groups necessary for sea-urchin egg
      cortical-granule exocytosis are highly exposed to the medium and are required for
      triggering by Ca2+.
AB  - It is known that sea-urchin egg cortical-granule exocytosis is inhibited by
      agents such as N-ethylmaleimide (NEM) which modify thiol groups. The fusion
      related proteins modified by these agents have yet to be identified, nor is there
      information regarding the topography of these thiol groups. Furthermore, the step
      in cortical-granule exocytosis at which these thiol groups participate is
      unknown. In this study we have investigated the topological properties of, and
      the temporal requirement for the function of, the fusion-related thiol groups by
      treating the isolated exocytotic apparatus with high-molecular-mass dextrans and
      BSA carrying thiol-reactive 3-(2-pyridyldithio)propionate groups. The dextran
      derivatives inhibited exocytosis. The BSA derivative was much less inhibitory.
      Inhibition was reversed by treatment with dithiothreitol. When NEM was added to
      the dextran-derivative-treated exocytotic apparatus, treatment with
      dithiothreitol completely reversed inhibition, indicating that the dextran
      derivatives inhibit by reacting at the NEM-sensitive sites. A pulse of Ca2+
      applied in the presence of inhibitors did not trigger any fusion following the
      removal of the inhibitor by dithiothreitol. These data show that the thiol
      groups, the modification of which by NEM inhibits exocytosis, are exposed to the
      medium in terms of their accessibility to macromolecules. They also show that the
      fusion-related thiol groups are required during the Ca(2+)-dependent stage of
      exocytosis.

PMID- 7522438
TI  - Post-translational processing of the inter-alpha-trypsin inhibitor in the human
      hepatoma HepG2 cell line.
AB  - In human hepatoma HepG2 cells, the serum inter-alpha-trypsin inhibitor (ITI)-like
      protein is synthesized from two protein precursors, the heavy chain (H) H2 and
      the light chain (L). Both of them carry sulphate groups involved in the
      chondroitin sulphate glycosaminoglycan (GAG) linkage, as demonstrated by
      [35S]sulphate labelling, chondroitinase digestion and inhibition with beta-D
      xyloside, an artificial GAG acceptor. While inhibition of N-glycosylation
      prevented neither the maturation nor the secretion of the ITI-related entities,
      brefeldin A induced the accumulation of H and L precursors in the cells,
      therefore blocking subsequent association and maturation of the precursors before
      their secretion. The enzyme system involved in the ester linkage between H and L
      chains is localized in the trans-Golgi network since no ITI-like protein could be
      obtained in the presence of monensin; instead free heavy-chain protein forms and
      bikunin were secreted in culture supernatants. The ITI-like protein synthesized
      by HepG2 cells is therefore composed of two heavy chains HC2 linked to two
      bikunin chains by chondroitin sulphate bridges, although the GAG linkage between
      HC2 chains is presumably different. Further, a different maturation route leading
      to restricted heavy-chain forms, Hm and Hd, could be shown.

PMID- 7522437
TI  - Regulation of splicing is responsible for the expression of the muscle-specific
      2a isoform of the sarco/endoplasmic-reticulum Ca(2+)-ATPase.
AB  - Tissue-specific alternative processing of sarco/endoplasmic reticulum Ca(2+)
      ATPase 2 (SERCA2) transcripts generates functionally different Ca2+ pump isoforms
      in muscle compared with non-muscle tissues. In non-muscle cells, the SERCA2 pre
      mRNA can be polyadenylated at a site located between the donor and acceptor
      splice site of an intron which is only removed in muscle tissues. To define the
      cis-active elements involved in differential processing, we constructed a
      minigene (pCM beta SERCA2) containing the 3' end of the SERCA2 gene. When stably
      transfected into a myogenic cell line, minigene transcripts were differentially
      processed depending on the differentiation state of the cells. This proves that
      the essential elements required for regulated processing are present in the
      construct. Furthermore, co-transfection of the pCM beta SERCA2 minigene and a
      myogenin expression vector in a fibroblast cell line induced muscle-specific
      splicing of transcripts from pCM beta SERCA2. This shows that trans-acting
      factor(s) responsible for muscle-specific processing can be induced by one of the
      important regulatory genes of muscle differentiation. Inactivation of the non
      muscle poly(A) site did not induce splicing in non-muscle cells. This excludes a
      simple competition model between splicing and polyadenylation, but it is
      consistent with splicing being very inefficient in non-muscle cells. Moreover,
      splicing could be induced in non-muscle cells by optimizing the muscle-specific
      donor splice site and/or by shortening the intron length. We therefore propose
      that expression of the muscle-specific SERCA2a isoform is the result of
      activation of an otherwise inefficient splicing process.

PMID- 7522441
TI  - Association of the GPI-anchored leucocyte surface glycoproteins with ganglioside
      GM3.
AB  - The major glycolipid co-immunopurifying with the glycosylphosphatidylinositol
      anchored leucocyte surface glycoprotein CD59 from detergent lysates of human T
      cell lines HPB ALL, Jurkat and myeloid line HL-60 was identified as the
      glycosphingolipid GM3. Monoclonal antibodies to GM3 immunoprecipitated the same
      large detergent-resistant, protein-tyrosine kinase containing "GPI-complexes" as
      antibodies to several GPI-anchored proteins. Therefore GM3 is another component
      of these large membrane complexes potentially involved in signalling through GPI
      anchored receptors or through some glycolipids.

PMID- 7522439
TI  - Biphasic effect of estrogen on neuronal constitutive nitric oxide synthase via
      Ca(2+)-calmodulin dependent mechanism.
AB  - Estrogen is known to retard the development of atherosclerosis and to work in the
      brain, but the mechanism of hormonal action is completely unknown. We
      investigated the effect of estrogen on the activity of neuronal constitutive
      nitric oxide synthase (NNOS). A low concentration of estrogen (10(-10)(-7) M)
      enhanced the activity of homogenates of the cytosol fraction of rabbit
      cerebellums and also that of partially purified NNOS, and high dose (10(-6)(-5)
      M) attenuated them. The study using estrogen receptor antagonists, tamoxifen,
      clomiphene, and ICI182780 suggested that estrogen receptor did not relate
      significantly to those effects of 17 beta-estradiol. 17 alpha-estradiol or
      progesterone did not change significantly it in low doses, although moderately
      inhibited it in high doses. Estrogen enhanced the fluorescence of dansyl
      calmodulin in low doses and attenuated it in high doses, suggesting that estrogen
      affects Ca(2+)-calmodulin directly. This study demonstrated that estrogen has a
      biphasic effect on the activity of NNOS through a Ca(2+)-calmodulin.

PMID- 7522440
TI  - Mast cell activation induces P-selectin-dependent leukocyte rolling and adhesion
      in postcapillary venules in vivo.
AB  - As studied by intravital microscopy, local challenge with the mast cell
      secretagogue compound 48/80 was found to increase the leukocyte rolling fraction,
      decrease rolling velocity and induce firm leukocyte adhesion in postcapillary
      venules of the rat mesentery. These effects of compound 48/80 were inhibited by a
      monoclonal anti-P-selectin antibody, but not by combined treatment with H1 and H2
      histamine-receptor antagonists. Moreover, the response to compound 48/80 was not
      mimicked by exogenous histamine or 5-hydroxytryptamine (5-HT). These novel
      findings indicate that mediator(s) other than histamine and 5-HT evoke P-selectin
      dependent leukocyte rolling and thereby promote firm leukocyte adhesion in mast
      cell-dependent inflammation.

PMID- 7522443
TI  - Involvement of ecto-ATPase as an ATP receptor in the stimulatory effect of
      extracellular ATP on NO release in bovine aorta endothelial cells.
AB  - The secretion of nitric oxide (NO) was stimulated by the addition of ATP or ADP,
      but not by AMP or adenosine, in cultured bovine aorta endothelial cells.
      Inhibitors of ecto-ATPase, NaN3 and Ap5A, significantly inhibited the
      stimulation, while an inhibitor of P2Y-purinoceptor and ecto-ATPase, RB2,
      completely suppressed it. A non-hydrolyzable ATP analogue, AMP-PNP, stimulated NO
      release; the stimulation was completely suppressed by RB2 but not by NaN3 and
      Ap5A. Therefore, only P2Y-purinoceptor was involved in the stimulation by AMP
      PNP, while both ecto-ATPase and P2Y-purinoceptor were involved in the stimulation
      by ATP and ADP. It is not clear whether the stimulation is dependent on the
      dephosphorylation activity of ecto-ATPase or not, but the enzyme appears to act
      as an ATP and ADP receptor for signal transduction through adenine nucleotides.

PMID- 7522442
TI  - Regional expression of epithelial dipeptidyl peptidase IV in the human
      intestines.
AB  - The expression of DPP IV/CD26 was studied in epithelial cells from different
      regions of the human small intestine and colon. The following data were obtained:
      1) DPP IV/CD26 activity was highest in ileum and jejunum, low in duodenum and not
      detectable in colon; 2) The amount of DPP IV, as analyzed by Western blotting,
      was very low in duodenum and increased up to the ileum. No DPP IV protein was
      detected in colon; 3) RT-PCR analysis showed the expected 315-bp product in the
      small intestine with the highest signal in ileum and jejunum and a low signal in
      duodenum; a faint PCR signal could be detected in colon. Similar data were
      obtained by Northern blot analysis which revealed a 3.6-kb transcript only in
      small intestine. It is concluded that DPP IV/CD26 gene expression in human
      intestine is highest in the distal small intestine, and that is regulated at the
      mRNA level.

PMID- 7522444
TI  - A bacterial nitric oxide synthase from a Nocardia species.
AB  - Nitric oxide synthase (EC 1.14.23) was discovered in a Nocardia species. The
      bacterial nitric oxide synthase was purified as much as 380 fold by affinity
      chromatography over 2',5'-ADP-agarose. The partially purified enzyme required
      NADPH, O2, CA++, FAD, FMN, and tetrahydrobiopterin as cofactors in the conversion
      of L-arginine to L-citrulline and nitric oxide. The apparent Km for L-arginine
      was determined to be 8.2 microM, and the Vmax was 840 nmole NADPH consumed/min/mg
      protein. The enzyme was competetively inhibited by NG-nitro-arginine with an
      apparent Ki of 14.6 microM. The experimental evidence provides confirmation of
      the first microbial nitric oxide synthase in microorganisms.

PMID- 7522445
TI  - Lipopolysaccharide primes human basophils for enhanced mediator release:
      requirement for plasma co-factor and CD14.
AB  - Lipopolysaccharide (LPS) is known to enhance IgE-mediated basophil degranulation.
      Recently, the complex of LPS and plasma LPS-binding protein(LBP) has been shown
      to induce secretory response via CD14 in monocytes and neutrophils. In the
      current study, we observed that the sensitivity to LPS of basophils was increased
      to 100-fold by co-incubation with plasma. LPS promptly completed its effect and
      amplified degranulation by stimuli bypassing IgE-receptors. Treatment with anti
      CD14 completely abolished the priming effect of LPS. These results indicate that
      the priming effect of LPS on basophil mediator release is mediated via CD14, and
      that plasma co-factor, possibly identical to LBP, potentiates this reaction.

PMID- 7522446
TI  - Variations in the size and sulfation of heparin modulate the effect of heparin on
      the binding of VEGF165 to its receptors.
AB  - The binding of the 165 amino-acid form of vascular endothelial growth factor
      (VEGF165) to the VEGF receptors of vascular endothelial cells was potentiated by
      heparin and heparan-sulfate, but not by other glycosaminoglycans. Heparin
      fragments of 16-18 sugar units inhibited the binding of 125I-VEGF165 to VEGF
      receptors, while fragments larger than 22 sugar units potentiated the binding.
      Over-sulfated heparin was a better potentiator of 125I-VEGF165 binding than
      native heparin. O-desulfated and N-desulfated heparins potentiated the binding to
      a lesser extent than native heparin. Heparin and N-desulfated heparin efficiently
      inhibited the binding of 125I-VEGF165 to alpha 2-macroglobulin, but surprisingly,
      O-desulfated heparin was an ineffective inhibitor. Since alpha 2-macroglobulin
      does not bind heparin, it follows that VEGF165 does not bind O-desulfated heparin
      efficiently. These results suggest that the mechanism by which heparin modulates
      the binding of VEGF165 to the VEGF receptors may require an interaction with cell
      surface heparin binding molecules.

PMID- 7522447
TI  - Rabbit FKBP-59/HBI does not inhibit calcineurin activity in vitro.
AB  - The effect of recombinant FKBP-59/HBI or of its first N-terminal domain FKBP
      59/HBI-I on the phosphatase activity of calcineurin (a Ca(+2)-calmodulin
      dependent phosphatase) was tested in vitro in the presence or absence of the
      immunosuppressant drug FK506. Contrarily to the inhibition observed with the
      immunosuppressant complex FKBP-12-FK506, no significant inhibition was observed
      with FKBP-59/HBI or FKBP-59/HBI-I in the presence of FK506, even though FKBP
      59/HBI-1 is nearly 55% homologous to the immunophilin FKBP-12. Inhibition was
      tested both with native calcineurin (calcineurin A: Mr 58-59 kDa) and with
      protease activated, calmodulin independent calcineurin (calcineurin A: Mr 45
      kDa). There was no competitive effect of FKBP-59 on the inhibitory activity of
      the FKBP-12-FK506 complex, even when the molar concentration of FKBP-59/HBI was
      100 times higher than that of FKBP-12. Clearly, although the first domain of FKBP
      59/HBI displays several structural and functional features of FKBP-12, it does
      not interact with calcineurin.

PMID- 7522448
TI  - G-CSF induces tyrosine phosphorylation of the JAK2 protein in the human myeloid G
      CSF responsive and proliferative cells, but not in mature neutrophils.
AB  - Granulocyte colony-stimulating factor (G-CSF) stimulates a rapid phosphorylation
      on tyrosines of several proteins of Mr. 130, 100, 90, 70, 44 kd in human myeloid
      leukemia cell line cells, Kasumi-1, which respond to G-CSF to proliferate in
      vitro. In HL60 cells, only a 100 kd protein was phosphorylated, and no detectable
      phosphorylated proteins were observed in neutrophils by the stimulation of G-CSF.
      Among these proteins, the 130 kd protein was immunoprecipitated by anti- JAK2
      serum. While JAK2 is a non receptor tyrosine kinase and is reported to be
      involved in the signal transduction by various cytokines including growth
      hormone, erythropoietin, and granulocyte-macrophage colony-stimulating
      factor/interleukin-3, it is strongly suggested that a signaling pathway that
      relates to the cell proliferation triggered by G-CSF in immature hematopoietic
      cells also involves JAK2.

PMID- 7522449
TI  - [A metaplasic bladder].

PMID- 7522450
TI  - [Feulgen and Rossenbeck staining using a microwave oven for quantification of DNA
      by image analysis].
AB  - A domestic microwave oven was used to modify the Feulgen staining procedure in
      order to speed up the preparation of cytopathologic smears for the quantification
      of cell DNA in image analysis. This simple technique needs some precautions
      concerning the temperature, the hydrolysis time and the position of staining
      dishes inside the oven must be taken in order to get reproducible results.
      Thereafter, the conventional staining time can be reduced to 30%. This technique
      can be applied to cytopathologic smears from various tissues: bladder, prostate,
      breast, ovary.

PMID- 7522452
TI  - Use of computer graphic filters for the nuclear grading of hematoxylin and eosin
      stained specimens from prostatic lesions.
AB  - An inexpensive workstation is being developed to assist pathologists in
      diagnosing routine hematoxylin and eosin-stained slides. A linear discriminant
      model was applied to karyometric features of prostate lesions, and a grade
      according to Mostofi was determined from the discriminant values. Twenty cases,
      five of hyperplasia and five each of carcinoma Mostofi grades I, II and III, for
      a total of 600 nuclei, were selected to train the model. Computer graphic filters
      were constructed from the discriminant values. Each segmented nucleus has a
      colored frame (the graphic filter) displayed around it. The color, determined
      from discriminant values and correlated with the grades, ranges from green for
      hyperplasia, yellow for low grade, orange for medium grade and red for high
      grade. An additional 20 cases, 5 of hyperplasia and 5 each of the Mostofi grades,
      for a total of 538 nuclei, were selected to test the graphic filter. Ninety-six
      percent of the hyperplasia nuclei were framed in green, 84% of low grade nuclei
      were framed in yellow, 90% of medium grade nuclei were framed in orange, and 89%
      of high grade nuclei were framed in red. These results indicate the potential of
      the color graphic filter to show the pathologist immediate and accurate visual
      information about the grade of a nucleus. This method may help with the difficult
      diagnosis of borderline lesions and may help in making the diagnosis from scanty
      biopsy material.

PMID- 7522453
TI  - Prognostic value of quantitatively measured AgNORs in ductal mammary carcinoma.
AB  - Argyrophilic proteins of nucleolar organizer regions (AgNOR proteins) were
      stained by a modified silver staining technique. Paraffin sections from 137 cases
      of invasive ductal carcinoma of the breast were investigated. The nuclei and
      AgNOR dots were quantitatively measured by means of a semiautomatic image
      analysis system. Follow-up data for about 120 months (mean, 102 +/- 47) and
      clinical/histologic and DNA distribution parameters were available for all
      patients. The prognostic significance of AgNOR parameters was tested by Cox
      regression analysis. Four AgNOR features showed a significant univariate
      correlation with survival time. In multivariate analysis offering all the
      available parameters, one AgNOR parameter (coefficient of variation of relative
      AgNOR area) ranked at the third position beyond the standard deviation of DNA
      distribution and pTNM/staging. When considering the distant recurrence-free
      survival of patients, the same AgNOR feature provided significant additional
      prognostic information. Performing survival analysis for the prognostically
      defined subgroup of pTNM/stage I patients and offering all DNA and AgNOR features
      the same AgNOR parameter yielded the highest prognostic validity. These results
      show that quantitatively measured AgNORs yield prognostic factors in breast
      cancer.

PMID- 7522451
TI  - Inhibition of cell growth and intracellular Ca2+ mobilization in human brain
      tumor cells by Ca2+ channel antagonists.
AB  - The effects of various Ca2+ channel agonists and antagonists on tumor cell growth
      were investigated using U-373 MG human astrocytoma and SK-N-MC human
      neuroblastoma cell lines. Classical Ca2+ channel antagonists, verapamil,
      nifedipine, and diltiazem, and inorganic Ca2+ channel antagonists, Ni2+ and Co2+,
      inhibited growth of these tumor cells in a dose-dependent manner. Except Ni2+,
      these Ca2+ channel antagonists did not induce a significant cytotoxicity,
      suggesting that the growth-inhibitory effects of these drugs may be the result of
      the influence on the proliferative signaling mechanisms of these tumor cells. In
      contrast, Bay K-8644, a Ca2+ channel agonist, neither enhanced the growth of
      tumor cells nor increased intracellular Ca2+ concentration, indicating that
      voltage-sensitive Ca2+ channels may not be involved in tumor cell proliferation.
      Moreover, growth-inhibitory concentrations of Ca2+ channel antagonists
      significantly blocked agonist (carbachol or serum)-induced intracellular Ca2+
      mobilization, which was monitored using Fura-2 fluorescence technique. These
      results suggest that the inhibition of the growth of human brain tumor cells
      induced by Ca2+ channel antagonists may not be the result of interaction with
      Ca2+ channels, but may be the result of the interference with agonist-induced
      intracellular Ca2+ mobilization, which is an important proliferative signaling
      mechanism.

PMID- 7522455
TI  - Congestion, air pollution, and road fatalities in urban areas.
AB  - The continuous rapid growth in vehicle miles travelled coupled with the rapid
      increase in traffic congestion on highways of virtually every large urban area,
      explain a major portion of the observed deterioration of urban air quality. To
      halt this deterioration and to secure safe and healthy environments and improve
      the quality of life in our cities, it is useful to initiate and implement
      programs that treat jointly traffic congestion, air quality, and road safety.
      Market-based strategies, driven by price mechanisms, have been proposed as the
      best and most efficient way to decrease traffic congestion and to reduce vehicle
      emission. Congestion pricing, emission fees, reducing emissions of high-polluting
      vehicles, and introducing more efficient vehicle and/or fuel technologies are not
      mutually exclusive strategies and therefore they can be employed jointly within
      an overall strategy. In view of the conflicting objectives that may exist between
      improving urban air quality and reducing road fatalities and traffic congestion,
      it is of great importance to investigate thoroughly these functional
      relationships. The results of such studies will help decision makers identify the
      "socially optimal level of congestion" that will yield the highest net social
      benefit.

PMID- 7522456
TI  - Antibodies to the collagen-like region of C1q and type II collagen are
      independent non-cross-reactive populations in systemic lupus erythematosus and
      rheumatoid arthritis.
AB  - The collagen-like region (CLR) of the first component of complement, C1q, and
      type II collagen are structurally similar, raising the possibility of epitopes in
      common, and of the existence of autoantibodies that are cross-reactive.
      Accordingly, antibodies to the CLR of C1q and to type II collagen were measured
      in patients' sera with systemic lupus erythematosus (SLE) and rheumatoid
      arthritis (RA) by an ELISA. IgG antibodies to the CLR of C1q were present in 17%
      of patients with SLE but none with RA, and IgA antibodies were present in 10% and
      8% of patients with SLE and RA, respectively. IgG antibodies to type II collagen
      were present in 15% and 25% of patients with SLE and RA, respectively, and IgA
      antibodies in 15% and 28% of patients with SLE and RA, respectively. There was no
      correlation in either disease between the serum levels of antibodies to the CLR
      of C1q and antibodies to type II collagen. For sera with antibodies to both
      antigens, neither competitive inhibition by ELISA nor preabsorption with the
      alternative antigen affected the level of reactivity to the other antigen. Thus
      antibodies to the CLR of C1q and antibodies to type II collagen are independent
      and non-cross-reactive populations, and presumably occur by different types of
      immunogenic stimulation.

PMID- 7522454
TI  - Problems concerning the quality of DNA measurements on Feulgen-stained imprints.
      A study of five fixation techniques.
AB  - Feulgen-stained rat liver imprints were investigated, and hepatocytes,
      lymphocytes and granulocytes were measured. Additionally, chicken erythrocytes
      placed on the slides were measured as an external DNA standard. The imprints were
      treated according to five different fixation protocols. The measured integrated
      optical density (IOD) was normalized according to the leukocytes and afterwards
      scaled according to the diploid hepatocytes. The mean IOD, coefficient of
      variation (CV), standard error of the mean (SEM) and IOD ratios of distinct cell
      groups were calculated. The CV of the IOD for hepatocytes was slightly better for
      air-dried preparations. It was larger for leukocytes than for hepatocytes and
      worst for chicken erythrocytes. The SEM of hepatocytes did not show remarkable
      differences between the fixation groups; in general it was near 1%. In all cases
      the IOD ratios of 2c, 4c and 8c hepatocytes reasonably well followed the expected
      ratio of 1:2:4 except for wet, formalin-fixed hepatocytes (3.8). The ratios of
      leukocytes to 2c hepatocytes were about 1.0 for air-dried preparations but
      considerably lower (0.85) for wet fixation in formalin. The IOD ratios of chicken
      erythrocytes to 2C hepatocytes varied from 0.33 to 0.35. The deviation of the
      ratios of single specimens from the estimated mean of a fixation group are
      described.

PMID- 7522457
TI  - The association of primary biliary cirrhosis and systemic sclerosis is not
      accounted for by cross reactivity between mitochondrial and centromere antigens.
AB  - A proportion of patients with primary biliary cirrhosis (PBC) develop the CREST
      variant of systemic sclerosis (SSc) and in these individuals antimitochondrial
      antibodies (AMA) and anticentromere antibodies (ACA) coexist. Immunological cross
      reactivity between mitochondrial and centromere-associated antigens might account
      for the clinical and serological overlap between these conditions. Therefore,
      antibodies were affinity purified from the 70 kD polypeptide corresponding to the
      E2 component of the pyruvate dehydrogenase complex (PDHC) and from CENP-C, a 140
      kD centromere-associated protein, to examine this possibility. Although the
      purified antibodies reacted with their corresponding antigens, no evidence of
      shared determinants between the 70 kD protein and CENP-C could be detected
      whether the antibodies were prepared from monospecific sera or from sera
      containing both AMA and ACA. Therefore, AMA and ACA present discrete autoantibody
      populations which may coexist in the same patient and may influence the clinical
      picture but have both structural and immunologically independent antigenic
      targets.

PMID- 7522458
TI  - Cytoskeletal neurofilament gene expression in brain tissue from Alzheimer's
      disease patients. I. Decrease in NF-L and NF-M message.
AB  - The cytoskeletal changes seen in brains of patients with Alzheimer's disease
      include neurofibrillary tangles, neuritic plaques, Hirano bodies, and
      granulovacuolar degeneration. Northern and slot blot analyses were used to
      investigate the expression of the genes coding for actin, tubulin,
      neurofilaments, and histone in brain tissue from Alzheimer's disease patients and
      normal aged controls. We found a marked decrease of 94% in the expression of the
      neurofilament gene coding for the medium size subunit (150 kDa) and a 73%
      decrease in the expression of the gene coding for the small subunit (68 kDa) in
      Alzheimer's disease patients as compared to controls. Expression of the other
      genes, such as actin and histone, did not show any significant difference.
      Expression of the gene coding for medium size, neurofilament gene was not
      decreased in other neurodegenerative diseases, such as amyotrophic lateral
      sclerosis and Parkinson's disease. This abnormality in neurofilament gene
      expression may explain some of the pathologic features found in Alzheimer's
      disease patients.

PMID- 7522459
TI  - Epitopic heterogeneity of human 3 beta-hydroxysteroid dehydrogenase in villous
      and extravillous human trophoblast.
AB  - A new monoclonal antibody (FDO26G) is described which was raised against purified
      human 3 beta-hydroxysteroid dehydrogenase type I (3 beta-HSD type I). FDO26G
      reacted strongly with villous syncytiotrophoblast, weakly with some trophoblast
      cells in chorion laeve, and not at all with extravillous trophoblast in
      cytotrophoblast cell islands and decidual trophoblast. All these types of
      trophoblast reacted strongly with monoclonal antibody FDO161G, which has
      previously been shown to react with 3 beta-HSD type I and, like FDO26G, reacts
      strongly with adrenal cells. Mapping experiments using a combination of lacZ
      fusion polypeptides and synthetic peptides located the FDO26G epitope to residues
      354-366 at the C-terminal end of the molecule, a sequence that is identical in
      the type I and type II forms of the enzyme. The epitope contains a consensus for
      a casein kinase-II site with serine 359 as the candidate phosphorylation site.
      This suggested that the lack of reactivity of FDO26G to 3 beta-HSD in
      extravillous trophoblast might be due to phosphorylation at serine 359. Peptide
      354-366 was synthesized with phosphoserine at residue 359 and its binding to
      FDO26G was compared with that of the unphosphorylated peptide. FDO26G bound the
      phosphopeptide at least as strongly as the unphosphorylated peptide. It is
      concluded that the lack of staining of extravillous trophoblast by FDO26G is due
      to the presence of a different sequence at residues 354-366 and that a hitherto
      unidentified third isoform of human 3 beta-HSD is expressed in these cells.

PMID- 7522460
TI  - Translocation of protein kinase C isozymes in lactotroph-enriched rat anterior
      pituitary cell cultures: differential effects of substance P and phorbol ester.
AB  - Translocation of protein kinase C (PKC) from the cytosol to the plasma membranes
      is believed to reflect activation of the enzyme. We have studied translocation of
      PKC in lactotroph-enriched anterior pituitary cell cultures by measuring the
      incorporation of gamma-32P from [gamma-32P]ATP into a synthetic peptide
      substrate, MBP4-14, and by immunoblotting of PKC isozymes. Using cells
      permeabilized with digitonin the effects of PKC cofactors on the distribution of
      the enzyme were studied. Ca2+ (50 nM) and dioctanoyl-sn-glycerol had no effect
      when tested alone, but in combination they caused a redistribution of PKC from
      the soluble to the particulate fraction. Arachidonic acid needed Ca2+ to induce
      translocation of PKC, while being ineffective under Ca(2+)-free conditions.
      Western blot analysis of partly purified PKC from lactotroph-enriched pituitary
      cells revealed the presence of the alpha, beta, delta and zeta isozymes. 12-O
      Tetradecanoylphorbol 13-acetate (TPA) and substance P displayed different
      patterns of redistribution of PKC isozyme immunoreactivity from soluble to
      membrane-attached forms. Thus, TPA induced time- and dose-dependent (mean
      effective concentration (EC50) = 1 nM) translocation of the alpha, beta and delta
      species, while substance P stimulated time- and dose-dependent (EC50 = 1 nM)
      redistribution of the alpha and beta isozymes. zeta subtype immunoreactivity
      could not be translocated by either agonist; neither could the immunoreactivity
      of zeta be down-regulated by long-term treatment (24 h) with TPA. The results
      indicate that simultaneous activation of phospholipases C and A2 induces a
      synergistic activation of PKC. Finally it is suggested that substance P may exert
      some of its effects in lactotrophs by translocation of PKC isozymes alpha and
      beta.

PMID- 7522461
TI  - Transurethral radiotherapy for benign prostatic hypertrophy-related urethral
      obstruction. Dosimetry, ethics, and preliminary results.
AB  - The aim of this study is to present our preliminary experience in treating BPH
      related urine retention, resistant to other medical treatment, with transurethral
      brachytherapy. We also deal with dosimetric analysis so as to eliminate ethical
      concerns about the exposure of patients not suffering from cancer to a certain
      level of body irradiation. Patients suffering from BPH-related urethral
      obstruction were treated with two transurethral applications (three weeks apart)
      of Cs137 MDR, which delivered a total of 16 Gy, at 0.5 cm from the urethral walls
      (dose rate 5-7 Gy/h). The application was done under ultrasonographic
      observation. Dosimetric calculation of the radiation exposure of the human body
      during transurethral radiotherapy (TURT) was performed for patients suffering
      from prostate cancer and treated with external beam radiotherapy and a boost dose
      through transurethral brachytherapy. For this purpose we used TLDs on skin
      surface and dosimetric analysis of X-ray films. Five patients treated for BPH
      urethral obstruction presented no sign of acute toxicity. All of them were weaned
      of their indwelling catheter immediately after the end of the first application.
      Obstruction did not recur within 12-18 months of follow-up. The dose delivered
      outside the prostate ranges from 1-7 cG, depending upon location. Proximal rectal
      and bladder walls received 1-2 Gy, a dose that is far from inducing acute or late
      toxicity. The estimated risk for carcinogenesis is negligible, and the expected
      benefit for the quality of life transcends the risks. No ethical concern is
      justified for testing transurethral radiotherapy for BPH-related urethral
      obstruction. TURT seems to be effective and provides durable results. Further
      investigation is required.

PMID- 7522463
TI  - Interphase chromosomes of Friend-S cells are attached to the matrix structures
      through the centromeric/telomeric regions.
AB  - DNA of the attachment sites of Friend erythroleukemia cells, isolated according
      to the conventional procedure, represents short, nuclease-resistant fragments
      with sizes below 400 bp, belonging to the class of mouse satellite. A number of
      experiments have indicated that their unusual resistance is due to complexing
      with RNA. By various approaches, it was confirmed that similar fragments might be
      recovered from total DNA following extensive digestion with DNase I. In situ
      hybridizations revealed further that at mitosis the sequences of the attachment
      sites are located at the centromeric/telomeric regions of the chromosomes, while
      at interphase they are redistributed into 9-13 well-defined clusters spread
      throughout the entire nuclear area. Parallel biochemical and electronmicroscopic
      studies have clarified, moreover, that the all three compartments of the matrix
      harbor such sequences. Thus, it appears that the attachment sites described
      function only at interphase, anchoring the both ends of each interphase
      chromosome to the matrix structures.

PMID- 7522464
TI  - Efficient second-strand cDNA synthesis using T7 DNA polymerase.
AB  - We present a second-strand cDNA synthesis method that takes advantage of both the
      very high processivity and the very high 3' exonuclease activity of T7 DNA
      polymerase. The first strand is synthesized with reverse transcriptase using
      oligo(dT) as a primer. After alkaline hydrolysis of the mRNA template, a tract of
      dT residues is synthesized with terminal transferase at the 3' end of the first
      strand. The second strand is synthesized using oligo(dA) as a primer. Several
      oligo(dA) molecules probably anneal to the poly(dT) tract. Because the 3'
      exonuclease activity of T7 DNA polymerase is very high, the region of the tract
      annealed to these oligo(dA) molecules is digested. However, the region of the
      tract annealed to the very oligo(dA) molecule used as a primer for second-strand
      synthesis is protected. The resulting cDNA molecules could be cloned with a high
      efficiency. The size distribution of cloned c-myc DNAs was estimated by Southern
      blot analysis of phage DNA prepared from the amplified library and by analysis of
      isolated clones. The results indicate that this method allows to obtain full
      length cDNA clones with a high efficiency.

PMID- 7522462
TI  - Evidence for a p53-independent pathway for upregulation of SDI1/CIP1/WAF1/p21 RNA
      in human cells.
AB  - SDI1 is an inhibitor of DNA synthesis that we isolated by expression screening
      cDNAs prepared from senescent, terminally nondividing human cells. Other groups
      then cloned this gene as a cyclin-dependent kinase (cdk)-interacting protein
      (CIP1, p21) that inhibits cdks; the gene was also isolated by screening for genes
      transactivated by p53 (WAF1). p53 levels are low in senescent and quiescent
      contact-inhibited or serum-deprived normal human cells, which we have found
      express high levels of SDI1 mRNA. This indicates that alternate pathways for
      upregulation of message level of this gene may exist. We therefore proceeded with
      the study presented here, treating human cells with a variety of growth-arrest
      inducing agents, including some that damaged DNA, and found that RNA levels of
      SDI1 were increased in all cases that resulted in growth inhibition. More
      important, with the exception of gamma-radiation, most of these agents were able
      to elevate SDI1 message levels in cells lacking wild-type p53. At least two
      distinct kinetic profiles for RNA induction were observed, one that implicated
      p53 transactivation and occurred early enough to cause arrest, and another that
      clearly was p53 independent and suggested a role for the SDI1 gene product in the
      maintenance rather than in the cause of inhibition of DNA synthesis.

PMID- 7522465
TI  - [Epidemiology of AIDS and tuberculosis].

PMID- 7522466
TI  - CD28-B7 interactions in T-cell activation.
AB  - Previous work has shown that optimal activation of CD4+ T cells requires co
      stimulatory signals in addition to the primary signal provided by the antigen
      receptor. Recent work has demonstrated that CD28 is the primary co-stimulatory
      signal receptor for T cells, and B7 its natural ligand on antigen presenting
      cells. In the past year, it has become clear that the importance of CD28-mediated
      co-stimulatory signals extends to virtually all T-cell subsets. In addition, the
      existence of multiple ligands that are differentially expressed on antigen
      presenting cells has been documented. The picture that is emerging is of a
      complex and dynamic interplay of co-stimulatory molecules on both the T cell and
      the antigen-presenting cell that serves to regulate activation. This offers novel
      approaches to the manipulation of immune responses in vivo.

PMID- 7522467
TI  - Cell-mediated cytotoxic mechanisms.
AB  - There are two competing, but probably really complementary, models for the
      mechanism of cell-mediated cytotoxicity. One depends upon contact-mediated
      transmembrane signaling, and the other on the exocytosis of toxic materials by
      the killer cell. There is exciting news on both fronts. Transmembrane signaling
      has been shown to involve the surface molecule Fas/APO-1 on targets and its
      ligand on cytotoxic T cells. The Fas ligand has been cloned, and is a member of
      the tumor necrosis factor family. The major cytolytic molecule in the exocytosis
      pathway is perforin; perforin knock-out mice have been produced, and they display
      many intriguing abnormalities. It has been a bumper year for cytotoxicologists.

PMID- 7522470
TI  - Tracheal autograft revascularization and transplantation.
AB  - OBJECTIVE: No vascular pedicle can be obtained reasonably to provide
      revascularization of a tracheal graft by direct microvascular suture. This study
      is a morphometric analysis of epithelial regeneration, submucosal
      revascularization, and mucosal thickness of isolated, tracheal segments
      revascularized by a lateral thoracic fascial flap. The purpose of the first part
      of the study is to determine the optimal period of tracheal viability after
      isolation and revascularization. The second part consisted of a reimplantation of
      the revascularized autograft into its original tracheal location. DESIGN: A
      tracheal segment was excised in 30 animals, and the segment was wrapped in the
      lateral thoracic fascia. The segments were reviewed histologically and
      morphometrically 2 to 28 days after graft isolation and after injection of the
      lateral thoracic artery with a blue silicone dye. Twelve grafts were reimplanted.
      Six segments were reinserted in the original direction and six segments were
      reinserted in the opposite direction. Tracheal airway clearance was studied by
      observation of the movement of carbon particles placed at different locations on
      the native and transplanted tracheal mucosa. MEAN OUTCOME MEASURES: Tracheal
      autograft revascularization and reepithelialization. RESULTS: Histologic
      evaluation of the revascularized grafts revealed an optimal viability of the
      autograft 16 to 20 days after isolation. The autografts could be reimplanted
      successfully after this period. This demonstrated the viability of the isolated
      grafts after a revascularization period of 16 days. The original direction of the
      mucosal clearance was preserved after reimplantation. The clearance in the
      opposite direction, with the 180 degrees rotated segments, however, had no
      influence on survival.

PMID- 7522468
TI  - Three-dimensional mammalian cell growth on nonwoven polyester fabric disks.
AB  - Small disks of nonwoven polyester fabric (NWPF), similar to Fibra-Cel carriers,
      were surface treated with strong acid and used as a high surface area support
      matrix for in vitro culture of anchorage dependent MRC-5 cells. The disks can be
      autoclaved, and require inocula concentrations of only 2-5% of the final cell
      densities, which have reached 10(8) cells/mL of disk bed volume. Scanning
      electron microscopy photographs shown herein reveal that cells grow in a
      multilayered fashion between the randomly arrayed fibers of the nonwoven fabric,
      emulating in vivo growth.

PMID- 7522472
TI  - Identification of Carnobacterium spp. and Leuconostoc spp. in meat by genus
      specific 16S rRNA probes.
AB  - Oligonucleotide probes specific for Carnobacterium and Leuconostoc species were
      constructed from the variable regions of 16S rRNA obtained from the literature
      and sequence data bases. The probes were hybridized with crude nucleic acid
      extract from 32 type strains of lactic acid bacteria (LAB) commonly found on
      meat. Two of the probes hybridized only to the four Carnobacterium species
      whereas the other two hybridized only to five of the six Leuconostoc species
      tested. The probes were also hybridized with nucleic acids from unknown strains
      of LAB. The identification was consistent with the results of biochemical tests
      used to characterize the two genera.

PMID- 7522471
TI  - Characterization of a psychrotrophic Clostridium causing spoilage in vacuum
      packed cooked pork: description of Clostridium algidicarnis sp. nov.
AB  - A Clostridium species causing spoilage of vacuum-packed refrigerated pork was
      isolated and characterized. The unknown organism differed phenotypically from
      other clostridial species usually associated with spoilage. Phylogenetic analyses
      based on 16S rRNA gene sequencing demonstrated that the psychrotroph represents a
      distinct line of descent within the genus Clostridium. It is proposed that the
      organism be classified as a new species of the genus Clostridium, Clostridium
      algidicarnis.

PMID- 7522469
TI  - Growth and differentiation of meatal skin grafts in the middle ear of the rat.
AB  - OBJECTIVE: To determine the behavior of epidermal cells after transplantation in
      the middle ear. DESIGN: In a rat model, full-thickness meatal skin grafts were
      transplanted into the middle ear and studied morphologically and
      immunohistochemically with the use of antibodies directed against different
      cytokeratin (Ck) polypeptides, which are markers of different types of epithelial
      cell differentiation. RESULTS: The grafts had either transformed into epithelial
      cysts or had become integrated into the middle ear epithelium. The epithelium of
      the integrated grafts showed gradual transition into the epithelium of the middle
      ear. A clear distinction between epidermal cells and middle ear epithelium could
      be made only on the basis of their Ck profiles. The Ck profiles of the grafts
      revealed a decrease in the expression of epidermal Cks, while nonepidermal Cks
      became expressed. These changes can be ascribed to replacement of the dermal
      mesenchyma by mesenchyma from the middle ear. In two ears with superimposed
      infection, the graft epithelium showed expansive growth. CONCLUSIONS: Meatal
      epidermis is well tolerated in the middle ear, but superimposed infection can
      induce expansive growth. These findings favor the concept that the progressive
      growth of cholesteatoma is related to the presence of inflammatory processes.

PMID- 7522473
TI  - Clonal selection and amplification of phage displayed antibodies by linking
      antigen recognition and phage replication.
AB  - The immune response generates a tremendous array of antibody specificities by VDJ
      gene rearrangements. A similar diversity can be obtained by expressing entire V
      gene repertoires on the surface of filamentous bacteriophages creating large
      antibody libraries. Here we describe how the clonal selection mechanisms of the
      humoral immune response can also be mimicked in the phage display system by
      linking antigen-recognition and phage replication. We have achieved this by
      displaying antibody libraries on engineered, non-infectious phage with gene 3
      deletions. Individual, antigen-specific phage are made replication competent by
      allowing a fusion protein, consisting of the antigen and phage coat protein 3, to
      bind the displayed antibody fragment. This fusion protein bridges the phage and F
      pili of the bacteria and allows infection to be initiated and the phage to be
      clonally amplified with specific enrichment factors of approximately 10(10) after
      only two rounds.

PMID- 7522474
TI  - Extraction of lysozyme, alpha-chymotrypsin, and pepsin into reverse micelles
      formed using an anionic surfactant, isooctane, and water.
AB  - The extraction of lysozyme, alpha-chymotrypsin, and pepsin from buffered salt
      solutions into reverse micelles was examined at different pH values and
      surfactant concentrations. The reverse micelles was formed by mixing aqueous
      buffer supplemented with KCl and an organic phase of isooctane(2,2,4
      trimethylpentane), containing the anionic surfactant, Aerosol O. T. (dioctyl
      ester of sodium sulfosuccinic acid). The technique of dynamic laser scattering
      was used to measure the size of reverse micelles which were in equilibrium with
      the aqueous phase. It was found that the size of the reverse micelles decreased
      with increasing ionic strength but increased with increasing AOT concentration.
      In the process of extraction, the reverse micelles might have rearranged
      themselves to host the protein. The sizes of protein-filled and -unfilled reverse
      micelles were different, and an open equilibrium could be reached between them.
      Under the extraction conditions, only a small number of micelles were found to
      contain protein.

PMID- 7522476
TI  - Epithelial antigens in carcinomas of the ovaries. Relation to histological
      classification.
AB  - In an attempt to assess and improve the histological classification of ovarian
      tumors the value of immunohistochemical techniques has been examined in 50
      ovarian tumors. A panel of six immunohistochemical markers (two cytokeratins,
      EP4, EMA, CEA, and vimentin) seems to have no additional value in differential
      diagnosis and typing of ovarian tumors.

PMID- 7522477
TI  - Purified protein products of rDNA technology expressed in animal cell culture.
AB  - During the past 7 years, 14 versions of 7 rDNA proteins have been licensed which
      are derived from animal cell culture expression systems. These medically useful
      products have included hormones, coagulation factors, enzymes and a vaccine.
      Aspects of the molecular complexity, manufacture, control and utilization of
      these products are discussed. In contrast to previous generations of biological
      production technology, the technology for production of rDNA-derived proteins in
      animal cells appears to be safe.

PMID- 7522479
TI  - Identification of two human sperm populations using flow and image cytometry.
AB  - Flow cytometric studies of human sperm from fertile men display a constant and
      characteristic bimodal nonartifactual DNA pattern confirming the existence of two
      distinct populations. The main population is represented by a peak followed by a
      shoulder ("marginal population"). The appearance of this marginal population
      fluctuates with either freezing and thawing or with Percoll gradient
      centrifugation. We have analyzed both the main and marginal sperm populations by
      flow cytometry after cell sorting, laser scanning cytometry, light microscopic
      evaluation, and their sensitivity to DNase digestion. We have observed that the
      marginal population detected in fertile men represents a sperm group altered in
      the nuclear condensation, yielding unstable chromatin which appears more
      stainable with propidium iodide.

PMID- 7522478
TI  - A correlation of argyrophilic nucleolar organizer regions with prognoses in
      patients with maxillary sinus squamous cell carcinoma.
AB  - Argyrophilic nucleolar organizer regions (AgNORs) were determined by a
      semiautomatic image analyzer in a group of 28 patients with T2 or T3 maxillary
      sinus squamous cell carcinoma. The group was separated into recurrent and non
      recurrent groups, metastatic and non-metastatic groups, as well as groups
      strongly or weakly positive for epidermal growth factor receptor (EGFR). The mean
      number and area of AgNOR dots per nucleus and the mean size of each dot were
      calculated. The mean number and area were significantly greater than those in
      normal cells (P < 0.001), but not in recurrent and non-recurrent groups,
      metastatic and non-metastatic groups and groups separated by EGFR. There was also
      no difference found in the mean sizes of tumor and normal cells. These results
      suggest that AgNOR is related to malignant transformation, but not prognosis.

PMID- 7522475
TI  - Nitric oxide synthase in human placenta.
AB  - Nitric oxide synthase is demonstrated immunohistochemically in the cytosol, on
      granules, and on syncytiotrophoblasts membranes. The enzyme is also detected on
      placental villous stroma cells, and on endothelial cells. The histochemical
      staining method NADPH-diaphorase stains the syncytiotrophoblasts intensely, and
      stroma cells more weakly. Membranes of syncytiotrophoblasts immobilized on
      nitrocellulose paper are also stained by NADPH-diaphorase, and by antisera to
      nitric oxide synthase. Oxidases of sex steroid synthesis do, however, influence
      placental trophoblasts and there are discrepancies in the staining pattern of
      endothelial cells. Caution should therefore be exercised when using NADPH
      diaphorase as a staining method for nitric oxide synthase in placenta.

PMID- 7522480
TI  - Expression of the complement regulatory protein CD59 on human spermatozoa:
      characterization and role in gametic interaction.
AB  - Protectin (CD59) is a complement regulatory protein which blocks the membrane
      attack complex during complement activation. CD59 was identified on the human
      sperm surface by means of H19, an IgG1 anti-protectin mouse monoclonal antibody.
      Using indirect immunofluorescence, flow cytometry and immunoperoxidase, CD59 was
      found to be present on the whole plasma membrane including the head and tail of
      fresh ejaculated, capacitated and acrosome-reacted spermatozoa. Immunoperoxidase
      staining of normal testicular sections indicated that this protein was already
      present on intraluminal germ cells. Analysis of this sperm protein by gel
      electrophoresis and immunoblotting revealed that its molecular weight of 20 kDa
      was comparable to that of CD59 expressed on peripheral blood cells (erythrocytes,
      lymphocytes) and that it was bound to the membrane through a glycophospholipid
      tail which could be released after treatment with phosphatidylinositol-specific
      phospholipase C. Associated to membrane cofactor protein (CD46) and decay
      accelerating factor (CD55) located in the acrosomal membranes, CD59 may
      participate to the protection of male gametes against complement-mediated damage
      as they travel through the female genital tract. Moreover CD59, known as an
      adhesion molecule involved in lymphocyte rosettes, may also participate in cell
      to cell adhesion during gametic interaction since H19 inhibited sperm binding and
      reduced the penetration rate and index during the hamster egg penetration test.

PMID- 7522483
TI  - Novel pore-lining residues in CFTR that govern permeation and open-channel block.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is both a member
      of the ATP-binding cassette superfamily and a Cl(-)-selective ion channel. We
      investigated the permeation pathway of human CFTR with measurements on conduction
      and open-channel blockade by diphenylamine-2-carboxylic acid (DPC). We used site
      directed mutagenesis and oocyte expression to locate residues in transmembrane
      domain (TM) 6 and TM 12 that contact DPC and control rectification and single
      channel conductances. Thus, TM 12 and the previously investigated TM 6 line the
      CFTR pore. In each TM, residues in contact with DPC are separated by two turns of
      an alpha helix. The contributions of TM 6 and TM 12 to DPC block and Cl-
      permeation, however, are not equivalent. The resulting structural model for the
      conduction pathway may guide future studies of permeation in other Cl- channels
      and ATP-binding cassette transporters.

PMID- 7522481
TI  - N-cadherin and Ng-CAM/8D9 are involved serially in the migration of newly
      generated neurons into the adult songbird brain.
AB  - In the adult avian forebrain, neurons continue to be produced in the subependymal
      zone (SZ), from which they migrate upon radial fibers. To identify ligands
      regulating this process, we studied N-cadherin and Ng-CAM/8D9 expression in HVC,
      a neurogenic region of the canary neostriatum. N-cadherin was relatively
      restricted to the SZ and was expressed by dividing, [3H]thymidine-labeled
      precursor cells. However, cellular N-cadherin was down-regulated prior to
      neuronal migration from the SZ. Addition of anti-N-cadherin Fab hastened neuronal
      migration from adult SZ explants, without influencing neuronal number. Unlike N
      cadherin, Ng-CAM/8D9 was expressed by migrating neurons. Anti-8D9 Fab inhibited
      neuronal migration upon cultured ependymoglia, which did not express Ng-CAM/8D9.
      Thus, the departure of new neurons from the adult SZ may require their
      suppression of N-cadherin, whereas their subsequent migration and survival may
      depend upon neuronal expression of Ng-CAM/8D9 and its interaction with a
      heterophilic radial cell receptor.

PMID- 7522484
TI  - A novel role for myelin-associated glycoprotein as an inhibitor of axonal
      regeneration.
AB  - Following nerve injury, axons in the CNS do not normally regenerate. It has been
      shown that CNS myelin inhibits neurite outgrowth, though the nature of the
      molecules responsible for this effect are not known. Here, we demonstrate that
      the myelin-associated glycoprotein (MAG), a transmembrane protein of both CNS and
      PNS myelin, strongly inhibits neurite outgrowth from both developing cerebellar
      and adult dorsal root ganglion (DRG) neurons in vitro. This inhibition is
      reversed by an anti-MAG antibody. In contrast, MAG promotes neurite outgrowth
      from newborn DRG neurons. These results suggest that MAG may be responsible, in
      part, for the lack of CNS nerve regeneration in vivo and may influence, both
      temporally and spatially, regeneration in the PNS.

PMID- 7522482
TI  - A second subunit of the olfactory cyclic nucleotide-gated channel confers high
      sensitivity to cAMP.
AB  - Sensory transduction in olfactory neurons is mediated by intracellular cAMP,
      which directly gates a nonselective cation channel. A cDNA encoding a cyclic
      nucleotide-gated (CNG) ion channel subunit (rOCNC1) has been cloned previously
      from rat olfactory epithelium. However, differences between the functional
      properties of rOCNC1 and the native olfactory CNG channel suggest that the native
      channel could be composed of several distinct subunit types. Here, we report the
      cloning and characterization of a cDNA encoding a second olfactory CNG channel
      subunit (rOCNC2) that is 52% identical to rOCNC1 and that is expressed
      specifically in olfactory sensory neurons. Expression of rOCNC2 alone in Xenopus
      oocytes does not lead to detectable CNG currents. However, coexpression of rOCNC2
      with rOCNC1 results in a CNG conductance that differs from that detected upon
      expression of rOCNC1 alone and more closely resembles the native conductance in
      several respects, including its sensitivity to cAMP. This suggests that the
      native olfactory CNG channel is a hetero-oligomer composed of rOCNC1 and rOCNC2
      subunits.

PMID- 7522487
TI  - Impact of interferon at induction chemotherapy and maintenance treatment for
      multiple myeloma. Preliminary results of a multicenter study by the Italian non
      Hodgkin's Lymphoma Cooperative Study Group (NHLCSG).
AB  - In 1990 the Italian Non-Hodgkin's Lymphoma Cooperative Study Group (NHLSG)
      started a multicenter study on the role of interferon (IFN) in multiple myeloma
      (MM). The schedule of treatment was based on the assumption that melphalan plus
      prednisone (MP) would be better for good-prognosis patients, whereas poor
      prognosis patients would benefit from polychemotherapy. Accordingly, IFN was
      included randomly for the induction treatment of good-prognosis patients and
      randomly as maintenance of the response achieved in both groups. Up to now 78
      patients of the 124 enrolled have completed the induction treatment and are
      evaluable for response and response duration. The overall response rate was 59%.
      Sixty-two percent of good-prognosis patients obtained objective response, 9/14
      (64%) with MP and 9/15 (60%) with MP+IFN. Up to now, with a median follow-up of 9
      months from the evaluation of response, no difference has been recorded between
      the maintenance and no maintenance groups on relapse rate, neither in good- nor
      in poor-prognosis patients.

PMID- 7522485
TI  - Intratracheal instillation of silica up-regulates inducible nitric oxide synthase
      gene expression and increases nitric oxide production in alveolar macrophages and
      neutrophils.
AB  - Alveolar macrophages (AM) exposed to cytokines or bacterial lipopolysaccharide
      (LPS) produce the free radical nitric oxide (NO.) by an inducible nitric oxide
      synthase (iNOS). They also release reactive oxygen free radicals following
      exposure to silica dust. The purpose of the present study was to determine
      whether NO. is produced by rat AM and/or recruited leukocytes following the
      intratracheal (IT) instillation of silica. Male Sprague-Dawley rats (175 to 225
      g) were IT instilled with either silica dust (10 mg/100 g body wt) or LPS (0.25
      mg/100 g body wt). After 24 h, bronchoalveolar lavage cells (BALC) and lavaged
      lung tissue were assayed for iNOS mRNA. Cell counts of BALC and iNOS-dependent (N
      omega-nitro-L-arginine methyl ester [L-NAME]-inhibitable) chemiluminescence
      generated by AM were also determined. Northern blot analysis demonstrated that
      the steady-state levels of BALC iNOS mRNA were significantly increased by 3-fold
      following IT silica and by 7-fold following IT LPS. Partially enriched fractions
      of either AM or leukocytes from silica-treated rats both exhibited significantly
      elevated iNOS mRNA in Northern analysis. iNOS-dependent chemiluminescence was
      significantly increased in AM by 36-fold following IT silica and by 89-fold
      following IT LPS. Differential counts of BALC showed that AM numbers did not
      change in any of the treatments; however, red blood cells increased by 30-fold
      following IT silica and by 23-fold following IT LPS. Total leukocytes
      (polymorphonuclear leukocytes plus lymphocytes) increased by 58-fold following IT
      silica and by 274-fold following IT LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522486
TI  - Oxygen modulates nitric oxide production selectively in fetal pulmonary
      endothelial cells.
AB  - Acute hypoxia causes pulmonary hypertension in the fetus and newborn that is
      contrasted by systemic hypotension or normotension. To better understand the role
      of nitric oxide (NO) in this specific pulmonary vascular response, we determined
      the acute effects of decreased oxygenation on NO production in ovine fetal
      pulmonary and systemic (mesenteric) endothelial cells. NO was assessed by
      measuring cGMP accumulation in fetal vascular smooth muscle (VSM) cells during co
      culture incubations of endothelium and VSM (40 s) in the presence of the
      phosphodiesterase inhibitor isobutylmethylxanthine. Changes in cGMP were
      dependent on the endothelium and on NO synthase and guanylate cyclase activity.
      At high O2 (680 mm Hg), basal NO was detectable and NO increased 6- to 10-fold
      with bradykinin or A23187. In pulmonary endothelium, basal NO fell 58% at pO2 =
      150 mm Hg and 51% at 40 mm Hg versus 680 mm Hg, while NO with bradykinin fell 56%
      and 63%, respectively. NO with A23187, however, was unchanged at 150 mm Hg, but
      it fell 56% at 40 mm Hg. In contrast, in systemic endothelium basal and
      stimulated NO production were not altered at lower O2. Findings were similar
      using pulmonary or systemic detector VSM cells, and exogenous L-arginine had no
      effect. Thus, decreased O2 acutely attenuates NO production specifically in fetal
      pulmonary endothelial cells. This process is not related to changes in O2 or L
      arginine availability as substrates for NO synthase; alternatively, it may be
      partially mediated by specific effects of O2 on pulmonary endothelial cell
      calcium homeostasis.

PMID- 7522489
TI  - Analysis of molecular recognition: steric electrostatic and hydrophobic
      complementarity.
AB  - We discuss three important aspects of molecular recognition: steric,
      electrostatic and hydrophobic. Steric fit means that interacting atoms may not
      approach each other beyond their van der Waals radii and, simultaneously,
      crevices should be filled as densely as possible. Electrostatic fit requires the
      maximum ionic and polar (hydrogen bond or other) interaction between host and
      guest atoms while the hydrophobic fit corresponds to the association trend
      between apolar groups in an aqueous medium. Space-filling models, obtained by
      molecular graphics, illustrate steric complementarity while we use molecular
      electrostatic potentials (MEPs) and fields (MEFs) to investigate electrostatic
      and hydrophobic matching. Molecular regions with negative and positive MEPs
      attract and repel a positive probe charge, respectively, so we consider them as
      attracting each other. Furthermore we postulate that regions with MEFs of similar
      magnitude tend to associate more strongly than those with very different fields
      (similis simili gaudet principle). We apply the above rules to the study of
      complementarity in the trypsin-BPTI complex and in a crystalline association
      between styrene epoxide as guest and a camphor-based anthracene derivative as
      host. We discuss molecular similarity on the same footing as complementarity and
      give some examples on the application of the concept to the rationalization of
      relative strengths of trypsin inhibitors.

PMID- 7522490
TI  - Application of molecular genetics in public health: improved follow-up in a
      neonatal hemoglobinopathy screening program.
AB  - Newborn screening for the hemoglobinopathies has been shown to reduce morbidity
      and mortality, particularly for sickle cell anemia, by facilitating initiation of
      penicillin prophylaxis by 4 months of age. The purpose of the current
      investigation was to determine whether molecular genetic follow-up testing could
      be introduced into a neonatal hemoglobinopathy screening program and, if
      successfully introduced, whether it would reduce time to diagnostic confirmation.
      Between July 1, 1991, and October 7, 1992, 518 original dried blood specimens
      were referred from the Texas Department of Health Neonatal Hemoglobinopathy
      Screening Program for molecular genetic follow-up testing. Allele-specific
      cleavage (ASC) after amplification with matched and mismatched polymerase chain
      reaction primers was compared to allele-specific oligonucleotide (ASO)
      hybridization. By November 2, 1992, molecular genetic analyses were definitive in
      506, and agreement was observed between ASC and ASO hybridization in all
      specimens analyzed. Approximately 13% of those initially screened FS were
      considered probable S/beta-thal by DNA and RNA testing. Rapid molecular genetic
      analysis contributed to a substantial reduction of the mean age at confirmation
      by approximately 50%, to about 2 months of age. ASC is a reliable method for
      molecular genetic analysis of dried blood specimens, providing methodology which
      can be readily automated. An automated method is demonstrated that is based on
      microtiter plate technology and will significantly reduce labor intensity and
      costs, while increasing sample throughput. Even with current manual testing
      methods, DNA and RNA analysis of initial newborn screening specimens will reduce
      the age at confirmation well under 4 months, the age cut-off for effective
      initiation of penicillin prophylaxis.

PMID- 7522488
TI  - Interferon treatment of neuroendocrine tumour xenografts as monitored by MRI.
AB  - The neuroendocrine-differentiated colonic carcinoma cell line (LCC-18) was
      transplanted to 29 nude mice (Balb/c). The purpose of the present study was to
      establish an animal model that would allow monitoring with magnetic resonance
      imaging (MRI) of changes induced by interferon (IFN) therapy and to evaluate
      whether the therapeutic response, as expressed by changes in MR signal
      characteristics and tumour proliferation activity, could be modulated by
      different IFN dosages. IFN did not seem to have any obvious antiproliferative
      effect on the LCC-18 tumour cell line transplanted to nude mice and no convincing
      treatment-related changes in rho values or T1 and T2 relaxation values were
      observed. The animal model was probably unsuitable for demonstration of IFN
      effects.

PMID- 7522491
TI  - Optimization of subtractive hybridization in construction of subtractive cDNA
      libraries.
AB  - The efficiency of subtraction, integrity of residual single-stranded cDNA, and
      efficient recovery of nanogram quantities of double-stranded cDNA are the three
      most important factors affecting quality of subtractive hybridization reactions
      prior to subtractive cDNA library construction. Techniques for efficient
      isolation of single-stranded cDNA, after subtraction, have greatly improved from
      early protocols based on hydroxylapatite chromatography to phenol-chloroform
      extraction of biotin-streptavidin-crosslinked polynucleotides or oligo(dA)
      cellulose affinity chromatography. Factors affecting mRNA stability at the
      hybridization step, however, also have consequences that directly affect the
      complexity of the library and the length of cDNAs recovered. We have optimized
      the subtractive hybridization step in subtractive cDNA library construction to
      ensure that single-stranded cDNAs survive hybridization as near to full length as
      possible. These improvements have enabled successful construction of subtractive
      cDNA libraries from the nanogram quantities of single-stranded cDNA remaining
      after extensive liquid hybridization to high calculated C(o)t values.

PMID- 7522492
TI  - Influence of lindane and paraquat on oxidative stress-related parameters of
      erythrocytes in vitro.
AB  - 1. The influence of lindane and paraquat on oxidative stress-related parameters
      of the red blood cell was studied in vitro. 2. Lindane addition did not modify
      either the t-butyl hydroperoxide-induced oxygen uptake of the erythrocytes and
      the induction time preceding it, or the activity of catalase, superoxide
      dismutase, glutathione peroxidase and glucose 6-phosphate dehydrogenase, in
      conditions of comparable levels of haemoglobin and methaemoglobin. 3. Red blood
      cells exposed to paraquat exhibited a concentration-dependent decrease in the t
      butyl hydroperoxide-induced oxygen consumption and increments in either the
      induction period or in the activity of catalase and glucose 6-phosphate
      dehydrogenase, with no changes in superoxide dismutase activity and a small
      decrement in that of glutathione peroxidase. 4. These data indicate that lindane
      does not interfere with the oxidant status of the erythrocyte, while paraquat
      addition leads to an increment in the anti-oxidant capacity of the red blood
      cell.

PMID- 7522493
TI  - V3 region polymorphisms in HIV-1 from Brazil: prevalence of subtype B strains
      divergent from North American/European prototype and detection of subtype F.
AB  - Viral DNA sequences were determined over the V3 region of env from 28 infected
      individuals living in the high HIV-1 prevalence Brazilian cities of Rio de
      Janeiro and Sao Paulo. Twenty-six belonged to envelope sequence subtype B,
      prevalent in North America and Europe, and one was classified as subtype F, found
      recently in Brazil and in Romania (one appeared to be a B/F recombinant).
      Octameric sequences at the tip of the subtype B V3 loops were variable and
      distinct from those prevalent in North America and Europe. The GPGR motif,
      prevalent in North American/European strains, was found in only 8 (28.5%)
      sequences, whereas GWGR was found in 12 (43%) and novel sequences in 8 (28.5%).
      Brazilian subtype B sequences also diverged from the consensus North
      American/European strains over the remainder of the V3 loop. These results
      suggest that Brazilian HIV-1 B strains may have important antigenic differences
      from prototype subtype B strains currently being evaluated for use in HIV
      vaccines. These results should be taken into account for future vaccine programs
      in Brazil.

PMID- 7522495
TI  - Expression of epitopes of the tumour-associated glycoprotein 72 and
      clinicopathological correlations in mammary carcinomas.
AB  - We analysed the immunohistochemical expression pattern of the distinct
      carbohydrate epitopes of the TAG-72 molecule, defined by the monoclonal
      antibodies (MAbs) B72.3, CC-49 and CC-83, in 92 breast carcinomas of different
      histological type, and in other histological components identified in the mammary
      tissue samples studied. The results were correlated with the clinico-pathological
      characteristics of the tumours, and with their proliferative activity, assessed
      by thymidine labelling index (TLI). Expression of the TAG-72 epitopes was
      detected in all the tumour histotypes analysed, but patterns of immunoreactivity
      tended to vary in relation to type and level of differentiation. The comparative
      analysis of the reactivities of the three anti-TAG-72 MAbs revealed differences
      in their ability to recognise neoplastic lesions. MAb CC-49 reacted with the
      highest percentage of tumours (82%), and also tended to yield the highest
      percentages of immunoreactive cancer cells, while B72.3 and CC-83 reacted with
      lower percentages of tumours (respectively, 55 and 51%), and identified lower
      percentages of immunoreactive cells. High levels of expression of the three TAG
      72 epitopes were detected in areas of in situ ductal carcinoma. Comparatively
      lower levels of immunohistochemical positivity were found in atypical epithelial
      hyperplasia, normal mammary epithelium and epithelium with cystic disease. TAG-72
      epitope expression was correlated with prognostic parameters. The synchronous
      expression of the three epitopes significantly correlated with large tumour size
      (> 2 cm), and with high histological grade. No correlations could be demonstrated
      between TAG-72 phenotypes and nuclear grade, lymph node status and proliferative
      activity (high versus low).

PMID- 7522496
TI  - EWS/FLI-1 rearrangement in small round cell sarcomas of bone and soft tissue
      detected by reverse transcriptase polymerase chain reaction amplification.
AB  - Recent cloning of the t(11;22) region has led to the detection of a number of
      sequences involved in the breakpoints by substituting a sequence which encodes a
      putative RNA binding domain for that of the DNA binding domain of the human
      homologue of murine FLI-1. Several tumours display consistent translocation at
      t(11;22) (q24;q12), a finding that suggests these fusion transcripts could be
      expressed and detected by reverse transcriptase polymerase chain reaction
      amplification. To date, only a small number of Ewing's sarcomas (Es) and
      peripheral neuroectodermal tumours (pPNET) of bone have been tested with this
      novel molecular biology approach. In this study, we confirmed the presence of the
      three putative chimaeric transcripts on 7 cases of Es and pPNET sarcomas of bone
      and soft tissue, providing 100% positivity for the tested tumours. For
      comparative purposes, a number of other neuroectodermal tumours were analysed
      with negative results: esthesioneuroblastoma, retinoblastoma, Schwannoma. A
      primitive soft tissue sarcoma (ectomesenchymoma) with a 22 chromosome
      rearrangement did not express any transcript, nor did a number of non
      neuroectodermal small round cell sarcomas of soft tissue (rhabdomyosarcomas) and
      bone (microcellular osteosarcoma), conventional bone sarcomas, leiomyosarcomas,
      malignant fibrous histiocytomas and synovial sarcomas. These results reinforce
      the value of molecular biology techniques for the correct assessment of histology
      difficult evaluable neoplasms, such as the group of small round cell tumours
      within the Es family.

PMID- 7522499
TI  - Carcinoid syndrome and anaesthesia.

PMID- 7522497
TI  - [Self-expanding metallic endoprostheses in the palliative treatment of biliary
      obstructions in nonresectable carcinoma of the head of the pancreas].
AB  - OBJECTIVE: A study of immediate and long-term results with the self-expandable
      metallic stent (Wallstent), in the treatment of biliary obstruction in 25
      patients with non resectable carcinoma of the head of the pancreas was carried
      out. Stent placement was successful in all patients. RESULTS: Complication rate
      was 4% (n = 1); one patient had venous bleeding after percutaneous catheter
      placement. There was no procedure related mortality (30-day mortality); hospital
      stay was 6, 7 days (2-12). Average survival was 6 months (+/- 2.97). Average
      patency of the initial stent lasted 5 months (+/- 2.01); comfort index was 83%.
      Five patients required re-admission. Late complications were cholangitis in 2 and
      stent occlusion in 4. Disimpaction in one patient and placement of additional
      stent (PAL-MAZ) in the remaining 3 patients were performed. One patient required
      surgical treatment; hepaticojejunostomy was performed. Elapse time between
      prostheses placement and stent occlusion was 3.4 months (2-4.5). CONCLUSIONS: We
      conclude that metallic stent placement has low morbidity without mortality and
      provide good quality of live. The most frequent late complication was prostheses
      obstruction.

PMID- 7522498
TI  - Influence of halothane on the effect of cAMP-dependent and cAMP-independent
      positive inotropic agents in human myocardium.
AB  - Volatile anaesthetics have a variety of effects on the myocardium, namely a
      negative inotropic effect and a catecholamine sensitizing effect. The present
      study was designed to see if the hydrocarbon anaesthetics interact specifically
      with subcellular targets of the myocardial cell, by examining the effects of
      halothane in the presence of positive inotropic agents with different mechanisms
      of action. Experiments were performed in isolated electrically driven left
      ventricular preparations (1 Hz, 37 degrees C, Ca2+ 1.8 mmol litre-1) from human
      hearts obtained at cardiac surgery. The concentration-response curves of
      noradrenaline, milrinone, BayK 8644 and Ca2+ were investigated in the absence and
      in the presence of halothane. Halothane enhanced the efficacy of noradrenaline
      and milrinone but not of Ca2+ or BayK 8644. The potency of milrinone was also
      increased by halothane, whereas the potency of BayK 8644 was decreased and those
      of noradrenaline and Ca2+ were unchanged. Halothane differentially influences the
      effects of agents with different positive inotropic mechanisms. This experimental
      approach can be taken as a functional method to localize the mechanisms of action
      of the inhalation anaesthetics in human myocardium, namely sensitization of cAMP
      formation and interaction with L-type Ca2+ channels.

PMID- 7522494
TI  - Reactions of Ugandan antisera with peptides encoded by V3 loop epitopes of human
      immunodeficiency virus type 1.
AB  - The specificities of antibodies reacting with peptides encoded by V3 loop apical
      epitopes were determined for sera from 230 seropositive Ugandans, including
      asymptomatic persons and AIDS patients, sampled between 1986 and 1992. Most (71%)
      of the sera reacted with the peptide encoded by HIV-MN, 59% reacted with a
      peptide containing a consensus sequence for Ugandan variants of the HIV-1 global
      subtype A (referred to as the Uganda A consensus), 59% reacted with a peptide
      containing a consensus sequence for Ugandan variants of the global subtype D (the
      Uganda D consensus); 19% of the sera also reacted with peptides encoded by the
      divergent Ugandan variant U31. There was no obvious correlation between the
      specificities of antibody binding and the V3 loop sequence of the corresponding
      virus isolate or provirus. Competitive inhibition and antibody adsorption
      experiments indicated that the MN peptide, the Uganda A consensus peptide, the
      Uganda D consensus peptide, and the U31 peptide were recognized by different sets
      of antibodies. Eighteen percent of the sera from AIDS patients and 26% of the
      sera from asymptomatic persons were monospecific for one of the MN, Uganda A, or
      Uganda D peptides. Whereas all except one of the singly reactive AIDS sera were
      specific for MN, 39% of the singly reactive asymptomatic sera were specific for
      MN, 39% for the Uganda A peptide, and 21% for the Uganda D peptides. We conclude
      that analysis of the specificities of antibodies against the V3 loop epitopes in
      sera from asymptomatic persons could provide useful epidemiological data about
      the prevalence of viral subtypes within a population.

PMID- 7522500
TI  - [Mast cell mediator release after endobronchial challenge with adenosine 5'
      monophosphate in asthmatic subjects].
AB  - Mediator release from activated mast cells is also likely to take place in the
      asthmatic airways in vivo during adenosine-induced bronchoconstriction. To test
      this hypothesis, we evaluated mast cell mediator release directly into the
      airways of 9 asthmatic subjects after endobronchial challenge with adenosine by
      bronchoalveolar lavage (BAL). The mediators measured were histamine, tryptase,
      and PGD2. When compared to the saline-challenged segment, the response to AMP
      instillation was characterized by a prompt reduction in airway calibre paralleled
      by a significant 4.2-fold increase in PGD2 levels in the BAL fluid (p = 0.004).
      There were also increases in median histamine (from 200.1 to 433.6 pg/mL) and
      tryptase levels (from 0.31 to 0.46 ng/mL) recovered after AMP challenge, although
      they were not significant. These findings support the view that acute
      bronchospastic response to AMP in asthmatic airways is paralleled by the local
      release of mast cells derived products, particularly PGD2.

PMID- 7522501
TI  - [Role of the vascular component in growth of solid tumors: a historical review].
AB  - Angiogenesis is a fundamental biological process by which new capillary blood
      vessels are formed. It is essential in many physiological conditions, such as
      embryonic development, ovulation and wound repair, and pathological ones, such as
      arthritis, diabetic retinopathy, and tumours. Solid tumours have angiogenesis
      capacity, and tumour growth and metastasis are angiogenesis-dependent. Neoplastic
      cell populations can grow to form a clinically evident tumour only if the host
      produces a vascular network sufficient to sustain tumour growth. Furthermore, the
      new blood vessels provide a gateway for tumour cells to enter the circulation and
      metastasize to distant sites. Tumour angiogenesis is essentially mediated by
      angiogenic molecules elaborated by tumour cells. We review here the most
      important literature on this topic and emphasize the crucial and paradigmatic
      role of this biological process and its relevance in a possible anti-angiogenic
      therapeutic approach to the treatment of solid tumours.

PMID- 7522502
TI  - The structural complexities of the myelin basic protein gene from mouse are also
      present in shark.
AB  - The Golli-mbp gene complex contains two overlapping transcription units with two
      distinct promoters, of which the downstream (myelin basic protein [mbp]) promoter
      is more frequently used. A previous comparison of the downstream promoter
      sequences from shark and mouse allowed the identification of two DNA sequences
      called the boxes I and II and the wobble zone. The boxes I and II sequence is a
      composite cis-acting motif that is thought to be involved in the regulation of
      the downstream promoter. It contains sequences similar to T-antigen, MyoD/E2A,
      and glucocorticoid receptor-binding sites. The wobble zone codes for an exon (5a
      in the nomenclature of Campagnoni et al., 1993) that is included in messenger
      RNAs transcribed from the upstream promoter. The polypeptides encoded by this
      exon from shark and mouse are 86 and 84 amino acids long, respectively. These
      polypeptides are overall 59% identical and include a region (residues 41-75 in
      shark and 39-73 in mouse) that is 89% identical between the two species. A
      primary sequence analysis showed that each of these polypeptides contains an N
      glycosylation site, phosphorylation sites for Ca2+/calmodulin-dependent protein
      kinase, protein kinase C and casein kinase II, and partial ATP- and GTP-binding
      sites. The shark polypeptide also contains a phosphorylation site for proline
      directed protein kinase. These observations are consistent with the notion that
      the intricate structure and regulation of the Golli-mbp gene complex arose during
      vertebrate evolution within a common ancestor to sharks and mammals.

PMID- 7522504
TI  - Clinical status of the new cytoprotective agent, amifostine.
AB  - In summary, the data presented and reviewed at this symposium provide a strong
      rationale for the use of amifostine as a cytoprotective agent. Amifostine has
      been shown to reduce morbidity in cancer patients receiving radiation and
      chemotherapy without compromising the antineoplastic activity of the cancer
      therapies employed. Amifostine has been investigated extensively and appears
      particularly effective with cisplatin and cyclophosphamide, which operate via
      direct binding to the active species of these alkylating agents. It may also have
      a role in the protection of normal hematopoietic stem cells during bone marrow
      purging prior to bone marrow transplantation. Finally, amifostine may act
      synergistically with hematopoietic growth factors (ie, G-CSF) to protect and
      accelerate the recovery of hematopoietic stem cells exposed to high doses of
      radiation.

PMID- 7522505
TI  - Endothelin excretion during ketoacidosis does not correlate with tubular
      dysfunction.
AB  - Urinary excretion of endothelin was measured by radioimmunoassay in children with
      diabetes mellitus during severe ketoacidosis and 12 days later when blood pH and
      blood glucose concentrations were normal. Metabolically stable diabetic children
      served as controls. Results from apparently healthy children without diabetes
      mellitus were used as normal values. Renal tubular injury was evaluated by the
      urinary excretion of the proximal tubular marker alpha 1-microglobulin and the
      distal tubular marker Tamm-Horsfall protein (THP). During ketoacidosis we
      detected a decreased glomerular filtration rate associated with highly
      significant changes in the excretion of alpha 1-microglobulin, indicating
      proximal tubular damage, and THP, suggesting disturbance of cells of the
      ascending loop of Henle. The daily excretion of endothelin was unaltered but the
      ratio of endothelin/creatinine or endothelin excretion/creatinine clearance were
      significantly enhanced. In conclusion, we could demonstrate that, despite a
      proximal and distal tubular cell dysfunction, endothelin excretion is not
      elevated during ketoacidosis. The increased endothelin excretion when related to
      creatinine clearance may be a consequence of disturbed proximal tubular function
      or dysfunction of the renal medulla.

PMID- 7522503
TI  - PKC gamma gene expression is delayed in postnatal central nervous system of mi/mi
      mice.
AB  - In the central nervous system (CNS), the expression of protein kinase C (PKC)
      genes is strictly controlled by the developmental stage. We have examined the
      expression of PKC genes (cPKC alpha, beta, gamma, and nPKC delta, epsilon) in the
      process of the postnatal development in normal (+/+) C57BL/6 and microphthalmic
      (mi/mi) C57BL/6 mouse brains by Northern blotting and in situ hybridization. By
      Northern blotting, the expression level of cPKC gamma mRNA in mi/mi mice was
      significantly lower than that in +/+ littermates at d 9, 13, and 17. By in situ
      hybridization analysis, cPKC gamma mRNA-positive cells were detected in
      hippocampal and Purkinje cells in +/+ and mi/mi mice, but the magnitude of the
      signals in mi/mi mice was lower than that of +/+ mice, and the number of positive
      cells was smaller, whereas other isozymes (cPKC alpha, beta, and nPKC delta,
      epsilon) showed no significant difference between normal and mi/mi mice. The
      neuronal morphometric analysis by anti-P400 antibody revealed the same number and
      expression level of P400 protein in cerebellar Purkinje cells compared with +/+
      mice. These results indicate that the deficiency of mi gene product causes the
      delayed expression of the cPKC gamma gene.

PMID- 7522506
TI  - Cancer education in Viet Nam: a need for foreign input.
AB  - In Viet Nam cancer education has a low priority because of political and social
      factors. Knowledge about cancer staging and basic management principles is
      stagnated by restricted communication with foreign colleagues and by limitations
      of available techniques. Participation in either formal residency programs or
      conferences for continuing education outside Viet Nam is restricted to select
      individuals of high rank. Most foreign experience is gained from Russia or from
      the former Eastern-bloc nations. Available foreign textbooks and journals are
      limited to those published more than 20 years ago. Infectious diseases are the
      most significant health problem in Viet Nam and they indirectly contribute to the
      incidence of cancer, including the occurrence of hepatocellular carcinoma. A
      widespread epidemic of acquired immune deficiency syndrome (AIDS), acquired both
      outside and within the medical system, is another potential consequence of
      current health care practices. The need for an international exchange of
      scientific knowledge is dramatically reinforced through the identification of
      significant deficits in available medical care and the patterns of mortality in
      this restricted society.

PMID- 7522508
TI  - In-office cancer-screening education of primary care physicians.
AB  - In a demonstration project, education representatives were trained to perform
      "academic detailing" of cancer control information for physicians and for staff
      members of family physicians' offices. One-hour visits were arranged at specific
      times so as to avoid disruption of patient care activities. The representatives
      led discussions of salient tissues regarding early detection of cancer at three
      sites (breast, colon-rectum, and prostate) and left relevant patient education
      materials. Seventeen visits were made to 11 practices involving 22 physicians and
      85 staff members. Ten items were selected as evidence of favorable cancer control
      activities: ashtrays had been removed from the waiting room, patient information
      was displayed in a wall rack, medical records contained a method for prompting
      the physician about preventive or screening services that were due to be
      performed, a recall system reminded patients of services that were due to be
      performed, the receptionist was involved, the nurse was involved, American Cancer
      Society (ACS)-recommended services were used or had been added, the physician
      talked to other physicians about the visit discussions, services or materials had
      been requested from the local ACS unit, and staff members or physicians had
      volunteered to serve the ACS. The compliance rate was 35% at baseline. At post
      intervention assessment, the compliance rate had increased by 35%, for a final
      compliance rate of 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522507
TI  - The use of videotaped lectures in surgical oncology fellowship education.
AB  - A video library of surgical oncology topics was initiated in 1991 as an
      educational forum for fellows in a surgical oncology training program. First-year
      and second-year fellows presented formal medical lectures on specific surgical
      oncology topics that were based on a comprehensive literature review. An abstract
      of the discussion, a list of references, and a copy of the presented slides were
      submitted at the time of presentation of each lecture. The lectures were
      videotaped in front of an audience made up of faculty and fellows of the
      Department of Surgical Oncology, The videotapes were subsequently edited to
      incorporate the presented slides, and these versions were shown separately to
      allow critique of presentation style and content by the faculty and the fellows
      within the Department. Nineteen videotaped presentations from academic years 1991
      1992 and 1992-1993 were evaluated. These videotaped lectures are an informational
      resource, and, of equal importance, they provide an assessible record for self
      analysis of lecturing technique and effectiveness.

PMID- 7522510
TI  - Dacarbazine (DTIC)-based chemotherapy or chemoimmunotherapy of patients with
      disseminated malignant melanoma.
AB  - Combinations of dacarbazine (DTIC) and other cytotoxic agents or alpha-interferon
      were given to 136 patients in five different regimens. The total response rate
      was 32% (95% confidence interval 24-40%); 13% had a complete remission. Female
      patients had a significantly higher chance of response than male patients: 46% vs
      23%. There was also a difference in complete response rate: 25% vs 9%. The
      overall survival was 6 months; 8% of patients had a response of more than 6
      months and 2% of more than 2 years. Although response rates vary among the
      various regimens described in the literature, the complete response rates are
      quite similar and the long-term disease-free survival of these combinations may
      be similar to that of dacarbazine alone.

PMID- 7522511
TI  - Soluble c-erbB-2 fragment in serum correlates with disease stage and predicts for
      shortened survival in patients with early-stage and advanced breast cancer.
AB  - Seventy-nine patients with advanced breast cancer were tested for the presence,
      in serum, of a 110 kDa soluble, c-erbB-2 fragment. Thirty-nine patients were
      seropositive. There was no correlation between seropositivity and menopausal
      status, or with oestrogen status. In addition, no correlation could be found
      between tissue c-erbB-2 immunostaining for the external domain of the c-erbB-2
      receptor and the presence of soluble c-erbB-2 in serum. The presence of serum
      soluble c-erbB-2, however, had a significant impact on survival of patients with
      advanced disease, suggesting that this test may become a useful independent
      prognostic indicator.

PMID- 7522513
TI  - Keratinocyte differentiation in psoriatic scalp: morphology and expression of
      epithelial keratins.
AB  - The morphology of hair follicles was examined in psoriatic scalp biopsies and
      compared with normal scalp. In scalp psoriasis the lower outer root sheath and
      hair matrix were not affected by the psoriatic changes, although there was an
      irregular expansion in the proximal lower outer root sheath. This area has been
      characterized, by the presence of keratin K19-containing cells, as the putative
      stem cell region. In addition, marked shrinkage of the sebaceous glands was seen
      in the psoriatic scalp, as previously reported. A panel of monospecific
      monoclonal antibodies to individual epithelial keratins was used to analyse scalp
      specimens immunohistochemically. Keratin expression in scalp was generally
      unaffected by psoriasis, except for widespread expression of suprabasal keratins
      K16 and K17 in suprabasal interfollicular psoriatic scalp epidermis. Simple
      epithelial keratins K8 and K18 were not found in follicular epithelium from
      either normal or psoriatic scalp, using multiple monospecific antibodies. This
      study shows that keratin K17 is induced suprabasally during epidermal
      hyperproliferation, and cannot therefore be considered a hair follicle-specific
      keratin.

PMID- 7522509
TI  - Cisplatin resistance in mouse fibrosarcoma cells after low-dose irradiation in
      vitro and in vivo.
AB  - Murine fibrosarcoma cells (SSK) exhibit a transient cisplatin resistance after
      low-dose irradiation (5 x 2 Gy) in vitro and in vivo. When resistance is lost, it
      can be restored by a single drug exposure which, without preirradiation, does not
      generate cisplatin resistance in parental cells. There is no cross-resistance to
      radiation. Metallothioneins, which are associated with cisplatin resistance after
      high-dose irradiation (15 x 6 Gy), do not correlate with induction and loss of
      cisplatin resistance after low-dose irradiation. Since cisplatin survival curves
      are also monotonous when drug resistance diminishes, an adaptive response is more
      likely than a mutational event to underlie cisplatin-induced resistance. Drug
      resistance can be overcome by combined exposure to cisplatin in the presence of
      the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Under these
      conditions, cisplatin sensitivity is increased 2.4- to 2.8-fold in the resistant
      strains compared with only 1.5- to 1.8-fold in the parental cells. The cellular
      platinum content with and without IBMX treatment is not significantly different
      in sensitive and resistant cells. Loss of drug resistance correlates with a
      decrease in cisplatin sensitisation by IBMX. This suggests that cisplatin
      resistance after low-dose irradiation may be associated with alterations of the
      cAMP-dependent signal transduction pathway.

PMID- 7522512
TI  - Neuropeptide and neuronal marker studies in vitiligo.
AB  - Neuropeptide and neuronal marker immunoreactivity was studied in skin biopsies
      from lesional and marginal areas in 12 patients with vitiligo, and in seven
      normal controls. The vitiligo was active in seven, static in two, and of unknown
      activity in three. Antibodies against general neuronal marker PGP 9.5 (PGP 9.5),
      substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal
      polypeptide (VIP), and neuropeptide Y (NPY), were used. The epidermis, dermo
      epidermal junction, papillary and reticular dermis, and appendages, were assessed
      semiquantitatively for reactivity with each antibody. Staining with PGP 9.5 in
      the upper dermis was assessed quantitatively by image analysis. An increase in
      reactivity against NPY antibody was seen in five of 10 cases (three with active
      vitiligo) in the marginal areas, and in three of 12 subjects (all with active
      vitiligo) in the lesional vitiligo areas. VIP antibody reactivity showed a
      minimal increase in the marginal and lesional vitiligo areas (in two cases each,
      both of whom had active vitiligo). SP and CGRP reactivities did not differ from
      normal. PGP 9.5 staining was minimally increased at the dermo-epidermal junction
      and lower Malpighian layer in biopsies from marginal areas in three of 10
      subjects (all with active vitiligo). Quantitative analysis of PGP 9.5 reactivity
      in the upper dermis showed no difference between vitiligo and normal biopsies.
      These findings support the concept of neuronal or neuropeptide involvement in
      vitiligo, and in particular suggest that NPY may have a role in the pathogenesis
      of the disease.

PMID- 7522514
TI  - Morphoea lesions are associated with aberrant expression of membrane cofactor
      protein and decay accelerating factor in vascular endothelium.
AB  - One of the main features of systemic and localized forms of scleroderma is
      vascular damage, the mechanism of which is not yet understood. Recently, we have
      shown undetectable or decreased expression of complement regulatory molecules,
      membrane cofactor protein (MCP) and decay-accelerating factor (DAF), in cutaneous
      endothelium of patients with systemic sclerosis (SSc). In some patients, CD59
      expression in endothelium was also altered. As these molecules protect
      endothelial cells from damage by autologous complement, their decreased
      expression could be part of the mechanism of vascular damage in SSc. In the
      present study, we investigated the expression of MCP, DAF and CD59 in the
      endothelium of lesional and non-lesional skin of patients with localized
      morphoea. Normal skin and lesional skin from patients with systemic lupus
      erythematosus, and three inflammatory diseases, were included as relevant
      controls. The results showed that the extent of expression of the three molecules
      in non-lesional skin of patients with morphoea, on all the skin cells and
      structures, was identical to that of normal skin. In lesional skin, however, the
      expression of MCP and DAF in endothelium was either undetectable or only present
      to a very slight degree. CD59 expression in endothelium in lesional skin was
      normal. No such aberrant expression was observed in the lesions of any of the
      control diseases. These results indicate a decreased ability of endothelial cells
      in lesional areas to protect themselves from autologous complement, and this
      could contribute to vascular damage in morphoea lesions.

PMID- 7522515
TI  - Ultraviolet-A radiation induces adhesion molecule expression on human dermal
      microvascular endothelial cells.
AB  - Ultraviolet radiation is capable of inducing numerous skin reactions.
      Considerable amounts of UVA radiation penetrate the epidermis and reach the
      microvascular endothelium of the papillary dermis. In order to investigate
      putative direct effects of UV radiation on endothelial cells, we studied adhesion
      molecule expression by immunostaining procedures and FACS analysis, following
      irradiation of normal human skin and cultured human dermal endothelial cells.
      Enhanced immunostaining for ICAM-1 and E-selectin was detected in biopsies taken
      after in vivo UVA and UVB irradiation, compared with non-irradiated control skin.
      On cultured human dermal endothelial cells, however, ICAM-1 and E-selectin were
      inducible by UVA but not UVB. The induction was dose-dependent, peaking at 20
      J/cm2 for both adhesion molecules, and time-dependent, peaking after 6 and 24 h
      for E-selectin and ICAM-1, respectively. Expression of VCAM-1 and
      PECAM/EndoCAM/CD31 was unaffected by any UV-radiation modality. The functional
      integrity of irradiated cells was monitored by an exclusion assay of the
      fluorescent dye 7-AAD, and by staining for the cytoskeletal proteins actin and
      vimentin. Our results demonstrate that dermal microvascular endothelial cells are
      a critical and direct target of UVA, and suggest they may play a pivotal role in
      UV-induced inflammatory skin conditions.

PMID- 7522517
TI  - Successful treatment of hydroxyethyl starch-induced pruritus with topical
      capsaicin.
AB  - We report a case of recalcitrant pruritus after infusion therapy with
      hydroxyethyl starch (HES) for sudden deafness. The diagnosis was confirmed by
      detection of typical HES storage vacuoles within dermal macrophages and
      perineural cells. Treatment with antihistamines and antipruritic agents, UVB
      irradiation, and neuroleptic drugs, was ineffective. Topical capsaicin (0.05%)
      twice daily produced excellent symptomatic relief, without side-effects.

PMID- 7522518
TI  - Stem cell factor enhances the growth of primitive erythroid progenitors to a
      greater extent than interleukin-3 in patients with aplastic anaemia.
AB  - We examined the combined effects of stem cell factor (SCF), or interleukin-3 (IL
      3) with erythropoietin on the development of haemopoietic progenitors in 19
      patients with aplastic anaemia (AA) and eight normal controls by using an in
      vitro clonal assay. SCF significantly enhanced the growth of total erythroid
      colonies (erythroid bursts, mixed colonies) in 11 patients and all normal
      controls, whereas IL-3 did so in only three patients. The number of SCF- or IL-3
      dependent erythroid colonies was substantially lower in AA patients than in the
      controls. Comparison of the capacity of SCF and IL-3 to increase total erythroid
      colony growth indicated that half of the AA patients responded more strongly to
      SCF than the normal controls, while few patients responded in such a manner to IL
      3. These findings suggest that SCF in vivo will have a more dramatic effect than
      IL-3 in improving anaemia in patients with AA.

PMID- 7522520
TI  - Autoantibodies directed against the epidermal growth factor-like domains of
      thrombomodulin inhibit protein C activation in vitro.
AB  - No consensus has been obtained about the question whether autoantibodies, in
      particular antiphospholipid antibodies (aPL), may cause thrombosis by inhibiting
      thrombomodulin (TM) mediated protein C activation. In order to clarify the
      mechanism by which autoantibodies inhibit TM-mediated protein C activation, we
      have screened 12 patients with autoimmune diseases for the presence of
      circulating autoantibodies inhibiting TM function. In a cross-sectional study we
      found that IgG fractions from two patients (who were aPL negative) inhibited TM
      mediated protein C activation in an assay system using purified components. A
      longitudinal study of six patients with a history of thrombosis of which two were
      aPL positive showed that all had at some time circulating antibodies inhibiting
      TM function, suggesting that the presence of these antibodies is transient. Three
      different TMs were used to identify the epitope of the antithrombomodulin
      antibodies (aTM): rabbit TM, which contains the entire TM molecule; Solulin,
      which contains the extracellular part of TM, and rEGF-TM, which contains the six
      epidermal growth factor (EGF) domains of TM. We showed that the aTM inhibited
      protein C activation mediated by all three TMs, indicating that the aTM are
      directed against the region containing the EGF domains. When TM was incorporated
      in phospholipid vesicles, no inhibition by these aTM could be demonstrated. In
      addition, protein C activation mediated by cultured endothelial cells (EC) could
      not be inhibited by aTM. The lack of inhibition of TM in phospholipid vesicles
      and EC-TM by a TM suggests that aTM only inhibit soluble TM. In conclusion, we
      demonstrated the transient presence of circulating autoantibodies directed
      against the region of TM containing the EGF domains in SLE patients with a
      history of thrombotic complications. We postulate that the presence of antibodies
      to soluble TM may be, in addition to aPL, a risk factor for the occurrence of
      thrombosis in patients with autoimmune diseases.

PMID- 7522519
TI  - Cytokine mRNA expression of bone marrow stromal cells from patients with aplastic
      anaemia and myelodysplastic syndrome.
AB  - We studied mRNA expression of the cytokine granulocyte-colony stimulating factor
      (G-CSF), interleukin-1 beta (IL-1 beta), IL-6, IL-8 and stem cell factor of
      stromal cells derived from bone marrows of nine normal volunteers, eight patients
      with aplastic anaemia (AA) and seven patients with myelodysplastic syndrome
      (MDS). The proportion of endothelial cells, macrophages, fibroblast-like cells
      and adipocytes in stromal cells showed no differences between normal volunteers
      and the patients. Levels of cytokine mRNA expression were determined by reverse
      transcription-polymerase chain reaction. Spontaneous expression occurred and this
      was augmented by LPS stimulation in cells of all the normal volunteers and in
      most patients. When stimulated by LPS, the mean G-CSF and IL-1 beta mRNA
      expressions in patients with AA were significantly higher than normal volunteers,
      but there was one patient showing lower IL-1 beta, IL-6 and IL-8 expression with
      no response to LPS. LPS-induced IL-6 and IL-8 expression of two patients with MDS
      were significantly higher than normal. The spontaneous and LPS-induced protein
      concentration of G-CSF, IL-6 and IL-8 in culture supernatants from 15, 10 and
      four patients, correlated well with the mRNA expression. The correlation
      coefficients were 0 x 92, 0 x 78 and 0 x 91, respectively. In conclusion, there
      were a few patients whose aetiology appeared to be reduction of stromal cytokine
      expression in AA, but most patients with AA and MDS expressed normal or high
      levels of cytokine mRNA.

PMID- 7522516
TI  - Adhesion molecule expression and the inflammatory cell infiltrate in delayed
      pressure urticaria.
AB  - We have investigated the kinetics of the leucocyte infiltrate in delayed pressure
      urticaria (DPU) in relation to the in vivo expression of the cytokine-regulated
      cell surface adhesion molecules, E-selectin (endothelial adhesion molecule-1,
      ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion
      molecule-1 (VCAM-1). Immunohistochemical analysis was performed on biopsies taken
      from unchallenged skin, and at 0, 2, 6, 24, 48 and 120 h after weighted rods had
      been applied to 13 patients with DPU. There was moderate to marked upregulation
      of E-selectin at 6 and 24 h after application of pressure. At 24 h, more patients
      showed expression of VCAM-1 on perivascular cells than before pressure. Moderate
      expression of ICAM-1 was present in some biopsies from both unchallenged and
      pressure-challenged skin, but there was no clear trend. In DPU, there was a
      significant increase in the neutrophil count at 2 h after a pressure challenge,
      with further increases at 6 and 24 h. The median cell counts per high-power field
      of eosinophils and monocyte/macrophages increased significantly at 24 h after
      pressure. Biopsies from four normal controls subjected to an identical pressure
      challenge showed no detectable changes in adhesion molecule expression or in the
      cell infiltrate. The findings in four patients with chronic idiopathic urticaria
      not associated with DPU were qualitatively similar to (but intermediate in
      severity between) the findings in DPU weals at 6 and 24 h. These results suggest
      that vascular endothelial activation is an early response to pressure challenge
      in DPU, and is also present in chronic idiopathic urticaria.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7522521
TI  - Two classes of platelet?

PMID- 7522522
TI  - Cytokine activity after allogeneic bone marrow transplantation. V. Analysis of IL
      2 and IFN production by isolated CD4+ and CD8+ cells.
AB  - Previous studies from this laboratory have shown that PBMC from recipients of an
      HLA-identical sibling bone marrow transplant produce levels of IL-2 which are 10
      100-fold lower than those produced by the same number of PBMC from healthy
      controls, whereas production of IFN-gamma is normal. The present study examined
      IL-2 and IFN production over a range of cell numbers for PBMC and for isolated
      CD4+ and CD8+ cells for controls and marrow transplant recipients. There was a 5
      fold lower IL-2 production in marrow transplant recipient CD8+ cells compared
      with equivalent numbers of control cells, whereas no difference was found in IL-2
      production by CD4+ cells. In contrast, IFN production by CD4+ cells from marrow
      transplant recipients was 4-fold higher than in controls, whereas CD8+ cells from
      both populations produced similar amounts of IFN. When the observed production of
      cytokine by PBMC was compared with the expected production based on the CD4+ and
      CD8+ content of the PBMC, control values were similar, but the expected values
      for both cytokines were approximately 2-fold higher than the observed values for
      marrow transplant recipients. The results suggest that the capacity of T cells
      from marrow transplant recipients to produce IL-2 and IFN is not impaired, but
      that the frequency of cytokine-producing cells may be reduced, and that a
      negative interaction present in recipient PBMC, eliminated by isolating T-cell
      subsets, is responsible for the observed low levels of cytokine production.

PMID- 7522523
TI  - Possible factors influencing the haemoglobin and fetal haemoglobin levels in
      patients with beta-thalassaemia due to a homozygosity for the IVS-I-6 (T-->C)
      mutation.
AB  - We have collected haematological, haemoglobin (Hb) and DNA sequence data for 29
      patients with a homozygosity for the IVS-I-6 (T-->C) mutation with the intention
      of identifying factors contributing to the observed variability in the severity
      of the disease. None of the patients had received blood transfusion therapy for
      at least 6 months prior to the study. Hb levels varied from 5.0 to 9.9 g/dl.
      Patients with high Hb F (more than 1.5 g/dl or > 20%) had high total Hb levels
      (7.5-9.7 g/dl) but some with low Hb F also had high total Hb levels; two had a
      concomitant alpha-thalassaemia-2 (alpha-thal-2) heterozygosity. An inverse
      correlation between the Hb F and Hb A2 levels was observed. The majority of the
      patients were homozygous for haplotype VI (49/58 chromosomes) but haplotypes IV
      (2/58) and VII (7/58) were also present. The only haplotype IV homozygote had
      high Hb F levels with high G gamma values and the C-->T mutation at position -158
      in the G gamma promoter, while both high and low Hb F levels were observed among
      patients with haplotypes VI and VII. Analysis of sequence variations in
      regulatory regions included the 5' hypersensitive sites (HS) 4. 3 and 2 of the
      locus control region (LCR), the G gamma and A gamma 5' flanking regions, the
      second intervening sequence (IVS-II), and the 5' beta-globin gene region in two
      patients with high Hb F (one homozygote each for haplotypes VI and IV), and in
      two patients with low Hb F levels (one homozygote each for haplotypes VI and
      VII). Haplotype specific differences were observed in the LCR 5' HS-2 and in the
      G gamma and A gamma flanking and IVS-II regions; however, no differences were
      present between the low and high Hb F-producing haplotype VI chromosomes,
      suggesting a major role for factors which are not linked to the beta-globin gene
      cluster in mediating gamma-globin gene expression in patients with this type of
      beta-thal.

PMID- 7522524
TI  - Granulocyte colony-stimulating factor inhibits the endogenous leukotriene
      production in tumour patients.
AB  - Granulocyte colony-stimulating factor (G-CSF) is virtually devoid of inflammatory
      side-effects when given to patients in therapeutic doses. This is in contrast to
      other haemopoietic cytokines such as granulocyte-macrophage colony-stimulating
      factor (GM-CSF) or interleukin-3 (IL-3) which may promote inflammatory reactions
      by increasing the number and/or activity of monocytes, eosinophils, mast cells
      and basophils. Inflammatory reactions to GM-CSF and IL-3 appear to be related to
      an increased formation of leukotrienes, known as potent mediators of allergy and
      inflammation. Here we report that, in contrast to GM-CSF or IL-3, G-CSF has the
      potential to inhibit the leukotriene production in vivo. G-CSF may thus act as an
      anti-inflammatory agent. The differential effects of G-CSF and other
      haemopoietins on endogenous leukotrienes may be of major clinical significance.

PMID- 7522525
TI  - SLe(x) expression of normal CD34 positive bone marrow haemopoietic progenitor
      cells.
AB  - We investigated sialylated Lewis x (sLe(x)) antigen expression on CD34 positive
      (CD34+) haemopoietic progenitors in the bone marrow of eight healthy volunteers
      using monoclonal antibodies. We found that in all the samples examined, CD34+
      bone marrow progenitors strongly expressed the sLe(x) antigen. This contradicts
      previous publications which reported sLe(x) expression on malignant blast cells
      but not on normal CD34+ progenitor cells.

PMID- 7522526
TI  - Comparative effects of a highly specific protein kinase C inhibitor, calphostin C
      and calmodulin inhibitors on angiotensin-stimulated aldosterone secretion.
AB  - We have examined the relative roles of the calcium-calmodulin system and protein
      kinase C in angiotensin-mediated aldosterone secretion. We used a highly specific
      protein kinase C inhibitor, calphostin C and two well-accepted calmodulin
      inhibitors, W-7 and calmidazolium. Although both types of inhibitors affected
      angiotensin-induced aldosterone secretion, as judged by the inhibitory doses of
      these compounds, angiotensin-evoked aldosterone secretion was more sensitive to
      calmodulin inhibition than protein kinase C inhibition. Manipulation of
      OFFracellular calcium by dantrolene and thapsigargin also modified aldosterone
      secretion significantly.

PMID- 7522527
TI  - Randomized comparison of cisplatin, methotrexate, bleomycin and vincristine
      (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in recurrent
      or metastatic squamous cell carcinoma of the head and neck. A phase III study of
      the EORTC Head and Neck Cancer Cooperative Group.
AB  - BACKGROUND: The EORTC Head and Neck Cancer Cooperative Group conducted a
      randomized comparison of cisplatin, methotrexate, bleomycin and vincristine
      (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in
      chemotherapy naive patients with recurrent or metastatic squamous cell carcinoma
      of the head and neck. The primary objectives of this study were to investigate
      whether the CF regimen was in anyway superior to the CABO regimen and to detect
      any superiority of these two combinations over cisplatin alone. PATIENTS AND
      METHODS: Three hundred eighty-two patients were randomized to one of three
      treatments: (1) methotrexate (40 mg/m2) days 1 and 15, bleomycin (10 mg) and
      vincristine (2 mg) days 1, 8 and 15, cisplatin (50 mg/m2) day 4, repeated every
      21 days, (2) cisplatin (100 mg/m2) and 5-FU (1 g/m2 x 4), repeated every 21 days,
      and (3) cisplatin (50 mg/m2) days 1 and 8, repeated every 28 days. After 3
      cycles, all responding and stable disease patients in the three arms of the study
      continued with cisplatin alone. RESULTS: The overall response rates to CABO (34%)
      and CF (31%) were superior to C (15%) (p < 0.001, p = 0.003, respectively). In
      addition, complete response rate to CABO (9.5%) was superior to that of C (2.5%)
      (p = 0.02), and also superior to that of CF (1.7%) (p = 0.01). Response was
      associated with performance status and prior treatment, but by multivariate
      analysis treatment type was the important determinant of response (p = 0.0006).
      Although CABO and CF were superior to C with respect to time to progression
      within the first 6 to 8 months after randomization, there was no overall
      difference in progression-free survival or survival between the three arms of the
      study. Both hematologic and non-hematologic toxicity were worse in the
      combination chemotherapy arms. CONCLUSION: We conclude that the CF regimen has no
      advantage over the CABO regimen, which in fact showed a higher complete response
      rate. Both combinations showed improved response rates but also more toxicity and
      no improvement in overall survival in comparison with cisplatin alone.

PMID- 7522529
TI  - Measurement of serum thyrotropin levels using sensitive immunoradiometricassays
      in patients with chronic renal failure: alterations suggesting an intact
      pituitary thyroid axis.
AB  - Serum thyroid stimulating hormone (TSH) levels were measured in 127 patients with
      varying grade of chronic renal failure (CRF). Sensitive immunoradiometricassays
      (IRMA) were used so that small changes in TSH levels if any, could be
      appreciated, and to see if such alterations exhibit some relationship with those
      in thyroid hormone levels. Mean serum TSH levels in the patient group of 2.33
      microU/ml (0.07-7.3) was significantly higher in comparison to 1.73 microU/ml
      (0.25-4.6) in normal subjects (p < 0.001). However, they were not significantly
      different when measured by radioimmunoassay (RIA) as compared to normals. Serum
      triiodothyronine (T3), thyroxine (T4) and free triiodothyronine (FT3) levels of
      72 +/- 32 ng/dl, 7.4 +/- 2.6 micrograms/dl and 2.9 +/- 0.9 pg/ml were
      significantly lower than in normal subjects, whereas serum free thyroxine (FT4)
      showed a slight though not significant elevation. When patients were divided in
      three subgroups according to the degree of renal insufficiency, TSH levels showed
      a gradual rise with corresponding depression in their T3, FT3 and T4 levels. In
      19 patients who were on hemodialysis (HD) and subsequently received successful
      renal transplantation, most of the thyroid function parameters returned towards
      the normals with TSH undergoing significant depression from their pretransplant
      levels as well as from normal levels. The results indicated that a slight but
      significant elevation in TSH levels could be revealed by sensitive IRMA in
      patients with CRF. Rising TSH levels with increasing renal insufficiency and its
      inverse relationship with T3 and T4 levels suggest maintenance of pituitary
      thyroid axis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522528
TI  - Recent advances in hepatic transplantation at the University of Pittsburgh.
AB  - FK506 undoubtedly improved the survival advantage of hepatic allotransplantation.
      Hepatic-intestinal and multivisceral transplantation has also become a feasible
      therapy for patients with combined intestinal and liver failure. With better
      understanding of the immunologic and metabolic aspects of allo- and
      xenotransplantation, further clinical attempts to transplant animal organs to
      humans may be considered with the hope for a better outcome in the very near
      future.

PMID- 7522530
TI  - Role of thyrotropin in triiodothyronine generation in hypothyroidism.
AB  - Most of the circulating T3 is generated by monodeiodination of T4 in
      extrathyroidal tissue with only minor contribution by the thyroid gland. Since T3
      is the main active thyroid hormone and TSH is the major modulator of its
      synthesis and release by the thyroid gland, TSH may also play a significant role
      in synthesis and release of T3 by the peripheral tissues as documented in recent
      in vitro animal studies. However, the data regarding its influence on T4
      metabolism in humans is lacking. Hypothyroidism may provide an appropriate
      environment for assessing the influence of TSH in synthesis and release of T3 by
      the extrathyroidal tissues, since circulating T3 is almost totally derived via
      peripheral conversion of T4, and serum TSH varies from subnormal levels in
      central hypothyroidism to a wide range of supernormal concentration in the
      primary variety. This study determined the relationship between serum TSH
      concentration and T3 and T4 ratio, a reliable index of conversion of T4 into T3
      in peripheral tissues, in 75 subjects with hypothyroidism including both the
      primary and the central types. Serum T3 was significantly higher (p < 0.001) in
      primary hypothyroidism (1.48 +/- 0.13 mM/l) in comparison with the central type
      (0.71 +/- 0.09 mM/l) despite almost equally low serum T4 concentration in both
      groups. In primary hypothyroidism, T3:T4 ratio (0.026 +/- 0.0012) was
      significantly higher (p < 0.01) than normal (0.017 +/- 0.0010) along with
      supernormal TSH (71 +/- 6.4 mU/L) concentration prior to initiation of LT4
      replacement therapy and normalized (0.015 +/- 0.0008) on achieving euthyroid
      state with correction of serum TSH level (3.8 +/- 0.3 mU/L).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7522531
TI  - The medical treatment of non-toxic goiter: several questions remain.
AB  - In this review it is concluded that thyroxine (T4), triiodothyronine (T3) and
      iodine (KI), singly or in combination, are all effective in reducing the goiter
      size, but there is insufficient evidence to prove which is the best (possibly the
      combination of T4 + KI?). Higher doses are more effective than smaller, but also
      lead to more side-effects. Thus, the optimal dose has yet to be found. The
      suppression of the pituitary thyroid axis plays a major role in the treatment of
      non-toxic goiter, but it is not definite that this is the only mechanism
      responsible for the beneficial effect of the agents mentioned. In view of the
      lack of better evidence, it is simply suggested that non-toxic goiters in young
      persons should be initially treated aggressively with 200 micrograms of T4/day or
      more for some months. If the goiter shrinks then the dose should be gradually
      decreased. If the goiter persists, it is futile to continue with large doses for
      more than 6-12 months. One may continue with smaller doses, maintaining the serum
      TSH in the low-normal range. The treatment of benign thyroid nodules with
      thyroxine is controversial. Probably thyroxine is beneficial in about a third of
      the cases. For both non-toxic goiters and nodules, autonomy should be excluded
      before starting thyroxine treatment, and old age, cardiac disease and a poor
      general condition are contraindications.

PMID- 7522534
TI  - Iodine induced splitting of peptide bonds in human thyroglobulin.
AB  - Human thyroglobulin pretreated with iodine (1mM) at alkaline pH is split to small
      molecular weight fragments after reduction with dithiothreitol. Iodine
      pretreatment alone did not induce any changes in the thyroglobulin molecular
      weight.

PMID- 7522532
TI  - An update on management of differentiated thyroid carcinoma.
AB  - While some may still favor lobectomy, most experts recommend total thyroidectomy
      for DTC followed by radioablation of thyroid remnant with 131I. After such a
      treatment, serum Tg level serves as a useful marker of metastases of DTC.
      Radioiodine (131I) is a reasonable good treatment for small (mg in weight)
      deposits of metastases. However, large lesions, and those in the lungs and bones,
      do not respond well to clinically "safe" doses of 131I. Some experts suggest that
      employment of radiation dose based approach to 131I may improve the outcome of
      treatment of DTC. Agents that enhance the sensitivity of the tissues to radiation
      effects of 131I should be helpful and research needs to be encouraged in that
      area.

PMID- 7522533
TI  - L-thyroxine overdose: a case of marked, severe, prolonged, excess ingestion and
      review of the literature.
AB  - A case of a man with thyroid cancer who ingested between 0.9 and 3.3 mg l
      thyroxine per day for over 10 years (the highest dose for 3 years) is reported.
      This had been prescribed for suppression of TSH for a well differentiated thyroid
      cancer. He was essentially asymptomatic and suffered no apparent ill effects from
      this prolonged and markedly excessive dosage of l-thyroxine. The literature lists
      a wide range of ill effects from both chronic and acute thyroid hormone
      overdosage but also records many examples of tolerance to excessive levels of
      exogenous thyroid hormone. The various circumstances leading to thyroid hormone
      overdose and potential ill-effects are reviewed.

PMID- 7522535
TI  - Isochromosomes in neoplasia.
AB  - In order to ascertain the frequency and distribution of isochromosomes in
      neoplasia, we surveyed the cytogenetic data from 20,007 tumors with clonal
      chromosome aberrations reported in the literature. Tumor types for which at least
      50 cases with acquired aberrations and 10 cases with isochromosomes had been
      reported were selected, yielding a total of 18,160 neoplasms. Of these, 1,792
      cases (9.9%) displayed a total of 2,014 isochromosomes. The 9 most common
      isochromosomes (detected in at least 50 cases) were, in decreasing order of
      frequency, i(17q), i(8q), i(1q), i(12p), i(6p), i(7q), i(9q), i(5p), and i(21q).
      The frequency of isochromosomes varied among the different tumor types, with the
      highest incidence in germ cell neoplasms (60%) and the lowest in chronic
      myeloproliferative disorders (2.3%). Also, the spectrum of isochromosomes
      differed among the neoplasms. The most common isochromosomes in the different
      tumor types were i(11q), i(17q), and i(21q) in acute myeloid leukemia; i(9q),
      i(17q), and i(22q) in chronic myeloid leukemia; i(17q) in chronic
      myeloproliferative disorders; i(X)(q13), i(17q), and i(21q) in myelodysplastic
      syndromes; i(7q), i(9q), and i(17q) in acute lymphoblastic leukemia; i(1q),
      i(7q), i(8q), and i(17q) in chronic lymphoproliferative disorders; i(1q), i(6p),
      i(9p), i(17q), and i(21q) in Hodgkin's disease; i(1q), i(6p), and i(17q) in non
      Hodgkin's lymphoma; i(1q), i(8q), and i(17q) in adenocarcinoma; i(1q), i(3q),
      i(5p), and i(8q) in squamous cell carcinoma; i(5p), i(8q), and i(11q) in
      transitional cell carcinoma; i(1q), i(7q), and i(17q) in Wilms' tumor; i(1q),
      i(12p), and i(17q) in germ cell neoplasms; i(1p), i(1q), i(6p), and i(17q) in
      sarcoma; i(5p), i(6p), i(7p), and i(21q) in mesothelioma; i(1q), i(6p), and
      i(17q) in malignant neurogenic neoplasms; i(1q), i(6p), and i(17q) in
      retinoblastoma; and i(1q), i(6p), and i(8q) in malignant melanoma.

PMID- 7522536
TI  - Optimizing comparative genomic hybridization for analysis of DNA sequence copy
      number changes in solid tumors.
AB  - Comparative genomic hybridization (CGH) is a powerful new method for molecular
      cytogenetic analysis of cancer. In a single hybridization, CGH provides an
      overview of DNA sequence copy number changes (losses, deletions, gains,
      amplifications) in a tumor specimen and maps these changes on normal chromosomes.
      CGH is based on the in situ hybridization of differentially labeled total genomic
      tumor DNA and normal reference DNA to normal human metaphase chromosomes. After
      hybridization and fluorescent staining of the bound DNAs, copy number variations
      among the different sequences in the tumor DNA are detected by measuring the
      tumor/normal fluorescence intensity ratio for each locus in the target metaphase
      chromosomes. CGH is in particular useful for analysis of DNA sequence copy number
      changes in common solid tumors where high-quality metaphase preparations are
      often difficult to make, and where complex karyotypes with numerous markers,
      double minutes, and homogeneously stained chromosomal regions are common. CGH
      only detects changes that are present in a substantial proportion of tumor cells
      (i.e., clonal aberrations). It does not reveal translocations, inversions, and
      other aberrations that do not change copy number. At present, CGH is a research
      tool that complements previous methods for genetic analysis. CGH will advance our
      understanding of the genetic progression of cancer and highlight important
      genomic regions for further study. Direct clinical applications of CGH are
      possible, but will require further development and validation of the technique.
      We describe here our recent optimized procedures for CGH, including DNA labeling,
      hybridization, fluorescence microscopy, digital image analysis, data
      interpretation, and quality control, emphasizing those steps that are most
      critical. We will also assess sensitivity and resolution limits of CGH as well as
      discuss possible future technical improvements.

PMID- 7522537
TI  - Fluorescence in situ hybridisation studies to characterise complete and partial
      monosomy 7 in myeloid disorders.
AB  - Eight patients with myeloid disorders characterised by a karyotype including
      apparent monosomy or partial monosomy 7, in the presence of a ring or marker
      chromosome, were investigated by fluorescence in situ hybridisation (FISH) with a
      chromosome 7 centromere-specific probe and an Alu-PCR derived chromosome 7 paint.
      In 4 of 5 cases a ring chromosome was shown to be of chromosome 7 origin; in one
      of these the apparent ring was shown to consist solely of chromosome 7
      centromeric material, and in the fifth case the ring was derived from chromosome
      18. In three cases monosomy 7 had arisen during the course of karyotype evolution
      and was clearly not the primary cytogenetic abnormality. One further case
      demonstrated fragmentation and cryptic translocation of chromosome 7 material. In
      the last case a chromosome described as der(l)t(1;7)(p11;p11) was redefined as
      dic(1;7)(p11;q11). The application of FISH has enabled a more accurate
      characterisation of chromosome abnormalities, and extended studies of this type
      may eventually lead to more precise prognostic groups defined by karyotype.

PMID- 7522538
TI  - TP53 mutations are frequent in malignant NF1 tumors.
AB  - Neurofibromatosis type I (NFI) is a common autosomal dominant disorder with an
      increased risk for developing benign and malignant tumors. The NFI gene has been
      cloned and maps to 17q11.2, and the gene product acts as a tumor suppressor gene.
      Here we analyzed the role of mutations in TP53 in four malignant NFI tumors.
      Mutations were found in 3 out of 4 tumors. One of these mutations is a common
      missense mutation in codon 278 in one of the previously identified hot spots for
      mutations. The two other are hitherto unreported mutations, including a splice
      mutation of exon 3 and a nonsense mutation in exon 4. In addition, these four
      tumors also showed loss of heterozygosity (LOH) for markers on chromosome 17 in
      the region of TP53. Malignant NFI tumors are initiated by a somatic inactivation
      of the second NFI allele. Tumor progression, however, occurs by accumulation of
      additional genetic abnormalities, such as homozygous inactivation of TP53, as
      demonstrated in this paper.

PMID- 7522539
TI  - Submicroscopic deletions of 3p sequences in pleomorphic adenomas with
      t(3;8)(p21;q12).
AB  - A subgroup of benign pleomorphic adenomas of the salivary glands is characterized
      by translocations, or on rare occasions deletions, with breakpoints at 3p21. We
      have applied restriction fragment length polymorphism (RFLP) analysis to assess
      the frequency of allelic losses at four different loci located within 3p21-->p25
      in 35 pleomorphic adenomas, 18 of which were also karyotyped. Parallel analysis
      of constitutional and tumor DNAs in informative tumors revealed that all patients
      retained heterozygosity in their tumor DNA at the D3S2 and RAF1 loci. Among the
      29 tumors informative for THRB three showed loss of heterozygosity (LOH). All
      three tumors had a t(3;8)(p21;q12). Of the 23 tumors informative for D3F15S2, one
      showed LOH. This tumor also had a t(3;8)(p21;q12). To further map the deletions
      in relation to the 3p21 translocation breakpoint, we also sublocalized the THRB
      locus. Using in situ hybridization we assigned the gene to 3p24.1-3. The fact
      that none of the tumors with loss of 3p alleles showed cytogenetic evidence of
      deletions indicates that the losses are submicroscopic, probably interstitial,
      and in most cases distal to the 3p21 breakpoint. This was confirmed in one case
      with loss of a THRB allele where both proximal (D3F15S2) and distal (RAF1)
      markers retained heterozygosity. Our results suggest that deletion of 3p
      sequences might be of progressional importance in a subset of pleomorphic
      adenomas with t(3;8)(p21;q12).

PMID- 7522541
TI  - Putative "MDR enhancer" is located on human chromosome 20 and not linked to the
      MDR1 gene on chromosome 7.
AB  - The physiologic expression of the human multidrug resistance MDR1 gene product P
      glycoprotein is controlled in a tissue- and cell-specific manner, but the
      regulatory mechanisms have not been characterized in great detail. Studies by
      Kohno et al. [(1990) J Biol Chem 265:19690-19696] suggested that a tissue
      specific enhancer element located approximately 10 kb upstream from the major
      MDR1 transcription start site may act to increase the levels of transcription in
      cultured adrenal and kidney cells. Using this putative "MDR enhancer" as a probe,
      we isolated a 14 kb DNA fragment from a genomic DNA library prepared from human
      fetal liver. The restriction map and partial nucleotide sequence of this DNA
      fragment were consistent with the previously described data obtained for a
      similar piece of genomic DNA derived from human placenta by Kohno et al. (ibid.).
      Pulsed-field gel electrophoresis of large genomic DNA fragments, however, showed
      that the DNA sequences, including the putative "MDR enhancer," were not linked to
      the MDR1 gene. Fluorescence in situ hybridization analysis revealed that this
      enhancer-like element is located on chromosome 20 at band q13.1 and is,
      therefore, distinct from the MDR locus on chromosome 7, band q21.1. Thus, this
      putative regulatory element does not modulate the tissue specificity of
      expression of the MDR1 gene in vivo, but may play a role in the regulation of
      expression of another, so far unknown gene.

PMID- 7522542
TI  - Two distinct deleted regions on the short arm of chromosome 1 in neuroblastoma.
AB  - The short arm of chromosome 1p is the most frequently altered chromosome segment
      in neuroblastoma. The alterations, mainly deletions, are thought to be indicative
      of the presence of a tumor suppressor gene. To further refine the chromosome
      localization of this gene, we have studied paired constitutional and tumor DNA
      from a series of 60 patients with neuroblastoma at 2 minisatellite and 23
      microsatellite loci dispersed along the short arm of chromosome 1. Twenty-two
      cases (37%) demonstrated loss of heterozygosity (LOH) at one or more loci on 1p.
      Surprisingly, the pattern of LOH enabled the identification of two distinct
      consensus regions of deletions. In agreement with previous reports, one region
      mapped to the distal short arm of chromosome 1. The other region was localized
      more proximally on 1p. Deletions observed in tumors involve either one or both of
      these regions. We show that the correlation between NMYC amplification and 1p
      deletion is limited to the deletions which involve the proximal region either
      alone or together with the distal region. These results suggest that two tumor
      suppressor genes on 1p might be involved in the development of neuroblastoma.
      Finally, we show that somatic mutations at microsatellite loci, frequently
      observed in other types of cancer, are rare events in neuroblastoma.

PMID- 7522540
TI  - Simple numeric abnormalities as primary karyotype changes in ovarian carcinoma.
AB  - Simple near-diploid karyotypes in ovarian cancer may indicate either primary
      alterations related to tumor pathogenesis or abnormalities associated with early
      tumor progression. We have identified a series of 13 epithelial ovarian tumors
      with very simple karyotypes. Specifically, these karyotypes were near-diploid and
      displayed numeric abnormalities alone or combined with one or two structural
      alterations. The present series includes samples from 10 patients with newly
      diagnosed adenocarcinomas and 3 patients having borderline malignancies.
      Recurrent numeric abnormalities were identified and included 9/13 cases (69%)
      with +12, eight cases (62%) with +8, five cases (38%) with +7, three cases (23%)
      each with +3 or +5, and two cases (15%) with -X. Five cases in this series
      displayed certain numeric abnormalities (+12, +7, and -X) as the sole anomalies,
      thereby qualifying as primary karyotype changes. Of the 6 cases with structural
      abnormalities, 4 involved chromosome 19, 2 involved chromosome 1, and the
      remaining abnormalities or translocation partners involved other chromosomes.
      These findings indicate that some numeric abnormalities are primary karyotype
      alterations in patients with malignant epithelial ovarian tumors and that
      chromosome 19 may be preferrentially involved in structural rearrangements during
      early tumor progression.

PMID- 7522543
TI  - Cytogenetic analysis of a choroid plexus papilloma.
AB  - We report the cytogenetic analysis of a choroid plexus papilloma, a benign tumor,
      with a modal number of 56 chromosomes. In our review of the few reported
      karyotypes of choroid plexus tumors, we found no predictive relationship between
      the karyotype and the pathologic diagnosis or outcome.

PMID- 7522544
TI  - Common region of deletion on the long arm of chromosome 6 in non-Hodgkin's
      lymphoma and acute lymphoblastic leukaemia.
AB  - We have used fluorescence in situ hybridisation (FISH) with a series of yeast
      artificial chromosome (YAC) clones that map to the long arm of chromosome 6 (6q)
      to define the region(s) of deletion in seven cases of non-Hodgkin's lymphoma
      (NHL), in which a deletion of 6q had been detected by conventional cytogenetics.
      The FISH analysis detected two regions of deletion: (i) A proximal region flanked
      by M6P1 (6q14-15) and FYN (6q21), containing D6S246, which was missing in all
      seven cases. This locus was also found to be deleted in all six cases of acute
      lymphoblastic leukaemia (ALL) studied previously. (ii) A second region of 6q,
      which was distal to 6q23.1 (D6S238) and included ESR (6q25.1) and D6S281 (6q27),
      which was shown to be present in all our cases of ALL, was found to be deleted in
      4 of the 7 cases of NHL. Our results support the suggestion that tumour
      suppressor genes, involved in the pathogenesis of lymphoid malignancies, may be
      present within these regions.

PMID- 7522547
TI  - Tamoxifen and estrogen lower circulating lipoprotein(a) concentrations in healthy
      postmenopausal women.
AB  - Data in the literature suggest that circulating levels of lipoprotein(a) [Lp(a)]
      and insulinlike growth factor I (IGF-I) respond similarly to therapy with growth
      hormone, estrogen, or tamoxifen. To more clearly document these relations, we
      designed a randomized, double-blind, placebo-controlled study of the effects of
      tamoxifen and continuous estrogen on circulating levels of Lp(a), IGF-I, and IGF
      binding protein 3 (IGFBP-3) in healthy postmenopausal women. Both estrogen and
      tamoxifen decreased serum levels of IGF-I to 30% below baseline during the 3
      months of treatment, while IGFBP-3 levels were unchanged. Plasma Lp(a) levels
      decreased to 24% below baseline after 1 month of treatment with either estrogen
      or tamoxifen (P < .05 for estrogen only); after 3 months Lp(a) decreased to 34%
      below baseline with tamoxifen therapy (P < .05) but returned to only 16% below
      baseline with estrogen. The correlation between Lp(a) and IGF-I was highly
      significant (P < .0001). We conclude that (1) tamoxifen lowers plasma Lp(a)
      levels in healthy postmenopausal women, (2) the suppressive effects of tamoxifen
      and estrogen on circulating Lp(a) concentration diverge after the first month of
      therapy, and (3) circulating levels of Lp(a) and IGF-I are strongly correlated
      with each other, an indication that they may share regulatory influences.

PMID- 7522549
TI  - The dehydrating function of the descending colon in relationship to crypt
      function.
AB  - Very high pressure is required to generate hard faeces approximately 5-10
      atmospheres. This is much more than can be supplied by the mechanical force from
      the muscular wall of the colon. Osmotic pressure (at least 200 mOsm) can generate
      the necessary suction forces required to consolidate faeces. The colon has a
      hypertonic absorbate (net above plasma approximately 500 mOsm) in vivo.
      Fluorescence imaging of perifused rat descending colonic mucosa shows high steady
      state Na+ concentrations (600 mM) in the intercryptal extracellular space and low
      [Na+] present in the crypt lumen. This [Na+] distribution generates an osmotic
      pressure gradient across the crypt luminal wall resulting in a fluid inflow into
      the crypt lumen. Direct observation using confocal fluorescence microscopy of
      FITC dextran (mol. wt. 10,000) shows that there is concentration polarisation of
      the dextran in the upper 30% of the crypt lumen. The time course and steady state
      distribution of concentration polarisation of fluorescent dyes within the crypt
      lumen permit an estimation of the fluid convection rate along the length of the
      crypt lumen. This is sufficient to account for the majority of fluid absorption
      by the colon. Observation of the suction force on agarose gels by rat descending
      colon in vivo shows that the colon generates up to 4,000 cm H2O suction pressure
      on the stiff gels, this is accompanied by a hypertonic absorbate from the gels of
      800 mOsm. Disruption of the colonic mucosa by bile salts reduces the suction
      pressure to about 40 cm H2O.

PMID- 7522548
TI  - Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B
      mobilization and induction of vascular cell adhesion molecule-1 in endothelial
      cells stimulated to generate radicals.
AB  - Cell adhesion to endothelial cells stimulated by tumor necrosis factor-alpha
      (TNF) is due to induction of surface receptors, such as vascular cell adhesion
      molecule-1 (VCAM-1). The antioxidant pyrrolidine dithiocarbamate (PDTC)
      specifically inhibits activation of nuclear factor-kappa B (NF-kappa B). Since
      kappa B motifs are present in VCAM-1 and intercellular adhesion molecule-1 (ICAM
      1) promoters, we used PDTC to study the regulatory mechanisms of VCAM-1 and ICAM
      1 induction and subsequent monocyte adhesion in TNF-treated human umbilical vein
      endothelial cells (HUVECs). PDTC or N-acetylcysteine dose dependently reduced TNF
      induced VCAM-1 but not ICAM-1 surface protein (also in human umbilical arterial
      endothelial cells) and mRNA expression (by 70% at 100 mumol/L PDTC) in HUVECs as
      assessed by flow cytometry and polymerase chain reaction. Gel-shift analysis in
      HUVECs demonstrated that PDTC prevented NF-kappa B mobilization by TNF,
      suggesting that only VCAM-1 induction was controlled by NF-kappa B. Since HUVECs
      released superoxide anions in response to TNF, and H2O2 induces VCAM-1, PDTC may
      act as a radical scavenger. Although ICAM-1 induction was unaffected, inhibitors
      of NADPH oxidase (apocynin) or cytochrome P-450 (SKF525a) suppressed VCAM-1
      induction by TNF, revealing that several radical-generating systems are involved
      in its regulation. PDTC, apocynin, or SKF525a decreased adhesion of monocytic
      U937 cells to TNF-treated HUVECs (by 75% at 100 mumol/L PDTC). Inhibition by anti
      VCAM-1 monoclonal antibody 1G11 indicated that U937 adhesion was VCAM-1 dependent
      and suppression by antioxidants was due to reduced VCAM-1 induction.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7522545
TI  - Orbital exenteration in 95 cases of primary conjunctival malignant melanoma.
AB  - The role of orbital exenteration in the management of malignant melanoma of the
      conjunctiva has been underexplored. The outcome in 95 patients with this
      condition, who underwent exenteration as a primary treatment (n = 36) or after
      failure of other treatment (n = 59) for early to advanced stages of the disease,
      was evaluated. The majority of treated cases had multicentric melanomas sited at
      prognostically unfavourable locations. In the group of tumours with a maximum
      thickness of 1.0 mm no melanoma related mortality was noted. Melanomas thicker
      than 1.0 mm were associated with a mortality varying between 33% and 50%,
      independent of whether exenteration was performed as primary or secondary
      treatment. An especially poor outcome was noted for the group of caruncular
      melanomas despite exenteration. These findings indicate that total eradication of
      tumour should be performed at an early stage. For this purpose, a combination of
      debulking surgery and adjunctive cryotherapy or beta radiotherapy is more
      appropriate than orbital exenteration which causes disfigurement and blindness.
      Exenteration of the orbit should be reserved as a palliative procedure for
      advanced stages of neoplastic disease.

PMID- 7522546
TI  - Production of IGF-I and IGF binding proteins by retinal cells in vitro.
AB  - Insulin-like growth factor I (IGF-I) and its associated binding proteins (IGFBPs)
      have been identified in retinal tissues but their precise cellular origin remains
      unclear. The aim of this study was to examine the ability of three retinal cell
      types (microvascular endothelial cells, pericytes, and pigment epithelial cells)
      and a non-retinal cell type (Tenon's fibroblasts) to produce IGF-I and cell
      specific IGFBPs in vitro. Using a radioimmunoassay we demonstrated that all four
      cell types produce IGF-I and that this production continued over a 72 hour
      period. In addition, western ligand blotting revealed that each cell type
      produced at least one IGFBP and that each cell type produced a different IGFBP
      profile. Endothelial cells produced a 24 kDa band only, pericytes produced both a
      24 kDa and a 34 kDa band, retinal pigment epithelial cells produced a 38-41 kDa
      band, while fibroblasts produced both a 24 kDa and a 30 kDa band. Laser scanning
      densitometry demonstrated that in the majority of experiments the IGFBPs
      accumulated in the culture medium over a 72 hour period. Neither IGF-I nor IGFBPs
      were observed in cell lysates indicating de novo synthesis and secretion in
      vitro. These results suggest an autocrine/paracrine function for IGF-I and its
      associated binding proteins which may play a significant role in both retinal
      physiology and disease.

PMID- 7522550
TI  - DNA triplexes: solution structures, hydration sites, energetics, interactions,
      and function.

PMID- 7522551
TI  - Molecular dynamics simulation of MHC-peptide complexes as a tool for predicting
      potential T cell epitopes.
AB  - The class I major histocompatibility complex-encoded HLA-B*2705 protein was
      simulated in complex with six different peptides exhibiting unexpected structure
      activity relationships. Various structural and dynamical properties of the
      solvated protein-peptide complexes (atomic fluctuations, solvent-accessible
      surface areas, hydrogen bonding pattern) were found to be in qualitative
      agreement with the available binding data. Peptides that have been experimentally
      shown to bind to the protein remained tightly anchored to the MHC molecule,
      whereas nonbinders were significantly more weakly complexes to the protein and
      progressively dissociate from it at their N- and C-terminal ends. The molecular
      dynamics simulations emphasize the unexpectedly important role of secondary
      anchors (positions 1 and 3) in influencing the MHC-bound conformation of
      antigenic nonapeptides. Furthermore, it confirms that dominant anchor residues
      cannot solely account for peptide binding to a class I MHC molecule. The
      molecular dynamics method could be used as a complementary tool to T cell epitope
      predictions from the primary sequences of proteins of immunological interest. It
      is better suited to MHC proteins for which a crystal structure already exists.
      Furthermore, it may facilitate the engineering of T cell epitopes as well as the
      rational design of new MHC inhibitors designed to fit optimally the peptide
      binding cleft.

PMID- 7522552
TI  - Functional analysis and modeling of a conformationally constrained Arg-Gly-Asp
      sequence inserted into human lysozyme.
AB  - To examine the effect of a conformational constraint introduced into the Arg-Gly
      Asp (RGD) sequence on cell adhesion activity, we have constructed mutant proteins
      by inserting RGD-containing sequences flanked by two Cys residues between Val74
      and Asn75 of human lysozyme. CRGDC-, CRGDSC-, and CGRGDSC-inserted mutant
      lysozymes were expressed in yeast, purified, and designated as Cys-RGD3, Cys
      RGD4, and Cys-RGD5, respectively. In baby hamster kidney cells, these mutants
      were shown to possess high cell adhesion activity by interaction with vitronectin
      receptor (integrin alpha v beta 3), and this activity is 2-3-fold higher than
      that of the RGDS-inserted mutant lysozyme, RGD4. The mutant proteins also
      inhibited the binding of human fibrinogen to its receptor (integrin alpha IIb
      beta 3) at a lower concentration than the RGD4 protein. Peptide mapping and mass
      spectrometric analyses showed that the two inserted Cys residues in these mutants
      are linked to each other without any effects on the mode of the four disulfide
      bonds present in native human lysozyme. These results suggest that the
      introduction of a conformational constraint into the RGD region significantly
      increases the cell adhesion activity. The conformation of the RGD region in Cys
      RGD4 was modeled by a Monte Carlo simulation. Most of the sampled conformations
      were grouped into three classes; the first is characterized by an extended Gly
      conformation, the second assumes a type II' beta turn, and the third has a salt
      bridge between Arg and Asp.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522553
TI  - Energy transfer studies of the distances between the colchicine, ruthenium red,
      and bisANS binding sites on calf brain tubulin.
AB  - Fluorescence energy transfer experiments were performed in order to measure the
      spatial separation between the colchine and Ruthenium Red binding sites, the high
      affinity bisANS and Ruthenium Red sites, and the allocolchicine and high-affinity
      bisANS sites on calf brain tubulin. Energy transfer was observed between both
      colchicine and allocolchicine and Ruthenium Red, resulting in a distance of 40-45
      A between these sites on the tubulin molecule. No detectable energy transfer
      could be observed when allocolchicine was used as fluorescence donor and bisANS
      as acceptor or when bisANS was used as donor and Ruthenium Red as acceptor. This
      indicates that the distance of separation between the allocolchicine and bisANS
      sites is greater than 50 A, while that between the bisANS and Ruthenium Red sites
      is greater than 72 A. On the basis of these and previous distance measurements
      (Ward & Timasheff, 1988), two triangles of binding sites have been defined
      (colchicine-bisANS-E-site and colchicine-bisANS-Ruthenium Red). Since the
      dihedral angle between them is not known, a schematic model has been drawn with
      all the sites located in a single plane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522554
TI  - Continuous in vitro evolution of bacteriophage RNA polymerase promoters.
AB  - Rapid in vitro evolution of bacteriophage T7, T3, and SP6 RNA polymerase
      promoters was achieved by a method that allows continuous enrichment of DNAs that
      contain functional promoter elements. This method exploits the ability of a
      special class of nucleic acid molecules to replicate continuously in the presence
      of both a reverse transcriptase and a DNA-dependent RNA polymerase. Replication
      involves the synthesis of both RNA and cDNA intermediates. The cDNA strand
      contains an embedded promoter sequence, which becomes converted to a functional
      double-stranded promoter element, leading to the production of RNA transcripts.
      Synthetic cDNAs, including those that contain randomized promoter sequences, can
      be used to initiate the amplification cycle. However, only those cDNAs that
      contain functional promoter sequences are able to produce RNA transcripts.
      Furthermore, each RNA transcript encodes the RNA polymerase promoter sequence
      that was responsible for initiation of its own transcription. Thus, the
      population of amplifying molecules quickly becomes enriched for those templates
      that encode functional promoters. Optimal promoter sequences for phage T7, T3,
      and SP6 RNA polymerase were identified after a 2-h amplification reaction,
      initiated in each case with a pool of synthetic cDNAs encoding greater than
      10(10) promoter sequence variants.

PMID- 7522555
TI  - Reaction of phthalate dioxygenase reductase with NADH and NAD: kinetic and
      spectral characterization of intermediates.
AB  - Phthalate dioxygenase reductase (PDR) is an electron transferase that contains
      FMN, which accepts a hydride from NADH, and a [2Fe-2S] center, which transfers
      electrons to phthalate dioxygenase. The reduction of PDR by NADH has been studied
      by stopped-flow spectroscopy. Data from studies using both portio- and deuterio
      NADH were analyzed by nonlinear curve fitting and numerical simulation
      techniques. The results of these analyses indicate that the reductive half
      reaction of PDR consists of five distinct kinetic phases: (a) NADH binds to form
      a primary Michaelis complex (MC-1) (Kd = 50 microM). (b) The enzyme undergoes a
      structural change (116 +/- 5 s-1) resulting in a charge-transfer complex (CT-1).
      (c) The next phase in the reaction shows a deuterium isotope effect of 7.0 when
      (4R)-[2H]NADH (NADD) is substituted for NADH, identifying this step as the one
      involving hydride transfer. The rate of hydride transfer from NADH to FMN is 70 s
      1, and this process results in a charge-transfer intermediate between the flavin
      hydroquinone anion and NAD (CT). (d) Internal electron transfer from the flavin
      to the iron-sulfur center, which is only 35 +/- 4 s-1, then results in an
      intermediate consisting of a reduced [2Fe-2S] center and a neutral flavin
      semiquinone (SQ). It is surprising that this rate is so slow, since the shortest
      interatomic distance between these centers is only 4.7 A [Correll, C. C., et al.
      (1992) Science 258, 1604-1610]. The 2-electron-reduced form of PDR (SQ in Figure
      1) binds weakly to the reaction product, NAD (Kd = 3.7 mM), but forms a tight
      complex with NADH (Kd = 10 microM). (e) Two molecules of the reduced iron-sulfur
      flavin semiquinone (SQ) form of PDR then undergo a relatively slow second-order
      disproportionation reaction, resulting in one molecule of 3-electron-reduced PDR
      and one molecule of 1-electron-reduced PDR. The latter reacts rapidly with excess
      NADH to form a 3-electron-reduced PDR.

PMID- 7522557
TI  - Characterization of cation-binding sequences in the platelet integrin GPIIb-IIIa
      (alpha IIb beta 3) by terbium luminescence.
AB  - The binding of cations to purified GPIIb-IIIa (alpha IIb beta 3) and synthetic
      peptides corresponding to the potential cation-binding sites within this integrin
      has been assessed by terbium luminescence spectroscopy. Tb3+ supported fibrinogen
      binding to purified GPIIb-IIIa, at lower concentrations than Ca2+, consistent
      with its higher affinity for cation-binding motifs. Titration analyses indicated
      the presence of five Tb(3+)-binding sites of relatively high affinity in the
      receptor. These sites also could be filled by divalent cations. Six sequences
      within GPIIb-IIIa have the appropriate spacing of five of the usual six
      coordination sites for cations in functional Ca(2+)-binding EF-hand motifs.
      Peptides containing Tyr and/or Trp at selected positions as fluorescence energy
      donors were synthesized, and their Tb(3+)-binding capacity was assessed. The four
      potential Ca(2+)-binding sequences in the GPIIb subunit, GPIIb 242-255, 296-309,
      364-377, and 425-438, were functional, despite lacking the usual Glu residue at
      the terminal coordination position. These peptides bound Tb3+ with the same
      affinity as typical Ca(2+)-binding loop peptides and also bound Ca2+ and other
      divalent cations without preference. Of the two candidate GPIIIa sequences, 118
      131 and 208-221, the former bound Tb3+ and divalent cations with an affinity
      similar to that of the GPIIb peptides, whereas the latter peptide was not
      functional. This functional difference, as well as data obtained with substituted
      peptides, emphasizes the importance of the first coordination position for
      interaction of synthetic peptide loops with cations. Together, these data
      identify the five cation-binding sites within intact GPIIb-IIIa.

PMID- 7522556
TI  - Interaction of the reverse transcriptase of human immunodeficiency virus type 1
      with DNA.
AB  - During DNA synthesis, the binding of human immunodeficiency virus (HIV) reverse
      transcriptase (RT) to the template-primer precedes its binding to nucleotide
      triphosphates. The interaction of oligonucleotide DNA with HIV-1 RT was
      investigated by using a gel retardation assay. Both homodimeric (p66/p66) and
      heterodimeric (p66/p51) isoforms of HIV-1 RT were capable of binding the DNA
      oligomers. Thus, all further studies on the interaction of HIV-1 RT with DNA were
      done with heterodimeric RT. We have studied the conditions for optimal binding.
      The formation of the RT-DNA complex was primer-independent, and the extent of DNA
      binding was indistinguishable for both single-stranded and double-stranded DNA
      (either blunt-ended or recessed). The DNA binding activity of the RT was found to
      be dependent on oligonucleotide length. HIV-1 RT binds DNA with no apparent
      sequence specificity. Hence, this enzyme belongs to the sequence nonspecific DNA
      binding proteins. The interaction was found to be independent of DNA synthesis.
      The formation of the RT-DNA complex was not influenced by the presence of either
      template-complementary or noncomplementary dNTPs, indicating that neither DNA
      polymerization nor binding of the RT to the dNTP affects the stability of the
      complex. The gel retardation assay was utilized to examine also the effect of
      various HIV-1 RT inhibitors (i.e., AZT-TP, ddTTP, TIBO, and 3,5,8-trihydroxy-4
      quinolone) on the enzyme-DNA interaction. The results indicate differences in the
      modes of action of these compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522558
TI  - Osmolyte mediation of T7 DNA polymerase and plasmid DNA stability.
AB  - The thermal stability of T7 DNA polymerase and pGEM4Z plasmid DNA in the presence
      and absence of the osmolyte N-methylglycine (sarcosine) was determined by means
      of UV spectroscopy. The decrease in melting temperature observed upon addition of
      sarcosine to solutions containing the plasmid DNA is linear with the
      concentration of sarcosine present. The enthalpy of the transition is also linear
      in its relationship to the melting temperature, and the entropy of the transition
      is linear in the natural log of the melting temperature. The slopes of both the
      entropic and enthalpic plots are equal. Destabilization of the plasmid DNA is
      observed to be entropically driven. The melting temperature of the T7 DNA
      polymerase complex is increased from 41 degrees C by addition of sarcosine to the
      solution. The relationship between the amount of sarcosine added and the melting
      temperature is linear, with a temperature of 61 degrees C observed for a 6 M
      solution. No clear trend of the effect of sarcosine on the enthalpy or entropy of
      the transitions could be observed.

PMID- 7522560
TI  - Nuclear translocation of angiogenic proteins in endothelial cells: an essential
      step in angiogenesis.

PMID- 7522559
TI  - Polyglutamylation of tubulin as a progressive regulator of in vitro interactions
      between the microtubule-associated protein Tau and tubulin.
AB  - The multiple functions of microtubules are mediated by various structural and
      motor microtubule-associated proteins (MAPs). To harmonize these functions in
      different places of a single cell, the key problem is to regulate the
      interactions of these proteins with microtubules. The chemical diversity of
      tubulin isoforms, which constitute the microtubule wall, could represent a
      molecular basis for this control. Using an in vitro assay of ligand blotting, we
      found that the microtubule-associated protein Tau interacts differentially with
      the diverse posttranslationally-modified isotubulins: its binding is mainly
      restricted to moderately-modified alpha- and beta-tubulin isoforms. We obtained
      evidence that the recently-discovered polyglutamylation, which consists of the
      sequential, posttranslational addition of one to six glutamyl units to both alpha
      and beta-tubulin subunits, regulates the binding of Tau as a function of its
      chain length. The relative affinity of Tau, very low for unmodified tubulin,
      increases progressively for isotubulins carrying from one to three glutamyl
      units, reaches an optimal value, and then decreases progressively when the
      polygutamyl chain lengthens up to six residues. Our results suggest that the
      unmodified C-terminus of tubulin exerts a constitutive inhibition on Tau binding,
      probably by locking the MAP-binding site, and that this inhibition could be first
      released and then restored as the polyglutamyl chain grows. As the
      posttranslational chain does not appear to interact directly with Tau, it is
      thought that the growth of this chain from one to six glutamyl units causes a
      progressive, conformational shift in the structure of the C-terminal domain of
      tubulin, thus leading to the observed modulation of affinity.

PMID- 7522561
TI  - Escherichia coli proline tRNA synthetase is sensitive to changes in the core
      region of tRNA(Pro).
AB  - To investigate the relationship between tRNA conformation and specific
      recognition by aminoacyl-tRNA synthetases, a full-length tRNA molecule was
      assembled by annealing together two oligonucleotides representing fragments of
      Escherichia coli tRNA(Pro). A shorter chemically synthesized 5'-fragment (7-18
      nucleotides) was combined with an in vitro transcribed 3'-fragment (59
      nucleotides). Despite a break in the phosphodiester backbone between nucleotides
      U17a and G18, this tRNA molecule was an efficient substrate for class II
      Escherichia coli proline tRNA synthetase. While the deletion of three D-loop
      nucleotides (U17a, U17, and C16) was tolerated, removal of G15 and A14
      significantly reduced aminoacylation efficiency. Hybrid DNA-RNA "annealed"
      substrates were also prepared and assayed for aminoacylation. Native gel
      electrophoresis was used to compare the global folding of the various substrates
      tested. The results of these studies suggest that proline tRNA synthetase is
      sensitive to changes in the core region of tRNA(Pro) through which information
      required for efficient aminoacylation may be transmitted. In particular,
      nucleotides in the D-loop and backbone functional groups in the D-stem appear to
      be critical for maintaining a tRNA structure that is optimal for recognition by
      proline tRNA synthetase in vitro.

PMID- 7522562
TI  - Sequence dependence of stability for coaxial stacking of RNA helixes with Watson
      Crick base paired interfaces.
AB  - Thermodynamic parameters from UV melting studies are reported for the helix-helix
      interfaces of coaxially stacked helixes in RNA. The model system consists of a
      short oligomer binding to a four-nucleotide overhang at the end of a hairpin
      stem, creating the helix-helix interface. Interfaces containing Watson-Crick base
      pairs are approximately 1 kcal/mol more stable than the corresponding nearest
      neighbor interaction in an uninterrupted helix. Thus the sequence dependence of
      stability for coaxially stacked interfaces is similar to that for regular
      helixes. This provides experimental evidence for an assumption that has been
      shown to improve predictions of RNA secondary structure [Walter, A. E., Turner,
      D. H., Kim, J., Lyttle, M. H., Muller, P., Mathews, D. H., & Zuker, M. (1994)
      Proc. Natl. Acad. Sci. U.S.A. (in press)]. The results should also be useful for
      modeling three-dimensional structures of RNA.

PMID- 7522563
TI  - Single-channel activity induced in mitoplasts by alkaline pH.
AB  - Exposure of patch-clamped mitoplasts to alkaline pH induces a reversible
      conductance increase (Antonenko, Yu. N., Kinnally, K.W. and Tedeschi, H. (1991)
      J. Membr. Biol. 124, 151-158) which is due to an increase in open probability of
      a channel activity of 15 pS and larger transitions. The present study defines in
      more detail some of the characteristics of the channel activity involved in this
      conductance increase. The results suggest the presence of two channels one
      slightly cation-selective of approx. 15 pS (referred to here as alkaline-induced
      cation-selective activity, ACA) and another slightly anion selective of approx.
      45 pS (referred to as alkaline-induced anion-selective activity, AAA). The
      possible implication of these results in relation to other channels and the
      permeability transitions reported by others using mitochondrial suspensions is
      discussed.

PMID- 7522564
TI  - Simultaneous influence of erythrocyte deformability and macromolecules in the
      medium on erythrocyte aggregation: a kinetic study by a laser scattering
      technique.
AB  - The aggregation and sedimentation kinetics of human erythrocytes was studied by
      modifying the cellular properties and medium compositions simultaneously.
      Dextrans of average molecular weight 70400 and 494000 were used to provide
      suspending medium modifications, while diamide (diazene dicarboxylic acid bis(N,N
      dimethylamide)) was used to alter the membrane structural properties. Laser
      scattering method was employed for this study, and it was compared with a kinetic
      method combined with a low-shear rheoscope and an image analyzer. From scattered
      light intensity profiles continuously obtained during aggregation of erythrocytes
      and sedimentation of the aggregates, characteristic kinetic parameters were
      computed. Kinetic parameters obtained from a phase of the one-dimensional
      aggregate formation and sedimentation corresponded well to the velocity of
      rouleaux formation obtained by the low-shear rheoscope technique. Dextrans
      accelerated the erythrocyte aggregation and the sedimentation, and diamide
      treatment suppressed the process by decreasing the erythrocyte deformability. The
      aggregating force by dextrans overcame the disaggregating force by the decreased
      deformability. However, the arrangement of erythrocytes as expressed in specific
      units for aggregates (i.e., rouleaux) became irregular by decreasing the
      erythrocyte deformability. In conclusion, the progression of erythrocyte
      aggregation and the structure of the aggregates were dependent on both
      erythrocyte properties and macromolecules in the medium.

PMID- 7522565
TI  - Identification of a novel neutrophil membrane protein involved in modulation of
      oxidative burst.
AB  - On the basis of selective recognition by antibodies directed against neutrophil
      membrane determinants, a new neutrophil protein (molecular mass 82 kDa) has been
      identified, and shown to be functionally correlated with the oxidative response
      evoked in these cells by agonist stimulation. The protein is present in
      neutrophil membrane fraction but only upon activation it becomes accessible to
      recognition by a specific monoclonal antibody. In these conditions a complete and
      selective inhibition of O2- production occurs. The presence of a new protein
      antigen in neutrophil membranes linked to the activation of the O2- producing
      multienzyme complex that becomes external to the cell surface in primed or
      activated cells, might be important for future approaches aiming at the control
      of neutrophil response and at the identification of the activated forms of these
      cells.

PMID- 7522566
TI  - Anion transport function of mouse erythroid band 3 protein (AE1) does not require
      acylation of cysteine residue 861.
AB  - Cys-861 of mouse band 3 is equivalent to Cys-843 of human band 3, the only
      acylated cysteine residue in the anion exchanger AE1 of the red blood cell
      (Hamasaki et al. (1992) Progress Cell Res. 2, 65-71). Mutation of Cys-861 to
      serine or methionine caused no significant changes of band 3-mediated anion
      exchange as measured after expression of the appropriate cRNAs in Xenopus
      oocytes. Susceptibility to inhibition of transport by 4,4'-dinitrostilbene-2,2'
      disulfonate and PCMBS was not affected. We conclude that palmitoylation is not an
      absolute requirement for the successful execution the anion transport function by
      the hydrophobic domain of band 3 in the plasma membrane.

PMID- 7522567
TI  - Cloning and characterization of a glutamate transporter cDNA from human brain and
      pancreas.
AB  - L-Glutamate is the major excitatory neurotransmitter in the brain. Sufficient
      removal from the synaptic cleft after neurotransmission by the L-glutamate
      transport system is essential to prevent excitotoxicity and neurotoxicity. We
      isolated mRNA from human brain and pancreatic islet cells and screened for
      sequences of high homology to a previously characterized rat brain glutamate
      transporter. An isolated sequence (GLTR) shows a 87.5% and a 92.5% sequence
      similarity at the nucleotide and amino acid level, respectively, with a rat brain
      specific L-glutamate transporter but only a 65% homology to the recently cloned
      human glutamate/aspartate transporter. The human mRNA is differentially expressed
      in brain and to a lesser degree in pancreas and in fetal liver. The gene encoding
      for the newly identified cDNA is located on chromosome 5.

PMID- 7522568
TI  - Electrofusion of cell-size liposomes.
AB  - Cell size liposomes of egg phosphatidylcholine (PC), trans-acylated egg
      phosphatidylethanolamine (PE), bovine brain phosphatidylserine (PS) and egg
      phosphatidylglycerol, suspended in 2.5% of polyethylene glycol (M(r) 8000),
      Ficoll (M(r) 400,000) or Dextran (M(r) 71,200) were aligned by dielectrophoresis
      and fused by applying a 1.7 kV/cm pulse of varying duration. Because the internal
      and external media of liposome suspension can be controlled, and the surface
      charge is known, the results can be described mathematically. The fusion yields
      (FY) at different pulse length were measured by microscopy. The FY curves were
      sigmoidal, with a common minimally required pulse length of 19 microseconds, and
      shifted to longer pulse length with increasing external media conductivity or
      vesicle surface charge. The types of polymer in solutions had little effect. The
      minimal required pulse length was interpreted to be the minimum rise time for the
      smallest vesicle capable of reaching the bilayer breakdown potential induced by
      the pulse, and the sigmoidal shape FY curves represented the cumulative vesicle
      size distribution curve. The shifting of FY curves upon changing media
      conductivity or vesicle surface charge were quantitatively accounted for by the
      balance of pulse-induced dipole-dipole attraction and electrostatic repulsion.
      Deviation from sigmoidal shape FY curves in the cases of charged liposomes was
      explained by increasing electrostatic repulsion due to vesicle deformation under
      pulse-induced dipole pressure. The data confirm the hypothesis that membrane
      potential breakdown is a pre-requisite or minimum requirement for electrofusion,
      and support our earlier proposition that pulse-induced dipole force plays an
      important role in the electrofusion process, and that electrostatic repulsion
      posts additional barrier to electrofusion.

PMID- 7522569
TI  - Activation of the cystic fibrosis transmembrane regulator by cyclic AMP is not
      correlated with inhibition of endocytosis.
AB  - Based on the observation (Bradbury et al. (1992) Am. J. Physiol. 262, C752-C759)
      that conditions known to activate the cystic fibrosis transmembrane regulator
      protein (CFTR) increase the rate of exocytosis and decrease the rate of
      endocytosis, it was proposed that activation of the CFTR may involved cAMP
      dependent fusion of CFTR containing endosomes with the apical membrane. We have
      tested this hypothesis in two cell lines derived from epithelia that express
      defective chloride transport in cystic fibrosis (CF): the human colonic cell
      line, T84, and the tracheal cell line 9HTEo-. The dose-dependence of forskolin-
      and CPT-cAMP-induced inhibition of endocytosis were compared with the dose
      dependence of chloride channel activation. Endocytosis was determined from the
      uptake of FITC-dextran, and assayed in purified endosomes. Chloride channel
      activity was measured from the rate of I-efflux. If the fusion hypothesis is
      correct: (1) concentrations of agonist that inhibit endocytosis should activate
      chloride channel activity, and (2) the relationship between endocytosis and
      channel activation should be similar for forskolin and CPT-cAMP. Results in both
      cell lines were inconsistent with these postulates, suggesting that either
      chloride channel activation and the inhibition of endocytosis are separate
      effects of cAMP, or that the increase in apical CFTR resulting from agonist
      dependent inhibition of endosomal fusion is minimal.

PMID- 7522570
TI  - Can nitric oxide be spin trapped by nitrone and nitroso compounds?
AB  - Increasing interest in the study of nitric oxide (NO.) in many facets of
      biological research necessitates a search for accurate techniques to directly
      identify the free radical. One recently employed strategy for NO. detection is
      the method of electron spin resonance (ESR) used in combination with nitrone and
      nitroso spin traps. Applying this technique to our studies with nitric oxide
      synthase (NOS), we found that NO. generated directly from the enzyme system could
      not be detected. Further investigation revealed that 3,5-dibromo-4
      nitrosobenzenesulfonic acid (DBNBS) inhibited NO. generation by NOS at
      concentrations used for spin trapping. Reexamining the ability of various
      nitrones and DBNBS to spin trap authentic NO. dissolved in buffer, we obtained
      ESR spectra similar to those previously reported for the spin trap DBNBS.
      However, continuing our studies with 15NO. and N-hydroxylamine, we found these
      spectra to be artifactual. Our results emphasize the need to synthesize new spin
      traps, since currently available compounds are not capable of spin trapping NO.
      generated by NOS.

PMID- 7522571
TI  - Lipase of Pseudomonas cepacia for biotechnological purposes: purification,
      crystallization and characterization.
AB  - Commercial lipase (triacylglycerol lipase, EC 3.1.1.3) of Pseudomonas cepacia
      (Amano) has been purified to homogeneity by a single chromatography on phenyl
      Sepharose. The eluted lipase crystallized spontaneously at 4 degrees C in the
      eluent, containing 58-69% 2-propanol. The yield of the lipase was 87-100% and the
      specific activity during the hydrolysis of triolein 5800 U/mg protein. This
      protein has a molecular weight of 34.1 kDa as analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). Its purity was determined by SDS
      PAGE and capillary zone electrophoresis to be > or = 99%. Immobilization on
      Sepharose increased its stability in organic solvents. This lipase of P. cepacia
      differs from that of other Pseudomonas strains in respect to substrate
      specificity and during crystallization. It exhibits a high stability in organic
      solvents and supercritical carbon dioxide.

PMID- 7522572
TI  - Characterization of an RNase H deficient mutant of human immunodeficiency virus-1
      reverse transcriptase having an aspartate to asparagine change at position 498.
AB  - It has been proposed that Asp-443, Glu-478, and Asp-498 are important in RNase H
      mediated catalysis by human immunodeficiency virus-1 reverse transcriptase
      (Davies J.F., Hostomska, Z. Hostomsky, Z., Jordan, S.R. and Matthews, D.A. (1991)
      Science 251, 88-95; Mizrahi, V., Usdin, M.T., Harington, A. and Dudding, L.R.
      (1990) Nucleic Acids Res. 18, 5359-5363). Single point mutations at either
      position 443 (Mizrahi, V., Usdin, M.T., Harington, A. and Dudding, L.R. (1990)
      Nucleic Acids Res. 18, 5359-5363) or 478 (Schatz, O., Cromme, F.V., Gruninger
      Leitch, F. and Le Grice, S.F.J. (1989) FEBS Lett. 257, 311-314) severely inhibit
      RNase H activity but have only small effects on polymerase activity. We show here
      that a single mutation at position 498 of Asp to Asn (mutant D498N) results in a
      stable enzyme with a 20-fold reduction in the ratio of RNase H to polymerase
      activity. The mutant and wild type enzymes were equally processive, paused in the
      same locations, and extended primers at the same rate during DNA synthesis on a
      heteropolymeric RNA template. The rate of elongation on the homopolymeric
      template poly(rA) was also the same. The results indicate that the mutation does
      not affect normally measured catalytic parameters of the polymerase function of
      the enzyme. D498N catalyzed strand transfer synthesis on homopolymeric, but not
      heteropolymeric templates, indicating that RNase H activity is not required for
      the former activity, but is for the latter.

PMID- 7522573
TI  - Using linkers to investigate the spatial separation of the conserved nucleotides
      A9 and G12 in the hammerhead ribozyme.
AB  - Two series of hammerhead-derived ribozymes, or 'minizymes', in which helix II has
      been replaced by linkers of non-nucleotidic moieties, have been synthesised by
      solid-phase methods. In the first series, the minizymes had linkers containing
      one, two, three, four or five repeated units of phosphopropanediol, so that the
      number of atoms in the chain connecting the 3'O of the conserved A9 to the 5'O of
      the conserved G12 varied from 7 to 31. In the second, more-limited series, the
      minizymes contained linkers of either tetra- or hexa-ethyleneglycol. The rates at
      which these minizymes cleaved their cognate 13-nucleotide substrate were
      determined at 30 degrees C, and compared with the rates of cleavage by an
      analogous series of minizymes containing from two to six repeated units of
      thymine deoxyribonucleotide in place of helix II. In all three series, the
      cleavage rates increased with increasing linker length, with a plateau being
      reached at the longer lengths tested. Relative cleavage rates within the
      phosphopropanediol and the thymidine series depended strongly on linker length,
      but maximal activity was achieved in both series with 25 atoms in the chain
      joining A9 and G12. The lengths of linkers required to achieve maximal activity
      of the minizymes are considerably greater than the linkers of 13 atoms which are
      sufficient to stabilise the ends of double-helices of DNA or RNA.

PMID- 7522574
TI  - Tandem orientation of the inter-alpha-trypsin inhibitor heavy chain H1 and H3
      genes.
AB  - The inter-alpha-trypsin inhibitor H1 (ITIH1) and inter-alpha-trypsin inhibitor H3
      (ITIH3) genes have both previously been mapped to chromosomes 3 and 14 in the
      human and mouse, respectively. We now present evidence that these genes are
      physically linked. By using cDNA probes, a recombinant DNA phage has been
      isolated from a bacteriophage DNA library, which contains sequences flanking the
      5' end of the ITIH3 gene and the 3' end of the ITIH1 gene. Restriction
      endonuclease mapping, PCR analysis and DNA sequence determination of the
      recombinant phage and comparison to genomic DNA revealed that the genes are in
      tandem, 2721 base pairs apart, with the ITIH1 gene to the 5' side of the ITIH3
      gene. Their respective transcriptional units are thus on the same strand of DNA
      and most probably arose in evolution as the consequence of a duplication of a
      common ancestral gene.

PMID- 7522577
TI  - Structural characterization of modified nucleosides in tRNA hydrolysates by frit
      fast atom bombardment liquid chromatography/mass spectrometry.
AB  - Feasibility for the structural characterization of modified nucleosides in
      transfer RNA at low microgram levels has been investigated by using continuous
      flow frit-fast atom bombardment liquid chromatography/mass spectrometry (frit-FAB
      LC/MS). Sample of tRNA(Phe) from brewer's yeast (Saccharomyces cerevisiae) was
      used as a main model, and enzymatically hydrolysed by nuclease P1 and alkaline
      phosphatase. The resulting nucleoside mixture was separated by using a microbore
      reversed-phase LC column (150 mm x 0.5 mm i.d.) with an aqueous ammonium acetate
      methanol gradient, and the mass spectra were acquired on both positive and
      negative ionization modes. The modified nucleosides were characterized by
      comparison of the relative LC elution times with authentic nucleosides, and
      further confirmed by the structural information from the frit-FAB mass spectra
      where both molecular and base ions were in general observed as intense peaks in
      both ionization modes. Typically, 0.06-0.2 A260 units (3-10 micrograms) of
      isoaccepting tRNA was enough to obtain full-scan mass spectra of modified
      nucleosides, often occurring at a frequency of one per tRNA molecule using
      positive ion detection. The LC/MS system was used to screen modified nucleosides
      in tRNA of the extremely thermophilic microorganism Pyrodictium occultum.

PMID- 7522578
TI  - [Percutaneous drainage of intra-abdominal abscesses in Crohn disease].
AB  - The majority of abcesses associated with Crohn's disease require surgical
      treatment. Since the postoperative rate of complications is high, particular care
      is needed in the choice of surgical therapy for patients with Crohn's disease.
      The interventional radiological method of percutaneous abcess drainage provides
      the surgeon with an alternative technique suitable both for the curative
      treatment of simple abcesses and for the palliation of complicated abcesses prior
      to elective surgical treatment. We have retrospectively analysed the drainage
      protocols, operation reports, and case histories of 7 patients with intra
      abdominal abcesses in Crohn's disease. The results of our study emphasise the
      excellent clinical value of PAD in the treatment of abcesses associated with
      Crohn's disease.

PMID- 7522576
TI  - Role of superoxide dismutase and nitric oxide on the interaction between brain
      and systemic circulation during brain ischemia.
AB  - To elucidate the critical role of superoxide dismutase (SOD) and nitric oxide in
      brain injury and systemic circulation during brain ischemia, we performed
      bilateral carotid artery ligation (BCAL) on rats and evaluated the effects of NG
      monomethyl-L-arginine (L-NMMA) and a long-acting SOD derivative (SMA-SOD). After
      administration of L-NMMA, specific inhibitor against nitric oxide synthase (NOS),
      most of BCAL rats died within 6 h while no BCAL rats without L-NMMA died at all.
      Administration of SMA-SOD exhibited no effect on the life span of BCAL rats.
      Magnetic resonance imaging (MRI) and microscopic analysis for the ischemic brain
      revealed that, although administration of L-NMMA showed no significant effect on
      the ischemic brain of BCAL rats, SMA-SOD effectively prevented the ischemic
      changes based on permeability edema in the frontal lobe. Measurement of changes
      in the blood flow of the ischemic brain revealed that administration of L-NMMA
      decreased the blood flow in the BCAL rats while no remarkable changes were seen
      after administration of SMA-SOD. Urinary secretion of NO2-/NO3-, the metabolites
      of nitric oxide, was increased by challenging BCAL, and the presence of L-NMMA or
      SMA-SOD diminished this elevation. Blood pressure was increased by performing
      BCAL to rats, and administration of L-NMMA showed further elevation of the blood
      pressure. On the contrary, administration of SMA-SOD decreased post-ischemic
      hypertension. These results suggest that SOD may play a protective role for brain
      ischemia by suppressing increased vascular permeability, while nitric oxide
      showed beneficial effect on the ischemic brain by increasing the blood flow in
      the ischemic brain.

PMID- 7522579
TI  - The temporal relationships of synthesis and phosphorylation in stress proteins 70
      and 90 in aged caloric restricted rats exposed to bleomycin.
AB  - A single intraperitoneal injection of the human therapeutic drug bleomycin (BL)
      was administered to three groups of male Fischer 344 rats at time 0, and the
      incorporation of [35S]methionine ("synthesis") and phosphorylation patterns of
      stress proteins (sps/hsps) from bone marrow cells were analyzed over time by two
      dimensional electrophoresis and fluorography. Two groups of rats, young ad
      libitum (Y/AL--3 months) and old ad libitum (O/AL--28 months), had free access to
      rat chow, and a third group of old rats (O/CR--28 months) were maintained on a
      caloric restricted intake (60% of the AL diet). The administration of BL in Y/AL,
      O/AL and O/CR animals activated the 35S-labeling of sp 90 which reached a peak at
      4 hours. Labeling of sp 90 was significantly greater in Y/AL compared to O/AL,
      and the incorporation pattern of O/CR was intermediate to Y/AL and O/AL animals.
      All labeling of sp 90 in each group had disappeared by 10 hours after BL
      administration. Stress protein 70x (inducible form) in these three animal groups
      displayed a similar pattern of 35S-incorporation, but the amount of labeling was
      less than that of sp 90. No labeling of sp 70x remained by 13 hours after BL
      administration. Phosphorylation ([32P] phosphate incorporation) of sp 90 reached
      a maximum level at 2 hours in all animals, and 32P-labeling in Y/AL was
      significantly increased over O/AL and O/CR with an intermediate level found in
      O/CR animals. The turnover rate (phosphorylation/dephosphorylation) of sp 90
      induced by BL was significantly suppressed and temporarily extended in O/AL as
      compared with O/CR, which implied that CR not only increased incorporation of sp
      90, but also enhanced a utilization of the phosphate pool very similar to that
      seen in Y/AL animals.

PMID- 7522580
TI  - Three-dimensional protein models: insights into structure, function, and
      molecular interactions.

PMID- 7522575
TI  - Peptides related to thyrotrophin-releasing hormone (TRH) in human prostate and
      semen.
AB  - The TRH-related peptide, pGlu-Glu-ProNH2, which was first identified in rabbit
      prostate has recently been named fertilization-promoting peptide (FPP) because of
      its ability to enhance the in vitro fertilizing potential of mouse epididymal
      spermatozoa. This study set out to examine the nature of the TRH-related peptides
      in human prostate and semen but, first, the optimal conditions for collection of
      semen samples were investigated. FPP was degraded slowly (t1/2 = 163 min, S.E. +/
      51.3, n = 6) in seminal plasma which has allowed us to measure accurately the
      concentrations of FPP, after extraction of the peptide in acidified acetone
      precisely 5 min after ejaculation. In this way, high levels of FPP (mean: 49.5
      nmol/l) were detected in normal human semen, from young men, although other TRH
      related peptides did not appear to be present. We have also examined the TRH
      related peptides present in prostate samples from clinical patients both with and
      without evidence of benign prostatic hyperplasia (BPH), by ion-exchange
      chromatography followed by radioimmunoassay. Substantial concentrations of FPP
      were observed in normal (4.10 pmol/g tissue, S.E. +/- 1.46) and BPH prostate
      (6.27 pmol/g tissue, S.E. +/- 1.65). In addition, a second, neutral TRH
      immunoreactive peptide was always detected in BPH tissue (7.40 pmol/g tissue,
      S.E. +/- 1.98) with only low levels generally present in normal prostate. The
      possibility that the presence of high levels of the neutral peptide in prostate
      may be used as an indicator of the onset of BPH deserves further scrutiny.

PMID- 7522581
TI  - Three-dimensional model of the BR96 monoclonal antibody variable fragment.
AB  - Molecular modeling was used to build a three-dimensional model of the variable
      regions of the tumor-reactive monoclonal antibody BR96. An immunoconjugate of
      this antibody with the anticancer drug doxorubicin is currently in a phase I
      clinical trial for the treatment of solid tumors. A model structure of the BR96
      variable fragment was generated to guide site-specific mutagenesis experiments
      and further improve the affinity of the antibody. The model displayed a distinct
      groove-type binding site which contained a significant number of aromatic
      residues. The dimensions and nature of the proposed binding site were consistent
      with the binding of the Ley tetrasaccharide which was found to bind to BR96. On
      the basis of the model, some BR96 residues are proposed to be crucial for antigen
      binding. BR96 and its complex with the Ley determinant have recently been
      crystallized, and structure determination is currently underway. Therefore, the
      detailed prediction of the BR96 combining site will soon be assessed, as a "blind
      test", based on crystallographic data.

PMID- 7522582
TI  - Synthesis of a hybrid protein containing the iron-binding ligand of bleomycin and
      the DNA-binding domain of Hin.
AB  - The iron-binding and oxygen-activating domain of the natural product bleomycin
      [pyrimidoblamic acid-beta-hydroxy-L-histidine (PBA-beta-OH-His)] was attached to
      the NH2 terminus of the DNA binding domain of Hin recombinase (residues 139-190).
      This hybrid 54-residue protein PBA-beta-OH-His-Hin-(139-190) binds specifically
      to DNA at four distinct Hin binding sites with affinities comparable to those of
      the unmodified Hin(139-190). In the presence of dithiothreitol, Fe(II).PBA-beta
      OH-His-Hin-(139-190) cleaves DNA with specificity remarkably similar to that of
      Fe(II).EDTA-Hin(139-190). Analysis of the cleavage patterns suggests that site
      specific DNA cleavage is mediated by a localized diffusible species, in contrast
      with cleavage by bleomycin, which occurs through a nondiffusible oxidant. This
      has implications for the design of second-generation artificial sequence specific
      DNA cleaving proteins and defines limitations in current efforts to create atom
      specific chemistry on DNA.

PMID- 7522584
TI  - The chromatographic behaviour of cephalosporins in gel filtration chromatography,
      a novel method to separate high molecular weight impurities.
AB  - The interaction between cephalosporins and the dextran matrix of Sephadex gel in
      gel filtration chromatography has been thoroughly studied. Twelve cephalosporins
      with specific structures were examined under different chromatographic
      conditions, including 12 different mobile phases comprising inorganic or organic
      compounds of different charge or/and density of electrons on their negative ions,
      different types of Sephadex gel (Sephadex G-10 and Sephadex G-50) and different
      flow rates. It was found that the more negative the charge or/and density of
      electrons on the negative ions of buffer components, the more was the adsorption
      of cephalosporins on the solid phase; this indicated tht the mobile phase played
      an important role in gel filtration chromatography for cephalosporins. By choice
      of suitable chromatographic conditions, optimum separation of high molecular
      weight impurities from cephalosporins could be achieved. The novel method could
      be used as a routine method for the quality control of cephalosporin
      preparations.

PMID- 7522583
TI  - Fluorinated proteins as potential 19F magnetic resonance imaging and spectroscopy
      agents.
AB  - Fluorinated proteins have been synthesized and characterized as potential in vivo
      19F magnetic resonance imaging (MRI) and spectroscopy (MRS) agents. Proteins
      labeled with fluorine include bovine serum albumin, gamma-globulin, and purified
      immunoglobulin (IgG). The amino groups in proteins were selectively
      trifluoroacetylated using S-ethyl trifluorothioacetate to synthesize fluorinated
      proteins (TFA-protein; 1-3). In another approach, trifluoroacetamidosuccinic
      anhydride has been used to prepare corresponding fluorinated derivatives of
      proteins (TFASA-protein; 4-6). The fluorinated proteins have been purified by
      exhaustive dialysis and isolated in good yields (55-76%). The fluorinated
      proteins exhibit useful NMR characteristics and the biocompatibility for in vivo
      studies. The initial investigations demonstrate the potential of these new
      fluorinated proteins as in vivo MRI/MRS probes.

PMID- 7522585
TI  - Stability and in vitro metabolism of the mitogenic neuropeptide antagonists [D
      Arg1,D-Phe5, D-Trp7,9, Leu11]-substance P and [Arg6, D-Trp7,9, MePhe8]-substance
      P (6-11) characterized by high-performance liquid chromatography.
AB  - The substance P (SP) analogues [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-SP and [Arg6, D
      Trp7,9, MePhe8]-SP (6-11) (antagonists D and G, respectively) are under
      consideration as new anticancer drugs. In this report, the stability and in vitro
      metabolism of both antagonists in up to seven different media (water, 1 M acetic
      acid, human plasma, nude mouse liver and WX 322 human SCLC xenograft homogenized
      in either 1 M acetic acid or phosphate buffered saline (PBS), pH 7.4) have been
      characterized by both isocratic and gradient elution reversed-phase HPLC.
      Antagonist D was stable (never > 13% degradation over 24 h, at 37 degrees C) in
      water, 1 M acetic acid and plasma but was metabolized by PBS liver homogenates
      (10%, w/v) sequentially to two stable metabolites with a half life of 0.98 h at a
      concentration of 500 micrograms ml-1. The major pathway of degradation of
      antagonist G appeared to be C-terminal methionine oxidation (particularly in
      plasma) as well as hydrolysis, with even aqueous solutions being significantly
      affected at low concentrations of peptide (0.1 micrograms ml-1, half life 20.9 h
      at 37 degrees C). Stable metabolites of antagonist G were also detected in
      incubations with PBS liver homogenates (half life 1.53 h at 500 micrograms ml-1,
      37 degrees C). Overall, the data presented indicate that the modifications made
      to SP have been relatively successful in preserving chemical and biological
      stability.

PMID- 7522586
TI  - Developmental disabilities prevention and the distribution of risk among American
      Indians.
AB  - Selected risk factors for developmental disabilities demonstrate an apparent
      differential pattern of risk for American Indians as compared to the U.S. general
      population. Indian children appear to experience comparable or even lower rates
      of certain congenital anomalies which are associated with developmental
      disabilities and are difficult to prevent. Conversely, Indians are reported to
      experience higher rates of conditions which can be effectively targeted for
      prevention, including those related to prenatal exposure to alcohol, cigarette
      smoking, and maternal diabetes, as well as disabling sequelae of accidents and
      otitis media. Primary prevention is critical because of the long-term chronic
      nature of developmental disabilities and strategies focused on risk factors of
      particular relevance to Indian communities can achieve the greatest potential
      benefit.

PMID- 7522588
TI  - Simultaneous differential staining of cartilage and bone in rodent fetuses: an
      alcian blue and alizarin red S procedure without glacial acetic acid.
AB  - Differential staining of cartilage and bone has several applications including
      developmental toxicology studies of new chemical candidates for pharmaceutical,
      industrial, and environmental use. It has been more common to stain fetal bone
      only using the dye alizarin red S; however, failure to evaluate the cartilaginous
      portion of the skeleton may result in the failure to identify toxicologically
      important alterations in skeletal morphology. Previously, differential staining
      of fetal cartilage and bone was best achieved by combining alizarin red S for
      staining bone with alcian blue to stain cartilage in glacial acetic acid
      solution; however, occupational hazards posed by the use of glacial acetic acid
      make these methods undesirable. Replacement of the glacial acetic acid with
      potassium hydrogen phthalate eliminates these hazards without compromising the
      quality of the stained specimen.

PMID- 7522587
TI  - Differences between American Indian and non-Indian children referred for
      psychological services.
AB  - The physical and social characteristics of 60 American Indian children referred
      for psychological services were compared to those of 60 matched, non-Indian
      controls. Data were obtained from detailed records available in a
      multidisciplinary, medical school-related child study clinic. Indian children
      exhibited more health and social risk factors, but were superior to non-Indians
      on a variety of motor variables. Interpretations are offered concerning better
      psychological services for American Indian children based on better understanding
      of their possible exposure to physical health and social risks which may be
      related to psychological development.

PMID- 7522589
TI  - A rapid immunostaining method for frozen sections.
AB  - A simple and rapid one-step method for demonstrating immunohistochemical markers
      (leukocyte common antigen, cytokeratin, etc.) is described, which can help define
      the nature of poorly differentiated neoplasms for diagnosis using frozen section.
      Microwave irradiation was used to speed immunohistochemical analysis using
      "Enhanced Polymer One-step Staining" (EPOS) reagents on cryostat sections from a
      variety of pathologic samples. Reproducible results were obtained using EPOS
      reagents for leukocyte common antigen and cytokeratin. The overall procedure
      takes less than 10 min and can be completed during surgery.

PMID- 7522590
TI  - Pitfalls in the differentiation of N-glycosylation variants of prostate-specific
      antigen using concanavalin A.
AB  - We determined the optimal conditions for the separation of N-glycosylation
      variants of prostate-specific antigen using concanavalin A. Concanavalin A is a
      lectin that binds to the terminal sugar residues of glycoproteins. We
      demonstrated that differences in the percentage of prostate-specific antigen
      bound to concanavalin A-Sepharose in patients with benign prostatic hyperplasia
      compared with patients with prostatic carcinoma, as described in the literature,
      arise when insufficient concanavalin A binding sites are added for complete
      binding of the glycosylation variants of prostate-specific antigen. We observed
      similar percentages of prostate-specific antigen bound to concanavalin A
      Sepharose for benign prostatic hyperplasia (86.3% +/- 7.5, mean +/- SD) and
      carcinoma patients (81.8% +/- 12.0, mean +/- SD), when sufficient concanavalin A
      Sepharose was added to allow optimal binding, and when samples with high prostate
      specific antigen concentrations were not pre-diluted before incubation with
      concanavalin A-Sepharose. We conclude that differentiation of patients with
      benign prostatic hyperplasia or carcinoma of the prostate on the basis of
      differences in percentages of prostate-specific antigen bound to concanavalin A
      Sepharose, i.e. separation of N-glycosylation variants, is not possible.

PMID- 7522591
TI  - Differential steroidogenic response of subpopulations of porcine granulosa cells
      to insulin-like growth factor-1 (IGF-1) or IGF-1 analogs.
AB  - Two experiments were conducted to examine responses of porcine granulosa cells to
      insulin-like growth factor-1 (IGF-1) or IGF-1 analogs (des [1-3] and Long R3)
      that have reduced affinity for IGF-binding proteins (IGFBP). Both experiments
      evaluated estradiol and IGFBP production by granulosa cells after separation of
      cells into subpopulations that maintain long-term estradiol production in vitro
      (tightly bound) and those that do not (weakly associated). Granulosa cells were
      obtained from medium-sized follicles (4-6 mm) at random stages of the estrous
      cycle in experiment 1 and from the 10 largest follicles per ovary at 0 or 48 h
      after weaning in experiment 2. Follicle diameter and follicular fluid estradiol
      concentrations increased with time after weaning (p < 0.05). Tightly bound cells
      produced more estradiol than weakly associated cells at 24-120 h of culture in
      experiment 1 and from 0 to 48 h in experiment 2 (p < 0.05). In tightly bound but
      not weakly associated cells, IGF-1 stimulated estradiol production. The IGF
      analogs were more potent stimulators than IGF-1 in experiment 1 (p < 0.05); and
      in experiment 2, this response was restricted to cells collected at 48 h after
      weaning. Conversely, tightly bound cells obtained at 0 h after weaning responded
      similarly to IGF-1 and des (1-3). During the final 48 h of culture, weakly
      associated cells produced greater quantities of 28-30-kDa IGFBP than did tightly
      bound cells in response to IGF-1 or analogs (both experiments; p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522592
TI  - Ultrastructural characterization of endogenous retroviral particles isolated from
      normal human placentas.
AB  - Human placental endogenous retroviral (ERV) particle isolates were investigated
      by ultrastructural evaluation. Although retrovirus-like structures in normal
      human placental tissue sections have been described, the precise nature of these
      particles has not previously been defined. By direct electron microscopic (EM)
      observation of placental ERV isolates that display retroviral reverse
      transcriptase (RTase) activity and a buoyant density consistent with type-C
      retroviruses (1.17 g/ml on sucrose), we have shown these to contain particles
      with characteristic retroviral ultrastructural features. Samples were stained
      with 1.0% phosphotungstic acid (PTA), 0.5% uranyl acetate (UA), and low-angle
      shadowed with platinum/palladium. Isolated placental ERV particles have an
      apparent diameter of approximately 120 nm, are membrane-bound with a short
      surface fringe, and contain capsid particles (about 90 nm in diameter) within an
      internal matrix structure. These observations support the view that human
      placental cells normally express ERV particles.

PMID- 7522593
TI  - Novel culture procedure permitting the synthesis of proteins by rat calvarial
      cells cultured on hydroxyapatite particles to be quantified.
AB  - A simple culture procedure and assay conditions are described which have
      permitted us to quantify the synthesis of proteins which are associated with an
      osteoblastic phenotype, by rat calvarial periosteal cells grown on particulate
      materials. The main feature of the method is the use of an adhesive which does
      not permit cells to attach to itself but allows attachment and growth of cells on
      material particles embedded in it on glass coverslips. Cells were cultured for 27
      d on hydroxyapatite particle-coated coverslips. Alkaline phosphatase, osteopontin
      and collagen type I were monitored in cell lysates from d 10 to d 20. After
      Western blotting, osteopontin and collagen type I were quantified using specific
      antisera and enhanced chemiluminescence. Maximum levels coincided with peak
      alkaline phosphatase activity, after 10 and 17 d. The procedures described will
      be generally applicable to the comparison of cell behaviour on particulate
      substrata.

PMID- 7522594
TI  - Glyburide actions on the dihydropyridine-sensitive Ca2+ channel in rat vascular
      muscle.
AB  - The effects of glyburide, a purportedly selective ATP-sensitive K+ channel
      antagonist, were studied on dihydropyridine (DHP)-sensitive (L-type) Ca2+ channel
      currents in rat aortic muscle cells. Whole-cell voltage-clamp Ba2+ currents (IBa)
      were recorded at a series of test potentials (VT) from -30 to +60 mV during 300
      ms voltage steps from a holding potential of -80 mV. Bay k8644 (1 microM)
      increased peak divalent cation currents from 47.2 +/- 15.1 to 102.6 +/- 13.4 pA,
      and the current-voltage relationship curve was shifted 10 mV to the left (n = 5).
      The combination of 10 microM glyburide with 1 microM Bay k8644 further increased
      Bay k8644-enhanced IBa in each cell (average of 223.7 +/- 26.4 pA, n = 5), and
      caused a further 10 mV hyperpolarizing (leftward) shift of the activation curve.
      The kinetics of IBa were also changed (more rapid inactivation) by glyburide.
      These stimulatory actions of glyburide were reversed on washout. In contrast to
      this apparent synergism with Bay k8644, 10 microM glyburide alone inhibited
      (rather than potentiated) IBa by about 20% at VT of 0, +10, and +30 mV.
      Increasing glyburide concentration to 30 microM further inhibited the IBa to
      about 40-50% of controls. With the pure agonist isomer, 0.5 microM Bay R5417, at
      theoretically the same concentration of the minus enantiomer as is present in Bay
      k8644, IBa increased from 137 +/- 18.3 pA to 354.2 +/- 12.4 pA (n = 4).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7522595
TI  - Mechanism of the action of angiotensin-converting enzyme inhibitors on agonist
      induced Ca2+ influx.
AB  - To evaluate the direct effects of the angiotensin-converting enzyme (ACE)
      inhibitors, captopril, enalaprilat, enalapril (a prodrug without therapeutically
      significant ACE inhibitory effect) and ramiprilat, on cellular calcium
      metabolism, the cytosolic free calcium concentration was measured in cultured rat
      vascular smooth muscle cells using the fluorescent dye, fura-2. Preincubation
      with captopril, enalaprilat, enalapril, or ramiprilat for 40 min significantly
      reduced the angiotensin II-induced transplasma membrane calcium influx but did
      not influence the angiotension II-induced calcium release from internal stores.
      Captopril and ramiprilat also inhibited arginine vasopressin, but not the
      thapsigargin-, norepinephrine-, or the BayK 8644-induced changes in cytosolic
      calcium. Phorbol 12-myristate 13-acetate pretreatment for 30 s caused an increase
      in the angiotensin II-induced rise in cytosolic calcium. Although both captopril
      and verapamil reduced responses to angiotensin II to similar extents, only
      verapamil blocked the ability of phorbol 12-myristate 13-acetate to enhance
      responses to angiotensin II. It is concluded that ACE inhibitors modulate the
      effects of some but not all agonist-induced transplasma membrane calcium influx.

PMID- 7522598
TI  - Studies of cell pellets: II. Osmotic properties, electroporation, and related
      phenomena: membrane interactions.
AB  - Using the relations between pellet structure and electric properties derived from
      the preceding paper, the responses of rabbit erythrocyte pellets to osmotic or
      colloidal-osmotic effects from exchanged supernatants and from electroporation
      were investigated. Changing the ionic strength of the supernatant, or replacing
      it with dextran or poly(ethylene glycol) solutions, caused changes of Rp
      according to the osmotic behavior of the pellet. Rp was high and ohmic before
      electroporation, but dropped abruptly in the first few microseconds once the
      transmembrane voltage exceeded the membrane breakdown potential. After the
      initial drop, Rp increased as a result of the reduction of intercellular space.
      Rp increased regardless of whether the pellets were formed before or immediately
      after the pulse, indicating that porated cells experienced a slow colloidal
      osmotic swelling. The intercellular or intermembrane distances between cells in a
      pellet, as a function of osmotic, colloidal-osmotic, and centrifugal pressures
      used to compress rabbit erythrocyte pellets, were deduced from the Rp
      measurement. This offered a unique opportunity to measure the intermembrane
      repulsive force in a disordered system including living cells. Electrohemolysis
      of pelleted cells was reduced because of limited swelling by the compactness of
      the pellet. Electrofusion was observed when the applied voltage per pellet
      membrane exceeded the breakdown voltage. The fusion yield was independent of
      pulse length greater than 10 microseconds, because after the breakdown of
      membrane resistance, voltage drop across the pellet became insignificant.
      Replacing the supernatant with poly(ethylene glycol) or dextran solutions, or
      coating pellets with unporated cell layers reduced the colloidal-osmotic swelling
      and hemolysis, but also reduced the electrofusion yield. These manipulations can
      be explored to increase electroloading and electrofusion efficiencies.

PMID- 7522597
TI  - Improved technique for studying ion channels expressed in Xenopus oocytes,
      including fast superfusion.
AB  - The study of whole-cell currents from ion channels expressed in Xenopus oocytes
      with conventional two-electrode voltage clamp has two major limitations. First,
      the large diameter and spherical geometry of oocytes prevent extremely fast
      solution changes. Second, the internal medium is not controlled, which limits the
      experimental versatility of the oocyte expression system. For example, because
      the internal medium is not controlled, endogenous calcium-activated chloride
      conductances can contaminate currents measured with channels that are permeable
      to calcium. We describe a new technique that combines vaseline-gap voltage clamp
      for oocytes with a fast superfusion system. The vaseline-gap procedure is
      simplified by having the micropipette that monitors voltage serve a dual role as
      a perfusion micropipette that controls the internal solution. In addition, the
      technique provides fast external solution changes that are complete in 30-50 ms.
      We applied the approach to measure the calcium permeability of a muscle and a
      neuronal nicotinic acetylcholine receptor. Very fast agonist induced currents
      were measured without contamination by the secondary activation of calcium
      dependent chloride channels.

PMID- 7522596
TI  - Gap junction channels: distinct voltage-sensitive and -insensitive conductance
      states.
AB  - All mammalian gap junction channels are sensitive to the voltage difference
      imposed across the junctional membrane, and parameters of voltage sensitivity
      have been shown to vary according to the gap junction protein that is expressed.
      For connexin43, the major gap junction protein in the cardiovascular system, in
      the uterus, and between glial cells in brain, voltage clamp studies have shown
      that transjunctional voltages (Vj) exceeding +/- 50 mV reduce junctional
      conductance (gj). However, substantial gj remains at even very large Vj values;
      this residual voltage-insensitive conductance has been termed gmin. We have
      explored the mechanism underlying gmin using several cell types in which
      connexin43 is endogenously expressed as well as in communication-deficient
      hepatoma cells transfected with cDNA encoding human connexin43. For pairs of
      transfectants exhibiting series resistance-corrected maximal gj (gmax) values
      ranging from < 2 to > 90 nS, the ratio gmin/gmax was found to be relatively
      constant (about 0.4-0.5), indicating that the channels responsible for the
      voltage-sensitive and -insensitive components of gj are not independent. Single
      channel studies further revealed that different channel sizes comprise the
      voltage-sensitive and -insensitive components, and that the open times of the
      larger, more voltage-sensitive conductance events declined to values near zero at
      large voltages, despite the high gmin. We conclude that the voltage-insensitive
      component of gj is ascribable to a voltage-insensitive substate of connexin43
      channels rather than to the presence of multiple types of channels in the
      junctional membrane. These studies thus demonstrate that for certain gap junction
      channels, closure in response to specific stimuli may be graded, rather than all
      or-none.

PMID- 7522599
TI  - Simulation of integrin-cytoskeletal interactions in migrating fibroblasts.
AB  - Cell migration is a dynamic phenomenon requiring a physical interaction between
      the internal cell motile machinery and the external substratum in which adhesion
      receptors, such as integrins, serve as the transmembrane link. To analyze
      quantitatively this interaction, we apply a modified Brownian dynamics algorithm
      to simulate cytoskeleton-mediated transport of integrin on the dorsal surfaces of
      migrating fibroblasts. Previously, we experimentally demonstrated that integrin
      is transported in an intermittent fashion, with directed excursions interspersed
      by diffusive periods, preferentially toward the cell edge where the integrin is
      likely used in the formation of nascent adhesions. Integrins containing mutations
      in the cytoskeleton-binding region of the cytoplasmic domain display
      statistically different degrees of directed transport, indicating that this
      phenomenon is dependent on cytoskeletal associations. In the present work, we
      develop a computer algorithm generating simulated integrin transport
      trajectories, given estimates for the rate constants defining coupling (kc) and
      uncoupling (ku) of integrin with cytoskeletal components. Other parameters
      supplied to the program, the diffusion coefficient (D) for integrin in the
      membrane and the instantaneous velocity (vi) of the integrin/cytoskeleton
      complex, have been measured independently in our experimental system. By
      comparing the simulated trajectories with those obtained experimentally, we are
      able to estimate the coupling and uncoupling rate constants for the interaction
      of integrin with cytoskeletal elements in vivo. We find that integrin couples
      with cytoskeletal elements at a rate approximately 10 times slower than its rate
      of uncoupling (kc = 0.3 s-1, ku = 3 s-1). Comparison of these rate constants with
      an equivalent rate constant for diffusion, k+ = 0.4 s-1, indicates that the
      coupling interaction is likely a diffusion-limited process, as is typically
      expected for membrane processes. We further show by calculation that directed
      transport is necessary for integrin to traverse the length of an extending
      lamellipod to its leading edge; diffusion alone is not sufficiently fast to
      supply adhesion receptors to points of new cell/substratum contact.

PMID- 7522601
TI  - GROPAP--a new staining method.

PMID- 7522600
TI  - A view of thermodynamics of hydration emerging from continuum studies.
AB  - Main physical-chemical features of hydration found in continuum studies and
      possible limitations of the method are analyzed. Particular attention is given
      to: the choice of thermodynamic observables to be compared to the calculations;
      representations of the solute polarizability; compensation between the loss of
      hydration enthalpy and gain in Coulomb interactions upon a complex formation; two
      minima in interaction potentials between polar groups in solution; similarities
      and dissimilarities between interaction potentials in solution from continuum and
      molecular theories; continuum calculations of entropies of hydration; and
      evaluation of a temperature dependence of thermodynamic characteristics of
      hydration with continuum methods.

PMID- 7522602
TI  - Changes in the level of blood suppressor CD8+CD57+ lymphocytes, when HIV-1 p24
      antigen reappears in the blood.
AB  - Using the marker Leu2 + Leu7 + to detect the CD8 suppressor cells (CD88+CD57+),
      we have observed that their blood level, which increases after primoinfection,
      during the latent period, increases still further just before and when the p24
      antigen returns and is present in the blood. Its ratio over cytotoxic CD8+ cells
      remains high during the AIDS period, though the absolute number decreases.

PMID- 7522605
TI  - Platelet derived wound healing factors (PDWHF) accelerate and augment wound
      healing angiogenesis in the rat.
AB  - The object of this study was to determine the effect of PDWHF on wound healing
      angiogenesis. Sponges saturated with PDWHF were implanted in rats. Six hours to
      14 days post-implantation, vascular corrosion casts were prepared and examined by
      SEM. Leukocyte margination and angiogenesis was accelerated by 24-48 hours.
      Vessel number was also greater than in the controls. Another series of PDWHF
      treated sponges were implanted. Fourteen days later the vasculature was perfused
      with Evans blue. Sponges were homogenized, and absorbance of the supernatants was
      determined. Absorbances of PDWHF supernatants was 2X greater than controls. PDWHF
      enhanced wound healing angiogenesis in the rat.

PMID- 7522604
TI  - Compositional frequencies of amino acids in the proteins and the genetic code.
AB  - It was found that amino acid compositional frequencies in proteins demonstrate a
      pseudosymmetry pattern in respect of the genetic code arrangement as we discussed
      in earlier papers (Siemion and Stefanowicz, 1992a, BioSystems, 27, 77-84; Siemion
      and Stefanowicz, 1992b, Bull. Pol. Acad. Sci., Chem. 40, 11-20; Siemion, 1994,
      BioSystems, 32, 25-35). The type of pseudosymmetry observed is very similar to
      that found in the changes of Chou-Fasman P alpha conformational parameters within
      the genetic code arrangement. It is also shown that the compositional frequencies
      of amino acids belonging to the 'G' and 'C' families of codons (excluding UCN Ser
      codons) change linearly with the sequence of the one-step mutations expected by
      our arrangement of proper codons.

PMID- 7522603
TI  - Lovastatin inhibits HIV-1 expression in H9 human T lymphocytes cultured in
      cholesterol-poor medium.
AB  - The effects of the HMG-Coenzyme A reductase inhibitor lovastatin on HIV-1
      expression and sterol synthesis have been investigated in the human H9
      lymphocytic cell line. To this purpose, sterol synthesis from 14C-acetate, cell
      multiplication and reverse transcriptase activity have been measured in parallel
      at various times after cell infection by HIV-1. It was found that nine days after
      viral loading, lovastatin inhibited both sterol synthesis and viral
      multiplication as assessed by the reverse transcriptase activity. Since HIV
      infection has been shown to induce alterations in membrane cholesterol content,
      suggesting that the virus cycle may be partially dependent upon cellular
      cholesterol, inhibitors of cholesterol synthesis could be an interesting way of
      research in order to slower HIV propagation.

PMID- 7522610
TI  - Over-expression of MBP and PLP messenger RNA in 8-day-old trembler brain.
AB  - The trembler mouse suffers from a dominantly inherited mutation of the peripheral
      myelin protein 22 (PMP-22) gene which results in abnormal myelination of the
      peripheral nervous system. However, the clinical symptoms observed in the mutant
      suggest abnormalities in the central nervous system. Using the Northern blot
      technique, we investigated the steady-state levels of mRNA encoding myelin
      protein genes in 8-day-old normal and trembler brains. We measured a two- to four
      fold increase for myelin basic protein (MBP) and proteolipid protein (PLP) mRNAS
      in the trembler samples. Whether a relationship exists between this observation
      and the onset of the clinical symptoms is still to be determined.

PMID- 7522608
TI  - Co-existence of PACAP and nitric oxide synthase in the rat hypothalamus.
AB  - The possible co-existence of pituitary adenylate cyclase-activating polypeptide
      (PACAP)-38 and nitric oxide synthase (NOS) in the rat hypothalamus was examined
      by a combination of PACAP-immunocytochemistry and NADPH-diaphorase
      histochemistry. Virtually all PACAP-38-immunoreactive neurones in the
      paraventricular and supraoptic nuclei exhibited NADPH-diaphorase activity. Since
      NADPH-diaphorase activity was identical to NOS-immunoreactivity in the
      magnocellular neurosecretory neurones, this finding indicates that the PACAP
      neurones synthesize NO.

PMID- 7522607
TI  - Expression of gp330 and gp330/alpha 2-macroglobulin receptor-associated protein
      in renal tubular differentiation.
AB  - The gp330/alpha 2-macroglobulin receptor-associated protein (RAP) is a 39- to 45
      kd protein that binds to the low-density lipoprotein receptor-related
      protein/alpha 2-macroglobulin receptor and to gp330, a major glycoprotein of the
      brush border of proximal tubule cells. Despite evidence that gp330 functions as a
      receptor for several ligands and that soluble RAP inhibits ligand binding to
      gp330 in vitro, the physiologic function of RAP is unknown. Given the predominant
      location of RAP within the rough endoplasmic reticulum (RER), RAP might be
      involved in the intracellular processing and/or transport of gp330. The
      developing rat kidney was used as a dynamic model to study in detail the
      relationship between gp330 and RAP in vivo by immunohistochemical techniques. RAP
      was expressed in the renal vesicle and continued to be present, with a vesicular
      and perinuclear pattern of staining, in both proximal tubule cells and glomerular
      cells at subsequent stages. Immunoperoxidase electron microscopy demonstrated RAP
      in cisternae of the RER and in large subapical vesicles. gp330 was initially
      expressed in early proximal tubule cells in S-shaped bodies and was located in
      the perinuclear envelope and cytoplasmic vesicles as well as at the apical
      surface. Cytoplasmic gp330 staining was more evident at a stage subsequent to the
      S-shaped body, possibly related to more active biosynthesis. By comparative
      analysis of the patterns of immunofluorescence and immunoperoxidase staining,
      gp330 and RAP colocalized in the RER and in some large subapical vacuoles, but no
      definite RAP staining could be detected at the surface of proximal tubule cells
      at any stage, despite the presence of abundant gp330 in this location. The
      expression of gp330 at the apical surface of immature tubular cells was
      associated with the onset of fluid-phase endocytosis of fluoroscein
      isothiocyanate-dextran and, therefore, of reabsorption of material from the
      tubular lumen, in the absence of concomitant changes in RAP expression in the
      same cells. These findings indicate that the role of endogenous RAP may not be
      directly related to ligand binding of gp330 at the surface of proximal tubule
      cells, although RAP may be involved in the processing and the intracellular
      trafficking of newly synthesized gp330, in particular in the delivery of gp330 to
      the plasma membrane.

PMID- 7522609
TI  - Ligand- and voltage-gated ion channels are expressed by embryonic mouse retinal
      neurones.
AB  - The present study was intended to investigate whether voltage- and ligand
      activated ion channels are expressed during prenatal development by neurones
      located in the ganglion cell layer of the mammalian retina. Whole cell patch
      clamp recordings from presumed mouse retinal ganglion cells revealed the
      expression of Na+, K+ and Ca2+ channels, predominantly of the low-voltage
      activated type. Using local application of transmitter substances we further
      demonstrated that these cells are endowed with glutamate receptors of the N
      methyl-D-aspartate (NMDA) and non-NMDA type as well as nicotinic acetylcholine,
      gamma-amino-butyric acid (GABA)A and glycine receptors. Voltage-gated
      conductances probably underlie spontaneous action potential generation by
      embryonic ganglion cells. The early expression of transmitter-gated ion channels
      indicates important functions of these channels in cell differentiation
      processes.

PMID- 7522606
TI  - Suppression of in vivo tumor-induced angiogenesis by the protein-bound
      polysaccharide PSK.
AB  - The anti-angiogenic effects of an antitumor protein-bound polysaccharide, PSK,
      obtained from cultured mycelia of Coriolus versicolor in basidiomycetes were
      examined by the mouse dorsal air sac assay. PSK suppressed the mouse hepatoma
      MH134-induced angiogenesis when assessed by morphological and biochemical
      examinations. This finding suggested that the anti-metastatic effect of PSK is
      attributed to the suppression of tumor-induced angiogenesis.

PMID- 7522611
TI  - 5-HT2A receptor-mediated outward current in C6 glioma cells is mimicked by
      intracellular IP3 release.
AB  - The C6 glioma cell line possesses 5-HT2A receptors that have been shown to
      increase intracellular calcium levels. We have studied the electrophysiological
      response of these cells to 5-HT using the whole-cell recording method. Under
      voltage-clamp, 5-hydroxytryptamine (5-HT) produced an outward current in these
      cells which was inhibited by extracellularly applied ketanserin and spiperone and
      by EGTA (10 mM) in the recording electrode. The 5-HT induced response could be
      mimicked by intracellular photolytic release of inositol (1,4,5) trisphosphate
      (IP3) from caged molecules. The reversal potentials for the IP3- and 5-HT-induced
      responses were closely matched. The data indicates that the outward current is
      likely to be mediated by 5-HT2A receptors stimulating IP3 production which
      increases intracellular calcium leading to the opening of calcium-activated
      potassium channels.

PMID- 7522612
TI  - Expression of neuropeptides in the rat mesencephalic trigeminal nucleus after
      peripheral axotomy.
AB  - Certain populations of dorsal root ganglion cells upregulate galanin (GAL) and
      neuropeptide Y (NPY) after peripheral axotomy. Less is known of the functional
      properties of the neurones reacting in this way. The primary sensory
      mesencephalic trigeminal (Me5) neurones are considered to have purely
      proprioceptive functions. In this study immunohistochemistry and in situ
      hybridization have been used to investigate the expression of NPY and GAL in Me5
      neurones after peripheral axotomy. Both methods revealed a transient upregulation
      of GAL and NPY in Me5 neurones which was first observed 3 days postoperatively,
      peaking at 1 and 2 weeks and then being reduced. The results show that
      proprioceptive neurones may upregulate these peptides as a consequence of injury.

PMID- 7522613
TI  - Nitric oxide synthase-immunoreactive cells in the CNS and periphery of Lymnaea.
AB  - The presence and distribution of nitric oxide synthase (NOS) in the CNS and
      peripheral organs (buccal muscles, oesophagus, salivary glands, foot, mantle and
      pneumostome) of the pulmonate mollusc, Lymnaea stagnalis were studied using an
      antiserum developed against rat cerebellar NOS. NOS-immunopositive neurones in
      Lymnaea were localized predominantly in the buccal ganglia as well as in distinct
      areas of the cerebral and suboesophageal ganglia. NOS-immunoreactive terminals
      were also found on the somata of some central neurones. In the periphery, NOS
      immunostaining was detected only in a few neurones in the pneumostome area and in
      the osphradial ganglion. In addition, approximately 100 NOS-immunopositive cells
      have been found in the salivary glands. Our data supports other recent reports
      indicating that NO may be a signal molecule in the CNS of molluscs.

PMID- 7522614
TI  - Tyrosine phosphorylation in rat spinal cord after sciatic nerve transection.
AB  - Immunocytochemistry using antibodies against phosphotyrosine was employed to
      identify changes in tyrosine phosphorylation in the rat spinal cord consequent to
      sciatic nerve injury. Increased immunostaining in the spinal gray matter, dorsal
      columns and gracile nucleus on the side of the lesion became evident after 3 days
      and was more pronounced with longer survival times up to 3 weeks (the longest
      survival tested). This increase was most prominent in the fourth lumbar segment
      (the focus of termination of sciatic nerve afferents). Immunostaining was ain
      astroglial cells and their processes in the dorsal horn; stained microglia were
      also seen. Immunopositivity also increased in glial cells surrounding motoneurons
      at the same levels. These changes suggest that a diffusible growth factor
      released centrally by injured nerve fibers activates tyrosine phosphorylation in
      glial cells via receptor tyrosine kinases.

PMID- 7522617
TI  - Deleterious effects of high dose gamma-globulin therapy on patients with
      hemophagocytic syndrome.

PMID- 7522618
TI  - [Protective effect of the lysosomotrophic preparation rheopolyglucin in treating
      iron-deficient anemia with iron saccharate].

PMID- 7522616
TI  - Combination chemotherapy with COP-BLAM III for intermediate and high-grade non
      Hodgkin's lymphoma.
AB  - The clinical effects of COP-BLAM III combination chemotherapy and recombinant
      human granulocyte colony-stimulating factor (rhG-CSF) were examined in 60
      patients with intermediate or high-grade non-Hodgkin's lymphoma (NHL). The
      patients consisted of 37 men and 23 women with a median age of 53 years. The
      modified COP-BLAM III regimen based on the method of Boyd et al. consisted of six
      cycles of 6 weeks duration each. The complete remission rate for all patients was
      83.3% (50 of 60 patients). With the median observation duration of 47.5 months,
      the overall median survival time for all patients was 86 months or more. The
      disease-free survival rate for the 50 CR patients was 88.2% at 86 months. The
      incidence of infections was significantly reduced by the concomitant use of rhG
      CSF. The most common adverse effect was neutropenia (< or = 1000/microliters).
      The percent diffusing capacity for carbon monoxide in the lung (%DLCO) was
      reduced in 12 of the 60 patients (20.0%). We conclude that COP-BLAM III is a
      useful regimen for intermediate and high-grade NHL. However, caution is required
      since some elderly patients had reduced pulmonary function.

PMID- 7522620
TI  - [Involvement of fibronectin and serum components interacting with it in
      regulating the activity of human natural killer cells].

PMID- 7522619
TI  - [The effect of substance P on catecholamine level and activity of enzymes for
      their synthesis in the brain of chronically alcoholized rats].

PMID- 7522621
TI  - Leukocyte-endothelial adhesion molecules.
AB  - In the 9 years since the last review on leukocyte and endothelial interactions
      was published in this journal many of the critical structures involved in
      leukocyte adherence to and migration across endothelium have been elucidated.
      With the advent of cell and molecular biology approaches, investigations have
      progressed from the early descriptions by intravital microscopy and histology, to
      functional and immunologic characterization of adhesion molecules, and now to the
      development of genetically deficient animals and the first phase I trial of "anti
      adhesion" therapy in humans. The molecular cloning and definition of the adhesive
      functions of the leukocyte integrins, endothelial members of the Ig gene
      superfamily, and the selectins has already provided sufficient information to
      construct an operative paradigm of the molecular basis of leukocyte emigration.
      The regulation of these adhesion molecules by chemoattractants, cytokines, or
      chemokines, and the interrelationships of adhesion pathways need to be examined
      in vitro and, particularly, in vivo. Additional studies are required to dissect
      the contribution of the individual adhesion molecules to leukocyte emigration in
      various models of inflammation or immune reaction. Certainly, new adhesion
      structures will be identified, and the current paradigm of leukocyte emigration
      will be refined. The promise of new insights into the biology and pathology of
      the inflammatory and immune response, and the potential for new therapies for a
      wide variety of diseases assures that this will continue to be an exciting area
      of investigation.

PMID- 7522615
TI  - Binding of heparan sulfate glycosaminoglycan to beta-amyloid peptide: inhibition
      by potentially therapeutic polysulfated compounds.
AB  - Heparin sulfate proteoglycans are believed to play an important role in
      amyloidosis as pathologic chaperones. They bind to amyloidogenic proteins and may
      mediate the deposition and fibrillogenesis of amyloid at specific tissue sites.
      In the present study, we demonstrate that heparin sulfate glycosaminoglycan and
      proteoglycan both bind to the beta-amyloid peptide involved in Alzheimer's
      disease. The interaction of heparan sulfate proteoglycan and glycosaminoglycan
      can be inhibited by other sulfated compounds such as heparin, dextran sulfate and
      pentosan polysulfate. These polysaccharides which are currently used clinically,
      their derivatives or analogs may be effective as therapeutic agents to prevent or
      slow the progression of amyloidogenesis in Alzheimer's disease or other
      amyloidogenic disorders.

PMID- 7522622
TI  - Protein-tyrosine kinase p72syk in Fc gamma RI receptor signaling.
AB  - In this report we show that gamma-interferon (IFN) induces the expression of the
      nonreceptor protein tyrosine kinase, p72syk, and that cross-linking the Fc gamma
      RI receptor in IFN-differentiated U937 cells (U937IF cells) results in the
      activation of syk kinase. We show that syk is tyrosine phosphorylated (12-fold
      increase) after Fc gamma RI cross-linking. In vitro kinase assays demonstrate
      that the specific kinase activity of syk increased eightfold after Fc gamma RI
      cross-linking. The activation of signal transduction through the Fc gamma RI
      receptor, as measured by the respiratory burst, is associated with the tyrosine
      phosphorylation and catalytic activation of the syk kinase. We show that syk
      coprecipitates with the gamma subunit of the Fc gamma RI, Fc gamma RI gamma. The
      data suggest that p72syk is involved in signal transduction through the Fc gamma
      RI receptor, involving the Fc gamma RI gamma subunit.

PMID- 7522623
TI  - Human interleukin-4 enhances stromal cell-dependent hematopoiesis: costimulation
      with stem cell factor.
AB  - Interleukin-4 (IL-4) has distinct hematopoietic activities, primarily as a
      costimulant with other cytokines to enhance colony formation of hematopoietic
      progenitors. We investigated the influence of IL-4 on stromal cell-supported long
      term cultures (LTCs) of normal human bone marrow. Addition of IL-4 to LTCs of
      unseparated bone marrow or highly enriched CD34+ cells resulted in a significant
      increase of myeloid progenitors in the nonadherent, as well as in the stromal
      cell-adherent cell populations. In contrast, the total cell number was not
      influenced by IL-4, suggesting a selective effect on primitive progenitor cells.
      Cord blood cells or CD34+ bone marrow cells were incubated with stem cell factor
      (SCF) and/or IL-4 in stromal cell-free cultures. In these experiments, a twofold
      to fivefold increase of myeloid progenitor cells was observed in the presence of
      SCF and IL-4 as compared with SCF alone. Preincubation of the stromal cell
      cultures with IL-4 resulted in an enhanced adherence of CD34+ cells to the
      stromal layer. Secretion of hematopoietic growth factors produced by the stromal
      cells, such as granulocyte-macrophage colony-stimulating factor (G-CSF), and IL
      1, was inhibited by IL-4. Thus, the increase of hematopoietic progenitors in
      LTCs, as observed in the presence of IL-4, can be at least partially explained by
      a costimulation of SCF and IL-4 on primitive progenitor cells and by an
      enhancement of hematopoietic cells to stroma. The downregulation of CSFs by IL-4
      might prevent the expansion of the mature hematopoietic cell compartment.

PMID- 7522624
TI  - Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the
      possible relevance for Hodgkin's disease.
AB  - CD40 was originally described as a B-cell-restricted antigen and was subsequently
      found to be a member of the tumor necrosis factor (TNF) receptor superfamily.
      CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some
      carcinoma cell lines, and plays a critical role in cell contact-dependent
      activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the
      presumed malignant cells of Hodgkin's disease (HD); were found to express high
      levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L)
      induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin
      alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play
      a significant role in the clinical presentation and pathology of HD, a tumor of
      cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell
      lines. In contrast, CD40L enhanced expression of costimulatory molecules
      intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which
      are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60%
      reduction of the expression of the HD-associated CD30 antigen, another member of
      the TNF receptor superfamily. Primary and cultured H-RS cells express not only
      CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and
      the CD40-CD40L interaction might be a critical element in the deregulated
      cytokine network and cell contact-dependent activation cascade typical for HD.

PMID- 7522627
TI  - Inhibition of nitric oxide production is associated with enhanced weight loss,
      decreased survival, and impaired alloengraftment in mice undergoing graft-versus
      host disease after bone marrow transplantation.
AB  - The pathophysiologic role of nitric oxide (NO) in graft-versus-host disease
      (GVHD) was investigated in a murine bone marrow (BM) transplantation model where
      donor and recipient were H-2-matched but differed at multiple minor
      histocompatibility antigens. Host AKR/J (H-2K) mice received lethal total body
      irradiation as pretransplant conditioning followed by transplantation of donor
      B10.BR (H-2K) BM cells with or without spleen cells as a source of GVH-reactive T
      cells. NO production, as assessed by serum nitrate and nitrite levels, was
      increased for up to 3 weeks posttransplant in animals undergoing both moderate
      and severe GVHD. Administration of NG-methyl-L-arginine (L-NMA), an inhibitor of
      nitric oxide synthase, to animals undergoing GVHD resulted in effective
      suppression of NO production when compared with saline-treated GVHD control
      animals. Suppression of NO production by L-NMA in GVHD animals was associated
      with enhanced weight loss early posttransplant and decreased overall survival.
      Histologic analysis of tissues from L-NMA-treated and saline-treated GVHD animals
      showed that early weight loss was not because of an exacerbation of GVHD,
      indicating that NO did not appear to play an immunosuppressive role in this
      experimental model. L-NMA-treated animals with enhanced weight loss were observed
      to have splenic atrophy, decreased extramedullary hematopoiesis, and a reduction
      in BM cellularity when compared with GVHD control mice that were weight-matched
      before transplant. Analysis of T-cell chimerism in the spleen showed that L-NMA
      treatment impaired donor T-cell repopulation. In vitro colony-forming unit (CFU)
      assays were performed to further assess the role of NO on BM progenitor cell
      growth. L-NMA added directly into culture had no effect on CFU
      granulocyte/macrophage (CFU-GM) formation in normal murine BM. In contrast, total
      CFU-GM from L-NMA-treated animals were significantly reduced when compared with
      GVHD controls or BM control animals who did not develop GVHD. Collectively, these
      data indicate that inhibition of NO impairs hematopoietic reconstitution and
      support the premise that NO appears to play a novel role in the facilitation of
      alloengraftment posttransplant.

PMID- 7522625
TI  - CD3+, CD56+ aggressive variant of large granular lymphocyte leukemia.
AB  - Clonal expansions of CD3+ large granular lymphocytes (LGL) have been classified
      as T-LGL leukemia. The majority of patients with T-LGL leukemia have a chronic
      disease (years) manifested often by severe neutropenia, rheumatoid arthritis, and
      mild-to-moderate splenomegaly. The characteristic phenotype of the leukemic LGL
      is CD3+, CD8+, CD16+, CD57+, and CD56-. In this report we describe an aggressive
      variant of T-LGL leukemia in which leukemic LGL also expressed CD56, as
      identified by two-color flow-cytometry analysis. In contrast to the chronic
      nature typical of T-LGL leukemia, these patients presented with a severe systemic
      illness that was rapidly progressive and resistant to treatment. Atypical
      clinical features included rapidly increasing spleen size to massive proportions,
      extensive lymphadenopathy, and the presence of B symptoms (fever, nightsweats,
      weight loss). Hematologic and pathologic features were also unusual for T-LGL
      leukemia. These patients had very high LGL counts at diagnosis (range 11,692 to
      26,312 microL), which increased rapidly despite treatment. Histopathologic
      examination of splenic sections showed extensive infiltration of red pulp cords
      and sinuses by leukemic cells with atrophy of the white pulp. These
      clinicopathologic features are similar to those described for patients with
      natural killer cell (NK)-LGL leukemia, whose cells are also CD56+. However,
      unlike NK-LGL leukemia, we could not show a direct pathogenic role for Epstein
      Barr virus (EBV), as Southern-blot analyses using an EBV-joined termini probe
      were negative in these patients. Our findings suggest that CD3+, CD56+ LGL
      leukemia is a distinct clinicopathologic entity separate from the usual CD3+,
      CD56- T-LGL leukemia. The expression on leukemic LGL of CD56, an adhesion
      molecule, may determine the aggressive biologic nature of this newly described
      disease.

PMID- 7522628
TI  - A review of 125 cases to determine the risk of myelodysplasia and leukemia in
      pediatric neutropenic patients after treatment with recombinant human granulocyte
      colony-stimulating factor.

PMID- 7522626
TI  - Inhibition of leukocyte L-selectin function with a monoclonal antibody attenuates
      reperfusion injury to the rabbit ear.
AB  - The leukocyte adhesion molecule L-selectin mediates neutrophil adhesive
      interactions with endothelial cells and is in part responsible for neutrophil
      rolling. We examined the role of L-selectin in ischemia-reperfusion injury of
      rabbit ears using a monoclonal antibody (MoAb) directed to a functional epitope
      of L-selectin. Arterial blood flow to the rabbit ear was occluded for six hours
      with ambient temperature at 23 degrees C to 24 degrees C. Rabbits were treated at
      reperfusion with saline (n = 8), the L-selectin function-blocking LAM1-3 MoAb (2
      mg/kg), or the nonfunction-blocking LAM1-14 MoAb (2 mg/kg). Tissue injury was
      determined by measuring edema and necrosis. Edema in the LAM1-3 MoAb-treated
      group (peak = 25 +/- 4 mL) was significantly less (P < .05) than in saline
      treated (peak = 40 +/- 8 mL) and LAM1-14 MoAb-treated (peak = 41 +/- 6 mL)
      groups. Tissue necrosis at 7 days was not observed in the LAM1-3 MoAb-treated
      group, whereas significant necrosis (P < .05) was seen in the saline- (8% +/- 3%
      necrosis) and LAM1-14 MoAb-treated (7% +/- 3% necrosis) group. We conclude that
      blocking L-selectin ameliorates necrosis and edema after ischemia and reperfusion
      in the rabbit ear, presumably by blocking neutrophil rolling.

PMID- 7522629
TI  - Phase I clinical trial using escalating single-dose infusion of chimeric anti
      CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma.
AB  - The B-cell antigen CD20 is expressed on normal B cells and by nearly all B-cell
      lymphomas. This nonmodulating antigen provides an excellent target for antibody
      directed therapies. A chimeric anti-CD20 antibody (IDEC-C2B8), consisting of
      human IgG1-kappa constant regions and variable regions from the murine monoclonal
      anti-CD20 antibody IDEC-2B8, has been produced for clinical trials. It lyses
      CD20+ cells in vitro via complement and antibody-dependent cell-mediated lysis.
      Preclinical studies have shown that the chimeric antibody selectively depletes B
      cells in blood and lymph nodes in macaque monkeys. In this phase I clinical
      trial, 15 patients (3 per dose level) with relapsed low-grade B-cell lymphoma
      were treated with a single dose (10, 50, 100, 250, or 500 mg/m2) of antibody
      administered intravenously. Treatment-related symptoms correlated with the number
      of circulating CD20 cells and grade II events consisted of fever (5 patients);
      nausea (2), rigor (2), orthostatic hypotension (2), bronchospasm (1), and
      thrombocytopenia (1). No significant toxicities were observed during the 3 months
      of follow-up. Serum C3, IgG, and IgM levels, neutrophils, and T cells were
      largely unchanged. At the three higher dose levels, pharmacokinetics of the free
      antibody showed a serum half-life of 4.4 days (range, 1.6 to 10.5). Levels
      greater than 10 micrograms/mL persisted in 6 of 9 patients for more than 14 days.
      No quantifiable immune responses to the infused antibody have been detected.
      CD20+ B cells were rapidly and specifically depleted in the peripheral blood at
      24 to 72 hours and remained depleted for at least 2 to 3 months in most patients.
      Two-week postinfusion tumor biopsies showed the chimeric antibody bound to tumor
      cells and a decrease in the percentage of B cells. Tumor regressions occurred in
      6 of 15 patients (2 partial and 4 minor responses). The results of this single
      dose trial have been used to design a multiple-dose phase I/II study.

PMID- 7522633
TI  - Global vascular expression of murine CD34, a sialomucin-like endothelial ligand
      for L-selectin.
AB  - Extravasation of leukocytes into organized lymphoid tissues and into sites of
      inflammation is critical to immune surveillance. Leukocyte migration to
      peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) and Peyer's patches
      (PP) depends on L-selectin, which recognizes carbohydrate-bearing, sialomucin
      like endothelial cell surface glycoproteins. Two of these ligands have been
      identified at the molecular level. One is the potentially soluble mucin, GlyCAM
      1, which is almost exclusively produced by high endothelial venules (HEV) of PLN
      and MLN. The second HEV ligand for L-selectin is the membrane-bound sialomucin
      CD34. Historically, this molecule has been successfully used to purify human
      pluripotent bone marrow stem cells, and limited data suggest that human CD34 is
      present on the vascular endothelium of several organs. Here we describe a
      comprehensive analysis of the vascular expression of CD34 in murine tissues using
      a highly specific antimurine CD34 polyclonal antibody. CD34 was detected on
      vessels in all organs examined and was expressed during pancreatic and skin
      inflammatory episodes. A subset of HEV-like vessels in the inflamed pancreas of
      nonobese diabetic (NOD) mice are positive for both CD34 and GlyCAM 1, and bind to
      an L-selectin/immunoglobulin G (IgG) chimeric probe. Finally, we found that CD34
      is present on vessels of deafferentiated PLN, despite the fact that these vessels
      are no longer able to interact with L-selectin or support lymphocyte binding in
      vitro or trafficking in vivo. Our data suggest that the regulation of
      posttranslational carbohydrate modifications of CD34 is critical in determining
      its capability to act as an L-selectin ligand. Based on its ubiquitous
      expression, we propose that an appropriately glycosylated form of vascular CD34
      may act as a ligand for L-selectin-mediated leukocyte trafficking to both
      lymphoid and nonlymphoid sites.

PMID- 7522631
TI  - Engraftment of human hematopoietic precursor cells with secondary transfer
      potential in SCID-hu mice.
AB  - Human fetal bone fragments implanted subcutaneously in immunodeficient (SCID)
      mice maintain active human hematopoiesis. In this study, we show that this human
      hematopoietic microenvironment supports the engraftment and differentiation of
      HLA-mismatched, CD34+ primitive hematopoietic progenitor cells isolated from
      fetal and adult human bone marrow (BM). The BM CD34+ cells were depleted of CD2,
      CD14, CD15, CD16, glycophorin A, and CD19 lineage-committed cells (CD34+Lin-).
      Donor cell engraftment was manifested by the presence of B (CD19+) and myeloid
      (CD33+) cells of donor HLA phenotype. Successful engraftment was observed as
      early as 4 weeks after fetal BM donor cell injection and sustained for at least
      12 weeks, with engraftment success rates of 100% (11/11 grafts) and 92% (11/12
      grafts) at 8 and 12 weeks, respectively. Mixed BM chimerism of donor and
      endogenous cells was consistently observed in SCID-hu bones successfully
      engrafted with HLA-mismatched CD34+Lin- donor cells. Preconditioning of the SCID
      hu bone with a single dose of sublethal (350 rad) whole body irradiation (WBI)
      immediately before cell injection enhanced the repopulation of the bone grafts
      with donor cells and, in some instances, resulted in complete repopulation. After
      WBI, as few as 500 fetal bone marrow CD34+Lin- cells injected in the human bone
      grafts resulted in donor-derived hematopoiesis. Donor progenitor cells recovered
      from the SCID-hu bone grafts 8 weeks postinjection had the capacity to repopulate
      secondary groups of HLA-disparate fetal human bones in SCID-hu mice with B and
      myeloid cells as well as CD34+ cells in some recipients. In addition, these cells
      repopulated fetal human thymus fragments in SCID mice with donor thymocytes
      including immature CD4+CD8+ and mature CD4+CD8- as well as CD4-CD8+ subsets.
      These results indicate that the fetal human bone implants of SCID-hu mice can
      support the maintenance of a cell population that has both multilineage potential
      and repopulating potential for periods of time as long as 16 weeks. The SCID-hu
      bone model consistently supported the engraftment of both fetal and adult
      CD34+Lin- cells without the administration of exogenous human cytokines to these
      animals. This model is currently being used to permit the isolation and
      characterization of candidate human hematopoietic stem cells (HSCs) and provide
      important information critical for human HSC therapy in humans.

PMID- 7522630
TI  - Mast cells cultured from the peripheral blood of normal donors and patients with
      mastocytosis originate from a CD34+/Fc epsilon RI- cell population.
AB  - Mast cells may be cultured from human peripheral blood in the presence of
      recombinant human stem cell factor (rhSCF). The characteristics of the cells in
      peripheral blood that give rise to mast cells are unknown. Because mast cell
      precursors in human marrow are CD34+, human peripheral blood mononuclear cells
      from patients with mastocytosis and normal controls were sorted on the basis of
      CD34 expression and the positive and negative cell populations were cultured in
      rhSCF, recombinant human interleukin-3 (rhIL-3), or both for 6 weeks. Cell
      cultures were examined every 2 weeks for total and mast cell number and cell
      differential using Wright Giemsa and acid toluidine blue stains and antibodies to
      mast cell tryptase and chymase, cell-associated histamine, and expression of
      CD34, c-kit, Fc epsilon RI, and Fc gamma RII using flow cytometric analysis. The
      ultrastructural anatomy of mast cells was examined by electron microscopy.
      Peripheral blood CD34+ cells cultured in rhSCF with or without rhIL-3 gave rise
      to cell cultures consisting of greater than 80% mast cells by 6 weeks. CD34+
      cells cultured in rhIL-3 alone did not give rise to mast cells, whereas rhIL-3
      plus rhSCF increased the final mast cell number eightfold when compared with
      cells cultured in rhSCF alone. Mast cells increased concomitantly with a decrease
      in large undifferentiated mononuclear cells. CD34- cells did not give rise to
      mast cells. Histamine content per cell at 6 weeks was approximately 5 pg.
      Electron microscopy of 4-week cultures showed immature mast cells containing
      predominantly tryptase-positive granules that were either homogeneous or
      contained lattice structures, partial scroll patterns, or central dense cores and
      mixtures of vesicles, fine granular material, and particles. The CD34+ population
      at day 0 expressed Kit (65%) and Fc gamma RII (95%), but not Fc epsilon RI, by
      fluorescence-activated cell sorter analysis. At 6 weeks, CD34+-derived mast cells
      exhibited Fc epsilon RI in addition to Kit and Fc gamma RII, and were negative
      for CD34 antigen. Patients with mastocytosis showed a higher number of mast cells
      per CD34+ cell cultured compared with normal controls. Thus, the mast cell
      precursor in human peripheral blood is CD34+/Fc epsilon RI- and gives rise to
      mast cells in the presence of rhSCF with or without rhIL-3, and the number of
      mast cells arising per CD34+ cell in culture is greater when the CD34+ cells are
      obtained from patients with mastocytosis compared with normal subjects.

PMID- 7522632
TI  - Tumor necrosis factor alpha (TNF alpha) downregulates c-kit proto-oncogene
      product expression in normal and acute myeloid leukemia CD34+ cells via p55 TNF
      alpha receptors.
AB  - Tumor necrosis factor alpha (TNF alpha), as a modulator of hematopoiesis,
      interacts with many growth factor receptors, such as interleukin-3, granulocyte
      macrophage colony-stimulating factor (CSF), and granulocyte-CSF receptors. Here,
      we studied the interactions between TNF alpha and the stem cell factor (SCF)
      receptor, c-kit, in normal CD34+ hematopoietic progenitors and their leukemic
      counterpart, ie, acute myeloid leukemic (AML) CD34+ cells coexpressing c-kit
      antigen. The results showed that (1) incubation of normal bone marrow mononuclear
      cells with 200 U/mL rhTNF alpha for 20 hours induced a diminution of 31.2% +/-
      5.2% of CD34+ cells coexpressing c-kit; (2) the same decrease was observed using
      purified CD34+ cells and, furthermore, their proliferative response to SCF was
      inhibited by 31.5% +/- 7.3% after exposure to TNF alpha; (3) similar experiments
      performed on CD34+ c-kit+ AML cells from 11 patients gave comparable results.
      Further analysis at the mRNA level indicated that TNF alpha decreased c-kit mRNA
      transcripts. Moreover, using monoclonal antibodies against the two types of TNF
      alpha receptors, p75 and p55, we showed that the downregulation of c-kit proto
      oncogene product by TNF alpha, on normal and leukemic CD34+ cells, was
      exclusively mediated by the TNF alpha p55 receptor. Therefore, we conclude that
      TNF alpha acts as a downregulator of the SCF receptor expression.

PMID- 7522635
TI  - Expression of recombinant transmembrane CD59 in paroxysmal nocturnal
      hemoglobinuria B cells confers resistance to human complement.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic disorder
      characterized by complement-mediated hemolytic anemia, pancytopenia, and venous
      thrombosis. These clinical manifestations arise from an underlying molecular
      defect of bone marrow stem cells. Specifically, somatic mutations in the
      phosphatidylinositol glycan class A gene result in the ability of blood cells to
      anchor complement-regulatory proteins (CD59 and DAF) to the cell surface via
      glycosyl phosphatidylinositol (GPI). In an attempt to circumvent the functional
      defect in PNH cells, a recombinant transmembrane form of CD59 (CD59-TM) was
      analyzed for the ability to regulate complement activity. Balb/3T3 stable
      transfectants expressing similar levels of either CD59-TM or native CD59 (CD59
      GPI) were equally protected against human complement-mediated membrane damage.
      Treatment of these cells with phosphatidylinositol-specific phospholipase C
      failed to release CD59-TM from the cell surface. Retroviral transduction of GPI
      anchoring deficient mouse L cells with CD59-TM resulted in surface expression of
      the protein and rendered these cells resistant to human complement-mediated
      membrane damage. Conversely, L cells transduced with CD59-GPI failed to express
      this protein on the cell surface. A GPI-anchoring deficient complement-sensitive
      B-cell line derived from a PNH patient was successfully transduced with CD59-TM,
      resulting in surface expression of the protein. The PNH B cells expressing CD59
      TM were protected against classical complement-mediated membrane damage by human
      serum. Taken together, these data establish that a functional recombinant
      transmembrane form of CD59 can be expressed on the surface of GPI-anchoring
      deficient PNH cells and suggest that retroviral gene therapy with this molecule
      could provide a treatment for PNH patients.

PMID- 7522634
TI  - Expression of CD28 and CD40 in human myeloma cells: a comparative study with
      normal plasma cells.
AB  - CD28 and CD40 are important activation pathways for T and B lymphocytes,
      respectively. The aim of this study was to determine the phenotype of plasma
      cells (PCs) and the expression of these two molecules, CD28 and CD40. Therefore,
      we have compared their expression on normal PCs from bone marrows and tonsils
      with that of freshly explanted malignant PCs from 31 patients with multiple
      myeloma (MM) and those from 12 human myeloma cell lines. For this purpose, we
      first described a new approach to identify plasma cells in bone marrow using two
      color immunofluorescence analysis with anti-CD38 and B-B4 antibodies. B-B4
      specifically recognizes all PC; all B-B4 cells are located within the CD38 bright
      fraction and vice versa. CD19 and CD56 expression, which was previously shown to
      discriminate normal from malignant PCs, was also evaluated. In the current
      report, we show that normal PCs express CD19, CD40, and CD56 (weakly as a subset)
      and lack CD28. Regardless of whether they express CD19, CD56 is clearly
      upregulated during the medullary chronic and accelerated phases of MM, but is
      absent in patients with extramedullary involvement. Although the level of CD40
      expression is variable, only patients in accelerated phases expressed high CD40
      levels. Finally, whereas CD28 was negative in chronic phase (as in normal PCs),
      it was expressed in 63% of the patients in accelerated phases and 100% of cell
      lines. Our data strongly suggest that both disease activity and medullary homing
      (or not) are correlated with the expression of CD19, CD40, CD28, and CD56 on
      human myeloma cells.

PMID- 7522636
TI  - Properties of transcription factors regulating interleukin-2 gene transcription
      through the NFAT binding site in untreated or drug-treated naive and memory T
      helper cells.
AB  - Combining in vitro DNA binding studies and functional transcription assays in the
      Xenopus oocyte, we have tested the presence and functional state of transcription
      factors controlling the interleukin-2 (IL-2) promoter through the NFAT binding
      site. In naive T-helper cells, the IL-2 gene is repressed by a silencer. After
      first mitogenic stimulation, this silencer becomes undetectable while an
      activator is newly synthesized. In resting memory cells, the activator has low
      DNA-binding affinity and is located in the cytoplasm. However, no silencer is
      formed. Upon renewed cellular activation, this pre-existing activator is again
      targeted to the nucleus and regains function in promoting transcription.
      Cyclosporin A and FK506 act on two distinct levels of the IL-2 control mechanism.
      They prevent nuclear transport and reactivation of the performed activator in
      memory cells and, in naive cells, they render the silencer resistant to
      displacement by the activator. DNA-binding of silencer and activator from T
      helper, and NFAT-1 from Jurkat cells, requires the same three G residues, but
      cross-linking analyses show differences in their constituent subunits. Supershift
      experiments show that the activator contains fra-2 and junD, whereas the silencer
      reacts with none of the antibodies tested.

PMID- 7522637
TI  - Cross-linking of CD4 molecules upregulates Fas antigen expression in lymphocytes
      by inducing interferon-gamma and tumor necrosis factor-alpha secretion.
AB  - We have recently shown that, in unfractioned peripheral blood mononuclear cells
      (PBMCs), the cross-linking of CD4 molecules (CD4XL) is sufficient to induce T
      cell apoptosis. However, the underlying mechanism for the CD4XL-mediated T-cell
      apoptosis is largely unknown. Several recent studies have shown that Fas antigen
      (Ag), a cell-surface molecule, mediates apoptosis-triggering signals. We show
      here that cross-linking of CD4 molecules, induced either by anti-CD4 monoclonal
      antibody (MoAb) Leu3a or by human immunodeficiency virus-1 (HIV-1) envelope
      protein gp160, upregulates Fas Ag expression as well as Fas mRNA in normal
      lymphocytes. Addition of the tyrosine protein kinase inhibitor genistein or of
      the immunosuppressive agent cyclosporin A abrogated these effects. The
      upregulation of Fas Ag closely correlated with apoptotic cell death, as
      determined by flow cytometry. In addition, CD4XL resulted in the induction of
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the
      absence of interleukin-2 (IL-2) and IL-4 secretion in PBMCs. Both INF-gamma and
      TNF-alpha were found to contribute to Fas Ag upregulation and both anti-IFN-gamma
      and anti-TNF-alpha antibodies blocked CD4XL-induced Fas Ag upregulation and
      lymphocyte apoptosis. These findings strongly suggest that aberrant cytokine
      secretion induced by CD4XL and consequent upregulation of Fas Ag expression might
      play a critical role in triggering peripheral T-cell apoptosis and thereby
      contribute to HIV disease pathogenesis.

PMID- 7522638
TI  - Human T-cell leukemia virus type I tax/rex DNA and RNA in cutaneous T-cell
      lymphoma.
AB  - Peripheral blood mononuclear cells (PBMCs) and T-cell lines from patients with
      Sezary syndrome (SS) and skin lesions from patients with mycosis fungoides (MF)
      were examined by polymerase chain reaction (PCR) for DNA sequences homologous to
      the human retroviruses human T-lymphotropic virus (HTLV)-I and -II. Results
      obtained using primers and probes from the tax/rex region of HTLV-I indicate that
      72% (18/25) of SS patients PBMCs, 80% (20/25) of T-cell lines established from SS
      PBMC, and 30% (3/10) of skin lesions from MF patients were positive for HTLV-I
      tax/rex region DNA. Sequence analysis of the 127-bp fragment amplified by the
      tax/rex primers from 4 of these individuals was found to be identical to that in
      prototypic HTLV-I. Negative results were obtained using primers and probes from
      the HTLV-I gag region and the HTLV-II gag and tax regions. No PCR products were
      obtained using all primers and probes using DNA from 9 healthy blood donors and
      10 cord bloods. Expression of HTLV-I tax/rex mRNA was found in 4 of 8 Sezary
      patients, as determined by RNA-PCR, indicating that this viral region is being
      transcribed in vivo. Exposure to Tax/Rex protein in SS-patients is supported by
      the fact that serum antibodies against p27rex and p40tax was observed in 43% and
      29% of these SS patients, respectively. Although the causal relationship between
      the HTLV-I tax/rex region and cutaneous T-cell lymphoma (CTCL) remains unclear,
      these findings support the presence of a truncated HTLV-I retrovirus in CTCL
      patients.

PMID- 7522639
TI  - Identification and culture of Kaposi's sarcoma-like spindle cells from the
      peripheral blood of human immunodeficiency virus-1-infected individuals and
      normal controls.
AB  - We examined 26 patients with human immunodeficiency virus-1 (HIV-1)-associated
      Kaposi's sarcoma (KS), and 76 HIV-1-infected (HIV-1+) people without KS or
      uninfected (HIV-1-) controls for the presence of circulating KS-like spindle
      cells. Adherent cells that had spindle morphology and several characteristics of
      spindle cells of KS lesions (KS cells) were identified in the peripheral blood
      mononuclear cell fraction only after culture in the presence of conditioned
      medium (CM) from activated lymphocytes. The peripheral blood-derived spindle
      cells (PBsc) expressed a variety of endothelial cell markers, such as Ulex
      europaeus I lectin, EN4, EN2/3, EN7/44, CD13, CD34, CD36, CD54, ELAM-1, and HLA
      DR. However, they were negative for CD2, CD19, PaIE, and factor VIII-related
      antigen. The PBsc produced angiogenic factors as evidenced by the ability of CM
      from these cells to promote growth of normal vascular endothelial cells. In
      addition, subcutaneously injected PBsc stimulated angiogenesis in vivo in athymic
      nude mice. We determined that the number of PBsc grown from the peripheral blood
      of HIV-1+ patients with KS or at high risk to develop KS were increased by 78
      fold (P = .0001) and 18-fold (P = .005), respectively, when compared with HIV-1-
      controls. The number of spindle cells cultured from the HIV-1+ patients at low
      risk for developing KS, eg, HIV-1+ injection drug users, showed no statistical
      increase when compared with HIV-1- controls. The presence of increased PBsc with
      characteristics of KS cells in HIV-1+ KS patients or patients at high risk for
      developing KS gives insights into the origin of KS cells and may explain the
      multifocal nature of the disease. In addition, this may be useful in predicting
      the risk of KS development.

PMID- 7522640
TI  - E-selectin mediates leukocyte rolling in interleukin-1-treated rabbit mesentery
      venules.
AB  - The selectins are lectin-like cell surface glycoproteins that have been
      implicated in playing a crucial role in the initiation of leukocyte adhesion to
      endothelial cells (ECs) during inflammation. Binding of selectins under
      conditions of flow mediates leukocyte rolling, which in vivo is almost
      exclusively observed in venular microvessels. We have shown in previous
      experiments that intraperitoneal treatment of rabbits with interleukin-1 beta (IL
      1) increases leukocyte rolling in exteriorized mesenteries. In the present study,
      we used immunohistochemistry of mesenteries and found that IL-1 induced a marked
      E-selectin immunoreactivity, preferentially in venules. We therefore hypothesized
      that the increased rolling in response to IL-1 may be related to the induction of
      E-selectin on venular ECs. Intravital microscopy was used to investigate
      interactions between leukocytes and ECs after intraperitoneal application of IL
      1. The rabbit E-selectin monoclonal antibody (MoAb) 9H9 significantly reduced
      rolling of leukocytes by approximately 40%. Vehicle alone, class-matched control
      MoAb or the nonblocking anti-E-selectin MoAb 14G2 had no effect on rolling. These
      results indicate that leukocytes roll on inflamed venular ECs partly through
      interactions with E-selectin. Furthermore, we propose that the restricted E
      selectin immunoreactivity by venular ECs contributes to the remarkable difference
      seen between arterioles and venules in exhibiting leukocyte rolling in vivo.

PMID- 7522641
TI  - Polymorphonuclear neutrophils from human immunodeficiency virus-infected patients
      show enhanced activation, diminished fMLP-induced L-selectin shedding, and an
      impaired oxidative burst after cytokine priming.
AB  - Impaired polymorphonuclear neutrophil (PMN) function may contribute to the onset
      of certain life-threatening bacterial and fungal infections in human
      immunodeficiency virus (HIV)-infected patients. Published data on PMN functional
      activity in HIV infection are controversial, possibly because most studies have
      involved PMNs isolated from their blood environment by means of various
      procedures that may differently affect surface receptor expression and thereby
      alter cellular responses. We therefore used flow cytometry to study the
      expression of adhesion molecules at the PMN surface, actin polymerization, and
      the oxidative burst of whole-blood polymorphonuclear neutrophils in 42 HIV
      infected patients at different stages of the disease. These PMNs were activated
      in vivo, as demonstrated by increased expression of the adhesion molecule
      CD11b/CD18, reduced L-selectin antigen expression, increased actin
      polymerization, and increased H2O2 production. The alterations were present in
      asymptomatic patients with CD4+ cell counts greater than 500/microL and did not
      increase with the progression of the disease. Stimulation by bacterial N-formyl
      peptides showed dysregulation of L-selectin shedding and decreased H2O2
      production after ex vivo priming with tumor necrosis factor alpha or interleukin
      8 (IL-8). These latter impairments, which correlated with the decrease in CD4+
      lymphocyte numbers and with IL-8 and IL-6 plasma levels, could contribute to the
      increased susceptibility of HIV-infected patients to bacterial infections.

PMID- 7522642
TI  - Apoptosis and macrophage-mediated deletion of precursor B cells in the bone
      marrow of E mu-myc transgenic mice.
AB  - Transgenic mice expressing the c-myc proto-oncogene under the control of the Ig
      heavy chain enhancer (E mu-myc) all eventually develop clonal pre-B- or B-cell
      tumors. The preneoplastic period is characterized by increased polyclonal
      proliferation of pro-B and pre-B cells in the bone marrow (BM) associated with a
      reduced number of B cells, suggesting a high degree of B-cell loss. To examine
      the mechanisms of this cell loss, we have identified B220+ B-lineage cells within
      the BM of pretumorous E mu-myc transgenic mice by in vivo radiolabeling and
      electron microscope radioautography. Large mitotic B220(+)-labeled cells form
      prominent clusters in the extravascular compartment of the BM. Some B220+ small
      lymphocytes, as well as large lymphoid cells, enter BM sinusoids. However, in
      addition, large numbers of B220+ cells exhibit nuclear chromatin condensation,
      fragmentation, and other morphologic features characteristic of apoptotic cell
      death. Propidium iodide staining and flow cytometry of BM cells from pretumorous
      E mu-myc transgenic mice, as well as agarose gel electrophoresis of DNA, confirm
      extensive apoptosis. Many B220+ apoptotic cells are closely associated with the
      extensive processes of prominent macrophages that contain numerous B220+
      apoptotic bodies and complex lysosomal systems. These results suggest that the
      constitutive expression of c-myc oncogene in BM B-lineage cells, which increases
      the proliferation of precursor B cells, also leads to increased apoptotic cell
      death and rapid elimination by resident macrophages. Further mutations may be
      needed to block these protective mechanisms and permit surviving c-myc
      dysregulated cells to leave the BM and to initiate tumorigenesis.

PMID- 7522643
TI  - Characterization of CD34+ peripheral blood cells from healthy adults mobilized by
      recombinant human granulocyte colony-stimulating factor.
AB  - Primed peripheral blood hematopoietic stem cells (PBSC) generate and sustain
      lymphohematopoiesis in myeloablated animals, and recent reports indicate that
      allogeneic transplantation using PBSC grafts may be feasible in humans. A major
      concern with the use of PBSC transplants is that permanent engraftment may be
      limited because of lack of sufficient numbers of primitive progenitor cells in
      the graft. In the present study, in vitro colony formation and immunophenotype of
      CD34+ cells in PB of healthy adults during short-term granulocyte colony
      stimulating factor (G-CSF) administration were compared with that of CD34+ cells
      in normal bone marrow (BM). The number of CD34+ cells mobilized to PB peaked at
      day 4 or 5 of G-CSF administration. The phenotypic profile of CD34+ PB cells
      showed a substantial increase in the percentage of CD34+CD13+ and CD34+CD33+
      cells (myeloid progenitors) and a corresponding decrease in the percentage of
      CD34+CD10+ and CD34+CD19+ cells (B lymphoid progenitors) compared with CD34+ BM
      cells. The other subsets studied, including CD34+CD38- and CD34+HLA-DR- cells,
      were present in both compartments in similar proportions. Furthermore, primed
      CD34+ PB cells were enriched for colony-forming cells (CFC) and displayed an
      increased clonogenicity when compared with their counterparts in BM. A comparison
      between a postulated PBSC graft and an average BM graft is presented, showing
      that such PBSC grafts will be enriched for CD34+ cells as a whole, CD34+CD33+
      cells, and colony-forming cells (CFC), factors which have been shown to correlate
      to acceleration of hematologic reconstitution and reduction in requirements for
      supportive care in autografting. Hence, we predict that allogeneic
      transplantation using G-CSF-primed PBSC grafts will result in a more rapid
      hematologic reconstitution after myeloablative conditioning than BM grafting. The
      question of whether PBSC allografting will result in permanent engraftment and
      clinical benefits as observed in autografting has to be determined in prospective
      clinical studies.

PMID- 7522644
TI  - Prevention of graft-versus-host disease by peptides binding to class II major
      histocompatibility complex molecules.
AB  - Graft-versus-host disease across minor histocompatibility barriers was induced in
      two different models by transplanting allogeneic bone marrow and spleen cells
      into irradiated H-2-compatible recipient mice. In this report, we show that
      administration of peptides with high binding affinity for the respective class II
      major histocompatibility complex molecules after transplantation is capable of
      preventing the development of graft-versus-host disease in two different murine
      models. The peptides used were myelin basic protein residues 1 through 11 with
      alanine at position 4 (Ac 1-11[4A]) for I-Au (A alpha uA beta u), and the
      antigenic core sequence 323 through 339 of ovalbumin with lysine and methionine
      extension (KM core) for I-As (A alpha sA beta s). In both systems, the mechanism
      of prevention was found to be major histocompatibility complex-associated,
      because nonbinding control peptides did not have any effect. Engraftment of
      allogeneic bone marrow cells was shown by polymerase chain reaction analysis of
      DNA polymorphisms in a microsatellite region within the murine interleukin-5
      gene.

PMID- 7522645
TI  - Myeloid/natural killer cell acute leukemia: a previously unrecognized form of
      acute leukemia potentially misdiagnosed as FAB-M3 acute myeloid leukemia.

PMID- 7522646
TI  - Management of peritoneal effusions with intracavitary mitoxantrone or bleomycin.
AB  - Peritoneal effusion is a common complication in disseminated cancer.
      Intracavitary instillation of various agents has achieved control rates of 30-60%
      with no rational preference for one agent or another. However, serious side
      effects have also been observed and deaths due, for instance, to bleomycin have
      been reported. Mitoxantrone has recently been tested to treat effusions, and
      preliminary results suggest the high efficacy of this drug in the treatment of
      peritoneal, pericardial and pleural effusions. Nevertheless, some results have
      been conflicting. In the present study, 41 patients with peritoneal effusions
      were treated with intracavitary bleomycin or intracavitary mitoxantrone. The
      median duration of control of effusion was 5 months (range 1 week to 14 months)
      with mitoxantrone and 4 months (range 1 week to 12 months) with bleomycin. We
      conclude that, taking into account their limitations, both agents can be used
      successfully in the treatment of peritoneal effusions.

PMID- 7522647
TI  - Curative effects on rat sarcomas obtained after a treatment combining two
      monoclonal antibodies.
AB  - The effects of a treatment involving two monoclonal antibodies (Ab) were
      evaluated on benzo(a)pyrene [B(a)P]-induced malignant sarcomas in Sprague-Dawley
      female rats. These Ab were, respectively, an anti-anti-conjugated B(a)P AB, an
      internal image of conjugated B(a)P, called AIB1, and an anti-conjugated L-DOPA
      Ab. They were biweekly injected into animals with small clinically palpable
      tumors. Anti-'phosphatidylinositol-like' autoantibody (autoAb) levels which were
      significantly higher in B(a)P-treated rat sera were decreased after Ab treatment.
      Tumor growth was slowed down compared with that of controls and animal survival
      was increased. This treatment was more efficient than that involving AIB1 alone.
      The anti-conjugated L-DOPA Ab may play a role in neovascularization, which is
      known to be critical for tumor growth.

PMID- 7522648
TI  - Comparison between transforming growth factor alpha and epidermal growth factor
      in the protection of rat gastric mucosa against drug-induced injury.
AB  - This study was designed to compare the protective effect of recombinant human TGF
      alpha or EGF against drug-induced damage to the rat gastric mucosa. Parenteral
      administration of TGF alpha and EGF prevented 100% ethanol-induced mucosal injury
      to a similar extent. Furthermore, both peptides, in non-antisecretory doses,
      significantly decreased the gastric mucosal damage brought about by acidified
      aspirin. TGF alpha and EGF did not afford significant protection of the gastric
      mucosa when administered orogastrically. We also evaluated the effect of TGF
      alpha and EGF on insoluble (adherent) gastric mucin and found that both compounds
      dose-dependently stimulated adherent mucin in a time frame consistent with their
      protective effect. In conclusion, TGF alpha and EGF are equally effective in
      preventing drug-induced injury to the rat gastric mucosa.

PMID- 7522649
TI  - Treatment of hepatocellular carcinoma.

PMID- 7522650
TI  - Calling it quits: stopping futile treatment and caring for patients.

PMID- 7522651
TI  - Pattern formation in chick feather development: distribution of beta 1-integrin
      in normal and scaleless embryos.
AB  - We have examined the immunolocalization of beta 1-integrin during feather
      development in the spino-lumbar tract of the backskin from normal and scaleless
      chick embryos. beta 1-integrin appears during early feather development in three
      distinct phases which correspond to important developmental events. The first
      phase (5-5 1/2 days of incubation; Hamburger and Hamilton [H.H.] stage 27)
      represents the period prior to the formation of dermis. During this phase, beta 1
      integrin antiserum labels mesenchymal cells located in the central region of the
      spino-lumbar tract where the initiation site for feather development is located.
      The second phase (5 1/2-7 1/2 days of incubation; H.H. stages 28-32) corresponds
      to the period during which dermis is formed. The cells that make up the dermis
      are readily distinguished by their lack of beta 1-integrin immunostaining. The
      third phase (7 1/2-10 days of incubation; H.H. stages 33-36) begins with the
      sudden appearance of beta 1-integrin in the central and lateral regions of the
      dermis. The pattern of beta 1-integrin immunostaining in scaleless backskin
      becomes different from that of normal backskin during this phase. In normal
      backskin the dermal condensations of feather germs are not labeled with the beta
      1-integrin antiserum. This produces a heterogeneous immunostaining pattern very
      similar to the pattern seen for Type I collagen (Mauger et al. [1982] Dev. Biol.
      94:93-105). In contrast, homogeneous immunostaining is observed in the dermis of
      scaleless backskin. The initial time of appearance, manner of appearance, and
      pattern of integrin expression in the third phase suggest that beta 1-integrin
      may be involved in the stabilization of the feather pattern. We also observed the
      appearance of beta 1-integrin on the epidermal basal cells during the time of
      feather follicle formation. The beta 1-integrin antiserum reacts strongly with
      the baso-lateral surfaces of normal basal cells, yet the basal surfaces of the
      scaleless basal cells are unstained. This lack of immunostaining along the basal
      surfaces of the scaleless basal cells may relate to the abnormal adhesion between
      the epidermis and dermis in scaleless backskin.

PMID- 7522652
TI  - Effect of in ovo retinoic acid exposure on forebrain neural crest: in vitro
      analysis reveals up-regulation of N-CAM and loss of mesenchymal phenotype.
AB  - In a prior study of in ovo exogenous retinoic acid (RA) exposure, we observed a
      prolonged expression of cell surface N-CAM in cranial neural crest (NC) cells
      exhibiting migratory failure. In the present studies, we employed an experimental
      strategy in which embryos were first exposed to exogenous RA in ovo and incubated
      for 45-60 hr; this was followed by extirpation and in vitro culturing of these
      same RA-exposed cranial neural tubes. NC cell outgrowth from the explant was
      assayed, as was the immunohistochemical localization of HNK-1 and N-CAM antigens.
      In RA-exposed explants, the size of the NC cell outgrowths were comparable to
      controls. However, almost all NC cells lost their mesenchymal phenotype and were
      arranged in an "epithelioid" pattern of tightly packed polygonal cells that
      expressed N-CAM at adjacent cell boundaries. By contrast, control NC cells were
      flattened and multipolar in shape and expressed HNK-1, rarely co-expressing N
      CAM. These observations indicate that RA modulates NC cell N-CAM expression and
      microanatomical phenotype, a finding consistent with prior in ovo studies of RA
      exposure. Several possible explanations are considered.

PMID- 7522654
TI  - Endocytosis of three serum proteins of a multigene family and of arachidonic acid
      in human lectin-stimulated T lymphocytes.
AB  - Alpha-fetoprotein (AFP), serum albumin (SA), and vitamin D binding protein (DBP)
      are members of a multigene family of proteins showing high structural homology.
      AFP and SA exhibit a reciprocal relation during development and carry mostly
      fatty acids, while DBP carries vitamin D and its metabolites in the plasma.
      Covalent conjugates of these proteins with horseradish peroxidase (HRP) were used
      to follow by cytochemistry, at the electron microscope level, the protein uptake
      and intracellular pathways in peripheral blood human lymphocytes stimulated to
      blast formation by phytohemagglutinin (PHA). Transferrin (Tf), an iron-binding
      plasma protein, was used as a control. Combined with the results of competition
      and saturability experiments reported elsewhere, the ultrastructural observations
      are in favour of a specific endocytosis of the four proteins through cell surface
      receptors. Tf and AFP enter the cells via small vesicles and endosomes and move
      to multivesicular bodies (MVBs) and tubular vesicular elements located in the
      Golgi-centrosphere region to be finally recycled back into the medium. A
      noncovalent conjugate of AFP-HRP with 3H arachidonic acid [3H-(20:4)] is strongly
      internalized at 37 degrees C in PHA-stimulated lymphocytes; the autoradiographic
      labelling, localized in cellular membranes and mostly in lipid droplets, was only
      occasionally associated with organelles where the presence of AFP-HRP was
      cytochemically detected. SA, which competes with AFP for a common binding site on
      the surface of activated T cells, is endocytosed through small vesicles,
      endosomes, and MVBs before being released in a degraded form from the cells, in
      agreement with the localization of SA-HRP in lysosome-like organelles. DBP-HRP is
      poorly internalized through noncoated vesicles, endosomes, and MVBs and is
      finally routed to lysosomes. The physiological role of AFP and SA would be to
      mediate the transfer of fatty acids into cells, while that of DBP would be to
      facilitate the intracellular delivery of vitamin D.

PMID- 7522656
TI  - Adhesive properties of osteopontin: regulation by a naturally occurring thrombin
      cleavage in close proximity to the GRGDS cell-binding domain.
AB  - Osteopontin (OPN) is a secreted adhesive glycoprotein with a functional glycine
      arginine-glycine-aspartate-serine (GRGDS) cell-binding domain. An interesting
      feature of OPN structure is the presence of a thrombin-cleavage site in close
      proximity to the GRGDS region. Cleavage of OPN by thrombin is likely to be of
      physiological importance, because cleavage of blood plasma OPN occurs naturally
      after activation of the blood coagulation pathway. To investigate functional
      consequences of OPN cleavage by thrombin, cell attachment and spreading assays
      were performed with uncleaved and cleaved forms of OPN. For all cell lines
      examined, thrombin-cleaved OPN promoted markedly greater cell attachment and
      spreading than uncleaved OPN. Cell attachment and spreading on thrombin-cleaved
      OPN was inhibited both by the soluble GRGDS peptides and an OPN-specific antibody
      raised to the GRGDS domain of OPN, thus implicating the GRGDS region in mediating
      the increased cell attachment and spreading observed on thrombin-cleaved OPN.
      Because the GRGDS sequence in OPN is only six residues from the thrombin-cleavage
      site, the data suggest that possibility that thrombin cleavage allows greater
      accessibility of the GRGDS domain to cell surface receptors. To investigate
      receptors that recognize uncleaved and thrombin-cleaved OPN, affinity
      chromatography was performed on placental extracts; the cell surface integrin
      alpha v beta 3 bound to columns constructed either with native or thrombin
      cleaved OPN and was selectively eluted from each with soluble GRGDS peptide and
      EDTA. Moreover, adhesion assays performed in the presence of alpha v beta 3
      blocking monoclonal antibody LM609 identified alpha v beta 3 as a major
      functional receptor for thrombin-cleaved OPN. Several lines of evidence suggest
      that cleavage of OPN by thrombin occurs in vivo, such as in tumors and at sites
      of tissue injury, and adhesion assay data presented here indicate that such
      cleavage is important in the regulation of OPN function.

PMID- 7522655
TI  - Localization of an alpha 1,2 galactosyltransferase activity to the Golgi
      apparatus of Schizosaccharomyces pombe.
AB  - We have cloned a gene encoding an alpha 1,2 galactosyltransferase activity from
      Schizosaccharomyces pombe. The open reading frame of the gene (gma12 for
      galactomannan, alpha 1,2), combined with the previous protein purification
      (Chappell and Warren, 1989), predicts an O-linked glycoprotein with type II
      transmembrane topology. By homologous gene disruption, we have demonstrated that
      the gma12 gene product (gma12p) is nonessential. The deletion strain (gma12
      D10::ura4) has a significantly reduced level of galactosyltransferase activity
      relative to the parental strain, but both in situ lectin binding and in vitro
      biochemical assays demonstrate the presence of further galactosyltransferase
      activity in addition to gma12p. Although gma12p is not the only
      galactosyltransferase in S. pombe, it produces a unique carbohydrate structure on
      the surface of the yeast cells. We have generated a polyclonal antiserum against
      this carbohydrate epitope and shown that gma12p is capable of synthesizing the
      epitope both in vitro and in vivo. Electron microscopic localization of the
      gma12+ specific epitope in gma12+ cells revealed that gma12p synthesizes the
      carbohydrate structure in the Golgi apparatus, and subsequent intracellular
      transport distributes the epitope to later stages of the secretory pathway. The
      immunolocalization studies confirm the presence of one or more
      galactosyltransferase activities in the Golgi apparatus in fission yeast.

PMID- 7522653
TI  - Backscatter electron imaging of double immunogold labeled erythrocytes using two
      primary monoclonal IgM antibodies.
AB  - The majority of mouse monoclonal antibodies reacting with blood group epitopes on
      erythrocytes are of the IgM class, have equal light chain type, and are available
      as culture supernatants only. To study the interrelationship of the blood group
      antigens, a method is presented which allows double labeling applying two
      unconjugated monoclonal antibodies of the same class and species. The method
      comprises two indirect, sequential labelings using mouse IgM anti-A and anti-H as
      primary antibodies and two goat anti-mouse IgM conjugated to 30 and 20 nm
      colloidal gold particles as secondary antibodies. After labeling for the first
      antigen, free binding sites on the primary antibody are blocked by incubation
      with an unconjugated goat anti-mouse antibody. The free anti-species on the
      secondary antibody, conjugated to 30 nm gold particles, are inactivated by silver
      enhancement. The silver enhancement also enlarges the gold particle for optimal
      discrimination between the two particle sizes, which are chosen accordingly.
      Semiquantitations of double labeled cells from subgroup A2 and A3 were found to
      be in good agreement with the counts of the corresponding single labelings as
      well as between experiments, irrespective of which of the two antibodies was
      applied in the first labeling sequence. The results were in accordance with a
      reciprocal but nonlinear relationship between the A and H antigens and suggest
      different affinities of the two antibodies for the epitopes in the subgroups
      investigated, indicating different biochemistry of the antigen determinants.

PMID- 7522662
TI  - Clinical utility of acridine orange stained buffy coat smears.

PMID- 7522661
TI  - Mass losses and changes in concentration of chlorpyrifos and cis- and trans
      permethrin applied to the surface of a stream.

PMID- 7522659
TI  - Modulation of collagen synthesis and degradation by retinoids and cytokines in
      3T3 L1 preadipocytes.
AB  - We previously observed that a retinoid analog can protect against liver
      parenchymal damage and liver fibrosis, whereas it accelerates liver fibrosis
      which is not accompanied by any parenchymal damage. To elucidate these
      conflicting effects, we examined the effects of retinoid in 3T3 L1 preadipocytes
      as a model of liver stellate cells. Retinoids, including all-trans retinol, all
      trans and 9-cis retinoic acids, enhanced the cell growth and the expression of
      the type I procollagen gene as well as its peptide synthesis, while reducing
      collagenase activities. Although no retinoid enhanced the transforming growth
      factor (TGF)-beta 1 mRNA, retinoids may stimulate collagen production through
      activating TGF-beta, as was recently reported. These results help explain the
      observation in the liver fibrosis model with no parenchymal damage. In contrast,
      we also found that interferon (IFN) alpha beta and gamma inhibited cell growth
      and down-regulated markedly type I procollagen as well as TGF-beta 1 mRNA,
      suggesting that they suppress by acting directly on extracellular matrix
      producing cells.

PMID- 7522657
TI  - Histamine2-antagonists in allergic disorders.

PMID- 7522660
TI  - Two thoracolumbar spinal tumors causing pain and gait problems.

PMID- 7522658
TI  - Palliative high-dose octreotide in a case of severe AIDS-related diarrhea.

PMID- 7522664
TI  - Alamethicin: a peptide model for voltage gating and protein-membrane
      interactions.

PMID- 7522663
TI  - Actions of isoprenaline on amylase and total protein content of whole saliva in
      control, cystic fibrosis and cystic fibrosis heterozygote individuals.

PMID- 7522665
TI  - Annexin structure and membrane interactions: a molecular perspective.

PMID- 7522668
TI  - Voltage-dependent gating of ionic channels.

PMID- 7522666
TI  - Cyclic nucleotide-gated ion channels and sensory transduction in olfactory
      receptor neurons.

PMID- 7522670
TI  - [New biliary endoprostheses].

PMID- 7522667
TI  - Molecular dynamics simulations of the gramicidin channel.

PMID- 7522669
TI  - Effect of root conditioning on periodontal microvascular wound healing with and
      without guided tissue membrane: a pilot study.
AB  - The aim of this study was to determine (1) the influence of root conditioners,
      i.e., citric acid (CA) and tetracycline (TC), on the vascular response of closed
      periodontal wounds, and (2) the effect of implantation of nonresorbable membranes
      on the vascularization process. Thirty-two alveolar fenestrations were created in
      the maxillae of four healthy dogs. The depth of the fenestrations reached the
      periodontal ligament, cementum, and dentin. Topical application of CA, TC, or
      sterile water (SW) was done on the exposed dentin. Nonresorbable membranes were
      then implanted in half of the created defects between the mucoperiosteal flap and
      the alveolar bone. The vascular response at the experimental sites was determined
      by histological evaluation and cleared specimens following observation periods of
      3, 7, 14, and 21 days post-operatively. Results from this pilot study indicated
      that: (1) the coronal aspect of the periodontal ligament contributed the most to
      the initial vascularization of the defect; (2) there was no definitive advantage
      of the administration of CA or TC on the vascular response at 14 or 21 days; (3)
      no differences in vascular response were observed between treatment with or
      without the implantation of nonresorbable membranes; and (4) at 21 days, the
      vasculature in the defect area had not returned to its presurgical state.

PMID- 7522671
TI  - Evaluation of anti-HCV ELISA seropositivity in voluntary blood donors: a proposal
      for donor counseling strategies.
AB  - OBJECTIVE: To evaluate the anti-HCV (hepatitic C virus) reactivity for the
      development of an individual donor counseling strategy which would prevent
      unnecessary donor deferment without compromising the safety of blood products.
      DESIGN: All donors, who were repeatedly reactive in the Ortho HCV ELISA as well
      as the Abbott HCV EIA screening tests were selected for follow-up testing. At
      follow-up three screening tests (Ortho, Abbott, and UBI HCV EIA) and two
      confirmation tests (Riba 4 and PCR HCV RNA) were performed. During the counseling
      interview risk factors and medical history were recorded. SETTING: Blood bank
      Zuid-Limburg, Maastricht, the Netherlands; estimated donor population 17,500.
      PARTICIPANTS: A total of 54 donors could be completely evaluated. RESULTS: The
      participants could be divided into five different categories, requiring specific
      donor information and different blood bank policies. The donors in categories 1
      and 2 (n = 11) had false-positive reactions and were kept active. Category 3 and
      4 donors (n = 28) showed indeterminate results and were permanently or
      temporarily excluded. Finally, in category 5 donors (n = 15) a HCV infection
      could be diagnosed on the basis of either Riba-positive or PCR-positive results.
      CONCLUSIONS: An anti-HCV screening policy should include a careful evaluation and
      confirmation of antibody reactivity. A strategy is suggested which allows an
      individual donor counseling, prevents unnecessary donor deferment, and avoids
      unnecessary fear of seropositivity.

PMID- 7522672
TI  - Keratin diseases.
AB  - The recent discovery that epidermal fragility syndromes can be caused by
      mutations in the genes for keratin intermediate filaments has been a turning
      point for research into these structural proteins. Clustering of pathogenic
      mutations implies differential structural sensitivity along the keratin molecule,
      and implications for filament function require a new look at culture assay
      systems, plus a reassessment of structural defects in epithelial and other
      tissues.

PMID- 7522673
TI  - Cystic fibrosis gene therapy.
AB  - A variety of cystic fibrosis gene therapy approaches based on viral (adenovirus,
      retrovirus, and adeno-associated virus) and non-viral (liposomes and receptor
      mediated endocytosis) routes are currently being assessed for safety and
      efficacy. Of these, the trials involving liposomal and adenoviral vectors are the
      most advanced, as both have been shown to correct the cystic fibrosis Cl-
      conductance defect in vivo.

PMID- 7522674
TI  - Intracellular channels.
AB  - Intracellular channels are located on the membranes of intracellular organelles
      and are involved in ion transfer, within the cytosolic compartments, in response
      to internal stimuli. Recently, various types of inositol 1,4,5-trisphosphate- and
      ryanodine-sensitive Ca(2+)-release channels, mitochondrial voltage-dependent
      anion channels, and a vesicular Cl- channel have been molecularly cloned and
      characterized, and their functional roles in the central nervous system are
      beginning to be clarified.

PMID- 7522676
TI  - Glutamate receptor update.
AB  - The past year has seen significant advances in matching the actions of
      recombinant glutamate receptors with the actions of native receptors, and in
      mapping their distribution and regulation. The discovery of a novel RNA editing
      mechanism for AMPA receptors and a revised view of the transmembrane topology of
      the NMDA receptor subunit, NR1, are particularly noteworthy. Seven metabotropic
      glutamate receptor subtypes have been identified with several interesting
      expression patterns and transduction mechanisms; results from work on these
      subtypes has led to a provocative model of the ligand-binding site. Functional
      studies of metabotropic receptors have been enhanced by the development of the
      first subtype-specific antagonist.

PMID- 7522675
TI  - Structural basis of ion channel permeation and selectivity.
AB  - There has been rapid progress in understanding the structural basis of ion
      selectivity and permeation in both ligand- and voltage-gated channels.
      Recognition of similarities in overall architecture within a channel class has
      led to an increasing focus on the specific molecular determinants that endow a
      channel with its own distinctive character. It has been possible in some cases to
      identify individual amino acids essential for ion selectivity.

PMID- 7522677
TI  - ATP receptors.
AB  - ATP receptors continue to be found in an ever wider range of tissues in the brain
      and the periphery. Much of the recent research on these receptors focuses on
      features that would distinguish ATP-mediated excitatory synaptic transmission
      from that mediated through glutamate or acetylcholine receptors. These features
      include kinetics of the synaptic currents, voltage-independent calcium
      permeability of the underlying channels, interactions with adenosine, and various
      direct modulators of the ATP-gated ion channel.

PMID- 7522678
TI  - Mechanisms shaping glutamate-mediated excitatory postsynaptic currents in the
      CNS.
AB  - Excitatory postsynaptic currents in neurones of the central nervous system have a
      dual-component time course that results from the co-activation of AMPA/kainate
      type and NMDA-type glutamate receptors. New approaches in electrophysiology and
      molecular biology have provided a better understanding of the factors that
      determine the kinetics of excitatory postsynaptic currents. Recent studies
      suggest that the time course of neurotransmitter concentration in the synaptic
      cleft, the gating properties of the native channels, and the glutamate receptor
      subunit composition all appear to be important factors.

PMID- 7522680
TI  - Subtractive cDNA cloning as a tool to analyse secondary effects of a muscle
      disease. Characterization of affected genes in the myotonic ADR mouse.
AB  - In myotonic ADR mice that are homozygous for a defect in the muscular chloride
      channel gene adr/Clc-1, the hyperexcitability of fast muscles is associated with
      secondary changes in gene expression and fibre type composition. cDNA clones
      derived from a set of genes down regulated in fast muscles of the myotonic ADR
      mouse were isolated by a subtractive cloning procedure. A total of 1200 clones
      were analysed for high expression in fast muscle of wild type and low expression
      in mutant mouse. Differential transcript levels were verified by northern blot
      hybridizations. The identities of the corresponding transcripts were determined
      by sequencing as myosin heavy chain IIB, alpha-tropomyosin, troponin C, a Ca2+
      ATPase and parvalbumin mRNAs. Of these, mRNAs for parvalbumin and myosin heavy
      chain IIB were drastically downregulated in myotonic muscle (to < 10% of
      control). A full length cDNA clone for skeletal muscle alpha-tropomyosin was
      homologous to the mouse fibroblast tropomyosin isoform 2, except for the portion
      encoding the alpha-tropomyosin specific amino acids 258-284. A cDNA derived from
      the 1100 nucleotide parvalbumin transcript was cloned and the sequence for the as
      yet unknown 3' extended trailer, generated by alternative polyadenylation, was
      determined.

PMID- 7522679
TI  - Application of 1D and 2D NMR techniques to the structure elucidation of the O
      polysaccharide from Proteus mirabilis O:57.
AB  - The LPS O-polysaccharide (O-PS) produced by Proteus mirabilis serotype O:57 (ATCC
      49995) was shown by NMR spectroscopy and chemical analysis to be a high-molecular
      weight acidic branched polymer of pentasaccharide repeating units, composed of D
      glucose, D-galactose, 2-acetamido-2-deoxy-D-galactose and glycerophosphate
      residues (1:2:2:2:1). Application of one- and two-dimensional NMR methods allowed
      the complete assignment of notoriously crowded 1H and 13C spectra of the O-PS,
      leading to the determination of its structure. Several of the NMR techniques used
      were applied for the first time to the structure elucidation of polysaccharides.
      The resonances of galactose H5, H6 and H6' were identified by a 1D analog of 3D
      NOESY-TOCSY and 2D (1H,1H) triple-quantum experiments. The position and the
      nature of the phosphate group were determined from 2D 31P (omega 1)-half-filtered
      COSY and 2D 31P-relayed COSY spectra. 2D HMQC-TOCSY and 2D single-quantum proton
      carbon long-range correlation techniques were used to overcome the difficulties
      of severe overlap and higher order effects in the 1H NMR spectrum of the O-PS.
      The latter technique, together with 2D NOESY, enabled us to identify the
      substitution positions, the anomeric configurations and the sequence of the
      component glycose residues in the O-PS.

PMID- 7522681
TI  - Hyaline body myopathy.
AB  - Muscle biopsy from two unrelated patients, a male aged 40 and a female aged 3,
      with relatively non-progressive limb weakness since infancy, revealed numerous
      subsarcolemmal glassy, hyaline appearing bodies present in 20-30% of the fibres.
      Type 1 fibre predominance was present, and the hyaline bodies were exclusive to
      type 1 fibres. The hyaline bodies were negative with oxidative enzyme and
      periodic acid-Schiff stains. Electron microscopy showed the hyaline bodies to
      contain amorphous granular material of unknown composition. No membrane separated
      the hyaline bodies from the surrounding sarcoplasm. Hyaline body myopathy most
      likely represents a distinct congenital myopathy because of its childhoot-onset,
      non-progressive course, and distinct morphological features.

PMID- 7522682
TI  - The immunomodulatory effects of antithyroid drugs.

PMID- 7522685
TI  - Soluble P-selectin in the plasma of patients with connective tissue diseases.
AB  - We measured the soluble P-selectin (sP-selectin) in plasma of 54 patients with
      connective tissue diseases and 12 normal controls by a 2-step sandwich enzyme
      immunoassay. Our purpose was 2-fold: to determine (1) whether the level of sP
      selectin of such patients is higher than normal, and (2), if it is, whether it
      correlates with any of the laboratory data currently available. The mean levels
      in patients with systemic lupus erythematosus (SLE), mixed connective tissue
      disease (MCTD) and rheumatoid arthritis (RA) were 306, 1,048 and 844 ng/ml,
      respectively, compared with 220 ng/ml for controls. The mean levels in patients
      with SLE and nephropathy, MCTD and either nephropathy or thrombosis, and
      malignant RA were 351, 1,116 and 1,721 ng/ml, respectively. No correlation was
      found between the levels of sP-selectin and other laboratory data (WBC, CRP, ESR,
      antinuclear antibody, RF, aCL) except the number of platelets (y = 0.057, r =
      0.37). In the clinical course of patients with lupus nephritis and MCTD with
      nephropathy, sP-selectin became a sensitive parameter. Thus, the level of sP
      selectin is higher than normal in patients with connective tissue diseases,
      especially when complications exist, and it does not correlate with any of the
      laboratory data currently available except the number of platelets. Measurement
      of sP-selectin levels should be included in the laboratory tests of patients with
      connective tissue diseases, especially when complicated by nephropathy or
      thrombosis.

PMID- 7522686
TI  - Identification of the disease-related T cell epitope of ovalbumin and epitope
      targeted T cell inactivation in egg allergy.
AB  - An ovalbumin (OVA)-specific T cell line (TCL) was established from a patient with
      hen egg allergy. The TCL was CD4+, expressed alpha beta T cell receptor, and
      recognized OVA presented by HLA-DR10. Based on the response of the TCL to
      synthetic OVA peptides, it was found that the TCL recognized OVA 323-339, which
      is a major T cell epitope presented by murine I-Ad. The TCL secreted high levels
      of IL-5, but undetectable amounts of IL-2, interferon-gamma, and IL-4 when
      stimulated with OVA or the OVA 323-339 peptide. Since IL-5 is an important growth
      and chemotactic factor for eosinophils, it is possible that these OVA 323-339
      specific T cells can contribute to human egg allergy. To our knowledge, this is
      the first demonstration of food allergen-specific TCL establishment and
      identification of a T cell epitope possibly related to the allergic reaction to
      food antigens. An analog peptide of the OVA 323-339 which is known to strongly
      bind to I-Ad partially inhibited the response of the TCL to OVA 323-339 presented
      by HLA-DR10, raising the possibility of peptide-based immunotherapy of food
      allergy.

PMID- 7522687
TI  - Effects of long-acting beta 2-adrenoceptor agonists on mast cells of rat, guinea
      pig, and human.
AB  - The effects of two recently developed long-acting beta 2-adrenoceptor agonists,
      formoterol and salmeterol, on mast cells from different sources were compared
      with those of the prototype short-acting analogue, salbutamol. With the exception
      of high concentrations of salmeterol (> 10(-5) M), none of the tested beta 2
      adrenoceptor agonists inhibited the anti-IgE-induced histamine release from rat
      peritoneal mast cells. In contrast, all three compounds dose dependently
      inhibited the immunologically induced histamine release from isolated lung mast
      cells of guinea pig and human at concentrations < or = 10(-5) M.

PMID- 7522683
TI  - Long-term follow-up of thyroid scintigraphies after 131I therapy of solitary
      autonomous thyroid nodules.
AB  - The aim of the present study was to assess thyroid scintigraphies after 131I
      treatment of autonomous thyroid nodules with respect to evolution of the hot
      nodules as well as the extranodular tissue. A 99mTc pertechnetate scintigraphy
      was carried out 1-16 years (median 8 years) after 131I treatment of a solitary
      autonomous nodule in 66 patients remaining euthyroid. At the time of diagnosis, 9
      of the patients were euthyroid and 57 were hyperthyroid, of whom 27 received
      antithyroid drug therapy prior to 131I treatment. The scintigraphies were
      evaluated twice by 4 specialists (3 endocrinologists and 1 specialist in nuclear
      medicine). There was total agreement between the 4 observers in 50 and 52% in the
      first and second evaluation, respectively. The interobserver variation was
      evaluated by means of omega coefficients and omega ranged from 0.18 to 0.76
      indicating poor to substantial agreement. A solitary autonomous nodule with
      suppression of the extranodular thyroid tissue persisted in 50% of the patients,
      whereas a solitary cold nodule, homogeneous uptake or inhomogeneous uptake was
      found in 15, 22, and 13%, respectively. We conclude that although euthyroidism is
      achieved by radioiodine treatment, a hot nodule suppressing the 99mTc
      pertechnetate in the extranodular tissue is still found in 50% of the patients
      even when serum TSH has been normal for years. Antithyroid drug therapy prior to
      131I treatment was more frequent in this group of patients.

PMID- 7522684
TI  - Evidence that the immunosuppressive effects of antithyroid drugs are mediated
      through actions on the thyroid cell, modulating thyrocyte-immunocyte signaling: a
      review.
AB  - The mechanism of action of the immunosuppressive effects of antithyroid drugs has
      remained a matter of controversy, despite our earlier contention that such
      effects in vivo were indirect, i.e., it was our view that the drugs were acting
      on the thyroid cells, reducing their hormone production and other activities,
      with a consequent reduction in thyrocyte-immunocyte signaling. The reduction in
      the activation of CD4+ cells, the increased number and activation of CD8+ (and
      CD8+CDIIb+) cells, and the reduction of soluble interleukin-2 receptors, thought
      once to be direct effects of the medication, are now shown to be due to
      amelioration of the hyperthyroidism. Thus the reduction in thyroid hormone
      production induced by the drugs is central to these actions. In addition, the
      iodination of thyroglobulin is inhibited by these agents, which may affect
      antigen presentation by the thyrocyte. Furthermore, there is now evidence that
      the thionamides interfere with thyrocyte expression of Class I antigen,
      interleukin-1, interleukin-6, prostaglandin E2, and heat shock protein. The
      expression of thyrocyte Class II antigen is probably not inhibited by these
      drugs, although one group has shown that lectin-stimulated thyrocyte Class II
      expression is diminished by this treatment; this group postulated that this
      effect might be mediated by reduced interferon-gamma production by T lymphocytes,
      but in vitro experiments do not corroborate this proposal. In any event, the
      actions as described, of the antithyroid drugs on the thyroid cells, would
      certainly suffice to explain the diminution of thyroid antibodies (including
      thyroid stimulating antibody), the reduced immunological response, and the
      increased remission rate in Graves' disease, without the need to invoke a direct
      immunosuppressive effect.

PMID- 7522691
TI  - Mast cell recovery following chronic treatment with compound 48/80.
AB  - Histochemical and functional properties of mast cells (MC) in Brown Norway rats
      recovering from chronic treatment with the MC secretagogue compound 48/80 were
      examined. In the skin, treatment for 5 days with compound 48/80 resulted in a
      marked decrease in MC subpopulations defined by differential alcian blue/safranin
      staining. Both safranin-positive connective tissue MC and alcian blue staining MC
      were reduced in number. This was accompanied by significant decreases in skin
      histamine and rat MC serine protease I contents and a loss of specific IgE
      mediated passive cutaneous anaphylaxis (PCA) activity. The PCA reaction did not
      return to normal before 2 months after stopping treatment and only when the
      numbers of safranin-positive connective tissue MC and skin histamine content
      reached pretreatment levels. The subepidermal alcian blue staining MC not
      eliminated by the compound 48/80 treatment were formalin resistant (unlike alcian
      blue staining mucosal MC of the intestine) and apparently played no role in the
      PCA response. MC numbers, histamine levels, and rat MC serine protease I content
      of the tongue were similarly decreased by compound 48/80. In contrast, mucosal MC
      of the gut were unaffected by the secretagogue treatment.

PMID- 7522692
TI  - alpha-Fetoprotein levels of paired samples between the amniotic fluid and
      maternal serum from 16 to 18 weeks' gestation in Chinese women.
AB  - To assess the relationship between alpha-fetoprotein (AFP) concentrations of
      amniotic fluid and maternal serum from 16 to 18 weeks' gestation, 890 paired
      samples of maternal serum and amniotic fluid were collected from women with
      normal singleton pregnancies. The gestational age was determined by
      ultrasonographic dating before amniocentesis, and the AFP measurements were
      performed by a single reference laboratory. There was a significant rise in the
      maternal serum AFP (MSAFP) concentration from 16 to 18 weeks' gestation. Amniotic
      fluid AFP concentrations significantly declined from 16 to 18 weeks' gestation.
      This study failed to demonstrate any statistical relationship between the AFP
      concentration of maternal serum and amniotic fluid (r = 0.031). This finding
      indicates that amniotic fluid AFP levels cannot be predicted by MSAFP levels
      between 16 and 18 weeks' gestation. Simple diffusion may not be the only
      mechanism for the transfer of AFP through the fetal membrane to maternal
      circulation.

PMID- 7522688
TI  - Effects of B subunit of cholera toxin on histamine release from rat peritoneal
      mast cells.
AB  - We studied the effects of B subunit of cholera toxin (CTB) on secretagogue
      induced histamine release from rat peritoneal mast cells. CTB inhibited the
      release of histamine in response to compound 48/80, but not in response to
      mastoparan, substance P, concanavalin A or ionophore A23187. The results suggest
      that CTB can be used as a tool for studying the cellular events involved in
      histamine release from mast cells.

PMID- 7522690
TI  - Inhibition of stem cell factor dependent formation of human mast cells by
      interleukin-3 and interleukin-4.
AB  - In murines, interleukins (IL) 3, 4, 9, and 10, nerve growth factor, and stem cell
      factor induce or promote growth and differentiation of mast cells (MC). Increased
      stimulation and synergy was observed when combinations of cytokines were used. In
      man, no growth factor for human MCs had been identified until recently, when SCF
      was found to induce in vitro growth and differentiation of human MCs. In the
      present study, the effects of recombinant human IL-3 and IL-4 on SCF-dependent
      differentiation of human MCs from their circulating progenitor cells in long-term
      culture were analyzed. Surprisingly, both IL-3 and IL-4 were found to inhibit SCF
      dependent formation of human MCs (SCF, 100 ng/ml: 36.4 +/- 18.7 x 10(3)/ml; SCF +
      IL-3, 100 U/ml: 23.4 +/- 4.2 x 10(3)/ml; SCF + IL-4, 100 U/ml: 7.4 +/- 4.4 x
      10(3)/ml) and synthesis of MC tryptase (SCF, 100 ng/ml: 73.2 +/- 17.6 ng/ml; SCF
      + IL-3, 100 U/ml: 10.8 +/- 3.1 ng/ml [p < 0.01]; SCF + IL-4, 100 U/ml: 8.1 +/-
      1.5 ng/ml, [p = 0.02]). The inhibitory effects of these cytokines on SCF
      dependent formation of human MCs were associated with an increase in the number
      of macrophages (IL-3) or lymphocytes (IL-4) in the same cultures and may be due
      to competitive recruitment of cells from a pool of multilineage hematopoietic
      progenitor cells.

PMID- 7522689
TI  - Heparin mediates binding of S-protein/vitronectin to the envelope glycoprotein of
      the human immunodeficiency virus and CD4.
AB  - Using normal human serum and EDTA-plasma as the two sources of S-protein
      (vitronectin) in an enzyme-linked immunosorbent assay, we determined that heparin
      pretreatment of immobilized rgp120 or of immobilized CD4 caused the serum form of
      S-protein to deposit in a dose-dependent manner. Interestingly, the EDTA-plasma
      form of S-protein (native form) had little or no interaction with either of the
      heparin-treated surfaces. Several other sulfated polysaccharides such as dextran
      sulfate, pentosan polysulfate, heparan sulfate, and fucoidan, likewise mediated
      the deposition of the serum form S-protein on immobilized rgp120 and CD4. These
      findings may explain why certain glycosaminoglycans are effective against HIV
      infectivity in cell culture where the serum form of S-protein is present, yet
      ineffective in vivo where the native form of S-protein is predominant. The
      elevated glycosaminoglycan levels in gingival crevicular exudates, coupled with
      the effects of the serum form of S-protein and salivary-mediated neutralization
      mechanisms may explain the reduced rates of salivary HIV transmission.

PMID- 7522693
TI  - [Endogenic vasomotor function and smooth muscle insufficiency in the vascular
      microcirculation].
AB  - The paper outlines the previously unknown smooth muscle insufficiency in terms of
      its etiology, pathogenesis, diagnosis and treatment. It has been shown that drug
      administration leads to smooth muscle insufficiency which is eliminated by
      serotonin both in vitro and in vivo. The clinical manifestations of smooth muscle
      (SM) insufficiency are eliminated by serotonin, irrespective of whether it has
      been caused by the use of drugs or impaired smooth muscle innervation. The
      mechanism of vascular rhythmic oscillations in the microcirculatory bed, the so
      called endogenous vasomotility (EV) has been decoded. The mechanism of EV
      regulation is due to the fact that platelets constantly (continuously) adsorb
      serotonin from the enterochromaffin cells of the gastrointestinal tract and
      constantly (continuously) release it into the microcirculatory bed, thereby
      providing the continuum of entry of the stimulant to the SM fibers which are able
      to contract at this time. The summation of these contractions of smooth muscle
      contractions in the microcirculatory bed maintains their vascular tone and yields
      the pattern of EV. The paper also describes the earlier unknown properties of
      hemoglobin and myoglobin to cause smooth muscle spasm and to accelerate platelet
      destruction. A correlation between the EV and vascular platelet hemostasis is
      described in terms of these properties. The continuous mechanism of EV is
      impaired and it transforms to intermittent (final) vascular platelet hemostasis.

PMID- 7522695
TI  - [Pancreatic surgery: results and perspectives].

PMID- 7522694
TI  - [Evaluation of portal circulation in healthy subjects with duplex scanning before
      and after meal].
AB  - Duplex scanning was used to functionally assess the arterial and venous vascular
      bed in the portal circulatory system in 11 healthy persons aged 17 to 22 years
      before and after taking the food containing normal levels of calories. A
      circulatory response was studied in the celiac trunk, superior mesenteric artery,
      splenic and portal veins. The normal values of the diameter, linear and
      volumetric blood flow velocities of the vessels under study were defined. There
      was their increased velocity of arterial and venous flows. A nevous response to a
      meal was ahead of an arterial one and the increase in blood flow in the celiac
      trunk occurred more rapidly than in the superior mesenteric artery. It is
      concluded that duplex scanning is an informative and reliable tool in the study
      of blood flow in the portal circulatory system.

PMID- 7522696
TI  - [Improvement of results in extensive liver resections].

PMID- 7522698
TI  - [Progress in scientific achievements at the Institute of Surgery A.V. Vishnevsky
      of the Russian Academy of the Medical Sciences].

PMID- 7522697
TI  - [Signal-transducing ATP -- mediator of transmembranous transmission of mitogenic
      signals to cellular growth].
AB  - The paper summarizes the experimental data obtained by the author and his
      collective body on studies into the author's discovered cellular phenomenon-
      rapid living cellular plasma membranous generation and utilization of short-lived
      signal-transducing ATP as a transmembranous mitogenic signal-to-cellular growth
      transmitter by growth factor receptors associated with tyrosine kinase. It
      considers the conditions of the generation, cellular localization, possible
      mechanism of signal ATP on the plasma membrane of a living cell. It also
      emphasizes that there is a correlation between the generation of a short-lived
      signal-transducing ATP from ADP and inorganic phosphate and the oxidation of
      NAD.H with oxygen conjugated with proton-activated, sodium-translocating
      phosphorylation.

PMID- 7522700
TI  - [Skin expansion in the reconstructive and plastic surgery of burns].

PMID- 7522699
TI  - [Omentoplasty and myoplasty on a fixed vascular pedicle in the treatment of
      complications in thoracic surgery].
AB  - A total of 37 patients with postoperative chronic osteomyelitis of the sternum
      and ribs which had developed after various operations on chest organs and 22
      patients with residual pleural empyema developed after various lung operations
      were followed up. In patients from the both groups the first step, a thorough
      sanitation of infection foci, was performed; resection of diseased segments of
      the sternum and ribs in sternal and costal osteomyelitis and sanitation of the
      residual pleural cavity in residual pleural empyema. The second step was that
      defect of the anterior surface of the chest, which had developed after sternal
      and costal resection, was eliminated in the first group of patients as well as
      residual pleural cavity and bronchial fistula were removed in the second group.
      In the two groups, the following tissues were used as a plastic material: a
      greater omental flap (n = 27), the musculus rectus abdominis (n = 7), and
      musculus pectoralis major (n = 3) in Group 1, a greater omental flap (n = 8), the
      musculus pectoralis major (n = 9) and musculus latissimus dorsi (n = 5) in Group
      2. In Group 1 a good therapeutical result was noted in 34 (91.1%) patients, a
      satisfactory one in 2 (6.2%). One (2.7%) patient died. It is concluded, that
      displacement of tissues on the fixed vascular pedicle is a valid method for
      eliminating tissue deficit in thoracic surgery.

PMID- 7522702
TI  - [Results of laparoscopic cholecystectomy].
AB  - The paper provides the results of two-year use of laparoscopic cholecystectomy as
      a treatment of calculous cholecystitis in patients with various clinical and
      morphological types of calculous cholecystitis. Less intraoperative trauma, a
      mild postoperative period, and early activization of patients, good cosmetic
      effect are indisputable advantages of this therapeutical method which is an
      alternative to an open operation for calculous cholecystitis.

PMID- 7522701
TI  - [Staged tissue expansion in the surgery of suppurative wounds].
AB  - To close extensive infected wounds and to replace long bone defects, along with
      other methods a method of graded tissue strain (GTS) has been developed and
      introduced into practice (246 patients). The method differs from all others in
      that it requires no transfer of elaborate flaps while replacing soft tissue
      defects; and no graft or foreign body is introduced externally into the wound in
      replacing long bone defect. Soft tissue defect is gradually replaced by wound
      adjacent intrinsic tissues, the wound is closed by related skin and bone defect
      is filled by an osseous regenerate which is formed during graded transposition of
      the osteotomized fragment. At the same time good blood supply and tissue
      innervation retain, which contributes to their resistance to purulent infection.
      The analysis of the findings has led to the conclusion that GTS is an
      indispensible contribution to the development of plastic purulent surgery
      allowing the anatomic and functional integrity of the diseased segment to be
      restored.

PMID- 7522703
TI  - [Computed tomography in the comprehensive radiologic diagnosis of chronic
      osteomyelitis of the lower extremities and pelvis].
AB  - The role of computed tomography in multimodality radiation diagnosis was assessed
      in the treatment of chronic osteomyelitis of the lower extremity and pelvis in
      218 patients (128 with posttraumatic osteomyelitis, 46 with hematogenic
      osteomyelitis of long bones, and 19 with chronic pelvic osteomyelitis) aged 16-78
      years. Computed tomography was used to specify the symptomatology of chronic
      osteomyelitis, to define indications for radical surgical treatment. The soft
      tissues of the shin were studied in patients with chronic osteomyelitis versus
      lymphedema in 103 patients, post-thrombophlebitic syndrome in 17, acute wound
      infection in 9. The symptomatology of osseous regenerate in distraction
      osteosynthesis was studied (120 computed tomograms). It has been indicated that
      computed tomography is effective in studying the chronic osteomyelitis-inflicted
      extremity and pelvis in the pre- and postoperative periods.

PMID- 7522705
TI  - [Phenotypic and morphologic changes of connective tissue and atherosclerosis of
      coronary arteries].

PMID- 7522704
TI  - [Use of dalargin in the intensive therapy of critical conditions].
AB  - The paper analyzes whether the national synthetic leukenkephalin analogue
      dalargin can be used in the prevention and treatment of postoperative polyorgan
      deficiency. Dalargin has been experimentally demonstrated to be effective in
      preventing impairments in transcapillary fluid exchange, by stopping the
      development of pulmonary edema. The use of the drug in the intra- and
      postoperative period in patients undergone cardiac surgery during general
      assisted circulation reduced the incidence substantially and decreased the
      severity of respiratory distress syndrome. The experimental and clinical findings
      suggest that dalargin has pulmono-, hepato-, and pancreatoprotective properties.
      Thus, dalargin should be used in the multimodality intensive care of
      postoperative polyorgan deficiency.

PMID- 7522707
TI  - [Theoretical and practical aspects of using cultured fibroblasts for skin
      reconstruction].

PMID- 7522708
TI  - [Mortality and lethality of influenza and acute respiratory diseases].
AB  - Analysis of mortality and lethality rates due to influenza, acute respiratory
      disease (ARD), and acute pneumonia in adults has revealed a higher proportion in
      an old-age group (over 60 years) than in younger-age ones (15-30-year olds).
      Moreover, these figures have been found to have increased twice in the old-age
      group in the last two decades. At the same time the lethality rates due to acute
      pneumonia have been reported to be 8-12 times higher in inpatients over 60 years
      of age (a high-risk group) than those in younger adults and 3-4 times higher than
      those in the middle-age group. The extremely severe course of pneumonia
      associated influenza characterized by toxicosis, pulmonary and cardiovascular
      insufficiency has been observed in most death victims.

PMID- 7522706
TI  - [Immunobiologic characteristics of hybrid proteins consisting of tumor necrosis
      factor alpha and thymosin alpha 1].
AB  - The preparations of alpha 1-thymosin (T), alpha-tumor necrotic factor (TNF) and
      their based hybrid proteins: T-TNF, TNF-T, and T-TNF-T were studied by using a
      wide spectrum of immunobiological tests. In the L-929 cells, T-TNF preserved
      cytotoxicity unique to TNF; TNF-T preserved it 10 times less, and T-NTF-T was
      completely inactive. TNF-T inhibited the growth of Molt-4, Jm-9, Raji cells by 63
      = 84%, and TNF suppressed only Raji cells by 50%. Hybrid proteins caused cell
      proliferation of the thymus, spleen, and lymph nodes; H-2K, CD4, and CD8
      differently increased the expression of thymocytic antigens. The authors found
      the different effects of the drugs on phagocytosis, the production of antibody
      forming cells, delayed reaction, and activation of natural killer cells. The
      protein T-TNF-T produced the most pronounced action.

PMID- 7522709
TI  - Euthanasia. More palliative care is needed.

PMID- 7522711
TI  - Immunohistochemical demonstration of tenascin and fibronectin in odontogenic
      tumours and human fetal tooth germs.
AB  - The distribution of tenascin and fibronectin (plasma fibronectin) was studied
      immunohistochemically in ameloblastomas, ameloblastic fibromas and ameloblastic
      carcinomas, as well as in tooth germs using monoclonal antibodies. Tenascin is an
      extracellular matrix molecule that was shown to be enriched in the embryonic
      mesenchyme surrounding the budding epithelium in various organs, including the
      tooth. Tenascin was strongly expressed in the basement membrane zone of the
      ameloblastomas and in the early tooth germ and the dental lamina, but not in the
      dental follicle. The expression of tenascin in the ameloblastic fibroma was seen
      in the basement membrane of the epithelial islands throughout the stromal
      tissues. There were clear differences in fibronectin expression in the follicular
      ameloblastoma and ameloblastic carcinoma. The results suggest that tenascin and
      fibronectin are involved in epithelial mesenchymal interactions of the tooth germ
      and in odontogenic tumours.

PMID- 7522710
TI  - Intermediate filaments in oral neoplasia. I. Oral cancer and epithelial
      dysplasia.
AB  - The major value of intermediate filaments (IFs) in biological and applied
      research lies in their high order of cell and tissue specificity. This is
      particularly well illustrated in keratin (K) expression in various oral
      epithelia. Although the original class of IF is usually conserved in tissues
      after neoplastic transformation, epithelia show a tendency to shift their pattern
      of keratin expression in a manner which, while not predictable with precision,
      may sometimes be of diagnostic or prognostic significance. This review compares
      the keratins in normal oral epithelia, which show a mainly site-dependent
      expression, with those in squamous cell carcinoma. Key changes in the latter are
      the presence of simple epithelial keratins, K8 and K18 (occasional K7), reduced
      expression of differentiation-linked keratins (K1, K10, K4 and K13) and a
      tendency for down-regulation of primary keratins, K5 and K14. Moderate and severe
      dysplasias also tend to exhibit K8 and K18 with concomitant disordered expression
      of differentiation-linked keratins. There are reports of similar changes after
      neoplastic transformation in other mucosal sites and skin. Before this
      information can be applied diagnostically in immunocytochemical studies, the anti
      keratin antibodies must be fully characterised and their interaction with the
      relevant tissue, both frozen and conventionally processed, should be evaluated.

PMID- 7522714
TI  - Cerebral distribution of the B-36 VDAC protein in rat, cow and man brain:
      immunocytochemical study.
AB  - Polyclonal antiserum to a new voltage-dependent anion channel protein (B-36 VDAC)
      isolated during the purification of the GABAA receptor from bovine cerebral
      cortex was used to determine the localization of this protein in
      immunocytochemical preparations of cerebral cortex, cerebellum and hippocampal
      formation of rat, cow and human. The labeling was present in the Purkinje cells
      and some cells of the molecular layer of the rat cerebellum, as well as in
      pyramidal and non-pyramidal cells of the rat and human cerebral cortex; the
      labeling outlined the membrane surface. In the rat granule cells of the dentate
      gyrus and the pyramidal cells, the labelling was observed within the cells. These
      results indicate that the B-36 VDAC protein is heterogeneously distributed among
      different cerebral regions in different species and suggest that this protein
      would be associated with the alpha-1 subunit of the GABAA receptor
      (benzodiazepine binding sites).

PMID- 7522715
TI  - Specific ligation of the HIV-1 viral envelope protein gp120 on human CD34+ bone
      marrow-derived progenitors.
AB  - The precise mechanisms of hematologic abnormalities observed during HIV infection
      remain unknown. In vitro experiments performed by various authors concerning the
      HIV toxicity on bone marrow-derived precursors did not allow them to determine
      whether this toxicity could be mediated through direct or non-direct effects,
      since it is today unclear if gp120 possesses a direct hematotoxic effect on human
      bone marrow progenies. The aim of our study was to determine whether labelled
      gp120 could specifically bind to the membrane of purified human normal CD34+
      cells and to investigate the in vitro effect of the gp120 on their growth. To
      answer these questions, human CD34+ cells were purified from normal bone marrow
      samples, then labelled with monoclonal antibodies directed either against CD4
      antigen or CD34 antigen and/or with FITC labelled gp120 and analyzed by FACS. Our
      results demonstrate the presence of about 5% of CD4+CD34+ cells and of nearly 12%
      of CD34+gp120+ precursors. Together with our results concerning the in vitro
      inhibitory effect of gp120 on the growth of the same purified CD34+ precursors,
      our data demonstrated the direct hematotoxic activity of HIV-derived gp120 and
      the possible HIV infection of hematopoietic progenitors through the interaction
      of gp 120 with CD34+ cell surface.

PMID- 7522713
TI  - IgE-dependent activation of Fc epsilon RII/CD23+ normal human keratinocytes: the
      role of cAMP and nitric oxide.
AB  - Epidermal keratinocytes (EK) are exposed to multiple inflammatory stimuli and
      paracrine factors secreted by various dermal cells (lymphocytes, mast-cells,
      macrophages, fibroblasts) during wounding, cutaneous allergy and infections. We
      have previously demonstrated that following stimulation with interleukin-4 (IL-4)
      or interferon-gamma, human EK express the low affinity receptor for IgE (Fc
      epsilon RII/CD23) on their surface. In the present study, we showed that the
      ligation of CD23 by IgE/anti-IgE immune complexes or specific monoclonal
      antibody, induces a dose-dependent release of interleukin-6 and tumor necrosis
      factor-alpha from EK. CD23-ligation activates the nitric oxide-dependent pathway,
      as demonstrated by the high levels of nitrites released in cell supernatants, and
      the accumulation of intracellular cyclic nucleotides in EK. These second
      messengers are required for IgE-dependent stimulation of cytokine production by
      these cells, as this is completely abolished by cAMP or NO synthase antagonists.
      Human epithelial keratinocytes may thus participate in IgE-mediated immune
      responses, through their ability to express functional CD23 antigen.

PMID- 7522712
TI  - The expression of the penicillin G amidase gene of Escherichia coli by primer
      extension analysis.
AB  - Escherichia coli ATCC 11105 and JM109, transformed with a multicopy plasmid
      carrying the penicillin G amidase (PGA) gene, were grown at 26 degrees and 37
      degrees C, in the presence or the absence of phenylacetic acid (PAA) or of
      glucose. A method based on primer extension was developed to quantify in vivo
      levels of PGA mRNAs. A unique transcription start site was found to be used in
      all the fermentation conditions tested. This site is located 28 nucleotides
      upstream of the initiation codon. Its utilization is subjected to catabolic
      repression and is induced by PAA. This site is used at 37 degrees C, but the PGA
      mRNA level in E. coli ATCC 11105 is lower at 37 degrees C than at 26 degrees C.
      Induction of the pga gene by PAA was found to be more efficient in the producer
      strain. Taking into account the amount of PGA mRNA present in the cells at 37
      degrees C, one would expect the production of active PGA at this temperature.
      This is not the case. Thus, at 37 degrees C, expression is blocked at a step
      after transcription.

PMID- 7522716
TI  - Serotonin receptors and therapeutics.
AB  - Since its discovery, serotonin (5-hydroxytryptamine = 5-HT) has become a major
      player on the neurotransmitter "stage". Multiple receptor subtypes for 5-HT have
      been identified and classified, and a vast pharmacology of 5-HT has emerged. In
      particular, 5-HT has been shown to exert marked effects on the cardiovascular
      system, central nervous system (CNS) and gastrointestinal (GI) tract, and
      important ligands have been developed that mimic or block its action selectively.
      Furthermore, drugs that release 5-HT, and others that prevent its uptake, have
      been developed. This brief review focuses on the pharmacology of 5-HT agonists
      and antagonists that exhibit, at least partly, clinical relevance.

PMID- 7522717
TI  - Biphenotypic M0 acute myeloid leukemia with trisomy-4.
AB  - We report here a rare case of biphenotypic M0 acute myeloid leukemia (AML)
      associated with trisomy 4. The literature of trisomy 4 in acute leukemia was
      reviewed. M2 and M4 AML are the most common FAB subtypes associated with trisomy
      4. The clinical course of this entity is generally comparable with other non
      trisomy 4 cases of AML. Despite the speculation made when first described, no
      specific environmental toxin has been found to be associated with this entity. C
      kit oncogene has been mapped to chromosome 4 recently, and the role of this proto
      oncogene in leukemogenesis of trisomy 4 associated leukemia should be further
      investigated.

PMID- 7522718
TI  - Integrins and adhesive receptors in normal and leukemic CD34+ progenitor cells:
      potential regulatory checkpoints for cellular traffic.
AB  - Multiple adhesion receptors are involved in the interaction of hematopoietic
      cells with the marrow microenvironment. This work characterizes the expression of
      various adhesive receptors on normal early hematopoietic precursors and reviews
      how they might be altered in leukemic states. Early hematopoietic CD34+ cells
      express CD18, CD11a, CD49d, CD49e, CD44, ICAM-1, and ICAM-3. Likewise, most AML
      samples express CD49d, CD49e, and CD44. In addition to mediating the adherence of
      progenitors to the marrow, these multiple receptors and their respective ligands
      may serve to regulate in vivo leukemic cell agrees from marrow and the ability of
      certain leukemic phenotypes to selectively seek extramedullary sanctuary sites
      such as the skin and the central nervous system.

PMID- 7522720
TI  - Impaired proliferation and differentiation of myelodysplastic CD34+ cells.
AB  - The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders of
      hematopoiesis entailing hyperproliferative and ineffective hematopoiesis
      resulting in refractory cytopenia(s), and increased risk of transformation into
      acute myeloblastic leukemia (AML). The widely used classification defined by the
      French-American-British group (FAB) recognizes 5 cytological subtypes of
      different prognosis, based essentially on the presence and the frequency of
      marrow blasts. The percentage of marrow blasts does not exceed 30%, hence, direct
      investigations of biological and biochemical events of MDS blast cells have been
      hampered. The CD34 antigen is currently unique in its narrow specificity of
      expression on human lymphohematopoietic progenitor cells. This cell membrane
      phosphoglycoprotein has been used for immunologic blast cell purification,
      notwithstanding the frequency of marrow blasts, and has provided a set of tools
      for investigations of MDS i.e. a direct comparison of the nature of blast cells
      in each of the MDS subtypes, using immunologic, biologic, biochemical and
      molecular biological methodology. A combination of serum-free medium and a
      purification method for blast cells provided evidence that the progenitor cell
      growth abnormalities in these disorders involve a defect in the capacity of
      progenitor cells to respond to stimulation with growth factor(s), and has
      presented direct evidence for the manner in which myelodysplastic CD34+ cells are
      impaired.

PMID- 7522723
TI  - Rapid RT-PCR amplification from limited cell numbers.
AB  - We describe a rapid and efficient RT-PCR method particularly suited to procedures
      involving limited cell and target gene copy numbers. Purified leukocytes and
      myeloid colonies derived from patients with chronic myelogenous leukemia (CML) in
      chronic phase were used for direct RT-PCR. Purified cells and colonies were lysed
      using a small quantity of DEPC-treated water containing RNasin as an RNA
      inhibitor. The untreated lysate was either used immediately for RT-PCR or frozen
      at -70 degrees C for later use. By this method we were able to consistently
      amplify bcr-abl transcripts from as few as 10 cells. No noticeable difference was
      observed between products amplified from fresh and frozen samples.

PMID- 7522719
TI  - CD56 (NCAM)-positive malignant lymphoma.
AB  - CD56, a natural killer cell marker reactive with the neuronal-cell adhesion
      molecule (NCAM), identifies a group of lymphomas with distinctive
      clinicopathologic features. The disease affects mostly middle-aged adults who
      often present with fever, skin rash and hepatosplenomegaly in the absence of
      peripheral lymphadenopathy. Extranodal involvement is common, particularly the
      skin, aerodigestive tract and central nervous system. Histologically, an
      angiocentric and angiodestructive pattern of infiltrate is often seen, but the
      cytological spectrum of the lymphoma cells is very broad. Cytoplasmic granules,
      however, are frequently found when Giemsa-stained cytologic preparations are
      examined. Immunologically, CD56-positive lymphomas can be sub-classified into CD3
      positive (T-cell) and CD3-negative (probably true natural killer cell) subtypes.
      T-cell receptor gene rearrangement can be demonstrated in the former cases, but
      not in the latter. Clinically, CD56-positive lymphomas are aggressive neoplasms.

PMID- 7522724
TI  - Phosphopeptide binding to the N-terminal SH2 domain of the p85 alpha subunit of
      PI 3'-kinase: a heteronuclear NMR study.
AB  - The N-terminal src-homology 2 domain of the p85 alpha subunit of
      phosphatidylinositol 3' kinase (SH2-N) binds specifically to phosphotyrosine
      containing sequences. Notably, it recognizes phosphorylated Tyr 751 within the
      kinase insert of the cytoplasmic domain of the activated beta PDGF receptor. A
      titration of a synthetic 12-residue phosphopeptide (ESVDY*VPMLDMK) into a
      solution of the SH2-N domain was monitored using heteronuclear 2D and 3D NMR
      spectroscopy. 2D-(15N-1H) heteronuclear single-quantum correlation (HSQC)
      experiments were performed at each point of the titration to follow changes in
      both 15N and 1H chemical shifts in NH groups. When mapped onto the solution
      structure of the SH2-N domain, these changes indicate a peptide-binding surface
      on the protein. Line shape analysis of 1D profiles of individual (15N-1H)-HSQC
      peaks at each point of the titration suggests a kinetic exchange model involving
      at least 2 steps. To characterize changes in the internal dynamics of the domain,
      the magnitude of the (15N-1H) heteronuclear NOE for the backbone amide of each
      residue was determined for the SH2-N domain with and without bound peptide. These
      data indicate that, on a nanosecond timescale, there is no significant change in
      the mobility of either loops or regions of secondary structure. A mode of peptide
      binding that involves little conformational change except in the residues
      directly involved in the 2 binding pockets of the p85 alpha SH2-N domain is
      suggested by this study.

PMID- 7522722
TI  - The use of the PCR to quantitate gene expression.

PMID- 7522721
TI  - Prognosis of high dose chemotherapy/autologous bone marrow transplantation
      candidates not receiving this treatment after failure of primary therapy of
      Hodgkin's disease.
AB  - In a multicenter study on the therapy of Hodgkin's disease, in 88 out of 297
      patients with primary advanced stages IIIB/IV, a failure to the treatment with
      the alternating chemotherapy COPP/ABVD +/- radiation was recorded. The cause of
      failure was as follows: tumor progression under current therapy (PD) 23/88,
      partial response at the end of therapy (PR) 28/88, early nodal relapses 13/88,
      late nodal relapses 16/88, extranodal relapses 7/88, undetermined localization
      1/88.36 months after manifestation of the failure to treatment, 45% of all
      patients were still alive. In cases of primary PD the prognosis was the worst of
      all. Only 1/23 of these patients received a long-term continuous complete
      remission (cCR) with the salvage therapy. 11 patients with only a nodal relapse
      received a cCR with irradiation alone. These cases could be regarded as low risk
      relapses. For the high risk relapse group (n = 57) an indication for high dose
      chemotherapy with subsequent autologous bone marrow transplantation (HDC/ABMT)
      would have been imperative, following the present-day definition. The probability
      of survival of these patients who, however, only received a conventional salvage
      therapy was up to 38% (95% confidence interval 22-54%). Comparing these data with
      the literature our results seem not to be substantially worse than those for
      patients who underwent HDC/ABMT. Only in a randomized comparison can the decision
      be made on whether HDC/ABMT would be superior to high dose conventional
      chemotherapy supported by hematopoietic growth factors. It is suggested that such
      a therapy study be performed as soon as possible.

PMID- 7522725
TI  - [Cyfra 21-1 new marker for non-small cell lung cancer].
AB  - The aim of the study is to estimate the new tumor marker CYFRA 21-1 in non-small
      cell lung cancer (NSCLC) patients and comparison of this results with SCC-Ag. The
      investigation was carried out on 115 NSCLC patients (55 with squamous cell, 35
      with adenocarcinoma, 25 with large cell) qualified for surgical treatment and in
      48 nonmalignant lung diseases patients. CYFRA 21-1 was determined by the means of
      IRMA method (CIS bio international--GIF-SUR-Yvette, France) and SCC-Ag--MEIA
      method (IMx system Abbott). Elevated levels of CYFRA 21-1 were obtained in 48.7%
      and SCC-Ag in 39.1%. Elevated levels of examined markers most frequently occurred
      in squamous cell type (SCC). It was found out that CYFRA 21-1 dependent on: a)
      SCC stage (I-40%, II-61.1%, III-85.2%), b) tumor size (T1-38.4%, T2-73.1%, T3
      87.5%), c) mediastinal lymph nodes metastases (No and N1-53.8% and N2-86.9%).
      Similar correlations were not observed in SCC-Ag examination. Simultaneous
      determination of CYFRA 21-1 and SCC-Ag showed minimal sensitivity increase from
      48.7% to 52.1% in NSCLC and from 69.1% to 70.1% in SCC and decrease of
      specificity from 95.8% to 85.4%. To sum up, determination of CYFRA 21-1 in NSCLC
      patients (especially in SCC patients) is useful in diagnosis and clinical stage
      determination.

PMID- 7522726
TI  - [Diagnostic difficulties in systemic lupus erythematosus].
AB  - A case of SLE in female 43 years old is presented. The patient was hospitalized
      with diagnosis of pneumonia. The correct diagnosis was made after LE-cell and
      antinuclear antibodies in blood serum were found. After the treatment with small
      prednisone doses the long years remission was given. In discussion the diagnosis
      difficulties and basis diagnosis are presented.

PMID- 7522727
TI  - Autologous bone marrow transplantation for myeloma patients using PNA- and CD19
      purged marrow rescue.
AB  - A new method of in vitro bone marrow purging using a lectin and monoclonal
      antibody in combination has been used for the first time in vivo. Two patients
      with advanced myeloma were treated with high-dose melphalan and total body
      irradiation and then rescued with autologous bone marrow which had been purged in
      vitro to remove malignant cells by using a combination of a plasma cell-binding
      lectin (peanut agglutinin, PNA) and the anti-B lymphocyte monoclonal antibody
      anti-CD19, bound to magnetised microspheres. Both patients showed rapid
      engraftment of the purged bone marrow and remain well 36 and 46 months later with
      normal bone marrow morphology, although one patient still has a low level of
      circulating paraprotein. This is a promising form of therapy for what has been an
      invariably fatal condition.

PMID- 7522728
TI  - National Advisory Committee on Immunization (NACI). Statement on influenza
      vaccination for the 1994-95 season.

PMID- 7522729
TI  - Measurement of staphylokinase by enzyme-linked immunosorbent assay using
      monoclonal antibodies.
AB  - Hybridoma clones producing monoclonal antibodies specific for staphylokinase were
      isolated. A competitive assay revealed that the monoclonal antibodies studied
      could be divided into at least two groups. Representatives of these groups, AS22
      and B3E6, recognized quite different epitopes on staphylokinase. This finding led
      us to develop an assay system for the quantitative analysis of staphylokinase by
      enzyme-linked immunosorbent assay using AS22 as the capturing antibody and
      biotinylated B3E6 as the "detector". The lower limit of sensitivity of the assay
      was 20 pg of staphylokinase per ml. The assay exhibited good reproducibility,
      with values of 5.8 and 3.8% for the intra- and inter-assay coefficients of
      variation, respectively. Staphylokinase could be assayed in the presence of human
      plasma when the plasma was diluted more than 320-fold, and the measurement was
      unaffected by the presence of physiological concentrations of human plasminogen.
      Hence, this assay was considered useful for the detection and quantification of
      staphylokinase in clinical samples.

PMID- 7522731
TI  - Inhibition of tumor angiogenesis and metastasis by a saponin of Panax ginseng,
      ginsenoside-Rb2.
AB  - We studied the effect of ginsenoside-Rb2 extracted from Panax ginseng on
      angiogenesis and metastasis produced by B16-BL6 melanoma cells in syngeneic mice.
      Intravenous administration of ginsenoside-Rb2 on day 1, 3 or 7 after tumor
      inoculation achieved a remarkable reduction in the number of vessels oriented
      toward the tumor mass, but did not cause a significant inhibition of tumor
      growth. The anti-angiogenic effect was dose-dependent ranging from 10 to 500
      micrograms/mouse. In contrast, intra-tumoral or oral administration of
      ginsenoside-Rb2 caused a marked inhibition of both neovascularization and tumor
      growth. Ginsenoside-Rb2 did not affect the growth of rat lung endothelial (RLE)
      cells, B16-BL6 melanoma cells or various types of murine normal cells in vitro.
      The invasion of RLE cells into the reconstituted basement membrane (Matrigel),
      which is considered to be an essential event in tumor neovascularization, was
      inhibited by ginsenoside-Rb2 in a concentration-dependent fashion, while
      ginsenoside-Rb2 did not inhibit the haptotactic migration of endothelial cells to
      fibronectin-substrate. Multiple administrations of ginsenoside-Rb2 after the
      intravenous inoculation of B16-BL6 melanoma cells resulted in a significant
      inhibition of lung metastasis as compared with the untreated control. These
      results suggest that the inhibition of tumor-associated angiogenesis by
      ginsenoside-Rb2 may partly contribute to the inhibition of lung tumor metastasis.

PMID- 7522730
TI  - Effects of calcium-binding proteins on histamine release from permeabilized rat
      peritoneal mast cells.
AB  - Among the calcium-binding proteins from chicken gizzard smooth muscle, smooth
      muscle calcium-binding protein 11 (SMCaBP 11), which is an EF-hand type calcium
      binding protein, can prevent Ca2+ dependent histamine release from permeabilized
      rat peritoneal mast cells. This activity appears to be specific since other
      calcium-binding proteins (CaBPs), including h-calcimedin, l-calcimedin,
      calmodulin and S100, had no inhibitory action. Approximately 40% of the histamine
      release was inhibited by SMCaBP 11 at 48 nM and the half-maximal inhibition
      occurred at 20 nM. Immunological techniques revealed that permeabilized mast
      cells elicited by Ca2+ also released actin into the medium, but not tubulin. The
      addition of SMCaBP 11 prevented the secretion of actin from the mast cells,
      though the distribution of F-actin was only slightly affected. These findings
      suggest that SMCaBP 11 may modulate Ca2+ and actin-mediated exocytosis from
      permeabilized mast cells.

PMID- 7522732
TI  - Superoxide anion-induced histamine release from rat peritoneal mast cells.
AB  - We investigated the properties of superoxide anion (O2-)-induced histamine
      release from rat peritoneal mast cells using superoxide anion radicals obtained
      from potassium superoxide (KO2). KO2 elicited a rapid histamine release in a dose
      dependent fashion, without lactate dehydrogenase (LDH) release. The KO2-induced
      release was temperature- and energy-dependent. KO2 rapidly increased the
      intracellular free Ca2+ concentration, accompanied by a marked increase of Ca(2+)
      uptake. These findings indicate that the increase in intracellular Ca2+
      concentration is involved in the initiation of KO2-induced histamine release, and
      KO2 could be used as an agent of O2(-)-induced biological reactions.

PMID- 7522733
TI  - Antimetastatic effect of yeast mannan-bleomycin conjugate against mouse Lewis
      lung carcinoma.
AB  - A conjugate of bleomycin (BLM) and the mannan of bakers' yeast (Saccharomyces
      cerevisiae wild type strain) (WNM) was synthesized. The assay of its
      antimetastatic effect on Lewis lung carcinoma (3LL) implanted in C57BL/6 mice
      showed that this conjugate exhibited a higher antimetastatic effect and longer
      life-span elongation than those of free bleomycin and mannan with corresponding
      doses. This conjugate was also found to kill the 3LL cells in vitro. 14C-Labeled
      mannan-bleomycin conjugate was much more bound than 14C-labeled dextran-bleomycin
      conjugate to the 3LL. It was concluded that the anti-cancer mechanism of this
      conjugate, WNM-BLM possessed a specific binding effect to the tumor cells and
      exhibited a cytocidal effect on the 3LL target cells.

PMID- 7522735
TI  - Interaction of cells of Helicobacter pylori with human polymorphonuclear
      leucocytes: possible role of haemagglutinins.
AB  - The interaction of fluorescein isothiocyanate (FITC)-labelled cells of
      Helicobacter pylori with human polymorphonuclear leucocytes (PMNs) was studied.
      Two strains with surface haemagglutinins expressing different receptor
      specificity were used in order to decide if cell surface haemagglutinins of H.
      pylori may play a role in lectin-mediated binding to/uptake by phagocytes: (1)
      strain 17874 (NCTC 11637) which expresses sialic acid-specific haemagglutinin;
      and (2) strain 17875 (NCTC 11638) which expresses a sialic acid-independent
      haemagglutinin. Cells of strain 17874 were poorly attached to/ingested by PMNs
      compared to cells of strain 17875. Pre-treatment of bacteria with fetuin or
      rabbit antibodies against partly purified sialic acid-specific haemagglutinin
      enhanced interaction of cells of strain 17874 with PMNs. The enhancement did not
      occur in the case of strain 17875. Phagocytosis of H. pylori 17874 bacteria was
      slightly increased by fresh human sera positive for anti-H. pylori antibodies.
      The results suggest that the sialic acid-specific haemagglutinin complex of 17874
      bacteria might disturb their uptake by human PMNs.

PMID- 7522734
TI  - Binding of vitronectin and plasminogen to Helicobacter pylori.
AB  - We have studied how some extracellular matrix proteins, fibronectin, fibrinogen,
      collagen type I and type IV, plasminogen and vitronectin bind to Helicobacter
      pylori. Radiolabelled vitronectin and plasminogen bound to the haemagglutinating
      H. pylori strain 17874 at a high level (53% and 32%, respectively), type IV
      collagen showed an intermediate level of binding (16%), while binding by 125I
      labelled fibrinogen, fibronectin and collagen type I remained at a low level (5
      7%). Both 125I-vitronectin and plasminogen showed a dose-dependent binding to
      cells of H. pylori 17874. Plasminogen binding by this strain was specific since
      the binding was inhibited by nonlabelled plasminogen, but not by highly
      glycosylated glycoproteins such as fetuin and orosomucoid or by a variety of
      monosaccharides. We have previously shown that 125I-vitronectin shows a specific
      and saturable binding to H. pylori 17874, and that sialic acid-rich glycoproteins
      such as fetuin and orosomucoid drastically reduced binding. We now report that a
      simultaneous incubation of 125I-vitronectin and 125I-plasminogen with cells of H.
      pylori 17874 showed a total binding approximately similar to the level of binding
      when either 125I-plasminogen, or 125I-vitronectin only were incubated with the
      bacterial cells. Nonlabelled vitronectin inhibited the binding of 125I
      plasminogen by H. pylori, but nonlabelled plasminogen had no effect on the
      binding of 125I-vitronectin. Our findings suggest that there are different but
      probably closely localized binding sites for vitronectin and plasminogen on H.
      pylori 17874.

PMID- 7522736
TI  - [Twenty-eight-day repeated dose toxicity test of Ajicoat SPG and Bionole in
      Wistar rat].
AB  - A twenty-eight-day repeated dose toxicity test of Ajicoat at dose levels of 0,
      0.05, 0.2 or 1.0% and Bionole at dose levels of 0.2, 1.0, or 5.0% in the feed was
      carried out in male and female Wistar rats. Three groups, at the dose levels of
      1.0% of Ajicoat, 5.0% of Bionole and control groups, were used for investigation
      of recovery. No animals died during the administration period. There were no
      significant differences in body weight gain, food consumption and organ weight
      between the treated and control groups. No specific changes were observed in any
      parameters of hematological investigations. At doses higher than 1.0% of Ajicost
      and Bionole groups, a significant increase of BUN value in serum was observed in
      both sexes. The serum glucose value increased and NEFA value decreased in male at
      a dose of 1.0% of Ajicoat group. These changes observed at the end of the
      administration period were no longer detected after the recovery period,
      suggesting that these effects were reversible. On histopathological examination,
      no specific changes were observed in the Ajicoat and Bionole treated rats. Based
      on these results, the no-observed-effect level was 0.2% (174 mg/kg) for both
      Ajicoat and Bionole.

PMID- 7522738
TI  - Assessment of children with developmental apraxia of speech: a rationale.
AB  - A rationale to guide assessment and subsequent management of children with
      developmental speech disorders is described. Hypotheses about the nature of
      praxis, the role of oral-verbal praxis in linguistic processing and speech
      development, and the effects of disturbances in praxis on speech behavior are
      presented. Implications of a diagnosis of developmental apraxia of speech (DAS)
      for treatment planning and expected speech, language, and social communication
      outcomes are discussed. Misconceptions about children diagnosed with DAS and
      assumptions underlying the author's approach to assessing children with DAS are
      identified. The desired functional outcome of the assessment approach advocated
      is a management plan that addresses the needs of the child and family and
      maximizes the child's ability to communicate.

PMID- 7522737
TI  - Assessment of children with developmental apraxia of speech: a procedure.
AB  - General considerations for the assessment process are presented. Then, six
      assessment goals are defined: (1) Determination of prerequisite behaviors for
      spoken language; (2) Assessment of current speech and language skills; (3)
      Definition of the nature and severity of the speech disability and the severity
      of the handicap; (4) Determination of the effects of facilitating approaches and
      treatment options; (5) Establishment of the child's prognosis; (6) Determination
      of the criteria for termination of treatment. Procedures, materials, and tests
      are described in relation to the assessment goals.

PMID- 7522739
TI  - Luteinizing hormone-releasing hormone receptor messenger ribonucleic acid
      expression in the rat pituitary during lactation and the estrous cycle.
AB  - To study mechanisms underlying the modulation of luteinizing hormone-releasing
      hormone receptor (LHRH-R) during lactation and the estrous cycle, we used a
      reverse transcriptase-polymerase chain reaction (RT-PCR) procedure to generate a
      probe for rat LHRH-R messenger RNA (mRNA). Using primers based on the mouse
      sequence, we amplified an approximately 300 bp fragment from rat pituitary
      complementary DNA. This PCR product was shown to be part of LHRH-R cDNA by direct
      sequencing and by comparing to the rat LHRH-R cDNA reported recently. Then, this
      PCR fragment was used as a probe for northern blotting analysis. The level of
      LHRH-R mRNA in the pituitary was significantly decreased during lactation, by
      approximately 80%, compared to that of ovariectomized and intact (diestrous and
      metestrous cycling) rats while no statistical difference in glyceraldehyde-3
      phosphate-dehydrogenase (GAPDH) mRNA level was observed between groups. During
      the estrous cycle, the level of LHRH-R mRNA in the pituitary was about two-fold
      higher on diestrous day 2 and the morning of proestrus than that on diestrous day
      1 and quickly returned toward control level by noon of proestrus. In addition, we
      found that GAPDH mRNA levels from a so-called housekeeping gene often thought to
      be unchanged under different conditions, were significantly higher on proestrus
      while levels of 18S rRNA were not significantly changed. The large decrease in
      LHRH-R mRNA during lactation could account for the changes in LHRH binding
      previously reported.

PMID- 7522740
TI  - Patch-clamp analysis of direct steroidal modulation of glutamate receptor
      channels.
AB  - Steroid hormones regulate the neuroendocrine and behavioral functions of the
      brain by using a number of diverse cellular mechanisms. Many steroids exert rapid
      electrophysiological effects on neurons, involving specific interactions with
      membrane components, such as neurotransmitter receptors. Previous studies suggest
      that the steroids, estrogen and pregnenolone sulfate (PS), might directly
      modulate glutamate receptors. The present experiments utilized patch-clamp
      recording of glutamate receptor-channels in excised membrane patches to test for
      direct modulation by these steroids. Characteristic single-channel activity from
      N-methyl-D-aspartate (NMDA) receptors could be elicited in both inside-out and
      outside-out patches excised from acutely dissociated hippocampal neurons. PS, but
      not 17 beta-estradiol, increased the open probability of NMDA channel activity in
      inside-out and outside-out patches. The PS-induced increase in open probability
      could be attributed to an increase in both frequency of opening and mean open
      time of the NMDA receptor, though the effect on frequency of opening was more
      prominent. The non-NMDA agonist, kainate, induced continuous shifts and increased
      noise in the baseline current of outside-out patches, but rarely activated
      clearly resolvable single-channel openings. 17 beta-estradiol and PS had no
      apparent effect on the kainate-induced currents. These findings suggest that some
      steroids can directly modulate glutamate receptors, but other steroids may
      utilize indirect mechanisms for regulating glutamatergic synaptic transmission.

PMID- 7522741
TI  - The rumpshaker mutation in spastic paraplegia.

PMID- 7522743
TI  - Critical review of the diagnosis of prostatic obstruction.

PMID- 7522742
TI  - Inactivation of E2a in recombinant adenoviruses improves the prospect for gene
      therapy in cystic fibrosis.
AB  - Although first generation recombinant adenoviruses, deleted of sequences spanning
      E1a and E1b, have been useful for in vivo applications of gene therapy,
      expression of the recombinant gene has been transient and often associated with
      the development of inflammation. We show that with first generation adenovirus
      mediated gene transfer to the mouse lung, viral proteins are expressed leading to
      destructive cellular immune responses and repopulation of the lung with
      nontransgene containing cells. Second generation E1 deleted viruses further
      crippled by a temperature sensitive mutation in the E2a gene were associated with
      substantially longer recombinant gene expression and less inflammation. Stable
      expression of human CF transmembrane conductance regulator has been achieved in
      lungs of CF mice instilled with a second generation virus.

PMID- 7522745
TI  - [Adaptation and validation in the French language of the International Score of
      Symptoms of Benign Prostatic Hypertrophy].
AB  - The International Prostate Symptom Score, which was proposed during the First
      Consultation on Benign Prostatic Hyperplasia in June 1991, was culturally adapted
      and linguistically validated in French. In a first step, the English version,
      adapted from the questionnaire developed by the American Urological Association,
      was translated into French. In a second step, the French version was submitted to
      a multidisciplinary group who made linguistic improvements. In a third step, the
      refined version was tested in 30 persons and amended. Finally, the questionnaire
      was submitted to a linguistic validation study in a representative sample of 100
      men aged 65 to 80. The use of this index will allow standardized measurements of
      urinary symptoms status in patients with benign prostatic hyperplasia.

PMID- 7522744
TI  - [Laparoscopically-controlled lymphadenectomy in localized cancer of the
      prostate].
AB  - Laparoscopic lymphadenectomy was performed among 15 patients. The average age was
      65.5 years. The group was made of 13 T2 and 2 T3. The average time of procedure
      was 175 min (90 a 240 min). The average number of lymph nodes removed
      laparoscopically from these patients was 5.3 on the left and 6.4 on the right.
      Metastatic nodes were found in 5 cases (33%) and among all these 5 patients the
      PSA level was above 30 and/or the Gleason score > 6. We noticed 3 major
      complications (2 bowel and 1 vascular injuries). Radical prostatectomy was made
      in 8 patients and nevertheless this intervention did not become more difficult.
      As a conclusion, this is a procedure which allows a good node staging but the
      complication rate is still high and will decrease with experience. The merits of
      such a method are still to be evaluated in localized prostatic cancer.

PMID- 7522748
TI  - [Immunotherapy with subcutaneous recombinant IL-2 and interferon combined with
      surgery in advanced stage carcinoma of the kidney].
AB  - Twelve consecutive patients with metastatic renal cell carcinoma were submitted
      to an integrate treatment plan of immunotherapy with subcutaneous IL-2 and IFN
      and radical surgery in a pilot study. Partial response were observed in 2
      patients, stable disease in 5 patients and progression of disease under treatment
      were observed in 5. Two RP were maintained for 12 and 18+ months and 1 SD is
      maintained at 12+ months. Treatment was well tolerated without significant
      toxicity. Integrated radical surgery and immunotherapy with s.c. IL-2 and IFN can
      produce occasionally protracted clinical responses.

PMID- 7522749
TI  - [The characteristics of the influences of the centromedian thalamus on the
      neuronal activity of the caudate nucleus].
AB  - Rearrangements of the unit activity in the thalamic intralaminar nucleus were
      found to be followed by reciprocal changes of activity of some neostriatal units.
      During avoidance conditioning, the activation of the centre median neurons is
      accompanied by the same firing pattern as in spontaneous activity. The features
      of organisation of the caudate nucleus seem to be basic.

PMID- 7522746
TI  - [Transurethral incision of the prostate. 5 years of follow-up. Apropos of 57
      patients].
AB  - Fifty-seven bladder neck incisions were studied with a minimum follow-up of 5
      years. The results published after one year were very satisfactory, but became
      more disappointing after 5 years, with a 38.7 reoperation rate. The weight of the
      prostate appears to be the determining factor. The indications, 5 years ago, were
      much wider than they are today, with prostate weights of up to 45 g on digital
      rectal examination. This type of operation should now be reserved for young
      subjects wishing to retain antegrade ejaculation with a prostate not exceeding 20
      to 30 g and in high surgical risk patients unsuitable for transurethral
      resection.

PMID- 7522747
TI  - [The economic evaluation of prostatic hyperthermia].
AB  - The aim of this study is to assess the hospital cost of treating Benign Prostatic
      Hyperplasia (BPH) by hyperthermia. The cost analysis was conducted simultaneously
      with a randomized clinical essay comparing hyperthermia to sham; the analysis was
      promoted by the Committee for Evaluation and Diffusion of Innovative Technologies
      (CEDIT) of the AP-HP. Cost components are: medical and paramedical staff
      salaries, supplies, overhead and capital costs. RESULTS: cost per session varies
      from FF 1200 to FF 5300; cost per treatment varies from FF 2500 to FF 9700
      depending upon the equipment used. For comparison, annual drug treatment of BPH
      varies from FF 2600 to FF 2900. CONCLUSION: important variation in the treatment
      cost of BPH by hyperthermia is observed depending on the equipment used. Clinical
      data do not demonstrate improved efficacy with the costlier hyperthermia
      treatments. Drug treatment seems to be more cost effective than hyperthermia for
      BPH treatment.

PMID- 7522750
TI  - [The behavioral and electrophysiological effects of the influence of the caudate
      nucleus on the spatial differentiation of conditioned-reflex stimuli].

PMID- 7522751
TI  - [The neurochemical characteristics of the rat neostriatum and motor cortex after
      the acquisition of a unilateral manipulatory reflex].
AB  - The activity of acetylcholinesterase (AChE), 5'-nucleotidase (NT) and adenylate
      cyclase (AC) were studied in sensomotor cortex and neostriatum (NS) from right
      and left hemispheres of control and experimental rats, trained to perform food
      reaching with pushing on operant by preferable forepaw. The levels of summarized
      bilateral activity of NT as well as of AC were found to be similar in both
      studied structures of control rats, while the activity of AChE was higher in NS
      than in cortex. In trained rats the activity of AC was decreased both in cortex
      and NS, the activity of NT was decreased in cortex and increased in NS, AChE
      being not changed when compared with control. The bilateral values of enzyme
      activities in well and badly learning rats were significantly different.
      Meanwhile, when the dominant and subdominant hemispheres were compared these
      values were found to be similar. In general, the results obtained could be
      evaluated as specific features of conditioned unilateral manipulatory reactions,
      characteristic for cortex and NS of brain hemispheres.

PMID- 7522752
TI  - [The reversibility of a blockade of corticofugal pulse trains to the neurons of
      the caudate nucleus in cats evoked by the neurotoxin MPTP].
AB  - In anesthetised cats, the number of the caudate nucleus neurons responding to a
      cortical stimulation with latency less than 8.0 ms, increased within 10-12 days
      after the MPTP administration and then gradually recovers by the 45th-54th day
      after the neurotoxin administration. Dopamine seems to exert a protecting
      inhibiting effect on transmission of corticofugal glutamatergic impulses
      travelling towards the neostriatum neurons.

PMID- 7522755
TI  - [The behavioral effects of dopamine agonists in rats following the intrastriatal
      administration of 6-hydroxydopamine].

PMID- 7522756
TI  - [Cortico-subcortical interactions in the process of emotional self-regulation
      under biological feedback control].

PMID- 7522754
TI  - [The strio-hypothalamic functional connections in pharmacologically evoked
      catalepsy in Wistar rats].

PMID- 7522757
TI  - [The participation of the cholinergic system of the dorsal and ventral striatum
      in regulating different forms of defensive behavior].

PMID- 7522753
TI  - [The nigrostrionigral system as an object for reconstruction by neural
      transplantation].

PMID- 7522758
TI  - [An analysis of the caudate-ventral tegmental effects in realizing motor-food
      conditioned reflexes in cats].

PMID- 7522760
TI  - [The striatum in birds (morphofunctional aspects)].

PMID- 7522761
TI  - [The insufficiency of frontal activation in parkinsonism].

PMID- 7522759
TI  - [The quantitative ultrastructural characteristics of the GABA-ergic synaptic
      terminals at the neurons of the reticular portion of the substantia nigra].

PMID- 7522762
TI  - [The transplantation of dissociated cells of the human embryonic midbrain into
      the striatum of adult rats].

PMID- 7522764
TI  - [The internal structural differentiation of the putamen in carnivores (the dog)
      and man].
AB  - The putamen tissue was found to have a complicated pattern of different
      structural fractions in its different parts. These seem to be special
      morphofunctional modules of the putamen comparable with cortical column
      fractions.

PMID- 7522763
TI  - [The effect of a blockade of the dopamine D2 receptors in the cat neostriatum on
      the neuronal background activity and reactions of the reticular portion of the
      substantia nigra related to saccadic eye movements].
AB  - In cats, the activity of the substantia nigra reticular part's neurons was
      extracellularly recorded prior to and after haloperidol administration into the
      head of the caudate nucleus. The number of neurons with burst-type firing
      increased after the administration from 34 to 61 per cent. The
      excitatory/inhibitory responses ratio associated with saccadic eyes movements
      also increased from 0.04 to 0.4. The above changes seem to follow a disinhibition
      of the GABA-ergic neurons under the effect of blockade of the neostriatum D2
      dopamine receptors.

PMID- 7522766
TI  - [The structure of the neuronal activity of the caudate nucleus in monkeys making
      a decision and realizing the motor program in different variants of a task of
      delayed spatial choice].
AB  - Spatial-selective neurons were found in the monkey caudate nucleus, the neurons
      being divided into two groups: one of them reflects the location of conditioned
      signals, the other--the direction of future motor response. The decision-making
      process is reflected in the unit activity in two aspects: as formation or choice
      of a concrete motor program, and as a transitory moment from instructive to
      executive phase of the behaviour.

PMID- 7522765
TI  - [General questions of the functioning of the basal ganglia].

PMID- 7522767
TI  - [The properties of the glucocorticoid receptors in the striatum and hypothalamus
      of rats selected for the threshold of excitability of their nervous systems].
AB  - In rats selected by their threshold sensitivity to electrical current, linear
      differences were found both at the receptor level and in stress-reactivity, the
      receptor lability being very high in the rats highly sensitive to electricity.
      The lower sensitivity rats were found to be more conservative in these
      parameters. The role of the hypothalamus and striatum in regulation of the
      hypophyseal-adrenocortical system through a feed-back mechanism, is discussed.

PMID- 7522768
TI  - [The afferent and efferent mechanisms enhancing the cholinergic activity of the
      neostriatum].

PMID- 7522770
TI  - [The role of the dopamine-reactive systems of the cortex and neostriatum in
      organizing situational conditioned reflexes].
AB  - The nigrostriatal dopamine-reactive (DA) system was shown to participate more in
      spatial analysis of conditioned signals, whereas the mesocortical DA system was
      rather more involved in the analysis of the signals' biological significance in
      dogs. The DA system of the caudate nucleus was involved in realisation of
      cognitive programs rather, whereas the putamen's DA system--in realisation of the
      motor ones. The coordinated activity of different levels of the DA system seems
      to be necessary for organization of the goal-directed behaviour.

PMID- 7522769
TI  - [Disorders in cognitive activity and their neuropharmacological correction in
      structural-functional failure of the head of the caudate nucleus in cats].
AB  - The caudate nucleus' head was shown to take part in organisation of praxis,
      perception, gnosis and "thinking activity". A wide range of dysfunctions in the
      caudate insufficiency was abolished by a specific set of psychotropic drugs
      acting upon classic neurotransmitter systems of the cat brain.

PMID- 7522771
TI  - [Glutamate receptor binding in the striatum of rats differing in the ability to
      learn].

PMID- 7522772
TI  - [Neurophysiological research on the characteristics of the status and functional
      activity of the formations of the striopallidum and thalamus in different forms
      of parkinsonism].

PMID- 7522773
TI  - [The organization of the afferent connections of the striatum--the structural
      basis for their functional specialization].

PMID- 7522774
TI  - [The reflection of the internal and external behavioral determinants in the
      neuronal activity of the monkey neostriatum].
AB  - The neostriatum neurons were shown to take part in organization of monkey's
      response to regular situations with the decision-making performed on the basis of
      existing experience. Other neurons became active in irregular situations
      involving no previous experience. The latter neurons seem to take part in other
      form of behaviour organization associated with creation of a new form of response
      to a new situation.

PMID- 7522775
TI  - [The spatial organization of the cortical afferent projections in the cat nucleus
      accumbens].

PMID- 7522777
TI  - [An experimental analysis of the development of local capillary stasis].
AB  - Micro-application of NaCl induced a local slowdown to full stoppage of the blood
      flow in the lamina of individual capillaries in the Wistar rats mesenterium. The
      blood stasis resulted from local disturbances of the blood rheological
      properties. The erythrocyte aggregates obstructed the capillaries leaving no
      space for the parietal plasma layer. The findings suggest the intravascular
      erythrocyte aggregation to be the immediate cause of the blood flow disturbances
      and the blood stasis in the microvascular lumina.

PMID- 7522778
TI  - [The distribution of the erythrocytes in the capillaries branching from a common
      precapillary arteriole].

PMID- 7522779
TI  - [The pattern-dependent mechanisms of the neural regulation of the microvascular
      tonus in the rat stomach].
AB  - The effects of electrical stimulation of the left splanchnic nerve in 1 s bursts
      at 4 s intervals at 5-80 Hz or continuously at 1-16 Hz (6 V, 1 ms) on gastric
      submucosal microvasculature were studied by the reflected light in vivo TV
      microscopy. Burst stimulation, like a continuous one, induced frequency-dependent
      vasoconstrictor responses. Maximal reduction in diameter of both arterioles (by
      about 90%) and venules (by about 60%) occurred at the same total number of
      stimuli delivered for 1-min period of nerve stimulation continuously at 16 Hz or
      in bursts at 80 Hz. In other frequencies used, burst stimulation evoked
      significantly more pronounced contractile responses of arterioles (but not the
      venules), which followed by much less pronounced autoregulatory escape and
      poststimulatory hyperemia as compared to continuous stimulation at the comparable
      total number of impulses. After alpha-adrenoreceptor blockade, reduced in
      magnitude and slow developing contractile responses of arterioles persisted to
      stimulation in bursts rather than continuously suggesting the involvement of
      nonadrenergic co-transmitters) release. The data obtained show that not only the
      number of neural pulses but also their bursting pattern may have an informational
      role in microvascular contractile responses. Bursting pattern of nerve
      stimulation seems to be more "physiological" than the continuous one.

PMID- 7522776
TI  - [The physiological problems of biofeedback control by the heart rate].
AB  - The data on voluntary regulation of the heart rate in humans is given in respect
      to individual-typological differences of adaptive abilities, ecological specifics
      of ambient environment and labour, health condition (neuroses, vegetative
      vascular dystonias etc.). A major role of training of the rhythmic regulatory
      processes for the biological feedback control, is corroborated.

PMID- 7522782
TI  - [Vladimir Aleksandrovich Govyrin].

PMID- 7522780
TI  - [Cerebral blood flow dynamics in monkeys breathing a helium-oxygen mixture under
      high pressure].
AB  - Breathing with normoxic helium-oxygen mixture under high pressure successively
      induced tremor, myoclonia, seizures. Blood flow and the pO2 during the motor
      disorders increased, depending in the pressure, in the cortex, caudate nucleus,
      black substance and reticular formation.

PMID- 7522781
TI  - [Combinations of methods for the monitoring of the cerebral microcirculation].
AB  - Any single method for measuring changes in local cerebral blood flow (LCBF) or
      blood vessels during physiological stimuli has individual strengths and
      deficiencies. The coupling of multiple methods based on different physical
      principles permits simultaneous measurements and tests of interrelated
      cerebrovascular changes and mechanisms. The present paper describes combined
      recordings of LCBF by H2 clearance with inhalation (H2Cl-Inh) and with steady
      electrochemical generation (H2Cl-Gen), by laser Doppler flowmetry (LDF) and by
      dimensional changes in surface vessels with videomicroscopy through acute cranial
      windows in rats anesthetized with urethane 1g/kg or urethane (0.6 g/kg) plus
      chloralose (0.05 g/kg)ip. For H2Cl-Gen recordings paired or quadred Pt sharped
      block of electrodes (diameter 0.04-0.06 mm) with distance between single
      electrode 0.3-0.5 mm, was inserted to brain tissue in barrel cortex. One
      electrode was used for H2 generation and others for LCBF recordings and their
      position in brain tissue was examined morphologically. Increase local blood flow
      in barrel cortex and arterial dilation were stimulated by inhalation of 7% CO2
      and mechanical stimulation of the contralateral whiskers. H2Cl-Inh was a "gold
      standard" for quantitative measurements of LCBF within a tissue radius 0.3-0.5 mm
      from the recording electrode during related tests during steady states at the
      same site. H2Cl-Gen was very sensitive to transient changes in flow and could
      record latencies. H2Cl-Gen was calibrated for quantitative measurements of
      changes in LCBF by pairing with H2Cl-Inh responses to CO2 inhalation. The laser
      Doppler miniature probe recorded the time course and normalized intensity changes
      within an approximate 1 mm3 volume of cortex but with more background noise and
      less sensitivity compared to H2Cl-Gen. Bright illumination of the cranial window
      increased LCBF by both methods in these experiments. The diameters of surface
      arterioles and venues were measured in single video frames with date-time markers
      for correlation with electrical recordings. Changes in diameter were small and
      were slower compared to H2Cl-Gen and LDF in the present recordings. Received data
      permit to conclude that there are two optimal combinations of methods were (1)
      H2Cl-Gen and H2Cl-Inh for both dynamic sensitivity and quantitative LCBF during
      systemic and neuronal stimulation, and (2) H2Cl-Gen, LDF, and videomicroscopy for
      multidimensional monitoring of cerebral circulation.

PMID- 7522783
TI  - [The role of the paraventricular hypothalamic nuclei in the development of
      chronic neurogenic hypertension and the formation of a self-stimulation
      reaction].
AB  - Effects of bilateral electric lesion of the hypothalamic paraventricular nuclei
      on cardiovascular components of the defense response and on the self-stimulation
      operant behaviour, were studied in rats. Overloading of the highest nervous
      activity induced no hypertension in these animals, though the self-stimulation
      frequency increased.

PMID- 7522784
TI  - [Emotional stress and extracardiac regulation].
AB  - Chronic experiments in rabbits and rats revealed that, when sympathetic
      influences on the heart prevail during emotional stress, reduce the heart
      electric stability, induce disorders in the heart rhythm and lead to arterial
      hypertension. Prevailing of parasympathetic influences, on the contrary, augments
      the heart electric stability, interferes with an increase in the catecholamines
      content and prevents structural lesions in the myocardium. Arterial hypertension
      is absent, at that. The vagal nerves seem to exert an adaptational-trophic and
      defensive effects on the heart in emotional stress.

PMID- 7522785
TI  - [The activity of the lymphatic vessels under conditions of experimental stress
      exposures].
AB  - Lymphangions were found to possess a considerable ability for temperature
      adaptation under modelled stressful effects on humans. The minute volume of
      lymphangions was found to linearly depend on the temperature of bathing solution
      within the range of 22-41 degrees C. Aspirin and other non-steroid analgetic
      agents were found to exert an obvious dose-dependent negative inotropic effect on
      electric potentials and contractile activity of a lymphangion. Clinical
      experimental assessment and physiological justification of action of a new
      perfusion solution: polyvisoline, was given.

PMID- 7522786
TI  - [The role of the endothelium in the local vascular reactions of the skeletal
      muscles].
AB  - Chemical de-endothelialization of the m. gastrocnemius' vessels nearly completely
      blocked the working, reactive and postelongation hyperemia as well as the
      hyperemia induced with augmentation of the amplitude of intra-vessel pressure
      pulses. Endothelium seems to take part in the above responses through effects
      upon the vessels' smooth muscles of a vasodilatory substance released or
      synthesized by the endothelial cells in the mechanical deformation.

PMID- 7522787
TI  - [The "non-actomyosin" component of vascular wall contraction].
AB  - The matrix of connective tissue was found to take part in generation of the
      mechanical strength in isolated strips of the v. cava posterior wall under the
      effect of increased temperature. The finding corroborates the concept of the
      actomyosin interaction. The vessel tissue response to temperature seems to be
      formed by three mechanisms, two of them being of a non-actomyosin nature.

PMID- 7522788
TI  - [The kinetics of the reaction of the portal vein of the liver in the rat to
      catecholamines and acetylcholine].
AB  - The portal vein was shown to possess two pools of alpha-adrenoreceptors and m
      cholinoreceptors, and one beta-adrenoreceptor pool, with functional
      interrelationships among them. Increase in the temperature of the incubation
      medium to 40.5 and 41.0 degrees C induced characteristic changes of adrenergic
      response which were reversed or considerably attenuated by specific agonists and
      antagonists. The role of changes in the conformational membrane induced by
      adrenotropic substances in modulating specific responses to neurotransmitters and
      their agonists, is discussed.

PMID- 7522789
TI  - [The mechanisms of the changes in coronary vascular resistance in anaphylactic
      shock].
AB  - Anaphylactic shock decreased the coronary perfusion pressure, systemic arterial
      pressure and cardiac output in anesthetised dogs. After combined inhibition of
      cyclo-oxygenase and lipoxygenase with linoleate-hydroxamic acid, the anaphylactic
      coronary constriction and morphological cardiac lesions were considerably
      diminished. Activation of the lipoxygenase pathway seems to play a major role in
      development of the coronary constriction in anaphylaxis.

PMID- 7522790
TI  - [The variability of the arterial pressure in waking normotensive rats].
AB  - Specifics of arterial pressure, interrelationships among the arterial pressure,
      heart rate and baroreceptor reflex, were studied in alert normotensive rats.
      Absence of any correlation between the middle level of arterial pressure and the
      latter's variability, was shown. No connections among the above parameters were
      found either.

PMID- 7522791
TI  - [The effect of glucocorticoid hormones on the blood pressure and contractile
      activity of the mesenteric arteries in rats].
AB  - Methylprednisolone (MP) induced first a decrease and then an increase of the
      blood pressure in Wistar rats. The hypertensive effect stabilised after three
      administrations. The contractile response amplitude in electric stimulation of
      the vascular-motor nerves first increased and then sharply dropped. The
      glycocorticoids were concluded to reduce the contractile properties of vessels
      simultaneously increasing the blood pressure.

PMID- 7522795
TI  - Nursing's newest unemployed.

PMID- 7522792
TI  - [The effect of the intraventricular administration of oxytocin on the functional
      activity of the epiphysis, adrenals and gonads and on the behavior of rats].
AB  - Intraventricular administration of oxytocin (OT) facilitated horizontal
      locomotion and inhibited their decrease in rats. OT also increased the number of
      face grooming responses but did not affect the genital grooming. The OT seems to
      suppress the pineal gland activity, whereas the plasma concentration of
      testosterone did not change and the corticosterone concentration increased. The
      OT seems to exert a complex effect on the nervous and endocrine systems.

PMID- 7522794
TI  - New International Organization for Standardization Technical Committee on
      application of ISO 9000 to medical devices.

PMID- 7522793
TI  - [The role of nitric oxide in the development of reactive hyperemia in the
      coronary bed].
AB  - De-endothelialization of the coronary vessels induced a 3-4-fold decrease in the
      level of hyperemia in anesthetised dogs. Infusion of L-arginine augmented the
      reactive hyperemia and the endothelium-dependent relaxation in response to
      acetylcholine administration. The reactive hyperemia seems to be wholly depending
      on the endothelium, being conditioned by the effect of endothelium-derived nitric
      oxide.

PMID- 7522796
TI  - A description of medical-surgical nursing.
AB  - The Iowa Nursing Intervention Classification research project asked the Academy
      of Medical Surgical Nurses to complete a survey, identifying which of 336
      interventions were used by this specialty and the frequency of their use. The
      results of this survey and potential implications for nursing practice are
      discussed.

PMID- 7522797
TI  - Mechanisms of myelin basic protein and proteolipid protein targeting in
      oligodendrocytes (review).
AB  - The segregation of proteins to specific cellular membranes is recognized as a
      common phenomenon. In oligodendrocytes of the central nervous system,
      localization of certain proteins to select regions of the plasma membrane gives
      rise to the myelin membrane. Whilst the fundamental structure and composition of
      myelin is well understood, less is known of the mechanisms by which the
      constituent proteins are specifically recruited to those regions of plasma
      membrane that are forming myelin. The two principal proteins of myelin, the
      myelin basic protein and proteolipid protein, differ greatly in character and
      sites of synthesis. The message for myelin basic protein is selectively
      translocated to the ends of the cell processes, where it is translated on free
      ribosomes and is incorporated directly into the membrane. Proteolipid protein
      synthesized at the rough endoplasmic reticulum, processed through the Golgi
      apparatus, and presumably transported via vesicles to the myelin membrane. This
      review examines the mechanisms by which these two proteins are targeted to the
      myelin membrane.

PMID- 7522798
TI  - Immune recognition of hormonogenic sites of human thyroglobulin: studies of
      Graves' sera and a murine monoclonal antibody with thyroid hormone antibody
      activity.
AB  - We synthesized four peptides (HTg-1, 1-10; HTg-2, 2547-2558; HTg-4, 2592-2603 and
      HTg-6, 2737-2748) and two peptides (HTg-3, 2582-2591 and HTg-5, 2687-2694) with
      or without hormonogenic acceptor tyrosine of human thyroglobulin (hTg). They were
      iodinated with 127I or 125I. 127I-labeled peptides were tested for their ability
      to displace 125I-T4 binding to thyroid hormone autoantibodies (THAA) in two cases
      of Graves' disease and to a murine anti-hTg monoclonal antibody with anti-T4
      activity (mAb). 125I-labeled peptides were tested for the direct binding to the
      aforementioned antibodies. None of the peptides displaced 125I-T4 binding to THAA
      or to a mAb, or exhibited increased binding to THAA and to a mAb. 125I-T4 binding
      to a mAb was equally displaced by hTgs obtained from a normal thyroid gland (NTg)
      and a case of Hurthle cell adenoma with undetectable iodine content (CTg). 125I
      T4 binding to serum gamma globulin in each patient's serum was completely
      displaced by NTg, but CTg displaced 125I-T4 binding 2% and 5% in Case 1 and Case
      2, respectively. It was speculated that the mAb recognizes a topological epitope
      around the hormonogenic site of hTg, while that of THAA in our two cases
      recognizes only T4 or an iodine dependent topological epitope(s) of hTg.

PMID- 7522800
TI  - Inhibition of steroid-induced prostatic hyperplasia in rats by treatment with
      anti-androgen (TZP-4238).
AB  - The effect of a synthetic steroidal anti-androgen, TZP-4238, on steroid-induced
      rat prostatic hyperplasia was investigated. Male Wistar rats were divided into
      four experimental groups. Group 1 consisted of intact controls. The other animals
      were castrated. The castrated animals were treated for 7 weeks with 1)
      testosterone 1 mg/head plus 17 beta-estradiol (E2) 0.01 mg/head (Group 2), 2)
      testosterone plus E2 + TZP-4238 8 mg/kg (Group 3) and 3) testosterone plus E2 +
      chlormadinone acetate (CMA) 20 mg/kg (Group 4). TZP-4238 and CMA were
      administered orally for 4 weeks after 3 weeks treatment with testosterone plus
      E2. In group 2, glandular hyperplasia of the prostate was clearly observed, and
      the number of bromo-deoxyuridine (BrdU)-positive cells showed a significant
      increase. In contrast, combined treatment with TZP-4238 (Group 3) or CMA (Group
      4) produced marked atrophy of the glandular epithelium, and the number of BrdU
      positive cells were remarkably decreased compared with Group 2. In addition, the
      localization of glutathione-peroxidase (GSH-PO) which effectively reduces the
      lipid peroxides in the glandular epithelial cells was markedly decreased.
      Furthermore, nuclear immunostaining of androgen receptor was remarkably decreased
      after combined treatment with TZP-4238 or CMA. Our data indicate that TZP-4238 is
      a potent steroidal androgen receptor antagonist for the prevention of rat
      prostatic growth in the steroid-induced prostatic hyperplasia model.

PMID- 7522801
TI  - [Inflammatory proteins of the seminal fluid].
AB  - If the clinical asymptomatic infection of the genital tract is a very frequent
      diagnosis of the hypofertility, it's quite important to know if the infection is
      evolutive or not. The assessment of inflammatory proteins of the seminal plasma
      as albumin IgA, gamma-globulins, lysozyme allows to do the differential
      diagnosis. So, an increase of such proteins is the expression of an evolutive
      infection.

PMID- 7522799
TI  - An inhibitory effect of TZP-4238 on the growth of androgen-sensitive rat
      prostatic tumor (Dunning R3327).
AB  - An inhibitory effect of TZP-4238, a newly synthesized antiandrogen, on the growth
      of Dunning R3327 rat prostatic tumor was studied and compared with that of
      chlormadinone acetate (CMA). TZP-4238 markedly suppressed the growth of R3327
      tumor. The inhibitory effect of TZP-4238 on the tumor was more potent than that
      on the prostate. While the inhibitory effect of TZP-4238 on the weight of the
      ventral prostate was about 6 times as great as that of CMA, the suppressive
      effect of TZP-4238 on tumor weight was about 40 times as great as that of CMA.
      Serum levels of testosterone and dihydrotestosterone showed no obvious changes
      after the administration of either TZP-4238 or CMA. The inhibitory effect of TZP
      4238 on the growth of R3327 tumor indicated the application of the compound to
      human prostatic cancer.

PMID- 7522803
TI  - The incidence of meningococcal illness in the East Anglian Regional Health
      Authority: 1990-1991.
AB  - The rate at which notifications of meningococcal meningitis were reported by
      districts of the East Anglian Regional Health Authority to the Office of
      Population Censuses and Surveys (OPCS) varied between 6.8 and 28.0 cases per
      million resident population per year between 1987 and 1991. A study was conducted
      to find out whether this variation represented differences in incidence,
      completeness of notification, or reporting practices. One hundred and one cases
      of meningococcal illness with onset between 1 January 1990 and 31 December 1991
      were identified retrospectively in residents of the East Anglian region
      (population 2.06 million). The ascertained incidence of meningococcal illness was
      24.5 cases/million/year with a range between districts of 13.1 to 35.7
      cases/million/year, similar to that expected from national data. Most of the
      variation in the rates of reporting to OPCS was explained by the practices of two
      consultants in communicable disease control (CCDCs), who reported all cases of
      which they were aware, irrespective of statutory notification. The study showed
      that communication to CCDCs was sometimes inadequate, and that control measures
      were not instituted in a small proportion of cases. The recommendations resulting
      from this study are, firstly, that OPCS should produce clear guidelines for
      notification and reporting. In the meantime proper officers should make their
      reporting practice explicit. Secondly, a sensitive case definition for
      meningococcal illness is needed for local monitoring of prophylactic coverage.
      Thirdly, CCDCs, microbiologists, clinicians, and environmental health officers
      should review arrangements for data exchange.

PMID- 7522804
TI  - Viral gastroenteritis associated with a sandwich bar.

PMID- 7522805
TI  - Surveillance of waterborne disease in England and Wales.
AB  - A pilot scheme, designed to improve the information on waterborne disease
      available nationally, was set up in five health regions from October 1991 to
      March 1992. Consultants in communicable disease control were asked to report each
      month on confirmed and suspected cases of waterborne disease, and microbiological
      and other contamination incidents. Twelve events were reported to the PHLS
      Communicable Disease Surveillance Centre (CDSC) in six months: five involved
      human illness and seven were contamination incidents. Six other events were
      reported to CDSC from regions that did not take part in the scheme. The total
      number of events reported was small and epidemiological evidence that linked
      disease with water consumption was often weak or absent. Nevertheless, the scheme
      provided valuable information on events associated with water and would prove
      useful if it were established nationally, linked with guidance on the
      investigation of incidents.

PMID- 7522802
TI  - Acidification of extracellular environment inhibits CCK-8-induced Ca2+ entry into
      pancreatic acinar cells of rat evaluated by a Mn(2+)-quenching method.
AB  - The fluorescence of fura 2, a Ca(2+)-sensitive dye, is quenched in the presence
      of other divalent cations such as Mn2+. This characteristic of the dye provides a
      useful measure for investigating the role of Ca2+ in cellular functions. The
      present experiments were thus designed to examine the effects of extracellular pH
      (pHo) on cholecystokinin octapeptide (CCK-8)-induced Ca2+ entry into isolated
      perifused pancreatic acini of the rat using a Mn(2+)-quenching method. At a
      standard pHo (7.4), addition of Mn2+ (1 mM) during continuous stimulation with
      100 pM CCK-8 quenched fura 2 fluorescence excited by both excitation wavelengths
      of 340 and 380 nm. Lowering pHo to 6.0 weakened the quenching, whereas elevating
      pHo to 8.0 during the stimulation accelerated the quenching compared with that at
      standard pHo. Accordingly, when acinar cells were stimulated continuously with
      100 pM CCK-8 at pHo 6.0, the second sustained increase in cytosolic Ca2+
      concentration ([Ca2+]i) was decreased compared with that at pHo 7.4, but the
      [Ca2+]i increase reappeared when the pHo was neutralized from 6.0 to 7.4 even
      after cessation of the stimulation. The second sustained increase of [Ca2+]i was
      achieved at pHo 8.0, but it declined rapidly when CCK-8 stimulation was
      terminated and pHo was simultaneously restored to 7.4. Amylase release induced by
      continuous stimulation with 100 pM CCK-8 showed a biphasic time course. A second
      sustained phase of amylase release was significantly reduced at pHo 6.0, but
      amylase release increased again when pHo was restored to 7.4. These results
      indicate that extracellular pH modifies the extent of secretagogue-induced Ca2+
      entry into the pancreatic acinar cell, and the inhibitory effects of lowered pHo
      on the secretory response are largely due to a limited increase in [Ca2+]i.

PMID- 7522806
TI  - Epidemiology of meningococcal disease and a community outbreak in Somerset.
AB  - We describe the epidemiology of meningococcal disease in Somerset and a community
      outbreak in one district. Fifty-seven cases of meningococcal disease occurred in
      residents of Somerset between 1 May 1990 and 30 April 1993 (incidence
      4.7/100,000/year), of whom six died. Thirteen of the cases occurred in one local
      authority area in a six month period from 1 November 1992 to 30 April 1993; an
      incidence of 26.6/100,000/year. Twenty-seven patients were given benzyl
      penicillin before admission to hospital. General practitioners were significantly
      more likely to give benzylpenicillin to patients with rashes. The proportion that
      received prophylaxis tended to increase after a press release was issued and
      general practitioners were advised. The number of cases was too small to
      demonstrate the protective effect of early administration of benzylpenicillin. In
      five cases the consultant in communicable disease control was not informed for
      over 12 hours. Thirty-seven of the 48 index cases for whom information was
      available received rifampicin prophylaxis before discharge from hospital.

PMID- 7522808
TI  - Serological surveillance in The Netherlands.

PMID- 7522807
TI  - Age specific antibody prevalence to parvovirus B19: how many women are infected
      in pregnancy?
AB  - Infection with parvovirus B19 is an important cause of late fetal mortality in
      the second trimester, and many infections in pregnancy remain undiagnosed. A
      serological survey stratified by age has been used to estimate the incidence of
      maternal infection with parvovirus B19 in pregnancy. Serum remaining from
      specimens submitted for diagnosis from 6864 people of all ages to seven public
      health laboratories in England was tested for antibody to parvovirus B19. The
      antibody prevalence rose with age to 45% at 10 years and 60% to 70% in adults.
      The age specific force of infection was highest in children aged less than 10
      years and lowest in adults. Maternal infection with parvovirus B19 is estimated
      to occur in approximately one pregnancy in 400. It has been estimated that fetal
      death occurs in 9% of these cases, which suggests that parvovirus B19 may cause
      more than 150 fetal deaths in England and Wales each year. Testing for evidence
      of recent infection with parvovirus B19 should be considered for unexplained
      cases of fetal hydrops in the second trimester, especially in years of parvovirus
      B19 epidemics.

PMID- 7522810
TI  - Invasive group A streptococcal infections--update.

PMID- 7522809
TI  - Meningococcal infections in England and Wales: 1993.
AB  - One thousand two hundred and ninety-seven meningococcal isolates of clinical
      significance were submitted for examination to the PHLS Meningococcal Reference
      Unit in 1993; almost the same total as in 1992. Changes in the number of isolates
      from individual regions ranged from falls of 25% to increases of 42%. The
      incidence of meningococcal disease rose late in 1993, apparently affected by the
      epidemic of influenza. The number of statutory notifications reported to the
      Office of Population Censuses and Surveys was--for the first time--markedly
      higher than the number of laboratory diagnosed cases. Serodiagnosis was used to
      confirm an increased number of clinically suspected cases in 1993.

PMID- 7522811
TI  - Strategies to reduce vertical transmission of HIV-1.

PMID- 7522813
TI  - Immunisation against influenza.

PMID- 7522812
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7522815
TI  - Legionnaires' disease in the West Midlands.

PMID- 7522818
TI  - Adverse reaction to smallpox vaccine.

PMID- 7522816
TI  - Malaria acquired in temperate zones.

PMID- 7522819
TI  - The control of infection acquired in hospital: a national study.

PMID- 7522817
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7522814
TI  - National measles and rubella immunisation campaign.

PMID- 7522820
TI  - Salmonella infections, England and Wales: reports to the PHLS (Salmonella data
      set).

PMID- 7522822
TI  - Surveillance of waterborne disease in England and Wales.

PMID- 7522823
TI  - Arenavirus infection acquired in the laboratory.

PMID- 7522824
TI  - Surveillance of overwhelming infection following splenectomy.

PMID- 7522821
TI  - An outbreak of Salmonella paratyphi B in France.

PMID- 7522826
TI  - New diagnostic tests of GH reserve.
AB  - Pharmacological tests are essential for the diagnosis of growth hormone (GH)
      insufficiency. Obesity is a pathological state associated with blunted GH
      response to all the classical stimuli tested. In the present study, three new
      pharmacological stimuli for GH reserve were evaluated in three groups of
      subjects: Normal, GH-insufficient and normal growing obese children.
      Dexamethasone provokes a clear GH-response in normal children, whereas the
      response in the other 2 groups of patients is significantly diminished. Galanin
      induced GH-secretion is significantly higher in normal than in obese children.
      GHRP-6 causes a potent GH release in normal children, higher than in GH
      insufficiency or obesity. The overlap shown between GH-insufficient patients and
      normal children reduces the usefulness of the tests. Similar to the classical
      stimuli, the response to these new tests is also decreased in obesity.

PMID- 7522829
TI  - Temperature gradient gel electrophoresis (TGGE) for the detection of polymorphic
      DNA and RNA.

PMID- 7522825
TI  - Neurotransmitter control of growth hormone secretion in humans.
AB  - Growth hormone secretion is mainly regulated by the interplay of GHRH and
      somatostatin, two specific hypophysiotrophic neurohormones. In addition to GHRH
      and somatostatin, many neurotransmitters and neuropeptides influence GH secretion
      mainly by acting at the hypothalamic level. This paper focuses on the stimulatory
      role of acetylcholine, arginine and galanin as well as on the inhibitory
      influence of catecholamines which is mediated by the activation of beta
      adrenergic receptors. Attention will be given to the age-related changes in the
      neural control of GH secretion from childhood to old age.

PMID- 7522828
TI  - Analysis of DNA restriction enzyme digests by two-dimensional electrophoresis in
      agarose gels.

PMID- 7522830
TI  - TGGE in quantitative PCR of DNA and RNA.

PMID- 7522827
TI  - The simultaneous isolation of RNA and DNA from tissues and cultured cells.

PMID- 7522831
TI  - Single primer-mediated polymerase chain reaction.

PMID- 7522833
TI  - Hepatitis C (HCV)-positive blood donors in south-west England: a case control
      study.
AB  - The aim of this study was to compare the socio-demographic characteristics and
      risk factors in anti-HCV positive blood donors with those of matched controls.
      The participants were 50 hepatitis C antibody (HCV) positive blood donors and 50
      matched blood donors with no evidence of HCV infection, who gave blood to the
      South Western Transfusion Centre between November 1991 and July 1992. A
      confidential structured interview was conducted to collect socio-demographic data
      and to elicit information on risk factors for HCV. Measurements were made of the
      prevalence of risk factors and socio-demographic characteristics in cases and
      controls. The main results were that 45 of the 50 cases could have been exposed
      to HCV by previous intravenous drug abuse (IVDA), blood transfusion or medical
      employment. Cases were significantly more likely to have a history of IVDA,
      tattooing or of medical employment than matched controls. Cases with no history
      of IVDA were significantly more likely to have had a blood transfusion. The key
      conclusions to emerge are that current policies are ineffective at excluding
      those with a history of IVDA from the donor pool. Consideration should be given
      to the introduction of a policy of direct confidential questioning about risk
      factors for all donors, or, at a minimum, the use of a questionnaire.

PMID- 7522832
TI  - Coral-host specificity of Red Sea Lithophaga bivalves: interspecific and
      intraspecific variation in 12S mitochondrial ribosomal RNA.
AB  - Comparison of 12S mitochondrial ribosomal DNA sequences was used to approach the
      question of species specificity between boring bivalves of the genus Lithophaga
      and their coral hosts. A 450-bp long fragment was amplified by PCR from 13
      individuals belonging to five subgroups of Lithophaga bivalves. These subgroups
      are defined according to their coral hosts species, and they belong to three
      currently recognized species: L. lessepsiana (1 host), L. simplex (2 hosts), and
      L. purpurea (2 hosts). All bivalves were collected from corals growing within an
      approximately 200-m section of the reef of Eilat, Red Sea. Sequence variation
      between members of the same species inhabiting different hosts (30-32%) was found
      to be very similar to the variation exhibited between recognized species. These
      results, when interpreted together with previously published data concerning
      variations among Lithophaga subgroups, support the notion of a very high degree
      of species specificity between Lithophaga bivalves and their coral hosts in the
      Red Sea.

PMID- 7522834
TI  - A study of anti-hepatitis C positive blood donors: the first year of screening.
AB  - In the U.K., blood donations have been routinely screened for anti-HCV since
      September 1991. In order to get the most epidemiological benefit from these
      extensive screening data, the histories obtained at counselling from donors
      confirmed to be anti-HCV positive, 'indeterminate' and falsely positive have been
      analysed in detail. In addition, the associations with potential risk factors
      have been investigated by comparing these groups of donors with a control group
      of 771 routine donors bled on one day during the study, at North London Blood
      Transfusion Centre. This paper documents the prevalence and demography of HCV
      infection in asymptomatic blood donors, to assess various possible sources of
      infection and the association between liver function test results and alcohol
      consumption in donors. One in 1400 previously untested donors was confirmed
      positive for anti-HCV. Age (the group 30-49 years being highest), tattooing and
      intravenous drug use in both sexes, ear-piercing in males and blood transfusion
      in females were all significantly associated with an increased risk of HCV
      infection. Intravenous drug use proved to be the factor most strongly associated
      with risk. Liver function tests (alanine aminotransferase) were elevated in a
      significant number of donors confirmed to be anti-HCV positive but no clear
      correlation between alanine aminotransferase level and either time since
      infection or alcohol consumption was found. Alcohol consumption was significantly
      higher in donors confirmed to be anti-HCV positive and was particularly marked in
      those admitting to previous intravenous drug use.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7522835
TI  - Supplemental HCV antibody assay in blood donors by RIBA and line immunoassay.

PMID- 7522837
TI  - Epidermal growth factor-induced mitogen signals in cultured intestinal epithelial
      cells.
AB  - Epidermal growth factor (EGF) stimulated proliferation of an intestinal cell line
      (IEC-6 cells), derived from rat jejunal crypts. EGF-induced tyrosine
      phosphorylation was analyzed by immunoblotting with a monoclonal antibody
      specific for phosphotyrosine. EGF initiated rapid tyrosine phosphorylation of
      proteins with molecular masses of 185, 170, 55, and 42 kilodalton (kDa). In
      addition, EGF caused the rapid elevation of intracellular free Ca2+
      concentration. Thus, EGF-stimulated proliferation and its mitogen signals were
      clearly observed in IEC-6 cells, suggesting that EGF may play an important role
      in the maintenance and repair of the intestinal mucosa in vivo.

PMID- 7522839
TI  - Transient iron-overload with bleomycin-detectable iron present during
      cardiopulmonary bypass surgery.
AB  - Extracorporeal circulation of blood during cardiopulmonary bypass surgery exposes
      cells to non-physiological surfaces and shear stress which can activate several
      regulatory cascades, and neutrophils to release superoxide and hydrogen peroxide.
      Shear stresses generated by pumps and suction systems cause lysis of red blood
      cells and the release of haemoglobin. Together the release of reactive forms of
      oxygen and haemoglobin can lead to the appearance of low molecular mass
      chelatable iron (bleomycin-detectable iron). All patients undergoing open heart
      surgery appear to release iron to plasma transferrin, increasing its iron
      saturation. In 13% of patients, however, the transferrin became fully iron
      saturated, and by the end of open-heart surgery we could detect bleomycin
      chelatable iron in the plasma. Saturation of transferrin with iron eliminates its
      iron-binding antioxidant properties, which can result in a stimulation of iron
      dependent radical damage to selected detector molecules.

PMID- 7522836
TI  - Control mechanisms of liver regeneration.

PMID- 7522840
TI  - High-performance liquid chromatography and photoaffinity crosslinking to explore
      the binding environment of nevirapine to reverse transcriptase of human
      immunodeficiency virus.
AB  - Nevirapine (BI-RG-587) is a potent inhibitor of the polymerase activity of
      reverse transcriptase of human immunodeficiency virus type-1. Nevirapine, as well
      as several other non-nucleoside compounds of various structural classes, bind
      strongly at a site which includes tyrosines 181 and 188 of the p66 subunit of
      reverse transcriptase. The chromatography which was utilized to explore this
      binding site is described. BI-RH-448 and BI-RJ-70, two tritiated photoaffinity
      azido analogues of nevirapine, are each crosslinked to reverse transcriptase. The
      use of several HPLC-based techniques employing different modes of detection makes
      it possible to demonstrate a dramatic difference between the two azido analogues
      in crosslinking behavior. In particular, by comparing HPLC tryptic peptide maps
      of the photoadducts formed between reverse transcriptase and each azido analogue,
      it can be shown that crosslinking with BI-RJ-70 but not with BI-RH-448 is more
      localized, stable, and hence exploitable for the identification of the
      specifically bonded amino acid residue(s). In addition, comparison of the tryptic
      maps also makes it feasible to assess which rings of the nevirapine structure are
      proximal or distal to amino acid side chains of reverse transcriptase. Finally,
      another feature of the HPLC peptide maps is the application of on-line detection
      by second order derivative UV absorbance spectroscopy to identify the crosslinked
      amino acid residue.

PMID- 7522841
TI  - Immobilized metal-ion affinity partitioning of NAD(+)-dependent dehydrogenases in
      poly(ethylene glycol)-dextran two-phase systems.
AB  - Affinity partitioning of yeast alcohol dehydrogenase (YADH), lactate
      dehydrogenase from rabbit muscle (MLDH) and lactate and malate dehydrogenases
      from pig heart (HLDH and HMDH, respectively) were studied in aqueous two-phase
      systems containing metal ions (Cu2+, Ni2+, Zn2+ and Cd2+) chelated by
      iminodiacetate-poly(ethylene glycol) (IDA-PEG). The partitioning behaviour of the
      enzymes in the presence of Cu(II)-IDA-PEG was studied as a function of the
      concentration of NaCl, the pH of the medium and the concentration of added
      selected agents. It was demonstrated that the partition effect (delta log K) of
      dehydrogenases in the presence of Cu(II)-IDA-PEG and the affinity of enzymes for
      immobilized Cu2+ ions increases in the order MLDH > YADH > HMDH > or = HLDH. It
      was shown that the determined variations in the enzyme affinities for Cu(II)-IDA
      PEG might be related to the differences in the content of histidine residues
      accessible to the solvent.

PMID- 7522838
TI  - Esophageal endoprosthesis in malignant stricture.

PMID- 7522842
TI  - Effect of tumor necrosis factor-alpha on the expression of insulin-like growth
      factor I and insulin-like growth factor binding protein 4 in mouse osteoblasts.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine produced by immune cells,
      which has multiple effects on bone cells and is therefore thought to mediate
      changes in bone metabolism occurring during inflammation. In the present study we
      have investigated the effect of TNF-alpha on the secretion of insulin-like growth
      factor I (IGF-I) and IGF binding protein 4 (IGFBP-4) by clonal mouse osteoblasts
      (MC3T3-E1 cells) using subconfluent in vitro cultures and serum-free conditions.
      The IGF-I was determined by radioimmunoassay under conditions eliminating the
      interference of IGFBPs. Treatment of MC3T3-E1 cultures with TNF-alpha for 24 h
      resulted in a dose-dependent decrease in IGF-I secretion (maximally to 34 +/-
      9.7% of control with 60 pmol/l TNF-alpha; mean +/- SD). The TNF-alpha treatment
      also resulted in decreased messenger ribonucleic acid (mRNA) levels of IGF-I at 4
      and 24 h, as detected by Northern analysis. Because basal secretion of IGFBPs is
      very low in MC3T3-E1 cells, effects of TNF-alpha on IGFBP secretion were studied
      in cultures in which IGFBP-4 expression was increased by calcitriol (1,25(OH)2D3)
      treatment. The presence of TNF-alpha (600 pmol/l) inhibited this calcitriol
      induced stimulation of IGFBP-4 mRNA levels from 4 h onwards, with complete
      inhibition of the calcitriol effect occurring at 24 h. We also observed a dose
      dependent inhibition of calcitriol-stimulated IGFBP-4 secretion into the culture
      medium (as detected by Western ligand blot), with the maximal inhibition
      occurring with 600 pmol/l TFN-alpha to 25 +/- 7% of control levels.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7522843
TI  - Circulating insulin-like growth factor II/mannose-6-phosphate receptor and
      insulin-like growth factor binding proteins in fetal sheep plasma are regulated
      by glucose and insulin.
AB  - We have reported previously that levels of insulin-like growth factor I (IGF-I)
      and IGF-II in fetal sheep plasma decrease with maternal starvation and increase
      following an infusion of glucose to the starved fetus, while a fetal infusion of
      insulin elevates UGF-I alone. We now report the changes in the circulating IGF
      II/M6P receptor and plasma IGF binding proteins (IGFBPs), as measured by western
      blotting and ligand blotting, respectively, in fetus and mother during this
      study. In fetal plasma, the circulating IGF-II/mannose-6-phosphate (M6P)
      receptor, IGFBP-3 and IGFBP-4 were reduced during starvation. While circulating
      IGF-II/M6P receptor and IGFBP-4 levels were increased following the fetal insulin
      or glucose infusion, IGFBP-3 was unchanged and increased only after 48 h of
      maternal refeeding. Both IGFBP-1 and IGFBP-2 increased with starvation but while
      IGFBP-1 levels returned to control values following both insulin and glucose
      infusion, levels of IGFBP-2 were not reduced significantly by either infusion or
      by refeeding. In maternal plasma, levels of IGFBP-3 and IGFBP-4 decreased while
      IGFBP-1 and IGFBP-2 increased after 48 h of starvation. Levels of each IGFBP were
      unaltered following the fetal infusions but returned to values obtained during
      the control period after refeeding. These data show that each of the IGF carrier
      proteins is sensitive of changes in nutrition, either acutely, such as IGFBP-1,
      or chronically, as for IGFBP-3. This suggests that the circulating IGF-II/M6P
      receptor and the IGFBP's may modulate IGF activity in the fetus during different
      nutritional states.

PMID- 7522844
TI  - Nucleotide sequence, expression and transcriptional analysis of the
      Corynebacterium glutamicum gltA gene encoding citrate synthase.
AB  - Citrate synthase catalyses the initial reaction of the citric acid cycle and can
      therefore be considered as the rate-controlling enzyme for the entry of
      substrates into the cycle. In Corynebacterium glutamicum, the specific activity
      of citrate synthase was found to be independent of the growth substrate and of
      the growth phase. The enzyme was not affected by NADH or 2-oxoglutarate and was
      only weakly inhibited by ATP (apparent Ki = 10 mM). These results suggest that in
      C. glutamicum neither the formation nor the activity of citrate synthase is
      subject to significant regulation. The citrate synthase gene, gltA, was isolated,
      subcloned on plasmid pJC1 and introduced into C. glutamicum. Relative to the wild
      type the recombinant strains showed six- to eightfold higher specific citrate
      synthase activity. The nucleotide sequence of a 3007 bp DNA fragment containing
      the gltA gene and its flanking regions was determined. The predicted gltA gene
      product consists of 437 amino acids (M(r) 48,936) and shows up to 49.7% identity
      with citrate synthase polypeptides from other organisms. Inactivation of the
      chromosomal gltA gene by gene-directed mutagenesis led to absence of detectable
      citrate synthase activity and to citrate (or glutamate) auxotrophy, indicating
      that only one citrate synthase is present in C. glutamicum. Transcriptional
      analysis by Northern (RNA) hybridization and primer extension experiments
      revealed that the gltA gene is monocistronic (1.45 kb mRNA) and that its
      transcription initiates at two consecutive G residues located 121 and 120 bp
      upstream of the translational start.

PMID- 7522845
TI  - Mycobacterium leprae isolates from different sources have identical sequences of
      the spacer region between the 16S and 23S ribosomal RNA genes.
AB  - To test for genotypic variations between different isolates of Mycobacterium
      leprae, the causative agent of leprosy, the 282 bp spacer region between the 16S
      and 23S rRNA genes was amplified using PCR, and submitted to single-strand
      conformation polymorphism (SSCP) analysis. The procedure was optimized using four
      modified spacer fragments, containing mutations at one, three, four and six
      positions, respectively. Seventy-five M. leprae isolates from different sources,
      including isolates from leprosy patients, healthy individuals, armadillos and
      mouse footpads were identical in the SSCP analysis. DNA sequencing and
      restriction enzyme analysis performed on four and 40 samples, respectively,
      confirmed the results obtained with SSCP analysis.

PMID- 7522846
TI  - Immunoreactivity of the 60 kDa cysteine-rich proteins of Chlamydia trachomatis,
      Chlamydia psittaci and Chlamydia pneumoniae expressed in Escherichia coli.
AB  - The 60 kDa cysteine-rich proteins (CrPs) of Chlamydia are developmentally
      regulated outer envelope proteins synthesized late in the chlamydial growth
      cycle. These proteins, found only on the extracellular infectious elementary
      bodies, elicit major antibody responses in chlamydial infection. We have cloned
      and expressed in Escherichia coli the complete 60 kDa CrP genes from Chlamydia
      trachomatis, C. psittaci and C. pneumoniae. The recombinant products were
      expressed as either 'native' proteins or as fusions with the bacteriophage T7
      gene 10 protein. Electron microscopy showed that recombinant proteins were
      produced as insoluble inclusions within the E. coli host cells. The recombinant
      60 kDa CrPs were purified and used to raise high titre polyclonal antisera. In
      immunoblot analysis these antisera reacted with the 60 kDa CrPs from purified
      elementary bodies of all three chlamydial species in a genus-specific manner.
      Further molecular analysis allowed the genus-specific cross-reacting epitopes to
      be localized by using overlapping synthetic peptides covering the C. trachomatis
      60 kDa CrP. Immunogold labelling experiments, using purified infectious
      elementary bodies from the three chlamydial species indicated that the 60 kDa
      CrPs are not surface accessible to antibody binding.

PMID- 7522847
TI  - Monoclonal antibodies for Streptomyces lividans and their use for immunomagnetic
      capture of spores from soil.
AB  - Monoclonal antibodies were produced to Streptomyces lividans spore surface
      antigens. One particular hybridoma cell line, 43H6, produced a monoclonal
      antibody that reacted exclusively with Streptomyces cluster group 21 in an enzyme
      linked immunosorbent assay (ELISA). Antibody 43H6 was found to be of subclass
      IgG1, kappa light chain. Western blot (immunoblot) analysis revealed that 43H6
      recognized a major outer spore polypeptide of about 37,000 Da. The epitope was
      stably maintained in S. lividans spores over at least seven sporulation cycles on
      laboratory medium and for at least 14 weeks in sterile soil systems. The species
      group specificity of antibody 43H6 was exploited in the development of an
      immunocapture technique for the isolation of streptomycetes from soil. Magnetic
      beads coated with antibody 43H6 were mixed with soil samples seeded with S.
      lividans spores. Spore-bead complexes were recovered using magnets. Treatment of
      beads with blocking agents and the inclusion of detergents in the recovery system
      lessened non-specific binding of spores to beads and improved recovery. In buffer
      solutions decreasing the spore concentration increased the recovery values for a
      fixed bead concentration. At a spore concentration of 5 x 10(7) ml-1 the recovery
      was 4.3% whilst at 5 x 10(2) ml-1 it was 76% for a fixed bead concentration of
      0.6 mg ml-1. Using a bead concentration of 2 mg per 10 g soil, approximately 30%
      of the target spore population of 10(6) c.f.u. was recovered from sterile soil
      and 4% from non-sterile soil. This method offers a rapid means of selectively
      recovering and concentrating Streptomyces spores from soil samples.

PMID- 7522849
TI  - [Screening tests of anti-HVC antibodies used in France. Analysis of sensitivity].
AB  - The results concerning the hepatitis C antibodies screening tests sensitivity are
      presented by Viral Hepatitis Study Group of the French Society of Blood
      Transfusion. This evaluation was carried out in 1993, with five tests available
      for Hepatitis C Viral (HCV) antibodies screening. Several panels of human blood
      samples, collected by members of Viral Hepatitis Study Group, were used. For
      those specimens the data about whole serology (various reactivities against viral
      antigens) clinical history and other explorations (molecular biology, liver
      histology, other viral infections) are described. If possible all those results
      are used to describe some interpretation criteria for the HCV serology and
      sensitivity obtained for each screening test.

PMID- 7522851
TI  - Improving results of pediatric renal transplantation.
AB  - BACKGROUND: Outcome after renal transplantation in children has been variable. We
      undertook a retrospective study of our experience over the past five years. STUDY
      DESIGN: From January 1, 1988, to October 15, 1992, 60 renal transplantations were
      performed upon 59 children at the Children's Hospital of Pittsburgh. Twenty-eight
      (47 percent) of the kidneys were from cadaveric donors, and 32 (53 percent) were
      from living donors. The recipients ranged in age from 0.8 to 17.4 years, with a
      mean of 9.8 +/- 4.8 years. Forty-six (77 percent) recipients were undergoing a
      first transplant, while 14 (23 percent) received a second or third transplant.
      Eight (13 percent) of the patients were sensitized, with a panel reactive
      antibody of more than 40 percent. Eleven of the 14 patients undergoing
      retransplantation and seven of the eight patients who were sensitized received
      kidneys from cadaveric donors. Thirty-three (55 percent) patients received
      cyclosporine-based immunosuppression, and 27 (45 percent) received FK506 as the
      primary immunosuppressive agent. RESULTS: The median follow-up period was 36
      months, with a range of six to 63 months. The one- and four-year actuarial
      patient survival rate was 100 and 98 percent. The one- and four-year actuarial
      graft survival rate was 98 and 83 percent. For living donor recipients, the one-
      and four-year actuarial patient survival rate was 100 and 100 percent; for
      cadaveric recipients, it was 100 and 96 percent. Corresponding one- and four-year
      actuarial graft survival rates were 100 and 95 percent for the living donor
      recipients and 96 and 69 percent for the cadaveric recipients. Patients on
      cyclosporine had a one- and four-year patient survival rate of 100 and 97
      percent, and patients on FK506 had a one- and three-year patient survival rate of
      100 and 100 percent. Corresponding one- and four-year actuarial graft survival
      rates were 100 and 85 percent in the cyclosporine group, while one- and three
      year actuarial graft survival rates were 96 and 84 percent in the FK506 group.
      The mean serum creatinine level was 1.24 +/- 0.64 mg per dL; the blood urea
      nitrogen level was 26 +/- 13 mg per dL. The incidence of rejection was 47
      percent; 75 percent of the rejections were steroid-responsive. The incidence of
      cytomegalovirus was 10 percent. The incidence of post-transplant
      lymphoproliferative disorder was 8 percent. None of the patients on cyclosporine
      were able to be taken off prednisone; 56 percent of the patients receiving FK506
      were taken off prednisone successfully. Early growth and development data suggest
      that the patients receiving FK506 off prednisone had significant gains in growth.
      CONCLUSIONS: These results support the idea that renal transplantation is a
      successful therapy for end-stage renal disease in children. They also illustrate
      the potential benefits of a new immunosuppressive agent, FK506.

PMID- 7522852
TI  - Expression of growth associated protein 43 and neural cell adhesion molecule in
      congenital fibre type disproportion with interstitial myositis.
AB  - We report on the expression of growth associated protein (GAP)43 and neural cell
      adhesion molecule (NCAM) in congenital fibre type disproportion (CFTD) with
      myopathological additional signs of interstitial myositis. We assume that
      sarcolemmal GAP43 in developmental disordered myocytes plays a role in
      maintenance of growth morphology. In muscular dystrophy light microscopical
      evaluation reveals no GAP43 immunoreactivity in regenerating fibres. The
      expression of GAP43 seems to be a characteristic feature of CFTD. The expression
      of NCAM, particularly in the sarcolemma of small muscle fibres of CFTD, indicates
      a functional state of permanent partial denervation. Whether the steroid
      responsive interstitial myositis is pathogenetically related to CFTD or a
      coincidental inflammation is not known. Because of the clinical and
      myopathological data the differential diagnosis of Emery-Dreifuss muscular
      dystrophy is considered.

PMID- 7522854
TI  - Antigen-specific stimulation of histamine releasing factors in diisocyanate
      induced occupational asthma.
AB  - Diisocyanate-induced asthma differs from occupational asthma (OA) caused by
      protein allergens in that specific IgE antibody responses are rarely identified.
      To investigate the immunopathogenesis of diisocyanate asthma, diisocyanate
      exposed workers were evaluated for in vitro production of antigen-specific
      mononuclear cell-derived histamine releasing factor (HRF). The mean HRF response
      to diisocyanate-HSA antigens was significantly greater in patients with OA than
      in diisocyanate-exposed asymptomatic subjects (p < 0.05). No association was
      found between HRF and diisocyanate-specific antibodies. Analysis of HRF
      production by subpopulations of peripheral blood mononuclear cells (PBMC) showed
      that lymphocytes and adherent cells were major sources of both spontaneous and
      antigen-stimulated HRF. The results suggest that antigen-specific HRF produced by
      PBMCs are an important biomarker for diisocyanate-induced asthma. This is the
      first report of hapten-specific stimulation of PBMCs resulting in HRF production.

PMID- 7522850
TI  - Three years clinical experience with intestinal transplantation.
AB  - BACKGROUND: After the successful evolution of hepatic transplantation during the
      last decade, small bowel and multivisceral transplantation remains the sole
      elusive achievement for the next era of transplant surgeons. Until recently, and
      for the last thirty years, the results of the sporadic attempts of intestinal
      transplantation worldwide were discouraging because of unsatisfactory graft and
      patient survival. The experimental and clinical demonstration of the superior
      therapeutic efficacy of FK 506, a new immunosuppressive drug, ushered in the
      current era of small bowel and multivisceral transplantation with initial
      promising results. STUDY DESIGN: Forty-three consecutive patients with short
      bowel syndrome, intestinal insufficiency, or malignant tumors with or without
      associated liver disease, were given intestinal (n = 15), hepatic and intestinal
      (n = 21), or multivisceral allografts that contained four or more organs (n = 7).
      Treatment was with FK 506 based immunosuppression. The ascending and right
      transverse colon were included with the small intestine in 13 of the 43 grafts,
      almost evenly distributed between the three groups. RESULTS: After six to 39
      months, 30 of the 43 patients are alive, 29 bearing grafts. The most rapid
      convalescence and resumption of diet, as well as the highest three month patient
      survival (100 percent) and graft survival (88 percent) were with the isolated
      intestinal procedure. However, this advantage was slowly eroded during the first
      two postoperative years, in part because the isolated intestine was more prone to
      rejection. By the end of this time, the best survival rate (86 percent) was with
      the multivisceral procedure. With all three operations, most of the patients were
      able to resume diet and discontinue parenteral alimentation, and in the best
      instances, the quality of life approached normal. However, the surveillance and
      intensity of care required for these patients for the first year, and in most
      instances thereafter, was very high, being far more than required for patients
      having transplants of the liver, kidney or heart. CONCLUSIONS: Although
      intestinal transplantation has gone through the feasibility phase, strategies
      will be required to increase its practicality. One possibility is to combine
      intestinal transplantation with contemporaneous autologous bone marrow
      transplantation.

PMID- 7522848
TI  - Evolutionary affiliation of the marine nitrogen-fixing cyanobacterium
      Trichodesmium sp. strain NIBB 1067, derived by 16S ribosomal RNA sequence
      analysis.
AB  - The 16S rRNA sequence of Trichodesmium sp. strain NIBB 1067 was determined and
      used for the construction of a distance tree and bootstrap analysis. The tree
      shows that, among the available cyanobacterial 16S rRNA sequences, Trichodesmium
      NIBB 1067 has Oscillatoria PCC 7515 as its closest relative, presenting 94.9% of
      sequence similarity with the latter strain. This is in contrast to a difference
      of 9 mol% G+C in mean genomic DNA base composition between the two organisms.
      Nevertheless, the genotypic heterogeneity presented by a number of strains
      assigned to the genus Oscillatoria hinders a taxonomic decision on the separate
      existence of the genera Trichodesmium and Oscillatoria. The sequence of the
      internal transcribed spacer (ITS) between the 16S and 23S rRNA genes was also
      determined, as a possible marker to study inter- and intraspecific variability.
      The ITS contains the genes coding for tRNA(Ile) and tRNA(Ala) and its total
      length is 547 nucleotides. In six out of eight sequenced clones, there is a
      duplication of 29 nucleotides, surrounding the 5' end of the tRNA(Ile).

PMID- 7522853
TI  - Common acute lymphoblastic leukaemia-lymphoma expressing cytokeratin: a case
      report.
AB  - This report presents a case of common acute lymphoblastic leukaemia-lymphoma
      expressing low molecular weight cytokeratin but no leukocyte common antigen
      (CD45) in a 57-year-old man. The unusual morphology and clinical course together
      with the aberrant immunohistochemical results suggested a diagnosis of
      undifferentiated carcinoma. A detailed immunohistochemistry study on frozen and
      paraffin sections and molecular analysis prevented a diagnostic mistake.

PMID- 7522855
TI  - New therapeutic options in prostatic enlargement.
AB  - Benign prostatic hyperplasia occurs in the majority of men past middle age.
      Transurethral prostatectomy has stood the test of time, but it may not be
      suitable for some men by virtue of concurrent medical problems or because
      patients prefer to avoid the risks and complications associated with surgery.
      This article outlines some of the alternative therapeutic options that are
      available.

PMID- 7522856
TI  - Expression of inducible nitric oxide synthase by neurones following exposure to
      endotoxin and cytokine.
AB  - In the CNS, nitric oxide (NO) has been implicated as both a mediator of
      neurotoxicity and a neuromodulator. The inducible NO synthase (iNOS), thought to
      mediate toxic effects of NO, has been attributed to glial cells in the CNS. We
      now report that cerebellar granule cell neurones can be stimulated by
      lipopolysaccharide and interferon-gamma to express iNOS in vitro, as demonstrated
      by reverse transcription-polymerase chain reaction and fluorescent in situ
      hybridisation. The expression of both constitutive NO synthase (cNOS) and iNOS by
      neurones suggests that NO has diverse functions in the brain, and supports the
      possibility that iNOS plays a role in neuronal damage and inflammation following
      activation of brain microglia and production of cytokines.

PMID- 7522857
TI  - Effects of antidepressants on the inward current mediated by 5-HT3 receptors in
      rat nodose ganglion neurones.
AB  - 1. Effects of three different categories of antidepressants, imipramine
      (tricyclic), fluoxetine (selective 5-hydroxytryptamine (5-HT) uptake inhibitor),
      phenelzine and iproniazid (monoamine oxidase (MAO) inhibitor) on the inward
      current mediated by 5-HT3 receptors were investigated in rat nodose ganglion
      neurones. The whole-cell patch-clamp technique was used for recording the 5-HT
      current. 2. All the antidepressants tested inhibited the peak 5-HT current. The
      inhibition gradually reached a steady level and the recovery was incomplete when
      antidepressants were removed. IC50 values for imipramine, fluoxetine and
      phenelzine were 0.54 microM, 1.3 microM and 4.2 microM respectively. The
      correspondent Hill coefficients were 0.9, 0.87 and 0.92. 3. The antidepressants
      examined increased the rate of 5-HT current desensitization. IC50 values for
      imipramine, fluoxetine and phenelzine on the decrease in desensitization time
      constant were 0.11 microM, 0.18 microM and 2.4 microM respectively. The
      correspondent Hill coefficients were 0.9, 1.14 and 1.06. 4. Intracellular
      applications of the protein kinase inhibitor, H-7 (100 microM), GDP-beta-S (2 mM)
      and the calcium chelator BAPTA (20 mM) did not affect the 5-HT current and the
      actions of antidepressants on 5-HT current. 5. These results suggest that the 5
      HT3 receptor is an acting site for the therapeutic use of antidepressants. The
      present observation is also helpful in explaining the analgesic effect of
      antidepressants seen in pain clinics.

PMID- 7522858
TI  - Mepacrine-induced inhibition of the inward current mediated by 5-HT3 receptors in
      rat nodose ganglion neurones.
AB  - 1. With the whole-cell patch clamp technique, the effect of the antimalarial
      drug, mepacrine (quinacrine) on the inward current mediated by 5-HT3 receptors (5
      hydroxytryptamine (5-HT)-induced current) was investigated in isolated nodose
      ganglion neurones of the rat. 2. 5-HT and the selective 5-HT3 receptor agonists,
      2-methyl-5-HT and m-chlorophenylbiguanide elicited an inward current which
      reversed at around 0 mV and quickly desensitized to a steady state level. 3.
      Mepacrine dose-dependently inhibited the peak current induced by 5-HT with an
      IC50 of 2.1 microM and an apparent Hill coefficient of 0.99. 4. Mepacrine
      increased the decay rate of the 5-HT-induced current. 5. The effect of mepacrine
      on the 5-HT-induced current was reversible and not dependent on membrane
      potential. The reversal potential of the 5-HT-induced current was not affected.
      6. Intracellular mepacrine had no significant effect on the 5-HT-induced current
      and did not block the extracellular action of mepacrine. 7. Concentration
      response curves in the presence and absence of mepacrine suggest a non
      competitive inhibition of 5-HT-induced current by mepacrine.

PMID- 7522860
TI  - A comparison of intravenous NBQX and GYKI 53655 as AMPA antagonists in the rat
      spinal cord.
AB  - 1. The effects of intravenous administration of two alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) antagonists were studied on responses of
      single neurones to iontophoretically applied excitatory amino acids. The tests
      were performed on spinal neurones in alpha-chloralose anaesthetized, spinalized
      rats. 2. Both the quinoxaline, NBQX (2-16 mg kg-1) and the 2,3-benzodiazepine,
      GYKI 53655 (2-8 mg kg-1) dose-dependently decreased responses to AMPA. 3. Both
      compounds were short acting, with half-recovery times of 15 min for NBQX and 7
      min for GYKI 53655. 4. The selectivity for responses to AMPA over those to N
      methyl-D-aspartate (NMDA) was significantly poorer for systemic NBQX than for
      either systemic GYKI 53655 or iontophoretic NBQX, suggesting that systemic NBQX
      may be converted to a less selective metabolite. 5. GYKI 53655 is therefore
      likely to be a more valuable tool than NBQX for the study of AMPA receptor
      mediated processes in vivo.

PMID- 7522859
TI  - A role for endogenous histamine in interleukin-8-induced neutrophil infiltration
      into mouse air-pouch: investigation of the modulatory action of systemic and
      local dexamethasone.
AB  - 1. When injected into a 6-day-old mouse air-pouch, human recombinant interleukin
      8 (IL-8; 0.03-3 micrograms) induced, in a dose-dependent fashion, an accumulation
      of neutrophils which could be reliably assessed 4 h after the injection. No
      protein extravasation was measured above the values obtained with the vehicle
      alone (carboxymethylcellulose, CMC, 0.5% w/v in phosphate-buffered solution,
      PBS). 2. The IL-8 effect (routinely evaluated at 1 microgram dose) was inhibited
      neither by local administration of actinomycin D (1 microgram) nor by systemic
      treatment with indomethacin (1 mg kg-1, i.v.), BWA4C (5 mg kg-1, p.o.),
      methysergide (6 mg kg-1, i.p.) and RP67580 (2 mg kg-1, i.p.). 3. Treatment of
      mice with the H1 antagonist, mepyramine (1-10 mg kg-1, i.p.) resulted in a dose
      dependent inhibition of the cell accumulation elicited by the chemokine, with a
      maximal reduction of approximately 50-60%. The mepyramine effect was not due to a
      non specific reduction of neutrophil function, since treatment with this drug (6
      mg kg-1, i.p.) did not modify the cell infiltration measured in response to a
      challenge with interleukin-1 beta (20 ng) or with the vehicle CMC to any extent.
      Moreover, treatment of mice with mepyramine did not modify cell counts in a
      peripheral blood film with respect to controls. Two other H1 antagonists,
      chemically unrelated to mepyramine, diphenhydramine (9 mg kg-1, i.p.) and
      triprolidine (0.5 mg kg-1, i.p.), inhibited IL-8-induced migration to a similar
      extent (approximately 50-60%), whereas the H2 antagonist, ranitidine (5 mg kg-1,
      i.p.) was without effect. 4. The concept that endogenous histamine could be
      involved in the IL-8 effect was strengthened in two ways: (i) addition of
      histamine (0.2-2 microg) to a small dose of IL-8 (0.3 microg) potentiated the
      cell elicitation induced by the chemokine without having any effect on its own;
      (ii) IL-8-induced neutrophil accumulation was greatly impaired in animals
      depleted of mast cell amines by sub-chronic (5 day) treatment with compound 48/80
      according to an established protocol.5. The glucocorticoid dexamethasone (Dex; 1
      50 microg per mouse, i.v., corresponding approximately to 0.03-1.5 mg kg-1, given
      i.v. 2 h prior to challenge with IL-8) potently inhibited neutrophil infiltration
      with an approximate ED50 of 5 microg per mouse (~ 0.3 mg kg-1 , i.v.). Passive
      immunisation of mice with a polyclonal sheep serum raised against the steroid
      inducible anti-inflammatory protein lipocortin 1 (LCl)abolished the inhibitory
      action of Dex whereas a control serum was without effect.6. Local administration
      of Dex at a dose which was ineffective when given systemically (1 microg) also
      reduced neutrophil migration induced by IL-8, either alone or in combination with
      histamine. This local inhibition (~50%), also seen with hydrocortisone (30
      microg), was prevented by the concomitant administration of the steroid
      antagonist RU38486 (10 microg) indicating the involvement of glucocorticoid
      receptor in the response.7. These findings characterize further the mechanisms
      underlying PMN recruitment induced by IL-8 in vivo, and point to a role for
      histamine. The anti-inflammatory action of the glucocorticoids, as in some other
      models, appears to be LCl-dependent when these drugs are given systemically and
      LCl independent when the steroids are given locally.

PMID- 7522861
TI  - The effect of allosteric antagonists in modulating muscarinic M2-receptor
      function in guinea-pig isolated trachea.
AB  - 1. We have assessed the influence of a range of synthetic cationic polypeptides
      with putative inhibitory actions at prejunctional muscarinic M2-receptors on
      electrical field stimulation-induced contraction of guinea-pig isolated tracheal
      preparations. Electrical field stimulation of epithelium-denuded guinea-pig
      trachea resulted in frequency-dependent contractile responses. As expected,
      tracheal smooth muscle sensitivity to electrical field stimulation was increased
      in tissues pretreated with the muscarinic M2-receptor antagonist, gallamine. In
      contrast, gallamine did not significantly alter the contractile potency to
      acetylcholine. 2. Unlike gallamine, the synthetic cationic polypeptides, poly-L
      arginine, poly-L-lysine, poly-D-lysine, the cationic dye ruthenium red and the
      anionic polysaccharide, heparin, failed to increase significantly tracheal smooth
      muscle sensitivity to electrical field stimulation. 3. Poly-L-arginine, ruthenium
      red and heparin had no effect on the contractile response to exogenously applied
      methacholine. 4. These data are consistent with the concept that in guinea-pig
      tracheal smooth muscle, gallamine is an allosteric antagonist of guinea-pig
      tracheal muscarinic M2-receptors, whereas the various cationic polypeptides and
      the polyanion, heparin, are not.

PMID- 7522865
TI  - Staining and in vitro toxicity of dithizone with canine, porcine, and bovine
      islets.
AB  - Dithizone (DTZ) is a recognized diabetogenic agent in vivo, and a supravital
      stain commonly used for identification of islets to be used for transplantation.
      In the present studies, we compared DTZ staining of freshly isolated and cultured
      canine, bovine, and porcine islets, and the effect of DTZ on the function and
      viability of islets. Incubation with DTZ resulted in staining of canine and
      porcine islets, but no discernible staining with bovine islets. Insulin content
      of porcine, canine, and bovine islet was 2.0 +/- 0.2, 2.2 +/- 0.3, and 1.9 +/-
      0.2 mU/EIN, indicating a lack of correspondence of DTZ staining and insulin
      content. Seven days of culture with canine islets resulted in > or = 50%
      reduction of DTZ stained cells. Exposure to DTZ at 50 micrograms/mL resulted in a
      maximal number of stained cells in preparations of purified islets (80-85%;
      counted after dispersion), a lower percentage of cells stained faintly at 20
      micrograms/mL (50-55%), with no discernible staining at 10 micrograms/mL.
      Prolonged exposure of islets (4-48 h) to 20 micrograms/mL DTZ led to reduced
      insulin secretion and islet cell death. Incubation of canine or porcine islets
      with 100 micrograms/mL of DTZ for 0.5 h resulted in a dramatic loss of viability
      and diminished insulin secretory function, which was not reversed with continued
      culture. The concentration dependence of toxic effects paralleled the
      concentration dependence of cellular staining. The minimally effective staining
      concentration (20 micrograms/mL) also resulted in a loss of viability. An
      additional assessment of DTZ toxicity was made using the RIN-38 beta-cell line,
      which shows no discernible staining with DTZ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522866
TI  - Pore morphology effects on the fibrovascular tissue growth in porous polymer
      substrates.
AB  - The feasibility of developing biodegradable polymer scaffolds to engineer tissues
      was investigated by studying the effects of pore size on the dynamics of
      fibrovascular tissue ingrowth. Tissue advanced into amorphous poly(L-lactic acid)
      porous substrates faster as the pore diameter increased. Porous cylindrical
      devices of 13.5 mm diameter, 5 mm thickness, and approximately 500 microns pore
      size were filled completely by tissue 5 days postimplantation. Although
      prevascularized devices possessed minimal void volume for cell seeding to
      regenerate metabolic organs, they hold promise in the regeneration of tubular
      tissues by relying on the epithelization of prevascularized grafts.

PMID- 7522864
TI  - Typical and atypical NK1 tachykinin receptor characteristics in the rabbit
      isolated iris sphincter.
AB  - 1. A contraction of the rabbit isolated iris sphincter smooth muscle follows
      activation of either tachykinin NK1 or NK3 receptors. We have here characterized
      the pharmacological activity profiles of various tachykinin receptor agonists
      considered to have NK1-receptor-preferring activity in this preparation. 2. Two
      groups of NK1-receptor-preferring agonists could be distinguished in terms of a
      common pharmacological profile. The first group (Group 1) included [Glp6,L-Pro9]
      SP(6-11) (septide), [Glp6]-SP (6-11), substance P methyl ester, delta
      aminovaleryl-[L-Pro9, N-MeLeu10]-SP(7-11) (GR73632), and [Apa9-10]-SP. The second
      group (Group 2) included [Pro9]-SP, substance P, physalaemin and ranamargarin. 3.
      Under control conditions, the responses to Group 1 agonists were relatively fast
      in offset (time for reversal of maximal responses, 11.2-18.2 min), and were
      antagonized by NK1-receptor-selective antagonists (range of pKB estimates vs
      various agonists; GR82334, 7.1-8.2; (+/-)-CP-96,345, 8.9-9.5; RP67580, 7.0-7.4).
      Following incubation of the tissue with phenoxybenzamine (20 microM, 10 min), the
      affinity of GR82334, tested against the Group 1 agonists, substance P methyl
      ester and septide, was not significantly different (P < 0.05; n = 7-18) to that
      determined in untreated tissues (substance P methyl ester pKB 7.5 +/- 0.1 and 7.2
      +/- 0.2, respectively; septide 7.7 +/- 0.2 and 7.9 +/- 0.2, respectively).
      Further, response offset times (5.0-8.5 min) were little reduced as compared to
      those observed in untreated tissues. 4. Under control conditions, the response to
      Group 2 agonists was markedly slow in offset (times for reversal of maximal
      responses, 51.4-70.4min), and was not attenuated significantly by the NK1
      receptor-selective antagonists GR82334 (I MicroM), (+/-)-CP-96,345 (0.1 MicroM)
      or RP67580 (1 MicroM). In contrast,after phenoxybenzamine pretreatment, responses
      to Group 2 agonists reversed rapidly (times for reversal of maximal responses,
      13.1-24.2 min), and were now antagonized by GR82334 (pKB estimates, 6.4-7.1).5.
      The responses to the NK3-receptor-selective agonist Succ-[Asp6,Me-Phe8]-SP(6-l1)
      (senktide) were relatively fast in offset (time for reversal of maximal response
      was 18.6 +/- 1.7 min) and were not inhibited by GR82334 (10 MicroM; n = 5). The
      contractile response resulting from co-application of the Group 1 agonist,
      septide together with senktide, did not exhibit prolonged response offset
      kinetics.6. Assuming simple competition at equilibrium, these data from the
      rabbit iris smooth muscle could be explained either by interaction of the various
      ligands with two separately-existing NK1 receptor-subtypes or -isoforms; or
      alternatively by a preferential interaction of the two agonist groups with
      different binding domains on a common NK1 receptor.

PMID- 7522863
TI  - Involvement of apamin-sensitive K+ channels in antigen-induced spasm of guinea
      pig isolated trachea.
AB  - 1. In order to examine whether K+ channels play a role in antigen-induced airway
      responses, the effect of K+ channel blockers on antigen-induced airway smooth
      muscle contraction and mediator release was examined in vitro in guinea-pigs
      actively sensitized with ovalbumin (OA). 2. Tracheal strips from sensitized
      animals were suspended in organ baths under a resting tension of 1 g and
      isometric tension was continuously measured. Cumulative concentration-response
      curves to OA (0.1-1000 ng ml-1) or histamine (10 nM-1 mM) were obtained in the
      presence and absence of K+ channel blockers. 3. OA (10, 100 or 1000 ng ml-1) was
      incubated with minced lung tissues from the same animals for 15 min in the
      presence and absence of K+ channel blockers, and released histamine and
      leukotriene C4 (LTC4) in the incubating medium were measured. 4. Apamin, a small
      conductance Ca(2+)-activated K+ channel (PK,Ca) blocker, (0.1, 0.3 and 1 microM)
      significantly inhibited OA-induced smooth muscle contraction, while charybdotoxin
      (ChTX, 10 nM), an intermediate and large conductance PK,Ca blocker, and
      iberiotoxin (IbTX, 3 nM), a large conductance PK,Ca blocker, were without effect.
      Apamin (0.3 microM) had no effect on exogenously administered histamine-induced
      airway smooth muscle contraction, suggesting that the inhibition of OA-induced
      contraction by apamin did not occur at the smooth muscle level. 5. The inhibition
      of OA-induced contraction by apamin (0.3 microM) was not significantly affected
      by pretreatment with a leukotriene antagonist, ONO-1078 (10 microM), but was
      abolished by pretreatment with a histamine H1-receptor blocker, pyrilamine (1
      microM). 6. Apamin by itself (up to 0.1 MicroM) had no effect on spontaneous
      histamine release from minced lung tissues. Histamine release induced by low and
      intermediate concentrations of OA (10 and 100 ng ml-1)was significantly
      suppressed by apamin pretreatment (P<0.05 and P<0.001), whereas LTC4 release was
      not affected. ChTX (0.1 MicroM) and IbTX (10 nM) had no significant effect on
      either spontaneous or OA (100 ng ml-1)-induced histamine release.7. These results
      suggest that apamin partially but substantially inhibits antigen-induced smooth
      muscle contraction, presumably by inhibiting antigen-induced histamine release
      from airway mast cells through small conductance PKca closure.

PMID- 7522862
TI  - Lack of effect of microinjection of noradrenaline or medetomidine on stimulus
      evoked release of substance P in the spinal cord of the cat: a study with
      antibody microprobes.
AB  - 1. Experiments were performed on barbiturate anaesthetized, spinalized cats to
      investigate the effect of microinjected noradrenaline or medetomidine on the
      release of immunoreactive substance P in the dorsal spinal cord following
      peripheral nerve stimulation. The presence of immunoreactive substance P was
      assessed with microprobes bearing C-terminus-directed antibodies to substance P.
      2. Noradrenaline or medetomidine were microinjected into the grey matter of the
      spinal cord, near microprobe insertion sites, at depths of 2.5, 2.0, 1.5 and 1.0
      mm below the spinal cord surface with volumes of approximately 0.125 microliters
      and a concentration of 10(-3) M. 3. In the untreated spinal cord, electrical
      stimulation of the ipsilateral tibial nerve (suprathreshold for C-fibres)
      elicited release of immunoreactive substance P which was centred in and around
      lamina II. Neither noradrenaline nor medetomidine administration in the manner
      described produced significant alterations in this pattern of nerve stimulus
      evoked release. 4. In agreement with recent ultrastructural studies these results
      do not support a control of substance P release by catecholamines released from
      sites near to the central terminals of small diameter primary afferent fibres.

PMID- 7522867
TI  - A solid-state 2H NMR investigation of purine motion in a 12 base pair RNA duplex.
AB  - Solid-state 2H NMR spectroscopy has been used to investigate the base dynamics of
      a RNA oligonucleotide with a defined sequence, [r(CGCGAAUUCGCG)]2, which contains
      the RNA analogue of the EcoRI binding site. The C8 protons of all purines in the
      self-complementary dodecamer were exchanged for deuterons. The quadrupole-echo
      lineshapes and spin-lattice relaxation times as a function of hydration for the
      sample in the form of the Na salt have previously been reported. In that study
      the 2H NMR lineshapes and T1 values of [r(CG*CG*A*A*UUCG*CG*)]2 were compared
      with those of the analogously labeled DNA sequence, [(CG*CG*A*A*TTCG*CG*)]2 (Wang
      et al., J. Am. Chem. Soc. 114, 6583, 1992). It was concluded that the amplitudes
      of purine motion for DNA and RNA are similar at all hydration levels; however,
      the rate difference observed at low-hydration levels may or may not persist at
      high hydration. Here the internal motions of the purine bases in the RNA oligomer
      have been thoroughly investigated. Three models were used to simulate the motion:
      (1) two-site jump, (2) diffusion in a cone, and (3) restricted diffusion on the
      surface of a cone. The purine motion is best simulated by the restricted
      diffusion on a cone model with an amplitude of +/- 9.5 degrees and a rate between
      8.0 x 10(6) rad/s at 90% RH and 8.4 x 10(8) rad/s at 0% RH. This small amplitude
      and fast rate of purine motion for RNA are similar to previous results obtained
      for DNA purines.

PMID- 7522868
TI  - Application of the magnetization-inversion-transfer technique to the transport of
      7Li+, 23Na+, and 39K+ ions through the gramicidin channel and the M2 delta
      transmembrane domain of the nicotinic acetylcholine receptor.
AB  - The magnetization-inversion-transfer NMR technique has been used to determine the
      activation enthalpy (delta H not equal to) for the transport of the 7Li+, 23Na+,
      and 39K+ ions through the gramicidin channel incorporated into vesicle membranes.
      The activation enthalpy obtained for the overall transport of the monovalent
      cations was found to be in agreement with the selectivity order and single
      channel ion conductance values. Furthermore, the magnetization-inversion-transfer
      technique was also found to be applicable to the channel formed from a synthetic
      peptide having the same amino acid sequence as the M2 delta transmembrane segment
      of the nicotinic acetylcholine receptor.

PMID- 7522870
TI  - [Use of Streptomyces levoris lytic enzymes for isolation of group-specific
      antigen from streptococcal cells].

PMID- 7522869
TI  - [Eradication of poliomyelitis from the American continent].
AB  - A strategy to eradicate poliomyelitis from America was developed in 1985 by the
      PAHO. The last case of poliomyelitis due to wild virus was detected in August
      1991 in the Andean region of Peru. The main strategies used to eradicate polio
      are: 1) attainment of high immunization levels, 2) biannual National Vaccination
      Campaigns with OPV in all poliomyelitis infected countries, 3) organization in
      all America countries of effective surveillance of AFP, 4) setting up of a
      laboratory network for the isolation of the wild poliovirus from cases and
      contacts' stools samples and 5) the organization of a rapid response, to the
      occurrence of any new case with door to door vaccination (Mop-up). These
      strategies have been recommended by the WHO for Global Eradication of
      Poliomyelitis by the Year 2000. The next step in the Americas is to confirm the
      eradication of poliomyelitis. An ICPEC has been organized and the condition
      required to certify the eradication is the absence of cases of virologically
      confirmed indigenous poliomyelitis by a period of at least three years in the
      context of continued adequate surveillance. Four elements will be taken into
      consideration when confirming the eradication of poliomyelitis: 1) the
      surveillance of AFP, 2) the surveillance of wild poliovirus, 3) active searches
      for AFP cases in areas of risk, such as those areas with poor surveillance, or
      where there have been compatible cases, 4) documentation of mop-up operations in
      areas of risk.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522871
TI  - Care at the core.

PMID- 7522872
TI  - Similarity of the American Urological Association Symptom Index among men with
      benign prostate hyperplasia (BPH), urethral obstruction not due to BPH and
      detrusor hyperreflexia without outlet obstruction.
AB  - OBJECTIVE: To compare the specificity of the American Urological Association
      (AUA) Symptom Index for benign prostatic hyperplasia (BPH) versus other
      urodynamically verified micturitional dysfunction in men. PATIENTS AND METHODS:
      Fifty-seven consecutive men who had been referred for video-urodynamic evaluation
      of voiding symptoms were evaluated. The patients were divided into three groups:
      (i) BPH group (n = 24); (ii) non-BPH obstructed group (n = 20; nine bladder neck
      obstruction, 11 bulbous urethral stricture); and (iii) detrusor hyper-reflexia
      group: detrusor hyper-reflexia without outlet obstruction (n = 13). RESULTS: The
      mean AUA symptom score for the BPH group was 18.9 (range 7-28). The mean score
      for the 20 non-BPH obstructed group was 17.6 (range 4-28) and the mean score for
      the 13 men with detrusor hyper-reflexia was 20.5 (range 12-27). There was no
      statistical difference in the AUA symptom score among the three groups.
      CONCLUSION: The AUA Symptom Index does not specifically identify BPH or bladder
      outlet obstruction. The index cannot differentiate the site of obstruction as
      noted by the similar scores among men with BPH from those with bladder neck
      obstruction and urethral strictures. Moreover, The AUA Symptom Index scores are
      similar between men with voiding symptoms secondary to bladder dysfunction and
      bladder outlet obstruction.

PMID- 7522873
TI  - Procoagulant properties of benign and malignant prostatic tissue.
AB  - OBJECTIVE: To determine the factor-X activating procoagulant activity (FXAA) of
      prostatic tissue removed at transurethral resection in a specific chromogenic
      assay. PATIENTS AND METHODS: FXAA was extracted from transurethrally resected
      prostatic tissue using a cryofragmentation technique. Tissue from 50 patients
      with prostate cancer was analysed and compared with that from 36 control patients
      with benign prostatic-hypertrophy. Enzyme activities were assayed in a two stage
      chromogenic assay and correlated with conventional markers of tumour
      aggressiveness. RESULTS: FXAA was found to be significantly lower (P < 0.001) in
      tissue from malignant prostates compared with benign prostatic hypertrophy
      tissue. Loss of FXAA was also related to Gleason grade (P < 0.03), percentage of
      chips involved by tumour (P < 0.04) and bone scan status (P < 0.02). Using
      antibody inhibition tests this procoagulant was characterized as being a factor
      VII/tissue factor complex. CONCLUSIONS: Malignant change in the prostate is
      associated with a reduction in FXAA and this may be an important factor in
      prostatic tumour growth and dissemination.

PMID- 7522874
TI  - The long-term outcome of patients who relapse after chemotherapy for non
      seminomatous germ cell tumours.
AB  - OBJECTIVE: To examine the long-term survival of a group of patients with non
      seminomatous germ cell tumours, who relapse after chemotherapy and are retreated
      with a cisplatin and etoposide-based regimen. PATIENTS AND METHODS: At the
      Charing Cross Hospital between 1979 and 1988 38 patients in relapse were seen.
      The median interval after primary therapy was 8 months. They were treated with an
      intensive cisplatin and etoposide-based regimen with cycles repeated at 7-10 day
      intervals, and with surgery in 22 patients. RESULTS: Forty-seven per cent of
      patients entered a second complete remission and 88% of these remain disease
      free. The overall survival was 46% with a median follow-up of more than 4.3
      years. Surgery was performed in 14 of 18 patients who entered a second complete
      remission. Adverse risk factors before initial chemotherapy and the time to
      relapse did not predict outcome but patients with unresectable radiological
      masses after relapse therapy had a poor outcome despite normalization of serum
      tumour markers. The tumours of 68% of patients initially treated with cisplatin
      based regimens and 62% of patients who also received etoposide remained
      responsive to conventional doses of these drugs at relapse. CONCLUSIONS: This
      study demonstrates that there is a group of patients with relapsed teratoma who
      can be cured without the need for very high dose chemotherapy and autologous bone
      marrow rescue.

PMID- 7522876
TI  - Antigenic analysis of hematopoiesis: a review.
AB  - The ability to immunophenotype the heterogeneous populations of cells within bone
      marrow has given investigators the tools to identify, enumerate, and isolate
      cells of any lymphohematopoietic lineage. These cells can, in turn, be studied in
      morphologic, growth, biochemical, and molecular biological assays, and used for
      clinical transplantation, with or without in vitro expansion. Although the map of
      normal marrow lymphohematopoiesis has been largely determined, there is still
      some controversy regarding the identity and maturation pathways of
      lymphohematopoietic progenitors and stem cells. The currently available
      information on this area is reviewed and interpreted in this article.

PMID- 7522875
TI  - Gene transfer into human hematopoietic progenitor cells: a review of current
      clinical protocols.
AB  - Recent reviews by Clay Smith (1992) in this journal and by W. French Anderson
      (1990) and A. Dusty Miller (1992) have described the technologies used for gene
      transfer, the potential applications of the approach, and the safety issues that
      require consideration. This review will have a narrower focus. It will deal
      specifically with current and forthcoming clinical protocols for gene transfer
      into hemopoietic progenitor cells, because a major goal of gene therapy for
      malignant and nonmalignant disease is to transfer and express genes on a long
      term basis in these cells or their progeny.

PMID- 7522878
TI  - Ex vivo expansion and gene therapy using cord blood CD34+ cells.
AB  - CD34+ cells can be efficiently isolated from cord blood by sequential Percoll,
      Ficoll-Hypaque, and immunomagnetic bead separation. This population, containing
      up to 25% progenitor cells and 0.2-1% stem cells, defined by a long-term culture
      initiating cell (LTC-initiating cell) assay, can be expanded in vitro in the
      presence of a specific combination of cytokines resulting in a > 100,000-fold
      increase in cells, a > 2,000-fold increase in progenitors, and an 18- to 20-fold
      increase in LTC-initiating cells. These latter populations can be efficiently
      transfected with a retroviral vector expressing a mutated dihydrofolate-reductase
      gene that confers methotrexate resistance.

PMID- 7522877
TI  - Evaluation of a novel automated protocol for the collection of peripheral blood
      stem cells mobilized with chemotherapy or chemotherapy plus G-CSF using the
      Fresenius AS104 cell separator.
AB  - Forty-seven peripheral blood stem cell (PBSC) collections were carried out on
      patients mobilized with chemotherapy and 63 on patients mobilized with
      chemotherapy plus G-CSF (Filgrastim), using the Fresenius AS104 cell separator
      and a novel automated PBSC collection protocol. As expected, cell yields were
      significantly higher in the series mobilized using chemotherapy plus G-CSF. The
      low platelet and red blood cell contamination permitted freezing of the apheresis
      product without further manipulation, other than plasma removal in both series.
      In patients mobilized with chemotherapy we obtained a MNC and a hemopoietic
      progenitor (CFU-GM, BFU-e, and CD34+ cells) collection efficiency comparable or
      superior to those reported by Bender (1992) with the Baxter CS3000 Plus after
      mobilization with cyclophosphamide. A significant decrease in MNC, BFU-e, and
      CD34+ cell collection efficiency was found in patients mobilized with
      chemotherapy plus G-CSF compared to those obtained in patients mobilized with
      chemotherapy alone. Ten patients achieved a prompt and stable engraftment after
      high dose chemotherapy and the infusion of cryopreserved PBSC collected using
      this protocol. Studies are in progress in order to improve MNC and hemopoietic
      progenitor collection efficiency in patients mobilized with G-CSF to obtain a
      graft in no more than one or two procedures.

PMID- 7522880
TI  - Separation of hematopoietic progenitor cells from human umbilical cord blood.
AB  - Human umbilical cord blood (HUCB) is a rich source of hematopoietic progenitor
      cells (HPC). Nevertheless, it has been previously reported that attempts to
      enrich for HPC resulted in substantial loss of progenitor cells. We have
      developed a cell processing technique for HUCB using 3% gelatin sedimentation and
      the AIS MicroCELLectorSBA and CD34. By this technique, we were able to deplete
      red blood cells (RBC) and obtain a partial T cell depletion, while maintaining 70
      90% of the HPC. The results indicate that it may be possible to manipulate cord
      blood without significant loss of HPC, thus enhancing its utility for
      transplantation.

PMID- 7522879
TI  - Modulation of the growth of hematopoietic human stem cells by growth factors:
      comparison of umbilical cord blood with bone marrow.
AB  - The growth of cord blood and bone marrow myeloid mononuclear cells in response to
      single and multiple growth factors has been examined. Single factors such as IL
      3, IL-6, GM-CSF, and stem cell factor did not optimally stimulate growth of cord
      blood CFU-GM. However a synergistic stimulation was observed when the factors
      were combined. This effect was seen in both the presence and absence of added
      fetal calf serum.

PMID- 7522881
TI  - Immunomagnetic positive selection and colony culture of CD34+ cells from blood.
AB  - Immunomagnetic separation has been used to enrich CD34-positive cells in
      umbilical cord blood. Cell purities were increased from 0.59% preseparation to
      92.7% postseparation (n = 16) with a mean yield of 75.7%. CFU were enriched 127
      fold by immunomagnetic separation. Addition of combinations of recombinant growth
      factors resulted in cloning efficiencies of greater than 50%.

PMID- 7522882
TI  - Human umbilical cord blood CD34+ cell purification with high yield of early
      progenitors.
AB  - Human umbilical cord blood CD34+ cells were purified using a two-step procedure
      by elimination of the soybean agglutinin-binding cells and by a positive panning
      selection with a CD34 monoclonal antibody. The isolated fraction was 88-97% pure
      CD34+ cells. A yield of 48.5% was obtained when comparing the number of cells
      recovered in the CD34(+)-purified fraction and the number of CD34+ cells detected
      in the initial mononuclear cell fraction. By flow cytometry, we observed that the
      CD34+ cells that were not recovered were those that had the lower expression of
      CD34 antigen and were therefore the more mature cells. A high recovery of CFU
      GEMM progenitors (73.9%) was also observed. These data suggest the possibility of
      purifying CD34+ umbilical cord blood cells for clinical applications, in
      particular for umbilical cord blood banking.

PMID- 7522883
TI  - Commentary: prospects for standardization of stem cell determination within
      Europe.

PMID- 7522884
TI  - Positive selection of human blood cells using improved high gradient magnetic
      separation filters.
AB  - High gradient magnetic separators (HGMS) create magnetic field gradients that can
      be used to attract much smaller and less magnetic particles than those required
      for conventional magnetic separation techniques. As a result cells can be labeled
      with submicron magnetic particles and still be separated using an HGMS filter.
      Typically, HGMS filters consist of random arrays of wire such as stainless steel
      wool. Wire elements arranged regularly in a filter should allow more efficient
      separation of cells. Filters were constructed containing ordered wire arrays
      composed of 430 series stainless steel wire mesh with wire diameters of 50, 100,
      or 150 microns. The ability of these filters to separate T cells from peripheral
      blood mononuclear cell suspensions was tested and found superior to random arrays
      of 302 series stainless steel wire (Thomas et al, 1992). Target cells recognized
      by OKT5 monoclonal antibody were cross-linked to dextran-iron particles of
      approximately 20 nm in diameter. Separation conditions were optimized and after
      one passage through the filter 88% of the OKT5+ cells were recovered in the
      enriched fraction with 85% purity (%OKT5+). Multiple passages (3 times) could
      achieve 99% purity with 68% recovery. Variations in separation flow rate had a
      large effect on the balance between purity and recovery. Optimum separation
      efficiencies were achieved only when > 10(8) cells were processed. The primarily
      cause of nonspecific entrapment of CD8- cells was not nonspecific magnetic
      labeling of cells but the physical (nonmagnetic) characteristics of the
      filter/filter chamber.

PMID- 7522885
TI  - Measurement of CD34+ cells in bone marrow by flow cytometry.
AB  - A procedure is described for the measurement of the %CD34+ progenitor cells in
      bone marrow using directly conjugated antibodies. Staining cells with anti
      CD45.FITC in conjunction with anti-CD34.PE allows the CD45- nucleated red blood
      cells and the CD45++ lymphocytes and monocytes to be separated from the CD45+
      progenitor cells. Granulocytes are separated from the CD34+ cells based on
      differences in side scatter properties. A gated acquisition of CD34+ cells is
      used to define the boundaries of the CD34+ population in a plot of forward
      scatter vs side scatter and in a plot of anti-CD45.FITC vs anti-CD34.PE. Use of
      these regions during analysis reduces background staining and allows for a
      consistent identification of a CD34+ population. Acquisition of 50,000 cells
      provides adequate precision of the %CD34+ measurement. Acquisition and analysis
      procedures are presented for use of both a Becton Dickinson FACScan flow
      cytometer and a Coulter EPICS Profile II flow cytometer.

PMID- 7522886
TI  - In vitro properties of purified human stem cell candidates.
AB  - Serum-free cultures supplemented with IL-6, IL-3, steel factor, and
      erythropoietin support extensive production of erythroid cells from purified bone
      marrow stem cell candidates which are themselves maintained in number in such
      cultures. In this study, the mechanism responsible for the observed maintenance
      of primitive hematopoietic cells in rapidly proliferating suspension cultures was
      examined. The following models were considered: (1) proliferating cells represent
      a small minority of cells at start of culture (large quiescent pool), (2) self
      renewal of primitive cells (balanced by loss through differentiation and death),
      and (3) asymmetrical divisions (each division of a primitive cell yielding one
      equally primitive daughter cell and one less primitive, i.e., committed daughter
      cell). To discriminate between these various models, the proliferative behavior
      of purified CD34+ CD71 cells was studied at a population level using the
      fluorescent membrane dye PKH26 and at a single cell level by studying cultures of
      individually sorted CD34+ CD45RAloCD71lo bone marrow stem cell candidates. The
      results from these experiments indicate that the majority of purified stem cell
      candidates do not rapidly proliferate in response to the combination of growth
      factors used and that limited production of CD34+ cells compensates for the loss
      of such cells in culture. These observations have to be taken into account in the
      development of clinical useful strategies for the expansion of primitive
      hematopoietic bone marrow cells ex vivo.

PMID- 7522887
TI  - Immunomagnetic separation of CD34+ cells from human bone marrow, cord blood, and
      mobilized peripheral blood.

PMID- 7522889
TI  - Transplantation of hematopoietic stem cells.

PMID- 7522892
TI  - Preparation of samples for flow cytometric analysis.

PMID- 7522894
TI  - Assessment of hematopoietic cell differentiation by multidimensional flow
      cytometry.

PMID- 7522888
TI  - Direct isolation and expansion of human CD34+ hematopoietic stem cells.
AB  - The isolation and expansion of CD34+ cells has numerous applications as
      supportive therapy for cytopenias that occur postchemotherapy. In this report, we
      describe a simple system to directly isolate and culture human CD34+ cells. Using
      this system, CD34+ cells isolated from bone marrow were cultured in the presence
      of GM-CSF, G-CSF, erythropoietin, stem cell factor, IL-1, IL-3, and IL-6. Cell
      expansions up to 100-fold were noted during the first 2 weeks of culture with
      high maintenance of CD34+ cells during the first week of culture. Maximal
      expansions of progenitors were observed at one week of culture, with, on average,
      20-fold increases in CFU-GM number. The results support the feasibility of CD34+
      cell expansion for clinical application.

PMID- 7522895
TI  - The impact of harvest center on quality of marrows collected from unrelated
      donors.
AB  - The total number and distribution of nucleated cells in harvested bone marrow are
      potentially important determinants of patient outcome following bone marrow
      transplantation. In order to assess whether marrows collected from predominantly
      unrelated donors at Georgetown University Medical Center (GUMC) were different in
      cellular content from marrows collected at harvest centers outside of GUMC, we
      compared the nucleated cell counts and mononuclear cell subset distribution
      (CD34, CD3, CD4, CD8, CD19 antigen-positive cell content) of 10 consecutive
      marrows harvested at GUMC to 10 unrelated donor marrows from outside harvest
      centers. Significantly higher nucleated cell counts and CD34 antigen-positive
      cell content and significantly lower CD3 and CD4 antigen-positive T-cell numbers
      were demonstrated among the marrows harvested at GUMC. These results confirmed
      significant variability in marrow collection practices between GUMC and 10
      different outside harvest centers and suggest that strict adherence to a specific
      collection procedure, involving small volume marrow aspirations and multiple
      puncture sites, results in a product with a high number of early hematopoietic
      progenitor cells and minimal contamination by peripheral blood. These data
      further suggest the need for careful monitoring of individual unrelated donor
      marrow collection centers' practices to optimize the quality of the harvested
      marrow.

PMID- 7522890
TI  - Hematopoietic growth factors for the mobilization of peripheral blood stem cells.
AB  - Hematopoietic growth factors can be used for the mobilization of peripheral blood
      stem cells that have the proliferative capacity to restore long-term
      hematopoiesis after myeloablative therapy. An association between specific
      cytokines and the composition of the blood-derived progenitor cells has not yet
      emerged. It appears that yield and composition of PBSC are influenced far more by
      the individual than by the use of specific growth factors. Our future studies
      will focus on how many and what kind of stem cells are needed for high-dose
      regimens with different myelotoxicity. In parallel, autografts will be assessed
      for contaminating tumor cells, if disease- or clone-specific markers are
      available. This approach may then provide the rationale for the increasing use of
      PBSC for autografting.

PMID- 7522893
TI  - Flow cytometric analysis of peripheral blood stem cells.

PMID- 7522896
TI  - Isolation of human CD34+ peripheral blood stem cells using an immunomagnetic
      positive selection system: prior monocyte depletion using a nylon-wool column.
AB  - An immunomagnetic separation system has been used to collect CD34+ cells in
      mobilized blood after treatment with a nylon-wool column. Cell purities were
      increased from 2.6% preseparation to 94.6% postseparation, with a mean yield
      45.2% (n = 4). Forty percent of CD34+ cells separated by the immunomagnetic
      procedure formed colonies in the presence of hematopoietic growth factors in a
      limiting dilution assay. Eleven percent of these clones proliferated to over
      10(5) cells and contained megakaryocytes.

PMID- 7522891
TI  - The use of G-CSF or GM-CSF mobilized peripheral blood progenitor cells (PBPC)
      alone or to augment marrow as hematologic support of single or multiple cycle
      high-dose chemotherapy.
AB  - High dose chemotherapy with autologous bone marrow support (ABMT) can achieve
      prolonged relapse-free survival in relapsed lymphomas, leukemias, and certain
      solid tumors. The principal morbidity and mortality relate to the infectious
      complications that occur during the 3-4 week aplasia until the marrow autograft
      recovers. Progenitor cells can be mobilized into the peripheral blood compartment
      by hematopoietic growth factors, used alone or after chemotherapy. We describe
      four trials using cytokine-mobilized peripheral blood progenitor cells (PBPC). In
      the first trial, PBPC collected after GM-CSF administration were used to augment
      marrow. Reconstitution of trilineage marrow function occurred promptly, resulting
      in short hospital stays and fewer platelet transfusions. In a second study, GM
      CSF/chemotherapy-mobilized PBPC were used as the sole hematopoietic support
      during high dose chemotherapy. Granulocyte and platelet reconstitution was rapid.
      Time to hematopoietic recovery, transfusion requirements, and duration of
      hospital stay were all significantly improved for the patients receiving PBPC
      compared with similar patients receiving marrow alone. While most patients
      experienced prompt hematopoietic recovery they showed sluggish platelet
      engraftment. The next two trials built on the observation that a few PBPC alone
      could support both granulocyte and platelet recovery and were designed to test
      the feasibility of sequential high-dose therapies. In one trial, PBPC given with
      and without marrow made it possible to deliver two sequential cycles of high-dose
      therapy. The second trial utilized PBPC plus cytokines to deliver four cycles of
      dose-intensive chemotherapy at doses that could not be given with cytokine
      support alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522897
TI  - Cytokine-mediated expansion of 5-FU resistant peripheral blood stem cells and
      bone marrow: self-renewal and commitment capacity.
AB  - To further characterize the primitive stem cell subpopulation present in
      chemotherapy mobilized peripheral blood stem cells (PBSC), we evaluated the
      functional characteristics of 5-FU-resistant PBSC and normal bone marrow (BM)
      cells after 7 days incubation with IL-1 + IL-3+SCF. The resulting 5-FU-resistant
      cells were evaluated for (1) the production of GM-CSF-responsive clonogenic
      elements (CE), (2) the production of IL-3+GM-CSF-responsive CE, and (3) their
      self-renewal capacity (production of IL-1+IL-3+SCF-responsive CE). We also
      evaluated the percentage of CD34+ cells, the percentage of cells in S phase of
      the cell cycle, and the number of nucleated cells before and after cytokine
      mediated expansion. We demonstrated an overall loss in nucleated cells after
      cytokine-mediated expansion in all cell fractions. We demonstrated a
      significantly greater increase in the percentage of CD34+ cells in the 5-FU
      resistant PBSC fraction as compared to 5-FU-resistant BM cells (p = 0.012). We
      also showed that 5-FU-resistant PBSC have a greater capacity for self-renewal,
      amplification of IL-3+GM-CSF-responsive progenitors, and the production of
      committed GM-CSF-responsive progenitors as compared with BM cells, but this did
      not reach statistical significant. These results suggest that PBSC contain a
      truly primitive stem cell with an enhanced self-renewal and differentiative
      capacity that is recruited by 5-FU resistance and IL-1+IL-3+CSF-mediated
      expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522899
TI  - Transplantation of CD34+ hematopoietic progenitor cells.
AB  - Sixty-six stage IV breast cancer patients received high dose chemotherapy
      followed by autologous transplantation of CD34-positive(+) cells obtained from
      the bone marrow and/or granulocyte colony stimulating factor (G-CSF)-mobilized
      peripheral blood. Grafts were examined for the presence of tumor using
      conventional histology and immunocytochemical staining. Patients achieved a
      granulocyte count of 500 x 10(9)/liter 10-12 days posttransplant, with a platelet
      count of > 20 x 10(9)/liter in 14-15 days. Enrichment of CD34+ cells from the
      peripheral blood progenitor cell (PBPC) collections resulted in a 1.3 to 4.0 log
      depletion of breast cancer cells from the graft.

PMID- 7522898
TI  - Peripheral blood stem cell collection after mobilization with intensive
      chemotherapy and growth factors.
AB  - Peripheral blood has become an alternative to bone marrow as a source of stem
      cells for transplantation. One of the major disadvantages of peripheral blood as
      a source is the low concentration of stem cells. For successful engraftment, the
      infusion of at least 6 x 10(8) nucleated cells per kg is required, a cell number
      obtained by 6-8 cell pheresis sessions. This cell number contains approximately
      0.1% CD34 cells equivalent to 600,000 CD34 cells. It is known that chemotherapy
      and hematopoietic growth factors increase the concentration and total number of
      progenitor cells in the peripheral blood. In breast and lung cancer patients we
      are using two cytoreductive regimens: cytoxan 2 g/m2 + platinol 90 mg/m2, and VP
      16 600-900 mg/m2+ platinol 90 mg/m2, respectively, in conjunction with G-CSF for
      stem cell mobilization. At the time of hematopoietic recovery, between day 13 and
      16, the absolute number of CD34+ cells increases in 75% of the patients more than
      20-fold, from 5,000 to at least 100,000/ml blood, and to more than 40-fold, to
      200,000/ml, in 54% of the patients. Therefore, 3.4-7.5 ml blood contains up to
      750,000 CD34+ cells, the minimum number of CD34 cells/kg body weight infused when
      steady-state collected peripheral blood cells are used. Since we use a minimum of
      3 x 10(6) CD34+ cells/kg body weight, 15,000 ml of mobilized blood are required.
      This amount can often be obtained by collecting 500 ml blood by phlebotomy in 2-3
      separate sessions, which is an easy and cost-effective method for the patient.

PMID- 7522900
TI  - Establishment of a cellular assay system for G protein-linked receptors: coupling
      of human NK2 and 5-HT2 receptors to phospholipase C activates a luciferase
      reporter gene.
AB  - A functional cellular assay system was developed for the detection of substances
      modulating the activity of G protein-coupled receptors, linked to the
      phospholipase C second messenger system. The human adenocarcinoma cell line A549
      was transformed with the Photinus pyralis luciferase gene under the control of
      the ICAM-1 gene 5'regulatory region and, subsequently, stably transfected with
      the human neurokinin 2 (NK2) receptor gene. The ICAM-1 promoter is known to be
      inducible via the phospholipase C signal transduction pathway. In this NK2
      receptor test cell line, expression of luciferase was inducible by neurokinin A
      and other NK2-specific agonists. The order of potency of the three neurokinins
      substance P, neurokinin A and neuromedin K was consistent with published data and
      results from ligand binding studies performed with the same NK2 test cell line.
      The agonistic effect of neurokinin A could be inhibited in a dose-dependent
      manner by simultaneous addition of NK2-specific antagonists or protein kinase C
      inhibitors. Similarly, a stable test cell line expressing the human serotonin 2
      receptor was established. Agonist-induced luciferase expression in this cell line
      was abolished in the presence of 5-HT2-specific antagonists. These cellular assay
      systems can be employed for the identification of competitive, non-competitive
      and allosteric modulators of the NK2 and the 5-HT2 receptor, and they represent
      prototypes for analogous test cell lines for other phospholipase C-coupled
      receptors.

PMID- 7522902
TI  - Receptors that couple to 2 classes of G proteins increase cAMP and activate CFTR
      expressed in Xenopus oocytes.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR), a Cl- channel
      activated by phosphorylation, was expressed in Xenopus oocytes along with various
      combinations of several other components of the cAMP signalling pathway.
      Activation of the coexpressed beta 2 adrenergic receptor increased cAMP and led
      to CFTR activation. The activation of CFTR (1) requires only short (15 s)
      exposure to isoproterenol, (2) occurs for agonist concentrations 100-1000 fold
      lower than those that produce cAMP increases detectable by a radioimmunoassay,
      (3) requires injection of only 5 pg of receptor cRNA per oocyte, and (4) can be
      increased further by coexpression of cRNA for adenylyl cyclase type II or III or
      for Gs alpha. In addition, CFTR activation and cAMP increases by beta 2
      activation were enhanced by activation of the coexpressed 5HT1A receptor, which
      is thought to couple to Gi. The additional activation by the 5HT1A receptor was
      enhanced by coexpression of adenylyl cyclase type II but not with type III and
      may proceed via the beta gamma subunits of a G protein. The sensitivity of the
      assay system is also demonstrated by responses to vasoactive intestinal peptide
      and to pituitary adenylate cyclase-activating polypeptide in oocytes injected
      with cerebral cortex mRNA.

PMID- 7522903
TI  - Effects of long-chain fatty acids on the channel activity of the nicotinic
      acetylcholine receptor.
AB  - We have analyzed the effect of free fatty acids on the function of the
      acetylcholine receptor (AChR) at the single-channel level, using the patch-clamp
      technique. Long-chain fatty acids, in the presence of albumin as a carrier, were
      applied to intact cells or to the cytoplasmic surface of excised membrane
      patches. In the latter case, AChR channels underwent immediate changes in their
      behaviour and only very brief opening events were apparent. This could be
      accounted for by a four-fold reduction in the channel mean open time, with no
      significant changes occurring in the conductance. An increase in the duration of
      intermediate closed intervals and a decrease in the burst duration were also
      observed. The modification appeared not to be critically dependent on the degree
      of saturation of fatty acyl chains. Addition of free fatty acids in the absence
      of albumin, as well as treatment of the excised membrane patches with
      phospholipase A2, resulted in complete inhibition of AChR channel activity. In
      intact cells, fatty acids could reach and affect AChR channels in the plasmalemma
      under the patch pipette when added from outside the patch-clamped area. The fatty
      acid-modified AChR was still able to undergo desensitization. The open channel
      probability was higher than 0.8 for 100 microM agonist, decreasing to 0.4 in the
      fatty acid-modified receptors. The results are discussed within the framework of
      the hypothesis that some lipophilic compounds exert their action on the AChR
      lipid interface (the "annulus") (see Barantes, 1993).

PMID- 7522901
TI  - Effect of deletion mutations on the function of CFTR chloride channels.
AB  - Mutations in the gene for the cystic fibrosis transmembrane conductance regulator
      (CFTR) cause cystic fibrosis (CF). CFTR contains two membrane-spanning domains
      (MSDs), two nucleotide-binding domains (NBDs), and a unique R domain; CFTR
      functions as a Cl- channel regulated by phosphorylation and by nucleoside
      triphosphates. To study the domains of CFTR involved in Cl- channel function, we
      expressed mutants lacking various domains and assayed cAMP-stimulated Cl- channel
      activity using the halide-sensitive fluorophore, 6-methoxy-N-(3'-sulfopropyl)
      quinolinium. We previously reported that deletion of part of the R domain
      (residues 708-835) produced Cl- channels that were constitutively open. Here we
      show that more extensive deletions within the R domain failed to generate
      functional CFTR Cl- channels; the portion of protein that could be deleted
      without destroying function corresponds to sequences that are not conserved in
      related proteins. In contrast, when we deleted the two NBDs (either alone,
      together, or in combination with the R domain), we did not observe functional Cl-
      channels. CFTR has a unique carboxyl terminus that is conserved across species.
      However, truncation of the carboxyl terminus (up to, but not including, NBD2)
      produced a regulated anion permeability similar to that of wild-type CFTR,
      suggesting that this region is not essential for channel function. Expression of
      two CF-associated nonsense mutants (G542X and W1316X) also failed to generate
      functional CFTR Cl- channels. These results help define structure:function
      relationships for CFTR and identify the domains that are required for Cl- channel
      function.

PMID- 7522905
TI  - Cancer of the colon and rectum in the West Midlands, 1957-1981.
AB  - Between 1957 and 1981, 49,904 patients with large bowel cancer were registered at
      the Birmingham Cancer Registry. The annual incidence was 24.5 per 100,000
      population for colonic cancer and 18.4 per 100,000 for that of the rectum. The
      annual number of patients increased by 41.9 per cent. The age-adjusted 5-year
      survival rate was 26.4 per cent for colonic carcinoma and 28.2 per cent for
      rectal cancer. Between 1977 and 1981 these rates increased significantly to 30.3
      and 30.0 per cent respectively (P < 0.01). Stage for stage, colonic cancer was
      associated with longer survival than that of the rectum. Curative and palliative
      resection rates increased, especially for anterior resection. The operative
      mortality rate remained constant at 8 per cent. Despite increases in palliative
      resection rates 50 per cent of these patients required a stoma. Treatment was not
      undertaken in 37.4 per cent of patients. The end results of treatment are little
      better than those reported previously from this registry.

PMID- 7522908
TI  - Sources and seasonal variability of mutagenic agents in the Barcelona City
      aerosol.
AB  - Organic extracts (dichloromethane) isolated from airborne particulate matter,
      collected in two sampling sites located in the Barcelona City, were mutagenic in
      the Salmonella typhimurium (TA98 +/-S9) bioassay. The highest direct-acting
      mutagenicity (69-78 rev m-3) was detected during fall and spring, which
      corresponds to the highest levels of mutagenic nitroarenes (248 to 350 pg m-3).
      On the other hand, the highest level of indirect-acting mutagenicity was obtained
      in summer, paralleling with the highest concentrations of polycyclic aromatic
      ketones and polycyclic aromatic quinones. Furthermore, the sources of PAH in the
      urban particulate matter were estimated from the ratio of the less reactive
      components (i.e. benzofluranthenes/benzo[e]pyrene, indeno[1,2,3
      cd]pyrene/benzo[ghi]perylene, methylphenantherenes/phenanthrene) and reflected a
      predominance of pyrolytic mobile sources (i.e. vehicular emissions).
      Nevertheless, a contribution of stationary sources in winter was also apparent.
      Finally, the seasonal variability of polycyclic aromatic ketones, quinones,
      aromatic lactones and aldehydes reflected a major contribution of the atmospheric
      transformation processes from related PAH rather than a direct emission from
      combustion sources.

PMID- 7522906
TI  - Randomized placebo-controlled double-blind study of three aprotinin regimens in
      primary cardiac surgery.
AB  - The serine proteinase inhibitor aprotinin significantly reduces postoperative
      blood loss in patients requiring cardiac surgery using cardiopulmonary bypass.
      This study compared two low-dose regimens with administration of high-dose
      aprotinin and a control protocol to determine whether the dose of aprotinin could
      be greatly decreased but still maintain efficacy after primary cardiac surgery.
      Some 100 patients were randomly assigned to one of four groups: control group
      (0.9 per cent saline placebo, n = 25); high-dose group (aprotinin 2 x 10(6)
      kallikrein inactivator (KI) units intravenous patient bolus and 0.5 x 10(6) KI
      units h-1 plus 2 x 10(6) KI units into pump prime, n = 25); prime group
      (aprotinin 2 x 10(6) KI units added to the pump prime, n = 24); and patient group
      (aprotinin 10(6) KI units intravenous patient bolus plus 10(6) KI units added to
      the pump prime, n = 26). Only patients from the high-dose and patient groups had
      reduced intraoperative blood loss, but patients from all three aprotinin-treated
      groups demonstrated a significant decrease in median postoperative blood loss
      compared with the control group (high-dose 350 ml, prime 420 ml, patient 340 ml
      versus control 780 ml; P < 0.001). There was an even greater reduction in
      measured median postoperative haemoglobin loss within the chest drains in the
      treated compared with the control patients (high-dose 15 g, prime 24 g, patient
      14 g versus control 47 g; P < 0.001). These decreases were statistically the same
      for all the treated groups; it is possible to lower the dose of aprotinin to
      approximately one-third of the currently recommended dosage and still obtain
      significantly reduced postoperative blood loss in primary cardiac surgery.

PMID- 7522907
TI  - Sequence specific cleavage of messenger RNA by a modified ribonuclease H.
AB  - Ribonuclease H (RNase H) is an endonuclease that cleaves only the RNA strand of
      an RNA-DNA hybrid to produce 5'-phosphate and 3'-hydroxy termini and lacks useful
      sequence specific recognition properties. A mutant form of the E. coli enzyme has
      been prepared that is suited for selective chemical modification at a site
      proximal to the substrate binding region. The chemical derivatization involves
      the formation of a disulfide linkage to a modified octadeoxyribonucleotide. The
      conjugate retains only 0.3% of the normal sequence independent RNase H activity
      demonstrating that substrate recognition can be modulated by a covalent
      appendage. A beta-globin RNA transcript containing a sequence complementary to
      that of the octadeoxyribonucleotide was cleaved in a catalytic fashion to two
      products upon treatment with the conjugate. The selectivity in the phosphodiester
      bond cleavage mediated by the conjugate was found to be different than that
      displayed by the nonderivatized enzyme. These results demonstrate the potential
      of semi-synthetic RNase H conjugates for mechanistic studies and their
      application as RNA targeted diagnostic or therapeutic agents.

PMID- 7522909
TI  - Nematode test to estimate the hazard potential of solved contaminations.
AB  - The acute toxicity of lindane, pentachlorophenol and a fluortenside was examined
      using a recently developed ecotoxicity test with the terrestrial nematode species
      Panagrellus redivivus. The exposure was performed in aqueous solution over an
      investigation period of 96 h. For lindane a time dependent decrease of the
      survival rate (LC50 after 96 h: 0.4 mg/l) was observed which indicates a high
      cuticular permeability of the insecticide. For pentachlorophenol the LC50 (96 h)
      was 13 mg/l, for the fluortenside a value of 110 mg/l was determined.

PMID- 7522904
TI  - The structure of a neutralized virus: canine parvovirus complexed with
      neutralizing antibody fragment.
AB  - BACKGROUND: Members of the Parvovirus genus cause a variety of diseases in
      mammals, including humans. One of the major defences against viral infection is
      the presence of neutralizing antibodies that prevent virus particles from
      infecting target cells. The mechanism of neutralization is not well understood.
      We therefore studied the structure of canine parvovirus (CPV) complexed with the
      Fab fragment of a neutralizing antibody, A3B10, using image reconstruction of
      electron micrographs of vitrified samples, together with the already known
      structure of CPV from X-ray crystallographic data. RESULTS: The structure of the
      complex of CPV with Fab A3B10 has been determined to 23 A resolution. The known
      CPV atomic structure was subtracted from the electron density of the complex, and
      the difference map was used to fit the atomic coordinates of a known Fab
      fragment, HyHEL-5. The long axis of each Fab molecule is oriented in a near
      radial direction, inclined away from the two-fold axes. The viral epitope
      consists of 14 amino acid residues found in loops 1, 2 and 3 on the capsid
      surface, which include previously identified escape mutations. CONCLUSIONS: The
      mode of Fab binding suggests that the A3B10 neutralizing antibody cannot bind
      bivalently to the capsid across the two-fold axes, consistent with the
      observation that whole A3B10 antibody readily precipitates CPV. Since Fab A3B10
      can also neutralize the virus, mechanisms of neutralization such as interference
      with cell attachment, cell entry, or uncoating, must be operative.

PMID- 7522910
TI  - The L-arginine: nitric oxide pathway.
AB  - The L-arginine: nitric oxide pathway is widely recognized as an important
      regulator of cell function and communication in a variety of physiological and
      pathophysiological situations. Recent advances in the biochemistry and molecular
      biology of nitric oxide synthases have contributed significantly to our
      understanding of the regulation of nitric oxide synthesis in health and disease.
      This pathway has been implicated in the pathogenesis of septic shock,
      hypertension, and atherosclerosis as well as in the antihypertensive action of
      converting enzyme inhibitors. Progress in this field, which spans the
      cardiovascular, immune, and nervous systems, has been rapid, and its full
      potential is yet to be realized.

PMID- 7522912
TI  - Structural and functional aspects of P-glycoproteins and related transport
      proteins.
AB  - The emergence of multidrug resistance in tumor cells is caused by the expression
      of P-glycoprotein. P-glycoprotein has a unique structure formed by two homologous
      halves, each encoding six putative transmembrane segments and one nucleotide
      binding fold. This structural arrangement has been conserved in a large number of
      eukaryotic and prokaryotic membrane transport systems, which together form the
      ATP binding cassette superfamily. These membrane transporters act on different
      groups of substrates in different cell types and organisms. The combined
      molecular analysis of these proteins has shed light on the mechanism by which P
      glycoprotein acts on structurally unrelated groups of chemotherapeutic drugs and
      has allowed the identification of the protein domain responsible for the common
      mechanism of transport and recognition of substrate molecules. The function of P
      glycoprotein in normal tissues remains intriguing and is discussed in this
      review.

PMID- 7522911
TI  - Water channels.
AB  - The movement of water across cell membranes has been an active area of research
      for more than 100 years and is of fundamental importance in the normal water
      metabolism of all terrestrial animals. The objective of this review is to
      integrate recent data obtained from the isolation and molecular cloning of water
      channel proteins, with functional information provided by biophysical
      measurements of membrane water transport. Whereas the water permeability of most
      cell membranes can be accounted for by the diffusion of water across the lipid
      bilayer, other cells, including the erythrocyte as well as certain cells in renal
      epithelia, possess specialized water channels. Water channels are composed of
      specialized proteins that create highly selective aqueous pores across cell
      membranes. Data concerning the distribution, permeability, and function of these
      various water channels will greatly enhance our knowledge of how water is
      transported across cell membranes.

PMID- 7522913
TI  - Neurotransmitters. Elusive glutamate receptors.
AB  - Kainate-preferring glutamate receptors appear to be abundant in the central
      nervous system. We have recently begun to understand their properties, but their
      functions remain to be described.

PMID- 7522914
TI  - Channel regulation. Ion channel control by tyrosine phosphorylation.
AB  - Recent results implicate tyrosine phosphorylation in the control of ion channels
      and neuronal modulation.

PMID- 7522915
TI  - Cell adhesion. Fibronectin and integrin knockouts come unstuck.
AB  - Mice with homozygous null mutations in the genes encoding fibronectin or the
      alpha5 integrin subunit die as embryos. The types of embryonic defect confirm
      some ideas about fibronectin function but cast doubt on others.

PMID- 7522917
TI  - Practical ribozymes. Making ribozymes work in cells.
AB  - Ways are being found to increase the efficacy of ribozymes in cells, offering
      hope that they may soon begin to fulfill their promise as new reagents for
      inactivating specific RNAs in cells.

PMID- 7522916
TI  - RNA selection. Aptamers achieve the desired recognition.
AB  - In vitro selection procedures can generate RNA molecules, known as aptamers, that
      bind pre-determined ligands with an affinity and selectivity comparable to highly
      evolved protein molecules.

PMID- 7522918
TI  - Molecular evolution. Unlocking the secrets of retroviral evolution.
AB  - Studies of a small circular plasmid found in the mitochondria of the fungus
      Neurospora crassa shed unexpected light on the evolution of RNA viruses into
      retroviruses.

PMID- 7522920
TI  - The role of respiratory tract infections in asthma.
AB  - In this article the author presents the latest data on the role of bacterial and
      viral respiratory tract infections in the pathogenesis of bronchial asthma. The
      effect of microorganisms and their products on immunological and non
      immunological mechanisms of cell mediator release, cytokine activity, bronchial
      hyperreactivity and acute and late asthmatic reactions are discussed. As this
      brief review shows, the role of respiratory infections in the development of
      different types of asthma is very important.

PMID- 7522919
TI  - Sinusitis in the critical care patient.
AB  - A frequently overlooked source of sepsis in the critical care patient is the
      paranasal sinuses. These patients are typically unable to communicate and,
      therefore, the usual findings of sinus infection, such as facial pain and
      complaints of purulent drainage, will be absent. Sepsis may be the first
      manifestation of such infection. Nasotracheal intubation is the most important
      predisposing factor to developing sinusitis in these patients. The clinician,
      therefore, must maintain a high index of suspicion in any patient with fever of
      unknown origin. Radiologic studies, including plain sinus radiographs, or
      preferably, a computed tomography scan, will usually show the presence of fluid
      or inflammation. Lavage of the maxillary sinus is helpful both to verify the
      presence of infection and to obtain culture material. These infections tend to be
      polymicrobial, and often display a predominance of Gram-negative organisms,
      particularly Pseudomonas aeruginosa. Treatment includes removal of all nasal
      tubes and institution of appropriate antibiotics, along with decongestant
      therapy. In some cases, surgical drainage will be necessary. For patients who are
      immunocompromised, or requiring intubation for > 7 days, the nasotracheal route
      is best avoided.

PMID- 7522921
TI  - Vaginocervical stimulation attenuates hindpaw shock-induced substance P release
      into spinal cord superfusates in rats.
AB  - The present study was designed to elucidate the mechanism in the spinal cord by
      which vaginocervical stimulation (VS) attenuates responses to noxious
      stimulation. This was accomplished by testing the hypothesis that VS reduces
      noxious stimulation-induced release of substance P at the level of the spinal
      cord. Noxious foot shock significantly increased the release of substance P
      (measured using radioimmunoassay) into superfusates of the lumbosacral spinal
      cord region in urethane-anesthetized rats. VS applied concurrently with foot
      shock significantly attenuated the release of substance P compared to the foot
      shock-only condition. In addition, substance P levels were significantly lower
      after the VS-only condition than after the no stimulation or foot shock-only
      conditions. These findings indicate that VS may produce analgesia, at least in
      part, by suppressing the release of substance P within the spinal cord.

PMID- 7522922
TI  - Synaptic structure and connectivity of serotonin terminals in the ventral
      tegmental area: potential sites for modulation of mesolimbic dopamine neurons.
AB  - Microinfusion of serotonin (5-hydroxytryptamine; 5-HT) into the ventral tegmental
      area enhances the release of dopamine in the nucleus accumbens, a major target of
      midbrain dopamine neurons. We examined the synaptic basis for 5-HT modulation of
      neurons in the ventral tegmental area which either (i) project to the nucleus
      accumbens or (ii) contain the catecholamine synthesizing enzyme tyrosine
      hydroxylase, a marker of dopamine neurons in this brain region. In the first
      study, immunoperoxidase labeling of 5-HT in the ventral tegmental area was
      combined with retrograde transport of gold particles following unilateral
      injections of the tracer into the nucleus accumbens of adult rats. The gold
      particles had been previously coupled to wheat germ agglutinin conjugated to
      inactive horseradish peroxidase. Gold particles were enlarged for visualization
      using a silver enhancement procedure. By brightfield microscopy, retrogradely
      labeled neurons contained black punctate granules within their perikarya and
      proximal processes. The labeled cells were scattered ipsilateral to the injection
      within the paranigral and parabrachial subdivisions of the ventral tegmental
      area. Both regions also contained 5-HT immunoreactive varicosities. By electron
      microscopy, irrespective of the ventral tegmental subdivision, 5-HT labeling was
      seen primarily in unmyelinated axons and axon terminals. The terminals contained
      small, clear and large dense core vesicles and ranged from 0.3 micron to 1.4
      microns in cross-sectional diameter. 22% (n = 250) of the axon terminals
      containing 5-HT immunoreactivity formed synaptic contacts with neurons containing
      the retrograde label. Of these 5-HT terminals, 16% formed asymmetric type
      contacts and 6% formed symmetric junctions on the retrogradely labeled neurons.
      The remaining 5-HT terminals were either apposed to (but lacked recognized
      synapses on) perikarya and large dendrites containing the retrogradely
      transported protein-gold tracer or contacted unlabeled neurons. In the second set
      of experiments combining immunoperoxidase of 5-HT and immunogold silver for
      tyrosine hydroxylase, 32% (n = 250) of the 5-HT-labeled terminals formed synaptic
      junctions with perikarya or dendrites containing tyrosine hydroxylase
      immunoreactivity. Of these 5-HT terminals, 23% formed asymmetric type junctions.
      The remainder were either symmetric or lacked recognized membrane densities. The
      prominence of asymmetric junctions formed by 5-HT-labeled terminals on neurons
      projecting to the nucleus accumbens and those containing tyrosine hydroxylase in
      the ventral tegmental area suggests a cellular basis for serotonergic excitation
      of mesoaccumbens dopamine neurons. Additionally, the multiplicity of junctions
      formed by 5-HT terminals on targets with or without retrograde labeling or
      tyrosine hydroxylase immunoreactivity is consistent with known diverse
      physiological actions of 5-HT in the tegmental area.

PMID- 7522923
TI  - Transient immunohistochemical labelling of rat retinal axons during Wallerian
      degeneration by a monoclonal antibody to neurofilaments.
AB  - Immunohistochemical labelling with the monoclonal antibody SMI32 to non
      phosphorylated epitopes on neurofilament proteins of high molecular weight class
      was low in rat central optic fibers of controls. After unilateral transection of
      optic nerve, a strong, transient increase of labelling with SMI32 occurred in
      degenerating fibers of optic tract at 2 and 4 days, which then declined at 8 and
      remained low at 21 days. Consequently, immunostaining with SMI32 may serve as a
      positive marker for degenerating fibers in rat optic system.

PMID- 7522924
TI  - Expression of the endothelin-1 and oxytocin genes in the hypothalamus of the
      pregnant rat.
AB  - Endothelin (ET)-1, a neuropeptide and possible neuromodulator, has been found in
      the hypothalamic supraoptic and paraventricular nuclei (SON and PVN) of the rat
      in the distribution of oxytocin (OT) neurons. Within the hypothalamus of the
      pregnant rat, we investigated the developmental expression of the ET-1 gene and
      the possibility of coordinate expression of the ET-1 and OT genes. Blots
      containing hypothalamic mRNAs from 4-, 14-, 18-, and 21-day-old pregnant rats
      were hybridized to a 32P-labeled probe specific to the rat ET-1 gene.
      Hypothalamic tissue contained an ET-1 transcript of approximately 2.3 kb size. ET
      1 mRNA abundance increased significantly in the SON and PVN from early to late
      gestation (P = 0.005 and 0.05, respectively). Blots containing hypothalamic mRNA
      were rehybridized to a 32P-labeled probe specific to exon C of the rat OT gene.
      OT gene expression increased significantly within both the hypothalamic SON (p =
      0.0009) and PVN (P = 0.003) as gestation advanced. The sizes of the hypothalamic
      ET-1 and OT transcript sizes remained unchanged throughout gestation.
      Hypothalamic ET-1 and OT transcripts display stage-specific increases during
      gestation. ET-1 may be a neuroendocrine regulator of pregnancy-related events in
      the rat, and may act alone or in concert with OT.

PMID- 7522925
TI  - Glucocorticoids potentiate the adenylyl cyclase-cAMP system mediated
      immunoreactive beta-endorphin production and secretion from hypothalamic neurons
      in culture.
AB  - Beta-endorphin(beta EP)1-31, a potent opioid peptide of proopiomelanocortin
      (POMC) derivatives, is produced and released from neurons at arcuate nuclei of
      the rat hypothalamus. Although dexamethasone (DM) suppresses the production and
      secretion of POMC related peptides from rat pituitary corticotrophs, the effect
      of glucocorticoids on the function of hypothalamic beta EP neurons remains
      unclear. Employing long term monolayer cultures of neonatal rat hypothalamic
      cells, we report here that 4 day treatment with 10 microM of forskolin increased
      ir-beta EP levels in cell content and culture media by approximately 1.7 (P <
      0.05) and 4.1 times (P < 0.01) above vehicle treated control cultures (mean +/-
      S.E.M., 47.3 +/- 2.6 pg/well and 40.4 +/- 3.0 pg/well; n = 3) respectively.
      Although 4 day treatment with DM alone had little effect on the release and the
      cell content of ir-beta EP, it significantly enhanced forskolin-induced elevation
      of ir-beta EP levels in cell content and in culture media. The effect of DM was
      dose-related and time-dependent, with an EC50 of about 1 nM; at this
      concentration DM enhanced ir-beta EP secretion about 2.1 times (P < 0.01) above
      that induced by 10 microM of forskolin alone. Furthermore, the potentiating
      effect of DM was specifically suppressed by 100 nM of RU38486 (P < 0.01), a
      glucocorticoid receptor antagonist, but not by an equivalent dose of RU28318, a
      mineralocorticoid receptor antagonist. In addition, Northern blot analysis showed
      that forskolin (10 microM) increased the abundance of POMC mRNA 1.4 fold above
      that of vehicle treated control cultures. Whereas by itself, DM (10 nM) had
      little effect on the level of POMC mRNA, it enhanced forskolin-stimulated
      increase of the abundance of POMC mRNA approximately 2.6 times. Moreover, DM also
      augmented 1.6 times (P < 0.05) forskolin-induced but not 3-isobutyl-1
      methylxanthine (IBMX)-induced increase of cAMP production (5.5 +/- 0.4 pmol/well;
      mean +/- S.E.M., n = 3) in the cultures. Taken together, our findings suggest
      that in contrast to the inhibitory effect on pituitary corticotrophs,
      glucocorticoids enhance the production and secretion of beta EP from rat
      hypothalamic neurons by facilitating the stimulatory effect mediated, in part,
      through the adenylyl cyclase-cAMP system.

PMID- 7522926
TI  - Cardiovascular effects of intrathecally administered endothelins and big
      endothelin-1 in conscious rats: receptor characterization and mechanism of
      action.
AB  - In conscious rats, the intrathecal (i.t.) injection of endothelin-1 (ET-1; 65-650
      pmol) and endothelin-3 (ET-3; 162-650 pmol) produced dose-dependent increases of
      mean arterial blood pressure (MAP) accompanied by either a tachycardia or a
      bradycardia. A number of animals died by a sudden respiratory arrest. ET-3 was
      less toxic and less potent than ET-1 on MAP and heart rate (HR) while BQ-3020, a
      selective ETB agonist, had no toxic effect and exhibited only a weak pressor
      effect on blood pressure. The prior i.t. injection of 65 nmol BQ-123, a selective
      ETA receptor antagonist, blocked both the cardiovascular and toxic effects of ET
      1 but failed to modify the cardiovascular effect evoked by i.t. substance P (6.5
      nmol) or to cause intrinsic cardiovascular and toxic effects. While the pressor
      response to ET-1 was significantly inhibited after i.v. injection of
      phentolamine, the bradycardia was blocked by pentolinium. The cardiovascular
      response to ET-1 was, however, unaffected in rats either sympathectomized with 6
      hydroxydopamine or pretreated with capsaicin. Furthermore, big ET-1 (100 pmol)
      caused toxic effects and delayed cardiovascular changes which were prevented by
      the prior i.t. administration of either BQ-123 (65 nmol) or 100 nmol
      phosphoramidon, an endothelin-converting enzyme (ECE) inhibitor. These results
      suggest: (1) that the cardiovascular and toxic effects of i.t. endothelins are
      mediated by ETA receptors in the rat spinal cord; (2) that the pressor response
      and bradycardia are likely due to the activation of the sympatho-adrenal nervous
      system and to a vagal reflex mechanism, respectively; and (3) that a
      phosphoramidon-sensitive ECE converts big ET-1 to ET-1 in the rat spinal cord.

PMID- 7522928
TI  - Identification of pontocerebellar axon collateral synaptic boutons in the rat
      cerebellar nuclei.
AB  - Injections of the orthogradely transported tracer PHA-L into the basilar pontine
      nuclei or reticulotegmental nucleus of hooded rats produced labeling of
      pontocerebellar axons that distributed to the cerebellar cortex and nuclei. EM
      examination of the lateral and interposed cerebellar nuclei revealed that labeled
      pontocerebellar axon terminals formed synaptic boutons in the cerebellar nuclei
      that were morphologically different from the characteristic mossy fiber terminals
      observed in the cerebellar cortex.

PMID- 7522927
TI  - Dorsal root ganglion neurons of embryonic chicks contain nitric oxide synthase
      and respond to nitric oxide.
AB  - We investigated the function of nitric oxide (NO) in dorsal root ganglion (DRG)
      neurons from 10 day embryonic chicks and adult birds. NADPH-diaphorase activity,
      a histochemical marker for nitric oxide synthase (NOS) in paraformaldehyde-fixed
      neurons, and NOS-like immunoreactivity were localized in all neurons in thoracic
      and lumbar ganglia from embryos. However, only a subset of neurons from adults
      contained NOS-like immunoreactivity and NADPH-diaphorase activity. Thus,
      embryonic chick DRG neurons have the potential to synthesize NO in response to
      elevated cytoplasmic Ca2+. We also investigated the ability of dissociated
      embryonic chick DRG neurons to respond to NO by examining the effects of NO
      donors and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) on Ca2+
      current (ICa) using the amphotericin-permeabilized patch-clamp technique: sodium
      nitroprusside (5 microM) reduced ICa to 0.68 +/- 0.06 (mean +/- S.D., n = 5) of
      control, S-nitroso-N-acetylpenicillamine (1 microM) reduced ICa to 0.44 +/- 0.06
      (n = 4) of control, while 8-Br-cGMP (1 mM) reduced ICa to 0.58 +/- 0.22 (n = 5)
      of control. ICa was reduced in every neuron tested and this effect was partially
      reversed after approximately 10 min of washing. Thus, ICa of embryonic chick DRG
      neurons is inhibited by NO, possibly by a cGMP-dependent mechanism. These results
      indicate that all DRG neurons in embryonic chicks contain NOS-like
      immunoreactivity and respond to NO. Further, the percentage of NADPH-diaphorase
      positive neurons is reduced during development.

PMID- 7522929
TI  - Immunosuppressants and calcineurin inhibitors, cyclosporin A and FK506,
      reversibly inhibit epileptogenesis in amygdaloid kindled rat.
AB  - Calcineurin (CaN) immunoreactivity and content increased markedly in kindled rat
      brain, and this increment was due to CaN in the membrane fraction. Investigation
      of the effects of cyclosporin A and FK506 (immunosuppressants which inhibit CaN
      activity in T lymphocytes) in the kindling phenomena showed that the kindling
      stage progression was reversibly blocked by these drugs. These findings suggest
      that calcineurin may play an essential role in acquiring epileptogenesis in
      kindling.

PMID- 7522930
TI  - Pineal nitric oxide synthase: characteristics, adrenergic regulation and
      function.
AB  - Available studies indicate that the adrenergic stimulation of pineal cyclic GMP
      production involves stimulation of guanylyl cyclase activity by nitric oxide (NO)
      derived from arginine. This line of investigation was extended in the present
      study. Using a highly sensitive microassay, it was found that pineal NO synthase
      activity is present at levels approximately 30% of those in the cerebellum, that
      approximately 95% of enzyme activity is cytoplasmic, that the enzyme is
      Ca2+/calmodulin-dependent and that enzyme activity is inhibited by the arginine
      analog NG-nitro-L-arginine methyl ester (L-NAME). Norepinephrine treatment of
      intact glands in culture increased [3H]citrulline formation from [3H]arginine.
      This treatment also increased the formation of an NO-like compound, indicating
      that NO synthase activity in the intact gland is elevated by adrenergic
      stimulation. Studies on the effects of inhibition of NO synthase activity
      indicated that treatments known to inhibit NO synthase activity and the
      adrenergic stimulation of cyclic GMP accumulation did not inhibit adrenergic
      stimulation of pineal cyclic AMP, N-acetyltransferase activity or melatonin
      production. These observations support the hypothesis that NE stimulation of
      pineal cyclic GMP accumulation involves stimulation of a Ca2+/calmodulin
      sensitive form of NO synthase, resulting in enhanced accumulation of NO; and,
      that although NO appears to play a role in the adrenergic stimulation of pineal
      cyclic GMP accumulation, it does not appear to play a critical role in the
      adrenergic stimulation of cyclic AMP, N-acetyltransferase activity or melatonin
      production.

PMID- 7522932
TI  - Differential ability of tachykinin NK-1 and NK-2 agonists to produce scratching
      and grooming behaviours in mice.
AB  - Potent and selective NK-1 and NK-2 agonists as well as compounds with lower
      selectivity and affinity for NK-1 binding sites were compared in their ability to
      produce scratching and grooming behaviours when injected
      intracerebroventricularly in mice. Septide, an agonist with a low affinity for NK
      1 binding sites, [Sar9, Met(O2)11]SP and to a lesser extent [Pro9]SP, two potent
      and selective NK-1 agonists were the most effective drugs in stimulating these
      behaviours. Only high doses of [Apa9,10]SP and [Lys5, Tyr7, Pro8]NKA(4-10), two
      agonists with low affinity for NK-1 binding sites, produced scratching and
      grooming responses. Similarly, only high doses of [Lys5, MeLeu9, NLe10]NKA(4-10),
      a potent NK-2 agonist, produced grooming behaviour. When coinjected with the
      endopeptidase enzyme inhibitor phosphoramidon, the effects of [Apa9,10]SP, [Lys5,
      Tyr7, Pro8]NKA(4-10) and [Pro9]SP were markedly enhanced. Analyses of the potency
      of the different agents to displace 3H-SP binding in mouse subcortical structures
      revealed that the affinities of the agonists for NK-1 receptors are similar to
      those previously reported in rat brain. The efficacy of the agonists at producing
      behavioural responses was not equivalent to their potency to bind to central NK-1
      receptors. These findings therefore suggest that a stimulation of NK-1 but also
      non classical NK-1 receptors are involved in the induction of scratching and
      grooming behaviours.

PMID- 7522933
TI  - Beta A4(25-35) modulates substance P effect on rat skin microvasculature in aged
      rats: pharmacological manipulation using SEC-receptor ligands.
AB  - The primary constituent of the senile plaque core in Alzheimer's disease (AD) is
      the beta-amyloid protein (beta A4). A discrete 11 amino acid fragment of the beta
      A4, beta A4(25-35), has been implicated in mediating in vitro neurotoxicity and
      an inflammatory response surrounding senile plaques in AD via interaction with
      the Serpin Enzyme Complex (SEC) receptor. Substance P (SP), a neuropeptide of the
      tachykinin family and a major mediator of neurogenic inflammation, shows sequence
      homology to beta A4(25-35) and has been shown to protect against the
      neurotoxicity of beta-amyloid. SP also competes with beta A4(25-35) for binding
      to the SEC-receptor. SP neurons have also been found to be depleted in AD. Using
      a blister model of inflammation in the rat hind footpad, we have examined the
      effect of beta A4(25-35) and its interaction with SP in rat skin microvasculature
      and determined age-related changes to these phenomena. In addition,
      pharmacological manipulation of these responses using SEC-receptor ligands
      (peptide 105Y and 105C) was also undertaken. Because of the evidence for co
      existence and co-release of SP and calcitonin gene-related peptide (CGRP) from
      the peripheral terminals of sensory nerves, it was of interest to examine the
      interaction of CGRP with beta A4(25-35) on rat skin microvasculature. beta A4(25
      35) (10 microM) was perfused over the base of a blister raised on the hind
      footpad of anaesthetised young and old rats. This was followed by perfusion of SP
      (1 microM) or CGRP (1 microM) after Ringer's solution. Relative blood flow was
      monitored using a Laser-Doppler Flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522931
TI  - Permissive role of glucocorticoids on interleukin-1 activation of the
      hypothalamic serotonergic system.
AB  - The present study analyses the effect of IL-1 beta (10 ng i.c.v.) on the
      hypothalamic serotonergic system and the modulatory role of glucocorticoids.
      Changes in the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA) were
      recorded in freely moving rats by in vivo voltammetry using chronically implanted
      carbon fiber electrodes (8 microns) in the medial preoptic area. IL-1 beta
      induced a dual increase in 5HIAA levels: a rapid, short-term rise was followed by
      a lasting increase possibly due to newly synthesized IL-1. The synthetic
      glucocorticoid dexamethasone (DEX, 3 mg/kg i.p., 30 min before IL-1 beta),
      prevented the effect of IL-1 beta starting from 150 min, suggesting that it only
      inhibited the second increase. In adrenalectomized rats IL-1 beta had no effect
      but when these rats were given DEX (40 micrograms/kg a day for 3 days) the short
      term increase was restored. The glucocorticoid receptor antagonist RU38486 (25
      mg/kg s.c., 60 min before IL-1 beta) completely prevented IL-1 beta activation of
      the serotonergic system. The results indicate that the glucocorticoids are
      effective inhibitors of IL-1 synthesis but that they play a permissive role on IL
      1 beta induced activation of the serotonergic system.

PMID- 7522934
TI  - Galanin-containing neurons in the solitary nucleus and locus coeruleus of
      spontaneously hypertensive rats are associated with genetic hypertension.
AB  - Spontaneously hypertensive (SHR) rats contained more galanin (GAL) content and
      GAL mRNA in locus coeruleus (LC) at the prehypertensive, but not at the well
      established hypertensive stage, than did age-matched Wistar-Kyoto (WKY) rats.
      However, there was also more GAL content, but not GAL mRNA, in the nucleus
      tractus solitarii (NTS) of SHR rats than WKY rats at both stages. This study
      suggests that galaninergic neurons in the LC and NTS may participate in the
      pathogenesis of genetic hypertension.

PMID- 7522936
TI  - [Interferons as antineoplastic drugs--direct regulatory effects on tumor cells].
AB  - Interferons (IFNs) are a family of pleiotropic cell regulatory molecules and
      members of the cytokine network. Apart from a central role in the body's first
      line defence against infections, they are important in regulation of immune
      responses and may be involved in control of cell growth and differentiation. Over
      the past ten years, clinical trials provided unequivocal evidence that IFNs to
      have anticancer activity, even though this is valid in a restricted range of
      tumours mainly of haematopoietic origin. We currently suppose three ways in which
      IFNs could affect tumour growth: 1. Direct regulatory effects on tumour cells. 2.
      Immunomodulatory effects that enhance or even initiate a host response to the
      tumour. 3. Regulatory effects on host/tumour interaction not associated with
      immune responses. We reviewed the direct regulatory effects of IFNs on tumour
      cells and results of clinical trials of IFNs in cancer therapy. (Tab. 2, Ref.
      85.)

PMID- 7522935
TI  - Expression of the inducible form of nitric oxide synthase by reactive astrocytes
      after transient global ischemia.
AB  - We recently demonstrated that reactive astrocytes express NADPH diaphorase
      activity, a marker for Nitric Oxide Synthase, following transient global ischemia
      (Neuroscience Letters 154: 125-128). There has been little evidence that
      astrocytes express Nitric Oxide Synthase or produce NO (nitric oxide) in vivo;
      although in vitro experiments have shown that cultured astrocytes can produce NO.
      To determine whether reactive astrocytes express inducible form of NOS (iNOS) in
      vivo, we studied the pathological changes of rat hippocampus by
      immunohistochemistry after 10 minutes of transient global ischemia, which results
      in the selective delayed death of CA1 pyramidal cells and marked gliosis in the
      CA1 subfield. In the normal hippocampus, astrocytes express neither NADPH
      diaphorase activity nor iNOS. After ischemia, the temporal and spatial pattern of
      iNOS, NADPH diaphorase, and GFAP are very similar, indicating that reactive
      astrocytes express iNOS. Double staining for NADPH diaphorase and GFAP, or iNOS
      and GFAP confirmed that reactive astrocytes express both NADPH diaphorase
      activity and iNOS immunoreactivity. These changes were observed three day after
      ischemia and increased in prominence from one week to one month. The staining
      pattern of OX42, an antibody that recognizes both microglia and macrophages, is
      spatially and temporally distinct from the pattern of NADPH diaphorase and iNOS
      staining. Thus, we conclude that transient global ischemia induces iNOS primarily
      in reactive astrocytes. This increase in NOS expression and, presumably, NO
      production by reactive astrocytes may play a role in the process of delayed
      neuronal death or in the remodeling responses that occur after ischemic damage.

PMID- 7522937
TI  - [Modification of a panoptic method of staining isolated cells].
AB  - A simple and rapid method of isolated cell staining was achieved by modification
      of the Pappenheim's method. It is based on the following steps: (1) dilution of
      commonly used stock solutions May-Grunwald (1:1), Giemsa-Romanowsky (1.25% v/v),
      (2) reverse sequence of the used staining solutions in comparison with the
      original method, (3) shorter time of procedure (5 min/slide), (4) utilization of
      distilled water of pH 5.1-5.6 for dilution of solutions and rinsing of slides,
      (5) it is not necessary to add serum to cell suspensions. The presented
      histological method is suitable for cytomorphological examination of cells. It
      can be applied in routine hematological laboratories not equipped with cytospins.
      (Fig. 5, Ref. 6.).

PMID- 7522938
TI  - [The volume of the prostate in benign hyperplasia and evaluation of infravesical
      obstruction].
AB  - In a prospective study group of 22 patients we analyzed the relationship between
      the volume of benign prostatic hypertrophy (BPH) and infravesical obstruction. We
      diagnosed obstruction with urodynamic measurement (pressure flow studies) in 16
      patients (72.7%). Volume of BPH was investigated by the transrectal ultrasound.
      We found obstruction in 11 from 14 patients (63.6%) with BPH > or = 30 ml and in
      5 from 8 patients (36.4%) with BPH < 30 ml. The diagnostic accuracy of prostatic
      volume measurement in the diagnosis of infravesical obstruction was only 63.6%.
      The volume of BPH did not correlate with the infravesical obstruction. (Tab. 3,
      Fig. 1, Ref. 14.)

PMID- 7522940
TI  - School performance of children in kinship care.
AB  - This study represents the first comprehensive assessment of the school
      performance of children placed in the care of a relative, an arrangement termed
      kinship care. The educational programs, academic achievement, and cognitive and
      language skills of the children were assessed with a teacher questionnaire and
      standardized tests. Compared to their peers, high rates of grade retention and
      participation in special and remedial education, as well as significant academic
      achievement, cognitive, and language deficits were found. Most teachers, however,
      reported that educational services were appropriate and several interventions had
      proven successful. Analyses of predictor variables showed that placement at a
      later age and fewer children in the home were associated with higher academic
      achievement. Results are reviewed in the context of other foster care studies,
      and recommendations are made regarding future research and educational needs of
      children in kinship care.

PMID- 7522941
TI  - [Immunohistochemical study of neuroendocrine cells and prostate-specific antigen
      in prostate carcinoma].
AB  - In 21 cases of prostate adenocarcinoma and 4 cases of prostate hyperplasia,
      neuroendocrine (NE) cells were studied immunohistochemically with anti
      chromogranin antibody. NE cells were detected in 8 cases (38.8%), in which 4 were
      found positive for serotonin and 2 for glucagon. 25 cases of prostatic specimens
      and 7 cases of nonprostatic adenocarcinomas were labelled with prostate-specific
      antigen (PSA). It was shown that expression of PSA was closely correlated with
      differentiation of prostatic adenocarcinomas. Reaction of PSA was stronger in
      well-moderately differentiated adenocarcinoma than in poorly differentiated one.
      For staining pattern, positive reaction of PSA was located in the apical border
      in well-moderately differentiated adenocarcinoma, but in the cytoplasm and cell
      membrane in poorly differentiated one.

PMID- 7522939
TI  - Value of prostate cancer screening in a comprehensive community cancer center.
AB  - Early detection of prostate cancer may help decrease cancer deaths from this
      disease despite the increased incidence of prostate cancer. In 1990 and 1991 we
      conducted one-day "screens" for prostate cancer. This analysis was undertaken to
      determine the value of the screening procedures for detecting prostate cancer in
      the community. A total of 579 men, aged 39-84 years (mean 58 years), were
      evaluated by digital rectal examination (DRE) by a urologist, serum prostate
      specific antigen (PSA) determination by monoclonal antibody assay, and completion
      of a detailed questionnaire. Forty-eight percent had not seen a physician in over
      2 years; 17% had a 1st- or 2nd-degree relative with prostate cancer. There was a
      25% "suspicious" rate including 76 (13%) men with abnormal DRE only, 48 (8%) with
      abnormal PSA only, and 21 (4%) with abnormal DRE and PSA. Patients with findings
      suspicious for cancer were recontacted by telephone at 2-month intervals for 6
      months to determine outcome because subsequent diagnostic management was at the
      discretion of practicing physicians. By 6 months, 84% of patients with abnormal
      findings had seen a physician as recommended. Of the 76 with abnormal DRE only,
      11 were biopsied and only one cancer was found (9%). Of 48 with an elevated PSA
      only, 19 were biopsied; 11 (58%) had cancer (9/9 positive transrectal ultrasound)
      and 8 had no cancer at biopsy (5/5 negative transrectal ultrasound). Of 21 with
      both tests suspicious, 11 were biopsied and 9 had cancer (82%). Thus, by 6 months
      after each screen there was a 3.5% overall cancer detection rate for the whole
      population screened, a 67% positive biopsy rate among those with an elevated PSA,
      a 45% positive biopsy detection rate among those with an abnormal DRE, and a 51%
      positive biopsy rate among all those biopsied. Eighty percent of the PSA
      elevations were between 4.1 and 10.0 ng/ml. This screening experience yielded
      several new diagnoses of prostate cancer, and the use of serum PSA levels and
      ultrasound-guided biopsy was associated with a high positive biopsy rate for
      cancer.

PMID- 7522942
TI  - [Preparation and antigenic characterization of rat monoclonal antibodies against
      hemorrhagic fever with renal syndrome virus].
AB  - 11 hybridoma cell lines secreting monoclonal antibodies (McAbs) against
      hemorrhagic fever with renal syndrome virus (HFRSV) were obtained in our
      laboratory by immunizing LOU/C rats with HFRSV Chen strain. These rat McAbs were
      characterized by radio-immunoprecipitation and western blotting methods, 2
      directed against glycoprotein G2, 9 against nucleocapsid protein (NP) of HFRSV.
      The results of neutralization (NT) and hemagglutination inhibition(HI) test
      showed that most of the McAbs specific for NP had neither NT nor HI activities,
      but 2 had obvious NT and/or HI activities. It was suggested that there may be
      some neutralizing and hemagglutinating determinants on NP of HFRSV. Two McAbs to
      G2 had HI or/and NT activities. These date indicated that distinct neutralizing
      and hemagglutinating epitopes were located on the G2. Comparative antigenic
      analysis of 20 strains of HFRSV was carried out by immune horseradish peroxidase
      technique using 11 anti-HFRSV rat McAbs. It was found that these McAbs can be
      classified into group, subgroup, apodemus type and subtype specificity to HFRSV.

PMID- 7522943
TI  - The role of cereal and fungal amylases in cereal flour hypersensitivity.
AB  - To investigate the role of cereal alpha and beta-amylase in bakers' asthma, we
      have compared the IgE response of 30 wheat-flour-allergic individuals to barley
      alpha and beta-amylases with that of fungal alpha-amylase using
      radioallergosorbent test (RAST), RAST inhibition assays and Western blotting.
      RAST analysis showed 29 of the 30 subjects with inhalant induced cereal allergy
      had positive IgE to cereal amylases, but only 16 were positive to fungal alpha
      amylase. Regression analysis showed an association between specific IgE to wheat
      flour and to barley alpha-amylase (r = 0.70) and barley beta-amylase (r = 0.92)
      but a poor association with fungal alpha-amylase (r = 0.34). RAST inhibition
      showed minimal crossreactivity between barley alpha or beta-amylase and barley
      and fungal alpha-amylase. Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and Western blotting showed that non-reduced barley
      alpha-amylase had a molecular weight of 54 kDa and barley beta-amylase a
      molecular weight of 64 kDa. Reduced fungal alpha-amylase had a molecular weight
      of 54 kDa. Cereal alpha and beta-amylase appear to be important allergens in
      patients with allergy to flour.

PMID- 7522944
TI  - Cypress pollen allergy. Identification of allergens and crossreactivity between
      divergent species.
AB  - Studies employing sera from 34 subjects allergic to white cypress pine (Callitris
      glaucophylla) pollen identified 18 IgE antibody-binding components in the pollen
      of this species, five of which (MWs approximately 94, 68, 64, 43 and 34 kDa) were
      recognized by all of the sera. Protein blotting and quantitative inhibition
      studies revealed clear cross-reactivity between C. glaucophylla and Cupressus
      sempervirens pollen proteins and striking similarities in the IgE recognition
      band patterns of the two pollens. Inhibition experiments with other pollen
      extracts revealed that sera from C. glaucophylla pollen-allergic subjects can be
      divided into two groups--those inhibited only by extracts from the two
      Cupressaceae pollens and those inhibited both by these pollen proteins and by
      pollen extracts from other species. Most of the crossreactions in the latter
      group cannot be explained on the basis of taxonomic relationships or separate
      sensitizations. As with previous studies on birch and olive pollens, we conclude
      that pollen allergenic crossreactivity is much more wide-ranging than generally
      believed.

PMID- 7522946
TI  - Joint statement on resuscitative interventions. Canadian Medical Association,
      Canadian Hospital Association, Catholic Health Association of Canada.

PMID- 7522945
TI  - Euthanasia, physician-assisted suicide and the ethical care of dying patients.

PMID- 7522947
TI  - Tumor angiogenesis in human lung adenocarcinoma.
AB  - BACKGROUND: Hematogenous metastasis requires angiogenesis within the tumor.
      Previous studies have shown that microvessel counts in histologic sections of the
      primary tumor, which reflect angiogenesis, are correlated with metastasis in
      breast, prostate and Stage I nonsmall cell lung carcinoma. In this study, the
      authors investigated the association between angiogenesis, hematogenous
      metastasis and lymph node metastasis in all stages of lung adenocarcinoma.
      METHODS: Microvessels were highlighted by immunostaining endothelial cells for
      factor VIII. We counted microvessels within the tumors of 42 patients who had
      surgical resection (25 with relapse and 11 without relapse more than 5 years
      after surgical resection). Without knowledge of patient outcome, microvessels
      were counted on a 200x field (0.723 mm2) in the most active areas of
      neovascularization. RESULTS: The microvessel counts from patients with relapse
      after surgical resection (mean +/- standard deviation, 75.4 +/- 64.3) were
      significantly higher than those without relapse more than 5 years after surgical
      resection (42.6 +/- 26.0) (P = 0.027). Analysis of regional lymph node metastases
      (factor N) revealed that the microvessel counts were 62.6 +/- 35.1 for N0 (no
      regional lymph node metastasis), 51.7 +/- 22.2 for N1 (metastasis in ipsilateral,
      peribronchial and/or ipsilateral hilar lymph nodes, including direct extension),
      75.4 +/- 75.3 for N2 (metastasis in ipsilateral mediastinal and/or subcarinal
      lymph nodes), and 74.0 for N3 (metastasis in contralateral mediastinal,
      contralateral hilar, ipsilateral or contralateral scalene or supraclavicular
      lymph node[s]), and these values were not significantly different from each
      other. CONCLUSIONS: Angiogenesis assessed by microvessel counts, correlated
      positively with relapse after surgical resection and hematogenous metastasis in
      all stages of lung adenocarcinoma; there was no correlation with lymph node
      metastasis in lung adenocarcinoma.

PMID- 7522950
TI  - Does transurethral resection of a clinically benign prostate gland increase the
      risk of developing clinical prostate cancer? A 10-year follow-up study.
AB  - BACKGROUND: Theoretical considerations have raised the suspicion that
      transurethral resection of the prostate (TURP) may increase the risk of
      developing prostate cancer in clinically benign prostate glands. Previous studies
      have not shown an increased risk among men who had undergone TURP for benign
      prostatic hyperplasia compared with the risk in age-matched control subjects.
      However, in all of these studies, all men with stage T1 prostate cancer in the
      TURP-group were excluded, possibly creating a bias, because no similar exclusion
      could be made for the controls. METHODS: The incidence and mortality of clinical
      prostate cancer were studied in 198 patients who had TURP and in 203 age-matched
      male control subjects. In both groups, all patients with known prostate cancer
      and patients with suspected cancer by digital rectal examination were excluded
      from the study. However, patients with stage T1 cancer found by the TURP were
      included in the comparison between the groups. RESULTS: The mean age in the two
      groups was 67 +/- 6 years. The patients were followed for an average of 10.2 +/-
      1.2 years and 10.4 +/- 1.8 years in the TURP group and the control group,
      respectively. Clinical prostate cancer developed in six patients who had TURP and
      subsequently in five control (odds ratio, 0.8 [0.2-3.1]; P < 0.97). Before follow
      up, three men in each group died because of prostate cancer (odds ratio, 1.3
      (0.24-7.45); P < 0.97). CONCLUSIONS: The results of this study suggest that
      neither benign prostatic hyperplasia nor TURP increased the risk of developing
      clinical prostate cancer over the next 10 years in patients with a benign
      prostate gland determined by rectal examination before TURP.

PMID- 7522948
TI  - Release of peripheral blood progenitor cells during standard dose
      cyclophosphamide, epidoxorubicin, 5-fluorouracil regimen plus granulocyte colony
      stimulating factor for breast cancer therapy.
AB  - BACKGROUND: High dose chemotherapy with the support of peripheral blood
      progenitor cells (PBPC) is increasingly used in the treatment of solid tumors.
      Although the best method of PBPC mobilization is still under investigation, it
      should be optimized for different tumor types to obtain antitumor effect and
      mobilizing activity. The authors report these results in terms of the number of
      PBPC released and the time of maximum mobilization induced by standard dose
      cyclophosphamide, epidoxorubicin, 5-fluorouracil (CEF) (cyclophosphamide 600
      mg/m2, epidoxorubicin 60 mg/m2, 5-fluorouracil 600 mg/m2) plus granulocyte colony
      stimulating factor (G-CSF) in patients with breast cancer. METHODS: Peripheral
      blood progenitor cells were studied by clonogenic assay of granulocyte macrophage
      colony-forming units (CFU-GM), megakaryocyte colony-forming unit (CFU-Meg) and
      erythrocyte burst-forming unit (BFU-E) and by flow cytometric analysis of CD34+
      cells in 12 patients with early breast cancer throughout three cycles of CEF
      chemotherapy plus G-CSF. RESULTS: Colony assays and CD34+ cell determination were
      performed on 111 and 151 blood samples, respectively. The peak of CFU-GM and
      CD34+ cells occurred consistently at day 11 throughout all three cycles. At day
      11 of the first cycle, the median peak values were 2223 CFU-GM/mL and 256 CD34+
      cells/microL. A progressive decrease in peak value from the first to the third
      cycle was observed. CONCLUSIONS: Standard dose CEF chemotherapy plus G-CSF is a
      disease specific regimen allowing PBPC mobilization without any relevant
      toxicity. Maximum mobilization was recorded at day 11 of the first cycle.

PMID- 7522951
TI  - Vascular patterns of gestational trophoblastic tumors by color Doppler
      ultrasound.
AB  - BACKGROUND: Destruction of uterine vasculature is a common phenomenon in
      gestational trophoblastic tumors. The authors categorized such uterine
      vasculature by color Doppler ultrasound and studied its clinical significance.
      METHODS: Color Doppler ultrasound was performed in 28 patients with gestational
      trophoblastic tumors. The vascular morphologic manifestations were recorded, and
      the peak systolic velocity and resistance index of uterine artery were
      calculated. Serum beta-human chorionic gonadotropin (hCG) levels were measured
      periodically to monitor chemotherapy response. Seventeen uneventful postmole
      uteri were used as controls. Two-tailed Student's t-test and Fisher's exact test
      were used for statistical analysis. RESULTS: The gestational trophoblastic tumors
      were categorized as diffuse type (N = 7), lacunar type (N = 16), and compact type
      (n = 5) according to their vascular patterns. The mean serum beta-hCG level at
      diagnosis in diffuse type lesions (6608 +/- 6320 mIU/mL) was significantly lower
      than in the lacunar type (40462 +/- 39735 mIU/mL; P = 0.04) and compact type
      (212114 +/- 205126 mIU/mL; P = 0.02), whereas the level in compact type lesions
      was significantly higher than in the lacunar type (P = 0.003). Lacunar type
      lesions exhibited a significantly lower uterine artery resistance index (0.51 +/-
      0.13) than diffuse type (0.66 +/- 0.10; P = 0.03) or compact type lesions (0.70
      +/- 0.06; P = 0.02). All lesions exhibited significantly higher peak systolic
      velocity than control subjects (P < 0.001); however, no significant difference
      was observed among them. Brief courses (< 5 cycles) of chemotherapy cured more
      diffuse type (6 of 7) than lacunar type (3 of 15, P = 0.006) or compact type
      lesions (0 of 5, P = 0.008). Histopathologic diagnosis was available for 11
      lesions. They were invasive mole in seven lacunar type lesions and
      choriocarcinoma in four compact type lesions. CONCLUSION: Vascular morphologic
      patterns of gestational trophoblastic tumors by color Doppler ultrasound
      correlated well with beta-hCG levels, uterine hemodynamics, chemotherapy
      response, and possibly the histopathologic diagnosis.

PMID- 7522952
TI  - Identification of bone marrow micrometastases in patients with prostate cancer.
AB  - BACKGROUND: Thirty percent of patients with clinically localized prostate cancer
      and a negative bone scan will experience relapse with recurrent disease despite
      treatment of the primary tumor. This may be due to the presence of metastatic
      prostate cancer cells at the time of treatment undetected by conventional
      methods, radionucleotide bone scan, and serum prostatic specific antigen blood
      test. METHODS: The authors used polymerase chain reaction (PCR) amplification of
      the prostate-specific antigen (PSA) mRNA sequence reverse-transcriptase PCR
      (RTPCR) and immunohistochemistry using a PSA antibody to identify metastatic
      prostate cancer cells in the bone marrow of patients with prostate cancer.
      RESULTS: Micrometastases were found in the bone marrow of 29 of the 55 patients
      (51%) with prostate cancer and in 0 of the 5 patients with benign prostatic
      hyperplasia. Samples from five of the seven patients with lymph node metastases
      and from all five patients with bony metastases contained micrometastases. Of the
      samples taken from 43 patients undergoing radical prostatectomy and with no
      evidence of metastatic disease, 19 (44%) had micrometastases. Four of the 20
      samples (20%) from patients with pathologically localized disease and 15 of the
      23 samples (65%) from patients with extraprostatic disease had micrometastases (P
      = 0.003). Bone marrow slides were available on 24 of the 29 patients who were
      positive for micrometastases by RTPCR: Immunohistochemistry using the PSA
      antibody identified metastatic cells in 19 of these 24 patients. CONCLUSIONS:
      Reverse-transcriptase polymerase chain reaction of bone marrow samples from
      patients with clinically localized prostate cancer may improve the accuracy of
      prostate cancer staging and identify patients at high risk for metastatic
      disease.

PMID- 7522953
TI  - Gonadotropin-releasing hormone receptor in gynecologic tumors. Frequent
      expression in adenocarcinoma histologic types.
AB  - BACKGROUND: Gonadotropin-releasing hormone (Gn-RH) analogs have been used in the
      therapy of the endocrine-dependent cancers. The authors attempted to determine
      the frequency with which Gn-RH receptor (Gn-RHR) is present in gynecological
      cancers. METHODS: Experiments were performed on gynecologic tumors that had been
      surgically removed and their cloned cell lines. Gn-RHR was characterized by
      [3H]Gn-RH binding to plasma membrane preparations. Gn-RHR messenger ribonucleic
      acid was determined by reverse transcription-polymerase chain reaction using
      oligonucleotide primers synthesized according to the published human Gn-RHR
      sequence. RESULTS: High affinity binding sites with nanomolar range of Kd and Gn
      RHR mRNA were detected in a high proportion (over 90%) of the specimens from
      endometrium (6 of 6) and endometrial carcinomas (16 of 17), myometrium (6 of 6)
      and myomas (4 of 5), epithelial carcinoma (21 of 23), and stromal tumors (3 of 3)
      of the ovary. There was no substantial Gn-RHR in cervical carcinomas or germ cell
      derived tumors of the ovary. Cloned cell lines gave identical results to those
      obtained in their respective mother tumors. CONCLUSIONS: We detected Gn-RHR in a
      wide range of the carcinomas and tissues originating from the endometrium and
      ovary, but not in the uterine cervix or germ cell-derived tumors. The expression
      of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory
      role in the growth of these carcinomas, and provides a possible point of attack
      for therapeutic approaches using Gn-RH analogs in these malignancies.

PMID- 7522954
TI  - Independent expression of p55 and p75 interleukin-2 receptors (IL-2R) during
      intravenous or subcutaneous administration of recombinant interleukin-2 (rIL-2)
      by T-lymphocytes and natural killer cells.
AB  - BACKGROUND: The effects of immunotherapy with recombinant interleukin-2 (rIL-2)
      on peripheral blood lymphocytes have been a matter of debate. In this study the
      authors addressed the issue of the biologic effects of two different schedules of
      rIL-2 administration (i.e., continuous intravenous infusion versus subcutaneous
      injection) on the expression of the p55 and p75 chains of interleukin-2 receptor
      (IL-2R). METHODS: Sixteen patients were studied: 6 patients with a previous
      diagnosis of acute leukemia entered the study at least +60 days (+63(-)+144 days)
      after autologous bone marrow transplantation and were treated with continuous rIL
      2 infusion; 10 patients with advanced metastatic renal cancer were treated with
      subcutaneous rIL-2 therapy. In both groups of patients, therapy consisted of two
      cycles of 5-day rIL-2, and immunologic evaluation was performed two days after
      completion of the second cycle. RESULTS: Intravenous treatment was associated
      with a marked increase in CD56+ natural killer (NK) cells expressing the p75 but
      lacking the p55 IL-2R; however, the absolute number of CD3+ lymphocytes was
      unchanged, and they showed a low or absent expression of the p55 and negativity
      for the p75 IL-2R. After subcutaneous rIL-2 therapy, a slight increase in the
      percentage of NK cells expressing only the p75 IL-2R was shown. CD3+ lymphocytes
      still retained the p75 IL-2R negative phenotype, however, with a significant
      increase (> 15%) in p55 IL-2R expression. The absolute number of CD3+ lymphocytes
      was also significantly increased. Functional tests on the purified CD3+
      population indicate that these cells exhibited low values of cytotoxic and
      proliferative activities in vitro. CONCLUSIONS: The authors' data point out that
      subcutaneous administration of rIL-2 during a 2-week period is associated with a
      marked increase in T-cells that bear the low affinity p55 IL-2R. These findings
      could be relevant considering the independent role of lymphokine modulation
      mediated by the p55 and p75 IL-2R on T- and NK cells.

PMID- 7522955
TI  - Expression of galactoside-specific endogenous lectins and their ligands in human
      oral squamous cell carcinoma.
AB  - Human endogenous lectins have a wide spectrum of biological functions. The
      present study analyses the expression of beta-galactoside specific and N-acetyl-D
      galactosamine specific endogenous lectins in oral squamous cell carcinomas using
      biotinylated neoglycoproteins. The expression pattern of beta-galactosyl
      containing glycoconjugates or ligands of beta-galactoside specific lectins in
      these tissues was also studied using an endogenous biotinylated lectin, the human
      14-kDa lectin. For comparison a galactoside specific plant lectin from mistletoe,
      Viscum album was also employed. The results demonstrate that oral squamous cell
      carcinomas mainly express accessible binding sites for lactosylated
      neoglycoprotein (90%) while few carcinomas expressed mild amount of N-acetyl-D
      galactosamine specific binding sites (40%). There was no difference in the
      binding patterns of these probes between well and less differentiated carcinomas.
      Expression of these neoglycoprotein binding sites were mostly concentrated in
      immature basaloid cells, indicating a possible association with cell
      proliferation. The binding pattern of D-galactosyl specific lectins (human 14-kDa
      and mistletoe lectins) showed conspicuous differences. This feature emphasizes
      the caution that needs to be exercised in interpreting the biological
      significance of results attained using plant lectins on human tissue.

PMID- 7522949
TI  - Expression of cytokeratin 10, 13, and involucrin as prognostic factors in low
      stage squamous cell carcinoma of the uterine cervix.
AB  - BACKGROUND: The identification of pretreatment markers with predictive
      significance for the presence of lymph node metastases and treatment outcome in
      low stage cancer of the uterine cervix is clinically important. Because the
      presence of differentiation-related markers varies in this type of cancer, the
      authors investigated whether loss of these markers is related to a poor clinical
      course. METHODS: An indirect immunoperoxidase technique was applied to formalin
      fixed, paraffin embedded tissue sections of 80 patients with International
      Federation of Gynecology and Obstetrics Stage IB and IIA primary squamous cell
      cervical carcinomas for detection of expression of cytokeratin 10 and 13, and
      involucrin. Comparisons were made of the expression of each of these markers
      among 40 patients with regional node metastases and 40 age-matched patients with
      no lymph node metastases. Differences in the frequency of expression of these
      markers also were analyzed in relation to histopathologic characteristics,
      recurrence, and survival. RESULTS: Expression of cytokeratin 10, 13, and
      involucrin was found in 24, 64, and 53%, respectively, of all patients studied.
      The authors found no differences between patients with positive regional lymph
      nodes and those with negative lymph nodes. Expression of cytokeratin 13 and
      involucrin was associated with tumor grade (P = 0.01). No relationship was found
      between expression of the markers used and recurrence or survival in the entire
      group. Within the lymph node-positive group, however, the survival rate of
      patients with tumors with cytokeratin 13 expression was significantly higher than
      that of patients with tumors lacking cytokeratin 13 expression (P = 0.02).
      CONCLUSION: Expression of cytokeratin 10, 13, or involucrin in the primary tumor
      is of no predictive value with respect to the presence of regional lymph node
      metastases in low stage squamous cell cervical cancer. However, cytokeratin 13
      expression appears to be of prognostic significance in patients with positive
      regional lymph nodes.

PMID- 7522956
TI  - Enhanced suppression of tumor growth by combination of angiogenesis inhibitor O
      (chloroacetyl-carbamoyl)fumagillol (TNP-470) and cytotoxic agents in mice.
AB  - The antitumor effect of the novel angiogenesis inhibitor O-(Chloroacetyl
      carbamoyl) fumagillol, TNP-470 (TNP, s.c.), a synthetic analogue of fumagillin,
      was studied in combination with cytotoxic agents--mitomycin C (MMC, i.p.),
      Adriamycin (i.p.), cisplatin (i.p.), and 5-fluorouracil (i.p.), using B16BL6
      melanoma (B16 M) and Lewis lung carcinoma in C57BL/6 mice. When the mice were
      treated on days 3 and 5, addition of MMC (total dose, 5 mg/kg) or 5-fluorouracil
      (140 mg/kg) to TNP (150 mg/kg) maximally reduced s.c. B16 M volume from 60 to 15%
      or from 68 to 40% of control, respectively, and addition of MMC (5 mg/kg) to TNP
      (150 mg/kg) reduced s.c. Lewis lung carcinoma volume from 75 to 62% of control (P
      < 0.02, compared to the corresponding single drug treatments). During treatment
      on days 3, 5, 7, 9, and 11, addition of MMC (5 mg/kg) to TNP (150 mg/kg) reduced
      s.c. B16 M volume from 43 to 6% of control and reduced the number of pulmonary
      metastasis of i.v. B16 M from 26 to 5% of control (P < 0.001). For established
      tumors (> 5 mm in maximal diameter), addition of MMC (12-14 mg/kg), Adriamycin
      (15-17.5 mg/kg), or cisplatin (4 mg/kg, by one shot) to TNP (120-140 mg/kg) with
      a 6-7 fractionated dosing schedule reduced s.c. B16 M volume from 50 to 20, 24,
      or 31% of control and reduced s.c. Lewis lung carcinoma volume from 52 to 34, 27,
      or 34% of control, respectively (P < 0.02). The effect of combination therapy was
      additive and dose-dependent, and the earlier fractionated dosing schedule exerted
      more enhanced antitumor effects. TNP reduced the body weight by approximately 10%
      of control at maximum, but this toxicity was reversible and was not affected by
      addition of the cytotoxic agents. The results suggest that the combination of
      angiogenesis inhibitor TNP and standard cytotoxic agents can be a beneficial
      addition to the treatment of solid tumors.

PMID- 7522957
TI  - Identification of MART-1-specific T-cell receptors: T cells utilizing distinct T
      cell receptor variable and joining regions recognize the same tumor epitope.
AB  - Tumor-specific cytotoxic T lymphocytes (CTLs) can mediate tumor regression in
      patients with metastatic melanoma and play a central role in the immune response
      to cancer. The recent identification of shared melanoma antigens has raised the
      possibility of a limited melanoma-specific T-cell receptor (TCR) repertoire, but
      subsequent studies have been controversial and difficult to interpret without
      knowing which tumor-associated antigens (TAAs) are being recognized by specific
      TCRs. However, the recent cloning of several melanoma TAAs now allows for the
      identification of the specifically recognized TAA and its epitope. We evaluated
      the TCR of two clonal CD8+ CTL lines, A42 and 1E2, from two HLA-A2+ patients with
      metastatic melanoma. Both CTL lines were MART-1 specific, and both demonstrate
      reactivity to the same epitope when presented in an HLA-A2.1 context. The TCR
      genes of the two clones were sequenced. All of the productively rearranged A42
      TCR beta chain genes were V beta 7/D beta 2.1/J beta 2.7/C beta 2; the TCR alpha
      chain genes were V alpha 21/J alpha 42/C alpha. The 1E2 TCR beta chain genes were
      V beta 3/D beta 1.1/J beta 1.1/C beta 1, and TCR alpha chains were V alpha 25/J
      alpha 54/C alpha. This study is the first report of TCR sequences specific for a
      melanoma epitope. These TCR clones may be useful for the development of more
      effective immunotherapies and in studies of the mechanism of T-cell recognition
      of tumor antigen. They also provide direct evidence that the immune system can
      provide more than one TCR capable of recognizing a TAA epitope.

PMID- 7522958
TI  - B7-1/CD80-transduced tumor cells elicit better systemic immunity than wild-type
      tumor cells admixed with Corynebacterium parvum.
AB  - Tumor cells genetically modified by transduction of B7 (B7-1/CD80), a natural
      ligand for the T-cell costimulatory molecules CD28 and CTLA-4, can elicit potent
      tumor immunity, and they can be effective for treatment of established cancers in
      animal models. In this study, three tumor lines, the EL4 lymphoma, the P815
      mastocytoma, and the MCA102 sarcoma were transduced with recombinant retrovirus
      containing the murine B7 gene, and their potency to induce systemic immunity
      protective against challenge with wild-type tumor was compared to that of the
      same tumor cells admixed with the commonly used adjuvant Corynebacterium parvum.
      While admixture of tumor cells with C. parvum resulted in complete regression of
      tumors in syngeneic mice, it did not induce protective immunity against a
      subsequent challenge of wild-type cells from any of the 3 tumors tested. In
      contrast, B7-transduced EL4 and P815 tumors regressed locally and induced a
      potent systemic immunity to wild-type tumors and a higher level of cytotoxic T
      cell activity than did tumor cells admixed with C. parvum. No systemic immunity
      was induced by B7-transduced nonimmunogenic MCA102 sarcoma cells. Our results
      demonstrate that immunogenic tumor cells transduced with the B7 gene are superior
      to tumor cells mixed with C. parvum for the induction of systemic tumor immunity.

PMID- 7522959
TI  - Androgen receptor activation in prostatic tumor cell lines by insulin-like growth
      factor-I, keratinocyte growth factor, and epidermal growth factor.
AB  - Aberrant activation of the androgen receptor (AR) may be one of the mechanisms
      which contribute to progression of prostatic carcinoma to an androgen-independent
      stage. We investigated effects of growth factors on stimulation of the AR
      mediated gene transcription in human prostatic tumor cell lines. DU-145 cells,
      which do not contain endogenous AR, were cotransfected with an androgen-inducible
      chloramphenicol acetyltransferase (CAT) reporter gene and an AR expression
      vector. The reporter gene (CAT) was driven either by artificial promoters
      consisting of one or two androgen-responsive elements in front of a TATA box or
      by the promoter of the prostate-specific antigen (PSA) gene, a naturally
      occurring androgen-inducible promoter. Insulin-like growth factor-I (IGF-I), at a
      concentration of 50 ng/ml, stimulated AR-mediated reporter gene transcription to
      the same extent as the synthetic androgen methyltrienolone. This growth factor
      was effective irrespective of the nature of the androgen-inducible promoter.
      Keratinocyte growth factor (KGF) and epidermal growth factor (EGF), at
      concentrations of 50 ng/ml, activated CAT reporter gene transcription only in
      experiments in which the artificial promoter with two androgen-responsive
      elements was used. Insulin-like growth factor-II and basic fibroblast growth
      factor displayed no effect on AR-mediated gene transcription. None of the growth
      factors stimulated reporter gene activity in control experiments when added to
      cells cotransfected with the CAT gene and an empty expression vector. AR
      activation by IGF-I, KGF, and EGF was completely inhibited by the pure AR
      antagonist casodex, showing that these effects are AR mediated. Activation of
      endogenous AR by growth factors was studied in the LNCaP cell line by
      determination of PSA secretion. IGF-I, at a concentration of 50 ng/ml, increased
      the PSA level in the supernatant of this cell line 5-fold. Again, the IGF-I
      effect on PSA secretion was blocked by casodex. Our results provide evidence that
      IGF-I, KGF, and EGF directly activate the AR in the absence of androgens, which
      means that the androgen-signaling chain may be activated by growth factors in an
      androgen-depleted environment. These findings may have implications for endocrine
      therapy for metastatic prostatic carcinoma.

PMID- 7522960
TI  - Modulation by retinoic acid (RA) of squamous cell differentiation, cellular RA
      binding proteins, and nuclear RA receptors in human head and neck squamous cell
      carcinoma cell lines.
AB  - The ability of all-trans-retinoic acid (RA) to modulate the growth and squamous
      differentiation of four head and neck squamous cell carcinoma cell lines (183,
      886, 1483, and SqCC/Y1) was examined, and the relationship of their state of
      squamous differentiation and RA responsiveness to the expression of cytosolic RA
      binding proteins (CRABPs), nuclear RA receptors (RARs), and retinoid X receptors
      (RXRs) was investigated. RA inhibited proliferation of all but the 183 cell line
      and suppressed squamous differentiation markers K1 keratin, type 1
      transglutaminase, and involucrin mRNAs and proteins to varying degrees in 183,
      1483, and SqCC/Y1 cells. Traces of CRABP-I mRNA were detected only in the 886
      cells, whereas CRABP-II mRNA was detected in the other three cell lines. RA
      suppressed CRABP-II expression in SqCC/Y1 cells but had no effect on its
      expression in the other cell lines. All cell lines expressed mRNAs for RAR-alpha,
      RAR-beta, RAR-gamma, and RXR-alpha. The RAR-beta mRNA level was lowest in the
      SqCC/Y1 cells, and RXR-beta and RXR-gamma were not detected in any of the cell
      lines. RA treatment increased the levels of the three RAR mRNAs in most of the
      cell lines but had no effect on the RXR mRNAs. The CRABP-II mRNA level in SqCC/Y1
      cells was lowest in cells grown in serum-free medium and increased when the cells
      were grown in medium with 5 or 10% serum. In contrast, the RXR-alpha mRNA level
      was inversely related to serum concentration. The results show that, in head and
      neck squamous cell carcinoma cells, there are no simple relationships among the
      expression of CRABPs, RARs, and RXRs and either squamous differentiation or
      response to RA-induced growth inhibition or suppression of squamous
      differentiation.

PMID- 7522961
TI  - Induction of antitumor immunity by recombinant vaccinia viruses expressing B7-1
      or B7-2 costimulatory molecules.
AB  - Activation of T cells requires at least two signals: an antigen-specific signal
      delivered through the T-cell receptor and a costimulatory signal mediated through
      molecules designated B7-1 and B7-2. Previous studies have shown that introduction
      of B7-1 and B7-2 into tumors using retroviral vectors has led to enhanced
      antitumor effects. A limiting factor for potential clinical applications using
      this approach is the low efficiency of infection of retroviral vectors and
      consequent manipulations of infected cells. Vaccinia virus thus represents an
      alternative vector for B7 gene expression in tumor cells. In this report we
      describe the construction and characterization of recombinant vaccinia viruses
      containing the murine B7-1 and B7-2 genes (designated rV-B7-1 and rV-B7-2).
      Infection of BSC-1 cells with these constructs results in rapid and efficient
      cell surface expression of both B7-1 and B7-2 (> 97% of cells at 4 h). Infection
      of murine carcinoma cells with low multiplicity of infection of wild-type
      vaccinia virus leads to the death of the host following tumor transplantation. In
      contrast, inoculation of rV-B7-1- or rV-B7-2-infected tumor cells into
      immunocompetent animals resulted in no tumor growth. These studies demonstrate
      the utility of recombinant vaccinia viruses to deliver B7 molecules to tumor
      cells for potential gene therapy and recombinant approaches to cancer
      immunotherapy.

PMID- 7522962
TI  - Amplification and overexpression of HER-2/neu in carcinomas of the salivary
      gland: correlation with poor prognosis.
AB  - There are few reliable prognostic markers of biological aggressiveness for head
      and neck carcinomas in general. For salivary gland carcinomas, anatomic location,
      tumor size, histological grade, and extent of disease involvement are considered
      to be clinically important risk factors for recurrent disease. Molecular genetic
      alterations in salivary gland carcinomas have not been characterized, and tumor
      cell proteins have not been shown to be prognostically significant. Here a cohort
      of mucoepidermoid carcinomas of the major (parotid and submandibular) salivary
      glands are analyzed for a molecular genetic alteration, HER-2/neu gene
      amplification, and gene amplification and expression results are compared with
      long-term clinical follow-up information. Archival tissues resected from 58
      patients with mucoepidermoid carcinoma of salivary glands were evaluated for HER
      2/neu gene amplification by fluorescence in situ hybridization and for gene
      expression by immunohistochemistry in a blinded fashion. Clinical follow-up
      information was compared with the results of these analyses to determine whether
      there were significant associations. Overexpression, identified as membrane
      immunostaining by immunohistochemistry, was observed in 22 of 58 (38%)
      mucoepidermoid carcinomas. Gene amplification, characterized by fluorescence in
      situ hybridization, was observed in 12 (21%) cases. Eleven of the 12 cases with
      gene amplification were also immunostained for HER-2/neu. Both gene amplification
      (P = 0.0001, P < 0.0001) and immunostaining (P < 0.0001, P < 0.0001) were
      correlated with shorter disease-free interval and poorer overall patient
      survival, respectively. Multivariate analysis showed that HER-2/neu
      immunostaining and amplification were markers of poor prognosis independent of
      histopathological grade, tumor size, and involvement of regional lymph nodes. HER
      2/neu is amplified and/or overexpressed in approximately one-third of
      mucoepidermoid carcinomas of salivary glands. Amplification and/or overexpression
      appears to be an independent marker of poor prognosis in mucoepidermoid
      carcinomas of the salivary glands as it is in carcinomas of the breast, ovary,
      and endometrium.

PMID- 7522965
TI  - Assessment of ability of levcromakalim and sodium nitroprusside to reverse the
      cardiovascular effects of nitric oxide synthase inhibition in the anaesthetised
      pig.
AB  - OBJECTIVE: The aim was to test the ability of levcromakalim, a potassium channel
      opener, and sodium nitroprusside, a nitric oxide donor, to reverse the systemic
      and pulmonary vasoconstrictor actions of NG-nitro-L-arginine methyl ester (L
      NAME), and thus to restore cardiac output in anaesthetised pigs. METHODS: In
      separate groups of pigs administration of a bolus of L-NAME (10 mg.kg-1) was
      followed either by no further agent (control group; n = 8) or by increasing bolus
      doses of levcromakalim (10, 20, and 40 micrograms.kg-1; n = 8) or by increasing
      infused doses of sodium nitroprusside (1, 2, and 4 micrograms.kg-1.min-1 for 15
      min at each dose). The same doses of levcromakalim and sodium nitroprusside were
      also given to pigs (n = 6 in each group) which had been pretreated with saline
      rather than L-NAME. The changes in systemic and pulmonary haemodynamic indices
      and cardiac output as a result of each intervention were measured at each stage
      and compared between and within drug groups. RESULTS: In each group, the bolus of
      L-NAME caused increases in systemic vascular resistance, mean arterial pressure,
      pulmonary vascular resistance, and mean pulmonary artery pressure, and a
      reduction in cardiac output. These effects were significantly different from
      pretreatment values at 15 min, and were maintained for at least 60 min when no
      further agent was given. The subsequent administration of levcromakalim caused
      significant reductions in systemic vascular resistance and mean arterial
      pressure, the effects being greater than in animals that had been pretreated with
      saline rather than L-NAME. Pulmonary vascular resistance and mean pulmonary
      artery pressure were also reduced, but to a lesser degree. Cardiac output was
      partially but significantly restored. The subsequent administration of sodium
      nitroprusside caused significant reductions in systemic vascular resistance, mean
      arterial pressure, pulmonary vascular resistance, and mean pulmonary artery
      pressure. These effects were significantly greater than those in animals that had
      been pretreated with saline rather than L-NAME. Cardiac output was weakly, though
      significantly restored. CONCLUSIONS: Increased systemic vascular resistance
      following a bolus of L-NAME (10 mg.kg-1) is reversed by subsequent administration
      of levcromakalim (10-40 micrograms.kg-1) or sodium nitroprusside (1-4
      micrograms.kg-1.min-1) associated with partial restoration of cardiac output. The
      degree to which cardiac output is restored by these two agents is limited by a
      concomitant reduction in preload.

PMID- 7522964
TI  - Mapping effector functions of a monoclonal antibody to GD3 by characterization of
      a mouse-human chimeric antibody.
AB  - R24, a mouse monoclonal antibody against GD3 ganglioside, exhibits a wide range
      of in vitro effector functions. It also has the ability to bind to itself,
      presumably through homophilic Fab-Fab interactions, which have been proposed to
      contribute to its high relative avidity for GD3 and to its effector function
      activity. It is not known which of these characteristics is necessary for the
      antitumor effects observed in melanoma patients treated with R24. A mouse-human
      chimeric R24 (chR24) molecule has been constructed in which the GD3-binding site
      is preserved. Chimeric R24 demonstrates a lower level of binding to GD3 than does
      mouse R24 suggesting that there may be some differences between the GD3-binding
      sites of the two mAb or that Fc determinants can contribute to R24 avidity for
      GD3. The property of homophilic binding is retained by chR24, demonstrating
      formally that homophilic binding of R24 involves interactions between variable
      domains. Both R24 and chR24 fix human complement and mediate antibody-dependent
      cellular cytotoxicity although chR24 was slightly less efficient at the latter.
      Unlike R24, chR24 was not able to inhibit melanoma cell attachment to plastic
      surfaces and was not able to activate human T lymphocytes. We hypothesize that
      chR24 does not bind to GD3 with an avidity high enough to mediate these effector
      functions.

PMID- 7522966
TI  - Evidence that prostaglandins I2, E2, and D2 may activate ATP sensitive potassium
      channels in the isolated rat heart.
AB  - OBJECTIVE: The aim was to study the contribution of ATP sensitive potassium
      channels (KATP channels) in the coronary vasodilatation produced by
      prostaglandins I2, E2, and D2 in rats. METHODS: Isolated Langendorff rat hearts,
      perfused under constant flow conditions, and rat aortic rings were used. Dose
      response curves to PGE2, PGD2, and iloprost, a PGI2 analogue, were performed
      before and during KATP channel blockade with glibenclamide. Arachidonic acid was
      used to increase the formation of endogenous PGI2. RESULTS: Infusions of PGE2,
      PGD2, and iloprost in isolated hearts induced marked vasodilatation, as reflected
      by the reduction in coronary perfusion pressure of 27(SEM 7), 30(6), and 43(6)%,
      for 0.1 microM PGE2, PGD2, and iloprost, respectively. Infusion of glibenclamide
      (0.3 microM) was accompanied by a 23(3)% increase in coronary perfusion pressure.
      The vasodilatation induced by levcromakalim (0.1 microM) was completely inhibited
      in the presence of glibenclamide, whereas that of papaverine (30 microM) was
      unaffected. Glibenclamide significantly reduced the vasodilatation induced by
      iloprost (at 3 to 100 nM), PGE2 (30 and 100 nM), and PGD2 (30 and 100 nM), at all
      concentrations studied. In contrast, glibenclamide (1 microM) had no effect on
      iloprost induced relaxation of aortic rings. Arachidonic acid infusion (from 0.1
      to 3 microM) in isolated hearts induced a pronounced vasodilatation and a
      significant release of 6-keto-PGF1 alpha into the coronary effluent in a dose
      dependent fashion. Both responses to arachidonic acid were significantly reduced
      in the presence of the cyclo-oxygenase inhibitor diclofenac (1 microM). In an
      additional experimental series, the vasodilatation induced by arachidonic acid
      infusions was found to be significantly reduced in the presence of glibenclamide.
      CONCLUSIONS: Glibenclamide is a potent inhibitor of the coronary dilator action
      of prostaglandins I2, E2, and D2. This observation suggests that these
      prostaglandins may cause vasodilatation by opening KATP channels.

PMID- 7522967
TI  - [Hepatitis C virus infection among the plasmapheresis donors].
AB  - We have made a retrospective study on 621 HBsAg negative plasma donors, 354 HBsAg
      negative non-blood donors, 124 HBsAg positive plasma donors and 124 HBsAg
      positive non-blood donors. Results showed that the respective positive rates of
      anti-HCV were 84.2%, 0.85%, 41.9% and 1.6%, and that the respective prevalence
      rates of viral hepatitis were 34.9%, 1.98%, 18.5% and 4.8%, respectively. These
      figures suggest that HCV infection and the epidemic of hepatitis C mostly occur
      among the plasma donors.

PMID- 7522963
TI  - Comparative study of inhibitory effects by murine interferon gamma and a new
      bisphosphonate (alendronate) in hypercalcemic, nude mice bearing human tumor (LJC
      1-JCK).
AB  - The inhibitory effect of murine interferon gamma (muIFN gamma) on humoral
      hypercalcemia in nude mice bearing lower-jaw cancer (LJC-1-JCK), in which
      parathyroid-hormone(PTH)-related protein is responsible for causing humoral
      hypercalcemia by activating bone resorption, was examined in comparison with that
      of a new bisphosphonate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate
      (alendronate). muIFN gamma was injected into tumor-bearing nude mice for 5 days
      before the establishment of hypercalcemia. The increase of plasma calcium
      concentration was delayed and this effect continued for more than 6 days even
      after the injection was stopped. Alendronate markedly suppressed hypercalcemia in
      tumor-bearing nude mice but this inhibitory effect continued for less than 6
      days. Neither muIFN gamma nor alendronate affected the tumor volume or serum PTH
      related protein concentration. Injection of muIFN gamma into mice for 3 days
      almost completely abolished the formation of multinucleated osteoclast-like cells
      from bone marrow cells in vitro, whereas injection of alendronate into mice had
      no effect. These findings suggested that muIFN gamma suppressed the formation of
      osteoclasts, resulting in the prolonged decrease of plasma calcium concentration
      in hypercalcemic tumor-bearing nude mice, whereas alendronate is cytotoxic to
      functionally mature osteoclasts and inhibited osteoclastic bone resorption,
      resulting in a marked decrease in the plasma calcium concentration in tumor
      bearing hypercalcemic nude mice.

PMID- 7522968
TI  - [Prevalence of HIV and HCV among injecting drug users (IDUs) in Yunnan, China].
AB  - Prevalence of HIV and HCV was studied among 507 IDUs in Yunnan Province. The
      results reveal that sharing needles with other IDUs is one of the primary
      pathways to transmit both HIV and HCV. The rates of HIV and HCV infection in the
      IDU group is 66.5% and 94.9% respectively, which is significantly higher than
      those in the non-IDU group. There is a direct correlation between the rates of
      HIV and HCV antibody positive. 97.5% HCV (+) subjects are also HIV (+); and 57%
      HIV (+) subjects are HCV (+). It is suggested that all IDUs should be encouraged
      to stop using drugs to prevent HIV and HCV transmission.

PMID- 7522969
TI  - Nitric oxide synthases: roles, tolls, and controls.

PMID- 7522970
TI  - Nitric oxide synthase: aspects concerning structure and catalysis.

PMID- 7522971
TI  - Identification and cloning of ELF-1, a developmentally expressed ligand for the
      Mek4 and Sek receptor tyrosine kinases.
AB  - Mek4 and Sek are tyrosine kinases with expression patterns in the mouse embryo
      that suggest important functions in early development. However, like all Eph
      family kinases, both were identified as orphan receptors without known ligands.
      We show that Mek4 and Sek soluble receptor-alkaline phosphatase fusion proteins
      can be used in a procedure termed RAP in situ to identify regions of ligand
      expression in the mouse embryo. Based on this spatial information, a cDNA
      expression library was prepared, and was screened with the fusion proteins to
      identify Eph ligand family-1 (ELF-1). In cell lines and embryos, ELF-1 is
      membrane bound by a phosphatidylinositol tail, a feature that may account for
      unique biological functions. Its sequence is homologous with B61, a ligand for
      the Eck kinase, defining a family of related ligands. The expression domains of
      ELF-1, Mek4 and Sek indicate potential roles in embryonic patterning.

PMID- 7522972
TI  - Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing
      signals override dorsal signals in vivo.
AB  - We report the isolation of a Xenopus BMP receptor that is expressed maternally in
      the appropriate location to play a role in mesoderm induction. This receptor
      binds both BMP-2 and BMP-4 with high affinity. A truncated form of this BMP
      receptor specifically blocks BMP-4 signaling. Expression of this truncated BMP
      receptor during embryogenesis converts ventral mesoderm to dorsal mesoderm.
      Contrary to the popularly held view that ventral is the ground state for all
      mesoderm, our results suggest that formation of ventral mesoderm requires an
      active signal and that, in the absence of this ventral signal, dorsal mesoderm is
      formed.

PMID- 7522975
TI  - Role of LFA-1, CD2, VLA-5/CD29, and CD43 surface receptors in CD4+ T cell
      adhesion to B cells.
AB  - We investigated the adhesion to B cells of CD4+ T cells both in the resting state
      and following activation by CD3 cross-linking or stimulation by
      PMA/ionomycine/IL2 for 6 days. Both resting and activated CD4+ T cell adhesion
      were inhibited by anti-LFA-1, -CD2, -VLA-5/CD29, and -CD43 antibodies, suggesting
      coordinated upregulation of T cell adhesion. The CD2 and LFA-1 adhesion pathways
      were found to act independently, as CD2 was functional in T cells not expressing
      LFA-1, and vice versa, and as specific antibodies had additive effects. In
      contrast, LFA-1- and VLA-5/CD29-specific antibodies did not have an additive
      blocking effect on CD4+ T cell adhesion, suggesting that efficient adhesion
      requires a competitive association of integrins with cytoskeleton elements.
      Although the involvement of fibronectin (coated to B cells via VLA-4) in VLA-5
      mediated T cell adhesion to B cells is feasible, an anti-fibronectin and a VLA-4
      specific antibody had no blocking effect. The involvement of an unidentified B
      cell ligand can also be envisaged.

PMID- 7522974
TI  - A monoclonal antibody (A6) recognizing a unique epitope restricted to CD45RO and
      RB isoforms of the leukocyte common antigen family identifies functional T cell
      subsets.
AB  - The mAb A6 was produced by immunization of mice with human PHA-stimulated PBMC.
      Immunoprecipitation studies and staining of cell lines transfected with
      individual leukocyte common antigen (LCA) isoforms showed that A6 recognizes a
      unique epitope strongly expressed on the lower MW isoform (p180) of LCA, but also
      weakly expressed on the p190 isoform coded by exon B and the p205 coded by exons
      A and B. The epitope recognized by A6 was carbohydrate-dependent in that it was
      neuraminidase-sensitive, but trypsin-resistant. A6 strained most TCR-alpha beta+
      cells with differential intensities, subdividing them into a bright and dim
      population, and strongly stained all TCR-gamma delta+ cells. A6 did not stain
      CD19+ B cells nor CD56+ NK cells. Anti-CD45 mAb such as UCHL1 recognizing CD45RO
      have been used to define memory T cells. Depletion of PBMC subsets with A6 or
      UCHL1 mAb dramatically decreased proliferative responses to the recall antigens
      anti-CD3 mAb and alloantigen and enhanced their responses to PHA. A6, unlike
      UCHL1, also depleted alloreactive T cells that affect primary and secondary MLC
      and CML. Thus, A6 was shown to recognize the lower MW isoforms of LCA which are
      expressed on functional T cell subsets including memory, activated, and
      alloreactive T cells.

PMID- 7522973
TI  - Recruitment of pathogenic T cells to synovial tissues of rats injected
      intraarticularly with nonspecific agents.
AB  - To study a role for T cells in nonspecifically induced arthritis, rats were
      injected intraarticularly into ankle joints with mineral oils including
      2,6,10,15,19,23-hexamethyltetracosane (squalene) and incomplete Freund's
      adjuvant. The results showed that moderate joint inflammation had developed by
      Day 6 after the nonspecific stimulation. This was then followed by induction of
      severe arthritis, reaching a peak on Day 21. Histologically, the early phase of
      arthritis was associated with edema of synovial tissues containing many
      polymorphs and monocytes/macrophages and the late phase of the joint inflammation
      with marked hyperplasia of synovial membrane with dense infiltration of CD5+ and
      alpha beta+ T cells. Depletion of alpha beta+ T cells by a monoclonal antibody
      against TCR alpha beta suppressed both induction and progression of the late
      phase of arthritis. Thus, pathogenic T cells appear to be recruited to joint
      tissues following nonspecific stimulation.

PMID- 7522976
TI  - Induction of membrane ruffling by growth factors in morphologically TPA-resistant
      Balb/c3T3 TR4 cells.
AB  - To investigate the biological characteristics of a Balb/c3T3 variant TR4 clone
      which is morphologically resistant to TPA and hypersensitive to v-src induced
      metastasis, we compared the responsiveness of the variant and its parent cells to
      growth factor-induced membrane ruffling. When the confluent cells were stimulated
      with PDGF, membrane ruffling was rapidly induced in TR4 but not in the parent
      cell cultures. In TR4 cells, membrane ruffling was observed under a phase
      contrast microscope within 2 min after the addition of PDGF, reaching the maximum
      5 min later and thereafter decreased gradually to the control level. There were
      no apparent differences in 125I-PDGF binding kinetics between TR4 and parent
      cells. Similar membrane ruffling was induced by other growth factors such as
      insulin, IGF-I, acidic or basic FGF but not by EGF or alpha- and beta-TGF, only
      in TR4 cells. When TR4 cells were incubated with TPA just before stimulation with
      these growth factors, growth factor-induced membrane ruffling was completely
      inhibited. Also, 5 out of 6 clones of stable fusion cells between TR4 and parent
      cells showed the parental type of responses to TPA and growth factors, indicating
      that the TR4 phenotype is recessive. These results suggest that the variant TR4
      cells may acquire the genetic and recessive alteration of a cellular factor which
      is responsible for the regulation of growth factor-mediated membrane ruffling and
      that this genetic alteration occurs at a common step downstream of growth factor
      mediated cascades, rather than at their receptor level.

PMID- 7522977
TI  - A comparison of pentamorphone and fentanyl in balanced anaesthesia during general
      surgery.
AB  - The purpose of our randomized, double-blind study of 64 unpremedicated healthy
      patients undergoing surgical procedures with a duration of at least 60 min was to
      compare 0.75 micrograms.kg-1 and 1 microgram.kg-1 pentamorphone with 5
      micrograms.kg-1 and 7.5 micrograms.kg-1 fentanyl to determine which dose of
      opioid would reduce the requirement for isoflurane supplementation needed to
      maintain haemodynamic stability. At 21 points during the procedure, the
      haemodynamic variables of heart rate and systolic, diastolic, and mean arterial
      pressures were recorded. The use of isoflurane was quantified; the number of
      patients requiring inhaled anaesthetic, concentration peaks, MAC minutes, and
      duration of isoflurane use were noted. The number of equal-volume supplemental
      opioid analgesic doses, postoperative analgesics, occurrence of postoperative
      nausea, emesis, and antiemetic doses were compared. The four groups exhibited
      similar patient demographics, total dose of muscle relaxants, types of surgical
      procedures, and duration of surgery or anaesthesia. Haemodynamic variables were
      stable with no difference among the four study groups. The patients given
      pentamorphone demonstrated both delayed requirement (P < 0.05) and shorter
      duration (P < 0.05) of isoflurane supplementation. Patients given either 5
      micrograms.kg-1 or 7.5 micrograms.kg-1 fentanyl needed isoflurane supplementation
      within 12 +/- 16 min and 12 +/- 17 min from induction respectively; while
      patients given either 0.75 micrograms.kg-1 or 1 microgram.kg-1 pentamorphone did
      not require isoflurane supplementation for 37 +/- 10 min and 43 +/- 26 min
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522980
TI  - Role of copper accumulation and metallothionein induction in spontaneous liver
      cancer development in LEC rats.
AB  - The LEC rat spontaneously develops liver cancer after suffering chronic liver
      injury caused by abnormal copper accumulation in the liver, but the role of
      copper accumulation in the induction of liver cancer remains obscure. We
      histochemically and biochemically examined the content of copper and
      metallothionein (MT), a cytoplasmic copper binding protein, in spontaneously
      developed preneoplastic and neoplastic liver lesions and compared them with those
      in the surrounding liver tissues. Histochemically, the majority of the
      preneoplastic liver lesions (68%) and liver cancers (59%) showed lower copper
      contents than the surrounding liver tissues and no lesions were shown to
      accumulate more copper than the surrounding tissues. A marked heterogeneity in
      copper staining was observed in cancer tissues. In contrast, these lesions showed
      an equal to higher MT content than their surroundings. Biochemical measurements
      of copper and MT in cancer tissues supported the histochemical findings. The
      bromodeoxyuridine (BrdU) labeling index was high in all cancer tissues and some
      of the preneoplastic liver lesions. Parts of the cancer tissues with negative or
      weak staining for copper were highly labeled with BrdU. Taking these results
      together, copper accumulation may exert a growth inhibitory effect on surrounding
      hepatocytes, whereas the hepatocytes in the liver lesions could proliferate,
      escaping from the effect of copper toxicity by increasing their MT induction and
      lowering copper accumulation. Thus, accumulation of copper may act as a promoting
      factor for the development of liver cancer in LEC rats by creating a selective
      growth environment.

PMID- 7522981
TI  - Growth characteristics and Ha-ras mutations of cell cultures isolated from
      chemically induced mouse liver tumours.
AB  - Cells have been isolated from liver tumours that have arisen in control C3H/He
      mice, in mice given 10 micrograms diethylnitrosamine (DEN) during the neonatal
      period or in mice given a diet containing phenobarbitone (PB) to allow a daily
      intake of 85 mg/kg/day. The cells were grown to the 8 degrees subculture when
      their growth characteristics were investigated in monolayer culture and following
      suspension in soft agar and on transplantation into nude mice. In addition, DNA
      was isolated from the cultures and from tumours that grew in nude mice and
      analysed for mutations at codon 61 of the Ha-ras oncogene. All cells derived from
      DEN-induced hepatocellular carcinomas (HCC) demonstrated a lack of density
      inhibition of growth in monolayer culture, grew in soft agar and formed tumours
      in nude mice with an average mean latency of 29 days. Three of the seven lines
      showed mutations in Ha-ras: two were CAA-->AAA transversions and one showed a CAA
      ->CTA transversion. In contrast, cells isolated from eosinophilic nodules in mice
      given PB showed inhibition of growth at confluence, did not grow in soft agar and
      only four of eight formed tumours in nude mice with a mean average latent period
      of 181 days. Cells grown from HCC in mice given PB showed a lack of density
      inhibition of growth, however, they did not grow in soft agar nor did they form
      tumours in nude mice. A single spontaneous HCC from a control mouse showed a
      similar growth pattern to HCC cells isolated from mice given PB. Cells from a
      basophilic nodule, taken from a control untreated mouse grew vigorously in
      culture and in soft agar and formed tumours in nude mice with a latency of 6
      days. None of the cells isolated from control mice or from mice given PB showed
      evidence of mutations at codon 61 of Ha-ras. These data confirm that there are
      fundamental differences in the biology of cells grown from tumours that develop
      in mice under different treatment regimes. These studies also demonstrate the
      utility of cell culture and molecular biology in addressing the fundamental
      mechanism of mouse hepatic neoplasia.

PMID- 7522978
TI  - Intracellular metabolism of 5-methyltetrahydrofolate and 5-formyltetrahydrofolate
      in a human breast-cancer cell line.
AB  - This report describes the intracellular metabolism of 5-methyltetrahydrofolate (5
      methyl-H4PteGlu) and 5-formyltetrahydrofolate (5-formyl-H4PteGlu) to the various
      folate forms and their respective polyglutamated states in the MCF-7 human breast
      cancer cell line. The intracellular folate distribution observed in MCF-7 cells
      treated with 5-methyl-H4PteGlu was similar to that seen in cells treated with 5
      formyl-H4PteGlu. In cells exposed to 5-formyl-H4PteGlu for 24 h, the folate pool
      consisted of 103 +/- 10 pmol/mg 10-formyl-H4PteGlu, 120 +/- 18 pmol/mg H4PteGlu,
      and 71 +/- 18 pmol/mg 5-methyl-H4PteGlu versus 88 +/- 5, 54 +/- 20 and 87 +/- 10
      pmol/mg, respectively, for cells exposed to 5-methyl-H4PteGlu. Only the
      difference seen in H4PteGlu levels between cells exposed to either 5-methyl
      H4PteGlu or 5-formyl-H4PteGlu reached statistical significance (P < 0.05). In the
      absence of vitamin B12, exposure to 5-methyl-H4PteGlu resulted in 154 +/- 17
      pmol/mg 5-methyl-H4PteGlu along with only 8 +/- 5 pmol/mg 10-formyl-H4PteGlu and
      4 +/- 2 pmol/mg H4PteGlu, thus demonstrating the marked dependence on vitamin B12
      for the metabolism of 5-methyl-H4PteGlu to the other intracellular folates. 5-10
      Methylene- H4PteGlu (2 +/- 1.3 pmol/mg) was detected only in cells exposed to 5
      formyl-H4PteGlu for 24 h, not in cells treated with 5-methyl-H4PteGlu. The
      profile of polyglutamates detected in cells treated with either 5-formyl-H4PteGlu
      or 5-methyl-H4PteGlu for 24 h was not significantly different, although cells
      treated with 5-methyl-H4PteGlu tended to have less conversion to the higher
      polyglutamates (Glu3-Glu5) as compared with those treated with 5-formyl-H4PteGlu.
      In 5-methyl-H4PteGlu-treated cells grown in the absence of vitamin B12, the
      pentaglutamate was the only polyglutamate form detected, accounting for only 11%
      of the total folate pool. Since there does not appear to be a greater formation
      of the optimal reduced-folate forms necessary to achieve enhanced thymidylate
      synthase (TS) inhibition through ternary-complex formation in cells exposed to 5
      methyl-H4PteGlu versus 5-formyl-H4PteGlu, these studies suggest that the use of 5
      methyl-H4PteGlu would not be advantageous over that of 5-formyl-H4PteGlu in
      combination regimens with the fluoropyrimidines.

PMID- 7522979
TI  - Enhancement of liver cell gap junction protein expression by glucocorticoids.
AB  - Gap junctional intercellular communication (GJIC) and the expression of gap
      junction proteins (connexins) may be involved in growth regulation and neoplastic
      transformation. The mechanisms of connexin gene regulation in normal and
      neoplastic tissues are poorly understood. In this study, the glucocorticoids,
      dexamethasone and hydrocortisone, enhanced fluorescent dye-coupling in primary
      cultured rat hepatocytes and MH1C1 rat hepatoma cells. Other types of steroids
      (beta-estradiol, testosterone, aldosterone and progesterone) had no effect.
      Northern blot, Western blot, nuclear run-on and immunohistochemical analyses
      showed that glucocorticoids enhanced the expression of connexin32 in these cells
      in a dose- and time-dependent fashion. Connexin26 expression was also enhanced
      slightly by dexamethasone in hepatocytes, but not MH1C1 cells. Connexin43
      expression in these cells was not affected by steroids. In WB-F344 rat liver
      epithelial cells, which were highly coupled and expressed high levels of
      connexin43 and no detectable connexin32 or connexin26, dexamethasone had no
      effect on coupling or connexin expression. These results indicate that dye
      coupling and the expression of connexin32 and connexin26, but not connexin43,
      were upregulated by glucocorticoids in a cell-specific manner. These effects on
      GJIC and connexin expression may be involved in the induction of hepatic
      differentiation and inhibition of growth.

PMID- 7522982
TI  - Modulation of phenobarbitone-induced loss of gap junctional intercellular
      communication in hepatocyte couplets.
AB  - Phenobarbitone (PB) produced a dose- and time-dependent decrease in gap
      junctional intercellular communication (GJIC) (up to 25.0 +/- 5.3% inhibition) in
      rat hepatocyte couplets (4 h cultures). The effect was reversible and independent
      of protein synthesis. This inhibition was exacerbated (to 53.3 +/- 5.4%
      inhibition) by depletion of intracellular glutathione following pretreatment with
      diethylmaleate (0.5 microM, 15 min). Inhibition was also significantly enhanced
      by addition of the cytochrome P450 inhibitors SKF 525A (25 microM) and metyrapone
      (20 nM). In contrast, hepatocyte couplets derived from rats pretreated with PB
      (0.1% w/v in drinking water) for up to 28 days were fully functional regarding
      GJIC and were found to be refractory to the effects of PB added in vitro. This,
      coupled with the lack of effect of p-hydroxy-PB, suggests that an active
      metabolite of PB is not involved in the inhibition of GJIC which may, instead, be
      through an oxidative stress, which is prevented by glutathione.

PMID- 7522983
TI  - SENCAR mouse skin tumors produced by promotion alone have A to G mutations in
      codon 61 of the c-rasHa gene.
AB  - SENCAR mice, developed by selective breeding for high susceptibility to skin
      carcinogenesis by initiation with 7,12-dimethylbenz[a]anthracene and promotion
      with 12-O-tetradecanoylphorbol-13-acetate (TPA), form squamous papillomas in
      approximately 20% of animals treated repeatedly with TPA, without chemical
      initiation. DNA from eight skin tumors produced by a TPA-only protocol and four
      cell lines derived from these tumors was amplified by polymerase chain reaction
      and analyzed by discriminative oligonucleotide hybridization using oligomers
      specific for various c-rasHa gene codon 61 sequences. Five tumors and three cell
      lines had CAA (wild-type) to CGA mutations. In addition, one tumor had a CAA to
      CTA mutation, for a total of six of eight tumors having an activating mutation at
      this codon. Two tumors and one cell line had no codon 61 mutations detectable by
      this method. Since tumors derived from promotion-only protocols presumably
      originated from constitutively initiated cells, we examined tumor-free skins of
      untreated newborn and eight-month-old retired breeders and of 78-88-week-old
      SENCAR mice of both sexes, which were treated with TPA for 10 weeks starting at
      age 16-28 weeks and were untreated thereafter. Only the wild-type c-rasHa gene
      codon 61 sequence was seen, suggesting that the constitutively initiated cell
      population, if present, is below the limit of detection by this method.

PMID- 7522984
TI  - Carcinogenicity of a mutagenic compound from food, 2-amino-3-methyl-9H-pyrido[2,3
      b]indole (MeA alpha C), in male F344 rats.
AB  - Carcinogenicity of 2-amino-3-methyl-9H-pyrido[2,3-b]-indole (MeA alpha C) was
      investigated at dietary levels of 0 (control), 0.01, 0.02, 0.04 and 0.08% using
      male F344/DuCrj rats. The administration of MeA alpha C was continued for 100
      experimental weeks for the control, 0.01 and 0.02% groups, but halted after 52
      and 26 experimental weeks for the 0.04 and 0.08% groups respectively due to
      severe toxicity. Well-differentiated hepatocellular carcinomas, lacking in
      control animals, were induced in 5/20 rats (25%) and 6/20 rats (30%) of the 0.01%
      and 0.02% groups respectively. Pancreatic acinar cell adenomas were also
      significantly increased in the 0.01% (30%) and 0.02% (40%) groups, in association
      with high incidences of hyperplastic lesions of acinar cells. Fibromas in the
      subcutis developed at a high incidence (70%) in the 0.02% group. MeA alpha C was
      also suggested to elicit fibrosarcomas in the salivary gland and transitional
      cell carcinomas in the urinary bladder. Among the non-neoplastic lesions, severe
      atrophy of the salivary glands and pancreas and severe renal toxicity were
      noteworthy. In conclusion, MeA alpha C is a multi-targeting carcinogen in rats,
      similar in this respect to other heterocyclic amines.

PMID- 7522985
TI  - Immunocytochemical identification of DNA adducts, O6-methylguanine and 7
      methylguanine, in respiratory and other tissues of rat, mouse and Syrian hamster
      exposed to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
AB  - The present paper reports about an immunocytochemical inventory of the cell types
      involved in the metabolic activation of the tobacco-specific nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to a DNA methylating
      metabolite. The formation and distribution of the methylated DNA bases O6
      methylguanine (O6-meGua) and 7-methylguanine (7-MeGua) were studied in
      respiratory tissues, oesophagus, liver, kidneys, pancreas, small intestine, colon
      and prostate of rat, mouse and hamster 6 h after treatment with a single dose of
      30 mg NNK/kg. The tissue- and cell-specific distribution of O6-meGua- and 7-meGua
      specific nuclear staining showed the same patterns and were remarkably similar in
      rat, mouse and hamster in spite of the diverging spectra of NNK-induced tumours
      in these species. In nasal tissue, a target for NNK-induced tumourigenesis in rat
      and hamster, but not in mouse, adduct-specific nuclear staining was observed in
      all three species in sustentacular cells, Bowman glands, respiratory epithelial
      cells and serous glands. Both methylated DNA bases were also observed in basal
      cells of the olfactory epithelium of rat and (occasionally) hamster, but not in
      those of the mouse. In the trachea, a target for NNK-induced tumourigenesis in
      hamster only, substantial adduct-specific nuclear staining was found in basal
      epithelial and glandular cells of the hamster; in the same cells of rat and mouse
      only a weak nuclear staining was found. In the lung, a common target for NNK
      induced tumourigenesis, the formation of O6-meGua and 7-meGua was restricted
      predominantly to bronchial and proximal bronchiolar epithelium. Nuclear staining
      in the rat was occasionally found in alveolar cells and was also observed in
      hepatocytes. In the three species investigated, O6-meGua- and 7-MeGua-specific
      nuclear staining was found in target and non-target tissues. Apparently, and in
      analogy with results obtained in other studies, the species-specific organotropy
      for tumour formation of NNK is not exclusively determined by DNA methylation.
      Expanding methylation data with literature data on factors considered to be
      involved in tumour formation, namely proliferation, toxicity and DNA repair among
      others, still did not lead to a satisfactory explanation for the species-specific
      organotropy observed. Additional factors (yet to be identified), need to be taken
      into account in order to explain (and predict) tumourigenic effects induced by
      monofunctional methylating agents.

PMID- 7522986
TI  - Ellagic acid induces NAD(P)H:quinone reductase through activation of the
      antioxidant responsive element of the rat NAD(P)H:quinone reductase gene.
AB  - Induction of cellular detoxification enzymes can increase detoxification of
      carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis. To
      determine if the dietary anticarcinogen ellagic acid induced enzymes which
      detoxify xenobiotics and carcinogens, we examined the effect of ellagic acid on
      the expression of the phase II detoxification enzyme NAD(P)H:quinone reductase
      (QR). QR is induced by xenobiotics and antioxidants interacting with the
      xenobiotic responsive and antioxidant responsive elements of the 5' regulatory
      region of the QR gene. Ellagic acid is structurally related to the antioxidants
      which induce QR and we proposed that ellagic acid would induce QR expression
      through activation of the antioxidant responsive element of the QR gene. Rats fed
      ellagic acid demonstrated a 9-fold increase in hepatic and a 2-fold increase in
      pulmonary QR activity, associated with an 8-fold increase in hepatic QR mRNA. To
      determine if this increase in QR mRNA was due to activation of the antioxidant
      responsive element, transient transfection studies were performed with plasmid
      constructs containing various portions of the 5' regulatory region of the rat QR
      gene. These transfection studies confirmed that ellagic acid induces
      transcription of the QR gene and demonstrated that this induction is mediated
      through the antioxidant responsive element of the QR gene.

PMID- 7522987
TI  - Different electrical responses to vasoactive agonists in morphologically distinct
      smooth muscle cell types.
AB  - Vascular smooth muscle cells (SMCs) in the blood vessel wall are frequently
      heterogeneous in nature, differing in their gross morphology, size, and shape,
      subcellular organelles, cytoskeleton, and contractile protein composition. In
      adult rat arterial vessels, two populations of SMCs have been shown to
      predominate: elongated bipolar cells, representing the majority of cells, and
      epithelial-like SMCs. We examined the ionic responses of these two types of SMCs,
      isolated by multiple subculture, to vasoactive stimuli. Elevations in
      intracellular Na+ and Ca2+ were measured with SBFI and fura 2, respectively, and
      changes in membrane potential were measured using the potential-sensitive
      fluorescent probe bis-oxonol. The resting membrane potential of the elongated
      bipolar cells was less negative than that of the epithelial-like SMCs. Exposure
      of the elongated SMCs to endothelin 1, alpha-thrombin, or arginine vasopressin
      induced elevations in [Ca2+]i and [Na+]i and membrane depolarization.
      Depolarization occurred because of entry of both Na+ and Ca2+, and
      pharmacological blockade of Cl- or K+ channels did not attenuate the
      depolarization. In contrast, when [Ca2+]i was elevated by the same agonists in
      the epithelial-like SMCs there was a pronounced hyperpolarization that appeared
      to be the consequence of enhanced activity of charybdotoxin-sensitive Ca(2+)
      activated K+ channels because it was abolished by charybdotoxin (20 nmol/L),
      partially attenuated by tetraethylammonium chloride (10 mmol/L), and unaffected
      by apamin (1 mumol/L), glibenclamide (1 mumol/L), or 4-aminopyridine (5 mmol/L).
      Chelation of [Ca2+]i also abolished the hyperpolarization; instead, a small
      depolarization was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522988
TI  - Nonadrenergic noncholinergic nerves regulate basal coronary flow via release of
      capsaicin-sensitive neuropeptides in the rat heart.
AB  - Nonadrenergic noncholinergic nerve fibers supposedly modulate basal coronary flow
      by releasing capsaicin-sensitive neuropeptides, but the physiological effects of
      this intrinsic action have not been clarified. We investigated the intrinsic
      function of nonadrenergic noncholinergic innervation in modulating basal coronary
      flow in rats. We administered capsaicin to 44 rats to deplete neuropeptides such
      as calcitonin gene-related peptide (CGRP) and substance P and administered inert
      vehicle to 60 control rats. Four days later, we measured the coronary pressure
      flow relation in the basal state and during maximal coronary vasodilation induced
      by intracoronary adenosine administration using Langendorff's method. Changes in
      basal coronary flow prompted by intracoronary infusion of CGRP or substance P and
      their antagonists were measured in 54 and 30 rats, respectively. Capsaicin
      treated rats showed a 31.5 +/- 0.9% (mean +/- SEM) reduction (P < .01) of basal
      coronary flow in the range of perfusion pressures between 60 and 140 mm Hg
      compared with untreated control rats, but the maximal coronary flow after
      adenosine was similar between the two groups. Although basal coronary flow was
      reduced in capsaicin-treated hearts, left ventricular contractile force and
      myocardial oxygen consumption did not fall significantly. CGRP increased the
      coronary flow, but substance P did not. CGRP(8-37), a CGRP receptor antagonist,
      reduced basal coronary flow by 24.5 +/- 2.1% (P < .01), but FK888, a substance P
      antagonist, had little effect on it. Thus, capsaicin-sensitive neuropeptides in
      the rat heart modulate basal coronary flow, providing approximately 30% of
      it.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7522994
TI  - [Substance P is not involved in SII descending modulation of the nucleus centrum
      medianum of the thalamus in cats].
AB  - It was investigated that the effects of electrical stimulation of the
      somatosensory area II (SII) of the cerebral cortex and electroacupuncture on
      substance P (SP) concentration in the perfusate from the nucleus centrum medianum
      (CM) of the thalamus, in order to probe into if SP participates in the SII
      descending modulation of the nucleus CM and this mechanism of acupuncture
      analgesia. Adult cats were randomly divided into three groups: control,
      electroacupuncture and electrical stimulation of SII. Push-pull perfusion
      technique was used to collect the perfusate from the nucleus CM. SP contents in
      the perfusate were determined by radioimmunoassay. The results showed that SP
      contents in the perfusate have not statistically significant changes before and
      after the electrical stimulation of SII or electroacupuncture, suggesting that
      the SP release from the nucleus CM was not influenced by the stimulation of SII
      or electroacupuncture. It is indicated that SP may not associate with the SII
      descending modulation of the nucleus CM and this mechanism of acupuncture
      analgesia.

PMID- 7522989
TI  - The anti-inflammatory agent alpha-trinositol exerts its edema-preventing effects
      through modulation of beta 1 integrin function.
AB  - Edema formation in acute inflammation can be induced through lowering of
      interstitial fluid pressure (Pif) and seems to involve dynamic beta 1 integrin
      mediated interactions between dermal cells and extracellular matrix fibers. The
      present experiments investigate the role of beta 1 integrins in the control of
      Pif. The anti-inflammatory drug alpha-trinositol (1,2,6-D-myo-inositol
      trisphosphate) stabilizes Pif in acute inflammation. Pretreatment with 5 mg IV
      alpha-trinositol in pentobarbital-anesthetized rats inhibited the lowering in Pif
      and the edema formation induced by subdermal injection of anti-beta 1 integrin
      IgG. This stabilization of the beta 1 integrin function in vivo was paralleled by
      effects of alpha-trinositol on contraction of fibroblast-populated three
      dimensional collagen lattices in vitro. alpha-Trinositol was additive to the
      known stimulatory effect of platelet-derived growth factor-BB on the final gel
      size in the collagen gel contraction assay. Furthermore, alpha-trinositol
      counteracted the inhibitory effect of anti-beta 1 integrin Fab fragments on
      collagen gel contraction. Finally, subdermal injection of dibutyryl-cAMP (db
      cAMP) induced increased negativity of Pif to the same extent as did anti-beta 1
      integrin antibodies, and in vitro db-cAMP reduced the ability of fibroblasts to
      contract collagen gels. The latter effect was opposed by alpha-trinositol. The
      data demonstrate that alpha-trinositol modulates beta 1 integrin function and may
      do so via intracellular pathways in turn affecting the function and/or cell
      surface expression of beta 1 integrins and suggest that alpha-trinositol can
      serve as a tool to study integrin function. Furthermore, the data indicate that
      the collagen contraction assays may provide important information of the control
      of Pif in vivo.

PMID- 7522993
TI  - [Relationship between the presynaptic depolarization effect of acupuncture and r
      aminobutyric acid, opioid peptide and substance P].
AB  - The present study was performed on 22 cats to explore whether r-aminobutyric acid
      (GABA), endogenous opioid peptide and substance P (SP) were involved in the
      regulation of presynaptic inhibition in acupuncture analgesia. The size of the
      antidromic compound C action potentials of the sural nerve evoked by the testing
      stimulation in spinal cord was measured as an indicator of C-afferent terminal
      excitability. It was found that the electro-acupuncture (EA) at "Huantiao" (GB30)
      and "Yang lingquan" (GB34) points induced significant enlargement of the
      antidromic C-waves, showing the depolarization of presynaptic terminals of
      primary C-afferents was enhanced. The depolarization effect of EA was
      significantly reduced by bicuculline, naloxone and the antiserum of SP locally
      applied to the surface of spinal cord respectively. It is supposed that GABA,
      endogenous opioid peptide and SP may be involved in the regulation of presynaptic
      inhibition in acupuncture analgesia.

PMID- 7522990
TI  - Characterization of the excitable gap in a functionally determined reentrant
      circuit. Studies in the sterile pericarditis model of atrial flutter.
AB  - BACKGROUND: Single premature beats were introduced in the reentrant circuit
      during stable atrial flutter in the canine sterile pericarditis model to test the
      hypotheses that (1) despite the fact that the reentrant circuit is functionally
      determined, there is a fully excitable gap; (2) the excitable gap in the
      reentrant circuit is not uniform; and (3) inhomogeneities of conduction in the
      reentrant circuit explain the effects of premature beats. METHODS AND RESULTS: A
      multiplexing system was used to record 190 unipolar electrograms from the right
      atrial free wall during 18 atrial flutter episodes in 9 dogs. In all 18 episodes,
      premature stimuli captured the atrial flutter reentrant circuit. At the longest
      coupling intervals, the return cycle at the site closest to the pacing site did
      not prolong. As the coupling interval of the premature stimulus decreased, the
      return cycle then progressively increased, associated with changes in conduction
      in the reentrant circuit that were not uniform. The result was that coupling
      intervals associated with introduction of the premature beat also were not
      constant. The mean duration of the total (ie, fully plus partially) excitable gap
      was 12 +/- 4 ms in areas of slow conduction, and it was always shorter than the
      total excitable gap in other areas (22 +/- 6 ms, P < .001). The mean duration of
      the fully excitable gap based on analysis of the return cycle was 4 +/- 1 ms in
      the reentrant circuit. In 13 of 18 atrial flutter episodes, a premature stimulus
      terminated atrial flutter by causing block of the orthodromic wave front of the
      premature beat in an area of slow conduction. The mean coupling interval that
      caused orthodromic block was 113 +/- 5 ms (recorded at the site just proximal to
      the area of block), and it was always longer than the delivered stimulus coupling
      interval at the pacing site (96 +/- 8 ms, P < .001). CONCLUSIONS: We conclude
      that in this functionally determined atrial flutter reentrant circuit in the
      canine sterile pericarditis model, (1) a fully excitable gap is present in at
      least part of the reentrant circuit; (2) the duration of the excitable gap in the
      reentrant circuit is shortest in areas of slow conduction; and (3) when a
      premature beat encounters the partially excitable gap of the reentrant circuit,
      it results in changes in conduction such that the coupling intervals are not
      uniform throughout in the reentrant circuit.

PMID- 7522991
TI  - Initiation of ventricular extrasystoles by myocardial stretch in chronically
      dilated and failing canine left ventricle.
AB  - BACKGROUND: Stretch-induced arrhythmias (SIAs) can be elicited in normal canine
      left ventricles by transient diastolic dilatation. Since clinically important
      ventricular arrhythmias arise most commonly in failing and dilated ventricles, we
      hypothesized that the arrhythmogenic effect of transient diastolic stretch would
      be enhanced in chronically dilated failing canine hearts. METHODS AND RESULTS:
      Heart failure was induced in seven dogs by right ventricular pacing at 250 min-1
      for 20.2 +/- 1.6 days. Left ventricular (LV) mechanical properties were measured
      in vivo with serial echocardiograms in these seven dogs with the dogs awake and
      tranquilized to confirm the development of LV dilation and failure. By the third
      week of pacing, average short-axis area ejection fraction decreased by 64.3% (P <
      .001) as end-diastolic and end-systolic diameters increased by 25.9% and 50.7%,
      respectively (P < .001). After heart failure was established, the hearts were
      harvested and in vitro data were obtained as an isolated, blood-perfused
      ventricle preparation. A computerized servo pump system connected to an LV
      intracavitary balloon was used to measure and control LV volume. Results were
      compared with in vitro data obtained from eight ventricles not subjected to
      pacing (controls). LV contractility, quantitated in vitro as the slope of the
      peak isovolumic pressure-volume relation (Emax) normalized to LV cavity size, was
      much lower in the heart failure group than in controls (182 +/- 18 versus 365 +/-
      38 mm Hg, P < .001). In all isolated hearts, SIAs were induced using an
      electromechanical stimulation protocol in which eight paced beats at 2 Hz were
      followed by a transient increase in LV volume during early diastole. Prestretch
      volume (Vi) was selected to yield end-diastolic pressures of 4 to 8 mm Hg in all
      hearts. The fractional increase in LV volume (delta V) that produced SIAs 50% of
      the time (delta V 50/Vi) was smaller in failing hearts than in controls (0.78 +/-
      0.04 versus 1.18 +/- 0.17, P = .009), indicating an increased sensitivity to SIAs
      in the failing hearts. Although ventricular pairs were occasionally induced in
      both groups, the great majority of the arrhythmias induced in both groups were
      single extrasystoles, and nonsustained runs of ventricular tachycardia were never
      elicited in either group. LV end-diastolic and peak stretch pressures were
      similar in the two groups, but LV end-diastolic wall stress was higher by 35.7%
      (P = .029) in the dilated failing ventricles because LV hypertrophy, which tends
      to normalize wall stress as the heart dilates, did not occur during the 3 weeks
      of pacing. For stretch stimuli of comparable arrhythmogenic effectiveness, peak
      LV wall stress during stretch was similar in the two groups, whereas the
      fractional increase in volume was significantly smaller in the heart failure
      group, indicating impaired viscoelastic properties in the failing ventricles. In
      five control ventricles, acute exposure to 0.5 mumol/L dobutamine increased
      ventricular sensitivity to the induction of SIAs, as shown by a decrease in delta
      V50/Vi from 1.27 +/- 0.16 to 1.06 +/- 0.11 (P = .04). CONCLUSIONS: Altered
      mechanical properties and/or neurohumoral adaptations associated with chronic
      dilation and failure predispose the ventricle to induction of ventricular
      extrasystoles by transient LV diastolic stretch.

PMID- 7522995
TI  - [The role of substance P and somatostatin in acupuncture and moxibustion-induced
      postsynaptic inhibition].
AB  - AIM OF INVESTIGATION: Our previous work indicated that acupuncture and
      moxibustion (heating acupoints with a special lamp) could produce inhibitory
      effects on the tail flick reflex and the nociceptive response of dorsal horn
      neurons. In the present study the role of somatostatin (SS) and substance P (SP)
      in acupuncture and moxibustion-induced postsynaptic inhibition was further
      investigated. METHODS: The experiments were performed on male adult Wistar rats.
      The antidromic action potential (AAP) induced by cervical cord stimulation was
      extracellulary recorded at lumbar cord (L3-4). The latency of AAP was used to
      represent the excitability of postsynaptic projecting neurons. The effects of
      acupuncture (0.5 ms, 3.3 Hz, 2 mA) for five minutes or moxibustion (the
      temperature up to 45-46 degrees C) for six minutes at Huantiao points on the
      latency of AAP were observed. And then the effects of topical administration of
      SS or SP antiserum on either acupuncture or moxibustion-induced postsynaptic
      inhibition were observed. RESULTS: The latency of AAP was markedly prolonged by
      acupuncture and moxibustion. The maximal prolongation was 0.196 +/- 0.071 ms (n =
      12, P < 0.02) and 0.176 +/- 0.062 ms (n = 11, P < 0.02) respectively. After
      topical administration of SS antiserum (1:40, 10 microliters), the latency of AAP
      was slightly prolonged by either acupuncture or moxibustion. The maximal
      prolongation (0.041 +/- 0.029 ms and 0.016 +/- 0.020 ms) was significantly
      reduced by SS antiserum (P < 0.05). While pretreated with SP antiserum, the
      latency was still prolonged by moxibustion (0.142 +/- 0.067 ms), but not by
      acupuncture (-0.003 +/- 0.046 ms). CONCLUSION: It is referred that postsynaptic
      inhibition may be involved in both acupuncture analgesia and moxibustion
      analgesia. The former is predominately mediated by SP and partially by SS, while
      the latter mainly by SS but not by SP.

PMID- 7522992
TI  - [Relationship between acupuncture analgesia and neurotransmitters in nucleus
      raphe magnus].
AB  - Nucleus Raphe Magnus (NRM) is a complex cell group. 5-HT, SP and ENK neurons in
      the NRM were identified by immunocytochemistry method. The afferent fibers
      containing 5-HT, SP, M-ENK, L-ENK, B-EP and SRIF were observed in NRM, the
      efferent fibers containing 5-HT, SP, ENK and TRH from NRM to spinal cord were
      studied. Two neurotransmitters (such as 5-HT with SP, ENK or TRH) were found in
      same neuron, fiber or vesicle. The neurons and axo-dendritic synapses of the NRM
      were analysed during Electroacupuncture (EA). The NRM increased their synaptic
      releases and the neurons were in active functional state during EA "Zusnanli".
      Studies show that NRM is one of important positions in EA analgesia.

PMID- 7522996
TI  - An improved method for quantification of very long chain fatty acids in plasma.
AB  - Most peroxisomal disorders can be detected via analysis of very long chain fatty
      acids (VLCFA) and phytanic acid in plasma or serum. Previous methods utilizing
      gas-liquid chromatography (GLC) alone are time consuming and are hampered by
      interference from cholesterol derivatives. We describe here a GLC-mass
      spectrometry method for the simultaneous quantification of VLCFAs and phytanic
      acid. The method employs single ion monitoring with deuterated internal
      standards. We studied 38 normal controls and 12 patients with peroxisomal
      diseases and found complete discrimination between the two groups. Comparison
      with other methodology is discussed. We believe this to be a practical and
      accurate method for the quantification of both VLCFAs and phytanic acid in serum
      or plasma. It should be useful for laboratories involved in the diagnosis of
      biochemical disorders.

PMID- 7522997
TI  - Chemiluminescent enzyme immunoassay of prostate-specific antigen based on indoxyl
      phosphate substrate.

PMID- 7522998
TI  - Association of pancreatic adenocarcinoma, mild lung disease, and delta F508
      mutation in a cystic fibrosis patient.
AB  - A case of adenocarcinoma of the pancreas and mild lung disease in a 39-year-old
      man homozygous for the delta F508 cystic fibrosis mutation is presented. Cystic
      fibrosis is the most common lethal genetic disease in Caucasians, and is most
      commonly associated with severe obstructive lung disease. To our knowledge, this
      is only the fifth case of adenocarcinoma of the pancreas in a CF patient to be
      reported and the first case for which molecular data are available. The rare
      incidence of this type of malignancy in the general population suggests a
      possible association of CF with this malignant disease.

PMID- 7522999
TI  - 5 alpha-reductase inhibitors and prostatic disease.
AB  - 5 alpha-Reductase inhibitors are a new class of substances with very specific
      effects on type I and type II 5 alpha R which may be of use in the treatment of
      skin disease, such as male pattern baldness, male acne and hirsutism, as well as
      prostatic hyperplasia and prostate cancer. At least two types of 5 alpha R
      inhibitors with a different pH optimum have been described. cDNA encoding for
      both the type I and the type II enzyme has been cloned. Most of the orally
      effective 5 alpha R inhibitors belong to the class of 4-azasteroids. The radical
      substituted in the 17 position of the steroid ring seems to be related to species
      specific variations and to the types of 5 alpha R enzymes in different species
      and organ systems. 5 alpha R inhibitors lead to a decrease of plasma DHT by about
      65% while there is a slight rise in plasma testosterone. The decrease of tissue
      DHT in the ventral prostate of the intact rat, the dog and in humans is more
      pronounced and amounts to about 85%. There is a reciprocal rise of tissue T in
      these systems. The application of an inhibitor of 5 alpha R type II leads to a
      shrinkage of BPH in men by about 30%. In the rat a similar shrinkage accompanied
      by a significant decrease of total organ DNA occurs. This decrease, however, is
      not as pronounced as can be achieved with castration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7523001
TI  - Glycoprotein hormone alpha-subunit secretion in prolactinomas and in non
      functioning adenomas: relation with the tumour size.
AB  - OBJECTIVE: Free glycoprotein hormone alpha-subunit plasma levels have been
      reported to be increased in glycoprotein hormone-secreting adenomas and in
      acromegaly, but rarely in prolactinomas and in only two cases of Cushing's
      disease. The prevalence of elevated plasma alpha-subunit levels in patients with
      non-functioning adenomas is still unclear. In addition, no previous work has
      described plasma alpha-subunit levels in a comprehensive series of adenomas
      characterized by in-vivo secretion and/or immunocytochemistry. PATIENTS: Thirty
      seven patients with definite prolactinomas and 48 with non-functioning tumours
      characterized by immunocytochemistry were studied, from a series of 145
      consecutive patients including 33 acromegalics, 18 patients with glycoprotein
      hormone-secreting adenomas and 9 with Cushing's disease. MEASUREMENTS: Plasma
      free alpha-subunit was measured by radioimmunoassay in all patients and in a
      large sample of normal subjects to establish normal ranges according to sex, age
      and menstrual status. Tumour volume index was the product in cm3 of length, width
      and height of the adenoma as assessed by computerized tomography or magnetic
      resonance imaging. RESULTS: Twelve of the 37 (32%) patients with prolactinomas
      had increased plasma alpha-subunit levels; their tumours were significantly
      larger with significantly higher plasma PRL levels than those of patients without
      increased plasma alpha-subunit levels (P < 0.02). All prolactinomas above 50 cm3
      were associated with alpha-subunit secretion, whereas only 6 of 29 smaller
      tumours were similarly associated. Twelve of the 48 'non-functioning' adenomas
      actually secreted alpha-subunit in vivo: 8 gonadotrophin-secreting, 2 'pure'
      alpha-secreting, one with negative immunocytochemistry and one necrotic adenoma.
      Their volumes were significantly higher than those of adenomas without increased
      plasma alpha-subunit levels (P < 0.04). Plasma alpha-subunit levels were
      increased in the 6 patients with TSH-secreting adenomas, 8 of 12 with FSH
      secreting adenomas, 11 of 33 acromegalics and none of those with Cushing's
      disease. CONCLUSION: Plasma free alpha-subunit levels were increased in 49 of 145
      patients (34%). For prolactinomas and 'non-functioning' adenomas, alpha-subunit
      hypersecretion was seen more often with larger tumours. Half of the cases with
      increased free alpha-subunit in this series were patients harbouring an adenoma
      which did not stain for an intact glycoprotein hormone.

PMID- 7523000
TI  - Inhibin as a marker for hydatidiform mole: a comparative study with the
      determinations of intact human chorionic gonadotrophin and its free beta-subunit.
AB  - OBJECTIVE: The purpose of the study was to evaluate plasma inhibin as a marker of
      hydatidiform mole and to compare the results with intact human chorionic
      gonadotrophin (hCG) and its free beta-subunit. DESIGN: Serial determinations of
      the plasma concentrations of inhibin, intact human chorionic gonadotrophin and
      its free beta-subunit in cases of hydatidiform mole over an average period of 140
      days. PATIENTS: Five cases of hydatidiform mole, including patients with
      spontaneous remission after evacuation or persistent trophoblastic disease.
      MEASUREMENTS: Immunoreactive inhibin, hCG and free hCG beta-subunit were measured
      using standard enzyme immunoassays. RESULTS: Inhibin and free hCG beta-subunit
      levels were greater than in normal pregnant women at the same gestational age.
      Only intact hCG could detect the persistence of trophoblastic tissue.
      CONCLUSIONS: Our data suggest that inhibin, intact human chorionic gonadotrophin
      and free beta-subunit might be useful as diagnostic markers of molar pregnancies.
      However, the original method of intact hCG determination is still superior for
      follow-up.

PMID- 7523002
TI  - Insulin-like growth factor binding protein 1 response to acute insulin induced
      hypoglycaemia in type 1 diabetes.
AB  - OBJECTIVES: Insulin is believed to be the prime regulator of insulin-like growth
      factor binding protein 1 (IGFBP-1) secretion, and in normal subjects acute
      insulin induced hypoglycaemia exerts a rapid effect on concentrations of IGFBP-1,
      and may also influence insulin-like growth factor I (IGF-I) concentrations. The
      rise in IGFBP-1 concentrations in normal subjects following hypoglycaemia has
      been suggested to be due to suppression of endogenous insulin secretion. We have
      examined this further by studying diabetics with no endogenous insulin secretion.
      DESIGN: We have compared the IGFBP-1 response to acute insulin induced
      hypoglycaemia in normal subjects and patients with Type 1 (insulin dependent)
      diabetes mellitus. METHODS: Insulin tolerance tests were performed using a bolus
      of insulin (0.15 U/kg), in six control subjects and six patients with Type 1
      diabetes. MEASUREMENTS: Serum levels of IGFBP-1, insulin, glucose, and IGF-I were
      measured at regular intervals during the insulin tolerance test. RESULTS: Blood
      glucose fell to a nadir which coincided with the onset of the acute autonomic
      reaction 'R' in both groups. The basal concentration of IGF-I was significantly
      lower in the diabetic group at 0.4 +/- 0.1 kU/l, compared to 0.9 +/- 0.1 kU/l in
      the control group, but there was no significant change in IGF-I concentrations in
      response to hypoglycaemia in either group. Hypoglycaemia provoked a fall in IGFBP
      1 in patients with Type 1 diabetes, from 38 +/- 9 micrograms/l basally to 17 +/-
      3 micrograms/l at R + 120 minutes, with a return to basal values of 45 +/- 11
      micrograms/l at R + 180 minutes. In the control subjects there was no fall in
      IGFBP-1, but a significant increase to 71 +/- 14 micrograms/l at R + 180 minutes.
      CONCLUSION: This difference in the IGFBP-1 response in the presence of a similar
      glucose response suggests that in Type 1 diabetes there may be different
      sensitivities to the actions of exogenous insulin on IGFBP-1 regulation.

PMID- 7523003
TI  - Congenital cutis laxa with ligamentous laxity and delayed development, Dandy
      Walker malformation and minor heart and osseous defects.
AB  - We present a female infant exhibiting congenital cutis laxa with retardation of
      growth and motor development, ligamentous laxity and congenital dislocation of
      the hips. This connective tissue disorder was associated with Dandy-Walker
      malformation, atrial and ventricular defect and minor bone abnormalities
      including multiple wormian bones, abnormal tubulation of long bones and absent
      twelfth pair of ribs. This association is believed to be unique.

PMID- 7523004
TI  - Central nervous system abnormalities in chromosome deletion at 11q23.
AB  - Two Japanese pediatric patients with terminal deletion of the long arm of
      chromosome 11 are described. Both had the morphological abnormalities of the 11q
      deletion syndrome, such as prominent epicanthal folds, broad flat nasal bridge
      with short, upturned nose, short philtrum with carp-shaped mouth, cardiac
      anomalies and nonprogressive moderate psychomotor developmental delay. Patient 1
      is the first case to be reported with 11q deletion with serial magnetic resonance
      (MR) examinations of cerebral white matter. The initial MR imaging studies
      demonstrated multiple areas of T1 and T2 prolongation in the cerebral white
      matter in both patients at the ages of 2 5/12 and 2 1/12 years, respectively. A
      second MR imaging, performed 1 year after the first in Patient 1, demonstrated
      slight improvement of the lesions. Neither patient showed clinical deterioration.
      These results suggest that the lesions were caused by delayed myelination, rather
      than by demyelination. It is suggested that an unknown factor which is important
      for myelination is located on the long arm of chromosome 11: perhaps the neural
      cell adhesion molecule (NCAM).

PMID- 7523006
TI  - Endothelial cell activation by tumour necrosis factor-alpha (TNF-alpha) and the
      development of pre-eclampsia.
AB  - Pre-eclampsia may develop as a result of an endothelial activation. Tumour
      necrosis factor-alpha (TNF-alpha) activates endothelial cells which release
      soluble E-selectin, a putative circulating marker specific for endothelial
      damage. A retrospective longitudinal study of maternal blood samples, collected
      at different gestational ages in pregnancy, was undertaken to determine whether
      the development of pre-eclampsia is associated with TNF-alpha-mediated
      endothelial activation. This study included 19 women who developed pre-eclampsia
      and 22 women whose pregnancy outcome was normal. Ten women had blood samples
      taken before pre-eclampsia was clinically detected and, in all these, TNF-alpha
      was below the immunoassay limit of detection (< 80 pg/ml). Five had further
      samples taken after pre-eclampsia was clinically diagnosed and, initially, TNF
      alpha was still below the lower limit of detection in all five pregnancies, but
      rose later in three (80, 156 and 250 pg/ml). In nine other patients with
      diagnosed pre-eclampsia, TNF-alpha was detected in only two (80 and 650 pg/ml).
      TNF-alpha was identified in only one of the 22 normal pregnancies (80 pg/ml),
      this being at term. There was no statistical difference in soluble E-selectin
      levels between normal and pre-eclamptic pregnancies, neither before nor after pre
      eclampsia was diagnosed. Hence, blood TNF-alpha levels measured by immunoassay
      can be elevated in approximately 36% of cases of established pre-eclampsia, but
      this rise occurs only after the syndrome is detected clinically. Blood
      concentrations of TNF-alpha and soluble E-selectin are not related to severity of
      the disorder. These findings suggest that circulating TNF-alpha does not
      contribute to the initiation of endothelial cell activation that may be
      associated with the development of pre-eclampsia, but may rise as a consequence
      of the pathological processes of this disorder.

PMID- 7523007
TI  - Progressive increase of CD7- T cells in human blood lymphocytes with ageing.
AB  - CD7 is one of the major surface antigens expressed very early during T cell
      ontogeny. Lack of CD7 expression on mature T cells is regarded as a classical
      feature of malignant T cells in certain forms of cutaneous T cell lymphoma.
      Previously, we identified a CD7- subset of peripheral blood T lymphocytes in
      normal human individuals. In this study we determined the portion of CD7- T cells
      in the peripheral blood of healthy volunteers ranging in age from 8 months to 90
      years (n = 85) and in cord blood of full-term infants (n = 14). Furthermore, this
      CD7- subset was characterized in detail by the use of MoAbs and three-colour flow
      cytometry. In cord blood no CD7- T cells could be detected. After birth,
      percentage and absolute number of CD7- T cells increased with age. Independently
      of age, most CD7-CD3+ cells belonged to the CD4+ subpopulation. Focusing on the
      latter we could demonstrate the predominance of the CD45RO+CD45RA- phenotype in
      the CD7- subset. Furthermore, CD7- T cells contained a higher number of cells
      expressing activation markers and the CD57 antigen, but a reduced number of
      CD62L+ cells in comparison with CD7+ T cells.

PMID- 7523008
TI  - Autoreactive IgG elicited in mice by the non-dominant but pathogenic
      thyroglobulin peptide (2495-2511): implications for thyroid autoimmunity.
AB  - We have previously shown that mice challenged with the rat thyroglobulin (Tg)
      peptide TgP1 (corresponding to aa 2495-2511 of human Tg) develop experimental
      autoimmune thyroiditis (EAT) and produce IgG antibodies that cross-react with Tg
      from various species. It was not clear, however, whether such antibodies were
      TgP1-specific or were induced secondarily--i.e. by autologous Tg released from
      the destroyed gland--and therefore directed to determinants other than TgP1. In
      this study we describe that, 5 weeks after priming with TgP1, the binding of
      serum IgG on native Tg is completely inhibited by free peptide, suggesting lack
      of recognition of other determinants on mouse Tg (mTg). In addition, TgP1-induced
      but not mTg-induced IgG bound better to heat-denatured than intact mTg, a result
      compatible with the recognition of a linear epitope by the peptide-induced
      antibodies. Comparison of the IgG subclass distribution among mTg-induced versus
      TgP1-induced IgG did not reveal qualitative differences, since all subclasses
      were represented in the order IgG1 > IgG2b > IgG2a > IgG3. Finally, TgP1-specific
      IgG reacted strongly with the follicular colloid in sections of normal thyroids,
      indicating the potential to bind to native Tg in vivo. These data: (i) highlight
      TgP1 as the only, so far, Tg sequence known to generate both EAT and Tg-reactive
      IgG in mice; and (ii) do not provide evidence for an amplification of the Tg
      specific IgG response through the involvement of endogenous autoantigen in EAT.

PMID- 7523005
TI  - Mapping of B cell epitopes on steroid 17 alpha-hydroxylase, an autoantigen in
      autoimmune polyglandular syndrome type I.
AB  - Earlier studies have shown that 17 alpha-hydroxylase (P450c17), steroid 21
      hydroxylase (P450c21) and side-chain cleavage enzyme (P450scc) are the main
      autoantigens recognized by sera from patients with Addison's disease associated
      with autoimmune polyglandular syndrome type I (APS I). In this study we tried to
      identify the autoantigenic epitopes on P450c17 and compared the identified
      sequences with corresponding regions in two other adrenal autoantigens, P450scc
      and P450c21. A series of P450c17 cDNA fragments was expressed in Escherichia coli
      and the recognition of the corresponding protein fragments by patient sera was
      tested by immunoblotting. Four distinct epitope regions (ER) were found: ER1
      (amino acids 122-148), ER2 (280-304), ER3 (396-432) and ER4 (466-508). B cell
      epitope prediction analysis showed that the four identified ERs were all located
      in regions of high predicted antigenicity. Homology search revealed that ER3 and
      ER4 but not ER1 and ER2 were related to similar sequences on P450c21. No
      significant homologies with P450scc in these regions were found. Although all
      three P450 cytochromes are genuine autoantigens this finding suggests that the
      autoantibody reaction against P450c17 and P450c21 can partly be a result of
      immunological cross-reactivity.

PMID- 7523010
TI  - Inhibition by ethacrynic acid of NO-mediated relaxations of the rat anococcygeus
      muscle.
AB  - 1. The effects of ethacrynic acid were studied on relaxations elicited by nitric
      oxide (NO), the NO-donors sodium nitroprusside (SNP) and glyceryl trinitrate
      (GTN), nitrergic nerve stimulation and the NO-independent agent papaverine in
      isolated preparations of rat anococcygeus muscles. 2. Ethacrynic acid (100
      mumol/L) produced complete relaxation of partially contracted anococcygeus
      muscles, but the tone recovered after the ethacrynic acid was washed out.
      Following exposure to ethacrynic acid, the relaxant responses to NO, SNP, GTN and
      nitrergic nerve stimulation were abolished or markedly reduced; however, the
      response to papaverine was only slightly reduced. 3. The presence of 3 mmol/L L
      cysteine during the period of exposure to ethacrynic acid prevented the
      inhibition of the relaxing effects of SNP, GTN and nitrergic nerve stimulation
      almost completely, but did not affect the slight reduction in responses to
      papaverine. 4. The addition of L-cysteine (3 mmol/L) after incubation with
      ethacrynic acid did not significantly affect the inhibited responses to SNP and
      GTN; however, the inhibited responses to nitrergic nerve stimulation were
      slightly but significantly increased. 5. The results suggest that endogenous
      sulphydryl groups are required for the actions of NO, NO-donating drugs and the
      nitrergic transmitter in the rat anococcygeus muscle and possibly for the
      synthesis or release of the nitrergic transmitter.

PMID- 7523009
TI  - Analysis of idiotope structure of ovarian cancer antibodies: recognition of the
      same epitope by two monoclonal antibodies differing mainly in their heavy chain
      variable sequences.
AB  - Two MoAbs, independently raised against ovarian carcinoma cells and referred to
      as OV-TL3 and OV-TL16, display an identical reaction pattern with a membrane
      associated protein in both normal and malignant ovarian cells. Also, a similar
      binding affinity constant and a similar number of binding sites per cell indicate
      that both MoAbs bind to the same antigen. Competition assays reveal that OV-TL16
      is able to compete with OV-TL3 for binding to OVCAR-3 cells. Epitope mapping
      using a filamentous phage hexapeptide epitope library showed that both MoAbs are
      able to select identical phages, suggesting that their epitopes are identical or
      at least overlapping. However, purified polyclonal and monoclonal anti-idiotypic
      antibodies directed against OV-TL3 failed to recognize the OV-TL16 idiotype,
      indicating that the structure of the antigen-binding regions of both antibodies
      is distinct. This was corroborated by molecular cloning and sequencing of the
      variable heavy (VH) and light (VL) chain immunoglobulin regions of both MoAbs.
      The VH regions of both antibodies were found to be distinct, whereas the VL
      regions are almost identical. Computer modelling of the idiotypes suggests that
      the complementarity determining regions (CDR), with the exception of VHCDR3, have
      (almost) identical spatial configurations. Our data indicate that, although
      structurally different in their VH regions, OV-TL3 and OV-TL16 are able to bind
      to identical epitopic regions on the antigen, because differences in primary
      structure do not exclude the formation of sufficient and similar spatial
      structures for the interaction with an epitope.

PMID- 7523011
TI  - Expression and function of Fas antigen and bcl-2 in human systemic lupus
      erythematosus lymphocytes.
AB  - Studies indicate that autoimmune phenomena might be caused by a failure to
      eliminate autoreactive lymphocytes. Therefore, we examined Fas antigen and bcl-2
      expression and function in lymphocytes from human systemic lupus erythematosus
      (SLE) patients. Freshly isolated lymphocytes from patients with active SLE
      expressed more Fas antigen than did lymphocytes from patients with inactive SLE
      or from normal controls. They also showed characteristic DNA fragmentation after
      treatment with anti-Fas antibody. Expression of bcl-2 in T cells from active SLE
      patients was significantly higher than that in cells from inactive SLE patients
      and from normals. These data suggest that lymphocytes in patients with active SLE
      maintain an activated state in vivo. However, the role of Fas and bcl-2
      expression in the regulation of lymphocyte survival in SLE is still unclear and
      further investigations concerning the role of these molecules in autoimmune
      phenomenon in SLE are needed.

PMID- 7523012
TI  - A case of germinal center formation by CD45RO T and CD20 B lymphocytes in
      rheumatoid arthritic subchondral bone: proposal for a two-compartment model of
      immune-mediated disease with implications for immunotherapeutic strategies.
AB  - In rheumatoid arthritis (RA) disease activity occurring as joint destruction of
      cartilage and bone is thought to be driven by inflammatory reactions which are
      initiated by exogenous microbial mechanisms and perpetuated by endogenous
      autoimmune mechanisms. According to the synovial model of RA, these reactions
      originate in the adjacent synovial tissues. The following set of observations is
      presented herein to suggest an alternate model involving subchondral bone.
      Lymphocytic infiltrates accompanied by immunoglobulin deposits were identified in
      rheumatoid subchondral bone near areas of cartilage undergoing destruction by
      local subchondral inflammation. CD45RO T lymphocytes also were identified with
      these infiltrates as well as with CD20 B lymphocytes in an area of subchondral
      bone containing a well-organized germinal center. Analysis of extracts of
      rheumatoid subchondral bone revealed a high incidence of autoantibodies directed
      against type II collagen, the major protein constituent of cartilaginous tissue.
      Analysis of IgG subclass and cyanogen bromide peptide specificity revealed a
      pathogenic subset of these autoantibodies. A passive transfer study utilizing
      similar antibodies from collagen arthritic animals confirmed that such
      autoantibodies would have the potential of contributing directly to disease
      activity observed in rheumatoid subchondral bone. These studies suggest that (i)
      subchondral bone may be playing an active role in RA as a local site of immune
      mediated disease activity and (ii) basic and therapeutic studies aimed at
      understanding and eventually controlling RA should be diversified to include the
      study of not only synovial tissue, but also subchondral bone as a local source of
      the antigenic, cellular, and humoral immune components of joint destruction.

PMID- 7523013
TI  - Suppression of cytokine-dependent human T-cell proliferation by intravenous
      immunoglobulin.
AB  - Human intravenous immunoglobulin (hIVIG) modifies the course of numerous immune
      mediated diseases, but its specific mode of action remains unknown. In order to
      delineate possible immunoregulatory mechanisms, we studied the effects of hIVIG
      on the in vitro proliferation of human T cells. Cells from normal donors were
      stimulated with anti-CD3 antibody, tetanus toxoid antigen or the combination of a
      phorbol ester/ionomycin (P/I) and incubated with increasing concentrations of
      hIVIG (1 mg/ml to 10 mg/ml) for three to seven days. Addition of hIVIG inhibited
      anti-CD3 and tetanus but not P/I-induced proliferation in a dose-dependent
      manner. Addition of exogenous IL-2 to the cultures overcame the inhibitory effect
      of hIVIG; addition of IL-4 was ineffective. To further define the effect of hIVIG
      on specific cell populations, competent, purified T cells were stimulated with
      anti-CD3 or phorbol ester for three days in the presence of hIVIG. Addition of
      hIVIG blocked anti-CD3 and phorbol ester-induced stimulation of competent T
      cells. In cultures of competent T cells, either IL-2 or IL-4 was successful in
      reversing the hIVIG-induced inhibition. In these cultures, hIVIG also
      significantly prevented the synthesis/secretion of both IL-2 and IL-4 in PDB
      stimulated competent T cells. Taken together, these data suggest that one
      mechanism of action of hIVIG may be through its interference with cytokine
      dependent T-cell proliferation.

PMID- 7523014
TI  - HIV-1 gp160 as a modifier of Th1 and Th2 cytokine response: gp160 suppresses
      interferon-gamma and interleukin-2 production concomitantly with enhanced
      interleukin-4 production in vitro.
AB  - Disease progression in HIV-1 infection is reported to be associated with a
      gradual shift in CD4+ T cell function from a Th type 1 to a Th type 2 of
      response, but the underlying mechanism remains unclear. In this study, the effect
      of HIV-1 envelope glycoprotein gp160 on secretion of cytokines IFN-gamma/IL-2
      (Th1 type) and IL-4 (Th2 type) was analyzed using freshly isolated unfractioned
      peripheral blood mononuclear cells (PBMC), CD4+ T cell lines, and PBMC depleted
      of CD8+ cells (CD8- PBMC) as target cells. Pretreatment of these cells with HIV
      gp160 significantly reduced PHA-induced secretion of IFN-gamma and IL-2 but
      augmented IL-4 production. This effect of gp160 was not observed when the target
      cells consisted of PBMC depleted of either CD4+ cells (CD4- PBMC) or of CD2+
      cells (CD2- PBMC). Pretreatment of gp160 with soluble CD4-immunoglobulin chimeric
      molecules abrogated the observed effects of gp160, suggesting that CD4-gp120
      interaction is required for modification of the cytokine secretion profile. Our
      results suggest that exposure of CD4+ T cells to HIV-1 envelope proteins may
      modify the responses evoked by additional stimuli in favor of a Th2-type dominant
      response.

PMID- 7523017
TI  - Quantitative light microscopy. A powerful tool to assess bone.
AB  - Quantitative light microscopy is an important tool for assessing objectively the
      status of histologic events. It is, therefore, extremely useful for studying the
      dynamics of bone. This article provides a brief description of three quantitative
      techniques that are applicable to histomorphometry.

PMID- 7523015
TI  - Upregulation of AP-2 in the skin of Xenopus laevis during thyroid hormone-induced
      metamorphosis.
AB  - During amphibian metamorphosis dramatic changes occur in the morphogenesis and
      differentiation of the epidermis. Concurrently with these changes, the 63 kDa
      keratin gene is upregulated from low basal levels to high levels. What makes
      these processes unique is that they are controlled by triiodothyronine (T3) and
      can be duplicated in cultures of purified epidermal cells. Since there is a 2 day
      lag period between the addition of T3 and the upregulation of keratin gene
      expression and terminal differentiation, recent studies have focused on
      identifying the genes activated during the lag period. We assume that the
      transcription factors required for upregulation of the keratin gene are induced
      by T3 during the lag period, and therefore we have cloned the keratin gene so
      that promoter analyses can be conducted. S1 mapping assays have shown that the
      same transcription start sites are used during premetamorphosis when the keratin
      gene is basally expressed, during metamorphosis when it is T3-upregulated, and in
      the adult epidermis where it is expressed independently of T3. During the early
      part of the lag period TR beta and AP-2 mRNA levels are upregulated in the
      epidermis by T3. The transcription factor AP-2 is expressed at high levels in the
      skin of premetamorphic larvae and induced about fivefold by T3 but is not induced
      in an epithelial cell line (XL-177). Since the keratin mRNA, AP-2 mRNA, and other
      genes induced during the lag period are expressed in premetamorphic larvae it
      appears that T3 functions by upregulating the expression of genes previously
      activated by a T3-independent process. This preprogramming may account for the
      tissue specificity of T3 action during metamorphosis.

PMID- 7523016
TI  - Development and significance of nucleoside drug resistance in infection caused by
      the human immunodeficiency virus type 1.
AB  - Nucleoside antagonists of human immunodeficiency virus (HIV) reverse
      transcriptase (RT) activity have been commonly used in the therapy of HIV
      associated disease. The prolonged use of such drugs has led to the development of
      HIV variants that display resistance against these compounds. HIV drug resistance
      has been documented clinically for each of the following nucleosides: 3'-azido-3'
      deoxythymidine (AZT; zidovudine, ZDV), 2',3'-dideoxyinosine (ddI; didanosine),
      and 2',3'-dideoxycytidine (ddC; zalcitabine). In addition, resistance has been
      demonstrated against a series of non-nucleoside inhibitors of the viral RT.
      Several groups have documented that a series of point mutations within the HIV
      pol gene, that encodes the RT enzyme, is responsible for HIV drug resistance.
      Diminished sensitivity to anti-viral drugs results from both the selective
      pressure exerted by these compounds in individuals receiving prolonged therapy
      and the error-prone nature of the viral RT itself, thus permitting the outgrowth
      of mutated forms. Patients suffering from both disease progression and/or low CD4
      counts are most likely to develop HIV drug resistance.

PMID- 7523019
TI  - Clinical application of reverse transcription-polymerase chain reaction for HIV
      infection.
AB  - This article describes the current knowledge of the various RT-PCR assays and
      their clinical application in HIV disease. The importance of assay precision and
      sample handling is emphasized. A review of quantification techniques is also
      presented. Finally, the relevant literature describing the application of RT-PCR
      for both virion RNA in plasma and cellular mRNA is reviewed.

PMID- 7523018
TI  - Cellular localization of inducible nitric oxide synthase in experimental
      endotoxic shock in the rat.
AB  - 1. Endotoxin induces a shock-like syndrome with increased nitric oxide synthesis.
      To clarify the cellular source of NO in endotoxic shock we used
      immunohistochemistry and in situ hybridization to localize inducible NO synthase
      in rats given lipopolysaccharide or Corynebacterium parvum and
      lipopolysaccharide. Immunohistochemistry was carried out with an antibody raised
      against a synthetic peptide of mouse macrophage NO synthase. In situ
      hybridization was performed with 35S-labelled oligonucleotide probes
      corresponding to cDNA sequences common to mouse macrophage inducible NO synthase
      and rat vascular smooth inducible NO synthase. Monocytes and macrophages were
      identified by immunohistochemistry with the mouse monoclonal antibody ED1. 2.
      After lipopolysaccharide alone, the major site of NO synthase induction was
      monocytes and macrophages in multiple organs, principally liver and spleen.
      Bronchial, bile duct, intestinal and bladder epithelium and some hepatocytes also
      expressed inducible NO synthase. Expression peaked at 5 h and had returned to
      normal by 12 h except in spleen. 3. After priming with C. parvum,
      lipopolysaccharide led to a similar distribution of inducible NO synthase as
      lipopolysaccharide alone, but in addition there was more prominent hepatocyte
      staining, staining in macrophage granulomas in the liver and inducible NO
      synthase was present in some endothelial cells in the aorta. 4. These findings
      provide a direct demonstration of the cellular localization of inducible NO
      synthase after lipopolysaccharide.

PMID- 7523020
TI  - Therapy other than reverse transcriptase inhibitors for HIV infection.
AB  - Antiretroviral drugs against HIV infection have been developed that inhibit
      various stages of the HIV replication cycle. Agents other than reverse
      transcriptase inhibitors are reviewed with particular attention to those under
      study in clinical trials, including inhibitors of the virus-encoded protease
      enzyme. In addition, innovative strategies using gene therapy are described. It
      is concluded that combinations of agents may be the best approach for minimizing
      toxicity and reducing or delaying the emergence of drug-resistant virus during
      therapy.

PMID- 7523021
TI  - HIV-1 drug resistance. Molecular pathogenesis and laboratory monitoring.
AB  - Molecular and clinical aspects of HIV-1 pathogenesis are described, including the
      turnover of the HIV-1 population in vivo, the clinical significance of resistance
      to HIV-1 reverse transcriptase (RT) inhibitors, and the inter-relationship
      between virus replication and RT inhibitor resistance. The molecular genetics of
      RT inhibitor resistance, including interactive effects of different RT mutations
      and the implications of those effects for combination chemotherapy, are
      summarized. Structural studies of RT and the biochemical bases of drug resistance
      are discussed.

PMID- 7523022
TI  - Protein contact dermatitis associated with food allergy to fish.

PMID- 7523023
TI  - Hospice: beyond boundaries.

PMID- 7523024
TI  - Cryopreservation of the common carotid artery of the rabbit.
AB  - We describe experiments on the cryopreservation of the rabbit common carotid
      artery aimed at improving upon previous results. We describe the design of a
      double clamp which holds the artery during transportation and storage, preventing
      twisting, shortening, and collapse of the vessel. The device allowed perfusion
      with solutions as desired and markedly reduced the extent of endothelial loss
      during procurement and processing. We also studied the effects of three vehicle
      solutions; a modified Hanks' solution, a solution originally developed for the
      cryopreservation of smooth muscle (K-Pipes), and a solution designed for corneal
      endothelium (CP-Tes). The criteria used to make the assessments were smooth
      muscle contractility and the structure and function of the vascular endothelium.
      A new staining method for vascular endothelium (combining propidium iodide with
      silver nitrate) is described. We found that there was significantly more
      endothelial cell damage in rabbit carotid arteries frozen in Hanks' solution than
      in the other solutions, and the recovery of smooth muscle contractility was
      lowest in the Hanks' group. Arteries cryopreserved using CP-Tes as the vehicle
      solution showed less endothelial cell damage than arteries preserved with either
      K-Pipes or Hanks' solution, and these arteries also exhibited the greatest
      relaxation response to acetylcholine. We conclude that careful handling of the
      vessels is important; of the solutions studied, CP-Tes is preferred for the
      cryopreservation of rabbit carotid artery with Me2SO.

PMID- 7523028
TI  - Effects of endothelin-1 on intraocular pressure and aqueous humor dynamics in the
      rabbit eye.
AB  - The effects of endothelin-1 (ET-1) on intraocular pressure (IOP) and aqueous
      humor dynamics were studied in the rabbit eye. The intravitreal injection of 10(
      5) M ET-1 (20 microliters) produced a biphasic IOP response consisting of an
      initial rise of 1 to 2 hours in duration, and a subsequent prolonged reduction
      lasting for more than 96 hours. Aqueous humor dynamics were determined 24 hours
      after the 10(-5) M ET-1 injection. Aqueous humor formation, measured
      fluorophotometrically, was decreased by 58%. Total outflow facility increased by
      94%, according to measurement by two-level constant pressure perfusion. The
      change of uveoscleral outflow determined by fluorescein-dextran perfusion was not
      significant. The decrease in aqueous flow and the increase in total facility
      accounted for most of the IOP reduction after the ET-1 injection. Endothelin,
      which is endogenously present in the eye, may play a role in the regulation of
      intraocular pressure.

PMID- 7523026
TI  - Is vitrification sufficient to preserve liposomes during freeze-drying?
AB  - It has been suggested that stabilization of liposomes and proteins during freeze
      drying requires only that they be maintained in a vitrified (glassy) state. In
      the present paper we show that vitrification is indeed necessary. However,
      dextran, which exists as a glass at a higher temperature than does trehalose and
      thus might be expected to stabilize liposomes more effectively, preserves DPPC
      liposomes only when extremely large quantities of the dextran are added. Dextran
      does not stabilize egg PC liposomes and, in fact, inhibits the stabilizing
      effects of trehalose. Dextran also does not depress Tm in the dry phospholipids
      and shows no interaction with the polar headgroup, as assessed by infrared
      spectroscopy. Trehalose, by contrast, depresses Tm in dry egg PC by about 60
      degrees C and depresses vibrational frequency of the phosphate in the polar
      headgroup to the frequency seen in the hydrated lipid, an effect we ascribe to
      hydrogen bonding between the sugar and the polar headgroup. We conclude that
      while vitrification may be required it is not in itself sufficient to preserve
      freeze-dried liposomes.

PMID- 7523025
TI  - Effect of dimethylsulfoxide and hydroxyethyl starch in the preservation of
      fractionated human marrow cells.
AB  - Fractionated human bone marrow cells, isolated by density centrifugation, could
      be well cryopreserved in both a DMSO/HES/albumin mixture and the conventional
      cryoprotectant (DMSO/serum) with either a programmed freezer or a -80 degrees C
      freezer. A lower initial temperature rise and a delayed plateau phase in the
      mixture in comparison with those in the DMSO/serum were observed using a
      programmed procedure without heat fusion compensation. Plateau phase in the
      mixture could also be shortened with increased liquid nitrogen to minimize the
      transition phase duration. However, the method of mononuclear cells immersed in a
      -80 degrees C freezer and stored in liquid nitrogen is simple and easily
      standardized. Additionally, widely used lactated Ringer's solution instead of
      Normosol-R can be employed to prepare the mixture for the preservation of
      fractionated cells.

PMID- 7523027
TI  - Effects of calcium channel blockers on rabbit corneal endothelial function.
AB  - The effects of calcium channel antagonists and agents that alter intracellular
      Ca2+ mobilization on corneal endothelial function have been examined. All
      experiments, except where specifically designated, were performed in the
      continuous presence of extracellular Ca2+. Verapamil (at 50 microM) increased the
      swelling rate of corneas bathed in normal Ringer solution whereas nifedipine and
      diltiazem (both up to 100 microM) were without effect. The nifedipine analog
      nisoldipine caused corneal swelling at 10 microM and 50 microM but nimodipine was
      without effect. When briefly exposed to a Ca(2+)-free solution corneal swelling
      was enhanced after subsequent exposure to 50 microM verapamil in normal Ringer
      but not after 50 microM diltiazem in normal Ringer, indicating that Ca2+ entry
      from the bathing solution into the cell was important and was apparently impeded
      by verapamil. Cadmium (0.6 and 1 mM) but not nickel (up to 250 microM) caused
      swelling of corneas bathed in normal Ringer. A Ca2+ channel agonist, BAY-K-8644,
      alone did not influence corneal thickness but when presented to the endothelium
      with 50 microM verapamil the swelling rate was much reduced compared to verapamil
      alone. The agonist, therefore, presumably maintained some Ca2+ channels open in
      face of the Ca2+ channel blocker. An agent that inhibited the release of
      intracellular Ca2+ stores (TMB-8) caused an initial corneal swelling over the
      first 1.5 hr of perfusion but thereafter had no effect on corneal thickness. In
      the presence of continued extracellular Ca2+ one explanation for the results is
      that modulation of intracellular Ca2+ by agents that alter plasma membrane
      transfer of Ca2+ influences apical junction permeability.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7523029
TI  - The photodynamic occlusion of choroidal vessels using benzoporphyrin derivative.
AB  - We used benzoporphyrin derivative-monoacid (BPD-MA), a new photosensitizing
      agent, in photodynamic therapy (PDT) to occlude choroidal vessels in the rabbit.
      Using BPD-MA, seven dutch-belted rabbit eyes were photodynamically treated to
      achieve acute choroidal vessel closure. Fundoscopy, fluorescein angiography (FA),
      and histology were performed 1 hour, 1 day, 3 days, 7 days, 14 days, 21 days, and
      28 days after PDT. On FA, PDT-treated spots remained nonperfused until day 3 when
      gradual reperfusion from the periphery began to appear. By day 28 the area of PDT
      appeared completely reperfused. Histology of lesions showed acute damage to
      choroidal vascular endothelial cells and retinal pigment epithelial (RPE) cells.
      Over subsequent days, recovery of RPE cells and regeneration of large choroidal
      vascular endothelial cells occurred. In addition, retinal degeneration occurred
      gradually over the 28 days of follow-up. Since current argon laser therapy of
      retinal neovascularization causes immediate retinal damage, the ability to
      occlude choroidal vessels without inducing acute thermal damage holds promise for
      treating clinical pathologic conditions that feature abnormal neovascularization,
      such as age-related macular degeneration and diabetic retinopathy.

PMID- 7523030
TI  - Vitreal insulin-like growth factor binding proteins (IGFBPs) are increased in
      human and animal diabetics.
AB  - Although patients with diabetic retinopathy have been reported to have elevated
      vitreal IGF-I levels, it is not known whether diabetes also affects the levels of
      vitreal IGF binding proteins (IGFBPs) which control IGF's bioavailability. To
      address this issue, vitreal IGFBP levels were assayed in human diabetics, rats
      with streptozotocin-induced diabetes and galactose-fed dogs with diabetic-like
      retinopathy. Using 125I-IGF-II ligand blots, it was found that human diabetics
      have a 4-fold increase in vitreal IGFBP levels. Also, western blots on human
      diabetic vitreous reveal increased levels of IGFBP-2 and proteolytic fragments of
      IGFBP-3. IGF binding assays on vitreous from streptozotocin-treated rats (three
      months in duration) also indicate a 5-fold increase in IGF binding activity. IGF
      ligand blots using vitreous from rats with a shorter duration of diabetes (one
      month) show a 63% increase in IGFBP binding and a marked decrease in serum IGFBP
      binding. IGF ligand blots and IGFBP-2 and -4 western blots using vitreous from
      galactose-fed dogs with diabetic-like retinopathy exhibit a 6-fold increase in
      vitreal IGFBPs. The observation that vitreal IGFBPs are elevated in diabetic
      humans and rats without overt retinopathy suggests that these increases are not
      the result of a preexisting end-stage retinopathy but rather are an early ocular
      event in the diabetic process. Increases in vitreal IGFBPs thus could participate
      in the proliferative aspects of diabetic retinopathy by virtue of their putative
      intrinsic bioactivity or their capacity to alter IGF bioavailability.

PMID- 7523031
TI  - Envelope sequence variation, neutralizing antibodies, and primate lentivirus
      persistence.
AB  - Studies in ungulate lentivirus systems clearly indicate that neutralization
      escape variants emerge over time in chronically infected animals. Studies in the
      EIAV system, in particular, have provided strong evidence that the humoral branch
      of the immune system is at least one selective force acting on an array of viral
      variants. In previous studies with the ungulate lentiviruses, molecularly cloned
      virus was never used, and plaque-purified virus was only sometimes used; the
      genetic determinants responsible for antigenic variation and immune selection
      were not determined. While molecular clones are available for HIV-1, immune
      selection studies have been hampered in this system by the fact that HIV-1 is
      infectious only for chimpanzees, which do not develop disease and are available
      in only limited numbers. Experiments on immune selection in humans are generally
      complicated by lack of knowledge on the time of infection and the genetic make-up
      of the infecting virus. Our studies on SIV immune selection summarized in this
      review provide definitive evidence that neutralization-resistant variants emerge
      in an individual during persistent infection by primate lentiviruses. By cloning
      viral envelope genes from rhesus monkeys over time and obtaining sequential serum
      samples from them, we have been able to study not only the evolution of envelope
      sequences but also the emergence of neutralization-resistant variants. Reciprocal
      neutralization studies were performed using parental and variant specific sera,
      and immune selection was demonstrated using molecularly cloned virus of defined
      sequence. During the course of persistent infection with SIV and HIV, there is
      clear selective pressure for change in discrete variable regions of envelope. The
      host neutralizing antibody response appears to be at least one of the selective
      forces driving sequence change in envelope since one result of the sequence
      variation is the emergence of neutralization escape mutants. This indicates that
      neutralizing antibodies do serve to limit HIV and SIV replication during the
      lengthy asymptomatic stage of infection. The coincidence of neutralization
      domains of HIV and/or SIV with variable regions V1, V2, V3, V4, V5, and V6
      suggests a direct relationship between neutralization domains and the emergence
      of sequence variants. However, different selective forces may be responsible all
      or in part for driving sequence changes in some variable domains (summarized in
      Table 2). For example, alterations in cell and/or tissue tropism may be
      responsible at least in part for driving change in V3 and the cytotoxic T
      lymphocyte response may be responsible for driving change in the signal peptide
      (V0; Henderson et al. 1992; Wei and Cresswell 1992).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7523035
TI  - Holter monitoring as a noninvasive indicator of cardiac involvement in
      sarcoidosis.
AB  - We investigated the usefulness of 24-h Holter monitoring for identification of
      myocardial involvement in 38 patients with sarcoidosis, including 12 patients
      with cardiac sarcoidosis, and 58 healthy controls. Ventricular ectopic beats
      (VEB) > or = 100 beats per day were detected in 8 (67 percent) of 12 patients
      with cardiac sarcoidosis, in 2 (8 percent) of 26 patients without cardiac
      sarcoidosis, and in 3 (5 percent) of 58 healthy controls. Holter monitoring was
      associated with a sensitivity of 67 percent and a specificity of 62 percent for
      cardiac sarcoidosis in the overall study population. In patients with
      sarcoidosis, specificity was 80 percent. Lown's grade 4 A and 4 B VEBs were
      detected in 8 (67 percent) of 12 patients with cardiac sarcoidosis, in 2 (8
      percent) of 26 patients with sarcoidosis without cardiac involvement, and in 2 (3
      percent) of 58 controls. Holter monitoring was associated with a sensitivity of
      67 percent and a specificity of 80 percent for identification of cardiac
      involvement in patients with systemic sarcoidosis. Our findings suggest that 24-h
      Holter monitoring provides a convenient and inexpensive means of noninvasive
      screening for cardiac involvement in generalized sarcoidosis, even in patients
      and outpatients who are without symptoms.

PMID- 7523033
TI  - Cytotoxic T lymphocytes in human immunodeficiency virus infection: responses to
      structural proteins.

PMID- 7523034
TI  - Pneumocystis carinii: antigenic, immunological, and molecular characterization.

PMID- 7523036
TI  - Chest radiography in patients with early stage prostatic carcinoma. Effect on
      treatment planning and cost analysis.
AB  - STUDY OBJECTIVE: An evaluation of the impact of routine preoperative chest
      radiographs was retrospectively undertaken in a pilot group of 292 patients with
      prostatic carcinoma who were part of a prospective study of prostate specific
      antigen screening for prostate carcinoma. DESIGN: Retrospective. SETTING:
      Hospital-based outpatients. PATIENTS AND PARTICIPANTS: A cost-effectiveness model
      was used to assess the value of routine chest radiography in this patient
      population. Chest radiography findings were categorized into four groups based on
      follow-up and impact. MEASUREMENTS AND RESULTS: Forty-three patients (15 percent)
      had a total of 45 positive findings on their chest radiographs. No patient had
      intrathoracic metastases from prostatic carcinoma. Only two patients (both with
      unsuspected second neoplasms) had findings that impacted on their treatment and
      one avoided retropubic radical prostatectomy. Total cost was $2,000 (based on
      Medicare reimbursement), or $14,000 (based on physician and hospital charges).
      CONCLUSION: Although benefit is small in terms of number of patients affected,
      clinical impact, in the two patients with significant findings, was great.
      Although cost-effectiveness cannot be confirmed on the basis of this series,
      further evaluation of its utility for this application should be undertaken.

PMID- 7523032
TI  - The class I-restricted cytotoxic T lymphocyte response to predetermined epitopes
      in the hepatitis B and C viruses.

PMID- 7523037
TI  - Urinary 5-HIAA unrelated to cystic fibrosis.

PMID- 7523038
TI  - Pleurodesis for spontaneous pneumothorax. Will the procedure of choice please
      stand up?

PMID- 7523039
TI  - Essential ingredients for an ideal education program for children with asthma and
      their families.

PMID- 7523040
TI  - [Molecular biology of pancreatic cancer: overexpression of fibroblast growth
      factors].
AB  - In the present study, the expression of a acidic fibroblast growth factor (aFGF),
      basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1
      were analyzed in 60 pancreatic cancer samples using Northern blot analysis,
      immunoblotting, in situ hybridization and immunohistochemical techniques. aFGF,
      bFGF and FGFR-1 were present in 63%, 55% and 52% of the tumor samples,
      respectively. Twenty-seven of the 60 pancreatic cancer tissue samples exhibited
      coexpression of aFGF and bFGF. In contrast, 14 of the tumor samples did not show
      immunoreactivity for aFGF or bFGF in the tumor cells. The expression of aFGF in
      the tumor cells had no influence on the postoperative survival period, whereas
      patients whose tumors were positive for bFGF and/or FGF-receptor-1 had
      significantly shorter postoperative survival periods. Our results suggest that
      bFGF and FGFR-1 may play a role in the growth behavior of pancreatic cancer and
      may contribute to tumor aggressiveness.

PMID- 7523041
TI  - [Tumoral vascular density in breast tumors and their effect on recurrence-free
      survival].
AB  - Angiogenesis quantitation of 106 patients with primary breast cancer and 35
      patients with adenofibroma of the breast was compared and examined to its
      prognostic relevance for five-years disease-free survival in breast cancer
      patients. Immunocytochemical staining for Factor VIII-related antigen was
      performed to outline vascular endothelium. We found a significant higher vessel
      density in breast cancer patients who experienced recurrence (17.4) than in those
      with no recurrence (9.4) or with adenofibroma (8.7) [p < 0.0001]. The probability
      of five-years recurrence-free survival for patients with a primary tumor of high
      vessel density was at 52.3% and 86.4% for tumors of low microvessel density (p <
      0.0011). Microvessel density proved to be an independent prognostic factor for
      breast cancer recurrence in the Cox-Model (relative risk 2.047, p = 0.0002).

PMID- 7523042
TI  - [Simplified combination bypass or biliodigestive anastomosis alone in
      nonresectable carcinoma of the head of the pancreas?].
AB  - Between January 1, 1986 and December 31, 1992 93 patients with irresectable
      carcinoma of the pancreatic head underwent surgical palliation: In group I (n =
      51) a single loop biliary (BB)- and gastric bypass (GB) was performed. 34 times
      the gastrojejunostomy was performed prophylactically. In group II (n = 42)
      surgical palliation was carried out only by biliary decompression in Roux-Y
      technique. In 30.9% gastric outlet obstruction (GOO) developed during follow-up.
      Both groups were comparable according to effectiveness of biliary drainage (93%
      (n = 42) (I); 97% (n = 38) (II)) with median post-operative bilirubin levels of
      3.21 mg/dl (I) and 4.1 mg/dl (II). Cholecysto-choledocho- and hepaticojejunostomy
      were equally effective. Median operative time, morbidity (19.6 (I) vs. 26.2 (II))
      and postoperative hospitalization were similar. Since there is a high frequency
      of secondary GOO after single BB we think that GB should be performed in all
      patients that undergo BB because secondary gastrojejunostomy at a later stage
      significantly increases morbidity and mortality.

PMID- 7523043
TI  - Bivariate flow karyotyping with air-cooled lasers.
AB  - An experimental flow cytometer was constructed using a quartz flow cell optically
      coupled to a 1.22 NA lens. A pair of crossed cylindrical quartz lenses allowed
      multilaser excitation. Two helium-cadmium (HeCd) lasers, emitting 16 mW at 442 nm
      and 35 mW at 325 nm, were used to excite chromomycin A3 and Hoechst 33258
      fluorescence, respectively. Bivariate flow karyotypes from normal human male
      chromosomes and from the Daudi cell line were obtained and were compared to those
      from a standard instrument using dual water-cooled lasers. The new experimental
      instrument exhibited comparable resolution to that from the standard instrument.
      In further experiments with Daudi chromosomes, the 35 mW HeCd laser was replaced
      with a 10 mW HeCd laser, and the system still gave good, though slightly
      decreased, resolution.

PMID- 7523045
TI  - Low level CD20 expression on T cell malignancies.
AB  - Although initially thought to be a B lineage restricted antigen, low "density" or
      antibody binding capacity (ABC) CD20 has recently been detected on subset(s) of
      normal T lymphocytes (Hultin et al.: Cytometry 14:196-204, 1993). We report low
      ABC CD20 expression in three (two children, one adult) cases of T-acute
      lymphoblastic leukemia (T-ALL). CD20 and other pertinent antigens were detected
      using a direct dual color method with a Becton Dickinson FACScan flow cytometer
      and Simulset software. Only one cell population based on light scatter was noted
      in each case that immunophenotypically represented almost a pure population of
      malignant cells expressing T lymphocyte antigens (for example, CD7 98%, 92%, and
      100%, respectively). A total of 95%, 87%, and 79% of the cells from the three
      cases expressed CD20 with an unusual low ABC compared to the customary "bright"
      CD20 expression on normal B lymphocytes. Other B lymphocyte associated antigens,
      such as CD19, CD22, Dr, and immunoglobulin light chains, were negative. Eleven
      other T lymphocytic malignancies from 1991 to 1993 were CD20 negative, including
      three other case of T-ALL (one adult and two children). One unusual case of
      intestinal small lymphocytic non-Hodgkin's lymphoma with a natural killer/T
      lymphocytic immunophenotype not described in this report appeared to be
      CD20"dim"+. Low ABC CD20 expression by T lymphocytic malignancies may provide a
      more unique immunophenotypic "fingerprint" to help support the diagnosis of T
      cell neoplasia vs. normal/reactive T cells (for example, low ABC CD20 cells
      represent only 2.4 +/- 1.5% of normal peripheral blood lymphocytes). This
      characteristic might also facilitate monitoring patients for residual or
      recurrent disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523044
TI  - Enhanced assessment of DNA/proliferative index by depletion of tumor infiltrating
      leukocytes prior to monoclonal antibody gated analysis of tumor cell DNA.
AB  - Flow cytometry has become an important tool for the analysis of breast tumors,
      and assessment of S phase fraction and DNA ploidy are potential indicators of
      tumor aggression. Due to masking or dilution of infrequent tumor cell events, the
      presence of normal cell types, such as inflammatory cells and fibroblasts, can
      interfere with accurate DNA analysis of solid tumor samples. MDA-MB-175-VII human
      breast carcinoma cells, WI-38 human lung fibroblast cells, and peripheral blood
      leukocytes were mixed, in varying proportions, in order to represent human breast
      tumor samples. The cells were subsequently treated with CD45 conjugated magnetic
      microspheres to deplete tumor infiltrating leukocytes, thus enriching for tumor
      cells. The tumor cell mixtures were then stained with a pan-cytokeratin specific
      monoclonal antibody or with a monoclonal antibody that reacts with breast
      epithelial membrane antigen (EMA). When used in combination with monoclonal
      antibody gating, utilization of this bead-based technology resulted in enhanced
      precision of DNA analysis.

PMID- 7523046
TI  - OKT4 epitope correlates with renal allograft survival in African Americans.
AB  - Flow cytometry was used to type the distribution of OKT4 and OKT4A epitopes in a
      population of African American renal allograft recipients. The prevalence of the
      OKT4A epitope is more common than previously described and is associated with
      increased graft survival.

PMID- 7523047
TI  - Effect of calcium channel agonist (BAY K8644) on volatile anesthetic-mediated
      depression in neonatal rabbit papillary muscle.
AB  - Heart muscle is dependent on the entry of calcium from the extracellular fluid to
      support contraction, and neonatal hearts are particularly sensitive to reductions
      in transsarcolemmal entry of calcium. Accordingly, this study evaluated the
      ability of the calcium channel agonist BAY K8644 to prevent or reverse the
      myocardial depressant effects of halothane or isoflurane in right ventricular
      papillary muscles from neonatal rabbits. The ability of BAY K8644 to reverse
      reductions in force (F) and dF/dt (halothane and isoflurane) or prevent reduction
      (halothane) was studied. Halothane decreased F to 24 +/- 2% of baseline values (p
      = 0.001). The addition of BAY K8644 reversed F to only 54 +/- 3% of baseline (p =
      0.001 vs. baseline and p = 0.002 vs. halothane alone). Isoflurane decreased F to
      20 +/- 2% of baseline (p = 0.001) with a return to 45 +/- 4% of baseline with the
      addition of BAY K8644 (p = 0.0001 vs. baseline and p = 0.0025 vs. isoflurane
      alone). With BAY K8644 in the bath prior to the addition of halothane, halothane
      decreased F to 38 +/- 4% of baseline (p = 0.001). dF/dt mirrored changes in F in
      all studies. These data show that a calcium channel agonist is only partially
      effective in modulating volatile anesthetic-induced depression in neonatal rabbit
      ventricular papillary muscle.

PMID- 7523048
TI  - CD5+ B-cells at the onset of type I diabetes and in the prediabetic period.
AB  - OBJECTIVE: B-cells expressing CD5 are associated with the production of
      autoantibodies and are present at increased levels in several autoimmune
      diseases. The aim of this study was to investigate the relationship of these
      cells to the development of type I diabetes and the presence of organ and non
      organ-specific autoantibodies. RESEARCH DESIGN AND METHODS: We measured
      percentage levels of CD5+ B-cells in patients with recent-onset (n = 34) and long
      standing (n = 21) type I diabetes and in a cohort of 18 identical twins of
      patients with type I diabetes studied prospectively, 8 of whom became diabetic
      (prediabetic twins) during the study; the rest remained nondiabetic after at
      least 7 years and are now unlikely to develop the disease. Forty-seven healthy
      individuals were studied as control subjects. RESULTS: Percentage levels of total
      B-cells (CD20+) and the proportion expressing CD5 were increased in patients with
      recent-onset (P < 0.001 for both) but not long-standing type I diabetes compared
      with control subjects. Percentage levels of CD20+ B-cells were increased in
      prediabetic twins throughout the prediabetic period (P < 0.05), and there was an
      increased proportion of CD5-expressing B-cells that failed to reach statistical
      significance (P = 0.08). Percentage levels of CD20+ B-cells and the proportion
      expressing CD5 were normal throughout the study in twins remaining nondiabetic.
      No relationship between percentage levels of CD5+ B-cells and islet cell
      antibody, thyroid autoantibodies, or non-organ-specific autoantibodies was found.
      CONCLUSIONS: These results show an increase in B-cell percentage levels at the
      diagnosis of type I diabetes, which is because of an expansion of the CD5+
      subset. These changes are also evident in twins throughout the prediabetic
      period, which suggests that they are related to the processes that lead to
      diabetes.

PMID- 7523049
TI  - Exocrine insufficiency in transplanted pancreas imitating pancreatic rejection.

PMID- 7523050
TI  - Paranuclear blue inclusions: an aid in the cytopathologic diagnosis of primary
      and metastatic pulmonary small-cell carcinoma.
AB  - Accurate diagnosis of small-cell carcinoma of the lung (SCLC) is clinically
      important because of the therapeutic implications. SCLC must be distinguished
      from non-small-cell carcinoma (NSCLC) and lymphoma. Paranuclear blue inclusions
      (PBIs) were recently described as a feature of metastatic SCLC on air-dried
      Wright-stained bone marrow aspirate smears. To determine the utility of PBIs in
      distinguishing SCLC from NSCLC and lymphoma, we evaluated air-dried Diff-Quik
      stained smears from 103 fine-needle aspiration (FNA) specimens and 14 touch
      imprint specimens. PBIs were identified in 24 (89%) of 27 cases of SCLC, in 6
      (9%) of 64 non-small-cell carcinomas (P < 0.00001), and in two (8%) of the 26
      lymphoma cases (P < 0.00001). No PBIs were seen on any of the alcohol-fixed
      Papanicolaou or hematoxylin-eosin (H&E) stained smears examined. In conclusion,
      PBIs appear to be a feature of SCLC on air-dried cytologic material stained with
      Romanowsky type stains. In the presence of cytologic features of SCLC, the
      identification of PBIs provides a useful diagnostic feature for differentiating
      between SCLC and NSCLC carcinomas, and between SCLC and lymphomas in FNA
      specimens and touch imprints from surgical specimens.

PMID- 7523052
TI  - [The value of Sm-153-EDTMP for treatment of metastatic bone pain and improving
      quality of life].
AB  - Sm-153-EDTMP (ethylenediaminetetramethylene phosphonic acid), a beta-particle and
      gamma-emitting radionuclide, was used for pain control of bone metastasis. Fourty
      patients with bone metastasis were administrated a single intravenous injection
      of 29.6 MBq/kg (0.8mCi/kg), and 7 of them received more than one injection. No
      obvious side effect was observed. The skeletal images obtained with Sm-153-EDTMP
      were similar to that of Tc-99m-MDP SPECT images. Follow up study (at least 30
      days) revealed bone pain relief and improved quality of life in 82.5% of the
      treated patients.

PMID- 7523051
TI  - Pharmacokinetics of polyvalent proteinase inhibitor (aprotinin) in eye tissues.
AB  - Drugs having as their active substance aprotinin (trasylol, gordox, etc.) are
      widely indicated in the treatment of eye pathologies having as their basis an
      enhanced proteolytic enzyme activation. Our studies have exposed a decrease in
      proteolytic activity in both eye tissues and tear fluid in response to Gordox
      administration. Up to date there are no works concerning pharmacokinetics of
      aprotinin in the eye tissues. The aim of this work was to study the
      pharmacokinetics of 125I-aprotinin in rabbit eye tissues after instillation. A
      presence of the substance was registered in the cornea, aqueous humor, and
      ciliary body within a period of 10-90 minutes after administration, but not in
      other tissues. Calculation of the pharmacokinetic parameters of aprotinin
      penetration in the eye showed that its mean residence time in the cornea, aqueous
      humor and ciliary body was 50-60 min. The addition of polyvinyl alcohol to the
      instillation solution increased the level of the substance in the tissues, but
      did not change its mean residence time. The medicine should be instilled every 1
      1.5 hrs to support high and stable levels of aprotinin in the eye.

PMID- 7523053
TI  - [Effects of recombinant stem cell factor on the proliferation in vitro of LT12
      acute promyelocytic leukemic cell line].
AB  - Stem cell factor is a recently identified earliest-acting hematopoietic growth
      factor and a ligand for the c-kit proto-oncogen. Based on our recent observations
      that recombinant rat interleukin-3 (IL3), human interleukin-6 (IL6) and murine
      granulocyte-macrophage colony stimulating factor (GM-CSF) possessed different
      degrees of suppressive activities on the proliferation of LT 12 cell line derived
      from BNML rat leukemic model, SCF was evaluated alone and in combination with
      either IL3, IL6 or GM-CSF for effects on leukemopoiesis in vitro. The results
      indicated that SCF alone had suppressive effect on DNA synthesis and colony
      forming unit-leukemic blast (CFU-L) in LT12 cells. 100ng/ml of SCF caused
      substantial reduction in colony number and 3H-TdR uptake although this
      suppression was of lower magnitude than those induced by IL3, IL6 or GM-CSF.
      Enhanced suppression on the proliferation of LT12 cells was observed when SCF was
      used in combination with one of these three factors. Among these combinations,
      SCF+GM-CSF or SCF+IL6 resulted in more suppression on LT12 cells than SCF+IL3
      did. Combination of SCF with two or three factors produced even more suppression.
      No apparent effect on the size of leukemic colony was seen. Furthermore, in
      growth kinetics study of LT12 cells in the presence of SCF production of LT12
      cells declined. Thus, SCF appears to have divergent hematopoietic activities on
      BNML rat model: effective stimulation of granulopoiesis and weak suppression of
      leukemopoiesis.

PMID- 7523054
TI  - Developmental potential of trunk neural crest cells in the mouse.
AB  - The availability of naturally occurring and engineered mutations in mice which
      affect the neural crest makes the mouse embryo an important experimental system
      for studying neural crest cell differentiation. Here, we determine the normal
      developmental potential of neural crest cells by performing in situ cell lineage
      analysis in the mouse by microinjecting lysinated rhodamine dextran (LRD) into
      individual dorsal neural tube cells in the trunk. Labeled progeny derived from
      single cells were found in the neural tube, dorsal root ganglia, sympathoadrenal
      derivatives, presumptive Schwann cells and/or pigment cells. Most embryos
      contained labeled cells both in the neural tube and at least one neural crest
      derivative, and numerous clones contributed to multiple neural crest derivatives.
      The time of injection influenced the derivatives populated by the labeled cells.
      Injections at early stages of migration yielded labeled progeny in both dorsal
      and ventral neural crest derivatives, whereas those performed at later stages had
      labeled cells only in more dorsal neural crest derivatives, such as dorsal root
      ganglion and presumptive pigment cells. The results suggest that in the mouse
      embryo: (1) there is a common precursor for neural crest and neural tube cells;
      (2) some neural crest cells are multipotent; and (3) the timing of emigration
      influences the range of possible neural crest derivatives.

PMID- 7523056
TI  - TGF beta 1 inhibits branching morphogenesis and N-myc expression in lung bud
      organ cultures.
AB  - Lung buds isolated from 11.5 days post coitum mouse embryos survive and undergo
      branching morphogenesis in culture. This organ culture system was used to examine
      the role of TGF beta 1 and N-myc expression in lung branching morphogenesis. By
      24 hours, TGF beta 1 reversibly inhibited branching morphogenesis in a
      concentration-dependent manner. N-myc is known to be expressed during embryonic
      development in epithelial cells involved in branching morphogenesis and
      homozygous null N-myc mice have defects in lung development. In the present
      study, TGF beta 1 was shown to inhibit the steady-state level of N-myc RNA 3- to
      4-fold at 14 and 48 hours of treatment as measured by northern blot and RNase
      protection analysis. Suppression of N-myc expression in epithelium was confirmed
      by in situ hybridization. Since inhibition of N-myc occurred prior to the
      observed changes in morphology and previous genetic studies have demonstrated and
      important role for N-myc in lung development, a model is proposed in which TGF
      beta 1 inhibits tracheobronchial development by inhibiting expression of N-myc.

PMID- 7523055
TI  - Transitional cells in the regenerating pancreas.
AB  - We examined the spectrum of intermediate cell types in the regenerating pancreas
      as duct epithelial cells progressed through their differentiation pathway to
      become mature endocrine cells. The model used was transgenic mice in which the
      pancreatic islets continue to grow during adulthood, unlike normal mice whose
      islet cell formation ceases early in life. Because the intermediate cells
      migrated into islet-like clusters at specific locations, we propose a specific
      pathway for islet development. Endocrine cells are derived from duct cells co
      expressing a duct cell antigen, carbonic anhydrase II (CA II) and an exocrine
      enzyme, amylase. The CA II/amylase cells become amylase/endocrine intermediate
      cells as they exited from their lumenal location. The abluminal amylase/endocrine
      cells continue to differentiate to multihormone-bearing young endocrine cells,
      which migrated to form clusters with other differentiating endocrine cells.

PMID- 7523058
TI  - Exercise testing in heart failure. A critical review.
AB  - Exercise intolerance is one of the primary characteristics of chronic congestive
      heart failure (CHF). Therefore, exercise testing has been widely used in the
      assessment of CHF patients, both to define the severity of the disease and to
      assess the efficacy of pharmaceutical agents in clinical trials. A number of
      different exercise tests can be used, although maximal exercise testing is the
      most common. Maximal exercise capacity can be determined by measuring exercise
      duration during incremental exercise, or maximal oxygen (O2) consumption, or it
      can be estimated by anaerobic threshold. While baseline exercise testing in CHF
      patients accurately identifies and quantifies cardiac failure and determines
      prognosis, it is of limited value in assessing changes that occur as a result of
      drug therapy. A key drawback of exercise testing as a measurement of drug effect
      is the fact that exercise changes produced by drug intervention do not correlate
      well with changes in the mortality rate. Several examples of the lack of
      correlation between exercise testing and mortality rates have been observed in
      clinical trials with angiotensin converting enzyme (ACE) inhibitors and
      vasodilators. ACE inhibitors have a modest effect on maximal exercise capacity
      but they improve survival. It is thought that neuroendocrine activation more
      closely reflects mortality rates and also the changes in survival observed with
      pharmacological intervention compared with other modes of evaluation.

PMID- 7523059
TI  - Exercise testing as outcome in congestive heart failure trials. Design
      considerations when interpreting results.
AB  - In addition to standard features of clinical trial design such as randomisation
      and double-blinding, sensitivity to drug effects is an important consideration
      when conducting exercise capacity trials in patients with heart failure. Two
      issues need to be addressed in this context. Firstly, it is important to enrol
      patients who are potential responders. Patients who have, for their age and sex,
      normal exercise capacity are unlikely to improve, even when given a drug that has
      a positive effect on exercise capacity. In addition, those patients who remain
      clinically stable following withdrawal of their previous drug therapy are
      unlikely to respond subsequently to an experimental drug with a similar mechanism
      of action. Secondly, failure to complete scheduled exercise tests during follow
      up, prompting a 'per-protocol' analysis of results, may mask the drug's actual
      effect. To avoid this, an 'intention-to-treat' approach to data collection and
      analysis, with appropriate allowance made for missing test data, should be
      adopted.

PMID- 7523061
TI  - Vascular versus myocardial effects of calcium antagonists.
AB  - As vascular smooth muscle tone and myocardial contractility both depend on
      calcium entry, the calcium antagonists are not only potent arterial vasodilators,
      but may also have important negative inotropic effects. For example, verapamil is
      nearly equipotent in reducing vascular smooth muscle tone and myocardial
      contraction in isolated tissue preparations. In contrast, felodipine has high
      vascular selectivity in such preparations, and drug concentrations required to
      depress myocardial contraction are more than 100 times greater than those
      required to relax vascular smooth muscle. In the isolated, isovolumetrically
      contracting canine left ventricle, clinically relevant concentrations of
      felodipine (14 nmol/L) produce coronary vasodilation and a mild positive
      inotropic response. Using left ventricular (LV) pressure-volume analysis, we
      evaluated a similar dose of felodipine (plasma drug concentration 16 nmol/L) in
      conscious dogs. Felodipine produced a 25mm Hg fall in arterial pressure and a 10%
      reduction in peripheral vascular resistance. There was no negative inotropic
      effect. Instead, myocardial contractile performance was slightly but
      significantly enhanced. These results were not altered by adrenergic blockade.
      Further studies in our laboratory showed that doses of amlodipine and nifedipine
      producing arterial vasodilation of a magnitude similar to that produced by
      felodipine had negative inotropic effects in the conscious dog. Only felodipine
      enhanced the rate of LV relaxation and the rate of early diastolic filling. Thus,
      felodipine was significantly more vasoselective than amlodipine and nifedipine.
      The direct inotropic effects of calcium antagonists are difficult to evaluate in
      clinical studies because of the load-dependence of most conventional measures of
      LV performance. However, no negative inotropic effects are clinically relevant
      doses of felodipine have been identified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523062
TI  - Vasodilators in heart failure. Conclusions from V-HeFT II and rationale for V
      HeFT III.
AB  - The Veterans Affairs Vasodilator-Heart Failure Trials (V-HeFT I and II) provided
      information about heart failure treated with conventional therapy, and evaluated
      the long term efficacy of vasodilators. In V-HeFT I, the combination of
      hydralazine and isosorbide dinitrate provided a beneficial effect on prognosis in
      heart failure. V-HeFT II demonstrated that enalapril had a more favourable effect
      on 2-year survival than a combination of hydralazine plus isosorbide dinitrate.
      However, the hydralazine-isosorbide dinitrate combination exerted the most
      favourable short term impact on exercise performance and left ventricular
      ejection fraction. The V-HeFT studies showed that, although not all vasodilators
      are alike, their differing effects might be beneficial when used in combination.
      Determination of the potential additive effect of the calcium antagonist
      felodipine, a vasodilator, when used in combination with an ACE inhibitor, is the
      major goal of V-HeFT III.

PMID- 7523063
TI  - Toxic PCB congeners and organochlorine pesticides in Italian human milk.
AB  - Human milk from four major Italian cities was analyzed for individual congeners
      of polychlorinated biphenyls (PCB), DDT, DDE, hexachlorobenzene, and beta
      hexachlorocyclohexane. Minimum and maximum concentrations in milk from individual
      mothers for most compounds ranged between one order of magnitude below and above
      the mean value of all mothers. Good agreements were found between results from
      pooled samples and mean values of individual samples. No statistically
      significant difference between cities was found and the levels in milk from
      Italian mothers did not differ significantly from published levels from other
      parts of the world. Principal component analyses revealed that the PCB congener
      distribution pattern was very similar in all mothers, independent of location.
      Average concentrations in milk from the four cities were 19(+/- 5) micrograms
      liter-1 total PCB or 3.2(+/- 0.8) ng liter-1 toxicity equivalents according to
      the most conservative TCDD toxicity equivalent factors of PCBs proposed in the
      literature, 70(+/- 18) micrograms liter-1 DDE, 4.5(+/- 1.2) micrograms liter-1
      DDT, 5.6(+/- 1.9) micrograms liter-1 HCB, and 4.4(+/- 1.7) micrograms liter-1
      beta-hexachlorocyclohexane.

PMID- 7523064
TI  - Toxicity of a new molt-inducing insecticide (RH-5992) to aquatic
      macroinvertebrates.
AB  - The molt-inducing insecticide RH-5992, a potent ecdysone agonist, is being
      evaluated for potential use in forestry to control defoliating lepidopterans. The
      possible adverse effects of RH-5992 on nontarget aquatic organisms were studied
      in two test systems. Acute lethal effects were determined for one aquatic
      amphipod and 11 species of aquatic insects in laboratory flowthrough toxicity
      tests. Lethal and behavioral effects (drift response) on the amphipod and 8
      species of stream insects were also evaluated under natural environmental
      conditions and more realistic exposure regimens in outdoor stream channels. There
      were no significant effects on drift or survival of the test species exposed to
      RH-5992 at the maximum test concentration of 3.5 mg/liter (100x the worst-case
      expected environmental concentration) in laboratory toxicity tests and stream
      channel treatments. Mortality of the amphipod Gammarus sp. in one toxicity test
      was considered an artifact, because there was no significant mortality in
      subsequent tests at concentrations up to 7.0 mg/liter, or in stream channels
      treated at 3.5 mg/liter. Yellow birch leaves were sprayed with RH-5992 at a rate
      of 50 g/ha and tested for residual toxic effects on two species of shredding
      invertebrates in the outdoor stream channels. There was no feeding inhibition or
      lethal effect on either test species resulting from consumption of the
      contaminated foliage. The candidate insecticide RH-5992 does not appear to pose
      undue risk of direct adverse effects to aquatic macroinvertebrates, particularly
      in water bodies where residues are likely to be short lived following aerial
      applications (e.g., lotic systems).

PMID- 7523065
TI  - Occurrence of toxic metabolites from nonionic surfactants in the Krka River
      estuary.
AB  - The occurrence and behavior of nonylphenol (NP), nonylphenol monoethoxylate
      (NP1EO), and nonylphenol diethoxylate (NP2EO) were studied in the Krka River
      estuary. Quantitative determinations using normal-phase high-performance liquid
      chromatography with spectrofluorimetric detection were performed in both
      municipal wastewaters and receiving estuarine waters. The concentrations of NP,
      NP1EO, and NP2EO in municipal wastewaters varied within the ranges of < 0.5-419,
      < 0.5-35, and < 0.5-54 micrograms/liter, respectively; thus, in general
      representing only a minor fraction of the total surfactant-derived nonylphenolic
      compounds. The concentration decrease after the wastewater discharge into the
      estuary was very sharp, which was assigned primarily to an efficient dilution of
      the wastewater plume. Consequently, the concentrations of NP, NP1EO, and NP2EO in
      the estuary were fairly low, the respective concentration ranges being < 20-1200,
      < 20-440, and < 20-1300 ng/liter. Rather complicated distribution patterns of NP,
      NP1EO, and NP2EO were obtained on the vertical profile of the estuarine water
      column with the concentration maxima at the estuarine phase boundaries, i.e., air
      freshwater and freshwater-seawater. Moreover, the ratio between individual
      nonylphenolic compounds varied significantly, indicating that transformation
      reactions played a significant role in their distribution and fate in the
      estuary.

PMID- 7523067
TI  - In vitro dose-response study of the effect of cadmium on eel (Anguilla anguilla)
      gill Na+/K(+)-ATPase activities.
AB  - The effect of cadmium exposure was studied in vitro on the ATPase activities of
      gill membrane microsomes from seawater- and freshwater-adapted eel (Anguilla
      anguilla) using a microassay technique. The basal activity (Mg(2+)-ATPase) was
      decreased by 40 and 25%, respectively, in seawater and freshwater preparations
      for the highest concentrations tested (respectively, 4 and 2 microM). The
      Na+/K(+)-ATPase activity was estimated either by potassium stimulation or by
      ouabain inhibition. This enzyme activity was inhibited by cadmium in a dose
      dependent manner with a I50 of 146 +/- 9.3 nM. Neither the technique used to
      measure the enzyme nor the adaptative environment significantly changed the I50.
      The results are compared to results obtained in other groups and to the effects
      of cadmium on metal ion exchanges in fish.

PMID- 7523057
TI  - Angiotensin as local modulating factor in ventricular dysfunction and failure due
      to coronary artery disease.
AB  - Congestive heart failure is the end product of a progressive series of events
      resulting from acute myocardial damage. Circulatory neurohormonal systems are
      activated during the acute phase of left ventricular dysfunction resulting from
      initial myocardial damage and again in the latter phase of decompensated heart
      failure. However, these neurohormonal mechanisms return to normal during the
      compensated stage of heart failure. Recent studies have suggested that
      autocrine/paracrine modulators of cardiovascular function are activated in the
      preclinical phase preceding the development of overt heart failure. The renin
      angiotensin system in particular has been shown to modulate many of the chronic
      processes involved in the pathophysiology of cardiovascular disorders. Recent
      studies suggest that locally generated angiotensin II may contribute to the
      secondary structural changes seen in cardiovascular disorders, such as cardiac
      hypertrophy and remodelling, coronary artery disease, and atherosclerosis. Thus,
      inhibition of angiotensin formation with angiotensin converting enzyme (ACE)
      inhibitors, particularly at the tissue level, may provide valuable
      cardioprotective effects. Additional evidence points to the efficacy of ACE
      inhibitors in preventing the progression of asymptomatic left ventricular
      dysfunction to overt heart failure.

PMID- 7523068
TI  - The relevance of aquatic organisms' lipid content to the toxicity of lipophilic
      chemicals: toxicity of lindane to different fish species.
AB  - The acute toxicity (48-hr LC50) of lindane (gamma-HCH) to 16 fish species,
      belonging to eight families, ranges from 22 to 900 micrograms/liter (mean: 150
      micrograms/liter). A significant positive linear relationship between the lipid
      content (% on a wet weight basis) of the fishes and their toxicity to gamma-HCH
      was found. If the toxicity is referred to 1% lipid, 48-hr LC50 values range
      between 13.2 and 32 micrograms/liter, and thus the coefficient of variation of
      the mean is reduced from 139 to 22%. It is concluded that the lipids of aquatic
      organisms serve as a protective reservoir against the toxic effects of lindane
      and other lipophilic, relatively persistent organic chemicals, because they are
      bioconcentrated mainly in the body lipids. Therefore, in organisms with high
      lipid content, only a relatively small fraction of the hydrophobic chemical can
      reach target organs (nerves, liver, etc.) and/or receptors. For comparing
      toxicity data of organic chemicals to aquatic organisms, the total lipid content
      of the organisms must be considered. The results of this investigation are
      important in comparative environmental toxicology for risk assessment of
      freshwater and marine organisms.

PMID- 7523060
TI  - The role of beta-blockers in the treatment of cardiomyopathy and ischaemic heart
      failure.
AB  - As first reported by our group in 1975, severe heart failure due to idiopathic
      dilated cardiomyopathy could be improved in patients receiving beta-blocker
      therapy starting at a very low dose and followed by a stepwise increase. Since
      then, these results have been confirmed by our own group and by others, and
      similar results were also obtained in patients with other forms of
      cardiomyopathy, including ischaemic cardiomyopathy. In 13 separate studies
      involving a total of 651 patients with idiopathic dilated cardiomyopathy, beta
      blockade for 2 to 19 months (in addition to conventional treatment of heart
      failure, including angiotensin converting enzyme inhibitor therapy),
      significantly improved cardiac function. These studies were performed using
      metoprolol, bucindolol, labetalol and practolol. Eight studies investigated the
      effects of long term beta-blocker treatment in patients with heart failure and
      cardiomyopathy due to coronary artery disease, valvular heart disease, diabetes
      and doxorubicin therapy. A total of 128 patients were treated with metoprolol,
      carvedilol or bucindolol for periods of 2 to 12 months. All studies reported a
      significant improvement in cardiac function. Three studies reported results on
      survival and the need for cardiac transplantation. The first study published by
      our group reported improved survival in patients with idiopathic dilated
      cardiomyopathy treated with metoprolol plus digitalis and diuretics compared with
      a matched control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523066
TI  - Induction of the hepatic biotransformation system of golden ide [Leuciscus idus
      (L.)] after exposure in the River Elbe.
AB  - The xenobiotic-metabolizing enzyme system of hatchery golden ide [Leuciscus idus
      (L.)] were tested for applicability in biological monitoring in rivers. The
      golden ide, cyprinid fish used for toxicity testing, were caged for 1 to 3 weeks
      in flowthrough systems at various locations of the river Elbe. The activities of
      7-ethoxycoumarin-O-deethylase (ECOD) and the cytochrome P450 (P450)
      concentrations in the livers were analyzed. Exposure in the river Elbe increased
      the ECOD activity and the P450 concentration. In a flowthrough basin located in
      the harbor of Hamburg the ECOD activity increased up to 3.5 times, and the P450
      concentration increased slightly by a factor of 1.5. During exposure of the
      golden ide at two Elbe stations upstream and downstream the city of Hamburg,
      levels of P450 in the livers did not change significantly when compared with
      laboratory controls. There was, however, a significant increase of ECOD activity
      between stations Bunthaus (upstream) and Blankenese (downstream). The ECOD
      activity in the livers of golden ide caged downstream were significantly higher
      compared to those at the upstream station. The results presented in this study
      suggest that golden ide can be employed as experimentals for routine measurements
      in limnic habitats using biochemical assays.

PMID- 7523070
TI  - Glutathione-dependent defense in channel catfish (Ictalurus punctatus) and brown
      bullhead (Ameriurus nebulosus).
AB  - Glutathione-dependent defense against xenobiotic toxicity is a multifaceted
      phenomenon that has been well characterized in mammals. This study undertakes a
      comparison of two benthic fish species, the channel catfish and brown bullhead,
      in terms of characteristics of the glutathione system. The channel catfish, a
      species that has seldom been observed to express pollutant-mediated neoplasia in
      field studies, was observed to have significantly higher constitutive levels of
      hepatic total glutathione and reduced glutatione (GSH). Brown bullhead, a species
      that is often observed to express neoplasia in contaminated systems, had
      significantly higher hepatic levels of glutathione disulfide. Furthermore,
      catfish expressed higher levels of activity of the enzymes gamma-glutamylcysteine
      synthetase (GCS), glutathione reductase (GR), and glutathione S-transferase,
      whereas bullhead expressed higher hepatic glutathione peroxidase (GPOX) activity.
      Both species responded to treatment with the redox active quinone, menadione, by
      expressing elevated hepatic content of total glutathione. However, the induction
      response was more rapid and more extensive in catfish compared to that in
      bullhead. This is attributable to the observed interspecific difference in GCS
      activity. Following treatment with the organic peroxide, tert-butyl hydroperoxide
      (t-BOOH), bullhead hepatic glutathione was depleted up to 4 hr post-treatment,
      whereas catfish demonstrated no significant depletion of glutathione in response
      to t-BOOH. The differing responses to t-BOOH are attributable to interspecific
      differences in hepatic GPOX and GR activity. Bullhead, therefore, appear to be
      more susceptible to the effects of GSH arylators and oxidants based upon
      constitutive levels of glutathione, related enzyme activities, and the response
      of this system to model xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523071
TI  - Species differences in brain acetylcholinesterase response to monocrotophos in
      vitro.
AB  - Species-related differences in sensitivity to acute intoxication by
      anticholinesterase (anti-ChE) compounds have been attributed, in large part, to
      differences in the kinetics of inhibition of acetylcholinesterase (AChE: EC
      3.1.1.7) in vitro. The following investigation was designed to determine if
      species-related differences in the sensitivity of brain AChE to inhibition by
      monocrotophos (MCP) could contribute to the interspecies differences in toxicity.
      Brain AChE activity was significantly greater in fish followed by pigeon and rat.
      MCP was found to be a competitive inhibitor of rat, pigeon, and fish brain AChE,
      thereby, altering the Km (Michaelis constant) widely among the species.
      Comparatively, least alterations in Km were observed in fish and maximum in
      pigeon. The Ki (bimolecular inhibition constant) of rat was 1.4- and 3.2-fold
      lower than that of pigeon and fish, respectively. Although fish brain had
      significantly greater AChE activity, it was the least sensitive to MCP
      inhibition. These data suggest that the greater sensitivity of rodent brain AChE
      to inhibition by MCP may contribute to the greater toxicity of MCP in rodents
      than in birds and fishes.

PMID- 7523072
TI  - Kinetics of bioconcentration and clearance of 28 polychlorinated biphenyl
      congeners in zebrafish (Brachydanio rerio).
AB  - Bioconcentration experiments were performed on 28 polychlorinated biphenyl (PCB)
      congeners with NCl = 2 to NCl = 10, evaluating them simultaneously.
      Bioconcentration factors (BCFs) were calculated from the uptake rate constant
      (k1) and the clearance rate constant (k2) as BCF = k1/k2. BCFs on a wet weight
      basis ranged from 7710 to 940,000. They were correlated with octanol-water
      partition coefficients (P). The curvilinear relationship between log BCF and log
      P based upon data covering the log P range 5.06 to 8.18. About a log P of 7.38, a
      range of "optimal lipophilicity," results in highest BCFs for PCBs, above which
      the degree of bioconcentration decreases.

PMID- 7523069
TI  - Fate of a volatile chlorinated solvent in indoor aquatic microcosms: sublethal
      and static exposure to [14C]dichloromethane. Groupe pour l'Etude du Devenir de
      Xenobiotiques dans l'Environnement (GEDEXE).
AB  - The goal of this work was to study the fate of dichloromethane in indoor aquatic
      microcosms after a sublethal and static exposure to simulate the accidental
      contamination of a lenitic ecosystem such as littoral lake zone or a pond. This
      kind of ecosystem is characterized by high productive capacity and rich
      biocoenose, and are usually first affected by acute or chronic pollution.
      Microcosms containing immersed bryophytes (Fontinalis antipyretica), macrophytes
      (Lemna minor, Groenlendia densa, Elodea canadensis), molluscs (Physa fontinalis),
      crustaceans (Daphnia magna), and unicellular green algae (Scenedesmus
      subspicatus) were contaminated with sublethal concentrations of dichloromethane
      or [14C]dichloromethane. The initial mean concentration was 9.9 +/- 3.7 microM.
      The mean concentration exposure for organisms was 4.5 +/- 1.5 microM. The fate of
      14C radioactivity was monitored by measuring the radioactivity of the sediment,
      water, macro- and microorganism, and atmospheric compartments. Radioactivity in
      the water disappeared quickly from the microcosms, most likely as
      [14C]dichloromethane (t1/2 = 5.31 +/- 0.41 days). At the end of the experiments,
      radioactivity was mainly located in the atmosphere, with traces remaining in the
      biomass. Under static conditions, the bioaccumulation of 14C radioactivity from
      the radiolabeled dichloromethane was negligible.

PMID- 7523073
TI  - Characterization of spontaneous MEG rhythms in healthy adults.
AB  - We analyzed spontaneous MEG activity, measured with a whole-head
      neuromagnetometer in 7 healthy, relaxed adults. Rhythmic activity concentrated
      over the rolandic and parieto-occipital regions and contained spectral components
      in the 10 and 20 Hz ranges, each showing distinct reactivity. Sources of the
      rhythmic activity in different frequency ranges were localized within the brain
      and related to the sites of the auditory, visual, and somatosensory projection
      cortices. The sources of the rolandic mu rhythms concentrated in restricted areas
      of 3-5 cm in diameter, close to the hand projection area in the first somatomotor
      cortex. The posterior alpha activity received a significant contribution from the
      vicinity of the parieto-occipital fissure. Combination of spectral analysis,
      reactivity of the rhythms with respect to tasks or stimuli, and source
      localization will allow focusing on well-specified cortical rhythms and assist in
      gaining an understanding of the functional significance of cortical rhythms.

PMID- 7523075
TI  - Auditory ERP components and mismatch negativity in dysphasic children.
AB  - Auditory event-related potentials (ERPs) and especially the mismatch negativity
      component (MMN) were examined in 14 dysphasic and 12 normal children (aged 7-13).
      The ERPs were elicited by sine tone stimuli using the passive oddball paradigm
      and short ISI (350 msec). We measured the peak latency and peak amplitude of MMN
      responses to frequency (500/553 Hz) and duration (50/110 msec or 50/500 msec)
      differences. In the dysphasic group the peak amplitude of the frequency MMN was
      significantly attenuated. The duration MMN showed a significant difference
      between the two groups only for stimuli with highly contrasting values (50/500
      msec). In normal subjects we found a negative correlation between the peak
      latency of the frequency MMN and age. The maturational changes of long-latency
      ERPs were non-significant in dysphasic children. Evidence of differences in
      hemispheric asymmetry between the two groups was observed.

PMID- 7523074
TI  - Tactile mental imagery in sighted persons and in patients suffering from
      peripheral blindness early in life.
AB  - Patterns of cortical activity as measured by scalp-recorded event-related slow
      negative DC potential shifts were recorded in 9 early blind and 23 sighted
      normals while they imagined the feel of textures with the fingertips of one hand.
      All sighted subjects reported to have concomitant visual imagery as well. Hence,
      it was not surprising to observe occipital negative shifts, previously described
      as a sign of occipital visual cortex involvement in visual mental imagery. Though
      having never had visual perception, the blind, too, had occipital negativities.
      Their absolute amplitudes were smaller than in the sighted, not only occipitally
      but also and more pronounced at other areas, particularly frontally where
      amplitudes were even positive. On the hypothesis that the smaller overall
      amplitudes in the blind could obscure topographical differences between groups,
      the relative distribution of negativity across the scalp was assessed, using
      normalized data. Such normalized parameters significantly differed between
      groups, indicating that the occipital potentials of the blind were relatively
      more negative as related to the other scalp areas, than were the occipital
      potentials of the sighted as related to the other scalp areas. This occipital
      finding might indicate a participation of the blind's visually deprived occipital
      cortex in tactile imagery. Second, parietal DC potentials were maximal over the
      hemisphere contralateral to the imaging hand, possibly indicating involvement of
      the contralateral parietal association cortex in tactile imagery. Reasons why
      this was true only for the sighted, are discussed.

PMID- 7523076
TI  - Auditory and colored visual P300 in patients with sequelae of subacute myelo
      optico-neuropathy.
AB  - To study the cognitive function in 13 patients with sequelae of subacute myelo
      optico-neuropathy (SMON), event-related potentials (ERPs) were elicited with
      tones, clicks, and colored visual stimuli in different tasks. P300 latency was
      delayed, and P300 amplitude reduced or absent in 5 patients (38%), although
      neuropsychological assessment for dementia did not differ between patients and 21
      age-matched normal controls. P300 and N200 latencies with the tone/tone auditory
      stimuli and N200 latency with the visual stimuli were significantly delayed, but
      the latencies of early components (N100 and P200) were not delayed. These
      findings suggest that SMON patients may have cognitive dysfunction to a slight
      degree.

PMID- 7523077
TI  - A spatio-temporal dipole model of the readiness potential in humans. I. Finger
      movement.
AB  - Preceding unilateral finger movements readiness potentials (RPs) were recorded in
      9 right-handed subjects. The data are presented as time series, potential maps
      and spatio-temporal dipole models. The latter are interpreted with respect to the
      underlying generators of the RP. Explicit hypotheses about the unilateral or
      bilateral activation of particular sensorimotor areas preceding unilateral
      movements are addressed. The choice for the best spatio-temporal dipole model was
      guided by a test on the orthogonality of the individual residuals and by a priori
      neurophysiological evidence. From the final model it is concluded that the
      initial bilateral symmetrical part of the RP is generated in the posterior walls
      of the precentral gyrus bilaterally, whereas the later lateralized components
      originate from the crown of that same gyrus contralaterally. This confirms and
      extends data from subdural recording, magnetoencephalography (MEG) and EEG.

PMID- 7523079
TI  - A test of brain electrical source analysis (BESA): a simulation study.
AB  - The present report summarizes the results of a simulation study on the accuracy
      of Scherg's implementation of spatio-temporal analysis (BESA) for estimating the
      parameters (wave shape, location, orientation) of the intracranial sources of
      event-related brain potentials (ERPs) recorded from the scalp. In view of the
      subjective factors that might influence a solution, 10 subjects, ranging from
      those with much experience with ERPs and extensive background in the use of BESA
      to those with little experience with BESA and/or no knowledge of ERPs,
      independently analyzed a set of simulated somatosensory ERP data. The simulation
      contained wave forms from 32 electrode sites generated by a combination of 10
      dipole sources. The primary question was how faithfully the different subjects
      would depict the source wave shapes, locations and orientations. Based on the 9
      subjects who were familiar with ERPs, the grand-average cross-correlation
      coefficient between subjects' estimated and actual source wave shapes was 0.89
      (standard deviation (S.D.) = 0.17). The grand-average location error, based upon
      a head diameter of 17 cm, was 1.4 cm (S.D. = 1.0 cm). The grand-average
      orientation error was 24.4 degrees (S.D. = 20 degrees).

PMID- 7523078
TI  - A spatio-temporal dipole model of the readiness potential in humans. II. Foot
      movement.
AB  - Readiness potentials (RP) have been recorded in 9 subjects who performed
      voluntary unilateral plantar flexions with the right or left foot. These show a
      paradoxical ipsilateral dominance. Spatio-temporal dipole models were obtained
      for these data, by iterative parameter estimation. The non-uniqueness of the
      inverse problem leads to several models which describe the data almost equally
      well, and which all pass orthogonality tests for the individual residuals and
      source waves. In these dipole models the ipsilateral preponderance is attributed
      to generators in the contralateral hemisphere, which agrees with results from MEG
      recording. According to these models the main generators of the RP are in the
      primary motor cortex, one bilaterally in its posterior wall and the other in the
      contralateral crown. This agrees with earlier results for finger RPs. However,
      for foot RPs, it was difficult to distinguish individual sub-components in both
      the observed scalp potentials and the estimated temporal activation patterns of
      the dipoles. Some of the presented models include a fronto-central dipole which
      possibly represents activity of the supplementary motor area. It is concluded
      that this finding is at best suggestive and needs further investigation.

PMID- 7523080
TI  - Comments on the "Recommended standards for electroretinograms and visual evoked
      potentials. Report of an IFCN committee" published in the December 1993 issue of
      Electroencephalography and Clinical Neurophysiology.

PMID- 7523081
TI  - SEP topographies elicited by innocuous and noxious sural nerve stimulation. III.
      Dipole source localization analysis.
AB  - The dipole source localization method was used to determine which of the brain
      areas known to be involved in somatosensation are the best candidate generators
      of the somatosensory evoked potential evoked by sural nerve stimulation. The
      ipsilateral central negativity and contralateral frontal positivity which
      occurred between 58 and 90 msec post stimulus (stable period 1) were best
      represented by a single source located in the primary somatosensory cortex (SI).
      The symmetrical central negativity and bilateral frontal positivity which
      occurred between 92 and 120 msec post stimulus (stable period 2) was best
      represented by 3 sources. One of these sources was located in SI and the other 2
      were located bilaterally in either the frontal operculum or near the second
      somatosensory cortex (SII). The widespread negativity whose minimum was located
      in the contralateral fronto-temporal region and which occurred between 135 and
      157 msec post stimulus (stable period 3) was also best represented by 3 sources.
      Two of these sources may be located bilaterally in the hippocampus. We cannot,
      however, eliminate the possibility that multiple sources in the cortex overlying
      the hippocampus (e.g., SII and frontal cortex) are responsible for these
      potentials. At innocuous stimulus levels the third source for stable period 3 was
      located near the vertex, possibly involving the supplementary motor cortex,
      whereas at noxious levels this source appears to be located in the cingulate
      cortex. We were unable to achieve any convincing source localization for the
      widespread positivity which occurred between 178 and 339 msec post stimulus
      (stable periods 4-6). Available evidence suggests that more sources were active
      during this interval than the three we could reliably test under these
      conditions.

PMID- 7523082
TI  - Risk for ABR abnormalities in the nursery.
AB  - The records of 1087 full- and pre-term infants with normal hearing were reviewed
      for auditory brain-stem response (ABR) abnormalities. Subjects were classified
      according to various complications common to the newborn. A logistic regression
      analysis was performed in order to determine the risk of incurring ABR deviations
      associated with specific diagnoses in the nursery. Infants exposed to cocaine in
      utero and those with neurological signs or demonstrable brain anomalies were 4-5
      times more likely to exhibit deviant ABRs. The synergistic effects of selected
      predictor variables further increased the risk for abnormal responses depending
      on gestational age and type of disorder. These results suggest subtle neurologic
      influences persisting at the time of discharge.

PMID- 7523084
TI  - Objective detection of 40 Hz auditory evoked potentials: phase coherence vs.
      magnitude-squared coherence.
AB  - The relative performance of phase coherence (PC) and magnitude-squared coherence
      (MSC) for detection of steady-state evoked potentials was studied using 40 Hz
      auditory evoked potentials (AEPs) in 10 normal human subjects. In addition,
      simulation experiments were carried out to determine the effects of signal
      amplitude and phase variability on detection performance. All simulations showed
      MSC performance to be better than PC performance, with further improvements when
      MSC was supplemented with weighted averaging. However, human 40 Hz AEP data
      showed essentially identical detection performance for PC and MSC, with or
      without weighted averaging. These data support a "phase aggregation" model (at
      least near threshold) over the more usual model in which an AEP signal is added
      to a stationary noise. Human data collected under "no-stimulus" conditions agree
      well with theoretical distributions for both PC and MSC. For equal test time,
      long analysis periods (with less averaging) yielded equal performance to short
      analysis periods (with more averaging), for both PC and MSC.

PMID- 7523083
TI  - Three-channel Lissajous' trajectory of the binaural interaction components in
      human auditory brain-stem evoked potentials.
AB  - The 3-channel Lissajous' trajectory (3-CLT) of the binaural interaction
      components (BI) in auditory brain-stem evoked potentials (ABEPs) was derived from
      17 normally hearing adults by subtracting the response to binaural clicks (B)
      from the algebraic sum of monaural responses (L + R). ABEPs were recorded in
      response to 65 dB nHL, alternating polarity clicks, presented at a rate of
      11/sec. A normative set of BI 3-CLT measures was calculated and compared with the
      corresponding measures of simultaneously recorded, single-channel vertex-left
      mastoid and vertex-neck derivations of BI and of ABEP L + R and B. 3-CLT measures
      included: apex latency, amplitude and orientation, as well as planar segment
      duration and orientation. The results showed 3 apices and associated planar
      segments ("BdII," "Be" and "Bf") in the 3-CLT of BI which corresponded in latency
      to the vertex-mastoid and vertex-neck peaks IIIn, V and VI of ABEP L + R and B.
      These apices corresponded in latency and orientation to apices of the 3-CLT of
      ABEP L + R and ABEP B. This correspondence suggests generators of the BI
      components between the trapezoid body and the inferior colliculus output.
      Durations of BI planar segments were approximately 1.0 msec. Apex amplitudes of
      BI 3-CLT were larger than the respective peak amplitudes of the vertex-mastoid
      and vertex-neck recorded BI, while their intersubject variabilities were
      comparable.

PMID- 7523085
TI  - Whole-head mapping of middle-latency auditory evoked magnetic fields.
AB  - We recorded middle-latency auditory evoked magnetic fields from 9 healthy
      subjects with a 122-channel whole-head SQUID gradiometer. The stimuli were click
      triplets, 2.5 msec in total duration, delivered alternately to the two ears once
      every 333 msec. Contralateral clicks elicited P30m responses in 16 and P50m
      responses in 12 out of 18 hemispheres studied; ipsilateral clicks did so in 7 and
      13 hemispheres, respectively. The field patterns were satisfactorily explained by
      current dipoles in 16 and 4 hemispheres for contra- and ipsilateral P30m, and in
      4 and 10 hemispheres for contra- and ipsilateral P50m. The peak latencies of P30m
      and P50m were not affected by stimulation side. The results show that middle
      latency auditory evoked responses receive a strong contribution from auditory
      cortical structures, and that differences of input latency to cortical auditory
      areas, evaluated from MLAEF latencies, do not explain the latency differences
      seen in late auditory evoked fields to contralateral vs. ipsilateral stimulation.

PMID- 7523086
TI  - Reduction of visual P300 during transient global amnesia.
AB  - Transient global amnesia (TGA) is a syndrome of selective loss of recent memory
      without other neurological deficits. Auditory and visual P300s were recorded
      during and after TGA to investigate the contribution of the short-term memory
      system to P300 generation. The auditory P300 during TGA was comparable to that
      recorded 1 week and 9 months after TGA. In contrast to the auditory modality, the
      visual target P300 was reduced in amplitude during TGA and at 1 week after the
      attack. The P300 to novel visual stimuli was also reduced during TGA. Both target
      and novelty visual P300 recovered by 9 months after TGA. The results support the
      notion that the neuronal networks responsible for P300 generation are modality
      dependent and that brain structures perfused by the posterior circulation are
      involved in visual P300 generation.

PMID- 7523087
TI  - Chemo-somatosensory event-related potentials in response to repetitive painful
      chemical stimulation of the nasal mucosa.
AB  - The aim of the study was to investigate how chemo-somatosensory event-related
      potentials (CSSERPs) and pain ratings are modified by repetitive painful
      stimulation of the nasal mucosa (58% v/v CO2, 200 msec duration). Twenty-two
      subjects performed 3 experiments during which trains of stimuli were applied. The
      interstimulus interval (ISI) between stimuli was constant for each experiment,
      but varied between experiments (8, 4, and 2 sec). CSSERPs were obtained from 5
      positions (Fz, C3, Cz, C4, and Pz). The subjects not only rated the overall
      perceived intensities but also reported the quality of the stimuli. At an ISI of
      8 sec estimates decreased and only stinging sensations were reported. In
      contrast, at an interval of 2 sec estimates increased being accompanied by the
      buildup of burning pain. This phenomenon was interpreted in terms of the
      superposition of first (sharp and stinging pain: A delta fibers) and second pain
      (dull and burning pain: C fibers), respectively. However, given the special
      circumstances of short ISIs CSSERP amplitudes decreased the more the shorter the
      ISI was. In line with previous investigations it is hypothesised that CSSERPs
      predominantly reflect nociceptive information transmitted via A delta fibers.

PMID- 7523089
TI  - Mass-action view of single-cell responses to stimulation of the receptive field
      and/or beyond: exemplification with data from the rabbit primary visual cortex.
AB  - Whereas single cells in the visual cortex prefer moving light bars, mass-action
      responses are evoked better by diffuse luminance changes. This discrepancy was
      investigated by quantitatively comparing the response properties of individual
      cells with those of a representative group of cells. The latter responses were
      derived from the single-cell responses, which were obtained from recording in the
      rabbit. These quantitative estimates of mean responses resolve the discrepancy
      between the single-cell domain and the mass-action domain: from the single-cell
      point of view, a properly oriented moving-bar stimulus is much more effective
      than a diffuse-light stimulus. The corresponding mass-action response to one
      common moving-bar stimulus, however, is as small as the mean response to a
      diffuse-light stimulus (which may even be presented at retinotopically non
      corresponding sites). The peak intensities of these mass responses are even much
      stronger with the diffuse-light stimuli. The same conclusions are valid for the
      cat, as could be verified from published data. The restrictions of the local
      receptive field concept that may be implied by the mass-action view of cortical
      activity and the potential functional relevance of mass activities are discussed.

PMID- 7523090
TI  - High-rate sequential sampling of auditory brain-stem and somatosensory evoked
      responses in hypoxia.
AB  - We developed a high-rate sequential recording technique that allowed simultaneous
      measurements of both auditory brain-stem response (ABR) and somatosensory evoked
      potential (SEP) every 10 sec. Using this method, a transient increase in
      amplitude of all the ABR and SEP components in response to hypoxia in dogs could
      be detected. The increase in amplitude preceded the prolongation of latency. Our
      study showed that there were successive changes of evoked potentials in response
      to hypoxia. A transient increase in amplitude is the first to occur, followed by
      a latency prolongation and an amplitude decrease for both ABRs and SEPs.

PMID- 7523088
TI  - Local estimate of surface Laplacian derivation on a realistically shaped scalp
      surface and its performance on noisy data.
AB  - A new implementation of the surface Laplacian derivation (SLD) method is
      described which reconstructs a realistically shaped, local scalp surface geometry
      using measured electrode positions, generates a local spectral-interpolated
      potential distribution function, and estimates the surface Laplacian values
      through a local planar parametric space using a stable numerical method combining
      Taylor expansions with the least-squares technique. The implementation is
      modified for efficient repeated SLD operations on a time series. Examples are
      shown of applications to evoked potential data. The resolving power of the SLD is
      examined as a function of the spatial signal-to-noise (SNR) ratio. The analysis
      suggests that the Laplacian is effective when the spatial SNR is greater than 3.
      It is shown that spatial low-pass filtering with a Gaussian filter can be used to
      reduce the effect of noise and recover useful signal if the noise is spatially
      incoherent.

PMID- 7523091
TI  - Differential sensitivity to rotation measured on potentials evoked by electrical
      stimulation of the guinea-pig ear.
AB  - Responses to electrical stimulation of the ear applied between round-window and
      vertex electrodes were recorded in awake guinea-pigs from the same electrodes or
      from separate vertex/mastoid subdermal needle electrodes. They were averaged
      during opposite phases of sinusoidal rotation or before and after constant
      velocity rotation. In both cases the responses were subtracted from each other
      and yielded differential per- or post-rotatory "electrovestibular" responses. For
      comparison, responses were also recorded in the same animals and conditions of
      electrical stimulation during silence and during silence and during presentation
      of a broad-band noise. The difference yielded "electroacoustic" responses. In
      round-window records, electrovestibular and electroacoustic responses presented
      typical compound nerve action potential patterns. Electrovestibular responses
      could be recorded for head angular velocities as low as 3 degrees sec-1 at 0.1
      Hz. Response amplitude showed a logarithmic relation to head velocity. Changes in
      amplitude, as a function of time after rotation, were comparable to those
      reported for vestibular nerve fibre responses. In vertex/mastoid records,
      electroacoustic responses presented a sequence of peaks similar to the click
      evoked auditory brain-stem responses, and electrovestibular responses presented
      two peaks, presumably representing contributions of central vestibular
      structures. Such "electrovestibulography" permits the study of an individual ear
      and makes available to the investigator a large range of vestibular stimulation
      conditions.

PMID- 7523092
TI  - A high-intensity, goggle-mounted flash stimulator for short-latency visual evoked
      potentials.
AB  - The few studies that have been done on short-latency, subcortical visual evoked
      potentials (SVEPs) have all used stroboscopic flashes as the evoking stimulus.
      The dimensions of the stimulator, the acoustical artifacts and the photic spread
      to the examination room limited the use of SVEPs to research laboratories. With
      the advent of high-efficiency light-emitting diodes (LEDs), high-intensity
      flashes can now be generated from goggle-mounted LEDs. In this study, a goggle
      mounted high-intensity stimulator was constructed and its flashes used to evoke
      SVEPs. The reproducibility of SVEPs across subjects and the ease of using the
      high-intensity LED flash stimulator make them a promising candidate for testing
      subcortical visual pathway function in the operating room.

PMID- 7523093
TI  - Synergistic effects of parathyroid hormone and 1,25-dihydroxyvitamin D3 on
      proliferation and vitamin D receptor expression of rat growth cartilage cells.
AB  - We investigated possible interaction of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]
      and PTH on: 1) proliferation (monolayer culture) and colony formation (agarose
      stabilized suspension cultures); 2) expression of 1,25-(OH)2D3 receptor (VDR);
      and 3) cAMP response to PTH, using primary cultures of chondrocytes from rat
      tibia proximal epiphysis. 1 alpha,25-(OH)2D3 stereospecifically stimulated DNA
      synthesis, cell counts, and colony formation at low concentration (10(-12) M).
      Within 6 h bovine PTH (bPTH)(1-34), human PTH (hPTH)(28-48) (10(-10) M),
      (Bu)2cAMP (1-2 mM), and 12-O-tetradecanoyl-13-acetate (10(-8) M) increased
      [3H]thymidine incorporation in the absence and presence of 1,25-(OH)2D3. Both PTH
      fragments also stimulated chondrocyte growth and colony formation in a Ca
      dependent fashion. Prolonged exposure to bPTH(1-34) or hPTH(28-48) did not affect
      baseline DNA synthesis but increased the stimulatory effect of 1,25-(OH)2D3. This
      increase was inhibited in the presence of H7 (inhibition of PKC) or the
      monoclonal hPTH(1-38) antibody A1-70. In subconfluent chondrocyte cultures VDR
      was up-regulated by bPTH(1-34) and hPTH(28-48) (10(-10) M) or activators of
      protein kinase C (PKC), but not by (Bu)2cAMP. It was blocked by cycloheximide and
      actinomycin D and persisted in the presence of Ca-channel blockers. Inhibition of
      PKC by H7 also blocked the effect of bPTH(1-34) on VDR. The cAMP response to
      bPTH(1-34) was not affected by 1,25-(OH)2D3. We conclude that: 1) DNA synthesis,
      cell proliferation, and colony formation in chondrocyte monolayer or suspension
      cultures is increased by aminoterminal and midregional PTH fragments and by cAMP
      analogs in a Ca- dependent fashion; 2) bPTH(1-34) and hPTH(28-48) up-regulate VDR
      by cAMP-independent, PKC-dependent steps requiring transcriptional and
      translational processes; both PTH fragments also amplify the effect of 1,25
      (OH)2D3 on DNA synthesis; and 3) no difference is found between the bPTH(1-34)
      and hPTH(28-48) fragments with respect to chondrocyte proliferation and VDR up
      regulation, although the two differ with respect to stimulation of cAMP
      production.

PMID- 7523094
TI  - Human insulin-like growth factor-binding protein-1 (hIGFBP-1) in transgenic mice:
      characterization and insights into the regulation of IGFBP-1 expression.
AB  - Three hemizygous transgenic (Tg) mouse lines were generated with a fusion gene
      composed of the mouse metallothionein promoter (mMT-I) and a full-length human
      insulin-like growth factor binding protein-1 (hIGFBP-1) complementary DNA that
      was truncated in its 3'-untranslated region. Despite high serum hIGFBP-1 levels
      (120-2570 micrograms/liter) before puberty in two of these lines, no significant
      alterations were observed in somatic growth, nor were marked alterations noted in
      fasting or random serum glucose or in the response of young adult Tg mice to ip
      glucose. The transgene was expressed in a number of tissues from each line, but
      liver was a significant site of transgene expression in only one line.
      Unexpectedly, liver hIGFBP-1 messenger RNA (mRNA) expression in this line was
      regulated in fashion similar to the native liver IGFBP-1 mRNA: 1) its abundance
      waned with advancing postnatal age and became minimal in early adult life,
      despite continuous zinc supplementation to stimulate its transcription; and 2)
      fasting increased its abundance 3- to 4.3-fold. The decline in transgene
      expression with aging was not due to a deletion, rearrangement, or a change in
      the methylation of liver transgene DNA. Transcriptional mechanisms also were not
      likely to account for the observed regulation of the transgene mRNA, because
      liver expression of the mMT-I gene, which shares identical genomic 5'-regulatory
      elements with the transgene, was not similarly altered by aging or fasting.
      Because cycloheximide (CHX) treatment of cultured rat H4IIE cells has been shown
      to prolong IGFBP-1 mRNA half-life while decreasing its transcription, Tg mice
      were treated with CHX to test the possibility that instability of the liver
      transgene mRNA influenced its abundance. After CHX and under conditions of
      chronic zinc supplementation, liver transgene mRNA abundance increased in
      parallel with that of the native IGFBP-1 mRNA. Although CHX is known to activate
      mMT-I transcription by mechanisms involving the 5'-regulatory regions contained
      in the transgene, CHX-induced transcription only in part accounted for the
      increase in liver transgene mRNA, because CHX induced an earlier and greater
      increase in liver transgene mRNA than in mMT-I mRNA. Taken together, these data
      indicate that both transgene and native IGFBP-1 liver mRNA are regulated by
      factors that alter mRNA stability. The finding that native liver IGFBP-1 mRNA
      abundance is influenced by transgene expression further supports the concept that
      both mRNAs share some common mechanisms of regulation.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7523095
TI  - Glucocorticoid regulation of an insulin-like growth factor-binding protein-4
      protease produced by a rat neuronal cell line.
AB  - Insulin-like growth factor-binding protein-4 (IGFBP-4) is expressed in distinct
      regions in the rodent brain from the perinatal period into adulthood and is
      postulated to modulate the action of the insulin-like growth factors (IGFs) in
      vivo. This study was initiated to examine the regulation of IGF-binding protein-4
      (IGFBP-4) in B104 cells, a rat neuronal cell line in which IGFBP-4 is the
      predominant secreted IGFBP. Exposure of B104 monolayer cultures to dexamethasone
      reduced native IGFBP-4 abundance to less than 10% of that in control medium by 48
      h. Immunoblots showed that the decline in intact 24-kilodalton IGFBP-4 was
      accompanied by an increase in a 16-kilodalton immunoreactive fragment. In
      addition, IGFBP-4 proteolytic activity in medium was increased after exposure of
      the cells to dexamethasone. The protease was calcium dependent and appeared to be
      of the serine protease class, because activity could be inhibited by
      phenylmethylsulfonylfluoride and aprotinin, but not antipain, leupeptin, or
      pepstatin. Although the proteolytically modified IGFBP-4 retained the ability to
      bind IGFs, the affinities were approximately 13- and 20-fold lower for IGF-I and
      IGF-II, respectively. These data indicate that B104 cells produce an IGFBP-4
      protease that is regulated by glucocorticoids. The actions of this protease
      reduce the affinity of IGFBP-4 for the IGFs without abolishing binding. Because
      both the IGFs and glucocorticoids have important roles in brain development, it
      is possible that some glucocorticoid actions in the brain could be mediated by
      proteolysis of IGFBP-4, which, in turn, would alter IGF action.

PMID- 7523098
TI  - Identification, localization, and regulation of insulin-like growth factor
      binding proteins and their messenger ribonucleic acids in the newborn rat
      olfactory bulb.
AB  - Insulin-like growth factor binding proteins (IGFBPs) have been identified in most
      tissues, including the central nervous system, where the major IGFBPs have been
      localized. The regulation and roles of IGFBPs in IGF action in the developing
      brain remain unclear. In this study we examined the expression and anatomical
      distribution of IGFBP messenger RNAs (mRNAs) in the newborn rat olfactory bulb
      (OB) during the first postnatal week. We used our recently developed newborn rat
      OB organ culture system, which emulates the first week of in vivo development, to
      identify and characterize expressed and secreted IGFBPs and to determine the role
      of the local growth factors IGF-I and basic fibroblast growth factor (bFGF) in
      their regulation. Postnatal day 1 rat OBs were cultured serum free for 6 days in
      the absence or presence of IGF-I (150 ng/ml) and bFGF (25 ng/ml), alone or in
      combination, as previously shown by us to maintain morphology and differentiation
      of neuronal and glial cells. Conditioned medium was subjected to sodium dodecyl
      sulfate polyacrylamide gel electrophoresis and Western ligand blotting using
      [125I]IGF-I, and IGFBPs were characterized by immunoprecipitation. Western ligand
      blotting of conditioned medium revealed two bands at 24 kilodaltons (kDa) and 30
      kDa and a doublet at 38-42 kDa. All bands were enhanced by IGF-I treatment,
      whereas bFGF enhanced the 24-kDa and 30-kDa bands only. In combination, IGF-I and
      bFGF enhanced all four bands above that seen with either growth factor alone.
      Total RNA was extracted from fresh day 1, day 6, and cultured OBs for Northern
      blotting using complementary DNA probes for IGFBP-2, -3, -4, and -5. In fresh day
      1 OBs, mRNA was detected for IGFBP-2, -4, and -5, but not for IGFBP-3. In fresh
      day 6 OBs IGFBP-2 mRNA was more abundant, whereas IGFBP-4 mRNA showed lower
      expression than at day 1, and IGFBP-5 mRNA was similarly expressed. When day 1
      OBs were cultured for 6 days, mRNA was also readily detected for IGFBP-2, -4, and
      -5, but not for IGFBP-3. All detected mRNA species were enhanced by IGF-I. Basic
      FGF enhanced IGFBP-2 mRNA whether alone or in combination with IGF-I and enhanced
      only IGFBP-4 mRNA when given alone. IGFBP-5 mRNA was not affected by bFGF alone,
      but its enhancement by IGF-I was attenuated by bFGF. Sites of transcription of
      IGFBP and IGF-I mRNAs were located by in situ hybridization in both fresh and
      cultured bulbs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523097
TI  - Induction of galanin gene expression in gonadotropin-releasing hormone neurons
      with puberty in the rat.
AB  - The onset of puberty reflects the developmental activation of GnRH neurons whose
      secretory activity awakens the reproductive axis; however, the cellular
      mechanisms involved in this activational process remain poorly understood. GnRH
      neurons coexpress the neuropeptide galanin, and we have previously shown that
      galanin's level of coexpression is linked to the activity state of GnRH neurons.
      We theorized that altered expression of galanin by GnRH neurons may be an
      important mechanism related to activation of GnRH neurons at puberty. We examined
      two hypotheses related to this idea. First, we tested the hypothesis that
      expression of galanin messenger RNA (mRNA) in GnRH neurons is induced across the
      transition from prepubertal to adult life in the rat. To accomplish this, we used
      double label in situ hybridization and image analysis to compare cellular levels
      of galanin mRNA in GnRH neurons between groups of prepubertal and adult male and
      female rats. Levels of galanin mRNA within GnRH neurons increased significantly
      across puberty in both sexes. In females, galanin mRNA signal in GnRH neurons
      increased approximately 8-fold, whereas in males, cellular galanin mRNA signal
      levels increased about 2-fold. The number of identifiable GnRH neurons was not
      significantly different among the experimental groups. Next, we examined the
      hypothesis that pubertal induction of galanin mRNA in GnRH neurons reflects the
      activational effects of gonadal hormones associated with the onset of puberty. To
      test this, we killed groups of prepubertal male and female rats together with
      adult male and female animals that had been either castrated or sham castrated at
      a prepubertal age. In animals that had been prepubertally castrated, no
      developmental increase in galanin mRNA in GnRH neurons was observed, whereas in
      sham-castrated animals, levels of galanin mRNA in GnRH neurons were again shown
      to be higher in adult compared to prepubertal animals of both sexes, as had been
      demonstrated in the first experiment. We conclude that galanin message expression
      in GnRH neurons is induced during the transition from the juvenile to the adult
      state through a gonad-dependent process. This developmental increase in galanin
      gene expression is one mechanism by which the capacity for the synthesis and
      secretion of galanin by GnRH neurons may be enhanced, which, in turn, could
      facilitate the functional activity of GnRH neurons and amplify their trophic
      effect on the pituitary.

PMID- 7523099
TI  - Role of the extracellular regions of the parathyroid hormone (PTH)/PTH-related
      peptide receptor in hormone binding.
AB  - The PTH/PTH-related peptide receptor is a member of a newly discovered family of
      G-protein-coupled receptors. Strikingly conserved features among these receptors
      include the positioning of eight extracellular cysteines and several other
      residues that are located predominantly within the membrane-embedded region.
      Deletion mutants or receptors with point mutations of the highly conserved
      cysteine residues were transiently expressed in COS-7 cells to evaluate PTH
      binding and PTH-stimulated cAMP production. Deletion of residues 61-105, which
      are encoded by exon E2 in the PTH/PTH-related peptide receptor gene, did not
      affect receptor function. An epitope derived from Haemophilus influenza
      hemagglutinin was, therefore, introduced into this portion of most receptors to
      allow the independent assessment of cell surface expression. PTH binding capacity
      was not reduced by the deletion of residues 258-278 in the first extracellular
      loop. Receptors with deletion of either residues 31-47 in the amino-terminal
      extension or residues 431-440 in the third extracellular loop failed to bind PTH,
      although expression of the receptor on the cell surface was only marginally
      reduced. Most other receptor mutants, including those in which each of the six
      cysteines in the amino-terminus was replaced by serines, failed to be processed
      and/or expressed appropriately, whereas the substitution of cysteine-281 or -351
      had a less severe effect. The combined replacement of both cysteines
      concomitantly increased PTH binding and cell surface expression, suggesting the
      formation of a disulfide bond between these two residues. Our data indicate that
      residues near the amino-terminus and within the third extracellular loop are
      necessary for ligand binding, whereas more than 25% of the receptor's
      extracellular region appears not to be involved.

PMID- 7523096
TI  - Human fibroblasts secrete a serine protease that cleaves insulin-like growth
      factor-binding protein-5.
AB  - We have previously reported the presence of proteolytic activity in conditioned
      medium from human fibroblast cultures that cleaves insulin-like growth factor
      binding protein-5 (IGFBP-5) into non-IGF-I-binding fragments. Coincubation of IGF
      I or IGF-II and IGFBP-5 with fibroblast cultures decreased proteolysis. The
      protease was purified by heparin-Sepharose affinity chromatography. The purified
      protease cleaved IGFBP-5 into 22-, 20-, and 17-kilodalton non-IGF-I-binding
      fragments. Protease inhibitor profiles obtained using partially purified enzyme
      showed that it was a calcium-dependent serine protease. After chelation with
      EDTA, the activity could only be partially restored with zinc, indicating that it
      was probably not a metalloprotease. The protease was specific for IGFBP-5 and did
      not cleave pure IGFBP-1, -2, -3, or -4. IGF-I and IGF-II caused minimal
      inhibition of proteolysis in vitro. This suggests that the IGF-I-induced increase
      in IGFBP-5 in fibroblast medium is only partially due to direct protease
      inhibition. Heparin, antithrombin-III (AT-III), and heparin cofactor-II had
      inhibitory activity, and heparin potentiated the activity of AT-III. Synthetic
      peptides, that contained the active sites of AT-III and alpha 1-antichymotrypsin,
      were also inhibitory. Peptides containing sequences found in two basic regions of
      IGFBP-5 were tested, and one had inhibitory activity. In summary, fibroblasts
      secrete a serine protease that cleaves IGFBP-5 and is specific for this form of
      IGFBP. The protease has properties that are similar to kallikreins, a family of
      serine proteases that is known to cleave epidermal and nerve growth factor
      binding proteins.

PMID- 7523101
TI  - Nitric oxide synthesized by gonadotropin-releasing hormone neurons is a mediator
      of N-methyl-D-aspartate (NMDA)-induced GnRH secretion.
AB  - N-Methyl-D-aspartate (NMDA) directly stimulates gonadotropin-releasing hormone
      (GnRH) neurons to secrete GnRH. It is not known if this stimulatory effect of
      NMDA is mediated by NO. Northern blot analysis of the immortalized hypothalamic
      GnRH neuronal cells (GT1-1) mRNA with a neuronal NOS cDNA revealed this clonal
      cell line expressed neuronal NOS transcripts as a single 10.5-kb band. Immunoblot
      analysis of GT1-1 proteins with anti-neuronal NOS serum showed that the GT1-1
      cells contain neuronal NOS. GT1-1 cells were used to study the effects of NO and
      NMDA on GnRH release. L-Arginine (10(-2) M), a precursor of NO enhances basal
      GnRH secretion. Both oxyhemoglobin (Hb)(10(-6)-10(-4) M), a NO scavenger and N
      omega-nitro-L-arginine (NNA)(10(-3),10(-2) M), a NOS inhibitor and inactivator
      block basal as well as NMDA-induced GnRH release. Sodium nitroprusside (SNP) (10(
      4), 10(-3) M), a NO donor stimulates GnRH release, an effect inhibited by Hb.
      Incubation of GT1-1 cells in Ca(2+)-free medium abolished the stimulatory effect
      of NMDA on GnRH release. In contrast, incubation in medium with increasing
      concentrations of Ca2+ enhances basal GnRH release as well as augments NMDA
      mediated GnRH release. The results demonstrate that L-arginine-NO pathway is
      functional in the GT1-1 cells and an increase in intracellular Ca2+ [Ca2+]i
      following NMDA receptor activation activates NOS to generate NO. We conclude that
      endogenous NO mediates, at least in part, basal as well as NMDA-stimulated GnRH
      release and may play a role as an intercellular messenger in synchronizing
      pulsatile GnRH release.

PMID- 7523100
TI  - Role of lipoxygenase metabolites of arachidonic acid in the regulation of
      adrenocorticotropin secretion by perifused rat anterior pituitary cells.
AB  - Arachidonic acid metabolites have been implicated in the regulation of ACTH
      secretion. To define further which eicosanoid(s) is primarily involved, we
      examined the effects of both inhibitors of the three arachidonate metabolic
      pathways (cyclooxygenase, lipoxygenase, and epoxygenase) and specific eicosanoid
      products on ACTH secretion by rat pituitary corticotrophs in a microperifusion
      system. CRF stimulates sustained ACTH release that is mediated by protein kinase
      A-induced extracellular Ca2+ (Cae2+) influx via L-type voltage-sensitive calcium
      channels (VSCC). Arginine vasopressin (AVP) stimulates an initial spike phase of
      ACTH release that presumably is mediated by inositol 1,4,5-trisphosphate-induced
      intracellular Ca2+ (Cai2+) release, followed by a sustained plateau phase of ACTH
      release that is mediated by protein kinase-C-induced Cae2+ influx via L-type
      VSCC. Pretreatment for 15 min with the lipoxygenase inhibitor
      nordihydroguaiaretic acid (NDGA; 50 microM), but not the cyclooxygenase inhibitor
      indomethacin (10 microM) or the epoxygenase inhibitor SKF525A (100 microM)
      inhibited the sustained response to CRF by 48% and the initial spike response to
      AVP by 38%. NDGA-induced inhibition was not reversed by indomethacin or SKF525A,
      alone or in combination, precluding arachidonate shunting into other pathways.
      However, the results suggested that epoxygenase metabolites may have a minor
      stimulatory and cyclooxygenase metabolites may have a minor inhibitory effect on
      ACTH secretion. Preexposure to NDGA suppressed by 43% the sustained response to 8
      bromo-cAMP, which directly activates protein kinase-A; by 57% the sustained
      response to dioctanolglycerol, which directly activates protein kinase-C; and by
      59% the spike-type response to ionomycin, which releases Cai2+ by an inositol
      1,4,5-trisphosphate-independent mechanism. These results suggest that NDGA either
      inhibits the production of a lipoxygenase metabolite involved in Cae2+ influx
      and/or Cai2+ release or acts other than by inhibiting lipoxygenase, such as by
      directly blocking membrane transport of Cae2+. The three major lipoxygenase
      metabolites tested, 5(S)-, 12(S)-, and 15(S)-hydroxyeicosatetraenoic acid (HETE),
      all stimulated sustained ACTH release in a dose-dependent manner. At a
      concentration of 2 microM, 12(S)-HETE was 4.7 and 2.5 times more potent than 5(S)
      and 15(S)-HETE, respectively, and completely reversed NDGA inhibition of both
      CRF- and AVP-stimulated ACTH secretion. The ACTH-releasing activity of 12(S)-HETE
      was inhibited 26% by removing Cae2+ and 54% by both removing Cae2+ and depleting
      Cai2+, indicating either that 12(S)-HETE facilitates transmembrane Ca2+ transfer
      or that increased cytosolic Ca2+ is necessary for 12(S)-HETE's action.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7523102
TI  - Sources of lead exposure in Mexico City.
AB  - Many countries, including Mexico, are facing a largely unrecognized epidemic of
      low-level lead poisoning. Mexico is the sixth largest lead-producing country in
      the world, and 40% of its production is used locally in different industrial
      processes that cause lead contamination of the environment. The major sources and
      pathways of lead exposure among the Mexican population are gasoline emissions,
      lead-glazed ceramics, leaded paint, and lead in canned foods and beverages. In
      this paper we present evidence for the presence of lead in different
      environmental media and its impact on blood lead levels of the Mexican
      population. Although during the last few years important measures have been
      implemented to decrease lead exposure, our findings suggest that lead poisoning
      is still an important problem in Mexico. There is an urgent need for regulatory
      policies that implement stricter control to protect the Mexican population. There
      is also a need to develop adequate programs to reduce the lead burden and the
      associated health effects in the population that has been chronically exposed.

PMID- 7523103
TI  - Assessment of developmental toxicity: neuropsychological batteries.
AB  - Assessment of change in behavioral functioning in children as a function of
      neurotoxicity is not a trivial undertaking. Psychological tests, widely (though
      erroneously) considered to be the "gold standard" for measurement of behavior in
      humans, are not adequate for the task; they tap the structure of cognition, not
      the behavioral repertoire, and cannot (alone) address developmental change.
      Comprehensive neurobehavioral assessment must be undertaken within a
      multidisciplinary assessment strategy incorporating knowledge of brain and brain
      development, cognitive processes and their development, brain-behavior
      relationships, and detailed knowledge of neurotoxicants, their action and the
      exposure thereto. Initial assessment batteries must be adequately broad ranging
      and must incorporate strategies and data for evaluating the impact of predictable
      nonbrain variables; they must also be cost efficient to respond to the realities
      of funding and the exigencies of field testing. Measures of neuropsychological
      outcome are optimally characterized as they relate to behavioral domains
      specified in terms of the competencies of infants and children of different ages;
      relevant information is derived from demographic, socioeconomic, medical,
      developmental, and educational sources, as well as from detailed observational
      data and performance on psychological tests. Two levels of assessment are
      proposed.

PMID- 7523106
TI  - Rapid method for isolating detergent-insoluble outer membrane proteins from
      Pseudomonas aeruginosa.
AB  - The present study compares two techniques for isolating outer membrane proteins
      (OMPs) of Pseudomonas aeruginosa, Method A - selective solubilization with sodium
      lauryl sarcosinate, and Method B - isopycnic sucrose gradient centrifugation,
      using three criteria: the amount of proteins obtained, polypeptide patterns after
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and their practical
      aspects. Method A appears to be superior to Method B. It yields a higher outer
      membrane protein content and a similar polypeptide pattern as Method B, but is
      more rapid and less cumbersome.

PMID- 7523107
TI  - Characterization of the acute phase serum protein response in pigs.
AB  - Acute inflammation was induced in pigs using a single subcutaneous turpentine
      injection. The acute phase serum protein response was analyzed using crossed
      immunoelectrophoresis and immunodiffusion. The concentration of C reactive
      protein and haptoglobin increases 5-7 times 48 h after the injection, whereas the
      concentration of an alpha 2-globulin, named pig major acute phase protein (pig
      MAP), increases at least 15-fold. A molecular mass of 115 kDa for pig-MAP was
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This
      protein did not crossreact with antisera to human hemopexin, ceruloplasmin, H
      kininogen and complement factor C3. Albumin and alpha-lipoprotein were negative
      acute phase proteins because their concentration significantly decreased during
      inflammation. Finally, the concentration of alpha 1-acid glycoprotein, fetuin,
      alpha 1-protease inhibitor, transferrin and alpha 2-macroglobulins, as well as
      total proteins, did not change significantly during inflammation.

PMID- 7523108
TI  - Separation and sequencing of familiar and novel murine proteins using preparative
      two-dimensional gel electrophoresis.
AB  - Strategies are needed for rapid protein isolation in order to identify disease
      related proteins and facilitate the design of oligonucleotides for further
      molecular inquiry. In our laboratory, C3H10T1/2 murine fibroblasts have been
      found to express a variety of proteins in various subcellular fractions which are
      relevant to experimental transformation and carcinogenesis. Preparative two
      dimensional polyacrylamide gel electrophoresis (2-D PAGE) procedures were
      developed to identify major cytoplasmic proteins by electroblotting and
      microsequencing. Isoelectric focusing tube gels were enlarged to 6 mm ID to
      accommodate larger protein loads at 0.5 to 2 mg protein. Separated proteins were
      electrotransferred from 6 mm thick slab gels onto 0.22 mu polyvinylidene
      difluoride membranes. Nearly 100 prominent blotted proteins were stained with
      Coomassie Brilliant Blue between pI 4.5-7.0 and 18-106 kDa and, of these, 27
      prominent and well-resolved proteins were selected for sequencing. Sequences of
      14 to 24 amino acid residues in length were obtained from 11 proteins which were
      identified from computerized databases. Some of these identified proteins had
      structural or enzymatic functions while others had only recently been discovered,
      including a newly reported Hsp 70 class member and a novel calcium-binding
      protein, reticulocalbin. The new heat shock protein has a molecular mass of 75
      kDa and has been designated as Grp75, PBP74, CSA or p66mot-1 in mice and humans
      with purported roles in transformation and antigen processing. Reticulocalbin is
      an endoplasmic reticular protein which contains six domains of the EF-hand motif
      associated with high-affinity calcium-binding proteins. It may be involved in
      protein transport and luminal protein processing. In addition, sequences of 5 to
      11 residues in length were also obtained from six other unidentified proteins.
      Thus, we have found that preparative 2-D PAGE serves as a powerful one-step
      purification method for protein isolation and characterization from an important
      in vitro murine model for the study of carcinogenesis.

PMID- 7523105
TI  - Safety aspects of non-depolarizing neuromuscular blocking agents with special
      reference to rocuronium bromide.
AB  - The safety of neuromuscular relaxants can be assessed according to their
      cardiovascular and autonomic effects, their liability to release histamine, their
      tendency to cause anaphylactic/anaphylactoid reactions, their effect on
      cholinesterase, on intra-ocular and intracranial pressure, their tendency to
      cumulation and their reversibility. Any adverse effects of metabolites are also
      potential problems. Against these standards, rocuronium may have some mild
      vagolytic activity. Apart from that, its safety profile is indistinguishable from
      that of vecuronium.

PMID- 7523104
TI  - Regulation of antioxidant enzymes in lung after oxidant injury.
AB  - Studies have implicated active oxygen species (AOS) in the pathogenesis of
      various lung diseases. Many chemical and physical agents in the environment are
      potent generators of AOS, including ozone, hyperoxia, mineral dusts, paraquat,
      etc. These agents produce AOS by different mechanisms, but frequently the lung is
      the primary target of toxicity, and exposure results in damage to lung tissue to
      varying degrees. The lung has developed defenses to AOS-mediated damage, which
      include antioxidant enzymes, the superoxide dismutases [copper-zinc (CuZnSOD) and
      manganese-containing (MnSOD)], catalase, and glutathione peroxidase (GPX). In
      this review, antioxidant defenses to environmental stresses in the lung as well
      as in isolated pulmonary cells following exposure to a number of different
      oxidants, are summarized. Each oxidant appears to induce a different pattern of
      antioxidant enzyme response in the lung, although some common trends, i.e.,
      induction of MnSOD following oxidants inducing inflammation or pulmonary
      fibrosis, in responses to oxidants occur. Responses may vary between the
      different cell types in the lung as a function of cell-cycle or other factors.
      Increases in MnSOD mRNA or immunoreactive protein in response to certain oxidants
      may serve as a biomarker of AOS-mediated damage in the lung.

PMID- 7523109
TI  - Identification of pro-thymocytes in murine fetal blood: T lineage commitment can
      precede thymus colonization.
AB  - Phenotype and commitment of thymus-colonizing precursors are unknown. Here we
      report the identification of T lineage-committed precursors (designated
      prothymocytes) in murine fetal blood at day 15.5 of development. Fetal blood pro
      thymocytes are Thy-1+c-kit(low)CD3- in contrast to fetal blood-derived
      pluripotent hematopoietic progenitors which are Thy-1-c-kit+. Upon transfer into
      the thymus, fetal blood pro-thymocytes generate a single wave of CD4+CD8+
      thymocytes and subsequently mature TCR alpha beta+ peripheral T cells. However,
      fetal blood pro-thymocytes lack multipotent progenitor potential since they fail
      to reconstitute B lymphocytes and myeloid and erythroid lineages. In contrast, T
      and B lymphocytes as well as myeloid and erythroid lineages are reconstituted
      from fetal blood-derived pluripotent progenitors. Pro-thymocytes are equally
      present in peripheral blood of athymic fetal mice, suggesting that this novel
      precursor population is T lineage-committed prior to thymus colonization and
      represents the earliest T lineage precursor identified.

PMID- 7523110
TI  - Activation of the phosphatase activity of human cdc25A by a cdk2-cyclin E
      dependent phosphorylation at the G1/S transition.
AB  - Progression through the cell cycle is monitored at two major points: during the
      G1/S and the G2/M transitions. In most cells, the G2/M transition is regulated by
      the timing of p34cdc2 dephosphorylation which results in the activation of the
      kinase activity of the cdc2-cyclin B complex. The timing of p34cdc2
      dephosphorylation is determined by the balance between the activity of the kinase
      that phosphorylates p34cdc2 (wee1 in human cells) and the opposing phosphatase
      (cdc25C). Both enzymes are regulated and it has been shown that cdc25C is
      phosphorylated and activated by the cdc2-cyclin B complex. This creates a
      positive feed-back loop providing a switch used to control the onset of mitosis.
      Here, we show that another member of the human cdc25 family, cdc25A, undergoes
      phosphorylation during S phase, resulting in an increase of its phosphatase
      activity. The phosphorylation of cdc25A is dependent on the activity of the cdc2
      cyclin E kinase. Microinjection of anti-cdc25A antibodies into G1 cells blocks
      entry into S phase. These results indicate that the cdc25A phosphatase is
      required to enter S phase in human cells and suggest that this enzyme is part of
      an auto-amplification loop analogous to that described at the G2/M transition. We
      discuss the nature of the in vivo substrate of the cdc25A phosphatase in S phase
      and the possible implications for the regulation of S phase entry.

PMID- 7523112
TI  - Diphtheria toxin at low pH depolarizes the membrane, increases the membrane
      conductance and induces a new type of ion channel in Vero cells.
AB  - Receptor-dependent translocation of diphtheria toxin across the surface membrane
      of Vero cells was studied using patch clamp techniques. Translocation was induced
      by exposing cells with surface-bound toxin to low pH. Whole cell current and
      voltage clamp recordings showed that toxin translocation was associated with
      membrane depolarization and increased membrane conductance. The conductance
      increase was voltage independent, with a reversal potential of approximately 15
      mV. This value was unaffected by changing the Cl- gradient across the membrane
      and microfluorometric measurements showed that the cytosolic Ca2+ concentration
      was only marginally elevated by the translocation. The conductance increase is
      thus mainly due to monovalent cations. Exposing outside-out and cell-attached
      patches with bound toxin to low pH induced a new type of ion channel in the
      membrane. The channel current was inward at negative membrane potentials and the
      single channel conductance was approximately 30 pS. This value is about three
      times larger than for receptor-independent channels induced by diphtheria toxin
      or toxin fragments in artificial lipid membranes.

PMID- 7523111
TI  - The HOG pathway controls osmotic regulation of transcription via the stress
      response element (STRE) of the Saccharomyces cerevisiae CTT1 gene.
AB  - The HOG signal pathway of the yeast Saccharomyces cerevisiae is defined by the
      PBS2 and HOG1 genes encoding members of the MAP kinase kinase and of the MAP
      kinase family, respectively. Mutations in this pathway (deletions of PBS2 or
      HOG1, or point mutations in HOG1) almost completely abolish the induction of
      transcription by osmotic stress that is mediated by stress response elements
      (STREs). We have demonstrated previously that STREs also mediate induction of
      transcription by heat shock, nitrogen starvation and oxidative stress. This study
      shows that they are also activated by low external pH, sorbate, benzoate or
      ethanol stress. Induction by these other stress signals appears to be HOG pathway
      independent. HOG1-dependent osmotic induction of transcription of the CTT1 gene
      encoding the cytosolic catalase T occurs in the presence of a protein synthesis
      inhibitor and can be detected rapidly after an increase of tyrosine
      phosphorylation of Hog1p triggered by high osmolarity. Consistent with a role of
      STREs in the induction of stress resistance, a number of other stress protein
      genes (e.g. HSP104) are regulated like CTT1. Furthermore, catalase T was shown to
      be important for viability under severe osmotic stress, and heat shock was
      demonstrated to provide cross-protection against osmotic stress.

PMID- 7523114
TI  - Self-splicing group I intron in cyanobacterial initiator methionine tRNA:
      evidence for lateral transfer of introns in bacteria.
AB  - A group I self-splicing intron has been found in the anticodon loop of tRNA(fMet)
      genes in three cyanobacterial genera: Dermocarpa, Scytonema and Synechocystis; it
      is absent in nine others. The Synechocystis intron is also interrupted by an open
      reading frame (ORF) of 150 codons. Of these three bacteria, only Scytonema also
      contains the group I intron that has previously been reported in tRNA(Leu) (UAA)
      genes in both cyanobacteria and chloroplasts. The presence of an ORF in the
      tRNA(fMet) intron, the sporadic distribution of the intron among cyanobacteria
      and the lack of correlation between relatedness of the intron sequences and the
      bacteria in which they reside, are all consistent with recent introduction of
      this intron by lateral transfer.

PMID- 7523113
TI  - Divergent signalling via APO-1/Fas and the TNF receptor, two homologous molecules
      involved in physiological cell death.
AB  - Tumor necrosis factor receptor (TNF-R) and APO-1/Fas (CD95) are members of the
      tumor necrosis factor/nerve growth factor receptor superfamily involved in
      various forms of physiological cell death. Due to the structural homology between
      these receptors and their ligands, it has been suggested that APO-1/Fas and TNF-R
      kill cells by similar mechanisms. Here, we compared the killing pathways mediated
      by each receptor molecule in TNF-sensitive L929 cells stably transfected with APO
      1/Fas cDNA. Morphological analysis revealed that TNF-induced cell death resembles
      necrosis, while APO-1/Fas-mediated cell killing shows an apoptotic pattern,
      evident by the appearance of membrane blebbing, nuclear condensation and non
      random DNA degradation. Studies with inhibitors of several intracellular pathways
      further demonstrate that the mechanisms of TNF- and APO-1/Fas-mediated cell
      killing are substantially different. TNF cytotoxicity is mediated by reactive
      oxygen intermediates generated during mitochondrial respiration. However, these
      mediators are not involved in APO-1/Fas-mediated cell death as neither
      mitochondrial inhibitors nor antioxidants exert a protecting effect. Moreover,
      several inhibitors of calcium metabolism, ADP ribosylation and phospholipase
      action suppress TNF cytotoxicity, but not APO-1/Fas-mediated apoptosis.
      Additional differences between the two molecules were observed at the
      transcriptional level. Whereas transcription factor NF-kappa B was readily
      activated by TNF, activation was not induced by triggering APO-1/Fas. These data
      suggest that the two molecules, though structurally related, utilize distinct
      signal transduction pathways, even in a single cell type. Hence, cells may
      undergo different programs of cell death depending on the activating stimulus.

PMID- 7523115
TI  - Processing of the pre-beta-amyloid protein by cathepsin D is enhanced by a
      familial Alzheimer's disease mutation.
AB  - A major pre-beta-amyloid protein695 (APP695) processing activity from Alzheimer's
      disease brain extracts was identified and found to be indistinguishable from the
      activity of cathepsin D.APP695 processing activity cleaved APP695 into a series
      of fragments that reacted on immunoblots to a monoclonal antibody (C286.8a)
      against beta-amyloid-(1-7)-peptide and cleaved N-dansyl-APP-(591-601)-amide at
      the Glu-Val and Met-Asp bonds. Fragments of 5.5 kDa and 10-12 kDa were formed
      from the cleavage of APP695 by cathepsin D at the Glu593-Val594 bond, and had the
      same N-terminus as a minor form of beta-amyloid released by cells. The Lys595-
      >Asn and Met596-->Leu substitutions found in a pedigree of familial Alzheimer's
      disease, increased the cathepsin D-catalyzed rate of accumulation of 5.5 kDa and
      10-12 kDa C286.8a-reactive fragments 5-10fold. This substitution also increased
      the rate of N-dansyl-APP-(591-601)-amide cleavage at the Xaa-Asp bond by up to 41
      fold. These observations suggest a role of cathepsin D in beta-amyloid formation
      under certain circumstances.

PMID- 7523116
TI  - Tyr394 and Tyr505 are autophosphorylated in recombinant Lck protein-tyrosine
      kinase expressed in Escherichia coli.
AB  - The activity of the Src family protein-tyrosine kinase p56lck is regulated by
      phosphorylation and dephosphorylation of two critical tyrosine residues Tyr394
      and Tyr505. Tyr394 is autophosphorylated after p56lck activation, whereas
      phosphorylation of Tyr505 is believed to be due to p50csk which negatively
      modulates p56lck activity. To determine whether Tyr505 could be
      autophosphorylated, we used the prokaryotic glutathione S-transferase expression
      system to express wild-type Lck, the mutants [Y394F]Lck and [Y505F]Lck, a kinase
      deficient p56lck with a mutation of the ATP-binding site [K273E]Lck and a double
      mutant [Y394F, Y505F]Lck. We studied the kinase activities and the patterns of
      autophosphorylation for tyrosine residues in these mutants and wild-type Lck both
      in vivo and in vitro. Wild-type Lck, [Y505F]Lck and [Y394F]Lck were
      phosphorylated on tyrosine. Both the kinase-deficient mutant[K273E]Lck and the
      double mutant [Y394F, Y505F]Lck did not react with monoclonal anti
      phosphotyrosine antibody [anti-Y(P) mAb], thus providing evidence that (a) the
      bacterial strains used lacked intrinsic protein-tyrosine kinase activities, and
      therefore tyrosine phosphorylations of wild-type Lck, [Y505F]Lck and [Y394F]Lck
      are due to autophosphorylation occurring in vivo in bacteria, and (b) that p56lck
      can only be autophosphorylated on two tyrosine residues, namely Tyr394 and
      Tyr505. Phosphopeptide mapping analysis confirmed that p56lck can undergo
      autophosphorylation on these two tyrosine residues. We propose that
      autophosphorylation at Tyr505 of p56lck may represent an accessory mechanism for
      the down-regulation of the tyrosine kinase activity of p56lck.

PMID- 7523117
TI  - A novel class of adhesion acidic glycans in sea urchin embryos. Isolation,
      characterization and immunological studies during early embryonal development.
AB  - Total glycans were isolated and purified from Lytechinus pictus embryos at early
      developmental stages by gel-filtration chromatography after pronase and DNase
      digestion, and alkali-borohydride treatment. Fractionation by Superose 6 and HPLC
      gel-filtration chromatography revealed three major glycan fractions of 580, 150
      and 2 kDa consistently throughout development up to the stage of end gastrula.
      The 580-kDa and the 150-kDa glycan fractions isolated from fertilized eggs up to
      the stage of end gastrula are highly acidic, whereas the 2-kDa glycan fractions
      have no detectable uronic acid residues and charged groups. Chemical analysis of
      the glycan fractions showed that their content of neutral hexoses, uronic acid,
      GlcNAc, GalNAc and sulphate changes during development. The resistance of the 580
      kDa and the 150-kDa glycan fractions to glycosaminoglycan-degrading enzymes
      indicates a structure which is different from the glycosaminoglycans. The
      incorporation of [3H]glucosamine into the 580-kDa, the 150-kDa and the 2-kDa
      glycan fractions showed that glycan synthesis increases in a linear fashion from
      the stage of early blastulation to end of gastrulation. Maximal incorporation of
      the radioligand occurs in the 2-kDa glycan fractions, with the highest rate
      observed between the stages of mesenchyme blastula and early gastrulation.
      Immunological studies, using a monoclonal antibody which inhibits cell
      aggregation, showed that the total glycans isolated from morula, early
      blastulation, early gastrulation and the end of gastrulation carry cell-adhesion
      epitopes. The number of these epitopes, as indicated by the intensity of the
      immunostaining, increases from morula formation to end-gastrulation stages and
      correlates with the increased rate of morphogenetic movements. These results
      suggest that controlled expression of the cell-adhesion glycan epitopes play an
      important role in sea urchin gastrulation.

PMID- 7523118
TI  - GPIIIa(90-102) and GPIIIa(631-653) epitopes as markers of conformational changes
      occurring during the activation of the glycoprotein IIb/IIIa complex.
AB  - To evaluate the range of conformational changes in the GPIIIa subunit upon the
      interaction of GPIIb/IIIa complex with fibrinogen, we employed two polyclonal
      antipeptide antibodies against synthetic peptides spanning chain segments (90
      102) and (631-653) of GPIIIa. The first peptide fragment derives from the region
      preceding the putative binding site for the RGD sequence, while the second one is
      located in the vicinity of membrane lipid bilayer. The resting platelets bound
      about 13,700 and 11,500 molecules of anti-[GPIIIa(90-102)] and anti-[GPIIIa(631
      653)] antibodies, respectively. The anti-[GPIIIa(90-102)] antibodies
      preferentially bound to the active form of GPIIb/IIIa complex. This binding was
      significantly reduced after dissociation of the complex, indicating that the
      recognized epitopes became partially hidden in the GPIIIa subunit. In contrast to
      anti-[GPIIIa(90-102)], the anti-[GPIIIa(631-653)] antibodies reacted optimally
      with the EDTA-treated GPIIb/IIIa. Upon stimulation of platelets with ADP, the
      number of binding sites anti-[GPIIIa(631-653)] was reduced 2.8-fold. The binding
      affinity of anti-[GPIIIa(90-102)] antibodies to the resting and ADP-stimulated
      platelets differed 4.7-fold, indicating that the stimulation of the platelets
      with ADP resulted in better exposure of this epitope. This binding was inhibited
      almost totally by fibrinogen in a dose-dependent fashion. Similarly, fibrinogen
      inhibited binding of the anti-[GPIIIa(631-653)] antibodies to the platelets. In
      the reversed system, binding of fibrinogen to platelets was inhibited only to 60%
      by the anti-[GPIIIa(90-102)] antibodies. Such inhibition of fibrinogen binding
      was sufficient to block aggregation of ADP-stimulated platelets by the anti
      [GPIIIa(90-102)] antibodies in platelet-rich plasma. In contrast, the anti
      [GPIIIa(631-653)] potentiated fibrinogen binding by 20%, confirming that there
      were additional interacting sites for fibrinogen in other regions of the
      GPIIb/IIIa complex. The presented data indicate that the activation of the
      fibrinogen receptor is associated with extensive conformational changes in the
      GPIIIa subunit, detectable by use of antipeptide antibodies recognizing not only
      the epitopes located next to the putative ligand-binding site but also the
      epitopes in the vicinity of the platelet membrane lipid bilayer.

PMID- 7523119
TI  - Purification and properties of a succinyltransferase from Pseudomonas aeruginosa
      specific for both arginine and ornithine.
AB  - The arginine and ornithine succinyltransferase from Pseudomonas aeruginosa, a
      bifunctional enzyme involved in the aerobic utilization of arginine and
      ornithine, has been purified to homogeneity. The apparent molecular mass of the
      native enzyme was 150 kDa by gel filtration and 140 kDa by polyacrylamide gel
      electrophoresis under non-denaturing conditions. After SDS/PAGE two subunits of
      35 kDa and 37 kDa were evident, indicating that the enzyme is a heterotetramer.
      Microsequence analysis of the electroblotted protein bands gave two different but
      well-conserved N-terminal amino acid sequences. The L-arginine saturation curve
      followed Henri-Michaelis kinetics with an apparent Km value of 0.5 mM. The
      sigmoidal saturation curve for L-ornithine indicated allosteric behaviour. D
      Arginine, a competitive inhibitor with respect to L-arginine, reduced L-ornithine
      cooperativity. In the presence of spermidine, the L-ornithine saturation curve
      became increasingly sigmoidal, the Hill coefficient shifting from 2.5 in the
      absence of the inhibitor, to 3.5 in the presence of 20 mM spermidine. The L
      arginine analog, L-homoarginine, was also a substrate of the succinyltransferase,
      and the saturation of the enzyme by this substrate was also cooperative. All
      these data confirmed the allosteric nature of the enzyme. Moreover, a mutant
      growing faster on L-ornithine than the parent strain had a modified
      succinyltransferase with a reduced L-ornithine cooperativity. The fate of L
      homoarginine was different depending on whether the succinyltransferase was
      induced or not; excreted succinylhomoarginine was found in cultures induced for
      the transferase activity whereas guanidinovalerate was excreted in non-induced
      cultures. The 'waste' of succinyl CoA, which could not be regenerated from the
      excreted succinylhomoarginine, explained the inhibition exerted by L-homoarginine
      on growth when ornithine or arginine was used as the growth medium.

PMID- 7523120
TI  - Characterization of the murine plasma fibrinolytic system.
AB  - The main components of the murine plasma fibrinolytic system, including
      fibrinogen, plasminogen, alpha 2-antiplasmin, tissue-type plasminogen activator
      and plasminogen activator inhibitor-1, were purified to homogeneity and their
      interactions were quantitated and compared with those of the human counterparts.
      Initial activation rates of murine and human plasminogen by autologous tissue
      type plasminogen activator were comparable (catalytic efficiencies, k2/Km, of 0.4
      and 0.6 mM-1 s-1, respectively), but murine plasminogen appeared to be resistant
      to activation by human tissue-type plasminogen activator (k2/Km = 0.01 mM-1 s-1).
      Plasminogen activation by tissue-type plasminogen activator was stimulated 100-
      and 160-fold in autologous murine and human systems, respectively, with
      saturating concentrations of 0.45 and 0.32 microM, respectively, of CNBr-digested
      fibrinogen. Nearly quantitative binding (85-90%) of tissue-type plasminogen
      activator to fibrin was observed both in autologous and heterologous systems.
      Murine and human plasmin were very rapidly inhibited by autologous and
      heterologous alpha 2-antiplasmin (second-order inhibition rate constants, k1,app,
      of 2.1-2.3 x 10(7) M-1 s-1) and murine and human tissue-type plasminogen
      activator were very rapidly inhibited by autologous or heterologous plasminogen
      activator inhibitor-1 (k1,app of 1.8-4.9 x 10(7) M-1 s-1). Two-chain murine
      tissue-type plasminogen activator (added at a concentration of 1 microgram/ml)
      was inhibited in normal or plasminogen activator inhibitor-1-deficient murine
      plasma with half-lives of 6.5 min and 4.2 min, respectively, as compared to 80
      min for human tissue-type plasminogen activator, suggesting that murine plasma
      contains proteinase inhibitors other than plasminogen activator inhibitor-1 which
      efficiently inhibit autologous tissue-type plasminogen activator. Clot lysis
      experiments in autologous plasma revealed that the murine plasma fibrinolytic
      system is more resistant to activation than the human system (20-30% clot lysis
      in 2 h with 100 nM tissue-type plasminogen activator in the murine system, as
      compared to 50% clot lysis in 2 h with 3.5 nM tissue-type plasminogen activator
      in the human system). Several mechanisms appear to be involved in this relative
      resistance observed in the murine system, including resistance of murine
      plasminogen to quantitative activation and short plasma half-life of murine
      tissue-type plasminogen activator. Thus, although these quantitative interactions
      between purified components of the murine fibrinolytic system appear to be
      comparable to those between the human counterparts, murine plasma clots are > 30
      fold more resistant to lysis with autologous tissue-type plasminogen activator
      than human plasma clots.

PMID- 7523121
TI  - High-level expression of the human neurokinin-1 receptor in mammalian cell lines
      using the Semliki Forest virus expression system.
AB  - Human neurokinin-1 receptor cDNA was introduced into the pSFV1 Semliki Forest
      virus (SFV) vector and the in vitro transcribed RNA was electroporated into BHK
      cells with pSFV-Helper RNA. This procedure resulted in the packaging of a high
      titer SFV-NK-1 virus stock containing approximately 5 x 10(9) infective units/ml.
      Infection of baby hamster kidney, COS-7, Chinese hamster ovary and human
      osteosarcoma cells yielded high levels of human neurokinin-1 receptor expression
      as assessed by [3H]substance P binding. The maximal receptor expression level
      obtained was 4 x 10(6) receptors/cell and studies of the post-infection time
      indicated that a high level of receptor expression was observed 10-24 h post
      infection. The human neurokinin-1 receptor expressed in infected baby hamster
      kidney, COS-7 and Chinese hamster ovary cells was able to stimulate Ca2+
      mobilization indicating functional coupling to guanine-nucleotide-binding
      proteins. The application of the Semliki Forest virus expression system will
      permit the rapid and efficient production of large quantities of receptor protein
      for both pharmacological and structural studies.

PMID- 7523122
TI  - A unique autophosphorylation site in the platelet-derived growth factor alpha
      receptor from a heterodimeric receptor complex.
AB  - The platelet-derived growth factor (PDGF) alpha and beta receptors undergo
      dimerization as a consequence of ligand binding. Depending on the PDGF isoform
      (PDGF-AA, -AB or -BB), homodimers or heterodimers of receptors are formed. In
      this study, we have used transfected porcine aortic endothelial cells,
      coexpressing cDNAs for the alpha receptor and the beta receptor at comparable
      levels, to investigate the properties of the alpha beta-heterodimeric receptor
      complex. PDGF-AB, which mainly induced alpha beta-heterodimeric complexes, was
      the most efficient isoform for stimulating mitogenicity. Actin reorganization, in
      the form of circular membrane ruffling and chemotaxis, was induced by PDGF-AB and
      PDGF-BB, but not by PDGF-AA, thus indicating that the beta receptor in the
      homodimeric or heterodimeric configuration was required for induction of motility
      responses. The molecular basis for the apparent receptor dimer-specific
      properties was examined by analyzing receptor autophosphorylation and
      phosphorylation of substrates. The alpha receptor was found to be phosphorylated
      at an additional tyrosine residue, Tyr754, in the heterodimeric complex as
      compared to the alpha alpha receptor homodimer. Phosphorylation of this tyrosine
      residue could permit the binding of a specific signal-tranducing protein. A
      candidate is a 134,000-M(r) protein, which was shown to associate preferentially
      with the alpha receptor in the heterodimeric receptor complex. It is possible
      that phosphorylated Tyr754 in the alpha receptor mediates activation of specific
      signal-tranducing molecules like the 134,000-M(r) substrate, and thereby
      initiates signal-tranduction pathways from the alpha beta receptor heterodimer,
      which are distinct from those initiated via homodimeric receptor complexes.

PMID- 7523124
TI  - Activation of the silent human cytokeratin 17 pseudogene-promoter region by
      cryptic enhancer elements of the cytokeratin 17 gene.
AB  - We have previously described the three loci CK-CA, CK-CB and CK-CC in the human
      genome that contain clustered type-I cytokeratin genes and reported the complete
      nucleic acid sequences of the functional cytokeratin 17 gene located in CK-CA and
      two closely related pseudogenes present in CK-CB and CK-CC [Troyanovsky, S.M.,
      Leube, R.E. & Franke, W.W. (1992) Eur. J. Cell Biol. 59, 127-137]. By nucleic
      acid sequence analysis, we now show that extensive similarities between the
      functional gene and the pseudogenes exist in the 5'-upstream region. However,
      despite the high degree of nucleic acid identity (94%), only the 5'-upstream
      region of the functional gene was able to induce significant transcriptional
      activity in transfected cells of epithelial origin. Using chimeric upstream
      regions consisting of different fragments from the pseudogene and the functional
      gene, we made the surprising observation that cis elements in the proximal 5'
      upstream region of the pseudogene promoter can cooperate with distal enhancer
      elements of the functional gene to induce strong chloramphenicol-O
      acetyltransferase activity in transfected HeLa cells. A major site in the
      proximal upstream region was identified by deoxyribonuclease protection
      experiments to be necessary for this cooperative effect. The structure and
      properties of this element were further analysed by transfection of different
      chloramphenicol-O-acetyltransferase gene constructs, and by nucleic acid sequence
      comparison to corresponding regions of the related cytokeratins 14 and 16. It is
      concluded that the upstream regions identified in this study contribute to the
      strong expression of the human cytokeratin 17 gene in a coordinated fashion.

PMID- 7523123
TI  - Heterotropic modulation of the protease-inhibitor-recognition process. Cations
      effect the binding properties of alpha-chymotrypsin.
AB  - The effect of calcium and lanthanide ions (e.g. terbium) on the binding
      properties of alpha-chymotrypsin has been studied focussing on the modulation
      exerted by cations on the interaction of the enzyme with the bovine pancreatic
      trypsin inhibitor (BPTI or Kunitz inhibitor). The results obtained indicate that
      the cation binding induces conformational transitions, on the enzyme molecule,
      which destabilize the enzyme-inhibitor complex formation affecting the
      interaction of the inhibitor with the secondary specificity site of the
      proteolytic enzyme. This negative heterotropic effect can be observed only with
      macromolecular inhibitors (or substrates), displaying an extended interacting
      surface with the enzyme, and it seems linked to the number of positive charges
      carried by the cations. Thus, owing to the large conformational changes induced
      by the binding of trivalent cations, the divalent ones (e.g. calcium) appear to
      be more suitable for a fine regulation of the enzyme activity. The mutual
      correlation between inhibitors binding to (and calcium release by) the
      proteolytic enzymes (and vice versa) could assume an important physiological
      significance linking parameters, such as calcium concentration and the activity
      levels of proteolytic enzymes, which are both of great importance for the cell
      life.

PMID- 7523125
TI  - Differential location of nucleic acids within interchromatin granule clusters.
AB  - We have examined in great detail the distribution of nucleic acids within
      interchromatin granule clusters in different cell types by means of various
      immunocytochemical approaches. Using the in situ polyadenylate nucleotidyl
      transferase-immunogold technique for RNA detection or anti-RNA antibodies, we
      decisively demonstrate the presence of appreciable amount of RNA in clusters of
      interchromatin granules of untreated cells. Neither the in situ terminal
      deoxynucleotidyl transferase-immunogold technique nor anti-DNA antibodies, nor
      the in situ nick-translation technique for DNA detection have revealed any DNA in
      the interchromatin granule clusters. However, dispersed chromatin sensitive to
      DNase I are found at the borders and in the close vicinity of interchromatin
      granule clusters. The results indicate that interchromatin granule clusters
      should not be nuclear structures directly involved in RNA transcription but
      rather in some other steps of RNA metabolism.

PMID- 7523126
TI  - Intracisternal crystals in pancreatic acinar cells: failure in the distinct
      aggregation of secretory proteins.
AB  - Mechanisms leading to the formation of crystalline inclusions in the cisternal
      space of the rough endoplasmic reticulum are poorly understood. This phenomenon
      was investigated in pancreatic acinar cells using two different experimental
      models: 1) Intraperitoneal injection of DL-p-chlorophenylalanine methyl ester,
      and 2) culture of isolated acinar cells within the Matrigel basement membrane in
      the presence of 2% dimethyl sulfoxide. Features and composition of induced
      crystals were analyzed by protein A-gold and lectin-gold cytochemistry, electron
      microscope autoradiography, electron energy loss spectroscopic imaging and energy
      dispersive X-ray analysis. Crystal formation occurred in ribosome partially free
      rough endoplasmic reticulum (RER) regions and was similar in both experimental
      protocols. The protein A-gold revealed the presence of nine major pancreatic
      enzymes in the crystals. However, the labeling intensities varied among enzymes
      with higher concentrations of amylase than chymotrypsinogen when compared to the
      secretory granules. Concanavalin A and Helix pomatia labelings were weak over the
      crystals and did not correspond to those of RER or secretory granules. Sulfur
      contents in crystals were lower than phosphorus and their ratio was opposite to
      the one found in secretory granules. Electron microscope autoradiography
      demonstrated incorporation of radiolabeled leucine and presence of newly
      synthesized proteins in the crystals. Furthermore, cells containing both crystals
      and secretory granules displayed silver grains in most of the cellular
      compartments involved in secretion. Thus, failure in the normal concentration and
      sorting process of secretory proteins leading to crystal formation includes
      changes in protein glycosylation and decrease of disulfide bond formation while
      retaining secretory capabilities.

PMID- 7523127
TI  - C-kit ligand induction of immature neutrophils in cultures of human umbilical
      cord blood.
AB  - Human cord blood cells cultured in suspension with soluble c-kit ligand produce
      immature mast cells from their agranular precursors; cocultures of cord blood and
      mouse 3T3 fibroblasts produce fully mature human mast cells. We noted cells of
      the neutrophil lineage in the c-kit ligand-supplemented suspension cultures.
      Similar cultures were prepared from individual cord bloods with several sources
      of the c-kit ligand, including mouse fibroblast conditioned media, a partially
      purified mouse 3T3 fibroblast factor(s), recombinant human stem cell factor,
      recombinant murine mast cell growth factor, and were sampled sequentially for
      routine and cytochemical ultrastructural studies. These studies show that
      peroxidase-positive azurophilic granule-containing neutrophilic myelocytes
      develop in quantity from their agranular precursors in cord blood when the c-kit
      ligand is present, but little to no maturation to mature neutrophils with
      specific granules occurs. Specific granules were also absent in the neutrophil
      precursors. The effect of c-kit ligand in vitro on two cell lineages in man is
      similar--i.e., it permits the development of immature cells to differentiate from
      their agranular precursors in cord blood, but complete maturation to fully mature
      mast cells or neutrophils does not occur.

PMID- 7523128
TI  - Relationship of ultrasonographic findings to histology in prostate cancer.
AB  - We compared ultrasonic findings and histology in 25 patients with prostate
      cancer. Ultrasonically guided transperineal biopsy of focal prostatic lesions was
      performed in 19 patients, in whom prostate cancer was suspected. Six of them had
      two different echogenic areas in the same focal lesion, so a total of 25
      echogenic areas were assessed. Fourteen of these 25 areas were hypoechoic. The
      Gleason score varied, but residual prostatic glands and cancer glands with
      slightly enlarged lumen did not exist. Six of the areas were slightly more
      echogenic than the above 14 areas, and cribriform cancer with slightly enlarged
      glands occupied the greater part of these specimens. Four of the areas were
      isoechoic, and they contained residual prostatic glands showing a normal
      distribution, regardless of the Gleason score or grade of tumor infiltration. The
      only hyperechoic lesion contained numerous tiny areas of calcification. In the 6
      patients without focal lesions, the peripheral and transition zones showed a
      normal echogenicity. Two of these patients had cancer in the transition zone, and
      biopsy showed tumor glands with slightly enlarged lumens. In the 4 patients,
      various-sized tumors were seen, but there was a normal distribution of residual
      prostatic glands and stroma. These results indicated that prostatic echogenicity
      is determined by the presence of tumor glands with enlarged lumina as well as
      residual prostatic glands and stroma.

PMID- 7523130
TI  - Effects of 3 months' neoadjuvant hormonal treatment with a GnRH analogue
      (triptorelin) prior to radical retropubic prostatectomy on prostate-specific
      antigen and tumour volume in prostate cancer.
AB  - In this retrospective study the relationship between serum prostate-specific
      antigen (PSA) and tumour volume (assessed by the planimetric method on whole
      mount section) was analysed in 56 patients subjected to radical prostatectomy, of
      whom 28 received 3 months of neoadjuvant GnRH analogue (triptorelin) treatment.
      Serum PSA in the control group was strongly correlated to the tumour volume while
      no such correlation was found after hormonal pretreatment (r = 0.84 vs. 0.18),
      indicating that serum PSA is unreliable as a tumour marker after hormonal
      deprivation. When the pretreatment PSA (before hormonal deprivation) per tumour
      volume ratio was calculated, a group of 10 patients (36%) showed considerably
      higher values, suggesting true tumour volume reduction in those patients as a
      result of the neoadjuvant hormonal treatment.

PMID- 7523129
TI  - Prostate-specific antigen in urine.
AB  - We investigated concentrations of prostate-specific antigen (PSA) in mid-stream
      urine of 213 patients. Among them were 34 females. Diagnoses of the male patients
      were 42 benign prostatic hypertrophy (BPH), 21 localized prostate cancer prior to
      radical prostatectomy (RP), 15 post-RP without distant or local recurrence, 5
      post-RP with local recurrence and 82 with other urological diseases. PSA levels
      were determined by the Hybritech Tandem E method. Female urine samples were
      positive in 38% of the cases. This and the finding of PSA in urine of men after
      RP is most likely due to extraprostatic production by periurethral glands.
      Urinary PSA levels do not differ between patients with BPH, organ-confined
      prostate cancer and other diagnoses. In some cases, however, urine PSA levels can
      be elevated in men with local tumor recurrence after RP when serum levels are
      still undetectably low. This indicates that the determination of urinary PSA
      concentration might be useful in the follow-up of patients after RP.

PMID- 7523132
TI  - Transurethral microwave thermotherapy versus transurethral catheter therapy for
      benign prostatic hyperplasia.
AB  - Transurethral microwave thermotherapy (TUMT) is a single outpatient treatment for
      benign prostatic hyperplasia. It produces good symptomatic relief but minimal
      objective improvement in mean flow rates. We wished to evaluate the placebo
      effect of the transurethral catheter. We evaluated 40 patients with outflow
      obstruction, 20 had TUMT for 1 h and 20 had a catheter placed in the urethra
      without treatment for 1 h. Urinary flow rates improved in both groups (12.8-14.6
      with TUMT, 10.0-12.4 with catheter). Significant reduction from pretreatment
      values occurred in symptom scores and postvoid residual urine volume in both
      groups following treatment. The subjective results of TUMT and the placebo effect
      seen in the catheter group cast doubt on our understanding of the mechanism of
      action of TUMT.

PMID- 7523131
TI  - Reduction of serum prostate-specific antigen during endocrine or cytotoxic
      treatment of hormone-resistant cancer of the prostate. A preliminary report.
AB  - During the years 1988-1991 sequential serum prostate-specific antigen (PSA)
      determinations were performed during systemic treatment of hormone-resistant
      prostate cancer. The following drugs were used: prednisone (5 mg 4 times per os
      daily, 8 patients); flutamide (250 mg 3 times per os daily, 13 patients);
      estramustine phosphate (280 mg 2-3 times per os daily, 12 patients), and
      epirubicin (100 mg/m2 i.v. every 3rd week, 18 patients). In 3, 3, 4 and 6
      patients, respectively, a PSA reduction of > or = 50% was observed during
      treatment, which in 12 patients was combined with pain relief and improvement in
      the performance status. Though the exact mechanism of PSA reduction and its
      clinical significance are not completely understood, the findings suggest that
      hormone-resistant prostate cancer still contains hormone-sensitive tumor cells.
      The 4 drugs used in this study seem to be equally effective in achieving a PSA
      reduction of > or = 50%.

PMID- 7523133
TI  - Healthy monozygous twins do not recognize identical T cell epitopes on the myelin
      basic protein autoantigen.
AB  - The T cell response against myelin basic protein (MBP) has been extensively
      studied in humans because of its putative role in the pathophysiology of multiple
      sclerosis (MS). Higher concordance rates in monozygous twins as well as an
      increased risk in relatives suggest the role of genetic factors in MS
      susceptibility. Very little is known about the shaping of T cell repertoire
      towards self antigens in humans and their contribution to disease susceptibility
      in autoimmune disorders. Here we report the comparative T cell epitope
      recognition patterns towards the MBP auto-antigen in healthy identical twins. We
      have established MBP-specific T cell lines from eight sets of twins and
      characterized their fine epitope specificity. Intra-pair comparison showed the co
      existence of shared as well as distinct epitopes in six of eight pairs and a
      complete absence of concordant epitope recognition within two other pairs. These
      findings indicate that important differences in T cell repertoires against a self
      antigen may be observed between genetically identical healthy individuals,
      rendering difficult the interpretation of the differences which may be observed
      between identical twins discordant for an autoimmune disease.

PMID- 7523134
TI  - Certain anti-CD34 monoclonal antibodies induce homotypic adhesion of leukemic
      cell lines in a CD18-dependent and a CD18-independent way.
AB  - CD34 is a highly glycosylated type I membrane protein expressed by early
      hematopoietic progenitor cells as well as by endothelial cells and a subset of
      bone marrow stromal cells. CD34 is thought to play an important role during early
      hematopoiesis, although its function is unknown. We demonstrate that triggering
      of CD34 results in a rapid and vigorous homotypic adhesion in CD34+ cell lines,
      thereby providing evidence for a cell-cell adhesion function of CD34. The
      cellular adhesion event, induced by only two anti-CD34 mAb, (Immu-133 and QBend
      10) was dependent on metabolic energy, an intact cytoskeleton and the presence of
      divalent cations. Analysis of antibody inhibition experiments indicated that the
      aggregation process partially involved the CD18 molecule.

PMID- 7523135
TI  - B and T lymphocyte subsets enter peripheral lymph nodes and Peyer's patches
      without preference in vivo: no correlation occurs between their localization in
      different types of high endothelial venules and the expression of CD44, VLA-4,
      LFA-1, ICAM-1, CD2 or L-selectin.
AB  - Many lymphocytes enter tissues such as peripheral lymph nodes, and Peyer's
      patches through high endothelial venules (HEV). It is known that HEV differ in
      the expression of adhesion molecules as lymphocyte subsets do. Through the
      interaction of these molecules B and T lymphocyte subsets are thought to be
      preferentially directed into lymphoid organs. However, it is unclear which role
      these mechanisms play in vivo, since there are no studies demonstrating that
      blood lymphocyte subsets preferentially interact with different types of HEV in
      vivo. Therefore, in the present study the frequency of B, T, CD4+ and CD8+
      lymphocytes in the wall of the HEV of rat peripheral lymph nodes and Peyer's
      patches was analyzed by immunohistology. In addition, the expression of CD44, VLA
      4, LFA-1, ICAM-1, CD2 and L-selectin on B and T lymphocyte subsets of the blood
      was determined by flow cytometry. Although B and T lymphocytes showed
      significantly different levels of expression for each adhesion molecule
      investigated, the relation of B and T lymphocytes within the HEV of peripheral
      lymph nodes and Peyer's patches was strikingly comparable (38.0 +/- 5.2% vs. 40.6
      +/- 5.7% and 62.0 +/- 5.2% vs. 59.4 +/- 5.7%, respectively). The same was true
      for CD4+ and CD8+ cells. Thus, although HEV and the blood lymphocyte subsets
      differ markedly in their expression pattern of adhesion molecules, the existing
      levels are sufficient to mediate comparable entrance of B and T lymphocyte
      subsets into both types of HEV.

PMID- 7523136
TI  - Inhibition of nitric oxide synthesis by interleukin-4 may involve inhibiting the
      activation of protein kinase C epsilon.
AB  - The murine macrophage cell line, J774, when activated with interferon-gamma (IFN
      gamma), expressed high level of inducible nitric oxide synthase (iNOS) and bound
      significantly more [3H]-phorbol-dibutyrate (PBu2) compared to non-activated
      cells. The increased PBu2 binding to the particulate fraction of the cells is a
      measure of activation and translocation of protein kinase C (PKC). Both the
      expression of iNOS and the enhanced. PBU2 binding in the activated J774 cells
      were significantly inhibited by the pretreatment of the cells with murine
      recombinant interleukin-4 (IL-4). Stimulation of J774 cells by IFN-gamma and
      lipopolysaccharide results in the translocation predominantly of the epsilon
      isoform of PKC (PKC-epsilon), and this is inhibited by IL-4. The inhibition of
      PKC activation was also evident by measuring the PKC activity in the cytosolic
      fraction of the IL-4-treated cells. Activated J774 cells pretreated with IL-4 or
      a PKC-specific inhibitor (RO31-8220) failed to express mRNA of iNOS analyzed by
      PCR. These results, therefore, suggest that the inhibition of nitric oxide
      synthesis in activated murine macrophages by IL-4 is at the transcriptional level
      and may involve the inhibition of the activation of PKC-epsilon.

PMID- 7523139
TI  - Induction of HIV-1 envelope (gp120)-specific cytotoxic T lymphocyte responses in
      mice by recombinant CHO cell-derived gp120 is enhanced by enzymatic removal of N
      linked glycans.
AB  - Priming of CD8+ cytotoxic T lymphocyte (CTL) responses with recombinant proteins
      has been facilitated by the development of novel adjuvants that deliver antigens
      into the class I major histocompatibility complex (MHC) pathway. However, the
      extent to which secondary structure or glycosylation of these proteins prevents
      priming of class I MHC-restricted CTL responses is not clear. To address this
      issue, recombinant HIV-1 gp120 envelope proteins produced in yeast insect, or
      mammalian cells were compared for the ability to elicit CD8+ CTL activity in
      mice. Envelope-specific CD8+ T lymphocytes were detected in BALB/c mice immunized
      with env 2-3, a 55-kDa yeast-derived envelope protein that is not glycosylated
      and lacks a native conformation. This response was directed against a previously
      described epitope in the V3 region of gp120, as well as a newly identified
      epitope located near the carboxy-terminus of the molecule. Similar levels of V3
      directed CTL activity were observed in mice immunized with recombinant gp120
      produced in insect (Spodoptera fugiperda) cells using a baculovirus expression
      system (gp120BAC). In contrast, induction of CTL responses was considerably less
      efficient when mice were immunized with gp120CHO, a native, fully glycosylated
      envelope protein produced in mammalian CHO cells. Denaturation of gp120CHO prior
      to immunization was not sufficient to prime CTL responses. However, envelope
      specific CD8+ CTL activity was elicited when N-linked glycans were removed by
      treatment with an endoglycosidase. Possible mechanisms by which N-linked glycans
      influence delivery or processing of recombinant proteins for class I MHC
      presentation, and the implications of these findings for the design of subunit
      vaccines, are discussed.

PMID- 7523137
TI  - Identification of T cell receptor recognition residues for a viral peptide
      presented by HLA B27.
AB  - The fine specificity of T cell recognition of peptide analogues of the influenza
      nucleoprotein epitope, NP 383-391 SRYWAIRTR, was studied using HLA B27-restricted
      influenza-specific cytotoxic T cell (CTL) clones, of defined T cell receptor
      (TcR) usage, derived from unrelated individuals following natural infection. Even
      conservative amino acid substitutions of the peptide residues P4, P7 and P8
      influenced CTL recognition. These side chains are probably directly contacted by
      the TcR. CTL clones which used the TcR V alpha 14 gene segment (but not those
      using TcR V alpha 12) were also sensitive to P1 substitutions, suggesting that
      the TcR alpha chain of these clones lies over the N terminus of bound peptide,
      and that the "footprint" of certain TcR can span all exposed residues of a
      peptide bound to a major histocompatibility complex class I molecule. These
      results, taken together with previous structural and functional data, suggest
      that, for nonamer peptides bound to HLA B27, P1, P4 and P8 are "flag" residues
      with TcR-accessible side chains.

PMID- 7523138
TI  - Cross-linking CD28 leads to activation of 70-kDa S6 kinase.
AB  - Proliferation of T lymphocytes in response to antigen/MHC complexes is dependent
      upon the presence of a co-stimulatory signal; in its absence, T cells are
      rendered unresponsive to specific antigen CD28 is a T cell surface glycoprotein
      that acts as a co-stimulatory molecule when combined with signals initiated by
      the T cell receptor CD3 complex. While the biochemical signaling events following
      CD28 stimulation are still poorly defined, monoclonal antibodies (mAb) directed
      against CD28 have been shown to transduce a variety of early signals that are
      different in the presence of cross-linking antibody or the presence of phorbol 12
      myristate 13-acetate (PMA), an activator of protein kinase C (PKC). Stimulation
      of human T cells with cross-linked anti-CD28 mAb alone resulted in the activation
      of 70-kDa (p70) S6 kinase, a rapamycin-sensitive serine/threonine kinase that is
      believed to be important for cell cycle progression. Activation of p70 S6 kinase
      through CD28 was inhibited by rapamycin. Activation of p70 S6 kinase also
      increased in response to cross-linked CD3, but followed a more rapid time course
      than activation via CD2. Cyclosporin A and FK506 had no effect on p70 S6 kinase
      activity initiated via either pathway. The combination of cross-linked CD28 and
      cross-linked CD3 had no more than an additive effect on the induction of p70 S6
      kinase activity. Thus, recruitment of p70 S6 kinase activity appears to represent
      a common signal transduction event shared by both the CD28 and CD3 pathways of T
      cell activation.

PMID- 7523140
TI  - Increased Fas antigen expression in murine retrovirus-induced immunodeficiency
      syndrome, MAIDS.
AB  - The Fas antigen (Fas), which is a cell surface protein belonging to the tumor
      necrosis factor receptor family, mediates apoptosis. To assess the contribution
      of Fas to the pathogenesis of retrovirus-induced immunodeficiency, we examined
      the kinetics of Fas expression on the lymphocytes during the course of murine
      acquired immunodeficiency syndrome (MAIDS) induced by a defective LP-BM5 murine
      leukemia virus. The Fas-positive cells were increased in proportion both in alpha
      beta T cells and B cells with the progression of MAIDS. The appearance of Fas
      positive cells in alpha beta T cells preceded those in B cells during the course
      of MAIDS. Among alpha beta T cells, about half of the Thy1.2+ alpha beta T cells
      were positive for Fas, while almost all of Thy1.2- CD4+ alpha beta T cells were
      of the Fas-positive phenotype. The Fas-positive cells in MAIDS mice, especially
      unique Thy1.2-CD4+ alpha beta T cells, were easily rendered apoptotic by
      stimulation via Fas, indicating that Fas expressed on the lymphocytes is
      functional. Furthermore, concomitant infection with Mycobacterium avium in MAIDS
      mice caused a marked increase in Fas-positive cells accompanied by a severely
      impaired T cell reactivity to polyclonal stimuli. Taken together, these results
      suggest that possible participation of the Fas system in the pathogenesis of
      retrovirus-induced immunodeficiency.

PMID- 7523142
TI  - Adhesion molecules from the LFA-1/ICAM-1,3 and VLA-4/VCAM-1 pathways on T
      lymphocytes and vascular endothelium in Graves' and Hashimoto's thyroid glands.
AB  - Lymphocytic infiltration of the thyroid gland in autoimmune thyroid disorders
      requires, as a first step, their attachment to endothelial cells (EC) and
      subsequently, their interaction with thyrocytes and extracellular matrix
      proteins. A number of different ligand molecules have been identified to mediate
      the interaction between EC and leukocyte subpopulations. In this study, we
      examined by flow cytometry and immunohistochemical techniques, the expression of
      integrin receptors and their counter-receptors by infiltrating lymphocytes and
      vascular endothelium in thyroid glands from patients with Graves' disease (GD)
      and Hashimoto's thyroiditis (HT). A high proportion of GD intrathyroidal T
      lymphocytes expressed the CD69 and gp95/85 (Ea2) activation antigens as well as
      an increased number of LFA-alpha L, VLA-alpha 1, -alpha 4, -alpha 5, and beta 1
      integrin receptors, as compared with peripheral blood T lymphocytes from the same
      patients. The expression of intercellular adhesion molecule (ICAM)-1 was
      increased in EC from GD and HT thyroids. In addition, an up-regulated de novo
      expression of vascular cell adhesion molecule (VCAM)-1 was found in EC in GD and
      HT thyroids, with no reactivity in control thyroids. Dendritic cells in thyroid
      lymphoid follicles were also positive for ICAM-1 and VCAM-1. In addition, most of
      intrathyroidal mononuclear cells expressed the ICAM-3 adhesion molecule. This
      enhanced expression of ICAM-1 and VCAM-1 by thyroid EC in GD and HT may reflect
      their ability to regulate leukocyte trafficking and activation by means of the
      expression of specific ligand molecules. Our data suggest that both the LFA
      1/ICAM-1, ICAM-3 and VLA-4/VCAM-1 pathways could play a relevant role in
      localizing and perpetuating the autoimmune response in the thyroid gland in
      autoimmune thyroid disorders.

PMID- 7523143
TI  - Triggering of human natural killer cells through CD16 induces tyrosine
      phosphorylation of the p72syk kinase.
AB  - Activation of protein tyrosine kinases (PTK) is an initial and obligatory event
      for the triggering of human natural killer (NK) cells to cytotoxicity. Of the
      different PTK detected in NK cells, only p56lck has previously been shown to
      participate in NK cell activation. Here we present evidence that another PTK,
      p72syk, is involved in activation of NK cells. Stimulation with a monoclonal
      antibody to to the Fc gamma RIII receptor (CD16) induced an increased tyrosine
      phosphorylation of p72syk. This phosphorylation correlated with an increased
      tyrosine kinase activity of p72syk towards a synthetic peptide substrate. A
      severalfold increase in the catalytic activity of p72syk was also seen after
      treatment of NK cells with an inhibitor of phosphotyrosine phosphatases,
      pervanadate. We conclude that triggering of the cytotoxic response in NK cells is
      associated with activation of p72syk.

PMID- 7523141
TI  - T cell receptor-induced Fas ligand expression in cytotoxic T lymphocyte clones is
      blocked by protein tyrosine kinase inhibitors and cyclosporin A.
AB  - Fas/APO-1 is a member of the tumor necrosis factor receptor family of proteins
      that induces apoptosis when cross-linked with monoclonal antibody (mAb) or with
      its physiological ligand. Recently, both a perforin-based and a Fas-based
      mechanism have been proposed to account for T cell-mediated cytotoxicity. In the
      present study we used a murine CD8+ cytotoxic T lymphocyte (CTL) clone (KB5 C20)
      specific for H-2Kb and a T cell receptor (TcR)-negative variant of the same clone
      (2005-D4) to test (i) whether the same cell can exert both cytotoxic effector
      mechanisms and (ii) the role of TcR engagement in the induction of Fas-based
      cytotoxicity. We demonstrate that both the TcR+ and TcR- clones were able to
      express the Fas ligand after stimulation with phorbol 12-myristate 13-acetate
      (PMA)/ionomycin, and that TcR engagement of the KB5.C20 clone by means of antigen
      bearing cells or of its anticlonotypic mAb (Desire-1), which leads to Ca(2+)
      dependent, presumably perforin-based, cytotoxicity, was also able to induce Fas
      based cytotoxicity. In addition, using inhibitors we investigated the signal
      transduction pathway(s) involved in the induction of Fas-based cytotoxicity and
      expression of the Fas ligand mRNA in the CTL clones. The involvement of src-like
      protein tyrosine kinases (PTK) in Fas ligand induction through TcR engagement,
      was strongly suggested by inhibition with the src-like PTK inhibitor herbimycin
      A. Inhibition of Fas ligand induction by genistein, a more general TPK inhibitor,
      even upon stimulation by PMA plus ionomycin, suggested the possible involvement
      of PTK activities downstream of protein kinase C (PKC) in Fas ligand induction in
      CTL. Finally, the implication of the Ca2+/calmodulin-dependent protein
      phosphatase calcineurin in Fas ligand induction was demonstrated by the partial
      inhibition of Fas ligand induction with cyclosporin A. Thus, in CTL clones, Fas
      ligand expression is inducible by TcR engagement through a pathway similar to
      that involved in expression of some lymphokine genes.

PMID- 7523144
TI  - Dichotomy between the T and the B cell epitopes of the synthetic polypeptide
      (T,G)-A--L.
AB  - Studies with the well-characterized, synthetic, random-multichain polypeptide
      poly(LTyr,LGlu)-poly(DLAla)-poly(LLys) (T,G)-A-L) led to the discovery of
      determinant-specific genetic control of the immune response, as well as to other
      immunological phenomena. Moreover, the tetrapeptide TyrTyrGluGlu built on the
      same backbone ("(T-T-G-G)-A--L") was found to represent its major B cell epitope.
      We have recently shown that for interaction with major histocompatibility complex
      class II molecules and stimulation of T cells, (T,G)-A--L requires proteolytic
      processing and the resulting T cell epitopes are close to the N termini of the
      branched polymer's side chains. Thus, we were interested to elucidate the major T
      cell epitope of (T,G)-A--L, by using the ordered polypeptides (T-T-G-G)-A--L and
      (T-G-T-G)-A--L, in which only the two internal amino acids of the tetrapeptide
      attached to the side chains are switched. We established T cell lines to these
      antigens, and found that the ordered analog (T-T-G-G-)-A--L, which was defined as
      the B cell epitope of (T,G)-A--L, did not represent its T cell epitope, whereas
      (T-G-T-G)-A--L, to which only a minor anti-(T,G)-A--L Ab response was directed,
      was found to be its major T cell epitope. In addition, there was no cross
      reaction between (T-G-T-G)-A--L and (T-T-G-G)-A--L at the T cell level, similar
      to the lack of cross-reaction of their antibodies. Analysis of the repertoire of
      the T cell receptors used by these lines revealed that the (T,G)-A--L and the (T
      T-G-G)-A--L specific T cell lines were not restricted in their V alpha and V beta
      TCR usage, whereas the (T-G-T-G)-A--L-specific line was restricted by both V
      alpha and V beta T cell receptor gene products. This difference might be due to
      the thymus-independent characteristics previously described for the latter
      antigen.

PMID- 7523147
TI  - Segregation of APO-1/Fas antigen- and tumor necrosis factor receptor-mediated
      apoptosis.
AB  - The cytokine tumor necrosis factor (TNF) and the APO-1/Fas ligand represent
      typical inducers of apoptosis, i.e. programmed cell death. A limited sequence
      homology between the TNF receptor TR60 (p55) and the APO-1/Fas (CD95) antigen in
      their intracellular domains suggests overlapping signaling pathways. The TNF
      sensitive cell line KYM-1, which expresses high numbers of both TNF receptors and
      the APO-1/Fas antigen, is highly sensitive towards triggering of apoptosis by
      each of the TNF receptors, but resistant to APO-1/Fas stimulation. The opposite
      response pattern was obtained using the B lymphoid line SKW 6.4, which also co
      expresses all three cell surface molecules. Furthermore, no co-modulation of APO
      1/Fas by down-regulation of cell surface expressed TR60 and/or TR80 receptors,
      and vice versa, was found. These data argue against a physical interaction of TNF
      receptors with APO-1/Fas and, in addition, demonstrate cell specific control of
      induction of apoptosis and usage of distinct signaling pathways by these receptor
      molecules.

PMID- 7523146
TI  - Structure of HLA-B27-specific T cell epitopes. Antigen presentation in B*2703 is
      limited mostly to a subset of the antigenic determinants on B*2705.
AB  - The structure of HLA-B27-specific epitopes recognized by anti-B*2705 and anti
      B*2703 cytotoxic T lymphocytes (CTL) from three unrelated donors was examined
      with site-specific mutants at various side-chain pockets in the antigen-binding
      site. The effect of any given mutation on allorecognition correlated strongly
      with its predictable effect on peptide binding. Acidic charges in the C/F pocket
      of HLA-B27, which binds C-terminal peptide residues, strongly modulated
      allorecognition. Anti-B*2705 CTL from different donors were differently affected
      by some mutations, indicating individual differences in the structure of epitopes
      recognized by alloreactive CTL from each donor. Most anti-B*2703 CTL recognized a
      subset of epitopes that were also present on B*2705, but differed from the bulk
      of allospecific epitopes on this subtype in their smaller dependence on pocket A
      structure, where the difference between these subtypes is located, and in their
      greater dependence on Glu45, in the B pocket. The structure of the very few
      epitopes on B*2703 not shared by B*2705 was quite different from that of the much
      more predominant cross-reactive epitopes. The results strongly suggest that
      B*2703 is antigenically defective as compared with B*2705 and that this is due to
      the fact that the repertoire of peptides presented by B*2703 consists mainly of a
      subset of the B*2705-bound peptides which do not critically require the canonic
      binding of the peptidic N-terminus to a B*2705-like A pocket, because they are
      sufficiently stabilized by other contacts through the peptide binding site.

PMID- 7523148
TI  - Leukotrienes C4 and D4 promote angiogenesis via a receptor-mediated interaction.
AB  - The involvement of leukotrienes in angiogenesis was investigated in the in vivo
      chick chorioallantoic membrane system. In this system leukotrienes C4 and D4
      promoted angiogenesis in a dose-dependent manner. Leukotriene B4 was ineffective.
      The potent and selective peptidyl leukotriene receptor antagonist, SK&F 104353
      Z2, abolished the angiogenic effects of leukotrienes C4 and D4 and reduced
      unstimulated angiogenesis. These results indicate that leukotrienes C4 and D4
      promote angiogenesis in the chick chorioallantoic membrane via a receptor
      mediated interaction.

PMID- 7523145
TI  - The human natural killer cell receptor for major histocompatibility complex class
      I molecules. Surface modulation of p58 molecules and their linkage to CD3 zeta
      chain, Fc epsilon RI gamma chain and the p56lck kinase.
AB  - The natural killer cell (NK)-specific p58 surface molecules, recognized by the
      GL183 and EB6 monoclonal antibodies (mAb), have been shown to represent the
      putative NK receptor for HLA-C molecules. The interaction between p58 receptors
      and HLA-C results in inhibition of the NK-mediated target cell lysis. In this
      study, GL183-EB6+ clones (Cw4-specific), after mAb-induced surface modulation of
      EB6 molecules, acquired the ability to lyse the Cw4+ C1R cells. In NK clones co
      expressing both GL183 and EB6 molecules and unable to kill Cw3-protected target
      cells, the mAb-induced modulation of EB6 molecules resulted both in selective co
      modulation of GL183 molecules and in the lysis of Cw3-transfected P815 murine
      cells. In line with the co-modulation experiments we also show that the GL183 and
      EB6 molecules can be co-immunoprecipitated from GL183+/EB6+ clones after cell
      lysis in the presence of digitonin. The p58 receptor also revealed an association
      with molecules belonging to the zeta family (i.e. CD3 zeta and Fc epsilon RI
      gamma chains). Two-dimensional diagonal gel analysis of the p58 complex
      immunoprecipitated from polyclonally activated p58+ NK cells indicated a
      preferential association with CD3 zeta chains either in the form of covalently
      linked zeta-zeta homodimers or in the form of zeta-gamma heterodimers, while
      gamma-gamma homodimers were detectable in low amounts. However, p58+ clones
      displaying a unique association with gamma-gamma homodimers could also be
      isolated. Probing the immunoprecipitated p58 complex with anti-p56lck antibody
      also revealed an association with this member of the src family. In addition, mAb
      mediated signaling of NK clones via p58 molecules induced increments of
      p58/p56lck association. However, under the same experimental conditions that
      induced optimal in vivo tyrosine phosphorylation of the CD16-associated CD3 zeta
      chains, no tyrosine phosphorylation was detected in the p58-associated CD3 zeta
      chains. In these in vivo experiments neither anti-CD16 nor anti-p58 mAb could
      induce tyrosine phosphorylation of the gamma chains. Finally, the anti-p58
      mediated inhibition of the NK cell triggering via CD16 molecules was not
      accompanied by a down-regulation of the tyrosine phosphorylation of the CD16
      associated CD3 zeta chains.

PMID- 7523149
TI  - Neuropeptide Y and truncated neuropeptide Y analogs evoke histamine release from
      rat peritoneal mast cells. A direct effect on G proteins?
AB  - Several regulatory peptides, including neuropeptide Y, can release histamine from
      mast cells. In the present study we investigated which parts of the neuropeptide
      Y molecule are required to evoke the release of histamine from isolated rat
      peritoneal mast cells. In addition, we examined whether the histamine release
      evoked by neuropeptide Y (and by compound 48/80) is sensitive to the G protein
      inhibitors pertussis toxin and benzalkonium chloride. Neuropeptide Y released
      histamine in a concentration-dependent manner. Also a neuropeptide Y analog with
      the center part substituted by 8-aminooctanoic acid, [Aoc2-27]neuropeptide Y, and
      the cyclic form of the C-terminal hexapeptide, cyclic neuropeptide Y-(31-36),
      released histamine. The three peptides were equally effective and equally potent.
      Neuropeptide Y-(1-24)NH2 also released histamine, but its efficacy was low. The
      rank order of potency of the analogs tested did not agree with that of any of the
      previously known or postulated neuropeptide Y receptors. Pretreatment of mast
      cells with pertussis toxin or benzalkonium chloride markedly inhibited the
      histamine release evoked by neuropeptide Y, [Aoc2-27]neuropeptide Y and compound
      48/80. In conclusion, most of the histamine-releasing activity of neuropeptide Y
      resides in the six C-terminal amino acid residues. The release appears to be G
      protein-dependent and is probably not receptor mediated.

PMID- 7523150
TI  - Physiological and pharmacological characterization of the spinal tachykinin NK2
      receptor.
AB  - The goal of these investigations was to study the role of tachykinin NK2
      receptors in neonatal spinal cords using the selective NK2 receptor agonist [beta
      Ala8]neurokinin A-(4-10) and the new NK2 receptor antagonist GR 94800.
      Experiments were performed with superfused hemisected rat and gerbil spinal
      cords. Dorsal roots were electrically stimulated and the synaptically elicited
      responses and the DC-potentials were recorded extracellularly from the
      corresponding ventral roots. [beta-Ala8]neurokinin A-(4-10) depolarized ventral
      roots (0.01-10 microM) and increased their spontaneous activity in a
      concentration-dependent manner. These effects of [beta-Ala8]neurokinin A-(4-10)
      were reduced by GR 94800. The action of GR 94800 was selective because the
      depolarizing effects of similar magnitude evoked by the NK1 receptor agonist
      [Sar9,Met(O2)11]substance P were not affected by GR 94800. The pA2 values of GR
      94800 amounted to 6.0 +/- 0.4 in the rat and 5.4 +/- 0.3 in the gerbil. The NK2
      receptor agonist was more potent in the rat than in the gerbil. The estimated
      EC50 (mean +/- S.E.M.) was found to be 3.9 + 6.0/-1.3 microM in the rat and 2.4 +
      2.9/-1.3 microM in the gerbil spinal cord. The NK2 receptor agonist [beta
      Ala8]neurokinin A-(4-10) potentiated the monosynaptic reflex evoked by dorsal
      root stimulation. The potentiation manifested itself as an increase in the
      amplitude of the early component of the response. The receptor type mediating
      this effect could not be elucidated. The potentiation ranged between 30 +/- 27
      and 110 +/- 36% (0.3 and 10 microM), respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7523151
TI  - Inhibitory effect of imipramine on depolarization-induced increases in
      intracellular Ca2+ of rat cortical neurons.
AB  - We examined the effects of imipramine on the increase in intracellular Ca2+
      concentration ([Ca2+]i) induced by elevated K+ in cultured neurons of rat cortex.
      Imipramine (100 nM-200 microM) produced a concentration-dependent inhibition of
      [Ca2+]i increases induced by 25 mM K+ with an IC50 value of 32 microM. Imipramine
      had no effect on resting [Ca2+]i levels. When the cells were incubated with
      imipramine in the presence of a voltage-sensitive Ca2+ channel (VSCC) blocker,
      either nicardipine (10 microM), verapamil (10 microM), or omega-conotoxin GVIA (1
      microM), the combinations of imipramine and each blocker resulted in an additive
      inhibition of 25 mM K(+)-induced [Ca2+]i increases. The IC50 values were 44, 29
      and 24 microM, respectively, which were similar to those found when incubating
      the cells with imipramine alone. The presence or the absence of imipramine (30
      microM) in an incubation with Bay K 8644 (100 nM), a VSCC agonist, showed similar
      potentiation of the [Ca2+]i increases induced by 15 mM K+ (66 and 52%,
      respectively). On the other hand, when the cells were incubated with imipramine
      in the presence of Ni2+ (300 microM) or La3+ (0.3 microM), inorganic Ca(2+)
      channel blockers, the IC50 values of inhibition of 25 mM K(+)-induced [Ca2+]i
      increases were much lower than with imipramine alone (3.2 and 16 microM,
      respectively). However, incubations with Ni2+ combined with nicardipine or
      verapamil resulted in an additive inhibition of 25 mM K(+)-induced [Ca2+]i
      increases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523154
TI  - Expression of N-CAM by human renal cell carcinomas correlates with growth rate
      and adhesive properties.
AB  - In the present study we provide evidence for the involvement of N-CAM in the
      spreading of human renal cell carcinomas (RCC) through the interaction with the
      subendothelial matrix. We found that in tumor cell lines derived from human RCC
      the increase of growth rate and the loss of adhesiveness to inert substrate were
      accompanied by N-CAM expression and by the appearance of specific binding to
      endothelial heparan sulfate. Indeed, the adhesion of tumor cells to human
      endothelial cells and heparan sulfate in vitro was inhibited by monoclonal
      antibodies able to bind and inactivate N-CAM and was abrogated by endothelial
      cell treatment with heparitinase. Furthermore, when the renal epithelial cell
      line COS7 was transfected with a cDNA coding for N-CAM a significant increase in
      the ability to bind both endothelium and heparan sulfate in vitro was observed.
      Of note, HS complexed with epithelial growth factor could enhance the
      proliferation of RCC-derived tumor cells; this effect was also achieved by cross
      linking of N-CAM at the surface of tumor cells, suggesting that N-CAM could
      transduce an activation signal across the cell membrane. This was also supported
      by the finding that N-CAM cross-linking induced a strong calcium mobilization
      from internal stores and opening of surface calcium channels in such tumor cells.
      N-CAM was detectable in vivo at the tumor site in the areas of active
      proliferation, as judged by the coexpression of Ki67 nuclear antigen, and heparan
      sulfate was present in the wall of blood vessels in the proximity of the tumor.
      These findings would suggest that growing kidney tumors might use N-CAM to bind
      the subendothelial matrix and complexed growth factors during tissue invasion and
      spreading.

PMID- 7523152
TI  - Identification of Ag-NOR proteins, markers of proliferation related to ribosomal
      gene activity.
AB  - During mitosis, ribosomal genes are associated with a set of silver-stained
      nucleolar proteins designated Ag-nucleolar organizer region (NOR) proteins. The
      amount of Ag-NOR protein, estimated during interphase, may be used as marker of
      cell proliferation with a prognostic value for several human cancers. Our
      objective was to identify the Ag-NOR proteins in human transformed cell lines at
      specific phases of the cell cycle and in a hamster cell line that serves as model
      for active ribosomal transcription. During interphase, the major Ag-NOR proteins
      in both human and hamster cells were nucleolin and protein B23 and also proteins
      of 42, 40, and 29 kDa, which accounted for a small amount of the silver stain.
      The pIs of these proteins were between 4.5 and 5.6. During mitosis, the Ag-NOR
      proteins were either solubilized in the cytoplasm, distributed around the
      chromosomes, or associated with the ribosomal genes, i.e., in the NORs. The major
      Ag-NOR proteins associated with the ribosomal genes were the largest RNA
      polymerase I subunit, the 135-kDa NOR protein, the UBF transcription factor, and
      a 50-kDa protein. Less than 5% of the total nucleolin remained associated with
      ribosomal genes during mitosis. Using the purified RNA polymerase I complex from
      yeast, we demonstrate that the 190-, 43-, and 34.5-kDa subunits are Ag-NOR
      proteins in this species. This study demonstrates that the major Ag-NOR proteins
      in nucleoli during interphase are not the same as those associated with the
      ribosomal genes during mitosis. We conclude that the prognostic test for human
      cancer cell proliferation is largely based on the amount of the nucleolar
      proteins, nucleolin, and protein B23, which are not directly involved in
      ribosomal gene transcription. In contrast, the evaluation of active NORs in
      karyotypes during mitosis is based on the presence of some proteins of the
      ribosomal gene transcription machinery.

PMID- 7523155
TI  - Basement membrane assembly and differentiation of cultured corneal cells:
      importance of culture environment and endothelial cell interaction.
AB  - A three-dimensional corneal tissue construct was used to examine the effect of
      culture environment and endothelial cell interaction on epithelial
      differentiation and basement membrane assembly. Rabbit corneal epithelial cells
      were cultured over rabbit stromal fibroblasts in a collagen matrix with or
      without an underlying layer of immortalized mouse corneal endothelial cells
      (Muragaki, Shiota, Inoue, Ooshima, Olsen, and Ninomiya. (1992) Eur. J. Biochem.
      207, 895-902). The cultures were grown submerged or at a dry or moist interface.
      Basement membrane, anchoring fibril, and hemidesmosome assembly was monitored
      using transmission electron microscopy as well as indirect immunofluorescence
      microscopy of laminin, type VII collagen, and alpha 6 integrin. Antibodies
      against keratin 3 (K3) and alpha-enolase marked differentiated and
      undifferentiated corneal epithelial cells, respectively. When all three cell
      types were cultured at a moist interface, hemidesmosomes, anchoring fibrils, and
      a continuous basement membrane were observed 2 wk after lifting the cultures to
      an air-liquid interface (air-lift). The distribution of alpha-enolase and K3 was
      identical to patterns seen in the limbal region of the cornea. Air-lifted tissue
      constructs lacking the endothelial cell layer showed only limited distribution of
      laminin and type VII collagen at the epithelial-matrix junction. alpha 6 Integrin
      was present along the entire plasma membrane of the basal cells; epithelial
      differentiation was not complete as alpha-enolase was seen in basal and two to
      three layers of suprabasal cells. Submerged cultures without endothelial cells
      did not express differentiation markers or basement membrane components. These
      data indicate that endothelial cell interaction dramatically enhances the amount
      and quality of epithelial basement membrane assembly and that epithelial
      differentiation is influenced by the type of interface between tissue, liquid,
      and air.

PMID- 7523153
TI  - Contribution of known mitogenic signaling pathways to induction of DNA synthesis
      in quiescent Chinese hamster fibroblasts.
AB  - The mitogenic pathways so far identified in mammalian cells fall into three main
      categories: tyrosine kinase, kinase C, and the cAMP-dependent pathways. In
      quiescent murine 3T3 fibroblasts, all three signaling pathways synergize with
      each other to restart DNA synthesis. In order to establish if the same was true
      in other rodent fibroblast lines we studied the effects of factors, known to
      modulate the above-mentioned pathways, on DNA synthesis in Chinese hamster embryo
      fibroblasts (CHEF/18). The factors examined were: (1) EGF and insulin
      representative of tyrosine kinase-activating growth factors, (2) TPA as specific
      activator of protein kinase C, (3) cholera toxin, dibutyryl cyclic AMP, and
      theophylline as compounds increasing cAMP levels. We found that EGF alone is a
      strong mitogen in CHEF/18 cells, probably because it can modulate by itself all
      three pathways. Although cAMP acts as a growth enhancer in 3T3 cells, in CHEF/18
      where high levels of cAMP were found, increased concentrations of this second
      messenger produce strong DNA synthesis inhibition and temporal disturbance of
      ribosomal protein S6 phosphorylation. Possible interpretations of these findings
      are presented.

PMID- 7523156
TI  - Cross talk of tumor necrosis factor-alpha and epidermal growth factor in human
      microvascular endothelial cells.
AB  - Our previous studies imply that tumor necrosis factor-alpha (TNF-alpha) and
      epidermal growth factor (EGF) might share a common signal transduction pathway in
      human omental microvascular endothelial (HOME) cells. Exposure of cultured HOME
      cells to TNF-alpha for 10 min enhanced EGF receptor phosphorylation at a rate
      comparable to EGF. Apparent phosphorylation of tyrosine residues was observed in
      addition to serine/threonine of the EGF receptor by EGF, but only a slightly if
      any tyrosine phosphorylation by TNF-alpha. In vitro kinase activity of EGF
      receptor was also enhanced by TNF-alpha as well as by EGF. Furthermore,
      expression of the c-fos gene was enhanced in response to either EGF or TNF-alpha.
      Pretreatment of HOME cells with EGF for 12 h almost completely blocked the
      induction of the c-fos gene by EGF and partially blocked the c-fos induction by
      TNF-alpha. TNF-alpha-induced c-fos gene expression appeared to be partly due to
      its transactivation of EGF receptor. EGF and TNF-alpha could enhance c-fos gene
      expression when protein kinase C was down-regulated by phorbol ester myristate
      (PMA). Gel retardation assay with the NF-kappa B consensus sequence showed that
      NF-kappa B binding activity was dramatically activated by TNF-alpha, but not by
      EGF or PMA. The binding of another transcription factor, AP-1 (Jun/Fos), was
      enhanced by EGF, TNF-alpha, and PMA, whereas TNF-alpha could still activate AP-1
      after longer exposure to EGF. TNF-alpha-induced activation of c-fos gene appears
      to be mediated through pleiotropic mechanisms and partly through a common signal
      with EGF, possibly through EGF receptor in microvascular endothelial cells.

PMID- 7523158
TI  - Pseudomonas pseudomallei isolates collected over 25 years from a non-tropical
      endemic focus show clonality on the basis of ribotyping.
AB  - Between 1966 and 1991, melioidosis, a disease caused by Pseudomonas pseudomallei
      that is mostly confined to tropical regions, occurred in farm animals and a
      farmer in temperate south-west Western Australia. Using an Escherichia coli probe
      containing a ribosomal RNA operon, P. pseudomallei DNA from isolates from 8
      animals, a soil sample and the human case showed an identical ribotype on
      Southern blotting. The ribotype was different from the 3 commonest ribotypes seen
      in tropical Australia. This molecular typing supports the theory of clonal
      introduction of P. pseudomallei into a non-endemic region, with environmental
      contamination, local dissemination and persistence over 25 years. As melioidosis
      is often fatal in humans, such persistence in a temperate region is cause for
      concern.

PMID- 7523157
TI  - Hereditary deficiency of the seventh component of complement and recurrent
      meningococcal infection: investigations of an Irish family using a novel
      haemolytic screening assay for complement activity and C7 M/N allotyping.
AB  - Terminal complement component deficiency predisposes to meningococcal infection
      and is inherited in an autosomal co-dominant manner. An Irish family is
      described, in which 2 of 3 brothers had recurrent meningococcal infection. A
      novel screening assay was used to investigate for terminal complement deficiency
      and the 2 affected brothers were found to be completely deficient in the seventh
      component of complement (C7). Enzyme-linked immunosorbent assay for C7 revealed
      lower than normal levels in the remaining brother and parents. C7 M/N protein
      polymorphism allotyping, used to investigate the segregation of the C7 deficiency
      genes, showed that the apparently complement sufficient brother was heterozygous
      C7 deficient and a carrier of one of the deficiency genes. Complement screening
      should be carried out in any individual suffering recurrent meningococcal
      infection or infection with an uncommon meningococcal serogroup. Identification
      of complement deficient patients allows the implementation of strategies to
      prevent recurrent infection.

PMID- 7523159
TI  - Fluorometric measurement of light absorption by the rabbit cornea.
AB  - A bench specular microscope, modified to perform as a scanning microfluorometer,
      was used to make simple and precise measurements of the absorption of visible
      light by the isolated rabbit cornea. The tissue was scanned while identical FITC
      dextran solutions were perfused over both the surfaces, and the measured
      fluorescence levels in the solutions on the two sides were compared. The
      alteration in level corresponds to the difference between the absorption of the
      cornea and that of of an equal thickness of the solution, which was determined in
      a separate experiment. The absorption of light at 500 nm ranged from 0-8% with a
      mean of 3.3% (n = 20; S.E. = 0.52). Pigmented and non-pigmented rabbits did not
      show any clear difference in absorption. These results suggests that light
      absorption is not a major source of error in anterior segment fluorophotometry.

PMID- 7523161
TI  - Immunotherapy with autologous bone-marrow transplantation: rationale and results.

PMID- 7523160
TI  - Modulation of human fibroblast activity by selected angiogenesis inhibitors.
AB  - Tenon's fibroblast (TF) bleb encapsulation is a common cause of filtering surgery
      failure. Various pharmacologic agents have been used in an attempt to inhibit
      this response. The effects of three angiogenesis inhibitors were studied. AGM
      1470, a fumagillin analog and hydrocortisone 21-phosphate (HC21P) complexed with
      heparin or with the heparin analog beta-cyclodextrin tetradecasulfate (BCD-TDS)
      in modulating human tenon's fibroblasts in cell culture. It has been clinically
      demonstrated that well vascularized blebs are associated with a poorer prognosis.
      In addition to reducing bleb neovascularization, angiogenesis inhibitors may have
      an additional therapeutic role in decreasing fibroblast activity. Drug effects
      were assessed by studying cell growth rates by cell Coulter counting and rate of
      wound closure. TF's were grown in DMEM with 10% FBS and 1% PCN-strep with
      fungizone. Angiogenesis inhibitors were added to growth medium in varying
      concentrations: AGM-1470 alone, HC21P complexed with heparin and HC21P complexed
      with BCD-TDS. Controls were grown in control medium alone, medium with added
      ethanol, or with added BCD-TDS, heparin or HC21P. We found a dose related
      inhibition of cell growth with all of the angiogenesis inhibitor combinations,
      which was not seen in the control groups. Tenon's fibroblast proliferation was
      significantly inhibited by AGM-1470 as seen in the four higher concentrations (P
      < 0.05) with insignificant inhibition at the lowest concentration of AGM-1470 (P
      = 0.38). The heparin:HC21P and heparin:BCD-TDS combinations demonstrated
      significant inhibition at all concentrations (P < 0.05). Wound closure was
      significantly inhibited by all the added agents, except AGM-1470 and the
      controls. The rate of wound closure was significantly reduced by the highest
      concentrations of the heparin:HC21P and heparin:BCD-TDS combinations (P < 0.05),
      although it was not significantly affected by lower concentrations (P > 0.05).
      Rank order of potencies of these agents for inhibition of TF proliferation was
      AGM-1470, BCD-TDS:HC21P, heparin:HC21P, HC21P, while the rank order of potencies
      for these agents for inhibition of wound closure was HC21P, heparin:HC21P, BCD
      TDS:HC21P, AGM-1470. These selected angiogenesis inhibitors appear to have marked
      inhibitory effects on TF proliferation and migration, which may have a potential
      clinical role in modulating wound healing associated with glaucoma filtering
      surgery.

PMID- 7523162
TI  - Quantitative analysis of the degree of irreversible deformation of F cells and
      non-F cells and its relationship to cell density in sickle cell disease.
AB  - To study the effect of fetal hemoglobin (Hb F) on the formation of dense and
      irreversibly deformed cells in patients with sickle cell disease (SCD), we
      investigated the distribution of Hb F and Hb F cells (FC, cells having HbF) and
      the difference in the degree of irreversible deformation between FC and non-Hb F
      cells (NFC) in relation to their cell density. We used immunofluorescence to
      define FC and image analysis to quantify the degree of deformation. Blood samples
      from 16 patients with Hb F levels ranging from 4 to 24% were separated into less
      dense [top (T), d < 1.11 g/mL] and dense [bottom (B), d > or = 1.11 g/mL]
      fractions. We found higher percentages of Hb F and FC in top fractions,
      suggesting that FC are hydrated more than NFC. Quantitative shape analysis
      demonstrated that the irreversible deformation of FC in the top fraction [FC(T)]
      was not significantly different from that of NFC in the fraction [NFC(T)] (p =
      0.163), but rather that the irreversible deformation of FC in the bottom fraction
      [FC(B)] was much milder than for NFC(B) (p < 0.001). The order of the degree of
      irreversible deformation was NFC(B) > FC(B) > NFC(T) = FC(T). These results
      clearly demonstrated that FC are less susceptible to both irreversible
      deformation and dehydration than NFC, suggesting that in circulation, the
      sickling process plays a major role in cell dehydration. Additionally, we found
      that the ratio of NFC(B) to FC(B) decreased as a patient's Hb F increased (r =
      0.84) and that NFC(B) = FC(B) when Hb F was about 20%.

PMID- 7523163
TI  - Diffusible factors from the murine cell line M2-10B4 support human in vitro
      hematopoiesis.
AB  - Significantly more primitive human hematopoietic progenitors are maintained and
      differentiate when cultured separately from the stroma by a microporous membrane
      ("stroma-noncontact" cultures) than when cultured in direct contact with stromal
      layers ("stroma-contact" cultures). This suggests that diffusible stroma-derived
      factors may be sufficient for the in vitro induction of progenitor proliferation
      and differentiation. To further characterize stroma-derived factors that maintain
      long-term bone marrow culture initiating cells (LTBMC-IC), we compared the
      hematopoietic supportive capacity of human marrow stroma with that of the murine
      marrow stroma-derived fibroblast cell line M2-10B4 as well as two embryonic
      fibroblast cell lines, the human FHS-173-WE and the murine NIH-3T3 cell lines. We
      demonstrate that LTBMC-IC, present in human CD34+/HLA-DR- (DR- cells), are
      maintained equally well and give rise to similar numbers of committed
      progenitors, that is--colony-forming cells (CFC)--when cultured in contact with
      human marrow stroma or any cell line feeder (stroma-contact cultures). LTBMC-IC,
      cultured in marrow stroma or M2-10B4 stroma-noncontact cultures, were maintained
      significantly better and gave rise to significantly more CFC than when cultured
      in human marrow stroma or M2-10B4 contact cultures. However, LTBMC-IC maintenance
      and differentiation in FHS-173-WE or NIH-3T3 noncontact cultures was
      significantly less than in human marrow stroma or M2-10B4 noncontact cultures.
      These studies indicate that systematic comparison of diffusible growth
      stimulatory factors in conditioned media from M2-10B4 cells and FHS-173-WE may
      lead to the characterization of growth regulatory factors required for in vitro
      maintenance and differentiation of human primitive LTBMC-IC. Since diffusible
      factors from the M2-10B4 cell line can support human hematopoiesis, our
      observations may also have important implications for in vitro stem cell
      expansion protocols.

PMID- 7523164
TI  - The combined effects of interleukin-11, stem cell factor, and granulocyte colony
      stimulating factor on newborn rat hematopoiesis: significant enhancement of the
      absolute neutrophil count.
AB  - Dysregulation of neonatal myelopoiesis and thrombopoiesis predisposes the newborn
      to develop neutropenia and/or thrombocytopenia during states of increased demand.
      We have previously examined the effects of granulocyte colony-stimulating factor
      (G-CSF) alone or in combination with either stem cell factor (SCF) or interleukin
      11 (IL-11) on in vivo neonatal rat hematopoiesis. In this study, we determined
      the effect of the triple combination of IL-11, SCF, and G-CSF on newborn rat
      hematopoiesis. Newborn Sprague-Dawley rats (< or = 24 hours old) were
      administered intraperitoneal (IP) injections of 250 micrograms/kg IL-11, 100
      micrograms/kg SCF, 5 micrograms/kg G-CSF, or various combinations or phosphate
      buffered saline (PBS)/human serum albumin (HSA) x 14 d. Platelet and blood cell
      counts were obtained on days 1, 3, 6, 8, 10, and 13; on day 14 bone marrow
      neutrophil storage pool (BM NSP), neutrophil proliferative pool (NPP), colony
      forming units-granulocyte/macrophage (CFU-GM), and CFU-GM proliferative rates
      were determined. The triple combination failed to significantly increase the
      circulating hematocrit over other combinations or placebo. The circulating
      platelet counts, however, significantly increased during each of the IL-11
      treatment arms, but they were not enhanced by the addition of either SCF, G-CSF,
      or the combination. The triple combination of IL-11, SCF, and G-CSF induced the
      most significant increase in the circulating absolute neutrophil count (ANC)
      above any other combination or placebo. Circulating ANC increased 12-fold
      following the triple combination vs. PBS/HSA (day 14 ANC 16525 +/- 1340 vs. 1368
      +/- 197) (p < 0.001). The triple combination of IL-11, SCF, and G-CSF also
      induced the most significant increase in the BM/CFU-GM proliferative rate and BM
      NPP, p < 0.002 and p < 0.008, respectively. The highest increase in CFU-GM colony
      formation, however, occurred with both early lineage CSFs, that is, IL-11 plus
      SCF, and it was not further enhanced by the addition of G-CSF. These data suggest
      that the combination of two early-lineage CSFs, IL-11 plus SCF and G-CSF,
      significantly induces newborn rat myelopoiesis and that IL-11 alone significantly
      induces newborn rat thrombopoiesis. These results may be helpful in the design of
      future therapies to treat and/or prevent cytopenias in the newborn.

PMID- 7523165
TI  - Basic fibroblast growth factor increases retroviral-mediated gene transfer into
      human hematopoietic peripheral blood progenitor cells.
AB  - Retroviral vector-mediated gene transfer into human hematopoietic stem cells
      (HSC) may permit gene therapy of certain genetic diseases. Stimulation of HSC
      with hematopoietic growth factors (GF) has been shown to increase the level of
      retroviral transduction. We have studied the effect of basic fibroblast growth
      factor (bFGF), alone and in combination with other GFs, on the efficiency of
      transfer of the bacterial neomycin phosphotransferase (neoR) gene into human
      CD34(+)-enriched peripheral blood hematopoietic progenitor cells. The combination
      of bFGF, interleukin-3 (IL-3), IL-6, and stem cell factor (SCF) resulted in a
      transduction efficiency of 37 and 35% for G418-resistant colony-forming units
      granulocyte/macrophage (CFU-GM) and mixed colonies multipotent colony-forming
      units (CFU-GEMM), respectively, which was significantly higher than the
      corresponding figures obtained with IL-3, IL-6, and SCF. The optimal
      concentration of bFGF was between 20 and 200 ng/mL. bFGF alone had no effect on
      the transduction rate. These results indicated a synergism in the action of bFGF,
      IL-3, IL-6, and SCF to enhance gene transduction rates into human hematopoietic
      progenitor cells.

PMID- 7523167
TI  - Demonstration of differential effects of cytokines on mast cells derived from
      murine bone marrow and peripheral blood mononuclear cells.
AB  - Mouse bone marrow (BM) was cultured in the presence of recombinant mouse (rm)
      interleukin-3 (IL-3), rmIL-4, rmIL-5, rmIL-7, purified mouse (m) IL-9, rmIL-10,
      recombinant human (rh) macrophage-colony-stimulating factors (M-CSF), rm
      granulocyte-macrophage colony-stimulating factors (GM-CSF) rm stem cell factor
      (SCF), rh interferon-alpha (IFN-alpha), rmIFN-gamma, and mNGF to determine which
      cytokine would give rise to mast cells in murine BM cultures. From a starting
      population of 1 x 10(7) cells, 1.55 x 10(7) mast cells developed within 14 days
      in cultures supplemented by rmIL-3. No mast cells were seen at day 14 when any of
      the other cytokines were present alone, except for rmSCF, which supported the
      growth of < 0.01% of mast cells observed in IL-3-dependent BM cultures. When rmIL
      4, -5, -7, -10, mIL-9, rhM-CSF, rmGM-CSF, rmSCF, rhIFN-alpha, -gamma, or mNGF
      were added to BM cultures in the presence of rmIL-3, mast cell growth increased
      200% with the addition of rmSCF, and 10% when rmIL-4 or IL-9 was added. However,
      the addition of rhM-CSF, rmGM-CSF, rmIFN-gamma, and mNGF decreased the number of
      mast cells. Mast cell number, as determined by metachromatic stains, generally
      approximated the number of Fc epsilon RI+ cells as assessed by FACS analysis.
      Among the cytokines, only rmIL-4 and rmSCF were able to support the survival of
      mast cell progenitors in the absence of obvious mast cell proliferation,
      similarly to rmIL-3. Only rmSCF alone, or in combination with rmIL-3 or -4,
      supported the growth of mast cells from mouse peripheral blood mononuclear cells
      (PBMC) where the number of mast cell precursors was about 90 per 10(6) PBMC. With
      time, mouse BM cells cultured in rmIL-3 became more responsive to rmSCF. Taken
      together, these data demonstrate that IL-3 is a major early mast cell growth
      factor, that mast cells become more dependent on SCF with time, and that the
      effects of IL-3 and SCF are upregulated (IL-4) or downregulated (M-CSF, GM-CSF,
      IFN-gamma) by both growth factors and proinflammatory cytokines.

PMID- 7523166
TI  - Red blood cell depletion and enrichment of CD34+ hematopoietic progenitor cells
      from human umbilical cord blood using soybean agglutinin and CD34
      immunoselection.
AB  - Realization of the full potential of human umbilical cord blood (HUCB) as a
      source of transplantable hematopoietic progenitor cells (HPC) will be contingent
      on the development of a reliable method for ex vivo cell processing and stem cell
      enrichment. A first step in stem cell enrichment protocols involves depletion of
      the red blood cells (RBC) in the sample. We have compared several RBC depletion
      methods on the basis of recovery of total nucleated cells. It was found that 3%
      gelatin was effective at depleting RBC with a nucleated cell recovery of 72.4 +/-
      7.3% (mean +/- standard deviation [SD]) in the HUCB samples. Several lectins were
      also used for processing HUCB and compared for their ability to remove RBC. Of
      these, soybean agglutinin (SBA) was found to remove RBC without substantial loss
      of HPC. Moreover, sequential treatment of HUCB with 3% gelatin and the AIS
      MicroCELLector SBA resulted in a product with < 1% hematocrit, 57% reduction in T
      cells, 35% nucleated cell recovery, and relatively high yields of burst-forming
      units-erythroid (BFU-E) (61%) and colony-forming units-granulocyte/macrophage
      (CFU-GM) (58%) and -mixed (CFU-GEMM) (66%). In a separate series of studies,
      enrichment of the CD34+ subset in HUCB was accomplished by processing HUCB with
      Ficoll followed by sequential treatment with the AIS MicroCELLector SBA and AIS
      MicroCELLector CD34. The CD34+ fraction was enriched for BFU-E (14-fold), CFU-GM
      (nine-fold), and CFU-GEMM (five-fold) with an overall purity ? > or = 92% CD34+
      by flow cytometry. This report demonstrates that 3% gelatin and the AIS
      MicroCELLector SBA can be combined as an ex vivo processing technique to reduce
      the volume of the HUCB product by depleting RBC and T cells while still
      maintaining a high recovery of HPC. Moreover, separation of highly enriched CD34+
      cells from HUCB is achievable and opens up the possibility of using CD34+ cells
      from HUCB for ex vivo progenitor cell expansion for transplantation, transfusion,
      and gene therapy.

PMID- 7523168
TI  - Granulocyte colony-stimulating factor induces selective elevations of progenitor
      cells in the peripheral blood of mice.
AB  - The absolute numbers and relative frequencies of progenitor cells in six
      nonerythroid lineages were monitored in the peripheral blood (PB), bone marrow
      (BM), and spleen of Balb/c mice during 8 days of granulocyte colony-stimulating
      factor (G-CSF) injections. G-CSF induced a dose-related increase, up to 570-fold,
      in progenitor cell numbers in the blood and up to 620-fold rise of these cells in
      the spleen. The relative frequency of megakaryocyte progenitor cells was
      significantly increased in the blood compared with values in the BM or spleen.
      Time-dependent variations were also observed in the relative frequencies of three
      lineages of progenitor cells in the blood (megakaryocyte, granulocyte, and
      macrophage), but not in the BM or spleen. The consistent differences induced in
      the relative frequencies of various progenitor cell types between the blood,
      marrow, and spleen were independent of G-CSF dose. These data suggest that the
      increase in progenitor cells in the blood induced by G-CSF cannot simply be
      explained by a nonselective release of progenitor cells from the marrow or
      spleen.

PMID- 7523171
TI  - Donor stromal cells support hematopoiesis in CFU-S colonies.
AB  - To examine the effect of hematopoietic stromal cells on bone marrow
      transplantation (BMT), CF-1 cells, which were previously established from splenic
      stroma of a mouse that was administered recombinant human granulocyte colony
      stimulating factor (rhG-CSF), were transplanted with bone marrow cells. The
      stromal cells were transfected with the plasmid DNA of beta-galactosidase (beta G
      CF-1) cells for studying immunohistochemistry. Using immunohistochemistry, the
      spleen and bone marrow of the recipient mice were examined for beta-galactosidase
      on the 8th and 12th day after BMT. In the spleen, beta G-CF-1 cells were observed
      within and in the regions immediately surrounding the colony-forming unit-spleen
      (CFU-S) on the 8th and 12th day after BMT. In certain regions, beta G-CF-1 cells
      existed in or surrounded the CFU-S colonies that consisted of the
      undifferentiated hematopoietic cells, while in other regions the granulopoiesis
      increased, especially in correspondence with the existence of beta G-CF-1 cells.
      In the bone marrow cavity, beta G-CF-1 cells were also recognized, though
      hematopoiesis was lower than the normal bone marrow. These data demonstrate that
      CF-1 cells, that is, donor stromal cells, can be transplanted to the
      hematopoietic organs and can then support hematopoiesis.

PMID- 7523170
TI  - Effects of rhG-CSF (filgrastim) on the recovery of hematopoiesis after high-dose
      chemotherapy and autologous peripheral blood stem cell transplantation in
      children: a report from the Children's Cancer and Leukemia Study Group of Japan.
AB  - In a nonrandomized study, hematopoietic recovery kinetics were evaluated in 98
      consecutive patients who underwent high-dose chemotherapy without total body
      irradiation (TBI) and autologous peripheral blood stem cell transplantation
      (PBSCT). Fifty-three patients received recombinant human granulocyte colony
      stimulating factor (rhG-CSF) (filgrastim) therapy after PBSCT, and the data were
      compared by actuarial analysis to those of 45 historic controls. The number of
      days required to achieve a white blood cell count (WBC) of 1 x 10(9)/L, an
      absolute granulocyte count (AGC) of 5 x 10(8)/L, and a platelet count (PLT) of 5
      x 10(10)/L were, respectively, 12.8 +/- 6.4 (mean +/- standard deviation [SD]),
      13.4 +/- 6.4, and 49.2 +/- 78.2 in treated patients vs. 12.8 +/- 4.6, 14.4 +/-
      10.3, and 31.4 +/- 38.8 days in historic controls, with no significant
      differences. There was no significant difference between the average number of
      days with fever in the treated group (6.0 +/- 6.6) and that in the control group
      (4.0 +/- 2.8). All febrile episodes responded promptly and successfully to
      parenteral antibiotic therapy. Thus, the data may suggest the possibility that
      therapy with filgrastim has only a limited ability to enhance hematopoietic
      recovery after PBSCT. To confirm this notion, we initiated a prospective
      randomized trial by recruiting a larger number of patients.

PMID- 7523174
TI  - The innervation of the mystacial pad in the adult rat studied by anterograde
      transport of HRP conjugates.
AB  - Peripheral and central terminations of mystacial pad afferents in rats were
      labeled by anterograde transport of wheat germ agglutinin-HRP (WGA-HRP) or
      choleragenoid HRP (B-HRP). Tracer was injected in the trigeminal ganglion and
      survival times were 6-24 h. Most of the innervation previously observed with
      other techniques in the mystacial pad were labeled by at least one of the
      tracers. This included extensive reticular endings from large-caliber afferents
      and a loose network of fine-caliber axons in vibrissal follicle-sinus complexes
      (F-SCs). Also included were individual highly branching bush-like profiles in the
      intervibrissal epidermis that arose from fine to medium caliber afferents. Other
      endings were revealed, such as beaded endings affiliated with tylotrich hairs and
      presumptive encapsulated lamellated endings affiliated with both vibrissae and
      small sinus hairs. Finally, the anterograde labeling also revealed differences in
      the branching pattern of Merkel afferents to the rete ridge collars and ring
      sinuses of F-SCs. Each tracer produced different patterns of labeling related to
      the survival time in the mystacial pad which corresponded to particular patterns
      of labeling in the trigeminal nucleus caudalis. WGA-HRP produced dense labeling
      of all types of afferents and peripheral endings as well as all laminae of
      nucleus caudalis after short survivals, but the labeling diffused as the survival
      times were increased. B-HRP preferentially filled the largest afferents and
      endings after shorter survivals, while smaller profiles became progressively
      labeled after longer survivals. In nucleus caudalis, profiles extending into
      laminae III, IV and inner part of lamina II were labeled with B-HRP after shorter
      survivals, but the outer part of lamina II also became labeled with longer
      survivals. This has not been previously observed with B-HRP. Along with other
      recent findings, these results reveal that the innervation of the mystacial pad
      especially by fine-caliber axons is far more extensive and complex than
      previously described. Also, depending on the survival time, the central and
      peripheral labeling patterns differ, which must be taken into account when
      interpreting results using these two tracers.

PMID- 7523169
TI  - Transitional changes in immunophenotypic subpopulations of human peripheral blood
      CD34+ cells expanded in vitro.
AB  - We determined the appropriate incubation period to expand human peripheral blood
      (PB) CD34+ cells for clinical application and the role of recombinant human (rh)
      interleukin-3 (rhIL-3) in the expansion and differentiation of these cells. The
      cells were purified up to 40 +/- 16% and transitional changes in immunophenotypic
      subpopulations in suspension culture were examined following stimulation with
      three different combinations of rh colony-stimulating factors (rhCSFs): 1) rhIL-3
      alone, 2) rhIL-6, rhSCF, rhG-CSF, plus rhGM-CSF, and 3) the four CSFs plus rhIL
      3. With all three CSF combinations, the total cells increased continuously after
      day 5 until day 14, and a combination of the five CSFs always gave rise to the
      highest number of total cells. Immunophenotypic analysis of the expanded cells
      showed that with all three CSF combinations CD34+ cells reached a maximal rate on
      day 5 and then decreased in an inverse correlation between the logarithm of CD34
      positive rate and the duration of suspension culture. The maximum expansion of
      CD34+ cells and PB progenitor cells (PBPC) with rhIL-3 alone, the four CSFs, or
      the five CSFs was observed on day 5, 10, or 7, respectively. The combination of
      the five CSFs was identified as the most potent stimulus for expansion of PBPC
      and CD34+ cells, as it increased non-erythroid PBPC 89 +/- 69-fold, with a range
      of 24 to 204-fold on day 7. However, differences in the expansion rate of these
      cells on days 5, 7, and 10 were not statistically significant. The majority of
      purified CD34+ cells coexpressed CD38 (91 +/- 3%) but were negative for CD33 (85
      +/- 4%), and one-half coexpressed CD13. With all three combinations of CSFs, the
      mature CD34+ cells that coexpressed CD38, CD33, or CD13 expanded in parallel with
      the total CD34+ cells, while an increase in relatively immature CD34+ cells,
      which do not express CD38, CD33, or CD13, was only statistically significant with
      the five CSFs. Thus, rhIL-3 played a critical role when combined with the four
      CSFs by increasing both mature and immature CD34+ cells.

PMID- 7523173
TI  - Input-output organization of the rat vibrissal motor cortex.
AB  - The afferent and efferent connections of the vibrissal area of the rat motor
      cortex (VMCx) were investigated by injecting Phaseolus vulgaris leucoagglutinin
      (PHA-L) or wheat germ agglutinin-horseradish peroxidase into the physiologically
      defined VMCx. The VMCx formed reciprocal connections with the primary and
      secondary somatosensory cortex, lateral and ventrolateral orbital cortex,
      retrosplenial cortex, and perirhinal cortex. These corticocortical afferents
      originated from cell bodies in layers II-III and V, and some afferents originated
      from cell bodies in layer VI of the primary sensory cortex. All of the VMCs
      efferents terminated in layers I and V or layers I-III and V. The VMCx also
      formed reciprocal connections with the ventrolateral, ventromedial and
      centrolateral nucleus, the lateral portion of the mediodorsal nucleus and the
      posterior complex of the thalamus. It projected bilaterally to the caudate
      putamen, primarily ipsilaterally to the superior colliculus, anterior pretectal
      nucleus, and pontine nucleus, and mainly contralaterally to the oral part of the
      spinotrigeminal nucleus and the reticular formation around the facial nerve
      nucleus. Finally, injections of PHA-L into the superior colliculus demonstrated
      that this structure projected contralaterally to the lateral part of the facial
      nerve nucleus. These data suggest that the VMCx plays a key role in sensorimotor
      integration, through its extensive interconnectivity with numerous brain
      structures, and may modulate orientation behaviors by relaying processed
      information to the superior colliculus.

PMID- 7523175
TI  - Dose-dependent effects of recombinant human NGF on grafted adult adrenal
      medullary tissue.
AB  - It has previously been shown that the chromaffin cells of the adrenal medulla
      respond to nerve growth factor (NGF) with neurite outgrowth and increased cell
      survival in tissue culture or after grafting. In the present study we evaluated
      the dose dependency in neurite outgrowth from chromaffin tissue to recombinant
      human NGF (rhNGF). Therefore, pieces of adrenal medullary tissue from adult rat
      were grafted into the anterior chamber of the eye of previously sympathectomized
      recepients. Survival time was 4 weeks. At grafting and at Days 7, 14, and 21
      postgrafting, the eyes were injected with 5 microliters of rhNGF at
      concentrations of 10, 30, 60, 100, 150, and 200 micrograms/ml, or with a control
      solution. All grafts, including the controls, survived well and became
      vascularized. At the low doses of rhNGF, 10 and 30 micrograms/ml, a small area of
      the irides was reinnervated and the density of the nerve fiber network was low.
      The maximal response was obtained at 100 micrograms rhNGF/ml. Using larger
      concentrations of 150 and 200 micrograms rhNGF/ml, the density of the nerve fiber
      network did not change, but the reinnervated area of the irides was significantly
      decreased compared to the outgrowth seen in irides treated with 100
      micrograms/ml. In conclusion, adult rat chromaffin tissue responds to rhNGF in a
      dose-dependent manner. However, at the highest doses used, the outgrowth area was
      suboptimal, although nerve fiber density was maximal. These results indicate that
      to obtain maximal effects, the dose of NGF is critical.

PMID- 7523172
TI  - Regeneration of dorsal root axons into experimentally altered glial environments
      in the rat spinal cord.
AB  - Exposure of the lumbar spinal cord of rats to X-rays 3 days after birth results
      in changes in the composition of central glia. Shortly after irradiation, there
      is both retardation of central myelin formation and a loss of integrity of the
      astrocyte-derived glia limitans on the dorsal surface of the cord. Subsequently,
      Schwann cells invade, undergo division and myelinate axons in the dorsal funiculi
      in the irradiated region of the cord, creating there an environment similar to
      that of peripheral nerve. The present study was undertaken to compare the ability
      of lesioned dorsal root axons to grow back into the altered glial environments
      that exist within the spinal cord after irradiation. This regrowth was assessed
      by injecting Fluoro-Gold into the spinal cord and subsequently examining neurons
      in the dorsal root ganglia (DRG) for the presence of this label. Numbers of
      retrogradely labeled neurons were counted in the DRG in both injured and
      contralateral non-injured sides. Non-irradiated control rats had almost no
      labeled DRG neurons on the injured side, whereas Fluoro-Gold labeled neurons were
      observed in substantial numbers in the DRG on the injured side of irradiated
      rats. There was a definite trend in the data, indicating that the longer the
      interval between irradiation and root injury, the greater the number of labeled
      neurons. Since the Fluoro-Gold labeling technique does not allow for
      visualization of the labeled axons within the spinal cord, a few animals were
      used to assess anterograde labeling with wheat germ agglutinin-conjugated
      horseradish peroxidase (WGA-HRP/HRP) from the dorsal root into the spinal
      cord.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523177
TI  - A method for in situ hybridization in wholemounted lamprey brain: neurofilament
      expression in larvae and adults.
AB  - Nonisotopic in situ hybridization (NISH) using both cDNA and cRNA probes is
      rapidly gaining favor over autoradiographic methods. Typically, either
      biotinylated or digoxigenin-labeled probes are used to detect mRNAs in sectioned
      tissue or in cultured cells. With a few exceptions, most applications of NISH in
      wholemount preparations have been limited to Drosophila embryos. A protocol
      developed for NISH in whole adult Drosophila CNS was extended to wholemounted
      larval and adult lamprey brain preparations. Digoxigenin-labeled RNA probes were
      transcribed from cloned fragments of a lamprey neurofilament (NF180) cDNA.
      Hybridization with these probes, and comparisons with Nissl-stained wholemounts
      and wholemounts retrogradely labeled by injections of tracer into the spinal
      cord, demonstrated that NF180 mRNA was expressed in only a subset of neurons in
      the lamprey CNS. These included primarily neurons with long axons that project
      out of the brainstem, e.g., reticulospinal neurons and cranial motor neurons.
      Metamorphosis from the larval to the adult form was accompanied by an increase in
      the number of neurons expressing NF180 and in the apparent level of NF expression
      as judged by the intensity of labeling. For example, in the oculomotor and
      trochlear nuclei, expression of NF180 was seen in postmetamorphic young adult
      lampreys but not in larvae. In the trigeminal motor nucleus, both the number of
      neurons expressing NF180 and the intensity of the hybridization labeling
      increased with metamorphosis. The ability to do NISH in lamprey brain wholemounts
      eliminates the need for serial reconstructions and thus facilitates the study of
      selected gene expression during metamorphosis and regeneration.

PMID- 7523178
TI  - Intrastriatal infusions of brain-derived neurotrophic factor: retrograde
      transport and colocalization with dopamine containing substantia nigra neurons in
      rat.
AB  - The pattern of retrogradely transported BDNF, a member of the nerve growth family
      of neurotrophins, following intrastriatal infusion was immunohistochemically
      visualized within the rodent central nervous system. Human recombinant BDNF was
      infused at a rate of 3 micrograms/h for 7 days with an Alzet 2002 minipump prior
      to sacrifice. Tissue immunohistochemically processed using a turkey anti-BDNF
      antibody revealed retrogradely transported BNDF within neurons located mainly
      within the ipsilateral frontoparietal cortex (predominantly layer V),
      parafascicular and posterior thalamic nuclei, and substantia nigra, pars
      compacta. Sections dual immunoreacted for BNNF and tyrosine hydroxylase revealed
      a subpopulation of dopaminergic neurons (approximately 28%) within the pars
      compacta which contained retrogradely transported BDNF. Experiments in which a
      mixture of BDNF and the retrograde tracer fluorogold were simultaneously infused
      for 7 days into the striatum revealed BDNF and fluorogold single-labeled neurons
      as well as BDNF and fluorogold dual-labeled cells within the substantia nigra,
      pars compacta. These observations indicate that only a subpopulation of neurons
      within the substantia nigra retrogradely transport BDNF following intrastriatal
      infusion and thus only a subpopulation of cells may be responsive to the trophic
      influences of BDNF. The retrograde transport of trophins, such as BDNF,
      represents a unique neuroanatomical tool to selectivity map the location of
      specific neurotrophin-responsive systems. Unraveling the trophic anatomy of BDNF
      will aid in understanding its role in development, degeneration, and experimental
      animal models of regeneration providing essential data for its use in clinical
      neurodegenerative disorders including Parkinson's disease.

PMID- 7523176
TI  - Selective up-regulation of neuropeptide synthesis by blocking the neuronal
      activity: galanin expression in septohippocampal neurons.
AB  - Neuronal activity regulates expression of phenotype-specific genes, including
      galanin, which coexists with choline acetyltransferase in septal and basal
      forebrain neurons. Transections of the fornix and the diagonal band alter galanin
      expression in septohippocampal neurons attributed to a deficit in target-derived
      trophic factors. The present study demonstrates that tetrodotoxin-induced
      blockade of neuronal activity fully mimicked the effect of axotomy (transection
      of the septohippocampal fibers) in the neurons of the nucleus of the diagonal
      band, and caused a dramatic, although temporary, up-regulation of galanin
      immunoreactivity and galanin mRNA without significant alteration in choline
      acetyltransferase expression. This finding suggests that in the septohippocampal
      cholinergic system perturbance of electrical activity alone can lead to temporary
      up-regulation of galanin expression, previously attributed exclusively to a
      "lesion effect."

PMID- 7523181
TI  - In vivo administration of granulocyte colony-stimulating factor promotes
      neutrophil survival in vitro.
AB  - We recently showed that recombinant human granulocyte-colony stimulating factor
      (rhG-CSF) maintained the viability of human neutrophils in incubation for up to
      72 hours. However, it is not known whether rhG-CSF can enhance neutrophil
      survival in in vivo situations. To clarify this issue, we investigated neutrophil
      survival in vitro following in vivo injection of rhG-CSF. Neutrophils were
      obtained from 4 pediatric patients with malignancies and healthy adult volunteers
      before and after rhG-CSF administration. Neutrophils obtained before rhG-CSF
      treatment started to undergo apoptosis after 24 h of incubation. In contrast, the
      survival of neutrophils drawn after rhG-CSF administration increased by
      approximately 24 h. Concomitantly, the appearance of typical ladder-like DNA
      fragmentation was delayed. Such an increase in neutrophil survival was inhibited
      by co-incubation with either H 7 (10 mumol/l) or H 8 (20 mumol/l), which worked
      as protein kinase C inhibitors. Although our study did not measure neutrophil
      survival in vivo directly, it provides us with further evidence that rhG-CSF may
      function to prolong neutrophil life expectancy in vivo.

PMID- 7523179
TI  - Cholecystokinin is not a major regulator in the digestive system in the chicken.
AB  - To find out whether physiological concentrations of cholecystokinin (CCK), a
      gastrointestinal hormone in mammals, are also active in chickens, the pancreatic
      amylase secretory response to CCK-8 was investigated in vitro. Rat pancreatic
      acini responded to the physiological concentration of CCK-8, but in chickens
      amylase release was induced at a concentration of CCK-8 1000 times higher than
      that observed in rats. In another experiment, biliary flow was tested with
      several doses of CCK-8. The bile flow was stimulated in a dose-dependent fashion,
      but a significant enhancement was not obtained at a concentration of 0.5
      micrograms CCK-8/kg body weight, which was considerably higher than physiological
      ones. It is concluded that endogenous CCK does not have an important role in the
      digestive system in the chicken.

PMID- 7523183
TI  - T cell epitope analysis with peptides simultaneously synthesized on cellulose
      membranes: fine mapping of two DQ dependent epitopes.
AB  - Several MHC class II restricted, CD4+ human T cell clones from three donors were
      induced with soluble matrix protein of influenza virus. The epitopes recognized
      by these clones were mapped using a complete set of overlapping 15-mer peptides
      synthesized with the newly developed SPOT method which allows the simple
      simultaneous synthesis of numerous peptides on cellulose membranes. Fine analysis
      of two clones by truncation of the stimulatory peptide by single subsequent amino
      acids from either the NH2- or the COOH-terminus revealed the minimal stimulatory
      determinants of two DQ dependent T cell epitopes.

PMID- 7523184
TI  - A homodimer represents an active species of the peptidyl-prolyl cis/trans
      isomerase FKBP25mem from Legionella pneumophila.
AB  - The molecular mass of the native FK506-binding peptidyl-prolyl cis/trans
      isomerase (PPIase) FKBP25mem from Legionella pneumophila (Mip (macrophage
      infectivity potentiator) protein) was determined by two methods. By gel
      permeation chromatography we found no indication of the presence of the monomeric
      enzyme. However, an oligomeric state with a molecular mass of about 62 kDa was
      detected. By cross-linking with dimethyl pimelimidate and subsequent SDS-PAGE of
      either the surface proteins of intact L. pneumophila cells or the purified
      recombinant FKBP25mem in solution, we observed an immunoreactive band indicative
      of a mass in the dimer range. In contrast to human recombinant FKBP12, the
      enzymatic activity of Legionella FKBP25men was strongly dependent on the protein
      concentration, pointing to a dimer as the most active species. However, the
      inhibition by FK506 yielded a nearly constant value of Ki of about 250 nM when
      measured in the same range of FKBP25mem concentration. These results may be
      explained by the fact that monomeric FKBP25mem has little, if any, influence on
      enzymatic activity when compared with the homodimer.

PMID- 7523182
TI  - Effects of cyclic AMP on expression of LFA-1, Mac-1, and VLA-4 and eosinophilic
      differentiation of a human leukemia cell line, EoL-1.
AB  - We examined the effect of dibutyryl cAMP (dbcAMP) on the expression of LFA-1
      (CD11a/CD18), Mac-1 (CD11b/CD18), and VLA-4 (CD49/CD29) and on eosinophilic
      differentiation of a human leukemia cell line, EoL-1. Dibutyryl cAMP induced
      eosinophilic differentiation of EoL-1 cells from 6-9 days after the start of
      culture with down-regulation of CD11a, CD18, and CD49 expression and up
      regulation of CD11b expression. Changes in integrin expression, except for CD18,
      were seen predominantly in the fraction containing eosinophilic granule-positive
      cells, suggesting that the changes were dependent on eosinophilic
      differentiation. On the other hand, dbcAMP-induced changes of integrin expression
      were reversible and were not seen on day 9 when dbcAMP was removed on day 3,
      whereas eosinophilic differentiation was still present. A combination of G-CSF
      and TNF-alpha, which also induced eosinophilic differentiation of EoL-1 cells,
      increased CD11b expression slightly but had no significant effect on the
      expression of the other integrins. Butyrate and PMA up-regulated CD11b expression
      without eosinophilic differentiation. The results collectively suggest that the
      regulation of integrin expression on EoL-1 cells is partly dependent and partly
      not dependent on eosinophilic differentiation. The possible involvement of
      protein kinase A and protein kinase C in these changes is suggested.

PMID- 7523185
TI  - Involvement of the brain type of ryanodine receptor in T-cell proliferation.
AB  - Cloning and sequence analysis of cDNA showed that the brain type of ryanodine
      receptor (RYR) is expressed in human Jurkat T-lymphocyte cells. Fura-2
      measurements revealed that the RYR in T-cells functions as a ryanodine-sensitive,
      caffeine-insensitive Ca2+ release channel. Furthermore, ryanodine stimulated
      proliferation and altered the growth pattern of cultured human T-cells when added
      together with FK506.

PMID- 7523190
TI  - Determination of the vitronectin binding site on plasminogen activator inhibitor
      1 (PAI-1).
AB  - Vitronectin is the carrier protein of plasminogen activator inhibitor 1 (PAI-1).
      We used a well-characterized panel of anti-human PAI-1 monoclonal antibodies
      (MoAbs) to localize the vitronectin-binding site on PAI-1. By employing a direct
      vitronectin/PAI-1 binding assay and two vitronectin-dependent inhibition assays,
      we demonstrate that the anti-PAI-1 MoAbs CLB-5, CLB-10, CLB-2C8 and I1, directed
      against different epitopes in the region between amino acids 110 and 145, prevent
      the interaction of PAI-1 with vitronectin. We conclude that the region between
      amino acids 110 and 145 of PAI-1 harbours an important determinant for the
      interaction with vitronectin.

PMID- 7523187
TI  - On the origin of the genetic code.
AB  - A series of stages in the evolution of the genetic code is postulated,
      representing a chain of logical steps that leads to the present-day code. The
      stages described are based on translation machinery between the RNA world and
      that of amino acids, a model that consists of an RNA assembler strand along which
      RNA hairpin molecules are lined up, forming a picket-fence-like aggregate. Each
      hairpin carries an amino acid at the bottom of one of its legs, and the mutual
      proximity of amino acids achieved in this way facilitates their linkage into
      oligopeptides, in a sequence governed by the nucleotide sequence along the
      assembler strand, the code. The order in which amino acids are introduced into
      the code is in the approximate order of their availability, tempered by polarity
      and structural considerations.

PMID- 7523188
TI  - Functional interaction between the epidermal growth factor receptor and c-Src
      kinase activity.
AB  - To study the relationship between the tyrosine kinase c-Src and the epidermal
      growth factor receptor (EGF-R), we used the breast cancer cell line ZR75-1, which
      was transfected with the EGF-R. The EGF-R transfected cell line expressed 60
      times more EGF-R than a control cell line transfected with the empty vector. In
      the presence of EGF, the EGF-R over-expressing cell line grew much faster than
      the control cell line. Both cell lines expressed approximately equal amounts of c
      Src. However, the cell line over-expressing the EGF-R showed a twofold
      enhancement of c-Src kinase activity after EGF stimulation. The activation of c
      Src kinase by EGF was confirmed in other EGF-R expressing cell types.

PMID- 7523189
TI  - Autophosphorylation-activated protein kinase inactivates the protein tyrosine
      phosphatase activity of protein phosphatase 2A.
AB  - Phosphorylation of the catalytic subunit of protein phosphatase 2A (PP2A) on
      threonines with a distinct autophosphorylation-activated protein kinase [Guo and
      Damuni (1993) Proc. Natl. Acad. Sci. USA 90, 2500-2504] inactivated the
      phosphatase with 32P-labelled myelin basic protein prepared by incubation with
      the kinase domain of the epidermal growth factor receptor, the src-family protein
      kinases p56lck and p60c-src, myelin basic protein kinase-1, or protamine kinase.
      Phosphoamino acid analysis demonstrated that the kinase domain of the epidermal
      growth factor receptor, p56lck and p60c-src phosphorylated myelin basic protein
      on tyrosines, that the protamine kinase phosphorylated myelin basic protein on
      serines, and that myelin basic protein kinase-1 phosphorylated myelin basic
      protein on threonines. The results demonstrate that the autophosphorylation
      activated protein kinase not only inactivates the protein serine/threonine
      phosphatase, but also the protein tyrosine phosphatase activity of PP2A. This
      autophosphorylation-activated protein kinase-mediated inactivation of PP2A may,
      in response to extracellular stimuli, not only contribute to the enhanced
      phosphorylation of cellular proteins on serines and threonines but also on
      tyrosines.

PMID- 7523191
TI  - Single channel activity of the ryanodine receptor calcium release channel is
      modulated by FK-506.
AB  - The immunosuppressant drug FK-506 (3-20 microM) increased the open probability of
      ryanodine receptor calcium release channels, formed by incorporation of terminal
      cisternae vesicles from rabbit skeletal muscle into lipid bilayers, with cis
      (cytoplasmic) calcium concentrations between 10(-7) M and 10(-3) M. FK-506
      increased mean current and channel open time and induced long sojourns at
      subconductance levels that were between 28% and 38% of the maximum conductance
      and were distinct from the ryanodine-induced subconductance level at about 45% of
      the maximum conductance. FK-506 relieved the Ca2+ inactivation of the ryanodine
      receptor seen at 10(-3) M Ca2+. The results are consistent with FK-506 removal of
      FK-506 binding protein from the ryanodine receptor.

PMID- 7523180
TI  - Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin
      6, and soluble interleukin-2 and -6 receptor concentrations in normal volunteers.
AB  - This study has been carried out in order to investigate seasonal variation in
      peripheral blood immune cells, such as leukocytes, monocytes, neutrophils,
      lymphocytes, CD3+ T, CD4+ T, CD8+ T, CD25+ T, CD20+ B, and serum interleukin-6
      (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R levels in normal volunteers.
      Toward this end, 26 normal volunteers (13 men, 13 women) had monthly blood
      samplings during one calendar year for peripheral blood count, flow cytometric
      enumeration of peripheral leukocyte subsets and immunoassays of IL-6, sIL-6R and
      sIL-2R. It was found that most of the immune variables change rhythmically during
      the seasons as a group phenomenon. Statistically significant yearly variations
      with seasonal rhythms, i.e. annual rhythms or harmonics, such as semiannual,
      tetramensual and trimensual rhythms, were found in the number of leukocytes,
      neutrophils, monocytes, lymphocytes, CD4+ T, CD8+ T, CD25+ T, CD20+ B cells, in
      the CD4+/CD8+ ratio, and serum IL-6 and sIL-6R levels. It is concluded that the
      immune system is characterized by a multifrequency time-structure with
      significant high-amplitude yearly variations in the number of some peripheral
      blood leukocyte subsets.

PMID- 7523192
TI  - Immunoreactivity of chimeric proteins carrying the HIV-1 epitope IGPGRAF.
      Correlation between predicted conformation and antigenicity.
AB  - Sera from HIV-1 infected individuals were examined for their reactivity to the
      principal neutralizing domain, IGPGRAF sequence, of the V3-loop of HIV-1. Four
      hybrid proteins carrying this sequence inserted in four different outer loops of
      a protein that makes up the capsid of an insect virus were used as antigen in a
      Western blot assay for this survey. All the four antigens showed different
      activity: sera that recognise all antigens to sera that reacted with only one of
      them. Competition experiments indicated that the antibodies recognised these
      proteins with different affinity. Molecular modelling of the hybrid proteins
      predicted that the inserted sequence adopted different conformations in each
      position. Comparison of predicted most stable conformations for IGPGRAF indicated
      that there is a close relationship between conformational similarity to a V3-loop
      reference structure and the degree of reactivity with sera.

PMID- 7523186
TI  - Susceptibility of tenascin to degradation by matrix metalloproteinases and serine
      proteinases.
AB  - The degradation of tenascin purified from human melanoma cells was examined by
      treatment with matrix metalloproteinases (MMPs) and serine proteinases. Among
      eight different types of proteinases examined, MMP-1, -3, and -7, cathepsin G and
      leukocyte elastase could digest tenascin, but MMP-2, MMP-9 and thrombin did not.
      This suggests that tenascin may be readily catabolized by extracellular matrix
      degrading proteinases found in the pathophysiological conditions.

PMID- 7523193
TI  - Isolation and characterization of mutants of human mitogen-activated protein
      kinase (ERK2).
AB  - Site directed mutagenesis/charged-to-alanine scanning mutagenesis of the amino
      terminal portion of human ERK2 (from amino acids 1 to 150) purified as a
      glutathione-S-transferase fusion protein (GST-ERK2) from E. coli has been done to
      determine regions/amino acids important for activation by rabbit skeletal muscle
      MAP kinase kinase (rMEK) and kinase activity towards myelin basic protein (MBP).
      Five classes of mutants have been isolated. The first class of mutants comprises
      of G30A/G32A, A50D and R65A/R68A/E69A, that can be phosphorylated by rMEK and
      have no kinase activity towards MBP, the second class includes mutants
      D122A/H123A and N142A which have lower kinase activities but no change in their
      activation by rMEK; third class being Y34A, E58A/H59A, which have neutral effect
      towards either activity, the fourth class that includes completely inactive
      mutants D42A/K46A/R48A, the deletion mutant in the same region (-9aa[40-48]) and
      D104A/E107A/D109A and finally the fifth class that include K53A, E94A/K97A/D99A,
      K112A/K115A and R133A/K136A that are phosphorylated 140-240% but with kinase
      activity toward MBP ranging from 50-100% of the wild type.

PMID- 7523195
TI  - Collagen stimulates tyrosine phosphorylation of phospholipase C-gamma 2 but not
      phospholipase C-gamma 1 in human platelets.
AB  - Collagen is an important primary stimulus of platelets during the process of
      hemostasis. As with many other platelet stimuli, collagen signal transduction
      involves the hydrolysis of inositol phospholipids; however, the mechanisms which
      underlies this event is not well understood. Neither the collagen receptor nor
      the isoform of phospholipase C that is activated have been identified. We report
      that collagen-activation of platelets induces tyrosine phosphorylation of
      phospholipase C-gamma 2 but not phospholipase C-gamma 1. We also show that the
      platelet low affinity Fc receptor (Fc gamma RII), which mediates activation of
      platelets by immune complexes, and wheat germ agglutinin, which binds non
      specifically to glycoprotein, stimulate phospholipase C-gamma 2 tyrosine
      phosphorylation. In contrast, we could not detect phospholipase C-gamma 2
      tyrosine phosphorylation in platelets stimulated by either thrombin or a stable
      thromboxane A2 analogue, U46619.

PMID- 7523194
TI  - Olomoucine, an inhibitor of the cdc2/cdk2 kinases activity, blocks plant cells at
      the G1 to S and G2 to M cell cycle transitions.
AB  - The cdc2/cdk2 protein kinases play key roles in the cell cycle at two control
      points: the G1/S transition and the entry into mitosis. Olomoucine, a specific
      inhibitor of these kinases, was tested in two plant cell systems: Petunia
      mesophyll protoplasts induced to divide and Arabidopsis thaliana cell suspension
      cultures. The cell cycle status was analysed from DNA histograms or through
      continuous labelling of cells with 5-bromodeoxyuridine (BrdUrd) followed by
      double staining with bis-benzimide (Hoechst 33258) and propidium iodide (PI).
      Such analyses resolve cells from several generations according to the extent of
      their DNA replication. Olomoucine was shown to reversibly arrest differentiated
      Petunia cells induced to divide at G1 phase and cycling Arabidopsis cells in late
      G1 and G2. A comparison of the effects of aphidicolin, oryzalin and olomoucine
      suggests that in the Arabidopsis cell suspension culture, a cdc2/cdk2-like kinase
      is activated at a restriction point in late G1.

PMID- 7523196
TI  - Phorbol 12-myristate 13-acetic acid inhibits PTP1B activity in human mesangial
      cells. A possible mechanism of enhanced tyrosine phosphorylation.
AB  - Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetic acid (PMA)
      stimulates DNA synthesis in human glomerular mesangial cells. Incubation of these
      cells with PMA stimulates the tyrosine phosphorylation of a set of proteins
      ranging from 110 to 39 kDa with different time kinetics. PMA inhibits total
      protein tyrosine phosphatase (PTPase) activity in these cells.
      Immunoprecipitation of PTP1B, an intracytoplasmic tyrosine phosphatase, with
      subsequent assay of the immunobeads for PTPase shows a significant inhibition of
      its activity in PMA-treated cells. Immunoblot analysis of mesangial cell lysates
      using the same antibody revealed that PMA does not affect the level of this 50
      kDa PTP1B protein. These data indicate that inhibition of total PTPase, and
      specifically PTP1B, activity may provide a mechanism for stimulation of tyrosine
      phosphorylation by PMA in these cells and thereby contribute to its mitogenic
      effect.

PMID- 7523197
TI  - Activation of the mouse cytokeratin A (endo A) gene in teratocarcinoma F9 cells
      by the histone deacetylase inhibitor Trichostatin A.
AB  - Treatment of cultured cells with sodium butyrate, that is the histone deacetylase
      inhibitor, induces the histone hyperacetylation and the expressions of various
      mammalian genes without affecting the level of protein synthesis. However,
      butyrate is a non-specific inhibitor of deacetylase because of its effects on
      various other enzymes and nuclear proteins other than histones. On the other
      hand, Trichostatin A (TSA) was recently found to be a potent and specific
      inhibitor of histone deacetylase. We examined the effect of TSA on the expression
      of mouse cytokeratin A (endo A). TSA increased endoA expression in F9 cells, and
      was effective at a much lower concentration than sodium butyrate. We also
      examined the changes of chromatin structure induced by the two drugs by a DNase I
      hypersensitivity assay. Both drugs induced the formation of a DNase I
      hypersensitive site (DH site) in only the promoter region. The precise
      mechanism(s) by which the two drugs increase endoA gene expression is unknown,
      but these results suggest that endoA expression is induced by inhibition of
      histone deacetylase and that the effect is at the transcriptional level.

PMID- 7523198
TI  - Palliative surgical treatment of malignant obstructive jaundice.
AB  - One-hundred-and-forty-five cases of malignant obstructive jaundice were seen from
      January 1989-December 1992. Carcinoma gallbladder (74/145) and carcinoma pancreas
      (67/145) were the two common causes. Fifty patients underwent a palliative
      surgical biliary bypass procedure. Jaundice was present in all the patients.
      Pruritus (40/50), cholangitis (17/50) and gastric outlet obstruction (11/50) were
      the other predominant symptoms which required palliation. Surgical palliation was
      achieved with a morbidity and mortality of 38% and 8%, respectively. Jaundice,
      pruritus and cholangitis were relieved in 92%, 88% and 88%, respectively. All
      patients with gastric outlet obstruction had complete relief. The mean hospital
      stay was 18.5 days. The mean survival was 6.5 months and 8.6 months for carcinoma
      gallbladder and carcinoma pancreas, respectively.

PMID- 7523199
TI  - Immunohistochemical analysis of estrogen and progesterone receptors in
      endometrium and peritoneal endometriosis: a new quantitative method.
AB  - OBJECTIVE: To evaluate estrogen receptors (ER) and progesterone receptors (PR)
      content in glandular and stromal cells of eutopic and ectopic endometrium.
      DESIGN: A recently advanced stereographic computer technology was applied for the
      investigation of steroid receptors. SETTING: University hospital department of
      gynecology. PATIENTS: Biopsies of endometrium and typical peritoneal
      endometriotic lesions were taken from 19 infertile patients with laparoscopically
      proved endometriosis. Endometrial biopsies were also taken from 15 patients
      without endometriosis. All of them were untreated. RESULTS: In normal
      endometrium, the highest concentrations of ER and PR occurred in the epithelial
      and stromal cells during the late proliferative phase of the menstrual cycle.
      Estrogen receptor and PR content declined throughout the secretory phase.
      Progesterone receptor content was found not to be significantly decreased in the
      stroma during the early secretory phase and quite high in the late secretory
      phase. In peritoneal endometriotic lesions, the highest concentrations of ER and
      PR were found during the late proliferative phase. When compared with normal
      endometrium, a lower ER content ans a similar PR content were observed, and the
      cyclic changes in peritoneal endometriosis lesions were also similar. CONCLUSION:
      A new computerized technology for the evaluation of ER and PR in eutopic and
      ectopic endometrium. Although the ER content was found to be lower in
      endometriotic tissue when compared with endometrium, the cyclic pattern was
      similar in both eutopic and ectopic endometrium. Progesterone receptor content
      was similar in both tissues, except during the late secretory phase in ectopic
      glandular epithelium in which a high persistent PR content was observed.

PMID- 7523200
TI  - Increases in progesterone after human chorionic gonadotropin administration may
      predict cycle outcome in patients undergoing in vitro fertilization-embryo
      transfer.
AB  - In this study, both IVF-ET cycle and pregnancy outcome were compared with
      increases seen in P concentration during the 24-hour period from 12 hours before
      to 12 hours after hCG administration. A significantly higher PR (P < 0.001) was
      seen in women who had at least a threefold increase in P during this time period.
      Further, no pregnancies were reported from women with a less than twofold
      increase in P.

PMID- 7523202
TI  - Maternal and perinatal outcome in thyrotoxicosis complicating pregnancy.
AB  - In this report we describe 32 pregnancies complicated by hyperthyroidism cared
      for over a 7-year period at AIIMS, New Delhi. In 6 cases hyperthyroidism was
      diagnosed during pregnancy; others were diagnosed before conception and were on
      antithyroid therapy during pregnancy. For control of thyrotoxicosis thiourea
      derivatives, carbimazole (CMZ) and propylthiouracil (PTU), were both used. The
      dosage of antithyroid drugs could be decreased or stopped in the third trimester
      in only 28% cases, while 50% cases did not require any change in the dosage
      during gestation and 21% required an increase in dosage with advancing gestation
      to control thyrotoxicosis. Maternal and fetal complications included preterm
      labour (25%), PIH (22%), thyroid crisis (9%) and intrauterine growth retardation
      (13%). Thyroid status of neonates was found abnormal in 9% cases, including 1
      case (3%) of neonatal thyrotoxicosis with goitre and 2 (6%) cases of neonatal
      hypothyroidism. One maternal death occurred due to thyroid storm. No case of
      stillbirth or perinatal death occurred in the present study. In our experience of
      32 cases maternal and fetal complications are reported with increased frequency,
      requiring close surveillance of thyroid status to maintain euthyroidism and
      intensive fetal monitoring during pregnancy to achieve good maternal and
      perinatal outcome.

PMID- 7523201
TI  - The role of genomic imprinting in implantation.
AB  - OBJECTIVES: To outline the possible role of the imprinted genes in early human
      embryogenesis and implantation. DATA IDENTIFICATION: Literature review. STUDY
      SELECTION: Studies examining the issues of genomic imprinting, implantation,
      gestational trophoblastic diseases, placental gene expression, and trophoblast
      invasion. RESULTS: Certain genes have been shown to be expressed either in the
      embryo or in the uterine decidua before implantation. Some of these have been
      shown to be parentally imprinted, that is, expressed either from their paternal
      or maternal origin. The paternally expressed genes are linked to placental
      proliferation and invasiveness. CONCLUSIONS: Clinical and basic data from
      different disciplines indicate that genomic imprinting may be crucial to the
      process of implantation.

PMID- 7523204
TI  - IGF-I-induced IGFBP-3 potentiates the mitogenic actions of IGF-I in mammary
      epithelial MD-IGF-I cells.
AB  - Limited information is available concerning the molecular and cellular mechanisms
      that regulate expression of insulin-like growth factor-I (IGF-I) binding proteins
      (IGFBPs) in bovine mammary epithelial cells. Here, we report on the autocrine
      mechanisms of action of IGF-I and hormonal regulation of expression of IGFBPs in
      bovine mammary epithelial MD-IGF-I cells which express recombinant IGF-I under
      the control of the glucocorticoid-inducible mouse mammary tumor virus-long
      terminal repeat (MMTV-LTR). Levels of IGFBP-3 mRNA and secretion of IGFBP-3 by MD
      IGF-I cells were stimulated by IGF-I, insulin (INS), and IGF-I analogs but not
      prolactin (PRL). Conversely, parental MAC-T cells expressed little IGF-I and
      secreted primarily IGFBP-2 (29-32 kDa) in response to stimulation with INS,
      dexamethasone (DEX), or IGF-I analogs. Secretion of recombinant IGF-I caused a
      26.5-fold increase in secretion of IGFBP-3, as measured by densitometric analysis
      of ligand blots, which was associated with a 1.7-fold increase in total DNA.
      Conditioned media (CM) from MD-IGF-I cells induced with DEX stimulated a 2.8-fold
      increase in [3H]thymidine incorporation into DNA of parental MAC-T cells,
      compared with uninduced cells. Moreover, inclusion of exogenous IGF-I with CM
      from MD-IGF-I cells triggered an additional 3.0-fold increase in label
      incorporation, but only a 1.6-fold increase in the presence of IGFBP-2-containing
      media conditions by MAC-T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523203
TI  - Loss of biological activity of human chorionic gonadotropin (hCG) by the amino
      acid substitution on the "CMGCC" region of the alpha-subunit.
AB  - In order to study the bioactive sites of the glycoprotein hormones, we have
      prepared five point mutants on the CMGCC (Cys28-Met29-Gly30-Cys31-Cys32) region
      of the human alpha-subunit by using site-directed mutagenesis. Each mutant human
      chorionic gonadotropin (hCG) agr; cDNA and a wild-type hCG beta cDNA were
      transcribed by T3 RNA polymerase, and the mixture of the hCG alpha mRNA and hCG
      beta mRNA was microinjected into Xenopus laevis oocytes. All five mutant hCGs
      produced in oocyte culture supernatants were detected as immunoreactive forms by
      enzyme immunoassay. In contrast, four mutants (Cys28-->Tyr28, Gly30-->Arg30,
      Ala30, Asp30) were devoid of biological activity in vitro bioassay using the
      production of testosterone with mouse Leydig cells. These results indicate that
      the CMGCC region in the alpha-subunit, particularly the cysteine residue at
      position 28 and the glycine residue at position 30, plays an important role in
      the biosynthesis of glycoprotein hormones.

PMID- 7523205
TI  - Involvement of cAMP and cGMP in the mode of action of molt-inhibiting hormone
      (MIH) a neuropeptide which inhibits steroidogenesis in a crab.
AB  - In crustaceans, production of molting hormones (or ecdysteroids) by the molting
      glands (Y-organs; YO), is under negative control exerted by a neuropeptide, the
      molt-inhibiting hormone (MIH). MIH of the crab Carcinus maenas inhibits in vitro
      steroidogenesis of basal (intermolt crab) or activated (premolt crab) YO. MIH
      inhibits secretion of the two ecdysteroids synthesized by crab YO, ecdysone (E)
      secreted throughout the molting cycle, and 25-deoxyecdysone (25dE), secreted
      during the premolt period. At a MIH concentration of 10(-8) M, E is reduced about
      50% and 25dE 94%. Regardless of the molting stage, this inhibition of
      steroidogenesis is reversible, dose dependent and measurable after 5 min. On
      intermolt YO, MIH induced cGMP increase and 8BrcGMP mimics the effect of MIH: at
      this stage cGMP seems to be involved with MIH inhibition of steroidogenesis. On
      premolt YO MIH induced a transient increase of cAMP (2-fold) and a long-lasting
      enhancement of cGMP (60-fold). On active YO, we demonstrated that a low
      concentration (10(-5) M) of dbcAMP, 8BrcAMP, 8BrcGMP, or agents increasing
      intracellular cAMP, mimic MIH effects and inhibit steroidogenesis. From these
      observations it is concluded that both cyclic nucleotides are involved in the
      mode of action of MIH on activated YO. At this premolt period, MIH/cAMP may act
      cooperatively with MIH/cGMP in the inhibitory control of steroidogenesis by crab
      YO.

PMID- 7523206
TI  - Second messenger regulation of mouse gonadotropin-releasing hormone gene
      expression in immortalized mouse hypothalamic GT1-3 cells.
AB  - Using a transgenic mouse derived GnRH expressing neuronal cell line, GT1-3, we
      studied the effects of activation of cAMP, Ca2+ and protein kinase C pathways by
      forskolin, ionomycin and the phorbol ester phorbol 12-myristate 13-acetate (PMA),
      respectively, upon gonadotropin-releasing hormone (GnRH) secretion, cellular
      peptide content, mRNA and RNA primary transcript levels. Forskolin, ionomycin and
      phorbol ester all caused an increase in GnRH secretion in GT1-3 cells in a time
      and dose-dependent manner during a short-term (1 h) static incubation. Prolonged
      treatment with forskolin (10 microM), ionomycin (1 microM) and PMA (10 nM) for 12
      or 24 h resulted in significant decreases in GnRH mRNA levels. Time-course
      studies showed that the increases in GnRH secretion stimulated by forskolin,
      ionomycin and PMA were gradually attenuated over time in parallel with the
      decreases in mRNA expression. In contrast, there were only small and variable
      changes in the GnRH cellular content. Studies using a GnRH antagonist (100
      microM) suggested that the released GnRH has a negative feedback effect on its
      own secretion. However, co-incubation with the GnRH antagonist did not alter the
      inhibitory effects on GnRH mRNA levels by the secretagogues. Further studies on
      the transcriptional effects of forskolin, ionomycin and PMA on GnRH gene
      expression in GT1-3 cells revealed that all three secretagogues suppressed GnRH
      RNA primary transcript levels, with forskolin having a slower time course of
      action. Thus, the inhibition of cytoplasmic GnRH mRNA, and presumably its
      synthesis, after 12-24 h of secretagogue treatment may be due at least in part to
      a suppression of GnRH gene transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523208
TI  - Cytokeratins as markers of ductal cell differentiation and islet neogenesis in
      the neonatal rat pancreas.
AB  - Cytokeratins (CKs) serve as immunocytochemical markers of epithelial cells. We
      found that duct cells of the neonatal and adult rat pancreas express CKs 7, 19,
      and 20. Because pancreatic endocrine cells are thought to derive from duct cells,
      we examined their expression of CKs 7, 19, and 20 during the neonatal period and
      the proliferative activity of the different cell types in and around islets.
      Immunocytochemical analysis revealed that the islets of the neonatal pancreas, in
      contrast to those of adults, strongly expressed CKs 7, 19, and 20, particularly
      within a peripheral mantle zone that was continuous with the epithelium of
      adjacent ductules. This pattern was found during the first 2 weeks of life when
      significant islet growth occurred as determined by morphometry and
      bromodeoxyuridine (BrdU) labeling. Moreover, BrdU labeling kinetics indicated
      that the growth of neonatal islets occurred in the peripheral mantle region
      characterized by intense CK20 and CK19 immunoreactivity and not in the region
      composed of differentiated endocrine cells. These observations strongly suggest
      that proliferating ductal cells associated with islets represent a pool of islet
      beta- and non-beta-precursor cells.

PMID- 7523207
TI  - Antibodies to glutamic acid decarboxylase and P2-C peptides in sera from
      coxsackie virus B4-infected mice and IDDM patients.
AB  - The possible role of amino acid sequence and epitope homologies between a protein
      P2-C of Coxsackie virus B4 and human GAD in the development of host-specific
      immune response in insulin-dependent diabetes mellitus (IDDM) (molecular mimicry)
      was investigated. Peptide antibodies to the P2-C protein, GAD65, and GAD67 were
      raised to analyze their immunoreactivity by enzyme-linked immunosorbent assay and
      immunoblotting with GAD purified from the brain and pancreas of mice that develop
      hyperglycemia after the infection. Additionally, antibody reactivity to these
      peptide antigens was assessed in sera from the virus-infected mice and IDDM
      patients. All three peptide antisera reacted very strongly with homologous
      peptides; P2-C antiserum cross-reacted with GAD65 as efficiently as GAD65
      antiserum with P2-C, but no cross-reaction was detected between P2-C and GAD67
      although cross-reaction between the two GADs was quite pronounced. P2-C antiserum
      immunocomplexed with GAD65 from mouse brain or pancreas, whereas GAD65 and GAD67
      antisera both immunocomplexed with the two GADs from these sources. Most of the
      sera from virus-infected mice were reactive to brain and pancreas GAD65 and also
      to P2-C peptide, whereas some reacted to GAD65 and a few to GAD67 peptides. A
      number of IDDM sera reacted with mouse GAD65 and also with P2-C and GAD65
      peptides, whereas only a few reacted with GAD67 peptide. The immunoreactivity of
      the mouse and IDDM sera to P2-C and GAD65 peptides was blocked by pre-adsorption
      with mouse GAD. The results suggest that molecular mimicry may play a role in the
      pathogenesis of the disease.

PMID- 7523209
TI  - Changing role of child neurology.

PMID- 7523210
TI  - Introducing a procedure using videotape instruction: the case of the lateral
      birth position.
AB  - BACKGROUND: Videotapes have been variably successful in teaching physical
      examination skills, interviewing strategies, and clinically relevant didactic
      material to medical students, residents, and physicians. The literature does not
      include evaluations of their success in introducing procedural techniques into
      clinical practice. OBJECTIVES: This study assessed whether the presentation of an
      instructional videotape influenced the adoption of a specific technique,
      assisting birth in the lateral position. METHODS: Family practice residents,
      faculty, and physicians participated in educational presentations that reviewed
      how to assist childbirth in the lateral position. Three different formats were
      used for the presentations; an instructional videotape formed the core element of
      each presentation. Immediately following the presentations, and on one other
      occasion 4-6 months later, the participating physicians received questionnaires
      surveying their use of the lateral birth position. RESULTS: Approximately 30% of
      the respondents who had not previously used the position used the lateral birth
      technique. Of the remaining respondents who had not used the technique, 64%
      considered using the technique with their laboring patients. Physicians who
      viewed the videotape in concert with other educational interventions were more
      likely to have adopted the new birth technique (P = .03). CONCLUSIONS: An
      instructional videotape, as part of a structured, interactive presentation, can
      be used successfully to introduce a procedure into the clinical practices of
      family physicians.

PMID- 7523211
TI  - [Asklepios once again at the National Academy of Medicine].

PMID- 7523213
TI  - Inhibition of endothelial-derived nitric oxide promotes P-selectin expression and
      actions in the rat microcirculation.
AB  - BACKGROUND/AIMS: Inhibition of nitric oxide synthesis increases leukocyte and
      endothelial interaction in mesenteric venules. In this study, the relationship
      between inhibition of NO and expression of the adhesion molecule P-selectin was
      examined. METHODS: The rat mesentery was superfused with the NO inhibitor NG
      nitro-L-arginine methyl ester (L-NAME) either alone or in combination with
      intravenous infusions of L-arginine, D-arginine, a P-selectin-neutralizing
      monoclonal antibody (PB1.3 [1 mg/kg]), recombinant human superoxide dismutase
      (hSOD), or 8 bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP). Leukocyte
      rolling and adherence were monitored in mesenteric venules via intravital
      microscopy. Ileal tissue superfused with L-NAME was examined
      immunohistochemically for P-selectin expression. RESULTS: Superfusion of the rat
      mesentery with L-NAME resulted in a significant increase in leukocyte rolling and
      adherence in the mesenteric venule, which was attenuated by administration of L
      arginine but not D-arginine. Monoclonal antibody PB1.3 as well as hSOD and 8-br
      cGMP administered before initiation of L-NAME superfusion significantly
      attenuated the increase in leukocyte rolling and adherence. Immunohistochemistry
      showed a significant increase in P-selectin expression after 60 minutes of
      superfusion with L-NAME, which was attenuated by L-arginine, hSOD, and 8-br-cGMP.
      CONCLUSIONS: These data indicate an important functional relationship between
      endothelial-derived NO production and expression of the endothelial adhesion
      molecule P-selectin.

PMID- 7523212
TI  - TP53 gene mutations and p53 protein immunoreactivity in malignant and
      premalignant Barrett's esophagus.
AB  - BACKGROUND/AIMS: Limited data are available regarding TP53 gene alterations in
      Barrett's esophagus. This study was undertaken to characterize TP53 mutations and
      p53 protein immunoreactivity in cancers and preinvasive lesions of Barrett's
      esophageal mucosa. METHODS: Seventeen Barrett's adenocarcinomas were examined by
      polymerase chain reaction amplification, denaturant gradient gel electrophoresis,
      and sequencing for the presence of TP53 mutations in exons 5-8. In 9 cases,
      Barrett's epithelium adjacent to the cancer was investigated. p53 protein
      immunoreactivity was studied with PAb 1801. RESULTS: Sixteen mutations were found
      in 15 adenocarcinomas, including 10 missense, 3 nonsense, 1 frameshift, and 2
      mutations located within consensus splice donor and acceptor sequences. All
      nucleotide substitutions were transitions. Eight of the 12 transitions involving
      a GC base pair occurred within the context of a CpG dinucleotide. p53
      immunostaining was present in all 10 cases with missense mutations and in 1 case
      without a detectable mutation. The surrounding Barrett's mucosa showed TP53
      mutations identical to that observed in the carcinoma in only 3 of 5 specimens
      showing high-grade dysplasia. CONCLUSIONS: TP53 gene mutations and p53 protein
      immunostaining are present in a majority of Barrett's adenocarcinomas. Our
      results suggest that these mutations are involved at an early stage during
      malignant transformation of Barrett's esophagus.

PMID- 7523214
TI  - The somatostatin receptor subtype on rat enterochromaffinlike cells.
AB  - BACKGROUND/AIMS: Gastric enterochromaffinlike (ECL) cells play an important role
      in peripheral regulation of acid secretion. This study investigated the
      somatostatin receptor subtype on ECL cells. METHODS: ECL cells were isolated from
      rat fundic mucosa to a purity of 90%-95% by combining enzymatic digestion,
      elutriation, density gradient centrifugation, and culture. RESULTS: Polymerase
      chain reaction performed with templates from an ECL cell complementary DNA
      library and primers specific to each of the five known somatostatin receptor
      subtypes showed that the somatostatin receptor type 2 was significantly enriched
      in ECL complementary DNA. Single cell videoimaging of highly purified ECL cells
      in culture showed that only the somatostatin receptor type 2 selective agonist,
      DC 32-87, inhibited the gastrin-induced calcium signal at 10(-11) mol/L. The type
      3 and type 4 selective agonists, DC 25-12 and DC 32-92, and also somatostatin 14
      required 100-1000 times higher concentrations (10(-8) mol/L). The somatostatin
      receptor type 2 analogue also inhibited gastrin-stimulated histamine release with
      a 50% inhibitory concentration (IC50) value of 2 x 10(-12) mol/L, whereas
      somatostatin 14 and the type 3 and 4 analogues showed IC50 values of 1 to 5 x 10(
      9) mol/L. CONCLUSIONS: The predominant somatostatin receptors on rat gastric ECL
      cells are of the somatostatin receptor 2 subtype; they inhibit histamine
      secretion by interfering with the gastrin-induced calcium signal.

PMID- 7523215
TI  - Vascular hyporesponsiveness to endothelin 1 in rats with cirrhosis.
AB  - BACKGROUND/AIMS: Because the vasodilator nitric oxide is overproduced in
      cirrhosis, this substance may decrease pressor responses to the vasoconstrictor
      endothelin 1. This study aimed to examine the effects of a NO synthesis inhibitor
      (NG-nitro-L-arginine methyl ester; L-NAME) on vascular responsiveness to
      endothelin 1 in normal and cirrhotic rats. METHODS: Pressor dose-response curves
      to endothelin 1 (0.5, 1, 3, 6, and 10 micrograms/kg intravenously) were obtained
      in animals with or without pretreatment with L-NAME. RESULTS: Pressor responses
      to endothelin 1 alone were significantly lower in cirrhotic than in normal rats.
      In cirrhotic animals, pressor responses to 3, 6, and 10 micrograms/kg of
      endothelin 1 were significantly higher in the presence than in the absence of L
      NAME. The responses to the other doses of endothelin 1 were not affected by L
      NAME. In normal rats, pressor responses to all doses of endothelin 1 were
      significantly higher in the presence than in the absence of L-NAME. In animals
      pretreated with L-NAME, pressor responses to 6 and 10 micrograms/kg of endothelin
      1 did not differ between cirrhotic and normal rats, whereas responses to other
      doses remained lower in cirrhotic than in normal rats. CONCLUSIONS: In rats with
      cirrhosis, NO seems to contribute to vascular hyporeactivity to high doses but
      not to low doses of endothelin 1.

PMID- 7523217
TI  - Nonalcoholic steatohepatitis: an expanded clinical entity.
AB  - BACKGROUND/AIMS: In the past, nonalcoholic steatohepatitis has been described
      mostly in obese women with diabetes. The aim of this study was to describe a
      series of patients with nonalcoholic steatohepatitis with a different clinical
      profile. METHODS: The clinical, biochemical, and histological features of 33
      patients with nonalcoholic steatohepatitis seen from July 1990 to June 1993 were
      analyzed. RESULTS: The mean age was 47 years. All patients were antibody to
      hepatitis C virus-negative. Nineteen of 33 (58%) were men, 20 of 33 (61%) were
      nonobese, 26 of 33 (79%) had normal glucose levels, and 26 of 33 (79%) had normal
      lipid levels. Fourteen of 33 (42%) had normal glucose and lipid levels and were
      not obese. Thirteen of 33 (39%) had pathological increases in fibrosis, 5 of whom
      had micronodular cirrhosis. Of these 13 with severe, progressive disease, 8 (62%)
      were women, 8 (62%) were obese, 4 (31%) were diabetic or had an elevated glucose
      level, and 3 (23%) had hyperlipidemia. Although serum iron studies (transferrin
      saturation and ferritin) were abnormal in 18 of 31 (58%), no patient had
      hemochromatosis. CONCLUSIONS: Nonalcoholic steatohepatitis can be a severe,
      progressive liver disease leading to the development of cirrhosis. It should no
      longer be considered a disease predominantly seen in obese women with diabetes.

PMID- 7523216
TI  - Expression of cytokine-dependent adhesion molecules in postreperfusion biopsy
      specimens of liver allografts.
AB  - BACKGROUND/AIMS: Allogeneic recognition of donor cells by host T lymphocytes
      requires the expression of cytokine-dependent molecules, such as class II major
      histocompatibility antigens, intracellular adhesion molecule 1 (ICAM-1), and
      lymphocyte function-associated antigen 3 (LFA-3). In the liver, activation of
      Kupffer cells after ischemic injury during the transplantation procedure may
      result in an early induction of cytokine-dependent molecules. METHODS: The
      pattern of induction of ICAM-1, HLA-DR, HLA-DQ, and LFA-3 was investigated in 30
      postreperfusion surgical biopsy specimens of liver allografts by an
      immunohistochemical technique. RESULTS: Two patterns of induction were observed:
      focal or diffuse. On hepatocytes, ICAM-1 was induced in 22 cases (11 focal, 11
      diffuse), HLA-DR in 18 cases (13 focal, 5 diffuse), HLA-DQ in 13 cases (3 focal,
      10 diffuse), and LFA-3 in 1 case (focal). On bile duct cells, HLA-DR was
      expressed in 19 cases, associated with HLA-DQ in 7 cases. No induction of ICAM-1
      and LFA-3 was detected. Compared with the other patients, the group of patients
      with diffuse postoperative hepatocellular induction of ICAM-1 was characterized
      by higher preharvesting serum transaminase levels in the donor (P < or = 0.001),
      suggestive of preoperative ischemic injury, and increased incidence of acute
      graft rejection (P = 0.04). CONCLUSIONS: Preoperative warm ischemia may modify
      the immunogenicity of liver allografts.

PMID- 7523219
TI  - Stimulation of in vivo pancreatic growth in the rat is mediated specifically by
      way of cholecystokinin-A receptors.
AB  - BACKGROUND/AIMS: Cholecystokinin (CCK) and gastrin stimulate growth of rodent
      pancreas in vivo. However, it remains unclear whether these growth effects are
      mediated specifically by CCK-A receptors, CCK-B receptors, or both. To clarify
      this issue, the present study examined the effect of highly selective and
      biologically active CCK agonists on pancreatic growth. METHODS: Rats were
      subcutaneously injected with either (1) CCK-8, a nonselective CCK agonist (2.50
      micrograms/kg body wt); (2) A-71623, a selective CCK-A agonist, tert-butyl
      oxycarbonyl-Trp-Lys (epsilon-N-2-methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe
      NH2 (1.84 micrograms/kg body wt); (3) SNF-8815; a selective CCK-B agonist,
      [(2R,3S)-beta-MePhe28, N-MeNle31]CCK26-33 (2.40 micrograms/kg body wt); or (4)
      saline (control) for 21 days. Rats were killed, and pancreatic weight, protein
      content, RNA content, DNA content, protein-DNA ratio, RNA-DNA ratio, pancreatic
      area per nucleus, and number of mitoses per 10,000 acinar cells were determined.
      RESULTS: Nonselective CCK agonist significantly increased pancreatic weight,
      protein, RNA, and DNA contents, and number of mitoses per 10,000 acinar cells.
      Likewise, selective CCK-A agonist significantly increased pancreatic weight,
      protein, RNA, and DNA contents, protein-DNA ratio, RNA-DNA ratio, pancreatic area
      per nucleus, and number of mitoses per 10,000 acinar cells. In contrast,
      selective and biologically active CCK-B agonist had no effect. CONCLUSION: These
      findings indicate that pancreatic growth is mediated specifically by CCK-A
      receptors in the rat in vivo.

PMID- 7523218
TI  - Effects of leukocyte and platelet depletion on ischemia--reperfusion injury to
      dog pancreas.
AB  - BACKGROUND/AIMS: Ischemia-reperfusion injury has been studied in various organs.
      Effects of leukocyte and platelet depletion on ischemia-reperfusion injury were
      evaluated using the isolated, perfused dog pancreas in vivo. METHODS: Pancreatic
      exocrine and endocrine functions were stimulated by an intra-arterial injection
      of cholecystokinin (10(-12) mol) and intravenous injection of glucose and
      arginine (1 g/kg body wt), respectively. The functions before and after 60
      minutes of ischemia were evaluated in the no treatment and in the leukocyte and
      platelet depletion groups. RESULTS: Cholecystokinin increased prostaglandin I2
      and thromboxane A2 production and stimulated exocrine pancreatic secretion.
      Glucose and arginine stimulated insulin and glucagon release from the pancreas.
      Sixty minutes of ischemia followed by 60 minutes of reperfusion damaged the
      pancreatic acinar and ductular cells. Ischemia of 60 minutes followed by 90
      minutes of reperfusion damaged beta cells. Removal of leukocytes (97.6%) and
      platelets (99.4%) by using a filter throughout the experiment prevented the
      ischemia-reperfusion injury, reduced plasma lipid peroxide and thromboxane A2,
      and increased prostaglandin I2 levels. CONCLUSIONS: Leukocytes and platelets seem
      to damage the pancreas during ischemia-reperfusion by increasing the peroxidation
      of structurally important cell membrane lipids and reduced the thromboxane A2
      prostaglandin I2 ratio, a predictor of cellular injury.

PMID- 7523221
TI  - Topical nitroglycerin for pain relief in acute esophagitis.

PMID- 7523222
TI  - Neural sites of the human colon colocalize nitric oxide synthase-related NADPH
      diaphorase activity and neuropeptide Y.
AB  - BACKGROUND/AIMS: Nitric oxide and neuropeptide Y (NPY) exert similar biological
      actions in the mammalian intestine including modulation of food intake, blood
      flow, motility, and secretion. In addition, these substances coexist in
      submucosal secretomotor neurons of the rodent intestine. The aim of this study
      was to determine the relative disposition of elements displaying NPY
      immunoreactivity and NO synthase-related nicotinamide adenine dinucleotide
      phosphate (NADPH) diaphorase activity in the nerve networks of the human infant
      colon. METHODS: Transverse and longitudinal sections, treated for
      immunohistofluorescent detection of NPY and then processed for NO synthase
      related NADPH diaphorase histochemistry, were examined. RESULTS: Neural elements
      containing NPY immunoreactivity and NO synthase-related activity were identified
      in the external muscle layers, myenteric plexus, and all nerve layers of the
      submucosa, including Henle's plexus, the intermediate nerve layer, and Meissner's
      plexus. Perivascular NPY-immunoreactive nerve fibers did not contain NO synthase
      activity. There were no nitrergic perivascular nerve fibers. NPY-immunoreactive
      endocrine cells in the mucosa did not display NO synthase-related activity.
      CONCLUSIONS: These findings provide anatomical data indicating that NPY
      immunoreactivity and NO synthase-related activity are extensively colocalized in
      all layers of the human infant gut wall.

PMID- 7523220
TI  - Nitric oxide: regulator of P-selectin expression.

PMID- 7523223
TI  - Role of histamine receptors in intestinal repair after ischemia-reperfusion in
      rats.
AB  - BACKGROUND/AIMS: Previously, we showed that an elevated production of histamine
      promotes the healing of injured intestinal mucosa after ischemia-reperfusion. The
      aim of the present study was to determine whether histamine-mediated repair of
      the intestinal mucosa after ischemia-reperfusion involves the engagement of H1 or
      H2 receptors. METHODS: The superior mesenteric artery was occluded for 15 minutes
      followed by reperfusion, and H1- or H2-receptor antagonists were infused
      intraduodenally. After ischemia-reperfusion, ornithine decarboxylase activity in
      the jejunal mucosa and lipid transport to mesenteric lymph were examined.
      RESULTS: In jejunal mucosa, ornithine decarboxylase activity markedly increased
      at 6 hours after reperfusion and remained elevated at 48 hours. The ischemia
      reperfusion-induced increase in ornithine decarboxylase activity was attenuated
      (in a dose-dependent manner) by an H1-receptor antagonist (chlorpheniramine
      maleate) but not by an H2 antagonist (cimetidine). Intraperitoneal injection of
      an H3 antagonist (thioperamide) increased histamine output in mesenteric lymph
      and stimulated intestinal ornithine decarboxylase activity. Transport of dietary
      lipid into mesenteric lymph was depressed 24 hours after an ischemic insult, yet
      it returned to the normal level 48 hours after ischemia-reperfusion. The recovery
      of the lipid transport normally observed at 48 hours after ischemia-reperfusion
      was attenuated by the H1 antagonist. CONCLUSIONS: The beneficial effects of
      histamine on the repair of intestinal mucosa after ischemia-reperfusion results
      from the engagement and activation of the H1 receptor.

PMID- 7523224
TI  - Crohn's disease, ulcerative colitis, and normal intestinal lymphocytes express
      integrins in dissimilar patterns.
AB  - BACKGROUND/AIMS: The integrin family of adhesion molecules on intestinal lamina
      propria mononuclear cells (LPMNC) was studied using fluorescence-activated cell
      cytometry. These molecules are implicated in extravascular cell migration and are
      important regulators of disease. METHODS: Using fluorescence-activated cell
      cytometry, B- and T-cell subsets in the intestines of 10 normal patients, 11
      patients with Crohn's disease, and 8 patients with ulcerative colitis were
      stained with monoclonal antibodies to a panel of integrins. RESULTS: Expression
      of alpha integrins on CD3+ T cells and CD19+ B cells was different in normal and
      inflammatory bowel disease LPMNC. Ulcerative colitis T cells expressed less beta
      1 and alpha 4 and significantly more alpha 2 and alpha 6. There was a difference
      in alpha 4 and beta 1 expression between LPMNC B cells from Crohn's disease and
      normal intestines. Sixteen percent of CD19+ LPMNC B cells from Crohn's and 19% of
      ulcerative colitis LPMNC expressed alpha 2. Crohn's and ulcerative colitis CD19+
      LPMNC B cells expressed more alpha 5 integrin than normal specimens. CD3+ T cells
      and CD19+ B cells expressed alpha 6 only in ulcerative colitis. Ulcerative
      colitis and Crohn's disease CD19+ LPMNC expressed less alpha 4, consistent with
      their reciprocal increases of alpha 5 and alpha 2. A difference in beta 7
      (Peyer's patch specific) antigen was observed between inflammatory bowel disease
      and normal LPMNC for both CD3+ and CD19+ LPMNC. CONCLUSIONS: These findings
      identify the differences of lymphocyte homing capability in inflammatory bowel
      disease and normal intestine.

PMID- 7523225
TI  - A conserved epitope on H+,K(+)-adenosine triphosphatase of parietal cells
      discerned by a murine gastritogenic T-cell clone.
AB  - BACKGROUND/AIMS: H+,K(+)-adenosine triphosphatase (H+,K(+)-ATPase) of parietal
      cells is an organ-specific enzyme recognized by autoantibodies found in human and
      murine autoimmune gastritis (AIG). Murine AIG can be induced in BALB/c mice by
      thymectomy 3 days after birth and is a T cell-mediated disease. This study
      examined the specificity of T cells that cause AIG and the role of H+,K(+)-ATPase
      in this disease. METHODS: From an AIG mouse, a gastritogenic T-cell clone (II-6)
      was established, and its reactivity to synthetic peptides of H+,K(+)-ATPase was
      tested. RESULTS: II-6 cells are CD4+, V beta 14+, and interferon gamma producers.
      Adoptive transfer of II-6 cells to syngeneic nude mice resulted in AIG without
      the production of autoantibodies to parietal cells. The II-6 cells were
      responsive not only to murine but also to human and porcine parietal cells. Their
      proliferation was also induced by amino acids 891-905 (alpha 891) and 892-906
      (alpha 892) of the alpha subunit of porcine and human H+,K(+)-ATPase,
      respectively. CONCLUSIONS: The T-cell response to a single epitope of H+,K(+)
      ATPase, the amino acid sequence of which is conserved among at least three
      mammals tested, is sufficient to cause AIG. Autoantibodies to parietal cells are
      not detected in these AIG mice.

PMID- 7523227
TI  - In vitro secretion of anti-GOR protein and anti-hepatitis C virus antibodies in
      patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: Anti-GOR antibodies may reflect hepatitis C virus (HCV)--related
      autoimmunity or cross-reactivity with HCV core antigen. This study aimed to
      evaluate the clinical significance of anti-GOR antibodies. METHODS: Peripheral
      blood mononuclear cells (PBMCs) were isolated from 35 patients with HCV and 48
      controls and cultured for 8 days. The in vitro antibody secretion by PBMC was
      determined using specific enzyme-linked immunosorbent assays and recombinant
      immunoblot assay. RESULTS: In 22 of 35 patients with HCV (62.9%), PBMCs secreted
      anti-c22-3 or anti-c33c antibodies. However, in 3 of 48 controls (6.2%), PBMCs
      secreted anti-c33c antibodies alone. A significant in vitro anti-GOR response was
      found in 13 of 35 patients (37.1%) with HCV in relation to 4 of 48 controls
      (8.3%). In 12 of these patients (92.3%), anti-GOR were found in vitro and in
      serum. Two patients with HCV produced in vitro anti-GOR but not anti-c22-3
      antibodies. Regarding disease activity, in vitro anti-GOR-positive patients with
      HCV had significantly higher alanine aminotransferase levels (108.8 +/- 17.8 U/L
      vs. 64.5 +/- 7.6 U/L; P < 0.01) and more frequent signs of chronic active
      hepatitis (10 of 13 [76.9%] vs. 10 of 22 [45.5%]) than patients with HCV without
      in vitro anti-GOR response. CONCLUSIONS: The humoral anti-GOR response in vitro
      is closely related to HCV infection and disease activity. Anti-GOR and anti-HCV
      core antibodies are regulated independently. It is likely that anti-GOR may
      reflect an HCV-associated autoimmune phenomenon.

PMID- 7523228
TI  - Expression of cytokine-dependent immune adhesion molecules by hepatocytes and
      bile duct cells in chronic hepatitis C.
AB  - BACKGROUND/AIMS: The pathogenesis of liver cell injury in chronic hepatitis C is
      poorly understood. To test whether immune-mediated mechanisms might be involved
      in the pathogenesis of liver cell injury during infection by hepatitis C virus,
      the expression of cytokine-dependent immune molecules by hepatocytes and bile
      duct cells during chronic hepatitis C was studied. METHODS: In 35 patients,
      expression of class I and II HLA antigens, intercellular adhesion molecule (ICAM)
      1, and lymphocyte function antigen (LFA) 3 was studied by immunohistochemistry
      and scored by a semiquantitative grading system. Statistical analysis was
      performed using Spearman's test and t test. RESULTS: Class I HLA antigens were
      induced on hepatocytes in 20 cases. In all cases, HLA-DR, ICAM-1, and/or LFA-3
      were detected on hepatocytes in piecemeal necrosis and intralobular clusters.
      Bile duct cells expressed HLA-DR in 32 cases and ICAM-1 and LFA-3 in 14 cases.
      Expression levels of immune molecules on hepatocytes correlated with
      aminotransferase activity (P < 0.035), histological activity (P < 0.001), and
      score of necrosis (P < 0.01). ICAM-1 expression on hepatocytes was higher in
      patients with intraportal lymphoid nodules (P = 0.005). Expression levels of ICAM
      1 and LFA-3 on bile ducts correlated with the severity of bile duct damage (P <
      0.015). CONCLUSIONS: These results suggest the involvement of immune-mediated
      mechanisms in the pathogenesis of liver cell injury in chronic hepatitis C.

PMID- 7523226
TI  - Cellular and humoral immune reactions against autoantigens and hepatitis C viral
      antigens in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Previous reports have suggested that the hepatitis C virus (HCV)
      may induce autoimmune hepatitis. The aim of this study was to examine this
      hypothesis by investigating humoral and cellular immune responses to HCV-related
      antigens and various autoantigens in patients with chronic HCV infections.
      METHODS: Lymphoproliferative responses in vitro and/or circulating antibodies to
      an HCV core peptide, the putative autoantigen GOR, the liver-specific hepatic
      asialoglycoprotein receptor (ASGP-R), and other autoantigens were investigated in
      27 adults with chronic hepatitis C. RESULTS: Five patients with HCV (18.5%)
      showed cellular immune responses to ASGP-R and two others had antibodies to ASGP
      R, whereas 6 of 14 patients (42.8%) showed cellular responses to GOR and 7 of 14
      patients (50%) showed responses to HCV core. Other autoantibodies were detected
      in three patients (11%). Nine patients with autoimmune hepatitis studied
      concurrently for comparison showed cellular and/or humoral responses to ASGP-R
      but not to GOR. Only 2 of 11 patients with other chronic liver disorders showed
      immune responses to any antigen tested. CONCLUSIONS: Specific immunocompetence
      against HCV-related antigens can often be shown in patients with chronic
      hepatitis C but is infrequently accompanied by autoreactions against liver
      specific or nonspecific antigens. A reported association between T-cell responses
      to HCV core and lack of liver damage could not be confirmed.

PMID- 7523229
TI  - Hepatitis C virus and autoimmunity: fortuitous association or reality?

PMID- 7523230
TI  - c-src tyrosine kinase activity: a marker of dysplasia in ulcerative colitis.

PMID- 7523231
TI  - Does performance status influence the outcome of Nd:YAG laser therapy of proximal
      esophageal tumors?
AB  - The value of endoscopic palliative therapy for malignant obstruction in the
      proximal esophagus has been questioned. To assess the importance of pre-treatment
      performance status on treatment outcome, we reviewed the records of patients with
      tumors of the proximal esophagus undergoing endoscopic laser therapy between
      January 1986 and December 1988. As compared with 10 patients having a good
      performance status, eight patients with a poor performance status had a lower
      frequency of obtaining complete functional relief of dysphagia (14% versus 71%),
      an increased rate of complications (50% versus 0%), and a shorter median survival
      time (24 days versus 161 days). We conclude that performance status should be
      considered in determining the appropriateness of laser therapy in patients with
      proximal esophageal cancer.

PMID- 7523232
TI  - Endoscopic stent placement for cancer of the lower esophagus and gastric cardia.
AB  - We reviewed our results of using stents for palliation of cancer of the lower
      third of the esophagus and gastric cardia. During a 14-year period, 76 patients
      with either lower third esophageal cancer (n = 43) or cancer of the gastric
      cardia (n = 33) received stents for palliation of malignant dysphagia. Successful
      endoscopic placement was initially achieved in all patients, with 71 patients
      available for follow-up. Of these, 40 (56%) were subsequently able to eat solid
      or semi-solid food, 25 (35%) could swallow only liquids, and 6 (8%) were
      unimproved. The combined early and late complication rate totalled 22%. Early
      complications included perforation (n = 3) and stent migration (n = 4); late
      complications consisted of dislodgment (n = 6), obstruction by tumor (n = 2), and
      severe esophagitis (n = 1). There were no procedure-related deaths, but survival
      at 1 year was estimated to be only 1.5%, with a median survival of 2.5 months
      after stent insertion. The endoscopic placement of prosthetic stents for cancer
      of the distal esophagus and gastric cardia entails a higher complication rate,
      less successful palliation, and shorter survival time compared to similar
      treatment for more proximal esophageal cancer.

PMID- 7523234
TI  - Sterility of india ink.

PMID- 7523233
TI  - Management of a tracheoesophageal fistula with a silicone-covered self-expanding
      metal stent.

PMID- 7523235
TI  - Comparative effects of the dihydropyridine-type calcium-agonists (-)-S-Bay K
      8644, (+/-)-Bay-W 5035 and (+/-)-Bay-T 5006 on human platelet aggregability.
AB  - 1. Human platelet aggregation induced by collagen is concentration-dependently
      inhibited by dihydropyridine (DHP)-type calcium(Ca)-agonists. 2. There was no
      significant difference between the maximal anti-aggregatory effects or the anti
      aggregatory potencies of (-)-S-Bay-K 8644 (EC50: 5.3 +/- 1.5 x 10(-5) M), (+/-)
      Bay-W 5035 (EC50: 14.9 +/- 8.8 x 10(-5) M) or (+/-)-Bay-T 5006 (EC50: 2.7 +/- 1.9
      x 10(-5) M) (P > 0.05). 3. Antiaggregatory effects of DHP-type Ca-agonists seem
      to be independent of Ca-channel activation.

PMID- 7523236
TI  - Actions of abscisic acid and the analogue SD217595 on calcium mediated activity
      of rat vas deferens smooth muscle.
AB  - 1. K(+)-induced and Ca(2+)-induced contractures of rat prostatic and epididymal
      vas deferens smooth muscle were used to screen ABA and its analogue SD217595 for
      Ca2+ modulatory activity. 2. The Ca2+ agonist BAY K8644 significantly enhanced
      Ca(2+)-induced contractures while the Ca2+ entry blocker nifedipine strongly
      inhibited such contractures in both types of vas deferens preparation over the
      whole Ca2+ concentration range employed. 3. At 10(-7) mol 1(-1) ABA had no
      significant effect on K(+)-induced or Ca(2+)-induced contractures nor did it
      change the phasic/tonic force ratio in the preparations. 4. The ABA analogue
      SD217595 strongly inhibited Ca(2+)-induced contractures over the whole Ca2+
      concentration range employed in both prostatic and epididymal vas deferens. 5. It
      is concluded that ABA is without significant Ca2+ modulatory activity in this
      smooth muscle preparation but the ABA analogue SD217595 possesses strong Ca2+
      entry blocking ability.

PMID- 7523238
TI  - Mepacrine inhibits amylase secretion mediated by a guanylnucleotide binding
      protein.
AB  - 1. In intact rat pancreatic acini, 10 nM bombesin, 100 nM phorbol ester TPA and
      10 mM fluoroaluminate increased amylase secretion 5-, 3- and 4-fold respectively.
      2. Mepacrine dose-dependently inhibited the response to bombesin and
      fluoroaluminate but did not affect the response to TPA. 3. In permeabilized
      acini, mepacrine inhibited the secretory response to GTP gamma S without
      modifying the response to TPA.

PMID- 7523237
TI  - Pharmacological effects of recombinant human granulocyte colony-stimulating
      factor modified by polyethylene glycol on anticancer drug-induced neutropenia in
      mice.
AB  - 1. To clarify the pharmacological effects of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) conjugated to polyethylene glycol (PEG), its effects
      on the number of circulating neutrophils in mice made neutropenic by
      cyclophosphamide (CPA) or 5-fluorouracil (5-FU) were compared with rhG-CSF
      lacking PEG. 2. In normal mice, PEG-conjugated rhG-CSF (PEG-rhG-CSF, 10
      micrograms protein/kg) induced an increase in neutrophils which lasted for 72 h
      after injection whereas the effect of rhG-CSF (10 micrograms protein/kg)
      disappeared by 24 h after injection. 3. In CPA or 5-FU-induced neutropenic mice,
      PEG-rhG-CSF inhibited neutropenia or accelerated recovery from neutropenia and
      its potency was higher than that of rhG-CSF. 4. These results indicate that PEG
      rhG-CSF has a longer duration of action than rhG-CSF and is more effective in the
      recovery from neutropenia.

PMID- 7523240
TI  - Rodent insulin receptors are immunologically different from other mammalian
      insulin receptors.
AB  - Four monoclonal antibodies (MA-5, MA-10, MA-20, and MA-51) and one polyclonal
      antibody (ARS-2) against human insulin receptor were used to immunoprecipitate
      the insulin receptor from several species which had been photolabeled with N
      epsilon B29-monoazido-benzoyl-[125I]iodoinsulin. All four monoclonal antibodies
      immunoprecipitated human insulin receptor from human placental membranes. MA-10
      and MA-51, but not MA-5 or MA-20, immunoprecipitated insulin receptors from liver
      plasma membranes of rabbit, guinea pig, dog, cattle, pig, and chicken. None of
      the monoclonal antibodies immunoprecipitated insulin receptors of rat, mouse,
      hamster, or chinchilla. In contrast, all of the insulin receptors were
      immunoprecipitated by the polyclonal anti-insulin receptor antibody, ARS-2. MA-10
      and MA-51 compared with [125I]iodoinsulin for binding to guinea pig and rabbit
      liver plasma membranes in a fashion similar to insulin, although less
      effectively. MA-51 also mimicked the action of insulin by stimulating lipogenesis
      and autophosphorylation of the insulin receptor beta subunit in isolated rabbit
      adipocytes. The results suggest that insulin receptors of mammals, other than
      rodent, share with human insulin receptor the same epitope(s) recognized by MA-10
      and MA-51. Rodent insulin receptors, with the exception of guinea pig, are
      different. We speculate that the difference lies in the amino acid sequence 485
      599 of the alpha subunit of the insulin receptor.

PMID- 7523239
TI  - Development of maturational competence of oocytes of red seabream, Pagrus major,
      after human chorionic gonadotropin treatment in vitro requires RNA and protein
      synthesis.
AB  - The effects of human chorionic gonadotropin (HCG) and 17 alpha,20 beta-dihydroxy
      4-pregnen-3-one (DHP) on in vitro germinal vesicle breakdown (GVBD) in oocytes
      obtained at different times of day from a daily spawning marine teleost, the red
      seabream Pagrus major, were investigated. Oocytes isolated at 0800 hr underwent
      GVBD in response to HCG (10 IU/ml) but not to DHP (10 ng/ml). GVBD could be
      induced in oocytes isolated at 1600 hr by either HCG or DHP. Oocytes underwent
      GVBD in response to DHP after DHP-insensitive oocytes were incubated with HCG for
      30, 60, or 120 min. The effects of actinomycin D (a transcriptional inhibitor)
      and cycloheximide (a translational inhibitor) on HCG- and DHP-induced GVBD were
      also investigated. Actinomycin D (1 microgram/ml) totally inhibited HCG-induction
      of GVBD in oocytes isolated at 0600 and 0800 hr. Actinomycin D also significantly
      inhibited GVBD induced by HCG in combination with DHP in oocytes taken at 0600
      and 0800 hr. Cycloheximide (1 microgram/ml) completely inhibited the inducation
      of GVBD by HCG or DHP, alone or in combination, in oocytes obtained at 0600,
      1000, and 1400 hr. These results indicate that gonadotropin induces maturational
      competence (responsiveness to maturation-inducing steroid) in oocytes of red
      seabream. These results also suggest that gonadotropin-induced synthesis of new
      protein through a mechanism dependent on RNA is essential for the development of
      maturational competence in oocytes of red seabream.

PMID- 7523242
TI  - Immunosuppressive agents in chronic severe asthma.
AB  - Previous immunosuppressive agents utilized as therapies for immune system
      mediated diseases such as chronic allergic asthma, and rheumatoid arthritis
      include purine antagonists, methotrexate, and gold salts. These treatment
      modalities have been shown to elicit either limited treatment efficacy or to
      produce undesirable side effects in many individuals. Cyclosporin A is a potent
      immunosuppressive agent which appears to arrest division of T lymphocytes and
      inhibit mediator release from mast cells. However, like other immunosuppressive
      agents, cyclosporin A may also produce many potentially serious side effects;
      among these is the possibility of irreversible renal damage. Nephrotoxicity can
      be attenuated, because renal pathological changes seem to be high cumulative dose
      related. If whole blood levels of cyclosporin A are maintained between 200 and
      500 ng/mL, serious renal toxicity is unusual. Investigation of cyclosporin A in
      individuals who have severe long-term corticosteroid-dependent chronic asthma has
      demonstrated the efficacy of this agent, resulting in clinically significant
      improvement in pulmonary function. Therefore, it can be hypothesized that T
      lymphocytes may act as effector cells in cell-mediated hypersensitivity reactions
      in atopic allergic inflammation.

PMID- 7523241
TI  - Vibrio vulnificus may produce a metalloprotease causing an edematous skin lesion
      in vivo.
AB  - Vibrio vulnificus, an opportunistic human pathogen, secretes a metalloprotease
      which has been suspected of being the causative factor for edematous skin
      lesions. The antibody against alpha-macroglobulin, the sole plasma inactivator of
      V. vulnificus metalloprotease, delayed clearance of the protease administered
      into dorsal skin, and increased the edema-forming ability of living bacterial
      cells. The derivative of the protease, which is resistant to the inactivating
      action of alpha-macroglobulin, was not excluded from the dorsal skin.
      Furthermore, the vibrio inoculated into the mammalian serum was found to produce
      the protease in adequate amounts. These results suggest that V. vulnificus
      secretes a metalloprotease into the interstitial-tissue space, resulting in the
      development of an edematous skin lesion, and that the protease is immediately
      inactivated by alpha-macroglobulin and subsequently excluded.

PMID- 7523243
TI  - Functional reconstitution of wild-type and mutant Tetrahymena telomerase.
AB  - Telomerase is a ribonucleoprotein that catalyzes telomere elongation in vitro and
      in vivo. The 159-nucleotide RNA component of Tetrahymena telomerase contains the
      sequence 5'-CAACCCCAA-3' ("template region"), which serves as a template for the
      addition of the sequence d(TTGGGG)n to Tetrahymena telomeres. To dissect the
      Tetrahymena telomerase enzyme mechanism, we developed a functional in vitro
      reconstitution assay. After removal of the essential telomerase RNA by
      micrococcal nuclease digestion of partially purified telomerase, the addition of
      in vitro-transcribed telomerase RNA reconstituted telomerase activity. The
      reconstituted activity was processive and showed the same primer specificities as
      native telomerase. Mutants in the RNA template region were tested in
      reconstitution assays to determine the role of the residues in this region in
      primer recognition and elongation. Two template mutants, encoding the sequences
      5'-UAACCCCAA-3' and 5'-UAACCCUAA-3', specified the incorporation of dATP into the
      sequence d(TTAGGG). Telomerase reconstituted with a template mutant encoding the
      sequence 5'-CAACCCUAA-3' did not specify dATP incorporation and elongation by
      this mutant was not terminated by the addition of ddATP. In addition, a template
      mutant encoding the sequence 5'-CGGCCCCAA-3' specified the incorporation of ddCTP
      but not ddTTP while a mutant encoding the sequence 5'-CAACCCCGG-3' specified the
      incorporation of ddTTP but not ddCTP. These data suggest that only the most 5'
      six residues of the template region dictate the addition of telomeric repeats.

PMID- 7523244
TI  - The Drosophila orb RNA-binding protein is required for the formation of the egg
      chamber and establishment of polarity.
AB  - The orb gene of Drosophila encodes sex-specific germ-line proteins that contain
      two RRM-type RNA-binding domains. Here we report the distribution of Orb protein
      in wild-type, tumorous, and orb mutant ovaries. The wild-type distribution of Orb
      protein during oogenesis resembles that of its RNA, preferentially accumulating
      in the cytoplasm of the developing oocyte shortly after the formation of the 16
      cell cyst. As anticipated from its germ-line expression, mutations in orb lead to
      female sterility. Analysis of the effect of orb mutants on the distribution of
      RNAs known to be required for oocyte differentiation and polarity suggests that
      orb functions in RNA localization at multiple points during oogenesis. In
      addition, phenotypic characterization of the orb mutants indicates that the gene
      is required early in oogenesis for formation of the 16-cell cyst. It then
      functions in the differentiation of the oocyte and is required for the three
      dimensional reorganization of the germ cells in the cyst as well as for the
      establishment of normal germ-line-soma interactions in the egg chamber.

PMID- 7523245
TI  - Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD
      protein (p300) reveals a protein with properties of a transcriptional adaptor.
AB  - The growth-controlling functions of the adenovirus E1A oncoprotein depend on its
      ability ot interact with a set of cellular proteins. Among these are the
      retinoblastoma protein, p107, p130, and p300. We have isolated a cDNA encoding
      full-length human p300 and mapped the chromosomal location of the gene to
      chromosome 22q13. p300 contains three cysteine- and histidine-rich regions of
      which the most carboxy-terminal region interacts specifically with E1A. In its
      center, p300 contains a bromodomain, a hallmark of certain transcriptional
      coactivators. We have examined the ability of p300 to overcome the repressive
      effect of E1A on the SV40 enhancer. We show that p300 molecules lacking an intact
      E1A-binding site can bypass E1A repression and restore to a significant extent
      the activity of the SV40 enhancer, even in the presence of high levels of E1A
      protein. These results imply that p300 may function as a transcriptional adaptor
      protein for certain complex transcriptional regulatory elements.

PMID- 7523246
TI  - Expression efficiency of the human thrombomodulin-encoding gene in various vector
      and host systems.
AB  - Expression systems were developed for evaluating recombinant human thrombomodulin
      (TM) production in different host cell lines by investigating the performance of
      five mammalian expression vectors. The expression vectors were constructed so
      that they contain multiple monocistronic gene cassettes which include a gene
      encoding a dominant selectable marker, HyR (hygromycin B phosphotransferase),
      under the regulation of the thymidine kinase promoter, the target gene which
      encodes a truncated human re-TM under the regulation of various promoters, an
      amplifiable gene (Dhfr) encoding murine dihydrofolate reductase under the
      regulation of either the SV40 early or late promoter along with the SV40 enhancer
      and the SV40 ori. We tested the performance of the five expression vectors in
      human embryonic kidney cells (HEK293), baby hamster kidney cells (BHK), human
      melanoma cells (CHL-1) and Dhfr- Chinese hamster ovary cells (CHO/Dhfr-). We
      found that the efficiency of DNA uptake, transient expression and stable
      expression of the different expression vectors were all cell-line dependent.
      However, the myeloproliferative sarcoma virus (MPSV) LTR promoter consistently
      showed higher expression levels in all cell lines, particularly in HEK293 cells.
      These results were confirmed by the distribution curves of the level of
      expression of individual clones. Furthermore, by amplifying Dhfr in transfected
      CHO/Dhfr- cells with 100 nM methotrexate, we achieved a 20-fold increase in re-TM
      production using the SV40 late promoter to control murine Dhfr expression. Our
      data from DNA and mRNA analysis reveal that pMPSV-TM has a high transcription
      efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523247
TI  - Sequence of a cDNA clone encoding the Atlantic salmon alpha 1
      microglobulin/bikunin protein.
AB  - We report here the nucleotide sequence of a cDNA clone encoding the salmon (Salmo
      salar) alpha 1-microglobulin/bikunin precursor protein (sAMBP). The encoded
      precursor shows 36 and 42% amino acid (aa) similarity to the AMBP of pig and
      human, respectively. Signature aa motifs are conserved. The data infer that the
      ancestral AMBP gene arose more than 450 million years ago, before the tetrapod
      fish divergence.

PMID- 7523248
TI  - DNA polymerase fluorescent substrates with reversible 3'-tags.
AB  - We have synthesized 3'-substituted-2'-deoxyribonucleotide-5'-triphosphates
      corresponding to A, T, G and C. The 3' position was esterified by a separate
      anthranylic derivative (3'-tag) giving specific fluorescent properties to each
      nucleotide (nt). These nt acted as substrates with several DNA polymerases
      leading to chain termination. Upon alkali or enzymatic treatment of the
      terminated DNA chain, free 3'-hydroxyl groups were recovered and found able to
      undergo chain extension when incubated with a mixture of dNTPs and a DNA
      polymerase. Because each tag has different fluorescent properties in itself,
      i.e., as a free acid, it theoretically is possible, after removal and
      characterization of the tag, to infer which nt has been inserted. Reiteration of
      the process can then be used to determine a nt sequence with a non-gel-based
      method amenable to automation.

PMID- 7523249
TI  - Characterization and sequence analysis of a Streptomyces rochei A2 endoglucanase
      encoding gene.
AB  - A 7-kb fragment of Streptomyces rochei A2 chromosomal DNA was cloned into pAT153
      and shown to confer endoglucanase (EglS) activity on Escherichia coli cells. In
      E. coli clones, the EglS was secreted into the periplasm. Deletion analysis
      revealed that an 827-bp fragment was enough for the enzymatic activity. Sequence
      analysis showed that the 827-bp fragment codes for the catalytic domain of the
      enzyme. The complete sequence of the gene (eglS) is 1149-bp long. A signal
      peptide, a catalytic domain and a cellulose-binding domain were identified from
      the nucleotide sequence, and the EglS found to belong to the family H of
      cellulase catalytic domains. These conclusions were substantiated by
      determination of the N-terminal sequence of the purified protein and zymogram
      analysis, which revealed protein species with a molecular mass equal to that
      deduced from the nt sequence analysis.

PMID- 7523251
TI  - Isolation of maltose-regulated genes from the hyperthermophilic archaeum,
      Pyrococcus furiosus, by subtractive hybridization.
AB  - The hyperthermophilic archaeum, Pyrococcus furiosus, utilizes maltose as a
      preferred carbon source for growth. 32P-labeled complementary DNA (cDNA) probes
      representing maltose-regulated genes were obtained by a subtractive hybridization
      procedure that minimized retrieval of ribosomal RNA (rRNA) sequences during
      screening. Genomic DNA clones were isolated by positive hybridization to these
      probes. Genes whose expression varied both in the level of transcription,
      relative to rRNA, as well as in the degree of regulation were obtained; the
      extent of regulation varied over a wide range, from as little as fivefold to as
      high as 50-100-fold. DNA sequence analysis of several of these regulated genes
      indicated that the subtraction library included gene products required for
      maltose utilization (e.g., pyruvate dikinase), as well as growth-rate-related
      genes such as those encoding ribosomal proteins and RNA polymerase subunits. Our
      approach is applicable to studying gene regulation in organisms that are not
      amenable to classical genetic techniques.

PMID- 7523250
TI  - In vivo transcripts of the S-layer-encoding structural gene of the archaeon
      Methanococcus voltae.
AB  - The 5' region of the S-layer-encoding structural gene (sla) of Methanococcus
      voltae was sequenced. The sequence information was then used to identify the in
      vivo transcription products of the gene. We observed three transcripts, and
      upstream from each transcription start point was a region with similarity to the
      Box A consensus sequence observed in archaeal promoters. In two of the three
      cases, two Box A sequences were present in tandem. This arrangement may play a
      role in the high level of gene expression expected for the sla gene. Presumptive
      archaeal Box B signatures were also identified.

PMID- 7523254
TI  - Identification of a Vibrio cholerae ToxR-activated gene (tagD) that is physically
      linked to the toxin-coregulated pilus (tcp) gene cluster.
AB  - The toxin-coregulated pilus (TCP)-encoding gene cluster (tcp) specifies a type-IV
      pilus that is a major colonization determinant of Vibrio cholerae. We have
      identified a gene 200 bp upstream from the tcp cluster that requires ToxR for
      expression. We have designated this gene tagD (ToxR-activated gene) and have
      shown that tagD is encoded on a 600-nt transcript. The deduced tagD product is a
      164-amino-acid polypeptide (20 kDa). Interestingly, TagD shares a high degree of
      similarity to a protein of Streptococcus sanguis 12 that is thought to play a
      role in fimbriae synthesis or assembly. The high degree of similarity between
      tagD and the Ss 12 protein provides preliminary evidence that tagD represents an
      additional member of the tcp cluster.

PMID- 7523252
TI  - Permissible peptide insertions surrounding the signal peptide-mature protein
      junction of the ClpG prepilin: CS31A fimbriae of Escherichia coli as carriers of
      foreign sequences.
AB  - The clpG gene, expressing the Escherichia coli major CS31A fimbrial subunit ClpG,
      was subjected to random mutagenesis by insertion of an EcoRI linker and a
      kanamycin-resistance (KmR) cassette into the multiple newly generated EcoRI
      sites. The KmR gene was then excised by PstI, which left a 48-bp linker
      representing the heterologous sequence. The same procedure was followed to
      introduce a synthetic oligodeoxyribonucleotide (oligo) corresponding to epitope C
      from the spike protein S from the porcine transmissible gastroenteritis
      coronavirus (TGEV). Nine insertion/deletion mutants (indels) that contained long
      foreign peptides variously located around the ClpG signal peptide (SP) processing
      site were characterized. A striking feature of this study is the variety of amino
      acid (aa) insertions in the ClpG prepilin that have little or no effect on CS31A
      fimbria biogenesis. These 'permissive' sites tolerate inserts of 18 or 19 aa and
      accept sequences of different natures in view of their aa composition, charge and
      hydrophobicity. The results obtained here are also interesting in light of the
      high level of aa sequence conservation seen in the SP and N-terminal domains of
      the ClpG-related subunits. The structure-function relationship of the ClpG SP is
      discussed. The TGEV-C epitope fused to the N-terminal end of the mature ClpG
      protein was cell-surface exposed, as observed on immuno-electron microscopy.
      Therefore, the CS31A fimbria seems to be a potent tool for the presentation of
      foreign antigenic determinants or the production of heterologous polypeptides in
      E. coli.

PMID- 7523255
TI  - Impairment of cytoskeletal protein transport due to aging or beta,beta'
      iminodipropionitrile intoxication in the rat sciatic nerve.
AB  - Three major age-related changes in cytoskeletal organization and metabolism in
      the axon were observed by comparing slow axonal transport in the sciatic nerves
      of rats aged 7-80 weeks: (a) a progressive decrease in the rate of slow axonal
      transport, (b) a tight association of cold-insoluble tubulin with the
      neurofilament (NF) proteins and (c) an accelerated proteolysis of the severely
      retarded proteins, especially NF proteins. These changes were reproduced to a
      large extent in the young animal by intoxication with beta,beta'
      iminodipropionitrile (IDPN). As IDPN is known to impair the axonal transport of
      NF proteins and cause segregation of NFs from microtubules, the results indicate
      that NF-microtubule interaction is one of the major factors regulating the axonal
      cytoskeleton. The importance of the balance between transport rate and
      degradation rate in the maintenance of the normal axonal cytoskeleton is stressed
      especially in the aged animal.

PMID- 7523256
TI  - Anterior chamber angle vascularization in Sturge-Weber syndrome. Report of a
      case.
AB  - The case of a 20-year-old woman with a left-sided facial hemangioma and a
      homolateral glaucoma is reported, complete with the histology of a trabeculectomy
      specimen. Her left eye had an episcleral hemangioma and goniodysgenetic features
      in the anterior chamber angle, while the intraocular pressure was measured to be
      45 mmHg. The left optic disc showed a large cupping and the left visual field was
      constricted. The right eye had no glaucomatous changes. Histological examination
      of the trabeculectomy specimen by both light and electron microscopy showed
      multiple congenital anomalies. There was a cluster of blood vessels in the
      trabecular meshwork. Abnormal accumulations of fine granular extracellular
      matrixes were observed in both the juxtacanalicular connective tissue and around
      the vascular structures. The lumen of Schlemm's canal was subdivided into three
      or four parts with few giant vacuole structures. The endothelial cells lining the
      inner wall of Schlemm's canal contained a well-formed basal lamina with many
      villi projecting into the lumen. These findings suggest that the multiple
      anomalies observed in the trabecular tissue may contribute to the manifestation
      of glaucoma in Sturge-Weber syndrome.

PMID- 7523253
TI  - Identification of a ToxR-activated gene, tagE, that lies within the accessory
      colonization factor gene cluster of Vibrio cholerae O395.
AB  - The nucleotide (nt) sequence has been determined for a Vibrio cholerae ToxR
      activated gene designated tagE that is located within a cluster of genes required
      for efficient intestinal colonization. The tagE gene encompasses 909 nt and is
      predicted to encode a 303-amino-acid (aa) protein with an estimated molecular
      mass of 34,468 Da. Computer-assisted similarity searches revealed that TagE
      possesses aa sequence similarity with Escherichia coli OrfU and Staphylococcus
      simulans lysostaphin, two proteins that are involved in cell-wall biosynthesis
      and peptidoglycan degradation, respectively. The role, if any, that TagE plays in
      the accessory colonization factor phenotype is currently under investigation.

PMID- 7523257
TI  - Clinical application of digital indocyanine green videoangiography in senile
      macular degeneration.
AB  - Digital indocyanine green videoangiography (ICGV) was done in 34 eyes of 24
      patients with aging macular degeneration (AMD), including drusen, either alone (6
      eyes) or in association with other AMD changes (9 eyes), geographic atrophy of
      the retinal pigment epithelium (2 eyes), well-defined choroidal
      neovascularization (CNV; 3 eyes), occult CNV (12 eyes) and recurrent CNV (11
      eyes). Of the 11 eyes with soft drusen, 10 showed abnormal fluorescence in the
      late ICGV picture. ICGV of the 4 eyes with hard drusen showed no abnormality. The
      geographic atrophy of the retinal pigment epithelium and choriocapillaris
      remained hypofluorescent with sharply demarcated boundaries throughout the study.
      ICGV confirmed the presence of CNV in all 3 eyes with well-defined CNV and in 11
      of the 12 eyes with occult CNV. Additionally, all but 1 eye with primary occult
      CNV and 6 of the 8 eyes with recurrent occult CNV could be reclassified in this
      study as having well-defined CNV. Overall, ICGV yielded additional information in
      17 of the 20 eyes with primary and recurrent occult CNV. Its clinical importance
      for the evaluation of early stages of AMD has still to be confirmed by future
      investigations. ICGV is recommended as a diagnostic examination in eyes with CNV
      poorly defined by fluorescein angiography.

PMID- 7523259
TI  - Bile induced acute oedematous pancreatitis in rats: non-parallel changes in
      pancreatic morphology and amylase release in vitro.
AB  - Pancreatic morphology and amylase release from isolated pancreatic acini in
      response to caerulein was studied in the course of an experimental bile induced
      acute pancreatitis without acinar necrosis. The inflammation was induced by
      retrograde microinfusion of 25 microliters bile into the rat bile pancreatic
      duct. A dissociation between functional and structural findings was seen. One
      hour after the bile injury, there was a transient change in acinar cell function.
      The response to stimulation by caerulein was reduced by 50%, whereas the
      sensitivity to caerulein was normal. There was oedema and an initial leucocyte
      infiltration of the gland. Six hours, one day, three days, and seven days after
      the bile injury, there was an acute interstitial oedematous pancreatitis with a
      modest polymorphonuclear leucocyte infiltration of the interstitium and
      widespread acinar vacuolisation. Morphological changes were most pronounced at
      the third postoperative day. Acinar amylase release, however, was normal both in
      terms of sensitivity and responsiveness to stimulation. These results show that
      bile injury may result in an initial disturbance of acinar cell function. Normal
      acinar amylase release prevailing in the course of the inflammation suggests that
      disturbance of the acinar amylase secretory response is not a primary stimulant
      of the inflammation before the development of acinar necrosis.

PMID- 7523261
TI  - Epithelium modulates the kinetics of the response to substance P and its
      intrinsic activity in the guinea-pig trachea.
AB  - The contractile response of guinea-pig tracheal preparations with or without
      epithelium to substance P has been studied in the presence or absence of
      thiorphan, an endopeptidase 24.11 inhibitor, paying special attention to the
      kinetics of the response. Without thiorphan, the response to substance P was
      greater in tracheal preparations without epithelium than in tracheal preparations
      with epithelium. The concentration-response curve was shifted to the left in the
      absence of the epithelium. In the presence of 10 microM thiorphan, the maximal
      contractile response induced by single doses of substance P (0.1 to 10 microM)
      was lower in tracheal preparations without epithelium. The maximal responses
      required 10 min in tracheal preparations with epithelium and 2 min in tracheal
      preparations without epithelium. These epithelium-dependent differences of
      reactivity remained in the presence of lipoxygenase or cyclooxygenase inhibitors
      and of selective antagonists of muscarinic, serotoninergic and histaminergic
      receptors, after the pre-treatment of tissues with capsaicin or compound 48/80
      and in the presence of tetrodotoxin. The profile of the cumulative concentration
      response curves for substance P was largely dependent on the time between two
      successive doses. When this time was short (2-4 min), curves established with or
      without the epithelium were parallel and both reached similar maximal values
      (2696 +/- 214 mg and 2780 +/- 62 mg, respectively). The curve in tracheal
      preparations without epithelium was slightly shifted to the left (EC50s: 24 +/-
      10 nM and 78 +/- 19 nM). When this time was longer (10 min, ie corresponding to
      the time required for a full response to a single dose in intact trachea) the
      potency of substance P was not modified (EC50s: 13 +/- 3 nM and 52 +/- 11 nM),
      but a lower maximal response was observed with tracheal preparations without
      epithelium (1440 +/- 182 mg and 2832 +/- 209 mg). Similar results were observed
      with neurokinin A and neurokinin B. Thus, the removal of the epithelium led to a
      more rapid contraction and to a decrease of the maximal response to neurokinins,
      ie a decreased intrinsic activity, a property known to be drug- and tissue
      dependent. These data suggest that the intrinsic activity of drugs depends on the
      cellular environment of the target cells in a tissue and is partly related to the
      diffusion and metabolism of drugs and to drug-induced hyporeactivity of the
      target cells.

PMID- 7523258
TI  - The significance of vitronectin in proliferative diabetic retinopathy.
AB  - Vitronectin, an integrin-binding a-1-glycoprotein with potent cell-adhesion and
      proliferation-mediating properties, has been shown to be incorporated in
      surgically removed membranes from patients with proliferative vitreoretinopathy
      (PVR), proliferative diabetic retinopathy (PDR) and macular pucker. Therefore we
      developed an ELISA technique to quantify levels of vitronectin in human vitreous
      and plasma samples in order to be able to evaluate the significance of
      vitronectin in these different vitreoretinal diseases. Our results indicate a
      significant increase of vitronectin in all proliferative disorders except
      idiopathic macular pucker. Adjustment of all probes to equal total protein
      content yielded a significant increase only in PDR (type II diabetes). Plasma
      samples demonstrated a significant increase of vitronectin in patients with type
      II diabetes suffering from PDR. Therefore, break-down of the blood-retina barrier
      appears to be the most likely explanation for the increased levels of vitronectin
      in the vitreous. Our results indicate that vitronectin may not only be involved
      in the regulation of epiretinal membrane formation at significantly higher levels
      in patients with type II diabetes, but the increase of vitronectin in diabetic
      plasma may also help to explain the pathological alteration of the coagulation
      cascade in diabetics.

PMID- 7523260
TI  - Comparison of pancreatic morphology and exocrine functional impairment in
      patients with chronic pancreatitis.
AB  - A comparative analysis of pancreatic morphology and exocrine function was
      performed prospectively in 48 patients. All patients had transabdominal
      ultrasound, computed tomography, endoscopic retrograde pancreatography, and a
      secretin-caerulein test. Classification of ultrasound, computed tomography, and
      pancreatogram findings was based on the Cambridge classification. In 10 patients,
      no pancreatic duct changes were detected on pancreatography. Equivocal (Cambridge
      I), mild to moderate (Cambridge II), and considerable ductal changes (Cambridge
      III) were found in 10, 12, and 16 patients, respectively. Computed tomography and
      ultrasound changes were found to correlate in 40-50%, 67%, and 94-100% of
      patients with Cambridge I, II, and III abnormal duct morphology, respectively. In
      patients with a normal pancreatogram, no patient had a functional impairment.
      Seventy per cent of the patients with equivocal pancreatic duct changes had
      dissociated, and 30% global, pancreatic insufficiency, while 50% of those with
      mild to moderate abnormal duct morphology manifested dissociated, and 50% global,
      functional impairment. All patients with considerable pancreatic duct changes had
      global pancreatic insufficiency. The results of this study confirm that normal
      endoscopic retrograde pancreatographic findings and Cambridge III ductal changes
      on endoscopic retrograde pancreatography correlate extremely well with normal
      pancreatic function and advanced functional insufficiency, respectively. As
      diagnostic tools, ultrasound and computed tomography are as sensitive as
      pancreatography only in chronic pancreatitis with considerable morphological
      changes.

PMID- 7523262
TI  - Anti-IgE induces the opening of non selective cation channels on human basophils.
AB  - Basophils play a major role in allergic reactions-particularly in late phase
      reactions-by releasing histamine and other mediators of inflammation. Although
      transmembrane ion fluxes are thought to play an important role in the modulation
      of histamine release, little is known about ion pathways through the basophil
      membrane. We thus studied human basophils from normal subjects (n = 25 cells)
      with the patch-clamp method. We observed that IgE-dependent activation of human
      basophils led to the opening of non selective cation channels with a 20pS
      conductance. This was obtained when the patch pipette was applied onto the cell
      surface and sealed onto it in order to measure transmembrane currents on a small
      surface of intact basophils (cell-attached configuration). Non selective channels
      with the same 20pS conductance were also observed when a membrane patch was
      detached from basophil and its inner side placed in a Ca(2+)-containing medium
      (inside-out configuration). These data are a first contribution of the patch
      clamp method in the understanding of ion movements in human basophils.

PMID- 7523263
TI  - [Analysis of Fas antigen gene expression in human thymocytes fractionated with
      discontinuous gradients using bovine serum albumin].
AB  - Premature thymocytes proliferate and differentiate from immature to mature T
      lymphocytes through out both positive and negative selections in thymus. The
      clonal deletion is a major mechanism of cell selection and mainly depends on
      apoptosis. Recently, Itoh et al. isolated cDNAs encoding Fas antigen which
      mediate apoptosis and is expressed on mouse thymocytes. Herein, I further
      attempted to examine the expression of Fas antigen gene in human thymocytes from
      thymus resected at cardiac operations. Human thymocytes were separated into 5
      fractions with discontinuous gradient using bovine serum albumin (BSA). They
      consisted of fractions I (BSA concentrations: 10-14%), II (14-16%), III (16-18%),
      IV (18-20%), and V (20-24%). Human thymocytes in each fraction were characterized
      regarding the rearrangement of T cell receptor (TCR) genes and the expression of
      human Fas antigen gene. Human thymocytes were divided into three sub populations
      according to their stages of differentiation and maturation. First population,
      thymocytes contained in fraction I, expressed interleukin 2 receptor alpha-chain
      (IL-2R alpha) and proliferated without the presence of recombinant IL-2 (rIL-2).
      Second, thymocytes contained in fraction II and III, expressed IL-2R alpha but
      could not proliferate without the presence of rIL-2. Third, thymocytes contained
      in fraction IV and V, could not express IL-2R alpha nor proliferate under any
      conditions assayed, and occupied over 90% of total human thymocytes in number.
      The southern blot analysis of T cell receptor beta-chain gene constant region (C
      beta) showed that C beta were rearranged in most of all thymocytes except for
      small population contained in fraction I. The reverse transcription-polymerase
      chain reaction (RT-PCR) analysis of Fas antigen gene expression revealed that the
      thymocytes in fraction I expressed Fas antigen gene more than those in any other
      fractions and that the thymocytes in fraction V expressed no Fas antigen gene.
      These results suggested that Fas antigen plays a minor role in the clonal
      deletion of postnatal human thymocytes.

PMID- 7523264
TI  - [Detection of amino acids on the agretopes of pigeon cytochrome c derived peptide
      p43-58 specifically bound to mouse MHC class II allelic products].
AB  - In our previous study it has been demonstrated that residues 46 and 54 on a
      pigeon cytochrome c derived peptide, 50V (AEGFSYTVANKNKGIT), work as agretopes
      (sites contact with MHC molecule) and residues 50 and 52 function as dominant
      epitopes (sites contact with TCR), when tri-molecular complexes are formed among
      50V, I-Ab molecule and TCR. 50V was substituted from aspartic acid to valine at
      position 50 of p43-58 that was derived from residues 43 to 58 of pigeon
      cytochrome c. Substitution of agretopic residues on 50V altered this I-Ab binding
      peptide to an I-Ak binding peptide, suggesting that positions 46 and 54 also
      worked as agretopes in I-Ak restricted T cell responses. In the present report I
      examined whether residues 46 and 54 of the p43-58 related peptides worked as
      agretopes in binding to products of other I-A haplotypes and tried to determine
      which amino acids on agretopes bound strongly with each I-A molecule. The p43-58
      related peptides with phenylalanine(F) at position 46 and alanine(A) at position
      54 bound tightly to I-Ab, I-Aq and I-A(s) molecules and stimulated T cells most
      potently in mice bearing these I-A products. In contrast, p43-58 related peptides
      carrying aspartic acid(D) at position 46 and A at position 54 bound most potently
      to I-Ak molecules, and the peptides with arginine(R) at position 46 and A at
      position 54 bound most efficiently to I-Av molecules. These findings demonstrate
      that the agretopic positions on p43 -58 related peptides are preserved in T cell
      responses restricted to each I-A haplotype studied, but the specific amino acids
      on the agretopes exist a priori for each I-A allele specific structure.

PMID- 7523265
TI  - Blood and plasma 5-hydroxytryptamine levels in patients with cirrhosis.
AB  - Serotoninergic mechanisms are thought to play a role in portal hypertension.
      Because this biomine is metabolized by the liver, peripheral blood and plasma
      levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid (the main
      metabolite of 5-hydroxytryptamine) were measured in 30 patients with cirrhosis.
      Whole-blood 5-hydroxytryptamine levels were significantly lower in patients with
      cirrhosis (158 +/- 28 nM) than in age-matched controls (332 +/- 19 nM), and no
      correlation was found between these levels and the severity of cirrhosis.
      Unconjugated plasma 5-hydroxytryptamine levels, an indication of the active form
      of 5-hydroxytryptamine, were significantly higher in patients with cirrhosis than
      in controls (6.8 +/- 1.7 nM and 3.4 +/- 0.5 nM, respectively), and in patients
      with cirrhosis these levels were higher in Pugh grade A than in Pugh grade C
      patients. Conjugated-plasma 5-hydroxytryptamine levels were not significantly
      different between patients with cirrhosis (32.2 +/- 8.1 nmol/L) and controls
      (16.4 +/- 1.4 nmol/L). Plasma 5-hydroxyindole acetic acid was significantly lower
      in patients with cirrhosis than in controls (1.5 +/- 0.1 nmol/L and 2.3 +/- 0.1
      nmol/L, respectively). In conclusion, this study shows that serotoninergic
      mechanisms are altered in patients with cirrhosis.

PMID- 7523268
TI  - Modulation of hepatic mRNA levels after administration of lipopolysaccharide and
      diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) to
      mice.
AB  - Administration of whole-cell diphtheria and tetanus toxoids and pertussis vaccine
      adsorbed (DTP vaccine) caused marked depression in the expression of mRNA for
      isozymes of cytochrome P-450 in the livers of endotoxin-responsive and
      nonresponsive mice. The levels of expression of mRNA for a polycyclic aromatic
      hydrocarbon-inducible (CYP1A2) and an ethanol-inducible (CYP2E1) form of P-450
      were reduced by 70% to 80% 8 to 12 hr after vaccination or Bordetella pertussis
      endotoxin administration. These effects are preceded by marked increases
      (threefold to sixfold) in mRNA expression for interleukin-6, interleukin-1 and
      tumor necrosis factor in both strains of mice, with maximal increases 1 to 2 hr
      after injection. This is the first demonstration that levels of cytokine mRNA are
      altered in the liver in response to DTP vaccine administration. The finding of
      increased cytokine mRNA in the livers of mice injected with vaccine supports a
      role for cytokines as mediators of the decreased levels of cytochrome P-450. In
      addition, inducible nitric oxide synthase mRNA expression is also increased after
      vaccine administration, with a peak at 4 hr. The temporal relationship of the
      increased cytokine mRNA expression, increased nitric oxide synthase and decreased
      expression of P-450 mRNAs suggests a mechanism by which cytokines mediate the
      induction of nitric oxide synthase, which increases nitric oxide and decreases
      the activities of some cytochromes P-450.

PMID- 7523270
TI  - Increased serum hepatitis C virus RNA levels among alcoholic patients with
      chronic hepatitis C.
AB  - Hepatitis viruses and alcohol are major causes of liver disease. This study was
      aimed at investigating the effect of alcohol intake on the replication of
      hepatitis C virus and the efficacy of interferon therapy. Fifty-three patients
      who were histologically proved to have chronic hepatitis C were tested. Of these,
      16 were diagnosed as habitual drinkers whose cumulative total consumption of
      alcohol was more than 100 kg or who had consumed at least 60 gm of ethanol daily
      for at least 5 yr. The quantities of hepatitis C virus RNA in serum were measured
      with a competitive assay that combined reverse transcription and polymerase chain
      reaction. The subjects received a 26-wk course of interferon-alpha therapy. There
      were no significant differences in age and ALT levels between habitual drinkers
      and nonhabitual drinkers. The titer of viral RNA (logarithmic transformed copy
      numbers per milliliter of serum) of habitual drinkers (8.5 +/- 0.5) was higher
      than that of nonhabitual drinkers (7.7 +/- 0.8) (p < 0.01). Neopterin levels in
      serum, a marker for the activation of cell-mediated immunity, were lower for
      habitual drinkers (5.7 +/- 1.5 pmol/ml) than for nonhabitual drinkers (8.1 +/-
      5.0 pmol/ml) (p < 0.01). Eleven of the nonhabitual drinkers (30%) were long-term
      responders whose alanine aminotransferase levels remained within normal range
      during the 24 wk after interferon therapy, whereas only one (6%) of the habitual
      drinkers was a long-term responder (p = 0.06). These findings suggest that
      alcohol intake increases hepatitis C virus RNA levels in serum--at least in part-
      impairment of cellular immunity, and modulates the efficacy of interferon
      therapy.

PMID- 7523267
TI  - Rapid induction of mRNAs for liver regeneration factor and insulin-like growth
      factor binding protein-1 in primary cultures of rat hepatocytes by hepatocyte
      growth factor and epidermal growth factor.
AB  - Liver regeneration factor belongs to the leucine-zipper family of transcription
      factors. It was originally cloned and characterized through differential
      screening of a regenerating rat liver cDNA library. The mRNA for liver
      regeneration factor-1 is barely detectable in normal rat liver but is
      dramatically induced after two-thirds hepatectomy, with a peak 1 to 3 hr after
      surgery. The nature of the signaling molecule(s) for this rapid induction is not
      known. It has been suggested that the liver regeneration factor-1 protein
      product, through complex interactions with other transcription factors such as c
      Jun and Jun-B, controls expression of genes that are required during the G1 phase
      of hepatic growth. Hepatocyte growth factor has been shown to be the most potent
      mitogen for hepatocytes in vitro and in vivo. Plasma levels of hepatocyte growth
      factor rapidly (within 30 min) increase after loss of hepatic parenchyma induced
      by partial hepatectomy or carbon tetrachloride treatment. It has been postulated
      that hepatocyte growth factor plays a crucial role in stimulating the hepatocyte
      to enter the cell cycle. In this communication, we report that addition of pure
      hepatocyte growth factor to primary cultures of rat hepatocytes in the absence of
      serum and insulin results in rapid and transient induction of liver regeneration
      factor-1 mRNA (more than 20-fold) with a peak of expression 1 hr after treatment.
      The levels of jun-B and c-fos mRNAs, which are also known to be induced during
      the early hours of liver regeneration, were also increased after treatment of
      isolated hepatocytes with hepatocyte growth factor.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7523266
TI  - Undulin RNA and protein expression in normal and fibrotic human liver.
AB  - We have analyzed the distribution, gene expression and cellular origin of
      undulin, a large extracellular matrix glycoprotein associated with mature
      collagen fibrils, in human liver by immunohistochemistry, Northern-blot analysis
      and in situ hybridization. In normal liver, undulin was distributed as densely
      packed fibers in portal tract stroma, and as fine fibers along sinusoids, and
      around central veins. Undulin ribonucleic acid expression was low in normal
      liver, and confined to mesenchymal cells of portal tract stroma, vessel walls and
      perisinusoidal space. In fibrotic liver, undulin deposition and gene expression
      were enhanced in fibrotic stroma and areas of fibrogenesis identified by the
      presence of active septa and inflammatory infiltrate. Undulin gene expression in
      fibrotic liver was exclusively localized in mesenchymal cells that could be
      identified by staining for vimentin, and partially for alpha-smooth muscle actin
      as (myo)fibroblasts, and possibly fat-storing cells. These data suggest that
      undulin is a constituent of the hepatic extracellular matrix of normal human
      liver, and that it participates in the rearrangement of connective tissue
      occurring in hepatic fibrosis.

PMID- 7523271
TI  - Influence of viral quasispecies on effectiveness of interferon therapy in chronic
      hepatitis C patients.
AB  - The quasispecies nature of hepatitis C virus genome distribution is most evident
      in hypervariable regions of the putative envelope 2 domain. Eight patients with
      chronic hepatitis C treated with interferon-alpha were studied as to
      heterogeneity of the hypervariable regions to clarify the implications of
      quasispecies. More than 10 recombinant clones generated from polymerase chain
      reaction-amplified products of the hypervariable regions were sequenced. The sets
      of clones derived from long-term responders before interferon therapy showed a
      significantly lower (p < 0.05) degree of sequence complexity of the hypervariable
      region 1 quasispecies than those from short-term ones or non-responders. The
      values of nucleotide diversity (the average number of nucleotide differences per
      site between two randomly chosen sequences) in hypervariable region 1 before
      interferon therapy were also significantly lower (p < 0.05) for long-term
      responders (mean, 2.31 x 10(-2)). In some cases, nucleotide diversity decreased
      remarkably during interferon therapy, whereas the values remained unchanged in
      other cases. In one interesting case, a short-term response was first noted with
      the nucleotide diversity decreasing from 13.98 x 10(-2) to 0.21 x 10(-2); namely,
      the diversity of the quasispecies was significantly reduced, and then a long-term
      response was observed after an additional course of interferon therapy. Thus, the
      degree of quasispecies' complexity and diversity of hypervariable region 1 was
      closely correlated with the responsiveness to interferon therapy in chronic
      hepatitis C patients, and thus may have some influence on interferon efficacy.

PMID- 7523269
TI  - Expression of the c-myc protooncogene product in cells infected with the
      hepatitis delta virus.
AB  - The intrahepatic accumulation of the c-myc protooncogene product was observed on
      immunofluorescence in each of six patients with chronic hepatitis delta virus
      infection who exhibited the hepatitis D antigen in their livers. The c-myc
      product was stained in the same nuclei that contained the hepatitis D antigen. C
      myc was not observed in acute hepatitis D or in cases of chronic hepatitis delta
      virus infection without expression of the hepatitis D antigen. The protooncogene
      product was detected in only 1 of 32 viral and nonviral liver disorders unrelated
      to hepatitis delta virus. To confirm these observations, we transfected HBsAg
      positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liver cell lines with
      a plasmid containing a hepatitis delta virus cDNA trimer under the control of the
      SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was
      barely detectable in mock-transfected PLC/PRF/5 or HepG2 cells, strong c-myc
      nuclear fluorescence was observed when these same cells were transfected with the
      hepatitis D antigen expression vector. Similar results were obtained after
      infection of HeLa cells with a recombinant vaccinia virus expressing the
      hepatitis D antigen. Detection of c-myc mRNA sequences by means of in situ
      hybridization suggested that the c-myc product accumulation was not due to
      increased amounts of its mRNA. The c-myc protein accumulates selectively in the
      livers of patients with chronic hepatitis delta virus infection and in the same
      nuclei that contain the hepatitis D antigen. The expression of c-myc in hepatitis
      D antigen-containing cells does not require the presence of hepatitis B virus
      infection.

PMID- 7523274
TI  - Alteration in growth regulation of hepatocytes in primary culture obtained from
      cirrhotic rat: poor response to transforming growth factor-beta 1 and
      interferons.
AB  - Cell growth appears to be controlled by positive and negative cell growth
      regulation. Little is known about the growth regulation of hepatocytes in the
      cirrhotic liver. Clarifying the responses of hepatocytes obtained from cirrhotic
      liver to various growth factors and growth inhibitory factors might aid
      understanding of alterations in growth regulation of the hepatocytes in the
      cirrhotic liver. We investigated the effects of hepatocyte growth factor,
      epidermal growth factor, heparin-binding epidermal growth factor-like growth
      factor, transforming growth factor-beta 1, interferon-alpha and interferon-gamma
      on the DNA synthesis of hepatocytes from cirrhotic and normal rats in primary
      culture. Cirrhosis was induced in male Sprague-Dawley rats by means of oral
      administration of 0.05% thioacetamide in drinking water for 4 mo. Hepatocytes
      were isolated by means of an in situ perfusion method, and DNA synthesis was
      assessed from the amount of DNA-incorporated [3H]thymidine. Stimulation of the
      DNA synthesis of hepatocytes by hepatocyte growth factor, epidermal growth factor
      and heparin-binding epidermal growth factor-like growth factor was not different
      between normal and cirrhotic rat liver. Transforming growth factor-beta 1
      inhibited the DNA synthesis of hepatocytes in both. However, the concentration of
      transforming growth factor-beta 1 giving a 50% inhibition of DNA synthesis was
      about two times higher in cirrhotic hepatocytes (0.11 ng/ml) than in normal
      hepatocytes (0.06 ng/ml). In cirrhotic hepatocytes, the expression of
      transforming growth factor-beta type II receptor gene was about 50% of that in
      normal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523272
TI  - Expression of mucin core protein of mammary type in primary liver cancer.
AB  - Expression of mucin core protein of mammary type (MUC-1 core protein) was
      investigated in primary hepatic carcinoma (25 cases of cholangiocarcinoma, 15
      cases of combined hepatocellular-cholangiocellular carcinoma and 18 cases of
      hepatocellular carcinoma) with monoclonal antibody DF3 and a standard
      avidinbiotin complex method. MUC-1 core protein was almost always expressed in
      cholangiocarcinoma and in the cholangiocarcinoma area of hepatocellular-cholangio
      cellular carcinoma to a varied degree, whereas such expression was virtually
      absent in hepatocellular carcinoma and the hepatocellular carcinoma areas of
      hepatocellular-cholangiocellular carcinoma. Nonneoplastic intrahepatic biliary
      epithelium, as well as hepatocytes, was virtually negative for this protein. In
      well-differentiated cholangiocarcinoma, this protein tended to be expressed on
      luminal surfaces, whereas poorly differentiated cholangiocarcinoma showed cell
      membranous or diffuse cytoplasmic staining patterns. Double staining with Alcian
      blue (pH 2.5) and immunostaining for MUC-1 core protein showed that although some
      parts of cancerous areas were positive for both stains, most cancerous areas were
      only positive for one. Alcian blue--positive areas were dominant over MUC-1 core
      protein--expressing areas in well-differentiated cholangiocarcinoma, whereas the
      reverse was the case in poorly differentiated cholangiocarcinomas and also in
      cholangiocarcinoma areas of hepatocellular-cholangiocellular carcinoma. This
      study is the first report to document that cholangiocarcinoma and
      cholangiocarcinoma areas of hepatocellular-cholangiocellular carcinoma express
      MUC-1 core protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523273
TI  - Pathogenic factors in cirrhosis with and without hepatocellular carcinoma: a
      multicenter Italian study.
AB  - We designed a multicenter cross-sectional study to evaluate the role of alcohol
      abuse, the hepatitis viruses and other pathogenic factors in cirrhosis and
      hepatocellular carcinoma. A total of 1,829 consecutive cirrhosis patients, with
      or without HCC, was enrolled over 6 mo in 21 centers throughout Italy. The
      etiological categories and diagnostic criteria were preestablished. The median
      age of the patients was 59 yr (range, 13 to 85 yr); 63.6% of the patients were
      graded as Child class A, 23.4% as Child class B and 13% as Child class C.
      Hepatitis C virus antibodies were found in 72.1% of cases (47.7% alone, 21.2%
      with alcohol abuse, 3.2% with hepatitis B virus); HBsAg was present in 13.8%
      (4.2% alone, 3.2% with hepatitis D virus, 3.2% with hepatitis C virus, 3% with
      alcohol abuse), alcohol abuse with no concomitant viral infection was recorded in
      8.7%, primary biliary cirrhosis was found in 1.8%, other causes were found in
      1.4% and cryptogenic cirrhosis was only present in 5.3%. Hepatocellular carcinoma
      was detected in 11.9% of patients (217 cases). The presence of hepatocellular
      carcinoma was more frequent in males than females (14.7% vs. 7.3%; p < 0.001) and
      increased with worsening Child class (8.3% in Child class A, 16.9% in Child class
      B, 19.9% in Child class C, p < 0.001). The highest prevalences of hepatocellular
      carcinoma were observed in hepatitis B virus infection, with or without alcohol
      abuse (20% and 16%, respectively) and in hepatitis C virus cirrhosis, with or
      without alcohol abuse (16% and 10.3%, p < 0.005).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7523275
TI  - Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas.
AB  - CD44, an integral membrane glycoprotein expressed by many cell types, serves as
      the principal transmembrane hyaluronate receptor and may be a determinant of
      metastatic and invasive behavior in carcinomas. The expression of CD44 in 23
      gastric adenocarcinoma and 12 peptic ulcer disease (PUD) resection specimens and
      gastric carcinoma cell lines HS746t and KATO III was examined by
      immunohistochemistry using the murine monoclonal antibody A3D8 on formalin-fixed,
      paraffin-embedded tissue or cells. Western blot analysis of whole cell lysates of
      KATO III and HS746t cells showed protein bands at 85 to 90 kd with KATO III cells
      expressing an additional band at 145 kd. In normal stomach gastric epithelium was
      negative. In PUD foveolar epithelium was focally positive, but staining did not
      correlate with the extent of gastritis. In carcinoma cases intensity of staining
      was progressively stronger comparing intestinal metaplasia with dysplasia with
      intramucosal carcinoma. Invasive carcinoma was invariably more strongly positive
      than dysplasia or intramucosal carcinoma. Twelve adenocarcinomas were weakly
      positive and 11 were strongly positive. The staining intensity of metastases (12
      cases) was the same or weaker than the primary tumor. For the 12 patients whose
      carcinomas were weakly positive, mean length of survival for the six who died was
      23.3 months. Five of the 11 patients whose carcinomas strongly expressed CD44
      died within the study period with a mean length of survival of 11.0 months. A key
      consequence of CD44 overexpression in gastric carcinomas may be development of
      the invasive phenotype and strong expression may indicate a poorer prognosis.

PMID- 7523276
TI  - Polymorphism in the human E-selectin gene detected by PCR-SSCP.
AB  - By using the non-isotopic single-strand conformation polymorphism (SSCP)
      technique to analyse products of the polymerase chain reaction (PCR), we detected
      a 561-adenine to cytosine substitution resulting in an amino acid exchange from
      serine to arginine at position 128 of the E-selectin gene. If this amino acid
      substitution has an effect on the adhesion of blood cells to the endothelium, the
      polymorphism could be of interest with respect to association studies in a number
      of pathological conditions, such as cardiovascular diseases.

PMID- 7523278
TI  - NMR microspectroscopy using 100 microns planar RF coils fabricated on gallium
      arsenide substrates.
AB  - A family of planar gold RF microcoils were fabricated using microlithography on a
      gallium arsenide substrate. The microcoils were used in 1H nuclear magnetic
      resonance (NMR) spectroscopy experiments at 300 MHz (7.05 T). These new
      microcoils are a key component in the design of integrated MR coils and
      amplifiers for NMR microspectroscopy.

PMID- 7523277
TI  - Purification of E. coli-synthesized Pan proteins and development of a Pan
      specific monoclonal antibody.
AB  - The helix-loop-helix (HLH) transcription factors, Pan-1 (E47) and Pan-2 (E12),
      are produced by the mechanism of alternative transcript splicing. Pan-1 and Pan-2
      were expressed in Escherichia coli, and a purification scheme was developed.
      Purified Pan-2 was used to immunize Smith-Webster mice and a hybridoma was
      generated that produced a monoclonal antibody (Yae) that specifically recognized
      both native and denatured Pan-1 and Pan-2. Deletion mapping and sequence transfer
      studies have localized the determinant recognized by the Yae antibody to the
      region 195-208 of Pan-2. This region is conserved in Pan-1 and Pan-2. The Yae
      antibody recognized in vitro-synthesized ITF-1, a third E2A (Pan) gene product
      also produced by the mechanism of alternative RNA splicing, but did not recognize
      the related HLH proteins, ITF-2, REB alpha, or REB beta. By Western blot assay of
      pancreatic acinar cells, the Yae antibody detected a single protein species of 72
      kD that comigrated with in vitro-synthesized Pan-1 and Pan-2.

PMID- 7523280
TI  - Fluorimetric probes of the individual and competitive binding of 1
      anilinonaphthalene-8-sulfonate, eosine and fluorescene to bovine serum albumin.
AB  - Fluorescence of 1-anilinonaphthalene-8-sulfonate (ANS) is greatly enhanced on its
      binding to bovine serum albumin (BSA). Fluorimetric titration shows that three
      ANS molecules bind per BSA molecule. The enhanced fluorescence of BSA-ANS is
      quenched by eosine (EOS); and one EOS physically displaces one ANS bound to BSA.
      The enhanced fluorescence of free ANS in the hydrophobic environment of the
      nonionic surfactant Triton X 100 is also quenched by EOS but by an energy
      transfer mechanism. The dye fluorescene (FLSN) also quenches the fluorescence of
      BSA-bound ANS, but by the energy transfer mechanism. The binding region of ANS in
      BSA has been speculated.

PMID- 7523282
TI  - Three-stranded (triplex) DNAs (RNAs): do they have a role in biology?
AB  - The first triplexes were homopolymer mixtures, e.g. dTn.dAn.dTn. More complex
      triplexes could be made on the basis that the base triads [symbol: see text] and
      [symbol: see text] containing Watson-Crick and Hoogsteen base pairs are
      isomorphous and so could be expected to give regular triple helices. It follows
      that such triplexes can only be formed from asymmetric DNAs with pyrimidines (Yn)
      in one strand and purines (Rn) in the complementary strand. Such triplexes
      Yn.Rn.Yn are formed with the above rules for pairing of triads with the Hoogsteen
      C protonated, [symbol: see text]. There are also triplexes built on the theme
      Yn.Rn.Rn (with triads T:A:A and [symbol: see text]). Here the triads are nearly
      isomorphous. Recently other triplexes without isomorphous triads at all have been
      obtained. Also RecA protein can promote triplex formation between a duplex DNA of
      any sequence and an homologous single-stranded DNA. The latter triplex is
      evidently important in recombination. The other possible roles for triplexes
      include transcriptional control, and roles in origins of replication and DNA
      condensation.

PMID- 7523279
TI  - Systemic and topical immunoglobulin treatment in immunocompromised patients.

PMID- 7523281
TI  - Biological microemulsions: Part IV--Phase behaviour and dynamics of
      microemulsions prepared with vegetable oils mixed with aerosol-OT, cinnamic
      alcohol and water.
AB  - Microemulsification of vegetable oils (ricebran, saffola, soyabean, sesame, palm
      and linseed) with water using aerosol-OT and cinnamic alcohol as mixed
      amphiphiles was studied. The biological microemulsions formed covered on the
      average approximately 27% of single phase area in the triangular phase diagram.
      The multiphasic zone for saffola was studied in detail, two- and three-phase
      zones were identified with patches of thick gel. The effect of temperature on the
      multiphase formation in the range 29-55 degrees C was also studied. The formation
      of multiphase and their proportions found to depend on the type of oil. The
      biological microemulsions at reasonable water/AOT mole ratio showed moderate
      increase in conductance with temperature. The viscosity of the microemulsions was
      high. Of the studied systems (sesame, saffola and ricebran) the viscosity of the
      first two decreased with the rate of shear whereas that of ricebran increased.
      When cinnamic alcohol was used as the oil, the trend of viscosity was similar to
      that of sesame and saffola.

PMID- 7523283
TI  - [The autoimmune dermatosis bullous pemphigoid: deposition and activation of
      plasminogen in affected epidermis].
AB  - Autoimmune dermatoses are associated with antibody deposition, complement
      activation and subsequent tissue destruction. Plasmin-mediated proteolysis is
      thought to be one element of tissue destruction in autoimmune bullous dermatoses
      such as bullous pemphigoid. Biochemical and immunological studies on bullous
      pemphigoid skin blister fluid disclosed plasmin/alpha 2-antiplasmin and putative
      plasmin/alpha 2-macroglobulin complexes. Since the formation of plasmin/inhibitor
      complexes requires active plasmin, our findings indicate previous activation of
      plasminogen to plasmin in skin lesions.

PMID- 7523285
TI  - [Molecular characterization of allergens].
AB  - Allergenic source material consists of a great number of single components of
      which only a small number is IgE-reactive. Since allergenic source material is
      the basis of diagnostics and immunotherapy, there is a strong interest in
      identification, characterization and quantification of allergens. A further
      reason of interest is to explain the pathomechanism of the type I allergy. The
      structure of allergens is of central importance, because only a small number of
      antigens are allergens and the structure of these components is essential in
      giving rise to symptoms. The process and further prospects of molecular
      characterization of allergens are described and grass pollen allergens are used
      as paradigm. Allergies are an excellent model to study the meaning of specificity
      in immunologic disorders.

PMID- 7523284
TI  - [Reconstitution of immunoglobulin production in patients with variable
      immunodeficiency syndrome (CVI) by the CD40 system and IL-10].
AB  - Common variable immunodeficiency (CVI) is widely believed to involve a primary B
      cell defect, however, there is increasing evidence of T cell dysfunction in these
      patients. To test the hypothesis that B cells of patients with CVI are not
      defective, we investigated whether immunoglobulin production can be induced by
      activation through the CD40 system. Our results show that 6 of 7 children with
      CVI produced IgG when B cells were activated through CD40 plus IL-10. In most
      patients, IgM and IgA production were also induced. However, we could demonstrate
      that failure of immunoglobulin production was not due to a defective CD40 ligand
      expression on T cells. Taken together, our data show that B cells of patients
      with CVI are functionally normal when activated through CD40 plus IL-10. IL-10
      seems to be more effective than IL-2 in restoration of immunoglobulin production
      in such patients.

PMID- 7523286
TI  - Inhibition of macrophage-induced, antigen-specific T-cell proliferation by poly
      I:C role of suppressor macrophages.
AB  - Poly I:C treatment can inhibit the ability of macrophages (M phi) to induce
      antigen-specific T-cell proliferation. This study investigated whether this
      inhibition is the result of suppressor or cytotoxic activity. Pretreatment of M
      phi with indomethacin in vivo, in vitro or both failed to reverse the inhibition
      of T-cell proliferation induced by poly I:C-treated, keyhole limpet haemocyanin
      (KLH)-pulsed M phi, suggesting that prostaglandin production does not mediate the
      inhibition of T-cell proliferation. The transfer of supernatants from cultures
      containing poly I:C-treated, KLH-pulsed M phi to cultures containing saline
      treated, KLH-pulsed M phi and T cells did not inhibit T-cell proliferation,
      suggesting that the inhibition of T-cell proliferation by poly I:C is not
      mediated by the production of soluble suppressor factors. As addition of poly I:C
      treated, KLH-pulsed M phi to cultures containing saline-treated, KLH-pulsed M phi
      did not significantly inhibit KLH-specific T-cell proliferation, the inhibition
      of T-cell proliferation is also not mediated by direct cell contact or short
      range soluble suppressor factors. In addition, poly I:C-treated, KLH-pulsed M phi
      did not induce cytolysis of syngeneic T cells. These results indicate that
      cytotoxic or suppressor effector functions of M phi are not involved in the
      mechanism by which poly I:C inhibits M phi-induced, antigen-specific T-cell
      proliferation.

PMID- 7523289
TI  - Demonstration of the interaction between the CD23 molecule and the galactose
      residue of glycoproteins.
AB  - The CD23 molecule is a low-affinity receptor for IgE and has a marked homology in
      amino acid sequence with C-type animal lectins, including asialoglycoprotein
      receptor. We tested whether the CD23 antigen can indeed interact with the sugar
      chain of glycoproteins. Detergent extract of the membrane component from Epstein
      Barr Virus (EBV)-transformed human B-cell line, L-KT9 cells, was incubated with
      asialofetuin (ASF)-coupled Sepharose, and bound proteins were effectively eluted
      by 0.3 M lactose or galactose which were among the competitive sugars tested. In
      this eluate, the CD23 molecule was detected by an immunoblotting technique.
      Because fetuin has both an N- and O-type sugar chain on the molecule, we tested
      which type of sugar chain can interact with CD23. The CD23 molecule interacted
      with asialocasein having a sugar chain with the Gal-GalNAc structure with
      asialobovine submaxillary mucin having the GalNAc structure, and also with ASF;
      however, it faintly interacted with ASF after removal of the O-type sugar chain
      by beta-elimination. These results showed that the CD23 molecule can, indeed,
      interact with the galactose residue, especially with the Gal-GalNAc rather than
      the Gal-GlcNAc structure of the terminal sugar chain of glycoproteins.

PMID- 7523287
TI  - Studies on the thymus of non-obese diabetic (NOD) mice: effect of transgene
      expression.
AB  - The non-obese diabetic (NOD) mouse is a good model of insulin-dependent diabetes
      mellitus. Autoreactive T cells may play a fundamental role in disease initiation
      in this model, while disregulation of such cells may result from an abnormal
      thymic microenvironment. Diabetes is prevented in NOD mice by direct introduction
      of an E alpha d transgene (NOD-E) or a modified I-A beta chain of NOD origin (NOD
      PRO or NOD-ASP). To investigate if disease pathology in NOD mice, protection from
      disease in transgenic NOD-E and NOD-PRO and partial protection from disease in
      NOD-ASP can be attributed to alterations in the thymic microenvironment,
      immunohistochemical and flow cytometric analysis of the thymi of these mouse
      strains was studied. Thymi from NOD and NOD-E mice showed a progressive increase
      in thymic B-cell percentage from 12 weeks of age. This was accompanied by a
      concomitant loss in thymic epithelial cells with the appearance of large
      epithelial-free areas mainly at the corticomedullary junction, which increased in
      size and number with age and contained the B-cell clusters. Such thymic B cells
      did not express CD5 and were absent in CBA, NOD-ASP and NOD-PRO mice as were the
      epithelial cell-free spaces, even at 5 months of age. Therefore the mechanisms of
      disease protection in the transgenic NOD-E and NOD-ASP/NOD-PRO mice may differ if
      these thymic abnormalities are related to disease.

PMID- 7523290
TI  - Novel heterogeneity of the leucocyte common antigen (CD45): disulfide-bound
      heterodimers between CD45 and an 80 kDa polypeptide.
AB  - The leukocyte common antigen, CD45, is one of the major glycoproteins on cells of
      hemopoietic origin showing considerable heterogeneity in both structure and
      expression. Biochemical heterogeneity has been attributed to differences in the
      primary sequence and glycosylation. In this paper we report an additional basis
      for generation of heterogeneity by revealing that CD45 can form disulfide-bound
      heterodimers with an 80 kDa polypeptide. Since a respectable fraction of the CD45
      molecules is involved in heterodimer formation, it is suggested that the 80 kDa
      polypeptide could be involved in the regulation of CD45 function.

PMID- 7523288
TI  - Anergy of antigen-specific T lymphocytes is a potent mechanism of intravenously
      induced tolerance.
AB  - Intravenous (i.v.) injection of an antigen before immunization has been shown to
      be a potent way to induce suppression at the T-cell level. In this study we
      demonstrate an almost complete suppression of arthritis (using antigen-induced
      arthritis as a model) by i.v. injection of 100 micrograms hen egg lysozyme (HEL)
      7 days before immunization. Underlying mechanisms, including suppression by CD8+
      T lymphocytes, suppression by T-helper 2 (Th2) or anergy of antigen-specific T
      lymphocytes, were studied. In vivo treatment with either anti-CD8 or anti
      interleukin-4 (IL-4) could not abrogate i.v.-induced tolerance. Lymphocyte
      stimulation assays showed reduced antigen-specific proliferative responses and IL
      2 production in tolerized mice. The possible role of soluble suppressive
      cytokines was examined in vitro by adding anti-IL-4, anti-IL-10 or anti
      transforming growth factor-beta (TGF-beta). Neutralization of these factors could
      not diminish suppression. Finally, anergy of antigen-specific T lymphocytes was
      tested as a possible mechanism for i.v.-induced tolerance. Results demonstrated
      that reduced proliferative T-cell responses were reversible: incubation of
      tolerized lymph node cells for 5 days in added recombinant (r)IL-2 fully restored
      proliferative capacity back to normal. We therefore conclude that the main
      mechanism of i.v.-induced tolerance in our model is anergy of antigen-specific T
      lymphocytes.

PMID- 7523291
TI  - Voltage-dependent ion channels in glial cells.
AB  - Glial cells, although non-excitable, express a wealth of voltage-activated ion
      channels that are typically characteristic of excitable cells. Since these
      channels are also observed in acutely isolated cells and in brain slices, they
      have to be considered functional in the intact brain. Numerous studies over the
      past 10 years have yielded detailed characterizations of glial channels
      permitting comparison of their properties to those of their neuronal
      counterparts. While for the most part such comparisons have demonstrated a high
      degree of similarity, they also provide evidence for the expression of some
      uniquely glial ion channels. An increasing number of studies indicate that the
      expression of "glial" channels is influenced by the cells' microenvironment. For
      example, the presence of neurons can induce or inhibit (depending on the
      preparation and type of channel studied) the expression of glial ion channels.
      Like ion channels in excitable cells, glial channels can be functionally
      regulated by activation of second-messenger pathways, allowing for short-term
      modulation of their membrane properties. Although the extent to which most of the
      characterized ion channels are involved in glial function is presently unclear, a
      growing body of data suggests that certain channels play an active role in glial
      function. Thus inwardly rectifying K+ channels in concert with delayed rectifying
      K+ channels are thought to be involved in the removal and redistribution of
      excess K+ in the brain, a process referred to as "spatial buffering". Glial K+
      channels may also be crucial in modulating glial proliferation. Cl- channels and
      stretch-activated cation channels are believed to be involved in volume
      regulation. Na+ channels appear to be important in fueling the glial Na+/K(+)
      pump, and Ca2+ channels are likely involved in numerous cellular events in which
      intracellular Ca2+ is a critical second messenger.

PMID- 7523293
TI  - Parameters that influence the efficiency of processing antigenic epitopes
      expressed in Salmonella typhimurium.
AB  - We investigated parameters that affect the efficiency with which antigenic
      epitopes from Salmonella typhimurium are processed for presentation to T
      lymphocytes. As a model system, the hen egg white lysozyme 52-61 [HEL(52-61)]
      epitope, which binds the murine major histocompatibility complex class II (MHC
      II) molecule I-Ak, was expressed in soluble fusion proteins in S. typhimurium.
      Murine peritoneal macrophages mediated phagocytic processing of viable S.
      typhimurium expressing fusion proteins of the HEL epitope for presentation via I
      Ak regardless of the bacterial compartment in which the epitope was contained
      (i.e., surface exposed, facing the periplasmic space, or in the cytoplasm). Minor
      differences in processing efficiency observed with different epitope
      compartmentalizations could be overcome by altering the relative expression
      level, indicating that epitope abundance is an important factor for efficient
      processing of epitopes from S. typhimurium. This processing pathway required
      phagocytosis of bacteria followed by passage through an acidic compartment,
      suggesting a pathway involving phagolysosomal degradation of the bacteria to
      liberate epitopes that bind MHC-II. HEL(52-61) was processed more efficiently
      from heat-killed S. typhimurium than from viable bacteria, and in addition, the
      HEL epitope was processed more efficiently from a rough lipopolysaccharide (LPS)
      strain than from its isogenic smooth LPS counterpart, most likely because of
      enhanced phagocytosis of the rough LPS strain. These data suggest that the
      efficiency of epitope processing from S. typhimurium for presentation via MHC-II
      is affected by bacterial viability, epitope abundance, and LPS phenotype, factors
      which may be important to consider in development of recombinant S. typhimurium
      vaccine strains.

PMID- 7523295
TI  - Lymphocyte proliferation in response to immunodominant antigens of Brucella
      abortus 2308 and RB51 in strain 2308-infected cattle.
AB  - Lymphocyte proliferation in response to proteins from the Brucella abortus strain
      2308 (S2308) and the lipopolysaccharide (LPS) O-antigen-deficient mutant of
      S2308, strain RB51 (SRB51), was measured in S2308-infected cattle following
      abortion. Supramammary and superficial cervical lymph node lymphocytes from
      infected cattle proliferated most when incubated with 27- to 18-kDa proteins of
      S2308 or SRB51. Proteins of SRB51, which contained no LPS O antigens, induced
      lymphocyte proliferation similar to that induced by S2308 proteins, which
      contained LPS O antigens. These results indicate that 27- to 18-kDa proteins, but
      not LPS O antigens, of S2308 and SRB51 are immunodominant in S2308-infected
      cattle as assessed by lymphocyte proliferation assays.

PMID- 7523292
TI  - High-resolution mapping of B-cell epitopes within an antigenic sequence from
      Eimeria tenella.
AB  - Overlapping hexapeptides representing part of an Eimeria tenella antigenic
      sequence, shown to induce partial immunity to homologous challenge in chickens,
      were synthesized on polypropylene pins (Pepskan technique; Cambridge Research
      Biochemicals, Cambridge, United Kingdom). The binding to these hexapeptides of
      antibodies from chickens infected and rabbits immunized with five species of
      Eimeria was studied, using the coated pins as the solid phase of an enzyme-linked
      immunoassay. Antibody binding to most regions of the sequence was demonstrated,
      with peak areas of antigenicity correlating with the most hydrophilic regions. A
      particularly hydrophilic and antigenic area towards the N terminus of the
      sequence consists of a peptide motif repeated five times in the native antigen.
      Homologous antisera (chicken and rabbit anti-E. tenella antisera) differed in
      their pattern of reactivity from heterologous sera raised against other Eimeria
      species. While the former bound to fewer of the hexapeptides than the latter,
      they did so very strongly, indicating affinity maturation of the antibody
      response to E. tenella-specific sequences. No antibody reactivity to two regions
      of the sequence was detected. These regions occur in relatively hydrophilic areas
      and so are unlikely to be situated in transmembrane domains or in the interior of
      globular proteins. Synthetic peptides, as used in these experiments, make
      possible analysis of the fine specificity of immune responses and thus have a
      role to play in the development of novel vaccines for the control of coccidiosis.

PMID- 7523294
TI  - Pore formation by the Escherichia coli alpha-hemolysin: role for mediator release
      from human inflammatory cells.
AB  - The Escherichia coli alpha-hemolysin represents a potent stimulus for
      inflammatory mediator release (O2-, beta-glucuronidase release, and leukotriene
      generation) from human polymorphonuclear granulocytes, for histamine release from
      a suspension of human lymphocyte/monocyte basophil cells (LMB), and for serotonin
      release and 12-hydroxyeicosatetraenoic acid generation from human platelets. In
      contrast, the E. coli alpha-hemolysin leads to a downregulation of cytokine
      release (interleukin-1 beta [IL-1 beta], IL-6, and tumor necrosis factor alpha)
      from human LMB. Recently, it became apparent that the E. coli alpha-hemolysin is
      composed of several functional structures. We analyzed the role of pore
      formation, pore stability, and calcium-dependent membrane binding for
      inflammatory mediator release by using washed bacteria as well as culture
      supernatants of isogenic recombinant E. coli strains expressing no hemolysin (Hly
      ), the wild-type hemolysin (Hly+), or hemolysin molecules deficient or modulated
      in defined functions (pore formation, calcium-dependent membrane binding, or pore
      stability). In human granulocytes and platelets, mutant hemolysin with enhanced
      pore stability did not lead to a further increase in induction; mutant hemolysin
      deficient in pore-forming activity or calcium-dependent membrane binding no
      longer induced leukotriene B4 generation or beta-glucuronidase release compared
      with the wild-type hemolysin. Similar results were obtained with regard to
      histamine release from human LMB. The induction of cytokine release from human
      LMB differed depending on the type of mutant E. coli alpha-hemolysin. The wild
      type hemolysin, the mutant hemolysin with enhanced pore-forming activity, and, to
      a lesser degree, the mutant hemolysin deficient in pore-forming activity
      decreased cytokine release (IL-1 beta, IL-6, IL-8, and tumor necrosis factor)
      compared with untreated cells. In contrast, the mutant hemolysin deficient in
      calcium-dependent membrane binding led to an increase of up to 50% in cytokine
      release compared with that by unstimulated cells. Our results indicate that
      simultaneous expression of the pore-forming and calcium-dependent membrane
      binding activities of the hemolysin molecule was necessary to obtain the full
      cellular inflammatory response pattern observed with the wild-type hemolysin.

PMID- 7523296
TI  - Characterization of rhoptry proteins of Eimeria tenella sporozoites: antigenic
      diversity of rhoptry epitopes within species of the genus Eimeria and among three
      asexual generations of a single species, E. tenella.
AB  - Rhoptry organelles from sporozoites of the apicomplexan parasite Eimeria tenella
      contain at least 60 independent polypeptides that can be resolved by two
      dimensional gel electrophoresis. Rhoptries from three species of Eimeria that
      infect chickens share very few antibody cross-reactive epitopes, and there is
      poor conservation of epitopes among three distinct asexual generations of zoites
      within the developmental life cycle of a single parasite, E. tenella.

PMID- 7523297
TI  - Soluble peptidoglycan-induced monokine production can be blocked by anti-CD14
      monoclonal antibodies and by lipid A partial structures.
AB  - We have investigated the interaction of soluble peptidoglycan (sPG), in
      comparison with lipopolysaccharide (LPS), with human mononuclear cells (MNC) by
      determining the capacity of sPG to induce interleukin-6 (IL-6) and IL-1 release.
      In addition, we investigated the modulation of their interaction by anti-CD14
      monoclonal antibody and by partial structures of LPS. We found that sPG, like
      LPS, was able to induce IL-6 and IL-1 production by MNC. However, dose-response
      experiments revealed that at least 3,000 ng of sPG per ml was necessary for
      induction, whereas the optimal LPS concentration was 1 ng/ml. Anti-CD14
      monoclonal antibody reduced sPG- and LPS-induced IL-6 and IL-1 production.
      Moreover, partial structures of LPS were able to reduce monokine production
      induced by sPG and LPS. We conclude that sPG constitutes, like LPS, an
      inflammatory cytokine inducer and that CD14 is involved in the activation of
      human monocytes not only by LPS but also by sPG.

PMID- 7523300
TI  - Chlamydia trachomatis serovar L2 induces protein tyrosine phosphorylation during
      uptake by HeLa cells.
AB  - Chlamydia trachomatis L2 is an obligate intracellular microorganism with a unique
      biphasic life cycle. The extracellular form, the elementary body (EB), is
      infectious but metabolically inactive. Attachment of EBs to host cells is
      medicated by a heparan sulfate-like glycosaminoglycan. Following attachment, the
      EB is internalized within a membrane-bound vesicle, and during the first 8 h of
      infection the vesicles are transported to a perinuclear location where they
      aggregate and fuse. By use of a monoclonal antibody against phosphotyrosine, we
      showed that three classes of proteins are tyrosine phosphorylated: a triple band
      of 68, 66, and 64 kDa, a 97-kDa band, and a 140-kDa band. The phosphorylation
      could be detected by immunoblotting from 15 min after infection of HeLa cells. We
      followed the movement of the EBs and the tyrosine phosphorylation of proteins by
      double-labelling immunofluorescence microscopy with the same monoclonal anti
      phosphotyrosine antibody and a polyclonal antibody against the C. trachomatis L2
      outer membrane complex. During the first 8 h of infection, the phosphorylation
      colocalized with EBs. Sixteen hours after infection, EBs have reorganized to the
      replicating reticulate bodies, forming an inclusion. At this time,
      phosphorylation was seen as dotted spots in the periphery of the inclusion.

PMID- 7523298
TI  - Identification of a new locus involved in expression of Haemophilus influenzae
      type b lipooligosaccharide.
AB  - Previous studies have shown that changes in the expression of the Haemophilus
      influenzae type b (Hib) lipooligosaccharide (LOS) epitope reactive with
      monoclonal antibody (MAb) 5G8 can be correlated with alterations in the virulence
      of some Hib strains. To identify the locus involved in expression of this
      particular LOS epitope, a genomic library was constructed in the plasmid shuttle
      vector pGJB103 from Hib strain DL42, which constitutively expressed LOS reactive
      with MAb 5G8. This library was used to transform a second Hib strain (DL180) that
      normally does not express this LOS epitope, and a recombinant clone was
      identified that bound MAb 5G8. Subcloning of different regions of the Hib DL42
      DNA insert in this recombinant plasmid determined that a 1.9-kb EcoRI fragment,
      designated lex-2, was responsible for transforming Hib strain DL180 to reactivity
      with MAb 5G8. Nucleotide sequence analysis revealed the presence of two
      contiguous open reading frames (ORFs) in lex-2, the first of which contained 18
      tandem repeats of the nucleotide tetramer GCAA near its 5' end. Sequence analysis
      of PCR-derived products from MAb 5G8-reactive and -nonreactive Hib DL180 colonies
      established that 18 GCAA repeats were associated with expression of the LOS
      epitope that bound MAb 5G8. Mutational analysis determined that a functional ORF
      2 was essential for expression of the MAb 5G8-reactive LOS epitope. The
      nucleotide tetramer GCAA repeat present in ORF 1 was also detected in at least
      two different chromosomal regions in all Hib strains tested. The availability of
      the cloned lex-2 locus should facilitate future analysis of the complex
      regulatory mechanisms involved in expression of LOS epitopes by this pathogen.

PMID- 7523299
TI  - Low levels of vitronectin and clusterin in acute meningococcal disease are
      closely associated with formation of the terminal-complement complex and the
      vitronectin-thrombin-antithrombin complex.
AB  - Patients with terminal complement deficiencies and thus impaired lytic efficiency
      have a highly increased likelihood of contracting invasive meningococcal
      infections but generally experience a mild disease course. Deficiencies of lysis
      inhibitors might therefore be associated with severe disease. We have quantified
      the complement lysis inhibitors vitronectin and clusterin, as well as complexes
      containing the proteins, in plasma from patients with acute meningococcal
      disease. At hospital admission, the median vitronectin concentrations were 0.10
      (range, 0.04 to 0.17) g/liter in 10 septic patients and 0.19 (0.09 to 0.47)
      g/liter in 14 nonseptic patients (P = 0.001). The corresponding clusterin
      concentrations were 0.09 (0.01 to 0.13) and 0.14 (0.06 to 0.29) g/liter (P =
      0.005). The vitronectin-thrombin-antithrombin complex concentration was 1.8 (0.22
      to 35.6) arbitrary units (AU)/ml in septic patients, but the complex was not
      detectable in most nonseptic patients (< 0.10 to 0.16 AU/ml) (P < 0.0001). The
      corresponding levels of the terminal complement complex (contains vitronectin and
      clusterin) were 4.4 (3.6 to 20.1) and 2.6 (1.6 to 4.7) AU/ml (P = 0.0005). We
      found no evidence of constitutively low levels of vitronectin or clusterin in
      patients contracting meningococcal disease. The low levels of the proteins may
      partly be explained by hemodilution, extravasation, and increased consumption due
      to incorporation into complexes which are quickly removed from circulation.

PMID- 7523301
TI  - An endo-acting proline-specific oligopeptidase from Treponema denticola ATCC
      35405: evidence of hydrolysis of human bioactive peptides.
AB  - An endo-acting proline-specific oligopeptidase (prolyl oligopeptidase [POPase],
      EC 3.4.21.26) was purified to homogeneity from the Triton X-100 extracts of cells
      of Treponema denticola ATCC 35405 (a human oral spirochete) by a procedure that
      comprised five successive fast protein liquid chromatography steps. The POPase is
      a cell-associated 75- to 77-kDa protein with an isoelectric point of ca. 6.5. The
      enzyme hydrolyzed (optimum pH 6.5) the Pro-pNA bond in carbobenzoxy-Gly-Pro-p
      nitroanilide (Z-Gly-Pro-pNA) and bonds at the carboxyl side of proline in several
      human bioactive peptides, such as bradykinin, substance P, neurotensin,
      angiotensins, oxytocin, vasopressin, and human endothelin fragment 22-38. The
      minimum hydrolyzable peptide size was tetrapeptide P3P2P1P'1, while the maximum
      substrate size was ca. 3 kDa. An imino acid residue in position P1 was absolutely
      necessary. The hydrolysis of Z-Gly-Pro-pNA was potently inhibited by the
      following, with the Ki(app) (in micromolar) in parentheses: insulin B-chain
      (0.7), human endothelin-1 (0.5), neuropeptide Y (1.7), substance P (32.0), T
      kinin (4.0), neurotensin (5.0), and bradykinin (16.0). Chemical modification and
      inhibition studies suggest that the POPase is a serine endopeptidase whose
      activity depends on the catalytic triad of COOH ... Ser ... His but not on a
      metal. The amino acid sequence around the putative active-site serine is Gly-Gly
      Ser-Asn-Pro-Gly. The enzyme is suggested to contain a reactive cysteinyl residue
      near the active site. Amino acid residues 4 to 24 of the first 24 N-terminal
      residues showed a homology of 71% with the POPase precursor from Flavobacterium
      meningosepticum and considerable homology with the Aeromonas hydrophila POPase.
      The ready hydrolysis of human bioactive peptides at bonds involving an imino acid
      residue suggests that enzymes like POPase may contribute to the chronicity of
      periodontal infections by participating in the peptidolytic processing of those
      peptides.

PMID- 7523302
TI  - A surface epitope undergoing high-frequency phase variation is shared by
      Mycoplasma gallisepticum and Mycoplasma bovis.
AB  - We have recently reported that three distinct size- and phase-variable surface
      lipoproteins (Vsps) of the bovine pathogen Mycoplasma bovis possess a common
      epitope recognized by monoclonal antibody 1E5. In the present study, we show that
      this epitope is also present on a size-variant protein (PvpA) of the avian
      pathogen Mycoplasma gallisepticum. Application of monoclonal antibody 1E5 in
      Western immunoblot analysis of Triton X-114 phase-fractionated proteins and in
      colony immunoblots, as well as in trypsin and carboxypeptidase digestion
      experiments, has demonstrated that (i) PvpA is an integral membrane protein with
      a free C terminus, (ii) the shared epitope is surface exposed, and (iii) PvpA is
      subjected to high-frequency phase variation in expression. By using serum
      antibodies from M. gallisepticum-infected chickens, we were able to demonstrate
      the immunogenic nature of PvpA and identify three additional highly immunogenic
      Triton X-114 phase proteins (p67, p72, and p75) also undergoing high-frequency
      phase variation spontaneously and independently. Metabolic labeling experiments
      with [14C]palmitate and [14C]oleate revealed that PvpA, in contrast to p67, p72,
      and p75, is not lipid modified. Southern blot hybridization with restriction
      fragments carrying the pvpA gene of M. gallisepticum or the vspA gene of M. bovis
      against digested genomic DNA of the two Mycoplasma species indicated the absence
      of genetic relatedness between the pvpA and vspA genes. The apparent complexity
      of the antigenic variation phenomenon in M. gallisepticum is discussed.

PMID- 7523305
TI  - Endothelial cell proliferation associated with lesions of murine systemic
      candidiasis.
AB  - Neovascularization is associated with tumor growth and some inflammatory diseases
      but has not been reported to be induced by infectious agents. In a mouse model of
      systemic Candida albicans infection, extensive endothelial cell proliferation was
      seen in the periphery of brain abscesses and in the areas of fungal
      pyelonephritis in the kidney. This finding is important for an understanding of
      the pathogenesis of fungal infections and may contribute to an analysis of the
      mechanisms of angiogenesis.

PMID- 7523303
TI  - Salmonella typhimurium invasion of epithelial cells: role of induced host cell
      tyrosine protein phosphorylation.
AB  - Salmonella typhimurium invades nonphagocytic epithelial and fibroblast cells via
      a process resembling phagocytosis. We have compared some phenotypes that are
      involved in S. typhimurium invasion by using different host cell lines, including
      HeLa, Henle-407, and A431. Infection with either wild-type S. typhimurium,
      bacterial culture supernatant, or the noninvasive invA mutant was associated with
      induction of tyrosine phosphorylation of host cell mitogenic activating protein
      kinase. However, we did not detect induction of tyrosine phosphorylation of the
      epidermal growth factor receptor in S. typhimurium-infected cells. Treatment with
      the tyrosine protein kinase inhibitor genistein did not reduce S. typhimurium
      invasion into any of these cell lines. These results suggest that S. typhimurium
      invasion is independent of host cell epidermal growth factor receptor activation.

PMID- 7523304
TI  - Some structures and processes of human epithelial cells involved in uptake of
      enterohemorrhagic Escherichia coli O157:H7 strains.
AB  - Several enterohemorrhagic Escherichia coli (EHEC) strains of serotype O157:H7
      isolated from patients with hemorrhagic colitis, ischemic colitis, or hemolytic
      uremic syndrome were all found to be able to invade certain human epithelial cell
      lines in vitro. Their ability to gain entry into epithelial cells was compared
      with those of known invasive Shigella flexneri and Salmonella typhi strains and
      the noninvasive E. coli strain HB101 in invasion assays utilizing gentamicin to
      kill extracellular bacteria. All EHEC strains under investigation were
      efficiently internalized into T24 bladder and HCT-8 ileocecal cells. In striking
      contrast to shigellae, the same EHEC strains were not taken up into human
      embryonic intestinal INT407 cells or HEp-2 cells any more than the noninvasive E.
      coli strain HB101. The mechanism(s) of EHEC internalization was characterized by
      comparing the invasion efficiencies in the absence and presence of a variety of
      inhibitors acting on structures and processes of prokaryotic or eukaryotic cells.
      Also, wild-type, plasmid-containing EHEC strains were compared with their plasmid
      cured isogenic derivative strains to determine if plasmid genes affect invasion
      ability. Plasmid-cured EHEC invaded as well as wild-type EHEC, indicating that
      invasion ability is chromosomally encoded. Inhibition of bacterial protein
      synthesis by simultaneous addition of bacteria and chloramphenicol to the
      monolayer blocked EHEC uptake dramatically, suggesting the presence of an
      invasion protein(s) with a short half-life. Studies utilizing inhibitors which
      act on eukaryotic cells demonstrated a strong dependence on microfilaments in the
      process of uptake of all EHEC strains into both T24 and HCT-8 cells. In general,
      depolymerization of microtubules as well as inhibition of receptor-mediated
      endocytosis reduced the efficiency of EHEC invasion of T24 cells, whereas
      interference with endosome acidification reduced EHEC entry into only HCT-8
      cells. Taxol-induced stabilization of microtubules did not inhibit
      internalization into T24 cells or into the HCT-8 cell line. In marked contrast,
      the ability of S. typhi Ty2 to invade either cell line was inhibited only by
      depolymerization of microfilaments. In addition to the cell line specificity of
      EHEC invasion, not all EHEC strains displayed uniform behavior in the presence of
      inhibitors, suggesting the existence of variant uptake pathways in different
      strains. Most importantly, previous reports of the inability of EHEC to invade
      INT407 or HEp-2 cell lines support the currently held belief that EHEC strains
      are noninvasive.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523308
TI  - Prevalence of hepatitis C virus infection in the household contacts of patients
      with HCV-related chronic liver disease.
AB  - It is still controversial whether the familial environment plays a role in the
      diffusion of HCV infection. The aim of this study was to evaluate the prevalence
      of anti-HCV positivity in the household contacts of patients with HCV-related
      chronic hepatitis. Nearly all the household contacts of 113 subjects with anti
      HCV+ chronic hepatitis (100/113 spouses and 260/290 children) were investigated.
      Anti-HCV was determined by means of ELISA II and was confirmed by RIBA II. Anti
      HCV positivity was found in 27% of the spouses and in 1.9% of the children.
      Prevalence of anti-HCV positivity in spouses correlated positively with the
      duration of the marital status. Seventeen/32 (53.1%) of anti-HCV-positive
      subjects were found to have chronic hepatitis. This study indicates that
      intrafamilial diffusion of HCV infection is mostly accounted for by horizontal,
      in particular spouse to spouse, transmission and that spouse to spouse
      transmission of HCV infection correlates positively with the duration of marital
      status.

PMID- 7523306
TI  - Arginine-derived nitric oxide reduces fecal oocyst shedding in nude mice infected
      with Cryptosporidium parvum.
AB  - Dietary L-arginine (4%) significantly reduced fecal oocyst shedding in athymic
      nude mice chronically infected with Cryptosporidium parvum. This effect appeared
      to be due to an increase in host nitric oxide (NO) production as it was not
      observed in arginine-supplemented animals administered the NO synthase inhibitor,
      N-nitro-L-arginine methyl ester. N-Nitro-L-arginine methyl ester alone
      significantly increased fecal oocyst shedding in chronically infected animals. In
      in vitro assays, oocyst excystation and sporozoite viability were significantly
      reduced by the NO donors sodium nitroprusside and S-nitroso-L-acetyl
      penicillamine in a concentration-dependent manner. These data suggest that
      arginine-derived NO may reduce the parasite load in experimental
      cryptosporidiosis.

PMID- 7523310
TI  - Expression of neuronal src mRNA as a favorable marker and inverse correlation to
      N-myc gene amplification in human neuroblastomas.
AB  - Neuron-specific src mRNA, which is expressed in human brain tissue by alternative
      splicing, is associated with neural differentiation. Neuronal c-srcNI expression
      may be associated with the ability of neuroblastomas to mature; furthermore, c
      srcN2 mRNA is induced in chemically differentiated neuroblastoma cells in vitro.
      The prognosis of a patient with a neuroblastoma is strongly affected by the
      ability of the tumor to differentiate in vivo. In order to clarify the
      relationship between neuronal src mRNA expression and the clinical outcome of a
      neuroblastoma, we analyzed the expression of src mRNA in neuroblastoma tissues
      from 28 patients by SI-nuclease-protection assay. N-myc gene amplification was
      also examined by Southern blot hybridization. The clinical significance of
      neuronal src mRNA expression and its relevance to N-myc gene amplification was
      also investigated. A high ratio (more than 10%) of c-srcN2 mRNA expression was
      observed in all early-stage tumors and in advanced neuroblastomas with a
      favorable prognosis. In contrast, in advanced neuroblastomas with an aggressive
      clinical phenotype, c-srcN2 mRNA expression was found at a low ratio (below 10%).
      Genomic amplification of the N-myc gene and expression of c-srcN2 mRNAs were
      inversely correlated. When combined with other prognostic markers such as N-myc
      gene amplification, the expression of c-srcN2 mRNA may be a new biological marker
      to predict the prognosis of patients with neuroblastomas.

PMID- 7523307
TI  - Nitric oxide is involved in control of Trypanosoma cruzi-induced parasitemia and
      directly kills the parasite in vitro.
AB  - This study was carried out to determine the role of reactive nitrogen
      intermediates in Trypanosoma cruzi infection. In vitro, splenocytes obtained
      during the acute phase of infection produced elevated amounts of nitric oxide
      (NO) that were correlated with the resistance or susceptibility of the animals.
      In vivo, the levels of NO2- plus NO3- in plasma during the later phase of
      infection were higher in C57BL/6 mice than in BALBL/c mice. The treatment of
      infected C57BL/6 mice with inhibitors of NO synthase increased parasitemia and
      mortality. Finally, we found that the NO donor drug S-nitroso-acetyl
      penicillamine is able to kill trypomastigotes in vitro in the absence of any
      other cells, suggesting a direct NO-mediated killing of T. cruzi.

PMID- 7523311
TI  - Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified
      proteins in human renal-cell carcinoma.
AB  - To study the possible involvement of reactive oxygen species (ROS) in the tumor
      biology of human renal-cell carcinoma (RCC), we analyzed 35 cases of RCC for 2
      parameters of oxidative damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG), a mutation
      prone DNA-base-modified product, was measured by means of high-performance liquid
      chromatography (HPLC) with an electrochemical (EC) detector, and 4-hydroxy-2
      nonenal (HNE)-modified proteins were measured with a polyclonal antibody against
      HNE-modified proteins. A 54% higher content of 8-OHdG was found in RCC than in
      the corresponding non-tumorous kidney, suggesting that the DNA of RCC is more
      exposed to ROS than is the DNA of non-tumorous kidneys. Immunohistochemistry for
      HNE-modified proteins showed a distinct staining pattern of fine to coarse
      granularity in the cytoplasm of RCC (n = 15), implying that lipid peroxidation
      products are located in cytoplasmic organelles. These results suggest that RCC
      constitutionally elaborates more ROS than is produced by the non-tumorous parts
      of kidneys. No correlation was found between clinical stage, histology, age or
      sex and the 2 parameters examined.

PMID- 7523309
TI  - Concentrations of benzene in blood and S-phenylmercapturic and t,t-muconic acid
      in urine in car mechanics.
AB  - Different parameters of biological monitoring were applied to 26 benzene-exposed
      car mechanics. Twenty car mechanics worked in a work environment with probably
      high benzene exposures (exposed workers); six car mechanics primarily involved in
      work organization were classified as non-exposed. The maximum air benzene
      concentration at the work places of exposed mechanics was 13 mg/m3 (mean 2.6
      mg/m3). Elevated benzene exposure was associated with job tasks involving work on
      fuel injections, petrol tanks, cylinder blocks, gasoline pipes, fuel filters,
      fuel pumps and valves. The mean blood benzene level in the exposed workers was
      3.3 micrograms/l (range 0.7-13.6 micrograms/l). Phenol proved to be an inadequate
      monitoring parameter within the exposure ranges investigated. The muconic and S
      phenylmercapturic acid concentrations in urine showed a marked increase during
      the work shift. Both also showed significant correlations with benzene
      concentrations in air or in blood. The best correlations between the benzene air
      level and the mercapturic and muconic acid concentrations in urine were found at
      the end of the work shift (phenylmercapturic acid concentration: r = 0.81, P <
      0.0001; muconic acid concentration: r = 0.54, P < 0.05). In conclusion, the
      concentrations of benzene in blood and mercapturic and muconic acid in urine
      proved to be good parameters for monitoring benzene exposure at the workplace
      even at benzene air levels below the current exposure limits. Today working as a
      car mechanic seems to be one of the occupations typically associated with benzene
      exposure.

PMID- 7523312
TI  - Collagens, integrins and the mesenchymal drift in glioblastomas: a comparison of
      biopsy specimens, spheroid and early monolayer cultures.
AB  - To analyze the process of mesenchymal differentiation in vitro, we examined 5
      human glioblastomas as biopsy specimens, monolayer cultures and 3-dimensional
      fragment spheroid cultures for the immunohistochemical expression of
      extracellular matrix (ECM) components (collagen types I, III-VI, laminin) and
      integrin receptors (beta 1, beta 2, beta 3 and beta 4 chains). mRNA for type-I
      and type-IV collagen alpha I chains was quantified using reverse transcription
      polymerase chain reaction. In situ, glioma cells expressed beta 1, the common
      beta chain of most integrin ECM receptors, while ECM components were restricted
      to vascular elements. Early monolayer cultures showed a marked increase in ECM
      components (interstitial collagens more than basement membrane components), and
      coexpression of ECM components and glial fibrillary acidic protein (GFAP) by most
      cells. beta 2 and beta 3 integrins were upregulated in the primary cultures. In
      the fifth passages, GFAP-positive cells were decreased and collagen-expressing
      cells increased. The spheroids exhibited preserved GFAP staining, neoexpression
      of beta 4 integrin in some tumors, and variable ECM expression by glioma cells
      which was lower than that in monolayer cultures. ECM deposition usually commenced
      in central spheroid areas where the Ki-67 proliferation index was low. We
      conclude that different culture systems are characterized by distinct expression
      patterns for ECM components and receptors, and that mesenchymal features in
      cultured gliomas arise due to transdifferentiation of glioma cells.

PMID- 7523314
TI  - S-phase fraction after gating on epithelial cells predicts recurrence in node
      negative breast cancer.
AB  - We have compared the prediction of distant recurrence for S-phase fraction (SPF)
      and DNA-ploidy, as estimated by flow cytometry, on an epithelial cell population
      and an unselected cell population from 268 node-negative breast-cancer patients
      diagnosed between 1985 and 1988. The tumor tissue was mechanically disintegrated
      and divided for flow cytometric analysis using both gated cells containing
      cytokeratin 8 and 18 and ungated cells treated with a detergent-trypsin solution.
      The relationship to distant recurrence was investigated for flow cytometric data,
      tumor size and estrogen and progesterone receptor content in univariate and
      multivariate Cox's regression analysis. The regression analyses were performed on
      209 cases with S-phase fractions estimated by both methods. In 11 cases, DNA
      ploidy classification differed, reflecting increased sensitivity to minor
      aneuploid peaks but a decreased ability to separate peaks in the near-diploid
      region for the gated populations. When SPF were used in univariate analysis as a
      continuous parameter or the upper tertile was used as cut-off value, SPF from the
      cytokeratin-gated cell population were most closely associated with recurrence
      and contributed additional prognostic information to SPF from the unselected cell
      population in the multivariate analysis. Out of the following variables:tumor
      size, ER and PR status, SPF and DNA ploidy, only SPF from immunoselected cells
      contributed prognostic information in multivariate analysis. These results
      indicate that SPF from immunoselected cell populations improves the prediction of
      recurrence in node-negative breast cancer.

PMID- 7523313
TI  - Inhibition of tumorigenic potential and prostate-specific antigen expression in
      LNCaP human prostate cancer cell line by 13-cis-retinoic acid.
AB  - Prostate-specific antigen (PSA) is a member of the kallikrein family and has been
      an important biological marker for prostate cancer. The mechanisms regulating PSA
      expression in prostatic cancer cells are unclear. The present study was designed
      to elucidate the role of 13-cis-retinoic acid (RA) in regulation of PSA and the
      tumorigenic potential of the human prostate cancer cell line LNCaP. The growth
      regulation of LNCaP cells was examined by DNA synthesis and doubling time. The
      tumorigenic potential of prostate cancer cells was analyzed by soft agar colony
      forming assay, in vitro invasion assay, type IV collagenase assay and binding to
      extracellular matrix assay. The nuclear receptors for retinoic acid (RAR alpha, 
      beta, -gamma and RXR alpha, -beta, -gamma) as well as PSA mRNA were determined by
      Northern blot using specific oligonucleotide probes. Our results suggest that 13
      cis-RA significantly inhibits PSA secretion and expression both at the mRNA and
      protein levels compared with untreated cells. Electron microscopic studies
      suggest that after 13-cis-RA treatment, cells become more differentiated as they
      contain lumina, lined by plasma membrane and microvilli. Prostate cancer cell
      growth and tumorigenic potential after 13-cis-RA treatment was significantly
      decreased compared with controls. Nude mice tumorigenicity studies showed that 13
      cis-RA-treated cells produced significantly smaller tumors compared with
      untreated cell tumors. There was also a significant increase in the expression of
      RXRa mRNA after 13-cis-RA treatment compared with untreated cells.

PMID- 7523316
TI  - Suppressed expression of insulin-like growth factor binding protein-1 mRNA in the
      endometrium: a molecular mechanism associating endometrial cancer with its risk
      factors.
AB  - The insulin-like growth factor (IGF) system is thought to function as a mediator
      of steroid hormone actions in the endometrium. IGFs (IGF-I and IGF-II) are also
      potent mitogens in endometrial cancer. The biological actions of IGFs are
      modulated by specific binding proteins (IGFBP)--6 cloned and sequenced so far-
      which may either inhibit or enhance the effects of IGF at the cellular level. In
      the endometrium, IGFBP-1 gene expression is stimulated by progesterone and
      inhibited by insulin, while IGFBP-1 inhibits the mitogenic action of IGF-I. In
      this study, we used a quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR) to investigate IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5 and IGFBP-6
      gene expression in endometrial cancer tissues. Endometrial cancer tissue samples
      were collected from 20 women (aged 54-79 yrs) with stage I to II well
      differentiated endometrial adenocarcinoma. Samples of normal endometrium (n = 14)
      obtained from women undergoing tubal ligation in various phases of the menstrual
      cycle, and normal early-pregnancy endometrium (decidua) were studied for
      comparison. In endometrial cancer tissues, the IGFBP-1 mRNA was undetectable or
      minimally expressed when studied by RT-PCR. The mean (+ SD) levels of IGFBP-2 and
      IGFBP-4 and IGFBP-5 mRNAs in endometrial cancer tissues did not differ from those
      in normal endometrium, in which no cyclic variation was observed, suggesting that
      the genes encoding IGFBP-2, IGFBP-4 and IGFBP-5 are not hormonally regulated in
      the endometrium. The IGFBP-6 mRNA expression showed a significant cyclic
      variation in normal endometrium, with low levels in late-proliferative and early-
      to mid-secretory phases and high expression in late-secretory and early
      proliferative phases. In endometrial cancer tissues, the mean IGFBP-6 mRNA level
      was similar to that in cycling endometrium during the peri-ovulatory period. In
      summary, a continuous stimulation of the endometrial epithelial cells by IGFs
      with suppressed IGFBP-1 expression may lead to an imbalance in the IGF system of
      the endometrium and trigger an uncontrolled cell proliferation, ultimately
      resulting in malignant transformation.

PMID- 7523315
TI  - Expression of interleukin 2 receptors on human carcinoma cell lines and tumor
      growth inhibition by interleukin 2.
AB  - We have previously shown that human squamous cell carcinomas (SCC) express the
      interleukin 2 receptor (IL2R)-alpha and -beta chains, and that the ligand, IL2,
      directly inhibits growth of the tumor in vitro and in vivo in the tumor xenograft
      nude mice model. We now show that the alpha and beta chains of IL2R are expressed
      on a variety of human carcinoma cell lines and on normal human keratinocytes in
      early-stage cultures. While all carcinoma cells in a population expressed IL2R
      alpha and -beta proteins, in keratinocytes obtained from different normal donors,
      variable proportions of cells were positive, as measured by flow cytometry. The
      carcinoma lines and 2/5 keratinocyte lines studied were also found to contain
      transcripts for the IL2R-gamma chain detectable by combined reverse transcription
      PCR (RT-PCR) and hybridization with the specific cDNA probe. Incubation of the
      gastric (HR) or renal cell carcinoma (RCC) cell lines, but not of other IL2R+
      carcinoma cell lines or normal keratinocytes, in the presence of IL2 resulted in
      dose-dependent inhibition of tumor cell growth. Monoclonal antibodies (MAbs)
      specific for IL2R-beta chain completely reversed this growth inhibitory effect of
      IL2. The ligand, IL2, also down-regulated surface expression of its own receptor
      and of intercellular adhesion molecule-I (ICAM-I) or class I major
      histocompatibility complex (MHC) antigens on IL2R+ tumor cells. All carcinoma
      cells studied incubated in the presence of IL2 exhibited significantly increased
      sensitivity to growth-inhibitory effects of other cytokines such as interferon
      (IFN)-gamma, tumor necrosis factor (TNF)-alpha or transforming growth factor
      (TGF)-beta. IL2 inhibited growth of the HR cells by arresting a significant
      proportion of tumor cells in the G0/G1 phase of the cell cycle. Thus, IL2 can
      have direct effects on IL2R+ carcinoma cells, leading to changes in growth or to
      increases in sensitivity of tumor cells to cytostatic activities of other
      cytokines.

PMID- 7523317
TI  - Involvement of nitric oxide synthase in antiproliferative activity of
      macrophages: induction of the enzyme requires two different kinds of signal
      acting synergistically.
AB  - Activated rodent macrophages inhibit micro-organism and tumour cell growth
      through a high output of nitric oxide; generated by an isoform of nitric oxide
      synthase which is induced, for example, in murine macrophages, by concomitant
      stimulation with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). We
      show here that LPS could be replaced as a co-stimulant by the mycobacterial
      derivative muramyl dipeptide (MDP) in macrophages, and by interleukin-1 (IL-1) in
      EMT-6 adenocarcinoma cells. Moreover, our results indicate that nitric oxide
      synthase RNA synthesis required either simultaneous or sequential exposure to IFN
      gamma and MDP/IL-1; whereas exposure to MDP/IL-1 followed by exposure to IFN
      gamma was ineffective. Thus, two kinds of signal could be distinguished: IFN
      gamma on the one hand, acting first in an irreversible way, and LPS, MDP, IL-1 on
      the other hand, which seemed to be permanently required for continuous
      transcription of the nitric oxide synthase gene.

PMID- 7523318
TI  - Myeloid cell proliferation stimulated by Steel factor is pertussis toxin
      sensitive and enhanced by cholera toxin.
AB  - Effects of G-protein toxins on Steel factor (SLF) and granulocyte-macrophage
      colony stimulating factor (GM-CSF) stimulated proliferation of human factor
      dependent cell line, M07e, were evaluated. Pertussis toxin pretreatment
      suppressed GM-CSF- or Steel factor-induced proliferation by 54 +/- 8%; however,
      proliferation induced by the combination of GM-CSF plus Steel factor was
      suppressed to a much lesser extent (14 +/- 8%). Pretreatment of M07e cells with
      cholera toxin, suppressed GM-CSF- and GM-CSF plus Steel factor-stimulated
      proliferation by 57 +/- 6% and 79%, respectively, but increased the proliferative
      response to Steel factor alone by twofold. Similar effects of pertussis toxin and
      cholera toxin were observed on proliferation of normal myeloid progenitor cells
      from human umbilical cord blood. Pertussis toxin treatment of M07e cells for 4 h
      resulted in the ADP-ribosylation of 40-42 kDa protein band but did not
      significantly increase cyclic AMP levels. Cholera toxin pretreatment was
      associated with a 10-fold increase in intracellular cyclic AMP levels. These
      results implicate pertussis toxin sensitive pathways for both GM-CSF and Steel
      factor, but suggest that these pathways may not be required for synergistic
      proliferation stimulated by the combination. In addition, proliferation
      stimulated by GM-CSF, +/- Steel factor, is sensitive to cholera toxin
      pretreatment; whereas cholera toxin pretreatment enhanced proliferation
      stimulated by Steel factor, possibly via increased cyclic AMP. This suggests
      divergent signal transduction pathways for the two cytokines.

PMID- 7523319
TI  - Delta-9-tetrahydrocannabinol treatment results in a suppression of interleukin-2
      induced cellular activities in human and murine lymphocytes.
AB  - Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in
      marijuana, has been shown to suppress a variety of interleukin-2-(IL-2)-dependent
      cellular functions in both murine and human lymphocytes. These effects were
      examined in both human peripheral blood lymphocytes (hPBL) and the IL-2-dependent
      murine cytotoxic T-cell line CTLL-2. Interleukin-2-induced thymidine uptake and
      uridine uptake were suppressed in a dose related manner when cells were co
      incubated for 48 h with 100 U rhIL-2/ml and 1-10 micrograms THC/ml. Interleukin-2
      induced protein synthesis was also suppressed in a dose related manner over this
      THC concentration range, with the hPBL being more susceptible to the suppressive
      effect of THC than the CTLL-2 cells. Autoradiographic analysis of the synthesized
      proteins from hPBL cell lysates reveals a generalized suppression of all nascent
      proteins in THC-treated cultures. Human natural killer cell activity is only
      affected at the highest concentration tested (10 micrograms THC/ml) while
      lymphokine-(IL-2)-activated natural killer cell activity is affected throughout
      the range of 1-10 micrograms THC/ml. Together these results suggest that THC
      interferes with the IL-2:IL-2 receptor signaling cascade at one or possibly many
      points causing a decrease in IL-2-induced metabolic activity and cytolytic
      function.

PMID- 7523320
TI  - Absence of Merkel cells in lesional skin of vitiligo [corrected].
AB  - BACKGROUND: In vitiligo, other than loss of melanocytes and melanin pigment in
      the lesional skin, keratinocytes are also involved. Human fetal Merkel cells are
      now generally considered to be derived from the epidermis. To date, no
      observations on Merkel cells in lesional skin of active vitiligo have been
      reported. METHODS: Merkel cells were identified by indirect immunofluorescence
      microscopy using the monoclonal antibody TROMA 1. RESULTS: No TROMA 1-positive
      cells were observed in the vitiliginous skin lesions in any of the specimens
      examined, whereas normal numbers of these cells were seen in the adjacent
      pigmented skin. CONCLUSIONS: This finding suggests that the processes that lead
      to damage of keratinocytes in vitiligo also involve other keratin-expressing
      cells such as the Merkel cells.

PMID- 7523321
TI  - Placental site nodule: a clinicopathologic study of 38 cases.
AB  - This report describes the clinical, histological, and immunohistochemical
      features of 38 cases of placental site nodule (PSN), a recently described lesion
      of intermediate trophoblast (IT). The patients ranged in age from 20 to 47 years
      (mean, 31.1 years). PSNs were diagnosed in endometrial (30 cases), endocervical
      (seven cases), and both endometrial and endocervical specimens (one case). The
      majority of biopsies were prompted by an abnormal Pap smear (13 cases) or
      complaints of menorrhagia (21 cases). All PSNs were microscopically detected,
      lobulated nodules composed of acellular, hyalinized material admixed with IT.
      Mitotic activity was noted in seven cases. Immunohistochemically, the IT
      expressed human placental lactogen (hPL) in 78% of cases and human chorionic
      gonadotropin (hCG) in 42% of cases, but their expression was weak and focal in
      contrast to uniform, strong staining for placental alkaline phosphatase (PLAP)
      (100%), cytokeratins (96%), and epithelial membrane antigen (EMA) (84%). Type IV
      collagen outlined the IT and stained the extracellular material in the cellular
      areas. Vimentin-positive cells within the lesions were fewer in number and in a
      different distribution than those expressing PLAP, CK, and EMA. Two consecutive
      PSNs occurred in one patient, but no patient developed gestational trophoblastic
      disease or a significant gynecologic neoplasm.

PMID- 7523322
TI  - Oxyphilic Sertoli cell tumor of the ovary: a report of three cases, two in
      patients with the Peutz-Jeghers syndrome.
AB  - Three women, aged 19, 21, and 30 years, two with the Peutz-Jeghers syndrome
      (PJS), had unilateral ovarian tumors composed of Sertoli cells with abundant
      eosinophilic cytoplasm. Electron microscopical and immunohistochemical
      examinations in one case supported the diagnosis of a sex cord tumor. Two
      patients are well 3 and 20 months postoperatively; the third was well for 15
      years when recurrent tumor involving multiple intraabdominal sites was
      discovered. The occurrence of two of these tumors in patients with PJS and the
      known increased frequency of sex cord tumors in patients with this syndrome
      indicate an association. Sertoli cell tumor should be included in the
      differential diagnosis of oxyphilic ovarian tumors, particularly if there is a
      tubular pattern.

PMID- 7523325
TI  - Surgical treatment of adrenal metastasis following pulmonary resection for lung
      cancer: comparison of adrenalectomy with palliative therapy.
AB  - Although adrenal metastases from lung cancer are frequently detected during the
      late clinical stage or at autopsy, they are rarely surgically treated following
      pulmonary resection for lung cancer. We detected adrenal lesions as initial
      clinical recurrence in 9 (1%) of 904 patients who underwent pulmonary resection
      for lung cancer at our institute between 1980 and 1992. Adrenalectomy was
      performed in five who had developed unilateral adrenal metastasis. One underwent
      simultaneous operation for primary and metastatic lesions, and 4 underwent
      adrenal surgery following pulmonary resection. The adrenal tumor was removed via
      laparotomy in three patients, and via posterolateral non laparotomic approach in
      two. Co-metastatic lesions which were detected incidentally at operation included
      intestinal metastasis in two patients and regional lymph node metastasis in two;
      these were simultaneously resected. Following adrenalectomy, all these patients
      were treated with adjuvant chemotherapy or radiotherapy. Two patients have
      remained free of relapse for 40 and 26 months, respectively, after adrenal
      surgery, while three died of other distant metastases more than 9 months after
      adrenalectomy. In contrast, the four patients who received chemotherapy or
      radiation therapy died less than 6 months after palliative therapy. Thus, we
      consider that surgical treatment for adrenal metastases following pulmonary
      resection for lung cancer is effective in selected cases. The indications for
      adrenalectomy are presented in comparison with those for palliative therapy, and
      several difficulties in the surgical management of adrenal metastases are
      discussed.

PMID- 7523323
TI  - Immunoreactivity of a cytokeratin-related polypeptide from adult Schistosoma
      mansoni.
AB  - A saline extract (SE) derived from living adult Schistosoma mansoni confers high
      levels of resistance to challenge infection in mice and rabbits. We have carried
      out a number of experiments to analyse the composition of SE and to define the
      proteins that are rapidly released from the parasite. One of these proteins, with
      apparent molecular mass of 62 kDa, is recognized by polyclonal and monoclonal
      antibodies raised against high molecular mass cytokeratins from human epidermal
      cells. Immunocytochemical studies revealed a tegumental staining using the anti
      cytokeratin antibody. Moreover, sera from schistosomiasis patients, as well as
      those from animals immunized with SE, were able to recognize this 62 kDa
      polypeptide as shown by immunoblot assays. These results suggest the existence of
      cytokeratin-containing filaments in the schistosome.

PMID- 7523326
TI  - The effect of octreotide (SMS 201-995) on experimentally induced pancreatitis
      with 50% ethyl alcohol in rats.
AB  - Brattle-Boro type rats with average weight of 200 gms were used for the
      experiment. We established 5 groups with 10 rats in each. Group I was the control
      group, Group II pancreatic trauma group and Group III rats were the pancreatitis
      group induced by 50% alcohol. Groups IV and V were the groups in which Octreotide
      was injected in different time intervals after induction of pancreatitis by 50%
      alcohol. Amylase values were statistically significant between the control group
      in which Octreotide was injected in different time intervals after induction of
      pancreatitis by 50% alcohol. The amylase values were statistically significant
      between the control group and the experiments (t2 = 4.69 p < 0.001, t3 = 8.06 p <
      0.00001, t4 = 4.23 p < 0.002, t5 = 4.3 p < 0.002), and it was also significant
      between Group III and Groups II, IV, V (t2 = 9.62 p < 0.0001, t4 = 10.26 p <
      0.0001, t5 = 3.69 p < 0.005), but it was not found significant between Groups II
      and IV, V (t4 = 0.52 p < 0.6, t5 = 1.69 p < 0.1). Histopathologic examination of
      the trauma group showed congestion, minimal lymphomonocyte infiltration. Patchy
      necrosis and shrinkage of the acinar cells with ductal dilatation were seen in
      the SMS 201-995 injection groups which were more pronounced in Group V. As a
      conclusion SMS 201-995 is not effective to prevent the ongoing pathology of
      pancreatitis but the increasing values of amylase were limited on the level of
      simply induced traumatic pancreatitis. It may be useful in the suppression of the
      enzymatic production during the course of pancreatitis.

PMID- 7523324
TI  - Chemical synthesis and characterization of peptides and oligomeric proteins
      designed to form transmembrane ion channels.
AB  - A strategy for the synthesis of peptides and oligomeric proteins designed to form
      transmembrane ion channels is described. A folding motif that exhibits a
      functional ionic pore encompasses amphipathic alpha-helices organized as a four
      helix bundle around a central hydrophilic pore. The channel-forming activity of
      monomeric amphipathic peptides may be examined after reconstitution in lipid
      bilayers in which peptides self-assemble into conductive oligomers. The covalent
      attachment of channel-forming peptides to the lysine epsilon-amino groups of a
      template molecule (KKKPGKEKG) specifies oligomeric number and facilitates the
      study of ionic permeation and channel blockade. Here we describe detailed
      protocols for the total synthesis of peptides and template-assembled four-helix
      bundle proteins, exemplified with the sequence of M2 delta (EKM
      STAISVLLAQAVFLLLTSQR), considered involved in lining the pore of the nicotinic
      acetylcholine receptor channel. For comparison, the synthesis of a second four
      helix bundle, T4CaIVS3 with the sequence of predicted transmembrane segment S3
      (DPWNVFDFLIVIGSIIDVILSE) of the fourth repeat of the L-type voltage-gated calcium
      channel, is included. Peptides and proteins are synthesized step-wise by solid
      phase methods, purified by reversed-phase HPLC, and homogeneity ascertained by
      analytical HPLC, capillary zone electrophoresis, SDS/PAGE, amino acid analysis
      and sequencing. Optimization of synthetic procedures for hydrophobic molecules
      include reducing resin substitution to avoid steric hindrance and aggregation of
      the final product. Protocols for the preparation of the samples prior to HPLC
      purification as well as the conditions and columns required for successful
      purification are presented. The methods developed are generally applicable for
      the chemical synthesis, purification and characterization of amphipathic peptides
      and template directed helical bundle proteins.

PMID- 7523327
TI  - Localization of aquaporin CHIP in the human eye: implications in the pathogenesis
      of glaucoma and other disorders of ocular fluid balance.
AB  - PURPOSE: The existence of integral membrane proteins that serve as selective
      water channels has been postulated to explain the movement of water across plasma
      membranes. Aquaporin CHIP (channel-forming integral membrane protein of 28 kd) is
      the first such channel to be characterized and is abundant in human erythrocytes
      and a variety of secretory and absorptive epithelia of the rat. Because
      disturbances in the movement of water characterize several ocular diseases, the
      distribution of CHIP in the human eye was studied. METHODS: Affinity-purified
      antibodies against purified CHIP protein were used for the indirect
      immunofluorescence localization of CHIP in human eye structures. Labeling was
      confirmed by immunoblot analyses of membrane preparations from eye structures.
      RESULTS: CHIP immunolabeling was found in the corneal endothelium, the lens
      epithelium, the nonpigmented epithelium of the ciliary process, the iris
      epithelium, and the endothelium of the trabecular meshwork and the canal of
      Schlemm. CONCLUSIONS: The presence of CHIP water channels in the secretory and
      absorptive tissues of the human eye provides a mechanism for transcellular water
      movement and may be important for understanding diseases of the eye that involve
      excess or insufficient movement of ocular fluid such as glaucoma, cataracts, and
      Fuch's dystrophy. In addition, the existence of CHIP in the outflow pathways of
      the human eye provides a novel explanation for the movement of water out of the
      eye.

PMID- 7523328
TI  - Effect of gadopentetate dimeglumine on proton magnetization transfer in protein
      solutions and tissues at 0.1 Tesla.

PMID- 7523329
TI  - Role of spatial distribution in proton relaxation enhancement by particulate iron
      oxide.

PMID- 7523330
TI  - Paramagnetic dextrans as magnetic resonance blood pool tracers.

PMID- 7523331
TI  - PAb1614, a monoclonal antibody reactive with the tumor antigens of SV40, JC, BK,
      and polyoma virus, and other JC virus tumor antigen cross-reactive antibodies of
      the PAb1601-1636 panel.
AB  - PAb1614, an SV40-specific monoclonal antibody of the panel PAb1601-1636 reacts
      with large and small tumor antigens of SV40, BK and JC virus, and with polyoma
      virus large and middle tumor antigens, but not with the large tumor antigen of
      the lymphotropic papova virus. Using immunofluorescence and immunoblot
      competition assays and ELISA with synthetic peptides, it is shown that the
      epitope is represented by the SV40 tumor antigen undecapeptide, K39-E49. This
      peptide comprises the tumor antigen consensus sequence, H42-G47, of the polyoma
      viruses. However, the epitope of PAb1614 probably does not exactly coincide with
      this hexapeptide. This explains why some cross-reactions are less strong, or
      absent, as in the case of the lymphotropic papova virus. Further antibodies of
      the PAb1601-1636 panel that cross-react with the JC virus large tumor antigen are
      PAb1602, 1604, 1606, 1618, 1621, 1622, 1623, 1624, 1626, 1629, and 1633.

PMID- 7523332
TI  - Platelet aggregation and histamine release by immunological stimuli.
AB  - Platelet aggregation and histamine release were evaluated in normal and IgE
      pretreated human platelets exposed in vitro to IgE, anti-IgE and thrombin. The
      response of platelets from atopic donors directly stimulated with anti-IgE was
      also evaluated. Histamine release was measured by fluorimetric analysis of
      histamine content in platelets and in supernatants. The morphology of platelets
      exposed to immunological and non-immunological stimuli was recorded using an
      electron microscope. A detectable amount of histamine was measured in quiescent
      platelets. Their exposure to varying concentrations of thrombin produces a
      progressive aggregation which runs parallel to histamine release. The effects
      were significantly enhanced in platelets pretreated with IgE. Incubation of
      normal platelets with increasing concentrations of IgE myeloma protein, or with
      anti-human IgE antibody was ineffective on both aggregation and histamine
      release. However, incubation of platelets passively sensitized with IgE-myeloma
      protein with different concentrations of anti-human IgE antibody produces a
      concentration-dependent increase both in aggregation and histamine release. The
      same effects were obtained using platelets from atopic donors directly stimulated
      with anti-IgE. The electron microscopic pattern of platelet aggregation induced
      by thrombin was indistinguishable from that evoked by anti-IgE in IgE pretreated
      platelets. Loratadine, a non-sedative H1-receptor blocker, significantly abated
      platelet aggregation and histamine release induced by anti-IgE in IgE pretreated
      platelets.

PMID- 7523334
TI  - The G gamma:A gamma ratios in the fetal hemoglobin of newborns of the Man ethnic
      group and their gamma-globin gene arrangements.
AB  - The G gamma:A gamma ratios of Hb F were determined in 331 newborn babies of the
      Man ethnic group in Liaoning Province, P.R. China, using polyacrylamide gel
      electrophoresis; in 27 cases they were also determined by reversed phase high
      performance liquid chromatography. The results showed that a high G gamma value
      (> 80%) was present in four cases (1.21%) and low G gamma values (30-48%) in six
      cases (1.81%); not a single case with the A gamma T [A gamma 75(E19)Ile->Thr]
      chain was found. Gene mapping analysis demonstrated that two babies with high G
      gamma values had the -G gamma-G gamma-/-G gamma-A gamma- (0.60%), and two others
      the -G gamma-AG gamma-A gamma-/-G gamma-A gamma- (0.60%) arrangements. Two of the
      four babies with low G gamma values were identified as -A gamma-A gamma-/-G gamma
      A gamma- (0.60%) and the other two as -GA gamma-/-G gamma-A gamma- (0.60%). The
      genotype -A gamma-A gamma- has not been reported before in Chinese.

PMID- 7523333
TI  - Differential effects of dexamethasone on the thymus and spleen: alterations in
      programmed cell death, lymphocyte subsets and activation of T cells.
AB  - The kinetics of DEX-induced changes in lymphocytes from the thymus and spleen of
      normal mice were examined in relation to cell numbers, programmed cell death
      (PCD), in vitro proliferative response to anti-CD3 antibodies or Con-A, and
      changes in lymphocyte subsets by flow cytometry. The above aspects were examined
      at 48, 24, 18, and 3 h after a single intraperitoneal injection of DEX. Profound
      reduction of thymocyte numbers was noticed particularly at 48 (74-84%) and 24 (43
      55%) h after DEX administration. PCD of thymocytes was not detectable at 48 h,
      marginally detectable at 24 h, markedly evident at 18 h, and minimally detectable
      at 3 h pi of DEX. PCD in splenic lymphocytes of DEX-treated mice was not clearly
      evident at these time points. Thymocytes from mice exposed to DEX (48 or 24 h)
      proliferated vigorously when cultured in the presence of anti-CD3 or Con-A,
      thereby suggesting that the remaining thymocytes can transduce activation
      signals. In contrast, splenic lymphocytes from the same animals responded poorly
      to these stimulants. Flow cytometric studies revealed that there was a marked
      increase in number of thymocytes expressing CD3+ (4-6 fold) and alpha beta TCR+
      (2-7 fold) surface molecules. On the other hand, no major changes in CD3+ or
      alpha beta TCR+ cells were noticed in the spleen of DEX-treated mice. Although
      the total numbers of cells expressing heat stable antigen, M1/69, were not
      markedly altered after DEX treatment, the fluorescent intensity profile was
      modified. There were no remarkable changes in CD45RB+ cells in these mice. CD44+
      cells were not decreased in DEX-treated thymocytes or splenic lymphocytes. Our
      results suggest that DEX has differential effects on the thymus and the spleen.

PMID- 7523336
TI  - Immunocytochemical study of tyrosine hydroxylase and dopamine beta-hydroxylase
      immunoreactivities in the rat pancreas.
AB  - An immunohistochemical and immunoelectron microscopic study was used to
      demonstrate tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH)
      immunoreactivities in the rat pancreas. Small TH immunoreactive cells were found
      in close contact with large TH immunonegative ganglion cells among the exocrine
      glands and were occasionally found in some islets. Some of these TH
      immunoreactive cells were also DBH immunopositive. The immunoreaction product was
      seen diffusely in the cytoplasm and in the granule cores of TH immunoreactive
      cells. All intra-pancreatic ganglion cells were immunoreactive for DBH, but not
      for TH. The TH immunoreactive cells were identified as small intensely
      fluorescent (SIF) cells due to their localization and morphological
      characteristics and showed no insulin, glucagon, somatostatin or pancreatic
      polypeptide immunoreactivities. These results indicate that SIF cells may release
      dopamine or noradrenaline to adequate stimuli while the intra-pancreatic ganglion
      cells with only DBH may not synthesize catecholamines in a normal biosynthetic
      pathway. TH immunoreactive nerve bundles without varicosities and fibers with
      varicosities, associated or unassociated with blood vessels, were found in both
      the exocrine and endocrine pancreas. Close apposition of TH immunoreactive nerve
      fibers to the smooth muscle and endothelial cells of the blood vessels was
      observed. A close apposition between TH immunoreactive nerve fibers and exocrine
      acinar cells and islet endocrine cells was sometimes found in the pancreas. The
      immunoreaction product was seen diffusely in the axoplasm and in the granular
      vesicles of the immunoreactive nerve fibers. Since no TH immunoreactive ganglion
      cells were present in the rat pancreas, the present study suggests that
      noradrenergic nerve fibers in the pancreas may be extrinsic in origin, and may
      exert an effect on the regulation of blood flow and on the secretory activity of
      the acinar cells, duct cells and endocrine cells.

PMID- 7523335
TI  - Immunohistochemical studies of neurochemical markers in normal human buccal
      mucosa.
AB  - The content of various substances, such as regulatory peptides, hormones and
      structural proteins, was investigated in normal buccal mucosa using indirect
      immunofluorescence. Thin nerve fibres, which from a morphological point of view
      were most probably sensory, showed immunoreactivity for substance P (SP),
      calcitonin gene-related peptide (CGRP), neuropeptide K (NPK) and neurokinin A
      (NKA). Also galanin (GAL), gamma-melanocyte stimulating hormone (gamma-MSH) and
      somatostatin (SOM) stained thin fibres were found in the propria, which were,
      however, few in number and the gamma-MSH staining was weak. CGRP, vasoactive
      intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI) and
      neuropeptide Y (NPY) immunoreactive nerve fibres were observed in close
      connection to blood vessels. SOM positive cells with processes were found, mostly
      scattered, in the connective tissue. A population of cells within the epithelium
      also showed somatostatin immunoreactivity. Protein S-100 (S-100) stained distinct
      populations of cells at two separate locations. In the propria, cells with one or
      two slender processes were seen, being mostly single but sometimes forming
      groups. In the epithelium, dendritic cells with many processes with or without
      'spines' were observed, mainly located to the basal layer of the lamina
      epithelialis. Single nerve fibres and nerve bundles were also stained.
      Neurofilament (NF) positive fibres, singly and in bundles, as well as endorgan
      like structures were seen. Neuron-specific enolase (NSE) and protein gene product
      9.5 (PGP 9.5) both stained the same structures, namely single fibres, nerve
      bundles, nerves surrounding vessels and innervating muscles and glands (if
      present in the section), as well as Merkel cells. Also with these two markers
      endorgan-like structures were seen. No clear innervation of the epithelium could
      be observed with the markers used. No methionine-enkephalin (ENK) or
      synaptophysin (SYN) immunoreactive material was found.

PMID- 7523340
TI  - Serum prostate-specific antigen after radiation therapy for clinically localized
      prostate cancer: prognostic implications.
AB  - PURPOSE: Serum prostate-specific antigen (PSA) levels following definitive
      radiation for prostate cancer are increasingly recognized as the most sensitive
      means to monitor disease status. However, beyond general agreement that patients
      fare poorly when posttreatment PSA levels fail to normalize, many questions
      relative to postirradiation PSA remain unanswered. This study evaluates the
      potential prognostic value of postirradiation PSA in a large cohort of patients
      followed with serial PSA determinations. METHODS AND MATERIALS: We analyzed
      disease outcome in 427 patients with clinical stages T1 (122 men), T2 (147 men),
      T3 (152 men), and T4 (six men) prostate cancer receiving definitive external
      radiation as sole therapy and followed for times ranging from 9-73 months (median
      30 months) with a total of 2260 posttreatment PSA values. RESULTS: Excluding
      three patients who died due to intercurrent illness without a posttreatment PSA,
      postirradiation PSA fell in 416 of 424 men (98%). Prostate-specific antigen
      levels continued to fall for up to 12 months but there was no evidence of
      significant declines beyond that. The time to nadir PSA was: 3 months, 60
      patients; 6 months, 68 patients, 9 months 148 patients; 12 months, 144 patients.
      Time to nadir was not a significant determinant of outcome. Prostate-specific
      antigen levels at 3 and 6 months and the nadir level were individually highly
      correlated with outcome. In multivariate analyses of posttreatment values, only
      the nadir value was independently significant, with increasing relapse rates as
      its value was higher. It retained significance when pretreatment PSA level was
      included in the model. Nadir values ranged from undetectable (52 patients) to
      20.3 ng/ml with a median of 1.1 ng/ml. Nadir values down to 1 ng/ml were
      prognostic; below 1 ng/ml (182 patients) the nadir value no longer yielded
      prognostic information additional to that inherent in the pretreatment value.
      Only patients with nadir levels < 1 ng/ml fared well (5-year incidence of relapse
      or rising PSA 17%); however, if the pretreatment level exceeded 30 ng/ml, then
      even a nadir level < 1 ng/ml was associated with a 40% failure rate at 5 years.
      CONCLUSION: The nadir PSA value after radiation is a significant posttreatment
      determinant of outcome and was second only to the pretreatment value.
      Surprisingly low nadir values were prognostically significant. Only patients
      whose nadir falls below 1 ng/ml can be said to have achieved a biochemical
      complete remission. However, even such low nadir values do not portend durable
      disease control for patients with high pretreatment PSA levels.

PMID- 7523337
TI  - Reflection contrast microscopy within chrome-alum haematoxylin stained thick
      tissue-sections.
AB  - This paper introduces two innovations in reflection contrast microscopy (RCM):
      (1) an extended application for qualitative light microscopic investigations; and
      (2) a novel method for quantification in cytochemistry. (1) We found out that RCM
      cannot only be used for surface characterizations and in thin sections but also
      within thick tissue-sections. The use of the RCM technique is demonstrated on
      slides of the supraoptic nucleus (SON) of the rat stained with chrome-alum
      haematoxylin: Among all the stained structures only neurosecretory granules are
      found to cause reflections. The visualization of the neurosecretion and its
      distribution is more distinct and of sharper contrast than in bright field
      microscopy. (2) The improved differentiation allows the quantification of
      neurosecretion in tissue-sections by combining RCM with grey-scale image
      analysis.

PMID- 7523341
TI  - PSA confirmation of cure at 10 years of T1B, T2, N0, M0 prostate cancer patients
      treated in RTOG protocol 7706 with external beam irradiation.
AB  - PURPOSE: This study was done to correlate prostatic specific antigen values with
      clinical no evidence of disease status for 28 long-term survivors of external
      beam irradiation from Radiation Therapy Oncology Group Study #77-06, and confirm
      the clinical observation of cure. METHODS AND MATERIALS: One hundred and four
      patients in Radiation Therapy Oncology Group 77-06 with T1B T2 N0, M0 with
      pathologically known negative lymph node status, were previously shown to have a
      10 year actuarial outcome equal to radical prostatectomy patients. Of these 104,
      28 were 9-13 year survivors with clinically no evidence of disease by physical
      examination and imaging. RESULTS: Prostatic specific antigen was available or
      obtained in 17 patients, 15 of the 17 had prostatic specific antigen values of <
      3.5 ngm/%, while 11 had values of < 1.5 ngm/%. Depending on which level one
      selects, 88% or 65% of clinical no evidence of disease 9-13 year survivors have a
      normal or low prostatic specific antigen. CONCLUSION: Prostatic specific antigen
      adds to the accuracy of determining clinical long-term cure and shows that 65-88%
      of patients who are clinical no evidence of disease are "biochemical" cures as
      well. These correlation percentages are quite similar to the largest contemporary
      surgical series, and strongly support the concept and fact of cure of prostate
      cancer with radiation.

PMID- 7523339
TI  - Choice of fixation and denaturation for the triple labelling of intra-cytoplasmic
      antigen, bromodeoxyuridine and DNA. Application to bone marrow plasma cells.
AB  - A triple staining method of intra-cytoplasmic antigen, bromodeoxyuridine (BrdU),
      and DNA for fluorescence image analysis is described. Several kinds of fixation
      and DNA denaturation methods were tested to obtain a technique suitable for
      heterogeneous tissues. The model chosen was the analysis of plasma cells in bone
      marrow. The fluorochromes used were fluorescein isothiocyanate (FITC) for intra
      cytoplasmic antigens (light chain immunoglobulins), aminomethylcoumarin acetic
      acid (AMCA) for BrdU, and propidium iodide (PI) for DNA. The quality of the
      staining was analysed according to: (1) cell morphology with a good preservation
      of the chromatin structure, (2) intensity of light chains and of BrdU labelling,
      and (3) the quality of DNA staining judged from a DNA histogram. For most of the
      analysed tissues, fixation with methanol followed by 0.5% paraformaldehyde and
      denaturation by an NaOH concentration adapted to the tissue gave good results.
      However, in our model fixation by methanol, followed by methanol/acetic acid and
      denaturation of DNA by 0.03 N NaOH was the solely satisfactory technique. A good
      correlation (P < 0.001) was found with the plasma cell BrdU labelling index
      obtained with our reference immuno-enzymatic technique. Quantification of DNA
      content showed a satisfactory G1 peak coefficient of variation (CV) in diploid
      cells and a 4C to 2C ratio equal to 2. With this technique, the nuclear and
      cytoplasmic structures of both myeloid cells and plasma cells were well
      preserved, while their sensitivity to DNA denaturation was quite different.

PMID- 7523338
TI  - Tissue treatment for whole mount internal lectin staining in the nematodes
      Caenorhabditis elegans, Panagrolaimus superbus and Acrobeloides maximus.
AB  - Four different fixation schemes, using ten fluorescent-labelled lectins, were
      investigated for whole mount internal staining of three rhabditid nematodes:
      Caenorhabditis elegans, Panagrolaimus superbus and Acrobeloides maximus. Acetone
      only fixation was found to give strong and reproducible staining, which could be
      prevented either by periodate treatment of the organisms or by specific
      inhibitory sugars of the lectins under investigation. Whereas the use of either
      phosphate or TRIS buffers had no effect on the staining pattern or the
      fluorescence intensity, the incubation time as well as the incubation temperature
      affected the staining reaction. The best results were obtained upon overnight
      incubation at 4 degrees C: the lectin staining could be inhibited in all cases,
      except for the intestinal brush border of C. elegans by the lectin of Lens
      culinaris.

PMID- 7523342
TI  - Preoperative serum prostate-specific antigen and Gleason grade as predictors of
      pathologic stage in clinically organ confined prostate cancer: implications for
      the choice of primary treatment.
AB  - PURPOSE: Despite careful preoperative staging, approximately 50% of patients who
      undergo radical prostatectomy for clinical stage A2 (T1b-c) and B (T2) prostate
      cancer are found to have pathologic stage C (T3-4) or D (N1) disease. This study
      investigates whether preoperative serum prostate specific antigen (PSA) and
      Gleason grade predict pathologic stage among patients with clinically organ
      confined prostate cancer. METHODS: The records of all 63 patients who underwent
      attempted pelvic lymphadenectomy and radical prostatectomy for adenocarcinoma of
      the prostate at our institution in 1990-91 were retrospectively reviewed.
      RESULTS: Patients with a preoperative serum PSA of 12.5 ng/mL or greater had an
      81% incidence of pathologic upstaging to stage C (T3-4) or D (N1) compared with
      38% for patients with a PSA less than 12.5 (p = 0.0015). The incidence of various
      pathologic findings for prostate specific antigen > or = 12.5 vs. prostate
      specific antigen < 12.5 was as follows: seminal vesicle involvement 29% vs. 5% (p
      = 0.0186), lymph node metastases 24% vs. 0% (p = 0.0029), capsular penetration
      71% vs. 38% (p = 0.0424), and positive margins 47% vs. 36% (p = 0.56). None (0/3)
      of the patients with Gleason grade 4 or less were pathologically upstaged
      compared with 49% (24/49) of patients with grade 5-7 tumors (p = 0.15) and 82%
      (9/11) of patients with grade 8 or higher cancers (p = 0.0474, grade 5-7 vs. 8
      10). Within the group of patients with Gleason grade 5-7, a prostate specific
      antigen of 12.5 ng/mL or greater predicted an 79% rate of upstaging compared with
      37% for patients with prostate specific antigen less than 12.5 (p = 0.0098).
      CONCLUSION: Patients with clinical Stage A2 (T1b-c) or B (T2) prostate cancer who
      have Gleason grade 8-10 tumors and those patients with Gleason grade 5-7 tumors
      with a preoperative serum prostate specific antigen of 12.5 ng/mL or higher have
      a high incidence of pathologic upstaging. These patients should be preferentially
      treated with external beam radiation in most cases.

PMID- 7523343
TI  - Indications for and the significance of seminal vesicle irradiation during 3D
      conformal radiotherapy for localized prostate cancer.
AB  - PURPOSE: To evaluate the use of pretreatment prostate specific antigen, Gleason
      score, and clinical stage as predictors of the risk of seminal vesicle
      involvement in patients with clinically localized prostatic cancer, and to
      determine the impact of excluding the seminal vesicles on the dose received by
      surrounding normal tissues. METHODS AND MATERIALS: An empirically derived
      equation combining the preoperative prostate specific antigen and Gleason score
      was applied to 188 patients treated with radical prostatectomy, for whom
      pathologic evaluation of the seminal vesicles was available. High and low risk
      groups for seminal vesicle involvement were defined using this equation. The
      observed risks of seminal vesicle involvement was compared to the predicted risk
      using the preoperative prostate specific antigen, Gleason score or clinical stage
      alone or using the empirical equation. Dose-volume histograms for five patients
      treated using six-field conformal radiotherapy were compared including and
      excluding the seminal vesicles. RESULTS: Using the empirically derived equation,
      a low risk group of 109 patients was identified with a calculated risk of seminal
      vesicle involvement of < or = 13% and an observed incidence of 7.3%. Among the
      high risk group of 79 patients, which included all patients with a calculated
      risk > 13%, 37% had seminal vesicle involvement (p < 0.001 low vs. high risk).
      Twenty percent of the rectal volume received on average above 86% of the total
      dose for the five plans which included the seminal vesicles compared to 68% for
      the five plans excluding the seminal vesicles. The doses to 40% of the rectal
      volume were 64% and 37% if the seminal vesicles were included and excluded,
      respectively. The dose to the bladder and femoral heads was also decreased but to
      a lesser extent. CONCLUSION: The empirical formula predicts risk of seminal
      vesicle involvement with a higher degree of significance for a larger number of
      patients than either Gleason score, clinical stage, or prostate specific antigen
      alone. Based on an analysis of our first 100 patients treated with definitive
      conformal therapy alone, approximately 47% of those patients could have been
      treated excluding the seminal vesicles. Excluding the seminal vesicles may allow
      us to go to a higher total dose with less rectal toxicity.

PMID- 7523344
TI  - Influence of initial presentation on treatment outcome of clinically localized
      prostate cancer treated by definitive radiation therapy.
AB  - PURPOSE: The increasing proportion of early stage prostate cancer diagnosed by
      various early detection methods together with reports espousing watchful waiting
      as a management option raise the possibility that patients may be selected for
      surveillance according to their initial presentation. METHODS AND MATERIALS: The
      outcome for 427 men with clinical stages T1 to T4 localized prostate cancer
      treated with radiation therapy was evaluated according to their presentation:
      elevated prostate-specific antigen (PSA) level; abnormal digital rectal
      examination; or, urologic symptomatology. RESULTS: With a median follow-up of 30
      months, there were no significant differences in disease outcome according to
      initial presentation. The actuarial incidence of relapse at 5 years was: PSA
      detected (54 patients), 24%; digital rectal-detected (173 patients) 29%; and,
      symptom-detected (200 patients) 31% (p = 0.79). Likewise, there were no
      significant differences in the incidence of postradiation rising PSA profiles
      among the three groups. The actuarial incidence of relapse and/or rising PSA at 5
      years was: PSA-detected 35%; digital rectal-detected 42%; symptom-detected, 48%
      (p = 0.72). On the other hand, T-stage, Gleason grade, pretreatment PSA,
      pretreatment acid phosphatase, and transurethral resection in T3/T4 disease were
      each highly correlated with outcome. In multivariate proportional hazards
      regression pretreatment PSA (p = 0.0003), Gleason grade (p = 0.045), and
      transurethral resection in T3/T4 disease (p = 0.0562) correlated with outcome,
      but initial presentation did not (p = 0.25). CONCLUSION: The absence of a
      prognostic gradient, good to bad, from PSA-detected through digital rectal
      detected to symptom-detected cancer suggests that the initial presentation of
      patients with localized prostate cancer is not a valid basis for selecting
      watchful waiting vs. initial treatment.

PMID- 7523346
TI  - Inoperable recurrent rectal cancer: results of a prospective trial with radiation
      therapy and razoxane.
AB  - PURPOSE: The effect of the sensitizer razoxane was prospectively evaluated in
      recurrent rectal cancer. Endpoints of the study were mainly local response rates
      and survival. METHODS AND MATERIALS: From 1984 to 1990 razoxane was given
      together with radiation therapy to 40 patients with recurrent inoperable rectal
      cancer. Loco-regional relapses in the pelvis were isolated in 24 and associated
      with distant metastases in 16 patients. Special attention was given to the subset
      of 24 patients with isolated local recurrences. This group was compared with
      historical controls treated with radiotherapy alone. The dosage of razoxane was
      150 mg/m2 daily orally starting 5 days before the first irradiation. The drug was
      then given each radiation day until the end of treatment. The median radiation
      dose was 60 (40-62) Gy in the evaluable patients. The minimum follow-up was 32
      months and the median 72 months. RESULTS: The rates of complete plus partial
      responses were 57% and 54%, respectively, for recurrent patients without and with
      distant metastasis. The 23 evaluable patients with isolated local relapses had a
      median survival of 24 months (12-94+); all patients surviving at least 1 year.
      CONCLUSION: The combination of radiotherapy and razoxane may lead to better local
      control and improved median survival compared to our historical controls and
      literature reports where radiotherapy alone was used. The treatment is easy to
      administer and is associated with a moderate toxicity.

PMID- 7523347
TI  - Prostate-specific antigen: clinical versus pathological stage.

PMID- 7523349
TI  - Response to Dr. Cox et al.

PMID- 7523345
TI  - Short-term freedom from disease progression after I-125 prostate implantation.
AB  - PURPOSE: To evaluate short-term clinical and chemical disease progression
      following computed tomography (CT)-based transperineal I-125 prostate
      implantation. METHODS AND MATERIALS: Sixty-two patients with clinical Stage T1 or
      T2 prostatic carcinoma had outpatient, CT-based transperineal I-125 prostate
      implantation and have been followed for 6-55 months (median: 19 months). Fifty
      six patients had an elevated prostate specific antigen (PSA) before implantation
      (> 4.0 ng/mL). Twenty patients had well-differentiated tumors, 39 were moderately
      differentiated, 2 were poorly differentiated, and 1 was indeterminate. A total of
      32-73 mCi I-125 was implanted (median: 47 mCi). The prescribed minimum prostatic
      dose was 140-160 Gy, and the actual matched peripheral dose ranged from 109-258
      Gy (median: 160 Gy). Lymph node dissection or postimplantation prostatic biopsies
      were not routinely performed. RESULTS: Of 54 patients with an elevated PSA prior
      to implantation and no prior hormonal treatment, 96% returned to normal within 24
      months of treatment. In 85% of patients, the PSA fell below 2.0 ng/mL and in 74%
      of patients, the PSA value fell to below 1.0 ng/mL. Seven patients had disease
      progression, one of whom has an isolated, rising PSA. The actuarial rate of
      chemical (rising PSA) or clinical failure at 3 years following implantation was
      17%. Of 38 patients who were sexually potent prior to implantation, 81% remained
      potent at 3 years. Five patients developed radiation-induced rectal ulcerations,
      11-22 months following implantation. Three patients required a transurethral
      resection of the prostate for postimplant urinary symptoms. CONCLUSIONS: The
      short-term clinical and chemical freedom-from-progression rates following I-125
      implantation are comparable to that achieved with prostatectomy, with high
      preservation of sexual potency and moderate morbidity.

PMID- 7523348
TI  - Response to Porter and Fontanesi.

PMID- 7523350
TI  - Nomogram for predicting the risk of node involvement in prostate cancer, give
      pretreatment prostate-specific antigen and Gleason score.

PMID- 7523351
TI  - Synthetic oligonucleotides with certain palindromes stimulate interferon
      production of human peripheral blood lymphocytes in vitro.
AB  - We studied the ability of synthetic single-stranded 30-mer
      oligodeoxyribonucleotides (oligoDNAs) with three different kinds of hexamer
      palindromic sequence to induce interferon (IFN) production of human peripheral
      blood lymphocytes (PBL). When PBL was cultured with oligoDNA having a palindrome
      of AACGTT or GACGTC, IFN activity was detected by bioassay in the culture fluid
      after 8 h, and the amount of IFN reached the maximum after 18 h. IFN-alpha was
      predominantly produced, and small amounts of IFN-beta and IFN-gamma were also
      found. OligoDNA with the palindrome ACCGGT had no effect.

PMID- 7523352
TI  - Semi-quantitative analysis of DNA topoisomerase-I mRNA level using reverse
      transcription-polymerase chain reaction in cancer cell lines: its relation to
      cytotoxicity against camptothecin derivative.
AB  - Expression of DNA topoisomerase (Topo)-I-mRNA in various cancer cell lines was
      detected using the reverse transcription-polymerase chain reaction (RT-PCR)
      method. The cytoplasmic polyadenylated RNA isolated from cancer cell lines was
      reverse-transcribed and the complementary DNA was amplified by PCR primed with
      Topo-I specific primers. Fidelity of the amplified sequence was confirmed by
      restriction endonuclease digestion and Southern blot hybridization. The level of
      Topo-I mRNA was correlated positively with the cytotoxicity of a Topo-I
      inhibitor, a camptothecin derivative. This RT-PCR method may be applicable to the
      assessment of sensitivity of cells to Topo-I targeted drugs, especially when only
      small quantities of cell samples are available.

PMID- 7523353
TI  - Colocalisation of NADPH-diaphorase with nitric oxide synthase and vasoactive
      intestinal polypeptide in newborn pancreatic neurons.
AB  - Numerous NADPH-diaphorase positive neurons were localised in the pancreatic
      ganglia cultured from newborn guinea pigs. Most of these ganglia were found in
      the head region of the pancreas. A majority of the labelled neurons occurred in
      groups, although solitary neurons were also present. NADPH-diaphorase labelling
      was localised mainly in the cell cytoplasm and its processes, but not within the
      nucleus. There were more nitric oxide synthase (NOS)-immunoreactive neurons in
      culture as compared with those positive for NADPH-diaphorase. NADPH-diaphorase
      activity has been colocalised with NOS and vasoactive intestinal polypeptide
      (VIP) in a subset of neurons in culture. Colocalisation of NADPH-diaphorase with
      NOS and VIP in cultured neurons was not restricted to the cell body but also to
      the proximal and distal processes. Some of these labelled processes made contacts
      with exocrine acinar and endocrine cells. It is concluded that neuronal nitric
      oxide (NO) may be influencing the secretory roles of the pancreas, thereby
      participating in homeostasis.

PMID- 7523355
TI  - The mniopetals, new inhibitors of reverse transcriptases from a Mniopetalum
      species (basidiomycetes). II. Structure elucidation.
AB  - The structures of six new drimance sesquiterpenoids, mniopetals A-F, were
      elucidated by a combination of chemical and spectroscopic methods. The mniopetals
      are inhibitors of RNA-directed DNA-polymerases.

PMID- 7523356
TI  - Anionic sites in blood capillaries of the mouse cochlear duct.
AB  - The blood-cochlear barrier, which consists of the molecular size and ionic charge
      barriers, is known to play an important role in production and absorption of
      inner ear fluids. In this study, we employed poly-L-lysine colloidal gold
      conjugates (PL-CG) in combination with Lowicryl K4M resin to demonstrate anionic
      sites in blood capillaries of the cochlear duct. Male ICR mice weighing 30-40 g
      with a positive Preyer's reflex were used. The basement membranes of blood
      capillaries of the stria vascularis and the spiral ligament were successfully
      labeled with PL-CG pH 2.5. The luminal surface of capillaries in the stria
      vascularis and the spiral ligament intensely reacted with PL-CG pH 2.5. However,
      PL-CG pH 1.0 stained only the basement membrane of the spiral ligament.
      Predigestion with several glycosidases nearly eliminated PL-CG labeling. Anionic
      charge located on the luminal surface of the endothelial cell was mainly caused
      by the presence of sialic acid. On the contrary, anionic charge of the basement
      membrane was caused in a substantial degree by chondroitin and heparan sulfate
      rich glycosaminoglycans. We obtained histochemical evidence that blood
      capillaries of the stria vascularis differ from those of the spiral ligament.

PMID- 7523358
TI  - pH and temperature modulate norepinephrine-dependent changes in endothelial
      permeability.
AB  - To evaluate the role of pH and temperature in norepinephrine (NE)-mediated
      decreases in endothelial permeability, we studied bovine pulmonary arterial
      endothelial monolayers at pH values of 4-9 and at temperatures of 35-39 degrees
      C. Only extremes of pH-modulated endothelial permeability and temperature had no
      effect. Although both NE and 3-isobutyl-1-methylxanthine decreased endothelial
      permeability, their effects were diminished by low pH and high temperature. Fever
      and acidosis may contribute to the edema seen in septic shock by a novel
      mechanism: attenuation of the barrier-improving function of NE.

PMID- 7523354
TI  - Localisation of nitric oxide synthase and its colocalisation with vasoactive
      peptides in coronary and femoral arteries. An electron microscope study.
AB  - The localisation and colocalisation of neuronal isoform (type I) nitric oxide
      synthase, endothelin-1, arginine-vasopressin and substance P in endothelial cells
      of rat coronary and femoral arteries was investigated by pre-embedding and
      postembedding immunocytochemistry. Nitric oxide synthase appeared in a high
      proportion of endothelial cells of both arteries (about 89% in the femoral
      artery, examined with the preembedding avidin-biotin-peroxidase method, and in
      almost all cells of the coronary artery, examined with the postembedding
      immunogold technique). Double immunogold labelling in single cells demonstrated
      the colocalisation of nitric oxide synthase with endothelin-1, arginine
      vasopressin and substance P. The immunolabelling was mostly confined to the
      cytoplasmic matrix. It is suggested that nitric oxide synthase/nitric oxide and
      the peptides examined may be involved in local control of blood flow in coronary
      and femoral arteries.

PMID- 7523359
TI  - Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide
      synthase inhibition.
AB  - We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal
      of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep
      were continuously infused with Escherichia coli endotoxin [lipopolysaccharide
      (LPS), 10 ng.kg-1.min-1] for 48 h. The NO synthase inhibitor N omega-nitro-L
      arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to
      systemic organs were determined with the radioactive microsphere technique. LPS
      induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic
      vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME
      administration, 24 h after infusion of LPS had begun] L-NAME administration
      normalized cardiac index [6.1 +/- 0.5 at 4 h posttreatment, 6.1 +/- 0.5 l.min-1.m
      2 at -24 h (baseline)] and systemic vascular resistance index (1,333 +/- 105 at 4
      h posttreatment, 1,280 +/- 163 dyn.s.cm-5.m2 at -24 h) and reduced all regional
      blood flows to near-baseline levels for the remainder of the study period (24 h).
      O2 consumption was unaffected by treatment.

PMID- 7523357
TI  - Effect of daily replacement therapy with recombinant bovine somatotropin on
      somatotropin, insulin-like growth factor I, and onset of puberty in beef heifers
      immunized against growth hormone-releasing factor.
AB  - Two experiments examined whether replacement therapy with recombinantly derived
      bovine somatotropin (rbST) would induce puberty in heifers that had been actively
      immunized at 6 mo of age against growth hormone-releasing factor (GRF). Heifers
      received daily i.m. injections of 25 mg of rbST (Exp. 1, n = 6; Exp. 2, n = 4) or
      vehicle (VEH; Exp. 1, n = 6; Exp. 2, n = 4) for 56 d. Serum concentrations of
      somatotropin (ST, nanograms/milliter) were low in all heifers before first
      injection in Exp. 1 (1.56 +/- .04) and 2 (.95 +/- .03). During treatment, serum
      ST was greater (P < .01) in rbST than in VEH heifers (75.4 +/- 4.8 vs 2.8 +/- .1
      ng/mL, respectively) in both experiments and remained increased through d 57
      (32.2 +/- 6.4 vs .90 +/- .01 ng/mL). IN Exp. 1 and 2, concentrations of serum IGF
      I were similar in rbST and VEH heifers before treatment, increased (P < .01) 12 h
      after first rbST, and remained increased (P < .01) through d 57 in rbST heifers.
      Concentrations of serum insulin (INS) and plasma glucose (GLU) were similar (P >
      .10) in rbST and VEH heifers before first injection (Exp. 1 and 2). Serum INS
      (micro-units/milliliter) was greater (P < .01) in rbST (61.7 +/- 3.7 and 36.0 +/-
      2.4) than in VEH (12.4 +/- 1.6 and 8.1 +/- 1.0) heifers on d 1 or 2 only, in Exp.
      1 and 2, respectively. In Exp. 1, GLU was increased (P < .05) by rbST on d 2
      through 57, but only on d 1 in Exp. 2. Proportion of heifers pubertal by d 21
      tended to be greater (P < .07) in rbST (3 of 6) than in VEH (0 of 5) heifers in
      Exp. 1, but not in Exp. 2 (1 of 4 vs 1 of 4, respectively). All heifers in Exp. 1
      and 50% of the heifers in Exp. 2 attained puberty by d 56. Daily rbST increased
      ST, IGF-I, INS, and GLU but did not hasten onset of puberty in heifers immunized
      against GRF.

PMID- 7523360
TI  - Mutations in the -10 TATAAT sequence of the gyrA promoter affect both promoter
      strength and sensitivity to DNA supercoiling.
AB  - Transcription of the gyrA and gyrB genes, which encode the subunits of DNA
      gyrase, increases in response to DNA relaxation. Previous studies have shown that
      a small segment of DNA extending from the -10 consensus hexamer to the start of
      transcription encodes the sequence determinants for this response. In this study,
      we examined the role of the -10 region in relaxation-stimulated transcription
      (RST). A synthetic derivative of the gyrA promoter was designed to allow the
      modular replacement of the -10 region, and mixed-oligonucleotide mutagenesis was
      used to obtain a collection of promoter mutants. Most substitutions result in a
      reduction of the promoter's RST response, and some mutations abolish it
      altogether. We also note that a variety of promoter changes can increase basal
      expression twofold above that seen for the gyrA promoter, despite sequences
      changes (up to three bases) which diverge from the consensus TATAAT of the wild
      type gyrA hexamer. The wild-type gyrA promoter, however, is the strongest
      promoter in this collection on a relaxed DNA template and appears to be repressed
      on a supercoiled template in vivo. Our results are consistent with a mechanism
      for RST that involves a step in transcription initiation.

PMID- 7523362
TI  - Treatment of clozapine-induced agranulocytosis with recombinant granulocyte
      colony-stimulating factor.
AB  - BACKGROUND: Is clozapine-induced agranulocytosis amenable to treatment with
      recombinant granulocyte colony-stimulating factor (rG-CSF)? Will this treatment
      provide benefits in terms of morbidity, mortality, and costs compared with
      current treatment? METHOD: Five patients with clozapine-induced agranulocytosis
      (granulocytes < 500/cu mm) were treated with the rG-CSF filgrastim, in addition
      to standard agranulocytosis therapy protocol. RESULTS: Time from onset until
      resolution of agranulocytosis was 8.2 +/- 2.1 days compared with a historical
      study of seven cases where filgrastim was not used and 15.7 +/- 3.7 days were
      required for resolution. CONCLUSION: rG-CSF (filgrastim) may be an effective and
      cost-reducing way to provide improved treatment for clozapine-induced
      agranulocytosis. More research is required.

PMID- 7523363
TI  - Archaic structure of the gene encoding transcription factor USF.
AB  - The upstream stimulatory factor (USF) is a helix-loop-helix transcription factor
      that interacts with specific sites on the DNA that are also recognized by the MYC
      oncoproteins. We isolated genomic clones to the murine 44-kDa form of USF (USF2
      gene). This unique gene spans 13 kilobases of DNA and is composed of 10 exons.
      The gene seems to have maintained its archaic structure, since many of the exons
      encode discrete functional domains of the transcription factor originally
      identified by protein sequence comparisons. A particularly striking HpaII tiny
      fragment island, extending over nearly 2,000 base pairs, surrounds the USF2
      translation initiation site. This region, which includes the USF2 promoter and
      the first four exons, is characterized by an overall GC content greater than 74%.
      Analysis by S1 mapping and transient transfection assays revealed that the USF2
      transcripts originate from an initiator element located within a highly GC-rich
      region that is surrounded by two long polyadenylate stretches and functions as a
      bidirectional promoter. Different forms of USF2 messages result from the presence
      or absence of the fourth exon in the processed USF2 mRNA. Alternative splicing
      correlates with the lack of a consensus lariat branch point in the third intron.
      Transient cotransfection assays revealed that the presence or absence of the
      amino acid sequences encoded by exon 4 affects considerably the transcription
      activation properties of the USF2 protein.

PMID- 7523364
TI  - The soluble form of E-selectin is an asymmetric monomer. Expression,
      purification, and characterization of the recombinant protein.
AB  - The gene coding for a soluble form of human E-selectin (sE-selectin) has been
      expressed in Chinese hamster ovary (CHO) cells. Cells seeded into a hollow fiber
      reactor secreted protein at a level of 160 mg/liter. The protein was purified to
      > 95% pure and low endotoxin (< 2 ng/mg), using physiological pH and buffers. The
      amino acid composition and N-terminal sequence were as predicted from the cDNA
      sequence. HL-60 cells bound to sE-selectin-coated plates in a dose-dependent
      manner, and this binding could be blocked up to 100% by pretreatment of HL60
      cells with sE-selectin. The concentration of sE-selectin required for 50%
      inhibition was 1 microM. This value puts an upper limit for the affinity of E
      selectin for its natural receptor. sE-selectin also inhibited inflammatory
      migration of neutrophils in a selective fashion. Purified sE-selectin exhibited a
      broad band of M(r) approximately 75,000 on nonreducing SDS-PAGE. sE-selectin
      eluted with M(r) approximately 310,000 from size exclusion chromatography at
      physiological pH and buffers, suggesting an oligomeric state. Matrix-assisted
      laser-desorption MS gave a molecular weight of 80,000, while the minimum monomer
      molecular weight from the gene sequence should be 58,571, demonstrating that the
      monomeric molecule thus expressed had 27% carbohydrate. Equilibrium analytical
      ultracentrifugation gave an average solution molecular weight of 81,600 (+/-
      4,500). Velocity ultracentrifugation gave a sedimentation coefficient of 4.3 S
      and, from this, an apparent axial ratio of 10.5:1, assuming a prolate ellipsoid
      of revolution. An analysis of the NMR NOESY spectra of sE-selectin, sialyl-Lewis
      X, and sE-selectin with sialyl-Lewis X demonstrates that the recombinant protein
      binds sialyl-Lewis X productively. Hence, in solution, sE-selectin is a
      functional elongated monomer.

PMID- 7523361
TI  - Nucleoid partitioning and the division plane in Escherichia coli.
AB  - Escherichia coli nucleoids were visualized after the DNA of OsO4-fixed but
      hydrated cells was stained with the fluorochrome DAPI (4',6-diamidino-2
      phenylindole dihydrochloride hydrate). In slowly growing cells, the nucleoids are
      rod shaped and seem to move along the major cell axis, whereas in rapidly
      growing, wider cells they consist of two- to four-lobed structures that often
      appear to advance along axes lying perpendicular or oblique to the major axis of
      the cell. To test the idea that the increase in cell diameter following
      nutritional shift-up is caused by the increased amount of DNA in the nucleoid,
      the cells were subjected to DNA synthesis inhibition. In the absence of DNA
      replication, the nucleoids continued to move in the growing filaments and were
      pulled apart into small domains along the length of the cell. When these cells
      were then transferred to a richer medium, their diameters increased, especially
      in the region enclosing the nucleoid. It thus appears that the nucleoid motive
      force does not depend on DNA synthesis and that cell diameter is determined not
      by the amount of DNA per chromosome but rather by the synthetic activity
      surrounding the nucleoid. Under the non-steady-state but balanced growth
      conditions induced by thymine limitation, nucleoids become separated into small
      lobules, often lying in asymmetric configurations along the cell periphery, and
      oblique and asymmetric division planes occur in more than half of the
      constricting cells. We suggest that such irregular DNA movement affects both the
      angle of the division plane and its position.

PMID- 7523365
TI  - Effect of transplantation of antibody heavy chain complementarity determining
      regions on ligand binding.
AB  - Active site structure-function analyses of anti-fluorescein single chain antibody
      4-4-20 and anti-single-stranded DNA single chain antibody 04-01 were conducted
      studying the ligand binding properties of hybrid antibodies resulting from
      systematic transplantation of heavy chain complementarity regions (HCDRs) from
      monoclonal antibody 4-4-20 into 04-01. Two prototype monoclonal antibodies were
      chosen because the primary structures of their respective light chains were
      nearly identical but the specificities and shape of their active sites were
      distinctly different. Based on nearly identical light chains, the diverse active
      site conformations (i.e. 4-4-20 pocket and 04-01 cleft) and subsequent
      specificities of the two antibodies were likely dictated by heavy chain
      properties. As a result, specificities of each HCDR transplant were analyzed in
      terms of binding reactivity with either fluorescein or (dT)8. Results of binding
      studies, together with idiotypic and secondary structure analyses, were used to
      determine the relative contribution of each HCDR to the active site conformations
      and ligand specificities of monoclonal antibodies 4-4-20 and 04-01. Collectively
      the various analyses led to the conclusion that the intradomain conformational
      dynamics and cooperativity necessary for the structural integrity of the low
      affinity cleft-shaped 04-01 anti-single-stranded DNA active site are probably
      less stringent than those of a high affinity pocket-shaped anti-fluorescein
      active site.

PMID- 7523366
TI  - Cell-free replication of the human papillomavirus DNA with homologous viral E1
      and E2 proteins and human cell extracts.
AB  - We have established the first homologous cell-free DNA replication system for a
      papillomavirus. The replication of the human papillomavirus type 11 (HPV-11)
      origin was achieved by using human 293 cell extracts supplemented with the HPV-11
      E1 and E2 proteins purified from insect cells infected with recombinant
      baculoviruses. Efficient replication depends on the HPV-11 origin, the HPV-11 E1
      and E2 proteins, as well as human DNA polymerase alpha, delta, replication
      protein A, topoisomerase I, and topoisomerase II. High concentrations of E1
      protein also promoted a low level of origin-independent replication which was
      suppressed by the addition of the E2 protein, whereas E2 protein stimulated
      origin-dependent replication. We also show that an intact E2 protein binding site
      was absolutely necessary for origin activity, as a strong HPV-11 origin was
      rendered inactive when one half-site of each of the three E2 binding sites was
      mutated. In contrast, there was only a relatively small reduction in this mutant
      origin activity when the cell extracts were supplemented with the bovine
      papillomavirus type 1 (BPV-1) proteins. These results suggest that the HPV-11 E2
      protein plays a primary role in HPV origin recognition. Furthermore, unlike
      transient replication in which HPV-11 and BPV-1 viral proteins promote efficient
      replication of homologous and heterologous origins, efficient cell-free
      replication took place only with the homologous combinations.

PMID- 7523367
TI  - Proteolysis-coupled secretion of the N terminus of apolipoprotein B.
      Characterization of a transient, translocation arrested intermediate.
AB  - We have shown that non-hepatic Chinese hamster ovary cells (CHO) have a specific
      inability to translocate and secrete apolipoprotein B (apoB), leading to its
      complete degradation in the endoplasmic reticulum (Thrift, R. N., Drisko, J.,
      Dueland, S., Trawick, J. D., and Davis, R. A. (1992) Proc. Natl. Acad. Sci.
      U.S.A. 89, 9161-9165). To gain an understanding why a protein having no
      predictable trans-membrane sequences can be stably integrated into the
      endoplasmic reticulum, we determined the topography and metabolic fate of apoB in
      both CHO cells and human hepatoma cells (HepG2). Using epitope-specific
      antibodies, we show that in microsomes from both cell types, apoB assumes a trans
      membrane orientation having 69 kDa of its N terminus in the lumen and the
      remaining portion of the C terminus residing on the cytoplasmic surface. In both
      cell types, proteolytic cleavage of the translocation arrested apoB by a process
      that can be blocked by acetyl-leucine, leucine, norleucal, produces an 85-kDa N
      terminal fragment that resumes translocation and is secreted. This same N
      terminal 85-kDa fragment is also found in human plasma. These results show that
      sequences residing outside of the membrane spanning domain can block
      translocation. Moreover, our data provide compelling evidence showing that apoB
      undergoes an unusual transient, translocation arrest, that serves as an entrance
      into the intracellular degradative pathway regulating its secretion.

PMID- 7523369
TI  - Misincorporation and mispaired primer extension by human immunodeficiency virus
      reverse transcriptase.
AB  - Pre-steady-state methods were used to study the fidelity of human
      immunodeficiency virus reverse transcriptase. Fidelity of DNA-directed DNA
      synthesis can be attributed to a 1-2 order of magnitude reduction in affinity for
      noncomplementary dNTPs, and a 1-4 order of magnitude reduction in the rate of the
      conformational change that limits the rate of nucleotide addition. Affinities of
      reverse transcriptase for paired or mispaired primer termini are similar.
      Discrimination against a mispaired primer is due to reduction in affinity for the
      next dNTP and reduction in rate of extension. Extension of mispaired termini
      proceeds 20-700-fold faster than the rate of dissociation of reverse
      transcriptase from the primer-template and is 2-3 orders of magnitude more
      frequent than nucleotide misincorporation. The rate-limiting step for extension
      of a mispaired terminus occurs at the conformational change or chemical step,
      depending on the nature of the mispair. Presence of a mismatch at the 3'
      penultimate position reduces pyrophosphorolysis of the primer by a factor of
      10(3), indicating that mispairs 5' to the site of chemistry can also affect
      catalysis.

PMID- 7523368
TI  - Conformational mimicry of a chlamydial neutralization epitope on filamentous
      phage.
AB  - Conformational constraints were imposed on a peptide epitope from Chlamydia
      trachomatis to improve its ability to elicit antibodies that cross-react with
      native antigen. Appropriate constraints were discovered by a strategy that
      required no prior knowledge of the epitope's native conformation. First, we
      constructed a library of 3.2 x 10(5) peptides in which the epitope's contact
      residues were subject to random conformational constraints, each constrained
      peptide being fused genetically to the surface of a filamentous phage vector.
      Next, we selected phage displaying the most native-like peptides in the library
      by affinity purification with antibodies that bind the epitope only in its native
      conformation. Finally, we immunized mice with the selected phage and titered the
      resulting antisera against both whole cells and unconstrained peptide. The ratio
      of anti-cell titer to anti-peptide titer, which reflects the channeling of the
      antibody response to the native epitope, was up to five times higher for affinity
      selected phage than for unselected peptide phage. In this case, therefore,
      "antigenic fitness," the ability of a peptide to bind antibodies specific for
      native epitope, correlated with "immunogenic fitness," its ability to elicit
      antibodies that are effective against the native antigen on an invading pathogen.
      If the correlation is general, surveying thousands or millions of peptides for
      antigenic fitness with phage display technology may be a simple but effective pre
      screen for immunogenic fitness, which is costly to assess directly.

PMID- 7523371
TI  - A motif in human histidyl-tRNA synthetase which is shared among several aminoacyl
      tRNA synthetases is a coiled-coil that is essential for enzymatic activity and
      contains the major autoantigenic epitope.
AB  - In myositis, disease-specific autoantibodies may be directed against an aminoacyl
      tRNA synthetase, usually histidyl-tRNA synthetase. To explore the basis for this
      phenomenon, we have made recombinant histidyl-tRNA synthetase in the baculovirus
      system. It was enzymatically active and recognized by human autoantibodies. A
      truncated protein lacking the first 60 amino acids was inactive as an antigen and
      as an enzyme. This region is within the first two exons, is predicted to have a
      coiled-coil configuration, and is found in some other synthetases but not in
      Escherichia coli or yeast histidyl-tRNA synthetase. Circular dichroism showed
      that the peptides from this region (amino acids 1-60 and 1-47) have the predicted
      high alpha-helical content, but smaller fragments (1-30, 14-45, and 31-60) do
      not. The peptides with a high alpha-helical content could inhibit autoantibodies
      almost completely, whereas the smaller peptides were unable to do so. The amino
      acid sequence of this coiled-coil domain in human histidyl-tRNA synthetase
      resembles the sequence of the extended this coiled-coil arm near the NH2 terminus
      of bacterial seryl-tRNA synthetase as well as similar regions in some eukaryotic
      aminoacyl-tRNA synthetases, raising the possibility that this domain serves a
      similar tRNA-stabilizing role and has been preserved from a common ancestor.

PMID- 7523370
TI  - Iron regulates cytoplasmic levels of a novel iron-responsive element-binding
      protein without aconitase activity.
AB  - Iron-responsive element-binding proteins (IRE-BPs) are cytosolic proteins that
      bind to a conserved RNA stem-loop, termed the iron-responsive element (IRE), that
      is located in the 5'- or 3'-untranslated regions of mRNAs involved in iron
      metabolism. Binding of the IRE-BP to 5'-IREs represses translation, whereas
      binding to 3'-IREs stabilizes the mRNA. The previously identified IRE-BP (BP1)
      contains a 4Fe-4S cluster and has sequence homology to mitochondrial aconitase.
      The 4Fe-4S cluster is important for iron-dependent regulation: BP1 containing
      iron has low affinity for the IRE and contains aconitase activity, whereas BP1
      lacking iron has high affinity for the IRE, but lacks aconitase activity. A
      second IRE-BP (BP2) has been identified in rat tissues and cells and exhibits
      many of the hallmarks of an IRE-BP, including binding to the IRE and functioning
      as a translational repressor of IRE-containing RNAs. BP1 and BP2 RNA binding
      activities are decreased in extracts from cells treated with iron, indicating
      that BP1 and BP2 are negatively regulated by iron. Although BP1 and BP2 share
      similar characteristics, they differ in two significant ways. Unlike BP1 levels,
      which do not change when RNA binding activity decreases in response to iron, BP2
      decreases to undetectable levels in extracts from cells treated with iron; and
      unlike BP1, BP2 does not have aconitase activity. These data indicate that BP1
      and BP2 are distinct proteins that have similar specificity for IRE binding and
      that function similarly in translation, but are regulated by iron via different
      mechanisms.

PMID- 7523373
TI  - Acute phase response factor and additional members of the interferon-stimulated
      gene factor 3 family integrate diverse signals from cytokines, interferons, and
      growth factors.
AB  - Cytokines and growth factors elicit responses in target cells through induction
      of gene expression. Signaling mechanisms leading to gene transcription from cell
      surface receptors often require tyrosine phosphorylation. A family of
      transcription factors comprising the interferon (IFN)-stimulated gene factor 3
      (ISGF3) multimeric complex are phosphorylated and activated in response to
      interferon. We describe a protein 50% identical to the 91-kDa subunit of ISGF3
      that constitutes the acute phase response factor (APRF). This protein was rapidly
      activated by interleukin-6 to bind an enhancer element common to genes activated
      in liver cells during the acute phase response to inflammation. Remarkably, APRF
      was also activated by IFN alpha, IFN gamma, epidermal growth factor, platelet
      derived growth factor, colony stimulating factor-1, and the cytokines leukemia
      inhibitory factor and oncostatin M. The growth factors also activated a third,
      distinct but related, DNA-binding protein in addition to APRF and p91. This novel
      factor or a closely related one, but neither APRF nor p91, was also activated in
      lymphoid cells by interleukin-2, erythropoietin, and interleukin-3. Activation of
      APRF, p91, and additional members of the ISGF3 family is thus a general feature
      of a wide variety of signaling pathways, integrating diverse signals through
      common transcriptional regulators.

PMID- 7523375
TI  - Inhibition of p21ras activation blocks proliferation but not differentiation of
      interleukin-3-dependent myeloid cells.
AB  - Interleukin-3 (IL-3) induces proliferation of immature myeloid cells and mast
      cells and prevents programmed cell death (apoptosis) in vitro. These activities
      are exerted through binding of IL-3 to specific, high affinity receptors that
      then initiate a series of intracellular signaling events. Among the earliest of
      these signaling events in an IL-3-dependent cell line such as 32Dcl3 are
      activation of one or more receptor-associated tyrosine kinases followed by
      activation of p21ras. In an effort to define the functional role of p21ras
      activation in mediating the effects of IL-3, we constructed a series of sublines
      of 32Dcl3 in which a dominant inhibitory mutant of Ha-ras (c-Ha-ras(Asn-17)) was
      expressed under the control of a steroid-inducible promoter. Steroid treatment
      (dexamethasone, 1 microM) specifically induced c-Ha-ras(Asn-17) protein and mRNA
      and blocked IL-3-induced accumulation of p21ras-GTP in 32Dcl3/p21rasN17 cell
      lines, but not in control cells. Dexamethasone slightly inhibited IL-3-dependent
      proliferation of control 32Dcl3 cell lines (to 80% of maximum), but it completely
      blocked proliferation of 32Dcl3/p21rasN17 cell lines and induced cell cycle
      arrest in G0/G1. This proliferative block could be overcome by cotransfection
      with v-ras, and was reversible if dexamethasone was washed out. Cells arrested by
      c-Ha-ras(Asn-17) were viable in culture for > 2 weeks, despite their inability to
      proliferate. Notably, however, these cells remained dependent on IL-3 for
      viability and initiated apoptosis within 18 h of IL-3 deprivation. Finally,
      granulocyte colony-stimulating factor-induced differentiation of 32Dcl3/p21rasN17
      cells to neutrophils was not affected by steroid-induced expression of c-Ha
      ras(Asn-17) and did not require removal of IL-3. These results suggest that IL-3
      induced proliferation and maintenance of cell viability are either initiated
      through separate signal transduction pathways or require different degrees of
      p21ras activation. Similarly, granulocyte colony-stimulating factor-induced
      neutrophil differentiation is not blocked by expression of c-Ha-ras(Asn-17).

PMID- 7523372
TI  - Activation of nuclear factor kappa B and oncogene expression by 12(R)
      hydroxyeicosatrienoic acid, an angiogenic factor in microvessel endothelial
      cells.
AB  - 12(R)-Hydroxy-5,8,14(Z,Z,Z)-eicosatrienoic acid (12(R)-HETrE) is an arachidonic
      acid metabolite formed by the corneal epithelium of several species, porcine
      leukocytes, and human and rat epidermal cells. It is a potent, stereospecific
      proinflammatory and angiogenic factor and its synthesis is increased manyfold in
      inflamed tissues, e.g. cornea and skin. It is possible that the angiogenic
      activity of 12(R)-HETrE is due to a direct mitogenic effect on microvessel
      endothelial cells via yet to be elucidated cellular and molecular mechanisms. In
      the present study, we demonstrated the ability of 12(R)-HETrE to stimulate the
      growth of quiescent endothelial cells in a time- and concentration-dependent
      manner with a maximal effect at 0.1 nM. This effect was highly stereospecific
      since its enantiomer, 12(S)-HETrE, had no effect within the same concentration
      range. Northern blot analysis and transient transfection experiments with
      chloramphenicol acetyltransferase constructs of oncogene promoter regions
      demonstrated significant increases over control (0.5% fetal calf serum) in c-myc
      , c-jun, and c-fos mRNA levels and expression in cells treated with 0.1 nM 12(R)
      HETrE. Electrophoretic mobility shift assay of nuclear protein extracts from
      cells treated with 12(R)-HETrE with specific radiolabeled oligonucleotides
      corresponding to known transcriptional binding sites, including AP-1, AP-2, SP1,
      TRE, NF kappa B, TFIID, OKT1, CREB, CTF/NF1, and GRE demonstrated a markedly
      rapid and specific increase in the binding activity of NF kappa B and to a lesser
      extent, AP-1. No significant increase was observed in the binding of other
      transcription factors assayed as compared to control (untreated) cells. Since the
      protooncogenes (c-fos, c-jun, and c-myc) are immediate early response genes that
      are implicated in the process of cell proliferation and differentiation, and
      activation of certain transcription factors, in particular NF kappa B, is
      associated with the immediate response of the cell to an injury, we propose that
      12(R)HETrE's mitogenic and angiogenic activities are mediated, in part, via the
      activation of NF kappa B and expression of these protooncogenes.

PMID- 7523374
TI  - Type VI RNA is the major gamma-glutamyl transpeptidase RNA in the mouse small
      intestine.
AB  - Mouse gamma-glutamyl transpeptidase (gamma GT) is encoded by a single copy gene
      with at least five and probably six different promoters directing the
      transcription of six types of gamma GT RNAs. In mouse small intestine, only Type
      I, V, and VI gamma GT RNAs are detected, and ribonuclease protection assays
      reveal that Type VI represents more than 90% of gamma GT RNA. To investigate the
      structure of intestinal gamma GT RNA in greater detail, we cloned and sequenced
      mouse intestinal gamma GT cDNAs. Seven of eight informative clones were Type VI
      and consisted of Type VI unique exons, VIa and VIb (as described previously by
      us) (Rajagopalan, S., Wan, D.-F., Habib, G. M., Sepulveda, A. R., McLeod, M. R.,
      Lebovitz, R. M., and Lieberman, M. W. (1993) Proc. Natl. Acad. Sci. U.S.A. 90,
      6179-6183) as well as common 3' sequences. Exon VIb contains two alternative
      splice acceptors, one previously identified by us and the other 17 bases 5' of
      this site. Another clone contained a previously unidentified gamma GT mRNA
      designated as Type VII. Type VII consists of a unique 5' exon which is 315 base
      pairs upstream of the exon VIa splice donor site and is spliced to exon VIb.
      Regulation of gamma GT expression in the small intestine is complex and involves
      at least three previously described promoters, alternative splicing, and a
      previously undescribed exonic sequence (Type VII RNA) 5' of promoter VI.

PMID- 7523376
TI  - Characterization and chromosomal localization of the cornea-specific murine
      keratin gene Krt1.12.
AB  - Keratins are a group of water-insoluble proteins constituting paired acidic and
      basic keratin molecules that form 10-nm intermediate filaments in epithelial
      cells. Expression of the K3/K12 keratin pair characterizes the cornea-type
      differentiation. However, the mechanism that regulates this cornea-specific K12
      expression remains unknown. To provide a better understanding of the cornea
      specific expression, we have cloned the K12 cDNA (Liu, C.-Y., Zhu, G.,
      Westerhausen-Larson, A., Converse, R., Kao, C. W.-C., Sun, T.-T., and Kao, W. W.
      Y. (1993) Curr. Eye Res. 12, 963-974). In present studies, the murine K12 keratin
      gene (Krt1.12) was isolated and characterized. The murine Krt1.12 gene spans
      6,567 base pairs of genomic DNA, and the mRNA encoding K12 keratin is distributed
      into eight exons. Chromosome mapping reveals that murine Krt1.12 is located
      within the Krt1 complex of mouse chromosome 11. In addition to the production of
      authentic K12 mRNA, the Krt1.12 gene gives rise to several alternate poly(A)+
      RNAs by the use of alternative splicing in intron 2, an alternative promoter in
      intron 1, and/or both. Sequence analysis indicates that the transcripts derived
      from alternative splicing and/or the alternative promoter do not have a long open
      reading frame for keratin or keratin-like molecules. It is not known whether
      these alternate K12 poly(A)+ RNAs have any biological functions, e.g. regulation
      of K12 gene expression.

PMID- 7523379
TI  - The thumb subdomain of T7 RNA polymerase functions to stabilize the ternary
      complex during processive transcription.
AB  - To examine the function of the thumb subdomain in bacteriophage T7 RNA polymerase
      we constructed a set of deletion mutants within this subdomain. These mutants
      exhibited reduced processivity during the processive, but not the abortive, stage
      of transcription. Reduced processivity was found to be due primarily to an
      increase in the processive ternary complex dissociation rate (destabilization of
      the processive ternary complex). The destabilization of the ternary complex does
      not appear to be due to a decrease in the affinity of the polymerase for the
      nascent RNA. These observations support the proposal that the thumb subdomain
      functions to stabilize the processive ternary complex during the processive (but
      not the abortive) stage of transcription, probably by wrapping around the
      template to prevent polymerase dissociation.

PMID- 7523377
TI  - Endothelial nitric oxide synthase membrane targeting. Evidence against
      involvement of a specific myristate receptor.
AB  - The endothelial isoform of nitric oxide synthase (ec-NOS) is targeted to the
      particulate subcellular fraction by means of N-terminal myristoylation. However,
      the association of ecNOS with the particulate subcellular fraction appears to be
      dynamically regulated, in that agonist treatment of endothelial cells induces
      translocation of the enzyme from membrane to cytosol (Michel, T., Li, G., and
      Busconi, L. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 6252-6255). cDNA encoding
      wild-type and myristoylation-deficient mutant (myr-) ecNOS was transcribed and
      translated in vitro, and we found that the recombinant wild-type but not the myr-
      mutant protein undergoes myristoylation and is able to associate with biological
      membranes prepared from diverse cell sources. Treatment of these cell membranes
      with heat or with trypsin did not affect their ability subsequently to serve as
      acceptor membranes for the wild-type recombinant enzyme. The wild-type ecNOS, but
      not the myr- mutant, is able to form stable associations with phospholipid
      liposomes. We also explored the possibility that a polybasic domain within the
      ecNOS protein might serve as a secondary structural determinant for ecNOS
      membrane association and constructed truncation mutants that flank a polybasic
      domain present in the ecNOS. These truncation mutants, transcribed and translated
      in vitro or transfected into COS-7 cells, undergo myristoylation and are able to
      associate with biological membranes in a fashion indistinguishable from the wild
      type ecNOS. Taken together, these results indicate that ecNOS binding to
      biological membranes is dependent upon interactions of the N-terminal myristoyl
      moiety of ecNOS with lipid components of the membrane, and this association does
      not require a specific membrane protein functioning as a myristate receptor nor
      the presence of a polybasic domain within the ecNOS.

PMID- 7523378
TI  - Cysteine 184 of endothelial nitric oxide synthase is involved in heme
      coordination and catalytic activity.
AB  - Nitric oxide synthase catalyzes the formation of an important messenger molecule,
      nitric oxide (NO). It is a P450-type hemoprotein, containing a cysteine thiolate
      as its proximal heme ligand, but the exact cysteine residue involved in heme
      coordination has not been identified. To locate this specific cysteine, we
      altered three potential cysteine residues (Cys-99, Cys-184, and Cys-441) to
      alanine residues in human endothelial nitric oxide synthase (eNOS) by
      oligonucleotide-directed mutagenesis and expressed the wild-type and mutant eNOSs
      in COS-1 and the baculovirus expression system. Mutation of Cys-235 to alanine
      was included to serve as a control. Mutation of Cys-184 resulted in a complete
      loss of NOS catalytic activity and abrogation of the formation of carbon monoxide
      (CO)-heme ferrous complex, which was detected on CO difference spectra as a
      distinct peak centered on 444-446 nm, without reduction in the quantity of eNOS
      protein. Mutation of Cys-99 also resulted in a loss of catalytic activity but did
      not eliminate the 444-446 nm peak. C441A and C235A mutants displayed considerable
      NOS activity and retained the CO-heme peak on CO-ferrous difference spectra.
      These results indicate that the cysteine 184 of human eNOS is most likely the
      proximal heme ligand.

PMID- 7523380
TI  - On the linkage between RNA processing and RNA translatability.
AB  - The immunoglobulin mu heavy chain gene of mouse hybridoma cells is expressed in
      two forms, microseconds and microns, differing in their use of 3' exons. As for
      many other mammalian genes, mutations in the mu gene which prematurely terminate
      translation often have the effect of reducing the amount of these mu RNAs. To
      test the generality of this relationship, we selected mutant hybridoma cell lines
      defective in IgM production and searched both for translation termination
      mutations which do not reduce the amount of mu RNA as well as for mutants which
      show the more commonly observed reduction in mu RNA. As observed previously, the
      amount of microseconds RNA is normal in mutants terminating in the C mu 4 exon;
      by contrast the amount of microns RNA is reduced in these mutants, indicating
      that the effect of the mutation is influenced by some feature near the 3' end of
      the RNA. Mutations terminating translation in other C region exons have a graded
      effect on RNA content, ranging from 10% the normal level for termination in the C
      mu 3 exon down to 1% for termination in the C mu 2 exon. By contrast, a mutant
      cell line terminating in the leader exon contained 25% the normal amount of mu
      RNA, suggesting that translation past some point might be required to fully
      engage the RNA degradation process.

PMID- 7523381
TI  - The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in
      hematopoietic cells.
AB  - The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor, which
      is important for the normal development of hematopoietic cells, melanoblasts, and
      germ cells. Autophosphorylation of c-kit receptor on tyrosine creates binding
      sites for cellular src homology 2 (SH2)-containing signaling molecules. The
      discovery of phosphotyrosine phosphatases that contain SH2 domains suggests roles
      for these molecules in growth factor signaling pathways. We found that Syp, a
      phosphotyrosine phosphatase widely expressed in all the tissues in mammals,
      associates with c-kit receptor after activation with its ligand, steel factor, in
      the factor-dependent cell line, M07e. Both NH2-terminal and COOH-terminal SH2
      domains of Syp, made as glutathione S-transferase fusion proteins, were able to
      bind to the activated c-kit receptor in vitro. Furthermore, Syp became marginally
      phosphorylated on tyrosine upon c-kit receptor activation, and tyrosine
      phosphorylated Syp was found to be complexed with Grb2 in steel factor-stimulated
      M07e cells. Direct binding between Syp and Grb2 was also observed in vitro. Last,
      Ras and Raf interacts in vitro as a result of steel factor-stimulated Ras
      activation. These results suggest that Syp may be an important signaling
      component downstream of the c-kit receptor and involved in activation of the Ras
      signaling pathway in hematopoietic cells.

PMID- 7523382
TI  - Nitric oxide reduces early growth response-1 gene expression in rat lung
      macrophages treated with interferon-gamma and lipopolysaccharide.
AB  - Since early growth response-1 (Egr-1) is required for macrophage differentiation
      and nitric oxide (NO) is immunosuppressive, we hypothesized that NO would reduce
      Egr-1 expression in rat lung macrophages. The inflammatory stimuli interferon
      gamma and lipopolysaccharide induced an early, transient increase in Egr-1 mRNA
      (> 5-fold at 2 h) and a sustained, high level of inducible NO synthase mRNA (>
      100-fold from 4 to 24 h). The NO metabolites nitrite and nitrate rose > 10-fold
      in medium from stimulated versus unstimulated cells over 24 h. Concomitant with
      elevated nitrogen oxides, Egr-1 mRNA levels declined to 80% below unstimulated
      cells at 24 h. This decline was blocked by an inhibitor of NO production, NG
      monomethyl-L-arginine. Further, the NO donor S-nitroso-N-acetylpenicillamine
      inhibited Egr-1 expression in a dose-dependent manner, producing complete
      inhibition at 0.5 mM. The effect of S-nitroso-N-acetylpenicillamine was not due
      to reduced macrophage viability. We conclude that Egr-1 induction precedes
      inducible NO synthase induction in stimulated rat macrophages and that subsequent
      NO production reduces macrophage expression of Egr-1. We propose that this
      mechanism is used to regulate macrophage differentiation in human
      immunodeficiency virus infection and other inflammatory states.

PMID- 7523383
TI  - Resistance of HIV-1 reverse transcriptase against [2',5'-bis-O-(tert
      butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2''-dioxide)]
      (TSAO) derivatives is determined by the mutation Glu138-->Lys on the p51 subunit.
AB  - Determination of the three-dimensional structure of the human immunodeficiency
      virus type-1 (HIV-1) reverse transcriptase (RT) has indicated a totally different
      folding for the 51-kDa subunit (p51) than for the 66-kDa subunit (p66). The
      polymerase catalytic site is located on the p66 subunit. Moreover, the HIV-1
      specific RT inhibitors, also designated as the non-nucleoside RT inhibitors
      (NNRTIs), select for amino acid mutations that afford resistance to these
      compounds and are clustered in the palm domain of the HIV-1 RT p66 subunit. This
      pocket is located in the vicinity of, but clearly distinct from, the polymerase
      active site. However, for the NNRTIs that belong to the class of the [2',5'-bis-O
      (tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole- 2'',2''
      dioxide)] (TSAO) derivatives, the resistance mutation is located at position
      Glu138. On the p66 subunit, this amino acid is distant from the binding site of
      the HIV-1-specific RT inhibitors. When the TSAO-specific resistance mutation
      Glu138-->Lys was introduced solely in the p51 subunit of the RT p66/p51
      heterodimer, the enzyme proved completely resistant to TSAO-m3T but retained full
      sensitivity to TIBO R82150 and ddGTP. On the other hand, when the mutation was
      introduced only in the p66 subunit the enzyme remained equally sensitive to the
      inhibitory effects of TSAO-m3T, TIBO R82150, and ddGTP. Our data provide
      compelling evidence for a structural and functional role of the p51 subunit in
      the sensitivity and/or resistance of the enzyme to the NNRTIs.

PMID- 7523384
TI  - Ets-2 and c-Myb act independently in regulating expression of the hematopoietic
      stem cell antigen CD34.
AB  - CD34 is currently the only well defined human hematopoietic stem cell marker and
      is expressed on 1-4% of normal bone marrow cells. Putative binding sites for Ets
      proteins, a family of transcription factors involved in the regulation of cell
      differentiation and proliferation in many cell systems, are present in the 5'
      flanking region of the CD34 gene. Some of these sites are in close proximity to
      binding sequences of the encoded product of the proto-oncogene c-myb, which
      regulates CD34 expression by interacting with the Myb binding sites. Here we
      demonstrate that Ets-2 (i) transactivates the CD34 promoter in rodent fibroblasts
      upon interaction with Ets binding sites and (ii) induces expression of CD34 mRNA
      and protein in the CD34- human glioblastoma T98G cells. Ets-2 and c-Myb
      transactivate the CD34 promoter independently because specific transactivation is
      abrogated by site-specific mutations of the binding sites or by competition with
      oligomers that include wild type but not mutated Myb or Ets binding sites. Ets-2
      and c-Myb appear to have addictive effects on transactivation of the CD34
      promoter and on induction of CD34 mRNA. Instead, CD34 surface protein levels
      might be induced synergistically, raising the possibility of a posttranslational
      mechanism of CD34 expression in cells constitutively expressing c-Myb and Ets-2.

PMID- 7523386
TI  - ATP-induced unspecific channel in yeast mitochondria.
AB  - ATP induced swelling of isolated yeast mitochondria suspended in an isoosmotic
      solution of potassium gluconate. Valinomycin stimulated the swelling rate,
      indicating that K+ influx in the presence of ATP is rate-controlling. This
      swelling was inhibited by ADP, phosphate (probably acting on the external face of
      the inner membrane), and Mg2+, which forms a complex with ATP. ATP-induced
      swelling did not require working F0-F1-ATPase since it was not inhibited by
      oligomycin and uncoupler. CTP and GTP also induced a swelling. ATP also induced
      mitochondrial swelling in potassium glutamate, chloride, and acetate but not in
      phosphate solutions. Sodium, but not ammonium, can replace potassium ion. It is
      probable that the ATP-channel opening also necessitates an electrogenic cation
      influx. Respiration also induced swelling of mitochondria suspended in isoosmotic
      potassium gluconate solution. ATP- or respiration-induced swelling were inhibited
      equally by N,N'-dicyclohexylcarbodiimide, propranolol, and Zn2+ but not by
      quinine; all these drugs inhibit the H+/K+ exchange. It was concluded that this
      unspecific channel is not open under conditions used to measure oxidative
      phosphorylation. Its physiological role remains unknown.

PMID- 7523385
TI  - A novel Gs alpha mutant in a patient with Albright hereditary osteodystrophy
      uncouples cell surface receptors from adenylyl cyclase.
AB  - Albright hereditary osteodystrophy (AHO) is an autosomal-dominant disorder
      characterized by decreased expression of Gs alpha and widespread tissue
      resistance to hormones that activate adenylyl cyclase. We identified a single
      mutation, R385H, in the Gs alpha gene of a subject with AHO who had evidence for
      a dysfunctional Gs alpha protein. The R385H substitution is near the carboxyl
      terminus of the Gs alpha protein and is located five amino acids upstream of the
      R389P mutation that uncouples Gs alpha from cell surface receptors in the unc
      clone of S49 murine lymphoma. To test the biological activity of the R385H
      mutant, we transiently expressed wild type, R385H, and R389P Gs alpha cDNAs in
      COS-1 cells. Neither of the mutant Gs alpha proteins stimulated adenylyl cyclase
      in response to l-isoproterenol (1 to 30 microM). By contrast, both mutant Gs
      alpha proteins showed activation of adenylyl cyclase in response to forskolin (10
      microM) and fluoroaluminate (10 mM). We propose that the R385H mutation produces
      a Gs alpha molecule that is unable to interact with hormone receptors and results
      in uncoupling of adenylyl cyclase from cell surface receptors. This uncoupling
      mutation represents a new type of molecular defect that can result in AHO.

PMID- 7523387
TI  - Platelet factor 4 stimulates thrombomodulin protein C-activating cofactor
      activity. A structure-function analysis.
AB  - Thrombomodulin (TM) is an anionic (pI approximately 4) protein cofactor that
      promotes thrombin (THR) cleavage of protein C to generate activated protein C
      (APC), a potent anticoagulant. We find that the cationic platelet alpha-granule
      protein platelet factor 4 (PF4) stimulates 4-25-fold the cofactor activity of
      rabbit TM and two differentially glycanated versions of an extracellular domain
      human TM polypeptide in which the glycosaminoglycan (GAG) is either present (GAG+
      TM) or absent (GAG- TM) with an ED50 of 3.3-10 micrograms/ml. No such stimulation
      occurs in response to beta-thromboglobulin or thrombospondin, or when protein C
      lacking its gamma-carboxyglutamic acid (Gla) domain is the substrate. Heparin and
      chondroitin sulfates A and E reverse PF4 stimulation. PF4 minimally affects the
      Kd for THR but decreases 30-fold (from 8.3 to 0.3 microM) the Km for protein C of
      APC generation by GAG+ TM. PF4 also strikingly transforms the [Ca2+] dependence
      profile of rabbit and GAG+ TM to resemble that of GAG- TM. A potential
      explanation for this is that PF4, like Ca2+, induces heparin-reversible
      alterations in native (but not Gla-domainless) protein C conformation as assessed
      by autofluorescence emission analysis. We conclude that PF4 stimulates TM APC
      generation by interacting electrostatically with both the TM GAG and the protein
      C Gla domain to enhance markedly the affinity of the THR.TM complex for protein
      C. By this mechanism, PF4 may play a previously unsuspected role in the
      physiologic regulation of clotting.

PMID- 7523389
TI  - The glucocorticoid receptor functions at multiple steps during transcription
      initiation by RNA polymerase II.
AB  - We have used a panel of monoclonal antibodies and a cell-free transcription assay
      to study the function of the tau 1 transactivation domain of the human
      glucocorticoid receptor. Three antibodies (monoclonal antibodies 250, 275, and
      286) specifically inhibited tau 1-dependent transcription, but had little or no
      effect on either basal transcription or the activity of an unrelated yeast
      transcription factor. This inhibition was not due to interference of DNA binding
      activity, as all three antibodies super shifted tau 1-containing protein-DNA
      complexes. Epitopes for all three antibodies were localized to a region between
      amino acids 190 and 200, which lies within the recently defined 41-amino acid
      core region of tau 1 that is required for transactivation (Dahlman-Wright, K.,
      Almlof, T., McEwan, I.J., Gustafsson, J-A., and Wright, A. P.H. (1994) Proc.
      Natl. Acad. Sci. U. S. A. 91, 1619-1623). In contrast to the effect on tau 1
      dependent transcription none of the antibodies tested antagonized the squelching
      ability of the tau 1 domain, suggesting that tau 1-mediated transactivation
      involves interactions in addition to those identified by the squelching assay.
      Consistent with this, a comparison of the kinetics of tau 1 squelching and
      inhibition of transactivation by monoclonal antibodies suggested a role for tau 1
      mediated transcriptional induction at two or more steps during transcription
      initiation by RNA polymerase II.

PMID- 7523388
TI  - Delayed "all-or-none" activation of inositol 1,4,5-trisphosphate-dependent
      calcium signaling in single rat hepatocytes.
AB  - When single rat hepatocytes were stimulated with the phospholipase C-activating
      hormone, vasopressin (from 300 pM to 1 microM), the [Ca2+]i signals were always
      "all-or-none" responses. At low concentrations of vasopressin, Ca2+ release was
      maximal because liberation of additional inositol 1,4,5-trisphosphate (IP3) by
      photolysis of its caged precursor at the top of the [Ca2+]i spike failed to
      increase [Ca2+]i further. However, if IP3 was generated by photolysis of caged
      IP3 in previously unstimulated cells, [Ca2+]i increased immediately, and the
      magnitude of the response was a graded function of the quantity of IP3 released.
      We also analyzed the kinetics of activation of intracellular IP3 receptor/Ca2+
      channels by monitoring the quench of sequestered dye by the entry of cytoplasmic
      Mn2+ into fura-2-loaded intracellular IP3-sensitive organelles. This Mn(2+)
      induced quench was precipitous and always preceded by a delay inversely related
      to the vasopressin concentration. In hepatocytes stimulated with 10 nM
      vasopressin, IP3 increased slowly, and the half-time of the IP3 rise was
      comparable with the latency for the release of intracellular calcium. The slow
      rise in IP3 would be predicted to produce accelerating Ca2+ release. This is
      consistent with the results of the Mn2+ quench experiments, which revealed
      accelerating activation of intracellular IP3-regulated calcium channels. We
      conclude that this accelerating release of Ca2+, which does not occur with
      instantaneous increases in IP3 due to flash photolysis, is likely to be important
      for generating the all-or-none Ca2+ mobilization that initiates the processes of
      intracellular [Ca2+]i oscillations.

PMID- 7523390
TI  - Intracellular turnover of cystic fibrosis transmembrane conductance regulator.
      Inefficient processing and rapid degradation of wild-type and mutant proteins.
AB  - Mutant (delta F508) and wild-type cystic fibrosis transmembrane conductance
      regulator (CFTR) were synthesized initially as an approximately 140-kDa core
      glycosylated precursor, which, in the case of wild-type CFTR, was chased to an
      approximately 160 kDa form bearing complex oligosaccharides. Mutant CFTR
      disappeared from the detergent-soluble cell extract with rapid (t1/2 = 27 min)
      kinetics. Only approximately 25% of the initially synthesized wild-type 140-kDa
      CFTR precursor was detected as mature protein; the remaining approximately 75%
      decayed with kinetics (t1/2 = 33 min) indistinguishable from those of the mutant.
      Rapid degradation kinetics and inefficient processing of wild-type CFTR were also
      observed in the colonic carcinoma lines HT29 and T84 and in stably transfected
      C127 cells, which express 5-50 times lower levels of CFTR. These results suggest
      that inefficient processing and rapid degradation of wild-type CFTR precursor are
      an intrinsic property of CFTR in these diverse cell types and are not an artifact
      of overexpression. Degradation of wild-type and mutant 140-kDa CFTR began without
      significant lag following synthesis. These data suggest that wild-type and delta
      F508 CFTR differ in the efficiency of folding of the core-glycosylated primary
      translation product.

PMID- 7523393
TI  - Phosphatase inhibitors block in vivo binding of peptides to class I major
      histocompatibility complex molecules.
AB  - Class I major histocompatibility complex (MHC) molecules are heterotrimers of
      heavy chains, beta 2-microglobulin, and 8-10 amino acid-long peptides. Assembly
      of class I MHC molecules into complexes which are stable and can be transported
      to the cell surface occurs soon after insertion of individual subunits into the
      endoplasmic reticulum (ER). To identify subcellular compartments required for
      class I MHC assembly, we studied class I biosynthesis in human cell lines treated
      with several inhibitors of intracellular transport. We found that HLA-B701
      molecules do not assemble in CIR transfectants in which a block in protein
      transport from the ER is established by treatment with phosphatase inhibitors. In
      contrast, stable HLA-B701 complexes form in cells in which the ER becomes mixed
      with the Golgi after treatment with brefeldin A. Neither treatment impaired
      binding of HLA-B701 to the ER-resident protein calnexin, and unassembled heavy
      chains in phosphatase-inhibited cells showed prolonged association with calnexin.
      In addition, the mouse class I molecule H-2Db, which binds beta 2-microglobulin
      in human T2 cells in the absence of transporter of antigenic peptides, formed
      complexes in CIR cell transfectants treated with phosphatase inhibitors. Taken
      together, these data demonstrate that phosphatase inhibitors do not prevent
      assembly of class I heavy chain beta 2-microglobulin dimers, but instead
      interfere with peptide loading. These results are consistent with the possibility
      that class I MHC molecules are transported from their initial site of insertion
      into the rough ER before binding peptides, or alternatively that peptide loading
      mediated by transporter of antigenic peptides is blocked by phosphatase
      inhibitors.

PMID- 7523395
TI  - In vitro and in vivo comparison of hammerhead, hairpin, and hepatitis delta virus
      self-processing ribozyme cassettes.
AB  - Ribozyme expression cassettes were constructed which generate trimmed, trans
      acting ribozymes from longer transcripts through the action of a downstream cis
      acting ribozyme. This self-processing system produces small, well-defined trans
      acting ribozymes with minimal, nonproductive, intramolecular structure. These
      cassettes also permit direct comparison of different ribozyme expression vectors
      without the need to compensate for different transcription initiation and
      termination sequences. Expression cassettes were created that contain a T7
      promoter and that encode a single trans-acting ribozyme followed by either a
      hammerhead, hairpin, or hepatitis delta virus cis-acting ribozyme. All three
      ribozyme motifs function efficiently when transcribed in vitro, although slight
      differences are observed in the efficiency of self-processing for the different
      motifs. When transiently expressed in cultured mouse cells, the same specific
      cleavage products are observed. In addition, the relative efficiencies of in
      vitro self-processing between the three ribozyme constructs was maintained in
      vivo. Thus, the cellular milieu does not differentially alter the activity of the
      three ribozyme motifs. Detection of ribozyme-catalyzed RNA cleavage products from
      cultured cells is direct proof of ribozyme action in vivo.

PMID- 7523391
TI  - Matrix metalloproteinases degrade insulin-like growth factor-binding protein-3 in
      dermal fibroblast cultures.
AB  - Insulin-like growth factor binding protein-3 (IG-FBP-3) is degraded by a Zn(2+)
      dependent protease(s) produced by human dermal fibroblasts in vitro (Fowlkes, J.
      (1994) Endocrine J. 2, 63-68). Initial studies using IG-FBP-3-substrate
      zymography identified several IGFBP-3-degrading proteases with M(r) 52,000
      72,000, which were inhibitable by EDTA and were shifted to lower M(r) species
      after treatment of conditioned medium with an organomercurial, suggesting that
      they might represent one or more of the matrix metalloproteinases (MMPs).
      Immunoblotting of conditioned medium demonstrated the presence of proMMP-1 (52
      and 55 kDa), proMMP-3 (58 and 60 kDa), and proMMP-2 (72 kDa) whose molecular
      masses corresponded identically to those of the IGFBP-3-degrading proteases.
      Degradation of recombinant human (rh) IGFBP-3 by conditioned media was blocked (>
      80% inhibition) by tissue inhibitor of metallo-proteinases-1, a specific
      inhibitor of all MMPs, while removal of MMPs -1, -2, and -3 from conditioned
      medium by sequential immunoaffinity and gelatin-Sepharose chromatography resulted
      in the complete loss of IGFBP-3-degrading proteinase activity. Furthermore, human
      MMP-1, MMP-3, and to a lesser extent MMP-2 degraded rhIGFBP-3 in vitro. Sequence
      analysis of rhIGFBP-3 cleavage sites produced by MMP-1, -2, or -3 demonstrated
      that each cleaved within the mid-region of the binding protein, a domain with
      little or no homology with the other five cloned IGFBPs. These studies suggest
      that MMPs, beyond their previously described functions as extracellular degrading
      enzymes, may also exert effects on cellular growth and proliferation via
      degradation of IGFBP-3, thus enhancing IGF bioavailability.

PMID- 7523394
TI  - Hydrolytic inactivation of a breast carcinoma cell-derived serpin by human
      stromelysin-3.
AB  - To elucidate structure-function relationships of stromelysin-3, a putative matrix
      metalloproteinase originally identified at the tumor-stromal cell interface in
      breast carcinomas, the human cDNA was expressed in mammalian cells, and its
      products were isolated and characterized. In stably transfected cells,
      stromelysin-3 was recovered as a complex mixture of species ranging in size from
      approximately 20 to 65 kDa. Among these products, a major 45-kDa species with an
      N terminus of Phe98 and an intact C-terminal domain was identified as a true
      endopeptidase on the basis of its ability to cleave the bait region of alpha 2
      macroglobulin between Phe684 and Tyr685, a site identical to that recognized by
      stromelysin-1. However, unlike stromelysin-1 or other members of the matrix
      metalloproteinase family, the mature form of stromelysin-3 was unable to
      hydrolyze a range of extracellular matrix molecules associated with either the
      basement membrane or interstitium. To probe for alternate substrates among tumor
      cell-derived products, purified stromelysin-3 was incubated with [35S]methionine
      labeled medium conditioned by the breast cancer cell line, MCF-7. Under these
      conditions, a single, tumor cell-derived protein was hydrolyzed as assessed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography.
      Following anion-exchange chromatography and preparative gel electrophoresis, the
      stromelysin-3 substrate was identified by N-terminal sequencing as the serine
      proteinase inhibitor, alpha 1-proteinase inhibitor. Further studies demonstrated
      that stromelysin-3 rapidly destroyed the antiproteolytic function of alpha 1
      proteinase inhibitor by cleaving the antiproteinase at a distinct site between
      Ala350 and Met351 within the reactive-site loop. Together, these data not only
      demonstrate that human stromelysin-3 acts as a powerful endopeptidase with a
      restricted substrate specificity distinct from all other matrix
      metalloproteinases, but also serve to identify serine proteinase inhibitors as
      potential physiologic targets at sites of extracellular matrix remodeling.

PMID- 7523392
TI  - Porins from plants. Molecular cloning and functional characterization of two new
      members of the porin family.
AB  - Porins are voltage-gated diffusion pores found in all eukaryotic kingdoms. Here
      we describe, for the first time, the identification and characterization of two
      cDNAs encoding porins from plants. Peptide sequences obtained from a 30-kDa
      protein of envelope membranes from pea root plastids allowed the isolation of two
      cDNA clones from pea and maize. On the protein level, both proteins are
      homologous by 58%. Sequence comparison against the Swiss-Prot sequence data base
      revealed a homology of about 25% to mitochondrial porins from fungi and human.
      Computer-aided predictions of the secondary structure of the plant porins
      revealed the presence of 16 antiparallel beta-strands that are also found in
      mitochondrial porins. Porins from non-green plastids and from the outer
      mitochondrial membrane were reconstituted into planar lipid bilayers. The
      proteins showed high pore-forming activities and similar single-channel
      conductances. In vitro translated porin was preferentially imported only into non
      green plastids but not into chloroplasts. To our knowledge, this is the first
      example of selective import of a plastid protein into different types of
      plastids. This finding is in line with the observation that an immunoreactive 30
      kDa band was only found in non-green plastids and mitochondria but not in
      chloroplasts. We conclude that mitochondria and non-green plastids possess
      homologous porin proteins, whereas chloroplasts are characterized by a different
      type of porin.

PMID- 7523396
TI  - Structure-specific cleavage of the RNA primer from Okazaki fragments by calf
      thymus RNase HI.
AB  - Cleavage specificity of RNase HI was examined on model Okazaki fragments, to
      determine the likely role of this nuclease in lagging strand DNA replication.
      Each substrate was prepared by annealing a short RNA primer, made by
      transcription in vitro, to a single-stranded synthetic DNA template, and
      subsequently extending the primer by DNA polymerization. The calf thymus RNase HI
      makes a structure-specific endonucleolytic cleavage in the RNA primer, releasing
      it intact, and leaving a mono-ribonucleotide at the 5' terminus of the RNA-DNA
      junction. This specific cleavage, one nucleotide upstream of the RNA-DNA
      junction, is RNA primer sequence- and length-independent. Cleavage specificity is
      lost if the RNA primer is not extended with DNA, or if the substrate has a nick
      at the RNA-DNA junction. In addition, the cleavage at a single site requires
      Mg2+. Cleavage in the presence of Mn2+ is less specific. Neither human
      immunodeficiency virus reverse transcriptase nor Escherichia coli RNases H
      perform such a structure-specific cleavage before an RNA-DNA junction. Our work
      indicates that calf RNase HI is designed to recognize Okazaki fragments. It has
      the specificity to remove their initiator RNA segments, except for one
      ribonucleotide, by a single endonucleolytic cleavage in vivo.

PMID- 7523397
TI  - The DNA cleavage pathway of iron bleomycin. Strand scission precedes deoxyribose
      3-phosphate bond cleavage.
AB  - DNA strand scission initiated by bleomycin is a multistep process. Three C-C or C
      O bonds are broken, releasing base propenal, a nucleic base derivative with
      deoxyribose carbons 1-3. Either C-3'-(phosphate-O) cleavage or C-3'-C-4' plus C
      1'-(ring-O) bond cleavages could cause strand cleavage. To determine the sequence
      of bond breakage, d(CAAGCTTG) duplex was examined for rates of 1) strand
      scission, monitored by the hyperchromicity of cleavage-induced denaturation; 2)
      base propenal formation, monitored by 1H NMR spectroscopy; 3) 5'-terminal
      phosphomonoester formation, monitored by 31P NMR spectroscopy. Strand scission
      occurred with t 1/2 = 4.1 +/- 0.5 min at 4 degrees C, faster than base propenal
      formation (t 1/2 = 6.7 +/- 0.3 min). Thus newly cleaved DNA includes a base
      propenal precursor (t 1/2 = 2-3 min). The 5'-phosphate terminus forms (t 1/2 =
      7.4 +/- 0.8 min) concurrently with base propenal. Since strand scission precedes
      phosphomonoester formation, strand scission cannot arise from C-3'-(phosphate-O)
      cleavage. Instead, the base propenal precursor must be linked to the future 5'
      phosphate terminus, with strand scission arising from a combination of C-3'-C-4'
      and C-1'-(ring-O) bond cleavages. These results provide experimental support for
      a recently proposed mechanism that accommodates an early oxygen attack at C-4'
      and 2'-deprotonation without requiring simultaneous strand scission and 5'
      phosphate terminus formation.

PMID- 7523399
TI  - Direct binding of collagen to the I domain of integrin alpha 2 beta 1 (VLA-2,
      CD49b/CD29) in a divalent cation-independent manner.
AB  - Integrin alpha 2 beta 1 is a major divalent cation-dependent receptor for
      collagen. Here, we show that the recombinant inserted/interactive domain (I
      domain) of alpha 2 specifically interacts with collagen, indicating the I domain
      contains all the components necessary for collagen binding. Evidence was obtained
      that divalent cations are not required for collagen binding to the I domain
      fragment, indicating that divalent cations are not involved in the actual binding
      to collagen but probably in the regulation of the binding. We identified Thr-221
      within the previously identified putative ligand binding region as a residue
      critical for collagen binding to both alpha 2 beta 1 and the I domain fragment.
      Thr-221 may be involved in the actual collagen binding and recognition.

PMID- 7523398
TI  - Inhibition of transcription in vitro by binding of DNA (cytosine-5)-methylases to
      DNA templates containing cytosine analogs.
AB  - DNA(cytosine-5)-methylases form tight complexes at their methylation sites when
      the target cytosine residue is substituted by analogs such as 5-azacytosine or 5
      fluorocytosine. To test whether such complexes can block RNA transcription in
      vitro, template DNA-containing methylation sites were prepared, in which cytosine
      residues in either the (+)- or (-)-strand were substituted by the analogs. Such
      templates, irrespective of the strand in which substitution was made, could
      effectively block the elongation of RNA at specific sites when complexed with
      EcoRII methylase. The protein-DNA complex probably prevents the unwinding of the
      template strands or might directly present itself as a steric block to the
      advancing RNA polymerase. RNA synthesis was also inhibited at specific sites due
      to complex formation between azacytosine-containing DNA and two other methylases,
      HhaI and HpaII. The 3' ends of the interrupted transcripts were mapped and were
      found to lie within 13-14, 13, and 23 nucleotides of the binding sites on the (-)
      strand for HhaI, HpaII, and EcoRII methylases, respectively. Exonuclease III
      footprinting revealed that the boundaries of the complexed methylases, HhaI,
      HpaII, and EcoRII, on the (-)-strand were within 2-3, 1-2, and 9-10 nucleotides,
      respectively, of the last nucleotide copied by the RNA polymerase.

PMID- 7523400
TI  - Transport of polypeptide ionophores into proteoliposomes reconstituted with rat
      liver P-glycoprotein.
AB  - The aim of this study was to examine the peptide transport activity of a
      naturally occurring P-glycoprotein such as that present in rat liver canalicular
      membrane vesicles. The peptide ionophores valinomycin and gramicidin D, which are
      known substrates of P-glycoprotein, served to monitor the P-glycoprotein activity
      indirectly as the ATP-dependent uptake of 86Rb+ mediated by these ionophores.
      Canalicular membrane vesicles proved inherently permeable to K+ ions, which
      prevented assay of transport ionophore activity. Therefore, P-glycoprotein was
      extracted from canalicular membrane vesicles and reconstituted into
      proteoliposomes that are relatively impermeable to cations. P-glycoprotein
      activity in the proteoliposomes was dependent on ATP hydrolysis since it was not
      observed with non-hydrolyzable analogs of ATP. Maximal ATP-dependent 86Rb+ uptake
      occurred at 50 nM gramicidin D and at 500 nM valinomycin thus possibly reflecting
      higher affinity of P-glycoprotein for gramicidin D. Nigericin, which does not
      participate in the multidrug resistance phenomenon, did not support an ATP
      dependent uptake of 86Rb+. ATP hydrolysis increased the amount of 86RB+
      transported into the proteoliposomes. Furthermore, preincubation of the
      proteoliposomes in the presence of gramicidin D and 86Rb+, allowing for maximal
      ATP-independent 86Rb+ uptake to occur, did not interfere with subsequent ATP
      dependent uptake, indicating the latter to constitute an active transport
      mechanism. The ATP-dependent component of 86Rb+ uptake occurred neither with
      liposomes nor with proteoliposomes reconstituted with proteins extracted from
      sinusoidal vesicles that lack P-glycoprotein. The ATP-dependent uptake was
      blocked by the known inhibitors of the ATPase activity associated with P
      glycoprotein, oligomycin and vanadate, as well as by its established substrates,
      daunorubicin, doxorubicin, vinblastine, and the tripeptide N-acetyl-leucyl-leucyl
      norleucinal. Thus, the reconstituted P-glycoprotein catalyzes the ATP-dependent
      86Rb+ uptake that appears to occur by an energy-dependent translocation of the
      86Rb(+)-ionophore complex. In this case, the actual substrate of P-glycoprotein
      is the ionophore-cation complex, which is both hydrophobic and positively charged
      as are most of the substrates of P-glycoprotein. This is the first demonstration
      of transport of a naturally occurring polypeptide by proteoliposomes
      reconstituted with physiologically expressed P-glycoprotein.

PMID- 7523402
TI  - Complete primary structure of the human type IV collagen alpha 4(IV) chain.
      Comparison with structure and expression of the other alpha (IV) chains.
AB  - The entire sequence of the human alpha 4(IV) collagen chain was determined from
      cDNA clones and polymerase chain reaction-amplified DNAs. The complete
      translation product has 1,690 amino acid residues and the processed alpha 4(IV)
      chain proper 1,652 residues. There is a 38-residue putative signal peptide, a
      1,421-residue collagenous domain starting with a 23-residue noncollagenous
      sequence, and a 231-residue NC1 domain. The Gly-Xaa-Yaa-repeat sequence of the
      collagenous domain is interrupted at 26 locations by noncollagenous sequences of
      1-12 residues in length. The alpha 4(IV) chain contains 31 cysteine residues of
      which 18 are conserved in the other type IV collagen alpha chains. The calculated
      molecular weight of the mature alpha 4(IV) chain is 164,123. Analysis of the
      primary structure showed that the alpha 4(IV) chain belongs to the alpha 2-like
      type IV collagen chains together with alpha 2(IV) and alpha 6(IV). Northern
      analyses with RNA from several human fetal tissues revealed quite similar
      expression patterns for the alpha 4(IV) and alpha 3(IV) chains, but there were
      also distinct differences in some tissues. The expression patterns of alpha 5(IV)
      and alpha 6(IV) differed extensively between each other and they also differed
      from those of alpha 3(IV) and alpha 4(IV).

PMID- 7523405
TI  - The effect of N-linked glycosylation on activity of the Na(+)- and Cl(-)
      dependent serotonin transporter expressed using recombinant baculovirus in insect
      cells.
AB  - The rat Na(+)- and Cl(-)-dependent serotonin transporter was expressed in Sf9
      insect cells using the baculovirus system. Expression of the serotonin
      transporter caused the Sf9 cells to accumulate [3H]serotonin (Km 78 nM) and to
      bind the specific transport inhibitor [125I]RT155 (2 beta-carbomethoxy-3 beta-(4
      [125I]iodophenyl)tropane) (Kd 0.22 nM). Ligand binding assays on isolated
      membranes showed 500,000 copies of the serotonin transporter/cell (9 pmol/mg of
      membrane protein). Immunoreactive bands of apparent M(r) 54,000 (unglycosylated)
      and 60,000 (glycosylated) were observed in Western blots of membrane proteins
      from infected cells. The 54-kDa band was significantly smaller than the expected
      M(r) of 72,500 predicted from the cDNA sequence. The 54-kDa band was shown to
      represent the intact serotonin transporter by expressing a recombinant serotonin
      transporter that contained c-Myc and FLAG epitope tags engineered at the N and C
      termini, respectively. Both tags were present on a membrane protein that migrated
      slightly slower than the previously observed 54-kDa band, consistent with the
      extra mass added by the tags. The tags did not affect the Kd for [125I]RT155
      binding. The effect of N-linked glycosylation on ligand binding and the level of
      expression were studied. The expression of the serotonin transporter in
      tunicamycin-treated Sf9 cells resulted in low levels of ligand binding activity
      (0.2 pmol/mg) but unchanged Kd. Similarly, mutated serotonin transporters that
      contained reduced numbers of N-linked glycosylation sites had unchanged Kd for
      [125I]RT155 binding whether there were 2, 1, or 0 N-linked glycosylation sites
      present on the serotonin transporter. In contrast, Bmax was dramatically reduced;
      levels of expression of the unglycosylated serotonin transporter (0.4 pmol/mg)
      were 20-fold lower compared with levels of the fully glycosylated serotonin
      transporter. The Km for [3H]serotonin uptake was also unchanged. These data
      indicate that glycosylation is required for optimal stability of the serotonin
      transporter in the membrane but not for serotonin transport or ligand binding per
      se.

PMID- 7523406
TI  - Identity of a peptide domain of human C9 that is bound by the cell-surface
      complement inhibitor, CD59.
AB  - The CD59 antigen is a plasma membrane glycoprotein that serves as an inhibitor of
      the C5b-9 complex of complement. This inhibitory activity appears related to the
      capacity of CD59 to bind with high affinity to sites that are nascently exposed
      in the alpha-chain subunit of human C8, as well as within the C9b domain (amino
      acid residues 245-538) of human C9, during assembly of the C5b-9 complex on the
      target membrane (Ninomiya, H., and Sims, P. J. (1992) J. Biol. Chem. 267, 13675
      13680). The CD59 binding site in C9 was first investigated by N-terminal
      sequencing of CD59-binding peptides generated by limited digest of the isolated
      C9b domain. These experiments revealed a 17-kDa fragment (starting at C9 residue
      Thr-320) that retained affinity for CD59, suggesting the possibility for
      localizing the CD59 binding site by mapping with small C9-derived peptides.
      Peptides spanning the entire C9b sequence were expressed in Escherichia coli and
      then probed with CD59. CD59 bound specifically to all peptides starting N
      terminal to C9 residue 359 with C termini extending beyond residue 411. Little to
      no CD59 binding was observed for various C9-derived peptides that started C
      terminal to residue 359 or that were truncated N-terminal to residue 411.
      Affinity-purified antibody against C9 residues 320-411 inhibited CD59 binding to
      C9 by > 50% and completely inhibited its binding to the isolated C9b domain.
      Little to no specific binding of CD59 was detected for peptides restricted to the
      putative hinge domain within C9b (residues 245-271). These results indicate that
      a CD59 binding site is located between residues 320 and 411 of the C9 polypeptide
      and suggest that the affinity of this site is principally determined by residues
      359-411.

PMID- 7523404
TI  - Type I procollagen COOH-terminal proteinase enhancer protein: identification,
      primary structure, and chromosomal localization of the cognate human gene
      (PCOLCE).
AB  - Type I procollagen COOH-terminal proteinase (C-proteinase) enhancer, a
      glycoprotein that binds to the COOH-terminal propeptide of type I procollagen and
      enhances procollagen C-proteinase activity, was purified from mouse fibroblast
      culture media. Partial amino acid sequences obtained from proteolytic fragments
      were found to have identity with the deduced amino acid sequence of a cDNA clone
      of unknown function, previously isolated from a mouse astrocyte library.
      Sequences of mouse enhancer cDNA, obtained in the present study, predict a
      approximately 50-kDa, 468-amino acid protein that differs from the 43-kDa, 402
      amino acid protein predicted by the previously reported astrocyte-derived clone.
      Human cDNAs encode an enhancer of 449 amino acids. Previous biochemical studies
      have found the mouse enhancer as a 55-kDa form, which is readily processed to 36-
      and 34-kDa forms, retaining full C-proteinase enhancing activity and the ability
      to bind the COOH-terminal propeptide. Data presented here show the 36-kDa form to
      correspond to the amino-terminal portion of the 55-kDa protein. This is the most
      conserved region between mouse and human enhancers, comprising two domains with
      homology to domains found in a number of proteases and proteins with
      developmental functions. Such domains are thought to mediate interactions between
      proteins. Mouse enhancer RNA is shown to be at highest levels in collagen-rich
      tissues, especially tendon. The human enhancer gene, PCOLCE, is localized to
      7q21.3-->q22, the same chromosomal region containing the type I collagen alpha 2
      chain gene, COL1A2.

PMID- 7523403
TI  - Interleukin-6 signaling via four transcription factors binding palindromic
      enhancers of different genes.
AB  - Interferons (IFNs), as well as some interleukins, growth factors, and hormones,
      all induce tyrosine phosphorylation of STAT1 and additional transcription factors
      of similar sizes. These factors are activated to translocate to nucleus and bind
      to enhancers of consensus sequence TTnCnnnAA (gamma-IFN activated sequence-like
      enhancers). In mammary cells or hybridoma B9 cells, four distinct tyrosine
      phosphorylated transcription complexes activated by interleukin-6 (IL-6) and IFN
      beta were observed: pIRFA and complexes I, II, and III (of increasing
      electrophoretic mobility). The factors have unequal affinities for enhancers of
      different genes; they are activated with distinct kinetics and to different
      extents by IL-6 and IFNs. The pIRFA band isolated from IL-6-stimulated B9
      hybridoma cells revealed three DNA-interacting components: two large subunits of
      91 and 98 kDa, as well as a small component of 46 kDa not seen in other complexes
      analyzed. One of the large pIRFA subunits may be APRF/STAT3, since pIRFA reacted
      with anti-APRF antibodies as do complexes I and II. However, pIRFA did not react
      with antibodies to STAT1, indicating STAT1 is not the other large component of
      pIRFA. Complex II, which reacted to anti-acute phase response factor antibodies
      also reacted to anti-STAT1 antibodies, whereas complex III reacted only to anti
      STAT1 and was the only complex resistant to N-ethylmaleimide. By its multimeric
      subunit structure and its cytokine and enhancer sequence specificities, the
      slowly migrating pIRFA band appears as a novel tyrosine-phosphorylated
      transcription complex acting on a subset of gamma-IFN activated sequence-like
      enhancers.

PMID- 7523401
TI  - L-thiocitrulline. A stereospecific, heme-binding inhibitor of nitric-oxide
      synthases.
AB  - Nitric-oxide synthase (NOS) catalyzes the oxidation of L-arginine to citrulline
      and nitric oxide (NO). The enzyme is inhibited by a variety of N omega
      monosubstituted L-arginine analogs, and some of these compounds are useful in
      reversing pathologies associated with the overproduction of NO (e.g. the
      hypotension of septic shock). We report here that L-thiocitrulline (gamma
      thioureido-L-norvaline) is a potent, stereospecific inhibitor of the constitutive
      brain and endothelial isoforms of NOS as well as the isoform induced in vascular
      smooth muscle cells by lipopolysaccharide and interferon-gamma. Steady state
      kinetic studies show L-thiocitrulline inhibition is competitive with L-arginine
      (Ki approximately 4-20% of KArgm), indicating that initial binding is as a
      substrate/product analog. In contrast to L-arginine and N omega-methyl-L
      arginine, the prototypic NOS inhibitor, L-thiocitrulline binding elicits a "Type
      II" difference spectrum, indicating a high spin to low spin transition of the
      iron in the heme cofactor. This finding suggests that L-thiocitrulline is
      contributing the sixth ligand to heme iron, probably through the thioureido
      sulfur. Such interaction with heme iron neither stimulates nor inhibits the
      direct flavin-mediated cytochrome c reduction activity of the enzyme, but it does
      inhibit heme-dependent superoxide formation. In vivo, L-thiocitrulline is a
      potent pressor agent in both normal and endotoxemic rats, the latter finding
      suggesting utility in treating the hypotension of septic shock.

PMID- 7523407
TI  - Molecular analysis of the interaction of calcineurin with drug-immunophilin
      complexes.
AB  - The calcium/calmodulin-regulated phosphatase calcineurin (CN) is the site of
      action of the immunosuppressive drugs cyclosporin A (CsA) and FK506. CN has
      recently been established as a key signaling enzyme in the T cell signal
      transduction cascade and an important regulator of transcription factors such as
      NF-AT and OAP/Oct-1, which are involved in the expression of a number of
      important T cell early genes. CsA and FK506 act by forming complexes with their
      respective intracellular receptors cyclophilin and FKBP (immunophilins), which
      can then bind to CN, inhibiting its enzymatic activity and thereby preventing
      early gene expression. CN is comprised of two subunits: a 59-kDa catalytic
      subunit (CNA), which contains a calmodulin binding domain and autoinhibitory
      region, and a 19-kDa intrinsic calcium binding regulatory subunit (CNB). In this
      study, we have utilized a series of deletion mutants of the CNA subunit to
      investigate the subunit and molecular requirements that govern the interaction of
      CN with drug-immunophilin complexes. The calmodulin binding and autoinhibitory
      domains of the CNA subunit were found to be dispensable for the binding of CN to
      drug-immunophilin complexes. In contrast, we found that the regulatory CNB
      subunit appears to play an obligatory role in this interaction and have defined
      an amino acid sequence of the CNA subunit which forms the binding site for CNB.
      Although necessary, the CNB subunit per se is not sufficient to mediate an
      interaction with drug-immunophilin complexes; amino acid residues of the CNA
      subunit, specifically a region located within the putative catalytic domain, are
      also required for the interaction of CN with both FKBP-FK506 and cyclophilin A
      CsA.

PMID- 7523409
TI  - Potent and selective inhibition of human nitric oxide synthases. Inhibition by
      non-amino acid isothioureas.
AB  - S-Ethylisothiourea was a potent competitive inhibitor of human nitric oxide
      synthase (NOS), with Ki values of 17, 36, and 29 nM for the inducible (i),
      endothelial (e), and neuronal (n) isozymes, respectively. Unlike some potent
      inhibitors of NOS, no time dependence was observed. S-Ethylisothiourea was not a
      detectable substrate for eNOS. S-Ethylisothiourea was also a potent inhibitor of
      mouse iNOS (Ki value of 5.2 nM), and its binding perturbed the spectrum of iNOS
      consistent with its altering the environment of the bound heme. The optimum
      binding of S-ethyl- and S-isopropylisothiourea relative to 70 other analogs
      suggested that these alkyl substitutions fit into a small hydrophobic pocket.
      Most isothioureas were 2-6-fold selective for the human iNOS (Ki for iNOS versus
      Ki for eNOS), with one being 19-fold selective. The cyclized mimics of S
      ethylisothiourea, 2-NH2-thiazoline, and 2-NH2-thiazole, were also competitive
      inhibitors of human NOS. A third structural class of inhibitors, bisisothioureas,
      were, in general, the most selective in their inhibition of human iNOS. S,S'-(1,3
      Phenylenebis(1,2-ethanediyl))bisisothiourea was 190-fold selective (Ki value of
      0.047 microM against iNOS versus 9.0 microM against eNOS). These results
      demonstrate that potent and selective inhibition of human NOS isozymes is
      achievable.

PMID- 7523408
TI  - Mutating the "primer grip" of p66 HIV-1 reverse transcriptase implicates
      tryptophan-229 in template-primer utilization.
AB  - "BcgI cassette" mutagenesis was used to prepare variants of p66 human
      immunodeficiency virus (HIV)-1 reverse transcriptase with amino acid
      substitutions between residues Glu224 and Trp229. Mutant polypeptides were
      reconstituted in vitro with wild type p51 to generate the "selectively mutated"
      heterodimer series p66(224A)/p51-p66(229A)/p51. Purified enzymes were
      characterized with respect to dimerization, DNA polymerase, RNase H, and tRNA(Lys
      3) binding. The combined analyses indicate that while alteration of p66 residues
      Glu224-Leu228 has minimal consequences, the DNA polymerase activities of mutant
      p66(229A)/p51 are impaired. DNase I footprinting illustrates that this mutant
      does not form a stable replication complex with a model template-primer. In vivo
      studies indicate that the equivalent mutation eliminates viral infectivity,
      suggesting a contribution of Trp229 toward architecture of the p66 primer grip.

PMID- 7523410
TI  - Potent and selective inhibition of human nitric oxide synthases. Selective
      inhibition of neuronal nitric oxide synthase by S-methyl-L-thiocitrulline and S
      ethyl-L-thiocitrulline.
AB  - Potent and selective inhibition of neuronal nitric oxide synthase (nNOS) compared
      to endothelial NOS (eNOS) and inducible NOS (iNOS) may be useful to treat
      cerebral ischemia (stroke) and other neurodegenerative diseases. S-Methyl-L
      thiocitrulline (Me-TC) and S-ethyl-L-thiocitrulline (Et-TC) inhibited the
      oxidation of L-arginine and the L-arginine-independent oxidation of NADPH by nNOS
      from human brain. Me-TC and Et-TC were slow, tight binding inhibitors of nNOS
      with second-order association rate constants (kon) of 2.6 x 10(5) M-1 s-1 and 1.3
      x 10(5) M-1 s-1, respectively. The respective dissociation rate constants (koff)
      were 3 x 10(-4) s-1 and 0.7 x 10(-4) s-1. Thus, the Kd values calculated from
      koff/kon were 1.2 and 0.5 nM, respectively. L-Arginine was a competitive
      inhibitor of Me-TC and Et-TC binding with competition constant (Ks) values of 2.2
      and 2.7 microM, respectively. The Km of nNOS for L-arginine was 1.6 microM. The
      active site concentration of nNOS was estimated by titration with Et-TC. Based on
      this active site concentration, a kcat of 0.4 s-1 for the oxidation of L
      arginine, was calculated. Me-TC and Et-TC were less potent inhibitors of human
      iNOS (Ki values of 34 and 17 nM, respectively) and human eNOS (Ki values of 11
      and 24 nM). Thus, Me-TC and Et-TC were 10- and 50-fold, respectively, more potent
      inhibitors of nNOS than eNOS. Furthermore, Me-TC was also 17-fold selective for
      rat nNOS in neuronal tissue compared to rat eNOS in vascular endothelium,
      suggesting that Me-TC may be selective for nNOS in vivo and therefore, may be
      therapeutically useful to treat neurodegenerative diseases.

PMID- 7523412
TI  - Structure-function analysis of angiotensin I-converting enzyme using monoclonal
      antibodies. Selective inhibition of the amino-terminal active site.
AB  - Angiotensin I-converting enzyme (ACE; kininase II) contains two very similar
      domains (the NH2- and COOH-terminal domains (N and C domains, respectively)),
      each bearing an active site. These active sites hydrolyze the same peptides, but
      do not have the same catalytic properties and substrate specificities. In an
      attempt to develop domain-specific immunological probes, two series of monoclonal
      antibodies (mAbs), 19 clones in all, were produced and tested against human ACE.
      These mAbs recognized at least nine different epitopes within three antigenic
      regions of the ACE molecule. Testing on wild-type recombinant ACE and several
      mutants with only one intact domain showed that these epitopes were all located
      in the N domain. None of the mAbs recognized the C domain. This particular
      specificity and analysis of results obtained with several polyclonal antibodies
      to human ACE suggest that ACE immunogenicity is determined mainly by the N
      domain. Two mAbs (3A5 and i2H5) recognizing epitopes from different antigenic
      regions of ACE inhibited the enzymatic activity of the N (but not of the C)
      domain. mAb 3A5 had the same inhibitory potency toward hippuryl-His-Leu,
      benzyloxycarbonyl-Phe-His-Leu, and angiotensin I hydrolysis, with 50% inhibition
      achieved at a mAb/ACE molar ratio of 6. mAb i2H5 was roughly three times more
      effective than mAb 3A5 inhibiting the hydrolysis of benzyloxycarbonyl-Phe-His-Leu
      and the natural substrates angiotensin I and bradykinin (50% inhibition at a
      molar ratio of 1-2), but was less effective in inhibiting hippuryl-His-Leu
      cleavage (50% inhibition at a molar ratio of 22-25), indicating that this
      substrate interacts with a specific subsite. mAb i2H5 almost completely inhibited
      the hydrolysis of the luteinizing hormone-releasing hormone by the isolated N
      domain. Both the primary carboxyl- and amino-terminal cleavages of this peptide
      were suppressed. This antibody suppressed the primary amino-terminal cleavage of
      the luteinizing hormone-releasing hormone by wild-type ACE by > 90%, indicating
      that this particular ACE function is mediated mainly by the N domain active site.
      These data provide evidence for structural differences between the two homologous
      domains of ACE despite their high degree of sequence homology and show that
      monoclonal antibodies are able to distinguish between the two active sites in
      ACE.

PMID- 7523411
TI  - The integrin alpha 9 beta 1 mediates cell attachment to a non-RGD site in the
      third fibronectin type III repeat of tenascin.
AB  - We have previously reported the sequence of the integrin alpha 9 subunit, a
      partner of the beta 1 subunit that is expressed in basal keratinocytes,
      hepatocytes, airway epithelial cells, and smooth and skeletal muscle. In the
      present study, we have stably expressed alpha 9 beta 1 on the surface of the
      human embryonic kidney cell line 293 and the human colon carcinoma cell line
      SW480 and used these transfected cells lines to identify ligand(s) for this
      integrin. Transfected cells did not appear to utilize alpha 9 beta 1 for
      attachment to the extracellular matrix proteins fibronectin, laminin,
      vitronectin, fibrinogen, thrombospondin, or type I or IV collagen. However, in
      contrast to mock transfectants, both 293 cells and SW480 cells expressing alpha 9
      beta 1 adhered to intact chicken tenascin. By utilizing a variety of recombinant
      fragments of tenascin, we were able to localize the binding site for alpha 9 beta
      1 to the third type III repeat. This repeat contains the arginine-glycine
      aspartic acid (RGD) tripeptide that has been shown to serve as a binding site in
      tenascin for alpha v-integrins. However, the RGD site does not appear to be the
      binding site for alpha 9 beta 1, as the attachment of alpha 9 transfectants to
      this fragment was not inhibited by RGD peptide, nor by changing the RGD site to
      RAD or RAA.

PMID- 7523414
TI  - Vitronectin-driven human keratinocyte locomotion is mediated by the alpha v beta
      5 integrin receptor.
AB  - Vitronectin is a soluble serum factor that is known to promote epiboly of
      keratinocytes in explant cultures and enhance cell spreading and attachment to
      matrix. Recently, vitronectin was demonstrated to promote human keratinocyte
      locomotion. The mechanism(s) by which vitronectin enhances keratinocyte migration
      is unknown. In this study, we quantitated the vitronectin-driven migration of
      human keratinocytes in the presence of antibodies to vitronectin receptors. We
      found that vitronectin's effect of promoting human keratinocyte migration was
      inhibited by antibody-directed against the alpha v beta 5 receptor. In addition,
      we surface-labeled human keratinocytes, chromatographed extracts of the cell
      membranes on a vitronectin column, and then immunoprecipitated the bound and
      eluted proteins with antibodies to specific vitronectin receptors. We identified
      the vitronectin receptors on human keratinocytes as bands of 150,000 and 100,000
      daltons without reduction and as 125,000 and 110,000 daltons under reducing
      conditions. Immunoprecipitation with specific antibodies identified the major
      receptor to be the alpha v beta 5 integrin. In addition, we quantitated
      vitronectin-driven migration of human keratinocytes in the presence of Arg-Gly
      Asp (RGD) and control peptides. We found that the presence of RGD, but not
      control peptide, inhibited vitronectin-driven migration of human keratinocytes.
      These studies demonstrate that human keratinocytes express vitronectin receptors
      and use the alpha v beta 5 receptor for cellular locomotion.

PMID- 7523415
TI  - The pro region of human intestinal lactase-phlorizin hydrolase.
AB  - Human small intestinal lactase-phlorizin hydrolase (LPH) is synthesized as a
      single-chain polypeptide precursor, prepro-LPH, that undergoes two sequential
      cleavage steps: the first in the endoplasmic reticulum to pro-LPH (215-kDa) and
      the second, following terminal glycosylation in the Golgi apparatus, to mature
      160-kDa LPH (denoted LPH beta). The LPH beta molecule is subsequently targetted
      to the brush-border membrane. Characterization of the N-terminal profragment
      (denoted LPH alpha) of pro-LPH using an epitope-specific, anti-peptide polyclonal
      antibody reveals that LPH alpha (i) has an apparent molecular weight of
      approximately 100,000, (ii) is not associated with LPH beta after cleavage of pro
      LPH has occurred, and (iii) is not transported to the cell surface or secreted
      into the extracellular medium. In biosynthetic labeling experiments, a clear
      precursor/product relationship could be demonstrated between pro-LPH and the LPH
      alpha and LPH beta polypeptides. Further, LPH alpha has a significantly shorter
      half-life than LPH beta. LPH alpha is neither N- nor O-glycosylated, despite the
      presence of 5 potential N-glycosylation sites. LPH alpha, which is rich in
      cysteine and hydrophobic amino acid residues, may fold rapidly into a tight and
      rigid globular domain in which carbohydrate attachment sites are no longer
      accessible to glycosyltransferases. When expressed independently in COS-1 cells,
      the LPH beta polypeptide forms a misfolded, transport-incompetent molecule. We
      propose a role for the LPH alpha domain within the pro-LPH molecule as an
      intramolecular chaperone during folding in the ER.

PMID- 7523416
TI  - Adhesion receptor activation of phosphatidylinositol 3-kinase. von Willebrand
      factor stimulates the cytoskeletal association and activation of
      phosphatidylinositol 3-kinase and pp60c-src in human platelets.
AB  - The cytoskeleton participates in the coordinated regulation of intracellular
      signaling molecules, following agonist stimulation of cells. We have demonstrated
      that von Willebrand factor (vWF) induced the cytoskeletal association and
      activation of phosphatidylinositol 3-kinase (PtdIns 3-kinase) in human platelets.
      The activation of PtdIns 3-kinase coincided with the tyrosine phosphorylation of
      multiple platelet proteins, as assessed by anti-phosphotyrosine immunoblotting.
      One of these tyrosine-phosphorylated proteins, pp60c-src, became specifically
      enriched in the cytoskeletal fraction of vWF-stimulated platelets. The vWF
      stimulated cytoskeletal association of PtdIns 3-kinase and pp60c-src required
      platelet stirring and aggregation, was specifically blocked by an anti-GPIb
      monoclonal antibody, and was not observed in platelets lacking the glycoprotein
      Ib/IX complex (Bernard-Soulier syndrome). Pretreatment of normal platelets with 5
      mM EDTA (37 degrees C for 90 min) or RGDS (2 mM), which disrupts the binding of
      various adhesive proteins to platelet integrins and inhibits fibrinogen-mediated
      platelet aggregation, did not alter the vWF-stimulated activation and
      cytoskeletal association of PtdIns 3-kinase and pp60c-src. Pretreatment of
      platelets with acetylsalicylic acid (1 mM) completely abolished vWF-stimulated
      production of thromboxane A2, dense granule release, and the activation of
      protein kinase C, without altering the activation and cytoskeletal translocation
      of PtdIns 3-kinase and pp60c-src. Our results suggest that vWF binding to the
      platelet adhesion receptor glycoprotein Ib/IX can mediate activation and
      translocation of both tyrosine and lipid kinase(s) independent of other agonists.

PMID- 7523413
TI  - Export of protein from the endoplasmic reticulum is regulated by a
      diacylglycerol/phorbol ester binding protein.
AB  - The export of vesicular stomatitis virus glycoprotein (VSV-G) from the
      endoplasmic reticulum (ER) involves sorting and concentration, and has been
      proposed to require the function of heterotrimeric G proteins. To begin to
      identify the basic elements of a potential signaling pathway involved in vesicle
      assembly, we have examined whether protein kinase C (PKC) is required for ER to
      Golgi transport. Calphostin C, a specific inhibitor of the highly conserved
      cysteine-rich C6H2 motif present in the regulatory domain of PKC was found to be
      a potent inhibitor of export of VSV-G and vesicle budding from the ER in vivo and
      in vitro (IC50 approximately 60 nM). In contrast, the diacylglycerol analog
      phorbol 12-myristate 13-acetate, which activates PKC, enhanced the migration of
      VSV-G from the ER to pre-Golgi intermediates. Neither reagent had detectable
      effects on the oligomerization of VSV-G prior to export nor perturbed transport
      of protein between compartments of the Golgi stack. In contrast to the striking
      effects of calphostin C, reagents that inhibit the function of the catalytic
      domain of PKC (including the general kinase inhibitor staurosporine, as well as
      the more specific inhibitors H-7, H-8, pseudosubstrate inhibitor, or
      chelerythrine) did not inhibit export from the ER. Export was also insensitive to
      down-regulation of various PKC isoforms. These results suggest that a novel
      protein containing the conserved C6H2 motif may serve as a potential link in a
      signaling pathway regulating vesicle budding from the ER.

PMID- 7523417
TI  - Dopamine-induced inhibition of endogenous acetylcholine release from the isolated
      ileal synaptosomal preparations of guinea-pig mediated via alpha-adrenoceptors.
AB  - 1. The effect of exogenous dopamine on the release of endogenous acetylcholine
      (ACh) from isolated ileal synaptosomal guinea-pig preparations was examined by
      means of high pressure liquid chromatography with electrochemical detection. 2.
      Release of ACh was induced by substance P or by depolarization with high
      potassium (50 mM) in a medium containing atropine propranolol and naloxone. 3.
      Dopamine produced a concentration-dependent inhibition of the evoked ACh release
      induced by substance P or in samples depolarized by high potassium. This action
      of dopamine was not reversed by the dopamine receptor antagonists either for the
      DA2 subtype domperidone, or for the DA1 subtype, SCH23390. Fenoldopam, the
      agonist of dopamine DA1 receptors, or quinpirole, the agonist of dopamine DA2
      receptors, reduced the evoked ACh release, although only in high, non-dopamine
      specific concentrations. 4. Failure of guanethidine or desipramine to inhibit
      this effect of dopamine ruled out mediation by endogenous noradrenaline. 5.
      Idazoxan and yohimbine reversed this dopamine-induced inhibition at concentration
      sufficient to abolish the action of clonidine. Influx of (45)Ca stimulated by
      substance P or high potassium into synaptosomal preparations was attenuated in
      the presence of dopamine. This inhibition by dopamine was also reversed by
      idazoxan or yohimbine but not by dopamine receptor antagonists. Moreover, the
      dopamine-induced inhibitions of both the ACh release and the influx of (45)Ca
      disappeared in the samples treated with pertussis toxin at a dose sufficient to
      abolish the action of clonidine. 6. It is concluded that dopamine suppresses the
      influx of calcium ions into cholinergic nerve terminals via an activation of
      alpha2-adrenoceptors coupled with a pertussis toxin-sensitive GTP-binding
      protein, resulting in the decrease of ACh release from ileal synaptosomes of
      guinea-pigs.

PMID- 7523419
TI  - Identification of the major physiologic phosphorylation site of human keratin 18:
      potential kinases and a role in filament reorganization.
AB  - There is ample in vitro evidence that phosphorylation of intermediate filaments,
      including keratins, plays an important role in filament reorganization. In order
      to gain a better understanding of the function of intermediate filament
      phosphorylation, we sought to identify the major phosphorylation site of human
      keratin polypeptide 18 (K18) and study its role in filament assembly or
      reorganization. We generated a series of K18 ser-->ala mutations at potential
      phosphorylation sites, followed by expression in insect cells and comparison of
      the tryptic 32PO4-labeled patterns of the generated constructs. Using this
      approach, coupled with Edman degradation of the 32PO4-labeled tryptic peptides,
      and comparison with tryptic peptides analyzed after labeling normal human colonic
      tissues, we identified ser-52 as the major K18 physiologic phosphorylation site.
      Ser-52 in K18 is not glycosylated and matches consensus sequences for
      phosphorylation by CAM kinase, S6 kinase and protein kinase C, and all these
      kinases can phosphorylate K18 in vitro predominantly at that site. Expression of
      K18 ser-52-->ala mutant in mammalian cells showed minimal phosphorylation but no
      distinguishable difference in filament assembly when compared with wild-type K18.
      In contrast, the ser-52 mutation played a clear but nonexclusive role in filament
      reorganization, based on analysis of filament alterations in cells treated with
      okadaic acid or arrested at the G2/M stage of the cell cycle. Our results show
      that ser-52 is the major physiologic phosphorylation site of human K18 in
      interphase cells, and that its phosphorylation may play an in vivo role in
      filament reorganization.

PMID- 7523418
TI  - Cell nucleus and DNA fragmentation are not required for apoptosis.
AB  - Apoptosis is the predominant form of cell death and occurs under a variety of
      physiological and pathological conditions. Cells undergoing apoptotic cell death
      reveal a characteristic sequence of cytological alterations including membrane
      blebbing and nuclear and cytoplasmic condensation. Activation of an endonuclease
      which cleaves genomic DNA into internucleosomal DNA fragments is considered to be
      the hallmark of apoptosis. However, no clear evidence exists that DNA degradation
      plays a primary and causative role in apoptotic cell death. Here we show that
      cells enucleated with cytochalasin B still undergo apoptosis induced either by
      treatment with menadione, an oxidant quinone compound, or by triggering APO
      1/Fas, a cell surface molecule involved in physiological cell death. Incubation
      of enucleated cells with the agonistic monoclonal anti-APO-1 antibody revealed
      the key morphological features of apoptosis. Moreover, in non-enucleated cells
      inhibitors of endonuclease blocked DNA fragmentation, but not cell death induced
      by anti-APO-1. These data suggest that DNA degradation and nuclear signaling are
      not required for induction of apoptotic cell death.

PMID- 7523420
TI  - Integrin alpha v beta 5 selectively promotes adenovirus mediated cell membrane
      permeabilization.
AB  - Human adenovirus type 2 (Ad2) enters host cells by receptor-mediated endocytosis,
      an event mediated by the virus penton base binding to cell surface integrins
      alpha v beta 3 and alpha v beta 5. While both alpha v integrins promote virus
      internalization, alpha v beta 5 is involved in the subsequent event of membrane
      permeabilization. Cells transfected with the beta 5 or beta 3 subunit, expressing
      either alpha v beta 5 and alpha v beta 3, respectively, were capable of
      supporting Ad2 infection to varying degrees. In this case, cells expressing alpha
      v beta 5 were significantly more susceptible to Ad2-induced membrane
      permeabilization, as well as to Ad2 infection, than cells expressing alpha v beta
      3. Adenovirus-mediated gene delivery was also more efficient in cells expressing
      alpha v beta 5. These results suggest that the interaction of alpha v beta 5 with
      Ad2 penton base facilitates the subsequent step of virus penetration into the
      cell. These studies provide evidence for the involvement of a cellular receptor
      in virus-mediated membrane permeabilization and suggest a novel biological role
      for integrin alpha v beta 5 in the infectious pathway of a human adenovirus.

PMID- 7523422
TI  - Inhibition of anchorage-dependent cell spreading triggers apoptosis in cultured
      human endothelial cells.
AB  - When cultivated on substrates that prevent cell adhesion (the polymer
      polyhydroxyethylmethacrylate, bovine serum albumin, and Teflon), human
      endothelial cells (EC) rapidly lost viability with a half-life of approximately
      10 h. Dying EC showed the morphological and biochemical characteristics of
      apoptosis. The apoptotic process of suspended EC was delayed by the protein
      synthesis inhibitor cycloheximide. To obtain information as to the mechanism
      involved in the apoptosis of suspended EC, we investigated whether adhesion to
      matrix proteins or integrin occupancy in EC retaining a round shape may affect EC
      suicide. EC bound to low coating concentration of either fibronectin or
      vitronectin, retaining a round shape and failing to organize actin
      microfilaments, underwent to rapid cell death; by contrast, cells on high
      substrate concentrations became flattened, showed actin microfilament
      organization, and retained viability. Addition of saturating amounts of soluble
      vitronectin to suspended round-shaped EC did not reduce the process of apoptosis.
      Finally, when suspended EC bound Gly-Arg-Gly-Asp-Ser-coated microbeads
      (approximately 10 microbeads/cell), yet retaining a round shape, the apoptotic
      process was not affected. Oncogene-transformed EC in suspension were less
      susceptible to cell death and apoptosis than normal EC. Overall, these data
      indicate that cell attachment to matrix or integrin binding per se is not
      sufficient for maintaining cell viability, and that cells need to undergo some
      minimal degree of shape change to survive. Modulation of interaction with the
      extracellular matrix can, therefore, be an important target for the control of
      angiogenesis.

PMID- 7523421
TI  - Increased expression of keratin 16 causes anomalies in cytoarchitecture and
      keratinization in transgenic mouse skin.
AB  - Injury to epidermis and other stratified epithelia triggers profound but
      transient changes in the pattern of keratin expression. In postmitotic cells
      located at the wound edge, a strong induction of K6, K16, and K17 synthesis
      occurs at the expense of the keratins produced under the normal situation. The
      functional significance of these alterations in keratin expression is not known.
      Here, we report that overexpression of a wild-type human K16 gene in a tissue
      specific fashion in transgenic mice causes aberrant keratinization of the hair
      follicle outer root sheath and proximal epidermis, and it leads to
      hyperproliferation and increased thickness of the living layers (acanthosis), as
      well as cornified layers (hyperkeratosis). The pathogenesis of lesions in
      transgenic mouse skin begins with a reorganization of keratin filaments in
      postmitotic keratinocytes, and it progresses in a transgene level-dependent
      fashion to include disruption of keratinocyte cytoarchitecture and structural
      alterations in desmosomes at the cell surface. No evidence of cell lysis could be
      found at the ultrastructural level. These results demonstrate that the disruption
      of the normal keratin profile caused by increased K16 expression interferes with
      the program of terminal differentiation in outer root sheath and epidermis. They
      further suggest that when present at sufficiently high intracellular levels, K16,
      along with K6 and K17, appear capable of inducing a reorganization of keratin
      filaments in the cytoplasm of skin epithelial cells.

PMID- 7523424
TI  - Tumor cells secrete an angiogenic factor that stimulates basic fibroblast growth
      factor and urokinase expression in vascular endothelial cells.
AB  - Culture medium conditioned by human SK-Hep1 hepatoma cells or mouse S180 sarcoma
      cells rapidly up-regulates endothelial cell expression of basic fibroblast growth
      factor (bFGF) and induces formation of capillary-like structures by vascular
      endothelial cells grown on three-dimensional fibrin gels (in vitro angiogenesis).
      Incubation of endothelial cells with the tumor cell-conditioned media also
      results in increased expression of urokinase plasminogen activator (uPA), a key
      component of the proteolytic system required for cell invasion and capillary
      formation. Although the tumor cell-conditioned media contain no bFGF, addition of
      anti-recombinant bFGF IgG abolishes the up-regulation of uPA and blocks in vitro
      angiogenesis. This indicates that both the increase in uPA production and
      formation of capillary-like structures are mediated by endogenous bFGF expressed
      by the endothelial cells. Both the bFGF/uPA-inducing activity and the angiogenic
      activity of SK-Hep1 cell-conditioned medium copurify with a relatively acid
      resistant peptide that has moderate affinity for heparin and M(r) < 18 kDa > 3.5
      kDa. Known cytokines with similar biochemical features do not possess the same
      biological activity. These findings indicate that angiogenesis can be mediated by
      endothelial cell bFGF through an autocrine mechanism and that the bFGF-inducing
      peptide may represent a novel tumor-derived angiogenic factor that modulates in
      endothelial cells the concerted expression of cytokines and proteolytic enzymes
      required for capillary formation.

PMID- 7523425
TI  - Enhanced expression of dihydrofolate reductase by bovine kidney epithelial cells
      results in altered cell morphology, IGF-I responsiveness, and IGF binding protein
      3 expression.
AB  - The kidney epithelial cell line (MDBK) secretes primarily insulin-like growth
      factor binding protein (IGFBP)-2 under basal conditions, but exposure to
      forskolin decreases the synthesis of and induces IGFBP-3. Since IGFBP-3 has been
      shown to both potentiate and inhibit insulin-like growth factor (IGF)
      bioactivity, MDBK cells were transfected with an expression vector containing
      bovine IGFBP-3 cDNA and the dihydrofolate reductase (DHFR) gene as a selectable
      marker, with the goal of obtaining an epithelial cell line which constitutively
      secreted IGFBP-3. Stable clones which secreted greater than 100 ng/ml of IGFBP-3
      were obtained and designated MDBKpMONBP-3. Northern blotting indicated that
      endogenous IGFBP-3 mRNA, which was undetectable in wild-type (WT) MDBK cells, was
      expressed in MDBKpMONBP-3 cells while the IGFBP-3 transgene did not appear to be
      expressed. DHFR mRNA transcripts were also expressed by MDBKp-MONBP-3 cells,
      whereas these transcripts were not detected in WT MDBK cells, suggesting that
      gene amplification of DHFR may have allowed cells to survive in methotrexate
      (MTX) without taking up the expression vector. In addition to the altered pattern
      of IGFBP-3 secretion, a marked alteration in cell morphology was observed.
      MDBKpMONBP-3 cells grew in distinct islands and exhibited dome formation (a
      characteristic of differentiated epithelial cells) whereas the WT cells did not.
      The alterations in morphology and IGFBP-3 expression were irreversible, since
      MDBKpMONBP-3 cells failed to revert to the WT phenotype upon removal of MTX and
      dialyzed serum. Since vectorial secretion of proteins is often associated with
      epithelial cell differentiation, cells were plated on tissue culture inserts
      which allowed conditioned media (CM) to be collected from both the apical and
      basal surfaces of confluent monolayers. Release of IGFBP-2 was approximately
      equal from apical and basal surfaces in WT MDBK cells. In contrast, release of
      both IGFBP-2 and IGFBP-3 was greater (3.1-fold and 3.5-fold, respectively) from
      basal as compared to apical surfaces of the MDBKpMONBP-3 cells. To determine if
      cells which were secreting IGFBP-3 had altered growth responses to IGF-I, cells
      were grown in serum-free media in the presence of IGF-I (0 to 100 ng/ml).
      Treatment of MDBKpMONBP-3 cells with 100 ng/ml of IGF-I increased cell number 138
      +/- 37% above serum-free controls compared to 73 +/- 10% in WT MDBK
      cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523423
TI  - Expression of beta 1B integrin isoform in CHO cells results in a dominant
      negative effect on cell adhesion and motility.
AB  - The integrin subunit beta 1B, a beta 1 isoform with a unique sequence at the
      cytoplasmic domain, forms heterodimers with integrin alpha chains and binds
      fibronectin, but it does not localize to focal adhesion sites (Balzac, F., A.
      Belkin, V. Koteliansky, Y. Balabanow, F. Altruda, L. Silengo, and G. Tarone.
      1993. J. Cell Biol. 121:171-178). Here we analyze the functional properties of
      human beta 1B by expressing it in hamster CHO cells. When stimulated by specific
      antibodies, beta 1B does not trigger tyrosine phosphorylation of a 125-kD
      cytosolic protein, an intracellular signalling pathway that is activated both by
      the endogenous hamster or the transfected human beta 1A. Moreover, expression of
      beta 1B results in reduced spreading on fibronectin and laminin, but not on
      vitronectin. Expression of beta 1B also results in severe reduction of cell
      motility in the Boyden chamber assay. Reduced cell spreading and motility could
      not be accounted for by preferential association of beta 1B with a given integrin
      alpha subunit. These data, together with our previous results, indicate that beta
      1B interferes with beta 1A function when expressed in CHO cells resulting in a
      dominant negative effect on cell adhesion and migration.

PMID- 7523427
TI  - Modulation of scatter factor/hepatocyte growth factor activity by cell-substratum
      adhesion.
AB  - Scatter factor/hepatocyte growth factor (SF/HGF) is a multifunctional growth and
      motility factor whose activities vary with cell type. Here, the composition of
      the substratum was found to profoundly alter the scattering activities of SF/HGF,
      but not its mitogenetic effects, in MDCK cells. Whereas enhancement of DNA
      synthesis and induction of cell flattening by SF/HGF were independent of
      substratum composition (i.e. occurred on both fibronectin and vitronectin
      surfaces), colony dispersion as a result of cell separation fails to occur or is
      markedly reduced on surfaces where vitronectin is the major adhesive ligand.
      Prolonged exposure of non-scattering cultures to SF/HGF resulted in cells at
      colony margins producing long protrusions, which indicate that the motility of
      these cells is stimulated but 'frustrated' by the lack of breakdown of cell-cell
      adhesion. Scattering therefore appears to comprise two major components:
      increased motility and breakdown of cell-cell adhesion. The pathway leading to
      the breakdown of cell-cell contacts is modulated by downstream signals from
      extracellular matrix receptors. When cultured on immobilised fibronectin,
      vitronectin or a surface containing both, colony dissociation correlates with the
      presence of fibronectin, suggesting that positive signals from fibronectin
      receptors are required for SF/HGF-induced cell separation. Comparison of the
      findings in this study with those of a recent report on the modulation of SF/HGF
      induced tubulogenesis by ECM (Santos, O. F. P. and Nigam, S. K. (1993) Dev. Biol.
      160, 293-302), where vitronectin in type-1 collagen gels alters the pattern of
      SF/HGF-induced MDCK tubule formation from highly branched to long and unbranched,
      suggests that cell motility enhancement leads to tubule formation whereas the
      breakdown of cell-cell adhesion is required for tubule branching.

PMID- 7523426
TI  - Immuno-EM localization of the beta 1 integrin subunit in wet-cleaved fibronectin
      adherent fibroblasts.
AB  - Using immuno-EM, we have studied the distribution of the beta 1 integrin subunit
      in chicken embryo fibroblasts allowed to adhere and spread for 3 hours on a
      fibronectin-coated surface in serum-free medium. The cells were wet-cleaved,
      which removed most of the cell body, yielding ventral plasma membranes with
      little, and sometimes virtually no, associated cytoskeleton. The beta 1 integrin
      subunit was detected with antibodies against the cytoplasmic domain. In immune
      fluorescence, it colocalized with adhesion plaques, in a punctate staining
      pattern, and often seemed to be at the periphery of the plaque. By immuno-EM,
      beta 1 was in fact found in discrete clusters, not throughout the plaque. In deep
      cleaved cells from which virtually all cytoskeleton was removed, clusters could
      often be seen to be located on fibronectin fibrils. Furthermore, beta 1 was
      present in clusters at the cell margins, and isolated or in small groups at the
      very edge of the cell. When fibronectin synthesis, and consequently fibril
      formation, was inhibited by cycloheximide, large adhesion plaque-like structures
      were formed at the cell margin. This phenotype was reversed by addition of
      soluble fibronectin, which was incorporated into fibrils. As in normal plaques,
      talin and vinculin were present, the plasma membrane was very close (10-20 nm) to
      the substratum and the fibronectin layer underneath was removed. These plaques
      did contain beta 1 integrins but they were not in clusters. These observations
      indicate that the talin-vinculin network of an adhesion plaque is normally
      anchored to the substratum at discrete beta 1 integrin clusters that may be
      located on fibronectin fibrils, and that elsewhere the plaque is not necessarily
      attached to the substratum by interaction of integrins with matrix proteins. In
      the absence of fibronectin fibrils, adhesion plaque-like structures can be
      formed, but these are aberrant in size, location and fine structure.

PMID- 7523428
TI  - Different pial arteriolar responses to acetylcholine in the newborn and juvenile
      pig.
AB  - Using the closed cranial window technique, the present study was designed to test
      the hypothesis that the pial arteriolar response to acetylcholine is age
      dependent. In newborn pigs (1-5 days old) pretreated with the phosphodiesterase
      inhibitor isobutyl methyl xanthine (IBMX), acetylcholine (10(-5) M) produced pial
      arteriolar constriction with no change in CSF cyclic GMP (cGMP) that was blocked
      by indomethacin (5 mg/kg i.v.). In contrast, in indomethacin- and IBMX-treated
      juvenile pigs (3-4 weeks old), acetylcholine (10(-) M) increased the pial
      arteriolar diameter by 17 +/- 1% and increased CSF cGMP by 2.1 +/- 0.3-fold.
      Similar vascular and biochemical changes for acetylcholine were observed in
      juvenile pigs pretreated with only IBMX. In the absence of IBMX, acetylcholine
      produced modest pial constriction in juvenile pigs. In the IBMX-pretreated
      juvenile pigs, L-nitroarginine (LNA; 10(-6) M) decreased pial arteriolar diameter
      by 15 +/- 2% and blocked acetylcholine-induced dilation and associated changes in
      CSF cGMP. A23187, a calcium ionophore, and sodium nitroprusside (SNP) elicited
      similar dilation and changes in CSF cGMP in both age groups. LNA blocked A23187
      dilation, but SNP dilation was unchanged. L-Arginine (10(-3) M) partially
      restored acetylcholine- and A23187-induced dilation to indomethacin- and LNA
      pretreated juvenile pigs. These data show that acetylcholine produces dilation in
      the juvenile pig through the production of the putative endothelium-derived
      relaxing factor (EDRF) nitric oxide but does not do so in the new born period. We
      speculate that contributions of EDRF to the acetylcholine-induced changes in pial
      arteriolar diameter develop with age.

PMID- 7523429
TI  - Angiotensin IV reverses the acute cerebral blood flow reduction after
      experimental subarachnoid hemorrhage in the rat.
AB  - The effect of angiotensin (ANG) IV on CBF after experimental subarachnoid
      hemorrhage (SAH) was studied in rats using laser-Doppler flowmetry. ANG IV (1
      microgram/kg/min i.v.) or saline treatments were started 20 min after SAH. ANG IV
      increased CBF (from 45 to 84% of baseline) by 60 min. In the saline group, CBF
      remained low (51%). Pretreatment with the specific ANG II antagonist Sar1, Ile8
      ANG II did not antagonize ANG IV. Determination of nitric oxide synthase (NOS)
      activity in vitro or inhibition of NOS in vivo did not support a role for NO in
      the action of ANG IV.

PMID- 7523430
TI  - The NOS inhibitor, 7-nitroindazole, decreases focal infarct volume but not the
      response to topical acetylcholine in pial vessels.
AB  - We examined whether 7-nitroindazole (7-NI), a putative inhibitor of neuronal
      nitric oxide synthase (nNOS), decreases cerebral infarction 24 h after proximal
      middle cerebral artery (MCA) occlusion. In preliminary experiments, we determined
      that 7-NI (25, 50, and 100 mg/kg i.p.) decreased nitric oxide synthase (NOS)
      activity within cerebral cortex by 40-60% when measured up to 120 min, but not
      240 min after administration. At 25 or 50 mg/kg, 7-NI did not alter the systemic
      arterial blood pressure or the dilation of pial arterioles after topical
      acetylcholine (10 and 100 microM). To examine the effect of 7-NI on infarct size,
      55 Sprague-Dawley halothane-anesthetized rats were subjected to proximal MCA
      occlusion (modified Tamura method). Five minutes after occlusion, 7-NI (25 or 50
      mg/kg i.p.) or vehicle was injected. Animals treated with 25 or 50 mg/kg showed
      25 and 27% reductions in infarct volume, respectively. Coadministration of L
      arginine (300 mg/kg i.p.) plus 7-NI (25 mg/kg i.p.) reversed the effect. If,
      indeed, the effects of 7-NI are mediated by inhibition of nNOS activity, these
      results suggest that enzymatic products of the neuronal isoform promote ischemic
      injury and that they do so at least within the first few hours after permanent
      occlusion. The results also emphasize the importance of developing strategies to
      selectively inhibit the neuronal isoform inasmuch as we observed previously that
      administering the less selective NOS inhibitor, N omega-nitro-L-arginine (L-NA),
      in the same model either caused no change or increased the volume of ischemic
      injury.

PMID- 7523431
TI  - Distribution of nitric oxide synthase in the human cerebral blood vessels and
      brain tissues.
AB  - The distribution of nitric oxide synthase was investigated in human cerebral
      blood vessels and brain tissues. NADPH-diaphorase histochemistry, which is a
      marker for nitric oxide synthase in neurons and endothelial cells, revealed
      periadventitial nerve fibers in the arteries of the circle of Willis and their
      cortical branches, as well as the common carotid and subclavian arteries. The
      fibers were mostly nonvaricose in the periadventitial nerve trunk and were
      varicose within the adventitia. Patchy reaction products were distributed in the
      perinuclear region of each endothelial cell. Smooth muscle cells in the tunica
      media were weakly stained. Staining was particularly intense in regions with
      atherosclerotic changes, which consist of macrophage infiltration and
      proliferation of fibroblasts. In the neural parenchyma, two types of NADPH
      diaphorase reactive neurons were differentiated. Type I neurons were intensely
      stained, medium-sized, and bipolar or multipolar. They were distributed in the
      cerebral cortex and white matter, mostly in the subcortical white matter. Type II
      neurons were lightly stained, small oval neurons with fine processes and were
      distributed in the cerebral cortex. Endothelial cells were intensely reactive for
      NADPH-diaphorase in the arteries, arterioles, and capillaries but weakly in
      veins. Immunohistochemistry for neural nitric oxide synthase labeled perivascular
      nerves in the larger arteries and those in the neural parenchyma. Both type I and
      type II neurons were labeled. Nitric oxide synthase in endothelial cells and the
      nerve encircling blood vessels further suggests a dual control of cerebral
      circulation by nitric oxide in human brain.

PMID- 7523432
TI  - Cerebral blood flow changes during cortical spreading depression are not altered
      by inhibition of nitric oxide synthesis.
AB  - CBF increases concomitantly with cortical spreading depression (CSD). We tested
      the hypothesis that CBF changes during CSD are mediated by nitric oxide (NO).
      Male Wistar rats (n = 23) were subjected to KCl-induced CSD before and after
      administration of nitric oxide synthase (NOS) inhibitors N-nitro-L-arginine (L
      NNA) or N-nitro-L-arginine methyl ester (L-NAME) and in nontreated animals. CBF,
      CSD, and mean arterial blood pressure were recorded. Brain NOS activity was
      measured in vitro in control, L-NNA, and L-NAME-treated rats by the conversion of
      [3H]arginine to [3H]citrulline. Our data show that the NOS inhibitors did not
      significantly change regional CBF (rCBF) during CSD, even though cortical NOS
      activity was profoundly depressed and systemic arterial blood pressure was
      significantly increased. Our data suggest that rCBF during CSD in rats is not
      regulated by NO.

PMID- 7523433
TI  - Antibody response against three epitopic domains on human chorionic gonadotropin
      (hCG) in women and rodents immunized with a beta hCG-based immunocontraceptive
      vaccine.
AB  - The antibody repertoire generated against human chorionic gonadotropin (hCG),
      following immunization with an immunocontraceptive vaccine based on the beta
      subunit of the hormone, in humans was compared with that generated in rats. Three
      epitopic domains represented by the beta hCG loop peptide 38-57, the carboxy
      terminal peptide (CTP) 109-145, and a region defined by monoclonal antibody (MAb)
      206 were probed. In both species, the titer of antibodies against the MAb 206
      defined epitopic domain had a good correlation with the total anti-hCG antibody
      titers. However, the antibody response against the beta hCG loop peptide (38-57)
      was not observed in human subjects and there was a weak response against this
      peptide in rats. Despite the good anti-hCG antibody titers in all animals (n =
      8), only two had antibodies against this domain. A good antibody response was
      observed against CTP in rats, whereas in humans this region was weakly
      immunogenic. Antibodies against CTP were detected in random samples in only 57%
      of the subjects and this response had no correlation with the total anti-hCG
      antibody titers. The high antibody response against CTP in rodents compared to
      humans may be due to its recognition as a foreign determinant. Our results
      demonstrate that contraception can be achieved in women despite a poor antibody
      response against the CTP (109-145) and a receptor binding domain (38-57) of beta
      hCG.

PMID- 7523434
TI  - Modulation of immunoglobulin production and cytokine mRNA expression in
      peripheral blood mononuclear cells by intravenous immunoglobulin.
AB  - Intravenous immunoglobulin (IVIG) has the potential to regulate Ig production,
      but the mechanism(s) responsible for this effect is unknown. In experiments
      reported here, we examined the ability of IVIG to regulate Ig production in human
      peripheral blood mononuclear cells (PBMCs) stimulated with pokeweed mitogen
      (PWM). IVIG (2-10 mg/ml) showed a potent (80-85%) inhibition of PWM-stimulated
      IgG, IgM, and IgA production. To determine more precisely how IVIG mediated the
      inhibition of Ig production, we studied Ig promoting cytokine gene expression
      after PWM stimulation with or without IVIG (2 and 10 mg/ml) using dot-blot
      techniques. RNA was isolated from PBMCs at predetermined time points and probed
      with cDNAs specific for human cytokines (IL-1 beta, IL-2, IL-2R, IL-4, IL-5, IL
      6, gamma-IFN, and TNF-alpha). IL-6 mRNA accumulation was maximal at 4.5 hr post
      PWM stimulation and was inhibited 64-75% when IVIG (10 mg/ml) was present. gamma
      IFN mRNA levels peaked at 72 hr poststimulation and were also 68-75% inhibited by
      IVIG. IL-2 mRNA levels peaked at 4.5 hr and were 23-46% inhibited by IVIG. The
      inhibitory effect of IVIG on production of these cytokines (IL-6 and gamma-IFN)
      was also observed at the protein level in sonicated PBMCs after incubation with
      PWM and IVIG. The mRNA levels for other cytokines were not or only minimally
      inhibited by IVIG. Addition of IL-6, gamma-IFN, or IL-2 partially restored Ig
      production in IVIG-treated PWM-stimulated cultures, suggesting that inhibition of
      other cytokines or another mechanism(s) independent of cytokine inhibition might
      also be involved, although inhibition of IL-6, gamma-IFN, and IL-2 may be one of
      the critical factors in the suppression of Ig production by IVIG.

PMID- 7523435
TI  - Optimizing the effectiveness of hematopoietic growth factors.
AB  - Hematopoiesis is regulated in a very precise fashion by a balance between both
      positive and negative growth factor signals in the hematopoietic
      microenvironment. Many of these growth factor signals have been identified and
      are available as recombinant proteins. At the present time, the approved uses for
      hematopoietic growth factors involve their use to facilitate blood cell
      production in situations of hematopoietic suppression or in cases where
      endogenous growth factor production is inappropriately low. Recent studies with
      the hematopoietic growth factors are looking at innovative strategies for their
      use and new clinical situations in which to evaluate their effectiveness. This
      review looks at some of these new uses for hematopoietic growth factors.

PMID- 7523436
TI  - Effects of persistent chlorinated hydrocarbons on reproductive tissues in female
      rabbits.
AB  - The female rabbit was used to study (i) accumulation of lipophilic chlorinated
      hydrocarbons in genital tract tissues and (ii) subsequent morphological and
      functional effects after long-term low-dose exposure. Polychlorinated biphenyl
      (PCB), 1,1-di(p-chlorophenyl)-2,2,2-trichloroethane (DDT) and gamma
      hexachlorocyclohexane (gamma-HCH) (dosages: 4, 3 and 0.8 mg per kg body weight,
      respectively) and a combination of these three components (and dosages) were
      administered to sexually mature rabbits over a period of 12-15 weeks. The animals
      were killed shortly before and at various times after ovulation. Accumulation of
      chlorinated hydrocarbons was high in ovarian, oviductal and uterine tissues, in
      follicular fluid and clearly detectable in uterine secretions. In follicular
      fluid, the concentration and patterns of congeners and isomers of PCB and DDT
      were distinctly different from serum. DDT- and gamma-HCH-treated animals showed a
      significantly reduced ovulation rate (P < 0.002 and 0.05, respectively). During
      early pregnancy DDT decreased serum progesterone levels and changed the protein
      pattern of uterine secretion. Functional effects, however, were much less
      expressed compared with the highly significant accumulation of the persistent
      organochlorines in the genital tract.

PMID- 7523437
TI  - Uterine endocrinology and paracrinology: insulin-like growth factor binding
      protein-1 and placental protein 14 revisited.
AB  - A large number of proteins and peptides have been identified in the endometrium
      where they are likely to exert local biological effects. These substances may be
      enzymes, their inhibitors, proteinases, proteinase inhibitors, hormones, or
      bioactive peptides with diverse functions. Endometrial function and embryo
      endometrial interactions require synchronized actions between endocrine and local
      factors. As examples of local factors recent studies on the insulin-like growth
      factor (IGF) system and placental protein 14 (PP14) are reviewed. IGF binding
      protein-1 (IGFBP-1) and PP14 are products of the secretory phase endometrium:
      IGFBP-1 is produced by decidualized stromal cells and PP14 by glandular
      epithelial cells. IGFBP-1 may inhibit the action of IGFs at the endometrial
      trophoblastic interphase, and it may also have a role in stromal-epithelial
      interaction. PP14 has immunosuppressive properties, and recent findings indicate
      that it may play a part in the fertilization process by inhibiting binding of
      spermatozoa to the zona.

PMID- 7523438
TI  - Competitive inhibition enzyme-linked immunosorbent assay for antibody in sheep
      and other ruminants to a conserved epitope of malignant catarrhal fever virus.
AB  - Malignant catarrhal fever (MCF) is a severe, usually fatal, acute systemic
      disease syndrome of certain domestic and wild ruminants caused by members of the
      family Gammaherpesvirinae. Two distinct but closely related viruses cause
      clinically indistinguishable syndromes: one that is indigenous to the widebeest
      and the other that apparently is indigenous to domestic sheep. Neither the
      pathogenesis nor the epidemiology of sheep-associated MCF (SA-MCF) is understood,
      primarily because of a lack of adequate detection methods for the etiologic agent
      or antibody against it. No acceptably documented isolates of SA-MCF virus have
      been reported, and existing antibody assays suffer from significant cross
      reactivity with other viruses. As a basis for a specific serologic assay, an
      attempt was made to identify an epitope conserved among all isolates of MCF
      viruses, by using a monoclonal antibody (MAb) produced against a previously
      reported U.S. isolate of MCF virus. A MAb (15-A) which bound a conserved epitope
      present on all four isolates of MCF virus examined was found. MAb 15-A did not
      react with eight common sheep and goat viruses or five common bovine viruses.
      Immunoprecipitation revealed that the 15-A epitope was located on the viral
      glycoprotein complex, with molecular masses of 115, 110, 105, 78, and 45 kDa.
      Sera from experimentally and naturally infected animals which yielded a similar
      glycoprotein complex immunoprecipitation pattern competed with MAb 15-A for its
      epitope. A competitive inhibition enzyme-linked immunosorbent assay (ELISA) based
      on MAb 15-A was therefore developed. The assay detected antibody in inapparently
      infected sheep and in cattle, deer, and bison with clinical MCF. Of the 149 serum
      samples from sheep associated with MCF outbreaks, 88 (55%) were seropositive by
      competitive inhibition ELISA.

PMID- 7523439
TI  - Detection of microsporidial spores in fecal specimens from patients diagnosed
      with cryptosporidiosis.
AB  - Patients infected with Cryptosporidium parvum may have concurrent infections with
      microsporidia. Two modified trichrome stains and a polyclonal indirect
      fluorescent-antibody procedure were used for the detection of microsporidia; the
      Merifluor Cryptosporidium-Giardia monoclonal direct immunofluorescence detection
      kit was used for the detection of C. parvum. Formalinized stool specimens from 60
      immunocompromised patients strongly suspected of having or previously diagnosed
      with cryptosporidiosis or microsporidiosis were examined. All patients were
      positive for one or both parasites, 18 (30%) with C. parvum only, 25 (42%) with
      microsporidia only, and 17 (28%) with both C. parvum and microsporidia. These
      findings emphasize the importance of considering both organisms as potential
      causative agents of diarrhea in compromised patients.

PMID- 7523440
TI  - Distinct genotypes of human and canine isolates of Campylobacter upsaliensis
      determined by 16S rRNA gene typing and plasmid profiling.
AB  - The utility of combined 16S rRNA (rrs) gene restriction fragment length
      polymorphism and plasmid profiles to differentiate between and within
      Campylobacter upsaliensis of human and canine origin was examined. Fourteen
      distinct rrs gene restriction fragment length polymorphs consisting of bands
      sized between 1.9 and 4.8 kb were observed. The copy number of the 16S rRNA gene
      was three in most strains of C. upsaliensis. Plasmids were found in almost 60% of
      the strains; ranging in size from 1.5 to 100 kb, they gave 15 distinct plasmid
      profiles. All isolates from humans contained one or more plasmids, as did strains
      isolated from dogs with sporadic diarrhea. The two commonest 16S ribotypes were
      divided into eight and nine subgroups by plasmid profiling. The genotyping of
      canine isolates from three veterinary surveys detected both multiple infections
      and reinfection of dogs. Except for one, each of the isolates from humans
      constituted a single and unique 16S ribotype, and these more frequently carried
      plasmids than did canine strains. Ribotypes of human strains were not found among
      canine isolates. These results suggest that host-specific genotypic differences
      may exist among strains of C. upsaliensis, for example, intraspecific clones or
      clone complexes pathogenic for humans.

PMID- 7523441
TI  - Characterization and presumptive identification of Helicobacter pylori isolates
      from rhesus monkeys.
AB  - We characterized 38 Helicobacter isolates, including 22 from gastric biopsy
      samples obtained from 14 rhesus monkeys and single isolates from 16 monkeys in a
      different colony. Biochemical profiles of these isolates were nearly identical to
      that of Helicobacter pylori ATCC 43504. Restriction fragment length polymorphism
      (RFLP) analysis indicated that each infected monkey harbored one to four strains.
      The 17 RFLP types found among these 22 isolates differed from all seven RFLPs
      found among the other 16 isolates. Thus, monkeys within a given colony are more
      likely to be infected by Helicobacter isolates with the same or a similar RFLP
      than are monkeys from different colonies. A 16S rRNA gene was amplified by PCR
      and cloned from the Helicobacter isolate from rhesus monkey 85D08. Ribotyping
      with this probe demonstrated less diversity among isolates from rhesus monkeys
      than was reported among isolates of H. pylori from humans, as did RFLP analysis
      of a PCR fragment of the ureA-ureB gene cluster. The DNA sequence of the cloned
      16S rRNA gene was determined and compared with sequences reported for H. pylori
      and other Helicobacter species. Our analysis of 127 nucleotides (corresponding
      with residues 1240 to 1366 of the Escherichia coli 16S rRNA gene) indicated that
      the Helicobacter isolate from monkey 85D08 was 99.2 to 100% homologous to
      isolates of H. pylori from humans but only 83.5 to 96.9% homologous with other
      Helicobacter species in this region of the 16S rRNA gene. These data provide
      strong support for the presumptive identification of these isolates as H. pylori.

PMID- 7523442
TI  - Prostaglandins and inhibitors of arachidonate metabolism suppress experimental
      allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory
      disease of the central nervous system (CNS). It is an animal model of post
      infectious encephalomyelitis and multiple sclerosis (MS). Acute EAE is mediated
      by macrophages and by T helper 1 (Th1) lymphocytes directed against brain
      antigens. Inflammation in EAE could potentially be modified by prostaglandins
      (PG) secreted by blood monocytes (Mo) and brain glial cells. PGE elevates cAMP,
      which inhibits Mo function and selectively blocks secretion of cytokines by Th1
      cells. In the present study, we found that a long-acting PGE1 analogue (LAPGE)
      inhibited clinical and histological EAE. Indomethacin (INDO) also suppressed
      active EAE. The combination of INDO plus LAPGE inhibited disease further,
      possibly by allowing LAPGE to function unopposed by immunostimulatory PG. EAE was
      suppressed when these agents were administered from the time of immunization or
      from the onset of clinical disease. The combination of INDO plus LAPGE also
      inhibited delayed-type hypersensitivity (DTH) reactions to myelin basic protein
      (MBP), and diminished in vitro lymphocyte responses to mitogens and MBP. PGE
      analogues and modifiers of arachidonate metabolism block autoimmune responses to
      brain antigens in vitro and in vivo, and may ameliorate inflammatory and
      autoimmune diseases of the brain and other organs.

PMID- 7523443
TI  - Expression of ICAM-1, VCAM-1, L-selectin, and leukosialin in the mouse central
      nervous system during the induction and remission stages of experimental allergic
      encephalomyelitis.
AB  - Adhesion molecules facilitate infiltration of leukocytes into the central nervous
      system (CNS) of mice with experimental allergic encephalomyelitis (EAE).
      Expression of the adhesion molecules ICAM-1 (CD54), VCAM-1 (CD106), L-selectin
      (CD62L), and leukosialin (CD43) was analyzed via immunocytochemistry 4-28 days
      after the injection of encephalitogen into EAE-susceptible SWXJ mice.
      Constitutive ICAM-1 expression on large-diameter CNS vessels was upregulated on
      post-injection days 8, 11, 14 and 18 (concurrent with de novo expression on
      smaller capillaries and glial cells), partially downregulated by day 23, and back
      to control levels by day 28. Constitutive VCAM-1 expression was upregulated by
      day 14 and back to control levels by day 28. Upregulation of ICAM-1 temporally
      coincided with the immigration of CD4+ lymphocytes and L-selectin+ leukocytes
      into the CNS, while downregulation coincided with their emigration. The
      infiltration of CD43+ leukocytes also coincided with the upregulation of vascular
      adhesion molecules, but CD43+ cells remained in the CNS after ICAM-1 and VCAM-1
      had returned to control levels. Cellular infiltration and adhesion-molecule
      expression preceded EAE clinical symptoms by a minimum of 3 days, suggesting a
      causal role of adhesion molecules in the initiation of CNS inflammation. However,
      prophylactic injections of monoclonal antibodies against either ICAM-1, L
      selectin, or CD43, did not ameliorate the clinical severity of EAE in this model.

PMID- 7523444
TI  - Exogenous tat protein activates central nervous system-derived endothelial cells.
AB  - Tat protein, an HIV gene product known to be secreted extracellularly, was tested
      to determine its role in the dissemination of HIV into the central nervous system
      (CNS). Tat was shown to activate human CNS-derived endothelial cells (CNS-EC) by
      the increase in the expression of E-selectin, the synthesis of IL-6, and the
      secretion of plasminogen activator inhibitor-1 (PAI-1). Tat also functioned
      synergistically with tumor necrosis factor alpha (TNF). AIDS brains stained for
      tat in situ, demonstrated positive cells. These data suggest that secreted tat
      protein may increase leukocyte binding, and alter the blood-brain barrier
      permeability to enhance dissemination of HIV-infected cells into the CNS.

PMID- 7523445
TI  - T lymphocyte recognition sites on peripheral nerve myelin P0 protein.
AB  - Synthetic peptides corresponding to the extracellular and cytoplasmic domain of
      bovine (b) or rat (r) peripheral myelin P0 protein were used to establish a total
      of 50 short-term T cell lines (TCL) from blood of eight healthy subjects. Despite
      expressing different HLA-DR and HLA-DQ specificities, one or more TCL (range 1
      16) specific for peptide bovine P0 19-38 could be isolated from the blood of each
      donor. Therefore, this peptide covers an immunodominant T cell recognition site
      in humans. However, when testing seven bP0-19-38-specific TCL derived from blood
      of two healthy subjects for recognition of the corresponding human P0 sequence,
      no TCL showed any proliferative response. Bovine P0-19-38 differs in only two
      amino acid residues from the human peptide. This observation stresses the
      necessity for using homologous antigens when screening for T cell-mediated
      autoreactivity to myelin antigens in humans. Unexpectedly, we failed to establish
      a single P0 peptide-specific TCL from blood of four patients with acute Guillain
      Barre syndrome (GBS), in which P0 is considered a putative target autoantigen. As
      already suggested by others, this could indicate that T cell responses to P0 do
      not play a pathogenic role in all GBS cases. Alternatively, in these four
      patients neuritogenic P0-specific T lymphocytes may have been sequestrated to
      peripheral nerves.

PMID- 7523446
TI  - The intrathecal synthesis of virus-specific oligoclonal IgG in multiple
      sclerosis.
AB  - A highly sensitive antigen-mediated capillary blot technique was developed for
      the detection of virus-specific oligoclonal IgG in paired CSF and serum samples
      from patients with various neurological diseases. In multiple sclerosis,
      intrathecal synthesis of oligoclonal antibodies was present against measles
      (70%), rubella (60%), varicella zoster (40%) and mumps (30%); in most cases
      (75%), such synthesis involved two or more viruses. In contrast, antibodies
      against a non-neurotropic virus (cytomegalovirus) were rarely produced in CSF
      from MS patients (5%). However, this 'polyspecific' reaction was not restricted
      to MS samples but was also observed in neurolupus and in the late phase of
      infectious diseases of the central nervous system. These anti-viral antibodies
      could be produced without de novo replication of the corresponding viral genome
      and are likely mere bystanders of an ongoing immune response.

PMID- 7523447
TI  - Adoptive transfer of experimental allergic encephalomyelitis: recipient response
      to myelin basic protein-reactive lymphocytes.
AB  - We have used adoptive transfer of myelin basic protein (MBP)-reactive lymphocytes
      in the Lewis rat model of experimental allergic encephalomyelitis (EAE) to
      identify stages of effector cell development and to investigate the nature of the
      subsequent recipient response to the transferred cells. Depending on the timing
      of cell collection, lymph node cells (LNC) obtained from MBP-CFA (MBP emulsified
      in complete Freund's adjuvant)-immunized donors may directly transfer clinical
      disease; however, independent of disease development, recipients of LNC develop
      early onset of clinical disease following immunization of the recipients with MBP
      CFA, consistent with the presence of MBP-memory cells in the LNC transfer
      inoculum. Similarly obtained spleen cells do not directly transfer disease and do
      not contain MBP-memory cells (as defined by the early onset of clinical disease
      following MBP-CFA challenge). Spleen cells adoptively transfer clinical disease
      only following in vitro culture stimulation with antigen or selected mitogens.
      Recipients of the primary culture-derived encephalitogenic spleen cells also
      develop an accelerated onset of clinical disease following MBP-CFA challenge,
      indicative of the presence of MBP-memory cells, and are not vaccinated.
      Encephalitogenic T cell lines adoptively transfer clinical disease, and in most
      cases recipients are vaccinated to MBP-CFA-induced active disease, but remain
      susceptible to adoptively transferred disease. Co-transfer of encephalitogenic T
      cell line cells with MBP-reactive lymph node or encephalitogenic spleen cells
      does not alter the vaccination response. We have found that during the process of
      T cell line development, the vaccinating phenotype is acquired following the
      second antigen stimulation cycle. These studies also demonstrate that regulation
      induced by T cell vaccination blocks the development of effector cells from
      precursor cells and that such regulation is also equally effective in blocking
      disease development in recipients which have increased numbers of memory cells.
      Thus, the response to T cell vaccination, once established, is fully capable of
      inhibiting the development of effector cells from increased numbers of
      precursor/memory cells, a response that would be needed in the clinical
      application of vaccination-induced resistance.

PMID- 7523448
TI  - Hyper IgM syndrome: two mutations distinguish HIM.

PMID- 7523449
TI  - Hyper IgM syndrome associated with defective CD40-mediated B cell activation.
AB  - Recent studies show that most patients with X-linked hyper IgM syndrome have
      defects in the gene for CD40 ligand. We evaluated 17 unrelated males suspected of
      having X-linked hyper IgM syndrome. Activated T cells from 13 of the 17 patients
      failed to bind a soluble CD40 construct. In these patients, the sequence of CD40
      ligand demonstrated mutations. By contrast, T cells from the remaining four
      patients exhibited normal binding to the CD40 construct. Sequencing of the cDNA
      for CD40 ligand from these patients did not show mutations. The possibility that
      hyper IgM syndrome in these four patients was due to abnormalities in the B cell
      response to CD40-mediated signals was examined. Peripheral blood lymphocytes were
      stimulated with anti-CD40 alone, IL4 alone or anti-CD40 plus IL4. In comparison
      with B cells from controls or patients with hyper IgM syndrome and mutant CD40
      ligand, B cells from the patients with hyper IgM syndrome and normal CD40 ligand
      were defective in their ability to secrete IgE (P < 0.02) or express activation
      markers, CD25 and CD23 (P < 0.02) in response to stimulation with anti-CD40. The
      failure of these B cells to respond to CD40-mediated activation could not be
      attributed to a generalized deficiency in B cell activation because IL4 induced
      normal up-regulation of CD23 and CD25 expression. These findings indicate that
      hyper IgM syndrome may result from defects in expression of CD40 ligand by
      activated T cells or defects in CD40-mediated signal transduction in B cells.

PMID- 7523450
TI  - Diesel exhaust particles induce local IgE production in vivo and alter the
      pattern of IgE messenger RNA isoforms.
AB  - Diesel exhaust particles (DEP) have been implicated in the increased incidence of
      allergic airway disorders. We investigated the effects of DEP on localized
      immunoglobulin production by performing nasal challenges with varying doses of
      DEP and analyzing the local immune response in nasal lavages obtained before and
      after. A significant rise in nasal IgE but not IgG, IgA, IgM, or albumin was
      observed in subjects 4 d after challenge with 0.30 mg DEP, equivalent to exposure
      on an average Los Angeles day. Direct evidence for DEP-enhanced local production
      of IgE was that challenge increased the number of IgE-secreting cells in lavage
      fluid from < 1 in 2,000,000 to > 1 in 100,000 but did not alter the number of IgA
      secreting cells. There was a concomitant increase in epsilon mRNA production in
      the lavage cells. Additionally, DEP altered the relative amounts of five
      different epsilon mRNAs generated by alternative splicing, mRNAs that code for
      different IgE proteins. These results show that DEP exposure in vivo causes both
      quantitative and qualitative changes in local IgE production. The implication is
      that natural exposure to DEP may result in increased expression of respiratory
      allergic disease.

PMID- 7523451
TI  - The morphogenic/cytotoxic and prostaglandin-stimulating activities of interleukin
      1 beta in the rat ovary are nitric oxide independent.
AB  - Nitric oxide (NO) has been implicated as a mediator of physiologic and pathologic
      cellular injury. Since the cytokine interleukin-1 beta (IL-1 beta) induces nitric
      oxide synthase (NOS) activity as well as effects morphogenic/cytotoxic changes
      and increased prostaglandin (PGE2) levels in cultured whole ovarian dispersates,
      we set out to determine whether these actions are interrelated. Treatment with IL
      1 beta resulted in a marked increase in media nitrite and nitrate accumulation,
      morphological alterations, and increased release of lactate dehydrogenase (LDH)
      into media. Addition of IL-1 receptor antagonist (RA) eliminated these IL-1 beta
      effects. In contrast, specific inhibitors of NOS failed to reverse IL-1 beta
      induced morphogenic changes or LDH release in spite of complete reduction of
      media nitrite to control levels. Similarly, treatment with transforming growth
      factor beta 1, inhibited IL-1 beta-induced nitrite accumulation, but had no
      effect on the morphologic or cytotoxic endpoints. Moreover, the addition of
      sodium nitroprusside, an NO generator, resulted in progressive increments in
      media nitrite content without a corresponding increase in the IL-1 beta
      associated morphogenic changes or media LDH content. Furthermore, IL-1-induced
      PGE2 accumulation remained unaffected by specific NOS inhibition. These
      observations support the view that NO does not mediate the morphogenic/cytotoxic
      or inflammatory-like (e.g., PGE2 inducing) properties of IL-1 beta in cultured
      whole ovarian dispersates. Although the precise role of NO in ovarian physiology
      remains unknown, it is possible that NO participates in the periovulatory
      modulation of ovarian blood flow by virtue of its potent vasodilatory activity.

PMID- 7523452
TI  - Healthy subjects produce both anti-factor VIII and specific anti-idiotypic
      antibodies.
AB  - Anti-Factor VIII (FVIII) antibodies were prepared by a combination of salt
      precipitation, gel filtration chromatography, and specific adsorption over
      insolubilized FVIII from the serum of 10 healthy subjects with normal levels of
      FVIII. Antibody specificity was confirmed by the capacity to recognize soluble
      and insolubilized FVIII and to neutralize FVIII cofactor activity in FX
      activation. Epitope mapping was carried out using a competition ELISA in which
      affinity-purified human antibodies inhibited the binding of labeled monoclonal
      antibodies. In most cases, a single region of the A3 domain of the FVIII light
      chain was recognized by the antibodies, while the reactivity toward heavy chain
      epitopes differed from one antibody preparation to the other. Sera or IgG
      fractions of the serum before immunoadsorption over insolubilized FVIII did not
      bind to FVIII. The IgG fraction that was not retained on the FVIII immunosorbent
      contained IgG that bound to the variable part of anti-FVIII mouse monoclonal
      antibodies and inhibited the binding of labeled FVIII; in addition, the IgG
      fraction inhibited the binding of affinity-purified human antibodies to FVIII,
      thereby strongly suggesting the presence of anti-idiotypic antibodies. These
      findings indicate that the presence of anti-FVIII antibodies is a more universal
      phenomenon than previously thought and that anti-idiotypic antibodies capable of
      inhibiting the binding of anti-FVIII antibodies to FVIII are produced
      spontaneously.

PMID- 7523453
TI  - Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes.
      Central role of tumor necrosis factor-alpha.
AB  - Insulin resistance is an important metabolic abnormality often associated with
      infections, cancer, obesity, and especially non-insulin-dependent diabetes
      mellitus (NIDDM). We have previously demonstrated that tumor necrosis factor
      alpha produced by adipose tissue is a key mediator of insulin resistance in
      animal models of obesity-diabetes. However, the mechanism by which TNF-alpha
      interferes with insulin action is not known. Since a defective insulin receptor
      (IR) tyrosine kinase activity has been observed in obesity and NIDDM, we measured
      the IR tyrosine kinase activity in the Zucker (fa/fa) rat model of obesity and
      insulin resistance after neutralizing TNF-alpha with a soluble TNF receptor
      (TNFR)-lgG fusion protein. This neutralization resulted in a marked increase in
      insulin-stimulated autophosphorylation of the IR, as well as phosphorylation of
      insulin receptor substrate 1 (IRS-1) in muscle and fat tissues of the fa/fa rats,
      restoring them to near control (lean) levels. In contrast, no significant changes
      were observed in insulin-stimulated tyrosine phosphorylations of IR and IRS-1 in
      liver. The physiological significance of the improvements in IR signaling was
      indicated by a concurrent reduction in plasma glucose, insulin, and free fatty
      acid levels. These results demonstrate that TNF-alpha participates in obesity
      related systemic insulin resistance by inhibiting the IR tyrosine kinase in the
      two tissues mainly responsible for insulin-stimulated glucose uptake: muscle and
      fat.

PMID- 7523455
TI  - Measurement of free insulin-like growth factor-I using immunoradiometric assay.
AB  - The free Insulin-like growth factor-I (IGF-I) in plasma from normal adults was
      directly measured with a newly developed highly sensitive immunoradiometric assay
      (IRMA) for IGF-I. The capture antibody did not crossreact with IGF-I associated
      binding proteins which exist in plasma, and the assay was designed not to shift
      the equilibrium of the IGF-I and binding proteins. Total IGF-I concentration was
      measured using this assay with preliminary acid-ethanol extraction. Approximately
      1 percent of total IGF-I existed in the free form. Gel filtration of plasma was
      also used to separate the free IGF-I from its bound form. The free/total ratio of
      IGF-I as determined by gel filtration was similar to that determined directly by
      IRMA with and without acid-ethanol extraction.

PMID- 7523454
TI  - B lymphocyte binding to E- and P-selectins is mediated through the de novo
      expression of carbohydrates on in vitro and in vivo activated human B cells.
AB  - Cell adhesion to endothelium regulates the trafficking and recruitment of
      leukocytes towards lymphoid organs and sites of inflammation. This phenomenon is
      mediated by the expression of a number of adhesion molecules on both the
      endothelium and circulating cells. Activation of endothelial cells (EC) with
      different stimuli induces the expression of several adhesion molecules (E- and P
      selectins, ICAM-1, VCAM-1), involved in their interaction with circulating cells.
      In this report, we have studied the binding of nonactivated and activated B cells
      to purified E- and P-selectins. Activated but not resting B cells were able to
      interact with both selectins. This binding capacity of activated B cells
      paralleled the induction of different carbohydrate epitopes (Lewisx, sialyl
      Lewisx, CD57 and CDw65) as well as other molecules bearing these or related
      epitopes in myeloid cells (L-selectin, alpha L beta 2 and alpha X beta 2
      integrins, and CD35) involved in the interaction of different cell types with
      selectins. B cells infiltrating inflamed tissues like in Hashimoto's thyroiditis,
      also expressed these selectin-binding carbohydrates in parallel with the
      expression of E-selectin by surrounding follicular dendritic cells. Moreover, the
      crosslinking of these selectin-binding epitopes resulted in an increased binding
      of B cells to different integrin ligands. Thus, in addition to the involvement of
      integrins, E- and P-selectins could play an important role in the interaction of
      B lymphocytes with the endothelium during B cell extravasation into lymphoid
      tissues and inflammatory foci as well as in their organization into lymphoid
      organs.

PMID- 7523457
TI  - Moricizine concentration to guide arrhythmia treatment: with attention to elderly
      patients.
AB  - To test the relationship between plasma moricizine concentration and the
      electrocardiogram (ECG) and arrhythmia suppression, 17 symptomatic cardiac
      patients with 30 or more ventricular premature complexes per hour were studied.
      Seven patients were mature adults, less than 60 years of age; and ten were
      elderly adults, more than 60 years of age. During steady-state moricizine
      therapy, patients had plasma moricizine concentration determined over a dosing
      interval, and had standard 12-lead ECG and a 24-hour ambulatory ECG recorded. The
      mean moricizine dose was 215 +/- 29 mg every 8 hours; mean maximal moricizine
      concentration was 1.4 +/- 0.84 micrograms/ml; and mean t1/2 beta was 1.5 +/- 0.7
      hours. Baseline age-related differences were found, including prolonged
      electrocardiographic intervals (PR and QRS) (P < .05), increased ventricular
      arrhythmias (P < .05), and reduction in creatinine clearance (P < .05) in the
      elderly. Compared with pretreatment values, PR (P < .05) and QRS (P < .05)
      prolongation was observed, and was more marked in elderly patients. Over a dosing
      interval, there were dynamic changes on the ECG that paralleled plasma moricizine
      concentration; that is, peak and nadir intact moricizine concentration occurred
      simultaneously with ECG changes: QRS and JTc prolonged (P < .05), and PR
      prolongation approached significance (P = 0.09). Suppression of ventricular
      premature complexes of 80% or more occurred in 15 patients, and ventricular
      tachycardia was abolished in 10 of 12 patients. Probit analysis revealed that the
      therapeutic antiarrhythmic concentration ranged from 0.20 to 3.6
      micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523458
TI  - Contralateral thalamic projections predominantly reach transitional cortices in
      the rhesus monkey.
AB  - Connections between the thalamus and the cortex are generally regarded as
      ipsilateral, even though contralateral connections exist as well in several adult
      mammalian species. It is not known, however, whether contralateral
      thalamocortical projections reach particular cortices or whether they emanate
      from specific nuclei. In the rhesus monkey different types of cortices, ranging
      from transitional to eulaminate, vary in their cortical connectional pattern and
      may also differ in their thalamic connections. Because olfactory and transitional
      prefrontal cortices receive widespread projections, we investigated whether they
      are the target of projections from the contralateral thalamus as well. With the
      aid of retrograde tracers, we studied the thalamic projections of primary
      olfactory (olfactory tubercle and prepiriform cortex) and transitional orbital
      (areas PAII, Pro, 13) and medial (areas 25, 24, 32) areas, and of eulaminate
      (areas 11, 12, 9) cortices for comparison. To determine the prevalence of neurons
      in the contralateral thalamus, we compared them with the ipsilateral in each
      case. The pattern of ipsilateral thalamic projections differed somewhat among
      orbital, medial, and olfactory cortices. The mediodorsal nucleus was the
      predominant source of projections to orbital areas, midline nuclei included
      consistently about 25% of the thalamic neurons directed to medial transitional
      cortices, and primary olfactory areas were distinguished by receiving thalamic
      projections predominantly from neurons in midline and intralaminar nuclei.
      Notwithstanding some broad differences in the ipsilateral thalamofrontal
      projections, which appeared to depend on cortical location, the pattern of
      contralateral projections was consistent with cortical type rather than location.
      Labeled neurons in the contralateral thalamus were noted in midline, the
      magnocellular sector of the mediodorsal nucleus, the anterior medial and
      intralaminar nuclei, and ranged from 0 to 14% of the ipsilateral; they were
      directed primarily to olfactory and transitional orbital and medial cortices but
      rarely projected to eulaminate areas. Several thalamic nuclei projected from both
      sides to olfactory and transitional areas, but issued only ipsilateral
      projections to eulaminate areas. Though ipsilateral thalamocortical projections
      predominate in adult mammalian species, crossed projections are a common feature
      in development. The results suggest differences in the persistence of
      contralateral thalamocortical interactions between transitional and eulaminate
      cortices.

PMID- 7523456
TI  - Improvements to the competitive ELISA for detection of antibodies to Brucella
      abortus in cattle sera.
AB  - This paper reports improvements in the competitive ELISA (cELISA) for the
      detection of serum antibodies to Brucella abortus through modification of the
      coating of antigen and of the enzyme labelling of the monoclonal antibody
      conjugate. The covalent linkage of poly-L-lysine to the o-polysaccharide antigen
      of Brucella abortus enhanced its binding to the polystyrene matrix which resulted
      in a more efficient and reliable cELISA. Optimal discrimination between
      vaccinated and infected cattle was achieved by adjustment of the ratio between
      the monoclonal antibody used in the cELISA and the horseradish peroxidase. Both
      modifications resulted in a refined, more efficient and reliable cELISA with
      potential as a routine serodiagnostic assay for Brucellosis.

PMID- 7523459
TI  - Cerebellothalamocortical and pallidothalamocortical projections to the primary
      and supplementary motor cortical areas: a multiple tracing study in macaque
      monkeys.
AB  - The goal of the present study was to clarify whether the primary motor cortex
      (M1) and the supplementary motor cortex (SMA) both receive, via the motor
      thalamus, input from cerebellar and basal ganglia output nuclei. This is the
      first investigation that explores the problem by direct comparison, in the same
      animal, of thalamic zones that 1) project to M1 and SMA and 2) receive cerebellar
      nuclear (CN) and pallidal (GP) afferents. These four zones were mapped in two
      monkeys by means of two retrograde tracers for M1 and SMA injections and of two
      anterograde tracers for CN and GP injections. All injections were performed under
      electrophysiological control (microstimulation and multiunit recordings).
      Injections in cortical areas were restricted to the hand/arm representation; in
      the SMA, the tracer deposit was within the "SMA-proper" (or "area F3") and did
      not include its rostral extension ("pre-SMA" or "area F6"). It was found that
      zones of all four types formed a number of highly complex patches of labeling
      that were usually not confined to one cytoarchitectonically defined thalamic
      nucleus. The overlap of clusters of labeled terminals and perikarya was evaluated
      morphometrically (area measurements) on a number of coronal sections along the
      anteroposterior extent of the motor thalamus. In line with previous studies, the
      thalamic territories innervated by CN and GP afferents rarely overlapped.
      However, zones projecting to M1 and/or to SMA included thalamic regions receiving
      CN as well as GP projections, providing the first evidence of such overlap from
      individual animals. The present observations support the previous conclusion from
      this laboratory (based on transsynaptic labeling) that the SMA receives, apart
      from its strong pallidal transthalamic input, a CN transthalamic input. These
      present findings that both M1 and SMA are recipients of transthalamic inputs from
      GP and CN thus support the concept that a mixed subcortical input consisting of
      weighted contributions from cerebellum, basal ganglia, substantia nigra, and
      spinothalamic tract is directed to each functional component of the sensorimotor
      cortex.

PMID- 7523461
TI  - Course of spinocerebellar axons in the ventral and lateral funiculi of the spinal
      cord with projections to the anterior lobe: an experimental anatomical study in
      the cat with retrograde tracing techniques.
AB  - The fiber course of the spinocerebellar tracts in the ventral and lateral
      funiculi of the cat spinal cord were studied by a new approach, making
      cordotomies at different spinal levels or lesions of the restiform body followed
      by injections of HRP or WGA-HRP into the anterior cerebellar lobe. The
      retrogradely labeled axons showed characteristic distribution patterns related to
      the level and extent of the lesions. The results show the following. 1) The
      dorsal spinocerebellar tract (DSCT) originating ipsilaterally from the thoracic
      and upper lumbar segments ascends in the dorsolateral fasciculus. It undergoes a
      dorsal shift during its rostral course. The tract is topically arranged and
      passes through the restiform body. 2) The ventral spinocerebellar tract (VSCT)
      arising contralaterally from lower thoracic, lumbar, and more caudal segments
      passes via the ventral funiculus and ascends in the ventrolateral fasciculus.
      This tract is also topically arranged. It makes a lateral and then a dorsal shift
      during its ascending course. The main portion of the VSCT enters the cerebellum
      via the superior cerebellar peduncle. A minor portion originating from the
      sacrococcygeal region enters via the restiform body. 3) The spinocerebellar
      fibers originating ipsilaterally from the cervical enlargement ascend in the
      lateralmost part of the lateral funiculus in the area between the dorsolateral
      and ventrolateral fasciculi. These fibers form two groups, one passing through
      the restiform body, the other through the superior cerebellar peduncle. 4) The
      spinocerebellar fibers originating contralaterally from the central cervical
      nucleus pass through the ventral funiculus and ascend in the lateralmost part of
      the lateral funiculus, mainly in the ventrolateral fasciculus. Most of the fibers
      seem to pass through the superior cerebellar peduncle.

PMID- 7523462
TI  - Maturation of neuron types in nucleus of solitary tract associated with
      functional convergence during development of taste circuits.
AB  - Late fetal through postnatal development in sheep is a period of increasing
      convergence of afferent taste fibers onto second-order neurons in the nucleus of
      the solitary tract (NST). To learn whether neuron morphology alters in concert
      with convergence and neurophysiological development in NST, three-dimensional
      neuron reconstructions were made of cells in a functionally defined region of
      gustatory NST from Golgi preparations of the brainstem. Elongate, multipolar, and
      ovoid neurons were studied in fetuses from 85 days of gestation through the
      perinatal period (term = 147 days of gestation), to postnatal stages. Somal size
      and form, and dendritic complexity and extent, increased markedly from 85 to
      about 110 days of gestation in both of the proposed NST projection neurons,
      elongate and multipolar. From 130 days of gestation to postnatal ages, growth of
      dendrites of elongate neurons plateaued or declined, whereas dendrites of
      multipolar neurons apparently continued to increase in size and extent. In
      addition, spine density decreased on elongate neurons but remained stable on
      multipolar neurons. Morphological variables of ovoid cells, proposed interneurons
      in NST, did not alter over this later period. The data suggest that multipolar,
      not elongate or ovoid, neurons are logical candidates to receive the increasing
      afferent fiber input onto NST cells during late gestation. Also, neural activity
      from taste afferent fibers is more likely to have a role in altering NST neuron
      morphology at later, rather than earlier, developmental periods.

PMID- 7523465
TI  - Proceedings of the Second International Symposium on Cutaneous T-cell Lymphoma.
      Chicago, Illinois, Oct. 13-17, 1993.

PMID- 7523464
TI  - Treatment of cutaneous leishmaniasis.
AB  - The World Health Organization estimates that approximately 400,000 new cases of
      leishmaniasis occur worldwide each year. Cutaneous leishmaniasis is being
      encountered more frequently in the United States because of increasing travel and
      immigration from endemic areas. The indications for treatment and recommended
      treatment regimens reported in the infectious disease and dermatology literature
      vary widely. We examine both classic and newly developed therapeutic agents and
      modalities for cutaneous leishmaniasis. Proper therapy depends on species
      identification. New World leishmaniasis, in general, requires more aggressive
      therapy; parenteral antimonials are the drugs of choice. Physical modalities may
      suffice in most cases of Old World leishmaniasis because of its strong tendency
      toward spontaneous resolution.

PMID- 7523463
TI  - Innervation of laryngeal nerve paraganglia: an anterograde tracing and
      immunohistochemical study in the rat.
AB  - Carotid body-like organs, paraganglia, frequently occur in the superior and
      recurrent laryngeal nerves. The paraganglia are supplied with a rich innervation
      of unknown origin. In the present study, the origin of the innervation of the
      paraganglia of the rat was studied with two different techniques. One approach
      was anterograde tracing of wheat-germ agglutinin-horseradish peroxidase after
      injection into the nodose and jugular ganglia of the vagus and the superior
      cervical ganglion. The other approach was immunohistochemical staining for
      neuropeptides after excision of the superior cervical ganglion, or vagotomy.
      Antisera against neuropeptide Y, vasoactive intestinal polypeptide, and
      calcitonin gene-related peptide were utilized. Both the tracing method and
      calcitonin gene-related peptide immunohistochemistry after vagotomy showed that
      the paraganglia receive sensory innervation from the vagal ganglia. No labeling
      was detected in the paraganglia after injection of wheat-germ agglutinin
      horseradish peroxidase in the superior cervical ganglion. Excision of this
      ganglion did not lead to a decrease in the neuropeptide-Y innervation in the
      paraganglia, but most of this innervation in the surrounding blood vessels
      disappeared. The observations show that the superior cervical ganglion does not
      contribute to the innervation in the paraganglia and that the neuropeptide-Y
      innervation of the blood vessels originates from the superior cervical ganglion
      whereas that of the paraganglia has another origin, most likely local ganglionic
      cells. The results also suggest that the vasoactive intestinal polypeptide
      innervation in the paraganglia arises from local ganglionic cells. The two
      approaches complemented each other in mapping the afferent and efferent nerve
      supply of the paraganglia.

PMID- 7523467
TI  - Protein and fat metabolism in cows given somavubove before parturition.
AB  - Forty-one Holstein cows were injected with 0, 5, or 14 mg/d of bST for the last
      46 +/- 6 d before parturition. Compared with data for controls, the 5- and 14-mg
      doses of bST increased apparent protein synthesis about 16% before parturition.
      Exogenous bST before parturition increased apparent protein degradation 30%
      during wk 1 after parturition. During wk 1 of lactation, 14 mg of bST also
      increased milk protein yield 33%. No treatment differences were present in
      concentration of serum NEFA, body condition score, or thickness of subcutaneous
      fat. Therefore, administration of bST before parturition did not alter metabolism
      of subcutaneous fat. Prepartum treatment with 5 and 14 mg of bST increased and
      maintained serum somatotropin at 6.5 and 22.7 ng/ml, respectively, compared with
      1.6 ng/ml in controls. Concentrations of serum IGF-I were initially increased but
      were not maintained as parturition approached. On d -23, IGF binding protein 3
      was increased 65% but was not different among groups by d -7. For groups
      administered the 5 and 14 mg/d of bST, IGF binding protein 2 was decreased 40%.
      Administration of bST before parturition increased protein reserves and
      stimulated milk protein yield for 1 wk but did not alter metabolism of
      subcutaneous fat. Furthermore, energy balance appeared to be a major regulator of
      concentrations of IGF binding protein 3 and responsiveness of IGF-I to exogenous
      somatotropin before parturition.

PMID- 7523466
TI  - Cell adhesion molecule expression in capillaritis.

PMID- 7523460
TI  - Correlating gamma-aminobutyric acidergic circuits and sensory function in the
      electrosensory lateral line lobe of a gymnotiform fish.
AB  - Electric fish generate an electric field, which they sense with cutaneous
      electroreceptors. Electroreceptors project topographically onto the medullary
      electrosensory lateral line lobe (ELL). The ELL of gymnotiform electric fish is
      divided into four segments specialized to detect different aspects of the
      electrosensory input; it is also laminated with separate laminae devoted to
      electroreceptive input, interneurons, projection neurons, and feedback input. We
      have utilized antisera to glutamic acid decarboxylase (GAD) and gamma
      aminobutyric acid (GABA) to map the distribution of GABAergic cells and fibers in
      the ELL of the gymnotiform fish, Apteronotus leptorhynchus. Six types of
      GABAergic interneurons are found in ELL: Type 2 granular cells (granular layer)
      project to pyramidal cells; polymorphic cells (pyramidal cell layer) project to
      the non-GABAergic type 1 granular cells; ovoid cells (deep neuropil layer)
      project bilaterally upon basilar dendrites of pyramidal cells; multipolar cells
      (deep neuropil layer) project bilaterally, probably to dendrites and neurons
      within the deep neuropil layer; and neurons of the ventral molecular layer and
      stellate cells (molecular layer) project to apical dendrites of pyramidal cells.
      GABAergic bipolar cells in the nucleus praeminentialis, a rhombencephalic
      structure devoted to feedback in the electrosensory system, project in relatively
      diffuse fashion to pyramidal cells. We hypothesize that the various GABAergic
      circuits of the ELL can be correlated with specific functions: type 2 granular
      cells with adaptation, size of receptive field center, and gain; polymorphic
      cells and type 1 granular cells with regulation of surround inhibition; ovoid
      cells with common mode rejection; and neurons of the ventral molecular layer with
      adaptive gain control. The feedback GABAergic input from bipolar cells of n.
      praeminentialis to pyramidal cells may be part of a searchlight mechanism similar
      to the one postulated for thalamocortical systems.

PMID- 7523468
TI  - Emergence in human dental plaque and host distribution of amylase-binding
      streptococci.
AB  - Salivary amylase is known to bind specifically to several species of oral
      streptococci. To assess the importance of this interaction in bacterial
      colonization of the oral cavity, we determined the proportion and identity of
      amylase-binding bacteria (ABB) in dental plaque of humans and various salivary
      amylase-secreting and non-secreting mammalian species. The numbers of ABB in
      undisturbed plaque collected over time from tooth surfaces of six human
      volunteers or from 14 other mammalian species were determined by means of a
      replicating assay. The mean proportion of ABB cultured aerobically from human
      teeth at 2 h was 10.5% (SD 10), at 8 h 7.9% (8), at 24 h 13% (11), and at 48 h
      12% (9). The mean proportion of anaerobically cultured ABB found at 2 h was 3%
      (SD 4), at 8 h 5% (5), at 24 h 12% (9), and at 48 h 16% (12). Amylase-binding
      bacteria cultured from these samples resembled Streptococcus mitis, Streptococcus
      gordonii, Streptococcus salivarius, Streptococcus crista, or unidentified
      streptococci. In addition, only animals exhibiting salivary amylase activity in
      their saliva harbored ABB (ranging from 2 to 31% of the total flora), with the
      exception of the pig, where no ABB were found to colonize, despite considerable
      amylase activity in saliva. Only strains resembling S. mitis and S. salivarius
      and unspeciated strains were isolated from these mammals. These results suggest
      that amylase-binding streptococci are the predominant ABB in human plaque, and
      their numbers generally increase as plaque develops. Since ABB colonized only the
      oral cavities of hosts demonstrating salivary amylase activity, the ability to
      bind amylase may play an important role in oral colonization by these bacteria.

PMID- 7523470
TI  - Immunohistochemical margin control applied to Mohs micrographic surgical excision
      of dermatofibrosarcoma protuberans.
AB  - BACKGROUND: Surgical treatment of dermatofibrosarcoma protuberans has a high rate
      of recurrence presumably secondary to persistent residual tumor. Recently an
      antigenic marker, CD34, has demonstrated specificity for this tumor. OBJECTIVE:
      To improve the microscopic detection of dermatofibrosarcoma protuberans tumor
      elements in Mohs micrographic surgical sections by incorporating immunohistologic
      staining. METHODS: Standard Mohs micrographic surgical technique was used,
      coupled with standard immunohistochemical procedures using an antibody to the
      CD34 antigen. RESULTS: Immunohistochemical staining with anti-CD34 of Mohs
      micrographic sections clearly delineated the extent of the tumor elements.
      CONCLUSIONS: We anticipate that the application of this immunohistochemical
      modified Mohs surgical technique will further enhance the detection of insidious
      portions of tumor thereby enhancing removal and reducing recurrence.

PMID- 7523471
TI  - Metaphor in illness and nursing: a two-edged sword. A discussion of the social
      use of metaphor in everyday language, and implications of nursing and nursing
      education.
AB  - Study of the use of language, and in particular metaphor, is a valuable approach
      to an understanding of the experiential, lived world of the patient. There is an
      emerging focus on the need for nursing care to be informed by an appreciation of
      the experience of the phenomena of illness and patienthood. Related nursing
      epistemological issues are discussed as background. The anatomy and social use of
      metaphor in language in general are described. The metaphors surrounding cancer
      are examined to illustrate the two main functions of metaphor; the instrumental
      and the expressive. Illness metaphors may have negative consequences, imbibing
      myth, fear and stigma. However, the author concludes that awareness of the
      expressive function of metaphor provides a valuable focus for listening to and
      understanding the experience of the patient. Finally, some of the implications of
      both functions of metaphor in nurse education are outlined.

PMID- 7523469
TI  - Affinity and specificity of the interactions between Streptococcus mutans antigen
      I/II and salivary components.
AB  - Adherence to salivary pellicle-coated tooth surfaces and aggregation by salivary
      components of Streptococcus mutans involves a major cell surface protein termed
      antigen (Ag) I/II. The objectives of this study were to evaluate the affinity and
      specificity of the interactions between AgI/II and human saliva in assays of 125I
      AgI/II binding to saliva-coated hydroxyapatite (SHA) and of S. mutans aggregation
      by salivary agglutinin (SAG), monitored turbidimetrically. 125I-AgI/II binding to
      SHA followed saturation kinetics, and Scatchard plot analysis indicated two
      binding sites with dissociation constants of the order of 10(-10) mol/L and 10(
      9) mol/L. The binding to SHA of the C-terminal one-third of AgI/II which
      corresponds to AgII was less than one-fifth that of the whole molecule and did
      not show evidence of saturation. The binding of 125I-AgI/II was inhibited by
      native or recombinant fragments that mapped in the N-terminal part of the
      molecule and that contained the alanine-rich repeat region, whereas fragments
      mapping at the central or C-terminal one-third had no effect. As with binding to
      SHA, the regions of AgI/II which inhibited aggregation mapped at the N-terminal
      part of the molecule, but, in addition, a recombinant segment mapping at the
      central part and containing the proline-rich repeat region was also inhibitory.
      The S. mutans-aggregating activity of SAG or whole saliva was inhibited by amino
      compounds, and most strongly by L-lysine and analogues possessing omega-primary
      amine groups. These data support the role of AgI/II as an adhesin with high
      affinity binding for SHA receptors, mediated by the N-terminal part of the
      molecule. This region is also involved in SAG-induced S. mutans aggregation,
      which is sensitive to amino compounds.

PMID- 7523472
TI  - 26th Bethesda conference: recommendations for determining eligibility for
      competition in athletes with cardiovascular abnormalities. Task Force 6:
      arrhythmias.

PMID- 7523473
TI  - Balancing the circulation: theoretic optimization of pulmonary/systemic flow
      ratio in hypoplastic left heart syndrome.
AB  - OBJECTIVES: This study examined the effects of the pulmonary (QP)/systemic (QS)
      blood flow ratio (QP/QS) on systemic oxygen availability in neonates with
      hypoplastic left heart syndrome. BACKGROUND: The management of neonates with
      hypoplastic left heart syndrome is complex and controversial. Both before and
      after surgical palliation and before heart transplantation, a univentricle with
      parallel pulmonary and systemic circulations exists. It is generally assumed that
      balancing pulmonary and systemic blood flow is best to stabilize the circulation.
      METHODS: We developed a mathematical model that was based on the simple flow of
      oxygen uptake in the lungs and whole-body oxygen consumption to study the effect
      of varying the QP/QS ratio. An equation was derived that related the key
      variables of cardiac output, pulmonary venous oxygen saturation and the QP/QS
      ratio to systemic oxygen availability. RESULTS: The key findings are 1) as the
      QP/QS ratio increases, systemic oxygen availability increases initially, reaches
      a maximum and then decreases; 2) for maximal systemic oxygen availability, the
      optimal QP/QS ratio is < or = 1; 3) the optimal QP/QS ratio decreases as cardiac
      output or percent pulmonary venous oxygen saturation, or both, increase; 4) the
      critical range of QP/QS, where oxygen supply exceeds basal oxygen consumption,
      decreases as cardiac output and percent pulmonary venous oxygen saturation
      decrease; 5) the relation between oxygen availability and QP/QS is very steep
      when QP/QS approaches this critical value; and 6) the percent oxygen saturation
      of systemic venous blood is very low outside the critical range of QP/QS and high
      within the critical range. CONCLUSIONS: This analysis provides a theoretic basis
      for balancing both the pulmonary and systemic circulation and suggests that
      evaluating both systemic arterial and venous oxygen saturation may be a useful
      way to determine the relative pulmonary and systemic flows. When high systemic
      arterial and low systemic venous oxygen saturation are present, pulmonary blood
      flow should be decreased; conversely, when both low systemic arterial and venous
      oxygen saturation are present, more flow should be directed to the pulmonary
      circulation.

PMID- 7523474
TI  - The use of cutaneous microdialysis to measure substance P-induced histamine
      release in intact human skin in vivo.
AB  - BACKGROUND: The purpose of this study was to introduce a microdialysis technique,
      which makes it possible to measure the release of small inflammatory mediators
      into the extracellular water space in intact human skin in vivo. Using this
      technique, we have studied the histamine releasing properties of substance P, a
      putative skin mast cell releasing agent. METHODS: Small hollow fibers were
      inserted into the upper dermis of nine healthy subjects. Each fiber was perfused
      with Kreb's Ringer bicarbonate buffer at a rate of 3.0 microliters/min. After
      establishment of a baseline, each fiber was challenged intracutaneously with
      substance P (0 to 4 mumol/L). Samples were collected at 2-minute intervals for 18
      minutes. Histamine was measured by a fluorometric method, which correlated with
      an enzyme immunoassay (r = 0.96). RESULTS: Baseline dialysate histamine
      concentration was 1.7 +/- 0.3 ng/ml. Peak histamine release after injection of
      vehicle, 0.5, 1, 2, and 4 mumol/L substance P was 0.0, 1.0, 6.0, 44.5, and 88.5
      ng/ml, respectively (p = 0.00002). Statistically significant histamine release
      was demonstrated with 1.0 mumol/L substance P and greater. Most peak values were
      seen 2 to 4 minutes after injection. The histamine elimination showed a
      monoexponential decline; dialysate histamine half-life was 3.81 +/- 0.28 minutes.
      CONCLUSIONS: This study showed that substance P releases histamine in a dose
      dependent manner from intact human skin in normal subjects. We suggest that
      microdialysis may be a promising technique for the evaluation of mediator levels
      in intact human skin after intradermal injection of an inflammatory or allergenic
      stimulus.

PMID- 7523476
TI  - Nutrition services for children with developmental disabilities and chronic
      illnesses in education programs.
AB  - OBJECTIVE: To determine the number of children attending school who require
      special nutrition services, types of nutrition services provided to children,
      involvement of registered dietitians in provision of nutrition services in the
      school setting, and continuing education needs of school nutrition personnel.
      DESIGN/SAMPLE: Pretested questionnaires were mailed to a national, systematic
      random sample of 600 school nutrition managers, 600 district school nutrition
      directors/supervisors, and 600 district special education program directors.
      Response rates were 32.7%, 46.2%, and 32.8%, respectively. STATISTICAL ANALYSES
      PERFORMED: Descriptive statistics were used to summarize data, including means,
      standard deviations, frequencies, and percentages. RESULTS: A large percentage of
      school nutrition managers (46%) reported that they served no children with
      special food and nutrition needs. Special food and nutrition needs most
      frequently encountered by all groups included food allergy, food intolerance,
      diabetes, and conditions with which feeding problems are associated. The skills
      of dietitians were used by 23% of school nutrition managers, 21% of district
      school nutrition directors/supervisors, and 15% of special education program
      directors. Continuing education needs were greatest for the areas of assessing
      liability, calculating macronutrient content of menus, modifying menus, and
      understanding the physical and emotional needs of children with special needs.
      APPLICATIONS/CONCLUSIONS: Communication between nutrition service providers and
      special education providers needs to be strengthened. A need exists to include
      nutrition in Individualized Education Programs for children in special education.
      Many opportunities are available for registered dietitians to provide consulting
      services for school nutrition programs related to special needs.

PMID- 7523475
TI  - Role of protein tyrosine kinases in CD40/interleukin-4-mediated isotype switching
      to IgE.
AB  - The B-cell antigen CD40 transduces signals, which synergize with interleukin (IL)
      4 to induce IgE synthesis in human B cells. IL-4 induces epsilon germline
      transcription but not mature epsilon transcripts or IgE protein synthesis in B
      cells. Addition of anti-CD40 monoclonal antibody to IL-4-treated B cells results
      in deletional S mu--> S epsilon switch recombination, expression of mature
      epsilon transcripts, and IgE synthesis and secretion. Because both IL-4 and anti
      CD40 induce protein tyrosine phosphorylation in B cells, we investigated the role
      of protein tyrosine kinase in IL-4/CD40-mediated IgE synthesis. The protein
      tyrosine kinase inhibitors genistein and herbimycin A, but not the protein kinase
      C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) or the protein
      kinase A inhibitor N-2-guanidinoethyl-5-isoquinolinesulfonamide, inhibited IgE
      synthesis in B cells stimulated with IL-4 and CD40. Genestein and herbimycin, but
      not H7, inhibited IL-4-driven epsilon germline transcription in B cells. Both
      genestein and herbimycin, but not H7, inhibited CD40-mediated IgE synthesis in B
      cells pretreated for 4 days with IL-4 to allow optimal expression of epsilon
      germline transcripts. Inhibition of IgE synthesis in these cultures was
      accompanied by inhibition of S mu--> S epsilon deletional switch recombination as
      assayed by nested polymerase chain reactions. These results suggest that
      activation of protein tyrosine kinase plays an important role in both the IL-4
      and the CD40 signalling pathways that lead to IgE isotype switching in B cells.

PMID- 7523477
TI  - Tyrosine hydroxylase indicates cell differentiation of catecholamine biosynthesis
      in neuroendocrine tumors.
AB  - The intracellular localization of tyrosine hydroxylase (TH), which is the rate
      limiting enzyme in catecholamine (CA) biosynthesis, and its activity in various
      adrenal and other neuroendocrine tumors was studied. TH was strongly localized in
      adrenal medulla, pheochromocytoma, and paraganglioma, but was scatteredly
      expressed in neuroblastoma. TH was not detected in adrenocortical tumors,
      ganglioneuroma, and other neuroendocrine tumors. Neuron specific enolase (NSE)
      was found in all neuroendocrine tumors, but Grimelius staining showed only the
      secreting granules of the tumor cells. TH activity was significantly high in
      pheochromocytoma and paraganglioma as compared with that in normal adrenal gland,
      whereas TH activity was low in a neuroblastoma and was undetectable in other
      tumors. These findings indicate that TH correlates well with the biosynthetic
      function of CA in the tumor cell and, thus, both the immunostaining of TH and the
      measurement of its activity in adreno-medullary and related tumors may provide
      some information about the process of cell differentiation in these tumors.

PMID- 7523478
TI  - Glycoprotein hormone isomorphism and assay discrepancy: the paradigm of
      luteinizing hormone (LH).

PMID- 7523479
TI  - European collaborative study of luteinizing hormone assay: 1. Epitope specificity
      of luteinizing hormone monoclonal antibodies and surface mapping of pituitary and
      urinary luteinizing hormone.
AB  - This report describes the results of the first part of the collaborative study
      organized by a working group sponsored by the Community Bureau of Reference of
      the European Community Commission. The whole study was designed to understand the
      causes of discrepancy among LH immunoassay methods. In the parent work, we
      studied the characteristics of 55 monoclonal antibodies to LH which allowed us to
      establish a detailed map of the antigenic surface of the hormone. In the present
      report we used this information to interpret the discrepancy in LH concentrations
      assayed with 12 different methods in 300 sera from subjects with various clinical
      conditions. The 55 monoclonal antibodies provided by 11 commercial companies were
      tested in various experiments: the apparent affinity of the antibodies was,
      generally but not always, higher for LH presented by a second antibody coated to
      plastic than for LH directly coated to plastic; 26% of the antibodies recognized
      the alpha subunit, 26% the beta subunit and 48% reacted only with the
      holomolecule (anti-alpha beta); only 28% of the antibodies were strictly specific
      for LH. Criss-cross experiments allowed us to distinguish 13 antigenic regions on
      the surface of LH: 6 were located on the alpha subunit, 3 on the beta subunit and
      4 on the holomolecule. The monoclonal antibodies to the alpha beta regions
      further separated into 12 clusters of reactivity. Accordingly, LH appeared to
      exhibit at least 21 epitopes. Comparison of the immunoreactivity of various LH
      preparations indicated that highly purified pituitary LH and immunoaffinity
      purified urinary LH reacted similarly with the monoclonal antibodies and strongly
      differed from crude urinary LH. These data indicated that the immunoreactivity of
      an LH preparation depends mainly upon the degree of purification and not that
      much upon the origin of the preparation. The epitope specificity of the
      monoclonal antibodies used in 11 commercially available LH assay kits was also
      determined: 10 kits used at least one anti-alpha beta monoclonal antibody
      associated with an anti-beta monoclonal antibody in 7 cases or another anti-alpha
      beta monoclonal antibody in 3 cases; one kit used an anti-alpha monoclonal
      antibody associated with an anti-beta monoclonal antibody. None of the kits were
      strictly identical with regards to the epitope specificity of the monoclonal
      antibodies used.

PMID- 7523480
TI  - European collaborative study on luteinizing hormone assay: 2. Discrepancy among
      assay kits is related to variation both in standard curve calibration and epitope
      specificity of kit monoclonal antibodies.
AB  - This report describes the results of the second part of the collaborative study
      organized by a working group sponsored by the Community Bureau of Reference of
      the European Community Commission. The whole study was designed to understand the
      causes of discrepancy among LH immunoassay methods. In the parent report we
      described the characteristics of LH monoclonal antibodies. In the present work we
      focused on the comparison of 11 commercially available monoclonal antibody based
      kits and one polyclonal antibody based RIA. Recovery experiments of the second IS
      80/552 and of a related LH preparation showed that curve calibration differed
      among kits. The ratio between the LH recovery of the two most different kits was
      2.30. LH concentrations were determined, using the 12 assay methods in the sera
      of prepubertal children (n = 46), normal women (n = 26) and men (n = 39) before
      and after LHRH stimulation, post-menopausal women (n = 29) and patients with
      renal failure (n = 71) or polycystic ovaries (n = 28). In children LH was
      detected in 0 to 80% of the sera depending on the kit. In adults, the mean LH
      concentration provided by the 12 kits varied from 6.0 to 13.55 IU/L showing a
      ratio of 2.26 between the two most different kits. A thorough statistical
      analysis allowed to distinguish two groups of kits. The first groups consisting
      of 6 kits provided results close to those obtained by the RIA. The 5 other kits
      misrecognized circulating LH in subjects with various clinical status. These 5
      kits were the only ones to use, as labelled probes, monoclonal antibodies
      specific for the holohormone (anti-alpha beta) whereas the 6 other kits used, as
      labelled probes, monoclonal antibodies directed to the alpha (1 kit) or the beta
      subunit (5 kits). In both groups, the coated monoclonal antibodies are directed
      to either the beta-subunit (1/6 and 2/5 kits) or the holohormone (5/6 and 3/5
      kits). Taken together these data suggest that discrepancy among LH assay kits is
      related to variation in standard curve calibration and in epitope specificity of
      monoclonal antibodies used in the kits. These findings may prove to be
      instrumental to alleviate differences among LH assay methods.

PMID- 7523484
TI  - Prevalence of antibodies to hepatitis C virus in Greek patients with chronic
      liver disease.

PMID- 7523481
TI  - TSH receptor gene expression in retroocular fibroblasts.
AB  - RNA was isolated from fibroblasts from the retroocular area, from endomysial
      fibroblasts obtained from orbital lateral rectus muscle, and from abdominal skin
      fibroblasts. The RNA was reverse transcribed into cDNA which was then used as a
      template for PCR with primers encompassing a portion (nucleotides 989-1235) of
      the extra-cellular domain of the human TSH receptor (hTSH-R). A definite 247 BP
      product was detected from fibroblast RNA by ethidium bromide staining, and was
      confirmed by hybridization with labelled hTSH-R cDNA. The product had homology
      with the known TSH-R cDNA. These studies indicate that human fibroblasts can
      express hTSH-R, and they suggest that a cross reactive immunologic response
      between anti-hTSH-R and these fibroblast TSH receptors may play a role in the
      genesis of Graves' ophthalmopathy.

PMID- 7523482
TI  - Cocaine babies: a result of multiple teratogenic influences.
AB  - The history of cocaine use is reviewed. Cocaine teratogenesis has only recently
      been studied, and initial human studies had serious methodological flaws. These
      flaws included ascertainment bias, publication bias (studies finding cocaine
      effects have been more likely to be presented or published), and overemphasis on
      the perinatal period. Comparison with alcohol teratogenesis shows that alcohol is
      a more potent teratogen, which, however, produces major and specific effects
      (fetal alcohol syndrome) in less than 10% of offspring with heavy alcohol
      exposure during pregnancy. Nonspecific minor congenital anomalies or fetal
      alcohol effects are seen in a larger number. Personal experience with two groups
      of children exposed to cocaine in utero is reviewed. Insurance patients gained
      weight, took vitamins, and generally, their children did well in spite of cocaine
      use. Indigent patients were usually unmarried and often "street people," probably
      used more cocaine, generally used other drugs as well, often did not gain weight
      during pregnancy, and were much more likely to have children with problems.
      Surveys show that most cocaine users also use alcohol, often simultaneously.
      Those who use both agents are more likely to have troubled backgrounds and
      antisocial behavior and to drop out of treatment programs than those who use only
      alcohol. Cocaethylene or ethylbenzoylecgonine is formed in the liver when cocaine
      and alcohol are simultaneously ingested. It is a potent stimulant and dopamine
      uptake blocker that is more toxic to myocardial cells than is cocaine. Good
      nutrition is now known to be very important in preventing congenital anomalies
      and fetal death. A multihit model of neurologic handicap, which stresses the
      importance of a good postnatal environment, is briefly outlined.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7523483
TI  - Transmission of hepatitis C virus by organ transplantation in the United Kingdom.
AB  - This study employed a second-generation anti-HCV ELISA, and a second-generation
      recombinant immunoblot assay and hepatitis C virus RNA detection by polymerase
      chain reaction to investigate the anti-HCV prevalence in 554 British organ donors
      and the transmission of hepatitis C virus to heart, liver and kidney recipients
      between 1984 and 1991. Serum samples from six (1.08%) donors were reactive in the
      second-generation anti-HCV ELISA and four (67%) of these gave positive or
      indeterminate results in the recombinant immunoblot assay-2. Of the 15 recipients
      of these organs from hepatitis C virus-confirmed positive/indeterminate donors,
      14 (93%) acquired hepatitis C virus infection and seven (47%) had evidence of
      hepatitis C virus-related liver disease after transplantation and no evidence of
      blood transfusion-related transmission. Only six of the 15 (40%) recipients had
      detectable anti-HCV after transplantation, while 12 of 14 (86%) patients tested
      had hepatitis C virus RNA in their serum detectable by "nested" polymerase chain
      reaction. These data indicate a very high rate of transmission with a major risk
      of the development of liver disease. We believe our study supports the testing of
      all British organ donors for anti-HCV and that organs from anti-HCV-positive
      patients should not be transplanted unless the recipient has life-threatening
      disease and there is a donor shortage, when their use may be justified. Since
      there are time constraints on organ donor testing, which may frequently be done
      on call during unsocial hours, we would recommend second-generation ELISA as the
      current screening test of choice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523485
TI  - Anti-GOR antibodies in anti-hepatitis C virus positive subjects with and without
      virus replication and liver disease.

PMID- 7523486
TI  - Fixation conditions affect the intensity but not the pattern of NADPH-diaphorase
      staining as a marker for neuronal nitric oxide synthase in rat olfactory bulb.
AB  - NADPH-diaphorase (NADPH-d) is commonly used as a histochemical marker for the
      neuronal form of the enzyme nitric oxide synthase (NOS). A recent biochemical
      study showed that in broken-cell preparations NADPH-d activity did not fully
      represent NOS and that NOS-unrelated NADPH-d activity was suppressed during
      fixation. Because it is unknown whether fixation also affects NOS-associated
      NADPH-d activity, we investigated the effects of various widely used fixatives on
      NADPH-d staining in relation to NOS immunoreactivity, obtained with polyclonal
      antibodies, in rat olfactory bulb. We found that the intensity of NADPH-d
      staining associated with NOS, as well as that unrelated to NOS, depends on
      fixation conditions. Addition of glutaraldehyde or lysine/sodium periodate to the
      fixative decreased intensity of NADPH-d staining. Fixative-dependence of NADPH-d
      staining was observed not only in the presence of the "normal" co-substrate beta
      NADPH but also in the presence of the stereoisomer alpha-NADPH. Unlike the
      staining intensity, the staining pattern of NOS-associated as well as NOS
      unrelated NADPH-d did not change after treatment with various fixatives. Our
      findings are of considerable practical significance because it has become clear
      that fixation conditions affect the sensitivity but not the selectively of the
      NADPH-d reaction as a marker for the presence of NOS.

PMID- 7523487
TI  - Nitric oxide synthase and NADP-linked glucose-6-phosphate dehydrogenase are co
      localized in brush cells of rat stomach and pancreas.
AB  - The epithelia of the respiratory and gastrointestinal tract and their appendages
      contain a distinct population of disseminated epithelial cells called brush cells
      or caveolated cells. On the basis of their structure, it was suggested that brush
      cells might serve as chemo- or volume receptors that play a role in certain
      aspects of gastrointestinal and bronchopulmonary secretion or motility. In the
      present study we provide first clues to a possible function of this widespread
      epithelial cell type. Brush cells of the rat gastric cardia and major pancreatic
      duct display strong immunoreactivity for nitric oxide synthase (NOS) and also
      exhibit high activity of NADPH-diaphorase. This NADPH-oxidizing activity was
      previously shown to be mediated by a specific domain of the sequence of the NOS.
      NADPH, in turn, appears to be delivered by glucose-6-phosphate dehydrogenase,
      which we found in brush cells at particularly high levels. We conclude that brush
      cells of the stomach and pancreas may represent a specialized population of
      paracrine cells that use nitric oxide as a messenger molecule to control certain
      gastrointestinal functions.

PMID- 7523490
TI  - Detection of DNA adducts in basal and non-basal cells of the hamster trachea
      exposed to benzo(a)pyrene in organ culture.
AB  - DNA adducts were quantified in hamster tracheas exposed to benzo(a)pyrene (BP) in
      organ culture, in basal as well as in non-basal cells, by in situ detection with
      an adduct-specific rabbit antiserum (W2/01) and with a mouse monoclonal antibody
      against human cytokeratins 5 and 8 (RCK102) to identify hamster trachea basal
      cells. Recognition by W2/01 of the adduct of (+)-anti-7,8-dihydroxy-9,10-epoxide
      of BP (BP-diolepoxide; BPDE) to deoxyguanosine (dG) was checked on human white
      blood cells (WBCs) exposed to BP together with 3-methylcholanthrene (3MC)-induced
      rat-liver microsomes. By comparison with the adduct levels determined by 32P post
      labeling, a lower detection limit of about 1 adduct per 10(6) nucleotides could
      be deduced. Next, tracheal rings were exposed to BP (40 microM) in organ culture
      for 2 days, then washed and cultured without BP for another 3 days. At different
      time points epithelial cells were isolated and cytospin preparations made.
      Staining of BP DNA adducts combined with that of cytokeratin (both visualized
      with fluorescence) allowed detection of adducts in both basal and non-basal cells
      in the same preparation. BP DNA adduct formation in basal and non-basal cells
      after 2 days of exposure to BP was not different. However, on removal of BP the
      adducts disappeared significantly faster from basal cells than from non-basal
      cells. The combination of the two antibodies mentioned above thus allows
      selective determination of BP DNA adduct levels in different cell types. This
      could be of importance with regard to the involvement of specific cell types in
      the process of tumor initiation.

PMID- 7523488
TI  - In situ hybridization and cytochemistry: localization of mRNA at stained
      neuromuscular junctions with 33P-labeled probes.
AB  - We modified the Karnovsky and Roots method of staining sites of
      acetylcholinesterase (AChE) activity at neuromuscular junctions (NMJs) to survive
      the lengthy, multiple steps of in situ hybridization and autoradiography. When
      the original method of Karnovsky and Roots is used to identify the muscle
      endplates, the stain does not survive the in situ hybridization procedures and
      association of mRNA to specific endplates can be inferred only indirectly. The
      successful modification involves secondary staining with diaminobenzidine (DAB)
      and H2O2 using the Karnovsky-Roots staining reaction product as a catalyst.
      Mounted longitudinal cryosections of mouse sternocleidomastoid muscle were fixed
      and stained in one step on the slide with paraformaldehyde plus the Karnovsky
      Roots stain, followed by DAB-H2O2 secondary staining. The tissues were then
      processed for in situ hybridization and probed for the acetylcholine receptor
      (AChR) epsilon-subunit mRNA, known to be localized at the NMJ. The probe was
      labeled with 33P, which is ideal for in situ hybridization. By this procedure,
      the endplate stain was retained even after the hybridization and autoradiographic
      procedures, and the developed grains due to radiolabeling of the AChR epsilon
      subunit mRNA were localized at readily identified endplates.

PMID- 7523491
TI  - Distribution of hyaluronan in bull reproductive organs.
AB  - To study the expression of hyaluronan in male reproductive organs and the origin
      of seminal plasma hyaluronan, we stained various parts of the bull reproductive
      tract for hyaluronan using a biotinylated probe derived from cartilage
      proteoglycan (bHABC). The potential loss of hyaluronan during tissue processing
      was checked with a novel technique by blotting frozen tissue sections on
      nitrocellulose and staining the blots with bHABC. In the same tissues the CD44
      receptor was visualized by Hermes 1 antibody. The testes showed only traces of
      hyaluronan, whereas both the epithelium and the connective tissue of seminal
      vesicle, prostate, Cowper's gland, and epididymis were positive in bHABC
      staining. Hyaluronan was localized on the basolateral surfaces of these
      epithelial cells. The secretions inside the seminal vesicle and in the ducts of
      prostate and Cowper's gland were HA-positive, whereas the luminal contents of
      seminiferous tubules and epididymis were unstained both in paraffin sections and
      in the in situ blocks. The data indicate that hyaluronan in seminal plasma
      originates from the accessory sex glands. The co-localization of CD44 with
      hyaluronan in the basolateral surfaces of the accessory gland epithelia and its
      absence from other epithelia with little or no hyaluronan supports its role as a
      hyaluronan receptor.

PMID- 7523492
TI  - T cell-independent and T cell-dependent B cell activation increases IFN-gamma R
      expression and renders B cells sensitive to IFN-gamma-mediated inhibition.
AB  - We have studied the relationship between B cell activation and the ability of IFN
      gamma to inhibit B cell differentiation. The LPS activation of conventional and
      CD5+ B cells resulted in increased IFN-gamma R expression and increased the
      ability of IFN-gamma to inhibit LPS-induced B cell differentiation correlated
      with increased IFN-gamma R expression. We detected increased B cell IFN-gamma R
      expression 12 h after activation, and maximal IFN-gamma R expression was observed
      at 24 h. Activation of B cells by F(ab2)' anti-IgM induced a similar increase in
      IFN-gamma R expression. In autoimmune New Zealand Black mice, both conventional
      and CD5+ B cells showed a pattern of IFN-gamma R expression similar to that seen
      in DBA/2 mice, and both populations of B cells were sensitive to inhibition by
      IFN-gamma. To examine the role of IFN-gamma in the regulation of T cell-dependent
      B cell responses, we activated B cells with the CDC35 T cell line (which is
      specific for rabbit IgG). When rabbit anti-mouse Ig-treated B cells were
      activated by CDC35 T cells, we found that B cells exhibited increased IFN-gamma R
      expression by 48 h; we also found that IFN-gamma inhibited CDC35-mediated IgM
      secretion to a degree similar to IFN-gamma inhibition of T cell-independent B
      cell differentiation. Additionally, IFN-gamma inhibited CDC35-stimulated B cells
      even in the presence of exogenous IL-4 and IL-5. This study establishes the
      importance of IFN-gamma as a regulator of both T cell-independent and T cell
      dependent B cell differentiation.

PMID- 7523489
TI  - Expression of c-kit and kit ligand proteins in normal human tissues.
AB  - The c-kit receptor and its cognate ligand, KL, play a critical role in
      melanogenesis, gametogenesis, and hematopoiesis. Studies on the expression of c
      kit and KL have been primarily focused on mouse development. We undertook the
      present study to characterize the pattern of expression of these molecules in
      normal adult human tissues. Using immunohistochemistry and consecutive tissue
      sections from the same block, we evaluated a variety of well-preserved normal
      tissues for c-kit and KL microanatomic distribution. c-kit protein was identified
      in tissue mast cells, melanocytes, glandular epithelial cells of breast, parotid,
      dermal sweat, and esophageal glands. Scattered c-kit immunoreactivity was also
      observed for testicular and ovarian interstitial cells. A striking regional
      distribution of c-kit was detected in the central nervous system, particularly in
      the cerebellum, hippocampus, and dorsal horn of the spinal cord. KL protein was
      identified in cells complementary to staining for the receptor, such as glandular
      myoepithelium of breast and sweat glands. Intense KL immunoreactivity was
      observed in smooth muscle cells of the bladder, cervix, uterus, and
      gastrointestinal tract, as well as in striated and cardiac muscle. Strong KL
      staining was also detected in prostate fibromuscular stroma cells. In the central
      nervous system, KL expression was confined to Golgi and Purkinje cells in the
      cerebellum. These results suggest a role for this receptor and its ligand in the
      maintenance of a variety of fully differentiated tissues.

PMID- 7523493
TI  - Characterization of the activation-associated isoform of CD43 on murine T
      lymphocytes.
AB  - A rat mAb termed 1B11 recognizes a 130-kDa cell surface glycoprotein expressed on
      T lymphocytes. Transfection studies using the Cd43 gene transfected into murine L
      cells, and immunoblots using anti-peptide Abs specific for the CD43 polypeptide
      identified the 1B11 Ag as the 130-kDa isoform of murine CD43. mAb 1B11 fails to
      recognize the other major CD43 isoform, 115-kDa CD43, either by Western blotting
      or by FACS analysis, thus differing from the previously characterized anti-CD43
      mAb S7 that recognizes only the CD43 115-kDa isoform and not the CD43 130-kDa
      isoform. CD43 130-kDa recognized by mAb 1B11 is differentially expressed on T
      lymphocytes. Whereas most CD4-8-, CD4+8+, and CD4-8+ thymocytes express 130-kDa
      CD43 constitutively, the Ag is expressed by less than 20% of CD4+ T cells in
      immature and mature populations. On activation, expression of 130-kDa CD43 is up
      regulated dramatically on CD4+ T lymphocytes, and to a lesser extent on CD8+ T
      lymphocytes. In contrast, T cell activation resulted in only minor up-regulation
      of 115-kDa CD43. CD43 130-kDa contains sialylated O-linked carbohydrate; however,
      recognition by mAb 1B11 is not dependent on the presence of sialic acid.
      Interestingly, removal of sialic acid by neuraminidase treatment of 1B11-negative
      CD4+ T lymphocytes or 1B11-negative EL4 cells confers 1B11 reactivity, suggesting
      that the 1B11 epitope is masked by sialic acid residues on the CD43 115-kDa
      isoform. The isoelectric point (pl) of 130-kDa CD43 was determined to be 6.0,
      which is higher than the pl reported for 115-kDa CD43. Different molecular
      properties of 115-kDa and 130-kDa CD43 and their differential expression in T
      cell subsets may indicate specific roles for these CD43 isoforms in T cell
      ontogeny and/or T cell function.

PMID- 7523494
TI  - Characterization of soluble CD44 in the circulation of mice. Levels are affected
      by immune activity and tumor growth.
AB  - ELISA determinations revealed substantial concentrations (0.49 to 2.10
      micrograms/ml) of soluble CD44 in murine serum, with some variation among normal
      mouse strains. At least three species of CD44 were identified by
      immunoprecipitation and SDS-PAGE analysis of serum. The most prominent was
      indistinguishable in mobility from that extracted from normal and transformed
      lymphocytes and was estimated in this way to be approximately 90 kDa. A similar
      estimate resulted from gel filtration under nondenaturing conditions, followed by
      ELISA. However, lymphocyte membrane-extracted and soluble CD44 had different
      mobilities after treatment with neuraminidase plus O-glycosidase, and the core
      protein of soluble CD44 might be 17 to 20 kDa smaller than that of CD44 on
      lymphocyte membranes. Furthermore, an Ab to cytoplasmic residues of CD44 failed
      to recognize soluble CD44 recovered from the circulation or in lymphoma culture
      supernatants. These observations would be consistent with cleavage of CD44 from
      cell surfaces; and protease inhibitors slowed the loss of CD44 from cultured
      lymphomas. Serum CD44 levels were significantly reduced in immunodeficient
      CD17.SCID and BALB/c.Xid mice, and elevated in tumor-bearing mice. Mild graft-vs
      host (GVH) reactions also resulted in increased concentrations of CD44, as did
      autoimmune disease in BXSB and MRL/lpr strains of mice. Serum with high
      concentrations of CD44 partially blocked the binding of one ligand, hyaluronate,
      to CD44-bearing hybridoma cells. The degree of inhibition was positively
      correlated with CD44 concentration. These findings indicate that substantial
      quantities of CD44 can be released into the circulation by cleavage from cell
      surfaces and that this process is markedly influenced by immune system activity
      and tumor growth. The material seemed to be intact and potentially functional.

PMID- 7523496
TI  - Signaling via CD7 molecules on human NK cells. Induction of tyrosine
      phosphorylation and beta 1 integrin-mediated adhesion to fibronectin.
AB  - We have previously reported that CD7 expressed on resting human NK cells is a
      signal-transducing molecule, which upon ligation with mAb induces a rapid
      increase in cytoplasmic free calcium, secretion of IFN-gamma, and augmented NK
      activity against K562 targets. We now demonstrate that Ab-mediated clustering of
      CD7 molecules on NK cells results in enhanced phosphorylation on tyrosine
      residues of intracellular proteins of 60, 70, 80, 97, and 120 kDa. In the
      presence of genistein, a specific inhibitor of protein tyrosine kinase, the
      enhanced level of tyrosine phosphorylation was blocked, indicating that CD7 may
      induce signaling via activation of tyrosine kinases. Cross-linking of CD7 or CD16
      molecules with primary and secondary Abs, as well as stimulation of NK cells with
      phorbol ester (PMA) or with calcium ionophore A23187 also induced beta 1 integrin
      mediated adhesion of these cells to fibronectin (FN)-coated plastic surfaces. In
      contrast, cross-linking of CD2 expressed on the surface of NK cells had no
      significant effect on NK cell adhesion to FN. This adhesion was not associated
      with up-regulation of expression of alpha 4 beta 1 or alpha 5 beta 1 FN receptors
      on NK cells, but it required an intact cytoskeleton. The CD7-induced adhesion to
      FN was mediated by alpha 4 beta 1 and alpha 5 beta 1 integrins, as it was
      partially blocked by FN connective segment-1 peptide (EILDVPST), the alpha 4 beta
      1-binding domain, as well as by RGD-containing peptides, the alpha 5 beta 1
      binding domain, but not by EILEVPST or RGE control peptides. NK cell binding to
      FN was also partially inhibited by mAb to alpha 4, alpha 5, and beta 1 integrins.
      The mechanism by which cross-linking of CD7 or CD16 on NK cells induced adhesion
      to FN appeared to involve both protein tyrosine kinase and protein kinase C,
      because this adhesion was blocked in the presence of either genistein or a
      protein kinase C inhibitor, staurosporin. Our data demonstrate that signals
      transduced via triggering of either CD7 or CD16 molecules are involved in the
      regulation of the functional activity of beta 1 integrins on NK cells.

PMID- 7523495
TI  - Prevention of anti-CD3 monoclonal antibody-induced thymic apoptosis by protein
      tyrosine kinase inhibitors.
AB  - The thymus gland is crucial for the formation of thymocytes of diverse TCR
      specificity. Recent studies have demonstrated that deletion (negative selection)
      of autoreactive thymocytes occurs through the process of apoptosis in which TCR
      activates cell death by DNA fragmentation. In addition, in vitro stimulation of
      thymocytes with anti-CD3 mAb, calcium ionophore, or glucocorticoids results in
      DNA fragmentation followed by cell death. The availability of various substances
      capable of inhibiting activation-induced programmed cell death of thymocytes may
      be used as a tool to help identify several important events occurring during the
      process of apoptosis. We investigated the effect of protein tyrosine kinase (PTK)
      inhibitors, herbimycin A and genistein, on thymocyte apoptosis induced by
      stimulation of anti-CD3 mAb or glucocorticoid. Anti-CD3 mAb stimulation resulted
      in removal of CD4+CD8+ thymocytes by DNA fragmentation. However, in PTK inhibitor
      pretreated thymocytes, there was a minimal deletion of double positive
      thymocytes. In contrast, PTK inhibitors did not prevent glucocorticoid-induced
      thymic apoptosis. Our results suggest that anti-CD3 mAb-induced thymic apoptosis
      depends on PTK activation via TCR, and that glucocorticoid-induced thymic
      apoptosis is PTK-independent.

PMID- 7523498
TI  - Clonal expansion but lack of subsequent clonal deletion of bacterial superantigen
      reactive T cells in murine retroviral infection.
AB  - Several studies have suggested that activation-induced apoptosis of Ag-specific
      CD4+ T cells leads to depletion of this subset during HIV infection. The
      bacterial superantigen, staphylococcal enterotoxin A (SEA), is known to induce
      activation-induced apoptosis in the TCR V beta-bearing CD4+ T cells in the
      periphery after clonal expansion of these cells. The murine retroviral model of
      AIDS (MAIDS), which is induced by LP-BM5 murine leukemia virus, shares many
      common features with HIV infection in humans, except that CD4+ T cells increase
      progressively in susceptible strains. In this study, we challenged SEA to MAIDS
      mice and examined whether this retrovirus affects the fate of the SEA-reactive
      CD4+ T cells in vivo. At 4 wk post-infection with LP-BM5 murine leukemia virus,
      clonal expression and subsequent deletion of SEA-reactive CD4+V beta 3+ T cells
      occurred normally after SEA administration, whereas in vitro proliferative
      responses were severely impaired. At 8 wk postinfection, the in vivo expansion of
      CD4+V beta 3+ T cells was evident, but not followed by clonal deletion, as late
      as 14 days after SEA administration. This expanding subset in the infected mice
      expressed the Fas Ag in the same amount as the same subset in uninfected
      controls. These findings suggest that activation-induced apoptosis of
      superantigen-reactive CD4+ T cells is interfered with in vivo during the course
      of MAIDS, which is not attributable to underexpression of the Fas Ag by the CD4+
      T cells.

PMID- 7523499
TI  - Expression of the inducible nitric oxide synthase. Correlation with
      neuropathology and clinical features in mice with lymphocytic choriomeningitis.
AB  - Nitric oxide (NO) synthesized by the cytokine-inducible enzyme, nitric oxide
      synthase (iNOS), is thought to be a key mediator in the host immune response to
      infection, in which it may have protective, as well as injurious, actions. We
      sought evidence for a role of NO in the pathogenesis of lymphocytic
      choriomeningitis by examining the cerebral expression of the iNOS gene in mice
      after intracranial inoculation of lymphocytic choriomeningitis virus. In
      euthymic, but not athymic, mice, elevated expression of iNOS mRNA was observed in
      the brain by day 5 and increased further to high levels by day 6 postinfection.
      Of the peripheral organs, only the spleen showed significant increases in iNOS
      mRNA at day 3 postinfection. In situ hybridization revealed that iNOS RNA
      expression was restricted to cells within the inflammatory infiltrates and in
      proximity to areas of lymphocytic choriomeningitis virus infection in the brain.
      Immunostaining for iNOS protein identified numerous positive cells within the
      inflammatory infiltrates present in the meninges and choroid plexus. Phenotypic
      analysis revealed the majority of the iNOS containing cells to be Mac-1 positive.
      T lymphocytes that belonged to the CD8+ and CD4+ subsets were negative for iNOS
      expression. The kinetics and distribution of cerebral iNOS expression in
      lymphocytic choriomeningitis are consistent with a major role for the iNOS/NO
      pathway in the pathogenesis of this immune-mediated neurologic disease.

PMID- 7523497
TI  - Differentiation of the T helper phenotypes by analysis of the methylation state
      of the IFN-gamma gene.
AB  - Th1 and Th2 CD4+ T cell clones have been defined by their ability to produce
      different lymphokines. However, the processes by which CD4+ T cells
      differentially regulate lymphokine gene expression have not been well defined. In
      this report, we demonstrate that the methylation status of a CpG dinucleotide
      contained within a TATA proximal regulatory element of the IFN-gamma promoter
      correlates with the transcription of the gene. In murine Th1 clones and two human
      CD4+ Th0 clones, this site is either completely or partially hypomethylated,
      whereas in murine Th2 clones this site is > 98% methylated. Treatment of murine
      Th2 clones with 5-azacytidine, an agent that inhibits methylation of the DNA,
      converts these cells to IFN-gamma producers. Additional targets for methylation
      outside the transcriptional control regions of the IFN-gamma genetic locus were
      found to be hypomethylated in Th2 cells but not in Th1 cells. Electrophoretic
      mobility shift assays (EMSA) revealed at least five distinct protein-DNA
      complexes that are formed with an oligonucleotide containing the IFN-gamma
      promoter TATA proximal regulatory element, and in vitro methylation of this site
      results in a loss of these three complexes. Furthermore, a comparison of nuclear
      extracts prepared from Th1 and Th2 clones revealed that the EMSA patterns were
      qualitatively similar but differed quantitatively. In addition, transient
      transfection of a murine IFN-gamma promoter-chloramphenicol acetyl transferase
      (CAT) gene construct into both Th1 and Th2 clones produced CAT activity that was
      not inducible by anti-CD3, indicating that hypomethylation per se of the promoter
      alone is not sufficient for inducible gene expression.

PMID- 7523502
TI  - Relationship of TSG-14 protein to the pentraxin family of major acute phase
      proteins.
AB  - TNF-stimulated gene-14 (TSG-14) encodes a secreted glycoprotein with significant
      sequence homology to C-reactive protein (CRP) and serum amyloid P component
      (SAP), members of the pentraxin family of acute phase proteins. TSG-14 mRNA was
      elevated in human FS-4 fibroblasts by treatment with TNF, IL-1, or bacterial LPS,
      and weakly by dexamethasone. Abs to recombinant TSG-14 immunoprecipitated a 42
      kDa protein from the culture supernatants of TNF- or IL-1-stimulated FS-4 cells.
      TSG-14 protein was also inducible in the Hep3B human hepatoma cell line by TNF,
      IL-1, IL-6, or dexamethasone. CRP protein, identified by immunoprecipitation of a
      25-kDa band with Abs to CRP, was induced in Hep3B cells by IL-1, IL-6, or
      dexamethasone. Immunoprecipitations with polyclonal Abs to TSG-14 and CRP
      suggested that the two proteins are immunologically cross-reactive. Appearance of
      TSG-14 protein was demonstrated in the serum of mice after injection with LPS. No
      TSG-14 mRNA was detected in the liver of LPS-injected mice, suggesting that
      hepatocytes are not the major site of TSG-14 synthesis. Thus, in the intact
      organism the main cellular sources of TSG-14 and classical acute phase proteins
      appear to be different.

PMID- 7523500
TI  - Selective inhibitory effects of the anticoagulant activated protein C on the
      responses of human mononuclear phagocytes to LPS, IFN-gamma, or phorbol ester.
AB  - Recent studies have shown that infusion of the anticoagulant protein, activated
      protein C (APC), can ameliorate many of the systemic effects of endotoxemia in
      experimental animals, although the mechanisms in this action are unknown. We
      investigated the effects of APC on the responses of blood monocytes, alveolar
      macrophages, and cells of the monocyte line, THP-1, to stimulation in vitro by
      LPS, IFN-gamma, or PMA. Mononuclear phagocyte (MO) activation was associated with
      rapid production of TNF-alpha, down-regulation of the glycophosphatidylinositol
      linked protein CD14 (the key MO receptor for complexes of LPS and LPS-binding
      protein responsible for intracellular signaling), and down-regulation of the
      related LPS-binding proteins CD11b and CD18. Addition of APC, but not the
      zymogen, PC, or active site-blocked APC, inhibited selected MO responses
      involving the CD14-dependent LPS-induced pathway of MO activation, or activation
      induced by IFN-gamma or PMA. Thus, APC inhibited the production of TNF-alpha and
      prevented down-regulation of membrane CD11b, CD14, and CD18, but had no effect on
      up-regulation of MHC class II, ICAM-1, or IL-2R, down-regulation of MO expression
      of another glycophosphatidylinositol-linked protein, CD59, or production of
      reactive oxygen intermediates. These data show that APC inhibits host cytokine
      production but maintains MO responses associated with adhesion, phagocytosis, and
      killing of Gram-negative bacteria, such that use of APC may be a logical and
      potent adjunctive therapy in select inflammatory diseases involving MO activation
      and damaging host cytokine overproduction.

PMID- 7523501
TI  - Synergistic cooperation between phorbol ester and IFN-gamma for induction of
      nitric oxide synthesis in murine peritoneal macrophages.
AB  - The role of protein kinase C (PKC) in the induction of nitric oxide (NO)
      synthesis in murine peritoneal macrophages was examined. Phorbol ester, a PKC
      activator, had no effect on NO synthesis by itself, whereas IFN-gamma alone had
      modest activity. When phorbol ester was used in combination with IFN-gamma, there
      was a marked cooperative induction of NO synthesis in a dose-dependent manner.
      This increase in NO synthesis was reflected as increased amount of inducible NO
      synthase (iNOS) mRNA, as determined by Northern blotting. The optimal effect of
      phorbol ester was shown at 6 h after treatment with IFN-gamma. Phorbol ester also
      induced the release of NO to the incubation medium by bacillus Calmette-Guerin
      infected peritoneal macrophages. Prolonged incubation of cells with phorbol
      ester, which down-regulates PKC activity, abolished the synergistic cooperative
      effect on NO production with IFN-gamma. In addition, such PKC inhibitors as
      staurosporin or polymyxin B reduced NO production induced by IFN-gamma plus
      phorbol ester. When the cells were treated with both actinomycin D and phorbol
      ester after IFN-gamma stimulation, more NO was produced and more iNOS mRNA was
      expressed than in the cells treated with actinomycin D alone. On the basis of
      these observations, we conclude that PKC might not be directly involved in the
      expression of NO synthase, but, instead, might be involved in the stabilization
      of the iNOS mRNA already expressed by the treatment of IFN-gamma.

PMID- 7523503
TI  - Serologic analysis of the mouse beta chemokine JE/monocyte chemoattractant
      protein-1.
AB  - Mouse monocyte chemoattractant protein-1 (MCP-1), previously termed JE, is a
      member of the beta chemokine gene family and a homologue of the human monocyte
      chemoattractant protein, MCP-1. Mouse rMCP-1 was used to immunize hamsters for
      the production of mAb. Seven mouse MCP-1-specific mAbs were characterized: two of
      these mAbs cross-reacted with the human MCP-1, as determined by ELISA. A
      sensitive and specific capture ELISA for MCP-1 quantitation, which allowed
      measurement of mouse MCP-1 levels in supernatants from cells stimulated with
      inflammatory agents, was developed. LPS-stimulated astrocytes produce the highest
      levels of MCP-1 (80 ng/ml); macrophages and mesangial cells produce lower levels
      of MCP-1 (2 to 14 ng/ml) after LPS stimulation. IL-1 and TNF-alpha stimulation
      also can induce low levels of MCP-1 production. Western blot analysis
      demonstrated that the predominant native form of mouse MCP-1 is a 30-kDa
      glycoprotein. Two mAbs (2H5 and 6C7) demonstrated dose-dependent neutralization
      of mouse MCP-1 chemotactic activity. To localize the epitope recognized by one of
      these neutralizing Abs, the mAb was used to bind a series of genetically
      engineered truncated variants of human MCP-1. The C-terminal residues 62 to 67 on
      human MCP-1 molecules seem to be critical to express the epitope recognized by
      the neutralizing 2H5 anti-MCP-1 mAb. However, multiple sites on the MCP-1
      molecule seem to be critical for bioactivity. Thus, these Ab reagents provide a
      useful tool to explore the biology of the mouse MCP-1 beta chemokine.

PMID- 7523504
TI  - Stem cell factor is a chemotactic factor for human mast cells.
AB  - The mast cell is one of the major effector cells in inflammatory reactions and
      can be found in most tissues throughout the body. During inflammation, an
      increase in the number of mast cells can be seen, e.g., in the intraepithelial
      cell layer after a provoked allergic reaction. Such accumulation probably
      requires directed migration of mature mast cells or their precursors. To study
      the migration of human mast cells we used as a model the human mast cell line,
      HMC-1, and stem cell factor-dependent (also referred to as mast cell growth
      factor or Kit ligand) cord blood-derived mast cells. The results show that stem
      cell factor is a potent chemotactic factor for human mast cells in vitro. The
      chemotactic response to SCF was found to be dose dependent, reaching a maximum at
      50 ng/ml. The activity of SCF could be blocked by anti-SCF Abs. We also tested
      the effect of different intercrines, i.e., IL-8, MIP-1 alpha, MIP-1 beta, RANTES,
      and MCAF (also referred to as monocyte chemotactic protein 1), on human mast cell
      migration. Only RANTES was chemotactic for in vitro-developed mast cells. None of
      the tested intercrines induced migration of HMC-1 cells. For migration, the mast
      cells were dependent on binding to an extracellular matrix protein. Thus, coating
      of the filters with fibronectin was required, whereas collagen or laminin did not
      promote migration. Adhesion of HMC-1 cells to fibronectin could also be shown in
      an adhesion assay. In addition, expression of receptors for fibronectin could be
      detected on the surface of the mast cells. These results show that SCF is not
      only a growth and differentiation factor for human mast cells in vitro but also a
      potent chemoattractant for such cells.

PMID- 7523506
TI  - Distinct but overlapping epitopes are involved in alpha 4 beta 7-mediated
      adhesion to vascular cell adhesion molecule-1, mucosal addressin-1, fibronectin,
      and lymphocyte aggregation.
AB  - The mouse CD8+ T cell lymphoma TK1 expresses high levels of alpha 4 beta 7
      integrin, which it can use to interact with multiple ligands including mucosal
      addressin-1 (MAdCAM-1), VCAM-1, and fibronectin. In addition, alpha 4 beta 7 can
      support TK1 cell aggregation. Here we have produced and characterized a panel of
      mAbs against alpha 4 beta 7 to define antigenic and functional epitopes
      associated with its distinct functions. One mAb, DATK32, is unique in recognizing
      an epitope specific to the alpha 4 beta 7 heterodimer. Furthermore, DATK32
      induces TK1 cell aggregation yet inhibits TK1 cell adhesion to MAdCAM-1, VCAM-1,
      and fibronectin. Considered as a whole, the panel of anti-alpha 4 beta 7 mAbs
      studied define unique patterns of inhibition for alpha 4 beta 7 binding to each
      of its defined molecular ligands. We conclude that alpha 4 beta 7 interactions
      with MAdCAM-1, VCAM-1, and fibronectin can be modulated by Ab binding to distinct
      epitopes and thus probably involve functionally separable, although physically
      overlapping binding sites on this multifunctional integrin. These findings are
      consistent with the general observation that integrins use distinct, potentially
      differentially regulated interaction sites for adhesion to multiple ligands.
      Extension of these concepts to alpha 4 beta 7 has important considerations for
      understanding the roles of this integrin in lymphocyte homing to mucosal sites
      and in cell-cell interactions during the immune response.

PMID- 7523507
TI  - Inducible binding to the c-fos serum response element during T cell activation is
      regulated by a phosphotyrosine-containing protein.
AB  - The proto-oncogene c-fos is an immediate-early gene, and one of the first genes
      transcribed after stimulation of most cells with a variety of ligands. Fos
      expression may be a pivotal event in converting ligand-receptor interactions at
      the membrane into functional modulation of cell phenotype. The serum response
      element (SRE) in the c-fos regulatory region participates in induction of
      transcription by various growth factors and by phorbol esters and subsequent
      squelching of transcription. We show that an inducible protein complex (Band A)
      binds to SRE DNA within 10 min after mitogenic stimulation of human PBL-T, and
      becomes nondetectable by 60 min. Band A contains the serum response factor plus
      additional factor(s). A protein that is phosphorylated on a tyrosine residue in
      resting PBL-T suppresses binding of a component of Band A to the SRE motif. Upon
      stimulation of the cells, this protein no longer prevents binding of DNA by Band
      A, and suppression of binding is restored within 30 min. The phosphorylated
      tyrosine residue itself is important for the protein-protein interaction.

PMID- 7523508
TI  - Immunological tolerance to a defined myelin basic protein antigen administered
      intrathymically.
AB  - To explore the mechanisms responsible for the development of tolerance to
      allografts after intrathymic (IT) injection of alloantigen, the well-defined
      model of experimental autoimmune encephalomyelitis (EAE), which mimics the human
      autoimmune disease multiple sclerosis, was used. This inflammatory neurologic
      syndrome is initiated by myelin basic protein (MBP)-reactive CD4+ T lymphocytes
      restricted to self-MHC class II molecules. Naive adult, EAE-susceptible Lewis
      (RT1(1) rats were treated IT, i.v., or i.p. with a single dose (100 micrograms)
      of guinea pig-myelin basic protein (GP-MBP 1-176) in PBS plus 1 ml rabbit anti
      rat lymphocyte serum i.p. Twenty-one days later, all rats were challenged by
      intradermal hind footpad injections of 50 micrograms GP-MBP in PBS emulsified in
      CFA. Only IT, but not i.p. or i.v., administration of GP-MBP plus anti-lymphocyte
      serum conferred marked resistance to a subsequent systemic challenge of GP-MBP,
      as demonstrated by the prevention of weight loss and paralysis characteristic of
      EAE. The IT administration dramatically decreased the size and number of
      histologic perivascular infiltrates observed per visual field in spinal cord of
      the tolerant animals and decreased GP-MBP-specific T lymphocyte in vitro
      proliferation (p < 0.01), whereas proliferation to a nonspecific mitogen (Con A)
      was not altered. With the addition of rIL-2, the decreased Ag-specific
      proliferative responses of IT-treated animals increased to control levels.
      Adoptive transfer of 100 x 10(6) splenocytes from tolerant hosts i.v. to naive
      syngeneic Lewis rats challenge with 100 micrograms GP-MBP in CFA had no effect on
      clinical or histologic EAE. Exposure of MBP to maturing thymocytes results in
      functionally immunounresponsive lymphocytes and prevention of autoimmune EAE.

PMID- 7523505
TI  - A region of the third variable loop of HIV-1 gp120 is recognized by HLA-B7
      restricted CTLs from two acute seroconversion patients.
AB  - HIV-1 envelope-specific CTL clones were isolated from the peripheral blood of two
      patients from within weeks of seroconversion. These clones were CD8+ and
      restricted by the HLA-B7 molecule. The minimum epitope recognized by the clones
      was determined to be the 30-amino acid (aa) sequence RPNNNTRKSI within the third
      variable (V3) loop of the envelope glycoprotein gp120. The aa sequence of this
      epitope is consistent with the motif found in naturally processed peptides eluted
      from HLA-B7 molecules. This region of the V3 loop is reasonably well conserved
      among clade B and some nonclade B isolates of HIV-1, especially at the anchor
      residues that determine binding to the HLA-B7 molecule. Using peptides based upon
      virus sequences present within each patient, we determined that autologous
      viruses were recognized by the clones, and we detected no escape variants from
      the initial clonal response during the acute phase of infection. Interestingly, a
      serine to arginine change at position 9 of the epitope abrogated clone
      recognition in one of the patients. This aa change is one factor that has been
      associated with a change from a nonsyncytium-inducing to a syncytium-inducing
      phenotype of HIV-1, raising the possibility that in HLA-B7-expressing patients,
      escape from this clonal CTL response and a change in viral phenotype may be
      linked. This study demonstrates that human CTL can be generated against sequences
      within the third variable loop of HIV-1 gp120. Because multiple vaccine
      strategies are based upon the V3 loop of HIV-1 gp120, this defined epitope can be
      exploited in determining the ability of certain vaccines to stimulate a CTL
      response in a select population of individuals.

PMID- 7523509
TI  - Cell surface P- and E-selectin support shear-dependent rolling of bovine
      gamma/delta T cells.
AB  - The vascular selectins P- and E-selectin are inducible adhesion proteins
      expressed by endothelial cells that have been shown to support shear-dependent
      rolling of myeloid cells. This interaction is thought to be a prerequisite event
      for subsequent steps, such as tight adhesion/aggregation and transendothelial
      cell migration, involved in the accumulation of leukocytes into tissues. Certain
      lymphocyte subsets have also been shown to bind the vascular selectins, but the
      importance of this interaction in mediating shear-dependent rolling, as described
      for myeloid cells, has not been demonstrated. We expand on our earlier
      observation that bovine gamma/delta T cells bind E-selectin by showing that this
      interaction leads to a reproducible rolling event in assays done under shear
      forces that approximate those that occur in vivo. E-selectin, expressed by L cell
      transfectants or cytokine-stimulated human and bovine endothelial cells, equally
      supports the shear-dependent rolling interaction. The lymphocyte adhesion
      proteins L-selectin, CD44, and CD2 do not contribute to this event. Neuraminidase
      treatment of the gamma/delta T cells or addition of EDTA to the assay completely
      blocks the rolling interaction. We further show for the first time that P
      selectin expressed by thrombin-activated platelets or a soluble P-selectin/human
      Ig chimera specifically binds gamma/delta T cells. The P-selectin interaction is
      similar to the rolling event mediated by E-selectin--it requires divalent cations
      and sialic acid on the lymphocyte, it lacks involvement of L-selectin and CD44,
      and rolling occurs under physiologic shear conditions. These results provide the
      documentation that the vascular selectins can support shear-dependent rolling of
      a lymphocyte subset and that P-selectin mediates the adhesion of gamma/delta T
      cells.

PMID- 7523510
TI  - Endothelial cell-induced resistance to cyclosporin A in human peripheral blood T
      cells requires contact-dependent interactions involving CD2 but not CD28.
AB  - The ability of cultured human endothelial cells (EC) to activate resting T cells
      depends on signals provided by EC that augment T cell IL-2 synthesis. EC-mediated
      augmentation of IL-2 secretion by PHA-activated T cells is resistant to
      inhibition by cyclosporin A (CsA) or by ascomycin. Specifically, the 50%
      inhibitory dose of these drugs is increased over 100-fold in the presence of EC.
      Although rapamycin also inhibits IL-2 secretion, there is no effect of EC on the
      sensitivity of T cells to this drug. Resistance to CsA requires cell contact
      between the EC and T cells and develops 8 h after initiation of coculture.
      Experiments with blocking Abs implicate T cell CD2 and its endothelial cell
      ligands, both LFA-3 and CD59, but not T cell CD28 and its putative ligands, in EC
      induced resistance to CsA. However, CD2 signals are not sufficient to induce
      resistance to CsA, and other EC signals remain to be identified. These
      observations suggest that interactions of graft EC with host T cells may
      contribute to CsA-resistant reactions in vivo.

PMID- 7523511
TI  - In vivo CD4+ lymph node T cells from lpr mice generate CD4-CD8-B220+TCR-beta low
      cells.
AB  - Double-negative CD4-CD8-T cells (DNT) have been shown to be the major population
      of T cells responsible for the massive lymphadenopathy associated with the early
      onset of the lupus-like syndrome in mice bearing the lpr gene. Previously, we
      demonstrated that these cells do not proliferate in the peripheral lymphoid
      organs that they invade; furthermore, we showed that a wide range of CD4 Ag
      expression was observed on lymph node CD4+ T cells. In this study, we used an in
      vivo transfer system to analyze the progeny of CD4+ T cells from B6-lpr/lpr mice.
      Purified CD4+ T cells injected into B6 nude mice are able to generate DNT cells;
      furthermore, phenotypic and functional characterizations of the DNT cells
      generated in vivo show that they share the same properties as DNT cells from B6
      lpr/lpr mice. We also show that, after in vitro bromodeoxyuridine incorporation,
      only CD4+ cells cycle. From these studies, we conclude that the
      lymphoproliferation occurs at the CD4+ stage and that down-regulation of this Ag
      probably is followed by arrest of the cell cycle.

PMID- 7523513
TI  - Human peripheral blood dendritic cell subsets. Isolation and characterization of
      precursor and mature antigen-presenting cells.
AB  - Dendritic cells (DC) are the major APC capable of stimulating resting T cells in
      human peripheral blood (PB). Recent evidence suggested that various subsets of DC
      and monocytes might circulate in human PB, but their exact phenotype and function
      had not been delineated. We have previously characterized a population of human
      PB DC precursors that express the myeloid marker CD33, but not the monocyte
      marker CD14. To identify and characterize further functional myeloid APC subsets,
      triple color FACS analysis and sorting was used. A CD33dimCD14dimCD16+ monocyte
      subset, with similar APC function but less efficient accessory function than
      CD14bright monocytes, was isolated. In addition to the CD33+CD14dimCD16- DC
      precursors, a smaller population (0.1 to 0.2% of PBMC) of CD33brightCD14dimCD16-
      cells with potent APC function was identified. This DC population expressed
      greater amounts of MHC class II, adhesion, and accessory molecules, and
      demonstrated a greater costimulatory capacity when freshly isolated than
      CD33dimCD14dim DC precursors, and therefore had the characteristics of mature,
      possibly tissue-derived DC. When freshly isolated, however, these DC did not
      express B7, and up-regulation of accessory function occurred after in vitro
      differentiation. These data demonstrate multiple circulating myeloid accessory
      and APC subsets in human PB. Phenotypic and functional differences suggest that
      they are at different stages of differentiation, and have specialized roles in Ag
      presentation in vivo. Furthermore, full functional DC differentiation, associated
      with B7 expression and the capacity to activate T cells maximally, is likely to
      occur only in specific physiologic circumstances.

PMID- 7523512
TI  - CD7 is associated with CD3 and CD45 on human T cells.
AB  - The CD7 cluster of mAb identifies a 40-kDa glycopolypeptide that is present on a
      major subset of human T cells. CD7 Ag mediates an accessory pathway of T cell
      activation in that cross-linked CD7 mAb are mitogenic, and signals delivered via
      CD7 Ag stimulate integrin-mediated adhesion. We have found that the CD7 molecule
      is associated with a tyrosine kinase whose major substrate is CD45. In vitro
      phosphorylation of CD7, CD3, or CD45 immunoprecipitates prepared from lysates of
      human T cells showed a similar pattern of multiple phosphorylated polypeptides;
      in addition, these immunoprecipitates phosphorylated a tyrosine kinase-specific
      peptide. Surface-iodinated T cells were lysed and immunoprecipitated with CD7,
      CD3, and CD45 mAb. Bands characteristic of CD45 and CD3 were identified in CD7
      immunoprecipitates. Confirmation of an association of CD7 with CD3 and CD45 was
      obtained from Western blotting and fluorescence resonance energy transfer
      experiments. Furthermore, we provide evidence using immunoprecipitation and
      Western blotting that CD7 exists as a homodimer. These data support the
      hypothesis that CD7 exists in an oligomeric complex with CD3/TCR, the protein
      tyrosine phosphatase CD45, and a tyrosine kinase, thereby providing a physical
      basis for the accessory role of the CD7 molecule in T cell activation.

PMID- 7523514
TI  - Beta 2-microglobulin independent presentation of exogenously added foreign
      peptide and endogenous self-epitope by MHC class I alpha-chain to a cross
      reactive CD8+ CTL clone.
AB  - CD8+ T cells recognize antigenic peptides in the context of MHC class I molecules
      that encompass two distinct polypeptide chains, the MHC-encoded alpha-chain and
      the non-MHC-encoded beta 2-microglobulin (beta 2-m). The beta 2-m is considered
      essential for the stability and function of the MHC class I peptide complex and,
      hence, for peptide presentation to CD8+ T cells. In this study, we describe
      peptide presentation by macrophages from beta 2-m-deficient mice to a CD8+ CTL
      clone tht cross-recognizes an H-2Db-restricted peptide of the mycobacterial heat
      shock protein 60 (hsp60) and a self-peptide presented by IFN-gamma-stressed
      macrophages. Specific lysis of stressed or hsp60 peptide-pulsed beta 2-m-/-
      macrophages was inhibited by the nucleoprotein peptide with high affinity to H
      2Db. Brefeldin A, a known inhibitor of MHC class I processing, interfered with
      lysis of IFN-gamma-stressed, but not of hsp60 peptide-pulsed, beta 2-m-/-
      macrophages. The hsp60 peptide failed to stimulate surface expression of H-2Db in
      beta 2-m-/- macrophages, and slightly increased MHC class I expression in the
      transporter mutant cell line RMA-S, as detected by cytofluorometry. We concLude
      that presentation of endogenously processed cytosolic epitopes and exogenously
      added foreign peptides by the MHC class I alpha-chain can occur independent from
      beta 2-m. Presumably, H-2Db peptides, but not H-2Kb peptides, have the capacity
      to induce and/or stabilize surface expression of a small number of MHC class I
      alpha-chains, and this low density is sufficient for recognition by CD8+ CTL,
      although it need not be detected by serologic means.

PMID- 7523515
TI  - Murine VCAM-1. Molecular cloning, mapping, and analysis of a truncated form.
AB  - Vascular cell adhesion molecule-1 (VCAM-1) is a member of the Ig superfamily that
      shows increased expression in a number of pathologic conditions. The role of VCAM
      1 in human disease remains undefined and murine models are being extensively
      studied to help define the importance of VCAM-1 in inflammatory disorders. We
      have cloned and characterized the murine Vcam1 gene including 3 kb of 5'-flanking
      sequences and mapped the gene to chromosome 3 near Amy1. cDNA clones isolated
      from a stimulated hepatic library were found to encode a truncated form of VCAM-1
      (T-VCAM-1) which contains Ig domains 1 through 3 and has a unique alternative
      carboxyl terminus. This form arises by alternative splicing. High level
      expression of T-VCAM-1 in transfected L cells was sufficient to support adhesion
      of lymphocytes, and this adhesion was blocked by Abs to VCAM-1. Treatment of
      transfected COS cells with phospholipase C led to reduced levels of T-VCAM-1 on
      the cell surface consistent with glycosylphosphatidylinositol linkage. Northern
      blot analysis showed that mRNA for T-VCAM-1 is inducible in multiple tissues
      after stimulation with endotoxin. Both forms of VCAM-1 were expressed in cultured
      endothelial, fibroblast, and aortic smooth muscle cells, whereas neither form was
      observed in monocyte- and lymphocyte-derived lines. Differential regulation of
      both forms of VCAM-1 was observed in the three different cell types that are
      present in the vessel wall. Thus, expression of VCAM-1 is restricted and
      controlled at the level of transcription and by alternative splicing.

PMID- 7523516
TI  - Bw4-reactive and Bw6-reactive antibodies recognize multiple distinct HLA
      structures that partially overlap in the alpha-1 helix.
AB  - Bw4 and BW6 epitopes are expressed by mutually exclusive sets of HLA-B alleles
      and some HLA-A and HLA-C alleles. To test whether antithetical structures are
      required to express Bw4 and Bw6 epitopes, we measured binding of Bw4-reactive and
      Bw6-reactive alloantibodies and mAbs to HLA-B7 variants. A triple substitution of
      HLA-B7 alpha-1 helix residues 80, 82, and 83 created Bw4 and destroyed Bw6
      epitopes detected by alloantibodies and mAbs. Both Bw4-reactive and Bw6-reactive
      mAbs competed for binding to HLA-B7 variants with single substitutions at
      residues 82 and 83. Substitutions of residues H93 and D119 which form a salt
      bridge in HLA-A2 also permitted binding by both Bw4-reactive and Bw6-reactive
      mAbs, suggesting that Bw4 and Bw6 epitopes are conformationally dependent. Six
      Bw4-reactive mAbs showed four distinct patterns of binding to HLA-B7 variants.
      Detailed analysis of 74 HLA-B7 single-residue variants showed that Bw6-reactive
      SFR8-B6 binding was prohibited by mutations altering the distal end of the alpha
      1 helix and the nearby connecting loop. In contrast, Bw6-reactive BB7.6 binding
      required both alpha-1 and alpha-2 helix residues. Thus, Bw4-reactive and Bw6
      reactive Abs recognize multiple distinct HLA structures that partially overlap in
      the alpha-1 helix. As both Bw4 and Bw6 epitopes are expressed by some HLA-B7
      variants, mutually exclusive expression of Bw4 and Bw6 epitopes in naturally
      occurring HLA class 1 molecules may reflect evolutionary pressure.

PMID- 7523518
TI  - Alternatively processed human E-selectin transcripts linked to chronic expression
      of E-selectin in vivo.
AB  - E-selectin, also known as endothelial leukocyte adhesion molecule-1 (ELAM-1), is
      transiently expressed on endothelial cells in response to inflammatory cytokines
      such as IL-1 and TNF-alpha and mediates adhesion of leukocytes. The genomic
      structure of E-selectin is highly conserved and includes multiple polyadenylation
      signals and a number of AUUUA transcript destabilizing elements within the 3'
      untranslated region (UTR). Anchored-PCR analysis indicates that all three
      polyadenylation signals within the human E-selectin 3'-UTR are indeed functional,
      and three forms of E-selectin transcripts (Types I, II, and III) generated by
      differential usage of these polyadenylation signals were detected in both
      cytokine-stimulated primary human endothelial cells and human skin tissue
      cultures. Although the longest transcript (Type III) is the most abundant form
      found in cytokine-stimulated human endothelial cells and human skin tissue
      cultures in vitro, only the shortest transcript (Type I) is detected in human
      dermal biopsies expressing cell surface E-selectin. Interestingly, the Type I E
      selectin transcript lacks six of the mRNA destabilizing elements that are thought
      to mediate rapid degradation of the corresponding mRNA. In agreement with the
      absence of these mRNA decay signals, we determined that the Type I E-selectin
      transcript is more stable than the full-length Type III E-selectin transcript in
      an in vitro chimeric mRNA stability assay. Therefore, the presence of only the
      Type I transcript in skin biopsies of chronic inflammatory lesions suggests that
      differential polyadenylation of E-selectin transcripts may provide the molecular
      basis for the observed chronic expression of E-selectin in human dermal
      disorders.

PMID- 7523517
TI  - Differential effects of blockade of CD28-B7 on the development of Th1 or Th2
      effector cells in experimental leishmaniasis.
AB  - Infection of inbred strains of mice with Leishmania major is a well-characterized
      model for analysis of the development of effector CD4+ subsets of the Th1 and Th2
      types in vivo. We co-administered a fusion protein, CTLA4Ig, that blocks the CD28
      B7 costimulatory pathway important for optimal T cell activation, to assess the
      relative role for this pathway during maturation of Th1 and Th2 cells in vivo.
      Surprisingly, CTLA4Ig administered within the first week of infection completely
      abrogated progressive disease in susceptible BALB/c mice while having no effect
      on the protective immune response developed by resistant C57BL/6 mice. The
      protective effect in BALB/c mice was increasingly lost if administration of
      CTLA4Ig was delayed longer than 1 wk after infection. As in other protective
      interventions used in this model, control of infection was associated with down
      regulation of IL-4 mRNA transcripts in lymph node cells recovered 5 wk after
      infection together with abrogation of IgE production and enhanced parasite
      specific IgG2a relative to IgG1. Although a single dose of CTLA4Ig was
      protective, sustained delivery abolished the capacity of BALB/c mice to contain
      infection, suggesting that costimulation through this pathway is required at
      later stages of the immune response. Taken together, the data demonstrate that
      the priming of Th2 cells is more dependent upon the CD28-B7 pathway than the
      priming of Th1 cells, and suggest that the development of Th subsets in vivo may
      be influenced by limiting CD28-B7 costimulation.

PMID- 7523519
TI  - L-selectin and very late antigen-4 integrin promote eosinophil rolling at
      physiological shear rates in vivo.
AB  - Adherence of eosinophils to vascular endothelium and their accumulation at sites
      of allergen challenge are hallmarks of allergic inflammation. However, the
      molecular mechanisms mediating eosinophil adhesion under conditions of blood flow
      are not well understood. The present studies were performed to identify the
      receptors on human eosinophils involved in initiating adhesion to activated
      endothelium at physiologic shear rates in vivo. We have compared the relative
      contribution of L-selectin, VLA-4 (CD49d), and CD18 integrins in mediating
      eosinophil adhesion to microvascular endothelial cells in the rabbit mesentery by
      using intravital video microscopy. Eosinophils were found to roll in venules, but
      not arterioles, and this rolling could be stimulated by activation of endothelium
      with IL-1. In contrast to neutrophil rolling, which is predominantly L-selectin
      dependent, eosinophil rolling was mediated by L-selectin, and also VLA-4. mAbs to
      L-selectin and VLA-4 alpha, but not CD18, significantly inhibited eosinophil
      rolling in vivo. The inhibition of VLA-4-mediated eosinophil rolling was not
      caused by modulation of eosinophil L-selectin or CD18 expression. This inhibition
      also was not caused by nonspecific inhibitory effect of the Abs studied, because
      the anti-VLA-4 mAbs inhibited eosinophil (VLA-4+) but not neutrophil (VLA-4-)
      rolling in the mesenteric venules. These results demonstrate that early events of
      eosinophil adhesion, i.e., rolling, are mediated by multiple adhesion receptors,
      including L-selectin and VLA-4, at physiologic shear rates in vivo.

PMID- 7523520
TI  - Macrophage-inactivating IL-13 suppresses experimental autoimmune
      encephalomyelitis in rats.
AB  - Experimental autoimmune encephalomyelitis (EAE) is initiated by myelin basic
      protein (MBP)-specific CD4+ T cells of the Th1 phenotype that subsequently
      trigger the invasion of monocytes/macrophages into the brain. In this study, we
      evaluated the potential of human recombinant (hr) IL-13 to exert a protective
      effect on the development of EAE in Lewis rats. hrIL-13 is found to be a potent
      in vitro modulator of various rat macrophage functions, including an inhibition
      of the production of the proinflammatory cytokines IL-1 beta and TNF, and a
      simultaneous enhancement of MHC class II and CD4 receptor expression.
      Furthermore, hrIL-13 displayed a slight, but highly reproducible, inhibitory
      effect on the in vitro proliferative responses of encephalitogenic MBP-specific T
      cells stimulated in the presence of thymic APCs. Upon in vivo application of hrIL
      13-secreting vector cells into MBP-immunized animals, the cytokine was capable of
      markedly suppressing the development of EAE, as assessed by a reduction of the
      mean duration, severity, and incidence of disease. This suppression of disease
      coincided with an only minimal reduction of MBP-directed T cell autoreactivity
      and no alteration in MBP-specific autoantibody production. We infer from these
      results that a strictly Th1-initiated immune disease can be attenuated
      efficiently by the administration of a cytokine that primarily targets cells of
      the macrophage/monocyte lineage and seems to exert no undesirable general
      suppression on either T cell or B cell immunoreactivity in vivo.

PMID- 7523523
TI  - Purification of human basophils by density and size alone.
AB  - Basophils typically account for approximately 1% of the white cells in peripheral
      blood. We have developed a unique method for purifying basophils from whole blood
      of normal subjects to at least 95% purity. Basophils are separated from other
      cell types by density-dependent sedimentation in Percoll and cell sorting, based
      solely on their size and granularity. The mean overall yield ranged from 5% to
      28%. The procedure is typically completed within 4 h. The highly purified
      basophils obtained are functionally competent and morphologically intact. They
      release histamine in response to Fc epsilon RI-mediated stimulation, express Fc
      epsilon RI and BSP-1 ligand as analyzed by flow cytometry, and exhibit the known
      characteristic ultrastructural features of basophils by electron microscopy. This
      procedure avoids positive-selection antibodies that might perturb receptors on
      basophils or negative-selection antibodies that might activate other cell types,
      and can be used to obtain basophils for studies in vitro.

PMID- 7523521
TI  - HIV-1 suppression of hematopoiesis in vitro mediated by envelope glycoprotein and
      TNF-alpha.
AB  - Dysmorphic marrow morphology and bone marrow failure are common in AIDS patients,
      but the mechanism of HIV-1 effects on blood cell production is unclear.
      Experiments to test the susceptibility of hematopoietic progenitor cells to HIV-1
      infection have led to conflicting results. We found that hematopoietic colony
      formation by burst-forming units-erythroid and CFU-GM was equivalently inhibited
      by both active and heat-inactivated, noninfectious virus. Inhibition was
      dependent on the presence of macrophages and was not observed in cultures derived
      from highly enriched CD34+ cells. We hypothesized that TNF-alpha, produced by
      mononuclear phagocytes after contact with HIV-1 or gp120 and itself a potent
      suppressor of hematopoiesis, might mediate this effect. The addition of anti-TNF
      alpha neutralizing Abs to marrow cultures abrogated inhibition by gp120 or virus.
      In contrast, neutralizing Abs to Il-4, IFN-alpha, and TGF-beta failed to improve
      colony formation. TNF-alpha was released from blood monocytes and marrow
      mononuclear cells stimulated by gp120. TNF-alpha is increased in the blood of
      patients with late stage AIDS and may mediate many of the symptoms of the
      disease. Our data do not support a requirement of direct infection of
      hematopoietic progenitor cells by HIV-1 for the inhibition of hematopoiesis in
      vitro. We propose instead an indirect mechanism of viral suppression of
      hematopoiesis as a result of TNF-alpha induction by virus or viral envelope
      glycoprotein. The importance of local TNF-alpha production in patients' marrow is
      amenable to clinical testing.

PMID- 7523522
TI  - Epitope specificity determines the ability of anti-Ro52 autoantibodies to
      precipitate Ro ribonucleoprotein particles.
AB  - Ro ribonucleoprotein particles (Ro RNPs) are evolutionarily conserved cytoplasmic
      complexes of unknown function. They are composed of several proteins and a small,
      RNA polymerase III-transcribed Ro or Y RNA. Abs directed against the protein
      moiety of Ro RNPs are often found in sera of patients suffering from certain
      autoimmune disorders. The association of one of the Ro proteins, a protein of 52
      kDa (Ro52), with Ro RNPs is still questionable. In this study, we have used anti
      Ro52 Abs isolated from autoimmune sera to locate the antigenic determinants of
      Ro52 and to analyze the correlation between regions of Ro52 recognized by these
      Abs and their ability to immunoprecipitate Ro RNPs. The results indicate that the
      autoimmune response against Ro52 is heterogeneous and that the exclusive
      recognition of certain epitopes does not result in immunoprecipitation of Ro
      RNPs.

PMID- 7523524
TI  - Human monoclonal anti-D secreting heterohybridomas from peripheral B lymphocytes
      expanded in the CD40 system.
AB  - Peripheral human B lymphocytes isolated from four immunised anti-D donors have
      been cultured in the CD40 system (Banchereau et al., 1991), prior to fusion to
      murine X63Ag8.653 plasmacytoma cells. High fusion efficiency was noted in all
      cases and immunoglobulin (IgG and IgM) was detected in nearly all heterohybrid
      containing wells. Only fusions using boosted donor lymphocytes generated specific
      anti-D secreting hybrids. A short period of culture of committed B cell
      precursors in the CD40 system before fusion appears to be both adequate and
      efficient in permitting generation of specific antibody-secreting hybrids.

PMID- 7523525
TI  - Enzyme immunoassay (ELISA) for the evaluation of antibodies directed to the CD4
      receptor-binding site of the HIV gp120 molecule.
AB  - The interaction between the HIV envelope glycoprotein gp120 and the CD4 molecule
      is probably the most important primary event determining HIV infection.
      Reactivity with the native viral envelope has been difficult to measure due to
      the lack of gp120 ligand purified directly from primary virus cultures. We have
      developed an ELISA, utilizing Galanthus nivalis agglutinin (GNA) which
      selectively binds native HIV envelope gp120 in culture medium. The GNA-based
      ELISA eliminates the need for isotope-labelled reagents, live cells and
      recombinant non-natively glycosylated envelope proteins and offers an easy way of
      using gp120 directly from crude HIV culture medium. The reactivities of sera from
      several categories of HIV infected individuals were assayed for inhibition of the
      HIV-1 gp120-CD4 binding. 19/32 (59.3%) sera from asymptomatic individuals and
      7/10 (70%) sera from ARC/AIDS patients blocked the CD4-gp120 binding. 20 serum
      samples from uninfected individuals showed a gp120-CD4 interaction blocking
      capacity of 0-15%. Two monoclonal antibodies, T4.2 directed to CD4 and 1171
      directed to the CD4 binding site of gp120 were used as positive controls. Both
      Mabs inhibited CD4-gp120 binding by 66-90%.

PMID- 7523526
TI  - A fluorescent cellular adhesion assay using insect cell produced human VCAM1.
AB  - Activated endothelium and some dendritic cells express the adhesion molecule
      VCAM1, a member of the immunoglobulin gene superfamily. Mononuclear leukocytes
      display the integrin VLA4 that functions as a counterreceptor for VCAM1. The
      interaction of VCAM1 with VLA4 mediates cell to cell adhesion events believed to
      be important regulators of inflammation, cancer cell metastasis, and
      atherosclerosis. This report describes the development of a fluorescent adhesion
      assay that specifically measures T cell adhesion to recombinant human VCAM1
      (rVCAM1) expressed in a baculovirus expression vector system (BEVS). We describe
      a simple and rapid protocol to partially purify non-denatured rVCAM1 from insect
      cell membrane preparations (VCAM1 infected Sf9 cells). Jurkat cells, a T cell
      line expressing VLA4, specifically adhered to the rVCAM1 membrane preparations
      coated onto 96-well plates. Jurkat cells did not adhere to control membrane
      preparations that lacked rVCAM1 protein. Both unstimulated and IL-2 stimulated
      Jurkat cells displayed functional VLA4 capable of binding to immobilized rVCAM1.
      Monoclonal antibodies recognizing either VCAM1 (E1/6, BBA6) or VLA4 (HP2/1)
      blocked specific VCAM1/VLA4 adhesion, whereas a monoclonal antibody to the alpha
      chain of LFA1 did not block adhesion. The methods described here could be applied
      to develop similar functional assays for other cell surface
      receptors/counterreceptors expressed in a BEVS.

PMID- 7523528
TI  - Prolongation of action of local anaesthetic by a possible complexation: clinical
      trials.
AB  - Long lasting pain relief for patients of malignancy involving head, neck, face
      and patients of trigeminal neuralgia was sought by the use of lignocaine with
      addition of complexing agents. Five patients with severe intractable pain of
      malignancy involving the trigeminal (V cranial) nerve mainly the maxillary and
      mandibular divisions, two patients of trigeminal neuralgia with trigger zone in
      maxillary division were treated. Remarkable prolongation of action of pain relief
      up to 6 weeks could be achieved. The recurred pain was also of less severity
      especially radiation was less. An explanation of the possible mechanism is
      offered.

PMID- 7523527
TI  - Measurement of mRNA for E-selectin, VCAM-1 and ICAM-1 by reverse transcription
      and the polymerase chain reaction.
AB  - Stimulation of cultured human umbilical vein endothelial cells by cytokines such
      as interleukin-1 and tumour necrosis factor induces de novo synthesis and
      expression of the adhesion molecules E-selectin, vascular cell adhesion molecule
      1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In general,
      alterations in cell surface expression of these molecules are known to be related
      to increased gene transcription and altered levels of mRNA. The extension of
      these observations to the study of inflammatory processes in different human
      organs necessitates the development of techniques for the quantification of mRNA
      in small tissue samples. Here we present a method for the quantification of mRNA
      for E-selectin, VCAM-1 and ICAM-1 using reverse transcription and the polymerase
      chain reaction (RT-PCR). For each molecule of interest a mutant RNA was
      synthesised consisting of the wild-type sequence deleted of 15-20 bases. The
      mutant and wild-type RNA sequences are recognised by the same primers, and can
      therefore be amplified competitively in the same tube by RT-PCR. As the mutant
      and wild-type RNAs compete for the primers, the amount of wild-type RNA can be
      determined by the size of the dominant product that results after addition of
      known quantities of mutant RNA. Using this detection and quantification method we
      have examined the dose dependency and time course of mRNA accumulation following
      TNF-alpha stimulation of HUVEC. Similar time-courses of E-selectin, ICAM-1 and
      VCAM-1 mRNA accumulation were observed by competitive RT-PCR as by laser
      densitometry of Northern blots. Finally we were able to show that the technique
      could measure changes in levels of mRNA for these three molecules in human skin
      biopsies taken at different times during the development of a delayed
      hypersensitivity response to tuberculin purified protein derivative. This
      technique should be useful for the study of adhesion molecule mRNA in small
      tissue culture samples and in biopsies.

PMID- 7523530
TI  - Comparative cytokine release from human monocytes, monocyte-derived immature mast
      cells, and a human mast cell line (HMC-1).
AB  - To obtain further information regarding the role of cytokines during mast cell
      differentiation, we have investigated changes of cytokine secretion in mast cells
      developing from the human peripheral blood monocytic cell fraction during culture
      with fibroblast-derived conditioned media. The influence of stem cell factor and
      an antibody to the respective receptor in our culture system was studied as well.
      Interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)alpha
      were spontaneously secreted by cultured cells at day 1 and decreased markedly by
      day 14. Similar changes occurred also during culture with stem cell factor and
      were partially abrogated by an anti-receptor antibody. IL-8 was secreted at a
      high level throughout the culture, whereas no spontaneous secretion of IL-2, IL
      3, IL-4, and IL-7 was measured at all. Upon stimulation with phorbol myristate
      acetate and A23187, cultured cells showed substantially more release of IL-3 and
      TNF-alpha after 14 d of culture, compared to peripheral blood monocytic cells.
      Preformed TNF-alpha was found in one of three monocytic cell preparations from
      peripheral blood, but not in monocytic cell-derived mast cells. During mast cell
      differentiation, cytokines from monocytic cells are therefore downregulated while
      the cells assume a pattern typically found in mast cells.

PMID- 7523529
TI  - Mutations of keratin 9 in two families with palmoplantar epidermolytic
      hyperkeratosis.
AB  - The hereditary palmoplantar keratodermas are a heterogeneous group of diseases
      unified by thickening of the stratum corneum of the palms and soles with
      consequent painful fissuring, discomfort on pressure, and resultant disability.
      One of the histologic patterns underlying palmoplantar hyperkeratosis is that of
      epidermolytic hyperkeratosis. Because that histologic pattern has been found in
      its generalized form to be due to keratin gene mutations, we assessed the
      inheritance of the form localized to the palms and soles. In each of two families
      studied, the mutant gene causing the disease is linked strongly to the chromosome
      17 cluster of genes encoding type I keratins, and mutations are present in the
      conserved helix initiation region of keratin 9 in affected members of both
      kindreds. These data, as well as those generated recently by others, indicate
      that keratin gene mutations may underlie not only the generalized phenotype but
      also this more localized phenotype of epidermolytic hyperkeratosis and suggest
      one mechanism by which skin diseases can achieve their characteristic
      localization.

PMID- 7523532
TI  - Expression of the B7/BB1 activation antigen and its ligand CD28 in T-cell
      mediated skin diseases.
AB  - Interactions of CD28 (on T cells) with its recently identified ligand B7/BB1 (on
      antigen-presenting cells) have been shown to activate T cells via a major
      histocompatibility complex/Ag-independent "alternative" pathway, leading to an
      amplification of T-cell-mediated immune responses. The in vivo relevance of these
      molecules for cutaneous immunity is presently unknown. These findings prompted us
      to study the expression of B7/BB1 and CD28 in normal human skin and in selected T
      cell-mediated inflammatory skin diseases. Biopsies were obtained from lesional
      skin of patients with allergic contact dermatitis, lichen planus, and, as
      control, from basal cell carcinoma and from healthy controls. Serial cryostat
      sections were stained with a panel of MoAbs directed against CD28, B7/BB1, CD3,
      CD1a, and KiM8 using immunohistochemistry (ABC technique). CD28 expression was
      observed in the majority of dermal and epidermal CD3+ T cells in contact
      dermatitis and lichen planus. In normal skin and basal cell carcinoma, CD28 was
      expressed only occasionally by perivascular T cells. In allergic contact
      dermatitis and lichen planus, B7/BB1-expression was found on dermal dendritic
      cells, on dermal macrophages, on Langerhans cells, focally on keratinocytes, and
      occasionally on dermal T cells. No B7/BB1 immunoreactivity was detected in normal
      skin and basal cell carcinoma. These findings indicate that T-cell-mediated skin
      diseases are accompanied by an influx of CD28+ T cells and an upregulation of
      B7/BB1 on cutaneous antigen-presenting cells, keratinocytes, and on some T cells.
      We speculate that "alternative" T cell-activation via the B7/CD28 pathway may
      contribute to the pathogenesis of these skin diseases.

PMID- 7523531
TI  - Increases in human epidermal DR+CD1+, DR+CD1-CD36+, and DR-CD3+ cells in allergic
      versus irritant patch test responses.
AB  - In an attempt to differentiate an allergic patch test response from an irritant
      response, we evaluated by flow cytometry the percentages of various epidermal
      cell populations isolated from allergen and irritant-treated patch test sites.
      Nine allergic individuals were patch tested with various allergens (Rhus,
      dinitrochlorobenzene [DNCB], or nickel chloride) and a vehicle control for 48 h.
      Eight additional individuals were patch tested with irritating chemicals (sodium
      lauryl sulfate or nonanoic acid) and with a vehicle control for 48 h. Epidermal
      cells, isolated from suction blisters, were double labeled for CD1/HLA-DR,
      CD3/HLA-DR, or CD36/HLA-DR cell surface markers and analyzed by flow cytometry to
      determine the percentage of various cell populations. A mean increase of 0.91 +/-
      0.3 in the percentage of DR+CD1+ Langerhans cells over the vehicle control patch
      test site was detected in allergen-positive patch test sites in allergic
      individuals, whereas a decrease of 0.19 +/- 0.2 in the percentage of DR+CD1+
      Langerhans cells from the vehicle control patch test site was detected in
      irritant-treated patch test sites. Epidermal cells from allergen-positive patch
      test sites also exhibited an increase of 5.2 +/- 1.8 in percentage of DR+CD1-
      cells over the vehicle control patch test site compared to an increase change of
      0.8 +/- 0.4 in epidermal cells isolated from irritant-treated patch test sites.
      We also found that DR+ cells that lacked the CD1 determinant expressed the
      macrophage/monocyte antigen CD36 (OKM5). Finally, a 2.3 +/- 0.8 increase in the
      percentage of DR-CD3+ cells over the vehicle control patch test site was observed
      in allergen-positive patch test sites compared to an increase of 0.2 +/- 0.2
      observed in irritant-treated patch test sites. These results demonstrate a
      significant increase in DR+CD1+, DR+CD1-CD36+, and DR-CD3+ epidermal cells in
      allergen-positive patch test sites compared to irritant patch test sites.

PMID- 7523534
TI  - Interleukin-5 messenger RNA and immunoreactive protein expression by activated
      eosinophils in lesional atopic dermatitis skin.
AB  - The main cellular sources of interleukin-5 (IL-5) are T lymphocytes and mast
      cells. Recently, IL-5 mRNA has been identified in eosinophils from patients with
      celiac disease, eosinophilic heart diseases, and asthma. In an attempt to
      determine whether IL-5 is generated by eosinophils in atopic dermatitis we have
      used i) in situ hybridization with 35S-labeled IL-5 RNA probe combined with
      immunohistochemistry using a monoclonal antibody (MoAb) (EG2) directed against
      the activated form of Eosinophil Cationic Protein (ECP) and ii) double
      immunostaining with anti-IL-5 MoAb and polyclonal anti-ECP antibody. We found
      that dermal eosinophils from lesional atopic dermatitis skin express IL-5 mRNA
      and protein. Moreover, highly purified blood eosinophils were also labeled with
      anti-IL-5 antibodies. The expression of IL-5 by eosinophils in atopic dermatitis
      might suggest an autocrine pathway of eosinophil differentiation and activation.

PMID- 7523535
TI  - Specific binding and lack of growth-promoting activity of substance P in cultured
      human keratinocytes.

PMID- 7523533
TI  - Application of angiogenic oligosaccharides of hyaluronan increases blood vessel
      numbers in rat skin.
AB  - Angiogenic oligosaccharides of hyaluronan were applied to the backs of young,
      adult male rats and the number of blood vessels, within a depth of 136 microns
      beneath the base of the epidermis, were evaluated. Application of hyaluronan
      oligosaccharides significantly increased the mean number of blood vessels/mm skin
      length in six of 11 treated rats when compared with controls. Application of
      radiolabeled hyaluronan oligosaccharides to skin of one rat demonstrated a
      penetration to a depth of approximately 800 microns, suggesting that the blood
      vessels beneath the epidermis would be exposed to the hyaluronan. Hyaluronan has
      previously been shown to stimulate endothelial cell proliferation; we demonstrate
      here that these hyaluronan oligosaccharides also specifically stimulate
      endothelial cell migration. This action of hyaluronan oligosaccharides may prove
      useful in retarding blood vessel paucity and degeneration observed during the
      ageing process and following radiotherapy.

PMID- 7523536
TI  - Safety and immunogenicity of a polyvalent Escherichia coli vaccine in human
      volunteers.
AB  - Since a limited number of O serogroups account for nearly 70% of bacteremic and
      meningitic Escherichia coli isolates, a polyvalent vaccine was made by
      conjugating a Pseudomonas aeruginosa exotoxin A carrier protein to the O
      polysaccharide of 12 serogroups of E. coli (O1, O2, O4, O6-O8, O12, O15, O16,
      O18, O25, O75). No serious reactions occurred in 88 vaccinees. Four-fold or
      greater increases in ELISA antibody levels over baseline were greatest (> 60% of
      vaccinees) for O1, O2, O6-O8 and O15; intermediate (approximately 50%) for O18
      and O75, and poorest (> or = 45%) for O4, O12, O16, and O25. Responses with
      functionally active opsonophagocytic antibody generally paralleled ELISA antibody
      responses. With the availability of a safe, immunogenic E. coli vaccine, active
      and passive immunization strategies merit further development as adjunctive
      treatment for E. coli bacteremia and neonatal meningitis.

PMID- 7523537
TI  - A large, antigenically conserved protein on the surface of Moraxella catarrhalis
      is a target for protective antibodies.
AB  - A monoclonal antibody (MAb) to Moraxella catarrhalis O35E bound to a surface
      exposed epitope of a proteinaceous antigen of this organism. The antigen,
      designated UspA, was present in every strain of the pathogen tested in a colony
      blot RIA. UspA had a molecular mass on SDS-PAGE that varied between 300 and 400
      kDa, depending on the individual M. catarrhalis strain. Passive immunization of
      mice with the UspA-reactive Mab enhanced pulmonary clearance of M. catarrhalis.
      Use of this Mab to screen a M. catarrhalis genomic DNA library permitted
      identification of a recombinant bacteriophage expressing the M. catarrhalis UspA
      protein. The recombinant UspA protein was used in Western blot analysis with sera
      from patients with M. catarrhalis pneumonia. Convalescent-phase sera but not
      acute-phase sera from these patients contained antibodies to this M. catarrhalis
      surface protein, indicating that M. catarrhalis strains growing in vivo express
      this molecule.

PMID- 7523538
TI  - Lymphoscintigraphic analysis of lymphatic abnormalities in symptomatic and
      asymptomatic human filariasis.
AB  - To obtain high-resolution radionuclide lymphoscintigraphic images of affected
      limbs in persons with both symptomatic and asymptomatic filarial infection, 36
      volunteers were recruited from a Wuchereria bancrofti-endemic area of Recife,
      Brazil, for a prospective, controlled analysis. Subjects were stratified after
      determination of serologic and clinical determinants of filarial infection
      status. Widespread lymphatic abnormalities were found in clinically asymptomatic
      microfilaremic persons, who had been assumed to have infection but not disease.
      All patients with clinical manifestations of lymphatic pathology and marked
      abnormalities. No correlation was found between clinical findings and actual
      lymphatic function as demonstrated by lymphoscintigraphy. The initial diagnosis
      of lymphatic filariasis, whether asymptomatic or symptomatic, is based on
      nonimaging laboratory criteria. After diagnosis, lymphoscintigraphy is a valuable
      tool for initial assessment of any lymphatic damage. Changes in strategies for
      therapeutic interventions in asymptomatic microfilaremic persons, who are not
      usually aggressively treated, may be warranted.

PMID- 7523539
TI  - Fascination with 2-5A-dependent RNase: a unique enzyme that functions in
      interferon action.
AB  - Interferon (IFN) treatment of cells results in the induction of 2-5A-synthetases,
      double-stranded RNA-activated enzymes that produce unusual 5'-phosphorylated
      2',5'-linked oligoadenylates known as 2-5A. 2.5A activates a unique IFN-induced
      endoribonuclease, the 2-5A-dependent RNase (RNase L), that is capable of
      degrading both viral and cellular RNA. The expression cloning of 2-5A-dependent
      RNase is leading to meaningful analysis of the physiological functions of the 2
      5A system. For example, expression in mouse cells of a dominant-negative mutant
      form of 2-5A-dependent RNase suppressed both the antiencephalomyocarditis virus
      and anticellular activities of IFN. Future investigations into this intriguing
      ribonuclease pathway promise to provide an intricate view into a molecular
      pathway of IFN action.

PMID- 7523541
TI  - Cytokeratins and tissue polypeptide antigen.
AB  - Cytokeratins (CKs), which are biochemically related to intermediate filaments
      (IFs), form an intracellular network of filaments that is believed to participate
      in maintaining the structural integrity of cells. Twenty individual polypeptides,
      divided into two groups, constitute the cytokeratin family. Each type of
      epithelial cell can be characterized by its content of cytokeratin polypeptides
      since the expression pattern varies with the type of epithelium. During
      transformation of normal epithelial cells into malignant cells, the cytokeratin
      patterns are usually maintained. This property has enabled the use of
      cytokerations as histological tumor markers, especially for tumors that are not
      easily classified. Cytokeratins 8, 18 and 19 are the most abundant cytokeratins
      in carcinomas. They are released into necrotic areas and can be found
      intratumorally and in blood, circulating as partially degraded complexes, and can
      as such be used as tumor markers. Cytokeratin deposits in tumors make these
      structures potential targets for radioimmunodetection and immunotherapy. The
      usefulness of tissue polypeptide antigen (TPA) as a serological tumor marker has
      been known for a long time. TPA is a molecular complex containing CK 8, 18 and 19
      and determinations of TPA in serum samples can be used in the follow-up of
      patients with many types of cancer.

PMID- 7523540
TI  - Distinction of mouse interferon-alpha subtypes by polymerase chain reaction
      utilizing consensus primers and type-specific oligonucleotide probes.
AB  - We have developed a novel method to study the subtype-specific expression of
      interferon-alpha (IFN-alpha) in the mouse system: we synthesized and used
      consensus oligonucleotide primers to allow simultaneous polymerase chain reaction
      (PCR) amplification of multiple murine IFN-alpha gene sequences. In addition, a
      set of subtype-specific oligomer probes were designed and used to distinguish
      between IFN-alpha genes that differ by only a few bases. The consensus primers,
      corresponding to two regions highly conserved among murine IFN-alpha subtypes,
      were used in reverse transcription and PCR amplification of total cellular RNA,
      isolated from IFN-gamma-treated murine L-929 cells, to yield a fragment of the
      anticipated approximately 520-bp size. Southern analysis of the amplified product
      using an internal consensus oligomer probe confirmed specific amplification of
      murine IFN-alpha gene(s). Subtype-specific oligonucleotide probes indicate that
      IFNs-alpha 1, -alpha 2, and -alpha 5 are present following IFN-gamma treatment,
      whereas IFN-alpha 4 remains virtually absent. Our results indicate that the
      expression of specific IFN-alpha subtypes may be subject to complex regulation,
      dependent upon inducing agents and cell types involved, and countless other
      factors. The procedure described here represents a novel method for studying the
      subtleties of the murine IFN-alpha mRNA expression.

PMID- 7523543
TI  - Cytokeratins in the histological diagnosis of malignant tumors.
AB  - Cytokeratins, which comprise a multigene family of 20 related polypeptides (CKs 1
      20), are constituents of the intermediate filaments of epithelial cells, in which
      they are expressed in various combinations depending on the epithelial type and
      the degree of differentiation. Of these, CK 19 (400 amino acids; 44.1
      kilodaltons) is an example of a widely distributed CK, being expressed in various
      epithelia, including many simple epithelia. In contrast, the recently identified
      CK 20 (424 amino acids; 48.6 kilodaltons) is essentially confined to
      gastrointestinal epithelia, the urothelium and Merkel cells. The differential
      expression of individual CKs in various types of carcinomas makes them useful
      markers for histopathological carcinoma subtyping, providing relevant information
      concerning the differentiation and origin of carcinomas, especially when tumors
      first present as metastases. The CKs that are of particular value for
      differential diagnosis include CK 20, as it is mainly expressed in carcinomas
      derived from CK 20-positive epithelia; it is also found in bile-tract, pancreatic
      and mucinous ovarian adenocarcinomas, being absent in most other carcinomas. In
      certain carcinoma types, the changes in the expression of individual CKs that may
      occur during tumor progression could be of prognostic relevance. It remains to be
      established whether the serological detection of fragments of not only widely
      distributed but also more restrictedly expressed CKs may provide useful
      serological tumor markers in the future.

PMID- 7523542
TI  - The correlation between serum levels of cytokeratin tumor markers does reflect
      their molecular characterization.

PMID- 7523544
TI  - The tumor markers TPA, TPS, TPACYK and CYFRA 21-1 react differently with the
      keratins 8, 18 and 19.
AB  - The commercially available tumor marker tests TPA, TPS, TPACYK and CYFRA 21-1
      react with simple epithelium keratins. From clinical studies it can be deduced
      that the pattern of keratin recognition must be different for each of these
      tests. We therefore studied the reactivity of the keratin fragment combinations
      K8/K18 and K8/K19 in the different tests and determined the reactivity of the
      corresponding soluble antibodies with purified keratin 8, 18 and 19 in
      immunoblots. TPS and CYFRA 21-1 were found to distinguish clearly between the
      keratin fragment combinations K8/K18 (TPS) and K8/K19 (CYFRA 21-1). TPA and
      TPACYK reacted with both combinations, however, with different intensities. On
      immunoblots the CYFRA 21-1 antibodies reacted exclusively with K19, whereas the
      antibodies of the other assays reacted with at least 2 of the keratins
      investigated.

PMID- 7523545
TI  - Lung cancer-associated keratin 19 fragments: development and biochemical
      characterisation of the new serum assay Enzymun-Test CYFRA 21-1.
AB  - From a panel of 4 murine monoclonal antibodies directed against keratin 19
      various antibody combinations were evaluated in solid-phase enzyme-linked
      sandwich immunoassays for detection of soluble keratin 19 fragments in patient
      sera. One of these antibody combinations, comprised of the monoclonal antibodies
      Ks 19.1 and BM 19.21, was selected for further development to a routine test
      (Enzymun-Test CYFRA 21-1) because of its high diagnostic sensitivity and
      specificity for non-small cell lung carcinoma (NSCLC). Both antibodies are
      specific for keratin 19, no reactivity could be observed with cytokeratin 8 or
      18. The epitopes of the two antibodies were determined to be within helix 2B of
      the rod romain. The epitope sequences lie within the sequence 311-335 for the
      catcher antibody Ks 19.1 and 346-367 for the detector antibody BM 19.21. These
      sequences are unique, as could be confirmed from sequence databases. The standard
      material for the assay was prepared from a cytoskeleton fraction of cultivated
      MCF-7 cells. Subsequent digestion of this fraction with chymotrypsin yielded a
      soluble and stable standard material. Both the standard material and the serum
      analyte appeared as oligomers when analysed on gel chromatography: the serum
      analyte appeared exclusively at a M(r) of 100 +/- 10 kD, whereas the standard
      material eluted in fractions corresponding to 100 +/- 10 kD and 450 kD. Due to
      the precise definition of the antigen and the localisation of the antibody
      binding sequences, Enzymun-Test CYFRA 21-1 is one of the best characterised tumor
      markers so far.

PMID- 7523546
TI  - Comparison of CYFRA 21-1, TPA and TPS in lung cancer, urinary bladder cancer and
      benign diseases.
AB  - Recently CYFRA 21-1, a new tumor marker measuring a fragment of cytokeratin 19,
      was introduced and proved to be suitable for therapy monitoring and follow-up of
      non-small cell lung carcinomas (NSCLC), in particular squamous cell carcinomas.
      Besides CYFRA 21-1 there are two other tumor markers, tissue polypeptide antigen
      (TPA) and tissue polypeptide-specific antigen (TPS), which also measure various
      cytokeratins in serum. In a retrospective study we investigated the clinical
      significance of these three cytokeratin markers in lung cancer and in carcinoma
      of the urinary bladder. For this purpose we investigated the sera of 50 healthy
      persons, 273 patients with various benign diseases, 218 patients with
      histologically proven lung cancer and 88 patients with carcinoma of the urinary
      bladder. In a first step the specificity was established for the different
      reference groups and the cutoff values were fixed at a specificity of 95%. In
      lung cancer the single and combined sensitivities were calculated versus benign
      lung diseases (n = 58) as reference group. With single determinations CYFRA 21-1
      proved to have the highest sensitivity in lung cancer in general (61%), in non
      small cell lung carcinomas (64%), in squamous cell carcinomas (79%), in
      adenocarcinomas (54%) and in large cell carcinomas (65%). In small cell lung
      carcinomas (SCLC) NSE was confirmed to be the marker of choice (55%). With
      combined determinations a clear increase in sensitivity could only be reached in
      large cell carcinomas (CYFRA 21-1 + TPA: 77%) and in small cell carcinomas (CYFRA
      21-1 + NSE: 62%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523547
TI  - Evaluation of cytokeratin 19 serum fragments (CYFRA 21-1) in patients with lung
      cancer: results of a multicenter trial.
AB  - Recently, a new immunometric assay (Cyfra 21-1) was developed to measure serum
      concentrations of a soluble fragment of cytokeratin subunit 19. With this method,
      supplied by Boehringer Mannheim (EIA Test Cyfra 21-1), an Italian multicenter
      trial was performed in patients with lung cancer. Cyfra 21-1 serum levels were
      determined in 568 normal subjects (blood donors), 607 patients with non-malignant
      diseases (491 respiratory diseases) and 730 patients with malignancies. In the
      latter group 584 had lung cancer. All these 584 patients had pathologically
      confirmed disease; 314 were epidermoid tumors, 166 adenocarcinomas, 88 small cell
      cancers and 16 large cell cancers. In the 568 healthy blood donors the mean Cyfra
      21-1 value was 0.91 ng/ml (SD 0.47 ng/ml; range 0.05-2.90 ng/ml). A threshold of
      1.9 ng/ml was chosen as the upper limit of normality. High levels of Cyfra 21-1
      were observed in patients with chronic hepatitis (positivity rate: 17/51-33.3%)
      and with pancreatitis (positivity rate 5/16-31.3%). In 114 out of 491 (23.2%)
      patients with respiratory diseases Cyfra 21-1 showed values greater than 1.9
      ng/ml. The overall sensitivity (all stages) of Cyfra 21-1 in lung cancer was
      65.6% (383/584). When the histology was considered the highest positivity rates
      were found in patients with squamous cell tumors (226/314; 72%) followed by
      adenocarcinomas (105/166; 63%). In patients with SCLC the global sensitivity was
      52.3% (46/88). Higher sensitivity of Cyfra 21-1 was observed from stage I to
      stage IV (53.9% vs 85.7%; Chi square: p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523548
TI  - CYFRA 21-1 in lung cancer: comparison with CEA, CA 125, SCC and NSE serum levels.
AB  - CYFRA 21-1, CEA, CA 125, SCC and NSE serum levels were determined in 50 healthy
      subjects and in 189 patients with primary lung cancer (101 with locoregional
      disease, 68 with recurrence and 20 patients with no evidence of residual disease
      (NED). Abnormal CYFRA 21-1 serum levels were found in 53.6% (90/168) of the
      patients with active cancer. Neither healthy subjects nor NED patients had
      abnormal serum levels. CYFR alpha 21-1 serum concentrations were significantly
      higher in patients with active cancer than in healthy subjects or in NED patients
      (p < 0.0001). CYFRA 21-1 sensitivity was related to tumor histology with abnormal
      levels in 64.7% of patients with NSCLC and in 30% of patients with SCLC (P <
      0.0001). In NSCLC, serum CYFRA 21-1 concentrations were also related to
      histological type, the highest values being found in squamous cell carcinomas and
      LCLC and the lowest in adenocarcinomas (p < 0.04). There was also a clear
      relationship between CYFRA 21-1 and tumor extension, with significantly higher
      values in patients with metastases than in those without metastases (p < 0.0001).
      Abnormal CEA values were found in 49.1%, CA 125 in 39%, SCC in 27.8% and NSE in
      21.3% of the patients with active cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523550
TI  - The genetic basis of autoimmune disease in MRL-lpr/lpr mice.

PMID- 7523551
TI  - Tight-skin mouse an experimental model for scleroderma.

PMID- 7523549
TI  - A new CCK-B/gastrin receptor antagonist acts as an agonist on the rat pancreas.
AB  - The new CCK-B/gastrin receptor antagonist PD 136450 is of potential value in
      treating neurologic and psychiatric disorders. We investigated possible side
      effects on the rat pancreas using acute and chronic administration schedules. In
      chronic experiments, four groups of rats were given either PD 136450, the proton
      pump inhibitor BY 308 (in order to induce hypergastrinemia), a combination of
      both, or control solutions over 14 d. Pancreatic growth, DNA, and protein content
      were significantly increased in rats given PD 136450 irrespective of circulating
      gastrin levels. Furthermore, an anticoordinate shift in pancreatic enzyme content
      in favor of trypsin and chymotrypsin at the expense of amylase and lipase was
      observed. Plasma CCK levels remained unchanged in this group making a role of
      circulating hormone unlikely. In order to investigate a possible direct agonist
      effect of the CCK-B/gastrin receptor antagonist, we studied amylase release from
      isolated rat pancreatic acini in response to PD 136450 and sulfated CCK8 alone
      and in combination with the specific CCK-A receptor antagonist MK 329. Increasing
      concentrations of PD 136450 caused a monophasic dose-response curve in contrast
      to the well-known biphasic amylase release in response to CCK8. Addition of
      increasing doses of PD 136450 to a concentration of CCK causing maximal
      stimulation of amylase release (0.1 nM) further enhanced amylase release from
      pancreatic acini. The specific CCK-A receptor antagonist MK 329 dose-dependently
      inhibited CCK8- and PD 136450-induced amylase release. In conclusion, the new CCK
      B/gastrin receptor antagonist PD 136450 exhibited profound agonist actions on the
      rat pancreas mediated via CCK-A receptors.

PMID- 7523552
TI  - Bacillary angiomatosis: investigation of the unusual interactions between
      Rochalimaea bacilli and endothelial cells.

PMID- 7523553
TI  - Rochalimaea species stimulate human endothelial cell proliferation and migration
      in vitro.
AB  - Rochalimaea henselae and R. quintana are associated clinically with proliferative
      neovascular lesions. The effect of Rochalimaea species on human umbilical vein
      endothelial cell (HUVEC) proliferation and migration was evaluated in vitro.
      Cocultivation of Rochalimaea organisms with HUVECs resulted in enhanced HUVEC
      proliferation. Fibroblast proliferation was unaffected by R. henselae. HUVECs
      were also stimulated to migrate by Rochalimaea. When R. henselae organisms were
      disrupted and subjected to centrifugation, the ability to enhance HUVEC
      proliferation and migration was localized to the particulate, noncytosolic
      fraction. Trypsin treatment of this fraction diminished its stimulatory activity.
      These data suggest that the neovascular manifestations of infection with
      Rochalimaea are likely caused by the production of an angiogenic factor by these
      bacteria.

PMID- 7523555
TI  - Selective alpha IIb beta 3 receptor blockage with peptide TP9201 prevents
      platelet uptake on Dacron vascular grafts without significant effect on bleeding
      time.
AB  - Synthetic vascular prostheses lack the uniquely low thrombogenicity provided by
      the endothelial cell lining of autogenous saphenous vein or artery grafts. The
      thrombogenic nature of the synthetic graft surface becomes a major determinant of
      early prosthetic graft patency. We demonstrate in a baboon ex vivo synthetic
      graft model that modification of the host's platelet interaction with the graft
      surface results in inhibition of platelet thrombus formation and thereby, a
      possible enhancement of early prosthetic graft patency. This was achieved by
      selective blockage of the platelet alpha IIb beta 3 receptor by the arginine
      glycine-aspartic acid-containing synthetic peptide TP9201. Platelet thrombus
      formation on a Dacron graft indicated by accumulation of indium III-oxine-labeled
      autologous platelets was measured by gamma camera imaging. After 60 minutes of
      circulation, TP9201 at a bolus of 125 micrograms/kg; infusion of 3
      micrograms/kg/min, bolus of 190 micrograms/kg; infusion of 5 micrograms/kg/min,
      bolus of 250 micrograms/kg; infusion of 6 micrograms/kg/min, and bolus of 500
      micrograms/kg; infusion of 12 micrograms/kg/min decreased platelet uptake on the
      graft to 50%, 40%, 30%, and 10% of control uptake, respectively. Forelimb
      template bleeding times were not found to be significantly prolonged at doses
      that effectively inhibit ex vivo platelet aggregation. As a result of drug
      treatment, no changes in hemodynamic parameters or hematologic profile, including
      platelet number and clotting time, were observed. We demonstrate here that the
      arginine-glycine-aspartic acid-containing peptide TP9201, which competitively
      inhibits the alpha IIb beta 3 integrin-fibrinogen interaction, significantly
      decreased the accumulation of platelets on a Dacron vascular graft. Molecules
      like peptide TP9201, because of its unique activity profile, may represent a
      superior approach to the control of platelet accumulation on thrombogenic
      surfaces.

PMID- 7523556
TI  - Cytokine networks in solid human tumors: regulation of angiogenesis.
AB  - The isolation, purification, and molecular cloning of an increasing number of
      cytokines and their receptors have allowed major advances in our understanding of
      the relevance of these proteins to the pathobiology and treatment of such human
      diseases as neoplasia. Cytokines produced by the multiple cell types present
      within the microenvironment of solid tumors from a complex, dynamic network, in
      which they have overlapping properties, induce other cytokines and alter the
      expression of soluble and cell surface-bound cytokine receptors. A broad number
      of such intratumoral cytokines have multiple effects on tumor progression. These
      include direct and indirect effects both on tumor cell growth and metastatic
      behaviors and on such cells in the stromal compartment as fibroblasts,
      infiltrating immune cells, and endothelial cells in the microvasculature. Here,
      we review the sites of production and multifaceted role of several key cytokines
      in the stimulation of a new blood supply within growing neoplasms. The clinical
      implications and new therapeutic targets suggested by this rapidly emerging
      picture of the cellular and molecular mechanisms subserving tumor angiogenesis
      are also discussed.

PMID- 7523554
TI  - Albumin binding surfaces for biomaterials.
AB  - The surfaces of medical devices may promote both coagulation and infections
      caused by adherent microorganisms. In the case of polymeric elastomers, these
      iatrogenic effects are likely intermediated by absorbed host proteins that
      spontaneously bind to the device surface, promoting both bacterial adherence and
      thrombotic events. We earlier attempted to produce biomaterial surfaces that
      would selectively bind host albumin because albumin-coated surfaces were known to
      diminish both coagulation and bacterial adherence. To this end, an albumin
      binding high molecular weight dextran:Cibacron blue adduct was bulk incorporated
      into polyetherurethane (Keogh et al., J Biomed Mater Res 1992;26:441). The
      modified material bound albumin selectively and reversibly and showed evidence of
      enhanced biocompatibility. However, approximately 30% of the surface of this
      material was evidently unmodified and still capable of exerting the above adverse
      effects. In the present work, we have covalently surface-modified
      polyetherurethane with sequential additions of acrylamide, amino
      propylmethacrylamide, dextran, and Cibacron blue. This derivatized polyurethane
      preferentially and reversibly binds albumin, even from complex mixtures of
      proteins such as plasma. Furthermore, this material inhibits the clotting of
      nonanticoagulated whole human blood (for > 16 hours at room temperature), perhaps
      by virtue of binding and activation of antithrombin III by the sulfonic acid
      residues on the surface-immobilized Cibacron blue. Finally, such surfaces,
      especially when bearing bound albumin, diminish the adherence of Staphylococcus
      epidermidis, a pathogen frequently associated with device-centered infections. We
      conclude that similar albumin-affinity surfaces may hold promise for the
      development of more biocompatible materials for implantation and blood contact
      applications.

PMID- 7523557
TI  - Coengagement of CD2 with LFA-1 or VLA-4 by bispecific ligand fusion proteins
      primes T cells to respond more effectively to T cell receptor-dependent signals.
AB  - To examine the effects of ligand engagement and accessory molecule juxtaposition
      on T cell receptor (TCR) signaling, we prepared LFA-3/ICAM-1 Rg and LFA-3/VCAM-1
      Rg bispecific immunoglobulin fusion proteins (Rg, recombinant globulin). These
      novel fusion proteins allowed us to examine the effects of ligand driven co
      engagement of T cell proteins CD2 and LFA-1 or CD2 and VLA-4 on TCR-dependent
      mobilization of intracellular Ca2+. We observed that preincubation of resting T
      cells with LFA-3/ICAM-1 Rg or LFA-3/VCAM-1 Rg fusion proteins resulted in
      significantly enhanced mobilization of intracellular Ca2+ following TCR-accessory
      molecule cross-linking relative to T cells preincubated with each of the
      monospecific Rgs alone or with combinations of the monospecific Rg fusion
      proteins. In addition, such coengagement stimulated TCR-dependent activation and
      tyrosine phosphorylation of phospholipase C gamma 1 (PLC gamma 1). These results
      suggest that when T cells interact with antigen presenting cells the engagement
      of multiple cell adhesion molecules such as CD2, LFA-1, and VLA-4 primes the T
      cell to respond more effectively to signals delivered through the TCR.

PMID- 7523558
TI  - Production of nitric oxide by differentiated LSTRA cells is associated with
      expression of macrophage-inducible nitric oxide synthase.
AB  - LSTRA is a mouse lymphoma cell line overexpressing the src-related oncogene
      product and T cell marker p56lck. We have discovered that LSTRA cells, like HL60
      and U937 promyelocytic leukemia cells, can be induced to differentiate toward
      macrophages by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) or
      granulocytes by the cyclic nucleotide analogue dibutyryl cAMP (dbcAMP). One
      property of mature macrophages and granulocytes is the ability to produce nitric
      oxide, a highly reactive free radical that is important in non-specific host
      defense. Nitric oxide production by mature macrophages is stimulated by
      inflammatory mediators via an inducible form of the enzyme, nitric oxide
      synthase. We report that LSTRA cells acquire the ability to produce nitric oxide
      following differentiation induced by TPA and, to a lesser extent, by dbcAMP.
      Nitric oxide production by the cells is dependent on L-arginine and blocked by
      several inhibitors of nitric oxide synthase, including N-monomethyl-L-arginine, L
      canavanine, L-arginine benzyl ester, and L-arginine methyl ester. In macrophage
      differentiated LSTRA cells, the inflammatory cytokine interferon-gamma was found
      to be a potent inducer of nitric oxide production. This was correlated with a
      marked increase in nitric oxide synthase activity in the cells that was due to
      interferon-gamma-induced expression of the macrophage-inducible form of nitric
      oxide synthase protein as well as mRNA. Differentiated LSTRA cells also expressed
      increased amounts of a constitutive form of nitric oxide synthase that was also
      present in undifferentiated cells. Taken together with previous findings, these
      results support the model that LSTRA cells have the capacity to differentiate
      toward mature macrophages.

PMID- 7523559
TI  - L-selectin mediates downregulation of neutrophil TNF receptors.
AB  - Tumor necrosis factor (TNF) is a potent activator of neutrophil granulocytes,
      which acts via two cell-surface receptors: the p55-TNF receptor (TNF-R55) and the
      p75-TNF receptor (TNF-R75). Proteolytic cleavage of the extracellular region of
      the receptors results in formation of soluble TNF-binding proteins, TNF-R55-BP
      and TNF-R75-BP. We recently reported that adherence alone, without any further
      stimuli, causes release of both TNF-R55-BP and TNF-R75-BP and that both leukocyte
      integrin-dependent and non-integrin-dependent adherence mechanisms can modulate
      TNF receptor expression. In the present work we show that crosslinking of a mAb
      to the adhesion protein L-selectin (TQ1) on the surface of neutrophils results in
      downregulation of TNF-receptor binding capacity. Furthermore, when the
      fluctuations of cytosolic free calcium found in adherent neutrophils were blocked
      with the cell-permeable calcium chelator BAPTA, adherence-induced release of TNF
      R55-BP was inhibited. We have shown that adherence, via mechanisms involving two
      adhesion proteins, L-selectin and the CD11/CD18 leukocyte integrins, and
      fluctuations of cytosolic free calcium, can result in downregulation of
      neutrophil TNF-receptors.

PMID- 7523560
TI  - Detection of keratinocyte growth factor (KGF) transcripts from normal human and
      archival canine benign prostatic hyperplastic tissues.
AB  - This study examined the expression of keratinocyte growth factor (KGF) gene in
      human and canine prostatic tissues. KGF transcript was detected in normal human
      prostatic tissues by reverse transcription and polymerase chain reactions (RT
      PCR). PCR-generated human KGF complementary DNA (cDNA) clone was confirmed by
      restriction enzyme digestion analysis and partial DNA sequencing. Expression of
      KGF in archival canine benign prostatic hyperplastic tissues was also examined.
      In a pilot experiment, RNAs isolated from formalin-fixed (FF) and formalin-fixed
      and paraffin-embedded (FFPE) canine prostatic tissues were shown to be of
      sufficient quality to permit amplification of KGF mRNA by RT-PCR. The transcript
      of a housekeeping gene, glucose-6-phosphate dehydrogenase (G6PD), was detected by
      RT-PCR indicating the quality of RNAs to be more than adequate for RNA expression
      analysis. Later, total RNA from two archival canine FF prostate tissue types,
      benign prostatic hyperplasis and mild glandular hyperplasia, were used to amplify
      canine KGF transcripts. Southern hybridization analysis using rat and human KGF
      cDNAs as probes confirmed the fidelity of the amplified PCR product and it was
      indeed canine KGF.

PMID- 7523561
TI  - Pancreatic hormones differentially regulate insulin-like growth factor (IGF)-I
      and IGF-binding protein production by primary rat hepatocytes.
AB  - We investigated the influence of and interactions among pancreatic hormones on
      the secretion of insulin-like growth factor-I (IGF-I) and IGF-binding proteins
      (IG-FBPs) by treating primary hepatocytes from young male Long-Evans rats with
      insulin or glucagon in combination with rat GH (rGH). The concentration of IGF-I
      secreted into the medium was estimated by radioimmunoassay after formic acid
      acetone cryoextraction, and secreted IGFBPs were analysed by Western ligand blot
      and immunoblot; accumulation of IGF-I mRNA was analysed by Northern blot. Both
      insulin (0.1-100 nmol/l) and rGH (0.5, 5 and 50 pmol/l) produced a dose-dependent
      stimulation of IGF-I secretion over a 24-h incubation period. In contrast,
      glucagon (0.1-100 nmol/l) inhibited IGF-I production in a dose-related manner.
      Glucagon (10 nmol/l) also inhibited IGF-I secretion stimulated by rGH (5 pmol/l)
      and insulin (10 nmol/l). Northern blot analysis of total RNA isolated from rat
      hepatocytes revealed that rGH (5 pmol/l) elevated IGF-I mRNA levels, glucagon (10
      nmol/l) alone had no effect on this parameter, but glucagon significantly reduced
      IGF-I transcript accumulation in response to rGH. IGFBPs secreted by rat
      hepatocytes run in two molecular weight ranges on SDS-PAGE: approximately 25 kDa
      (IGFBP-4) and approximately 29-31 kDa (IGFBP-1 and -2); the predominant
      hormonally regulated IGFBP was identified as IGFBP-1. Insulin produced a dose
      dependent inhibition of production of IGFBP-1, while glucagon was stimulatory;
      when given together at an equivalent concentration (1 nmol/l), the effects of
      insulin were dominant to glucagon on IGFBP-1. These observations provide support
      for significant opposite roles for the pancreatic hormones, insulin and glucagon,
      in the regulation of liver IGF-I and IGFBP-1 production. As the production of
      pancreatic hormones is influenced by nutritional status, these polypeptides may
      mediate the effects of changing nutritional state on the hormonal control of
      protein anabolism and glucose homeostasis by directly influencing the circulating
      level of liver-derived IGF-I and its binding proteins.

PMID- 7523563
TI  - Levels of insulin-like growth factor-binding protein-2 and insulin-like growth
      factor-II in maternal serum, amniotic fluid and extraembryonic coelomic fluid at
      9-20 weeks of pregnancy.
AB  - Insulin-like growth factor-II (IGF-II) and IGF-binding protein-2 (IGFBP-2) were
      measured in amniotic fluid, extraembryonic fluid and maternal serum from 20 women
      with apparently normal first trimester pregnancies prior to termination. A
      further 111 specimens of amniotic fluid were collected from women at 10-20 weeks
      of pregnancy. Levels of IGFBP-2 were similar in coelomic fluid and maternal
      serum. Levels in amniotic fluid were lower than those in serum and coelomic fluid
      (Mann-Whitney test; P = 0.0002 and P < 0.0001 respectively). The levels of IGF-II
      were much higher in maternal serum than in coelomic fluid, and higher in the
      latter than in amniotic fluid (Mann-Whitney test; P < 0.0001 for both
      situations). The levels of IGFBP-2 were relatively low at 10-11 weeks (medians
      19.8 and 61.1 micrograms/l) but thereafter increased to 20 weeks (median 1400
      micrograms/l). The levels of IGF-II showed a similar pattern. The findings
      suggest that the role of IGF-II and IGFBP-2 in the regulation of growth or
      differentiation of the fetus or of its surrounding membranes may change with
      advancing pregnancy.

PMID- 7523564
TI  - Gadolinium is a powerful blocker of the activation of nematocytes of Pelagia
      noctiluca.
AB  - The activation properties of in situ nematocytes of Pelagia noctiluca (Scyphozoa)
      were investigated by physical contact with a gelatin probe that, besides
      stimulating the nematocyte battery, retains the discharged nematocysts, thereby
      allowing a quantitative evaluation of the response. In oral arms previously
      treated with 2 mmol l-1 La3+ the discharge was inhibited. This result confirms
      the Ca(2+)-dependence of nematocyte activation. A similar inhibitory effect was
      induced by treatment with 20 mumol l-1 Gd3+, a powerful blocker of
      mechanosensitive ion channels. It is therefore proposed that Ca(2+)-permeable
      mechanosensitive channels are involved in the activation of nematocytes. 50 mumol
      l-1 Gd3+ added to the gelatin probe was effective in otherwise untreated oral
      arms. This result suggests that Gd3+ could be useful in preventing stings from
      harmful Cnidaria.

PMID- 7523565
TI  - Pathophysiology of fibrinolysis.

PMID- 7523562
TI  - The effects of recombinant human insulin-like growth factor-I (IGF-I)
      administration on the levels of IGF-I, IGF-II and IGF-binding proteins in
      adolescents with insulin-dependent diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus (IDDM) during puberty is associated with a
      reduction in circulating concentrations of insulin-like growth factor-I (IGF-I)
      and low IGF bioactivity. Altered levels of the IGF-binding proteins (IGFBPs),
      including low IGFBP-3 and elevated IGFBP-1, have also been described. These
      abnormalities have been linked to poor growth and deteriorating blood glucose
      control. We have therefore examined the effects of recombinant human IGF-I (rhIGF
      I) administration on the levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3 and IGF
      bioactivity in a group of 9 late-pubertal adolescents with IDDM. This was a
      double-blind placebo controlled study with each individual admitted on two
      occasions when either rhIGF-I (40 micrograms/kg) or placebo was administered by
      subcutaneous injection in the thigh at 1800 h. Blood samples were then taken for
      the subsequent 22 h. The half-life of administered rhIGF-I (12.1-22.2 h) was
      similar to that previously described in normal subjects. There was a small
      increase in IGFBP-3 concentrations overnight following rhIGF-I administration
      when compared to placebo, whereas the levels of IGF-II decreased. Under strict
      euglycaemic conditions, the relationship between insulin and IGFBP-I did not
      appear to be affected by rhIGF-I administration although the levels of IGFBP-1
      tended to be higher overnight. IGF bioactivity was low during the placebo study,
      and although within the normal adult range following administration of IGF-I, was
      still relatively low for adolescents in late puberty.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7523566
TI  - The essence of epitopes.

PMID- 7523567
TI  - Murine B cell proliferation and protection from apoptosis with an antibody
      against a 105-kD molecule: unresponsiveness of X-linked immunodeficient B cells.
AB  - We established a novel monoclonal antibody, RP/14, that can protect B cells from
      apoptosis induced by irradiation or dexamethasone. A molecule recognized by RP/14
      (the RP antigen) was expressed on B cells with B220bright, IgMdull, and
      IgDbright. Immunoprecipitation experiments revealed that RP/14 recognized a
      monomeric protein with an approximate molecular mass of 105 kD. Stimulation of B
      cells with RP/14 for 48 h induced B cell proliferation and blastogenesis. In
      contrast to B cells of wild-type mice, X-linked immunodeficient (XID) B cells did
      not proliferate upon stimulation with RP/14, although the RP antigen was
      expressed to the same extent as that of wild-type B cells. These results suggest
      that the RP antigen-mediated signaling pathway is important for rescuing B cells
      from apoptosis and is deficient in XID B cells.

PMID- 7523569
TI  - Activation of human dendritic cells through CD40 cross-linking.
AB  - Dendritic cells, the professional antigen-presenting cells (APC) involved in T
      cell priming, express CD40, a molecule which triggering plays a key role in B
      cell growth and differentiation as well as monocyte activation. Herein we
      demonstrate that dendritic Langerhans cells (D-Lc) generated by culturing cord
      blood CD34+ progenitor cells with granulocyte/macrophage colony-stimulating and
      tumor necrosis factor alpha (TNF-alpha) express functional CD40 at a density
      higher than that found on B cells. Culturing D-Lc on CD40-ligand (CD40L)
      transfected L cells allowed D-Lc survival as 50 +/- 15% of seeded cells were
      recovered after 4 d while only 5% survived over control L cells. CD40 activation
      induced important morphological changes with a reduction of cytoplasmic content
      and a remarkable increase of dendrite development as well as an altered
      phenotype. In particular, CD40 triggering induced maintenance of high levels of
      major histocompatibility complex class II antigens and upregulation of accessory
      molecules such as CD58, CD80 (B7-1) and CD86 (B7-2). CD40 engagement also seems
      to turn on D-Lc maturation as illustrated by upregulation of CD25, a molecule
      usually expressed on interdigitating dendritic cells of secondary lymphoid
      organs. Finally, CD40 activated D-Lc secreted a limited set of cytokines (TNF
      alpha, IL-8, and macrophage inflammatory protein 1 alpha [MIP-1 alpha]) whereas a
      similar activation induced elutriated monocytes to secrete IL-1 alpha, IL-1 beta,
      IL-6, IL-8, IL-10, TNF-alpha, and MIP-1 alpha. As D-Lc activated T cells
      upregulated CD40L, it is likely that CD40 activation of D-Lc observed herein with
      a fibroblast cell line stably expressing CD40L, mimics physiological interactions
      between dendritic cells and T cells.

PMID- 7523568
TI  - Heterogeneity of single cell cytokine gene expression in clonal T cell
      populations.
AB  - T helper type 0 (Th0), Th1, and Th2 CD4+ T cell clones derived from a T cell
      receptor alpha/beta (TCR-alpha/beta) transgenic mouse were activated by antigen
      presented on "artificial" antigen-presenting cells that expressed or lacked the
      costimulatory molecule B7-1, and were analyzed for single cell cytokine mRNA
      expression by in situ hybridization. There was significant heterogeneity in the
      frequency of T cells that expressed individual cytokine mRNAs within each clonal
      population, suggesting that transcriptional control of each of the cytokine genes
      was not coordinate within an individual cell. The majority of antigen-stimulated
      Th1 cells expressed mRNA for interferon gamma (IFN-gamma), but far fewer cells in
      the same population expressed interleukin 2 (IL-2). Similarly, the frequency of
      IL-4-expressing cells was greater than that of IL-5- or IL-10-expressing cells in
      the same Th2 population, but the difference in expression frequencies was more
      variable between clones. The expression frequencies of each of the cytokines was
      quite heterogeneous in the antigen-activated Th0 population. The principal effect
      of increased antigen on the activation of individual cytokine genes in each of
      the clonal populations was to increase recruitment of mRNA-positive cells, with
      little or no effect on the level of cytokine mRNA expression in individual
      positive cells. The effects of B7 costimulation were variable depending on the
      cytokine gene analyzed. B7 costimulation markedly increased the frequency and the
      level of IL-2 mRNA expression in individual positive cells in the Th1 and Th0
      populations, with less effect on the recruitment and single cell expression level
      of IFN-gamma. IL-4 frequencies were modestly increased by B7 costimulation of the
      Th2 clones, but there was no detectable increase in single cell IL-4 expression
      level. The observed patterns of cytokine mRNA expression favor a model of T cell
      activation in which all-or-none, rather than graded, responses of cytokine genes
      are dominant.

PMID- 7523570
TI  - Naturally processed viral peptides recognized by cytotoxic T lymphocytes on cells
      chronically infected by human immunodeficiency virus type 1.
AB  - We have established long-term cultures of several cell lines stably and uniformly
      expressing human immunodeficiency virus type 1 (HIV-1) in order to (a) identify
      naturally processed HIV-1 peptides recognized by cytotoxic T lymphocytes (CTL)
      from HIV-1-seropositive individuals and (b) consider the hypothesis that
      naturally occurring epitope densities on HIV-infected cells may limit their lysis
      by CTL. Each of two A2-restricted CD8+ CTL specific for HIV-1 gag or reverse
      transcriptase (RT) recognized a single naturally processed HIV-1 peptide in
      trifluoroacetic acid (TFA) extracts of infected cells: gag 77-85 (SLYNTVATL) or
      RT 476-484 (ILKEPVHGV). Both processed peptides match the synthetic peptides that
      are optimally active in cytotoxicity assays and have the consensus motif
      described for A2-associated peptides. Their abundances were approximately 400 and
      approximately 12 molecules per infected Jurkat-A2 cell, respectively. Other
      synthetic HIV-1 peptides active at subnanomolar concentrations were not present
      in infected cells. Except for the antigen processing mutant line T2, HIV-infected
      HLA-A2+ cell lines were specifically lysed by both A2-restricted CTL, although
      infected Jurkat-A2 cells were lysed more poorly by RT-specific CTL than by gag
      specific CTL, suggesting that low cell surface density of a natural peptide may
      limit the effectiveness of some HIV-specific CTL despite their vigorous activity
      against synthetic peptide-treated target cells.

PMID- 7523571
TI  - Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells
      via components of the IL-2 receptor.
AB  - Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and
      expressed. Whereas it has no sequence homology with IL-2, IL-15 interacts with
      components of the IL-2 receptor (IL-2R). In the present study we performed a
      functional analysis of recombinant IL-15 on phenotypically and functionally
      distinct populations of highly purified human natural killer (NK) cells. The
      CD56bright subset of human NK cells constitutively expresses the high affinity IL
      2R and exhibits a brisk proliferative response after the binding of picomolar
      amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep
      dose-response curve that was distinct from the dose-response curve for IL-2. The
      proliferative effects of IL-15 could be abrogated by anti-IL-2R beta (p75), but
      not by anti-IL-2R alpha (p55). The proliferative effects of IL-2 on CD56bright NK
      cells could be inhibited by both antibodies. CD56dim NK cells express the
      intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation
      of CD56dim NK cells by IL-15 was similar to that of IL-2 as measured by enhanced
      NK cytotoxic activity, antibody-dependent cellular cytotoxicity, and NK cell
      production of interferon gamma, tumor necrosis factor alpha, and
      granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic
      activity could be completely blocked by anti-IL-2R beta monoclonal antibody. The
      binding of radiolabeled IL-2 and IL-15 to CD56dim NK cells was inhibited in the
      presence of anti-IL-2R beta. Scatchard analysis of radiolabeled IL-15 and IL-2
      binding to NK-enriched human lymphocytes revealed the presence of high and
      intermediate affinity receptors for both ligands. IL-15 is a ligand that
      activates human NK cells through components of the IL-2R in a pattern that is
      similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by
      activated monocytes/macrophages. The discovery of IL-15 may increase our
      understanding of how monocytes/macrophages participate in the regulation of NK
      cell function.

PMID- 7523572
TI  - Determinant selection of major histocompatibility complex class I-restricted
      antigenic peptides is explained by class I-peptide affinity and is strongly
      influenced by nondominant anchor residues.
AB  - The contribution of major histocompatibility complex (MHC) class I-peptide
      affinity to immunodominance of particular peptide antigens (Ags) in the class I
      restricted cytotoxic T lymphocyte (CTL) response is not clearly established.
      Therefore, we have compared the H-2Kb-restricted binding and presentation of the
      immunodominant ovalbumin (OVA)257-264 (SIINFEKL) determinant to that of a
      subdominant OVA determinant OVA55-62 (KVVRFDKL). Immunodominance of OVA257-264
      was not attributable to the specific T cell repertoire but correlated instead
      with more efficient Ag presentation. This enhanced Ag presentation could be
      accounted for by the higher affinity of Kb/OVA257-264 compared with Kb/OVA55-62
      despite the presence of a conserved Kb-binding motif in both peptides. Kinetic
      binding studies using purified soluble H-2Kb molecules (Kbs) and biosensor
      techniques indicated that the Kon for association of OVA257-264-C6 and Kbs at 25
      degrees C was integral of 10-fold faster (5.9 x 10(3) M-1 s-1 versus 6.5 x 10(2)
      M-1 s-1), and the Koff approximately twofold slower (9.1 x 10(-6) s-1 versus 1.6
      x 10(-5) s-1), than the rate constants for interaction of OVA55-62-C6 and Kbs.
      The association of these peptides with Kb was significantly influenced by
      multiple residues at presumed nonanchor sites within the peptide sequence. The
      contribution of each peptide residue to Kb-binding was dependent upon the
      sequence context and the summed contributions were not additive. Thus the
      affinity of MHC class I-peptide binding is a critical factor controlling
      presentation of peptide Ag and immunodominance in the class I-restricted CTL
      response.

PMID- 7523574
TI  - The endoplasmic reticular heat shock protein gp96 is transcriptionally
      upregulated in interferon-treated cells.
AB  - A cDNA clone complementary to an interferon (IFN)-induced mRNA approximately 3 kb
      in length was identified and sequenced revealing homology with the endoplasmic
      reticular heat shock protein/ATPase gp96. Both IFN-alpha and -gamma
      transcriptionally upregulate expression of this gene. gp96 transcripts, protein,
      and ATPase activity are shown to be enhanced as a result of IFN treatment in two
      human cell lines and this effect requires de novo protein synthesis. gp96
      molecules have recently been implicated in the presentation of endogenous
      antigens. A number of the key elements in this pathway, the transporter proteins,
      the major histocompatibility complex (MHC)-linked units of the proteasomes and
      the MHC class I molecules are known to be IFN inducible. Our results show that
      yet another molecule suggested to play an accessory role in the endogenous
      presentation pathway is IFN inducible. Further, our studies represent the first
      demonstration of modulation of expression of a heat shock protein by a cytokine
      and identify a new enzymatic activity upregulated in IFN-treated cells.

PMID- 7523573
TI  - Apoptotic signaling through CD95 (Fas/Apo-1) activates an acidic
      sphingomyelinase.
AB  - Intracellular pathways leading from membrane receptor engagement to apoptotic
      cell death are still poorly characterized. We investigated the intracellular
      signaling generated after cross-linking of CD95 (Fas/Apo-1 antigen), a broadly
      expressed cell surface receptor whose engagement results in triggering of
      cellular apoptotic programs. DX2, a new functional anti-CD95 monoclonal antibody
      was produced by immunizing mice with human CD95-transfected L cells. Crosslinking
      of CD95 with DX2 resulted in the activation of a sphingomyelinase (SMase) in
      promyelocytic U937 cells, as well as in other human tumor cell lines and in CD95
      transfected murine cells, as demonstrated by induction of in vivo sphingomyelin
      (SM) hydrolysis and generation of ceramide. Direct in vitro measurement of
      enzymatic activity within CD95-stimulated U937 cell extracts, using labeled SM
      vesicles as substrates, showed strong SMase activity, which required pH 5.0 for
      optimal substrate hydrolysis. Finally, all CD95-sensitive cell lines tested could
      be induced to undergo apoptosis after exposure to cell-permeant C2-ceramide.
      These data indicate that CD95 cross-linking induces SM breakdown and ceramide
      production through an acidic SMase, thus providing the first information
      regarding early signal generation from CD95, and may be relevant in defining the
      biochemical nature of intracellular messengers leading to apoptotic cell death.

PMID- 7523576
TI  - A large contribution of a cyclic AMP-independent pathway to turtle olfactory
      transduction.
AB  - Although multiple pathways are involved in the olfactory transduction mechanism,
      cAMP-dependent pathway has been considered to contribute mainly to the
      transduction. We examined the degree of contribution of cAMP-independent pathway
      to the turtle olfactory response by recording inward currents from isolated
      cells, nerve impulses from cilia and olfactory bulbar responses. The results
      obtained by the three recordings were essentially consistent with each other, but
      detail studies were carried out by recording the bulbar response to obtain
      quantitative data. Application of an odorant cocktail to the isolated olfactory
      neuron after injection of 1 mM cAMP from the patch pipette elicited a large
      inward current. Mean amplitude of inward currents evoked by the cocktail with 1
      mM cAMP in the patch pipette was similar to that without cAMP in the pipette.
      Application of the cocktail after the response to 50 microM forskolin was adapted
      also induced a large inward current. Application of the odorant cocktail to the
      olfactory epithelium, after the response to 50 microM forskolin was adapted,
      brought about an appreciable increase in the impulse frequency. The bulbar
      response to forskolin alone reached a saturation level around 10 microM. After
      the response to 50 microM forskolin was adapted, 11 species of odorants were
      applied to the olfactory epithelium. The magnitudes of responses to the odorants
      after forskolin were 45-80% of those of the control responses. There was no
      essential difference in the degree of the suppression by forskolin between cAMP-
      and IP3-producing odorants classified in the rat, suggesting that certain part of
      the forskolin-suppressive component was brought about by nonspecific action of
      forskolin. Application of a membrane permeant cAMP analogue, cpt-cAMP elicited a
      large response, and 0.1 mM citralva after 3 mM cpt-cAMP elicited 51% of the
      control response which was close to the response to citralva after 50 microM
      forskolin. A membrane permeant cGMP analogue, db-cGMP elicited a small response
      and the response to 0.1 mM citralva was unaffected by db-cGMP. It was concluded
      that cAMP-independent (probably IP3-independent) pathway greatly contributes to
      the turtle olfactory transduction.

PMID- 7523577
TI  - Characterization of the IgA and subclass IgG responses to neutralizing epitopes
      after infection of pregnant sows with the transmissible gastroenteritis virus or
      the antigenically related porcine respiratory coronavirus.
AB  - In this study, we have investigated the characteristics of secreted IgA and other
      classes of Ig induced after vaccination of sows with transmissible
      gastroenteritis virus (TGEV) or the antigenically related porcine respiratory
      coronavirus (PRCV). Both viruses induced the secretion of neutralizing antibodies
      of different classes in the sows' milk, but these protected suckling piglets
      against TGEV to different degrees. Quantitative differences in the induction of
      IgA by both viruses were found among the different viral antigenic sites and
      subsites of glycoprotein S. In TGEV-vaccinated sows, antigenic subsite A was the
      best inducer of IgA, followed by antigenic site D. After vaccination with PRCV,
      lower levels of IgA were detected on colostrum and milk, antigenic site D and
      subsite Ab being the immunodominant sites. This quantitative difference in
      epitope recognition could explain the differences in newborn piglet protection
      found using Ig classes purified from the milk of sows immunized with both
      viruses. Apparently only IgA recognizing at least antigenic sites A and D confers
      good protection in vivo, whereas any Ig class recognizing only one antigenic site
      may neutralize the virus in cell culture. These results indicate that the
      formulation of a subunit vaccine against TGEV has to consider the inclusion of
      more than one antigenic site involved in virus neutralization.

PMID- 7523575
TI  - Sudden infant death syndrome: a possible primary cause.
AB  - The hypothesis that poisoning by phosphines, arsines and stibines might be the
      primary cause of sudden infant death syndrome (SIDS) was investigated. Most
      mattress materials contain phosphorus or antimony compounds as fire retardant
      additives. Mattress materials in areas affected by the warmth and perspiration of
      the sleeping infant were found to be naturally infected by the fungus
      Scopulariopsis brevicaulis which is thought to be capable of generating
      phosphines, arsines and stibines from materials containing phosphorus, arsenic or
      antimony compounds. These gases may cause anticholinesterase poisoning and
      cardiac failure in infants, but contributory factors include the prone sleeping
      position and overwrapping. In England and Wales, the progressive increase in SIDS
      between 1951 and 1988 seems to be related to increasing use of phosphorus and
      antimony compounds as fire retardents in cot mattresses.

PMID- 7523578
TI  - A rodent cell line permissive for entry and reverse transcription of human
      immunodeficiency virus type 1 has a pre-integration block to productive
      infection.
AB  - Replication of human immunodeficiency virus type 1 (HIV-1) is restricted to CD4
      expressing primate cells. This tropism may be due partly to the absence from
      nonprimate cells of a species-specific factor which has an accessory role to CD4
      during virus penetration. In this study we describe a rat B lymphocyte cell line
      in which there is efficient CD4-dependent entry of HIV-1. However, this cell line
      has a block to productive infection of HIV-1 at a stage between reverse
      transcription and integration. Our results demonstrate that the putative
      accessory factor for HIV-1 penetration is not restricted to primate cells and
      that there is a novel, uncharacterized cell-virus interaction at a stage between
      penetration and integration.

PMID- 7523579
TI  - Hepatitis C virus genotypes, reactivity to recombinant immunoblot assay 2
      antigens and liver disease.
AB  - To clarify the relationship between hepatitis C virus (HCV) genotypes and liver
      disease, we typed HCV genomes in the sera of 151 blood donors, 180 patients with
      type C chronic liver disease (CLD), and 30 haemophiliacs residing in Hiroshima,
      Japan. All of the subjects were positive for anti-HCV and HCV-RNA, and were
      examined for seroreactivity to HCV-specific antigens. The HCV genotypes were
      determined by polymerase chain reaction (PCR) with type-specific primers deduced
      from the putative core region of the HCV genome. Significantly more (P < 0.001)
      type III HCV was found in the samples from the CLD patients (80%) than in those
      from the blood donors (55%). Significantly more (P < 0.001) type III HCV was
      found in the samples from the blood donors (29.1%) than in those from the CLD
      patients (11.7%). There was no significant difference in the distribution of the
      HCV types among the patients with chronic active hepatitis, liver cirrhosis, and
      hepatocellular carcinoma. A four-antigen recombinant immunoblot assay (RIBA-2)
      assay was used to compare the serum samples for their reactivity to a range of
      structural and nonstructural peptides specific for HCV (5-1-1, C100-3, C33c, and
      C22-3). The frequency of seropositivity to 5-1-1 and C100-3 was significantly
      higher (P < 0.001) in type II HCV-infected blood donors than in type III HCV
      infected donors (68.2% and 65.9% vs. 4.5% and 22.7%, respectively). Among the
      type III HCV-infected individuals, the CLD patients had a significantly higher (P
      < 0.01) frequency of seropositivity to 5-1-1 than the blood donors (33.3% vs.
      4.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523582
TI  - A nested case-control study on association between hepatitis C virus antibodies
      and primary liver cancer in a cohort of 9,775 men in Taiwan.
AB  - Most studies on the association between antibodies against hepatitis C virus
      (anti-HCV) and primary liver cancer (PLC) were limited to case-series, or cross
      sectional case-control studies leaving a controversy on causal temporality. A
      nested case-control study on 38 newly-developed PLC patients and 152 matched
      controls selected from a cohort of 9,775 men in Taiwan recruited from September,
      1984, to February, 1986, was carried out to examine the relation between HCV
      infection and PLC. Case-control pairs were matched on age (+/- 1 year),
      residence, and the date at recruitment. Serum samples collected from study
      subjects at the initial recruitment were examined for anti-HCV by enzyme
      immunoassay and hepatitis B surface antigen (HBsAg) by reverse passive
      hemagglutination assay combined with radioimmunoassay. History of cigarette
      smoking, alcohol consumption, vegetable consumption, vegetarian habit, and
      chronic liver diseases were also obtained through standardized interviews
      according to a structured questionnaire at the recruitment. After adjusting for
      HBsAg status and other risk factors, the anti-HCV was significantly associated
      with the development of PLC showing a multivariate-adjusted relative risk of
      88.24. The results suggest that HCV infection may play an important role in the
      etiology of human PLC in Taiwan.

PMID- 7523580
TI  - Expression of hepatitis B surface and core antigens and transforming growth
      factor-alpha in "oval cells" of the liver in patients with hepatocellular
      carcinoma.
AB  - Recent studies have identified epithelial cell populations in human livers that
      are similar to the "oval cells" and "transitional cells" seen in rat livers
      during the early stages of chemical carcinogenesis. It has been suggested that
      these cells might be precursors of hepatocytes and theoretically could be
      involved in hepatocarcinogenesis. The hepatitis B virus (HBV) also is believed to
      play a role in the etiology of hepatocellular carcinoma (HCC). Therefore, a study
      was conducted in nontumorous livers adjacent to HCCs obtained from 26 patients
      from China to determine whether HBV antigens could be identified in oval cells
      and transitional cells using an immunohistochemical technique. Hepatitis B
      surface antigen (HBsAg) was detected in the nontumorous livers of 22/26 (85%)
      patients. HBsAg was detected in oval cells in 18/26 (69%), in transitional cells
      in 21/26 (81%), and in mature hepatocytes in 22/26 (85%), but not in bile duct or
      ductule cells. Transforming growth factor-alpha (TGF-alpha) was expressed in oval
      cells, transitional cells, and bile duct cells in 24/26 (92%) patients, an in
      mature hepatocytes in 25/26 (96%). Coexpression of HBsAg and TGF-alpha was
      identified in the same cells in populations of oval cells and transitional cells
      of selected patients. Because of the possibility that oval cells could be a
      source of evolving HCC, these findings suggest that expression of TGF-alpha
      associated with HBV infection of oval cells could be a mechanism of human
      hepatocarcinogenesis. Thus, oval cells could be a site (or one of the sites)
      where HBV participates in the development of HCC.

PMID- 7523581
TI  - Enhanced detection of antibodies to hepatitis C virus by use of a third
      generation recombinant immunoblot assay.
AB  - Fifty-seven sera with indeterminate results by the second generation RIBA (RIBA
      2) for confirmation of hepatitis C virus (HCV) enzyme linked immunoassay (ELISA)
      reactivity were tested by the new third generation RIBA (RIBA 3). Thirty three
      (57.9%) displayed reactivity for at least one other band and were therefore
      classified as positive; two became negative and 22 (38%) remained indeterminate.
      The incidence of HCV viremia, as determined by the RNA polymerase chain reaction
      (PCR), was 75% for the latter sera. The data show that it is important to subject
      RIBA 3 indeterminate samples to PCR.

PMID- 7523584
TI  - Clorgyline effect on pineal melatonin biosynthesis in Roman high- and low
      avoidance rats.
AB  - Pineal melatonin and related indoles levels were higher in Roman high- than in
      Roman low-avoidance rats, while 5-HIAA/5-HT ratio, as an index of MAO activity
      was higher in low- than in high-avoidance rats. Clorgyline stimulated pineal
      melatonin biosynthesis in both lines of rats. However, melatonin and N
      acetylserotonin levels remained higher and 5-HIAA levels remained lower in the
      high avoidance rats treated with low dose (0.5 mg/kg) while treatment with 1.0
      mg/kg of clorgyline eliminated the differences in melatonin production between
      high- and low-avoidance rats.

PMID- 7523585
TI  - Chronic effect of the irreversible and reversible selective MAO-A inhibitors on
      rat pineal melatonin biosynthesis.
AB  - Acute administration of the irreversible MAO-A inhibitor, clorgyline (2.0 mg/kg,
      s.c.) and the reversible MAO-A inhibitor, moclobemide (10 mg/kg, s.c.), increased
      rat pineal melatonin and related indoles content (HPLC-fluorimetric method).
      Chronic (21 days) administration of clorgyline attenuated the acute effect of
      clorgyline on pineal melatonin biosynthesis. The acute effect of moclobemide on
      melatonin biosynthesis was not affected by chronic moclobemide administration.
      The observed difference in the chronic effects of irreversible and reversible
      selective MAO-A inhibitors on melatonin biosynthesis could have clinical
      implications.

PMID- 7523583
TI  - Epidemiology of hepatitis C virus in western Venezuela: lack of specific antibody
      in Indian communities.
AB  - Hepatitis C virus (HCV) is transmitted mainly by the parenteral route after
      percutaneous exposure to virus-infected products or body fluids. Thus, HCV shares
      with hepatitis B and D (HBV, HDV) viruses this common transmission route. The
      prevalence of antibody against HCV (anti-HCV) was studied in 1155 serum samples
      from individuals at risk of infection by bloodborne or sexually transmitted
      agents, as well as from others lacking such risk factors, from the city of
      Maracaibo, Venezuela. Anti-HCV and serological markers of infection by HBV and
      HDV were also studied in further 550 samples taken from Bari Indians living in
      different communities in the Perija mountains, State of Zulia, Venezuela. The
      results obtained showed that recipients of blood or blood products are at
      increased risk of HCV infection in Maracaibo, whereas sexual transmission plays
      only a minor role if any. Both HBV and HDV infections were highly prevalent among
      Bari Indians (64.4% positive for anti-HBc; 11.1% of HBsAg carriers; 15.3%
      positive for anti-HDV among HBsAg carriers). No anti-HCV positive samples were,
      however, detected among them, thus suggesting either that HCV has not still
      reached this population or that HBV and HDV are transmitted by routes unshared by
      HCV. Anti-HCV was also absent among samples from mentally retarded patients from
      Maracaibo, thus confirming similar findings from other countries and supporting
      the existence of specific transmission mechanisms for HBV and HDV which are not
      working for HCV.

PMID- 7523586
TI  - Epidermal growth factor induces PC12 cell differentiation in the presence of the
      protein kinase inhibitor K-252a.
AB  - The protein kinase inhibitors K-252a and K-252b have been shown earlier to block
      the actions of nerve growth factor and other neurotrophins and, at lower
      concentrations, to selectively potentiate neurotrophin-3 actions. In the present
      study we show that K-252a, but not K-252b, enhances epidermal growth factor (EGF)
      and basic fibroblast growth factor (BFGF)-induced neurite outgrowth of PC12 cells
      at higher concentrations than required for neurotrophin inhibition. In parallel,
      tyrosine phosphorylation of extracellular signal-regulated kinases (Erks)
      elicited by EGF of bFGF was also increased in the presence of K-252a, and this
      signal was prolonged for 6 h. EGF- and bFGF-induced phosphorylation of
      phospholipase C-gamma 1 were not changed. The effect of K-252a on Erks was
      resistant to chronic treatment with phorbol ester, indicating that protein kinase
      C is not involved in this potentiation. In partial contrast to the actions of K
      252a, the neurotrophin-3-potentiating effect of K-252b was accompanied by an
      increase in tyrosine phosphorylation of the Erks and of phospholipase C-gamma 1.
      Finally, although K-252a alone did not induce neurite outgrowth or tyrosine
      phosphorylation of Erks or phospholipase C-gamma 1, this compound alone
      stimulated phosphatidylinositol hydrolysis. Our findings identify activities of K
      252a besides the direct interaction with neurotrophin receptors and suggest that
      a K-252a-sensitive protein kinase or phosphatase might be involved in signal
      transduction of EGF and bFGF. Our results are further compatible with the
      hypothesis that sustained activation of Erks may be important in PC12
      differentiation.

PMID- 7523587
TI  - Leukemia inhibitory factor and ciliary neurotrophic factor increase activated Ras
      in a neuroblastoma cell line and in sympathetic neuron cultures.
AB  - The cytokines leukemia inhibitory factor (LIF) and ciliary neurotrophic factor
      (CNTF) have been implicated in determination of neuronal phenotype as well as
      promotion of neuronal survival. However, the intracellular mechanisms by which
      their signals are transduced remain poorly understood. We have previously studied
      the regulation of vasoactive intestinal polypeptide gene expression by LIF and
      CNTF in the NBFL neuroblastoma cell line. Because these cytokines induce tyrosine
      phosphorylation that may lead to Ras activation, we explored a possible role for
      Ras in LIF- and CNTF-induced signal transduction. In NBFL cells LIF increases
      activated Ras in a rapid, transient, and concentration-dependent manner. CNTF and
      a related cytokine, oncostatin M, produce similar increases. CNTF and LIF also
      increase activated Ras in neuron-enriched dissociated cultures of sympathetic
      ganglia. Moreover, these cytokines rapidly and transiently induce specific
      tyrosine-phosphorylated proteins, p165 and p195. The protein kinase inhibitors
      K252a and staurosporine block LIF-induced increases in tyrosine phosphorylation,
      activated Ras, and vasoactive intestinal polypeptide mRNA in NBFL cells. These
      data support a possible role for Ras in the cell differentiation effects of LIF
      and CNTF.

PMID- 7523588
TI  - Nerve growth factor-induced differentiation in neuroblastoma cells expressing
      TrkA but lacking p75NGFR.
AB  - Nerve growth factor (NGF) binds to two distinct cell surface receptors, TrkA,
      which is a receptor tyrosine kinase, and p75NGFR, whose role in NGF-induced
      signal transduction remains unclear. We have found that human neuroblastoma IMR
      32 cells express TrkA, but p75NGFR expression was not detectable in these cells
      by northern blot analysis, immunoblotting, or chemical crosslinking experiments.
      Despite the lack of p75NGFR expression, subnanomolar concentrations of
      recombinant human NGF induced neurite outgrowth, tyrosine phosphorylation, and
      immediate early gene expression in these cells. These results strongly suggest
      that NGF-induced neuronal differentiation in IMR-32 cells is initiated through
      TrkA in the absence of p75NGFR. Thus, IMR-32 cells may provide a model for
      studying neurotrophic effects of NGF on adult striatal cholinergic neurons, which
      also lack p75NGFR expression.

PMID- 7523589
TI  - Stimulatory effect of histamine on cyclic AMP formation in chick pineal gland.
AB  - Histamine (HA) potently stimulated cyclic AMP accumulation in intact pineal
      glands taken from light-exposed chicks. The action of HA was stronger in the
      presence of forskolin and the phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine (IBMX). The effect of HA was mimicked by HA H1- and H2-receptor
      selective agonists in the following order of potency: HA > 4-methylhistamine (H2)
      > 2-methylhistamine (H1) > 2-thiazolylethylamine (H1) >> dimaprit (H2). The HA H3
      receptor-selective agonist (R)alpha-methylhistamine was poorly active. The effect
      of HA was antagonized by selective H2-receptor blockers (tiotidine > oxmetidine >
      cimetidine = ranitidine) and was not significantly affected by the selective H1-
      and H3-receptor blockers mepyramine and thioperamide. A detailed analysis of an
      antagonistic action of ranitidine (versus HA) revealed a noncompetitive mode of
      action of the H2 blocker. The stimulatory action of the H1 agonist 2
      thiazolylethylamine (both under basal conditions and in the presence of forskolin
      or IBMX) was not significantly influenced by three H1-receptor-selective blockers
      (mepyramine, triprolidine, and diphenhydramine), but it was totally counteracted
      by ranitidine. Using accepted selective agonists and antagonists of the HA H1,
      H2, and H3 receptor we were unable to identify clearly the receptor subtype
      mediating the HA action on the cyclic AMP-generating system of the chick pineal.
      It is suggested that the receptor under consideration may represent either an H2
      like (in terms of mammalian criteria) or avian-specific HA receptor. The data
      suggest that HA may be considered a modulator of the pineal activity in chicks.

PMID- 7523590
TI  - Metabotropic glutamate receptor in C6BU-1 glioma cell has NMDA receptor-ion
      channel complex-like properties and interacts with serotonin2 receptor-stimulated
      signal transduction.
AB  - We found in cultured glioma (C6BU-1) cells that excitatory amino acids (EAAs)
      such as glutamate, N-methyl-D-aspartate (NMDA), aspartate, and metabotropic
      glutamate receptor agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylate
      caused an increase in the inositol 1,4,5-trisphosphate formation and the
      intracellular Ca2+ concentration ([Ca2+]i) in the absence of extracellular Mg2+
      and Ca2+. Pertussis toxin treatment abolished this glutamate-induced [Ca2+]i
      increase. Various antagonists against NMDA receptor-ion channel complex, such as
      Mg2+, D-2-amino-5-phosphonovalerate (D-APV), HA-966, and MK-801, also inhibited
      the increase in [Ca2+]i induced by glutamate. These results indicate that these
      metabotropic EAA receptors coupled to pertussis toxin-susceptible GTP-binding
      protein and phospholipase C system in C6BU-1 glioma cells have the
      pharmacological properties of NMDA receptor-ion channel complexes. We also found
      that in the presence of Mg2+ these metabotropic receptors resemble the NMDA
      receptor-ion channel complex interacted with 5-hydroxytryptamine2 (5-HT2)
      receptor signaling. EAAs inhibited 5-HT2 receptor-mediated intracellular Ca2+
      mobilization and inositol 1,4,5-trisphosphate formation in a concentration
      dependent manner. The inhibitory effect of glutamate was reversed by various NMDA
      receptor antagonists (D-APV, MK-801, phencyclidine, and HA-966), but L-APV failed
      to block the inhibitory effect of glutamate. The same result was observed in the
      absence of extracellular Ca2+. In addition, this inhibitory effect on 5-HT2
      receptor-mediated signal transduction was abolished by treatment of C6BU-1 cells
      with pertussis toxin, whereas 5-HT2 receptor-mediated [Ca2+]i increase was not
      abolished by pertussis toxin treatment. We can, therefore, conclude that the
      inhibitory effect of glutamate is not a result of the influx of Ca2+ through the
      ion channel and that it operates via metabotropic glutamate receptors, having
      NMDA receptor-ion channel complex-like properties and being coupled with
      pertussis toxin-sensitive GTP-binding protein and phospholipase C.

PMID- 7523591
TI  - Neuroprotective effect of hypothermia in cortical cultures exposed to oxygen
      glucose deprivation or excitatory amino acids.
AB  - We examined the effect of moderate hypothermia (30 degrees C) on neuronal injury
      in murine cortical cell cultures. Lowering the temperature during and after a
      period of oxygen-glucose deprivation reduced both the release of glutamate to the
      bathing medium and accompanying neuronal degeneration. Hypothermia immediately
      after brief exposure to high concentrations of NMDA or glutamate also reduced the
      resulting neuronal degeneration. This protective effect was not eliminated when
      MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione were added immediately after
      washout of the exogenously added excitotoxin, suggesting that it was mediated by
      actions additional to reduction of endogenous late glutamate release. Hypothermia
      applied only during exposure to NMDA or glutamate, whether brief or prolonged,
      did not reduce subsequent cytosolic calcium accumulation or neuronal
      degeneration, suggesting that the postsynaptic induction of NMDA receptor
      mediated excitotoxicity is not sensitive to temperature reduction. However,
      hypothermia during prolonged S-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid or kainate exposure did reduce neuronal degeneration.

PMID- 7523592
TI  - Fixed versus removable microdialysis probes for in vivo neurochemical analysis:
      implications for behavioral studies.
AB  - The levels of several neurochemicals, i.e., uric acid (UA), dopamine (DA),
      dihydroxyphenylacetic acid, and 5-hydroxyindoleacetic acid, collected daily from
      the rat striatum with either fixed or removable microdialysis probes for 7 days
      after surgery were compared. The implantation of the fixed cannula was followed
      by a 10-fold increase in the UA content in the dialysates collected from the
      first day after surgery onward and by a steady decrease in dihydroxyphenylacetic
      acid levels, whereas those of DA remained fairly stable. With the removable
      cannula system, only a smaller, transient increase in UA during the first 3 days
      after surgery was observed, with no change in DA or monoamine metabolites. The
      glial reaction around the cannula tracks was assessed by both quantitative
      histological techniques and measuring the glutamine levels in the dialysates
      collected at the time of surgery and 7 days later. Both the glial cell number and
      nuclear size, as well as the glutamine outflow, were considerably larger in the
      animals implanted with the fixed probes. It is, therefore, likely that the UA
      levels in the dialysate reflect the glial reaction to the probe. The suitability
      of the removable probe system for behavioral experiments involving repeated
      microdialysis sampling was illustrated in an experiment showing that the DA
      release in the nucleus accumbens of male rats assessed daily at postsurgery days
      5-10 was virtually identical in three alternating sessions of sexual behavior as
      was the smaller release of this neurotransmitter detected during intervening
      nonsexual social interactions.

PMID- 7523593
TI  - A novel photoaffinity ligand for kainate sites labels two polypeptides with
      molecular mass 45 and 33.5 kDa in chick cerebellum.
AB  - The synthesis of (2S,3S,4S)-4-[1-(4-azidobenzamidomethyl)ethenyl]-2-carboxy-3-
      pyrrolidineacetic acid (ABCPA) is described. This novel kainic acid analogue,
      bearing a photolabile functionality on the isopropenyl side chain, was proven to
      be a good inhibitor of [3H]CNQX and [3H]kainic acid binding on chick cerebellar
      membranes. [3H]ABCPA was photoaffinity cross-linked on the membrane fraction of
      chick cerebellum. Electrophoretic analysis with sodium dodecyl sulfate
      polyacrylamide gel electrophoresis revealed two major radioactive bands with
      apparent molecular masses of 45 and 33.5 kDa. [3H]ABCPA incorporation in both
      bands was completely blocked by 2 mM CNQX. When photoaffinity labeling was
      performed in the presence of 2 mM kainic acid, incorporation of [3H]ABCPA was
      blocked by approximately 70% in the 45-kDa band and by 18% in the 33.5-kDa band.
      Incorporation of radioactivity in both bands was blocked by approximately 30%
      with 10 mM glutamate.

PMID- 7523594
TI  - alpha-Guanidinoglutaric acid, an endogenous convulsant, as a novel nitric oxide
      synthase inhibitor.
AB  - The effects of alpha-guanidinoglutaric acid (GGA), the levels of which were
      increased in the cobalt-induced epileptic focus tissue in the cerebral cortex of
      cats, on brain nitric oxide synthase (NOS) activity were observed. GGA inhibited
      NOS activity in a linear mixed manner (Ki = 2.69 microM) and was as effective as
      NG-monomethyl-L-arginine (MeArg; Ki = 3.51 microM), a well-known NOS inhibitor.
      Although MeArg was synthesized by substituting the guanidino nitrogen of L
      arginine (Arg), GGA was a non-guanidino nitrogen-substituted guanidino compound.
      On the other hand, Arg, which is an endogenous NOS substrate, elevates the
      threshold of seizures induced by GGA. There is evidence that GGA is an
      endogenous, potent, and non-guanidino nitrogen-substituted NOS inhibitor and that
      suppression of nitric oxide biosynthesis may be involved in GGA-induced
      convulsions. Therefore, GGA may be a useful tool in elucidating the chemical
      nature of NOS and the physiological function of nitric oxide.

PMID- 7523595
TI  - RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human brain
      tissue.
AB  - Editing of mRNA in the coding region of the second transmembrane domain of
      glutamate receptor subunits GluR2, GluR5, and GluR6 involves a change of the base
      A in genomic DNA to the base G in mRNA as described in rat brain. To determine
      whether this reaction occurs in humans as well as rats, we studied RNA editing of
      GluR2 and GluR6 in human brain. We compared the extent of editing in controls and
      cases with Huntington's disease. To assay the extent of editing in brain RNA,
      first strand cDNA was amplified using the polymerase chain reaction yielding a
      product across the region of the second transmembrane spanning segment in which
      editing takes place in rats. The PCR product was incubated with the restriction
      enzyme BbvI, which recognizes the sequence GCAGC present in the nonedited
      sequence of the mRNA in subunits GluR2 and GluR6. Thus, BbvI cuts the nonedited
      version but leaves the edited version intact. As in the rat, the GluR2 subunit
      mRNA was completely edited in human brain. The GluR6 subunit was nearly
      completely edited in all gray matter structures investigated including cortex,
      striatum, thalamus, hippocampus, amygdala, and cerebellum with extent of editing
      ranging from 89% in the cerebellum to 95% in the cortex and striatum. No
      significant differences in the extent of RNA editing were apparent in control
      versus Huntington's disease brains. To compare the extent of editing in neurons
      and glia in the brain, editing in cerebral cortex (predominantly gray matter and
      thus neurons) was compared with editing in corpus callosum (white matter and thus
      nearly completely glial cells).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523596
TI  - Transcription and motoneuron size.
AB  - Nuclear size and total RNA synthesis were compared in single lumbar motoneurons
      isolated from the grass frog. Transcription was found to correlate significantly,
      but not exclusively, with nuclear area or volume over a wide range of nuclear
      size, the largest nuclei having the highest mean transcriptional activity. Flow
      cytometric analysis of propidium iodide-stained nuclei excluded polyploidy or
      polyteny as an explanation for the increased transcription, but left open the
      possibility of a small increase in DNA with increasing nuclear size.
      Alternatively, motoneurons may increase transcription and nuclear size without
      increasing their DNA content, possibly by increasing the proportion of dispersed
      chromatin (euchromatin). These two mechanisms for size-related changes in RNA
      synthesis in motoneurons present an interesting contrast to mechanisms used by
      many other large animal cells.

PMID- 7523597
TI  - Biochemical and cellular properties of three immortalized Schwann cell lines
      expressing different levels of the myelin-associated glycoprotein.
AB  - Biochemical and cellular properties of three immortalized Schwann cell lines
      expressing different levels of the myelin-associated glycoprotein (MAG) were
      compared. The S16 line generated by repetitive passaging was described previously
      and expresses a level of MAG comparable to that in adult sciatic nerve. The S42
      line was generated independently by the same procedure, divides more slowly than
      the S16 line, and expresses an even higher level of MAG. The S16Y line arose
      spontaneously from a passage of the S16 cells, divides much more rapidly, and
      does not express MAG. The levels of MAG expression in the three lines are
      inversely related to their rates of proliferation, and MAG mRNA levels parallel
      the amounts of MAG. The S16 and S42 lines consist mainly of flat cells at low
      density and develop many processes at high density, whereas most of the S16Y
      cells are spindle-shaped, resembling primary Schwann cells in appearance. Surface
      immunostaining with the O4 antibody was positive for the S16 and S42 cells and
      negative for the S16Y cells, but all three lines were negative for surface
      staining with the O1 antibody. The overall protein compositions of the three
      lines are very similar, but the S16 and S42 cells express larger amounts of
      several glycoproteins than the S16Y cells, including the adhesion proteins,
      neural cell adhesion molecule, L1, and laminin. S16 and S42 cells (but not S16Y
      cells) also express P0 glycoprotein, galactocerebroside, and sulfatide, but,
      unlike MAG, these other myelin-related components were present at much lower
      levels than in adult nerve. Myelin basic protein and proteolipid protein were not
      detected in any of the lines, although all three lines contained proteolipid
      protein mRNA. 2',3'-Cyclic nucleotide 3'-phosphodiesterase and glial fibrillary
      acidic protein were present in all three lines. Conditions have not yet been
      found in which any of the lines will myelinate dorsal root ganglion neurons in
      vitro, but the S16 and S42 cells differ from the S16Y cells by clustering around
      neurons after 1 week in coculture. In many respects, the S16 and S42 cells
      biochemically resemble Schwann cells at an early stage in their preparation to
      myelinate and should be useful for investigating the cell biology of MAG and
      other myelin-related components.

PMID- 7523598
TI  - Nitric oxide implication in the control of neurosecretion by chromaffin cells.
AB  - In this work, we have studied the effects of pure nitric oxide (NO) on the
      regulation of catecholamine (CA) secretion by chromaffin cells, as well as the
      possible presence of its synthesizing enzyme L-arginine:NO synthase (NOS) in
      these cells. Our results show that NO produces a large stimulation of basal CA
      secretion. This effect was calcium- and concentration-dependent (EC50 = 64 +/- 8
      microM) and was not due to nonspecific damage of the tissue by NO. NO also
      modulates the CA secretion evoked by nicotine in a dose-dependent manner.
      Although it has a stimulatory effect on the CA secretion evoked by low doses of
      nicotine (< 3 microM; EC50 = 16 +/- 3 microM), it produces a dose-dependent
      inhibition of the CA secretion induced by high doses of nicotine (> or = 30
      microM; IC50 = 52 +/- 6 microM). The mechanism by which NO modulates CA secretion
      seems to be through the increase in the cyclic GMP levels, because there was a
      close correlation between the CA secretion and the cyclic GMP levels. The
      presence of a specific activity of NOS in chromaffin cells has been demonstrated
      by two independent methods: release of [14C]citrulline from [14C]arginine and
      formation of an NO-hemoglobin complex. NOS activity was about 0.5 pmol/min/mg of
      protein. It was calcium- and mainly calmodulin-dependent and could be
      specifically blocked by the NOS inhibitor N-methyl-L-arginine. These results
      suggest that NO could be an important intracellular messenger in the regulation
      of neurosecretion in chromaffin cells.

PMID- 7523599
TI  - Interactions between N-acetylaspartylglutamate and AMPA, kainate, and NMDA
      binding sites.
AB  - The structure of N-acetylaspartylglutamate (NAAG) suggests this neuronal
      dipeptide as a candidate for interaction with discrete subclasses of ionotropic
      and metabotropic acidic amino acid receptors. A substantial difficulty in the
      assay of these interactions is posed by membrane-bound peptidase activity that
      converts the dipeptide to glutamate and N-acetylaspartate, molecules that will
      interfere with receptor assays. We have developed two sets of unique receptor
      assay conditions and applied one standard assay to measure the interactions,
      under equilibrium binding conditions, of [3H]kainate, [3H]amino-3-hydroxy-5
      methylisoxazole-4-propionic acid ([3H]AMPA), and [3H]CGS-19755 with the three
      classes (kainate, quisqualate, and N-methyl-D-aspartate) of ionotropic glutamate
      receptors, while inhibiting peptidase activity against NAAG. Under these
      conditions, NAAG exhibits apparent inhibition constants (IC50) of 500, 790, and
      8.8 microM in the kainate, AMPA, and CGS-19755 receptor binding assays,
      respectively. Glutamate was substantially more effective and less specific in
      these competition assays, with inhibition constants of 0.36, 1.1, and 0.37
      microM. These data support the hypothesis that, relative to glutamate, NAAG
      functions as a specific, low potency agonist at N-methyl-D-aspartate subclass of
      ionotropic acidic amino acid receptors, but the peptide is not likely to activate
      directly the kainate or quisqualate subclasses of excitatory ionotropic receptors
      under physiologic conditions.

PMID- 7523600
TI  - 3-Nitropropionic acid toxicity in the striatum.
AB  - We examined the effects of chronic systemic administration of the mitochondrial
      toxin 3-nitropropionic acid (3-NP) in doses ranging from 12 to 16 mg/kg/day for
      30 days on striatal cytoarchitecture in rats. Administration of 3-NP at a dose of
      16 mg/kg/day resulted in large lesions with a central necrotic core that was
      depleted of both neurons and glia. Glial fibrillary acidic protein (GFAP) gene
      expression was decreased in the lesion core, whereas the tissue surrounding this
      area showed a massive increase in signal intensity. Enkephalin and substance P
      mRNA expression in the striatum showed dose-dependent decreases following
      administration of 3-NP. A substantial decrease occurred even in animals treated
      with 3-NP at a dose of 12 mg/kg/day, in which there was little discernible
      neuronal loss and no increase in GFAP gene expression. In contrast to the
      decrease in enkephalin and substance P mRNA expression, somatostatin mRNA
      expressing neurons were largely preserved. There was no preferential loss of
      [3H]naloxone patches in the rat striatum following chronic administration of 3
      NP. In animals treated with 12-15 mg/kg/day neither the area nor binding density
      of the patches was changed. To study the effect of 3-NP on N-methyl-D-aspartate
      (NMDA)-gated Ca2+ channels we used in vivo administration of [3H]MK-801. Three
      hours after a single injection of 3-NP at a dose of 30 mg/kg there was a three-
      to fivefold increase in [3H]MK-801 binding in cortex and striatum as compared
      with saline-treated animals, consistent with an activation of NMDA receptors.

PMID- 7523601
TI  - Membrane clustering and bungarotoxin binding by the nicotinic acetylcholine
      receptor: role of the beta subunit.
AB  - Nicotinic acetylcholine receptors (nAChRs) are localised at morphologically
      distinct regions of the post-synaptic membrane by interactions between the
      receptor subunits and cytoskeletal proteins, such as the 43-kDa protein. We have
      used Xenopus oocytes to examine the localisation and pharmacological properties
      of muscle nAChRs associated with 43-kDa protein and to compare them with hybrid
      muscle nAChRs containing a beta subunit derived from a neuronal source. Receptors
      expressed on the oocyte outer membrane were visualised using confocal scanning
      laser microscopy. Coexpression of mouse muscle subunit alpha 1 beta 1 gamma delta
      and 43-kDa protein transcripts produced discrete receptor aggregates with a
      diameter of 1-5 microns whose function was partially blocked by application of
      neuronal bungarotoxin (NBT) at 100 nM. Substitution of the beta 1 subunit by the
      neuronal beta 2 protein produced a functioning receptor that did not aggregate in
      the presence of 43-kDa protein and was substantially blocked by the same
      concentration of NBT. Hybrid alpha 1 beta 4 gamma delta receptors exhibited a
      combination of characteristics in that they clustered like normal muscle subunits
      in the presence of 43-kDa protein, but showed a sensitivity to NBT intermediate
      between that of muscle receptors and that of hybrids containing beta 2. These
      results suggest that the beta subunit is an important determinant in receptor
      localisation and sensitivity to NBT.

PMID- 7523602
TI  - Appearance of depolarization- and maitotoxin-induced [Ca2+]i elevation in single
      LAN-1 human neuroblastoma cells on exposure to retinoic acid.
AB  - LAN-1 is a human neuroblastoma cell line that, in the undifferentiated state,
      does not respond to membrane depolarization with an elevation of [Ca2+]i,
      monitored by fura-2 single-cell microfluorimetry. The exposure of LAN-1 cells to
      the differentiating agent retinoic acid induced the appearance of [Ca2+]i
      elevation elicited by 55 mM K+. Maitotoxin, a putative activator of voltage
      sensitive Ca2+ channels, did not evoke an elevation of [Ca2+]i in
      undifferentiated LAN-1 cells, but produced a marked and sustained increase in
      [Ca2+]i when superfused in retinoic acid-treated cells. Both high K(+)- and
      maitotoxin-induced [Ca2+]i elevation in retinoic acid-differentiated LAN-1 cells
      was reversed by the lanthanide Gd3+, an inorganic Ca(2+)-entry blocker, and by
      the snail toxin omega-conotoxin GVIA, which interacts with the N subtype of
      voltage-sensitive Ca2+ channels. In contrast, both Bay K 8644 and nimodipine,
      dihydropyridines that selectively activate or block, respectively, the L-channel
      subtype, were completely ineffective. The tumor promoter phorbol 12-myristate 13
      acetate (100 nM), a protein kinase C activator, inhibited the elevation of
      [Ca2+]i due to Ca2+ influx elicited by membrane depolarization. K(+)-induced
      [Ca2+]i elevation appeared 24 h after the addition of retinoic acid and reached
      the highest magnitude after 72 h. Furthermore, 8 days after the removal of the
      differentiating agent from the culture medium, the high K(+)-induced increase of
      [Ca2+]i was still present.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523603
TI  - No linkage or association between multiple sclerosis and the myelin basic protein
      gene in affected sibling pairs.
AB  - Myelin basic protein was examined as a candidate gene for susceptibility to
      multiple sclerosis using two adjacent amplification fragment length polymorphisms
      (AmpFLPs), containing seven and six highly informative alleles respectively. No
      allelic association was found with multiple sclerosis, comparing 77 cases and 88
      controls, and there was no evidence for linkage in 73 affected sibling pairs,
      using the methods of identity by descent and identity by state.

PMID- 7523604
TI  - Tenascin in cerebrospinal fluid is a useful biomarker for the diagnosis of brain
      tumour.
AB  - Tenascin, an extracellular matrix glycoprotein, has been reported to be expressed
      predominantly on glioma tissue in the CNS, both in a cell associated and an
      excreted form. Recently, a highly sensitive sandwich type enzyme immunoassay for
      quantitative determination of tenascin was developed. In the present study, the
      amount of tenascin in CSF was measured. An increase of tenascin in CSF (> 100
      ng/ml) was found in patients with an astrocytic tumour. The concentration was
      significantly higher (> 300 ng/ml) in high grade astrocytoma (anaplastic
      astrocytoma and glioblastoma) and a further increase (> 1000 ng/ml) was found in
      cases of CSF dissemination of high grade astrocytoma. On the other hand, tenascin
      concentrations were less than 100 ng/ml in non-astrocytic tumours and non
      neoplastic neurological diseases, except meningeal dissemination of tumour cells,
      meningeal stimulation by infection, and subarachnoid haemorrhage. In cases of
      treated astrocytomas in remission, tenascin was negligible (< 100 ng/ml) in the
      CSF. The measurement of tenascin in CSF is useful for differential diagnosis of
      brain tumours and monitoring of astrocytic tumours.

PMID- 7523605
TI  - Expression of P0 protein in sural nerve of a patient with hereditary motor and
      sensory neuropathy type III.
AB  - We present expression of Po protein and Po mRNA on the sural nerve of a patient
      with hereditary motor and sensory neuropathy type III. This patient was
      identified with a point mutation in Po gene, which resulted in the substitution
      of glycine for arginine in transmembrane domain of P0 protein. An electron
      microscopic examination revealed very thin myelinated fibers surrounded by
      multilamellated onion bulbs composed with greatly proliferated Schwann cells. An
      immunocytochemical and immunoblot analysis is showed P0 protein normally
      expressed in myelin on the sural nerve. By in situ hybridization, mRNA of P0
      protein was detected at normal levels in Schwann cell cytoplasm. Those
      observations indicated that there was no truncated myelin P0 protein in
      peripheral nerve of this patient.

PMID- 7523607
TI  - Diffuse small noncleaved-cell, non-Burkitt's lymphoma in adults: a high-grade
      lymphoma responsive to ProMACE-based combination chemotherapy.
AB  - PURPOSE: To review the efficacy of cyclophosphamide, doxorubicin, etoposide,
      methotrexate with leucovorin, and prednisone (ProMACE)-based combination
      chemotherapy programs in the treatment of patients with diffuse small noncleaved
      cell non-Burkitt's lymphoma. PATIENTS AND METHODS: Thirty-three patients with
      diffuse small noncleaved-cell non-Burkitt's lymphoma were accrued: eight with
      localized disease were treated with modified ProMACE-mechlorethamine,
      vincristine, procarbazine, and prednisone (MOPP) plus involved-field radiation
      therapy, and 25 with advanced-stage disease were treated with ProMACE/MOPP
      flexitherapy (n = 8), ProMACE-MOPP (n = 9), or ProMACE-cytarabine, bleomycin,
      vincristine, and methotrexate with leucovorin (CytaBOM) (n = 8). The median
      follow-up duration is 10 years. RESULTS: All eight patients with localized
      disease achieved a complete response, none have relapsed, and one died of
      intercurrent illness. Among patients with advanced-stage disease, five of eight
      (63%) flexitherapy-treated patients, six of nine (67%) ProMACE-MOPP-treated
      patients, and eight of eight (100%) ProMACE-CytaBOM-treated patients achieved a
      complete response. If the two ProMACE-MOPP-based groups are considered together,
      disease-free and overall survival rates at 15 years are projected at 61% and 35%,
      respectively. In contrast, only one patient has relapsed from a ProMACE-CytaBOM
      induced complete remission, and overall survival of ProMACE-CytaBOM-treated
      patients (88%) is significantly higher than that for flexitherapy and ProMACE
      MOPP (P2 = .04). CONCLUSION: Adult patients with diffuse small non-cleaved-cell
      non-Burkitt's lymphoma may be effectively treated with regimens that are
      effective in other aggressive lymphomas (eg, diffuse large-cell lymphoma).

PMID- 7523606
TI  - Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory
      adenocarcinoma of the prostate.
AB  - PURPOSE: Estramustine and etoposide (VP-16) have been demonstrated to inhibit the
      growth of prostate cancer cells in experimental models. This led us to evaluate
      the effectiveness of this combination in the treatment of patients with
      metastatic prostate carcinoma refractory to hormone therapy. PATIENTS AND
      METHODS: Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d, were administered orally
      in divided doses for 21 days. Patients were then taken off therapy for 7 days and
      the cycle then repeated. Therapy continued until evidence of disease progression.
      RESULTS: Forty-two patients have been enrolled onto this trial with a minimum of
      40 weeks follow-up. Of 18 patients with measurable soft tissue disease, three
      demonstrated a complete response (CR) and six a partial response (PR) for longer
      than 2 months. Of these 18 patients, pretreatment prostate-specific antigen (PSA)
      levels decreased by at least 75% in five men (28%) and by at least 50% in nine
      (50%). The median survival duration has not been reached in those patients who
      demonstrated a response either by soft tissue or PSA criteria. Of 24 patients
      with disease limited to bone, six (25%) demonstrated improvement and nine (38%)
      demonstrated stability in their bone scans. Five men (21%) demonstrated a
      decrease of at least 75% in pretreatment PSA levels and 14 (58%) demonstrated at
      least a 50% decrease; the median survival duration has not been reached in these
      patients. Pretreatment performance status is an important predictor of survival.
      CONCLUSION: We conclude that the combination of estramustine and VP-16 is an
      active oral regimen in hormone-refractory prostate cancer.

PMID- 7523608
TI  - ABVD/MOPP and low-dose involved-field radiotherapy in pediatric Hodgkin's
      disease: the Stanford experience.
AB  - PURPOSE: We reported previously that treatment with six cycles of
      mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy
      and 15 to 25 Gy irradiation was effective in curing children with Hodgkin's
      disease, but was associated with a 6.5% 10-year risk of development of secondary
      leukemia. Based on the results of that study, a successor study was designed with
      the objective to maintain treatment efficacy while decreasing adverse effects,
      particularly the occurrence of secondary leukemia. PATIENTS AND METHODS: Fifty
      seven children with a chronologic and/or bone age less than 16 years were
      enrolled onto this study between May 1982 and October 1990. Treatment consisted
      of six cycles of combination chemotherapy--three of doxorubicin, bleomycin,
      vinblastine, and dacarbazine (ABVD) and three of MOPP--and low-dose irradiation
      (15 Gy) of involved fields. Boosts of 10 Gy were given to areas of bulky disease
      and to those that did not respond completely after two cycles of chemotherapy.
      RESULTS: With a median follow-up duration of 6.7 years, the projected 10-year
      survival and event-free survival (EFS) rates are 96% (SE 2.5%) and 93% (SE 3.5%)
      for the entire cohort of 57 patients, and 85% (SE 10%) and 69% (SE 12.8%),
      respectively, for 13 patients with stage IV disease. No patient has developed a
      second malignancy. Growth and development have progressed normally. No patients
      have symptomatic cardiac, pulmonary, or thyroid disease. Subclinical
      abnormalities of pulmonary function were detected in 32% and chemical
      hypothyroidism in 16%. CONCLUSION: This therapy was highly efficacious in
      children with Hodgkin's disease without unacceptable toxicity. Future efforts
      should be directed toward further reducing therapy for favorable early-stage
      patients and improving treatment efficacy for those with stage IV disease.

PMID- 7523610
TI  - Reconstruction of hippocampal CA1 pyramidal cell electrophysiology by computer
      simulation.
AB  - 1. We have developed a 16-compartment model that reproduces most of the features
      of the CA1 pyramidal cell electrophysiology observed experimentally. The model
      was constructed using seven active ionic conductances: gNa, gCa, gDR, gCT, gA,
      gM, and gAHP whose kinetics have been, inferred, in most cases, from the
      available voltage-clamp data obtained from these cells. We focussed the
      simulation on the initial and late accommodation, the slow depolarization
      potential and the spike broadening during repetitive firing, because their
      mechanisms are not well understood. 2. Current-clamp records were reproduced by
      iterative adjustments to the ionic maximum conductances, scaling and/or
      "reshaping" of the gates' time constant within the experimental voltage-clamp
      data, and shifting the position of the steady-state gate opening. The final
      properties of the ionic channels were not significantly different from the
      voltage-clamp experiments. 3. The resulting model reproduces all four after
      potentials that have been recorded to follow activation of the cell. The fast,
      medium, and slow after-hyperpolarization potentials (AHPs) were, respectively,
      generated by ICT, IM, and IAHP. Furthermore, the model suggests that the
      mechanisms underlying the depolarization after potential (DAP) is mostly due to
      passive recharging of the soma by the dendrites. 4. The model also reproduces
      most of the firing features experimentally observed during injection of long
      current pulses. Model responses showed a small initial decrease in the firing
      frequency during a slow underlying depolarization potential, followed by a more
      significant frequency decrease. Moreover, a gradual broadening of the action
      potential and loss of the fast AHP were also observed during the initial high
      frequency firing, followed, as the firing frequency decreased, by a gradual
      recovery of the spikes' original width and fast AHP amplitude increase. 5. A
      large reduction of the K repolarizing current was required to reproduce the spike
      broadening and reduction of the fast AHP experimentally observed in CA1 cells
      during repetitive firing responses. The incorporation of a transient Ca- and
      voltage-dependent K current (ICT) into the model successfully reproduced these
      experimental observations. In contrast, we were unable to reproduce this
      phenomenon when a large persistent Ca- and voltage-dependent K current (generally
      named IC) was included in the model. These results suggest that there is a strong
      contribution to action-potential repolarization and fast AHP by a transient Ca-
      and voltage-dependent K current (ICT). 6. The two accommodation steps were
      induced by a progressively enlargement of two K currents IM (initial) and IAHP
      (late).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523609
TI  - High-dose therapy followed by autologous peripheral-blood stem-cell
      transplantation for patients with Hodgkin's disease and non-Hodgkin's lymphoma
      using unprimed and granulocyte colony-stimulating factor-mobilized peripheral
      blood stem cells.
AB  - PURPOSE: To evaluate (1) the effect of granulocyte colony-stimulating factor (G
      CSF) on peripheral-blood stem-cell (PBSC) mobilization; (2) the rate of
      hematopoietic recovery after G-CSF-mobilized PBSC transplantation; and (3) the
      outcome of high-dose myeloablative therapy and PBSC transplantation in patients
      with relapsed or refractory lymphoma. PATIENTS AND METHODS: Ninety-five patients
      with lymphoma underwent high-dose therapy followed by PBSC transplant in three
      sequentially treated cohorts of patients in a nonrandomized study. The first 30
      patients received nonmobilized PBSCs (unprimed) without G-CSF after transplant,
      the next 26 patients received PBSC that were mobilized with G-CSF 5
      micrograms/kg/d (primed-5) plus G-CSF after transplant, and the last 39 patients
      received PBSC mobilized by G-CSF 10 micrograms/kg/d (primed-10) plus G-CSF after
      transplant. The conditioning regimen consisted of fractionated total-body
      irradiation (FTBI) 12 Gy in combination with etoposide 60 mg/kg and
      cyclophosphamide 100 mg/kg. Patients with prior radiotherapy received carmustine
      (BCNU) 450 mg/m2 instead of FTBI. RESULTS: The use of G-CSF-mobilized PBSCs in
      combination with G-CSF posttransplant resulted in a significantly accelerated
      time to recovery of both granulocyte and platelet when compared with the unprimed
      group. The median number of days to an absolute granulocyte count (ANC) of
      greater than 0.5 x 10(9)/L was 10 days for G-CSF primed versus 20 days for the
      unprimed (P = .0001). The median days to platelet transfusion independence was 16
      and 31 days (P = .0001) for the G-CSF primed and unprimed, respectively. There
      were also significant reductions in the number of platelet (P = .02) and RBC
      transfusions (P = .006) for the G-CSF primed. Multivariate analysis of prognostic
      factors identified CD34+ cell dose as the only additional factor predicting
      engraftment. Sixty-nine patients are alive at a median follow-up of 15.9 months
      (range, 7.4 to 63.7). The cumulative probability of 2-year disease-free survival
      is 59% (95% confidence interval [CI], 36% to 79%) and 39% (95% CI 25% to 55%) for
      patients with Hodgkin's disease and non-Hodgkin's lymphoma, respectively.
      CONCLUSION: The use of G-CSF-mobilized PBSC after high-dose myeloablative therapy
      resulted in a rapid, complete, and sustained hematopoietic recovery. Disease-free
      survival over 2 years can be achieved in some patients with relapsed lymphoma
      after high-dose therapy and PBSC transplantation. However, longer follow-up is
      required to confirm the curability of this approach.

PMID- 7523611
TI  - Characterization of the membrane ion currents of a model molluscan muscle, the
      accessory radula closer muscle of Aplysia california. I. Hyperpolarization
      activated currents.
AB  - 1. The simple neuromuscular circuit consisting of the accessory radula closer
      (ARC) muscle of the mollus Aplysia californica together with its innervating
      motor and modulatory neurons has been extensively studied as a model preparation
      in which it might be possible to reach an integrated understanding of the neural
      and cellular mechanisms of behavioral plasticity, in this case of a component of
      Aplysia feeding behavior. Previous work has suggested that much of the plasticity
      of this behavior is implemented by appropriate release of modulatory
      neurotransmitters and peptide cotransmitters that modulate several parameters of
      the contractions of the ARC muscle. However, little is as yet known about the
      underlying cellular mechanisms. 2. We have begun to study single, functionally
      intact fibers dissociated from the ARC muscle to assess to what extent the
      modulation of its contraction might be mediated by one candidate mechanism,
      modulation of its membrane ion currents. First, however, it was necessary to gain
      a thorough understanding of the unmodulated currents and their likely roles in
      normal contraction. Using voltage-clamp techniques, we have therefore identified
      and characterized the major currents present in the ARC muscle fibers. We
      describe these currents in this and the following two papers. These results
      constitute the first detailed description of ion currents in a molluscan muscle
      and lay the foundation for further study, to be presented in subsequent papers,
      of the roles of two currents that we have indeed found to be modulated in ways
      likely to contribute to the modulation of contraction. 3. In this paper we first
      describe the general electrophysiological characteristics of the dissociated
      fibers and present evidence that the fibers can be adequately space clamped. 4.
      The physiological operating voltage range of the nonspiking ARC muscle most
      likely extends from about -80 to about -25 mV. The steady-state current-voltage
      (I-V) relation of total membrane current rectifies inwardly in the negative and
      outwardly in the positive portion of this voltage range, with a plateau region of
      high or even negative slope resistance separating the two regions of
      rectification. 5. The current responsible for the inward rectification at
      negative voltages is a classical inwardly rectifying K current. It is activated
      by hyperpolarization with quasi-instantaneous kinetics; its whole I-V relation
      shifts along the voltage axis in a Nernstian manner with altered extracellular K+
      concentration; it is blocked by low extracellular Ba2+ and Cs+, and the block is
      promoted by hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523612
TI  - Effects of inhibition and dendritic saturation in simulated neocortical pyramidal
      cells.
AB  - 1. We have used compartmental models of reconstructed pyramidal neurons from
      layers 2 and 5 of cat visual cortex to investigate the nonlinear summation of
      excitatory synaptic input and the effectiveness of inhibitory input in countering
      this excitation. 2. In simulations that match the conditions of a recent
      experiment, dendritic saturation was significant for physiological levels of
      synaptic activation: a compound excitatory postsynaptic potential (EPSP)
      electrically evoked during a depolarization caused by physiological synaptic
      activation was decreased by up to 80% compared with an EPSP evoked at rest. 3.
      Synaptic inhibition must be coactivated with excitation to quantitatively match
      the experimental results. The experimentally observed coactivation of inhibition
      with excitation produced additional current shunts that amplified the decrease in
      test EPSP amplitude. About 30% of the experimentally observed decrease in EPSP
      amplitude was caused by decreases in input resistance (Rin) due to synaptic
      conductance changes; a reduced driving force accounted for the remaining
      decrease. 4. The amount of inhibition was then increased by nearly an order of
      magnitude, to approximately 10% of the total number of inhibitory synapses on a
      typical cortical pyramidal cell. The sustained firing of this many inhibitory
      inputs was sufficient to completely suppress the firing of a neuron receiving
      strong excitatory input. However, this level of inhibition produced a very large
      reduction in Rin. Such large reductions in Rin have not been observed
      experimentally, suggesting that inhibition in cortex does not act to veto (shunt)
      strong, sustained excitatory input (of order 100 ms). 5. We propose instead that
      strong, transient activation (< 10 ms) of a neuron's inhibitory inputs,
      sufficient to briefly prevent firing, is used to shape the temporal structure of
      the cell's output spike train. Specifically, cortical inhibition may serve to
      synchronize the firing of groups of pyramidal cells during optimal stimulation.

PMID- 7523613
TI  - A- and C-type rat nodose sensory neurons: model interpretations of dynamic
      discharge characteristics.
AB  - 1. Neurons of the nodose ganglia provide the sole connection between many types
      of visceral sensory inputs and the central nervous system. Electrophysiological
      studies of isolated nodose neurons provide a practical means of measuring
      individual cell membrane currents and assessing their putative contributions to
      the overall response properties of the neuron and its terminations. Here, we
      present a comprehensive mathematical model of an isolated nodose sensory neuron
      that is based upon numerical fits to quantitative voltage- and current-clamp data
      recorded in our laboratory. Model development was accomplished using an iterative
      process of electrophysiological recordings, nonlinear parameter estimation, and
      computer simulation. This work is part of an integrative effort aimed at
      identifying and characterizing the fundamental ionic mechanisms participating in
      the afferent neuronal limb of the baroreceptor reflex. 2. The neuronal model
      consists of two parts: a Hodgkin-Huxley-type membrane model coupled to a lumped
      fluid compartment model that describes Ca2+ ion concentration dynamics within the
      intracellular and external perineuronal media. Calcium buffering via a calmodulin
      type buffer is provided within the intracellular compartment. 3. The complete
      model accurately reproduces whole-cell voltage-clamp recordings of the major ion
      channel currents observed in enzymatically dispersed nodose sensory neurons.
      Specifically, two Na+ currents exhibiting fast (INaf) and slow tetrodotoxin (TTX)
      insensitive (INas) kinetics; low- and high-threshold Ca2+ currents exhibiting
      transient (ICa,t) and long-lasting (ICa,n) dynamics, respectively; and outward K+
      currents consisting of a delayed-rectifier current (IK), a transient outward
      current (I(t)) and a Ca(2+)-activated K+ current (IK,Ca). 4. Whole-cell current
      clamp recordings of somatic action-potential dynamics were performed on
      enzymatically dispersed nodose neurons using the perforated patch-clamp
      technique. Stimulus protocols consisted of both short (< or = 2.0 ms) and long (>
      or = 200 ms) duration current pulses over a wide range of membrane holding
      potentials. These studies clearly revealed two populations of nodose neurons,
      often termed A- and C-type cells, which exhibit markedly different action
      potential signatures and stimulus response properties. 5. Using a single set of
      equations, the model accurately reproduces the electrical behavior of both A- and
      C-type nodose neurons in response to a wide variety of stimulus conditions and
      membrane holding potentials. The structure of the model, as well as the majority
      of its parameters are the same for both A- and C-type implementations.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7523615
TI  - Stress in the dental office.
AB  - Stress is endemic and epidemic in today's fast-paced world, and dentists are not
      immune. While stressors are particular to the individual, some factors
      potentially causing stress in the dental office are economic conditions,
      difficult patients, inherent personality traits and physical constraints.

PMID- 7523616
TI  - Habits of highly effective dentists.
AB  - While stress is pervasive in the world today, and particularly in the dental
      office, coping strategies can counteract it. This paper discusses the personality
      features of the hardy dentist; the fact that stress and its effects depend
      largely on individual perception of stressors; and five habits to develop for
      stress reduction: seeking information, taking direct action, inhibiting action,
      engaging intrapsychic efforts and calling on others.

PMID- 7523617
TI  - Periodontal screening and recording.
AB  - The perceived benefits of PSR as a simple, sensitive and efficient tool to screen
      patients for periodontal diseases have contributed to its incorporation into the
      dental practice environment. The recent introduction of PSR to the public
      probably will motivate patients to seek more information about periodontal
      health. Used as a communication and screening tool, PSR has the potential to
      enhance professional and patient relationships through cooperative treatment
      planning and increased patient treatment acceptance.

PMID- 7523618
TI  - The adhesive-corrected implant framework.
AB  - To avoid stress between bone, implant and supra construction, the connection
      between implants must be passive. This is clinically difficult, if not
      impossible, to achieve with current procedures. Two techniques are presented in
      which pre-machined titanium abutment cylinders or discs are intra-orally luted to
      a cast supra structure. The objective is to create a stress-free implant frame
      work connection. Possible advantages and disadvantages are discussed.

PMID- 7523619
TI  - A whole new era!

PMID- 7523620
TI  - The art of personal suffering.

PMID- 7523614
TI  - Interstitial volume changes during spreading depression (SD) and SD-like hypoxic
      depolarization in hippocampal tissue slices.
AB  - 1. Relative interstitial volume (ISV) was estimated from the concentration
      changes of iontophoretically administered tetramethyl- and tetraethylammonium
      (TMA+ and TEA+). Spreading depression (SD) was provoked by high K+, and hypoxic
      SD-like depolarization (HSD) was induced by withdrawing oxygen. 2. Probe ion
      concentrations increased dramatically and about equally during SD and HSD, except
      that in a few hypoxic trials signals became transiently smaller than control.
      Interstitial volume appeared to decrease on the average by approximately 70%. 3.
      The ISV that remains patent in CA1 region at the height of SD is < 4% of total
      tissue volume. Probe ions may occasionally have passed through cell membranes for
      a short time during hypoxic SD.

PMID- 7523621
TI  - Board certification--what does it mean?

PMID- 7523624
TI  - Diagnosis and treatment of trigeminal nerve injuries.
AB  - Microneurosurgery has become a valuable technique in the field of oral and
      maxillofacial surgery. It is now possible to microsurgically repair injuries to
      the inferior alveolar and lingual nerves resulting from routine oral surgery or
      dental or oncologic treatment. Sensation may be improved or restored, and painful
      pares thesias relieved, by timely, well-performed microsurgery.

PMID- 7523622
TI  - Dental outpatient general anesthesia.
AB  - Oral and maxillofacial surgeons have established and maintained a record of
      safety in using general anesthesia for outpatient dental care. The history of
      anesthesia use in dentistry is reviewed, as well as numerous changes over the
      last 20 years.

PMID- 7523625
TI  - Consultation for facial aesthetics.
AB  - This article highlights the important aspects of facial aesthetics to help
      readers direct their patients to appropriate cosmetic consultations. Important
      facial landmarks are defined and the specific facelift procedures to improve the
      aesthetics of these areas are identified. Armed with this information, the
      general dentist can perform a more complete assessment and be better able to
      focus on the true concerns of the patient.

PMID- 7523623
TI  - In vitro comparison of the effectiveness of three surface disinfectants.
AB  - Choosing a general purpose surface disinfectant for the dental office environment
      is difficult because of the wide range of products available, varying claims by
      manufacturers and contradictory reports in the literature regarding product
      efficacy. This study tested the antimicrobial effectiveness of diluted-for-use O
      phenyl-phenol (Omni), didecyl dimethyl ammonium (Basic G) and isopropanol
      (Virahol). Products were tested for antimicrobial activity at 0, 12 and 24 hours,
      3, 6 and 8 days. O-phenyl-phenol demonstrated essentially no antibacterial effect
      against any of eleven test microorganisms. Didecyl dimethyl ammonium and the
      isopropanol reagent both demonstrated statistically significant killing activity
      against all organisms. More importantly, these two products maintained their
      antimicrobial activity up to 8 days after preparation.

PMID- 7523626
TI  - Impactions: observe or treat?
AB  - In the modern population, few third molars erupt normally and have a good long
      term prognosis. This paper reviews the etiology and potential pathology of
      impacted teeth, and discusses indications and contraindications for extraction.

PMID- 7523627
TI  - Functional properties and substrate specificity of the cloned L-glutamate/L
      aspartate transporter GLAST-1 from rat brain expressed in Xenopus oocytes.
AB  - The rat brain L-glutamate/L-aspartate transporter GLAST-1 is a member of a family
      of Na(+)-dependent high-affinity L-glutamate transporters proposed to be involved
      in the termination and modulation of excitatory neurotransmitter signals.
      Application of electrophysiological and radiotracer techniques on Xenopus oocytes
      expressing cloned GLAST-1 revealed that the apparent Km value of the transporter
      for L-glutamate and Na+ ions did not depend on voltage while the maximal
      transport rate increased with more negative potentials, indicative of a low-field
      access channel. The apparent Km value of the transporter for L-glutamate depends
      on the Na+ concentration, suggesting that substrate and ions are transported by
      GLAST-1 in a simultaneous manner. All of the L-glutamate uptake blockers tested
      either were substrates or did not affect the current induced by L-glutamate. The
      changes in the amplitude of the current induced by simultaneous application of
      two substrates can be interpreted by a competition for one binding site.

PMID- 7523628
TI  - A rhodopsin gene mutation responsible for autosomal dominant retinitis pigmentosa
      results in a protein that is defective in localization to the photoreceptor outer
      segment.
AB  - Over 45 mutations in the rhodopsin gene have been identified in patients with
      autosomal dominant retinitis pigmentosa, including a cluster near the extreme
      carboxy-terminus, a region of the protein for which no function has yet been
      assigned. To elucidate the biochemical defect(s) in this group of mutants, we
      have studied a naturally occurring stop codon mutation that removes the last five
      amino acids of rhodopsin (Q344ter). When produced in transfected tissue culture
      cells, the mutant protein is indistinguishable from the wild type in light
      dependent activation of the photoreceptor G-protein (transducin), and in serving
      as a light-dependent substrate for rhodopskin kinase. Mice that express a Q344ter
      transgene in rod photoreceptors show nearly normal light responses as determined
      by suction electrode recordings of the membrane current from single rod outer
      segments; the main difference between transgenic and nontransgenic responses is a
      15% longer time-to-peak in the response of transgenic rods. In the Q344ter
      transgenic retina, direct immunofluorescent staining with antibodies specific for
      either wild-type or Q344ter rhodopsin shows abnormal accumulation of the Q344ter,
      but not the endogenous rhodopsin, in the plasma membrane of the photoreceptor
      cell body. These data indicate that rhodopsin's carboxy-terminus is required for
      efficient transportation to or retention in the outer segment.

PMID- 7523629
TI  - Sodium/calcium exchange in rat cortical astrocytes.
AB  - Regulation of the cytosolic free Ca2+ concentration ([Ca2+]cyt) by an Na/Ca
      exchanger was studied in primary cultured rat cortical astrocytes. [Ca2+]cyt was
      measured by digital imaging in cells loaded with fura-2. The resting [Ca2+]cyt,
      approximately 150 nM, was only slightly increased by reducing the extracellular
      Na+ concentration ([Na+]o) to 6.2 mM, or by treating the cells with ouabain for
      15 min (to raise cytosolic Na+). Following treatment with ouabain, however,
      lowering [Na+]o caused [Ca2+]cyt to rise rapidly to approximately 1300 nM. When
      Ca2+ sequestration in intracellular stores was blocked by thapsigargin, lowering
      [Na+]o increased [Ca2+]cyt to approximately 1500 nM in the absence of ouabain.
      The low-[Na+]o-stimulated rise in [Ca2+]cyt was abolished by removal of external
      Ca2+, but was not blocked by the Ca2+ channel blocker verapamil, or by caffeine
      or ryanodine, which deplete an intracellular Ca2+ store responsible for Ca(2+)
      induced Ca2+ release. These data suggest that Na+ gradient reduction promotes net
      Ca2+ gain via Na/Ca exchange. Normally, however, a large rise in [Ca2+]cyt is
      prevented by sequestration of the entering Ca2+; this buffering of cytosolic Ca2+
      can be circumvented by blocking sequestration with thapsigargin, or overwhelmed
      by enhancing net Ca2+ gain by pretreating the cells with ouabain. The presence of
      Na/Ca exchanger protein and mRNA in the astrocytes was confirmed by Western and
      Northern blot analyses, respectively. Immunohistochemistry revealed that
      exchanger molecules are distributed in a reticular pattern over the astrocyte
      surface. We suggest that the Na/Ca exchanger plays a role in regulating both
      [Ca2+]cyt and the intracellular stores of Ca2+ in astrocytes, and may thus
      contribute to the control of astrocyte responsiveness to neurotransmitters and
      neurotoxins.

PMID- 7523632
TI  - Axon-glia interactions regulate ECM patterning in the postnatal rat olfactory
      bulb.
AB  - It has been suggested that an inhibitory ECM containing chondroitin-6-sulfate
      proteoglycan (C-6S-PG) and tenascin (TN), which appears homogeneously in the core
      of the OB following afferent fiber arrival, helps position ingrowing olfactory
      axons in the prospective glomerular layer (GL) (Gonzalez and Silver, 1992;
      Gonzalez et al., 1993). Later, a similar ECM associated with astrocytes envelopes
      axonal glomeruli in rings, suggesting that axons may control the precise ECM
      patterning. The question remains whether formation of the matrix ring pattern
      around each axonal glomerulus is an intrinsic property of the matrix-producing
      cells or a response to developing axons. To determine if the organization of
      glial associated matrix in the OB was dependent on the presence of axons, we
      studied the effect of unilateral injection of a neurotoxin into the olfactory
      epithelium of postnatal rats. Using olfactory marker protein (OMP), beta-tubulin
      (TUJ1) antibodies, and Nissl staining, we found that at 5 and 10 d following
      neurotoxin administration the number of glomeruli decreased by an average of
      77.0% in the injected side. At the same time, we observed that the TN/C-6S-PG
      rings and periglomerular cells were present only around the remaining small
      number of glomeruli. Elsewhere, ECM expression and the periglomerular cell
      configuration were more disorganized in the GL. The pattern of glial fibrillary
      acidic protein (GFAP) did not change significantly. We found that OMP staining,
      beta-tubulin immunoreactivity, and periglomerular cells reformed in a glomerular
      like pattern as the olfactory axons reformed by 20 d. As the glomeruli-shaped
      collection of axon terminals reappeared, TN/C-6S-PG immunoreactivity also
      reoccurred in rings around the new axon bundles. Again, at this later stage, the
      expression of GFAP was similar in both sides. In our previous study (Gonzalez et
      al., 1993), we suggested that the initial gross positioning of glomeruli may be
      controlled by the overall positioning of TN/C-6S-PG. In the present study, we
      suggest that the formation of TN/C-6S-PG in the precise ring pattern around
      glomeruli appears to be dependent upon the presence of bundled olfactory axons.
      Various mechanisms are discussed that may explain the dynamic change in ECM
      expression that occurs inside the glomerulus after the neurotoxin treatment.

PMID- 7523633
TI  - IL-2 induces vasopressin release from the hypothalamus and the amygdala: role of
      nitric oxide-mediated signaling.
AB  - The neuropeptide arginine vasopressin (AVP) can replace the cytokine interleukin
      2 (IL-2) as a T-cell mitogen for the induction of interferon gamma (IFN gamma)
      expression in splenic cultures. IL-2-like and IL-2 receptor immunoreactivity have
      been reported in different brain regions, under normal and pathophysiological
      conditions. Regulatory functions for IL-2 in the CNS have been suggested. In
      addition to the spleen, AVP might also mediate some IL-2 effects centrally. In
      the present study, we evaluated the effect of IL-2 on the in vitro release of AVP
      from the hypothalamus and amygdala. In addition, we used these release systems to
      study the possible involvement of NO-mediated signaling in AVP release, based on
      the reported detection of nitric oxide synthase (NOS) in the hypothalamus and
      amygdala. IL-2 rapidly stimulates AVP release in both regions, in a calcium- and
      dose-dependent manner. In addition, nitroprusside also induces AVP release.
      Norepinephrine also induces AVP release from both the hypothalamus, as well as
      the amygdala. The norepinephrine-induced AVP release is antagonized by
      phentolamine, but not by propranolol, suggesting an alpha-adrenergic receptor
      mediated AVP response in both brain regions. The IL-2- and acetylcholine-induced
      AVP release is antagonized by Ng-methyl-L-arginine, indicating a role for NO in
      this AVP release. Ng-methyl-L-arginine does not affect the norepinephrine-induced
      AVP release. A stimulatory effect of IL-2 on hypothalamic CRF release and plasma
      ACTH has already been reported. Our results suggest that in addition to CRF, AVP
      may also mediate the IL-2 stimulation of ACTH secretion. These data further
      suggest that in addition to the hypothalamus, the amygdala may also play a role
      in the bidirectional communication between neuroendocrine and immune systems.
      Understanding the mode of interaction between IL-2 with AVP could clarify the
      pathophysiologic or toxic effects of high brain levels of IL-2.

PMID- 7523631
TI  - Reorganization of neural peptidergic systems in the median eminence after
      hypophysectomy.
AB  - Earlier studies have shown the formation of a novel neural lobe after
      hypophysectomy, an experimental manipulation that causes transection of
      neurohypophyseal nerve fibers and removal of pituitary hormones. The mechanisms
      that underly this regenerative process are poorly understood. The localization
      and number of peptide-immunoreactive (-IR) fibers in the median eminence were
      studied in normal rats and in rats at different times of survival after
      hypophysectomy using indirect immunofluorescence histochemistry. The number of
      vasopressin (VP)-IR fibers increased in the external layer of the median eminence
      in 5 d hypophysectomized rats. Oxytocin (OXY)-IR fibers decreased in the internal
      layer and progressively extended into the external layer. At long survival times
      (9 and 16 months) both VP- and OXY-IR fibers had a bilayered distribution
      occupying both the external and internal layers. Double-labeling experiments
      combining VP and tyrosine hydroxylase antisera as well as OXY and growth hormone
      releasing factor antisera showed that injured neurosecretory fibers growing into
      the external layer displaced fibers from parvocellular cells originally located
      there. As a result, there was essentially an inversion in the distribution of
      these fibers within the median eminence. Galanin (GAL)- and cholecystokinin (CCK)
      IR fibers exhibited a similar pattern of distribution after the lesion. Thus,
      after 5 d there was an increase in GAL- and CCK-IR fibers in the internal layer.
      At 14 and 30 d, the number of GAL- and CCK-IR fibers progressively decreased, but
      after longer survivals (9 and 16 months) there was a dramatic reappearance.
      Dynorphin (DYN)-LI showed a dramatic increase at all levels of the median
      eminence at short survival times after hypophysectomy, followed by a subsequent
      decrease to a final stage of a few, strongly immunoreactive fibers in the
      external layer at longer survival times. Vasoactive intestinal polypeptide (VIP)-
      and peptide histidine-isoleucine (PHI)-IR fibers in hypophysectomized animals had
      already contacted portal vessels 5 d after hypophysectomy, and from then on
      progressively increased in numbers. Finally, most of the peptide fibers described
      above formed dense innervation patterns around the large blood vessels along the
      lateral borders of the median eminence. The present results show that
      hypophysectomy induces a wide variety of changes in hypothalamic neurosecretory
      fibers. Not only is the expression of several peptides in these fibers modified
      following different survival times, but a reorganization of the distribution of
      immunoreactive fibers within the median eminence is demonstrated. The hypothesis
      is raised that regeneration of injured neurosecretory fibers may be dependent on
      changes in the expression of peptides possessing trophic actions.

PMID- 7523634
TI  - Vascular permeability factor in brain metastases: correlation with vasogenic
      brain edema and tumor angiogenesis.
AB  - Metastatic brain tumors are almost always associated with vasogenic brain edema,
      which in turn plays a pivotal role in the evolution of neurological morbidity
      associated with these lesions. Attention has recently focused on a group of
      proteinaceous vascular permeability factors (VPF's) that are capable of inducing
      angiogenesis and promoting increased capillary permeability. To test the
      hypothesis that metastatic brain tumors expressing VPF's are associated with
      peritumoral cerebral edema, a rabbit polyclonal immunoglobulin (Ig) G anti-VPF
      was used to immunostain pathological specimens of metastatic cerebral tumors
      obtained from 22 patients who underwent surgery at Yale-New Haven Hospital.
      Magnetic resonance (MR) imaging was used to correlate VPF staining in tumor
      tissue with the occurrence of peritumoral brain edema. A histological study of
      the microvasculature was then conducted by immunostaining the specimens for
      endothelial cell factor VIII surface antigen, using two gliosis specimens as
      controls. Results revealed 21 of 22 tumors stained positively for VPF's; the
      negative-VPF tumor was a melanoma that exhibited no peritumoral edema. Twenty of
      22 tumors had MR imaging-evident vasogenic edema. The presence and intensity of
      VPF immunostaining of microvascular features were noted and compared. Factor VIII
      staining demonstrated tumor vascularity to be most abundant in VPF-rich regions
      of tumor. The authors therefore report a high correlation between the presence of
      VPF's and the occurrence of peritumoral brain edema associated with cerebral
      metastases.

PMID- 7523630
TI  - Behavioral, biochemical, histological, and electrophysiological effects of 192
      IgG-saporin injections into the basal forebrain of rats.
AB  - The behavioral, biochemical, histological, and electrophysiological effects of a
      basal forebrain injection of saporin, a ribosome-inactivating protein, coupled to
      a monoclonal antibody against the low-affinity NGF receptor (192 IgG) were
      investigated in adult rats. Within the basal forebrain region, the low-affinity
      NGF receptor is exclusively expressed by cholinergic neurons in the medial septal
      area, diagonal band, and nucleus basalis magnocellularis (NBM). The presence of
      this receptor upon these cells confers a degree of specificity to the 192 IgG
      saporin that could not previously be achieved by previous lesioning techniques,
      such as excitatory amino acids. Rats with unilateral injections of different
      amounts of 192 IgG-saporin were prepared to determine the optimal conditions in
      order to produce a lesion restricted to the NBM that would not destroy
      cholinergic afferents to hippocampus or nearby regions. Electroencephalographic
      (EEG) recordings were taken from these lesioned rats before and during treatment
      with scopolamine (1 mg/kg, i.p.). Another group of rats received bilateral NBM
      injections of 192 IgG-saporin and were behaviorally tested using a rewarded,
      delayed-alternation task on a T-maze and a passive avoidance task. Finally,
      histological and biochemical investigations confirmed the effectiveness and
      specificity of the 192 IgG-saporin. The results showed that the 192 IgG-saporin
      did not destroy neurotensin, galanin, somatostatin, NADPH-diaphorase, or
      neuropeptide Y neurons within the NBM. Also, biomarkers of cholinergic function
      were significantly decreased throughout the neocortex and within the NBM, but not
      in the olfactory bulbs, hippocampus, or dorsal caudate nucleus. Intraperitoneal
      injections of scopolamine, but not NBM injections of 192 IgG-saporin, increased
      total power across all frequency bands; however, slow-wave frequencies showed a
      greater increase in power as compared to fast-wave frequencies. Acquisition, and
      performance of the delayed-alternation or passive avoidance tasks were not
      impaired by the lesions. These data confirm the effectiveness and specificity of
      this novel lesioning tool and suggest that selective loss of NBM cholinergic
      cells is not sufficient to impair performance in these behavioral tasks.

PMID- 7523636
TI  - Effect of link protein and free hyaluronic acid binding region on spacing of
      proteoglycans in aggregates.
AB  - Aging of articular cartilage results in accumulation of aggrecan fragments of
      various sizes that retain their ability to aggregate even though they may have
      relatively few glycosaminoglycan chains. Residual binding of partially degraded
      aggrecan may prevent binding of newly synthesized aggrecan subunits that have
      greater numbers of glycosaminoglycan chains. This study was undertaken to
      determine the effects of various relative molar ratios of intact aggrecan, link
      proteins, and hyaluronic acid binding region fragments on the structure of
      reconstituted aggregates. High molar ratios of link proteins relative to aggrecan
      decreased the spacing between adjacent aggrecan subunits; low molar ratios of
      hyaluronic acid binding region relative to aggrecan (4:1 or less) had no
      significant effect on spacing, and high molar ratios resulted in an increase in
      the spacing and a decrease in the percentage of aggrecan subunits found in
      aggregates. These data suggest that the density of aggrecan subunits on the
      aggregate is determined primarily by steric hindrance of the glycosaminoglycan
      chains of the aggrecan subunits and that, to a limited extent, partial
      degradation of aggrecan in an aggregate allows attachment of more aggrecan
      subunits.

PMID- 7523637
TI  - Diagnosis of HIV-1 infection by detection of antibody IgG to HIV-1 in urine with
      ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay)
      using recombinant proteins as antigens.
AB  - Anti-HIV-1 IgG in urine was detected by an ultrasensitive enzyme immunoassay
      (immune complex transfer enzyme immunoassay) using recombinant reverse
      transcriptase (RT), p17 and p24 as antigens, and beta-D-galactosidase from
      Escherichia coli as label. Anti-HIV-1 IgG in urine was reacted simultaneously
      with 2,4-dinitrophenyl-bovine serum albumin-recombinant protein conjugate and
      recombinant protein-beta-D-galactosidase conjugate. The immune complex formed,
      consisting of the three components, was trapped onto polystyrene balls coated
      with affinity-purified (anti-2,4-dinitrophenyl group) IgG. After washing, the
      immune complex was eluted from the polystyrene balls with excess of epsilon N-2,4
      dinitrophenyl-L-lysine and transferred to clean polystyrene balls coated with
      affinity-purified (anti-human IgG gamma-chain) IgG. Finally, the enzyme activity
      bound to the last solid phase was assayed by fluorometry. Using recombinant RT as
      antigen, the sensitivity and specificity for 83 seropositives and 100
      seronegatives were both 100%, and the lowest signal for 60 asymptomatic carriers
      was 8.2-fold higher than the highest signal for the seronegatives. The positivity
      with recombinant RT as antigen could be confirmed by using recombinant p17 and
      p24 as antigens. The sensitivity could be improved by a longer assay of bound
      beta-D-galactosidase activity by using concentrated urine samples and by the
      combined use of recombinant RT, p17, and p24. Thus, reliable diagnosis of HIV-1
      infection was possible for asymptomatic carriers.

PMID- 7523638
TI  - Ectopic production of prostate specific antigen by a breast tumor metastatic to
      the ovary.
AB  - We have recently reported that about 30% of breast tumors produce prostate
      specific antigen (PSA). We examined here, 99 primary ovarian cancer tumors and
      found relatively low levels of PSA in only three tumors. One patient with
      metastatic ovarian cancer from a primary breast tumor, produced relatively high
      levels of PSA and responded well to antiestrogen treatment although she was
      steroid receptor-negative. Another patient with metastatic ovarian cancer from a
      primary breast tumor did not produce PSA and did not respond to treatment
      although she was steroid hormone receptor-positive. This data describe for the
      first time, ectopic PSA production by a breast tumor at the ovarian metastatic
      site and further support the view that PSA is a favourable prognostic indicator
      in breast cancer.

PMID- 7523635
TI  - Quantitative imaging of estrogen and progesterone receptors, estrogen-regulated
      protein, and growth fraction: immunocytochemical assays in 52 meningiomas.
      Correlation with clinical and morphological data.
AB  - Quantitative imaging of estrogen receptors (ER's), progesterone receptors (PR's),
      estrogen-regulated protein (pS2), and growth fraction (Ki67) immunocytochemical
      assays were performed in 52 meningiomas. The results were correlated with
      clinical (age, sex, hormonal status, and tumor volume and location) and
      morphological (histological types and grades) data. The authors observed a lack
      of ER's in all meningiomas but the presence of PR's in 53% of these meningiomas.
      The immunoreactivity was restricted to tumor cell nuclei. The PR
      immunocytochemical assay was correlated with tumor location, histological type,
      histological grade, and pS2 immunocytochemical assay, but not with Ki67
      immunocytochemical assay; high PR content was observed in cisternae,
      transitional, meningothelial, and low-grade meningiomas. Only 11 meningiomas
      showed more than 1% Ki67 immunoreactive nuclei. These meningiomas were usually
      located in the convexity and were of high histological grade. Estrogen-regulated
      protein immunoreactivity was observed in 34 meningiomas but the number of
      immunoreactive nuclei was low. The pS2 immunocytochemical assay was not related
      to clinicopathological features but was preferentially observed in PR-negative
      meningiomas. The results of this study are compared with those previously
      reported, and the function and regulation of PR's in meningiomas is discussed.
      The results indicate that 1) regulation of PR's and pS2 proteins in meningiomas
      differs from regulation in estrogen-dependent tissues such as breast or
      endometrium; 2) interruption of hormonal therapy in women presenting with a
      meningioma is not absolutely necessary; 3) meningiomas have different biological
      properties according to their clinicopathological features; and 4) future studies
      of hormonal clinical trials should be performed on well-defined meningioma
      subgroups.

PMID- 7523639
TI  - Whipple's disease: a histological, immunocytochemical, and electron microscopic
      study of the small intestinal epithelium.
AB  - At endoscopy, the duodenum in Whipple's disease frequently appears abnormal and
      some clinical features such as gastrointestinal blood loss and anaemia suggest
      epithelial damage. However, the intestinal epithelial cells themselves appear to
      be normal on light and electron microscopy. The aims of this study were to
      analyse in detail the cytological changes in epithelial cells over time and in
      response to therapy in biopsies obtained from 20 patients, to investigate the
      functional repercussion on digestive enzymes such as lactase, and to assess the
      expression by the epithelial cells of MHC antigens. Cytological changes were
      minimal at both the light- and the electron-microscopic level and MHC class I
      expression was preserved. However, changes indicative of functional deficits were
      demonstrated. Lactase and MHC class II expression were reduced or even absent.
      Antibiotic therapy resulted in normalization within 3-6 months. These findings
      are consistent with the clinical evolution and are of interest with regard to the
      importance of the immune response in aetiopathogenesis.

PMID- 7523640
TI  - Co-expression of endothelial cell and macrophage antigens in Kaposi's sarcoma
      cells.
AB  - The histopathogenesis of Kaposi's sarcoma (KS) was investigated using
      immunocytochemistry in 12 skin biopsies obtained from two AIDS patients, nine
      patients with the classic form, and one organ-transplant patient. KS cells
      revealed a peculiar antigenic profile, being characterized by co-expression of
      endothelial and macrophage markers. KS cells were stained for von Willebrand
      factor (vWF); for vascular endothelial (VE) cadherin, an endothelial specific
      adhesion molecule; and for PECAM/CD31. In addition, they expressed the macrophage
      antigens PAM-1, CD68, and CD14, and were positive for vitronectin receptor and
      alpha-1,5,6/beta-1 integrins. KS cells were weakly stained for ICAM-1 in 6 of 12
      cases and were negative for VCAM-1 and E-selectin.

PMID- 7523641
TI  - Alterations in the glomerular charge barrier in human lupus nephritis.
AB  - Renal tissue taken from ten patients with proteinuria and diagnosed as suffering
      from human lupus nephritis was examined by a post-embedding charge labelling
      method using cationic gold (CG). The method allows localization of the anionic
      charge in the glomerular epithelial cell coat and/or glomerular basement membrane
      (GBM). Our results demonstrate that in human lupus nephritis there are gaps in
      the charge barrier associated with immune deposits found in the lamina rara
      externa of the GBM. These data suggest that the loss of glomerular fixed anionic
      charges in the GBM may play an important role in the development of proteinuria
      in patients suffering from lupus nephritis.

PMID- 7523642
TI  - Ki-S1 and PCNA expression in erythroid precursors and megakaryocytes--a
      comparative study on proliferative and endoreduplicative activity in reactive and
      neoplastic bone marrow lesions.
AB  - The monoclonal antibody Ki-S1 reacts with a cell proliferation-associated nuclear
      antigen which is expressed in the G1 through G2/M phases of the cell cycle and is
      resistant to formalin fixation. We have studied Ki-S1 and PCNA (PC10)
      immunostaining of erythroid precursors (proliferative activity) and
      megakaryocytes (endoreduplicative activity) in bone marrow trephine biopsies in a
      variety of reactive and neoplastic lesions using double immunohistochemistry to
      identify both cell lineages. A significant increase in Ki-S1 labelling compared
      with PCNA positivity was found in all conditions studied. In particular,
      specimens derived from secondary polycythaemia (SP), polycythaemia vera (P.
      vera), and primary osteomyelofibrosis (OMF), and from splenic tissue with myeloid
      metaplasia (MM), revealed a disproportionally high labelling index of
      erythropoiesis, which was not present in chronic myelogenous leukaemia (CML),
      AIDS, and autoimmune (idiopathic) thrombocytopenia (ITP). Enhancement of Ki-S1
      (PCNA) staining in SP and P. vera is in keeping with the relevant increase in
      erythroid precursor proliferation, but in OMF and MM there is overexpression of
      both proliferation markers, possibly due to secondary folic acid deficiency,
      which is known to cause a block in the S-phase of the cell cycle. A significant
      correlation was observed between the sizes of megakaryocytes and their nuclei
      with Ki-S1 (and also PCNA) staining. Ki-S1 (and PCNA) labelling of predominantly
      smaller elements of this lineage supports a hypothesis that the phases of the
      cell cycle have different durations in the various steps of polyploidization,
      with a prolongation of G1/G2 at higher ploidy levels.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7523644
TI  - Non-enzymatic retrieval of antigen permits staining of follicle centre cells by
      the rabbit polyclonal antibody to protein gene product 9.5.
AB  - The rabbit polyclonal antibody to protein gene product 9.5 (PGP9.5) will detect
      the L1 isoenzyme of ubiquitin carboxy-terminal hydrolase (UCH), which is a marker
      for neurones and neuroendocrine tissue. We re-evaluated this antibody using the
      technique of non-enzymatic antigen retrieval (boiling sections in citrate buffer,
      heated by microwave oven) followed by streptavidin-biotin-peroxidase staining.
      Due to the fortuitous choice of appendix as positive control material containing
      small nerves, we found strong, repeatable cytoplasmic and nuclear staining of
      lymphoid follicle centre cells in addition to neural tissue. This effect could be
      repeated on other lymphoid tissues and was not dependent on microwave heating,
      but did require boiling in an ionic buffer solution. Staining was also observed
      with a fresh batch of antibody and with four of the five different batches of
      antibody which were supplied to us. This pattern was not obtained in fresh
      tissue, in fixed material following trypsinization, or by increasing the primary
      antibody concentration. We suggest that the boiling of sections in citrate buffer
      is exposing an epitope for the anti-PGP9.5 antibody which is inaccessible in the
      native or fixed state and therefore we would recommend retesting of antibody
      specificity following non-enzymatic retrieval of antigen.

PMID- 7523643
TI  - Computer-assisted chromatin texture characterization of Feulgen-stained nuclei in
      a series of 331 transitional bladder cell carcinomas.
AB  - The chromatin patterns of Feulgen-stained nuclei in a series of six specimens of
      normal mucosa and 331 transitional bladder carcinomas, including 293 superficial
      (Ta and T1) and 38 invasive (T2-T4) cases, were quantitatively described by means
      of eight parameters relating to densitometric, run-length distribution, and co
      occurrence matrix features. The results show that the chromatin texture of the
      superficial lesions was markedly different from that of the invasive tumours,
      which exhibited a distinctly more dense and heterogeneous chromatin pattern. The
      data also show that the increasing level of malignancy, as revealed by the
      increasing clinical stage, was accompanied by an increase in the overall
      chromatin condensation level. Only some areas of the nucleus actually increased
      in density; other pale areas appeared concomitantly with these increasingly
      denser chromatin areas. This chromatin density increase corresponded to a marked
      increase in the frequency of small dense chromatin clumps; these joined together
      into very large dense chromatin clumps, which were distributed more and more
      heterogeneously in the nucleus as the clinical stage of the tumour increased.

PMID- 7523645
TI  - An in vitro model of urothelial regeneration: effects of growth factors and
      extracellular matrix proteins.
AB  - Although the cellular turnover of resting urothelium is very low, its
      regenerative capacity is known to be outstanding. In organotypic mouse urothelial
      cultures closely mimicking the differentiation and multilayering of normal
      urothelium, we examined the cell biological mechanisms underlying urothelial
      regeneration and the specific role of growth factors and several extracellular
      matrix (ECM) components. Exposure to epidermal growth factor (EGF) and acidic
      fibroblast growth factor (aFGF) and culture on laminin resulted in enhanced
      expansion of the urothelium. Microscopy and assessment of proliferative activity
      revealed that enhanced urothelial expansion due to EGF could be attributed to
      increased proliferative activity and an increase in cell numbers, whereas aFGF
      stimulated expansion must be considered the consequence of increased cellularity
      and migration. Laminin-enhanced urothelial expansion was shown to be the result
      of spreading of the entire urothelial organotypic culture. This was associated
      with a considerable decrease in the number of cell layers. A synergistic effect
      of growth factors and laminin was not found. This organotypic urothelial cell
      culture model seems to be very useful in studying strategies to improve
      urothelial regeneration.

PMID- 7523646
TI  - Induction of nitric oxide synthase in the neo-vasculature of experimental tumours
      in mice.

PMID- 7523647
TI  - Prevention of iron deficiency and psychomotor decline in high-risk infants
      through use of iron-fortified infant formula: a randomized clinical trial.
AB  - OBJECTIVE: To determine the efficacy of iron-fortified infant formula in
      preventing developmental delays and abnormal behavior. DESIGN: Double-blind,
      randomized, controlled trial. SETTING: Urban hospital clinic. PARTICIPANTS: A
      total of 283 healthy, bottle-fed infants from very low income families. Children
      with prematurity, low birth weight, and major anomalies and those who had
      received more than 2 weeks of evaporated-milk feedings were excluded. The groups
      were similar for sociodemographic background variables. Fifty-eight infants
      (20.5%) dropped out before any outcome data were gathered; 225, 204, 186, and 154
      remained at 6-, 9-, 12-, and 15-month assessments, respectively. INTERVENTION:
      Iron-fortified formula (12.8 mg iron per liter) versus regular formula (1.1 mg
      iron per liter). MAIN OUTCOME MEASURES: Iron status was measured on venous blood
      by determination of hemoglobin, serum iron and iron-binding capacity, serum
      ferritin, and free erythrocyte protoporphyrin values. The Bayley Scales of Infant
      Development (mental and psychomotor indexes) and two factors of the Infant
      Behavior Record (test affect and task orientation) were the outcomes of interest.
      RESULTS: All measures of iron status were significantly different between groups
      (p < 0.001). Psychomotor development patterns differed between groups (F3,520,
      3.4; p = 0.02) with time. Mean values were similar at 6 months but differed at 9
      and 12 months of age (p < 0.001), with a decline of 6.4 points in the regular
      formula group. By 15 months of age the differences were no longer significant (p
      = 0.23). Mental development and behavior were not affected. CONCLUSIONS: Iron
      fortified formula significantly reduced iron deficiency in a high-risk group of
      infants and prevented a decline in psychomotor development quotients. This effect
      may be transient, and its long-term significance needs further study.

PMID- 7523648
TI  - Iron deficiency and infant development.

PMID- 7523649
TI  - Disturbances in growth hormone secretion and action in adolescents with anorexia
      nervosa.
AB  - Women in whom anorexia nervosa develops during adolescence have failure of linear
      growth associated with low levels of insulin-like growth factor I (IGF-1). To
      investigate the pathophysiology of growth retardation in adolescents with
      anorexia nervosa, we measured basal growth hormone (GH), growth hormone-binding
      protein (GHBP), IGF-1, and insulin-like growth factor binding protein-3 (IGFBP-3)
      in three groups of patients: (1) 28 recently hospitalized female adolescents with
      anorexia nervosa, (2) 23 of the same patients after partial weight restoration,
      and (3) 28 healthy control subjects matched for age, sex, and pubertal stage.
      Fasting GH levels in group 1 did not differ significantly from those in group 3.
      In contrast, serum GHBP (p < 0.001), IGF-1 (p < 0.001), and IGFBP-3 (p < 0.01)
      were significantly lower in group 1 than in group 3. Serum GHBP and IGFBP-3
      levels were positively correlated with body mass index. Serum GHBP levels were
      low in patients in all five pubertal stages and even in those shown to have
      adequate GH secretion. In group 2 (after refeeding) the serum IGF-1 concentration
      increased significantly and GHBP and IGFBP-3 returned to normal. We conclude that
      patients with anorexia nervosa have diminished GH action resulting in decreased
      secretion of IGF-1. The positive correlation with body mass index and the
      reversibility with refeeding suggest that these changes are secondary to
      malnutrition. Altered GH function that occurs during the years of active growth
      can explain the growth retardation seen in anorexia nervosa.

PMID- 7523650
TI  - Detection of Fasciola hepatica in infected intermediate hosts using RT-PCR.
AB  - Fasciola hepatica, the common bile duct fluke, is an economically important
      parasite of domestic livestock. Current research interest is directed toward an
      understanding of the parasite's biology at the intermediate host level. To permit
      study of seasonal transmission patterns and parasite/intermediate host
      interactions, a fasciolid-specific assay has been developed to detect infected
      snail vectors. This assay uses the reverse transcriptase-polymerase chain
      reaction (RT-PCR) to amplify specifically a region of F. hepatica small-subunit
      rRNA, followed by hybridization to an F. hepatica-specific probe. The assay does
      not cross-react with 2 trematodes outside of the Fasciolidae but does detect
      Fascioloides magna rRNA. Sequence alignment with additional small-subunit rRNAs
      shows Fasciolopsis buski would also cross-react with the assay. The detection
      limit of the assay is 10 fg of fluke total RNA with 5 micrograms of snail RNA
      added as background. Additionally, the assay detects individual infected snails
      immediately after miracidial exposure and throughout the parasite's development
      period.

PMID- 7523651
TI  - Screening of trisomy 21.

PMID- 7523652
TI  - Cardiac response to autonomic drugs in atria of diabetic mouse.
AB  - Comparisons of chronotropic effects of sympathomimetic and parasympathomimetic
      agents were made in isolated atria from alloxan-induced diabetic and age-matched
      control mice. In atria from mice rendered diabetic for three months, the cardiac
      response to bethanechol was potentiated compared with that of the age-matched
      control atria. However, the cardiac responses of atria from alloxan-treated mice
      to noradrenaline, 3-isobutyl-1-methyl-xanthine and 1,1-dimethyl-4-phenyl
      piperazinium iodide were similar to those of the controls.

PMID- 7523655
TI  - Inhibition of nitric oxide synthase prevents myocardial protection by ramiprilat.
AB  - The objective of this investigation was to determine the role of nitric oxide
      synthase in the action of the angiotensin-converting enzyme inhibitor,
      ramiprilat, to reduce myocardial ischemia/reperfusion injury. Ramiprilat, the
      nitric oxide synthase inhibitor NG-nitro-L-NAME (L-NAME), ramiprilat plus L-NAME,
      or saline (n = 8 each group), were administered i.v. in intact animal
      preparations of experimentally induced acute myocardial ischemia. Anesthetized,
      open-chest rabbits were instrumented for measurement of systemic hemodynamics and
      left ventricular pressure from which left ventricular +dP/dtmax was derived.
      Animals were subjected to 30 min of left main coronary artery occlusion (marginal
      branch) followed by 2 hr of reperfusion. Ramiprilat (50 micrograms/kg) or saline
      was administered 5 min before reperfusion, and those rabbits receiving L-NAME
      (100 micrograms/kg/min) were pretreated starting 30 min before occlusion
      throughout the remainder of the experiment. After reperfusion, myocardial infarct
      size (IS) was determined via tetrazolium staining and expressed as a percentage
      of area at risk (AR). IS/AR% was significantly reduced in rabbits administered
      ramiprilat (19 +/- 3%) compared to those receiving saline (39 +/- 2%), ramiprilat
      plus L-NAME (43 +/- 4%) or L-NAME alone (43 +/- 2%; mean +/- S.E.M.; P < .05). AR
      as a percent of total left ventricular mass was not different between any of the
      four treatment groups. Systemic hemodynamic effects were not significantly
      different between groups. The results indicate that the effect of ramiprilat to
      reduce infarct size is abolished by pretreatment with L-NAME.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7523653
TI  - Preferential antibody recognition of structurally distinct HIV-1 gp120 molecules.
AB  - We have developed an assay, using a biosensor matrix and surface plasmon
      resonance, that rapidly and reproducibly measures antibody reactivity to human
      immunodeficiency virus type 1 (HIV-1) gp120 in various structural conformations.
      In particular, antibodies displaying preferential reactivity to a CD4-binding
      competent ("native," rgp120) or CD4-binding incompetent ("reduced," rcmgp120)
      monomeric gp120 molecule were distinguished. This technique has advantages over
      conventional enzyme-linked immunosorbent assay (ELISA) methodology in which it is
      difficult to control the concentration of protein adsorbed to the ELISA wells and
      a significant disruption of protein structure occurs on adsorption. A population
      of gp120 molecules that lacked CD4 receptor binding capacity and bound antibodies
      specific for reduced gp120 was found in several native gp120 preparations. The
      relative amount of this CD4-binding incompetent population varied among the
      various preparations studied. This presence of CD4-binding incompetent molecules
      within various native recombinant gp120 preparations may have implications for
      HIV-1 envelope vaccine development. By measuring antibody-binding ratios, several
      monoclonal antibodies were identified, which, although elicited by immunization
      with various native gp120 preparations, bound specifically to reduced gp120. The
      ability to screen antibody specificity against HIV-1 envelope proteins with
      different conformations will assist in determining the quality of antibodies
      induced by various HIV-1 envelope vaccine candidates.

PMID- 7523656
TI  - Nitric oxide as a mediator of bisacodyl and phenolphthalein laxative action:
      induction of nitric oxide synthase.
AB  - Bisacodyl and phenolphthalein are diphenylmethane laxatives that have effects on
      intestinal water and electrolyte transport and smooth muscle contractility.
      Nitric oxide (NO) is produced in the intestine, where it stimulates electrolyte
      secretion and relaxes smooth muscle. Therefore, we studied in rats the effect of
      these laxatives on diarrhea, fluid transport in vivo, gastrointestinal transit
      and NO synthase activity in the absence and presence of inhibitors of NO
      synthesis. Both laxatives (50 mg/kg p.o.) produced diarrhea, which was delayed in
      onset by 25 mg/kg (i.p.) of the NO synthase inhibitor NG-nitro-L-arginine methyl
      ester (L-NAME). The L-NAME effect was reversed by the NO donor isosorbide-5
      mononitrate (30-120 mg/kg i.p.). L-Arginine (600 and 1500 mg/kg i.p.) prevented
      the inhibitory effect of L-NAME on diarrhea. The laxatives evoked water and
      electrolyte secretion and enhanced the transit of a suspension of charcoal
      through the gastrointestinal tract. This was inhibited by L-NAME but not D-NAME.
      The inhibitor of inducible NO synthase, dexamethasone (0.03-0.3 mg/kg i.p.),
      prevented the effects of both laxatives on electrolyte and water transport.
      Stimulation by these drugs of NO synthase was also inhibited by dexamethasone.
      The results demonstrate that bisacodyl and phenolphthalein stimulate water and
      electrolyte secretion, promote transit of intraluminal contents and produce
      diarrhea in association with enhanced production of NO. Furthermore, it appears
      that the NO is derived principally from activation of an inducible form of NO
      synthase.

PMID- 7523654
TI  - Lindane increases intracellular calcium in rat myometrial smooth muscle cells
      through modulation of inositol 1,4,5-trisphosphate-sensitive stores.
AB  - Lindane (gamma-hexachlorocyclohexane) is an organochlorine pesticide that
      increases intracellular free calcium ([Ca++]i) in several tissues. Calcium
      homeostasis is central to the excitation and relaxation of uterine muscle during
      labor. The present study, therefore, investigated whether lindane exposure
      modulated [Ca++]i in myometrial smooth muscle cells. This study demonstrated that
      lindane, but not beta-hexachlorocyclohexane, increased [Ca++]i in a concentration
      dependent manner in individual rat myometrial cells, as measured with the calcium
      sensitive probe fura-2-AM. The lindane-induced Ca++ response was rapid in onset
      and protracted in duration. The lindane response was apparently independent of
      external calcium because equivalent [Ca++]i responses were observed in cells
      exposed to lindane in Ca(++)-containing and Ca(++)-free media and in the presence
      of 10 microM nifedipine, a dihydropyridine blocker of plasma membrane voltage
      sensitive Ca++ channels. Prior depletion of internal Ca++ stores that contained
      Ca(++)-induced Ca(++)-release channels by 10 mM caffeine and 1 microM ryanodine
      did not affect lindane's ability to increase [Ca++]i, whereas pretreatment with
      either 1 microM ionomycin or 5 microM carbachol eliminated the lindane-induced
      [Ca++]i increase. These experiments suggest that lindane increases [Ca++]i
      through the selective release of inositol 1,4,5-trisphosphate-sensitive Ca++
      stores. In addition, in Ca(++)-containing buffer, low concentrations of lindane
      (1 microM) rapidly inhibited the regenerative calcium oscillations induced by
      carbachol. If the mechanism is similar in vivo, lindane exposure may perturb many
      finely regulated Ca(++)-dependent processes required for excitation-contraction
      coupling in successful parturition and, therefore, increase the probability of
      delayed or dysfunctional labor.

PMID- 7523658
TI  - Use of selective antagonists for further characterization of tachykinin NK-2, NK
      1 and possible "septide-selective" receptors in guinea pig bronchus.
AB  - NK-1 and NK-2 tachykinin receptors in guinea pig airways appear to have some
      unusual characteristics. The analog [pGlu6,Pro9] SP(6-11) (septide) may also act
      on atypical NK-1 receptors in guinea pig ileum. In this study, we used new
      tachykinin antagonists to investigate further the receptors in the guinea pig
      bronchus. In the presence of 1 microM indomethacin and phosphoramidon, the
      selective agonists [Sar9,Met(O2)11]-SP and [Pro9]-SP (both NK-1),
      [Lys5,MeLeu9,Nle10]-NKA(4-10) (NK-2) and septide were full agonists, with pD2
      values of 8.00, 7.78, 9.11 and 8.52, respectively on epithelium-intact
      preparations. Contractions to septide were unaffected by atropine (5 microM) and
      tetrodotoxin (1 microM). Denudation of epithelium significantly enhanced the
      potency of [Sar9,Met(O2)11]-SP and [Pro9]-SP but not of septide and
      [Lys5,MeLeu9,Nle10]-NKA(4-10). The potency order for NK-2-selective antagonists
      against [Lys5,MeLeu9,Nle10]-NKA(4-10) was GR 94800 > SR 48968 MDL 29913 > MEN
      10207 (pA2 values 8.97, 8.73, 7.11 and 6.49, respectively). The NK-1 selective
      antagonists, OP 96345, GR 82334 and RP 67580 were weak or ineffective against
      [Sar9,Met(O2)11]-SP and [Pro9]-SP (pA2 6.69 or less), whereas they were more than
      one order of magnitude more potent against septide (pA2, 7.78, 7.48 and 6.58,
      respectively). In epithelium-denuded bronchi, the antagonist potency of GR 82334
      was unchanged. These data indicate that septide interacts with tachykinin
      receptors in guinea pig bronchial smooth muscle in a manner different from that
      of [Sar9,Met(O2)11]-SP and [Pro9]-SP, and provide some evidence for heterogeneity
      of NK-1 receptors in the guinea pig airways.

PMID- 7523657
TI  - Pharmacological characterization of LY293284: A 5-HT1A receptor agonist with high
      potency and selectivity.
AB  - (-)-LY293284, (-)-4R-6-acetyl-4-(di-n-propylamino)1,3,4,5-
      tetrahydrobenz[c,d]indole, is a conformationally restricted tryptamine derivative
      with an acetyl group serving as a protophilic substitution for the hydroxyl in
      serotonin (5-HT). In ligand displacement studies, LY293284 had a Ki of 0.07 nM
      for the 5-HT1A receptor but no affinity for other monoaminergic receptors within
      3 orders of magnitude. LY293284 was evaluated in in vivo models, which have been
      used as markers for presynaptic and postsynaptic 5-HT1A receptor activity.
      LY293284 decreased hypothalamic 5-hydroxyindoleacetic acid levels (ED50, 2.9
      micrograms/kg s.c.) and dorsal raphe serotonergic neuron firing rate (ED50, 0.08
      micrograms/kg s.c.), which are accepted indices of presynaptic activity. LY293284
      also induced a reduction in body temperature in rats (ED50, 3.6 micrograms/kg
      s.c.), which was blocked by pretreatment with (+/-)-pindolol. Hypothermic
      responses of rats to 5-HT1A agonists have had both pre- and postsynaptic
      characteristics in previous studies. The ED50 values for 8-hydroxy-2-(di-n
      propylamino)-tetralin (8-OH-DPAT) in these tests were 15 to 45 times higher than
      those observed for LY293284. In models for postsynaptic activity, the ED50 for
      LY293284 for elevating serum corticosterone levels was 9.7 micrograms/kg s.c. and
      the minimum effective doses to induce lower lip retraction and flat posture were
      3 micrograms/kg s.c. For comparison, the same indices obtained for 8-OH-DPAT were
      222.4 and 100 micrograms/kg, respectively. The 5-HT syndrome responses induced by
      LY293284 were also attenuated by pretreatment with (+/-)-pindolol. LY293284 was
      10 times more potent than 8-OH-DPAT in a drug discrimination test that used
      pigeons trained to identify 8-OH-DPAT. In sexual behavior tests with male rats,
      LY293284 induced a maximal reduction in ejaculatory latency at 0.01 micrograms/kg
      s.c., which was approximately 10 times higher potency than 8-OH-DPAT. In the
      pigeon conflict model for anxiolytic activity, LY293284 was 100 times more potent
      than 8-OH-DPAT in increasing punished responding. In the rat forced swim model
      for antidepressant-like activity, LY293284 was 30 and 35 times more potent than 8
      OH-DPAT in decreasing immobility time and defecation rate. These studies have
      demonstrated that LY293284 is a highly selective and extremely potent 5-HT1A
      receptor agonist and represents a useful pharmacological tool for studying 5-HT1A
      receptor-mediated effects.

PMID- 7523659
TI  - Effect of anisotonic conditions on the transport of hydrophilic model compounds
      across monolayers of human colonic cell lines.
AB  - The effect of anisotonic solutions on the enhancement of the transport of
      hydrophilic model compounds across monolayers of Caco-2 and HT-29.cl19A
      intestinal epithelial cells was studied. In filter-grown monolayers of the highly
      differentiated villus-like Caco-2 cell line, a profound and dose-dependent drop
      in the transepithelial electrical resistance was found after apical treatment
      with a 30 or a 50% hypotonic solution (200 and 150 mOsmol, respectively). This
      drop was not observed after basolateral and two-sided application of a 50%
      hypotonic solution. During apical hypotonic treatment a 12- and 8-fold increase
      also was observed in transepithelial transport of two hydrophilic model
      compounds, i.e., fluorescein-Na and fluorescein-isothiocyanate-labeled dextran,
      MW 4000, respectively. Through confocal laser scanning microscopy, it was
      revealed that this enhanced transport was predominantly via the paracellular
      route. Moreover, morphological changes in the cell layers indicating cell
      swelling were observed after apical hypotonic, but not after basolateral or
      bilateral treatment, probably resulting from an incomplete regulatory volume
      decrease response. This swelling, and slight lateral retraction of the cells,
      allowed the hydrophilic compounds to pass between the cells. The effects of
      hypotonic challenge also were studied in monolayers of the more crypt cell-like
      HT-29.cl19A cell line. After apical hypotonic shock, these cells showed no effect
      on transepithelial electrical resistance, whereas an increase was observed after
      basolateral and bilateral treatment. Hypotonic shock failed to increase the
      transport of the hydrophilic model compounds in this cell line.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7523660
TI  - Calcium channel subtypes in cat chromaffin cells.
AB  - 1. Using the patch-clamp technique we have investigated the kinetic and
      pharmacological properties of high-voltage-activated (HVA) Ca2+ channels in short
      term-cultured cat chromaffin cells. 2. In 10 mM Ba2+, HVA currents activated
      around -40 mV, reached maximal amplitude at 0 mV and reversed at about +60 mV. At
      0 mV, HVA current activation was fast (mean tau act, 2.45 ms), and followed by
      either an incomplete inactivation or by a second slow phase of activation (mean
      tau slow, 36.8 ms) that was lost when Ba2+ was replaced by Ca2+. HVA Ba2+
      currents deactivate quickly on repolarization to -50 mV (mean tau deact, 0.36
      ms). 3. In most cells, HVA currents were sensitive to common dihydropyridine
      (DHP) derivatives. Nisoldipine blocked the currents maximally at low membrane
      potentials (mean block 76% at -30 mV, 3 microM) and gradually less at higher
      voltages. Nisoldipine block was clearly time dependent (33 and 56% after 30 and
      600 ms, respectively, to 0 mV). 4. Bay K 8644 (3 microM) action was variable and
      caused (1) a 2- to 4-fold increase of Ba2+ currents at -40 to -20 mV, (2) a -15
      mV shift of the current-voltage relationship and (3) a 10- to 20-fold
      prolongation of HVA channel deactivation at -50 mV. 5. Nisoldipine block and Bay
      K 8644 potentiation of HVA currents increased markedly in omega-conotoxin GVIA
      (omega-CgTX)-pretreated cells, suggesting an increased fraction of DHP-sensitive
      currents in these cells. Nisoldipine block of residual omega-CgTX-resistant
      currents was almost complete (mean block, 82%) during pulses of 1 s to 0 mV. 6.
      The degree of inhibition produced by omega-CgTX (2 microM for 1 min) varied from
      cell to cell (mean block, 46%) and was partly reversible. Residual omega-CgTX
      resistant currents exhibited faster activation-deactivation kinetics than control
      currents. 7. The slow phase of HVA current activation was abolished if a
      conditioning prepulse of 40 ms to +70 mV preceded a test pulse to 0 mV. Double
      pulse protocols caused an average current increase (facilitation) of 37% that was
      voltage dependent and which correlated with the slow phase of Ca2+ channel
      activation. Facilitation was lost in most omega-CgTX-treated cells and was little
      affected by nisoldipine (3 microM) and Bay K 8644 (1 microM). Facilitation was
      potentiated in cells dialysed with 100 microM guanosine 5'-O-(3-thiotriphosphate)
      (GTP-gamma-S) and fully prevented by 1 mM guanosine 5'-O-(2-thiodiphosphate) (GDP
      beta-S).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523661
TI  - Functional role of bicarbonate in propionate transport across guinea-pig isolated
      caecum and proximal colon.
AB  - 1. Unidirectional fluxes of propionate across isolated epithelia from the guinea
      pig caecum and proximal colon were measured under short-circuit current
      conditions. In the caecum and proximal colon the serosal-to-mucosal propionate
      flux (JPrsm) was higher than mucosal-to-serosal flux (JPrms), resulting in a net
      secretory flux of propionate. 2. HCO3(-)-CO2-free solution reduced JPrms in the
      caecum and proximal colon markedly; JPrsm was not (caecum) or little (proximal
      colon) affected. The subsequent addition of acetazolamide caused a further
      decrease in JPrms in the proximal colon, but not in the caecum. 3. In HCO3(-)
      containing solutions acetazolamide or ethoxzolamide inhibited JPrms; JPrsm was
      not affected. A macromolecular carbonic anhydrase inhibitor, prontosil-dextran,
      had no effect on propionate fluxes, indicating that the intracellular carbonic
      anhydrase is of importance for short-chain fatty acid transport. 4. Subsequent to
      carbonic anhydrase inhibition, mucosal addition of amiloride caused a slight
      further decrease of JPrms in the caecum and proximal colon; JPrsm was not
      affected. 5. Results support the view that a considerable proportion of short
      chain fatty acids (SCFAs) is absorbed via a SCFA(-)-HCO3- exchange.

PMID- 7523662
TI  - Potentiation by ATP of the postsynaptic acetylcholine response at developing
      neuromuscular synapses in Xenopus cell cultures.
AB  - 1. Extracellular application of ATP to developing Xenopus neuromuscular synapses
      in culture resulted in a marked increase in the amplitude and frequency of
      spontaneous synaptic currents, using whole-cell recording. 2. The postsynaptic
      action of ATP was examined by studying the response of isolated muscle cells to
      iontophoretically applied acetylcholine (ACh). ATP enhanced the responses of the
      muscle membrane to ACh. The order of potency for various nucleotides (ATP = ADP
      >> AMP, adenosine, GTP) suggests that ATP acts through P2-purinoceptors. The
      effect of ATP on whole-cell currents was also abolished by the protein kinase
      inhibitor H-7. 3. Single-channel measurements indicate that ATP increased the
      mean open time of low-conductance ACh channels. No change in the conductance of
      ACh channels was observed. 4. Local application of ATP to one region of the
      elongated myocyte surface resulted in potentiated ACh responses only at the ATP
      treated region, suggesting that the cytosolic second messengers were effectively
      confined within the muscle cytoplasm. 5. The results of the present study suggest
      that ATP released from the nerve terminals may potentiate the ACh response of
      developing muscle cells during the early phase of synaptogenesis, and that the
      action of ATP can be restricted to the subsynaptic region exposed to the secreted
      ATP.

PMID- 7523663
TI  - VCAM-1 and ICAM-1 are expressed by Langerhans cells, macrophages and endothelial
      cells in oral lichen planus.
AB  - Expression of intercellular adhesion molecule-1 (ICAM-1, CD54) and vascular cell
      adhesion molecule-1 (VCAM-1, CD106) was examined in oral lichen planus (OLP) and
      normal oral mucosa (NOM). Immunoperoxidase staining showed ICAM-1 expression by
      vascular endothelium in all biopsies of OLP and NOM whereas endothelial VCAM-1
      staining was found in 2/7 NOM and 8/9 OLP. In the lamina propria of NOM
      occasional cells were ICAM-1 or VCAM-1 positive, and virtually no staining of
      intraepithelial dendritic cells was seen for either marker. Intraepithelial
      dendritic cells stained for ICAM-1 in 7/9 and VCAM-1 in 4/9 OLP biopsies. Double
      immunofluorescence showed dual labelling of Langerhans cells (LC) with CD1a and
      VCAM-1 in a further 5/12 cases of OLP, but there was no such staining in four
      NOM. This is the first report of LC staining with VCAM-1. Induction of ICAM-1 and
      VCAM-1 on LC and macrophages in OLP suggests these cells are activated and may
      contribute to the pathogenesis of OLP by presenting antigen to infiltrating
      lymphocytes.

PMID- 7523666
TI  - Nitric oxide--from mediator to medicines.
AB  - Nitric oxide is involved in a wide range of physiological processes in humans and
      in animals. It controls vascular tone, acts as a neurotransmitter and
      neuromodulator in the central and peripheral nervous systems and influences the
      activity of the immune system. Substances that selectively enhance or inhibit its
      synthesis or removal and modify its effects, are likely to yield interesting
      therapeutic agents.

PMID- 7523665
TI  - Phenotypic characterisation of stellate and giant cells in giant cell fibroma by
      immunocytochemistry.
AB  - The origin of the stromal, stellate and multinucleate cells in oral giant cell
      fibroma is unclear. Sixteen giant cell fibromas were stained immunocytochemically
      for keratin (MNF 116), vimentin, S-100 protein, neurofilaments, glial fibrillary
      acidic protein, alpha-smooth muscle actin, desmin, CD31 (PECAM-1), CD68, Factor
      XIIIa and prolyl 4-hydroxylase (5B5). In all cases positive staining was found
      with vimentin and prolyl 4-hydroxylase, indicating a functional fibroblast
      phenotype. Reactivity for Factor XIIIa was seen in two cases and in only one was
      a small number of giant cells stained, suggesting that the majority of oral giant
      cell fibromas are unrelated to the histologically similar fibrous papule of the
      nose or facial angiofibroma.

PMID- 7523667
TI  - Characterization of antigenicity and immunogenicity patterns of native and
      recombinant zona pellucida proteins in the white-tailed deer (Oidocoileus
      virginianus).
AB  - The effectiveness of zona pellucida antigens in immunizing white-tailed deer to
      reduce fertility was evaluated by analysing the constituent deer zona pellucida
      proteins and their immunogenicity. Does were immunized with porcine zona
      pellucida antigens. The antibodies were characterized using immunohistochemical
      and immunoblot analysis, in which zona pellucida proteins were separated by one
      dimensional and two-dimensional PAGE. Deer anti-porcine zona pellucida antibodies
      were found to recognize all the major proteins of the porcine zona pellucida.
      These antibodies also recognized several proteins of deer zona pellucida,
      indicating that it is possible to break immune tolerance in the deer using such a
      protocol. The antibodies were also found to recognize peptides of 55 and 75 kDa
      that were produced by expressing cDNA clones containing antigens of major
      glycoproteins of rabbit zona pellucida. Furthermore, antibodies against rabbit
      zonae pellucidae recognized antigens in zonae of paraffin-embedded deer ovaries.
      Taken together, these experiments demonstrate the crossreactive nature of a
      number of zona pellucida epitopes found in deer and in several other species.
      They also illustrate the immunogenicity possible in such an immunization
      protocol, and provide valuable probes for the investigation of follicular
      development in this and other species.

PMID- 7523668
TI  - Immunoreactive substance P and neurokinin A in the hypothalamus and anterior
      pituitary gland of Siberian and Syrian hamsters and of rats.
AB  - In this investigation the concentrations of immunoreactive substance P and
      neurokinin A in the hypothalamus and anterior pituitary of the Siberian hamster
      were compared with those in the rat and Syrian hamster. The concentrations of
      immunoreactive neurokinin A in the hypothalamus of Siberian hamsters were
      significantly higher than those of rats and Syrian hamsters, while male Siberian
      hamsters had similar amounts of substance P in the hypothalamus to those of male
      Syrian hamsters, but had higher amounts than those in male rats. However, female
      Siberian hamsters and significantly higher hypothalamic concentrations of both
      substance P and neurokinin A than did female Syrian hamsters and rats. In the
      anterior pituitary glands of Siberian hamsters, concentrations of substance P and
      neurokinin A were markedly higher than they were in rats and even more so more in
      Syrian hamsters. Ovariectomy further increased tachykinin concentrations in the
      anterior pituitary gland of female Siberian hamsters, and this was completely
      prevented by oestradiol replacement. Female Siberian hamsters kept under
      conditions of reduced photoperiod had significantly higher tachykinin
      concentrations in the anterior pituitary than did animals kept under daily
      photoperiods of 16 h light:8 h dark. The incubation of anterior pituitaries from
      female Siberian hamsters with a neurokinin A receptor antagonist resulted in a
      partial blockade of the LH and FSH release in response to LHRH. Thus, the high
      concentration of tachykinins present in the anterior pituitary of the Siberian
      hamster may have a local role in modulating the secretion or release of
      gonadotrophins.

PMID- 7523664
TI  - Oro-dental self-mutilation in familial dysautonomia.
AB  - Orodental self-mutilation (ODSM) has not gained sufficient recognition in
      familial dysautonomia (FD). Among 38 patients with FD, ODSM was found in 14
      (36.8%). ODSM may be due to peripheral neuropathy with insensibility to pain,
      which is characteristic of FD. Elimination of the sharp edges of teeth was found
      to be helpful.

PMID- 7523669
TI  - A murine monoclonal antibody (RV3-27) raised against isolated human placental
      endogenous retroviral particles and reactive with syncytiotrophoblast.
AB  - Particles with the characteristic shape of enveloped retroviral particles and
      maximal specific reverse transcriptase (RTase) activity at buoyant density of
      1.15-1.17 g/ml have been isolated from human first-trimester chorionic villous
      tissue. Murine monoclonal antibodies (mAbs) to these isolated particles were
      generated. One IgM mAb (RV3-27) showed granular staining of cytoplasmic
      structures within syncytiotrophoblast by immunohistochemistry. Immunoelectron
      microscopic studies have demonstrated focal localisation to small submembranous
      regions of syncytiotrophoblast, as well as reaction with detergent-disrupted
      isolated placental retroviral-like particles. The RV3-27 mAb did not stain other
      human tissues in this focal manner, although increased generalised cytoplasmic
      staining was not uncommon; also, this mAb did not react strongly with the surface
      or cytoplasm of a variety of human cell lines (including choriocarcinoma cells).
      Immunoblotting and HPLC analyses have indicated the reactive placental antigen to
      be a 17-25 kDa protein. It is suggested that the RV3-27 mAb may be reactive with
      a syncytiotrophoblast antigen encoded by an endogenous retroviral sequence.

PMID- 7523670
TI  - Interferon gamma induced production of indoleamine 2,3 dioxygenase in cultured
      human synovial cells.
AB  - OBJECTIVE: Synovial membrane cells from inflamed joints share morphological and
      functional properties with malignant mesenchymal cells. Interferon gamma (IFN
      gamma) has antitumor cell activity related to stimulation of 2,3 indoleamine
      dioxygenase (IDO), a widely distributed tryptophan catabolizing enzyme. Our
      objective was to measure synoviocyte IDO production to determine if the varied
      clinical and in vitro effects of IFN-gamma on nonmalignant immunocompetent cells
      might involve a similar mechanism. METHODS: Using an established radioenzymatic
      assay, we measured IDO activity in suspensions of freshly isolated cells obtained
      by enzymatic dispersion of human synovial membrane, and in fresh and longterm (>
      or = 2 months) cultures of these cells in response to varying concentrations of
      recombinant human interferons alpha 2a, beta ser, or gamma. RESULTS: In fresh and
      in > or = 2 month-old cultures, IFN-gamma strongly stimulated IDO activity, a
      corresponding fall in supernatant tryptophan levels, and an elevation in the
      supernatant concentration of kynurenine, tryptophan's principal metabolite, mRNA
      for IDO was likewise markedly increased in cells after 4 days' incubation with
      IFN-gamma. Staining studies indicated that the IDO producing cells in synovium
      were not typical macrophages. Interferon beta ser had weak IDO stimulatory
      activity that was in a few cases additive to that of IFN-gamma. In no case did
      interferon beta ser abrogate IFN-gamma induced IDO activity increases. Interferon
      alpha 2a also had weak stimulatory activity. CONCLUSIONS: IFN-gamma stimulates
      IDO production and tryptophan metabolism in cultured human synovial cells, and
      therefore may contribute to this cytokine's in vitro and clinical effects in
      arthritis and inflammation.

PMID- 7523671
TI  - Autoimmune sera react with multiple epitopes on recombinant 52 and 60 kDa Ro(SSA)
      proteins.
AB  - OBJECTIVE: To determine the reactivity of recombinant 52 and 60 kDa Ro(SSA) (Ro)
      proteins with sera from 3 subsets of patients with Ro autoantibody associated
      disease. METHODS: Complementary DNA (cDNA) clones that encode the human 52 and 60
      kDa Ro autoantigens were isolated by the polymerase chain reaction and utilized
      to express recombinant glutathione S-transferase (GST) fusion proteins. Double
      immunodiffusion (ID) defined Ro positive autoimmune sera from 12 patients with
      neonatal lupus erythematosus (NLE), 16 with subacute cutaneous lupus
      erythematosus (SCLE) and 12 with primary Sjogren's syndrome (SS) were tested by
      enzyme linked immunosorbent assay (ELISA) against the recombinant 52 and 60 kDa
      Ro fusion proteins. RESULTS: Seventy-five percent of NLE, 56% of SCLE and 83% of
      SS sera reacted with the 52 kDa fusion protein. Seventy-five percent of NLE, 63%
      of SCLE and 83% of SS sera reacted with the 60 kDa fusion protein. Seventeen
      percent of NLE sera, 25% of SCLE sera and 8% of SS sera were nonreactive to both
      full length fusion proteins. Eight (57%) of 14 ID defined Ro negative NLE, SCLE
      and SS sera were reactive with both Ro fusion proteins by ELISA: ELISA studies
      with recombinant 52 and 60 kDa Ro protein fragments revealed at least 2 major
      epitopes on each Ro protein. A fragment of the 52 kDa Ro protein that contains a
      putative leucine zipper motif reacted with 100% of ID defined Ro positive SS
      sera. CONCLUSION: Our data demonstrate that the ID assay and the recombinant Ro
      ELISA together are more sensitive in detecting Ro antibodies than either assay
      alone, and that multiple epitopes are present on both Ro proteins.

PMID- 7523672
TI  - Radiotherapy for bone pain.
AB  - Painful bone metastases are a common problem for cancer patients. Although
      current evidence supports the use of a single fraction of radiotherapy as the
      treatment of choice, many radiotherapists, for a variety of reasons, continue to
      use fractionated regimens. Over one six month period 105 patients received
      external beam irradiation for painful bone metastases at the Royal London
      Hospital (RLH). Thirty-one per cent of the patients were aged 70 or over. The
      treatment of 97 of these patients was assessed. They had a total of 280 sites
      treated over the course of their disease. Fifty-nine per cent of sites treated
      received a fractionated course of radiotherapy. Site significantly influenced
      fractionation. Overall response rates of 82% were achieved. Fractionation did not
      appear to influence this. Ten patients received large field irradiation. Fifteen
      patients had five or more sites irradiated, of whom only one received hemibody
      irradiation.

PMID- 7523674
TI  - Structure--activity relationships of sialyl Lewis x-containing oligosaccharides.
      1. Effect of modifications of the fucose moiety.
AB  - Leukocyte adhesion to the vasculature is mediated by E-, P-, and L-selectins. The
      natural ligands for E- and P-selectins have not been fully characterized but have
      been shown to contain the tetrasaccharide sialyl Lewis x structure (SLe(x)). To
      determine the importance of the fucose moiety of SLe(x), various analogs of
      SLe(x) containing modifications thereof were prepared and tested as inhibitors of
      E-selectin-mediated cell adhesion. Cellular experiments indicate that replacement
      of the hydroxyl groups of fucose by hydrogen abrogated E-selectin binding.
      However, the arabinose analog of fucose (CH3 delta H) inhibited cell adhesion but
      was 5-fold less potent than native SLe(x). This data suggests that modifications
      of fucose on SLe(x) are generally deleterious toward E-selectin binding.

PMID- 7523673
TI  - Synthesis and structure-activity studies on acidic amino acids and related
      diacids as NMDA receptor ligands.
AB  - The 3-isoxazolol amino acids (S)-2-amino-3-(3-hydroxy-5-methyl-4-
      isoxazolyl)propionic acid [(S)-AMPA, 2] and (R,S)-2-amino-2-(3-hydroxy-5-methyl-4
      isoxazolyl)acetic acid (AMAA, 5a) (Figure 1) are potent and specific agonists at
      the AMPA and N-methyl-D-aspartic acid (NMDA) subtypes, respectively, of (S)
      glutamic acid (1) receptors. A number of amino acids and diacids structurally
      related to AMAA were synthesized and tested electrophysiologically and in
      receptor-binding assays. The hydroxymethyl analogue 7c of AMAA was an NMDA
      agonist approximately equipotent with AMAA in the [3H]CPP-binding assay (IC50 = 7
      +/- 3 microM) and electropharmacologically in the rat cortical wedge model (EC50
      = 8 +/- 2 microM). In contrast to this, the tertbutyl analogue 7a of AMAA turned
      out to be an antagonist at NMDA and AMPA receptors. The conformational
      characteristics of AMAA and 7a, c were studied by molecular mechanics
      calculations. Compound 7a possesses extra steric bulk and shows significant
      restriction of conformational flexibility compared to AMAA and 7c, which may be
      determining factors for the observed differences in biological activity. Although
      the nitrogen atom of quinolinic acid (6) has very weak basic character, 6 is a,
      perhaps subtype-selective, NMDA receptor agonist and a potent neurotoxic agent.
      These aspects prompted us to synthesize and test the diacids 8a, b, in which the
      amino group of AMAA has been replaced by a methylthio and methoxy group,
      respectively. Neither compound showed significant affinity for nor depolarizing
      effects at NMDA receptors. The hydroxymethyl AMPA analogue 3c showed no
      interaction with NMDA receptors and only weak AMPA agonist effects.

PMID- 7523676
TI  - Hepatitis C RNA prevalence in a Western European organ donor pool and virus
      transmission by organ transplantation.
AB  - Liver disease is a common finding after organ transplantation and might in part
      be due to transmission of hepatitis C virus (HCV). The aim of this study was to
      determine the prevalence of positive results with different anti-HCV tests and
      HCV-RNA in a local donor pool and to clarify to what extent HCV was transmitted
      to organ recipients. Serum samples from 207 consecutive organ donors were
      analysed retrospectively with anti-HCV ELISA (2nd and 3rd generation), anti-HCV
      RIBA (2nd generation) and HCV polymerase chain reaction (PCR). Organ recipients
      at risk were identified and followed up serologically and clinically. Anti-HCV
      seroprevalance in organ donors was 4.3% for 2nd generation ELISA, 4.8% for 3rd
      generation ELISA and 1.9% for 2nd generation RIBA. HCV-PCR was positive in 1.4%.
      Nine organs from four RIBA-positive donors were transplanted into eight
      recipients of whom four became anti-HCV and PCR positive after transplantation.
      HCV-PCR became positive several days after transplantation whereas anti-HCV
      seroconversion took place after 8-9 months. Two recipients developed acute liver
      disease and another two showed features of mild chronic liver disease but no
      serious complications due to HCV infection were observed.

PMID- 7523675
TI  - Synthesis and evaluation of the anti-HIV activity of aza and deaza analogues of
      isoddA and their phosphates as prodrugs.
AB  - Some aza and deaza analogues of the anti-HIV agent 2',3'-dideoxy-3'-oxoadenosine
      (isoddA) (8-aza-, 8-aza-1-deaza, 8-aza-3-deaza-, 1-deaza-, and 3-deaza-isoddA)
      were synthesized and found inactive against HIV in vitro. The hypothesis that the
      inactivity of these isonucleosides might be due to their poor affinity for
      cellular nucleoside kinases was checked by the synthesis of a series of 5'
      [bis(2,2,2-trichloroethyl) phosphate] triesters and 5'-phenyl phosphoramidate
      derivatives which, acting as membrane soluble prodrugs, could release the free
      phosphate form inside the cell. The 5'-(phenylmethoxy)alaninyl phosphate derived
      from 8-aza-isoddA was found active against HIV-1 and HIV-2 with a potency similar
      to that of isoddA, while the anti-HIV potency of 5'-(phenylmethoxy)alaninyl
      phosphate of isoddA proved remarkably higher than that of isoddA, in particular
      against HIV-2, being similar to that of AZT. Further evidence that 8-aza-isoddA
      could behave as anti-HIV agent, provided that it is activated as phosphate, was
      obtained by the synthesis of its 5'-triphosphate derivative, which proved to be
      an active inhibitor of HIV-1 recombinant reverse transcriptase.

PMID- 7523678
TI  - A comparative study of ribotyping and arbitrarily primed polymerase chain
      reaction for investigation of hospital outbreaks of Acinetobacter baumannii
      infection.
AB  - Arbitrarily primed polymerase chain reaction (AP-PCR) and ribotyping were
      compared in an investigation of an outbreak of Acinetobacter baumannii
      infections. Twenty-five clinical isolates shown previously by other criteria to
      belong to two different groups, and nine randomly selected A. baumannii clinical
      isolates from other hospitals were investigated. Among the strains analysed, nine
      different EcoRI rRNA gene restriction pattern fingerprints were observed. While
      similarity was detected between strains of the same group, these fingerprints
      differed clearly between the two A. baumannii groups defined in the outbreak. Two
      of the nine strains selected randomly had the same ribotype as those strains
      involved in the outbreak, whereas the remaining seven strains each had a
      different ribotype. When the strains were tested by AP-PCR with 0.25, 0.5 or 1
      microM of M13 forward primer, 10 different profiles were obtained. However, 11
      profiles were observed if two different primer concentrations (0.25 and 1 microM)
      were used. It was concluded that ribotyping and AP-PCR exhibited a similar
      discriminatory power, although AP-PCR had the additional advantages of speed and
      simplicity.

PMID- 7523677
TI  - Lipo-oligosaccharide immunotyping of Neisseria meningitidis by a whole-cell ELISA
      with monoclonal antibodies.
AB  - To assess the applicability of a whole-cell ELISA (WCE) with monoclonal
      antibodies (MAbs) for lipo-oligosaccharide (LOS) immunotyping of Neisseria
      meningitidis, 675 meningococcal isolates obtained in 1989 and 1990 in the
      Netherlands and 57 isolates collected in 1974, of which the immunotype had been
      determined previously by microprecipitation, were analysed. Despite the lack of
      specific MAbs for L2 and L4, an algorithm was developed for the assignment of
      immunotypes on the basis of the reaction patterns of the reference strains and
      these isolates to a combination of 14 MAbs. The immunotypes found by WCE were in
      accordance with those obtained by microprecipitation and the results from WCE
      were reproducible. The distribution of immunotypes among isolates of the various
      serogroups in the Netherlands in 1989-1990 is presented. Based on the reaction
      patterns of the isolates, two main categories of related immunotypes could be
      distinguished among isolates of serogroups B and C: L2/L4 and L3/L1/L8. Some
      isolates of the latter category were of one immunotype, but many isolates
      expressed one or two additional immunotypes, either strongly or weakly,
      indicating that the differences in this category are quantitative rather than
      qualitative. The results of this study have demonstrated that the WCE method for
      LOS immunotyping is easily applicable and provides better definition of test
      strains for in-vitro bactericidal assays and research into pathogenesis.

PMID- 7523679
TI  - Crystals of HIV-1 reverse transcriptase diffracting to 2.2 A resolution.
AB  - Reverse transcriptase (RT) from the human immunodeficiency virus type 1 has been
      crystallized in four closely related forms, the best of which diffract X-rays to
      2.2 A resolution. The RT was crystallized as a complex with a non-nucleoside
      inhibitor, either nevirapine or a nevirapine analogue. Crystals grew from 6% PEG
      3400 buffered at pH 5. These were of space group P2(1)2(1)2(1) with unit cell
      parameters a = 147 A, b = 112 A, c = 79 A (form A), with one RT heterodimer in
      the asymmetric unit. Changes in unit cell parameters and degree of crystalline
      order were observed on soaking pregrown crystals in various solutions, giving
      three further sets of unit cells. These were a = 143 A, b = 112, A, c = 79 A
      (form B), a = 141 A, b = 111 A, c = 73 A (form C), a = 143 A, b = 117 A, c = 66.5
      A (form D). The last two forms diffract X-rays to 2.2 A resolution. Structure
      determinations of these latter crystal forms of RT should give a detailed atomic
      model for this therapeutically important drug target.

PMID- 7523680
TI  - Crystallization and preliminary X-ray diffraction studies of human RANTES.
AB  - The chemotactic cytokine RANTES (Regulated on Activation, Normal T-cell Expressed
      and Secreted) is a potent chemoattractant and activator of a number of
      leukocytes, with a molecular mass of 8 kDa. Crystals of this protein have been
      grown from 100 mM sodium acetate buffer (pH 4.6) containing 200 mM magnesium
      acetate, with 20% (w/v) PEG 4000 and 6% (v/v) glycerol. The crystals grow as
      thick rods, which diffract to at least 1.8 A resolution on a rotating anode X-ray
      source. The crystals belong to space group p2(1)2(1)2(1) with unit cell
      dimensions a = 95.14 A, b = 57.58 A and c = 24.01 A with alpha = beta = gamma =
      90 degrees. The asymmetric unit contains two molecules of the RANTES monomer,
      with a VM of 2.0 A(3)/Da.

PMID- 7523682
TI  - Structural mimicry and enhanced immunogenicity of peptide epitopes displayed on
      filamentous bacteriophage. The V3 loop of HIV-1 gp120.
AB  - The principal neutralizing determinant of the human immunodeficiency virus type 1
      (HIV-1) is an intra-chain disulphide-bridged loop, designated V3, in the third
      hypervariable region of the surface glycoprotein gp120. Peptide sequences from
      the V3 loop of gp120 from HIV-1 strain MN (HIV-1MN) were engineered into the N
      terminal region of the major coat protein of filamentous bacteriophage fd,
      leading to their display in multiple copies on the surface of the bacteriophage
      virion. Peptides displayed in this way were shown to be remarkably effective
      structural mimics of the natural epitope. They were recognised by human HIV
      antisera and evoked high titres of antibodies in mice, which cross-reacted with
      other strains of HIV and were capable of neutralizing the virus. In addition,
      antibody production could be stimulated by simultaneous inoculation with T-cell
      epitopes similarly displayed on filamentous bacteriophage. The bacteriophage
      display system offers a powerful means of studying the immunological recognition
      of proteins and is a promising vaccine model.

PMID- 7523681
TI  - Isolated P2 rRNA promoters of Escherichia coli are strong promoters that are
      subject to stringent control.
AB  - Ribosomal RNA synthesis in Escherichia coli is under stringent control. The seven
      rRNA operons are highly conserved and are each transcribed from two tandem
      promoters, P1 and P2, which are located about 120 base-pairs apart. In
      exponentially growing cells the majority of the transcripts are initiated at the
      P1 promoters. The P1 promoters are highly regulated, and are under stringent as
      well as growth rate controls. Here we demonstrate that transcription from the
      rrnA P1 promoter diminishes P2 expression. In the absence of P1, the P2 promoter
      acts as a rather strong promoter. Insertion of a transcription terminator between
      P1 and P2 eliminates the inhibition of P2 by P1, suggesting that the physical
      movement of RNA polymerase originating at P1 and progressing along the P2
      promoter is necessary for the interference process to take place. Similarly to
      P1, the solitary P2 promoter is subject to stringent control.

PMID- 7523683
TI  - Single base-pair deletions induced by bleomycin at potential double-strand
      cleavage sites in the aprt gene of stationary phase Chinese hamster ovary D422
      cells.
AB  - One possible mechanism for the generation of deletion mutations is inaccurate
      repair of DNA double-strand breaks. In an attempt to detect such aberrant repair
      events in intact cells, confluent stationary phase cultures of chinese hamster
      ovary D422 cells, which are hemizygous for aprt, were treated for two days with
      low concentrations of bleomycin, and aprt mutant clones were selected and
      analyzed by polymerase chain reaction and DNA sequencing. Bleomycin was quite
      mutagenic in stationary phase cells, increasing the mutant frequency by five to
      40-fold at 5 to 50% survival. While spontaneous mutations generated under these
      conditions were predominantly base substitutions, the majority of the bleomycin
      induced mutations were very small deletions, with lesser numbers of large
      deletions/rearrangements and base substitutions. Although the small deletions
      tended to be clustered in several short segments of the gene, nucleosome
      positioning studies indicated that there was no consistent phasing of nucleosomes
      in aprt, suggesting that the clustering was due to sequence specificity rather
      than chromatin structure. About half of the bleomycin-induced mutations were
      single-base-pair (-1) deletions, and the majority of these involved deletion of
      one C in a G-Cn sequence (n > or = 2). At such sites, bleomycin is known to
      induce double-strand breaks by fragmentation of deoxyribose moieties at the same
      sequence position in both strands, resulting in a blunt-ended double-strand break
      with 5'-phosphate and 3'-phosphoglycolate termini. Thus, this sequence
      specificity is consistent with a model in which bleomycin-induced -1 deletions
      are generated by a double-strand break rejoining process involving removal of
      phosphoglycolate moieties from both 3' ends, followed by blunt-end ligation. The
      results support the view that repair of free radical-mediated double-strand
      breaks in mammalian cells in G1/G0 phase can be effected by such simple end
      joining mechanisms, without the need for homologous recombination.

PMID- 7523684
TI  - Preparation, characterization and crystallization of an antibody Fab fragment
      that recognizes RNA. Crystal structures of native Fab and three Fab
      mononucleotide complexes.
AB  - Fab fragments from Jel 103, an antibody which specifically binds to single
      stranded poly(rl), were prepared by papain digestion, separated into eight
      isoforms and characterized by mass spectrometry. One of the purified isoforms
      yielded crystals suitable for structural studies by X-ray diffraction and its
      crystal structure was determined to 2.4 A resolution. Soaking the crystals in
      solutions containing either of the mononucleotides inosine-5'-diphosphate,
      guanosine-5'-diphosphate or deoxyinosine-5'-monophosphate resulted in binding of
      the nucleotide in a single binding site. However, adenosine-5'-diphosphate does
      not bind to this antibody. The recognition of the base is achieved through
      hydrogen bonds to the C6 carbonyl oxygen and the imino NH group of the purine in
      a pattern similar to that of the base-base interactions in a double-stranded
      nucleic acid. Additional binding energy is provided by stacking of the base and
      the Tyr32L side-chain and by interaction of the alpha-phosphate with the antibody
      in an anionic binding site. Most of the side-chains interacting with the
      nucleotide come from the light chain. Surprisingly, this antibody shares the VL
      sequence with another nucleic acid-binding antibody, BV04-1. The latter binds to
      a single stranded DNA with a high preference for thymine bases. The structures of
      the unliganded and complexed Jel 103 Fab are compared to those of BV-04-1 Fab and
      while they show similarity in recognition of the base of the immunodominant
      nucleotide, their 5' phosphates occupy different positions, suggesting different
      orientation of the nucleic acid bound to these two antibodies. Differences in the
      conformations of the L1 loops between the two Fabs have been noted.

PMID- 7523685
TI  - Ultrastructural studies of diffuse axonal injury in humans.
AB  - Diffuse axonal injury (DAI) is observed commonly in traumatically brain injured
      humans. However, traditional histologic methods have proven of limited use in
      identifying reactive axonal change early (< 12 h) in the posttraumatic course.
      Recently, we have reported, in both humans and animals, that antibodies targeting
      neurofilament subunits are useful in the light microscopic recognition of early
      reactive change. In the present study, we extend our previous efforts in humans
      by analyzing the progression of traumatic brain injury (TBI)-induced axonal
      change at the ultrastructural level. This effort was initiated to follow the
      subcellular progression of reactive axonal change in humans and to determine
      whether this progression parallels that described in animals. Two commercially
      prepared antibodies were used to recognize reactive axonal change in patients
      surviving from 6 to 88 h. The NR4 antibody was used to target the light
      neurofilament subunit (NF-L), and the SMI32 antibody was used to target the heavy
      neurofilament subunit (NF-H). Plastic-embedded tissue sections were screened for
      evidence of reactive axonal change, and once identified, this reactive change was
      analyzed at the ultrastructural level. At 6 h survival, focally enlarged,
      immunoreactive axons with axolemmal infolding or disordered neurofilaments were
      seen within fields of axons exhibiting no apparent abnormality. By 12 h, some
      axons exhibited continued neurofilamentous misalignment, pronounced
      immunoreactivity, vacuolization, and, occasionally, disconnection. At later
      stages, specifically 30 and 60 h survival, further accumulation of neurofilaments
      and organelles had led to the further expansion of the axis cylinder, and clearly
      disconnected reactive swellings were recognized. These contained a dense core of
      disordered immunoreactive neurofilaments partially encompassed by a cap of less
      densely aggregated organelles. At 88 h, the reactive axons were larger and
      elongated, consistent with the continued delivery of organelles by axoplasmic
      transport. At the later time points, considerable heterogeneity was observed,
      with focally enlarged disconnected axons being observed in relation to axons
      showing less advanced reactive change. Our findings suggest that neurofilamentous
      disruption is a pivotal event in axonal injury.

PMID- 7523686
TI  - 5'-flanking sequences of the human HPRT gene direct neuronal expression in the
      brain of transgenic mice.
AB  - Total deficiency of hypoxanthine phosphoribosyltransferase (HPRT) in humans
      causes the neurological disorder Lesch-Nyhan syndrome. The HPRT gene is expressed
      at basal levels in all tissues but at higher levels in the brain, the relevance
      and mechanism of which is unknown. To determine if cis-acting DNA elements play a
      role in the tissue-differential pattern of expression, we generated transgenic
      mice carrying different sequences of the human HPRT (hHPRT) promoter fused to the
      bacterial lacZ gene. We show that a 1.6 kb fragment of the hHPRT promoter
      contains essential information to direct beta-galactosidase expression
      preferentially to the basal ganglia, cerebral cortex, hippocampus, and several
      other areas of the forebrain. At least two elements within the 1.6 kb fragment
      appear to be required for neuronal expression. A 182 bp element (hHPRT-NE)
      represents one of these sequences and is involved not only in conferring neuronal
      specificity but also in repressing transgene expression in non-neuronal tissues.
      These studies provide molecular insight into the mechanism of increased HPRT
      expression in the brain.

PMID- 7523687
TI  - Differentiation of oligodendrocytes cultured from developing rat brain is
      enhanced by exogenous GM3 ganglioside.
AB  - Cultures consisting primarily of O-2A progenitor cells and immature
      oligodendrocytes with a few microglia and astrocytes were obtained by shaking
      primary cultures from neonatal rat brain after 12-14 days in vitro. Addition of
      50 micrograms/ml exogenous Neu-NAc alpha 2-3Gal beta 1-4Glc beta 1-1'ceramide
      (GM3 ganglioside) to the cultures resulted in an increase in the number and
      thickness of cell processes that stained intensely for sulfatide and
      galactocerebroside (galC) in comparison to control cultures without added GM3.
      The treated cultures also contained fewer astrocytes than control cultures as
      revealed by immunostaining for glial fibrillary acidic protein (GFAP). Cells that
      immunostained for both GFAP and sulfatide/galC were very rare in control cultures
      but were frequently seen in the GM3-treated cultures, suggesting that these may
      represent cells changing their direction of differentiation away from type II
      astrocytes toward oligodendrocytes under the influence of GM3. These effects on
      the developing rat oligodendrocytes were specific for GM3 ganglioside and were
      not produced by adding GM1, GM2, GD3, or GD1a to the cultures. Lactosyl ceramide
      and neuraminyl lactose were also ineffective. When control cultures were
      initially plated on polylysine and incubated with [14C]galactose, GD3 was the
      principal labeled ganglioside. However, as the control cells differentiated over
      time in culture without the addition of exogenous GM3 and produced increasing
      amounts of myelin-related components, the incorporation of [14C]galactose into
      endogenous GM3 increased to become the predominant labeled ganglioside by 6 days
      after plating. Metabolic labeling of the GM3-treated oligodendrocytes with
      [14C]galactose revealed increased incorporation into galC and sulfatide in
      comparison to control cultures, but a decreased labeling of endogenous GM3.
      Similarly, incorporation of an amino acid precursor into the myelin-associated
      glycoprotein (MAG) was increased by GM3 treatment, but incorporation into myelin
      basic protein (MBP) was not affected. Although the overall effect of added GM3
      was to decrease the phosphorylation of most proteins in the oligodendrocytes,
      including MBP, GM3 enhanced the phosphorylation of MAG. These findings indicate
      that GM3 ganglioside has an important role in the differentiation of cells of the
      O-2A lineage toward myelin production, since differentiation is associated with
      increased metabolic labeling of endogenous GM3 in control cultures and is
      enhanced by the addition of exogenous GM3.

PMID- 7523688
TI  - Astrocyte-derived lipoxygenase product evokes endothelium-dependent relaxation of
      the basilar artery.
AB  - The goal of this study was to examine the possible production of vasoactive
      factors by astrocytes. We consistently observe that rat astroglial cells in
      suspension produce marked relaxation when added to precontracted rings of intact
      (but not endothelium-denuded) rabbit basilar artery. The ultimate mediator of
      this relaxation was endothelium-derived nitric oxide whose synthesis is activated
      by an as yet unidentified factor(s) produced tonically by astrocytes. The factor
      is relatively stable, and is not arachidonate, or a product of cyclooxygenase or
      P450 metabolism. Based upon studies with selective inhibitors, the factor appears
      to result from 12- or 15-lipoxygenase metabolism, the products of which are known
      to be vasoactive. In a separate series of experiments, astrocyte-conditioned
      medium stimulated the production of citrulline from L-arginine by nitric oxide
      synthase in bovine aortic endothelial cells. The possible significance for
      central nervous system (CNS) pathophysiology of an astrocyte-derived vasodilator
      is discussed.

PMID- 7523689
TI  - Reactive astrocytes are widespread in the cortical gray matter of amyotrophic
      lateral sclerosis.
AB  - The distribution of reactive astrocytes was examined in the cortical gray matter
      of non-motor and motor regions from cases of familial and sporadic amyotrophic
      lateral sclerosis (ALS) and compared to that of beta-amyloid deposits. By glial
      fibrillary acidic protein immunocytochemistry, patches of reactive astrocytes,
      characterized by multiple reactive astrocytes in a circular or patch-like
      formation, occurred in 12 of 15 ALS cases examined. These patches of reactive
      astrocytes were not restricted to the motor cortex but were found in the gray
      matter in ALS in all examined brain regions, including frontal, temporal,
      inferior parietal, cingulate, occipital, and motor cortices, from both familial
      and sporadic ALS cases. Reactive astrocytes were also found in the subpial region
      and at the gray/white matter junction. Because patches of astrocytes can occur in
      association with senile plaques, beta-amyloid was localized. By immunostaining,
      beta-amyloid deposits were observed in five of the 15 ALS cases: three cases had
      only early plaques, two had both early and classic plaques. The number of ALS
      cases with both astrocyte patches and amyloid plaques was four of 15, but
      typically astrocyte patches in ALS occurred without any evidence of an
      association with beta-amyloid deposits. Therefore, the astrocyte patches in ALS
      are not the result of beta-amyloid deposition. The widespread occurrence of
      reactive astrocytes, as patches in the cortical gray matter and in the subpial
      region and at the gray/white matter junction, is evidence of a widespread
      pathology in ALS cortex in both familial and sporadic forms of the disease.

PMID- 7523690
TI  - Astrogliosis in culture: III. Effect of recombinant retrovirus expressing
      antisense glial fibrillary acidic protein RNA.
AB  - Injury to the central nervous system (CNS) either from trauma or due to
      demyelinating/degenerating diseases results in a typical response of astrocytes,
      termed astrogliosis. This reaction is characterized by astrocyte proliferation,
      extensive hypertrophy of nuclei, cell body, and cytoplasmic processes and an
      increase in immunodetectable glial fibrillary acidic protein (GFAP). GFAP
      accumulation may cause a physical barrier preventing the reestablishment of a
      functional environment. Our studies have aimed at modulating astrogliosis by
      inhibiting or delaying GFAP synthesis in damaged and reactive astrocytes. The
      present study investigates the use of a recombinant retrovirus expressing
      antisense GFAP RNA in controlling the response of mechanically injured
      astrocytes. A 650 bp fragment from the coding region of mouse GFAP cDNA was
      cloned in the antisense orientation under the control of long terminal repeat
      (LTR) promoter of Moloney murine leukemia virus. Increase in GFAP as detected by
      immunocytochemical staining in injured astrocytes was inhibited by treatment with
      retrovirus expressing antisense GFAP RNA. Also, astrocytes at the site of injury
      in these scratched cultures did not show cell body hypertrophy compared to
      control cultures. These observations demonstrate that the increase in GFAP at the
      site of injury can be inhibited using retroviral treatment and indicate the
      potential of retrovirus-mediated gene transfer in modulating scar formation in
      the CNS in vivo. These studies also shed light on the role of GFAP in maintaining
      the morphology of astrocytes.

PMID- 7523691
TI  - Monoamine-activated alpha 2-macroglobulin inhibits choline acetyltransferase of
      embryonic basal forebrain neurons and reversal of the inhibition by NGF and BDNF
      but not NT-3.
AB  - Monoamine-activated alpha 2-macroglobulin (alpha 2M) has recently been shown to
      inhibit the growth and survival of cholinergic neurons of the basal forebrain
      (Liebl and Koo: J Neurosci Res 35:170-182, 1993). The mechanism of this
      inhibitory effect is believed to involve the regulation of growth factor
      activities by alpha 2M. The objectives of this study are to determine whether
      monoamine-activated alpha 2M can inhibit choline acetyltransferase (ChAT)
      activity of cholinergic basal forebrain neurons, and whether some common
      neurotrophins in the CNS can reverse the inhibition. This study demonstrates that
      both methylamine-activated alpha 2M (MA-alpha 2M) and serotonin-activated alpha
      2M (5HT-alpha 2M) can dose-dependently suppress the expression of normal basal
      levels of ChAT activity in embryonic rat basal forebrain cells in vitro, while
      normal alpha 2M has little or no effect. As little as 0.35 microM monoamine
      activated alpha 2M can suppress the ChAT activity, whereas either nerve growth
      factor (NGF) or brain-derived neurotrophic factor (BDNF), but not neurotrophin-3
      (NT-3), stimulates ChAT expression of these cells. The addition of either NGF or
      BDNF to the alpha 2M-suppressed cells can increase ChAT activity back to its
      normal levels, while NT-3 can not. These results demonstrate that (1) monoamine
      activated alpha 2M is a potent non-cytotoxic inhibitor of the ChAT activity in
      cholinergic basal forebrain neurons, and (2) NGF and BDNF are capable of not only
      stimulating the ChAT activity but can also specifically reverse the alpha 2M
      inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523692
TI  - Retrograde axonal transport of locally synthesized proteins, e.g., actin and heat
      shock protein 70, in regenerating adult frog sciatic sensory axons.
AB  - The local synthesis and subsequent retrograde axonal transport of [35S]methionine
      labelled proteins was studied in the in vitro regenerating adult frog sciatic
      sensory axons. By the use of a three compartment culture system, proteins in the
      outgrowth region were selectively labelled. After 2 days in culture a rise in TCA
      insoluble radioactivity was detected in the dorsal root ganglia, which could be
      prevented by the addition of vinblastine or 2,4-dinitrophenol to the nerve
      proximal to the crush site. Two-dimensional polyacrylamide gel electrophoresis of
      ganglionic proteins revealed a pattern of 35 labelled polypeptides with apparent
      molecular masses (Mm) ranging from < 15 to 95 kDa and with isoelectric points
      (pI) ranging from 4.5 to 6.5. The major ones, representing about 75% of the
      activity in a gel, were of Mm/pI 47/5.4, 48/6.1,. 57/6.0, 62/5.2, 65/4.9-5.0,
      65/5.2, and 81/5.4 respectively. One of these polypeptides (47/5.4) was
      identified as actin and another (81/5.4) as a member of the heat shock protein 70
      family. The spots at 65/4.9-5.0 were tubulin isoforms. There was a striking
      similarity between transported proteins on one hand, and proteins synthesized in
      the injured nerve on the other, with respect to the Mm/pI of at least 14 protein
      species. The results suggest that a selected set of proteins, synthesized by non
      neuronal cells, e.g., Schwann cells, is transferred to the ganglionic cell bodies
      by retrograde axonal transport.

PMID- 7523693
TI  - Serotonin inhibits outgrowth of goldfish retina and impairs the trophic effect of
      taurine.
AB  - The regeneration of explants prepared from goldfish retinas with a prior crush of
      the optic nerve is stimulated by the sulphur amino acid, taurine. Serotonin has
      been reported to modify survival, proliferation, and outgrowth of nervous tissue.
      In the present work we evaluated the effect of serotonin and some serotonergic
      agonists on the neuritic outgrowth from goldfish retinal explants. Serotonin, its
      precursor, 5-hydroxytryptophan, and the 5HT1A receptor agonists, 8-hydroxy-2-(di
      n-propylamino)tetralin and buspirone, inhibited the outgrowth. The blockers of
      serotonin uptake, imipramine and citalopram, were also inhibitors of neurite
      sprouting. Imipramine favoured the inhibitory effect of serotonin at 10 days in
      culture. The concentration of serotonin and its metabolite, 5-hydroxyindoleacetic
      acid, decreased in the retina at 3 and 5 days after the crush of the optic nerve.
      Serotonin levels started to recover after 5 days post-lesion, and the metabolite
      also increased. This indicates that the lesion increases the turnover rate of
      serotonin and this may be related to its role in regeneration. Serotonin
      concentration was elevated by the intraocular administration of its precursor, 5
      hydroxytryptophan, indicating that the capacity for synthesis was preserved after
      the crush, but that it was smaller in the post-lesioned retinas. The trophic
      effect of taurine was impaired by a low concentration of serotonin, probably by
      opposing the final effect on growth via different targets. These results support
      a role of serotonin in the regeneration of goldfish retina probably through 5HT1A
      receptors.

PMID- 7523694
TI  - Cerebral artery Doppler ultrasonography for prediction of outcome after perinatal
      asphyxia.
AB  - Perinatal asphyxia is the most common cause of neurologic injury and
      neurodevelopmental delay. The signs of injury are nonspecific at birth, and most
      indicators take hours to days before they become manifest. Early recognition of
      the injury is important in guiding management during those critical first days of
      life. Over a five-year period, we investigated 16 term neonates with a history of
      asphyxia on the first day of life who demonstrated on intracranial Doppler
      sonography cerebral vessel high diastolic flow with a resistive index below 60.
      Two infants died and one was lost to follow-up. Three of the remaining 13
      patients were normal at 8 months to 1 year follow-up. The remaining 10 patients
      had severe neurodevelopmental delay with profound handicaps at follow-up periods
      from 3 months to 32 months. This study has confirmed earlier reports that in the
      first days of life, a very low resistive index combined with history of asphyxia
      is associated with an adverse outcome and may be considered one of the earliest
      markers for poor neurodevelopmental outcome. Only 50% of these patients
      demonstrated abnormal sonographic imaging.

PMID- 7523696
TI  - Artificial mosaic protein containing antigenic epitopes of hepatitis E virus.
AB  - A synthetic gene encoding an artificial polypeptide composed of antigenic
      epitopes of the hepatitis E virus (HEV) proteins was constructed from short
      oligodeoxyribonucleotides by using PCR. The polypeptide comprises a mosaic of
      three antigenically active dominant regions from the protein encoded by open
      reading frame 2 (ORF2), one antigenically active region from the protein encoded
      by ORF3 of the Burmese HEV strain, and one antigenically active region from the
      protein encoded by ORF3 of the Mexican HEV strain. The mosaic protein was
      expressed in Escherichia coli as a chimera with glutathione S-transferase or beta
      galactosidase. Guinea pig sera containing antibodies to the corresponding HEV
      synthetic peptides were used to demonstrate by Western immunoblot analysis and
      enzyme immunoassay the presence and accessibility of all HEV-specific antigenic
      epitopes introduced into the mosaic protein. Both the glutathione S-transferase
      and beta-galactosidase hybrid proteins were analyzed by using a panel of human
      anti-HEV-positive and -negative sera. The data obtained strongly indicate a
      diagnostic potential for the mosaic protein.

PMID- 7523695
TI  - Analysis of the primary T-cell response to Sendai virus infection in C57BL/6
      mice: CD4+ T-cell recognition is directed predominantly to the hemagglutinin
      neuraminidase glycoprotein.
AB  - Sendai virus infection of C57BL/6 mice elicits a strong CD4+ and CD8+ T-cell
      response in the respiratory tract. To investigate the specificity of the CD4+ T
      cell response, a panel of hybridomas was generated from cells recovered from the
      respiratory tracts of infected mice. Using vaccinia virus recombinants expressing
      individual Sendai virus proteins, we found that the majority of these hybridomas
      (34 of 37) were specific for the hemagglutinin-neuraminidase (HN) glycoprotein.
      The hybridomas were then analyzed for reactivity to a set of overlapping peptides
      spanning the entire length of the hemagglutinin-neuraminidase glycoprotein. At
      least five H-2 I-Ab-restricted epitopes were defined in HN. The strong bias
      toward recognition of class II epitopes derived from a single viral protein
      contrasts with T-cell recognition of epitopes of several proteins in influenza A
      virus as found previously by others.

PMID- 7523697
TI  - Vaccines prepared from chimeras of foot-and-mouth disease virus (FMDV) induce
      neutralizing antibodies and protective immunity to multiple serotypes of FMDV.
AB  - The G-H loop of VP1 (residues 132 to 159) of foot-and-mouth disease virus (FMDV)
      is a prominent feature on the virion surface and has an important role in vaccine
      efficacy, generation of antigenic variants, and cell binding. Using an infectious
      cDNA of FMDV, we have constructed serotype A viruses in which the G-H loop has
      been substituted with the homologous sequences from serotype O or C. These
      chimeric viruses replicated to high titer and displayed plaque morphologies
      similar to those of wild-type viruses, demonstrating that the functions provided
      by the loop can be readily exchanged between serotypes. Monoclonal antibody
      analyses showed that epitopes contained within the loop were transferred to the
      chimeras and that epitopes encoded by the type A backbone were maintained.
      Chemically inactivated vaccines prepared from chimeric viruses induced antibodies
      in guinea pigs that neutralized both type A and either type O or type C viruses.
      Swine inoculated with the A/C chimera vaccine also produced cross-reactive
      antibodies, were protected from challenge with the type A virus, and partially
      protected against challenge with type C. These studies emphasize the importance
      of epitopes outside of the G-H loop in protective immunity in swine, which is a
      natural host of FMDV.

PMID- 7523698
TI  - Scanning mutagenesis of the arginine-rich region of the human immunodeficiency
      virus type 1 Rev trans activator.
AB  - The structural proteins of human immunodeficiency virus type 1, for example, Gag
      and Env, are encoded by unspliced and incompletely spliced viral transcripts. The
      expression of these mRNAs in the cytoplasm, along with their commensurate
      translation, is absolutely dependent on the virally encoded Rev trans activator.
      Previous studies have demonstrated that Rev binds directly to its substrate mRNAs
      via an arginine-rich element that also serves as its nuclear localization
      sequence. In an attempt to define the specific amino acid residues that are
      important for in vivo activity, we have constructed a series of missense
      mutations that scan across this region. Our data demonstrate that all eight
      arginine residues within this element can, individually, be substituted for
      either leucine or lysine with no apparent loss of function. Importantly, these
      findings suggest that no single amino acid within the arginine-rich domain of Rev
      is, by itself, essential for activity and that considerable functional redundancy
      is therefore likely to exist within this region. Interestingly, one mutant in
      which a tryptophan had been substituted for a serine failed to accumulate
      exclusively in the nucleus but still bound RNA in a manner that was
      indistinguishable from that of the wild-type protein. This observation indicates
      that features of the arginine-rich region that are additional to those required
      for RNA binding are important for Rev's correct accumulation in the nucleus.

PMID- 7523699
TI  - Identification of multirestricted immunodominant regions recognized by cytolytic
      T lymphocytes in the human immunodeficiency virus type 1 Nef protein.
AB  - Peripheral blood mononuclear cells from a large number of human immunodeficiency
      virus (HIV)-seropositive donors were used to analyze the CD8+ T-cell response to
      each part of the Nef protein of HIV-1/LAI. This report identifies an
      immunodominant region (amino acids 73 to 144) in the Nef protein that was
      recognized by 97% of the NEF responder donors. This peptide sequence was
      dissected into four epitopic regions (amino acids 73 to 82, 83 to 97, 113 to 128,
      and 126 to 144), each of which was recognized under different HLA class I
      restrictions. Short overlapping peptides were used to sensitive the target cells
      for cytolysis and so to determine if these epitopic regions were multirestricted.
      Each region was found to contain several epitopes recognized with different HLA
      molecules. Thus, the central region of the Nef protein, a regulatory protein
      expressed early in HIV-infected cells, is rich in epitopic sequences which are
      found to be similar in many infected individuals and which can be recognized in
      association with at least ten HLA class I molecules. Their implications for the
      vaccination of humans with peptide sequences are discussed.

PMID- 7523700
TI  - Neutralization of bovine papillomavirus by antibodies to L1 and L2 capsid
      proteins.
AB  - We have generated four mouse monoclonal antibodies (MAbs) to bovine
      papillomavirus virions that bound type-specific, adjacent, and conformationally
      dependent epitopes on the L1 major capsid protein. All four MAbs were
      neutralizing at ratios of 1 MAb molecule per 5 to 25 L1 molecules, but only three
      effectively blocked binding of the virus to the cell surface. Therefore,
      antibodies can prevent papillomavirus infection by at least two mechanisms:
      inhibition of cell surface receptor binding and a subsequent step in the
      infectious pathway. The neutralizing epitopes of the bovine papillomavirus L2
      minor capsid protein were mapped to the N-terminal half of L2 by blocking the
      neutralizing activity of full-length L2 antiserum with bacterially expressed
      peptides of L2. In addition, rabbit antiserum raised against amino acids 45 to
      173 of L2 had a neutralizing titer of 1,000, confirming that at least part of the
      N terminus of L2 is exposed on the virion surface.

PMID- 7523701
TI  - Poor transduction efficiency of human hematopoietic progenitor cells by a high
      titer amphotropic retrovirus producer cell clone.
AB  - The transduction efficiency of human bone marrow CD34+ cells with supernatants
      from the retrovirus producer cell clone PA317/LGSN 16 was only one-fifth of that
      with supernatants from GP+ envAm12/LGSN 15, even though both producers had
      similar infection titers on 3T3 cells. PA317/LGSN 16-conditioned medium inhibited
      the proliferation of the bone marrow CD34+ cells, and this inhibitory effect was
      partially blocked by anti-transforming growth factor beta antibodies. These
      studies suggest that cytokine secretion plays a role in the suppression of
      retrovirus transduction of human CD34+ cells.

PMID- 7523702
TI  - The clinical usefulness of prostate specific antigen: update 1994.
AB  - In conclusion, PSA is the first prostate specific serum marker of clinical
      usefulness in urology. It represents a valuable clinical tool that has improved
      our ability to detect early prostate cancer and to monitor response to therapy.
      While large PSA screening studies have demonstrated an appreciable increase in
      the detection of organ confined, potentially curable prostate cancers, no study
      to date has yet demonstrated that the increased detection rate will decrease the
      prostate cancer-specific mortality rate. Yet more importantly, no study to date
      has demonstrated that early diagnosis using PSA will not decrease the prostate
      cancer specific mortality rate and until such data exist, PSA should be used to
      aid in early diagnosis and treatment planning for men with prostate cancer. PSA,
      when combined with other variables such as Gleason score and clinical stage,
      improves the prediction of pathological stage for prostate cancer. The
      introduction of PSA velocity and age specific reference ranges should further
      enhance the clinical usefulness of PSA. New advances in PSA research hold great
      promise for further improvements in PSA, and truly make it the most important and
      useful tumor marker for adenocarcinoma of the prostate.

PMID- 7523703
TI  - Treatment of post-prostatectomy stress urinary incontinence with periurethral
      polytetrafluoroethylene paste injection.
AB  - Periurethral injection of polytetrafluoroethylene (Teflon) paste was performed to
      treat moderate to severe stress urinary incontinence following prostatectomy. A
      total of 20 procedures was performed in 13 men, of whom 8 had previously
      undergone radical prostatectomy for prostate cancer and 5 had undergone
      transurethral electrocautery resection of the prostate for bladder outlet
      obstruction due to benign prostatic hyperplasia. All patients had significant
      stress urinary incontinence requiring a minimum of 2 pads wet daily. Between 16
      and 20 cc polytetrafluoroethylene paste were injected initially transurethrally
      into the periurethral tissues in the region of the external sphincter. Of the 13
      patients 7 underwent a second injection procedure with an additional 12 to 23 cc
      paste. Three men (23%) experienced a noticeable improvement in continence status,
      including 1 of 5 patients after transurethral electrocautery resection and 2 of 8
      after radical prostatectomy. However, none of these men became completely dry or
      was able to eliminate completely the use of pads. Of the 13 patients 10 (77%)
      experienced no detectable improvement in continence status. Seven patients have
      now successfully undergone implantation of an artificial urinary sphincter
      without complication. With a minimum followup of 11 months in all patients and a
      maximum followup of 3 years, none has experienced any clinically detectable long
      term side effects related to the polytetrafluoroethylene injection or evidence of
      particulate migration.

PMID- 7523704
TI  - Radioimmunoscintigraphy with 111indium labeled CYT-356 for the detection of
      occult prostate cancer recurrence.
AB  - We assessed the safety and ability of the 111indium labeled immunoconjugate 7E11
      C5.3-glycyl-tyrosyl-(N,e-diethylenetriaminepentaacetic acid)-lysine (CYT-356) to
      detect sites of occult prostate cancer in 27 subjects who had undergone radical
      prostatectomy and whose only evidence of recurrent disease was an increasing (0.8
      ng./ml. or greater) serum prostate specific antigen (PSA). All subjects underwent
      whole body scintigraphy between 2 and 4 days following the radiopharmaceutical
      injection. Routine blood work and human anti-mouse antibody titers were
      monitored. Scintigraphic findings were compared with clinical parameters,
      prostatic fossa biopsy results and conventional imaging techniques. Except for
      transient hypotension in 1 subject following the second infusion, no side effects
      or human anti-mouse antibody titers were detected. In 22 subjects 1 or more
      lesions were detected, of which 11 (50%) were confirmed by biopsy, computerized
      tomography or magnetic resonance imaging. Of 14 subjects with lesions in the
      prostatic fossa 13 had biopsies performed, 8 (62%) of which were positive.
      Magnetic resonance imaging confirmed tumor in the spine and chest computerized
      tomography findings were compatible with lesions seen in the mediastinum in 1
      subject each. There was a statistically significant relationship between
      detecting a scan abnormality and the initial pathological stage of disease but
      not with the serum PSA. These data provide preliminary evidence that 111indium
      labeled CYT-356 can be safely administered and readministered, and it detects
      sites of occult prostate cancer recurrence in subjects whose PSA is increasing
      following radical prostatectomy.

PMID- 7523705
TI  - Effect of age, educational status, ethnicity and geographic location on prostate
      symptom scores.
AB  - We evaluated the effect of patient age, educational status, ethnicity and
      geographic location upon the American Urological Association benign prostatic
      hyperplasia symptom scores. Using patients attending Prostate Cancer Awareness
      Week, we collected additional data on the symptom score and also on education
      received. A total of 2,245 records was obtained from 4 different centers. Of the
      population 72% were white and 13% were black. Regression analysis of patient age
      versus symptom score demonstrated an increase with patient age from 4.59 at age
      40 years to 8.17 at age 70 years. Analysis of covariance revealed significant
      differences in age-adjusted scores between sites from 6.24 in New Orleans,
      Louisiana to 8.58 in Madison, Wisconsin. No effect was noted for education or
      ethnicity on symptom scores.

PMID- 7523706
TI  - Parameters of prostate volume and shape in a community based population of men 55
      to 74 years old.
AB  - Parameters of prostate volume and shape were determined in a community based
      population of 502 men 55 to 74 years old who had not undergone a previous
      prostate operation and did not suffer from prostatic cancer. The volumes of the
      total prostate and of the central relatively hypoechoic area of the prostate were
      determined. Of all men in this age range 95% had a total prostate volume of more
      than 20 cm3. Moderate correlations between age and both volume measurements were
      found (r = 0.26, p < 0.0001 and r = 0.34, p < 0.0001, respectively). The
      percentage increase per year of central hypoechoic volume (3.5%) was higher than
      that of total prostatic volume (2%). The average doubling time of total prostatic
      volume and volume of the central hypoechoic prostate was calculated to be 35 and
      20 years, respectively. The roundness of the prostate as expressed by width-to
      height ratio at the largest transverse section of the prostate correlated poorly
      with age (r = -0.13, p = 0.004). The average total prostate volumes as measured
      by transrectal ultrasound were 21 to 28% higher than reported average volumes
      measured at autopsy in men in the same age range.

PMID- 7523707
TI  - Accuracy of digital rectal examination and transrectal ultrasonography in
      localizing prostate cancer.
AB  - Not all prostate cancers are sonographically hypoechoic or palpable on digital
      rectal examination, and suspicious areas on transrectal prostatic ultrasonography
      or digital rectal examination often are not cancer. We present quadrant biopsy
      results from a multicenter prostate cancer screening study in which men were
      evaluated with prostate specific antigen (PSA) and digital rectal examination. If
      the PSA level was elevated (greater than 4.0 ng./ml., Hybritech Tandem assay) or
      digital rectal examination was suspicious quadrant biopsies were performed.
      Biopsy specimens were labeled separately, and histological findings were
      correlated by quadrant with the findings on ultrasonography and digital rectal
      examination. Of the 6,630 subjects enrolled into the study 16% were biopsied. Of
      1,002 quadrants that were suspicious on digital rectal examination 110 (11%) had
      cancer, while 308 of 418 quadrants containing cancer (74%) were not suspicious on
      digital rectal examination. Of 855 quadrants that were sonographically suspicious
      153 (18%) had cancer, while 282 of 435 quadrants containing cancer (65%) were not
      sonographically suspicious. Of 225 patients with cancer 137 (61%) would have been
      missed if only the exact site of the palpable induration had been biopsied. Of
      251 patients with cancer 131 (52%) would have been missed if only the exact site
      of the hypoechoic lesion had been biopsied. We conclude that digital rectal
      examination and transrectal ultrasonography have limited accuracy in identifying
      and localizing prostate cancer. Our study emphasizes the importance of obtaining
      systematic biopsies if the PSA level is elevated, even in the absence of digital
      rectal examination or ultrasound anomalies.

PMID- 7523708
TI  - Serum prostate specific antigen binding alpha 1-antichymotrypsin: influence of
      cancer volume, location and therapeutic selection of resistant clones.
AB  - We examined by gel filtration chromatography (Sephacryl 200) sera from 73
      untreated patients with peripheral zone prostatic cancer volumes of 1 to 17 cc as
      well as patients with clinical stages C and D2 cancer. We also examined the sera
      from 40 patients who had failed radiation or hormonal therapy to determine if
      clonal cell selection by these 2 therapies altered the binding of prostate
      specific antigen (PSA) to alpha 1-antichymotrypsin. Finally, we compared sera
      from 10 patients with benign prostatic hyperplasia (BPH) and 14 with large
      transition zone-BPH cancer. Without exception, of the total serum PSA recognized
      by the Hybritech Tandem-R, Yang Pros-Check, Abbott IMx and Ciba Corning ACS
      assays, 88 to 98% were complexed with alpha 1-antichymotrypsin in all cancer
      patients. The 10 patients with BPH showed less complexation (73 to 84%). These
      studies suggest that much of the quantitative differences among assays is
      determined more by relative differences in recognition of the free and complex
      forms of PSA than by calibration differences between assays.

PMID- 7523709
TI  - A comparison of 4 ultrasensitive prostate specific antigen assays for early
      detection of residual cancer after radical prostatectomy.
AB  - The Yang Pros-Check, Abbott IMx, Tosoh AIA-PACK PA and Nichols Institute
      reference laboratory prostate specific antigen (PSA) assays were compared in 30
      patients (138 sera) known to have no residual prostate cells. The mean + 3
      standard deviations of these sera was used to define a level of PSA that would
      indicate residual cancer. This residual cancer detection limit for each of the 4
      assays is 0.06, 0.01, 0.07 and 0.05 ng./ml., respectively, but the 0.01 level for
      the IMx assay is an artifact caused by setting the zero calibrator too high. All
      4 assays were then used to compare the number of days from radical prostatectomy
      to the detection of residual cancer in 23 cases (211 sera) that ultimately failed
      radical prostatectomy. The Yang, Tosoh and Nichols Institute assays were all
      similar, with an average of 569 to 589 days. The Abbott IMx assay was relatively
      insensitive in detecting the first appearance of PSA after radical prostatectomy
      (average 821 days) and it showed the earliest detection among the 4 assays in
      only 1 of 23 patients.

PMID- 7523710
TI  - Diagnosis of prostatic carcinoma: the yield of serum prostate specific antigen,
      digital rectal examination and transrectal ultrasonography.
AB  - Three tests are commonly used to diagnose prostate carcinoma to date: serum
      prostate specific antigen (PSA), digital rectal examination and transrectal
      ultrasonography. We evaluated these 3 tests in 1,001, 6-sector prostate needle
      biopsies to rule out prostate carcinoma. Of the biopsies 253 (25.3%) revealed
      prostate cancer. As a single test, PSA was superior to digital rectal examination
      or transrectal ultrasonography in predicting cancer in this patient population
      using difference of proportions tests. Receiver operating characteristic analysis
      also showed PSA to be the superior test. The combinations of PSA plus transrectal
      ultrasonography and PSA plus digital rectal examination were superior to digital
      rectal examination plus transrectal ultrasonography. We found cancer in 35 of 188
      patients (18.6%) with intermediate PSA levels of 4.1 to 10.0 ng./ml. and normal
      or asymmetric nonindurated rectal examinations. Only 5 of 79 patients (6.3%) with
      a normal digital rectal examination and PSA level of less than 4.0 ng./ml.
      demonstrated carcinoma on biopsy. Of the 5 patients 4 had annual increases in PSA
      of 40% or greater. While hypoechoic sectors were more than twice as likely as
      isoechoic sectors of the prostate to contain malignancy on biopsy, nearly 37.6%
      of the cancers were found in isoechoic sectors. A strategy of performing biopsy
      of only hypoechoic sectors would have misdiagnosed 24.6% of the patients with
      prostate cancer. We conclude that serum PSA is the most accurate of the 3
      diagnostic tests evaluated. We also recommend a systematic sextant biopsy
      technique.

PMID- 7523711
TI  - Histopathological changes in human prostatic adenoma following neodymium:YAG
      laser ablation therapy.
AB  - Transurethral laser ablation of the prostate is a procedure currently under
      evaluation as an alternative to transurethral resection of the prostate in the
      management of benign prostatic hyperplasia. Removal of prostatic tissue by
      endoscopic resection or open surgical techniques from 7 patients in whom
      prostatic laser ablation was previously attempted offered an opportunity to
      evaluate the sequential effects of such energy upon the human prostate at varying
      intervals after treatment. A progressive inflammatory and necrotic response,
      initially akin to that demonstrated after a thermal burn, together with evolving
      vascular changes within the residual viable prostatic tissue were demonstrated.
      Our study demonstrates the changes in the human prostate whereby neodymium:YAG
      laser energy causes a deep coagulative necrosis and arterial thrombosis in the
      prostatic adenoma. These changes differ significantly from those noted in canine
      studies. A slower cavitation effect is observed in the human compared with the
      canine, and this finding mirrors the continuing clinical improvement in voiding
      parameters with time.

PMID- 7523712
TI  - Re: The value of serial prostate specific antigen determinations 5 years after
      radiotherapy: steeply increasing values characterize 80% of patients.

PMID- 7523713
TI  - Re: The value of serial prostate specific antigen determinations 5 years after
      radiotherapy: steeply increasing values characterize 80% of patients.

PMID- 7523714
TI  - In vitro passive sensitization of guinea pig, rhesus monkey and human bladders as
      a model of noninfectious cystitis.
AB  - Studies of human bladder inflammation have been limited to examination of urine,
      bladder biopsy, or examination of autopsy material. We have developed an in vitro
      bladder passive sensitization technique which can measure type I responses of
      isolated human bladder tissue. We have compared these results using human tissue
      to those obtained with bladder tissue from guinea pigs and Rhesus monkeys. In our
      studies, bladder tissue was passively sensitized in vitro for 20 hours with
      immunoglobulin-containing serum. Subsequent antigen challenge of the passively
      sensitized tissue resulted in a time-dependent contraction that was accompanied
      by tissue histamine release. Contractions of guinea pig, monkey and human bladder
      tissue reached 79%, 100% and 78% of the maximal contraction induced by potassium
      chloride. In contrast, adjacent strips of unsensitized tissue had no detectable
      response to antigen challenge. The responses were reduced in the presence of
      histamine H1 receptor blockade with pyrilamine and abolished in the presence of a
      concomitant blockade of leukotriene synthesis with nordihydroguaiaretic acid
      (NDGA). Blockade of cyclooxygenase activity with indomethacin increased the
      contraction of the sensitized guinea pig bladder in response to antigen
      challenge. These findings demonstrate that in vitro passive sensitization of
      human bladder tissue can be used to investigate basic mechanisms of noninfectious
      bladder inflammation in humans.

PMID- 7523715
TI  - Basic fibroblast growth factor (FGF-2) in renal cell carcinoma, which is
      indistinguishable from that in normal kidney, is involved in renal cell carcinoma
      growth.
AB  - To investigate the role of basic fibroblast growth factor (FGF) in renal cell
      carcinoma growth, we have analyzed the expression of mRNA of basic FGF. In 7 of
      15 cases, basic FGF mRNA level in renal cell carcinoma tissues was higher than
      that in corresponding normal tissues. However, the tumor-to-normal ratios of
      expression levels are chiefly less than 2.0 and, in 5 cases, are even less than
      1.0. Furthermore, there was no correlation between the ratio and the clinical
      stage. In protein analysis, we could not find any difference between basic FGF
      extracted from renal cell carcinomas and that from normal kidney tissues in
      bioactivity, immunoreactivity, molecular weight and affinity to heparin. On the
      other hand, anti-basic FGF monoclonal antibody inhibited the growth of a renal
      cell carcinoma cell line, VMRC-RCW, and this inhibition was reversed by an
      extraphysiological amount of exogenous basic FGF (100 ng./ml.). These results
      suggest that basic FGF itself may have no pivotal role in renal cell carcinoma
      etiology but is involved in the growth of renal cell carcinomas in an autocrine
      manner.

PMID- 7523717
TI  - Prognostic factors and clinical significance of cancers detected by screening:
      growth rate and progression of prostate cancer.

PMID- 7523716
TI  - The use of prostate specific antigen for prostate cancer screening: a managed
      care perspective.
AB  - A large nonprofit staff model Health Maintenance Organization experienced
      increased use of prostate specific antigen (PSA) as a screening test for prostate
      cancer beginning in May 1991. A critical evaluation of the evidence in support of
      PSA screening was done and concluded that the use of PSA to screen for prostate
      cancer did not meet the criteria for an effective screening program. A guideline
      stating that PSA was not recommended as a screening test was implemented focusing
      on a model of shared decision making. PSA test ordering decreased significantly
      when patients were fully informed about the evidence for PSA screening. If PSA
      screening had continued at the peak rate, the cascade of intervention initiated
      by screening would have resulted in significant complications and approximately
      $4,800,000 in increased costs.

PMID- 7523718
TI  - The pathological features and prognosis of prostate cancer detectable with
      current diagnostic tests.
AB  - The discrepancy between the high prevalence of prostate cancer found at autopsy
      and the low incidence of clinical cancer prompted a study to determine whether
      the new diagnostic tests, that is ultrasonography and serum prostatic specific
      antigen (PSA) levels, detect prostate cancer at an earlier stage than the
      traditional test, digital rectal examination, without detecting a larger
      proportion of clinically unimportant cancer. Clinically detected cancer treated
      by radical prostatectomy (306 cases) and incidental cancer found in
      cystoprostatectomy specimens (90) were categorized into 3 groups by the volume,
      grade, extent of the cancer and outcome of treatment: clinically unimportant
      tumor (0.5 cm.3 or less, Gleason grades 1 to 3 and confined to the prostate),
      clinically important curable cancer (more than 0.5 cm.3 or grade 4 or 5 and
      confined, or with microscopic extracapsular extension) or advanced disease
      (extensive extracapsular extension, seminal vesicle invasion or lymph node
      metastases). Of 306 clinically detected tumors 9% were unimportant and 29% were
      advanced. In contrast, incidental cystoprostatectomy disease was either
      unimportant (78%) or curable (22%) and no tumor was advanced (p < 0.0005). Cancer
      detectable by digital rectal examination, ultrasonography or PSA was distributed
      similarly among the 3 groups. Impalpable cancer detected by PSA was less likely
      to be advanced (11%) than cancer detected by digital rectal examination (34%, p =
      0.01) but no more likely to be unimportant (13% versus 8%). Of 29 tumors detected
      only by systematic biopsies because of an elevated PSA level only 4% were
      advanced, while 17% were unimportant. Cancer detectable with each of the
      available diagnostic tests was similar and differed distinctly from that found
      incidentally in cystoprostatectomy specimens. The detection of impalpable cancer
      by PSA or ultrasound decreased the proportion of advanced tumor detected without
      increasing significantly the detection of unimportant disease.

PMID- 7523719
TI  - Radical prostatectomy for impalpable prostate cancer: the Johns Hopkins
      experience with tumors found on transurethral resection (stages T1A and T1B) and
      on needle biopsy (stage T1C).
AB  - We review the pathological findings of impalpable prostate cancer detected by
      transurethral resection (stages T1a and T1b) and needle biopsy (stage T1c). The
      short-term (4 years) and long-term (8 to 10 years) natural histories of untreated
      stage T1a prostate cancer are examined, as are options to follow patients
      expectantly. The findings on radical prostatectomy for stages T1a and T1b disease
      are reviewed and compared. Of the 64 cases of stage T1a disease 13 (20%) showed
      substantial tumor, including 7 with more than 1 cc of tumor, 5 with capsular
      penetration and 1 with a Gleason grade 4 + 5 = 9 tumor. Based on preoperative
      pathological parameters, one could not predict which cases had minimal versus
      substantial tumor. In a study from our institution that undertook complete
      histological examination of 39 radical prostatectomy specimens of stage T1b
      carcinoma, we found that all prostates contained residual carcinoma, 26% had
      capsular penetration and 10% had invasion of the seminal vesicles. When comparing
      morphometrically determined volumes of carcinoma with similar data from 56
      patients with stage T2 carcinoma, stage T1b tumors were much more heterogeneous
      in grade, location and volume than were stage T2 lesions. Unless all 3 variables
      (grade, volume and location) were known, the final pathological stage of T1b
      cancers could not be predicted with confidence. Finally, we examined preoperative
      clinical and pathological parameters in 157 men with clinical stage T1c disease
      undergoing radical prostatectomy, and correlated these findings with pathological
      extent of disease in the surgical specimen in an attempt to identify a subset of
      patients with potentially biologically insignificant tumor who might be followed
      conservatively. Of the tumors 16% were insignificant (less than 0.2 cc, organ
      confined and Gleason grade less than 7), 10% were minimal (0.2 to 0.5 cc, organ
      confined and Gleason grade less than 7), 37% were moderate (more than 0.5 cc or
      capsular penetration with Gleason sum less than 7) and 37% were advanced
      (capsular penetration with Gleason sum 7 or more, or positive margins, positive
      seminal vesicles or positive lymph nodes). These findings are intermediate
      between those found in clinical stages T1a and T2 disease. The best model
      predicting insignificant tumor was a prostate specific antigen (PSA) density of
      less than 0.1 and no adverse pathological finding on needle biopsy or PSA density
      of 0.1 to 0.15 with less than 3 mm. low to intermediate grade cancer on only 1
      needle biopsy core. The positive predictive value of the model was 95% with a
      negative predictive value of 66%.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523721
TI  - Characteristics of prostate cancer detected in the American Cancer Society
      National Prostate Cancer Detection Project.
AB  - The American Cancer Society-National Prostate Cancer Detection Project is a
      prospective, comparative study of a cohort of 2,999 men 55 to 70 years old not
      suspected on entry of having prostate cancer. A total of 164 prostate cancers is
      available from this project for analysis. A small proportion of tumors detected
      were advanced in terms of the clinical stage at diagnosis. Cancer detected by
      digital rectal examination tended to be more advanced than that found on the
      basis of only transrectal ultrasound or prostate specific antigen (PSA). A large
      proportion of patients received curative therapy involving radical prostatectomy
      in 67.1% and radiotherapy in 18.3%. Of 103 men presumed to have organ confined
      disease and treated by prostatectomy 64 (37.9%) actually had locally extensive
      cancer pathologically. PSA level and PSA density were associated with the
      detection of organ confined cancer but several advanced tumors had PSA levels in
      the normal range. Age referenced PSA, compared to conventional standards,
      demonstrated lower sensitivity to cancer with little improvement in specificity.
      The disease resulting from this multimodality detection effort represented a
      spectrum of pathological conditions. Further followup and evaluation are needed
      to determine whether these benefits are reflected in long-term mortality and
      survival experience.

PMID- 7523720
TI  - The nature of prostate cancer detected through prostate specific antigen based
      screening.
AB  - Prostate specific antigen (PSA) based screening nearly doubles the detection rate
      of early prostate cancer. However, it is unknown whether the additional tumors
      detected are medically important. Traditional clinical and pathological features
      associated with medically important cancer include a palpable tumor, multifocal
      or diffuse involvement and moderately or poorly differentiated histology. In
      contrast, microfocal, well differentiated tumors are considered to be possibly
      medically unimportant. We sought to examine the clinical and pathological tumor
      stage and tumor grade in 1,169 consecutive men whose prostate cancer was detected
      during serial PSA based screening protocols involving 24,346 men screened at 6
      month intervals. Of the patients 97% had clinically localized (clinical stage T1
      or T2) tumors, of which 39% were not palpable (stage T1). Of the men whose cancer
      was detected through initial screening who underwent surgical staging 69% had
      pathologically organ confined (pathological stage whose cancer was detected
      through initial screening pT1 or pT2) disease compared to 74% whose cancer was
      detected through serial screening (after an initially negative screening).
      Impalpable, clinically focal, well differentiated minimal tumors were noted in
      16% of the men. However, only 3% of the men who underwent surgical staging had
      impalpable, pathologically microfocal, well differentiated minimal tumors. We
      conclude that the majority of tumors detected through PSA based screening have
      the clinical and pathological features associated with medically important
      prostate cancer.

PMID- 7523722
TI  - Natural history of changes in prostate specific antigen in early stage prostate
      cancer.
AB  - Until recently, the only information on the growth rate of prostate tumors has
      been derived from cross-sectional histological labeling studies, autopsy data and
      clinical studies of patients managed expectantly. However, serial measurements of
      prostate specific antigen (PSA) may now allow studies of the natural history of
      the earliest stages of prostate cancer. Frozen sera samples from the Baltimore
      Longitudinal Study of Aging have been used to compare the patterns of change in
      PSA levels in men with and without prostate cancer up to 25 years before the
      diagnosis of cancer. Men with no prostatic disease exhibited a slow linear
      increase in PSA levels, whereas benign prostatic hyperplasia cases showed a
      gradual acceleration in the rate of change in PSA. In contrast, cancer cases
      exhibited an early linear phase followed by an exponential phase of increase in
      PSA levels before diagnosis. On average, the exponential phase of PSA increases
      began 7 to 9 years before the tumors were detected clinically. Thus, there is a
      significant window of opportunity for early detection of prostate cancer. The
      changes in PSA observed in men with and without prostate cancer are consistent
      with available information on prostatic growth and the long natural history of
      prostate cancer. A better understanding of the various factors that affect serum
      PSA levels may allow more effective use of PSA measurements to detect early stage
      tumors and predict the biological potential of a tumor.

PMID- 7523723
TI  - Deferred treatment of clinically localized low grade prostate cancer: the
      experience from a prospective series at the Karolinska Hospital.
AB  - From 1978 to 1982, 172 patients with stages T1 to 3NxM0 prostate cancer were
      included in a surveillance protocol with deferred treatment on symptomatic
      progression. Median patient age at diagnosis was 68 years (range 38 to 89 years).
      Mean followup was 80 +/- 32 months. Of the patients 58% had local and 19% had
      distant progression, and 52% had received treatment at followup. Disease specific
      survival rate at 10 years was 80% for the total series, 84% for the subgroup with
      stage T1 or T2 tumor and 92% for those with stage T1 or T2 tumor who were less
      than 70 years old at diagnosis. For the subgroup with stage T3 tumor the disease
      specific survival rate at 9 years was 70%. In all subgroups the competing
      mortality rate was higher than the prostate cancer mortality rate. Deferred
      treatment appears to be an acceptable option for patients with tumor clinically
      confined to the prostate and a life expectancy of 10 years or less.

PMID- 7523724
TI  - Early prostate cancer: the national results of radiation treatment from the
      Patterns of Care and Radiation Therapy Oncology Group studies with prospects for
      improvement with conformal radiation and adjuvant androgen deprivation.
AB  - Long-term outcome of the Patterns of Care Study and the Radiation Therapy
      Oncology Group are used to demonstrate the national average results of treating
      early prostate cancer in the United States. A group of patients with stage T1B2
      disease and pathologically negative lymph nodes showed excellent 10-year survival
      rates and freedom from clinical evidence of disease, while prostate specific
      antigen (PSA) correlations in 10-year survivors indicate that 88% were clinically
      free of cancer and had a PSA level of less than 4.0 mg./nl., and 65% had a PSA
      level of less than 1.5 ng./ml. The latter group represented clinical and
      biochemical cures. The improvement noted in outcome of locally advanced prostate
      cancer treatment by Radiation Therapy Oncology Group prospective trials combining
      androgen deprivation and radiation therapy is presented. These trials will be
      extended to the poor prognosis group with stage T1,2 disease. The advantages of
      conformal therapy in acute and late morbidity are illustrated with preliminary
      evidence of improved PSA response as a result of improved technique and higher
      dose associated with conformal 3-dimensional treatment.

PMID- 7523725
TI  - Prostate specific antigen as an outcome variable for T1 and T2 prostate cancer
      treated by radiation therapy.
AB  - Between 1987 and 1991, 269 patients with clinical stage T1 or T2, N0 or Nx
      adenocarcinoma of the prostate underwent external beam radiation therapy as the
      sole initial treatment and were followed with serial prostate specific antigen
      (PSA) levels for 9 to 73 months (mean 33, median 30). Of the patients 26 had
      clinical evidence of disease relapse, 58 had an increasing PSA profile and 62 had
      either relapse or an increasing PSA. The actuarial incidence of increasing PSA
      was 30% at 5 years and the incidence of relapse or increasing PSA was 36% at the
      same time. With relapse or increasing PSA level as an end point, pretreatment PSA
      level, Gleason grade and serum prostatic acid phosphatase level were individually
      significant covariates. However, in multivariate analysis only pretreatment PSA
      level was significant. The 5-year actuarial rates of relapse or increasing PSA
      according to pretreatment PSA level were 4 ng./ml. or less-14%, greater than 4 to
      10 ng./ml.-33%, greater than 10 to 30 ng./ml.-55% and greater than 30 ng./ml.
      greater than 80%. Post-irradiation PSA levels at 3 and 6 months provided
      prognostic information additional to that inherent before treatment. However, the
      nadir PSA value, achieved typically at 6 to 12 months, was the most significant
      aspect of posttreatment PSA. Patients with a nadir PSA level of less than 1
      ng./ml. fared well, with a 12% incidence of relapse or increasing PSA at 5 years.
      Nadir values exceeding 1 ng./ml. were associated with an increasing relapse rate
      as the nadir value increased, and nearly two-thirds of the cases in which the
      nadir exceeded 4 ng./ml. failed by 2 years. When increasing PSA was used as an
      end point additional to relapse, the outcome in this series was significantly
      worse than in an earlier series evaluated without PSA. Comparing these 2 series
      resulted in an estimate that PSA begins to increase approximately 4 to 5 years
      before the appearance of clinically overt disease. These results reveal the high
      significance of pretreatment PSA levels, significance of nadir PSA values after
      treatment, earlier detection of persistent disease by the increasing PSA profile,
      and the fact that total and permanent eradication of localized prostate cancer is
      considerably more difficult than traditionally believed. The therapeutic
      implications of this series, and the implications on the quantity and quality of
      patient lives await prospective study.

PMID- 7523726
TI  - Radical prostatectomy and radical radiation therapy for clinical stages T1 to 2
      adenocarcinoma of the prostate: new insights into outcome from repeat biopsy and
      prostate specific antigen followup.
AB  - Assessment of outcome following radical treatment for stages T1 to T2 prostate
      cancer has become more sensitive and rapid with the use of serum prostate
      specific antigen (PSA) in routine followup. PSA has identified substantially more
      failure following all radical therapies than was previously detected in series
      using clinical end points. Furthermore, it has also allowed a better assessment
      of the biological potential of histologically evident residual disease, that is a
      positive surgical margin after prostatectomy or positive repeat biopsy 2 years
      after radiation. Both situations are associated with subsequent biochemical
      failure in the majority of patients. The stages T1 to T2 cancer group is
      extremely heterogenous. In the few series with PSA followup that have evaluated
      long-term (greater than a decade) outcome for this group some report cure rates
      well below 40% for surgery and radiation. When comparing the results of any
      radical treatment series (surgery versus surgery and radiation versus radiation,
      as well as radiation versus surgery) selection may have a crucial role in
      predicting outcome. Surgical series tend to contain more patients with stages T1
      to T2a tumors of low grade who have low initial PSA values and are known to have
      negative nodes. These patients, when treated with radical radiation, also have a
      favorable prognosis. It is hoped that the introduction of screening programs will
      improve outcome through earlier disease detection.

PMID- 7523727
TI  - National patterns of prostate cancer treatment by radical prostatectomy: results
      of a survey by the American College of Surgeons Commission on Cancer.
AB  - To evaluate the patterns of use of radical prostatectomy for the treatment of
      prostate cancer in the United States, the American College of Surgeons Commission
      on Cancer in association with the American Cancer Society and American Urological
      Association surveyed 484 institutions concerning 2,122 patients treated in 1990.
      The results revealed that 93% of the patients were younger than 75 years when
      treated. Pretreatment prostate specific antigen level was greater than 4.0
      ng./ml. in 85.4% of the patients. Surgical-pathological evaluation showed that
      57.5% of the patients treated had American Joint Committee on Cancer pathological
      stages O, I and II corresponding to American Urological Association stages A1 to
      B2. Positive pathological findings, for example microscopic tumor extension or
      invasion, were associated with elevated prostate specific antigen levels at
      followup. The mortality rate associated with the operation was 0.7%. Impotence
      following treatment was observed in 56.6% of the patients who were potent
      preoperatively and complete incontinence was reported in 3.6% of the patients who
      were previously continent. The data may provide benchmarks by which further
      trends in prostate cancer treatment may be compared.

PMID- 7523728
TI  - The incidence and significance of detectable levels of serum prostate specific
      antigen after radical prostatectomy.
AB  - A total of 601 patients who underwent radical retropubic prostatectomy for
      localized prostate cancer at our institution was followed with serial prostatic
      specific antigen (PSA) determinations. Three separate groups were delineated by
      pathological stage: 293 patients with organ confined disease, 215 with
      involvement of the capsule or positive margins and 93 with extension to the
      seminal vesicles. Followup ranged from 12 to 237 months (median 34). Five and 10
      year disease-free survival rates for the 601 patients were 86 +/- 2% and 78 +/-
      3%, respectively. The rate of detectable PSA (greater than 0.4 ng./ml.), used as
      an indicator of cancer progression, revealed 5 and 10-year disease-free rates of
      69 +/- 2% and 47 +/- 3%, respectively. When comparing the patients from an
      earlier series to those who underwent surgery after 1986, an improvement in the 5
      year clinical disease-free rate was noted (78 +/- 2% versus 93 +/- 2%,
      respectively). Similarly, an improvement in the 5-year disease-free survival rate
      with nondetectable PSA level was demonstrated in our contemporary series (80 +/-
      3%) compared to our historical series. Of the 601 patients 123 had a detectable
      post-prostatectomy PSA level with or without clinical evidence of metastasis. A
      PSA doubling time before onset of adjuvant therapy was determined in 94 patients.
      Post-prostatectomy PSA doubling times were significantly different when comparing
      the patients who ultimately had progression to distant metastases (median 4.3
      months) to those with either clinical local recurrence or a PSA elevation as the
      sole indicator of recurrence (median 11.7 months). Radical retropubic
      prostatectomy, whether assessed by clinical or biochemical means, has
      demonstrated excellent disease-free survival rates, especially since the advent
      of PSA and anatomical radical prostatectomy.

PMID- 7523729
TI  - Impact of radical prostatectomy in the management of clinically localized
      disease.
AB  - The cancer specific death rate following radical prostatectomy in patients with
      organ confined and specimen confined disease was 10% at 13.5 years, less than the
      noncancer death rate of 20% for patients in these disease extent categories. The
      median age of all patients in these categories was 65 years. Cancer remains the
      dominate cause of death in patients with margin-positive disease, being 40% at
      13.5 years. Disease detected by prostate specific antigen (PSA) rather than
      digital rectal examination appears to be of smaller volume and to have a higher
      probability of negative margins. Data argue that early detection of PSA will
      shift patients to a more favorable disease category at surgical intervention.
      Disease recurrence or persistence by PSA detection seems to precede clinical
      detection of disease by 3 to 5 years. Disease recurrence by PSA detection does
      not predict survival outcome, probably does not differentiate between local and
      distant microscopic recurrence, and is not predictive of biological
      aggressiveness.

PMID- 7523730
TI  - Cancer control and quality of life following anatomical radical retropubic
      prostatectomy: results at 10 years.
AB  - The experience after 10 years with anatomical radical retropubic prostatectomy at
      The Johns Hopkins Hospital is reviewed. Between April 1982 and March 1991, 955
      men with clinically localized prostate cancer (clinical stages T1 to T2)
      underwent staging pelvic lymphadenectomy and anatomical radical retropubic
      prostatectomy. Using actuarial analysis, at 10 years the likelihood of an
      undetectable prostate specific antigen (PSA) level was 70%, isolated elevation of
      PSA 23%, distant metastases 7% and local recurrence 4%. The actuarial likelihood
      of an elevated serum PSA increased with increasing pathological stage: the 10
      year likelihood of freedom from PSA relapse was 85% for men with organ confined
      disease, 82% with focal capsular penetration, 54% with established capsular
      penetration and Gleason score 2 to 6 disease, 42% with established capsular
      penetration and Gleason score 7 to 10 disease, and 43% with seminal vesicle
      involvement. These data indicate that radical prostatectomy cures the majority of
      men with organ confined disease or with well to moderately well differentiated
      tumors that have penetrated the prostatic capsule to the extent where it is
      possible to obtain a clear surgical margin. Radical prostatectomy should be
      reserved for patients who can be cured and who will live long enough to benefit
      from it. These are also the patients who have the best quality of life
      postoperatively.

PMID- 7523731
TI  - 5-year tumor recurrence rates after anatomical radical retropubic prostatectomy
      for prostate cancer.
AB  - The new anatomical approach to radical retropubic prostatectomy with its nerve
      sparing option allows for preservation of erections, improved urinary continence,
      decreased blood loss, and lower operative mortality and morbidity rates. We
      sought to evaluate cancer control with this operation by determining the 5-year
      tumor recurrence rates using detectable serum prostate specific antigen levels as
      a criterion for tumor recurrence in a series of 925 consecutive men with clinical
      stage T1 or T2 prostate cancer. Overall, the 5-year probability of nonprogression
      was 78% (95% confidence limits 74 to 82%). The 5-year nonprogression rate was
      higher in patients whose tumors were not palpable (90% for impalpable tumors
      detected through transurethral resection of the prostate, 97% for impalpable
      prostate specific antigen detected tumors and 74% for palpable tumors).
      Nonprogression correlated with pathological tumor stage (91% for organ confined
      disease, 74% for positive margins or microscopic capsular perforation, 32% for
      seminal vesical invasion and virtually nil for lymph node metastases) and tumor
      grade (89% for well, 78% for moderately and 51% for poorly differentiated
      tumors). We conclude that anatomical radical prostatectomy achieves excellent
      cancer control for patients with organ confined prostate cancer.

PMID- 7523732
TI  - Can radical prostatectomy alter the progression of poorly differentiated prostate
      cancer?
AB  - A favorable outcome after radical prostatectomy for early stage prostate cancer
      has sometimes been attributed to the relatively benign natural history of the
      disease rather than the beneficial effects of treatment. Poorly differentiated
      tumors, however, are recognized as inherently aggressive and progress rapidly
      when managed conservatively. We determined the actuarial rate of treatment
      failure after radical prostatectomy for clinically localized (stages T1 to T3)
      poorly differentiated cancer, using as an end point an increase in the serum
      level of prostate specific antigen (PSA) to assess whether treatment altered the
      rapid progression expected of these cancers. Of 500 patients treated with radical
      prostatectomy, regardless of grade, the actuarial nonprogression rate was 76 +/-
      5% at 5 years and 73 +/- 6% at 10 years. Poorly differentiated cancer, defined as
      Gleason score 7 or greater in the radical prostatectomy specimen, was present in
      268 patients (54%) who had a nonprogression rate at 5 years of 55 +/- 12%
      compared to 92 +/- 4% for the 232 patients with a well or moderately
      differentiated (Gleason score less than 7) cancer (p < 0.00005). The extent of
      the cancer (confined or not confined) was strongly associated with progression (p
      < 0.00005). Only 76 of the 268 poorly differentiated tumors (28%) were confined
      to the prostate and the prognosis was excellent. At 5 years 85 +/- 18% of the
      patients had no evidence of progression, compared to 46 +/- 12% with poorly
      differentiated cancer extending outside the gland (p < 0.0001). In a multivariate
      analysis neither the grade nor volume of the tumor influenced the rate of
      progression when the cancer was confined to the prostate. Impalpable tumors
      detected by an elevated PSA level were as likely to be poorly differentiated as
      palpable disease (56% versus 63%) but were significantly more likely to be
      confined to the prostate (44% versus 24%, p < 0.01). Poorly differentiated
      cancers usually extend outside of the prostate by the time they are detected, and
      they progress rapidly. PSA increases the detection of impalpable high grade
      cancer confined to the gland. When these tumors are detected while still
      confined, most can be controlled by radical prostatectomy.

PMID- 7523733
TI  - Long-term (15 years) results after radical prostatectomy for clinically localized
      (stage T2c or lower) prostate cancer.
AB  - To provide information about long-term outcome after radical prostatectomy for
      clinically localized prostatic cancer (stage T2c or lower), we undertook a
      retrospective analysis of 3,170 consecutive patients (mean age 65.3 +/- 6.4
      years, range 31 to 81) with a mean followup of 5 years. Complication rates for
      patients who underwent prostatectomy before 1988 were compared with those who
      underwent radical prostatectomy more recently. Of the patients 49 (1.5%), 178
      (5.6%), 897 (28%) and 2,047 (65%) had clinical stages T1a, T1b, T2a and T2b,c
      disease, respectively. The Gleason score was 3 or less in 292 patients (9%) and 7
      or greater in 782 (25%). Overall, 438 patients (14%) died, 159 (5%) of cancer.
      The crude 10 and 15-year survival rates for all patients were 75% and 60%,
      respectively, which is comparable to the expected survival of a control group
      (67% and 46%). The cause specific survival rates were 90% and 82%, respectively,
      metastasis-free survival rates 82% and 76%, local recurrence-free survival rates
      83% and 75%, overall recurrence-free rates 72% and 61%, and overall recurrence
      plus prostate specific antigen progression-free (greater than 0.2 ng./ml.) rates
      52% and 40%, respectively. Clinical stage did not significantly affect survival
      but tumor grade was associated: 10 and 15-year cause specific survival rates were
      95% and 93%, respectively, for a Gleason score of 3 or less, 90% and 82%,
      respectively, for a score of 4 to 6, and 82% and 71%, respectively, for a score
      of 7 or more. Of all patients 26% received adjuvant treatment (hormonal and/or
      radiation) within 3 months postoperatively because of advanced local pathological
      stage (pT3 or higher) or margin positive disease. The 30-day mortality rate was
      0.3% (0% for 1,728 patients who underwent surgery in 1988 or later). Only 1
      patient in the 70 year or older age group died during hospitalization.
      Complications decreased with time. In a contemporary group the complications were
      rectal injury in 0.6% of the patients, colostomy in 0.06%, myocardial infarction
      in 0.4%, deep venous thrombosis in 1.1%, pulmonary embolism in 0.7% and total
      urinary incontinence (3 or more pads per day) in 0.8%. Recent intraoperative
      blood loss was a median of 600 ml., and the incidence of recent need for any
      transfusion was 31% and it is presently less than 5%. In this series patients
      undergoing radical prostatectomy for clinically localized prostate cancer were
      usually healthy and, thus, had low co-morbidity. Survival rates at 10 and 15
      years compare favorably with those of an age-matched control group.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7523734
TI  - Cost analyses of prostate cancer screening: frameworks for discussion.
      Investigators of the American Cancer Society-National Prostate Cancer Detection
      Project.
AB  - Our recent cost analysis of prostate cancer early detection evaluated the
      economic performance of various prostate specific antigen (PSA) screening
      approaches, detected marginal cost variations with time and used a benefit-cost
      calculation as a framework for further discussion. Receiver operator
      characteristic analysis initially suggested an optimal test performance for PSA
      of 2 to 3 ng./ml. when used alone and at approximately 3 ng./ml. in combination
      with digital rectal examination. However, lower PSA decision levels require cost
      justifications. Marginal cost analysis demonstrated markedly decreased use of
      digital rectal examination by year 3 due to significantly lower sensitivity for
      incident cancer. The benefit-cost equation acknowledges that many parameters of
      cost and probability are not definitive to date yet illustrated major points for
      discussion. The cost parameters most sensitive to incremental change in
      decreasing order are the specificity of the screening test, benefits obtained
      from early therapy and prevalence of the disease. Discussions about improving the
      likelihood of overall benefit for the United States population should focus on
      these parameters, as well as social and ethical implications. If we assume
      minimized future expenditures for terminal cancer care via decreases in therapy
      choices or coverage, no economic benefit for screening exists. If we also assume
      that potential costs to society are not roughly approximated by any benefits, we
      may engender inappropriate attempts at cost reduction by effectively discouraging
      screening in the highest risk groups. Perhaps the greatest immediate cost control
      issue is the marked increase in prostate cancer detection in the oldest age
      groups who have the least likelihood of mortality or morbidity benefits. Current
      cost savings may be possible with improved public health education about the
      appropriateness of early detection in the oldest age groups or those with
      significant preexisting medical conditions.

PMID- 7523735
TI  - Prostate cancer screening in the prostate, lung, colorectal and ovarian cancer
      screening trial of the National Cancer Institute.
AB  - Screening for prostate cancer and subsequent treatment is of unknown benefit but
      carries known treatment related morbidity and mortality risks. The recent
      enthusiasm for screening in the United States contrasts sharply with the more
      cautious attitudes of the European and Canadian medical communities. Current data
      from screening series without randomization and controls are inadequate to
      determine screening benefit. The prostate, lung, colorectal and ovarian cancer
      (randomized, controlled) screening trial of the National Cancer Institute, to
      include 74,000 men (and 74,000 women) 60 to 74 years old, has a design power of
      90% to determine a 20% reduction of prostate cancer mortality from a baseline and
      3 subsequent annual screens using prostate specific antigen and digital rectal
      examination. Randomization of participants into this trial began on November 16,
      1993. Ten screening centers nationwide, a coordinating center, a laboratory and a
      biorepository are participating under contract.

PMID- 7523736
TI  - The Prostate Cancer Intervention Versus Observation Trial: a randomized trial
      comparing radical prostatectomy versus expectant management for the treatment of
      clinically localized prostate cancer.
AB  - The Prostate Cancer Intervention Versus Observation Trial (PIVOT) is a randomized
      controlled trial sponsored by the Department of Veterans Affairs and the National
      Cancer Institute. PIVOT will enroll 2,000 participants from at least 80 Veterans
      Administration and National Cancer Institute medical centers. The purpose of
      PIVOT is to determine which of 2 strategies is superior for managing clinically
      localized prostate cancer (stage T1/T2NXM0) of all histological grades. Patients
      less than 75 years old will be randomized to either radical prostatectomy with
      early intervention for disease persistence/recurrence or expectant management
      with palliative therapy reserved for symptomatic or metastatic disease
      progression. Participants will be excluded if they have received prior therapy
      for prostate cancer (except transurethral resection of the prostate) or are
      judged not to be candidates for radical prostectomy. All patients with newly
      diagnosed prostate cancer will be recorded on the PIVOT screening log. Registry
      information will include patient age, race, prostate specific antigen level,
      clinical stage, histological tumor grade, initial therapy, and vital status.
      Patients meeting eligibility criteria will watch an information and randomization
      video tape developed for PIVOT. Participants will be randomized over a 3-year
      period and followed for a minimum of 12 years. Data collected at followup will
      include urological symptoms, disease and treatment related morbidity, and disease
      specific and overall quality of life. Evidence of symptomatic or asymptomatic
      disease persistence, recurrence or progression will be measured by questionnaire,
      physical examination, digital rectal examination, prostate specific antigen and
      annual bone scan. The primary study end point will be all cause mortality.
      Secondary outcomes will include prostate cancer and treatment specific morbidity
      and mortality rates, health status, predictors of disease specific outcomes and
      cost-effectiveness. PIVOT will provide a 90% power to detect a 15% relative
      decrease in all cause mortality and a 35% relative decrease in prostate cancer
      specific mortality rate by either treatment strategy.

PMID- 7523737
TI  - Artificial neural networks in the diagnosis and prognosis of prostate cancer: a
      pilot study.
AB  - There is controversy about how prostate cancer screening tests should best be
      used because of the false-negative and false-positive results. There also is
      controversy about prostate cancer treatment because of errors in tumor staging,
      uncertainty about treatment efficacy and the variable natural history of the
      disease. We sought to determine in a pilot study whether artificial neural
      networks would be helpful to predict biopsy results in men with abnormal
      screening test(s) and to predict treatment outcome after radical prostatectomy.
      To predict biopsy results, we extracted data from a prostate specific antigen
      (PSA) based screening study data base in 1,787 men with a serum PSA concentration
      of more than 4.0 ng./ml. (approximately 40% of the men also had suspicious
      findings on digital rectal examination). To predict cancer recurrence after
      radical prostatectomy, we extracted data from a random sample of 240 patients
      selected from a data base of men who had undergone radical prostatectomy. The
      neural network predicted the biopsy result with 87% overall accuracy, and its
      output threshold could be adjusted to achieve the desired tradeoff between
      sensitivity and specificity. It also predicted tumor recurrence with 90% overall
      accuracy. We conclude that trained neural networks may be useful in decision
      making for prostate cancer patients.

PMID- 7523738
TI  - From the Food and Drug Administration.

PMID- 7523739
TI  - Methotrexate and misoprostol vs misoprostol alone for early abortion. A
      randomized controlled trial.
AB  - OBJECTIVE: To compare the safety and efficacy of early abortion by administration
      of methotrexate and misoprostol vs administration of misoprostol alone. DESIGN:
      Randomized controlled trial. SETTING: San Francisco (Calif) General Hospital.
      PATIENTS: Pregnant women at 56 days' gestation or less seeking elective abortion.
      Sixty-three women volunteered for the trial; 61 completed the study and are
      included in the analysis. INTERVENTION: Intramuscular administration of 50 mg of
      methotrexate per square meter of body surface area followed 3 days later by
      vaginal administration of 800 micrograms of misoprostol (group 1) or the same
      dose of misoprostol given alone (group 2). The misoprostol dose was repeated 24
      hours later if abortion had not occurred. MAIN OUTCOME MEASURES: Successful
      abortion, duration of vaginal bleeding, side effects, and change in beta-human
      chorionic gonadotropin (beta-hCG) level. An abortion was considered successful if
      the pregnancy ended without requiring a surgical procedure. RESULTS: Complete
      abortion occurred in 28 (90%) of 31 patients in group 1 and 14 (47%) of 30
      patients in group 2 (P < .001). Seventeen (61%) of the 28 women in group 1 who
      aborted did so the same day as misoprostol administration; vaginal bleeding
      lasted a mean (+/- SD) of 10 (+/- 4) days, and beta-hCG level was less than or
      equal to 10 IU/L by a mean of 31 (+/- 6) days after methotrexate administration.
      The 11 other women in group 1 who aborted did so after a mean delay of 29 (+/-
      11) days; vaginal bleeding lasted 7 (+/- 4) days, and beta-hCG level was less
      than or equal to 10 IU/L by a mean of 24 (+/- 11) days after the abortion. There
      were three treatment failures in group 1: two ongoing pregnancies (6%) and one
      incomplete abortion (3%). For the 14 women with successful abortions in group 2,
      vaginal bleeding lasted a mean of 10 (+/- 6) days and beta-hCG level was less
      than or equal to 10 IU/L by mean of 39 (+/- 18) days after the misoprostol. There
      were 16 treatment failures in group 2: eight ongoing pregnancies (27%), and eight
      incomplete abortions (27%). Methotrexate side effects were minimal. Misoprostol
      side effects were diarrhea in 18% and nausea and vomiting in 5%. CONCLUSIONS:
      Methotrexate and vaginal misoprostol are more effective than misoprostol alone.
      Both drugs are available throughout the United States, and both drugs are
      inexpensive. This combination may offer an alternative to the use of
      antiprogestin and prostaglandin for medical abortion.

PMID- 7523741
TI  - From the Centers for Disease Control and Prevention. Certification of
      poliomyelitis eradication--the Americas, 1994.

PMID- 7523740
TI  - Comfort care for terminally ill patients. The appropriate use of nutrition and
      hydration.
AB  - OBJECTIVE: To determine the frequency of symptoms of hunger and thirst in a group
      of terminally ill patients and determine whether these symptoms could be
      palliated without forced feeding, forced hydration, or parenteral alimentation.
      DESIGN: Prospective evaluation of consecutively admitted terminally ill patients
      treated in a comfort care unit. SETTING: Ten-bed comfort care unit in a 471-bed
      long-term care facility. PARTICIPANTS: Mentally aware, competent patients with
      terminal illnesses monitored from time of admission to time of death while
      residing in the comfort care unit. MAIN OUTCOME MEASURES: Symptoms of hunger,
      thirst, and dry mouth were recorded, and the amounts and types of food and fluids
      necessary to relieve these symptoms were documented. The subjective level of
      comfort was assessed longitudinally in all patients. RESULTS: Of the 32 patients
      monitored during the 12 months of study, 20 patients (63%) never experienced any
      hunger, while 11 patients (34%) had symptoms only initially. Similarly, 20
      patients (62%) experienced either no thirst or thirst only initially during their
      terminal illness. In all patients, symptoms of hunger, thirst, and dry mouth
      could be alleviated, usually with small amounts of food, fluids, and/or by the
      application of ice chips and lubrication to the lips. Comfort care included use
      of narcotics for relief of pain or shortness of breath in 94% of patients.
      CONCLUSIONS: In this series, patients terminally ill with cancer generally did
      not experience hunger and those who did needed only small amounts of food for
      alleviation. Complaints of thirst and dry mouth were relieved with mouth care and
      sips of liquids far less than that needed to prevent dehydration. Food and fluid
      administration beyond the specific requests of patients may play a minimal role
      in providing comfort to terminally ill patients.

PMID- 7523743
TI  - [Reevaluation of current antimicrobials. Ceftazidime].

PMID- 7523744
TI  - [Refractory immune thrombocytopenic purpura accompanied with avascular necrosis
      of femoral head receiving the combination of high dose immunoglobulin therapy
      followed by platelet transfusion could successfully be managed to undergo
      surgery].
AB  - A 31 year-old male with refractory immune thrombocytopenic purpura (ITP) was
      accompanied with avascular necrosis of the femoral head on both sides, refractory
      to the following conventional therapies: high dose immunoglobulin (IgG) therapy,
      splenectomy, vinblastin slow infusion; maintaining a platelet count less than 20
      x 10(3)/microliters. He subsequently tried the combination of high dose IgG
      therapy with platelet transfusion from two single donors, which successfully
      increased the platelet count to more than 50 x 10(3)/microliters for as long as 9
      days. Compared to this method, platelet transfusion alone without IgG infusion
      failed to maintain an increase in the platelet count. These results suggest that
      high dose IgG may affect transfused-platelet removal in ITP. Management by the
      combination method enabled him to undergo surgery twice and he was able to walk
      with a stick six months later.

PMID- 7523742
TI  - Total parenteral nutrition decreases luminal mucous gel and increases
      permeability of small intestine.
AB  - The distribution of fluorescein isothiocyanate dextran 70,000 (FITC-dextran) and
      mucous gel across the lumen of small intestine was observed as an investigation
      into the role of mucous gel on permeability in total parenteral nutrition (TPN).
      Thirty-two rats were randomly divided into two groups fed with either TPN or oral
      rat food. On day 4 or 7, FITC-dextran (750 mg/kg body weight) was given through
      the gastroduodenal tube. After 1 hour, blood samples were taken by aortic
      puncture to analyze plasma FITC-dextran by fluorescence spectrometry. Samples of
      small intestine with luminal contents were frozen and sectioned in a cryostat for
      fluorescence microscopy; the same sections were placed in a 0.2% celloidin
      solution for 3 minutes to preserve mucous gel and stained by periodic acid-Schiff
      reaction for light microscopy. The plasma level of FITC-dextran after 1 hour of
      this marker injection showed a significant increase (p < .01) in the TPN group
      compared with the rat food group on days 4 and 7. Morphologic findings on days 4
      and 7 were similar in both the jejunum and ileum: The mucous gel filled the
      spaces between villi and FITC-dextran centered in the lumen in the rat food
      group, whereas the mucous gel decreased and FITC-dextran filled the spaces
      between villi in the TPN group. FITC-dextran and mucous gel showed complementary
      distributions in both groups. These data suggest that TPN decreases luminal
      mucous gel and increases permeability of small intestine in rats.

PMID- 7523745
TI  - [Cytokine and disease].
AB  - Cytokine is a generic term of biologically active molecules which are mainly
      produced by the immune-competent cells and regulate the immune response,
      inflammation and hematopoiesis. This includes interleukins (IL), colony
      stimulating factors (CSF), interferons (IFN), tumor necrosis factors (TNF) and so
      on. These cytokines are glycoproteins with a molecular weight of 20,000-40,000 kD
      and work at very low concentrations of pM order. ILs and CSFs transduce their
      signal via specific cell-membrane receptors which usually consist of at least two
      subunits and belong to a newly identified superfamily of cytokine receptors.
      Characterization of cytokine/receptor system has had a considerable impact on
      many clinical fields including pathophysiology of diseases and therapy. For
      example, IL-4 and IL-5 has been revealed to play essential roles in IgE
      production in allergic diseases and eosinophilia in a hypereosinophilic syndrome,
      respectively. Receptor abnormality has also been proven to cause diseases;
      patients for X-linked severe combined immunodeficiency (X-SCID) have a specific
      defect in the gamma chain of the IL-2 receptor which is critical for thymic
      maturation of T cells. EPO, G-CSF, M-CSF, IFN, and IL-2 are already commercially
      available for therapeutic use. IL-1, IL-3, IL-6, and TNF may also be useful for
      mycosis fungoides, aplastic anemia, thrombocytopenia, and malignant melanoma,
      respectively. On the other hand, it is possible to modulate the immune response
      by using the monoclonal antibody directed to the cytokine receptor.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7523746
TI  - [Interferon and diseases].
AB  - Interferon (IFN) is part of the body's natural defense system. IFN production is
      a cellular response to the foreign constituents of microbes, tumors and antigens.
      The three types (alpha, beta and gamma) of IFN proteins differ both structurally
      and antigenically and have molecular weights ranging from 16,000-25,000 daltons.
      The IFN proteins induce antiviral, antimicrobial, antitumor, and immunomodulatory
      actions. We reviewed the recent studies on the relation between IFN and diseases
      concerning; 1) the IFN-alpha and -gamma producing capacity in patients with
      cancers, liver cirrhosis, diabetes mellitus and rheumatoid arthritis, 2)
      endogenous IFN in sera and exudates or extracts of local lesions obtained from
      patients with immunological diseases such as SLE, sarcoidosis, rheumatoid
      arthritis, Behcet's disease, and psoriasis, 3) deletion of IFN-alpha and -beta
      genes in human lymphoblastoid cells lines and leukemia, and 4) the expression of
      IFN and other cytokine (interleukins and TNF) mRNA in normal organs under
      physiological conditions. Although IFNs may play an important role in cancers and
      immunological diseases, it is necessary to consider the interactions between IFNs
      and other cytokines as IFN is one of the factors involved in the cytokine network
      in vivo.

PMID- 7523747
TI  - [Criteria for the selection of hepatitis virus markers in liver diseases].

PMID- 7523748
TI  - [Basic and clinical studies on serum cytokeratin 19 fragment assay using Centocor
      CYFRA 21-1 kit in patients with lung cancer].
AB  - We evaluated the newly developed tumor marker assay kit, "Centocor CYFRA 21-1",
      an immunoradiometric assay (IRMA) kit for determining the serum cytokeratin 19
      fragment using the sera of healthy subjects, patients with benign lung diseases
      and patients with lung cancer. The assay procedure is simple and based on the one
      step IRMA system. There were no problems in reproducibility, dilution test and
      recovery test. The minimum detectable dose was 0.3 ng/ml. The antigen measured by
      this kit was immunologically cross-reactive with tissue polypeptide antigen (TPA)
      and CYFRA 21-1 concentration was closely correlated with TPA concentration in the
      patient's serum (r = 0.86, p < 0.01). The cut-off value of serum CYFRA 21-1 based
      on the assay results of this kit was calculated to be 1.6 ng/ml from the receiver
      operating characteristic curve. Three of 47 healthy subjects (6.4%) and 9 of 30
      patients with benign lung diseases (30.0%) showed a concentration over the cut
      off value. By contrast, serum CYFRA 21-1 concentration was elevated in 31 of 50
      patients with lung cancer (62.0%), 11 of 13 squamous cell carcinoma patients
      (84.6%), 8 of 12 small cell carcinoma patients (66.7%), 4 of 7 large cell
      carcinoma patients (57.1%) and 8 of 18 adenocarcinoma patients (44.4%). In
      addition, the positive rate of serum CYFRA 21-1 in patients with lung cancer
      gradually increased with staging of the disease: 50.0% in stage I, 50.0% in stage
      II, 61.9% in stage III, and 76.9% in stage IV. Thus, our results suggested that
      the Centocor CYFRA 21-1 kit is a useful assay system for serum cytokeratin 19
      fragment as a tumor marker in patients with lung cancer.

PMID- 7523750
TI  - FK506 inhibits renal glomerular thrombosis induced in rats by nephrotoxic serum
      and lipopolysaccharide.
AB  - We investigated the effect of the potent immunosuppressive agent, FK506, on
      experimental glomerular thrombosis in rats by combined injections of nephrotoxic
      serum (NTS) and lipopolysaccharide (LPS). Either FK506 or placebo was
      administered intramuscularly three hours prior to injection of NTS that was
      followed one hour later by LPS. Rats were killed five hours after the LPS
      injection. Compared with placebo, FK506 pretreatment significantly reduced
      thrombosis formation, in a dose-dependent manner. FK506 also reduced proteinuria
      and the rise of serum creatinine level. Early infiltration of polymorphonuclear
      leukocytes into the glomeruli after LPS injection was significantly suppressed in
      the FK506 group compared with the placebo group. We also measured serum tumor
      necrosis factor (TNF) activity by using an L929 fibroblast cytotoxicity assay.
      Peak serum TNF activity was observed one hour after LPS injection, and FK506
      significantly suppressed the elevation. Thrombosis was also developed in athymic
      nude rats, suggesting thrombosis formation is T cell independent. These data
      suggest that the FK506 has inhibitory effects on non-lymphocytes and possesses an
      anti-inflammatory effect in vivo.

PMID- 7523751
TI  - Coexisting NPY and NE synergistically regulate renal tubular Na+, K(+)-ATPase
      activity.
AB  - The sympathetic renal nerves are of central importance for the regulation of
      sodium balance. Sodium excretion decreases following renal nerve activation and
      increases following denervation. These effects have been attributed to
      norepinephrine (NE) acting on alpha-adrenergic receptors. In the present study,
      using isolated permeabilized rat renal proximal convoluted tubule (PCT) cells,
      neuropeptide Y (NPY) was shown to stimulate Na+, K(+)-ATPase activity. This 36
      amino acid peptide is a messenger molecule in the sympathetic nervous system
      which is co-stored with NE and dopamine-beta-hydroxylase (DBH), the NE
      synthesizing enzyme in the renal nerves. The effect is likely to be mediated via
      the NPY Y2 receptor, a pertussis toxin (PTX)-sensitive G-protein, and calcium. It
      is partially antagonized by alpha-adrenergic antagonists, and enhanced by the
      subthreshold doses of alpha-adrenergic agonists. Our results suggest an important
      role for this peptide in the regulation of the sodium balance in the kidney.

PMID- 7523749
TI  - [Mucinous adenocarcinoma of the prostate. A case report and analysis of the
      literature].
AB  - An 80-year-old man, who had been treated for colon cancer 25 years ago, presented
      with gross hematuria. Rectal examination revealed a soft nodule in the right
      lobe. The serum prostatic specific antigen (PSA) was elevated to 5.2 ng/ml, while
      prostatic acid phosphate (PAP) was normal. Transrectal ultrasound revealed a
      hypoechoic mass in peripheral zone of the prostate and dilated seminal vesicle. A
      needle biopsy of the prostate showed mucinous adenocarcinoma. Under the diagnosis
      of prostatic tumor with seminal vesicle involvement, radical prostatectomy was
      performed. Histological findings showed organ confined cancer, of which most was
      composed of extracellular mucin lakes. Immunohistochemical study revealed the
      tumor cells positive for PSA and PAP. Mucinous adenocarcinoma of the prostate has
      been known to be clinically different from non-mucinous adenocarcinoma, in that
      the former is insensitive to hormonal therapy, is rarely associated with elevated
      PAP and rarely metastasize to the bone. But our analysis of the literatures is
      Japan showed no significant difference clinically between mucinous and non
      mucinous prostatic adenocarcinoma. However mucinous adenocarcinoma with signet
      ring cell rarely responds to hormonal therapy, which should not be classified to
      true mucinous adenocarcinoma in the current criteria. True mucinous
      adenocarcinoma could be a variant of prostatic adenocarcinoma, which is
      peripheral origin and should be treated like non-mucinous adenocarcinoma.

PMID- 7523752
TI  - A prospective study of peritoneal transport in CAPD patients.
AB  - A prospective two year follow-up study of the functional characteristics of the
      peritoneal membrane was conducted in 61 CAPD patients. Peritoneal transport of
      solutes, calculated by mass transfer area coefficients for urea and creatinine,
      peritoneal clearances for proteins, percentage of absorption of glucose, as well
      as net ultrafiltration were measured every four months. After five months on CAPD
      a decrease was found for the transport of most solutes (P < 0.05, mean values,
      ml/min/1.73 m2): urea 18.1 to 16.2, creatinine 9.5 to 8.4, IgG 0.049 to 0.040 and
      alpha 2-macroglobulin 0.020 to 0.015, as well as for the absorption of glucose
      (57.9 to 53.2%, P < 0.05). Net ultrafiltration increased simultaneously from 44.6
      to 100.5 ml/4 hr/1.73 m2, P < 0.05. From five months to two years on CAPD a
      significant increase in the transport of all solutes except alpha 2-macroglobulin
      was found, as well as a decrease in net ultrafiltration. Peritoneal transport at
      the end of the study was not significantly different from the starting values.
      Our findings indicate an initial effect of CAPD itself on peritoneal transport,
      probably due to the recent start of the treatment. Baseline values were reached
      after five months on CAPD. Thereafter a gradual increase in peritoneal solute
      transport occurred during two years of treatment. This can be explained by an
      increase in the effective peritoneal surface area.

PMID- 7523753
TI  - Role of CD59 in experimental glomerulonephritis in rats.
AB  - CD59 is a molecule which is present on the host cell membranes and inhibits
      formation of membrane attack complex. A monoclonal antibody, 6D1, recognizes a
      rat analogue of human CD59. 6D1 inhibits function of rat CD59 and can enhance
      complement-mediated hemolysis in vitro. To assess the role of CD59 in complement
      mediated glomerular injury, 6D1 was tested in a model of experimental
      glomerulonephritis induced by a lectin and its antibodies. The left kidney of a
      rat was perfused either with 200 micrograms of Lens culinaris hemagglutinin (LCH)
      plus 1 mg of 6D1 (IgG1 fraction) (Group I and III) or with LCH only (Group II)
      through a cannula placed in the left renal artery. All the perfusate was
      discarded from a cannula in the renal vein. The holes in the artery and vein were
      repaired by microsurgery and the blood circulation was re-established. Rats were
      injected either with 0.125 ml of rabbit anti-LCH serum (Group I and II), or with
      normal rabbit serum (Group III) via tail vein one minute after the recirculation.
      Fifteen minutes after injection, significant C9 deposition in the glomeruli was
      observed only in Group I, whereas C3 deposition in Group I and II were
      comparable. At Day 4, total glomerular cells, proliferating cells, glomerular
      expression of intercellular adhesion molecule-1 and fibrin deposition in Group I
      were all significantly increased when compared with Group II. At Day 7, number of
      total glomerular cells and leukocytes in the glomeruli of Group I were
      significantly higher than in Group II. The glomeruli in Group III appeared normal
      throughout experiments. These data indicate that the functional inhibition of a
      rat analogue of human CD59 worsens complement-mediated glomerular injury in vivo.

PMID- 7523755
TI  - Detection of the antigenicity of the d-dimer of cross linked fibrin in the
      glomerulus by plasmin treatment.

PMID- 7523754
TI  - Endogenous nitric oxide synthesis determines sensitivity to the pressor effect of
      salt.
AB  - Endogenous nitric oxide plays an important role in modulation of renal
      hemodynamics and sodium handling, with increased nitric oxide production inducing
      renal vasodilation and natriuresis. In the normal rat, nitric oxide activity
      increases as an adaptive response to increased dietary salt intake, perhaps
      facilitating natriuresis and thus blood pressure homeostasis. We hypothesized
      that impaired nitric oxide synthetic ability would result in sensitivity to the
      pressor effects of high dietary salt intake. Four groups of normal Sprague-Dawley
      rats were observed for eight weeks: Control, 0.4% NaCl chow and tap water; Salt,
      4% NaCl chow and tap water; NAME, 0.4% NaCl chow and water containing the nitric
      oxide synthase inhibitor, L-nitro-arginine-methylester; Salt+NAME, 4% NaCl chow
      and water containing L-nitro-arginine-methylester. Compared to Controls, Salt
      rats demonstrated a significant increase in urinary excretion rate of the stable
      nitric oxide metabolites, NO2 and NO3, and had no increase in blood pressure.
      Furthermore, Salt rats had no functional or structural evidence of renal injury.
      In contrast, Salt+NAME rats demonstrated a significantly higher blood pressure
      than NAME rats, and urinary NO2 and NO3 excretion rate did not increase despite
      high salt intake. After eight weeks, Salt+NAME rats had significantly impaired
      renal function and proteinuria. We conclude that adaptive changes in endogenous
      NO production play a critical role in sodium and blood pressure homeostasis.
      Furthermore, impaired nitric oxide synthase activity may be a pathogenetic factor
      in the development of salt-sensitive hypertension.

PMID- 7523756
TI  - Evidence for delayed-type hypersensitivity mechanisms in glomerular crescent
      formation.
AB  - The role of CD4-positive T cells in glomerular crescent formation was examined in
      WKY rats. Glomerulonephritis (GN) was induced by a subnephritogenic intravenous
      dose of sheep anti-rat GBM antibody in rats previously sensitized to sheep
      globulin. This resulted in a severe proliferative and crescentic GN, with marked
      proteinuria [143 +/- 40 mg/24 hr (mean +/- SD), normal 1.6 +/- 0.7 mg/24 hr] and
      crescent formation involving 59 +/- 8% of glomeruli at day 10 (normal 0%).
      Humoral immunity to sheep globulin was evident systemically by high titers of
      circulating anti-sheep globulin and locally by linear deposition of rat
      immunoglobulin in glomeruli and cell mediated immunity by cutaneous delayed-type
      hypersensitivity (DTH) to intradermal injection of sheep globulin. Glomerular
      accumulation of CD5 positive T cells [2.45 +/- 0.21 cells per glomerular cross
      section (c/gcs), normal 0.18 +/- 0.10 c/gcs], CD4 positive T cells, (1.87 +/-
      0.46 c/gcs, normal 0.14 +/- 0.08 c/gcs), and macrophages (22.7 +/- 5.9 c/gcs,
      normal 0.05 +/- 0.05 c/gcs), together with the appearance of multinucleated giant
      cells (0.42 +/- 0.15 c/gcs, normal 0 c/gcs) suggested a DTH-like reaction in
      glomeruli. Sensitized rats given anti-GBM globulin were treated with monoclonal
      anti-CD5 or anti-CD4 antibodies in a protocol which prevented cutaneous DTH to
      sheep globulin without altering the humoral immune response. Both treatments
      significantly reduced glomerular accumulation of CD5 and CD4 positive T cells at
      day 10. Crescent formation was significantly reduced (CD5 treated, 13 +/- 4% of
      glomeruli affected; P < 0.001; CD4 treated 13 +/- 3% of glomeruli affected, P <
      0.001) compared to rats treated with an isotype-matched irrelevant monoclonal
      antibody. Glomerular macrophage accumulation, multinucleated giant cell formation
      and proteinuria were also significantly reduced by both treatments. These studies
      demonstrate a functional role for CD4 positive T cells as effector cells within
      glomeruli, separate from their role in humoral immunity, in the development of
      crescentic GN. The local participation of CD4 positive T cells, macrophages and
      multinucleated giant cells in crescent formation, and the attenuation of these
      features by functional T helper cell depletion suggest that local DTH-like
      mechanisms may contribute to glomerular crescent formation.

PMID- 7523757
TI  - A role for P selectin in complement-independent neutrophil-mediated glomerular
      injury.
AB  - Neutrophil recruitment and lung injury following complement activation have been
      demonstrated to be dependent on endothelial expression of P selectin. In anti
      glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) in
      mice, acute glomerular injury results from complement-independent neutrophil
      accumulation. The signals for neutrophil recruitment in this model are unknown.
      Expression of P selectin on glomerular endothelium was demonstrated within 30
      minutes of administration of anti-GBM antibody to C57/BL10 mice. This was
      associated with rapid accumulation of neutrophils in glomeruli which peaked at
      one hour (6.2 +/- 0.5 neutrophils per glomerular cross section [neut/gcs], normal
      0.34 +/- 0.06 neut/gcs, P < 0.01) and significant proteinuria after 16 hours (3.6
      +/- 0.5 mg/16 hr, control 0.62 +/- 0.13 mg/16 hr, P < 0.01). Complement depletion
      with cobra venom factor, which reduced serum C3 levels to less than 5% of normal,
      did not alter expression of P selectin, reduce glomerular neutrophil accumulation
      (6.7 +/- 0.8 neut/gcs) or proteinuria (3.7 +/- 0.5 mg/16 hr). Platelet depletion
      also failed to alter glomerular expression of P selectin, neutrophil accumulation
      or the development of proteinuria. Mice were treated with an affinity purified
      anti-human P selectin antibody, which cross reacted with mouse P selectin and
      blocked P selectin-dependent binding of thrombin-activated mouse platelets to
      HL60 cells and did not bind to mouse neutrophils. Treatment, one hour prior to
      the administration of anti-GBM antibody, markedly inhibited glomerular neutrophil
      accumulation (0.94 +/- 0.12 neut/gcs) and prevented proteinuria (1.0 +/- 0.2
      mg/16 hr), and did not alter binding of anti-GBM globulin in the kidney. These
      data strongly suggest that the rapid up-regulation of P selectin expression in
      glomeruli following binding of anti-GBM antibody is an essential signal for
      neutrophil recruitment in this complement independent model of glomerular injury.

PMID- 7523758
TI  - Localization of the complement regulatory proteins in the normal human kidney.
AB  - The kidney is an organ where complement-mediated tissue injuries take place by
      various stimuli. To assess how the kidney is protected from the autologous
      complement attack, comparative localization of decay accelerating factor (DAF),
      membrane cofactor protein (MCP) and 20 kDa homologous restriction factor (HRF20)
      was studied in the normal human kidney. Specific monoclonal antibodies to DAF,
      MCP and HRF20 were used for the study. Studies by immunofluorescence and
      immunoelectron microscopy showed that the distribution of each protein in the
      kidney was complementary to each other in most parts. MCP and HRF20 were clearly
      seen in the glomerular capillaries, while DAF was only faintly observed.
      Juxtaglomerular apparatus was abundant in DAF and MCP but not in HRF20. HRF20 was
      most strongly expressed in the peritubular capillaries where MCP was not
      detectable. Basolateral membranes of the proximal tubules and collecting ducts
      expressed MCP strongly, while there was no expression of DAF in the proximal
      tubules. Interestingly, both DAF and MCP, which inhibit complement activation at
      C3/C4 level, were not expressed in the apical portion of the tubular cells
      including proximal tubule brush border. In contrast, HRF20 was expressed on the
      apical part of the tubules. Medullary interstitium strongly expressed MCP but not
      DAF. Based on these observations, we conclude that each segment of the kidney is
      protected from the complement attack by the different combination of complement
      regulatory proteins. We speculate that the tubular cells might be fragile when
      complements are activated inside the tubular lumen, because there is no
      expression of complement regulatory proteins which inhibit C3 convertase.

PMID- 7523759
TI  - [Effectiveness of the analgesic, tramal, in the treatment of patients with
      oncologic diseases].
AB  - Tramal, the drug produced by the "Grunenthal" firm (FRG) was used in the
      treatment of 478 patients with malignant neoplasms. In 24.46% patients, the side
      effects were noted, which were characteristic of the majority of analgetics and
      didn't threaten the life. The authors recommend to use Tramal for cupping off the
      pain syndrome at the postoperative period, and in incurable patients as well.

PMID- 7523760
TI  - [Ocular involvement in Whipple disease].
AB  - PATIENTS AND METHODS We present a 57-year-old white man with progressive
      deterioration of vision, who had a prolonged history of weakness, migratory
      arthralgias and loss of weight. Bilateral panuveitis, with iritis, inflammatory
      vitreous opacities associated with small, round, grayish retinal lesions. The
      duodenum showed a swollen mucosa, which was flecked over with pinpoint grayish
      grains. A small-bowel biopsy disclosed PAS-positive granules in the macrophages
      of the lamina propria mucosa, pathognomonic of Whipple's disease. RESULTS After
      antibiotic treatment with trimethoprim and sulfamethoxazole there was no relapse
      of the panuveitis during the follow-up period of 18 months.

PMID- 7523761
TI  - A seroepidemiological study of hepatitis C virus (HCV) in an area with a high
      prevalence of chronic liver disease in the Kyushu district of Japan.
AB  - The incidence of hepatitis virus type C (HCV) in an area, Futase, of Iizuka city
      in Chikuho province in the northeastern part of Fukuoka prefecture in Kyushu,
      Japan, was estimated by screening sera for anti-HCV antibodies. Titers of anti
      human T-lymphotropic virus type I (HTLV-I) antibodies and hepatitis virus type B
      surface antigens (HBs) were also determined. The area of the present study is
      known to have a particularly high prevalence of chronic liver diseases, because
      coal mining was the key industry until a few decades ago. Also, in the old days
      it was rather isolated from the neighboring vicinities by surrounding mountains.
      The subjects of the present survey were 310 patients (117 males and 193 females)
      with various chronic diseases who visited Futase Social Insurance Hospital during
      a two year period from 1991 to 1992. Anti-HCV antibodies were detected in the
      sera of 55 patients, which is an overall positive rate of 18% (26% in male and
      14% in female patients). This is extremely high compared to an estimated
      nationwide average positive rate of 1.6%. Even in 270 patients with normal liver
      function, the incidence was as high as 10%. The incidences were particularly high
      in groups of patients aged 40 through 49, 50 through 59 and 60 through 69,
      ranging from 20 to 23%, while they were as low as 13 and 17% in those aged 70
      through 79 and 80 through 89 years, respectively. A high incidence, 57% was
      estimated for the patients with impaired liver function due to chronic liver
      diseases, especially in those concomitantly having diabetes mellitus (DM), 91%.
      The incidence of anti-HCV antibodies was the highest, 100%, in patients having
      both liver cirrhosis (LC) and DM. This was followed by those having chronic
      hepatitis (CH) and DM concomitantly and by those with LC alone, 86% each, and by
      those with CH alone 44%. Furthermore, the genotypes of the HCV in the sera of
      nine randomly selected carrier patients who had anti-HCV antibodies, even though
      they had diseases other than hepatic diseases and their liver functions were
      normal, were examined by the polymerase chain reaction method employing type
      specific primers for DNA amplification. As a result, all the HCV strains were
      type II. On the other hand, there were no apparent differences in the incidences
      of HTLV-I in the area of the present study and in neighboring provinces of the
      same prefecture, Fukuoka.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523762
TI  - P-selectin mediates the interaction of circulating leukocytes with platelets and
      microvascular endothelium in response to oxidized lipoprotein in vivo.
AB  - BACKGROUND: Oxidized low density lipoprotein (oxLDL) has been demonstrated to
      stimulate leukocyte/endothelium interaction, an early feature of atherogenesis.
      Using the skinfold chamber model for intravital microscopy in hamsters and mice,
      we have shown that oxLDL-induced leukocyte adhesion to microvascular endothelium
      shares many characteristics with leukocyte adhesion during inflammation and
      ischemia/reperfusion, including the involvement of beta 2 integrin adhesion
      molecules. In light of the two-step model of leukocyte adhesion, we have examined
      the contribution of P-selectin to oxLDL-induced leukocyte/endothelium
      interaction. P-selectin is an inducible adhesion molecule on platelets and
      endothelium, mediating the initial steps of leukocyte margination and rolling
      along the endothelial lining, as well as of aggregate formation between platelets
      and leukocytes. EXPERIMENTAL DESIGN: For our studies, we used the dorsal skinfold
      chamber model for intravital fluorescence microscopy on awake Syrian golden
      hamsters. Hamsters were treated 10 minutes before oxLDL-injection (oxidized by
      Cu2+, 4 mg/kg body weight, intravenously) with blocking antibodies to P-selectin
      (2 mg/kg body weight intravenously, N = 7). RESULTS: In seven control animals
      (pretreated with an irrelevant IgG antibody), oxLDL injection elicited leukocyte
      rolling and adhesion on both venular and arteriolar endothelium, and also the
      formation of aggregates tumbling down the microvessels and firmly adhering to the
      microvascular endothelium. The aggregates consisted of leukocytes and activated,
      dendritic platelets, as assessed by scanning electron microscopy of the buffy
      coat isolated by density gradient centrifugation of whole blood taken from
      hamsters 15 minutes after injection of oxLDL. Leukocyte adhesion to venular and
      arteriolar endothelium, as well as the formation of leukocyte/platelet aggregates
      were significantly reduced by pretreatment of the animals with anti-P-selectin
      antibodies. CONCLUSIONS: These data emphasize the similarities between leukocyte
      adhesion in response to oxLDL and in other pathophysiologic conditions,
      identifying P-selectin as a crucial player in the interaction between leukocytes
      and microvascular endothelium as well as in the formation of circulating
      leukocyte/platelet aggregates.

PMID- 7523763
TI  - Time course of recombinant protein secretion after liposome-mediated gene
      transfer in a rabbit arterial organ culture model.
AB  - BACKGROUND: Little information exists regarding the time course of gene
      expression after arterial transfection. Accordingly, we sought to determine the
      time course of gene expression after liposome-mediated arterial gene transfer
      (lipofectin) using an arterial organ culture model. EXPERIMENTAL DESIGN:
      Explanted segments of rabbit descending thoracic aorta were maintained in organ
      culture. Arterial gene transfer, facilitated by cationic liposomes (Lipofectin),
      was performed with the plasmid pXGH5 encoding the human growth hormone (hGH)
      under the control of mouse metallothionein-1 promoter. RESULTS: The time course
      of hGH production after transfection with the plasmid pXGH5 was evaluated.
      Significant levels (181.0 +/- 33.9 ng/24 hours/gm) of hGH were detected within 24
      hours post-transfection, reached a peak on day 7 (238.4 +/- 35.3 ng/24 hours/gm),
      and declined after day 10. At day 21, hGH could be observed in 50% of the
      arteries. Immunostaining with a monoclonal antibody for hGH revealed that only a
      small number of arterial cells (< 1%) were responsible for production of hGH.
      CONCLUSIONS: The organ culture model is a feasible and efficient means for
      investigating the kinetics of arterial gene transfer. Transfection of pXGH5
      results in significant levels of hGH for up to 3 weeks, despite anatomic evidence
      of only limited gene expression. These data thus support the notion that the
      magnitude and/or duration of gene expression may be disproportionately high,
      relative to anatomic assessment of transfection efficiency in the case of a
      transgene encoding for a secreted protein.

PMID- 7523765
TI  - Demonstration of heat-labile and heat-stable epitopes of Rickettsia japonica on
      ultrathin sections.
AB  - BACKGROUND: Spotted fever group rickettsiae including Rickettsia japonica have
      two major polypeptides and lipopolysaccharide (LPS)-like antigen on the surface.
      The major part of the antibodies to these polypeptides generated by immunization
      with live rickettsiae are reactive with heat-labile and conformation-dependent
      epitopes. EXPERIMENTAL DESIGN: To demonstrate and precisely localize the heat
      labile and heat-stable epitopes on the major surface polypeptides and LPS-like
      antigen of R. japonica, the immunocolloidal gold method was performed on
      ultrathin sections with polyclonal and monoclonal antibodies. The antigenicity
      and fine structure were preserved by using periodate-lysine-paraformaldehyde as
      fixative, followed by embedding with the resin Lowicryl K4M at a polymerization
      temperature of -35 degrees C. RESULTS: Heat-labile and heat-stable epitopes on
      the two major surface polypeptides together with LPS-like antigen of R. japonica
      were demonstrated at the same location. These antigens were rather broadly
      distributed on the cell wall apart from the slime layer of the organism. The
      number of gold particles corresponding to the LPS-like antigen was much larger
      than that corresponding to the polypeptide antigen. CONCLUSIONS: Heat-labile
      epitopes of rickettsiae could be preserved and demonstrated by using the
      procedure cited here. Moreover, the precise localization of the major surface
      polypeptides and LPS-like antigen could be achieved in the cell wall by using
      ultrathin sections of infected cells instead of whole rickettsial cells. The LPS
      like antigen was quantitatively predominant as judged by immunoelectron
      microscopy.

PMID- 7523766
TI  - Rearterialization of liver tumors after various dearterialization procedures.
AB  - Repeat dearterializations seem to be a means to prevent collateral formation,
      which is partly responsible for the failure of hepatic artery ligation (HAL) or
      permanent dearterialization when used to treat liver tumors. In this study
      restoration of tumor blood flow was evaluated after various procedures: HAL (n =
      12), permanent dearterialization (n = 18), repeated dearterializations for 2
      hr/day (n = 12), and sham dearterialization (n = 12). Tumor blood flow was
      measured 10 days after sham dearterialization, permanent dearterialization, and
      repeated dearterializations for 2 hr in order to further illustrate the effect of
      prolonged dearterialization on tumor rearterialization. Hepatic and tumor
      arterial blood flow was measured using the reference organ method (NEN, 141Ce
      microspheres with diameter 15 microns). Our results showed that during a
      transient dearterialization blood flow decreased to 1% (0.01 +/- 0.01 ml/min/g)
      of the flow in the controls (0.82 +/- 0.10 ml/min/g) (P < 0.01). After HAL tumor
      blood flow recovered to initial levels after 48 hr (0.73 +/- 0.17 ml/min/g). Even
      in rats subjected to a permanent dearterialization blood flow was reestablished
      at Day 6 (0.59 +/- 0.21 ml/min/g). In contrast, after repeat daily 2-hr
      dearteralizations blood flow remained significantly very low during the 6th
      transient dearterialization (0.11 +/- 0.03 ml/min/g) compared with both sham
      operation and HAL as well as permanent dearterialization (P < 0.01). During the
      10th daily dearterialization tumor blood flow was still significantly low
      compared with both controls (P < 0.001) and permanent dearterialization (P <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523764
TI  - Normal human pancreas cultures display functional ductal characteristics.
AB  - BACKGROUND: Normal cell cultures are invaluable in the analysis of cell
      differentiation and neoplastic transformation. EXPERIMENTAL DESIGN: We have
      developed methods to reproducibly culture normal pancreas epithelial cells. The
      characteristics of the cultures were analyzed using ultrastructural methods,
      antibodies, and cDNA probes detecting epithelial differentiation markers.
      RESULTS: Normal pancreas tissue (N = 56) was obtained from organ donors;
      isolation of highly enriched exocrine fraction consistently yielded epithelial
      cultures. In vitro proliferation assays revealed a lag growth phase of 2 days
      followed by a proliferative phase until 8. Epithelial cells formed a polarized
      monolayer displaying apical microvilli, tight junctions, and desmosomes. Zymogen
      granules were not observed. A panel of mouse monoclonal antibodies detecting
      differentiation antigens of epithelial cells was used to determine the phenotype
      of the cultures: all cells expressed cytokeratin polypeptides of simple
      epithelial (CK 7, CK 8, CK 18, and CK 19), whereas polypeptides typical of
      stratified epithelial (CK 5, CK 10, CK 13, and CK 16) were not detected. Cultured
      cells expressed the MUC1 apomucin as well as mucin-associated carbohydrate
      epitopes. Expression of the cystic fibrosis transmembrane regulator was
      demonstrated at the RNA level. Secretin induced a very high stimulation of cAMP
      levels. CONCLUSIONS: The ultrastructural characteristics, molecular markers, and
      hormone responsiveness of the cultures suggest a ductal cell phenotype. These
      cultures should be useful in the analysis of pancreas growth and differentiation.

PMID- 7523768
TI  - ACE inhibition and the vascular intima in hypertension.
AB  - Both the function and the morphology of the vascular intima are altered during
      hypertension. In spontaneously hypertensive rats, endothelium-dependent
      relaxation is decreased, and the subendothelium becomes infiltrated with monocyte
      macrophages. It is not known if these two features are secondary to high blood
      pressure and what their consequences are; however, both can be reversed by
      angiotensin-converting enzyme (ACE) inhibition. The present paper summarizes the
      effects of a chronic treatment with the ACE inhibitor cilazapril on endothelial
      function and subendothelial morphology in spontaneously hypertensive rats.

PMID- 7523767
TI  - The role of endothelium in cardiovascular homeostasis and diseases.
AB  - Key discoveries in the past decade have revealed that the vascular endothelium is
      an important regulatory organ that is involved in maintaining cardiovascular
      homeostasis in health and contributes significantly to the pathomechanism of
      several cardiovascular diseases. Occupying a strategically important location
      between circulating blood and tissues and having the ability to respond to
      changes in its physical, chemical, and humoral environment by the production of a
      host of biologically active substances, the normal endothelium modulates the tone
      of underlying vascular smooth muscle, maintains a nonadhesive luminal surface,
      and mediates hemostasis, cellular proliferation, and inflammatory and immune
      mechanisms in the vascular wall. Modulation of smooth-muscle tone is mediated by
      the synthesis release of endothelium-derived relaxing [PGI2, EDRF(NO), and EDHF]
      and contracting factors (arachidonic acid metabolites, endothelin-1, and
      angiotensin II). Anticoagulant, fibrinolytic, and antithrombotic properties
      contribute to the maintenance of the fluidity of blood. Injury or activation (by
      cytokines) of endothelial cells disrupts these normal regulatory mechanisms and
      results in morphologic and functional alterations (phenotypic changes) commonly
      defined as endothelial dysfunction. Clinically, the "syndrome" of endothelial
      cell dysfunction can be described as generalized or localized vasospasm,
      thrombosis, atherosclerosis, and restenosis. Although its importance is clearly
      established, no drugs used today were originally targeted for the treatment of
      endothelial dysfunction. Recent studies, however, showed that some existing
      therapies (e.g., angiotensin-converting enzyme inhibitors) may protect the
      endothelium. Novel diagnostic techniques and innovative therapeutic strategies,
      based on the already known molecular mechanisms of endothelial dysfunction, are
      briefly outlined. Further knowledge of the pathobiology of the impaired
      endothelium will contribute to unraveling some of the remaining mysteries of many
      cardiovascular diseases and will enable us to design novel therapies to prevent
      and treat them.

PMID- 7523769
TI  - Effect of cilazapril on the proliferative response after vascular damage.
AB  - Cilazapril, a novel long-acting inhibitor of angiotensin-converting enzyme,
      markedly suppressed the proliferative response and neointima formation after
      balloon catheter-induced injury of the carotid artery in a rat model of
      angioplasty. The reduction in neointima was dose-dependent, required sustained
      high levels of enzyme inhibition, and was significantly greater in animals
      treated starting 6 days prior to the procedure than in animals starting treatment
      the day of catheterization. In experiments with vascular smooth-muscle cells
      (SMC) in culture, the addition of angiotensin II reduces increased mRNA levels
      for several growth factors and extracellular matrix proteins. Here we report that
      Ang II selectively induces mRNA for thrombospondin I, but not for thrombospondin
      II. Under selected conditions SMC can be induced to proliferate after exposure to
      Ang II, in vitro and in vivo. Using neutralizing anti transforming growth factor
      beta (TGF-beta) antibodies we found that Ang II stimulation of proliferation was
      threefold greater when the anti-TGF-beta was added to the cultures. We suggest
      (a) that an important effect of Ang II during the proliferative response is the
      induction of thrombospondin I, which is required for matrix interactions during
      the formation of neointima, and (b) that, among the complex array of growth
      factors potentially active in vivo, TGF-beta may be an important negative
      regulatory factor that limits the proliferative response and prevents restenosis
      in most cases of angioplasty.

PMID- 7523770
TI  - Molecular mechanisms regulating the vascular endothelial cell motile response to
      injury.
AB  - Vascular endothelial cell (EC) wound healing was characterized on an EC
      synthesized extracellular matrix (ECM) previously treated with enzymes and
      antibodies specific for ECM components. Using a computer-assisted video
      microscope recording system capable of automatic EC recognition, we learned
      whether components of the EC-synthesized matrix influenced post-injury migration
      and wound healing in vitro. Localization of actin and its encoded mRNA using
      isoform-specific antibodies and labeled cDNA probes allowed for a direct
      correlation of living-cell behavior with cytoskeletal form and distribution.
      Results of these studies indicate that the computer-assisted EC tracking system
      allows for an automatic and reproducible analysis of EC behavior following injury
      in vitro. EC migrate fastest immediately following injury and then achieve a new,
      slower migration rate that is maintained until EC from one edge of 200- to 300
      microns-wide wound zone contact EC from the other wound face. Treatment of EC
      synthesized matrices with antibodies against fibronectin and laminin has no
      effect on EC migration following injury (-0.25 microns/min) or on cytoskeletal
      array. Similarly, digestion of these matrices with heparinase and hyaluronidase
      has no effect on wound healing rates. Slowly spreading EC cytoplasm, which
      borders the intact and antibody-treated EC matrices, is rich in actin but lacks
      myosin II. Two different preparations of collagenase (bacterial and mammalian)
      each potentiate EC wound healing in vitro. Bacterial collagenase treatment of the
      EC-synthesized matrices potentiates EC migration fivefold (1 micron/min) while
      treatment of EC-matrices with mammalian cell collagenase stimulates EC migration
      following injury some twofold (0.4 micron/min) over control values. Whereas EC on
      control matrices migrate in unison as a tissue-like sheet, EC on the collagenase
      treated EC matrices migrate as individuals. Concomitant with the increased rates
      of migration following injury on the collagenase-treated EC-matrices is a two- to
      fourfold increase in the steady-state levels of beta-actin mRNA. This increase in
      actin mRNA abundance is observable by its preferential localization (seen by in
      situ hybridization) in the lamellae bordering the wound edge in association with
      beta-actin, which is exclusively localized there. Because beta-actin and its
      encoded mRNA are positioned together in association with the plasma membrane in
      regions of moving cytoplasm, it seems likely that beta-actin filament assembly is
      required for motility following endothelial injury.

PMID- 7523771
TI  - Leukocyte adhesion molecules on the vascular endothelium: their role in the
      pathogenesis of cardiovascular disease and the mechanisms underlying their
      expression.
AB  - It is well known that granulocytes increase infarct size after reperfusion of the
      ischemic myocardium, and that monocytes promote atherogenesis. Those cells are
      also believed to play a contributory role in pathogenesis of coronary restenosis
      as response to arterial injury during balloon angioplasty. The adhesion of those
      leukocytes to the vascular endothelium is a prerequisite for their recruitment
      and accumulation in the lesion. Inflammatory mediators likely to occur under
      those conditions, e.g., histamine, thrombin, oxygen-derived free radicals (ODFR),
      interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and activated complement
      factors, induce in a distinct time course the (transient) expression of the
      leukocyte adhesion molecules P-selectin, E-selectin, intercellular adhesion
      molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 on the
      endothelium. Only VCAM-1 is specific for monocytes; the others mediate the
      binding and subsequent extravasation of both monocytes and granulocytes. The
      response to the relevant inflammatory mediators, except for extracellularly
      produced ODFR, is coupled via specific receptors on the surface of the
      endothelium to specific signal transduction pathways and, except for P-selectin
      (early response), is directly dependent on protein synthesis (intermediate and
      late response). Protein kinase-C-induced phosphorylation of transcription factors
      is often shown to be involved. Protein synthesis is preceded by increased
      transcription of mRNA that is regulated in part by the transcription factor NF
      kappa B. Indications have been obtained that intracellularly produced ODFR may be
      involved in the translocation of this transcription factor.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7523772
TI  - Patient, lesion, and procedural variables as risk factors for luminal re
      narrowing after successful coronary angioplasty: a quantitative analysis in 653
      patients with 778 lesions. Multicenter European Research Trial with Cilazapril
      after Angioplasty to prevent Transluminal Coronary Obstruction and Restenosis
      (MERCATOR) Study Group.
AB  - Follow-up angiography at 6 months was obtained in 94% of the 693 patients (778
      successfully dilated coronary lesions) enrolled in the Multicenter European
      Research trial with Cilazapril after Angioplasty to prevent Transluminal Coronary
      Obstruction and Restenosis (MERCATOR) trial--a double-blind, placebo-controlled
      trial--to study the effects of cilazapril 5 mg b.i.d. on restenosis [defined as
      the mean loss in minimal luminal diameter during follow-up, assessed by an
      interpolated edge detection technique (coronary angiography analysis system)] and
      long-term clinical outcome. No statistically significant difference could be
      detected between treatment and placebo groups with regard to clinical outcome or
      restenosis. The purpose of this ancillary study was to determine which, if any,
      patient, lesion, or procedural factors were predictive of restenosis. The
      identification of such factors could be helpful in the selection of lesions
      suitable for angioplasty and, if modifiable or controllable, potentially reduce
      restenosis. A stepwise multiple linear regression analysis was performed to
      identify independent predictors of restenosis. The following variables were
      retained in the model in order of significance: (a) relative gain (difference
      between the minimal luminal diameter pre- and post-percutaneous transluminal
      coronary angioplasty (PTCA), normalized for vessel size), (b) minimal luminal
      diameter post-PTCA, and (c) dilatation of another vessel than right coronary
      artery. The fit of the model was poor; where the predicted change in minimal
      luminal diameter was < 0.1 mm, 0.1-0.3 mm, > 0.3 mm, the corresponding percent
      correct classification was 30, 52, and 55%. The present study illustrates that
      the restenosis phenomenon cannot accurately be predicted by patient, lesion, and
      procedural variables.

PMID- 7523773
TI  - Different effects of Mg2+ on endothelin-1- and 5-hydroxytryptamine-elicited
      responses in goat cerebrovascular bed.
AB  - Mg2+ influences the response of cerebral arteries to several agonists, but until
      now its effects on endothelin-1 (ET-1) had not been studied. We recorded and
      compared the responses of goat cerebrovascular bed to ET-1 and 5
      hydroxytryptamine (5-HT) during various Mg2+ treatments. We performed experiments
      in vitro by recording isometric tension in isolated goat middle cerebral arteries
      and in vivo by recording cerebral blood flow (CBF) and other physiologic
      parameters in conscious goats. Cumulative addition of ET-1 (10(-11)-3 x 10(-8) M)
      and 5-HT (10(-9) -10(-5) M) contracted cerebral arteries concentration
      dependently in bath media containing 0 (Mg(2+)-free medium), 1 (control), and 10
      mM Mg2+, but the influence of Mg2+ was different: Mg2+ deprivation increased
      sensitivity (EC50) and Mg2+ overload reduced contractility (Emax) of cerebral
      arteries to 5-HT, whereas the ET-1 response did not change in these conditions.
      Cumulative addition of Mg2+ (10(-4)-3 x 10(-2) M) at the active tone induced by
      ET-1 (10(-9) M) and 5-HT (10(-5) M) elicited concentration-dependent relaxations
      of cerebral arteries, but the relaxant response was lower at the ET-1
      precontraction. Infusions of ET-1 (0.1 nmol/min) and 5-HT (10 micrograms/min)
      directly into the cerebroarterial supply of the unanesthetized goats elicited a
      sustained decrease in CBF and an increase in cerebral vascular resistance.
      Magnesium sulfate, administered as increasing doses (10-300 mg) in the same way
      increased CBF and decreased cerebral vascular resistance, although this effect
      was less on ET-1-induced than on 5-HT-induced cerebral vasoconstriction.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7523774
TI  - Calcitonin gene-related peptide stimulates a positive contractile response in rat
      ventricular cardiomyocytes.
AB  - Calcitonin gene-related peptide (CGRP) elicits marked positive inotropic and
      chronotropic actions in the atria of several mammals. The second-messenger
      substance cyclic AMP and activation of L-type calcium channels have been
      implicated in these actions, but CGRP failed consistently to stimulate a
      contractile response in ventricular tissue obtained from various mammals. We
      assessed the actions of CGRP using isolated ventricular cardiomyocytes obtained
      from adult rats. Maximum changes in cell length (dL) of isolated cardiomyocytes
      during electrically stimulated (0.5 Hz) contractions were determined with
      adenosine deaminase (2.5 U/ml). In these conditions, CGRP produced a potent
      concentration-dependent positive contractile response that became maximal 4 min
      after initial stimulation. CGRP increased amplitude of cellular contractions
      maximally at a 1-nM concentration to a value 21.4% greater than that obtained
      without peptide. The EC50 value for the response was 31 pM. At concentrations
      greater than 1 nM, amplitude of the cellular contractile response decreased
      rapidly. The CGRP2-selective agonist, [cys ACM2,7] CGRP, increased the amplitude
      of cellular contractions maximally at 500 nM to a value 19.8% greater than that
      obtained without peptide. EC50 for this response was 6 nM. Salmon calcitonin (<
      or = 100 nM) did not elicit a significant contractile response. The fragment,
      CGRP8-37, a selective antagonist at the CGRP1 receptor subtype, while devoid of
      agonist activity, was a potent competitive antagonist of the positive contractile
      action of CGRP (pA2 value = 7.95). CGRP, present at maximally effective
      concentration (1 nM), when combined with isoprenaline ISO 100 pM-1 microM,
      elicited a greater increase in contractile amplitude than that elicited by ISO
      100 pM-1 microM without CGRP. CGRP 1 nM combined with low concentrations of
      extracellular calcium ion < or = 4 mM produced a greater increase in contractile
      amplitude than that elicited by calcium ion < or = 4 mM without CGRP, but this
      additive effect was abolished in the presence of higher concentrations of
      extracellular calcium ion (> 4 mM). The cyclic AMP antagonist, Rp-cyclic AMPS (<
      or = 200 microM), did not inhibit the contractile response to CGRP 1 nM, but
      inhibited the contractile responses to ISO 100 nM and secretin 20 nM
      significantly and in a concentration-dependent manner. Diltiazem < or = 1 microM,
      a selective antagonist of L-type calcium channels, also failed to inhibit the
      contractile response to CGRP 1 nM but inhibited the contractile responses to ISO
      100 nM and secretin 20 nM significantly and in a concentration-dependent
      manner.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523775
TI  - In vivo study of the effect of exogenous estradiol on alpha-adrenoceptor
      responsiveness of human veins.
AB  - Based on previous experimental and epidemiologic findings, we hypothesized that
      17 beta-estradiol (E2) could decrease the alpha-adrenergic responsiveness in
      venous smooth muscle cells (VSMC), thereby decreasing venous tone and
      contributing to the pathogenesis of varicose veins. To test this hypothesis, the
      effect of an acute increase in E2 serum concentrations on venous alpha-adrenergic
      responsiveness to norepinephrine (NE) was studied in young healthy men. We
      conducted a double-blind, randomized, placebo-controlled cross-over study in 23
      male volunteers; 96 +/- 2 h after a single intramuscular (i.m.) injection of 10
      mg estradiol valerate or placebo, we quantified the pharmacologic effects of
      estradiol on alpha-adrenergic responsiveness of superficial hand veins by venous
      compliance technique (VCT) and on resting blood pressure (BP). After
      administration of estradiol, E2 serum levels increased 9.97 +/- 7.54-fold (mean
      +/- 1 SD, p < 0.001) to within the range of premenopausal preovulatory women. No
      significant difference was observed in mean dose of NE required for half-maximal
      venoconstriction (ED50, p = 0.224), however, or in the maximal effect of NE
      (Emax, p = 0.796) after administration of E2 as compared with placebo. A
      significant difference in diastolic BP (DBP) (p = 0.039) was observed after E2
      administration (64.6 +/- 7.7 mm Hg) as compared with placebo (68.3 +/- 7.6 mm
      Hg); BP (SBP) was not affected (p = 0.786). Our findings do not support the
      concept that E2 reduces alpha-adrenoceptor responsiveness of SMC in superficial
      veins.

PMID- 7523776
TI  - Perindopril and physiologic responses to exercise.
AB  - Cardiovascular drugs have varying effects on hemodynamic, metabolic, and hormonal
      responses to exercise. To evaluate the effects of the novel angiotensin
      converting enzyme (ACE) inhibitor, perindopril on these exercise-related
      responses, we studied 9 healthy volunteers in a double-blind, randomized, placebo
      controlled trial. After a week of perindopril 4 mg orally daily or placebo
      therapy, volunteers performed a treadmill effort test; the sequence was repeated
      after a 1-week washout period. Perindopril caused a significant reduction in mean
      resting systolic and diastolic blood pressure (SBP, DBP) without increasing
      resting heart rate (HR); 15-min post-exercise SBP was also significantly reduced.
      There were no significant differences between the perindopril and placebo effort
      tests with respect to metabolic indexes studied (serum K+, plasma glucose, plasma
      free fatty acids) or plasma hormonal concentrations measured (ACTH and cortisol,
      norepinephrine (NE) and epinephrine (EPI), glucagon and insulin, growth hormone
      and prolactin, renin activity). In the perindopril arm of the study, however,
      there were modest but significant increases in mean serum K+ before exercise to
      immediately after exercise (0.4 +/- 0.1 mM, p < 0.01) and mean plasma glucose
      from before exercise to 5 min (0.6 +/- 0.2 mM, p < 0.01) and 15 min (0.5 +/- 0.2
      mM, p < 0.05) after exercise. These data show that perindopril does not impair
      the hormonal changes associated with exercise in healthy subjects but induces a
      more consistent increase in blood K+ and glucose concentrations.

PMID- 7523777
TI  - Effects of the Ca2+ antagonist RO 40-5967 on endothelium-dependent responses of
      isolated arteries.
AB  - Experiments were designed to determine whether the Ca2+ channel inhibitor RO 40
      5967 [(1S,2S)-2-[2-[[3-(2-benzimidazolyl)propyl]methylamine]ethyl]-6- fluoro
      1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl methoxyacetate dihydrochloride] causes
      endothelium-dependent relaxations or inhibits endothelium-dependent contractions
      of isolated blood vessels. Rings of dog femoral, carotid, and basilar arteries
      and of rat aorta, with and without endothelium, were suspended in conventional
      organ chambers for measurement of isometric force. During contractions evoked by
      phenylephrine (full alpha 1-adrenergic agonist), St 587 (partial alpha 1
      adrenergic agonist) and endothelin-1 (ET), RO 40-5967 caused concentration
      dependent relaxations of rings of dog femoral arteries; the relaxations to RO 40
      5967 were greater in rings with endothelium than in those without endothelium.
      Nitro-L-arginine (NLA) and methylene blue (MB) inhibited the endothelium
      dependent component of the response to RO 40-5967 during contractions to
      phenylephrine (PE) St 587 and ET. The endothelium-dependent relaxations evoked by
      RO 40-5967 during contractions to PE were not affected by diltiazem in the
      femoral artery, suggesting that this effect of the compound may not be related to
      its calcium channel inhibitor properties. Under bioassay conditions, RO 40-5967
      stimulated release of relaxing factors from the endothelium of canine carotid
      arteries; the response of the detector tissues was inhibited by MB. In strips of
      canine femoral artery with endothelium, in which membrane potential of vascular
      smooth muscle cells (VSMC) was recorded with glass microelectrodes, RQ 40-5967
      did not cause endothelium-dependent hyperpolarizations.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7523778
TI  - Insulin sensitivity and atrial natriuretic factor during beta-receptor modulation
      with celiprolol in normal subjects.
AB  - beta-Receptor blockers may exert a spectrum of metabolic and humoral effects,
      which might differ depending on the specific adrenoreceptor characteristics of
      the individual agents. We investigated the influence of celiprolol, a beta 1
      blocker with beta 2-agonistic and, possibly, additional weak alpha-receptor
      antagonistic properties, on insulin sensitivity (SI), glucose homeostasis, and
      lipid profile in 20 young, healthy, normotensive individuals. SI, fasting plasma
      glucose and insulin, serum total triglycerides (TG), lipoprotein cholesterol (C)
      fractions, lipoprotein a [Lp(a)], and plasma atrial natriuretic factor (ANF)
      levels were determined before and after acute glucose loading under placebo
      conditions and after 3 weeks of celiprolol administration. The participants were
      instructed to follow a 3-day standard diet (2,500 kcal/day, 45% carbohydrates,
      40% fat, and 15% protein) and an overnight fast before measurements were
      recorded. As compared with control values, SI, fasting plasma glucose and
      insulin, the areas under the glucose and insulin curves, the k value of glucose
      disappearance after glucose load, and serum cholesterol fractions, TG, and Lp(a)
      were unchanged during celiprolol administration. However, celiprolol
      significantly reduced plasma ANF levels (p < 0.02). The latter increased in
      response to acute hyperglycemia/hyperinsulinemia with placebo (p < 0.05) but not
      with celiprolol. Although diastolic blood pressure (DBP) decreased slightly
      during the first and second week of celiprolol administration, BP and heart rate
      (HR) did not differ significantly after 3 weeks on celiprolol treatment as
      compared with placebo conditions. Our findings demonstrate that in healthy lean
      humans beta-receptor modulation with celiprolol is neutral with regard to SI and
      lipoprotein metabolism. Moreover, glucose loading stimulates whereas celiprolol
      decreases plasma ANF levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523779
TI  - Thrombolytic activity of YM866, a novel modified tissue-type plasminogen
      activator, in a photochemically induced platelet-rich thrombosis model.
AB  - We compared the thrombolytic activity of a novel modified tissue-type plasminogen
      activator (t-PA; del 92-173, 275Arg-->Glu), YM866, with that of t-PA in a
      platelet-rich thrombosis model. Thrombus was induced in guinea pig mesenteric
      artery by irradiation with filtered light in combination with intravenous (i.v.)
      administration of fluorescent dye. When occlusion by the thrombus extended to 99%
      of the luminal area of the vessel, test drug (YM866, t-PA, or saline) was
      administered by i.v. bolus injection under heparinization. Both YM866 and t-PA
      exhibited dose-dependent thrombolytic activity; however, the improvement in
      occlusion rate and the incidence of successful thrombolysis induced by YM866 were
      three times higher than those induced by t-PA. With YM866 1 mg/kg, alpha 2
      plasmin inhibitor levels decreased significantly to 58% of saline group values,
      but no change was noted in fibrinogen levels. YM866 antigen levels at this dose
      were seven times higher than those of t-PA. These results suggest that YM866 in
      single bolus injection is a thrombolytic agent superior to t-PA in platelet-rich
      thrombi without systemic fibrinolytic activation and that this efficacy is due to
      the prolonged half-life (t1/2) of the drug.

PMID- 7523780
TI  - Effect of halothane on in vivo and in vitro cardiotoxicity of an
      aminocardenolide.
AB  - Halothane opposes cardiotoxicity of neutral-sugar digitalis compounds in intact
      animals, presumably by depressing a sympathetic component of arrhythmogenesis.
      However, halothane also produces a dose-related reduction in arrhythmogenicity of
      ouabain in isolated canine Purkinje fibers, suggesting that the anesthetic may
      oppose direct mechanisms of cardiotoxicity as well. The present study examined in
      vivo and in vitro the effect of halothane on the arrhythmogenicity of ASI-222 (3
      beta-O[4-amino-4-6-dideoxy-beta-D-galactopyranosyl] digitoxigen in HCl), a highly
      polar aminocardenolide with no sympathetic component to cardiotoxicity. For in
      vivo studies, ASI-222 was infused at a rate of 1 microgram/kg/min until
      appearance of third-degree atrioventricular (AV) block or sustained ventricular
      arrhythmias in 5 conscious (control) and 6 halothane-anesthetized (1.4% end
      tidal) dogs. For in vitro studies, standard microelectrode techniques were used
      to measure action potentials (AP) in seven excised canine Purkinje fibers
      superfused with oxygenated Krebs-Henseleit buffer. AP were recorded during
      control superfusion, after induction of toxicity with 10(-7) M ASI-222, and
      during exposure to 0.5, 1.0, and 2.0% halothane. Purkinje fibers were paced at
      500-ms cycle lengths (CL) for 20 beats, and the amplitude of delayed
      afterdepolarizations (DAD) were recorded. Pacing at 250 ms CL was used to trigger
      ectopy. In vivo studies showed no difference in the cardiotoxic dose of ASI-222
      between control dogs and those anesthetized with 1.4% halothane. However, in 4 of
      6 anesthetized dogs, acutely increasing the inspired halothane concentration
      suppressed arrhythmias once end-tidal concentration were >2.2%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7523782
TI  - Differential effects of BDF 9148 and DPI 201-106 on action potential and
      contractility in rat and guinea pig myocardium.
AB  - The effects of BDF 9148 and its parent compound DPI 201-106 were compared in
      guinea pigs and rat cardiac tissue because these tissues possess long and short
      action potentials (AP), respectively, and have different excitation-contraction
      coupling mechanisms. Conventional electrophysiologic techniques were used to
      study drug effects on AP, sodium current, and force of contraction (Fc). In
      guinea pig and rat papillary muscle, BDF 9148 and DPI 201-106 increased Fc; BDF
      9148 was more potent than DPI 201-106. In guinea pig, but not in rat muscle, DPI
      201-106 significantly prolonged AP duration (APD) to a greater degree than did
      BDF 9148. In rat cardiac muscle, both agents were more potent but increased Fc to
      a lesser degree than in guinea pig cardiac muscle and led to Ca2+ overload, as
      evidenced by after-contractions and contracture. BDF 9148 failed to increase Fc
      at low frequencies in guinea pig but was effective at all frequencies in rat
      muscle. In isolated myocytes, substance effects on sodium current were similar in
      both species. In guinea pigs, but not in rats, DPI 201-106 prolongs APD to a
      greater degree than does BDF 9148. Both agents produce a greater positive
      inotropic effect in guinea pigs than in rats, which may be due to species
      differences in excitation-contraction coupling.

PMID- 7523781
TI  - Vasoconstrictors and renal protection induced by beta 1-selective adrenoceptor
      antagonist bisoprolol.
AB  - We investigated the role of the vasoconstrictors endothelin-1 (ET-1) and
      thromboxane in renal protection by the beta 1-selective adrenoceptor antagonist,
      bisoprolol, in Dahl salt-sensitive rats (Dahl S) and salt-resistant rats (Dahl
      R). Six-week bisoprolol treatment (20 mg/kg chow) reduced systolic blood pressure
      (SBP) by 14% in Dahl S rats fed a high-salt (4% NaCl) diet. This BP reduction was
      accompanied by a decrease in aortic wall thickness. ET-1 and thromboxane released
      from renal cortex was significantly decreased by 17 and 30% with bisoprolol,
      respectively. Other prostaglandin synthesis was unaffected. Renal function such
      as proteinuria, N-acetyl-beta-D-glucosaminidase (NAG) excretion, and glomerular
      filtration rate (GFR) was not influenced by bisoprolol. Morphologic investigation
      showed that bisoprolol significantly improved glomerular sclerosis by 29% and
      attenuated arterial damage by 71%, although tubular injury was not affected. The
      more severe the glomerulosclerotic lesions, the greater the generation of
      thromboxane and ET. The arterial lesions were positively correlated to
      thromboxane generation. These data indicate that long-term bisoprolol treatment
      reduces vasoconstrictive ET-1 and thromboxane generation and that these
      alterations may be partly responsible for the amelioration of glomerular and
      arterial injury in Dahl S rats.

PMID- 7523783
TI  - Activity of the L-arginine/nitric oxide pathway and endothelin-1 in experimental
      heart failure.
AB  - Neurohumoral changes influencing peripheral vascular resistance play a major role
      in congestive heart failure (CHF). We studied vascular function in 1-year-old
      cardiomyopathic syrian hamsters with pulmonary congestion and age-matched control
      hamsters. Aorta and mesenteric resistance arteries were suspended in organ
      chambers and myographs, respectively, for isometric tension recording. In aorta
      and mesenteric resistance arteries, contractile responses to norepinephrine (NE)
      were comparable in cardiomyopathic hamsters and controls. After inhibition of
      nitric oxide (NO) formation with nitro-L-arginine methylester (L-NAME),
      contractions to NE were enhanced in aorta of cardiomyopathic hamsters (p < 0.05);
      no effect was noted in controls or mesenteric resistance arteries. Low doses of
      endothelin-1 (ET-1 10(-10)-10(-9) M) caused stronger contractions in aorta of
      cardiomyopathic hamsters as compared with controls (p < 0.05). The sensitivity
      and maximal contraction to ET were more pronounced in mesenteric resistance
      arteries as compared with aorta in both cardiomyopathic and control hamsters (p <
      0.05-0.001). In both aorta and mesenteric resistance arteries, acetylcholine (ACh
      10(-9)-10(-5) M) induced concentration-dependent relaxation, which was prevented
      by L-NAME (p < 0.001). Maximal endothelium-dependent relaxation was more
      pronounced in aorta of cardiomyopathic hamsters (p < 0.05), but not different in
      mesenteric resistance arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523784
TI  - Protection of reperfused ischemic pig myocardium by nexopamil, a new combined
      Ca2+ and serotonin antagonist.
AB  - We investigated the ability of a newly developed calcium and serotonin (5-HT2)
      antagonist, nexopamil, to protect the heart from ischemia- and reperfusion
      induced myocardial injury. Anesthetized open-chest minipigs were subjected to 1 h
      left anterior descending coronary artery (LAD) occlusion and 3-h reperfusion.
      Thirty minutes before occlusion, one group of pigs (n = 7) received nexopamil
      (0.1 mg/kg intravenously, i.v.) and another group (n = 9) received vehicle.
      Nexopamil reduced infarct size (IS: tetrazolium stain) from 47 +/- 4% (vehicle)
      to 21 +/- 7% of the ischemic area (p < 0.05). In nexopamil-treated pigs, this was
      paralleled by reduced release of creatine kinase (CK) into coronary venous blood.
      In addition, nexopamil prevented reperfusion-associated myocardial contracture.
      Nexopamil decreased left ventricular peak pressure (LVPP) and pressure rate index
      (PRI) immediately before coronary occlusion by 11 and 18%, respectively.
      Coadministration of methoxamine (2 mg/kg, n = 6) with nexopamil increased LVPP
      and PRI to values of vehicle-treated pigs but did not prevent reduction in
      infarct size or CK activity in plasma. During reperfusion, neutrophil
      granulocytes showed increased formation of reactive oxygen metabolites
      (chemiluminescence) after stimulation with zymosan. Neutrophil counts in coronary
      venous blood were significantly reduced at 3 h reperfusion. Both changes were
      attenuated in nexopamil-treated pigs. Coronary occlusion resulted in increased
      platelet reactivity in coronary venous blood (collagen-induced aggregation) that
      was prevented by nexopamil. Nexopamil significantly increased the transcardiac
      (coronary venous-arterial) concentration gradients of 6-oxo-prostaglandin F1
      alpha (PGF1 alpha) without changing thromboxane (B2 (TBX2) concentrations,
      indicating a selective increase in cardiocoronary PGI2 formation. Nexopamil
      reduces myocardial injury in reperfused ischemic myocardium. Besides calcium
      channel blocking activity, inhibition of ischemia-induced neutrophil activation
      and enhanced endogenous PGI2 formation may be factors contributing to the
      beneficial effects of nexopamil.

PMID- 7523785
TI  - Influence of acute alpha 1-adrenergic antagonism on heart rate variability in
      patients with old myocardial infarction.
AB  - Decreased heart rate (HR) variation is a predictor of cardiac and arrhythmic
      death after myocardial infarction (MI). The present study examined the influence
      of alpha-adrenergic system on HR variation (HRV). A novel alpha 1-adrenergic
      antagonist, abanoquil (UK 52,046) was administered acutely to 27 patients with
      old MI in random placebo-controlled cross-over design. Abanoquil decreased mean
      sinus interval for 24 h from 884 +/- 119 (mean +/- SD) to 830 +/- 116 ms (p =
      0.0001). The total spectral (0.01-1.0 Hz) amplitude in HRV decreased from 44.6 +/
      14.8 to 40.6 +/- 14.8 ms (p = 0.018). Corresponding decreases were from 28.3 +/-
      10.6 to 25.3 +/- 10.8 ms (p = 0.011) in the low-frequency band (0.04-0.15 Hz) and
      from 13.8 +/- 6.6 to 12.1 +/- 6.1 ms (p = 0.055) in the high-frequency band (0.15
      0.40 Hz). Changes of similar magnitude were observed during active and sleep
      time. All changes in HRV were related by covariate analysis to the decrease in
      sinus interval and were not associated with an orthostatic decrease in blood
      pressure (BP) induced by abanoquil. The dominant effect of acute alpha 1
      adrenergic antagonism appears to be a decrease in parasympathetic activity,
      although it may also stabilize sympathetic control of the heart. Thus, the
      autonomic nervous modification caused by alpha-adrenoceptor antagonists might be
      disadvantageous in treatment of patients at high risk of fatal cardiac events.

PMID- 7523786
TI  - Chronic sympathectomy of canine cardiac ventricles affects Gs-adenylyl cyclase
      coupling and muscarinic receptor density.
AB  - The effect of chronic ventricular sympathectomy on sarcolemmal muscarinic
      receptor (MR) and beta-adrenoceptor densities and coupling of these receptors to
      adenylyl cyclase was examined. Microsomal membranes were isolated from right and
      left ventricles of control dogs (sham- and nonoperated) and dogs with ventricles
      sympathectomized 4 weeks earlier. Relative to control membranes, MR density was
      decreased in left but not right ventricular (LV, RV) membranes from
      sympathectomized hearts. Relative carbachol inhibition of adenylyl cyclase was
      similar in RV and LV membranes from both heart groups, however, Although beta
      adrenoceptor densities and ratio of beta 1- and beta 2-adrenoceptor subtypes did
      not change, basal adenylyl cyclase activity was 40% less in sympathectomized
      membranes as compared with control membranes. Furthermore, relative stimulation
      of adenylyl cyclase by isoproterenol was twofold greater in sympathectomized
      heart membranes. Because maximally stimulated adenylyl cyclase activity by NaF or
      MnCl2 was identical in sympathectomized and control membranes, the reduction in
      basal activity may not be related to a decrease in Gs and adenylyl cyclase. In
      support of this hypothesis, Gs alpha content as estimated from optimal cholera
      toxin-catalyzed ADP-ribosylation was similar in control and sympathectomized
      membranes. Therefore, an alteration in Gs interaction with adenylyl cyclase may
      account for the reduction in basal adenylyl cyclase activity and the increased
      relative responsiveness of adenylyl cyclase to isoproterenol in chronically
      sympathectomized ventricular membranes.

PMID- 7523787
TI  - Tubulin binding agent CI-980 has positive inotropic and local anesthetic actions.
AB  - Tubulin binding agents inhibit tubulin polymerization by actions at specific
      binding sites. CI-980 acts at the colchicine-binding site, which is distinct from
      the vinca-alkaloid binding site. We studied the actions of CI-980 in two models:
      neonatal rat myocytes in tissue culture and adult canine Purkinje fibers. In the
      first model, experiments on cell shortening and calcium signaling (using fluo3)
      showed that CI-980 increased the amplitude of both cell shortening and the Ca
      signal. The comparison drug, vinblastine, shared the effect on Ca signaling, but
      not that on cell shortening. In addition, high concentrations of CI-980 decreased
      the beating rate of spontaneously firing cell cultures. In canine Purkinje
      fibers, CI-980 decreased action potential amplitude (APA), Vmax, and conduction
      velocity and prolonged repolarization. It also decreased automaticity and
      suppressed delayed afterdepolarizations (DAD). These studies suggest that CI-980
      is a novel compound in that it exerts antiarrhythmic effects on the AP but is
      positively inotropic. Whether all these actions derive from a primary effect on
      tubulin or whether they reflect action on both tubulin and transsarcolemmal ion
      channels remains to be determined.

PMID- 7523789
TI  - Secretin and vasoactive intestinal peptide are potent stimulants of cellular
      contraction and accumulation of cyclic AMP in rat ventricular cardiomyocytes.
AB  - Although secretin and vasoactive intestinal peptide (VIP) stimulate production of
      the second-messenger substance cyclic AMP and exert a positive inotropic action
      on rat ventricle in vitro, a direct action of these peptides on cardiomyocytes
      has not been established. In contrast to hearts of other mammalian species, which
      possess VIP-preferring receptors, rat heart is unique in that the existence of a
      "relatively nonselective receptor" at which both secretin and VIP may bind has
      been proposed. We wished to define the receptor(s) for secretin and VIP present
      on rat ventricular cardiomyocytes using a homogeneous suspension of viable cells.
      With adenosine deaminase 5 U/ml and the phosphodiesterase (PDE) inhibitor
      isobutyl methylxanthine (IBMX) 1 mM, both secretin and VIP increased
      intracellular levels of cyclic AMP maximally and concentration dependently after
      5 min: EC50 values were 8 and 58 nM, respectively. At maximally effective
      concentrations, secretin 1 microM increased intracellular levels of cyclic AMP
      fourfold above basal levels, whereas a 1.6-fold increase was induced by VIP 10
      microM. Maximum changes in cell length (dL) of isolated cardiomyocytes during
      electrically stimulated (0.5 Hz) contractions were determined in the presence of
      adenosine deaminase 2.5 U/ml. Under these conditions, both secretin and VIP
      produced a concentration-dependent positive contractile response that became
      maximal 5 min after addition of the peptide. Secretin 50 nM increased the
      amplitude of cellular contractions maximally to a value 37% greater than that
      obtained without peptide. VIP 20 nM increased the amplitude of cellular
      contractions maximally to a value 19% greater than that obtained without peptide.
      The EC50 values were 470 and 700 pM for VIP and secretin, respectively. The
      selective antagonist at VIP-preferring receptors, 4-Cl DPhe-6 Leu-17 VIP 10
      microM did not antagonise the actions of VIP. In the presence of the selective
      antagonist at receptors for secretin, secretin 7-27 > or = 10 microM, the
      concentration dependence of the effect of secretin on accumulation of cellular
      cyclic AMP and contractile amplitude displayed a rightward parallel shift: the
      pA2 value for secretin 7-27 was 4.96. Secretin 7-27 also induced a rightward
      parallel shift of the concentration dependence of the actions of VIP. VIP 10
      microM was additive with low concentrations of secretin (< 10 nM) in stimulating
      production of cyclic AMP but antagonised this response at higher concentrations
      of secretin (> 10 nM). Similarly, VIP 2 and 20 nM enhanced the contractile
      response to low concentrations of secretin (< 1 nM), but antagonised the response
      at higher concentrations of secretin (> 1 nM).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523788
TI  - Effect of isradipine and nifedipine on diastolic function in patients with left
      ventricular dysfunction due to coronary artery disease: a randomized, double
      blind, nuclear, stethoscope study.
AB  - To elucidate the effect of isradipine and nifedipine on left ventricular (LV)
      systolic and diastolic function, each drug was given intravenously (i.v.) in
      equihypotensive doses to 10 patients accepted for coronary arteriography for
      stable angina pectoris. All 20 patients had LV ejection fraction (LVEF) of < 40%
      owing to previous myocardial infarction (MI). Systolic and diastolic function was
      assessed by standard hemodynamic parameters and pressure-volume relations
      measured by nuclear stethoscope. All measurements were taken at rest and during
      ischemia caused by right atrial pacing. Both systolic and diastolic parameters
      improved equally with isradipine and nifedipine. LVEF and cardiac output (CO)
      increased owing to peripheral vasodilatation. A decrease in P/Vmax, indicating a
      negative inotropic effect, was noted in patients at rest with both medications,
      but not during pacing-induced ischemia. With either medication, the time constant
      of relaxation and the end-diastolic elasticity constant decreased during pacing,
      indicating improvement in diastolic function, probably owing to relief of
      myocardial ischemia.

PMID- 7523790
TI  - New dihydropyridine calcium channel antagonist, pranidipine, attenuates
      hypertensive renal injury in Dahl salt-sensitive rats.
AB  - Interest in the cardiovascular protective effects of calcium channel antagonists
      has increased in the past decade. We investigated prevention of vascular wall
      remodeling by the long-acting calcium channel antagonist pranidipine in 12-week
      old Dahl salt-sensitive (SS) rats with high-salt-induced (4% NaCl) hypertension.
      Six-week pranidipine treatment (60 mg/kg chow) decreased systolic blood pressure
      (SBP) by 22% in SS rats. This BP reduction was associated with decreases in
      cardiac mass and weight of the aortic wall. Glomerular filtration rate (GFR) was
      increased by 33%, but this did not lead to a decrease in urinary protein or NAG
      excretion. Morphologic investigation demonstrated striking resolution of arterial
      injury (medial necrosis and/or hyperplasia, inflammatory cell infiltration, and
      thrombus formation) by 87% after pranidipine treatment. Glomerular sclerosis was
      also attenuated by 61%, whereas tubular injury was improved by only 28%. These
      morphologic changes were reflected in the findings that the capacity of kidney
      homogenate for generating lipid peroxides was significantly decreased and that
      collagen levels and pattern type became similar to those of normotensive salt
      resistant (SR) rats. Pranidipine also attenuated hypertensive vasculopathy in
      small arteries of the middle cerebral arteries. Thus, the calcium channel
      antagonist pranidipine can attenuate the vascular injury that occurs in salt
      induced hypertension, a promising property that implicates its clinical usage,
      particularly in essential hypertension with cardiovascular complications.

PMID- 7523794
TI  - Nursing practice cabinet poster sessions: getting the word out!

PMID- 7523793
TI  - Effects of heparinoids on the sclerotic reaction of rat thoracic aorta to injury:
      comparison between standard and low-molecular-weight heparins in vitro and in
      vivo.
AB  - To assess further the influence of heparinoids on arterial sclerosis, we compared
      the effects of standard heparin and of a low-molecular-weight (low-mol-wt)
      heparin (CY 216) in vitro on proliferation of cultured arterial smooth muscle
      cells (SMC) from rat aorta and in vivo on the sclerotic response of rat thoracic
      aorta to injury with a balloon catheter (SMC proliferation and deposition of
      elastin and collagen in the intima-media, using biochemical and histomorphologic
      techniques). Both heparinoids decreased replication of SMC in vitro in a similar
      dose-dependent manner. In vivo, heparin treatment [continuous intravenous (i.v.)
      administration, 60 IU/h/kg body weight (0.35 mg/h/kg)] inhibited all aspects of
      the aortic reaction for < or = 28 days after injury: synthesis of DNA (early peak
      of thymidine incorporation into DNA on D3.5); accumulation of DNA, collagen and
      elastin on D14 and D28; intimal thickening on D14. An equivalent treatment with
      CY 216 [60 antiactivated factor X (Xa) IU/h/kg (0.71 mg/h/kg)] exerted similar
      though less intense effects on the reaction of intima-media, as assessed
      biochemically, but reduced formation of neointima in a proportion nearly
      identical to that of heparin. In some respects, which appear to be related mainly
      to the fibrotic reaction of aortic media to injury, heparin tended to be a
      slightly more potent antisclerotic agent than CY 216 although, owing to
      pharmacokinetic differences, CY 216 had stronger plasma anti-Xa activity than
      heparin.

PMID- 7523792
TI  - Endothelin-1-selective binding sites are downregulated by transforming growth
      factor-beta and upregulated by basic fibroblast growth factor in a vascular
      smooth muscle-derived cell line.
AB  - Endothelins (ETs) elicit in vivo and in vitro a potent vasoconstrictor activity
      after binding to high-affinity receptors on vascular smooth muscle cells (VSMC).
      A617 cells, a VSM-derived cell line, were used as an in vitro model system to
      study selected growth factors and cytokines involved in proliferative and/or
      inflammatory diseases of the vessel wall as possible regulators of the high
      affinity binding capacity of ET-1 to the cells. Radioligand studies characterized
      the binding of ET-1 to the isopeptide selective ETA receptor subtype on A617
      cells as a time- and temperature-dependent saturable process (Kd = 0.13 +/- 0.04
      nM, Bmax = 49 +/- 7 fmol/10(6) cells). Pretreatment of A617 cells with basic
      fibroblast growth factor (bFGF), a mitogenic agent for vascular cells, resulted
      in a time- and dose-dependent increase in ET-1 binding capacity, whereas
      preexposure to transforming growth factor-beta (TGF-beta) induced a reduction of
      the Bmax for ET-1. Platelet-derived growth factor (PDGF), interleukin-6 (IL-6),
      tumor necrosis factor-alpha, and fetal bovine serum (FBS) pretreatments did not
      affect consequent ET-1 binding to A617 cells.

PMID- 7523795
TI  - Cytokine and growth factor gene expression by bone marrow stroma of mice with
      damaged hematopoiesis and during regeneration.
AB  - A study of gene expression of GM-CSF, IL-3, c-kit ligand, and IL-1 by bone marrow
      stromal cells of mice who were treated with an LD50 cytosine arabinoside (Ara-C)
      dose was carried out. It was shown previously that this dose causes extensive
      hematopoietic damage which is followed by regeneration in surviving mice. Using
      PCR, we demonstrated GM-CSF and IL-1 expression by adherent cells taken from
      marrow fibroblast layers following Ara-C-induced hematopoietic damage and during
      marrow regeneration, while expression in control layers was not detected. The IL
      3 gene was not expressed either by layers of Ara-C-treated mice or by controls,
      probably due to the absence of T-lymphocytes in 2-4 week old cultures. The c-kit
      ligand gene was expressed by layers during marrow regeneration and by control
      layers, but was absent during the stage of hematopoietic damage. In parallel, in
      vitro cytokine production was evaluated. While IL-3 and GM-CSF were not present
      in the conditioned medium of marrow fibroblast layers either from Ara-C-treated
      mice or controls, IL-1 was found in low concentrations in cultures from Ara-C
      treated animals. We conclude that GM-CSF, c-kit ligand and IL-1 have important
      roles in sustaining marrow regeneration following extensive damage. The role of
      IL-3 in marrow regeneration cannot be assessed in fibroblast layers of 2-4 week
      incubation where T-lymphocytes are generally absent.

PMID- 7523796
TI  - Polyamine transport in human promyelocytic leukemia cells and polymorphonuclear
      leukocytes.
AB  - We examined the kinetics of polyamine uptake by human myeloid cells at different
      stages of maturity. The Km values of putrescine, spermidine and spermine
      transport by HL-60 cells were 52, 7.9 and 8.1 microM, respectively. These values
      decreased to 5.1, 1.7 and 0.77 microM, respectively, in HL-60 cells induced to
      mature past the promyelocyte stage by DMSO. In human PMNs, the respective Km
      values were 501, 479 and 381 microM. Transport by HL-60 cells was enhanced when
      intracellular polyamine levels were reduced with difluoromethylornithine. Thus,
      HL-60 cell maturation is accompanied by an increase in the affinity of their
      polyamine transport system. This system is much more efficient than that found in
      end-stage PMNs, suggesting that it plays a more important role in supporting the
      metabolic requirements of HL-60 cells. Alternatively, the low affinity of the PMN
      polyamine transport system could represent an adaptation to the high polyamine
      concentrations found at infection sites.

PMID- 7523797
TI  - The immunological profile of B-cell disorders and proposal of a scoring system
      for the diagnosis of CLL.
AB  - We have investigated the role of immunophenotyping in distinguishing between
      leukemic B-cell lymphoproliferative disorders. Circulating cells from 666 cases
      were analyzed with a panel of markers by flow cytometry. The diseases included:
      chronic lymphocytic leukemia (CLL), 400; prolymphocytic leukemia, 22; hairy cell
      leukemia (HCL), 40; HCL variant, 15; splenic lymphoma with villous lymphocytes,
      100; follicular lymphoma, 26; lymphoplasmacytic lymphoma, 25; mantle-cell
      lymphoma, 20; and large cell lymphoma, 18. On the basis of the most common marker
      profile in CLL, CD5+, CD23+, FMC7- and weak expression (+/-) of surface
      immunoglobulin (SmIg) and CD22, we devised a scoring system that gives for each
      of these five markers a value of 1 or 0 according to whether it is typical or
      atypical for CLL. Scores range from 5 (typical of CLL) to 0 (atypical for CLL).
      Application of the scoring system to all the cases showed that 87% of CLL scored
      5 and 4 and only 0.4% scored 0 or 1, whereas 89% of other B-cell leukemias and
      72% of lymphomas scored 0 or 1; only one case (0.3%) scored 4 and none scored 5
      (p < 0.0001). There were no differences between CLL with high and low scores but
      higher scores were found in cases with more typical morphology (p < 0.0015).
      Considering each individual marker, there was no single one that distinguished
      CLL from other diseases, although the most reliable were SmIg intensity and FMC7.
      The proposed score will facilitate the diagnosis of B-lymphoproliferative
      disorders and improve their classification.

PMID- 7523791
TI  - Cardiac norepinephrine, beta-adrenoceptors, and Gi alpha-proteins in
      prehypertensive and hypertensive spontaneously hypertensive rats.
AB  - In spontaneously hypertensive rats (SHR), cardiac adenylate cyclase is
      desensitized owing to down-regulation of myocardial beta-adrenoceptors and an
      increase in Gi alpha. We wished to determine whether these biochemical
      alterations in the beta-adrenoceptor-adenylate cyclase system precede development
      of hypertensive cardiac hypertrophy or whether this increase occurs only in later
      stages of the syndrome and represents a secondary phenomenon. Myocardial samples
      from 5- and 13-week-old SHR and age-matched Wistar Kyoto rats (WKY) as controls
      were studied. Cardiac beta-adrenoceptors were studied with [125I]cyanopindolol
      ([125I]ICYP] as radiolabeled ligand. beta-Adrenoceptor subtypes were determined
      with the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551,
      respectively. Gi alpha proteins were measured with the pertussis toxin-catalysed
      [32P]ADP ribosylation. Myocardial norepinephrine (NE) content was investigated
      with high pressure liquid chromatography. In myocardial membranes of 13-week-old
      SHR, the number of total beta-adrenoceptors as well as beta 1- and beta 2
      adrenoceptors was reduced. No difference was observed between SHR and WKY, at age
      5 weeks. The nonionic detergent Lubrol PX at 0.5% (vol/vol) increased the amount
      of detectable Gi alpha by a factor of 14. Under these optimal conditions, Gi
      alpha was increased by 30% in 13-week-old SHR, but not 5-week-old SHR as compared
      with WKY. Myocardial NE content was increased by 25-35% in both 5- and 13-week
      old SHR as compared with WKY. The results showed that nonspecific beta
      adrenoceptor downregulation and an increase in Gi alpha occurs in hypertensive
      cardiac hypertrophy of SHR. In the prehypertensive stage, these changes were not
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7523798
TI  - Mechanisms of p53 alteration in acute leukemias.
AB  - Disruption of normal p53 expression is the most frequent genetic change occurring
      in various human solid tumors; it is mostly due to sequence alterations of the
      p53 coding region by missense mutations or to loss of an entire, functional
      allele of this gene. In the present study, possible mechanisms resulting in a
      disruption of regulated expression of wild-type p53 were examined in acute
      leukemias of either lymphoid (ALL) or myeloid (AML) phenotype. p53 transcript
      accumulation, nucleotide sequence and gene structure were analyzed in primary
      leukemic cells from 50 patients. p53-specific transcripts were detected in 26/26
      cases of ALL and 16/23 cases of AML using reverse transcriptase (RT)-PCR.
      Sequencing of transcripts did not reveal any point mutations or deletions.
      Heterozygosity at a polymorphic Bg/II site within intron 1 was found in 4/28
      leukemic samples, and loss of one allele was noted in one of these. In addition,
      a novel, leukemia-associated structural abnormality located within the 5'
      flanking region of the p53 gene and associated with the loss of heterozygosity
      was observed in cells from this patient with ALL. The MDM2 gene which inactivates
      p53 by binding to it was neither amplified nor rearranged in 28 leukemias
      studied. Thus, disruption of regulated p53 expression resulting in lack of
      detectable p53 mRNA even by RT-PCR occurs in about 30% of cases of AML; however,
      p53 alterations typical for human solid tumors are an infrequent event in most
      types of human acute leukemias.

PMID- 7523799
TI  - Migration of acute lymphoblastic leukemia cells into human bone marrow stroma.
AB  - Most cases of acute lymphoblastic leukemia (ALL) arise from malignant
      transformation of B-cell precursors in the bone marrow. Recent studies have shown
      that normal and leukemic B-cell precursors bind to bone marrow stromal cells
      through the beta-1 integrins VLA-4 and VLA-5, thereby exposing early lymphoid
      cells to regulatory cytokines. It has been recently reported that the pre-B cell
      line NALM-6 is capable of migrating under layers of murine stromal cells in vitro
      (Miyake et al. J Cell Biol 1992;119:653-662). We have further analyzed leukemic
      cell motility using human bone marrow fibroblasts (BMF) as a stromal layer. The
      precursor-B ALL cell line NALM-6 rapidly adhered to BMF, and underwent migration
      or tunneling into BMF layers within 5 h, as demonstrated by light and electron
      microscopy, and confirmed by a chromium-labeling assay. Migration was also
      observed with the precursor-B ALL lines Reh and KM-3, with a T leukemia line RPMI
      8402, the monocytic line U937, and the mature B line Daudi. In contrast, mature B
      (Raji), myeloid (K562, HL-60), and T lines (CCRF-CEM, MOLT-4) did not migrate.
      When cases of leukemia were analyzed, BMF migration was largely confined to
      precursor-B ALL, occurring in eight of 13 cases tested. Of other types of
      leukemia, migration was observed in one of four cases of T-ALL, but no evidence
      was seen in six acute myeloid leukemias and two patients with chronic lymphocytic
      leukemia. Only minimal migration into BMF was observed with purified sorted CD10+
      CD19+ early B cells from normal adult marrow, while normal mature B lymphocytes
      from peripheral blood did not migrate. ALL migration was inhibited by monoclonal
      antibodies to the beta sub-unit of the VLA integrin family, and by a combination
      of antibodies to VLA-4 and VLA-5. Partial inhibition was also observed when
      leukemic cells were incubated with antibodies to VLA-4, VLA-5, or VLA-6 alone. In
      contrast, treatment of stromal cells with antibodies to vascular cell adhesion
      molecule or fibronectin (ligands of VLA-4 and VLA-5) did not prevent leukemic
      cell migration. These results indicate that ALL cells are highly motile and
      capable of rapid migration within marrow stroma, an effect largely mediated by
      VLA-4 and VLA-5. In the case of precursor-B ALL, this process may reflect a
      homing mechanism to areas of selective growth advantage within the bone marrow
      microenvironment.

PMID- 7523800
TI  - Modulation of IL-8, IL-1 beta, and G-CSF secretion by all-trans retinoic acid in
      acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid
      leukemias (AML) characterized by the presence of the t(15;17) translocation and
      the resulting PML/RAR alpha fusion proteins. To date APL is the only AML which is
      sufficiently sensitive to all-trans retinoic acid (ATRA) differentiating effect.
      We have recently reported that APL express and secrete hematopoietic growth
      factors (HGF) such as IL-1 beta, TNF alpha, and IL-6. In vivo ATRA alone allows
      achievement of complete remission in APL patients. One of ATRA therapy's
      drawbacks is the increase of peripheral blast cells often associated with the
      ATRA leukocyte activation syndrome. To determine if this specific side-effect was
      linked to an increase of HGF release by APL cells, we studied the modulation of
      cytokine production by APL cells, we studied the modulation of cytokine
      production by APL samples (n = 12) before and after incubation with ATRA. ATRA
      failed to modulate TNF alpha, IL-6 or GM-CSF secretion levels; however, IL-8
      levels decreased in 11 cases, and in four cases up-regulation of IL-1 beta and G
      CSF protein expression was observed. These modulations were found to be linked to
      ATRA sensitivity as ATRA failed to modulate cytokine production in non-APL cells
      (n = 8). Interestingly, the increase of IL-1 beta and G-CSF production in the
      presence of ATRA was highly correlated to an increase in APL cell count in vitro
      and in vivo hyperleukocytosis, resulting in fatal outcome. IL-1 beta, TNF alpha,
      IL-6, and IL-8 are known to be implicated in leukocyte activation. The results of
      this study suggest that ATRA-induced hyperleukocytosis and ATRA leukocyte
      activation syndrome in APL may be inherent to the secretion of specific
      hematopoietic growth factors by the APL cells.

PMID- 7523803
TI  - [Endotoxin may also inhibit the constitutive synthetase enzyme of nitric oxide].

PMID- 7523801
TI  - Molecular diversity in AML1/ETO fusion transcripts in patients with t(8;21)
      positive acute myeloid leukaemia.
AB  - Patients with acute myeloid leukaemia with maturation (AML-M2) that carried the
      t(8;21) were tested for the presence of chimeric AML1/ETO mRNA. After RT-PCR, an
      expected band of 208 bp was observed on gel, as well as some slower migrating
      bands. The base composition of one of the additional products was determined and
      was found to contain a new 68-bp ETO sequence present at the fusion of AML1 and
      ETO genes. The derived protein sequence results in a truncated AML1 gene still
      containing the putative DNA binding domain. Molecular diversity in the AML1-ETO
      transcripts will have consequences for the detection of minimal residual disease
      and antisense studies.

PMID- 7523804
TI  - Colonocytes in Barrett's metaplasia?

PMID- 7523802
TI  - Vancouver hybrid: preliminary experience in the treatment of Hodgkin's disease in
      childhood and adolescence.
AB  - OBJECTIVE: To describe our preliminary experience with 19 young patients with
      newly diagnosed Hodgkin's disease who received the Vancouver hybrid
      chemotherapeutic regimen. DESIGN: We summarized the characteristics of our 19
      study patients, the treatment administered (between June 1988 and June 1992), and
      the outcome. RESULTS: The Vancouver hybrid, which consists of mechlorethamine,
      vincristine sulfate (Oncovin), procarbazine hydrochloride, prednisone,
      doxorubicin hydrochloride (Adriamycin), bleomycin, and vinblastine sulfate
      (MOPP/ABV), was based on the hypothesis of preventing drug resistance by early
      introduction and alternation of all active agents and was aimed at decreasing the
      severity and frequency of treatment-related complications. Of our 19 patients
      with Hodgkin's disease (age range, 6 to 20 years) treated with this regimen, 2
      had clinical stage I disease, 10 had stage II, 6 had stage III, and 1 had stage
      IV. Only two patients had systemic symptoms, and nodular sclerosis was the most
      common histologic feature. Patients were given four to eight cycles of
      chemotherapy, depending on the clinical stage of disease. In addition, 10
      patients received irradiation, including 6 of 9 patients with bulky disease. In
      all patients, complete remission was achieved. After a median follow-up of 3.3
      years, only two patients had had a relapse; both underwent autologous bone marrow
      transplantation and were alive and well with no evidence of disease at last
      follow-up. The treatment was well tolerated, and delivery of treatment was
      excellent. The only severe toxicity was myelosuppression; 8 patients experienced
      a total of 15 episodes of fever and neutropenia that necessitated hospitalization
      and antibiotic therapy, but no systemic infections were confirmed during 104
      cycles of therapy. CONCLUSION: The MOPP/ABV hybrid is an effective and well
      tolerated therapy in most young patients with Hodgkin's disease. Long-term
      monitoring is needed to evaluate late effects.

PMID- 7523805
TI  - Tacrolimus (FK506) versus cyclosporin in prevention of liver allograft rejection.

PMID- 7523806
TI  - Tacrolimus (FK506) versus cyclosporin in prevention of liver allograft rejection.

PMID- 7523807
TI  - Tacrolimus (FK506) versus cyclosporin in prevention of liver allograft rejection.

PMID- 7523809
TI  - Risperidone in HIV-related manic psychosis.

PMID- 7523810
TI  - Staining of amyloid precursor protein to study axonal damage in mild head injury.
AB  - The most common definition of cerebral concussion is that of a transient loss of
      neurological function without macroscopic or microscopic abnormality in the
      brain. However, some patients have persistent symptoms and subtle
      neuropsychological deficits, particularly affecting memory. We have studied five
      patients aged 59-89 years who sustained mild concussive head injury and died of
      other causes (2-99 days post-injury). Immunostaining with an antibody to amyloid
      precursor protein, a marker of fast axonal transport, showed multifocal axonal
      injury in all five. All had axonal damage in the fornices, which are important in
      memory function.

PMID- 7523811
TI  - Keratin genes and epidermolytic hyperkeratosis.

PMID- 7523808
TI  - Raised nitrate concentrations in chronic heart disease.

PMID- 7523812
TI  - Treatment of frostbite with iloprost.

PMID- 7523813
TI  - Colorectal cancer.

PMID- 7523814
TI  - Endothelial cell harbingers of adult respiratory distress syndrome in acute
      pancreatitis.

PMID- 7523815
TI  - Risperidone-induced neuroleptic malignant syndrome.

PMID- 7523816
TI  - Grey platelet syndrome.

PMID- 7523817
TI  - Multilineage response to G-CSF in paediatric aplastic anaemia.

PMID- 7523818
TI  - Localization of IL-1 beta mRNA and cell adhesion molecules in the maxillary sinus
      mucosa of patients with chronic sinusitis.
AB  - Interleukin-1 beta (IL-1 beta) is a predominant cytokine in retained paranasal
      sinus fluid of chronic sinusitis where infiltration by polymorphonuclear
      neutrophils (PMNs) of nasal and paranasal mucosa is characteristic. The authors
      investigated the localization of IL-1 beta messenger RNA (mRNA) in the maxillary
      sinus mucosa of patients with chronic sinusitis, using digoxigenin-labeled
      oligonucleotide probes. IL-1 beta mRNA was detected in some extravascular PMNs
      and small numbers of mononuclear leukocytes but was not detected in other tissue
      cells or intravascular leukocytes. The expression and distribution of the cell
      adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and endothelial
      leukocyte adhesion molecule-1 (ELAM-1), were also studied in cultured human
      mucosal microvascular endothelial cells and in the maxillary sinus mucosa in
      chronic sinusitis by immunohistochemistry using monoclonal antibodies against
      these cell adhesion molecules. Only ICAM-1 was expressed on cultured human
      mucosal microvascular endothelial cells without IL-1 beta stimulation. With IL-1
      beta activation of these cells, ELAM-1 was expressed strongly and the expression
      of ICAM-1 was enhanced. In the maxillary sinus mucosa, ICAM-1 was strongly and
      universally expressed on endothelial cells of all small vessels, whereas ELAM-1
      was expressed only in the subepithelial region. These findings suggest that IL-1
      beta, one of mediators in chronic sinusitis, is produced by PMNs, induces the
      expression of ICAM-1 and ELAM-1 on endothelial cells, and, thereby, stimulates
      PMN infiltration in chronic sinusitis.

PMID- 7523819
TI  - [Effect of thyrotropin releasing hormone and histidyl-proline diketopiperazine on
      enzyme section of isolated pancreatic acinar cells of the rat].
AB  - The effect of thyrotropin-releasing hormone (TRH) and histidyl-proline
      diketopiperazine [cyclo (His-Pro), CHP] on amylase secretion from isolated rat
      exocrine pancreatic acinar cells was investigated. TRH showed a dose-dependent
      inhibition of carbachol-stimulated amylase secretion with a maximum of 24% at a
      concentration of 10(-11) M (p < 0.05). Basal amylase release was not affected in
      concentrations from 10(13) M to 10(-8) M. CHP did not influence basal or
      carbachol-stimulated pancreatic secretion in vitro. These results suggest that
      TRH in contrast to CHP may play a role in the paracrine regulation of exocrine
      pancreatic secretion.

PMID- 7523821
TI  - Inhibition by tranilast of collagen accumulation in hypersensitive granulomatous
      inflammation in vivo and of morphological changes and functions of fibroblasts in
      vitro.
AB  - We examined the effects of tranilast, an anti-allergic agent, on hypersensitive
      inflammation and on morphology and functions of fibroblasts. In vivo, tranilast
      suppressed the content of collagen in granulation tissue of hypersensitive
      granulomatous inflammation induced by methylated bovine serum albumin (m-BSA) in
      rats. In culture, tranilast inhibited the TGF-beta-independent inflammatory
      exudate-induced stimulation of morphological changes of fibroblasts to
      myofibroblast-like cells and their proliferation. Collagen gel contraction by
      myofibroblast-like cells and fibroblasts was also inhibited by tranilast. Flow
      cytometric analysis revealed that tranilast suspended the cell cycle of
      fibroblasts at the G0/G1 phase. These results suggest that tranilast modulates
      the fibrosis and contraction of granulation tissue by inhibiting the growth of
      myofibroblast-like cells and fibroblasts.

PMID- 7523825
TI  - Morphogenesis-independent regulation of actin transcript levels in the pathogenic
      yeast Candida albicans.
AB  - The transcript level of the Candida albicans ACT1 gene (encoding actin) is
      strongly regulated during induction of hyphal morphogenesis. ACT1 mRNA declines
      rapidly during starvation pretreatment and quickly recovers in media inducing
      morphogenesis. The C. albicans URA3 and LEU2 mRNAs, as well as an ACT1
      promoter/LAC4 fusion, are regulated similarly. The regulation of ACT1/LAC4 and
      unaltered mRNA stabilities suggest transcriptional regulation during
      morphogenesis. However, by individually testing morphogenesis induction
      parameters, it is shown that starvation and growth phase, but not hyphal
      formation, are responsible for ACT1 transcript regulation; this conclusion is
      confirmed by analyses of morphological mutants and by inhibition of hyphal
      development. Thus, the specific morphogenesis-induction conditions, but not
      morphogenesis per se, affect transcript levels in C. albicans.

PMID- 7523823
TI  - Prenatal ethanol exposure affects the activity and mRNA expression of neuronal
      membrane enzymes in rat offspring.
AB  - In order to elucidate molecular mechanisms underlying brain dysfunction in
      offspring exposed to ethanol in utero, subclinical doses of ethanol that do not
      have apparent structural effect on the offspring were administered
      intraperitoneally to pregnant rats at various gestational stages. We measured the
      activity of membrane marker enzymes and the level of mRNA of myelin proteins of
      the offspring brain. The activity of a myelin specific enzyme, 2',3'-cyclic
      nucleotide 3'-phosphodiesterase (CNP) decreased in ethanol-exposed offspring.
      This effect was not related to the period of gestation or the dose of ethanol.
      Perikaryonal enzymes, acetylcholinesterase and Na+, K(+)-ATPase, were
      significantly affected in groups exposed to ethanol at early fetal stage and in
      high doses. Expression of mRNAs of CNP and myelin basic proteins decreased
      significantly in the ethanol-treated group, with abnormal developmental profile
      suggesting a relationship with delayed myelination in offspring exposed to
      ethanol in utero. The present findings suggest that in spite of the low doses of
      ethanol that do not cause clinical symptoms in the offspring, prenatal exposure
      to ethanol affects the level of mRNA of membrane enzyme proteins in the offspring
      brain, consequently causing a corresponding reduction in enzyme activity, that
      may lead to neuronal dysfunction. In a separate study, blood ethanol levels were
      found to reach a maximum level within 30 min after injection and be undetectable
      after 5 to 10 h. No accumulation effects due to daily injection were observed.

PMID- 7523820
TI  - [Chemotherapy and radiochemotherapy of colorectal cancers: adjuvant and
      palliative therapeutic procedures].
AB  - Palliative treatment in metastatic colorectal carcinoma is primarily based on 5
      fluorouracil. The remission rates have been improved by biomodulation and by
      continuous infusion of 5-FU. Adjuvant treatment for carcinoma of the colon and
      rectum is used in subgroups of patients in order to improve the results of
      surgical treatment. After curative resection of a colonic carcinoma with lymph
      node metastasis (TNM stage III) treatment with levamisole and 5-FU is indicated.
      As the risk of local failure is increased in carcinoma of the rectum adjuvant
      pelvic radiation therapy is used, eventually combined with systemic chemotherapy.
      In order to define the subgroups of patients who might profit by palliative or
      adjuvant treatment and in order to develop more effective combination therapies
      patients should be entered into prospective randomized trials.

PMID- 7523824
TI  - 26th Bethesda conference: recommendations for determining eligibility for
      competition in athletes with cardiovascular abnormalities. Task Force 6:
      arrhythmias.

PMID- 7523822
TI  - Role of B1 and B2 receptors and of nitric oxide in bradykinin-induced relaxation
      and contraction of isolated rat duodenum.
AB  - Bradykinin (BK) and its analogues induce a typical biphasic response (relaxation
      followed by contraction) in the isolated rat duodenum. We studied the role of B1
      and B2 BK receptors and nitric oxide (NO) in relaxation and contraction of the
      isolated rat duodenum. Both effects are concentration-dependent: BK has shown an
      EC50 (contraction) of 3.8 +/- 1.9 x 10(-7) M and an IC50 (relaxation) of 3.0 +/-
      0.7 x 10(-9). Similar results were obtained with the selective B2 receptor
      agonists [Hyp3,Tyr(Me)8]-BK and [Phe8 psi (CH2-NH)Arg9]-BK, showing an EC50 of
      9.6 +/- 1.9 x 10(-7) M and 5.6 +/- 2.9 x 10(-7) M and an IC50 of 3.5 +/- 0.6 x
      10(-10) M and 6.8 +/- 1.7 x 10(-10) M, respectively. Furthermore, the effects
      induced by these three agonists were not altered when tissues were treated with
      42.1 microM Mergetpa, a carboxypeptidase N inhibitor. While the relaxant and
      contractile effects elicited by BK were significantly inhibited in the presence
      of Hoe 140 (0.7 microM), a selective B2 receptor antagonist, those induced by the
      selective B1 receptor agonist desArg9-BK were not. Furthermore, [Leu8]-desArg9-BK
      (2.6 microM), which is both a pure and selective B1 receptor antagonist, acted as
      an agonist on the rat duodenum, inducing a biphasic relaxant and contractile
      effect. These relaxant and contractile effects were not altered by drugs that
      inhibit or stimulate NO production, such as L-NAME (200 microM), a combination of
      L-NAME (200 microM) and indomethacin (2.5 microM), L-arginine (1 mM), or
      superoxide dismutase (20 U/ml). However, the contractile effect was significantly
      reduced when tissues were preincubated with methylene blue (100 microM), which
      inhibits activation of guanylate cyclase. We conclude that 1) BK and its
      analogues selectively activate a B2 receptor, producing a biphasic effect
      (relaxation and contraction); 2) DesArg9-BK may either acts via a different
      receptor which might be another B1 receptor subtype or a typical B1 receptor
      where [Leu8]-desArg9-BK acts as a partial agonist; and 3) neither NO nor the
      prostaglandin pathway mediates BK-induced relaxation in the isolated rat
      duodenum.

PMID- 7523826
TI  - The genus-specific lipopolysaccharide epitope of Chlamydia is assembled in C.
      psittaci and C. trachomatis by glycosyltransferases of low homology.
AB  - Chlamydiae possess a genus-specific epitope that is located on the
      lipopolysaccharide (LPS) and is composed of a 3-deoxy-D-manno-octulosonic acid
      (Kdo) trisaccharide of the sequence alpha Kdo-(2-->8)--alpha Kdo-(2-->4)-alpha
      Kdo. In Chlamydia trachomatis, this trisaccharide is biosynthetically generated
      through the action of a multi-functional Kdo-transferase encoded by the gene
      gseA. gseA of Chlamydia psittaci 6BC was cloned and expressed in a rough mutant
      (Re chemotype) of Escherichia coli (strain F515) that contains an LPS with only
      two alpha 2-->4-linked Kdo residues. Recombinant strains were able to add the
      immunodominant Kdo residue in alpha 2-->8-linkage to the parental LPS, as
      determined by SDS-PAGE and Western blot analysis using a monoclonal antibody
      against the genus-specific epitope. The DNA sequence of gseA was determined and
      aligned to that published recently for C. trachomatis serovar L2. Most
      surprisingly, the two deduced amino acid sequences shared only an overall
      homology of 67%. Thus, gseA exhibits species specificity at the DNA level,
      whereas its gene product results in the synthesis of a carbohydrate antigen with
      genus specificity.

PMID- 7523827
TI  - The regulatory RNA gene micF is present in several species of gram-negative
      bacteria and is phylogenetically conserved.
AB  - micF RNA post-transcriptionally regulates Escherichia coli outer membrane protein
      F (OmpF), in response to temperature increase and other environmental stress
      conditions, by binding to ompF mRNA and destabilizing the message. Southern
      analyses show that the micF gene is present in related Gram-negative bacteria,
      including Salmonella typhimurium, Klebsiella pneumoniae, and Pseudomonas
      aeruginosa. In addition, Northern analyses indicate that micF RNA and ompF mRNA
      levels are thermally regulated in several related species in a manner similar to
      the thermoregulation in Escherichia coli. DNA sequences from Salmonella typhi,
      Salmonella typhimurium, and Klebsiella pneumoniae show greater than 96% homology
      in the micF gene when compared to the Escherichia coli micF sequence. Upstream of
      micF, sequences show considerable variation, although several distinct regions
      are highly conserved. Some of these conserved regions correspond to known binding
      sites for the transcription factor OmpR and the DNA-binding protein integration
      host factor. In addition, E. coli micF RNA incubated with protein extracts from
      other species forms heterologous ribonucleoproteins (RNPs). The formation of
      these heterologous RNPs indicates both the presence of micF RNA-binding protein
      homologues in other species and a conservation of RNA-protein recognition sites.
      This work demonstrates that the micF RNA regulatory system is present in other
      Gram-negative bacterial species and that this system appears to be
      phylogenetically conserved.

PMID- 7523828
TI  - Streptococcus pyogenes type IIa IgG Fc receptor expression is co-ordinately
      regulated with M protein and streptococcal C5a peptidase.
AB  - Streptococcus pyogenes is an important agent of human disease which expresses a
      variety of proteins and polysaccharides on its surface. Surface molecules M
      protein and streptococcal C5a peptidase (SCPA) are virulence factors which
      undergo concurrent phase variation and are under the co-ordinate control of the
      virR locus. Most opacity factor-positive (OF+) strains of S. pyogenes also
      express IgG Fc receptor proteins on their surface. These studies were initiated
      to determine whether the type IIa Fc receptor on the surface of S. pyogenes phase
      varies with members of this regulatory circuit. Several methods were applied to
      M+ and M- variant strains to evaluate this question. (i) Immunoblot assays
      quantified Fc receptors on whole cells by using human IgG myeloma protein and
      receptor-specific antibody. M+ strains bound IgG and antibody specific for Fc
      protein, whereas M- strains did not. (ii) Enzyme-linked immunosorbent assays
      quantified Fc receptor antigen expression and showed that M+ strains produce more
      Fc receptor protein than their M- derivatives. (iii) Quantitative RNA dot blots
      showed that the message for the Fc receptor gene (fcrA) was reduced in M-
      strains. RNA from M+ strains hybridized to the fcrA probe at a greater dilution
      than that from their M- counterparts. (iv) Northern hybridization showed that the
      fcrA transcript is 1200 nucleotides in size and distinct from transcripts for M
      and SCPA proteins. These data are evidence for the co-ordinate transcriptional
      control of the Fc receptor, M protein, and SCPA and show that these proteins co
      ordinately phase-vary within the same regulatory circuit.

PMID- 7523829
TI  - Peptide permeases modulate transformation in Streptococcus pneumoniae.
AB  - To identify elements participating in the process of transformation, a bank of
      genetically altered mutants of Streptococcus pneumoniae with defects in exported
      proteins was assessed for a decrease in transformation efficiency. One mutant
      consistently transformed 10-fold less than the parent strain. Sequence analysis
      and reconstitution of the altered locus revealed a gene, plpA (permease-like
      protein), which encodes a putative substrate-binding protein belonging to the
      family of bacterial permeases responsible for peptide transport. The derived
      amino acid sequence for this gene was 80% similar to AmiA, a peptide-binding
      protein homologue from pneumococcus, and 50% similar over 230 amino acids to
      Spo0KA which is a regulatory element in the process of transformation and
      sporulation in Bacillus subtilis. PlpA fusions to alkaline phosphatase (PhoA)
      were shown to be membrane associated and labelled with [3H]-palmitic acid, which
      probably serves as a membrane anchor. Experiments designed to define the roles of
      the plpA and ami determinants in the process of transformation showed that: (i)
      mutants with defects in plpA were > 90% transformation deficient while ami
      mutants exhibited up to a fourfold increase in transformation efficiency; (ii)
      compared to the parental strain, the onset of competence in an ami mutant
      occurred earlier in logarithmic growth, whereas the onset was delayed in a plpA
      mutant; and (iii) the plpA mutation decreases the expression of a competence
      regulated locus. Since the permease mutants would fail to bind specific ligands,
      it seems likely that the substrate-permease interaction modulates the process of
      transformation.

PMID- 7523830
TI  - Tyrosine kinase activity in Pseudomonas aeruginosa.
AB  - Previous evidence showed that b- and a-type flagellins of Pseudomonas aeruginosa
      are modified in vivo by phosphorylation at tyrosine. This research was designed
      to demonstrate phosphorylation of flagellin at tyrosine in vitro. Evidence
      presented showed that flagellin is labelled by [gamma-32P]-ATP, but not by [alpha
      32P]-ATP, when incubated with cell envelope fractions. Results suggested that
      autophosphorylation of a 42 kDa membrane protein occurred. No activity was
      detected in cytoplasmic fractions. Flagellin protein was identified by flagella
      specific monoclonal antibody (mAb) and was labelled with anti-phosphotyrosine
      mAb. Confirmation of tyrosine kinase activity was shown by labelling of synthetic
      poly(Glu:Tyr) as a substrate with [gamma-32P]-ATP. Labelling of poly(Glu:Tyr) was
      heat sensitive and time dependent. Labelled phosphotyrosine was observed in
      partial acid hydrolysates of substrates. Using poly(Glu:Tyr) as substrate,
      tyrosine kinase activity was shown to be inhibited by sulphydryl reagents. It
      appears that tyrosine kinase and flagellin phosphorylation occur in several
      Pseudomonas spp. Location of phosphotyrosine in a conserved region of flagellin
      may serve as a cell signal so that intact flagellin is appropriately exported.

PMID- 7523832
TI  - Aeromonas spp. can secrete Escherichia coli alkaline phosphatase into the culture
      supernatant, and its release requires a functional general secretion pathway.
AB  - Aerolysin is a channel-forming protein secreted by Aeromonas hydrophila. To
      determine if regions of aerolysin could direct the secretion of another protein,
      portions of aerA were fused to phoA, the Escherichia coli alkaline phosphatase
      gene and cloned into E. coli, Aeromonas salmonicida, and A. hydrophila. We were
      surprised to find that secretion of the enzyme by both Aeromonas spp. was
      independent of the aerolysin segments fused to it. The smallest fusion product
      contained only the signal sequence and two amino acids of aerolysin. The largest
      had more than 90% of the aerolysin molecule. The fusion proteins were found in
      the periplasms of E. coli and A. salmonicida grown in LB medium containing
      glucose, as well as in the shocked cells. Aerolysin itself was secreted by A.
      salmonicida under these conditions. In contrast, when A. salmonicida containing
      any of the fused genes was grown in LB medium without glucose, most of the
      alkaline phosphatase activity was extracellular, whereas beta-lactamase remained
      in its normal periplasmic location. Similar results were obtained with A.
      hydrophila. The change in location of the enzyme in A. salmonicida appeared to be
      related to the pH of the growth medium. A. salmonicida and A. hydrophila also
      secreted native E. coli alkaline phosphatase, but A. hydrophila strains with
      mutations in the general secretion pathway were unable to release the enzyme. We
      conclude that the Aeromonas secretion system can recognize the E. coli enzyme as
      an extracellular protein and direct it outside the cell.

PMID- 7523833
TI  - PcnB is required for the rapid degradation of RNAI, the antisense RNA that
      controls the copy number of ColE1-related plasmids.
AB  - The replication of ColE1-related plasmids is controlled by an unstable antisense
      RNA, RNAI, which can interfere with the successful processing of the RNAII primer
      of replication. We show here that a host protein, PcnB, supports replication by
      promoting the decay of RNAI. In bacterial strains deleted for PcnB a stable,
      active form of RNAI, RNAI*, which appears to be identical to the product of 5'
      end processing by RNAase E, accumulates. This leads to a reduction in plasmid
      copy number. We show, using a GST-PcnB fusion protein, that PcnB does not
      interfere with RNAI/RNAII binding in vitro. The fusion protein, like PcnB, has
      polyadenylating activity and is able to polyadenylate RNAI (and also another
      antisense RNA, CopA) in vitro.

PMID- 7523831
TI  - ColE1 multimer formation triggers inhibition of Escherichia coli cell division.
AB  - Multimer formation and consequent copy number depression are acknowledged causes
      of multicopy plasmid instability. Multimer resolution sites (among which ColE1
      cer is best-characterized) have been identified in a variety of plasmids. They
      participate in the conversion of multimers to monomers, maximizing the number of
      independently segregating molecules and minimizing the frequency of plasmid loss.
      We show that multimer resolution alone is insufficient to ensure stable
      maintenance of ColE1-like plasmids in a recombination-proficient host. The
      expression of Rcd, a transcript encoded within cer and expressed in multimer
      containing cells, is also required. The appearance of Rcd correlates with the
      inhibition of division of multimer-containing cells, presumably allowing time for
      the conversion of multimers to monomers by site-specific recombination.

PMID- 7523834
TI  - The role of a repetitive DNA motif (5'-CAAT-3') in the variable expression of the
      Haemophilus influenzae lipopolysaccharide epitope alpha Gal(1-4)beta Gal.
AB  - Haemophilus influenzae lipopolysaccharide (LPS) contains structures, defined by
      monoclonal antibodies, which undergo phase variation. This investigation reports
      the nucleotide sequence of lic2A, which is required for the expression of at
      least three phase-variable LPS epitopes, one of which has the structure alpha
      Gal(1-4)beta Gal. lic2A contains multiple tandem repeats of the tetramer 5'-CAAT
      3'. Previous studies have correlated changes in the number of 5'-CAAT-3' repeats
      with the phase-variable expression of the alpha Gal(1-4)beta Gal epitope. To
      obtain direct evidence for this, the 5'-CAAT-3' repeat region from lic2A was
      amplified directly from immunostained colonies and sequenced. This demonstrated
      that the variable expression of LPS epitopes, including alpha Gal(1-4)beta Gal,
      is in part directly dependent upon the number of copies of 5'-CAAT-3' within
      lic2A.

PMID- 7523835
TI  - Synaptonemal complex aberrations in the pseudoautosomal region of X, Y
      chromosomes in irradiated hamsters.
AB  - The effects of X-radiation, bleomycin and amsacrine (m-AMSA) on the meiotic
      chromosomes of male Armenian hamsters were determined by electron microscopic
      analysis of synaptonemal complex (SC) damage. Pachytene stage cells were analyzed
      5 or 6 days following their treatment at putative preleptotene-leptotene stages
      of meiosis. Of the multiple types of SC aberrations observed to be significantly
      increased over control levels, lateral element breakage and synaptic anomalies
      were most prevalent. The focus of these studies was on the sex chromosomes which,
      in the Armenian hamster, reveal an unusually well-defined pseudoautosomal region.
      In the XY pair, radiation and chemical treatments caused certain forms of
      structural and synaptic anomalies which appeared to be preferentially localized
      to telomeric and/or crossover regions. The nature of these specific aberrations,
      involving breakage, bridge formation and asynapsis, is not well understood;
      however, their distributions are suggestive of possible relationships with sites
      and processes of crossing over.

PMID- 7523836
TI  - Design of degenerate oligonucleotide primers for cloning of G-protein alpha
      subunits.

PMID- 7523837
TI  - Purification and characterization of membrane protein (90 kDa) from Mycoplasma
      salivarium, which binds immunoglobulin (Ig) G Fc fragment.
AB  - A 90 kDa protein of Mycoplasma salivarium was released from cell membranes of the
      organism with Triton X-100 and purified by ion-exchange chromatography and
      chromatofocusing. The protein was eluted at pH 5.5 by chromatofocusing. The
      protein was shown to react with the Fc fragments of IgG from human and nine
      different animal species and did not distinguish between IgG from different
      species, while protein A, tested for comparative purposes, displayed a strong
      specificity for human and swine IgG. Furthermore, the protein reacted with
      antigen specific goat IgG (specific for gamma chains of human IgG), sheep red
      blood cells (SRBC) sensitized with rabbit antiserum to SRBC, that is, the Fc part
      of rabbit IgG, and concanavalin A as well. These findings may suggest that the
      protein is a lectin which binds the carbohydrate moiety of the Fc part of IgG.

PMID- 7523838
TI  - Modulation by polymyxin B of the effects of interferon on human myelogenous
      leukemia cells.
AB  - Natural and recombinant human interferon-alpha (IFN-alpha) and -gamma (IFN-gamma)
      exert differentiation-inducing and cytocidal effects in vitro on cells of the
      human myeloblastic leukemia cell line ML-2. These activities of IFNs are
      modulated by polymyxin B (PMB), a cyclic polycationic peptide antibiotic
      effective on Gram-negative bacilli. The modulating effect of PMB varies according
      to the species of IFN, namely, PMB enhances the activities of either natural IFN
      gamma or recombinant IFN-gamma, while it inhibits the effects of either natural
      IFN-alpha or recombinant IFN-alpha. The cause of this variety in PMB effect on
      IFNs remains to be clarified.

PMID- 7523839
TI  - Melatonin increases cyclic guanosine monophosphate: biochemical effects mediated
      by porphyrins, calcium and nitric oxide. Relationships to infant colic and the
      Sudden Infant Death Syndrome.
AB  - It is hypothesized that melatonin, by its actions on porphyrin and nitric oxide
      biosynthesis, produces an increase in cyclic guanosine monophosphate.

PMID- 7523841
TI  - [Benign prostatic hyperplasia. Therapeutic possibilities].

PMID- 7523840
TI  - Amyotrophic lateral sclerosis: hypothetical pathogenesis.
AB  - A hypothetical pathogenesis for a typical case of amyotrophic lateral sclerosis
      (ALS) follows from opinions of Rowland and results of neuroscientists at Baylor.
      ALS might typically result from an autoimmune disorder that causes IgG to enhance
      release of acetylcholine (ACh) from axon terminals. Motor neuron overactivity
      associated with fasciculation might result from enhanced release of ACh which is
      taken up by nicotinic ACh receptors. Increased levels of intracellular calcium
      ions might result from motor neuron overactivity associated with fasciculation.
      Neuronal cell degeneration and death might result from increased levels of
      intracellular calcium ions.

PMID- 7523843
TI  - [Change in the course of drug therapy of hyperthyroidism?].

PMID- 7523842
TI  - [A luminescence microscopy method for studying organ function in Aspiculuris
      tetraptera (Schulz, 1924)].
AB  - The paper proposes the rapid technique for examining the luminescence pattern of
      individual systems and organs in the murine parasite Aspiculuris tetraptera. The
      luminescence pattern of the parasite was studied after fluorochrome-plating with
      rhodamine 6G, rhodamine C, coryphosphine, sodium fluorescein, acridine orange
      which was found to be the optimum fluorochrome. This technique is to be used in
      the evaluation of the effects of chemopharmaceuticals on the parasite.

PMID- 7523844
TI  - Operating room allocations, scheduling and the anesthesiologist.

PMID- 7523845
TI  - Resistance to atracurium: Wegener's granulomatosis--a case report.
AB  - Few previous reports clarified that patients with an increased alpha 1 globulin
      fraction in their serum protein electrophoresis, will have resistance to the
      neuromuscular block of atracurium. Having a patient with diagnosis of Wegener's
      granulomatosis and a marked elevation of alpha 1 globulin fraction in her
      electrophoresis, we took this opportunity to monitor the neuromuscular block of
      atracurium. The data obtained, confirm previous studies showing that patients
      with a marked increase in alpha 1 globulin fraction may have a resistance to the
      action of atracurium.

PMID- 7523846
TI  - Consequences of lead exposure and iron supplementation on childhood development
      at age 4 years.
AB  - For a prospective study of lead exposure and early development, we recruited
      pregnant women from a smelter town and a nonlead-exposed town in Yugoslavia and
      followed them and their children through age 4. For 332 children seen at age 4,
      mean scores on the McCarthy Scales General Cognitive Index (GCI) in the exposed
      and nonexposed towns were 81.3 and 86.6, respectively; geometric mean blood lead
      concentrations (BPb) were 39.9 and 9.6 micrograms/dl, respectively. Potential
      confounders included the quality of the HOME environment; maternal age,
      intelligence, education, and language; birthweight and gender. These showed
      predictable associations with 4-year intelligence, accounting for 42.7% of the
      variance in GCI. Following adjustment for these variables and for concurrent Hgb,
      we found significant independent adverse associations between GCI and BPb's,
      measured at 6-month intervals since birth. At age 4, BPb accounted for an
      incremental 3.5% of the variance in GCI, such that the estimated loss in GCI
      associated with an increase in BPb from 10-25 micrograms/dl was 3.8 points. The
      Perceptual-Performance subscale of the McCarthy was most sensitive to Pb
      exposure, a result consistent with findings from prospective studies in Boston
      and Port Pirie.

PMID- 7523847
TI  - Interleukin-8 activates microtubule-associated protein 2 kinase (ERK1) in human
      neutrophils.
AB  - The signal transduction initiated by the human cytokine interleukin-8 (IL-8), the
      main chemotactic cytokine for neutrophils, was investigated and found to
      encompass the stimulation of protein kinases. More specifically, IL-8 caused a
      transient, dose and time dependent activation of a Ser/Thr kinase activity
      towards myelin basic protein (MBP) and the MBP-derived peptide APRTPGGRR
      patterned after the specific concensus sequence in MBP for ERK enzymes. The
      activated MBP kinase was furthermore identified as an extracellular signal
      regulated kinase (ERK1) based on several criteria such as substrate specificity,
      molecular weight, activation-dependent mobility shift, and recognition by anti
      ERK antibodies. For comparison, the chemotactic response of neutrophils to a
      stimulus of bacterial origin (fMet-Leu-Phe or fMLP) was also examined and found
      to involve the activation of a similar ERK enzyme. The present data clearly
      indicate that in terminally differentiated, non-proliferating human cells, the
      MBP kinase/ERK activity can serve other purposes than mitogenic signaling, and
      that processes such as chemotaxis, induced by bacterial peptides as well as by
      human cytokines like IL-8, involve the regulation of ERK enzymes.

PMID- 7523848
TI  - Does the insulin-mimetic action of vanadate involve insulin receptor kinase?
AB  - Effects of vanadate administration on the insulin receptor status in liver were
      examined in streptozotocin-induced diabetic rats. Diabetic rats were
      characterized by hyperglycemia (4-fold increase), hypoinsulinemia (81% decrease)
      and a significant (P < 0.01) increase in hepatic insulin receptor numbers.
      Autophosphorylation of the beta subunit of insulin receptor and its tyrosine
      kinase activity towards the synthetic peptide (poly glut4tyr1) decreased by
      approximately 60% as a result of diabetes. After chronic treatment of these rats
      with sodium orthovanadate, the plasma glucose levels were normalized to near
      control values with the hypoinsulinemia remaining unaltered. The insulin
      stimulated phosphorylation of the beta subunit increased significantly (P <
      0.001) in diabetic rats after treatment with vanadate. However, the improvement
      in the tyrosine kinase activity was marginal. In vitro, vanadate prevented the
      dephosphorylation of the phosphorylated insulin receptor and increased its
      tyrosine kinase activity in the absence as well as presence of insulin. The
      findings of this study further support the view that insulin receptor is one of
      the sites involved in the insulin-mimetic actions of vanadate.

PMID- 7523849
TI  - Evidence for an extra-cellular function for protein kinase A.
AB  - In addition to its intra-cellular functions, cAMP-dependent protein kinase (PKA)
      may well have an extra-cellular regulatory role in blood. This suggestion is
      based on the following experimental findings: (a) Physiological stimulation of
      blood platelets brings about a specific release of PKA, together with its co
      substrates ATP and Mg++; (b) In human serum, an endogenous phosphorylation of one
      protein (p75, M(r) 75 kDa) occurs; this phosphorylation is enhanced by addition
      of cAMP and blocked by the Walsh-Krebs specific PKA inhibitor; (c) No endogenous
      phosphorylation of p75 occurs in human plasma devoid of platelets, but the
      selective labeling of p75 can be reproduced by adding to plasma the pure
      catalytic subunit of PKA; (d) p75 was shown to be vitronectin (V), a
      multifunctional protein implicated in processes associated with platelet
      activation, and thus a protein whose function may require modulation for control;
      (e) The phosphorylation of vitronectin occurs at one site (Ser378) which, at
      physiological pH, is buried in its two-chain form (V65 + 10) but it becomes
      'exposed' in the presence of glycosaminoglycans (GAGs) e.g. heparin or heparan
      sulfate. Such a transconformation may be used for targeting the PKA
      phosphorylation to vitronectin molecules bound to GAGs, for example in the
      extracellular matrix or on cell surfaces; (f) From the biochemical point of view
      (Km values and physiological concentrations) the phosphorylation of vitronectin
      can take place at the locus of a hemostatic event; (g) The phosphorylation of
      Ser378 in vitronectin alters its function, since it significantly reduces its
      ability to bind the inhibitor-1 of plasminogen activator(s) (PAI-1).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7523850
TI  - A mitochondrial retroplasmid integrates into mitochondrial DNA by a novel
      mechanism involving the synthesis of a hybrid cDNA and homologous recombination.
AB  - The Mauriceville and Varkud mitochondrial plasmids of Neurospora spp. are closely
      related, small circular DNAs that propagate via an RNA intermediate and reverse
      transcription. Although the plasmids ordinarily replicate autonomously, they can
      also integrate into mitochondrial DNA (mtDNA), yielding defective mtDNAs that in
      some cases cause senescence. To investigate the integration mechanism, we
      analyzed four cases in which the Varkud plasmid integrated into the mitochondrial
      small rRNA gene, three in wild-type subcultures and one in a senescent mutant.
      Our analysis suggests that the integrations occurred by the plasmid reverse
      transcriptase template switching between the plasmid transcript and internal
      sequences in the mitochondrial small rRNA to yield hybrid cDNAs that circularized
      and recombined homologously with the mtDNA. The integrated plasmid sequences are
      transcribed, presumably from the mitochondrial small rRNA promoters, resulting in
      hybrid RNAs containing the 5' segment of the mitochondrial small rRNA linked head
      to-tail to the full-length plasmid transcript. Analysis of additional senescent
      mutants revealed three cases in which the plasmid used the same mechanism to
      integrate at other locations in the mtDNA. In these cases, circular variant
      plasmids that had incorporated a mitochondrial tRNA or tRNA-like sequence by
      template switching integrated by homologous recombination at the site of the
      corresponding tRNA or tRNA-like sequence in mtDNA. This simple integration
      mechanism involving template switching to generate a hybrid cDNA that integrates
      homologously could have been used by primitive retroelements prior to the
      acquisition of a specialized integration machinery.

PMID- 7523851
TI  - A striking similarity in the organization of the E-selectin and beta interferon
      gene promoters.
AB  - Transcription of the endothelial leukocyte adhesion molecule 1 (E-selectin or
      ELAM-1) gene is induced by the inflammatory cytokines interleukin-1 beta and
      tumor necrosis factor alpha (TNF-alpha). In this report, we identify four
      positive regulatory domains (PDI to PDIV) in the E-selectin promoter that are
      required for maximal levels of TNF-alpha induction in endothelial cells. In vitro
      DNA binding studies reveal that two of the domains contain novel adjacent binding
      sites for the transcription factor NF-kappa B (PDIII and PDIV), a third
      corresponds to a recently described CRE/ATF site (PDII), and a fourth is a
      consensus NF-kappa B site (PDI). Mutations that decrease the binding of NF-kappa
      B to any one of the NF-kappa B binding sites in vitro abolished cytokine-induced
      E-selectin gene expression in vivo. Previous studies demonstrated a similar
      correlation between ATF binding to PDII and E-selectin gene expression. Here we
      show that the high-mobility-group protein I(Y) [HMG I(Y)] also binds specifically
      to the E-selectin promoter and thereby enhances the binding of both ATF-2 and NF
      kappa B to the E-selectin promoter in vitro. Moreover, mutations that interfere
      with HMG I(Y) binding decrease the level of cytokine-induced E-selectin
      expression. The organization of the TNF-alpha-inducible element of the E-selectin
      promoter is remarkably similar to that of the virus-inducible promoter of the
      human beta interferon gene in that both promoters require NF-kappa B, ATF-2, and
      HMG I(Y). We propose that HMG I(Y) functions as a key architectural component in
      the assembly of inducible transcription activation complexes on both promoters.

PMID- 7523852
TI  - Mouse alpha-fetoprotein gene 5' regulatory elements are required for postnatal
      regulation by raf and Rif.
AB  - The mouse alpha-fetoprotein (AFP) gene is expressed at high levels in the yolk
      sac and fetal liver and at low levels in the fetal gut. AFP synthesis decreases
      dramatically shortly after birth to low levels that are maintained in the adult
      liver and gut. AFP expression can be reactivated in the adult liver upon renewed
      cell proliferation such as during liver regeneration or in hepatocellular
      carcinomas. Previously, two unlinked genetic loci that modulate postnatal AFP
      levels were identified. The raf locus controls, at least in part, basal steady
      state AFP mRNA levels in adult liver. Rif influences the extent of AFP mRNA
      induction during liver regeneration. Transgenic mice were used to examine the
      role of 5' AFP regulatory regions in raf- and Rif-mediated control. A fragment of
      the AFP 5' region containing enhancer element I, the repressor, and the promoter
      was linked to the mouse class I H-2Dd structural gene. We demonstrate that this
      hybrid AFP-Dd transgene is expressed in the appropriate tissues. In addition, it
      is postnatally repressed and reactivated during liver regeneration in parallel
      with the endogenous AFP gene. Therefore, proper transcriptional control does not
      require the AFP structural gene. Furthermore, the AFP 5' control region is
      sufficient to confer raf and Rif responsiveness to the linked H-2Dd structural
      gene, suggesting that raf and Rif act at the level of transcriptional initiation.

PMID- 7523853
TI  - Methylation-related chromatin structure is associated with exclusion of
      transcription factors from and suppressed expression of the O-6-methylguanine DNA
      methyltransferase gene in human glioma cell lines.
AB  - There is considerable interest in identifying factors responsible for expression
      of the O-6-methylguanine DNA methyltransferase (MGMT) gene, as MGMT is a major
      determinant in the response of glioma cells to the chemotherapeutic agent 1,3
      bis(2-chloroethyl)-1-nitrosourea. Recently we have shown that MGMT expression is
      correlated in a direct, graded fashion with methylation in the body of the MGMT
      gene and in an inverse, graded fashion with promoter methylation in human glioma
      cell lines. To determine if promoter methylation is an important component of
      MGMT expression, this study addressed the complex interactions between
      methylation, chromatin structure, and in vivo transcription factor occupancy in
      the MGMT promoter of glioma cell lines with different levels of MGMT expression.
      Our results show that the basal promoter in MGMT-expressing glioma cell lines,
      which is 100% unmethylated, was very accessible to restriction enzymes at all
      sites tested, suggesting that this region may be nucleosome free. The basal
      promoter in glioma cells with minimal MGMT expression, however, which is 75%
      unmethylated, was much less accessible, and the basal promoter in nonexpressing
      cells, which is 50% unmethylated, was entirely inaccessible to restriction
      enzymes. Despite the presence of the relevant transcription factors in all cell
      lines examined, in vivo footprinting showed DNA-protein interactions at six Sp1
      binding sites and one novel binding site in MGMT-expressing cell lines but no
      such interactions in nonexpressors. We conclude that in contrast to findings of
      previous in vitro studies, Sp1 is an important component of MGMT transcription.
      These correlations also strongly suggest that methylation and chromatin
      structure, by determining whether Sp1 and other transcription factors can access
      the MGMT promoter, set the transcriptional state of the MGMT gene.

PMID- 7523854
TI  - Efficient homologous recombination of Ty1 element cDNA when integration is
      blocked.
AB  - Integration of the yeast retrotransposon Ty1 into the genome requires the self
      encoded integrase (IN) protein and specific terminal nucleotides present on full
      length Ty1 cDNA. Ty1 mutants with defects in IN, the conserved termini of Ty1
      cDNA, or priming plus-strand DNA synthesis, however, were still able to
      efficiently insert into the genome when the elements were expressed from the GAL1
      promoter present on a multicopy plasmid. As with normal transposition, formation
      of the exceptional insertions required an RNA intermediate, Ty1 reverse
      transcriptase, and Ty1 protease. In contrast to Ty1 transposition, at least 70%
      of the chromosomal insertions consisted of complex multimeric Ty1 elements. Ty1
      cDNA was transferred to the inducing plasmid as well as to the genome, and
      transfer required the recombination and repair gene RAD52. Furthermore,
      multimeric insertions occurred without altering the levels of total Ty1 RNA,
      virus-like particle-associated RNA or cDNA, Ty1 capsid proteins, or IN. These
      results suggest that Ty1 cDNA is utilized much more efficiently for homologous
      recombination when IN-mediated integration is blocked.

PMID- 7523856
TI  - A novel hepatocytic transcription factor that binds the alpha-fetoprotein
      promoter-linked coupling element.
AB  - We recently characterized a promoter-linked coupling element (PCE) in the rat
      alpha-fetoprotein (AFP) gene required for strong transcriptional stimulation by
      distant enhancers (P. Wen, N. Crawford, and J. Locker, Nucleic Acids Res. 21:1911
      1918, 1993). In this study, oligonucleotide gel retardation and competition
      experiments defined the PCE as a 12-bp binding site, TGTCCTTGAACA, an imperfect
      inverted repeat from -166 to -155 near the AFP promoter. A factor that bound this
      site (PCF) was abundant in HepG2 nuclear extracts and detectable in extracts from
      several other AFP-producing hepatocarcinoma cell lines and fetal liver.
      Hepatocytic cell lines that did not express AFP, nonhepatocytic cell lines, adult
      liver, and fetal brain did not show the factor. Experiments excluded the
      possibility that PCF activity was due to binding of glucocorticoid receptor or an
      AP1-like factor that bound overlapping sites. Competition experiments with
      several mutant oligonucleotides determined that the optimum PCF binding site was
      TGTCCTTGAAC(A/T). Mutations decreased binding or totally abolished binding
      activity. In expression plasmids, PCE mutations strongly reduced gene expression.
      UV cross-linking to a PCE probe identified peptide bands near 34 kDa. PCF was
      purified by heparin-Sepharose chromatography followed by affinity binding to
      oligomerized PCE DNA. The product resolved as a complex of three peptides (PCF
      alpha 1, PCF alpha 2, and PCF beta, 32 to 34 kDa) on sodium dodecyl sulfate
      acrylamide gels. The peptide sizes and gel patterns are unlike those of any of
      the well-described hepatic transcription factors, and the binding site has not
      been previously reported. PCF thus appears to be a novel transcription factor.

PMID- 7523855
TI  - Two FK506 resistance-conferring genes in Saccharomyces cerevisiae, TAT1 and TAT2,
      encode amino acid permeases mediating tyrosine and tryptophan uptake.
AB  - The macrocyclic lactone FK506 exerts immunosuppressive effects on T lymphocytes
      by interfering with signal transduction leading to T-cell activation and also
      inhibits the growth of eukaryotic microorganisms, including Saccharomyces
      cerevisiae. We reported previously that an FK506-sensitive target in S.
      cerevisiae is required for amino acid import and that overexpression of two new
      genes, TAT1 and TAT2 (formerly called TAP1 and TAP2), confers resistance to the
      drug. Here we report that TAT1 and TAT2 encode novel members of the yeast amino
      acid permease family composed of integral membrane proteins that share 30 to 40%
      identity. TAT1 is the tyrosine high-affinity transporter, which also mediates low
      affinity or low-capacity uptake of tryptophan. TAT2 is the tryptophan high
      affinity transporter. FK506 does not reduce the levels of TAT1 and TAT2
      transcripts, indicating that the inhibition of amino acid transport by the drug
      is posttranscriptional.

PMID- 7523858
TI  - The Fps/Fes protein-tyrosine kinase promotes angiogenesis in transgenic mice.
AB  - The fps/fes proto-oncogene encodes a cytoplasmic protein-tyrosine kinase known to
      be highly expressed in hematopoietic cells. To investigate fps/fes biological
      function, an activating mutation was introduced into the human fps/fes gene which
      directs amino-terminal myristylation of the Fps/Fes protein. This mutant,
      myristylated protein induced transformation of Rat-2 fibroblasts. The mutant
      fps/fes allele was incorporated into the mouse germ line and was found to be
      appropriately expressed in transgenic mice, in a tissue-specific pattern
      indistinguishable from that of the endogenous mouse gene. These mice displayed
      widespread hypervascularity, progressing to multifocal hemangiomas. High levels
      of both the transgenic human and endogenous murine fps/fes transcripts were
      detected in vascular tumors by using RNase protection, and fps/fes transcripts
      were localized to endothelial cells of both the vascular tumors and normal blood
      vessels by in situ RNA hybridization. Primary human umbilical vein endothelial
      cultures were also shown to express fps/fes transcripts and the Fps/Fes tyrosine
      kinase. These results indicate that fps/fes expression is intrinsic to cells of
      the vascular endothelial lineage and suggest a direct role of the Fps/Fes protein
      tyrosine kinase in the regulation of angiogenesis.

PMID- 7523857
TI  - Upstream tRNA genes are essential for expression of small nuclear and cytoplasmic
      RNA genes in trypanosomes.
AB  - An interesting feature of trypanosome genome organization involves genes
      transcribed by RNA polymerase III. The U6 small nuclear RNA (snRNA), U-snRNA B
      (the U3 snRNA homolog), and 7SL RNA genes are closely linked with different,
      divergently oriented tRNA genes. To test the hypothesis that this association is
      of functional significance, we generated deletion and block substitution mutants
      of all three small RNA genes and monitored their effects by transient expression
      in cultured insect-form cells of Trypanosoma brucei. In each case, two extragenic
      regulatory elements were mapped to the A and B boxes of the respective companion
      tRNA gene. In addition, the tRNA(Thr) gene, which is upstream of the U6 snRNA
      gene, was shown by two different tests to be expressed in T. brucei cells, thus
      confirming its identity as a gene. This association between tRNA and small RNA
      genes appears to be a general phenomenon in the family Trypanosomatidae, since it
      is also observed at the U6 snRNA loci in Leishmania pifanoi and Crithidia
      fasciculata and at the 7SL RNA locus in L. pifanoi. We propose that the A- and B
      box elements of small RNA-associated tRNA genes serve a dual role as intragenic
      promoter elements for the respective tRNA genes and as extragenic regulatory
      elements for the linked small RNA genes. The possible role of tRNA genes in
      regulating small RNA gene transcription is discussed.

PMID- 7523859
TI  - Multiple cytokines stimulate the binding of a common 145-kilodalton protein to
      Shc at the Grb2 recognition site of Shc.
AB  - We recently reported that interleukin-3, Steel factor, and erythropoietin all
      induce the tyrosine phosphorylation of Shc and its association with Grb2 in
      hemopoietic cell lines. We have now further characterized the proteins that
      become associated with Shc following stimulation with these cytokines and found
      that, in response to all three, the tyrosine-phosphorylated form of Shc binds to
      common 145- and 52-kDa proteins which also become tyrosine phosphorylated in
      response to these growth factors. The 145-kDa protein, which appears, from
      antiphosphotyrosine blots of two-dimensional O'Farrell gels, to exist in four
      different phosphorylation states following cytokine stimulation (with isoelectric
      points ranging from 7.2 to 7.8), does not appear to be immunologically related to
      the beta subunit of the interleukin-3 receptor, c-Kit, BCR, ABL, JAK1, JAK2,
      Sos1, eps15, or insulin receptor substrate 1 protein. Silver-stained sodium
      dodecyl sulfate gels indicate that the association of the 145-kDa protein with
      Shc occurs only after cytokine stimulation and that it can bind to the tyrosine
      phosphorylated form of Shc in its non-tyrosine-phosphorylated state. The latter
      finding, in conjunction with the observations that p145 does not bind, in vitro,
      to the Src homology 2 (SH2) domain of Shc, that it is not present in anti-Grb2
      immunoprecipitates, and that a phosphopeptide which blocks the binding of Shc to
      the SH2 domain of Grb2 also blocks the binding of Shc to p145, suggests that p145
      contains an SH2 domain and competes with Grb2 for the same tyrosine
      phosphorylated site on Shc. This implicates p145 as a potential regulator of Ras
      activity and, perhaps, of other as yet unidentified functions of Shc.

PMID- 7523861
TI  - Physical isolation of nascent RNA chains transcribed by RNA polymerase II:
      evidence for cotranscriptional splicing.
AB  - In order to examine whether splicing can occur cotranscriptionally in mammalian
      nuclei, we mapped exon-intron boundaries on nascent RNA chains transcribed by RNA
      polymerase II. A procedure that allows fractionation of nuclei into a chromatin
      pellet containing DNA, histones, and ternary transcription complexes and a
      supernatant containing the bulk of the nonhistone proteins and RNAs that are
      released from their DNA templates was developed. The transcripts of the genes
      encoding DBP, a transcriptional activator protein, and HMG coenzyme A reductase
      recovered from the chromatin pellet and the supernatant were analyzed by S1
      nuclease mapping. The large majority of the RNA molecules from the pellet
      appeared to be nascent transcripts, since, in contrast to the transcripts present
      in the supernatant, they were not cleaved at the polyadenylation site but rather
      contained heterogeneous 3' termini encompassing this site. Splicing intermediates
      could be detected among nascent and released transcripts, suggesting that
      splicing occurs both cotranscriptionally and posttranscriptionally. Our results
      also indicate that polyadenylation is not required for the splicing of the last
      DBP intron. In addition to allowing detailed structural analysis of nascent RNA
      chains, the physical isolation of nascent transcripts also yields reliable
      measurements of relative transcription rates.

PMID- 7523862
TI  - Tissue-specific regulation of mouse hepatocyte nuclear factor 4 expression.
AB  - Hepatocyte nuclear factor 4 (HNF-4) is a liver-enriched transcription factor and
      a member of the steroid hormone receptor superfamily. HNF-4 is required for the
      hepatoma-specific expression of HNF-1 alpha, another liver-enriched transcription
      factor, suggesting the early participation of HNF-4 in development. To prepare
      for further study of HNF-4 in development, the tissue-specific expression of the
      mouse HNF-4 gene was studied by analyzing the promoter region for required DNA
      elements. DNase-hypersensitive sites in the gene in liver and kidney tissues were
      found in regions both distal and proximal to the RNA start that were absent in
      tissues in which HNF-4 expression did not occur. By use of reporter constructs in
      transient-transfection assays and with transgenic mice, a region sufficient to
      drive liver-specific expression of HNF-4 was identified. While an HNF-1 binding
      site between bp -98 and -68 played an important role in the hepatoma-specific
      promoter activity of HNF-4 in transient-transfection assays, it was not
      sufficient for the liver-specific expression of a reporter gene in transgenic
      mice. Distal enhancer elements indicated by the presence of DNase I
      hypersensitive sites at kb -5.5 and -6.5, while not functional in transient
      transfection assays, were required for the correct expression of the mouse HNF-4
      gene in animals.

PMID- 7523860
TI  - A novel synapse-associated noncoding RNA.
AB  - Synaptic nuclei of innervated muscle transcribe acetylcholine receptor (AChR)
      genes at a much higher level than extrasynaptic nuclei. To isolate candidate
      synaptic regulatory molecules responsible for the unique transcriptional
      potential of synaptic nuclei, we have taken a subtractive hybridization approach.
      Here, we report the cloning and characterization of a novel synapse-associated
      RNA, 7H4. 7H4 is expressed selectively in the endplate zone of skeletal muscle
      and is upregulated during early postnatal development and after denervation.
      Interestingly, the 7H4 gene has no introns, and yet two different-size RNAs with
      identical polyadenylated 3' ends are generated. Most intriguingly, the nucleotide
      sequence does not contain any significant open reading frames, suggesting that
      7H4 may function as a noncoding RNA.

PMID- 7523863
TI  - Breakpoint junctions of chromosome 9p deletions in two human glioma cell lines.
AB  - Interstitial deletions of the short arm of chromosome 9 are associated with
      glioma, acute lymphoblastic leukemia, melanoma, mesothelioma, lung cancer, and
      bladder cancer. The distal breakpoints of the deletions (in relation to the
      centromere) in 14 glioma and leukemia cell lines have been mapped within the 400
      kb IFN gene cluster located at band 9p21. To obtain information about the
      mechanism of these deletions, we have isolated and analyzed the nucleotide
      sequences at the breakpoint junctions in two glioma-derived cell lines. The A1235
      cell line has a complex rearrangement of chromosome 9, including a deletion and
      an inversion that results in two breakpoint junctions. Both breakpoints of the
      distal inversion junction occurred within AT-rich regions. In the A172 cell line,
      a tandem heptamer repeat was found on either side of the deletion breakpoint
      junction. The distal breakpoint occurred 5' of IFNA2; the 256 bp sequenced from
      the proximal side of the breakpoint revealed 95% homology to long interspersed
      nuclear elements. One- and two-base-pair overlaps were observed at these
      junctions. The possible role of sequence overlaps, and repetitive sequences, in
      the rearrangement is discussed.

PMID- 7523864
TI  - Identification of cis-elements mediating the stimulation of rat insulin-like
      growth factor-binding protein-1 promoter activity by dexamethasone, cyclic
      adenosine 3',5'-monophosphate, and phorbol esters, and inhibition by insulin.
AB  - Insulin-like growth factor-binding protein-1 (IGFBP-1) modulates the action of
      IGFs on target cells. IGFBP-1 transcription is highly regulated by hormonal and
      metabolic factors. In rat H4-II-E hepatoma cells, IGFBP-1 messenger RNA is
      stimulated by dexamethasone, cAMP, and phorbol esters, and dominantly inhibited
      by insulin. To identify the cis-elements that determine transcriptional
      regulation by these agents, we have coupled rat IGFBP-1 promoter fragments to a
      luciferase reporter gene and transfected H4-II-E cells using the cationic
      liposome procedure. Promoter fragments whose 5'-end was at nucleotide (nt) -925
      or -327 (with respect to the transcription initiation site, 1) conferred positive
      regulation of promoter activity by dexamethasone, cAMP, and phorbol esters.
      Insulin inhibited promoter activity in the presence of any of the three
      stimulatory agents. Stimulation by cAMP or phorbol esters was abolished when the
      region between nt -327 and -235 was deleted. Although this region contains
      potential activating protein-2 and activating protein-1 sites, the sites
      responsible for this regulation have not yet been identified. By contrast,
      stimulation by dexamethasone was retained in deletion constructs whose 5'-end was
      at nt -92, but was abolished by site mutagenesis of either the left or right half
      sites of a potential glucocorticoid response element (GRE) located between nt -91
      and -77. Surprisingly, substitution mutations in an up-stream region, -108 to -99
      (M4), also decreased dexamethasone-stimulated promoter activity despite the
      presence of an intact GRE. We postulate that a positive factor that binds to the
      wild-type M4 region neutralizes factors that inhibit interaction of the
      glucocorticoid receptor with the GRE. The M4 region also is involved in
      inhibition by insulin. Insulin inhibition of dexamethasone-stimulated promoter
      activity was lost after deletion of nt -135 to -92 or mutation of the region
      between nt -108 and -99. This insulin response element is conserved in the human
      IGFBP-1 promoter and is homologous to the insulin response element of the
      phosphoenolpyruvate carboxykinase gene, which also is rapidly inhibited by
      insulin in H4-II-E cells. The rat IGFBP-1 promoter provides a valuable model
      system for studying the multihormonal regulation of transcription.

PMID- 7523865
TI  - SV40 large tumor antigen associated synthetic peptides define native antigenic
      determinants and induce protective tumor immunity in mice.
AB  - Synthetic peptides were utilized to define antigenic determinants on simian virus
      40 (SV40) large tumor antigen (T-ag). Six synthetic peptides representing
      predicted B-cell epitopes on SV40 T-ag were used to immunize mice to compare the
      humoral immune responses and ascertain the ability of the peptide preparations to
      induce protective tumor immunity in vivo. Anti-peptide antibodies from BALB/c and
      C57BL/6 mice were examined for reactivity with SV40 T-ag by various immunologic
      assays. Antibodies from both strains to four of the peptides recognized
      recombinant SV40 T-ag by ELISA. However, T-ag recognition by anti-peptide
      antibodies differed when assessed by Western blot. Antibodies induced by the same
      four peptides in BALB/c mice recognized T-ag, whereas only three of the sex
      peptides induced antibodies in C57BL/6 mice capable of recognizing SV40 T-ag by
      Western blot. Flow cytometric analysis revealed that antibodies to peptides
      corresponding to T-ag amino acid residues 632-652 and 690-708 from BALB/c mice
      were able to recognize the surface of SV40 transformed cells, whereas five of the
      six peptides induced surface reactive antibodies in C57BL/6 mice. More important,
      peptides 632-652 and 690-708 elicited a protective immune response in BALB/c mice
      subsequently challenged with a lethal dose of syngeneic SV40 transformed cells.
      However, this tumor immunity was incomplete as only 50% of the mice survived the
      tumor challenge. These data indicate that antibodies induced by synthetic
      peptides corresponding to predicted B-cell epitopes on SV40 T-ag are capable of
      recognizing native and denatured determinants on T-ag. Furthermore, immune
      responses elicited by selected peptides partially protected BALB/c mice from a
      lethal tumor challenge.

PMID- 7523867
TI  - Polymorphism in the upstream regulatory region and level of expression of HLA-DRB
      genes.

PMID- 7523868
TI  - Epitope complementarity and idiotypic interactions: a study of idiotypic-like
      interactions between anti-cytidine and anti-guanosine A/J mouse monoclonal
      antibodies. III. Immunochemical and structural analysis of a third party
      antibody: an anti-idiotypic antibody directed against an anti-guanosine antibody.

PMID- 7523866
TI  - The receptor with high affinity for IgE on rat mast cells is a functional
      receptor for rat IgG2a.
AB  - Rat mast cells express high-affinity receptors for IgE (Fc epsilon RI) and low
      affinity receptors for IgG (Fc gamma R). In this study, the capacity of IgG to
      activate the rat basophilic leukemia (RBL-2H3) and rat peritoneal mast cells was
      investigated. Immune complexes formed with purified rat IgG and antigen as well
      as chemically cross-linked rat IgG induced histamine release from RBL-2H3 cells.
      This stimulation was inhibited by pre-incubation of the cells with saturating
      concentrations of monomeric IgE. With chemically cross-linked rat IgG of each
      subclass, only IgG2a stimulated histamine release from RBL-2H3 cells and this
      release was also inhibited by prior saturation of the Fc epsilon RI with
      monomeric IgE. Identical results were obtained with rat peritoneal mast cells. In
      binding experiments, IgE and cross-linked rat IgG2a bound to rat Fc epsilon RI
      transfected into CHO cells. Monomeric rat IgG2a, cross-linked rat IgG1, IgG2b,
      IgG2c and rabbit IgG did not bind to Fc epsilon RI. Stimulation of RBL-2H3 cells
      with aggregated IgG2a induced phosphorylation of tyrosines in the beta and gamma
      subunits of the Fc epsilon RI. Thus, although RBL-2H3 and rat peritoneal mast
      cells have Fc gamma R, the IgG-mediated stimulation of these cells for histamine
      release was by the Fc epsilon RI. Altogether, these data demonstrate that the rat
      Fc epsilon RI is a functional receptor with low affinity for rat IgG2a.

PMID- 7523869
TI  - Analysis of B-cell epitopes in the N-terminal region of Chi t I component III
      using monoclonal antibodies.
AB  - The hemoglobins of the midge Chironomus thummi thummi (Chi t I) are known to
      cause immediate-type hypersensitivity reactions in humans. Further knowledge of
      the antigenic sites of such allergens will provide new therapeutic approaches.
      The aim of our study was to identify and characterize linear B-cell epitopes of
      the hemoglobin component III of Chi t I (136 amino acid residues). Using the
      antigenic index algorithm of Jameson and Wolf (Jameson and Wolf (1988) Comput.
      Appl. Biosci. 4, 181-186), three linear binding sequences of this allergen
      molecule were predicted. Two mouse monoclonal antibodies (mAbs 3 and 6) raised
      against purified Chi t I component III were investigated by ELISA for their
      binding to nine synthetic peptides 19-21 residues in length, covering nearly the
      whole sequence of component III. MAb 6 recognized only one peptide (11-30) while
      mAb 3 bound to both N-terminal peptides (1-19 and 11-30), suggesting that the
      antibody binding site is located in the overlapping region. This assumption could
      be confirmed in ELISA with solid phase-bound recombinant peptides (RP) as well as
      in inhibition studies with free tryptic peptides indicating that identification
      of these linear B-cell epitopes is neither influenced by the method of peptide
      production nor by the kind of used immunoassay. To define the essential amino
      acid residues we investigated mAbs with solid phase-bound overlapping octamers.
      In the case of mAb 3, amino acids experimentally identified as essential for
      antibody binding (aa 13-17) are identical with those residues predicted as a B
      cell epitope with the antigenic index of Jameson and Wolf.

PMID- 7523871
TI  - Competitive titration for probing low-abundance ion channel mRNA molecules in
      normal and regionally-ischaemic heart tissue.
AB  - We have measured the expression levels of a range of distinct ion channel genes
      in the apex/ventricle region and sino-atrial node (SAN) sub-regions of heart
      under conditions in which conventional Northern hybridization or ribonuclease
      protection methods were too insensitive or non-quantitative. The abundance of six
      potassium channel mRNAs was determined in relation to a single synthetic
      competitor RNA template which was co-reverse transcribed and PCR-amplified. By
      these methods we have shown that coronary artery ligation procedures which induce
      anoxia and ischaemic scarring in the apical region reduce amplifiable message
      abundance in a time-dependent, but non-specific manner. There was no evidence for
      any selective reduction of individual mRNA levels during this process. Despite a
      high reproducibility of titration endpoints, competitive RNA template
      amplification assays did not provide a simple marker for ischaemic damage, since
      it was not possible to control for tissue sample heterogeneity. We have also
      applied these competitive nucleic acid titration techniques to demonstrate
      expression of cAMP- and cGMP-gated ion channel sequences in small pieces of
      tissue derived from the SAN sub-region of rabbit heart. Although the ion channels
      encoded by these sequences are obligately coupled to intracellular signalling
      agonists commonly found in cardiac cells, they have not been described in
      functional terms within SAN or any other cardiac subregion. For rapid
      determination of cDNA molecular numbers, we have devised single-gene, DNA
      template controls to measure absolute abundance of a cAMP-gated cDNA derived from
      heart tissue. Competitive titration procedures therefore provide an important
      technique for probing gene induction and/or repression accompanying
      pharmacological or surgical interventions, or in progression of disease states.
      For rare cDNAs, they can estimate the representativeness of a given preparation
      prior to library construction, screening and retrieval of clones, while
      eliminating 'false positive' or 'false negative' signals.

PMID- 7523873
TI  - Are rogue cells an indicator of cancer risk due to the action of bacterial
      restriction endonucleases?
AB  - Cytogenetic surveys in normal individuals have occasionally shown the occurrence
      of cells with multiple chromosome-type aberrations in some of the subjects. These
      cells, which are rare, have been termed as rogue cells. Rogue cells, which have
      been observed worldwide, have a mysterious nature. It has been suggested that
      they may give rise to cancer. Various mechanisms have been considered for the
      causation of the rouge-cell phenomenon in the past but none of them appears to be
      fully justified. In this paper we propose their occurrence due to the action of
      bacterial restriction endonucleases.

PMID- 7523872
TI  - Increased initial levels of chromosome damage and heterogeneous chromosome repair
      in ataxia telangiectasia heterozygote cells.
AB  - Individuals heterozygous for ataxia telangiectasia (AT) appear clinically normal
      but have a 2-3-fold overall excess risk of cancer. Various approaches have been
      used to identify AT heterozygotes, however, the results are ambiguous. We
      recently reported that AT homozygotes exhibit more initial chromosome damage
      after irradiation than normal cells despite identical levels of DNA double strand
      breaks (DSBs) as well as a reduced fast repair component at both the DNA and
      chromosome levels. To determine whether AT heterozygotes exhibit the AT or normal
      cellular phenotype, we compared four AT heterozygote lymphoblastoid cell lines
      with normal control and AT homozygote lymphoblastoid cells with regard to cell
      survival, initial levels of damage, and repair at the DNA and chromosome levels
      after gamma-irradiation in G1, S, and G2 phase (estimated by neutral DNA filter
      elution and premature chromosome condensation). There was no significant
      difference in survival, induction and repair of DNA DSBs, or chromosome repair
      between AT heterozygote and normal cells. In contrast, all four AT heterozygote
      cell lines showed increased levels of chromosome damage; G1 phase cells showed
      intermediate levels and G2 phase cells showed levels equivalent to the AT
      homozygote phenotype. These results suggest that premature chromosome
      condensation may be useful for detecting AT heterozygotes.

PMID- 7523870
TI  - Antigenic peptide binding to MHC class II molecules at increased peptide
      concentrations.
AB  - Affinity-purified major histocompatibility complex (MHC) class II molecules are
      known to bind antigenic peptides in vitro. The percentage of MHC class II
      molecules occupied with such peptides is usually very low and varies
      significantly depending upon the sequence and size of a given antigenic peptide.
      The present study describes a method by which complete saturation of affinity
      purified MHC class II with antigenic peptide can be achieved by simply incubating
      purified MHC class II molecules at neutral pH in the presence of several 100-fold
      molar excess of antigenic peptide. Complexes of human HLA-DR2 and a peptide
      analog from human myelin basic protein MBP (83-102)Y83 were selected for this
      study. The on-rate kinetic results showed saturation of MHC class II occupancy at
      300-500-fold molar excess peptide concentrations. The specificity of the MBP (83
      102)Y83 peptide binding to HLA-DR2 at higher peptide concentration was
      demonstrated by incubating an equivalent amount of another epitope from myelin
      basic protein [MBP (1-14) peptide] as well as by competitive binding assays. The
      quantitation of bound peptide was carried out using biotinylated-MBP (83-102)Y83
      peptide which showed 100-125% occupancy of HLA-DR2 with a recovery of 100%. The
      presence of a single peptide entity in purified complexes was confirmed by
      reverse-phase narrowbore HPLC analysis of the acid extracted supernatant and by
      mass spectrometry analysis. Two-dimensional gel electrophoresis (IEF/SDS) of
      purified HLA-DR2 and DR2.MBP (83-102)Y83 complexes showed the absence of various
      endogenous polypeptides in 100% loaded complexes. These results demonstrate that
      higher peptide concentrations can be useful in generating MHC class II-peptide
      complexes of defined composition. Such complexes of MHC class II occupied with a
      single peptide may have significant clinical relevance for antigen-specific
      therapy of various autoimmune diseases and may provide better understanding of
      MHC-peptide-TCR interactions.

PMID- 7523874
TI  - Suppressing effects of human fetal cell extract on micronuclei induced by
      cyclophosphamide in mice.
AB  - The genotoxicity of human fetal cell extract (HFCE) and its effect on the
      frequency of micronucleated polychromatic erythrocytes (PCE-MNF) in mice induced
      by cyclophosphamide (CP) were studied. Statistically significant differences were
      not found between the control group and each group treated with HFCE (0.3, 3, 30
      mg/kg bw). CP (200 mg/kg bw) induced a marked increase in MNF (P < 0.01).
      Administered together with CP, HFCE suppressed the increase of MNF induced by CP.
      The reduction effect is dependent on the dose of HFCE. At doses of 3 and 30 mg/kg
      bw HFCE, MNF decreased markedly (P < 0.05 and < 0.01, respectively). It showed
      that HFCE did not induce micronucleus formation, while it could suppress the
      micronucleus formation induced by CP in mice. The results suggested that HFCE
      might be antimutagenic and have potential value in clinical application.

PMID- 7523875
TI  - Induction of mutation, sister-chromatid exchanges, and chromosome aberrations by
      3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in Chinese hamster ovary
      cells.
AB  - The strong bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone
      (MX) was tested for the induction of mutation at the Na/K ATPase locus to ouabain
      resistance (OuaR), sister-chromatid exchanges (SCEs), and chromosome aberrations
      (CAs) in Chinese hamster ovary (CHO) cells without metabolic activation. MX
      increased the frequency of OuaR mutants in CHO cells when the cells were treated
      with it in PBS (effective dose range 2-3 micrograms/ml) or in medium (McCoy's 5A)
      without serum (effective dose range 20-30 micrograms/ml). MX also induced SCEs in
      CHO cells, at 0.19-1.5 microgram/ml, exposure in PBS; at 6-24 micrograms/ml,
      exposure in medium; and at 3-24 micrograms/ml, exposure in medium plus 2.5% fetal
      calf serum. The maximum induction of SCEs was about 1.5-2.5-fold compared with
      control level, irrespective of exposure conditions (PBS, medium or medium plus
      serum). The most pronounced genotoxic effect of MX was observed in CAs (100%
      aberrant cells at the dose level of 4 micrograms/ml, exposure in PBS) which were
      mainly of the chromatid type. In general, MX was more toxic to CHO cells treated
      in PBS compared with exposure in medium or medium plus 2.5% serum.

PMID- 7523876
TI  - Hereditary non-polyposis colorectal cancer--morphologies, genes and mutations.
AB  - Mutations in a human homologue of the yeast DNA mismatch repair gene MSH2
      (equivalent to bacterial MutS) cause the condition hereditary non-polyposis
      colorectal cancer (HNPCC). Cancers in HNPCC originate within benign neoplastic
      polyps termed adenomas. Adenomas are clonal and each may serve as a marker of a
      single initiating mutation. The progression of adenomas is marked by increasing
      size, dysplasia and villosity. These characteristics can be taken as the
      morphological counterparts of the stepwise accumulation of mutations implicating
      oncogenes and tumour suppressor genes. The aim of this study was to link the
      morphogenesis of hereditary colorectal cancer with recent insights into the role
      of DNA mismatch repair genes. The frequency and anatomical distribution of
      adenomas in at-risk members of HNPCC families was the same as in an autopsy
      population. This suggests that the HNPCC gene does not initiate the process of
      neoplastic transformation. On the other hand, adenomas in at-risk members of
      HNPCC families were more likely to show villosity (p < 0.001), high grade
      dysplasia (p = 0.002) and probably increased size (p = 0.15). These findings are
      consistent with the observation that the HNPCC gene causes DNA replication errors
      to develop and accumulate within neoplastic but not normal tissues. The effect of
      the HNPCC gene is to accelerate the progression of adenoma to carcinoma, but not
      to initiate adenoma development.

PMID- 7523878
TI  - Evaluation of benomyl and carbendazim in the in vivo aneuploidy/micronucleus
      assay in BDF1 mouse bone marrow.
AB  - Benomyl and its active metabolite carbendazim were investigated in BDF1 mouse
      bone marrow to establish whether micronuclei induced by these fungicides are
      caused by clastogenic or aneugenic events. Micronuclei were evaluated for
      kinetochores using immunofluorescent antikinetochore antibodies. Kinetochore
      positive (K+) micronuclei are likely to arise from chromosome loss since they
      presumably contain intact kinetochores and are indicative of aneuploidy.
      Conversely, kinetochore negative (K-) micronuclei are mostly likely to contain
      acentric chromosome fragments arising primarily from clastogenic damage. Benomyl
      and carbendazim were administered as single oral doses of 0.3, 8.6 or 17.2
      mmol/kg (for benomyl, equivalent to 100, 2500 or 5000 mg/kg; for carbendazim,
      equivalent to 66, 1646 or 3293 mg/kg). Both compounds were positive in the
      micronucleus test at doses of 8.6 and 17.2 mmol/kg, and an average of 82%
      (benomyl) and 87% (carbendazim) of the total micronucleated polychromatic
      erythrocytes were K+. No effects were seen with either fungicide at 0.3 mmol/kg.
      These results are analogous to findings with known aneugens such as vincristine
      but are in contrast to results with classical clastogens such as
      cyclophosphamide. Thus, benomyl and carbendazim induce micronuclei in mouse bone
      marrow cells primarily through an aneugenic mechanism.

PMID- 7523877
TI  - Chromosome aberrations in peripheral lymphocytes from occupants of houses with
      elevated indoor radon concentrations.
AB  - Chromosome analyses were performed in blood lymphocytes of 25 subjects
      continuously living in houses with indoor radon (222Rn) concentrations exceeding
      4-60-fold the German average of 50 Bqm-3. The mean frequency of cells containing
      dicentrics + ring chromosomes (1.3 +/- 0.3/1000 cells) and the incidence of
      dicentrics + ring chromosomes per cell (1.5 +/- 0.4 x 10(-3)) were significantly
      increased compared to the control levels (0.54 +/- 0.11 x 10(-3) for both
      endpoints). Taking into account the individual radiation history over the last 10
      years prior to blood sampling and the life time of peripheral lymphocytes,
      weighted cumulative radon exposures at the time of blood sampling between 700 and
      6300 Bqm-3a were derived. Although individual exposures could not be inferred
      from the aberration rates, a tendency for an exposure-effect relationship became
      apparent for two groups of subjects with a mean weighted cumulative radon
      exposure above and below 1800 Bqm-3a.

PMID- 7523881
TI  - Cytogenetic analysis of lymphocytes from fiberglass-reinforced plastics workers
      occupationally exposed to styrene.
AB  - In this study a group of 52 workers employed in a plant manufacturing fiberglass
      reinforced plastic (FRP) pipes and cisterns, and therefore daily exposed to
      styrene, were monitored. As a control group 24 non-exposed workers from another
      factory producing and repairing pallets volunteered to participate. The airborne
      styrene during the monitoring ranged from 2.2 to 110.1 mg/m3. As a metabolic
      marker for styrene exposure mandelic acid was measured in the urine and ranged
      from 11 to 649 mg/g creatinine. From 43 exposed and 15 control workers sister
      chromatid exchanges (SCE) and high frequency cell (HFC) data and from 49 exposed
      and 23 control workers micronucleus (MN) data from peripheral lymphocytes are
      reported. Although the two groups of workers could clearly be distinguished on
      the basis of the airborne styrene concentrations and urinary mandelic acid
      concentrations no differences in any of the cytogenetic markers were found.
      Correlations between the cytogenetic data and the level of airborne styrene
      concentrations or urinary mandelic acid levels could also not be demonstrated.
      Otherwise, smoking increased the SCE frequency. Grouping the workers according to
      smoking habits showed a statistically significant difference in SCE. Moreover,
      levels of urinary thiocyanate (SCN), which can be used as a metabolic marker for
      smoking, showed a significant positive correlation with the number of SCE. This
      indicates that SCE is a sensitive biomarker and might still be useful in
      biomonitoring. However, only chronic exposures over a long period would probably
      be detectable. In this study, where exposure was rather low and the number of
      working years was small (mean of 2.9 years), cytogenetic effects are probably too
      low or rare to be detectable with any assay.

PMID- 7523879
TI  - Forward-mutation tests on the antitumor agent ICR-170 in Neurospora crassa
      demonstrate that it induces gene/point mutations in the ad-3 region and an
      exceptionally high frequency of multiple-locus ad-3 mutations with closely linked
      sites of recessive lethal damage.
AB  - The mutagenicity of the antitumor agent ICR-170 (2-methoxy-6-chloro-9-[(ethyl-2
      chloroethyl)amino propylamino] acridine dihydrochloride) in the adenine-3 (ad-3)
      region was studied with a two-component heterokaryon (H-12) of Neurospora crassa.
      The objective was to characterize the genetic damage produced by this acridine
      nitrogen mustard derivative to determine in a lower eukaryotic organism the basis
      for its potent activity against ascites tumors in mice. As in higher eukaryotes,
      specific-locus mutations in the ad-3 region of strain H-12 result from gene/point
      mutations, multiple-locus mutations, and multilocus deletion mutations at the
      closely linked ad-3A and ad-3B loci. Six different treatments of conidial
      suspensions of H-12 with ICR-170 were used to obtain dose-response curves for
      inactivation of conidia as well as the overall induction of ad-3 forward
      mutations using a direct method based on pigment accumulation rather than a
      requirement for adenine. These experiments demonstrated that: (1) the slope of
      the dose-response curve for ICR-170-induced specific-locus mutations in the ad-3
      region was 1.97 +/- 0.02, and (2) ICR-170 is a potent mutagen (maximum forward
      mutation frequency between 1000 and 10,000 ad-3 mutations per 10(6) survivors)
      for the induction of specific-locus mutations in the ad-3 region. Both
      biochemical and classical genetic tests were used to characterize the ICR-170
      induced ad-3 mutations from each of the six treatments to distinguish the
      different genotypic classes and subclasses. The overall data base demonstrates
      that ICR-170-induced ad-3 mutations result exclusively from gene/point mutations
      at the ad-3A and ad-3B loci and not multilocus deletion mutations. In addition,
      the frequency of multiple-locus ad-3 mutations resulting from gene/point
      mutations at the ad-3A and ad-3B loci with a separate site of recessive lethal
      damage elsewhere in the genome increases as a function of dose. However, an
      exceptionally high frequency of multiple-locus ad-3 mutations consisting of
      gene/point mutations at the ad-3A and ad-3B loci with a separate site of closely
      linked recessive lethal damage was found at all doses. Comparison of the dose
      response curves for the major classes and subclasses of ICR-170-induced ad-3
      mutations demonstrates that the gene/point ad-3 mutations and multiple-locus ad-3
      mutations with a separate site of recessive lethal damage elsewhere in the genome
      have different induction kinetics.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523880
TI  - Radioadaptive response in primary mouse spermatocytes revealed by analysis of
      synaptonemal complexes.
AB  - This study was aimed at estimating the damage to the synaptonemal complex (SC) of
      male mice caused by radiation exposure at the ultimate pre-meiotic interphase.
      Four experimental groups were formed: group 1 was an untreated control, group 2
      received a low dose (50 mGy) of radiation, group 3 a high dose (4 Gy) of
      radiation, group 4 was first treated with a low dose (50 mGy) and 4 h later with
      a high dose (4 Gy). Mice were killed 4 days after the treatment. Early pachytene
      cells were selected for the electron microscopic analysis of SCs. These cells
      were supposed to be at pre-meiotic interphase at the time of irradiation.
      Treatment with a low dose of radiation did not produce any substantial increase
      in the frequency of SC aberrations, while exposure to the high dose resulted in
      various types of damage. Group 4 demonstrated significantly lower frequencies of
      axial breaks/fragments and multiaxial configurations than group 3. At the same
      time, these two groups did not differ in the frequencies of inter- and
      intrachromosomal exchanges such as translocations, inversions, and deletions. We
      suppose that the number of breaks produced by a high dose of radiation was the
      same in the both groups. However, a proportion of the breaks that remained
      unrepaired until pachytene and were expressed as gaps, fragments, and multiaxial
      configurations was reduced by pretreatment with the low dose of radiation.

PMID- 7523882
TI  - Induction of micronuclei and granular chromatin condensation in human skin
      fibroblasts influenced by cisplatin (cis-DDP) in vitro.
AB  - Chromosomal damage was evaluated by quantification of micronuclei (MN) in two
      cell lines of human skin fibroblasts treated with different concentrations of
      cisplatin (ranging from 2 to 80 mumol/l) over the following time intervals: 2, 24
      and 48 h. The formation of micronuclei was dependent upon the concentration of
      cis-DDP as well as on the duration of exposure. The dose-response curve for
      micronuclei in treated cells revealed a bell shape with the maximum at 12.5
      mumol/l cis-DDP. The results were compared with another toxicological phenomenon,
      granular condensation of nuclear chromatin. This change, which was closely
      related to apoptosis in the cells exposed to cis-DDP, occurred at 5 mumol/l. The
      degree of condensation of nuclear chromatin depended on the concentration of cis
      DDP. In contrast to the observations for micronuclei, the dose-effect
      relationship was linear up to the highest tested concentration (80 mumol/l). This
      change was primarily due to the duration of cis-DDP treatment. Our results showed
      the comparison between micronucleus formation and granular condensation of
      nuclear chromatin, as two morphological manifestations of cisplatin-induced DNA
      damage.

PMID- 7523883
TI  - Induction of mutations at the hypoxanthine phosphoribosyl transferase (HPRT)
      locus in AHH-1 human lymphoblastoid cells.
AB  - Cells from the human lymphoblastoid cell line, AHH-1, were exposed to two direct
      acting mutagens, ethyl methanesulfonate (EMS) and ethyl nitrosourea (ENU), and to
      three carcinogens that require metabolic activation to an electrophile,
      benzo[a]pyrene (B(a)P), 6-aminochrysene (6-AC), and 6-nitrochrysene (6-NC);
      mutation induction at the HPRT locus was quantified by resistance to 6
      thioguanine (6-TGr). Exposure of AHH-1 cells to either EMS or ENU resulted in a
      concentration-dependent increase in mutant frequency at the HPRT locus. When AHH
      1 cells were exposed to B(a)P, the increase in mutant frequency at the HPRT locus
      was marginally significant linearly and significant quadratically. The 32P
      postlabeling assay revealed the formation of DNA adducts derived from (+/-)anti
      benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide which may account for the
      increase in 6-TGr clones. Although DNA adducts could be detected by the 32P
      postlabeling assay in both 6-NC- and 6-AC-treated AHH-1 cells, exposure to 6-AC
      or 6-NC did not result in a concentration-dependent increase in mutant frequency
      at the HPRT locus. Our results are consistent with the results of previous
      studies which indicate that EMS and ENU are effective inducers of 6-TGr clones as
      is B9(a)P when activated to an electrophile. In 6-NC- and 6-AC-exposed cells, low
      levels of N-hydroxy-6-aminochrysene-derived adducts were detected in only 6-NC
      exposed cells. No 6-aminochrysene-1,2-dihydrodiol-derived adducts were detected
      following 6-NC or 6-AC exposure. Minimal metabolic activation of 6-NC or 6-AC by
      AHH-1 cells may account for the lack of a positive mutagenic response for either
      6-AC or 6-NC.

PMID- 7523884
TI  - Influence of PHA stimulation on the cytotoxicity and mutagenicity of X-rays and
      ethylnitrosourea in human peripheral blood T-lymphocytes.
AB  - We investigated the effects of mitogenic stimulation on the cytotoxicity and
      mutagenicity of X-rays and ethylnitrosourea (ENU) in human peripheral blood
      lymphocytes using a cloning technique. Resistance to 6-thioguanine (TG) served as
      the genetic marker. Day 0 (unstimulated) lymphocytes were about two times more
      radiosensitive than day 3 (stimulated) lymphocytes to the cytotoxicity when
      compared for the D0 value (0.72 Gy vs. 1.54 Gy), and about five times more
      radiosensitive to its mutagenicity when compared for the frequency of TG
      resistant cells following exposure to 4 Gy of X-rays (25.5 x 10(-6) vs. 126.0 x
      10(-6). On the other hand, day 3 (stimulated) lymphocytes were about three times
      more sensitive to ENU with a D37 value of 1.03 mM compared with 2.82 mM for day 0
      (unstimulated) lymphocytes, but as sensitive as day 0 lymphocytes to its
      mutagenic effect. These results indicate that the sensitivity of lymphocytes for
      cytotoxicity and mutagenicity is modified by mitogen stimulation, when
      lymphocytes are exposed to carcinogens or mutagens in vitro.

PMID- 7523885
TI  - Mitotic metaphase cells from different cell lines cause different levels of
      expression of the alpha-form of interphase chromosome breaks in irradiated CHO
      cells.
AB  - We previously showed that HeLa mitotic metaphase cells, when used as inducers of
      premature chromosome condensation (PCC), uncover two times more chromosome breaks
      in irradiated interphase cells than CHO mitotic metaphase cells, and have at the
      same time a 2.5-fold higher mitosis promoting factor (MPF) activity. In a
      different set of experiments, we provided evidence that ionizing radiation
      induces two forms of interphase chromosome breaks, the alpha- and the beta-form,
      that can be discriminated from each other based on their kinetics of rejoining,
      their sensitivities to postirradiation treatments, and the genetic requirements
      of their repair. Here we demonstrate that HeLa mitotic metaphase cells increase
      the radiation yield of interphase chromosome breaks by specifically uncovering
      interphase chromosome damage of the alpha-form. Using xrs-5 cells that
      constitutively express chromosome breaks of the beta-form, we also show that the
      choice of metaphase cells does not affect the expression of the beta-form of
      interphase chromosome breaks. These observations add yet another qualitative and
      quantitative difference between alpha- and beta-forms of interphase chromosome
      breaks, and suggest that separation of radiation damage into two components will
      be helpful in the description of radiation action in living cells. The finding
      that different types of mitotic inducer cells give widely different yields of
      interphase chromosome breaks indicates that a quantitative comparison of the
      results obtained by different investigators should be made with caution and
      should consider the type of mitotic cells used.

PMID- 7523886
TI  - Possible occurrence of P450 related to P450 HFLb in extrahepatic tissues of human
      fetuses and its contribution to metabolic activation of promutagens.
AB  - P450 HFLb purified from human fetal livers has been shown to be constitutively
      expressed in fetal livers. In the present study, the occurrence of proteins
      immunochemically related to P450 HFLb in extrahepatic tissues of human fetuses
      and their contribution to mutagenic activation of promutagens were investigated.
      The mutagenic activation of aflatoxin B1 (AFB1), 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and
      benzo[a]pyrene were observed in human fetal extrahepatic tissues, including
      adrenal glands, kidneys and lungs, at varying rates. Immunoblot analysis of
      homogenates of extrahepatic tissues with antibodies to P450 HFLb revealed the
      occurrence of proteins immunochemically related to P450 HFLb in adrenal glands,
      kidneys and lungs. Immuno-inhibition studies suggested that in fetal adrenal
      gland and kidney, the proteins cross-reactive with antibodies to P450 HFLb were
      capable of activating IQ and MeIQ to mutagens.

PMID- 7523888
TI  - Xeroderma pigmentosum group E binding factor recognizes a broad spectrum of DNA
      damage.
AB  - Xeroderma pigmentosum complementation group E binding factor (XPE-BF) is a
      damaged DNA binding protein that is deficient in a subset of patients from
      complementation group E of xeroderma pigmentosum. The protein recognizes various
      forms of DNA damage including some cyclobutane pyrimidine dimers, 6-4
      photoproducts, cis-diamminedichloroplatinum(II) adducts, and single-stranded DNA.
      We now show that it also recognizes damage induced by nitrogen mustard; N-methyl
      N'-nitro-N-nitrosoguanidine, and depurination, but has no detectable affinity for
      DNA adducts generated by trans-diamminedichloroplatinum(II), 4-nitroquinoline-N
      oxide, 8-methoxypsoralen, or enzymatically methylated cytosine and adenine. The
      failure to recognize 4-nitroquinoline-N-oxide and 8-methoxypsoralen adducts is
      consistent with previous reports that XPE cells carry out wild-type levels of
      repair synthesis after DNA damage by those drugs. These results demonstrate that
      XPE-BF is a versatile damage recognition protein, but suggest that other proteins
      must contribute to the recognition of DNA lesions for the human excision repair
      pathway.

PMID- 7523887
TI  - Role of active oxygen species in DNA damage by pentachlorophenol metabolites.
AB  - Pentachlorophenol (PCP) has been shown to be carcinogenic for mice, although it
      does not seem to be mutagenic in bacterial test systems. In this study, the
      mechanism of DNA damage by PCP metabolites in the presence of metals was
      investigated with a DNA sequencing technique using 32P-labeled DNA fragments and
      with an electrochemical detector coupled to an HPLC. The metabolite
      tetrachlorohydroquinone (TCHQ) caused DNA damage in the presence of Cu(II) but
      not in the presence of either Mn(II) or Fe(III). TCHQ plus Cu(II) frequently
      induced piperidine-labile sites at thymine residues and guanine residues. The
      most preferred sites were the thymine residues of the 5'-GTC-3' sequence. TCHQ
      increased 8-oxo-7,8-dihydro-2'-deoxyguanosine in calf thymus DNA in the presence
      of Cu(II). Typical OH scavengers showed no inhibitory effects on TCHQ- plus
      Cu(II)-induced DNA damage. Bathocuproine and catalase inhibited DNA damage,
      suggesting that Cu(I) and H2O2 have important roles in the production of active
      species causing DNA damage. Tetrachloro-p-benzoquinone (TCBQ) alone did not
      induce DNA damage in the presence of Cu(II), but addition of NADH induced DNA
      cleavage even in the absence of NADH-FMN oxidoreductase. UV-visible and ESR
      spectroscopies have demonstrated that TCHQ is rapidly autoxidized into
      semiquinone even in the absence of metal ions, indicating that the semiquinone
      radical itself is not the main active species inducing DNA damage. These results
      suggest that the semiquinone radical produced by the autoxidation of TCHQ and/or
      the reduction of TCBQ by NADH reacts with dioxygen to form superoxide and
      subsequently H2O2, which is activated by transition metals to cause DNA damage.

PMID- 7523889
TI  - Environmental monitoring for genotoxicity with plant systems. An introduction and
      study design.
AB  - Under the sponsorship of the International Programme on Chemical Safety (IPCS),
      17 laboratories from diverse regions of the world participated in evaluating the
      utility of four plant bioassays for detecting genetic hazards of environmental
      chemicals. The bioassays included in this collaborative study were: Arabidopsis
      thaliana embryo and chlorophyll assay and Tradescantia stamen hair assay,
      Tradescantia paludosa micronucleus assay and Vicia faba root tip assay. Four to
      six laboratories participated in the performance of each of the bioassays. All
      laboratories participating in a particular bioassay were supplied with uniform
      plant material as well as standardized protocol. Five direct acting water soluble
      test chemicals, i.e. maleic hydrazide, methyl nitrosourea, ethyl
      methanesulfonate, sodium azide and azidoglycerol, were selected for this study.
      The study was designed to be completed in three phases. Ethyl methanesulfonate
      was used as a positive control and has already been reported earlier (Sandhu et
      al., 1991). The data from the remaining four chemicals used for the evaluation of
      four plant test systems in the first phase of the collaborative study are
      reported in this issue.

PMID- 7523890
TI  - The present status of higher plant bioassays for the detection of environmental
      mutagens.
AB  - Higher plants provide valuable genetic assay systems for screening and monitoring
      environmental pollutants. They are now recognized as excellent indicators of
      cytogenetic and mutagenic effects of environmental chemicals and are applicable
      for the detection of environmental mutagens both indoor and outdoor. Comparisons
      between plant and nonplant genetic assay systems indicate that higher plant
      genetic assays have a high sensitivity (i.e. few false negatives). Two assays
      which are considered ideal for in situ monitoring and testing of airborne and
      aqueous mutagenic agents are the Tradescantia stamen hair assay for mutations and
      the Tradescantia micronucleus assay for chromosome aberrations. Both assays can
      be used for in vivo and in vitro testing. Other higher plant genotoxicity assays
      which have a large number of genetic markers and/or data base and are also highly
      suitable for testing for genotoxic agents include Arabidopsis thaliana, Allium
      cepa, Hordeum vulgare, Vicia faba, and Zea mays. Since higher plant systems are
      now recognized as excellent indicators of the cytotoxic, cytogenetic, and
      mutagenic effects of environmental chemicals and have unique advantages for in
      situ monitoring and screening it is recommended that higher plant systems be
      accepted by regulatory authorities as an alternative first-tier assay system for
      the detection of possible genetic damage resulting from pollution or the use of
      environmental chemicals. The results from higher plant genetic assays could make
      a significant contribution in protecting the public from agents that can cause
      mutation and cancer. The advantages possessed by higher plant genetic assays,
      which are inexpensive and easy to handle, make them ideal for use by scientists
      in developing countries.

PMID- 7523891
TI  - Comparative mutagenicity of chemicals selected for test in the International
      Program on Chemical Safety's collaborative study on plant systems for the
      detection of environmental mutagens.
AB  - A review has been made for the four compounds (maleic hydrazide, methyl
      nitrosourea, sodium azide, azidoglycerol) tested in the International Program on
      Chemical Safety's collaborative study on plant systems. Maleic hydrazide (MH) is
      a weak cytotoxic/mutagenic chemical in mammalian tissues and is classified as a
      class 4 chemical. In contrast, with few exceptions such as Arabidopsis, MH is a
      potent mutagen/clastogen in plant systems. The difference in its response between
      plant and animal tissue is likely due to differences in the way MH is
      metabolized. MH appears to be noncarcinogenic and has been given a negative
      NCI/NTP carcinogen rating. Methyl nitrosourea (MNU) is a toxic, mutagenic,
      radiomimetic, carcinogenic, and teratogenic chemical. It has been shown to be a
      mutagen in bacteria, fungi, Drosophila, higher plants, and animal cells both in
      vitro and in vivo. MNU is a clastogen in both animal and human cell cultures,
      plant root tips and cell cultures inducing both chromosome and chromatid
      aberrations as well as sister-chromatid exchanges. Carcinogenicity has been
      confirmed in numerous studies and involves the nervous system, intestine, kidney,
      stomach, bladder and uterus, in the rat, mouse, and hamster. MNU produces stage
      specific teratogenic effects and also interferes with embryonic development. The
      experimental evidence that strongly indicates the mutagenic effects of MNU
      underlines the possible hazard of this compound to human beings. The experimental
      evidence for the stringent handling of this compound is clear. Sodium azide
      (NaN3) is cytotoxic in several animal and plant systems and functions by
      inhibiting protein synthesis and replicative DNA synthesis at low dosages. It is
      mutagenic in bacteria, higher plants and human cells and has been used as a
      positive control in some systems. In general, tests for clastogenicity have been
      negative or weakly positive. No evidence of carcinogenicity has been reported in
      a 2-year study seeking carcinogenic activity in male and female rats. Its
      advantages in comparison to other efficient mutagens are claimed to be a high
      production of gene mutations accompanied by a low frequency of chromosomal
      rearrangements and safer handling because of its nonclastogenic and
      noncarcinogenic action on humans. Azidoglycerol (AG) is a very potent mutagen in
      bacteria, yeast and higher plants including Arabidopsis and Tradescantia;
      however, it only slightly enhances the frequencies of recessive lethals in
      Drosophila. AG is at best a weak clastogen and is without effect in inducing
      chromosomal aberrations and SCEs in human peripheral lymphocytes in vitro. In
      microbial and plant systems, AG is considerably more potent than sodium azide in
      the maximal frequencies of mutation induced. In particular, in Saccharomyces
      cerevisae, AG is 3000-fold more mutagenic than sodium azide. Its carcinogenic and
      teratogenic properties are unknown.

PMID- 7523892
TI  - Tradescantia stamen hair mutation bioassay.
AB  - The Tradescantia stamen hair mutation (Trad-SH) assay (clone 4430) was evaluated
      for its efficiency and reliability as a screen for mutagens in an IPCS
      collaborative study on plant systems. Four coded chemicals, i.e. azidoglycerol
      (AG, 3-azido-1,2-propanediol), N-methyl-N-nitrosourea (MNU), sodium azide (NaN3)
      and maleic hydrazide (MH) were distributed by the Radian Corporation to the five
      laboratories in five different countries for testing mutagenicity. Pink mutations
      were scored between the 7th and 14th day according to a standard protocol. Test
      results from the five individual laboratories were analyzed and compared after
      decoding. One out of the two laboratories that conducted tests on AG demonstrated
      that AG is a mutagen with genetically effective doses ranging from 50 to 100
      micrograms/ml. MH yielded positive responses in all laboratories but no linear
      dose-response pattern was observed. The effective dose range for MH was between 1
      and 45 micrograms/ml. The mutagenicity of MNU was reported by five laboratories
      in the dose range between 10 and 80 micrograms/ml. NaN3, which exhibited a
      relatively high degree of toxicity, elicited a positive mutagenic response in
      three of the five laboratories in which it was tested. As with MNU the effective
      dose for NaN3 ranged between 3 and 80 micrograms/ml. The results from the current
      study substantiate the Trad-SH assay as a reliable system for screening chemicals
      for their potential mutagenic effects. Although the study was carried out
      exclusively under laboratory conditions, a survey of the current literature would
      indicate that the Trad-SH assay could be an effective in situ monitor of gaseous,
      liquid, and radioactive pollutants as well.

PMID- 7523893
TI  - Tradescantia micronucleus bioassay.
AB  - Four coded chemicals, azidoglycerol (AG), N-methyl-N-nitrosourea (MNU), sodium
      azide (NaN3), and maleic hydrazide (MH), were tested with the Tradescantia
      micronucleus (Trad-MCN) bioassay by five independent laboratories from five
      different countries. The purpose of this international collaborative study was to
      evaluate four plant bioassays, of which the Trad-MCN assay was one, for their
      sensitivity, efficiency and reliability. The study was carried out under the
      sponsorship of the International Programme on Chemical Safety. All laboratories
      adhered to a standard Trad-MCN protocol which suggested that three replicate
      tests be conducted with each chemical. The results reported by all laboratories,
      although not equal, showed good agreement among the laboratories. In fact, all
      five laboratories obtained positive results with MH and MNU, while four of the
      five laboratories achieved positive results with NaN3. AG was tested in only
      three laboratories. Two reported negative results, while one reported positive
      results but only at a single high dose. The data from this study suggest that
      under normal conditions, the Trad-MCN bioassay is an efficient and reliable short
      term bioassay for clastogens. It is suitable for the rapid screening of
      chemicals, and also is specially qualified for in situ monitoring of ambient
      pollutants.

PMID- 7523894
TI  - Vicia faba chromosomal aberration assay.
AB  - A collaborative study involving laboratories in six countries was initiated under
      the sponsorship of the International Programme on Chemical Safety (IPCS) to
      determine the sensitivity, efficiency and reliability of the Vicia faba root tip
      meristem chromosomal aberration assay using a standardized protocol. The six
      laboratories that participated in this study were located in the Slovak Republic,
      India, Japan, Poland, Sweden and the USA. All laboratories adhered to a
      standardized protocol for the Vicia faba chromosomal aberration assay. Four coded
      chemicals, azidoglycerol (AG), N-methyl-N-nitrosourea (MNU), sodium azide (NaN3)
      and maleic hydrazide (MH) were tested with the Vicia faba chromosomal aberration
      assay. Of the four chemicals, three (MH, AG and MNU) were found to be clastogenic
      and gave a concentration related response. However, the results of NaN3 were
      equivocal which might be explained by the stability of NaN3. The conclusions from
      this study suggest that the Vicia faba chromosomal aberration bioassay is an
      efficient and reliable short-term bioassay for the rapid screening of chemicals
      for clastogenicity.

PMID- 7523895
TI  - Arabidopsis assay for mutagenicity.
AB  - Four laboratories, two in the Czech Republic (Brno and Prague) and two in the CIS
      (Moscow and Duschanbe), participated in the International Programme on Chemical
      Safety's (IPCS) collaborative study to evaluate the utility of the most commonly
      used plant test systems, including the Arabidopsis thaliana assay, for assessing
      the mutagenic potential of environmental agents. Out of the five compounds
      evaluated in the Arabidopsis assay, three compounds, i.e., ethyl
      methanesulfonate, N-methyl-N-nitrosourea, and azidoglycerol, were reported to be
      mutagenic by all four participating laboratories. Sodium azide (NaN3)
      demonstrated a negative response in all four laboratories, whereas maleic
      hydrazide was reported to be weakly mutagenic by one laboratory and nonmutagenic
      by the other three laboratories.

PMID- 7523898
TI  - Biomarkers and molecular epidemiology in mutation/cancer research.

PMID- 7523896
TI  - Environmental monitoring for genotoxicity with plant systems. Results and
      recommendations.
AB  - In the first phase of a collaborative study by the International Programme on
      Chemical Safety (IPCS), four coded chemicals, i.e. azidoglycerol (AG, 3-azido-1,2
      propanediol), methyl nitrosourea (MNU), sodium azide (NaN3) and maleic hydrazide
      (MH), and ethyl methanesulfonate (EMS) as a positive control were tested in four
      plant bioassays, namely the Arabidopsis embryo and chlorophyll mutation assay,
      the Tradescantia stamen hair assay (Trad-SH assay), the Tradescantia micronucleus
      assay (Trad-MCN), and the Vicia faba root tip assay. Seventeen laboratories from
      diverse regions of the world participated with four to six laboratories each
      using one plant assay. For the Arabidopsis assay, laboratories were in agreement
      with MNU and AG giving positive responses and NaN3 giving a negative response.
      With the exception of one laboratory which reported MH as weakly mutagenic, no
      mutagenic response was reported for MH by the other laboratories. For the Vicia
      faba assay, all laboratories reported a positive response for MNU, AG, and MH,
      whereas two of the six laboratories reported a negative response for NaN3. For
      the Trad-SH assay, MH was reported as giving a positive response and a positive
      response was also observed for MNU with the exception of one laboratory. NaN3,
      which exhibited a relatively high degree of toxicity, elicited a positive
      response in three of the five laboratories. AG was found positive in only one of
      the two laboratories which tested this chemical. For the Trad-MCN assay, MNU and
      MH were reported as positive by all laboratories, while four out of five
      laboratories reported NaN3 to be positive. Only one of three laboratories
      reported AG to be positive. The major sources of variability were identified and
      considered to be in the same range as found in similar studies on other test
      systems. Recommendations were made for minor changes in methodology and for
      initiating the second phase of this study.

PMID- 7523897
TI  - The parallelogram approach in studies of genotoxic effects.
AB  - Over the past two decades mutagenicity tests have been used for the
      identification of potential human mutagens and have had an ancillary role, as
      supportive evidence in the assessment of human carcinogens. The demonstration of
      human germinal mutagens has been beyond the main scope of short-term testing
      strategies. However, just as mutagenicity tests have been useful in detecting
      potential carcinogens so should carcinogenicity tests assist the identification
      of presumptive germ cell mutagens. Cancer is an easily observable phenotype of
      mutation for genotoxic carcinogens and multi-site carcinogens or gonadal
      carcinogens logically could be germ cell mutagens. Thus carcinogenicity and
      mutagenicity data for a given genotoxic chemical should be considered together in
      the identification of putative germinal mutagens. Clearly, most classified human
      carcinogens are genotoxic thus helping to build the case for human germ cell
      mutagenicity. This paper describes the issues involved in such thinking and
      suggests an enhanced parallelogram approach incorporating the cancer endpoint.
      The enhanced parallelogram is explored using 1,3-butadiene and ethylene oxide as
      examples. The obvious lack of data for extrapolations using the parallelogram
      method suggests the need for targeted studies specifically designed for use in
      this approach.

PMID- 7523899
TI  - Mutagenic lifestyles? A review of evidence of associations between germ-cell
      mutations in humans and smoking, alcohol consumption and use of 'recreational'
      drugs.
AB  - In humans, associations between germ-cell mutations and hypothetical aetiological
      factors can be investigated by (1) examining the relationship between the factor
      of interest and conditions known to be of genetic aetiology; (2) examining the
      relationship between conditions of unknown aetiology and route of exposure,
      especially paternal preconceptional exposure. As regards smoking, alcohol and
      'recreational' drugs, the first approach has been applied in studies of
      retinoblastoma, Wilms' tumour and chromosomal anomalies. Only Down's syndrome has
      received intensive investigation, in relation to maternal smoking during
      pregnancy; the relative risks would be compatible with there being no association
      in all recognized conceptuses. The second approach has been applied in studies of
      sperm quality, miscarriage, congenital anomalies and childhood cancer. The
      available studies do not show a consistent relationship between smoking and sperm
      quality; there are few data on the effects of the other exposures. There are a
      substantial number of studies of childhood cancer and smoking by the father; the
      majority do not indicate any relationship. Some studies of childhood cancer
      suggest a positive association with use of 'recreational' drugs by the parents,
      but it has not been possible to clarify which route of exposure, or the specific
      type of drug which may be involved. Use of molecular techniques to detect
      individual genetic changes should enable progress to be made in elucidating the
      origin of mutation. In the meantime, public health actions are justified on the
      basis of the known non-genetic effects of these agents.

PMID- 7523900
TI  - PALS (pregnancy and lifestyle study): association between occupational and
      environmental exposure to chemicals and reproductive outcome.
AB  - A prospective study examined the reproductive outcome, live birth, miscarriage or
      9 months infertility, in 585 participating couples. Examination of the data
      relating to environmental and occupational exposure to chemicals and radiation
      revealed the following associations. Infertility was significantly associated
      with male factors of age, occupational exposure to dusts and occupation of
      labourer in men aged 35 or older. Female factors associated with infertility were
      age and home renovating if aged 35 or older. First trimester spontaneous
      miscarriage was associated with male factors of age, X-rays of the abdomen or
      back, occupation as a tradesperson, home exposure to glues, oil paints or oven
      cleaners. Female factors included age, visiting factories in the course of work,
      X-rays of the abdomen, home use of glues and working at home if aged less than
      35. The most significant findings of the study are the poor outcomes associated
      with abdominal/back X-rays and home exposure to chemicals. The possible effects
      of having different numbers of positive factors was examined for each of
      miscarriage and 9 months infertility. Nine factors were examined for miscarriage
      and couples were found to have from zero to seven of these. The observed rate of
      pregnancy loss ranged from 3.7% to 75% with increasing numbers of factors. For
      infertility, four factors were examined and couples were found to have from zero
      to four of these. The observed rate of 'infertility' ranged from 8.4% to 33.3%
      with increasing numbers of factors. The statistical significance of both sets of
      results is p = < 0.0001. The effects of these exposures on outcome is thus
      cumulative.

PMID- 7523901
TI  - The use of purified DNA repair proteins to detect DNA damage.

PMID- 7523903
TI  - Assessment of cytogenetic changes in human populations at risk in Egypt.
AB  - Humans are exposed to numerous environmental agents that can increase the
      probability of mutagenicity and carcinogenicity. Most of environmental exposures
      involve concurrent or sequential exposure to several agents in air, water, and
      food. Interactive effects in carcinogenesis have been described for a certain
      number of combinations of agents. They are described in terms of enhancement or
      inhibition of carcinogenesis. Risk assessment of exposure to environmental agents
      can start either from laboratory studies after exposure to different agents or
      from epidemiological studies in relation to actual exposure. The use of
      genotoxicity testing is essential for assessment of potential human toxicity so
      that hazards can be prevented. Cytogenetic monitoring of human populations
      exposed to environmental agents has proved to be a useful tool for detecting
      their mutagenic effects. Cytogenetic analysis of human chromosomes in peripheral
      lymphocytes allows direct detection of mutation in somatic cells. Various methods
      can be used for chromosomal analysis (conventional chromosomal analysis, sister
      chromatid exchange, micronucleus frequency detection). Micronucleus frequency can
      be detected either in peripheral blood lymphocytes or in exfoliated cells.
      Different examples of human population studies are presented in this review.
      Several problems which are found in biomonitoring studies are discussed.

PMID- 7523902
TI  - Phenotypic and cytogenetic studies in self-poisoned patients.
AB  - Persons who attempt suicide by taking high doses of chemicals but survive may
      represent an appropriate human model of mutagenesis epidemiology for the study of
      somatic and germinal mutagenicity of drugs, pesticides and other chemicals. The
      most important results of systematic studies in self-poisoning individuals over
      the last 20 years are summarized. Trichlorfon and diazepam caused a higher rate
      of aneuploidy in peripheral lymphocytes. The frequency of chromatid aberrations
      was lower in self-poisoned pregnant women than in self-poisoned non-pregnant
      women and these findings suggest a possible protective effect of pregnancy.
      Intrauterine growth retardation was found in children born after self-poisoning.

PMID- 7523904
TI  - On the frequency of chromosome exchanges in a control population measured by
      chromosome painting.
AB  - Chromosome painting has been shown to be a valid and rapid method for quantifying
      structural chromosome rearrangements in human lymphocytes. The method is
      particularly useful for detecting stable aberrations which are difficult and
      expensive to quantify with classical methods. The inherent stability of
      translocations has enabled them to be used as a biodosimeter for chronic and
      temporally displaced exposure to radiation. Translocations may also be useful for
      quantifying chronic exposure to other environmental agents which may result in an
      accumulation of cytogenetic damage with age. Most exposures are chronic and occur
      at low rates, and conventional cytogenetic methods such as dicentric analysis are
      not expected to be informative. To understand the extent to which age and
      lifestyle factors impact the frequency of stable aberrations, we have performed
      chromosome painting on metaphase-arrested lymphocytes cultured from 47 healthy
      adults ranging in age from 19 to 77 years, and from umbilical cord blood obtained
      from eight healthy full-term infants. All subjects had previously been screened
      to eliminate those who had received significant occupational or accidental
      exposure to radiation or chemicals, and none had received chemo- or radiotherapy.
      Due to the infrequent occurrence of stable aberrations in peripheral lymphocytes,
      we analyzed the equivalent of more than 1100 metaphase cells from each of these
      55 people. An average of one cell in 130 (0.77%) was observed to have a
      translocation or a stable insertion. A significant relationship between stable
      aberrations and the square of the age is apparent (R2 = 0.69, Y = 0.0615 +
      0.000304 age2; p < 0.00001). These results support the hypothesis that stable
      aberrations accumulate with time, and are likely to integrate adverse
      environmental exposure.

PMID- 7523906
TI  - Spontaneous and induced micronuclei and UDS in peripheral lymphocytes.
AB  - We have examined the distributions both of spontaneous and X-ray-induced
      micronuclei (MN) and of spontaneous and UV-induced unscheduled DNA synthesis
      (autoradiographic grains; UDS) in cultures of peripheral blood lymphocytes from
      normal, healthy human volunteers. While the spontaneous MN and UDS do not differ
      significantly from the expected Poisson distributions, both the induced MN and
      UDS are strongly overdistributed (i.e., variance much greater than mean). This
      not only must be allowed for in statistical tests used for population monitoring,
      but offers suggestive evidence that there are large differences in radiation
      response from sample to sample, some of which may reflect true differences among
      normal, healthy subjects.

PMID- 7523905
TI  - Sex is an important variable affecting spontaneous micronucleus frequency in
      cytokinesis-blocked lymphocytes.
AB  - The micronucleus frequency in cytokinesis-blocked lymphocytes of 152 females and
      113 males aged between 20 and 89 years (minimum of 15 subjects per sex per
      decade) was compared. Marked differences in the micronucleus frequency of males
      and females were observed: (a) there was a greater dispersion in the results for
      females when compared to males in all age groups older than 40 years; (b) there
      was a significant positive correlation between micronucleus frequency and age in
      both sexes (p < 0.0001) but the slope of the linear regression line was steeper
      in females (slope = 0.499 micronuclei/year) compared to males (slope = 0.289
      micronuclei/year) (p < 0.0045); (c) the micronucleus frequency in females (Mf)
      was significantly higher than the micronucleus frequency in males (Mm) in all
      decades examined (p < 0.05), the Mf,Mm ratio varied between 1.47 and 1.65 (mean
      +/- 1 SEM = 1.53 +/- 0.03) and showed no trend with age. These results suggest
      that an added mechanism, possibly the loss of X chromosomes, is contributing to
      the micronucleus frequency in females and highlights the importance of sex as a
      variable that has to be taken into consideration when interpreting data from
      cross-sectional studies utilising the cytokinesis-block micronucleus assay as a
      biomarker of chromosome damage.

PMID- 7523907
TI  - The effect of T-lymphocyte 'clonality' on the calculated hprt mutation frequency
      occurring in vivo in humans.
AB  - The frequency of 6-thioguanine resistant (TGr) mutant T-lymphocytes arising in
      vivo in humans can be quantified with a cell cloning assay. However, the in vivo
      proliferation of T-lymphocytes that may include TGr mutant cells can distort the
      relationship between mutation events and the resulting frequency of mutant cells.
      The T-cell receptor (TCR) gene rearrangement pattern of T-cell colonies can be
      used as an independent measure of clonality. Analysis of T-cell 'clonality' in
      413 wild type and 1736 TGr mutant isolates from 58 individuals shows that mutant
      clonality is a frequent occurrence (35/58 individuals = 60.3%). However, a major
      effect on the mutant frequency corrected for clonality (the calculated 'mutation
      frequency') was found only in nine samples all of which had mutant frequencies
      greater than 40 x 10(-6).

PMID- 7523909
TI  - Measurement of frequencies of HPRT mutants, chromosomal aberrations, micronuclei,
      sister-chromatid exchanges and cells with high frequencies of SCEs in
      styrene/dichloromethane-exposed workers.
AB  - Frequencies of HPRT mutants (MFs), chromosomal aberrations with or without gaps
      (CA+; CA-), aberrant cells (AC), micronuclei (MN), sister-chromatid exchanges
      (SCEs) and cells with high frequencies of SCEs (HFCs) were measured in
      lymphocytes collected from 46 workers occupationally exposed to styrene and
      dichloromethane (DCM = methylene chloride). These parameters were also determined
      in 23 controls. Time-weighted average (TWA) values for styrene and DCM exposure
      during an 8-h working day were respectively 70 mg/m3 (range: 0-598) and 108 mg/m3
      (range: 0-742). These values correspond to TWA values of 17 ppm styrene and 31
      ppm DCM. In exposed workers, all cytogenetic parameters were significantly
      enhanced (P < 0.0001; one-sided), but, due to the lack of appropriate control
      data, no definite conclusions could be drawn concerning the mutagenicity of
      styrene/DCM exposure. Duration of exposure was not correlated with genetic
      effects analyzed. The TWA value for styrene was not correlated with the extent of
      genetic damage detected, but the TWA value for DCM was positively correlated with
      the frequencies of chromosome aberrations (with gaps) and aberrant cells. These
      observations make it difficult to decide whether styrene or DCM, or both
      chemicals, induced the cytogenetic effects observed in exposed workers. Using the
      present styrene/DCM data, earlier ethylene oxide data and unpublished
      epichlorohydrin data, the relative sensitivity of the genetic endpoints to detect
      genotoxic exposure was: HFC > CA- > CA+ > SCE > MN > HPRT.

PMID- 7523910
TI  - Detection of human exposure to carcinogens by measurement of alkyl-DNA adducts
      using immunoaffinity clean-up in combination with gas chromatography-mass
      spectrometry and other methods of quantitation.
AB  - A brief overview is given of recent developments from our laboratory in the use
      of immunoaffinity clean-up in the determination of alkyl-DNA adducts. Compound-
      and group-specific antibodies have been prepared against 7-alkylguanines and 3
      alkyladenines. The antibodies were attached to solid supports to make
      immunoaffinity columns which could then be used to selectively purify either
      single adducts or groups of adducts prior to quantitation by various methods. In
      the case of methyl adducts quantitation was achieved by ELISA (3-methyl-adenine,
      using a monoclonal antibody) and HPLC-electrochemical detection (7
      methylguanine). For groups of adducts, quantitation of the individual compounds
      was effected by gas chromatography-mass spectrometry (3-alkyladenines, using
      deuterated analogues of each adduct as an internal standard) and HPLC
      fluorescence detection (7-alkylguanines). In all of these cases efficient
      purification of adducts from urine or DNA hydrolysates could be easily carried
      out. Using these techniques human exposure to alkylating agents in tobacco smoke
      and from cancer chemotherapy has been studied.

PMID- 7523908
TI  - An analysis of in vivo hprt mutant frequency in circulating T-lymphocytes in the
      normal human population: a comparison of four datasets.
AB  - In this paper, we have compared mutant frequency data at the hprt locus in
      circulating T-lymphocytes from four large datasets obtained in the UK (Sussex),
      the USA (Vermont), France (Paris) and The Netherlands (Leiden). In total, data
      from > 500 non-exposed individuals ranging in age from newborns (cord blood
      samples) to > 80 years old have been included in the analysis. Based on raw data
      provided by the four laboratories, a model is presented for the analysis of
      mutant frequency estimations for population monitoring. For three of the
      laboratories, a considerable body of data was provided on replicate estimates of
      mutant frequency from single blood samples, as well as estimates from repeat
      blood samples obtained over a period of time from many of the individual
      subjects. This enabled us to analyse the sources of variation in the estimation
      of mutant frequency. Although some variation was apparent in the results from the
      four laboratories, overall the data were in general agreement. Thus, in all
      laboratories, cellular cloning efficiency of T-cells was generally high (> 30%),
      although in each laboratory considerable variation between experiments and
      subjects was seen. Mutant frequency per clonable T-cell was in general found to
      be inversely related to cloning efficiency. With the exception of a few outliers
      (which are to be expected), mutant frequencies at this locus were in the same
      range in each dataset; no effect of subject gender was found, but an overall
      clear age effect was apparent. When log mutant frequency was analysed vs log (age
      + 0.5) a consistent trend from birth to old age was seen. In contrast, the effect
      of the smoking habit did differ between the laboratories, there being an
      association of smoking with a significant increase in mutant frequency in the
      Sussex and Leiden datasets, but not in those from the Vermont or Paris datasets.
      Possible reasons for this are discussed. One of the objectives of population
      monitoring is an ability to detect the effect of accidental or environmental
      exposure to mutagens and carcinogens among exposed persons. The large body of
      data from non-exposed subjects we have analysed in this paper has enabled us to
      estimate the size of an effect that could be detected, and the number of
      individuals required to detect a significant effect, taking known sources of
      variation into account.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7523911
TI  - 32P-postlabelling analysis of DNA adducts in humans: adduct distribution and
      method improvement.
AB  - 32P-Postlabelling was applied to study the distribution of adducts in white blood
      cells of foundry workers exposed to polycylic aromatic hydrocarbons. The
      distribution of the adducts among 63 workers followed an apparently trimodal
      pattern, which could relate to polymorphism in PAH metabolism. A modified
      postlabelling method is described and some parameters were tested for optimal
      labelling. The total volume of the polynucleotide kinase reaction is 2
      microliters, which decreases exposure to radioactivity and costs of isotopes.

PMID- 7523912
TI  - DNA adducts in cervical tissue of smokers and non-smokers.
AB  - Cervical biopsy samples were taken from 40 women, aged between 31 and 72,
      undergoing hysterectomies. Twenty-two of the women were smokers, four were ex
      smokers and 14 were non-smokers. DNA was isolated and analysed using 32P
      postlabelling, after butanol extraction or nuclease P1 digestion enhancement of
      the adducts. Resolution of the adducts was by thin-layer chromatography on
      polyethyleneimine (PEI)-cellulose. The pattern of adducts seen was similar to
      smoking-related adducts detected in other tissues and consisted mainly of a
      diagonal zone of radioactivity. With the butanol extraction enrichment method,
      the levels of adducts in DNA from the 22 smokers ranged from 1.65 to 6.04
      adducts/10(8) nucleotides (mean = 3.70, SD = 1.36), in DNA from non-smokers from
      1.16 to 3.98 (mean = 2.04, SD = 0.77) and in samples from ex-smokers from 2.57 to
      3.35 (mean = 2.86, SD = 0.37). The increase in adduct levels in smokers compared
      with non-smokers was highly significant (Mann-Whitney test p = 0.0005, two
      tailed). When analysed by the nuclease P1 digestion enhancement method, total
      adduct levels in samples from smokers (mean = 2.95, SD = 1.77) were not
      significantly different (p = 0.3, two-tailed) from levels in non-smokers (mean =
      2.34, SD = 0.96). However, the level of a minor discrete adduct spot was
      significantly lower (p = 0.02, two-tailed) in smokers (mean = 0.19, SD = 0.36)
      than in non-smokers (mean = 0.39, SD = 0.41). The results indicate that some of
      the DNA adducts detected in cervical epithelium correlate with tobacco smoking
      and support the hypothesis that smoking-related cervical cancer results from
      exposure to genotoxic components of cigarette smoke that become activated to DNA
      binding products in this tissue.

PMID- 7523913
TI  - Uptake and metabolism of ethene studied in a smoke-stop experiment.
AB  - Knowledge of the relationships between exposure levels and levels of hemoglobin
      adducts are essential when the latter are to be used for exposure monitoring or
      risk estimation, the hygienic control being based on measurements of exposure.
      These ratios are mostly very uncertain, mainly due to difficulties of determining
      the time-weighted average exposure concentration. A solution to this problem has
      been suggested involving adduct measurement before and after two consecutive
      periods of about 1 week, the first with absence from exposure, the second with
      careful measurement of exposure. This model was tested in two smokers who
      abstained from smoking for one week. Analysis of inhaled ethene and of adducts
      from ethylene oxide (EO) to N-terminal valine of hemoglobin are compatible with
      metabolism of 2% of inhaled ethene to EO and a detoxification rate of 1 h-1 of
      EO.

PMID- 7523915
TI  - Special issue: Human monitoring II.

PMID- 7523914
TI  - Lymphocyte replicating ability in individuals exposed to arsenic via drinking
      water.
AB  - A human monitoring study was carried out to explore the effect on lymphocyte
      proliferation of chronic exposure to arsenic (As) via drinking water. Blood and
      urine samples were taken from volunteers from a town where levels of As in the
      drinking water averaged 412 micrograms/l, and from a matched group of
      individuals, with similar socioeconomic status, that drank water with As average
      levels of 37.2 micrograms/l. Exposure was assessed by questionnaires and by
      determining the levels of As in urine and water samples. The evaluation of the
      peripheral blood lymphocyte proliferation was done at different culture times
      using labelling (LI), mitotic (MI) and replication indexes (RI) as endpoints. No
      significant differences were seen for either LI or MI, except for MI in 72 h
      cultures and in LI in males and females with skin lesions vs. those without
      lesions. Significant differences in RI were seen for exposed females but not for
      males. Correlations between LI and MI showed that progression from the initial S
      to M-phase is altered in exposed individuals. Arsenic exposure as well as lead
      and mercury affect cellular immune response, making the endpoints of cell
      proliferation variables of interest in population monitoring study design, since
      they might provide information in health impairment due to exposure, which is
      important in risk assessment.

PMID- 7523916
TI  - Mutagenicity of mono- and dinitropyrenes in the Salmonella typhimurium TM677
      forward mutation assay.
AB  - Nitropyrenes are a group of widespread environmental pollutants, some of which
      are highly potent as bacterial and mammalian cell mutagens and as animal
      carcinogens. A quantitative bacterial forward mutation assay, based on resistance
      to 8-azaguanine (8-AG) in Salmonella typhimurium TM677, was employed as an
      alternative to reversion assays to reexamine the mutagenicity of 1-, 2-, and 4
      nitropyrene (1-, 2-, and 4-NP) and 1,3-, 1,6-, and 1,8-dinitropyrene (1,3-, 1,6-,
      and 1,8-DNP) in the presence and absence of rat liver postmitochondrial
      supernatant (PMS). The major finding is that 2-NP, reported as a potent mutagen
      in the absence of PMS in bacterial reversion assays, was inactive in the absence
      of PMS in this assay. However, 2-NP was mutagenic in the presence of PMS. The
      implications of this observation with respect to sample purity and the metabolism
      of 2-NP are discussed. Without PMS the following minimum detectable mutagen
      concentration (MDMC) potency series expressed as nmol/ml was obtained: 1,8-DNP
      (0.5 x 10(-3)), 1,6-DNP (1.2 x 10(-3)), 1,3-DNP (2.3 x 10(-3)), 4-NP (0.2), 1-NP
      (0.2), 2-NP (> 1200), pyrene (> 1500). With PMS the potency series was: 1,6-DNP
      (0.7), 1,8-DNP (2.1), 4-NP (2.2), 2-NP (2.6), 1,3-DNP (3.7), 1-NP (4.6), pyrene
      (> 1500). With the exception of 2-NP, all the nitropyrenes were more mutagenic
      without PMS than with PMS. The greatest difference was observed with the
      dinitropyrenes, which were three orders of magnitude less potent in the presence
      of PMS. Pyrene, often reported as a bacterial mutagen in the presence of PMS, was
      nonmutagenic in this assay when a purified sample was tested.

PMID- 7523917
TI  - Human cell mutagenicity of mono- and dinitropyrenes in metabolically competent
      MCL-5 cells.
AB  - Nitropyrenes are ubiquitous environmental pollutants that may pose a human health
      hazard because some are highly potent mutagens and carcinogens. The mutagenicity
      (trifluorothymidine resistance at the thymidine kinase locus) of 1-, 2-, and 4
      nitropyrene (1-, 2-, and 4-NP), 1,3-, 1,6-, and 1,8-dinitropyrene (1,3-, 1,6-,
      and 1,8-DNP), and pyrene was assessed in a quantitative forward mutation assay
      using a metabolically competent line (MCL-5) of human B-lymphoblastoid cells.
      These cells contain endogenous cytochrome P450 activity (CYP1A1) and two plasmids
      that express cDNAs for four additional P450s (CYP1A2, CYP2A6, CYP2E1, CYP3A4) and
      microsomal epoxide hydrolase found in human liver. The major finding is that 2-NP
      and 1,3-DNP, both potent bacterial mutagens, were nonmutagenic in this assay. The
      following mutagenic potency series, expressed as the minimum detectable mutagen
      concentration (MDMC) in nmol/ml, was obtained: 1,6-DNP (0.8), 1,8-DNP (1.5), 4-NP
      (3.1), 1-NP (9.1), 2-NP (> 81), 1,3-DNP (> 86), pyrene (> 494). There was over an
      11-fold difference between the most potent (1.6-DNP) and the least potent (1-NP)
      mutagen. 1,6-DNP was approximately twice as mutagenic as 1,8-DNP, which was
      almost twice as mutagenic as 4-NP, which, in turn was nearly three times as
      potent as 1-NP. This is the first report on the testing of 2-NP and 4-NP for
      mutagenicity in mammalian cell cultures. The human cell mutagenicity of these
      compounds was discussed in terms of potency series of nitropyrenes obtained from
      animal carcinogenicity experiments and other mammalian cell mutagenicity assays.

PMID- 7523919
TI  - Effects of dietary restriction on induction of unscheduled DNA synthesis (UDS)
      and replicative DNA synthesis (RDS) in rat liver.
AB  - The effects of dietary restriction on the induction of unscheduled DNA synthesis
      (UDS) and replicative DNA synthesis (RDS) were studied in the hepatocytes of F344
      rats exposed in vivo to dimethylnitrosamine (DMN) or CCl4. The animals were given
      food ad libitum, a restricted amount of food (4 g/rat/overnight) or no food.
      Hepatocytes were isolated 2 h after oral administration of DMN at a dose of 5
      mg/kg body weight and 48 h after oral administration of CCl4 at a dose of 400
      mg/kg body weight, and incubated for 4 h in Williams' medium E supplemented with
      either [3H]thymidine for UDS or 5-bromodeoxyuridine for RDS. UDS was determined
      by autoradiography and RDS was determined by the immunoenzymatic staining method.
      The background levels of UDS (net grains/nucleus) and RDS (cells in S phase) in
      control were -12.4 and 0.64% for ad libitum feeding, -6.8 and 0.04% for
      restricted feeding, and -8.1 and 0% for fasting. UDS induced by DMN and RDS
      induced by CCl4 were 19.4 and 3.3% for ad libitum feeding, 34.5 and 10.4% for
      restricted feeding, and 47.8 and 15.1% for fasting. DMN demethylase activity in
      rat liver was also found to increase with dietary restriction. These results
      indicate that dietary restriction modulates the responses of UDS and RDS in the
      liver of rats.

PMID- 7523920
TI  - Applicability of alternative models of revertant variance to Ames-test data for
      121 mutagenic carcinogens.
AB  - Models of sampling variance in replicate revertant scores play a role in analyses
      of Ames-test data on mutagenicity in Salmonella, both in modeling the dose
      response relation and in estimating initial dose-response slope or 'potency',
      e.g., for use in correlating mutagenic and carcinogenic potencies among different
      chemicals. Both generalized Poisson (GP) and negative binomial (NB) models of
      revertant variance have been applied in this way, but their empirical
      applicability has only been assessed using Ames-test data on a few chemicals. The
      applicability of these and related variance models was therefore assessed for
      1905 such data sets pertaining to 121 putatively mutagenic carcinogens. Only
      approximately 50% of the data sets analyzed were found to involve a significantly
      positively correlated dose-response, and < 50% were found to exhibit a plausibly
      heterogeneous response variance regardless of dose-response correlation. Among
      data sets with plausibly heterogeneous variance, < 60% were found to exhibit
      significantly extra-Poisson variability. Among the significantly extra-Poisson
      data sets, most (> 75% among dose-response correlated data sets) were found to
      exhibit revertant variance consistent with both the GP and NB models; while the
      GP model was found to be somewhat more consistent with these data, the NB model
      more often gave a nominally better fit when both models were consistent.
      Implications of these results for the design of methods used to analyze Ames-test
      data are discussed.

PMID- 7523921
TI  - Assessment of toxicity, clastogenicity, mutagenicity and transforming activity of
      pentoxifylline in mammalian cells cultured in vitro.
AB  - We tested the possible cytotoxic, clastogenic and genotoxic effects of
      pentoxifylline on different lines of mammalian cells cultured in vitro. This
      study was part of the developmental research of agapurin, since pentoxifylline
      represents an effective compound of this drug. Cells treated for a short time
      manifested a relatively high resistance to the toxic effects of pentoxifylline.
      Generally, only cells treated for a long time (18 h) or a short time (2 h) with
      high concentrations of drug manifested sensitivity to the toxic effects of
      pentoxifylline. Although the tested drug induced DNA synthesis inhibition in V79
      and EUE cells and clastogenic effects in V79 cells, it was not able to induce
      either 6-TGr mutations in the HGPRT locus of V79 cells or morphological
      transformation of Syrian hamster embryo cells. Adding of microsomal fraction S9
      to the treated cells did not markedly change the effects of pentoxifylline on
      different studied endpoints. We suggest that pentoxifylline has no genotoxic
      effects, and that the cytotoxicity and induction of chromosomal aberrations were
      induced by inhibition of cellular DNA replication.

PMID- 7523922
TI  - Clastogenic action of thiotepa on bone marrow cells of the Armenian hamster.
AB  - Thiotepa (TT) induced chromosomal aberrations in the bone marrow cells of the
      Armenian hamster, Cricetulus migratorius, in a dose-dependent manner. The maximal
      clastogenic action was observed 24 h after treatment with thiotepa. Male and
      female Armenian hamsters were similarly sensitive to the clastogenic action of
      thiotepa. The lowest effective concentration of thiotepa for Armenian hamsters
      was 2.5 mg/kg b.w. (6.1% of the LD50). The results obtained and analysis of the
      literature data have shown that Armenian hamsters are much more resistant to the
      clastogenic action of thiotepa than various other species of rodent. This
      resistance is not due to the metabolic activation rates of chemical mutagen in
      the liver of Armenian hamsters, since thiotepa is a direct-acting clastogen.

PMID- 7523923
TI  - In situ and suspension protocols for chemically-induced mutation at the tk locus
      in L5178Y MOLY cells: dose response and colony size distribution.
AB  - We used EMS up to concentrations of 0.25 microliters/ml (292 micrograms/ml) to
      induce mutations at the tk locus in L5178Y MOLY cells, measured the cellular
      response by the in situ mutation assay protocol and compared these results to
      those obtained in a concomitant suspension assay. EMS induced mutagenic responses
      with both protocols. The mutant fraction for the solvent control was 89 mutants
      per million viable colonies for the suspension protocol and 426 mutations per
      million viable cells plated for the in situ protocol. These numbers increase to
      447 and 2073 respectively, with 0.25 microliter/ml EMS treatment. Sizing curves
      indicated that the in situ protocol detected a greater proportion of smaller
      colonies than did the suspension protocol. Not only were the number of small
      colonies greater than large colonies in the in situ protocol, but their rate of
      increase was also slightly higher than that of the large colonies. The in situ
      protocol also reduces the time and cost of experimentally performing the assay
      compared to the suspension protocol. In this paper we compare the use of the
      suspension and in situ protocols to measure chemically-induced mutations and
      demonstrate that the latter method detects a larger fraction of induced mutations
      at the tk locus in L5178Y MOLY cells.

PMID- 7523924
TI  - Adaptive response induced by mitomycin C measuring the frequency of SCEs in human
      lymphocyte cultures.
AB  - The induction of an adaptive response was obtained using mitomycin C (MMC) as
      both stimulating and challenging agent. Human lymphocyte cultures of two female
      donors were treated with 5, 10 and 20 ng/ml of MMC as conditioning doses. For the
      challenging treatments two different protocols were used (200 ng/ml for 4 h, and
      400 ng/ml for 1 h). The scoring of sister chromatid exchanges (SCE) in the first
      challenging combination showed the following inhibition related with the expected
      SCE damage: 49.2%, 51.4%, and 36.9% for one donor, and 42.0%, 38.6%, and 34.7%
      for the other (corresponding to the stimulating dosages 5, 10, and 20 ng/ml,
      respectively). The second challenging combination gave an inhibition of 53.8%,
      40.5% and 30.2% in one donor and 43.2%, 45.9% and 30.3% in the other donor.

PMID- 7523925
TI  - Co-purification of gastric mucoproteins with DNA: an explanation for the reported
      'interaction' of omeprazole with DNA in rat tissues.
AB  - Recently, Phillips et al. reported that small amounts of radioactivity derived
      from [14C]omeprazole were 'associated' with DNA purified from gastrointestinal
      tissues of treated rats (Mutagenesis 7, 277-283, 1992). We hypothesized that this
      radioactivity arose from omeprazole bound to contaminating protein in the DNA
      fraction (Mutagenesis 7, 395-396, 1992). Using rats injected with 35S-labeled
      amino acids, we found significant protein contamination (0.06 microgram of
      protein per microgram of DNA) in DNA purified from gastrointestinal tissues.
      Gastric mucous proteins represent likely candidates for binding of omeprazole in
      the rat model used by Phillips et al. To investigate this, we partially purified
      proteins from gastric mucus, incubated them with [14C]omeprazole, and then added
      these radiolabeled mucoproteins to homogenates of rat colon and duodenum before
      starting the DNA purification. Detectable amounts of the added mucoproteins
      remained in the DNA fraction, but none of the control protein, bovine serum
      albumin, remained with the DNA. Further characterization of the mucoproteins by
      hydroxyapatite chromatography indicated that a certain population of these
      proteins survived the DNA purification procedures. These data indicate that the
      association of omeprazole with DNA reported by Phillips et al. most probably is
      explained by binding of omeprazole to mucous glycoproteins (or other proteins
      present in the GI tract) that selectively survive DNA purification protocols.

PMID- 7523918
TI  - Genotoxic effects of the o-phenylphenol metabolites phenylhydroquinone and
      phenylbenzoquinone in V79 cells.
AB  - o-Phenylphenol (OPP) and its sodium salt, sodium o-phenylphenate are broad
      spectrum fungicides and disinfectants with widespread usage. Both chemicals have
      been reported to induce cancer in the kidney and urinary bladder of Fischer 344
      rats. Recently it has been proposed that the metabolic activation of OPP occurs
      via a two-step process involving the cytochrome P450-mediated formation of
      phenylhydroquinone (PHQ) in the liver and a prostaglandin H synthase-mediated
      oxidation of PHQ to phenylbenzoquinone (PBQ) in the urinary tract. In order to
      further investigate the metabolic activation and genotoxic effects of OPP, we
      have investigated the ability of PHQ and PBQ to induce micronuclei and mutations
      at the HGPRT locus in a prostaglandin H synthase-containing V79 Chinese hamster
      lung fibroblast cell line. In arachidonic acid-supplemented V79 cells, PHQ
      induced a significant increase in micronuclei whereas no increase was observed in
      cells in the absence of arachidonic acid supplementation. Immunofluorescent
      labeling of centromeric proteins with the CREST antibody indicated that the
      arachidonic acid-dependent induction of micronuclei by PHQ was due almost
      entirely to micronuclei containing whole chromosomes which had failed to
      segregate properly during mitosis. The induction of micronuclei by PHQ was
      significantly inhibited by treatment of the cells with indomethacin, aspirin,
      ascorbic acid, dithiothreitol and reduced glutathione supporting a role for
      prostaglandin H synthase in the genotoxic effects of PHQ. No increase in 6
      thioguanine-resistant cells was observed in cells treated with PHQ or PBQ. This
      arachidonic acid-dependent conversion of PHQ to a genotoxic species is consistent
      with the hypothesis that a prostaglandin H synthase-mediated activation of PHQ
      may be involved in OPP- and SOPP-induced urinary tract carcinogenesis and also
      suggests that the induction of aneuploidy may play an important role in OPP
      induced tumorigenesis.

PMID- 7523926
TI  - Genotoxicity of 2-halosubstituted enals and 2-chloroacrylonitrile in the Ames
      test and the SOS-chromotest.
AB  - 2-Chloroacrolein and 2-bromoacrolein are very potent direct mutagens not
      requiring metabolic activation in Salmonella typhimurium strains TA 100 and TA
      1535. Mutagenic activities decrease with increasing degree of methyl substitution
      at carbon atom C-3 of the acrolein moiety from 2-chloroacrolein via 2
      chlorocrotonaldehyde to 2-chloro-3,3-dimethylacrolein. With 2-chloroacrylonitrile
      equivocal results are obtained in strain TA 100 without S9-mix and unequivocal
      with S9-mix. In the SOS-chromotest the 2-chloroenals are also very strong
      genotoxins and the structure-activity relationships found in the Ames test are
      clearly confirmed. 2-Chloroacrylonitrile is not positive in the SOS-chromotest.
      The mutagenic mechanisms are discussed, and indications are provided that
      genotoxicity/mutagenicity depends on formation of DNA adducts, e.g., 1,N2-cyclic
      deoxyguanosine adducts.

PMID- 7523930
TI  - Induction of chromosomal aberrations with benzon nuclease in Chinese hamster
      ovary (CHO) cells.
AB  - Benzon nuclease, an endonuclease originating from Serratia marcescens, was tested
      for its chromosome breaking activity in Chinese hamster ovary cells. Using a
      permeabilizing method with hypertonic glycerol, benzon nuclease induced
      chromosomal aberrations in an S-phase independent manner. The frequencies of
      polycentric chromosomes were correlated with the dose of the enzyme and the
      intercellular distribution of aberrations was overdispersed.

PMID- 7523927
TI  - Ubiquitous presence of mutagenic and antimutagenic components in air-borne
      particulates of two Japanese cities.
AB  - Previous studies on several samples of urban air-borne particulates showed that
      the long-chain fatty acids present in these samples can interfere with the
      measurement of mutagenicity of the particulates with the Salmonella assay. To
      explore whether this phenomenon is a general, fatty acid contents and the
      mutagenicity (with Salmonella typhimurium TA98 without S9) were measured for 34
      particulate samples collected in the cities of Okayama and Tokyo over a period of
      1 year. Palmitic, stearic, oleic and linoleic acids were found in all these
      samples in this order of amount, and their interference on mutagenicity
      measurement was eminent, particularly at high doses of the sample. With the use
      of blue cotton extraction, the mutagenic components can be freed from most of
      these antimutagenic factors. Significant correlation was found between the number
      of particulates and the mutagenicity per unit volume of the air. Eight polycyclic
      aromatic hydrocarbon compounds, including benzo[alpha]pyrene were quantified for
      these 34 particulate samples. Their contents were too small to account for the
      observed mutagenicity, suggesting that other polycyclic compounds, possibly
      involving nitro aromatics, were responsible for the mutagenicity observed. No
      remarkable differences were noted between Okayama and Tokyo in fatty acid
      contents, mutagenicity or polycyclic aromatic-hydrocarbon contents of the
      samples.

PMID- 7523929
TI  - Differences in the response to mutagens between two V79 sublines.
AB  - Two V79 Chinese hamster sublines (V79-UL and V79-MZ) which differed markedly with
      respect to their spontaneous pattern of mutations at the HPRT locus were
      comparatively investigated in genotoxicity tests with ethyl methanesulphonate
      (EMS). EMS-induced frequencies of HPRT mutations and sister chromatid exchanges
      (SCEs) were much higher in V79-MZ than in V79-UL. V79-MZ were not hypersensitive
      against EMS and had normal frequencies of spontaneous gene mutations and
      chromosome aberrations. Baseline SCE frequencies at various BrdUrd concentrations
      were slightly increased compared to V79-UL. EMS induced a similar amount of
      chromosome aberrations in both cell lines but exchange figures occurred with
      lower frequency in V79-MZ. The results indicate that specific and significant
      differences in the response to mutagens may exist between 'normal' Chinese
      hamster cell lines which might be relevant for genotoxicity testing.

PMID- 7523928
TI  - Nitrite-induced mutations in a forward mutation assay: influence of nitrite
      concentration and pH.
AB  - The mutagenicity of sodium nitrite at three pHs (7.4, 6.4 and 5.4) has been
      investigated by treating a shuttle vector plasmid in vitro and assaying for
      mutations within the supF target gene following replication of the damaged
      plasmid in human Ad293 cells. Mutation frequency increased with increasing
      nitrite concentration and decreasing pH. Among treatments from which a
      significant number of mutants could be collected, the most commonly induced
      mutations were GC-->AT transitions (44-56% of total mutations), followed by GC-
      >TA transversions (24-30%). The types of mutations induced at different nitrite
      concentrations and different pH's were similar, though some differences in their
      distribution throughout the supF gene were noted. These results provide
      information on the types of mutations that may be produced following the
      processing of nitrite-induced DNA damage in human cells.

PMID- 7523931
TI  - The sensitivity of the micronucleus assay for the detection of occupational
      exposure to vinyl chloride monomer.
AB  - The micronucleus assay was performed in the peripheral lymphocytes of 32 subjects
      occupationally exposed to vinyl chloride monomer (VCM) divided into two groups
      according to years of employment. Blood samples were taken in the period from 24
      h to 90 days following a transitory exposure to elevated VCM concentrations of
      300 ppm due to the technological process. In subjects with a longer period of
      employment micronucleus frequencies decreased in proportion to the length of the
      interval after the last exposure to VCM. The results confirm that the
      micronucleus assay can serve as a suitable indicator of the time elapsed after
      last exposure to elevated concentrations of environmental mutagen. It can be
      assumed that duration of employment may contribute to the occurrence of the
      cumulative effect produced by exposure to elevated VCM concentrations.

PMID- 7523933
TI  - Genotoxicity of dithiocarbamates and their metabolites.
AB  - Dithiocarbamate fungicides are widely used in agriculture for protection of
      vegetable crops and seeds. The mutagenicity spectra of ziram, thiram, zineb S-65
      and ETU were determined by employing a battery of test systems included the
      bacterium Salmonella typhimurium (strains TA98, TA100, TA102, TA104, TA1535,
      TA1538), the yeast Saccharomyces cerevisiae (strain D61.M) and the shallot Allium
      ascalonicum somatic cells. Plate incorporation assay with S. typhimurium
      demonstrated direct mutagenicity of ziram in TA100 and thiram in TA100 and TA98
      whereas zineb S-65 and ETU were ineffective. Tests for mitotic chromosome
      malsegregation in S. cerevisiae D61.M gave positive results with thiram, zineb S
      69 and ETU. In shallot somatic root-tip cells ziram, thiram and ETU induced
      different genetic damages e.g. mitotic disturbance, polyploidy and micronuclei.

PMID- 7523934
TI  - RecN SOS gene and induced precise excision of Tn10 in Escherichia coli.
AB  - A mutant defective in the induced excision of Tn10 was isolated by decreased
      papillation on MacConkey-galactose plates with mitomycin C. The mutation involved
      was characterized as recN by genetic mapping and complementation. This mutant, as
      well as a previously characterized recN mutant (recN262), showed a markedly
      decreased frequency of excision of Tn10 after treatment with UV or mitomycin C.
      These observations indicate that recN is involved in the induced excision of
      Tn10.

PMID- 7523935
TI  - Involvement of antipain-sensitive protease activity in suppression of UV
      mutagenicity by human interferon-alpha.
AB  - To study the relationship between the transient elevation of protease activity
      and hypomutability observed in hypermutable human RSa cells pretreated with human
      interferon (HuIFN)-alpha and then irradiated with far-ultraviolet light (UV),
      protease inhibitors capable of specifically inhibiting the activity were
      investigated. Of ten inhibitors tested, antipain showed the greatest inhibitory
      effect. Antipain also prevented the suppression of UV-mutagenicity by HuIFN-alpha
      in RSa and xeroderma pigmentosum-derived fibroblast cells, as shown by culturing
      cells in medium containing antipain immediately after UV exposure and evaluating
      the generation of clones resistant to ouabain- or 6-thioguanine-mediated
      cytotoxicity. Thus, an antipain-sensitive protease may be involved in the
      hypomutability induced by HuIFN-alpha.

PMID- 7523936
TI  - Antimutagenic potential of amniotic fluid from Nigerian women.

PMID- 7523932
TI  - Dose-dependent increase in the frequency of micronuclei and chromosomal
      aberrations by misonidazole in mouse bone marrow.
AB  - Cytogenetic effects produced in bone marrow of mice by various doses of
      misonidazole (MISO, 100 to 1000 mg/kg bodyweight) were studied by assaying the
      induction of micronuclei (MN) and chromosomal aberrations. Misonidazole increased
      the frequency of both micronuclei and chromosomal aberrations over normal at 24 h
      after treatment, however, the values were statistically significant from normal
      only at drug doses above 250 mg/kg. The increase was proportional to the drug
      dose with a best fit to linear quadratic model for MN induction. For chromosomal
      aberrations the data fitted equally well to linear as well as linear quadratic
      models.

PMID- 7523937
TI  - Adriamycin induces large deletions as a major type of mutation in CHO cells.
AB  - Adriamycin (ADR), a commonly used cancer chemotherapy antibiotic, exhibits a
      variety of genotoxicities. In this study, we have examined the mutagenicity of
      ADR at the hypoxanthine-guanine phosphoribosyltransferase gene (hprt) in Chinese
      hamster ovary (CHO) cells and the xanthine-guanine phosphoribosyltransferase
      locus (gpt) in a pSV2gpt-transformed CHO cell line, AS52. Although ADR induced a
      dose-dependent increase of mutant frequency at both loci, it was more mutagenic
      to the gpt gene than to the hprt locus. Multiplex PCR analysis revealed that 35%
      of the 103 independent ADR-induced HPRT-deficient mutants carried large
      deletions. Among these deletion mutants, 33% were total gene deletions, 22%
      affected multiple exons, and 42% involved a single exon, of which most (9/15)
      were exon 1. The majority (63%) of ADR-induced AS52 mutants had a total deletion
      of the gpt gene. These observations indicate that ADR induces large deletions as
      a major type of gene mutation in mammalian cells, suggesting the involvement of
      reactive oxygen species as one mutagenic pathway in the mutagenesis of ADR.

PMID- 7523938
TI  - Mutagenicities of Bangkok and Tokyo river waters.
AB  - Samples of water from the Chao Phraya river and some connected canals in Bangkok,
      Thailand, and from the Sumida and Ara rivers in Tokyo, Japan, were tested for
      mutagenicity using blue rayon to adsorb the mutagens. The samples from the Chao
      Phraya river and connected canals at sites located 50-150 km from the river mouth
      taken in May 1993 showed a mutagenicity of 87-1213 revertants per 0.05 g blue
      rayon extract towards S. typhimurium YG1024 in the presence of S9 mix. Samples
      from most sites taken in December 1993, which follows the rainy season, showed a
      lower mutagenicity than those taken in May, possibly due to dilution by the
      larger volume of water in the river and canals in December. Water samples from
      the Sumida river were collected in July 1993 and February 1994, and those from
      the Ara river in January 1994. Mutagenicity of samples from all sites of the
      Sumida and Ara rivers, which were located 2-30 and 2-20 km, respectively, from
      the river mouth was also clearly detected in the presence of S9 mix and did not
      differ much, being 155-748 revertants of YG1024 per 0.05 g blue rayon extract.
      These results demonstrated that the water in all three rivers contained some
      frameshift mutagens.

PMID- 7523939
TI  - Study of the genotoxic activity of five chlorinated propanones using the SOS
      chromotest, the Ames-fluctuation test and the newt micronucleus test.
AB  - Three short-term assays (the SOS chromotest, the Ames-fluctuation test and the
      newt micronucleus test) were carried out to evaluate the genotoxicity of five
      chlorinated propanones identified in several chlorinated waters
      (monochloropropanone, 1,1-dichloropropanone, 1,3-dichloropropanone, 1,1,1
      trichloropropanone and 1,1,3-trichloropropanone). In the SOS chromotest, all the
      compounds except monochloropropanone were found to induce primary DNA damage in
      Escherichia coli. With the fluctuation test, all five chloropropanones showed
      mutagenic activity on Salmonella typhimurium strain TA100. The newt micronucleus
      assay detected a clastogenic effect on the peripheral blood erythrocytes of
      Pleurodeles waltl larvae only for 1,3-dichloropropanone and 1,1,3
      trichloropropanone. Moreover, two structure-activity relationships are
      noticeable: (1) chloropropanones with chlorine substituents on both carbon
      positions (1,3-DCP and 1,1,3-TCP) are by far more genotoxic than chloropropanones
      substituted only on one carbon position (1,1-DCP and 1,1,1-TCP); (2) the increase
      of the number of chlorine substituents decreases the mutagenic activity
      (fluctuation test) of the chlorinated propanones studied.

PMID- 7523940
TI  - Studies on mutations in male germ cells of transgenic mice following exposure to
      isopropyl methanesulfonate, ethylnitrosourea or X-ray.
AB  - Transgenic mice have recently been used for mutagenesis assays in vivo. The
      present study was undertaken to clarify whether such assays can detect mutations
      induced after treatment of male germ cells in mouse with isopropyl
      methanesulfonate (iPMS), ethylnitrosourea (ENU) or X-ray irradiation. The
      transgenic mice used for assay are Muta Mouse (MM) strain, which carries 80
      copies of the bacterial lacZ gene per cell as targets for mutagenesis. Male MM
      animals were given a single intraperitoneal injection of 200 mg/kg iPMS, 150
      mg/kg ENU or were irradiated with 500 rads of X-rays. Vasa deferential sperm,
      caudal epididymal sperm and/or whole testes were extracted at various times after
      treatment with each agent. After the genomic DNA was extracted from each tissue,
      mutation analysis at the lacZ locus was carried out by the method of Myhr et al.
      The spontaneous lacZ- mutant frequencies were on the order of 10(-5)-10(-6). The
      lacZ- mutant frequencies in all treatment groups were increased over the control
      animals. The iPMS-induced mutant frequency in postmeiotic stages was low.
      However, ENU induced relatively high mutant frequencies in the spermatogonia. X
      rays induced mutant frequencies in the late spermatid and early spermatid stages
      that were higher than the mutant frequencies in spermatogonia. Mutant frequencies
      in MM detected after treatment of male germ cells with ENU or X-rays were lower
      than mutant frequencies detected by the mouse specific-locus test in previous
      reports. Hence, considering the lower resolution power of the transgenic animal
      mutagenesis assays using the target lacZ gene compared with the specific locus
      test, to detect mutations induced in male germ cells, it is not clear whether
      this assay is a practical alternative to the specific locus test.

PMID- 7523942
TI  - Induction of micronuclei by acute and chronic exposure in vivo to gamma rays in
      murine polychromatic erythrocytes.
AB  - The effect on micronuclei (MN) frequency of in vivo exposure to different dose
      rates of gamma rays in murine polychromatic erythrocytes (PCE) was studied.
      Groups of animals were irradiated with 1.0 Gy of gamma rays administered in 10,
      100, 1000 or 10,000 min; the micronucleated polychromatic-erythrocytes (MN-PCE)
      frequency was scored in blood samples obtained from the tail of mice at various
      times before, during or after irradiation. The time-response curves for the 10,
      100, and 1000 min exposure were similar; however, the two first curves showed a
      peak at 1800 min and the last at 2400 min after exposure. The curve obtained from
      the 10,000 min exposure showed a plateau for a long period during and after the
      exposure. However, the integration of the area under the curves indicates that
      the damage caused by the different radiation protocols was the same, suggesting
      that throughout time, the lesions were not repaired but rather diluted by cell
      division.

PMID- 7523941
TI  - In vivo genotoxic interactions among three phenolic benzene metabolites.
AB  - Three benzene metabolites, hydroquinone (HQ), cathecol (CAT) and phenol (PHE)
      were studied to define their possible interaction in inducing micronuclei (Mn) in
      mouse bone marrow polychromatic erythrocytes (PCEs). HQ and CAT, administered
      separately, induced Mn while PHE showed no genotoxic effects. Binary and ternary
      mixtures of two or three metabolites gave different results, causing considerable
      increase or decrease in Mn induction. HQ and PHE, in binary mixtures, as well as
      PHE and CAT, increased Mn synergistically, while HQ and CAT interacted
      negatively. The genotoxicity of ternary mixtures was mainly the consequence of
      two metabolites: HQ and CAT. The maximal effect obtained is far below the
      induction of Mn consequent to benzene treatment. These data suggest that toxic
      and genotoxic effects of benzene alone could be the result of more complex
      interactions among these and other metabolites.

PMID- 7523943
TI  - Substituent effects on the genotoxicity of 4-nitrostilbene derivatives.
AB  - 4-Nitrostilbene and twelve of its derivatives (eleven E-stilbenes and two Z
      stilbenes) were examined for possible quantitative structure-activity
      relationships of their in vitro and in vivo genotoxicity. Relative mutagenicity
      was studied with and without S9 activation in Salmonella strains TA98 and TA100,
      as well as in the nitroreductase deficient strains TA98/NR and TA100/NR.
      Chromosomal aberrations in the bone-marrow cells of mice following
      intraperitoneal administration of the nitrostilbenes were observed as an
      indicator of in vivo genotoxicity. All of the compounds were active in TA98 and
      TA100 without S9 activation, with the exception of 4-amino-4'-nitrostilbene in
      TA100. Mutagenic activity was greatly reduced or eliminated in the NR strains,
      which is consistent with metabolic activation of the compounds by bacterial
      reductase. The presence of S9 lowered the activity of most of the nitrostilbenes
      presumedly by enzymatic detoxication. Hammet values of substituents, partition
      coefficients and frontier orbital energies (ELUMO and EHOMO) were studied for
      correlations with mutagenicity of the eleven E-stilbenes. Correlations could be
      established between mutagenicity in TA98 without S9 activation and the Hammet
      values. The same mutagenicity could also be correlated to ELUMO. Rationales for
      these correlations include the concept that electron-withdrawing groups which
      lower ELUMO should facilitate the reduction of the nitro group, leading to the
      proximate mutagen hydroxylamine. The correlations are also explained by the
      concept that electron-withdrawing groups should help stabilize the hydroxylamine
      intermediate and make the ultimate mutagenic species, the nitrenium ions, more
      reactive toward DNA. The relationship between mutagenicity and electronic effects
      of substituent groups found in vitro could not be extended to the in vivo
      results. However, except for the dinitrostilbenes, where insolubility prevented
      their testing, all the nitrostilbenes produced a statistically significant
      increase in chromosomal aberrations compared to the negative solvent control.

PMID- 7523944
TI  - Antimutagenicity of lemon grass (Cymbopogon citratus Stapf) to various known
      mutagens in salmonella mutation assay.
AB  - Lemon grass (Cymbopogon citratus Stapf) was extracted with 80% ethanol. The
      extract was not found to be mutagenic in the Salmonella mutation test with or
      without metabolic activation. However, the extract was found to possess
      antimutagenic properties towards chemical-induced mutation in Salmonella
      typhimurium strains TA98 and TA100. Mutagenicity of AFB1, Trp-P-1, Trp-P-2, Glu-P
      1, Glu-P-2, IQ, MNNG and AF-2, was inhibited by the extract of lemon grass in a
      dose-dependent manner, but no effect was found on the mutagenic activity of
      benzo[a]pyrene.

PMID- 7523946
TI  - A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in
      liver transplantation.
AB  - BACKGROUND: Tacrolimus (FK 506), a macrolide compound isolated from a bacterium,
      is a potent immunosuppressant with activity in solid-organ transplants. Most
      immunosuppressive regimens for liver transplantation are based on cyclosporine.
      METHODS: We conducted an open-label, randomized, multicenter trial to compare the
      efficacy and safety of tacrolimus-based and cyclosporine-based immunosuppressive
      regimens for patients receiving a first liver transplant. A total of 478 adults
      and 51 children (< or = 12 years of age) were randomly assigned at the time of
      transplantation to receive tacrolimus (n = 263) or cyclosporine (n = 266) and
      were followed for one year. The primary end points were patient and graft
      survival at one year. The secondary end points were the incidence of acute
      rejection, corticosteroid-resistant rejection, and refractory rejection
      (continued rejection after two courses of corticosteroids and an intervening
      course of muromonab-CD3). RESULTS: According to Kaplan-Meier analysis, actuarial
      patient-survival rates at day 360 were 88 percent for both the tacrolimus and
      cyclosporine groups (P = 0.85; 95 percent confidence interval for the difference,
      -5.4 to 6.6 percent), and graft-survival rates were 82 percent and 79 percent,
      respectively (P = 0.55; 95 percent confidence interval for the difference, -4.8
      to 9.7 percent). Acute rejection occurred in 154 patients in the tacrolimus group
      and 173 patients in the cyclosporine group (P < 0.002), corticosteroid-resistant
      rejection occurred in 43 and 82 patients, respectively (P < 0.001), and
      refractory rejection occurred in 6 and 32 patients, respectively (P < 0.001).
      Tacrolimus was associated with a higher incidence of adverse events requiring
      withdrawal from the study, primarily nephrotoxicity and neurotoxicity; 37
      patients in the tacrolimus group and 13 in the cyclosporine group discontinued
      the study because of adverse events (P < 0.001). CONCLUSIONS: After one year,
      immunosuppressive regimens based on tacrolimus and cyclosporine were comparable
      in terms of patient and graft survival. Tacrolimus was associated with
      significantly fewer episodes of acute, corticosteroid-resistant, or refractory
      rejection, but substantially more adverse events requiring discontinuation of the
      drug.

PMID- 7523945
TI  - Treatable gait disorder and polyneuropathy associated with high titer serum IgM
      binding to antigens that copurify with myelin-associated glycoprotein.
AB  - We studied clinical and electrodiagnostic features of 9 patients with very high
      titers (> 1:10,000) of serum IgM binding to a CNS myelin antigen (CMA)
      preparation that copurified with myelin-associated glycoprotein (MAG). We found
      that 8 of the 9 patients had a combined syndrome of gait ataxia and
      polyneuropathy (GAPN) with late-age onset (mean = 70 years of age). In the 8 GAPN
      patients progressive difficulty with ambulation led to significant functional
      disability and frequent falling. Examination showed a wide-based unsteady gait,
      especially when standing still or turning. There was mild-to-moderate distal
      sensory loss with involvement of joint position sense only in the toes. Motor
      changes, when present, were mild and mainly involved distal leg musculature.
      Treatment of 5 GAPN patients resulted in clear improvement of 2 after intravenous
      human immunoglobulin and of 3 others after other immunodulating agents. Immune
      mediated GAPN syndromes with high titers of serum IgM binding to CMA appear to be
      treatable causes of gait disorders in older patients.

PMID- 7523947
TI  - Immunosuppression in liver transplantation.

PMID- 7523948
TI  - Preventive health services.

PMID- 7523949
TI  - Brief report: diagnosis of Whipple's disease by molecular analysis of peripheral
      blood.

PMID- 7523951
TI  - A new class of ligand-gated ion channel defined by P2x receptor for extracellular
      ATP.
AB  - Extracellular ATP exerts its effects through P2 purinoceptors: these are ligand
      gated ion channels (P2x) or G-protein-coupled receptors (P2Y, P2U). ATP at P2x
      receptors mediates synaptic transmission between neurons and from neurons to
      smooth muscle, being responsible, for example, for sympathetic vasoconstriction
      in small arteries and arterioles. We have now cloned a complementary DNA encoding
      the P2x receptor from rat vas deferens and expressed it in Xenopus oocytes and
      mammalian cells. ATP activates a cation-selective ion channel with relatively
      high calcium permeability. Structural predictions suggest that the protein (399
      amino acids long) is mostly extracellular and contains only two transmembrane
      domains plus a pore-forming motif which resembles that of potassium channels. The
      P2x receptor thus defines a new family of ligand-gated ion channels.

PMID- 7523950
TI  - Secondary metabolites of Penicillium bilaii strain PB-50.
AB  - A phosphate-solubilizing strain of Penicillium bilaii was tested for the
      production of gliotoxin and other toxic compounds. The strain was fermented under
      five different conditions to allow the expression of various metabolites,
      including gliotoxin. These included Czapek-yeast extract medium under both shaken
      and still conditions as well as Czapek-yeast extract/malt extract/peptone medium
      and sucrose/glycerol medium in shake flasks. In addition, culture filtrate from
      an industrial fermentation of the fungus was examined. No gliotoxin was produced
      in any of the media. No other expected P. bilaii metabolites were found. Three
      compounds were identified in all samples: dibutyl phthalate, 1-(4-hydroxy
      phenyl)ethanone and 4-hydroxy-3,6-dimethyl-2H-pyran-2-one. The production of
      other metabolites was dependent on the culture conditions. Two hyalodendrin
      derivatives were found in some fermentations and two related compounds were
      tentatively identified. None of the compounds found have been reported as toxic.
      The identity of the culture was confirmed by comparison with the ex-type culture
      of P. bilaii.

PMID- 7523952
TI  - New structural motif for ligand-gated ion channels defined by an ionotropic ATP
      receptor.
AB  - The adenosine-5'-triphosphate (ATP) molecule is an extracellular messenger in
      neural and non-neural tissues, where it activates several cell-surface-receptor
      subtypes, including G-protein-coupled receptors and ligand-gated ion channels.
      ATP-gated channels (termed P2x receptors) have been characterized on smooth
      muscle cells and autonomic and sensory neurons, where they mediate membrane
      depolarization and, in some cases, Ca2+ entry. P2x receptors are functionally
      heterogeneous, but resemble acetylcholine- and serotonin-gated channels with
      respect to ion selectivity and kinetic parameters of channel gating. We report
      here that despite such close functional similarities, the deduced sequence of a
      cloned P2x receptor predicts an unusual subunit structure resembling voltage
      insensitive cation channels. Thus, the P2x receptor provides a striking example
      of convergent evolution, whereby proteins have been fashioned with similar
      functional properties from subunits having very different structural
      characteristics. There is sequence similarity between the ATP receptor and RP-2,
      a gene activated in thymocytes undergoing programmed cell death. RP-2 may encode
      a receptor for ATP or another metabolite released during apoptosis.

PMID- 7523954
TI  - Small-scale magnetic isolation of mRNA and synthesis of cDNA in 96-well plates.
AB  - Multiple small biological samples can be simultaneously prepared for RT-PCR by
      magnetically isolating mRNA and synthesizing cDNA in 96-well plates. The
      resulting accuracy, high throughput and ease of use facilitate commercial and
      clinical applications.

PMID- 7523953
TI  - Crystal structure of an RNA bacteriophage coat protein-operator complex.
AB  - The RNA bacteriophage MS2 is a convenient model system for the study of protein
      RNA interactions. The MS2 coat protein achieves control of two distinct processes
      -sequence-specific RNA encapsidation and repression of replicase translation--by
      binding to an RNA stem-loop structure of 19 nucleotides containing the initiation
      codon of the replicase gene. The binding of a coat protein dimer to this hairpin
      shuts off synthesis of the viral replicase, switching the viral replication cycle
      to virion assembly rather than continued replication. The operator fragment alone
      can trigger self-assembly of the phage capsid at low protein concentrations and a
      complex of about 90 RNA operator fragments per protein capsid has been described.
      We report here the crystal structure at 3.0 A resolution of a complex between
      recombinant MS2 capsids and the 19-nucleotide RNA fragment. It is the first
      example of a structure at this resolution for a sequence-specific protein-RNA
      complex apart from the transfer RNA synthetase complexes. The structure shows
      sequence-specific interactions between conserved residues on the protein and RNA
      bases essential for binding.

PMID- 7523955
TI  - Neurobiology. Inhibitory influences.

PMID- 7523958
TI  - [Developments in urology: current treatment methods in benign prostatic
      hypertrophy].

PMID- 7523956
TI  - Inefficient gene transfer by adenovirus vector to cystic fibrosis airway
      epithelia of mice and humans.
AB  - The success of adenoviral vectors for gene therapy of lung disease in cystic
      fibrosis (CF) depends on efficient transfer of the complementary DNA encoding the
      correct version of the cystic fibrosis transmembrane regulator (CFTR) to the
      affected columnar epithelial cells lining the airways of the lung. Pre-clinical
      studies in vitro suggest that low doses of adenovirus vectors carrying this CFTR
      cDNA can correct defective Cl- transport in cultured human CF airway epithelia.
      Here we use mice carrying the disrupted CF gene to test the efficacy of this
      transfer system in vivo. We find that even repeated high doses can only partially
      (50%) correct the CF defect in Cl- transport in vivo and do not correct the Na+
      transport defect at all. We investigated this discrepancy between the in vivo and
      in vitro transfer efficiency using CF mouse and human samples, and found that it
      reflects a difference in the susceptibility to adenovirus-5 transduction of the
      epithelial cell types dosed in vivo (columnar) and in vitro (basal-cell-like).
      These studies indicate that more efficient adenoviral gene-transfer vectors
      and/or refinement of dosing strategies are needed for therapy of CF lung disease.

PMID- 7523957
TI  - Inhibition of cyclosporin A/FK506 resistant, lymphokine-induced T-cell activation
      by phenothiazine derivatives.
AB  - Earlier studies from our laboratory have demonstrated that phenothiazine
      derivatives are capable of inhibiting mitogen-induced activation of human T-cells
      and thymocytes. Similar to cyclosporin A, phenothiazine derivatives exert these
      inhibitory effects by decreasing the accumulation of lymphokine-specific mRNA.
      However, proliferation of T-cell blasts and of unfractionated human thymocytes
      can also be induced by interleukin 2. Since activation of T-cells via the
      interleukin 2 receptor seems to be resistant to the action of cyclosporin A, the
      present study was designed to investigate whether lymphokine-induced activation
      could be inhibited by phenothiazine derivatives. The effects of the phenothiazine
      derivatives chlorpromazine and/or fluphenazine have been studied and compared to
      the action of cyclosporin A and FK506 in human thymocytes, human T-cell blasts
      and in the human T-cell line H33-HJ JA1, which is an interleukin 2 producing cell
      line derived from Jurkat cells. As evidenced by the incorporation of [3H]
      thymidine, cyclosporin A (1 microgram/ml) and FK506 (100 ng/ml) have no or only
      marginal inhibitory capacity on interleukin 2-induced proliferation in all T-cell
      systems tested. By contrast, phenothiazine derivatives (fluphenazine >
      chlorpromazine) exert a dose-dependent inhibition of the activation of these
      cells in pharmacologically relevant micromolar concentrations. Similar results
      were obtained by measuring the production of interferon-gamma in the supernatants
      of interleukin 2-induced human thymocytes. Our results suggest that the use of
      phenothiazines might be helpful in immunosuppressive regimens.

PMID- 7523959
TI  - [Urodynamic studies necessary for correct diagnosis in prostatism].

PMID- 7523960
TI  - [Laser prostatectomy as alternative to transurethral prostate resection in benign
      prostatic hyperplasia].
AB  - OBJECTIVE: Assessment of the results of laser prostatectomy, as a treatment for
      benign prostatic hyperplasia (BPH). DESIGN: Prospective case control study.
      SETTING: University Hospital Utrecht, the Netherlands. METHOD: Between February
      1992 and May 1993, 54 men with their micturition complaints due to BPH were
      treated with laser prostatectomy (TULIP system). Results were assessed using the
      international prostatic symptom score (IPSS), the maximal flow and urodynamic
      tests. The results were compared retrospectively with results of transurethral
      resection of the prostate (TURP; n = 40): both groups were urodynamically
      identical. RESULTS: Of the 54 patients, 10 could not be evaluated 6 months after
      treatment (5 of them underwent TURP or a second laser prostatectomy). In 40
      patients complete evaluation including urodynamics before and six months after
      treatment was possible. A significant decrease in the symptom score from 19.3
      (SD: 7.6) to 6.3 (SD: 5.4) and increase of the maximal flow during pressure-flow
      studies from 9.6 to 15.8 ml per second were observed. The decrease of the voiding
      pressure at 6 months after TURP in comparison with laser prostatectomy was close
      to significance (p = 0.05); the other improvements after urodynamics were
      comparable. CONCLUSION: Laser prostatectomy is a promising new therapy for BPH.

PMID- 7523961
TI  - [Transurethral microwave-thermotherapy in the treatment of benign prostatic
      hyperplasia].
AB  - OBJECTIVE: Determining the therapeutic efficacy of transurethral microwave
      thermotherapy (TUMT) in benign prostatic hyperplasia (BPH). DESIGN: Prospective.
      SETTING: Department of Urology, University Hospital Nijmegen, the Netherlands.
      METHOD: In the outpatient clinic, 130 BPH patients (mean age: 65.9 years (SD:
      6.9); mean prostatic volume 50.2 cm3 (SD: 18.4)) received TUMT in a single
      session lasting 60 min. The prostate was heated to above 45 degrees C by a
      microwave antenna in a urethral catheter, resulting in tissue necrosis. In the
      first year after treatment the Madsen symptom score, maximal flow, residual
      volume, prostatic volume and concentration of prostate-specific antigen in blood
      were collected. RESULTS: After 1 year 98 patients could be evaluated; of the
      other 32, 16 withdrew from follow-up, 10 underwent transurethral prostate
      resection and 6, other treatment. The maximal flow increased by 1.2 ml/s (SD:
      4.0). The residual volume decreased by 15.8 ml (SD: 55.6). Symptom scores
      improved by 5.9 points (SD: 5.0). A 50% increase in symptom score was seen in
      49.5% of all patients; 24.3% showed no improvement of complaints. There was no
      change in prostatic volume, whereas PSA concentration showed a transient increase
      in the first week after TUMT. Preliminary results after 6 months' follow-up of a
      randomised placebo-controlled study in 50 patients showed subjective and
      objective improvement of miction. CONCLUSION: TUMT results in distinct subjective
      improvement. Urodynamic findings show a less pronounced improvement.

PMID- 7523962
TI  - Palliative treatment of esophagogastric cancer by laser photocoagulation.
AB  - Over a 7-year period 158 nonsurgical patients with an advanced esophageal cancer
      were treated by palliation. The initial success rate was 79% and the
      complications rate was 2.3%. Average improvement duration was 136 days. Tumors
      were mostly situated in lower and middle part of oesophagus.

PMID- 7523963
TI  - [Prognostic factors in the surgery for intracranial meningioma. Role of the
      tumoral size and arterial vascularization originating from the pia mater. Study
      of 150 cases].
AB  - The authors report a series of 150 consecutive patients operated on for an
      intracranial meningioma over a period of 14 years (1974-1988). The patients were
      aged from 15 to 85 years (mean: 58 y; 49 were over 60 y) and severely disabled
      preoperatively in 42 cases (Karnofsky score 10 to 60). Tumors were located in the
      convexity in 22% the parasagittal region and falx in 24%, the skull base in 14%
      and the posterior fossa in 13%. In 21 cases the diameter of the tumor was less
      than 3 cm, in 86 it ranged from 3 to 6 cm, and in 43 cases it was more than 6 cm
      (29%). Tumor was hypervascularized in 51% of cases. Peritumoral edema was present
      in 73 of the 106 patients studied (69%). The tumor was removed completely (grade
      I and II of Simpson classification) in 136 cases (91%). Post-operative mortality
      was 10%. 88.5% of the surviving patients had a normal life with a score of 80 to
      100 according to Karnofsky scale. Recurrence rate amounted at 3.3%. Mortality and
      severe morbidity (poor outcome) were assessed and correlated with sex, age,
      tumor, size, location, vascularization, peritumoral edema and histology. From
      this retrospective study the only predictives of a poor outcome, statistically
      significant, were: severe preoperative neurological conditions (p < 0.001) and
      tumor size (p < 0.01). There was no statistically significant correlation with
      the other parameters. Cortical arteries participation to tumor vascularization,
      in a equal part of more than the dural arteries, led to subpial dissection for
      achieving complete tumor removal. This was a source of hemorrhagic infarction
      through ischemia, with patent neurological deficits for rolandic meningiomas (p =
      0.001). The importance of pial supply of the tumor was correlated with its size
      (p < 0.001). Pial supply of the tumour and consequently subpial dissection were
      foreseeable in the preoperative study: on selective angiography (p < 0.001) and
      the presence of peritumoral edema on CT scan (p < 0.001). The authors conclude
      that besides the "classic" pronostic factors (preoperative neurological
      conditions, tumor size), the mode of vascularization of the tumor (pial supply)
      plays an important role in the possibility or not to find an extra pial plan of
      dissection from the adjacent parenchyma, and consequently in the neurological
      outcome of the patients.

PMID- 7523964
TI  - Retroviral transfer of herpes simplex thymidine kinase gene into glioma cells
      causes targeting of gancyclovir cytotoxic effect.
AB  - The thymidine kinase (tk) gene of herpes simplex virus type 1 (HSV-1) was
      transduced into three glioma cell lines (T98, U251MG, T9) using a retrovirus
      vector. The supernatants of viral producer cell line PA317/LTRNL was used for
      infection and three transduced cell lines (T98/LTRNL, U251MG/LTRNL, T9/LTRNL)
      were established. The toxicities of the anti-herpetic drugs, acyclovir and
      gancyclovir, were evaluated in vitro. The cytotoxicities of acyclovir and
      gancyclovir to the HSV-1 tk gene-transduced cells increased 100-1000 fold
      compared to the non-transduced parental cell lines. The cytotoxic effect of
      gancyclovir was higher than that of acyclovir, requiring a concentration of less
      than 0.31 microM to obtain 50% inhibition. Deoxyribonucleic acid analysis of the
      gancyclovir-treated cells demonstrated fragmentation, suggesting that apoptosis
      is involved in the mechanism of cell death. The HSV-1 tk gene-transduced cells
      were co-cultured with parental cells and treated with gancyclovir. More than 95%
      of cells were killed in a mixture ratio of 1:1, suggesting that the "bystander
      effect" operated in this system. Selective transduction of HSV-1 tk gene into
      glioma cells using a retroviral vector and treatment with gancyclovir is a
      promising therapy for patients with malignant glioma.

PMID- 7523965
TI  - Relationship of cerebral blood flow, cerebral metabolism, and
      electroencephalography to outcome in acute experimental compression ischemia-
      barbiturate effects on delayed brain swelling.
AB  - Acute compression ischemia was induced in 30 cats by progressive inflation of an
      epidural balloon, followed by rapid decompression. Changes in intracranial
      pressure, mean arterial blood pressure, cerebral blood flow (CBF), arteriovenous
      oxygen difference (AVDO2), cerebral metabolic rate of oxygen (CMRO2), and
      electroencephalography (EEG) were studied in 13 untreated animals and in seven
      animals receiving barbiturate. Ten cats with cardiovascular or respiratory
      problems, or intracranial hematoma were excluded from the study. In untreated
      animals, six (46%) survived with no brain swelling and were classified as the "no
      swelling group," and seven (56%) died from fatal brain swelling and were
      classified as the "delayed swelling group." All animals with barbiturate therapy
      showed no brain swelling. Serial measurement of CBF, AVDO2, and CMRO2 indicated
      the existence of postischemic delayed hypoperfusion associated with relative
      hypermetabolism in untreated animals. Good recovery of CBF and CMRO2 was observed
      in the "no swelling group," and poor recovery in the "delayed swelling group."
      The time course of the total fast-wave components on EEG was quite similar to
      that of CMRO2, and the time course of the "CBF index," which is % fast-wave
      component of EEG divided by AVDO2, was similar to that of CBF. Barbiturates
      reduced CMRO2 and fast-wave component during administration, possibly improving
      the relatively hypermetabolic state, and reduced the mortality rate to 0%. The
      maximum effects of barbiturate could be expected by administering the drug at the
      stage of delayed hypoperfusion with relative hypermetabolism, indicated by rapid
      recovery of the % fast-wave component, high AVDO2, and low CBF index.

PMID- 7523966
TI  - Usefulness of non-detachable balloons in endovascular treatment for cerebral
      aneurysms.
AB  - An endovascular non-detachable balloon technique was used to treat 14 patients
      with cerebral aneurysms. Eight patients presented with subarachnoid hemorrhage,
      and six others presented with headache or mass effect. Six aneurysms were located
      in the anterior circulation and eight in the posterior circulation. Seven
      aneurysms were giant, three were large, and four were small. All target aneurysms
      or vessels were occluded successfully. Parent vessel was successfully spared in
      seven cases. There were no procedural complications related to the non-detachable
      nature of the balloon used. Follow-up angiography detected refilling of aneurysms
      in three of 11 patients, two with small ruptured aneurysms that bled again
      following partial deflation or balloon movement. The other aneurysms tested
      remained occluded, as demonstrated on follow-up angiograms, for up to 15 months.
      Outcomes were good to excellent in 10 patients, poor in one, and three died. Non
      detachable balloons might be preferred for treatment of certain types of cerebral
      aneurysms including those where intraaneurysmal maneuvers might be considered
      dangerous, for example, with recent bleeding or intraluminal fresh clots; where
      precise placement of the balloon is required, for example, in the vicinity of
      perforators or collaterals emerging near the neck; and where detachment could be
      dangerous or difficult in broad neck and fusiform aneurysms or in tortuous parent
      vessels.

PMID- 7523967
TI  - "Kissing aneurysms" of the internal carotid artery.
AB  - Five patients with kissing aneurysms (adherent internal carotid-posterior
      communicating artery and ipsilateral internal carotid-anterior choroidal artery
      aneurysms) are reported. There was female predominance and the subarachnoid
      hemorrhage was commonly due to rupture of the proximal posterior communicating
      artery aneurysm. Despite the demonstration of angiographic cleavage, the two
      aneurysms adhere to each other, which makes surgical dissection difficult.
      Meticulous dissection of the aneurysmal necks and preservation of the blood flow
      in the anterior choroidal artery are of vital importance.

PMID- 7523968
TI  - Evaluation of the patency of an extracranial-intracranial bypass using magnetic
      resonance angiography with selective presaturation of bypass vessels.
AB  - Three-dimensional time-of-flight magnetic resonance (MR) angiography using
      radiofrequency presaturation pulses was used to evaluate the patency of
      extracranial-intracranial (EC/IC) bypass in 11 patients. Presaturation causes
      signal loss in the vascular territory supplied by the presaturated EC/IC bypass
      graft. In all patients with a patent EC/IC bypass graft confirmed on conventional
      angiography, disappearance of the signal of the middle cerebral artery receiving
      blood flow from the bypass graft was clearly observed on MR angiograms with
      presaturation, indicating patency of the EC/IC bypass graft. MR angiography with
      presaturation pulses is a noninvasive and repeatable method for evaluation of the
      function of an EC/IC bypass graft.

PMID- 7523969
TI  - Percutaneous transluminal angioplasty of stenotic primitive hypoglossal artery-
      case report.
AB  - A 76-year-old female presented with vertebrobasilar insufficiency due to a severe
      stenosis of the right primitive hypoglossal artery (an unusual carotid-basilar
      anastomosis) manifesting as recurrent transient ischemic attacks (TIA) associated
      with quadriparesis and cerebellar ataxia with vertigo, nausea, and vomiting. She
      had been treated with 100 mg of aspirin per day, but TIA associated with the same
      symptoms persisted. Cerebral blood flow (CBF) studies disclosed a region of
      moderately low flow in the posterior fossa. Cerebral angiography demonstrated
      that the posterior fossa was supplied via the right primitive hypoglossal artery,
      which was severely stenotic at its origin. Percutaneous transluminal angioplasty
      using a Stealth catheter, 3.0-mm diameter and 10-mm long, successfully dilated
      the stenosis. No TIA occurred postoperatively, and a marked increase in CBF was
      demonstrated in the posterior fossa.

PMID- 7523970
TI  - Medulloblastoma associated with cysts and calcifications--case report.
AB  - An 11-year-old boy presented with medulloblastoma occurring in the cerebellar
      vermis. Computed tomography and magnetic resonance imaging revealed numerous
      cysts and calcifications in the tumor. The tumor was subtotally removed and
      cellular synchronization radiation therapy given. He was discharged without
      neurological deficits. Histological examination showed the cysts represented
      necrotic foci. Macrophages, which appeared around the necrotic foci, were
      important in the development of the calcifications via proliferation of collagen
      fibers.

PMID- 7523971
TI  - Extradural extension of primitive neuroectodermal tumor--case report.
AB  - A 13-year-old boy presented with a primitive neuroectodermal tumor (PNET) with
      unusual extracranial extension. Precontrast computed tomography showed the tumor
      as a ring-shaped high-density area which was enhanced postcontrast, with a low
      density center. Magnetic resonance imaging showed the tumor as a low-intensity
      area on the T1-weighted images with marked enhancement by gadolinium
      diethylenetriaminepentaacetic acid, and high intensity on the T2-weighted images.
      The central area appeared as high intensity on both images, suggesting free
      methemoglobin. The tumor was subtotally removed. Histological examination
      demonstrated PNET. Despite irradiation (20 Gy) to the surgical site, and further
      tumor removal, he died 6 months later. This case showed PNET can extend
      extracranially. Diagnosis and treatment of such a tumor located extracranially
      and intracranially require careful consideration.

PMID- 7523972
TI  - Acute purulent discitis with epidural abscess of the cervical spine in an adult-
      case report.
AB  - A 52-year-old male presented with acute purulent discitis and epidural abscess of
      the cervical spine manifesting as neck pain and slight fever, followed by sudden
      onset of quadriparesis. Magnetic resonance (MR) imaging showed a low-signal
      intensity area in the C6/7 disc space and epidural space ventral to the spinal
      cord with peripheral enhancement. Surgical exploration using an anterior approach
      revealed local discitis and epidural abscess, but no osteomyelitis of the
      neighboring vertebral bodies. Six months after the decompressive procedure to
      treat the purulent disc and epidural abscess, he had achieved almost full
      recovery. Such lesions are rare in adults, but should be considered especially
      when painful spinal symptoms are associated with fever. Early and definitive
      diagnosis can be achieved by MR imaging with enhancement.

PMID- 7523973
TI  - Evolution of chronic subdural hematoma after burr-hole exploration for subdural
      effusion--case report.
AB  - A 57-year-old male developed subdural effusion after head trauma, which remained
      asymptomatic and unchanged in volume during a follow-up period of 3 months. A
      typical chronic subdural hematoma (CSDH) developed 6 weeks after burr-hole
      exploration in spite of the absence of hematoma capsule or blood components in
      the effusion. The CSDH was successfully treated by irrigation and drainage. This
      case suggests that the presence of blood in subdural effusion may be the trigger
      for evolution of CSDH. We recommend that asymptomatic subdural effusion should be
      followed up without surgical intervention.

PMID- 7523975
TI  - Immersion and perfusion staining with 2,3,5-triphenyltetrazolium chloride (TTC)
      compared to mitochondrial enzymes 6 hours after MCA-occlusion in primates.
AB  - 2,3,5-triphenyltetrazolium chloride (TTC) is commonly applied in rodents and cats
      as a marker of infarcted tissue as early as 20 min after the onset of focal
      ischaemia. At this stage it is suggested that it reflects hypoperfusion rather
      than failure of respiratory chain. Immersion of brain slices in TTC solution is
      preferable in comparison to perfusion with TTC in order to ensure, that enough
      TTC enters the post-occlusion tissue. We compared immersion technique versus
      perfusion technique 6 h after permanent occlusion of the left middle cerebral
      artery in 18 baboons. In addition, we assessed the function of the respiratory
      chain enzymes of stained and unstained tissue in three baboons. The immersion
      technique revealed an absence of TTC staining limited to subcortical structures
      in two animals. In seven experiments TTC indicated involvement of almost the
      entire MCA territory. The extent of the ischaemic lesion indicated by the
      perfusion technique was very similar. Tissue samples from the presumed infarcted
      areas revealed normal mitochondrial function. We conclude that perfusion and
      immersion technique do not cause significant different ischaemic delineation 6 h
      after middle cerebral artery occlusion. TTC staining appears to be a reliable
      method of evaluating volume of infarction in primates. Furthermore, absence of
      TTC staining 6 h after stroke onset is caused by energy or oxygen depletion
      rather than by mitochondrial injury.

PMID- 7523974
TI  - Ubiquitin and neurofilament expression in anterior horn cells in amyotrophic
      lateral sclerosis: possible clues to the pathogenesis.
AB  - Cytoskeletal abnormalities are a prominent pathological feature of anterior horn
      cells in amyotrophic lateral sclerosis (ALS), and are thought to be involved in
      the process of motor neuron death. Skein-like filamentous inclusions have been
      detected by immunocytochemical staining for ubiquitin, a stress protein involved
      in targeting abnormal proteins for proteolysis. So far, identification of the
      target protein has been elusive. We have studied the ultrastructural localization
      of ubiquitin and neurofilaments by post-embedding immunogold staining. In skein
      like arrays, strong ubiquitin labelling was concentrated on abnormally formed 15
      20 nm filaments; neurofilament labelling was localized on 10 nm filaments
      adjacent or in continuity with the abnormal filaments. In addition, Bunina bodies
      were a major site of ubiquitin accumulation. Our results suggest that
      ubiquitinated filaments in skein-like inclusions might originate from abnormally
      aggregated neurofilament proteins, which are no longer recognized by antibodies
      to neurofilament epitopes. Furthermore, the presence of ubiquitin in Bunina
      bodies suggests that, in addition to its protective role, ubiquitin might be
      directly implicated in the mechanism of programmed neuronal death in ALS.

PMID- 7523977
TI  - Comparative patch clamp studies on the kinetics and selectivity of glutamate
      receptor antagonism by 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline
      (NBQX) and 1-(4-amino-phenyl)-4-methyl-7,8-methyl-endioxyl-5H-2,3-benzodiaze pine
      (GYKI 52466).
AB  - The glutamate antagonistic effects of NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo(F)quinoxaline] and GYKI 52466 [1-(4-amino-phenyl)-4-methyl-7,8-methyl
      endioxyl-5H-2,3-benzodiaze pine] were compared on inward current responses of
      cultured superior collicular and hippocampal neurones with the whole cell patch
      clamp technique. Both NBQX (8 microM) and GYKI 52466 (33 microM) selectively
      reduced responses to AMPA [(S)-alpha-amino-3-hydroxy-5-methyl-4-
      isoxazolepropionic acid, 50 microM] and kainate (50 microM) whilst having little
      effect on responses to NMDA (N-methyl-D-aspartate, 100 microM). The effects of
      the two antagonists on the kinetics of AMPA (50 microM) responses were, however,
      very different--NBQX dramatically slowed the rise time of responses so that peak
      currents (IC50 60.4 +/- 4.2 nM) were markedly more effected than desensitized
      plateau currents (IC50 706 +/- 99 nM) whereas GYKI 52466 antagonized plateau
      responses (IC50 4.44 +/- 0.21 microM) somewhat more than peak responses (IC50
      6.87 +/- 0.46 microM) and had only marginal effects on kinetics. In fact, low
      concentrations of NBQX (50-250 nM) actually potentiated plateau AMPA responses-
      an effect likely to be due to a reduction in the degree of AMPA-induced
      desensitization. Similar effects on response kinetics, were seen with kainate
      such that the IC50s for NBQX in antagonizing initial and plateau components of
      current responses to kainate 400 microM were 18.1 +/- 2.9 nM and 298 +/- 27 nM
      respectively whereas the IC50s for GYKI 52466 against kainate 50 microM were 17.3
      +/- 1.8 microM and 15.5 +/- 3.3 microM respectively. These differences are likely
      to be due to the different modes of action of the two antagonists--NBQX shifted
      kainate concentration responses curves to the right in a parallel fashion
      indicative of competitive antagonism whereas the effects of GYKI 52466 were
      largely noncompetitive. There was, however, some indication for a small
      allosteric influence of GYKI 52466 on the affinity of the glutamate recognition
      site of the AMPA/kainate receptor. Estimation of Kbs using the Cheng-Prussoff
      relationship revealed little difference in the affinity of NBQX in antagonizing
      plateau responses to AMPA (Kb 23.2 nM) and kainate (Kb 57.1 nM) and indicate that
      the effects of these two agonists are mediated at a common receptor under the
      experimental conditions used. Moreover, the differential effects of NBQX on peak
      and plateau components of AMPA (50 microM) responses was associated with a
      desensitization-induced, paradoxical increase in the agonist affinity and was
      probably not due to any change in the affinity of NBQX.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 7523976
TI  - Preproenkephalin gene expression in the rat cerebral cortex during chronic
      tracheal stenosis.
AB  - To evaluate whether the endogenous opioid system is activated in the higher brain
      centre while a chronic resistance to airflow, we examined changes of mRNAs for
      preproenkephalin (PPE)-A, which is a precursor of enkephalin, and for 70 kD heat
      shock protein (HSP70) in the cerebral cortex of rat brain during chronic tracheal
      stenosis. Northern blot revealed that PPE-A mRNA was induced at 3 days of airway
      stenosis. In situ hybridization revealed that PPE-A mRNA was gradually induced in
      frontal cortex. The significant induction of PPE-A mRNA was observed at 3 and 7
      days. However, no significant induction of HSP70 gene was observed. These results
      suggest that the endogenous opioid system may be at work as an important
      compensatory mechanism to reduce the respiratory sensation during chronic
      respiratory stress.

PMID- 7523978
TI  - NK1 and NK2 receptors are similar in man and rabbit.
AB  - A series of 15-18 compounds that act on NK1 or NK2 receptors as agonists or
      antagonists have been tested in the monoreceptor systems of the rabbit vena cava
      (NK1) and the rabbit pulmonary artery (NK2) for biological activities and for
      their ability to displace [3H] [Sar9, Met(O2)11]SP or [125I] NKA respectively
      from NK1 or NK2 human binding sites obtained by transfection and functional
      expression of the cDNAs for these receptor subtypes in CHO-K1 cells. For the two
      tachykinin receptors studied, positive highly significant correlations have been
      shown between binding and biological assays. Slopes of correlations are linear
      and near unity (r = 0.918 and 0.938). For NK1 and NK2 receptors the pharmacology
      in human and rabbit tissues appears to be very similar. The assays of biological
      activity on rabbit tissues may be therefore used to complement binding studies on
      human transfected cells to identify new antagonists for human tachykinin
      receptors.

PMID- 7523980
TI  - Effect of a neurokinin-1 (NK1) receptor antagonist on oedema formation induced by
      tachykinins, carrageenin and an allergic response in guinea-pig skin.
AB  - The effect of the neurokinin-1 (NK1) receptor antagonist RP67580 in modulating
      inflammatory oedema formation has been investigated in guinea-pig skin. Oedema
      formation was measured over 30 min by the extravascular accumulation of
      intravenously-injected 125I-albumin in the anaesthetised guinea-pig. RP67580 was
      injected intradermally with the agents under test. Intradermal RP67580 (10
      nmol/site) inhibits oedema formation induced by substance P (30 pmol) and
      neurokinin A (100 pmol), but not that induced by bradykinin (10-1000 pmol) or
      histamine (10 nmol). Substance P-induced oedema formation is similar in control
      (saline) and mepyramine (histamine H1 receptor antagonist) pretreated guinea-pigs
      suggesting a minimal involvement of histamine in substance P induced oedema
      formation in guinea-pig skin. Oedema formation induced by intradermal carrageenin
      (0.2%) was not inhibited by RP67580 (1-10 nmol). A significant but partial
      inhibition of oedema formation induced in a passive cutaneous anaphylaxis (PCA)
      response was observed. The oedema formation in the PCA was inhibited 50% by
      mepyramine pretreatment but in the presence of mepyramine no further inhibition
      of the PCA response by RP67580 was observed.

PMID- 7523981
TI  - Evidence for localized release of substance P within rat spinal cord evoked by
      physiological and electrical stimuli.
AB  - Antibodies immobilized onto the outer surface of glass microelectrodes were used
      to measure and localize substance P (SP) release in the spinal cords of
      anaesthetized rats. Utilizing a C-terminally directed antibody, significant
      levels of SP were not found in the lumbar spinal cord in the absence of
      peripheral noxious stimulation. Following noxious heating or pinch of the
      ipsilateral hind paw or electrical stimulation of the ipsilateral tibial nerve at
      C-fibre strength, significant amounts of released SP were detected. This noxious
      stimulus-evoked release of SP was primarily in the region of the substantia
      gelatinosa. In conclusion, the antibody microprobe technique can be employed to
      focally detect the release of neuropeptide in vivo, even in structures as small
      as rat spinal cord. The technique reveals that SP release in the rat follows
      broadly the same pattern as that previously reported in the cat.

PMID- 7523982
TI  - Release of the nitric oxide precursor, arginine, from the thalamus upon sensory
      afferent stimulation, and its effect on thalamic neurons in vivo.
AB  - The neurophysiology and neuroanatomy of the thalamus have been extensively
      studied in a variety of species and sensory systems. The identity of the
      neurotransmitter(s) which mediate the excitation from ascending sensory afferents
      on to thalamic relay neurons is, however, still unclear, although it appears to
      be a substance which is a ligand for excitatory amino acid receptors, as the
      responses of ventrobasal thalamus neurons to natural stimulation of somatosensory
      afferents arising from the mustachial vibrissae of the rat are mediated by
      ionotropic excitatory amino acid receptors, when stimulation is performed using
      an air-jet directed at the vibrissa receptor field. In an effort to determine the
      transmitter of these sensory afferents, we have attempted to detect the release
      of amino acids in the ventrobasal thalamus in vivo upon such stimuli. We have
      thus used a similar natural stimulation protocol, together with push-pull
      perfusion and recording in the ventrobasal thalamus, and we describe the release
      of the amino acid, arginine, in this brain area following physiological
      stimulation of afferents. Furthermore, we show that application of L-arginine on
      to thalamic relay neurons can facilitate sensory synaptic transmission, possibly
      via the synthesis of the diffusable messenger, free radical gas, nitric oxide.
      This may represent a novel, local positive-feedback, modulatory system which
      could enhance the responsiveness of thalamic neurons to sensory input.

PMID- 7523979
TI  - The role of neuropeptides in the regulation of adrenal zona
      fasciculata/reticularis function. Effects of vasoactive intestinal polypeptide,
      substance P, neuropeptide Y, Met- and Leu-enkephalin and neurotensin on
      corticosterone secretion in the intact perfused rat adrenal gland in situ.
AB  - There is much evidence to suggest that glucocorticoid secretion may be influenced
      by the splanchnic innervation to the adrenal gland, and that this effect may be
      mediated by neuropeptides. The present studies investigated the effects of
      several neuropeptides on corticosterone secretion by the intact perfused rat
      adrenal gland in situ. Both vasoactive intestinal polypeptide and Met-enkephalin
      caused a dose-dependent increase in corticosterone secretion, with a maximum
      response of 450% and 370% increment in corticosterone respectively. Of the other
      peptides tested, Leu-enkephalin, substance P and neurotensin all stimulated
      corticosterone secretion, with a maximum response of around 160% increase in each
      case. Neuropeptide Y on the other hand, had only a minor effect, which was only
      apparent over a small dose range. These results support the theory that adrenal
      neuropeptides may have a role in the regulation of glucocorticoid secretion.

PMID- 7523983
TI  - Human striatum: chemoarchitecture of the caudate nucleus, putamen and ventral
      striatum in health and Alzheimer's disease.
AB  - The morphology and distribution of perikarya positive for choline
      acetyltransferase, somatostatin, calcium binding protein (calbindin D28K) and
      nicotinamide adenine dinucleotide phosphate diaphorase were surveyed in the human
      striatum. Choline acetyltransferase and somatostatin antibodies labeled separate
      populations of large striatal interneurons. Somatostatin immunoreactivity and
      nicotinamide adenine dinucleotide phosphate diaphorase (nitric oxide synthase)
      activity were completely co-localized. Calbindin antibody identified two distinct
      groups of striatal neurons: (1) numerous medium-sized, lightly stained neurons,
      probably analogous to striatopallidal projection neurons in the rat, and (2) much
      less numerous, large, darkly stained neurons. Half of the latter group, but none
      of the former, were also nicotinamide adenine dinucleotide phosphate diaphorase
      positive. Somatostatin-positive and medium-sized, calbindin-positive neurons were
      more numerous in the caudate nucleus than in the putamen or ventral striatum. By
      contrast, large calbindin-immunoreactive neurons were more frequently encountered
      in the putamen. Choline acetyltransferase-positive neurons were evenly
      distributed across striatal components. In aged control subjects, the size of
      large, darkly stained calbindin-positive neurons was reduced relative to young
      subjects. Aging had no effect on somatostatin-, medium-sized calbindin-, or
      choline acetyltransferase-positive neurons. However, in histologically confirmed
      cases of Alzheimer's disease, there was a selective, 75% loss of choline
      acetyltransferase-immunoreactive perikarya from the ventral striatum, but not
      from the dorsal striatum, compared to aged controls. Furthermore, the remaining
      cholinergic neurons in the ventral striatum of Alzheimer's disease cases were
      significantly smaller than similar neurons in controls. These results indicate
      that various striatal components which have been shown to differ in their
      anatomical connectivity and functional specialization, also differ in their
      neurochemical signatures. The specific and marked loss of choline
      acetyltransferase-positive neurons from the ventral striatum in Alzheimer's
      disease is consistent with the characteristic cholinergic and 'limbic' pathology
      in this disease.

PMID- 7523984
TI  - Basal forebrain cholinergic neurons are selectively vulnerable to AMPA/kainate
      receptor-mediated neurotoxicity.
AB  - We exposed murine basal forebrain neuronal cultures for 24 h to defined
      concentrations of N-methyl-D-aspartate, kainate or alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionate, and assessed the resultant degeneration of the cholinergic
      neuronal subpopulation, as identified by choline acetyltransferase
      immunocytochemistry and acetylcholinesterase histochemistry. Cholinergic neurons,
      representing about 0.5% of the total neuronal population, were atypically
      vulnerable to excitotoxins. Compared to most basal forebrain neurons, they were
      more vulnerable to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate
      receptor-mediated injury and slightly less vulnerable to N-methyl-D-aspartate
      receptor-mediated injury. The present findings provide quantitative demonstration
      of a mechanism that preferentially injures basal forebrain cholinergic neurons,
      and may thus suggest candidate factors pertaining to their loss in disease states
      like Alzheimer's disease.

PMID- 7523985
TI  - Projections of nitric oxide synthase-containing fibers from the sphenopalatine
      ganglion to cerebral arteries in the rat.
AB  - The origin and distribution of cerebral perivascular nerves containing nitric
      oxide, a short-acting messenger or neurotransmitter, have been studied in the rat
      by histochemistry for reduced nicotinamide adenine dinucleotide phosphate
      diaphorase activity, a specific marker for neuronal nitric oxide synthase.
      Positively stained nerve fibers were distributed throughout the major vessels of
      the cerebral arteries, though the fiber density was higher in the anterior
      circulation, including the circle of Willis, than in the posterior arteries.
      Examination using axonal transport methods indicated that nitric oxide-containing
      neurons in the sphenopalatine ganglion innervate the cerebral arteries
      bilaterally. Nitric oxide synthase in these ganglionic cells often co-existed
      with vasoactive intestinal polypeptide. The anatomical information obtained is
      discussed in terms of non-adrenergic, non-cholinergic neuronal transmission in
      the cerebral arteries.

PMID- 7523986
TI  - Commissural connections of the cat periaqueductal gray matter studied with
      anterograde and retrograde tract-tracing techniques.
AB  - The commissural connections of the periaqueductal gray matter were investigated
      by light and electron microscopy by using the anterograde tracer Phaseolus
      vulgaris leucoagglutinin and the retrograde tracer horseradish peroxidase. In the
      first group of seven animals (1-7), single injections of Phaseolus vulgaris
      leucoagglutinin were performed iontophoretically (4.5 microA for 30 min) into
      various subdivisions of the periaqueductal gray matter. On light microscopic
      examination, injection sites were characterized by several immunolabeled neurons
      of different sizes and morphology, with the cytoplasm, nucleus and neuronal
      processes intensely stained. Many labeled fibers turned from injection sites
      toward all contralateral periaqueductal gray matter subdivisions, but anterograde
      labeling was densest in the regions homotopic to those injected. Commissural
      fibers bore along their course many en passant boutons of different sizes and
      morphology, and gave off spine-like processes, at the end of which one terminal
      bouton was observed. Labeled fibers branched into numerous collaterals which
      ended in a terminal array of 10-20 en passant and en grappe boutons. At the
      electron microscopic level, commissural axons were observed in close proximity to
      the cytoplasmic membranes of cells. Axon terminals formed symmetric or asymmetric
      synapses mainly on dendritic shafts of neurons and rarely on vesicle-containing
      profiles. Horseradish peroxidase experiments were carried out in four cats (1-4).
      The tracer was injected iontophoretically into different regions of the
      periaqueductal gray matter of three cats (1-3). Retrogradely labeled neurons
      giving rise to commissural connections had a morphology similar to that of
      polygonal, triangular and fusiform cells described in previous Golgi studies. The
      perikaryal cross-sectional area of commissural neurons was smaller than that of
      neurons projecting outside the periaqueductal gray matter (mean value of
      commissural neurons 149.77 microns 2 vs 261.19 microns 2 for projecting neurons),
      which were retrogradely labeled by pressure-injecting horseradish peroxidase into
      several targets of periaqueductal gray matter (4). Moreover, since the
      distribution of sizes of the two populations of the periaqueductal gray matter
      overlapped in the range of 90-300 microns 2, a considerable number of projecting
      neurons were as small as commissural neurons. The present results suggest that
      commissural fibers could reciprocally connect zones of the periaqueductal gray
      matter with similar functions, and originate from small and medium-sized neurons,
      some of which are also projecting neurons.

PMID- 7523987
TI  - Release of immunoreactive galanin in the spinal cord of rats with ankle
      inflammation: studies with antibody microprobes.
AB  - Antibody microprobes bearing antibodies to the carboxy-terminus of rat galanin
      were inserted into the spinal cords of anaesthetized normal rats and those in
      which ankle inflammation had been induced by the unilateral subcutaneous
      injection of Freund's adjuvant four to six days previously. In normal rats, a
      basal presence of immunoreactive galanin was detected in the dorsal horn. Similar
      levels of immunoreactive galanin were found in the dorsal horn of both sides of
      the spinal cord in animals with unilateral ankle inflammation. Flexing the ankle
      or compressing the foot in normal rats failed to alter levels of immunoreactive
      galanin detected by microprobes. In animals with ankle inflammation, prolonged
      periods of ankle flexion did release immunoreactive galanin in the ipsilateral
      dorsal horn. Subsequent noxious ankle compression in these animals did not
      increase but rather decreased immunoreactive galanin in the dorsal horn to below
      basal levels. The reason for this decrease is unknown but it may represent an
      inhibition of release or a depletion of spinal stores of galanin.

PMID- 7523988
TI  - Chronic intrastriatal quinolinic acid produces reversible changes in perikaryal
      calbindin and parvalbumin immunoreactivity.
AB  - We recently reported the use of a chronic dialytic delivery system for
      intrastriatal administration of quinolinic acid in the rat. This system produces
      neurodegeneration with some characteristics similar to post mortem brain tissue
      from Huntington's disease patients, including reduced cytochrome oxidase
      staining, a decreased number of Nissl-stained neurons, and relative sparing of
      striatal NADPH-diaphorase containing neurons. The present findings show that
      chronic dialytic delivery of quinolinic acid also produces a Huntington's disease
      like pattern of reduced calbindin and parvalbumin perikaryal immunoreactivity
      that is reversed in rats allowed four to eight weeks' recovery after cessation of
      quinolinic acid. Furthermore, cytochrome oxidase staining and the number of Nissl
      stained cells were unchanged in the region of transient calbindin and parvalbumin
      immunoreactive perikaryal staining alterations. These results suggest that
      changes in calbindin and parvalbumin perikaryal immunoreactivity provide a
      relatively sensitive measure of quinolinic acid induced neurotoxicity. The
      reversible nature of reduced perikaryal immunoreactivity suggests a premorbid
      state of neurotoxicity, possibly marked by cellular redistribution of calbindin
      and parvalbumin.

PMID- 7523989
TI  - Temporal dissociation between changes in striatal enkephalin and substance P
      messenger RNAs following striatal dopamine depletion.
AB  - Changes in the levels of enkephalin and substance P messenger RNA expression were
      examined in the striatum following dopamine depletion resulting from unilateral
      injection of 6-hydroxydopamine into the substantia nigra. In response to striatal
      dopamine depletion, the levels of enkephalin messenger RNA were elevated, whereas
      substance P messenger RNA was decreased within all regions of the striatum.
      Examination of the striatal peptide messenger RNAs between one and 21 days after
      the injection of 6-hydroxydopamine revealed a temporal dissociation between
      changes in enkephalin and substance P messenger RNAs. Within one day of the 6
      hydroxydopamine injection, substance P messenger RNA was significantly decreased
      by 30% at all levels of the striatum. This decrease was maintained for up to 21
      days after the lesion. In contrast, striatal enkephalin messenger RNA was not
      significantly elevated until three days following the injection of 6
      hydroxydopamine, after which there was a gradual increase up to 21 days. In order
      to correlate alterations in peptide messenger RNA expression with 6
      hydroxydopamine-induced changes in striatal dopamine innervation, tissue punches
      from the striatum were examined for dopamine content at one, two, three and seven
      days after the lesion. One day after the lesion, striatal dopamine levels were
      significantly increased by 47%. In contrast, within two days tissue dopamine
      content was reduced by 77% compared to control levels. A further decrease of 90%
      or more was observed at three and seven days after the lesion. Taken together,
      these data demonstrate a temporal dissociation between changes in enkephalin and
      substance P messenger RNA levels following 6-hydroxydopamine-induced striatal
      dopamine depletions. This temporal dissociation may reflect a differential
      response of enkephalin and substance P messenger RNAs to alterations in dopamine
      release and subsequent receptor activation.

PMID- 7523992
TI  - [The demonstration of seminal fluid stains on paper. II. The treatment of
      laboratory studies dealing with rape].
AB  - The authors suggest the use of Baecchi's staining for the morphological
      demonstration of spermatozoa on paper tissues. They affirm that the method
      suggested allows good results to be obtained even using material abandoned at the
      site of sexual aggression.

PMID- 7523991
TI  - Developmental aspects of suicidal behavior in children and developmentally
      delayed adolescents.

PMID- 7523990
TI  - Neocortical grafts receive functional afferents from the same neurons of the
      thalamus which have innervated the visual cortex replaced by the graft in adult
      rats.
AB  - Electrophysiological and anatomical studies were carried out in parallel to
      investigate the ability of lateral geniculate body neurons to regenerate axons
      damaged by the removal of the primary visual cortex and to innervate graft
      neurons functionally after transplantation of fetal neocortical tissue to a
      lesion cavity in the brain of adult rats. In electrophysiological experiments
      neurons of a large portion of the transplants (14/35) displayed visual responses
      with characteristics resembling closely those of normal primary visual cortex;
      these transplants also displayed a different degree of restoration of
      topographically organized visual field representations on them. To demonstrate
      anatomical regeneration of inputs from the host lateral geniculate body to the
      graft, injections of FluoroGold were made before grafting into the intact visual
      cortex for retrograde labeling of the lateral geniculate body neurons. After
      completion of the microelectrode recordings from the transplants a second dye,
      Bisbenzimide, was injected into the transplants. The rats with transplants whose
      neurons displayed responses to visual stimulations contained in the lateral
      geniculate body neurons with FluoroGold-labeled cytoplasm and Bisbenzimide
      labeled nuclei. The presence of double-labeled neurons suggests that the same
      neurons, the axons of which have terminated in area 17 of the cortex, innervated
      the transplants functionally through the regeneration of damaged axons.

PMID- 7523993
TI  - Short-term treatments with haloperidol or bromocriptine do not alter the density
      of the monoamine vesicular transporter in the substantia nigra.
AB  - [3H]dihydrotetrabenazine ([3H]TBZOH) was used to label the monoamine vesicular
      transporter in the rat substantia nigra. An accumulation of neuronal vesicles in
      the substantia nigra pars compacta was observed after blockade of the fast axonal
      transport by a microinjection of colchicine (10 micrograms/2 microliters) into
      the medial forebrain bundle. This accumulation was measured after sustained 2-day
      pharmacological modifications of the central dopaminergic transmission. It was
      not modified after s.c. administration of either the direct dopamine (DA)
      receptor agonist bromocriptine (four injections of 4 or 6 mg/kg) or the DA
      receptor antagonist haloperidol (four injections of 0.5-1-1.5-2 mg/kg). Thus, it
      appears that these pharmacological modifications, imposed to the activity of the
      nigro-striatal dopaminergic system during 2 days, have no consequence on the rate
      of synthesis of its vesicles.

PMID- 7523994
TI  - Central inhibition of nitric oxide synthase attenuates water intake but does not
      alter enhanced glucose utilization in the hypothalamo-neurohypophysial system of
      dehydrated rats.
AB  - I.c.v. administration of a nitric oxide (NO) synthase inhibitor (NG-monomethyl-L
      arginine, NMMA, 500 micrograms/5 microliters) to conscious rats deprived of water
      for 24 h attenuated drinking and decreased glucose utilization in the subfornical
      organ and median preoptic nucleus. NMMA did not alter the enhanced glucose
      utilization in the hypothalamo-neurohypophysial system (HNS) of dehydrated rats,
      although it has been shown to increase, selectively, oxytocin (OT) secretion
      [18]. This suggests that NO may act in the neural lobe to inhibit OT secretion
      and promote the preferential release of vasopressin during dehydration. This
      effect is similar to the blockade of endogenous opiate receptors by naloxone.

PMID- 7523995
TI  - Inhibitory effects of beta-amyloid peptides on nicotine-induced Ca2+ influx in
      PC12h cells in culture.
AB  - Synthetic beta-amyloid peptides and the neuropeptide substance P (SP) were
      examined for their ability to modulate nicotinic response in PC12h cells, a
      subclone of PC12 cells, SP, beta A1-40 and its peptide fragment beta A25-35-NH2
      significantly inhibited an increase in cytoplasmic calcium concentrations
      ([Ca2+]i) induced by nicotine in a dose-dependent manner. Furthermore, beta A1-40
      was found to inhibit the [Ca2+]i increase induced by depolarization with a high
      concentration of potassium. These findings show that both beta A1-40 and beta A25
      35-NH2 may mimic the function of SP on inhibition of nicotinic response through
      different mechanisms.

PMID- 7523997
TI  - A behaviorally active dose of lipopolysaccharide increases sensory neuropeptides
      levels in mouse spinal cord.
AB  - To assess whether peripheral immune stimuli activate sensory afferents at
      behaviorally active doses, we measured the effects of lipopolysaccharide (LPS) on
      the levels of sensory neuropeptides in the spinal cord. LPS (10 micrograms/mouse
      i.p.) increased the levels of substance P, neurokinin A, and calcitonin gene
      related peptide in the spinal cord, the maximum being observed 1 hr post
      injection. Pretreatment with indomethacin at a dose (5 mg/kg i.p.) which
      completely blocked the decrease in food-motivated behavior induced by LPS
      abrogated this effect.

PMID- 7523996
TI  - Nitric oxide regulates spike frequency accommodation in nodose neurons of the
      rabbit.
AB  - A Ca(2+)-dependent slow spike after hyperpolarization (AHPslow) is present in
      about 35% of the neurons in the nodose ganglion. Although the AHPslow profoundly
      affects spike frequency accommodation of these neurons, the mechanisms that
      control the generation and the duration of the AHPslow are unclarified. N omega
      Nitro-L-arginine methyl ester (L-NAME; 10 microM), a specific inhibitor of nitric
      oxide synthase (NOS), reduced the AHPslow by more than 92%. The L-NAME block of
      the AHPslow was antagonized by application of 50 microM S-nitroso-N
      acetylpenicillamine (SNAP), a nitric oxide donor. The fast, Ca(2+)-dependent,
      spike after hyperpolarization preceding the AHPslow and the elevation of
      intracellular Ca2+ accompanying the AHPslow were unaffected by L-NAME treatment.
      These findings indicate that products of NOS activity might directly or
      indirectly activate the AHPslow K+ channels at a step beyond Ca2+ influx or
      intracellular Ca2+ mobilization.

PMID- 7523998
TI  - Inhibition of a 5-HT3 receptor-mediated current by the selective serotonin uptake
      inhibitor, fluoxetine.
AB  - The effect of the selective serotonin uptake inhibitor, fluoxetine, on the inward
      current mediated by 5-HT3 receptors was investigated with the whole-cell patch
      clamp technique. Fluoxetine inhibited the peak 5-HT current with an IC50 value of
      1.2 microM. During continuous application of fluoxetine at concentrations of < or
      = 1 microM, there was a transient decrease in the fluoxetine-induced inhibition
      of 5-HT current. It is suggested that fluoxetine may have a short-lived action on
      5-HT current and that the 5-HT3 receptor is a possible acting site for the
      therapeutic use of fluoxetine.

PMID- 7523999
TI  - Serotonin and NADPH-diaphorase in the dorsal raphe nucleus of the adult rat.
AB  - NADPH-diaphorase histochemistry, employed as a marker for nitric oxide synthase
      (NOS), was combined with serotonin (5-HT) immunofluorescence to investigate the
      relationship between NOS and 5-HT in the rat dorsal raphe nucleus. Many NADPH
      diaphorase labelled cells and varicose axons were observed in the nucleus.
      Coexistence between NADPH-diaphorase and 5-HT occurs in cells of the dorsomedial
      and ventromedial subgroups but not in the lateral subgroups. Coexistence was not
      observed in axons, but NADPH-diaphorase labelled axons contact 5-HT/NADPH
      diaphorase containing cell bodies. These findings have implications for the role
      of nitric oxide in 5-HT pathways and for the mechanism of action of 5-HT
      neurotoxins.

PMID- 7524000
TI  - Coexistence of galanin and substance P in the mouse nasal mucosa, including the
      vomeronasal organ.
AB  - Immunohistochemical fluorescent double labeling revealed the coexistence of
      galanin and substance P in nerve fibers in the mouse nasal mucosa. At the base of
      and in the epithelium, all galanin fibers also contained substance P, but around
      the blood vessels and glands, most of them did not. Since substance P fibers in
      the nasal mucosa originate from the trigeminal ganglion, these results suggest
      that galanin fibers in the submucosal region originate from ganglia other than
      the trigeminal.

PMID- 7524001
TI  - Immunocytochemical co-localization of substance P and calcitonin gene-related
      peptide in afferent renal nerve soma of the rat.
AB  - Substance P, calcitonin gene-related peptide and somatostatin immunoreactivities
      have been demonstrated in putative afferent renal nerve fibers in the rat.
      Utilizing retrograde-tracing and immunohistochemistry, we labeled afferent renal
      nerve soma throughout dorsal root ganglia T9 to L1. Most (85%) of afferent renal
      nerve perikarya were immunoreactive for calcitonin gene-related peptide, 21% had
      substance P immunoreactivity and none had somatostatin immunoreactivity. All
      renal afferents immunoreactive for substance P also contained calcitonin gene
      related peptide. These results provide evidence that calcitonin gene-related
      peptide and substance P are present and co-localized in afferent renal nerves,
      and therefore, mediate transmission of afferent renal input to the spinal cord in
      the rat.

PMID- 7524002
TI  - Association of serum beta-hCG levels with myosalpingeal invasion and viable
      trophoblast mass in tubal pregnancy.
AB  - OBJECTIVE: To test the hypothesis that myosalpingeal invasion and viable
      trophoblast mass are associated with serum beta-hCG levels in tubal-ampullary
      pregnancy. METHODS: Twenty-seven salpingectomy specimens of tubal-ampullary
      pregnancies were assessed for the presence or absence of myosalpingeal invasion.
      The mass of viable trophoblast was quantified in terms of the number of high
      power fields (x400) occupied. The cases were stratified into three groups: small,
      less than one field; medium, one or two fields; and large, more than two fields
      and/or embryo present. Beta-hCG was measured before the procedure (mIU/mL, Third
      International Standard). RESULTS: The mean (+/- standard error of the mean) beta
      hCG level for the nine cases exhibiting myosalpingeal invasion was significantly
      higher than for the 18 cases without invasion (13,665 +/- 2986 versus 2169 +/-
      870 mIU/mL; P = .0001). Beta-hCG levels greater than or equal to 5400 mIU/mL
      predicted myosalpingeal invasion in eight of nine cases (positive predictive
      value 89%). In contrast, levels less than 5400 mIU/mL were associated with lack
      of myosalpingeal invasion in 17 of 18 cases (negative predictive value 94%). The
      volume of trophoblast mass correlated with both beta-hCG levels (r = 0.647, P =
      .0003) and myosalpingeal invasion (r = 0.735, P = .0001). There was no invasion
      in the 13 cases in the group with small trophoblast mass, whereas two of five
      cases in the medium-mass group displayed myosalpingeal invasion. In this group,
      the mean beta-hCG for cases with myosalpingeal invasion was higher than in the
      cases without invasion (16,917 +/- 117 versus 3799 +/- 1094 mIU/mL; P = .003). In
      the group with large trophoblast mass, seven of nine specimens showed
      myosalpingeal invasion. CONCLUSION: Both myosalpingeal invasion and viable
      trophoblast mass correlate positively with serum levels of beta-hCG.
      Myosalpingeal invasion is highly likely when beta-hCG levels reach 5400 mIU/mL.

PMID- 7524004
TI  - Digital indocyanine-green videoangiography of occult choroidal
      neovascularization.
AB  - BACKGROUND: Occult choroidal neovascularization (CNV) secondary to age-related
      macular degeneration occurs in the majority of patients with exudative
      maculopathy. Since occult CNV cannot be imaged clearly by fluorescein
      angiography, this condition is untreatable. The authors performed digital
      indocyanine-green videoangiography (ICG-V) on 657 consecutive eyes with occult
      CNV by fluorescein angiography to determine if this technique could be useful in
      enhancing the imaging of the neovascularization, and thus increasing treatment
      eligibility. MATERIALS AND METHODS: Six hundred fifty-seven consecutive eyes with
      occult CNV were studied. The fluorescein and ICG angiograms were compared, and
      the percentage of patients potentially eligible for laser therapy based on ICG
      findings was calculated. RESULTS: Of 413 eyes with occult CNV without pigment
      epithelial detachments, focal areas of neovascularization were noted in 89 (22%).
      Overall, 142 (34.3%) eyes had lesions that were potentially treatable by laser
      photocoagulation based on additional information provided by ICG-V. Of the 235
      eyes with occult CNV and vascularized pigment epithelial detachments, 98 (42%)
      were eligible for laser therapy based on ICG-V findings. The authors calculate
      that ICG-V enhances the treatment eligibility by approximately one third.
      CONCLUSIONS: In diagnosing occult CNV, ICG-V is an important adjunctive technique
      to fluorescein angiography. This technique is especially useful in delineating
      occult neovascularization, neovascularization with overlying subretinal
      hemorrhage or serosanguineous fluid, and neovascularization associated with
      pigment epithelial detachments. The authors currently suggest that ICG-V be
      performed in eyes in which well-delineated neovascularization cannot be
      identified by fluorescein angiography. Based on their preliminary study, it can
      be expected that one in three patients with occult CNV potentially will be
      eligible for laser photocoagulation based on ICG-V. Further studies are necessary
      to confirm these findings.

PMID- 7524005
TI  - Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous
      carcinoma of the tongue.
AB  - A more accurate method of detecting nodal disease in squamous cell carcinoma of
      the tongue is needed so that treatment of the neck with its associated morbidity
      can safely be reserved for patients who actually have metastatic disease. Tumor
      angiogenesis and the expression of the p53 antigen--which have each been shown to
      be predictive of metastasis in breast and colon cancer, respectively--are
      examined for their ability to predict neck metastasis in tongue cancer. Fifty
      seven patients with T1 and T2 squamous cell carcinoma of the oral tongue, whose
      neck disease was examined by dissection or by 2-year follow-up, were studied.
      Twenty-eight patients (49%) were node positive and 29 patients (51%) were node
      negative. The primary tumors were immunohistochemically stained for the p53
      antigen and for factor VIII, which allowed the blood vessels within the tumor to
      be quantitated. The mean vessel counts per x200 high-power field were 59.8 and
      61.5 for node-positive and node-negative patients, respectively (p = 0.8). Node
      positive patients showed overexpression of p53 43% of the time, vs. 61% for node
      negative patients (p = 0.17). Multivariate analysis confirmed that no difference
      in tumor angiogenesis or the expression of the p53 antigen was found between
      tumors that had metastasized and those that had not. Therefore neither tumor
      angiogenesis nor the p53 tumor marker is clinically useful in determining lymph
      node metastasis in these patients.

PMID- 7524003
TI  - Second-trimester maternal serum alpha-fetoprotein, unconjugated estriol, and hCG
      levels in pregnancies with ventral wall defects.
AB  - OBJECTIVE: To determine if second-trimester maternal serum concentrations of
      unconjugated estriol (E3) and hCG are altered in pregnancies associated with
      fetal gastroschisis or omphalocele. METHODS: Concentrations of alpha-fetoprotein
      (AFP), unconjugated E3, and hCG were measured in a case-control study involving
      23 cases of gastroschisis, 17 cases of omphalocele, and 200 matched unaffected
      pregnancies. RESULTS: As reported previously, median AFP levels were
      significantly higher in pregnancies with gastroschisis and omphalocele compared
      to unaffected pregnancies (9.42 and 4.18 multiples of the unaffected population
      median [MoM], respectively). The median hCG values were not significantly
      different for the two defects (1.10 and 1.13 MoM, respectively). Six of the cases
      of omphalocele were associated with other anomalies, but exclusion of these cases
      from the analysis did not alter the conclusions. CONCLUSIONS: Unconjugated E3 and
      hCG measurements are not useful in screening for, or distinguishing between, open
      ventral wall defects. Alpha-fetoprotein measurements alone will detect nearly all
      cases of gastroschisis and most cases of omphalocele.

PMID- 7524006
TI  - Nitric oxide in the rat vestibular system.
AB  - Nitric oxide is known to function as a neurotransmitter in the central nervous
      system. It is also known to be involved in the central nervous system excitatory
      amino acid neurotransmission cascade. Activation of excitatory amino acid
      receptors causes an influx of calcium, which activates nitric oxide synthase. The
      resulting increase in intracellular nitric oxide activates soluble guanylate
      cyclase, leading to a rise in cyclic guanosine monophosphate. The excitatory
      amino acids glutamate and aspartate are found in the vestibular system and have
      been postulated to function as vestibular system neurotransmitters. Although
      nitric oxide has been investigated as a neurotransmitter in other tissues, no
      published studies have examined the role of nitric oxide in the vestibular
      system. Neuronal NADPH-diaphorase has been characterized as a nitric oxide
      synthase. This enzyme catalyzes the conversion of L-arginine to L-citrulline,
      producing nitric oxide during the reaction. We used a histochemical stain
      characterized by Hope et al. (Proc Natl Acad Sci 1991;88:2811) as specific for
      neuronal nitric oxide synthase to localize the enzyme in the rat vestibular
      system. An immunocytochemical stain was used to examine rat inner ear tissue for
      the presence of the enzyme's end product, L-citrulline, thereby demonstrating
      nitric oxide synthase activity. Staining of vestibular ganglion sections showed
      nitric oxide synthase presence and activity in ganglion cells and nerve fibers.
      These results indicate the presence of active nitric oxide synthase in these
      tissues and suggest modulation of vestibular neurotransmission by nitric oxide.

PMID- 7524007
TI  - Pseudomonas cepacia of the temporal bone: malignant external otitis in a patient
      with cystic fibrosis.

PMID- 7524008
TI  - Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P.
AB  - The hypothesis tested was that inhibition of the L-arginine-nitric oxide (NO)
      pathway may represent a potential central mechanism of action for acetaminophen
      (paracetamol). Spinal administration of N-methyl-D-aspartate (NMDA, 0.5 nmol),
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.1 nmol) or
      substance P (SP, 0.5 nmol) to the rat provoked a specific behaviour characterized
      by biting, scratching and licking (BSL). This behaviour was antagonized by
      pretreatment with acetaminophen for NMDA and SP but not for AMPA. Further, the
      antinociceptive effect of acetaminophen was readily reversed by administration of
      the natural substrate for nitric oxide synthase (NOS), L-arginine, but not by D
      arginine. This suggests that the analgesic effect of acetaminophen is related to
      inhibition of NO generation. Potential mechanisms for this may involve NMDA and
      SP. Our data suggest that a significant portion of the analgesic effect of
      acetaminophen, when used clinically, may be related to an interaction with the
      central nervous system L-arginine-NO pathway.

PMID- 7524009
TI  - Mothers' management of adenoid-tonsillectomy pain in 4- to 8-year-olds: a
      preliminary study.
AB  - The health care system has moved towards home care, early discharge, and day
      procedures. Parents in the home are, therefore, far more likely to be managing
      their children's postoperative pain than health professionals. The purpose of
      this study was to describe mothers' experiences in identifying and managing their
      children's acute pain associated with surgery. Because little is known about
      family's perceptions and management of a child's pain in the home, a qualitative
      design and grounded theory method were used. A purposive, convenience sample of 7
      mothers whose children were 4-8 years old and who had a day-surgery adenoid
      tonsillectomy were interviewed in depth (2-3 interviews per mother). Four themes
      were found in the data: (1) mothers' descriptions of their children's overall
      pattern of postoperative pain indicated that pain was minimal or absent before
      surgery, increased following surgery, and decreased with medicine and healing;
      (2) mothers' assessment and evaluation of their children's pain used pain cues
      similar to those used by nurses and physicians; (3) all the mothers worried about
      drug addiction; and 4) mothers learned to manage their children's pain through
      'trial and error'. This study provides beginning data for understanding family
      management of children's pain.

PMID- 7524010
TI  - Inflammation of the colonic wall induced by formalin as a model of acute visceral
      pain.
AB  - Acute inflammation of the sigmoid wall was induced by perendoscopic injection of
      formalin (50 microliters, 5%) under brief anesthesia in rats. The procedure was
      followed by behavioral patterns that significantly differed from those in animals
      injected with isotonic saline instead of formalin. Analysis of the formalin
      induced behaviors allowed for the calculation of a pain score that evolved in a
      biphasic manner along the 3 h of test. The score was dose-dependently reduced by
      morphine (0.5-4 mg/kg), and the analgesic effect of the largest morphine dose was
      abolished by naloxone (2.4 mg/kg). These results suggest that formalin into the
      sigmoid colon is a new model of visceral pain, presumably through direct
      irritation at injection site and/or localized acute inflammation of the
      intestinal wall.

PMID- 7524011
TI  - A theoretical rationale on the histogenesis of premalignant lesions and early
      carcinoma of the prostate.
AB  - Several localized non-malignant and dysplastic glandular proliferations of the
      prostate mimick well-differentiated invasive prostatic microcarcinoma (PMC).
      However, the basal cell layer (BCL) is intact and evident in benign hyperplasias
      and lacking in PMC; consequently, immunohistochemical reactions for BCL, by means
      of keratin 903 antibody, are essential for distinguishing PMC from cribriform
      clear cell hyperplasia (CCCH), typical tubular hyperplasia and tubular
      transitional metaplasia, tubular, microtubular and cribriform basal cell
      hyperplasias, post-undeveloped prepuberal (PUPPUH), florid (FH) and mesonephric
      remnant hyperplasias. Moreover, the hyperplastic basal cells are also
      immunostained for prostatic specific antigen (PSA). The identification of
      myoepithelial cells (positive for keratin 903, actin and S100 protein antibodies)
      allow the diagnosis of prostatic sclerosing adenosis. Basement membrane (BM) and
      BCL are focally absent in post-atrophic hyperplasia (PAH), PUPPUH, FH and in
      extratubulo-alveolar gemmations of dysplasic lesions such as prostatic
      intraepithelial neoplasia (PIN), adenomatous atypical hyperplasia (AAH) and
      adenosis, where hypercromatic nuclei and enlarged nucleoli are the most important
      cytological criteria for defining malignant changes. Two putative oncogenic
      stages have been identified in the present work on these morphological grounds by
      critically examining the histogenetic hypoteses given in the literature on PMC
      precursors. The first is characterized by precancerous conditions such as PAH,
      PUPPUH, CCCH and FH that may become dysplastic though not necessarily; the second
      includes precancerous lesions, namely atypical tubulo-alveolar budding-in or
      budding-off as PIN and AAH, respectively, that may evolve towards PMC. The
      histogenesis of rare prostatic carcinomas are also considered. Basal cell and
      adenoid-cyst carcinomas seem to originate from atypical basal cell proliferations
      and metaplastic (transitional, adenosquamous, mucinous) carcinomas from basal and
      columnar-cells. Transitional and endometrioid carcinomas affect the mesonephric
      part of the prostate. Prostatic endocrine cells may give rise to carcinoid
      tumors, whereas some well-differentiated or anaplastic carcinomas may present
      more or less numerous endocrine cells and/or Paneth-like cells by means of a
      prosoplastic and ketaplastic process from neoplastic elements that underwent a
      stem cell backward differentiation.

PMID- 7524012
TI  - [Preoperative cytodiagnosis by needle aspiration of follicular thyroid lesions].
AB  - In the period 1989-92, 2729 F.N.A.B. were performed: 585 with an histological
      control were reviewed. The aim of the study was to evaluate the risk of
      carcinomatous occurrence in the follicular-structured smears and to suggest a new
      cytodiagnostic classification. Out of 398 follicular-structured smears, 188 were
      colloid nodules (CN), 38 thyreocytic hyperplasias without nuclear atypia (THWNA),
      146 predominantly follicular lesions (PFL), 26 follicular lesions with nuclear
      pleomorphism (FLWNP). The last one showed a high incidence of neoplasia (69.2%)
      and carcinoma (46.1%); the second and the third only a difference in the
      incidence of benign neoplasms (32.9 vs. 15.8%), with almost the same percentage
      of occurrence of malignancies (2.6 vs. 2.1%). Such results suggest that a six
      months dilatory strategy might be useful in simple follicular lesions (THWNA and
      PFL) whereas a cytological follicular pattern with nuclear pleomorphism requires
      a surgical treatment for the high risk of carcinomatous occurrence.

PMID- 7524013
TI  - Insulin-like growth factor binding protein-3 concentrations and insulin-like
      growth factor binding protein-3 protease activity in sera of patients with
      malignant solid tumors or leukemia.
AB  - IGF binding proteins (IGFBP) regulate the bioavailability and bioactivity of IGF.
      The major IGFBP in serum is IGFBP-3. We investigated whether sera from children
      with malignancies show alterations in levels of IGFBP-3 as measured by Western
      ligand blot analysis (WLB) and RIA with alpha IGFBP-3gl, a specific rabbit
      polyclonal antibody. Furthermore, IGFBP-3 proteolysis was quantified by
      densitometric analysis of [125I]IGFBP-3 protease assays, and IGFBP-3 fragments
      were visualized by Western immunoblot with alpha IGFBP-3gl. We examined sera from
      21 children with solid tumors, five patients with sarcoma who had reached
      complete remission, and 13 children with acute leukemia. Serum samples were
      collected at diagnosis, before initiation of therapy. Sera of 10 healthy children
      served as normal controls. Children with solid tumor or leukemia had
      significantly higher (p < 0.001) IGFBP-3 protease activity in serum than did
      normal controls or patients with sarcoma in complete remission. Corresponding to
      this finding, densitometry of WLB showed lower IGFBP-3 levels in sera of children
      with malignancies in comparison with normal controls. The negative correlation (p
      < 0.001, r = -0.80) between IGFBP-3 proteolysis, as measured by [125I]IGFBP-3
      protease assay, and IGFBP-3 band density on WLB indicates that proteolysis is the
      probable reason for reduction of IGFBP-3 on WLB. IGFBP-3 concentrations measured
      by RIA were in the normal range for most patients, further indicating that
      differences in serum IGFBP-3 levels measured by WLB reflect protease
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524015
TI  - Psychosocial, behavioral, and medical outcomes in children with epilepsy: a
      developmental risk factor model using longitudinal data.
AB  - OBJECTIVE: We studied factors predicting the risk of adverse long-term
      psychosocial, behavioral, and medical outcomes in children with epilepsy.
      METHODS: Children (N = 157, 4.5 to 13 years) were enrolled in a prospective
      longitudinal study when first seen. Potential subjects were excluded if they were
      moderately or severely mentally retarded, had motor or sensory handicaps
      interfering with testing, or did not speak either English or Spanish. MEASURES:
      To develop risk predictors, we collected information regarding the child's
      medical and seizure history, cognitive functioning, and behavior problems, and
      family functioning. Children and their families were followed for a minimum of 18
      months, then underwent reassessment of medical status, parent's attitudes toward
      epilepsy, and the child's behavioral and cognitive functioning. Data were
      analyzed by confirmatory factor analysis to develop baseline factors
      (Sociocultural Risk, Seizure Risk, and Behavior Problems) and outcome factors
      (Medical/Seizure Problems, Parent's Negative Attitudes Toward Epilepsy, and
      Behavior Problems), followed by structural equation modeling to determine across
      time causal effects. Eighty-eight subjects completed all baseline and outcome
      measures. RESULTS: Among significant across-time effects, Medical Outcome was
      predicted by Seizure Risk. An increased number of stressful life events predicted
      better Medical Outcome. Low acculturation increased Parent's Negative Attitudes
      and was associated with increased Behavior Problems at baseline. Behavior
      Problems were stable across time. It is interesting that IQ did not affect any of
      the outcomes, although its effect may have been mediated through other baseline
      measures. CONCLUSIONS: Seizure history was the best predictor of ongoing medical
      difficulties, whereas the most important causes of ongoing parental anxiety and
      negative attitudes toward epilepsy were sociocultural. Variation in medical or
      attitudinal outcomes was not influenced by either the child's IQ or reported
      behavioral problems. These findings suggest that to alter attitudes toward
      epilepsy, programs should be tailored to the sociocultural background of the
      family. Studies of quality of life of children with epilepsy should include
      appropriate sociocultural measures.

PMID- 7524014
TI  - Myogenic response in large pulmonary arteries and its ontogenesis.
AB  - To evaluate the myogenic response and its ontogeny in large pulmonary arteries,
      we studied 45 newborn and 30 adult guinea pigs. Compared with the those of the
      adult, the newborn arterial vessels possessed a significantly (p < 0.01) smaller
      diameter (1153 +/- 34 versus 1656 +/- 65 microns), static compliance (2.2 +/- 0.3
      versus 4.6 +/- 0.7 microns/mN), and active stress (3.4 +/- 0.4 versus 5.8 +/- 0.7
      mN/mm2). Stretch-induced contraction was obtained by quick stretch of the vessel
      segments to 120, 140, 160, 180, or 200% of their optimal length, and the myogenic
      response was measured as the change in force after muscle relaxation with
      papaverine. A myogenic response was observed in 94% of the newborn and 93% of
      adult vessel segments, and significant age differences in the response were
      present. The magnitude of the active force generated for any stretch over 120%
      was significantly greater in the newborn (p < 0.01), and as a percentage of K+
      (127 mM) stimulation, a 2-fold stretch of the vessels' optimal length resulted in
      a force of 1073 +/- 159% in the newborn compared with 51 +/- 16% in the adult (p
      < 0.01). The myogenic response in these large pulmonary vessels was completely
      suppressed by a calcium channel blocker (D-600) but unaltered by addition of a
      nitric oxide synthase inhibitor (NG-methyl-L-arginine) or indomethacin. We
      conclude that the large pulmonary arterial vessels of the guinea pig exhibit a
      powerful stretch-induced myogenic response that is greater in the newborn
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524016
TI  - Effects of learning modalities on melodic and rhythmic retention and on vocal
      pitch-matching by preschool children.
AB  - To assess whether melodic and rhythmic retention as well as pitch-matching
      ability could be improved through use of learning modalities, 61 children ages 4
      and 5 years were presented music instruction in one of four ways, visually
      (seeing visual aids with the music), auditorily (singing and listening),
      kinesthetically (moving to music), or through multimodal presentations. Analysis
      indicated that preschool children receiving the auditory and multimodal
      treatments scored significantly higher on both the melodic and rhythmic posttests
      than on pretests. Children receiving kinesthetic treatment scored significantly
      lower on both the melodic and rhythmic posttests than the other three classes.
      Further, children in the auditory and multimodal classes matched pitch
      significantly better at posttest than children in either the visual or
      kinesthetic classes.

PMID- 7524017
TI  - [Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG
      CSF) on recovery from neutropenia induced by fractionated irradiation in mice].
AB  - The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF)
      on the recovery from neutropenia induced by fractionated whole-body irradiation
      was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten
      exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral
      neutropenia with a nadir on day 17 was caused by the fractionated irradiation.
      Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 micrograms/body/day from
      day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The
      kinetics of morphologically identifiable bone marrow cells were studied to
      clarify the mechanism behind the promotive effect of this factor. A slight
      decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and
      myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow
      neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice.
      Treatment using rhG-CSF caused an increase in immature granulocytes of all
      differential stages in the femur. Microscopic findings of the femurs and spleens
      also revealed an increase in immature granulocytes in these organs in mice
      injected with rhG-CSF. These results indicate that rhG-CSF accelerates
      granulopoiesis in the femur and spleen, thereby promoting recovery from
      neutropenia induced by fractionated irradiation.

PMID- 7524018
TI  - [Biochemical markers in RA].
AB  - Inflammatory activity is usually (but not always) accompanied by increases in the
      plasma concentrations of acute-phase reactants such as C-reactive protein (CRP),
      fibrinogen etc. The most widely used and most sensitive variable is the CRP
      value. Increase in the concentrations of acute-phase reactants is accompanied by
      increase in the ESR (erythrocyte sedimentation rate), though increase in ESR may
      also be secondary to hypergammaglobulinaemia and anaemia without co-existing
      inflammation. The measurement of various connective tissue markers in the blood,
      synovial fluid and urine has opened up the way to new possibilities for
      evaluating synovial inflammation, pannus formation, and cartilage and bone
      destruction.

PMID- 7524019
TI  - Compilation of small RNA sequences.
AB  - This is an update containing small RNA sequences deposited in GenBank recently.
      Over four hundred small RNA sequences are available in this and earlier
      complications.

PMID- 7524020
TI  - The signal recognition particle database (SRPDB).
AB  - The SRPDB (signal recognition particle database) provides aligned SRP RNA and
      protein sequences, annotated and phylogenetically ordered. This release includes
      82 SRP RNAs (including 22 bacterial and 9 archaeal homologs) and a total of 20
      protein sequences representing SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72. The
      offerings also include representative RNA secondary structure diagrams.

PMID- 7524021
TI  - The Ribosomal Database Project.
AB  - The Ribosomal Database Project (RDP) is a curated database that offers ribosome
      related data, analysis services, and associated computer programs. The offerings
      include phylogenetically ordered alignments of ribosomal RNA (rRNA) sequences,
      derived phylogenetic trees, rRNA secondary structure diagrams, and various
      software for handling, analyzing and displaying alignments and trees. The data
      are available via anonymous ftp (rdp.life.uiuc.edu), electronic mail
      (server/rdp.life.uiuc.edu) and gopher (rdpgopher.life.uiuc.edu). The electronic
      mail server also provides ribosomal probe checking, approximate phylogenetic
      placement of user-submitted sequences, screening for chimeric nature of newly
      sequenced rRNAs, and automated alignment.

PMID- 7524022
TI  - Database on the structure of small ribosomal subunit RNA.
AB  - The database on small ribosomal subunit RNA structure contains (June 1994) 2824
      nucleotide sequences. All these sequences are stored in the form of an alignment
      based on the adopted secondary structure model, which in turn is corroborated by
      the observation of compensating substitutions in the alignment. The complete
      database is made available to the scientific community through anonymous ftp on
      our server in Antwerp. A special effort was made to improve electronic retrieval
      and a program is supplied that allows to create different file formats. The
      database can also be obtained from the EMBL nucleotide sequence library.

PMID- 7524023
TI  - Database on the structure of large ribosomal subunit RNA.
AB  - A database on large ribosomal subunit RNA is made available. It contains 258
      sequences. It provides sequence, alignment and secondary structure information in
      computer-readable formats. Files can be obtained using ftp.

PMID- 7524024
TI  - Collection of small subunit (16S- and 16S-like) ribosomal RNA structures: 1994.
AB  - A collection of diverse 16S and 16S-like rRNA secondary structure diagrams are
      available. This set of rRNAs contains representative structures from all of the
      major phylogenetic groupings--Archaea, (eu)Bacteria, and the nucleus,
      mitochondrion, and chloroplast of Eucarya. Within this broad phylogenetic
      sampling are examples of the major forms of structural diversity currently known
      for this class of rRNAs. These structure diagrams are available online through
      our computer-network WWW server and anonymous ftp, as well as from the author in
      hardcopy format.

PMID- 7524025
TI  - The Ribonuclease P database.
AB  - The Ribonuclease P Sequence database is a compilation of RNase P sequences,
      sequence alignments, secondary structures, three-dimensional models, and
      accessory information. In its initial form, the database contains information on
      RNase P RNA in bacteria and archaea, and RNase P protein in bacteria. The
      sequences themselves are presented phylogenetically ordered and aligned. The
      database also contains secondary structures of bacterial and archaeal RNAs,
      including specially annotated 'reference' secondary structures of Escherichia
      coli and Bacillus subtilis RNase P RNAs, a minimum phylogenetic consensus
      structure, and coordinates for models of three-dimensional structure.

PMID- 7524026
TI  - The single pseudouridine residue in Escherichia coli 16S RNA is located at
      position 516.
AB  - The number and location of pseudouridine residues in Escherichia coli 16S
      ribosomal RNA has been determined by a combination of direct and indirect
      methods. Only one residue was found, at position 516. This site is at the 5'-end
      of one of the three most highly conserved long sequences of this RNA molecule. A
      number of experimental findings have strongly implicated this loop in the
      fidelity of codon recognition by A-site bound tRNA. By virtue of its location, we
      suggest that psi 516 may also play a role in maintaining the fidelity of protein
      synthesis.

PMID- 7524027
TI  - Nuclear-encoded mitochondrial tRNAs of Trypanosoma brucei have a modified
      cytidine in the anticodon loop.
AB  - The mitochondrial genome of Trypanosoma brucei does not appear to encode any tRNA
      genes. Isolated organellar tRNAs hybridize to nuclear DNA, suggesting that they
      are synthesized in the nucleus and subsequently imported into the mitochondrion.
      Most imported tRNAs have cytosolic counterparts, showing identical mobility on
      two-dimensional polyacrylamide gels. We have compared three nuclear-encoded
      mitochondrial tRNAs (tRNA(Lys), tRNA(Leu), tRNA(Tyr)) with their cytosolic
      isoforms by direct enzymatic sequence analysis. Our findings indicate that the
      primary sequences of the mitochondrial and the corresponding cytosolic tRNAs are
      identical. However, we have identified a mitochondrion-specific nucleotide
      modification of each tRNA which is localized to a conserved cytidine residue at
      the penultimate position 5' of the anticodon. The modification present in mature
      mitochondrial tRNA(Tyr) was not found in a mutant tRNA(Tyr) defective in splicing
      in either cytosolic or mitochondrial fractions. The mutant tRNA(Tyr) has been
      expressed in transformed cells and its import into mitochondria has been
      demonstrated, suggesting that the modified cytidine residue is not required for
      import and therefore may be involved in adapting imported tRNAs to specific
      requirements of the mitochondrial translation machinery.

PMID- 7524028
TI  - Quantitative analysis of RNA cleavage during RNA-directed DNA synthesis by human
      immunodeficiency and avian myeloblastosis virus reverse transcriptases.
AB  - We have determined the extent of RNA cleavage carried out during DNA synthesis by
      either human immunodeficiency virus (HIV) or avian myeloblastosis virus (AMV)
      reverse transcriptases (RTs). Conditions were chosen that allowed the analysis of
      the cleavage and synthesis performed by the RT during one binding event on a
      given template-primer. The maximum quantity of ribonuclease H (RNase H) sensitive
      template RNA left after synthesis by the RTs was determined by treatment with
      Escherichia coli RNase H. RNA cleavage products that were expected to be too
      short to remain hybridized, less than 13 nucleotides in length, were quantitated.
      Results showed that HIV- and AMV-RT degraded about 80% and less than 20%,
      respectively, of the potentially degradable RNA to these short products. Survival
      of longer, hybridized RNA was not a result of synthesis by a population of RTs
      that had selectively lost RNase H activity. Using an assay that evaluated the
      proportion of primers extended versus RNA templates cleaved during primer
      extension by the RTs, we determined that essentially each molecule of HIV- and
      AMV-RT with polymerase also has RNase H activity. The results indicate that
      although both HIV- and AMV-RTs cleave the RNA template during synthesis, the
      number of cleavages per nucleotide addition with HIV-RT is much greater. They
      also suggest that some hybridized RNA segments remain right after the passage of
      the RT making the first DNA strand. In vivo, these segments would have to be
      cleaved or displaced in later reactions before second strand DNA synthesis could
      be completed.

PMID- 7524031
TI  - A rapid and simple PCR-based method for isolation of cDNAs from differentially
      expressed genes.
AB  - Recently two techniques have been reported which use arbitrarily primed RT-PCR
      amplification of cDNA fragments from subsets of mRNAs to detect cDNA fragments
      from differentially expressed mRNAs. Here we report a simple and rapid PCR-based
      protocol to both detect and isolate cDNA fragments of up to 3000 base pairs from
      differentially expressed genes in two easy steps. To generate cDNAs from most
      mRNAs, the first step consisted of reverse transcription using a fully
      degenerated 6-mer oligonucleotide as primer. The second step consisted of PCR
      amplification of internal regions of the cDNAs with two or three longer primers
      with arbitrary but defined sequences. DNA fragments were easily displayed by
      agarose gel electrophoresis and then excised for direct use in cloning,
      sequencing, and Northern blot analysis. By repeating the PCR amplification
      (second step) on the same cDNA templates (first step) ten times with different
      sets of primers, over 170 discrete cDNA fragments were obtained from a single
      tissue. By combining the two-step procedure with 3'-RNA-anchored cDNA extension,
      additional DNA fragments can be generated from the same mRNA. The new procedure
      was used here to define 3600 bp of a new brain-specific mRNA.

PMID- 7524030
TI  - Extension of helix II of an HIV-1-directed hammerhead ribozyme with long
      antisense flanks does not alter kinetic parameters in vitro but causes loss of
      the inhibitory potential in living cells.
AB  - When designed to cleave a target RNA in trans, the hammerhead ribozyme contains
      two antisense flanks which form helix I and helix III by pairing with the
      complementary target RNA. The sequences forming helix II are contained on the
      ribozyme strand and represent a major structural component of the hammerhead
      structure. In the case of an inhibitory 429 nucleotides long trans-ribozyme (2as
      Rz12) which was directed against the 5'-leader/gag region of the human
      immunodeficiency virus type 1 (HIV-1), helix II was not pre-formed in the single
      stranded molecule. Thus, major structural changes are necessary before cleavage
      can occur. To study whether pre-formation of helix II in the non-paired 2as-Rz12
      RNA could influence the observed cleavage rate in vitro and its inhibitory
      activity on HIV-1 replication, we extended the 4 base pair helix II of 2as-Rz12
      to 6, 10, 21, and 22 base pairs respectively. Limited RNase cleavage reactions
      performed in vitro at 37 degrees C and at physiological ion strength indicated
      that a helix II of the hammerhead domain was pre-formed when its length was at
      least six base pairs. This modification neither affected the association rate
      with target RNA nor the cleavage rate in vitro. In contrast to this, extension of
      helix II led to a significantly decreased inhibition of HIV-1 replication in
      human cells. Together with the finding of others that shortening of helix II to
      less than two base pairs reduces the catalytic activity in vitro, this
      observation indicates that the length of helix II in the naturally occurring RNAs
      with a hammerhead domain is already close or identical to the optimal length for
      catalytic activity in vitro and in vivo.

PMID- 7524029
TI  - Matrix assisted laser desorption/ionization mass spectrometry of enzymatically
      synthesized RNA up to 150 kDa.
AB  - Enzymatically synthesized RNA samples (in vitro transcripts) were analysed by
      matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). Spectra
      of RNA up to 150 kDA (461 nucleotides) are shown. Polymerase generated sample
      heterogeneity and its contribution to mass resolution are discussed. A time
      course exonuclease digest of a 55 nt in vitro transcript was analyzed to
      investigate the performance of MALDI-MS on complex mixtures. Based on these data,
      the analysis by MALDI-MS of DNA sequencing reactions, produced by the action of
      an RNA polymerase, is discussed.

PMID- 7524032
TI  - Solid phase assays for the detection of inhibitors of HIV reverse transcriptase.

PMID- 7524033
TI  - Trypanosoma brucei mitochondria contain RNA helicase activity.
AB  - Mitochondrial gene expression in kinetoplastid organisms such as Trypanosoma,
      Leishmania and Crithidia requires a posttranscriptional RNA processing event
      known as kRNA editing. During editing, uridine nucleotides get inserted and
      deleted into pre-mRNAs directed by small, metabolically stable RNAs, termed guide
      RNAs. Although the precise mechanism of the reaction is not understood, the
      accepted working model describes the formation of extended anti-parallel RNA
      helices between gRNA molecules with pre- and partially edited mRNAs as
      intermediates. These duplex structures must be separated to ensure the sequential
      action of multiple gRNAs in a 3' to 5' polarity on the mRNA molecule. In spite of
      this fact, no unwinding activity has heretofore been identified in kinetoplastid
      mitochondria. We report the characterisation of a RNA helicase activity within
      Trypanosoma brucei mitochondrial extracts. The activity unwinds 25- and 48 bp,
      tailed RNA duplex structures but fails to separate DNA strands. It can be
      destroyed by heat denaturation as well as by proteinase K treatment. The activity
      requires magnesium cations and acts in a NTP/dNTP dependent manner. Hydrolysis of
      a nucleoside triphosphate is required rather than mere NTP binding as deduced
      from a comparison of unwinding in the presence of ATP and AMP-PCP. RNA duplexes
      mimicking presumed kRNA editing intermediates are substrates of the unwinding
      activity and therefore, we address the possible involvement of a RNA helicase
      activity during kRNA editing.

PMID- 7524034
TI  - Characterization of RNA binding specificity of the Drosophila sex-lethal protein
      by in vitro ligand selection.
AB  - The Drosophila sex-lethal (Sxl) protein, a regulator of somatic sexual
      differentiation, is an RNA binding protein with two potential RNA recognition
      motifs (RRMs). It is thought to exert its function on splicing by binding to
      specific RNA sequences within Sxl and transformer (tra) pre-mRNAs. To examine the
      Sxl RNA binding specificity in detail, we performed in vitro selection and
      amplification of ligand RNAs from a random sequence pool on the basis of affinity
      with Sxl protein. After three cycles of selection and amplification, we cloned
      and sequenced 17 cDNAs corresponding to the RNAs selected in vitro. Sequencing
      showed that most of the RNAs selected contain polyuridine stretches surrounded by
      purine residues. In vitro binding analysis revealed that the sequences of the in
      vitro selected RNAs with relatively high affinity for Sxl show similarity to that
      of the Sxl- and tra-regulated acceptor regions, including the invariant AG
      sequence for splicing. These results suggest that Sxl recognizes and
      preferentially binds to a polyuridine stretch with a downstream AG sequence.

PMID- 7524036
TI  - Identity of the RNA-binding protein K of hnRNP particles with protein H16, a
      sequence-specific single strand DNA-binding protein.
AB  - Protein H16, which we have identified previously in mammalian cell lines, binds
      in vitro to two single stranded DNA sites on the late strand of the early
      promoter of SV40. It has no other single strand binding site in the SV40 genome
      and does not bind to double stranded DNA. In vitro, H16 can be shown to stimulate
      strongly the activity of purified RNA polymerase II. Here we have purified this
      70 kDa protein from cultured monkey cells and have sequenced three of its tryptic
      peptides. The analysis indicates that H16 is the simian homolog of human protein
      K, a nuclear RNA-binding protein found in heterogeneous nuclear ribonucleoprotein
      (hnRNP) particles, which contains a KH domain present in several proteins
      including the fragile X mental retardation gene product (FMR1). The binding
      affinities of protein K/H16 for RNA and DNA were subsequently compared in detail.
      They showed that under conditions where K/H16 binds strongly to its single
      stranded DNA site, it binds very weakly to the corresponding RNA sequence. This
      result suggests a possible shuttling of the protein from RNA to DNA during
      processes which involve opening of the DNA double helix.

PMID- 7524035
TI  - Interaction of the 3'-end of tRNA with ribonuclease P RNA.
AB  - Ribonuclease P, which contains a catalytic RNA subunit, cleaves 5' precursor
      specific sequences from pre-tRNAs. It was previously shown that the RNase P RNA
      optimally cleaves substrates which contain the mature, 3'-terminal CCA of tRNA.
      In order to determine the contributions of those individual 3'-terminal
      nucleotides to the interaction, pre-tRNAs that have CCA, only CC or C or are
      without CCA at the 3'-end were synthesized by run-off transcription, tested as
      substrates for cleavage by RNase P RNA and used in photoaffinity crosslinking
      experiments to examine contact sites in the ribozyme. In order to generalize the
      results, analyses were carried out using three different bacterial RNase P RNAs,
      from Escherichia coli, Bacillus subtilis and Thermotoga maritima. At optimal
      (Kcat/Km) ionic strength (1 M NH4+/25 mM Mg2+), Km increases incrementally 3- to
      10-fold upon stepwise removal of each nucleotide from the 3'-end. At high ionic
      strength (2 M NH4+/50 mM Mg2+), which suppresses conformational effects, removal
      of the 3'-terminal A had little effect on Km, indicating that it is not a
      specific contact. Analysis of the deletion and substitution mutants indicated
      that the C residues act specially; their contribution to binding energy at high
      ionic strength (approximately 1 kcal/mol) is consistent with a non-Watson-Crick
      interaction, possibly irregular triple-strand formation with some component of
      the RNase P RNA. In agreement with previous studies, we find that the RNase P
      holoenzyme in vitro does not discriminate between tRNAs containing or lacking
      CCA. The structural elements of the three RNase P RNAs in proximity to the 3'-end
      of tRNA were examined by photoaffinity crosslinking. Photoagent-labeled tRNAs
      with 3'-terminal CCA, only CC or C, or lacking all these nucleotides were
      covalently conjugated to the three RNase P RNAs by irradiation and the sites of
      crosslinks were mapped by primer extension. The main crosslink sites are located
      in a highly conserved loop (probably an irregular helix) that is part of the core
      of the RNase P RNA secondary structure. The crosslinking results orient the CCA
      of tRNA with respect to that region of the RNase P RNA.

PMID- 7524038
TI  - Antisense oligonucleotides in solution or encapsulated in immunoliposomes inhibit
      replication of HIV-1 by several different mechanisms.
AB  - Phosphodiester and phosphorothioate oligonucleotides in alpha and beta
      configurations directed against the initiation codon region of the HIV-1 rev gene
      were evaluated for their ability to inhibit HIV-1 replication in acutely and
      chronically infected human CEM cells. Encapsulation in antibody-targeted
      liposomes (immunoliposomes) permitted intracellular delivery and distinction
      between oligonucleotide-mediated inhibition of viral entry and intracellular
      effects on viral RNA. Our results are consistent with four mechanisms of
      antiviral activity for these antisense oligonucleotides: (i) interference with
      virus-mediated cell fusion by free but not liposome-encapsulated phosphorothioate
      oligonucleotides of any sequence; (ii) interference with reverse transcription in
      a sequence non-specific manner by phosphorothioate oligonucleotides in alpha and
      beta configurations; (iii) interference with viral reverse transcription in a
      sequence-specific and RNase-H-independent manner by alpha and beta phosphodiester
      oligonucleotides; (iv) interference with viral mRNA in a sequence-specific and
      RNase-H-dependent manner by beta-phosphorothioate oligonucleotides.

PMID- 7524039
TI  - RT-PCR: 'background priming' during reverse transcription.

PMID- 7524041
TI  - The role of parasympathetic modulation of the reentrant arrhythmic substrate in
      the genesis of sustained ventricular tachycardia.
AB  - The influence of parasympathetic activity on the reentrant arrhythmic substrate
      in the genesis of sustained ventricular tachycardia remains unclear. To assess
      this influence, we studied the heart rate variability in 59 patients referred for
      invasive electrophysiological testing. In addition, the presence of late
      potentials and high grade ventricular ectopy, and the left ventricular ejection
      fraction was determined. The 28 patients with inducible sustained ventricular
      tachycardia were found to have lower heart rate variability by time- and
      frequency-domain measurements over 24 hours when compared to the 31 subjects who
      were noninducible. PNN50 was 4% in the inducible patients, whereas it was 9% in
      the subjects who were noninducible (P = 0.03). Similarly, HFP24H was 9 and 14
      msec, respectively (P = 0.02). MAXHFP1H also differed (20 vs 27 msec [P = 0.04])
      but not MINHFP1H (5 vs 6 msec). There was no association between heart rate
      variability and late potentials, degree of ventricular ectopy, or left
      ventricular ejection fraction. Thus, vagal tone does not appear to correlate with
      the presence of late potentials, ventricular ectopy, or left ventricular
      dysfunction. Low mean as well as maximal vagal tone, in contrast to minimal vagal
      tone, predicts inducibility of sustained ventricular tachycardia. Our data
      suggest that the inability to modulate parasympathetic tone appears to be an
      important determinant in the genesis of reentrant sustained ventricular
      tachycardia.

PMID- 7524040
TI  - A reexamination of the association between HOME scores and income.
AB  - This study, which represents another look at the relationship between the HOME
      Inventory and income, uses data from the Infant Health and Development Program
      (IHDP), a multisite, longitudinal study of low-birth-weight preterm infants. Two
      versions of the HOME Inventory were used: The Infant/Toddler (IT-HOME), at 12
      months of age, and the Early Childhood (EC-HOME), at 36 months of age. Predictor
      variables were income, ethnicity, maternal education, parity, gestational age,
      marital status, maternal age, and site. HOME scores were positively correlated
      with income. However, after controlling for the other variables in the models,
      the portion of the variance in HOME scores uniquely explained by income was quite
      low (IT-HOME, 5.1%; EC-HOME, 4.2%). Finally, the relationship between HOME scores
      and four child characteristics (cognitive development, growth, maladaptive
      behavior, and social competence) measured when the child was 36 months old were
      investigated using correlation. The results indicated that the quality of the
      home environment, as measured by the HOME Inventory, is related to children's
      development.

PMID- 7524037
TI  - An approach to the structure determination of nucleic acid analogues hybridized
      to RNA. NMR studies of a duplex between 2'-OMe RNA and an oligonucleotide
      containing a single amide backbone modification.
AB  - The backbone modification amide-3, in which -CH2-NH-CO-CH2- replaces -C5'H2-O5'
      PO2-O3'-, is studied in the duplex d(G1-C2-G3-T4.T5-G6-C7-G8)*mr(C9-G10-C11-A12
      A13-C14-G15+ ++-C16) where . indicates the backbone modification and mr indicates
      the 2'-OMe RNA strand. The majority of the exchangeable and non-exchangeable
      resonances have been assigned. The assignment procedure differs from standard
      methods. The methyl substituent of the 2'-OMe position of the RNA strand can be
      used as a tool in the interpretation. The duplex structure is a right-handed
      double helix. The sugar conformations of the 2'-OMe RNA strand are predominantly
      N-type and the 2'-OMe is positioned at the surface of the minor groove. In the
      complementary strand, only the sugar of residue T4 is found exclusively in N-type
      conformation. The incorporation of the amide modification does not effect very
      strongly the duplex structure. All bases are involved in Watson-Crick base pairs.

PMID- 7524042
TI  - Diagnosis of ventricular tachycardia using a pacemaker Holter function.
AB  - The diagnosis of ventricular tachycardia (VT) using the Holter function of an
      implanted pacemaker has not yet been reported. We present the case of a patient
      with episodes of slow VT, hemodynamically stable, but in whom long lasting
      attacks were not identified by the patient as VT recurrences, finally leading to
      progressive heart failure. Prospective analysis of the 24-hour ECG and comparison
      with the pacemaker Holter data allowed us to determine diagnostic criteria to
      recognize VT using the pacemaker Holter function. Using these criteria it was
      possible to retrospectively diagnose VT occurrence during the weeks when the
      patient was out-of-hospital.

PMID- 7524043
TI  - Risperidone.
AB  - Risperidone, a benzisoxazole derivative, is a novel antipsychotic agent that has
      an extremely strong binding affinity for serotonin 5-HT2 receptors, a strong
      binding affinity for dopamine D2 receptors, and a high affinity for alpha 1- and
      alpha 2-adrenergic receptors and histamine H1 receptors. Its affinity for
      serotonin receptors is approximately 200 times greater than that of haloperidol,
      and its dopamine antagonistic potency is comparable to that of haloperidol. Its
      major metabolite, 9-hydroxyrisperidone, has similar pharmacologic activity, and
      thus the parent compound and metabolite form the active antipsychotic moiety.
      Clinical trials demonstrate that risperidone is an effective antipsychotic agent
      that improves negative as well as positive symptoms of schizophrenia. At
      recommended dosages, the frequency of extrapyramidal side effects is no greater
      than that seen with placebo. The drug appears to be an advance in the treatment
      of psychoses.

PMID- 7524044
TI  - Use of in vitro and in vivo data in the design, development, and quality control
      of sustained-release decongestant dosage forms.
AB  - STUDY OBJECTIVES: To investigate the use of in vitro and in vivo data in the
      development of a sustained-release, carbomer-based dosage form (Entex LA
      tablets); and to compare the in vitro dissolution of pseudoephedrine from a
      sustained-release, hydroxypropylcellulose-based dosage form (Entex PSE tablets)
      and four branded competitors with different sustained-release matrixes. DESIGN:
      Entex LA: In vitro testing by rotating bottle method and in vivo testing as
      double-blind, randomized, crossover, 24-hour study. Entex PSE and four
      competitors: in vitro testing by paddle method. SETTING: A pharmaceutical
      research and development facility. PATIENTS: Fifteen health, adult, volunteer
      Caucasian men between ages 18 and 40 years. MAIN RESULTS: Three formulations of
      Entex LA, varying in carbomer content by 3-5%, were studied. As carbomer content
      increased, in vitro dissolution rate directionally decreased. Plasma
      concentrations of active ingredients guaifenesin and phenylpropanolamine were
      also slightly although directionally decreased. The in vitro method was sensitive
      to small changes in carbomer content. Larger changes in carbomer content would be
      required to establish an in vitro-in vivo correlation. The in vitro comparison of
      Entex PSE and four similar branded products showed important differences in
      dissolution profiles. The mean cumulative release of pseudoephedrine from Entex
      PSE was 39% at 1.5 hours, 62% at 4.0 hours, and 80% at 8.0 hours. The other
      products released pseudoephedrine more rapidly, with the two fastest-dissolving
      products releasing 61-62% in the first 1.5 hours. CONCLUSIONS: Sustained-release,
      polymer-based dosage forms such as Entex LA and Entex PSE can be complex and pose
      special challenges in design, development, and reformulation. For Entex LA,
      changes in polymer concentration and dye system influenced the in vitro
      (dissolution) performance. In vivo (plasma) data helped establish a defined range
      in which carbomer concentration could be varied to achieve the best manufacturing
      performance without affecting product performance. For Entex PSE and four branded
      competitor products, the cumulative in vitro release (dissolution) of
      pseudoephedrine varied widely. Release from Entex PSE was more consistent and
      more gradual than that from some of the comparison products. Because the
      absorption rate of the active ingredients pseudoephedrine and gauifenesin is
      governed by the dissolution rate, the observed differences suggest that the
      products tested may differ in biologic performance. Although in vitro dissolution
      data may not necessarily correlate with in vivo differences in clinical safety or
      efficacy, the potential for unexpected product performance may be signaled by
      inconsistent in vitro dissolution characteristics, especially for sustained
      release dosage forms.

PMID- 7524048
TI  - Metabolism of substance P and neurokinin A by human vascular endothelium and
      smooth muscle.
AB  - Analysis of SP and NKA metabolism by human vascular endothelium, relative to that
      in human plasma, identified integrative, multiple pathways for the processing of
      circulating SP (but not NKA) by angiotensin-converting enzyme (ACE; EC 3.4.15.1),
      dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5), and aminopeptidase M (AmM;
      EC 3.4.11.2). In contrast, SP and NKA, which may diffuse into or be neurally
      released within the vessel wall, were both metabolized by smooth muscle neutral
      endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11). Collectively, these studies
      indicate peptide-specific and site-specific differential processing of SP and NKA
      by human plasma and vasculature.

PMID- 7524047
TI  - Attenuation of hippocampal kainic acid-induced seizures by substance P treatment.
AB  - Adult male Wistar rats (n = 21) received bilateral kainic acid lesions of their
      hippocampi. Over a period of 9 weeks the animals received daily IP injections of
      either 5 micrograms/kg or 50 micrograms/kg substance P (SP) or vehicle. Seizures
      provoked by the lesions were suppressed by the daily administration of the
      neuropeptide SP in a dose of 50 micrograms/kg for the whole period of
      observation. The neurokinin significantly (p < 0.01) reduced the number of
      seizures compared to the vehicle-treated animals.

PMID- 7524049
TI  - Purification and primary structure of galanin from the alligator stomach.
AB  - Galanin-like immunoreactivity (6 pmol/g tissue) was detected by radioimmunoassay
      in an extract of the stomach of the alligator, Alligator mississipiensis, but the
      peptide was present only in low concentration (< 0.5 pmol/g) in extracts of the
      brain and small intestine. Alligator galanin comprises 29 amino acid residues and
      contains an alpha-amidated C-terminal residue. Residues 1-22 of alligator galanin
      are identical to the corresponding sequence in pig/sheep/rat galanins,
      demonstrating that strong evolutionary pressure has acted to conserve the
      receptor-binding domain of the peptide. Unexpectedly, in view of the close
      phylogenetic relationship between crocodilians and birds, alligator galanin is
      structurally more similar to sheep galanin (three amino acid substitutions) than
      to chicken galanin (four amino acid substitutions).

PMID- 7524046
TI  - Neuropeptide Y and galanin are coexpressed in rat large type A sensory neurons
      after peripheral transection.
AB  - Neuropeptide Y (NPY)-like immunoreactivity (IR) was observed in 20-30% of
      ipsilateral dorsal root ganglion (DRG) neurons (L4-5) after unilateral
      transection of rat sciatic nerve. Most of these neurons contained 200 kDa subunit
      of neurofilaments and galanin. Immunohistochemical analysis combined with
      retrograde tracing method demonstrated that NPY-IR was detected in cutaneous and
      muscular sensory, but not in visceral sensory neurons. These findings suggest
      that NPY coexists with galanin in injured large type A cells, which may innervate
      the mechanoreceptors in the skin and muscle, such as corpuscles of Meissner and
      Pacini, or muscle spindles.

PMID- 7524051
TI  - Undifferentiated sarcoma of bone versus undifferentiated metastatic carcinoma--a
      diagnostic dilemma.

PMID- 7524050
TI  - Galanin induces opposite effects via different intracellular pathways in smooth
      muscle cells from dog colon.
AB  - Smooth muscle cells isolated by enzymatic digestion were used to determine the
      direct effects of galanin on circular and longitudinal muscle layers from dog
      proximal colon and to investigate the intracellular pathways involved in these
      effects. Effects of galanin were compared to those observed with other
      contracting [cholecystokinin octapeptide (CCK8)] and relaxing [vasoactive
      intestinal peptide (VIP)] agents. In longitudinal cells, galanin and CCK8 induced
      a contraction that was maximal at 1 nM galanin and 1 nM CCK8 and was 23.9 +/-
      4.5% and 23.4 +/- 3.4%, respectively, of the length of resting cells. Incubation
      of cells in Ca(2+)-free medium or in the presence of nifedipine caused an
      inhibition of galanin-induced contraction whereas it had no effect on the
      contraction induced by CCK8. Vasoactive intestinal peptide, forskolin, and 8
      bromo cAMP inhibited CCK-induced contraction but failed to inhibit contraction
      induced by galanin. The contraction induced by galanin was abolished; the CCK
      induced contraction was unchanged by pertussis toxin. In circular cells, CCK8
      induced a contraction that was maximal at 10 nM and was 24.2 +/- 2.6%. Galanin
      had no effect by itself. When cells were preincubated (1 min) with galanin (10 fM
      1 microM), the CCK8-induced contraction was inhibited, with a maximal effect at
      10 nM galanin. Likewise, VIP inhibited the CCK8-induced contraction with a
      maximal effect at 1 microM. Preincubation of cells with somatostatin, N
      ethylmaleimide, and (R)-p-cAMPS inhibited galanin- and VIP-induced relaxation. In
      conclusion, galanin induces a contraction of longitudinal smooth muscle cells
      that is dependent on an influx of extracellular calcium and an activation of
      pertussis toxin G-protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524045
TI  - Receptors for peptide YY and neuropeptide Y on guinea pig pancreatic acini.
AB  - We examined the effects of peptide YY (PYY), neuropeptide Y (NPY), and their
      analogues on dispersed pancreatic acini. Binding of [125I]PYY to acini was
      saturable, reversible, and specific, and PYY binding was best fit with a two-site
      model. The relative potencies for inhibiting [125I]PYY binding were PYY > or =
      NPY > NPY(13-36). There was no inhibition of binding with [Leu31,Pro34]NPY, PYX
      2, or pancreatic polypeptide. Both PYY and NPY (0.1 microM) inhibited amylase
      release stimulated by vasoactive intestinal polypeptide (VIP) (0.3 nM) and
      forskolin (1 microM) by about 30%, but not that stimulated by cholecystokinin-8
      or bombesin. The relative potencies for inhibiting VIP-stimulated amylase release
      were PYY > or = NPY > NPY(13-36), the same as those for inhibiting VIP-stimulated
      cAMP increase in acini. No inhibition was detected with [Leu31,Pro34]NPY. This
      work demonstrates Y2 receptors on guinea pig pancreatic acini mediating
      inhibitory actions of PYY and NPY on pancreatic enzyme secretion.

PMID- 7524053
TI  - Profiles of chicken macrophage effector functions.
AB  - In contrast to the mammalian system, avian species lack the so-called "resident"
      or "harvestable" macrophage population in the abdominal exudate. However,
      macrophages can be recruited into the chicken's abdominal cavity (presumably from
      the blood monocyte pool) if an inflammatory agent such as Sephadex is injected.
      The kinetics of inflammatory cell recruitment in terms of time, cell type, and
      state of activation to perform a particular effector function is currently an
      active area of research. This report will provide information on several chicken
      macrophage effector functions, including in vivo chemotaxis, phagocytosis,
      bacterial uptake and killing, biosynthesis of nitric oxide and various enzymes,
      and monokines such as interleukin-1 and granulocyte colony-stimulating factor.

PMID- 7524054
TI  - Influence of amylase genotypes on growth rate and feed conversion of chickens.
AB  - Chickens from two breeds were screened for amylase alleles designated as AmyF and
      AmyS to establish breeder flocks homozygous for each. Offspring from these flocks
      were then used to test the hypothesis that AmyF and AmyS amylases differ in their
      ability to digest cornstarch and wheat starch. The amylase allozymes were found
      to affect growth and feed conversion performance of the chickens, and the effects
      were more pronounced in one breed. However, these effects seemed to be more
      related to specific activity of the amylases than to starch source in the diet.
      The results indicate that in some breeds of chickens selection for AmyS may
      improve growth and feed efficiency performance.

PMID- 7524052
TI  - Prevalence of antibodies to hepatitis C virus after blood transfusion in heart
      surgery.
AB  - We studied the frequency and time of appearance of antibodies to the hepatitis C
      virus (HCV) retrospectively in the sera of 127 patients who underwent heart
      surgery between 1983 and 1986. They received blood from volunteer donors
      hepatitis B surface antigen (HBsAg) negative with normal serum alanine
      aminotransferase levels. A prospective follow-up was carried out every 15 days
      for at least 6 months from the moment of the transfusion. Of the ten patients who
      developed biochemical criteria of post-transfusional non-A non-B hepatitis, six
      seroconverted to anti-HCV (60%). Of the other 117, two were already positive
      before transfusion (1.51%), one patient showed antibodies only in the first post
      transfusional serum (passive transfer), and another two patients with no evidence
      of post-transfusional hepatitis developed HCV antibodies on the 90th day,
      remaining indefinitely (afterwards seroconversion without hepatitis); both
      patients' earlier sera were anti-HCV negative. Four (40%) of the ten patients
      with post-transfusional hepatitis did not develop any serum markers to known
      hepatotropic agents. Although these findings do not exclude a viral infection by
      these viruses, they are consistent with the involvement of an unidentified non-A,
      non-B, non-C agent.

PMID- 7524056
TI  - [Integrated approach to management of partial retardation in 5-8-year-old
      children].
AB  - The assessment of developmental retardation, of learning disabilities and their
      remediation are essential issues of psychosocial care. Depending on an
      Institution's destination, however, interpretation of such problems as well as
      their therapy may differ considerably. This is due to the diverse standards and
      specializations of the experts' professional training and experience, their
      individual meanings and institutional perspectives. In the first part a review of
      articles published in the last twenty years sums up the diagnostical and
      therapeutical concepts in the care for children with developmental retardation.
      The concepts are evaluated in terms of their practical relevance. In the second
      part the integrative concept of the Department of Child and Adolescent Psychiatry
      at Gottingen University is presented. A report of an evaluation study is added.
      The complexity of the subject is enhanced and the need not to look separately at
      the individual deficits but to consider the total intra- and interindividual
      relations.

PMID- 7524057
TI  - Screening maternal serum alpha-fetoprotein levels and human parvovirus
      antibodies.
AB  - The association between gestational infection with human parvovirus (B19) and
      fetal loss has increased interest in this virus and demand for diagnostic
      testing. However, serological assays for B19 are not yet widely available.
      Maternal serum alpha-fetoprotein (MSAFP) testing is commonly used during the
      second trimester to screen for various fetal defects. We attempted to determine
      whether an elevated level of MSAFP would be an appropriate indication for B19
      specific tests. Over a 26-month period, MSAFP tests were performed at Michigan
      State University for 21 392 women. Sera remaining after that testing were stored
      frozen. Of these, 22 cases samples--from women with MSAFP levels greater than 3.0
      multiples of the median (MOM) and pregnancies that ended in fetal loss--and 44
      matched control samples--from women with MSAFP levels greater than 0.4 and less
      than 2.2 MOM and live births at term--were tested for B19 antibodies. None of the
      66 samples was IgM positive, while 33 (50 per cent) were IgG positive. The
      presence of IgG was not significantly associated with case or control status
      (matched odds ratio = 0.77, 95 per cent confidence interval 0.28-2.11). These
      findings are consistent with other studies indicating prior infection in
      approximately half of adults and suggest that elevated screening MSAFP levels, in
      the absence of other evidence of B19 infection, should not prompt B19-specific
      testing.

PMID- 7524055
TI  - HPLC assay for FK 506 and two metabolites in isolated rat hepatocytes and rat
      liver microsomes.
AB  - Despite the current use of a standard two-step enzyme immunoassay in the clinical
      monitoring of the immunosuppressant FK 506, the lack of specificity for the
      parent drug in this assay renders it unsuitable for drug metabolism studies. An
      HPLC assay has been developed for studying the metabolism of FK 506 in isolated
      hepatocytes and microsomal mixtures. This assay allows simultaneous measurement
      of the parent drug and two of its time dependent metabolites. Metabolism of this
      drug was studied in intact rat liver cells and rat liver microsomes. We have
      shown that the metabolites observed are products of phase 1 oxidation reactions.
      Correlation of the 6 beta-testosterone hydroxylase activity with the FK 506
      metabolite (M1) initial formation rate is consistent with the belief that CYP 3A
      isozymes are involved in FK 506 metabolism in male rats.

PMID- 7524058
TI  - Prediction of an abnormal karyotype in fetuses with omphalocele.
AB  - The aim of this study was to assess the value of ultrasonographic evaluation in
      predicting abnormal karyotypes in fetuses with omphalocele. Forty fetuses with
      antenatally diagnosed omphalocele and available karyotype results were reviewed.
      Ultrasound evaluation included herniation contents and size, and the detection of
      other anomalies. Nine of 40 consecutive fetuses had abnormal karyotypes: trisomy
      18 (n = 5), trisomy 13 (n = 3), 47,XXX (n = 1). Only 1/25 with an extracorporeal
      liver versus 8/15 with an intracorporeal liver had abnormal chromosomes [P =
      0.0006, RR = 0.14 (0.02 < RR < 0.9)]. Small defects (< 3 cm) were associated with
      abnormal karyotypes [P = 0.01, RR = 4.7 (1.4 < RR < 15.6)]. Finding concurrent
      malformations was highly associated with chromosomal anomalies [P = 0.00004, RR =
      4.4 (2.3 < RR < 8.5)]. The presence of associated malformations, an
      intracorporeal liver, and a small herniation size are highly suggestive of an
      associated abnormal karyotype.

PMID- 7524059
TI  - Prenatal diagnosis of Roberts syndrome.

PMID- 7524061
TI  - [Laser and afterloading therapy].

PMID- 7524060
TI  - Endothelium-derived relaxing factor and cyclic GMP-dependent vasorelaxation in
      human chorionic plate arteries.
AB  - Endothelium derived relaxing factor (EDRF), now widely believed to be nitric
      oxide (NO), may play an important part in the control of fetoplacental vascular
      tone. To further explore this role we have determined the relaxation responses to
      exogenous NO and examined the temporal relationship between intracellular
      concentrations of cyclic GMP and vascular tone in isolated ring segments of human
      chorionic plate arteries. We have also determined the dose relations for the
      contractile agonists serotonin and the thromboxane analog U46619. Lastly, we have
      explored the relaxation responses to a wide range of agents known to elicit EDRF
      release in other vascular beds. Chorionic plate arteries relaxed significantly to
      exogenous NO with concomitant increases in cyclic guanosine monophosphate over
      basal values. ED50s for serotonin and U46619 were 1.48 x 10(-6) M and 3.39 x 10(
      8) M respectively. The ED50 for NO derived from S-nitroso-N-acetyl-penicillamine
      was 1.28 x 10(-6) M. Endothelium-intact segments of chorionic plate arteries pre
      contracted with either serotonin or U46619 failed to relax significantly to
      acetylcholine, adenosine diphosphate, A23187, bradykinin, and histamine and only
      minimally to substance P. We suggest that EDRF is likely to be important in the
      control of placental vascular tone, but that it is not possible to demonstrate
      its action in an unperfused experimental system.

PMID- 7524062
TI  - [Surgery of lung metastasis--indications, results and prognostic factors as an
      interdisciplinary concept].
AB  - Surgical therapy of lung metastases nowadays is an established procedure. The
      operation's purpose is the radical and therefore potential curative resection.
      Beside there are diagnostic and palliative indications. Beside there are
      diagnostic and palliative indications. Median sternotomy is the standard approach
      for revision of both lungs even in unilateral seeming disease. Preoperative
      staging is not reliable concerning number and extension of metastases. From 1972
      to 1991 843 operations for lung metastases were carried out in 729 patients in
      the surgical department of the "Thoraxklinik Heidelberg-Rohrbach". 30-day
      mortality amounted to 2.9%, 5-year-survival-rate was 33% overall from date of
      metastases resection. The best results were achieved in testicular cancer with
      67% 5-years-survival-rate, poorest survival was observed in melanomas with 12% 3
      years-survival. Beside the primary tumor and partly dependent on it several
      prognostic factors were relevant: radicality, sarcoma vs carcinoma in favour of
      carcinomas, disease-free interval, type of resection, thoracic lymphnode
      involvement. As figured out by multivariate analysis the prognostic influence of
      the factors varies considerably due to the kind of primary tumor. Surgery of lung
      metastases is part of an interdisciplinary oncological therapeutical concept and
      offers a prolonged survival to most of the patients and the possibility of cure
      to some. Even if prolongation of life is not feasible an improved quality and
      therefore a good palliation is obtained.

PMID- 7524066
TI  - Gastrin-releasing peptide stimulation of amylase release from rat pancreatic
      lobules involves intrapancreatic neurons.
AB  - Gastrin releasing peptide (GRP) immunoreactivity has been localized to nerve
      fibers innervating pancreatic acini and identified in nerve cell bodies within
      intrapancreatic ganglia. The role of intrapancreatic neurotransmission in GRP-
      and neuromedin C (NmC)-stimulated amylase release was investigated using rat
      pancreatic lobules in vitro. Lobule responsiveness to neuronal depolarization was
      demonstrated by amylase release upon exposure to 55 mM potassium (207 +/- 7% of
      control) or veratridine (294 +/- 12%). Both GRP and NmC produced dose-dependent
      increases in lobular amylase release, with ED50 values of 1.1 nM and 0.13 nM,
      respectively. Amylase release in response to submaximal concentrations of GRP
      were significantly inhibited by tetrodotoxin (78 +/- 5% of control) or
      hexamethonium (71 +/- 5% of control). GRP-stimulated amylase release was
      decreased to 71 +/- 5% of control by atropine coincubation. NmC-stimulated
      amylase release was not affected by tetrodotoxin, hexamethonium, or atropine. GRP
      (10(-10) to 10(-6) M) produced dose-dependent increments in [3H]acetylcholine
      release from pancreatic lobules. GRP stimulates amylase release from rat
      pancreatic lobules by a neurally mediated mechanism in addition to direct action
      on acinar membrane receptors.

PMID- 7524063
TI  - Expression of the ras-related rab3a gene in human insulinomas and normal human
      pancreatic islets.
AB  - To determine the expression of the small-molecular-weight guanosine 5'
      triphosphate (GTP)-binding protein rab3a in human endocrine pancreatic tissue,
      total RNA was isolated from five different human insulinomas and from normal
      human islets. The expression of rab3a was analyzed by Northern blots utilizing a
      1,300-bp Eco RI fragment of the cDNA coding for human rab3a. As in the brain, a
      specific transcript of 1,800 bp was detected in all insulinomas, though with
      varying signal intensity. When the northern membranes were rehybridized with a
      radioactively labeled insulin probe, a signal was found for all five insulinomas
      and cells of normal islets. In contrast, normal human islets showed no detectable
      expression of rab3a. In conclusion, rab3a is expressed to a significant degree in
      human insulinoma tissue but not in normal islets.

PMID- 7524065
TI  - Effect of a new cholecystokinin receptor antagonist (KSG 504) on the early stage
      of the healing process in acute pancreatitis induced in rats by the closed
      duodenal loop technique.
AB  - Creation of a closed duodenal loop produced edematous acute pancreatitis within 6
      h and hemorrhagic acute pancreatitis within 12 h in male Sprague-Dawley rats. The
      pancreatitis thus established tended to improve after releasing the loop. We
      investigated the effect of a new cholecystokinin receptor antagonist, KSG 504, on
      the healing process in edematous and hemorrhagic acute pancreatitis after
      releasing the loop. Serum amylase and lipase levels in the control group
      decreased gradually after releasing the loop, but the reductions were not
      significant. In both the group treated with KSG 504 intravenously and the group
      treated subcutaneously, serum amylase and lipase levels decreased markedly upon
      release of the loop in edematous acute pancreatitis. Furthermore, the histologic
      changes in edematous acute pancreatitis improved more rapidly than in the control
      group. However, no such biochemical or histologic evidence of improvement was
      observed in hemorrhagic acute pancreatitis. The new cholecystokinin receptor
      antagonist, KSG 504, displayed a therapeutic effect in edematous acute
      pancreatitis but not in hemorrhagic acute pancreatitis. These findings suggest
      that endogenous cholecystokinin release induced by the closed duodenal loop may
      have a contributory role in the development of edematous acute pancreatitis but
      not of hemorrhagic acute pancreatitis.

PMID- 7524067
TI  - Effect of 5-fluorouracil on secretion and synthesis of pancreatic digestive
      enzymes: studies in isolated pancreatic acini and perfused pancreas derived from
      normal rats and from rats with acute necrotizing pancreatitis.
AB  - 5-Fluorouracil (5-FU) has been claimed to have beneficial effects in human
      pancreatitis because of its ability to inhibit protein synthesis and secretion.
      However, the effect of 5-FU has not been studied in the pancreas of animals in
      more detail and the data in human pancreatitis are mostly derived from
      uncontrolled studies. Thus, we studied potential short-term effects of 5-FU on
      protein synthesis and secretion in isolated pancreatic acini from normal rats and
      from rats with sodium taurocholate-induced pancreatitis. Furthermore, we used the
      isolated perfused pancreas, damaged by taurocholate, to study whether arterial
      perfusion with 5-FU has any beneficial effects. When pancreatic acini were
      incubated with various concentrations of 5-FU, CCK-8-stimulated amylase secretion
      was not altered. Furthermore, 5-FU had no short-term effects on protein
      synthesis. Protein synthesis and secretion was already markedly depressed in
      isolated pancreatic acini derived from rats with sodium taurocholate-induced
      pancreatitis. 5-FU did not further decrease protein synthesis or secretion.
      Retrograde injection of sodium taurocholate in the main pancreatic duct of the
      isolated perfused pancreas resulted in a steep increase of amylase and lipase in
      the portal effluate. Arterial perfusion with 5-FU had no influence on enzyme
      release into the portal blood. We may conclude that our data, derived from
      experimental pancreatitis in rats, do not encourage investigation of the effect
      of 5-FU, an anticancer drug with possibly toxic side effects, in human
      pancreatitis.

PMID- 7524068
TI  - Immunohistochemistry analysis of platelet-derived growth factor A and B chains
      and platelet-derived growth factor alpha and beta receptor expression in benign
      prostatic hyperplasias and Gleason-graded human prostate adenocarcinomas.
AB  - The purpose of this study was to determine whether changes in the expression of
      platelet-derived growth factor (PDGF) and its receptors were associated with
      prostate cancer. Peroxidase-anti-peroxidase-immunoperoxidase labeling was used to
      detect the A and B chains and alpha and beta receptors of PDGF in 5 benign
      prostatic hyperplasias and 13 human prostate adenocarcinomas (Gleason grades 2 to
      9). In all 5 benign prostatic hyperplasias, none of the PDGF antibodies (even at
      high titers, 1:50 dilutions) labeled the epithelial or the stromal cells. In
      adenocarcinomas, the A chain and alpha receptor antibodies labeled both
      epithelial and stromal cells. The intensity of the staining was relatively high
      in low Gleason grade (<6) and low in high Gleason grade (>7) tissue; however, the
      B chain and beta receptor antibodies failed to label either epithelial or stromal
      cells in any of the 13 adenocarcinomas. The data suggest that PDGF A and alpha
      receptor genes may be preferentially turned on in epithelial and stromal prostate
      tumor cells.

PMID- 7524069
TI  - The use of digital cell image analysis of Feulgen-stained nuclei to
      quantitatively describe morphonuclear features in a series of 174 meningiomas.
AB  - The morphonuclear characteristics of 174 meningiomas were quantitatively
      described by means of the digital cell image analyses of Feulgen-stained nuclei.
      For this purpose, archival material, i.e., formalin-fixed paraffin-embedded
      pronase-digested tumors, was used. The present work specifically focuses on the
      morphonuclear features of angioblastic meningiomas to localize them with respect
      to classical as opposed to malignant meningiomas. The results show that
      angioblastic meningiomas, i.e., hemangioblastomas, have morphonuclear
      characteristics that are very similar to those of classical meningiomas, i.e.,
      meningotheliomatous, fibroblastic, transitional, angiomatous, and psammomatous
      types, and that are significantly distinct from those of malignant meningiomas.
      Malignant meningiomas, i.e., the hemangiopericytic and histologic features of
      malignancy types, are not only significantly different from classical meningiomas
      in their morphonuclear characteristics but are also very different among
      themselves. In conclusion, the quantitative description of chromatin features by
      means of digital cell image analyses confirms at the morphonuclear level the
      adherence of hemangioblastomas to the group of classical meningiomas, as
      suggested by the World Health Organization's histopathologic classification.

PMID- 7524064
TI  - Differential effects of a graded selective suppression of insulin secretion with
      galanin on glucose production and removal in dogs.
AB  - The metabolic response to graded decreases in insulin concentration was evaluated
      by measuring the concentration, production, and metabolic clearance rate of
      glucose in response to the infusion of different galanin doses (1-12
      micrograms/kg/h) in 18-h fasted dogs. Peripheral and portal concentrations of
      insulin and glucagon were measured simultaneously before, during, and after
      galanin infusions. No increases in portal or peripheral glucagon levels were seen
      at any dose of galanin infused but, in contrast, dose-dependent decreases of
      insulin levels occurred in both circulations. The metabolic clearance rate of
      glucose fell by approximately 25-30% at each dose of galanin infused; suggesting
      that the maximum effect was reached at the lowest dose. The rate of glucose
      production increased in a dose-dependent manner with integrated responses of 210
      +/- 170, 620 +/- 80, 1,330 +/- 440, 1,920 +/- 310, 1,940 +/- 170, and 1,970 +/-
      600 mg/kg at galanin doses of 1, 2, 4, 7, 10, and 12 micrograms/kg/h
      respectively; saturation of this response occurs at the 7 micrograms/kg/h dose of
      galanin. The changes in glucose production reflect most closely changes in the
      fractional decrease in insulin levels both in the portal and peripheral
      circulations. These changes appear to be mediated by insulin acting directly on
      the liver, because no alterations in the concentrations of the glucogenic
      substrates, lactate and glycerol, were seen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524070
TI  - Intravascular (angiotropic) large cell lymphoma: determination of monoclonality
      by polymerase chain reaction on paraffin-embedded tissues.
AB  - Angiotropic lymphoma is a rare, aggressive, intravascular non-Hodgkin's lymphoma,
      usually of B-cell phenotype. Because lymphoma is often clinically unsuspected,
      the small skin or muscle biopsies typically obtained for evaluation make
      assessment of lymphoid clonality through cell surface markers or Southern blot
      hybridization analysis difficult or impossible. The recent development of
      polymerase chain reaction methodologies to detect chromosomal translocations and
      immunoglobulin heavy chain gene rearrangement on paraffin-embedded tissue offers
      an attractive alternative for ascertaining the clonality of lymphoproliferative
      processes. We report a case of B-cell angiotropic lymphoma in which a monoclonal
      variable diversity joining region rearrangement of the immunoglobulin heavy chain
      locus was detected by polymerase chain reaction in both ante- and postmortem,
      formalin-fixed, paraffin-embedded skeletal muscle. The use of polymerase chain
      reaction in assessing clonality in angiotropic lymphoma is enhanced by the
      general absence of a background of reactive B-lymphoid cells in angiotropic
      lymphoma, which can obscure the monoclonal band and/or compromise sensitivity. No
      amplification product was obtained for t(14;18) involving the bcl-2 major
      breakpoint region. It is interesting to note that this case exhibited rare
      circulating lymphoma cells and more extensive bone marrow involvement (more than
      100 tumor cells/high magnification field) than has been previously described.

PMID- 7524071
TI  - Utility of Gomori methenamine silver stains in bronchoalveolar lavage specimens.
AB  - Bronchoalveolar lavage (BAL) with Gomori methenamine silver (GMS) stain is
      commonly used to detect Pneumocystis carinii and fungal organisms as causes of
      infectious pulmonic disease in immunosuppressed patients. However, several
      reports have indicated that GMS stains are not any more sensitive than
      conventional cytologic stains in detecting Pneumocystis organisms in select
      patient populations, such as those with acquired immunodeficiency syndrome
      (AIDS). To examine the utility of GMS stains in our laboratory, we
      retrospectively reviewed 243 BALs from 188 patients. Sensitivity of the GMS stain
      for Pneumocystis and for fungi detection was 100%. Sensitivity for Pneumocystis
      and for fungi detection by Papanicolaou stain alone was 79% and 88%,
      respectively; by Diff-Quik stain alone it was 68% and 88%, respectively; and by
      combined Papanicolaou and Diff-Quik stains it was 79% and 100%, respectively. In
      four additional cases, fungi were detected by other methods (culture, biopsy) and
      not by BAL. The GMS stain result was correlated with a number of risk variables
      to determine which variables were associated with GMS positivity. Using stepwise
      logistic regression, Pneumocystis positivity by GMS stain correlated (P < 0.0001)
      only with the variable of history of AIDS or AIDS risk factors. Fungal organism
      positivity by GMS stain correlated (P = 0.02) only with the variable of history
      of BAL positivity for fungus. Cost savings analyses were performed, estimating
      the cost of the GMS stain at $45 (total cost of GMS in 243 BALs was
      $10,935).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524072
TI  - Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves
      predictions of RNA folding.
AB  - An RNA model system consisting of an oligomer binding to a 4-nt overhang at the
      5' end of a hairpin stem provides thermodynamic parameters for helix-helix
      interfaces. In a sequence-dependent manner, oligomers bind up to 1000-fold more
      tightly adjacent to the hairpin stem than predicted for binding to a free
      tetramer at 37 degrees C. For the interface (/) in [formula: see text] additional
      free energy change, delta delta G 37 degrees, for binding is roughly the nearest
      neighbor delta G 37 degrees for propagation of an uninterrupted helix of
      equivalent sequence, CGGC. When X and Z are omitted, the delta delta 37 degrees
      is even more favorable by approximately 1 kcal/mol (1 cal = 4.184J). On average,
      predictions of 11 RNA secondary structures improve from 67 to 74% accuracy by
      inclusion of similar stacking contributions.

PMID- 7524073
TI  - A tRNA-like structure is present in 10Sa RNA, a small stable RNA from Escherichia
      coli.
AB  - We have determined that 10Sa RNA (one of the small stable RNAs found in
      Escherichia coli) has an interesting structural feature: the 5' end and the 3'
      end of 10Sa RNA can be arranged in a structure that is equivalent to a half
      molecule (acceptor stem and TFC stem-loop) of alanine tRNA of E. coli. Primer
      extension analysis of 10Sa RNA extracted from a bacterial mutant with temperature
      sensitive RNase P function revealed that the precursor to 10Sa RNA (pre-10Sa RNA)
      is folded into a pre-tRNA-like structure in vivo such that it can be cleaved by
      RNase P to generate the 5' end of the mature 10Sa RNA. The purified 10Sa RNA can
      be charged with alanine in vitro. Disruption of the gene encoding 10Sa RNA (ssrA)
      caused a reduction in the rate of cell growth, which was especially apparent at
      45 degrees C, and a reduction in motility on semisolid agar. These phenotypic
      characteristics of the deletion strain (delta ssrA) allowed us to investigate the
      effects of some mutations in 10Sa RNA in vivo, although the exact function of
      10Sa RNA still remains unclear. When the G.U pair (G3.U357) in 10Sa RNA, which
      may be equivalent to the determinant G.U pair of alanine tRNA, was changed to a
      G.A or G.C pair, the ability to complement the phenotypic mutations of the delta
      ssrA strain was lost. Furthermore, this inability to complement the mutant
      phenotypes that was caused by the substitution of the determinant bases by a G.A
      pair could be overcome by the introduction of a gene encoding alanyl-tRNA
      synthetase (alaS) on a multicopy plasmid. The evidence suggests that the proposed
      structural features of 10Sa RNA are indeed manifested in vivo.

PMID- 7524075
TI  - CD28 is associated with and induces the immediate tyrosine phosphorylation and
      activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell
      line.
AB  - T lymphocytes require two signals to be activated. The antigen-specific T-cell
      receptor can deliver the first signal, while ligation of the T-cell surface
      molecule CD28 by antibodies or its cognate ligands B7-1 (CD80) or B7-2 has been
      demonstrated to be sufficient for the delivery of the second signal. Signaling
      via CD28 and the T-cell receptor results (i) in their costimulation of T cells to
      produce numerous lymphokines including interleukin 2 and (ii) in the prevention
      of anergy induction. Little is known about the pathway by which CD28 mediates its
      signals except that protein-tyrosine phosphorylation is involved. We show here in
      human Jurkat cells that the Tec-family protein-tyrosine kinase ITK/EMT
      (p72ITK/EMT) is associated with CD28 and becomes tyrosine-phosphorylated and
      activated within seconds of CD28 ligation. This tyrosine phosphorylation of
      p72ITK/EMT is rapid (within 30 sec), occurs in the absence of LCK activation, and
      precedes tyrosine phosphorylation of the guanine nucleotide exchange factor VAV.
      Secondary crosslinking of CD28 is unnecessary for the induced tyrosine
      phosphorylation of p72ITK/EMT. Thus, tyrosine phosphorylation of p72ITK/EMT may
      represent one of the earliest events in CD28 signaling. This demonstrates that a
      member of the Tec family of protein tyrosine kinases, similar to members of the
      Src and Syk families, plays a role in the activation of T cells. Furthermore, the
      data demonstrate that p72ITK/EMT, and by analogy other members of the Tec family,
      responds to extracellularly generated signals.

PMID- 7524074
TI  - Ligand-induced formation of nucleic acid triple helices.
AB  - We demonstrate that ligand binding can be used to induce the formation of triplex
      structures that would not otherwise form. Specifically, we show that binding of
      berenil or 4',6-diamidino-2-phenylindole DAPI) induces formation of the
      poly(rA).poly(rA).poly(dT) triplex, providing an example of an
      RNA(purine).RNA(purine).DNA(pyrimidine) triplex. We also show that binding of
      berenil, DAPI, ethidium, or netropsin can induce formation of the
      poly(dT).poly(rA).poly(dT) triplex, thereby overcoming a practical limitation to
      the formation of DNA.RNA.DNA triplexes with a purine RNA strand. Based on the
      enhanced thermal stabilities of the drug-bound poly(dT).poly(rA).poly(dT)
      complexes at 18 mM Na+, we define the relative triplex-inducing efficiencies of
      these four ligands to be: berenil > DAPI > ethidium > netropsin. Our results
      demonstrate that ligand binding can be used to induce the formation of triplex
      structures that do not form in the absence of the ligand. This triplex-inducing
      capacity has potentially important implications in the design of novel antisense,
      antigene, and diagnostic strategies.

PMID- 7524076
TI  - Definition of a human suppressor T-cell epitope.
AB  - The quality of the response produced by regulatory or helper T (Th) cells
      presently receives much attention because of its possible implications for
      vaccine development and immunomodulation. Apart from cytokines and so-called
      costimulatory signals, antigens and the presenting major histocompatibility
      complex (MHC) molecules may play a role in determining the type of T-cell
      response generated toward antigens. To examine the role of antigen and/or HLA in
      control of T-cell subset activation, we have studied a special case, namely CD4+
      suppressor T (Ts) cells in leprosy. Mycobacterium leprae-induced Ts cell clones
      have been previously isolated from peripheral blood and skin lesions of
      lepromatous leprosy patients and were shown to specifically down-regulate
      mycobacterium-specific Th cell responses. Despite considerable effort, the
      antigens recognized by these Ts cells have thus far not been identified. Here we
      report that all HLA-DR2-restricted CD4+ Ts cell clones derived from a lepromatous
      leprosy patient recognize an epitope that maps between the amino acid residues
      439 and 448 of the mycobacterial hsp65. The peptide was presented to these Ts
      cells by HLA-DRB1*1503, a recently discovered HLA-DR2 variant. Non-suppressor T
      cell clones derived from the same patient recognized antigens other than the
      hsp65 and were also stimulated by other HLA-DR2 variants. In independent cloning
      experiments peptide 435-449 and recombinant hsp65 induced exclusively Ts cells in
      this lepromatous leprosy patient. The Ts clones recognizing this particular
      epitope were derived from at least seven different progenitors, as they expressed
      different T-cell receptor alpha and beta chains. Thus, our data indicate that a
      specific peptide-HLA class II combination may exclusively activate Ts cells.

PMID- 7524077
TI  - High rate of mismatch extension during reverse transcription in a single round of
      retrovirus replication.
AB  - We made spleen necrosis virus-based retroviral vectors with mutations at the 3'
      end of the primer binding site region to observe the effects of terminal
      mismatches on retroviral replication. These vectors, when compared to a vector
      with the wild-type primer binding sequence, allowed us to assay the effects of
      the mutations on the viral titer during a single cycle of replication. The mutant
      vectors had titers that were comparable to the wild-type vector, indicating that
      reverse transcriptase has no trouble extending mismatches of as many as 3 bases
      under normal in vivo conditions. These results confirm and extend previous in
      vitro studies [Yu, H. & Goodman, M. (1992) J. Biol. Chem. 15, 10888-10896] that
      showed that such mismatch extension could occur in a cell-free system at high
      concentrations of incorrect nucleotides and in the absence of correct
      nucleotides. We now show that mismatch extension can occur during normal
      retroviral replication in cells and at normal physiological nucleotide
      concentrations.

PMID- 7524078
TI  - Electrostatic distance geometry in a K+ channel vestibule.
AB  - Many voltage-gated K+ channels carry in the external vestibule a receptor for
      charybdotoxin, a peptide channel blocker. We use point mutagenesis of both
      charybdotoxin and a Shaker K+ channel to isolate the electrostatic interaction
      energy between chosen pairs of residues, one on the channel and one on bound
      toxin. The results allow estimates of physical distances between such residue
      pairs and, in combination with the known structure of charybdotoxin, localize
      specific channel residues in three-dimensional space.

PMID- 7524079
TI  - Temporal differences in the activation of three classes of non-transmembrane
      protein tyrosine kinases following B-cell antigen receptor surface engagement.
AB  - We evaluated in WEHI 231 B cells the time-dependent responses of Lyn, Blk, Btk,
      Syk, and three members of the Jak family of protein tyrosine kinases following
      antibody-mediated surface engagement of the B-cell antigen receptor. Our results
      show that the enzyme activities of Lyn and Blk were stimulated within seconds of
      antigen receptor engagement and correlated with the initial tyrosine
      phosphorylation of the Ig alpha and Ig beta subunits of the B-cell antigen
      receptor. Btk enzyme activity was also transiently stimulated and was maximal at
      approximately 5 min after B-cell receptor surface binding. Syk activity gradually
      increased to a maximum at 10-30 min following receptor ligation and was found to
      parallel the association of Syk with the tyrosine phosphorylated Ig alpha and Ig
      beta subunits of the receptor. While the specific activities of the Jak1, Jak2,
      and Tyk2 protein tyrosine kinases were unaltered following B-cell receptor
      ligation, the abundance of Jak1 and Jak2 were increased 3- to 4-fold within 10
      min of receptor engagement. These results demonstrate that multiple families of
      non-transmembrane protein tyrosine kinases are temporally regulated during the
      process of B-cell antigen receptor-initiated intracellular signal transduction.

PMID- 7524080
TI  - Coupling of RNA displacement and intrinsic termination in transcription from
      synthetic RNA.DNA bubble duplex constructs.
AB  - Functional transcription elongation complexes can be formed by adding RNA
      polymerase in trans to a preformed nucleic acid construct. This construct
      consists of a double-stranded DNA fragment that contains a noncomplementary
      (permanent DNA bubble) region into which an RNA primer oligonucleotide has been
      hybridized. By ligating a DNA fragment containing the strong intrinsic terminator
      T7Te to the RNA.DNA bubble duplex, we show here that Escherichia coli core RNA
      polymerase-catalyzed transcription, initiated from such a construct, terminates
      at the predicted position. Furthermore, we show that the termination efficiency
      obtained is comparable to that observed in a control reaction initiated with the
      E. coli holopolymerase from the T7A1 promoter if an RNA oligomer trap is used to
      permit proper displacement of the nascent RNA from the DNA template strand. The
      trap oligomer is complementary to the template strand of the permanent DNA bubble
      and prevents rehybridization of the nascent RNA at this site. Varying the amount
      of RNA trap that is added permits us to modulate the extent of total RNA
      displacement. Our results show that RNA displacement and termination efficiency
      are directly correlated, suggesting that intrinsic termination requires that the
      nascent RNA be free to assume its solution conformation. Several models of
      intrinsic termination are presented and discussed in light of these data.

PMID- 7524081
TI  - Role of interferon alpha/beta receptor chain 1 in the structure and transmembrane
      signaling of the interferon alpha/beta receptor complex.
AB  - A previously cloned cDNA encodes one subunit of the human interferon alpha/beta
      receptor (IFN alpha R), denoted IFN alpha R1. To study the expression and
      signaling of IFN alpha R1, we used monoclonal antibodies (mAbs) generated against
      the baculovirus-expressed ectodomain of IFN alpha R1. Immunoprecipitation and
      immunoblotting of lysates from a variety of human cell lines showed that IFN
      alpha R1 has an apparent molecular mass of 135 kDa. Binding analysis with 125I
      labeled mAb demonstrated high levels of cell surface expression of IFN alpha R1
      in human cells and in mouse cells transfected with IFN alpha R1 cDNA, whereas no
      cross-reactivity was observed in control mouse L929 cells expressing only the
      endogenous mouse receptor. The subunit was rapidly down-regulated by IFN alpha
      (80% decrease within 2 hr) and degraded upon internalization. The IFN alpha R1
      chain appeared to be constitutively associated with the 115-kDa subunit of the
      IFN alpha/beta receptor, since the mAbs coprecipitated this protein. IFN
      alpha/beta treatment induced tyrosine phosphorylation of IFN alpha R1 within 1
      min, with kinetics paralleling that of the IFN-activated protein-tyrosine kinases
      Jak1 and Tyk2. Ligand-induced tyrosine phosphorylation of IFN alpha R1 was
      blocked by the kinase inhibitors genistein or staurosporine. Although IFN alpha
      R1 cDNA-transfected mouse cells expressed high levels of this subunit when
      compared with empty vector-transfected cells the number of binding sites for
      human IFN alpha (50-75 sites per cell) was not increased. Human IFN alpha induced
      the expression of a mouse IFN alpha/beta-responsive gene (the 204 gene) in mouse
      L929 cells transfected with the IFN alpha R1 cDNA, but not in mock-transfected
      cells. These results suggest that the IFN alpha R1 subunit acts as a species
      specific signal transduction component of the IFN alpha/beta receptor complex.

PMID- 7524082
TI  - Constitutive and inducible nitric oxide synthase gene expression, regulation, and
      activity in human lung epithelial cells.
AB  - Histochemical activity and immunoreactivity of nitric oxide synthase (NOS, EC
      1.14.13.39) have been recently demonstrated in human lung epithelium. However,
      the molecular nature of NOS and the regulation and function of the enzyme(s) in
      the airway is not known. A549 cells (human alveolar type II epithelium-like),
      BEAS 2B cells (transformed human bronchial epithelial cells), and primary
      cultures of human bronchial epithelial cells all exhibited constitutive NOS
      activity that was calcium dependent and inhibitable by the NOS inhibitor NG
      monomethyl-L-arginine. Nitric oxide production by epithelial cells was enhanced
      by culture in the presence of interferon gamma, interleukin 1 beta, tumor
      necrosis factor alpha, and lipopolysaccharide; the NOS activity expressed under
      these conditions showed less dependence on calcium, reminiscent of other
      inducible forms of NOS. Two distinct NOS mRNA species, homologous to previously
      identified constitutive brain (type I) and inducible hepatic (type II) NOS, were
      demonstrated by reverse transcription-polymerase chain reaction in all cell
      lines. Northern analysis confirmed the expression of inducible NOS mRNA. Cell
      culture with epidermal growth factor, a principal regulator of epithelial cell
      function, decreased inducible NOS activity by posttranscriptional action but did
      not affect constitutive NOS activity. The coexistence of constitutive and
      inducible NOS in human alveolar and bronchial epithelial cells is consistent with
      a complex mechanism evolved by epithelial cells to protect the host from
      microbial assault at the air/surface interface while shielding the host from the
      induction of airway hyperreactivity.

PMID- 7524083
TI  - Classification of hepatitis C viruses based on phylogenetic analysis of the
      envelope 1 and nonstructural 5B regions and identification of five additional
      subtypes.
AB  - Genotyping of hepatitis C virus-positive sera by means of a line probe assay
      indicated that < 3% of European samples, but up to 30% of Gabonese sera, could
      not be classified as either 1a, 1b, 2a, 2b, 3a, 3b, 4c, 5a, or 6a. Such samples
      were analyzed in the 5' untranslated region and in the nonstructural 5 (NS5)
      region. Classification based on phylogenetic analysis of the commonly used 222-bp
      long NS5B region was possible for most but not all of the selected sera.
      Therefore, the core/envelope 1 region (579 bp) and a larger NS5B (340 bp) region
      were also analyzed. Only the phylogenetic analysis of the 340-bp NS5B region of
      these newly identified and published isolates provided unambiguous classification
      into types and subtypes. Furthermore, unequivocal evidence for four subtypes in
      type 2 and eight subtypes in type 4 was provided. A specific recognition sequence
      in the 5' untranslated region was observed for every newly identified subtype.
      Based on 1830 pair-wise comparisons in NS5B, isolates belonging to the same
      subtype showed evolutionary distances of < 0.127 and isolates of the same type
      exhibited evolutionary distances of < 0.328. These phylogenetic border distances
      can be conveniently used for classification of hepatitis C virus isolates into
      types and subtypes.

PMID- 7524085
TI  - Recombinant adeno-associated virus (rAAV)-mediated expression of a human gamma
      globin gene in human progenitor-derived erythroid cells.
AB  - Effective gene therapy for the severe hemoglobin (Hb) disorders, sickle-cell
      anemia and thalassemia, will require an efficient method to transfer, integrate,
      and express a globin gene in primary erythroid cells. To evaluate recombinant
      adeno-associated virus (rAAV) for this purpose, we constructed a rAAV vector
      encoding a human gamma-globin gene (pJM24/vHS432A gamma). Its 4725-nucleotide
      genome consists of two 180-bp AAV inverted terminal repeats flanking the core
      elements of hypersensitive sites 2, 3, and 4 from the locus control region of the
      beta-globin gene cluster, linked to a mutationally marked A gamma-globin gene (A
      gamma) containing native promoter and RNA processing signals. CD34+ human
      hematopoietic cells were exposed to rAAV particles at a multiplicity of infection
      of 500-1000 and cultured in semisolid medium containing several cytokines. A
      reverse transcriptase polymerase chain reaction assay distinguished mRNA signals
      derived from transduced and endogenous human gamma-globin genes. Twenty to 40% of
      human erythroid burst-forming unit-derived colonies expressed the rAAV-transduced
      A gamma-globin gene at levels 4-71% that of the endogenous gamma-globin genes.
      The HbF content of pooled control colonies was 26%, whereas HbF was 40% of the
      total in pooled colonies derived from rAAV transduced progenitors. These data
      establish that rAAV containing elements from the locus control region linked to a
      gamma-globin gene are capable of transferring and expressing that gene in primary
      human hematopoietic cells resulting in a substantial increase in HbF content.

PMID- 7524084
TI  - Cloning of the cDNA for a hematopoietic cell-specific protein related to CD20 and
      the beta subunit of the high-affinity IgE receptor: evidence for a family of
      proteins with four membrane-spanning regions.
AB  - We report the cloning of the cDNA for a human gene whose mRNA is expressed
      specifically in hematopoietic cells. A long open reading frame in the 1.7-kb mRNA
      encodes a 214-aa protein of 25 kDa with four hydrophobic regions consistent with
      a protein that traverses the membrane four times. To reflect the structure and
      expression of this gene in diverse hematopoietic lineages of lymphoid and myeloid
      origin, we named the gene HTm4. The protein is about 20% homologous to two other
      "four-transmembrane" proteins; the B-cell-specific antigen CD20 and the beta
      subunit of the high-affinity receptor for IgE, Fc epsilon RI beta. The highest
      homologies among the three proteins are found in the transmembrane domains, but
      conserved residues are also recognized in the inter-transmembrane domains and in
      the N and C termini. Using fluorescence in situ hybridization, we localized HTm4
      to human chromosome 11q12-13.1, where the CD20 and Fc epsilon RI beta genes are
      also located. Both the murine homologue for CD20, Ly-44, and the murine Fc
      epsilon RI beta gene map to the same region in murine chromosome 19. We propose
      that the HTm4, CD20, and Fc epsilon RI beta genes evolved from the same ancestral
      gene to form a family of four-transmembrane proteins. It is possible that other
      related members exist. Similar to CD20 and Fc epsilon RI beta, it is likely that
      HTm4 has a role in signal transduction and, like Fc epsilon RI beta, might be a
      subunit associated with receptor complexes.

PMID- 7524086
TI  - Stimulation of glycogen synthesis by insulin in human erythroleukemia cells
      requires the synthesis of glycosyl-phosphatidylinositol.
AB  - Although the insulin-dependent hydrolysis of glycosyl-phosphatidylinositol (GPI)
      may play an important role in insulin action, an absolute requirement for this
      glycolipid has not been demonstrated. Human K562 cells were mutated to produce a
      cell line (IA) incapable of the earliest step in PI glycosylation, the formation
      of PI-GlcNAc. Another cell line (IVD) was deficient in the deacetylation of PI
      GlcNAc to form PI-GlcN and subsequent mannosylated species. Each line was
      transfected with wild-type human insulin receptors. Similar insulin-stimulated
      receptor autophosphorylation was observed in all three lines, along with a nearly
      identical increase in the association of phosphorylated insulin receptor
      substrate 1 with endogenous PI 3-kinase. Both normal and GPI-defective lines also
      displayed a similar 2- to 3-fold increase in phosphorylation of the Shc protein
      and its association with growth factor receptor-bound protein 2 in response to
      insulin. In contrast to these results, striking differences were noted in insulin
      stimulated glycogen synthesis. In normal cells, glycogen synthesis was
      significantly increased by insulin, whereas no insulin stimulation was observed
      in GPI-deficient IA cells, and only a trace of stimulation was detected in IVD
      cells. These results indicate that tyrosine phosphorylation produced by insulin
      is not dependent on GPI synthesis, and this effect is not sufficient to elicit at
      least some of the metabolic effects of the hormone. In contrast, GPI synthesis is
      required for the stimulation of glycogen synthesis by insulin in these cells.
      These findings support the existence of divergent pathways in the action of
      insulin.

PMID- 7524087
TI  - Epidermal expression of intercellular adhesion molecule 1 is not a primary
      inducer of cutaneous inflammation in transgenic mice.
AB  - Keratinocytes at sites of cutaneous inflammation have increased expression of
      intercellular adhesion molecule 1 (ICAM-1), a cytokine-inducible adhesion
      molecule which binds the leukocyte integrins LFA-1 and Mac-1. Transgenic mice
      were prepared in which the expression of mouse ICAM-1 was targeted to basal
      keratinocytes by using the human K14 keratin promoter. The level of constitutive
      expression attained in the transgenic mice exceeded the peak level of ICAM-1
      expression induced on nontransgenic mouse keratinocytes in vitro by optimal
      combinations of interferon gamma and tumor necrosis factor alpha or in vivo by
      proinflammatory stimuli such as phorbol 12-myristate 13-acetate. In vitro
      adhesion assays demonstrated that cultured transgenic keratinocytes were superior
      to normal keratinocytes as a substrate for the LFA-1-dependent binding of mouse T
      cells, confirming that the transgene-encoded ICAM-1 was expressed in a functional
      form. However, the high level of constitutive ICAM-1 expression achieved on
      keratinocytes in vivo in these transgenic mice did not result in additional
      recruitment of CD45+ leukocytes into transgenic epidermis, nor did it elicit
      dermal inflammation. Keratinocyte ICAM-1 expression also did not potentiate
      contact-hypersensitivity reactions to epicutaneous application of haptens. The
      absence of a spontaneous phenotype in these transgenic mice was not the result of
      increased levels of soluble ICAM-1, since serum levels of soluble ICAM-1 were
      equal in transgenic mice and controls. We conclude that elevated ICAM-1
      expression on keratinocytes cannot act independently to influence leukocyte
      trafficking and elicit cutaneous inflammation.

PMID- 7524089
TI  - Enzymatic completion of mammalian lagging-strand DNA replication.
AB  - Using purified proteins from calf and a synthetic substrate, we have
      reconstituted the enzymatic reactions required for mammalian Okazaki fragment
      processing in vitro. The required reactions are removal of initiator RNA,
      synthesis from an upstream fragment to generate a nick, and then ligation. With
      our substrate, RNase H type I (RNase HI) makes a single cut in the initiator RNA,
      one nucleotide 5' of the RNA-DNA junction. The double strand specific 5' to 3'
      exonuclease removes the remaining monoribonucleotide. After dissociation of
      cleaved RNA, synthesis by DNA polymerase generates a nick, which is then sealed
      by DNA ligase I. The unique specificities of the two nucleases for primers with
      initiator RNA strongly suggest that they perform the same reactions in vivo.

PMID- 7524090
TI  - The nodulation-signaling protein NodO from Rhizobium leguminosarum biovar viciae
      forms ion channels in membranes.
AB  - The secreted nodulation-signaling protein NodO was purified from the supernatant
      of cultures of Rhizobium leguminosarum biovar viciae. The native protein has a
      M(r) of approximately 67,000, suggesting that it exists as a dimer since the DNA
      sequence predicts a M(r) of 30,002. Pure NodO protein had no protease, pectinase,
      or cellulase activity, and no binding was observed to lipooligosaccharide
      nodulation factors. Although NodO is relatively hydrophilic, it appeared to
      insert into liposomes and was protected by liposomes from proteolytic cleavage.
      When added to planar lipid bilayers, NodO formed cation-selective channels that
      allowed the movement of monovalent cations (K+ and Na+) across the membrane. NodO
      is a Ca(2+)-binding protein; in the presence of high concentrations of Ca2+,
      channel activity was reduced. We hypothesize that NodO plays a role in nodulation
      signaling by stimulating uptake of nodulation factors or by forming cation
      specific channels that function synergistically with the proposed
      lipooligosaccharide-induced depolarization of the plasma membrane of leguminous
      plants.

PMID- 7524088
TI  - Molecular cloning of a functional human galanin receptor.
AB  - The ubiquitous neuropeptide galanin controls numerous functions such as endocrine
      secretions, intestinal motility, and behavioral activities. These regulatory
      effects of galanin are mediated through the interaction with specific membrane
      receptors and involve the pertussis toxin-sensitive guanine nucleotide binding
      proteins Gi/Go as transducing elements. We report here the isolation of a cDNA
      coding for a human galanin receptor from a Bowes melanoma cell line cDNA
      expression library, by using a radioligand binding strategy. The nucleotide
      sequence of the cloned receptor reveals an open reading frame encoding a 349
      amino acid protein with seven putative hydrophobic transmembrane domains and
      significant homology with members of the guanine nucleotide binding protein
      coupled neuropeptide receptor family. The cloned receptor expressed in COS cells
      specifically binds human, porcine, and rat galanin with high affinity (Kd in the
      nanomolar range) and mediates the galanin inhibition of adenylate cyclase. A 2.8
      kb galanin receptor transcript was identified in several human tissues. Cloning
      of this galanin receptor should enhance our knowledge of its distribution,
      structure, and function in human physiology and pathophysiology.

PMID- 7524091
TI  - Proteolytic action of thrombin is required for electrical activity-dependent
      synapse reduction.
AB  - Molecular mechanisms of activity-dependent synapse reduction were studied in an
      in vitro mammalian neuromuscular preparation. Synapse reduction in this model is
      activity-dependent and is substantially reduced by the broad-spectrum protease
      inhibitor, leupeptin, suggesting the role of activity-dependent proteolytic
      action in the process. Our present experiments show that a potent and specific
      thrombin inhibitor, hirudin, at nanomolar concentration completely blocked the
      activity-dependent synapse reduction. Furthermore, a naturally occurring serine
      protease inhibitor, protease nexin I (PNI), which closely colocalizes with
      acetylcholine receptors at the neuromuscular junction, inhibited the synapse
      reduction at the same low concentration. In contrast, neither cystatin, a
      cysteine protease inhibitor, nor aprotinin, a serine protease inhibitor that does
      not inhibit thrombin, blocked the synapse reduction. Similarly, neither of the
      inhibitors of the calcium-activated proteases calpain I and II prevented the
      reduction of synapses. These results strongly suggest that serine proteolytic
      action by thrombin or thrombin-like molecules is required for synapse reduction
      in our in vitro model of the mammalian neuromuscular junction.

PMID- 7524092
TI  - Disproportionate growth in mice with Igf-2 transgenes.
AB  - Injection transgenesis was used to study the long-term effects of excess insulin
      like growth factor II on mouse growth and differentiation. By using a construct
      in which the coding region of the mouse insulin like growth factor II gene (Igf
      2) was placed under the control of a keratin gene promoter, four transgenic lines
      were established, all of which displayed overgrowth of the skin as judged by
      wrinkling. In addition to high levels of expression in the skin, transgene
      transcripts were also present in the alimentary canal and uterus. At most of the
      sites of transgene expression the cell number (DNA content) was greatly
      increased, indicating a local action of the excess insulin-like growth factor II
      on cell multiplication. Adult total live weight was slightly increased and there
      was no macroscopic evidence of tumor formation. The characteristics of these
      transgenic mice indicate distinct local and systemic actions for insulin-like
      growth factor II.

PMID- 7524093
TI  - Galanin-containing neurons in the paraventricular nucleus: a neurochemical marker
      for fat ingestion and body weight gain.
AB  - The physiological function of the peptide galanin (Gal) remains to be
      established. It is known to exist in high concentrations within the hypothalamus
      and to modulate the secretion of specific hormones, as well as to potentiate food
      consumption. Our study provides evidence for an essential function of neuronal
      Gal, within a specific hypothalamic area, in stimulating the behavioral process
      of fat ingestion and body weight gain. Through analyses of peptide levels via RIA
      and of gene expression via in situ hybridization, a close positive association is
      established between Gal in the paraventricular nucleus (PVN), particularly its
      midlateral region, and fat ingestion. No such relationship is detected for Gal in
      other brain areas or between PVN Gal and ingestion of carbohydrate or protein,
      supporting the behavioral and anatomical specificity of this relationship.
      Through PVN injection studies with antisense oligonucleotides to Gal mRNA, a
      dramatic decline in fat ingestion and body weight suggests that endogenous Gal
      contributes to the natural appetite for fat. Thus, Gal in the PVN is identified
      as a neurochemical marker for fat ingestion and, consequently, body weight gain.

PMID- 7524094
TI  - Lymphocyte antigen receptor activation of a focal adhesion kinase-related
      tyrosine kinase substrate.
AB  - One of the earliest responses of T and B lymphocytes to stimulation through their
      antigen receptors is the activation of protein tyrosine kinases and the tyrosine
      phosphorylation of multiple cellular substrates. Here we describe a tyrosine
      kinase substrate, fakB, a putative homologue of the focal adhesion kinase
      pp125FAK. Tyrosine phosphorylation of fakB was rapidly augmented in human T and B
      cells following antigen receptor cross-linking with antibody, while pp125FAK was
      nonresponsive. Costimulation of the T-cell antigen receptor (TCR/CD3) with either
      the CD2 or CD4 costimulatory receptors induced synergistic fakB tyrosine
      phosphorylation in normal human T cells. Engagement of TCR/CD3 induced the stable
      association of fakB with ZAP-70, the TCR/CD3 sigma-chain-associated tyrosine
      kinase involved in antigen receptor-induced T-cell activation. In addition,
      preformed complexes of fakB and ZAP-70 were observed in T-cell leukemia lines.
      Phosphorylation of fakB on serine, threonine, and tyrosine residues was observed
      both in vivo and in vitro, where a functional increase of in vitro kinase
      activity was observed following TCR/CD3 stimulation. fakB is thus a focal
      adhesion kinase-related tyrosine kinase substrate that is differentially
      regulated from that of pp125FAK and likely plays a role in antigen-induced
      lymphocyte signaling.

PMID- 7524095
TI  - Heme coordination of NO in NO synthase.
AB  - A current question in nitric oxide (NO) biology is whether NO can act as a
      feedback inhibitor of NO synthase (NOS). We have approached this problem by
      examining the interaction of NO with neuronal NOS by optical absorption and
      resonance Raman scattering spectroscopies. Under an inert atmosphere NO
      coordinated to the heme iron in both the oxidized and reduced forms of NOS. The
      Soret and visible optical absorption transitions are detected at 436 and at 567
      nm, respectively, in the Fe(2+)-NO heme complex and at 440 nm and at 549 and 580
      nm, respectively, in the Fe(3+)-NO heme complex. In the resonance Raman spectrum
      of the ferrous complex the Fe-NO stretching mode is located at 549 cm-1 in the
      presence of L-arginine and at 536 cm-1 in the absence of L-arginine, whereas in
      the ferric enzyme the mode is located at 540 cm-1 (in the absence of L-arginine).
      The interaction between bound L-arginine and the NO indicates that L-arginine
      binds directly over the heme just as do the substrates in cytochrome P-450s. In
      the absence of L-arginine, NO readily oxidized the ferrous heme iron. The
      oxidation was prevented by the presence of bound L-arginine and enabled NOS to
      form a stable ferrous NO complex. Under oxygen-limited conditions, NO generated
      by neuronal NOS coordinated to its heme iron and formed a spectrally detectable
      ferrous-NO complex. Taken together, our results show that NO can bind to both
      ferric and ferrous NOS and may inhibit NO synthesis through its binding to the
      heme iron during catalysis.

PMID- 7524096
TI  - Localization and functional properties of a rat brain alpha 1A calcium channel
      reflect similarities to neuronal Q- and P-type channels.
AB  - Functional expression of the rat brain alpha 1A Ca channel was obtained by
      nuclear injection of an expression plasmid into Xenopus oocytes. The alpha 1A Ca
      current activated quickly, inactivated slowly, and showed a voltage dependence
      typical of high voltage-activated Ca channels. The alpha 1A current was partially
      blocked (approximately 23%) by omega-agatoxin IVA (200 nM) and substantially
      blocked by omega-conotoxin MVIIC (5 microM blocked approximately 70%). Bay K 8644
      (10 microM) or omega-conotoxin GVIA (1 microM) had no significant effect on the
      alpha 1A current. Coexpression with rat brain Ca channel beta subunits increased
      the alpha 1A whole-cell current and shifted the current-voltage relation to more
      negative values. While the beta 1b and beta 3 subunits caused a significant
      acceleration of the alpha 1A inactivation kinetics, the beta 2a subunit
      dramatically slowed the inactivation of the alpha 1A current to that seen
      typically for P-type Ca currents. In situ localization with antisense
      deoxyoligonucleotide and RNA probes showed that alpha 1A was widely distributed
      throughout the rat central nervous system, with moderate to high levels in the
      olfactory bulb, in the cerebral cortex, and in the CA fields and dentate gyrus of
      the hippocampus. In the cerebellum, prominent alpha 1A expression was detected in
      Purkinje cells with some labeling also in granule cells. Overall, the results
      show that alpha 1A channels are widely expressed and share some properties with
      both Q- and P-type channels.

PMID- 7524097
TI  - ard-1: a human gene that reverses the effects of temperature-sensitive and
      deletion mutations in the Escherichia coli rne gene and encodes an activity
      producing RNase E-like cleavages.
AB  - The Escherichia coli rne gene affects a variety of bacterial functions, including
      the activity of RNase E. We report the existence of a human gene (ard-1, for
      activator of RNA decay) that complements temperature-sensitive and deletion
      mutations of rne in E. coli, allowing growth of rne-defective cells, correcting
      abnormal cell shape, activating chemical decay of bulk mRNA, and producing site
      specific cleavages characteristic of RNase E in vivo and in vitro. ard-1 encodes
      a highly basic 13.3-kDa proline-rich peptide that has features in common with Rne
      and also with eukaryotic proteins implicated in RNA binding and macromolecular
      transport.

PMID- 7524099
TI  - A transcribing RNA polymerase molecule survives DNA replication without aborting
      its growing RNA chain.
AB  - We have demonstrated elsewhere that a precisely placed, stalled Escherichia coli
      RNA polymerase ternary transcription complex (polymerase-RNA-DNA) stays on the
      DNA template after passage of a DNA replication fork. Moreover, the bypassed
      complex remains competent to resume elongation of its bound RNA chain. But the
      simplicity of our experimental system left several important questions
      unresolved: in particular, might the observation be relevant only to the
      particular ternary complex that we studied, and can the finding be generalized to
      a transcribing instead of a stalled RNA polymerase? To address these issues, we
      have created three additional ternary transcription complexes and examined their
      fates after passage of a replication fork. In addition, we have examined the fate
      of moving RNA polymerase molecules during DNA replication. The results suggest
      that our previous finding applies to all transcription intermediates of the E.
      coli RNA polymerase.

PMID- 7524098
TI  - Bruton tyrosine kinase is tyrosine phosphorylated and activated in pre-B
      lymphocytes and receptor-ligated B cells.
AB  - The gene encoding Bruton tyrosine kinase (Btk) is known to be mutated in human X
      chromosome-linked agammaglobulinemia and in the Xid mouse. This kinase was
      examined in B lymphocytes before and after antigen receptor ligation and also in
      pre-B cells. Btk was found to be catalytically activated and tyrosine
      phosphorylated in response to anti-IgM stimulation in B cells. This kinase is
      also constitutively phosphorylated on tyrosine residues in pre-B cells. These
      findings point to a functional role for Btk in pre-antigen and antigen receptor
      signaling during B-cell development and provide a biochemical explanation for the
      X-linked genetic syndromes already linked to this kinase.

PMID- 7524100
TI  - Structural and functional alterations of a colicin-resistant mutant of OmpF porin
      from Escherichia coli.
AB  - A strain of Escherichia coli, selected on the basis of its resistance to colicin
      N, reveals distinct structural and functional alterations in unspecific OmpF
      porin. A single mutation [Gly-119-->Asp (G119D)] was identified in the internal
      loop L3 that contributes critically to the formation of the construction inside
      the lumen of the pore. X-ray structure analysis to a resolution of 3.0 A reveals
      a locally altered peptide backbone, with the side chain of residue Asp-119
      protruding into the channel, causing the area of the constriction (7 x 11 A in
      the wild type) to be subdivided into two intercommunicating subcompartments of 3
      4 A in diameter. The functional consequences of this structural modification
      consist of a reduction of the channel conductance by about one-third, of altered
      ion selectivity and voltage gating, and of a decrease of permeation rates of
      various sugars by factors of 2-12. The structural modification of the mutant
      protein affects neither the beta-barrel structure nor those regions of the
      molecule that are exposed at the cell surface. Considering the colicin resistance
      of the mutant, it is inferred that in vivo, colicin N traverses the outer
      membrane through the porin channel or that the dynamics of the exposed loops are
      affected in the mutant such that these may impede the binding of the toxin.

PMID- 7524101
TI  - Identification of the complement iC3b binding site in the beta 2 integrin CR3
      (CD11b/CD18).
AB  - The divalent cation-dependent interaction of the beta 2 integrin CR3 (CD11b/CD18)
      with the major complement opsonic C3 fragment iC3b is an important component of
      the central role of CR3 in inflammation and immune clearance. In this
      investigation we have identified the iC3b binding site in CR3. A recombinant
      fragment representing the CR3 A-domain, a 200-amino acid region in the ectodomain
      of the CD11b subunit, bound to iC3b directly and in a divalent cation-dependent
      manner. The iC3b binding site was further localized to a short linear peptide
      that also bound iC3b directly and inhibited iC3b binding to the A-domain as well
      as to CR3 expressed by human neutrophils. These data establish a major
      recognition function for the integrin A-domain and have important implications
      for development of novel antiinflammatory therapeutics.

PMID- 7524103
TI  - Host defense mechanisms against murine cytomegalovirus infection induced by poly
      I:C in severe combined immune deficient (SCID) mice.
AB  - The role of host defense mechanism against murine cytomegalovirus (MCMV)
      infection in mice with severe combined immunodeficiency (SCID) was investigated
      using polyinosinic:polycytidylic acid (poly I:C) as a nonspecific stimulator of
      the immune system. When administered ip at doses of 3.7 or 15 mg/kg 18 hr prior
      to infection of SCID mice with 10(3) or 10(4) plaque-forming units of MCMV, poly
      I:C significantly increased the animals' life span. Poly I:C enhanced, in a dose
      dependent manner (0.01-1 mg/kg), the peritoneal natural killer (NK)-cell activity
      and macrophage activity of SCID mice. When SCID mice were pretreated with anti
      asialo GM1 antibody (against NK cells) or anti-Mac1 antibody (against
      macrophages), poly I:C failed to stimulate the activity of NK cells and
      macrophages. Intraperitoneal administration of poly I:C also induced both early
      (2 hr) and late (18 hr) type interferon (IFN) in the peritoneal fluid and blood.
      The IFN-inducing activity of polyl:C was not affected by pretreatment of the mice
      with anti-asialo GM1 or anti-Mac1 antibody. Poly I:C also caused a significant
      but less pronounced increase in the life span of MCMV-infected SCID mice in which
      the NK cells or macrophages had been depleted by treatment with anti-asialo GM1
      or anti-Mac1 antibody, respectively. These results suggest that poly I:C-induced
      interferon as well as activation of NK cell and macrophages contribute to the
      host defense mechanism against MCMV infection in SCID mice.

PMID- 7524102
TI  - Role of the 75-kDa tumor necrosis factor receptor: inhibition of early
      hematopoiesis.
AB  - Biological effects of tumor necrosis factor alpha (TNF-alpha) are mediated
      through two cell surface receptors, the 55-kDa TNF receptor and the 75-kDa TNF
      receptor. The present study investigated the relative roles of the two TNF
      receptors in normal hematopoiesis. Using agonists (antibodies) specific for the
      55- and 75-kDa TNF receptors, we demonstrate differential roles of the two TNF
      receptors in hematopoiesis in that only the 55-kDa TNF receptor mediates
      antiproliferative effects of TNF-alpha on mature Lin- hematopoietic progenitor
      cells responding to granulocyte colony-stimulating factor or interleukin 3 alone.
      In contrast, the 75-kDa TNF receptor is essential in mediating inhibition of
      primitive Lin-Sca-1+ high-proliferative-potential colony-forming cells and
      inhibition of the total number of proliferative clones of individually cultured
      Lin-Sca-1+Rh123lo and Lin-Sca-1+Rh123hi cells.

PMID- 7524104
TI  - Histamine release and calcium concentrations in rat mast cells are dependent on
      intracellular ATP: effects of prostaglandin D2.
AB  - When PGD2 (10 microM), was added to rat mast cells, it caused a rapid increase in
      adenosine 3',5'-cyclic monophosphate (cyclic AMP) and decrease in adenosine 5'
      triphosphate (ATP), both of which recovered to their original levels within 2
      min. The accumulation of cyclic AMP was maximal at 30 s after challenge with
      PGD2. The minimum level of ATP was observed at 30 s after addition of PGD2. The
      initial rise in [Ca2+]i and the histamine release induced by anti-IgE (200
      micrograms/ml) were strongly inhibited at 30 s after incubation of the mast cells
      with PGD2. Removal of glucose from Tyrode-Hepes solution caused a rapid decrease
      on ATP level in mast cells, and showed strong inhibition on the rise in [Ca2+]i
      and histamine release induced by anti-IgE. Addition of glucose to the mast cells
      induced a time-dependent increase in ATP, and the rises in [Ca2+]i and histamine
      release were closely correlated with the recovery of ATP. These results suggested
      that the inhibitory mechanism of PGD2 on the initial rise in [Ca2+]i and
      histamine release induced by anti-IgE was due to the inhibition of ATP-dependent
      CA(2+)-release from the intracellular Ca(2+)-stores.

PMID- 7524105
TI  - Altered monamine metabolism in caudate-putamen of iron-deficient rats.
AB  - The effect of iron deficiency on brain monoamine metabolism using in vivo
      microdialysis techniques has not been previously reported. We, therefore,
      examined the monoamines, dopamine and norepinephrine, and their metabolites at
      steady state by in vivo microdialysis in rat brain caudate-putamen in 11-week-old
      iron-deficient anemic (hemoglobin < 7 g/dl) and control rats (Hb > 14 g/dl).
      Caudate-putamen dopamine (DA), dihydroxyphenyl acetic acid (DOPAC), and
      homovanillic acid (HVA) concentrations were increased by 53%, 57%, and 30% (p <
      0.001), respectively, in iron-deficient rats in samples collected over a 4-h
      period. While diminished numbers of D2 receptors have been previously reported,
      the present findings suggest an additional defect in monoamine uptake and
      catabolism.

PMID- 7524108
TI  - New considerations about the structure of the membrane of the living animal cell.
AB  - The philosophy and assumptions behind the research are summarized. The cell
      membrane in life is likely to be solid, of unknown thickness and of uncertain
      biochemistry; the myelin lamellae are artifacts and can not be regarded as sheafs
      of cell membranes. It is very unlikely that the cell membrane is covered with
      anatomically distinct receptors or channels. The physiological and biochemical
      properties attributed to them as structures are quite independent of their
      anatomy. The ionic channels originally proposed as a result of studies of
      excitable membranes have now been detected in virtually all membranes in the
      cell, including endoplasmic reticulum, liposomes and vacuoles. Physiologists
      believe that channels only open during excitation of nerve and muscle cells,
      which implies that they are permanently closed in non-excitable cells, although
      it has been known for more than 50 years that small ions cross the membranes
      continuously. Explanations are given for the appearance of artifacts.

PMID- 7524106
TI  - Involvement of nitric oxide in nitrous oxide anxiolysis in the elevated plus
      maze.
AB  - We recently reported that inhibition of nitric oxide (NO) production by the NO
      synthase (NOS) inhibitor L-NG-nitro arginine (L-NOARG) antagonized the behavioral
      effects of a benzodiazepine (BZ) in a mouse paradigm for screening anxiolytic
      drug activity. Because other research has found that the anesthetic gas nitrous
      oxide (N2O) also produces BZ-like behavioral effects, the present research was
      conducted to ascertain whether NO might also be involved in N2O anxiolysis. Male
      Swiss-Webster mice were tested in an elevated plus-maze inside an inflatable
      glovebag. Exposure to N2O significantly increased exploratory activity on the
      open arms of the plus-maze, as measured by the number of entries into the open
      arms and the time spent on the open arms. Pretreatment with L-NOARG significantly
      reduced the N2O-induced elevation in open arm activity. This antagonism of the
      N2O effect was reversed by ICV treatment of L-NOARG-pretreated mice with L
      arginine but not D-arginine. These findings indicate that NO possibly mediates
      behavioral effects of N2O in an animal model for anxiety.

PMID- 7524107
TI  - Intrathecal excitatory amino acid (EAA) agonists increase tail flick latencies
      (TFLs) of spinal rats.
AB  - The facilitation of spinal nociceptive reflexes that occurs after spinal
      transection reveals the existence of descending, supraspinally mediated
      inhibition. Substantial evidence indicates that the excitatory amino acids (EAAs)
      are involved in these spinal circuits. Therefore, it was hypothesized that reflex
      facilitation in the spinal animal might be due to the removal of inhibitory input
      normally exerted on the spinal action of EAAs. If so, the facilitatory decrease
      in reflex latency, observed in the spinal preparation, might be potentiated by
      intrathecal (IT) administration of EAA agonists. This was tested by comparing the
      effect of IT injections of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy
      5-methyl-4-isoxazole-propionic acid (AMPA) on the thermally elicited tail flick
      (TF) response of Intact and acute spinal rats. In intact rats, a low (0.25 nM)
      dose of NMDA produced a hyperalgesic decrease in latency, relative to saline,
      whereas higher doses produced an overall increase in latency. A large dose (0.5
      microM) produced overt signs of toxicity (crippling, self-mutilation, and loss of
      the reflex). Only the highest (1.0 nM) dose of AMPA affected the response,
      resulting in a significant increase. After spinal transection, the hyperalgesic
      reaction to 0.25 nM of NMDA was absent, and latencies were significantly
      increased by 1.0 nM. The toxic reaction to 0.5 microM appeared to be potentiated.
      Tail flick responses to AMPA were also significantly increased in spinal rats.
      Contrary to the prediction, reflex latencies were significantly increased by
      these drugs after spinal transection. It was suggested that, although the spinal
      action of EAAs appears to be supraspinally modulated, this influence may be
      facilitatory rather than inhibitory.

PMID- 7524109
TI  - Effects of fibroblast growth factors and related peptides on food intake by rats.
AB  - The effects of acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and
      related peptides, such as aFGF fragments, on food and water intake were
      investigated. Infusion of aFGF and bFGF into the third cerebral ventricle
      significantly suppressed food intake. The potency of aFGF was 1.5 that of bFGF in
      food intake inhibition. Both FGFs also suppressed water intake. Infusion of a
      carboxyl-terminal fragment of aFGF, aFGF-(114-140), did not affect food intake,
      whereas an amino-terminal fragment of aFGF, aFGF-(1-15), was significantly
      inhibitory. Other amino-terminal fragments, aFGF-(1-20) and aFGF-(1-29), did not
      affect food intake. However, [Ala16]aFGF-(1-29), in which the cysteine residue at
      position 16 was replaced with alanine, significantly suppressed food intake.
      Infusions of functional antagonists for FGFs, anti-aFGF, anti-bFGF, and anti-aFGF
      (1-15) IgGs, into the lateral hypothalamus significantly increased food intake.
      The results suggest that: aFGF, bFGF, and some amino-terminal peptides of aFGF
      participate in the central regulation of food intake; the lateral hypothalamus is
      involved in their feeding suppression actions; and these peptides may function as
      physiologically relevant substances in the adult central nervous system, other
      than as neurotrophic factors.

PMID- 7524110
TI  - Lessons from genetic knockout mice deficient in neural recognition molecules.

PMID- 7524111
TI  - Nucleic acid transfer through cell membranes: towards the underlying mechanisms.
AB  - Various cases of DNA (RNA) transfer through membranes of living cells are
      reviewed. They are classified into two major categories: those which occur in
      Nature (natural transfer) and those imposed by various physical and chemical
      treatments of cells (induced transfer). Among the examples of natural transfer
      surveyed are the transfer during bacterial conjugation, genetic transformation,
      viral infection of bacteria, and nuclear membrane trafficking. Consideration of
      the induced transfer is focused on the two methods most widely used at present to
      introduce foreign genetic information into pro- and eukaryotic cells: Ca2+ (and
      some other divalent cations)-induced and calcium phosphate-induced transfer, and
      transfer during electroporation of cells. Emphasis is made on the underlying
      mechanisms of transfer, or rather on what is currently known about them.
      Energetic aspects of transfer are also discussed and different tentative models
      of transfer are presented.

PMID- 7524112
TI  - Somatostatin binding sites in functional systems of the brain.

PMID- 7524113
TI  - Circadian variations in plasma monoamine metabolites level in alcoholic patients:
      a possible predictor of alcohol withdrawal delirium.
AB  - 1. Alcohol withdrawal symptoms in 17 alcoholics were classified into two groups
      according to the severity of their symptoms, and circadian variations in their
      plasma 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) levels
      during the alcohol withdrawal and the abstention periods were compared with those
      in normal controls by two-way ANOVA. 2. Circadian variations in plasma 5HIAA
      level in alcoholic patients manifested severe alcohol withdrawal symptoms and
      exhibited phase advances in both the withdrawal and the abstention periods and
      significantly higher levels in the abstention period. 3. Circadian variation in
      plasma HVA in the abstention period in alcoholics showed severe withdrawal
      symptoms demonstrating significantly higher levels compared with normal controls.
      4. These findings suggest that the serotonergic and dopaminergic activity may
      vary depending on the severity of alcohol withdrawal symptoms and the measurement
      of circadian variations in plasma 5HIAA and HVA levels could possibly be used as
      a predictor of hardly predictable alcohol withdrawal delirium.

PMID- 7524114
TI  - [Flow cytometer].

PMID- 7524116
TI  - Extraction and quantitation of neuropeptides in bone by radioimmunoassay.
AB  - The feasibility of extracting and quantifying neuropeptides in bone by
      radioimmunoassay was investigated in a study including 60 diaphyseal rat femora.
      Substance P, calcitonin gene-related peptide, neuropeptide Y and vasoactive
      intestinal polypeptide, previously identified in bone by immunohistochemistry,
      were extracted from separate homogenates of bone, periosteum and bone marrow in a
      solution of 4% EDTA and 2 M acetic acid. Measurable amounts of all four
      neuropeptides in bone, periosteum and bone marrow were obtained by
      radioimmunoassay in a reproducible manner. The neuropeptide immunoreactivities
      were characterized by reverse-phase high performance liquid chromatography. Among
      the four neuropeptides analyzed, neuropeptide Y consistently exhibited the
      highest concentrations in the different tissues. Overall, cortical bone showed
      the lowest neuropeptide concentrations. The concentration of vasoactive
      intestinal polypeptide was higher in periosteum than in bone marrow, whereas that
      of calcitonin gene-related peptide was uniform in these tissues. The
      distributional differences observed in bone tissue may be explained by a variety
      of physiological roles attributed to neuropeptides such as regulation of
      nociception, vasoactivity, immune function and local bone metabolism. The
      described methodology offers a new means of investigating a neuropeptidergic
      involvement in various disorders of the skeleton.

PMID- 7524115
TI  - [Electron microscope].

PMID- 7524119
TI  - Parenting stress and depression in children with mental retardation and
      developmental disabilities.
AB  - Although many types of behavioral and emotional disorders are prevalent in
      children with developmental delays, the phenomenology of childhood depression in
      this population remains poorly understood. This study examined the relationships
      among symptoms of depression, child problem behaviors, and parenting stress in a
      sample of 29 children with developmental delays. Results supported the usefulness
      of the Children's Depression Inventory (CDI) in assessing depression in these
      children initially reported by Matson, Barrett, and Helsel (1988). Parent ratings
      from the CDI were significantly associated with maternal depression, an index of
      DSM-III-R depression criteria, and negative self-image, anxiety, and conduct
      problems in children. A matched subsample of children (n = 12) with high versus
      low depression ratings revealed significant differences in total scores from the
      Parenting Stress Index (Abidin, 1986) and the index of DSM-III-R depression
      criteria. Together, these data suggest that children with developmental delays
      exhibit a similar pattern of symptoms and associated characteristics to those
      found in normal children with diagnoses of depression.

PMID- 7524118
TI  - A thiorphan-sensitive mechanism regulates the action of both exogenous and
      endogenous calcitonin gene-related peptide (CGRP) in the guinea-pig ureter.
AB  - The aim of this study was to assess the existence of mechanisms regulating the
      intensity and duration of action of calcitonin gene-related peptide (CGRP), the
      main candidate inhibitory transmitter released from capsaicin-sensitive afferents
      in the guinea-pig ureter. In a first series of experiments, performed in
      capsaicin-pretreated ureters, exogenously administered human alpha CGRP (h alpha
      CGRP) produced inhibition of contractions of the guinea-pig isolated ureter
      evoked by direct electrical stimulation of smooth muscle. The intensity and
      duration of the inhibitory effect of h alpha CGRP were potentiated by the
      inhibitor of neutral endopeptidase, thiorphan, while captopril and bestatin were
      without effect. In a second series of experiments, background motility of the
      guinea-pig ureter was evoked by administration of endothelin-1 (ET-1): electrical
      stimulation of intramural nerves produced a transient suppression of the ET-1
      evoked contractions, ascribable to release of endogenous CGRP. Thiorphan enhanced
      the inhibitory effect produced by endogenous CGRP, while bestatin and captopril
      were without effect. These findings demonstrate that a thiorphan-sensitive
      mechanism, presumably neutral endopeptidase, regulates the intensity and duration
      of the inhibitory activity of both exogenous and endogenous CGRP in the guinea
      pig ureter. The existence of a mechanisms for inactivation of the released
      peptide is consistent with the proposed role of CGRP as inhibitory
      neurotransmitter in this preparation.

PMID- 7524117
TI  - Peptide-evoked release of amylase from isolated acini of the rat parotid gland.
AB  - Investigations of the effects of the neuropeptides, substance P (SP), neurokinin
      A (NKA), neuropeptide K (NPK), gastrin releasing peptide (GRP), calcitonin gene
      related peptide (CGRP) and vasoactive intestinal peptide (VIP), and of
      acetylcholine on amylase secretion have been carried out on isolated acini of the
      rat parotid gland. Furthermore, the occurrence and location of the peptides in
      the gland was studied. Finally, binding of 125I-BH-SP to isolated acini were
      studied in order to characterize their tachykinin receptor(s) and their binding
      kinetics. Only SP, NKA, NPK and VIP stimulated amylase release. VIP, however,
      with a rather low potency (EC50 at 155 nmol/l). Simultaneous stimulation with two
      compounds elicited additive responses, except for VIP and acetylcholine which
      elicited an effect significantly above additive response. Only SP, NKA, VIP and
      CGRP could be identified in extracts of the gland. The immunoreactivity of these
      peptides could be located to varicose nerve fibers in the gland. Binding of
      labeled SP to the isolated acini exhibited the characteristics of a genuine
      agonist/receptor interaction, and the rank order of displacement potencies
      indicated the presence of NK1-receptors. Thus, the results of the present study
      support previous suggestions that the tachykinins and VIP are likely to be
      involved in amylase secretion in the rat parotid gland.

PMID- 7524120
TI  - Bradykinin induces generation of reactive oxygen species in bovine aortic
      endothelial cells.
AB  - We investigated the effects of bradykinin on intracellular oxidative stress in
      bovine aortic endothelial cells using a hydroperoxide-sensitive fluorescent dye,
      2',7'-dichlorofluorescein (DCFH), and a laser scanning confocal microscope.
      Bradykinin induced an immediate increase in intracellular Ca2+ concentration, and
      stimulated the oxidation of DCFH in cultured endothelial cells. This bradykinin
      induced oxidation of DCFH was inhibited by pretreatment with N-(2
      mercaptopropionyl)-glycine (MPG) and 1,3-dimethyl-thiourea (DMTU), scavengers of
      hydroxyl radical, and the removal of extracellular Ca2+ but was unaffected by NG
      nitro-L-arginine or NG-monomethyl-L-arginine, both inhibitors of nitric oxide
      (NO) synthase. On the other hand, pretreatment with indomethacin and aspirin,
      inhibitors of cyclooxygenase, inhibited bradykinin-induced oxidation of DCFH.
      These findings suggest that bradykinin increases intracellular Ca2+ and
      stimulates the generation of hydroxyl radical-like reactive oxygen species
      (scavenged by MPG or DMTU) via the cyclooxygenase pathway but not via the
      reaction of NO and superoxide anion.

PMID- 7524121
TI  - Nitric oxide-related inhibition of carotid chemosensory nerve activity in the
      cat.
AB  - The hypothesis that endogenous nitric oxide may play a physiological role in the
      regulation of carotid chemosensory activity was tested in this study. The nitric
      oxide synthase (NOS) inhibitors, L-nitro-arginine-methyl ester (L-NAME, 25-200
      microM) and NG-monomethyl-L-arginine acetate (L-NMMA, 50 and 100 microM) were
      used to study its effects on the chemosensory activity of perfused and superfused
      cat carotid bodies (n = 21) in vitro at 37-37 degrees C. L-NAME elicited slow
      excitation of the sensory activity as did L-NMMA. The peak-response was dose
      dependent, and approached saturation around 200 microM. The excitation by L-NAME
      showed the following characteristics (mean +/- SEM): latency of response, 2.2 min
      +/- 0.3 min; time to peak response, 5.5 min +/- 1.0 min and the peak response
      increased to 407 +/- 42 imp/sec from 88 +/- 13 imp/sec. The peak response was
      significantly different (P < 0.05) from the baseline activity. L-arginine (50-500
      microM) only briefly reversed the stimulation. Hypoxia enhanced the excitation by
      L-NAME. On the other hand, sodium nitroprusside (SNP, 0.5-10 microM) which
      supplies NO, terminated the excitatory effect of L-NAME. The results provide
      evidence in favor of an inhibitory role of endogenous NO in the carotid body, and
      exogenous application of NO confirms the inhibitory effect.

PMID- 7524122
TI  - [Physiopathology of pruritus].
AB  - Itching is the predominant symptom of inflammatory skin diseases. Present
      evidence indicates that histamine and unidentified peptides mediate itching. No
      evidence is available that lymphokines or cytokines play a direct role as itch
      mediators. Prostaglandins serve an important synergistic function in itching.
      Evidence points to a role for opioid peptides of the central nervous system in
      the perception of itch and as direct mediators. Pruritus may be a prominent
      symptom in uraemia, biliary obstruction, atopic dermatitis and neoplasia.

PMID- 7524123
TI  - [Current aspects of hepatitis C].

PMID- 7524124
TI  - [Current developments in the diagnosis of hepatitis C].
AB  - Since the discovery of hepatitis C virus five years ago eight complete isolates
      and a large number of partial isolates have been sequenced. By comparing
      sequences, six HCV types can be differentiated which show more than 35%
      divergency in the NS5 proteins. The course of hepatitis C and the response rate
      after interferon therapy may be dependent on the HCV type. Serological tests for
      the diagnosis of acute and chronic hepatitis C have been improved, so that more
      than 90% of patients seroconvert at the peak of transaminases during acute
      infection; however in single cases, seroconversion can last up to nine months
      after onset of disease. Antibodies which can be detected in the acute and chronic
      phase of hepatitis C are directed against structural and nonstructural proteins.
      Most recently, also antibodies enveloping proteins E1 and E2 have been
      identified. These antibodies obviously do not seem to neutralize the virus. In
      patients with acute hepatitis C and complete recovery antibodies may persist up
      to ten years after onset of disease. At present there is no marker for past
      infection or immunity to HCV. Chronicity of hepatitis C and infectivity of
      patients can only be shown by detection of viral RNA using RT-PCR. Indications to
      perform PCR are patients prior to and after interferon therapy, hemodialysis
      patients, patients undergoing immunosuppression, new-born babies of mothers with
      chronic hepatitis C and patients with acute hepatitis C who are negative for
      antibodies.

PMID- 7524125
TI  - [Sodium valproate--current status of pharmacological research].
AB  - Valproic acid has a wider antiepileptic spectrum than any other antiepileptic
      drug (AED) in clinical use. Valproate administration causes many neurochemical
      and neurophysiological alterations, including increased GABA levels, modified
      GABA turnover and release, decreased gamma-hydroxybutyrate synthesis and release,
      increased serotonin and dopamine release, decreased aspartate levels, reduction
      of repetitive firing of neurons, and possibly a reduction in calcium (T)
      currents; however, none of these effects have consistently and unequivocally been
      linked to the antiepileptic action of valproate.

PMID- 7524126
TI  - [Therapeutic endoscopy and pancreatic pathology].

PMID- 7524127
TI  - [Oncological management of patients with metastatic breast cancer].

PMID- 7524128
TI  - Acute phase response in rheumatoid arthritis patients treated with low doses of
      cyclosporin A.

PMID- 7524129
TI  - From tissue polypeptide antigen to specific cytokeratin assays.

PMID- 7524131
TI  - FDA approved new drug bulletin: aprotinin injection (trasylol), tacrolimus
      (prograf).

PMID- 7524130
TI  - Monoclonal antibody M3 used in tissue polypeptide-specific antigen assay for the
      quantification of tissue polypeptide antigen recognizes keratin 18.
AB  - Recently, a new 'specific tissue polypeptide antigen (TPA)' test was introduced
      and designated tissue polypeptide-specific antigen (TPS); it is based on the
      monoclonal antibody (MAb) anti-TPS, M3. We have tested the specificity of this
      antibody by immunocyto- and immunohistochemistry, gel electrophoresis and
      immunoblotting. MAb M3 bound to intermediate filaments of epithelial cells and
      revealed a staining pattern identical to cytokeratin (CK) 18-specific MAb (DE
      K18) on tissue sections of various human tissues. On immunoblots of proteins
      extracted from various epithelial cell lines, M3 reacted with a 45-kD protein
      corresponding to CK18, and on immunoblots of proteins isolated from MCF-7 culture
      fluid M3 stained three bands, 45, 33 and 29 kD. The same bands were stained with
      CK18-specific MAb, indicating that they represent CK18 and its degradation
      products. TPA, used as a tumor marker in clinical diagnoses and follow-up, was
      shown to be a degradation product of CK 8, 18 and 19. In contrast to TPA, MAb M3
      did not stain CK8 and CK19 present on immunoblots.

PMID- 7524132
TI  - [Substance P and rheumatic diseases].
AB  - Substance pertains to a group of linear molecules of 10-30 amino-acid residues
      produced by nervous fibers and called neuropeptides. It is a mediator of pain
      transmission, and modulates or stimulates the activity of several cell types,
      i.e. lymphocytes and mast cells. The concept of neurogenic inflammation is based
      on the release of substance P and related peptides by an axon eflex mechanism. In
      rheumatic diseases, substance P may enhance inflammatory joint reactions. In
      rheumatoid arthritis, high SP levels were demonstrated in synovial fluid by our
      group and others. Results in fibromyalgia are contradictory. Algoneurodystrophia
      may be modulated by substance P release. Topical use or capsaicin and development
      of peripheral inhibitory drugs offer novel treatments based on this concept.

PMID- 7524134
TI  - [Role of radiotherapy in the treatment of cancer].
AB  - In France, 120,000 patients are irradiated every year as a part of cancer
      treatment. Radiotherapy can be delivered with a palliative goal, to decrease pain
      due to bone metastases, to treat spinal cord or cerebral compression, to treat
      tumor bleeding or to decrease tumor volume in inoperable patients. Radiotherapy
      can be delivered alone in a curative intent, for small tumours or in patients
      with tumors inoperable for local reasons. Radiation therapy can also be
      associated to surgery, pre or post-operatively to facilitate surgery or to reduce
      the risk of local or regional recurrence. In association with chemotherapy,
      radiotherapy is employed to increase local control of aggressive tumors. The
      delivered dose, fractionation and duration of radiotherapy must be discussed for
      each case but high doses can only be delivered in relatively small volumes.

PMID- 7524133
TI  - [A new bacterium: Rochalimaea].
AB  - Originally limited to trench fever, infections due to Rochalimaea now comprise
      manifestations particular to patients with human immunodeficiency virus
      (bacillary angiomatosis and hepatic peliosis), but also manifestations as diverse
      as isolated fever, septicaemia, endocarditis, lymphocytic meningitis, or central
      neurological disorders, in immunodepressed or immunocompetent subjects. The
      involvement of Rochalimaea in cat-scratch fever remains debated. Microbiological
      analysis used for diagnosis has been modified to allow isolation of these new
      bacteria, whose culture is slow and difficult, in the course of the above-cited
      clinical manifestations, which should further extend the range of Rochalimaea
      infections.

PMID- 7524135
TI  - [Thyroid-stimulating hormone receptor and thyroid diseases].
AB  - Since the description of the structure of the TSH receptor using molecular
      biology techniques, it has become possible to analyse the role of anomalies of
      this receptor in thyroid disorders. Implicated in the pathophysiology of Graves'
      disease by indirect observations, the autoantigenic role of the TSH receptor has
      now been clearly confirmed. Nevertheless, the epitopes of the extracellular
      domain of the receptor corresponding to each type, stimulatory or epitopes of the
      extracellular domain of the receptor corresponding to each type, stimulatory or
      blocking, of anti-receptor toward activation or blocking. The events that induce
      and maintain autoimmunization to the receptor remain hypothetical, but the
      possible existence of soluble forms of the receptor opens new perspectives. In
      practice, however, assessment of TSH anti-receptor antibodies is useful in
      managing Graves' disease and in certain cases of primary myxoedema linked to the
      presence of blocking antibodies; it is mandatory in pregnant women for detection
      of foetal disease induced by maternal antibodies. The responsibility of the
      receptor is sought in other thyroid diseases such as toxic adenoma, rare forms of
      nonimmunologic, familial hyperthyroidism, simple goiter, nodules and lack of
      response to TSH. Recently, a mutation mapped into the 3rd intracellular loop has
      been shown in toxic adenoma. Such discoveries are as important for physicians
      (and patients) as for cellular biologists.

PMID- 7524136
TI  - Effect of cionin on histamine and acid secretion by the perfused rat stomach.
AB  - BACKGROUND: The protochordean octapeptide cionin is structurally a hybrid of
      mammalian cholecystokinin (CCK) and gastrin. An earlier study has shown that
      cionin in mammals stimulates gallbladder contraction and gastric somatostatin
      release, similarly to CCK-8. METHODS: In the present study we examined the effect
      of cionin on histamine release and acid secretion of the stomach, both effects
      being mediated by CCK-B/gastrin receptors. RESULTS: Cionin induced a
      concentration-dependent increase in histamine release and acid secretion in the
      isolated, vascularly perfused rat stomach, detectable at a concentration of 4 pM
      and reaching a maximum at a concentration of 512 pM. The CCK-B/gastrin receptor
      antagonist L 365,260 abolished the stimulating effect of cionin on both histamine
      release and acid secretion, whereas the CCK-A receptor antagonist L 364,718 only
      had a faint effect. CONCLUSION: Cionin is a potent and efficient stimulator of
      gastric histamine release and acid secretion interacting via a CCK-B receptor.

PMID- 7524138
TI  - Mycoplasma pneumoniae lacks immunologically-active eukaryotic actin-like
      antigens.
AB  - Mycoplasma pneumoniae was tested for immunologically active eukaryotic actin-like
      antigens with the use of both polyclonal and monoclonal anti-actin antibodies. No
      reactivity was demonstrable. Monoclonal antibody OC2F5, which reacts with a M.
      pneumoniae antigen that co-migrates with actin in one-dimensional sodium dodecyl
      sulphate polyacrylamide electrophoresis, did not recognize actin. Organism
      specific actin antigens are not likely to be responsible for the development of
      smooth muscle antibodies during acute M. pneumoniae infection.

PMID- 7524140
TI  - Symptoms and symptom scores in BPH.
AB  - Symptoms occupy a central role in the management of bladder outflow obstruction
      (BOO) due to benign prostatic hyperplasia (BPH). Patients present with symptoms
      and are concerned with their resolution. Many urologists use symptoms as the
      basis for the diagnosis of bladder outflow obstruction and for assessing the
      effects of treatment. In this review we will discuss the relationship between the
      'obstructive' symptoms of prostatism, and the objective evidence of disordered
      voiding and bladder outflow obstruction, and will highlight gaps in our
      understanding of the pathophysiology of the symptoms of prostatism.

PMID- 7524139
TI  - Malignant rhabdoid tumour of the kidney in an adult: a case report with
      immunohistochemical and ultrastructural investigation.
AB  - Rhabdoid tumours (RT) are highly aggressive neoplasms most often occurring in
      kidneys of children. Few cases of extrarenal RT have been reported among adults.
      This paper describes the first case of a RT in the kidney of an adult.

PMID- 7524137
TI  - Expression of CD43 epitopes on NK and T cells.
AB  - CD43 epitope expression was studied with a panel of monoclonal antibodies (MoAbs)
      by immunohistochemistry on freeze sections of lymphoid tissues. The MoAb WEN3
      stained most cells weakly in the T areas and scattered splenic red pulp cells
      strongly, whereas the other MoAbs strongly stained the majority of the cells in
      the T areas but gave variable staining patterns of cells in the non-T areas. Flow
      cytometry on CD4+ and CD8+ T cells (T4 and T8 cells), freshly isolated NK cells
      and LAK cells showed distinct staining profiles for each cell type, with epitope
      expression patterns of T8 cells lying between those of T4 cells and NK/LAK cells.
      T8 cells were split by one of the MoAbs, the NK cells, but not LAK cells, were
      split by two other MoAbs.

PMID- 7524142
TI  - Alpha-1 receptor mediated smooth muscle regulation in benign prostatic
      hyperplasia.
AB  - Symptoms in benign prostatic hyperplasia (BPH) are partially caused by an
      increased prostatic smooth muscle tone. This tone depends on extra- and
      intracellular Ca2+ stores and is regulated by various second messenger pathways.
      We investigated the role of intracellular Ca2+ stores and cyclic 3'-5' adenosine
      monophosphate (cAMP) in BPH. Contractions elicited by the specific alpha 1
      receptor agonist phenylephrine (PE) were inhibited by the selective alpha 1
      receptor antagonists prazosin and YM 617. To elucidate the contribution of
      intracellular Ca2+ stores to the alpha 1-receptor induced contraction nifedipine,
      a blocker of voltage dependent L-type Ca2+ channels (VDCC) was applied and found
      to inhibit the PE induced contractions up to 65%. To further confirm the
      participation of intracellular Ca2+ stores, we applied ryanodine (10 microM)
      which reduced the alpha 1-receptor mediated contractions up to 80%. The remaining
      contraction was sensitive to nifedipine. The cAMP pathway mediating smooth muscle
      relaxation by regulating intracellular Ca2+ concentrations ([Ca2+]i) was also
      investigated. Nonspecific phosphodiesterase (PDE) inhibitors such as papaverine
      (0.5 mM) and theophylline (1 mM) and the specific PDE inhibitor milrinone (0.5
      mM), all of which prevent degradation of cAMP, suppressed the PE induced
      contractions by 82%, 91% and 68%, respectively. Forskolin (50 microM), an
      activator of adenylylecyclase (AC), inhibited the PE induced contractions by 83%.
      The membrane permeable cAMP analog, N6-2'-0-dibutyryladenosine derivative
      (dBcAMP) also reduced the PE induced response by 70%.

PMID- 7524141
TI  - Alfuzosin in the treatment of benign prostatic hyperplasia: effects on symptom
      scores, urinary flow rates and residual volume. A multicentre, double-blind,
      placebo-controlled trial. ALFECH Study Group.
AB  - In order to assess the efficacy and safety of alfuzosin, a selective alpha-1
      receptor antagonist, 205 patients with Benign Prostatic Hyperplasia (BPH) were
      randomly assigned in a double-blind, placebo-controlled manner, to receive either
      alfuzosin 2.5 mg TID or placebo TID during 12 weeks. After 12 weeks symptom
      scores-assessed according to the Madsen-Iversen scale were significantly reduced
      in the alfuzosin group and peak flow rate significantly increased compared to the
      placebo group. There were no significant differences concerning adverse events or
      withdrawals. Alfuzosin proved to have a beneficial effect in patients with
      symptomatic BPH with few and minor adverse events.

PMID- 7524143
TI  - Prostatic enlargement, symptomatology and pressure/flow evaluation:
      interrelations in patients with symptomatic BPH.
AB  - INTRODUCTION: Benign prostatic hyperplasia (BPH) is the most common pathologic
      condition to afflict the aging male. Many patients with symptomatic BPH undergo
      prostatectomy without rigorous evaluation. Three concepts should be considered
      before any treatment of a patient with symptomatic BPH; Prostatic enlargement,
      symptomatology and bladder outflow obstruction. PATIENTS AND METHODS: The study
      comprised 188 consecutive patients with symptomatic BPH, all eligible after
      pressure/flow examination. One-hundred-seventy-four of the patients answered the
      DAN-PSS questionnaire, 140 of the patients had their prostate size measured by
      transrectal ultrasonography. One-hundred-fifty-three patients were able to
      perform a free flow measurement upon arrival. Uroflowmetry, symptomatology and
      prostate size were matched with the results of pressure/flow examination.
      RESULTS: Neither uroflowmetry, symptomatology nor prostate size correlated well
      with bladder outlet obstruction. The positive predictive value for infravesical
      obstruction was 88% if a maximum flow rate under 10 ml/s was used. Symptomatology
      could not be used to differentiate between patients with bladder outlet
      obstruction and patients without obstruction. The positive predictive value for
      infravesical obstruction was 76% if a prostate volume over 40 ml was chosen.
      DISCUSSION: The purpose of diagnostic evaluation in patients with BPH, is to
      identify precisely the pathophysiology underlying the patients condition, so that
      rational therapy can be selected. CONCLUSION: The disease entity of BPH is
      characterized by the interaction of prostate enlargement, the subjective symptom
      complex of prostatism, and urodynamic infravesical obstruction. Since it is
      impossible to interpolate from one to another of these conditions, a
      comprehensive evaluation of a patient with symptomatic BPH should include an
      assessment of all of these conditions.

PMID- 7524144
TI  - The intramural innervation of the human vas deferens and seminal vesicle in
      infants and children.
AB  - Immunohistochemical methods were used to study the autonomic innervation of the
      vas deferens and seminal vesicle in a series of human postnatal specimens ranging
      in age from 1 month to 3 years. The occurrence and distribution of nerves
      immunoreactive for the neuropeptides vasoactive intestinal polypeptide (VIP),
      neuropeptide Y (NPY) substance P (SP) and calcitonin gene-related peptide (CGRP)
      were investigated. In addition immunoreactivity to tyrosine hydroxylase (TH),
      dopamine-beta-hydroxylase (DBH) and to protein gene product (PGP 9.5), a general
      nerve marker were also studied. A neurohistochemical method was used to localise
      acetylcholinesterase. The results obtained from either organ were similar.
      Regardless of age, a rich plexus of nerve fibres immunoreactive for PGP 9.5 was
      present both within the muscle coat and also beneath the epithelium of the vas
      deferens and seminal vesicle. Some acetylcholinesterase containing nerves
      occurred in the muscle coat but the majority were found under the epithelium in
      the connective tissue of the mucosa. TH and DBH-containing nerves (presumably
      noradrenergic in type) formed dense intramuscular plexuses but none occurred
      subepithelially. In contrast NPY-containing nerves formed a less dense
      intramuscular plexus and were also observed beneath the epithelium. Thus while
      NPY may occur in some of the intramuscular noradrenergic nerve fibres it is
      clearly not confined to this type of nerve in either the vas deferens or the
      seminal vesicle. SP- and CGRP-containing nerves were extremely infrequent and,
      when observed, were confined to the muscle coat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524145
TI  - Long-term probability of prostatism vs general morbidity and mortality.
      Prospectively obtained data in a randomly selected cohort aged > 50 years.
AB  - In a 7-year study of 178 randomly selected healthy men older than 50, data were
      respectively obtained concerning treatment for benign prostatic hypertrophy (BPH)
      and overall morbidity and mortality. Plain symptom scores were calculated in all
      cases and urinary voiding was recorded in 112. The maximum flow rate was read and
      the pattern of flow curve determined. Log rank test and survival curves were used
      in evaluation of results. The general risk of death or disease overshadowing BPH
      greatly exceeded the probability of surgery for prostatism. The only factor
      predicting need for prostatectomy was a symptom score higher than 6 points. If
      the symptom score is low and indications for treatment are otherwise, relative,
      an expectant attitude to surgery for BPH is advocated.

PMID- 7524146
TI  - [Diffuse thymus hyperplasia following chemotherapy for nodular sclerosing Hodgkin
      lymphoma].
AB  - A persistent or new mass in the anterior mediastinum after chemotherapy for
      mediastinal lymphoma poses a major differential diagnostic problem.
      Misinterpretation as a persistent or recurrent tumor may lead to additional
      unnecessary and potentially harmful therapy. Benign mediastinal tumors, albeit
      very rare, need confirmation by biopsy since they cannot be distinguished by
      radiological methods from persistence or relapse of lymphoma. We present a case
      report of a patient with diffuse thymic hyperplasia following successful
      chemotherapy for nodular sclerosing Hodgkin's disease, with a review of the
      literature.

PMID- 7524147
TI  - The origin of life on the earth.
AB  - Growing evidence supports the idea that the emergence of catalytic RNA was a
      crucial early step. How that RNA came into being remains unknown.

PMID- 7524149
TI  - RNA editing: transfer of genetic information from gRNA to precursor mRNA in
      vitro.
AB  - RNA editing in the mitochondrion of Trypanosoma brucei extensively alters the
      adenosine triphosphate synthase (ATPase) subunit 6 precursor messenger RNA (pre
      mRNA) by addition of 447 uridines and removal of 28 uridines. In vivo, the guide
      RNA gA6[14] is thought to specify the deletion of two uridines from the editing
      site closest to the 3' end. In this study, an in vitro system was developed that
      accurately removed uridines from this editing site in synthetic ATPase 6 pre-mRNA
      when gA6[14] and ATP were added. Mutations in both the guide RNA and the pre-mRNA
      editing site suggest that base-pairing interactions control the number of
      uridines deleted in vitro. Thus, guide RNAs are required for RNA editing and for
      the transfer of genetic information to pre-mRNAs.

PMID- 7524148
TI  - Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis
      mouse model.
AB  - The effect of the number of cystic fibrosis (CF) alleles on cholera toxin (CT)
      induced intestinal secretion was examined in the CF mouse model. CF mice that
      expressed no CF transmembrane conductance regulator (CFTR) protein did not
      secrete fluid in response to CT. Heterozygotes expressed 50 percent of the normal
      amount of CFTR protein in the intestinal epithelium and secreted 50 percent of
      the normal fluid and chloride ion in intestinal epithelium and secreted 50
      percent of the normal fluid and chloride ion and fluid secretion suggests that CF
      heterozygotes might possess a selective advantage of resistance to cholera.

PMID- 7524151
TI  - Marker antibodies of rheumatoid arthritis: diagnostic and pathogenetic
      implications.
AB  - Rheumatoid arthritis (RA) is associated with several autoantibodies specific
      enough to serve as diagnostic and prognostic markers. These include rheumatoid
      factor (RF), antikeratin antibody (AKA), antiperinuclear factor (APF), and anti
      RA33. The first three, and possibly also anti-RA33, may precede the onset of
      clinical RA. The prevalence of positive test reactions depends on the period
      between taking the specimen and onset of disease; when the period is short, the
      prevalence is nearly the same as in established disease. Thus, RA has a long
      asymptomatic period with broadening immunological activity. The assays for AKA
      and APF (and possibly also for anti-RA33), compared with RF testing, yielded
      greater specificity rather than the ability to define any subgroup with
      particularly severe disease. Used together, the above marker antibodies may form
      a new and more enlightened basis for defining seropositive RA. It is commonly
      believed that genetically mediated immune response plays an important role in the
      initiation of RA. However, the role of the major histocompatibility complex
      antigens may be in modulation of the inflammatory reaction in a later phase.

PMID- 7524152
TI  - Early detection of prostate cancer: the nature of cancers detected with current
      diagnostic tests.
AB  - The goal of an early detection program is not to detect all prostate cancers, but
      only to detect those that are potentially morbid or lethal (clinically important
      cancers). The prevalence of such cancers in the population of 50-year-old men can
      be estimated to be about 6%, using both epidemiologic and pathologic data.
      Screening trials using PSA and/or TRUS instead of or in addition to DRE have
      approached this rate of detection. As Fig 1 illustrates, screening appears to
      detect almost all of the clinically important cancers in the study population.
      The fear that these tests will detect a high proportion of latent, or clinically
      unimportant, cancers appears to be unfounded. Our studies and those of others
      support the concept that 85% to 90% of cancers detectable with current tests are
      clinically important. The detection of nonpalpable cancers by PSA or TRUS reduces
      the proportion of cancers detected at an advanced stage without increasing
      significantly the detection of latent or clinically unimportant cancers. Despite
      this analysis, we still lack definitive data to show that screening and treating
      early stage cancers will decrease the mortality rate of this disease. Such a
      conclusion will require a long-term, randomized screening trial or a comparison
      of mortality rates among large populations of men differing primarily in the
      extent of screening for prostate cancer.

PMID- 7524150
TI  - Rescue of T cell-specific V(D)J recombination in SCID mice by DNA-damaging
      agents.
AB  - Assembly of antigen receptor V (variable), D (diversity), and J (joining) gene
      segments requires lymphocyte-specific genes and ubiquitous DNA repair activities.
      Severe combined immunodeficient (SCID) mice are defective in general double
      strand (ds) DNA break repair and V(D)J coding joint formation, resulting in
      arrested lymphocyte development. A single treatment of newborn SCID mice with DNA
      damaging agents restored functional, diverse, T cell receptor beta chain coding
      joints, as well as development and expansion of thymocytes expressing both CD4
      and CD8 coreceptors, but did not promote B cell development. Thymic lymphoma
      developed in all mice treated with DNA-damaging agents, suggesting an
      interrelation between V(D)J recombination, dsDNA break repair, and
      lymphomagenesis.

PMID- 7524153
TI  - Newer applications of serum prostate-specific antigen in the management of
      prostate cancer.
AB  - The information contained in this article indicates that PSA will have an
      increasing role in the management of prostate cancer. For example, it is now
      essential for optimal diagnosis if prostate cancer detection is the goal.
      Prospects are high that more information about PSA density relationships, PSA
      velocity phenomenologies, and possible PSA isoforms will increase diagnostic
      accuracy. It would also seem that PSA will improve staging accuracy not only by
      better manipulation of multiple preoperative parameters (eg, cancer grade,
      volume, PSA, etc) but possibly by the molecular detection of minute amounts of
      occult prostate cancer cells in bone, blood or lymph nodes, or by improved use of
      immune scanning. Finally, the use of these more sophisticated staging approaches
      together with increasingly sensitive PSA assays and possibly androgen provocative
      testing might allow the prospect that the potentially curative therapies can be
      almost immediately assessed for efficacy, thereby increasing prospects for
      therapeutic progress. Finally, PSA may become even more important for
      manipulating hormone therapies (eg, IAS therapy) or it could form a basis for new
      treatments such as immune or gene therapy.

PMID- 7524154
TI  - Evaluation of changes in PSA in the management of men with prostate cancer.

PMID- 7524155
TI  - The clinical and biological study of androgen independent prostate cancer (AI
      PCa).

PMID- 7524156
TI  - Assessment of quality of life in patients with prostate cancer.

PMID- 7524157
TI  - Prostate cancer: improving the therapeutic index.

PMID- 7524159
TI  - A phase I trial of 3-hour infusions of paclitaxel (Taxol) with or without
      granulocyte colony-stimulating factor.
AB  - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a novel
      antitubulin agent derived from the bark of the Pacific yew tree, may be one of
      the most active single agents in our chemotherapy armamentarium. Concern over
      acute hypersensitivity reactions has resulted in an administration schedule
      consisting of a 24-hour infusion. We conducted a phase I trial of a 3-hour
      infusion of paclitaxel to determine whether a 3-hour infusion could be
      administered with relative safety, and to identify the maximal tolerated dose
      with and without granulocyte colony-stimulating factor (G-CSF) support. Thirty
      five patients with advanced, untreatable malignancies received a 3-hour infusion
      of paclitaxel once every 3 weeks. Groups of three patients were entered at
      escalating dose levels in a traditional phase I design consisting of two parallel
      arms: arm A (without G-CSF) and arm B (with G-CSF). Dose levels of paclitaxel
      ranged from 210 mg/m2 to 300 mg/m2. Patients assigned to the G-CSF arm received 5
      micrograms/kg/d subcutaneously starting on day 2. All patients were pretreated
      with dexamethasone, diphenhydramine, and ranitidine, and were monitored
      continuously for cardiac arrhythmias during the first treatment. The dose
      limiting toxicity for paclitaxel without G-CSF was myelosuppression at the 250
      mg/m2 dose level and with G-CSF was peripheral neuropathy at the 300 mg/m2 dose
      level. The mean absolute neutrophil count at the 250 mg/m2 dose level when
      administered with and without G-CSF support was 4,500/microL and 840/microL,
      respectively. Neuropathy appeared to be dose related and somewhat cumulative. One
      patient who previously received cisplatin developed a severe grade III peripheral
      neuropathy at the 300 mg/m2 dose level, which left her unable to use her hands
      and wheelchair bound; the peripheral neuropathy slowly resolved to a grade I
      level. Twenty-seven of III courses (24%) were associated with grade III
      arthralgias or myalgias, requiring narcotics for pain control. Prednisone was
      empirically started in 10 patients and found to be helpful in the control of
      these symptoms. One of 35 (2.9%) patients had a grade III anaphylactic reaction.
      No clinically significant cardiac arrhythmias were observed. Two previously
      treated patients (one with breast cancer and one with ovarian cancer) had a
      partial response. The maximum tolerated dose of paclitaxel administered as a 3
      hour infusion was 210 mg/m2 without G-CSF and 250 mg/m2 with G-CSF.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7524160
TI  - Factor VIII inhibitors: structure and function in autoantibody and hemophilia A
      patients.

PMID- 7524161
TI  - Standardisation and adaptation of the Denver Developmental Screening Test (DDST)
      and Denver II for use in Singapore children.
AB  - OBJECTIVE: To modify and standardise the Denver Developmental Screening Test
      (DDST) and Denver II for developmental screening of children in Singapore.
      METHOD: The study used a quota sample of 2,194 Singapore children aged 4 weeks to
      6 years. Logistic regression analysis established the 25th, 50th, 75th, and 90th
      percentile passing age for achieving the test tasks. Subgroup differences in Sex,
      Ethnicity, Social Class and Mother's Education were analysed by stepwise logistic
      regression; the composite norms for items with statistically significant subgroup
      differences (p < or = 0.10), were then adjusted by weighting based on the
      composition of Singapore children. The study protocol was based on the DDST
      (1975) and Denver II (1990), the latest version of the DDST. Modifications were
      introduced to improve on the sensitivity of the test and to make the test more
      suited to Singapore culture. MAIN FINDINGS: Out of the 215 items studied, 115
      items were selected to form the new test, DDST, Singapore, DDST, Singapore shares
      63% of the items with DDST (1975) and 67% of the items with Denver II. Among the
      comparable items, differences between the norms of Singapore and Denver children
      greater than 10% were demonstrated in more than 30 items, and differences of
      greater than 20% in 10 items. Within the study sample of Singapore children,
      there were relatively smaller differences among the subgroups studied. Only 10
      items had clinically significant subgroup differences of more than 10%. None had
      more than 20% difference. CONCLUSION: DDST, Singapore is substantially different
      from the DDST (1975) and Denver II (1990). The use of the local standardised
      version for developmental screening of Singapore children is justified.

PMID- 7524158
TI  - A phase II trial of paclitaxel (Taxol) in advanced esophageal cancer: preliminary
      report.
AB  - A cooperative, phase II single-arm trial was conducted at two large tertiary
      referral cancer centers to evaluate the antineoplastic activity and toxicities of
      paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment
      of patients with advanced esophageal cancer. The drug was given at a dose of 250
      mg/m2 as a 24-hour continuous infusion. Repeat courses were given at 21-day
      intervals. De-escalation was based primarily on myelosuppression. All patients
      received recombinant human granulocyte colony-stimulating factor to minimize the
      risk of neutropenic fever. The primary goal of the study was tumor response. In
      the trial, which is ongoing, 42 patients have been assessed to date.
      Adenocarcinoma was the predominant histology in 30 patients, while epidermoid
      cancer was seen in 13 patients. Paclitaxel was identified as an active agent.
      Thirty percent of patients with adenocarcinoma and 25% of the smaller group with
      epidermoid carcinoma have had partial remissions. Complete remissions have not
      been seen to date. The median duration of response was 9 weeks. The major
      toxicity was myelosuppression; 11 patients required admission for neutropenic
      fever on 13 different occasions. Paclitaxel is an active drug in the treatment of
      esophageal cancer. Currently, there does not appear to be a difference in
      response on the basis of histologic subtype. Further studies with paclitaxel in
      combination with other drugs (eg, cisplatin and 5-fluorouracil), on different
      treatment schedules, and as part of multimodality therapy are indicated.

PMID- 7524163
TI  - Ion channels of microbes.

PMID- 7524162
TI  - Medico-legal and ethical problems associated with treatment of children born with
      congenital malformations.
AB  - Recent advances in medicine and biomedical science have brought in their wake a
      whole array of moral, ethical and medico-legal problems. For eg, in relation to
      the withholding or withdrawal of treatment of neonates born with congenital
      malformations. While the technology to treat and thus to artificially prolong
      life is available, the related question of whether or not to do so and in what
      circumstances has to be considered. There is a paucity of cases in the courts.
      However, some useful principles can be drawn from a number of cases in the UK.
      The search for clearer legal and moral criteria has become more urgent. A way
      ahead appears to lie in the formation of Hospital Review Committees or some such
      mechanism which would enable the most appropriate decision to be taken in any one
      case bearing in mind the complex ethical and medico-legal issues involved.

PMID- 7524164
TI  - Using sequence homology to analyze the structure and function of voltage-gated
      ion channel proteins.
AB  - Molecular modeling and mutagenesis analysis of voltage-gated channels have
      succeeded in identifying much of the topology of the proteins and in identifying
      which sequential segments are involved in functional mechanisms such as
      activation gating, inactivation gating, ion selectivity, and ligand binding.
      Efforts are currently underway to use these methods to model the protein
      structure and functional mechanisms more precisely. The experimental and
      theoretical efforts are dependent to a considerable extent upon information
      obtained by comparing homologous sequences. Although the fine details of models
      developed in this manner are unlikely to be as correct as models developed from x
      ray crystallography and NMR, they still may contribute substantially to our
      understanding of the structure and function of these important proteins.

PMID- 7524165
TI  - Retroviral reverse transcriptase inhibitory activity in Thai herbs and spices:
      screening with Moloney murine leukemia viral enzyme.
AB  - Fifty-seven Thai herbs and spices were examined for their retroviral reverse
      transcriptase inhibitory activity. All herbs and spices were extracted with hot
      water and methanol. Reverse transcriptase inhibitory activity of the extracts was
      determined by using Moloney Murine Leukemia Virus reverse transcriptase (M-MuLV
      RT) reacted with 3H-dTTP and radioactivity measured with a scintillation counter.
      Eighty-one per cent (46/57) of hot-water extracts and 54% (31/57) of methanol
      extracts showed inhibitory activities. At a concentration of 125 micrograms/ml,
      13% (6/46) of hot-water extracts, namely Eugenia caryophyllus Bullock et
      Harrison, Phyllanthus urinaria Linn., Terminalia belerica Roxb., Nelumbo nucifera
      Gaertn., Psidium guajava Linn. and Lawsonia inermis Linn., had a relative
      inhibitory ratio (IR) over 50%. They showed ratios of 100%, 91%, 75%, 74%, 61%
      and 60%, respectively. For methanol extracts, only 10% (3/31) had IR values over
      50%. They were T. belerica, E. caryophyllus and N. nucifera which exhibited IR
      values of 83%, 54% and 54%, respectively.

PMID- 7524166
TI  - [Evaluation of laparoscopic and laparotomy cholecystectomy by comparing the
      dynamics of acute phase proteins].
AB  - The authors investigated in two groups of surgical patients subjected to
      laparoscopic (n = 10) and laparotomic (n = 10) cholecystectomy changes in the
      levels of nine acute stage proteins. The objective was to evaluate the extent of
      surgical stress of the two surgical procedures with regard to changes of serum
      levels of albumin, transfirrin, prealbumin, alpha 1-antitrypsin, alpha 1-acid
      glycoprotein, alpha 2-macroglobulin, haptoglobin, ceruloplasmin and C-reactive
      protein. Before operation no significant differences (p < 0.05) were found
      between the investigated indicators. Changes of acute stage proteins up to the
      third day following surgery indicate a lower surgical trauma and more favourable
      course during the early postoperative period in patients operated by the
      laparoscopic route.

PMID- 7524167
TI  - [An instrument for hepatic artery compression in palliative treatment of liver
      metastases using repeated ischemia. A model and experimental study].
AB  - Method of interrupted ischaemization of the liver afflicted with metastases from
      colorectal cancer is not definitively evaluated yet. Using the literary reports
      the authors proposed (in cooperation with MEDIN) a instrument for compression of
      the liver artery, economically easy available. The reability of this instrument
      was tested in model conditions and his safety to the tested artery was proved on
      the experimental animal.

PMID- 7524168
TI  - [Importance of the pre-donation epidemiological survey to detect donors with a
      risk of transmitting HCV].
AB  - PURPOSE: To determine if the investigation of previous clinical features through
      an inquiry could be useful to predict HCV infection in blood donors as assessed
      by recombinant immunoblot assay. MATERIAL AND METHODS: From january 1990 to
      august 1991, 79 HCV seropositive blood donors by recombinant immunoblot assays
      (58 RIBA 1 and 21 RIBA II) were selected to be inquired and to perform a clinical
      examination. The inquiry included the following parameters: age, sex, social
      environment, history of liver disease, presence or absence for parenteral risk
      factors (surgery, blood transfusion, odontological procedures, acupuncture,
      tattoos, etc...). RESULTS: 1) General data: mean age, 43 years (range 20-65);
      male/female 54/25 (ratio 2.16); urban/rural environment 50/29 (ratio 1.72);
      new/regular blood donors 17/62 (ratio 0.27). 2) Inquiry results: In seven cases
      (8.9%) previous symptoms were detected. Hepatic stigmata were present in 12
      donors (15.2%). A 67.0 showed previous surgical procedures; 48.1% had
      odontological history; 24.0% were recipients for blood transfusion; parenteral
      treatment using nondisposable material were detected in 19 cases (24.0%);
      acupuncture in 4 donors (5.0%); tattoos in only one case. Social habits were:
      alcoholic consumption in 44.3% and regular medicine ingestion in 19.0%; a 81.0%
      had a unique partner and a 8.9% preferred multiple heterosexual contacts. A 29.1%
      inhabit in unfamiliar house and the remaining 70.9% lived in apartments
      buildings; the mean of family members was 3.7 persons (range 2-8). REMARKS: a) It
      is pointed out the scarce and physical expression of the HCV infection. So in
      many aspects the inquiry is useless and time consuming. b) Nevertheless, we have
      detected some parenteral risk factors in seropositive cases. Regarding this
      particular aspect the inquiry is useful. Taken into account the previous we
      suggest to add an item with the parenteral risk factors to the ordinary self
      answering inquire, addressed to all blood donors in each donation.

PMID- 7524169
TI  - [Acquired hemoglobin H disease associated with a myelodysplastic syndrome].
AB  - Some patients found to have clonal panmyelopathies develop an acquired defect of
      haemoglobin synthesis clinically similar to haemoglobin H disease. A 58 year-old
      male diagnosed of simple refractory anaemia developed microcytosis and
      hypochromia. At the same time, his myelodysplastic syndrome became a refractory
      anaemia with excess of blasts. 33% of the red blood cells had "golf ball"
      inclusions after incubation with brilliant cresyl blue. Cellulose acetate
      electrophoresis revealed an haemoglobin H band. The globin chain synthesis
      alpha/beta ratio was 0.69. The molecular analysis demonstrated the integrity of
      both alpha genes in each chromosome. There were no familiar antecedent of
      haemoglobinopathy.

PMID- 7524170
TI  - [Hepatitis-C-positive mixed essential cryoglobulinemia, autoimmune hemolytic
      anemia, and immune thrombocytopenic purpura].

PMID- 7524171
TI  - [Agranulocytosis caused by ticlopidine].

PMID- 7524172
TI  - Mast cell-rich convexity meningioma presenting as chronic subdural hematoma: case
      report and review of the literature.
AB  - A 47-year-old woman with a convexity meningioma presenting as a chronic subdural
      hematoma is reported. This case is unique in that the symptoms were cyclical and
      stereotypic. The tumor contained an unusually high number of mast cells. A
      possible etiologic role of histamine-related vasodilation and tumoral hemorrhage
      is explored. The relationship between meningioma and subdural hematoma is
      discussed, and the literature is reviewed.

PMID- 7524173
TI  - [A retrospective analysis of the treatment results in Hodgkin's disease in a
      radiotherapy clinic].
AB  - PURPOSE: Treatment results were reviewed in a retrospective analysis and compared
      with literature data. Prognostic factors for freedom from relapse and overall
      survival were identified. PATIENTS AND METHODS: We analyzed the history of 183
      patients treated for Hodgkin's disease between 1977 and 1989 at the Department of
      Radiation Therapy at the University of Wurzburg. There were 100 males and 83
      females between 16 and 86 years of age. 70.5% of patients presented with early
      stage Hodgkin's disease (23.5% stage I and 47.0% stage II) and 29.5% had advanced
      stages (25.1% stage III and 4.4% stage IV). All patients were treated initially
      with radiotherapy, 114 had radiotherapy alone and 69 patients received combined
      modality treatment. RESULTS: Hundred and sixty-one patients (88.0%) reached a
      complete remission. Freedom from relapse was 73.7% at 5 years and 70.3% at 10
      years for these patients, overall survival was 74.3% and 62.8% at 5 and 10 years
      for all patients. Prognostic factors for freedom from relapse were stage IV, B
      symptoms, age greater than 35 years and more than 3 involved lymph node regions.
      These factors also were relevant for overall survival, in addition mixed
      cellularity or lymphocyte depleted subtype, high erythrocyte sedimentation rate,
      failure to achieve a complete remission following initial treatment and relapse
      of Hodgkin's disease were identified as negative prognostic factors. Laparotomy
      staged patients who received radiotherapy only for stage I and II Hodgkin's
      disease had better outcome than clinically staged patients. Our data suggest that
      adequate therapy is able to reduce the impact of unfavourable prognostic factors.
      The outcome for patients with bulky mediastinal disease was similar to that in
      patients without a mediastinal mass. CONCLUSIONS: The optimal choice of treatment
      for patients with early stage Hodgkin's disease--combined modality
      treatment/radiotherapy alone/chemotherapy alone?--and for patients with advanced
      stages--consolidation radiotherapy?--remains an unresolved issue and needs
      further testing in large randomized trials considering acute and late
      complications. Staging laparotomy may be used only for a small group of patients
      who would receive radiotherapy alone as definitive treatment. Modifications of
      therapy clearly reduce the impact of negative prognostic factors.

PMID- 7524174
TI  - Treatment of muscle invasive bladder cancer. Is there a role for neoadjuvant
      chemotherapy?
AB  - PURPOSE: Because 5-year survival with advanced bladder cancer is still poor, the
      search for optimal treatment continues as dose the necessity of clarifying goals
      of treatment. PATIENTS AND METHODS: We compared the outcome of 3 different but
      widely accepted treatment protocols for bladder cancer in order to find which, if
      any, was superior, with particular emphasis upon the performance of the newest
      treatment, neoadjuvant chemotherapy. Data on 224 bladder patients treated at our
      institution (1975 to 1991) with 1 of the 3 protocols was analyzed. Those
      protocols were: 1. radiotherapy > 60 Gy (143 patients); 2. low dose radiotherapy
      followed by cystectomy (25 patients); 3. chemotherapy followed by either
      definitive radiotherapy or surgery (56 patients). Because the latter group was
      also a chronologically newer group with a shorter possible follow-up, we compared
      all treatments on the basis of 2-year survival, using Kaplan-Meier life tables.
      We briefly reviewed those modalities which are bladder-sparing because of the
      significance to quality of life of this factor. RESULTS: Two-year survival
      figures for the patients were: 63% for those who received only radiotherapy; 72%
      for those undergoing cystectomy: 68% for the group to whom neoadjuvant
      chemotherapy was administered. The differences were not statistically
      significant. However, 23% of those patients treated neoadjuvantly were alive with
      intact bladders at 2 years. CONCLUSION: These results do not suggest that a
      superior survival advantage is associated with any of these 3 protocols and
      neoadjuvant chemotherapy, in particular, cannot be seen as conferring a new and
      important survival advantage. However, neoadjuvant chemotherapy followed by
      radiotherapy does permit bladder conservation and, given that life span will
      often be reduced, the importance of helping to keep the remainder of the
      patient's life as comfortable as possible, can hardly be overestimated.

PMID- 7524175
TI  - Pancreatic enzyme elevations after blunt trauma.
AB  - BACKGROUND: Elevations in levels of the pancreatic enzymes amylase and lipase
      occur frequently after trauma. The purpose of this prospective study was to
      examine the incidence of these enzyme elevations in patients suffering blunt
      trauma, their natural history, and their relationship to posttraumatic
      pancreatitis. METHODS: One hundred consecutive trauma patients were studied on
      admission to the surgical intensive care unit with daily serum amylase and lipase
      measurements, which were blinded to the clinical service. If the enzyme levels
      were elevated after 3 days, the patient was enrolled in the study and observed
      and examined daily, and enzyme levels were measured every other day. These
      patients were fed enterally by the clinical service if no symptoms of clinical
      pancreatitis were present. RESULTS: In 17% of patients persistent pancreatic
      enzyme elevations developed. These patients more frequently had had hypotension,
      higher Injury Severity Scores, and were more likely to have had severe head
      injuries than those whose enzyme levels remained normal. Five percent of those
      studied displayed evidence of clinical pancreatitis, and none of these patients
      had only isolated head injuries. Lumbar spine injuries and retroperitoneal
      hematomas were present more frequently in the group in whom symptomatic
      pancreatitis developed. CONCLUSIONS: After blunt trauma 17% of patients displayed
      persistent pancreatic enzyme elevations, but the majority remained asymptomatic
      despite enteral feeding. Retroperitoneal injury may identify patients at risk for
      pancreatitis. Patients with isolated head injuries should be fed enterally.

PMID- 7524177
TI  - [Education--practice offer to Mette].

PMID- 7524178
TI  - [Palliative treatment--possibilities for alleviation].

PMID- 7524176
TI  - Granulocyte colony-stimulating factor prophylaxis before operation protects
      against lethal consequences of postoperative peritonitis.
AB  - BACKGROUND: Postoperative peritonitis has a high mortality in human beings. It is
      accepted that cytokines are important mediators in pathophysiology of sepsis. The
      recent failure of clinical trials increased the necessity to proof new drugs in
      more clinically relevant animal models. The aim of this study was to examine the
      effect of granulocyte colony-stimulating factor (G-CSF) in addition to an
      antibiotic in postoperative peritonitis. METHODS: Dose-response curves and
      experimental conditions were developed in a total of 295 rats. The main
      experiment included three groups: control animals receiving a fecal inoculum, a
      group treated with antibiotic, and a third group receiving G-CSF in addition to
      the antibiotic. The main outcome was death, but in addition, serum tumor necrosis
      factor (TNF) level was determined. RESULTS: The mortality rate of 60% in
      antibiotic treated animals was considerably reduced by G-CSF to 20%. All animals
      of the control group died during the observation period of 120 hours. A
      correlation between TNF levels and mortality rate was observed. In G-CSF treated
      animals total suppression of TNF serum levels was accessible in contrast to the
      others. CONCLUSIONS: In a clinically relevant animal model G-CSF was effective as
      an additional concept of prophylaxis. These data are promising toward clinical
      trials.

PMID- 7524181
TI  - [Palliative treatment--radiation against pain and pressure].

PMID- 7524179
TI  - [Palliative treatment--pain relief in the terminal stage].

PMID- 7524183
TI  - [Palliative treatment--prednisone for symptoms].

PMID- 7524180
TI  - [Palliative treatment--adverse effects should be mild].

PMID- 7524185
TI  - [Memory--seen with Danish eyes].

PMID- 7524182
TI  - [Palliative treatment--relief with hormones].

PMID- 7524186
TI  - The HLA-B73 antigen has a most unusual structure that defines a second lineage of
      HLA-B alleles.
AB  - The nucleotide sequence of cDNA encoding the HLA-B73 antigen was determined; it
      is unusually divergent, differing from other HLA-B alleles by 44-77 nucleotide
      substitutions. Features that distinguish the B*7301 heavy chain from other HLA-B
      heavy chains include multiple substitutions in the alpha 3 domain and a
      duplication-deletion within the transmembrane region that increases the length of
      B*7301 compared to other HLA-B heavy chains. The duplication-deletion is shared
      with subsets of B alleles from the homologous gorilla (Gogo-B) and chimpanzee
      (Patr-B) loci. Other unusual features of B*7301 are individually shared with
      certain alleles of the HLA-A, HLA-C, HLA-F, Gogo-B and Patr-B loci. The B*7301
      molecules has sequence elements in common with members of the B7 crossreacting
      group in the alpha 1 domain and is shown to possess the ME1 epitope, which is
      held in common with the B7, B22, B27, B42 and B67 antigens. B*7301 has a unique
      cysteine at position 270 of the alpha 3 domain which appears accessible but
      probably does not form disulphide-bonded B*7301 dimers in cell membranes. B*7301
      represents a newly discovered but ancient lineage of HLA-B alleles that appears
      poorly represented in the modern human population.

PMID- 7524184
TI  - [Palliative treatment--when life is about to be over].

PMID- 7524187
TI  - Derivation and application of monoclonal antibodies recognizing several epitopes
      on bovine serum albumin.
AB  - Three (AB-3, AB-4 and AB-6) monoclonal antibodies (mAb) to bovine serum albumin
      (BSA) were derived and characterized for their physicochemical and immunological
      properties. AB-3 recognized an epitope distinct from epitopes recognized by AB-4
      and AB-6 as determined by binding inhibition assay. AB-4 and AB-6 mAbs recognized
      similar but not identical epitopes on BSA. Based on the antigenic specificity, we
      applied these mAbs to quantitative analysis of BSA in medium and to depletion of
      BSA from culture medium containing fetal calf serum (FCS). For quantitative
      analysis, we employed a sandwich enzyme-linked immunosorbent assay (ELISA) using
      biotinylated AB-3, solid-phase of AB-6 and an avidin-biotin-peroxidase complex
      system. This assay was highly sensitive and quantitative in the range of BSA
      concentration at 10 to 1,500 ng/ml. To deplete BSA from medium, we prepared
      affinity-gel coupled to AB-6. Repeated treatment of FCS-containing medium with
      the affinity-gel efficiently depleted BSA from the medium. The depletion capacity
      was 0.74 to 1.0 moles of BSA/mole of coupled mAb.

PMID- 7524188
TI  - Chronic exposure to simulated altitude does not increase angiogenic activity in
      skeletal muscle of rats.
AB  - In order to examine whether the hypoxia of high altitude increases angiogenic
      activity in skeletal muscle, six male Wistar rats were subjected to a simulated
      altitude of about 5,500 m (ambient pressure 380 mmHg) for 3 weeks, and the whole
      soleus, gastrocnemius, and extensor digitorum longus muscles were collected. As a
      result, any muscle extracts from high altitude rats did not significantly enhance
      the capillary growth in an in vitro angiogenesis model compared with those from
      sea-level rats. This appeared to confirm previous morphological studies that
      hypobaric-hypoxic environment did not cause the formation of new capillaries in
      skeletal muscles.

PMID- 7524189
TI  - Endothelin receptor density in human hypertrophic and non-hypertrophic prostate
      tissue.
AB  - The amount of endothelin receptors in human prostate tissue was measured by
      radioligand binding techniques using 125I-Endothelin -1 and -3 (125I-ET-1, -3).
      Specimens of the non-hypertrophy group were obtained from 6 patients who
      underwent total cystectomy under the diagnosis of bladder cancer and those of the
      hypertrophy group from 6 prostatic hypertrophy patients who underwent open
      prostatectomy. 125I-ET-1 bound to the prostate tissue with the KD value of 0.033
      +/- 0.012 nM in the non-hypertrophy group and with the KD value of 0.035 +/-
      0.012 nM in the hypertrophy group. 125I-ET-3 bound to the prostate tissue with
      the KD value of 0.023 +/- 0.011 nM in the non-hypertrophy group and with the KD
      value of 0.029 +/- 0.016 nM in the hypertrophy group. The KD values were not
      significantly different between the hypertrophy and non-hypertrophy groups. The
      KD values of 125I-ET-1 and 125I-ET-3 were similar. The Bmax values (fmol/mg
      protein) of 125I-ET-1 binding to the prostate tissue were 32.18 +/- 3.69 to the
      non-hypertrophy group and 85.66 +/- 20.65 to the hypertrophy group. The Bmax
      values (fmol/mg protein) of 125I-ET-3 binding to the prostate tissue were 27.48
      +/- 5.25 to the non-hypertrophy group and 75.90 +/- 13.46 to the hypertrophy
      group. The Bmax values of both 125I-ET-1 and 125I-ET-3 were significantly higher
      in the hypertrophy group than in the non-hypertrophy group.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7524190
TI  - B cells are required as APC for antigen-specific T cell proliferation but not for
      the differentiation or priming of those T cells.
AB  - We studied the influences of B cells on functional differentiation of T cells
      using SCID mice grafted with fetal thymus of C.B-17 mice (TG mice). T cells were
      shown to be reconstituted in TG mice without B cell development. These mice
      showed normal DTH response to SRBC and OVA. LN cells of these mice produced
      cytokines including IL-2, IL-4, IL-6 and IFN-gamma according to Con A
      stimulation. Thus, majority of T cell functions seem to differentiate in the
      absence of B cells. However, T cells of TG mice failed to proliferate in response
      to immunizing antigens in vitro, although they responded well to stimulation with
      Con A. This unresponsiveness of T cells in TG mice to these antigens was restored
      when antigen-primed B cells were added to the proliferation assay. Such an
      inability of T cells in antigen-specific proliferation was not seen in SCID mice
      grafted with C.B-17 fetal liver cells, in which B cells as well as T cells were
      efficiently reconstituted (FLT mice). T cell proliferation to immunizing antigen
      was also abrogated in FLT mice when B cells were depleted from lymphoid
      population. These results indicate that T cells can functionally differentiate
      and be primed in the absence of B cells, but they require B cells to proliferate
      in response to foreign antigens.

PMID- 7524191
TI  - Virological features of hepatitis C virus infection in patients with liver
      diseases in the inshore area of the Yangtze River.
AB  - The prevalence, genotypes, coinfection and putative core gene sequence of
      hepatitis C virus (HCV) were investigated in the inshore area of the Yangtze
      River, where hepatocellular carcinoma (HCC) is thought to be very common. Most
      patients with liver diseases were infected with hepatitis B virus (HBV), but the
      incidence of anti-HCV was very low, being 3.4% in patients with acute hepatitis,
      and approximately 7% in those with chronic liver diseases. The rate of
      coinfection with HBV and HCV in patients with HCC was 4.5%, which was similar to
      that in Shanghai (5.6%), but lower than that in Yangzhou (31.2%), Beijing (26.8%)
      and Zhejiang (28.6%). Of 124 patients with non-A, non-B (NANB) liver disease, 15
      (12.1%) were positive for anti-HCV. HCV genotype analysis in 41 HCV-RNA-positive
      patients with liver diseases showed that genotype II was dominant (85.4%),
      followed by genotype III (7.3%) and II+III (7.3%). No genotype I or IV was found.
      The genome sequences of the HCV putative core gene from two patients with chronic
      hepatitis were more closely similar to those of previous isolates from Japan and
      China, than to that of an American isolate. These results suggest that HCV
      infection is not an important etiological factor for liver diseases, and that the
      HCV isolates in China are from the same subgroup as those in Japan.

PMID- 7524192
TI  - The efficiency of solvent extraction of mutagenic compounds in particulates
      exhausted from a small diesel engine.
AB  - Organic materials were extracted from particulates exhausted from a small diesel
      engine (displacement 269 ml) by the ultrasonic extraction method with three
      different solvent systems, methanol, dichloromethane and a 4:1 (v:v) mixture of
      benzene and ethanol. These solvent-extracted materials were tested for mutagenic
      activity by the Ames Salmonella/microsome assay system using Salmonella
      typhimurium strains TA98, TA100, TA98NR and TA98/1,8-DNP6. The concentrations of
      1-nitropyrene (1-NP) and 1,6-dinitropyrene (1,6-diNP) in these extracted
      materials were also measured after nitroreduction by high pressure liquid
      chromatography. The methanol-extracted and benzene-ethanol-extracted materials
      showed the lowest and the highest mutagenic activity, respectively. The methanol
      extracted, dichloromethane-extracted and benzene-ethanol-extracted materials
      induced 260, 1,570 and 3,240 His+ revertants per plate per mg of extracted
      materials, respectively, from strain TA98 in the absence of S9 mix. These
      materials showed decreased mutagenicity for strains TA98NR and TA98/1,8-DNP6,
      indicating that the particulates in the diesel engine exhaust contained 1-NP and
      diNPs. Actually, the amount of 1-NP and 1,6-diNP in the methanol-extracted,
      dichloromethane-extracted and benzene-ethanol-extracted materials were 17.0 and
      0.03 ng, 37.5 and 0.97 ng, and 71.3 and 1.03 ng per mg of extracted materials,
      respectively, accounting for 11.9 and 3.2%, 4.4 and 17.3%, and 4.0 and 8.9%,
      respectively, of the total mutagenicity of the extracted materials. From these
      results it is concluded that a mixture of benzene-ethanol (4:1, v/v) is the most
      suitable solvent for extraction of organic matter containing nitrated polycyclic
      aromatic hydrocarbons such as NPs from particulates in diesel engine exhaust.

PMID- 7524193
TI  - Prevalence of HCV-antibodies and HCV-RNA in donor blood in Tokushima Prefecture.
AB  - The incidence of C100-3 among the blood specimens qualified for transfusion
      according to the conventional criteria was 1.1%. The incidence of C100-3 in donor
      blood in Tokushima Prefecture is not significantly different from that reported
      for all Japan. Of the donors positive for the conventional screening test and
      C100-3, 73.6% showed high ALT levels. For all antibodies, the incidence of HCV
      RNA was very low in the donors positive for a single antibody, but was high in
      those positive for multiple antibodies. All of the donors showing the 3
      antibodies were positive for HCV-RNA. While a test for multiple antibodies is
      thought to be effective for the screening of HCV, more blood needs to be
      discarded, having a serious cost-performance problem. The O.D. value for C100-3
      and the 2nd antibody seem to be useful reference value for antibody titers.

PMID- 7524195
TI  - Cadmium uptake by kidney distal convoluted tubule cells.
AB  - Cadmium is transported by and accumulated in the kidney, which is a primary site
      of its toxicity. Most cadmium is reabsorbed and accumulated by proximal tubules.
      However, evidence for distal tubule toxicity suggests that transport may also
      proceed at that nephron site. Therefore, we measured cadmium uptake by an
      immortalized distal convoluted tubule (DCT) cell line. Absolute rates of cadmium
      uptake averaged 0.43 nmol min-1 mg protein-1, about 20% of the rate of calcium
      uptake, at an extracellular calcium ([Ca]o) concentration of 1 mM. As [Ca]o was
      reduced below 1 mM, cadmium uptake increased in a stepwise fashion. When [Ca]o
      was raised above 1 mM, cadmium uptake diminished proportionately. These results
      support the view that calcium and cadmium compete for the same transport
      mechanism in DCT cells. We also examined the interaction of cadmium on cadmium
      uptake, as well as the effects of selected di- and trivalent cations on cadmium
      transport. The resulting inhibitory sequence was Fe > La = Mn > Co > Cu = Mg > Zn
      > Cd > Ni = Sr > Ca. Bay k 8644 enhanced and nifedipine abolished cadmium uptake
      that was stimulated by parathyroid hormone (PTH). However, neither Bay k 8644 nor
      nifedipine altered basal cadmium uptake. We conclude that cadmium is taken up by
      distal convoluted tubule cells. Under resting conditions cadmium entry is
      mediated by a mechanism that is insensitive to calcium channel agonists or
      antagonists. Cadmium entry stimulated by PTH is mediated by dihydropyridine
      sensitive calcium channels.

PMID- 7524194
TI  - Effects of ethylnitrosourea on expression of proto-oncogene pp60c-src and high
      molecular-weight neurofilament protein in rodent embryo central nervous system
      cells in vitro.
AB  - Effects of exposure to ethylnitrosourea (ENU) on expression of proteins that play
      a role in neuronal differentiation were examined in central nervous system (CNS)
      micromass embryo cell cultures. ENU is a known developmental toxicant which
      affects neuronal development. The proteins selected were the protein product of
      the src proto-oncogene (pp60c-src) and high-molecular-weight neurofilament
      protein (NF). pp60c-src has marked increases in amount and kinase activity in
      neurons at the time of differentiation and NF is found in differentiated neurons.
      CNS micromass cultures are primary cells from Day 12 rat embryo midbrains which
      are plated at high density and differentiate into neurons during 5 days in
      culture. Proteins were quantitated by polyacrylamide gel electrophoresis
      separation of equal amounts of total cell protein followed by transfer to
      membranes, immunoblotting, and densitometric scanning of blots. Dose-dependent
      decreases in cell growth and differentiation were confirmed using endpoints of
      cell number, protein content of cultures, neutral red uptake, hematoxylin
      staining of differentiated cells, and levels of binding of the neurotransmitter
      [3H]gamma-aminobutyric acid. Concentrations which inhibited response by 50%
      compared to controls ranged from 232 to 455 microM ENU. Dose-related decreases in
      amounts of pp60c-src and NF proteins relative to total protein were seen in CNS
      cultures treated with ENU. Results confirm the usefulness of the micromass
      cultures in following chemical effects on neuronal differentiation. The effects
      of ENU on specific proteins associated with neuronal differentiation were shown.

PMID- 7524196
TI  - Studies on the correlation between blood cholinesterase inhibition and 'target
      tissue' inhibition in pesticide-treated rats.
AB  - Inhibition of cholinesterase activity in the blood has been proposed as an index
      of ChE activity in tissues targeted by ChE-inhibiting pesticides, including the
      muscle end-plate region and the central nervous system (CNS). While opinions vary
      regarding the utility of blood ChE activity in predicting ChE activity in the
      target tissues, there appear to be no comprehensive studies designed to assess
      this possible correlation in a time- and dose-dependent manner. We undertook this
      type of study by administering a single dose of an organophosphate, chlorpyrifos
      (0, 30, 60 or 125 mg/kg in corn oil, s.c.) to rats and then sacrificing animals
      at 1, 4, 7, 21 or 35 days after dosing. Whole blood, plasma, erythrocytes,
      frontal cortex, hippocampus, striatum, hypothalamus and diaphragm tissue were
      collected and assayed for ChE activity. Collapsed across dosages, optimal
      correlations of blood ChE activity with brain or muscle activity occurred 7-21
      days after dosing (when ChE inhibition was maximal and most stable). At all times
      after dosing, there was a high correlation among ChE activity in the hippocampus,
      striatum and frontal cortex. Generally, ChE activity in whole blood and
      erythrocytes correlated better with the activity in brain and muscle than did
      activity in the plasma (whole blood > or = erythrocytes >> plasma). Similar
      relationships were also observed in a more abbreviated study using a direct
      acting organophosphate, paraoxon. ChE activity was determined in blood
      components, brain and muscle at the time of maximal inhibition (4 h after
      injection) and during recovery (24 hrs after injection) using two dosage levels
      (0.17 or 0.34 mg/kg, s.c.). Taken together, these data indicate that the level of
      ChE activity in the blood may accurately reflect activity in other tissues, but
      that this correlation is tissue- and time-specific.

PMID- 7524197
TI  - Lindane does not alter the estrogen receptor or the estrogen-dependent induction
      of progesterone receptors in sexually immature or ovariectomized adult rats.
AB  - Lindane, gamma-1,2,3,4,5,6-hexachlorocyclohexane (gamma-HCH), has been shown to
      disrupt reproductive function in mammals. Many of these adverse effects on female
      reproduction such as alterations in sexual receptivity, disrupted ovarian
      cyclicity, reduction in uterine weight and termination of pregnancy are thought
      to be due to altered ovarian hormone secretions and/or an impaired response to
      circulating estrogen. It has been suggested that gamma-HCH may block the response
      of estrogen-dependent tissues to estradiol via an interaction with the estrogen
      receptor. To test this hypothesis, estrogen (ER) and progesterone (PR) receptor
      affinity and number were evaluated in sexually immature, 17 beta-estradiol-3
      benzoate (EB)-primed Long Evans female rats following exposure to vehicle or
      gamma-HCH (40 mg/kg) for 7 days (Study 1) and in adult, ovariectomized EB-primed
      Long-Evans rats following gavage with vehicle or gamma-HCH (0, 10, 20, or 40
      mg/kg) for 5 days (Study 2). Chlordecone (kepone; 40 mg/kg; i.p.) was used in
      Study 2 as a positive control for the alteration of the estrogen-induction of PR
      in the pituitary. Neither gamma-HCH nor chlordecone altered serum estradiol
      concentrations. gamma-HCH did not change the ER number (1, 24, or 30 h after EB)
      or the estrogen-dependent induction of PR (24 or 48 h after EB) in the
      hypothalamus (HYP), pituitary, or uterus. These data indicate that the effects of
      gamma-HCH on the female reproductive system do not involve an alteration in the
      ER and that heterogeneity exists between target tissues in their response to
      xenobiotics.

PMID- 7524199
TI  - Adjuvant effect of Loxosceles gaucho (South American brown spider) venom.
AB  - Injection of L. gaucho venom and antigens (ovalbumin, ovomucoid and bovine gamma
      globulin) into rabbit skin induced an intense local inflammatory lesion and
      resulted in a significant increase in the level of IgG antibodies to the antigen
      in both the primary and secondary humoral immune response. The adjuvant activity
      of the venom was associated with its high mol. wt components, which are
      responsible for the inflammatory lesion. Rabbits rendered unresponsive to the
      venom and injected with venom plus antigen presented a very mild local
      inflammatory reaction and no increase in antibody formation. When venom and
      antigen were injected simultaneously but at different skin sites no adjuvant
      effect was induced. However, when antigen was injected 4 hr after venom injection
      but at the same skin site a significant adjuvant effect was produced.
      Furthermore, when venom plus antigen was injected intradermally into mice, a
      species in which the venom does not cause an inflammatory skin lesion, no
      adjuvant effect was detected. It is suggested that the adjuvant effect of L.
      gaucho venom in rabbits is probably due to its ability to cause a local severe
      inflammatory reaction.

PMID- 7524200
TI  - Application of the kinetic of RNA synthesis on Hep 3B cells. Study of the medium
      term cytotoxicity of atrazine.
AB  - The test based on measuring the RNA synthesis rate, already described on Hela S3
      in culture (Fauris et al., Les colloques de l'INSERM 106 (1981) 455-463), has
      been adapted to a human hepatoma cell line Hep 3B which retains a certain
      capacity towards metabolising. These modifications make it easier to point to the
      presence of possible water micropollutions and to envisage the study of the
      medium-term toxicity of such pollutants to be found in traces in water, with
      adequate sensitivity if we take into account their low concentration level. This
      trial has been carried out to compare the cytotoxicity of atrazine, over short-
      and medium-term periods: prolonged exposure to atrazine (1 or 10 micrograms/l)
      leads to an increase in the RNA synthesis rate (not to be detected after 24 h of
      exposure). Pre-exposure to 1 or 10 micrograms/l pesticide (over 6 days) would
      cause results to increase considerably during any future intoxication (250
      micrograms/l).

PMID- 7524198
TI  - IL-4 production in mediastinal lymph node cells in mice intratracheally instilled
      with diesel exhaust particulates and antigen.
AB  - To clarify the relationship between air pollutants and IgE antibody production,
      interleukin 4 (IL-4) production was investigated in BALB/c mice intratracheally
      injected with diesel exhaust particulates (DEP) mixed with antigen (Ovalbumin
      (OA) or Japanese Cedar Pollen (JCP)). BALB/c mice were injected with DEP plus OA
      or OA alone three times with a 3-week interval. After the last instillation,
      proliferative response and lymphokine-producing activity of mediastinal lymph
      node cells (LNC) were examined in vitro. Proliferative response to OA in
      mediastinal LNC from mice injected with DEP plus OA was enhanced 4-17 times of
      that from control mice. IL-4-producing activity by OA stimulation also enhanced
      in mediastinal LNC from mice injected with DEP plus OA. A significantly larger
      amount of anti-OA IgE antibody was detected in sera from DEP- and OA-injected
      mice compared with those from control mice. The levels of IL-4, estimated by JCP
      antigen in mediastinal LNC, from mice injected with DEP plus JCP were two-fold
      higher than those from mice injected with JCP alone. These results suggest that
      intratracheal instillation of DEP affects antigen-specific IgE antibody responses
      via local T-cell activation, especially enhanced IL-4 production.

PMID- 7524201
TI  - Effect of storage and ultraviolet B irradiation on CD14-bearing antigen
      presenting cells (monocytes) in platelet concentrates.
AB  - BACKGROUND: Ultraviolet B (UVB) irradiation of platelet concentrate (PCs) reduces
      platelet alloimmunization, but the mechanism of the effect is unclear. Evidence
      suggests that UVB may downregulate the expression of surface adhesion molecules
      on passenger antigen-presenting cells in PCs. STUDY DESIGN AND METHODS: The
      effect of blood bank storage, platelet preparation from whole blood, and UVB
      irradiation on the quantitative expression of intercellular adhesion molecule-1
      (ICAM-1, or CD54), HLA-DR, CD45, and CD11c on CD14-positive antigen-presenting
      cells (monocytes) was studied by using two-color flow cytometry. RESULTS: Blood
      bank storage for 4 days resulted in upregulation of ICAM-1 and HLA-DR and
      downregulation of CD14 but left the expression of CD11c and CD45 unchanged.
      Preparation of PCs from fresh whole blood was associated with a rapid increase in
      CD11c without upregulation of ICAM-1 and HLA-DR. UVB irradiation before storage
      inhibited the upregulation of ICAM-1 and HLA-DR, resulted in accelerated
      downregulation of CD14, and was associated with increased loss of monocytes.
      Agitation of the PC bag during irradiation was of critical importance, since
      omission of agitation resulted in largely uninhibited upregulation of ICAM-1 but
      was still associated with significantly higher cell loss than that seen in
      unirradiated controls. CONCLUSION: UVB exposure nonspecifically affects monocytes
      in PCs, resulting in downregulation of surface molecules that are important for
      antigen presentation, as well as in significant cell loss.

PMID- 7524202
TI  - Cyclosporine increases the oxidizability of low-density lipoproteins in renal
      transplant recipients.
AB  - Blood specimens from twenty-six renal transplant recipients treated with
      cyclosporine (CsA) were collected at weekly intervals, two months after
      transplantation. Specimens were grouped according to their CsA concentrations.
      Group I consisted of ten specimens with CsA concentration of >400 ng/ml; group II
      consisted of ten specimens with CsA concentrations ranging from 120-300 ng/ml;
      and group III consisted of six specimens with CsA concentrations of < 100 ng/ml.
      In addition, specimens from five renal transplant patients who, instead of CsA,
      received the immunosuppressant FK506 (group IV), and from six healty individuals
      were included. Plasma low-density lipoproteins (LDL) were isolated and their
      susceptibility to oxidation was studied by continuously monitoring the formation
      of conjugated dienes during copper ion-mediated oxidation. Patients with higher
      blood concentrations of CsA (groups I and II) had significantly higher
      oxidizability of LDL, as indicated by the shorter time required to start the
      oxidation (lag phase). The oxidizability of samples with low concentration of CsA
      (group III) was not significantly different from that of FK506-treated patients
      or healthy individuals. There was a negative correlation (r = -0702, P < 0.01)
      between oxidizability (lag phase) and CsA concentration in LDL. No correlation
      between blood CsA and plasma cholesterol or triglyceride concentration was
      evident during a three-month period postoperatively. Similarly, no correlation
      between the degree of oxidizability and plasma cholesterol or triglycerides was
      found at the time of the experiment. These findings suggest a prooxidant effect
      of CsA to plasma LDL, and may indicate that CsA is an important risk factor in
      the accelerated atherosclerosis of renal transplant recipients.

PMID- 7524203
TI  - The effect of FK506 versus cyclosporine on glucose and lipid metabolism--a
      randomized trial.
AB  - In order to evaluate the effect of cyclosporine (CsA) versus FK506 on glucose and
      lipid metabolism, an oral glucose tolerance test (OGTT) was performed in 101
      patients after orthotopic liver transplantation (OLT) (mean interval after OLT:
      511 days). The liver graft recipients had been randomized prospectively to two
      groups prior to OLT to receive either immunosuppression with CsA, azathioprine,
      and corticosteroids (CsA group) or FK506 and corticosteroids (FK group). Along
      with the OGTT, serum insulin, insulin C-peptide and glucagon as well as serum
      lipids were monitored. There was no statistically significant difference in the
      occurrence of impaired glucose tolerance (IGT) or manifest diabetes mellitus
      disease between the two groups. In fact, not a single patient developed new-onset
      diabetes in any group. In male and female patients, serum levels of cholesterol
      and triglycerides increased significantly under FK506 and CsA treatment after
      OLT. Cholesterol was significantly higher in the CsA group in men, in women this
      was marked, but not significant. While triglycerides were significantly higher in
      women on CsA treatment, there was no such difference in men. In conclusion, both
      CsA and FK506 proved to have similar effects on glucose metabolism, while there
      was a different spectrum of serum lipid alterations.

PMID- 7524204
TI  - Infectious complications in liver transplant recipients on tacrolimus.
      Prospective analysis of 88 consecutive liver transplants.
AB  - This prospective study characterizes the incidence, etiology, timing, risk
      factors, and outcome of the infectious complications after 88 consecutive liver
      transplantations in 79 patients receiving tacrolimus (FK506) as primary
      immunosuppression with a median follow-up of 880 days. Infections occurred in 59%
      (47/79) of the patients, and 39% had major infections. Of the major infections,
      55% were bacterial, 22% were viral, and 22% were fungal. Bacteremia accounted for
      30% of major bacterial infections. Sixty percent of bacteremias occurring within
      the first 3 months were catheter related, while 75% of those occurring more than
      3 months after transplant were of a biliary source. Patients with recurrent
      hepatitis C virus hepatitis and patients requiring dialysis after transplant had
      a significantly higher rate of infections as compared with other patients.
      Overall mortality was 18%, and 29% of all deaths were associated with infection.
      Only invasive aspergillosis was associated with infectious mortality. Our data
      suggest that the potent immunosuppressive agent FK506 is not associated with a
      higher incidence of infectious complications as compared with previous studies
      using CsA.

PMID- 7524205
TI  - The extent of peritubular CD14 staining in renal allografts as an independent
      immunohistological marker for acute rejection.
AB  - Previously, we demonstrated that in acute interstitial rejection,
      immunohistological staining of renal allograft biopsies with the CD14 mAb WT14,
      reacting with human monocytes/macrophages, shows a characteristic peritubular
      increase of positive cells. To test the diagnostic value of this CD14 positivity,
      we compared, in 154 unselected renal allograft biopsies, the extent of
      peritubular WT14 staining with (a) the original histological diagnosis, made with
      knowledge of clinical data, (b) the retrospectively and blindly scored
      histological diagnosis according to the criteria of the Banff classification, and
      (c) the eventual clinical diagnosis, which included evaluation of the response to
      therapy. The extent of peritubular WT14 positivity, blindly scored on cryostat
      sections of the frozen part of the biopsies, correlated positively with the
      probability of acute rejection (AR). When using a cutoff of 70% WT14 positivity
      for the diagnosis of AR, as extracted from a receiver operating characteristic
      curve, the WT14 diagnosis had a positive predictive value of 91% and a negative
      predictive value of 56%, compared with the original histological diagnosis.
      Compared with the Banff diagnosis of AR (grade I-III), these values were 95% and
      47%, and compared with the clinical diagnosis, 84% and 63%, respectively. The
      WT14 diagnosis essentially corrected the original histological diagnosis in 7
      cases, and was consistent with the eventual diagnosis in 5 equivocal cases. We
      conclude that the extent of peritubular CD14 positivity can be used as a marker
      for AR and can serve as a valuable additional criterion for AR in the
      histological examination of renal allograft biopsies.

PMID- 7524209
TI  - Schizophrenia research moves to the prefrontal cortex.

PMID- 7524208
TI  - Assessment of soluble adhesion molecules (sICAM-1, sVCAM-1, sELAM-1) and
      complement cleavage products (sC4d, sC5b-9) in urine. Clinical monitoring of
      renal allograft recipients.
AB  - Increasing evidence exists that inducible adhesion molecules are involved in cell
      mediated allograft rejection. In addition, complement activation during rejection
      has been described. This study investigated, whether specific molecules derived
      from either pathway are excreted into urine during rejection and whether they can
      provide useful diagnostic tools for the monitoring of renal transplant
      recipients. Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM
      1, sE-selectin) and of complement cleavage products (sC4d and sC5b-9), were
      determined by standardized ELISA in 30 normal controls and 80 samples from 49
      recipients of renal allografts. In contrast to the low amounts of adhesion
      molecules and complement components uniformly excreted by healthy persons (group
      0), marked differences were observed among allograft recipients. To prove the
      clinical relevance of these differences in excretion, patient samples were
      assigned to 5 categories according to clinical and histopathological criteria:
      group I--acute steroid-resistant rejection (n = 10); group II--acute steroid
      sensitive rejection (n = 10); group III--chronic rejection (n = 23); group IV-
      stable graft function (n = 27); and group V--miscellaneous disorders (n = 10),
      including infections, CsA overdoses, and glomerulonephritis. Urinary levels of
      sICAM-1, sVCAM-1, and sC4d were significantly higher in group I compared with all
      other groups (P < 0.01). The difference in sICAM-1 excretion between groups III
      and IV also reached statistical significance (P < 0.05). Urinary concentrations
      of sICAM-1, sVCAM-1, and sC4d were reflective of their histological distribution
      in corresponding graft biopsies. None of the patients excreted E-selectin in
      detectable amounts. Excretion of the terminal membrane attack complex C5b-9 was
      not significantly associated with any diagnosis. It is concluded that for
      clinical purposes the combined evaluation of sICAM-1, sVCAM-1, and sC4d is most
      useful and can provide valuable information with regard to the severity and the
      type of allograft rejection.

PMID- 7524207
TI  - Gal alpha(1,3)Gal is the major xenoepitope expressed on pig endothelial cells
      recognized by naturally occurring cytotoxic human antibodies.
AB  - Hyperacute rejection, mediated by natural antibody, is the major barrier to
      xenotransplantation. The studies reported herein were aimed at evaluating
      antibody-mediated cytotoxicity and the role of the Gal alpha(1,3)Gal epitope,
      which we had previously demonstrated was the major epitope of pig cells detected
      by naturally occurring human antibodies. Also, we had shown that this epitope
      could be induced in non-expressing cells by the transfection of a cDNA clone
      encoding alpha(1,3)galactosyl transferase, the enzyme that produces this epitope.
      The importance of the Gal alpha(1,3)Gal epitope was supported by (1) sugar
      inhibition studies; (2) complete absorption of cytotoxic antibodies by melibiose
      sepharose columns; and (3) the ability of normal human serum to lyse COS cells
      after transfection with a cDNA clone encoding alpha(1,3)galactosyl transferase.
      These findings strongly suggest that the majority of cytotoxic human antibodies
      that would recognize a xenogeneic graft are directed to the Gal alpha(1,3)Gal
      epitope.

PMID- 7524206
TI  - Effects of transfected complement regulatory proteins, MCP, DAF, and MCP/DAE
      hybrid, on complement-mediated swine endothelial cell lysis.
AB  - We established several swine endothelial cell (SEC) lines, expressing human MCP
      (CD46), DAF (CD55), and MCP/DAF hybrid by transfection of cDNA, and assessed the
      function of these transfectant molecules on complement-mediated cell lysis as an
      in vitro hyperacute rejection model of swine to human discordant xenograft.
      Discordant organ xenografts are hyperacutely rejected by complement activation.
      Amelioration of complement-mediated lysis by these transfectant molecules was
      tested in each SEC line by lactate dehydrogenase assay. Naive swine endothelial
      cells were markedly damaged by human complement mainly via the classical pathway,
      activating only minimally the alternative pathway of human complement. Both MCP
      and DAF protected SEC from human complement attack in parallel with the
      expression density, with DAF being more effective than MCP. The MCP/DAF hybrid
      was more effective than MCP alone, and as effective as DAF in this system. The
      results suggest that the transfection of DAF or the MCP/DAF hybrid cDNA into
      organs to be transplanted could protect against hyperacute rejection.

PMID- 7524211
TI  - Visual imagery and visual representation.
AB  - Among many controversies in visual neuroscience is whether visual imagery of
      objects, scenes and living beings is based upon contributions of the early visual
      areas or depends on hierarchical higher visual areas only, and whether the
      cortical areas subserving visual imagery are identical to those underlying visual
      perception. These questions are important for furthering our understanding of
      vision, since areas active in visual imagery might tell us how the visual cortex
      represents objects, scenes and living beings. Here, P.E. Roland and B. Gulyas
      present their hypothesis, based on experimental evidence in man and primates,
      that the visual areas subserving visual imagery are parieto-occipital and temporo
      occipital visual association areas, and that these areas form only a subset of
      the visual areas engaged in perception. This hypothesis is consistent with the
      view that objects, scenes and living beings are represented, stored and re-evoked
      outside the domain of the primary visual cortex and its immediate neighbours.

PMID- 7524212
TI  - Visual imagery: an interaction between memory retrieval and focal attention.

PMID- 7524210
TI  - Localization of brain function using magnetic resonance imaging.
AB  - When nuclear magnetic resonance images (MRIs) of the brain are acquired in rapid
      succession they exhibit small differences in signal intensity in positions
      corresponding to focal areas of activation. These signal changes result from
      small differences in the magnetic resonance signal caused by variations in the
      oxygenation state of the venous vasculature. Using this non-invasive functional
      MRI (fMRI) method, it is possible to localize functional brain activation, in
      normal individuals, with an accuracy of millimeters and a temporal resolution of
      seconds. Though numerous technical challenges remain, fMRI is increasingly
      becoming a key method for understanding the topographical organization of the
      human brain.

PMID- 7524213
TI  - In search of occipital activation during visual mental imagery.

PMID- 7524214
TI  - Do PETS have long or short ears? Mental imagery and neuroimaging.

PMID- 7524215
TI  - Axotomy changes peptide expression.

PMID- 7524216
TI  - Common drive of motor units in regulation of muscle force.
AB  - The neuromuscular system is responsible for all our interactions with our
      environment. Although recent decades have witnessed numerous discoveries that
      have shed light into various properties of this system, the basic principles
      underlying its overall operation still remain poorly understood. In this article,
      Carlo J. De Luca and Zeynep Erim discuss the concept of common drive of motor
      units that provides a possible scheme for the control of motor units, unifying
      various seemingly isolated findings that have been reported. According to this
      concept, a pool of motor units that makes up a muscle is controlled collectively
      during a contraction of that muscle. The unique firing patterns of individual
      motor units are effected, not by separate command signals sent to these units,
      but by one common drive to which motor units respond differently. The specific
      architecture of the system and the orderly gradation in the inherent properties
      of individual elements enable a single source to control the activities of all
      the motor units in a given pool. Such an arrangement relieves the CNS from the
      burden of monitoring and regulating each motor unit separately.

PMID- 7524217
TI  - A third parallel visual pathway to primate area V1.
AB  - Recent studies of the primate visual system have focused on the proposal that the
      perception of form and motion are processed by two parallel pathways that
      originate from separate populations of cells in the retina. Earlier proposals for
      parallel processing of visual signals identified a third pathway that could be
      traced from the retina to the visual cortex. This third pathway was assumed to be
      unimportant. A growing body of evidence suggests that this pathway to cortex is
      distinct anatomically, physiologically and neurochemically, and is well
      represented in primates. These findings raise new and interesting questions not
      only about the role of this pathway, but also about the intracortical integration
      of afferent parallel signals.

PMID- 7524219
TI  - Clinical evaluation of trough levels and area under the curve in cyclosporine-
      and FK 506-treated kidney transplant recipients.

PMID- 7524221
TI  - Individual susceptibility to cyclosporine: possible involvement of the CD28/CD80
      (B7/BB1) pathway.

PMID- 7524220
TI  - Antifungal effects of cyclosporine and FK 506 are mediated via immunophilin
      dependent calcineurin inhibition.

PMID- 7524218
TI  - Posttransplant lymphoproliferative disease after heart transplantation on
      Sandimmune therapy: treatment with interferon alfa-2b and intravenous
      immunoglobulin.

PMID- 7524222
TI  - Expression of adhesion molecules in allograft renal dysfunction: a distinct
      diagnostic pattern in rejection and cyclosporine nephrotoxicity.

PMID- 7524223
TI  - Effect of immunosuppressive drugs (CsA, FK 506, rapamycin) on the kidney
      microsomal cytochrome P-450 system in the rat.

PMID- 7524224
TI  - Activation of the renal renin-angiotensin system by cyclosporine A and FK 506 in
      the rat.

PMID- 7524225
TI  - Conversion from CyA to CyA-NOF in a cholestatic liver grafted patient with CyA
      malabsorption.

PMID- 7524227
TI  - [The treatment of prostatic adenoma by local hyperthermia].
AB  - A total of 116 patients aged 51-84 with prostatic adenoma were exposed to local
      hyperthermia (LHT) using "Thermex II" generator (Thechnorex, Israel). The
      analysis of the results involved 4 patient groups: group 1 (34 patients) had
      nycturia > 3 times, residual urine > 50 ml, uroflowmetry index > 8 ml/s; group 2
      (47 patients) had marked symptoms, nycturia < 3 times, residual urine < 50 ml,
      uroflowmetry index 3-7 ml/s; group 3 (2 patients) had cystostomy drainage; group
      4 (2 patients) had acute uresis disorders. The response of the patients was
      registered by subjective complaints, residual urine, uroflowmetry index, pre- and
      after-treatment size of the prostate 1 and 6 months following a session of local
      hyperthermia. A positive effect was achieved in 70% of the patients. LHT proved
      effective in a compensated and subcompensated stages of the disease and in case
      of small-size adenoma nodes.

PMID- 7524226
TI  - FK 506 in solid organ transplantation.

PMID- 7524228
TI  - [1100 transurethral electroresections of prostatic adenomas].

PMID- 7524230
TI  - [Laser treatment of benign prostatic hyperplasia].
AB  - This review article describes the different methods of laser treatment of benign
      prostatic hyperplasia and their development. Published treatment results are
      compared with our own results obtained with different procedures. The aim of
      therapy is to reduce the volume of the gland by coagulation, with subsequent
      secondary ablation or primary vaporization. Due to the desired volume effects Nd:
      YAG lasers are used almost exclusively. The technique most frequently used is
      transurethral laser coagulation of the prostate. Radiation is done in the non
      contact mode with beam-detecting applicators, with either direct vision (VLAP) or
      ultrasound guidance (TULIP). In interstitial laser coagulation of the prostate
      (ILC) laser energy is applied by light guides inserted into the tissue either
      transurethrally or transperineally. Contact lasers are used for incision of the
      prostate or superficial ablation.

PMID- 7524229
TI  - [Poisonous chemicals and urolithiasis].
AB  - For the last 30 years urolithiasis incidence in Kirghizia has been growing. Its
      prevalence is the highest in Chu and Osh rural areas (89%) where farmers widely
      use toxic insecticides. Urban population develop the disease more often (63%),
      especially employees (57.7%) versus workers (27.7%). Urolithiasis occurs in
      workers 8 times more frequently than in farmers. Food products contain
      insecticides in quantities much higher than MAC. The contamination concerns fruit
      and vegetables in a lesser and meat, milk products in greater degrees. In renal
      tissue, blood, urine of urolithiasis patients concentrations of the chemicals
      were increased 4 times against the control samples. In renal tissue and fat of
      urolithiasis animals nephrotoxic insecticides levels surpassed those in the
      controls 2-3 times. Uroliths contain chemicals in great concentrations also.
      Basing on the conformity of geography of insecticides us a ge with urolithiasis
      epidemiological data, high concentrations of the chemicals in food and biological
      objects, frequent occurrence of recurrent urolithiasis in patients known to
      acquire high chemicals levels in renal tissue and urine, it is inferred that
      toxic chemicals are involved in nephrolithiasis genesis by tubular impairment.

PMID- 7524233
TI  - The use of strontium 89 for palliation of pain from bone metastases associated
      with hormone-refractory prostate cancer.

PMID- 7524231
TI  - [Atypical symptoms in patients with germinal testicular tumors].
AB  - The cardinal syndrome of a testicular germ cell tumour is typically scrotal
      enlargement. The present paper compares the group of patients with typical
      scrotal presentation and those who present with atypical symptoms caused by
      metastases. Among 284 retrospectively studied patients, 34 (12%) presented with
      extrascrotal symptoms. The most important were abdominal pain (n = 16) and
      pulmonary symptoms (n = 10). The group of patients with extrascrotal symptoms was
      characterized by the following parameters: percentage of pure seminoma in 35%
      (versus 56% in the patients with typical presentation), elevation of alpha-feto
      protein in 47% (versus 27%), and elevation of beta-HCG in 61% (versus 29%). The
      outcome was lethal in 35% of the patients with atypical presentation, as opposed
      to 6% of those with typical presentation. In 22 patients with extrascrotal
      presenting signs a palpable testicular mass was found on clinical examination.
      Occult testicular tumour proved to be present in 9 patients, and burned-out
      tumours in 3. Unawareness of testicular cancer is a significant factor in
      diagnostic delay. Scrotal palpation should be part of every clinical examination
      in younger male patients with cancer from an unknown primary.

PMID- 7524234
TI  - Morphometry of the prostate: I. Distribution of tissue components in hyperplastic
      glands.
AB  - OBJECTIVES: Morphometry, or quantitative image analysis, offers great promise in
      characterizing the various histologic types of benign prostatic hyperplasia
      (BPH), but to date, a systematic study of the tissue components is lacking. Thus
      we employed morphometry to examine the distribution of primary BPH tissues
      throughout whole human prostates. METHODS: The prostate glands of 20 men with BPH
      were removed for low-volume carcinoma and subjected to a uniform, comprehensive,
      systematic quantification of the primary BPH tissue components using the
      technique of digitization and point-count morphometry. RESULTS: We found the
      following average volumes among the 20 glands: epithelium, 19.9% (S.D. 5.1%,
      range 11.7% to 30.8%); fibromuscular stroma, 50.4% (S.D. 9.4%, range 32.2% to
      74.4%); glandular lumina, 29.7% (S.D. 8.9%, range 11.9% to 47.5%). Within the
      individual prostates, we found symmetry in primary BPH tissue distribution,
      except that the outer prostate was on average 25% richer in epithelium than the
      inner prostate (p < 0.05). When tissue composition was determined in simulated
      biopsy specimens, corrected for radial (ie, inner vs outer gland) orientation,
      the correlation with whole-organ composition was statistically significant for
      "percentage epithelium" (r = 0.72, p < 0.01) and for "stromal/epithelial ratio"
      (r = 0.63, p < 0.01). CONCLUSIONS: Major differences in primary tissue
      composition may separate different hyperplastic prostates. Primary BPH tissues
      are rather symmetrically distributed within individual prostates. Quantitative
      histologic differences between prostates, potentially important in clinical
      decision-making may be accurately diagnosed by morphometry of radially oriented
      biopsy specimens.

PMID- 7524235
TI  - Treatment of benign prostatic hyperplasia by transurethral ultrasound-guided
      laser-induced prostatectomy (TULIP): effects on urodynamic parameters and
      symptoms.
AB  - OBJECTIVES: This prospective study was undertaken to evaluate the effects of
      transurethral ultrasound-guided laser-induced prostatectomy (TULIP) on
      urodynamic, symptomatic, and prostate volume parameters as well as serum prostate
      specific antigen. METHODS: The TULIP procedure was performed in 33 patients with
      benign prostatic hyperplasia with a mean age of 66 years. Patients were evaluated
      by pressure-flow studies, prostate volume measurement by transrectal ultrasound,
      and the American Urological Association (AUA) symptom score. RESULTS: At 3-month
      follow-up, laser prostatectomy has resulted in an increased maximum flow rate
      from 6.6 +/- 0.5 to 11.2 +/- 0.6 mL/s and in an objectively proven relief of the
      urodynamic obstruction, as is evident by a decrease of the average value of the
      urethral resistance parameter URA and the detrusor pressure at maximum flow rate
      from 38.3 +/- 2.7 to 21.3 +/- 1.3 cm water and from 62.7 +/- 4 to 38.9 +/- 2.1 cm
      water, respectively. Symptomatic improvement is evident from a decrease in the
      AUA symptom score from 20.4 at baseline to 8.8 at 6-month follow-up. Although the
      total symptom score did not change significantly between 6 months and 1 year
      follow-up, the score of the symptom "weak stream" was significantly higher again
      at 12 months follow-up. CONCLUSIONS: The TULIP procedure is a urodynamically and
      symptomatically effective treatment. Conclusions about the durability of this
      treatment modality should be made with reservations.

PMID- 7524232
TI  - Prostate cancer kills: strategy to reduce deaths.

PMID- 7524239
TI  - Gene therapy for urologic cancer.

PMID- 7524240
TI  - Production and application of monoclonal antibodies to ovine interleukin-1 alpha
      and interleukin-1 beta.
AB  - Monoclonal antibodies (mAbs) were raised against recombinant ovine interleukin-1
      alpha and beta (ovIL-1 alpha and ovIL-1 beta). Five ovIL-1 alpha specific mAbs
      and three ovIL-1 beta specific mAbs, all of the IgG1 isotype, were characterized.
      Four of the five ovIL-1 alpha specific mAbs, designated 10.36, 10.49, 10.82 and
      5.16, fell into two distinct groups based on several criteria. MAbs 10.36, 10.49
      and 10.82 reacted with recombinant ovIL-1 alpha in Western blot analysis, were
      potent in neutralizing ovIL-1 alpha biological activity in vitro and bound to the
      same or a closely related epitope. MAb 5.16 also bound ovIL-1 alpha in Western
      blot analysis, but was less potent in neutralizing ovIL-1 alpha biological
      activity and bound to a different epitope. A fifth ovIL-1 alpha specific mAb,
      5.01, had some characteristics of antibodies from both groups. While the
      combination of mAb 5.16 with any of 10.36, 10.49 and 10.82 was suitable for
      detection of ovIL-1 alpha in a sandwich immunoassay, the most sensitive detection
      of ovIL-1 alpha utilized mAb 10.82 for capture and a rabbit polyclonal anti-ovIL
      1 alpha antiserum as the detecting antibody in combination with a HRPO-conjugated
      anti-rabbit Ig reagent. This combination of reagents had a detection limit for
      ovIL-1 alpha of 5 pg ml-1 and could detect both recombinant and native ovIL-1
      alpha. Of the three ovIL-1 beta specific mAbs, (designated 2.93, 3.41 and 5.60)
      3.41 and 5.60 recognized the same or a closely related epitope while 2.93
      recognized an epitope more accessible on denatured ovIL-1 beta and proved most
      useful in Western blot analysis. Only mAb 3.41 was potent in neutralizing ovIL-1
      beta biological activity in vitro. A sandwich immunoassay using mAb 3.41 to
      capture ovIL-1 beta and a rabbit polyclonal anti-ovIL-1 beta antiserum as the
      detecting antibody in combination with a HRPO-conjugated anti-rabbit Ig reagent
      had a sensitivity of 5 ng ml-1. The immunoassays were used to assess the relative
      proportions of IL-1 alpha and IL-1 beta in the supernatant of lipopolysaccharide
      stimulated ovine alveolar macrophages with IL-1 beta found to be the predominant
      secreted species of ovIL-1.

PMID- 7524237
TI  - Utility of preoperative serum prostate-specific antigen concentration and biopsy
      Gleason score in predicting risk of pelvic lymph node metastases in prostate
      cancer.
AB  - OBJECTIVES: To determine the accuracy of the preoperative serum concentration of
      prostate-specific antigen (PSA) plus the Gleason pathology score of biopsy
      specimens in predicting the presence of disease in the pelvic lymph nodes in
      patients with prostate cancer. METHODS: The medical records of all patients
      treated for prostate cancer at eight medical centers from January 1988 to June
      1993 were reviewed. There were 932 patients with newly diagnosed prostate cancer
      for whom all relevant data were available who had undergone pelvic
      lymphadenectomy with (n = 912) or without (n = 20) radical prostatectomy. The
      rate of false-negative predictions of metastases based on combined preoperative
      biopsy Gleason score and serum PSA concentration was analyzed. A multivariate
      logistic regression analysis was performed to assess the value of preoperative
      serum PSA and biopsy Gleason scores individually and in combination in predicting
      pelvic lymph node metastases. RESULTS: The false-negative rate of metastases was
      0% for preoperative PSA concentrations < or = 6 ng/mL and biopsy Gleason scores <
      or = 5 (n = 142) and 1.0% for PSA concentrations < or = 10 ng/mL and Gleason
      scores < or = 6 (n = 388). The 95% upper confidence limit for the rate of false
      negativity at this PSA cut-off level was 2.0%. A combination of preoperative
      serum PSA levels and biopsy Gleason scores provided the best prediction for the
      false-negative rates. CONCLUSIONS: For patients with newly diagnosed prostate
      cancer who have biopsy Gleason scores < or = 6 and preoperative PSA
      concentrations < or = 10 ng/mL (42% of our series), a staging pelvic
      lymphadenectomy appears to be unnecessary. The substantial cost associated with
      both cross-sectional imaging and staging lymphadenectomy may therefore be
      avoidable in this group of patients.

PMID- 7524238
TI  - Changes in immunohistochemical staining of PSA, PAP, and TURP-27 following
      irradiation therapy for clinically localized prostate cancer.
AB  - OBJECTIVES: To determine if tissue expression of prostate-specific antigen (PSA),
      prostatic acid phosphatase (PAP), and a prostate-associated monoclonal antibody
      (TURP-27) is retained after irradiation therapy and to compare these results with
      serum levels. METHODS: Immunohistochemical tests were performed on prostatic
      tissue obtained by needle biopsy or transurethral resection prior to and
      following definitive irradiation therapy for clinically localized prostatic
      carcinoma. PSA, PAP, and TURP-27 were studied. Results were compared with serum
      PSA and PAP values. RESULTS: All 20 preirradiation specimens stained positively
      for PSA and PAP; 19 of 20 stained for TURP-27. All 5 of the initial post
      treatment biopsy specimens that showed recurrent tumor stained for all 3 markers.
      In 2 cases, staining for the 3 markers was greatly diminished. Only 8 of 15 post
      treatment biopsy-negative specimens stained for all 3 markers. Six of 15
      demonstrated loss of tissue expression for all 3 antigens. One specimen stained
      for PAP and TURP-27 but failed to stain for PSA. Serum PSA levels paralleled
      tissue expression in recurrent tumor specimens. However, 3 of the post-treatment
      biopsy-positive cases with PAP expressing tissue had normal serum PAP levels.
      CONCLUSIONS: No cases of recurrent tumor with marker-negative tissue were
      identified. However, benign epithelial prostate cells appear to sustain
      sufficient damage from irradiation to lose the capacity to produce certain
      proteins. Diminished contribution of benign glands to circulating PSA, in
      addition to decreased expression in malignant tissues, may explain the lower than
      anticipated serum PSA levels in patients who progress after irradiation therapy.

PMID- 7524241
TI  - HIV-1 TAR RNA has an intrinsic ability to activate interferon-inducible enzymes.
AB  - The TAR sequence at the 5'-termini of all HIV-1 mRNA species forms a stable
      structure that is responsible for both transcriptional and translational
      regulation of HIV-1. Previously we and others reported that purified TAR RNA
      synthesized by in vitro transcription could activate two interferon-induced
      enzymes, the protein kinase (PKR) and 2-5A-synthetase. Because the PKR- and 2-5A
      systems block protein synthesis initiation and induce RNA decay, respectively,
      these findings suggested mechanisms for the control of HIV-1 replication by the
      interferon system. To determine if contaminating dsRNA from in vitro
      transcription reactions was responsible for this effect, as suggested by Gunnery
      et al. 1990, (Proc., Natl. Acad. Sci. USA 87, 8687), we have reexamined these
      findings using chemically synthesized TAR (nucleotides +1 to +57). TAR RNA is
      shown here to have an intrinsic ability to activate PKR and 2-5A-synthetase. In
      contrast, a mutant form of TAR designed to have a disrupted secondary structure
      did not stimulate either enzyme. Chemically synthesized TAR mimicked other dsRNA
      species in its ability to activate and inhibit PKR at low and high RNA
      concentrations, respectively. HIV-1 TAT protein inhibited activation of PKR by
      HIV-1 TAR RNA suggesting an escape mechanism for the virus.

PMID- 7524236
TI  - Comparability of the Tandem-R and IMx assays for the measurement of serum
      prostate-specific antigen.
AB  - OBJECTIVES: To assess the comparability of the Tandem-R and IMx serum prostate
      specific antigen (PSA) assays across levels of the ratio of free-to-total serum
      PSA found in a community-based population of healthy men. METHODS: Banked serum
      samples from the baseline component of the Olmsted County Study of Urinary
      Symptoms and Health Status Among Men were thawed and analyzed using the Tandem-R
      and IMx PSA assays. Serum levels also were determined for the free, noncomplexed
      form of PSA, PSA complexed to alpha-1 antichymotrypsin, and total PSA with a
      research-based immunofluorometric assay. RESULTS: The results of the Tandem-R and
      IMx assays were strongly correlated at all levels of the ratio of free-to-total
      serum PSA. The Spearman correlation coefficients ranged from 0.87 to 0.98 (all p
      < 0.001). The relationship between the Tandem-R and IMx assays, however, differed
      at low levels of free-to-total serum PSA compared with high levels. In the lowest
      10th percentile of the ratio of free-to-total serum PSA (0.04 to 0.18), the IMx
      assay read lower than the Tandem-R (slope +/- standard error = 0.92 +/- 0.04,
      intercept +/- standard error = 0.21 +/- 0.14); whereas in the upper 10th
      percentile of free-to-total ratio (0.46 to 0.65) the IMx assay yielded values
      higher than the Tandem-R assay (slope = 1.21 +/- 0.07, intercept = 0.14 +/-
      0.05). In the middle 90%, the slope did not statistically differ from 1.0.
      CONCLUSIONS: For the majority of men, results of the Tandem-R and IMx PSA assays
      were virtually identical. The small differences found would not be of clinical
      significance for most men but should be considered when comparing results of
      different assays in sequential determinations for a specific man.

PMID- 7524242
TI  - Borna disease virus p24 and p38/40 synthesized in a baculovirus expression
      system: virus protein interactions in insect and mammalian cells.
AB  - To facilitate studies of the individual viral proteins, two Borna disease virus
      proteins, p24 and p38/40, were synthesized in vitro by means of a baculovirus
      expression system and examined for antigenic identity to viral proteins from BDV
      infected cells. Recombinant proteins p24 and p38/40 were nearly identical in size
      to the viral proteins from BDV-infected cells. Immunoblot and immunocytochemistry
      analysis of BDV proteins from infected tissue culture cells and rat brain showed
      binding of antisera directed against the recombinant proteins. Specific
      recognition of the recombinant proteins by Borna disease virus-specific
      convalescent antisera and monoclonal antibodies further demonstrated that the
      antigenic characters of the p24 and p38/40 had been conserved. Polyclonal
      antibody directed against either of the recombinant proteins recognized only the
      protein used as immunogen, without cross reactivity with the other recombinant
      protein, indicating no common epitopes. Moreover, these data confirmed the
      proposed gene coding assignments of ORF I and II of BDV p38/40 and p24,
      respectively. Both of the recombinant proteins were secreted into the media of
      insect cells in tissue culture, but secretion of recombinant p24 was evident only
      as a dimeric form and not with the monomeric form. Immunoprecipitation studies
      performed with monoclonal antibodies and BDV proteins from infected rat brain
      suggested that a heterodimer forms via binding of p40 to the p24.

PMID- 7524244
TI  - Controversy in clinical cancer screening--prostate-specific antigen.

PMID- 7524245
TI  - Multiple marker screening.

PMID- 7524243
TI  - Molecular and cellular aspects of insulin-like growth factor action.

PMID- 7524246
TI  - [Sinus node dysfunction in children without heart defect].
AB  - Sinus node dysfunction (SND) is a rare cause of bradycardia in children without
      structural heart disease. The clinical and diagnostic findings in 4 children with
      this condition are described. Two of them presented with symptoms, in one
      arrhythmias had been noted before birth, and a routine physical examination had
      revealed bradycardia in another. Age at onset of either clinical symptoms or
      bradycardia ranged from 0 to 11 1/2 years. Routine and 24-h-electrocardiograms
      showed atrioventricular junctional rhythms with minimal rates of 25/min and
      episodes of asystole with a maximal duration of 10.3 s. Other
      electrocardiographic abnormalities such as first degree atrioventricular block,
      ventricular extrasystoles or tachycardia were common findings.
      Electrophysiological studies were performed in 3 cases and confirmed the
      diagnosis of SND. A permanent pacemaker was inserted in 2 children; medical
      treatment did not have any long-term effect. During a follow-up period of 5 to 13
      years there were no complications. In summary, SND in childhood can be assessed
      by Holter monitoring with high reliability. Electrophysiological studies are not
      necessary and of limited value. Therapeutic policies and prognostic statements
      are difficult to establish due to the small number of cases so far described.
      Permanent cardiac pacing, however, is unavoidable in symptomatic children.

PMID- 7524247
TI  - The use of random-breakage mapping to locate the genes APN1 and YUH1 in the
      Saccharomyces genome, and to determine gene order near the left end of chromosome
      XI.
AB  - We have used the previously described technique of random-breakage mapping to
      locate the two yeast genes APN1 and YUH1. The APN1 locus is located approximately
      235 kb from the left telomere of chromosome XI, and shows weak (approximately 53
      cM) genetic linkage to ura1. The YUH1 locus is located approximately 140 kb from
      the right telomere of chromosome X, and genetically maps 3.6 cM distal to cdc11.
      In addition, we show by random-breakage mapping that TRP3 is located
      approximately 45 kb from the left telomere of chromosome XI, whereas FAS1 is
      approximately 110 kb from the same telomere. This supports a gene order on the
      left distal portion of chromosome XI that agrees with other physical reports but
      is inverted with respect to Edition 11 of the published genetic map. This report
      confirms that random-breakage mapping is a rapid and convenient method of
      locating cloned genes.

PMID- 7524248
TI  - Transcription regulation of ribosomal protein genes at different growth rates in
      continuous cultures of Kluyveromyces yeasts.
AB  - We have investigated the relationship between the growth rate of two
      Kluyveromyces strains that differ in their maximum growth rate, namely K. lactis
      (mumax = 0.5 h-1) and K. marxianus (mumax = 1.1 h-1), and the transcription rate
      of ribosomal protein (rp) genes in these strains. The growth rate of either
      strain was varied by culturing the cells in a chemostat under conditions of
      glucose limitation at different dilution rates. Although the steady-state levels
      of transcription of the rp-genes of both Kluyveromyces strains were tightly
      coupled to the cellular growth rate, no clear relationship between the level of
      rp-gene transcription and the amount of in vitro binding of the RAP1- and ABF1
      like proteins to the promoters of these rp-genes was observed. Upon a sudden
      increase in the growth rate of a steady-state culture, the transcription of rp
      genes of K. lactis showed a different response from that in K. marxianus. Whereas
      a substantial overexpression of the K. lactis rp-genes was found during at least
      4-5 h, the level of expression of the K. marxianus rp-genes was almost
      immediately adjusted to the new growth rate.

PMID- 7524249
TI  - [Results of surgical therapy of soft tissue sarcoma of the retroperitoneum].
AB  - Between 1.1.1973 and 30.6. 1993 57 patients underwent operation for soft-tissue
      sarcoma of the retroperitoneum. The histological classification showed in 21
      cases a liposarcoma and in 14 cases a leiomyosarcoma. Other histological types
      like fibrosarcoma, malignant fibrous histiocytoma or malignant schwannoma were
      only rarely seen. Complete resection (R-0-resection) was possible in 39 cases
      (73.5%). 6 patients underwent partial resection (R-2-resection) and 8 patients
      had only an explorative laparotomy because of an unresectable tumor. To realize a
      complete resection in 23 cases a multivisceral resection was necessary. The
      postoperative staging according to AJCC showed for 47.7% of the patients a stage
      III- or stage IV- disease. The clinical follow-up was observed between 3 months
      and 14.3 years. The cumulative 5-year-survival-rate for all patients was 38.2%.
      The most important factor for prognosis was the complete resection, while other
      factors like sex and age of patients, size of the tumor and histological type did
      not predict outcome. After complete resection the cumulative 5-year-survival-rate
      was 46.7%, while after partial resection or explorative laparotomy no patient
      survived 5 years.

PMID- 7524252
TI  - [The astrocyte glia of the brain in herpetic encephalitis in children].
AB  - Astrocytic changes were followed up in the brain of infants who had died of
      herpetic encephalitis. Neuro-morphological examinations revealed astrocytic
      structural changes directed to reinforcement of the blood-brain barrier,
      localization of the infection and, possibly, to inactivation of the virus.

PMID- 7524253
TI  - [Rochalimaea henselae, Afipia felis and cat-scratch disease].
AB  - Several years ago, Rochalimaea henselae has emerged as an agent of bacillary
      angiomatosis, bacillary peliosis and recurrent septicaemia that generally occur
      in patients infected with human immunodeficiency virus. An aetiologic role in cat
      scratch disease is also suspected widely on the basis of a serologic survey. Its
      slow growth and its culture requirement explain that this pathogen, a gram
      negative bacterium, could not be isolated until 1990. Moreover, blood and tissue
      samples request lysis and crushing for recovering by culture. The clinical,
      histological, microbiological and pathogenic aspects of these infections are
      described and discussed.

PMID- 7524251
TI  - [The effect of staphylococcal peptidoglycan on macrophage interferon formation
      and bactericidal activity].
AB  - Staphylococcus aureus cell-wall peptidoglycan has been shown to stimulate the
      bactericidal activity of peritoneal exudate macrophages. A more pronounced
      activating effect of peptidoglycan on the bactericidal activity of macrophages
      has been detected in the stimulated test. Peptidoglycan in doses of 5-100 mg
      induced interferon production by intact mouse splenocytes after 24-hour
      exposition with it. Peptidoglycan has been found to produce the most intensive
      effect on interferon production when injected intraperitoneally in a dose of 100
      mg after 4-hour exposition.

PMID- 7524254
TI  - Joys and sorrows of a palliative care volunteer: a personal perspective.

PMID- 7524250
TI  - [The immunodiagnosis of melioidosis by a solid-phase variant of
      radioimmunological analysis (RIA)].
AB  - A variant of the solid-phase radioimmunoassay (RIA) has been developed for the
      detection of specific immunoglobulins in laboratory animals infected with
      Pseudomonas pseudomallei. The proposed method has advantages over the indirect
      hemagglutination test and the enzyme immunoassay in its sensitivity and
      specificity. The newly developed RIA variant, based on group-specific antigens 6
      + d, makes it possible to classify the strain causing the disease with the Asian
      or Australian serovar of P. pseudomallei according to the composition of detected
      immunoglobulins.

PMID- 7524256
TI  - Cardiovascular effects of moderate normovolaemic haemodilution during enflurane
      nitrous oxide anaesthesia in man.
AB  - The cardiovascular effects of mild normovolaemic haemodilution during enflurane
      nitrous oxide anaesthesia were studied in 20 patients with normal cardiac
      function before, during and after total hip replacement. After induction of
      anaesthesia, patients were randomly allocated to one control group (C), or one
      haemodiluted group (H) where Hct was decreased to 30% by replacement of blood
      volume by an identical volume of hydroxyethyl starch 200/05. Each patient was
      monitored with a pulmonary artery catheter allowing the measurement of right
      ventricular ejection fraction. During haemodilution, stroke index and right
      ventricular end-diastolic volume index increased from 33.1 +/- 7.9 to 39.3 +/-
      7.1 ml.M-2 and from 73.8 +/- 20.3 to 94.9 +/- 18.5 ml.M-2 respectively (mean +/-
      s.d., both P < 0.05). However, heart rate decreased so that cardiac index did not
      change. O2 delivery decreased significantly (from 389 +/- 70 to 311 +/- 63 ml.min
      1.m-2; P < 0.05), but was not different to the control group. O2 consumption was
      maintained by an increase in O2 extraction. During the surgical procedure,
      cardiac index was higher in the haemodiluted group than in the control group, so
      that O2 delivery was similar in the two groups. O2 consumption tended to be
      greater in the haemodiluted group. In patients with normal cardiac function,
      enflurane-nitrous oxide anesthesia could alter the normal physiologic response to
      mild normovolaemic haemodilution.

PMID- 7524255
TI  - Influence of volume replacement with different HES-solutions on microcirculatory
      blood flow in cardiac surgery.
AB  - A variety of hydroxyethyl starch HES preparations with different molecular weight
      average (Mw) and molar substitution (MS) is available for volume replacement
      during acute normovolemic haemodilution (ANH). Particularly with regard to
      microcirculation, the ideal solution for volume therapy has not been found. The
      influence of four different HES preparations on macro- and microcirculation was
      investigated in 40 patients scheduled for elective aorto-coronary bypass grafting
      and undergoing ANH (preoperative withdrawn blood: 10 ml.kg-1): 1) 6% HES with Mw
      of 450,000 dalton and MS of 0.7; 2) 6% HES with Mw of 200,000 dalton and MS of
      0.5; 3) 6% HES with Mw of 200,000 dalton and MS of 0.62; 4) 6% HES with Mw of
      40,000 dalton and MS of 0.5. A 5th group without ANH served as a control (10
      patients in each group). In addition to systemic haemodynamics and various
      laboratory parameters, skin capillary blood flow was measured by laser Doppler
      flowmetry. Laser Doppler flow (LDF) was monitored simultaneously at the patient's
      forehead and forearm. Changes in systemic haemodynamics were similar in all ANH
      patients. Systemic vascular resistance (SVR) was lowest after infusion of HES
      200/0.5. The most pronounced increase in plasma viscosity was in patients of
      group 1 (450/0.7) (P < 0.05) and plasma viscosity remained highest during the
      entire investigation period in these patients. After ANH, skin capillary blood
      flow measured at the forehead decreased in all patients except in patients of
      group 2 (200/0.5: max. +18%). Group 3 (200/0.62) showed the highest decrease in
      forehead-LDF. During CPB, forehead-LDF decreased significantly in groups 3
      (200/0.62) and 4 (40/0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524257
TI  - The contractile response of thiopental in large and small ovine airways.
AB  - The present study addresses the question of bronchial reactivity towards
      thiopental using pharmacological assay and ultrastructural analysis with
      transmission electron-microscopy in sheep airways. Smooth muscle strips of the
      upper, middle and lower trachea and small size bronchial rings of sheep were
      investigated using organ bath technique with monitoring of isometric tension in
      response to thiopental (10(-7)-10(-4)M), histamine (10(-4)M) and carbachol (10(
      8)M). Thiopental elicited contractile responses in the large airways, with most
      marked contractions in the upper trachea. In the small lobar bronchi thiopental
      caused a biphasic response with predominant relaxation. Similar reactions could
      be elicited by histamine. Ultrastructural studies showed a large number of mast
      cells with equal distribution throughout the bronchial tree. Histamine release
      from bronchial tissue was detected by bioassay after thiopental challenge. It can
      be concluded that thiopental at a concentration of 10(-4)M releases histamine
      from mast cells within the airways with consequent constriction in the trachea
      and mainly dilatation in the smaller intralobular airways. Under these conditions
      therefore, one does not necessarily expect a net change of airflow resistance
      with thiopental anaesthesia.

PMID- 7524258
TI  - Optic neuritis and multiple sclerosis: the T cell repertoires to myelin proteins
      and MBP peptides change with time.
AB  - Autoreactive T cells recognizing myelin basic protein (MBP), proteolipid protein
      (PLP) and MBP peptides have been described in multiple sclerosis (MS) and optic
      neuritis (ON), but their role in disease pathogenesis, if any, is unknown. A
      consistency of the T cell repertoire over the course of MS and ON should
      facilitate the development of specific immunotherapies. We have examined the T
      cell responses to autoantigens in two consecutive blood specimens taken from
      patients with ON and MS, and in two consecutive CSF specimens obtained from ON
      patients. As read-out numbers of T cells responding to antigen stimulation by the
      secretion of interferon-gamma were estimated. Pronounced differences in
      occurrence and numbers of T cells recognizing MBP, MBP peptides with the amino
      acid sequences 63-88, 110-128 and 148-165, and PLP were noticed in individual ON
      and MS patients over the course of disease. The MBP peptide among those three
      included, that was predominantly recognized by T cells in the individual patient,
      also varied over the course. The quantitative and qualitative changes of the
      myelin antigen-specific T cell response in MS and in ON, the latter to a certain
      extent reflecting the situation in early MS, do not favor the future useful
      development of specific immunotherapies in these diseases.

PMID- 7524265
TI  - Increased granulocyte-colony stimulating factor (G-CSF) levels in neonates with
      perinatal complications.
AB  - We have investigated cord blood granulocyte-colony stimulating factor (G-CSF)
      levels in neonates with or without neonatal complications to examine some changes
      in the G-CSF levels in the neonatal period. The G-CSF levels were measured in 613
      neonates by enzyme immunoassay. The results showed that G-CSF levels were
      distributed in a broad range from the level under the cutting point (31 pg/mL) to
      over the measurable range (2000 pg/mL). Normal neonates without perinatal
      complications were 322. In normal neonates, the G-CSF level correlated with the
      gestational age (r = 0.255, P < 0.01) and cord blood leukocyte count (r = 0.210,
      P < 0.01). The G-CSF values were under 100 pg/mL in 95% of normal neonates with a
      median of 35.0 pg/mL. We divided the neonates into two groups: a lower (< 100
      pg/mL) and a higher (> or = 100 pg/mL), based on the G-CSF level. The percentage
      of neonates with higher G-CSF levels (> or = 100 pg/mL) was greater in neonates
      with perinatal complications than in normal neonates (< 100 pg/mL; P < 0.01).
      Compared with normal neonates, the percentages of the higher group were greater
      in neonates with infections (P < 0.01), fetal distress (P < 0.01), premature
      rupture of membranes (P < 0.05), neonatal asphyxia (P < 0.01) and meconium
      staining of amniotic fluid (P < 0.01). Neonates with higher G-CSF levels had
      larger numbers of peripheral leukocytes (P < 0.05) than did those with the lower
      G-CSF levels. Counts of leukocytes were parallel with those of
      neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524259
TI  - Th1-like cell responses to peripheral nerve myelin components over the course of
      experimental allergic neuritis in Lewis rats.
AB  - Experimental allergic neuritis (EAN) is a T cell-mediated animal model of
      Guillain-Barre syndrome characterized by inflammation and demyelination of
      peripheral nerves. EAN can be induced by immunization of rats with bovine
      peripheral nerve myelin (BPM) or the myelin proteins P2 or P0, but the extent of
      T cell responses over the course of EAN is incompletely defined. We studied the T
      cell responses to these proteins and the glycolipid GM1 by enumerating T helper
      type 1 (Th1)-like cells secreting interferon-gamma (IFN-gamma) after short-term
      culture of mononuclear cells (MNC) in presence of antigen. Already 7 days post
      immunization (p.i.) with BPM and before onset of clinical EAN, lymph nodes
      contained elevated levels of P2 responsive T cells. At the height of EAN on day
      14 p.i. and during recovery, T cell levels responding to BPM, P0 and GM1 were
      also elevated. The same temporal profiles and specificities were registered for
      antigen reactive spleen MNC. The results implicate that Th1-like cells with
      multiple specificities including the glycolipid GM1 occur at increased levels in
      lymphoid organs in EAN rats, and that IFN-gamma may be an important effector
      molecule in the induction of nerve damage.

PMID- 7524260
TI  - S-adenosylmethionine levels in psychiatric and neurological disorders: a review.
AB  - INTRODUCTION: S-adenosylmethionine (SAMe) is an important methyl donor in over 35
      methylation reactions involving DNA, proteins, phospholipids and catechol- and
      indole- amines. MATERIAL AND METHODS: This article reviews the studies that have
      examined brain and blood levels of SAMe in several psychological, neurological
      and metabolic disorders. RESULTS: Although studies have found no consistent
      changes in whole blood SAMe levels in psychiatric patients, other investigators
      have found low cerebrospinal fluid (CSF) SAMe levels in patients with
      neurological disorders such as Alzheimer's dementia, subacute combined
      degeneration of the spinal cord (SACD), and HIV-related neuropathies, as well as
      in patients with metabolic disorders such as 5, 10-CH2-H4 folate reductase
      deficiency. CONCLUSION: Intravenous or oral administration of SAMe thus
      represents a possible treatment for these neurological and metabolic disorders.

PMID- 7524264
TI  - Aberrant distribution of tyrosine hydroxylase and substance P in infants with
      brain-stem infarction.
AB  - The distribution of tyrosine hydroxylase (TH) and substance P (SP) was examined
      in the brain-stem of 4 infants with respiratory abnormalities associated with
      remote brain-stem or cerebellar infarction utilizing immunohistochemical methods.
      TH-immunoreactive cells and SP-immunoreactive fibers were found in and around the
      area of the infarction in the tegmentum, in amounts and sites different from that
      seen in controls. The aberrant localization of SP and TH may represent an altered
      repair process associated with resolution of the infarction and may be related to
      abnormal respiratory control or sudden death.

PMID- 7524263
TI  - A multicenter, randomized, controlled trial of intravenous gamma globulin therapy
      in children with acute Kawasaki disease.
AB  - We studied the effect of intravenous, polyethyleneglycol-treated, human
      immunoglobulin, administered at 200 mg/kg per day (group A: n = 147; male 86,
      female 61; age < 1 year, 50) or 400 mg/kg per day (group B: n = 152; male 87,
      female 65; age < 1 year, 52) for five consecutive days and compared it with
      freeze-dried, sulfonated human immunoglobulin [group C: n = 152; male 87, female
      65; age < 1 year, 51), administered at 200 mg/kg per day for five consecutive
      days, on the prevention of coronary artery abnormalities in Kawasaki disease.
      Echocardiograms were interpreted blindly and independently. Proportions of 87.1%,
      95.4%, and 82.3% in groups A, B, and C, respectively, had no coronary artery
      abnormalities. The confidence limits of difference between the proportions of
      groups A and C, groups B and C, and groups B and A were -4.4% and 10.4%, 7.8% and
      15.9%, and 4.0% and 10.8%, respectively. Duration of fever and serum
      immunoglobulin G (IgG) levels were correlated with the prevalence of coronary
      artery abnormalities. We concluded that intravenous, polyethyleneglycol-treated,
      human immunoglobulin and freeze-dried, sulfonated human immunoglobulin had
      clinically equivalent effects on coronary artery abnormalities, and that five
      daily doses of 400 mg/kg of intravenous, polyethyleneglycol-treated, human
      immunoglobulin is more effective than that of 200 mg/kg gamma globulin.

PMID- 7524261
TI  - Characterization of a shared epitope in cortical Lewy body fibrils and Alzheimer
      paired helical filaments.
AB  - The straight fibrils of the Lewy body contain an epitope related to
      phosphorylation of the KSPV motif common to the C termini of the 200- and 170-kDa
      neurofilament subunits and tau. To further characterize this phosphorylated
      neurofilament/tau epitope in Lewy bodies and to analyze the constituents of
      isolated Lewy bodies we used a combined biochemical and immunochemical approach.
      In formalin-fixed paraffin-embedded tissue cortical Lewy bodies were labelled by
      monoclonal antibodies directed to phosphorylation-dependent KSPV epitopes in the
      sequences of neurofilament and phosphorylation-independent epitopes.
      Immunoblotting of solubilized Lewy body fibrils with the same antibodies which
      stained Lewy bodies in tissue sections revealed that the immunoreactive Lewy body
      proteins were phosphorylated neurofilament subunits. An antibody to the 68-kDa
      neurofilament subunit labelled Lewy bodies and Lewy body protein at 50-68 kDa. We
      conclude that the shared phosphorylated epitope in Lewy body fibrils and paired
      helical filaments is related to the common KSPV sequence in neurofilament and
      tau, and that all three neurofilament subunits are present in the Lewy body. This
      result indicates that although Lewy bodies and neurofibrillary tangles share
      epitopes they are comprised of distinct structural subunits.

PMID- 7524266
TI  - Importance of recall and follow-up screening for chronic hepatitis C in children
      receiving blood products prior to 1990 in Japan.
AB  - The objective was to detect chronic hepatitis C virus infection in recipients of
      blood products using retrospective analysis by recall and enrollment of
      recipients. 226 patients who received blood products for open heart surgery from
      January 1983 to June 1992 were examined for HCV antibody by using a second
      generation assay and liver function test. 22 (14%) of the 161 patients who
      received blood products before November 1989 had detectable HCV antibody, but
      none of the 65 recipients receiving blood products after 1990, the year the
      Japanese blood bank began to screen for HCV-antibody. Abnormal alanine
      aminotransferase (ALT) levels, more than 25 iu/L, during the chronic phase of HCV
      infection was recognized in nine of 22 (41%) seropositive patients. The liver
      function test and second generation HCV antibody in the serum are effective
      markers to screen for chronic hepatitis C in blood product recipients transfused
      before 1990.

PMID- 7524262
TI  - Increased expression of phosphotyrosine after axotomy in the dorsal motor nucleus
      of the vagus nerve and the hypoglossal nucleus.
AB  - To investigate the role of tyrosine kinase underlying glial cell proliferation
      after axotomy, the localization of phosphotyrosine was studied
      immunohistochemically in the dorsal motor nucleus of the vagus nerve and the
      hypoglossal nucleus after nerve transection in adult rats. An anti
      phosphotyrosine antibody weakly stained the cytoplasm of the neurons and some
      glial cells on the control side of both nuclei, while preferentially staining the
      plasma membrane of perineuronal microglial cells and neurons weakly on the
      severed side 2 days after axotomy and intensely between 3 and 7 days. Some of the
      microglial cells reacted positively with both anti-bromodeoxyuridine and anti
      phosphotyrosine antibodies, suggesting that tyrosine kinase is involved in
      microglial cell proliferation. Proliferation of numerous microglial cells was
      observed in the severed nuclei between 2 and 4 days after axotomy, while only a
      few were detected on days 5 and 7. These findings suggest that tyrosine kinase is
      involved in not only the proliferation of perineuronal microglial cells but also
      in some retrograde neuronal reactions such as differentiation and regeneration.

PMID- 7524267
TI  - Non-adrenergic, non-cholinergic vascular control with reference to neuropeptide
      Y, vasoactive intestinal polypeptide and nitric oxide.
AB  - 1. NOS-immunoreactivity was shown to be colocalized with vasoactive peptides such
      as VIP, PHI and NPY in postganglionic parasympathetic neurons to the
      submandibular gland. NOS-immunoreactivity was on the other hand found in
      preganglionic neurons in sympathetic ganglia but only in few postganglionic
      sympathetic neurons. These latter neurons also contained VIP and PHI. NPY was
      present in postganglionic perivascular sympathetic nerves in all organs studied.
      2. Large vasoconstrictor responses were evoked by sympathetic nerve stimulation
      in the pig and dog after depletion of NA by reserpine treatment combined with
      interruption of nerve activity. Reserpine resistant vascular responses were
      obtained already at single pulse stimulation in pig skeletal muscle but the
      sensitivity to nerve stimulation varied with type of vascular bed. In general,
      the maximal vasoconstriction obtained after reserpine treatment was smaller than
      in controls but the duration of the response was prolonged. 3. In control
      condition NPY overflow was relatively well maintained. The severalfold larger NPY
      overflow obtained after reserpine treatment compared to control conditions
      contributes to the gradual peptide depletion upon repeated stimulation and is
      likely to be related to lack of prejunctional alpha 2-adrenoceptor inhibition of
      transmitter release. NPY also regulated transmitter release via a prejunctional
      action. The NPY-LI in splenic venous effluent upon sympathetic stimulation after
      reserpine reached levels where exogenous NPY causes vasoconstriction. 4. NPY and
      NPY analogues caused long-lasting vasoconstriction. The dominating vascular NPY
      receptor seemed to be of the Y1 type, which mediated vasoconstriction in all
      vascular beds investigated and also increased MABP. A population of
      postjunctional Y2 receptors was also present in the splenic vascular bed in
      addition to its prejunctional localization on sympathetic nerves. 5. Inhibition
      of NO production by L-NNA caused general vasoconstriction, reduction in cardiac
      output and increase in MABP. L-NNA caused larger vasoconstriction in intact than
      in sympathetically denervated hind limb. After inhibition of NO production,
      preganglionic sympathetic nerve stimulation of the hind limb and nasal mucosa had
      vasoconstrictor effects only slightly different from those seen in control
      conditions. Both the cholinergic and non-cholinergic components of the
      parasympathetic nerve-mediated vasodilatation in the submandibular salivary gland
      were on the other hand markedly suppressed by L-NNA. 6. VIP- and ACh-evoked
      vasodilatory effects in the submandibular salivary gland were reduced after NOS
      inhibition. Also the overflow of NPY-LI evoked by parasympathetic nerve
      stimulation of the submandibular salivary gland was suppressed by L-NNA.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7524268
TI  - Changes in plasma concentrations of vitronectin in patients with diabetic
      nephropathy.
AB  - To investigate the role of vitronectin in the progression of diabetic
      nephropathy, plasma concentrations of vitronectin were measured by enzyme-linked
      immunosorbent assay in patients with diabetes mellitus and compared with normal
      control subjects. In diabetic patients with normoalbuminuria and
      microalbuminuria, plasma concentrations of vitronectin were significantly higher
      than those of control subjects. Plasma concentrations of vitronectin in diabetic
      patients with chronic renal failure were significantly lower than those with
      normal renal function. There was a significant positive correlation between
      plasma concentration of vitronectin and blood platelet counts. In the early stage
      of diabetic nephropathy, vitronectin may be increased caused by synthesis from
      activated platelets. With progression of diabetic nephropathy, plasma vitronectin
      may be decreased because of accumulation in sclerotic glomeruli and
      arteriosclerotic lesions. In conclusion, the plasma concentration of vitronectin
      appears to be an important marker for the progression of diabetic nephropathy.

PMID- 7524269
TI  - Quantitation of hepatitis C virus RNA in liver tissue as a predictive marker of
      the response to interferon therapy in chronic hepatitis C.
AB  - Recently, factors predicting the response to interferon (IFN) therapy against
      hepatitis C virus (HCV) have received much attention. To evaluate the usefulness
      of the quantitation of intrahepatic HCV RNA as a predictive marker of the
      response to IFN therapy, we compared the amount of intrahepatic HCV RNA with
      serum levels in 16 patients. Eleven patients who had 10(10) copies/g or more of
      intrahepatic HCV RNA had increased level of serum alanine aminotransferase (ALT)
      after IFN therapy, while 4 of 5 patients who had less than 10(10) copies/g of
      intrahepatic HCV RNA achieved sustained normalization of serum ALT level and were
      designated as complete responders. Four complete responders possessed
      significantly less HCV RNA in the liver parenchyma than partial and nonresponders
      (P = 0.010, Mann-Whitney U-test), but the amount of HCV RNA in the serum was not
      significantly different between those groups. In conclusion, the results suggest
      that the quantitation of intrahepatic HCV RNA is a better indicator of the
      response to IFN therapy than serum HCV RNA.

PMID- 7524270
TI  - Acute effects of perinatal hypoxic insult on concentrations of dopamine,
      serotonin, and metabolites in fetal monkey brain.
AB  - Seven monkeys (Macaca mulatta) were laparotomized under general anesthesia
      (halothane, nitrous oxide, oxygen). Fetal hypoxia was induced in four monkeys by
      occlusion of the umbilical cord with a hydraulic occluder for 5-6 min. Three sham
      operated fetuses served as controls. After unclamping, the fetuses were allowed
      to reperfuse for 20-30 min. To monitor hypoxia, the fetal electrocardiogram was
      recorded continuously. Hypoxic insult was associated with a decrease in fetal
      heart rate during the occlusion. After reperfusion, fetuses were immediately
      sacrificed and neocortex regions dissected on ice, frozen on dry ice and stored
      at -70 degrees C. Dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid,
      serotonin, and 5-hydroxyindoleacetic acid were assayed by high performance liquid
      chromatography with electrochemical detection (HPLC/EC) in hippocampus, caudate
      nucleus and cortical regions. In the hippocampus, there was a significant
      increase in 5-hydroxyindoleacetic acid concentration. In prefrontal cortex, there
      was a trend toward an increase in serotonin but no effects on dopamine and
      homovanillic acid concentrations. Dopamine, serotonin and metabolites were not
      altered in the caudate nucleus. These data demonstrate that fetal hypoxia
      followed by reperfusion produced an increase in serotonin concentration measured
      within the hippocampus and selected cortical areas known to be targets of hypoxic
      injury.

PMID- 7524271
TI  - Maturational changes in sympathetic and sensory innervation of the rat uterus:
      effects of neonatal capsaicin treatment.
AB  - The plasticity of the sympathetic and sensory innervation of the rat uterus was
      examined, before and after puberty, in controls and in animals where primary
      sensory nerves had been destroyed by neonatal capsaicin treatment.
      Immunohistochemical and histochemical methods were used in association with nerve
      density measurements and biochemical assays. The main findings were as follows:
      (1) Puberty was associated with a marked increase in the weight of the uterine
      horn, uterine cervix and parametrial tissue. This was unaffected by capsaicin
      treatment. (2) The sympathetic innervation of the uterine horn and parametrial
      tissue was reduced following puberty as revealed by a decrease in the density of
      noradrenaline-containing nerves and a marked decrease in the tissue concentration
      of noradrenaline. Sympathetic nerves supplying the uterine cervix and the blood
      vessels of the uterus appeared to be unaffected by puberty. (3) In contrast, the
      sensory supply of the uterus by substance P and calcitonin gene-related peptide
      containing nerves increased in parallel with uterine growth during puberty
      resulting in no change in nerve density and only a slight reduction in peptide
      concentration. (4) Neonatal capsaicin treatment caused a long-lasting depletion
      of substance P- and calcitonin gene-related peptide-containing nerves. In the
      uterine horn and parametrial tissue, capsaicin-resistant calcitonin gene-related
      peptide, but not substance P, still increased with tissue weight during puberty,
      indeed, in the uterine horn, the relative increase was greater than in controls.
      (5) Sensory denervation resulted in an increase in the non-vascular sympathetic
      supply of the uterus, although there was a regional variation in the time course
      of the response. Perivascular sympathetic nerves were unaffected by capsaicin
      treatment. The pattern of change in non-vascular noradrenaline-containing nerves
      associated with puberty was similar in nature to controls. Thus, there is
      considerable plasticity in the innervation of the uterus both during puberty and
      following sensory denervation. A complex pattern of change occurs with
      differential responses in vascular and nonvascular nerves and in different
      regions of the uterus. Such differences may be due in part to the different
      origins of individual nerve populations and/or to their relative sensitivities to
      sex hormones.

PMID- 7524273
TI  - Substance P (SP) and neurokinin A (NKA) in developing submandibular glands of the
      rat.
AB  - The effect of isoprenaline, carbachol, substance P (SP) and neurokinin A (NKA) on
      peroxidase and total protein secretion was studied in the developing postnatal
      submandibular glands of the rat using in vitro methods. Submandibular glands of
      1, 5, 12 and 30 day-old rats were stimulated by 10(-5) M isoprenaline and
      carbachol, and 10(-6) M SP and NKA. The stimulatory effects of these compounds
      were compared to the basic release of peroxidase and total amount of protein from
      submandibular gland fragments in incubation solution with no added transmitter
      substances. Indirect immunohistochemical methods were used to study these
      developing glands from SP- and NKA-immunoreactive (IR) nerve fibers. The
      distributions of SP-IR and NKA-IR nerve fibers closely resembled each other,
      being most abundantly spread around the developing acini and ducts. The number of
      these fibers was high on the 1st, 5th and 12th days, but was decreased on the
      30th day. On peroxidase release, isoprenaline was the most effective, causing a
      maximal response of 47 times the basic release on the first postnatal day, after
      which it gradually decreased. The effects of carbachol, SP and NKA on peroxidase
      release were clearly weaker and, unlike isoprenaline, their strongest response
      was on the 5th postnatal day (carbachol, 4.3; SP 5.2; NKA, 4.5). The total
      protein secretion effect patterns of the studied substances resembled each other
      more, showing their strongest response on the 5th day (isoprenaline, 5.0;
      carbachol, 4.5; SP, 4.2; NKA, 3.4) and decreasing thereafter.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7524272
TI  - Neuronal phenotypes in mouse dorsal root ganglion cell cultures: enrichment of
      substance P and calbindin D-28k expressing neurons in a defined medium.
AB  - The primary sensory neurons in mouse dorsal root ganglia consist of diversified
      subpopulations which express distinct phenotypic characteristics such as
      substance P or calbindin D-28k. To determine whether neuronal phenotypes are
      altered or not in in vitro cultures carried out in a defined synthetic medium,
      dissociated dorsal root ganglion cells from newborn mice were grown in the alpha
      modified minimum essential medium either supplemented with 10% fetal calf serum
      or serum-free. About 80% of the neurons survived after 5 days of culture in both
      media, but only 35% or 65% were rescued after 12 days in serum-free or fetal calf
      serum supplemented medium, respectively. The neuronal subpopulations expressing
      substance P or calbindin D-28k displayed similar morphological properties in both
      media and a higher resistance to culture conditions than the whole neuronal cell
      population, especially in serum-free medium. It is therefore concluded that a
      defined synthetic medium offers reproducible conditions to culture dorsal root
      ganglion cells for at least 5 days, stimulates the expression of substance P and
      enriches preferentially neuronal phenotypes expressing substance P or calbindin D
      28k, for a longer period of culture.

PMID- 7524274
TI  - Presynaptic ecto- and postsynaptic endo-calcium-adenosine-triphosphatases in
      synaptosomes: doubts about biochemical interpretation of localization.
AB  - Ecto- and endo-Ca-adenosine-triphosphatase (ATPase) activity was identified as
      electron-dense lead or cerium phosphate precipitate in the rat cortical
      synaptosomes by transmission electron microscopy and enzyme histochemistry. The
      formation of the deposit was dependent on the presence of ATP (the substrate), Ca
      (activator) and levamisole, quercetin or ouabain (inhibitors of different
      phosphatases and ATPases). Reaction products were found at the external surface
      of the presynaptic membrane, both surfaces of the postsynaptic membrane, in the
      synaptic cleft and in the free mitochondrial membranes. In the presence of ATP
      and the three inhibitors together, the quantity of the precipitate decreased
      markedly, but we still found some deposit on the external surface of the
      presynaptic membrane (this activity is probably due to the so-called ecto-ATPase)
      and on the internal surface of the postsynaptic one (endo-ATPase). The
      distinction between ecto- and endo-ATPases in biochemical fractions solely upon
      biochemical differential measurements must be interpreted with caution.

PMID- 7524276
TI  - Preventive effect of intracisternal heparin for proliferative angiopathy after
      experimental subarachnoid haemorrhage in rats.
AB  - Proliferative angiopathy represents the morphological basis of delayed cerebral
      vasospasm. The initial vasoconstriction and endothelial damage of the vasospastic
      arteries leads to an exaggerated response of the smooth muscle cells within the
      media leading to subintimal thickening and myonecrosis. Heparin reduces the
      exposure of the media to platelet derived growth factor, a mitogen from
      aggregating platelets responsible for the migration and proliferation of the
      myofibroblasts. Since systemic heparin in the setting of a subarachnoid
      haemorrhage would be unacceptable, we have tested the effect of heparin on
      proliferative angiopathy by injecting autologous non-heparinized blood into two
      groups of rats (N = 12 each) and then inject the heparin into the spinal fluid of
      one group after one hour. We were able to show histologically that intracisternal
      heparin injection after the subarachnoid haemorrhage has reduced the vascular
      wall changes to a great degree. Heparinization of the cerebrospinal fluid carried
      out in conjunction with early operation for aneurysms may be a promising approach
      to prevent the morbid complications of SAH in the clinical setting.

PMID- 7524275
TI  - Effect of subarachnoid haemorrhage on trigeminovascular calcitonin-gene-related
      peptide and substance P of the rat dura mater versus cerebral vasculature.
AB  - While the presence of a robust perivascular neural network accompanying cerebral
      and dural blood vessels that contain various neuropeptides is well documented,
      the functional significance of this innervation is unclear. Following
      experimentally induced subarachnoid haemorrhage (SAH) in animal models,
      immunocytochemical studies have revealed that changes occur in the staining
      intensity of some of these neuropeptides. This study compared the immunostaining
      intensity of calcitonin-gene-related peptide (CGRP) and substance P (SP) in
      cerebral and dural perivascular nerve fibers after SAH in the rat. Subarachnoid
      haemorrhage was produced by injecting 0.3 ml of autologous blood into the
      cisterna magna of male Sprague Dawley rats. Sham operated animals received an
      equal volume of buffered lactated Ringer's solution (pH 7.4). Changes in the
      immunostaining intensity of cerebral and dural vessels were evaluated by
      independent observers at 6, 24, and 48 hours after SAH. Immunostaining of CGRP
      was reduced in cerebral vessels at 6 hours and returned to normal by 48 hours. In
      contrast, CGRP immunostaining of dural perivascular nerve fibers was unchanged at
      all time periods examined. A marked decrease in SP immunostaining was documented
      at 6 hours in both the cerebral and dural vessels in all animals; at 48 hours,
      the staining intensity had returned to control levels. These results support the
      idea that several subpopulations of trigeminovascular neurons containing CGRP,
      SP, or both project to cerebral and dural vessels. Since these subpopulations may
      be differentially activated in pathologic conditions, such as SAH or vascular
      headache, the potential exists for pharmacologic intervention of specific
      neuropeptides with the resultant abatement of a pathologic process.

PMID- 7524280
TI  - [Clinico-flowmetric analysis of patients being surgically treated for BPH].
AB  - Benign prostatic hypertrophy (BPH) is a common urological disease with a standard
      surgical approach, transurethral resection (TUR) or open adenectomy (OA), but the
      flowmetric clinical results are controversial. Fifty-five patients were
      evaluated; in 23 of them TUR was performed and 32 underwent OA. The Boyarsky
      clinical questionnaire was filled in, and a flow evaluation conducted prior and
      subsequent to the procedure to measure maximum and average flow (Qmax and Qave)
      which was correlated to mictional volume according to Siroky's nomogram. The
      purpose is to compare the flowmetric clinical results of TUR and OA, and to
      evaluate flowmetry as a prognostic factor. Correlation of obstructive symptoms
      and Qmax is low (r = 0.49) and minor for irritative symptoms. Both groups of
      patients achieve significant clinical improvement (p < 0.001). OA obtains a 248%
      increase in Qmax, while this figure is 76% with TUR. Patients with post-treatment
      obstruction after OA are 9.3%, and 26.9% for TUR. Results are better when Qmax
      prior to surgery is < 5 ml/s than when it is > 10 ml/s.

PMID- 7524277
TI  - [Correlation between bone gammagraphy and biochemical parameters in bone turnover
      in patients with prostate cancer].
AB  - Evaluation of osteocalcin (BGP), hydroxyproline/creatinine (HxP/Cr) and PSA
      values in 43 patients with prostate cancer, 25 with spread disease (bone
      metastasis) and 18 with no bone dissemination. Correlation of values obtained
      with the patient's clinical status: complete response, partial response, steady
      state and progression. Mann-Whitney's U test shows statistical significance (P <
      0.001) when patient's PSA values are compared to non-disseminated disease with
      regard to those with bone metastasis, the same result being obtained with the
      HxP/Cr ratio. Comparison of BGP figures within the same groups did not reach
      statistical significance, although the number of patients with abnormally high
      BGP values was considered to be much higher in patients with disseminated (52%)
      versus non-disseminated (11%) condition. We conclude that both a deeper knowledge
      of bone dynamics in these patients and, therefore, evolutive follow-up of bone
      turnout and resorption is required in order to establish clinically useful
      criteria.

PMID- 7524279
TI  - [The concept of biologic progression in metastatic cancer of the prostate
      hormonally treated].
AB  - A total of 110 patients with hormone-treated metastatic prostate cancer were
      monitored quarterly with serial PSA determinations. At the first control, 6
      patients had progressed clinically, 5 of which had decreased PSA ranging between
      9-77%. After a period of response, 69 patients progressed clinically, of which 1
      showed no elevation of PSA levels, 14 showed progression concurrent with PSA
      increase, and 54 showed a period of gradual elevation of PSA over a range of 2-31
      months. The probability of biological progression when the first rise occurred
      ranged between 72-96%, which after a second increase ranged between 92-100%, and
      all patients with three consecutive increases progressed clinically.

PMID- 7524281
TI  - Platelets secrete an eosinophil-chemotactic cytokine which is a member of the C-C
      chemokine family.

PMID- 7524282
TI  - The effects of human recombinant MIP-1 alpha, MIP-1 beta, and RANTES on the
      chemotaxis and adhesion of T cell subsets.

PMID- 7524278
TI  - [Prostate-specific antigen as an evaluation method in the treatment of hormone
      refractory cancer of the prostate].
AB  - Out of 62 patients with hormone-refractory metastatic prostate cancer, 34
      received rescue treatment with estramustine phosphate and 28 received non
      steroidal symptomatic treatment. All patients undergoing symptomatic treatment
      experienced increased PSA levels while in 16 (47%) patients treated with
      estramustine phosphate, PSA decreased between 13-96%. In 11 cases (32.3%) the
      decline in PSA was higher than 50%. In 5 (14.7%) the decline was lower than 50%
      and in 18 cases (53%) PSA levels were increased. SCR rate was 82%, 60% and 6%
      respectively while OCR were 36.4%., 0% and 0% respectively. No clinical response
      was seen in patients undergoing symptomatic treatment. A decline in PSA levels
      higher than 50% 12 weeks after treatment appears to be a "good prognosis" factor
      related to the best clinical response rates and survival.

PMID- 7524283
TI  - Promiscuity of ligand binding in the human chemokine beta receptor family.

PMID- 7524284
TI  - Adhesion molecules in acute and chronic lung inflammation.

PMID- 7524285
TI  - L-arginine/nitric oxide pathway: a possible signal transduction mechanism for the
      regulation of the chemokine IL-8 in human mesangial cells.

PMID- 7524287
TI  - Histamine release induced by glucose (mannose)-specific lectins isolated from
      Brazilian beans. Comparison with concanavalin A.
AB  - The histamine releasing properties of glucose (mannose)-specific lectins isolated
      from Brazilian beans was examined. The Canavalia brasiliensis, Dioclea rostrata,
      and Dioclea virgata lectins induced histamine release in rat peritoneal mast
      cells similar to concanavalin A. Less potency and efficacy was observed for
      Canavalia maritima, Dioclea guianensis, and Dioclea violacea while very low
      activities were seen for the lectins from Dioclea grandiflora, Canavalia
      bonariensis, and Cratylia floribunda. The histamine releasing effect was quenched
      by higher doses of D. virgata lectin similar to what was reported for
      concanavalin A. This effect was abrogated by increasing the concentration of
      calcium in the incubating medium. As these above proteins have sites that bind
      calcium, higher doses of the lectins might withdraw the calcium which is
      essential for the mast cell secretion.

PMID- 7524286
TI  - Basophil activation by members of the chemokine superfamily.

PMID- 7524289
TI  - Pyogenic psoas muscle abscess: report of three cases.
AB  - We report three cases of primary psoas muscle abscess. Two of these cases were
      treated by open drainage through a lumbar incision and the other was by
      ultrasonography (USG)-guided percutaneous aspiration of the abscess. Antibiotic
      therapy was also instituted in all cases. Post-operatively, the patients
      recovered well with no sign of recurrence. USG-guided percutaneous drainage
      combined with appropriate antibiotic therapy appears to be the first choice
      procedure for treatment of the primary psoas abscess if correct diagnosis is
      promptly made and the procedure can be performed.

PMID- 7524290
TI  - [The effect of TZP-4238, an anti-androgen drug, on renal function].
AB  - The effect of TZP-4238, an antiandrogen drug, on renal function was examined.
      Single administration test: Patients with prostatic hypertrophy were divided
      according to creatinine clearance (CCr) into group A (CCr < 50 ml/min) and group
      B (CCr > or = 50 ml/min), and hemodynamics after a single administration of TZP
      4238 were compared between the two groups. Groups A and B showed similar TZP-4238
      hemodynamics, and there was no significant difference in pharmacokinetic
      parameters or the rate of serum protein binding between them. There was no
      difference in the hemodynamics of a major metabolite, 15-OH body, between the two
      groups. Neither was there any significant difference in the urinary excretion
      rate of TZP-4238 or 15-OH body. There were no findings of adverse clinical
      significance, and there were no problems with safety. Consecutive administration
      test: A 16-week consecutive administration study was performed on patients with
      prostatic hypertrophy associated with relative renal hypofunction. The blood
      levels determined in 5 patients were in good accordance with the simulation curve
      drawn from the results of group A. The rates of efficacy, safety and usefulness
      were 71.4%, 90% and 71.4%, respectively. Mild side effects were observed in one
      patient, but the 16-week administration was completed in all patients, and no
      adverse effects on renal function were observed. Favorable blood levels of TZP
      4238 were obtained even in patients with prostatic hypertrophy associated with
      renal hypofunction, and adequate efficacy and safety were achieved even with
      consecutive administration. Furthermore, the drug had no apparent adverse effect
      on renal function.

PMID- 7524288
TI  - Platelet activating factor potentiates rat paw oedema induced by different
      phlogogen agents.
AB  - Carrageenin oedema is enhanced by the simultaneous injection in the rat paw of
      platelet activating factor (PAF). The enhancement of carrageenin oedema is
      observed throughout the time course of the experiments. This enhancement is also
      present when the oedema-producing agent is dextran, cellulose sulphate,
      histamine, 5-hydroxytryptamine, bradykinin or prostaglandin E2. Both verapamil
      and BN 52021 abolished the enhancement induced by PAF without modifying
      significantly carrageenin oedema. In essential fatty acid deficient (EFAD) rats
      depleted of kininogen and amines, carrageenin oedema is not modified by PAF.
      These findings suggest that PAF interacts with other inflammatory mediators
      regulating the formation of oedema induced by irritants injected locally.

PMID- 7524291
TI  - [Study of clinical usefulness of an antiandrogen, TZP-4238, as a drug for
      treatment of benign prostatic hypertrophy--its influence on sexual function].
AB  - Using chlormadinone acetate (CMA) as the control drug, a double-blind study was
      carried out to examine not only the effects of 17 alpha-acetoxy-6-chloro-2-oxa
      4,6-pregnadiene-3,20-dione (TZP-4238;) on subjective urinary symptoms but also,
      especially, that on the sexual function in patients with benign prostatic
      hypertrophy (BPH). The clinical efficacy rate in relation to the subjective
      urinary symptoms was about the same in the two treatment groups; 45.9% in the TZP
      4238 group and 50.0% in the CMA group. However, the incidence of adverse effects
      on the sexual function showed a marked difference between the two groups. The TZP
      4238 group revealed a lower suppressive effect on the function than the CMA group
      (45.1% vs. 71.4%). In relation to their causation of other adverse effects, there
      were no differences between the two drugs. Accordingly, in consideration of the
      facts that TZP-4238 with less influence on the sexual function affords a superior
      quality of life to elderly patients, while achieving effective treatment by means
      of a convenient single daily administration, TZP-4238 was surmised to be a more
      useful drug than CMA as an antiandrogen for the treatment of BPH.

PMID- 7524293
TI  - Assessment of myointimal cellular kinetics in a model of angioplasty by means of
      proliferating cell nuclear antigen expression.
AB  - A detailed temporal assessment of cellular proliferation was carried out by means
      of immunostaining for proliferating cell nuclear antigen in a normolipemic rabbit
      model of balloon angioplasty to the iliac arteries. Assessment was made at 30
      minutes, 2 hours, 1 day, 3 days, 7 days, 14 days, 1 month and 3 months after the
      procedure. Intimal hyperplasia was first noted at day 3; a prominent layer was
      formed by day 14. Cellular proliferation in the vessel media was observed as
      early as day 1 (percentage of positive-staining cells 0.5% +/- 0.2%), reaching a
      maximum by day 7 (16.9% +/- 5.1%) before returning to baseline levels by 1 month
      (0.2% +/- 0.02%); in the intima, cellular proliferation was first noted at day 7
      (0.7% +/- 0.3%) and reached a maximum at day 14 (4.1% +/- 0.4%) before returning
      to baseline levels at 1 month (0.3% +/- 0.1%). Use of proliferating cell nuclear
      antigen expression in this model of angioplasty provided a simple and
      reproducible method of assessing cellular proliferation after vascular injury and
      may prove useful for monitoring the effects, in experimental models, of agents
      for reducing myointimal hyperplasia.

PMID- 7524294
TI  - Improved left ventriculography with the new 5F helical-tip Halo catheter.
AB  - The purpose of this study was to evaluate the incidence of ventricular ectopy and
      catheter movement during left ventriculography with a new 5F halo angiographic
      catheter that has a unique helical-tip design unlike the design of standard 5F
      and 6F pigtail catheters. The pigtail catheter is presently preferred for left
      ventriculography, although its use is associated with a high incidence of
      ventricular ectopy, which often limits precise interpretation of data. In this
      study, 155 patients (in 145 unpaired and 10 paired studies) underwent left
      ventriculography during diagnostic cardiac catheterization. In the unpaired
      group, the 5F Halo catheter was used in 63 studies and standard 5F and 6F pigtail
      catheters in 40 and 42 studies, respectively. An additional 10 patients had two
      consecutive left ventriculograms with 5F Halo and pigtail catheters.
      Ventriculograms were performed with the same technique in the 30-degree right
      anterior oblique projection. The left ventricle was divided into a basal zone,
      midzone, and apical zone. Catheter movement within the ventricle was scored as
      significant if there was at least one zone change. Ventricular ectopy was
      quantified by a simultaneous electrocardiographic recording during contrast
      injection. There were no significant differences in the left ventricular systolic
      or end-diastolic pressures, left ventricular score, or diagnostic quality of the
      ventriculograms between the 5F Halo catheter group and the 5F and 6F pigtail
      catheter groups. Mean ventricular ectopy with the 5F Halo catheter was
      significantly less (0.9 +/- 1.4 ventricular premature beats [VPBs]) than with the
      5F pigtail catheter (2.3 +/- 2.5 VPBs, p < 0.001) or the 6F pigtail catheter (2.9
      +/- 2.9 VPBs, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524292
TI  - [Clinical study of TZP-4238 on patients with benign prostatic hypertrophy--with
      special reference to urodynamics].
AB  - Twenty four cases of benign hypertrophy with bladder outlet obstruction were
      treated with 17 alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione (TZP
      4238), and the effects on urodynamic parameters, clinical efficacy, safety, and
      usefulness were evaluated. Improvement rate of subjective rate of subjective
      symptoms was 52.9%. Obstructive symptoms improved more prominently than
      irritation symptoms. A significant improvement in flow rate of nomograms for
      maximum flow rate (MFR) and average flow rate (AFR) accompanied with the decrease
      in the prostatic weight were observed. However, no changes were observed on the
      urethral sphincter electromyography and the urethral pressure profile. A
      significant decrease of maximum cystometric capacity was observed, although the
      effective cystometric capacity was not changed. The overall improvement rate for
      urodynamic parameters was 43.7%. A significant decrease in weight and diameter of
      the prostate was observed. The prostatic weight decreased in 57.1%, and the
      average reduction rate was 15.4%. The overall improvement rate concerning
      clinical efficacy evaluating both subjective symptoms and objective parameters
      was 58.8%. Adverse reactions were observed in 5 cases. They were judged as not
      clinically problematic. Taking into account clinical safety and clinical
      efficacy, the clinical usefulness was 50.0%. TZP-4238 was considered to be an
      appropriate agent for treating patients with benign prostatic hypertrophy with
      bladder outlet obstruction.

PMID- 7524295
TI  - Malignant arrhythmias and acute myocardial ischemia: interaction between
      flecainide and the autonomic nervous system.
AB  - The antiarrhythmic and proarrhythmic effects of flecainide were assessed in 21
      anesthetized cats. Ventricular arrhythmias can be reproducibly induced in cats by
      the combination of acute myocardial ischemia and sympathetic stimulation.
      Premature ventricular contractions (PVCs), sustained (sVT) and nonsustained
      (nsVT) ventricular tachycardia (VT), or ventricular fibrillation (VF) may be
      induced by a 1-minute left stellate ganglion stimulation during a 3-minute
      coronary artery occlusion. After three trials yielding consistent results,
      flecainide (2 mg/kg intravenous bolus plus 2 mg.kg-1.hr-1 intravenous infusion)
      was injected and two additional trials performed. Eight cats also underwent two
      trials after propranolol (0.2 mg/kg) administered while flecainide infusion was
      maintained. Flecainide decreased heart rate and blood pressure and slightly
      prolonged JTc (9%, p < 0.05). It markedly augmented QRS duration (61%, p <
      0.0001), which was increased by an additional 61% (p < 0.0001) during sympathetic
      stimulation. VF was observed in 8 animals and never after flecainide (p < 0.05).
      However, after drug administration all cats had VT (2 nsVT and 6 sVT), and 5
      required cardiac massage. Flecainide did not prevent the occurrence of nsVT in 6
      cats, and it worsened arrhythmias by inducing VT (4 nsVT and 2 sVT) in 6 cats
      with only PVCs or without arrhythmias in the control trials. Propranolol,
      administered while flecainide infusion was maintained, prevented the increase in
      heart rate and the marked QRS prolongation during sympathetic stimulation (4 +/-
      3 vs 52 +/- 16 msec, p < 0.05) and abolished the proarrhythmic effect of
      flecainide in 4 of 5 animals. Thus flecainide, despite an antifibrillatory
      effect, does not prevent and actually may favor the occurrence of sVT during
      acute myocardial ischemia and enhanced sympathetic activity. Propranolol, by
      countering the increase in heart rate during sympathetic stimulation, prevented
      the rate-dependent conduction delay and abolished the proarrhythmic effect of
      flecainide. The exacerbation, whenever a transient ischemic episode is
      accompanied by elevated sympathetic activity, of the ischemia-induced conduction
      delay caused by flecainide may in part explain the mortality data in the Cardiac
      Arrhythmia Suppression Trial.

PMID- 7524297
TI  - Tubular seminoma. An immunohistochemical and DNA flow-cytometric study of four
      cases.
AB  - The histomorphologic features, immunohistochemical reactivity, and DNA content of
      four cases of a rare tubular variant of seminoma are presented. These neoplasms
      were characterized by a predominantly tubular architectural pattern that
      resembled yolk sac tumor, embryonal carcinoma, and sex cord-stromal tumors. The
      patients' ages were 15, 24, 27, and 44 years. On initial examination, three
      patients had painless testicular enlargement, and one had a large retroperitoneal
      mass and a clinically occult primary testicular tumor. The size of the tumors
      ranged from 1.7 to 6.0 (mean, 4.0) cm. Microscopically, the tumor cells had a
      tubular or tubulopapillary pattern that consisted of a single layer of cells,
      often in a back-to-back arrangement with intervening fibrovascular septa. Areas
      of classic seminoma were present in all cases. Scattered syncytiotrophoblastic
      giant cells were seen in two tumors. The tumor cells of both the classic and the
      tubular components of the seminomas were diffusely positive for placental
      alkaline phosphatase but were negative for cytokeratin and alpha-fetoprotein. DNA
      flow-cytometric analysis demonstrated abnormal stemlines with hypotetraploid DNA
      and a mean DNA index of 1.7 in both the classic and the tubular components. The
      presence of concurrent areas of classic seminoma, similar cytologic features in
      the tubular and classic seminoma areas, and the identical immunohistochemical and
      DNA flow-cytometric findings indicate that tubular seminoma is a histologic
      variant of seminoma. Although the behavior of the tubular variant appeared not to
      differ from that of classic seminoma in our small series, its recognition is
      important in the differential diagnosis and management of testicular masses.

PMID- 7524299
TI  - The spectrum of immunohistochemical staining of small-cell lung carcinoma in
      specimens from transbronchial and open-lung biopsies.
AB  - Immunohistochemistry is increasingly used as an aid in the diagnosis of small
      cell lung carcinoma (SCLC). Previous studies have investigated
      immunohistochemical staining of SCLC with small numbers of antibodies, but few
      have examined large series with a broad panel of antibodies. For this reason, the
      authors examined the distribution and intensity of staining of 20 open-lung
      biopsy (OLB) and 21 transbronchial biopsy (TBB) specimens of SCLC with a panel of
      epithelial, neuroendocrine, and hormonal markers. Small-cell lung carcinoma
      stained most frequently with epithelial markers, followed by neuroendocrine and
      hormonal markers. Similar percentages of OLB and TBB specimens stained for
      keratin (100% each) and epithelial membrane antigen (100% and 95%, respectively).
      Unexpectedly, BER-EP4 stained 100% of OLB specimens. Chromogranin A was the most
      frequent neuroendocrine marker in OLB and TBB specimens (60% and 47%,
      respectively) followed by neuron-specific enolase (60% and 33%), Leu-7 (40% and
      24%), and synaptophysin (5% and 19%). No neuroendocrine immunohistochemical
      reactivity was found in 24% of TBB specimens and 20% of OLB specimens. Bombesin
      was the most sensitive hormonal marker (45% of OLB specimens). These results show
      that keratin, epithelial membrane antigen, and BER-EP4 are reliable epithelial
      markers for SCLC in both TBB and OLB specimens. In addition, negative staining
      for neuroendocrine markers, because it can occur in as many as 25% of cases,
      should not deter the diagnosis of SCLC.

PMID- 7524296
TI  - Exploring the minimal dose of amiodarone with antiarrhythmic and hemodynamic
      activity.
AB  - Amiodarone in doses of 200 to 400 mg/day has shown promise in secondary
      prevention trials for reducing mortality in patients surviving myocardial
      infarction who have complex ventricular ectopy or nonsustained ventricular
      tachycardia, or both. In an attempt to explore the lowest dose of amiodarone with
      antiarrhythmic and hemodynamic activity, we studied 48 patients (mean age 53 +/-
      11 years, ejection fraction 23 +/- 9%, clinical heart failure in 85%) with
      nonsustained ventricular tachycardia. This was a 3-month, randomized, parallel,
      double-blind pilot study comparing placebo (n = 16) with amiodarone 50 mg/day (n
      = 15) and 100 mg/day (n = 17). Patients randomized to amiodarone received a mean
      loading dose of 422 mg/day for the first study week. At the end of the 12 weeks,
      amiodarone (100 mg) significantly reduced ventricular premature complexes (177 +/
      64 to 98 +/- 38/hour), couplets (8 +/- 3 to 4 +/- 2/hour), and runs of
      nonsustained ventricular tachycardia (13 +/- 7 to 3 +/- 2/day), all p < 0.01
      versus baseline. In addition, 10 of 14 patients taking 100 mg/day had total
      suppression of nonsustained ventricular tachycardia compared with 4 of 15 taking
      placebo, p = 0.021. Left ventricular ejection fraction improved by > or = 7%
      (absolute) in 11 of 29 patients taking amiodarone as compared with only 1 of 15
      placebo patients (p = 0.02). In these 11 patients with the greatest measurable
      hemodynamic improvement, amiodarone significantly increased ejection fraction (21
      +/- 7% to 33 +/- 11%, p < 0.01), stroke volume index (28 +/- 9 to 40 +/- 7 ml/m2,
      p < 0.01) and decreased end-systolic volume index (116 +/- 48 to 92 +/- 44 ml/m2,
      p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524300
TI  - Fine-needle aspiration cytologic diagnosis of Kikuchi's lymphadenitis. A report
      of 27 cases.
AB  - Kikuchi's lymphadenitis is a self-limiting condition typically affecting young
      patients. Surgical biopsy is unnecessary if a firm diagnosis can be rendered by
      fine-needle aspiration cytology (FNAC). The authors report the FNAC findings for
      27 cases, including 24 female and 3 male patients aged 12 to 43 years. Histologic
      sections of FNAC cell blocks and excisional biopsy specimens were available in 26
      and 9 cases, respectively, for confirmation of the diagnosis. In the smears,
      karyorrhectic and granular debris were mixed with two distinctive cell types: (1)
      phagocytic histiocytes with peripherally placed "crescentic" (sometimes elongated
      or twisted) nuclei and abundant cytoplasm containing phagocytosed karyorrhectic
      or eosinophilic granular debris, easily distinguishable from tangible-body
      macrophages, which possessed central round nuclei, and (2) medium-sized cells
      possessing eccentrically placed round nuclei, fairly condensed chromatin, and a
      moderate amount of amphophilic cytoplasm, consistent with plasmacytoid monocytes.
      Also present were nonphagocytic histiocytes with twisted nuclei and delicate
      chromatin and immunoblasts that sometimes showed atypical features such as
      irregular foldings of the nuclei. Neutrophils were sparse or absent. Review of
      the FNAC findings of 50 lymph nodes involved by various reactive processes,
      tuberculosis, and lymphoma for comparison showed that although tangible-body
      macrophages and debris were not uncommon, very few phagocytic histiocytes with
      crescentic nuclei were observed, in only 2 cases; plasmacytoid monocytes were
      observed in 4 cases. The constellation of features described above permits
      diagnosis of Kikuchi's lymphadenitis by FNAC. Because of morphologic similarities
      between lupus lymphadenitis and Kikuchi's lymphadenitis, however, serologic
      studies are warranted to exclude systemic lupus erythematosus.

PMID- 7524298
TI  - Diffuse embryoma of the testis. An immunohistochemical study of two cases.
AB  - The authors report the histologic and immunohistochemical findings of two cases
      of diffuse embryoma of the testis, a distinct form of mixed-germ-cell tumor
      characterized by diffuse, orderly arrangement of embryonal carcinoma (EC) and
      yolk sac tumor (YST) with scattered trophoblastic components. The patients were
      37 and 38 years old when they presented with a right testicular tumor, which was
      confined to the testis (stage I) in both cases. Histologically, the tumor was
      composed predominantly of intimately intermingled EC and YST components in almost
      equal proportion. The tumor cells were arranged in necklacelike fashion; the EC
      cells formed glandular structures rimmed by a single cell layer of YST cells. The
      YST component was highlighted by positive staining for alpha-fetoprotein and
      strong staining for cytokeratin, whereas the EC component was positive for Ki-1
      (BerH2, CD30) antigen, was negative for alpha-fetoprotein, and stained more
      weakly for cytokeratin. The randomly distributed few trophoblastic elements
      stained for human chorionic gonadotropin. The patients are alive with no evidence
      of disease, 11 years and 9 months after surgery, respectively. This newly
      described but distinct variant of mixed-germ-cell tumor should be differentiated
      from polyembryoma, which is composed of multiple discrete embryoid bodies.

PMID- 7524302
TI  - CD20+ T-cell lymphoma. Neoplastic transformation of a normal T-cell subset.
AB  - CD20 is a 35-kDa protein that is expressed early in B-cell ontogeny and is lost
      during terminal B-cell differentiation into plasma cells. It is thought to be B
      cell-specific. However, the CD20 antigen, detected by the monoclonal antibody
      L26, has been reported in some cases of T-cell lymphoma. This report describes a
      case of a malignant lymphoma coexpressing T-cell-lineage antigens and CD20 and
      characterization of a CD20+ T-cell population in the peripheral blood of healthy
      donors. The tumor cells were pleomorphic medium-sized cells that expressed a
      range of T-cell-specific antigens, including CD2, CD3, CD4, CD5, CD6, CD7, and
      beta F1. In addition, the tumor cells expressed CD20 on frozen (B1) and paraffin
      sections (L-26). Stains for other pan-B cell antigens, including CD19 and CD22,
      and immunoglobulin light and heavy chains were negative. To determine whether
      this unusual coexpression of T-cell-lineage antigens and CD20 represented
      aberrant antigen expression or neoplastic transformation of an unusual normal T
      cell subset, the authors examined specimens of peripheral blood lymphocytes from
      healthy donors for evidence of a CD20+ T-cell population by using three-color
      immunofluorescence analysis by flow cytometry. Two distinct populations of CD20+
      cells were observed in peripheral blood. One expressed bright CD20 (6.6% to
      23.7%, mean 14.47% of peripheral blood lymphocytes) and other B-cell associated
      antigens, whereas the other expressed dim CD20 (.94% to 11.90%, mean 3.50% of
      peripheral blood lymphocytes) and coexpressed CD3. Approximately two thirds
      (52.8% to 82.3%, mean 64.1%) of the dim CD20 cells were CD8+ and one third (19.2%
      to 74.1%, mean 37.5) CD4+. These cells also expressed CD5 and the alpha-beta
      chain of the T-cell receptor and lacked CD19 and CD22. These results indicate
      that CD20 is expressed on some normal peripheral blood T cells. CD20 expression
      by T-cell lymphomas may represent neoplastic transformation of a normal subset of
      CD20+ T cells rather than aberrant antigen expression by neoplastic cells. The
      nature of the CD20 antigen on T cells and the function of the normal population
      remain to be determined.

PMID- 7524303
TI  - Detection of human cytomegalovirus, Epstein-Barr virus, and herpes simplex virus
      in diffuse interstitial pneumonia by polymerase chain reaction and
      immunohistochemistry.
AB  - Using formalin-fixed and paraffin-embedded tissues from autopsy, the authors
      examined infection by human cytomegalovirus, Epstein-Barr virus, and herpes
      simplex virus in 54 patients with primary or secondary diffuse interstitial
      pneumonia (DIP) by polymerase chain reaction and immunohistochemistry and
      compared it with that in 32 persons without lung complications. Polymerase chain
      reaction and immunohistochemistry demonstrated that approximately 40% and 30% of
      DIP were positive for human cytomegalovirus and Epstein-Barr virus, respectively,
      but none of 32 controls had evidence of infection by human cytomegalovirus and
      Epstein-Barr virus. The polymerase chain reaction was more sensitive than the
      immunohistochemical technique for detection of herpes simplex virus. The former
      technique revealed herpes simplex virus infection in approximately 90% of DIP and
      controls and the latter in approximately 50% of each group. However,
      immunohistochemistry had the advantage of demonstrating the morphologic location
      of infected cells and of allowing their semiquantitative evaluation. Herpes
      simplex virus was more extensively distributed in the lungs of several DIP cases
      than in those of controls, suggesting the reactivation of herpes simplex virus.
      Only DIP patients (31 cases [57.4%]) were infected by two or three kinds of
      herpesviruses. The combination of polymerase chain reaction and
      immunohistochemistry revealed that these herpesviruses proliferated in many cases
      of DIP.

PMID- 7524301
TI  - Bcl-2 oncogene protein is preferentially expressed in Reed-Sternberg cells in
      Hodgkin's disease of the nodular sclerosis subtype.
AB  - One hundred three cases of nodular sclerosis (NS) and mixed-cellularity Hodgkin's
      disease were evaluated for expression of bcl-2 oncogene protein, because previous
      studies have revealed expression of bcl-2 in these subtypes but only rarely in
      the nodular lymphocyte-predominance subtype. Reed-Sternberg (RS) cells and
      lacunar variants were positive for bcl-2 in 51 of 86 NS cases and 4 of 17 mixed
      cellularity cases. In individual cases of NS, the percentage of RS cells and
      lacunar variants positive for bcl-2 ranged from minimal (in 5 cases) to 100%
      positive (mean, 34%). By univariate analysis, expression of the bcl-2 gene
      product in RS cells was observed in a significantly greater proportion of NS
      Hodgkin's disease cases than MC cases (P < .009), a finding that may have
      implications on the pathogenesis of this disorder.

PMID- 7524304
TI  - Coccoid forms of Helicobacter pylori in the human stomach.
AB  - Helicobacter pylori (HP) may transform from helical bacillary forms to coccoid
      forms after several days' in vitro incubation. The authors examined 111
      consecutive gastrectomy specimens for the presence of coccoid forms of H pylori.
      Tissues from 64 stomachs (57.7%) showed colonization by H pylori, including 49
      cases (76.6%) of adenocarcinoma, 14 cases (21.9%) of benign peptic ulcer, and 1
      case (1.6%) of malignant lymphoma. Of these, coccoid forms of H pylori were
      identified in 53 cases (82.8%). In hematoxylin-and-eosin-stained sections coccoid
      forms of H pylori appeared as solid, round, basophilic dotlike structures. Under
      an electron microscope, coccoid forms of H pylori appeared as U-shaped bacilli,
      with the ends of the two arms joined by a membranous structure. Ultrastructural
      findings were identical to those from cultures of H pylori. With anti
      Helicobacter antibody, coccoid forms of H pylori were positively stained by
      immunoperoxidase. Helical bacillary forms of H pylori invariably coexisted with
      the coccoid forms. By semiquantitative analysis, the number of coccoid forms in
      adenocarcinoma was significantly (P > .01) greater than that in benign peptic
      ulcers. This study confirms that H pylori can exist in coccoid forms in the human
      stomach. Coccoid forms should be distinguished from the pathogenic or
      nonpathogenic bacterial cocci, fungal spores, and cryptosporidia that may
      colonize the human stomach.

PMID- 7524305
TI  - Prostate-specific antigen. Current role in diagnostic pathology of prostate
      cancer.
AB  - Prostate-specific antigen is the most important, accurate, and clinically useful
      biochemical marker in the prostate. It is manufactured by the secretory
      epithelial cells and drains into the ductal system, where it catalyzes the
      liquefaction of the seminal coagulum after ejaculation. Serum levels are normally
      less than 4 ng/mL (monoclonal) but vary according to patient age and race; any
      process that disrupts the normal architecture of the prostate allows diffusion of
      prostate-specific antigen into the stroma and microvasculature. Elevated serum
      prostate-specific antigen levels are seen with prostatitis, infarcts,
      hyperplasia, and transiently after biopsy, but the most clinically important
      increases are seen with prostatic adenocarcinoma. Cancer produces less prostate
      specific antigen per cell than benign epithelium, but the greater number of
      malignant cells and the stromal disruption associated with cancer account for the
      increased serum prostate-specific antigen level. Serum prostate-specific antigen
      level correlates positively with clinical stage, tumor volume, histologic grade,
      and the presence of capsular perforation and seminal vesicle invasion; despite
      these strong correlations, its value is limited in predicting stage for
      individual patients. It may also predict the presence of lymph node metastases,
      bone metastases, and survival after androgen-deprivation therapy. The use of
      prostate-specific antigen has resulted in an increase in the early detection rate
      of cancer, and it is now advocated for annual routine use in men older than 40
      years who are at increased risk and in all men older than 50 years. It is a test
      with high sensitivity and specificity that is rapid, inexpensive, minimally
      invasive, and acceptable to patients. In addition to serum prostate-specific
      antigen level, five derivatives of serum prostate-specific antigen were recently
      described that may increase the predictive value by accounting for confounding
      variables such as patient age, prostate volume, and cancer volume: age-specific
      reference ranges, prostate-specific antigen density, prostate-specific antigen
      velocity, prostate-specific antigen cancer density, and prostate-specific antigen
      doubling times. Serum prostate-specific antigen detects a heterogeneous group of
      cancers (clinical stage T1c) that are clinically important and potentially
      curable. Immunohistochemical expression of prostate-specific antigen in tissue
      sections allows determination of the prostatic origin of some metastatic
      adenocarcinomas, although extraprostatic expression of prostate-specific antigen
      has been reported in several tissues and tumors, including periurethral gland
      adenocarcinoma in women, rectal carcinoid, and extramammary Paget
      disease.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7524306
TI  - Grading prostate cancer.
AB  - Histologic tumor grade is a strong predictor of outcome for men with prostate
      cancer. All existing grading systems successfully identify well-differentiated
      cancer, which progresses slowly, and poorly differentiated cancer, which
      progresses rapidly, but they are less successful in subdividing most moderately
      differentiated cancers, which have an intermediate malignant potential. The
      Gleason system, the de facto standard for grading, identifies histologic patterns
      by the degree of glandular differentiation without relying on morphogenetic or
      histogenetic models; it reflects tumor heterogeneity by combining primary and
      secondary patterns into a cancer score. Modifications that have been proposed for
      Gleason grading include morphometric nuclear grading, grouping of grades,
      estimating the amount of high-grade cancer (Gleason patterns 4 and 5), and
      including the cribriform pattern as Gleason pattern 4 rather than 3. Most
      variants of prostate cancer are high grade (Gleason patterns 4 and 5), including
      small cell undifferentiated carcinoma, signet ring cell carcinoma, sarcomatoid
      carcinoma, and carcinosarcoma. The Gleason system can be reproduced by most
      investigators, although there is a small but significant level of interobserver
      and intraobserver variability that is unavoidable. When compared with matched
      prostatectomy specimens, contemporary 18-gauge needle core biopsy underestimates
      tumor grade in 33% to 45% of cases and overestimates grade in 4% to 32% of cases,
      similar to results with traditional 14-gauge biopsies. Grading errors are common
      in biopsy specimens with small amounts of tumor and low-grade tumor, and are
      probably due to tissue sampling error and tumor heterogeneity. Upgrading of
      prostate cancer may occur after radiation therapy but is common after androgen
      deprivation therapy. Univariate and multivariate analyses of prognosis in
      prostate cancer almost always identify cancer grade as one of the most
      significant predictors of patient outcome. The combination of cancer grade with
      other prognostic variables to create a multiple prognostic index should allow
      greater precision in predicting outcome for individual patients.

PMID- 7524307
TI  - Terminal deoxynucleotidyl transferase staining in acute leukemia and normal bone
      marrow in routinely processed paraffin sections.
AB  - Terminal deoxynucleotidyl transferase (TdT) is a nuclear protein widely used as a
      marker for the diagnosis and classification of acute leukemia. The usual methods
      for detecting TdT require smears, imprints, or cryostat sections of unfixed
      tissue. A polyclonal rabbit anti-TdT serum was used to immunostain 54 routinely
      processed bone marrow sections from patients with acute leukemic disorders, using
      a recently described antigen-unmasking technique based on microwave oven heating.
      The specificity of this method of TdT analysis was confirmed by comparing the
      results obtained with conventional TdT analysis by indirect immunofluorescence.
      Terminal deoxynucleotidyl transferase reactivity was also evaluated in 44
      nonmalignant and normal bone marrow specimens. All cases that were TdT-positive
      by immunofluorescence (41 of 42 "pre-B" and T-cell acute lymphoblastic leukemia,
      2 of 5 acute myeloid leukemia, and 1 of 5 chronic myeloid leukemia in blast
      crisis) were also positive in paraffin sections. The percentage fluorescence
      positivity correlated with the percentage of immunoperoxidase stained cells in 44
      of 45 cases. The remaining nonneoplastic and normal bone marrow biopsy specimens
      were TdT-negative. These results show that TdT immunoperoxidase staining of
      conventionally processed bone marrow specimens can be readily achieved by the use
      of a simple antigen-unmasking technique and may provide useful diagnostic
      information particularly in cases in which fresh tissue samples are unavailable.

PMID- 7524309
TI  - Palliation for extrahepatic biliary obstruction by metastatic colorectal
      carcinoma.
AB  - OBJECTIVES: Extrahepatic biliary obstruction due to metastatic colorectal
      carcinoma, though rare, can account for the occurrence of obstructive jaundice
      even in the presence of hepatic metastases. The present report aims at reviewing
      our experience with the palliative treatment of these patients. METHODS: During a
      5-yr period, 11 patients with obstructive jaundice had documented extrahepatic
      biliary obstruction secondary to metastatic colorectal carcinoma. Their clinical
      records were retrospectively analyzed. RESULTS: Nonoperative drainage was
      performed in eight patients by either the endoscopic (n = 5) or percutaneous (n =
      3) route. Palliation was achieved in six patients with a mean hospital stay of
      24.5 days (14% of survival). Three patients died of hepatorenal failure before a
      drainage procedure could be performed. Blocked stent and cholangitis were noted
      in two patients. The mean survival was 5 months in the drainage group.
      CONCLUSIONS: The occurrence of obstructive jaundice in patients with metastatic
      colorectal carcinoma deserves routine investigation to exclude extrahepatic
      biliary obstruction. Endoprosthesis insertion by nonoperative means should be
      considered for palliation.

PMID- 7524308
TI  - MIC2 analysis of small cell carcinoma.
AB  - Small cell carcinomas (SCCs) and peripheral neuroectodermal tumors (PNETs) are
      two distinct neoplasms that show considerable histologic, immunohistochemical,
      and clinical overlap, but differ in their therapies and prognoses. In an attempt
      to further diagnostically distinguish the two, 33 SSCs were analyzed from both
      pulmonary and extrapulmonary sites for the MIC2 gene product, a cell surface
      antigen strongly and reliably expressed in PNETs and Ewing's sarcoma (ES). Two of
      the 33 SCCs stained positively, but the staining was less intense than that seen
      with PNET and ES. The remaining 31 tumors did not stain. These data indicate
      that, in combination with a panel of immunohistochemical stains, analysis of
      neuroendocrine tumors for MIC2 expression may be useful in distinguishing between
      small cell carcinomas of both pulmonary and extrapulmonary origins and soft
      tissue PNETs.

PMID- 7524312
TI  - The use of oral fluid for hepatitis C antibody screening.
AB  - OBJECTIVES: To assess the efficacy of oral fluid antibody testing for the
      detection of hepatitis C. METHODS: Paired serum and oral fluid collections were
      obtained from 216 subjects. A modification of the serum HCV ELISA assay was
      developed to improve test accuracy for an oral fluid substrate. Sensitivity was
      determined in 109 HCV serum ELISA-positive patients and specificity in 107 HCV
      serum ELISA-negative patients. RESULTS: Overall sensitivity of oral fluid
      collection and testing was 98.2%; specificity was 99.1%. These parameters did not
      seem to be altered by presence of concurrent hepatitis B infection, inflammatory
      state of the liver, or other factors. CONCLUSIONS: Oral fluid collection and HCV
      antibody testing by the modified ELISA method seems to be an effective and
      efficient alternatives to venipuncture and serum HCV antibody testing. Their use
      may facilitate epidemiological surveys and evaluation of individual patients when
      blood collection is not feasible.

PMID- 7524311
TI  - Hypocomplementemia associated with hepatitis C viremia in sera from voluntary
      blood donors.
AB  - OBJECTIVES: Hepatitis C virus (HCV) infection induces extra-hepatic
      manifestations, most of which are considered to be mediated by circulating immune
      complexes. For evaluating this association in a wider perspective, complement
      activity was determined in sera from apparently healthy individuals, and
      hypocomplementemia was tested for correlation with HCV viremia. METHODS: Sera
      from 10,532 voluntary blood donors were stored at 4 degrees C overnight, serially
      diluted 2-fold, and tested for hemolytic activity by a microtitration method and
      antibody to HCV (anti-HCV) by passive hemagglutination with recombinant HCV
      antigens of the second generation. HCV RNA was determined in sera with anti-HCV
      or hypocomplementemia, or both, by polymerase chain reaction with nested primers
      deduced from the 5'-noncoding region of the HCV genome. RESULTS:
      Hypocomplementemia was detected in 53 (0.5%) of 10,532 donations and anti-HCV in
      94 (0.9%). Anti-HCV was detected in 48 (91%) of the 53 sera with
      hypocomplementemia, more frequently than in 46 (0.44%) of 10,479 sera without (p
      < 0.001). Among 94 sera positive for anti-HCV, HCV RNA was detected in 45 (94%)
      of 48 sera with hypocomplementemia, more often than in 10 (22%) of 46 sera
      without (p < 0.001). CONCLUSIONS: A close association of hypocomplementemia with
      HCV viremia among apparently healthy blood donors would reflect circulating
      immune complexes which may cause extrahepatic diseases, such as cryoglobulinemia
      and membranoproliferative glomerulonephritis, in some HCV carriers. The storage
      of sera from HCV carriers at 4 degrees C before the test would have contributed
      to a decreased hemolytic activity due to the cold activation of complement by
      cryoglobulins involving HCV.

PMID- 7524310
TI  - Innervation of an esophageal ectatic submucosal blood vessel in achalasia and a
      comparison with normals.
AB  - Achalasia is a disease of the esophagus characterized by incomplete relaxation of
      the lower esophageal sphincter, resulting in obstruction. Aperistalsis and
      dilation of the esophageal body occurs later, contributing to the esophageal
      dysfunction. Gastrointestinal bleeding in achalasia is an infrequent complication
      usually caused by stasis ulcer, esophageal varices, carcinoma, or pneumatic
      dilation of the sphincter. We describe here a patient with longstanding achalasia
      who bled vigorously from a proximal esophageal site that can be identified as
      arterial bleeding by endoscopy. Subsequent esophageal resection allowed detailed
      histological and immunohistochemical examination, which revealed a vascular
      ectasia. This lesion was associated with an unusually rich network of nerve
      fibers containing calcitonin gene-related peptide. Neuropeptide Y- and substance
      P-containing fibers were found to be decreased in this lesion as compared with
      controls. On the other hand vasoactive intestinal peptide- and nitric oxide
      synthase-containing fibers appeared quantitatively similar to those of controls.
      Calcitonin gene-related peptide is known to be involved in angiogenesis and may
      have played a causative role in the development of this lesion. Vascular ectasia
      may represent a hitherto unreported complication of achalasia.

PMID- 7524313
TI  - Fresh frozen plasma has no beneficial effect on the hemostatic system in children
      receiving L-asparaginase.
AB  - L-Asparaginase (ASP), a chemotherapeutic agent used in the treatment of children
      with acute lymphoblastic leukaemia (ALL), is linked to thromboembolic
      complications secondary to an acquired deficiency of antithrombin III (ATIII).
      Fresh frozen plasma (FFP) is used to prevent and/or treat thrombotic
      complications in these children. However, the effect of FFP on plasma
      concentrations of ATIII and biochemical markers of activation of coagulation has
      never been tested. In this study, FFP (20 ml/kg) was administered to eight
      children with ALL receiving ASP in the consolidation phase of their treatment.
      Plasma samples were drawn pre-infusion, and following infusion at 1, 24, and 48
      hr. Prior to the FFP infusions, plasma concentrations of prothrombin, fibrinogen,
      alpha 2-macroglobulin, heparin cofactor II, protein C, and protein S were similar
      to levels in healthy children. Only plasma concentrations of ATIII were
      significantly decreased (0.55 U/ml). Following FFP infusions, there was no
      statistical or clinically important increase in plasma concentrations of any
      coagulation protein at any time point. Pre-infusion plasma concentrations of
      markers of endogenous thrombin generation (thrombin-antithrombin III complexes
      (TAT)) and activation of the fibrinolytic system in response to activation of the
      coagulation system (D-dimer levels) were significantly increased. However, FFP
      had no statistical or clinically important effect on concentrations of these
      markers. We conclude that FFP administration for the prevention and treatment of
      acquired ATIII deficiency secondary to ASP has no demonstrable benefit on plasma
      levels of coagulation proteins and is unlikely to be of clinical benefit.

PMID- 7524314
TI  - Effect of desferrioxamine and hydroxypyridones on hemopoietic progenitors and
      neuroectodermal tumor cells.
AB  - The iron chelator desferrioxamine (DFO) has been shown to inhibit the
      proliferation of hemopoietic progenitors and several tumor cell lines. We have
      compared the in viro hemopoietic inhibitory effect of desferrioxamine (DFO) and
      hydroxypyridones (HPOs) on hemopoietic progenitors and two human neuroectodermal
      (NE) tumor cell lines, NB 100 and SKNMC. Both DFO and HPOs showed a direct dose
      related inhibitory effect on BFU-E and CFU-GM obtained from purified human non-T
      MNAC (T-lymphocyte-depleted nonadherent mononuclear cells) and CD34+ cells. DFO
      and HPOs displayed both an inhibitory and a cytotoxic effect on NE cell lines. We
      calculated the ratio between NE cell and hemopoietic cell growth inhibition for a
      range of concentrations of chelators. DFO showed the most satisfactory ratio.
      This suggests that DFO is still the most preferable chelating agent for the
      treatment of neuroblastoma, since it combines the highest antineuroblastoma
      effect with the lowest hematopoietic toxicity.

PMID- 7524316
TI  - Miles introduces agent for reducing blood-transfusion requirements.

PMID- 7524317
TI  - Tacrolimus introduced for use in liver transplantation.

PMID- 7524318
TI  - Blood tacrolimus concentration unchanged by plasmapheresis.

PMID- 7524315
TI  - Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations
      in the aquaporin 2 water-channel gene.
AB  - Mutations in the X-chromosomal V2 receptor gene are known to cause nephrogenic
      diabetes insipidus (NDI). Besides the X-linked form, an autosomal mode of
      inheritance has been described. Recently, mutations in the autosomal gene coding
      for water-channel aquaporin 2 (AQP2) of the renal collecting duct were reported
      in an NDI patient. In the present study, missense mutations and a single
      nucleotide deletion in the aquaporin 2 gene of three NDI patients from
      consanguineous matings are described. Expression studies in Xenopus oocytes
      showed that the missense AQP2 proteins are nonfunctional. These results prove
      that mutations in the AQP2 gene cause autosomal recessive NDI.

PMID- 7524319
TI  - Compatibility of filgrastim with selected drugs during simulated Y-site
      administration.
AB  - The compatibility of filgrastim with selected drugs during simulated Y-site
      injection was studied. Five-milliliter samples of filgrastim 30 micrograms/mL in
      5% dextrose injection were combined with 5-mL samples of solutions of each of 97
      other drugs in 5% dextrose injection at clinically used concentrations at 22
      degrees C. Immediately after and one and four hours after the samples were
      combined, visual examinations were performed in fluorescent light with the
      unaided eye and with a high-intensity monodirectional light (Tyndall beam) to
      enhance the visualization of small particles and low-level turbidity. The
      turbidity of each drug combination was measured as well. Combinations yielding
      inconclusive results were subjected to particle sizing and counting. Most of the
      drugs tested were compatible with filgrastim 30 micrograms/mL during the
      observation period. However, 22 drugs showed various incompatibilities with
      filgrastim, including filament formation, particulate formation and
      precipitation, and color change. Filgrastim 30 micrograms/mL in 5% dextrose
      injection was compatible with 75 drugs for up to four hours at 22 degrees C; 22
      drugs were not compatible with filgrastim.

PMID- 7524320
TI  - Towards identification of X-linked mental retardation genes: a proposal.
AB  - Identification of X linked mental retardation (XLMR) genes that can only be
      broadly localised by linkage analysis will ultimately depend on systematic
      screening of many probands for mutations in many candidate genes. This would be
      more efficiently performed by analysis of mRNA (or illegitimate transcripts) by
      reverse transcriptase-polymerase chain reaction (RT-PCR). A scheme is proposed
      that associates standardized reporting of XLMR families, including small families
      that would not by themselves yield statistically significant linkage information,
      and deposit of a lymphoblastoid cell line for one proband of each family to an
      accessible repository.

PMID- 7524321
TI  - Unexplained elevated maternal serum alpha-fetoprotein levels and perinatal
      outcome in an urban clinic population.
AB  - OBJECTIVE: Our purpose was to determine whether obstetric patients with
      unexplained elevated maternal serum alpha-fetoprotein levels from an indigent
      clinic population are at increased risk for adverse perinatal outcome compared
      with similar patients with normal values. STUDY DESIGN: Perinatal outcomes from
      inner-city obstetric patients with unexplained elevated maternal serum alpha
      fetoprotein levels (> 2.0 multiples of the median) were compared with patients
      from the same clinic with normal values. The frequency of adverse outcomes in the
      two groups was subjected to chi 2 analysis. RESULTS: Adverse perinatal outcomes
      occurred in 33 of 57 (58%) of the subjects with unexplained elevated maternal
      serum alpha-fetoprotein levels compared with 163 of 719 (23%) patients with
      normal values (p < 0.001). Statistically significant differences were observed
      for abruptio placentae (p < 0.025), intrauterine growth retardation (p < 0.025),
      stillbirth at > 20 weeks (p < 0.001), and pregnancy-induced hypertension (p <
      0.01). Differences in the frequencies of preterm premature rupture of membranes,
      preterm delivery, pregnancy loss < 20 weeks, and congenital malformations were
      not statistically significant. CONCLUSION: In contrast to a previous report, we
      found that unexplained elevated maternal serum alpha-fetoprotein levels confer an
      increased risk of adverse perinatal outcome in an urban clinic population over
      and above the already increased risk related to socioeconomic status.

PMID- 7524322
TI  - Elevated second-trimester human chorionic gonadotropin levels in association with
      poor pregnancy outcome.
AB  - OBJECTIVE: Our purpose was to determine whether abnormal pregnancy outcome is
      associated with elevated maternal serum human chorionic gonadotropin levels.
      STUDY DESIGN: Maternal serum alpha-fetoprotein and human chorionic gonadotropin
      levels were measured in stored second-trimester serum obtained before scheduled
      genetic amniocentesis from 126 women with poor pregnancy outcomes, excluding
      aneuploidy and structural abnormalities (complications group), and 126 matched
      women with normal outcomes (control group). RESULTS: More women with
      complications had elevated human chorionic gonadotropin levels (> or = 2.0
      multiples of the median) (14%) than did control women (3%) (p = 0.01). Both
      elevated human chorionic gonadotropin and maternal serum alpha-fetoprotein levels
      were significantly associated with preterm delivery and fetal death. Elevated
      maternal serum alpha-fetoprotein was significantly associated with early
      postamniocentesis complications and fetal growth restriction, whereas elevated
      human chorionic gonadotropin was associated with preeclampsia. CONCLUSION:
      Elevated human chorionic gonadotropin, similar to unexplained elevated maternal
      serum alpha-fetoprotein, is significantly associated with abnormal pregnancy
      outcomes.

PMID- 7524323
TI  - The utility of fetal biometry as an adjunct to the multiple-marker screening test
      for Down syndrome.
AB  - OBJECTIVE: Our purpose was to investigate fetal biometry as an adjunct to the
      multiple-marker screen (maternal age, serum alpha-fetoprotein, estriol, and human
      chorionic gonadotropin) for Down syndrome. STUDY DESIGN: Fifty-two cases of Down
      syndrome were compared with 7514 normal fetuses. The measured/predicted femur
      length ratio had the best discriminant value (1.0 +/- 0.11 vs 0.93 +/- 0.13, p <
      0.0001). Multivariate gaussian algorithms were developed and each computed a
      likelihood ratio for Down syndrome. The trivariate algorithm incorporated the
      three maternal analytes, whereas the quadrivariate version also included the
      femur length ratio. The study population included 38 cases of Down syndrome and
      1098 euploid controls. The midtrimester risk was the product of the age-related
      risk and the likelihood ratio. RESULTS: The relative difference in the femur
      length ratio between normal and affected fetuses was small in comparison to that
      of the maternal serum analytes. At a risk cutoff of > or = 1:190 the detection
      rates were similar and actually favored the trivariate algorithm but differed
      only by one case of Down syndrome. CONCLUSION: The addition of the
      measured/predicted femur length ratio had a negligible effect on the performance
      of the multiple-marker screening test.

PMID- 7524324
TI  - Risk of anomalies as a function of level of elevated maternal serum alpha
      fetoprotein.
AB  - OBJECTIVE: Most neural tube defects risks are not actual but mathematical
      extrapolations. We sought to evaluate this risk and to compare actual
      performance. STUDY DESIGN: This was a retrospective study of a referral
      population with elevated maternal serum alpha-fetoprotein results between 1987
      and 1992. Ultrasonography results, delivery records, and autopsy results were
      compared with entry levels of maternal serum alpha-fetoprotein, and the
      percentage of fetal anomalies detected in this study was evaluated. RESULTS: A
      total of 773 patients with elevated maternal serum alpha-fetoprotein levels were
      evaluated. There was a progressive increase in the incidence of anomalies as a
      direct function of the level of the maternal serum AFP, varying from 3.4% at a
      level of 2.5 to 40.3% at a level > 7.0. CONCLUSION: Data from this study support
      the correlation of maternal serum AFP levels with the risk of neural tube defect
      and ventral wall defects.

PMID- 7524326
TI  - Fetal cells in maternal blood: determination of purity and yield by quantitative
      polymerase chain reaction.
AB  - OBJECTIVE: The detection of fetal aneuploidy and gene mutations by analysis of
      fetal cells in maternal blood has demonstrated the feasibility of noninvasive
      prenatal diagnosis. Fetal cells are rare in the maternal circulation; all current
      methods used for their isolation also yield maternal cells. We developed a method
      that permits a quantitative assessment of the relative numbers of fetal and
      maternal cells. STUDY DESIGN: Samples from 40 pregnant women were flow sorted
      with different monoclonal antibodies. Deoxyribonucleic acid was subsequently
      purified from candidate fetal cells; polymerase chain reaction was performed with
      synthetic primers specific for sequences on chromosomes Y and 7. RESULTS: The
      maximum number of fetal cells detected was 52 in 1080 maternal cells. Fetal cell
      purity ranged from 0.001% to 4.8%. Fetal cells were detected with antibodies to
      CD71, CD36, and glycophorin A. CONCLUSION: Quantitative polymerase chain reaction
      enables the determination of the purity and yield of fetal cells remaining after
      isolation from maternal blood, facilitating rapid comparisons between different
      cell separation techniques.

PMID- 7524327
TI  - Somatosensory processing abilities of very low-birth weight infants at school
      age.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      somatosensory processing abilities of children at school age and their earlier
      experiences in the intensive care nursery as very low-birth weight (VLBW)
      infants. METHOD: The subjects were 35 VLBW children at school age (20 girls, 15
      boys) who were free of congenital deformity and developmentally appropriate for
      gestational age. The subjects were part of an ongoing longitudinal study. Birth
      weight, number of days supported by mechanical ventilation, and number of days in
      the neonatal intensive care unit were examined in relation to somatosensory
      functions. Somatosensory functions measured were manual form perception,
      kinesthesia, finger identification, graphesthesia, and localization of tactile
      stimuli. RESULTS: VLBW children were significantly different on all measures of
      somatosensory processing when compared with the standardization group.
      CONCLUSION: Further research on the VLBW infant's somatosensory functioning will
      add to the existing body of knowledge concerning development and guide practice.
      The finding that the infants in this study, who did not have therapy
      intervention, later presented diminished somatosensory functioning supports the
      need to develop measures of somatosensory development for use in assessments and
      treatment during all developmental phases.

PMID- 7524328
TI  - Predicting outcome in high-risk newborns with a neonatal neurobehavioral
      assessment.
AB  - OBJECTIVES: Effective medical management and rehabilitation efforts in neonates
      at risk depend on early identification of underlying brain injury. The aim of
      this study was to determine the prognostic value of the Einstein Neonatal
      Neurobehavioral Assessment Scale (ENNAS) in high-risk neonates, and to compare
      its predictive validity at two stages in development (i.e., 1 and 3 years of
      age). METHOD: Twenty-three healthy neonates (control group) and 51 high-risk
      neonates (high-risk group) were assessed at term and were followed
      longitudinally. At 1 and 3 years, subjects in both groups were evaluated in a
      blind fashion by a psychologist and a pediatric neurologist. RESULTS:
      Developmental delays became more apparent as high-risk newborns matured; the
      percentage of subjects with an abnormal Griffiths general quotient increased from
      1 year (13.7%) to 3 years (39%). Analysis revealed that a normal neonatal
      performance on the ENNAS in high-risk subjects accurately predicted a favorable
      outcome at 1 year and 3 years of age. Although an abnormal ENNAS was not
      consistently associated with a poor outcome, the positive predictive value
      improved markedly from 1 year to 3 years of age. CONCLUSION: The findings
      indicate that a normal neonatal neurobehavioral assessment is reassuring, as most
      of these children are free of neurodevelopmental sequelae at 3 years of age. For
      many persons, the ENNAS may provide early evidence of a pattern of brain injury
      that is manifested only as the child is challenged by more complex skill
      acquisition such as language, memory, and perceptual-motor tasks. The ability of
      this assessment to predict behavioral and academic skills at school age remains
      to be determined. Early identification of developmental deficits enables
      occupational therapists to direct infants to appropriate early intervention
      programs, thus optimizing their functional potential.

PMID- 7524325
TI  - Effect of endoscopic white light on the developing visual pathway: a histologic,
      histochemical, and behavioral study.
AB  - OBJECTIVE: We examined the potential teratogenic effect of endoscopic white light
      on the developing visual pathways. STUDY DESIGN: The right eye of chicken embryos
      (n = 22) was exposed to maximal endoscopic light intensity on day 10 of
      development. At day 17 of development the histologic characteristics of the light
      exposed retinas were compared with those of the control embryos (n = 4). Normal
      functioning of the light-exposed eye was assessed by intravitreal injection of
      wheat germ agglutinin-horseradish peroxidase and observation of its axonal
      transport pattern to the diencephalic and mesencephalic visual centers. Axonal
      transport patterns were compared with those found in previous studies of normal
      embryos. Behavioral feeding patterns were compared between two groups of newly
      hatched chickens, one exposed to endoscopic light after hatching (n = 13) and the
      other, an unexposed control group (n = 12). RESULTS: No evidence of retinal
      damage, altered axonal transport or altered feeding patterns could be found
      between control and experimental animals. CONCLUSION: Endoscopic white light does
      not appear to be harmful to the developing retina and visual pathway.

PMID- 7524329
TI  - An immunohistochemical study of tissue transglutaminase in gliomas with reference
      to their cell dying processes.
AB  - Tissue transglutaminase is a Ca(2+)-dependent enzyme that catalyzes the formation
      of protein cross-links by an acyl transfer reaction. Recent reports have
      suggested that tissue transglutaminase is induced by tumor progression and
      apoptosis. In this study we immunohistochemically investigated a series of
      gliomas by using an antiserum against a dodecapeptide from the COOH-terminal of
      tissue transglutaminase. Among the gliomas the presence of positive
      immunoreactivity tended to increase in malignant counterparts. It is also
      noteworthy to mention that glioblastoma cells surrounding the zonal necrosis in a
      palisade fashion were strongly immunolabeled. The degenerating products in tumor
      cells, such as round granulated bodies, were primarily immunopositive, whereas
      Rosenthal fibers were negative. Dying cells through apoptosis in the metastatic
      brain tumors could be easily recognized by the presence of tissue
      transglutaminase. In conclusion, tissue transglutaminase may therefore be
      valuable in the prognostic characterization of gliomas with respect to the
      detection of dying cells. However, the appearance of tissue transglutaminase
      positive neoplastic cells was not limited to apoptotic bodies but could also be
      detected in necrobiotic cell nests.

PMID- 7524332
TI  - Expression of developmentally regulated muscle proteins in rhabdomyosarcomas.
AB  - Human skeletal muscle differentiation and maturation follows a precise sequence
      of events. To investigate whether and to what extent rhabdomyosarcoma (RMS) cells
      follow a comparable sequence, 29 fresh frozen specimens of RMS (14 primary and 15
      relapses) were immunostained with antibodies directed against developmentally
      regulated myosin heavy chains (MHC), ie, fetal, fast, and slow MHC, in addition
      to desmin and vimentin. Four distinct patterns of expression were observed: I)
      RMS cells expressing exclusively vimentin and desmin (n = 7), II) in addition to
      expression of vimentin and desmin, a minority of neoplastic cells were
      immunoreactive with fetal MHC (n = 6), III) in addition to pattern II, fast MHC
      was expressed (n = 7), and IV) RMS cells simultaneously expressing vimentin,
      desmin, fetal, fast, and slow MHC (n = 9). Accordingly, the proportion of the MHC
      immunoreactive RMS cells increased gradually along with the four patterns of
      expression evolving from less than 25% up to 75% for fetal MHC, from less than
      25% up to 50% for fast MHC, and up to 25% for slow MHC in the last category.
      Vimentin and desmin were coexpressed by almost all RMS cells. Double
      immunostaining revealed that comparable with the myogenic cells in the developing
      fetal skeletal muscle, expression of fetal MHC could be demonstrated in the same
      neoplastic cells either in conjunction with fast or slow MHC. In contrast, only
      in RMS, slow MHC expression in conjunction with fast MHC could be observed in the
      neoplastic cells. Neither the shape or size of neoplastic RMS cells, nor the
      histopathological types, nor tumor localization were related to the expression
      pattern of developmentally regulated MHC (fetal, fast, and slow MHC). These
      results confirm the commitment of the RMS cells to the myogenic pathway and
      demonstrate a restricted and aberrant differentiation pattern of the neoplastic
      cells in RMS compared with normal myogenesis, independent of histopathological
      types of RMS.

PMID- 7524330
TI  - Cell type-specific deficiency of c-kit gene expression in mutant mice of mi/mi
      genotype.
AB  - The mi locus of mice encodes a novel member of the basic-helix-loop-helix-leucine
      zipper protein family of transcription factors (hereafter called mi factor). In
      addition to microphthalmus, osteopetrosis, and lack of melanocytes, mice of mi/mi
      genotype are deficient in mast cells. Since the c-kit receptor tyrosine kinase
      plays an important role in the development of mast cells, and since the c-kit
      expression by cultured mast cells from mi/mi mice is deficient in both mRNA and
      protein levels, the mast cell deficiency of mi/mi mice has been attributed at
      least in part to the deficient expression of c-kit. However, it remained to be
      examined whether the c-kit expression was also deficient in tissues of mi/mi
      mice. In the present study, we examined the c-kit expression by mi/mi skin mast
      cells using in situ hybridization and immunohistochemistry. Moreover, we examined
      the c-kit expression by various cells other than mast cells in tissues of mi/mi
      mice. We found that the c-kit expression was deficient in mast cells but not in
      erythroid precursors, testicular germ cells, and neurons of mi/mi mice. This
      suggested that the regulation of the c-kit transcription by the mi factor was
      dependent on cell types. Mice of mi/mi genotype appeared to be a useful model to
      analyze the function of transcription factors in the whole-animal level.

PMID- 7524331
TI  - Angiogenesis in human coronary atherosclerotic plaques.
AB  - Neovascularization in the walls of coronary arteries is associated with the
      presence of atherosclerotic plaque. The mechanisms responsible for the formation
      of these intraplaque microvessels are not understood. The purpose of this study
      is to examine the prevalence of endothelial cell replication in plaque
      microvessels. Two hundred and one primary and restenotic coronary atherectomy
      specimens were analyzed for the presence of microvessels and proliferation as
      reflected by positive immunolabeling for Ulex agglutinin and the proliferating
      cell nuclear antigen, respectively. In primary but not restenotic specimens,
      proliferation of any cell type was associated with the detection of microvessels
      on the same slide. However, intraplaque microvessels were more commonly found in
      restenotic compared to primary specimens (P = 0.004). Twelve highly vascularized
      specimens with evidence of replication were subjected to detailed
      histomorphological and quantitative image analyses. At 200 x, the most vascular
      optical field of each slide was identified and consistently included plaque
      macrophages. Total slide endothelial cell replication indices for these specimens
      varied, but in some instances were remarkably elevated (eg, 43.5%). The role of
      intraplaque angiogenesis may be analogous to that of tumor or wound angiogenesis
      and be important in development and progression of coronary artery lesions and
      restenosis.

PMID- 7524333
TI  - Shear stress inhibits adhesion of cultured mouse endothelial cells to lymphocytes
      by downregulating VCAM-1 expression.
AB  - Monolayers of endothelial cells (EC) cultured from mouse lymph nodes were exposed
      to controlled levels of shear stress (0-7.1 dyn/cm2) in a parallel plate flow
      chamber, and binding between the flow-loaded EC and mouse lymph node-derived
      lymphocytes was assayed. A large number of lymphocytes adhered to the stationary
      control EC, but in EC exposed to a shear stress of 1.5 dyn/cm2 for 6 h, the
      adhesion decreased to 68.8 +/- 12.8% (SD; n = 19) of control (n = 29, P < 0.001).
      The decrease in adhesion induced by flow loading was time and shear stress
      dependent and reversible. Treatment of stationary EC with a monoclonal antibody
      (MAb) to vascular cell adhesion molecule-1 (VCAM-1) reduced the adhesion to 70.6
      +/- 11.5% (n = 19) of control (P < 0.001), whereas MAb to CD44 and to
      intercellular adhesion molecule-1 had no effect on it. Flow cytometric analysis
      revealed that the amount of VCAM-1 expressed on the cell surface was decreased to
      48.5 +/- 15.8% (n = 6) of control by flow loading (P < 0.001). Flow loading
      experiments using two perfusates with different viscosities demonstrated that the
      decrease in VCAM-1 expression due to flow was shear stress rather than shear rate
      dependent. The detection of mRNA by reverse transcriptase-polymerase chain
      reaction showed that VCAM-1 mRNA levels were markedly depressed in EC exposed to
      flow loading.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524334
TI  - Polyamine deficiency causes reorganization of F-actin and tropomyosin in IEC-6
      cells.
AB  - In earlier work we have shown that polyamine-deficient IEC-6 cells lose most of
      their ability to migrate. In this report we describe the effect of polyamine
      deficiency on the cytoskeleton of migrating IEC-6 cells. Cells were grown on
      cover slips for 4 days. One-third of the monolayer was removed, and the remainder
      was incubated for 6 h. The monolayers were fixed and stained with rhodamine
      phalloidin for actin filaments and by immunocytochemistry for tropomyosin. In
      control cells, actin filaments were found as stress fibers traversing the cell,
      in a thin actin cortex often visible on only one edge of the cell, and in fine
      fibers extending into the lamellipodia. Tropomyosin was found in the same
      distribution. A Western blot showed that tropomyosin was present as 35- and 37
      kDa isoforms. In polyamine-deficient cells, actin stress fibers were less dense,
      whereas the actin cortex was greatly increased in density and lamellipodia were
      less extensive. Tropomyosin distribution was similar and included a 30-kDa
      isoform not seen previously. In spite of the obvious changes in the distribution
      of these cytoskeletal proteins, the concentrations of filamentous actin, beta
      actin mRNA, and the higher molecular weight tropomyosin isoforms did not change.
      In all cases the addition of putrescine to polyamine-deficient cells prevented
      the changes described. We conclude that polyamines are essential for migration in
      this system because of their effects on the organization of cytoskeletal actin,
      tropomyosin, and perhaps other proteins as well.

PMID- 7524335
TI  - cAMP and inositol 1,4,5-trisphosphate increase Ca2+ in HT-29 cells by activating
      different Ca2+ influx pathways.
AB  - Ca2+ plays a central role in regulating transepithelial fluid and electrolyte
      transport in intestinal epithelial cells. To investigate the mechanisms
      regulating the cytosolic free Ca2+ concentration ([Ca2+]c), we examined the
      effect of secretory agonists on [Ca2+]c in the intestinal epithelial cell line HT
      29 clone 19A cells. We found that [Ca2+]c increased after addition of either
      adenosine 3',5'-cyclic monophosphate (cAMP)-dependent agonists or a D-myo
      inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]dependent agonist carbachol. Several
      lines of evidence suggest that cAMP- and Ins(1,4,5)P3-dependent agonists act
      through separate pathways. First, isoproterenol and forskolin increased cellular
      levels of cAMP but not Ins(1,4,5)P3, whereas carbachol increased cellular levels
      of Ins(1,4,5)P3 and stimulated inositol phosphate turnover without increasing
      cAMP. Second, carbachol increased [Ca2+]c by stimulating the release of Ca2+ from
      intracellular stores and influx of extracellular Ca2+. In contrast, cAMP agonists
      increased [Ca2+]c by stimulating Ca2+ influx alone. Third, the responses to
      maximal concentrations of cAMP agonists and carbachol were approximately
      additive. Finally, Ins(1,4,5)P3- but not cAMP agonist-dependent Ca2+ influx was
      inhibited by inorganic Ca2+ channel blockers. Thus, in intestinal epithelial
      cells, [Ca2+]c is regulated by at least two different second-messenger pathways,
      involving Ins(1,4,5)P3 or cAMP. In addition, cAMP stimulates influx of
      extracellular Ca2+ through a pathway distinct from that mediated by Ins(1,4,5)P3.

PMID- 7524336
TI  - A basolateral CHIP28/MIP26-related protein (BLIP) in kidney principal cells and
      gastric parietal cells.
AB  - The water channel CHIP28 accounts for the high water permeability of proximal
      tubules and thin descending limbs of Henle; a homologous water channel, WCH-CD,
      in the apical membrane of collecting duct principal cells, may be the vasopressin
      sensitive water channel. We show here that one antiserum, raised against CHIP28,
      immunostains the basolateral membrane of collecting duct principal cells, in
      addition to staining CHIP28 in other cells. This serum was named anti-basolateral
      integral protein (anti-BLIP) to distinguish it from other anti-CHIP28 antisera.
      By Western blotting, BLIP serum recognized both CHIP28 and MIP26, and it stained
      lens fibers, which contain MIP26 but not CHIP28. BLIP antiserum
      immunoprecipitated a 28-kDa band, a broad 35- to 50-kDa band, and an
      approximately 16-kDa band from kidney papilla. It also stained the basolateral
      membrane of gastric parietal cells, which were not stained with anti-CHIP28 or
      anti-MIP26 antibodies. BLIP antiserum immunoprecipitated a 28-kDa protein band
      from stomach; this protein was not precipitated by anti-CHIP28 antibodies. These
      results suggest that basolateral membranes of principal cells and parietal cells
      contain a protein(s) that shares common epitopes with CHIP28 and MIP26. Finally,
      BLIP but not CHIP28 antiserum stained mesothelial (but not epithelial) cells of
      toad urinary bladder, a further indication that the BLIP antiserum recognizes a
      protein distinct from CHIP28.

PMID- 7524337
TI  - Anti-idiotypic antibodies to delineate epitope specificity of anti-amiloride
      antibodies.
AB  - Amiloride and related compounds have found widespread use as cation transport
      inhibitors. We have previously raised a series of polyclonal anti-amiloride
      antibodies using different amiloride-protein conjugates as immunogens, where
      amiloride was coupled to protein either through its guanidino moiety or through
      its 5-aminopyrazinyl moiety. The anti-amiloride antibodies recognized distinct
      sites on amiloride, and the site of attachment of amiloride to carrier protein
      was a critical factor in determining which part of the amiloride molecule was
      recognized by the anti-amiloride antibody. The specificity of binding of
      amiloride analogues to these polyclonal anti-amiloride antibodies mimicked the
      specificity of binding of amiloride analogues to selected isoforms of the
      epithelial Na+ channel or the Na+/H+ exchanger, suggesting that antigen binding
      site of these antibodies might be similar in structure to amiloride binding sites
      on selected Na+ transport proteins. We previously generated monoclonal anti
      idiotypic antibodies RA2.4 and RA6.3 by an auto-anti-idiotypic approach, using
      amiloride coupled to albumin through the guanidinium moiety (amiloride-A1). We
      have now raised a series of monoclonal anti-idiotypic antibodies, T6, T26, T40,
      and T181, using amiloride coupled to keyhole limpet hemocyanin through the 5
      aminopyrazinyl moiety (amiloride-A5) as an immunogen with the same auto-anti
      idiotypic approach. These monoclonal anti-idiotypic antibodies recognized both
      polyclonal anti-amiloride-A1 and anti-amiloride-A5 antibodies, suggesting that
      idiotype-anti-idiotype interaction was not epitope restricted.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7524338
TI  - pHi and serum regulate AE2-mediated Cl-/HCO3- exchange in CHOP cells of defined
      transient transfection status.
AB  - Anion exchanger (AE) protein-mediated anion exchange contributes to regulation of
      intracellular pH (pHi), Cl- concentration, and volume in vertebrate cells. We
      have extended the functional characterization of recombinant AE2-mediated Cl
      /HCO3- exchange in single Chinese hamster ovary cells stably transfected with the
      polyoma large T antigen (CHOP cells) of defined transient transfection status
      using a novel surface marker coexpression vector. Marker expression and detection
      had minimal effect on the low endogenous Cl-/HCO3- exchange activity of CHOP
      cells, whereas coexpression of marker with AE2 elevated CHOP cell Cl-/HCO3-
      exchange activity 16-fold. Between pHi of 7.3 and 7.8, AE2-mediated flux of
      proton equivalents was activated > 11-fold by increasingly alkaline pHi without
      reaching saturation. This activation may be secondary to allosteric effects of
      pHi on AE2, in parallel with the obligatory increase in substrate intracellular
      HCO3- concentration. Nominal removal of CO2/HCO3- reduced AE2 activity by 90%.
      Addition of 10% calf serum slowly activated AE2 activity severalfold. This
      activation was slowly reversed after serum removal. Surface marker coexpression
      vectors improve both the efficiency and reliability of studies of recombinant
      protein function for a wide range of single cell assays in many cell types.

PMID- 7524339
TI  - IGF-I and IGF-binding protein gene expressions in spontaneous dwarf rat.
AB  - Effects of growth hormone (GH) and fasting on hepatic expressions of insulin-like
      growth factor I (IGF-I) and IGF-I-binding protein (IGFBP)-1, -2, -3, and -4 were
      examined in spontaneous dwarf rats (SDR), which completely and specifically lack
      GH among pituitary hormones. The hepatic expressions of mRNA encoding IGF-I and
      IGFBP-3 were reduced and IGFBP-1 mRNA was elevated in the SDR. Both chronic and
      acute administration of GH restored these changes, indicating the association of
      GH but not other pituitary hormones with hepatic expressions of these genes. In
      addition, the present examination revealed that mRNA level of IGFBP-2 was
      elevated in SDR, which could not be attenuated by exogenous GH, and that GH may
      not be directly relevant to the regulation of hepatic IGFBP-4 expression. Fasting
      for 2 days reduced IGF-I mRNA level and increased IGFBP-2 mRNA level in the SDR,
      as well as in the normal rat, suggesting the presence of factors other than
      reduced serum GH responsible for fasting-induced alteration in the expression of
      these mRNAs. On the other hand, fasting resulted in little change or even a
      reduction of IGFBP-1 mRNA level in the SDR.

PMID- 7524340
TI  - Effects of substance P on adrenal responses to acetylcholine in conscious calves.
AB  - The effect of intra-aortic infusions of substance P (SP; 10 or 20 pmol.min-1.kg
      1) on adrenal responses to acetylcholine (4.5 nmol.min-1.kg-1 ia) have been
      investigated in functionally hypophysectomized calves given exogenous
      adrenocorticotropic hormone (0.7 pmol.min-1.kg-1). At the lower dose, SP had no
      effect on cortisol output. In contrast, SP inhibited the output of both
      catecholamines and enkephalins in response to acetylcholine, without affecting
      the output of corticotropin-releasing factor (CRF). Increasing the dose of SP to
      20 pmol.min-1.kg-1 ia significantly reduced the outputs of both cortisol and CRF
      (P < 0.025 and 0.01 respectively). It is concluded that SP is capable of
      modulating both adrenal cortical and medullary responses to acetylcholine and
      that the latter are more sensitive to this influence than the former.

PMID- 7524341
TI  - Effect of a Rab3A effector domain-related peptide, CCK, and EGF in permeabilized
      pancreatic acini.
AB  - We report here that a synthetic peptide of the effector domain of the small
      molecular-weight GTP-binding protein Rab3A (EDRab3AL) is a potent stimulator of
      inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] production and amylase secretion in
      digitonin-permeabilized pancreatic acini. Moreover, the Rab3A effector domain
      peptide caused phosphatidylinositol 4,5-bisphosphate breakdown, indicating that
      the observed increase in Ins(1,4,5)P3 is due to stimulation of a phosphoinositide
      specific phospholipase C (PLC). The dose-response curve for EDRab3AL-induced
      amylase release was biphasic, showing a maximum at 0.3 nM EDRab3AL and a decline
      at higher peptide concentrations. By contrast, the dose-response curve for
      EDRab3AL-induced Ins(1,4,5)P3 production was monophasic, showing stimulation with
      increasing EDRab3AL concentrations. A peptide of the effector domain of Rab1A,
      EDRab1AL, had no effect, indicating that the response to EDRab3AL is specific.
      Cholecystokinin octapeptide (CCK-8) and EDRab3AL had additive effects on the
      acinar Ins(1,4,5)P3 level. Epidermal growth factor (EGF), which has recently been
      shown to inhibit CCK-8-induced Ins(1,4,5)P3 production in pancreatic acinar
      cells, also decreased EDRab3AL-induced Ins(1,4,5)P3 production. These results
      suggest that EDRab3AL and CCK-8 act on the same EGF-inhibitable PLC by
      independent mechanisms. CCK-8 increased and EGF decreased amylase release in
      response to submaximal EDRab3AL concentrations. By contrast, at supramaximal
      EDRab3AL concentrations EGF increased and CCK-8 decreased EDRab3AL-stimulated
      amylase release. EDRab3AL had no effect in intact acini, indicating that the site
      of action of EDRab3AL is intracellular. We conclude that EDRab3AL regulates
      phosphoinositide-specific PLC activity and thereby amylase secretion in an
      analogous fashion to CCK-8, but from within the cell.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7524343
TI  - Voltage-activated potassium currents of rabbit osteoclasts: effects of
      extracellular calcium.
AB  - The effects of increased extracellular Ca2+ concentration ([Ca2+]e) were examined
      on a delayed-rectifier K+ current (IK) and an inward-rectifier K+ current (IK1)
      in rabbit osteoclasts. Elevation of [Ca2+]e from 1.8 to 18 mM shifted the half
      point for IK activation by +11.5 mV and the voltage dependence of inactivation by
      +9.7 mV and slowed the rate of IK activation and deactivation. These effects of
      elevated [Ca2+]e on IK are consistent with screening of cell surface negative
      charge. However, elevation of [Ca2+]e increased the voltage-dependent kinetics of
      IK inactivation at all potentials tested, inconsistent with that predicted by
      simple surface charge theory. This finding suggests an additional, regulatory
      role for [Ca2+]e in the gating of IK channels. Some osteoclasts had an IK1, which
      was decreased when [Ca2+]e was raised from 1.8 to 18 mM. The physiological
      function of both types of K+ currents remains to be determined, and it is not
      clear whether these currents are involved with the coupling of cytosolic [Ca2+]
      to [Ca2+]e.

PMID- 7524344
TI  - Responses to extracellular ATP of lymphoblastoid cell lines from Duchenne
      muscular dystrophy patients.
AB  - We have observed a striking difference in the response to extracellular ATP in
      lymphoblastoid cell lines established from Duchenne muscular dystrophy patients
      and normal subjects. Duchenne muscular dystrophy cells stimulated by
      extracellular ATP underwent a large increase in the cytoplasmic Ca2+
      concentration ([Ca2+]i) and plasma membrane depolarization, while normal cell
      lines were little or not at all responsive. These changes in intracellular ion
      homeostasis were due to activation of an ATP-gated membrane channel permeable to
      Na+ and Ca2+, with little or no contribution of Ca2+ release from intracellular
      stores. The channel was selectively activated by ATP, since other
      purine/pyrimidine nucleotides were ineffective, and it was inhibited by
      pretreatment with oxidized ATP, a compound previously reported to irreversibly
      inhibit P2 purinergic receptors. In the presence of extracellular ATP,
      lymphoblastoid cells established from Duchenne muscular dystrophy patients, but
      not from healthy controls, underwent rounding and swelling and eventually lysed.
      The results of this study suggest that lymphoblastoid cells isolated from
      Duchenne muscular dystrophy patients are eminently sensitive to stimulation by
      extracellular ATP.

PMID- 7524342
TI  - Immortalization of subpopulations of respiratory epithelial cells from transgenic
      mice bearing SV40 large T antigen.
AB  - Murine lung epithelial (MLE) cell lines were produced from lung tumors derived
      from transgenic mice bearing the viral oncogene, SV40 large T antigen, under
      transcriptional control of the promoter-enhancer region of the human surfactant
      protein C (SP-C) gene. Cells were selected on the basis of increased murine
      cystic fibrosis transmembrane conductance regulator (mCFTR) mRNA content and were
      dilution cloned to produce distinct immortalized epithelial cell lines. MLE-13a3
      cell lines expressing high levels of mCFTR mRNA also expressed apolipoprotein J
      (apoJ) mRNA, a developmentally regulated glycoprotein expressed preferentially in
      fetal lung. SP-A, -B, and -C were not detected or were present at low levels in
      the MLE cells that contained abundant CFTR and apoJ mRNA. In contrast, MLE cells,
      cloned on the basis of abundant surfactant protein mRNAs, expressed apoJ and
      mCFTR mRNAs at low levels. Forskolin-stimulated short-circuit current, typical of
      CFTR-mediated chloride transport activity, was generated by monolayers of
      subclones of the MLE-13a3 cell lines. Tumor necrosis factor-alpha stimulated
      mCFTR mRNA, whereas dexamethasone, retinoic acid, and phorbol ester had no effect
      on the levels of mCFTR mRNA in MLE-13a3 cells.

PMID- 7524345
TI  - Salt stress increases abundance and glycosylation of CFTR localized at apical
      surfaces of salt gland secretory cells.
AB  - Osmotic stress elicits hypertonic NaCl secretion and promotes structural and
      biochemical differentiation in avian salt glands. In addition to cholinergic
      control, Cl- secretion is stimulated by vasoactive intestinal peptide (VIP),
      suggesting that the cystic fibrosis transmembrane conductance regulator (CFTR)
      may be present and that its expression may be regulated by chronic salt stress.
      Anion efflux, assayed by 6-methoxy-N-(3-sulfopropyl)quinolinium fluorescence
      changes in single cells, was stimulated by VIP or 8-(4-chlorophenylthio)adenosine
      3',5'-cyclic monophosphate. Immunoblots with a COOH-terminal peptide antibody to
      human CFTR revealed approximately 170- and approximately 180-kDa bands in lysates
      from control and salt-stressed glands, respectively. Both variants reduced to
      approximately 140 kDa after N-glycanase digestion and gave identical tryptic
      phosphopeptide maps after immunoprecipitation and phosphorylation by protein
      kinase A. CFTR was localized to apical membranes by immunofluorescence and,
      additionally, to subapical vesicles by immunoelectron microscopy. Salt stress
      induced an approximately twofold increase in CFTR abundance/cell protein
      (approximately 5-fold/cell) and intensified apical membrane immunofluorescence.
      For comparison, Na+ pump expression increased approximately fourfold per cell
      protein with little change in actin. Thus differentiation induced by salt stress
      is accompanied by alteration in CFTR abundance and glycosylation. Upregulation of
      CFTR likely contributes to increased efficiency of Cl- secretion.

PMID- 7524346
TI  - Nitric oxide attenuates leukocyte-endothelial interaction via P-selectin in
      splanchnic ischemia-reperfusion.
AB  - We studied the effects of exogenous nitric oxide (NO) on leukocyte-endothelial
      interaction after 60 min of splanchnic artery ischemia and 120 min of reperfusion
      (SAO/R) in pentobarbital sodium-anesthetized rats via intravital microscopy.
      Treatment with the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 20
      micrograms/kg bolus followed by infusion at 20 micrograms.kg-1.h-1), beginning 10
      min before reperfusion, resulted in significantly decreased leukocyte-endothelial
      interaction. This was manifested by a significant decrease in leukocyte rolling
      and adherence in the postcapillary venules. Tissue protection was demonstrated by
      a significantly lower plasma free amino-nitrogen concentration in the SNAP
      treated SAO/R rats compared with those receiving NO-depleted SNAP (P < 0.05).
      Immunohistochemical localization of P-selectin showed significantly decreased P
      selectin expression on the venular endothelium after SAO/R in rats given SNAP 10
      min before reperfusion (23.0 +/- 3.2% vs. 54.9 +/- 12.1% positive staining,
      respectively, P < 0.01). From these data, we conclude that the effects of
      exogenous NO on leukocyte-endothelial interaction after ischemia-reperfusion
      appear to be at least partially mediated through the endothelial adhesion
      molecule P-selectin.

PMID- 7524349
TI  - Corelease of neuropeptides from capsaicin-sensitive afferents dilates submucosal
      arterioles in guinea pig ileum.
AB  - Extrinsic sensory afferent nerves projecting to the guinea pig intestinal
      submucosal arterioles contain both substance P (SP) and calcitonin gene-related
      peptide (CGRP); selective stimulation of these nerves causes vasodilation.
      However, it is not known whether either or both of these neuropeptides may be
      responsible for this neurogenic vasodilation. To examine this question, the
      actions of selective SP and CGRP antagonists on vasodilations evoked by SP, CGRP,
      and selective stimulation of extrinsic sensory afferents with capsaicin were
      measured in isolated submucosal arteriolar preparations with videomicroscopy. The
      SP receptor antagonist CP-96,345 (200 nM) abolished the vasodilation produced by
      half-maximal concentration (EC50) of SP and was without effect on the
      vasodilation produced by EC50 concentration of CGRP. Conversely, the CGRP
      receptor antagonist, CGRP-(8--37) (1 microM) abolished the vasodilation to CGRP
      but did not alter the SP-induced vasodilation. Neither antagonist altered the
      muscarinic vasodilation or nerve-evoked sympathetic vasoconstriction. Maximum
      inhibition of the capsaicin-induced vasodilation by CP-96,345 (600 nM) was 67%,
      and maximum inhibition of this response by CGRP-(8--37) (2 microM) was 53%.
      Complete inhibition of the capsaicin-induced vasodilation occurred when both
      antagonists were present. It is concluded that the vasodilation in response to
      activation of extrinsic sensory afferents innervating submucosal arterioles is
      due to the corelease of SP and CGRP.

PMID- 7524347
TI  - Regulation of pancreatic amylase and lipase gene expression by diet and insulin
      in diabetic rats.
AB  - Although insulin has been proposed to mediate the dietary regulation of
      pancreatic amylase, its interaction with diet in the regulation of amylase and
      lipase is not well understood and was examined in diabetic rats fed diets high in
      carbohydrate (HC), protein (HP), or fat (HF) and treated with insulin. Diabetes,
      independent of diet, decreased amylase content (97%; P < 0.0001) and mRNA (90%; P
      < 0.0001), but insulin only restored amylase content and mRNA to respective
      dietary control values. Diabetes, independent of diet, also increased lipase mRNA
      1.6-fold (P < 0.004) but interacted (P < 0.0003) with diet on lipase content,
      resulting in opposite effects in HC- (increased 202%) and HF-diabetic rats
      (decreased 40%). Insulin partially restored lipase content and mRNA to respective
      dietary control values. Diet, independent of diabetes, regulated amylase content
      (P < 0.0001) and mRNA (P < 0.0003), which were three- to fourfold greater in HC-
      than in HF-fed rats, and lipase content (P < 0.001) and mRNA [rat pancreatic
      lipase 1 (rPL-1), P < 0.04; rPL-3, P < 0.0001], which were 1.8-fold greater in HF
      than in HC- or HP-fed rats. Insulin failed to stimulate maximal amylase gene
      expression in HP- or HF-fed diabetic rats, suggesting that it is necessary, but
      not sufficient, for this dietary regulation. Differential regulation of lipase
      activity and mRNA by diet and insulin raises the possibility that lipase gene
      expression is regulated by a complex interaction of diet and insulin.

PMID- 7524348
TI  - Expression of IGF-II and IGF-binding proteins by colon cancer cells in relation
      to growth response to IGFs.
AB  - We previously reported that even though virtually all human colon cancers were
      positive for IGF-I receptors, only 50% responded to growth effects of insulin
      like growth factor (IGF)-I (1-100 nM). The present studies were undertaken to
      determine whether expression and secretion of IGFs (IGF-I, IGF-II) and IGF
      binding proteins (BPs; 1-6) were perhaps different in IGF-responsive (COLO 205,
      COLO 320, Caco-2) and IGF-nonresponsive (HCT 116, HT-29, DLD-1) cells. Several
      bands (2.0-6.0 kb) of IGF-II mRNA transcripts were detected in all the cell
      lines; none expressed IGF-I. Significant concentrations of IGF-II (0.2-0.9
      ng/10(6) cells) were measured in the conditioned media (CM) of the cells. All
      cell lines expressed BP2 and/or BP4 mRNA and secreted BP4 (24 kDa) and/or BP2
      (32.5 kDa); BP1 was not detected in any cell line. Interestingly, BP3 mRNA was
      measured only in the responsive cell lines. The relative concentration of total
      BPs tended to be higher in the CM of nonresponsive cells. Interestingly, a large
      concentration of 44- to 48-kDa BP (BP3?) was associated with the membranes of
      only the responsive cell lines. Our present studies thus demonstrate that human
      colon cancers do not secrete IGF-I and BP1. Of all the IGF-related factors
      examined, the quantity and the type of BPs expressed by the human colon cancer
      cell lines (especially BP2, BP4, and BP3) may significantly dictate the growth
      response of the cells to exogenous IGF-I.

PMID- 7524351
TI  - Intestinal anaphylaxis: radiation-induced suppression.
AB  - The gastrointestinal tract is highly sensitive to ionizing radiation. Some of the
      most radiosensitive cells in this system are mast cells and epithelium. This
      article describes experiments that test the hypothesis that irradiation
      suppresses mucosal immune responses in which mast cells and epithelium are
      involved. The hypothesis was tested by examining the impact of ionizing radiation
      on anaphylactically mediated Cl- secretion in jejunum of rats sensitized by
      Trichinella spiralis infection and challenged with antigen derived from the
      parasite. Antigen-induced Cl- secretion was measured electrophysiologically in
      vitro. Rats were immunized by inoculation with 3 x 10(3) T. spiralis larvae and,
      30-50 days later, exposed to total abdominal irradiation from a cobalt-60 gamma
      source. Doses were 5, 7, and 9 Gy. At 1, 3, 5, 7, 14, and 21 days postirradiation
      (DPI), jejunal segments were assessed for immune responsiveness. (Duration of
      suppression to antigenic challenge was directly related to radiation dose).
      Recovery of response to antigenic challenge after irradiation with 5 Gy was
      complete by 5 DPI. At 7 Gy, responsiveness was totally suppressed from 1 to 5
      DPI, was partially expressed from 5 to 14 DPI, and was completely restored by 21
      DPI. A dose of 9 Gy completely suppressed immune responsiveness throughout the 21
      day period. Full responsiveness of jejunum to exogenous Cl- secretagogues at 1-5
      DPI indicates that the immunosuppressive effect of radiation was not due to a
      breakdown in the secretory process at the epithelium level.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7524352
TI  - Ontogeny of surfactant proteins and lipid-synthesizing enzymes in cultured fetal
      lung epithelial cells.
AB  - Fetal rat lung epithelial cells were isolated on gestational day 17 (term is 22),
      separated from fibroblasts, and cultured up to 6 days in a serum-free medium on a
      basement membrane matrix. Surfactant protein (SP) A, barely detectable by
      immunostaining at the beginning of the culture, considerably increased in cells
      and subsequently in the lumen of the epithelial cell clusters. SP-A mRNA, already
      detectable at culture initiation, progressively increased. By contrast, SP-B and
      its mRNA appeared after 2-3 days. SP-C mRNA appeared only after 4 days of
      culture. Cells cultured 6 days had a phospholipid composition similar to that of
      freshly isolated adult rat type II cells. The enhancement of lipid synthesis
      between the first and the sixth culture days, reported earlier to occur in these
      cells, was found to be accompanied by a two- to fivefold increase in amount of
      mRNAs of lipogenic enzymes and choline phosphate cytidylyltransferase. In
      conclusion, alveolar epithelial type II cells appear to be capable of full
      differentiation in vitro, and components of the surfactant system are all
      regulated developmentally at a pretranslational level.

PMID- 7524354
TI  - Isolation, culture, and characterization of rat lung microvascular endothelial
      cells.
AB  - Highly pure primary cultures of rat lung microvascular endothelial cells were
      obtained from peripheral lung tissue using a combination of selective culture
      strategies. The cells had a characteristic morphology consistent with an
      endothelial origin and were positive for a number of endothelial cell markers,
      including uptake of fluorescent acetylated lactate dehydrogenase, binding of the
      lectin Bandeiraea simplicifolia I, and positive immunofluorescence staining with
      two endothelial cell monoclonal antibodies. The cells behaved as microvascular
      endothelial cells using an in vitro angiogenesis assay. This isolation method
      provides a simple method for culturing the pulmonary microvasculature of the rat
      and these studies support the idea that endothelial cells from different vessels
      exhibit phenotypic heterogeneity. This method should prove useful for studying
      specialized endothelial cell function and differentiation in vitro.

PMID- 7524353
TI  - Selective differences in vascular endothelial- vs. airway epithelial-T cell
      adhesion mechanisms.
AB  - The basis for T cell adhesion to airway epithelial and vascular endothelial cells
      was studied using a quantitative flow cytometry-based assay that avoids extensive
      leukocyte purification and labeling. Compared with standard cell-labeling
      methods, the flow cytometry-based assay yielded a lower level of constitutive T
      cell adhesion, despite a similar level of stimulated adhesion (after T cell
      activation with phorbol dibutyrate) using endothelial or epithelial cell
      monolayers. Endothelial T cell adhesion was further increased by monolayer
      treatment with tumor necrosis factor-alpha (less so with interleukin-1 beta and
      least with interferon-gamma), whereas epithelial T cell adhesion was most
      sensitive to interferon-gamma. Cytokine stimulation of adhesion was invariably
      concentration dependent and closely matched to the cellular levels of
      intracellular adhesion molecule-1 (ICAM-1). Accordingly, stimulated T cell
      adhesion was markedly inhibited by anti-ICAM-1 or anti-beta 2-integrin antibody
      (95-97% inhibition for epithelial cells and 57-67% inhibition for endothelial
      cells) directed against ICAM-1 interaction with lymphocyte function-associated
      antigen-1 (LFA-1; alpha L beta 2-integrin). Residual endothelial T cell adhesion
      that correlated with endothelial vascular cell adhesion molecule-1 (VCAM-1)
      levels was blocked by an anti-alpha 4-integrin antibody directed against VCAM-1
      interaction with very late activation antigen-4 (VLA-4; alpha 4 beta 1-integrin).
      The results suggest that 1) peripheral blood T cells without exogenous activation
      exhibit little LFA-1- or VLA-4-dependent adherence except to endothelial or
      epithelial cells expressing high levels of ICAM-1 and/or VCAM-1; and 2)
      differences in endothelial vs. epithelial cell mechanisms to bind activated and
      unactivated T cells (e.g., dependence on a mixed- vs. a single-ligand system and
      distinct cytokine-responsiveness of ligand levels) may help to coordinate T cell
      traffic to epithelial barriers.

PMID- 7524355
TI  - Nitric oxide inhibits bafilomycin-sensitive H(+)-ATPase activity in rat cortical
      collecting duct.
AB  - Nitric oxide (NO) is a messenger molecule that is produced from L-arginine by NO
      synthase (NOS). Some NOS isoforms are present in cells constitutively, whereas
      others can be induced by cytokines. Recent evidence suggests that NO inhibits
      intracellular pH regulation by the vacuolar H(+)-adenosinetriphosphatase (ATPase)
      in macrophages, which contain an inducible form of NOS. The vacuolar H(+)-ATPase
      is involved in proton secretion in intercalated cells in the collecting duct. We
      have therefore examined the effect of NO on bafilomycin-sensitive H(+)-ATPase
      activity in individual cortical collecting ducts (CCD) microdissected from
      collagenase-treated kidneys of normal rats using a fluorometric microassay.
      Incubation of CCD with the NO donors, sodium nitroprusside (0.1 and 1 mM) or 3
      morpholino-sydnonimine hydrochloride (SIN-1, 30 microM), caused a dose-dependent
      decrease in H(+)-ATPase activity. Incubation of CCD with lipopolysaccharide (LPS)
      and interferon-gamma, which induces NOS in macrophages, decreased H(+)-ATPase
      activity by 85%. This effect was prevented by simultaneous incubation with N
      omega-nitro-L-arginine, a competitive inhibitor of NOS, indicating that the
      decrease in H(+)-ATPase activity was caused by NO production. Incubation with 8
      bromo-guanosine 3',5'-cyclic monophosphate (cGMP) also inhibited H(+)-ATPase
      activity, suggesting that NO may exert its effect in the CCD via activation of
      guanylyl cyclase and production of cGMP. Immunohistochemistry using antibodies to
      the macrophage-type NOS revealed strong labeling of intercalated cells in the
      CCD, confirming the presence of NOS in these cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7524350
TI  - Gastrin effects on isolated rat enterochromaffin-like cells in primary culture.
AB  - The hormone gastrin stimulates acid secretion by releasing histamine from gastric
      enterochromaffin-like (ECL) cells and induces ECL cell proliferation in vivo.
      This study uses a > 90% pure ECL cell preparation in culture to compare gastrin
      effects on histamine release, histidine decarboxylase (HDC) activity, and DNA
      synthesis. Gastrin and the cholecystokinin octapeptide (CCK-8, nonsulfated)
      induced histamine release from ECL cells (24-96 h of primary culture) within 5
      min of incubation [concentration eliciting 50% of maximal response (EC50), 4 and
      2 x 10(-11) M, respectively]. The CCK-B antagonist L-365,260 inhibited this
      effect [concentration inhibiting 50% of maximal response (IC50), 2 x 10(-8) M],
      whereas the CCK-A antagonist L-364,718 (10(-8) M) and the tyrosine kinase
      inhibitor genistein (10(-4) M) had no effect. Histamine release was associated
      with a biphasic elevation of intracellular Ca2+. Gastrin stimulated HDC activity
      two- to threefold after 60 min of incubation (EC50, 10(-10) M). Gastrin also
      increased DNA synthesis in ECL cells, with an EC50 of 1.7 x 10(-12) M as measured
      by the incorporation of 5-bromo-2'-deoxyuridine (BrdU). Positive nuclear
      immunostaining increased two- to threefold in up to 20% of ECL cells after 48-96
      h of incubation. This effect was inhibited by L-365,260 (IC50, 5 x 10(-9) M) and
      by genistein (10(-4) M) but was not altered by L-364,718 (10(-8) M). The
      antisecretory drugs omeprazole, lansoprazole, and pantoprazole did not affect
      BrdU incorporation in isolated ECL cells. In conclusion, acute and chronic
      gastrin effects on the ECL cell are mediated via CCK-B receptors but differ in
      apparent receptor affinity and signal transduction pathways.

PMID- 7524356
TI  - Mitogenic signaling of thrombin in mesangial cells: role of tyrosine
      phosphorylation.
AB  - Thrombin elicits multiple biological effects on a variety of cells. We have
      previously shown that thrombin is a potent mitogen for human glomerular mesangial
      cells. This mitogenic effect of thrombin is associated with activation of
      phospholipase C (PLC) and induction of platelet-derived growth factor (PDGF) gene
      expression. The thrombin receptor, which belongs to the guanine nucleotide
      binding protein (G protein)-coupled receptor family, has recently been shown to
      induce rapid tyrosine phosphorylation of cellular proteins. In the present study,
      we investigated the role of protein-tyrosine phosphorylation in mediating the
      cellular responses elicited by thrombin in human glomerular mesangial cells.
      Amino acid labeling followed by immunoprecipitation with phosphotyrosine
      antibodies demonstrate that thrombin stimulates tyrosine phosphorylation of a set
      of cellular proteins. Treatment of mesangial cells with thrombin followed by
      immunoblotting with phosphotyrosine antibodies showed three major bands of
      tyrosine-phosphorylated proteins approximately 130, 70, and 44-42 kDa.
      Phosphorylation of these proteins was inhibited by two tyrosine kinase
      inhibitors, herbimycin A and genistein. Both compounds inhibited DNA synthesis
      and PDGF B-chain gene expression but had no effect on inositol phosphates
      production or increases in cytosolic calcium in response to thrombin. These data
      demonstrate that protein-tyrosine phosphorylation is not required for thrombin
      induced PLC activation with inositol phosphate formation and subsequent
      intracellular calcium release, but it is an absolute requirement for thrombin
      induced DNA synthesis and PDGF B-chain gene expression.

PMID- 7524359
TI  - Inhibition of locally produced nitric oxide resets tubuloglomerular feedback
      mechanism.
AB  - This study was designed to compare the effects of systemic and intratubular
      infusions of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (L
      NNA) on the tubuloglomerular feedback (TGF) mechanism in anesthetized rats. We
      recently showed that intravenous infusion of L-NNA led to increases in mean
      arterial blood pressure (Pa), proximal tubular stop-flow pressure (Psf), and
      enhanced TGF sensitivity and reactivity. To avoid major systemic effects, in this
      study TGF was studied after intratubular NO inhibition. Intratubular infusion of
      L-NNA (10(-3) M) yielded similar results as shown with intravenous infusion,
      without systemic effects. TGF sensitivity and reactivity were increased,
      indicated by decreased turning point (TP) from 19.8 +/- 1.0 to 15.2 +/- 0.7
      nl/min and increased delta Psf from 10.0 +/- 0.8 to 23.9 +/- 1.9 mmHg (24.3 vs.
      59.1%). L-NNA at a concentration of 10(-4) M showed significant changes in both
      TP (from 20.9 +/- 1.1 to 17.8 +/- 1.0 nl/min) and delta Psf (from 7.6 +/- 0.6 to
      13.9 +/- 0.7 mmHg), whereas 10(-5) M only increased delta Psf (9.7 +/- 1.0 vs.
      12.1 +/- 1.1 mmHg). However, at low tubular perfusion rates Psf was not
      influenced by L-NNA. The early proximal flow rate (EPFR) showed no change at low
      tubular perfusion rates with L-NNA. At maximal TGF activation (40 nl/min), delta
      EPFR was increased from 34% in control to 62%. Our results suggest that NO not
      only regulates glomerular capillary pressure but also decreases the sensitivity
      of the TGF mechanism.

PMID- 7524357
TI  - ATP and calcium modulation of nonselective cation channels in IMCD cells.
AB  - The mIMCD-3 cell line, developed from simian virus 40 transformed mice, was grown
      on coverslips for single-channel analysis of the apical membrane. An amiloride
      sensitive nonselective cation channel (NCATP) was demonstrated that occurred
      predominantly in excised patches. The selectivity sequence for NCATP was NH4+ =
      Na+ = K+ = Li+ = Rb+ > Cl-. The single-channel conductance was 24 pS and
      nonrectifying in 140 mM KCl or NaCl solutions. NCATP was not permeable to barium
      from the extracellular side. NCATP was not voltage gated but was activated
      spontaneously upon patch excision or after applying negative pressure (20-40
      mmHg) to an excised patch in bath solutions containing 1 microM Ca2+ [mean number
      of open channels (NPl) = 1.45]. NCATP was not activated when excised into a bath
      solution in which Ca2+ was reduced to 100 nM. The open probability of NCATP was
      reduced by 68% when 2 mM ATP was added to the intracellular side of an excised
      patch but was unaffected when 0.1 mM 8-bromoguanosine 3',5'-cyclic monophosphate
      was added to the intracellular side. In cell-attached patches, NCATP was
      activated upon response to a hyposmotic (210 mosmol/kgH2O) bathing solution
      containing 0.5 mM Ca2+ (NPo = 0.35). These results show that the mIMCD-3 cell
      line contains a volume-sensitive nonselective cation channel that is modulated by
      ATP and calcium but not guanosine 3',5'-cyclic monophosphate. It is postulated
      that NCATP may act to initiate the volume regulatory response in IMCD cells.

PMID- 7524358
TI  - Functional characterization and cell immunolocalization of AQP-CD water channel
      in kidney collecting duct.
AB  - Vasopressin-regulated water permeability of the kidney collecting duct is a key
      component of the urine concentration machinery. Recently, a cDNA for AQP-CD, the
      vasopressin-regulated water channel, initially reported as WCH-CD, has been
      isolated (K. Fushimi, S. Uchida, Y. Hara, Y. Hirata, F. Marumo, and S. Sasaki.
      Nature Lond. 361: 549-552, 1993). AQP-CD was expressed in oocyte membrane using a
      Xenopus expression vector, and functional characteristics of AQP-CD were
      examined. Osmotic water permeability (Pf) of oocytes expressing AQP-CD was 138 +/
      19 microns/s (mean +/- SE), 12 times greater than the control (11 +/- 3
      microns/s), 90% inhibited by 0.3 mM HgCl2, and weakly temperature dependent
      (energy of activation for Pf was 4.0 kcal/mol). Urea influx measured from 15-min
      [14C]urea uptake by oocytes injected with AQP-CD/expression vector 1 cRNA was 86
      +/- 17% of the control. Two-electrode voltage-clamp experiments revealed
      insignificant ion conductance of AQP-CD. Immunoblots of membranes from rat kidney
      medulla and oocytes expressing AQP-CD using anti-AQP-CD COOH-terminal antibody
      showed a 29-kDa protein and 35- to 50-kDa high-molecular-mass forms.
      Immunohistochemistry showed apical and subapical localization of AQP-CD in the
      collecting duct principal cells. Our results indicated that AQP-CD is a 29-kDa
      protein, a selective water channel, distinct from a urea channel, and localized
      to the membranes of vasopressin-sensitive components in kidney collecting duct
      principal cells.

PMID- 7524360
TI  - Renal transepithelial phosphate secretion: luminal membrane voltage and Ca2+
      dependence.
AB  - The role of apical membrane electrical potential, the possibility of K+ channel
      involvement, and the role of extracellular Ca2+ in transepithelial P(i) secretion
      were examined in primary monolayer cultures of flounder renal proximal tubule
      cells in Ussing chambers. Exposure to 200 nM thapsigargin (TG) significantly
      increased net P(i) secretion. In TG-stimulated tissues, substitution of 100 mM
      KCl for 100 mM NaCl in the luminal medium depolarized the apical membrane
      potential from -64 +/- 2.8 to -26 +/- 3.9 mV and strongly inhibited net P(i)
      secretion. In 32P(i)-preloaded tissues, cell-to-lumen exit of 32P(i) was
      significantly decreased to approximately 50% of control by high luminal K+ while
      cell-to-peritubular bath movement was unchanged. Addition of BaCl2 (2 mM) or
      charybdotoxin (20 nM) to the luminal surface significantly reduced TG-stimulated
      net P(i) secretion. The elevation of bath Ca2+ from 2 to 5 mM significantly
      increased secretory flux and decreased reabsorptive flux. The effect of TG on net
      P(i) secretion was reduced by the Ca2+ channel blocker verapamil (VE, 100 microM)
      to 65% of control and by calmodulin antagonist W-7 (20 microM) to 35% of control
      but it was not blocked by the protein kinase inhibitor H-7 (100 microM). VE also
      significantly inhibited the P(i) secretion induced by acidification of the
      peritubular bathing medium. The data indicate that transepithelial P(i) secretion
      induced by TG is significantly influenced by apical membrane electrical polarity,
      which may be regulated in part by Ca(2+)-activated K+ channels.

PMID- 7524362
TI  - Arginine metabolism in experimental glomerulonephritis: interaction between
      nitric oxide synthase and arginase.
AB  - L-Arginine is metabolized by two pathways: 1) by nitric oxide synthase (NOS) to
      nitric oxide (NO) and 2) by arginase forming urea and L-ornithine. Inflammatory
      responses may involve a balance between the pathways, as NO is cytotoxic and
      vasodilatory and L-ornithine is a promoter of cell proliferation and matrix
      synthesis. In experimental glomerulonephritis we have previously shown that NOS
      is activated in nephritic glomeruli. We have now examined both pathways of L
      arginine metabolism to study competition for L-arginine, temporal variation, and
      the sources of NOS and arginase. Acute in situ glomerulonephritis was induced in
      rats, and glomeruli were studied at 1, 4, and 7 days. Both NOS and arginase
      activities were present. There was temporal variation: NOS activity was highest
      on day 1 and arginase activity on day 4; both declined by day 7. Competition
      between the pathways was demonstrated by increased urea synthesis in the presence
      of NG-monomethyl-L-arginine, an inhibitor of NOS. Measurement of NOS and arginase
      activities in macrophages isolated from nephritic glomeruli showed that these
      cells were a major source of glomerular NOS but not arginase activity. In
      contrast, high arginase activity but low NO production was identified in cultured
      rat glomerular mesangial cells. These studies show differential temporal
      variation in expression of NOS and arginase pathways of arginine metabolism in
      experimental glomerulonephritis. We have found two factors that may contribute to
      this: 1) competition for substrate L-arginine between the two pathways and 2)
      different cellular sources. We hypothesize that the balance between these
      pathways is a mechanism regulating injury, hemodynamics, and mesangial cell
      proliferation.

PMID- 7524364
TI  - Interleukin-1 enhances beta-responsiveness of cardiac L-type calcium current
      suppressed by acidosis.
AB  - Modulation of the beta-adrenergic control of the cardiac L-type Ca2+ current
      (ICa) by human recombinant interleukin-1 beta (IL-1) was examined in guinea pig
      ventricular myocytes using the whole cell voltage-clamp technique. ICa was evoked
      in Cs(+)-loaded myocytes by depolarizing pulses from a holding potential of -40
      mV. In the presence of an acidic external solution (pH 5.8), the response of ICa
      to isoproterenol (Iso; 0.01 and 1 microM) was markedly decreased compared with
      control myocytes studied at pH 7.4. However, when cells were pretreated with 1
      ng/ml IL-1 and then exposed to acid media, beta-responsiveness was significantly
      increased compared with untreated cells. Despite this effect of IL-1, maximum ICa
      density with 0.01 and 1 microM Iso was still 51 and 58%, respectively, less than
      that measured at pH 7.4. The enhanced beta-responsiveness produced by IL-1 was
      eliminated by adding amiloride to block Na+/H+ exchange or protein kinase C
      inhibitors staurosporine (10 nM) and calphostin C (50 nM). However, a direct
      activator of protein kinase C, phorbol 12-myristate 13-acetate, did not mimic the
      effects of the cytokine. These data demonstrate that IL-1 partially restores the
      beta-adrenergic control of cardiac Ca2+ channels suppressed under acidic
      conditions. Moreover, they suggest that IL-1 acts by enhancing Na+/H+ exchange
      through a second messenger pathway that may involve protein kinase C. These
      cellular mechanisms may play a role in altering ventricular function during
      cytokine-mediated inflammatory processes that are initiated by myocardial
      ischemia.

PMID- 7524365
TI  - Effect of inhibition of NO synthase on vascular reactivity in a rat model of
      hyperdynamic sepsis.
AB  - To evaluate the role of nitric oxide (NO) in the attenuated vascular reactivity
      observed in sepsis, we utilized the specific NO synthase inhibitor N omega-nitro
      L-arginine methyl ester (L-NAME). Male Sprague-Dawley rats (n = 16) were
      randomized to either sepsis induced by cecal ligation and perforation (CLP; n =
      8) or sham procedure (Sham; n = 8). Vascular reactivity was assessed by measuring
      the pulmonary pressor response to hypoxia (HPV) (fractional inspired O2
      concentration = 0.08) and the pulmonary and systemic pressor response to an
      intravenous infusion of phenylephrine (1.5-6.0 micrograms.kg-1.min-1). Twenty
      four hours after surgery, CLP animals had significantly attenuated HPV compared
      with Sham animals. In response to hypoxia the change in total pulmonary vascular
      resistance during hypoxia was 0.008 +/- 0.004 and 0.021 +/- 0.006 mmHg.min-ml-1
      in CLP and Sham animals, respectively (P < 0.05). The pulmonary and systemic
      blood pressure response to phenylephrine was also attenuated in CLP compared with
      Sham animals. After L-NAME infusion (15 mg/kg), there was a significant
      augmentation of the HPV response in Sham animals. In contrast, the HPV response
      in CLP animals was unchanged after L-NAME. The attenuated pressor response to
      phenylephrine in neither the pulmonary nor the systemic circulation was changed
      after the administration of L-NAME. These data suggest that in rats, excess NO is
      not an important mediator of the attenuated vascular reactivity observed in
      sepsis.

PMID- 7524366
TI  - Angiotensin II maintains, but does not mediate, isoproterenol-induced cardiac
      hypertrophy in rats.
AB  - The role of angiotensin II (ANG II) in the development of isoproterenol (Iso)
      induced cardiac hypertrophy was examined in rats. Iso increased cardiac mass,
      left ventricular RNA-to-DNA ratio, and the cardiac content of both myosin heavy
      chain and hydroxyproline in a dose-dependent manner, indicating that Iso-induced
      cardiac hypertrophy involves growth of both muscle and connective tissue. Cardiac
      hypertrophy reverted within 11-14 days after cessation of Iso. Propranolol
      prevented development of Iso-induced cardiac hypertrophy but did not affect the
      rate of its reversal. The ANG II receptor blocker losartan (Los) did not
      significantly decrease the hypertrophic response to Iso. Los injected after
      cessation of Iso dramatically enhanced the reversal of cardiac hypertrophy, even
      in rats that received Los with Iso during the induction of Iso-induced cardiac
      hypertrophy. ANG II, injected continuously at a subpressor dose that did not
      affect heart weight when given alone, inhibited reversal of cardiac hypertrophy
      when given after cessation of Iso. Los did not significantly affect the induction
      of the protooncogene c-fos by Iso. We conclude that endogenous ANG II has a major
      function in maintaining Iso-induced cardiac hypertrophy but does not mediate its
      induction. This suggests that different interactive stimuli may be required for
      development of cardiac hypertrophy, i.e., for initiation and for maintenance.

PMID- 7524363
TI  - Functional and molecular evidence for Shaker-like K+ channels in rabbit renal
      papillary epithelial cell line.
AB  - The rabbit papillary epithelial cell line GRB-PAP1 was used to determine the ion
      transport characteristics of a model of the distal nephron and terminal
      collecting duct. When grown on permeable supports, monolayers developed a
      significant electrical resistance and a benzamil-sensitive short-circuit current,
      indicating that they had the property of electrogenic Na+ transport. Using the
      whole cell patch-clamp technique, we found that the dominant current in these
      cells was a slowly inactivating, time- and voltage-dependent K+ current. This
      current was activated by voltages more positive than -30 mV. At +30 mV, the peak
      outward currents were > 300 pA. The magnitude of the outward currents and their
      reversal potentials depended strongly on the extracellular concentration of K+
      and not on the extracellular concentration of Cl-. These currents were inhibited
      by either tetraethylammonium, 4-aminopyridine, charybdotoxin, or dendrotoxin.
      These characteristics, together with the kinetics of activation and inactivation,
      are the general characteristics of delayed rectifier channels seen in many muscle
      and neuronal cells. Because many of these types of channels share sequence
      homology with the Shaker family of channels cloned from Drosophila, we sought to
      identify a molecular correlate. Using reverse transcription followed by
      polymerase chain reaction to amplify Shaker-like sequences, we cloned and
      sequenced a single 881-bp fragment. The sequence shared identity with a recently
      reported rabbit Shaker channel that belongs to the subclass Kv 1.2. These data
      show that this renal papillary epithelial cell line, which has the capability of
      electrogenic Na+ transport, expresses functional delayed rectifier channels.

PMID- 7524361
TI  - PKC and high glucose stimulate collagen alpha 1 (IV) transcriptional activity in
      a reporter mesangial cell line.
AB  - Increased glomerular collagen IV mRNA in streptozotocin-diabetic rats and
      stimulation of matrix transcripts by high glucose levels in short-term mesangial
      cell culture provide evidence that stimulation of matrix synthesis is important
      in early diabetic glomerulopathy. To test whether transcriptional modulation of
      collagen IV genes is operative, we stably transfected a murine mesangial cell
      line with a "minigene" expressing luciferase driven by 5'-flanking and first
      intron regions of the murine COL4A1 gene to assess the response to high glucose
      and the associated signaling pathway. Luciferase activity was stimulated in a
      dose- and time-dependent manner [near-maximal stimulation in 450 mg/dl glucose
      (G450) was more than twofold the level in 100 mg/dl (G100) at 48 h]; high
      concentrations of D-mannitol were without effect. Neither low (2 ng/ml) nor high
      doses (2 micrograms/ml) of insulin modified luciferase activity in either G100 or
      G450. We next studied whether activation of protein kinase C (PKC) mediates the
      effect of high glucose. Treatment with the active phorbol ester phorbol 12
      myristate 13-acetate for 2-4 h or with a diacylglycerol analogue for 24 h
      significantly stimulated luciferase activity preferentially in G100; the PKC
      inhibitors staurosporine or calphostin C significantly reduced the activity
      preferentially in G450. Thus high glucose levels promote transcriptional activity
      of COL4A1 gene in this reporter mesangial cell line, perhaps through PKC
      activation.

PMID- 7524367
TI  - Rate-limiting steps in activation of cardiac Cl- current revealed by photolytic
      application of cAMP.
AB  - Single myocytes were obtained from guinea-pig ventricles, and the catecholamine
      induced Cl- current (ICl) was recorded by the patch-clamp method combined with
      the use of caged adenosine 3',5'-cyclic monophosphate (cAMP) and the
      concentration jump technique. The rapid bath application of isoprenaline was
      followed by a marked latency of approximately 1.7 s before a sigmoidal onset of
      the ICl activation, while the photolysis of caged cAMP was followed by no
      measurable latency. The ICl conductance was increased by increasing the
      concentration of caged cAMP with a threshold of approximately 5 microM and a one
      half effective concentration of 25 microM. On the other hand, the rate of the
      activation increased in proportion to the logarithm of the concentration of caged
      cAMP. When the ultraviolet flash was repeated or the myocytes were pretreated
      with either forskolin, 3-isobutyl-1-methylxanthine, or okadaic acid, the rate of
      the ICl activation accelerated, and the whole time course of the ICl activation
      became monoexponential. These findings suggest that both the production of cAMP
      and reactions on the multiple phosphorylation sites of the channel protein are
      major rate-limiting steps in the ICl activation.

PMID- 7524369
TI  - Cytokine-induced expression of nitric oxide synthase in C2C12 skeletal muscle
      myocytes.
AB  - Nitric oxide (NO) is an important mediator of diverse physiological and
      pathological responses. To determine whether NO production can be induced in
      skeletal muscle, we stimulated C2C12 mouse skeletal muscle myocytes with putative
      inducers of nitric oxide synthase (NOS). Neither lipopolysaccharide (LPS),
      interleukin-1 alpha (IL-1), tumor necrosis factor-alpha (TNF), nor interferon
      gamma (IFN) was able to stimulate nitrite production by C2C12 cells when
      administered alone. However, combinations of IFN with either TNF or IL-1 resulted
      in significant nitrite production; simultaneous stimulation of cells with all
      three cytokines resulted in significantly increased nitrite production compared
      with any combination of two cytokines. Northern analysis of RNA obtained from
      stimulated C2C12 cells revealed induction of a single mRNA band that precisely
      coincided with the mRNA band of mouse macrophage-inducible NOS (iNOS). Reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis followed by sequencing
      of the 5' 765 bases of the skeletal muscle iNOS cDNA demonstrated exact homology
      with mouse macrophage iNOS. These findings indicate that combinations of
      cytokines stimulate NO production in skeletal muscle cells via induction of the
      macrophage-type iNOS gene.

PMID- 7524368
TI  - Leukocyte rolling in venules of striated muscle and skin is mediated by P
      selectin, not by L-selectin.
AB  - Leukocyte rolling in post-capillary venules is mediated by adhesion molecules of
      the selectin family expressed on both leukocytes (L-selectin) and endothelial
      cells (E- and P-selectin). With the use of intravital fluorescence microscopy,
      the effects of antibodies against these selectins were analyzed in the skinfold
      chamber model of BALB/c mice and the ear model of homozygous hairless mice
      (hr/hr) that permit chronic observation of striated muscle and skin
      microcirculation in awake animals, respectively. Mice were injected intravenously
      with monoclonal antibodies (MAb) to murine L-selectin and E-selectin and affinity
      purified polyclonal antibodies to P-selectin. The antibodies, which are known to
      block cell adhesion, were tested by immunoprecipitation to selectively bind to L
      , E-, or P-selectin. Leukocyte rolling was a constant finding in both
      microcirculation models in the absence of inflammatory stimuli. In both models,
      injection of anti-P-selectin antibodies completely prevented baseline leukocyte
      rolling over an observation period of 2 h (P < 0.01 vs. baseline), while no
      effects were seen after administration of either anti-L-selectin or anti-E
      selectin MAb. Treatment with the isotype-matched control antibodies did not
      affect leukocyte rolling in either model. We conclude that leukocyte rolling in
      postcapillary venules of murine striated muscle and skin is a physiological
      process mediated via P-selectin, whereas L- and E-selectin appear not to play a
      significant role under these circumstances.

PMID- 7524370
TI  - A method for selective section of vagal afferent or efferent axons in the rat.
AB  - Although normally a mixed nerve, intracranially the vagus separates into dorsal
      rootlets that contain afferent axons and ventral rootlets that contain efferents.
      Surgical procedures are described for exposing the ventral surface of the
      occipital bone at the level where the vagus passes through the posterior
      lacerated foramen. When the foramen is expanded medially and the dura lanced, the
      intracranial course of the vagus can be observed by use of an operating
      microscope. Under these conditions, either the efferent or the afferent rootlets
      can be severed selectively. When the dorsal rootlets are divided and the
      contralateral trunk is cut below the diaphragm, a selective bilateral
      subdiaphragmatic afferent vagotomy is produced with unilateral sparing of the
      efferents. Cutting the efferents intracranially has the converse effect.

PMID- 7524371
TI  - Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats.
AB  - A cholecystokinin monoclonal antibody (CCK MAb) was used to immunoneutralize CCK
      to test the hypothesis that CCK produces satiety by an endocrine mechanism. We
      first characterized the effects of CCK MAb on pancreatic secretion. Conscious
      rats with jugular vein and bile-pancreatic duct cannulas received CCK MAb or
      control antibody intravenously 30 min before a 2-h maximal dose of CCK-8 (200
      pmol.kg-1.h-1 i.v.) or access to food. CCK MAb caused dose-related inhibition of
      amylase secretion. CCK MAb (2 mg/kg) completely blocked the response to CCK-8 and
      inhibited the response to food by 89%. In feeding experiments, rats with free
      access to food received CCK MAb or control antibodies (2 mg/kg iv) 2 h after
      lights off. CCK MAb had no effect on 1.5- or 3.5-h food intake. Another group of
      rats received CCK MAb (4 mg/kg i.v.) or a combined injection of type A and type B
      CCK receptor antagonists devazepide and L-365,260 (1 mg/kg each i.v.). CCK MAb
      had no effect on feeding, whereas the receptor antagonists stimulated 1-, 2-, 3-,
      and 4-h intake by 62, 45, 43, and 29%. These results suggest that endogenous CCK
      stimulates pancreatic enzyme secretion at least partially by an endocrine
      mechanism and produces satiety by a nonendocrine mechanism.

PMID- 7524372
TI  - Organization of vestibular inputs to nucleus tractus solitarius and adjacent
      structures in cat brain stem.
AB  - The vestibular system is involved in maintaining stable blood pressure and
      respiration during changes in posture and is essential for eliciting motion
      sickness-related vomiting. Because the nucleus tractus solitarius (NTS)
      participates in the regulation of sympathetic and inspiratory outflow and the
      triggering of emesis, we tested the hypothesis that this region receives
      vestibular inputs in cats. In one set of experiments, microinjections of the
      tracer Phaseolus vulgaris leucoagglutinin into the medial and inferior vestibular
      nuclei labeled projections to the middle and lateral regions of the NTS. In
      electrophysiological experiments, electrical stimulation of the vestibular nerve
      modified the firing rates of neurons located in the same regions. Some neurons
      with vestibular inputs received convergent signals from the abdominal vagus nerve
      and could potentially mediate motion sickness-related vomiting. Others received
      convergent baroreceptor inputs and could act as a substrate for some components
      of vestibulosympathetic reflexes. In contrast, inspiratory neurons in the dorsal
      respiratory group received little vestibular input, suggesting that
      vestibulorespiratory reflexes are mediated by cells located elsewhere.

PMID- 7524373
TI  - Risperidone, serotonergic mechanisms, and obsessive-compulsive symptoms in
      schizophrenia.

PMID- 7524376
TI  - Epithelial markers in malignant melanoma. A study of primary lesions and their
      metastases.
AB  - In order to determine epithelial markers in malignant melanoma in routinely
      processed paraffin sections and to compare the staining of primary (cutaneous)
      malignant melanomas and their metastases, we stained formalin-fixed paraffin
      sections of 13 primary and 18 metastatic malignant melanomas using the
      streptavidin-biotin peroxidase method by antibodies to S-100, vimentin, HMB-45,
      polyclonal carcinoembryonic antigen (CEA), monoclonal CEA, cytokeratins (CAM 5.2
      and broad-spectrum CKKES), and epithelial membrane antigen (EMA). All primary and
      most metastatic malignant melanomas showed positive staining with anti-S-100, HMB
      45, and anti-vimentin. Reactivity with polyclonal CEA was observed in 15 (48%) of
      the 31 lesions; 14 of them were metastatic. No lesion was reactive with
      monoclonal CEA. Significant cytokeratin (CK) staining was evident in only three
      (9.7%) lesions (all metastatic), which also stained specifically with anti-CK 18.
      EMA was observed only focally in two (6.5%) lesions. There was no correlation
      between epithelial markers staining of the primary tumours and their metastases.
      All lesions with CK or EMA staining showed concomitant extensive staining for S
      100, HMB-45, and vimentin. We conclude that (a) polyclonal CEA staining in
      malignant melanoma is not rare and is probably due to CEA-related molecules; (b)
      significant CK reactivity is rare and related to simple CK, such as CK 18; (c)
      epithelial marker reactivity is more common in metastases of malignant melanomas
      and is not correlated to the reactivity in their primary tumors. Considering our
      results and reports of positive S-100, vimentin, and HMB-45 in epithelial tumors,
      a wide panel of antibodies is recommended for the study of undifferentiated
      tumors.

PMID- 7524375
TI  - Pancreatic anastomotic leak after pancreaticoduodenectomy: incidence,
      significance, and management.
AB  - Anastomotic leak at the pancreaticojejunostomy remains a common and dreaded
      complication after pancreaticoduodenectomy. Our aim was to determine the
      incidence, presentation, methods of management, and preoperative and
      postoperative factors that influence the clinical outcome. We reviewed our
      collective experience with 375 consecutive patients undergoing
      pancreaticoduodenectomy from 1980 to 1992 for a variety of pathologic
      indications. Clinical, biochemical, intraoperative, and postoperative factors
      were reviewed in an attempt to determine prognostic factors. Sixty-six patients
      (18%) developed a pancreatic anastomotic leak as determined by increased amylase
      in drainage fluid (44%), radiographic documentation (41%), operative re
      exploration (9%), or percutaneous drainage of a peripancreatic, amylase
      containing fluid collection (6%). Most leaks (73%) were clinically insignificant
      and were managed by simple maintenance of intraoperatively placed drains. Active
      intervention was required in 18 patients (27%) and included percutaneous drainage
      in 8, completion pancreatectomy in 7, and reoperative drainage with or without
      anastomotic repair in 3. Although octreotide was used therapeutically in 13
      patients (20%), a significant, objective response was noted in only 1 patient.
      Five (8%) of the 66 patients died, all related directly to the pancreatic leak.
      The overall operative mortality was lower, 15 (4%) of 375 patients. Of the
      clinical, biochemical, intraoperative, and postoperative factors reviewed to
      determine prognostic factors, only postoperative intra-abdominal hemorrhage
      predisposed the patient to mortality as a result of the pancreatic anastomotic
      leak. We conclude that most anastomotic leaks at the pancreaticojejunostomy after
      pancreaticoduodenectomy can be managed conservatively. Use of octreotide to aid
      in closure of the pancreatic leak was disappointing, whereas patients with
      postoperative intra-abdominal hemorrhage or those requiring completion
      pancreatectomy to manage the anastomotic leak have increased mortality.

PMID- 7524377
TI  - Management of the thrombocytopenic cardiac surgical patient--a role for
      aprotinin?

PMID- 7524378
TI  - "The poem in the pain". The social significance of pain in Western civilization.

PMID- 7524374
TI  - Evidence of endothelial inflammation, T cell activation, and T cell reallocation
      in uncomplicated Plasmodium falciparum malaria.
AB  - To explain the observation that acute Plasmodium falciparum malaria is associated
      with a transient inability of peripheral blood cells to respond to antigenic
      stimulation in vitro, we have postulated the disease-induced reallocation of
      peripheral lymphocytes, possibly by adhesion to inflamed endothelium. We measured
      plasma levels of soluble markers of endothelial inflammation and T cell
      activation in 32 patients suffering from acute, uncomplication P. falciparum
      malaria, as well as in 10 healthy, aparasitemic control donors. All donors were
      residents of a malaria-endemic area of Eastern State Sudan. In addition, we
      measured the T cell surface expression of the interleukin-2 receptor (CD25) and
      the lymphocyte function-associated antigen (LFA-1; CD11a/CD18). We found that the
      plasma levels of all inflammation and activation markers were significantly
      increased in the malaria patients compared with the control donors. In addition,
      we found a disease-induced depletion of T cells with high expression of the LFA-1
      antigen, particularly in the CD4+ subset. The results obtained provide further
      support for the hypothesis of T cell reallocation to inflamed endothelium in
      acute P. falciparum malaria.

PMID- 7524379
TI  - [Stimulation of the lymphatic drainage in intensive care of acute myocardial
      infarct].
AB  - Under study was reogluman efficacy in the acute period of myocardial infarction.
      Timely administration of the drug to myocardial infarction patients was
      conductive to reduction of the duration and intensity of the painful syndrome,
      was associated with a reduction and even disappearance of congestion in the lungs
      within the first 2 days. These changes were paralleled by a more rapid
      normalization of the activities of all the blood serum lysosomal enzymes in the
      patients treated with reogluman as against the reference patients.

PMID- 7524380
TI  - [Use of high-dose aprotinin to stabilize hemostasis in artificial circulation].

PMID- 7524381
TI  - [Substantiation of the use of prostaglandin- and kininogenesis in general
      anesthesia and postoperative analgesia].
AB  - The expediency of introducing prostaglandin- and kininogenesis inhibitors
      (acelysin and kontrykal) into general anesthesia and postoperative analgesia has
      been substantiated and the advantages of the application of these specific
      nonopiate components of surgical analgesia have been shown. The above inhibitors
      alleviate local and general homeostasis disorders associated with excessive
      production of prostaglandins and kinins during surgical trauma and increase the
      efficacy of analgesia, reducing the need in narcotic analgesics.

PMID- 7524382
TI  - [Spinal anesthesia with lidocaine combined with moradol].
AB  - The efficacy of spinal anesthesia with lidocaine (1 mg/kg) combined with moradol
      (0.005 mg/kg) during urologic surgery has been compared with that of spinal
      anesthesia with lidocaine (1 mg/kg) combined with morphine (0.01 mg/kg). The
      adequacy of anesthesia was evaluated using common clinical and biological
      parameters. Analysis of the data obtained has shown that spinal anesthesia with
      lidocaine in combination with moradol is a simple and effective technique of
      regional anesthesia. A combination of local anesthetics with moradol ensures
      adequate anesthesia and pronounced prolonged postoperative analgesia and
      sedation. The absence of serious side effects makes it possible to substitute
      moradol for narcotic analgesics used in spinal anesthesia.

PMID- 7524383
TI  - Identification of new apolipoprotein B epitopes and haplotypes and their
      distribution in swine populations.
AB  - Results from comparative immunogenetic studies on inheritance and identification
      of four new apolipoprotein B (apoB) allotypes and three additional apoB
      haplotypes and their distribution in miniature and domestic swine are presented.
      Immunological surveys on the four new and 16 previously described Lpb allotypes
      and genetic analysis of their segregation in progenies, of miniature and domestic
      swine and their crosses, indicate that three new allotypes designated Lpb9, Lpb10
      and Lpb101 are individual (mutant) apoB epitopes, each representing a
      discriminating marker for one of the new apoB haplotypes specified by three new
      apoB alleles designated Lpb9, Lpb10 and Lpb101. The fourth allotype, Lpb20, is
      one of the common epitopes forming the alternative epitope pair with Lpb10, and
      is a constituent of each of the eight previously described and two new apoB
      haplotypes. The new apoB alleles have so far been found only in miniature swine,
      with Lpb10 being the most frequent in the Gottingen, Vietnamese Pot-belly and
      Japanese Miniature, Lpb9 was detected only in Minnesota Miniature and Lpb101 only
      in Vietnamese Potbelly. The common allotype, Lpb20, shares immunological
      similarities with human apoB indicating its ancestral origin, whereas none of the
      alloreagents detecting the three individual apoB variants, Lpb9, Lpb10 or Lpb101,
      showed cross-reactivity with human apoB, suggesting their exclusive swine origin
      and evolvement during speciation through mutations.

PMID- 7524385
TI  - The role of endoscopic retrograde cholangiopancreatography with laparoscopic
      cholecystectomy in the management of choledocholithiasis.
AB  - Perioperative endoscopic retrograde cholangiopancreatography (ERCP) and
      sphincterotomy (ES) offer the ability to remove common bile duct stones (CBDS)
      and still use the laparoscopic technique for cholecystectomy. The accuracy of
      predicting choledocholithiasis has been variable in several studies. The
      indications and complications of perioperative ERCP and ES with laparoscopic
      cholecystectomy (LC) are presented here. Between 6/1/90 and 11/11/93, 484 LC were
      performed at Santa Barbara Cottage Hospital. A total of 38 patients underwent
      perioperative ERCP; 33 patients underwent preoperative ERCP with 3/33 (9%)
      failing to cannulate the ampulla; 15 patients had choledocholithiasis; and 14/15
      (93%) were cleared by ES. Fifteen patients had a normal CBD on ERCP. There were
      no deaths in this group of patients, seven of 38 (18%) had complications,
      including bleeding and post ERCP hyperamylasemia. Patients who had a normal CBD
      and underwent preoperative ERCP (9/15, 60%) had a history of gallstone
      pancreatitis or hyperamylasemia that was resolved or resolving before ERCP.
      Patients without stones on ERCP or cholangiogram (11/15, 73%) had a normal
      bilirubin (avg. 1.0 mg/dL; Range 0.4-2.3). Patients with choledocholithiasis
      (8/15, 53%) had a history of jaundice or elevated bilirubin before ERCP (avg.
      2.59 mg/dL; range 0.2-9.3). ERCP with ES and laparoscopic cholecystectomy is a
      safe and effective method for the management of symptomatic cholelithiasis with
      choledocholithiasis. A history of gallstone pancreatitis or hyperamylasemia that
      is resolving or resolved in the absence of an elevated bilirubin does not require
      preoperative ERCP before LC with cholangiogram.

PMID- 7524384
TI  - Hypersensitivity to ketoconazole.
AB  - We report a patient who experienced generalized urticaria and facial angioedema
      following oral administration of ketoconazole. Skin prick tests with ketoconazole
      and oral challenge were positive. Conjugates of ketoconazole with human serum
      albumin were used for the in vitro study, obtaining a positive result in the
      histamine release test. No significant levels of IgE antibodies to ketoconazole
      were found by RAST. Controls did not react to any of these tests. These results
      suggest that the patient developed a type I hypersensitivity reaction to
      ketoconazole. In this case, skin prick tests with ketoconazole and histamine
      release test with a conjugate of ketoconazole with human serum albumin were
      useful in ketoconazole hypersensitivity diagnosis. Finally, skin tests with other
      imidazole agents were carried out, including metronidazole, ornidazole, and
      fluconazole that were negative.

PMID- 7524386
TI  - [WHO laboratory manual for the examination of human seminal fluid and the
      interaction of sperm with cervical mucus].

PMID- 7524387
TI  - A model system using fetal hemoglobin to distinguish fetal cells enriched from
      maternal blood.

PMID- 7524388
TI  - High-speed flow cytometric analysis and sorting of human fetal cells from
      maternal blood for molecular characterization.

PMID- 7524389
TI  - Strategies for the detection of autosomal fetal DNA sequence from maternal
      peripheral blood.

PMID- 7524390
TI  - Clinical trials and experience: Boston.
AB  - Our cumulative experience continues to validate the fetal nucleated erythrocyte
      as the target fetal cell type of choice, primarily because it reflects the
      cytogenetic status of the current pregnancy. Additional cell types, such as the
      granulocyte, await further study. Quantitative PCR is a sensitive and useful new
      method that can facilitate rapid comparisons between cell separation methods or
      different monoclonal antibodies. It can also be used on patient material to
      determine final purity of the enriched maternal samples. If the purity is too
      low, FISH studies will be complicated by the presence of thousands of maternal
      cells. Our planned studies include an analysis of why aneuploid pregnancies
      appear to have a higher number of fetal cells in the maternal circulation. We are
      also studying the timing of the fetomaternal transfer of cells with qPCR analysis
      of sorted maternal samples drawn weekly from well-dated women. We are
      continuously improving our methods (both in separations and antibodies) to reach
      a fetal cell purity of at least 20% for cytogenetic diagnosis by FISH studies.
      With the knowledge obtained thus far by us and by others, such a goal appears to
      be achievable within the near future.

PMID- 7524392
TI  - Biology of alpha2-Macroglobulin, its Receptor, and Related Proteins. Proceedings
      of a conference. Woods Hole, Massachusetts, October 11-14, 1993.

PMID- 7524391
TI  - The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related
      protein and the receptor-associated protein. An overview.

PMID- 7524393
TI  - Binding and endocytosis of proteins mediated by epithelial gp330.

PMID- 7524394
TI  - Molecular analysis of the human and mouse alpha 2M family.

PMID- 7524395
TI  - Role of internal thiol esters in the alpha-macroglobulin-proteinase binding
      mechanism.

PMID- 7524396
TI  - Alpha 2M in the horseshoe crab. A structural and functional invertebrate
      homologue.

PMID- 7524397
TI  - Electron microscopic visualization of the human alpha 2-macroglobulin receptor
      and its interaction with alpha 2-macroglobulin/chymotrypsin complex.

PMID- 7524398
TI  - Structure-function relationships of human alpha 2-macroglobulin. Three
      dimensional structures of native alpha 2-macroglobulin and its methylamine and
      chymotrypsin derivatives.

PMID- 7524400
TI  - The proteinase-binding reaction of alpha 2M.

PMID- 7524399
TI  - Three-dimensional reconstruction of human alpha 2-macroglobulin and refinement of
      the localization of thiol ester bonds with monomaleimido nanogold.

PMID- 7524401
TI  - Alpha 2-macroglobulin. A multifunctional binding and targeting protein with
      possible roles in immunity and autoimmunity.

PMID- 7524403
TI  - Alpha 2-macroglobulin: a sensor for proteolysis.

PMID- 7524402
TI  - Alpha 2-macroglobulin and the alpha 2-macroglobulin receptor/LRP. A growth
      regulatory axis.

PMID- 7524405
TI  - Regulation of platelet-derived growth factor (PDGF) and alveolar macrophage
      derived PDGF by alpha 2-macroglobulin.
AB  - In vitro findings suggest that alpha 2M is an important regulator of PDGF
      stimulated fibroblast proliferation and chemotaxis. Native alpha 2M binds to PDGF
      and prevents PDGF from interacting with its receptor, but serves as an
      extracellular reservoir for the growth factor, which can be released over time in
      a controlled fashion to interact with the PDGF-alpha or -beta receptor.
      Methylamine-activated alpha 2M synergistically enhances PDGF-induced cell growth,
      whereas plasmin-activated alpha 2M inhibits PDGF-stimulated fibroblast
      proliferation. The reason for the difference in the effect of these two receptor
      recognized alpha 2Ms is unknown. PDGF secreted by rat alveolar macrophages is
      bound to homologues of human alpha 2M and it has been suggested that PDGF action
      in the lung is tightly controlled during normal tissue remodeling. It is
      important to consider another regulator of PDGF termed SPARC (secreted protein,
      acidic and rich in cysteine), which inhibits the binding of PDGF-BB and -AB to
      cell-surface PDGF-beta receptors. SPARC could modulate PDGF activity during
      inflammation and tissue repair by limiting the availability of dimers containing
      the PDGF B chain. Future studies should address the relative importance of SPARC
      and alpha 2M in regulating PDGF-induced chemotaxis and proliferation. During
      inflammation or during the progression of fibroproliferative lung disease, the
      regulation of PDGF might be lost. For example, oxidative bursts from inflammatory
      cells (neutrophils and eosinophils) functionally inactivate alpha 2M. Thus,
      inhaled environmental insults (particles and oxidants) could perturb the normal
      growth regulatory signaling system between cells via the network that includes
      cytokines, alpha 2M, and proteinases.

PMID- 7524406
TI  - Modulation of immune cell activities by alpha 2-macroglobulin. A proposed
      physiological role based on activation kinetics and model vaccine studies.

PMID- 7524404
TI  - Regulation of alpha 2-macroglobulin gene expression by interleukin-6.

PMID- 7524407
TI  - Significance of the regulation of plasma kallikrein by alpha 2M.

PMID- 7524409
TI  - Binding of epidermal growth factor to human alpha 2-macroglobulin. Significance
      for cytokine alpha 2-macroglobulin interactions.

PMID- 7524411
TI  - Alpha 2-macroglobulin in the regulation of pericellular plasminogen activation of
      human tumor cells.

PMID- 7524410
TI  - Alpha 2-macroglobulin and the control of adrenocortical steroidogenic function.

PMID- 7524414
TI  - Determination of total and transformed alpha 2-macroglobulin by a monoclonal
      antibody immunosorption assay in patients with different diseases.

PMID- 7524413
TI  - Feedback mechanisms between alpha 2M and TGF beta 1 reduce extracellular matrix
      synthesis of liver fat-storing cells.

PMID- 7524412
TI  - Kinetics of proteinase trapping by alpha 2M.

PMID- 7524408
TI  - Alpha 2-macroglobulin/transforming growth factor-beta 1 interactions. Modulation
      by heparin-like molecules and effects on vascular smooth muscle cells.

PMID- 7524416
TI  - The cleavage of the bait region of alpha 2-macroglobulin by human
      immunodeficiency virus proteinases and by astacin.

PMID- 7524415
TI  - Uptake of methylamine-activated alpha 2-macroglobulin by rat liver.
AB  - Serum clearance of alpha 2M-Me or alpha 2M-Tr is rapid and identical. Alpha 2M-Tr
      is almost exclusively taken up in the liver by the parenchymal cells; the uptake
      of alpha 2M-Me is equally shared between endothelial and parenchymal cells.
      Blocking the scavenger receptor on endothelial cells by polyinosinic acid reduces
      the uptake of alpha 2M-Me to 40% of the control value; under these conditions,
      alpha 2M-Me is only associated with the parenchymal cells. These results show the
      following: (1) activation of alpha 2M by methylamine or trypsin is different; (2)
      the scavenger receptor on endothelial cells functions as a system for the uptake
      of alpha 2M-Me in addition to the specific alpha 2M receptor on parenchymal
      cells.

PMID- 7524418
TI  - Crystallization of proteins of the alpha 2-macroglobulin superfamily.

PMID- 7524417
TI  - Human alpha 2-macroglobulin as a cytokine-binding plasma protein. A study with rh
      interleukin-1 beta and rh-interleukin-6.

PMID- 7524420
TI  - Alpha 2-macroglobulin in experimental and human Chagas' disease.

PMID- 7524419
TI  - Disulfide bond formation by methanethiolation of the thiol ester sulfhydryl group
      of alpha 2M.

PMID- 7524421
TI  - Binding of nerve growth factor to different forms of alpha 2-macroglobulin.

PMID- 7524423
TI  - Alpha 2-macroglobulin: a ferritin-binding protein.

PMID- 7524424
TI  - The promoter of the human alpha 2-macroglobulin gene binds HNF-4 or a related
      nuclear factor for its expression in hepatocytes and lung fibroblasts.

PMID- 7524422
TI  - Monoamine-activated alpha 2-macroglobulin inhibits neurite outgrowth, survival,
      choline acetyltransferase, and dopamine concentration of neurons by blocking
      neurotrophin-receptor (trk) phosphorylation and signal transduction.

PMID- 7524426
TI  - Ligation of alpha 2M receptors with alpha 2M-methylamine stimulates the
      activities of phospholipase C, phospholipase A2, and protein kinase C in murine
      peritoneal macrophages.

PMID- 7524425
TI  - Recombinant alpha 2M receptor binding domain binds to the alpha 2M receptor with
      high affinity.

PMID- 7524427
TI  - Receptors for alpha 2-macroglobulin are present on human dermal fibroblasts, but
      not on human keratinocytes.

PMID- 7524428
TI  - Cloning and expression of the 15-kDa C-terminal peptide from the human alpha 2
      macroglobulin as a fusion-protein product in a prokaryotic cell line.

PMID- 7524429
TI  - Characterization of the genes coding for the murinoglobulins and expression in
      vivo.

PMID- 7524431
TI  - Structure and targeting in ES cells of the gene coding for mouse alpha 2
      macroglobulin.

PMID- 7524434
TI  - Identification of domains on the 39-kDa protein that inhibit the binding of
      ligands to the low density lipoprotein receptor--related protein.

PMID- 7524433
TI  - Binding of lipoprotein lipase to alpha 2-macroglobulin.

PMID- 7524432
TI  - Temperature-dependent biosynthesis of thiol esters in baculovirus recombinant
      alpha 2M and PZP.

PMID- 7524430
TI  - Expression of mouse alpha 2M and its receptor in vivo.

PMID- 7524436
TI  - Neuropeptide participation in canine laryngeal sensory innervation.
      Immunohistochemistry and retrograde labeling.
AB  - We investigated the quantitative participation of calcitonin gene-related peptide
      (CGRP), substance P (SP), and leu-enkephalin (ENK) in canine laryngeal sensory
      innervation by immunohistochemistry in combination with retrograde labeling using
      the recently introduced retrograde tracer cholera toxin subunit B-conjugated gold
      (CTBG). In the nodose ganglion, neurons labeled from the internal branch of the
      superior laryngeal nerve with CTBG were investigated immunohistochemically by
      means of antisera against CGRP, SP, and ENK. The percentages of neurons
      immunoreactive to each neuropeptide were as follows: CGRP 81.5%, SP 24.5%, and
      ENK 7.0%. These results suggest that CGRP is the main sensory neurotransmitter in
      canine laryngeal sensory innervation.

PMID- 7524435
TI  - The role of alpha 2M receptor/LRP in chylomicron remnant metabolism.
AB  - A strong candidate for the long-searched CR receptor might be the alpha 2MR/LRP.
      Presently, we are overseeing a whole series of in vitro experiments from
      different laboratories that show that LRP expresses all the features for being
      such a receptor protein. LRP is localized on the liver cell surface, as well as
      on most other animal cells. It recognizes apo E-enriched lipoproteins as beta
      VLDL and CR. There is evidence that CR contain LPL and it has been demonstrated
      that LPL binds with high affinity to LRP. This has been shown in cell binding
      experiments with subsequent cross-linking and in direct assays on purified
      receptor protein. HL, which is expressed in liver cells and localized at the
      liver cell surface, is also able to bind to LRP. Moreover, LRP is found in
      endosomes and can mediate the uptake of beta-VLDL and CR. Further studies are
      necessary to evaluate its role in vivo as well as its regulation. The interplay
      between the different ligands of this large multifunctional receptor protein
      needs to be clarified. It should be emphasized here that, by describing LPL as a
      new mediator of CR uptake in the liver and by providing evidence for a direct
      interaction between LPL and LRP, the role of LRP in the remnant catabolism has
      become even more likely.

PMID- 7524438
TI  - Band heterotopia: correlation of outcome with magnetic resonance imaging
      parameters.
AB  - The "band heterotopia" or "double cortex" is a brain anomaly that is presumed to
      result from a premature arrest of neuronal migration. Patients with this anomaly
      are reported to have a variable clinical course that has been, heretofore,
      unpredictable. The clinical records and magnetic resonance (MR) imaging studies
      of 27 patients with band heterotopia were retrospectively reviewed in an attempt
      to determine whether imaging findings are useful in predicting clinical outcome
      of affected patients. Statistical analyses revealed the following correlations:
      (1) severity of T2 prolongation in the brain with motor delay (p = 0.03); (2)
      degree of ventricular enlargement with the age of seizure onset (p = 0.04), and
      with development and intelligence (p = 0.04); (3) severity of pachygyria with the
      age of seizure onset (p = 0.01), seizure type (p = 0.03), and an abnormal
      neurologic examination (p = 0.002); (4) parietal involvement with delayed speech
      development (p = 0.05); (5) occipital involvement with age of seizure onset (p =
      0.006); (6) age of seizure onset with development and intelligence (p = 0.03) and
      with an abnormal neurologic examination (p = 0.04); and (7) severity of the
      pachygyria and thickness of band with development of symptomatic generalized
      epilepsy (p = 0.002 and p = 0.02, respectively) and Lennox-Gastaut syndrome (p =
      0.002 and p = 0.01, respectively).

PMID- 7524437
TI  - mRNA in-situ hybridization using biotinylated oligonucleotide probes:
      implications for the diagnostic laboratory.
AB  - It is now possible to detect low copy numbers of messenger ribonucleic acid
      (mRNA) while retaining good histologic morphology for the determination of
      specific gene expression in diseased tissues. This technology will allow the
      pathologist to provide important prognostic information about tumors (expression
      of oncogenes and growth factors), to identify the subclones within the tumor
      which may be most likely to metastasize (expression of adhesion molecules and
      proteases) and to identify etiologic genetic aberrations (viral insertions). A
      technique for in-situ hybridization to mRNA has been developed for use in
      formalin fixed paraffin embedded tissues which is suitable for a hospital
      histology laboratory. Optimal conditions for the procedure were determined by
      using a biotinylated poly (d)T oligonucleotide probe. Results were dependent on
      the tissue type, fixation time, condition of the tissue prior to fixation, and
      degree of digestion before hybridization. The temperature and conditions of
      hybridization were optimized so that the poly d(T) control probe and the longer
      test probe could be run simultaneously. Streptavidin and avidin alkaline
      phosphatase detection systems were tested using levamisole to minimize background
      staining, and a biotin blocking agent to reduce reaction to renal tubular biotin.
      Increasing the temperature of stringency washes did not significantly improve the
      specificity but had a markedly detrimental effect on tissue morphology. The mRNA
      appears to remain stable within routinely fixed surgical material over long
      periods of time allowing for large retrospective studies. A review of c-erbB-2
      expression in 16 human breast lesions was carried out comparing mRNA in-situ
      hybridization to immunoperoxidase and cytosolic methods. By direct localization
      of both message and antigen, it was possible to demonstrate focal positivity that
      cytosolic methods did not detect. Aberrant translation was noted in one case, and
      c-erbB-2 expression in non-malignant breast was detected in two cases.

PMID- 7524439
TI  - Enzymatic properties and sensitivity to inhibitors of human immunodeficiency
      virus type 1 (HIV-1) reverse transcriptase with Glu-138-->Arg and Tyr-188-->His
      mutations.
AB  - Two mutants of HIV-1 reverse transcriptase (RT), Tyr-188-->His and Glu-138-->Arg
      have been prepared and their catalytic properties and sensitivities to inhibitors
      studied. As compared to wild type RT, a reduction in catalytic efficiency and
      turn over number was observed, especially for the Tyr-188-->His mutant. The non
      nucleoside inhibitors nevirapine, L-697,661 and 9-Cl-TIBO caused a mixed type of
      inhibition of RT (Arg-138) with respect to substrate, and with the exception of a
      non-competitive inhibition by nevirapine, also a mixed type of inhibition of RT
      (His-188). Foscarnet (PFA) caused a non-competitive type of inhibition of RT (Arg
      138) and a mixed inhibition of RT (His-188). The inhibition by ddG-TP was
      competitive with both mutant RTs. Inhibition by nevirapine gave IC50 values of
      0.15, 0.23 and 0.72 microM; by 9-Cl-TIBO of 0.20, 2.50 and 10.3 microM; by L
      697,661 of 0.064, 0.28 and 0.60 microM; by ddGTP of 0.13, 0.14 and 0.02 microM;
      by PFA of 17.0, 48.0 and 15.0 microM for RT wt, RT (Arg-138) and RT (His-188),
      respectively.

PMID- 7524441
TI  - Associations of methanotrophs with the roots and rhizomes of aquatic vegetation.
AB  - Results of an in vitro assay revealed that root-associated methane consumption
      was a common attribute of diverse emergent wetland macrophytes from a variety of
      habitats. Maximum potential uptake rates (Vmaxp) varied between about 1 and 10
      micromol g (dry weight)-1 h-1, with no obvious correlation between rate and gross
      morphological characteristics of the plants. The Vmaxp corresponded to about 2 x
      10(8) to 2 x 10(9) methanotrophs g (dry weight)-1, assuming that the root
      associated methanotrophs have cell-specific activities comparable to those of
      known isolates. Vmaxp varied seasonally for an aquatic grass, Calamogrostis
      canadensis, and for the cattail, Typha latifolia, with highest rates in the late
      summer. Vmaxp was well correlated with ambient temperature for C. canadensis but
      weakly correlated for T. latifolia. The seasonal changes in Vmaxp, as well as
      inferences from apparent half-saturation constants for methane uptake (Kapp;
      generally 3 to 6 microM), indicated that oxygen availability might be more
      important than methane as a rate determinant. In addition, roots incubated under
      anoxic conditions showed little or no postanoxia aerobic methane consumption,
      indicating that root-associated methanotrophic populations might not tolerate
      variable oxygen availability. Hybridization of oligodeoxynucleotide probes
      specific for group I or group II methylotrophs also varied seasonally. The group
      II-specific probe consistently hybridized to a greater extent than the group I
      probe, and the relative amount of group II probe hybridization to C. canadensis
      root extracts was positively correlated with Vmaxp.

PMID- 7524440
TI  - Identifying members of the domain Archaea with rRNA-targeted oligonucleotide
      probes.
AB  - Two 16S rRNA-targeted oligonucleotide probes were designed for the archaeal
      kingdoms Euryachaeota and Crenarchaeota. Probe specificities were evaluated by
      nonradioactive dot blot hybridization against selected reference organisms. The
      successful application of fluorescent-probe derivatives for whole-cell
      hybridization required organism-specific optimizations of fixation and
      hybridization conditions to assure probe penetration and morphological integrity
      of the cells. The probes allowed preliminary grouping of three new
      hyperthermophilic isolates. Together with other group-specific rRNA-targeted
      oligonucleotide probes, these probes will facilitate rapid in situ monitoring of
      the populations present in hydrothermal systems and support cultivation attempts.

PMID- 7524444
TI  - Cometabolic degradation of trichloroethylene by Pseudomonas cepacia G4 in a
      chemostat with toluene as the primary substrate.
AB  - Pseudomonas cepacia G4 is capable of cometabolic degradation of trichloroethylene
      (TCE) if the organism is grown on certain aromatic compounds. To obtain more
      insight into the kinetics of TCE degradation and the effect of TCE transformation
      products, we have investigated the simultaneous conversion of toluene and TCE in
      steady-state continuous culture. The organism was grown in a chemostat with
      toluene as the carbon and energy source at a range of volumetric TCE loading
      rates, up to 330 mumol/liter/h. The specific TCE degradation activity of the
      cells and the volumetric activity increased, but the efficiency of TCE conversion
      dropped when the TCE loading was elevated from 7 to 330 mumol/liter/h. At TCE
      loading rates of up to 145 mumol/liter/h, the specific toluene conversion rate
      and the molar growth yield of the cells were not affected by the presence of TCE.
      The response of the system to varying TCE loading rates was accurately described
      by a mathematical model based on Michaelis-Menten kinetics and competitive
      inhibition. A high load of 3,400 mumol of TCE per liter per h for 12 h caused
      inhibition of toluene and TCE conversion, but reduction of the TCE load to the
      original nontoxic level resulted in complete recovery of the system within 2
      days. These results show that P. cepacia can stably and continuously degrade
      toluene and TCE simultaneously in a single-reactor system without biomass
      retention and that the organism is more resistant to high concentrations and
      shock loadings of TCE than Methylosinus trichosporium OB3b.

PMID- 7524443
TI  - Degradation of 2,4-dichlorophenoxyacetic acid by Pseudomonas cepacia DBO1(pRO101)
      in a dual-substrate chemostat.
AB  - To determine the effect of a secondary carbon source on biodegradation of a
      chloroaromatic compound, Pseudomonas cepacia DBO1(pRO101) was grown in continuous
      cultures on basal salts media containing various mixtures of 2,4
      dichlorophenoxyacetic acid (2,4-D) and succinate. Both succinate and 2,4-D were
      metabolized over the entire range of dilution rates and compositions analyzed
      (0.05 to 0.6 h-1). 2,4-Dichlorophenol (DCP), the only intermediate detected,
      accumulated to significant amounts (10 to 21 mg/liter) in the chemostat only when
      the dilution rate was 0.4 h-1 or greater. At these concentrations, DCP reduced
      the apparent growth rate of P. cepacia DBO1(pRO101) in batch cultures by 15 to
      35% over the apparent growth rate on succinate alone. Succinate fed to the
      chemostat increased the cell density as well as the percentage of 2,4-D that was
      consumed at each dilution rate. When the amount of succinate in the feed exceeded
      the amount of 2,4-D, the specific rates of 2,4-D degradation in the chemostat or
      by washed cells were significantly lower than the specific rates for cells grown
      on 2,4-D alone, suggesting repression by succinate. However, when the amount of
      2,4-D in the feed exceeded the amount of succinate, the specific rates of 2,4-D
      degradation remained at values equivalent to or higher than the specific rate for
      cells grown on 2,4-D alone. DCP accumulated significantly in the washed-cell
      assay, suggesting that the level of DCP hydroxylase is rate limiting.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7524442
TI  - PCR-based preparation of 23S rRNA-targeted group-specific polynucleotide probes.
AB  - DNA coding for a variable region within domain III of bacterial 23S rRNA was used
      as the target for group-specific polynucleotide hybridization probes. The
      corresponding rDNA was amplified in vitro by the PCR technique in combination
      with a pair of primers specific for flanking conserved target sites. The
      amplified fragments were cloned or used directly as probes. RNA probes were
      generated by in vitro transcription of cloned or amplified rDNA. The probes were
      labeled by incorporating modified nucleotides during in vitro DNA amplification
      or in vitro transcription or by random priming. The use of in vitro transcribed
      single-stranded RNA probes instead of double-stranded DNA probes provided
      stronger hybridization signals. Group-specific probes were prepared from genomic
      DNAs or directly from cells of Acinetobacter calcoaceticus, Alcaligenes faecalis,
      Aeromonas hydrophila, Nannocystis exedens, Pseudomonas aeruginosa, Pseudomonas
      fluorescens, and Pseudomonas stutzeri.

PMID- 7524445
TI  - Enhanced sensitivity in PCR detection of Listeria monocytogenes in soft cheese
      through use of an aqueous two-phase system as a sample preparation method.
AB  - A sample treatment method based on an aqueous two-phase system containing
      polyethylene glycol and dextran was developed for enhancing sensitivity in the
      detection of Listeria monocytogenes in soft cheese with PCR. The results suggest
      that the improved detection sensitivity following partitioning of the cheese
      homogenate in an aqueous two-phase system may be due to partitioning of the PCR
      inhibitors to the polyethylene glycol phase.

PMID- 7524448
TI  - Arterial infusion chemotherapy in far advanced cancer.
AB  - From 1978 to 1994, more than 2000 advanced cancers were treated by arterial
      infusion chemotherapy in the Department of Surgery, Kaohsiung Medical College
      Hospital. During these 16 years there are a lot of improvements in arterial
      therapy. The catheter changed from external catheter to implantable port catheter
      system. The infusion pump changed from spring driven pump to more accurate
      battery operated electric pump. But the principle of the higher the regional
      tumor drug exposure, the better the treatment result is the same. There are 3
      main factors affecting the successful treatment, proper placement of the
      catheter, suitable selection of the drugs and adequate regional tumor blood
      supply. The first two factors can be improved by learning and experience.
      However, we can do little about the third one. The blood supply of the tumor had
      decided most of the outcome of the treatment. Those tumors over locations with
      very rich blood supply such as cancers of head, breast, external genitals and
      hands, always respond better to chemotherapy no matter the drugs were given
      regionally or systemically. Of course if the anticancer drug was administered by
      arterial route, very high concentration of anticancer drug can be delivered to
      the tumor region to induced rapid shrinkage of the tumor within a relative short
      time.

PMID- 7524446
TI  - A phylogenetic tree of 16S rRNA sequences from sulfate-reducing bacteria in a
      sandy marine sediment.
AB  - The divergence of 16S rDNA sequences in marine sediment was investigated. Twenty
      unique partial sequences were found among 33 cloned following PCR. Thirteen
      shared 82 to 91% similarity with sequences of delta subclass sulfate-reducing
      bacteria. Three contained the target sequence for a sulfate-reducing bacterium
      specific oligonucleotide probe designed from pure-culture studies.

PMID- 7524449
TI  - [Drug distribution and antitumor effect of bleomycin incorporated in poly DL
      lactic acid in rats].
AB  - Two bleomycin (BLM)-containing agents (BLM-PLA, BLM-SOL) were prepared, and the
      drug distribution and antitumor effect were studied. BLM-PLA is an agent in which
      BLM is incorporated into biodegradable low-molecular-weight polylactic acid, and
      BLM-SOL is an aqueous solution of BLM. BLM-PLA or BLM-SOL was subcutaneously
      administered in the back of rats. When BLM-PLA was implanted, high BLM activity
      of the connective tissues near the implants was maintained for 2 weeks. On the
      other hand, BLM activity was very low when BLM-SOL was administered. The effects
      of BLM-PLA, BLM-SOL and nontreatment on tumor growth and survival time were
      compared using subcutaneous tumor of Yoshida sarcoma in 21 rats each. The
      survivors and mean survival time in BLM-PLA group, BLM-SOL group and nontreatment
      group was 14 and 44.6 days, 5 and 23.7 days, and 0 and 11.3 days, respectively.
      BLM-PLA was superior to BLM-SOL in both drug distribution and antitumor effect,
      and consequently BLM-PLA could be a useful tool in loco-regional chemotherapy.

PMID- 7524450
TI  - [The duty of hospice for holistic medicine].
AB  - The hospice program has a sense of absolute in the context of the provision of
      treatment by the medical establishment. The aim of the medical establishment is
      humanistic treatment. The aim of the hospice program is to allow doctors in
      charge, thru their medical skills, to make the most effort for the life of the
      patient. As such, the goal of the hospice program is not just to ease the
      physical pain of terminal patients, but rather to help the patient live the
      remainder of his or her life in a meaningful way, offering intensive support and
      energy to help the patient challenge and even defy his or her life. Today in
      Japan, the hospice care program has established a system of renumeration for use
      of special cancer wards and pain-easing treatments. Because of this, hospice care
      is becoming wide-spread among medical care organizations. Such wide-spread care
      is a very desirable thing. But if the economic value of hospice care is only to
      ease physical pain, then hospice care is essentially a formless act. If we do not
      effect the appropriate value both socially and economically, one wonders if the
      hospice care in Japan will be able to develop the correct approach.

PMID- 7524453
TI  - [Transurethral prostatic thermotherapy with microwaves (prostatron system) in
      bladder obstruction secondary to benign prostatic hypertrophy].
AB  - Since April, 1992, 178 patients with symptomatic benign prostatic hyperplasia
      were treated by TUMT (363 treatments). Before entering the study, all patients
      had a Madsen symptom score of > 8, peak flow rate of < 15 ml/s, or average flow
      rate of < 10 ml/s, and post voiding residual urine of < 300 ml/s. The prostatic
      length was classified into group I < 50 mm (101 patients) and group II < 50 mm
      (77 patients). TUMT with the Prostatron device (Technomed) was performed in one,
      two or three session(s) of one or two hour(s) with analgosedation and on an
      outpatient basis. After treatment all patients were catheterized for 1-3 weeks;
      the morbidity rate was very low. Three and six months after treatment, the Madsen
      symptom score, peak flow rate, average flow rate and postvoiding residual urine
      improved to a high statistical significance in both groups. TUMT for benign
      prostatic outflow obstruction proved to be an effective treatment throughout the
      study period, with minimum morbidity. It must be emphasized that the degree of
      prostatic enlargement or the severity of the symptoms does not indicate clinical
      success or failure. However, the degree of bladder outflow obstruction and the
      quality of treatment achieved are very important: a) In patients with severe
      obstruction, TURP or open surgery continues to be the treatment that affords
      rapid relief of their symptoms. b) The clinical response to TUMT is dose
      dependent; i.e., higher thermal dose, longer session (2 h) and the use of
      different catheters enhance the therapeutic efficacy.

PMID- 7524451
TI  - Antigen specificity of antihistone antibodies in localized scleroderma.
AB  - BACKGROUND AND DESIGN: Recently, we detected antihistone antibodies (AHAs) in
      patients with localized scleroderma. However, the exact antigen specificity of
      AHAs in this disease is still unknown. Therefore, we determined the reactivity of
      AHAs with five individual histones and the correlation of AHAs with rheumatoid
      factor in localized scleroderma by means of enzyme-linked immunosorbent assay.
      Twenty patients with localized scleroderma who had IgG and/or IgM AHAs, as
      determined by enzyme-linked immunosorbent assay, were examined. These patients
      were classified into the following three subgroups: patients with generalized
      morphea (n = 11), patients with linear scleroderma (n = 6), and patients with
      morphea (n = 3). RESULTS: In generalized morphea, IgG AHAs strongly reacted with
      histones H1, H2A, and H2B; and IgM AHAs strongly reacted with H1 and H2B, as
      determined by means of enzyme-linked immunosorbent assay. The pattern of
      reactivity in linear scleroderma and morphea was similar to that in generalized
      morphea. A homogeneous immunofluorescent pattern on HEp-2 cells, which was
      produced by localized scleroderma sera, was completely abolished by absorption
      with total histones. By employing a latex agglutination test, IgM rheumatoid
      factor was detected in 60% of the 20 patients with localized scleroderma and at a
      frequency of 82% in those with generalized morphea. However, an absorption test
      of rheumatoid factor activity with human IgG revealed no cross-reactivity of AHAs
      with rheumatoid factor. CONCLUSIONS: Our data suggest that AHAs in localized
      scleroderma are directed against native chromatin, since H1, H2A, and H2B occupy
      a relatively exposed portion of chromatin.

PMID- 7524447
TI  - 3-Methylcholanthrene-mediated induction of cytochrome P4501A2 in human hepatoma
      HepG2 cells as quantified by the reverse transcription-polymerase chain reaction.
AB  - The feasibility of using HepG2 human hepatoma cells to study the regulation of
      the expression of the cytochrome P4501A2 gene (CYP1A2) was examined. The reverse
      transcription-polymerase chain reaction (RT-PCR) assay revealed that HepG2 cells
      constitutively express CYP1A2 and are able to respond to 3-methylcholanthrene
      (3MC) by an induction of CYP1A2 mRNA. In these studies, selected sequences from
      intron-exon junctions were used as mRNA-specific primers for both CYP1A2 and the
      beta-actin gene. The level of induction was quantitated based on two parameters
      within the exponential phase of the amplification: the difference in the number
      of cycles that yields the same level of amplification and the efficiency of the
      PCR reaction. Using this method, it was estimated that the CYP1A2 steady-state
      mRNA level increased to a maximum of 12-fold at 24 h after exposure of the cells
      to 3MC. Both a reduction in basal expression as well as an increased accumulation
      of CYP1A2 mRNA appeared responsible for the overall induction at 24 and 48 h.
      These results suggested that the HepG2 cell line would be appropriate for
      studying the regulation of CYP1A2 expression.

PMID- 7524452
TI  - Methyl tertiary butyl ether in human blood after exposure to oxygenated fuel in
      Fairbanks, Alaska.
AB  - Residents of Fairbanks, Alaska reported health complaints when 15%, by volume,
      methyl tertiary butyl ether (MTBE) was added to gasoline during an oxygenated
      fuel program. We conducted an exposure survey to investigate the effect of the
      program on human exposure to MTBE. We studied 18 workers in December 1992 during
      the program and 28 workers in February 1993 after the program was suspended. All
      workers were heavily exposed to motor vehicle exhaust or gasoline fumes. In
      December, the median post-shift blood concentration of MTBE in the workers was
      1.8 micrograms/l (range, 0.2-37.0 micrograms/l), and in February the median post
      shift blood concentration of MTBE in the 28 workers was 0.24 micrograms/l (range,
      0.05-1.44 micrograms/l; p = .0001). Blood MTBE levels were measurably higher
      during the oxygenated fuel program in Fairbanks than after the program was
      suspended.

PMID- 7524454
TI  - Local resection of the head of the pancreas combined with longitudinal
      pancreaticojejunostomy in the management of patients with chronic pancreatitis.
AB  - OPERATION: Local resection of the head of the pancreas combined with longitudinal
      pancreaticojejunostomy of the body and tail of the pancreas (LR-LPJ) was designed
      to improve decompression of the head of the pancreas, which often was not drained
      well by standard longitudinal pancreaticojejunostomy. This was achieved by
      excising the head of the pancreas overlying the ducts of Wirsung and Santorini,
      and duct to the uncinate, along with their tributary ducts. PATIENT MATERIAL: The
      operation has been performed on 50 patients. There were five late deaths among
      the 50 patients; two at 6 months, and one each at 24, 26, and 91 months. Eighty
      percent of the patients were alcoholics, 50% had pseudocysts, and 80% had
      calcification. ASSESSMENT: Pain was assessed on a scale of 1 to 10, with 10 being
      most severe. Narcotic intake was considered minimal-Vicodin equivalent
      (hydrocodone bitartate, 5 mg, acetaminophen, 500 mg; Vicodin, Knoll
      Pharmaceuticals, Whippany, NJ) once or twice/month; moderate--Vicodin weekly
      daily; and major--meperidine hydrochloride (Demerol, Winthrop Pharmaceuticals,
      New York, NY) weekly or daily. RESULTS: Pain relief in 47 patients was excellent
      (74.5%), improved in 12.75%, and unimproved in 12.75%. Endocrine status in 45
      patients was as follows: 69% were not diabetic, and 20% were diabetic
      preoperatively and postoperatively. Postoperatively, 11% had progression of their
      diabetes. Exocrine function was not worsened and may have been improved in some
      patients. Sixty-four percent of 39 patients gained an average of 15.3 pounds.
      Fifty-nine percent of patients were not working preoperatively or
      postoperatively. CONCLUSIONS: The LR-LPJ provides good pain relief with a modest
      increase in endocrine and exocrine insufficiency and a significant increase in
      weight. Even when relieved of pain, patients seldom return to the work force.

PMID- 7524455
TI  - Pelvic resection of recurrent rectal cancer.
AB  - OBJECTIVE: The authors describe their experience with pelvic resection of
      recurrent rectal cancer with emphasis on patient selection for curative intent
      based on known tumor risk factors. SUMMARY BACKGROUND DATA: Pelvic recurrence is
      a formidable problem in 30% of patients who have undergone a curative resection
      of primary rectal cancer. Although radiation can reduce the development of local
      recurrence and can provide palliation to many patients with localized disease, it
      is not curative. The authors and others have used the technique of abdominal
      sacral resection (ABSR) with or without pelvic exenteration to resect pelvic
      recurrence and its musculoskeletal extensions in selected patients with
      satisfactory long-term survival. METHODS: The technique of ABSR with or without
      pelvic exenteration or resection of pelvic viscera, which the authors have
      described previously, was used in 53 patients with recurrent rectal cancer--47
      patients for curative intent and 6 for palliation. Previous surgeries were
      abdominal perineal resections (APRs) in 26 patients, anterior resections in 19
      patients, and other procedures in 2 patients; original primary Dukes' stage was B
      in 52% and C in 48%. Almost all patients had been irradiated previously,
      generally in the 4000 to 5900 cGy range. Preoperative carcinoembryonic antigen
      (CEA) levels (before ABSR) were elevated (> 5 ng/mL) in 54%. RESULTS:
      Postoperative morbidity was encountered in most patients. Mortality was 8.5% in
      the curative group. Long-term survival for 4 years was achieved in 14 of 43
      patients (33%), and 10 patients were alive with an acceptable quality of life
      after 5 years. Patients who had previous anterior resections or whose
      preoperative CEA levels were less than 10 ng/mL had a survival rate of
      approximately 45%, whereas patients with previous APRs and preoperative CEA
      levels greater than 10 ng/mL had a survival rate of only 15% to 18%. Patients
      with bone marrow invasion, positive margins, or pelvic node metastases had a
      median survival of only 10 months. CONCLUSIONS: Pelvic recurrence of rectal
      cancer can be resected safely with expectation of long-term survival of 33%.
      Patient selection based on known risk factors can identify patients most likely
      to benefit from resection and eliminate those who should be treated for
      palliation only.

PMID- 7524459
TI  - Management of tracheal and bronchial stenoses with the Gianturco stent.
AB  - Thirty-six cancer patients with symptomatic tracheobronchial stenoses received
      Gianturco tracheobronchial stents over a 9-year period. Symptoms improved in 28
      patients (78%). The overall median survival was 1 month 3 weeks (range, 4 days to
      35 months). The median survival for patients who showed improvement after
      receiving stents was 3 months compared with 1 week for those who did not respond.
      Complications were minimal. The Gianturco stent may palliate symptoms of
      tracheobronchial compression in selected cancer patients.

PMID- 7524457
TI  - Topical aprotinin in cardiac operations.
AB  - We performed a prospective, randomized, double-blind trial of topical aprotinin
      versus placebo in 100 patients undergoing cardiac operations with cardiopulmonary
      bypass. Fifty-five patients received aprotinin. Forty underwent coronary artery
      bypass grafting (CABG) and 15 valve replacement +/- CABG. Of 45 patients in the
      control group 38 underwent CABG and 7 valve replacement +/- CABG. Aprotinin (50
      mL; 70 mg) or placebo was applied topically to the heart, pericardium, and
      mediastinum before sternal closure. There were five reentries for bleeding with a
      surgical site identified in four. Mean blood loss was significantly less in the
      aprotinin group (653 versus 903 mL; p = 0.002), and fewer aprotinin patients
      received blood as a volume expander (67.5% versus 88%; p = 0.03). In coronary
      patients alone when aspirin administration was continued until the day of
      operation there was no difference between treatment and placebo groups (768
      versus 879 mL). When aspirin administration was discontinued 2 weeks before
      operation there was a significant difference (558 versus 884 mL; p = 0.016) as in
      the group overall. This provides the potential for intrapericardial instillation
      for patients with excessive postoperative bleeding.

PMID- 7524456
TI  - Monitoring of anticoagulation in aprotinin-treated patients during heart
      operation.
AB  - Since aprotinin has become extensively used during cardiopulmonary bypass the
      maintenance of safe anticoagulation is a concern. Aprotinin affects
      anticoagulation measurement by the activated clotting time. Therefore, a reliable
      new measurement is needed to monitor anticoagulation during cardiopulmonary
      bypass. In the present study, we tested the efficacy of two alternative
      measurements in which whole blood clotting was stimulated by high-dose
      thromboplastin or by high-dose thrombin. During cardiopulmonary bypass under
      standardized heparinization, the activated clotting time was twofold longer in
      the aprotinin group than in control group (p < 0.05), whereas high-dose
      thromboplastin and high-dose thrombin groups were not significantly affected by
      aprotinin. In laboratory tests using blood from healthy volunteers, all methods
      showed linear correlation with heparin concentration in the absence of aprotinin
      (p < 0.05). However, the activated clotting time measurement was prolonged more
      by heparin when aprotinin was present (p < 0.05), whereas high-dose
      thromboplastin and high-dose thrombin measurements were not. Moreover, these
      measurements were faster and more dependable than the activated clotting time.
      Therefore, high-dose thromboplastin time and high-dose thrombin time seem to be
      reliable for monitoring anticoagulation when aprotinin is used during
      cardiopulmonary bypass.

PMID- 7524458
TI  - Associated primary esophageal and lung carcinoma: a study of 39 patients.
AB  - From 1979 to 1992, of 1,294 patients with esophageal squamous cell carcinoma, 39
      patients (3.2%) (38 male patients, 1 female patient; mean age, 58 years) had
      associated primary lung carcinoma. Criteria for the diagnosis of primary lung
      carcinoma were: (1) non-squamous cell carcinoma tumors, (2) tumors existing
      before the esophageal squamous cell carcinoma, and (3) solitary squamous cell
      carcinoma presenting with endobronchial involvement. The two tumors were observed
      synchronously in 22 patients (56%) and metachronously in 17, with a mean tumor
      free interval of 46 months (range, 18 to 77 months). In patients with synchronous
      disease, 10 underwent nonoperative treatment or a palliative surgical procedure,
      and 12 (55%) underwent a curative operation. In patients with metachronous
      disease, a curative operation was performed in all for the first tumor and in 9
      (53%) for the second tumor. The overall postoperative mortality rate was 15%. Two
      patients (10%) died after the curative operation. None of the patients died who
      underwent curative esophagectomy combined with lobectomy. For the patients with
      synchronous disease, the 5-year survival rate was 11% in those who underwent a
      curative operation, and the longest survival in those who received palliative
      treatment was 18 months. For the patients with metachronous disease, the 5-year
      survival rates from the date of the diagnosis of the second tumor were 17% for
      those who had a curative operation and 11% for those who received palliative
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524461
TI  - [Electrocardiographic aspects of sinoatrial block].
AB  - There are many electrocardiographic changes in sinoatrial block. Only 2nd and 3rd
      degree blocks can be analysed on surface recordings. However, they manifest
      themselves by pauses, the descriptions of which are rich and varied. They also
      vary according to the circumstances of apparition and the escape rhythms which
      accompany them. Related ECG changes such as chronotropic insufficiency or carotid
      sinus syndrome have been described. However, their significance is not univocal
      and only a precise analysis of the ECG recordings allows correct interpretation
      of the clinical and paraclinical signs and the institution of appropriate
      therapy.

PMID- 7524460
TI  - Aprotinin preserves hemostasis in aspirin-treated patients undergoing
      cardiopulmonary bypass.
AB  - Various clinical trials have shown that hemostasis is improved by the
      administration of aprotinin during cardiopulmonary bypass. However, this effect
      has not been proved for those patients treated preoperatively with aspirin.
      Therefore, a double-blind, placebo-controlled study was conducted to test the
      efficacy of low-dose aprotinin (2 x 10(6) KIU in the pump prime solution) in
      preserving hemostasis in 40 aspirin-treated (325 mg) patients undergoing coronary
      artery bypass grafting. Aprotinin brought about a decrease in the postoperative
      blood loss (p < 0.05). The in vitro bleeding test (Thrombostat) demonstrated that
      aprotinin preserved the platelet hemostatic function in aspirin-treated patients
      during cardiopulmonary bypass (p < 0.05). The inhibitory effects of aspirin on
      collagen-induced platelet aggregation and thromboxane production were not
      influenced by aprotinin treatment. The findings from the present study indicate
      that aprotinin preserves hemostasis in aspirin-treated patients during
      cardiopulmonary bypass, but aspirin's effect on platelets is maintained.
      Therefore, aprotinin seems to be a useful adjunct treatment in aspirin-treated
      patients undergoing coronary artery bypass grafting.

PMID- 7524462
TI  - Elevated cerebrospinal fluid levels of oxytocin in obsessive-compulsive disorder.
      Comparison with Tourette's syndrome and healthy controls.
AB  - BACKGROUND: Limited neurobiological data have implicated central arginine
      vasopressin in the pathobiology of obsessive-compulsive disorder (OCD). Based on
      twin, family genetic, and pharmacological studies, some forms of OCD are
      etiologically related to Tourette's syndrome. The role of arginine vasopressin
      and related compounds such as oxytocin in Tourette's syndrome has not been
      previously explored. METHODS: To compare cerebrospinal fluid (CSF) levels of
      arginine vasopressin and oxytocin, we collected CSF at midday in a standardized
      fashion from a total of 83 individuals (29 patients with OCD, 23 patients with
      Tourette's syndrome, and 31 normal controls). We also collected family study data
      on each subject to determine which subjects had a family history positive for
      Tourette's syndrome, OCD, or related syndromes. RESULTS: In contrast to previous
      reports, we report similar concentrations of arginine vasopressin for all three
      groups but increased oxytocin levels in patients with OCD. Remarkably, this
      increase was observed only in a subset of patients with OCD (n = 22)
      independently identified as being without a personal or family history of tic
      disorders (P = .0003). In this subgroup of patients, the CSF oxytocin level was
      correlated with current severity of OCD (n = 19, r = .47, P < .05). CONCLUSIONS:
      A possible role for oxytocin in the neurobiology of a subtype of OCD is suggested
      by the elevated CSF levels of oxytocin and by the correlation between CSF
      oxytocin levels and OCD severity. These findings reinforce the value of family
      genetic data in identifying biologically homogeneous (and perhaps more
      etiologically homogeneous) groups of patients with OCD. Together with emerging
      pharmacological data showing differential responsiveness to treatment of tic
      related OCD vs non-tic-related OCD, these data also argue strongly for the
      incorporation of tic-relatedness as a variable in biological and behavioral
      studies of patients with OCD.

PMID- 7524464
TI  - Detection of proliferating cell nuclear antigen in paraffin-embedded specimens is
      dependent on preembedding tissue handling and fixation.
AB  - Immunohistochemical detection of proliferating cell nuclear antigen (PCNA), a
      cell cycle-related protein used to estimate tumor growth fraction, is variable in
      formalin-fixed compared with methanol-fixed tissue specimens. This is assumed to
      result from conformational changes in the antigenic epitope induced by
      formaldehyde; therefore, to be susceptible to retrieval in archival specimens. In
      this study, formalin fixation reduced the intensity of staining and the number of
      positive cells to approximately 25% of those in methanol-fixed material. The
      washing of tissue specimens prior to methacarn fixation also reduced PCNA
      staining. Loss of staining was not restored after use of a commercial retrieval
      kit recommended for PCNA immunohistochemistry. Immunoblotting of formalin
      fixatives and saline washings after removal of tissue specimens consistently
      demonstrated the presence of PCNA-like activity in solution. We conclude that the
      exceptional solubility of PCNA is responsible for reduced immunostaining in
      formalin-fixed material, that the loss is irreversible, and that methanol or
      methacarn is the fixative of choice for PCNA immunohistochemistry.

PMID- 7524465
TI  - Extramedullary hematopoiesis during therapy with granulocyte colony-stimulating
      factor.
AB  - Granulocyte colony-stimulating factor is a glycoprotein that promotes the
      proliferation and differentiation of neutrophils. It also results in an increase
      in circulating hematopoietic progenitor cells. We describe two cases of
      extramedullary hematopoiesis in patients receiving granulocyte colony-stimulating
      factor with chemotherapy for metastatic breast cancer.

PMID- 7524463
TI  - Changes in cerebrospinal fluid neurochemistry during treatment of obsessive
      compulsive disorder with clomipramine.
AB  - BACKGROUND: This study examined the effect of long-term (mean, 19 months)
      treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of
      several neuropeptides and monoamine metabolites in children and adolescents with
      obsessive-compulsive disorder. METHODS: The CSF levels of corticotropin-releasing
      hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites
      5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4
      hydroxyphenylglycol were measured in 17 children and adolescents with obsessive
      compulsive disorder before and after long-term treatment with clomipramine.
      RESULTS: Treatment resulted in significant decreases in CSF levels of
      corticotropin-releasing hormone (mean +/- SD, 175 +/- 32 vs 152 +/- 25 pmol/L, P
      < .03) and vasopressin (mean +/- SD, 1.30 +/- 0.57 vs 0.86 +/- 0.54 pmol/L, P <
      .02) and a trend toward a decrease in somatostatin levels (mean +/- SD, 21.3 +/-
      8.5 vs 15.3 +/- 9.8 pmol/L, P < .06). Treatment also significantly increased CSF
      oxytocin levels (mean +/- SD, 6.05 +/- 1.60 vs 6.70 +/- 1.44 pmol/L, P < .01).
      Significant changes in CSF monoamine metabolite levels with treatment included
      significant decreases in CSF levels of 5-hydroxyindoleacetic acid (mean +/- SD,
      109 +/- 31 vs 77 +/- 23 pmol/mL, P < .001), CSF homovanillic acid (mean +/- SD,
      273 +/- 111 vs 237 +/- 101 pmol/mL, P < .04), and 3-methoxy-4-hydroxyphenylglycol
      (mean +/- SD, 42.4 +/- 10.2 vs 36.1 +/- 4.8 pmol/L, P < .02) and a significant
      increase in the homovanillic acid-5-hydroxyindoleacetic acid ratio (mean +/- SD,
      2.44 +/- 0.46 vs 3.42 +/- 0.84, P < .0001). CONCLUSIONS: These neuropeptide
      results coupled with evidence that central administration of corticotropin
      releasing hormone, vasopressin, and somatostatin to laboratory animals increases
      arousal and acquisition of conditioned behaviors whereas central administration
      of oxytocin has opposite behavioral effects are consistent with a role for these
      neuropeptides in the pathophysiologic processes and pharmacologic treatment of
      obsessive-compulsive disorder.

PMID- 7524467
TI  - [An evaluation of the plastic function of the cardiomyocytes by silver staining
      of the nucleoli in patients operated on for ischemic heart disease].
AB  - Examinations of plastic function changes in myocardial cells (MC) from 36
      patients with chronic ischemic heart disease were carried out before, during and
      soon after cardioplegic ischemia. The initial mean number of silver grains in
      nucleoli varied greatly showing some difference between groups of the patients
      with (9.5 +/- 0.48) or without (11.0 +/- 0.5) myocardial infarction. During the
      myocardial arrest this index of MC plastic activity was decreased in all but 7
      patients. In contrast to this, it was elevated in most patients tested during
      subsequent reperfusion. On the basis of these data and parallel histochemical
      photometric assessment of DNA, RNA and succinate dehydrogenase activity, a
      hypothesis was suggested which explains the non-standard elevation of ribosomal
      cistron activity during both myocardial arrest and reperfusion by their
      compensatory reaction to myocardial injury.

PMID- 7524469
TI  - Immunohistochemical demonstration of bcl-2 protein in human tooth germs.
AB  - This study sought to detect patterns of bcl-2 protein expression that could
      provide more insight into the cellular dynamics of tooth development. As bcl-2
      serves to prevent cell death, its occurrence in odontogenic tissues might be
      helpful in identifying cell populations from which odontogenic tumours may arise.
      The bcl-2 protein was found only in the epithelial part of the tooth germ and was
      present in all parts of the enamel organ except the ameloblast. This suggests
      that bcl-2 protein plays a part in maintaining the viability of the enamel organ.
      The presence of bcl-2 in the fully matured tooth germ and adjacent dental lamina
      might indicate that epithelial odontogenic tumours may originate from various
      parts of the enamel organ.

PMID- 7524468
TI  - Anti-myelin basic protein and anti-proteolipid protein antibody-secreting cells
      in the cerebrospinal fluid of patients with acute optic neuritis.
AB  - OBJECTIVE: To study the intrathecal synthesis of anti-myelin basic protein (MBP)
      and anti-proteolipid protein (PLP) antibodies in patients in the early stages of
      multiple sclerosis. DESIGN AND SETTING: A study of consecutive patients with
      acute optic neuritis (ON) who were undergoing lumbar punctures in an ambulatory
      unit. PATIENTS: Eleven patients with acute idiopathic ON and 14 patients with
      acute ON as a symptom of definite multiple sclerosis (the diagnosis of which was
      supported by clinical or laboratory findings). Nineteen patients with other
      neurological diseases (10 with inflammatory diseases) served as controls. MAIN
      OUTCOME MEASURES: Numbers of anti-MBP and anti-PLP antibody-secreting cells in
      peripheral blood and cerebrospinal fluid samples that were enumerated with an
      immunospot assay. RESULTS: Cerebrospinal fluid cells that secreted anti-MBP or
      anti-PLP antibodies were detected in 10 of 15 and in 21 of 23 patients with acute
      ON, while they were detected in nine of 18 and in six of 18 patients with other
      neurological diseases, respectively. Patients with ON had significantly more anti
      PLP-secreting cells than did patients with other neurological diseases (P < .01).
      No difference was observed for anti-MBP-secreting cells. A significant
      correlation between the time from onset and the number of anti-PLP-secreting
      cells was found in patients with idiopathic ON (P < .02). CONCLUSIONS: These data
      suggest that anti-PLP antibodies are a more specific finding in demyelinating
      disease than anti-MBP antibodies. Furthermore, they suggest that anti-PLP
      antibodies may arise as a consequence of the demyelinating process.

PMID- 7524470
TI  - Influence of atrial natriuretic peptide on cyclic nucleotides and amylase release
      in rat parotid salivary gland in vitro.
AB  - Atrial natriuretic peptide (ANP), sodium nitroprusside and hydroxylamine
      increased cGMP accumulation in rat parotid acinar cells both in the presence and
      absence of forskolin but in a different manner. On the other hand, ANP decreased
      forskolin-stimulated cAMP accumulation, although sodium nitroprusside and
      hydroxylamine had no effect on cAMP accumulation. Amylase release stimulated by
      forskolin, dibutyryl-cAMP or isoproterenol was depressed by ANP, whereas sodium
      nitroprusside and hydroxylamine did not evoke the inhibition of forskolin
      stimulated amylase release. These results suggest that the inhibition of cAMP
      accumulation and of amylase release by ANP were not mediated via cGMP produced by
      guanylate cyclase-A.

PMID- 7524471
TI  - Pancreatic biopsy in normal cats.

PMID- 7524472
TI  - Radiotherapy in the treatment of malignant mesothelioma of the pleura, with
      special reference to its use in palliation.
AB  - Most patients presenting with malignant mesothelioma of the pleura (MMP) are only
      suitable for palliative treatment. Radiotherapy has not been shown to improve
      survival in patients with this disease, but is of use in the palliation of
      symptoms. In this retrospective review of 111 patients with MMP referred to the
      Peter MacCallum Cancer Institute, the palliative effect of radiotherapy was
      analysed. More than half of the patients whose response could be assessed had
      some symptomatic relief from the radiotherapy treatment. No dose-response
      relationship could be found.

PMID- 7524466
TI  - Antibodies against linear and conformational epitopes of the human papillomavirus
      (HPV) type 16 E6 and E7 oncoproteins in sera of cervical cancer patients.
AB  - Sera obtained from 137 cervical cancer patients were analysed for the presence of
      antibodies to the human papillomavirus (HPV) type 16 proteins E6 and E7 by the
      aid of different assays, i.e. ELISA using as antigen either synthetic peptides or
      the complete E7 protein and radio-immunoprecipitation (RIPA) which uses the viral
      protein made by in vitro transcription/translation. In agreement with previous
      reports, reactivity to the E7 protein was found more frequently than to the E6
      protein (31.4% vs. 16.8%) when the sera were assayed by peptide-based ELISA. In
      contrast, when RIPA was employed, reactivity to either protein was obtained at
      similar frequency (38.7% vs 46.7%). When the protein was denatured prior to
      immuno-precipitation the reactivity was lost in all sera tested for E6-specific
      antibodies but only in a few samples in the E7-RIPA. Therefore it was concluded
      that the increased sensitivity of the E6-RIPA as compared to the E6 peptide-ELISA
      is due to the detection of antibodies to conformational epitopes which are
      presented by the in vitro product but not by the synthetic peptides. Eighty-two
      sera from healthy donors were tested by HPV 16E6- and E7-RIPA and also by ELISA
      using the HPV 16E7 protein which was produced in the fission yeast
      Schizosaccharomyces pombe. One sample reacted each in the E6- and E7-RIPA
      indicating a high specificity of these assays. The E7 protein-ELISA proved to be
      less sensitive for the detection of antibodies in cervical cancer patients' sera
      (22.6% positive) as compared to peptide-based ELISA or RIPA.

PMID- 7524474
TI  - Iron requirement for cellular DNA damage and growth inhibition by hydrogen
      peroxide and bleomycin.
AB  - Studies with Euglena gracilis and HL-60 cells have assessed the need for
      intracellular iron in the mechanisms of inhibition of cell growth and DNA damage
      by H2O2 and bleomycin. Cell culture media were directly depleted of iron in order
      to deprive cells of nutrient iron. Major pools of cellular iron were reduced in
      both cell types. Nevertheless, iron bound in e.s.r.-observable haem protein and
      ribonucleotide diphosphate reductase in HL-60 cells was not decreased. In both
      control cell populations, there was a concentration-dependent reduction in
      proliferation and cell survival caused by H2O2. In comparison, the proliferation
      rates of both iron-deficient cell types were significantly less sensitive to
      H2O2. H2O2 caused concentration-dependent single-strand breakage in DNA in
      control HL-60 and Euglena gracilis cells. Iron deficiency reduced the amount of
      strand breaks in HL-60 cells at each concentration of H2O2 used. Single-strand
      breakage caused by H2O2 in Euglena gracilis was a direct function of the
      concentration of iron in which the cells had been grown. Growth inhibition and
      both single- and double-strand DNA damage caused by bleomycin were substantially
      reduced or eliminated in iron-deficient cells. Copper bleomycin behaved like
      metal-free bleomycin when assayed for the capacity to cause DNA damage in iron
      normal and iron-deficient HL-60 cells. In contrast, iron bleomycin was equally
      active under the two conditions in these cells.

PMID- 7524473
TI  - Hyperlipidemic endothelial injury and angiogenesis.
AB  - Hypercholesterolemia is associated with endothelial cell dysfunction which may in
      part be related to an accumulation of toxic lipoprotein degradation products in
      artery walls. Oxidized low-density lipoprotein (LDL) and its products have been
      incriminated in impairing various endothelial functions including G-protein
      dependent transmembrane signaling, calcium regulation, phosphoinositide turnover,
      protein kinase C activation and others. Modification of such cell regulatory
      functions may alter the responsiveness of endothelial cells to angiogenic
      (mitogenic) stimuli. Endothelial cell replication is necessary for the growth of
      preexisting arterial channels and the formation of new microvessels
      (angiogenesis). Experiments in intact rabbits indicate that endothelial
      replication necessary for vascular growth is markedly impaired in the presence of
      hypercholesterolemia, a defect that could play an important role in the
      pathophysiology of occlusive atherosclerotic disease.

PMID- 7524476
TI  - Down-regulation of the c-myc proto-oncogene in inhibition of vascular smooth
      muscle cell proliferation: a signal for growth arrest?
AB  - Vascular smooth muscle (VSM) cell proliferation contributes to the pathogenesis
      of atherosclerosis, restenosis after angioplasty and vein graft disease. The
      regulation of genes involved in VSM cell proliferation, particularly by naturally
      occurring inhibitors, is therefore of some importance. We have investigated the
      role of the c-myc proto-oncogene in growth arrest of exponentially proliferating
      rat VSM cells, following mitogen withdrawal, treatment with heparin (50
      micrograms/ml), interferon-gamma (IFN-gamma) (100 i.u./ml), or the cyclic
      nucleotide analogues, 8-bromo-adenosine-3'5'-cyclic monophosphate (8-Br-cAMP; 0.1
      mM) and 8-bromoguanosine-3'5'-cyclic monophosphate (8-Br-cGMP; 0.1 mM). Growth
      arrest was accompanied by down-regulation of c-Myc protein and mRNA following
      treatment with all inhibitors. Serum withdrawal or IFN-gamma treatment suppressed
      c-myc expression by more than 50% within 2 h, and this occurred throughout the
      cell cycle. Platelet-derived growth factor, epidermal growth factor and basic
      fibroblast growth factor all contributed independently to the maintenance of c
      myc expression. Heparin, 8-Br-cAMP or 8-Br-cGMP also suppressed c-myc, but this
      occurred later, after 24-48 h, and was also observed following arrest by
      metabolic block. We conclude that c-myc expression is linked to VSM cell growth
      arrest in response to endogenous regulators and metabolic block. Down-regulation
      of c-myc expression may thus be an essential part of the arrest programme in VSM
      cells induced by many pharmacological agents.

PMID- 7524475
TI  - Shear-stress-induced von Willebrand factor binding to platelets causes the
      activation of tyrosine kinase(s).
AB  - Pathological arterial blood flow generates fluid shear stresses that directly
      cause platelet aggregation. The mechanism of shear-induced platelet aggregation
      is incompletely understood, but involves von Willebrand factor (vWF) binding to
      platelet glycoprotein (GP) Ib and GP IIb-IIIa, leading to the transmembrane
      influx of Ca2+ and the activation of protein kinase C. To investigate this
      further, shear-stress-induced protein tyrosine phosphorylation (PTP) of washed
      platelets was studied in a cone-plate viscometer. A time- and shear-stress
      dependent tyrosine phosphorylation of substrates with approx. M(r) 29,000-31,000,
      36,000, 50,000, 58,000, 64,000, 76,000, 85,000 and 105,000 was observed. PTP in
      response to a threshold shear stress of 0.3 mN/cm2 (30 dyn/cm2) was enhanced in
      most cases by exogenous purified human vWF, and PTP in response to a pathological
      shear stress of 0.9 mN/cm2 (90 dyn/cm2) was inhibited in some cases by inhibiting
      vWF binding to GP Ib or GP IIb-IIIa, or by inhibiting Ca2+ responses with
      extracellular EGTA. Shear-induced PTP of a substrate of M(r) approximately 31,000
      appeared to be independent of GP Ib, and PTP of a substrate(s) of M(r)
      approximately 29,000 was shear-stress-dependent but independent of extracellular
      Ca2+. Cytochalasin D, which inhibits GP Ib-cytoskeleton interactions, inhibits
      the PTP of a substrate of M(r) approximately 76,000. These results suggest that
      tyrosine phosphorylation may be involved in transmembrane signalling that
      mediates platelet adhesion and aggregation in response to pathological shear
      stresses generated at sites of arterial vaso-occlusion.

PMID- 7524477
TI  - Rapid and efficient purification of Src homology 2 domain-containing proteins:
      Fyn, Csk and phosphatidylinositol 3-kinase p85.
AB  - To analyse the regulation of Src family tyrosine kinases in vitro, we have
      purified Fyn and Csk, a kinase capable of regulating Fyn activity by
      phosphorylation, from baculovirus-infected insect cells. The proteins were
      purified by affinity purification over a phosphotyrosine column. Highly purified
      proteins were eluted from the resin by a salt gradient and further purified by
      ion-exchange chromatography. This purification scheme was successfully applied to
      a third, unrelated protein that also contains the Src homology 2 (SH2) domain,
      namely the 85 kDa subunit of phosphatidylinositol 3-kinase, indicating that this
      method is versatile and should prove applicable to any protein with an accessible
      SH2 domain. The binding of Csk to different phosphopeptides was tested, and
      specificity for the autophosphorylation site of Fyn was demonstrated. Pure Csk
      was used to phosphorylate Fyn and down-regulate its kinase activity, and the
      kinetic parameters of both the active and the repressed forms of Fyn were
      determined. Repression of Fyn activity by Csk reduced binding of Fyn to
      phosphopeptides to undetectable levels, supporting the model that predicts an
      intramolecular interaction of the Fyn SH2 domain with a C-terminal
      phosphotyrosine residue.

PMID- 7524480
TI  - The hemispheric functional expression of the thyrotropin-releasing-hormone
      receptor is not determined by the receptors' physical distribution.
AB  - The thyrotropin-releasing-hormone receptor (TRH-R) is a member of a family of the
      G-protein-coupled receptors that share structural similarities and exert their
      physiological action via the inositol lipid signal-transduction pathway. The TRH
      R when expressed in Xenopus oocytes exhibits marked preference of the response
      (increased chloride conductance) for the animal hemisphere. Whereas the rat TRH-R
      functional distribution was strongly asymmetric (animal/vegetal ratio = 9.5), the
      mouse TRH-R exhibited a significantly lower ratio (3.9). Truncation of the last
      59 amino acids of the C-terminal region of the mouse TRH-R did not lead to any
      changes in the functional hemispheric distribution. Despite the polarization of
      response, receptor number was similar on both hemispheres. Moreover, the apparent
      half-life of the functional expression of the TRH-R was approx. 4 h on both
      hemispheres when the expression was inhibited by a specific antisense
      oligonucleotide. Inhibition of total protein synthesis with cycloheximide
      affected hemispheric responses mediated by each of the three TRH-Rs tested in a
      qualitatively different way. These results suggest that an additional, rapidly
      degraded, protein modulates the functional hemispheric expression of the TRH-Rs.

PMID- 7524478
TI  - Stimulatory effect of pervanadate on calcium signals and histamine secretion of
      RBL-2H3 cells.
AB  - We examined the effect of pervanadate on the activation of rat basophilic
      leukaemia (RBL-2H3) cells. The pervanadate, generated from a combination of H2O2
      and vanadate (Vi), induced concomitantly protein tyrosine phosphorylation,
      formation of inositol 1,4,5-trisphosphate (IP3), an increase in [Ca2+]i, and
      histamine secretion in RBL-2H3 cells. These effects were clearly dependent on the
      ratio of H2O2/Vi. The secretion of histamine, IP3 formation, and sustained
      increase in [Ca2+]i were effectively induced by treatment of the cells with the
      pervanadate produced from 1 mM H2O2 and 1 mM Vi. These effects mimic the
      stimulatory effects of an antigen (dinitrophenylated BSA) on Ca2+ signals,
      histamine secretion and morphological changes. Protein tyrosine phosphorylation,
      formation of IP3 and transient increase in [Ca2+]i were markedly induced by the
      pervanadate produced from 3 mM H2O2 and 1 mM Vi. However, histamine secretion
      induced by the pervanadate was very low. After the pervanadate from 3 mM H2O2 and
      1 mM Vi was treated with catalase, it was able to induce the [Ca2+]i increase and
      histamine secretion as much as the antigen did. This indicates that pervanadate
      from a lower H2O2 concentration (1 mM H2O2/1 mM Vi) and catalase-treated
      pervanadate from a higher H2O2 concentration (3 mM H2O2/1 mM Vi) are able to
      mimic the activity that was caused by cross-linking of IgE receptors with
      antigen. The present results also demonstrate that protein tyrosine
      phosphorylation seems to have a crucial role in Ca2+ entry from the external
      medium, and that a sustained [Ca2+]i increase is an important step for histamine
      secretion in RBL-2H3 cells.

PMID- 7524479
TI  - Effects of aniso-osmolarity and hydroperoxides on intracellular pH in isolated
      rat hepatocytes as assessed by (2',7')-bis(carboxyethyl)-5(6)-carboxyfluorescein
      and fluorescein isothiocyanate-dextran fluorescence.
AB  - Freshly isolated rat hepatocytes were plated for 4-6 h and either loaded with
      (2',7)-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) or allowed to endocytose
      fluorescein isothiocyanate (FITC)-coupled dextran in order to study the effects
      of aniso-osmotic exposure and oxidative stress on cytosolic (pHcyt) and apparent
      vesicular pH (pHves) by single-cell fluorescence recordings. In the presence of
      normo-osmotic (305 mosmol/l) medium pHcyt was 7.23 +/- 0.03 (n = 108), whereas an
      apparent pH of 6.07 +/- 0.02 (n = 156) was found in the vesicular compartment
      accessible to endocytosed FITC-dextran. Substitution of 60 mM NaCl against 120 mM
      raffinose had no effect on pHcyt or apparent pHves, whereas addition of NH4Cl
      increased both pHcyt and apparent pHves. Hypo-osmotic cell swelling lowered
      pHcyt, whereas simultaneously apparent pHves increased. These effects were
      rapidly reversible upon re-institution of normo-osmotic media. Similarly, an
      increase of apparent pHves was observed when cell swelling was induced by Ba2+,
      glutamine or histidine. Conversely, hyperosmotic cell shrinkage due to addition
      of NaCl or raffinose led to a cytosolic alkalinization and a vesicular
      acidification. Both, H2O2 (0.2 mmol/l) and t-butyl-hydroperoxide (0.2 mmol/l)
      were without effect on pHcyt, but lowered apparent pHves by about 0.2 pH units.
      Ba2+ (1 mmol/l) diminished the acidifying effect of the hydroperoxides by about
      50%. Pretreatment of the cells with colchicine, but not with lumicolchicine,
      largely abolished the effects of aniso-osmolarity and hydroperoxides on pHves.
      The data suggest that hepatocellular hydration affects the proton gradients built
      up across the membranes of endocytotic FITC-dextran-accessible compartments in a
      microtubule-dependent way. They further suggest that hydroperoxides induce
      vesicular acidification in a colchicine- and Ba(2+)-sensitive way. Because
      hydroperoxides induce Ba(2+)-sensitive cell shrinkage [Hallbrucker, Ritter, Lang,
      Gerok and Haussinger (1992) Eur. J. Biochem. 211, 449-458], the results are
      compatible with the view that hydroperoxide-induced cell shrinkage mediates
      vesicular acidification. It is concluded that modulation of vesicular pH by the
      hepatocellular hydration state may play a role in triggering some metabolic
      changes in response to cell swelling/shrinkage.

PMID- 7524483
TI  - A possible role of tyrosine kinases in the regulation of muscarinic receptor
      activated cation channels in guinea pig ileum.
AB  - We investigated the effects of inhibitors for tyrosine kinases and phosphatases
      on the muscarinic receptor-activated nonselective cationic current. With nystatin
      perforated whole-cell recording, the tyrosine kinase inhibitor genistein (1
      approximately 10 micrograms/ml) reduced the amplitude of currents evoked by
      iontophoretically applied acetylcholine in a dose-dependent manner, the maximum
      inhibition being to about 46% of the control. In contrast, daidzein (10
      micrograms/ml), an inactive analog of genistein, exerted little effect. These
      effects were unchanged when the cationic current was activated by internal
      perfusion of GTP gamma S (50 microM) bypassing the muscarinic receptor. A potent
      phosphatase inhibitor, orthovanadate (30 approximately 100 microM), on the other
      hand, increased the GTP gamma S-induced cationic current. These results suggest
      that tyrosine phosphorylation may be essential to regulate the Ca mobilization
      associated with muscarinic receptor-operated nonselective cation channels.

PMID- 7524482
TI  - Thaliporphine selectively inhibits expression of the inducible, but not the
      constitutive, nitric oxide synthase.
AB  - Formation of nitrites/nitrates caused by lipopolysaccharide (LPS) in J774.2
      macrophages was inhibited by thaliporphine, an aporphine derivative isolated from
      the plant Neolitsea konishii K. This inhibition of nitrite synthesis in LPS
      stimulated macrophages by thaliporphine was similar to that by cycloheximide, NG
      methyl-L-arginine (MeArg) and dexamethasone. Thaliporphine, but not MeArg,
      inhibited expression of inducible NO synthase without directly affecting enzyme
      activity. However, thaliporphine did not inhibit nitrite production by NO
      synthase that had already been induced by prior exposure to LPS for which any
      possible further induction was inhibited by cycloheximide. In endothelial cells,
      nitrite formation induced by bradykinin (in the presence of 0.2 mM Ca2+) was
      inhibited by MeArg. However, incubation of endothelial cells with dexamethasone,
      cycloheximide and thaliporphine did not affect this Ca(2+)-dependent nitrite
      production. Thaliporphine (0.1-100 microM) dose-dependently inhibited nitrite
      accumulation in macrophages stimulated by interleukin-1 beta (IL-1 beta) whereas
      nitrite formation induced by tumour necrosis factor alpha was not inhibited. LPS
      stimulated IL-1 beta synthesis in macrophages was significantly inhibited by
      thaliporphine, but thaliporphine had only minimal effect on LPS-stimulated IL-1
      beta synthesis in endothelial cells. These results demonstrate that thaliporphine
      inhibits LPS induction of NO synthase expression, and that the mechanism of
      action of thaliporphine is via inhibition of LPS-stimulated IL-1 beta synthesis
      in macrophages. In anaesthetized rats subjected to LPS, pretreatment with
      thaliporphine partially restored the fall in mean arterial pressure and the
      vascular hyporeactivity to noradrenaline 3 h after LPS injection. In conclusion,
      thaliporphine selectively inhibited expression of inducible NO synthase, and may
      thus hold potential for the treatment of endotoxaemia.

PMID- 7524484
TI  - Identification of Fas antigen associated with apoptotic cell death in murine
      ovary.
AB  - The majority of ovarian follicles including oocytes undergo atresia through a
      mechanism involving apoptotic cell death. The mechanisms underlying atresia
      remain to be clarified. In the present study, we detected the expression of the
      Fas antigen (Fas), which is a cell-surface protein to modulate apoptosis, in
      murine ovarian oocytes and hyperovulated eggs as well as in several control
      tissues. Substantial decline in Fas mRNA was found in atretic follicles which
      were injected with pregnant mare's serum gonadotropin (PMSG) on day 3. The
      observed decreases in mRNA of Fas could not be attributed to a generalized
      degradation of cellular RNA during atresia, as evidenced by the presence of
      intact 18S and 28S ribosomal RNA as well as constitutive expression of EF-1 alpha
      mRNA in atretic follicles. The data obtained indicate that apoptotic cell death
      of oocytes seemed to be associated with internucleosomal DNA fragmentation
      regulated by Fas molecule expressed in atretic ovarian follicles.

PMID- 7524481
TI  - Agonist-induced internalization of the substance P (NK1) receptor expressed in
      epithelial cells.
AB  - Internalization of the NK1 receptor (NK1R) and substance P was observed in cells
      transfected with cDNA encoding the rat NK1R by using anti-receptor antibodies and
      cyanine 3-labelled substance P (cy3-substance P). After incubation at 4 degrees
      C, NK1R immunoreactivity and cy3-substance P were confined to the plasma
      membrane. Within 3 min of incubation at 37 degrees C, NK1R immunoreactivity and
      cy3-substance P were internalized into small intracellular vesicles located
      beneath the plasma membrane. Fluorescein isothiocyanate-labelled transferrin and
      cy3-substance P were internalized into the same vesicles, identifying them as
      early endosomes. After 60 min at 37 degrees C, NK1R immunoreactivity was detected
      in larger, perinuclear vesicles. Internalization of 125I-labelled substance P was
      studied by using an acid wash to dissociate cell-surface label from that which
      has been internalized. Binding reached equilibrium after incubation for 60 min at
      4 degrees C with no detectable internalization. After 10 min incubation at 37
      degrees C, 83.5 +/- 1.0% of specifically bound counts were internalized.
      Hyperosmolar sucrose and phenylarsine oxide, which are inhibitors of endocytosis,
      prevented internalization of 125I-labelled substance P and accumulation of NK1R
      immunoreactivity into endosomes. Acidotropic agents caused retention of 125I
      labelled substance P within the cell and inhibited degradation of the
      internalized peptide. Continuous incubation of cells with substance P at 37
      degrees C reduced 125I-substance P binding at the cell surface. Therefore,
      substance P and its receptor are internalized into early endosomes within minutes
      of binding, and internalized substance P is degraded. Internalization depletes
      NK1Rs from the cell surface and may down-regulate the response of a cell to
      substance P.

PMID- 7524486
TI  - Dissociation between interleukin-1 beta-induced expression of mRNA for superoxide
      dismutase and nitric oxide synthase in insulin-producing cells.
AB  - We presently investigated the induction of manganese superoxide dismutase (MnSOD)
      and nitric oxide synthase (iNOS) mRNA by interleukin-1 beta (IL-1 beta) in
      insulin-producing RINm5F cells. IL-1 beta induced both mRNAs in parallel, with
      increased levels detectable after 4 h and further increase at 6 h.
      Aminoguanidine, a blocker of NO production, did not prevent IL-1 beta-induced
      MnSOD mRNA expression, and SNP, a NO releasing agent, did not induce MnSOD mRNA.
      Actinomycin D, an inhibitor of gene transcription, prevented IL-1 beta induction
      of both MnSOD and iNOS mRNA. Cycloheximide, an inhibitor of protein synthesis,
      prevented IL-1 beta-induced expression of iNOS mRNA, but not MnSOD mRNA. These
      data suggest that induction of MnSOD mRNA by IL-1 beta is independent of iNOS
      expression and NO production. Moreover, while expression of iNOS mRNA depends on
      protein synthesis, MnSOD mRNA induction does not necessarily require this step.
      Thus, it seems that IL-1 induces genes potentially involved in cell damage (iNOS)
      and defense (MnSOD) by different mechanisms.

PMID- 7524485
TI  - Constitutive mucin secretion linked to CFTR expression.
AB  - Mucus plugging is a hallmark of cystic fibrosis, but the link between the
      defective gene product, the cystic fibrosis transmembrane conductance regulator,
      and the abnormal mucus phenotype is unclear. To demonstrate CFTR involvement in
      mucin glycoprotein secretion in epithelial cells, a retroviral vector was used to
      overexpress CFTR in gallbladder epithelial cells, and constitutive mucin labeling
      and secretion were monitored. Achievement of high-level vector expression was
      confirmed by transduction with marker genes. Cells transduced with vectors
      carrying CFTR cDNA showed 5-fold increased expression of CFTR by Western
      blotting. Mucin labeling and secretion were 4-fold elevated in transduced cells.
      These results suggest constitutive mucin synthesis and secretion in gallbladder
      epithelial cells are regulated by CFTR.

PMID- 7524487
TI  - The aminoterminus of c-Raf-1 binds a 28-kD cellular protein.
AB  - The regulatory aminoterminal domain of c-Raf-1 expressed as glutathione S
      transferase fusion protein associates with a 28-kD cellular protein after
      treatment with lysates from A431 cells. Both proteins become phosphorylated in
      vitro by an unidentified cellular protein kinase also present in the complex. The
      association of the 28-kD protein depends on Cys 168 and Ser 259, suggesting that
      two independent epitopes of c-Raf-1 are required for binding.

PMID- 7524489
TI  - UV radiation induces DNA fragmentation and cell death in B16 melanoma sensitized
      by bromodeoxyuridine: impaired c-jun induction and defective tyrosine
      phosphorylation signalling.
AB  - The relevance of tyrosine phosphorylation and c-jun protooncogene expression to
      radiation sensitization was investigated in B16 melanoma. These cells are
      sensitized by bromodeoxyuridine (BrdU), a thymidine analog, showing extensive DNA
      fragmentation reminiscent of apoptosis, after UV radiation. UV-irradiated
      unsensitized cells did not reveal DNA fragmentation but showed increased
      expression of c-jun and greater protein tyrosine phosphorylation in response to
      sodium vanadate, an inhibitor of tyrosine phosphatases. However, these responses
      were inhibited in UV-irradiated BrdU-treated cells. Our data suggest that the
      bromodeoxyuridine-induced sensitization to radiation can lead to DNA
      fragmentation and cell death, partly because of a defective tyrosine kinase
      signalling and an impaired c-jun expression, both of which appear important for
      cell survival in response to UV radiation.

PMID- 7524490
TI  - Inhibition of the induction of nitric oxide synthase by spermine is modulated by
      aldehyde dehydrogenase.
AB  - The observation that spermine inhibits the endotoxin (lipopolysaccharide; LPS)
      induced production of nitric oxide (NO) in macrophages has been ascribed to the
      conversion of SP to active metabolites by the action of enzymes, such as diamine
      oxidases, found, for example, in bovine sera. Inhibitory effect is also observed
      with the oxidised metabolite of spermine, spermine dialdehyde (SDA). Inhibition
      appears to be at the level of induction of the inducible isoform of NO synthase
      (iNOS). Here we show that the activity of endogenous aldehyde dehydrogenase
      present in the cells influences the degree of inhibition seen with either
      spermine or SDA. Most significantly, inhibition of aldehyde dehydrogenase
      activity greatly increases (100 fold) the ability of spermine to inhibit the
      production of nitrite by LPS- induced macrophages. This is presumably by
      preserving aldehyde metabolites of spermine and thus increasing its action on the
      induction of iNOS. Thus, inhibition of aldehyde dehydrogenase activity in vitro
      or in vivo may be a useful approach to enhance the inhibitory effect of
      polyamines or polyamine aldehydes on iNOS induction.

PMID- 7524488
TI  - Novel endothelial cell activation factor(s) released from activated platelets
      which induce E-selectin expression and tumor cell adhesion to endothelial cells:
      a preliminary note.
AB  - Activation of endothelial cells (ECs) by tumor cells (TCs) to elicit expression
      of adhesion receptors such as selectins and intercellular adhesion molecules
      (ICAMs) has been considered to facilitate TC-EC adhesion, the initial step in TC
      metastasis. Studies reported here indicate that: (i) TC lines tested did not
      activate ECs; (ii) tested TCs activated native (but not inert) platelets, which
      in turn activated ECs to express E-selectin, leading to TC-EC adhesion; (iii)
      auto-aggregation of TCs eventually resulted in adhesion of large TC aggregates to
      ECs; (iv) process ii is inhibited by H7 and calphostin, indicating involvement of
      a signaling process mediated by protein kinases in expression of E-selectin.

PMID- 7524491
TI  - Molecular characterization of HPH-1: a mouse mutant deficient in GTP
      cyclohydrolase I activity.
AB  - GTP cyclohydrolase I catalyzes the initial and rate limiting step of the
      biosynthesis of tetrahydrobiopterin, the cofactor for aromatic amino acid
      hydroxylation. The mouse mutant HPH-1, previously generated by chemical
      mutagenesis, shows a phenylketonuria due to decreased hepatic GTP cyclohydrolase
      I activity. We show that both parameters GTP cyclohydrolase I activity and
      tetrahydrobiopterin synthesis significantly increase after weaning, but remain
      reduced during the lifetime. In the wild type mouse (C57BL/6), interferon-gamma
      and kit ligand induce GTP cyclohydrolase I activity in primed T-cells and in bone
      marrow-derived mast cells, respectively. The same is true for the HPH-1 mutant,
      but the absolute values remain lower throughout. The open reading frame of GTP
      cyclohydrolase I is not affected by the hph-1 mutation as shown by sequencing.
      Northern blot analysis demonstrates a marked decrease in the steady state mRNA
      level specific for GTP cyclohydrolase I.

PMID- 7524492
TI  - A newly cloned phospholipase A2-activating protein elicits Ca2+ oscillations and
      pancreatic amylase secretion via mediation of G protein beta/phospholipase
      A2/arachidonic acid cascades.
AB  - Recently we have demonstrated that in rat pancreatic acini the high affinity
      cholecystokinin receptors are coupled to the phospholipase A2 (PLA2)/arachidonic
      acid (AA) cascades to mediate Ca2+ oscillations and amylase secretion. This
      intracellular signal transduction system is associated with an unidentified G
      protein(s) which is neither Gi/Go nor Gq-alpha. Using a newly cloned PLA2
      activating protein (PLAP), we further examined the mechanisms by which PLA2
      activates Ca2+ oscillation and pancreatic enzyme secretion. In intact acini, 0.1
      1 microM PLAP evoked Ca2+ oscillations in a dose-dependent manner (delta [Ca2+]i:
      18-121 nM and frequency: 2.3-5.5 cycles/10 min). PLAP elicited a 3-fold increase
      in monophasic amylase secretion with an EC50 of 0.1 microM. PLAP dose-dependently
      caused an increase in the AA metabolite 15-HETE. The PLA2 inhibitor, but not
      inhibitors of lipoxygenase, cytochrome P-450 and cyclooxygenase, inhibited the
      action of PLAP, suggesting that AA, but not AA metabolites, functions as a signal
      messenger. In permeabilized acini, a monoclonal antibody of G protein beta
      subunits inhibited the action of PLAP. Because of the structural similarity
      between PLAP and Gbeta protein we hypothesize that the PLA2 coupled G protein is
      Gbeta and it elicits Ca2+ oscillations and monophasic amylase secretion via the
      AA pathway.

PMID- 7524493
TI  - Purification and characterization of a functional soluble fibroblast growth
      factor receptor 1.
AB  - Naturally encoded human soluble fibroblast growth factor receptor 1 was cloned,
      abundantly expressed by recombinant baculovirus-infected insect cells and
      purified to apparent homogeneity. Pure soluble receptor bound as monomeric and
      dimeric complexes and inhibited the mitogenic activity of basic and acidic
      fibroblast growth factors.

PMID- 7524494
TI  - Hepatocyte nuclear factor-3 (HNF-3) binds to the insulin response sequence in the
      IGF binding protein-1 (IGFBP-1) promoter and enhances promoter function.
AB  - IGF binding protein-1 is an important short-term modulator of IGF
      bioavailability. Hepatic transcription of IGFBP-1 is increased by glucocorticoids
      and suppressed by insulin. We previously identified adjacent glucocorticoid and
      insulin response sequences approximately 90 bp 5' to the RNA cap site in the
      IGFBP-1 promoter. This insulin response sequence contains a sequence highly
      related (10/12 bases) to a consensus HNF-3 binding sequence. Gel shift and
      supershift studies confirm that this sequence binds HNF-3 alpha, beta and gamma.
      Co-expression of HNF-3 beta enhances IGFBP-1 promoter activity in NIH-3T3 cells.
      Mutation of this HNF-3 binding sequence disrupts this effect as well as the
      ability of glucocorticoids to stimulate and of insulin to inhibit IGFBP-1
      promoter activity in H4IIE and HepG2 hepatoma cells. HNF-3 binding at this site
      may play an important role in the multihormonal regulation of hepatic IGFBP-1
      gene expression.

PMID- 7524496
TI  - Potent inhibition of insulin receptor dephosphorylation by a hexamer peptide
      containing the phosphotyrosyl mimetic F2Pmp.
AB  - Phosphonomethyl phenylalanine (Pmp) is a non-hydrolyzable phosphotyrosyl (pTyr)
      mimetic, which has been incorporated into eleven-mer Pmp-containing peptides that
      have previously been reported to competitively inhibit the protein-tyrosine
      phosphatases PTP1 and PTP 1B. We have recently shown that phosphonodifluoromethyl
      phenylalanine (F2Pmp) is superior to Pmp as a pTyr mimetic in SH2 domain-binding
      peptides. Herein we find using the hexameric peptide sequence Ac-D-A-D-E-X-L
      amide, where X = (D/L)-Pmp or L-F2Pmp, that the half maximal inhibition values of
      these two peptides against PTP 1B-mediated dephosphorylation of
      autophosphorylated insulin receptor to be 200 microM and 100 nM, respectively.
      These data indicate that F2Pmp induces a three orders of magnitude enhancement in
      affinity relative to Pmp, resulting in an exceptionally potent peptide-based PTP
      inhibitor. We conclude that F2Pmp may be a generally useful tool in the
      preparation of selective, high affinity PTP inhibitors.

PMID- 7524495
TI  - Activation of mitogen-activated protein kinase cascade through erythropoietin
      receptor.
AB  - Erythropoietin is a cytokine which specifically regulates differentiation and
      proliferation of erythroid progenitor cells. We show here that binding of
      erythropoietin to its receptor induced activation of protein tyrosine kinases
      including Jak2, and of Ras, Raf-1, mitogen-activated protein (MAP) kinase kinase
      and MAP kinases (ERK1 and ERK2). Taken together with other observations,
      erythropoietin receptor-mediated signal activates MAP kinase cascade, which is
      the common signaling pathway activated by other cytokines and growth factor
      receptors with tyrosine kinase activity.

PMID- 7524497
TI  - Multiple effector coupling of somatostatin receptor subtype SSTR1.
AB  - The signal transduction pathways of a cloned human somatostatin receptor subtype,
      SSTR1, have been investigated in CHO cells stably expressing this receptor. In
      SSTR1-expressing CHO cells, somatostatin-14 inhibits forskolin-stimulated cAMP
      formation in a dose-dependent manner with an ED50 of 1.0 x 10(-9) M. Somatostatin
      14 also stimulates inositol 1,4,5-trisphosphate formation in a dose-dependent
      manner with an ED50 of 4.0 x 10(-8) M. Somatostatin-14 inhibitory action on
      adenylyl cyclase and stimulatory action on inositol 1,4,5-trisphosphate formation
      are both blocked by pertussis toxin, indicating that these effects of SSTR1 are
      mediated by pertussis toxin-sensitive G protein(s). Antiserum against Gi alpha 3
      blocked the inhibitory effects of somatostatin-14 on forskolin-stimulated
      adenylyl cyclase, but antiserum against Gi alpha 1/Gi alpha 2 did not, indicating
      that Gi alpha 3 dominantly couples SSTR1 to adenylyl cyclase. These results
      demonstrate that SSTR1 can be coupled to different signaling pathways to exert
      multiple biological effects, one of which is mediated by Gi alpha 3.

PMID- 7524498
TI  - Nitric oxide-mediated apoptosis in murine mastocytoma.
AB  - To investigate how the number of mast cells is controlled, we studied a murine
      mastocytoma cell line. Based on electron microscopic observation of nuclear
      condensation and electrophoretic evidence with DNA fragmentation, these
      mastocytoma wells were shown to undergo apoptosis. This apoptosis was dependent
      on the concentrations of serum and L-arginine and was enhanced by TNF-alpha. We
      confirmed that apoptosis was mediated by nitric oxide (NO) synthase; inducible NO
      synthase (iNOS) mRNA was strongly expressed in apoptotic cells, while an
      inhibitor of NOS, NG-monomethyl-L-arginine, and dexamethasone prevented apoptosis
      in addition to inhibiting iNOS mRNA expression. Our results suggest that iNOS
      expression is very important in regulating the proliferation of mast cells under
      pathological conditions.

PMID- 7524499
TI  - Tetrafibricin has a high selectivity for GPIIb/IIIa: comparison of the effects of
      tetrafibricin and RGDS on GPIIb/IIIa and the vitronectin receptor.
AB  - The specificity of tetrafibricin was examined by comparing its activities on
      GPIIb/IIIa and on the vitronectin receptor (alpha v beta 3) with those of Arg-Gly
      Asp-Ser (RGDS) on the same receptors. Tetrafibricin, which inhibited fibrinogen
      GPIIb/IIIa binding 10 times more potently than RGDS, was three orders of
      magnitude less potent compared to RGDS on the inhibition of fibrinogen binding to
      alpha v beta 3. Furthermore, tetrafibricin potently inhibited platelet adhesion
      to both fibrinogen and von Willebrand factor. Whereas, there was no significant
      inhibition observed in the GPIIb/IIIa-independent cellular adhesions. These
      results suggest that tetrafibricin is highly selective for GPIIb/IIIa.

PMID- 7524501
TI  - Lovastatin disrupts early events in insulin signaling: a potential mechanism of
      lovastatin's anti-mitogenic activity.
AB  - The mechanism by which lovastatin lowers cholesterol levels is well characterized
      but little is known about its anti-mitogenic and anti-tumorigenic mechanism. Here
      we demonstrate that lovastatin disrupts early events in the mitogenic signaling
      pathways of insulin. Insulin treatment (200 mM) of quiescent HIR rat-1
      fibroblasts results in an 8-fold stimulation of phosphatidylinositol-3-kinase (PI
      3-K) activity. Overnight pretreatment of cells with lovastatin (20 microM)
      inhibits insulin stimulation of PI-3-K activity by 75%. Immunoprecipitation and
      immunoblotting experiments using antibodies against the regulatory subunit of PI
      3-K (p85), phosphotyrosine, and insulin receptor alpha and beta subunits
      demonstrate that lovastatin inhibits the association of p85 with tyrosine
      phosphorylated insulin receptor substrate-1 and the beta subunit of the insulin
      receptor. Furthermore, lovastatin dramatically reduces (70-100%) the level of
      tyrosine phosphorylated insulin receptor beta subunit following insulin
      stimulation. These results clearly demonstrate that lovastatin disrupts early
      events of insulin mitogenic signaling by reducing the levels of tyrosine
      phosphorylated beta subunit and suggest that this disruption is a potential
      mechanism for the anti-mitogenic effect of lovastatin.

PMID- 7524500
TI  - Cyclosporin A blocks induction of tumor necrosis factor-alpha in human B
      lymphocytes.
AB  - The effects of cyclosporin A (CSP) on tumor necrosis factor-alpha (TNF-alpha) RNA
      levels and protein production in human B cells and a B cell line were studied.
      The ability of CSP to block induction of RNA was compared to its inhibition of
      protein production in response to anti-IgM, phorbol ester (PMA) and platelet
      activating factor (PAF). PAF is a phospholipid which has recently been found to
      activate human B cells. CSP blocks PAF-induced TNF-alpha RNA from the Ramos cell
      line, as well as inhibiting the enhancement of TNF protein production from both
      freshly isolated and Ramos B cells. CSP also blocks anti-Ig induced TNF-alpha RNA
      and protein but does not inhibit PMA-induced TNF-alpha. We conclude that B cells,
      like T cells, have CSP-independent and CSP-dependent signaling pathways and that
      PAF signaling is dependent upon a CSP-sensitive factor.

PMID- 7524503
TI  - Characterization of monoclonal antibodies to chitinase A1 and enhancement of
      chitinase A1 activity by monoclonal antibodies.
AB  - A total of eleven hybridomas which secrete antibodies against chitinase A1 were
      established. Among the eleven monoclonal antibodies (MAbs) obtained, six
      recognized the catalytic domain, three recognized the type III region and two
      recognized the chitin binding domain of chitinase A1. Of the two MAbs which
      recognized the chitin binding domain one was found to also react with chitinase
      D, but none of the other MAbs which recognized either the type III region or the
      chitin binding domain reacted with chitinase D despite the extensive amino acid
      sequence similarity between both the type III and chitin binding domains of the
      two chitinases. Two of the eleven MAbs enhanced chitinase activity significantly,
      while the other MAbs did not have any significant effect on chitinase A1
      activity.

PMID- 7524502
TI  - Evidence for a globin promoter-specific silencer element located upstream of the
      human delta-globin gene.
AB  - We describe the negative regulatory activity of a 1.7 kilobase (kb) region (R) in
      the human beta-globin locus located between 4.0 and 2.3 kb upstream of the delta
      globin gene capsite, using a transient assay with the chloramphenicol
      acetyltransferase (CAT) reporter gene in mouse erythroleukemia (MEL) cells. The R
      region is deleted in most cases of deletion hereditary persistence of fetal
      hemoglobin (HPFH), but is unaffected in most delta beta zero-thalassemias.
      However, no experiments addressing its function in globin gene expression have
      been reported to date. We show that R inhibits CAT expression of constructs
      containing a fetal (gamma) or adult (beta) globin gene promoter, but does not
      affect expression of similar constructs using a non-globin (SV40) promoter. The
      inhibitory effect on the beta-globin promoter can be localized to a 651 bp sub
      region of R. For the gamma-globin promoter, no sub-region of R can reproduce the
      level of inhibition associated with the entire region.

PMID- 7524504
TI  - Inhibition by FK506 of formyl peptide-induced neutrophil activation and
      associated protein synthesis.
AB  - The macrolide FK506 inhibited, by up to 50%, neutrophil migration and the
      production of the superoxide radical in response to the formyl peptide, formyl
      methionyl-leucyl-phenylalanine (FMLP). The production of the superoxide radical
      in response to phorbol 12-myristate 13-acetate (PMA) was unaffected by FK506. The
      inhibition of neutrophil functions was accompanied by a partial reversal of FMLP
      induced synthesis of cellular proteins, despite a rise in intracellular Ca2+.
      Neutrophils treated with FK506 demonstrated a small (average 23%) though
      significant decrease in formyl-peptide receptor numbers but receptor binding
      affinity was unaffected. The effects of FK506 on neutrophil activation appear to
      be analogous to those in T-lymphocytes. The incomplete inhibition, by FK506, of
      neutrophil responses suggests further that activation by FMLP is mediated via
      distinct multiple signalling pathways, including protein kinase activation and
      protein synthesis. The inability of FK506 to reduce FMLP-induced rises in
      cellular Ca2+ or PMA-induced activation of neutrophils suggests that its action
      is distal to Ca2+ mobilization and distinct from pathways relying on PKC
      activation. Thus the immunosuppressive effects of FK506 in vivo might be mediated
      through the inhibition of inflammatory cells other than lymphocytes and the drug
      therefore has therapeutic potential in a variety of inflammatory conditions. The
      drug also has potential in vitro for the characterization of signalling pathways
      from the plasma membrane to the nucleus.

PMID- 7524505
TI  - Absorption enhancement of hydrophilic compounds by verapamil in Caco-2 cell
      monolayers.
AB  - Caco-2 monolayers were used to determine whether verapamil enhanced the transport
      of hydrophilic compounds across epithelial cells. Transepithelial electrical
      resistance (TEER) measurements, as an indicator of the opening of tight
      junctions, and transport experiments with fluorescein-Na (Flu) and FITC-dextran
      Mw 4000 (FD-4) were used to assess the effect. (+/-) Verapamil concentrations up
      to 3 x 10(-4) M increased TEER dose-dependently, whereas from concentrations of 7
      x 10(-4) M onwards a dose-dependent drop was found. After removal of verapamil (<
      10(-3) M) the effects on TEER were reversible within 30 min. A second
      administration of verapamil after different time intervals produced a much larger
      effect on TEER than the first administration. The separate R- and S-enantiomers
      did not reveal a difference in enantiomer effect. (+/-) Verapamil at 7 x 10(-4) M
      increased Flu transport about 13-fold and 26-fold after the first and second
      treatment in the same monolayers, respectively. Transport of FD-4 increased
      approximately 4-fold and 6-fold after the first and second treatment,
      respectively. Potential damaging effects were assessed by trypan blue exclusion
      (cell death) and cell detachment. No cell death occurred at verapamil
      concentrations of 8.5 x 10(-4) M or lower, whereas cell detachment did not occur
      within 1 hr at all concentrations used in these experiments. At later times
      detachment was observed at concentrations of 7 x 10(-4) M and higher. Confocal
      laser scanning microscopy showed that verapamil opens the paracellular route,
      thereby enhancing the permeability of hydrophilic compounds. However, relatively
      high concentrations are needed to achieve this effect and only a narrow
      concentration range can be used without cytotoxic effects, which limits the
      potential application of verapamil as an absorption enhancing agent.

PMID- 7524506
TI  - The selenium analog of methimazole. Measurement of its inhibitory effect on type
      I 5'-deiodinase and of its antithyroid activity.
AB  - Methimazole (MMI), unlike propylthiouracil (PTU) is a poor inhibitor of type I
      iodothyronine deiodinase (ID-1). Inhibition of the enzyme by PTU was attributed
      initially to formation of a mixed disulfide between PTU and a cysteine residue at
      the active site. Presumably, MMI was unable to form a stable mixed disulfide and
      thus did not inhibit the enzyme. However, it has been demonstrated recently that
      ID-1 is a selenium-containing enzyme, with selenocysteine, rather than cysteine,
      at the active site. This observation raised the possibility that the selenium
      analog of MMI, methyl selenoimidazole (MSeI), might be a better inhibitor of ID-1
      than MMI itself, as formation of the Se-Se bond with the enzyme would be expected
      to occur more readily than formation of the S-SE bond. To test this possibility,
      we developed a procedure for the synthesis of MSeI and compared MSeI with MMI and
      PTU for inhibition of ID-1 and for antithyroid activity. For inhibition of ID-1,
      MMI and MSeI were tested at concentrations of 10-300 microM. No significant
      inhibition was observed with MMI. MSeI showed slight but significant inhibition
      only in the 100-300 microM range. PTU, on the other hand, showed marked
      inhibition at 1 microM. Thus, replacement of the sulfur in MMI with selenium only
      marginally increases its inhibitory effect on ID-1. As an inhibitor of ID-1, MSeI
      is much less than 1% as potent as PTU. MMI and MSeI were also compared for
      antithyroid activity, both in vivo and in vitro. As an inhibitor of the catalytic
      activity of thyroid peroxidase, MMI was 4-5 times more potent than MSeI in a
      guaiacol assay, but only twice as potent in an iodination assay. In in vivo
      experiments with rats, MMI was at least 50 times more potent than MSeI in
      inhibiting thyroidal organic iodine formation. The relatively low potency of MSeI
      in vivo suggests that it is much less well concentrated by the thyroid than in
      MMI.

PMID- 7524508
TI  - Long-term iloprost infusion therapy for severe pulmonary hypertension in patients
      with connective tissue diseases.
AB  - OBJECTIVE: To determine the effects of short-term, maximum-tolerated-dose and
      long-term, optimum-dose iloprost treatment of severe pulmonary hypertension
      associated with systemic sclerosis (SSc) and the primary antiphospholipid
      syndrome (APS). METHODS: Three patients with SSc and 2 with APS who had failed to
      respond to oral vasodilator therapy for pulmonary hypertension were enrolled in a
      32-week, open, prospective trial. Short-term infusion of maximum-tolerated doses
      and continuous infusion of optimum doses of iloprost were carried out following
      baseline cardiac catheterization. Catheterization was repeated at 2 and 32 weeks.
      All 5 patients completed the study and continued therapy for an average of 82
      weeks (range 58-103). RESULTS: Acute infusion of maximum tolerated doses
      significantly ameliorated the cardiac index (0.92 liters/minute/m2; P < 0.01),
      pulmonary artery O2 saturation (10.6%; P < 0.05), and pulmonary resistance (-6.7
      units; P < 0.05). After 2 weeks of continuous infusion of optimum doses, there
      was improvement in pulmonary resistance (> or = 16%) and pulmonary artery O2
      saturation (> 30%) in the 2 patients with primary APS. After 2 and 32 weeks, the
      3 SSc patients showed variable hemodynamic responses. New York Heart Association
      functional class and exercise tolerance improved in all patients. There was 1
      episode of bacteremia, and 1 patient died after 72 weeks of study. CONCLUSION:
      Continuous iloprost infusion may improve exercise tolerance and quality of life
      in patients with severe pulmonary hypertension associated with SSc and primary
      APS.

PMID- 7524507
TI  - Autoimmune disease. A problem of defective apoptosis.
AB  - Human autoimmune diseases share the common feature of an imbalance between the
      production and destruction of various cell types including lymphocytes (SLE),
      synovial cells (RA), and fibroblasts (scleroderma). Patients with SLE have
      increased levels of soluble Fas that inhibit proper apoptosis of lymphocytes. In
      animal models of autoimmune diseases, mutations of genes involved in apoptosis
      including Fas, Fas ligand, and the hematopoietic cell phosphatase gene have been
      identified. Oncogenes, including bcl-2, p53, and myc, that regulate apoptosis are
      also expressed abnormally. Potent inducers of apoptosis including steroids,
      azathioprine, cyclophosphamide, and methotrexate are the most efficacious
      therapies for autoimmune disease currently known. Specific therapies that induce
      apoptosis without incurring side effects should improve treatment of autoimmune
      disease.

PMID- 7524509
TI  - Indication for and caution in the use of granulocyte colony-stimulating factor
      for the treatment of Felty's syndrome: comment on the report by Yasuda et al.

PMID- 7524511
TI  - Individuals with Disabilities Education Act (PL 101-476).

PMID- 7524510
TI  - Lymphocyte function-associated antigen 1 overexpression and T cell
      autoreactivity.
AB  - OBJECTIVE: To determine if DNA methylation inhibitors make T cells autoreactive
      by inducing lymphocyte function-associated antigen type 1 (LFA-1) (CD11a/CD18)
      overexpression. METHODS: T cell clones were treated with 3 distinct DNA
      methylation inhibitors or were stably transfected with a CD18 cDNA in a mammalian
      expression vector, and the effects on LFA-1 expression and activation
      requirements were examined. RESULTS: LFA-1 overexpression, caused by DNA
      methylation inhibitors or by transfection, correlates with the development of
      autoreactivity. CONCLUSION: LFA-1 overexpression may contribute to T cell
      autoreactivity.

PMID- 7524512
TI  - Alpha-fetoprotein in women during pregnancy and in the neonate during
      intrapartum.
AB  - To evaluate alpha-fetoprotein (AFP) levels in women during pregnancy and in the
      neonate, 256 singleton pregnancies without medical, gynecologic, obstetric, or
      neonatal complications were studied. Sera for measuring maternal AFP (MAFP)
      levels were taken in midtrimester (16 to 18 weeks), third trimester (32 to 34
      weeks), and during intrapartum (38 to 41 weeks). For measuring umbilical arterial
      AFP (UAAFP) and umbilical venous AFP (UVAFP) levels, sera of newborn were taken
      from the umbilical cord at delivery. AFP levels were measured by
      radioimmunoassay. Our results show that the MAFP levels at third trimester were
      higher than during intrapartum or midtrimester. Birthweights correlated well with
      MAFP levels in midtrimester. However, they did not significantly correlate with
      the MAFP levels at third trimester or intrapartum, nor with UAAFP or UVAFP
      levels. UAAFP levels were not significantly different from UVAFP levels.
      Intrapartum MAFP correlated well with UAAFP but not with UVAFP, birthweight, or
      parity. The concentration gradient between fetal and maternal serum during
      intrapartum is approximately 750:1. We conclude that MAFP levels in midtrimester
      can reflect birthweight. The data of normal AFP gradient may also be useful for
      diagnosing intrapartum fetomaternal hemorrhage.

PMID- 7524513
TI  - Role of elevated alpha-fetoprotein in prenatal diagnosis of junctional
      epidermolysis bullosa and pyloric atresia.
AB  - A case of junctional epidermolysis bullosa, Herlitz variant, and pyloric atresia
      in a 33 weeks' gestation male infant is reported. The second trimester amniotic
      fluid exhibited elevated concentrations of alpha-fetoprotein and presence of
      acetylcholinesterase; however, the fetus appeared anatomically normal by multiple
      high-resolution ultrasound examinations. This case, as well as others previously
      reported, shows that serious fetal skin disease should be considered as part of
      the differential diagnosis whenever persistent elevation of alpha-fetoprotein and
      presence of acetylcholinesterase are found in the amniotic fluid of a fetus that
      appears anatomically normal by ultrasound. Prenatal diagnosis may be established
      by fetal skin biopsy and extensive prenatal counseling should be offered to
      families on the basis of the prognosis and severity of this disease.

PMID- 7524515
TI  - Hyphodontal, a new antifungal inhibitor of reverse transcriptases from
      Hyphodontia sp. (Corticiaceae, Basidiomycetes).
AB  - In a search for inhibitors of RNA-directed DNA polymerases a new isolactarane
      sesquiterpenoid, hyphodontal (1), was isolated from fermentations of a Canadian
      Hyphodontia species. Its structure was elucidated by spectroscopic methods.
      Hyphodontal strongly inhibits the growth of several yeasts and is a non
      competitive inhibitor of avian myeloblastosis virus (Ki 346 microM) and Moloney
      murine leukemia virus (Ki 112 microM) reverse transcriptases. In addition,
      cytotoxic and antifungal activities were observed.

PMID- 7524516
TI  - Sources of variation in the assessment of cell proliferation using proliferating
      cell nuclear antigen immunohistochemistry.
AB  - The reproducibility in quantitation of proliferation activity, determined using
      the monoclonal antibody 19A2 to proliferating cell nuclear antigen (PCNA), was
      tested in visual and computer-assisted analyses of brain tumor material. The PCNA
      labeling index was scored using count (PCNA-LI, visual and computer analyses) and
      area (PCNA-LIa, computer analysis) estimates of immunopositivity. The quality of
      immunostaining was the most important reason for variation in the assessment
      results. Other significant variation sources in the assessment were experience in
      selecting microscopic fields and distinguishing immunopositive nuclei from
      immunonegative ones. Computer-assisted analysis improved the reproducibility of
      quantitation between different observers (visual rPCNA-LI = 0.624 versus computer
      assisted rPCNA-LI = 0.904). Also, the use of PCNA-LIa improved the intraobserver
      and interobserver reproducibility in different stainings (observer 1:rPCNA-LI =
      0.857 versus rPCNA-LIa = 0.874; observers 1 and 2: rPCNA-LI = 0.904 versus rPCNA
      LIa = 0.927; observers 3 and 4: rPCNA-LI = 0.848 versus rPCNA-LIa = 0.906). PCNA
      LIa by computerized image analysis improves accuracy in the evaluation of the
      granularly expressed PCNA level. Furthermore, the effect of tumor heterogeneity
      on the assessment results can be diminished with the computerized method because
      large tissue areas can be analyzed faster.

PMID- 7524514
TI  - Zn2Mg alkaline phosphatase in an early ptolemeic mummy.
AB  - Bone samples of a ptolemeic mummy have been employed to study the mode of
      conservation on the intactness of Zn2Mg alkaline phosphatase in both structure
      and catalytic activity. A protein of M(r) = 190 +/- 10 kDa being identical to the
      200 kDa enzyme of fresh human bones was successfully isolated. Regardless of age
      200 kDa protein bands and a distinct subunit at 60 kDa were seen in SDS-PAGE
      electrophoresis. The 200 kDa band was also monitored by activity staining. The
      specific activity was 120 mU/mg and 65% of the respective activity obtained in
      the identical preparation using fresh human tibia or rib. The enzymic activity
      was inhibited in the presence of 1,10-phenanthroline and L-homoarginine.
      Radiocarbon dating supported the assignment of the mummy to the early ptolemeic
      period. Among the many bactericidal and fungicidal components employed for
      mummification were aromatic alcohols, mono- and sesquiterpenes. Pistachio resin
      was the major balm resin used. The microbiological sterility of the bone surface
      was ascertained by independent bacterial and fungal examinations.

PMID- 7524517
TI  - Morphonuclear comparison of the mantle zone and diffuse subtypes of mantle cell
      lymphoma.
AB  - Mantle cell lymphoma (MCL) is a distinct type of non-Hodgkin's lymphoma, which,
      based on the architectural pattern, has been divided into mantle zone (MCL-MZ),
      allegedly associated with longer survival, and diffuse (MCL-D) subtypes. To
      determine whether there are morphonuclear differences between MCL-MZ and MCL-D,
      37 fine needle aspirates (FNAs) obtained from 32 patients with MCL (21 cases of
      MCL-MZ and 11 of MCL-D) were evaluated using digital cell image analysis. Twenty
      one morphometric parameters related to geometry, color, texture and densitometry
      were evaluated on 100 cells from each case. Aspirated material was stained with
      either the Diff-Quik or Feulgen method. Statistical analysis (student's t test
      and nonparametric Mann-Whitney test) was performed. No significant differences
      between MCL-MZ and MCL-D were found in any of the 21 studied morphonuclear
      parameters. The morphometric analysis results were similar using the Diff-Quik
      and Feulgen techniques. This study confirmed the overlapping cytologic spectrum
      of MCL-MZ and MCL-D and indicated that histologic specimens demonstrating a
      specific architectural pattern are necessary to differentiate these two variants
      of MCL. Either Diff-Quik- or Feulgen-stained tissues may be used for
      morphonuclear measurements in FNAs of MCL since both give similar results.

PMID- 7524518
TI  - The role of CD40 in the regulation of humoral and cell-mediated immunity.
AB  - The dynamic and reciprocal communication between T helper (Th) cells and B cells
      appears to rely on the provision of multiple signals. The first is antigen
      specific and is mediated by the interaction between the T-cell receptor (TCR) and
      antigen bound to the major histocompatibility complex (MHC). The subsequent
      signals are provided by the binding of accessory molecules such as CD28 and CD40
      to their respective ligands. Here, Fiona Durie and colleagues discuss the co
      stimulatory role of the interaction between CD40 on B cells and CD40 ligand
      (CD40L, gp39) on T cells, and review evidence that suggests blocking this
      interaction may induce T-cell tolerance.

PMID- 7524519
TI  - MHC class II signaling in B-cell activation.
AB  - The cognate interaction between T cells and antigen-presenting cells (APCs),
      mediated by major histocompatibility complex (MHC) class II molecules, results in
      the delivery of activation signals to the APC. These signals contribute to the
      expression of co-stimulatory activity by APCs and have important consequences for
      cell effector function. MHC class II molecules also serve as receptors for B-cell
      stimulation by microbial superantigens. In this review, Paul Scholl and Raif Geha
      discuss recent advances in our understanding of mechanisms of MHC class II
      signaling and analyse their role in human B-cell activation.

PMID- 7524520
TI  - Molecular mechanisms regulating CD19, CD20 and CD22 gene expression.
AB  - The CD19, CD20 and CD22 genes encode transmembrane proteins that are of vital
      importance to B-cell function. Similar to the immunoglobulin (Ig) genes, they are
      expressed in a lineage-specific and developmentally regulated manner. Here, John
      Kehrl and colleagues describe how an understanding of the transcriptional
      regulation of the CD19, CD20 and CD22 genes is leading to valuable insights into
      some of the important molecular events that occur in B-cell development and
      differentiation.

PMID- 7524521
TI  - The CD19/CD21 signal transduction complex of B lymphocytes.
AB  - CD19 and CD21 are B-cell surface molecules that associate with each other and
      with CD81 and Leu-13 to generate a signal transduction complex that is
      independent of the antigen receptor. Current studies, reviewed here by Thomas
      Tedder, Liang-Ji Zhou and Pablo Engel, indicate an important biological role for
      this protein complex in the regulation of B-cell development and activation.

PMID- 7524523
TI  - [Analysis of membrane expression of the CD63 human basophil activation marker.
      Applications to allergologic diagnosis].
AB  - On the basis of the CD 63 bi-modal expression on the membrane of activated
      basophils, we set up a flow cytometric method for the analysis of human basophils
      activation by an anti-IgE and anti-CD 63 double labelling. We demonstrated that
      the statistical characteristics of the percentages of activation obtained by an
      anti-IgE stimulation allowed the use of this method for pharmacological studies.
      The percentages of activation were of the same order of magnitude than those
      obtained by histamine release. CD 63 expression was also observed for a low
      affinity allergen such as the sulfonyl-HSA conjugate used for sulfites
      hypersensibility diagnosis, healthy donors being negative. This method, which can
      be automatized may represent an interesting candidate in the field of hapten
      hypersensitivity which lacks of reliable diagnostical methods.

PMID- 7524524
TI  - [Anecdotes of allergology].

PMID- 7524526
TI  - Appearance of the myofibroblastic phenotype in Dupuytren's disease is associated
      with a fibronectin, laminin, collagen type IV and tenascin extracellular matrix.
AB  - The proliferative nodules of Dupuytren's disease are electron microscopically
      characterized by the occurrence of myofibroblasts with a basal lamina-like
      material. As reported in the literature, immunohistochemical investigations
      showed a fibronectin matrix but failed to demonstrate laminin. This discrepancy
      between electron microscopic features and immunohistochemical findings prompted
      us to examine the composition of extracellular matrix (fibronectin, laminin,
      collagen type IV and tenascin) in relation to the myofibroblast phenotype in
      proliferative nodules from 13 native surgical specimens of nodular palmar
      fibromatosis (Dupuytren's disease). The immunohistochemical staining for
      fibronectin was positive within the whole palmar aponeurosis and was particularly
      intense in the proliferative areas, whereas laminin, collagen type IV and
      tenascin labelling was restricted to the alpha-smooth muscle actin-positive
      proliferative nodules. To exclude definitively an unspecific laminin labelling,
      SDS-PAGE and immunoblot were performed. The electrophoretic pattern of
      Dupuytren's disease tissue revealed laminin and was in congruence with human
      placental tissue used as positive control. The results substantiate an
      extracellular matrix formation by myofibroblasts with fibronectin, laminin,
      collagen type IV and tenascin as constituents. Therefore, laminin expression can
      no longer be considered to be a distinguishing feature between myofibroblasts and
      smooth muscle cells.

PMID- 7524525
TI  - Severity of abnormality influences decision to terminate pregnancies affected
      with fetal neural tube defects.
AB  - We examined parental decision concerning pregnancy management in women having
      fetuses with neural tube defects (NTDs) to determine whether severity of defect
      or method of detection has an impact on the decision making process. Analysis of
      decisions by 50 women, whose pregnancies were affected by an isolated neural tube
      defect (NTD) and characterized by a singleton gestation at 24 gestational weeks
      or less with normal chromosomal complement (46,XX or 46,XY), were assessed. All
      23 women carrying fetuses with anencephaly elected to terminate their
      pregnancies. Of the 27 women carrying fetuses with spina bifida, 21 (77.8%)
      elected to terminate their pregnancies and 6 (22.2%) elected to continue their
      pregnancies. Of the 6 pregnancies that were continued, 4 were initially detected
      by ultrasonography and 2 were ascertained by maternal serum alpha-fetoprotein
      screening; defects ranged from 2 to 14 vertebral bodies, and none of the defects
      were craniad to the T9 level. This is in comparison to 5 of the 21 spina bifida
      cases that were elective pregnancy terminations, which were characterized by
      fetal lesions craniad to the T9 level. Severity of NTD thus appears to influence
      the decision to continue or terminate an affected pregnancy.

PMID- 7524522
TI  - CD20: a regulator of cell-cycle progression of B lymphocytes.
AB  - CD20 is a B-cell-specific cell-surface molecule with four membrane-spanning
      domains, as well as cytoplasmic N- and C-terminal domains. Here, Thomas Tedder
      and Pablo Engel discuss the suggestion that CD20 is a regulator of transmembrane
      Ca2+ conductance and plays an important functional role in B-cell activation,
      proliferation and differentiation.

PMID- 7524527
TI  - Increased adhesion and activation of polymorphonuclear neutrophil granulocytes to
      endothelial cells under heavy metal exposure in vitro.
AB  - Heavy metals have been implicated in the mechanisms of endothelial damage.
      Influences of heavy metal ions on diverse cell types have been studied using a
      variety of in vitro and in vivo methods. Polymorphonuclear neutrophil
      granulocytes (PMNs) have physiological and pathological functions, including the
      modulation of adhesion to and destruction of endothelial cells (ECs). PMNs were
      studied during interaction with human umbilical vein ECs under exposure to zinc,
      nickel and cobalt using an in vitro model. We studied adhesion processes with the
      help of a computer-controlled image-analyzing system and examined the activation
      of PMNs by quantification of leukotriene B4 (LTB4) release. The biphasic effects
      of the evaluated heavy metals on PMN-EC adhesion, with stimulation at very high
      and very low molar concentrations, were observed. The release of LTB4 by PMNs
      increased during exposure to very low metal concentrations. The initiation of
      these important pathogenetic mechanisms of inflammation at very low metal ion
      concentrations, which give no morphological changes, must be regarded as
      potentially significant with respect to the toxic effects of heavy metals.

PMID- 7524528
TI  - 'Lupus-prone' mice are susceptible to organ-specific autoimmune disease,
      experimental allergic encephalomyelitis.
AB  - Immunization with the multideterminant autoantigen myelin basic protein (MBP)
      causes experimental allergic encephalomyelitis (EAE), a T-cell-mediated
      autoimmune disease that serves as a model for multiple sclerosis (MS). MBP
      peptides Ac1-11 and p35-47 induce potent EAE in mice of the H-2u haplotype. T
      cells specific for Ac1-11 predominantly utilize one T-cell receptor (TCR) V beta
      gene segment, V beta 8.2. All T-cell clones and hybridomas analyzed, regardless
      of TCR V beta usage, utilize D beta 2 and J beta 2 elements. The NZW mouse strain
      (H-2z), which contributes to the spontaneous 'lupus-like' illness in (NZB x
      NZW)F1 mice, has a genomic deletion encompassing D beta 2 and J beta 2 gene
      segments. The NZW strain expresses class II (I-A and I-E) genes which share
      identical sequences with H-2u class II. We investigated whether these strains are
      susceptible to EAE induced with intact MBP and known encephalitogenic MBP
      peptides. In vitro analysis demonstrated that NZW antigen-presenting cells (APC)
      can present MBP and MBP peptide Ac1-11 to an encephalitogenic T-cell clone
      derived from an H-2u mouse, confirming the functional identity of NZW class-II (I
      A) molecules with their respective H-2u class-II gene products. In vivo results
      demonstrated that NZW and (NZB x NZW)F1 mice are susceptible to EAE induced with
      intact MBP and Ac1-11. MBP p35-47 caused EAE in (NZB x NZW)F1 mice, which express
      alleles for both the normal (NZB) TCR beta-gene locus, and the abnormal (NZW) TCR
      beta-gene locus containing the J beta 2 deletion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7524530
TI  - Could the cytokeratin molecule be modulated during tumor transformation in
      hepatocellular carcinoma?
AB  - The stability of cytokeratin during tumor transformation in hepatocellular
      carcinoma was studied. We applied biochemical methodology to look into the
      switching of cytokeratin molecules in tumor transformation. First, by
      centrifugation the cytokeratin molecules were extracted from both liver and
      hepatoma tissues. The extracts were then soaked with cyanogen bromide-activated
      Sepharose 4B beads previously coated by monoclonal anti-cytokeratin antibody. The
      bound molecules were then released from the resin with salt. Second, the isolated
      molecules of both were treated with lysosomal enzyme and analyzed on two
      dimensional gels. The results demonstrated that there was a modulation in
      cytokeratin molecules, and the hepatoma cytokeratin was generated from the
      hepatocyte cytokeratin.

PMID- 7524529
TI  - Alterations in expression of terminal differentiation markers of keratinocytes
      during oral carcinogenesis.
AB  - Expression of cytoskeletal proteins has been shown to be dependent on the
      differentiation status of the tissue. In the present study, expression of two
      cytoskeletal proteins normally present in terminally differentiated
      keratinocytes, namely cytokeratin types 10/11 and involucrin, were studied in
      different stages of tumour progression in the oral mucosa. Results showed that
      cytokeratins 10/11 and involucrin strongly correlated with the differentiation
      status of cells. High expression was observed in non-dysplastic hyperplastic
      epithelium as compared to normal, dysplastic and neoplastic epithelium. In
      addition, various grades of dysplasia showed an inverse correlation with
      expression of these proteins. Statistical analysis of the results also showed a
      negative correlation between the differentiation of upper spinal cells and the
      stage of tumour progression. It therefore appears that the proteins studied may
      be useful as markers for epithelial carcinogenesis.

PMID- 7524531
TI  - Cyclosporin A, FK506, and rapamycin: binding to immunophilins and biological
      action.

PMID- 7524532
TI  - Contribution of the vagus nerve in mediating the memory-facilitating effects of
      substance P.
AB  - The present study determined whether the effects of peripherally administered
      substance P on memory are mediated via activation of the vagus nerve. Rats were
      submitted to subdiaphragmatic vagotomy, sham vagotomy or non-operated, and
      trained in a step-down inhibitory avoidance task and tested 24 h later.
      Posttraining administration of 50 micrograms/kg of SP facilitated retention
      performance in non-operated and sham-operated groups. The facilitating effects of
      50 micrograms/kg of SP was blocked by vagotomy, although vagotomy did not
      attenuate the memory-enhancing effects of larger doses (250 and 500
      micrograms/kg). These results suggest that the mnemotropic effects of
      peripherally administered SP are sensitive to the functional integrity of the
      vagus nerve. Alternatively, the vagus nerve may be one pathway but not the only
      pathway by which systemic SP influences the memory storage processes in the
      brain.

PMID- 7524534
TI  - Substance P is involved in the sensitization of the acoustic startle response by
      footshocks in rats.
AB  - The acoustic startle response (ASR) can be enhanced by administration of
      footshocks (sensitization). The neural mechanisms underlying this effect are
      largely unknown. A previous electrophysiological study (Kungel et al., Brain
      Res., 643 (1994) 29-39) has shown that the neuropeptide substance P (SP)
      increases the responsiveness to acoustic stimuli of neurons in the caudal pontine
      reticular nucleus (PnC). Since the PnC is an important part of the primary
      acoustic startle circuit, we hypothesized that SP is involved in the enhancement
      of the ASR by electric footshocks. We tested this hypothesis in different
      experiments by locally injecting SP and SP-antagonists into the PnC of freely
      moving rats. The present data show that SP (0.5 pmol-1 nmol) locally injected
      into the PnC dose-dependently increases the amplitude of the ASR in rats. This
      effect was antagonized by pretreatment with the SP-antagonist CP-96,345.
      Furthermore, we show that the sensitization of the ASR by 0.6 mA-footshocks can
      be blocked by local microinjections of the SP-antagonists CP-96,345 (5 pmol-10
      nmol) or CP-99,994 (0.5 nmol-100 nmol) into the PnC. Possible pathways relevant
      for the sensitization of the ASR are discussed.

PMID- 7524533
TI  - The effects of dorsal and ventral noradrenergic system lesions with DSP-4 on
      emotional-defensive behavior and regional brain monoamines content in the cat.
AB  - As a result of selective lesions of dorsal (DB) and ventral (VB) noradrenergic
      system (DSP-4 i.c.) it was observed that these two systems are functionally
      differentiated and only DB participates in the regulation of post-carbachol
      emotional-defensive behavior in the cat. Following DB lesion an increase in
      emotional-defensive excitation occurred and HPLC analysis showed a significant
      reduction of NA concentration in the posterior hypothalamus, midbrain central
      gray matter and frontal cortex and decreased turnover of 5-HT in all "emotional
      brain areas" (hypothalamus, midbrain, amygdala, hippocampus) and frontal cortex.
      Following VB lesion there were no significant changes of post-carbachol defensive
      behavior and HPLC analysis showed a significant reduction of NA in the anterior
      and posterior hypothalamus, midbrain central gray matter and amygdala and an
      increased turnover of 5-HT in the posterior hypothalamus and midbrain central
      gray matter. The results obtained can be interpreted in relation to functional
      interactions between the NA and 5-HT systems.

PMID- 7524535
TI  - Pentapeptide identified as a monoclonal antibody binding site in the serine
      protease domain of t-PA.
AB  - The first defined sequential epitope of the tissue plasminogen activator (t-PA)
      was determined by a monoclonal antibody against a synthetic peptide segment
      corresponding to peptide sequence 341-354 of t-PA. This segment was selected by
      computer assisted epitope prediction. Balb/c mice were immunized with catalase
      peptide and tripalmitoyl-S-glyceryl-cys-teinyl-seryl-peptide conjugates. A
      monoclonal antibody derived from this immunization was reactive with native
      recombinant t-PA (rt-PA) and reduced carboxymethylated recombinant t-PA (RCM rt
      PA). The sequential epitope was detected by Pepscan method using overlapping octa
      and nonapeptides. By fine epitope mapping with tetra-, penta-, hexa- and
      heptapeptides the epitope was minimized to the pentapeptide EEEQK (347-351).
      Replacement set analysis confirmed the importance of this amino acid sequence,
      especially of the amino acid E348, for antibody binding. Functional assays of rt
      PA were not affected by this antibody indicating that the epitope has no
      influence on the enzymatic center and the binding site of the inhibitor. The
      analysis demonstrates that the predicted recognition site of the monoclonal
      antibody 17-134/11 is exposed on the surface of the native rt-PA molecule.

PMID- 7524537
TI  - Immunodeficiency due to a faulty interaction between T cells and B cells.
AB  - The identification of the ligand for CD40, gp39, which is expressed on the
      membrane of activated CD4+ T-helper cells, has sparked intense investigation into
      the roles of this molecule in physiological B-cell activation. Recently, it has
      become clear that some human immunodeficiencies, such as X-linked hyper IgM
      syndrome and common variable immunodeficiency are linked to mutations in the gp39
      gene or are a result of defective expression of gp39, leading to suboptimal, or a
      lack of, B-cell activation by T-helper cells.

PMID- 7524538
TI  - Modulation of DNA supercoiling by interaction with netropsin and other minor
      groove binders.
AB  - The assay of DNA unwinding by ethidium, followed by sedimentation velocity
      techniques, was applied to complexes of supercoiled plasmid DNA with different
      non-intercalating drugs which strongly and sequence-specifically bind to DNA.
      Compared with the behaviour of naked DNA, most of the complexes exhibit an
      increase in the critical EB/nucleotide binding ratio associated with the
      principal minimum in the sedimentation profile. Using netropsin (Nt) as the
      paradigm of the minor groove binders investigated, the drug-induced alterations
      in various structural parameters of both the relaxed and supercoiled form of DNA
      are described. Whereas winding number, helical repeat (both being defined with
      reference to a surface normal), and linking number of the superhelical DNA remain
      constant in our experiments, its twist number, surface twist, number of
      superhelical turns as well as the absolute values of linking number difference,
      superhelix density, and writhing number increase on binding of Nt.
      Correspondingly, compared with the naked relaxed DNA a higher linking number (or
      twist number, or winding number), a higher average duplex winding angle and a
      lower helical repeat have to be assigned to the relaxed Nt-DNA complex. The
      various minor groove binders investigated were found to differ considerably in
      their efficiency to alter the structure of supercoiled DNA.

PMID- 7524536
TI  - Specificity and editing by apoptosis of virus-induced cytotoxic T lymphocytes.
AB  - Recent studies have defined an immunological network by which the acute cytotoxic
      T-lymphocyte response to viral infection modulates or is modulated by the antigen
      load and by crossreactive memory T cells. Down regulation of the acute CTL
      response can be associated with either antigen-dependent or antigen-independent
      apoptosis, and the host enters a state of immune deficiency as these T cells
      become sensitized to apoptotic mechanisms.

PMID- 7524539
TI  - "Slim" nucleosides and nucleotides. I. Synthetic, structural and biophysical
      investigations of showdomycins.
AB  - A new, convenient, and short synthesis of 2'-deoxyshowdomycin, along with an
      improved procedure for the preparation of showdomycin, have been presented. A
      single-crystal X-ray structure of 1-benzyl-2'-deoxyshowdomycin (9) has been
      reported. Conformational studies using C.D. indicated that showdomycin exists
      predominantly in an anti conformation in aqueous solution. Molecular mechanics
      calculations using AMBER point to comparable binding energy of showdomycin
      adenosine pair with the natural uridine-adenosine pair, but with a significant
      base-ribose conformational deviation from the natural array in the former.
      Implications of such a conformational deviation on tumor and viral replications
      have been discussed. Base-pairing studies employing high resolution NMR
      spectroscopy indicate that both showdomycin and epishowdomycin base-pair with
      adenosine-5'-monophosphate (AMP); however, while showdomycin also shows evidence
      of stacking, that was absent in epishowdomycin. Molecular modeling studies using
      QUANTA/CHARMm show that showdomycin is capable of forming a homopolymer duplex by
      base-pairing with poly(A), but with a considerably broader and deeper major
      groove. A heteropolymer duplex with a single insert of showdomycin exhibits
      tighter coiling at the point of insertion. A ten-picosecond dynamics simulation
      of the above heteroduplex revealed relaxation of the helix with disruption of H
      bonding for two base pairs on either side of the insertion point, forming a large
      central cavity.

PMID- 7524540
TI  - Molecular dynamics simulations of a r(GA12G).d(CT12C) hybrid duplex.
AB  - RNA.DNA hybrid duplexes are relevant in various biological mechanisms like
      transcription and replication. Enzymes like RNase H cleave specifically the RNA
      strand in RNA.DNA duplexes. In antisense technology the complexation of mRNA with
      "modified" oligo(deoxy)-nucleotides leads to new hybrid duplexes. The knowledge
      about structure and dynamical behavior on an atomic level is fundamental for the
      understanding of any process involving hybrid duplexes. Therefore, molecular
      dynamics studies (200 picoseconds of trajectory) on a hybrid duplex structure
      r(GA12G).d(CT12C) were performed. During the stimulations, the deoxyribose
      residues assumed a puckering state between C2'-endo and C3'-endo, with an average
      mode around O4'-endo-C1'-exo, whereas the riboses of the RNA strand remained in
      the C3'-endo puckering domain. The results are compared to those obtained for the
      DNA.DNA duplex d(GA12G).d(CT12C) under identical simulation conditions. The DNA
      strand in the hybrid duplex behaves similar to that in a standard B-type DNA
      duplex. The helical parameters of the hybrid duplex however are closer to A- than
      to B-type. These observations suggest that RNA.DNA hybrid double helices are
      neither clearly A-form nor B-form. The furanoses in both strands can assume
      different puckering modes without the appearance of major geometrical
      constraints. The simulation results are in excellent agreement with recent
      experimental data.

PMID- 7524541
TI  - Transmission of zidovudine-resistant HIV-1 through heterosexual contacts.

PMID- 7524542
TI  - Rapid CD4+ cell decline after sexual transmission of a zidovudine-resistant
      syncytium-inducing isolate of HIV-1.

PMID- 7524543
TI  - How to overcome resistance of HIV-1 to HIV-1-specific reverse transcriptase
      inhibitors.

PMID- 7524544
TI  - Molecular fingerprinting of Salmonella typhimurium by IS200-typing as a tool for
      epidemiological and evolutionary studies.
AB  - The aim of this work was to develop and evaluate a molecular typing strategy for
      Salmonella based on hybridization of chromosomal DNA with two different probes
      derived from insertion sequence IS200. Probe IS200-TT was specifically
      constructed for this study as a trimer of a 112 pb TaqI-TaqI fragment of IS200.
      Among several restriction enzymes evaluated, two were selected: EcoRI, which cuts
      the insertion sequence in two pieces, each one complementary to one of the probes
      used, and PstI, a restriction enzyme with no recognition site into IS200. With
      several combinations of these restrictions enzymes and probes, 43 Salmonella
      typhimurium strains were analyzed for copy number and location of IS200, as well
      as reproducibility and stability of the patterns. IS200 types have been shown to
      be stable, both in strains isolated from different patients implicated in the
      same salmonellosis outbreak and in strains isolated from the same patient at
      different times or from different specimens. The discriminatory power of the
      method has been 0.91 to 0.94. As a comparison, S. typhimurium strains were also
      ribotyped. Discriminatory power of the ribotypes oscillated between 0.44 and
      0.55, depending on the enzyme used, and achieved a 0.78 value when the
      information obtained with two restriction enzymes was combined. Moreover, IS200
      typing was able to differentiate among a group of S. typhimurium strains which
      were identical by ribotype and enzymatic electrophoretic mobility. These results
      enable us to conclude that, for the stability, reproducibility and discriminatory
      power of the patterns generated, IS200 probes can be a very useful tool in the
      molecular typing of S. typhimurium.

PMID- 7524545
TI  - Multiple sclerosis: multiple etiologies, multiple genes?
AB  - Multiple sclerosis is a chronic inflammatory disease characterized by multifocal
      damage of the central nervous system myelin. Both humoral and cell-mediated
      immune abnormalities have been observed in patients with multiple sclerosis, but
      their relation to the demyelination process is not understood. The etiology of
      the disease is still unknown; however, evidence exists for an interplay between
      environmental and genetic factors. Several genes are involved in determining the
      disease susceptibility, at least one of them encoded within human leukocyte
      antigen gene complex. Other genomic regions coding for components of the immune
      system or myelin have also been suggested. Clinical, immunological and genetic
      data suggest that multiple sclerosis may turn out to be a heterogeneous disease.
      Therefore, molecular genetic dissection of this complex disease should provide
      important clues to its pathogenesis as well as unravel metabolic pathways for
      potential therapeutic or preventive strategies. This review will give an overview
      of recent progress and future challenges in identifying susceptibility genes for
      multiple sclerosis.

PMID- 7524546
TI  - Detection and characterization of atopic allergens.
AB  - The aim of the research of atopic allergens is to gather knowledge in order to be
      able to identify and to characterize environmental allergens and to develop
      better allergen preparations for diagnosis and treatment of IgE-mediated
      hypersensitivity diseases. Allergens or allergen activity can be detected and
      characterized with several in vivo and in vitro methods. In vivo tests measure
      the biological allergen activity, which is the most important characteristic of
      allergen preparations. Chemical and some immunochemical methods do not directly
      measure allergen activity, unless human IgE antibodies have been utilized. Since
      all these methods have their advantages and disadvantages, more than one method
      would be favourable in characterization of an allergen or an allergen
      preparation.

PMID- 7524548
TI  - [Hantavirus pulmonary syndrome (HPS)].

PMID- 7524547
TI  - Seroprevalence of hepatitis and HIV infection among rural pregnant women in
      Cameroon.
AB  - Since some hepatitis viruses and the human immunodeficiency viruses share common
      modes of transmission, such as the sexual route, we undertook to investigate the
      prevalence of antibodies to these and other pathogens among 384 rural pregnant
      women. Our study was intended to form the basis of infection management policies
      in pregnancy. Antibodies and other markers of the hepatitis A, B, C, and D
      viruses (HAV, HBV, HCV, HDV), the human immunodeficiency virus type 1 (HIV-1) and
      Treponema pallidum were sought. We tested for antibodies to the viruses using the
      appropriate enzyme-linked immunosorbent assays. HCV and HIV-1 infection were
      confirmed using standard immunoblotting techniques. Regarding HBV, we tested for
      the surface antigen (HBsAg), antibody to the surface antigen (anti-HBs) and
      antibody to the core antigen (anti-HBc). A non-specific test, the rapid plasma
      reagin test (RPR), was used for estimating Treponema pallidum (syphilis)
      infection. We found an overall prevalence of antibodies to HAV of 91.4%, to HCV
      of 6.8%, to HDV of 0%, and to HIV-1 of 3.5%. We found no IgM antibodies to HAV.
      The incidence of HBV markers was as follows: 5.4% for HBsAg, 61.3% for anti-HBs,
      and 84.6% for anti-HBc. RPR reactivity was found in 15.8% of the women. These
      results will be used to establish appropriate management and preventative
      policies for women attending the antenatal clinic. Prevention and appropriate
      early treatment of infections in these women will be considered.

PMID- 7524549
TI  - [Health status of the aged: study of a population sample].

PMID- 7524550
TI  - [Study on attitudes and practices of directors of drug addiction treatment
      centers regarding HIV infection prevention in drug addicts].

PMID- 7524552
TI  - [Pertussis vaccination: results of a KAP study of Apulia mothers].

PMID- 7524551
TI  - A survey on tuberculin reactivity of medical students in the Universities of
      Florence and Pisa (Italy).

PMID- 7524554
TI  - [General considerations and initial experiences concerning viral contamination of
      eastern Piedmont fresh waters].

PMID- 7524553
TI  - [Tiber environment and infections: antibodies to hantaviruses, Leptospira,
      Borrelia and hepatitis A virus in subjects active on the river banks].

PMID- 7524555
TI  - [Monitoring of halophilic vibrios in sea waters of the northern coasts of the
      province of Rome].

PMID- 7524556
TI  - [Procedure of endoscope disinfection in several Roman hospitals].

PMID- 7524557
TI  - [Control of endoscope disinfection procedures in a large Roman hospital].

PMID- 7524558
TI  - Identification of myelin-associated glycoprotein as a major myelin-derived
      inhibitor of neurite growth.
AB  - Contact-dependent axon growth inhibitory activity is present in CNS myelin, but
      the inhibitory proteins have not been fully characterized. We report here that at
      least two peaks of inhibitory activity can be separated by fractionating
      solubilized CNS myelin proteins by DEAE chromatography. A major peak of
      inhibitory activity corresponded to the elution profile of myelin-associated
      glycoprotein (MAG). Immunodepletion of MAG from these inhibitory fractions
      removed neurite growth inhibition, whereas recombinant MAG (ectodomain) was a
      potent inhibitor of neurite outgrowth. Immunodepletion of MAG from total extracts
      of CNS myelin restored neurite growth up to 63% of control levels. These results
      establish that MAG is a significant, and possibly the major, inhibitor in CNS
      myelin; this has broad implications for axonal regeneration in the injured
      mammalian CNS.

PMID- 7524559
TI  - The calcium feedback signal in the phototransduction cascade of vertebrate rods.
AB  - Intracellular free Ca (Cai) was measured in functionally intact rod outer
      segments in darkness and during light responses using the fluorescent Ca
      indicator Indo-dextran. In darkness, Cai was 554 +/- 25 nM (n = 28) for -85 +/- 2
      pA of circulating dark current (Id) and declined in saturating light to a minimum
      value of approximately 50 nM with a time course that paralleled the fall in
      Na:Ca,K exchange current. During a subsaturating flash response that reduced Id
      by 70%, Cai fell to a minimum of approximately 325 nM and recovered incompletely
      to a plateau of approximately 450 nM that lasted approximately 15 s after full
      recovery of Id. During a 60 s step that caused approximately 7-fold reduction in
      sensitivity of superimposed flash responses, Cai reached a steady-state level of
      approximately 252 nM.

PMID- 7524560
TI  - Identification of acetylcholine receptor channel-lining residues in the entire M2
      segment of the alpha subunit.
AB  - Each residue in and flanking the M2 membrane-spanning segment of the alpha
      subunit, from Glu-241 to Glu-262, was mutated to cysteine, and the mutant
      subunits were expressed together with wild-type beta, gamma, and delta subunits
      in Xenopus oocytes. Cysteines substituted for Glu-262, Leu-258, Val-255, Ser-252,
      Leu-251, Leu-250, Ser-248, Leu-245, Thr-244, and Glu-241 reacted with the
      positively charged, hydrophilic, sulfhydryl-specific reagent methanethiosulfonate
      ethylammonium (MTSEA), added extracellularly. These 10 residues, therefore, are
      exposed in the channel lumen. The pattern of exposure is compatible with an alpha
      helix, interrupted by an extended structure from Leu-250 to Ser-252.
      Acetylcholine caused subtle changes in the accessibilities of some of the
      engineered cysteines. Since all 10 residues are accessible to MTSEA in the closed
      state of the channel, the channel gate is at least as cytoplasmic as Glu-241, the
      most cytoplasmic of the residues tested.

PMID- 7524561
TI  - Identification of two cysteine residues that are required for redox modulation of
      the NMDA subtype of glutamate receptor.
AB  - Modulation of NMDA-mediated responses by oxidizing and reducing reagents has been
      described in a variety of neuronal preparations. Here, we report that NMDA-gated
      currents of oocytes expressing heteromeric NMDA receptors are also modulated by
      sulfhydryl redox reagents. Each cysteine residue in the NMDAR1 (NR1) subunit and
      each conserved NMDAR2 (NR2) cysteine residue in a prototypical subunit (NR2B) was
      tested for its role in redox modulation. We have identified 2 cysteines in the
      NR1 subunit that are required for redox modulation of NMDA-gated currents in
      oocytes expressing NR1-NR2B, NR1-NR2C, or NR1-NR2D receptors. Mutation of these
      same 2 cysteines also eliminated potentiation by spermine and shifted the IC50
      for H+ inhibition and the EC50 for NMDA. Redox modulation of heteromeric NR1-NR2A
      receptors appeared to be different from that of the other heteromeric receptors,
      indicating the presence of one or more unique redox modulatory sites on NR1-NR2A
      receptors.

PMID- 7524562
TI  - A GABA transporter operates asymmetrically and with variable stoichiometry.
AB  - Membrane currents produced by the expression of a rat GABA transporter (GAT-1)
      stably transfected into HEK293 cells were characterized with a whole-cell voltage
      clamp. Three modes of function were identified: ex-gated currents produced by
      extracellular GABA, in-gated currents produced by intracellular GABA, and
      uncoupled currents produced in the absence of GABA. The ex-gated current was not
      the reversal of the in-gated current; moreover, the stoichiometry between GABA
      and co-ions was not always fixed. Each mode of function required a different set
      of ions on the two sides of the membrane. We made rapid solution changes and
      observed an allosteric effect of Na+ that only occurred at the extracellular
      surface. Thus, the GAT-1 transporter does not behave like a recirculating carrier
      but may be described as a pore with ion gates at either end that are controlled
      in part by allosteric sites.

PMID- 7524563
TI  - Control of transmitter release from retinal amacrine cells by Ca2+ influx and
      efflux.
AB  - Cultured retinal amacrine cells show quantal GABAergic synaptic transmission.
      Voltage clamping pre- and post-synaptic cells of an isolated pair has allowed us
      to examine the entry and removal of Ca2+ at synaptic terminals. Brief presynaptic
      Ca2+ currents elicit an initial postsynaptic current that probably reflects the
      roughly synchronous exocytosis of docked vesicles. Prolonged Ca2+ currents elicit
      an additional second phase of release whose time course can greatly exceed that
      of the presynaptic voltage step. The time course of this second phase reflects a
      sustained increase in cytosolic Ca2+ and is matched closely by the activity of
      the presynaptic Na-Ca exchanger, as revealed by an exchange current. Eliminating
      the activity of the exchanger by removal of external Na+ prolongs this second
      phase of transmission greatly. Because transmitter release at these synapses
      outlasts Ca+ channel opening, Na-Ca exchange plays a significant role in shaping
      transmission.

PMID- 7524565
TI  - Reactions of human keratinocytes in vitro after application of nicotine.
AB  - Nicotine is rapidly taken up by human keratinocytes (HaCaT cells) and after 3 h
      the uptake is approximately 50% of maximum. Cotinine, a metabolite of nicotine,
      was detected, thus demonstrating the metabolism of nicotine in HaCaT cells. Low
      nicotine concentrations (0.1-200 micrograms/ml) did not influence the
      incorporation rate of thymidine into DNA or amino acids into proteins. Inhibition
      of DNA and protein synthesis was only observed at concentrations > 200
      micrograms/ml. After application of 400 micrograms/ml nicotine, the cells were
      vacuolated. This process was reversed after nicotine withdrawal. At low nicotine
      concentrations, no changes in microtubules and actin filaments could be detected.
      However, in the presence of nicotine (1-10 micrograms/ml), keratin filaments
      showed a more orderly pattern that controls, and the expression of the suprabasal
      keratins 1 and 10/11 was induced and increased according to the concentration of
      nicotine. The number of cornified envelopes also increased markedly. Nicotine
      concentrations > 100 micrograms/ml led to a disarrangement of keratin filaments
      and to a decrease in keratin expression and cornified envelope formation. Our
      results suggest that nicotine at concentrations up to 100 micrograms/ml is not an
      irritant but may induce cornification of the skin.

PMID- 7524564
TI  - Inhibition of hippocampal heme oxygenase, nitric oxide synthase, and long-term
      potentiation by metalloporphyrins.
AB  - Four potent metalloporphyrin inhibitors of heme oxygenase were used to assess
      whether carbon monoxide production was required for induction of LTP in the CA1
      region of the hippocampus. Although the metalloporphyrins produced a similar and
      substantial inhibition of heme oxygenase activity in hippocampal slices, only two
      compounds reduced the amount of LTP elicited by tetanic stimulation (chromium
      mesoporphyrin IX and zinc protoporphyrin IX). Both chromium mesoporphyrin IX and
      zinc protoporphyrin IX inhibited nitric oxide synthase in the hippocampus; tin
      mesoporphyrin IX and zinc deuteroporphyrin IX bis glycol neither reduced LTP
      induction nor inhibited NOS activity, although they did inhibit heme oxygenase.
      None of these metalloporphyrins reversed established LTP. Thus, together these
      data do not support carbon monoxide as a mediator in either LTP induction or
      expression/maintenance and emphasize further the nonselectivity of some
      metalloporphyrins.

PMID- 7524566
TI  - Expression of transforming growth factor-alpha and epidermal growth factor
      receptor is increased following bleomycin-induced lung injury in rats.
AB  - To investigate the potential role of transforming growth factor-alpha (TGF-alpha)
      and the epidermal growth factor receptor (EGF-R) in the fibroproliferative
      response to acute lung injury, we determined lung steady-state TGF-alpha and EGF
      R mRNA levels, TGF-alpha protein levels, and the distribution of TGF-alpha and
      EGF-R immunoreactive protein of bleomycin-injured and control rat lungs. At 2 and
      4 days after a single intratracheal injection of bleomycin, TGF-alpha mRNA levels
      increased to 159% and 184% of control values, respectively. EGF-R mRNA levels
      increased to 163%, 314%, and 170% of control values at 1, 7, and 14 days after
      bleomycin instillation. TGF-alpha protein levels in whole lung extracts increased
      to 230% of control values at 4 days after bleomycin administration. TGF-alpha and
      EGF-R immunoreactivity was detected in macrophages, alveolar septal cells, and
      airway epithelium of control and bleomycin-injured animals with an apparent
      increase in the intensity and number of specifically immunostained cells
      following lung injury. TGF-alpha and EGF-R immunoreactive proteins were detected
      in foci of cellular proliferation and in areas of intraalveolar fibrosis. We
      conclude that TGF-alpha and the EGF-R are present in normal and bleomycin-injured
      rat lung and that the expression of this growth factor and its receptor are up
      regulated following lung injury. These results suggest that increased expression
      of TGF-alpha and the EGF-R may be an important mechanism that modulates the
      fibroproliferative response to acute lung injury.

PMID- 7524569
TI  - For better or for worse: does stem cell factor importantly regulate mast cell
      function in pulmonary physiology and pathology?

PMID- 7524567
TI  - Hepatocyte growth factor is a growth factor for rat alveolar type II cells.
AB  - Proliferation of alveolar type II cells is thought to be critical for restoration
      of gas exchange units after diffuse alveolar damage. However, the factors that
      regulate type II cell proliferation are not well understood. Hepatocyte growth
      factor (HGF) is a potentially important mitogen because it causes epithelial
      cells but not fibroblasts to proliferate and is found in the lung. We used rat
      alveolar type II cells in primary culture to demonstrate that HGF stimulates DNA
      synthesis in a concentration-dependent manner. The half maximal effect on
      stimulation of thymidine incorporation was less than 1 ng/ml. By autoradiography,
      HGF increased nuclear labeling from 1.3% of type II cells with medium alone to
      9.4% with 5 ng/ml HGF. During this time, HGF modestly increased cell number in
      comparison to control media. However, in an assay of colony formation in low
      density cultures, HGF did not consistently increase colony formation by alveolar
      type II cells and was less effective than acidic fibroblast growth factor or
      bronchoalveolar lavage fluid in this assay. The receptor for HGF (c-met proto
      oncogene) was expressed in rat type II cells and whole lung but not in
      macrophages. In contrast, the mRNA for HGF was detected in rat macrophages and
      lung but not in type II cells. However, HGF message was not detected in human
      alveolar macrophages under conditions in which the HGF message was detected in
      rat alveolar macrophages and in human fibroblasts. Hence, HGF is a potential
      paracrine growth factor for alveolar type II cells, but there may be important
      species differences in the relative level of expression.

PMID- 7524568
TI  - Nitric oxide inactivates xanthine dehydrogenase and xanthine oxidase in
      interferon-gamma-stimulated macrophages.
AB  - Interferon-gamma (IFN-gamma) has been reported to up-regulate transcription of
      the xanthine dehydrogenase (XDH) gene and to regulate XDH and xanthine oxidase
      (XO) activity in endothelial cells and liver tissue. Macrophages are a source of
      XDH/XO activity at inflammatory sites and are functionally regulated by IFN
      gamma. We studied the effect of IFN-gamma on XDH and XO in rat bone marrow
      macrophages, rat alveolar macrophages, and murine RAW cells. Instead of an
      induction of enzyme activity, XDH/XO activity was almost totally lost after
      incubation with 100 to 1,000 U/ml of IFN-gamma for 24 h in all three cell types.
      The loss of cell-associated XDH/XO activity was not correlated with the
      appearance of XDH/XO activity in the media. In addition, the loss of XDH/XO
      activity could not be accounted for by transcriptional repression, since there
      was an increase in steady-state levels of XDH mRNA. To determine whether XDH/XO
      activity might be lost through nitric oxide-mediated inactivation of XDH/XO, we
      compared the time course and dose response for XDH/XO inactivation with that of
      nitric oxide production and found them similar. Treatment with the nitric oxide
      inhibitor N-monomethyl arginine appeared to totally block inactivation of XDH/XO
      by IFN-gamma. We conclude that upon stimulation with IFN-gamma, inducible nitric
      oxide in macrophages leads to post-transcriptional inhibition of XDH/XO, possibly
      minimizing the potential for tissue injury from XO released from macrophages into
      the inflammatory milieu. Inactivation of XDH may represent yet another
      "protective" role for nitric oxide at sites of inflammation.

PMID- 7524570
TI  - Recombinant stem cell factor-induced mast cell activation and smooth muscle
      contraction in human bronchi.
AB  - The effect of human recombinant stem cell factor (SCF) on inflammatory mediator
      release and smooth muscle contraction was evaluated in human isolated intralobar
      bronchi. Bronchi from 21 of 26 donors contracted in response to SCF. The
      threshold concentration was approximately 0.01 micrograms/ml. At 1 micrograms/ml,
      the tissues contracted to about 60% of the carbamylcholine-induced maximum
      contraction. The responses to SCF mimicked those obtained with anti-IgE. Thus,
      the contractions to SCF and anti-IgE were inhibited to a similar extent by a
      combination of a cysteinyl-leukotriene receptor antagonist and a histamine H1
      receptor antagonist. SCF also mimicked the effect of anti-IgE in releasing
      histamine, i-LTD4, and PGD2 from the bronchi. At a threshold concentration for
      contraction (0.01 micrograms/ml), SCF had no effect on subsequent responses to
      anti-IgE in the bronchi. The data suggest that human recombinant SCF contracts
      airway smooth muscle by stimulating the release of contractile mediators from
      bronchial mast cells. The data fail to support the hypothesis that SCF primes
      bronchial mast cells to subsequent immunologic stimuli.

PMID- 7524571
TI  - Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat
      alveolar macrophages.
AB  - The present study was undertaken to determine whether asbestos exposure induces
      the formation of nitric oxide (NO.) radical by rat alveolar macrophages (AM). For
      this purpose, AM from Sprague-Dawley rats were cultured for 48 h in the presence
      or absence of either chrysotile (serpentine) or crocidolite (amphibole) asbestos
      fibers. The effects of asbestos fibers were compared with those of nonfibrogenic
      carbonyl iron particles. Nitrite (NO2-), the stable oxidation product of NO. in
      macrophage conditioned medium, was assayed by the Griess reaction. Production of
      NO2- by AM was significantly increased by both chrysotile (P < 0.01) and
      crocidolite (P < 0.05) asbestos fibers (10 micrograms/ml). Since interferon-gamma
      (IFN-gamma) is known to induce NO. synthase within macrophages, and since
      elevated levels of intrapulmonary IFN-gamma have been noted in asbestos workers,
      the combined effects of asbestos and IFN-gamma also were studied in the context
      of NO. formation. Addition of IFN-gamma (250 to 500 IU/ml) synergistically
      enhanced the formation of NO2- induced by chrysotile and crocidolite. Notably,
      carbonyl iron had no significant effect on NO. production by AM. NO2- production
      was significantly attenuated by the NO. synthase inhibitor, NG-monomethyl-L
      arginine (0.5 to 1 mg/ml). By contrast, superoxide dismutase (150 U/ml)
      significantly enhanced asbestos-induced NO2- production by AM (P < 0.001). Since
      superoxide anion can interact with NO. to generate the toxic hydroxyl radical,
      and since superoxide dismutase is known to protect against asbestos-induced
      injury, the induction of NO. radical by asbestos fibers may represent a novel
      form of asbestos-related injury.

PMID- 7524573
TI  - Synergistic induction of alpha 2-macroglobulin synthesis by fibroblast growth
      factor-2 and transforming growth factor beta 1 in bovine adrenocortical cells.
AB  - We report here that basic fibroblast growth factor (FGF-2), a potent mitogen for
      adrenocortical cells, stimulates the expression of alpha 2-macroglobulin by these
      cells at a transcriptional level and is synergistic with TGF beta 1 for this
      effect. This is supported by the following observations: (i) Treatment of
      adrenocortical cells by FGF-2 resulted in a time-dependent and dose-dependent
      increase of alpha 2M synthesis, (ii) FGF-2 did not modify alpha 2M secretion
      rate; (iii) The induction of alpha 2M synthesis by FGF-2 was not observed in the
      presence of the transcription inhibitor DRB; (iv) The amount of alpha 2M mRNA was
      increased by 2 to 3 fold under either FGF-2 or TGF beta 1 treatment; (v) Optimal
      doses of TGF beta and FGF-2 synergistically increased alpha 2M synthesis. Since
      alpha 2M is a growth factor-binding protein, its regulation by FGF-2 may
      represent an important feedback mechanism controlling the bioactivity of
      autocrine regulators (FGF-2, TFG beta) of adrenocortical functions.

PMID- 7524572
TI  - Defective pulmonary recruitment of neutrophils in a rat model of endotoxemia.
AB  - We have characterized a defect in the pulmonary recruitment of neutrophils (PMNs)
      in rats with experimental endotoxemia. Rats pretreated with intravenous (IV) 0.9%
      saline (NaCl) showed abundant PMNs in bronchoalveolar lavage (BAL) fluid after
      intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) (54.27 +/- 9.80 x 10(6), n
      = 7, versus IT saline, 0.73 +/- 0.62 x 10(6), n = 4). In contrast, endotoxemic
      rats (IV LPS 1.0 mg/kg) failed to show PMN influx after IT LPS (0.40 +/- 0.13 x
      10(6) PMNs in BAL fluid, n = 7). Four hours after the IT administration of LPS,
      the chemotactic activity of BAL fluid from endotoxemic rats (87 +/- 9.92% of
      maximal chemotaxis toward zymosan-activated serum [ZAS], n = 4) was not
      significantly different (P > 0.05), from rats pretreated with IV NaCl (61.09 +/-
      6.17% of maximal chemotaxis toward ZAS, n = 4). Endotoxemic and control rats
      showed similar chemotactic gradients in determinations of the BAL/plasma
      chemotactic activity ratio (BAL/plasma ratio: 2.16 +/- 0.14, n = 4, IV NaCl
      versus 2.98 +/- 0.14, n = 4, IV LPS, P > 0.05). Serum from untreated rats, rats
      pretreated with IV NaCl, and endotoxemic rats caused minimal effects on rat PMN
      chemotaxis in vitro (78.17 +/- 8.16%, 79.29 +/- 7.09%, and 69.28 +/- 9.04% of
      maximal chemotaxis toward ZAS, respectively, n = 4/group, P > 0.05). Quantitation
      of PMN adhesion molecules revealed a loss of L-selectin (8 +/- 5% of control
      group, n = 3), an increase in Mac-1 (776 +/- 82.60% of control group, n = 3), and
      no change in LFA-1 when normal PMNs were incubated with plasma from rats
      pretreated with IV LPS (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524574
TI  - Altered expression of insulin-like growth factor-I (IGF-I) and IGF binding
      proteins during rat thyroid hyperplasia and involution.
AB  - We have investigated changes in the synthesis and localization of insulin-like
      growth factor (IGF)-I and IGF binding proteins (IGFBPs) in thyroid tissues during
      the induction of goitre in iodine-deficient rats, and during the subsequent
      involution of the gland following goitrogen withdrawal. Goitre was induced in
      adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of
      methimazole together with a low iodine diet. After twelve weeks the goitrogenic
      stimuli were removed and thyroids examined 4 weeks later. Circulating T4 levels
      became undetectable within two weeks of goitrogen administration while thyroid
      weight had increased five-fold. The thyroids continued to increase in size up to
      10 weeks, but at a slower growth rate. IGF-I mRNA, detected by ribonuclease
      protection assay, was present in the control rat thyroid and increased in
      abundance after both 1 and 2 weeks of goitrogen administration. Levels of IGF-I
      mRNA showed a relative decline with prolonged goitrogen administration, and
      following thyroid involution the hybridization signal was similar to that seen in
      control glands. Northern blot hybridization showed that IGFBP-2, -3 and -5 mRNAs
      were all present in growth-quiescent, control thyroids and those encoding IGFBP-2
      and -3 were elevated in the goitrous glands and remained so as long as goitrogen
      was administered, thereafter declining during thyroid involution. IGF-I and IGFBP
      2 and -3 mRNAs and synthesized peptides, detected by in situ hybridization and
      immunohistochemistry respectively, were found to co-localize predominantly in
      follicular epithelial cells. IGFBP-5 mRNA abundance was unaltered during goitre
      formation, but was increased in the involuting thyroid. Both IGFBP-5 mRNA and
      peptide were localized to the parafollicular cells (C-cells) which were increased
      in number during involution. The results suggest that an increased expression of
      IGF-1 may contribute to early goitre formation, but that a relative increase in
      the abundance of IGFBP-2 and -3 may limit IGF availability at later times, and
      facilitate a slowing of thyroid growth rate. The discrete expression of IGFBP-5
      by C-cells suggests that it could contribute indirectly to goitre formation or
      involution by acting in a paracrine fashion.

PMID- 7524575
TI  - Acute non-lymphocytic leukaemia complicating gastric cancer treated with
      epipodophyllotoxin containing chemotherapy and G-CSF.

PMID- 7524576
TI  - Bacterial phylogeny based on 16S and 23S rRNA sequence analysis.
AB  - Molecular phylogeny increasingly supports the understanding of organismal
      relationships and provides the basis for the classification of microorganisms
      according to their natural affiliations. Comparative sequence analysis of
      ribosomal RNAs or the corresponding genes currently is the most widely used
      approach for the reconstruction of microbial phylogeny. The highly and less
      conserved primary and higher order structure elements of rRNAs document the
      history of microbial evolution and are informative for definite phylogenetic
      levels. An optimal alignment of the primary structures and a careful data
      selection are prerequisites for reliable phylogenetic conclusions. rRNA based
      phylogenetic trees can be reconstructed and the significance of their topologies
      evaluated by applying distance, maximum parsimony and maximum likelihood methods
      of phylogeny inference in comparison, and by fortuitous or directed resampling of
      the data set. Phylogenetic trees based on almost equivalent data sets of
      bacterial 23S and 16S rRNAs are in good agreement and their overall topologies
      are supported by alternative phylogenetic markers such as elongation factors and
      ATPase subunits. Besides their phylogenetic information content, the differently
      conserved primary structure regions of rRNAs provide target sites for specific
      hybridization probes which have been proven to be powerful tools for the
      identification of microbes on the basis of their phylogenetic relationships.

PMID- 7524577
TI  - Suicidal inhalation of vehicular exhaust in the Lothian and Borders region of
      Scotland.
AB  - 1. A 6-year retrospective study of the features of 79 consecutive completed
      suicides from exhaust fume inhalation (SEFI) in the Lothian and Borders region of
      Scotland was conducted. Full forensic autopsies with histological and
      toxicological studies were carried out. 2. The mean incidence is 2.0/100,000
      population (M = 3.7; F = 0.4; P <> 0.001); increasing since 1990. The age peak is
      in the 35-44 years age group (especially among males) and a significant (P <
      0.001) proportion reside in rural areas. 3. SEFI is significantly (P < 0.05)
      higher during spring and summer; outdoor locations are prevalent during summer.
      4. Most (75.6%) of the victims were in current employment. Psychiatric illness
      (30.7%), problems in marriage or relationships (28.2%) and financial difficulties
      (16.7%) were the major associated socio-medical factors. 5. The mean
      carboxyhaemoglobin (COHb) saturation was 74 +/- 11.2%; fatal COHb saturation
      levels were still detectable in severely decomposed bodies. The blood alcohol
      concentration (BAC) in 37 of the victims ranged from 14-397 mg dl-1. No
      significant correlation exists between COHb saturation and the victim's age or
      BAC. 6. Attempts to reduce the incidence of SEFI must be directed principally to
      dealing with associated sociomedical problems. The reduction of the potential of
      vehicles to produce carbon monoxide and of directing exhaust fumes into the
      interior of the vehicle are important secondary preventative measures.

PMID- 7524578
TI  - Nitric oxide synthases: why so complex?

PMID- 7524579
TI  - Intensive chemotherapy with high-dose epirubicin every 2 weeks and prophylactic
      administration of filgrastim in advanced breast cancer.
AB  - 50 women with advanced breast cancer were treated with an intensified regimen
      which consisted of high-dose epirubicin (110 mg/m2) every 2 weeks and filgrastim
      (5 micrograms/kg) subcutaneously for 13 days, starting 24 h after chemotherapy.
      44 patients completed all six cycles. The median interval between cycles of
      treatment was 14.3 days. The actually administered median dose per unit time per
      patient was 53 mg/m2/week, amounting to 97.2% of the dose prescribed by the
      protocol. 7 [14%, 95% confidence interval (C.I.) 4-24%] patients achieved a
      complete and 25 (50%, 95% C.I. 36-64%) a partial response. Median time to
      progression was 32 weeks and median survival 64 weeks. Stomatitis and fever each
      occurred in 7 (14%) patients. Grade 3 haematological toxicity was observed in 6
      (12%) patients. 1 (2%) patient developed grade 4 cardiac toxicity. This
      intensified regimen appears to be a well tolerated and effective treatment in
      advanced breast cancer.

PMID- 7524581
TI  - Compartment pressure in the carpal tunnel in distal fractures of the radius. A
      prospective study.
AB  - In a prospective controlled study, carpal tunnel tissue pressures were determined
      in a group of 56 patients with distal dislocated fractures of the radius at
      initial presentation, immediately prior to and after reduction, and 1, 2, 4, 12,
      and 24 h after reduction. Depending on the severity of the trauma and delay to
      presentation at the hospital, initial measurements revealed raised pressure
      averaging 23 mm Hg, which further increased during reduction to 44 mm Hg. After 4
      h the average pressure was 37 mm Hg, and it then dropped to 26 mm Hg after 12 h.
      For anatomical reasons the median nerve is quite vulnerable in the region of the
      wrist joint. Chronic pressure here may cause carpal tunnel syndrome. Acute
      pressure in the carpal tunnel, which according to our investigations represents a
      distinct compartment, results in an overt compartment syndrome. The possibility
      of a direct relationship between markedly elevated tunnel pressure and the
      development of Sudeck's dystrophy is discussed.

PMID- 7524582
TI  - [Stabilization-interposition arthroplasty in peri-trapezial arthritic lesions.
      Apropos of a prospective series of 200 cases].
AB  - A group of 200 arthroplasties (180 patients) for basal thumb arthrosis is
      reported. The used technique is similar to that described by Burton and Pelegrini
      in 1986. At the last follow up (2 years minimum), 90% patients were without pain,
      95% were very satisfied, the grip strength was improved in 70%, and the
      shortening of the thumb was between 2 and 9 mm (mean 6 m). The mobility of the
      first metacarpal is improved in only 47%. Complications were limited to two NAD
      for patients operated of carpal tunnel syndrome in the same time.

PMID- 7524583
TI  - [Endoscopic decompression of the median nerve in the carpal tunnel. Apropos of
      1,400 cases].
AB  - We report the results of endoscopic carpal tunnel release in 1,400 patients over
      a two year period (minimum 6-month follow-up). All patients were operated on
      using a technique derived from that of Chow. Complications were limited to two
      partial lesions of the superficial palmar arch and one interdigital nerve lesion.
      The technique is described. Analysis of the results indicates the advantages of
      this method. Though immediate post-operative comfort was greater and restoration
      of the grip quicker, the results were roughly similar to those of the classic
      method in the 6 months following surgery. Sympathetic dysfunction represented
      only 0.28% of cases. Patients generally returned to work earlier than with the
      classic technique. This method does not replace the conventional technique for
      certain indications. The authors emphasize the difficulties involved and
      recommend that this method be used only by experienced surgeons and aware of
      intra-operative risks.

PMID- 7524584
TI  - [Anatomy of the lymphatic system of the arm].
AB  - The lymphatic system of the upper limb is studied according to its various
      networks: superficial, deep, axillary lymph nodes and anastomotic system. The
      most important superficial lymphatic system is described in the upper limb
      together with its applications for manual lymphatic drainage. The microstructure
      and function of the lymphatic system are studied. The pathophysiology and manual
      and microsurgical treatments of lymphoedema are not discussed in this article.

PMID- 7524580
TI  - Metastatic instability at the proximal end of the femur. Comparison of
      endoprosthetic replacement and plate osteosynthesis.
AB  - A retrospective study was performed of the surgical treatment of metastatic
      lesions of the proximal femur in 50 patients. In 25 consecutive cases a
      megaprosthesis was implanted; compound plate osteosynthesis was performed in
      another 25 consecutive patients. Indications for surgical treatment were
      pathological fractures or, for prophylactic treatment, lesions of the femoral
      cortex exceeding 2.5 cm in diameter or affecting half the diameter of the bone or
      more. In all patients capable of walking preoperatively mobility was regained.
      Immediate full weight-bearing stability was obtained in all patients. Group
      analysis showed that the functional rating of the hip joint was unchanged, i.e.,
      good or excellent, in all patients with compound osteosynthesis, compared to only
      68% in the endoprosthesis group. Pain relief was excellent or good in 84% and 88%
      respectively. Dislocation of the tumor prosthesis occurred in 3 patients. Closed
      reduction was possible in 2 cases. Local recurrence was higher in the patients
      undergoing plate osteosynthesis, as was the frequency of tumor-related implant
      failure. Postoperative survival averaged 14.7 months and 12.1 months
      respectively.

PMID- 7524585
TI  - [Solitary carpal osteochondroma. Apropos of a case].
AB  - A bone tumor appeared progressively on the back of the wrist of a 62-year-old
      woman. Clinical and radiological aspects suggested a chondroma or chondrosarcoma.
      However, this was a solitary carpal osteochondroma arising from the capitate
      bone. The authors discuss the various features of this benign tumor.

PMID- 7524587
TI  - [Lawsuits in medical liability. Why? Against whom?].
AB  - The author, a Surgical Expert at the french Supreme Court, gives his opinion
      about medical liability in malpractice action. He studies successively: the main
      causes of these actions: lack of information, poor results, loss of confidence on
      the part of the patients, comments from other doctors; malpractice liability
      needs a relation between the surgical act and the damage; French law concerning
      State owned Hospitals; future projects concerning compensation without liability.
      The various channels which can be used in malpractice trials are successively
      examined and also the surgeons attitude in relation to his lawsuit.

PMID- 7524588
TI  - [Giant cell tumor of the tendon sheath of the long extensor muscle of the thumb
      in a 7-year-old child].
AB  - The authors report the case of a giant cell tumour of the flexor pollicis longus
      tendon sheath in a child. This benign tumour, usually observed in women between
      the ages of 30 to 50 years, has a highly controversial aetiopathogenesis; the
      existence of initial trauma is found in 50% of cases. The present case concerns a
      7-year-old girl with swelling of the right thumb for two years. Surgical
      resection established the definitive diagnosis by histological examination of the
      specimen. The follow-up is currently two years, with no local recurrence.

PMID- 7524589
TI  - An approach to the diagnosis of chronic wrist pain.
AB  - A clinical algorithm was developed to help establish a diagnosis in patients with
      chronic wrist pain. The accuracy of the algorithm was examined in a prospective
      blind study of 40 patients presenting to the Hand Unit with undiagnosed wrist
      pain and compared with the later findings at arthroscopy, which were believed to
      be as accurate as currently possible. Using simple examination techniques and
      conventional radiographs, an accurate diagnosis was made in 80% of cases.
      Examination techniques including the scapho-lunate shear test and the presence of
      local tenderness or pseudostability were found to be particularly accurate.

PMID- 7524586
TI  - [Mucoid cysts of the distal interphalangeal joints of the fingers. Apropos of a
      prospective series (100 cases)].
AB  - 100 mucous cysts of distal interphalangeal joint were treated by a radical
      excision that involved skin, cyst and dorsal capsular structures. The follow up
      was 2 years minimum, only two recurrence were noted, with other procedure the
      tate of recurrence is higher (10 to 20%). The proposed procedure is based on two
      hypothegenesis: skin localisation of mucous jelly, and degeneration of dorsal
      capsular structure of an arthritic joint.

PMID- 7524590
TI  - A rare case of carpal dislocation.
AB  - We present a rare case of carpal perilunate fracture-dislocation, with volar
      displacement of the distal carpal row and a proximal row location of the
      triquetrum. A pre-existing abnormal radio-luno-capitate alignment might have
      contributed to both the unusual volar direction and the difficulty encountered in
      its treatment, which caused us to perform a radiocarpal K-wire transfixation.

PMID- 7524591
TI  - [The efficacy of naftidrofuryl on unexpected autonomic symptoms following carpal
      tunnel surgery].
AB  - Symptoms of sympathetic lability occur 30 days after carpal tunnel surgery in
      about 2.6% cases. A double-blind placebo controlled clinical trial of
      naftidrofuryl was conducted in 195 patients. It demonstrated that these symptoms
      occur during the two-week-period after surgery, and that some patients are
      particularly exposed to an unexpected course (i.e. women and more than 50 years)
      during the third and fourth weeks after surgery. In this study, patients treated
      with naftidrofuryl showed a reduction of some symptoms of sympathetic lability,
      and stabilisation of the unfavourable course observed in patients with placebo;
      this preventive efficacy of naftidrofuryl could be due to its 5-HT2 receptor
      blocking action, which is responsible for vasoconstriction and platelet and
      erythrocytes aggregation. Naftidrofuryl though improves arteriolar haemodynamics,
      limiting the development of pain and oedema.

PMID- 7524593
TI  - Antiproteasic activity of C1 inhibitor. Therapeutic perspectives.
AB  - Kallikrein is a protease involved in the inflammatory process causing acute
      pancreatitis. Attempts to prevent this process with antiprotease agents have been
      successful in experimental animal models but disappointing in humans. We studied
      40 consecutive patients undergoing endoscopic papillosphincterotomy. This
      procedure can induce a transient, moderate pancreatic inflammatory reaction,
      characterized by hyperamylasemia, which in 1-6% of the patients may evolve to
      acute pancreatitis. To assess the capacity of C1 inhibitor, the main
      physiological inhibitor of kallikrein, to prevent such complications, we
      pretreated 20 patients with 3000 U of C1 inhibitor plasma concentrate i.v.; 20
      patients served as controls. Serum levels of amylase and functional C1 inhibitor
      were determined before the procedure and after 2, 4, 8 and 24 hours. Serum levels
      of amylase in the control group (146 +/- 21 IU) and in the group treated with C1
      inhibitor (158 +/- 25 IU) were similar before treatment. Four and 8 hours after
      the end of the procedure, amylase levels were significantly lower (p < 0.001) in
      the treated group (231 +/- 46 and 355 +/- 104 IU) than in the control subjects
      (969 +/- 229 and 923 +/- 207 IU). After 24 hours both groups had normal amylase
      levels. In treated patients, functional levels of C1 inhibitor increased from 104
      +/- 30 to 175 +/- 30% and remained elevated throughout the observation period.
      These data indicate that C1 inhibitor plasma concentrate can prevent
      hyperamylasemia following pancreas injury, probably, by inhibiting the kallikrein
      mediated inflammatory process. C1 inhibitor might benefit patients at high risk
      of pancreatitis who undergo endoscopic papillosphincterotomy.

PMID- 7524595
TI  - Lindane affects phosphoinositide turnover through a different mechanism of the
      phosphatidylinositol synthesis inhibition in rat renal proximal tubule cell
      culture.
AB  - The ability of lindane to change the metabolism of inositol phospholipids was
      investigated using rat renal proximal tubular cell cultures labelled with
      [3H]inositol. Lindane addition to the culture medium caused labelling of inositol
      trisphosphate, inositol bisphosphate and inositol tetrakisphosphate to decrease
      and that of the inositol monophosphate pool to increase. A depletion of
      radioactivity in phosphatidylinositols was also observed after lindane addition.
      Most strikingly, the addition of lindane considerably increased the levels of
      glycerophosphoinositol in a dose-dependent manner. The effect of lindane follows
      a different pattern from that of bradykinin, and it is suggested to act by
      stimulating phospholipase A activity(ies).

PMID- 7524596
TI  - Phorbol esters showing selective activation of PKC isozymes in vitro regulate
      thyroid function and insulin-like growth factor binding protein secretion.
AB  - We have examined the effects of phorbol derivatives which show selective
      activation of protein kinase C (PKC) isozymes in vitro, on several parameters of
      thyroid function. Functions examined were iodide uptake and organification,
      iodocompound secretion and insulin-like growth factor binding protein (IGFBP)
      secretion, all of which have been shown previously to be modulated by 12-O
      tetradecanoylphorbol 13-acetate (TPA), a pan activator of PKC isozymes. All of
      the agents examined, including DOPPA (12-deoxyphorbol-13-O-phenylacetate-20
      acetate), which is specific for the beta 1 isozyme in vitro, were able to mimic
      the effects of TPA. These effects were evident by 2 h in the iodide uptake and
      organification assays, by 4 h in the secretion assays and by 8 h in the IGFBP
      secretion assays. The phorbol derivatives differed from TPA in their ability to
      down-regulate total PKC activity, DOPPA being weakly effective at 8 h (14.7%
      inhibition) when TPA had effected > 70% down-regulation of PKC. As the effects of
      DOPPA were detected by 8 h at the latest, these data indicate that the effects
      observed were due to PKC activation rather than down-regulation. Furthermore, the
      differences in down-regulation profiles between DOPPA and TPA suggest that in
      vivo, DOPPA may maintain its in vitro specificity. We conclude that inhibition of
      thyroid iodide uptake and its organification, stimulation of iodocompound
      secretion and stimulation of IGFBP-2 and IGFBP-3 secretion may be effected
      through the modulation of a limited number of PKC isozymes and possibly
      initially, only through PKC beta 1.

PMID- 7524592
TI  - Use of aprotinin in knee replacement surgery.
AB  - We have studied the effect of aprotinin on blood loss and subsequent blood
      transfusion in 17 patients undergoing knee replacement surgery. Patients
      receiving aprotinin (total dose 2,000,000 kallikrein inhibiting units) received
      fewer units of blood than control patients (P < 0.05), although there was no
      significant difference in blood loss between the two groups. The study was
      stopped when one patient in the aprotinin group needed an above-knee amputation
      because of ischaemia secondary to arteriovenous thrombosis after knee replacement
      surgery. Although the patient had peripheral vascular disease which could have
      accounted for the thrombosis, the role of aprotinin under tourniquet conditions
      is unclear.

PMID- 7524598
TI  - Dithio-bis-mercaptoethanesulphonate (DIMESNA) does not prevent cellular damage by
      metabolites of ifosfamide and cyclophosphamide in LLC-PK1 cells.
AB  - Ifosfamide (IF) is an alkylating cytostatic with urotoxic (haemorrhagic cystitis)
      and nephrotoxic (Fanconi syndrome) side effects. Cyclophosphamide (CP), a
      structural isomer of IF, shows urotoxic but no nephrotoxic side effects. The
      development of haemorrhagic cystitis during therapy with IF or CP can be
      prevented by the uroprotective drug sodium-2-mercaptoethanesulphonate (MESNA).
      However, even in the presence of MESNA, Fanconi syndrome may still develop after
      therapy with IF. Using the renal tubular cell line LLC-PK1, we investigated
      whether there is a protective effect of either MESNA or of its major metabolite
      DIMESNA, in combination with metabolites of IF or CP, on thymidine incorporation,
      uridine incorporation or total protein. DIMESNA, the dimer of MESNA, is the
      dominant form of the molecule in the circulation; the proximal tubular cell must
      convert this back to MESNA at the expense of glutathione, before it can exert its
      uroprotective action. We did not find a protective effect of DIMESNA under any of
      the experimental conditions tested. LLC-PK1 cells exposed to 3 mmol/l DIMESNA did
      not convert DIMESNA to MESNA. The toxic effect of the CP metabolite 4-OOH-CP was
      more pronounced in the presence of DIMESNA than in its absence. MESNA completely
      prevented the toxic effects of acrolein and of 4-OOH-CP. The toxic effects of 4
      OOH-IF and of chloracetaldehyde, two major metabolites of IF, were significantly
      reduced in the presence of MESNA. However, even at 30-fold molar excess of MESNA
      over a 4-OOH_IF, thymidine incorporation remained reduced by 40% compared with
      controls, indicating incomplete protection of tubular cells against metabolites
      of IF. Similarly, the effect of chloracetaldehyde was not completely reversed by
      MESNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524594
TI  - Enhancement of tumor growth by basement membrane: modulation of growth and
      angiogenesis by laminin-derived synthetic peptides.

PMID- 7524599
TI  - Serious pulmonary complications in patients receiving recombinant granulocyte
      colony-stimulating factor during BACOP chemotherapy for aggressive non-Hodgkin's
      lymphoma.
AB  - Four of 12 Chinese patients receiving BACOP, in combination with recombinant
      human granulocyte colony-stimulating factor, for aggressive non-Hodgkin's
      lymphoma developed a rapidly progressive pneumonic illness characterised by
      diffuse pulmonary infiltrates and hypoxaemia. The condition proved fatal in
      three, and in none could an infective cause be identified. A retrospective
      analysis revealed only one episode of pneumonia in the previous 24 patients in
      whom the same BACOP regimen was administered without granulocyte colony
      stimulating factor support. Granulocyte colony-stimulating factor, by augmenting
      white cell production, pulmonary sequestration and margination and production of
      toxic oxygen species, may exacerbate underlying subclinical bleomycin pulmonary
      toxicity. Caution should be exercised before using granulocyte-stimulating
      factors in bleomycin-containing regimens.

PMID- 7524600
TI  - Identification of glioma-associated antigen MUC 2-63 as CD44.
AB  - Monoclonal antibody MUC 2-63 recognises neurogenic tumours and has been used
      successfully for radioimaging human malignant gliomas. We now show that the MUC 2
      63 antigen has the same tissue distribution and molecular weight range as the
      CD44 antigen and confirm the identity of these two molecules in blocking studies
      using MUC 2-63 and the CD44 anti-framework antibody F10-44-2. Thus not only MUC 2
      63 but also other anti-CD44 monoclonal antibodies should prove useful in imaging
      and, perhaps, therapy of brain tumours.

PMID- 7524601
TI  - APC mutation analysis by chemical cleavage of mismatch and a protein truncation
      assay in familial adenomatous polyposis.
AB  - Overall, the causative APC mutation has been identified in only 30% of the
      patients with familial adenomatous polyposis (FAP) who have been included in
      studies reported in the literature. In order to determine the true frequency of
      detectable APC mutations, we set out to search exhaustively the entire coding
      region of APC for causative mutations in ten patients with classical FAP from
      Scottish kindreds shown to be linked to 5q markers. Chemical cleavage of mismatch
      analysis was employed as the initial screening technique. Mutations were
      confirmed by direct DNA sequencing and shown to generate a premature stop codon
      by an in vitro protein synthesis assay. Mutations resulting in a premature stop
      codon either by base substitution or by frameshift were identified in nine
      families. Although the remaining kindred was linked to intragenic APC markers
      with a lodscore of 1.69 at Zmax = 0.0, further analysis of DNA, RNA and
      chromosome spreads from the proband failed to detect any abnormality. This was
      despite employing single-strand conformation polymorphism (SSCP) analysis,
      heteroduplex analysis, DNA sequencing, reverse transcription-polymerase chain
      reaction (RT-PCR) analysis for splicing defects, a protein truncation test
      encompassing the entire APC gene and fluorescent in situ hybridisation chromosome
      analysis (FISH). These data show that 90% of these FAP kindreds had APC mutations
      detectable by chemical cleavage of mismatch and that none of the numerous other
      techniques employed could detect the mutation in the remaining kindred. This
      study shows the value of screening the APC gene using a combination of chemical
      cleavage of mismatch analysis and an in vitro protein truncation test.

PMID- 7524597
TI  - [Portal thrombosis: the diagnostic and therapeutic aspects and clinical cases].
AB  - The authors report their experience, from 1983 to 1992, in the treatment of
      portal vein thrombosis and discuss various aetiological factor of obstruction
      also underlining the frequent and important association with portal hypertension.
      The authors emphasize the crucial role of the modern diagnostic techniques such
      as endoscopy and imaging radiology (U.S., C.T., angiography). Although these
      techniques not always allow a conclusive evidence in relation to aetiology,
      however, it is possible to have a rationale for the treatment, i.e. medical,
      sclerotherapeutic or surgical. As related to the surgical procedures, the authors
      -based on their personal experience--believe the best are the non-derivative
      ones.

PMID- 7524602
TI  - Human colon cancer cell lines show a diverse pattern of nitric oxide synthase
      gene expression and nitric oxide generation.
AB  - A panel of human colonic adenocarcinoma cell lines was examined both for
      expression of mRNAs of the nitric oxide synthase (NOS) gene family and for
      evidence of enzymic activity based on citrulline and nitrite (NO2-) formation.
      Reverse transcription-polymerase chain reaction (RT-PCR), revealed that all lines
      (SW480, SW620, DLD-1 and WiDr) expressed mRNA for the Ca(2+)-dependent
      endothelial (e)NOS, while SW480 cells also expressed the Ca(2+)-dependent
      neuronal (n)NOS. The mRNA for the Ca(2+)-independent inducible (i)NOS was
      expressed both by cytokine-stimulated and by unstimulated SW480, SW620 and DLD-1
      cells, but none was seen at any time in the WiDr cells. There was, however,
      little correlation between mRNA expression and enzymic activity based on
      citrulline and NO2- formation. Thus none of the cell lines exhibited measurable
      Ca(2+)-dependent NOS activity, while Ca(2+)-independent NOS activity was seen in
      all but the WiDr cells. Furthermore, DLD-1 cells generated citrulline with
      resultant NO2- formation only after stimulation with lipopolysaccharide (LPS)
      and/or cytokines, while SW480 and SW620 did so constitutively. Thus RT-PCR
      studies indicate that tumour cells of similar epithelial origin display a diverse
      pattern of NOS gene family expression, and parallel biochemical studies clearly
      indicate that such expression does not always result in measurable enzymic
      activity leading to the generation of NO.

PMID- 7524603
TI  - Calcium-dependent photodynamic action of di- and tetrasulphonated aluminium
      phthalocyanine on normal and tumour-derived rat pancreatic exocrine cells.
AB  - Important differences exist in the responses to photodynamic agents of normal and
      tumour-derived pancreatic acinar cells. In the present study amylase release has
      been used to assess the mechanisms by which the photodynamic drugs tetra- and
      disulphonated aluminium phthalocyanine (A1PcS4, A1PcS2) act on pancreatic cells
      via energy and calcium-dependent activation and transduction pathways. The
      photodynamic release of amylase was found to be energy dependent and inhibited by
      the chelation of free cytoplasmic calcium but not by the removal of extracellular
      calcium. In contrast to their effects on normal acinar cells, the photodynamic
      action of A1PcS4 and A1PcS2 was to inhibit amylase secretion from pancreatoma AR4
      2J cells. Removal of extracellular calcium reversed this inhibitory effect on AR4
      2J cells and produced a significant increase in amylase release, but chelation of
      free cytoplasmic calcium did not affect the inhibitory photodynamic action of the
      phthalocyanines on amylase release from the tumour cells. Overall, these results
      demonstrate further important distinctions between the photodynamic action of
      sulphonated aluminium phthalocyanines on normal versus tumour exocrine cells of
      the pancreas and indicate that calcium plays an important role in photodynamic
      drug action, since these agents affected intracellular calcium mobilisation at
      some distal point in the membrane signal transduction pathway for regulated
      secretion. Furthermore, the photodynamic inhibition of constitutive secretion in
      tumour cells may involve a calcium-dependent membrane target site or modulation
      of membrane calcium channels by activation of protein kinase C.

PMID- 7524604
TI  - Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of
      clinical and molecular data.
AB  - Ewing tumours (ET), including Ewing's sarcoma and peripheral primitive
      neuroectodermal tumour, are well characterised at the molecular level by a unique
      chromosomal rearrangement which fuses the EWS gene to one of two closely related
      ETS proto-oncogenes, FLI-1 or ERG. Expression of the resulting chimaeric
      transcripts can be readily detected by reversed transcriptase polymerase chain
      reaction (RT-PCR). This approach led to the identification of a number of
      different exon combinations at the junction site of coding sequences. The
      physiological consequences of the observed variability in the hinge region of EWS
      chimaeric proteins are not known. We have analysed tumour-derived material from
      30 ET patients with well-documented clinical course (18 with localised and 12
      with metastatic disease at diagnosis) for the presence of EWS/FLI-1 or EWS/ERG
      RNA. Karyotypes were obtained in 21 out of 27 cases and analysed by routine
      cytogenetics. A chromosome 22 rearrangement was demonstrated in 18 cases (67%).
      In contrast, RT-PCR revealed the presence of chimaeric transcripts in 28 tumours
      (93%), with fusions of EWS exon 7 to FLI-1 exons 6 (19/28), 5 (4/28) and 7
      (1/28). In addition, EWS/FLI-1 exon combinations 10/5 and 9/4 were observed in
      one case each. In the last tumour, the presence of at least four additional
      splicing variants corresponding to fusion of EWS exon 7 to FLI-1 exons 4, 6, 8
      and 9 was demonstrated. Two tumours expressed EWS/ERG fusion transcripts
      involving EWS exon 7 and ERG exon 6. In this study, EWS/FLI-1 exon combinations
      7/6 (type I) predominated over 7/5 (type II) in localised ET (14 versus 1) and
      were more abundant in tumours affecting the long bones (9 versus 0), whereas in
      central axis tumours and metastatic disease there was only little difference in
      the frequency of the two types. So far, no correlations between different
      chimaeric EWS transcripts and any other clinical parameters have been identified.

PMID- 7524605
TI  - Filgrastim fails to improve haemopoietic reconstitution following myeloablative
      chemotherapy and peripheral blood stem cell rescue.
AB  - The morbidity of high-dose chemotherapy has been considerably reduced by the use
      of autologous peripheral blood progenitor cell reinfusion. Most studies have used
      myeloid colony-stimulating factors after stem cell reinfusion, making it
      difficult to determine the relative contribution of each of these variables to
      the early recovery of blood cells. The financial implications of colony
      stimulating factor use are an area of concern as dose intensification in
      chemosensitive malignancies is increasingly employed. We have studied 19
      consecutive patients receiving high-dose chemotherapy with and without filgrastim
      (Amgen, granulocyte colony-stimulating factor, G-CSF) after stem cell infusion to
      examine its effect on the kinetics of blood cell recovery, the complications of
      myelosuppression and the associated costs. Analysis of the two treatment groups
      reveals that administration of filgrastim 10 micrograms kg-1 day-1 following stem
      cell reinfusion does not further accelerate haemopoietic recovery, fails to
      reduce the incidence of neutropenic fever or antibiotic usage and significantly
      increases the cost of the procedure. The results of this study do not support the
      routine use of filgrastim after high-dose chemotherapy and peripheral blood stem
      cell reinfusion.

PMID- 7524608
TI  - The epitope for anti-type VII collagen monoclonal antibody (LH7:2) locates at the
      central region of the N-terminal non-collagenous domain of type VII collagen.
AB  - The monoclonal antibody LH7:2, which recognizes type VII collagen, is now used in
      the diagnosis and prenatal diagnosis of epidermolysis bullosa dystrophica. We
      constructed the expression vector which contains the cDNA fragment of type VII
      collagen. Western blot with LH7:2 was carried out with the resultant fusion
      proteins which overlap each other, and we found that reactivity is located in the
      central region of the N-terminal non-collagenous domain of type VII collagen, at
      a position 81 kDa upstream from the collagenous domain. This epitope mapping for
      LH7:2 may be useful in studying the role of type VII collagen in epidermolysis
      bullosa dystrophica.

PMID- 7524607
TI  - Phase I study of mitozantrone, methotrexate and mitomycin with granulocyte colony
      stimulating factor (filgrastim) in patients with advanced breast cancer.
AB  - The combination of mitozantrone, methotrexate and mitomycin (3M) gives a response
      rate of around 50% in patients with advanced breast cancer. The predominant
      toxicity is haematological. In this study, previously untreated patients were
      given 3M with increasing doses of mitozantrone (7-14 mg m-2) with recombinant
      human granulocyte colony-stimulating factor (metHuG-CSF) (filgrastim) to prevent
      marrow toxicity. Doses administered were 7 mg m-2 mitomycin i.v. 6 weekly,
      methotrexate i.v. 35 mg m-2 (maximum 50 mg) 3 weekly and mitozantrone i.v. 3
      weekly as follows: 7 mg m-2, six patients (group 1); 10 mg m-2, six patients
      (group 2); 12 mg m-2, six patients (group 3); 14 mg m-2, six patients (group 4);
      all on day 1 for six cycles at the assigned dose. All patients received
      filgrastim (Amgen 0.3 mg ml-1) at a dose of 5 micrograms kg-1 subcutaneously
      daily on days 4-17 of each cycle. All treatment was given on an out-patient
      basis. A total of 24 patients were entered into the study. The median age was 63
      years (range 48-75). ECOG performance status was 0 in ten, 1 in 11 patients and 2
      in three patients. Locoregional disease alone was present in seven patients. The
      remainder had one or more sites of metastases. The actual dose administered to
      the 24 patients was as follows. The six patients in group 1 all completed six
      courses of treatment as per protocol. In group 2, three patients completed six
      courses, two stopped because of toxicity after one and four courses and one had
      progressive disease after one course. In group 3, three patients completed and
      three stopped early because of progressive disease. In group 4, two patients
      completed, one progressed after four courses and three responding patients
      stopped treatment because of toxicity. The maximum tolerated dose of mitozantrone
      in the 3M combination was 12 mg m-2. The use of filgrastim with increasing doses
      of chemotherapy prevents neutropenia, but other toxicities, namely
      thrombocytopenia and lethargy, then become dose limiting.

PMID- 7524609
TI  - The basement membrane zone of the nail.
AB  - The anatomy of the epidermis, dermis and subcutaneous tissues of the nail
      apparatus is distinct from that of non-appendageal skin. Apart from the
      demonstration of the longitudinal configuration of the dermal-epidermal junction
      of the nail bed, there have been no studies of the composition of the basement
      membrane zone of the nail apparatus. We obtained three human accessory digits,
      including one thumb, all of which had been amputated for cosmetic reasons, and
      were without known pathology. Specimens were stained with a battery of monoclonal
      and polyclonal antibodies which target normal basement membrane zone antigens,
      and studied by indirect immunofluorescence. This study demonstrated that the four
      distinct regions of the nail, namely the proximal nail fold, the nail matrix, the
      nail bed and the hyponychium expressed all the target antigens found in the
      normal non-appendageal basement membrane. In particular, there was normal
      expression of the epidermal-associated antigens, the 220- and 180-kDa bullous
      pemphigoid antigens, and the alpha 6 beta 4 integrin. There was also normal
      expression of the lamina lucida antigens LH39, GB3 and laminin. It is of interest
      that the dermal-associated components, namely the 285-kDa linear IgA antigen, the
      extracellular matrix glycoproteins chondroitin sulphate, type VII collagen and
      its closely associated proteins, and the poorly characterized antigen for LH24
      and LH39 were all normally expressed. Fibronectin, which is not a normal basement
      membrane zone component, was diffusely expressed in the extracellular matrix, but
      did not accentuate the basement membrane zone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524610
TI  - Immunohistochemical localization of cytokeratins and involucrin in calcifying
      epithelioma: comparative studies with normal skin.
AB  - The expression of cytokeratins and involucrin varies greatly in different
      epithelia, and this raises the possibility that detailed analysis of these
      epidermal proteins might provide a means of identifying various skin tumours. The
      present study was conducted to determine the immunohistochemical distribution of
      cytokeratins and involucrin in calcifying epithelioma of Malherbe, in order to
      elucidate the nature and differentiation of this tumour. To correlate the
      immunohistochemical profile with the most frequent histological patterns, we
      categorized the basophilic, transitional, shadow, and squamoid cells, and the
      shreds of keratin. Comparative studies with normal skin showed that the shadow
      and transitional cells corresponded to hair cortex cells, the squamoid cells to
      the outer root sheath, the basophilic cells adjacent to the stroma to the
      outermost cell layer of the outer root sheath between the lower permanent portion
      and upper transient portion of the follicles, and the basophilic cells adjacent
      to the transitional cells to the hair matrix. The expression of cytokeratins in
      most shreds of keratin was similar to that in squamoid cells. Calcifying
      epithelioma was, therefore, shown to be composed of tumour cells differentiating
      into both the hair cortex and outer root sheath. These tumour cells were
      differentiated from basophilic cells, which showed the same staining patterns as
      the outermost cell layer of the outer root sheath between the lower permanent
      portion and upper transient portion of the hair follicles, supporting the
      hypothesis that the keratinocytes in the outermost cell layer can differentiate
      into the transitional portion of the follicle and anagen hair.

PMID- 7524606
TI  - Sequential resection of residual abdominal and thoracic masses after chemotherapy
      for metastatic non-seminomatous germ cell tumours.
AB  - Thirty-eight patients with advanced non-seminomatous germ cell tumours (NSGCTs)
      underwent multiple surgical interventions (two in 33 patients, three in four
      patients, four in one patient) after cisplatin-based chemotherapy. All patients
      had normal serum tumour markers but persistent radiographic masses. The larger
      mass was routinely resected first. Fifteen patients (39%) had dissimilar
      histological findings at sequential surgical procedures, 12 of whom demonstrated
      less favourable pathological features during the first operation and three at the
      second. Patients who underwent both retroperitoneal lymph node dissection (RPLND)
      and lung resection showed less favourable histological features in the
      retroperitoneum in nine cases and in the lung in three cases. Eight of 16
      patients (50%) without mature teratoma in their primary tumours showed complete
      necrosis/fibrosis at all surgical interventions, whereas all patients whose
      primary tumour was classified as malignant teratoma intermediate demonstrated
      mature teratoma at least at one anatomical site. As histology of post
      chemotherapy residual masses cannot be extrapolated from one anatomical site to
      another, patients usually are properly managed by excision of all residual
      masses. In particular, in patients with necrosis/fibrosis at lung resection
      omission of RPLND is not advised.

PMID- 7524612
TI  - Alpha-2-macroglobulin as the major defence in acute pseudomonal septic shock in
      the guinea-pig model.
AB  - An intravenous injection of 1.2 mg/kg of Pseudomonas aeruginosa elastase induces
      immediate lethal shock in guinea-pigs. In the present study, alpha-2
      macroglobulin (alpha 2M) was shown to be the major factor in guinea-pig plasma
      that inhibits the enzymatic activity of elastase in vitro. Depletion of
      circulating alpha 2M by injecting anti-guinea-pig alpha 2M rabbit IgG F(ab')2
      rendered the animals sensitive to a dose of elastase of 0.05 mg/kg. When the
      alpha 2M-depleted guinea-pigs were reconstituted with human alpha 2M, this
      sensitivity was reversed. Lethal shock did not occur in alpha 2M-depleted animals
      even at an elastase dose of 0.2 mg/kg when Hageman factor was simultaneously
      depleted, indicating that elastase induces shock through activation of the
      Hageman factor-dependent system. Similar results were obtained when the culture
      supernatants of an elastase-producing strain, IFO-3455, were used instead of the
      purified elastase, whereas no cardiovascular changes occurred, even in the alpha
      2M-depleted guinea-pigs, when the culture supernatants were pretreated with an
      elastase specific inhibitor (zincov) or when the culture supernatants of an
      elastase non-producing strain, PA-103 were used.

PMID- 7524611
TI  - Angiogenesis and reinnervation in skin flaps: the effects of ischaemia examined
      in an animal model.
AB  - In clinical flap transplantation, ischaemia may alter reinnervation patterns
      either directly or by affecting angiogenesis. This study presents the effects of
      ischaemia on innervation in totally denervated, transiently (30 minutes) or
      prolongedly ischaemic skin flaps studied immunohistochemically with antisera to
      PGP 9.5, CGRP and VWF. Following transient ischaemia, an increase in PGP
      immunoreactive (PGP-IR) and CGRP-IR nerve fibres in distant skin by day 12 was
      followed by increased innervation in immediately adjacent skin. The latter
      increase was maintained up to 24 days which allowed near normal innervation at
      the suture margin and in adjacent flap tissue, 0.5 cm from the margin. There was
      concomitant reinnervation from the pedicle by day 24. In prolongedly ischaemic
      flaps, an earlier and more prolonged increase in innervation was seen in the
      entire surrounding skin, with innervation around the suture line at 24 days
      resembling that in the transiently ischaemic flaps despite initial complete nerve
      fibre depletion in this area. Hypertrophic nerve fibre clusters were seen in
      fibrotic areas overlying the pedicle. Vascular changes were similar in both
      groups with vascularization preceding reinnervation. There were no significant
      differences in reinnervation between the transiently and prolongedly ischaemic
      flaps at 24 days, despite considerable initial variations. Ischaemia, CGRP,
      mediators of chronic inflammation and epidermal factors appeared to stimulate
      angiogenesis and reinnervation.

PMID- 7524613
TI  - Fine epitope mapping of monoclonal antibodies to the NH2-terminal part of von
      Willebrand factor (vWF) by using recombinant and synthetic peptides: interest for
      the localization of the factor VIII binding domain.
AB  - Two different approaches were used in order to define the epitope of three
      monoclonal antibodies (MoAbs) against the NH2-terminal part of the mature subunit
      of von Willebrand factor (vWF) which contains its factor VIII (FVIII) binding
      site. First, a vWF cDNA fragment library using the bacteriophage lambda gt11
      expression vector was screened with radiolabelled MoAbs. The epitope of each MoAb
      was defined, following sequence analysis, by the overlapping DNA sequence of
      immunoreactive clones. MoAb 32B12, a potent inhibitor of FVIII/vWF interaction,
      binds within the Glu35-Ile81 sequence of vWF subunit. MoAb 14A12, a non
      inhibitory antibody, recognizes a sequence within Thr141-Val220. MoAb 31H3, a
      partial inhibitory antibody, gives no positive clone. In the second method, a
      panel of 24 synthetic pentadecapeptides corresponding to the first NH2-terminal
      105 amino acid residues was used to block the binding of inhibitor MoAbs to
      immobilized vWF in an ELISA system. The localization of MoAb 32B12 epitope was
      confirmed and restricted to the Met51-Ala60 sequence. The MoAb 31H3 binding to
      vWF is inhibited by two synthetic peptides with the overlapping sequence Cys66
      Gly76. All these data confirm that the FVIII binding site of vWF is not limited
      to the binding area (Thr78-Thr96) of the previously described MoAbs inhibiting
      FVIII/vWF interaction but is composed of several key sequences.

PMID- 7524614
TI  - Immunochemical estimation of haemoglobin types in red blood cells by FACS
      analysis.
AB  - A fixation and permeabilization procedure using formaldehyde and acetone has been
      developed which allows immunostaining of intracellular haemoglobin for
      fluorescence activated cell sorter (FACS) analysis of erythrocytes. The treatment
      preserves antigenicity and light-scattering properties. Validation of the method
      was given by the correlation of F cell number in adults determined by FACS
      analysis with that assessed by microscopic examination of cell smears, and by the
      direct relationship between beta chain synthesis and intensity of beta chain/Hb A
      immunofluorescence within fetal erythrocyte samples known to vary in their beta
      chain/Hb A content. The procedure is rapid, non-subjective and sensitive, and
      makes analysis of haemoglobin content, type and distribution amongst red cell
      populations possible.

PMID- 7524615
TI  - Rolling and stationary cytoadhesion of red blood cells parasitized by Plasmodium
      falciparum: separate roles for ICAM-1, CD36 and thrombospondin.
AB  - Adhesion of parasitized erythrocytes to microvascular endothelium is a central
      event in the pathogenesis of severe falciparum malaria. We have characterized the
      adhesion of flowing parasitized red blood cells to three of the known endothelial
      receptors coated on plastic surfaces (CD36, intercellular adhesion molecule-1
      (ICAM-1) and thrombospondin (TSP)), and also to cells bearing these receptors
      (human umbilical vein endothelial cells (HUVEC) and platelets). All of the
      surfaces could mediate adhesion at wall shear stress within the physiological
      range. The great majority of adherent parasitized cells formed rolling rather
      than static attachments to HUVEC and ICAM-1, whereas static attachments
      predominated for platelets, CD36 and TSP. Studies with monoclonal antibodies
      verified that binding the HUVEC was mainly via ICAM-1, and to platelets via CD36.
      Adhesion via ICAM-1 was least sensitive to increasing wall shear stress, but
      absolute efficiency of adhesion was greatest for CD36, followed by ICAM-1, and
      least for TSP. TSP did not give long-lasting adhesion under flow, whereas cells
      remained adherent to CD36 or ICAM-1. We propose that the different receptors may
      have complementary roles in modulating adhesion in microvessels. Initial
      interaction at high wall shear stress may be of a rolling type, mediated by ICAM
      1 or other receptors, with immobilization and stabilization occurring via CD36
      and/or TSP.

PMID- 7524616
TI  - Establishment of a human T-cell line with deficient surface expression of
      glycosylphosphatidylinositol (GPI)-anchored proteins from a patient with
      paroxysmal nocturnal haemoglobinuria.
AB  - A novel interleukin-2 dependent T-cell line, PMT-2Y, was established from the
      peripheral blood of a patient with paroxysmal nocturnal haemoglobinuria (PNH) by
      human T lymphotropic virus type I (HTLV-I)-mediated transformation. PMT-2Y cells
      are positive for CD2, CD3, CD4, CD25, T cell receptor alpha beta and HLA-DR, but
      negative for CD1, CD7, CD8, CD19 and CD20, indicating that the clone belongs to a
      helper/inducer subset of T cells. PMT-2Y cells have the monoclonal integration of
      HTLV-I proviral DNA, suggesting that they derived from a single clone. Moreover,
      they lack surface expression of complement regulatory proteins such as DAF (CD55)
      and CD59, that are the most important glycosylphosphatidylinositol (GPI)-anchored
      membrane proteins defective in haemopoietic cells of patients with PNH. Northern
      blot analysis, however, revealed the production of normal levels of DAF mRNAs.
      Thus, PMT-2Y is derived from a PNH T cell clone and may be a useful model to
      study PNH.

PMID- 7524617
TI  - Altered surface marker expression and function of G-CSF-induced neutrophils from
      test subjects and patients under chemotherapy.
AB  - We have previously reported an altered surface marker expression and chemotaxis
      of G-CSF-induced neutrophils from patients with severe congenital neutropenia.
      However, effects of G-CSF and influence of the underlying disease on neutrophils
      could not be discerned. In this study we have evaluated the effects of G-CSF on
      neutrophil phenotype and function in patients under chemotherapy and in healthy
      test subjects. We found a significantly enhanced expression of Fc gamma RI, CD14
      and CD54 and a decrease in the level of Fc gamma RIII during G-CSF treatment. In
      addition, motility of G-CSF-induced neutrophils was significantly decreased. The
      effects were seen in patients under cytotoxic chemotherapy and in healthy test
      subjects. Surface marker alterations and neutrophil motility were affected by G
      CSF administration in a dose-dependent manner. Kinetic studies on neutrophils
      from healthy test subjects demonstrated that all effects could be seen after a
      single administration of 300 micrograms G-CSF and began to appear within 4 h.
      Release of partially immature neutrophils from the bone marrow and indirect
      activation of these cells by G-CSF are discussed as possible reasons for the
      findings presented. They demonstrate that G-CSF has profound effects on
      neutrophil phenotype and function in vivo which might have clinical implications.

PMID- 7524618
TI  - Late-appearing Philadelphia chromosome in a patient with acute nonlymphocytic
      leukaemia derived from myelodysplastic syndrome: detection of P210- and P190-type
      bcr/abl fusion gene transcripts at the leukaemic stage.
AB  - We describe a patient with acute nonlymphocytic leukaemia (ANLL) derived from
      myelodysplastic syndrome in whom the Philadelphia chromosome (Ph1) first emerged
      at the late stage of ANLL transformation. Cytogenetically, the Ph1 chromosome was
      not detected until the late stage of ANLL transformation, 14 months after the
      transformation following a 3-month history of refractory anaemia with excess of
      blasts. The cells with and without the Ph1 chromosome had a common abnormal
      chromosome, t(3;3) (q21;q26). The reverse transcription-polymerase chain reaction
      analysis showed no bcr/abl message at diagnosis. However, the mRNA encoding
      P210bcr/abl was detected in the early stage of ANLL transformation. Furthermore,
      the mRNAs encoding both P210bcr/abl and P190bcr/abl were detected in the late
      stage of ANLL transformation when the Ph1 chromosome was detected by cytogenetic
      analysis. These evidences support a multistep pathogenesis of leukaemias, and the
      products of bcr/abl fusion gene may influence the course of disease.

PMID- 7524619
TI  - Ex vivo expansion and selection of retrovirally transduced bone marrow: an
      efficient methodology for gene-transfer to murine lympho-haemopoietic stem cells.
AB  - An efficient procedure for the insertion of genetic markers into a large
      proportion of the mouse haemopoietic system was developed, based on the in vitro
      expansion of retrovirally infected bone marrow and selection of the transduced
      cells. Bone marrow cells harvested 4 d after 5-FU treatment were incubated under
      IL-3/SCF stimulation and their growth dynamic, susceptibility to retroviral
      infection and reconstitution capacity evaluated throughout the incubation period.
      On the third day of culture a maximum expansion in the CFU-GM and CFU-S12
      progenitor pools was observed (130- and 15-fold, respectively), with no apparent
      impairment in long-term repopulating precursors. This expansion was, however,
      accompanied by a net decrease in the CFU-GM susceptibility to the infection by
      supernatants containing a Moloney-derived ecotropic retroviral vector carrying
      the neor gene. The designed protocol thus involved the infection of freshly
      harvested 5-FU-treated bone marrow, followed by expansion under IL-3/SCF
      stimulation and selection for resistance to G418. This procedure allowed us to
      harvest up to 780 CFU-GM and 50 CFU-S12 per 10(5) bone marrow cells, free from
      non-genetically marked progenitors. Most of the animals reconstituted with the
      transduced marrow bore, for at least 5 months, a very high proportion of bone
      marrow, spleen and thymus cells tagged with the reporter gene. These results,
      together with the high percentage of haemopoietic precursors bearing the neor
      gene and expressing resistance to G418 5 months after the transplantation
      indicates that long-term lympho-haemopoietic repopulating cells were efficiently
      transduced and selected in vitro under conditions that preserve their self
      renewal and differentiation properties. This gene-transfer methodology may
      improve the development of gene therapy protocols where the purging of non
      transduced precursors would guarantee a lasting and uniform expression of
      exogenous genes.

PMID- 7524621
TI  - Phenotypic and functional analysis of bone marrow progenitor cell compartment in
      bone marrow failure.
AB  - Many laboratory findings have demonstrated that the haemopoietic stem cell
      compartment is defective in aplastic anaemia (AA). AA bone marrow (BM) and
      peripheral blood (PB) are profoundly deficient in colony-forming cells, and AA
      progenitors fail to proliferate in long-term assays even in the presence of an
      intact stroma. Our study was designed to characterize some quantitative and
      qualitative aspects of the progenitor cell defect in AA. Using flow cytometric
      analysis of BM from new AA patients and from those recovering after
      immunosuppressive therapy, we determined that the numbers of CD34+ and CD33+
      cells were markedly decreased in AA. Although PB neutrophil counts did not
      correlate with BM CD34+ cell numbers in acute disease, there was an association
      between the overall severity of the disease and the degree of CD34+ cell
      reduction. A decrease in BM CD33+ cells was a common finding in MDS patients, but
      reduction in CD34+ cells was found only in some hypoplastic MDS cases. Sorting
      experiments demonstrated lower plating efficiency for purified CD34+ cells from
      AA BM in comparison to controls. Thus, diminished colony formation of total BM
      appeared to result from both quantitative and qualitative defects. Based on the
      association between increased cycling and c-kit receptor expression on CD34+
      cells, we found that the mitotically active CD34+ cells bearing the c-kit antigen
      were reduced in AA. With clinical improvement, CD34+ and CD33+ cells increased in
      correlation with PB parameters, but they did not return to normal values. Sorted
      CD34+ cells from recovered patents showed improved plating efficiency.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7524620
TI  - Inactivation of the retinoblastoma gene appears to be very uncommon in
      myelodysplastic syndromes.
AB  - Rearrangements of the retinoblastoma (RB) gene have been reported in a few cases
      of myelodysplastic syndromes (MDS). In addition, low or absent expression of the
      RB protein is found in 20-30% of cases of acute myeloid leukaemias (AML),
      particularly in AML with a monocytic component (M4 or M5). We performed Southern
      blot analysis of the RB gene in 90 cases of MDS, including 37 cases of chronic
      myelomonocytic leukaemia (CMML). None of them had progressed to AML at the time
      of study. In 37/90 patients (including 20 CMML) Northern blot analysis, study of
      RB protein by immunocytochemistry on bone marrow slides, and detection of point
      mutations in exons 20-24 of the RB gene was also made, using single strand
      conformation polymorphism analysis (SSCP). No abnormal Southern profile was found
      in any of the 90 patients. Northern blot and immunocytochemical study of RB
      protein were normal in the 37 cases studied. SSCP analysis detected a point
      mutation in 2/37 patients tested. Direct sequencing confirmed the mutation in
      each case, which involved intron 21 and intron 23, respectively, and was located
      outside splicing sites of the neighbouring exons. These findings suggest that
      abnormalities of the RB gene and its expression must be very rare in MDS, and
      play a minor role, if any, in the pathophysiology of those disorders, at least
      before progression to AML.

PMID- 7524622
TI  - Postnatal changes of CD45 expression in peripheral blood T and B cells.
AB  - One known postnatal change of CD45 expression is the decline of the CD45RAhigh
      CD45ROlow T subsets and the reciprocal increase of the CD45RAlow CD45ROhigh T
      subsets in the peripheral blood. Using a panel of monoclonal antibodies reactive
      with either protein or carbohydrate epitopes on the variable regions of CD45, we
      were able to detect more postnatal changes of CD45 expression. These changes are
      largely caused by modulation of the CD45 glycosylation, including: (1) lesser
      sialylation of the CD45RA region on T cells, and (2) differential sialylation of
      the CD45RB region leading to the distinction of CD45RBhigh and CD45RBlow T and B
      subsets. In addition, the existence of the CD45RAdim CD45ROdim labelled as
      transitional T cells is only found during the postnatal life. These changes may
      reflect the maturation of the immune system.

PMID- 7524624
TI  - Age-related alterations in erythroid and granulopoietic progenitors in Diamond
      Blackfan anaemia.
AB  - Mechanisms involved in the erythroid failure characterizing Diamond-Blackfan
      anaemia (DBA) remain unidentified. The general consensus is that the defect is
      intrinsic to the marrow erythroid progenitor, but the target progenitor cell has
      not been precisely identified, and in vitro studies have revealed considerable
      heterogeneity between patients. In order to understand better the meaning of such
      a biological heterogeneity, we examined the in vitro response of erythroid
      progenitors CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit
      erythroid) to erythropoietin (Epo), interleukin-3 (IL-3) and stem cell factor
      (SCF) in a large series of 24 patients from 1 month to over 20 years of age.
      Results of colony assays revealed a striking correlation between the age of the
      patient and the extent of the abnormalities detected in vitro. Therefore, despite
      profound anaemia, 80% (7/10) of the patients studied within 1 year of diagnosis
      had normal numbers of both CFU-E and BFU-E which exhibited a normal response to
      cytokines. In contrast, 12/14 patients followed up for more than 3 years had
      decreased numbers of erythroid progenitors, in seven cases associated with
      decreased colony-forming unit granulocyte-macrophage (CFU-GM). The number of CFU
      E and BFU-E was not normalized even by the addition of high concentrations of
      combined Epo, IL-3 and SCF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524625
TI  - Response of T-beta CD8+ lymphocytosis-associated neutropenia to G-CSF.
AB  - Only limited data are reported on the response to granulocyte-colony stimulating
      factor (G-CSF) of large granular lymphocytosis-associated neutropenia. We report
      features of such a case who developed a suppurating leg ulcer following a dog
      bite. G-CSF was used to increase the neutrophil count, allowing the ulcer to be
      successfully skin grafted.

PMID- 7524623
TI  - The relative levels of beta A and beta S mRNAs in Hb S heterozygotes and in
      patients with Hb S-beta(+)-thalassaemia or Hb S-beta(+)-HPFH combinations.
AB  - We have used a quantitative reverse transcription/polymerase chain reaction
      (RT/PCR) procedure to evaluate the relative amounts of beta A and beta S mRNA
      transcripts in eight subjects with a simple Hb S heterozygosity, in six with Hb S
      beta(+)-thalassaemia (thal), and in three individuals with Hb S-beta(+)-HPFH
      [hereditary persistence of fetal haemoglobin (Hb)] [two with the Atlanta type and
      one with the G gamma-202 (C-->G) substitution]. A balanced synthesis of beta A
      and beta S mRNAs was observed in all Hb S heterozygotes, whereas the beta A mRNA
      levels were reduced to approximately 16% of that of the beta S mRNA in the six Hb
      S-beta(+)-thal compound heterozygotes, to approximately 43% in the two subjects
      with Hb S-beta(+)-HPFH (Atlanta type), and to 23.8% in the one individual with Hb
      S-beta(+)-HPFH [G gamma-202 (C-->G) substitution]. The higher Hb A versus Hb S
      levels observed in all groups of the patients studied, further confirm a post
      translational control mechanism in determining the levels of Hb A and Hb S in the
      peripheral blood of these individuals. The procedure described here provides an
      accurate and easy method for studying the relative expression of particular
      globin genes at the transcriptional level in patients with various
      haemoglobinopathies.

PMID- 7524626
TI  - Cloning and developmental expression of LFB3/HNF1 beta transcription factor in
      Xenopus laevis.
AB  - We have cloned the Xenopus laevis homologue of the LFB3/HNF1 beta transcription
      factor. RNase protection and in situ hybridisation experiments show that XLFB3
      transcription starts in the gastrulating endoderm at stage 10.5 (mid-gastrula).
      At later stages, XLFB3 transcripts within the endoderm are restricted to mid- and
      hindgut and to their derivative organs and tissues. XLFB3 is also expressed in
      the neuroectoderm and in the pronephros anlage. XLFB3 is not expressed in the
      rostral part of all three germ layers, with coincident anterior borders that are
      shifted anteriorly by treatment of developing embryos with retinoic acid. XLFB3
      is a useful marker of early endoderm differentiation and its expression pattern
      along the antero-posterior axis, as well as the response to retinoic acid
      treatment, suggests a role in early morphogenesis.

PMID- 7524628
TI  - Susceptibility of C5b-9(m) to postmortem changes.
AB  - C5b-9(m) is a specific and sensitive marker for myocardial cell necrosis. The
      diagnostic value of this marker would be considerably limited in forensic
      practice if its immuno-histochemical demonstration were hampered by putrefaction
      or autolysis. We could demonstrate C5b-9(m) immunohistochemically in necrotic
      myocardium due to infarction up to the 11th day of experimentally induced
      putrefaction and autolysis, when reliable demonstration of myocardial infarction
      with hematoxylin-eosin was no longer possible. Under the experimental conditions
      of this study, no false positive immunohistochemical staining occurred.

PMID- 7524629
TI  - The value of the Lugol's iodine staining technique for the identification of
      vaginal epithelial cells.
AB  - This paper reports on the specificity of the Lugol's iodine staining technique
      for the detection of vaginal epithelial cells on penile swabs. Air-dried swabs
      taken from the glans of the penis of 153 hospital patients and from 50 healthy
      volunteers, whose last sexual intercourse had taken place at least 5 days
      previously, were stained with Lugol's solution. Glycogenated cells were found in
      more than 50% of the cases studied, even in healthy volunteers without
      urethritis. In almost all of these cases the smear contained at least a few
      polygonal nucleated epithelial cells showing an unequivocal positive Lugol
      reaction. These cells cannot be distinguished from superficial or intermediate
      vaginal cells, by cytomorphology or staining. Urinary tract infections had no
      influence on the glycogen content of male squamous epithelial cells. On the basis
      of these results the Lugol's method can no longer be assumed to prove the
      presence of vaginal cells in penile swabs.

PMID- 7524630
TI  - Activation of the galectin-1 (L-14-I) gene from nonexpressing differentiated
      cells by fusion with undifferentiated and tumorigenic cells.
AB  - Expression of the galectin-1 (L-14-I) gene, elevated in most differentiated and
      transformed cell lines, has been studied in cell hybrid systems. Fusion of L-14-I
      nonproducing rat liver differentiated FAO cells with dedifferentiated rat liver
      BRL3A cells leads to extinction of liver-specific gene expression while L-14-I
      mRNA levels remain high. Interspecific hybrids produced by fusion of tumorigenic
      human osteosarcoma 143TK- with FAO cells show loss of both differentiated
      functions and tumorigenic phenotype and activation of the FAO L-14-I alleles.
      Increased expression of rat L-14-I alleles was also observed in human
      osteosarcoma x rat thyroid cells transient heterokaryons. The data presented here
      show that expression of the L-14-I gene is subject to dominant positive control
      and that it correlates with loss of differentiation-specific functions, but it is
      independent from tumorigenicity. L-14-I activation in FAO cells is achieved by
      treatment with 5-azacytidine. This result suggests that DNA demethylation is
      responsible or a prerequisite for L-14-I activation in hybrids.

PMID- 7524631
TI  - Increased expression of the M(r) 27,000 heat shock protein (hsp27) in in vitro
      differentiated normal human keratinocytes.
AB  - The M(r) 27,000 heat shock protein (hsp27) is a member of the small heat shock
      protein family. Cell differentiation is a process in which a role for small heat
      shock proteins has been suggested. The ability to control the state of
      differentiation in normal human keratinocytes by modification of extracellular
      calcium concentration makes it an ideal in vitro system for exploration of the
      specific components and steps in differentiation. We have focused on the in vitro
      expression of hsp27 in undifferentiated and differentiated human normal
      keratinocytes (HNK) as a marker for differentiation. Immunological methods
      (immunohistochemistry and immunoblotting) as well as Northern blotting were used.
      Cells of the breast cancer line MCF-7 served as a positive control. We
      demonstrated that hsp27 was expressed at low levels in normal human
      keratinocytes, kept under calcium concentrations where cells formed discrete
      colonies of undifferentiated, noncornified cuboidal cells (0.03 mM Ca2+), and
      linked cuboidal cells with a noncornified appearance (0.15 mM Ca2+). Upon
      cultivation in high calcium (1.00 mM Ca2+) where a more morphological state of
      differentiation was reached, more spindle shaped with cornification of individual
      cells, a 2-fold increase in hsp27 expression was observed. A somewhat weaker
      increase in hsp27 mRNA was shown by Northern blot analysis. Our studies provide
      evidence that hsp27 is accumulated in a differentiation-dependent manner in human
      normal keratinocytes grown under conditions inducing terminal differentiation
      (0.03-1.00 mM Ca2+). Therefore, hsp27 can be regarded as a marker of
      differentiation in human normal keratinocytes.

PMID- 7524632
TI  - The physician as caregiver and researcher.
AB  - The physician might happen to play a double role in the clinical setting when he
      is the caregiver as well as the researcher for a patient at the same time. The
      dynamics and the ethical profile of the two relationships caregiver-patient and
      researcher-subject are different, and conflicts might arise: while the main
      responsibility of the caregiver is directed towards the patient "here and now",
      the researcher has a primary responsibility for future patients, the scientific
      community and the society at large. It has been suggested that in the clinical
      setting the researcher, provided that all the requirements for the ethical
      conduct of an experimentation be respected, has an "autonomy-in-trust", i.e. a
      wide discretional space in the decision-making process. While agreeing with such
      a proposal to some extent, we suggest that a more active and deeper participation
      of subjects in the experimental process, through an ongoing consent and joint
      decision-making process, would help in overcoming many possible conflicts.

PMID- 7524633
TI  - Nuclear 3,5,3'-triiodothyronine receptor binding in mononuclear blood cells from
      patients with malignant blood diseases and small cell carcinoma of the lung.
AB  - We have previously demonstrated enhanced daily turnover of thyroid hormones in
      patients with hypermetabolic symptoms due to malignant haematologic disorders or
      small cell carcinoma of the lung. We hypothesized that some of these symptoms
      might be due to enhanced peripheral effects of T3. We therefore studied the
      nuclear T3 receptor binding in circulating mononuclear blood cells in 5 patients
      with malignant haematologic disorders, 5 with untreated small cell carcinoma of
      the lung, and 11 healthy controls. Maximal binding capacity of T3 (MBC) was
      increased 2.5 times in the diseased patients, (median (range)) 110 fmol/mg DNA
      (75-519) in the haematologic group (p < 0.01), 106 fmol/mg DNA (47-490) (p <
      0.10) in small cell carcinoma patients, as compared to 43 fmol/mg DNA (26-94) in
      controls. The affinity constant Ka of bound T3 was reduced to one-third in the
      diseased patients. No differences were found between serum thyroid hormone or TSH
      levels. It is hypothesized, that previously demonstrated enhanced turnover of
      thyroid hormones in these states of disease might in part be due to increased
      peripheral consumption of thyroid hormones, including enhanced receptor binding
      of T3.

PMID- 7524627
TI  - Expression pattern of parathyroid hormone/parathyroid hormone related peptide
      receptor mRNA in mouse postimplantation embryos indicates involvement in multiple
      developmental processes.
AB  - In this paper we describe the cloning of the mouse Parathyroid
      Hormone/Parathyroid Hormone related Peptide Receptor (PTH/PTHrPR) cDNA and
      expression of its mRNA during mouse postimplantation development from day 5.5
      until day 15.5 post coitum (p.c.). In support of a model from previous studies,
      in which parietal endoderm differentiation is regulated by the interaction of the
      PTH/PTHrPR and Parathyroid Hormone related Peptide (PTHrP), high levels of
      PTH/PTHrPR mRNA levels were detected in developing parietal endoderm from day 5.5
      p.c. and onwards. In the embryo proper, PTH/PTHrPR mRNA expression was mainly
      detected at sites of epithelium/mesenchyme interactions, starting at day 9.5 p.c.
      in the epithelium of the intestine and later in the mesenchyme of the lung, the
      epithelium of meso- and metanephric tubuli, the dermis and at all sites where
      bone formation takes place. The complexity of the PTH/PTHrPR expression pattern
      suggests tight developmental regulation and indicates multiple roles in
      embryogenesis for the receptor and its ligands, not only in extraembryonic tissue
      but also in the formation of various organs.

PMID- 7524634
TI  - Direct effect of protirelin (TRH) on PB[123I] in autonomous thyroid adenoma.
AB  - In a retrospective study of 27 cases of iodine deficiency and/or latent primary
      hypothyroidism and in 16 cases of thyroid adenoma with hyperthyreosis the routine
      radioiodine uptake test was combined with a protirelin (TRH) test. After TRH
      infusion, [PB*I] and TSH increased significantly in all of these 27 patients who
      served as controls for the hyperthyroid patients. At the same time, the
      conversion rate Q rose in 14 of the control patients, but it dropped in 13 cases,
      thus indicating a TSH-induced discharge from the thyroid of radioiodine
      containing substances that were not bound to serum proteins. In nine of the 16
      patients with autonomous adenoma, PB[*I] rose slightly, but Q did not increase
      significantly. In seven of the 16 adenoma patients, both PB[*I] and Q even
      dropped slightly in the absence of measurable serum TSH, thus indicating a
      negative direct effect of TRH on thyroid hormone metabolism.

PMID- 7524636
TI  - Principals of limited or radical surgery for differentiated thyroid cancer.
AB  - Since the late sixties standard total thyroidectomy with or without selective
      radical neck dissection depending on the extent of the disease has become the
      routine surgical procedure for differentiated thyroid carcinoma (DTC;-papillary,
      follicular). This strategy has contributed remarkably to the increase of cure
      rates for various reasons. Only recently, in the last decade, has limited
      radicality with only unilateral lobectomy (= hemithyroidectomy) with or without
      partial contralateral resection been advocated as being sufficient for selected
      early tumor stages. We have analyzed a series of 252 patients, 174 (69%) being
      papillary and 78 (31%) follicular. Primary operation was done in 117 patients
      (46%) while 135 patients (54%) underwent reoperative surgery at this institution
      for either completion of radicality or because of loco-regional recurrence. From
      our evaluation we draw the conclusion that limited radicality (unilateral
      operation or subtotal) is justified only in pT-1-tumors in younger age (< 45 yrs)
      in order to avoid recurrence and unnecessary reoperation. On the other hand
      generous indication for reoperation is justified with the overall chance of
      almost 60% cure rate. All adjuvant treatment, mainly radioiodine should be
      applied thereafter.

PMID- 7524635
TI  - Surgical strategy for papillary carcinoma of the thyroid in an iodine rich area:
      decision on the operation table.
AB  - In iodine rich areas the incidence of papillary carcinoma of the thyroid is
      extremely high but its prognosis is favorable. When papillary carcinoma is
      confined to one lobe, our standard surgical procedure has been total lobectomy
      with isthmusectomy rather than total thyroidectomy. Our followup study of 185
      such patients reveals considerable difference in the outcome between the 85
      patients with gross thyroid capsular invasion and the 100 patients without,
      regardless of the presence of cervical lymph node metastasis. In the latter
      group, the tumor could be completely resected in all patients; although 4 cases
      had recurrence and required reoperation, 3 patients are alive and well and one
      died of other disease. In contrast, 20 patients in the former group had
      incomplete resection of the tumor, 4 patients developed recurrence and needed to
      be reoperated and 7 patients eventually died of thyroid cancer. One hundred
      thirty three patients (71.9%) underwent modified neck dissection at the time of
      surgery to find lymph node metastasis in 37 of 59 cases (62.7%) without gross
      thyroid capsular invasion and 64 of 74 cases (86.5%) with such invasion. The
      difference is statistically significant (P < 0.05). From these results we
      conclude that for papillary thyroid cancer in iodine rich areas total lobectomy
      with isthmusectomy is the treatment of choice when gross thyroid capsular
      invasion is not recognized on the operation table. However, when gross thyroid
      capsular invasion is recognized, total or near total thyroidectomy has to be
      performed.

PMID- 7524637
TI  - L-thyroxine malabsorption due to the injection of herbal remedies.
AB  - Two patients are described in whom the absorption of l-thyroxine was impaired by
      non-prescription herbal and nutritional remedies. The absorption of thyroid
      hormones is discussed and an approach to the problem of patients who appear to be
      unresponsive to the usual doses of thyroid hormones is suggested.

PMID- 7524638
TI  - Human fibroblasts (KMST-6/RAS line) transformed with 60Co gamma-rays and c-Ha-ras
      oncogene constitutively produce a large amount of human granulocyte-colony
      stimulating factor (G-CSF).
AB  - Human fibroblasts (KMST-6/RAS) transformed with 60Co gamma-rays and the Ha-ras
      oncogene formed tumors in nude mice. These mice showed splenomegaly and an
      increase in granulocytes in the peripheral blood. There was a direct correlation
      between tumor size and spleen size. Histologically, prominent proliferation of
      granulocytes was observed in the enlarged spleen. These findings indicated that
      KMST-6/RAS cells might have been producing granulocyte colony-stimulating factor
      (G-CSF) in the nude mice. In fact, in vitro studies demonstrated that the cells
      produced G-CSF in the culture medium and that production of G-CSF was greater
      during the logarithmic growth than during the stationary phase. Nearly equal
      amounts of G-CSF were produced by cells grown in serum-free or 10% serum
      supplemented medium. Neither expression of the ras oncogene nor the
      tumorigenicity of cells correlated with the production of G-CSF. G-CSF production
      in KMST-6/RAS cells was significantly stimulated by butyrate, but not by
      dexamethasone or 5-azacytidine.

PMID- 7524639
TI  - [A new liver support system composed of functional human cells and a radial-flow
      bioreactor].
AB  - An artificial liver will be useful for the treatment of acute hepatic failure and
      a bridge of liver transplantation. The current reports suggest that the hybrid
      type of artificial liver composed of functional human liver cells and a
      bioreactor is practical for clinical use. In the present study, we succeeded high
      density culture on a large-scale of human functional hepatoma (JHH-7) using a
      newly developed radial flow packed-bed bioreactor. Since the shear stress of this
      bioreactor is lower than the other type, high density culture without cell damage
      is possible. JHH-7 cells produced large amounts of human albumin and other liver
      specific proteins, and then have the function of ammonia metabolism in the
      system. This study suggests that a radial flow bioreactor will be developed as a
      new type of artificial liver.

PMID- 7524642
TI  - Analysis of T cell antigen receptors of myelin basic protein specific T cells in
      SJL/J mice demonstrates an alpha chain CDR3 motif associated with
      encephalitogenic T cells.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal autoimmune disease
      mediated by CD4+ T cells. Analysis of TCR expression revealed that limited TCR
      elements (V beta 8.2, V alpha 2 or 4) were utilized by myelin basic protein (MBP)
      specific T cells in mice with H-2u haplotype and Lewis rats. The usage of a
      particular beta chain complementarity determining region 3 (CDR3) motif has also
      been shown. However, it remains unclear to what extent these observations can be
      extrapolated. Here we studied the TCR sequences of MBP 89-101/I-A(s) specific T
      cell clones derived from SJL/J mice, using the polymerase chain reaction on
      reverse transcribed mRNA. Although the V beta usage was less restricted than in H
      2u mice, they predominantly utilized V beta 17a and expressed LGG or related
      motifs in the V beta-D beta-J beta junctions. Furthermore, a single alpha chain
      rearrangement between V alpha 1.1 and J alpha BBM142 with no N region diversity
      was preferentially used. Concordantly, immunization with a peptide corresponding
      to the alpha chain CDR3 was found to significantly alter the clinical course of
      EAE. Comparison of the published TCR junctional regions demonstrates that the
      CDR3 motifs (LGG in beta chain, CA*R*NY motif in alpha chains) are expressed by
      other encephalitogenic clones. Notably, the CA*R*NY was conserved in PL/J mice
      clones that recognize a distinct MBP-MHC determinant. It suggests that an antigen
      independent mechanism may contribute to conserving the alpha chain motif. The
      implications of these observations are discussed.

PMID- 7524641
TI  - Heat-stable antigen (CD24) as ligand for mouse P-selectin.
AB  - Heat-stable antigen (HSA)/CD24 is a cell surface molecule expressed by many cell
      types in the mouse. The molecule has an unusual structure because of its small
      protein core and extensive glycosylation. In order to study the functional role
      of the HSA-associated glycoconjugates we have isolated different forms of HSA.
      Using lectin analysis we provide evidence for extensive heterogeneity in
      carbohydrate composition and sialic acid linkage. Several HSA forms were
      recognized by mouse P-selectin-IgG but not E-selectin-IgG in ELISA. As expected,
      P-selectin-IgG also bound to L2/HNK-1-positive neural glycoproteins (L2
      glycoproteins) and sulfatides but not to gangliosides and other control
      glycoproteins. The binding of P-selectin-IgG to L2-glycoproteins and HSA required
      bivalent cations. The reactivity to HSA was sensitive to sialidase treatment
      whereas the binding to L2-glycoproteins was not. Studies with alpha 2-6
      sialytransferase indicated that alpha 2-6 linked sialic acid was not involved in
      the P-selectin binding to HSA. Surprisingly, an L2/HNK-1 specific antibody was
      found to cross-react with some HSA glycoforms and its binding correlated with P
      selectin-IgG reactivity. L2/HNK-1-positive or L2/HNK-1-negative HSA glycoforms
      were also analyzed after coating to polystyrene beads. Only the L2/HNK-1-positive
      HSA coated beads were reactive with P-selectin-IgG and could bind to activated
      bend3 endothelioma cells expressing P-selectin whereas the L2/HNK-1-negative HSA
      beads did not. It is suggested that in its L2/HNK-1 modified form the HSA
      molecule on leukocytes could represent a ligand for P-selectin on endothelial
      cells or platelets.

PMID- 7524644
TI  - Doubts using family history, age, alpha-fetoprotein and total human chorionic
      gonadotrophin in screening for Down's syndrome.

PMID- 7524640
TI  - Decreased surface IgM receptor-mediated activation of phospholipase C gamma 2 in
      B-1 lymphocytes.
AB  - Intracellular signaling triggered by the antigen receptor of primary B-1 (CD5+ B)
      lymphocytes is insufficient to bring about cell cycle progression to S phase;
      this appears to result from a block in signal propagation prior to the activation
      of protein kinase C. The present studies were undertaken to evaluate specific
      elements in the proximal portion of the intracellular signaling cascade to
      determine the basis for aberrant signal transduction in B-1 cells. There was no
      evidence for an alteration in src kinase composition or for diminished receptor
      mediated tyrosine phosphorylation on the part of B-1 cells. Further,
      phospholipase C gamma 2 was inducibly tyrosine phosphorylated following surface
      Ig ligation. However, the receptor mediated increase in enzymatic activity of
      immunoprecipitated phospholipase C gamma 2 was markedly diminished in B-1 as
      compared with B-2 cells. These results indicate that phospholipase C gamma 2
      largely fails to become activated following surface Ig receptor interaction in B
      1 cells and suggest that this enzyme may be directly involved in controlling the
      propagation of progression signals.

PMID- 7524645
TI  - Hepatitis C seroconversion in pregnancy.

PMID- 7524643
TI  - Effect of a derivatized dextran on human osteoblast growth and phenotype
      expression.
AB  - Water soluble derivatized dextran named E9 with a molecular weight of 45,000 g l
      1 containing 58% methyl carboxylic acid unit, 19% benzylamide unit, and 26%
      sulfonate with a specific anticoagulant activity of 0.29 IU mg-1 was studied for
      its effects on human osteoblast growth and phenotype expression for short-term
      treatment. At concentrations between 1 ng ml-1 and 1 microgram ml-1 E9 has no
      effect on DNA synthesis whereas at higher concentrations DNA synthesis is
      inhibited in a dose related fashion (87% for 400 micrograms ml-1). For
      concentrations which do not modify osteoblast growth, E9 promotes alkaline
      phosphatase activity, type I collagen and osteocalcin synthesis with a maximum
      effect for 0.1-1 microgram ml-1. It has a synergistic effect with hPTH increasing
      AMPc. Moreover, osteonectin synthesis was enhanced in a dose-dependent manner
      between 0.1 and 5 micrograms ml-1. These results seem to indicate that E9 is able
      to stimulate human osteoblast phenotype expression and could be useful in
      clinical applications.

PMID- 7524646
TI  - Haematological risk factors for pregnancy outcome in Jamaican women with
      homozygous sickle cell disease.
AB  - OBJECTIVE: To examine the association between fetal outcome and the steady state
      haematology of mothers with homozygous sickle cell disease. DESIGN: A
      retrospective observational study. The data were taken from dockets kept at the
      Sickle Cell Clinic and verified by interview with 45% of the patients. SETTING:
      The Sickle Cell Clinic at the University Hospital of the West Indies or two
      peripheral clinics operated by the staff of the MRC Laboratories. SUBJECTS: All
      women aged 14 years or older with homozygous sickle cell disease who had
      experienced at least one pregnancy in the period 1977 to 1986. MAIN OUTCOME
      MEASURES: Three fetal outcomes including miscarriages, perinatal deaths, and
      birthweight. RESULTS: There were 270 singleton pregnancies in 175 women with an
      overall fetal wastage of 32.2%. There was a significant increased risk of
      perinatal death with low maternal fetal haemoglobin level, but there were no
      haematological associations with miscarriages or birthweight. CONCLUSIONS: These
      data suggest that maternal steady-state haematology has little influence on fetal
      outcome, with the exception that mothers with high HbF levels are less prone to
      perinatal deaths. Further study is required to investigate acute haematological
      changes associated with pregnancy.

PMID- 7524648
TI  - Bilateral osteochondral loose bodies of the temporomandibular joints with
      unilateral enlargement of condyle.

PMID- 7524647
TI  - Clustering of perinatal markers of birth asphyxia and outcome at age five years.
AB  - OBJECTIVES: In a cohort of term infants with cerebral depression at delivery, to
      investigate the association of perinatal signs of birth asphyxia, particularly
      abnormal fetal heart rate patterns in labour, acidaemia, and serious neonatal
      encephalopathy, with neurodevelopmental outcome at age five years. DESIGN: Five
      year follow up study of a birth cohort. SETTING: Regional maternity hospital.
      SUBJECTS: One hundred and eighty-four singleton infants with a 1 min Apgar score
      < or = 3, born at term between January 1984 and September 1985. MAIN OUTCOME
      MEASURES: Neonatal death, cerebral palsy, and scores on a battery of
      neurodevelopmental tests at age five. RESULTS: Seven infants had a cluster of
      perinatal signs suggestive of birth asphyxia; all included serious neonatal
      encephalopathy. Three of these infants died neonatally, three had spastic
      quadriparesis with profound developmental delay, and one was unimpaired at the
      age of five. Among the remaining infants, no association was found between
      severely abnormal fetal heart rate patterns in labour and scores on
      neurodevelopmental tests, or between acid-base status at delivery and test
      scores. CONCLUSIONS: Birth asphyxia, identified by a cluster of abnormal
      perinatal signs, including serious neonatal encephalopathy, has a poor prognosis.
      If serious encephalopathy is not present, cerebral depression at birth preceded
      by abnormal fetal heart rate patterns in labour, or with acid-base derangement,
      is not predictive of later impairment.

PMID- 7524649
TI  - The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of
      proatherogenic and proinflammatory proteins in human endothelial cells.
AB  - The mechanisms by which dietary fatty acids can modulate atherogenesis and
      inflammation are poorly understood. Induction in endothelial cells of adhesion
      molecules for circulating leukocytes and of inflammatory mediators by cytokines
      probably contributes to the early phases of atherogenesis and inflammation. We
      report here that incorporation into cellular lipids of docosahexaenoic acid
      (DHA), a specific fatty acid of the omega 3 family, decreases cytokine-induced
      expression of endothelial leukocyte adhesion molecules, secretion of inflammatory
      mediators, and leukocyte adhesion to cultured endothelial cells. DHA, but not
      eicosapentaenoic acid, decreased in a dose- and time-dependent fashion the
      expression of vascular cell adhesion molecule 1 (VCAM-1) induced by interleukin
      (IL)-1, tumor necrosis factor (TNF), IL-4, or bacterial lipopolysaccharide, with
      half-maximum inhibition at < 10 mumol/L. This reduction required prolonged (24-
      to 96-hour) exposure of endothelial cells to DHA and correlated with the degree
      of DHA incorporation into cellular lipids. DHA also limited cytokine-stimulated
      endothelial cell expression of E-selectin and intercellular adhesion molecule 1
      and the secretion of IL-6 and IL-8 into the medium but not the surface expression
      of constitutive surface molecules. Cyclooxygenase inhibition did not block the
      effect of DHA on VCAM-1. In parallel with reduced surface VCAM-1 protein
      expression, DHA reduced VCAM-1 mRNA induction by IL-1 or TNF. DHA treatment also
      reduced the adhesion of human monocytes and of monocytic U937 cells to cytokine
      stimulated endothelial cells. These properties of DHA may contribute to
      antiatherogenic and anti-inflammatory effects of omega 3 fatty acids.

PMID- 7524650
TI  - [Detection of tenascin in stomach cancer. An immunohistochemical study].
AB  - Tenascin, a glycoprotein of the extracellular matrix, is involved in epithelial
      proliferation, differentiation and cell migration during embryonic development.
      Later on, it is important in proliferative processes like tumor growth and wound
      healing. We examined the distribution of tenascin, especially in the stroma near
      basement membranes, in paraffin sections from 25 patients with gastric cancer by
      immunohistological staining with regard to tumor staging, grading and Lauren
      classification. In two series we used a monoclonal and a polyclonal antibody
      against human tenascin. In most of the sections there was a more intensive
      staining of the surrounding stroma in areas close to the tumor, which could
      indicate the direction of tumor growth. In highly differentiated tumors we found
      a positive, yet discontinuous staining close to the basement membrane. In
      contrast to this, we saw a more diffuse reaction of the stroma with network-like
      staining of the collagen fibres in undifferentiated tumors. In lymph nodes we
      also detected a small number of tumor cells by staining of the surrounding
      stroma.

PMID- 7524651
TI  - The apocrine carcinoma of the breast. A cytological, immunohistochemical and
      ultrastructural study of 6 cases.
AB  - The apocrine carcinoma is a rare type of invasive breast carcinomas.
      Characteristic features of this neoplasm are shown by the eosinophilic granular
      cytoplasm with apical snouts and strong expression of GCDFP-15. A review of 2000
      available primary breast carcinomas identified 6 examples (0.3%) based on the
      definition. Architecturally, these tumors displayed either a solid-tubular or a
      papillary growth pattern, while cytologically the lesions were composed of large
      columnar epithelial cells with marked anisonucleosis and numerous PAS-positive
      diastase-resistant cytoplasmic granules. Immunohistochemically, apocrine breast
      carcinomas showed abundant GCDFP-15, CEA an c-erbB-2 oncoprotein. Electron
      microscopic analysis revealed the presence of numerous secretory granules. The
      differential diagnostic problems of apocrine breast carcinomas and malignant
      tumors mimicking them are discussed.

PMID- 7524653
TI  - Expression of intermediate filaments in normal and neoplastic exocrine pancreas.
AB  - The intermediate filament (IF) proteins present in the normal and pathological
      exocrine human pancreas were studied by immunolocalization using antibodies to
      cytokeratins (CKs) and vimentin. Acinar cells of normal pancreas showed a
      presence of simple CKs 8 and 18. Duct epithelium consistently expressed CKs 7, 8,
      18 and 19 whereas centroacinar cells were rather low in CK 7. A subpopulation of
      CK 4 cells was detected in inter-intralobular ducts. In addition, some ducts
      contained individual cells or groups of cells that were positive for the
      stratification-related CKs (CKs 4, 5, 13, 15, 16). All pancreatic ductal
      adenocarcinomas regularly expressed CKs 7, 8, 18, 19 and were also positive for
      the 34 beta E12 antibody. Cytokeratin 4 was detected in a minor population of
      tumor cells. Pancreatic carcinoma also contained minor amounts of stratification
      related CKs in variable combinations. Mucinous cystoadenocarcinoma showed the
      presence of CKs 7, 8, 18, 19 and was also positive for 34 beta E12, whereas the
      serous microcystic tumor presented CKs 8, 18, 19 and a variable amount of CKs 4
      and 7. The duct-ductular alterations of the exocrine pancreas contained a
      different combination and distribution of CK isoforms similar to normal
      pancreatic ductal system. Mucinous hypertrophy and pyloric gland metaplasia
      reacted with antibodies to CKs 7, 8, 18 and 19. Vimentin was focally present both
      in normal and neoplastic tissue. Our results indicate that pancreatic ducts are
      characterized by an intrinsic "biliary-pancreatic duct type" immunoprofile (CKs
      7, 8, 18 and 19), in contrast to acinar cells expressing exclusively CKs 8 and
      18. We also detected a subpopulation of ducts regularly expressing CK 4.
      Surprisingly, several stratification-related CKs were detected both in normal and
      neoplastic exocrine pancreas. Moreover, the differentiation phenotypes of
      pancreatic tumors were reminiscent of normal cellular compartments.

PMID- 7524654
TI  - Degradation of glucosinolates during in vitro incubations of rapeseed meal with
      myrosinase (EC 3.2.3.1) and with pepsin (EC 3.4.23.1)-hydrochloric acid, and
      contents of porcine small intestine and caecum.
AB  - Changes in the concentrations of glucosinolates from rapeseed meal and some
      glucosinolate degradation products during incubation in vitro with myrosinase (EC
      3.2.3.1), with pepsin (EC 3.4.23.1)-HCl, and with contents of porcine small
      intestine and caecum were studied. When rapeseed meal was incubated with
      myrosinase, 5-vinyl oxazolidinethione (OZT) and butenyl and pentenyl
      isothiocyanates were produced; OZT concentration rose to a plateau after about 2
      h. However, when incubated with caecal contents only OZT could be detected; its
      concentration peaked after about 4-5 h then declined. Under in vitro conditions
      which attempted to simulate peptic and small intestinal digestion no OZT could be
      detected; the individual glucosinolates differed in susceptibility to peptic
      conditions, losses ranging from 3 to 23%. Under the small intestinal conditions
      the losses of individual glucosinolates ranged from about 7 to 28%. Addition of
      CuSO4, ascorbic acid, tylosin or a probiotic had little effect on the outcome of
      peptic or small intestinal incubations but tylosin appeared to slow the
      degradation of glucosinolates in the presence of caecal contents.

PMID- 7524652
TI  - Cytokeratins and mucins as molecular markers of cell differentiation and
      neoplastic transformation in the exocrine pancreas.
AB  - Acinar and ductal cells of the normal pancreas express cytokeratin (CK) patterns
      which indicate a heterogeneity of ductal epithelia. On account of the CK of
      pancreatic adenocarcinoma, it would seem to be probable that tumor epithelia
      possess a considerable potential for squamous epithelium metaplasia. Comparative
      studies of CK expression by ductal carcinoma of the pancreas and carcinoma of
      bile ducts, stomach and large intestine as well in cases of chronic pancreatitis
      have demonstrated the usefulness of CK for differential diagnosis of these
      conditions. From the number of apomucins, mainly MUC1 is produced in the normal
      pancreas. This capacity is maintained in pancreas carcinoma and cell lines
      derived from it.

PMID- 7524655
TI  - Projection structure of the CHIP28 water channel in lipid bilayer membranes at 12
      A resolution.
AB  - Osmotic water transport across plasma membranes in erythrocytes and several
      epithelial cell types is facilitated by CHIP28, a water-selective membrane
      channel protein. In order to examine the structure of CHIP28 in membranes, large
      (1.5-2.5-microns diameter), highly ordered, two-dimensional (2-D) crystals of
      purified and deglycosylated erythrocyte CHIP28 were generated by reconstitution
      of detergent-solubilized protein into synthetic lipid bilayers via detergent
      dialysis. Fourier transforms computed from low-dose electron micrographs of such
      crystals preserved in negative stain display order to 12-A resolution. The
      crystal lattice is tetragonal (a = b = 99.2 +/- 1.4 A) with plane group symmetry
      p4g. A projection density map at 12-A resolution defines the molecular boundary
      and organization of the CHIP28 monomers in the membrane plane. The unit cell
      contains four CHIP28 dimers, each composed of two oblong-shaped (37 x 25 A )
      monomers with opposite orientations. The CHIP28 monomers associate to form
      tetrameric structures around the 4-fold axes normal to the membrane plane where
      stain is excluded. The 2-D crystals of CHIP28 display order extending beyond the
      limit typically achieved by negative staining and therefore may be amenable to
      high-resolution structure analysis by cryo-electron microscopy.

PMID- 7524656
TI  - Arachidonic acid and lipoxygenase products stimulate gonadotropin alpha-subunit
      mRNA levels in pituitary alpha T3-1 cell line: role in gonadotropin releasing
      hormone action.
AB  - The role of arachidonic acid (AA) and its lipoxygenase metabolites in
      gonadotropin releasing hormone (GnRH) induced alpha-subunit gene expression was
      investigated in the transformed gonadotroph cell line alpha T3-1. The stable
      analog [D-Trp6]GnRH (GnRHa) stimulated [3H]AA release from prelabeled cells after
      a lag of 1-2 min. Addition of AA stimulated alpha-subunit mRNA levels in a dose
      dependent manner, a significant effect being detected at 5 microM AA. Among
      various lipoxygenase metabolites of AA, only the 5-lipoxygenase products 5
      hydroxyeicosatetraenoic acid (5-HETE) and leukotriene C4 (LTC4) stimulated alpha
      subunit mRNA levels. However, while 5-HETE and LTC4 (0.1 nM each) were active
      already after 30 min of incubation, similar to GnRHa, AA (20 microM) stimulated
      alpha-mRNA levels after 1 h of incubation. Addition of the phospholipase A2
      inhibitor 4-bromophenacyl bromide (BPB) or the selective 5-lipoxygenase inhibitor
      L-656,224 inhibited GnRHa elevation of alpha-subunit mRNA by 65%, while the
      cyclooxygenase inhibitor indomethacin had no effect. Addition of AA (20 microM)
      or LTC4 (0.1 nM) to normal cultured rat pituitary cells mimicked the rapid (30
      min) stimulatory effect of GnRH (1 nM) upon alpha-subunit, LH beta, and FSH beta
      mRNA levels, while 5-HETE (0.1 nM) stimulated only FSH beta mRNA levels at this
      time point. Thus AA and selected 5-lipoxygenase products, in particular LTC4,
      participate in GnRHa-induced alpha-subunit mRNA elevation.

PMID- 7524657
TI  - The (DD)E complex is maintained by a composite fibrin polymerization site.
AB  - The (DD)E complex is the major cross-linked fibrin degradation fragment.
      Structural components required for maintenance of the (DD)E complex were examined
      in order to better understand clot structure and the contribution of specific
      polypeptide chain segments in the process of polymerization. First, the (DD)E
      complex was reversibly dissociated by peptides derived from the alpha-chain NH2
      terminus of fibrin having a minimal sequence of GPR (alpha 17-19). In addition,
      the complex was partially dissociated by peptide beta 40-54, while beta 50-55 and
      peptides derived from the fibrin beta-chain NH2-terminus had no effect. Second,
      monoclonal antibody (mAb) 1B6, specific for the alpha-chain NH2-terminus of
      fibrin, reacted rapidly with fragment E1, but did not recognize the corresponding
      epitope on the (DD)E complex. On the other hand, mAb 59D8, specific for GHRPL at
      the beta-chain NH2-terminus of fibrin, reacted with the (DD)E complex in a dose
      dependent manner. Third, the (DD)E complex was irreversibly dissociated by
      proteolytic cleavage of fragment E1 by either thrombin, which removed GPR from
      the alpha-chain NH2-terminus, or Crotalus atrox protease III, which released beta
      15-42. It has been concluded that fragment E1 contains a composite polymerization
      site consisting at least of residues alpha 17-19 and beta 20-49, which together
      maintain the (DD)E complex. These results illustrate that the complex is kept
      together by complementary binding sites which form a nucleus of linear fibrin
      polymerization sites. The (DD)E complex can thus be considered as a soluble model
      of fibrin clot.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524658
TI  - Detection of coexisting fluid phospholipid phases by equilibrium Ca2+ binding:
      peptide-poor L alpha and peptide-rich HII phase coexistence in gramicidin
      A'/phospholipid dispersions.
AB  - The isothermal phase behavior of three gramicidin A'/phospholipid mixtures was
      investigated by an equilibrium Ca(2+)-binding technique. The phospholipid
      component was 1,2-dioleoyl-sn-glycero-3-phosphoserine (DOPS), 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphoserine (POPS), or POPS/1-palmitoyl-2-oleoyl-sn-glycero
      3-phosphocholine (POPC) at a constant mole ratio of 1/4. The bulk aqueous free
      Ca2+ concentration, [Ca2+]*f, in equilibrium with one or two gramicidin
      A'/phospholipid fluid phases and a small amount of the Ca (phosphatidylserine)2
      gel phase, was measured as a function of composition at 20 degrees C by use of
      chromophoric high-affinity Ca2+ chelators. The coexistence of two gramicidin
      A'/phospholipid fluid phases was detected by an invariance in [Ca2+]*f over the
      range of compositions throughout which the two phases coexist. The compositions
      of the two coexisting phases are determined by the compositions at which the
      invariance in [Ca2+]*f begins and ends. With each of the gramicidin
      A'/phospholipid mixtures, we estimate that the composition of the gramicidin-poor
      phase is 0.03-0.04 mole fraction gramicidin A' and the composition of the
      gramicidin-rich phase is 0.13-0.14 mole fraction gramicidin A'. Characterization
      of these phases by low-angle X-ray diffraction revealed that, in each case, the
      gramicidin-poor phase is an L alpha phase and the gramicidin-rich phase is an HII
      phase. The isothermal phase behavior of gramicidin A'/POPC mixtures at
      approximately 23 degrees C, as determined by low-angle X-ray diffraction, was
      found to be similar to that of the other gramicidin A'/phospholipid
      mixtures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524660
TI  - Characterization of a fluorescent substance P analog.
AB  - We describe the development and characterization of substance P labeled at Lys3
      with fluorescein ([fluorescein Lys3]SP) as a fluorescent probe for the neurokinin
      1 (NK1) receptor. [fluorescein Lys3]SP is an agonist at the human NK1 receptor,
      with an affinity for both the high-affinity and low-affinity binding states of
      the receptor approximately 6-fold lower than that of substance P. Binding of the
      probe to the human NK1 receptor expressed in Sf9 insect cells was observed
      directly by monitoring either a decrease in fluorescence intensity or an increase
      in anisotropy of the [fluorescein Lys3]SP. Detection by anisotropy gave the
      larger signal and thus was used to characterize the interaction of [fluorescein
      Lys3]SP with the receptor. The anisotropy of the bound ligand was 0.17, compared
      to 0.04 for the free ligand. The fluorescence was quenched by about 15% upon
      binding to the receptor. Bound [fluorescein Lys3]SP was displaced by unlabeled SP
      and by the quinuclidine antagonist L-703,606. As expected for an agonist, binding
      was also reduced by the addition of the nonhydrolyzable guanine nucleotide analog
      GppNHp. [fluorescein Lys3]SP should provide a useful structural and kinetic probe
      for the NK1 receptor.

PMID- 7524661
TI  - Gliotoxin stimulates Ca2+ release from intact rat liver mitochondria.
AB  - Gliotoxin is an epidithiodioxopiperazine compound which can both react with
      sulfhydryl groups and form hydrogen peroxide. Rat liver mitochondria contain a
      prooxidant-regulated specific Ca2+ release pathway. Here we report that gliotoxin
      at low concentrations stimulates Ca2+ release via this pathway in isolated
      mitochondria. Ca2+ release is not promoted by gliotoxin exposed to disulfide
      reducing reagents prior to addition to mitochondria or when its disulfide moiety
      is dimethylated. Gliotoxin is equally effective in glutathione-depleted and
      glutathione-adequate mitochondria. This and the unchanged mitochondrial oxygen
      consumption in the presence of gliotoxin suggest that the compound stimulates
      Ca2+ release by reacting with critical mitochondrial thiol compounds and not by
      increasing hydrogen peroxide formation in mitochondria. The gliotoxin-induced
      Ca2+ release is paralleled by hydrolysis of mitochondrial pyridine nucleotides,
      and both pyridine nucleotide hydrolysis and Ca2+ release are inhibited by
      cyclosporin A. These findings provide further insight into the regulation of Ca2+
      release from intact mitochondria.

PMID- 7524659
TI  - Na+/H+ exchanger-2 is an O-linked but not an N-linked sialoglycoprotein.
AB  - A polyclonal antibody (Ab597) was produced in rabbit against a fusion protein of
      glutathione-S-transferase and the last 87 amino acids of the Na+/H+ exchanger
      isoform, NHE2. By Western blotting, Ab597 recognized proteins of 75 and 85 kDa in
      PS120/NHE2 membranes (PS120 cells stably transfected with NHE2), and this
      antibody did not cross-react with NHE1 and NHE3. When Ab597 was used to
      immunocytochemically stain PS120/NHE2 cells, permeabilization of the cells was
      required for staining, confirming the putative membrane topology of NHE2 that the
      C-terminus is cytoplasmic. NHE1 is N-glycosylated. NHE2 was predicted to be N
      glycosylated as it contains one potential N-linked glycosylation site (N350VS),
      which is conserved among NHE1, NHE3, and NHE4. However, NHE2 was resistant to
      peptide:N-glycosidase F (PNGase F) and endoglycosidase H (Endo H) digestion,
      suggesting that NHE2 is not N-glycosylated. In contrast, neuraminidase shifted
      the mobility of the 85 kDa NHE2 protein in PS120/NHE2 membranes into an 81 kDa
      band, and O-glycanase further shifted the mobility of the neuraminidase-treated
      81 kDa protein to 75 kDa. Incubation of PS120/NHE2 cells with benzyl N-acetyl
      alpha-D-galactosaminide (Bz alpha GalNAc), an O-glycosylation inhibitor,
      decreased the size of the 85 kDa protein to 81 kDa. This treatment had no effect
      on the initial rate of Na+/H+ exchange of PS120/NHE2 cells. The 75 kDa protein
      was not affected by the glycosidase treatment of PS120/NHE2 membranes or the Bz
      alpha GalNAc treatment of PS120/NHE2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524662
TI  - Solution structure of FK506 bound to the R42K, H87V double mutant of FKBP-12.
AB  - The binding of the FK506/FKBP-12 complex to calcineurin (CN), its putative target
      for immunosuppression, involves recognition of solvent-exposed regions of the
      ligand as well as FKBP-12 residues near the active site. The R42K, H87V double
      mutation of FKBP-12 decreases the CN affinity of the complex by 550-fold [Aldape,
      R. A., Futer, O., DeCenzo, M. T., Jarrett, B. P., Murcko, M. A., & Livingston, D.
      J. (1992) J. Biol. Chem. 267, 16029-16032]. This work reports the solution
      structure of 13C-labeled FK506 bound to R42K, H87V FKBP-12. Assignments and NOE
      measurements at three mixing times were made from inverse-detected 1H-13C NMR
      experiments. Structures were calculated by several different methods, including
      distance geometry, restrained molecular dynamics, and molecular dynamics with
      time-averaged restraints. The NMR structures of the ligand are very well defined
      by the NOE restraints and differ slightly from the X-ray structure in regions
      that are involved in crystal packing. Comparison with the NMR structure of FK506
      bound to wild-type FKBP-12 reveals that the R42K, H87V mutation causes the ligand
      backbone near C16 to move by 2.5 to 4.5 A, reorients 15-MeO by 90 degrees, and
      shifts 13-MeO by approximately 1.5 A. FK506 appears to undergo a concerted,
      mutationally induced shift in the binding pocket, with the greatest changes
      occurring in the effector region of the drug. The altered effector conformation
      of mutant-bound FK506 may perturb interactions between the drug and CN, thus
      accounting for the effect of the double mutation upon the CN inhibitory activity
      of the complex.

PMID- 7524663
TI  - Resonance assignments and solution structure of the second RNA-binding domain of
      sex-lethal determined by multidimensional heteronuclear magnetic resonance.
AB  - The RNA-binding protein Sex-lethal (Sxl) is a critical regulator of sexual
      differentiation and dosage compensation in Drosophila. This regulatory activity
      is a consequence of the ability of Sxl to bind uridine-rich RNA tracts involved
      in pre-mRNA splicing. Sxl contains two RNP consensus-type RNA-binding domains
      (RBDs). A structural study of a portion of Sxl (amino acids 199-294) containing
      the second RNA-binding domain (RBD-2) using multidimensional heteronuclear NMR is
      presented here. Nearly complete 1H, 13C, and 15N resonance assignments have been
      obtained from 15N- and 13C/15N-uniformly labeled protein. These assignments were
      used to analyze 3D 15N-separated NOESY and 13C/13C-separated 4D NOESY spectra
      which produced 494 total and 169 long-range NOE-derived distance restraints.
      Along with 41 backbone dihedral restraints, these distance restraints were
      employed to generate an intermediate-resolution family of calculated structures,
      which exhibits the beta alpha beta-beta alpha beta tertiary fold found in other
      RBD-containing proteins. The RMSD to the average structure for the backbone atoms
      of residues 11-93 is 1.55 +/- 0.30 A, while the RMSD for backbone atoms involved
      in secondary structure is 0.76 +/- 0.14 A. A capping box [Harper, E.T., & Rose,
      G.D. (1993) Biochemistry 32, 7605-7609] was identified at the N-terminus of the
      first helix and has been characterized by short- and medium-range NOEs. Finally,
      significant structural similarities and differences between Sxl RBD-2 and other
      RBD-containing proteins are discussed.

PMID- 7524664
TI  - Recombinant HIV-1 nucleocapsid protein accelerates HIV-1 reverse transcriptase
      catalyzed DNA strand transfer reactions and modulates RNase H activity.
AB  - The effect of recombinant nucleocapsid protein (NCp7) from human immunodeficiency
      virus type 1 (HIV-1) on HIV-1 reverse transcriptase (HIV-1 RT) catalyzed DNA
      strand transfer reactions has been studied using kinetic methods with a defined
      template--primer model system. NCp7 is shown to modulate both the rate and the
      efficiency of DNA strand transfer synthesis. Evidence is presented that supports
      the role of NCp7 in catalyzing the annealing of a nascent DNA intermediate and
      RNA acceptor template during strand transfer. NCp7 was also found to enhance the
      ribonuclease H activity of HIV-1 RT and change the specificity of RNA hydrolysis,
      suggesting a direct role of NCp7 in HIV-1 RT catalyzed strand transfer. The
      implications of these findings for retroviral reverse transcription are
      addressed.

PMID- 7524665
TI  - The 2,6-diaminopurine riboside.5-methylisocytidine wobble base pair: an
      isoenergetic substitution for the study of G.U pairs in RNA.
AB  - Phylogenetically invariant G.U wobble pairs are present in a wide variety of
      RNA's. As a means to study the contribution of individual chemical groups within
      a G.U pair, we have synthesized and thermodynamically characterized
      oligoribonucleotides containing the unnatural nucleosides 2,6-diaminopurine
      riboside (DAP) and 5-methylisocytidine (MeiC). The DAP.MeiC pair at the end of an
      RNA duplex is as stable as a G.U pair, consistent with formation of a wobble base
      pair with two hydrogen bonds. DAP.MeiC is a valuable substitution for the study
      of G.U wobble pairs because it is conformationally similar to the G.U pair, but
      has a different array of functional groups in the major and minor grooves of the
      duplex and a reversed hydrogen bonding polarity between the bases. We also report
      the stability of several other terminal pairs proposed to be in a wobble
      configuration including inosine.U (I.U), A.MeiC, DAP.C, A.C, G.5-methyl-U,2'
      deoxyguanosine.U, and 2'-deoxy-7-deazaguanosine.U. These pairs present a
      diversity of functional group substitutions in the context of a wobble
      conformation. Comparison of wobble pairs with and without the N2 exocyclic amine,
      i.e., G.U vs I.U, DAP.MeiC vs A.MeiC, and DAP.C vs A.C, demonstrates that the
      amine does not contribute to base pairing stability when the pair is located at
      the terminal position of the RNA duplex. However, at a position internal to the
      duplex, the exocyclic amine does improve helix stability. An internal I.U pair is
      less stable (approximately 1 kcal.mol-1) than an internal G.U pair, and
      substantially less stable (approximately 2 kcal.mol-1) than an internal A-U pair.
      These data provide quantitation for the reduced duplex stability observed upon
      conversion of A-U to I.U pairs by double-stranded RNA adenosine deaminase
      (dsRAD). This collection of wobble pairs will help identify the contribution made
      by individual functional groups in RNA/protein interactions and in the tertiary
      folding of RNA.

PMID- 7524667
TI  - Activity of the hammerhead ribozyme upon inversion of the stereocenters for the
      guanosine 2'-hydroxyls.
AB  - Two guanosine 2'-hydroxyls in the hammerhead RNA complex at positions G5 and G8
      are critical for efficient cleavage by this RNA catalyst. These two functional
      groups are likely involved in the binding of the metal cofactor, or they are
      involved in specific interresidue hydrogen-bonding interactions. The importance
      of the stereochemical positioning of both critical 2'-hydroxyls was investigated
      by comparing the cleavage rates of three arabinosylguanine-substituted complexes
      (in which the positions of specific guanosine 2'-hydroxyls were stereochemically
      altered by inverting the C2' stereocenter) with that of the native complex, as
      well as with the rates of the dG- and dFG-substituted complexes [in which the 2'
      hydroxyls are absent as the result of substitution by 2'-deoxyguanosine (dG) or
      2'-deoxy-2'-fluoroguanosine (dFG)]. The G5araG and G8araG complexes exhibit
      dramatically different cleavage rates. The G5araG complex is essentially
      inactive, at least 10(5)-fold slower than the native complex. RNA cleavage by
      this analogue ribozyme is also 1000-fold slower than cleavage by either the G5dG
      or the G5dFG ribozyme, both of which lack the 2'-hydroxyl at G5. By comparison,
      catlytic efficiency of the G8araG complex as expressed by kcat/Km is comparable
      with that of the native complex and some 2 orders of magnitude more active than
      either the G8dG or the G8dFG complex.

PMID- 7524669
TI  - Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate
      proteoglycans recognized by acidic and basic fibroblast growth factor.
AB  - Recent studies have shown that fibroblast growth factors (FGFs) need to interact
      with cell-surface heparan sulfate proteoglycans (HSPGs) in order to bind to and
      activate FGF receptors. In this paper, three major heparin-binding proteins,
      histidine-rich glycoprotein (HRG) and antithrombin III (ATIII), which are
      constitutively present at high concentrations in plasma, and platelet factor 4
      (PF4), which is released locally at high concentrations by degranulating
      platelets, were tested for their ability to act as modulators of FGF activity by
      competing with the FGFs for cell-surface HSPGs. HRGs from both chicken and human,
      and human PF4, were demonstrated to compete with each other and with acidic FGF
      (aFGF) and basic FGF (bFGF) for binding to BALB/c 3T3 cell-surface HSPGs, whereas
      ATIII did not compete. Thus, HRG, PF4, aFGF, and bFGF all interact with the same
      HS chains on the 3T3 cell surface, either binding to the same or binding to
      adjacent saccharide sequences on the chains. In terms of their relative binding
      affinity for cell-surface HSPGs, the hierarchy was shown to be PF4 > or = bFGF >
      aFGF = cHRG > hHRG. HRG was also shown to significantly inhibit both FGF
      stimulated and endogenous 3T3 cell DNA synthesis. HRG also binds to extracellular
      matrices (ECM), originating from bovine corneal endothelial cells, in a heparin
      inhibitable manner. Indeed, both HRG and PF4, at physiological concentrations,
      were shown to effectively inhibit the binding of 125I-aFGF and 125I-bFGF to ECM.
      In addition, HRG was able to displace biologically active bFGF from the ECM. On
      the basis of these findings, it is proposed that HRG and PF4 may act as positive
      regulators of FGF activity by displacing FGF from the ECM or basement membrane
      and making FGF available to responsive cells. Alternatively, they could act as
      negative regulators by masking HSPGs on responsive cells and preventing FGF
      receptor activation.

PMID- 7524671
TI  - Supercoiling-regulated liquid-crystalline packaging of topologically-constrained,
      nucleosome-free DNA molecules.
AB  - Electron microscopy and circular dichroism studies of cholesteric aggregates
      derived from topologically-constrained DNA molecules indicate that the overall
      morphology and structural properties of these aggregates are fundamentally
      different from those characterizing condensed structures of nonconstrained DNA
      species. Specifically, the cholesteric pitch and twist of all hitherto
      characterized lyotropic mesophases of biopolymers--including those obtained from
      linear DNA--depend predominantly upon environmental parameters such as the
      dielectric constant of the solvent. In contrast, the properties of aggregates
      derived from closed circular supercoiled DNA are found to be solely and directly
      dictated by the superhelical density and handedness. On the basis of these
      results, as well as on the demonstrated ubiquity of liquid-crystalline DNA
      organizations in vivo, we suggest that supercoiling-regulated liquid
      crystallinity represents an effective packaging mode of nucleosome-free,
      topologically-constrained DNA molecules in living systems.

PMID- 7524666
TI  - Evolution of host cell RNA into efficient template RNA by Q beta replicase: the
      origin of RNA in untemplated reactions.
AB  - Q beta replicase can replicate a single molecule of certain species of RNA to
      10(14) copies in minutes. This replication ability has been used for in vitro
      studies of molecular evolution and is currently being utilized as a method of
      amplifying RNAs that contain probe sequences. It has been observed that Q beta
      replicase can produce replicatable RNA even in the absence of exogenously added
      template RNA. The origin of this RNA has been ascribed either to contamination
      with replicatable RNA or to an ability of Q beta replicase to synthesize RNA de
      novo from the nucleotides present in the reaction. Technologies that employ Q
      beta replicase require a thorough understanding of the conditions that lead to
      this so-called spontaneous RNA production. We have created an expression system
      and purification method with which we produce gram quantities of highly purified
      Q beta replicase, and we have identified reaction conditions that prevent the
      amplification of RNA in assays that do not contain added RNA. However, when these
      reaction conditions are relaxed, spontaneous RNA replication is seen in up to
      100% of the assays. To understand the origin of this RNA, we have cloned several
      spontaneously produced RNAs. Sequence analysis of one of these RNAs shows that it
      arose by the evolution of Escherichia coli tRNA into a replicatable template and
      not by de novo synthesis from nucleoside triphosphates in the reaction.

PMID- 7524668
TI  - Nucleic acid-binding properties of the Xenopus oocyte Y box protein mRNP3+4.
AB  - Y box proteins contain the conserved cold shock domain (CSD) and several
      basic/aromatic (B/A) islands that are rich in arginine and aromatic residues. The
      binding of purified Xenopus oocyte 6S Y box protein, mRNP3+4, to Y box RNA,
      single-stranded (ss) DNA, and double-stranded (ds) DNA was studied by gel
      mobility shift and nitrocellulose filter binding assays. mRNP3+4 specifically
      bound Y box ssDNA or RNA, while binding of dsDNA was not detected. Y box ssDNA
      and RNA did not efficiently cross-compete for mRNP3+4 binding, and no evidence
      for ternary complex formation was detected. However, Y box ssDNA binding was
      competed by high concentrations of Y box RNA or nonspecific RNA competitors,
      indicating that the ssDNA-binding site has a lower affinity for RNA. mRNP3+4
      demonstrated similar affinity for either Y box RNA or ssDNA. However, at elevated
      ionic strength RNA binding was markedly greater than ssDNA binding, indicating
      that RNA binding involves nonionic interactions that are not utilized for ssDNA
      binding. Recombinant polypeptides containing B/A islands bound Y box RNA
      exclusively, but inclusion of the CSD led to preferential ssDNA binding. The
      results demonstrate that the B/A islands are exclusively RNA-binding, while the
      CSD exhibits preferential binding of ssDNA. The inability of Y box RNA and ssDNA
      to efficiently cross-compete for mRNP3+4 binding suggests that isoforms exhibit
      preferential ssDNA or RNA binding.

PMID- 7524670
TI  - Structural analysis of N-linked oligosaccharides of equine chorionic gonadotropin
      and lutropin beta-subunits.
AB  - Equine chorionic gonadotropin (eCG) and lutropin (eLH) are composed of alpha- and
      beta-subunits with an identical amino acid sequence but show different biological
      activities. To elucidate the molecular difference between these gonadotropins,
      the structure of the N-linked oligosaccharides of each beta-subunit was
      determined. N-linked sugar chains, liberated as tritum-labeled oligosaccharides
      by hydrazinolysis followed by N-acetylation and reduction with NaB3H4, were
      neutralized by sialidase digestion and/or methanolytic desulfation. Neutralized
      oligosaccharides were fractionated by sequential chromatography on serial lectin
      affinity columns and on a Bio-Gel P-4 column. Each oligosaccharide structure was
      determined by sequential exoglycosidase digestion in conjunction with elution
      profiles on lectin columns and methylation analysis. Each beta-subunit contained
      a single N-glycosylation site, but a high degree of microheterogeneity was
      observed in the structure of its N-linked oligosaccharides. eCG beta contained
      mono-, bi-, tri-, and tetraantennary complex-type oligosaccharides in a ratio of
      3:63:13:1. eCG beta oligosaccharides contained about 16% of the bisecting GlcNAc
      and about 20% of poly-N-acetyllactosamine structures. Elongation of N
      acetyllactosamine units showed a preference to the Man alpha 1-->6 side rather
      than the Man alpha 1-->3 side. Triantennary chains had only a C-2, 4-branched
      structure. eLH beta contained only mono- and biantennary complex-type and hybrid
      type oligosaccharides in a ratio of approximately 18:67:10. eLH beta also
      contained bisected structures in about 18%. Oligosaccharides derived from the
      sulfated fraction of eLH beta contained GalNAc residues at nonreducing termini.
      Oligosaccharides from the sialylated/sulfated fraction of eLH beta contained both
      Gal and GalNAc residues at nonreducing termini, and those GalNAc residues were
      preferentially distributed to the Man alpha 1-->3 side of the trimannosyl core.
      These results clearly indicate that eCG beta and eLH beta possess structurally
      distinct N-linked oligosaccharides in addition to different charge groups even
      though they have a protein moiety identical to each other. Our results suggest
      that the biological activity of these hormones might be modulated by its terminal
      charge groups and stem structures of carbohydrate moiety synthesized in different
      organs.

PMID- 7524672
TI  - Selection of circularly permuted ribozymes from Bacillus subtilis RNAse P by
      substrate binding.
AB  - The effect of a single break in the phosphodiester backbone of Bacillus subtilis
      RNAse P RNA (P RNA) was examined using circular permutation analysis (CPA). This
      method reveals that many of the phosphodiester bonds in this catalytic RNA can be
      broken with little or no effect on substrate binding. Phosphate positions that
      show strong effects are located mostly in regions conserved among all RNAse P
      RNAs, or they are in regions known to interact directly with the pre-tRNA
      substrate. Two circularly permuted isomers of P RNA were constructed and analyzed
      in detail. The KM for both circularly permuted isomers is nearly identical to
      that of the wild-type P RNA. Since the KM of the P RNA is essentially the same as
      the binding constant to the substrate, this finding confirms the CPA results. The
      implications of backbone breakage are discussed with respect to folding and
      catalysis of the RNAse P RNA.

PMID- 7524674
TI  - A model for the stabilities of RNA hairpins based on a study of the sequence
      dependence of stability for hairpins of six nucleotides.
AB  - Thermodynamic parameters are reported for hairpin formation in 1 M NaCl by RNA
      sequences of the type GGCXUAAUYGCC, where XY is the set of 10 possible mismatch
      base pairs. A nearest neighbor analysis of the data indicates the free energy for
      loop formation at 37 C varies from 2.9 to 4.5 kcal/mol. Thermodynamic parameters
      are also reported for hairpin formation by RNA sequences of the type GGXGUAAUAYCC
      (where XY are CG, GC, AU, UA, GU, and UG), with the common naturally occurring GA
      first mismatch (45% of small and large subunit rRNA loops of six). These results
      allow the development of a model to predict the stability of RNA hairpin loops.
      The model includes the size of the loop, the identity of the closing base pair,
      the free energy increment (delta G zero 37MM) for interaction of the closing base
      pair with the first mismatch, and an additional stabilization term for GA and UU
      first mismatches. delta G zero 37L(n) = delta G zero 37i(n) + delta G zero 37MM +
      0.4 (if closed by AU or UA) -0.7 (if first mismatch is GA or UU). Here delta G
      zero 37i(n) is the free energy for initiating a loop of n nucleotides. delta G
      zero 37i(n) for n = 4-9 is 4.9, 4.4, 5.0, 5.0, 5.1, and 5.2 kcal/mol,
      respectively. The delta G zero 37MM is derived from measurements of model
      duplexes with terminal mismatches. The model gives good agreement when tested
      against four naturally occurring hairpin sequences.

PMID- 7524673
TI  - Kaliotoxin (1-37) shows structural differences with related potassium channel
      blockers.
AB  - The three-dimensional structure of kaliotoxin (1-37), KTX(1-37), a toxin from the
      scorpion Androctonus mauretanicus mauretanicus that blocks calcium-dependent
      potassium channels, has been determined by NMR. This toxin is homologous with
      other scorpion toxins such as charybdotoxin (ChTX) or iberiotoxin (IbTX) for
      which the structures are already known, but the presence of prolines in the
      expected alpha-helical region suggested that there may be some major difference
      in the structure of KTX that could be related to its different selectivity.
      Proline residues are also found in the homologous region of other scorpion toxins
      such as noxiustoxin or margatoxin. Our results indicate that KTX(1-37) contains
      the same sequence of secondary structure elements as ChTX but that the helical
      region is shorter and distorted due to the presence of two prolines. The
      distortion consists of a bending in the alpha-helix and in the presence of a
      3(10) helix turn in the last three residues. Furthermore, the increased length of
      the extended structure preceding the helix favors a different packing of this
      part of the molecule with respect to the secondary structure elements. This
      change in folding modifies the accessibility of the conserved 27Lys which is
      known, from mutation studies, to be involved in channel blocking by ChTX.

PMID- 7524675
TI  - Primer extension by various polymerases using oligonucleotide templates
      containing stereoisomeric benzo[a]pyrene-deoxyadenosine adducts.
AB  - Four isomeric benzo[a]pyrene-deoxyadenosine adducts, corresponding to the
      products of trans opening of the epoxide ring in the four configurationally
      isomeric benzo[a]pyrene dihydrodiol epoxides by the amino group of
      deoxyadenosine, were separately introduced into each of two 16-mer sequence
      contexts. The sequences were from the supF gene, and the site of the adducted
      adenine was known, for some hydrocarbon dihydrodiol epoxides, to be a hotspot for
      mutation in Context I and a coldspot for mutation in Context II. Using primers
      complementary to the 3' ends of these oligonucleotides, the abilities of several
      polymerases to replicate these templates in vitro were investigated. Each adduct
      proved to be an effective block to primer extension such that only with high
      concentrations of exo- Klenow fragment was any bypass of adducts seen. DNA
      polymerase alpha and HIV-1 reverse transcriptase were blocked 3' to the adduct
      when the configuration at C10 of the hdyrocarbon was S, and some introduction of
      thymine opposite the adenine adduct was seen with the R configuration.
      Incorporation of a nucleotide opposite the adduct occurred more readily with
      Sequenase and the Klenow fragment, and the mutagenic introduction of adenine was
      apparent in most cases. This corresponded to the A-->T transversions frequently
      seen in mutation studies with hydrocarbon dihydrodiol epoxides that react
      extensively with adenine in DNA. Overall, it was clear that sequence context,
      adduct stereochemistry, and the choice of polymerase all influenced the
      polymerization reaction. With these in vitro systems, no major differences
      correlating with the differing tumorigenicities of the isomeric dihydrodiol
      epoxides or with the hotspot or coldspot nature of the sequences were detected.

PMID- 7524676
TI  - Effect of heparin-binding growth factor-1 on bronchial healing in canine lung
      allograft transplantation.
AB  - Failure of airway healing complicates lung transplantation. Local application of
      heparin-binding growth factor-1 induces neovascularization in vivo. To determine
      the effect of direct application of heparin-binding growth factor-1 on bronchial
      healing, we performed single left lung allotransplantations in 12 dogs, and
      wrapped the bronchial anastomosis with Gelfoam impregnated with either
      recombinant heparin-binding growth factor-1 (100 micrograms, n = 6) or saline
      solution (n = 6) in a blinded fashion. After 21 days, the bronchial anastomosis
      was studied by gross examination, light and electron microscopy,
      bromodeoxyuridine uptake, measurement of bronchial breaking strength, and high
      speed computerized tomography to assess bronchial cross-sectional area and
      distensibility. The transplanted lung was examined histologically for concomitant
      lung rejection. No significant difference was found between the two groups in
      histologic bronchial healing scores, proliferation index, bronchial breaking
      strength, cross-sectional area, anastomotic distensibility, or local blood flow
      as estimated by high-speed computerized tomography scan. In the growth factor
      group, both increased neovascularization and lung rejection were found at
      histologic evaluation. We conclude that, although the use of heparin-binding
      growth factor-1 increased perianastomotic neovascularization, it did not
      contribute to improved bronchial healing, possibly because of increased lung
      rejection.

PMID- 7524677
TI  - Purification and characterization of phospholipid hydroperoxide glutathione
      peroxidase from rat testis mitochondrial membranes.
AB  - The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) is
      highly expressed in rat testis, where it is under gonadotropin control. In this
      organ a relevant PHGPx activity is strongly linked to mitochondria of cells
      undergoing differentiation to spermatozoa. This prompted a study on the possible
      difference between the soluble and the mitochondrial enzyme and the nature of the
      binding. The mitochondrial PHGPx activity could be solubilized by detergents or
      by the combined action of mild detergent treatment and ionic strength, thus
      suggesting an electrostatic binding of the protein to the inner surfaces of the
      organelle. The same chromatographic purification procedures were applied to
      cytosolic and membrane bound PHGPx, without revealing any significant difference
      between the two forms. Moreover, the electrophoretic mobility, the reactivity to
      antibodies and the fragmentation patterns also suggested the identity of the two
      forms of testis PHGPx. Eventually, testis cytosolic and membrane bound PHGPx
      showed the same substrate specificity for both peroxidic and thiol substrates. On
      the other hand, a complex behaviour on hydrophobic interaction chromatography,
      compatible with multiple forms of the enzyme, and with a different tertiary
      structure of the major peaks was observed for soluble and mitochondrial PHGPx.
      Accordingly, two-dimensional electrophoresis followed by immunostaining with
      monoclonal antibodies, showed the presence of multiple isoforms with a different
      pattern between the soluble and the mitochondrial enzyme. These differences are
      not accounted for by glycosylation or a different degree of phosphorylation of
      tyrosines. In both enzymes, indeed, no glycosylation was detected and no more
      than 10% of PHGPx molecules were shown to contain a phosphotyrosine residue.

PMID- 7524678
TI  - Expression of rat alpha-fetoprotein cDNA and its mutants in cultured mouse
      fibroblasts and identification of glycosylation sites related to electrophoretic
      variants.
AB  - Rat alpha-fetoprotein (RAFP) shows two discrete electrophoretic variants, slow
      and fast, with molecular weights of 72,500 and 69,500, respectively. To elucidate
      the structural basis of this heterogeneity, we developed the expression system of
      RAFP cDNA and its mutants with the use of cultured mouse fibroblasts and a
      retrovirus vector. This produced recombinant wild-type and three mutant proteins
      and has several advantages over the use of Escherichia coli or Saccharomyces
      cerevisiae. The mutants were designed to lack either one or both of the two
      possible glycosylation sites on RAFP. Electrophoretic analyses relating to the
      glycosylation states of the recombinant proteins as well as of natural RAFP
      produced by rat cells before and after digestion with glycopeptidase F indicated
      that the slow variant has carbohydrate units located at Asn-93 and Asn-229 and
      the fast one has one at Asn-229.

PMID- 7524680
TI  - pH titration of the histidine residues of cyclophilin and FK506 binding protein
      in the absence and presence of immunosuppressant ligands.
AB  - Histidine residues in immunophilins, particularly His-126 of cyclophilin (CyP)
      and His-87 of the FK506 binding protein (FKBP), have been suggested to play
      important roles in ligand binding and peptidyl prolyl cis-trans isomerase
      (PPiase) catalysis. The charged states of the histidine residues in FKBP and CyP,
      which were characterized by their pKa values, have been determined in the absence
      and presence of the immunosuppressant ligands, ascomycin and cyclosporin A (CsA),
      respectively, by using a heteronuclear two-dimensional NMR method. Overall, the
      histidine residues in FKBP and CyP are very acidic with pKa values ranging from <
      or = 2.8 to 6.5, indicating that they are predominantly uncharged at
      physiological pH. To our knowledge, the pKa value of < or = 2.8 determined from
      this study is the lowest pKa reported for the free imidazole ring of the
      histidine residues in proteins. The abnormally acidic pKa's of His-25 in FKBP and
      His-54 in CyP could be explained by their highly positively charged environments.
      His-87 of FKBP, which is located in the FK506 binding pocket, was found to exist
      in two forms in free FKBP with pKa values of 5.9 and 6.5 for the major and minor
      forms, respectively. His-126, which is part of the CsA and substrate binding
      site, has a pKa of 6.3 in free CyP. The pKa values of these two histidine
      residues in the free proteins are higher than the pKa's obtained for the peptidyl
      prolyl cis-trans isomerase (PPiase) activity of these enzymes, indicating that
      the acid/base characters of His-87 of FKBP and His-126 of CyP are not essential
      in the PPiase catalysis. The hydrogen bonding of the histidine imidazole rings
      and the effect of hydrophobicity upon changes in pKa values are discussed.

PMID- 7524679
TI  - Human cysteine dioxygenase type I: primary structure derived from base sequencing
      of cDNA.
AB  - The base sequence of cDNA encoding the complete human liver cysteine dioxygenase
      type I (CDO-I; EC 1.13.11.20) message, and the derived amino-acid sequence are
      reported. CDO-I is encoded on a single mRNA species (approx. 1.5 kb). Human CDO-I
      clones were identified by screening a liver cDNA library, and inserts were
      isolated and sequenced. In addition, human liver total RNA was reverse
      transcribed and CDO-I cDNA amplified by PCR using a modified poly-T primer and
      specific CDO-I primers to give a second source of sequencing template. The CDO-I
      message encodes a 200 amino-acid residue protein, the sequence of which has
      greater than 90% homology with the equivalent rat enzyme. The message was not
      expressed in a human hepatoma cell line (Hep G2).

PMID- 7524681
TI  - Analysis of aggrecan and tenascin gene expression in mouse skeletal tissues by
      northern and in situ hybridization using species specific cDNA probes.
AB  - Cartilage matrix is an interacting multicomponent system of collagen fibrils,
      fibril-associated small proteoglycans, and large proteoglycans and glycoproteins
      entrapped within the fibrillar network. In order to better understand the
      relationships between these different components we have constructed short cDNA
      clones for detection of mRNAs for two major noncollagenous macromolecules of
      cartilage matrix, aggrecan and tenascin. We subsequently determined their
      corresponding mRNA levels by Northern analysis in a panel of total RNAs isolated
      from several newborn mouse tissues. The expression of aggrecan was strictly
      restricted to cartilages while tenascin mRNA was present at variable levels in
      most of the tissues studied. The cDNA clones were also used to identify the cells
      responsible for aggrecan and tenascin production in newborn mouse tissues by in
      situ hybridization. With this technique aggrecan mRNA was detected in
      chondrocytes throughout the developing skeleton in a pattern very similar but not
      identical to those of type II and IX collagen mRNAs. In the newborn mouse
      skeleton tenascin and aggrecan mRNAs were expressed essentially in a mutually
      exclusive manner, tenascin transcripts being present in osteoblasts, periosteal
      and perichondrial cells, and in cells at articular surfaces. None of these cells
      expressed the cartilage specific collagen or aggrecan genes. The results further
      suggest different patterns of gene expression in chondrocytes based on their
      location in the different cartilages.

PMID- 7524683
TI  - Characterization of the three different states of the cholecystokinin (CCK)
      receptor in pancreatic acini.
AB  - By measuring binding of [125I]CCK-8 and [3H]L-364,718 to rat pancreatic acini we
      demonstrated directly that the pancreatic CCK receptor can exist in three
      different affinity states with respect to CCK--high affinity, low affinity and
      very low affinity. Binding of [125I]CCK-8 reflects interaction of the tracer with
      the high and low affinity states, whereas binding of [3H]L-364,718 reflects
      interaction of the tracer with the low and very low affinity states. Treating
      acini with carbachol abolished the high affinity state of the CCK receptor and
      converted approximately 25% of the low affinity receptors to the very low
      affinity state. Carbachol treatment was particularly useful in establishing the
      values of Kd for the high and low affinity states for different CCK receptor
      agonists and antagonists. Of the various CCK receptor agonists tested, CCK-8 had
      the highest affinity for the high affinity state (Kd approximately 1 nM), whereas
      CCK-JMV-180 had the highest affinity for the low (Kd 7 nM) and very low affinity
      (Kd 200 nM) states. Gastrin and de(SO4)CCK-8 had affinities for the high and low
      affinity states of the receptor that were 100- to 400-fold less than those of CCK
      8 but had affinities for the very low affinity state that were only 3- to 10-fold
      less than that of CCK-8. CCK receptor antagonists showed several patterns in
      interacting with the different states of the CCK receptor. L-364,718 had the same
      affinity for each state of the CCK receptor. CR1409 and Bt2cGMP each had similar
      affinities for the high and low affinity states and lower affinity for the very
      low affinity state. L-365,260 and CCK-JMV-179 had the highest affinity for the
      low affinity state and lower affinities for the high and very low affinity
      states. Different CCK receptor agonists caused the same maximal stimulation of
      amylase secretion but showed different degrees of amplification in terms of the
      relationship between their abilities to stimulate amylase secretion and their
      abilities to occupy the low affinity state of the CCK receptor. When
      amplification was expressed quantitatively as the value of Kd for the low
      affinity state divided by the corresponding EC50 for stimulating amylase
      secretion the values were CCK-8 (1000), de(SO)CCK-8 (1500), gastrin (100) and CCK
      JMV-180 (Menozzi, D., Vinayek, R., Jensen, R.T. and Gardner, J.D. (1991) J. Biol.
      Chem. 266, 10385-1091).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7524685
TI  - Altered interaction of human granulation-tissue fibroblasts with fibronectin is
      regulated by alpha 5 beta 1 integrin.
AB  - Granulation-tissue fibroblasts express an unique phenotype distinct from normal
      fibroblasts. Due to the importance of the cell-matrix interactions in the
      regulation of cell morphology and behavior, we have compared the cell adhesion
      apparatus, especially integrin-type receptors, in fibroblasts cultured from
      healthy human periodontal connective tissues and from chronic and wound
      granulation tissues. The spreading of granulation-tissue cells on fibronectin,
      but not on type I collagen or laminin, was slower when compared with the normal
      fibroblasts. Cell spreading on fibronectin could be inhibited by RGD-containing
      peptide, suggesting integrin-mediated interaction. Both cell types expressed beta
      1 integrin subunit, which associated with several integrin alpha subunits, namely
      alpha 1, alpha 2, alpha 3, alpha 5 and alpha v. In addition to beta 1 subunit,
      alpha v chain formed heterodimers with beta 3 and beta 5 subunits. Thus, these
      cells have multiple putative fibronectin, laminin, collagen, and vitronectin
      receptors. Cell spreading of both cell types on fibronectin was inhibited with
      anti-beta 1 and anti-alpha 5 antibodies, but antibodies against other putative FN
      binding integrins (alpha 3, alpha v, and alpha v beta 3) had no effects.
      Furthermore, granulation-tissue fibroblasts showed delayed spreading on
      substrates coated with anti-beta 1 or anti-alpha 5 integrin antibodies. On
      substrates coated with anti-alpha 3 antibody, both cell types spread equally
      well. By FACS analysis, the amount of beta 1 and alpha 5 integrin subunits
      expressed on the cell surfaces was slightly elevated in GTFs compared with HGFs.
      Thus, the findings in this study indicate that the weakened interaction of
      granulation-tissue fibroblasts with fibronectin is regulated by altered function
      of alpha 5 beta 1 integrin.

PMID- 7524682
TI  - LDL and acetyl-LDL inhibit the NK activity and are taken up by CD56+ lymphocytes.
AB  - The effect of LDL and modified LDL (acetyl-LDL) was studied on human natural
      killer cell-mediated cytotoxicity against K562 cells. Incubation for 24 h of
      peripheral blood lymphocytes (PBL) with a high concentration (200 micrograms/ml)
      of LDL decreased the NK activity in some donors. After acetylation of the LDL
      protein (apoB), the modified-LDL systematically inhibited the NK function of PBL
      in a time- and dose-dependent manner. Inhibition mediated by acetyl-LDL (AcLDL)
      was significantly greater than that of LDL, indicating that the apoB modification
      can mediate the inhibition of the NK function. AcLDL also inhibited the NK
      activity of peripheral blood mononuclear cells, suggesting that, under our
      experimental conditions, monocytes are not efficient enough to protect NK cells
      against the adverse effects of modified-LDL. With a cytofluorimetric analysis,
      the internalization of acetyl-LDL by PBL was demonstrated and was only 3-4 times
      lower than LDL internalization in lymphocytes. It appeared to be time,
      temperature and dose dependent, saturable and different from the internalization
      mediated by the known scavenger receptors. Finally, CD14- CD3+ lymphocytes and
      CD14- CD56+ lymphocytes were able to internalize AcLDL in the same way. Our
      results suggest that in some in vivo circumstances, when the LDL concentration
      and/or the modified-LDL/LDL ratio increase in tissues, lipoproteins are
      internalized by NK cells and also can induce adverse effects on the NK function.

PMID- 7524684
TI  - Effects of cholecystokinin (CCK) and other secretagogues on isoforms of protein
      kinase C (PKC) in pancreatic acini.
AB  - We used rat pancreatic acini and measured the effects of various agents on
      digestive enzyme secretion, diacylglycerol (DAG) and the cellular distribution of
      protein kinase C (PKC) enzyme activity as well as isoforms of PKC determined by
      quantitative immunoblot analysis. TPA, but not CCK-8, caused translocation of PKC
      enzyme activity from the cytosol fraction to the membrane fraction. Immunoblot
      analysis detected PKC-alpha, PKC-delta, PKC-epsilon and PKC-zeta. PKC-beta, PKC
      gamma and PKC-eta were not detected. TPA caused translocation of all isoforms
      from cytosol to membrane, whereas CCK-8 caused translocation of PKC-delta and PKC
      epsilon, carbachol caused translocation of PKC-epsilon, and bombesin and secretin
      caused no detectable translocation of any isoform. Specific receptor antagonists
      could prevent, as well as reverse completely, the translocation of PKC isoforms
      caused by CCK-8 or carbachol. Agonists added in sequence with an interposed
      addition of a specific receptor antagonist caused cycling of PKC-epsilon between
      cytosol and membrane fractions. Each receptor-mediated agonist that caused
      translocation of PKC also increased DAG, and with CCK-8 and carbachol cycling of
      PKC-epsilon between cytosol and membrane was accompanied by corresponding cyclic
      changes in cellular DAG. CCK-JMV-180, bombesin and secretin increased DAG but did
      not cause translocation of any PKC isoform. Translocation of a PKC isoform could
      be accounted for by whether the increased DAG originated from PIP2 (accompanied
      by translocation) or from phosphatidylcholine (no accompanying translocation).
      Thus it appeared that DAG, in pancreatic acini, is functionally compartmentalized
      depending on the source of the lipid. Studies using CCK-8 and CCK-JMV-180
      indicated that occupation of the low affinity state of the CCK receptor by either
      peptide increased DAG from phosphatidylcholine, whereas occupation of the very
      low affinity state by CCK-8 increased DAG from PIP2 and caused translocation of
      PKC-delta and PKC-epsilon. TPA stimulated amylase secretion, indicating that
      activation of PKC can stimulate enzyme secretion; however, with the various
      receptor-mediated secretagogues there was no consistent, unequivocal correlation
      between translocation of an isoform of PKC and accompanying changes in enzyme
      secretion.

PMID- 7524686
TI  - Glycosylation of synthetic T helper cell epitopic peptides influences their
      antigenic potency and conformation in a sugar location-specific manner.
AB  - The immunodominant T helper cell epitopes 31D and VF13N of rabies virus
      nucleoprotein and glycoprotein, respectively, correspond to peptide sequences
      AVYTRIMMNGGRLKR and VVEDEGCTNLSGF, and are expressed between amino acids 404-418
      and 29-41, of the appropriate proteins. We investigated how internal or external
      glycosylation affects the biological activity and conformation of the peptides
      31D and VF13N. Mid-chain incorporation of maltobiose or N-acetylglucosamine
      moieties into the asparagine residues greatly diminished the T-cell stimulatory
      activity in vitro (due to the diminished ability of the glycopeptides to bind to
      major histocompatibility complex determinants) and reduced the characteristic
      alpha-helicity of the peptides in aqueous trifluoroethanol solutions. In
      contrast, addition of maltobiose- or N-acetylglucosamine-coupled asparagines to
      the N-termini of peptides 31D and VF13N resulted in unchanged T-cell activity.
      Furthermore, N-terminal glycosylation of peptide 31D, as indicated by the
      functional assay, decreased the sensitivity of the peptide to degradation in
      human serum and did not affect the alpha-helical conformation. These data
      indicate that glycosylation of T-cell epitopes is not a preferable method for the
      preparation of antagonists, but incorporation of the sugars to appropriate
      positions may be advantageous in the design of T-cell agonists and peptide-based
      vaccines.

PMID- 7524688
TI  - Site-specific religation of G-CSF fragments through a thioether bond.
AB  - A new approach is described for linking, through a thioether bond, the C-terminus
      of one unprotected polypeptide with the N-terminus of another. Homocysteine
      thiolactone is attached to the C-terminus of one polypeptide by reverse
      proteolysis and provides through hydroxylamine treatment a free sulfhydryl group.
      The alpha-amino group of a second polypeptide is selectively iodoacetylated by
      reaction with iodoacetic anhydride at pH 6.0 or the N-hydroxysuccinimide ester
      derivative at pH 7.0. Coupling of the two modified fragments occurs in a
      spontaneous alkylation reaction under mild conditions. After preliminary
      experiments with small peptides, this approach was extended to large protein
      fragments derived from recombinant analogs of G-CSF by enzymatic digestion. This
      approach provides a means of making head-to-tail protein chimeras or introducing
      noncoded structural elements into a protein.

PMID- 7524687
TI  - DNA-linked RNase H for site-selective cleavage of RNA.
AB  - ADNA-linked RNase H (Hybrid Enz-1) (Kanaya et al. (1992) J. Biol. Chem. 267, 8492
      8498), in which dGTCATCTCC was attached to E. coli RNase H via a covalent linker
      of 21 A, was altered to improve the site-specific RNA cleavage by increasing the
      linker length. The sizes of the linkers on these hybrid enzymes (Hybrid Enz-2, 
      3, and -4) differed by 3 A, the axial rise of the DNA/RNA hybrid, to give 18-, 24
      , and 27-A lengths. The conjugate with a size of A was able to cleave a synthetic
      22mer RNA (5'-rAAGAUGUCUACGGAGAUGACCA-3'), containing the complementary 9mer RNA
      sequence (underlined), at one position, A16-U17. The kinetic parameters of Hybrid
      Enz-1, -2, -3, and -4 were examined using a 9mer RNA target. The results showed
      that longer linkers produced higher Km, kcat, and kcat/Km values, and the kcat/Km
      value of the conjugate with the 27-A linker reached 83% of that of the wild-type
      RNase H. Hybrid Enz-4 was found to be useful as an RNA restriction endonuclease.

PMID- 7524689
TI  - Biotinylated hyaluronic acid: a new tool for probing hyaluronate-receptor
      interactions.
AB  - Hyaluronic acid (HA) is a linear polysaccharide composed of repeating
      disaccharide units of D-glucuronic acid (GlcUA) and N-acetyl-D-glucosamine
      (GlcNAc). Hyaluronate plays an important role in many biological processes as
      mediated by its interactions with a number of HA-binding proteins (the
      "hyaladherins") and with the cell surface HA-receptor, CD44. Studies of
      hyaluronate-hyaladherin interactions would be greatly facilitated by the
      availability of molecular probes derived from HA. We recently reported a
      convenient chemical modification of hyaluronate that introduces multiple pendant
      amine functionalities onto the HA carboxylate residues. We now report the
      preparation of biotinylated hyaluronic acid (molecular weight = 1.2 x 10(6) Da)
      as a probe for histochemical and immunochemical characterization of HA-binding
      proteins. Approximately one-third of the available HA glucuronate residues could
      be readily biotinylated in high molecular weight HA.

PMID- 7524690
TI  - Displaying radiologic images on personal computers: practical applications and
      uses.
AB  - This is the fifth and final article in our series for radiologists and imaging
      scientists on displaying, manipulating, and analyzing radiologic images on
      personal computers (PCs). There are many methods of transferring radiologic
      images into a PC, including transfer over a network, transfer from an imaging
      modality storage archive, using a frame grabber in the image display console, and
      digitizing a radiograph or 35-mm slide. Depending on the transfer method, the
      image file may be an extended gray-scale contrast, 16-bit raster file or an 8-bit
      PC graphics file. On the PC, the image can be viewed, analyzed, enhanced, and
      annotated. Some specific uses and applications include making 35-mm slides,
      printing images for publication, making posters and handouts, facsimile (fax)
      transmission to referring clinicians, converting radiologic images into medical
      illustrations, creating a digital teaching file, and using a network to
      disseminate teaching material. We are distributing a 16-bit image display and
      analysis program for Macintosh computers, Dr Razz, that illustrates many of the
      principles discussed in this review series. The program is available for no
      charge by anonymous file transfer protocol (ftp).

PMID- 7524692
TI  - Diagnosis of polyomavirus-induced hepatic necrosis in psittacine birds using DNA
      probes.
AB  - Liver sections from 32 psittacine birds with multifocal to coalescing
      hepatocellular necrosis were examined to determine the cause of disease. Avian
      polyomavirus (APV) infection (19 of 32 birds), bacterial hepatitis (5 of 32
      birds), and chlamydiosis (3 of 32 birds) were major causes of hepatic disease.
      The presence of APV inclusions or nucleic acid was demonstrated using hematoxylin
      and eosin (HE) staining, DNA in situ hybridization, and DNA amplification with
      Southern blotting. Amphophilic intranuclear inclusions, suggestive of APV
      infection, were observed in HE-stained liver sections from 5 of 32 birds.
      Hepatocellular karyomegaly was present in liver tissues from 10 birds (5 birds
      with typical APV inclusions and 5 birds without discernable inclusions). DNA in
      situ hybridization recognized intranuclear APV nucleic acid in liver sections of
      18 of 32 birds. DNA amplification with Southern or dot blots also identified APV
      nucleic acid in processed, paraffin-embedded livers of 18 of 32 birds. This study
      demonstrates that acute APV infection is a frequent cause of multifocal to
      coalescing hepatocellular necrosis in psittacine birds. Furthermore, APV
      infection is best diagnosed using DNA probes, especially when typical
      intranuclear inclusions are not observed microscopically.

PMID- 7524691
TI  - Effect of fetal striatal and astrocyte transplants into unilateral excitotoxin
      lesioned striatum.
AB  - Studies have suggested that neurotrophic mechanisms may underlie transplant
      induced functional recovery. Astrocytes have been reported to be a source of
      neurotrophic factors. The present study examined the possible role of cultured
      astrocytes in promoting recovery of apomorphine-induced rotation behavior in rats
      with unilateral kainic acid (KA) lesions of the striatum. Five weeks after the
      lesions, one group of rats received fetal striatal tissue (E17) transplants,
      another group received transplants of cultured astrocyte suspension, and the
      remaining rats received sham transplants and served as controls. Apomorphine
      induced rotation behavior was tested 4 weeks after the KA lesions, and 5 and 10
      weeks following the transplantation. The KA-induced rotation behavior was reduced
      by the striatal transplants but not by the cultured astrocyte transplants 5 and
      10 weeks following the transplantation. Histochemical analysis indicated that the
      striatal transplants had survived and grown and contained neurons and glia with
      similar morphology to those in the host brain. Immunocytochemical analysis of the
      astrocyte transplant sites revealed heavy glial fibrillary acidic protein and OX
      42 staining in the transplant areas, suggesting that the transplanted astrocytes
      may have survived in the host brain. Although fetal striatal transplants can
      ameliorate apomorphine-induced rotation behavior, transplants of astrocytes alone
      may not be sufficient to reverse the functional deficits produced by KA lesions.

PMID- 7524693
TI  - [Serum pancreatic enzymes in patients with chronic renal failure on hemodialysis
      and in transplant patients].
AB  - OBJECTIVE: The aim of this study was to evaluate which of serum pancreatic
      enzymes was less influenced by chronic renal failure (CRF). MATERIALS AND
      METHODS: 40 patients with CRF undergoing hemodialysis (A group) and 24 renal
      transplant patients (B group) were considered. None of these patients showed
      clinical and instrumental findings of exocrine pancreas disease. Total amylase (T
      Amy), pancreatic isoamylase (P Amy), lipase (L) and Elastase-1 (E-1) were
      measured (in A group immediately before hemodialysis). RESULTS: In A group T Amy
      and P Amy showed a significant correlation with serum creatinine level. In A
      group T Amy serum levels were increased in 65% of cases, P Amy in 72.5%, L in
      47.5%, E-1 in 10%; in B group T Amy serum levels were increased in 41.6%, P Amy
      in 20.1%, L in 8.3% and E-1 in 4.1%. Statistical comparison showed a
      significantly lower percentages in B group considering P Amy (p < 0.001) and L (p
      = 0.003). CONCLUSIONS: Our data suggest that E-1 is the only pancreatic enzyme
      whose specificity is not limited by CRF and thereby may be of value in the
      diagnosis of the exocrine pancreatic disease in patients with CRF on
      hemodialysis.

PMID- 7524695
TI  - Identification of an epitope of tumor necrosis factor (TNF)-receptor type 1 (p55)
      recognized by a TNF-alpha-antagonist monoclonal antibody.
AB  - The relationships between epitope topography and agonistic/antagonistic effects
      of anti-TNF receptor type 1 (TNF-R1) antibodies on TNF-alpha cytotoxic activity
      have been studied. To this purpose various monoclonal antibodies (mAbs) against
      the soluble form of TNF-R1 (sTNF-R1) have been generated and characterized.
      Epitope topography studies identified at least four distinct epitopes located
      outside (4E10) or within (or close to) the TNF-alpha binding site of urinary sTNF
      R1 (7H3, 4C1, 9B11). mAbs 7H3 and 4C1 were able to neutralize the inhibition of
      human TNF-alpha cytotoxicity on L-M cells by sTNF-R1, while 4E10 was unable.
      Moreover, 7H3 and 4C1 were able to antagonize the TNF-alpha cytotoxicity on human
      U937 cells, while they were uneffective on mouse L-M cells, suggesting that these
      antibodies recognize, in a species-specific mode, also the membrane form of the
      human receptor. No agonistic effects were observed when these antibodies were
      used in the absence of TNF-alpha. Epitope topography studies carried out using
      overlapping decapeptides covering most of the sTNF-R1 sequence showed that
      residues 143-148 of the fourth cysteine-rich domain of the receptor (FFLREN)
      contain antigenic determinants recognized by the antagonist antibody 7H3. These
      results suggest that at least part of residues 143-148 of sTNF-R1 are surface
      exposed on the soluble as well as on the membrane forms of TNF-R1 and are
      accessible to TNF-alpha antagonists.

PMID- 7524696
TI  - Pentagastrin infusions in patients with panic disorder. II. Neuroendocrinology.
AB  - Cholecystokinin (CCK) has well-documented anxiogenic effects in animals and
      normal people, and panicogenic effects in patients with panic disorder, but
      little is known about its neuroendocrine profile. We examined neuroendocrine
      responses to intravenous infusions of pentagastrin, a selective CCK-B receptor
      agonist, in 10 patients with panic disorder and 10 normal control subjects.
      Pentagastrin potently activated the hypothalamic-pituitary-adrenal (HPA) axis,
      but did not release growth hormone or any of several vasoactive peptides
      (neurokinin A, substance P, vasoactive intestinal peptide). The HPA axis response
      was unrelated to increases in symptoms. Panic patients did not differ from
      controls in neuroendocrine responses to the CCK agonist. Differential sensitivity
      to novelty stress accounted for the only patient-control differences in
      neuroendocrine profiles. The data suggest that CCK may help modulate normal HPA
      axis activity, but its anxiogenic effects are unrelated to its stimulatory
      effects on the HPA axis. Pentagastrin provides a safe and readily available probe
      for further study of CCK receptor systems in humans.

PMID- 7524694
TI  - Canine acute phase response: relationship between serum cytokine activity and
      acute phase protein in dogs.
AB  - The changes in serum activity of interleukin (IL)-1, IL-6, and tumor necrosis
      factor (TNF) were studied in dogs with acute inflammation. Dogs with local
      inflammation induced by an intramuscular injection of turpentine oil showed
      clinically a typical progression in the inflammatory response, recovering on day
      14 after the treatment. Serum concentrations of C-reactive protein (CRP) and
      alpha 1 acid glycoprotein (alpha 1AG) increased, and the albumin concentration
      decreased in all dogs during the acute phase response. These values each returned
      to the normal range from day 14 to 21. Serum IL-6-like activity was detected from
      2 hr to day 6 after treatment. Serum TNF-like activity in the treatment group was
      detected at a low level from 3 to 24 hr after treatment, but there was no
      statistically significant difference compared with the control group. The
      temporal changes in serum IL-6 and TNF-like activities preceded those in serum
      concentrations of CRP, alpha 1 AG, and albumin. No dogs showed a detectable rise
      in serum IL-1-like activity after treatment.

PMID- 7524698
TI  - Insulin-like growth factor binding proteins show distinct patterns of expression
      in the rat uterus.
AB  - An intrinsic insulin-like growth factor (IGF) system, complete with IGF ligands,
      receptors, and biological responses, is present in the rat uterus, where it is
      thought to regulate uterine homeostasis by autocrine/paracrine mechanisms. It is
      known that IGF binding proteins (IGFBP) modulate IGF-I and IGF-II action, but
      very little information is available concerning their cellular localization in
      the uterus. Therefore, we have employed in situ hybridization to localize IGFBP
      1, -2, -3, -4, -5, and -6 mRNAs in the adult rat uterus during the estrous cycle.
      IGFBP-1 was undetectable in all uteri examined. IGFBP-2 mRNA was localized only
      in the luminal epithelium of the endometrium. It was abundant during proestrus
      (P1000 h, P2000 h) and early estrus (E0200 h), but was relatively low at other
      stages of the cycle. IGFBP-3 mRNA was localized to the stroma cells juxtaposed to
      the endometrium. A weak signal was detected on estrus morning (E0200 h, E1000 h),
      but high levels of IGFBP-3 mRNA were observed in the stroma cells on Day 12 of
      pregnancy. IGFBP-4 mRNA was localized only in the luminal epithelium of the
      endometrium. It was moderately abundant at diestrus I and II, but the signal was
      very low or absent at other times in the cycle. IGFBP-5 mRNA was localized in the
      circular and longitudinal muscle layers of the myometrium. The IGFBP-5
      hybridization signal was maximal at diestrus, weak on proestrus, and moderate
      during estrus. IGFBP-6 mRNA was also expressed in the myometrium. The signal was
      strong on estrus morning (E0200 h and E1000 h) and low or absent at other times
      in the cycle. These results provide the first direct evidence that the genes
      encoding the six IGFBP are expressed in a tissue-specific manner in the adult rat
      uterus. Equally important, the levels of the mRNA for each IGFBP appear to change
      throughout the estrous cycle, but not in a parallel fashion. These results
      support the hypothesis that inducible and tissue-specific expression of IGFBP-2
      to -6 may be involved in modulating the activity of the IGF ligands during the
      proliferative and secretory phases of the uterine cycle.

PMID- 7524697
TI  - Identification of mouse ZP3 protein in mammalian oocytes with antisera against
      synthetic ZP3 peptides.
AB  - The mouse zona pellucida (ZP) protein ZP3 plays an important role in the process
      of fertilization by mediating sperm binding and the acrosome reaction. ZP3
      primary structures are highly conserved, as revealed by cDNA cloning. We raised
      antisera against synthetic peptides that are either conserved in the structure of
      ZP3 from different mammalian species (AS ZP3-5 and AS ZP3-6) or specific for
      mouse ZP3 (AS ZP3-2). In ovary sections, AS ZP3-2 revealed immunoreactivity only
      to mouse ZP. AS ZP3-5 and AS ZP3-6 reacted with mouse, human, rat, hamster,
      porcine, and bovine ZP proteins. In porcine oocytes, immunoreactive material was
      highly abundant in the ooplasm. Immunoblots showed that antiserum AS ZP3-5
      recognized the mouse ZP3 protein. In porcine ZP preparations, AS ZP3-5 recognized
      a 53-kDa ZP protein. No reaction was observed with purified porcine ZP3 alpha or
      with ZP3 beta. Immunofluorescence studies revealed that AS ZP3-5 and AS ZP3-6
      antibodies react with ZP of isolated porcine and human oocytes. Our results show
      that antisera against synthetic mouse ZP3 peptides can be used as markers for the
      identification of ZP3-like proteins in mammalian oocytes and might be useful
      tools for the evaluation of ZP integrity and ZP3 function.

PMID- 7524699
TI  - Interleukin-1 beta stimulates nitrite production in the rat ovary: evidence for
      heterologous cell-cell interaction and for insulin-mediated regulation of the
      inducible isoform of nitric oxide synthase.
AB  - Recent studies suggest that endogenously generated nitric oxide (NO) may mediate
      the effects of cytokines in a variety of tissues. In an effort to determine
      whether NO generation mediates any of the intraovarian actions of interleukin-1
      beta (IL-1 beta), we have looked for and characterized the accumulation of
      nitrite by IL-1 beta-treated, cultured whole ovarian dispersates. Application of
      IL-1 beta significantly enhanced basal nitrite release in a dose-, cell density-
      and time-dependent manner, the latter characterized by a lag time of about 20 h,
      suggestive of induction of NO synthase (NOS). Cellular NOS activity was also
      elevated by IL-1 beta. Sustained nitrite accumulation required continuous
      application of IL-1 beta. The maximally stimulating dose of IL-1 beta (50 ng/ml)
      produced a 10-fold increase in nitrite accumulation by 96 h of culture, an effect
      reduced 23% when cells were cultured in substrate (i.e., arginine)-free media. IL
      1 beta-stimulated nitrite accumulation was reduced to control levels by the
      simultaneous application of an IL-1 beta receptor antagonist, thereby suggesting
      a specific receptor-mediated effect. Both the control and IL-1 beta-stimulated
      levels of nitrite accumulation were attenuated in a dose-dependent manner by
      inhibitors that favor the inducible form of NOS. In contrast, selective
      inhibitors of the constitutive form of NOS were significantly less potent. No
      inhibition was noted after application of an inactive stereoisomeric analogue. IL
      1 beta-induced nitrite accumulation was shown to require cell-cell interaction
      between granulosa and theca-interstitial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524701
TI  - Thyroglobulin-specific T cell line from a healthy individual does not produce
      proinflammatory cytokines on antigenic stimulation: an implication for possible
      fail-safe mechanism to avoid autoimmunity.
AB  - In order to investigate the regulation of autoimmune response to thyroglobulin
      (Tg), one of the thyroid autoantigens, we established a Tg-specific T cell line
      by stimulation of peripheral blood mononuclear cells from a healthy volunteer
      with Tg and characterized its cytokine production pattern. The Tg-specific T cell
      line, designated DH5D1, obtained from a limiting dilution culture bore alpha beta
      T cell receptor and was CD4 and CD45RO positive. Upon stimulation with Tg, DH5D1
      secreted little or no titers of IL-2, TNF-alpha, and IFN-gamma, whereas
      activation with combination of phorbol myristate acetate and calcium ionophore
      produced measurable levels of these cytokines. These results indicate that the Tg
      specific T cell line is not defective in its capacity to produce proinflammatory
      cytokines and suggest that the inability of cytokine production by autoreactive T
      cells of healthy individuals is one fail-safe mechanism for preventing aggression
      of harmful autoimmune response.

PMID- 7524700
TI  - Cloning and characterisation of TPO autoantibodies using combinatorial phage
      display libraries.
AB  - Thyroid lymphocyte RNA from a Hashimoto patient with high serum levels of
      autoantibodies to thyroid peroxidase (TPO) was used to construct a phage display
      antibody library in the phagemid vector pComb3. The library (100,000cfu) encoded
      IgG1 heavy chains together with kappa light chains. Selection of the phages
      displaying TPO antibody on TPO-coated ELISA plates yielded a phage population
      enriched for surface expression of TPO antibody Fabs. 3 different Fabs specific
      for TPO were subsequently isolated with affinities in the region of 10(9) molar
      1. 2 of the Fabs recognised the same, or closely related, epitopes on TPO whereas
      the third Fab recognised a different epitope. These 2 epitopes were recognised by
      TPO autoantibodies in the serum of the lymphocyte donor and a series of 10
      patient sera. Available sequence data showed that several non-self antibodies and
      non-thyroid autoantibodies use the same V kappa and VH germline genes as TPO
      autoantibodies. There appeared to be no clear relationship between gene sequence
      or gene family usage by TPO autoantibodies of the same or similar epitope
      specificity.

PMID- 7524703
TI  - B cell number and function in Graves' disease.

PMID- 7524702
TI  - Adhesion and cytotoxicity of myelin basic protein-specific encephalitogenic T
      cells to normal and inflamed cerebral endothelial cells.
AB  - To study the mechanisms involved in the pathogenesis of the blood-brain barrier
      (BBB) breakdown in autoimmune demyelinating diseases, such as experimental
      allergic encephalomyelitis (EAE), we investigated the cell interaction in vitro
      between myelin basic protein (MBP)-specific encephalitogenic T cells and normal
      and inflamed cerebral endothelial cells, and the cytotoxic effect of antigen
      specific T cell lines on normal and inflamed cerebral endothelial cells. The
      importance of relationship between cell surface adhesion and cytotoxic T
      lymphocyte (CTL) was examined by monoclonal antibodies (mAb) against adhesion
      receptors. The adhesion of encephalitogenic T cells to inflamed endothelial cells
      was significantly increased as compared with normal endothelial cells (P <
      0.001). The percentage lysis of inflamed endothelial target cells was
      significantly increased by incubation with MBP-encephalitogenic T cell lines in
      the presence of MBP as compared with those of normal endothelial targets (P <
      0.0001). Intercellular adhesion molecule-1 (ICAM-1) is not involved in T cell
      adhesion to endothelial cells or cytotoxic endothelial cell lysis. Antibodies
      against human alpha 4 integrin (HP 2/1) and beta 1 (A11B2) inhibited T cell
      adhesion, but did not block cytotoxic endothelial cell lysis. These results
      indicate that T cell adhesion to inflamed cerebral endothelial cells and
      cytotoxicity of T cells for cerebral endothelial cells may play a central role in
      the breakdown of the BBB and development of inflammatory lesions in the central
      nervous system(CNS).

PMID- 7524704
TI  - Bcl-2 and Fas, molecules which influence apoptosis. A possible role in systemic
      lupus erythematosus?
AB  - Polyclonal B cell activation and the production of antibodies against a variety
      of autoantigens are features of systemic lupus erythematosus (SLE). Autoreactive
      B cells are found in healthy individuals but their numbers are probably regulated
      by cell death, after a few days, in the absence of proliferative stimuli. The
      process which achieves this regulation is known as apoptosis or programmed cell
      death. It has been postulated that in SLE patients dysfunction of apoptosis could
      result in the inappropriate longevity of autoreactive B cells, allowing
      autoantibody levels to reach pathogenic thresholds. This hypothesis has arisen as
      a result of studies revealing links between autoimmunity and two molecules which
      influence apoptosis. These are bcl-2 which enhances cell survival by inhibiting
      or delaying apoptosis and Fas, a cell surface molecule involved in the induction
      of apoptosis. Transgenic mice over expressing bcl-2 in their B cells showed
      polyclonal B cell expansion and their B cells showed extended survival in vitro.
      After a few months these mice developed an autoimmune syndrome resembling SLE.
      Mice that carry the lpr disorder have defects in the Fas gene. These mice, which
      do not express functional Fas molecules, suffer from an SLE-like autoimmune
      syndrome. Thus inappropriate expression of both bcl-2 and Fas can result in SLE
      like autoimmune disease in mice. Research is now in progress to ascertain whether
      quantitative or functional abnormalities in these molecules exist in human SLE
      patients and contribute to the pathogenesis of the disease in some or all cases.

PMID- 7524705
TI  - A study of mast cells in autoimmune mice: the proliferative response of
      autoimmune mast cells to cytokines.
AB  - To investigate the mechanisms underlying the increased number of mast cells in
      autoimmune mice, the proliferative response of autoimmune mast cells to cytokines
      was examined. Bone marrow cells from autoimmune NZB mice produced scarcely any
      bone marrow derived mast cells (BMMCs) in the presence of interleukin 3 (IL-3),
      but were able to generate BMMCs when cultured with pokeweed mitogen-stimulated
      spleen cell conditioned medium (PWM-SCM). In contrast, NZB BMMCs showed very
      little proliferation in the presence of PWM-SCM, but proliferated strongly when
      cultured with stem cell factor (SCF). Non-autoimmune NZW BMMCs showed a strong
      proliferative response to both IL-3 and PWM-SCM, but proliferated weakly in
      culture with SCF. Autoimmune NZB x NZW F1 (B/W) BMMCs shared the proliferative
      activities of both NZB and NZW BMMCs, showing strong proliferation in response to
      IL-3, PWM-SCM and SCF. All strains (including other non-autoimmune strains)
      except for NZW demonstrated synergism between PWM-SCM and SCF. This study
      suggests that the strong proliferative response of autoimmune mast cells to SCF
      plays a major role in, and that other cytokines are partially responsible for,
      increasing the number of mast cells in autoimmune mice. These mechanisms are
      discussed in relation to both constitutive and inducible hematopoiesis.

PMID- 7524706
TI  - Identification of epitopes and affinity purification of thyroid stimulating auto
      antibodies using synthetic human TSH receptor peptides.
AB  - We prepared a series of overlapping peptides (29 in total, 20 amino acids each)
      containing the sequence of the entire extracellular domain of the human TSH
      receptor. Three peptides (181-200, 376-394, and EC3 (629-639)) bound IgG from
      patients with Graves' disease in an enzyme linked immunoassay. Peptide 181-200
      bound IgG from 9 of 10, EC3 from 8 of 10, and 376-394 from 6 of 10 patients
      respectively, compared to 0 of 9 controls. We affinity purified TSHr auto
      antibodies from four Graves' patients using the three above noted peptides bound
      to epoxy-activated sepharose. Thyroid stimulating activity was enriched in the
      bound fraction from at least two of the three peptide affinity columns in each of
      the four patients, although the pattern of affinity enrichment differed between
      patients. One patient was found to possess a combination of stimulatory and
      inhibitory TSHr antibodies and, after affinity purification, the anti-376-394 and
      anti-EC3 fractions were enriched in stimulatory activity, suggesting that those
      regions of the receptor were epitopes for stimulatory antibodies. However,
      affinity purification against peptide 181-200 produced an IgG preparation that
      was not stimulatory, but was a potent thyroid inhibitor. Thus, we have not only
      partially purified TSHr auto-antibodies, but also successfully separated
      stimulatory and inhibitory antibodies from a single patient using combination
      TSHr peptide affinity.

PMID- 7524707
TI  - Gap junction channels: yes, there are substates, but what does that mean?

PMID- 7524708
TI  - Modeling state-dependent inactivation of membrane currents.
AB  - Inactivation of many ion channels occurs through largely voltage-independent
      transitions to an inactivated state from the open state or from other states in
      the pathway leading to opening of the channel. Because this form of inactivation
      is state-dependent rather than voltage-dependent, it cannot be described by the
      standard Hodgkin-Huxley formalism used in virtually all modeling studies of
      neuronal behavior. Using two examples, cumulative inactivation of the Kv3
      potassium channel and inactivation of the fast sodium channel, we extend the
      standard formalism for modeling macroscopic membrane currents to account for
      state-dependent inactivation. Our results provide an accurate description of
      cumulative inactivation of the Kv3 channel, new insight into inactivation of the
      sodium channel, and a general framework for modeling macroscopic currents when
      state-dependent processes are involved. In a model neuron, the macroscopic Kv3
      current produces a novel short-term memory effect and firing delays similar to
      those seen in hippocampal neurons.

PMID- 7524709
TI  - Analysis of a novel double-barreled anion channel from rat liver rough
      endoplasmic reticulum.
AB  - The presence of anionic channels in stripped rough endoplasmic reticulum
      membranes isolated from rat hepatocytes was investigated by fusing microsomes
      from these membranes to a planar lipid bilayer. Several types of anion-selective
      channels were observed including a voltage-gated Cl- channel, the activity of
      which appeared in bursts characterized by transitions among three distinct
      conductance levels of 0 pS (0 level), 160 pS (O1 level), and 320 pS (O2 level),
      respectively, in 450 mM (cis) 50 mM (trans) KCl conditions. A chi 2 analysis on
      current records where interburst silent periods were omitted showed that the
      relative probability of current levels 0 (baseline), O1, and O2 followed a
      binomial statistic. However, measurements of the conditional probabilities
      W(level 0 at tau/level O2 at 0) and W(level O2 at tau/level 0 at 0) provided
      clear evidence of direct transitions between the current levels 0 and O2 without
      any detectable transitions to the intermediate level O1. It was concluded on the
      basis of these results that the observed channel was controlled by at least two
      distinct gating processes, namely 1) a voltage-dependent activation mechanism in
      which the entire system behaves as two independent monomeric channels of 160 pS
      with each channel characterized by a simple Open-Closed kinetic, and 2) a slow
      voltage-dependent process that accounts for both the appearance of silent periods
      between bursts of channel activity and the transitions between the current levels
      0 and O2. Finally, an analysis of the relative probability for the system to be
      in levels 0, O1, and O2 showed that our results are more compatible with a model
      in which all the states resulting from the superposition of the two independent
      monomeric channels have access at different rates to a common inactivated state
      than with a model where a simple Open-Closed main gate either occludes or exposes
      simultaneously two independent 160-pS monomers.

PMID- 7524710
TI  - Voltage-dependent gating of single gap junction channels in an insect cell line.
AB  - De novo formation of cell pairs was used to examine the gating properties of
      single gap junction channels. Two separate cells of an insect cell line (clone
      C6/36, derived from the mosquito Aedes albopictus) were pushed against each other
      to provoke formation of gap junction channels. A dual voltage-clamp method was
      used to control the voltage gradient between the cells (Vj) and measure the
      intercellular current (Ij). The first sign of channel activity was apparent 4.7
      min after cell contact. Steady-state coupling reached after 30 min revealed a
      conductance of 8.7 nS. Channel formation involved no leak between the intra- and
      extracellular space. The first opening of a newly formed channel was slow (25-28
      ms). Each preparation passed through a phase with only one operational gap
      junction channel. This period was exploited to examine the single channel
      properties. We found that single channels exhibit several conductance states with
      different conductances gamma j; a fully open state (gamma j(main state)), several
      substates (gamma j(substates)), a residual state (gamma j(residual)) and a closed
      state (gamma j(closed)). The gamma j(main state) was 375 pS, and gamma
      j(residual) ranged from 30 to 90 pS. The transitions between adjacent substates
      were 1/7-1/4 of gamma j(main state). Vj had no effect on gamma j(main state), but
      slightly affected gamma j (residual). The lj transitions involving gamma
      j(closed) were slow (15-60 ms), whereas those not involving gamma j(closed) were
      fast (< 2 ms). An increase in Vj led to a decrease in open channel probability.
      Depolarization of the membrane potential (Vm) increased the incidence of slow
      transitions leading to gamma j(closed). We conclude that insect gap junctions
      possess two gates, a fast gate controlled by Vj and giving rise to gamma
      j(substates) and gamma j(residual), and a slow gate sensitive to Vm and able to
      close the channel completely.

PMID- 7524712
TI  - A geometric sequence that accurately describes allowed multiple conductance
      levels of ion channels: the "three-halves (3/2) rule".
AB  - Ion channels can express multiple conductance levels that are not integer
      multiples of some unitary conductance, and that interconvert among one another.
      We report here that for 26 different types of multiple conductance channels, all
      allowed conductance levels can be calculated accurately using the geometric
      sequence gn = g(o) (3/2)n, where gn is a conductance level and n is an integer >
      or = 0. We refer to this relationship as the "3/2 Rule," because the value of any
      term in the sequence of conductances (gn) can be calculated as 3/2 times the
      value of the preceding term (gn-1). The experimentally determined average value
      for "3/2" is 1.491 +/- 0.095 (sample size = 37, average +/- SD). We also verify
      the choice of a 3/2 ratio on the basis of error analysis over the range of ratio
      values between 1.1 and 2.0. In an independent analysis using Marquardt's
      algorithm, we further verified the 3/2 ratio and the assignment of specific
      conductances to specific terms in the geometric sequence. Thus, irrespective of
      the open time probability, the allowed conductance levels of these channels can
      be described accurately to within approximately 6%. We anticipate that the "3/2
      Rule" will simplify description of multiple conductance channels in a wide
      variety of biological systems and provide an organizing principle for channel
      heterogeneity and differential effects of channel blockers.

PMID- 7524711
TI  - Superposition properties of interacting ion channels.
AB  - Quantitative analysis of patch clamp data is widely based on stochastic models of
      single-channel kinetics. Membrane patches often contain more than one active
      channel of a given type, and it is usually assumed that these behave
      independently in order to interpret the record and infer individual channel
      properties. However, recent studies suggest there are significant channel
      interactions in some systems. We examine a model of dependence in a system of two
      identical channels, each modeled by a continuous-time Markov chain in which
      specified transition rates are dependent on the conductance state of the other
      channel, changing instantaneously when the other channel opens or closes. Each
      channel then has, e.g., a closed time density that is conditional on the other
      channel being open or closed, these being identical under independence. We relate
      the two densities by a convolution function that embodies information about, and
      serves to quantify, dependence in the closed class. Distributions of observable
      (superposition) sojourn times are given in terms of these conditional densities.
      The behavior of two channel systems based on two- and three-state Markov models
      is examined by simulation. Optimized fitting of simulated data using reasonable
      parameters values and sample size indicates that both positive and negative
      cooperativity can be distinguished from independence.

PMID- 7524713
TI  - Axolemmal and septal conduction in the impedance of the earthworm medial giant
      nerve fiber.
AB  - Ionic conduction in the axolemmal and septal membranes of the medial giant fiber
      (MGF) of the earthworm (EW) Lumbricus terrestris was assessed by impedance
      spectroscopy in the frequency range 2.5-1000 Hz. Impedance loci in the complex
      plane were described by two semi-circular arcs, one at a lower characteristic
      frequency (100 Hz) and the other at a higher frequency (500 Hz). The lower
      frequency arc had a chord resistance of 53 k omega and was not affected by
      membrane potential changes or ion channel blockers [tetrodotoxin (TTX), 3,4
      diaminopyridine (3,4-DAP), 4-aminopyridine (4-AP), and tetraethylammonium (TEA)].
      The higher frequency arc had a chord resistance of 274 k omega at resting
      potential, was voltage-dependent, and was affected by the addition of TTX, 3,4
      DAP, 4-AP, and TEA to the physiological EW salines. When all four blockers were
      added to the bathing solution, the impedance locus was described by two voltage
      independent arcs. Considering the effects of these and other (i.e., Cd and Ni)
      ion channel blockers, we conclude that: 1) the higher frequency locus reflects
      conduction by voltage-sensitive ion channels in the axolemmal membrane, which
      contains at least four ion channels selective for sodium, calcium, and potassium
      (delayed rectifier and calcium-dependent), and 2) the lower frequency locus
      reflects voltage-insensitive channels in the septal membrane, which separates
      adjacent MGFs.

PMID- 7524714
TI  - Temperature dependence of conductivity in electrolyte solutions and ionic
      channels of biological membranes.
AB  - Temperature is a key parameter in the description of any physical system.
      Experimental study of the temperature dependence of conductivity is very valuable
      in building and testing theoretical models. This fact does not appear to be fully
      appreciated and exploited in the study of ionic channels of biological membranes
      owing in part to the lack of an adequate theory for the temperature dependence of
      conductivity in electrolyte solutions. To redress this imbalance, and to
      encourage further temperature-dependence studies in ionic channels, we first give
      explicit expressions for the conductivity of ions in electrolyte solutions in
      terms of the microscopic parameters of the liquid. We then propose that the
      dynamics of ion transport in membrane channels are similar to that in bulk
      electrolyte solutions, except that ions permeating the pore need to surmount a
      potential barrier, the height of which can be deduced experimentally. Finally, we
      use our model to analyze the conductance-temperature relationships obtained in
      two types of single ionic channels.

PMID- 7524715
TI  - Epitope analysis of human IL-6 receptor gp80 molecule with monoclonal antibodies.
AB  - Gp80 human IL-6R was studied using 7 murine mAb (M37, M91, M113, M139, M164, M182
      and M195) obtained after fusion of splenocytes of Balb/c mice immunised with a
      mixture of recombinant IL-6 receptor (rIL-6R) and cells from 2 cell lines
      expressing IL-6R. These were U266, which is IL-6 independent and XG-1 which is IL
      6-dependent. In ELISA the 7 mAb reacted against the rIL-6R and against the
      natural soluble form found in plasma (nIL-6R), which both lack transmembrane and
      cytoplasmic domains. However, M195 reacted less with the natural than with the
      recombinant soluble IL-6R. Using FACS analysis, the 7 mAb were shown to bind to
      U266 cells but not to the Namalva cell line which is deprived of IL-6R. This
      showed that they all recognised the membrane form of the IL-6R. Three of the anti
      IL-6R mAb reacted with rIL-6R by Western blotting. Four different epitopes of the
      molecule were identified, either by cross-blocking experiments of mAb binding to
      IL6R in ELISA or by the biosensor Biacore technology. A group of 4 mAb (M37,
      M113, M139 and M164) and another mAb (M195) identified 2 different epitopes
      involved in IL-6 binding. These antibodies were able to inhibit the binding of IL
      6 to IL-6R and the proliferation of the IL-6-dependent XG-1 cell line. M91 and
      M182 recognized 2 other epitopes that were not involved in IL-6 binding. As
      expected, M91 did not inhibit XG-1 proliferation; in contrast, M182 interfered
      with the proliferative response of the XG-1 cell line.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7524716
TI  - IL-6, IL-8 and TNF production by cytokine and lipopolysaccharide-stimulated human
      renal cortical epithelial cells in vitro.
AB  - The capacity of renal epithelial cells to produce IL-6, IL-8 and TNF was
      investigated. Cultures of explanted human renal cortical epithelial cells (RCEC)
      were established, and cytokine-release and mRNA expression by these cells were
      measured. IL-6, IL-8 and TNF release were measured after stimulation with IL-1
      beta TNF-alpha, LPS and the phorbol esther PMA. All these agents were found to
      induce increased release of the three cytokines. Whilst no spontaneous TNF
      release occurred, IL-6 and IL-8 were continuously released by non-stimulated RCEC
      cultures. IL-1 beta was the most potent trigger, enhancing both RCEC cytokine
      release and expression of IL-6, IL-8 and TNF mRNA. Indomethacin, budesonide,
      cyclosporin and FK 506 were tested for their influence on RCEC cytokine release.
      Only the steroid budesonide appeared to reduce both spontaneous and IL-1 beta
      induced cytokine release. Our data demonstrate stimulus specific release of IL-6,
      IL-8 and TNF by RCEC, and suggest that cytokine cell-to-cell communication may be
      important in regulating inflammatory processes in the kidney.

PMID- 7524717
TI  - Interleukin-1 stimulates the expression of type I and type II interleukin-1
      receptors in the rat insulinoma cell line Rinm5F; sequencing a rat type II
      interleukin-1 receptor cDNA.
AB  - The insulin secreting rat Rinm5F cells are often used to study the cytotoxic
      actions of interleukin-1 (IL-1) on pancreatic beta-cells. We demonstrate here
      that Rinm5F insulinoma cells express both type I and type II interleukin-1
      receptor (IL-1R) mRNAs and gene products. IL-1R agonists, recombinant murine IL-1
      alpha (rmIL-1 alpha, 10 ng/ml) and recombinant rat IL-1 beta (rrIL-1 beta, 100
      pg/ml or 10 ng/ml) induce the upregulation of mRNA expression for both types of
      IL-1 receptors (IL-1Rs). This effect of rrIL-1 beta is antagonised by
      preincubation with recombinant human interleukin 1 receptor antagonist protein
      (rhIL-1ra, 5 micrograms/ml). Furthermore, this rrIL-1 beta induced upregulation
      of IL-1R mRNAs is blocked by actinomycin D (7.5 micrograms/ml), whereas
      cycloheximide (20 micrograms/ml) has no effect. The phorbol ester PMA (20 nM)
      upregulates the expression of mRNAs both IL-1 receptors, whereas glucose (50 mM)
      upregulates the expression of the type I IL-1R mRNA only. Pretreatment of cells
      with pertussis toxin (100 ng/ml) partially blocks the rrIL-1 beta induced
      expression of mRNA for the type I and, to a lesser extent, the type II IL-1R.
      Incubation of the cells with rrIL-1 beta also induces a time-dependent expression
      of c-fos, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha)
      mRNAs. Binding studies with 125I-recombinant human IL-1 beta (125I-rhIL-1 beta)
      indicate that IL-1R gene products, with the ligand binding characteristics of the
      type I IL-1R, are constitutively present on Rinm5F cells. Treatment with rrIL-1
      beta (6h) increases the number of 125I-rhIL-1 beta binding sites on Rinm5F cells.
      We have also demonstrated that the number of type II IL-1R binding sites
      increases after induction with rrIL-1 beta (6h), by indirect immunofluorescence
      using a monoclonal antibody (ALVA 42) raised against the human type II IL-1R.
      Furthermore, we have sequenced the type II IL-1R cDNA in the rat insulinoma
      Rinm5F cells. The comparison of the amino acid sequence of the rat type II IL-1R
      with that of the mouse and human type II IL-1Rs shows 90% and 62% amino acid
      identity, respectively. The most important difference between the human and
      murine type II IL-1Rs, and this rat type II IL-1R cDNA, is an open reading frame
      coding for a six amino acid longer, strongly charged (QIKEMK), cytosolic
      domain.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7524719
TI  - Pro: tranexamic acid is better than aprotinin in decreasing bleeding after
      cardiac surgery.

PMID- 7524718
TI  - Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal
      disease.
AB  - Impaired platelet function and a bleeding tendency are well-recognized
      complications of chronic renal failure. Because the fibrinogen receptor GPIIb
      IIIa plays a central role in platelet aggregation and adhesion to the
      subendothelium, it was reasoned that a defect in this receptor may underlie the
      impaired platelet function in uremia. To test this hypothesis, the function of
      this receptor in the platelets of 11 uremic patients was studied. Aggregation
      studies were performed with flow cytometric techniques with anti-GPIIb-IIIa
      conformation-specific monoclonal antibodies (mAb) (anti-LIBS1 and anti-PMI-1).
      Antifibrinogen and antithrombospondin mAb were used to characterize fibrinogen
      binding to GPIIb-IIIa and the release of alpha-granules, respectively. Platelets
      from patients with chronic renal failure showed significantly decreased binding
      of conformation-dependent anti-LIBS1 mAb after ADP, phorbol myristate acetate, or
      RGD-peptide stimulation compared with normal controls, suggesting a defect
      related to the ability of the fibrinogen receptor to undergo a conformational
      change. Moreover, antifibrinogen and antithrombospondin binding to activated
      platelets were reduced in uremic patients, implying impairment of both ligand
      binding and alpha-granule release. Hemodialysis partially restored GPIIb-IIIa
      function, which may account for the observed effects of this therapy in restoring
      platelet aggregation. These findings indicate that platelets of patients with
      chronic renal failure reveal an aggregation defect at least partially due to an
      intrinsic GPIIb-IIIa dysfunction and the presence of a putative uremic toxin that
      inhibits fibrinogen binding to GPIIb-IIIa.

PMID- 7524720
TI  - Con: tranexamic acid is not better than aprotinin in decreasing bleeding after
      cardiac surgery.

PMID- 7524722
TI  - Prevalence of hepatitis C virus markers in Sri Lankan patients with alcoholic
      cirrhosis.
AB  - A high prevalence of antibodies against hepatitis C virus (HCV) has been reported
      in patients with alcoholic cirrhosis. There are, however, doubts regarding the
      specificity of the first generation anti-HCV antibody assays used. We
      prospectively investigated HCV status in 47 Sri Lankan patients with alcoholic
      cirrhosis. A first generation assay (Ortho HCV enzyme-linked immunosorbent assay
      [ELISA]) and two second generation tests (Abbott HCV enzyme immunoassay and
      United Biomedical Incorporated HCV enzyme immunoassay) were used. Positive
      results were confirmed by the second generation recombinant immunoblot assay
      (RIBA 2). Of the 47 patients (46 males, mean age 41.7 years), 17 (36.2%) had
      previously had one or more blood or plasma transfusions. Seven (14.9%) of the
      samples were positive for anti-HCV antibodies using the Ortho-HCV ELISA, but only
      one (2.1%) sample was positive when tested with the second generation assays. The
      positive result was confirmed by RIBA 2. The prevalence of HCV in the patients
      was low despite many of them being exposed to blood or blood products. Hepatitis
      C virus, therefore, may not be an important pathogenic factor in alcoholic
      cirrhosis in Sri Lanka.

PMID- 7524721
TI  - Mass screening for hepatocellular carcinoma: experience in Hokkaido, Japan.
AB  - Mass screening for liver cancer based mainly on abdominal ultrasound was begun in
      major cities of Hokkaido, Japan, in November 1981, to enable early detection and
      treatment of hepatocellular carcinoma (HCC). Serum alpha-fetoprotein levels were
      also measured to minimize false negative studies. Examinees included those who
      sought liver disease screening as well as high risk individuals: hepatitis B
      surface antigen carriers and those with a past or current liver disease, history
      of blood transfusion, family history of liver cancer, and more recently those
      with positive anti-hepatitis C antibodies. The examination was carried out on
      each Saturday and Sunday as one round, and by February 1992 48 rounds had been
      performed. A total of 8090 individuals were investigated, and HCC was detected in
      91 with a detection rate of 1.12%. This rate was 1.6% among 5684 individuals who
      were selected for high risk. Cumulative rates of survival among these patients
      were 79.0% at 1 year, 43.8% at 3 years, 19.3% at 5 years and 15.4% at 7 years.
      These survival rates were comparable with those for the patients with HCC
      diagnosed during follow-up of chronic liver disease and treated at our hospital.
      The cost for detecting one HCC patient in this programme was 2,660,000 yen
      (approximately US$25,000), which was less than those for some other types of
      cancer in a similar setting. Considering the high detection rate in this
      programme, we feel that similar programmes should be encouraged and supported.

PMID- 7524723
TI  - Hepatitis C and B virus infections in populations at low or high risk in Ho Chi
      Minh and Hanoi, Vietnam.
AB  - Inhabitants and patients of two cities in Vietnam were tested for antibodies to
      hepatitis C virus (anti-HCV), hepatitis B surface antigen (HBsAg) and antibody to
      HBsAg (anti-HBs). Anti-HCV was detected in 43 (9%) of 491 individuals without
      liver disease in Ho Chi Minh, more frequently (P < 0.001) than in 18 (4%) of 511
      in Hanoi. There was no apparent age-specific distribution of anti-HCV. Among
      inhabitants of both cities, HBsAg and anti-HBs were frequent, detected in 10-14%
      and 35-37%, respectively; the prevalence of anti-HBs increased in parallel with
      age. Among individuals at high risk, the prevalence of anti-HCV was particularly
      high in drug users (58/67 or 87%) and patients on maintenance haemodialysis
      (15/28 or 54%) or with haemophilia (7/24 or 29%) in Ho Chi Minh, and in drug
      users in Hanoi (61/200 or 31%). Prevalence of HBsAg and anti-HBs in high-risk
      groups was not different from those in the general population. Screening of anti
      HCV in blood donors in Vietnam is of urgent necessity because blood supply is
      dependent on commercial blood donors, many of whom are drug users at high risk.

PMID- 7524724
TI  - Expression of constitutive nitric oxide synthase in a primary neuronal culture.
AB  - Nitric oxide (NO), a short-lived, highly diffusible free radical, is a messenger
      molecule produced through the conversion of arginine to citrulline by NO synthase
      (NOS). In the CNS, NO functions as an important neuromodulator. We now report
      that cerebellar granule cells in culture express the constitutive form of NOS
      (cNOS). The expression is demonstrated both at the level of RNA, by RNA-specific
      reverse transcription-polymerase chain reaction (RT-PCR), and of protein, by
      immunostaining and by enzymatic activity. Cerebellar granule cells can thus serve
      as a tool to study the regulation of expression and activity of cNOS in a defined
      environment.

PMID- 7524726
TI  - Targeted deletion of psaJ from the cyanobacterium Synechocystis sp. PCC 6803
      indicates structural interactions between the PsaJ and PsaF subunits of
      photosystem I.
AB  - Photosystem I catalyzes the light-driven oxidation of plastocyanin or cytochrome
      c6 and the reduction of ferredoxin or flavodoxin. PsaJ is a 4.4 kDa hydrophobic
      subunit of photosystem I from cyanobacteria and chloroplasts. To investigate the
      function of PsaJ, we generated a mutant strain of the cyanobacterium
      Synechocystis sp. PCC 6803 in which the psaJ gene is replaced by a gene for
      chloramphenicol resistance. Deletion of psaJ led to a reduction in the steady
      state RNA level from psaF which is located upstream from psaJ.
      Immunoquantification using an anti-PsaF antibody revealed a significant decrease
      in the amount of PsaF in membranes of the mutant strain. Trimeric photosystem I
      complexes isolated from the mutant strain using n-dodecyl beta-D-maltoside lacked
      PsaJ, contained ca. 80% less PsaF, but maintained wild-type levels of other
      photosystem I subunits. In contrast, the photosystem I purified using Triton X
      100 contained less than 2% PsaF when compared to the wild type, showing the more
      extractable nature of PsaF in PsaJ-less photosystem I in the presence of Triton X
      100. PsaE was more accessible to removal by NaI in a mutant strain lacking PsaF
      and PsaJ than in the wild type. The presence of PsaF in photosystem I from the
      PsaJ-less strain did not alter the increased susceptibility of PsaE to removal by
      NaI. These results indicate an interaction between PsaJ and PsaF in the
      organization of the complex.

PMID- 7524725
TI  - Cloning of omega 3 desaturase from cyanobacteria and its use in altering the
      degree of membrane-lipid unsaturation.
AB  - Cyanobacteria respond to a decrease in temperature by desaturating fatty acids of
      membrane lipids to compensate for the decrease in membrane fluidity. Among
      various desaturation reactions in cyanobacteria, the desaturation of the omega 3
      position of fatty acids is the most sensitive to the change in temperature. In
      the present study, we isolated a gene, designated desB, for the omega 3
      desaturase from the cyanobacterium, Synechocystis sp. PCC 6803. The desB gene
      encodes a protein a 359 amino-acid residues with molecular mass of 41.9 kDa. The
      desB gene is transcribed as a monocistronic operon that produced a single
      transcript of 1.4 kb. The level of the desB transcript in cells grown at 22
      degrees C was 10 times higher than that in cells grown at 34 degrees C. In order
      to manipulate the fatty-acid unsaturation of membrane lipids, the desB gene in
      Synechocystis sp. PCC 6803 was mutated by insertion of a kanamycin-resistance
      gene cartridge. The resultant mutant was unable to desaturate fatty acids at the
      omega 3 position. The desA gene, which encodes the delta 12 desaturase of
      Synechocystis sp. PCC 6803, and the desB gene were introduced into Synechococcus
      sp. PCC 7942. Whilst the parent cyanobacterium can only desaturate membrane
      lipids at the delta 9 position of fatty acids, the resultant transformant was
      able to desaturate fatty acids of membrane lipids at the delta 9, delta 12 and
      omega 3 positions. These results confirm the function of the desB gene and
      demonstrate that it is possible to genetically manipulate the fatty-acid
      unsaturation of membrane lipids in cyanobacteria.

PMID- 7524727
TI  - Cloning of the cpcE and cpcF genes from Synechococcus sp. PCC 6301 and their
      inactivation in Synechococcus sp. PCC 7942.
AB  - Two open reading frames denoted as cpcE and cpcF were cloned and sequenced from
      Synechococcus sp. PCC 6301. The cpcE and cpcF genes are located downstream of the
      cpcB2A2 gene cluster in the phycobilisome rod operon and can be transcribed
      independently of the upstream cpcB2A2 gene cluster. The cpcE and cpcF genes were
      separately inactivated by insertion of a kanamycin resistance cassette in
      Synechococcus sp. PCC 7942 to generate mutants R2EKM and R2FKM, respectively,
      both of which display a substantial reduction in spectroscopically detectable
      phycocyanin. The levels of beta- and alpha-phycocyanin polypeptides were reduced
      in the R2EKM and R2FKM mutants although the phycocyanin and linker genes are
      transcribed at normal levels in the mutants as in the wild type indicating the
      requirement of the functional cpcE and cpcF genes for normal accumulation of
      phycocyanin. Two biliprotein fractions were isolated on sucrose density gradient
      from the R2EKM/R2FKM mutants. The faster sedimenting fraction consisted of intact
      phycobilisomes. The slower sedimenting biliprotein fraction was found to lack
      phycocyanin polypeptides, thus no free phycocyanin was detected in the mutants.
      Characterization of the phycocyanin from the mutants revealed that it was
      chromophorylated, had a lambda max similar to that from the wild type and could
      be assembled into the phycobilisome rods. Thus, although phycocyanin levels are
      reduced in the R2EKM and R2FKM mutants, the remaining phycocyanin seems to be
      chromophorylated and similar to that in the wild type with respect to
      phycobilisome rod assembly and energy transfer to the core.

PMID- 7524728
TI  - Gene family encoding basic pathogenesis-related 1 proteins in barley.
AB  - A genomic (prb1) and two cDNA clones (PRb1-2 and PRb1-3) corresponding to two new
      barley basic PR-1 proteins (prb1-2 and prb1-3) were isolated from Hordeum
      vulgare. Genomic analysis of DNA suggests that the barley genome contains at
      least 6 members corresponding to the gene family encoding PR-1 proteins.
      Expression of these genes was induced in primary leaf tissues of the H. vulgare
      cv. Psaknon 4* (F14) Man. carrying Mlp resistance gene (cv. Mlp) and the near
      isogenic susceptible cultivar (cv. mlp) after inoculation with Erysiphe graminis
      f. sp. hordei.

PMID- 7524729
TI  - B-cell prolymphocytic leukemia expressing CD13 antigen.
AB  - Although the expression of myeloid-associated antigen CD13 has been reported in
      aggressive B-cell chronic lymphocytic leukemia, its expression in other mature B
      cell neoplasms appears to be rare. We report a 74-year-old female with B-cell
      prolymphocytic leukemia (B-PLL) expressing CD13 antigen. On admission,
      splenomegaly was noted. Hematological examination revealed a platelet count of 90
      x 10(9)/l and a white cell count of 68 x 10(9)/l with 73% PLL cells. The
      hemoglobin concentration was 10.6 g/dl. A bone marrow aspirate showed a
      normocellular marrow with 64% PLL cells. Surface marker analysis of the PLL cells
      was positive for CD11b, CD13, CD19, CD20, CD24, HLA-DR, FMC7, mu and lambda.
      Simultaneous expression of CD13 and CD19 antigen was confirmed by dual color flow
      cytometry. Southern blot analysis of DNA from circulating mononuclear cells gave
      a rearranged band for the immunoglobulin gene (JH) but not for TCR-beta.
      Cytogenetic analysis of marrow cells showed an abnormal karyotype involving
      numbers 1, 7, 10, 12, 14, 15 chromosomes.

PMID- 7524731
TI  - Urinary beta 2- and alpha 1-microglobulin levels in normal subjects in Singapore.
AB  - Differing normal values for urinary beta 2-microglobulin have been reported for
      different countries. In this study, we have attempted to establish the urinary
      beta 2- and alpha 1-microglobulin levels of apparently healthy subjects in
      Singapore. Urine samples collected from 271 subjects were analysed. The subjects
      ranged from 19 to 62 years old, with a mean age of 36.8 years. The majority
      (84.5%) were non-smokers. Urine samples with a pH level < 5.5 were excluded from
      the analysis. The urinary beta 2- and alpha 1-microglobulin values followed log
      normal distributions. Their 95th percentiles were 288 micrograms/g creatinine and
      7.35 mg/g creatinine, respectively. Statistically significant differences were
      found between sexes and ethnic groups for urinary beta 2-microglobulin values.
      Both alpha 1- and beta 2-microglobulin values increased significantly with age.
      Smokers had significantly higher urinary alpha 1-microglobulin values.

PMID- 7524730
TI  - [The palliative closure of an esophageal-bronchial fistula with a coated metal
      stent].

PMID- 7524732
TI  - Staining for acid-fast bacilli: hot or cold?

PMID- 7524735
TI  - Detection of an L-selectin ligand on a hematopoietic progenitor cell line.
AB  - L-selectin, the peripheral lymph node "homing receptor," is an adhesion protein
      that mediates lymphocyte binding to lymph node high endothelial venules. Ligands
      for this protein have been identified only on endothelial cells, and recent
      murine studies indicate that CD34 on endothelial cells is an L-selectin ligand.
      To investigate whether CD34 expressed on hematopoietic cells functions as an L
      selectin ligand, we used an in vitro binding assay to examine lymphocyte
      adherence to KG1a, a CD34+ human hematopoietic progenitor cell line. We observed
      specific L-selectin-mediated adherence of lymphocytes to KG1a: the binding was
      calcium-dependent, was strictly inhibited by anti-L-selectin antibodies and by
      carbohydrate ligands of L-selectin, and was abrogated by induction of L-selectin
      shedding from the lymphocyte membrane by treatment with phorbol esters. However,
      blocking studies using anti-CD34 antibodies, and experiments using KG1a cells
      sorted for CD34 expression and COS-7 cells transfected with full-length CD34 cDNA
      indicate that the ligand on KG1a is not CD34; moreover, RPMI 8402, a CD34+ cell
      line, does not support lymphocyte adherence in the binding assay. Treatment of
      KG1a with the enzymes neuraminidase, chymotrypsin, and bromelain abrogated
      lymphocyte binding to the cells, indicating that the ligand is a glycoprotein.
      These experiments show that CD34 on hematopoietic cells is not an L-selectin
      ligand and provide the first evidence of a ligand for L-selectin present on a non
      endothelial cell.

PMID- 7524733
TI  - Pivotal role of the B7:CD28 pathway in transplantation tolerance and tumor
      immunity.
AB  - The above story illustrates the translation of basic scientific discoveries to
      the clinic. In vitro and preclinical in vivo experimentation suggests that
      modulation of the B7:CD28 pathway will result in either amplification or
      suppression of the immune response. Considering the frequency with which diseases
      characterized by either inadequate or dysregulated immune function present to the
      practicing hematologist or oncologist, it is not difficult to envisage clinical
      applications for reagents that modulate this pathway. However, we still have much
      to learn about the function and clinical potential of this and other potentially
      redundant costimulatory pathways and therefore we suspect that this story will
      become considerably more complex over the next few years.

PMID- 7524734
TI  - The hematopoietic stem cell antigen, CD34, is not expressed on the malignant
      cells in multiple myeloma.
AB  - Autologous stem cell transplantation has become an important therapy in multiple
      myeloma (MM). To develop adequate autograft purging methods, it is necessary to
      determine whether antigens expressed on early hematopoietic progenitors exist on
      malignant cells. The Ig heavy chain produced by the MM cells shows evidence of
      prior somatic mutation without intraclonal diversity. As a result, this sequence
      can be used as a specific marker to detect all members of the malignant clone.
      The Ig heavy chain sequence expressed by the MM cells was obtained in five
      patients with advanced disease. Patient specific oligonucleotide primers were
      designed based on the complementarity determining regions (CDR) of each MM Ig
      sequence and used to amplify DNA by polymerase chain reaction for the detection
      of malignant cells. A highly purified collection of CD34+ cells was obtained
      after passage of the initial bone marrow cells through an immunoadsorption column
      and fluorescence-activated cell sorting. Despite an assay sensitivity of 1 tumor
      cell in 2,500 to 44,000 normal cells, none of the CD34+ samples showed product
      with the myeloma-specific CDR primers. Therefore, positive selection for cells
      bearing this antigen should yield a tumor-free autograft capable of providing
      hematopoietic recovery after myeloablative chemotherapy.

PMID- 7524736
TI  - Natural interferon-alpha versus its combination with 6-methyl-prednisolone in the
      therapy of type II mixed cryoglobulinemia: a long-term, randomized, controlled
      study.
AB  - Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis
      characterized by circulating cold-precipitable proteins that usually consists of
      polyclonal IgG and monoclonal IgM kappa with rheumatoid factor (RF) activity. Its
      etiology is unknown, although recent evidence strongly suggests that hepatitis C
      virus (HCV) plays a major role. Plasmapheresis, corticosteroids, and cytotoxic
      drugs have been used in the therapy of MC patients. Recently, favorable results
      with recombinant interferon-alpha (rIFN alpha) have been reported. To further
      assess its effectiveness, we studied the effects of natural human interferon
      alpha (nIFN alpha), alone and in combination with 6-methyl-prednisolone (PDN), in
      a prospective, randomized, controlled trial in patients with symptomatic MC.
      Sixty-five patients were enrolled onto the trial, 52 (80%) of whom presented
      serum anti-HCV antibodies and specific genomic RNA sequences. Fifteen patients
      received nIFN alpha (3 MU) intramuscularly (IM) three times weekly, whereas 17
      patients also received 16 mg/d of PDN orally on non-IFN days. Moreover, 18
      patients received 16 mg/d of PDN only, and 15 were untreated. Treatment was
      discontinued after 1 year and patients were monitored for 8 to 17 months (mean,
      13). A complete response was achieved in eight of 15 patients (53.3%) treated
      with nIFN alpha and nine of 17 (52.9%) treated with nIFN alpha plus PDN, as
      compared with three of 18 patients (16.7%) who received PDN only (P < .05) and
      one of 15 (6.7%) untreated controls (P < .01). Partial response occurred in two
      of 15 (13.3%) patients treated with nIFN alpha, three of 17 (17.6%) who received
      nIFN alpha plus PDN, one of 18 (5.5%) who received PDN only, and one of 15 (6.7%)
      controls. A complete response in six patients (66.7%) was achieved within 3
      months in the group that received nIFN alpha plus PDN, as compared with two
      patients (25%) of those who received nIFN alpha alone (P < .02). In anti-HCV
      positive patients, the clinical response occurred in step with reduced or
      undetectable levels of HCV RNA and transaminase normalization. Quantification of
      circulating HCV RNA represented a good predictive response marker. The
      probability of relapse within 3 months after treatment was 100% (three of three
      patients) and 75% (six of eight patients), respectively, in patients who received
      PDN alone or nIFN alpha alone as compared with none of those who received nIFN
      alpha plus PDN (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524737
TI  - Expression of CD4 by human hematopoietic progenitors.
AB  - It has been recently reported that murine hematopoietic stem cells and
      progenitors express low levels of CD4. In this study, we have investigated by
      phenotypic and functional analysis whether the CD4 molecule was also present on
      human hematopoietic progenitors. Unfractionated marrow cells or immunomagnetic
      bead-purified CD34+ cells were analyzed by two-color fluorescence with an anti
      CD4 and an anti-CD34 monoclonal antibody (MoAb). A large fraction (25% to 50%) of
      the CD34+ cells was weakly stained by anti-CD4 antibodies. Moreover, in further
      experiments analyzing the expression of CD4 in different subpopulations of CD34+
      cells, we found that CD4 was predominantly expressed in phenotypically primitive
      cells (CD34+ CD38-/low CD71low Thy-1high, HLA-DR+/low). However, the presence of
      CD4 was not restricted to these primitive CD34+ cell subsets and was also
      detected in a smaller fraction of more mature CD34+ cells exhibiting
      differentiation markers. Among those, subsets with myelo-monocytic markers (CD13,
      CD33, CD14, and CD11b) have a higher CD4 expression than the erythroid or
      megakaryocytic subsets. In vitro functional analysis of the sorted CD34+ subsets
      in colony assays and long-term culture-initiating cell (LTC-IC) assays confirmed
      that clonogenic progenitors (colony-forming unit-granulocyte-macrophage, burst
      forming unit-erythroid, and colony-forming unit-megakaryocyte) and LTC-IC were
      present in the CD4low population. However, most clonogenic progenitors were
      recovered in the CD4- subset, whereas the CD4low fraction was greatly enriched in
      LTC-IC. In addition, CD4low LTC-IC generated larger numbers of primitive
      clonogenic progenitors than did CD4- LTC-IC. These observations suggest that, in
      the progenitor compartment, the CD4 molecule is predominantly expressed on very
      early cells. The CD4 molecule present on CD34+ cells appeared identical to the T
      cell molecule because it was recognized by three MoAbs recognizing different
      epitopes of the molecule. Furthermore, this CD4 molecule is also functional
      because the CD34+ CD4low cells are able to bind the human immunodeficiency virus
      (HIV) gp120. This observation might be relevant to the understanding of the
      mechanisms of HIV-induced cytopenias.

PMID- 7524738
TI  - Macrophage colony-stimulating factor enhances the susceptibility of macrophages
      to infection by human immunodeficiency virus and reduces the activity of
      compounds that inhibit virus binding.
AB  - The effects of macrophage colony-stimulating factor (M-CSF) on CD4 receptor
      expression, susceptibility to human immunodeficiency virus type 1 (HIV)
      infection, and anti-HIV activity of dextran sulfate and soluble-CD4 were studied
      in cultured, human primary macrophages. M-CSF stimulated macrophage cells to
      express the CD4 receptor, and this resulted in an increase of both the number of
      CD4+ cells and the density of the receptor on the cell surface. M-CSF also
      significantly enhanced the susceptibility of macrophage cells to HIV infection.
      Interestingly, the anti-HIV activity of dextran sulfate and soluble-CD4 (two
      compounds that interfere with HIV-CD4 binding with different mechanisms) was
      reduced 100-fold and fivefold, respectively, in M-CSF-treated macrophages. Human
      blood concentrations of M-CSF are reported to be similar to those used in this
      work (1,000 U/mL); thus, it is conceivable that also in vivo this cytokine may
      modify the susceptibility of macrophages to HIV and the ability of dextran
      sulfate and soluble CD4 to inhibit HIV replication. These results suggest that
      the in vitro study in M-CSF-treated macrophages of promising drugs inhibitors of
      HIV-CD4 binding could provide further insights into the potential efficacy of
      these compounds in patients.

PMID- 7524739
TI  - Growth of erythroid colonies in chronic myelogenous leukemia is independent of
      erythropoietin only in the presence of steel factor.
AB  - The mechanisms of the chronic myeloid leukemia (CML) clones proliferative
      advantage over normal clones are currently unknown. They may involve an
      insensitivity to a negative regulation of a growth factor-independent
      proliferation. Clonogenic progenitors from CML patient blood or marrow in chronic
      phase were grown either in the presence or absence of recombinant growth factors.
      No erythroid colonies were observed in the absence of any cytokine. In contrast,
      erythroid colonies composed of fully mature hemoglobinized erythroblasts (day 12
      burst-forming units-erythroid) were obtained in the presence of Steel factor (SF)
      alone. Addition of erythropoietin (Epo) to SF either had no effect on the cloning
      efficiency or increased up to 50% the number of erythroid colonies. No erythroid
      growth was observed when cultures were stimulated by interleukin-3 or granulocyte
      macrophage colony-stimulating factor alone. Similar erythroid growth in the
      presence of SF but without Epo was obtained in "serum-free" cultures when
      purified blood CML CD34+ cells were grown. This growth of erythroid colonies in
      the absence of Epo was not accounted for by an autocrine stimulation loop by Epo,
      because neutralizing antibodies against Epo did not inhibit it. This abnormal
      response to growth factor was specifically observed in the CML clone, as shown by
      the presence of the BCR-ABL transcript in all of these erythroid colonies. The
      direct implication of BCR-ABL was further documented (1) by studies of alpha
      interferon-treated patients with a chimerism in which the abnormal growth
      correlates with the presence of the malignant clone and (2) by the use of
      antisense oligonucleotide against BCR-ABL transcript, which abrogated this
      abnormal growth. Finally, erythroid growth in the SF presence was greatly
      diminished by herbimycin A, whereas, at the same concentration, this tyrosine
      kinase inhibitor had no marked effect on erythroid colony formation in the
      presence of SF plus Epo on CML or normal marrow cells. This result suggests that
      the BCR-ABL kinase activity leads directly to this Epo-independent terminal
      differentiation requiring, however, the presence of SF.

PMID- 7524741
TI  - DLA-identical bone marrow grafts after low-dose total body irradiation: the
      effect of canine recombinant hematopoietic growth factors.
AB  - Previous studies found that bone marrow (BM) allografts from DLA-identical
      littermates resulted in survival of two thirds of recipient dogs after otherwise
      lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of
      successful allografts or autologous recovery after rejection of the allografts.
      The current study asked whether survival could be further improved by treating
      allograft recipients with recombinant canine granulocyte colony-stimulating
      factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%)
      receiving allografts but no growth factors survived, 10 with successful
      allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7
      animals died, 5 from infections during BM aplasia and 2 from acute graft-versus
      host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth
      factors in addition to the BM graft survived, 17 with successful allografts
      (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died,
      all with infection related to BM aplasia after rejection of the allograft.
      Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF
      and SCF. Logistic regression analyses, which accounted for possible effects of
      TBI dose, showed a trend for improved survival in dogs receiving growth factors
      (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase
      in autologous recovery (P = .22). In agreement with previous data, we found that
      grafts of BM from DLA-identical littermates improved survival of recipient dogs
      exposed to low but otherwise lethal doses of TBI. A further improvement in
      survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF.
      Results suggest that treatment by hematopoietic growth factors along with BM
      grafts should be considered for victims of radiation accidents.

PMID- 7524740
TI  - Expression of stem cell factor and c-kit in human neuroblastoma. The Children's
      Cancer Group.
AB  - During development, mice with mutations of stem cell factor (SCF) or its receptor
      c-kit exhibit defects in melanogenesis, as well as hematopoiesis and
      gonadogenesis. Because melanocytes derive from neural crest cells, the role of
      SCF and c-kit was investigated in the neural crest-derived childhood tumor
      neuroblastoma. Using reverse transcription-polymerase chain reaction analysis,
      simultaneous expression of steady-state mRNA for the SCF ligand and its receptor
      c-kit was found in 14 of 14 (100%) human neuroblastoma cell lines and clones and
      in 8 of 18 (45%) human neuroblastoma tumor samples. Functional blockade of c-kit
      receptors in the cell lines SK-N-BE(2) and SH-SY5Y using the mouse monoclonal
      anti-c-kit antibody SR-1 resulted in a significant decrease in cellular growth
      rate when measured by either 3H-thymidine incorporation or clonogenicity. In
      addition, higher levels of c-kit mRNA expression were associated with parental
      neuroblastoma cell lines and subclones with a neuronal (N) differentiation
      phenotype, whereas lower levels of c-kit mRNA were associated with neuroblastoma
      cell line subclones having a schwannian/glial/melanocytic pattern of
      differentiation. However, the differentiation phenotype of neuroblastoma cell
      lines was not directly altered when c-kit expression was blocked using the SR-1
      antibody. In summary, these data indicate that c-kit receptor expression may play
      a significant role in the growth regulation of the two neuroblastoma cell lines
      examined and suggest that c-kit may also play a similar role in neuroblastoma
      growth regulation in vivo. Simultaneous expression of SCF and c-kit mRNA in both
      neuroblastoma cell lines and tumors implies that c-kit may act as part of an
      autocrine growth loop in conjunction with endogenous production of SCF in this
      disease.

PMID- 7524742
TI  - Optimization of conditions for ex vivo expansion of CD34+ cells from patients
      with stage IV breast cancer.
AB  - Multiple cycles of high-dose chemotherapy can be hematologically supported by
      repeated administration of peripheral blood progenitors obtained after
      mobilization using cytokine alone or in combination with chemotherapy. We have
      explored the quality of such cells and their potential to undergo ex vivo
      expansion. Twenty-five leukapheresis samples from 19 patients who had received
      extensive prior chemotherapy for stage IV breast cancer were subjected to CD34+
      cell selection using immunoaffinity columns of immunomagnetic bead separation.
      Cells were cultured in suspension in the presence of c-kit ligand, interleukin-3,
      interleukin-6, erythropoietin, and granulocyte colony-stimulating factor. Ten
      experiments were performed using weekly exchange of media and cytokines (Delta
      assay). Median myeloid and erythroid progenitors expanded 15-fold at 7 days
      (range, 7 to 43), 40-fold at 14 days (range, 18 to 470), 46-fold at 21 days
      (range, 0 to 118), and 21-fold at 28 days (range, 0 to 61). In a system using gas
      permeable bags without exchange of media or cytokine, median progenitors expanded
      13-fold at 7 days (range, 7 to 36), 14-fold at 10 days (range, 4 to 61), 14-fold
      at 12 days (range, 3 to 46), and 10-fold at 14 days (range, 1 to 35). Progenitor
      expansion less than 10-fold occurred in 8% of experiments at day 7, in 17% at day
      10, in 43% at day 12, and in 50% at day 14. When autologous plasma, autologous
      plasma processed (removal of cryoprecipitate, centrifugation, then filtration),
      or human serum were substituted for 20% fetal calf serum, the ratio of progenitor
      expansion at 7 days relative to 20% fetal calf serum for 10% human serum, 20%
      human serum, and 1% autologous plasma processed was 1.01 (range, 0.62 to 1.33),
      0.88 (range, 0.61 to 1.20), and 0.96 (range, 0.55 to 1.64), respectively. These
      findings support the feasibility of ex vivo expansion in a system free of
      nonhuman proteins of CD34(+)-derived progenitors obtained from the peripheral
      blood of patients who have received prior chemotherapy.

PMID- 7524743
TI  - Evidence for engraftment of donor-type multipotent CD34+ cells in a patient with
      selective T-lymphocyte reconstitution after bone marrow transplantation for B
      SCID.
AB  - Severe combined immunodeficiencies (SCID), a heterogeneous group of disorders of
      infancy, are fatal without treatment directed at immunologic reconstitution.
      Allogeneic bone marrow transplantation (BMT), which is such a treatment presents
      some unique features in SCID, especially when T-lymphocyte-depleted HLA
      haploidentical allografts are used. Donor-type T lymphopoiesis, less often B
      lymphopoiesis, develops, whereas myelopoiesis remains the recipient-type. Little
      is known about the engrafting cells in this peculiar lymphohematopoietic
      chimerism and the pathophysiology of the frequent failure of B-lymphocyte
      reconstitution. To address these issues, we purified CD34+ BM cells from a
      patient with selective T-lymphocyte reconstitution after HLA haploidentical BMT
      for B-SCID. Phenotypic analysis of CD34+ cells was performed by flow cytometry,
      and functional studies of donor- and recipient-type CD34+ cells were performed in
      vitro. Donor-type CD34+ cells, constituting approximately 2% of the CD34+ cells,
      were detected; both CD34+ HLA-DR- cells and CD34+ cells coexpressing B-(CD10 and
      CD19) and T-(CD2 and CD7) lymphocyte-associated cell surface molecules. Donor
      type CD34+ cells coexpressing myeloid-associated molecules (CD13, CD14, CD15, and
      CD33) were undetectable. However, donor-type CD34+ myeloid progenitors could be
      shown in functional assays. Recipient-type CD34+ cells coexpressing B- and T
      lymphocyte- as well as myeloid-associated molecules were detected, but recipient
      type CD34+ cells could not be driven into T-lymphocyte differentiation in vitro.
      These findings provide evidence for engraftment of multipotent stem cells in our
      patient with B-SCID. Furthermore, the failure of B-lymphocyte reconstitution
      cannot be explained by lack of donor-type B-lymphocyte progenitors. Donor-type B
      lymphopoiesis and myelopoiesis are prevented by an unidentified mechanism.

PMID- 7524744
TI  - Potential benefit of recombinant human granulocyte colony-stimulating factor
      mobilized peripheral blood stem cells for allogeneic transplantation.

PMID- 7524745
TI  - Direct comparison by limiting dilution analysis of long-term culture-initiating
      cells in human bone marrow, umbilical cord blood, and blood stem cells.
AB  - Limiting-dilution analysis of long-term culture-initiating cells (LTCIC) is a
      quantitative method of estimating hematopoietic stem cell activity in clinical
      samples. We compared the numbers of LTCIC in bone marrow (BM), umbilical cord
      blood, and blood progenitor cells (obtained from patients with solid tumors at
      leukapheresis after mobilization with induction chemotherapy and filgrastim
      administration), using a two-stage long-term culture system and a limiting
      dilution technique, scoring cobblestone areas of greater than 15 hematopoietic
      cells weekly for up to 8 weeks. Samples were obtained from 30 normal BMs, 20
      human umbilical cords, and 32 leukapheresis products. Direct comparison of LTCIC
      in the three sources showed that the median proportions of cells generating
      hematopoietic foci from unfractionated mononuclear cells at 5 and 8 weeks,
      respectively, were 1:13,314 and 1:33,949 for BM, 1:12,506 and 1:34,546 for
      umbilical cord blood, and 1:10,302 and 1:12,891 for leukapheresis product. The
      estimated proportions of LTCIC from unfractionated mononuclear cells and CD34+
      cells were similar in experiments with leukapheresis product. Leukapheresis
      product was superior to umbilical cord blood and cord blood to BM at 5 and 8
      weeks of culture (P = .01). In two-stage long-term cultures, more colonies per
      flask and CD34+ cells were found in assays of leukapheresis product than in BM or
      umbilical cord blood cultures (P = .0005). Results obtained by this simplified
      limiting-dilution analysis correlated well with standard long-term cultures and
      can be used as a measure of the stem cell population. These data suggest that the
      incidence of putative stem cells in leukapheresis product and umbilical cord
      blood are at least comparable with that of BM.

PMID- 7524746
TI  - Long-term generation of human mast cells in serum-free cultures of CD34+ cord
      blood cells stimulated with stem cell factor and interleukin-3.
AB  - The generation of murine mast cells is supported by several cytokines, and mast
      cell lines are frequently established in long-term cultures of normal murine
      marrow cells. In contrast, growth of human mast cells was initially dependent on
      coculture with murine fibroblasts. The growth factor produced by murine
      fibroblasts and required to observe differentiation of human mast cells is
      attributable in part to stem cell factor (SCF). However, other factors are likely
      involved. We have previously shown that the combination of SCF and interleukin-3
      (IL-3) efficiently sustains proliferation and differentiation of colony-forming
      cells (CFCs) from pre-CFC enriched from human umbilical cord blood by CD34+
      selection. With periodic medium changes and the addition of fresh growth factors,
      five consecutive cultures of different cord blood samples gave rise to
      differentiated cells and CFCs for more than 2 months. Although differentiated
      cells continued to be generated for more than 5 months, CFCs were no longer
      detectable by day 50 of culture. The cells have the morphology of immature mast
      cells, are Toluidine blue positive, are karyotypically normal, are CD33+, CD34-,
      CD45+, c-kit-, and c-fms-, and die in the absence of either SCF or IL-3. These
      cells do not form colonies in semisolid culture and are propagated in liquid
      culture stimulated with SCF and IL-3 at a seeding concentration of no less than
      10(4) cells/mL. At refeedings, the cultures contain a high number (> 50%) of dead
      cells and have a doubling time ranging from 5 to 12 days. This suggests that
      subsets of the cell population die because of a requirement for a growth factor
      other than SCF or IL-3. These results indicate that the combination of cord blood
      progenitor and stem cells, plus a cocktail of growth factors including SCF and IL
      3, is capable with high efficiency of giving rise in serum-deprived culture to
      human mast cells that behave like factor-dependent cell lines. These cells may
      represent a useful tool for studies of human mast cell differentiation and
      leukemia.

PMID- 7524747
TI  - Possible mechanisms accounting for the growth factor independence of
      hematopoietic progenitors from umbilical cord blood.
AB  - Hematopoietic progenitors obtained from the bone marrow of healthy adults fail to
      undergo clonogenic maturation in vitro if a source of hematopoietic growth
      factors is not included in the culture dishes. In contrast, a fraction of
      similarly purified progenitors obtained from umbilical cord blood undergo
      clonogenic maturation even in the absence of added growth factors. We postulated
      that production of hematopoietic growth factors within the culture dishes
      containing the progenitors of umbilical cord blood origin might be responsible.
      We postulated further, that this production might be by non-progenitor cells co
      plated along with the progenitors, or alternatively by CD34+ cells themselves, or
      by cells clonally derived from CD34+ cells. To test these possibilities we first
      assessed the effect of including in the cultures neutralizing antibody directed
      against various growth factors. Inclusion of anti-granulocyte macrophage colony
      stimulating factor (GM-CSF) and anti-interleukin-3 (IL-3) (but not anti-IL-2)
      significantly reduced the growth factor independence of cord blood progenitors (P
      < .005 and P < .01). Inclusion of both anti-GM-CSF and anti-IL-3 almost
      completely ablated the spontaneous colony growth (P < .001). Inclusion of IL-10
      also reduced, in a concentration-dependent fashion, the spontaneous generation of
      umbilical cord blood-derived colonies. Transcripts for GM-CSF and IL-3 were
      detected, by reverse transcriptase-polymerase chain reaction (RT-PCR), in the
      CD34+ cells from cord blood and from adult marrow. When plated without added
      growth factors, however, the CD34+ cells of adult marrow origin failed to produce
      colonies, whereas 6% of cord blood CD34+ cells similarly cultured did so. When
      these growth factor independent colonies were plucked from culture, transcripts
      for GM-CSF and IL-3 were identified in all. We conclude that production of GM-CSF
      and IL-3 occurs within culture dishes containing hematopoietic progenitors of
      umbilical cord origin, and that this explains some of their apparently unique
      features of in vitro growth.

PMID- 7524748
TI  - Localization of ligands for L-selectin in mouse peripheral lymph node high
      endothelial cells by colloidal gold conjugates.
AB  - L-selectin, a Ca(2+)-dependent lectin-like receptor, mediates lymphocyte
      attachment to high endothelial venules (HEV) of peripheral lymph nodes (PLN)
      during the process of lymphocyte homing. Two endothelial-derived ligands for L
      selectin, known as GlyCAM-1 (Sgp50) and CD34 (Sgp90), have been identified by
      affinity precipitation of lymph node extracts with a chimeric molecule that
      combines the extracellular domains of L-selectin with the human IgG1 Fc region (L
      selectin-IgG) (J Cell Biol 110:2221, 1990). Here, using a histologic probe based
      on colloidal gold conjugated to L-selectin-IgG (LS-Ig), we performed morphologic
      mapping of the HEV ligands in PLN at both the light and electron microscopic
      levels. With a postembedding labeling method, intense LS-Ig-gold staining of PLN
      HEV was observed, while the HEV of Peyer's patches (PP) were negative. The
      specificity of LS-Ig-gold staining was established by pretreatment of sections
      with sialidase and coincubation of sections with EGTA, fucoidin, or L-selectin
      IgG itself. In ultrastructural studies of high endothelial cells(HEC), gold
      particles were bound to the trans-Golgi network(TGN) and to peripheral vesicles
      in the cytoplasm. Gold labeling was also detected in a patchy distribution on the
      entire luminal vascular surface of HEC. Although the perivascular fibroreticular
      sheath of HEV was frequently labeled limited labeling was observed on the
      basolateral surfaces of the HEC. In most cases, the HEC membrane surrounding
      migrating lymphocytes was negative. These results show that L-selectin ligands
      pass through the Golgi apparatus during their biosynthesis, are stored in
      secretory granules, and are expressed on the vascular luminal surface of the HEC.
      A polyclonal antiserum to GlyCAM-1 intensely stained intracellular organelles in
      the biosynthetic pathway including cytoplasmic vesicles, but failed to stain the
      cell surface of HEC. Given its presence in serum as a soluble factor, GlyCAM-1 is
      likely to be a secretory product.

PMID- 7524749
TI  - Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of
      activated cytotoxic T cells with preference for mucosa-associated lymphoid tissue
      localization.
AB  - T-cell non-Hodgkin's lymphomas can be considered the neoplastic equivalents of
      immunologically functional, site-restricted T lymphocytes. Little is known about
      the occurrence and clinical behavior of T-cell lymphomas that are the neoplastic
      equivalents of different functional T-cell subsets. Here, we investigated the
      prevalence, preferential site, immunophenotype, and clinical behavior of the
      neoplastic equivalents of activated cytotoxic T cells (CTLs) in a group of 140
      nodal and extranodal T-cell lymphomas. Activated CTLs were shown
      immunohistochemically with a monoclonal antibody against granzyme B, a major
      constituent of the cytotoxic granules of activated T cells. Granzyme B-positive T
      cell lymphomas were mainly found in mucosa-associated lymphoid tissue (MALT;
      nose, 63% of the cases; gastrointestinal tract, 46%; and lung, 33%). Granzyme B
      positive cases with primary localization in MALT were more often associated with
      angioinvasion (P = .005), necrosis (P = .002), and histologic characteristics of
      celiac disease in adjacent mucosa not involved with lymphoma. Eosinophilia was
      more often observed in granzyme B-negative cases (P = .03). Most cases belonged
      to the pleomorphic medium- and large-cell group of the Kiel classification. CD30
      expression was more often found in granzyme B-positive lymphomas of MALT (P =
      .04), whereas CD56 expression was exclusively found in nasal granzyme B-positive
      lymphomas. Immunophenotypically, most of the cases should be considered as
      neoplastic equivalents of activated CTLs based on the presence of T-cell markers
      on tumor cells. In two cases of nasal lymphoma, tumor cells probably were the
      neoplastic counterparts of natural killer cells. The prognosis of the granzyme B
      positive gastrointestinal T-cell lymphomas was poor but did not differ from
      granzyme B-negative gastrointestinal T-cell lymphomas. This indicates that, in
      peripheral T-cell lymphomas, site of origin is more important as a prognostic
      parameter than derivation of activated CTLs.

PMID- 7524750
TI  - The human cardiac mast cell: localization, isolation, phenotype, and functional
      characterization.
AB  - We have isolated and characterized the human cardiac mast cell (CMC) and compared
      this novel mast cell (MC type with MC obtained from uterus, skin, and lung. Heart
      tissue was obtained from 14 patients with cardiomyopathy (CMP, heart
      transplantation). CMC were isolated by enzymatic digestion using collagenase,
      pronase-E, hyaluronidase, and DNAse. Substantial amounts of CMC (0.5% to 1.5% of
      isolated cells) were found in the atrial appendages but not in ventricular
      digests or other sites of the heart (< 0.1%). In situ staining of atrial tissue
      revealed the presence of CMC in the myocardium (2.16 +/- 0.7 MC/mm2), endocardium
      (2.24 +/- 0.9 MC/mm2), and epicardium. As assessed by combined toluidine
      blue/immunofluorescence staining with monoclonal antibodies (MoAbs), isolated CMC
      expressed surface IgE, the receptor for stem cell factor (c-kit receptor/CD117),
      the p24 antigen (CD9), the Pgp-1 homing receptor (CD44), the pan leukocyte
      antigen (CD45), and the ICAM-1 antigen (CD54). CMC were not recognized by MoAbs
      to lymphocyte function associated antigen 2 (LFA-2; CD2), T-cell receptor (TcR;
      CD3), T4 antigen (CD4), LFA-1 alpha-chain (CD11a), C3biR alpha-chain (CD11b), CR4
      alpha-chain (CD11c), LPS-R related Ag (CD14), 3-FAL/x-hapten (CD15), Fc gamma
      RIII (CD16), lactosylceramid (CDw17), the B-cell antigen CD19, or CR1 (CD35). In
      situ expression of leukocyte antigens on CMC was demonstrable by indirect
      immunoperoxidase staining technique and double-labeling immunohistochemistry.
      Almost all CMC (90%) reacted with MoAbs against tryptase and chymase and thus
      were MCTC. Cardiac mast cells were also stained by the heparin-binding dye
      Berberine sulfate and expressed measurable amounts of histamine (4.6 +/- 1.4 pg
      per cell). Cross linking of either IgE receptor or SCF receptor (c-kit) on CMC
      resulted in histamine secretion (non-specific release: < 6% of total histamine,
      alpha IgE induced: 12% to 52%; SCF-induced release: 9% to 18%), whereas neither
      substance P (a skin MC agonist) nor the basophil agonist FMLP showed an effect on
      CMC. Together, the CMC is an MCTC primarily located in the appendage of the
      atrium. This novel type of MC exhibits surface membrane antigen and functional
      properties similar to those of lung and uterus MC.

PMID- 7524751
TI  - Granulocyte colony-stimulating factor administration to healthy volunteers:
      analysis of the immediate activating effects on circulating neutrophils.
AB  - In four healthy volunteers, we analyzed in detail the immediate in vivo effects
      on circulating neutrophils of subcutaneous administration of 300 micrograms of
      granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed
      by measurement of degranulation. Mobilization of secretory vesicles was shown by
      a decrease in leukocyte alkaline phosphatase content of the circulating
      neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be
      upregulated from an intracellular pool that we identified by immunoelectron
      microscopy as secretory vesicles. Intravascular release of specific granules was
      shown by increased plasma levels of lactoferrin and by upregulation of the
      expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement
      of fourfold elevated plasma levels of elastase, bound to its physiologic
      inhibitor alpha 1-antitrypsin, indicated mobilization of azurophil granules.
      However, no expression of CD63, a marker of azurophil granules, was observed on
      circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and
      specific granules could be mimicked in whole blood cultures in vitro, in contrast
      to release of azurophil granules. Therefore, we postulate that the most activated
      neutrophils leave the circulation, as observed shortly postinjection, and undergo
      subsequent stimulation in the endothelial microenvironment, resulting in
      mobilization of azurophil granules. Our data demonstrate that G-CSF should be
      regarded as a potent immediate activator of neutrophils in vivo.

PMID- 7524752
TI  - Persistence of affected T lymphocytes in long-term clinical remission in
      paroxysmal nocturnal hemoglobinuria.
AB  - Long-term clinical remission of more than 10 years is rarely seen in paroxysmal
      nocturnal hemoglobinuria (PNH). Affected blood cells in PNH lack
      glycosylphosphatidylinositol (GPI)-anchored membrane proteins such as decay
      accelerating factor (DAF) and CD59. We performed a flow cytometric analysis of
      circulating blood cells obtained from two patients with PNH who had been in
      clinical remission for more than 10 and 25 years, respectively. Affected cells
      with the PNH phenotype were demonstrated only among T-lymphocytes. Persistent
      affected T cells were negative for the CD52 protein only, this protein being a
      GPI-anchored lymphocyte marker without complement regulatory activity. The
      persistence of the affected T cells may be explained either by an inherently long
      life span after the disappearance of the PNH stem cell or by insidious production
      at a subclinical level by affected stem cell. In either event, detection of
      affected T cells, especially CD52-negative T cells, may be useful for the
      evaluation of long-term clinical remission in PNH.

PMID- 7524753
TI  - Successful engraftment of T-cell-depleted haploidentical "three-loci"
      incompatible transplants in leukemia patients by addition of recombinant human
      granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells
      to bone marrow inoculum.
AB  - Patients who undergo transplantation with haploidentical "three-loci" mismatched
      T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome
      the host-versus-graft barrier, we increased the size of the graft inoculum, which
      has been shown to be a major factor in controlling both immune rejection and stem
      cell competition in murine models. Seventeen patients (mean age, 23.2 years;
      range, 6 to 51 years) with end-stage chemoresistant leukemia were received
      transplants of a combination of BM with recombinant human granulocyte colony
      stimulating factor-mobilized peripheral blood progenitor cells from HLA
      haploidentical "three-loci" incompatible family members. The average
      concentration of colony-forming unit-granulocyte-macrophage in the final inoculum
      was sevenfold to 10-fold greater than that found in BM alone. The sole graft
      versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft
      by the soybean agglutination and E-rosetting technique. The conditioning regimen
      included total body irradiation in a single fraction at a fast dose rate,
      antithymocyte globulin, cyclophosphamide and thiotepa to provide both
      immunosuppression and myeloablation. One patient rejected the graft and the other
      16 had early and sustained full donor-type engraftment. One patient who received
      a much greater quantity of T lymphocytes than any other patient died from grade
      IV acute GVHD. There were no other cases of GVHD > or = grade II. Nine patients
      died from transplant-related toxicity, 2 relapsed, and 6 patients are alive and
      event-free at a median follow-up of 230 days (range, 100 to 485 days). Our
      results show that a highly immunosuppressive and myeloablative conditioning
      followed by transplantation of a large number of stem cells depleted of T
      lymphocytes by soybean agglutination and E-rosetting technique has made
      transplantation of three HLA-antigen disparate grafts possible, with only rare
      cases of GVHD.

PMID- 7524754
TI  - Increased consumption of antithrombin III in patients receiving granulocyte
      macrophage colony-stimulating factor after bone marrow transplantation.

PMID- 7524755
TI  - Histiocytes and histiocytosis.
AB  - The term histiocyte refers to cells of either the macrophage or Langerhans cell
      lineages. The histiocytic disorders are characterized by the proliferation of
      cells of these lineages. With recent advances in knowledge of the developmental
      biology of histiocytic cells, it is now possible to formulate a reasonable
      catalogue of histiocytic diseases based on ultra-structural and phenotypic
      markers of cellular origins and molecular or chromosomal markers of malignancy.
      The catalogue includes the following groups of diseases. Nonmalignant reactive
      macrophage disorders include (1) macrophage storage diseases, (2) several benign
      proliferative macrophage disorders that predominantly involve skin and bone, and
      (3) several hemophagocytic syndromes that vary from indolent and benign to
      fulminant and fatal. In some of the latter disorders, viruses have been
      identified as the inciting stimulus. The malignant macrophage disorders include
      (1) acute monocytic leukemia and (2) chronic myelomonocytic leukemia. A rare
      disorder that gave rise to a permanent cell line with an anomaly of chromosomal
      segment 5q35 may also be an example of a histiocytic malignancy. The existence of
      a separate category of true histiocytic lymphoma of macrophage type is uncertain.
      Reactive Langerhans cell disorders include (1) congenital self-healing
      histiocytosis, (2) the many variants of eosinophilic granuloma, and (3) a related
      disorder designated as relapsing Langerhans cell histiocytosis that is
      characterized by a relapsing course and infiltration of bone and soft tissues by
      Langerhans cells. Presumptively neoplastic diseases of Langerhans and dendritic
      cells include (1) progressive Langerhans cell histiocytosis, a disease with
      prominent involvement of blood and BM as well as skin and viscera; (2) Langerhans
      cell lymphoma, and (3) dendritic cell lymphoma. However, clonality as a marker of
      malignancy has not been proven in these disorders.

PMID- 7524756
TI  - Increased gene transfer into human hematopoietic progenitor cells by extended in
      vitro exposure to a pseudotyped retroviral vector.
AB  - Retroviral-mediated gene transfer is the most attractive modality for gene
      transfer into hematopoietic stem cells. However, transduction efficiency has been
      low using amphotropic Moloney murine leukemia virus (MoMLV) vectors. In this
      study, we investigated modifications of gene transfer using amphotropic MoMLV
      vectors in cell-free supernatant for their ability to increase the currently low
      transduction of both committed hematopoietic progenitors, granulocyte-macrophage
      colony-forming units (CFU-GMs), and their precursors, long-term culture
      initiating cells (LTC-IC). First, based on the observation that bone marrow cells
      express more gibbon ape leukemia virus (GALV) receptor (Glvr-1) than amphotropic
      receptor (Ram-1), PG13/LN, which is a MoMLV vector pseudotyped with the GALV
      envelope, was compared with the analogous amphotropic envelope vector (PA317/LN).
      Second, progenitor cell transduction efficiency was compared between CD34
      enriched and nonenriched progenitor populations. Third, the duration of
      transduction in vitro was extended to increase the proportion of progenitor cells
      that entered cell cycle and could thereby integrate vector cDNA. In 20
      experiments, 1 x 10(6) marrow or peripheral blood mononuclear cells (PBMCs)/mL
      were exposed to identical titers of pseudotyped PG13/LN vector or PA317/LN vector
      in the presence of recombinant human interleukin-1 (IL-1), IL-3, IL-6, and stem
      cell factor (SCF; c-kit ligand) for 5 days. 50% of fresh vector supernatant was
      refed daily. Hematopoietic progenitor cells as measured by G418-resistant
      granulomonocytic colony (CFU-GM) formation were transduced more effectively with
      PG13/LN (19.35%) than with PA317/LN (11.5%, P = .012). In 11 further experiments,
      enrichment of CD34 antigen positive cells significantly improved gene transfer
      from 13.9% G418-resistant CFU-GM in nonenriched to 24.9% in CD34-enriched
      progenitor cells (P < .01). To analyze gene transfer after extended growth factor
      supported long-term culture, 1 x 10(6) marrow cells/mL were cultured with IL-1,
      IL-3, IL-6, and SCF (50 ng/mL each) for 1, 2, and 3 weeks. Fifty percent of
      PG13/LN supernatant with growth factors was refed on 5 days per week. Five
      percent of marrow CFU-GM and 67% of LTC-IC were G418 resistant at 1 week (n = 4),
      60% of CFU-GM and 100% of LTC-IC were resistant at 2 weeks (n = 2) and 74% of CFU
      GM (n = 4) and 82% of LTC-IC (n = 2) were resistant at three weeks.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7524758
TI  - Identification of CRKL as the constitutively phosphorylated 39-kD tyrosine
      phosphoprotein in chronic myelogenous leukemia cells.
AB  - Chronic myelogenous leukemia (CML) is characterized by the presence of the
      Philadelphia (Ph) chromosome in clonally derived hematopoietic precursors and
      their progeny. The Ph chromosome arises from a translocation that deregulates the
      c-ABL protein tyrosine kinase, giving it transforming potential and increased
      kinase activity. We observed a unique 39-kD tyrosine phosphoprotein (pp39),
      previously reported in blastic CML cell lines, in neutrophils from 50 cases of
      chronic phase CML. This protein was prominently and constitutively tyrosine
      phosphorylated in CML neutrophils and was not phosphorylated in normal
      neutrophils. Stimulation of normal neutrophils with cytokines and agonists did
      not induce tyrosine phosphorylation of proteins migrating in the region of pp39,
      and the phosphorylation state of pp39 in CML neutrophils was not affected by
      kinase inhibitors known to downregulate the ABL kinase. The pp39 was not
      phosphorylated in hematopoietic cells from healthy donors or from patients with
      Ph chromosome-negative myeloproliferative disorders. Using micro amino acid
      sequencing of purified preparations of pp39, we identified pp39 as CRKL protein,
      which is consistent with recent immunologic studies in the blastic K562 cell
      line. Immunoblotting with anti-CRKL antibodies showed the presence of CRKL
      protein in CML cells and cell lines as well as in antiphosphotyrosine
      immunoprecipitates from CML cells. Our results suggest that pp39 CRKL in CML
      neutrophils may be stably tyrosine-phosphorylated by the BCR/ABL kinase at an
      early stage of myeloid differentiation when the ABL kinase is active. CRK, CRKL,
      and other SH2 (SRC homology domain)/SH3-containing proteins function as adaptor
      molecules in nonreceptor tyrosine kinase signalling pathways. Although the CRKL
      protein is present in normal neutrophils, it is not tyrosine-phosphorylated, and
      the inability to induce such phosphorylation in normal neutrophils suggests a
      special role of this phosphoprotein in the pathogenesis of CML. Constitutive
      phosphorylation of CRKL is unique to CML, indicating that it may be a useful
      target for therapeutic intervention.

PMID- 7524757
TI  - Maintenance of transplantation potential in ex vivo expanded CD34(+)-selected
      human peripheral blood progenitor cells.
AB  - CD34(+)-selected hematopoietic progenitor cells are being increasingly used for
      autotransplantation, and recent evidence indicates that these cells can be
      expanded ex vivo. Of 15 patients with solid tumors undergoing a phase I/II
      clinical trial using CD34(+)-selected peripheral blood progenitor cells (PBPCs)
      after high-dose chemotherapy, we analyzed the frequency of long-term culture
      initiating cells (LTCIC) as a measure of transplantation potential before and
      after ex vivo expansion of CD34+ cells. PBPCs were mobilized by combination
      chemotherapy and granulocyte colony-stimulating factor (G-CSF). The original
      unseparated leukapheresis preparations, the CD34(+)-enriched transplants, as well
      as nonabsorbed fractions eluting from the CD34 immunoaffinity columns (Ceprate;
      CellPro, Bothell, WA) were monitored for their capacity to repopulate irradiated
      allogeneic stroma in human long-term bone marrow cultures. We found preservation
      of more than three quarters of fully functional LTCIC in the CD34(+)-selected
      fractions. Quantitation of LTCIC by limiting dilution analysis showed a 53-fold
      enrichment of LTCIC from 1/9,075 in the unseparated cells to an incidence of
      1/169 in the CD34+ fractions. Thus, in a single apheresis, it was possible to
      harvest a median of 1.65 x 10(4) LTCIC per kg body weight (range, 0.71 to 3.72).
      In addition, in six patients, large-scale ex vivo expansions were performed using
      a five-factor cytokine combination consisting of stem cell factor (SCF),
      interleukin-1 (IL-1), IL-3, IL-6, and erythropoietin (EPO), previously shown to
      expand committed progenitor cells. LTCIC were preserved, but not expanded during
      the culture period. Optimization of ex vivo expansion growth factor requirements
      using limiting dilution assays for LTCIC estimation indicated that the five
      factor combination using SCF, IL-1, IL-3, IL-6, and EPO together with autologous
      plasma was the most reliable combination securing both high progenitor yield and,
      at the same time, optimal preservation of LTCIC. Our data suggest that ex vivo
      expanded CD34+ PBPCs might be able to allow long-term reconstitution of
      hematopoiesis.

PMID- 7524759
TI  - Effects of in vivo recombinant methionyl human granulocyte colony-stimulating
      factor on the neutrophil response and peripheral blood colony-forming cells in
      healthy young and elderly adult volunteers.
AB  - Recombinant granulocyte colony stimulating factor (G-CSF) was administered daily
      for 14 days to healthy young (Y) (20 to 30 years) and elderly (O) (70 to 80
      years) volunteers to evaluate the effects of age on the neutrophil
      (polymorphonuclear leukocytes, PMN) responses. Thirty-eight volunteers were
      randomized to receive 0 micrograms, 30 micrograms, or 300 micrograms per day.
      Baseline neutrophil counts (ANC), peak ANCs, and the rate of attaining the peak
      ANC were similar in both age groups at both doses. The peak ANC was increased 5
      fold at 30 micrograms and 15-fold at 300 micrograms in both the young and
      elderly. Daily tests of PMN function, as measured by an automated
      chemiluminescence system, showed nearly identical responses to several agonists
      for both age groups. Marrow proliferative activity as reflected by the percentage
      of cells in the marrow neutrophil mitotic pool also increased similarly for both
      age groups at both doses. In contrast, there was an age-related change in blood
      colony formation as measured by the blood CFU-GM assay. Compared with controls at
      the 30 micrograms dose, mean colony formation was increased 2-fold in the young
      versus no change in the elderly and at the 300 micrograms dose 24-fold in the
      young versus 12-fold in the elderly. These studies indicate that neutrophil
      responses to rhG-CSF are equivalent in healthy young and elderly volunteers but
      the mobilization of progenitor cells, as measured by the CFU-GM assay appears to
      differ substantially.

PMID- 7524760
TI  - A comparative study of the phenotype and proliferative capacity of peripheral
      blood (PB) CD34+ cells mobilized by four different protocols and those of steady
      phase PB and bone marrow CD34+ cells.
AB  - Peripheral blood (PB) CD34+ cells from four commonly used mobilization protocols
      were studied to compare their phenotype and proliferative capacity with steady
      state PB or bone marrow (BM) CD34+ cells. Mobilized PB CD34+ cells were collected
      during hematopoietic recovery after myelosuppressive chemotherapy with or without
      granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony
      stimulating factor (G-CSF) or during G-CSF administration alone. The expression
      of activation and lineage-associated markers and c-kit gene product were studied
      by flow cytometry. Proliferative capacity was measured by generation of nascent
      myeloid progenitor cells (granulocyte-macrophage colony-stimulating factor; CFU
      GM) and nucleated cells in a stroma-free liquid culture stimulated by a
      combination of six hematopoietic growth factors (interleukin-1 (IL-1), IL-3, IL
      6, GM-CSF, G-CSF, and stem cell factor). G-CSF-mobilized CD34+ cells have the
      highest percentage of CD38- cells (P < .0081), but otherwise, CD34+ cells from
      different mobilization protocols were similar to one another in their phenotype
      and proliferative capacity. The spectrum of primitive and mature myeloid
      progenitors in mobilized PB CD34+ cells was similar to their steady-state
      counterparts, but the percentages of CD34+ cells expressing CD10 or CD19 were
      lower (P < .0028). Although steady-state PB and chemotherapy-mobilized CD34+
      cells generated fewer CFU-GM at day 21 than G-CSF-mobilized and steady-state BM
      CD34+ cells (P < .0449), the generation of nucleated cells and CFU-GM were
      otherwise comparable. The presence of increased or comparable numbers of
      hematopoietic progenitors within PB collections with equivalent proliferative
      capacity to BM CD34+ cells is not unexpected given the rapid and complete
      hematopoietic reconstitution observed with mobilized PB. However, all four types
      of mobilized PB CD34+ cells are different from steady-state BM CD34+ cells in
      that they express less c-kit (P < .0002) and CD71 (P < .04) and retain less
      rhodamine 123 (P < .0001). These observations are novel and suggest that
      different mobilization protocols may act via similar pathways involving the down
      regulation of c-kit and may be independent of cell-cycle status.

PMID- 7524761
TI  - All-trans retinoic acid directly inhibits granulocyte colony-stimulating factor
      induced proliferation of CD34+ human hematopoietic progenitor cells.
AB  - In this study we examine the effects of retinoids on purified CD34+ human
      hematopoietic progenitor cells. All-trans retinoic acid inhibited granulocyte
      colony-stimulating factor (G-CSF)-induced proliferation of CD34+ cells in short
      term liquid cultures in a dose-dependent fashion with maximal inhibition of 72%
      at a concentration of retinoic acid of 1 mumol/L. Although no significant effects
      were observed on granulocyte-macrophage CSF (GM-CSF)--interleukin-3--or stem cell
      factor (SCF)-induced proliferation, the combinations of G-CSF and each of these
      cytokines were all inhibited. Moreover, retinol (3 mumol/L) and chylomicron
      remnant retinyl esters (0.1 mumol/L) in concentrations normally found in human
      plasma also had inhibitory effects. Single-cell experiments showed that the
      effects of retinoic acid were directly mediated. Retinoids also significantly
      inhibited G-CSF-induced colony formation in semisolid medium, with 88% inhibition
      observed at a concentration of retinoic acid of 1 mumol/L. However, we did not
      observe any effects of retinoic acid on G-CSF-induced differentiation as assessed
      by morphology and flowcytometry. Similar to previous findings using total bone
      marrow mononuclear cells, we observed a stimulation of GM-CSF-induced colony
      formation after 14 days. We also observed a stimulatory effect of low doses of
      retinoic acid (30 nmol/L) on blast-cell colony formation on stromal cell layers.
      Taken together, the data indicate that vitamin A present in human plasma has
      inhibitory as well as stimulatory effects on myelopoiesis.

PMID- 7524764
TI  - Anti-CD38-blocked ricin: an immunotoxin for the treatment of multiple myeloma.
AB  - We report the development of a potent anti-CD38 immunotoxin capable of killing
      human myeloma and lymphoma cell lines. The immunotoxin is composed of an anti
      CD38 antibody HB7 conjugated to a chemically modified ricin molecule wherein the
      binding sites of the B chain have been blocked by covalent attachment of affinity
      ligands (blocked ricin). Conjugation of blocked ricin to the HB7 antibody has
      minimal effect on the apparent affinity of the antibody and no effect on the
      ribosome-inactivating activity of the ricin A-chain moiety. Four to six logs of
      CD38+ tumor cell line kill was achieved at concentrations of HB7-blocked ricin in
      the range of 0.1 to 3 nmol/L. Low level of toxicity for normal bone marrow (BM)
      granulocyte-macrophage colony-forming units (CFU-GM), burst-forming units
      erythroid (BFU-E), colony-forming units-granulocyte/erythroid/monocyte/macrophage
      (CFU-GEMM) cells was observed. Greater than two logs of CD38+ multiple myeloma
      cells were depleted from a 10-fold excess of normal BM mononuclear cells (BMMCs)
      after an exposure to HB7-blocked ricin under conditions (0.3 nmol/L) that were
      not very toxic for the normal BM precursors. HB7-blocked ricin was tested for its
      ability to inhibit protein synthesis in fresh patients' multiple myeloma cells
      and in normal BMMCs isolated from two healthy volunteers; tumor cells from four
      of five patients were 100-fold to 500-fold more sensitive to the inhibitory
      effect of HB7-blocked ricin than the normal BM cells. HB7 antibody does not
      activate normal resting peripheral blood lymphocytes, and HB7-blocked ricin is
      not cytotoxic toward these cells at concentrations of up to 1 nmol/L. The potent
      killing of antigen-bearing tumor cells coupled with a lack of effects on
      peripheral blood T cells or on hematopoietic progenitor cells suggests that HB7
      blocked ricin may have clinical utility for the in vivo or in vitro purging of
      human multiple myeloma cells.

PMID- 7524762
TI  - Steel factor affects SCL expression during normal erythroid differentiation.
AB  - Steel factor is one of the growth factors that controls the proliferation and
      differentiation of hematopoietic cells and SCL, also known as Tcl-5 or Tal-1, is
      a transcription factor involved in erythropoiesis. In this report, we studied the
      role of SCL in the proliferation of human peripheral blood burst-forming unit
      erythroid (BFU-E) and the effects of Steel factor on SCL expression in
      proliferating erythroid cells. BFU-E-derived colonies increase progressively in
      size, as determined by cell number, from day 7 to day 14 of culture, with the
      greatest increase in colony size (10-fold expansion) occurring between day 7 and
      day 10. SCL protein levels in BFU-E-derived cells were highest in day 7 cells and
      decreased progressively from day 7 to day 14 of culture, suggesting an
      association of SCL with erythroid proliferation. In contrast, SCL mRNA levels did
      not decrease significantly between day 7 and day 14 cells, suggesting that
      posttranscriptional mechanisms are largely responsible for the decrease in SCL
      protein observed. The role of SCL in Steel factor-induced erythroid proliferation
      was then examined. In BFU-E-derived colonies cultured with Steel factor, colony
      size was significantly increased compared to control. In day 7 and day 10
      erythroid precursors cultured with Steel factor, SCL protein was increased
      significantly compared to control. The increase in SCL protein levels in early
      erythroid precursors stimulated with Steel factor suggests one mechanism through
      which Steel factor may enhance normal erythroid proliferation. SCL mRNA levels
      assessed by Northern blot in day 7 cells did not increase significantly in
      response to Steel factor stimulation, suggesting that posttranscriptional
      mechanisms may also be important in the increase in SCL protein observed in
      response to Steel.

PMID- 7524763
TI  - Poor response of cultured mast cells derived from mi/mi mutant mice to nerve
      growth factor.
AB  - Decreased numbers of mast cells and abnormalities in the phenotype of mast cells
      are observed in the skin of mi/mi mutant mice. Recently, the mi locus was
      identified to encode a novel member of the basic-helix-loop-helix-leucine zipper
      protein family of transcription factors. Since nerve growth factor (NGF) has been
      reported to influence the proliferation and the phenotype of cultured mast cells
      (CMCs), we compared the effect of NGF between mi/mi and control normal (+/+)
      CMCs. Addition of NGF to the suboptimal dose of recombinant murine interleukin-3
      (rmIL-3) increased the plating efficiency of +/+ CMCs, but not of mi/mi CMCs.
      Although +/+ CMCs were berberine sulfate-negative when cultured with rmIL-3
      alone, +/+ CMCs became berberine sulfate-positive when cultured in the presence
      of both rmIL-3 and NGF, which suggests increased heparin content. In contrast,
      NGF did not influence the phenotype of mi/mi CMCs. +/+ CMCs significantly bound
      125I-NGF, but mi/mi CMCs did not, which suggests a defect of NGF receptors in
      mi/mi CMCs. Both p75 and p140 molecules are known to be involved in the formation
      of NGF receptors. Although the expression of p140 messenger (m)RNA was comparable
      between +/+ and mi/mi CMCs, the expression of p75 mRNA was significantly lower in
      mi/mi CMCs than in +/+ CMCs. Taken together, the poor response of mi/mi CMCs to
      NGF appeared to be attributable to the impaired transcription of the p75 gene.

PMID- 7524766
TI  - Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation
      via the CD40 antigen.
AB  - Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was
      examined in 43 patients. In this culture system, cells were stimulated by
      interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added
      in soluble form or were cross-linked via their Fc part using Fc gamma RII
      transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H
      thymidine incorporation in 14 cases and by the presence of metaphases in 42
      cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking
      of anti-CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation
      with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation;
      the addition of IL-4 further enhanced 3H-thymidine incorporation in 5 cases, but
      suppressed this phenomenon in 5 other cases. The CD40 system proved to be very
      effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients
      tested, we found clonal abnormalities in 8 cases (19%) and nonclonal
      abnormalities with involvement of one or two abnormal metaphases in another 7
      cases. The chromosomes most frequently involved in the abnormal karyotypes, both
      structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence
      activated cell-sorting analysis of the cultured cells, and by immunophenotypic
      analysis of metaphase spreads, T-cell growth could be excluded and the HCL
      lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for
      growing hairy cell leukemia cells.

PMID- 7524765
TI  - Anti-CD40 antibody binding modulates human multiple myeloma clonogenicity in
      vitro.
AB  - Ligand binding of the B-cell lineage antigen CD40 enhances growth and interleukin
      6 (IL-6) secretion in human B cells (the CD40/IL-6 loop). IL-6 has an autocrine
      and paracrine role in human multiple myeloma (MM) cell growth. With the use of
      the CD40 monoclonal antibody (MoAb) G28-5, we examined CD40 expression and the
      effect of CD40 binding on MM clonogenic colony (MCC) formation to characterize
      the IL-6/CD40 loop activity in MM. CD40 was expressed on plasmacytoid cells in 21
      of 28 plasma cell dyscrasia (PCD) bone marrow (BM) biopsies tested (10 of 14 MM,
      2 of 2 Waldenstrom's macroglobulinemia [WM], 2 of 2 plasma cell leukemia [PCL], 6
      of 8 monoclonal gammopathy of undetermined significance [MGUS], and 1 of 2
      primary amyloidosis [AL]). G28-5 binding increased MCCs by 35% to 150% in 11 of
      17 CD40+ PCD BM cultures, but did not affect MCC formation in CD40- specimens or
      normal BM colony forming units (CFU-GEMM, CFU-GM, BFU-E). Responsive cultures
      originated from BM of patients with MM (2 of 5 cases tested), WM (2 of 2), PCL (2
      of 2), and MGUS (5 of 6). CD40-responsiveness was not significantly inhibited by
      the presence of an anti-IL-6 MoAb (2 of 2 MGUS cultures tested), and did not
      correlate with the capacity to respond to IL-6 stimulation (n = 17, P > .05) or a
      detectable level of endogenous IL-6 (n = 15, P > .05). Additional studies were
      performed with PCD cell lines to characterize the interrelationship of CD40
      activation and IL-6 production. Fifty percent to greater than 95% of cells from
      the RPMI 8226 and ARH77 lines expressed CD40, whereas 6% of U266 cells were
      CD40+. For RPMI 8226, ARH-77, and U266 cells, the increased MCC formation after
      anti-CD40 stimulation was not affected by the presence of an anti-IL-6
      neutralizing MoAb and was not accompanied by detectable IL-6 secretion. There was
      no apparent increase in IL-6 mRNA transcription following G28-5 treatment of U266
      or RPMI 8226 cells. Our observations indicate that CD40 is expressed in a subset
      of human myeloma cells present in various PCDs. Cell-line studies suggest that
      the CD40+ myeloma cell may regulate MM clonogenic colony formation without
      activating the IL-6 pathway.

PMID- 7524767
TI  - Variation in fetal hemoglobin parameters and predicted hemoglobin S
      polymerization in sickle cell children in the first two years of life: Parisian
      Prospective Study on Sickle Cell Disease.
AB  - Intracellular hemoglobin S (HbS) polymerization is most likely to be the primary
      determinant of the clinical and biologic manifestations of sickle cell disease
      (SCD). Fetal hemoglobin (HbF) does not enter the HbS polymer and its
      intracellular expression in sickle erythrocytes inhibits polymerization. HbF
      levels, high at birth but decreasing thereafter, protect the newborn from the
      clinical manifestations of this hemoglobinopathy. We have measured the sequential
      changes in HbF, F reticulocytes, and F cells in the first 2 years of life in 25
      children with SCD and compared the results with those obtained in 30 normal
      children (AA). We have also calculated HbF per F cell (F/F cell), the
      preferential survival of F cells versus non-F cells, as measured by the ratio F
      cells versus F reticulocytes (FC/FR) and polymer tendency at 40% and 70% oxygen
      saturation. HbF levels decreased from about 80.4% +/- 4.0% at birth to 9.2% +/-
      2.9% at 24 months. During this time, we observed a regular decrease of the F
      reticulocytes and the F cells. The kinetics of the decline of F/F cell was
      comparable with the decline of HbF, rapid from birth (mean, 27.0 +/- 3.6 pg) to
      12 months of age (mean, 8.5 +/- 1.5 pg) and then slower from 12 to 24 months of
      age (mean, 6.2 +/- 1.0 pg) in the SCD children. In the AA children, the decrease
      in HbF, due to changes in both numbers of F cells and F/F cell, was more
      precipitous, reaching steady-state levels by 10 months of age. Calculated values
      for mean polymer tendency in the F-cell population showed that polymerization
      should begin to occur at 40% oxygen saturation at about 3 months and increase
      progressively with age, whereas polymerization at 70% oxygen saturation would not
      occur until about 24 months. These values correspond to HbF levels of 50.8% +/-
      10.8% and 9.2% +/- 2.9%, respectively, and F/F cell levels of 15.6 +/- 4.5 pg and
      6.2 +/- 1.0 pg, respectively. In the non--F-cell population, polymerization was
      expected at birth at both oxygen saturation values. Three individuals had
      significantly greater predicted polymerization tendency than the remainder of the
      group because of early decreases in HbF. These individuals in particular, the
      remainder of the cohort, as well as other recruited newborns, will be studied
      prospectively to ascertain the relationship among hematologic parameters, which
      determine polymerization tendency and the various clinical manifestations of SCD.

PMID- 7524769
TI  - Molecular mapping of the Cromer blood group Cra and Tca epitopes of decay
      accelerating factor: toward the use of recombinant antigens in immunohematology.
AB  - Cromer blood group antigens reside on the complement regulatory protein decay
      accelerating factor (DAF, CD55). This glycosyl-phosphatidylinositol-anchored
      glycoprotein is widely distributed, especially among cell types in contact with
      plasma. Numerous Cromer blood group antigens have been defined using
      alloantibodies induced by transfusion or pregnancy. However, few pairs of
      antithetical antigens have been described in this system, presumably because of
      the rarity of the low-frequency alleles. Analysis of polymerase chain reaction
      amplified genomic DNA showed that the Cr(a-) phenotype has a Ala193-->Pro
      substitution in short consensus repeat 4 (SCR4) of DAF, and the Tc(a-b+)
      phenotype has a Arg18-->Leu substitution in SCR1 of DAF. The locations of Cra and
      Tca epitopes were confirmed by analysis of Chinese hamster ovary cell
      transfectants expressing a Cr(a-) allele-specific transfectant and a chimeric
      protein containing only SCR1 of DAF, respectively. Overall, these studies further
      show the usefulness of an approach based on recombinant proteins in mapping blood
      group antigen epitopes and identifying blood group antibodies.

PMID- 7524768
TI  - Fetal hemoglobin induction by acetate, a product of butyrate catabolism.
AB  - Butyrate induces fetal hemoglobin (HbF) synthesis in cultures of erythroid
      progenitors, in primates, and in man. The mechanism by which this compound
      stimulates gamma-globin synthesis is unknown. In the course of butyrate
      catabolism, beta oxidation by mitochondrial enzymes results in the formation of
      two acetate molecules from each molecule of butyrate. Studies were performed to
      determine whether acetate itself induces HbF synthesis. In erythroid burst
      forming unit (BFU-E) cultures from normal persons, and individuals with sickle
      cell disease and umbilical-cord blood, dose-dependent increases in gamma-globin
      protein and gamma mRNA were consistently observed in response to increasing
      acetate concentrations. In BFU-E cultures from normal adults and patients with
      sickle cell disease, the ratio of gamma/gamma + beta mRNA increased twofold to
      fivefold in response to acetate, whereas the percentage of BFU-E progeny staining
      with an anti-gamma monoclonal antibody (MoAb) increased approximately twofold.
      Acetate-induced increases in gamma-gene expression were also noted in the progeny
      of umbilical cord blood BFU-E, although the magnitude of change in response to
      acetate was less because of a higher baseline of gamma-chain production. The
      effect of acetate on HbF induction in vivo was evaluated using transgenic mouse
      and primate models. A transgenic mouse bearing a 2.5-kb mu locus control region
      (mu LCR) cassette linked to a 3.3-kb A gamma gene displayed a near twofold
      increase in gamma mRNA during a 10-day infusion of sodium acetate at a dose of
      1.5 g/kg/d. Sodium acetate administration in baboons, in doses ranging from 1.5
      to 6 g/kg/d by continuous intravenous infusion, also resulted in the stimulation
      of gamma-globin synthesis, with the percentage of HbF-containing reticulocytes (F
      reticulocytes) approaching 30%. Surprisingly, a dose-response effect of acetate
      on HbF induction was not observed in the baboons, and HbF induction was not
      sustained with prolonged acetate administration. These results suggest that both
      two-carbon fatty acids (acetate) and four-carbon fatty acids (butyrate) stimulate
      synthesis of HbF in vivo.

PMID- 7524770
TI  - Alpha-Thalassemia and fetal hemoglobin.

PMID- 7524771
TI  - Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and
      rhG-CSF in the treatment of a child with severe chronic neutropenia.

PMID- 7524773
TI  - International Symposium on Thoracoscopic Sympathicotomy. Boras, Sweden, June 2-4,
      1993.

PMID- 7524772
TI  - Quantitative analysis of mutant p53 protein in breast tumor cytosols and study of
      its association with other biochemical prognostic indicators in breast cancer.
AB  - Breast tumors are thought to originate, grow, and metastasize in an environment
      which includes steroid hormone receptors, their cognate steroid ligands, and many
      gene products which are regulated by steroid hormone receptor-ligand complexes.
      In this paper we describe highly sensitive and quantitative immunofluorometric
      procedures for measuring three proteins that are candidate prognostic indicators
      in breast cancer, namely, the p53 tumor suppressor gene product, carcinoembryonic
      antigen (CEA), and prostate specific antigen (PSA). These proteins were
      quantified in over 950 cytosolic tumor extracts along with estrogen and
      progesterone receptors (ER, PR). Association analysis between all five
      biochemical parameters revealed strong negative associations between p53 and
      receptors and strong positive associations between CEA and receptors. Negative
      associations between p53 and CEA and between CEA and PSA were also found. These
      associations, not quantitatively studied in previous reports, are related to each
      other using a hypothetical model. The observed associations may further
      contribute to the understanding of the biology of breast tumors.

PMID- 7524775
TI  - Present and future trends in thoracoscopic sympathectomy.

PMID- 7524774
TI  - Thoracoscopic versus open supraclavicular upper dorsal sympathectomy: a
      prospective randomised trial.
AB  - The purpose of the present study was to compare the short term results of the
      "open" supraclavicular approach with the thoracoscopic access for T2-T4
      sympathetic ganglionectomy in patients with palmar hyperhidrosis. Patients were
      randomly allocated into two groups of 12 each, and were operated on: one by the
      open supraclavicular access; the other by the transthoracoscopic approach. The
      effect on palmar perspiration, operative data, postoperative complications and
      patients's satisfaction on short term follow up were examined. All operations
      achieved dry hands. Only two significant differences were observed: longer
      anaesthesia and poorer patient satisfaction in the thoracoscopic group one week
      after surgery (probably because a higher proportion of cases developed prolonged
      postoperative chest pain). Both techniques similarly achieve dry hands. The open
      method is not longer or more difficult, is possibly associated with less
      morbidity, and gives a higher subjective satisfaction.

PMID- 7524776
TI  - Thoracoscopic surgery of palmar hyperhidrosis.
AB  - New thoracoscopic methods have been reported to minimise the operative trauma
      after surgical treatment of primary hyperhidrosis of the palms. We therefore
      began with this minimally invasive technique for sympathetic ablation in 1990.
      Our first 81 patients presented here confirm earlier results of excellent
      effects, few complications and mild side-effects when treating palmar
      hyperhidrosis with thoracoscopic sympathectomy.

PMID- 7524777
TI  - Intraoperative anaesthetic management of hypoxaemia during transthoracic
      endoscopic sympathectomy.
AB  - OBJECTIVE: To present our experience and evaluate intraoperative arterial oxygen
      desaturation during anaesthesia for transthoracic endoscopic sympathectomy (TES).
      DESIGN: Prospective open study. SETTING: University Hospital in Israel. SUBJECTS:
      Consecutive series of patients (n = 210), suffering from upper limb
      hyperhidrosis, anaesthetised for TES. MAIN OUTCOME MEASURES: Peripheral oxygen
      saturation (SpO2), haemodynamic status, complications, postoperative pain (n =
      210) and arterial blood gases (n = 10). RESULTS: 407 TES; 195 bilateral, 17
      unilateral. Surgical time range 20-75 minutes. SpO2 decreased below 98% in 58
      patients. Sudden hypotension and bradycardia in two patients. The mean PaO2 was
      significantly (p = 0.03) decreased during two-lung ventilation (TLV), after
      reinflation of the right lung, compared with TLV after endobronchial intubation.
      There was no significant difference in mean PaO2 during one-lung ventilation of
      both lungs. Lowest PaO2 observed during one-lung ventilation was less than 13.3
      kPa in three sympathectomies. Postoperative pain, severe on awakening and mainly
      retrosternal, was relieved with i.v. opiates. CONCLUSION: Controlled ventilation
      with 100% inspired O2, SpO2 monitoring and one to two gentle manual ventilations
      when it decreases is the cornerstone of the management of hypoxaemia, a
      potentially serious complication of TES.

PMID- 7524779
TI  - Anaesthetic implications for transthoracic endoscopic sympathectomy.
AB  - Transthoracic endoscopic sympathectomy is now considered the treatment of choice
      for patients with upper limb hyperhidrosis requiring sympathetic ablation. This
      procedure requires the use of an endobronchial double lumen tube and subsequent
      one-lung anaesthesia, a technique that is associated with a number of potential
      problems. Full patient monitoring is thus required and includes pulse, ECG, non
      invasive blood pressure measurement, pulse oximetry, end-tidal carbon dioxide
      concentration and peak inspiratory airway pressure. We reviewed our anaesthetic
      technique and peri-operative complications in 26 patients, to assess patient
      safety. In our study hypoxaemia occurred commonly but was transient in all bar
      one case where re-expansion of the lung was required. Hypotension occurred at two
      stages of the procedure, but active intervention was not required, and two
      patients required underwater drainage of the pleural cavity for treatment of
      pneumothorax. With skilled anaesthetic personnel and adequate monitoring this
      procedure may be carried out safely.

PMID- 7524780
TI  - Total intravenous anaesthesia with single-lumen endotracheal intubation for
      thoracoscopic sympathectomy.
AB  - The aim of this paper was to discuss the stress applied to the circulatory and
      respiratory systems by the combination of general anaesthesia and thoracoscopic
      sympathectomy and to show the benefits of an intravenous anaesthetic technique
      together with a single-lumen endotracheal tube as a safe method of anaesthesia
      for this procedure. In a retrospective study, 125 cases of thoracoscopic
      sympathectomy were reviewed. The anaesthesia was a totally intravenous technique
      with propofol, alfentanil, and atracurium and a gas mixture of 40% oxygen in air.
      The degree of hypoxaemia during inflation of carbon dioxide into the thorax was
      assessed. The results showed that hypoxaemia caused no problems in any of the
      patients. Three patients with severe angina pectoris were also studied using the
      same anaesthetic technique and they showed marked haemodynamic instability
      throughout the procedure requiring inotropic support. Haemodynamic values
      obtained through a Swan-Ganz catheter in one patient showed marked changes during
      the procedure, but values returned to normal after the operation. Although these
      patients were haemodynamically unstable there was no problem with hypoxaemia.

PMID- 7524778
TI  - Single-lumen endotracheal intubated anaesthesia for thoracoscopic sympathectomy-
      experience of 719 cases.
AB  - A total of 719 thoracoscopic sympathicotomies were performed at our hospital from
      October, 1989 to December, 1992. We have been practicing single-lumen
      endotracheal intubation for general anaesthesia in all of our cases. We will
      review our experience and discuss our anaesthetic technique and the
      intraoperative complications encountered as well as post-operative pain control.
      General anaesthesia with controlled manual ventilation assisted the surgeon well
      and created clear access for electro-cauterisation of the sympathetic chain.
      Thirty patients were randomly chosen for arterial blood gas analysis. There was
      no evidence of systemic hypoxaemia or clinically significant carbon dioxide
      retention throughout the surgery or afterwards in the recovery room. In our
      experience of 719 cases, single-lumen endotracheal intubated anaesthesia is safe
      and economic for thoracoscopic sympathicotomy.

PMID- 7524781
TI  - Degeneration activity: a transient effect following sympathectomy for
      hyperhidrosis.
AB  - The degeneration activity of effector organs is due to a period of transmitter
      release from degenerating sympathetic post-ganglionic nerve endings. This is the
      theoretical explanation for a period of sweating some days following
      sympathectomy for hyperhidrosis seen in some patients operated on with the
      thoracoscopic technique in Jonkoping, Sweden. The reasons for degeneration
      activity, well documented in animal experiments, are discussed in this paper.

PMID- 7524782
TI  - Intraoperative cardiac arrest: a rare complication of T2,3-sympathicotomy for
      treatment of hyperhidrosis palmaris. Two case reports.
AB  - Endoscopic surgery, including thoracoscopic sympathicotomy for treatment of
      hyperhidrosis, is thought to be safe and entail fewer complications as compared
      with open methods. A total of more than 719 patients with hyperhidrosis have
      undergone thoracoscopic T2,3-sympathicotomy for treatment of hyperhidrosis at
      Tainan Municipal Hospital since October 1, 1989. Most of the complications have
      been minor; however, two of the patients suffered from sudden cardiac arrest at
      the time when the left T2,3-sympathetic nerve trunk was transected by the
      thoracoscopic method. Vigorous cardiopulmonary resuscitation was performed and
      both patients recovered completely without any sequelae. The purpose of this
      paper was to discuss the possible mechanism of cardiac arrest in thoracoscopic
      sympathicotomy, and to emphasise this rare but potentially fatal complication in
      the treatment of hyperhidrosis palmaris.

PMID- 7524783
TI  - The punch and purse-string suture technique.
AB  - Palmar hyperhidrosis can be successfully treated by thoracoscopic sympathicotomy,
      the anterior approach being the most common one. Unfortunately the resulting
      scars are blemishing. Incision on the upper frontside of thorax leave conspicuous
      scars and not uncommonly keloids. Likewise the traditional method used for
      radical excision of naevi leaves large scars in comparison with the size of the
      mark removed. With the increased awareness of malignant melanoma excision of
      birthmarks and naevi is increasingly being demanded. There is also a desire for
      more cosmetically acceptable scars. Is it possible, then, to reduce the size of
      these scars and make them less conspicuous? In two separate studies a new method
      has been designed and tested--the punch and purse-string suture technique by
      which the size of the scars is reduced and of a different shape. In one of the
      studies, the traditional method and the new technique were compared in the same
      patient.

PMID- 7524786
TI  - Endoscopic electrocautery of the upper thoracic sympathetic chain: a safe and
      simple technique for treatment of sympathetically maintained pain.
AB  - Transthoracic endoscopic electrocautery of the upper thoracic ganglia was applied
      to seven patients with sympathetically maintained pain (SMP) in the upper
      extremity, diagnosed by local anaesthetic stellate ganglion blocks. The mean (SD)
      pain intensity of 67 (13) mm as evaluated by means of a visual analogue scale was
      reduced by 79 (27%) postoperatively and this effect persisted after 3 months.
      Long term follow up comprises two patients so far (one year and two years,
      respectively) who have had no recurrence of SMP. No complications occurred. The
      operation was found to be fast, safe and effective and it highlights the
      enigmatic role of the sympathetic nervous system in chronic pain.

PMID- 7524784
TI  - The history of cervicothoracic sympathectomy.
AB  - As early as in 1889 surgery on the cervical sympathetic nervous system was
      performed. During the following decades this operation was tried for a variety of
      diseases. In the early 1920s it was clarified that patients with hyperhidrosis,
      vasospastic conditions, and angina pectoris would benefit from stellectomy. It
      was, however, soon discovered that removal of the upper thoracic ganglia was
      required in order to obtain complete sympathetic denervation of the upper
      extremity. Several open surgical techniques for upper thoracic sympathectomy were
      described. During the 1940s a few pioneers started to excise sympathetic ganglia
      by thoracoscopy which had originally been described as a diagnostic tool by
      Jacobaeus in 1910. The endoscopic approach, amply documented by Kux in 1954, did
      not, however, gain widespread popularity until the 1980s. Like the general
      upsurge of interest in endoscopic surgery, thoracoscopic ablation of the upper
      thoracic sympathetic ganglia is now rapidly being adopted by surgeons.

PMID- 7524787
TI  - Bilateral thoracoscopic lower sympathetic-splanchnicectomy for upper abdominal
      cancer pain.
AB  - Upper abdominal pain secondary to cancer may cause great disability to patients.
      Surgical sympathetic-splanchnicectomy, or coeliac plexus block, has been used to
      relieve intractable upper abdominal cancer pain from stomach, liver, gallbladder
      or pancreas for a long time. There are, however, intrinsic disadvantages when
      performing these procedures. Due to our long experience of therapeutic
      thoracoscopy, we recently performed bilateral thoracoscopic sympathetic
      splanchnicectomy on 14 patients (eight male and six female) for relief of pain
      from primary or metastatic upper abdominal cancers. Most of them were satisfied
      with the immediate pain relief after the operation. In this new era of
      therapeutic endoscopy, endoscopic surgery will gradually take the place of open
      methods in treatment of many diseases. It can be anticipated that thoracoscopic
      lower sympathetic-splanchnicectomy is undoubtedly a good alternative method for
      management of intractable upper abdominal pain.

PMID- 7524785
TI  - Thoracoscopic sympathicotomy for hyperhidrosis--surgical technique, complications
      and side effects.
AB  - Thoracic sympathectomy is a very effective treatment of palmar hyperhidrosis. The
      described endoscopic technique has given good primary results in 99% of patients.
      After another session with this type of "minimal invasive surgery" 100% of the
      hands were satisfactorily dry. The hospital stay is just one post-operative day
      and the sick-leave is about a week. The drawbacks are minimal. Pain is tolerable
      and only eight patients needed a post-operative Bulau-drainage because of
      pneumothorax or bleeding. About 50% of patients experience a compensatory
      increased sweating of the trunk, but this is related to a warm environment and
      regulation of body temperature and seems to decrease with time. This technique
      makes it possible to treat all those suffering from palmar hyperhidrosis which
      can be a substantial, but underestimated handicap. To meet this kind of patient
      after a successful operation is extremely satisfying even for the surgeon. The
      post-operative wet and cold hand has immediately post-operatively become warm and
      dry.

PMID- 7524788
TI  - Thoracoscopic sympathicotomy for arterial insufficiency.
AB  - Arterial insufficiency of the hands due to vascular spasm-morbus Raynaud is an
      extremely unpleasant condition. Elicited by cold temperatures, the disease can
      make it impossible for the patient to go out in cold environments. The condition
      seldom leads to skin necrosis, which is the case in arterial insufficiency caused
      by vascular occlusion. In both cases arterial insufficiency may be diminished by
      thoracic sympathectomy. Our test series of operations included 14 patients with
      m. Raynaud or vascular occlusion. All experienced improvement, with warm, dry
      hands and satisfactory healing after thoracoscopic sympathicotomy. However, after
      six months, the original symptoms recurred in all the patients with m. Raynaud,
      while the improvement continued in the patients with vascular occlusion during
      the two to four year period of observation.

PMID- 7524789
TI  - Cardiac effects of endoscopic electrocautery of the upper thoracic sympathetic
      chain.
AB  - Bilateral endoscopic electrocautery of the upper thoracic sympathetic ganglia (T2
      4) was performed, mainly for palmar hyperhidrosis, on 535 patients. The aim of
      this study was to evaluate the effects of this procedure on cardiac and physical
      performance. A subgroup of 18 patients underwent cycle ergometer test with ECG
      recordings before and three months after surgery. After the operation, a
      significantly reduced heart rate at rest (12%) as well as during exercise and
      during recovery after exercise was found. The systolic blood pressure was reduced
      only at rest (7%) and the diastolic blood pressure was not significantly altered.
      Maximal workload was not affected by the operation and only a few patients had
      noticed their reduced heart rate. Three patients with angina pectoris and three
      with incapacitating tachycardia related to mental stress were operated on with
      excellent results. Thoracoscopic sympathicotomy is a safe, fast, cheap and
      efficient method for cardiac sympathetic denervation. This procedure might
      constitute an alternative to long-term thoracic epidural anaesthesia and
      implantation of thoracic electric stimulation devices in patients not suited for
      aortocoronary by-pass. Patients who require cardiac beta-receptor blockers and
      suffer from side effects of these drugs might also benefit from surgical cardiac
      sympathetic denervation.

PMID- 7524790
TI  - Surgical treatment of palmar hyperhidrosis before thoracoscopy: experience with
      475 patients.
AB  - Between the years 1968-1992, 475 patients underwent simultaneous bilateral upper
      dorsal sympathectomy by the supraclavicular approach for severe palmar
      hyperhidrosis. For the purpose of comparing outcomes of the open surgical method
      with the increasingly used thoracoscopic procedure, we reviewed the clinical data
      of our patients. The incidence of severe palmar hyperhidrosis in the young
      population in Israel is 1-2/1,000. Surgical excision of the T2 and T3 ganglia was
      effective in drying the hands of all patients, who had frozen section
      confirmation of removal of a ganglion. At follow-up, hyperhidrosis recurred in
      5.3% of limbs. Mild transient Horner's syndrome occurred in 12% of procedures,
      but only in 5 patients was it permanent. The main drawback of the open surgical
      approach lies in the postoperative complications. The effectiveness of the
      thoracoscopic approach will be judged by immediate and late results, and by the
      expected reduction in postoperative morbidity.

PMID- 7524792
TI  - A multicentre in vitro evaluation of piperacillin/tazobactam in Germany.
AB  - In a multicentre study in Germany 10584 fresh clinical aerobic isolates were
      tested for susceptibility to piperacillin (30 micrograms or 100 micrograms discs)
      and piperacillin/tazobactam (30 micrograms/10 micrograms or 100 micrograms/10
      micrograms discs). Preliminary breakpoints for piperacillin/tazobactam according
      to the German standard methods (Deutsches Institute fur Normung) were: Resistant:
      inhibition zone < or = 14 mm; MIC > or = 64 mg/l. Susceptible: inhibition zone >
      or = 22 mm; MIC D or = 4 mg/l. For comparison, the National Committee for
      Clinical Laboratory Standards (USA) breakpoints for enterobacteria (100/10
      micrograms/disc) are: Resistant: inhibition zone < or = 17 mm; MIC > or = 128/4
      mg/l. Susceptible: inhibition zone > or = 21 mm; MIC < or = 6/4 mg/l. Using the
      DIN criteria, 73.2% of Enterobacteriaceae tested were susceptible to piperacillin
      and 91.2% to piperacillin/tazobactam. Of Staphylococcus aureus strains tested
      (including methicillin resistant Staphylococcus aureus, MRSA), 20.8% were
      susceptible to piperacillin and 78.7% to piperacillin/tazobactam. The MIC of
      piperacillin/tazobactam for most staphylococci and Enterobacteriaceae that had
      been classified on the first test as having intermediate susceptibility or
      resistance to piperacillin/tazobactam by DIN criteria were re-evaluated to solve
      methodological problems and inconsistencies among the participating laboratories.
      This second study resulted in a reduction of the zone diameter for susceptibility
      of staphylococci to > 14 mm and found that an additional 55.7% of
      resistant/intermediate Enterobacteriaceae and 91.0% of resistant/intermediate S
      aureus were susceptible to piperacillin/tazobactam, giving totals for
      susceptibility of 96.1% for Enterobacteriaceae and 98.1% for S aureus.

PMID- 7524791
TI  - Enterococcis: pathogens of the 90s.
AB  - The genus Enterococcus consists of at least 12 species, two of which account for
      over 95% of the clinically important strains, E faecalis (85%-90%) and E faecium
      (5%-10%). Despite their ubiquity and frequent isolation, they have not been
      thought to cause serious disease because they lack common virulence factors. Now,
      however, enterococci are regarded as true pathogens and are the second leading
      cause of nosocomial infections. This change results from their increasing
      antimicrobial resistance and the extensive use of antimicrobial drugs (for
      example-cephalosporins) that are not active against them. Serious infections
      should usually be treated with a beta-lactam and an aminoglycoside, but
      glycopeptides have been increasingly used during the last decade. Two novel
      resistance patterns of particular concern recently are high level aminoglycoside
      resistance (HLAR) and vancomycin resistance. The prevalence of HLAR is between
      15% and 55%, and glycopeptide resistance has become widespread in various
      geographical areas. This poses a serious problem, as such resistance may spread
      to other Gram-positive organisms and is often associated with resistance to other
      antimicrobial drugs. This may theoretically result in groups of organisms for
      which there will be no effective antimicrobial treatment.

PMID- 7524794
TI  - Pharmacokinetics and tissue penetration of piperacillin/tazobactam with
      particular reference to its potential in abdominal and soft tissue infections.
AB  - Piperacillin/tazobactam is a new drug consisting of a highly active penicillin
      and a beta-lactamase inhibitor. Pharmacokinetic variables of both components
      after they have been given together have been studied in healthy volunteers and
      in patients. Drug analysis in all studies was done by specific high pressure
      liquid chromatography (HPLC). In this review we summarise the pharmacokinetic
      properties of piperacillin/tazobactam. Most importantly, data on the piperacillin
      show that its behaviour is not changed when it is given with tazobactam. The
      pharmacokinetics of tazobactam are typical of beta-lactams, including the tissue
      penetration. It is distributed mainly into the extra-cellular space. Tissue
      concentrations of piperacillin/tazobactam and the concentrations of the two
      agents and their time course in plasma and tissue indicate that this combination
      is well formulated and truly synergistic pharmacokinetically. Clinical trials
      will show how these characteristics influence treatment outcomes.

PMID- 7524795
TI  - Efficacy of piperacillin/tazobactam in the treatment of experimental intra
      abdominal infections.
AB  - A reproducible animal model of intra-abdominal infection was devised to simulate
      intra-abdominal sepsis in humans and emulate clinical trials. Preoperatively,
      rats were fed lean ground beef for two weeks to change their intestinal flora to
      one similar to that of humans. A 1 cm segment of ileum was isolated on its
      vascular pedicle. The intestine was then divided at each end of the segment and
      continuity re-established by end-to-end anastomosis. The isolated segment was
      returned to the abdominal cavity. This model was used to compare
      piperacillin/tazobactam with imipenem and with clindamycin plus gentamicin in
      treating the resulting infections. Eighty per cent of untreated animals died
      within three days. Treated animals had significantly reduced mortality and
      increased cure rates. One treated animal (in the clindamycin-gentamicin group)
      died. These results support the findings of the efficacy of
      piperacillin/tazobactam in treating intraabdominal infections in human clinical
      trials.

PMID- 7524793
TI  - Anaerobes in polymicrobial surgical infections: incidence, pathogenicity, and
      antimicrobial resistance.
AB  - Many types of anaerobic bacteria have been isolated from clinical infections.
      Although most of these infections are polymicrobial and involve facultative Gram
      negative bacilli, some are strictly anaerobic. For most of them, surgical
      intervention such as drainage of an abscess and debridement of devitalised tissue
      is the primary treatment and re-establishes good blood flow to the affected area.
      Appropriate antimicrobial treatment is also important to kill both residual
      organisms and those that may have spread from the site of primary infection.
      Several groups of anaerobes (for example, Bacteroides fragilis group, Prevotella,
      Porphyromonas, and Fusobacterium) have developed mechanisms of resistance to beta
      lactam agents, the most common of which is production of beta-lactamases. A
      recent approach to neutralising these enzymes has been to combine the beta-lactam
      agent with an irreversible beta-lactamase inhibitor. Because of their potency
      against both aerobes and anaerobes, these combinations may replace traditional
      combination treatment (gentamicin/clindamycin) for polymicrobial infections.
      Piperacillin/tazobactam was the beta-lactam/beta-lactamase combination that was
      most active against the B fragilis group in the present study.

PMID- 7524796
TI  - Efficacy and safety of piperacillin/tazobactam in skin and soft tissue
      infections.
AB  - Piperacillin/tazobactam has excellent in vitro activity against the most
      pathogens involved in skin infections. Two large multicentre studies recently
      evaluated the efficacy and safety of piperacillin/tazobactam in the treatment of
      skin and soft tissue infections in patients in hospital. The efficacy and safety
      of piperacillin/tazobactam (4 g/500 mg every 8 hours) have been assessed in an
      open study in Europe. Among 120 evaluable patients, 93% were clinically cured or
      improved. Only six patients were withdrawn from the study because of side
      effects. In another trial, piperacillin/tazobactam were compared with
      ticarcillin/clavulanate in a double-blinded prospective study in the United
      States. Of evaluable patients, 67 received piperacillin/tazobactam (3 g/375 mg
      every 6 hours) and 44 received ticarcillin/clavulanate (3 g/100 mg every 6
      hours). At assessment, 76% of patients given piperacillin/tazobactam and 77% of
      patients given ticarcillin/clavulanate had responded favourably. The lower
      success rate in this trial may be attributed to more stringent inclusion criteria
      that resulted in the incorporation of a higher proportion of patients with more
      severe conditions including diabetic/ischaemic foot infections. The incidence of
      adverse reactions was similar in both groups. Piperacillin/tazobactam seems to be
      both effective and safe in the treatment of skin and soft tissue infections in
      patients confined to hospital.

PMID- 7524797
TI  - Efficacy and safety of piperacillin/tazobactam in intra-abdominal infections.
AB  - Intra-abdominal infections are a serious problem for surgeons. Treatment consists
      of a combination of operation, antimicrobial treatment, and supportive measures.
      beta-Lactam antibiotics have a major role in the treatment of peritonitis, and in
      combination with beta-lactamase inhibitors, the penicillins have an even larger
      part to play than previously. A multicentre prospective trial to evaluate the
      efficacy and safety of piperacillin/tazobactam in the treatment of serious intra
      abdominal infections was conducted in Europe. One hundred and six evaluable
      patients with documented intra-abdominal infections were treated with
      piperacillin 4 g/tazobactam 500 mg every eight hours. The most common diagnoses
      were peritonitis, intra-abdominal abscess, and complicated diverticulitis. A 90%
      favourable clinical response rate (cured/improved) was found during the first two
      weeks of treatment. Piperacillin/tazobactam was extremely active against the Gram
      negative aerobic, Gram-positive aerobic, and anaerobic bacteria isolated in this
      trial. Overall, the drug was well tolerated and the side effects were minimal.

PMID- 7524798
TI  - Results of the North American trial of piperacillin/tazobactam compared with
      clindamycin and gentamicin in the treatment of severe intra-abdominal infections.
      Investigators of the Piperacillin/Tazobactam Intra-abdominal Infection Study
      Group.
AB  - A total of 192 men and 139 women aged 15 to 89 years with diagnosed intra
      abdominal infection were randomised in a 2:1 ratio to treatment with either
      intravenous piperacillin/tazobactam (3 g/375 mg every six hours) or clindamycin
      (600 mg every six hours) plus gentamicin (2.5 mg to 5.0 mg/kg every eight to 12
      hours) in a multicentre trial. Of 147 evaluable patients with microbiologically
      confirmed infections, 104 were treated with piperacillin/tazobactam and 43 with
      clindamycin plus gentamicin. The diagnoses of perforated appendicitis (n = 79),
      other peritonitis (n = 32), cholecystitis/cholangitis (n = 18), intraabdominal
      abscess (n = 14), and diverticulitis (n = 3), were distributed proportionately
      between the two therapeutic groups. Ninety one of 104 patients (88%) in the
      piperacillin/tazobactam group and 33 of 43 patients (77%) in the clindamycin plus
      gentamicin group were considered cured or improved (p = 0.13). In the
      piperacillin/tazobactam group, 80 of 88 (91%) Bacteroides fragilis group
      organisms and 68 of 74 (92%) E coli isolates were eradicated; in the clindamycin
      plus gentamicin group, 21 of 25 (84%) Bacteroides fragilis group isolates and 23
      of 30 (76%) E coli isolates were eradicated. Eleven evaluable patients in the
      piperacillin/tazobactam group had beta-lactamase-producing organisms that were
      resistant to piperacillin but susceptible to piperacillin/tazobactam; in 10 of
      these patients (91%) bacteria were eradicated. We conclude that
      piperacillin/tazobactam is an effective antimicrobial drug for monotherapy of
      intra-abdominal infections, with efficacy similar to or better than standard
      aminoglycoside/anti-anaerobe combinations.

PMID- 7524799
TI  - Assessing cost effectiveness of antimicrobial treatment: monotherapy compared
      with combination therapy.
AB  - The obvious costs of antibiotic treatment include drugs, equipment with which to
      give them, and assays. Less obvious, but more important, are the costs of quality
      control to ensure safe and effective treatment. The more complex the regimen, the
      more expensive the quality control. None the less, there is considerable
      variation in both assay price and number of assays/patient. Our data show that
      the drug costs of a regimen such as ampicillin plus gentamicin plus metronidazole
      are outweighed by the costs of quality assurance to prevent drug toxicity and
      charges of malpractice. Trials show that monotherapy with various beta-lactams is
      more cost effective than aminoglycoside combinations for surgical infections.
      Compounds such as piperacillin/tazobactam, a new beta-lactam/beta-lactamase
      inhibitor combination that is classed as monotherapy, have the potential to solve
      many of these economic problems. Several completed and continuing clinical
      studies are showing that monotherapy is as effective as combination treatment.
      Cost studies in the future are likely to confirm the economic advantages of
      monotherapy.

PMID- 7524800
TI  - Emerging trends in antimicrobial resistance in surgical infections. A review.
AB  - During the past decade there have been major changes in the susceptibility of
      bacteria that cause surgical infections. Resistance to common bacteria is
      worldwide, both in developed and developing countries. Almost all species of
      bacteria can develop resistance to antimicrobial agents, and resistance can
      readily be transferred among bacteria by transmissible elements called plasmids.
      One of the most important forms of resistance has been the inactivation of
      antibiotics, particularly penicillins and cephalosporins. The organisms involved
      in surgical infections include staphylococci, streptococci, enterococci, members
      of the Enterobacteriaceae, Pseudomonads, and anaerobes. Today virtually all
      Staphylococcus aureus are resistant to penicillins. Coagulase-negative
      staphylococci are also increasingly important causes of infection, particularly
      in cardiovascular surgery, where they may cause serious postoperative
      complications. Like S aureus, coagulase-negative staphylococci, primarily S
      epidermidis, also produce beta-lactamases and can be resistant to all beta-lactam
      antibiotics because of altered penicillin-binding proteins. New beta-lactamases,
      which destroy extended-spectrum beta-lactam antibiotics, have developed in
      Enterobacteriaceae, and all Pseudomonas spp. possess beta-lactamases. Various
      techniques have been used to overcome resistance, one of which is the development
      of beta-lactamase inhibitors. Currently there are three compounds that are
      effective inhibitors of many beta-lactamases: clavulanate, sulbactam, and
      tazobactam. The problem of resistance in surgical infections will not disappear.
      Increasingly complex operations will be done on more debilitated patients. The
      development of beta-lactamase inhibitors combined with highly active beta-lactam
      antibiotics has provided a way of overcoming this form of resistance.

PMID- 7524801
TI  - Sister chromatid exchange studies for monitoring DNA damage in lymphocytes of
      malignant lymphoma patients under cytostatic therapy.
AB  - Sister chromatid exchange (SCE) frequencies were studied in lymphocytes from 45
      patients with malignant lymphoma. Fifteen patients were untreated when studied.
      The mean SCE frequency for these patients was 8.70 +/- 0.99 per mitosis. The mean
      score for 35 controls was 4.37 +/- 1.19. SCE mean scores were significantly
      higher in the untreated patients than in the controls (p < 0.001). Nine patients
      were treated with radiotherapy alone. The mean SCE frequency (6.80 +/- 0.87) they
      demonstrated was significantly lower (p < 0.01) than that found in untreated
      patients. Twelve patients received cyclophosphamide 1 month before the study was
      started. They demonstrated a mean SCE frequency (12.00 +/- 1.31) significantly
      higher (p < 0.05) than that found in patients who had received regimens that did
      not contain cyclophosphamide (9.72 +/- 1.32). From these findings we suggest that
      untreated patients with malignant lymphoma have elevated SCE frequencies, which
      may be further increased by chemotherapeutic agents.

PMID- 7524802
TI  - Long-term follow-up study of adenomatous hyperplasia in liver cirrhosis.
AB  - The purpose of this study was to investigate the natural history of adenomatous
      hyperplasia (AH) in liver cirrhosis, which is suspected of being a precancerous
      condition of hepatocellular carcinoma (HCC). Sixteen patients with 19
      histologically proven AH nodules were followed-up over time with ultrasonographic
      (US) examinations performed every 3-4 months. The biopsy was repeated whenever
      the volume of the lesion increased, its US pattern changed, or there was a change
      in the alpha-fetoprotein values. Thirteen out of 19 AH (68.4%) evolved toward HCC
      after 8-31 months (mean 14.2 months). Malignant transformation was proved in 7/18
      AH within 1 year of its initial detection, in 12/15 AH within 2 years, and in
      13/14 AH within 4 years. Six AH remained unchanged in size and US pattern for 9
      70 months (mean 29.5 months). Long term follow-up of AH confirms that this lesion
      is a precursor of HCC.

PMID- 7524803
TI  - A case of hepatocellular carcinoma that resisted identification.
AB  - The case of a 70-year-old man with clinically-compensated alcoholic liver
      cirrhosis is illustrated. His serum alpha-fetoprotein level was on the increase
      but Ultrasonography and Magnetic Resonance detected no focal lesion of the liver.
      Five months after Ultrasonography, Computed Tomography and Magnetic Resonance
      were performed because the patient's alpha-fetoprotein level indicated
      hepatocellular carcinoma, but none of these tests succeeded in locating the
      neoplasm. Digital subtraction angiography was performed and only then was a small
      hepatocellular carcinoma revealed under the diaphragm. The patient underwent
      transcatheter arterial chemo-embolization with the result that the alpha
      fetoprotein level dropped immediately and is still normal after 15 months. The
      case described is a model of what the ideal function of a marker of neoplasia
      should be, namely early detection, and subsequent precise confirmation of the
      continuing efficacy of the treatment adopted.

PMID- 7524804
TI  - [Screening for post-transfusion hepatitis C-importance of enrollment and recall
      of blood transfusion recipients].
AB  - OBJECTIVE: To detect chronic hepatitis C virus infection in recipients of blood
      products. DESIGN: Retrospective analysis by recall and enrollment of recipients.
      PATIENTS AND METHODS: Two-hundred twenty-six patients who received blood products
      in Tokushima for open heart surgery from January 1993 to December 1992 were
      examined for HCV antibodies by second-generation assay and surrogate markers.
      RESULTS: Twenty two (14%) of the 161 patients who received blood products before
      Nov 1989 had detectable HCV antibodies, but none of the 65 recipients receiving
      blood after 1990, the year the blood bank began to screen for HCV-antibody. Of 22
      seropositive patients, HCV RNA (ribonucleic acid) was recognized in 10 (45%) by
      HCV PCR (polymerase chain reaction) method, indicating persistent HCV infection.
      Moreover, abnormal alanine aminotransferase (ALT), more than 25 IU/l, during the
      chronic phase of HCV infection was recognized in 9 of 10 patients with detectable
      HCV RNA, but none in patients with undetectable HCV RNA. In the 15 patients in
      whom liver biopsy was performed, 10 had abnormal histology; 4 chronic active
      hepatitis, 6 chronic persistent hepatitis, and 5 had normal histology.
      CONCLUSION: It is Important to recall and screen for chronic hepatitis C In blood
      product recipients, since persistent and active HCV infection is often
      assymptomatic, yet treatable.

PMID- 7524806
TI  - Rearrangements of doubly charged acylium ions from lysyl and ornithyl peptides.
AB  - The study of large-scale rearrangements of [b']2+ ions produced by electrospray
      ionization of Substance P (Tang et al., Anal. Chem. Vol. 65, p. 2824 (1993)) has
      been extended to 18 other peptides containing either a lysine or ornithine
      residue remote from the C-terminus. Evidence for wholesale transfer of one or
      more residues, from the C-terminus of the [b']2+ precursor to the omega-amino
      group of the Lys (or Orn) residue, was observed for 12 of the 18 peptides
      studied. Unfortunately, no rigorous predictive rules, relating features of the
      peptide sequence to the propensity to undergo such rearrangements, could be
      discerned although a significant correlation with presence of a proline residue
      close to the lysine or ornithine on the C-terminal side was apparent. The
      resulting mass-shifts can complicate derivation of peptide sequences from
      fragment-ion spectra of [M + 2H]2+ peptide ions, for example, since the cyclized
      [b']2+ ions responsible for the rearrangements are readily formed as intermediate
      species in the fragmentation mechanisms.

PMID- 7524805
TI  - On-line buffer removal and fraction selection in gradient capillary high
      performance liquid chromatography prior to electrospray mass spectrometry of
      peptides and proteins.
AB  - The technique for on-line removal of buffers and for fraction selection to
      eliminate source clogging and suppression of electrospray ionization by unwanted
      constituents consisted of: (i) selecting the initial mobile phase composition to
      retain analytes on top of a capillary high-performance liquid chromatography
      (HPLC) column; (ii) washing the buffer isocratically to waste, using a two-way
      micro dump valve; (iii) starting the gradient and switching the dump valve to
      introduce analytes into the source. Peptide and protein mixtures were prepared in
      0.05-0.5 M phosphate and 0.55 mM tris-based buffers, and water. After buffer
      removal, chromatograms and electrospray spectra were indistinguishable from those
      of aqueous controls, down to 1 pmol (acidic fibroblast growth factor) consumed,
      and up to 78 kDa (bovine transferrin) molecular weight. Aided by the dump valve,
      100 fmol of angiotensin could be fractionated and identified on the slope of a 10
      x 10(6) fmol of leucine enkephalin HPLC peak. On-line buffer removal and fraction
      selection eliminate the need for additional preparation steps than can lead to
      excessive sample losses.

PMID- 7524807
TI  - Detection limits for matrix-assisted laser desorption of polypeptides with an
      external ion source Fourier-transform mass spectrometer.
AB  - Sensitivity in the low-femtomole range with mass resolution greater than 20,000
      is demonstrated for several polypeptides analyzed by a mass spectrometer that
      pairs matrix-assisted laser desorption/ionization (MALDI) and Fourier-transform
      mass spectrometry (FTMS). The compounds investigated were substance P, renin
      substrate, melittin, the B-chain of bovine insulin, and bovine insulin. Standard
      solutions of the polypeptides were prepared with 30% acetonitrile+water, and
      micropipettes were used to transfer small amounts (1-20 fmol) to a sample probe.
      The samples were embedded in a large excess of matrix material (2,5
      dihydroxybenzoic acid) and ionized by a pulse from an excimer laser. The FTMS
      instrument used for these experiments has the MALDI source in a separate chamber
      outside the magnetic field. Ions are extracted from the source and transported by
      an RF-only quadrupole ion guide to an FTMS analyzer cell mounted in the
      homogeneous region of a 6.5 T superconducting magnet. The high sensitivity of
      MALDI-FTMS is due, in part, to the high transfer efficiency of the ion guide,
      even for ions with a wide range of kinetic energies. The ion guide is easy to use
      because there are only two adjustments (RF amplitude and DC offset voltage), and
      unlike electrostatic ion transport means, alignment of it with the axis of the
      magnetic field is not critical. The mass resolution and sensitivity of MALDI-FTMS
      is compared with that of MALDI done with time-of-flight, magnetic sector, and
      quadrupole ion-trap mass spectrometers.

PMID- 7524808
TI  - Immunochemical identification of abnormal constituents in the dermis of
      pseudoxanthoma elasticum patients.
AB  - Pseudoxanthoma elasticum (PXE) is a connective tissue inherited disease
      characterized by dermal alterations and mineralization of the elastin fibres. To
      investigate its pathogenesis, which is still unknown, antibodies against the
      principal connective tissue components were assayed on ultrathin sections of
      dermis from 7 PXE subjects and 5 age matched controls. Both control and PXE
      elastin fibres were positive for heparan, dermatan and chondroitin 0-sulphates,
      decorin and biglycan. In PXE, elastin fibres were also highly positive for
      chondroitin 6-sulphate, vitronectin, fibronectin and serum amyloid antigen.
      Vitronectin and fibronectin were mostly concentrated in the areas of dense
      mineralization within the elastin fibres. The abnormal microfilament aggregates,
      often seen in PXE dermis, were positive for all the above mentioned molecular
      species as well as for collagen types I and III and fibrillin; on the contrary,
      they were always negative for elastin. The results suggest that PXE is a complex
      disorder, in which the whole extracellular matrix is deeply disturbed. Therefore,
      without excluding an elastin gene defect, the data seem rather to suggest that
      PXE is a disorder of the mechanisms controlling the production of matrix
      constituents and that elastin mineralization is caused by molecules abnormally
      produced and entrapped within the fibre during elastin fibrogenesis.

PMID- 7524809
TI  - Enzymatic activity and morphological differentiation in de novo innervated human
      muscle cultures.
AB  - In the present series of experiments, we studied the effects of developmental
      neural control on morphological differentiation and on the activity of muscle
      specific (creatine kinase, CK; phosphoglycerate mutase, PGAM; phosphorylase, PPL;
      and phosphofructokinase, PFK) and non-specific (acid maltase, AM; glucose-6
      phosphate dehydrogenase, G6PD), human muscle enzymes in de novo innervated muscle
      cultures. Following innervation of muscle cultures, we noted an increase in the
      activity of CK, PPL, PFK and AM along with a reduction in G6PD activity. There
      was also a change of the CK isoenzymes present in the myotubes, i.e. BB and MB
      are the major isoenzymes in non innervated cultures, but MM becomes predominant
      following innervation. In the case of PGAM, the only isoenzyme present in the non
      innervated cultures was BB while the MM isoform appeared only after a prolonged
      innervation period in most cases--with the exception of AM--these changes in
      enzyme activity and in the type of isoenzymes present, demonstrate that
      innervated cultures are more similar to mature muscle. This maturation of
      enzymatic activity correlates well with the morphological maturation of the
      myotubes observed following innervation. Such innervated cultures therefore
      represent a better model with which to study the morphological and biochemical
      abnormalities associated with neuromuscular diseases.

PMID- 7524811
TI  - Modification induced by ACTH in hemocyte cytoskeleton of the freshwater snail
      Viviparus ater (Gastropoda, Prosobranchia).
AB  - Adrenocorticotropin hormone (ACTH) is able to induce motile events in the
      phagocytic hemocytes of Viviparus ater by modifying the cytoskeletal components.
      The cell shape changes into a polarized morphology. The microfilament bundles,
      which, in control cells display a radial distribution from the nucleus to the
      cell periphery, are arranged under the plasma membrane. Moreover, on the
      protruded lamellipod, actin is accumulated in small, round structures. The
      microtubule component increases and seems to contribute to the maintenance of
      cell polarity. Hemocyte adhesive properties are also modified, and different
      localization patterns of extracellular fibronectin are observed. Cellular
      responses induced by the ACTH signal may be mediated by cyclic 3',5'-AMP (cAMP).

PMID- 7524810
TI  - Histochemical and biochemical studies of the kinetics of non-specific acid
      phosphatase in rat kidney.
AB  - Kinetic characteristics of non-specific acid phosphatase (orthophosphoric
      monoester phosphohydrolase, E.C.3.1.3.2.) from rat kidney were determined
      fluorometrically using 4-methylumbelliferyl phosphate as the substrate. Kinetic
      characteristics measured by similar methods both histochemically in cryostat
      sections and biochemically in tissue extracts were compared. Histochemical and
      biochemical methods gave essentially similar results in respect of Michaelis
      Menten constants (Km), pH optima, effect of fluoride inhibition and the effect of
      changes in incubation temperatures in the range 10 degrees C to 37 degrees C.
      This confirms the validity of both methods, and also gives greater confidence
      that the enzyme in vitro closely approximates the properties of the enzyme as it
      functions in vivo.

PMID- 7524812
TI  - PCNA/cyclin expression and BrdU uptake define proliferating myosatellite cells
      during hyperplastic muscle growth of fish (Cyprinus carpio L.).
AB  - The possibility of detecting in situ proliferating myosatellite cells during
      postlarval muscle growth in the carp (Cyprinus carpio, L.) by means of BrdU and
      PCNA (Cyclin) immunohistochemistry has been evaluated on paraffin embedded
      sections. Nine subadult stages were defined according to the body length and
      weight. The fish were injected intraperitoneally with BrdU and fixed one hour
      later. Adjacent cross sections mounted on glass slides were incubated with
      monoclonal antiBrdU (1:100) and antiPCNA (1:200) antibody. The proliferative
      rate, defined as the percentage of labelled cells for each stage, was correlated
      to the corresponding percentage of small fibers (area less than 200 microns 2)
      determined by morphometric analysis. Desmin expression, immunocytochemically
      detected, was aimed at discriminating between the postmitotic and stem
      myosatellite cells. A low myosatellite cell proliferative activity (2-7%)
      throughout the carp growth period considered was demonstrated. Quantitative
      analysis provided evidence that during growth stages in which small fibers are
      numerous, the myosatellite cell proliferative activity is low and it increases
      when the small fibers number decreases. It is suggested that an age dependence of
      myosatellite cell proliferative rate controls the recruitment of new fibers in
      the carp.

PMID- 7524813
TI  - Cytometric ploidy and proliferative activity in colorectal carcinoma.
AB  - Thirty cases of colorectal carcinoma have been evaluated for proliferative
      activity with the monoclonal antibody Ki 67 and with flow cytometry for ploidy,
      DNA index and the S-phase fraction. In the series, 30% of tumours were strictly
      aneuploid, 23.8% tetraploid and 45% diploid: "non diploid" cases accounted for
      53.8%. The mean comprehensive values of DNA index, percent S-phase and Ki 67
      positive fraction were 1.4%, 11.5% and 50%, respectively. The parameters
      considered showed no statistically significant correlation with each other or
      with the common histo-pathologic parameters, such as grading and staging. The
      prevalent prognostic importance of ploidy compared to DNA index is emphasized,
      and particular attention is paid to diploid cases with a high growth fraction (S
      phase fraction), which could make up an "at risk" category. Therefore, we
      attempted to identify subsets, within groups of the same histologic stage, with a
      different evolutive significance in relation to DNA content, percentage of
      positivity to Ki 67, S-phase fraction and ploidy. With such a multi-parametric
      approach, particular groups of patients at risk could be defined, which are
      perhaps more sensitive to specific support therapies.

PMID- 7524814
TI  - AgNORs in ductal breast cancer: correlation with ploidy and S-phase fraction by
      DNA flow cytometry.
AB  - Silver-binding nucleolar organizer regions (AgNORs) have been counted in sections
      of routinely processed paraffin embedded material. The AgNOR score has been
      correlated with proliferative activity of various neoplasms. An increase in the
      AgNOR score can be related to cellular growth fractions or DNA-ploidy. We have
      examined 301 invasive ductal breast carcinomas by this method. The AgNOR counts
      were also compared with DNA Ploidy and the S-phase fraction flow cytometry. A
      positive correlation has been found between the AgNOR score and the S-Phase
      fraction. These data show cell proliferation. We conclude that AgNOR counting may
      provide information on breast carcinoma in addition to that obtained from flow
      cytometric analysis.

PMID- 7524815
TI  - Functional aspects of the longitudinal differentiation of chromosomes.
AB  - The discovery of chromosome banding techniques over 20 years ago has revealed
      extensive longitudinal differentiation of chromosomes. This longitudinal
      differentiation can be classified into four types: heterochromatin, euchromatic
      bands, nucleolar organisers (NORs) and kinetochores. The telomeres, at the ends
      of chromosomes, cannot be detected by banding methods, but are clearly shown by
      in situ hybridisation. The functions of nucleolar organisers, kinetochores, and
      telomeres are reasonably well known, but the reasons for the differentiation of
      the greater part of the chromatin into heterochromatin and euchromatic segments
      remains uncertain. The function of heterochromatin may be sought in its
      centrometric location, where part of it is associated with the kinetochores, and
      another part appears to hold the sister chromatids together until anaphase. It
      appears that highly conserved nucleotide sequences are not required for these
      functions, but highly repeated sequences may be necessary. Nevertheless, these
      functions cannot explain the whole of heterochromatin. G-banding and other
      methods for euchromatic banding have shown that the euchromatic parts of
      chromosomes are divided into two major compartments, one gene-rich and the other
      gene-poor, which also differ in many other properties. The reason for this, which
      seems to be a fundamental property of chromosome organisation in eukaryotes, is
      totally obscure. Nevertheless, the observations that the greatest concentrations
      of genes tend to be found near the ends of chromosomes, and that the telomeres
      are often located at the nuclear envelope, suggest that a mechanism may have
      evolved to ensure that active genes are close to the cytoplasm.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7524816
TI  - Pleural effusions: pathophysiology and management.
AB  - OBJECTIVE: To review the pathophysiology and management of pleural effusions,
      including available agents for pleural sclerosis. DATA SOURCES: A MEDLINE search
      (1966 to present) was performed that included clinical studies in the English
      language involving the pathophysiology and management of pleural effusions;
      references used in those articles were screened for additional published
      information. STUDY SELECTION: All clinical trials were considered for potential
      inclusion in the review. DATA SYNTHESIS: Pleural effusion is an accumulation of
      fluid in the pleural space that results when homeostatic forces that control the
      flow into and out of the area are disrupted. The management of transudative
      pleural effusions is primarily directed at treatment of the underlying disease.
      There are several treatment options for pleural effusions, including chemical
      pleurodesis. Many of the trials that examine the use of talc, bleomycin, and
      doxycycline have poorly described study designs and end points, with inconsistent
      evaluation of patients. Each agent is considered to be generally effective and
      safe, with fever and pain as the most frequently reported adverse effects. The
      use of talc requires sterilization, and many clinicians use general anesthesia
      with instillation, which increases the risk associated with the procedure.
      Bleomycin is generally safe; however, it should not be used in doses exceeding 40
      mg/m2. Only uncontrolled trials support the use of doxycycline; however, it
      provides an effective, safe, and relatively inexpensive alternative. CONCLUSIONS:
      Pleural effusions are defined as an accumulation of fluid in the pleural space.
      Treatment is generally palliative. Intrapleural administration of talc,
      bleomycin, and doxycycline are effective sclerosing agents for treatment of
      recurrent, symptomatic pleural effusions. Although the most cost-effective agent
      has not been determined, doxycycline is an inexpensive alternative to bleomycin,
      and may have fewer adverse effects than talc.

PMID- 7524817
TI  - Alternatives to intravenous tetracycline hydrochloride for malignant pleural
      effusions.

PMID- 7524818
TI  - Comment: N,N-dimethylglycine and L-carnitine as performance enhancers in
      athletes.

PMID- 7524819
TI  - Effective production of glycosyl-steviosides by alpha-1,6 transglucosylation of
      dextrin dextranase.
AB  - Dextrin dextranase (EC 2.4.1.2; DDase), which is produced by Acetobacter
      capsulatus ATCC 11894, acted on a mixture of stevioside and starch hydrolysate
      with isoamylase, so that the enzyme was found to convert stevioside to
      predominantly mono-glucosyl-stevioside (SG1) and di-glucosyl-stevioside (SG2),
      and little of the stevioside initially added remained. SG1 was separated into two
      compounds (SG1a and SG1b) by reversed-phase high-pressure liquid chromatography.
      The structures of SG1a, SG1b, and SG2 were analyzed and concluded to be 13-O-(6
      alpha-glucosyl-2-beta-glucosyl-beta-glucosyl)-19-O-beta-glucosyl -steviol, 13-O
      [(6-alpha-glucosyl)(2-beta-glucosyl)-beta-glucosyl]-19-O- glucosyl-steviol, and
      13-O-[(6-alpha-glucosyl)(6-alpha-glucosyl-2-beta- glucosyl)-beta-glucosyl]-19-O
      beta-glucosyl-steviol, respectively. During the reaction for production of
      glycosyl-steviosides, DDase catalyzes transglucosylations from glucosyl donor
      compounds to stevioside to be SG1a and SG1b, and to SG1b to be SG2 rapidly
      forming alpha-1,6 glucosidic linkages. However transglucosylation to SG1a to be
      SG2 rarely occurred, and the conversions among stevioside and these glycosyl
      steviosides were catalyzed by the action of DDase to transfer alpha-1,6 linked
      glucosyl residues, forming alpha-1,6 linkages.

PMID- 7524820
TI  - Congress of the American Society of Urology (ASU), San Antonio (Texas), May 15
      20, 1993.

PMID- 7524821
TI  - Insulin-like growth factor binding proteins and their regulation.

PMID- 7524822
TI  - Effects of insulin-like growth factor I treatment on the molecular distribution
      of insulin-like growth factors among different binding proteins.
AB  - The molecular distribution of insulin-like growth factor I (IGF-I) and IGF-II
      among the IGF binding proteins (IGFBPs) was studied before and during IGF-I
      therapy in Ecuadorean adults with growth hormone receptor deficiency (GHRD). Of
      the total circulating IGF-I and IGF-II, 70% was carried by the 150 kDa complex in
      normal subjects, while in patients with GHRD, 50% of serum IGF-I, but only 30-35%
      of serum IGF-II, was measured within the 150 kDa IGFBP-3 region. Administration
      of IGF-I altered the concentration of IGF-I and IGF-II, although the percentage
      of total IGF measured within each IGFBP region was not affected, as the increase
      in IGF-I and the decrease in IGF-II were proportional. Similarly, serum
      concentrations of IGFBP-3 and the acid-labile subunit, measured by
      radioimmunoassay, were unaltered. Thus, administration of IGF-I to patients with
      GHRD was unable to correct the aberrant distribution of IGFs among the IGFBPs.

PMID- 7524823
TI  - Gene expression of erythropoietin in hepatocellular carcinoma.
AB  - A 68-year-old man with hepatocellular carcinoma complicated by erythrocytosis
      showed an increased plasma level of immunoreactive erythropoietin (EPO). Northern
      blot analysis and RT-PCR (reverse transcriptase and polymerase chain reaction) of
      EPO mRNA extracted from a surgical specimen indicated high expression of EPO mRNA
      in the tumor tissue. Histological and immunocytochemical examination showed that
      the tumor was a hepatocellular carcinoma with predominant immunostaining for EPO.
      The erythrocytosis improved and the high serum EPO level decreased after
      resection of the tumor. This is the first demonstration of EPO mRNA expression in
      hepatocellular carcinoma tissue by RT-PCR.

PMID- 7524824
TI  - Three-dimensional view of a selectin cell adhesion molecule.

PMID- 7524825
TI  - Multivalent sialyl-LeX: potent inhibitors of E-selectin-mediated cell adhesion;
      reagent for staining activated endothelial cells.
AB  - Free, monovalent, SLeX (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)-GlcNAc), SLn
      (Neu5Ac alpha 2-3Gal beta 1-4GlcNAc) and corresponding BSA-conjugated forms-
      displaying different ratios of SLeX and SLn to protein--were tested for their
      ability to inhibit binding of HL-60 cells to immobilized E-selectin. Free SLeX
      and conjugated SLeX-BSA inhibited cell binding in a dose-dependent manner. SLn
      and SLn-BSA did not inhibit binding. SLeX16BSA (16 mol tetrasaccharide/mol BSA)
      and monovalent SLeX inhibited cell binding with measured inhibitory
      concentrations (IC50S) of 1 microM and 1 mM, respectively, demonstrating a three
      order-of-magnitude enhancement of inhibitory activity with the multivalent form
      of SLeX. A SLex7BSA conjugate was 10-fold less potent than those with 11 or 16
      mol SLeX/mol BSA. An assay which measured neutrophil rolling on interleukin (IL)
      1 beta-activated human umbilical vein endothelial cells (HUVECs) showed 50%
      reduction in the number of rolling neutrophils in the presence of 1 microM
      SLeX16BSA, whereas the level of free, monovalent SLeX oligosaccharide required to
      produce the same effect was approximately 0.3 mM. SLeX-BSA was found to be an
      excellent reagent for staining endothelial cells expressing E-selectin.
      Biotinylated SLeX-BSA in conjunction with Texas red avidin-stained
      lipopolysaccharide (LPS)-activated HUVECs, and co-incubation of activated cells
      with anti-E-selectin, specifically blocked staining. The distribution of E
      selectin, as determined by binding of SLeX-BSA, was virtually identical with that
      obtained by binding of anti-E-selectin antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524826
TI  - Novel antigenic determinants from peptidorhamnomannans of Sporothrix schenckii.
AB  - Antisera were raised in rabbits against acetone-dried yeast-like and mycelium
      forms of Sporothrix schenckii. These antisera were tested for immunoprecipitation
      of peptidorhamnomannans isolated from both cell types. Both antisera reacted
      strongly with S.schenckii peptidorhamnomannans, but the reactions were weak with
      beta-eliminated peptidopolysaccharides. These antisera did not recognize the
      Saccharomyces cerevisiae mannoprotein, and reacted poorly with Ceratocystis
      (Ophiostoma) stenoceras cell wall glycopeptides. Since beta-eliminated
      glycopeptides were poorly reactive, we investigated the activity of O
      glycosidically linked oligosaccharides which were liberated from the
      peptidorhamnomannans by mild alkaline hydrolysis, using a hapten inhibition test.
      The rates of inhibition showed that the immunodominant epitopes in O-linked tetra
      and pentasaccharides had the following novel structures: alpha-L-Rhap (1-->4)
      alpha-D-GlcpA and alpha-L-Rhap(1-->4)-[alpha-L-Rhap(1-->2)]alpha-D-GlcpA .
      Results suggest that peptidorhamnomannans or synthetic antigens bearing these
      epitopes should be used for the specific detection of anti-S.schenckii antibodies
      rather than the long-chain N-linked polysaccharides.

PMID- 7524827
TI  - Fractal properties of ion channels and diffusion.
AB  - We focus our attention on a fractal model recently proposed by Liebovitch to
      account for the lack of a time scale in ion channel kinetics. We establish a
      connection between the dwell-time distributions and the correlation time of the
      ion channel signal, thereby making it possible to derive analytical predictions
      on the diffusion properties of a random walk constructed from the sum of the
      current fluctuations of ion channels. With the help of a numerical simulation of
      the Liebovitch model, it is shown that the Hurst analysis can provide a reliable
      determination of the standard (or anomalous) diffusion properties. On the basis
      of results of computer simulation we argue that by applying the Hurst analysis to
      the experimental distribution of closed times it is possible, in principle, to
      establish whether the Liebovitch model is valid.

PMID- 7524829
TI  - The superiority of UW solution for maintaining ATP concentrations during
      pulmonary preservation.
AB  - We evaluated three solutions used for preserving lungs, namely, University of
      Wisconsin (UW), Euro-Collins (E-C), and low potassium dextran (LPD), by measuring
      the high energy phosphates in the preserved lung tissue. The left lungs of
      Sprague-Dawley rats were excised and flushed with 5 ml of one of the solutions at
      10 degrees C through the pulmonary artery, after which they were deflated and
      immersed in the solution at 10 degrees C for 24 h. The tissue adenosine
      triphosphate (ATP) concentration in mumol/g tissue wet weight after 24 h of
      storage was 2.55 +/- 0.48 (n = 7) in the UW lungs, 1.98 +/- 0.25 (n = 6) in the E
      C lungs, and 1.53 +/- 0.32 (n = 4) in the LPD lungs, being significantly higher
      in the UW lungs than in either the E-C or LPD lungs (P < 0.05). The
      histopathological findings of the E-C lungs were more deteriorated, with marked
      interstitial edema, septal hypertrophy, and perivascular hyaline degeneration,
      than either the UW or LPD lungs. Thus, the findings of this study indicate the
      superiority of UW solution for lung preservation.

PMID- 7524830
TI  - Clinical significance of serum alpha-fetoprotein subfractionation in pediatric
      diseases.
AB  - Serum alpha-fetoprotein (AFP) subfraction profile is a predictive indicator for
      the discrimination of hepatic malignancies, benign liver diseases and yolk sac
      tumor in adults. In the present study, AFP subfractions were examined in AFP
      positive sera from 59 patients of less than 15 years of age. Fractionation of AFP
      was carried out by lectin affinity crossed-line immunoelectrophoresis.
      Concanavalin A, Lens culinaris hemagglutinin and phytohemagglutinin E were used
      as lectins. Fifty-four of 59 (91.5%) AFP subfraction profiles in patients with
      pediatric diseases were classified into three common types: (1) benign liver
      disorder, (2) hepatic malignancy and (3) yolk sac tumor. An atypical AFP
      subfraction profile resembling hepatic malignancy type was found in 5 of 59
      (8.5%) infants. It was concluded that estimation of serum AFP subfraction
      profiles facilitates differential diagnosis of various AFP-positive pediatric
      diseases, such as hepatoblastoma, hepatoma, hepatic cirrhosis, hepatitis or germ
      cell tumors.

PMID- 7524828
TI  - Lindane embryotoxicity and differential alteration of cysteine and glutathione
      levels in rat embryos and visceral yolk sacs.
AB  - The lindane embryotoxicity and associated changes in cysteine (CYS) and
      glutathione (GSH) status have been investigated in the early organogenesis-stage
      rat conceptus utilizing whole embryo culture techniques. Direct exposure of
      gestational day 10 (GD 10) conceptuses to lindane (50, 100, 200, 300, and 400
      microM) in the culture medium resulted in a dose- and time-dependent increase in
      mortality (88% at 400 microM), frequency, and severity of malformations and in
      decreased growth parameters. Protein and DNA contents of embryo and visceral yolk
      sac (VYS), likewise decreased significantly as lindane concentrations increased.
      Lindane exposures greater than 100 microM produced abnormal axial rotation,
      pooled blood on lateral cephalic surfaces, cephalic edema, and decreased VYS
      vasculature. Histologic sections showed a variety of abnormalities, including
      distended anterior cardinal veins, thinning of the neuroepithelium in forebrain
      and hindbrain regions, and abnormal branchial arch development. CYS and GSH
      levels in the VYS were not significantly affected by 100 microM lindane exposure
      during a 5-h incubation period on GD 10 and GD 11. In contrast, CYS and GSH
      levels in lindane-exposed embryos remained unchanged while control levels
      continued to increase with gestational age. At 5 h, treated embryos showed a
      significant depletion of CYS (GD 10, 22%; GD 11, 35%) and GSH (GD 10, 41%; GD 11,
      24%) relative to controls. Selective lindane-induced depletion of embryonic GSH
      suggests involvement of the glutathione redox cycle in lindane embryotoxicity.

PMID- 7524832
TI  - [Graduated quantitative diagnosis of spleen deficiency syndrome].
AB  - 90 Cases with Spleen Deficiency Syndrome (SDS) in various diseases of different
      body system were studied to obtain a quantitative measurement of the syndrome for
      more accurate diagnosis. Rates of symptom manifestation of SDS, absorptivity of D
      xylose, activity of salivary amylase, hemoglobin level, RBC count, plasma
      albumin, cardiac function as well as some parameters of hemorheology and
      lymphocyte transformation rate were observed. The results clearly showed that the
      D-xylose absorptivity was much lower in patients with higher appearance rate of
      SDS symptoms, which was dose-dependent. Along with the lowering of D-xylose
      absorptivity, the values of above-mentioned parameters dropped were positively
      correlated to it. On the contrary, the peripheral vascular resistance elevated as
      D-xylose absorptivity dropped. The author divided the SDS into three stages as a
      graduated quantitative diagnosis based on the drop of D-xylose absorptivity, the
      increase of SDS symptom and other changes of laboratory findings.

PMID- 7524831
TI  - Changes in platelet membrane glycoproteins and platelet-leukocyte interaction
      during hemodialysis.
AB  - Platelet aggregation and interaction with other vascular cells play a key role in
      hemostatic events during hemodialysis. We studied seven patients with end-stage
      renal failure on long-term hemodialysis treatment. Flow-cytometric techniques and
      platelet-specific monoclonal antibodies were used to measure the platelet surface
      expression of glycoproteins-fibrinogen receptor on glycoprotein IIb-IIIa (GP IIb
      IIIa; CD41) and alpha-granule membrane protein (GMP-140; CD62). In addition,
      adhesion of platelets or platelet microparticles with leukocytes was evaluated by
      appearance of the platelet-specific antigen (GP IIb-IIIa) on leukocytes. Blood
      samples were taken before the start of dialysis and 15, 60, and 240 min
      thereafter. There was a significant increase in fibrinogen receptor activation on
      circulating platelets after 15 min of dialysis treatment (P < 0.001) and enhanced
      degranulation of GMP-140 (P < 0.05). In parallel, the interaction of platelets
      with neutrophils and monocytes also increased with the duration of dialysis and
      was maximal after 15 min (P < 0.001). We conclude that the platelet fibrinogen
      receptor on GP IIb-IIIa in circulating platelets is activated during hemodialysis
      and is associated with increased adhesion of platelets or platelet microparticles
      with circulating leukocytes. Thus, the phenomenon described here of platelet
      leukocyte interaction could be pathophysiologically important for the development
      of dialysis-associated leukopenia.

PMID- 7524833
TI  - [Comparison of 2 6% middle-molecular hydroxyethyl starch solutions on elimination
      kinetics and flow characteristics of blood in volunteers].
AB  - OBJECTIVE: Investigation of the influence of C2/C6 occupation ratio of 2
      different 6% hydroxyethyl starch (HES) solutions on elimination kinetics and
      blood fluidity. DESIGN: A single-blinded, prospective randomised cross-over
      study. SETTING: Haemostasiological-angiologic outpatient department of the
      university of Homburg. SUBJECTS: 6 voluntary apparently healthy subjects.
      INTERVENTIONS: A 500 ml infusion of 2 different HES solutions (6% HES 200/0.5 or
      6% HES 200/0.62, respectively) was given intravenously within 1 h. A wash-out
      phase of 3 months was kept between both infusions. The concentration and
      distribution of the molecular weight of the intravasal HES molecules up until 24
      h after the infusion as well as the blood fluidity before and after the infusion
      were measured. RESULTS: Besides the molecular substitution (MS), which is
      different for the 2 employed HES solutions, the occupation ratio of the C2
      respectively C6 (C2/C6 occupation ratio) of the glucose ring influences the
      breakdown of the HES molecules. This influences the blood fluidity. While the
      decrease in haematocrit 1 h after the end of the infusion is comparable, the
      decrease in the haematocrit in the case of high C2/C6 occupation ratio and a high
      MS is maintained for a longer period of time. The increase in plasma viscosity in
      the case of high C2/C6 occupation ratio and high MS is more marked. CONCLUSIONS:
      The infusion of HES 200/0.62 leads to a significantly longer prevalence in
      comparison to HES 200/0.5, in combination with clearly larger degradation
      products in the plasma; this fact causes a more marked dilutional effect, but
      also a more marked increase in the plasma viscosity up to 24 h after the end of
      infusion. In the discussion on haemodilution therapy in patients with arterial
      occlusive disease the employment of HES which induces an increase in plasma
      viscosity is thought to be a disadvantage.

PMID- 7524834
TI  - Genetic analyses of cell-matrix interactions in development.
AB  - The extracellular matrix and its cell surface receptors are thought to be
      important in development. Recent applications of targeted mutagenesis in mice
      have begun to test hypotheses based on in vitro data and patterns of expression.
      'Knockout' mutations of matrix molecules and integrins reveal complexities
      arising from multiple receptors and ligands.

PMID- 7524835
TI  - In vitro sensitivity of human melanoma cells to chemotherapeutic agents and
      interferons.
AB  - The purpose of our study was to evaluate systematically the anti-proliferative
      effects of eight chemotherapeutic drugs as well as of four recombinant
      interferons (IFNs) (alpha-2a, alpha-2b, beta, gamma). All drugs and IFNs were
      tested separately and in combination at several concentrations on four human
      melanoma cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5,
      diphenyltetrazolium (MTT) test. In all cases, drug inhibitory concentrations of
      chemotherapeutic agents required to kill 25% of melanoma cells (IC25) in vitro
      were in the range of the maximal achievable plasma peak level in vivo.
      Sensitivity to the anti-proliferative action of bleomycin, DTIC, doxorubicin,
      cisplatin and carboplatin was similar for all melanoma cell lines, whereas cell
      lines exposed to 5-fluorouracil (5-FU), vindesine and fotemustine differed up to
      26-fold in their sensitivity. Studies with IFN showed that IFN-beta and IFN-gamma
      proved to be more antiproliferative than IFN-alpha in a dose-dependent fashion in
      all cell lines. However, the ability of IFNs to improve cytotoxicity of
      chemotherapeutic agents was limited. Pre-incubation of melanoma cells with IFN as
      well as exposure to IFN after incubation with the drugs showed mainly additive
      effects (231/256). These results confirm the high chemoresistance of human
      melanoma cells, independently of the drug chosen. Combinations of
      chemotherapeutic agents with IFN will provide additional therapeutic benefit, but
      are unlikely to change the overall high chemoresistance of human melanoma cells.

PMID- 7524836
TI  - T cell recognition of haptens, a molecular view.
AB  - Our review attempts to summarize the present knowledge on how T lymphocytes
      recognize chemically modified autologous cells. Concerning the broad spectrum of
      chemically and drug-induced allergic and autoimmune diseases, the molecular
      mechanisms of hapten recognition by T cells are clearly of more than academic
      interest. The past few years revealed that in contrast to the expectations of
      many researchers, major histocompatibility complex (MHC)-restricted hapten
      specific T cell receptors in their majority do not react to covalently modified
      MHC molecules, but to haptenized peptides associated with the MHC peptide-binding
      groove. This finding allowed the introduction of synthetic hapten-peptide
      conjugates, the MHC specificity of which may be predetermined by allele-specific
      peptide sequence motifs. Thus, it has now become feasible to selectively hapten
      modify defined sets of MHC molecules on living cells, and to study their
      immunological properties. In that way two major types of hapten-specific T cell
      receptors were identified: one reacting to hapten without caring for the chemical
      composition of the carrier peptide, and the other contacting hapten and peptide
      by two apparently independent contact sites. The consequences of these findings
      for hapten-specific allergies and autoimmunities, but also for our molecular
      understanding of antigen recognition by T cells are discussed.

PMID- 7524837
TI  - Discordant expression of LFA-1, VLA-4alpha, VLA-beta 1, CD45RO and CD28 on T-cell
      subsets: evidence for multiple subsets of 'memory' T cells.
AB  - Several adhesion molecules and CD45RO have been reported to be upregulated on the
      cell surface of 'memory' T cells. Using triple-color flow cytometry, we compared
      the levels of typical 'memory' cell markers on peripheral blood T-cell
      subpopulations in a number of kidney transplant recipients, patients with
      systemic lupus erythematosus, newborn infants and healthy donors. CD45RO, VLA
      beta 1 (CD29), VLA-5 alpha (CD49e), LFA-1 (CD11a/18), and CD2 were found to be
      closely coregulated on CD4+ T cells, while regulation of VLA-2 alpha (Cd49b), VLA
      4 alpha (CD49d) and CD44 was quite discordant. In CD8+ T cells, by contrast,
      multiple subsets of 'memory'-type cells were distinguished. Unlike TCR alpha/beta
      T cells, which expressed either high or low levels of LFA-1, TCR gamma/delta
      cells all expressed high levels of LFA-1 (CD11a/CD18). Examination of T cells
      from kidney graft fine-needle aspiration biopsies during rejection revealed
      intragraft accumulation of 'memory'-type T cells expressing high levels of CD2
      and LFA-1 (CD11a/CD18). Regarding peripheral blood T-cell subsets, differences
      between patients and healthy controls were only of a quantitative nature.

PMID- 7524838
TI  - Maternal serum screening.
AB  - Maternal serum screening (MSS) measures three serum markers: alpha-fetoprotein,
      human chorionic gonadotropin, and unconjugated estriol, from which the risk of
      fetal Down syndrome or open neural tube defect is calculated. Initially, 8% of
      women will have positive results. I present a protocol for investigating these
      women. Family physicians should be informed about MSS so they can give their
      patients information and guidance.

PMID- 7524840
TI  - Palliative care.

PMID- 7524839
TI  - Maternal serum screening in the Sioux Lookout Zone. Complicated test for an
      unspecified need.
AB  - We investigated whether the incidence of fetal abnormalities among patients in
      Sioux Lookout Zone differs from incidence elsewhere in Canada, whether First
      Nations people would agree to screening, how information could be disseminated,
      and what practical considerations would affect implementation. Incidence appears
      to be similar to elsewhere, but First Nations people's cultural and spiritual
      beliefs and the difficulty of taking action once results are confirmed make
      current screening programs inappropriate.

PMID- 7524841
TI  - CD34+ positive haemopoietic cells: biology and clinical applications.
AB  - CD34+ is a heavily glycosylated surface antigen which is preferentially expressed
      on haemopoietic stem/progenitor cells. No definitive function has been attributed
      to CD34+, but it appears to play a role in cell to cell adhesion and may be
      involved in signal transduction to regulate the expression of other haemopoiesis
      associated genes. A number of monoclonal antibodies to CD34+ have been raised and
      these have allowed the identification and characterization of a whole range of
      haemopoietic progenitor cells. CD34+ is expressed most strongly on the most
      primitive cells and is progressively lost as cells differentiate. The restricted
      expression of CD34+ to haemopoietic stem/progenitor cells has been exploited for
      transplantation studies. Several techniques have been developed to select cells
      expressing CD34+ from haemopoietic tissues. Successful sustained engraftment can
      be achieved using such positively selected cells. Alternatively, CD34+ cells may
      be expanded in vitro by incubation with synergistic cytokine combinations before
      being re-infused. An exciting new development has been the use of purified
      populations of CD34+ cells as the targets for gene marking and gene therapy
      protocols.

PMID- 7524842
TI  - [Ecological influences on the health status of small-size populations of the
      North].
AB  - The paper gives the results of examining the ecological impact on the health of
      the native populations of the North, shows the influence of drastic changes in
      the traditional lifestyle of the natives on the prevalence and specific features
      of the course of major diseases in the North. The ecological situation rapidly
      changing in the areas of large-scale economical development has influences on
      human regulatory systems in the North.

PMID- 7524843
TI  - [Immunological mechanisms of the formation of ecologically-induced pathology].
AB  - The paper provides the results of examining about 3,000 industrial workers
      exposed to various xenobiotics. Various phases of immune responses were noted in
      40-60% of persons with nonspecific chronic pulmonary, gastrointestinal,
      gynecological diseases at remission. 10-20% of the industrial workers under study
      were diagnosed as having secondary immunodeficiency whose criteria were the
      presence of one of clinical syndromes, a sharply significant reduction in
      immunoglobulins, normal levels of circulating immune complexes and normal values
      of the lymphocytic enzymes alpha-glycerophosphate dehydrogenase, succinate
      dehydrogenase, lactate dehydrogenase. The stimulation of the immune system in
      clinically healthy individuals who have a service length of 3 year or more should
      be regarded as development of an immune response to a xenobiotic or its
      metabolites.

PMID- 7524847
TI  - [Opening address of Academician V. I. Pokrovskii, President of the Russian
      Academy of Medical Sciences].

PMID- 7524846
TI  - [Comprehensive hygienic studies in the industrial Arctic regions: prospects].

PMID- 7524845
TI  - [Role of apo B-containing lipoproteins in the development of exertional diabetes
      in humans under Arctic and Antarctic conditions].
AB  - Under extreme conditions of the Arctic and Antarctic, man develops exertional
      diabetes, which is characterized by (1) decreases in blood insulin levels and in
      responses of the insular apparatus to glucose load; (2) a reduction in blood
      sugar; (3) a drop in glucose uptake; (4) lowering of the renal barrier for blood
      sugar and other low-molecular weight compounds; (5) appearance of urinary sugar
      and an increase in its nocturnal resting concentration. Exertional diabetes lies
      in the basis of switching energy metabolism from the carbohydrate to lipid types
      at high latitudes. The mechanism of this phenomenon is associated with the contra
      insular effect of LDL and VLDL. There is a common epitope in the beta-chain of
      insulin and LDL and VLDL apoprotein B. The existence of the common epitope leads
      to competition of insulin and apoprotein B for an insulin receptor and reduces
      tissue glucose uptake.

PMID- 7524844
TI  - [Healing effects of several ecological exposure factors on the lymphatic system].
AB  - The structural and functional responses of lymph nodes to environmental
      influences have common stereotypic features; however, they can vary with the
      nature of an influencing factor and the functional specialization of the lymph
      node. In this view, the morphological and functional status of lymph nodes can be
      regarded as markers of environmental impact on the lymphatic system. Approaches
      to correcting blood and lymph circulation have been developed via combined
      exposure of the body's internal environment to sorbent therapy, balneological
      procedures at the Siberian resorts, biological flavonoids, and derivatives of
      Siberian raw plant materials.

PMID- 7524849
TI  - [Social-hygienic problems of child morbidity and infant mortality in Omsk].
AB  - The morbidity rates in infants in Omsk are higher than those in other areas of
      the country. In its pattern, respiratory diseases (chronic non-specific lung
      diseases) head the list, peaking in infants of 2 years of age, which is largely
      associated with the presence of a large-scale petrochemical integrated works. The
      infantile mortality changes occurring in the past 15 years are characterized by a
      downward trend, which is associated with medical organizational measures.

PMID- 7524850
TI  - [Role of migration processes in oncologic epidemiology of Siberia and Far East].
AB  - The paper presents the analysis of the cancer death rates among the population of
      a Norilsk industrial area and compares the rate and structure among newcomers and
      natives. The persons who long live in this area more frequently die of cancer
      diseases than migrants. They have high mortality rates for most sites (the
      stomach, esophagus, bowel, liver, pancreas). The migrants die younger and chiefly
      of tumors of respiratory organs, the skin, brain, and female genitals. The lower
      mortality rates in the newcomers are attributable to their departure to their
      former residence places.

PMID- 7524851
TI  - [Dynamic estimation of mental health in native and newcomer population of the
      Siberian North].
AB  - Clinical and epidemiological studies of the population (the indigenous, the
      aliens, the migrants) in the Siberian North have shown it promising to develop a
      regional aspect of modern psychiatry and narcology. There is a high prevalence of
      borderline states and alcoholism among the natives and migrants. Specific
      features of the clinical picture of many types of borderline abnormalities have
      been found. The traditional criteria are of relative significance in the
      determination of the mental health and it is essential to revise the existing
      strategy of specialized psychiatric and narcological care.

PMID- 7524853
TI  - [New ecological aspects of extraorganism pathogenic microbial populations].
AB  - The author summarizes the results of his own studies of pathogenic microorganisms
      and saprophytes, their intertransitional forms. The environmental pathogenic
      bacteria have been demonstrated to be autotropic, but in man and warm-blooded
      animals the organisms act as heterotrophic. This explains their wide range of
      metabolic plasticity and smooth distinction of saprophytes and parasites.

PMID- 7524852
TI  - [Socio-medical aspects of injuries on the Baikal-Amur main line].
AB  - In the past 10 years, the total rate of traumatism on the Baikal-Amur main line
      has reduced by 15% at the expense of occupational traumatism, whereas the rate of
      non-occupational injuries is on the rise. Males (86%) are prevalent among the
      victims. The most all-bodied persons (aged 21-40 years) account for 85.1%. Friday
      and Saturday are the days marked by 33.5% of all injuries. The injury pattern is
      changing for the worse. The incidence of fractures of the skull and spine is on
      the increase. This leads to an increase in treatment length. The influence of
      some sociohygienic factors on the traumatism of workers (Mostostroy Trust, Tynda;
      Aluminum-Producing Plant, Shelekhov) is being comprehensively studied. The
      results will allow the administers to be proposed concrete recommendations to
      reduce traumatism rates.

PMID- 7524848
TI  - [Health status of schoolchildren in industrially developed and rural areas of
      West Siberia].
AB  - Medical examinations of the schoolchildren living in West Siberian urban and
      rural ares have revealed a high prevalence of chronic diseases and functional
      abnormalities. Children referring to health groups I and II were not found. This
      makes it necessary to perform such studies as a component of medical and
      ecological monitoring and as the basis for children's health promotion.

PMID- 7524854
TI  - [Effects of external biophysical factors on reproducibility of Escherichia coli
      characteristics].
AB  - The paper gives the results of examining the influence of external biophysical
      factors (inoculate's age, inoculative dose, cultivating temperature) on the
      reproducibility of changes in the formation of intercellular biophysical
      processes in the bacterial population. The conditions under which there is a high
      reproducibility (the error being 5-7%) of development dynamic parameters for E.
      coli are shown to be the age of an inoculate, 24 hours, the cultivating
      temperature, 24 degrees C, the inoculative dose is the dose corresponds to the
      baseline optical density of working liquor in the range of 0.025-0.050.

PMID- 7524855
TI  - [Scientific concept of providing Russian population with drugs].

PMID- 7524856
TI  - [Microsurgical and endoscopic laser diskectomy in osteochondrosis of the lumbar
      spine].
AB  - Experimental studies have revealed that a pulse surgical laser based on alumo
      yttrium garnet with neodymium ensures bloodless diskectomy and evaporation of a
      pulposus nucleus in the volume sufficient for decompression of the intervertebral
      disk. Biomechanical studies of spinal resistance following puncture endoscopic
      laser decompression of the intervertebral disk (PELDID) and microsurgical laser
      diskectomy (MLD) have demonstrated that these surgical interventions fail to
      disturb the stability of the spinal portion operated on. A total of 75 patients
      with radicular syndrome were operated on with the proposed procedures: 32 with
      PELDID and 43 with MLD. The subsequent studies have shown that 69 (92%) patients
      returned to previous work at week 7 and 5 (6.7%) at week 9 of postoperation. The
      major manifestation of radicular syndrome--leg pain--was eliminated in 100% after
      MLD and in 96.9% after PELDID.

PMID- 7524858
TI  - [Common mechanisms of cardiac damage and adaptation in ischemia and reperfusion
      (components for the construction of the general theory of cardiac pathology)].
AB  - The paper deals with the common cellular and molecular mechanisms responsible for
      the development of cardiac abnormalities of various genesis. These include
      changes in cardiomyocytic energy supply processes; physicochemical states and
      structures of their membranes, in myocardial cell enzymatic activity, intra- and
      extracellular concentrations and ratios of ions to fluid, in cardiomyocytic
      electrophysiological parameters, their genetic programme and/or mechanisms of its
      implementation, in cardiac neurohumoral regulation. It also outlines the specific
      intra- and extracardiac mechanisms of adaptation of the heart in its lesion of
      various origin.

PMID- 7524857
TI  - [Formation of pathological anatomy at the Moscow University].

PMID- 7524859
TI  - [Intercellular interactions in glomerulopathies].

PMID- 7524860
TI  - [Current status of laboratory diagnosis of infections caused by nonspore-forming
      anaerobes and ways of its improvement].
AB  - Nonspore-anaerobic bacteria are the most common pathogens of purulent
      opportunistic infection. However, this group of infections is not recorded in our
      country due to the lack of national culture media and special laboratory
      equipment for anaerobic bacteriology. The laboratory diagnosis of infections
      caused by nonspore-forming anaerobes are analyzed and urgent measures to solve
      this topical problem are defined.

PMID- 7524862
TI  - [Good traditions, new approaches].

PMID- 7524861
TI  - [Pathogenetic rationale and basic principles in the comprehensive detoxifying
      therapy of purulent peritonitis].
AB  - The multimodality therapy for patients with purulent peritonitis and Degrees II
      III endotoxicoses involves efferent methods of detoxification and hemocorrection
      alone and in combinations with hemosorption (HS), plasmapheresis (P), ultraviolet
      autoblood radiation (UVAR), immunocorrection through extracorporeal donor
      xenosplenic inclusion (EDXSI) or xenoperfusate infusion (XPI), indirect
      electrochemical detoxification (IECD) of blood and exfused plasma by the use of
      sodium hypochlorite (NaClO) obtained on an EDO-1 electrochemical unit. The
      analysis of therapeutical results has indicated that the efferent methods should
      be included into the multimodality therapy only in Degrees II-III endotoxicoses
      when a considerable number of toxic components leading to the development of
      organ- and system-specific insufficiency accumulate in the patients' circulatory
      systems. With this, the obligatory conditions are an adequate sanitation of the
      abdomen with the topical application of NaClO as an antiseptic and a
      fibrinolytic, rational antibacterial and homeostatic corrective therapy. The
      combined use of the efferent methods (HS+UVAR; HS+XPI; P+IECD of plasma) in the
      programmed mode is pathogenetically grounded, which produces a potentiating
      detoxifying effect, and levels the negative aspects of each method alone. P is
      preferable when it is used alone (in case of adequate plasma replacement. A
      comprehensive therapy policy has been developed in accordance with the stage of
      peritonitis and the degree of endotoxicosis.

PMID- 7524863
TI  - [Current concepts in observation and treatment of patients with internal
      endometriosis of the uterus].
AB  - The paper outlines the issues of improving and systematizing clinical
      instrumental diagnostic and therapeutical techniques for internal endometriosis.
      The results of examining 220 patients with internal endometriosis, out of whom
      116 were further operated on, have been prospectively and retrospectively
      studies. Based on the histological findings of the gross specimens
      intraoperatively removed, the authors analyzed the predictive value of clinical
      and instrumental diagnostic criteria, including those of transvaginal echography,
      Doppler echometry of the arteries supplying the uterus, those of hysteroscopy and
      the computer hysterosalping graphic technique developed by them. The ovarian
      morphological and receptor apparatuses were studied in internal endometriosis.
      The examination and treatment system for patients with internal endometriosis is
      presented in the paper.

PMID- 7524864
TI  - [Regularities of differentiation of lymphoid structures in the walls of hollow
      internal organs of man].
AB  - The regularities of the structure of lymphoid tissue in the hollow visceral walls
      were found while analyzing the results of studies conducted in the author's
      laboratory by examining a lot of materials--corpses of the individuals who had at
      their death had no inflammatory or other diseases which could greatly affect the
      structure of immune organs. In the walls of digestive, respiratory, and urinary
      organs, the author followed up the development of lymphoid structures from the
      lymphoid cells diffusely scattered in the mucosa to the accumulation of these
      cells and formation of lymphoid nodules with and without reproduction centers. He
      also analyzed the causes promoting the concentration of lymphoid cells as
      aggregates, the formation of lymphoid nodules in the viscera having their
      different structure and uses.

PMID- 7524865
TI  - [Matrix endoprostheses for replacement of the tendon-ligament system].
AB  - A classification of tendinous and ligamentous implants has been proposed on the
      basis of their baseline and final strength, taking into account the matrix
      properties of a material. The experiments on the knee joints and Achilles tendons
      of laboratory animals have revealed the matrix properties of carbon-containing
      fiber. Biological reconstruction of tendon ligaments occurs in parallel to the
      degradation of biodestructive carbon-carbonic fiber (BCF) which is absent in the
      Vitlana (polymer carbon fiber) implants. The expediency of extra- and
      intraarticular implantation of the Vitlana and extraarticular one of BCF has been
      evidenced. The use of the Vitlana implants is found justifiable to replace
      Achilles tendon defects. Due to the occurrence of complications, it is not
      advisable to use BCF for intraarticular management of and plastic operations for
      Achilles tendon defects.

PMID- 7524866
TI  - [Hemodynamic and rheologic aspects of the pathogenesis and prevention of
      cerebrovascular diseases].
AB  - Ultrasonography was used to study carotid and central hemodynamics in patients
      with cerebrovascular diseases and to analyze the factors responsible for
      reduction of cerebral blood supply. Comparative studies of the regulatory system
      for blood aggregation in patients elucidated the contribution of the system to
      the pathogenesis of cerebral hemorrhage and ischemia, defined the modes of
      preventing hemorrhagic and ischemic events in cerebrovascular diseases. The
      authors also discussed pathogenetic and prophylactic aspects of the diseases in
      childhood.

PMID- 7524867
TI  - [Neurophysiologic analysis of the effects of the centrally acting analgesics
      moradol, tramal and nubain].
AB  - The analysis of measurements of early and late components of somatosensory (SSEP)
      and visual evoked potentials (VEP) in healthy examinees was used to compare the
      central mechanisms responsible for the analgesic action of moradol, tramal, and
      nubain. As compared to tramal and nubain, moradol was found to cause a more
      profound increase in the amplitude of early SSEP components. With this, all three
      agents were equal in suppressing the amplitude of late SSEP and VEP components.
      The effects of the drugs on SSEP and VEP, as well as on the sensory and
      psychoemotional components of human pain perception were also evaluated. The
      potential features of anesthesiological application of the drugs under study were
      discussed.

PMID- 7524868
TI  - [Medical and economic problems in the reform of health maintenance].
AB  - The paper summarizes the results of comprehensive studies into the management
      efficiency of therapeutical-and-prophylactic institutions under new economic
      relations in this area. Transition to public health insurance changes the
      relations between the system's subjects, determines the need of standardization,
      pricing, and quality estimation of medical services. The basic directions of the
      health perform are defined.

PMID- 7524870
TI  - [Genetic monitoring of mutational events in human populations at the DNA level].
AB  - It was elaborated the new method of genetic monitoring of human populations at
      DNA level. Mutation events in the VNTR regions of DNA were registered by
      comparison of fingerprint bands after Southern blot-hybridisation. The multilocus
      minisatellite probe Red4 was used for detection of VNTR. If there is an
      additional band in the DNA fingerprint of a child in comparison with fingerprints
      of both parents, it was considered as a new mutation in the germ cell of a
      parent. The study of the spontaneous level of mutations in the VNTR regions
      showed that there were no differences in the number of fingerprint bands both
      between males and females and between parents and children. The average number of
      bands was equal to 21.59 + 5.63 for the parents, and 21.83 + 5.33 for children.
      The frequency of mutation (per band/per child) was 0.0081, the number of mutation
      per individual was 0.178. For registration of two-fold increase of mutation
      frequency it is necessary to have at least 113 persons (and their parents) in
      each group, but for a 50% increase at least 304 persons.

PMID- 7524869
TI  - [Basic trends in general human pathology and principles of its teaching in higher
      medical education].
AB  - The paper considers the current trends in the development of biological and
      medical sciences: their subject, tasks, methods, and place of General Human
      Pathology among other subjects, its value for the clinical discipline. It defines
      and analyzes the most topical and disputable directions of General Human
      Pathology, primarily including those which form the bases for the pathology
      theory. Arguments are advanced for the necessity of introducing the subject
      General Pathology of Man into the curriculum of higher medical educational
      establishments at various faculties. Consideration is given to the specific
      features of this subject teaching at the faculty training researchers and
      research pedagogical personnel, at the Pharmaceutical and Higher Nurse Training
      Faculties of the I. M. Sechenov Moscow Medical Academy. A proposal is given to
      consider and to discuss the most important problems of General Pathology and its
      teaching, which are listed in the paper.

PMID- 7524871
TI  - Treating benign prostatic hyperplasia with medications.

PMID- 7524872
TI  - Are the days of transurethral resection of prostate for benign prostatic
      hyperplasia numbered? Urologists must grasp the future.

PMID- 7524873
TI  - Are the days of transurethral resection of prostate for benign prostatic
      hyperplasia numbered? Alternatives are still unproved.

PMID- 7524874
TI  - High prevalence of serum antibodies to hepatitis C virus in patients with
      Hashimoto's thyroiditis.

PMID- 7524875
TI  - Hepatitis C in asymptomatic British blood donors with indeterminate
      seropositivity.

PMID- 7524876
TI  - Hepatitis C and injecting drug use in prisons.

PMID- 7524877
TI  - Care of dying patients in hospital. Guidelines may have improved care.

PMID- 7524878
TI  - Care of dying patients in hospital. Palliative care teams have helped.

PMID- 7524879
TI  - Care of dying patients in hospital. Things have improved.

PMID- 7524880
TI  - Care of dying patients in hospital. Carers need support.

PMID- 7524881
TI  - Parotid saliva composition during and after irradiation of head and neck cancer.
AB  - Parotid saliva composition was studied before, during and up to 18 months after
      the irradiation period in 16 cancer patients treated for malignancies in the head
      and neck region. Stimulated parotid saliva was collected prior to radiotherapy
      and, when possible, weekly during treatment. New samples were taken 2, 4, 6, 12
      and 18 months after the end of radiotherapy. Nine of the 16 patients were treated
      with bilateral irradiation fields and 7 patients with unilateral irradiation
      fields, with a total dose not exceeding 52 Gy. During the entire irradiation
      period the fraction of glands producing measurable volumes of saliva decreased to
      40%. In the postirradiation period the number of active glands gradually
      increased and saliva secretion rate returned to an average of 72% of the initial
      value 18 months after the end of irradiation. The concentrations of the measured
      variables increased already during the first week of radiotherapy and at the end
      of the treatment period the concentrations for total protein, salivary
      peroxidase, hexosamine and salivary IgA were significantly increased. The
      concentrations for total protein, salivary peroxidase and salivary IgA were still
      increased 6 months after the end of irradiation. At the 18-months observation all
      concentrations had returned to normal, as evaluated in a paired t-test. The
      majority of glands irradiated with 40-52 Gy recovered not only in secretion rates
      but also with respect to the components studied in this investigation.

PMID- 7524882
TI  - Central role of CD40 and its ligand in B lymphocyte responses to T-dependent
      antigens.
AB  - In order to mount an effective antibody response to soluble and certain other
      types of antigens, B cells need help from T cells. Recently, an important
      receptor-ligand pair has been identified as essential for successful cognate
      interaction between these two classes of lymphocytes. CD40 was first identified
      as a receptor-like molecule on B cells which when ligated by antibody could
      deliver signals to prime for growth, differentiation, or survival. Later its
      counterstructure--termed CD40 ligand (CD40L)--was discovered to be an inducible
      type II glycoprotein of helper T cells. In this review, the central role of the
      CD40-CD40L interaction in the various phases of the B cell response to T
      dependent antigens is discussed drawing from both in vitro and in vivo studies.

PMID- 7524883
TI  - Immunogenicity of microbial peptides grafted in self immunoglobulin molecules.
AB  - The advent of genetic engineering has allowed for the expression and production
      of recombinant proteins carrying short immunogenic epitopes of foreign antigens.
      These antigenized molecules represent valuable tools to investigate the molecular
      basis of antigen fragmentation, generation and presentation of peptide to
      lymphocytes, the induction of epitope specific immunity and potentially the
      development of a new generation of vaccines. Recently, we expressed viral
      epitopes on immunoglobulin molecules by replacing the D segment of a variable
      region of the heavy chain (VH) gene with a B cell epitope from the V3-loop of HIV
      1 envelope protein, as well as a cytotoxic T lymphocyte (CTL) and a T helper
      epitope from influenza virus nucleoprotein and hemagglutinin, respectively. The T
      cell peptides generated from the immunoglobulin molecules produced by cells
      transfected with chimeric V genes, activated specific T cells as they do when
      generated from viral proteins. Possible practical applications for the
      development of prophylactic and immunotherapeutic reagents are envisioned for
      immunoglobulin molecules bearing foreign epitopes.

PMID- 7524884
TI  - Validation of a simple technique for the detection of abnormal mucosal cell
      replication in humans.
AB  - Abnormal intestinal crypt cell proliferation is considered to be an important
      early risk marker for colorectal cancer but measurement of the rate and spatial
      distribution of cell division by histochemical localization of DNA synthesis is
      labour-intensive and expensive. We developed and evaluated a simpler technique
      for measurement of these parameters using direct visual analysis of mitotic
      figures in microdissected crypts. The direct crypt analysis technique was applied
      to colorectal biopsies from patients with ulcerative colitis or no mucosal
      abnormality. A characteristic shift of cell division toward the intestinal lumen
      was detected in patients with ulcerative colitis. The direct method was validated
      using rats fed diets containing cellulose, or guar gum to stimulate mucosal cell
      proliferation. The crypt cell proliferation rate (CCPR) was measured by the
      metaphase-arrest technique and the results were compared with direct crypt
      analysis. There was a fivefold range of CCPR values at three sampling sites
      across the dietary groups. An excellent linear correlation between the results by
      the two techniques was obtained (r = 0.98; P < 0.001). In a second experiment the
      spatial distribution of dividing cells between five zones in colonic crypts,
      determined by the new method or by staining with BrdU, was compared. Good
      agreement was again achieved. Visual analysis of intact crypts is a valid
      technique for the measurement of crypt cell cytokinetics and it is particularly
      suited for use in a clinical environment.

PMID- 7524885
TI  - Protease-induced alteration of insulin-like growth factor binding protein-3 as
      detected by radioimmunoassay. Agreement with ligand blotting data.
AB  - Structural alteration of insulin-like growth factor binding protein-3 (IGFBP-3)
      resulting from limited proteolysis by one or more serine proteases in vivo was
      first described in the serum of pregnant women and in certain pathological
      conditions. Western immunoblotting has since been employed to detect the
      phenomenon in normal serum, using a polyclonal antibody raised against
      recombinant human IGFBP-3 and a highly sensitive technique of visualization by
      chemiluminescence. The major proteolytic fragment of 30 kDa, which fails to be
      detected in native serum by ligand blotting owing to its weak affinity for IGFs,
      has proved clearly visible in all serum samples tested, sometimes accompanied by
      smaller fragments of 20 and 16 kDa. Among the serum samples analysed, increasing
      proportions of proteolysed IGFBP-3 were found in the following order: acromegalic
      patients, normal subjects, GH-deficient patients, pregnant women. In RIAs done
      with the same antibody, many of the serum samples yielded dose-response curves
      which were not parallel with standard curves, with lower gradients. In the
      samples where measurements were possible, apparent IGFBP-3 levels proved lower in
      pregnant women (2.28 +/- 0.23 mg/l, mean +/- SEM) than in normal adults (4.26 +/-
      0.33 mg/l, P < 0.001). These observations, which contradict earlier reports of
      higher levels in pregnant women, suggest that the 30 kDa proteolytic fragment has
      a weaker affinity for the antibody than the intact IGFBP-3 (which in ligand- and
      immunoblotting appears as a characteristic 42-39 kDa doublet and which is barely
      or not detectable in pregnancy serum).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524886
TI  - Decreased ternary complex formation and predominance of a 29 kDa IGFBP-3 fragment
      in human fetal serum.
AB  - Insulin-like growth factor-I (IGF-I) has been proposed to be important in the
      endocrine control of fetal growth in humans, although serum IGF-I concentrations
      are 10-fold lower than during rapid pubertal growth. However, the bioavailability
      of IGF-I in fetal serum may be increased by changes in the specific IGF binding
      proteins (IGFBPs). We have recently suggested that the bioavailability of
      circulating IGF-I is increased in the human fetus due to the molar excess of IGF
      I plus IGF-II relative to IGFBP-3 as well as the increased concentrations of
      IGFBP-2, which does not form a long-lived ternary complex. We have presently
      studied ternary complex formation between IGF, IGFBP-3, and acid labile subunit
      (ALS) to further assess if IGF-I bioavailability is increased in human fetal
      serum. In 19-35 week gestation fetal sera, a markedly decreased formation of the
      ternary complex was demonstrated by the general absence of IGFBP-3 (detected by
      Western immunoblotting) in the approximately 130-150 kDa ternary complex after
      neutral size chromatography. The predominant form of IGFBP-3 in fetal serum was a
      29 kDa fragment, which, following deglycosylation by Endoglycosidase-F, was
      demonstrated to consist of a approximately 20 kDa protein core. Despite the
      predominance of the 29 kDa IGFBP-3 fragment, we have previously demonstrated that
      the IGFBP-3 protease activity is not increased in fetal serum, in contrast to
      pregnancy or non-insulin dependent diabetes mellitus (NIDDM) sera.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7524887
TI  - Hematopoietic progenitors and synergism of interferon-gamma and stem cell factor.
AB  - Interferon-gamma (IFN-gamma), an immunoregulatory cytokine produced by activated
      T cells and natural killer cells in response to viral infection or other stimuli,
      is generally recognized as a suppressor of hematopoiesis. IFN-gamma inhibited in
      vitro colony formation by granulocyte-macrophage (GM), erythroid and
      multipotential progenitors. This cytokine exerted direct suppression on the
      proliferation process, but not on the commitment, of GM progenitors. The
      antiproliferative effects of IFN-gamma may, in part, result from the prolongation
      of the doubling time of GM progenitors. Clinically, IFN-gamma may play an
      important role in the pathogenesis of pancytopenia in aplastic anemia and in the
      hemophagocytic syndrome. However, as well as showing inhibitory effects, IFN
      gamma increased the number of pure and mixed megakaryocyte colonies formed by
      post-5-fluorouracil treated bone marrow cells and, moreover, the addition of IFN
      gamma to culture containing stem cell factor resulted in a synergistic effect on
      the development of both primitive hematopoietic progenitors and mature
      populations. These findings suggest that IFN-gamma has bifunctional activity in
      hematopoiesis.

PMID- 7524888
TI  - High dose busulphan/cyclophosphamide for autologous bone marrow transplantation
      is associated with minimal non-hemopoietic toxicity.
AB  - We retrospectively reviewed the regimen-related toxicity associated with
      busulphan (1 mg/kg orally QID days -7 to -4) and cyclophosphamide (60 mg/kg IV
      days -3 and -2) (Bu/Cy) chemotherapy in 69 consecutive patients who underwent
      autologous bone marrow transplantation (ABMT). Twenty-four patients received bone
      marrow (BM) alone, 22 received BM plus post-transplant granulocyte-colony
      stimulating factor (G-CSF) and 23 received peripheral blood progenitor cells
      (PBPC) +/- BM plus post-transplant G-CSF. Toxicity was scored using the criteria
      of Bearman. Grade II and III toxicities included mucosa (38%), liver (8%),
      central nervous system (5%), kidney (5%), heart (3%), pericardium (2%), bladder
      (2%) and lung (2%). There were five treatment related deaths (7%) from
      pneumonitis (2) and veno-occlusive disease, pulmonary hemorrhage and sepsis (1
      each). Post-transplant G-CSF (+/- PBPC) resulted in a trend (p = 0.07) towards a
      reduction in post-transplant stomatitis, but did not impact on the already low
      incidence of other organ toxicities. As Bu/Cy for ABMT is associated with minimal
      non-hemopoietic toxicity, the addition of other cytotoxic agents is justified in
      an attempt to augment the anti-tumour effect of this conditioning regimen.

PMID- 7524889
TI  - Trilineage response to rhG-CSF with subsequent clonal hematopoiesis in a patient
      with severe bone marrow aplasia.
AB  - We treated a patient with severe aplastic anemia with long-term administration of
      recombinant human granulocyte-colony stimulating factor (rhG-CSF). When a
      trilineage response of hematopoiesis was obtained after the first treatment, a
      chromosomal change [45XX, -7] was observed in 20 of the 20 metaphases examined.
      Later, we were able to show a monoclonal X inactivation pattern in the
      phosphoglycerate kinase (PGK) gene in the peripheral blood polymorphonuclear
      leukocytes and mononuclear cells, indicating the presence of clonal hematopoiesis
      regardless of the disappearance of the karyotype abnormality. We suggest that it
      is important to pay close attention to the appearance of clonal hematopoiesis
      during the administration of G-CSF to patients with idiopathic severe bone marrow
      aplasia.

PMID- 7524890
TI  - Developmental disabilities--a case for early intervention.

PMID- 7524892
TI  - Platelet support and the use of cytokines.
AB  - Severe thrombocytopenia and clinical bleeding remain major clinical problems in
      leukemic patients undergoing remission induction and those receiving high dose
      chemotherapy. Prophylactic platelet transfusions have made a major impact on
      hemorrhagic deaths over the last 20 years. The effectiveness of platelet
      transfusions is influenced by a number of clinical factors including the status
      of the spleen, prior bone marrow transplantation, the presence of disseminated
      intravascular coagulation and the presence of HLA antibodies. Optimal platelet
      transfusion therapy requires that transfusions be monitored routinely by post
      transfusion counts and that a refractory group be clearly defined. The cytokine
      granulocyte colony stimulating factor (G-CSF) has not had a clinically
      significant impact on thrombocytopenia. Granulocyte-macrophage colony stimulating
      factor (GM-CSF) also probably has little clinical relevance, although in a
      randomized study, thrombocytopenia was worse in GM-CSF-treated patients.
      Interleukin-3 (IL-3) can increase platelet count and has the potential to protect
      against thrombocytopenia in patients receiving chemotherapy. This hypothesis is
      currently being tested in on-going clinical trials.

PMID- 7524891
TI  - Bioactive Arg-Gly-Asp conformations in anti-integrin GPIIb-IIIa antibodies.
AB  - Antibodies can mimic the biological function of physiological ligands, yet few
      examples indicate the structural similarity between antibodies and the ligands
      that they mimic. Originally, the competition of antibodies for ligand binding
      sites was conjectured to be through similar three-dimensional conformations,
      which represent the "internal image" of the given ligand. Here we show that
      residues in a complementary determining region (CDR) can adopt the same bioactive
      structures observed in ligands. Structure-function studies of three anti-GPIIb
      IIIa murine monoclonal antibodies, PAC-1, LJ-CP3, and OP-G2, indicate that the
      RYD sequence in their H-CDR3 domain occupies the same conformational space as RGD
      in conformationally constrained, bioactive, GPIIb-IIIa cell-surface adhesion
      ligands. The relative location of the guanidinium and carboxylate groups in the
      RXD regions is identified as an important recognition feature, and the
      conformational space occupied by this region in the antibodies is only slightly
      larger than that in the most bioactive peptides. Additionally, we show that
      antibodies can unveil other potential bioactive sequences, which may impart
      specificity. Thus antibodies are an exquisite probe for identifying motifs of
      short adhesion stretches, thereby revealing amino acid sequences and restricted
      geometries that might be used as lead compounds in drug design.

PMID- 7524893
TI  - Expression of the c-kit ligand and interleukin 6 genes in mouse bone marrow
      stromal cell lines.
AB  - The expression of c-kit ligand and interleukin 6 (IL-6) genes in mouse bone
      marrow-derived stromal cell lines was examined using quantitative polymerase
      chain reaction (PCR) analysis based on the design of an internal DNA control. The
      stromal cells studied included the 14F1.1 endothelial-adipocytes that support
      long-term hemopoiesis and two additional cell lines (MBA-1, MBA-13) which do not
      have this function. All the cell lines expressed c-kit ligand gene
      constitutively, and this expression was not increased by lectins. On the other
      hand, the expression of the IL-6 gene was markedly induced in all the lines by
      lipopolysaccharide (LPS) and by phorbol 12-myristate 13 acetate (PMA). The
      constitutive expression of c-kit ligand in 14F1.1 cells was the lowest among the
      three cell lines studied and could be increased by stimulation with IL-4. Thus,
      we observed some quantitative differences among the cell lines in their
      expression of cytokine genes. However, the unique capacity of 14F1.1 cells to
      support in vitro hemopoiesis cannot thus far be explained solely on the basis of
      the ability of these cells to secrete cytokines which are not produced by other
      stromal cell lines. c-kit ligand may be necessary, but its presence alone is not
      sufficient for 14F1.1 cells to support prolonged hemopoiesis.

PMID- 7524895
TI  - Stem cell factor enhances the survival of irradiated human bone marrow maintained
      in SCID mice.
AB  - The effect of recombinant human stem cell factor (SCF) on the response of human
      fetal bone marrow progenitor cells to irradiation was studied using
      immunodeficient mice with human fetal bone grafts (SCID/Hu mice). SCID/Hu mice
      were treated with three intraperitoneal injections of 500 micrograms/kg SCF at 20
      h before, two h before, and four h after 100 cGy total body irradiation. Fourteen
      days following irradiation, the fetal bone grafts were harvested and studied.
      Most of the isolated bone marrow cells were human, as determined by flow
      cytometry. Colony forming assays were performed on the bone marrow to determine
      the survival of erythroid (BFU-E) and myeloid (CFU-GM) precursor cells. A
      statistically significant increase in BFU-E and CFU-GM survival after irradiation
      was observed for bone marrow maintained in the SCF treated mice when compared to
      bone marrow from mice not treated with SCF. The enhancement in colony forming
      unit survival after irradiation ranged from 4.3-fold for BFU-E (p = 0.05) to 13.1
      fold for CFU-GM (p = 0.002). These findings suggest that SCF may be of potential
      clinical value for the prevention of radiation-induced myelosuppression.

PMID- 7524896
TI  - [Ligation of RNA fragments in the presence of a complementary deoxyribonucleotide
      "substrate"].

PMID- 7524894
TI  - Production of human granulocyte colony stimulating factor by various kinds of
      stromal cells in vitro detected by enzyme immunoassay and in situ hybridization.
AB  - Production of human granulocyte colony stimulating factor (G-CSF) by stromal
      cells was studied in vitro. Induction of G-CSF by interleukin 1 (IL-1) and
      lipopolysaccharide (LPS) was compared using enzyme immunoassay in various kinds
      of stromal cells. Primary human bone marrow stromal cells, a human bone marrow
      derived stromal cell line (KM-102), and peripheral blood monocytes secreted small
      amounts of G-CSF without stimulation, while vascular endothelial cells and skin
      fibroblasts secreted G-CSF only when induced by IL-1 or LPS. The production of G
      CSF by monocytes was stimulated predominantly by LPS, whereas that by KM-102
      cells, endothelial cells, and fibroblasts was induced by IL-1 but much less so by
      LPS. IL-1 and LPS stimulated similar levels of G-CSF production by primary bone
      marrow stromal cells which consisted of various types of cells. In situ
      hybridization for G-CSF mRNA showed that only a small proportion of primary bone
      marrow stromal cells expressed a large amount of G-CSF mRNA upon stimulation. The
      positive cells were round or oval in shape, while most of the spindle-shaped
      stromal cells were negative for specific grains. Although further
      characterization of positive cells is needed, the results suggest that bone
      marrow stromal cells are heterogeneous in terms of their capacity for G-CSF
      production.

PMID- 7524897
TI  - [Immunohistochemical study of GABa- and substance P-immunoreactive structures in
      cat stellate ganglia].

PMID- 7524898
TI  - An insoluble aggregate of commercially available bovine serum albumin shows
      antiproteolytic activity.
AB  - Chemical aggregation of bovine serum albumin by extensive chemical crosslinking
      with glutaraldehyde yielded an insoluble protein preparation with significant
      antiproteolytic activity. This was presumably due to the presence of alpha 2
      macroglobulin in bovine serum albumin preparations. Chemical crosslinking of
      bovine serum albumin under optimum conditions was found to increase its
      antitryptic activity by about four times. The results indicate that enhanced
      rigidity of alpha 2-macroglobulin structure increases its antitryptic activity.

PMID- 7524899
TI  - Glycolipids noncovalently bound to DEAE-Sephadex. Use of the complexes for
      purification of IgM and IgG anti-(Gal beta 1-->3 GalNAc-) antibodies.
AB  - A method for the purification by affinity of antibodies of the IgM and IgG
      classes against the (Gal beta 1-->3 GalNAc-) epitope has been developed. The
      immunoadsorbent is based on the property of DEAE-Sephadex to bind acid
      glycolipids bearing this epitope, by electrostatic and hydrophobic interactions
      in a stable form in an aqueous medium. The acid glycolipid employed was asialo
      GM1 ganglioside (GA1) derivatized to produce a carboxyl function on the olefinic
      bond of the sphingosine moiety (GA1 acid). The DEAE-Sephadex-GA1 acid complex was
      used to purify the antibodies of the IgG class from serum of an immunized rabbit
      and of the IgM class from a human serum. The specific activities of the purified
      antibodies were 1,200- to 2,400-fold higher, and the antibody activities were
      quantitatively recovered respect to the untreated sera, in both cases. The
      sequential use of two immunoadsorbents: DEAE-Sephadex-ganglioside and DEAE
      Sephadex-GA1 acid, allows the separation of the two classes of immunoglobulins
      that recognize the same sugar residues in glycolipids.

PMID- 7524901
TI  - Gliotoxin induces apoptosis in mouse L929 fibroblast cells.
AB  - The effect of the fungal toxin gliotoxin on the adherence and viability of mouse
      L929 cultured cells was examined. Gliotoxin at concentrations below 2 microM had
      no effect on cell function. The initial effect of exposure (6 h) resulted in the
      loss of cell adherence, with the non-adhered cells retaining viability. However,
      prolonged exposure (24 h) did not significantly enhance gliotoxin's effect on
      cell adherence, though the majority of non-adhered cells were found to have died
      by apoptosis, as confirmed from (i) electron microscopic examination and (ii)
      agarose gel electrophoresis of isolated DNA. The addition of foetal bovine serum
      to the culture medium had no effect on gliotoxin's activity. Ethanol (gliotoxin's
      solvent) had no effect on the assayed cell functions suggesting that the observed
      effects are due to gliotoxin alone. These results demonstrate for the first time
      that gliotoxin can cause apoptosis in cells of non-haematopoietic origins.

PMID- 7524900
TI  - Location and nature of carbohydrate groups in proform of human major basic
      protein isolated from pregnancy serum.
AB  - From human pregnancy serum we have isolated the proform of eosinophil major basic
      protein (proMBP), which forms a complex with pregnancy-associated plasma protein
      A (PAPP-A), PAPP-A/proMBP. It is shown that proMBP contains O-linked glycan bound
      to Ser-24, Thr-25 (fully substituted), and to Thr-23 and Thr-34 (partially
      substituted). N-linked glycan is bound to Asn-86 and O-linked glycosaminoglycan
      is bound to Ser-62 (both fully substituted). From the RP-HPLC elution profile and
      mass spectra of tryptic peptides it is found that proMBP is extremely
      heterogeneous with respect to glycosylation.

PMID- 7524903
TI  - Expression of human prostatic acid phosphatase and prostate specific antigen
      genes in neoplastic and benign tissues.
AB  - Expression of human prostatic acid phosphatase (ACPP) and prostate specific
      antigen (PSA) genes in prostatic carcinoma (CAP) and benign prostatic hyperplasia
      (BPH) was investigated by northern blot analyses. The expressions of ACPP and
      PSA, as well as the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) and lactate dehydrogenase-muscle (LDH-A), were elevated significantly in
      prostatic carcinoma when compared with the expressions of these genes in benign
      prostatic hyperplasia in the same patient. The expression of the actin gene in
      both neoplastic and benign hyperplasia remained the same.

PMID- 7524902
TI  - Detection of conformational changes in rat kidney gamma-glutamyl transpeptidase
      by an antibody against a synthetic peptide belonging to part of the reactive
      centre of the enzyme.
AB  - Polyclonal antibodies were produced against rat kidney gamma-glutamyl
      transpeptidase (GGT) and against a synthetic peptide corresponding to residues
      512-534 in rat GGT. The anti-peptide antibody bound denatured GGT, acivicin
      treated GGT and GGT absorbed to microtiter plates, but not GGT in solution, and
      did not inhibit GGT. The antibody against native GGT inhibited its activity in
      solution and did not bind efficiently adsorbed GGT in direct ELISA. It was active
      in direct and competition ELISA using kidney brush border membranes as the
      adsorbed antigen. The results indicate that these antibodies recognize
      conformational rather than sequence epitopes in GGT, and that marked changes
      occur in the conformation of GGT upon its absorption to plates or its reaction
      with acivicin.

PMID- 7524906
TI  - Myeloma cell contamination of peripheral blood stem cell grafts in patients with
      multiple myeloma treated by high-dose therapy.
AB  - In order to assess the contamination with malignant cells of peripheral blood
      stem cell (PBSC) transplants used to support high-dose therapy in multiple
      myeloma (MM), we used the immunoglobulin heavy chain gene radioactive
      fingerprinting polymerase chain reaction (PCR) method to detect clonal cells in
      PBSC from 10 patients. The sensitivity of the technique allowed the detection of
      one clonal cell among 10(4) normal blood mononuclear cells. A clonal band was
      detected in 4 of 11 leukaphereses samples. The level of contamination was low
      because a clonal band could never be identified on ethidium bromide-stained
      agarose gels whose sensitivity is between 1 and 5%. The use of granulocyte-colony
      stimulatory factor (G-CSF) in combination with chemotherapy in three cases did
      not seem to increase the contamination of PBSC grafts; in one patient, G-CSF was
      used during a second course of leukapheresis which was free of detectable clonal
      cells whereas the first one performed after chemotherapy alone contained clonal
      cells. Thus, PBSC grafts may rarely be completely devoid of clonal potentially
      malignant cells but the level of contamination is much lower than in BM grafts.
      Whether graft contamination is an important adverse prognostic factor for
      patients with MM undergoing intensive treatment and autografting is still
      unsettled.

PMID- 7524904
TI  - Phase II study of autologous filgrastim (G-CSF)-mobilized peripheral blood
      progenitor cells to restore hemopoiesis after high-dose chemotherapy for lymphoid
      malignancies.
AB  - The hemopoietic growth factor filgrastim (r-metHu G-CSF) stimulates
      granulopoiesis after autologous BMT and can also be used as a peripheral blood
      progenitor cell (PBPC)-mobilizing agent. Rapid platelet recovery follows the
      addition of filgrastim-mobilized PBPC to autologous BMT. We have now studied 29
      adults with malignant lymphoma, Hodgkin's disease or ALL to assess the ability of
      filgrastim-mobilized PBPC to rapidly and durably restore hemopoiesis without bone
      marrow (BM) infusion. Patients with a high yield of PBPC from three
      leukaphereses, defined as > 30 x 10(4)/kg GM-CFC, were eligible for PBPC
      transplant without BM. Patients with a low yield of GM-CFC received both PBPC and
      BM infusion. After filgrastim therapy 12 or 24 micrograms/kg/day by continuous sc
      infusion for 6 or 7 days, a high yield was obtained in 11 of 29 patients.
      Kinetics of recovery of both the platelet and neutrophil counts were more rapid
      in the high yield group than in the low yield group. The platelet count recovered
      to > 20 x 10(9)/l at a median of 9 days, to > 50 x 10(9)/l at 11 days and the
      neutrophil count to > 0.5 x 10(9)/l at 9 days in the high yield group compared
      with 12 days, 37 days and 10 days, respectively, in the low yield group (p =
      0.028, p < 0.001 and p = 0.027). Fewer platelet transfusions were required in the
      high yield group (median 11 vs 29.5 units, p = 0.021).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7524907
TI  - Comparison of autografting using mobilized peripheral blood stem cells with and
      without granulocyte colony-stimulating factor in malignant lymphomas.
AB  - Peripheral blood is becoming widely used as the only source of hematopoietic stem
      cells to support marrow ablative therapy in advanced lymphoma. We report data
      from 23 patients with high risk non-Hodgkin's (n = 19) and Hodgkin's lymphoma (n
      = 4) who underwent high-dose therapy with mobilized peripheral blood stem cell
      (PBSC) autografting. Peripheral blood progenitors were recruited using cytotoxic
      chemotherapy followed by administration of recombinant human G-CSF (filgrastim 5
      micrograms/kg/day). Myeloablative treatment with autologous PBSC support was
      administrated to the 23 patients and followed by G-CSF at the same dose after
      cell reinjection. Hematopoietic reconstitution was compared with a control group
      of lymphoma patients who received chemotherapy mobilized PBSC transplantation but
      without G-CSF prior to leukaphereses or after high-dose therapy. The median time
      to neutrophil recovery > 0.5 x 10(9)/l was significantly shorter in study
      patients compared with the control patients (10 days and 17 days respectively) (p
      < 0.05). Self sustaining platelet counts of > 50 x 10(9)/l occurred at a median
      time of 17 days in both groups. Stable hemopoietic reconstitution was seen with a
      follow-up of 6 months after PBSC transplantation. In addition, a significant
      relationship was observed between the number of CFU-GM infused and the time to
      platelet recovery. We confirm the effectiveness of G-CSF given prior to PBSC
      harvesting in generating high numbers of progenitor cells. Hematologic recovery
      following high-dose therapy was improved after PBSC rescue and G-CSF.

PMID- 7524905
TI  - In vitro and in vivo effects of recombinant human erythropoietin plus recombinant
      human G-CSF on human haemopoietic progenitor cells.
AB  - We tested in vitro the effect of recombinant human erythropoietin (rhEPO) plus
      recombinant human G-CSF (rhG-CSF) on purified human CD34+ haemopoietic
      progenitors (HP) and in vivo in patients who had undergone anti-cancer
      chemotherapy for advanced ovarian cancer. In this preliminary experience we found
      that, in vitro, rhEPO potentiates the effect of rhG-CSF on HP growth and
      differentiation toward the granulocyte-macrophage lineage. rhEPO plus rhG-CSF
      produced in vitro a proliferative stimulus of HP which represents 26% of the
      maximum stimulation obtained using IL-1, IL-3, IL-6, G-CSF, GM-CSF and stem cell
      factor in combination. In the patients treated with rhEPO plus rhG-CSF after
      chemotherapy, we observed a favourable trend for platelet and neutrophil
      recoveries compared with a control group treated with rhG-CSF alone and a
      significantly higher haematocrit nadir was observed in the rhEPO plus rhG-CSF
      series. In the patients treated with rhEPO plus rhG-CSF we observed a significant
      increase of circulating colony-forming unit granulocyte-macrophage (CFU-GM) and
      burst forming unit-erythroid (BFU-e) compared with the rhG-CSF series. Our
      results, in vitro and in vivo, encourage the in vivo use of rhEPO plus rhG-CSF to
      improve blood cell recoveries of patients who have undergone conventional or high
      dose chemotherapy. Moreover, rhEPO plus rhG-CSF was demonstrated to be a good HP
      mobilising treatment for blood stem cell collection after chemotherapy.

PMID- 7524908
TI  - Antibodies to hepatitis C virus in human immunoglobulins: clinical meaning and
      diagnostic difficulties in children undergoing bone marrow transplant.
AB  - Anti-HCV antibodies were detected in 11 children undergoing BMT. All of them had
      received intravenous immunoglobulins (Ig) at a dose of 500 mg/kg every 2 weeks
      for the first 100 days post-BMT. Antibody titers appeared after the first dose
      and became undetectable between 1 and 6 months after the last dose of Ig.
      Detection of anti-HCV antibodies in these multitransfused patients raised doubts
      about their clinical significance. The clearance of antibody titers in the
      ensuing months, negativity of HCV RNA in the serum of the patients and the
      presence of anti-HCV in some batches of the commercial preparations administered
      supported the diagnosis of a passive transfer of antibodies and that true HCV
      infection could be ruled out. Routine screening of donors with the most sensitive
      tests and exclusion of anti-HCV positive sera from plasma pools should be
      mandatory. The presence of anti-HCV in these products has important clinical
      implications, leading to more expensive and time-consuming diagnostic procedures.

PMID- 7524909
TI  - A novel cystic fibrosis mutation, Y109C, in the first transmembrane domain of
      CFTR.

PMID- 7524910
TI  - Two novel rare frameshift mutations (2423 del G in exon 13 and 1215 del G in exon
      7) and one novel rare sequence variation (3271 + 18 C or T) identified in a
      patient with cystic fibrosis.

PMID- 7524911
TI  - Polymorphisms in the keratin 8 gene detected by PCR.

PMID- 7524914
TI  - Nonisotopic detection of mutations using a modified single-strand conformation
      polymorphism analysis.
AB  - This report describes a rapid convenient screening system with improved
      sensitivity to detect mutations in the cystic fibrosis transmembrane regulator
      (CFTR) gene based on nonisotopic SSCP analysis. Because conventional SSCP
      analysis is often hampered by poor yield of single-stranded DNA, we applied the
      well-established solid-phase technique in which streptavidin-coated magnetic
      beads are used to immobilize biotinylated polymerase chain reaction (PCR)
      products. High yield of single-stranded DNA can be eluted from the solid phase by
      denaturation and used for SSCP analysis. An additional advantage of this
      procedure is that the immobilized single strand is available without any further
      purification steps for solid-phase sequencing.

PMID- 7524912
TI  - A mouse Y chromosome gene encoded by a region essential for spermatogenesis and
      expression of male-specific minor histocompatibility antigens.
AB  - A new mouse Y chromosome gene, Smcy, has been isolated from the region encoding
      Spy, a spermatogenesis gene and Hya and Sdma, the genes that, respectively,
      control the expression of the male specific minor histocompatibility antigen H-Y,
      as measured by specific T-cell assays and the serologically detected male antigen
      SDMA. Smcy is well conserved on the Y in mouse, man and even marsupials. It is
      expressed in all adult male tissues tested and can also be detected during mouse
      development from as early as two cells. In addition, its human Y homologue, SMCY,
      is expressed in multiple tissues and maps to the same Yq deletion interval as the
      human H-Y antigen controlling locus, HY.

PMID- 7524916
TI  - Ejaculatory dysfunction after transurethral microwave thermotherapy for treatment
      of benign prostatic hyperplasia.
AB  - The possibility of retrograde ejaculation or impotence after transurethral
      resection of the prostate has led to searches for other treatments for benign
      hyperplasia (BPH). Transurethral microwave thermotherapy (TUMT) was administered
      to 100 men with a mean age of 61 years and moderate to severe BPH in one 60
      minute outpatient session without anesthesia. A urethral catheter was frequently
      maintained for 5 to 7 days to avoid urinary complaints. Of the 100 original
      patients, 79 were followed from 3 to 24 months (mean 7.3 months). The prostate
      volume, irritative and obstructive symptoms, residual urine volume, and urinary
      flow improved (P < 0.01). No systemic complications were encountered. There were
      minor complications such as epididymitis, urethral bleeding, and severe
      micturition discomfort within the first 30 days postoperatively. A total of 7
      ejaculatory disorders occurred among 64 patients (11%), 6 complete absences and 1
      retrograde ejaculation without recovery for more than 6 months. As TUMT is a
      fairly new method, further studies must be done to define its effectiveness and
      safety.

PMID- 7524913
TI  - Identification of two new mutations (711 +3A-->G and V1397E) in CF chromosomes of
      Albanian and Macedonian origin.

PMID- 7524917
TI  - Randomized comparison of balloon dilation and transurethral incision for
      treatment of symptomatic benign prostatic hyperplasia.
AB  - The concept of relieving the symptoms of benign prostatic hyperplasia (BPH) by
      dilating the urethral has existed for centuries. Thirty patients with a
      clinically estimated prostate gland size of 25 g or less were randomized to
      either balloon dilation (BDP) or transurethral incision of the prostate (TUIP).
      The mean pretreatment Madsen-Iverson symptom scores in the two groups were 15.0
      +/- 4.9 (SD) and 15.4 +/- 4.4, respectively. The early response rates were 87% fo
      BDP and 86% for TUIP, with the mean symptom scores declining to 3.4 +/- 2.8 after
      dilation and 4.2 +/- 6.6 after incision. Among the 14 patients who initially
      responded to BDP, 2 have been lost to follow-up, 1 died of unrelated causes at 17
      months with no urinary symptoms, 2 remain in response at 32 and 38 months, and
      the other 9 (75% of those available for evaluation) have developed recurrences.
      Among the 12 patents who responded to TUIP, 2 have been lost to follow-up, 8
      remain in response at 14 to 48 months, and 2 (20%) developed recurrences by 44
      months of follow-up. In the short term, both BDP and TUIP are effective for
      treating bladder outlet obstruction in men with relatively small prostates.
      However, the effect of dilation appears to be less durable than that of incision.

PMID- 7524915
TI  - A 32-bp deletion (2991del32) in the cystic fibrosis gene associated with CFTR
      mRNA reduction.
AB  - Cystic fibrosis, a common recessive disorder of exocrine glands, is caused by
      mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
      We describe the identification of a 32-bp deletion within the coding region of
      CFTR that involves the nucleotides 2991-3022 in exon 15 (2991del32). This unusual
      frameshift mutation was confirmed in three unrelated German families, accounting
      for a frequency of 0.3% in 1,028 CF chromosomes. All identified patients are
      compound heterozygotes for 2991del32 and for the most frequent cystic fibrosis
      mutation, delta F508. The evaluation of clinical data revealed typical symptoms
      of cystic fibrosis, including pancreatic insufficiency, in all three index cases.
      To characterize further the mutation in the CFTR transcript, we analysed RNA from
      lymphocytes by reverse transcription and PCR amplification. 2991del32 transcripts
      were detectable neither in the RNA sample from a patient compound heterozygous
      delta F508/2991del32 nor in the parental sample heterozygous wild-type/2991del32.
      These data indicate that the 32-bp deletion causes a pancreas insufficient cystic
      fibrosis phenotype by a severe reduction of CFTR mRNA.

PMID- 7524918
TI  - Conjugates or dsDNA linked to human gammaglobulin inhibit anti-dsDNA antibodies
      in vitro.
AB  - Previous studies have shown that both nucleosides and oligonucleotides linked to
      isologous gammaglobulin suppress anti-nucleic acid antibody production both in
      vivo and in vitro. The aim of this study was to determine whether one can make a
      DNA-human gammaglobulin (HGG) conjugate which can inhibit anti-double stranded
      DNA (dsDNA) antibodies obtained from a heterogeneous population of systemic lupus
      erythematosus (SLE) sera. To do so, we constructed conjugates of sonicated dsDNA
      fragments of 100-400 base pairs covalently linked to HGG with varying degrees of
      substitution of DNA:HGG. An ELISA inhibition assay was used to determine which
      conjugate best inhibits the binding of anti-dsDNA antibodies. Conjugate 2,
      prepared with monomeric HGG (150 kD) with a high degree of substitution (3.72
      DNA:HGG) inhibited the binding of anti-dsDNA antibodies from 27 of 31 SLE sera.
      In addition, this conjugate inhibited the spontaneous formation of anti-dsDNA in
      vitro by cultured lymphoid cells from selected SLE patients. Together, this data
      suggests that a 'generic' tolerogen may provide an antigen specific therapy for
      SLE.

PMID- 7524919
TI  - Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of
      Siemens.
AB  - Ichthyosis bullosa of Siemens (IBS) is an autosomal dominant skin disorder that
      resembles epidermolytic hyperkeratosis (EHK). We have identified mutations in two
      families originally diagnosed with EHK and in four families diagnosed with IBS at
      the same codon in the highly conserved carboxy terminal of the rod domain of
      keratin 2e, thus revealing a mutational hot spot. Our results allow a
      differential diagnosis to be made between IBS and EHK at the genetic level and we
      suggest that patients diagnosed with EHK, but lacking keratin K1 or K10
      mutations, should be re-examined for mutations in their K2e genes.

PMID- 7524920
TI  - Evolution and controversies in the management of low-stage nonseminomatous germ
      cell tumors of the testis.
AB  - The results of changing treatment modalities in 690 consecutive patients with low
      stages nonseminomatous germ-cell tumors (NSGCT) of the testis were analyzed.
      Overall, 120 patients (17.4%) suffered relapses, and 25 (3.6%) died of cancer
      after a follow-up period ranging from 2 to 20 years. The indications for primary
      (nerve-sparing) retroperitoneal lymph-node dissection (RPLND) were gradually
      restricted from clinical stages I, IIA, and IIB to stages I and IIA with normal
      postorchiectomy markers only, but we recognize that the management of clinical
      stage I NSGCT of the testis remains controversial. All other patients may be
      treated with primary chemotherapy followed by nerve-sparing RPLND for any
      residual mass. Adjuvant chemotherapy is mandatory in pathological stage IIC
      disease, but this pathological category will disappear with adoption of the
      restrictions for primary nerve-sparing RPLND, and two courses of adjuvant
      chemotherapy are adequate treatment for patients with pathological stages IIA and
      IIB disease, who cannot be carefully followed.

PMID- 7524921
TI  - Stage II nonseminomatous germ-cell testicular tumors--the Indiana experience and
      risk-benefit analysis.
AB  - Controversy exists in the appropriate management of patients with nonseminomatous
      testicular cancer presenting as clinical stage B disease. Traditional treatment
      in the United States has included retroperitoneal lymph-node dissection (RPLND).
      Conversely, in Europe and other places some of these patients have been managed
      with primary chemotherapy. The experience with RPLND in clinical stage B disease
      at Indiana University from 1965 to 1989 was reviewed. A total of 174 patients
      were considered to be in clinical stage B prior to RPLND. After RPLND, 23% of
      these patients (n = 41) were found to have pathological stage A disease. In all,
      77% (n = 133) were determined to be in pathological stage B. Of those
      pathological stage B patients who did not receive adjuvant chemotherapy, 65% were
      cured by RPLND alone. The pathological stage B patients who went on the receive
      postoperative adjuvant chemotherapy displayed an overall 14% chance of relapse.
      (Patients treated early in the series did not receive cisplatin-based
      chemotherapy.) The overall survival over the entire period was 96%. In the more
      modern era, during which cisplatin-based chemotherapy was available, the overall
      survival was 98%. RPLND is an effective procedure for the management of clinical
      stage B nonseminomatous testicular cancer. It provides excellent survival in
      patients found to have pathological stage B disease; additionally, it avoids the
      unnecessary toxicity of chemotherapy in the 23% of patients who in fact are in
      pathological stage A.

PMID- 7524923
TI  - Histochemical and ultrastructural investigation of heterogeneous Purkinje neurons
      in mammalian cerebellum.
AB  - The cerebellum of rat, rabbit, mouse, and bat were studied after staining with
      the Hematoxylin-Basic Fuchsin-Picric acid (HBFP) technique. In each species,
      heterogeneous Purkinje neurons became evident on the basis of red (i.e.,
      fuchsinorrhagic) and blue (i.e., HBFP-negative) staining of cells. The former
      ranged from normal to atrophic-looking cells, while the blue staining Purkinje
      cells always showed typical perikaryal morphology with normal vesicular nucleus
      and prominent nucleolus. Staining differences were also seen by several different
      stains; however, the HBFP technique proved superior in the characterization of
      Purkinje cell heterogeneity owing to the tinctorial differences. The two classes
      of Purkinje neurons were still present after perfusion fixation. Electron
      microscopy demonstrated variable electron density in the Purkinje cells.
      Fuchsinorrhagic Purkinje neurons were absent in the 1-week old rats, but their
      number increased gradually thereafter. Tissue sections pretreated with RNase,
      DNase, or protease demonstrated that the fuchsinorrhagia of Purkinje neurons is a
      function of DNA/acidic protein complex. Since nucleic acids do not increase in
      Purkinje cells after maturation (i.e., after 8 weeks postnatal), the nucleic
      acids-associated-proteins, that are known to play a role in the regulation of
      gene expression, may be responsible for the fuchsinorrhagia of these Purkinje
      neurons.

PMID- 7524924
TI  - Characterization of insulin-like growth factor II (IGF-II) and IGF binding
      proteins in patients with non-islet-cell tumor hypoglycemia.
AB  - Insulin-like growth factor II (IGF-II) in serum and tumor extracts from five
      patients with non-islet-cell tumor hypoglycemia (NICTH) has been characterized.
      These tumors contained large quantities of IGF-II (2.4-14.2 micrograms/g
      tissues). The serum IGF-II levels in four of five patients were a little high and
      the serum IGF-I levels in five patients were low. The serum IGF-II/IGF-I ratios
      in these patients ranged from 24.1 to 64.2, and the values were significantly
      greater than those in normal subjects (1.7-7.1). When the sera were gel-filtered
      on a Sephacryl S-200 column under neutral conditions, the proportion of the free
      form of IGF-II was not increased. However, in four of five patients, an abnormal
      IGF-II-IGF binding protein complex was found. When serum IGF binding proteins
      (IGFBPs) were analyzed by Western ligand blotting, serum IGFBP-2 increased in
      these patients. When the tumor extracts and sera were gel-filtered on a Biogel P
      60 column under acidic conditions, the majority of IGF-II in these sera was a big
      form of IGF-II. As compared to authentic IGF-II, insulin receptor reactivities
      and IGF-II receptor reactivities of tumor extracted IGF-II increased in two of
      three patients. These data indicate that in patients with NICTH, heterogenous IGF
      II is produced in respect of size and bioactivities, and that the characteristics
      of IGF binding protein are altered. Thus, to find IGF-II producing tumors among
      extrapancreatic tumors associated with hypoglycemia, the quality of IGF-II as
      well as the quantity should be studied.

PMID- 7524926
TI  - Development of hypothyroidism with thyroid stimulation blocking antibody long
      after treatment with antithyroid drugs in a patient with hyperthyroid Graves'
      disease: a case report.
AB  - We observed a patient manifesting spontaneous hypothyroidism with thyroid
      stimulation blocking antibody (TSBAb) long after treatment with antithyroid drugs
      (ATDs) for hyperthyroid Graves' disease. A 19-year-old female with Graves'
      disease was treated with ATDs for approximately 2 years; after cessation of ATDs,
      hyperthyroidism did not recur. Nine years later, she was again seen in our
      hospital because of symptoms indicative of hypothyroidism. Thyroid hormone
      replacement was commenced after laboratory confirmation of hypothyroidism. TSH
      binding inhibitor immunoglobulin and TSBAb were both positive, while thyroid
      stimulating antibody (TSAb) was negative, at the time of diagnosis of
      hypothyroidism. These results indicated that the alterations in thyroid function
      in this patient appeared to relate to the presumed decline in the activity of
      TSAb and the appearance of TSBAb years after ATDs administration had been
      discontinued.

PMID- 7524925
TI  - Comparison between insulin-like growth factor-I (IGF-I) and IGF binding protein-3
      (IGFBP-3) measurement in the diagnosis of growth hormone deficiency.
AB  - To analyze the utility of insulin-like growth factor-I (IGF-I) and insulin-like
      growth factor binding protein-3 (IGFBP-3) radioimmunoassay in the diagnosis of
      growth hormone deficiency (GHD) we measured IGF-I and IGFBP-3 in sera from normal
      children (n = 309), short children (n = 99) and patients with GHD (n = 73). In
      80% and 93% of classical GHD (cGHD), IGF-I and IGFBP-3 levels, respectively, were
      below the age-related cutoff levels (lower limit). In 81% and 88% of normal short
      children (NS), IGF-I and IGFBP-3 levels, respectively, were above the age-related
      cutoff levels. Thus, both IGF-I and IGFBP-3 were good parameters for screening
      GHD. In contrast, in more than half of partial GHD (pGHD), either IGF-I or IGFBP
      3 was above the age-related cutoff levels. The poor discrimination between
      patients with pGHD and NS by using these two parameters may be the result of
      their relatively similar GH levels, as compared to cGHD, or due to the
      limitations of GH stimulation tests. In about 80-90% of NS, IGF-I and IGFBP-3
      were above the age-related cutoff levels at all ages. A hundred percent of cGHD
      under 10 years old had IGFBP-3 below the age-related cutoff levels, whereas 79%
      of cGHD under 10 years old had IGF-I below the age-related cutoff levels. Thus in
      the younger age groups, IGFBP-3 may be more sensitive than IGF-I. It may be
      because IGFBP-3 levels are relatively higher than those of IGF-I in younger
      subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524922
TI  - Human seminal plasma analysis of five tumor markers: CA 125, alpha-fetoprotein,
      CA 50, CA 19.9, and CA 195.
AB  - OBJECTIVE: To evaluate tumor markers in seminal plasma and their possible
      relationship with fertility. METHODS: Five different tumor markers (alpha
      fetoprotein, CA 125, CA 19.9, CA 50, and CA195) were studied in seminal plasma
      and serum from 42 males (14 volunteers from semen donation and 28 males from
      infertile couples). RESULTS: CA 50 and CA 19.9 levels were more than 300 times as
      high in seminal plasma as in serum (4,396.4 U/mL vs. 13.9 and 3,893.5 U/mL vs.
      11.5). CA 125 levels were 14 times as high in seminal fluid as in serum (217.2
      U/mL vs. 15.1), and CA 195 levels 22 times as high (122.5 U/mL vs. 5.6). alpha
      Fetoprotein levels in seminal plasma were one-third those in serum (0.75 ng/mL
      vs. 2.47). Seminal levels of CA 125, CA 50, and CA 19.9 were correlated with the
      duration of infertility. Compared with donors, among seminal fluids from
      infertile couples there was a trend to higher levels of CA 19.9 and CA 125. CA
      125 levels were lower in samples having normal sperm counts, and CA 125 and CA
      19.9 levels were lower among couples who conceived compared with those who did
      not conceive. Tumor markers, either in seminal plasma or in serum, were not found
      to be correlated with semen characteristics. CONCLUSIONS: It appears that seminal
      levels of the tumor markers studied depend on more factors than the single serum
      concentration. The biological significance of the high seminal levels of the four
      carbohydrate antigens, and the association of low levels of CA 125 and CA 19.9
      and fertility, could not be determined from our study. It is suggested, however,
      that CA 125 and CA 19.9 could be used as seminal plasma markers of fertility.

PMID- 7524927
TI  - Identification of galanin-immunoreactive cells in the anterior pituitary of male
      monkeys (Macaca fascicularis).
AB  - The localization of galanin (GAL) was studied in the anterior pituitary of adult
      male macaque monkeys immunohistochemically. GAL-immunoreactive fiber bundles were
      noted in the posterior lobe of the pituitary. Cells immunoreactive for GAL were
      observed in the anterior lobe, and colocalization studies revealed that GAL-like
      immunoreactivity was present in gonadotrophs and thyrotrophs. The differences
      among the monkey, human and rat in GAL-immunoreactive localization may indicate
      that the regulation of GAL in the three species differs.

PMID- 7524928
TI  - Compensatory adrenal growth and steroidogenesis after unilateral adrenalectomy.
AB  - To examine the effect of unilateral adrenalectomy on compensatory growth and
      steroidogenesis in the remaining adrenal gland, we determined the tissue
      concentrations of protein, DNA and corticosterone in the remaining adrenal gland
      and the circulating corticosterone and ACTH concentrations at 1, 3, 5, 7 and 14
      days after unilateral adrenalectomy in male rats. The remaining adrenal weight
      and total protein content increased steadily over the 14 days after the
      operation, while the plasma ACTH increased transiently on the 1st day. The
      adrenal total DNA level was not significantly changed after unilateral
      adrenalectomy, whereas the protein/DNA ratio was significantly increased by the
      14th day. These findings suggest that compensatory growth is not induced by an
      increase in ACTH and that hypertrophy may occur rather than hyperplasia in the
      remaining gland. The serum corticosterone levels and corticosterone concentration
      in the remaining gland were significantly increased by the 3rd day, when the
      plasma ACTH levels returned to normal. The aldosterone/corticosterone ratio in
      the remaining gland did not change during the experiment. These results indicate
      that steroidogenesis stimulating factors other than ACTH may be present and
      stimulate rather the early stages than the late stages of steroidogenesis under
      conditions of unilateral adrenalectomy.

PMID- 7524930
TI  - [High-dose progestational contraception: advantages].
AB  - In spite of the nearly total effectiveness of classic estrogen-progestogen oral
      contraception and its good overall tolerance, in a not inconsiderable number of
      situations yet, it is not possible to resort to it. These situations are the
      following: high blood pressure, hyperlipemia, diabetes, minor mastopathy,
      premenstrual tension either spontaneous or under estroprogestogen therapy.
      Macroprogestational contraception using either pregnanes (chlormadinone acetate)
      or nor-pregnanes, promegestone, nomegestrol acetate, can be then the right
      solution. Clinical and metabolic tolerance is excellent. In the occurrence of
      hypoestrogeny symptoms, a combination of nomegestrol acetate-estradiol 17 beta,
      transdermally administered, has given top results in a preliminary study.

PMID- 7524929
TI  - Recent progress in TSH receptor studies with a new concept of "autoimmune TSH
      receptor disease".
AB  - Recent progress in the studies of epitope analysis of the TSH-R against TSH-R Ab
      was reviewed extensively. Using both site-directed mutagenesis and synthetic TSH
      R peptide, binding and/or action sites of TSH-R Ab have been known to be multiple
      and discontinuous, but the significance of two unique and TSH-R specific regions
      has been implicated. Further, the possible existence of heterogeneity among
      stimulatory TSH-R Ab has also been indicated. As for immunogenetic factors
      related to autoimmune thyroid diseases, studies on HLA analysis, TSH-R specific T
      lymphocyte analysis and VH analysis of TSH-R Ab were discussed. Of note was the
      negative association of HLA-DP w2 antigen in Japanese patients with Graves'
      disease and hypothyroidism due to blocking TSH-R Ab, and we proposed a new
      concept of autoimmune TSH receptor disease within autoimmune thyroid disease and
      emphasized possible critical roles of HLA-DP. Recent evidence of restricted usage
      of the Ig VH gene in cloned B lymphocytes from Graves' patients producing TSH-R
      Ab has also been presented.

PMID- 7524931
TI  - [Evaluation of trisomy 21 risk by serial determination of chorionic gonadotrophin
      hormone and alpha-fetoprotein: results of a national pilot study].
AB  - Previous studies, as early as 1984, have demonstrated the efficiency of maternal
      serum markers to screen for Down syndrome. These markers were AFP, hCG, oestriol
      and beta-1-glycoprotein. A pilot study was initiated in France in 1990 to
      evaluate these markers. It lasted from May 1990 until April 1991. 22,410
      pregnancies were monitored in total, and 19,407 for women between 30 and 37 years
      of age. The pregnancy outcome was known for 20,151 cases (86.6%). Sensitivity and
      predictive value of the test was calculated on 17,362 dosages which outcome was
      known. The sensitivity based on hCG only was 59.4% (38/64) for trisomy 21 and
      positive predictive value 1.65% (38/2,307). This test is a better marker than
      maternal age. In the pilot study it induced a 13.2% rate of amniocentesis. If the
      risk was calculated using both hCG and AFP results, the performances of the test
      were better. At equal rate of amniocentesis, the double test increases the
      sensitivity (+9.5% at risk 1/200, +7% at risk 1/250, +14.4% at risk (1/350). The
      strategy of double dosages decreases the number of amniocentesis for a given
      sensitivity rate. This decrease is more spectacular for high levels of
      sensitivity. This pilot study confirms already published results. Maternal serum
      markers are the best tools, combined with maternal age to evaluate the risk of
      trisomy 21.

PMID- 7524932
TI  - Diphtheria in Ukraine.

PMID- 7524934
TI  - Plague in India.

PMID- 7524935
TI  - Plague in India: update.

PMID- 7524933
TI  - AIDS and HIV-1 infection in the United Kingdom: monthly report.

PMID- 7524936
TI  - Transmissible spongiform encephalopathies.

PMID- 7524937
TI  - Quantification of proteins on polyacrylamide gels (nonradioactive).

PMID- 7524939
TI  - The electrophoretic elution of proteins from polyacrylamide gels.

PMID- 7524938
TI  - Identification of glycoproteins on nitrocellulose membranes and gels.

PMID- 7524940
TI  - Nondenaturing polyacrylamide gel electrophoresis of proteins.

PMID- 7524941
TI  - Protein blotting.

PMID- 7524942
TI  - Detection of polypeptides on immunoblots using secondary antibodies or protein A.

PMID- 7524943
TI  - SDS polyacrylamide gel electrophoresis of proteins.

PMID- 7524944
TI  - Preparation and characterization of monoclonal antibodies to proteins and other
      cellular components.

PMID- 7524946
TI  - Antibody against branched epitope as an affinity ligand to separate the parent
      protein.
AB  - A peptide that contained one of the continuous epitopes of recombinant human
      lymphotoxin (rhLT) (amino acid residues 139-154) has been located by epitope
      mapping. The branched form of this peptide was synthesized by the multiple
      antigen peptide procedure with an octameric branched resin and was subsequently
      used to elicit anti-epitope antibody in rabbits. The resulting anti-epitope was
      then used as an immunoaffinity ligand in affinity chromatography to purify the
      parent protein, rhLT, from the host cell lysate directly. It is suggested that
      this approach would be a general way to create novel biospecific ligands for
      affinity separations.

PMID- 7524945
TI  - High-dose intraperitoneal aprotinin treatment of acute severe pancreatitis: a
      double-blind randomized multi-center trial.
AB  - A multi-center double-blind trial was performed on 48 patients with severe acute
      pancreatitis. All patients were treated with intraperitoneal lavage. One group (n
      = 22) was also treated with high doses of the protease inhibitor, aprotinin
      (Trasylol; Bayer AG, Leverkusen, Germany) administered intraperitoneally. Eight
      patients died, giving a total mortality of 16.6%. No difference was observed
      between the two groups. Altogether, 12 patients were operated on, corresponding
      to 25%. In the group not treated with aprotinin, 6 patients were operated on
      because of pancreatic necrosis, compared with none in the treated group. The
      difference was statistically significant. There were no significant differences
      between the two groups with regard to organ failure or other complications. It
      was concluded that aprotinin counteracts the development of pancreatic necrosis
      when given intraperitoneally in high doses to patients with severe acute
      pancreatitis, thus reducing the need for surgical intervention in these patients.

PMID- 7524947
TI  - Capillary electrophoresis: separation and quantitation of reverse transcriptase
      polymerase chain reaction products from polio virus.
AB  - In the present study reverse transcriptase (RT) polymerase chain reaction (PCR)
      products were generated from the RNA of polio virus. The products of the RT-PCR
      were analyzed by slab-gel electrophoresis (SGE) on 4% agarose gels, and capillary
      electrophoresis (CE). CE separations were performed in a coated capillary
      containing a linear polyacrylamide. Samples were injected hydrodynamically or
      electrokinetically. Detection of the RT-PCR products on CE was by UV absorbance
      at (254 nm) or by laser-induced fluorescence (LIF). While SGE resulted in
      adequate separation of 163 and 97 base pair RT-PCR products, separation of the
      97, 71 and 53 base pair products was minimal. CE separations showed baseline
      resolution for all the above PCR products. Finally, it was possible to quantitate
      the amount of RT-PCR product by developing a standard curve showing a linear
      relationship between the amount of RNA used in the RT-PCR and the amount of
      product formed in the RT-PCR. These results suggest the greater resolution and
      enhanced sensitivity observed, together with the ease of quantitation, make CE a
      powerful alternative to SGE for the separation and quantitation of PCR products.

PMID- 7524948
TI  - High-performance liquid chromatographic measurement of cerebrospinal fluid
      tetrahydrobiopterin, neopterin, homovanillic acid and 5-hydroxindoleacetic acid
      in neurological diseases.
AB  - Cerebrospinal fluid (CSF) samples from patients with a variety of neurological
      disorders were assayed to determine the concentrations of tetrahydrobiopterin
      (BH4), the active cofactor of hydroxylases. Dihydroneopterin (NH2) and neopterin
      (N), which are linked with BH4 synthesis and are inflammatory biochemical
      markers, were also measured simultaneously in a number of patients. 5
      Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the main products
      of serotonin and dopamine breakdown, were analyzed in parallel whenever possible.
      As BH4 and NH2 are difficult to analyze owing to their instability, CSF samples
      were collected under special conditions to preserve the reduced BH4 and NH2.
      Liquid chromatographic assays and detection of the various substances measured
      also required particular precautions. BH4 concentrations were elevated in
      patients with neurological disorders such as syphilis and lupus-like disease and
      especially in an AIDS patient with neurological complications with an increased
      N/BH4 ratio.

PMID- 7524949
TI  - Use of capillary electrophoresis-isoelectric focusing for the determination of
      bovine hemoglobin variants.
AB  - A capillary electrophoretic technique was developed to monitor patterns of
      hemoglobin production in young calves subjected to multiple phlebotomies. The
      method is similar to one previously described for the determination of human
      hemoglobin variants in whole blood using isoelectric focusing. After a single
      collection of one-half the circulating blood volume, there were obvious
      alterations in hemoglobin chain variants. HbA levels diminished as blood loss
      increased with minimum values corresponding to maximum blood loss. HbF levels did
      not appear to be affected. Also visible during the regenerative process were
      atypical overlapping peaks preceding the normal hemoglobin peaks. At the
      conclusion of the 18-day study, most of the electropherograms had returned to
      initial states. These changes were found to be a sensitive indicator of
      accelerated erythropoiesis in contrast to the standard technique of total
      hemoglobin determination by colorimetric means.

PMID- 7524950
TI  - High-performance liquid chromatographic determination of catecholamine
      metabolites and 5-hydroxyindoleacetic acid in human urine using a mixed-mode
      column and an eight-channel electrode electrochemical detector.
AB  - An HPLC system for the simultaneous determination of acidic catecholamine
      metabolites, related compounds and 5-hydroxyindoleacetic acid (5-HIAA) in human
      urine was developed. A mixed-mode (C18/anion-exchange) column with isocratic
      elution using citrate buffer and an eight-channel electrochemical detector were
      used. Vanilmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy
      3-methoxyphenyllactic acid (vanillactic acid, VLA), homovanillic acid (HVA),
      vanillic acid (VA) and 5-HIAA in urine were determined simultaneously. Detection
      limits and inter (n = 5) and intra-assay (n = 5) coefficients of variation were
      satisfactory. The mean of analytical recoveries (n = 3, +/- C.V. (%)) were
      between 97 +/- 3.2 (VMA) and 105 +/- 4.8 (VA). Correlations between the
      analytical results for VMA, HVA and 5-HIAA obtained by an established method and
      the present method were satisfactory. The mean +/- 2 S.D. of the excretion rates
      of VMA, DOPAC, VLA, HVA, 5-HIAA and VA in urine from healthy adult volunteers
      were 0.61-4.36, 0.13-1.02, 0-0.35, 0.67-6.55, 0.50-5.14 and 0-0.55 mg/g
      creatinine, respectively.

PMID- 7524951
TI  - The developing human biliary system at the porta hepatis level between 29 days
      and 8 weeks of gestation: a way to understanding biliary atresia. Part 1.
AB  - The developing biliary system in normal human embryos from 29 days to 8 weeks
      post-fertilization was studied. The primitive extrahepatic bile duct that
      originates from the embryonic hepatic foregut diverticulum is in contact with the
      hepatic anlage from the start of organogenesis and remains so throughout the
      gestational ages examined. The primitive extrahepatic bile duct maintains
      continuity with the ductal plate from which intrahepatic bile ducts are
      eventually formed. Contrary to long-held concepts of biliary development, no
      'solid stage' of entodermal occlusion of the common bile duct lumen was found at
      any stage of gestation in the material investigated. Therefore, biliary atresia
      is not caused by incomplete vacuolization of the 'solid stage'.

PMID- 7524952
TI  - The developing human biliary system at the porta hepatis level between 11 and 25
      weeks of gestation: a way to understanding biliary atresia. Part 2.
AB  - In biliary atresia, inflammation and destruction of extrahepatic and intrahepatic
      bile ducts with eventual fibrous obliteration occurs, causing neonatal
      obstructive jaundice. The onset of the disorder may start antenatally and
      progress after birth, and the porta hepatis is a constant site of involvement. To
      date, little is known about the intrauterine development of the bile ducts at the
      porta hepatis. The present work gives an account of the developmental pattern of
      bile ducts at the level of the porta hepatis in the normal human fetus from the
      11th to the 25th weeks of gestation. It has been observed that the proximal
      portion of the hilar bile ducts derives from the intrahepatic biliary ductal
      plate. This occurs following a predictable remodeling sequence by which, from
      many ductal plate-derived ductules, those destined to become definitive bile
      ducts are enveloped in a concentric cuff of mesenchyma. Those which are not are
      deleted. The distal portions of the right and left main hepatic ducts develop
      from the extrahepatic bile duct. There was no gestational period in which the
      extrahepatic bile duct and the intrahepatic biliary system were separated.
      Furthermore, the developing intrahepatic bile ducts maintain luminal continuity
      with the common bile duct from the start of organogenesis. Biliary atresia may
      result from: (i) failure to establish a definitive type of bile duct; (ii)
      leakage of bile from primitive bile ducts resulting in an interstitial
      inflammatory reaction in the adjacent mesenchyma; and (iii) continuous
      proliferation of primitive bile ducts at the level of the porta hepatis beyond
      the 25th week of gestation, as a failed compensatory mechanism.

PMID- 7524953
TI  - Changes in neuropeptide-containing nerves in human colonic mucosa with
      inflammatory bowel disease.
AB  - The distribution abnormality of vasoactive intestinal polypeptide-containing
      nerves (VIP-nerves) and substance P-containing nerves (SP-nerves) was
      immunohistochemically investigated in the colonic mucosa with inflammatory bowel
      disease (IBD) in relation to colonic glands and blood vessels in the lamina
      propria. In active ulcerative colitis (UC), VIP- and SP-nerves decreased in
      severe inflammatory lesions. VIP-nerves were almost absent particularly around
      crypt abscesses. Even in resolving and quiescent UC, VIP-nerves still decreased,
      depending on the decrease of glands and blood vessels. On the other hand, both
      nerves increased in some hypervascular lesions. In the uninvolved mucosa of UC,
      they did not change their distribution. In Crohn's disease, the distribution
      abnormality of both nerves resembled that of UC. These results suggest that the
      changes in VIP- and SP-nerve distributions in the mucosa with IBD are subsequent
      to mucosal inflammation and damage. However, these peptides are known to be
      immunoregulators, and their distribution abnormalities may induce the disorder of
      immunoregulation in the IBD mucosa and cause the mucosal damage and/or
      chronicity.

PMID- 7524956
TI  - Specific and cross-reacting monoclonal antibodies to Bordetella parapertussis and
      Bordetella bronchiseptica lipopolysaccharides.
AB  - Three groups of monoclonal antibodies (mAbs) were produced that would be useful
      for immunochemical typing and diagnosis of infections due to Bordetella species,
      and for the structural analysis of their lipopolysaccharides. PP6, a
      representative of the first group, recognizes an epitope shared by smooth-type
      Bordetella parapertussis and Bordetella bronchiseptica lipopolysaccharides (LPS).
      This epitope is carried by structurally identical polymeric O-chains (POC)
      present on both LPS molecules. PP8 and PP9 are representatives of the second
      group of mAbs. The interaction of PP8 and PP9 with B. parapertussis and B.
      bronchiseptica LPS requires POC, but periodate-sensitive sugar units of the core
      are also involved in the binding. The mAb BRg1 belongs to the third group, and
      specifically recognizes B. bronchiseptica LPS. Binding and inhibition studies
      with various Bordetella LPS molecules, and with their polysaccharide fragments,
      indicated that BRg1 interacts with a structure located at the hinge between the
      POC and a core region of the B. bronchiseptica LPS containing periodate-resistant
      sugars. This suggests that the structures of the hinge regions of the B.
      parapertussis and B. bronchiseptica LPS are different.

PMID- 7524955
TI  - Serotoninergic control of prolactin secretion in prepubertal male rats.
AB  - The role of the serotoninergic system in the control of prolactin (PRL) secretion
      has been studied in prepubertal male rats. Serum PRL concentration was measured
      in 16-day-old male rats at different times after the administration of 5
      hydroxytryptophan (5-HTP), a precursor of serotonin (5-HT) synthesis, alone or in
      combination with fluoxetine, a specific inhibitor of 5-HT uptake; DL-p
      parachlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis; and 8-hydroxy-2
      (di-n-propylamino)tetralin (8-OH-DPAT), a selective agonist of 5-HT1A receptors.
      Also, serum PRL concentration and pituitary content were measured after 5-HTP
      administration in castrated males implanted with silastic capsules containing
      testosterone or 5 alpha-androstane-3 alpha,17 beta-diol (alpha-diol). We found
      that: the reduction in serotoninergic activity after PCPA administration did not
      modify serum PRL concentrations; the stimulatory effect of 5-HTP on PRL secretion
      was not observed before day 16; the effects of 5-HTP or 5-HTP and fluoxetine were
      similar in intact and orchidectomized males; a significant increase in PRL
      secretion took place after 8-OH-DPAT administration; the duration of the
      stimulatory effect of 5-HTP increased after alpha-diol treatment; and pituitary
      PRL content increased after 5-HTP injection in intact males and decreased in
      castrated males treated with testosterone or alpha-diol.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7524954
TI  - Thyrotropin receptor and leukocyte adhesion molecules in autoimmune thyroid
      disease: a study of their gene expression by northern blot analysis and in situ
      hybridization.
AB  - In order to characterize the role of leukocyte-activating antigens and other
      immunological parameters in autoimmune thyroid disease, mRNA levels of
      intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion
      molecule 1 (ELAM-1, E-selectin), invariant chain (Ii) and the thymic hormone
      thymosin beta (T beta 4) were investigated in 18 human thyroid glands, including
      eight Graves' thyroids, two Hashimoto's thyroids, two endemic goiters and six
      healthy controls. Northern blot analysis showed that in autoimmune thyroid
      disease, expression of ICAM-1 and T beta 4 was correlated to transcript levels of
      Ii, whereas in the healthy controls, expression of T beta 4, ICAM-1 and ELAM-1
      was low or nearly absent. ELAM-1 and TSH receptor (TSH-R) expression, the latter
      serving as a thyroid specific marker, was increased in some diseased gland but
      showed no relation to the immunological parameters mentioned above. Localization
      of the specific mRNAs by in situ hybridization demonstrated a cell-specific
      expression of TSH-R (thyrocytes), ELAM-1 (vascular endothelial cells) and T beta
      4 (cells of hematopoietic origin). In contrast, transcripts of Ii and ICAM-1 were
      found in thyrocytes, leukocytes and endothelial cells. Our results implicate a
      coordinate expression of ICAM-1, T beta 4 and Ii in autoimmune thyroid disease,
      yielding distinct cellular expression patterns. Differential expression of ICAM
      1, Ii and the TSH-R in thyroid epithelial cells indicates active regulatory
      events within the thyrocyte.

PMID- 7524957
TI  - Determination of neutralizing epitopes in variable domains I and IV of the major
      outer-membrane protein from Chlamydia trachomatis serovar K.
AB  - Chlamydia trachomatis is a leading cause of sexually transmitted diseases and a
      number of strategies have been developed to produce vaccines to prevent its
      transmission. The purpose of this study was to map the neutralizing epitopes of
      C. trachomatis major outer-membrane protein (MOMP) serovar K by using anti-MOMP
      antibodies and synthetic peptides. Seven anti-MOMP monoclonal antibodies and
      three polyclonal antisera were produced and characterized. Their fine specificity
      was defined by direct binding assay on 15 peptides of 10 amino acid residues,
      overlapping by five residues, corresponding to the four variable domains (VDI
      VDIV: residues 64-85, 139-160, 224-237 and 287-319) of MOMP serovar K. Our data
      confirmed that a neutralizing epitope is found in VDIV, defined by peptides K12
      and K13. This epitope is 296TTLNPTIAG304, which has never been reported as a
      neutralizing epitope of serovar K. Another neutralizing epitope, defined by
      peptide K2, has been identified in VDI. This epitope is in the same position as
      71VAGLEK76, a peptide with neutralizing activity found in serovar A, but they are
      not identical because antibodies against peptide K2 do not bind to this epitope.
      No neutralizing epitope was found in the two other variable domains (VDII and
      III). In summary, two neutralizing sites, one in variable domain I and one in
      variable domain IV, were identified in serovar K.

PMID- 7524959
TI  - Non-Alzheimer degenerative dementias.
AB  - The explosion of research aimed at exploring degenerative dementias in the past
      20 years has produced a great deal of knowledge concerning not only Alzheimer's
      disease but also other conditions referred to as non-Alzheimer degenerative
      diseases. The conditions reviewed here fall broadly into two main categories:
      diseases with focal (lobar) atrophy and diffuse Lewy body disease. These
      conditions, which are described more and more often in centers around the world,
      represent entities different from Alzheimer's disease not only from a clinical
      and pathological viewpoint, but also in terms of genetics and perhaps even in
      terms of therapeutic responses. In view of the numerous therapeutic trials
      currently underway, the distinction between Alzheimer's disease and non-Alzheimer
      degenerative diseases has acquired new importance.

PMID- 7524958
TI  - [The induction of alloantigen-specific cytotoxic T-lymphocytes by the intravenous
      immunization of mice].
AB  - It is shown possible to induce specific cytotoxic T-lymphocytes (CTL) in the
      course of intravenous (i.v.) immunization of Balb/c mice by 2000-rad-irradiated
      allogeneic C57Bl/6 splenocytes in a dose of 9 x 10(7). The induced CTL express
      Thy1.2+L3T4-Ly2+ cell surface markers. No correlation was observed between the
      level of cytotoxic activity and the ability to inhibit proliferation in the
      population of lymphocytes primed by i.v. immunization.

PMID- 7524960
TI  - Molecular mechanisms of developmental and tumor angiogenesis.
AB  - Angiogenesis, the sprouting of capillaries from preexisting vessels, is of
      fundamental importance during embryonic development and is the principal process
      by which the brain and certain other organs become vascularized. Angiogenesis
      occurs during embryonic development but is almost absent in adult tissues.
      Transient and tightly controlled (physiological) angiogenesis in adult tissues
      occurs during the female reproductive cycle and during wound healing. In
      contrast, pathological angiogenesis is characterized by the persistent
      proliferation of endothelial cells, and is a prominent feature of diseases such
      as proliferative retinopathy, rheumathoid arthritis, and psoriasis. In addition,
      many tumors are able to attract blood vessels from neighbouring tissues. Tumor
      induced angiogenesis requires a constitutive activation of endothelial cells.
      These endothelial cells dissolve their surrounding extracellular matrix, migrate
      toward the tumor, proliferate, and form a new vascular network, thus supplying
      the tumor with nutrients and oxygen and removing waste products. The onset of
      angiogenesis in human gliomas is characterized by the expression of genes
      encoding angiogenic growth factors such as vascular endothelial growth factor
      (VEGF), platelet-derived growth factor (PDGF) in tumor cells, and coordinate
      induction of genes in endothelial cells which encode the respective growth factor
      receptors. Developmental and tumor angiogenesis appear to be regulated by a
      paracrine mechanism involving VEGF and VEGF receptor-1 and -2.

PMID- 7524962
TI  - Acidic fibroblast growth factor is expressed abundantly by photoreceptors within
      the developing and mature rat retina.

PMID- 7524961
TI  - Axons regenerate with correct specificity in horizontal slice culture of the
      postnatal rat entorhino-hippocampal system.
AB  - We have used slice culture of the entorhino-hippocampal system to investigate (1)
      whether nerve fibres which are cut postnatally are able to regenerate and (2)
      whether the regenerating fibres are able to establish correct selective target
      specificity in the formation of their terminal fields. Slices of tissue were
      taken in the horizontal plane through the caudo-ventral pole of the cerebral
      hemisphere of 9- to 10-day-old rats. Such slices maintain the entorhinal cortex
      in continuity with the hippocampus and intervening retrohippocampal areas.
      However, because of the dorsal inclination of the entorhino-hippocampal
      projection fibres in situ, the segments of the entorhinal cortex and hippocampus
      contained within each individual horizontal slice were disconnected from each
      other. During subsequent culture, the formation of fibre connections between the
      entorhinal area and the hippocampal complex was studied by the extracellular and
      intracellular anterograde transport of biocytin or biotin dextran, the retrograde
      transport of biotin dextran or carbocyanine dyes, and by electrical stimulation
      and recording. For the first 24 h after taking the slice, there were no
      entorhinal projections beyond the deep white matter, and no fibres reached the
      hippocampus or dentate gyrus. After 3 days in culture a small number of growing
      fibres had perforated the subiculum and entered the target areas. Between 6 and
      14 days these projections increased and matured. As in the normal adult brain,
      entorhinal layer II stellate cells projected correctly to the dentate gyrus and
      hippocampal field CA3, whereas layer III pyramidal cells projected to hippocampal
      field CA1 and the subiculum. The new fibres grew along both alvear and perforant
      pathways. Anterograde and retrograde labelling showed that the reciprocal
      projections from the pyramidal cells of the subiculum and CA1 to the entorhinal
      area had also been severed at the time of taking the slices, and had similarly
      regenerated. Our results demonstrate that by taking tissue slices in appropriate
      planes it is possible to study the regeneration of axons in the tissue
      environment through which they normally run. This approach avoids the use of
      coculture and the concomitant difficulties associated with the need for fibres to
      cross a coculture interface. In horizontal slices of postnatal tissue, severed
      fibre projections between the entorhinal cortex and the hippocampal complex can
      regenerate in both directions and re-establish their correct laminar, pathway and
      target specificity.

PMID- 7524963
TI  - Intracortical regionality represented by specific transcription for a novel
      protein, latexin.
AB  - The monoclonal antibody (mAb) PC3.1 recognizes a subset of neurons distributed in
      the infragranular layers of the lateral neocortex of the rat. Immunoaffinity
      chromatography with mAb PC3.1 showed that this antibody specifically binds a
      peptide epitope on a 29 kDa protein named latexin. To study the molecular details
      of the protein, we isolated four independent cDNA clones for latexin from cDNA
      libraries of the rat cerebral cortex and whole brain using the amino acid
      sequences of latexin fragments. Analysis of these cDNA clones showed that the
      predicted primary structure of latexin consists of 223 amino acids, and has no
      strict homology to any sequences so far known. Western and Northern blots
      demonstrated that the latexin and its mRNA were expressed predominantly in neural
      tissues with some expression in non-neural tissues. The gene that encodes latexin
      in the rat appeared to have homologues in other mammalian species and in the
      chick. In situ hybridization showed that latexin mRNA is synthesized in a subset
      of neurons in the lateral but not the dorsal neocortex, and that the distribution
      profile of these neurons is quite similar to that of neurons expressing latexin.
      These results indicate that latexin is a novel class of neuronal protein which
      represents intracortical regionality, and suggest that the regional specification
      of the neocortex involves selective parcellation of neurons which express a
      particular gene.

PMID- 7524964
TI  - Rectification properties and Ca2+ permeability of glutamate receptor channels in
      hippocampal cells.
AB  - Excitatory amino acids exert a depolarizing action on central nervous system
      cells through an increase in cationic conductances. Non-NMDA receptors have been
      considered to be selectively permeable to Na+ and K+, while Ca2+ influx has been
      thought to occur through the NMDA receptor subtype. Recently, however, the
      expression of cloned non-NMDA receptor subunits has shown that alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are permeable to Ca2+
      whenever the receptor lacks a particular subunit (edited GluR-B). The behaviour
      of recombinant glutamate receptor channels predicts that Ca2+ would only permeate
      through receptors that show strong inward rectification and vice versa, i.e. AMPA
      receptors with linear current-voltage relationships would be impermeable to Ca2+.
      Using the whole-cell configuration of the patch-clamp technique, we have studied
      the Ca2+ permeability and the rectifying properties of AMPA receptors, when
      activated by kainate, in hippocampal neurons kept in culture or acutely
      dissociated from differentiated hippocampus. Cells were classified according to
      whether they showed outward rectifying (type I), inward rectifying (type II) or
      almost linear (type III) current-voltage relationships for kainate-activated
      responses. AMPA receptors of type I cells (52.2%) were mostly Ca(2+)-impermeable
      (PCa/PCs = 0.1), while type II cells (6.5%) expressed Ca(2+)-permeable receptors
      (PCa/PCs = 0.9). Type III cells (41.3%) showed responses with low but not
      negligible Ca2+ permeability (PCa/PCs = 0.18). The degree of Ca2+ permeability
      and inward rectification were well correlated in cultured cells, i.e. more inward
      rectification corresponded to higher Ca2+ permeability.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7524966
TI  - Comparison of stress-induced changes in noradrenergic and serotonergic neurons in
      the rat hippocampus using microdialysis.
AB  - The effects of stress on the serotonergic and noradrenergic projection to the
      hippocampus were compared in freely moving rats using microdialysis. Stress
      induced changes in 5-hydroxytryptamine (5-HT), noradrenaline and their
      metabolites 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic
      acid (DOPAC) were measured in the presence of their respective uptake blockers.
      Local infusion of tetrodotoxin and replacement of Ca2+ with Cd2+ were used to
      test dependence on impulse traffic. A 5 min tail pinch or 10 min restraint stress
      increased 5-HT, 5-HIAA, noradrenaline and DOPAC levels. A subcutaneous saline
      injection produced an increase in 5-HT and DOPAC but not noradrenaline or 5-HIAA.
      Although alpha 2 adrenoceptor agonists and antagonists produced changes in the
      baseline values of noradrenaline and DOPAC, they had little or no effect on
      stress-induced changes. Both the abolition of impulse traffic and its enhancement
      by stress had a greater effect on transmitter than on metabolite levels. Although
      the responses to stress of the noradrenergic and serotonergic pathway showed many
      similarities, there was evidence for their activation by separate pathways.

PMID- 7524965
TI  - Requirement of metabotropic glutamate receptors for the generation of
      inflammation-evoked hyperexcitability in rat spinal cord neurons.
AB  - In the central nervous system the transmitter L-glutamate activates both
      ionotropic receptors coupled to cation channels and metabotropic receptors
      coupled to G-proteins. The role of metabotropic receptors in the processing of
      mechanosensory and nociceptive information was studied in a subset of spinal cord
      neurons with afferent input from the knee joint in anaesthetized rats using
      electrophysiological methods. The ionophoretic administration of L-2-amino-3
      phosphonopropionic acid (L-AP3), an antagonist at the metabotropic receptor, had
      no effect on the responses to innocuous and noxious pressure applied to the
      normal knee joint, although the antagonist prevented the potentiation of these
      responses evoked by the ionophoretic administration of a specific agonist at the
      metabotropic receptor, trans-(+/-)-1-amino-(1S,3R)-cyclopentane-dicarboxylic acid
      (t-ACPD). By contrast, in neurons that were rendered hyperexcitable by acute
      inflammation in the knee joint L-AP3 reduced the responses to pressure applied to
      the knee. When L-Ap3 was applied during induction of inflammation and throughout
      the subsequent 1.5 h the spinal neurons did not develop hyperexcitability over
      this time period. L-AP3 did not impair the activation of ionotropic N-methyl-D
      aspartate (NMDA) and non-NMDA receptors by the specific agonists. We conclude
      that spinal metabotropic glutamate receptors are not involved in the mediation of
      responses to innocuous and noxious mechanical stimuli applied under normal
      conditions. They are required, however, for the generation of inflammation-evoked
      hyperexcitability of spinal cord neurons, a form of functional plasticity
      underlying the painfulness in pathophysiological conditions such as inflammation.

PMID- 7524967
TI  - Anatomical and electrophysiological evidence for an excitatory amino acid pathway
      from the thalamic mediodorsal nucleus to the prefrontal cortex in the rat.
AB  - This study was undertaken to identify the neurotransmitter of the projection from
      the thalamic mediodorsal nucleus (MD) to the prefrontal cortex (PFC) using both
      retrograde transport of D-[3H]aspartate and electrophysiological approaches in
      the rat. Unilateral microinjections of D-[3H]aspartate performed into the
      prelimbic area of the PFC resulted in dense labelling of numerous cells in the
      ipsilateral MD. Excitatory responses were observed in PFC neurons after
      electrical stimulation of the MD. However, since cortical neurons project to the
      MD, these excitatory responses could have resulted either from the activation of
      the MD-PFC pathway and/or from the activation of recurrent collaterals of
      antidromically driven cortico-thalamic fibres. The conduction time of each of
      these two reciprocal pathways was determined by antidromic activation. Short
      latency excitatory responses resulted from activation of the MD-PFC pathway. They
      were predominantly observed in PFC neurons located in layer III and evoked at low
      frequency stimulation (0.3-1 Hz). These excitatory responses disappeared or were
      replaced by longer latency responses when higher frequency stimulations (3-10 Hz)
      were used. MD-evoked responses were blocked by the iontophoretic application of
      the AMPA receptor antagonist CNQX into the PFC. These results indicate that the
      MD-PFC pathway utilizes glutamate and/or aspartate as the neurotransmitter and
      that its activation induces excitation in PFC neurons through AMPA receptors.
      Even though the local application of the NMDA receptor antagonist APV was
      ineffective, a contribution of these receptors in MD-PFC transmission cannot be
      excluded.

PMID- 7524968
TI  - [Ophthalmological manifestations of infantile Refsum's disease: apropos of 3
      cases].
AB  - We describe the ophthalmic manifestations of 3 cases of infantile Refsum's
      disease. The gravity and the aspect of the retinal disorders which we have
      observed by ophthalmoscopy and electroretinography were quite different from one
      case to another, including two siblings. We then go on to discuss the pathogeny
      and the genetic basis of diseases due to a deficiency of the peroxisomal
      biogenesis.

PMID- 7524971
TI  - Handling difficult questions in palliative care--a flow diagram.
AB  - Patients with advanced disease ask many difficult questions, some of which have
      painful answers, some of which have answers which contain uncertainty, and some
      of which have no answers. They should be able to ask their questions in an
      environment that allows them to disclose their true worries, have the opportunity
      to talk them through, and look for options. Health professionals need to develop
      the relevant skills to help patients and their families to disclose and discuss
      difficult issues, while handling their own emotions.

PMID- 7524969
TI  - The spiritual component of palliative care.
AB  - This article discusses the concept of spirituality within palliative care. It
      considers aspects of religion and creativity in relation to spirituality, which
      may be inter-related as well as being significant in their own right. The nurse's
      role within the interdisciplinary team is explored. The expertise required as
      well as the emotional effect on nurses offering spiritual support is described.

PMID- 7524970
TI  - The impact on community palliative care services of a hospital palliative care
      team.
AB  - This retrospective study examined the influence of a hospital palliative care
      team on the activity of a local hospice home care team over a four-year period
      from May 1989 to April 1993 in East Leeds. The increasing referral to death
      interval observed in home care patients over this period appears to be due to the
      presence of the hospital team. The increasing work-load of the home care team
      generated by the hospital team is discussed with reference to solutions to meet
      this increasing demand. A district or regional planning strategy is recommended
      to co-ordinate existing and potential palliative care services.

PMID- 7524972
TI  - Soluble form of P-selectin in patients with acute myocardial infarction.
AB  - BACKGROUND: P-selectin, an integral membrane glycoprotein of platelets and
      endothelial cells, is rapidly redistributed to the cell surface after cellular
      activation. The soluble form of P-selectin has been shown to be present in people
      with normal circulation. The purpose of the present study was therefore to
      examine the soluble form of P-selectin in patients with acute myocardial
      infarction (AMI). METHODS: Whole blood was obtained from nine patients with AMI
      and from 10 volunteers who made up the control group. Plasma concentrations of
      the soluble form of P-selectin were examined with a monoclonal antibody-based
      enzyme immunoassay. RESULTS: Plasma P-selectin levels in control volunteers were
      178 +/- 44 ng/ml. In patients with AMI, plasma P-selectin levels on days 1, 2 and
      3 were 743 +/- 374, 627 +/- 267, and 588 +/- 223 ng/ml, respectively (P < 0.001)-
      significantly higher than the levels in the control volunteers. CONCLUSION:
      Plasma concentrations of the soluble form of P-selectin were markedly higher in
      patients with AMI, suggesting the activation of platelets, or endothelial cells,
      or both. Thus, quantitative measurements of plasma P-selectin concentrations may
      help to assess the pathophysiology of inflammatory reactions in patients with
      AMI.

PMID- 7524973
TI  - Role of adhesion molecules in leukocyte binding to endothelial cells adherent to
      vascular grafts.
AB  - BACKGROUND: The localization of leukocytes to vascular grafts is an essential
      part of healing and infection resistance. The mechanisms involved in this process
      are only partly understood. STUDY DESIGN: Human saphenous vein endothelial cells
      (HSVEC) were grown on control polystyrene culture ware and expanded
      polytetrafluoroethylene (ePTFE). The binding of monoclonal antibodies against the
      intercellular adhesion molecule (ICAM-1) and the E-selectin by adherent HSVEC was
      determined by flow cytometry. Peripheral blood leukocytes (PBL) were cocultured
      with HSVEC adherent to ePTFE and leukocyte binding was determined with and
      without the addition of a protein kinase C inhibitor. RESULTS: HSVEC adherent to
      ePTFE constitutively bound anti-ICAM-1 antibodies, which were attenuated by the
      protein kinase C inhibitor, H-7. HSVEC adherent to ePTFE bound significantly
      greater numbers of leukocytes than those on control (58 versus 41 percent, p <
      0.05). Incubation with H-7 decreased leukocyte binding to HSVEC significantly (p
      < 0.005). Coculture of PBL with HSVEC adherent to ePTFE caused a tenfold increase
      in binding of anti-E-selectin antibodies (p < 0.0005). CONCLUSIONS: These data
      indicate that PBL binding to HSVEC adherent to ePTFE is, at least in part, ICAM-1
      to HSVEC adherent to ePTFE is, at least in part, ICAM-1 and E-selection
      dependent.

PMID- 7524974
TI  - Quality of palliation and possible benefit of extra-anatomic reconstruction in
      recurrent dysphagia after resection of carcinoma of the esophagus.
AB  - BACKGROUND: After "curative" resection of carcinoma of the esophagus, late
      secondary dysphagia almost invariably indicates locoregional tumor recurrence.
      The retrosternal reconstruction route is advocated to prevent ingrowth of tumor
      recurrence in the neoesophagus. STUDY DESIGN: To evaluate the quality of
      palliation after "curative" resection of carcinoma of the esophagus and the
      possible benefit of the retrosternal reconstruction route, we retrospectively
      analyzed the records of patients who had resection of a malignant tumor of the
      esophagus, or the gastroesophageal junction, and a prevertebral reconstruction.
      The extra-anatomic route would have been only beneficial for patients with
      intrathoracic tumor recurrence distant from the anastomosis and causing
      gastrointestinal symptoms. RESULTS: Between 1983 and 1989, 209 patients (mean age
      of 61.3 years at the time of operation) had "curative" resection and prevertebral
      reconstruction in the institution of this study. Seventy-three patients (35
      percent) had locoregional tumor recurrence. Univariate and multivariate analysis
      of various risk factors for locoregional recurrence showed that the presence of
      positive lymph nodes (pN1), especially if located at the celiac trunk (pM1), and
      a macroscopically non-radical R2 resection were the most important risk factors.
      Forty-six patients (22 percent) had secondary dysphagia as a result of
      locoregional tumor recurrence, mostly (18 percent) within two years
      postoperatively. Dysphagia lasted on average 5.3 months (range of 0.3 to 21.5
      months) before the patients died. In 27 patients (13 percent), dysphagia would
      probably have been prevented by using a retrosternal reconstruction route.
      CONCLUSIONS: These data are an argument in favor of the extra-anatomic,
      retrosternal reconstruction route after limited transthoracic or transhiatal
      resection in the presence of positive lymph nodes. This method seems especially
      indicated if the nodes are located at the celiac trunk and in case of a
      macroscopically nonradical R2 resection.

PMID- 7524975
TI  - Diagnostic value of the molecular genetic detection of the t(11;22) translocation
      in Ewing's tumours.
AB  - One consistent feature of the Ewing's tumour family is the presence of a balanced
      translocation involving band q12 and band q24 of chromosome 22 and chromosome 11.
      Recent cloning of the chromosome breakpoint regions of t(11;22)(q24;q12) Ewing's
      sarcoma translocation has revealed that the breakpoints were localized within the
      Ewing's sarcoma gene (EWS gene) on chromosome 22 and the Fli-1 gene on chromosome
      11. Molecular genetic techniques can thus be applied to the detection of the
      t(11;22) translocation in Ewing's tumours. By reverse transcription and
      polymerase chain reaction technique (RT-PCR) 11 Ewing's tumour derived cell
      lines, 12 primary Ewing's tumours, and 11 tumours after treatment were analysed
      for the occurence of the t(11;22) translocation. Furthermore, blood and bone
      marrow samples from 5 patients were available for RT-PCR. In 78% of the cell
      lines and 91% of the primary Ewing's tumours the t(11;22) translocation was
      detectable by RT-PCR. In bone marrow samples from a Ewing's sarcoma patient
      presenting in relapse tumour cells were detected by molecular genetic analysis.
      Our results indicate that molecular genetic detection of the t(11;22)
      translocation is valuable in the differential diagnosis of small round cell
      tumours and will provide important information for the staging and prognosis of
      Ewing's tumour.

PMID- 7524976
TI  - Detection of keratin subtypes in routinely processed cervical tissue:
      implications for tumour classification and the study of cervix cancer aetiology.
AB  - We investigated the expression of keratin subtypes 7, 8, 10, 13, 14, 17, 18 and
      19 in the normal cervix, in cervical intraepithelial neoplasia (CIN) lesions and
      in cervical carcinomas, using a selected panel of monoclonal keratin antibodies,
      reactive with routinely processed, formalin fixed paraffin embedded tissue
      fragments. The reaction patterns derived for each keratin antibody were compared
      with known expression patterns of the various epithelia, previously examined in
      frozen tissues. Although the reactivity of the antibodies was generally
      acceptable, considerable modifications to the manufacturers' staining
      instructions were often necessary. For some antibodies, which were previously
      thought to be reactive with fresh frozen tissue only, we developed staining
      protocols rendering them reactive with routinely processed material. As with
      previous findings in frozen sections we observed increasing expression of
      keratins 7, 8, 17, 18 and 19 with increasing grade of CIN. In cervical carcinomas
      the differences in keratin detectability between the main categories were more
      pronounced than in frozen sections, probably due to fixation and processing. For
      routine pathology, keratin phenotyping of cervical lesions may be of value in
      classification. The fact that keratin 7 was detected for the first time in
      reserve cells, and that this keratin was also found to be expressed in a
      considerable number of CIN lesions and cervical carcinomas supports the
      suggestion that reserve cells are a common progenitor cell for these lesions.

PMID- 7524978
TI  - Characterization of a serum factor that decreases albumin mRNA in cultured
      hepatocytes.
AB  - When primary cultures of hepatocytes are exposed to media containing fetal bovine
      serum (FBS) there is a rapid decrease in levels of tissue-specific mRNAs such as
      albumin mRNA. We used Northern blot analysis to examine mRNA levels in cultured
      hepatocytes, and characterized the factor in FBS that significantly reduces the
      steady state albumin mRNA level. Neonatal bovine serum or serum derived from
      platelet-poor calf plasma proved as potent as did FBS, but commercial bovine
      serum albumin did not exhibit this inhibitory activity. Inhibitory activity of
      FBS was not removed by moderate heat treatment, dialysis, or extraction with
      organic solvents. However, incubation of FBS with a highly anionic detergent such
      as 0.1% sodium dodecyl sulfate or N-lauroyl sarcosine, followed by extensive
      dialysis, resulted in sera that did not inhibit expression of albumin mRNA. These
      sera supported cell attachment and seemed non-toxic toward the cells. Ammonium
      sulfate fractionation of FBS showed the activity was present in the 45 to 70%
      fraction, and trypsin digestion destroyed the inhibitory activity. Gel exclusion
      chromatography gave a molecular weight of 60,000 to 70,000. Fractionation of
      serum proteins by DEAE-Sephacel or Cibacron blue-agarose showed enrichment for
      albumin in the most active fractions. Interestingly, metabolic labeling of
      secreted and cellular proteins with 35S-methionine and cysteine showed no
      significant difference between hepatocytes maintained for 2 days beforehand in
      serum-free or serum-supplemented media, and no difference between detergent
      treated FBS and control FBS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524977
TI  - Synoviocytes in chronic synovitis in situ and cytokine stimulated synovial cells
      in vitro neo-express alpha 1, alpha 3 and alpha 5 chains of beta 1 integrins.
AB  - The expression of the beta 1 integrins was examined immunohistochemically in
      synoviocytes from normal synovitis membrane and from chronic synovitis of
      different aetiology and intensity. Normal synoviocytes were alpha 6 beta 1
      positive but lacked alpha 1 through alpha 5. In mild inflammation type A
      synoviocytes neo-expressed alpha 1, alpha 3, and alpha 5 chains. In severe
      inflammation both type A and B synoviocytes expressed alpha 3, alpha 4, alpha 5,
      and alpha 6 chains. The effects of inflammatory cytokines, as single agents or in
      combination, on the beta 1 integrin expression in cultured normal synoviocytes
      was determined by immunocytochemistry and flow cytometry. The alpha 1 chain,
      while absent in unstimulated synoviocytes, was induced by interleukin-1 beta (IL
      1 beta), tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN
      gamma). This effect was enhanced by combining IL-1 beta and TNF-alpha. Expression
      of the alpha 3 chain was up-regulated by IL-1 beta and, more intensely, by IFN
      gamma. Transforming growth factor beta (TGF-beta) inhibited the up-regulating
      effect of IL-1 beta and antagonized the effect of IFN-gamma on alpha 3 chain
      expression. Expression of the alpha 5 chain was up-regulated significantly by co
      stimulation through IL-1 beta together with TGF-beta or TNF-alpha. Thus, the beta
      1 integrin profile of cytokine activated synoviocytes in vitro resembled that of
      synoviocytes in synovitis in situ. These data suggest that IL-1 beta, TNF-alpha,
      IFN-gamma, and TGF-beta are likely to be among the effectors regulating beta 1
      integrin expression in synoviocytes in vivo.

PMID- 7524981
TI  - NADPH-diaphorase activity as a marker for nitric oxide synthase in neurons of the
      guinea pig respiratory tract.
AB  - Recent studies in physiology have suggested that part of the inhibitory
      nonadrenergic noncholinergic (iN-ANC) response of airway smooth muscle is
      mediated by nitric oxide (NO). To examine this point morphologically, the guinea
      pig respiratory tract was investigated histochemically for nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase (NADPH-d), a marker for NO synthase
      (NOS). In addition, coexpression of NOS and vasoactive intestinal peptide (VIP)
      or calcitonin gene-related peptide (CGRP) was studied using a combination of
      histochemistry for NADPH-d and immunohistochemistry for VIP or CGRP. Nerve fibers
      showing NADPH-d activity were abundantly observed in the respiratory tract. They
      were distributed throughout smooth-muscle bundles, lamina propria, submucosal
      glands, and around bronchial and pulmonary arteries. NADPH-d-containing nerve
      cell bodies were occasionally found within airway ganglia. The colocalization
      study demonstrated that NADPH-d-containing nerve fibers frequently coincided with
      VIP-like immunoreactive nerve fibers but not with CGRP-like immunoreactive nerve
      fibers. Among nonneural tissues, NADPH-d activity was noticed in the endothelium
      of both bronchial and pulmonary vessels, and in the pleura. These observations
      indicated that NO may be produced by neurons and vascular endothelium of the
      guinea pig respiratory tract, and may function as a neuronal mediator as well as
      endothelium-derived relaxing factor (EDRF). Colocalization of NADPH-d and VIP
      like immunoreactivity in nerve fibers suggested that NO and VIP may function as
      cotransmitters.

PMID- 7524979
TI  - Potassium channel opener, YM 934, inhibits neurogenic plasma leakage in guinea
      pig airways.
AB  - The effect of a potassium channel opener, YM 934, on neurogenic airway plasma
      leakage was examined in anesthetized guinea pigs. Airway plasma leakage was
      evoked by stimulation of both vagal nerves in the presence of atropine (1 mg/kg,
      intravenous) and propranolol (1 mg/kg, intravenous), and was measured by
      extravasation of Evans blue dye (30 mg/kg, intravenous) in trachea (Tr), main
      bronchi (MB), and central (cIPA) and peripheral intrapulmonary airways (pIPA).
      Vagal stimulation significantly increased the dye leakage in all portions of the
      airway. YM 934 (10, 30, and 100 micrograms/kg, intravenous) inhibited vagally
      induced plasma leakage in Tr, MB, cIPA, and pIPA, and this inhibitory effect of
      YM 934 was reduced by the ATP-sensitive potassium channel blocker, glibenclamide
      (25 mg/kg, intravenous). By contrast, YM 934 (100 micrograms/kg, intravenous) had
      no inhibitory effect on exogenous substance P (0.5 and 1 micrograms/kg,
      intravenous)-induced plasma leakage in any parts of the airway. These results
      indicate that YM 934 inhibits airway neurogenic inflammation by modulating the
      release of neuropeptides from the sensory nerve endings, and that the inhibitory
      effect can be attributed to the potassium channel opening activity of this
      compound.

PMID- 7524980
TI  - Dexamethasone and oxytetracycline reverse the potentiation of neurogenic
      inflammation in airways of rats with Mycoplasma pulmonis infection.
AB  - Mycoplasma pulmonis infection in rats causes a chronic inflammatory airway
      disease. Along with extensive remodeling of the airway mucosa, lymphocytic
      infiltrates, angiogenesis, and mucosal thickening, there is an abnormal
      sensitivity of the blood vessels to mediators that evoke "neurogenic
      inflammation". As a result, substance P, a peptide released from sensory nerves,
      produces an unusually large amount of plasma leakage. These changes can be
      prevented or reduced by prophylactic treatment with antibiotics, but it is
      unknown whether the extensive remodeling of the airway mucosa and potentiation of
      neurogenic inflammation can be reversed once they are established. We addressed
      this issue in F344 rats that were infected with M. pulmonis at 8 wk of age. Six
      weeks later, the rats were treated daily with an antibiotic (oxytetracycline, 20
      mg/kg intramuscularly), to reduce the number of infecting organisms, or with an
      antiinflammatory steroid (dexamethasone, 0.5 mg/kg intraperitoneally), to reduce
      the inflammatory and immunologic response to the infection. Sham-treated infected
      rats received daily injections of 0.9% NaCl. After 1, 2, or 4 wk of treatment the
      rats were anesthetized and then challenged with substance P (5 micrograms/kg
      intravenously). The sham-treated rats had pathologic changes in their airways
      typical of severe M. pulmonis infection, and had as much as a threefold increase
      in substance P-induced plasma leakage. By comparison, after 4 wk of treatment
      with oxytetracycline or dexamethasone, the chronic inflammation was nearly
      resolved and the response to substance P was in the normal range. Unexpectedly,
      dexamethasone, like oxytetracycline, reduced the number of infecting
      organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7524982
TI  - Modulation of hemodynamics and organ blood flow by nitric oxide synthase
      inhibition is not altered in normotensive, septic rats.
AB  - Hyperdynamic sepsis is associated with a redistribution of organ blood flow. We
      hypothesized that increased nitric oxide (NO) production could mediate this
      process. The objective of this study was to determine the effect of a NO
      synthesis inhibitor on systemic and organ blood flows in vivo in septic and in
      normal rats. Rats were instrumented for hemodynamic monitoring and randomized to
      undergo cecal ligation and perforation (CLP) or control laparotomy. Cardiac
      output and organ blood flow were measured by thermodilution and radioactive
      microspheres, respectively. Baseline values were obtained at 24 h after CLP or
      control laparotomy and after the administration of L-nitro-arginine methyl ester
      (L-NAME) at 2, 4, 8, and 16 mg/kg intravenously. All studies were performed in
      awake, unrestrained animals. Septic animals were normotensive and hyperdynamic. L
      NAME decreased cardiac index and increased systemic vascular resistance and mean
      arterial blood pressure to an equivalent degree in control and in CLP animals.
      CLP was associated with significantly increased relative blood flow to the small
      bowel and portal circulation. Although cardiac output decreased with L-NAME,
      blood flow to the diaphragm, liver, and brain was relatively well preserved.
      Absolute blood flow to other organs, including small bowel, decreased in parallel
      to the cardiac output. The effect of L-NAME on organ blood flow was comparable in
      control and in CLP animals. We conclude that the influence of NO on organ blood
      flows appears to vary between organs, but that NO does not explain the
      redistribution of blood flow observed in hyperdynamic sepsis.

PMID- 7524983
TI  - Liposome encapsulation improves the effect of antifibrotic agent in rat lung
      fibrosis.
AB  - We studied whether the therapeutic efficacy of the antifibrotic agent cis-4
      hydroxy-L-proline (cHyp) in preventing bleomycin-induced pulmonary fibrosis in
      rats is enhanced by intratracheal delivery in liposomes. Dual-radiolabeled
      liposomes were used to study the distribution and stability of liposomes after
      intratracheal instillation. Lung retention was > 20% 1 wk after intratracheal
      instillation of 9 mumol phospholipid, and liposomes were intact as indicated by
      the ratio of the lipid and aqueous-phase markers remaining unchanged. For the
      fibrosis study, groups of rats were instilled with 1.2 U bleomycin (Bleo) and
      treated 1 and 2 wk later by single intratracheal instillation of test compounds.
      The control group received 0.3 ml saline (Bleo/sal). The treated groups received
      9 mumol phospholipid in 0.3 ml of the following liposome preparations: empty
      liposomes (Bleo/lip), liposomes and 100 mg/kg of free unencapsulated cHyp
      (Bleo/lip/cHyp), and 100 mg/kg of liposome-encapsulated cHyp (Bleo/lip-cHyp). At
      3 wk, fibrosis (mg hydroxyproline/g weight lung) by groups was as follows:
      control, 2.6 +/- 0.1 (SEM); Bleo/sal, 3.2 +/- 0.1, Bleo/lip, 3.2 +/- 0.1, and
      Bleo/lip/cHyp, 3.1 +/- 0.1, p < 0.05 compared with control; Bleo/lip-cHyp, 2.6 +/
      0.1, p < 0.05 compared with Bleo/sal, n = 3 to 6. Histologic grading of fibrosis
      did not show decreased fibrosis in the Bleo/lip-cHyp group, probably because of
      the focal nature of the fibrotic lesions. We conclude that cHyp encapsulated in
      liposomes prevents bleomycin-induced fibrosis by biochemical measurements.
      Delivery of antifibrotic agents to the lung in carrier vehicles promotes
      retention and may enhance their efficacy in treating bleomycin-induced pulmonary
      fibrosis.

PMID- 7524984
TI  - Allergen-specific challenge induces intercellular adhesion molecule 1 (ICAM-1 or
      CD54) on nasal epithelial cells in allergic subjects. Relationships with early
      and late inflammatory phenomena.
AB  - Intercellular adhesion molecule 1 (ICAM-1 or CD54) expression on epithelial cells
      (EC) has been demonstrated to play a role in the local molecular events of
      inflammation following allergen-specific conjunctival challenge. In the light of
      these observations, we evaluated the possible expression of ICAM-1 on nasal EC
      after allergen-specific challenge. Three groups of subjects were studied: (1) 14
      symptomless patients sensitized to mites, (2) 15 symptomless patients sensitized
      to pollen, and (3) 10 healthy volunteers as controls. The study was performed
      during winter. At baseline we found that both pollinosic and healthy subjects did
      not express CD54 on epithelial cells, whereas mite-sensitive patients showed a
      mild expression (possibly caused by a persistent natural allergen exposure). In
      addition, clinical and cellular responses were induced by lower allergen dosages
      in mite-sensitive patients compared with pollen-sensitive patients. CD54 was
      detectable in all the allergic patients but not in the control subjects 30 min
      after challenge. At 6 h all patients showed a marked inflammatory infiltration
      and CD54 persistence on EC: such an infiltration was more relevant in patients
      developing clinical late-phase reaction (LPR). Finally, 24 h after challenge EC
      CD54 expression persisted, as well as a cellular infiltrate mainly caused by
      eosinophils (the latter being more pronounced in mite-sensitive individuals).
      CD54 should be regarded as an early and sensitive marker of inflammation in both
      LPR-positive and LPR-negative patients. A cellular inflammatory infiltrate was
      detectable in both LPR-positive and LPR-negative subjects, although relevant
      differences in eosinophil counts were observed between the two groups. The study
      emphasizes the importance of the different events of inflammation in allergy.

PMID- 7524985
TI  - Treatment of chronic viral hepatitis: the end of the beginning?

PMID- 7524986
TI  - Free transplantation of fat autografts expanded by tissue expanders in rats.
AB  - Inguinal fat pads of 28 rats were expanded by tissue expanders for 10 days and
      transplanted to the back of the same animal. The non-expanded contralateral
      inguinal fat pads were also transplanted and served as controls. Histology showed
      that adipocytes lose their lipid droplets under mechanical pressure; the expanded
      adipocytes have an elongated contour with a central nucleus. By the end of the
      expansion period, the thickness of the fat pads had decreased by 53%. One week
      after transplantation, expanded fat grafts had regained their previous volume
      with little sign of necrosis. Among normal adipocytes numerous smaller cells,
      containing multiple vacuoles, were seen. In contrast, about 25% of the substance
      of the non-expanded control fat graft consisted of necrotic oil cysts. These
      findings indicate that pre-expanded fat grafts survive better.

PMID- 7524987
TI  - The distribution of hyaluronan in human skin and mature, hypertrophic and keloid
      scars.
AB  - A hyaluronan-binding protein (HABP) was used to locate the distribution of HA in
      normal skin and in various types of scar tissue: mature scar tissue, hypertrophic
      scar tissue and keloids. The study was intended to establish whether or not a
      deviant HA distribution could explain the different clinical features of these
      scar tissues. The distribution of HA was found to differ between the various scar
      tissues. In normal skin an intense HA-staining was observed in the papillary
      dermis. In mature scar tissue the distribution of HA resembled that of normal
      uninjured tissue, but the layer of HA was thinner. In hypertrophic scar tissue,
      HA occurred mainly as a narrow strip in the papillary dermis. Keloid tissue
      showed the least HA-staining of the papillary layer and resembled that of the
      bulging reticular dermis. In contrast, the thickened granular and spinous layer
      of the keloid epidermis exhibited an intense HA-staining. We suggest that the
      altered distribution and amount of HA in these different scar tissues may
      contribute to their different clinical characteristics. This histochemical
      technique for the demonstration of HA in scar tissue could be of use in clinical
      work to decide on therapeutic strategies.

PMID- 7524988
TI  - The use of morphine in surgery: an overview.

PMID- 7524989
TI  - The differential effects of felodipine and nitrendipine on cerebral
      dihydropyridine binding ex vivo and the ethanol withdrawal syndrome in mice.
AB  - 1. The ability of two dihydropyridine calcium channel antagonists, felodipine and
      nitrendipine both to displace [3H]-isradipine binding in CNS tissue measured ex
      vivo and to protect against the ethanol withdrawal syndrome has been
      investigated. 2. Mice were injected with various doses of felodipine or
      nitrendipine and [3H]-isradipine binding measured in brain homogenates prepared
      0.5, 3 or 5 h later. Inhibition versus dose curves were sigmoid and the dose
      required to produce 50% inhibition increased linearly with time after
      administration. Felodipine was approximately 10 times more potent than
      nitrendipine. 3. Nitrendipine (50 mg kg-1, i.p.) and felodipine (10 mg kg-1,
      i.p.) produced around a 75% inhibition of [3H]-isradipine binding 3 h later.
      Binding of [3H]-nitrendipine to cerebral tissues measured after in vivo injection
      of the ligand was decreased by nitrendipine (50 mg kg-1) and felodipine (10 mg kg
      1) to a similar extent. 4. Nitrendipine (50 mg kg-1) prevented the behavioural
      signs of ethanol withdrawal as measured by handling induced convulsions, but
      felodipine (10 mg kg-1 or 2 mg kg-1) did not provide any protection against this
      effect of ethanol withdrawal. Felodipine (10 mg kg-1, twice daily) during the
      course of ethanol treatment also failed to attenuate the withdrawal syndrome. 5.
      The convulsive response to a mild audiogenic stimulus during ethanol withdrawal
      was increased following one dose of felodipine (5 mg kg-1, i.p.) but unaffected
      by nitrendipine. 6. Injection of Bay K 8644 (60 microgram, i.c.v.) produced a
      significant increase in handling-induced convulsive behaviour. Felodipine (10 mg
      kg-1, i.p.) reduced this behaviour both 60 and 120 min later, while nitrendipine
      (50 mg kg-1) showed a modest reduction only at 120 min.7. In contrast,
      nitrendipine (50mg kg-1) and felodipine (10 mg kg-1) produced similar effects on
      the hyperexcitability produced by handling following administration of
      bicuculline. Hexamethonium(8 mg kg-1) had no effect on this response.8. No change
      was found in [3H]-isradipine or [125I]-w-conotoxin binding to cerebral tissue
      prepared from ethanol-dependent mice.9. These results demonstrate that while
      felodipine and nitrendipine have similar actions on some CNS-mediated effects
      (raising seizure thresholds to several convulsant drugs), felodipine, in contrast
      to nitrendipine, has no effect on the ethanol withdrawal syndrome. Suggested
      explanations for the results include the possibility that nitrendipine may
      protect against the ethanol withdrawal syndrome via sites other than
      dihydropyridine receptors: that felodipine has partial agonist actions at
      dihydropyridine receptors in the CNS or that felodipine has actions which mask
      its protective effect in ethanol withdrawal.

PMID- 7524990
TI  - Down-regulation of bombesin binding to guinea-pig pancreatic acinar cells during
      homologous desensitization.
AB  - 1. [125I]-Tyr4-bombesin exhibited saturable binding to pancreatic acinar cells.
      2. Preincubation of cells at 37 degrees C with 0.03 nM-1 microM-bombesin for 10
      min followed by acid or neutral washes reduced subsequent binding of [125I]-Tyr4
      bombesin in a concentration-dependent manner by up to 90%. 3. In cell
      suspensions, bombesin raised the cytoplasmic Ca2+ concentration ([Ca2+]i) and the
      [Ca2+]i response was reduced by pre-exposure to the agonist. 4. In individual
      superfused cells, bombesin at 1 nM normally caused a large [Ca2+]i transient
      followed by sustained [Ca2+]i oscillations. The cells exhibited a variable degree
      of desensitization when subsequently exposed to higher agonist concentrations. 5.
      Preincubation with bombesin for 10 min caused a concentration-related reduction
      of subsequent amylase responses to bombesin. 6. Down-regulation of receptor
      binding is a rapid phenomenon during bombesin exposure explaining, at least
      partially, tachyphylaxis of [Ca2+]i and amylase responses.

PMID- 7524992
TI  - Potentiation by forskolin of both SNP- and ANP-stimulated cyclic GMP accumulation
      in porcine isolated palmar lateral vein.
AB  - 1. The aim of this study was to examine the effect of modulation of adenosine
      3':5'-cyclic monophosphate (cyclic AMP) levels (by using forskolin, a direct
      activator of adenylyl cyclase, or rolipram, a cyclic AMP selective
      phosphodiesterase inhibitor) on basal and stimulated guanosine 3':5'-cyclic
      monophosphate (cyclic GMP) levels in the porcine isolated palmer lateral vein by
      use of a [3H]-guanine prelabelling technique. 2. Sodium nitroprusside (SNP; 10(
      5) - 10(-3) M) and atrial natriuretic peptide (ANP; 10(-8) - 10(-6) M), produced
      concentration-dependent increases in [3H]-cyclic GMP levels via stimulation of
      soluble and particulate guanylyl cyclase respectively. The SNP-stimulated [3H]
      cyclic GMP response peaked after 5 min in the presence and absence of the
      phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). 3. In the
      absence of IBMX, forskolin (3 x 10(-5) M) significantly increased [3H]-cyclic GMP
      levels to 118.5 +/- 8.7% of basal values (P < 0.05, n = 8), and significantly
      increased both the SNP- and ANP-stimulated [3H]-cyclic GMP accumulation at all
      concentrations of SNP and ANP used. For example, effects at the maximal SNP (10(
      3) M) and ANP (10(-6) M) concentrations were: SNP: 154.7 +/- 15.4% of basal;
      SNP+forskolin: 191.3 +/- 14.8% of basal (P < 0.05, n = 4); ANP: 161.4 +/- 17.4%
      of basal; ANP+forskolin: 220.0 +/- 20.0% of basal (P < 0.05, n = 4). 4. The
      cyclic AMP-selective phosphodiesterase inhibitor, rolipram (10-5 M), had no
      effect on basal or SNP-stimulated [3H]-cyclic GMP levels; however, the
      combination of forskolin and rolipram produced an increase in the basal (158.7 +/
      27.1% of basal) and SNP-stimulated [3H]-cyclic GMP accumulation(SNP (10-3 M):
      165.3 +/- 8.7% of basal; SNP + forskolin + rolipram: 510.7 +/- 64.8% of basal;
      P<0.05,n = 5), greater than either forskolin or rolipram alone. The
      phosphodiesterase inhibitor, IBMX (10-3 M)significantly raised [3H]-cyclic GMP
      levels, and forskolin (3 x 10- M) in the presence of IBMX had no significant
      effect on either basal or SNP-stimulated [3H]-cyclic GMP levels (e.g. in the
      presence of IBMX: SNP (10-3 M): 660 +/- 90% of basal; SNP + forskolin: 790 +/-
      86% of basal, n = 3).5. The data indicate the presence of both soluble and
      particulate guanylyl cyclase in the porcine isolated palmar lateral vein. The
      ability of forskolin to potentiate SNP- and ANP-stimulated [3H]-cyclic GMP
      accumulation may suggest a cyclic AMP-cyclic GMP interaction at the level of the
      phosphodiesterases.Further, the ability of cyclic AMP to influence cyclic GMP
      levels may indicate that the two nucleotides, as well as having independent
      mechanisms to induce smooth muscle relaxation, could produce vasodilatation via a
      common mechanism.

PMID- 7524993
TI  - Cutaneous vasodilatation induced by nitric oxide-evoked stimulation of afferent
      nerves in the rat.
AB  - 1. The site of action at which nitric oxide (NO) may contribute to neurogenic
      vasodilatation in the hindpaw skin of urethane-anaesthetized rats was examined by
      the use of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO
      synthase. 2. Skin blood flow was measured by laser Doppler flowmetry, and
      neurogenic vasodilatation was evoked either by topical application of mustard oil
      (5%) or antidromic electrical stimulation of the saphenous nerve (antidromic
      vasodilatation). 3. L-NAME (60 mumol kg-1, i.v.) attenuated the hyperaemia evoked
      by mustard oil in an enantiomer-specific manner but failed to reduce antidromic
      vasodilatation and the vasodilatation due to i.v. injected calcitonin gene
      related peptide (CGRP) and substance P (0.1-1 nmol kg-1 each), two proposed
      mediators of neurogenic vasodilatation. 4. Pretreatment of rats with capsaicin
      (125 mg kg-1, s.c. 2 weeks beforehand), to defunctionalize afferent neurones,
      reduced the hyperaemic response to mustard oil and prevented L-NAME from further
      decreasing the vasodilatation evoked by mustard oil. 5. Intraplantar infusion of
      sodium nitroprusside (SNP, 0.15 nmol in 1 min), a donor of NO, induced hyperaemia
      which was significantly diminished by the CGRP antagonist CGRP8-37 (50 nmol kg-1,
      i.v.) and by capsaicin pretreatment. The ability of CGRP8-37 to inhibit the
      vasodilator response to SNP was lost in capsaicin-pretreated rats. 6. Taken
      together, these data indicate that NO does not play a vasorelaxant messenger role
      in neurogenic vasodilatation but can contribute to activation of, and/or
      transmitter release from, afferent nerve fibres in response to irritant
      chemicals.

PMID- 7524991
TI  - Comparative pharmacology of analogues of S-nitroso-N-acetyl-DL-penicillamine on
      human platelets.
AB  - 1. The effects of two new analogues of S-nitroso-N-acetyl-DL-penicillamine
      (SNAP), S-nitroso-N-formyl-DL-penicillamine (SNFP) and S-nitroso-DL-penicillamine
      (SNPL), on platelet function were examined in vitro. 2. SNAP and its analogues
      were potent inhibitors of platelet aggregation and inducers of disaggregation. 3.
      All compounds inhibited fibrinogen binding to platelets. 4. They also decreased
      the release of P-selectin from platelets. 5. Both inhibition of fibrinogen
      binding and release of P-selectin correlated with an increase in intraplatelet
      cyclic GMP concentrations. 6. At concentrations sufficient to inhibit platelet
      function and induce cyclic GMP formation (0.01-3 microM), the release of NO could
      be detected from SNPL but not from SNAP and SNFP. 7. Release of NO from all
      compounds was detected at concentrations > or = 10 microM. 8. Thus, the
      spontaneous release of NO from SNPL explains the actions of this compound on
      platelet function; however, platelet-mediated mechanisms may be involved in the
      release of NO from SNAP and SNFP.

PMID- 7524994
TI  - Strain-dependency of leukotriene C4 generation from isolated lungs of immunized
      mice.
AB  - 1. The antigen-induced leukotriene C4 (LTC4)-like-material release from isolated
      perfused lungs of actively sensitized Swiss, Balb/C and CBA/J mice was compared.
      The intra-tracheal (i.t.) instillation of 1 and 100 micrograms ovalbumin to lungs
      from Swiss mice was followed by a dose-dependent generation of LTC4-like material
      into the effluent, as detected by radio-immunoassay and h.p.l.c., followed by an
      enzyme-immunoassay. In contrast, lungs from sensitized Balb/C and CBA/J mice
      failed to exhibit LTC4-like-material release in amounts above the basal values.
      No histamine secretion was observed when lungs of the three strains of mice were
      challenged with ovalbumin. 2. The i.t. instillation of 1 or 10 micrograms
      platelet-activating factor (PAF) or of 100 micrograms arachidonic acid to lungs
      from non-sensitized mice, induced the release of comparable amounts of LTC4-like
      material in the effluent, irrespective to the strain. However, N-formyl-L
      methionyl-L-leucyl-L- phenylalanine (fMLP, 0.1, 10 micrograms), was more
      effective in inducing the release of LTC4-like-material from lung from Swiss and
      CBA, than from Balb/C, mice. 3. The intraplantar injection of 0.01 microgram
      ovalbumin to sensitized Swiss mice induced an intense oedema formation, as
      measured plethysmographically, while Balb/C mice required a dose of antigen at
      least 10 fold higher for a similar response. CBA/J mice did not respond to
      antigen challenge in terms of oedema formation. The intraplantar injection of PAF
      or fMLP to non-immunized mice induced an oedema of similar intensity in all the
      strains considered. Accordingly, the different responses to ovalbumin of the
      three strains of mice is not accounted for by different paw responsiveness to
      inflammatory mediators.4. Swiss and CBA/J mice exhibited higher titers of
      circulating IgG antibodies, as measured by passive cutaneous anaphylaxis (PCA),
      than Balb/C mice. Conversely, lower IgE titers were measured in the serum of
      sensitized Swiss and CBA/J mice, as compared to Balb/C.5. Our results demonstrate
      a strain-dependency of antigen-induced LTC4 release from lungs from sensitized
      mice. This difference is related to the ability of sensitized animals to develop
      immediate hypersensitivity responses, such as paw oedema formation, but not to
      the antibody subclass involved in the immunization. Strain-dependent factors may
      influence the intensity of the response to antigen stimulation. It is thus
      essential to characterize the different components of the immune response when
      mouse models for studying hypersensitivity reactions are developed.

PMID- 7524996
TI  - Evaluation of the smoke-free Olympics project.

PMID- 7524995
TI  - Landscapes: complex optimization problems and biopolymer structures.
AB  - The evolution of RNA molecules in replication assays, viroids and RNA viruses can
      be viewed as an adaptation process on a 'fitness' landscape. The dynamics of
      evolution is hence tightly linked to the structure of the underlying landscape.
      Global features of landscapes can be described by statistical measures like
      number of optima, lengths of walks and correlation functions. The evolution of a
      quasispecies on such landscapes exhibits three dynamical regimes depending on the
      replication fidelity: Above the "localization threshold" the population is
      centered around a (local) optimum. Between localization and "dispersion
      threshold" the population is still centered around a consensus sequence, which,
      however, changes in time. For very large mutation rates the population spreads in
      sequence space like a gas. The critical mutation rates separating the three
      domains depend strongly on characteristics properties of the fitness landscapes.
      Statistical characteristics of RNA landscapes are accessible by mathematical
      analysis and computer calculations on the level of secondary structures: these
      RNA landscapes belong to the same class as well known optimization problems and
      simple spin glass models. The notion of a landscape is extended to combinatory
      maps, thereby allowing for a direct statistical investigation of the sequence
      structure relationships of RNA at the level of secondary structures. Frequencies
      of structures are highly non-uniform: we find relatively few common and many rare
      ones, as expressed by a generalized form of Zipf's law. Using an algorithm for
      inverse folding we show that sequences sharing the same structure are distributed
      randomly over sequence space. Together with calculations of structure
      correlations and a survey of neutral mutations this provides convincing evidence
      that RNA landscapes are as simple as they could possibly be for evolutionary
      adaptation: Any desired secondary structure can be found close to an arbitrary
      initial sequence and at the same time almost all bases can be substituted
      sequentially without ever changing the shape of the molecule. Consequences of
      these results for evolutionary optimization, the early stages of life, and
      molecular biotechnology are discussed.

PMID- 7524997
TI  - Total transurethral resection versus minimal transurethral resection of the
      prostate--a 10-year follow-up study of urinary symptoms, uroflowmetry and
      residual volume.
AB  - OBJECTIVE: To assess the long-term results of total transurethral resection (T
      TURP) and minimal transurethral resection of the prostate (M-TURP) in patients
      with obstructive symptoms caused by benign prostatic hyperplasia. PATIENTS AND
      METHODS: Between September 1979 and September 1980, 167 patients were studied: 83
      were randomized to T-TURP and 84 to M-TURP. The patients were examined pre
      operatively and 6 and 12 months post-operatively. Ten years post-operatively they
      were invited to attend for further examination, including uroflowmetry,
      determination of residual volume and evaluation of subjective symptoms. RESULTS:
      At the 10-year follow-up 39 patients were found to have died and 47 were lost to
      follow-up. Twelve patients had undergone repeat TURP and seven had been treated
      for urethral stricture. Thus 33 T-TURP and 29 M-TURP patients underwent detailed
      examination. Significant relief in obstructive and irritative symptoms was seen
      in both groups. The improvement in maximum flow rate remained stable throughout
      the follow-up period, with no significant differences between the two groups.
      Post-void residual urine decreased throughout follow-up, with minor differences
      between the groups. CONCLUSION: M-TURP is recommended as an alternative to T
      TURP.

PMID- 7524998
TI  - Prostate specific antigen as a predictor of an abnormal digital rectal
      examination.
AB  - OBJECTIVE: To assess the ability of serum prostate specific antigen (PSA) to
      predict and differentiate patients with normal and abnormal digital rectal
      findings. SUBJECTS AND METHODS: A prospective analysis of 1374 participants in a
      prostate cancer screening programme was performed. After completion of a
      questionnaire including age and voiding symptoms as well as phlebotomy for PSA
      analysis, digital rectal examination was performed and the findings were
      categorized with respect to size, consistency, symmetry and nodularity. RESULTS:
      In men less than 50 years of age the mean serum PSA level failed to discriminate
      any of the digital rectal examination categories. In men over 50 there was a
      statistically significant difference in mean PSA levels between symmetrical,
      normal sized prostates and symmetrically enlarged glands as well as between
      symmetrical, normal sized and abnormal prostates (P < 0.05). No statistically
      significant difference was found in mean serum PSA levels between symmetrically
      enlarged prostate glands and those with palpable nodules. PSA levels < or = 2.5
      ng/ml (normal range for the Yang polyclonal assay) and < 7.4 ng/ml (corresponding
      to the normal range of < 4.0 ng/ml for the Hybritech monoclonal assay)
      demonstrated a probability of an abnormal digital rectal examination of 11% and
      14% respectively. PSA levels > 18.4 ng/ml (corresponding to monoclonal levels of
      > 10 ng/ml) had a 67% probability of an abnormal digital rectal examination.
      However, moderate elevations in PSA could not be used to predict digital
      examination abnormalities due to the high incidence of moderate PSA elevations
      associated with symmetrical enlargement of the prostate. CONCLUSIONS: Serial
      annual PSA measurements may provide an alternative means of screening men over 50
      years of age. Contamination of results with PSA elevation due to benign prostatic
      hyperplasia remains, however, a problem.

PMID- 7524999
TI  - Quality of life after palliative radiotherapy in patients with hormone-resistant
      prostate cancer: single institution experience.
AB  - OBJECTIVE: To review the development, methodology and difficulties of evaluating
      the quality of life (QoL) in patients with hormone-resistant prostate cancer, and
      to analyse the subjective effect of palliative radiotherapy among these patients.
      PATIENTS AND METHODS: Since 1986, a self-administered QoL questionnaire has been
      developed for patients with hormone-resistant prostate cancer. The study group
      included 137 such patients, with a median age of 70 years (range 48-87), who
      received either 89Sr (31) or external beam radiotherapy (106) because of painful
      bone metastases. Quality of life was assessed in all patients before treatment
      and, if possible, 3 months afterwards. RESULTS: The questionnaire had acceptable
      psychometric properties (validity, reliability). In these patients with very
      advanced disease, palliative radiotherapy proved less effective than reports in
      the literature might suggest. CONCLUSIONS: In patients with hormone-resistant
      prostate cancer, quality of life assessment is both possible and desirable for
      the evaluation of palliative treatment. The patients' perception of physical
      function represents an independent prognostic factor of overall survival together
      with alkaline phosphatase and performance status. Valid and reliable QoL
      questionnaires are now available, though further research is required to
      establish the most effective way of using them. At 3 months palliative
      radiotherapy was effective in only 25% of the patients investigated, two-thirds
      of whom had > or = 20 hot spots on bone scan. Palliative radiotherapy should
      probably be offered during an earlier phase of the disease.

PMID- 7525000
TI  - Agonist-like activity of anti-peptide antibodies directed against an autoimmune
      epitope on the heart muscarinic acetylcholine receptor.
AB  - A synthetic peptide corresponding to amino acids 169-193 of the second
      extracellular loop of the M2 human muscarinic receptor was used to raise
      antibodies in rabbits. Affinity purified antibodies specifically recognized a
      major band with a molecular weight of about 80 kDa on the electrotransferred
      membrane proteins of both rat ventricles and chinese hamster ovary cells
      expressing recombinant muscarinic receptors. Incubation of these antibodies with
      rat myocardial membranes resulted not only in a decrease in the maximal binding
      capacity, but also in a decrease in receptor antagonist affinity. These
      antibodies could also mimic the effects of agonist stimulation as demonstrated by
      inhibition of isoproterenol-stimulated cAMP accumulation and by a negative
      chronotropic effect on cultured cardiomyocytes. These results suggest that the
      second extracellular loop of the M2 muscarinic receptor is an immunologically and
      functionally important domain with properties comparable to those found for
      autoantibodies against the same domain in idiopathic dilated cardiomyopathy. It
      strengthens the hypothesis that the second extracellular loop of the members of
      the superfamily of G-protein coupled membrane receptors could be the main
      immunogenic region responsible for a pathogenic autoimmune response.

PMID- 7525001
TI  - Cloning of a putative inhibitory amino acid receptor subunit from the parasitic
      nematode Haemonchus contortus.
AB  - A cDNA, HGl, encoding an inhibitory amino-acid receptor subunit has been cloned
      from a mixed egg population of the parasitic nematode Haemonchus contortus. The
      predicted amino-acid sequence of the subunit shows 24% to 32% homology with other
      vertebrate and invertebrate GABAA and glycine receptor subunits and has all the
      expected motifs for a member of the ligand-gated ion channel superfamily. When
      expressed in Xenopus oocytes HGl gives a small response to 1 mM glycine, but not
      to 1 mM GABA, glutamate, taurine or L-alanine.

PMID- 7525003
TI  - The burning of the New World: the extent and significance of broadcast burning by
      early humans.
AB  - It is possible to delimit the areas of the North, Central, and South America that
      are most susceptible to fire and would have been most affected by burning
      practices of early Americans. Areas amounting to approximately 155 x 10(5) km2
      are here designated as the most burnable part of the New World. Using estimates
      of burnable biomass, burning frequency, and burning efficiency, the authors
      determine the amount of biomass burned annually in an environment in which
      anthropogenic fires were at a hypothesized maximum. The amount of carbon released
      annually approximates estimates for present-day burning. Changes in carbon sinks
      may have been the most significant aspect of a shift to a low-biomass state.
      Decreases in stored biomass, soil carbon, and charcoal production may have had
      effects on a global scale. Likewise, the shift to a higher biomass/lower fire
      frequency state over the last 400-500 years may be one component of an increased
      mid- to high-latitude carbon sink. The assessment made here is preliminary but
      may aid in clarifying the state of the climate system during the pre-industrial
      period.

PMID- 7525002
TI  - Angiotensin AT2 receptor mediated inhibition of particulate guanylate cyclase: a
      link with protein tyrosine phosphatase stimulation?
AB  - Ever since the identification of two distinct Ang II receptor subtypes, the
      function of the AT2 receptor has been a subject of debate. As opposed to the AT1
      subtype, this receptor does not interact with G-proteins in most cell lines and
      tissues. We show here that, in intact PC12W cells which express only AT2
      receptors, Ang II significantly decreases basal and atrial natriuretic peptide
      (ANP)-stimulated cGMP concentration. This effect is mimicked by the AT2 selective
      agonist CGP 42112, and is not prevented by the AT1 selective antagonist losartan,
      indicating that this is an AT2 receptor mediated response. The lack of effect of
      the phosphodiesterase (PDE) inhibitor IBMX shows that this mechanism does not
      involve PDE stimulation. This is confirmed by the finding that neither Ang II or
      CGP 42112 affect the Ca++/calmodulin dependent cGMP PDE activity. Furthermore Ang
      II and CGP 42112 have no effect on nitroprusside-stimulated cGMP levels in these
      cells, thus ruling out interactions between the AT2 receptor and soluble
      guanylate cyclase. These data indicate that the AT2 receptor mediated decrease of
      cGMP is due to the selective inhibition of particulate guanylate cyclase (pGC)
      activity. In an accompanying paper we report that interaction of Ang II with the
      AT2 receptor in the same cells results in the stimulation of phosphotyrosine
      phosphatase (PTPase) activity. Interestingly, the PTPase inhibitors sodium
      orthovanadate and phenylarsine oxyde, but not the Ser/Thr phosphatase inhibitor
      okadiac acid, inhibitthe Ang II and CGP 42112 induced decreases in cellular cGMP
      concentration. These findings suggest that stimulation of PTPase activity may be
      involved in the regulation of pGC activity via AT2 receptors.

PMID- 7525004
TI  - Enantioselective degradation of alpha-hexachlorocyclohexane and cyclodiene
      insecticides in roe-deer liver samples from different regions of Germany.
AB  - Remarkably high concentrations of alpha-hexachlorocyclohexane (alpha-HCH), cis
      heptachlorepoxide and oxychlordane were found in roe-deer liver samples both from
      the northern and southern German states Schleswig-Holstein and Baden-Wurttemberg,
      respectively. The data revealed no significant regional differences, but they
      showed some common characteristics: a preferential degradation of (+)-alpha-HCH,
      and a preferential enrichment of (+)-oxychlordane and of (+)-cis
      heptachlorepoxide as determined by chiral capillary gas chromatography using
      modified cyclodextrin phases. Calculation of the spearman rank correlation
      coefficients rS supported the assumption that higher concentrations of alpha-HCH
      may result in a stronger decomposition of the (+)-enantiomer, while higher levels
      of cis-heptachlorepoxide and oxychlordane appear to lead to a faster
      decomposition of the respective (-)-enantiomer or a preferential formation of the
      respective (+)-enantiomer.

PMID- 7525005
TI  - Human genetics. What is good about cystic fibrosis?
AB  - The remarkably high level of cystic fibrosis mutations among Caucasians may be
      due to a reduction in heterozygotes in the severity of the diarrhea caused by
      enterotoxic bacteria.

PMID- 7525006
TI  - Conduction abnormalities are restricted to the central nervous system in
      experimental autoimmune encephalomyelitis induced by inoculation with proteolipid
      protein but not with myelin basic protein.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating
      disease of the central nervous system (CNS) and can be induced by inoculation of
      animals with homogenized CNS tissue or highly purified myelin proteins such as
      myelin basic protein (MBP) or proteolipid protein (PLP). It is widely studied as
      a possible animal model of multiple sclerosis. We performed the present
      neurophysiological study to define the location of nerve conduction abnormalities
      in EAE induced by immunization with PLP (PLP-EAE) and in EAE induced by
      immunization with MBP (MBP-EAE) in the Lewis rat. In rats with tail weakness due
      to acute PLP-EAE, conduction was normal in the spinal nerve roots and peripheral
      nerves but there was evidence of conduction block in a high proportion of the
      fibres in the dorsal columns of the lumbosacral spinal cord. In contrast, in
      acute MBP-EAE, there was conduction block in a high proportion of fibres in the
      sacral dorsal and ventral roots of the peripheral nervous system (PNS) and in the
      dorsal columns of the lumbosacral spinal cord. The distribution of nerve
      conduction abnormalities is consistent with previous histological studies showing
      that inflammation and primary demyelination are restricted to the CNS in PLP-EAE,
      but are present in the CNS and in the spinal roots of the PNS in MBP-EAE. The
      restriction of functional abnormalities to the CNS in PLP-EAE but not in MBP-EAE
      may have implications for the human inflammatory demyelinating diseases,
      including multiple sclerosis.

PMID- 7525007
TI  - Three distinct subpopulations of GABAergic neurons in rat frontal agranular
      cortex.
AB  - GABAergic interneurons in the rat frontal cortex were subdivided on the basis of
      immunoreactivity for calcium binding proteins, neuropeptides and nitric oxide
      synthase, using double immunofluorescence and mirror image immunohistochemical
      methods. The results indicate that in this region of the neocortex there are at
      least three distinct subpopulations of local circuit neurons. The first subgroup
      consists of parvalbumin-immunoreactive cells. Those do not contain neuropeptide,
      calretinin or nitric oxide synthase immunoreactivity. A substantial number of
      parvalbumin-immunoreactive cells in layer II/III were also immunoreactive for
      calbindin D28k. The second subgroup consists of cells immunoreactive for
      calretinin. Most were usually immunoreactive for vasoactive intestinal
      polypeptide as well, but a few cells in layer II/III were immunoreactive for one
      or the other only. Calretinin-immunoreactive cells do not colocalize parvalbumin,
      somatostatin or nitric oxide synthase, and only a few colocalize calbindin D28k.
      The third subgroup consists of cells most of which contain somatostatin, and is
      entirely separate from the parvalbumin- and calretinin-immunoreactive
      populations. There was substantial colocalization of somatostatin and calbindin
      D28k and of somatostatin and neuropeptide Y. Some somatostatin-immunoreactive
      cells showed nitric oxide synthase immunoreactivity. All of the populations of
      immunoreactive cells examined in the present study also showed GABA
      immunoreactivity. About 10% of calbindin D28k-immunoreactive cells and all of
      those strongly stained for calbindin D28k in layer II/III showed GABA
      immunoreactivity. Most calbindin D28k-positive cells in deep layers also showed
      GABA immunoreactivity. These results support that almost all calbindin D28k
      immunoreactive non-pyramidal cells are probably GABAergic.

PMID- 7525009
TI  - Inhibition of the 5-HT3 receptor-mediated current by the protein kinase
      inhibitor, H-7.
AB  - The effect of the protein kinase inhibitor, H-7, on the inward current mediated
      by 5-HT3 receptors was investigated with the whole-cell patch-clamp technique. H
      7 inhibited the peak 5-HT current with an IC50 of 1.79 microM. The inhibition was
      quick, reversible and not blocked by the presence of 50 microM intracellular H-7.
      It is concluded that the effect of H-7 was independent of protein kinase
      activity.

PMID- 7525010
TI  - Differential antinociceptive effects of sendide, a NK1-receptor antagonist, and
      morphine in the capsaicin test.
AB  - The peptide NK1-receptor antagonists, sendide and [D-Trp7]sendide, have been
      evaluated for antinociceptive activity in the capsaicin test. Both peptides,
      injected intrathecally (i.t.) 5 min prior to intraplantar capsaicin, produced a
      dose-dependent reduction of the capsaicin-induced paw licking response. Naloxone
      (4.0 mg/kg) pretreatment did not affect sendide- and [D-Trp7]sendide-induced
      antinociception, whereas naloxone at a dose of 0.5 mg/kg antagonized the
      antinociceptive effect of i.t. administered morphine. Conversely, the
      antinociceptive action induced by both NK1-receptor antagonists was reduced
      significantly by i.t. co-administration of substance P. Morphine-induced
      antinociception was not antagonized by co-administration of substance P. These
      results led us to the understanding of differential action mechanism of NK1
      receptor antagonist- and morphine-induced antinociception as assayed by the
      capsaicin test.

PMID- 7525008
TI  - NMDA and carbachol but not AMPA affect differently the release of [3H]GABA in
      striosome- and matrix-enriched areas of the rat striatum.
AB  - The effects of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA; 10(-3)
      M), N-methyl-D-aspartate (10(-3) M, in the absence of magnesium or presence of
      AMPA) and carbachol (10(-3) M) on the release of preloaded [3H]gamma-aminobutyric
      acid ([3H]GABA) from microdiscs of tissue punched out from sagittal brain slices
      in striosome- or matrix-enriched areas of the rat striatum have been compared.
      Although AMPA stimulated similarly the release of [3H]GABA in both striatal
      compartments, the release of [3H]GABA evoked by either N-methyl-D-aspartate (in
      the presence of AMPA) or carbachol was more pronounced in matrix- than in
      striosome-enriched areas. AMPA- and N-methyl-D-aspartate- (in the absence of
      magnesium) evoked responses were reduced but not abolished in the presence of
      tetrodotoxin (10(-6) M) in both compartments while the carbachol-evoked release
      of [3H]GABA was decreased by tetrodotoxin only in the matrix. The interruption of
      cholinergic transmission by the combined application of atropine (10(-5) M) and
      pempidine (10(-4) M) was without effect on the AMPA-evoked release of [3H]GABA,
      but it reduced the N-methyl-D-aspartate- (in the absence of magnesium or presence
      of AMPA) evoked release of [3H]GABA in both compartments, these reductions being
      of similar amplitude than those observed with tetrodotoxin.

PMID- 7525011
TI  - Complete cerebral ischemia with short-term survival in rats induced by cardiac
      arrest. I. Extracellular accumulation of Alzheimer's beta-amyloid protein
      precursor in the brain.
AB  - The distribution of beta-amyloid protein precursor (APP) was investigated
      immunocytochemically in rats subjected to global cerebral ischemia (GCI) induced
      by cardiac arrest. Rats underwent 10 min of GCI with 3, 6, and 12 h and 2 and 7
      days of survival. APP immunostaining was found extracellular and intracellularly.
      Multiple extracellular APP immunoreactive deposits around and close to the
      vessels appeared as soon as 3 h after GCI. Extracellular accumulation of APP
      occurred frequently in the hippocampus, cerebral and cerebellar cortex, basal
      ganglia and thalamus and rarely in the brain stem. These deposits were labelled
      with antibodies against the N-terminal, beta-amyloid peptide, and C-terminal
      domains of APP. Our data suggests that either proteolytically cleaved fragments
      of the full-length APP or the entire APP molecule accumulates extracellularly
      after GCI. This findings may not only implicate the participation of APP in
      postischemic tissue damage but also suggest the involvement of pathomechanisms
      operating in ischemia in Alzheimer's disease pathology.

PMID- 7525013
TI  - NADPH-diaphorase histochemistry and nitric oxide synthase activity in
      deutocerebrum of the crayfish, Pacifastacus leniusculus (Crustacea, Decapoda).
AB  - The activity of an nitric oxide synthase in the deutocerebrum of the crayfish
      Pacifastacus leniusculus was investigated with histochemical and biochemical
      methods. By using the NADPH-diaphorase histochemical reaction, known as a
      selective marker for NO synthase in mammals, it was possible to localize specific
      neuronal elements in the crayfish. Pronounced diaphorase-staining was observed in
      peripheral olfactory sensory cells and in the neuropil of the olfactory lobes.
      Less intense diaphorase-staining also occurred in other deutocerebral neuropils,
      such as the accessory lobes, the lateral antennular neuropil and in the
      deutocerebral commissure neuropil. The biochemical assay revealed a
      calcium/calmodulin-dependent formation of citrulline from L-arginine in brain
      homogenate. It was also possible to show that the selective NO synthase inhibitor
      L-NOARG decreased the formation of citrulline. These data indicate a role for NO
      as an intercellular messenger in the crayfish.

PMID- 7525012
TI  - Inhibition of endogenous dopamine release in amphibian retina by L-2-amino-4
      phosphonobutyric acid (L-AP4) and trans-2-aminocyclopentane-1,3-dicarboxylate
      (ACPD).
AB  - The metabotropic glutamate receptor agonists 2-amino-4-phosphonobutyric acid
      (AP4) and trans-2-aminocyclopentane-1,3-dicarboxylate (ACPD) blocked light
      stimulated dopamine release from Xenopus laevis retina. ACPD suppressed release
      in darkness but AP4 did not. AP4 blocked release stimulated in darkness by
      picrotoxin, a GABA-A receptor antagonist. The data suggest that regulation of
      dopamine release in Xenopus retina involves subpopulations of metabotropic
      glutamate receptors.

PMID- 7525014
TI  - Short-term fluoxetine treatment alters monoamine levels and turnover in discrete
      brain nuclei.
AB  - The effects of short-term fluoxetine administration on monoamine levels and
      turnover were assessed in discrete brain nuclei. Adult male rats received
      fluoxetine HCl (10 mg/kg) or saline injections intraperitoneally for 4 days and
      monoamine levels determined by high performance liquid chromatography. The major
      metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), was decreased by
      fluoxetine treatment in the ventromedial hypothalamic nucleus (VMN), the lateral
      hypothalamic area and the CA1 region of the hippocampus. Fluoxetine treatment
      significantly increased serotonin (5-HT) levels in the VMN but did not change 5
      HT levels in any other area examined. Norepinephrine (NE) levels were higher in
      fluoxetine-treated rats in the dorsomedial hypothalamic nucleus, dorsal raphe
      nucleus and parietal motor cortex (MCTX). 5-HT and NE turnover were also
      determined by the pargyline method. Fluoxetine treatment decreased 5-HT turnover
      in the VMN and increased 5-HT turnover in the median raphe. NE turnover was
      decreased in the preoptic area, the MCTX and parietal sensory cortex by
      fluoxetine administration. These results demonstrate that brain areas with
      similar 5-HT innervation respond differently to fluoxetine administration and
      fluoxetine, which selectively alters 5-HT uptake, also affects NE levels and
      turnover in several brain nuclei.

PMID- 7525016
TI  - Upregulation of nitric oxide synthase and galanin message-associated peptide in
      hypothalamic magnocellular neurons after hypophysectomy. Immunohistochemical and
      in situ hybridization studies.
AB  - The expression of several bioactive molecules in magnocellular hypothalamic
      neurons is modified when the axons of these cells are transected. In this study
      we have evaluated by means of immunocytochemistry and in situ hybridization the
      effect of hypophysectomy on the expression of nitric oxide synthase (NOS)- and of
      galanin message-associated peptide (GMAP)-like immunoreactivities (-LIs) as well
      as on their respective mRNAs in hypothalamic magnocellular neurosecretory
      neurons. The results show a transient increase in NOS- and GMAP-LIs in
      magnocellular neurons of both the paraventricular and supraoptic nuclei when
      compared to normal animals. The maximal increase in staining was observed between
      5 and 7 days, and by 14 days NOS-LI was back to normal levels, whereas strong
      GMAP-LI could still be detected in a few cells. A similar picture was observed
      for the NOS and GMAP mRNAs. The functional significance of the present findings
      is unclear, but they indicate a possible role of nitric oxide and GMAP in
      neurosecretory neurons after injury.

PMID- 7525015
TI  - Antagonism by forskolin of the 5-HT3 receptor-mediated current in nodose ganglion
      neurons is independent of cyclic AMP.
AB  - The effect of forskolin on the inward current mediated by 5-HT3 receptors (5-HT
      current) was investigated in rat nodose ganglion neurons. Forskolin inhibited the
      peak amplitude of the 5-HT current and increased current desensitization in a
      dose-dependent manner. Dideoxyforskolin, which does not stimulate adenylate
      cyclase, had a similar inhibitory effect on the 5-HT current. The effect of
      forskolin was neither mimicked by intracellular application of exogenous cyclic
      AMP (0.5 to 4 mM) nor occluded by intracellular forskolin (30 microM) or protein
      kinase inhibitor H-7 (100 microM). Intracellular applications of forskolin,
      cyclic AMP or H-7 had no effect on 5-HT current. Data suggest that forskolin
      acted at an extracellular site on 5-HT3 receptors and this effect of forskolin
      was not mediated by cyclic AMP-dependent processes.

PMID- 7525017
TI  - The intercellular communication via nitric oxide and its regulation in coupling
      of cyclic GMP synthesis upon stimulation of muscarinic cholinergic receptors in
      rat superior cervical sympathetic ganglia.
AB  - Cyclic GMP (cGMP) production in rat superior cervical sympathetic ganglia (SCG)
      was markedly increased (ca. 7-9-fold) by the addition of either acetylcholine
      (ACh; 0.1 mM) or a muscarinic agonist, carbachol (Carb; 0.1 mM), in the presence
      of an inhibitor (3-isobutyl-1-methylxanthine) for cGMP hydrolytic enzyme during
      in vitro aerobic incubation at 37 degrees C for 5 min. The ACh-induced
      accumulation of cGMP in SCG was effectively blocked (-73%) by the further
      addition of atropine (10 microM), a muscarinic antagonist, whereas a nicotinic
      blocker, hexamethonium (10 microM) partially antagonized (-41%) this ACh
      stimulation. The inhibitory effect of hexamethonium on ACh-evoked ganglionic cGMP
      production was effectively augmented (-83%) by addition of NG-monomethyl-L
      arginine (L-NMMA, 50 microM), a compound that inhibits nitric oxide (NO)
      synthesis from L-arginine. Comparable inhibition of cGMP formation was observed
      following application of L-NMMA to the SCG upon stimulation of Carb. In contrast,
      L-NMMA had no effect on the decreased level of ACh-evoked cGMP production caused
      by the muscarinic antagonist. The Carb-induced elevation of ganglionic cGMP
      synthesis was significantly reduced within 1 min of incubation in the medium
      containing hemoglobin (Hb; 20 microM), an agent that scavenges only the
      extracellular fraction of NO. Thereafter, the tissue cGMP formation attenuated to
      the control level by subsequent incubation for several minutes. Addition of
      protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol 13-acetate (TPA; 1
      microM) to the medium significantly decreased Carb-evoked cGMP synthesis (-61%)
      in SCG, whereas superoxide dismutase (SOD; 30 U/ml) only slightly suppressed the
      Carb stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525018
TI  - Analgesic and reinforcing effects of morphine in mice. Influence of Bay K-8644
      and nimodipine.
AB  - The aim of the present work was to clarify the role of calcium influx through L
      type calcium channels in the rewarding and analgesic effects of morphine.
      Therefore the effects of Bay K-8644 and nimodipine, dihydropyridine calcium
      agonist and antagonist, respectively, on the analgesic and rewarding effects of
      morphine in mice were studied. Morphine-induced analgesia was measured with the
      aid of writhing test, hot plate test and tail clip test. The rewarding properties
      of morphine were studied using i.v. self-administration in drug-naive mice. Bay K
      8644 potentiated morphine-induced analgesia in all the tests. The influence of
      nimodipine on morphine analgesia was more complicated and depended on the dose of
      morphine and test used. In self-administration experiments morphine exhibited the
      bell-shaped concentration-response curve. Bay K-8644 produced a shift of the
      curve to the left, while nimodipine had the opposite action indicating,
      respectively, facilitating and inhibitory influence on morphine rewarding effect.
      It is concluded that nimodipine exhibits partial antagonistic properties towards
      the rewarding action of morphine and slightly potentiates morphine-induced
      analgesia while Bay K-8644 increases either the rewarding or the analgesic
      effects of morphine.

PMID- 7525020
TI  - Ca2+ ionophore-induced apoptosis on cultured embryonic rat cortical neurons.
AB  - The neurotoxicity of ionomycin, a Ca2+ ionophore, was investigated in cultured
      cortical neurons from embryonic rats. While about 90% of neurons survived 2 h
      after exposure to ionomycin, the surviving neurons had decreased by about 30 to
      40% at 16 h. Both RNA and protein synthesis inhibitors blocked this
      neurotoxicity. Furthermore, c-Fos immunoreactive neurons increased not only in
      number but also in the intensity of immunoreactivity. These results suggest that
      ionomycin-induced neuronal cell death is an active process which requires de novo
      transcription and translation. In addition, the ultrastructural changes, such as
      shrinkage of cell body, compaction of nucleus, condensation of chromatin, and
      membrane blebbing, were observed by electron microscopy. These morphological
      changes are indexes of apoptosis. Furthermore, DNA fragmentation, a biochemical
      marker of apoptosis, was also observed. All the results suggest that ionomycin
      induced neuronal cell death is apoptotic.

PMID- 7525019
TI  - Galanin-containing axons synapse on tyrosine hydroxylase-immunoreactive neurons
      in the hypothalamic arcuate nucleus of the rat.
AB  - Prolactin (PRL) secretion by the anterior pituitary gland is dependent upon the
      tonic inhibitory influence of the tuberoinfundibular dopaminergic (TIDA) neuronal
      system. TIDA neurons, in turn, are regulated by various afferent neuronal
      systems. To support the concept that the recently-discovered neuropeptide,
      galanin (GAL), is one of the neurotransmitter/neuromodulator substances which
      might synaptically regulate the function of the TIDA system, immunocytochemical
      double-labeling studies were carried out in the hypothalamic arcuate nucleus (AN)
      of the male rat. The analysis of light microscopic preparations revealed the
      overlapping of GALergic and dopaminergic (detected by tyrosine hydroxylase
      immunoreactivity) neuronal elements in both the dorsomedial and ventrolateral
      parts of the AN. TH-containing perikarya and dendrites were contacted by varicose
      GAL-IR axons in these regions. The electron microscopic studies of ultrathin
      sections demonstrated axosomatic and axodendritic synapses between GALergic axons
      and TH-IR neurons. These findings support the view that GAL may modulate PRL
      release, acting as a neurotransmitter/neuromodulator in synaptic afferents to the
      TIDA system.

PMID- 7525022
TI  - Transendothelial electrical potential across pial vessels in anaesthetised rats:
      a study of ion permeability and transport at the blood-brain barrier.
AB  - Brain pial microvessels have previously been demonstrated to have blood-brain
      barrier properties. The potential difference (PD) across exposed brain pial
      microvessels, 20-60 microns in diameter and superfused with artificial CSF, has
      been measured in anaesthetised rats using glass microelectrodes. The PD on
      insertion into venous vessels, V(in), was 3.2 mV lumen negative, and in arterial
      vessels it was higher at 4.5 mV. Superfusion with high K(+)-CSF, made by
      replacing Na+ with K+, caused a positive deflection in PD, VK+, whereas reducing
      the Na+ alone, by replacing Na+ by Tris-HCl, made the lumen more negative. These
      two effects were additive. Studies on venous vessels showed that ouabain had no
      effect on V(in) and only affected VK+ under conditions of low Na pre-exposure.
      Neither histamine nor cimetidine had any effect on V(in) or VK+ whereas
      tetraethylammonium, a K(+)-channel blocker, reduced VK+ by 20%. These experiments
      demonstrate that changes in PD caused by changing abluminal Na+ or K+ are due
      predominantly to movement of ions through channels in the endothelial cell
      membranes, and that actions that alter the activity of the Na+,K(+)-ATPase or
      reduce the resistance of the paracellular pathway in parallel with increased
      membrane permeability have less effect on the PD.

PMID- 7525023
TI  - Expression of the complement membrane attack complex and its inhibitors in Pick
      disease brain.
AB  - The immunohistochemical localization of the complement membrane attack complex
      (MAC) was examined in Pick disease brain and compared with the distribution of
      three of its inhibitors, vitronectin, protectin and clusterin. Pick bodies were
      stained intensely for both the MAC and protectin, weakly for vitronectin, but
      negatively for clusterin. However, the clusterin antibody intensely stained some
      pyramidal neurons in affected cortical areas, including ballooned neurons. The
      present study indicates that a complement-mediated attack is associated with the
      formation of Pick bodies, and provides further suggestive evidence that clusterin
      may be a marker for active neuronal degeneration.

PMID- 7525021
TI  - Induction of NADPH-diaphorase activity in the hippocampus in a rat model of
      cerebral ischemia and ischemic tolerance.
AB  - Preconditioning of the brain with sublethal ischemia induces tolerance to
      subsequent lethal periods of ischemia (ischemic tolerance). In this study, we
      used NADPH-diaphorase histochemistry to investigate the postischemic changes of
      nitric oxide synthase (NOS) in the hippocampus in a rat model of cerebral
      ischemia and ischemic tolerance. Forebrain ischemia was induced by 4-vessel
      occlusion for 3 min as an ischemic preconditioning. Three days after the
      preconditioning or sham operation, second ischemia was induced for 6 min. A
      transient increase in NADPH-diaphorase activity, beginning after 2 h and maximal
      after 1 day, was observed in CA1 pyramidal neurons of rats subjected to 3 min of
      preconditioning ischemia as well as 6 min of subsequent ischemia both with and
      without preconditioning. In addition, expression of NADPH-diaphorase activity was
      seen in reactive glial cells in the damaged CA1 region of animals subjected to 6
      min of ischemia without preconditioning. Thus, direct involvement of increased
      NADPH-diaphorase activity in ischemic tolerance was not suggested because the
      increased NADPH-diaphorase activity preceded the induction of ischemic tolerance
      which takes place 1-7 days after preconditioning. However, the present findings
      suggest that the induction of neuronal NADPH-diaphorase activity occurs in
      response to cerebral ischemia.

PMID- 7525026
TI  - Catecholaminergic projections from the solitary tract nucleus to the perifornical
      hypothalamus.
AB  - The source of adrenergic and other catecholaminergic fibers innervating the
      perifornical lateral hypothalamus was localized in the medulla after combination
      of Fluoro-Gold retrograde tracing and immunohistochemistry for either tyrosine
      hydroxylase or phenylethanolamine-N-methyltransferase. Following perifornical
      injections, Fluoro-Gold-labeled neurons were observed mainly in regions including
      the noradrenergic and adrenergic cell groups. In the caudal solitary tract
      nucleus, two kinds of doubly labeled neurons were found: a) numerous
      noradrenergic neurons in the A2 group at the level of, or caudal to the area
      postrema; b) some adrenergic neurons in the C2 group at a level immediately
      rostral to the area postrema. These catecholaminergic neurons connecting the
      caudal solitary tract nucleus to the perifornical hypothalamus might convey
      feeding relevant information such as glycemic level or satiety signals.

PMID- 7525024
TI  - Autonomic and sensory cardiovascular activities of nonivamide: intrathecal
      administration of clonidine.
AB  - The effects of nonivamide on the cardiovascular system were examined and compared
      with the effects of substance P (SP) in rats. Intravenous (i.v.) injection (10
      micrograms/kg) of nonivamide produced triphasic pressure responses (A; depressor,
      B; pressor, and C; depressor) and biphasic bradycardia responses (f; fast
      bradycardia and s; slow bradycardia). IA injection (10 micrograms/kg) into the
      epigastric artery caused hypotension and mild tachycardia. The effects of
      atropine, vagotomy, SP antagonist, propranolol, and clonidine on these responses
      were examined and mechanisms responsible for the nonivamide-induced responses are
      postulated as follows. A and f are due to vagal reflex resulting from the
      excitation of afferent sensory neurons in the heart and are parasympathetic
      efferent effects from the nucleus solitarius. B is involved in sympathetic
      activation, partly caused by the release of SP in the spinal cord. C is due to
      the vasodilatory effect of SP released from perivascular stores. s was diminished
      by vagotomy and is due to the bradycardiac effect of acetylcholine, released by
      SP, from cardiac stores. The activation of the autonomic system is inhibited by
      clonidine and involved in the wide spectrum of nonivamide-induced cardiovascular
      effects.

PMID- 7525025
TI  - Serotonergic systems in brain and blood under stress and tranylcypromine
      treatment in rats.
AB  - The effects of stress on serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindole-3
      acetic acid (5-HIAA), and/or tryptophan in whole blood and various brain areas of
      rats pretreated with tranylcypromine were studied. In the whole blood,
      tranylcypromine given alone caused a rise in levels of 5-HT and a fall in levels
      of its metabolite (5-HIAA) and the ratio of 5-HIAA:5-HT, whereas in stressed rats
      pretreated with tranylcypromine only the last two findings were observed. We
      found that animals given tranylcypromine and subjected to water-immersion
      restraint stress exhibited the greatest rise in 5-HT levels in midbrain,
      hippocampus, and hypothalamus, together with the lowest 5-HIAA:5-HT ratio
      relative to controls, whereas in cortex, cerebellum, medulla, and striatum the
      highest levels of 5-HT together with the lowest ratio of 5-HIAA:5-HT were
      observed after the administration of tranylcypromine alone. 5-HT levels were
      found to be higher in medulla and striatum in rats given tranylcypromine alone
      relative to stressed rats pretreated with this drug. We concluded that regional
      differences account for variable effects of tranylcypromine on blood and brain
      serotonergic systems in vivo.

PMID- 7525027
TI  - Effects of dietary supplementation of beta 2-adrenergic agonist clenbuterol on
      carcase characteristics and some metabolites in ducks.
AB  - 1. Ducks (622 in total) aged 25 d were given diets supplemented with clenbuterol
      (CL) at 0 (control), 0.5, 1, 2, 3 and 5 mg/kg for 25 d to investigate the effect
      of dietary CL on muscle and fat deposition and some metabolites in ducks. 2. The
      mass of the breast muscles was increased by 10 to 31%, while subcutaneous fat
      plus skin and abdominal fat pad were reduced by 8 to 23% and 20 to 37%,
      respectively, in the ducks supplemented 1 to 5 mg CL/kg diet. 3. Increased
      RNA:DNA ratios in the breast muscle, reduced uric acid and increased free fatty
      acid concentrations in the serum were observed in clenbuterol-fed ducks.

PMID- 7525028
TI  - [Pathological basis for elevation of serum prostate specific antigen].
AB  - 67 patients with serum prostate specific antigen (PSA) over 4ng/ml were
      investigated pathologically. All the patients had prostatic lesions: prostate
      cancer (24) and benign prostatic lesions (43). The serum PSA was conspicuously
      higher in the carcinoma group than in the benign group (P < 0.01). When 10ng/ml
      was used as the low limit to detect prostate cancer, the sensitivity and
      specificity were 83.3% and 74.4% respectively. We suggest that the range of serum
      PSA from 4.0 to 10.0ng/ml should be considered dangerous in detecting prostate
      cancer. The epithelium-blood barrier lesion and epithelial hyperplasia of the
      prostate might be the pathological basis for the elevation of serum PSA.

PMID- 7525031
TI  - Cation fluxes and cation channels in outer segment membranes of bovine retinal
      rods: contamination by antibiotics applied to cattle?
AB  - Membrane vesicles were prepared from intact rod outer segments (ROSs) isolated
      from bovine retinas and were examined for the presence of cation-selective
      conductances. We performed macroscopic flux measurements in an ensemble of ROS
      membrane vesicles and single-channel measurements after fusion of ROS membrane
      vesicles with planar bilayer membranes. Two K(+)-permeable conductances were
      observed, the well-established cyclic GMP (cGMP) gated channel and an apparently
      new K+ channel with some unusual properties. Flux and single-channel data showed
      that the new conductance passed K+, Rb+, and Cs+ equally well but was much less
      permeable to Na+, Li+ and protons. Single-channel measurements revealed a linear
      current-voltage relationship and three unitary conductance states of 15, 11, and
      8 pS, using symmetric 150 mM KCl solutions. Measured macroscopic K+ fluxes varied
      considerably among different preparations, suggesting some unknown regulation of
      the channel; the variability appeared to arise from variation in the channel's
      open probability, not the unit conductance or the number of channels present. The
      recorded single-channel events and the selectivity data are remarkably similar to
      those reported for antibiotic channel-forming ionophore gramicidin. We believe
      that the variability in both macroscopic permeability experiments and single
      channel experiments may reflect a variable contamination with gramicidin applied
      to the animals as the topical antibiotic V-Sporin.

PMID- 7525033
TI  - Canada must be cautious about MD-assisted death, work to improve palliative care:
      CMA.

PMID- 7525029
TI  - Serum c-erbB-2 oncoprotein in the diagnosis of gastric cancer in comparison with
      CA 19-9, CEA, TPA, CA 125 and AFP.
AB  - BACKGROUND: Although many tumor markers can detect gastric cancer, they are still
      far from perfect. The aim of this study was to evaluate the role of a new tumor
      marker, serum c-erbB-2 oncoprotein, in patients with gastric cancer. METHODS: We
      tested this tumor marker in 35 patients of gastric cancer, 13 patients of
      hepatoma, 13 patients of colon cancer, 8 patients of lung cancer, and 22 patients
      without malignancy (4 of acute pancreatitis, 10 of benign gastric ulcer and 8
      normal subjects) between July and December 1991. A newly developed enzyme
      immunoassay kit was used to assay serum c-erbB-2 oncoprotein. RESULTS: Abnormal
      level of c-erbB-2 oncoprotein was found in 11/32 (34.4%) of gastric cancer, 4/13
      (30.8%) of hepatoma, 2/8 (25%) of lung cancer, 3/13 (23.1%) of colon cancer, 0/3
      (0%) of gastric lymphoma, and 4 of non-malignant conditions (18.2%). Six tumor
      markers were assessed at the same time in 32 patients of gastric cancer. The
      abnormal level for CA 19-9 was found in 13/32 patients (40.6%); for TPA: 9/32
      (28.1%); for c-erbB-2 oncoprotein: 11/32 (34.4%); for CEA: 8/32 (25%); for CA
      125: 2/32 (6.3%); and for AFP: 1/32 (3.1%). CONCLUSIONS: C-erbB-2 oncoprotein is
      a new tumor marker. Practical application needs further mass survey.

PMID- 7525030
TI  - Angiotensin II induced alteration of cyclic adenosine 3',5'-monophosphate
      generation in the hypertrophic myocardium of Dahl salt-sensitive rat on a high
      salt diet.
AB  - The objective of this study was to explore the action of angiotensin II (AII) on
      cardiac contractility and cyclic AMP (cAMP) generation by forskolin and
      isoproterenol in the hypertrophic myocardium of the salt-sensitive Dahl rat.
      Inbred Dahl S and Dahl R rats that had been on a diet supplemented with 6% NaCl
      were studied. The functional effects of the interaction of AII and forskolin on
      cardiac contractility were assessed in the isolated heart preparation. The effect
      on the cAMP signal transduction pathway was assessed in cardiomyocytes isolated
      from hearts of Dahl S and R rats. Dahl S rats developed cardiac hypertrophy on a
      high-salt diet, whereas Dahl R rats did not. Forskolin increased cardiac
      contractility, which was differently affected by AII, depending on whether the
      heart was from hypertrophied Dahl S rat or from the control Dahl R rat. AII
      accentuated forskolin-induced increases in cardiac contractility in hypertrophic
      hearts but diminished forskolin-induced increases in contractility in the
      nonhypertrophied hearts. This response was reflected in the cAMP response to
      forskolin, in that AII decreased forskolin-induced increases in cAMP in the
      nonhypertrophic heart. AII had the reverse effect in cardiomyocytes from
      hypertrophied hearts, as AII increased forskolin-induced cAMP production. This
      was shown to be due to an AII receptor mediated effect, as it was antagonized by
      the AII receptor antagonist saralasin. The same effects of AII were found on
      isoproterenol-induced increases in cAMP. Similar results occurred in the presence
      of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), suggesting
      that the effect was on cAMP production rather than cAMP degradation. This was
      attributed to an inhibitory G protein (Gi) mechanism, as the muscarinic agonist
      carbachol, which acts through Gi, produced the same effects as AII. Furthermore,
      the effects of AII were abolished by pertussis toxin, which inactivates Gi. These
      data indicate a reversal of control by AII in the hypertrophic Dahl S heart in
      response to forskolin, which activates adenylyl cyclase directly on the catalytic
      subunit, converting the substrate, ATP, to cAMP, independent of the guanine
      nucleotide activated protein, and in response to isoproterenol, which activates
      adenylyl cyclase through G protein mechanisms. All accentuated the forskolin
      induced increase in cardiac contractility and cAMP generation in the
      hypertrophied ventricle but decreased both contractility and cAMP generation in
      nonhypertrophied hearts, suggesting that the process of cardiac hypertrophy in
      salt-sensitive Dahl rat may compensate for the reduction in intracellular cAMP by
      altering its regulatory control by AII.

PMID- 7525032
TI  - Substance P activates Cl- and K+ conductances in guinea-pig tracheal smooth
      muscle cells.
AB  - Substance P (SP) causes bronchoconstriction, but its effects on airway smooth
      muscle ion conductances are unknown. We investigated the effects of SP on single
      smooth muscle cells dissociated from guinea-pig trachealis. Under voltage clamp
      at -60 mV, SP evoked reversible contractions and inward current (ISP). ISP had a
      latency of approximately 1 s, reached a peak of 1039 +/- 147 pA (n = 19) about 2
      s after onset of application, and declined to baseline levels over the next 5-10
      s. At more positive holding potentials (-25 and 0 mV), the inward current was
      decreased in magnitude and preceded by outward current. With 140 mM K+ in the
      electrode and Cl- equilibrium potential (ECl) of about 0 mV, ISP was outwardly
      rectifying and reversed at -11 +/- 2 mV. When K+ currents were blocked using Cs+,
      the current-voltage relationship for ISP was linear and reversed at 3 +/- 1 mV.
      The reversal potential was dependent on the Cl- gradient across the membrane.
      These results suggest that SP caused a transient activation of Cl- and K+
      conductances. Following the initial transient inward current, SP caused a
      prolonged suppression of spontaneously active K+ currents. The findings that SP
      evoked contractions during voltage clamp at potentials at which voltage-dependent
      Ca2+ channels are not active, and that current oscillations were also evoked by
      SP, suggest that SP is acting through release of Ca2+ from internal stores.
      Furthermore, SP occluded the inward current evoked by acetylcholine, suggesting
      that the peptidergic and cholinergic signalling pathways converge.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7525035
TI  - Serum-soluble interleukin-2 receptor concentrations in patients with gastric
      cancer.
AB  - BACKGROUND: Serum concentrations of soluble interleukin-2 receptor (IL-2R) were
      found to be high in patients with autoimmune diseases, lung cancer, malignant
      lymphoma, tuberculosis, and other diseases. Serum-soluble IL-2R was evaluated as
      a tumor maker in patients with gastric cancer. METHODS: Preoperative
      concentrations of serum-soluble IL-2R were examined in 40 patients with gastric
      cancer. The authors investigated the correlations of serum-soluble IL-2R
      concentrations with various characteristics of this cancer (disease stage, gross
      appearance, depth of the tumor, lymph node metastasis, liver metastasis,
      peritoneal metastasis, histopathologic grade, serum carcinoembryonic antigen
      (CEA), alpha-fetoprotein (alpha-FTP), carbohydrate antigen 19-9 (CA19-9), and
      immunosuppressive acidic protein (IAP). Serum soluble IL-2R concentrations were
      measured with an enzyme-linked immunosorbent assay. RESULTS: Levels of serum
      soluble IL-2R in patients with gastric cancer were significantly higher than
      those of normal control subjects. Serum concentrations of IL-2R in patients with
      lymph node metastasis were also significantly higher than those of patients
      without lymph node metastasis. There were no significant differences in
      histopathologic findings (grade, lymphatic invasion, venous invasion). Moreover,
      serum concentrations of soluble IL-2R in patients who were IAP positive were
      significantly higher than those who were IAP negative. CONCLUSIONS: Preoperative
      serum-soluble IL-2R concentrations in patients with gastric cancer reflect the
      occurrence of regional lymph node metastases. Preoperative evaluation of serum
      soluble IL-2R concentrations may be a valuable parameter of indicating the
      probability of lymph node metastasis preoperatively.

PMID- 7525036
TI  - Serum des-gamma-carboxyprothrombin concentration determined by the avidin-biotin
      complex method in small hepatocellular carcinomas.
AB  - BACKGROUND: Des-gamma-carboxyprothrombin (DCP) is a useful tumor marker for
      hepatocellular carcinoma (HCC). The present method for measurement of DCP
      concentration, however, does not have adequate sensitivity to detect small HCCs.
      METHODS: The serum DCP concentration was investigated by the avidin-biotin
      complex (ABC) method in patients with an HCC smaller than 20 mm in maximum
      dimension. A serum DCP concentration greater than 4.0 arbitrary units per liter
      using the ABC method was considered abnormal. RESULTS: Of 115 patients with small
      HCC, 45 (39.1%) had an abnormal DCP concentration. Ten of 141 patients with
      chronic hepatitis (7.1%), 18 of 115 (15.7%) with cirrhosis, and 0 of 30 normal
      control patients had abnormal DCP concentrations. This method yielded a
      sensitivity of 39.1%, a specificity of 89.1%, a positive predictive value of
      61.6%, and a negative predictive value of 76.5% for detection of small HCC. The
      detectability of HCC increased to 56.5% when alpha-fetoprotein (AFP) was was
      measured (> 40 ng/ml). Abnormal DCP concentrations were seen in 8 of 34 (23.5%),
      24 of 42 (57.1%), and 5 of 7 (71.4%) patients with Edmondson's Grade I, II, and
      III tumors, respectively. There was a significant relationship between DCP
      concentrations and histologic grade (P = 0.0017), but there was no association
      between DCP concentration and other patient characteristics. Elevation of serum
      AFP concentrations in patients with hepatitis B surface antigen positivity,
      however, was more frequent than that in patients who were antihepatitis C virus
      (HCV) positive. Therefore, the measurement of serum DCP concentrations may be
      more useful than that of serum AFP concentrations in patients with anti-HCV
      positivity. CONCLUSIONS: The measurement of serum DCP concentrations by the ABC
      method is a useful diagnostic tool for the monitoring of small HCC.

PMID- 7525034
TI  - Connective tissue alterations in systemic sclerosis.

PMID- 7525037
TI  - Delta-T-lymphocytosis in a patient with thymoma.
AB  - BACKGROUND: Malignant thymoma is composed of neoplastic epithelial cells and
      small lymphocytes. Rarely, patients also may have peripheral T-lymphocytosis.
      These lymphocytes have been considered nonneoplastic because of their microscopic
      appearance and immunophenotype, as well as gene rearrangement studies. METHODS: A
      42-year-old man developed lymphocytosis 3 years after the completion of intensive
      combined chemoradiotherapy protocol for lymphocytic thymoma. These peripheral
      blood lymphocytes were evaluated phenotypically and genotypically. RESULTS:
      Immunophenotyping established that the cells were CD3 positive, CD4 negative, CD8
      negative, T-cell receptor (TCR)-alpha/beta negative, and TCR-gamma/delta
      positive. Gene rearrangement studies with TCR-delta probe confirmed the
      monoclonality of these cells. Chromosome analysis showed deletion of chromosome
      Y. The clinical course was progressive and had the features of malignant
      lymphoma. CONCLUSIONS: To the authors' knowledge, this is the first report of a
      patient with thymoma in whom monoclonal proliferation of T-gamma/delta peripheral
      blood lymphocytes was confirmed immunophenotypically and genotypically. These
      monoclonal TCR-gamma/delta lymphocytes may belong to the malignant clone of the
      thymoma; however, the possibility that they represent an evolution of a second
      lymphatic malignancy cannot be excluded.

PMID- 7525039
TI  - Recurrent ovarian cancer. Effective radiotherapeutic palliation after
      chemotherapy failure.
AB  - BACKGROUND: Recurrent ovarian cancer after frontline chemotherapy is incurable;
      however, palliation of focal lesions often is needed to alleviate symptoms.
      Because published response rates to palliative irradiation (RT) among patients
      failing cisplatin-based chemotherapy are scarce, the authors attempted to define
      the palliative role of radiotherapy for symptomatic, localized ovarian cancer
      recurrences. Factors predicting a response to RT also were sought. METHODS:
      Between 1987 and 1993, 33 patients with ovarian cancer were irradiated at 47
      sites with palliative intent after failing cisplatin-based chemotherapy regimens.
      Sites irradiated included the pelvis (n = 33), abdomen (n = 5), chest (n = 4),
      brain (n = 3), and other (n = 2). Median RT dose was 35 Gy (range: 7.5-45 Gy).
      The median fraction size was 2.5 Gy (range, 1-5 Gy). To determine dose
      effectiveness, the biologic effective dose (BED) was calculated according to the
      following formula: BED = total dose (1 + fractional dose/alpha/beta) using an
      alpha/beta value of 10. The median BED10 was 44 (range, 9-72). RESULTS: For the
      entire group, complete palliative response was 51% and overall palliative
      response was 79%. The median duration of palliation was 4 months, which reflected
      palliation until death in 90% of cases. The overall response rates by symptoms
      were: pulmonary symptom relief in 75%, vaginal bleeding control in 90%, rectal
      bleeding control in 85%, pain relief in 83%, and neurologic symptoms controlled
      in 50%. The likelihood of obtaining complete symptomatic response was
      significantly increased among those with high Karnofsky performance status (KPS >
      or = 70 vs. KPS < 70; 69% vs. 36%, P < 0.03) and among those who received a
      higher biologically effective dose of irradiation (BED10 > or = 44 vs. BED10 <
      44; 68% vs 35%, P < 0.03). Complete palliative response rates were not influenced
      by histologic differentiation, the number of previously administered cisplatin
      regimens, or patient age. Treatment-related acute morbidities included diarrhea
      in 5 of 38 (13%) patients treated through abdominal or pelvic fields, and
      esophagitis in 2 of 5 treated through thoracic portals. Only one severe late
      morbidity (small bowel obstruction) was observed. CONCLUSIONS: Durable palliation
      of patients with ovarian cancer that recurs after cisplatin-based chemotherapy
      can be achieved with local radiotherapy, especially among patients with high
      performance status. Biologically effective doses of at least 44 Gy10 (e.g., 3500
      cGy/14 fractions = BED10 of 44) should be sought to maximize the probability of
      complete response. Such dose-fractionation schedules can be delivered
      expeditiously with acceptable tolerance. These results are comparable to the
      published experience of second-line chemotherapy in the treatment of focally
      symptomatic ovarian cancer recurrences.

PMID- 7525038
TI  - Intravenous pamidronate disodium treatment of bone metastases in patients with
      breast cancer. A dose-seeking study.
AB  - BACKGROUND: Treatment of the symptoms of bone metastases currently involves the
      use of narcotic medication, radiation therapy, or hormonal therapy. Pamidronate
      disodium, a bisphosphonate, may prove helpful in the palliative treatment of bone
      metastases in patients with breast cancer as demonstrated in this multicenter,
      dose-ranging trial. METHODS: Ambulatory female patients age 18 years or older
      with breast cancer metastatic to bone and a life expectancy of at least 3 months
      were eligible for the study. Bone metastases were confirmed by bone scan or bone
      survey within 6 months of enrollment. Sixty-one patients were treated as
      outpatients and were randomized to receive one of four intravenous pamidronate
      regimens for 12 weeks: 30 mg administered every 2 weeks, 60 mg every 4 weeks, 60
      mg every 2 weeks, or 90 mg every 4 weeks. The primary efficacy parameter for this
      study was pain score. The change from baseline in pain score was determined for
      each patient at each study visit and at endpoint, defined as the last
      postbaseline evaluation for each patient before or at week 12. Secondary efficacy
      variables included narcotic scores, urinary calcium/creatinine and
      hydroxyproline/creatinine ratios, serum osteocalcin and bone alkaline phosphatase
      concentrations, and bone lesion (radiologic) response. RESULTS: At 3 months, the
      regimens of 60 mg every 4 weeks, 60 mg every 2 weeks, and 90 mg every 4 weeks
      resulted in significant reduction in bone pain beginning by week 6 of treatment.
      The regimen of 30 mg every 2 weeks was not effective. Narcotic use, as reflected
      by narcotic scores, did not parallel the pain scores, because there was little
      evidence of any effect for any of the treatment groups. Reduction in bone pain
      was accompanied by decreases in urinary calcium/creatinine and
      hydroxyproline/creatinine ratios, and bone alkaline phosphatase concentrations.
      Side effects of pamidronate were mild and transient. Radiographic changes
      consistent with healing of lytic lesions were observed in 15 patients (25%).
      CONCLUSION: Intravenous pamidronate is a well tolerated treatment that produced
      significant relief of bone pain in the majority of patients with metastatic
      breast cancer at the three highest doses tested.

PMID- 7525040
TI  - The use of prostate specific antigen density to improve the sensitivity of
      prostate specific antigen in detecting prostate carcinoma.
AB  - BACKGROUND: Prostate specific antigen (PSA) is useful as a tumor marker for
      monitoring patients with prostate cancer after definitive therapy. Limitations
      have been noted when PSA was used for the early detection of prostate cancer. The
      use of prostate specific antigen density [PSAD = PSA (ng/ml)/prostate volume
      (cc)] has been suggested to differentiate benign from malignant prostate disease.
      METHODS: A retrospective analysis of 559 men who underwent transrectal prostate
      ultrasound and biopsy for an abnormal PSA value (> 4.0 ng/ml) and/or an abnormal
      prostate gland by digital rectal examination (DRE) was performed. Prostate
      specific antigen density evaluation was performed on all men, and its utility for
      diagnosing prostate cancer was compared with those of PSA and DRE. RESULTS: Two
      hundred, sixty seven (47%) of the 559 men had positive biopsies for prostate
      cancer. Sixty-one men had PSA levels of less than 4.0 ng/ml, and 17 (27.8%) of
      these men had positive biopsies for prostate cancer. No patient with a normal DRE
      had a positive biopsy regardless of the prostate specific antigen density (PSAD)
      value. PSAD was not more useful than PSA alone in detecting prostate cancer in
      this group. Two hundred, seventy-seven men had PSA values between 4.1 and 10.0
      ng/ml, and 110 (40.0%) had positive biopsies for prostate cancer. For this group
      as a whole, the mean PSA values of the positive and negative biopsy groups showed
      no significant difference. The mean PSAD was significantly different (P < 0.0001)
      between the positive and negative biopsy groups. Two hundred, twenty-one men had
      PSA values of greater than 10.0 ng/ml, and 140 (63%) had positive biopsies for
      prostate cancer. Prostate specific antigen density was no more useful than PSA
      alone in distinguishing men with positive or negative biopsies for prostate
      cancer in the entire group. In the subset of patients with a normal DRE,
      (including no benign prostatic hyperplasia) the mean PSAD appeared useful (P <
      0.004) in distinguishing the positive from the negative biopsy groups, whereas
      the mean PSA was not. CONCLUSION: These results suggest that PSAD is useful in
      discriminating prostate cancer in men with normal DRE and PSA levels between 4.1
      and 10.0 ng/ml.

PMID- 7525041
TI  - Prostate specific antigen density in patients with histologically proven prostate
      carcinoma.
AB  - BACKGROUND: Prostate specific antigen (PSA) does not appear to have the
      specificity to distinguish between benign prostate hyperplasia and cancer when
      the PSA is low. PSA density is thought by many to improve the specificity for
      cancer; however, this theory remains controversial. METHODS: The authors
      retrospectively reviewed 220 carcinomas in radical prostatectomy specimens and
      examined the relationship of PSA and PSA density to prostate volume, Gleason sum,
      and pathologic stage. RESULTS: Prostate specific antigen and PSA density parallel
      each other and do not appear to correlate statistically with displaced volume of
      the prostate, Gleason sum, or pathologic stage. However, PSA density in the PSA
      4.1-10 ng/ml group may have conferred unique information secondary to increased
      variation in prostate volume. Furthermore, PSA density was associated more than
      PSA with carcinoma in the PSA < or = 4.0 ng/ml group. A PSA density cutoff of
      greater than 0.05 ng/ml/ml was accurate in the diagnosis of 94.9% of the patients
      with cancer. Finally, carcinomas with a Gleason sum of greater than 6 in patients
      with a PSA density of greater than 0.3 ng/ml/ml had a high probability of being
      extra-capsular at the time of surgery. CONCLUSIONS: Although PSA and PSA density
      appear to mirror each other in many ways, PSA density confers unique information
      and may be used as an adjunct to PSA and digital rectal examination in the
      detection and staging of prostate cancer. If prostate needle biopsy is performed,
      PSA density and Gleason sum may help identify patients who are at high risk for
      surgical failure.

PMID- 7525043
TI  - Nucleolar organizer regions in lining epithelium adjacent to squamous cell
      carcinoma of human oral mucosa.

PMID- 7525044
TI  - Dermatofibroma: superficial fibrous proliferation with reactive histiocytes--a
      multiple immunostaining analysis.

PMID- 7525042
TI  - The cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, and
      procarbazine (COPBLAM-I) regimen for intermediate-grade non-Hodgkin's lymphoma.
      Long term follow-up in 51 patients.
AB  - BACKGROUND: Cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin,
      and procarbazine (COPBLAM-I) is a second generation combination chemotherapy for
      intermediate-grade non-Hodgkin's lymphoma (NHL). Since the first report by
      Laurence et al. in 1982, only a few series were reported on the long term results
      of this regimen. METHODS: In this prospective study, the clinical courses of 51
      patients with intermediate-grade NHL (F, G, or H according to the International
      Working Formulation grading criteria) with a median age of 65 years (range, 55
      81), who were diagnosed between 1983 and 1992, are reported. Eligibility criteria
      included at least one full cycle of the regimen and no previous chemotherapy.
      RESULTS: A mean of seven cycles (range, two to nine) with two escalations (range,
      zero to six) was administered. In a median follow-up of 2.4 years (range, 0.5
      10), 33 patients (65%) experienced complete remission. The projected 3-year
      overall survival (OS) and progression free survival rates (PFS) were 58% and 77%,
      respectively, and the projected 5-year OS and PFS were 52% and 72%, respectively.
      In only 2 patients (4%) were treatment-related deaths observed, whereas nonfatal
      complications were more common. Patients in the low risk group, according to the
      international NHL prognostic index, had the best outcome. The mean percentage of
      projected dose intensity (DI) was 95% (range, 77-109), whereas no difference in
      DI was found between patients younger or older than 65 years. CONCLUSIONS: In a
      single center, COPBLAM-I combination chemotherapy was safe and effective for
      patients older than 55 years with intermediate-grade NHL.

PMID- 7525045
TI  - Treatment of aggressive non-Hodgkin' lymphomas. Lessons from the past 10 years.
AB  - Therapy for aggressive non-Hodgkin's lymphomas has undergone significant
      evolution in the last 25 years. First generation combination chemotherapy studies
      produced complete remissions (CRs) of 45-53%, with 30-37% long term survivors.
      New treatment programs aimed at increasing CR rates were then developed with the
      assumption that the additional complete responders would also become long term
      disease free survivors. Initial reports of single institution pilot studies with
      third generation regimens suggested 68-86% CR and 58-69% survival; however, with
      longer follow-up, the survival decreased. Furthermore, confirmatory national
      Phase II trials using these newer regimens produced CR rates of only 49-65% and
      survival of 50-61%. Thus conclusions concerning the efficacy of these new
      regimens awaited the results of prospective randomized trials. The Southwest
      Oncology Group (SWOG) recently conducted a randomized trial comparing standard
      therapy, CHOP, to the third generation chemotherapy regimens, m-BACOD, ProMACE
      CytaBOM, or MACOP-B. There is no difference in response rate, time to treatment
      failure, or overall survival between CHOP and the third generation regimens.
      However, the cost and toxicity levels of the new regimens were higher. Thus, CHOP
      remains the best available standard of care, but based on the finding that fewer
      than 50% of these patients are cured, SWOG believes that new treatment approaches
      for patients with advanced-stage aggressive histology non-Hodgkin's lymphoma must
      be developed.

PMID- 7525046
TI  - Three-dimensional modelling of tumor-induced ovarian angiogenesis.
AB  - It is now well established that unrestricted growth of tumors is dependent upon
      angiogenesis. However, previous studies on tumor growth have not yet revealed how
      the transition to an angiogenetic state in ovarian malignancy is reflected in the
      vascular architecture of the ovary. We report here our preliminary observations
      based upon three-dimensional imaging of normal and tumor-induced ovarian
      angiogenesis created with a computer-assisted three-dimensional interactive
      application. The findings suggest that tumor-induced angiogenesis creates a
      bizarre vascular architecture, with a possible link to chaotic behavior.

PMID- 7525048
TI  - Social and cultural dimensions of hair loss in women treated for breast cancer.
AB  - The chief goal of this exploratory study was to discover what a woman's own
      experience of her illness meant to her--how she thinks of herself as a woman and
      a person with a health problem. The study was exploratory in nature and designed
      to expand our conceptual thinking about health and illness and the delivery of
      health-care services. The study was qualitative, and the principal method was the
      semi-structured, indepth, face-to-face interview. All of the women in the study
      had been diagnosed with primary breast cancer and were in a variety of stages of
      treatment. What emerged from the study were explanatory stories that women
      constructed to chronicle their illness experience and interpret it. The theme
      under discussion here is hair loss as symbolic of larger cultural beliefs and
      values. Recommendations for interventions with women who experience hair loss as
      a traumatic event are offered in the context of a deeper cultural understanding
      of hair loss that is a consequence of cancer care.

PMID- 7525050
TI  - Prostatic localization of spontaneous early invasive carcinoma in Lobund-Wistar
      rats.
AB  - Animal models of human prostate cancer are very limited in number but are of
      obvious importance to develop. Dr. Morris Pollard (M. Pollard, J. Natl. Cancer
      Inst., 51: 1235-1241, 1973) has reported that Lobund-Wistar rats develop
      spontaneous metastatic prostatic cancer when they become old (approximately 25%
      incidence after 25 months). A chemically induced form of the disease has also
      been described in Lobund-Wistar rats. However, recent reports suggest that most
      of the chemically induced adenocarcinomas are not prostatic in origin, with most
      arising in the seminal vesicle, and thereby raise questions about the origin of
      the spontaneous cancers. We herein report cancer spontaneously arising in the
      lateral lobes of the prostates in Lobund-Wistar rats. One of 8 rats killed at 16
      months of age showed prostatic carcinoma in situ. Two of 39 rats killed at 20
      months displayed early invasive adenocarcinomas with no signs of metastases.
      Because sectioning of the prostates in this study was limited to face sections
      from a single block for each rat, it is highly probable that the true incidence
      of dysplasias and carcinomas is underestimated by these data. Dysplastic or
      neoplastic changes were not seen in either the seminal vesicles or other portions
      of the prostatic complex. The nuclei of adenocarcinoma cells showed less labeling
      with antibody to the androgen hormone receptor than did normal cells. These data
      strongly support the validity of the Pollard model of spontaneous prostate cancer
      in Lobund-Wistar rats.

PMID- 7525047
TI  - Reversion of the transformed phenotypes of v-H-ras NIH3T3 cells by flavonoids
      through attenuating the content of phosphotyrosine.
AB  - Fifteen flavonoids were employed to examine their effects on the morphological
      changes, foci formation in soft agar and cellular growth in v-H-ras-transformed
      NIH3T3 cells. The data presented here demonstrated that only three specific
      flavonoids--apigenin, kaempferol, and genistein--exhibited the reverting effect
      on the transformed phenotypes of ras-3T3 cells. For example, treatment with 25
      microM of these flavonoids could effectively reverse the transformed morphology
      of ras-3T3 cells into flatter cells with contact inhibition. Colony formation in
      soft agar was decreased to 0.11%, 0.15%, and 0.35% by 25 microM apigenin,
      kaempferol, and genistein, respectively, as compared with control (0.92%). It was
      also found that the proliferation of ras-3T3 cells was significantly inhibited by
      these compounds in a dose-dependent manner. Finally, two biochemical parameters,
      the content of phosphotyrosine and cAMP, were examined to see whether affected by
      these compounds. The results showed the phosphotyrosine content in ras-3T3 cells
      was dramatically decreased by apigenin and kaempferol, but that was slightly
      reduced by genistein. By contrast, these three flavonoids all failed to
      significantly alter the level of cAMP within this transformant. Based on these
      observations, we suggest that some specific flavonoids are capable of reverting
      the transforming properties of v-H-ras transformed cells. The possible mechanism
      of this reversion is not mediated by activating the protein kinase A or its
      associated pathways, but rather inhibiting tyrosine kinases, subsequently leading
      to the blockage of p21ras-mediated signal transduction circuitry.

PMID- 7525049
TI  - Adoptive immunotherapy with murine tumor-specific T lymphocytes engineered to
      secrete interleukin 2.
AB  - Adoptive immunogene therapy of cancer is not widely studied, although it has been
      proposed as a promising strategy for cancer gene therapy. One of the major
      obstacles to this approach is the difficulty in introducing cytokine genes
      efficiently into T lymphocytes. In this report, we developed an adoptive
      immunotherapy model with murine tumor-specific cytotoxic T lymphocytes. By using
      an adenoviral vector, we achieved up to 100% gene transduction of murine T
      lymphocytes. Treatment of mice with the cytotoxic T lymphocytes genetically
      modified to produce interleukin 2 resulted in reduction of tumor metastasis and
      longer survival from intracerebral tumor death, providing a hopeful strategy for
      treatments of human cancers.

PMID- 7525052
TI  - CWR22: androgen-dependent xenograft model derived from a primary human prostatic
      carcinoma.
AB  - The long-term propagation of primary human prostate cancer (PCA) in vivo or in
      vitro has been rare. Most such PCAs are phenotypically different from most PCAs
      in humans; i.e., they make little prostate specific antigen and respond little,
      if at all, to androgen deprivation. A serially transplantable, primary human PCA,
      designated CWR22, exhibits a clonal cytogenetic aberration, causes high
      elevations of prostate specific antigen in the peripheral blood of nude mice, and
      is unusually responsive to androgen deprivation as compared with other
      xenografts. Studies of mRNA from CWR22 have demonstrated the expression of
      prostate specific antigen and the epidermal growth factor receptor family
      including erbB1/epidermal growth factor receptor, erbB2/neu, and erbB3, but not
      erbB4. A ligand for these receptors, the neu differentiation factor, is also
      expressed.

PMID- 7525053
TI  - Mammary fibroblasts may influence breast tumor angiogenesis via hypoxia-induced
      vascular endothelial growth factor up-regulation and protein expression.
AB  - Recent studies demonstrate the relationship of microvessel density to malignant
      progression in breast cancer (N. Weidner, J. P. Semple, W. R. Welch, and J.
      Folkman, N. Engl. J. Med., 324: 1-8, 1991), underscoring the importance of
      angiogenesis in this tumor. Crucial in tumor angiogenesis are the paracrine
      actions of tumor-secreted factors (e.g., vascular endothelial growth factor),
      which have been thought to derive from the tumor epithelial cells themselves. We
      demonstrate that in response to hypoxic conditions, human mammary fibroblasts
      dramatically up-regulate vascular endothelial growth factor mRNA and increase
      vascular endothelial growth factor protein levels in accordance with the degree
      of oxygen deprivation. Thus, mammary stromal cells, only recently considered in
      the regulation of breast carcinomas, may play a hitherto unrealized role in
      breast cancer angiogenesis.

PMID- 7525051
TI  - Autonomous growth in serum-free medium and production of hepatocellular
      carcinomas by differentiated hepatocyte lines that overexpress transforming
      growth factor alpha 1.
AB  - Transforming growth factor alpha (TGF-alpha) is a polypeptide closely associated
      with hepatocyte proliferation in vivo and in vitro. In order to investigate the
      mechanisms by which TGF-alpha contributes to hepatocyte replication and
      transformation, we isolated hepatocytes from mice bearing a human TGF-alpha
      transgene and examined their growth properties and gene expression in defined,
      serum-free culture. The transgenic hepatocytes continued to overexpress human TGF
      alpha mRNA and peptide, and were able to proliferate without exogenous growth
      factors in primary culture, in contrast to nontransgenic mouse hepatocytes. In
      short-term culture the transgenic hepatocytes underwent 1 wave of DNA replication
      at 72-96 h in culture before senescing, similar to nontransgenic hepatocytes
      supplemented with epidermal growth factor. Constitutive expression of TGF-alpha
      rendered the transgenic hepatocytes unresponsive to further growth stimulation by
      exogenous TGF-alpha, as well as other mitogens such as epidermal growth factor
      and hepatocyte growth factor. However, it did not alter their sensitivity to
      growth inhibition by TGF beta 1, 2 and 3. The addition of nicotinamide to the
      culture medium enabled both transgenic and epidermal growth factor-supplemented
      normal hepatocytes to replicate repeatedly and survive for > or = 2 months in
      primary culture while maintaining differentiated traits. From these long-term
      primary cultures of transgenic and nontransgenic hepatocytes, we established
      immortalized cell lines (designated TAMH and NMH lines, respectively). Both lines
      continued to express differentiated adult hepatocytic markers such as albumin,
      alpha-1-antitrypsin, transferrin, and connexin 26 and 32 mRNAs, but also
      expressed mRNAs for the oncofetal markers alpha-fetoprotein and insulin-like
      growth factor II. Unlike the near-diploid NMH hepatocyte line, the transgenic
      TAMH hepatocyte line was quasi-tetraploid, strongly expressed human TGF-alpha
      mRNA, and was highly tumorigenic in nude mice. Well-differentiated hepatocellular
      carcinomas developed in nude mice given injections of the TAMH line, and these
      appeared similar to the primary liver tumors seen in TGF-alpha transgenic mice
      with regard to histology and strong expression of mouse and human TGF-alpha,
      insulin-like growth factor II, and alpha-fetoprotein mRNAs. Our data show that
      TGF-alpha overexpression causes autonomous hepatocyte proliferation and
      contributes to neoplasia but that additional cellular alterations must occur for
      carcinogenesis. Inappropriate expression of insulin-like growth factor II may
      constitute one of these steps. The TGF-alpha transgenic mouse hepatocyte line
      TAMH appears to undergo transformation in a similar manner to that of hepatocytes
      overexpressing TGF-alpha in vivo, and should serve as an ideal system in which to
      study hepatocarcinogenesis.

PMID- 7525055
TI  - Simultaneous dose escalation and schedule intensification of carboplatin-based
      chemotherapy using peripheral blood progenitor cells and filgrastim: a phase I
      trial.
AB  - Our purpose was to determine the maximum tolerated dose of, and the minimum
      interval between treatments with, multiple cycles of carboplatin (CBDCA) rescued
      with peripheral blood progenitors and filgrastim. Eligible patients had advanced
      cancers without prior chemotherapy or radiotherapy. The study design involved a
      sequential cross-over in which patients initially received two or three courses
      of cyclophosphamide (CPA) at a dose of 3.0 g/m2, supported by filgrastim.
      Multiple leukaphereses were then performed during the rebound phase of
      hematological recovery following each CPA-induced nadir to harvest peripheral
      blood progenitors, which were then reinfused as rescue following each of four
      courses of CBDCA. We attempted to administer the CBDCA at 14-day intervals. The
      CBDCA dose (mg/m2/course) was escalated as follows in successive cohorts of
      patients: Level I, 500; Level II, 800; Level III, 1200; Level IIIa, 1000.
      Following determination of the maximum tolerated dose of CBDCA administered in
      this fashion, a subsequent cohort of patients (Level IV) were treated with two
      courses of high-dose CPA and four courses of the combination of CBDCA (1000
      mg/m2) plus CPA (1500 mg/m2). Thirty-one patients were enrolled in the trial.
      Five patients were removed from study prior to completion of protocol therapy,
      three due to toxicity and two who developed progressive cancer while on study.
      The maximum tolerated dose of CBDCA was 1000 mg/m2, with dose-limiting
      ototoxicity occurring at 1200 mg/m2. The median inter-treatment interval for all
      cycles was 15 days (range, 12-30). The median intervals between CBDCA courses for
      each dose level were: Level I, 17 days; Level II, 17 days; Level III, 14 days;
      Level IIIa, 15 days; Level IV, 16 days. The median dose intensity of the CPA
      phase was 1493 mg/m2/week. The median (and range) CBDCA dose intensities
      (measured from the start of CBDCA) for each dose level were: I, 185 (151-222);
      II, 328 (305-380); III, 567 (512-646); IIIa, 465 (363-481); Level IV, 468 (333
      500). Neutropenic fever complicated 35 of 113 CBDCA or CBDCA/CPA courses.
      Platelet transfusion was required in 51 of 113 courses. One patient had severe
      epistaxis. There were no treatment-related deaths. Among 27 patients with ovarian
      cancer who were evaluable for response, there were 5 pathologically documented
      complete (including 3 of 10 at Level IV) and 16 partial responses. We concluded
      that peripheral blood progenitors facilitate the simultaneous dose escalation and
      schedule intensification of carboplatin chemotherapy. The effect is sustained
      over four courses of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525056
TI  - Lysophosphatidic acid-depleted serum, hepatocyte growth factor and stem cell
      growth factor stimulate colony growth of small cell lung cancer cells through a
      calcium-independent pathway.
AB  - Serum stimulates both Ca2+ mobilization and colony growth of many small cell lung
      cancer (SCLC) cell lines, but the factors involved remain unknown. We demonstrate
      that 1-oleoyl-lysophosphatidic acid (LPA), like serum, induced a dose-dependent
      increase in intracellular Ca2+ in the H-510, H-345, and H-69 SCLC cell lines with
      half maximal concentrations of 18 nM, 22 nM, and 20 nM, respectively. Two lines
      of evidence revealed that LPA was the major factor in serum responsible for
      mobilizing Ca2+ in these SCLC cell lines: (a) both LPA and serum exhibited cross
      desensitization in the Ca2+ mobilization assay; and (b) phospholipase B
      pretreatment of either LPA or serum prevented the ability of these agents to
      stimulate Ca2+ mobilization. In marked contrast, LPA at concentrations between 2
      nM and 20 microM, unlike serum, failed to stimulate colony formation.
      Furthermore, phospholipase B treatment of serum did not inhibit serum-induced
      colony formation. We therefore searched for growth factors which could induce
      colony growth through a Ca(2+)-independent pathway. We found that both human
      recombinant hepatocyte growth factor and stem cell growth factor increased colony
      growth, but failed to stimulate an increase in intracellular Ca2+ in the H-510, H
      345, and H-69 SCLC cell lines. Our results indicate that LPA-depleted serum,
      hepatocyte growth factor, and stem cell growth factor stimulate colony formation
      in SCLC cells through a Ca(2+)-independent pathway.

PMID- 7525054
TI  - Promotional effect of two-generation exposure to a high-fat diet on prostate
      carcinogenesis in ACI/Seg rats.
AB  - Epidemiological studies have shown an association between a high-fat diet and a
      high mortality rate from breast, colon, and prostate cancer. However, the
      promotional effect of a high-fat diet on experimental carcinogenesis has not been
      fully established for the prostate. In this study, the effect on prostatic
      carcinogenesis of two-generation exposure to a high-fat diet was investigated
      using ACI/Seg rats, a strain with high incidence of spontaneous prostate cancer.
      A high-fat diet (20% corn oil) or a low-fat diet (5% corn oil) was given to
      mother rats during pregnancy and the newborn male rats were fed the same diets
      for 60 or 100 weeks after weaning. At 100 weeks, atypical hyperplasia and
      adenocarcinoma of the prostate were respectively found in 73.3% (11/15) and 20.0%
      (3/15) of the high-fat diet group and in 20.0% (3/15) and 0% (0/15) of the low
      fat diet group. There was a significant increase of atypical hyperplasia in the
      high-fat diet group (P < 0.05). The serum concentrations of sex hormones and the
      prostatic proliferative activity as measured by flow cytometry or
      bromodeoxyuridine labeling were not significantly affected by diet. These results
      showed that feeding a high-fat diet before conception and from the beginning of
      organogenesis had a marked promotional effect on the early stage of prostate
      carcinogenesis in rats.

PMID- 7525058
TI  - Current approaches to targeting cancer using antiangiogenesis therapies.

PMID- 7525057
TI  - H blood group antigen carried by CD44V modulates tumorigenicity of rat colon
      carcinoma cells.
AB  - Expression of carbohydrate ABH blood group antigens is oncodevelopmentally
      regulated and their presence on tumor cells constitutes a prognostic factor.
      However, it is not clear whether they directly affect tumor behavior. Using a rat
      model of colon carcinoma, we previously observed an association between the
      presence of H blood group antigens and tumorigenicity in syngeneic animals. In
      the present study, we show by immunoprecipitation experiments that cell surface H
      blood group antigens of a highly tumorigenic clone (PROb) are essentially carried
      by splice variants of the CD44 molecule containing exon V6. PROb cells were then
      transfected with an antisense fragment of the gene coding for a rat alpha (1
      2)fucosyltransferase. This enzyme allows synthesis of H antigens from various
      beta-galactoside precursors. Transfected subclones of PROb cells were obtained
      which had significantly decreased enzymatic activity and H antigenic cell surface
      levels. In contrast, no such changes were observed in control cells transfected
      with either the empty vector or with a sense fragment of the gene. Compared to
      controls, the antisense-transfected cells were far less tumorigenic in syngeneic
      animals. These results show that H blood group antigens at the surface of PROb
      colon carcinoma cells contribute to tumor progression. The presence of the
      fucosylated structures on CD44 could modulate the functions of this adhesion
      molecule.

PMID- 7525059
TI  - Cytotoxicity of white blood cells activated by granulocyte-colony-stimulating
      factor, granulocyte/macrophage-colony-stimulating factor and macrophage-colony
      stimulating factor against tumor cells in the presence of various monoclonal
      antibodies.
AB  - Unconjugated monoclonal antibodies (mAb) kill tumor cells in vivo by activating
      immune functions. One of these is ADCC (antibody-dependent cellular
      cytotoxicity). The efficacy of mAbs might be augmented if the cytotoxic capacity
      of the effector cells could be increased. In this study the augmenting effect of
      granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage(GM)-CSF and
      macrophage(M)-CSF was analyzed. Effector cells [peripheral blood mononuclear
      cells (PBMC) or granulocytes] were activated for 4-6 h by the respective CSF and
      assayed in an 18-h Cr51-release assay. Human colorectal, lymphoma, glioma and
      melanoma cell lines were target cells. Mouse mAbs of different isotypes, as well
      as chimeric and humanized mAbs, were used. mAbs having the human Fc part of the
      IgG molecule were the most effective. The killing capacity of PBMC as well as of
      granulocytes was statistically significantly enhanced when mAbs were added. M-CSF
      and GM-CSF were the best CSF for augmenting the lytic capacity of PBMC in ADCC. G
      CSF had no significant effect on PBMC. Spontaneous cytolysis of PBMC was
      significantly augmented only by M-CSF. Granulocytes were, in general,
      significantly less effective than PBMC but may be equally effective killer cells
      together with mouse or human mAbs of the IgG1 isotype, particularly against
      melanoma cells. Granulocytes may also be significantly stimulated to increased
      lytic capacity when activated with G-CSF or GM-CSF. On the basis of the present
      evaluation, clinical trials in tumor patients are warranted, combining mAbs with
      GM-CSF or M-CSF. Preference might be given to GM-CSF as this cytokine activates
      both PBMC and granulocytes.

PMID- 7525060
TI  - Adenosine receptor specificity in preconditioning of isolated rabbit
      cardiomyocytes: evidence of A3 receptor involvement.
AB  - OBJECTIVE: The aim was to further characterise an experimental model of
      preconditioning of isolated rabbit cardiomyocytes and to determine the role of
      adenosine receptor subtypes in initiation of the protective response. METHODS:
      Isolated myocytes were subjected to 5 min preincubation in the presence or
      absence of glucose and various agonists and antagonists of adenosine receptors.
      Ischaemic pelleting was preceded by a 30 min postincubation period. Rate and
      extent of injury during ischaemia was determined by sequential sampling of the
      pelleted cells and assessment of trypan blue permeability following 85 mOsm
      swelling. RESULTS: Myocytes were preconditioned with a 30-50% reduction of injury
      by a 5 min glucose-free preincubation. Substitution of 5 mM pyruvate for glucose
      during preincubation did not prevent the protective response. Protection was
      maintained over a 60-180 min postincubation period. Protection was blocked by 100
      microM of the non-specific adenosine A1/A2 antagonist SPT, both when added only
      during preincubation or only into the ischaemic pellet. Calphostin C, a specific
      protein kinase C inhibitor at 200 nM, added to the ischaemic pellet blocked
      protection. Preincubation with R-PIA, the adenosine A1 agonist, did not
      precondition at an A1 selective dose of 1 microM, but did at 100 microM. The
      selective A2 agonist CGS 12680 (1 microM) did not precondition. The selective
      A1/A3 adenosine agonist, APNEA, preconditioned at 1 microM and 200 nM dose
      levels. Preconditioning induced either by 200 nM APNEA or by glucose-free
      preincubation was not blocked by 200 nM or 10 microM of the A1 antagonist DPCPX,
      which has extremely low affinity for A3 receptors, but was blocked by 1 microM of
      the A1/A3 adenosine antagonist BW 1433U83. CONCLUSIONS: Preconditioning can be
      induced in isolated myocytes by a 5 min preincubation/30 min postincubation
      protocol, and a similar protection induced by adenosine agonists with A3, but not
      A1 selectivity. Preconditioning is blocked by non-selective or selective A1/A3
      adenosine antagonists and a specific protein kinase C inhibitor, but not by A1
      antagonists with little affinity for A3 receptors. The results suggest that
      preconditioning in isolated rabbit myocytes requires participation of adenosine
      receptors with agonist/antagonist binding characteristics of the A3 subtype, and
      is likely to be mediated by activation of protein kinase C.

PMID- 7525061
TI  - Upregulation of vascular endothelial growth factor expression induced by
      myocardial ischaemia: implications for coronary angiogenesis.
AB  - OBJECTIVE: The process of coronary collateral development is poorly understood.
      It is assumed that particular angiogenic factors are upregulated during episodes
      of myocardial ischaemia and act as a trigger for neovascularisation. However, the
      identity of these factors is unknown. The angiogenic factor vascular endothelial
      growth factor (VEGF) has been shown to be hypoxia inducible, so this factor may
      mediate ischaemia induced angiogenesis in the heart. The aim of this study was to
      examine hypoxia inducibility of VEGF in cultured myocardial cells as well as in
      normally perfused and ischaemic porcine myocardium. METHODS: (1) In vitro
      experiment: cultured rat myocardial cells were subjected to hypoxia, and steady
      state levels of VEGF mRNA were measured after 2 and 4 h of hypoxia. (2) In vivo
      experiment: myocardial ischaemia in pigs hearts was induced by repeated 2-10 min
      left anterior descending coronary artery occlusions, separated by 20 min of
      reperfusion. Hearts were retrieved after 6 h of intermittent ischaemia. Total RNA
      was extracted from normal and ischaemic zones of the heart and processed for RNA
      blot hybridisation analysis. RESULTS: In vitro experiment: as soon as 2-4 h after
      exposure of cultures to hypoxia, VEGF mRNA levels were significantly raised (6-10
      fold). In vivo experiment: VEGF expression was significantly augmented in the
      ischaemic territory of the myocardium (three- to fivefold induction).
      Furthermore, polymerase chain reaction amplification of the reverse transcribed
      mRNA showed increased production of multiple forms of differentially spliced VEGF
      mRNA in the ischaemic myocardium. CONCLUSIONS: VEGF production in the myocardium
      is significantly upregulated by hypoxia in vitro and by ischaemia in vivo. These
      results suggest that VEGF is a likely mediator in the natural process of
      ischaemia induced myocardial neovascularisation.

PMID- 7525063
TI  - Monoclonal antibody to P-selectin (PB1.3) protects against myocardial reperfusion
      injury in the dog.
AB  - OBJECTIVE: The aim was to determine whether a monoclonal antibody directed at P
      selectin (PB1.3) would diminish neutrophil accumulation and protect against
      decrease in coronary flow reserve and myocardial function after coronary
      occlusion-reperfusion. METHODS: Sixteen open chest anaesthetised dogs were
      randomly given PB1.3 (2 mg.kg-1) or buffer intravenously after 50 min of total
      left anterior descending coronary artery occlusion. Ten minutes later, the artery
      was reperfused for 1 h. Coronary flow reserve was measured as peak reactive
      hyperaemic flow and as increase in coronary flow in response to acetylcholine and
      glyceryl trinitrate. Myocardial contractile fraction was measured by ultrasonic
      crystals. Neutrophil infiltration and oxidative burst in the reperfused area were
      also measured. RESULTS: Coronary flow reserve and myocardial contractile function
      were markedly impaired in the supply region following left anterior descending
      coronary artery occlusion-reperfusion in the buffer treated dogs. In contrast,
      both coronary flow reserve and contractile fraction were preserved in PB1.3
      treated dogs despite coronary occlusion-reperfusion. Myeloperoxidase, an index of
      neutrophil infiltration, was increased in the reperfused region in buffer treated
      dogs, but not in the PB1.3 treated dogs. Myocardial histology confirmed the
      reduction in neutrophil accumulation in the reperfused regions in PB1.3 treated
      dogs. Flow cytometry of the regions supplied by the left anterior descending
      coronary artery showed a marked decrease in neutrophil oxidative burst in the
      reperfused region in these dogs. CONCLUSIONS: Antibody to P-selectin (PB1.3)
      protects against attenuation of coronary flow reserve and myocardial contractile
      function after coronary occlusion-reperfusion, and decreases neutrophil
      deposition and activation in the reperfused region.

PMID- 7525065
TI  - [The frequency of viral hepatitis C in patients with porphyria cutanea tarda].
AB  - BACKGROUND: High frequency of hepatitis C virus antibodies was recently
      ascertained in chronic hepatic porphyria in several European countries. Some
      authors correlate these findings with the development of PCT, considering
      hepatitis C-infection further factor capable of triggering clinical and
      laboratory manifestation of this enzymopathy. The task of the present work was to
      ascertain the frequency of HCV antibodies in PCT in Czech Republic by examining
      an extensive group of patients, followed at the porphyria-advise center. METHODS
      AND RESULTS: The frequency of HCV antibodies was investigated in 92 PCT-patients
      with the second-generation enzymatic ELISA method. At the same time, urinary
      porphyrin excretion and liver function tests were examined in these subjects.
      Simultaneously also the results of liver biopsy performed at the first
      presentation of the patients were taken into account. Statistically significant
      increase of anti-HCV antibodies (21.7%) was found in PCT-group in comparison with
      the results of the group of healthy blood donors (0.16%). CONCLUSIONS: HCV
      infection might possibly be a factor responsible for the development of PCT in
      case of proven time-dependent link between the existence of its active viraemic
      phase and initial symptoms of porphyria. Such an evidence has not been provided
      yet and remains a task for future studies.

PMID- 7525064
TI  - Bradykinin-responsive cells of dorsal root ganglia in culture: cell size, firing,
      cytosolic calcium, and substance P.
AB  - 1. We analyze bradykinin-sensitive cells of the mouse dorsal root ganglion in
      culture from the viewpoints of cell size, electrical responses, and Ca2+
      concentration change due to bradykinin and immunocytochemistry of substance P. 2.
      Sixteen percent of cells in the cell group 26-30 microns in diameter fired in
      response to 10 microM bradykinin. None of other cell groups showed a firing
      response to bradykinin. 3. We measured a cytosolic Ca2+ change due to bradykinin
      using a Ca(2+)-sensitive fluorescent dye, Fura 2. The rapid rise (peak time, 20
      sec) in the Ca2+ concentration was ascribed to Ca2+ release from intracellular
      Ca2+ stores. The profound change in the Ca2+ concentration was observed again in
      the cell group 26-30 microns in diameter. Seventeen percent of cells in this
      group increased the Ca2+ concentration by approximately seven times that at
      resting level. 4. Among cells which increase Ca2+ concentration responding to
      bradykinin, 83% of them contain substance P (an immunocytochemical study). 5. We
      conclude that 16-17% of the cell group 26-30 microns in diameter of the dorsal
      root ganglia in culture are polymodal nociceptors and respond to bradykinin.

PMID- 7525062
TI  - Responsiveness of in situ canine nodose ganglion afferent neurones to epicardial
      mechanical or chemical stimuli.
AB  - OBJECTIVE: The aim was to determine the capacity of nodose ganglion afferent
      neurones with epicardial sensory endings to respond to mechanical and chemical
      stimuli, in particular to purinergic compounds. METHODS: Alterations in
      spontaneous activity generated by epicardial afferent neurones in nodose ganglia
      in situ of 17 anaesthetised dogs were identified using extracellular recording
      techniques when mechanical and chemical stimuli were applied to their receptor
      fields, as well as during brief periods of coronary artery occlusion. RESULTS: 92
      cardiac afferent neurones were identified. Localised epicardial distortion
      modified the activity generated by 34 neurones [0.19(SEM 0.02) to 1.2(0.4)
      impulses.s-1]. Application of bradykinin, substance P, N6-cyclopentyladenosine or
      beta, gamma-methylene adenosine 5'-triphosphate to localised epicardial fields
      altered the activity of 69 neurones. Thus the majority of identified epicardial
      neurones responded to chemical stimuli alone (63%) as opposed to mechanical
      stimuli alone (25%), 12% responding to both types of stimuli. Activity was
      enhanced overall by chemical stimuli from a mean range of 0.1-0.4 to 11.6-13.2
      impulses.s-1. Following termination of short lasting chemical as opposed to
      mechanical stimuli, activity remained increased for up to 45 min. Activity
      generated by 16 chemosensitive neurones was modified by brief periods of coronary
      artery occlusion [0.26(0.12)-1.66(0.61) impulses.s-1]; activity increasing
      further [2.51(0.47) impulses.s-1] during reperfusion periods. CONCLUSIONS: (1)
      Chemical stimuli induce an order magnitude greater enhancement of activity
      generated by nodose ganglion cardiac afferent neurones than do mechanical
      stimuli, such enhancement persisting long after removal of chemical as opposed to
      mechanical stimuli. Thus qualitative and quantitative differences exists between
      central neuronal inputs derived from nodose ganglion epicardial afferent neurones
      sensitive to chemical as opposed to mechanical stimuli. (2) Adenosine and ATP can
      activate nodose ganglion cardiac afferent neurones.

PMID- 7525066
TI  - Endocardial endothelium in the rat: junctional organization and permeability.
AB  - Selective permeability of endocardial endothelium has been suggested as a
      mechanism underlying the modulation of the performance of subjacent myocardium.
      In this study, we characterized the organization and permeability of junctional
      complexes in ventricular endocardial endothelium in rat heart. The length of
      intercellular clefts viewed en face per unit endothelial cell surface area was
      lower, and intercellular clefts were deeper in endocardial endothelium than in
      myocardial vascular endothelium, whereas tight junctions had a similar structure
      in both endothelia. On this basis, endocardial endothelium might be less
      permeable than capillary endothelium. However, confocal scanning laser microscopy
      showed that intravenously injected dextran 10,000 coupled to Lucifer Yellow
      penetrated first the endocardial endothelium and later the myocardial capillary
      endothelium. Penetration of dextran 10,000 in myocardium occurred earlier through
      subepicardial capillary endothelium than through subendocardial capillary
      endothelium. Penetration of tracer might thus be influenced by hydrostatic
      pressure. Dextran of MW 40,000 did not diffuse through either endocardial
      endothelium or capillary endothelium. The ultrastructure of endocardial
      endothelium may constitute an adaptation to limit diffusion driven by high
      hydrostatic pressure in the heart. Differences in paracellular diffusion of
      dextran 10,000, between endocardial endothelium and myocardial vessels, may
      result from differing permeability properties of the endocardium and underlying
      myocardium.

PMID- 7525069
TI  - Transient expression of bile-duct-specific cytokeratin in fetal mouse
      hepatocytes.
AB  - The differentiation of hepatocytes and biliary epithelial cells has been
      histochemically analyzed with anti-calf cytokeratin antiserum in the fetal mouse
      liver. Almost all young fetal hepatocytes transiently express bile-duct-specific
      cytokeratin; subsequently, the strong staining of the cytokeratin is confined to
      progenitor cells of intrahepatic biliary epithelial cells around portal veins.
      These results suggest that all fetal hepatocytes are bi-potent in terms of the
      differentiation of mature hepatocytes and intrahepatic bile-duct cells, and that
      the microenvironment around portal veins plays an important role in bile-duct
      differentiation. Large periportal hepatocytes continue to stain weakly for
      cytokeratin until 2 weeks after birth, although the number of positive
      hepatocytes decreases with development. The differentiation of bile ducts from
      periportal hepatocytes may continue for 2 weeks after birth.

PMID- 7525068
TI  - The immunosuppressant FK506 inhibits the damage to mouse pancreatic islets
      induced by low dose streptozocin.
AB  - Diabetes mellitus was induced in 40 male C57BL6 mice by injection of a low dose
      of streptozocin (45 mg/kg body weight) on 5 consecutive days. Twenty four of the
      mice were immunosuppressed by administration of 1.5 mg FK506/kg body weight daily
      for 10, 15, 18 and 24 days. Administration of FK506 almost completely inhibited
      the streptozocin-induced islet damage, and consequently glycaemia remained
      normal. In FK506-treated animals any inflammatory infiltrate was very sparse and
      was limited to the vascular pole of the islets. Immunocytochemical results
      demonstrated that infiltrating cells were Ia-immunoreactive, but were not
      activated. Ultrastructural observations confirmed the absence of B cell necrosis
      and degranulation in FK506-treated mice; the few infiltrating elements
      encountered did not contain phagocytic vesicles or show other signs of
      activation.

PMID- 7525067
TI  - Nitrergic innervation and nitrergic cells in arteriovenous anastomoses.
AB  - Nitrergic innervation and nitrergic epithelioid cells were studied in
      arteriovenous anastomoses of the tongue, ear, eye, and glomus organ of the finger
      in different species (rat, rabbit, dog, and man), by means of
      immunohistochemistry for nitric oxide synthase and enzyme histochemistry
      utilizing the catalytic activity of this enzyme (the NADPH-diaphorase reaction).
      Nitrergic perivascular fibers of the tongue were concentrated along the arterial
      tree and were maximal at the arteriovenous anastomoses in all species. Generally,
      fewer fibers were located around comparable segments of the episcleral eye
      vasculature. Only a few nitrergic fibers were found in the canine and rabbit ear,
      and in the glomus organ of the human finger; however, epithelioid cells in the
      tunica media of arteriovenous anastomoses of these organs were NADPH-diaphorase
      positive and were moderately immunoreactive for nitric oxide synthase. In the
      epithelioid cells, the reaction product of the NADPH-diaphorase could also be
      demonstrated by transmission electron microscopy. The epithelioid cells were
      negative for the panneural and neuroendocrine marker PGP 9.5 confirming the
      myocytotic nature of these nitrergic cells. Thus, nitric oxide might play a role
      in mediating the vessel tone of arteriovenous anastomoses via nitrergic nerves or
      epithelioid cells.

PMID- 7525070
TI  - Comparative study of immature erythroid cells of the diploid Bufo ictericus and
      the tetraploid Odontophrynus americanus (Amphibia, Anura): ultrastructural
      cytochemical detection of nucleic acids and polysaccharides, and mapping of the
      element phosphorus.
AB  - In the present study, we used ultrastructural cytochemistry to analyze the
      distribution of nuclear and cytoplasmic nucleic acids and polysaccharides, and
      electron spectroscopic imaging to map the element phosphorus in immature
      erythroid cells taken from two amphibians, the diploid Bufo ictericus and the
      tetraploid Odontophrynus americanus. In the cytoplasm of cells from the
      tetraploid species, we detected numerous inclusions containing a material that
      was similar to the dispersed chromatin seen in the nucleus of these cells. The
      RNase-gold complex labeled both the dispersed nuclear chromatin and the
      cytoplasmic inclusions. The Thiery technique showed that glycoconjugates were
      present in all the membranous complexes of the erythroid cells of both types of
      amphibians under study, although they were absent within or around the
      cytoplasmic RNA inclusions. Electron spectroscopic imaging revealed the presence
      of phosphorus in these inclusions. These data suggest that an increase in RNA
      synthesis occurs in tetraploid amphibian cells, probably as a result of an
      alteration in the mechanisms of gene regulation.

PMID- 7525071
TI  - Problems encountered when immunocytochemistry is used for quantitative glial cell
      identification in autoradiographic studies of cell proliferation in the brain of
      the unlesioned adult mouse.
AB  - We have used sections of adult mouse brain to determine whether antibodies
      specific for oligodendroglia (anti-carbonic anhydrase II, CA II; anti
      galactocerebroside, GC; anti-myelin basic protein, MBP) and astroglia (anti-glial
      fibrillary acidic protein, GFAP; anti-S 100 protein) are suitable for
      quantitative studies of the proliferation and subsequent differentiation of these
      cells. Unlesioned adult mice received a single injection of 3H-thymidine (TdR)
      and were killed between 1 h and 70 days later. Quantitative evaluations of
      autoradiographs of 2-microns-thick serial sections stained immunocytochemically
      with the antibodies mentioned above or with Richardson's method for histological
      control led to the following conclusions. Anti-GC and anti-MBP stained only the
      oligodendrocytic processes and, thus, cannot be used in well-myelinated brain
      areas. Anti-CA II stained only a portion of the differentiated oligodendrocytes,
      but no proliferating cells. Anti-S 100 protein recognized all the astrocytes, but
      also many (interfascicular) oligodendrocytes. Anti-GFAP stained only a few
      astrocytes in the unlesioned mouse; all astrocytes may become GFAP-immunopositive
      only after wounding the brain. Thus, in contrast to in vitro studies,
      immunocytochemical studies with these antibodies on sections of adult animals
      cannot be recommended for the quantitative analysis of cell proliferation. In
      addition, our results show that differentiated glial cells proliferate in adult
      mice. Astro- and oligodendrocytes divide with the same cell cycle parameters and
      mode of proliferation up to about 1 month after 3H-TdR injection. In contrast to
      oligodendrocytes, some astrocytes might re-enter the cycle after a few weeks of
      quiescence.

PMID- 7525072
TI  - Independent external calcium entry and cellular calcium mobilization in Xenopus
      oocytes.
AB  - We studied cellular calcium (Ca) mobilization and Ca entry from the medium
      following injection of various inositol phosphates (IPs) or activation of
      thyrotropin-releasing hormone receptors (TRH-Rs) in oocytes injected with TRH-R
      cRNA. We determined the order of potency of various IPs for evoking the rapid
      depolarizing current in Ca-free medium, which reflects the mobilization of
      cellular Ca. The most potent compound was inositol 1,4,5-trisphosphate
      (Ins(1,4,5)P3), followed by inositol 1,2,4,5-tetrakisphosphate (Ins(1,2,4,5)-P4),
      which displayed 91% of the activity of Ins(1,4,5)P3, while inositol 1,3,4,6
      tetrakisphosphate (Ins(1,3,4,6)P4) had only 29% effect. All other IPs used in the
      present study exhibited responses that were 40% or less than those elicited by
      Ins(1,4,5)P3. Cellular Ca mobilization was confirmed by 45Ca2+ efflux for
      Ins(1,4,5)P3, Ins(1,2,4,5)P4 and Ins(1,3,4,6)P4, or by Fura-2 ratio imaging
      studies for the latter. In parallel, we assayed the ability of these compounds to
      promote Ca entry into the cell, as reflected by Ca-evoked depolarizing current or
      Fura-2 imaging. These assays revealed a different order of potency, where
      Ins(1,4,5)P3 > inositol 4,5-bisphosphate (Ins(4,5)P2) > Ins(1,3,4,6)P4 =
      Ins(1,2,4,5)P4. All other inositol phosphates were largely ineffective. Heparin
      inhibited the response to TRH by 67% while Ca entry was inhibited only by 22%.
      The latency of the response to TRH was significantly shorter in the presence of
      extracellular Ca, suggesting Ca entry preceded the response, i.e. major depletion
      of Ca stores. These results strongly suggest that the activation of Ca entry is
      largely independent of cellular Ca mobilization and may be mediated by a receptor
      for an unidentified phosphorylated compound, different from that for Ins(1,4,5)P3
      on the endoplasmic reticulum.

PMID- 7525073
TI  - Calcium and melatonin production in dissociated trout pineal photoreceptor cells
      in culture.
AB  - Trout pineal cells maintained in primary culture produce melatonin in high
      amounts during night time and low amounts during daytime. The dark-induced
      increase in melatonin production was enhanced, in a dose-dependent manner, by
      elevating extracellular calcium concentration. Low external calcium concentration
      reduced nocturnal and diurnal melatonin production. Bay K 8644 increased, in a
      dose-dependent manner, the dark-induced rise in melatonin output, and this effect
      was antagonized by nifedipine and verapamil. This suggests a role for the
      dihydropyridine calcium channels in the regulation of the melatonin output. To
      confirm this, patch-clamp recordings (whole-cell perforated) were run in a 20
      mmol/l barium medium at different holding potentials from -80 mV. A voltage
      dependent inward current was activated from -30 mV to +40 mV with a maximal
      amplitude being observed at 0 mV. This current was drastically increased in the
      presence of Bay K 8644. Nifedipine inhibited the current both in the absence or
      in the presence of Bay K 8644. Our results are consistent with the idea that
      extracellular calcium participates in the control of melatonin secretion by
      photoreceptor cells. It is suggested that activation of the voltage-dependent L
      type channel may modulate this secretion.

PMID- 7525074
TI  - Dogs, dextran, and dilatation: a story of empiricism run wild.

PMID- 7525075
TI  - Adult respiratory distress syndrome complicating intravenous infusion of low
      molecular weight dextran.
AB  - Respiratory failure is one of the most uncommon and serious adverse drug
      reactions. Low-molecular-weight-dextran (Dextran-40) is a useful adjunctive anti
      platelet agent in the setting of coronary angioplasty and intracoronary stent
      placement. We report the occurrence of the adult respiratory distress syndrome
      following intravenous infusion of Dextran-40.

PMID- 7525076
TI  - The implications of angiogenesis for the biology and therapy of cancer
      metastasis.

PMID- 7525078
TI  - The latch region of calcineurin B is involved in both immunosuppressant
      immunophilin complex docking and phosphatase activation.
AB  - The immunosuppressants cyclosporin A and FK506, when complexed with their
      intracellular receptors, prevent T cell activation by directly binding to the
      phosphatase calcineurin. We have used molecular modeling and mutagenesis to
      identify sites on calcineurin important for this interaction. We have created
      calcineurins that are resistant to both cyclosporin A and FK506 by mutating
      specific residues in CnB, a calcium-binding protein that regulates the catalytic
      subunit, CnA. Significantly, on a model of CnB, these mutations map to the latch
      region, an element of tertiary structure that forms when CnB binds CnA. In
      addition, we show that this latch region plays an important role in activating
      the catalytic subunit CnA. These results suggest a molecular mechanism for
      suppression of calcineurin by cyclosporin A and FK506 involving their binding to
      the same region of CnB used for allosterically activating CnA.

PMID- 7525077
TI  - Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of
      metastases by a Lewis lung carcinoma.
AB  - The phenomenon of inhibition of tumor growth by tumor mass has been repeatedly
      studied, but without elucidation of a satisfactory mechanism. In our animal
      model, a primary tumor inhibits its remote metastases. After tumor removal,
      metastases neovascularize and grow. When the primary tumor is present, metastatic
      growth is suppressed by a circulating angiogenesis inhibitor. Serum and urine
      from tumor-bearing mice, but not from controls, specifically inhibit endothelial
      cell proliferation. The activity copurifies with a 38 kDa plasminogen fragment
      that we have sequenced and named angiostatin. A corresponding fragment of human
      plasminogen has similar activity. Systemic administration of angiostatin, but not
      intact plasminogen, potently blocks neovascularization and growth of metastases.
      We here show that the inhibition of metastases by a primary mouse tumor is
      mediated, at least in part, by angiostatin.

PMID- 7525079
TI  - Identification of a Tap-dependent leader peptide recognized by alloreactive T
      cells specific for a class Ib antigen.
AB  - Recognition of the class Ib antigen Qa-1 by a portion of alloreactive cytotoxic T
      lymphocyte (CTL) clones requires that the target cell express a second gene,
      termed Qa-1 determinant modifier (Qdm). We show that Qdm is identical to most D
      allele genes, excepting Dk, and that a nonamer peptide derived from D
      alloantigens restores CTL recognition on cells that lack the Qdm-encoded
      determinant. The equivalent Dk peptide has an Ala-->Val interchange at P3 and
      requires approximately 4 logs more peptide than the AlaP3 peptide for target cell
      lysis. Two of five CTL clones, not dependent on Qdm for target cell recognition,
      also recognize the Qdm peptide as well as the ValP3 variant. Although the Qdm
      peptide spans residues 3-11 from the leader, it requires the Tap transporters for
      its expression. Thus, the response against this class Ib molecule provides a tool
      for dissecting alloreactivity as well as pathways for antigen presentation.

PMID- 7525081
TI  - Signals through membrane Ig of peritoneal CD5 B cells to suppress LPS-induced Ig
      secretion.
AB  - Murine peritoneal CD5 B cells include many B cells reactive with bromelain
      treated mouse RBC (BrMRBC). Anti-BrMRBC B cells are through to expand after
      selection by self-antigens, but little is known about signals through their
      membrane Ig (mIg). Most anti-BrMRBC antibodies use VH11 and V kappa 9 genes, and
      VH11/V kappa 9-type antibodies are detectable specifically with rabbit anti
      idiotype antibodies (here referred to as RAIa). Preincubation of peritoneal cells
      with RAIa at 37 degrees C before LPS stimulation reduced LPS-induced secretion of
      RAIa-detectable Ig. To render RAIa-reactive B cells hyporesponsive, a continuous
      reaction of their mIg with RAIa was necessary. Binding of BrMRBC to RAIa-reactive
      B cells hardly affected their LPS reactivity. It appears that fresh mIg deliver
      the suppressive signals after reacted with RAIa, and the degree of
      hyporesponsiveness of a RAIa-reactive B cell depends on the amount of mIg-RAIa
      complexes. RAIa-suppressed B cells could regenerate mIg in the absence of RAIa
      and could respond to LPS to enlarge. It is suggested that binding of RAIa to mIg
      renders RAIa-reactive B cells without proliferation in an anergy state, where
      synthesis of secretory Ig is rather specifically suppressed.

PMID- 7525080
TI  - Ligand and cation binding are dual functions of a discrete segment of the
      integrin beta 3 subunit: cation displacement is involved in ligand binding.
AB  - The alpha IIb beta 3 integrin binds Arg-Gly-Asp-containing (RGD-containing)
      ligands in a cation-dependent interaction. A fourteen amino acid sequence, beta 3
      (118-131), and an antibody to it, inhibited ligand binding functions of alpha IIb
      beta 3, and a 1:1 stoichiometric beta 3 (118-131)-RGD complex was detected by
      mass spectroscopy. Cation binding to beta 3 (118-131) was demonstrated by terbium
      luminescence and mass spectroscopy. Notably, ligand displaced cation from the
      beta 3(118-131) peptide and also from purified alpha IIb beta 3. Thus, beta 3
      (118-131), a highly conserved region in integrin beta subunits, binds both ligand
      and cation. Formation of a ternary complex between cation, ligand, and receptor,
      with subsequent displacement of cation from beta 3 (118-131) and a second site
      within the receptor, may be central to the mechanism of ligand recognition by
      integrins.

PMID- 7525082
TI  - Modulation of the expression of CD5 antigen on the surface of human peripheral B
      lymphocytes.
AB  - In this study, we investigated the expression of CD5 molecules on the surface of
      mature human peripheral B lymphocytes. Human CD5+ B cells were isolated from
      tonsils and peripheral blood. Their terminal differentiation into plasma cells
      was induced with IL-2. In the presence of this lymphokine, a subset of CD5+ B
      cells ceased to express CD5 proteins on their surface. When CD5+ B cells and non
      B cells were removed from the suspension. CD5 antigens were spontaneously
      reexpressed on the surface of CD5- B cells. This suggests that the CD5- phenotype
      of a subset of B cells in these suspensions resulted from pressure(s) exerted on
      them by the other cellular components of the suspensions. B cells which have
      reexpressed membrane CD5 in the absence of CD5+ B cells and non-B cells retained
      their ability to reprogress to CD5- phenotype and to undergo terminal
      differentiation into plasma cells when stimulated with IL-2. A short exposure (4
      hr) of CD5- B cells to 5 nM IL-2 resulted in the loss of their capability to
      spontaneously reexpress surface CD5 in the absence of other lymphoid cells. Taken
      together, these data suggest that the expression of CD5 antigens on B cell
      membrane is governed by a network-type balance between all cellular compartments
      within the suspension. Fluctuations of this equilibrium results in the shuttling
      of B cells between CD5+ and CD5+ phenotypes until they become irreversibly
      engaged in the terminal differentiation pathway. The interconversion CD5+<==>CD5-
      on B cell membrane does not argue for CD5 molecule as the marker of a distinct B
      cell lineage.

PMID- 7525083
TI  - The acute phase response: general aspects.
AB  - The acute phase response in a given individual represents the integrated sum of
      multiple, separately regulated changes. Although many of these changes commonly
      occur together in affected individuals, clinical experience indicates that not
      all of them occur in all individuals, indicating that they must be individually
      regulated. For example, febrile patients may have normal blood levels of CRP and
      vice versa, leukocytosis does not always accompany other acute phase phenomena,
      and many instances of discordance between levels of the various acute phase
      proteins are seen. Cytokines function as part of a complex regulatory network, a
      signalling language in which information is conveyed to cells by combinations,
      and perhaps sequence, of intercellular messenger molecules. The effects of
      combinations of cytokines are complex. To use a somewhat crude simile, individual
      cytokines can be thought of as words which bear informational content and which
      may, on occasion, communicate a complete message. More commonly, however, the
      actual messages received by cells probably resemble sentences, in which
      combinations and sequences of words convey information. Currently available data
      suggest that hepatocytes receive a complex mixture of humoral or paracrine
      signals during the acute phase response. These are integrated by multiple
      interacting signal transducing mechanisms to cause finely regulated changes in
      plasma protein synthesis. Regulation largely occurs by transcriptional control,
      but post-transcriptional mechanisms, including translational regulation, may also
      participate. Both the extracellular and intracellular mechanisms that mediate the
      response of the hepatocyte to inflammatory stimuli appear to be highly complex
      and involve multiple overlapping, concurrent and parallel pathways. Enough is
      known at present to conclude that IL-6 is a major participant in these plasma
      protein changes. Regulation of non-hepatocyte acute phase phenomena has not been
      delineated as thoroughly, but clearly involves a number of inflammation
      associated cytokines.

PMID- 7525084
TI  - Acute phase proteins in the monitoring of inflammatory disorders.
AB  - The acute phase reaction is in most circumstances a good indicator of (local)
      inflammatory activity and tissue damage. CRP is a direct and quantitative measure
      for the acute phase reaction and due to its fast kinetics provides adequate
      information of the actual situation. The ESR on the contrary is in fact an
      indirect measure of the acute phase reaction. It does react much slower to
      changes of inflammatory activity and is influenced by a number of other factors.
      From studies on the 'behaviour' of CRP it has become clear that diseases may
      differ with regard to the extent in which they induce an acute phase response.
      Incidental measurement of the CRP level may add to the diagnostic procedure in
      selected cases, e.g. in the differentiation between a bacterial and a viral
      infection or between a bacterial infection and an exacerbation of diseases like
      SLE. In case of an extremely elevated CRP level (> 100 mg/litre) the possibility
      of a bacterial infection should always be considered. In clinical practice CRP is
      particularly useful when serial measurements are performed. The course of the CRP
      level may be useful for the monitoring of the effect of treatment and for the
      early detection of postoperative complications or intercurrent infections. The
      relationship between CRP and the local production and effects of cytokines on the
      one hand, and the possible functional role of CRP in the inflammatory process on
      the other hand have surely added a dimension to the clinical use of CRP as a
      parameter of inflammatory activity.

PMID- 7525085
TI  - Serum amyloid A: an acute phase apolipoprotein and precursor of AA amyloid.
AB  - Serum amyloid A is an acute phase protein complexed to HDL as an apoprotein. The
      molecular weight is 11.4-12.5 kDa in different species and the protein has from
      104 to 112 amino acids, without or with an insertion of eight amino acids at
      position 72. The protein is very well conserved throughout evolution, indicating
      an important biological function. The N-terminal part of the molecule is
      hydrophobic and probably responsible for the lipid binding properties. The most
      conserved part is from position 38 to 52 and this part is therefore believed to
      be responsible for the until now unknown biological function. The protein is
      coded on chromosome 11p in man, and chromosome 7 in mice, and found in all
      mammals until now investigated, and also in the Peking duck. In the rat a
      truncated SAA mRNA has been demonstrated, but no equivalent serum protein has
      been reported. Acute phase SAA is first of all produced in hepatocytes after
      induction by cytokines, but extrahepatic expression of both acute phase and
      constitutive SAA proteins have been demonstrated. Several cytokines, first of all
      IL-1, IL-6 and TNF are involved in the induction of SAA synthesis, but the mutual
      importance of these cytokines seems to be cell-type specific and to vary in
      various experimental settings. The role of corticosteroids in SAA induction is
      somewhat confusing. In most in vitro studies corticosteroids show an enhancing or
      synergistic effect with cytokines on SAA production in cultured cell. However, in
      clinical studies and in vivo studies in animals an inhibitory effect of
      corticosteroids is evident, probably due to the all over anti-inflammatory effect
      of the drug. Until now no drug has been found that selectively inhibits SAA
      production by hepatocytes. Effective anti-inflammatory or antibacterial treatment
      is the only tool for reducing SAA concentration in serum and reducing the risk of
      developing secondary amyloidosis. The function of SAA is still unclear.
      Interesting theories, based on current knowledge of the lipid binding properties
      of the protein and the relation to macrophages, in the transportation of
      cholesterol from damaged tissues has been advanced. A putative role in
      cholesterol metabolism is supported by the findings of SAA as an inhibitor of
      LCAT. The potential that SAA is a modifying protein in inflammation influencing
      the function of neutrophils and platelets is interesting and more directly
      related to the inflammatory process itself.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525086
TI  - Cellular polarity correlates with vimentin distribution, but not to keratin, in
      human renal cell carcinoma cells in vitro.
AB  - To investigate the relationships among vimentin, keratin and cellular polarity,
      reorganized glands composed of renal cell carcinoma cells were investigated in
      vitro. We employed two different three-dimensional collagen gel culture methods,
      the "floating sandwich method (FSM)" and the "dispersed embedding method (DEM)."
      The cells composed of reorganized glands formed by FSM culture showed distinct
      polarity. In contrast, the cellular polarity of the cells formed by DEM culture
      was less distinct. Keratin was evenly distributed throughout the cytoplasm
      regardless of the culture method. In contrast, in reorganized glands obtained by
      FSM culture, vimentin was distinctly polarized at the basal pole while glands
      obtained by DEM culture showed random distribution of vimentin. These results
      suggest that there is a close relationship between cell polarity and
      intracellular localization of vimentin, and that there may be different
      mechanisms controlling the organization of the two intermediate filament (IF)
      networks.

PMID- 7525087
TI  - Absolute stereostructures of hydramacrosides A and B, new bioactive secoiridoid
      glucoside complexes from the leaves of Hydrangea macrophylla Seringe var.
      thunbergii Makino.
AB  - Two new bioactive secoiridoid glucoside complexes named hydramacrosides A and B
      were isolated from the leaves of Hydrangea macrophylla SERINGE var. thunbergii
      MAKINO. The absolute stereostructures of hydramacrosides A and B were elucidated
      on the basis of chemical and physicochemical evidence which included the
      application of the 13C NMR glycosylation shift rule of 1, 1'-disaccharides and
      the modified Mosher's method. Hydramacrosides A and B exhibited inhibitory effect
      on the histamine release from rat mast cells induced by antigen-antibody
      reaction.

PMID- 7525088
TI  - Nature of protein adsorption in artificial tear solution on plasma-irradiated
      polymethylmethacrylate surface.
AB  - To evaluate the effect of plasma treatment on protein adsorption onto a polymer
      surface, we carried out Ar plasma irradiation on polymethylmethacrylate (PMMA)
      plate and examined the adsorption behavior of protein after immersion of plasma
      treated PMMA plate in the artificial tear solution containing lysozyme, albumin
      and gamma-globulin. It was found that the total adsorption of protein in the
      artificial tear solution to PMMA is suppressed by the Ar plasma treatment. But
      the adsorption of each component protein differs according to the surface
      condition of polymers and obviously corresponds to the change with time in the
      surface wettability. It is concluded that introduction of a hydrophilic group
      into the PMMA surface by plasma treatment and coming off of it are associated
      with the adsorption behavior of proteins. Since the adsorption of protein to the
      plasma-treated PMMA surface changes over time, care should be exercised in
      determining it, when an attempt is made to clarify the effect of plasma
      irradiation on the adsorption to the plasma-irradiated polymer surface.

PMID- 7525090
TI  - [Cloning and characterization of a specific cytokeratin-8 cDNA from rat prostatic
      epithelium].
AB  - In this study, we report the cloning and sequencing of a full-length cytokeratin
      8 (CK-8) cDNA from a rat prostatic epithelial cDNA library. The effects of
      androgen on CK-8 expression in rat prostate were also studied. The data indicated
      that the steady-state level of CK-8 mRNA was elevated by about 5- to 10-fold in
      both prostate and seminal vesicles in castrated rats, and the elevated levels
      persisted during a 23-day experimental period. Androgen but not estrogen
      administration repressed the expression of CK-8 mRNA. This effect could be
      antagonized by the simultaneous administration of an antiandrogen, flutamide,
      indicating that CK-8 is a new class of androgen-repressed genes whose regulation
      is presumably mediated by androgen receptor mechanisms.

PMID- 7525089
TI  - [A comparative study of the expression of ras oncogenic protein P21 and oncofetal
      protein AFP, CEA in human hepatocellular carcinoma (HCC)].
AB  - The expression of P21, AFP and CEA were detected in human hepatocellular
      carcinoma and its surrounding nontumor tissues by immunohistochemical staining on
      serial sections. The significance of AFP and P21 in HCC auxiliary diagnosis was
      discussed. The results are as follows: (1) AFP and P21 were more closely related
      with HCC than CEA. Both AFP and P21 were expressed simultaneously in more than
      half the cases. The distribution of these two antigens in HCC was similar. (2)
      The positive incidence of AFP in tumor tissues was higher than that in
      surrounding nontumor tissues, but vice versa for P21. Based on the results of
      this study, we regard that AFP is a relatively specific marker of HCC, better
      than P21 in auxiliary diagnosis of HCC. The hepatocytes which surround the tumor
      and can simultaneously express AFP and P21, are likely to be precancerous cells
      which have been initiated and possess the ability of neoplastic growth but lack
      phenotype transformation.

PMID- 7525091
TI  - [The biological properties of two CD71 McAbs].
AB  - Two monoclonal antibodies (McAbs), HI160 and HI166, recognize different epitopes
      of the CD71 antigen. Their biological properties have been studied, and the
      results demonstrated that both had down-regulation effects. HI160 McAb not only
      inhibited the activation and proliferation of T and B lymphocytes but also the
      growth of CFU-GM. HI166 McAb only inhibited the activation and proliferation of T
      lymphocytes. The differences in the biological properties of the two CD71 McAbs
      might be due to the different epitopes recognized by them. The application value
      of these McAbs is discussed.

PMID- 7525092
TI  - Interleukin-6 and tumour necrosis factor during cardiopulmonary bypass.

PMID- 7525093
TI  - Essential drugs for cancer chemotherapy. WHO consultation.
AB  - The WHO recommendation on essential drugs for cancer chemotherapy has been
      updated. General principles on the proper role of cancer chemotherapeutic agents
      in relation to efficacy and on the classification of tumours with respect to
      their curative potential are discussed. Curable cancers and those cancers where
      the cost-benefit ratio clearly favours drug treatment can be managed
      appropriately based on only 24 drugs. Fourteen of them should ideally be
      available for the treatment of the ten most common cancers, 8 others should be
      available only where the resources and facilities exist for the treatment of
      paediatric tumours and leukaemias, and two drugs were recommended for the
      treatment of tumours for which there is good evidence that systemic treatment
      will palliate symptoms but not substantially prolong survival. The adoption of
      these recommendations should result in considerable reduction in both the
      mortality and morbidity from cancer throughout the world.

PMID- 7525094
TI  - Aberrant expression of nitric oxide synthase in human polyps, neoplastic colonic
      mucosa and surrounding peritumoral normal mucosa.
AB  - The expression of nitric oxide synthase (NOS) was studied by NAD(P)H diaphorase
      histochemical localization method in (i) individual cells of the normal colonic
      mucosa (n = 13) which served as control, (ii) colonic polyps (n = 14), (iii)
      colonic carcinoma (n = 20) and (iv) peritumoral mucosa (2 and 5 or 10 cm away
      from the tumor). Four of the tumor specimens had normal epithelium adjacent to
      the cancer, which thus served as an internal control. The expression of NOS
      activity in colon cancer was significantly reduced as compared to the control
      group of individuals (P < 0.004); undetectable in 25%, diminished in 45%, normal
      in 30%. On comparing the expression in normal mucosa and polyps there was a
      significant reduction of the expression in polyps (P < 0.027); undetectable in
      14%, reduced in 35%, normal in 51%. When compared to the peritumoral mucosa at 2
      and 10 cm the tumor showed a significant reduction in expression of NOS activity
      (P < 0.001 and P < 0.0001 respectively). There was no significant difference seen
      in the expression at 2 and 10 cm (P = 0.329). The peritumoral mucosa at a
      distance of 2 cm away from the tumor when compared to the control mucosa showed
      no significant difference (P = 1.000), although there is a tendency to a high
      normal expression of NOS activity in the mucosa at a distance of 2 cm. Similarly,
      there was no significant difference between the control mucosa and the
      peritumoral mucosa obtained at a distance of 10 cm (P = 0.383). The expression of
      NOS activity in all tissues examined was abolished by preincubation of tissue
      with the selective NOS inhibitor L-NMMA but not with D-NMMA. Our data showed
      extensive and significant reduction as identified by the NAD(P)H diaphorase
      method in the expression of NOS activity, thereby reflecting the activity of
      nitric oxide in colon cancer and colonic polyps. The generalized suppression of
      this activity, which precedes the onset of overt neoplasia, may be an important
      event in colon carcinogenesis. This aberrant expression could also be compatible
      with the selective advantage to either tumor promotion and metastatic progression
      or to tumoricidal activity.

PMID- 7525095
TI  - The effect of pyridine on the in vitro and in vivo metabolism of ethyl carbamate
      (urethane) by rat and mouse.
AB  - Ethyl carbamate (EC, urethane) is a known carcinogen in laboratory animals. A
      genotoxic mechanism has been proposed which involves the bioactivation of EC to a
      reactive epoxide by the ethanol-inducible CYP2E1. The purpose of this study was
      to determine if pyridine (200 mg/kg i.p.), an inducer of CYP2E1, would increase
      the in vitro metabolism of EC and the in vivo binding of EC to cellular
      macromolecules. Treatment of rats or mice with pyridine increased hepatic
      microsomal metabolism of [14C-carbonyl]EC to CO2, but had little effect on
      pulmonary microsomal metabolism. The increase in hepatic metabolism was inhibited
      by the CYP2E1 inhibitor diethyldithiocarbamate, but not by the esterase inhibitor
      paraoxon, clearly indicating a role for this isozyme in hepatic metabolism of EC.
      In vivo, pyridine (200 mg/kg i.p.) administered 18 h prior to dosing with EC
      decreased the binding of [14C-ethyl]EC to cellular macromolecules. These data
      indicate that pyridine administration to rats and mice induces CYP2E1 metabolism
      of EC in vitro, but inhibits EC metabolism in vivo, perhaps by acting as an
      alternate substrate for CYP2E1.

PMID- 7525096
TI  - Comparative genotoxicity of 2,3'-O-cyclocytidine, beta-xylocytidine and 1-beta-D
      arabinofuranosylcytosine in human tumor cell lines.
AB  - We have investigated the genotoxicity of two 3'-derivatives of cytidine, 2,3'-O
      cyclocytidine (3'-cycloC) and beta-xylocytidine (xyloC), in human leukemia and
      solid tumor cell lines. Both derivatives were found to be cytotoxic at micromolar
      concentrations. For example, in the alveolar tumor cell line A549 which was
      included in all experiments as a reference, drug concentrations required to
      induce 50% inhibition of cell growth (D50 values) equalled 55 microM for 3'
      cycloC and 80 microM for xyloC. Compared with the response of this reference cell
      line, none of the solid tumor cell lines tested--representing five different
      malignancies--displayed significant hypersensitivity to these drugs, while the
      acute lymphoblastic leukemia cell lines proved to be hypersensitive (range of D50
      values, 5-13 microM). To gain insight into the modes of cytotoxic action of xyloC
      and 3'-cycloC, we compared the effect on DNA metabolism of these compounds with
      that of 1-beta-D-arabinofuranosylcytosine (araC), a potent inhibitor of semi
      conservative DNA replication and long-patch excision repair. As seen with araC,
      the xylo compound strongly inhibited both DNA replicative synthesis and the
      repair of DNA damage induced by UV light and 60Co gamma-radiation. In gamma
      irradiated A549 cells, the extent of repair inhibition by 1 mM xyloC was
      approximately 40% of that inhibited by araC, and concomitant exposure of the
      irradiated cultures to xyloC plus araC gave rise to a synergistic response. Since
      araC was employed at a concentration (0.1 mM) which produced a maximal effect on
      DNA repair when applied alone, the observed synergistic response implies that the
      mode of action of xyloC on DNA repair is different from that of araC. In contrast
      to that observed with xyloC, 3'-cycloC proved to be a very weak inhibitor of DNA
      replication and repair, strongly suggesting that the genotoxic action of the
      latter analog may be through a mechanism other than inhibition of DNA synthesis.

PMID- 7525097
TI  - Immunochemical detection of sequence-specific modifications to DNA induced by UV
      light.
AB  - Sequence specificity of antibodies to UV-damaged DNA has not been described
      previously. The antisera investigated here were specific for UV-modified DNA and
      were absolutely dependent upon the presence of thymine residues. Using a series
      of oligonucleotides in competition ELISA, increased inhibition was observed with
      increasing chain length of UV-polythymidylate. A minimum of three adjacent
      thymines was required for effective inhibition; alone, dimers of thymine were
      poor antigens. Although UV-irradiated poly(dC) was not antigenic, cytosines could
      partially replace thymines within the smallest effective epitope (T-T-T) with a
      high degree of sequence specificity, not previously described. The main epitope
      induced by UV was formed from adjacent thymines and either a 3' or a 5'
      pyrimidine.

PMID- 7525098
TI  - Retinoic acid-induced normal and tumor-associated aberrant expression of the
      murine keratin K13 gene does not involve a promotor sequence with striking
      homology to a natural retinoic acid responsive element.
AB  - The type I keratin K13, normally restricted to suprabasal cells of internal
      stratified epithelia, is aberrantly expressed in 7,12-dimethylbenz[a]anthracene
      (DMBA)-12-O-tetradecanoyl-phorbol-13-acetate-induced murine epidermal tumors and
      constitutes an early marker of malignant progression. Aberrant K13 expression
      also occurs in epidermal cell lines derived from DMBA-TPA-induced tumors. As in
      cultured primary keratinocytes from normal internal stratified epithelia, the in
      vitro expression of K13 in transformed epidermal cell lines can be induced either
      by Ca2+ or by retinoic acid (RA). We have found that the promoter of the K13 gene
      contains a sequence element GGTTCA(N)5TGTTCT, in the following referred to as K13
      RARE, that is highly related to the natural retinoic acid responsive element
      (RARE) of the retinoic acid receptor beta 2 gene. Both elements differ only in
      the second half-motifs, in which the first and sixth position is occupied by
      thymidines (K13-RARE) instead of adenines (beta 2-RARE), as well as in their
      pentameric spacer sequences. Despite this striking homology in the receptor
      binding domains, we show by transfection of reporter gene constructs of the
      elements into primary fore-stomach keratinocytes and transformed epidermal cell
      lines that in both cell systems, unlike beta 2-RARE, the wild-type K13-RARE
      completely lacks transactivating properties in the presence of RA. A recent
      hypothesis proposes that aberrant gene expression during tumorigenesis may occur
      through conversion of inactive response elements with high homology to hormone
      response elements into functional enhancers by carcinogen-induced point mutations
      at critical positions (Nawaz et al., Mol. Carcinogen., 7, 76-82, 1993). To
      investigate whether the aberrantly expressed K13 gene falls into the category of
      those genes, reporter gene constructs of K13-RARE variants in which either the
      initial or the terminal thymidine of the second half-motif was replaced by
      adenine were transfected into epidermal cell lines. Neither mutant exhibited RA
      dependent transactivating properties. Strong transactivation could only be
      achieved by a K13-RARE mutant in which both critical thymidines were substituted
      by adenines. This type of closely spaced base exchange, unlikely to be created
      during DMBA initiation of mouse epidermis, was not detectable on sequencing
      genomic DNA of a squamous cell carcinoma and a transformed epidermal cell line.
      Instead, in both cases, only the wild-type K13-RARE could be demonstrated. A
      regulatory role of this RARE-like sequence in the promoter of the murine K13 gene
      for both normal and aberrant expression of the gene can therefore be excluded.

PMID- 7525099
TI  - Regulation of nitric oxide synthase and soluble guanylyl cyclase.

PMID- 7525100
TI  - Histo- and cytochemistry of guanylate cyclase and nitric oxide synthase: a
      critical appraisal.

PMID- 7525101
TI  - Wave-front curvature as a cause of slow conduction and block in isolated cardiac
      muscle.
AB  - We have investigated the role of wave-front curvature on propagation by following
      the wave front that was diffracted through a narrow isthmus created in a two
      dimensional ionic model (Luo-Rudy) of ventricular muscle and in a thin (0.5-mm)
      sheet of sheep ventricular epicardial muscle. The electrical activity in the
      experimental preparations was imaged by using a high-resolution video camera that
      monitored the changes in fluorescence of the potentiometric dye di-4-ANEPPS on
      the surface of the tissue. Isthmuses were created both parallel and perpendicular
      to the fiber orientation. In both numerical and biological experiments, when a
      planar wave front reached the isthmus, it was diffracted to an elliptical wave
      front whose pronounced curvature was very similar to that of a wave front
      initiated by point stimulation. In addition, the velocity of propagation was
      reduced in relation to that of the original planar wave. Furthermore, as shown by
      the numerical results, wave-front curvature changed as a function of the distance
      from the isthmus. Such changes in local curvature were accompanied by
      corresponding changes in velocity of propagation. In the model, the critical
      isthmus width was 200 microns for longitudinal propagation and 600 microns for
      transverse propagation of a single planar wave initiated proximal to the isthmus.
      In the experiments, propagation depended on the width of the isthmus for a fixed
      stimulation frequency. Propagation through an isthmus of fixed width was rate
      dependent both along and across fibers. Thus, the critical isthmus width for
      propagation was estimated in both directions for different frequencies of
      stimulation. In the longitudinal direction, for cycle lengths between 200 and 500
      milliseconds, the critical width was < 1 mm; for 150 milliseconds, it was
      estimated to be between 1.3 and 2 mm; and for the maximum frequency of
      stimulation (117 +/- 15 milliseconds), it was > 2.5 mm. In the transverse
      direction, critical width was between 1.78 and 2.32 mm for a basic cycle length
      of 200 milliseconds. It increased to values between 2.46 and 3.53 mm for a basic
      cycle length of 150 milliseconds. The overall results demonstrate that the
      curvature of the wave front plays an important role in propagation in two
      dimensional cardiac muscle and that changes in curvature may cause slow
      conduction or block.

PMID- 7525102
TI  - Surface staining and cytotoxic activity of heat-shock protein 60 antibody in
      stressed aortic endothelial cells.
AB  - Heat-shock protein (hsp) expression can be induced by high temperature, exposure
      to cytokines or oxygen radicals, ischemia, hemodynamic overload, or viral
      infections. To determine whether surface expression of hsp60 occurs in aortic
      endothelial cells stressed by high temperature or cytokines, cells from rat
      aortas were cultivated and stained with several types of monoclonal antibodies
      against hsp60. Other antibodies, eg, those against intercellular adhesion
      molecule-1 (ICAM-1), or immune response-associated antigens were also used as
      controls. Positive staining of endothelial cells on the surface and in the
      cytoplasm was observed after pretreatment of the cells with cytokine-containing
      medium, tumor necrosis factor-alpha (TNF-alpha), or interleukin-1 alpha and
      labeling with a specific monoclonal antibody against hsp60 (II-13). Fluorescence
      activated cell sorter analyses showed that over 80% of living endothelial cells
      stressed by cytokine-containing medium, by TNF-alpha, or at 42 degrees C, but not
      by interleukin-1 alpha, were positively surface stained with this antibody.
      Increased intensity of immunostaining with antibodies to ICAM-1 and immune
      response-associated antigen was also seen on the cytokine-stressed endothelial
      cells. Furthermore, when TNF-alpha stimulated endothelial cells labeled with 51Cr
      were incubated with antibody II-13 in the presence of complement, significant
      lysis occurred. In summary, endothelial cells stressed by high temperature or
      certain cytokines, eg, TNF-alpha, express hsp60 in the cytoplasm and on their
      surfaces, and these cells were susceptible to complement-dependent lysis by hsp60
      specific antibody. These observations may be significant for elucidating the
      mechanisms of the involvement of immune reactions to hsp65/60 in initiating
      atherosclerosis.

PMID- 7525104
TI  - Growth-promoting effects of substance P on endothelial cells in vitro. Synergism
      with calcitonin gene-related peptide, insulin, and plasma factors.
AB  - The purpose of this study was to determine the effects of the vasoactive
      perivascular neuropeptide substance P (SP) on the growth and function of vascular
      endothelial cells in serum-free culture conditions with cells quiescent in the G0
      G1 phase of the cell cycle and to characterize the response. In addition,
      interactions between SP and other growth factors and neuropeptides including
      insulin, platelet factors, neurokinin A, neurokinin B, and calcitonin gene
      related peptide (CGRP) were studied on endothelial cell growth and compared.
      Growth effects were determined by stimulation of tritiated thymidine
      incorporation into DNA and cell proliferation. SP exhibited differential effects
      on cell growth that were a function of concentration, incubation time,
      interaction with other growth factors, and cell culture conditions. DNA synthesis
      in response to SP showed a bell-shaped distribution with a maximal effect that
      was 10.5-fold over control at 500 micrograms/mL of SP after 48 hours of
      incubation. The effect showed marked synergism with insulin (10 micrograms/mL)
      and with CGRP (0.01 to 10 micrograms/mL), which is colocalized with SP in vivo.
      Insulin and CGRP alone had no significant effect on endothelial cell growth.
      Furthermore, no synergism was observed between SP and platelet-derived growth
      factor or platelet-derived endothelial cell growth factor. Endothelial cell
      proliferation increased in response to SP to 2.6-fold over control at 48 hours,
      was maximal at 10 micrograms/mL SP, and also demonstrated synergism with insulin
      (10 micrograms/mL). Our studies indicate that neuropeptides play a significant
      role in regulating endothelial cell growth and proliferation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7525103
TI  - Role of nitric oxide in the regulation of oxygen consumption in conscious dogs.
AB  - The role of nitric oxide (NO) in the regulation of O2 consumption was studied in
      chronically instrumented conscious dogs. A specific NO synthesis inhibitor, nitro
      L-arginine (NLA, 30 mg/kg i.v.), significantly increased mean arterial pressure
      from 100 +/- 4 to 134 +/- 5 mm Hg (mean +/- SEM) and total peripheral resistance
      by 157 +/- 16% and reduced cardiac output by 47 +/- 3% and heart rate by 34 +/-
      6% after 120 minutes. Changes in arterial blood gases were not observed. There
      were significant changes in PO2 (-14 +/- 2 mm Hg), O2 saturation (-21 +/- 2%),
      the percentage of hemoglobin as oxyhemoglobin (-21 +/- 2%), and O2 content (-3.0
      +/- 0.9 vol%) and a significant increase in percent reduced hemoglobin (21 +/-
      1%) in mixed venous blood, associated with an increase in O2 extraction (5.1 +/-
      0.2 vol%) (all P < .01). O2 consumption was increased from 124 +/- 6 to 155 +/- 9
      mL/min (P < .05). Methoxamine, titrated to have hemodynamic effects similar to
      those of NLA (eg, mean arterial pressure increased from 97 +/- 4 to 131 +/- 5 mm
      Hg), had much smaller effects on venous blood gases, hemoglobin, and O2
      extraction (2.3 +/- 0.7 vol%) and no significant effect on O2 consumption. NLA
      also caused an increase in O2 consumption of 37 +/- 8% (P < .01) in quietly
      resting conscious dogs that had undergone pretreatment with hexamethonium and
      atropine, but no significant change in O2 consumption in dogs anesthetized with
      barbiturate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525106
TI  - [Analysis of the target epitopes recognized by two monoclonal antibodies directed
      to egg-associated fractions of Schistosoma japonicum].
AB  - Two IgM isotype monoclonal antibodies (McAb), 2H10 and 2H1, recognizing
      repetitive epitopes on Schistosoma egg-associated molecules were characterized
      and their specificities were identified in a two-site sandwich ELISA system. In
      consistent with the differences in immunological behaviour and specificity
      demonstrated with immunoelectrophoresis (IEP) and immunofluorescent antibody
      (IFA) techniques, absolutely negative reactions found in the heterologous
      detecting system with alternated capture and detecting McAbs of the two revealed
      a complete incompatibility giving evidences that epitopes on different molecules
      were recognized. Immunological liability of the target antigen SEA or SEA-TCA to
      the two McAbs were demonstrated on sodium periodate and trifluoroacetic acid
      treatment indicating the biochemical nature of these epitopes were glycosyolated
      molecules with apparently higher resistance to the oxidizing agent showing in
      2H10 recognizing epitopes. By means of an ion-gradient Mono-Q FPLC system
      (Pharmacia), 2H10-reactive epitopes of SEA, being tested not so efficiently
      adsorbed by ConA-sepharose affinity column, was found successfully concentrated
      in the profile eluted with pH 8.0 PBS at 0.2-0.4 NaCl ionic strength. Repeated
      trials on SDS-PAGE and Western blotting analysis with the reactive fractions
      further showed a heterogeneity of molecular weight range as well as the non
      transferable property of the CHO-reactive groups.

PMID- 7525105
TI  - E-selectin ligands mediate tumor necrosis factor-induced neutrophil sequestration
      and pulmonary edema in guinea pig lungs.
AB  - We have previously shown in perfused guinea pig lungs that tumor necrosis factor
      alpha (TNF-alpha) pretreatment of lungs enhanced neutrophil sequestration as
      reflected by a 2.4-fold increase in lung myeloperoxidase (MPO) activity.
      Subsequent perfusion of phorbol 12-myristate 13-acetate (PMA) to activate the
      sequestered neutrophils produced an approximately threefold increase in the
      pulmonary capillary hydrostatic pressure and fulminant pulmonary edema. Using
      this ex vivo model of lung injury, we studied the role of three putative E
      selectin ligands, sialyl-Lewis X, Lewis X, and dimeric sialyl-Lewis X, in
      mediating neutrophil sequestration and pulmonary edema. We pretreated neutrophils
      with monoclonal antibodies (mAbs) directed against these E-selectin ligands.
      Pretreatment of neutrophils with mAbs to sialyl-Lewis X and Lewis X reduced the
      neutrophil sequestration, as evidenced by 45% and 27% reductions in MPO activity
      from control levels, respectively. This occurred in parallel with inhibition of
      neutrophil adhesion to the TNF-alpha-activated endothelial cells in vitro. The
      mAbs to dimeric sialyl-Lewis X and an isotype-matched control mAb against
      lactosamines present on neutrophils had no effect on lung MPO activity and
      neutrophil adhesion. All mAbs to sialyl-Lewis X, Lewis X, and dimeric sialyl
      Lewis X reduced the increases in the pulmonary capillary hydrostatic pressure
      after challenge of the sequestered neutrophils with PMA and also reduced lung
      weight gain by 71%, 45% and 38%, respectively. The control mAb to the
      lactosamines had no effect on the pulmonary capillary hydrostatic pressure and
      lung weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525107
TI  - A novel sialyl LewisX analog attenuates neutrophil accumulation and myocardial
      necrosis after ischemia and reperfusion.
AB  - BACKGROUND: Polymorphonuclear leukocytes (PMNs) have been shown to mediate
      coronary vascular and myocardial tissue injury after coronary artery ischemia and
      reperfusion. Previous studies using specific monoclonal antibodies directed
      against P-selectin and L-selectin have demonstrated the involvement of the
      selectin family of glycoproteins in the early phase of PMN-induced myocardial
      ischemia-reperfusion injury. We examined the effects of a novel oligosaccharide
      analog of sialyl LewisX (SLeX), which blocks both P-selectin and E-selectin in an
      acute canine model of myocardial ischemia and reperfusion. METHODS AND RESULTS:
      Anesthetized, open-chest dogs were subjected to 1.5 hours of left circumflex
      coronary artery (LCx) occlusion followed by 4.5 hours of reperfusion and randomly
      received the SLeX analog CY-1503 (5 mg/kg IV), the nonfucosylated analog of CY
      1503, SLN (5 mg/kg IV), or saline 5 minutes before reperfusion. The investigators
      were blinded to the treatment until all the data analysis was completed. All
      three groups of dogs exhibited similar and severe reductions in transmural
      myocardial blood flow in the LCx region as well as pronounced myocardial
      contractile dysfunction during occlusion, suggesting comparable degrees of
      myocardial ischemia. After reperfusion, dogs receiving saline (n = 6) displayed
      an enhanced degree of myocardial injury that was evidenced by a dramatic
      elevation in plasma creatine kinase (CK) activity, PMN accumulation, and
      myocardial necrosis. Plasma CK activity increased from 1.9 +/- 0.5 IU/microgram
      protein at baseline to 73.0 +/- 11.0 IU/micrograms protein (P < .001) at 4.5
      hours of reperfusion and myocardial PMN accumulation, as measured by cardiac
      myeloperoxidase (MPO) activity, and was significantly enhanced (P < .01) within
      the necrotic zone compared with the nonischemic zone (4.3 +/- 0.6 versus 0.7 +/-
      0.1 U/100 mg tissue). After 4.5 hours of reperfusion, 36% of the myocardium
      within the ischemic zone and 17% of the left ventricle became necrotic in the
      dogs receiving saline. Treatment with CY-1503 (n = 6) significantly (P < .05)
      blunted plasma CK activity by more than 50% throughout the reperfusion period,
      reduced necrotic zone PMN accumulation by 63% (P < .05), and reduced myocardial
      necrosis in the area at risk by 65% (P < .01) and by 72% within the left
      ventricle (P < .01). In contrast, administration of the nonfucosylated analog of
      CY-1503, SLN (n = 6), failed to exert any detectable cardioprotective effects
      after myocardial ischemia and reperfusion. CONCLUSIONS: Our results provide
      strong evidence that treatment with a unique carbohydrate analog of SLeX, CY
      1503, significantly reduces the degree of myocardial injury associated with
      coronary artery ischemia and reperfusion. The profound cardioprotection appears
      to be related to a reduction in PMN accumulation within the ischemic-reperfused
      myocardium. Additional studies investigating more-prolonged periods of
      reperfusion are required to determine whether CY-1503 treatment merely delays the
      onset or actually reduces the full extent of myocardial necrosis after ischemia
      and reperfusion.

PMID- 7525109
TI  - Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery
      spasm in a swine model.
AB  - BACKGROUND: The intracellular mechanism of coronary artery spasm is still
      unknown. The pathway mediated by protein kinase C (PKC) is an important
      intracellular process of various cellular responses, including vascular smooth
      muscle contraction. Thus, we examined the role of the PKC-mediated pathway in the
      pathogenesis of coronary artery spasm in our in vivo swine model. METHODS AND
      RESULTS: Seven Gottingen miniature pigs underwent coronary balloon injury and x
      ray irradiation to induce atherosclerotic lesion. After 6 to 18 months,
      intracoronary serotonin (3 micrograms/kg) or histamine (3 micrograms/kg)
      repeatedly induced coronary artery spasm at the atherosclerotic site. At the
      spastic site, intracoronary administration of phorbol-12,13-dibutyrate (PDBu)
      (10(-9) mol/kg), a PKC-activating phorbol ester, also induced coronary artery
      spasm, which was completely blocked by pretreatment with intracoronary
      staurosporine (10 micrograms/kg), a PKC inhibitor. Intracoronary administration
      of an inactive phorbol ester, phorbol-12,13-didecanoate (10(-9) mol/kg), did not
      induce coronary vasoconstriction. Coronary artery spasm induced by the autacoids
      was significantly augmented by pretreatment with intracoronary PDBu and partially
      inhibited by staurosporine. Intracoronary administration of Bay K 8644 (10
      micrograms/kg), a dihydropyridine-sensitive L-type calcium channel agonist, also
      induced coronary artery spasm at the spastic site, which was significantly
      inhibited by pretreatment with intracoronary staurosporine or nifedipine (0.1
      mg/kg). CONCLUSIONS: These results suggest (1) the PKC-mediated pathway is
      importantly involved in the pathogenesis of coronary artery spasm, (2) activation
      of the PKC-mediated pathway partially accounts for serotonin- and histamine
      induced coronary artery spasm, and (3) at the spastic site, calcium influx
      through dihydropyridine-sensitive L-type calcium channel and/or calcium
      sensitivity of the contractile proteins may be augmented by the PKC-mediated
      pathway.

PMID- 7525110
TI  - Surgical alternatives to the Fontan procedure incorporating a hypoplastic right
      ventricle.
AB  - BACKGROUND: Frequently the definitive operation for patients with a right
      ventricle (RV) that is too small to support full cardiac output is a modified
      Fontan operation. However, other surgical options exist that incorporate a small
      RV in the atriopulmonary pathway when biventricular repair is not feasible
      because of RV or tricuspid valve hypoplasia. The risks and benefits of these
      options have not been well defined. METHODS AND RESULTS: Between 1988 and 1993, 8
      patients (6 with pulmonary atresia and intact ventricular septum and 2 with
      tricuspid valve stenosis and RV hypoplasia) underwent a cavopulmonary connection,
      which allowed right atrial blood to flow either to the pulmonary artery via the
      RV or directly via the cavopulmonary anastomosis. Age at surgery ranged from 1.5
      to 9 years. The proximal right pulmonary artery was ligated in 5 patients, and
      the atrial septal defect was closed during the same procedure in 7 of the 8
      patients. The echocardiographic right ventricular-left ventricular volume ratio
      ranged from 9% to 25%, and tricuspid valve z-scores ranged from 0 to -4. There
      were no deaths at a median follow-up of 24 months (range, 7 to 61 months). Mild
      exertional limitation was evident in only one patient. Postoperative
      echocardiograms demonstrated pulsatile systolic flow across the RV outflow tract
      in 5 patients and low-velocity diastolic-systolic flow in a sixth patient with
      extreme tricuspid valve hypoplasia. At postoperative cardiac catheterization (6
      patients) right atrial mean pressures ranged from 7 to 13 mm Hg and mixed venous
      saturations from 62% to 70%. CONCLUSIONS: Right atrial decompression via a
      superior vena cava-to-pulmonary artery anastomosis allows incorporation of a
      small RV into the pulmonary circulation and closure of the atrial septum, with
      excellent results to date.

PMID- 7525112
TI  - Developmental alterations in NMDA receptor-mediated [Ca2+]i elevation in
      substantia gelatinosa neurons of neonatal rat spinal cord.
AB  - Using spinal cord slices prepared from neonatal rats, the intracellular free Ca2+
      concentration ([Ca2+]i) in neurons located in the dorsal horn substantia
      gelatinosa (SG) was measured with microscopic fluorometry by loading fura 2-AM
      into neurons. Developmental alterations in the elevation of [Ca2+]i elicited by
      the glutamate analogs, NMDA and AMPA, were investigated from postnatal day (PNDs)
      1 to 17. During the 1st week of postnatal life, when neuronal maturation of the
      SG is known to take place, the NMDA response remained large or even slightly
      increased. It subsequently showed a gradual decline. This pattern of postnatal
      changes is consistent with previously reported autoradiographic studies on NMDA
      binding sites. The affinity of receptors for NMDA was found to decrease
      constantly during the period examined. The AMPA response and resting [Ca2+]i
      showed no significant developmental changes. Neonatal treatment with capsaicin,
      which has been shown to degenerate fine primary afferent fibers terminating in
      the SG, delayed the developmental decline in the NMDA-induced [Ca2+]i response.
      It is suggested that the number and the molecular properties of NMDA receptors
      expressed in the SG change during early postnatal neuronal maturation. The
      temporal coincidence between postnatal alteration in NMDA-induced [Ca2+]i
      elevation and neuronal maturation of the SG may indicate that intracellular Ca2+
      regulated by NMDA receptor activation is related to postnatal neuronal
      maturation. Activation of fine primary afferent fibers may contribute to the
      observed developmental alterations in the NMDA response of SG neurons.

PMID- 7525108
TI  - Direct in vivo gene transfer into porcine myocardium using replication-deficient
      adenoviral vectors.
AB  - BACKGROUND: Efficient methods of introducing genes into myocardial cells must be
      developed before local somatic cell gene therapy can be implemented against
      myocardial disease. Although adenoviral (Ad5) vectors have been used to target
      rodent hearts and plasmid DNA has been directly injected into the myocardium of
      rats and dogs, the amounts of recombinant protein produced by these procedures
      have not been reported, and adenoviral vectors have not been used in large
      mammalian hearts. METHODS AND RESULTS: Replication-deficient recombinant
      adenoviral vectors carrying either the luciferase or lacZ reporter genes were
      injected directly into the ventricular myocardium of adult domestic swine for
      evaluation of reporter gene expression. This procedure did not affect regional
      myocardial function as assessed by systolic wall thickening using ultrasonic
      crystals. Luciferase activity was detected 3 days after injection, increased
      markedly at 7 days, and then declined progressively at 14 and 21 days. Luciferase
      production was comparable in the right and left ventricular walls and increased
      with increasing amounts of virus, reaching 61 +/- 21 ng at the highest dose
      examined (3.6 x 10(9) plaque-forming units). The injection of 200 micrograms of
      plasmid DNA (pRSVL) produced levels of luciferase comparable to 1.8 x 10(8)
      plaque-forming units of recombinant Ad5; however, when normalized to the number
      of genes injected, the adenovirus was 140,000 times more efficient than plasmid
      DNA. Histochemical analysis of beta-galactosidase activity produced by a second
      Ad5 vector demonstrated that nearly all (> 95%) of the stained cells were
      cardiomyocytes and that the percentage of cardiomyocytes infected by the virus
      could be quite high in microscopic regions adjacent to the needle track (up to
      75% in fields of 60 to 70 cells); however, Ad5-infected cells were rarely
      observed farther than 5 mm from the injection site. Furthermore, the Ad5 vector
      induced pronounced leukocytic infiltration that was far in excess of that seen
      after injection of vehicle alone. CONCLUSIONS: This study demonstrates for the
      first time that direct intramyocardial injection of replication-deficient
      adenovirus can program recombinant gene expression in the cardiomyocytes of a
      large animal species with relevance to human physiology. The efficiency of
      adenovirus-mediated gene transfer is far superior to that of plasmid DNA
      injection, and this method appears to be capable of producing more recombinant
      protein. However, the cell-mediated immune response to the Ad5 vector and the
      limited distribution of reporter gene expression suggest that less immunogenic
      recombinant vectors and more homogeneous administration methods will be required
      before Ad5 vectors can be successfully used for phenotypic modulation.

PMID- 7525111
TI  - Intramuscular administration of vascular endothelial growth factor induces dose
      dependent collateral artery augmentation in a rabbit model of chronic limb
      ischemia.
AB  - BACKGROUND: Despite major advances in both surgical and percutaneous
      revascularization techniques, limb salvage and relief of ischemic pain cannot be
      achieved in many patients with diffuse peripheral vascular disease. Vascular
      endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific
      mitogen. Previous studies have suggested that VEGF is a regulator of naturally
      occurring physiological and pathological angiogenesis. In this study, the
      therapeutic potential of intramuscularly administered VEGF was investigated in a
      rabbit model of chronic hindlimb ischemia. METHODS AND RESULTS: Ischemia was
      induced in the hindlimb of 24 New Zealand White rabbits by ligation of the distal
      external iliac artery and complete excision of the femoral artery. Ten days after
      the induction of limb ischemia (day 0), saline (group A, n = 7) or the 165-amino
      acid isoform of recombinant human VEGF (group B: 200 micrograms, n = 6; group C:
      500 micrograms, n = 7; group D: 1000 micrograms, n = 4) was administered
      intramuscularly into the ischemic limb daily for 10 days. Angiography on day 30
      after initiation of therapy revealed statistically significant dose-dependent
      augmentation of collateral vessels in the ischemic limb (angiographic score:
      group A, 13.0 +/- 1.1; group B, 21.2 +/- 1.8; group C, 27.3 +/- 1.4; group D,
      31.5 +/- 2.5). Capillary density in the thigh muscles on day 30 was 1.6 times
      greater in VEGF groups versus controls (176 +/- 15.3 versus 113 +/- 27.3 per
      square millimeter, P < .05). Amelioration of the hemodynamic deficit in the
      ischemic limb was documented by calf systolic blood pressure ratio (group A, 0.52
      +/- 0.02; group B, 0.67 +/- 0.02; group C, 0.73 +/- 0.01; group D, 0.82 +/-
      0.03). "Clinical" improvement (incidence of calf muscle atrophy and distal limb
      necrosis: group A, 85.7%; group B, 33.3%; group C, 14.3%; group D, 0%) was
      greater in VEGF-treated than in control animals, again in a dose-dependent
      fashion. CONCLUSIONS: These findings demonstrate a significant dose-dependent
      augmentation in limb perfusion accompanied by evidence of increased collateral
      formation after intramuscular administration of VEGF in ischemic rabbit
      hindlimbs. This study thus supports the hypothesis that administration of VEGF to
      stimulate angiogenesis may represent a new therapeutic modality in the management
      of arterial insufficiency.

PMID- 7525113
TI  - Neonatal handling alters serotonin (5-HT) turnover and 5-HT2 receptor binding in
      selected brain regions: relationship to the handling effect on glucocorticoid
      receptor expression.
AB  - Neonatal handling permanently alters hypothalamic-pituitary-adrenal responses to
      stress. This effect is, in part, mediated by a handling-induced increase in
      forebrain glucocorticoid receptor gene expression. The effect of postnatal
      handling on glucocorticoid receptor expression appears to be mediated by an
      increase in serotonin (5-HT) activity, acting via a 5-HT2 receptor with a high
      affinity for 5-HT (i.e. the 5-HT2H receptor). In the present study we examined
      the nature of the effects of handling on the relevant 5-HT systems. We found
      that: (1) handling increases 5-HT turnover in regions of the neonatal rat brain
      where glucocorticoid receptor expression is altered (i.e. the hippocampus and
      frontal cortex), but not in regions where glucocorticoid receptor expression in
      unaffected (e.g. hypothalamus and amygdala); (2) handling has no long-term
      effects on hippocampal or frontal cortex 5-HT turnover, and is actually
      associated with a decrease in 5-HT concentrations; and (3) handling does not
      alter 5-HT2 receptor density in the hippocampus or frontal cortex in neonates
      (although there are surprising effects on 5-HT2 receptor density in the frontal
      cortex of adult animals). Taken together these data provide further evidence for
      the importance of 5-HT in mediating the effects of handling on the development of
      glucocorticoid receptor expression, but suggest that the role of 5-HT is unique
      to early development; differences in glucocorticoid receptor expression in adult
      handled and non-handled animals are not associated with long-term differences in
      either 5-HT levels or 5-HT2 receptors.

PMID- 7525115
TI  - Chronic NMDA receptor blockade or muscimol inhibition of cerebellar cortical
      neuronal activity alters the development of spinocerebellar afferent topography.
AB  - The requirement for cerebellar cortical neuronal activity in the development of
      spinocerebellar afferent topography was investigated in neonatal rats. In adult
      rats lower thoracic-upper lumbar spinocerebellar projections are localized to
      sharply circumscribed patches in the granule cell layer of the cerebellar
      anterior lobe. In transverse sections these patches appear as sagittally oriented
      stripes. This pattern develops postnatally as many spinal axons which initially
      project between the incipient stripes are eliminated thereby sharpening the
      stripe boundaries. We attempted to alter cerebellar cortical neuronal activity in
      neonatal animals to study the effects of these changes on the development of
      spinocerebellar stripes. In some experiments glutaminergic excitatory synaptic
      transmission was chronically blocked with the N-methyl-D-aspartate (NMDA)
      receptor antagonist 2-aminophosphovaleric acid (APV). In other experiments
      postsynaptic activity was directly inhibited by the gamma-aminobutyric acid
      agonist muscimol. Chronic exposure to APV or to muscimol did not affect the
      initial development of spinocerebellar projections; many spinal axons were
      present in the anterior lobe and arranged in incipient stripes. Both the APV and
      the muscimol appeared to prevent the elimination of interstripe projections;
      consequently the boundaries of the stripes remained poorly defined. These
      findings suggest that cerebellar cortical neuronal activity is a necessary
      requirement for the refinement of spinal afferent topography in the anterior
      lobe.

PMID- 7525116
TI  - Variance function as basis for assessment of test performance: methodological
      studies with two assays of prostate-specific antigen.
AB  - We evaluated the usefulness of a recently described procedure to assess the
      analytical performance of an assay. To demonstrate the advantages of this
      approach, we compared the performance of two analytical systems for determining
      prostate-specific antigen (PSA). Triplicate measurements of PSA with the IMx
      (Abbott) and the ACS 180 (Ciba Corning) were used to calculate the variance
      function. This function was the basis for the derivation of the critical limit
      (LC), the limit of detection (LD), the power of definition (PD), and the lower
      limit of the quantification interval. The standard deviation of the blank was
      extrapolated by means of the variance function. LC was calculated as the
      concentration at which the normal distribution of the blank intersects an
      adjacent normal distribution (with a defined overlap, e.g., 5%). The mean of the
      adjacent normal distribution represents the LD. The PD is a new mathematical
      approach to describe the analytical sensitivity of an assay in different ranges
      of the quantification interval. The procedure is statistically well defined and
      allows one to obtain the data on the test performance directly from patients'
      samples, without artificial zero controls. Therefore, use of the variance
      function could be a general model for the assessment of the analytical
      performance of an assay.

PMID- 7525117
TI  - Separation of alkaline phosphatase isoforms with and without intact glycan
      phosphatidylinositol anchors in aqueous polymer phase systems.
AB  - Alkaline phosphatase (ALP) isoforms can be distinguished from each other by their
      partition characteristics in aqueous two-phase systems composed of water-soluble
      polymers, the phases of which are differentially sensitive to the presence of
      glycan-phosphatidylinositol anchors. Compared with detergent-based systems, the
      aqueous polymer systems have the advantage that micelle formation does not take
      place. Partition of anchor-intact and anchor-degraded molecules in the latter
      systems is further improved by attachment of a hydrophobic ligand to one of the
      phase forming polymers. In this way, anchor-intact molecules can be separated
      from molecules with degraded anchors in a single partition step. The method has
      been used to confirm that ALP in human serum is predominantly anchor degraded,
      whereas in bile it retains its anchor intact.

PMID- 7525114
TI  - Growth factor effects on the proliferation of different retinal glial cells in
      vitro.
AB  - Vascularized mammalian retinae contain two distinct neuroglial cells types,
      radially oriented Muller cells and astrocytes, which are located in the nerve
      fiber layer. These cell types derive from different precursor cells and
      proliferate during ontogenesis at distinct schedules. The aim of the present
      study was to disclose whether growth factors, which are known to interfere with
      the development of neuroglial cells in the central nervous system, like basic and
      acidic fibroblast growth factor (aFGF and bFGF), epidermal growth factor (EGF)
      and platelet-derived growth factor, have similar or distinct effects on the
      proliferative capacity of retinal astrocytes and Muller cells. These questions
      were tested by applying growth factors to cultured astrocytes and Muller cells
      from early postnatal rabbit retina. Proliferating cells were identified by double
      labeling experiments combining cell type specific markers with bromodeoxyuridine
      immunocytochemistry and [3H]thymidine incorporation experiments, respectively. In
      addition, we used the anatomical advantage of the rabbit retina. Its peripheral
      part is astroglial cell-free. Cultures prepared from this part of the retina (P
      cultures) contain Muller cells, microglial cells and neurons, while cultures from
      the 'central part', the medullary rays (MR) region contain, in addition,
      astrocytes and oligodendrocytes. Our studies show that Muller cell proliferation
      is stimulated by EGF in a dose dependent manner, while astrocyte proliferation is
      stimulated by aFGF and bFGF. The proliferation of O4-positive glial precursor
      cells is stimulated by aFGF, bFGF and platelet-derived growth factor, but not by
      EGF. Microglial cells, which are a minor population in these cultures, do not
      respond to either of these factors.

PMID- 7525118
TI  - Relationships between ulinastatin and alpha-1-microglobulin in human urine.

PMID- 7525119
TI  - Biological markers and ovarian carcinomas: galactosyltransferase, CA 125,
      isoenzymes of amylase and alkaline phosphatase.
AB  - We present a comparative study of several biological markers
      (galactosyltransferase, CA 125, isoenzymes of amylase and alkaline phosphatase)
      with a view to ovarian carcinoma follow-up. Serum samples were obtained from a
      population of 75 patients under clinical observation. After a minimum 18-months
      period, we assessed the prognostic value of the markers. No marker permits the
      detection of discrete, evolving carcinomas. CA 125 is the marker that gives the
      best results, particularly in terms of sensitivity. Galactosyltransferase has a
      lower sensitivity except in the case of endometrioid carcinomas. Simultaneous
      analysis with CA 125 and galactosyltransferase results in no decisive
      improvement, other than greater precision in unfavourable prognoses. Isoenzymes
      of amylase and alkaline phosphatase are of no interest in the follow-up of such
      carcinomas.

PMID- 7525120
TI  - Metabolic effects of growth hormone administered subcutaneously once or twice
      daily to growth hormone deficient adults.
AB  - OBJECTIVE: The aim of this study was to compare the metabolic effects of GH
      administered subcutaneously either once or twice daily. The actions of GH might
      depend upon a pulsatile pattern of serum GH. Pulsatile and continuous intravenous
      delivery of GH, however, induce similar short-term metabolic effects in GH
      deficient patients. An improved growth response is obtained in GH deficient
      children when a fixed weekly GH dose is administered by daily subcutaneous
      injections instead of twice or thrice-weekly intramuscular injections. A more
      pulsatile pattern and serum GH levels above zero might be achieved by further
      increasing the injection frequency. Increased daytime GH levels might, however,
      adversely affect the circadian patterns of metabolic indices, which have been
      demonstrated to be more successfully reproduced by evening compared with morning
      GH administration. DESIGN AND MEASUREMENTS: In a cross-over study, 8 GH deficient
      patients (age 16-43 years) were treated with 3 IU/m2/24 h of human GH. The dose
      was injected in the evening for 4 weeks and for another 4 weeks two-thirds was
      injected in the evening and one-third in the morning. At the end of each period
      the patients were admitted to the hospital for 37 hours. Steady-state profiles of
      GH, IGF-I, IGF binding proteins 1 and 3, insulin, glucose, lipid intermediates
      and metabolites were obtained following administration of 3 IU/m2 of GH (at 1900
      h (one injection) and at 1900 and 0800 h (two injections)). RESULTS: Similar mean
      integrated levels of serum GH (mU/l) were obtained (7.46 +/- 0.84 (one injection)
      vs 6.46 +/- 0.62 (two injections) (P = 0.15)). Mean levels +/- SEM of serum IGF-I
      (micrograms/l) were significantly increased (P < 0.01) following two daily GH
      injections (330.3 +/- 48.1 (one injection) vs 399.1 +/- 53.0 (two injections)).
      Serum IGFBP-3 levels were not significantly different on the two occasions, while
      levels of the GH independent IGFBP-1 (micrograms/l) were slightly but
      significantly lower following twice-daily GH injections (1.61 +/- 0.42 vs 1.13 +/
      0.56, respectively (P < 0.04)). The pattern of IGFBP-1 was opposite to that of
      insulin. Similar levels of insulin and glucose were obtained with both GH
      regimens, while levels of non-esterified fatty acids were significantly higher
      following once-daily GH injection (P < 0.001). CONCLUSIONS: Twice-daily GH
      injections, apart from producing a more physiological serum GH profile, were
      superior to one injection in increasing serum IGF-I and decreasing IGFBP-1
      levels. Both of these changes tend to amplify the effects of the administered GH.
      Twice-daily injections, however, resulted in lower night-time levels of lipid
      intermediates.

PMID- 7525121
TI  - A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E
      21): beneficial effects of treatment with growth hormone and intrahepatic
      adriamycin.
AB  - We describe a case of recurrent hypoglycaemia associated with a hepatoma. During
      hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor
      II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF
      II (molecular weight 11 kDa) which probably represents a non-glycated form of pro
      IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both
      IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently
      described unextracted assay directed against the first 21 amino acids of the E
      domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct
      plasma estimation (plasma E-21) of larger molecular forms of IGF-II without
      interference from normal IGF-II and IGF binding proteins. Basal values were
      grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in
      the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM)
      before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and
      a reduction in hypoglycaemic attacks. The treatment was associated with a rise in
      IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment
      with the somatostatin analogue octreotide did not produce a significant change in
      plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic
      adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained
      normal and IGF-I increased. GH treatment was successfully withdrawn with no
      effect on plasma glucose or growth factor levels. The patient remained free from
      hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525122
TI  - Development and validation of a radioimmunoassay for follistatin in human serum.
AB  - OBJECTIVE: Follistatin (FS/FSH-suppressing protein/activin-binding protein) is a
      single-chain glycoprotein, structurally distinct from inhibin, that has been
      shown to have inhibin-like activity in suppressing FSH secretion both in vivo and
      in vitro. The aim of these studies was to develop and validate a radioimmunoassay
      (RIA) for FS in human serum, and to describe the physiological variations of
      serum FS in humans. PATIENTS: Serum was collected from normal men, and normal
      women in the follicular and luteal phases of the menstrual cycle. Clinical
      samples were also collected from male patients with hypogonadism, post-menopausal
      women and pregnant women in the first, second and third trimesters. MEASUREMENTS:
      A RIA for FS in human serum was developed using antisera raised against purified
      bovine FS and using bovine FS as tracer and standard. Serial dilutions of serum
      were non-parallel to purified bovine FS standard in the RIA. The addition of
      sodium dodecyl sulphate (SDS 0.05%) to the assay buffer resolved the non
      parallelism suggesting that the interference of serum in the RIA was an assay
      matrix effect. To characterize the serum FS immunoactivity further, serum was
      fractionated by gel filtration on Sephadex G-100. At neutral pH, FS
      immunoactivity eluted as a major peak in the molecular weight range > 200 kDa. In
      0.1 M HCl, a second peak of FS immunoactivity eluted in the molecular weight
      range 30-60 kDa consistent with the known sizes of FS. This suggested that FS was
      dissociating from a larger complex. Fractions taken from the low molecular weight
      region diluted in parallel with bovine FS in contrast with fractions from the
      high molecular weight region which were non-parallel. It is concluded that the
      non-parallelism of human serum in the FS RIA is due to the binding of serum FS to
      an unknown high molecular weight factor. This interference is eliminated by the
      inclusion of 0.05% SDS in the assay buffer. The RIA in 0.05% SDS has been applied
      to the description of the normal and pathophysiological variations of FS in human
      serum. RESULTS: There were no significant differences between FS levels in serum
      from hypogonadal men, normal women in the follicular phase of the menstrual
      cycle, post-menopausal women and pregnant women from the first, second and third
      trimesters. FS levels in serum of women in the luteal phase of the menstrual
      cycle were significantly lower than all other groups. FS levels in normal men
      were significantly higher than those in both luteal phase women and women in the
      first trimester of pregnancy (P < 0.05). CONCLUSIONS: These findings argue
      against a role for circulating follistatin in the control of gonadotrophin
      secretion and suggest that the gonads and/or conceptus are not the primary source
      of follistatin immunoactivity in serum. The lower follistatin levels in the
      luteal phase of the menstrual cycle remain unexplained.

PMID- 7525123
TI  - Inverse correlation between insulin-like growth factor binding protein-1 and
      insulin in patients with acromegaly during treatment with the somatostatin
      analogue octreotide.
AB  - OBJECTIVE: Previous reports have shown an inverse relation between IGFBP-1 and
      insulin levels in healthy men, patients with insulin dependent diabetes mellitus,
      and insulinoma. We have investigated whether this inverse relation also exists in
      acromegaly, before and during treatment with octreotide, and whether changes in
      IGFBP-1 levels relate to GH and IGF-I levels. DESIGN: We studied short-term
      treatment with octreotide in a double-blind placebo-controlled 14-day clinical
      trial. PATIENTS: Eighteen patients with acromegaly were studied. MEASUREMENTS:
      Plasma GH and serum IGFBP-1 levels were measured at hourly intervals from 0700 to
      1800 h before randomization (day 0) and on days 4, 6, 8, 14 and 20. Serum insulin
      was determined at 0700, 0800 and 0900 h, and serum IGF-I at 0700 h. RESULTS:
      Octreotide increased the daily mean IGFBP-1 level by 43% on day 8 and by 35% on
      day 14. The IGFBP-1 levels during octreotide were significantly higher (P < 0.05)
      compared to placebo, 29.9 +/- 3.9 vs 19.9 +/- 1.7 micrograms/l (mean +/- SEM) on
      day 8, and 28.3 +/- 3.2 vs 19.9 +/- 1.6 micrograms/l on day 14. Octreotide
      treatment significantly suppressed the insulin levels on all observation days by
      40-48% compared to placebo. There was a significant inverse correlation between
      IGFBP-1 levels and insulin levels, both before treatment and on the last day of
      treatment (r = 0.79, P = 0.04; r = -0.90, P = 0.02, respectively). GH and IGF-I
      were significantly decreased in the octreotide group compared to the placebo
      group during the entire treatment period. The mean of age related standard
      deviation scores of IGF-I in the octreotide group decreased from a pretreatment
      value of 6.47 +/- 0.74 to 3.60 +/- 1.20 on day 14. There was no significant
      correlation between IGFBP-1 levels and levels of GH and IGF-I, either before or
      during treatment. CONCLUSIONS: Octreotide treatment, in addition to reducing GH,
      IGF-I and insulin levels, is associated with an increase in IGFBP-1
      concentrations in patients with acromegaly, and it is suggested that the rise in
      serum IGFBP-1 is a consequence of the decrease in insulin secretion.

PMID- 7525126
TI  - Flagellate erythema after intraperitoneal bleomycin.

PMID- 7525125
TI  - Endocrine profiles during administration of the new non-steroidal anti-androgen
      Casodex in prostate cancer.
AB  - OBJECTIVE: Casodex (Zeneca) is a new potent, long-acting non-steroidal anti
      androgen, which produces androgen deprivation by blocking the androgen receptor.
      We evaluated the endocrine effects of Casodex 150 mg daily given in monotherapy
      as primary treatment for patients with prostate cancer. DESIGN: As part of a
      large, multicentre study comparing the therapeutic effects of surgical castration
      with 150 mg/day Casodex in monotherapy for patients with prostate cancer, a
      subgroup of 23 patients on Casodex were studied in detail for changes in
      endocrine parameters. Serum levels of LH, FSH, testosterone, DHT, oestradiol,
      prolactin, sex hormone binding globulin and free testosterone were measured at
      the start of therapy and after 1, 4, 8, 12 and 24 weeks. Effects on libido,
      sexual activity and the appearance of hot flushes, breast pain and gynaecomastia
      were recorded. RESULTS: Administration of Casodex resulted in a rise in LH levels
      in all patients with a mean increase after 24 weeks of 102% (P < 0.001). Mean FSH
      levels showed a limited increase (7%) after 24 weeks, which was significant only
      after 1 week (P < 0.001). As a result of the high LH levels, total testosterone
      levels increased after 24 weeks by 66% (P < 0.001), free testosterone by 57% (P <
      0.001) and dihydrotestosterone by 24% (P = 0.0112). Parallel to testosterone,
      oestradiol levels rose by a mean of 66% (P < 0.001). Mean sex hormone binding
      globulin and prolactin levels rose by respectively 8% (P = NS) and 65% (P <
      0.01). Despite an increase in testosterone levels, excellent androgen blockade
      was obtained, as shown by a decrease in prostate specific antigen levels in 22/23
      patients. Libido was maintained in 8/11 patients, and sexual activity in 5/6. No
      patient complained of hot flushes. However, mild gynaecomastia and/or breast
      tenderness were seen in 48 and 30% of cases respectively. CONCLUSION: Casodex 150
      mg/day monotherapy resembles surgical castration in achieving androgen
      deprivation, despite an increase in LH and testosterone levels. In contrast to
      castration, libido and sexual activity are usually maintained and hot flushes are
      rare. However, mild gynaecomastia and/or breast tenderness were noted in 48 and
      30% of patients.

PMID- 7525124
TI  - Effects of insulin-like growth factor-I on growth hormone and prolactin secretion
      and cell proliferation of human somatotrophinomas and prolactinomas in vitro.
AB  - OBJECTIVE: IGF-I inhibits GH secretion from normal and some tumorous pituitary
      tissue, and has been shown to be mitogenic for gonadotrophinoma cells in vitro.
      It is not known whether IGF-I affects somatotrophinoma cellular proliferation or
      the secretion of other hormones, such as PRL and alpha-subunit, which are often
      co-secreted by these tumours. We have therefore examined the effects of IGF-I on
      proliferation and hormonal secretion of human somatotrophinomas and prolactinomas
      in vitro. DESIGN: Pituitary adenoma tissue was dispersed to single cells in
      monolayer culture. The effects of 100 nM IGF-I on GH, PRL and alpha-subunit
      secretion were determined over 4-hour and over 4-day periods, and a 4-day dose
      response study using 1-100 nM IGF-I was performed on two tumours. Adenoma cell S
      phase proliferation was determined after bromodeoxyuridine incorporation for 1
      hour after 4 days, using a double immunostaining method. RESULTS: Over 4 hours,
      100 nM IGF-I had no effect on GH, PRL or alpha-subunit secretion in 7 tumours.
      Over 4 days, 100 nM IGF-I reduced GH secretion in 5/8 somatotrophinomas (range 17
      84%, P < 0.05) compared to controls, with tumours responding to IGF-I having
      lower basal serum and in-vitro GH levels than tumours unaffected by IGF-I (P <
      0.05). There was no effect on alpha-subunit secretion in any of the three tumours
      studied. PRL cosecretion was increased in 3/5 somatotrophinomas compared to
      control (20, 30 and 37%, P < 0.05), with tumours responding to IGF-I being
      associated with lower basal serum and in-vitro PRL levels than those tumours
      unaffected by IGF-I. IGF-I also increased PRL secretion in 2/2 prolactinomas (27
      and 32%, P < 0.05) compared with control. GH was inhibited and PRL secretion was
      stimulated by 1 and 10 nM IGF-I in the two dose-response studies. The
      proliferative labelling index did not exceed 1.9% in any tumour and no
      proliferative effect was found with 100 nM IGF-I in any somatotrophinoma.
      CONCLUSION: IGF-I inhibited tumorous GH in 62% and stimulated PRL secretion in
      71% of tumours over 4 days, without affecting alpha-subunit secretion or being
      mitogenic for somatotrophinoma cells in vitro. No hormonal effects were observed
      over short (4-hour) incubations. IGF-I may be a newly recognized factor directly
      stimulating tumorous PRL secretion.

PMID- 7525127
TI  - Treatment of linear localized scleroderma with the anti-allergic drug, tranilast.
AB  - A 14-year-old boy with linear localized scleroderma had a dramatic improvement in
      contractures after treatment with N-(3',4'-dimethoxycinnamoyl) anthranilic acid
      (tranilast, Rizaben). The observation that this anti-allergic drug was effective
      in localized scleroderma lends further support to the concept that mast cells
      play a role in increased collagen synthesis in this disease.

PMID- 7525129
TI  - Influence of an established acute phase response on the severity of experimental
      nephritis.
AB  - Small doses of lipopolysaccharide (LPS) induced an acute phase response (APR),
      and a number of studies have also shown that this greatly enhances the severity
      of glomerular injury in the heterologous phase of nephrotoxic nephritis (hNTN),
      an experimental model of anti-glomerular basement membrane (GBM) disease. Here,
      we examined the influence of pre-existing subclinical infection and raised APR,
      assessed by plasma alpha 2-macroglobulin (alpha 2-M) concentration, on the degree
      of injury in this model of nephritis. Studies were initially performed to
      determine the normal range of alpha 2-M in rats and its modulation by IL-6 and
      different doses of LPS. Plasma concentration of alpha 2-M was found to be
      variable and dependent on the weight of the rats. Single injections of either LPS
      or IL-6 had a comparable effect, and continuous perfusions of LPS caused a
      progressive increase in alpha 2-M which peaked at 48 h and declined gradually
      over 1 week. Following induction of nephritis with 10 mg of anti-GBM antibody,
      rats with raised alpha 2-M had 14 +/- 3 mg/24 h albuminuria compared with 4 +/- 1
      mg/24 h in rats with normal alpha 2-M (P < 0.001, Wilcoxon). Injection of 20 mg
      anti-GBM antibody caused 36 +/- 11 mg/24 h albuminuria compared with 16 +/- 4
      mg/24 h (P < 0.001), respectively. However, all these rats remained active and
      none of them died. In contrast, injection of 0.25 microgram LPS before induction
      of nephritis with 10 mg anti-GBM antibody, in rats with raised alpha 2-M, caused
      severe albuminuria (115 +/- 23 mg/24 h) compared with rats having normal levels
      of alpha 2-M (72 +/- 15 mg/24 h, P < 0.05). Furthermore, rats with raised alpha 2
      M also had severe systemic manifestations characterized by pulmonary haemorrhage
      and extensive glomerular thrombosis, and many of them died. These results
      demonstrate the potential effect of pre-existing subclinical infection and raised
      APR on severity of glomerular injury which may affect the outcome of experimental
      studies.

PMID- 7525130
TI  - Role of calcium-activated potassium channels in the relaxation of tracheal smooth
      muscles by forskolin.
AB  - 1. The role of calcium-activated potassium (KCa) channels in bronchodilation
      produced by a direct adenylyl cyclase activator, forskolin, was investigated. The
      involvement of intracellular cyclic AMP (cAMP) in the process was also examined.
      2. The isometric tension records from guinea-pig tracheal smooth muscles
      indicated that application of charybdotoxin (ChTX), a selective inhibitor of
      large conductance KCa channels, led to a suppression of the relaxant effect of
      forskolin in the precontracted tissue by carbachol (CCh). However, the inhibitory
      action by ChTX had a much greater effect on the relaxation caused by
      isoproterenol than by forskolin. 3. In contrast to the effect of ChTX,
      glybenclamide, a cromakalim-sensitive K+ channel inhibitor and apamin, a small
      conductance KCa channel blocker, had no effects on the bronchodilation produced
      by forskolin. 4. The effects of forskolin and nifedipine on tone produced by high
      K+ was compared. Concentration-inhibition curves in guinea-pig trachealis
      precontracted by 20 mmol/L K+ solution were similar for forskolin and nifedipine.
      Conversely, relaxation by forskolin was significantly diminished when tissues
      were contracted with 40 mmol/L K+ solution, whereas nifedipine relaxations were
      unaffected. 5. A single channel record from a cell-attached patch in a porcine
      tracheal myocyte demonstrated that forskolin stimulates reversibly KCa channels
      without affecting the unitary amplitude. 6. The results are consistent with
      forskolin-induced relaxation occurring at least in part through the opening of
      ChTX-sensitive KCa channels, by means of a cAMP-dependent channel
      modulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525128
TI  - Soluble endothelium-associated adhesion molecules in patients with Graves'
      disease.
AB  - The targeting and recruitment of inflammatory cells to vascular endothelium in
      Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1),
      endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion
      molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1),
      soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n =
      21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels
      of sICAM-1 were markedly elevated in patients with GD before treatment with
      thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition,
      elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml,
      respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were
      observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and
      sVCAM-1 dropped significantly after initiation of therapy and were within the
      normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM
      1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM
      1 correlated with the serum concentrations of anti-thyroid-stimulating hormone
      (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810,
      respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673
      and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab,
      TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found.
      In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM
      1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease
      activity.

PMID- 7525132
TI  - Rheumatoid arthritis and juvenile chronic arthritis: the role of the neuro
      endocrine system.
AB  - Various factors determine the outcome of rheumatoid arthritis and juvenile
      chronic arthritis. One of these factors is the neuro-endocrine system. In
      rheumatoid arthritis as well as in juvenile chronic arthritis, alterations of the
      autonomous nervous system do occur. In polyarticular and systemic juvenile
      chronic arthritis, during active disease the sensitivity for catecholamines
      changes. Under these conditions catecholamines cannot inhibit the immune
      response, which may have negative consequences for the course of the disease. In
      certain autoimmune animal models defects in the hypothalamus-pituitary-adrenal
      axis play a role in the pathogenesis of the disease. Studies in rheumatoid
      arthritis suggest a subtle insufficiency of the hypothalamus-pituitary-adrenal
      axis in rheumatoid arthritis. Proinflammatory substances such as Substance P, as
      well as (locally produced) opioids may contribute to disease activity.

PMID- 7525133
TI  - Melioidosis. Another etiology of granulomatous osteomyelitis. Report of 2 cases.
AB  - Two cases of granulomatous osteomyelitis caused by melioidosis are reported.
      Histologically, the granulomatous lesions were indistinguishable from
      tuberculosis and required confirmation with microbiological culture. It is
      important that melioidosis be considered in the differential diagnosis of
      granulomatous osteomyelitis since the treatment is quite different from
      tuberculosis.

PMID- 7525131
TI  - Involvement of nitric oxide in coronary vascular responses to 5-hydroxytryptamine
      in the anaesthetized greyhound.
AB  - 1. The effect of the intracoronary (i.c.) injection of 5-hydroxytryptamine (5-HT;
      0.1-1.0 micrograms/kg) was examined before and after inhibition of nitric oxide
      (NO) synthesis with N-nitro-L-arginine (NOLA; 5 mg/kg i.c.) in nine anaesthetized
      greyhounds. Before administration of NOLA, 5-HT increased coronary blood flow
      (CBF) but decreased large coronary artery diameter indicating simultaneous
      dilatation of resistance vessels and constriction of large arteries. 2. The
      administration of NOLA significantly decreased large coronary artery diameter and
      increased systemic arterial pressure. There was no significant effect on coronary
      vascular resistance or heart rate. In the presence of NOLA, the 5-HT-induced
      constriction of the large coronary artery was enhanced and the dilatation of the
      resistance vessels was reduced. In addition there was a secondary reduction in
      CBF, a response that was not observed before NOLA treatment. 3. The response to
      NOLA suggests that a basal release of NO is important in the regulation of
      coronary and systemic vascular tone. Nitric oxide is an important mediator of
      coronary vasodilator responses to 5-HT, and in addition the release of NO
      modulates 5HT-induced constriction of large coronary arteries.

PMID- 7525134
TI  - [A family of hereditary motor and sensory neuropathy type I with a new type of
      myelin P0 mutation].
AB  - A 26-year-old man had complaints of insidiously progressive muscle weakness of
      the legs, worse in the right leg than in the left. Slight to moderate degrees of
      asymmetrical muscular atrophy and weakness of the distal lower limb muscles,
      greater in the right leg than in the left, without fasciculation, were also
      observed. Pes equinovarus deformity of both feet was obvious. Muscle stretch
      reflexes were decreased in the upper limbs and absent in the lower limbs, without
      pathologic reflexes. Vibratory sensation was moderately decreased in the toes.
      The right median and tibial motor nerve conduction velocities were 19.4 and 10.5
      m/sec, respectively, with a markedly prolonged distal latency. No nerve action
      potentials were elicited from stimulation of the right and left sural nerves. A
      fascicular biopsy of the right sural nerve was performed. The myelinated fibers
      showing segmental de- and remyelination were frequently found in teased fiber
      preparations. Both demyelinated and remyelinated axons and onion-bulbs were
      frequently observed by light and electron microscopy in the Epon-embedded
      sections. Based on the neurological examinations and nerve conduction studies of
      the family members, an elder brother, father and grandmother of the proband were
      found to be affected by polyneuropathy. However, the mother, an uncle, an aunt,
      and a cousin of the proband were normal. Therefore, we concluded that this family
      had HMSN type I with autosomal dominant inheritance.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7525137
TI  - The CAT/CLAMS assessment for early intervention services. Clinical Adaptive
      Test/Clinical Linguistic and Auditory Milestone Scale.
AB  - The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale
      (CAT/CLAMS) is a relatively new test of language, problem-solving abilities, and
      visual-motor skills for children ages 0 to 36 months of age. This instrument was
      compared to the Bayley Mental Developmental Index (MDI), the generally accepted
      standard of infant developmental tests. This study evaluates 328 normal children
      tested in infancy and then at 18 and 30 months of age. Specificity was excellent
      (95% to 100%) at both 18- and 30-month levels when compared to the Bayley MDI.
      Sensitivity, however, was 21% at the 18-month level and 67% at the 30-month
      level. Predictive validity (.65) and within-test validity (.69) are good. The
      CAT/CLAMS compares favorably with the Bayley MDI assessment of children between
      18 and 30 months of age and can be used for clinical assessment of toddlers
      referred for development assessment prior to admission to early intervention
      programs.

PMID- 7525135
TI  - [Toxicity of AMPA, an excitatory amino acid, to rat spinal cord neurons under
      intrathecal administration].
AB  - The neurotoxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA), an agonist for glutamate receptors, was investigated by infusing
      adult rats with this agent intrathecally for either a short term (2 hours) or a
      long term (7 days) using a mechanical pump or a mini-osmotic pump, respectively.
      In the short-term infusion group, spasticity of the hindlimbs developed during
      infusion at 0.5 nmol/h or more of AMPA, tremors at 50 nmol/h or more, and
      flaccidity at 65 nmol/h or more. One day later, flaccid paralysis of the
      hindlimbs and urinary incontinence were observed in the rats that received 50
      nmol/h (total dose: 100 nmol) or more of AMPA. These symptoms were thought to be
      permanent. On the other hand, in the long-term infusion group, behavioral changes
      were apparent only after second postoperative day, when rats displayed hindlimb
      palsy or urinary incontinence. Behavioral deficits became progressively severe,
      and rats usually displayed both hindlimb paraplegia and urinary incontinence by
      the 7th postoperative day. These progressive behavioral deficits were induced in
      a dose-dependent manner in rats that received AMPA at doses greater than 0.1
      nmol/h. Gliosis with neuronal loss involving the partial (lumbar segments) and
      whole (sacral segments) gray matter of the spinal cord was induced in rats that
      received AMPA at doses greater than 50 nmol/h in the short-term infusion group
      and greater than 0.1 nmol/h in the long-term infusion group.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7525136
TI  - Early outcome determination of low-birth-weight infants using the
      Neurodevelopmental Risk Examination.
AB  - A neonatal neurodevelopmental assessment, the Neurodevelopmental Risk Examination
      (NRE), was developed, through adaptation of the scoring of the Allen/Capute
      neonatal neurodevelopmental examination, for screening the development of low
      birth-weight (LBW) infants in the newborn period. A pilot study was conducted of
      the NRE and its ability to predict motor and cognitive outcome in LBW infants.
      The NRE was performed on 92 LBW infants (mean birth weight 1,192 g; mean
      gestational age 29 weeks) at or near term and included assessments of
      sensory/behavioral response, axial tone, extremity tone, deep tendon reflexes,
      and primitive reflexes. Developmental outcome was assessed at a mean age of 13.7
      months by neuromotor examination and by the mental scale of the Bayley Scales of
      Infant Development. The NRE total risk score, reflecting overall
      neurodevelopmental status, correlated well with motor and cognitive outcomes (r =
      .50, P = .0001; and r = -.38, P = .0001, respectively). When infants were
      clustered into risk groups based upon NRE score (69 infants were deemed low-risk,
      20 moderate-risk, and three high-risk), a strong relationship to outcome was
      maintained (motor outcome: chi 2 = 43.6, P < .0001; cognitive outcome: analysis
      of variance (ANOVA) F = 6.78, df(2.89), P = .002). All subcategories of the
      examination, except primitive reflexes, were associated with outcome. Therefore,
      by using a simple method of scoring and interpretation, the NRE can validly
      predict motor and cognitive outcome in LBW infants.

PMID- 7525138
TI  - CAT/CLAMS. A tool for the pediatric evaluation of infants and young children with
      developmental delay. Clinical Adaptive Test/Clinical Linguistic and Auditory
      Milestone Scale.
AB  - The American Academy of Pediatrics recommends regular developmental screening as
      a part of routine child health supervision. However, the pediatrician has a
      limited number of tools available to further evaluate a child who is found to be
      suspect or abnormal on a developmental screening test. The Clinical Adaptive
      Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was therefore
      developed to provide pediatricians with a technique to assess infants and
      toddlers with suspected developmental delay. The CAT/CLAMS demonstrated strong
      psychometric properties. Concurrent validity with the Bayley Scales of Infant
      Development (BSID) was demonstrated in 43 children ages 12 to 19 months who were
      tested on three occasions with both instruments (correlation coefficient ranging
      between 0.63 and 0.87; P < .001). Predictive validity 6 and 12 months later was
      also demonstrated in this population with correlation coefficients ranging
      between 0.73 and 0.77, significant at the P = .001 level. Utilizing the CAT/CLAMS
      as part of the pediatrician's evaluation of children with developmental concerns
      would allow the pediatrician to compare language and nonlanguage problem-solving
      abilities and, therefore, aid in diagnosis and appropriate referral.

PMID- 7525141
TI  - Embolization in the palliation of complications of inoperable primary pancreatic
      neoplasms.
AB  - Primary pancreatic neoplasm typically presents at an advanced stage where
      surgical management may not be feasible. These patients are often symptomatic due
      to biliary obstruction but problems may also include gastrointestinal bleeding
      and endocrinological complications. We describe two cases illustrating the use of
      palliative embolization in the control of biochemical and haemorrhagic
      complications of primary pancreatic neoplasm. In one case, massive
      gastrointestinal bleeding from an inoperable primary pancreatic carcinoma was
      controlled by two embolization procedures to produce devascularization of the
      primary lesion. In a second case, life-threatening hypercalcaemia was thought to
      be due to secretion of a parathormone-like material from an inoperable islet cell
      tumour. There was no evidence of liver metastases and the pancreatic mass was
      embolized, following which serum calcium was reduced to near normal levels with
      considerable clinical improvement. We conclude that there is a role for
      embolization of inoperable primary pancreatic neoplasm in the palliation of
      biochemical or haemorrhagic complications of these tumours.

PMID- 7525139
TI  - Neurodevelopment in pediatric HIV infection. The use of CAT/CLAMS. Clinical
      Adaptive Test/Clinical Linguistic and Auditory Milestone Scale.
AB  - Pediatric neuro-AIDS may be the first clinical manifestation of HIV infection in
      children born to HIV-infected mothers. As part of the neurodevelopmental
      examination of children, the Clinical Adaptive Test/Clinical Linguistic and
      Auditory Milestone Scale (CAT/CLAMS) was investigated as a tool for pediatricians
      to use to monitor the development of children at risk for HIV infection. The
      CAT/CLAMS was found to detect neurodevelopmental differences between HIV-infected
      and uninfected children at 12 and 18 months of age. Good correlations were found
      between the CAT/CLAMS and concurrently administered Bayley Scales of Infant
      Development. These findings suggest that the CAT/CLAMS should be considered as a
      part of the neurodevelopmental examination of children at risk for pediatric
      neuro-AIDS.

PMID- 7525140
TI  - The Functional Independence Measure for Children (WeeFIM). Conceptual basis and
      pilot use in children with developmental disabilities.
AB  - Few tools are available to pediatricians for tracking and monitoring disability
      status in children. We describe the conceptual basis and pilot use of the
      Functional Independence Measure for Children (WeeFIM). Our pilot use of this
      instrument in children with limb deficiency, Down's syndrome, spina bifida,
      cerebral palsy, and extreme prematurity demonstrates that the WeeFIM is a valid
      measure for tracking disability in preschool age and middle childhood. The WeeFIM
      measures the impact of developmental strengths and difficulties on independence
      at home, in school, and in the community. This allows the pediatrician to
      prioritize interventions for enhancing comprehensive functional outcomes and
      supporting families.

PMID- 7525142
TI  - Effect of the serine protease inhibitor, aprotinin, on systemic haemodynamics and
      renal function in patients with hepatic cirrhosis and ascites.
AB  - 1. Previous studies have documented activation of protease enzymes, such as the
      plasma kallikrein-kinin system, in hepatic cirrhosis. Increased plasma kinin
      generation could contribute to pathological systemic vasodilatation in cirrhosis,
      and reduced systemic vascular resistance has been suggested as a trigger to renal
      sodium retention in this disease. We investigated the effect of aprotinin, a
      protease inhibitor which binds to plasma kallikrein, on systemic haemodynamics
      and renal function in patients with hepatic cirrhosis and ascites. 2. Aprotinin
      was infused intravenously in high dosage (2 x 10(6) kallikrein inhibitory units
      loading, 1 x 10(6) kallikrein inhibitory units/h). 3. Of 13 patients, 10 had a
      low systemic vascular resistance (< 1200 dyn s cm-5) at baseline. In this group,
      eight showed an increase in systemic vascular resistance during aprotinin
      infusion. Overall, the increase in systemic vascular resistance was significant,
      and there was a small but significant increase in mean arterial pressure. In all
      patients, there were increases in renal plasma flow, glomerular filtration rate,
      and absolute and fractional urinary sodium excretion during aprotinin infusion.
      4. Plasma renin activity, plasma angiotensin II and plasma aldosterone fell
      significantly during aprotinin infusion. Plasma prekallikrein, plasma
      noradrenaline and plasma atrial natriuretic peptide did not change. Plasma
      aprotinin concentration was 209 +/- 11 kallikrein inhibitory units/ml at the end
      of the infusion. 5. Before and during the infusion, there was a significant
      negative correlation between systematic vascular resistance and plasma renin
      activity. There was a positive correlation between the change in systemic
      vascular resistance and the change in renal plasma flow during aprotinin
      infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525143
TI  - [HCV infection and risk of transfusion in the area of Tivoli and its
      surroundings].
AB  - The positivity of the anti-HCV antibody has been studied by means of an immuno
      enzymatic solid phase method, on 1.605 blood samples. They were drawn from 5
      groups of people, during the period from February 1 to October 31, 1992: a) all
      blood donors who made the donation at the Transfusion Service of Tivoli Hospital
      during that period; b) all intravenous drug users who came to Tivoli Hospital for
      control; c) all patients in the Contagious Disease Section with suspected liver
      disease, always during the same period; d) all patients with suspected liver
      disease from other Sections of our Hospital; e) all out-patients who came to our
      Service during the same period to have their hepatitis markers studied. The
      highest prevalence of HCV Ab positivity was in the drug users, with a prevalence
      of 80.9%; far from this value, the next two groups were the patients from the
      Contagious Disease Section (positivity: 23.4%), and from the other hospital
      Sections (positivity: 20.1%). In the out-patient group only 9.7% were positive
      and among blood donors only 0.35%. In all 5 groups the HCV-positive subjects were
      in many cases positive for B hepatitis too; and very often they presented high
      levels of ALT. These results confirm that in some the percentage of positive
      subjects for C hepatitis or for B & hepatitis; very high; therefore the authors
      underline the great importance to exclude all members of these groups from the
      donation of blood, its components, and organs too, even if the tests are
      negative.

PMID- 7525145
TI  - Human and mouse T-cell-receptor loci: the importance of comparative large-scale
      DNA sequence analyses.
AB  - It is our belief that large-scale DNA sequencing will revolutionize the study of
      molecular biology, developmental biology, genetics, and evolution for the TCR
      gene families and, indeed, all multigene families. We also stress the power of
      comparative analyses for large-scale DNA sequencing efforts.

PMID- 7525146
TI  - Two DNA polymerases: HIV reverse transcriptase and the Klenow fragment of
      Escherichia coli DNA polymerase I.

PMID- 7525147
TI  - Telomerase and telomere-length regulation: lessons from small eukaryotes to
      mammals.

PMID- 7525144
TI  - Hydration of biological macromolecules in solution: surface structure and
      molecular recognition.

PMID- 7525148
TI  - From the chromosomal loops and the scaffold to the classic bands of metaphase
      chromosomes.

PMID- 7525149
TI  - Role of chromosome territories in the functional compartmentalization of the cell
      nucleus.

PMID- 7525152
TI  - Precocious cessation of intestinal macromolecular transport and digestive enzymes
      development by prostaglandin E2 in suckling rats.
AB  - The effect of repeated oral administration of prostaglandin analogue (dmPGE2) on
      intestinal macromolecular transport and digestive enzymes development were
      investigated in the suckling rats. By the administration of dmPGE2 for 7 days,
      precocious induction of maltase activity, depression of amylase activity and
      enhancement of trypsin activity in the pancreas occurred. Absorption of bovine
      IgG was dose dependently depressed by dmPGE2 treatments. The intestinal cessation
      was also observed in the adrenalectomized pups, but was not influenced by
      difluoromethyl ornithine administration. These results suggest that oral
      administration of PGE2 induces precocious maturation of the small intestine and
      exocrine pancreas and that the intestinal cessation is not directly related to
      ornithine decarboxylase activity in the suckling rats.

PMID- 7525150
TI  - Mechanisms of intracellular transcript localization and export in early
      Drosophila embryos.

PMID- 7525153
TI  - Porcine insulin-like growth factor (IGF)-binding protein-3 elicits bi-phasic
      effects on IGF-I stimulated DNA synthesis in neonatal porcine skin fibroblasts.
AB  - The present study was undertaken to investigate the effects of porcine IGFBP-3 on
      IGF-I stimulated DNA synthesis in neonatal porcine skin fibroblasts. IGF-I
      stimulated DNA synthesis in skin fibroblasts in a concentration dependent manner.
      DNA synthesis was maximally stimulated by 5 to 20 fold at 5 nM IGF-I; half
      maximal stimulation was observed at approximately 1 nM IGF-I. Co-incubation of
      IGFBP-3 with a maximally effective dose of IGF-I (10 nM) did not inhibit the
      stimulatory effects of IGF-I on DNA synthesis. In contrast, when IGFBP-3 at
      concentrations of 0 to 20 nM was co-incubated with 1 nM IGF-I, a bi-phasic dose
      response was observed with IGFBP-3 being inhibitory only at a 10 to 20 fold molar
      excess to IGF-I. Based on the approximately equal molar ratio of IGFBP-3:IGF-I
      present in the circulation of control and pST-treated pigs our results suggest
      that IGFBP-3 does not inhibit the mitogenic effects of IGF-I. In summary, these
      results indicate that the combination of IGFBP-3 with IGF-I optimizes mitogenic
      signalling via the type I IGF receptor and suggest that IGFBP-3 does not inhibit
      the effects of ST that are mediated by IGF-I.

PMID- 7525151
TI  - Probing functional organization within the nucleus: is genome structure
      integrated with RNA metabolism?

PMID- 7525154
TI  - Hepatitis C treatment.

PMID- 7525155
TI  - Impacts of blood screening on the incidence of posttransfusion hepatitis C in
      Japan.

PMID- 7525156
TI  - Development of screening and confirmation tests for antibodies to hepatitis C
      virus.

PMID- 7525158
TI  - Hepatitis C virus and hepatocellular carcinoma.

PMID- 7525157
TI  - Autoimmune hepatitis and hepatitis C virus infection.

PMID- 7525159
TI  - A spot test for protein detection and semiquantitative estimation in small
      samples.
AB  - Modern biological experiments, conducted on mini- and micro-scales require
      methods for protein detection in small samples. The method proposed here is based
      on visual inspection of protein dots immobilized on nitrocellulose filters and
      stained with the common protein dye amido black. It allows detection and
      semiquantitative determination of protein concentrations in a wide range.

PMID- 7525160
TI  - Staining of human telomeres with primed in situ labeling (PRINS).
AB  - As described, the PRINS method is a very rapid and reliable way of staining human
      telomeres. To obtain the maximum frequency of stained telomeres, the primer
      (CCCTAA)7 should be used, although the average frequency never quite reaches
      100%. The frequency is strongly dependent on the age of the individual, being
      significantly higher in children and newborns than in adults. A difference
      between the (CCCTAA)7 primer and the complementary primer is demonstrated and a
      possible explanation is proposed, namely, that gaps in the C-rich strand cause
      chain elongation termination after the addition of only one dTTP molecule.

PMID- 7525161
TI  - Human AQP2 and MIP genes, two members of the MIP family, map within chromosome
      band 12q13 on the basis of two-color FISH.
AB  - The human AQP2 (collecting duct water channel, aquaporin 2) gene encodes a 271
      amino acid protein and is a member of the MIP (major intrinsic protein of lens
      fiber) gene family. Using two-color fluorescence in situ hybridization on high
      resolution R-banded chromosomes and human genomic DNA clones for AQP2 and MIP as
      probes, we found that both genes mapped closely within the human chromosome
      region 12q13.

PMID- 7525164
TI  - Production and characterization of CC-1 second generation monoclonal antibodies
      by intrasplenic deposited immunization with minute amounts of antigen.

PMID- 7525163
TI  - Primary pulmonary germ cell tumor with blastomatous differentiation.
AB  - We describe the clinical and pathologic findings of a patient with mixed blastoma
      germ cell malignancy primary in the lung. Serum alpha-fetoprotein levels were
      elevated at presentation, and normalized with anti-germ cell chemotherapy. The
      resection specimen contained massively necrotic germ cell tumor with viable
      mature neural tissue, plus viable biphasic blastoma with stromal bone and
      skeletal muscle differentiation. It is not clear whether the germ cell component
      represents unusual differentiation of a somatic cell line or whether the blastoma
      component represents an unusual pattern of teratomatous differentiation.

PMID- 7525162
TI  - The impact of aprotinin on coronary artery bypass graft patency.
AB  - STUDY DESIGN: Aprotinin has recently been shown to reduce postoperative bleeding
      and transfusion requirements associated with coronary artery bypass grafting. One
      concern with its use, however, is that it may have a deleterious effect on graft
      patency because it promotes hemostasis. Forty-seven patients undergoing coronary
      artery bypass. Forty-seven patients undergoing coronary artery bypass grafting
      were enrolled in a prospective, randomized double-blind trial of aprotinin to
      determine the effect of this agent on postoperative bleeding, transfusion
      requirements, renal function, and graft patency. The study group was comprised of
      the 32 patients who underwent technically adequate ultrafast CT scans 6 to 8
      weeks postoperatively to determine graft patency. Sixteen patients received
      aprotinin (aprotinin group) and 16 received placebo (control group). RESULTS:
      Demographic and operative descriptors were comparable between groups.
      Postoperative mediastinal and chest tube drainage in the aprotinin group was
      significantly less than that in the control group (722 vs 1,540 mL; p = 0.0006)
      and the mean blood transfusion requirements were less, but this did not reach
      significance (125 vs 297 mL; p = 0.42). Analysis of graft patency by patients
      revealed that 5 patients in the aprotinin group (31%) had at least one occluded
      graft, while none of the patients in the control group had an occluded graft (p =
      0.04). Analysis by graft revealed that 38 of 43 grafts placed in the aprotinin
      group were patent, while all 38 grafts placed in the placebo group were patent
      (88.4 vs 100%; p = 0.057). There was no difference in the incidence of myocardial
      infarction, renal dysfunction or hematologic indexes at discharge between the
      groups, or evidence of other thrombotic complications. CONCLUSION: We conclude
      that high-dose aprotinin is effective in reducing hemorrhage after coronary
      artery bypass grafting. However, its routine use should be approached cautiously
      due to its possible adverse effects on graft patency.

PMID- 7525166
TI  - [The diagnostic value of anti-HCV test in HCV infection].
AB  - Two hundred and ninety-six samples of patient serum and 28 samples of donor serum
      were tested for anti-HCV with second generation domestic made testing kit, and
      for HCV RNA with PCR assay. The aim of this study is to assess the diagnostic
      value of anti-HCV test in HCV infection and to discuss its value in screening of
      donors. The results were as follows HCV RNA was detected in 81.6% of the anti-HCV
      positive patient samples and in 21.7% of the anti-HCV negative patient samples.
      HCV RNA was not detected in 28 anti-HCV negative donors. These results reveals
      that positive anti-HCV is of high diagnostic value in HCV infection. Anti-HCV
      negative could not exclude HCV infection for samples suspected of HCV infection.
      However, screening donors with anti-HCV probably decreases HCV RNA positive rate
      considerably.

PMID- 7525165
TI  - [Pain assessment and therapy in bronchial carcinoma].
AB  - In the period from 1983-1991 133 patients (102 men, 31 women) with lung cancer
      were treated in our pain clinic for 8083 days. Pain was associated with tumour
      infiltration in 86% of patients and related to therapy in 15%. Even in 6 of 8
      patients who were admitted with a diagnosis of "postthoracotomy syndrome" and in
      all 4 patients with "postradiation syndrome" local recurrence was diagnosed
      during follow-up. All 17 cases of brachial plexus lesions were caused by local
      tumour spread. Symptomatic treatment according to WHO guidelines resulted in good
      pain relief in 92% of patients and on 82% of days. The incidence of dyspnea
      decreased from 51% of the patients to 16%. Strong opioids were used on 56% of
      treatment days. Parenteral or spinal administration of opioids was necessary on
      3% of days only.

PMID- 7525167
TI  - Effect of buprenorphine on pancreatic enzyme synthesis and secretion in normal
      rats and rats with acute edematous pancreatitis.
AB  - Pancreatic enzyme secretion is inhibited during acute pancreatitis, resulting in
      an increase in acinar zymogen content. Since the premature activation of zymogens
      has been assigned a central role in the pathogenesis of acute pancreatitis,
      minimizing the amount of stored zymogens might lead to less severe acute
      pancreatitis. Inhibition of enzyme synthesis or stimulation of enzyme secretion
      would result in reduction of zymogen stores. Opiates have a varying effect on
      pancreatic secretion, depending on the dosage, site of administration, and
      presence of pancreatic stimulants. The effect of opiates and acute pancreatitis
      on individual pancreatic enzyme synthesis is unknown. The following study was
      undertaken in order to examine the effects of an opiate on pancreatic enzyme
      secretion and synthesis during experimental acute pancreatitis. Four groups of
      rats were studied. Group I received cerulein (25 micrograms/kg); group II
      received an opiate, buprenorphine (BPN, 0.5 mg/kg); and group III received
      cerulein and BPN. Drugs were dissolved in gelatin/saline and injected
      subcutaneously. A control group (group IV) received only gelatin/saline. Rats
      were sacrificed 4 hr after injection, and pancreatic mass was measured.
      Pancreatic acini were prepared and assayed for amylase and DNA content. Amylase,
      trypsinogen, chymotrypsinogen and lipase synthesis, and amylase secretion were
      measured for 2 hr. Results showed that, compared to controls, acini of rats with
      AP had increased amylase content, a finding consistent with decreased in vivo
      amylase secretion. Total protein and individual enzyme synthesis rates were
      significantly lower in the acini of the rats with AP than in those of the
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525168
TI  - Alpha-2-macroglobulin and hepatic fibrosis. Diagnostic interest.
AB  - Alpha-2-macroglobulin (A2M) is a proteinase inhibitor. Cells synthesizing A2M are
      in first-order hepatocytes and in second-order activated Ito cells (in culture
      starting at day 4-5 after seeding). This study was undertaken in 525 alcoholic
      patients with different histological stages of alcoholic liver disease to assess
      if the A2M could improve the diagnostic value of PGA index for detection of
      cirrhosis or fibrosis among drinkers, particularly in patients without clinical
      symptoms of liver failure and portal hypertension, and to assess the specific
      correlation of serum A2M with the score of liver fibrosis adjusted for steatosis
      and alcoholic hepatitis and thereafter adjusted for GGT, PT, and ApoA1, the three
      components of the PGA index. In 525 alcoholic patients, we have demonstrated the
      independent diagnostic value of A2M. The predictive values of the weighted score,
      using linear discriminant function combining PT, GGT, ApoA1 and A2M of the PGAA
      score and of the PGA score were assessed in a training step and validated in a
      second step. Then, 316 alcoholic clinically asymptomatic patients were studied.
      In these patients, the discriminant function permitted correct classification of
      72% of patients. The PGAA index had comparable diagnostic value with 70% of
      patients correctly classified. On the other hand, the PGA index including only
      PT, GGT, and ApoA1 had classified correctly less patients (65%) than the
      discriminant function and the PGAA index (P < 0.01). For a value of 7, PGAA had
      79% specificity and 89% sensitivity for the diagnosis of cirrhosis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7525171
TI  - More than you ever wanted to know (but need to know) about glycohemoglobin
      testing.

PMID- 7525170
TI  - Fetal hemoglobin in diabetic patients.
AB  - OBJECTIVE: To determine the occurrence of elevated fetal hemoglobin (HbF) among
      the diabetic population and determine the clinical situation of importance.
      RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted. HbA1c and HbF
      were measured with high-performance liquid chromatography in 1,104 consecutive
      diabetic patients attending our clinic for HbA1c determination. The expression of
      clinical correlations between the high and low HbF group was performed for adults
      (> or = 15 years). A nondiabetic control group (n = 258) with the same age and
      sex distribution was included. RESULTS: HbF was elevated (> 1.0% of total
      hemoglobin) in 7.5% of the total diabetic group. In the adult diabetic group, HbF
      was elevated in 6.5% of the patients, and in the control group, HbF was elevated
      in 1.9% (P < 0.01). In the insulin-treated adult group, HbF was elevated in 10.2%
      of the patients, and in the non-insulin-treated group, HbF was elevated in 3.8%.
      The mean HbA1c was 8.90 +/- 2.00% among the patients and 5.52 +/- 0.53% in the
      control subjects (P < 0.001). Patients with elevated HbF were younger (P < 0.02)
      and more often on insulin therapy (P < 0.001) or type I diabetic patients (P <
      0.001). Sex, glycemic control, or duration of diabetes were not significantly
      different in the patients with high or low HbF. Correlation was not detected
      between the amount of HbF and HbA1c or age in the group of patients with elevated
      HbF. Hemoglobinopathies, anemias, or malignancies were not diagnosed from the
      patients with high HbF. CONCLUSIONS: Level of HbF is increased (> 1.0%) among
      7.5% of unselected diabetic patients. In adult (> or = 15 years) diabetic
      patients, it is increased among 6.5%, which is 3.4 times more often than in the
      control population. Acute hematological conditions or malignancies do not explain
      the difference. Elevated HbF seems to be associated with type I diabetes and
      insulin treatment.

PMID- 7525169
TI  - Relationship between serum HCV markers and response to interferon therapy in
      chronic hepatitis C. Evaluation of HCV genotypes during and after long-term
      follow-up.
AB  - Hepatitis C virus is the most frequent cause of chronic non-A, non-B hepatitis,
      and the antibodies to structural and nonstructural proteins encoded by viral
      genome have been suggested to be markers of ongoing HCV infection. We studied the
      behavior of these antibodies during interferon therapy in 18 patients with
      chronic hepatitis C and also during a follow-up period of at least four years. A
      significant decrease of anti-HCV titer was found only in patients who had shown
      positive response to therapy and all of them were anti-HCV negative at the end of
      follow-up. Analysis by recombinant immunoblotting assay showed that only anti
      c100 were affected by interferon therapy, whereas anti-c22 and anti-c33 were not
      modified. Using polymerase chain reaction to detect small amounts of HCV genome
      in serum, we could confirm that the behavior of HCV-RNA during and after
      interferon therapy is similar to that of anti-HCV and the loss of anti-c100 seems
      to be closely related to HCV-RNA disappearance from serum. Our patients with
      chronic hepatitis C were found to be of type 1b and 2, according to the recent
      score of Simmonds, and the clearance of serum HCV-RNA during treatment and its
      sustained negative status are closely related to genotype 2 and to long-term
      positive response to interferon.

PMID- 7525175
TI  - [Treatment of clozapine-induced agranulocytosis using granulocyte colony
      stimulating factor].
AB  - A 20-year-old woman had for the preceding 11 weeks been receiving clozapine (225
      mg/d) for an endogenous psychosis when she developed a urinary tract infection
      with fever. The blood count showed 2100 white cells/microliter without any
      neutrophils, the count having been normal 5 days previously. Physical examination
      was normal except for a fever of 39 degrees C and parodontitis. The red cell
      count was 3.9 mill/microliters, platelet count 443,000/microliters. Bone marrow
      biopsy revealed almost complete stop of proliferation and maturation in
      granulocytopoiesis so that granulocyte colony-stimulating factor (300 micrograms
      daily subcutaneously) had to be administered in addition to supportive measures.
      The granulocyte count at first fell to 1400 cells/microliter, but nine days after
      starting the drug myeloblasts, promyelocytes and myelocytes reappeared in
      peripheral blood for the first time. On the tenth day, administration of the
      growth factor was discontinued. An overshoot granulocytopoiesis occurred in bone
      marrow on the 13th day; on the 22nd day after treatment had been started the
      patient had a normal blood picture and was discharged.

PMID- 7525173
TI  - [Clinical study of recombinant human granulocyte colony stimulating factor (rhG
      CSF) on leukopenia induced by chemotherapy in cancer patients].
AB  - The clinical usefulness of Recombinant Human Granulocyte Colony Stimulating
      Factor (rhG-CSF, Filgrastim, GRAN) was evaluated in patients with leukopenia and
      neutropenia following chemotherapy for non-Hodgkin's lymphoma, lung cancer and
      breast cancer. During chemotherapy when patients' leukocyte count (WBC) fell
      below 4.0 x 10(9)/L.rhG-CSF(GRAN) at a dose of 75 micrograms/body.day was given
      subcutaneously 48 hours after the termination of chemotherapy. The results
      indicated that rhG-CSF(GRAN) could elevate nadirs of WBC and significantly
      shortened leukopenic period with WBC below 4.0 x 10(9)/L and expedited the
      recovery of WBC. rhG-CSF (GRAN)'s side effects were mild.

PMID- 7525174
TI  - [Primary hepatic carcinoma treated by chemoembolization--a clinical analysis of
      20 cases with survival period longer than 3 years].
AB  - Advanced primary hepatic carcinoma was treated in 110 patients by percutaneous
      transhepatic arterial chemoembolization (TAE) from January 1987 to October 1989
      according to Seldinger's protocol with mitomycin C, Adriamycin or carboplatin and
      40% iodized oil. The treatment was given once every 4-12 weeks and the number of
      treatment for each patient varied from 2 to 19 depending on patients' condition
      and response. Of the 110 patients, 20 survived > 3 years, among which 7 survived
      > 4 years and 4 survived > 5 years. Following treatment, a greater than 50%
      reduction of tumor size was observed in 13 cases and a decrease in AFP to normal
      level in 12 cases. Seven patients were treated with TAE followed by tumor
      resection and, 2 patients were treated with TAE due to recurrence after tumor
      resection 11 patients were treated with TAE alone. The mean survival period was
      53.1 and 43.5 months, respectively. TAE is considered as the first choice of
      palliative treatment for patients with advanced hepatic carcinoma. Factors that
      might influence the result of TAE treatment are discussed.

PMID- 7525172
TI  - Glycosylated haemoglobin in the fetus: chemistry, laboratory measurements and
      future clinical implications.

PMID- 7525177
TI  - [The current value of laparoscopy in cancer surgery].

PMID- 7525176
TI  - [Tumor vascular invasion in breast carcinoma. Hematoxylin-eosin versus
      immunohistochemical staining for factor VIII antigen].
AB  - Blood vessel invasion was investigated with haematoxylin-eosin (HE) staining and
      immunohistochemical staining for factor VIII antigen (F VIII) in 106 patients
      with primary carcinoma of the breast, in order to compare their value in
      prognosticating the probability of recurrence. Blood vessel invasion was
      diagnosed in 65 cases (61.9%) by HE, but in only 45 (43.4%) by F VIII staining.
      Lymph-node status and blood vessel invasion correlated positively on HE (r =
      0.73; P = 0.0001), but not so on F VIII staining. Multivariate logistic
      regression showed blood vessel invasion to be a strongly independent prognostic
      factor for recurrence-free survival with F VIII staining (odds ratio: = 7.19; P =
      0.0001), while HE staining was not independent from other prognostic factors.
      These preliminary data thus suggest that demonstrating vascular invasion by F
      VIII staining may identify those patients with a very high risk of recurrence,
      independent of lymph-node status.

PMID- 7525178
TI  - Programming gene expression in developing epidermis.
AB  - As the major proteins of adult keratinocytes, keratins provide biochemical
      markers for exploring mouse epidermal embryogenesis. Here, we used a modified
      method of whole-mount in situ hybridization to track skin-specific expression of
      endogenous keratin mRNAs throughout embryogenesis. To monitor transcriptional
      regulation, we coupled this with beta-galactosidase expression of a human
      epidermal keratin promoter-driven transgene. These studies have radically changed
      our perception of how the program of gene expression becomes established during
      epidermal development. Specifically, we have discovered that (1) basal keratin
      (K5 and K14) genes are first detected at E9.5 in a highly regional fashion, and
      surprisingly as early as the single layered ectodermal stage; (2) the early
      patterns do not correlate with morphogenesis per se, but rather with regional
      variations in the embryonic origin of underlying mesenchyme, supporting
      morphogenetic criteria that early inductive cues are mesenchymal; (3) epidermal
      keratin genes are expressed in periderm, supporting the notion that this layer
      arises from ectodermal stratification, even though it is simple epithelial-like
      in morphology and is subsequently sloughed during development; (4) later
      embryonic patterns of K5 and K14 gene expression parallel proliferative capacity
      and not stratification; and (5) K1 and K10 mRNAs are first detected as early as
      E13.5, and their patterns correlate with differentiation and not stratification.
      These patterns of epidermal gene expression led us to explore whether potential
      transcriptional regulators of these genes are expressed similarly. We show that
      AP2 (but not Sp1) cRNAs hybridize in a pattern similar to, but preceding that of
      basal keratin cRNAs. Finally, using gene expression in cultured cells, we
      demonstrate that AP2 has a strong inductive effect on basal keratin expression in
      a cellular environment that does not normally possess AP2 activity.

PMID- 7525179
TI  - Specific roles of the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins
      in avian neural crest cell adhesion and migration on vitronectin.
AB  - To identify potentially important extracellular matrix adhesive molecules in
      neural crest cell migration, the possible role of vitronectin and its
      corresponding integrin receptors was examined in the adhesion and migration of
      avian neural crest cells in vitro. Adhesion and migration on vitronectin were
      comparable to those found on fibronectin and could be almost entirely abolished
      by antibodies against vitronectin and by RGD peptides. Immunoprecipitation and
      immunocytochemistry analyses revealed that neural crest cells expressed primarily
      the alpha V beta 1, alpha V beta 3 and alpha V beta 5 integrins as possible
      vitronectin receptors. Inhibition assays of cellular adhesion and migration with
      function-perturbing antibodies demonstrated that adhesion of neural crest cells
      to vitronectin was mediated essentially by one or more of the different alpha V
      integrins, with a possible preeminence of alpha V beta 1, whereas cell migration
      involved mostly the alpha V beta 3 and alpha V beta 5 integrins.
      Immunofluorescence labeling of cultured motile neural crest cells revealed that
      the alpha V integrins are differentially distributed on the cell surface. The
      beta 1 and alpha V subunits were both diffuse on the surface of cells and in
      focal adhesion sites in association with vinculin, talin and alpha-actinin,
      whereas the alpha V beta 3 and alpha V beta 5 integrins were essentially diffuse
      on the cell surface. Finally, vitronectin could be detected by immunoblotting and
      immunohistochemistry in the early embryo during the ontogeny of the neural crest.
      It was in particular closely associated with the surface of migrating neural
      crest cells. In conclusion, our study indicates that neural crest cells can
      adhere to and migrate on vitronectin in vitro by an RGD-dependent mechanism
      involving at least the alpha V beta 1, alpha V beta 3 and alpha V beta 5
      integrins and that these integrins may have specific roles in the control of cell
      adhesion and migration.

PMID- 7525180
TI  - A new strategy for the treatment of inflammatory pain. Prevention or elimination
      of central sensitization.
AB  - The optimal treatment of pain requires an understanding of the mechanisms
      involved. Pain is a sensory end-point that can be generated by a number of
      dissimilar processes. Consequently, the concept of treating pain as a unitary
      symptom is obsolete. The mechanisms responsible for specific types of pain need
      to be understood, and particular treatments should be aimed selectively at the
      various subtypes of pain. A major breakthrough in our understanding of pain has
      come from the appreciation that clinical pain is qualitatively quite different
      from physiological or nociceptive pain and is characterised by the appearance of
      abnormal hypersensitivity. Clinical pain is more than a reflection of sustained
      peripheral input and it is, to a large extent, the expression of changes produced
      in the CNS, including the phenomenon of central sensitization. We need to treat
      both the disease/injury process in the periphery and the changes it induces or
      triggers in the CNS. Prevention of central sensitization will substantially
      eliminate the hyperalgesia and allodynia that patients find so distressing, and
      it offers new possibilities for the development of novel analgesics or
      antihypersensitivity drugs.

PMID- 7525181
TI  - Spinal mediators of hyperalgesia.
AB  - Neuronal plasticity associated with altered sensations arising from tissue damage
      involves both established (e.g. substance P and excitatory amino acids) and novel
      (e.g. nitric oxide and metabolites of arachidonic acid) mediators released from
      terminals of primary afferent neurons or synthesised in the spinal cord. These
      and other mediators lead to activity-dependent synaptic plasticity and enhanced
      sensitivity to noxious stimuli (hyperalgesia). Activation of the N-methyl-D
      aspartate (NMDA) receptor results in a calcium-dependent production of nitric
      oxide, while activation of alpha-amino-3-hydroxy-5-methylisoxazole-5-propionate
      (AMPA)-and 1,3- trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD)
      sensitive glutamate receptors results in a phospholipase A2 (PLA2)-mediated
      production of different intracellular mediators, including arachidonic acid.
      Thermal hyperalgesia requires NMDA receptor activation and is primarily mediated
      by production of nitric oxide. Mechanical hyperalgesia requires AMPA and
      metabotropic glutamate receptor coactivation, and is primarily mediated by cyclo
      oxygenase products of arachidonic acid metabolism.

PMID- 7525182
TI  - Spinal cord effects of antipyretic analgesics.
AB  - Tissue damage results in the release of inflammatory mediators, including
      prostaglandins, which sensitive fine nerve endings in the periphery to mechanical
      and thermal changes. Sensitisation of these nerve endings, or nociceptors,
      contributes to the phenomenon of hyperalgesia, which routinely accompanies tissue
      damage. It has been shown that the acidic antipyretic analgesics reduce or down
      regulate the enhanced nociceptor sensitivity in damaged tissue, an effect
      probably attributable to inhibition of prostaglandin synthesis. Recent studies
      suggest that these drugs may have an additional mechanism of action in the spinal
      cord or higher centres. When enantiomers of flurbiprofen were used in the rat, it
      was shown that S- and R-flurbiprofen exert differential antinociceptive effects.
      The R-enantiomer, which is practically devoid of peripheral cyclo-oxygenase
      inhibitory activity in vitro, showed comparable analgesic potency to the S
      enantiomer, which does inhibit cyclo-oxygenase activity, in experimental models
      of nociception. It is possible that the antinociceptive action of the R
      enantiomer is related to a reduction in prostaglandin synthesis in the CNS rather
      than at the site of tissue damage, although other mechanisms may also contribute
      to its antinociceptive action. In contrast to earlier indications, it would
      appear that a significant part of the antinociceptive action of the antipyretic
      analgesics is exerted in the spinal cord. The observed accumulation of acidic
      antipyretic analgesics in inflamed tissue may account for the superior anti
      inflammatory activity of these latter compounds.

PMID- 7525184
TI  - Current approaches to the treatment and management of chronic lymphocytic
      leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) patients in early clinical stage (Binet A;
      Rai 0) with nondiffuse bone marrow histopathology and low stable blood lymphocyte
      levels have long survival rates and should not be treated unless the disease
      progresses. In contrast, patients with poor prognostic features, such as advanced
      clinical stage (Binet B, C; Rai III, IV), diffuse bone marrow infiltration or
      high and rapidly increasing blood lymphocyte levels, have a median survival of
      less than 5 years and need therapy. Chlorambucil is still the mainstay for CLL
      treatment. Compared with chlorambucil, combination chemotherapy produces higher
      remission rates but no increases in survival. New agents such as fludarabine and
      2-chlorodeoxyadenosine are already the treatment of choice for patients failing
      standard therapies, and their role as front-line therapy is being investigated in
      randomised trials. Whatever the treatment used, however, cure is rarely achieved.
      Certain situations (e.g. autoimmune cytopenias, hypersplenism) require special
      treatment approaches (e.g. corticosteroids, splenectomy). Bone marrow
      transplants, albeit experimental in CLL, warrant investigation in younger
      patients with poor prognosis.

PMID- 7525185
TI  - The management of follicular lymphoma.
AB  - Follicular lymphoma is demonstrably incurable with conventional treatment. A
      number of strategies have prolonged the duration of remission. However, none have
      convincingly improved survival. The following new treatment modalities are
      currently being evaluated: Interferon, given either alone, in combination with
      conventional chemotherapy or as maintenance therapy certainly has activity in
      follicular lymphoma, although its precise role remains to be defined. Myelo
      ablative therapy with autologous bone marrow transplantation, with or without in
      vitro treatment of the marrow, is showing encouraging preliminary results,
      although longer follow-up is required. The use of radiolabelled monoclonal
      antibodies is an exciting area of research, with responses being observed in
      patients in whom other treatments have failed. The purine analogues, for example
      fludarabine, are an interesting class of new compound. Once more, these are
      proving to be useful when other treatments have failed. These four treatment
      modalities are critically appraised in the present paper.

PMID- 7525183
TI  - The spinal actions of nonsteroidal anti-inflammatory drugs and the dissociation
      between their anti-inflammatory and analgesic effects.
AB  - The traditional classification of nonsteroidal anti-inflammatory drugs (NSAIDs)
      as exclusively 'peripherally acting' agents is no longer valid. For many of these
      agents there is a growing body of evidence in favour of an additional central
      mechanism for their anti-inflammatory and analgesic effects. This view is further
      supported by the recent discovery that a substantial component of the
      hyperalgesia and allodynia that characterise postinjury hypersensitivity occurs
      in the CNS, notably the spinal dorsal horn. An important corollary is that
      inhibition of central nociceptive processing may represent an important analgesic
      mode of action for those NSAIDs that are effective in the management of pain
      after tissue injury. Historically, attempts to group this heterogeneous class of
      compounds into a single entity are largely derived from the observation that the
      majority of clinically useful NSAIDs are weak organic acids (pKa 3 to 5), bind
      extensively to plasma albumin (= 99%), and inhibit (to varying degrees)
      prostaglandin synthesis. However, the significance of these various unifying
      features is becoming increasingly obscure. While inhibition of prostaglandin
      synthesis apparently remains an important analgesic mode of action for NSAIDs
      both in the periphery and the CNS, other mechanisms should be considered. Some
      NSAIDs, in addition to their effects on prostaglandin synthesis, also affect the
      synthesis and activity of other neuroactive substances believed to have key roles
      in processing nociceptive input within the dorsal horn. It has been argued that
      these other actions, in conjunction with inhibition of prostaglandin synthesis,
      may synergistically augment the effects of NSAIDs on spinal nociceptive
      processing. Despite much effort, it remains a formidable task to assess the
      significance of these differential mechanisms upon clinical pain states. In the
      meantime, however, it may be possible, on the basis of in vivo studies, to
      evaluate the impact of putative spinal analgesic mechanisms that are unrelated to
      inhibition of prostaglandin synthesis. This approach has recently been extended
      to include the identification of pharmacokinetic and clinical correlates of these
      derived in vivo parameters, and in this way attempt to demonstrate clinical
      relevance.

PMID- 7525187
TI  - Evolution of the arabinosides and the pharmacology of fludarabine.
AB  - An understanding of the pharmacokinetics of a drug is essential to the optimal
      design of the dose and schedule of chemotherapy protocols. As an extension,
      knowledge of the mechanism of drug action is necessary to construct the optimal
      strategy for combination chemotherapy. Nucleoside antimetabolites such as
      arabinosylcytosine, arabinosyladenine, and fludarabine are prodrugs that must
      enter cells and be phosphorylated to the respective triphosphates before they can
      elicit biological activity. DNA synthesis is the major metabolic target for this
      class of compounds. Common to members of the arabinosyl nucleoside class is the
      finding in experimental systems of a relationship between incorporation of each
      drug into DNA and the loss of clonogenicity. Although additional inhibitory
      mechanisms have been identified, they all require formation of the respective
      triphosphate. Thus, knowledge of the pharmacokinetics of the triphosphates in
      target cells and an understanding of the mechanisms by which these active forms
      of arabinosyl nucleosides kill cells are indispensable to the rational design of
      treatment protocols. This article considers the clinical development of
      arabinosyl nucleosides with respect to investigations of their pharmacokinetics
      and mechanisms of action. An understanding of these elements of arabinosyl
      nucleoside metabolism should provide a rationale for combinations with other
      chemotherapeutic agents and anticancer modalities.

PMID- 7525188
TI  - Clinical experience with fludarabine in leukaemia.
AB  - Fludarabine (Fludara) is a new purine analogue that was first entered into
      clinical trials in 1982. Results of initial studies with high dosages (> 96
      mg/m2/day for 5 to 7 days) of fludarabine in acute leukaemia showed significant
      cytoreductive activity but a high incidence of severe irreversible neurotoxicity.
      The results of subsequent studies with lower dosages of 25 to 30 mg/m2/day for 5
      days in chronic lymphocytic leukaemia (CLL) and low grade lymphomas have shown
      this regimen to be effective and safe, with almost no significant neurotoxicity.
      At present, the major role of fludarabine in leukaemia is in the management of
      CLL. In previously treated patients with CLL, responses are obtained in more than
      50% of patients, with two-thirds of those responses being complete remissions
      according to the National Cancer Institute Working Group (NCIWG) criteria for
      complete response and partial response. The major causes of morbidity associated
      with fludarabine in CLL are infections and febrile episodes. These occur more
      frequently in previously treated patients and those with advanced stage of
      disease. Myelosuppression is dose limiting and a small proportion of patients
      with CLL develop moderate to severe and sometimes protracted myelosuppression.
      Administration of combined fludarabine and cytarabine (cytosine arabinoside; ara
      C) alone (FA regimen) or together with granulocyte colony-stimulating factor
      (FLAG regimen) produced high response rates in previously treated refractory
      patients with acute leukaemia and previously untreated patients with acute
      myelogenous leukaemia or myelodysplastic syndrome. The wide range of biochemical
      and biological activities of fludarabine suggests that it will have an expanding
      role in future combinations in the treatment of both acute and chronic
      leukaemias.

PMID- 7525186
TI  - Immunological and genetic abnormalities in chronic lymphocytic leukaemia. Impact
      of the purine analogues.
AB  - Chronic lymphocytic leukaemia (CLL) is a disease characterised by several immune
      defects such as frequent autoimmune complications and functional T-cell defects,
      which lead to an increased risk of infections (mostly bacterial) and other
      tumours. Clonal chromosome abnormalities are identified in half of the patients,
      and trisomy 12, the most common aberration, is present in about one-third of
      patients with clonal changes. The commonest structural abnormalities involve
      chromosome 13 at band q14, the site of the retinoblastoma tumour suppressor gene.
      A gene located telomeric to the Rb1 gene, identified by the D13S25 probe, might
      be a better candidate for a pathophysiologically relevant gene in CLL, since
      repeated reports have identified homozygous deletions of this site. The purine
      analogues fludarabine and cladribine (2-chloro-2'-deoxyadenosine) and the
      adenosine deaminase inhibitor deoxycoformycin all have therapeutic effects in a
      range of lymphoproliferative disorders. Prolonged immunosuppression with low CD4
      cell counts frequently occurs and, subsequently, opportunistic infections may be
      seen. This has to be taken into consideration when treating patients with any of
      these potent drugs.

PMID- 7525189
TI  - Fludarabine in the management of malignant lymphomas.
AB  - Fludarabine has revealed significant single agent activity in non-Hodgkin's
      lymphomas (NHL) in a variety of clinical phase I/II studies. Its efficacy appears
      most pronounced in low grade NHL and the follicular subtype in particular as well
      as in Waldenstrom's macroglobulinaemia. In these disorders, response rates range
      from 31 to 67% in previously treated patients, and up to 75% in previously
      untreated patients. Intermediate and high grade NHL subtypes, as well as
      Hodgkin's disease and lymphomas of the T-cell lineage, appear less responsive.
      Further improvement may result from combination therapy such as the fludarabine,
      mitoxantrone, dexamethasone regimen. Prospective controlled clinical trials are
      needed to compare fludarabine with standard therapies and to define the most
      appropriate place for this highly promising agent in the treatment of malignant
      lymphomas.

PMID- 7525190
TI  - Potential immunological action of purine nucleoside analogues.
AB  - Purine nucleoside analogues are a new class of drugs with activity against
      nondividing lymphocytes; thus, they should play a major role in the treatment of
      low grade lymphoid malignancies. As these drugs are active against resting
      lymphocytes, harmful effects related to this action were expected and have been
      reported. However, the toxic effects on resting lymphocytes observed during
      treatment of lymphoid malignancies may potentially be of some benefit in patients
      with autoimmune diseases. To substantiate this possibility, a considerable amount
      of work needs to be carried out in order to better define the mechanism of action
      of these drugs, as well as their potential activity on different immunological
      effectors. Also, studies in animal models of autoimmune disease should be
      undertaken.

PMID- 7525191
TI  - Clinical relevance of reducing triglycerides. Implications for ischaemic heart
      disease treatment.

PMID- 7525192
TI  - Fixed-dose combination antihypertensive drugs. Do they have a role in rational
      therapy?
AB  - Fixed-dose combination antihypertensive therapy has been available for over 25
      years. During that time, considerable progress has been made in the development
      of physiologically appropriate combinations. The inherent advantage of fixed-dose
      combination therapy resides in its improving compliance because fewer pills are
      required. Alternatively, fixed-dose combination therapy limits dosage flexibility
      and dose titration of a single component of the combination to complement ongoing
      treatment of a concomitant non-hypertensive illness. The most frequently employed
      fixed-dose combinations include some form of a thiazide diuretic together with
      either a potassium-sparing diuretic, beta-blocker or an angiotensin converting
      enzyme inhibitor. Newer combinations using a calcium channel blocker and beta
      blocker, or a calcium channel blocker and an angiotensin converting enzyme
      inhibitor are either in development or soon to be available. Such developments,
      if combined with appropriate cost reductions will ultimately increase the
      popularity of these combination drug administration strategies.

PMID- 7525193
TI  - Guidelines for the rational use of benzodiazepines. When and what to use.
AB  - The main actions of benzodiazepines (hypnotic, anxiolytic, anticonvulsant,
      myorelaxant and amnesic) confer a therapeutic value in a wide range of
      conditions. Rational use requires consideration of the large differences in
      potency and elimination rates between different benzodiazepines, as well as the
      requirements of individual patients. As hypnotics, benzodiazepines are mainly
      indicated for transient or short term insomnia, for which prescriptions should if
      possible be limited to a few days, occasional or intermittent use, or courses not
      exceeding 2 weeks. Temazepam, loprazolam and lormetazepam, which have a medium
      duration of action are suitable. Diazepam is also effective in single or
      intermittent dosage. Potent, short-acting benzodiazepines such as triazolam
      appear to carry greater risks of adverse effects. As anxiolytics, benzodiazepines
      should generally be used in conjunction with other measures (psychological
      treatments, antidepressants, other drugs) although such measures have a slower
      onset of action. Indications for benzodiazepines include acute stress reactions,
      episodic anxiety, fluctuations in generalised anxiety, and as initial treatment
      for severe panic and agoraphobia. Diazepam is usually the drug of choice, given
      in single doses, very short (1 to 7 days) or short (2 to 4 weeks) courses, and
      only rarely for longer term treatment. Alprazolam has been widely used,
      particularly in the US, but is not recommended in the UK, especially for long
      term use. Benzodiazepines also have uses in epilepsy (diazepam, clonazepam,
      clobazam), anaesthesia (midazolam), some motor disorders and occasionally in
      acute psychoses. The major clinical advantages of benzodiazepines are high
      efficacy, rapid onset of action and low toxicity. Adverse effects include
      psychomotor impairment, especially in the elderly, and occasionally paradoxical
      excitement. With long term use, tolerance, dependence and withdrawal effects can
      become major disadvantages. Unwanted effects can largely be prevented by keeping
      dosages minimal and courses short (ideally 4 weeks maximum), and by careful
      patient selection. Long term prescription is occasionally required for certain
      patients.

PMID- 7525196
TI  - Trandolapril. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic use in essential hypertension.
AB  - Trandolapril is a non-sulfhydryl prodrug which, after oral administration, is
      hydrolysed in the liver to its active diacid, trandolaprilat. Trandolaprilat
      inhibits the angiotensin converting enzyme (ACE) and displays similar
      pharmacodynamic properties to other ACE inhibitors, improving haemodynamic and
      cardiac parameters in patients with essential hypertension. Trandolapril 2 to 4mg
      once daily effectively controls blood pressure for at least 24 hours in patients
      with mild to moderate hypertension. In a small number of double-blind comparative
      trials, trandolapril had similar antihypertensive efficacy to that of atenolol,
      enalapril, hydrochlorothiazide, lisinopril and sustained release nifedipine, but
      was more effective than captopril. Combined therapy with trandolapril and
      hydrochlorothiazide or sustained release nifedipine had a significantly greater
      antihypertensive effect than either drug treatment alone. Further comparative
      trials are warranted to confirm these preliminary findings. The tolerability
      profile of trandolapril is similar to that of other ACE inhibitors, most adverse
      events being generally mild and transient in nature, and trandolapril lacks
      adverse effects on carbohydrate and lipid metabolism. Thus, trandolapril, with
      its favourable pharmacological profile and antihypertensive activity similar to
      that of agents currently used to treat patients with mild to moderate
      hypertension, is likely to provide a well tolerated option for the treatment of
      this disease. The results of ongoing and future clinical trials will determine
      its potential as a cardioprotective agent in patients following myocardial
      infarction.

PMID- 7525195
TI  - Acne. A review of optimum treatment.
AB  - Acne vulgaris is a disease of the pilosebaceous unit of the skin. It may have
      profound psychological sequelae. The lesions are due to abnormally adherent
      keratinocytes causing plugging of the follicular duct followed by accumulation of
      sebum and keratinous debris. This results in the formation of the primary lesion
      of acne, the comedo. Inflammation of comedones produces papules, pustules and
      nodules, which often prompt patients to seek treatment. Various effective
      treatments include topical anti-inflammatory, antibiotic and peeling agents, oral
      antibiotics, topical and oral retinoids, and hormonal agonists and antagonists.
      Useful combination regimens are discussed, and treatment approaches suggested.
      Mild cases of comedonal acne may respond to a topical retinoid or benzoyl
      peroxide, while inflammatory lesions benefit from topical antibiotics. More
      severe inflammatory acne is treated with systemic antibiotics. Recalcitrant cases
      often require oral isotretinoin or hormonal manipulation.

PMID- 7525197
TI  - Could NSAIDs have a role as antiasthmatic agents?

PMID- 7525194
TI  - Gonadotrophin-releasing hormone agonists. A guide to use and selection.
AB  - The development of superactive analogues of gonadotrophin-releasing hormone
      (GnRH) represents one of the most important new pharmaceutical contributions of
      the last 2 decades. This class of drugs is now available worldwide and is
      successfully employed in the management of precocious puberty, ovulation
      induction, prostatic cancer, premenopausal breast cancer, endometriosis, uterine
      leiomyoma, and for the preparation of female patients undergoing laparotomic,
      vaginal or endoscopic surgery. GnRH agonists are also applied with some success
      in other clinical conditions such as catamenial disorders, hyperandrogenism and
      menometrorrhagia. Studies are under way to identify other potential clinical
      applications such as other forms of cancer.

PMID- 7525199
TI  - Effects of lindane exposure on rainbow trout (Oncorhynchus mykiss) immunity. I.
      Effect of lindane on antibody-secreting cells (ASC) measured by ELISPOT assay.
AB  - Yersinia ruckeri vaccine was injected in rainbow trout 7 days after ip
      contamination with 10, 50, or 100 mg lindane per kilogram body weight. The
      antibody-secreting cells measured by ELISPOT assay were affected by the
      insecticide, slightly for 10 mg and strongly for higher concentrations.
      Consequently the antibody production in sera, measured by agglutination, was
      suppressed.

PMID- 7525200
TI  - Tissue repair: a critical determinant in CCl4 hepatotoxicity.
AB  - A single antimitotic dose of colchicine administered 24 hr after a single ip dose
      of CCl4 profoundly enhanced lethality in the adult Sprague-Dawley male rat from <
      10% to over > or = 70% within the next 24 hr. These findings suggest that
      disruption of normal hepatic cellular repair processes is a critical factor
      affecting the outcome of CCl4 intoxication.

PMID- 7525201
TI  - Phototoxicology. 1. Light-enhanced toxicity of TNT and some related compounds to
      Daphnia magna and Lytechinus variagatus embryos.
AB  - Many environmental pollutants interact with solar near-ultraviolet (nuv) light in
      a manner which greatly increases their toxic effects. The phenomenon of light
      mediated toxicity (phototoxicity) is only now becoming generally recognized to
      any significant degree. Manufacture of, and loading munitions with, the explosive
      2,4,6-trinitrotoluene (TNT) in past decades caused contamination of soils and
      sediments at levels exceeding 1000 ppm and of waters at levels near saturation
      (100 ppm). Manufacture of TNT produces numerous nitrated by-products, and most of
      these compounds, including TNT, can be metabolized by many species, including
      bacteria, fungi, plants, and mammals. This study investigated the phototoxicity
      of TNT, and 2,3-, 2,4-, 2,6-, and 3,4-dinitrotoluene (DNT) and -diaminotoluene
      (DAT), and the major metabolites 2-amino-4,6-dinitrotoluene (2A) and 4-amino-2,6
      dinitrotoluene (4A), to Daphnia magna (acute toxicity) and Lytechinus variagatus
      (sea urchin) embryos (subacute, developmental toxicity). Most of the compounds
      were weakly toxic or nontoxic in the dark. All were phototoxic to sea urchins. In
      D. magna, 2,3- and 3,4-DNT/DAT and 4A were not toxic but were phototoxic, and 2A
      was toxic and phototoxic; the other isomers were not toxic or phototoxic to this
      species.

PMID- 7525202
TI  - Phototoxicology. 2. Near-ultraviolet light enhancement of Microtox assays of
      trinitrotoluene and aminodinitrotoluenes.
AB  - Coexposure of 2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2A), or 4
      amino-2,6-dinitrotoluene (4A) to near-ultraviolet (nuv) light (lambda max-354 nm)
      significantly enhanced their toxicity toward Photobacterium phosphoreum (Microtox
      bioassay) during 30 min but not 15 min. Based on the slopes of the dose-response
      lines, the nuv coexposure and dark toxic mechanisms of action for TNT, 2A, and 4A
      appeared to be similar. nuv coexposure of binary mixtures significantly enhanced
      (supraadditivity) the toxicity of these compounds to P. phosphoreum. Under normal
      laboratory lighting, the toxicity of TNT + 2A and 2A + 4A mixtures were
      supraadditive but the toxicity of TNT + 4A mixtures could be explained by simple
      addition. Supporting these conclusions, the response curves of alpha-terthienyl,
      a compound known not to require nuv for toxicity, were similar in the dark and
      with nuv coexposure. In contrast, angelicin and psoralen, compounds known to
      require nuv coexposure to damage DNA, gave response curves having different
      slopes in the dark and with nuv coexposure. The nuv coexposure Microtox assay was
      able to detect and quantify phototoxicity in psoralen, angelicin, alpha
      terthienyl, anthracene, TNT, and aminodinitrotoluenes.

PMID- 7525203
TI  - Phototoxicology. 3. Comparative toxicity of trinitrotoluene and
      aminodinitrotoluenes to Daphnia magna, Dugesia dorotocephala, and sheep
      erythrocytes.
AB  - 2,4,6-Trinitrotoluene (TNT) and compounds associated with its production are
      toxic and phototoxic to a wide range of biota. The planarian Dugesia
      dorotocephala, but not Daphnia magna, metabolized TNT (1 mg/liter) to 4-amino-2,6
      dinitrotoluene (4A; 0.4 mg/liter) and 2-amino-4,6-dinitrotoluene (2A; 0.2
      mg/liter). Coexposure to near-ultraviolet (nuv) light enhanced the toxicity of 2A
      more than that of TNT and 4A. The toxicities of TNT, 4A, and 2A to Du.
      dorotocephala were all decreased by glutathione (GSH) conjugation. This suggests
      that all had mechanisms of toxic action involving formation of quinone-GSH
      conjugates. Dark and light mechanisms for TNT and 2A depended on GSH conjugation,
      but the specific mechanisms may be different for each compound. The dark and
      light mechanisms of toxic action for 4A appeared to be fundamentally different in
      that the dark toxic mechanism of action was less dependent on GSH conjugation.
      Hemolysis studies using sheep erythrocytes showed that the light-enhanced toxic
      mechanism of action for TNT, 2A, and/or 4A did not involve cellular membrane
      damage in response to nuv-induced anions.

PMID- 7525204
TI  - Effects of elevated selenium concentration on selenium accumulation and nitrogen
      fixation symbiotic activity of Melilotus indica L.
AB  - Biological and soil factors which contribute to the successful colonization of an
      annual legume species. Melilotus indica L., in soils with elevated selenium (Se)
      were studied. This species was introduced into the Kesterson Reservoir in the
      fresh top soil that was brought in under the Kesterson Cleanup Action to fill
      lowering pond sites and prevent the formation of ephemeral pools containing
      hazardous levels of Se. In 4 years since its introduction, it has expanded its
      range of colonization from the fresh soil fill sites to the native soil sites and
      contributed 10 to 50% of biomass to the grassland communities. The plant and
      nodule tissue Se concentrations of the field grown plants were found to be
      negatively correlated with the soil sulfate concentration. Nutrient solution
      culture studies discovered that M. indica was able to accumulate 500 micrograms
      Se g-1 dry weight without a reduction of growth rate. Plants without nodulation
      were found to accumulate a greater amount of Se and more vulnerable to Se
      toxicity. Acetylene reduction rate measurements indicate that the nitrogen
      fixation symbiotic activity appears to be more susceptible to an elevated Se
      concentration than its host plant. M. indica is a winter weed, and it occurs
      naturally in the Se-rich soils. It grows actively over the winter and spring and
      complete its life cycle in May. If the root nodules and root tissues are
      incorporated into the soil, the rate of soil Se volatilization may be accelerated
      over the warm summer months. For disposal of the Se-rich plant materials the
      plant shoot tissues may be harvested for Se-deficient forage supplementation.
      Therefore, this species may be useful for field management and reclamation of Se
      contaminated soils.

PMID- 7525205
TI  - Biotests using unicellular algae and ciliates for predicting long-term effects of
      toxicants.
AB  - Test systems for predicting long-term effects with the freshwater algae
      Chlamydomonas reinhardi and Scenedesmus subspicatus and the ciliate Tetrahymena
      pyriformis were evaluated with respect to the following reference chemicals:
      atrazine, bromacil, diuron, methyl parathion, lindane, 3,4-dichloroaniline,
      pentachlorophenol, cadmium, copper, and the volatile 1,2-dichloropropane. In
      growth-inhibition tests under static conditions the algae revealed a higher
      sensitivity to the toxicants than the ciliate except for lindane and methyl
      parathion. Comparison of the impairment of photosynthetic efficiency (EPR, NOEC
      24 hr) with the inhibition of growth (NOEC 72 hr) of S. subspicatus revealed a
      higher sensitivity of the EPR parameter for inhibitors of the photosynthesis. A
      flowthrough system was developed for long-term tests and testing of volatile and
      instable substances. Under flowthrough conditions C. reinhardi was more
      susceptible to the chemicals than under static test conditions, except for
      pentachlorophenol. Due to the high volatility, 1,2-dichloropropane was only
      tested in the flowthrough system. The data obtained from these toxicity tests
      provide information about effects on organisms representing different levels of
      the aquatic food web, possessing differences in sensitivity against toxicants.
      The presented flowthrough system allows the testing of volatile and instable
      chemicals, problematic in static test systems, and the EPR parameter is suitable
      for the early characterization of chemicals acting as specific inhibitors of the
      photosynthetic electron transport chain.

PMID- 7525206
TI  - Uptake and toxicological effects of some heavy metals on Pleurotus sajor-caju
      (Fr.) singer.
AB  - The uptake of heavy metals at sublethal concentrations by the mycelia and
      sporocarps of an edible fungus Pleurotus sajor-caju was measured by an atomic
      absorption spectrophotometer, and their impact on growth, productivity, and
      cellular proteins was also studied. Mycelia demonstrated the lowest uptake of
      Co2+ (11 micrograms ml-1) and Hg2+ (12 micrograms ml-1) and the highest uptake of
      Cu2+ (182 micrograms ml-1) and Cd2+ (178 micrograms ml-1). Sporocarps obtained
      from the substrate treated separately with Pb2+ (100 micrograms ml-1) and CD2+ (6
      micrograms ml-1) indicated a minimum and maximum uptake of Pb2+ (7 micrograms g
      1) and Cd2+ (33 micrograms g-1), respectively. Although Cu2+ and Cd2+ at 6
      micrograms ml-1 indicated 41 and 93% growth reduction, Pb2+ and Hg2+ also caused
      more than 85% reduction of growth at 15 and 6 micrograms ml-1, respectively. Pb2+
      reduced mycelial protein significantly (36%), but Hg2+ caused maximum reduction
      (30%) of proteins in sporocarps. Separate treatment of spawned substrate with
      test heavy metals reduced biological efficiency of sporocarp production, but
      markedly with Pb2+.

PMID- 7525207
TI  - Effect of sublethal concentrations of pesticides on the feeding behavior of
      Daphnia magna.
AB  - Daphnia magna was exposed to sublethal levels (1/4, 1/2, and 2/3 LC50 and LC50)
      of endosulfan and diazinon to determine the effect of these pesticides on
      filtration and ingestion rates. The experiments were performed with the
      unicellular algae Nannochloris oculata in a density of 5 x 10(5) cells/ml. Prior
      to these experiments, the acute toxicity of both pesticides was evaluated to
      calculate the LC50s. The 24-hr LC50 values were 0.62 mg/liter and 0.9
      microgram/liter for endosulfan and diazinon, respectively. Rates of filtration
      and ingestion declined with increasing toxicant concentrations after a short
      exposure of 5 hr. The effective concentration at which feeding rates were reduced
      to 50% of those in controls (EC50) was calculated for both pesticides. These
      values were 0.44 and 0.61 mg/liter for filtration and ingestion rates,
      respectively, in the case of endosulfan and 0.47 and 0.60 microgram/liter,
      respectively, in the case of diazinon.

PMID- 7525209
TI  - Influence of enzyme levels on the toxicity and in vitro metabolism of 2,2',5
      trichlorobiphenyl in houseflies.
AB  - Adult female houseflies (Musca domestica) were topically dosed with 10, 15, and
      20 micrograms of 2,2',5-trichlorobiphenyl (PCB-18) in acetone at 1, 5, and 15
      days following emergence. These doses caused a significant decrease in the mean
      survival time in 5-day-old flies. LT50's (time for 50% death) were dramatically
      reduced in 5-day-old flies, whereas no significant difference was found at any
      treatment level in 15-day-old flies. Abdomenal microsomal enzyme levels were
      determined by the rate of O-dealkylation of (p-nitrophenyl)ethyl ether for 1-, 5
      , 11-, and 15-day-old female houseflies. The highest levels were found in 5-day
      old flies and the lowest in 15-day-old flies. The greatest metabolism of PCB-18
      by housefly microsomes also occurred in 5-day-old flies. The enzyme levels,
      metabolism, and toxicity suggest that PCB-18 is bioactivated to a product(s)
      which reduces the mean survival time of houseflies.

PMID- 7525198
TI  - Omeprazole. An update of its pharmacology and therapeutic use in acid-related
      disorders.
AB  - Omeprazole, a gastric acid pump inhibitor, dose-dependently controls gastric acid
      secretion: the drug has greater antisecretory activity than histamine H2-receptor
      antagonists. Omeprazole 20 to 40 mg/day is more effective than histamine H2
      receptor antagonists in the short term treatment of duodenal ulcer, gastric ulcer
      and reflux oesophagitis. Available data suggest that omeprazole 10 to 40 mg/day
      is also more effective than ranitidine in the maintenance therapy of duodenal
      ulcer and reflux oesophagitis. The drug is also effective in patients with
      duodenal ulcer, gastric ulcer or reflux oesophagitis poorly responsive to
      histamine H2-receptor antagonists. The efficacy of omeprazole 20 mg/day appears
      to be similar to that of lansoprazole 30 mg/day in the short term treatment of
      duodenal ulcer, gastric ulcer and reflux oesophagitis. However, most available
      studies have been reported in abstract form only, and 2 of 3 studies in patients
      with duodenal ulcer have shown greater healing rates at 2 (but not 4) weeks with
      lansoprazole. Helicobacter pylori eradication decreases duodenal ulcer relapse
      rates and appears to be associated with improved duodenal ulcer healing rates.
      Evidence also suggests that H. pylori eradication is associated with reduced
      gastric ulcer relapse rates. Omeprazole monotherapy may suppress but does not
      eradicate H. pylori infection. Eradication rates with omeprazole 20 or 40 mg
      twice daily plus amoxicillin usually up to 2 g/day (3 g/day in a few studies) for
      2 weeks appear to be similar to those of standard triple therapy (bismuth salt
      plus metronidazole, plus tetracycline or amoxicillin) or omeprazole plus
      clarithromycin, although eradication rates vary widely. Omeprazole plus
      amoxicillin appears to be better tolerated than triple therapy and represents a
      first-line treatment alternative in patients with H. pylori-associated peptic
      ulcer disease. Omeprazole plus amoxicillin plus metronidazole appears to be more
      effective than omeprazole plus amoxicillin in patients with metronidazole
      sensitive H. pylori infection. Omeprazole remains a treatment of choice in
      patients with Zollinger-Ellison syndrome. The dosages should be adjusted
      according to individual response. However, relatively low dosages of 10 to 40
      mg/day may be sufficient in some patients. The drug has also shown promise in the
      treatment of children with severe reflux oesophagitis, in patients with reflux
      oesophagitis and coexisting systemic sclerosis, and in the prevention of
      aspiration pneumonia. Evidence suggests that omeprazole is more effective than
      ranitidine in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced
      gastric damage who continue to take NSAIDs, especially in patients with large
      gastric ulcers; however, completion of ongoing studies is required to verify
      this.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525211
TI  - Review of heavy metals in the African aquatic environment.
AB  - Data were compiled from selected heavy metal studies in both freshwater and
      marine ecosystems from the major African subregions, Northern, West and Central,
      Eastern, and Southern Africa. The concentrations of heavy metals were compared
      between different environmental compartments (water, sediments, fauna, and
      flora), between the different African subregions and with data from other areas
      in the world. Despite the scarcity of the existing information on Africa, some
      conclusions could be drawn: Metal concentrations in organisms were generally
      below WHO limits except for some localized sites, mostly with increased lead
      levels. There were no significant differences between inland water and coastal
      animals, but shellfish had higher concentrations of most metals than finfish. For
      aquatic plants the heavy metal levels were higher in inland waters. Compared to
      more industrialized regions and with the exception of some hot-spot sites, the
      concentrations of heavy metals in African aquatic systems were low and close to
      natural background levels. Nevertheless, in view of the expected increase in
      urbanization and socio-economic activities in Africa, sources and quantities of
      heavy metal discharges to aquatic environments have to be identified. Also,
      pollution control measures should be formulated in each country.

PMID- 7525208
TI  - Uptake pathways of chlorobenzenes in plants and their correlation with N
      octanol/water partition coefficients.
AB  - The bioconcentration factors of 14C-labeled chlorinated benzenes in plants from
      soil were quantified in short-term laboratory experiments and correlated to Kow.
      The correlation was negative for barley and positive for cress. In order to
      interpret these opposite results, the log/log correlation between partition
      coefficients and Kow of the chemicals was established also for each step of the
      uptake, via both roots and leaves. For the first step of root uptake--the
      partition of the chemicals from soil solids into soil water--the correlation with
      Kow was negative, whereas it was positive for the second step, the partition
      roots/soil water, of both plant species. Similarly, the correlation between the
      first step of foliar uptake--the partition of the chemical from soil into air-
      and Kow was negative, and that between the second step--the partition between
      aerial plant parts and air--and Kow was positive for both plant species. The
      slopes of the regression lines differed between plant species. It may be
      concluded that Kow can be used as a parameter to predict the uptake of chemicals
      from soil by plants only if the same class of chemicals and the same plant
      species is considered.

PMID- 7525210
TI  - Photosynthesis inhibition by phenylureas: a QSAR approach.
AB  - A series of 21 N'-phenyl-N,N-disubstituted ureas was studied for its effects on
      thylakoidal electron transfer, photophosphorylation, and photosynthetic O2
      evolution in class A chloroplasts and leaf fragments. The concentrations of test
      compounds that produced 50% inhibition of PS II electron transfer and of
      photosynthesis in class A chloroplasts were highly correlated. Urea derivatives
      with a N-lipophilic substituent (three or four carbon chains) were uncouplers
      (i.e., neburon uncoupled by 50% at 7 microM). The efficiency of inhibition of PS
      II electron transfer was increased by the presence of a 3,4-disubstitution of the
      phenyl ring. The presence of N-lipophilic substituents was necessary for there to
      be an inhibitory effect, but an increase in the length of the chain lowered the
      activity. The best QSAR equations that described the inhibitory activity of the
      whole series were obtained when using 1 chi v or MR (probably representing
      dispersion forces) associated with parameters that described the steric hindrance
      at the p position of the phenyl ring (Verloop's B2(4), B4(4)) or in its
      neighborhood (such as the angular parameter A4). The inhibitory efficiency of the
      phenylurea series on wheat and spinach pieces led to the conclusion that some
      extrachloroplastic factors seemed to limit the accessibility of the D1-protein
      target.

PMID- 7525213
TI  - Xenobiotic-metabolizing enzyme systems in test fish. V. Comparative studies of
      liver microsomal glucuronyltransferases.
AB  - UDPG-glucuronyltransferase (GT) activities have been determined in the hepatic
      microsomes of fish species recommended by OECD for some (eco)toxicological tests.
      Due to the heterogeneity of this enzyme family, different chemicals were used as
      substrate: 4-nitrophenol (4NP), 4 methylumbelliferone (4MU), and 2- and 4
      hydroxybiphenyl (2OHB and 4OHB). The 4NP-GT and 2OHB-GT activities of hepatic
      microsomes from all the species were linearly dependent on the substrate
      concentration (tested concentrations up to 2 and 0.5 mM, respectively). 4OHB-GT
      and 4MU-GT demonstrated different degrees of saturation in the range of substrate
      concentrations 0-0.5 mM and 0-0.3 mM, respectively. Specific activities ranged
      among the species usually within a factor of about 3. The highest ratios (up to
      10) were occasionally found for 4MU-GT (between trout and golden orfe) and 2OHB
      GT (between guppy and carp, zebra fish, or trout). These results confirm that GT
      activities in fish are much lower than in mammals.

PMID- 7525214
TI  - Statistical analysis of joint toxicity in biological growth experiments.
AB  - The authors formulate a model for the analysis of designed biological growth
      experiments where a mixture of toxicants is applied to biological target
      organisms. The purpose of such experiments is to assess the toxicity of the
      mixture in comparison with the toxicity observed when the toxicants are applied
      individually to the organisms. The analysis is based on a random differential
      equation describing the growth of the organisms. This model yields a natural
      measure of interaction between toxicants and the hypothesis of independent action
      from a mixture of toxicants can be tested. The proposed model is applied on data
      from an experiment where inhibition of the growth of the bacteria Pseudomonas
      fluorescens caused by different mixtures of pentachlorophenol and aniline was
      studied.

PMID- 7525212
TI  - Photoinduced toxicity of three polycyclic aromatic hydrocarbons (fluoranthene,
      pyrene, and naphthalene) to the duckweed Lemna gibba L. G-3.
AB  - The authors recently demonstrated that light dramatically enhances the hazards of
      three polycyclic aromatic hydrocarbons (PAHs), anthracene, phenanthrene, and
      benzo[a]pyrene, to the duckweed Lemna gibba L. G-3 (X.-D. Huang, D. G. Dixon, and
      B. M. Greenberg, 1993, Environ. Toxicol. Chem., 12, 1067-1077). To extend this
      research, growth and chlorosis were used as end points to assess the photoinduced
      toxicity of three additional PAHs, fluoranthene, pyrene, and naphthalene, to L.
      gibba in the presence of simulated solar radiation (a light source with a UV-B:
      UV-A:visible light ratio equivalent to that of sunlight). The phytotoxicity of
      these three PAHs was photoactivated, with ultraviolet radiation being the only
      spectral region that enhanced the harmful effects of the chemicals. Dose-response
      curves based on chemical concentration and light intensity revealed that the
      order of phytotoxic strength was fluoranthene > pyrene > naphthalene. To explore
      whether photomodification (in addition to photosensitization) of fluoranthene,
      pyrene, and naphthalene could contribute to photoinduced toxicity, the chemicals
      were irradiated prior to (as opposed to simultaneously with) application to the
      plans. The rates of photomodification of the three PAHs were rapid enough for the
      photooxidized compounds to contribute to toxicity, and the photomodified PAHs
      were more toxic than the parent compounds. As well, toxicity could be correlated
      to photomodification; impacts increased in parallel with the extent of
      photomodification.

PMID- 7525215
TI  - Dissipation and movement of acaricide chlorobenzilate in the environment.
AB  - The dissipation of acaricide chlorobenzilate in selected soil and river water
      samples was studied. Under incubation conditions at 25 degrees C and 90% field
      capacity of moisture for 21 days, the residues of chlorobenzilate were 14 and 55%
      in Lukang silty clay loam and Pincheng clay, respectively. More than 80% of
      chlorobenzilate remained in the natural water (pH 7.2 and 7.3, respectively) and
      in the water adjusted to pH 5.0 when water samples collected from Green Lake and
      Wai-Shuang River near Taipei were treated with chlorobenzilate and then incubated
      for 34 days. But when the pH was adjusted to 9.0, only 60% was found in Green
      Lake water and 29% in Wai-Shuang River water. The dissipation of chlorobenzilate
      in the soil was fitted to first-order kinetics with half-lives of 5 to 36 days
      under various conditions in the laboratory experiments. No chlorobenzilate was
      detected in the leachate by a leaching experiment on the soil column for 18 days;
      most chlorobenzilate remained in the upper 3 cm of the column. According to
      assessment by the groundwater pollution-potential model (GWP), chlorobenzilate
      seemed to be safe in regard to groundwater contamination.

PMID- 7525218
TI  - Pesticide bioaccumulation in cattle.
AB  - A simple partition model was developed to evaluate the bioaccumulation of
      chlorinated hydrocarbon pesticides (dieldrin and heptachlor) in the soil-pasture
      grazing animal system. Biomagnification factors (BFL) calculated on a lipid basis
      ranged from 0.115 to 0.175, but could not be directly compared with other values
      from the literature because of different methods of calculation. The partition
      model predicted values of somewhat less than unity, indicating that it does not
      fully account for pesticide pathways and mechanisms. However, the lack of
      variation of these values from two compounds indicates a lack of dependence on
      the octanol/water coefficient which is in accord with the model. The results
      suggest partitioning between food in the stomach and body tissues is a major
      bioaccumulation process but other major processes are also involved.

PMID- 7525216
TI  - Gap junction-mediated intercellular communication in primary cultures of rainbow
      trout hepatocytes.
AB  - Gap junction-mediated intercellular communication was evaluated in primary
      cultures of rainbow trout hepatocytes by measurement of dye coupling. Donor
      hepatocytes were microinjected with fluorescent Lucifer yellow CH dye and
      visualization of dye spread (dye coupling) to adjacent hepatocytes was recorded.
      A maximum level was reached between 8 and 12 hr which was maintained up to 24 hr.
      Dye coupling then decreased over the next 48 hr. Cell viability was monitored by
      the percentage of total LDH released and trypan blue exclusion at each time
      point. The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), a known
      inhibitor of rodent hepatic intercellular communication, on gap junction-mediated
      intercellular communication was evaluated in 24-hr cultures. A dose-response
      inhibition was demonstrated with maximum inhibition observed at 3 hr of exposure.

PMID- 7525219
TI  - Effects of simulated oil exposure on two intertidal macrozoo benthos:
      Tympanotonus fuscata (L.) and Uca tangeri (Eydoux, 1935) in a tropical estuarine
      ecosystem.
AB  - The impacts of simulated Nigerian light crude oil on mud flat periwinkles,
      Tympanotonus fuscata (L.), and fiddler crabs, Uca tangeri (Eydoux, 1935) was
      examined through field experiments conducted in the Bonny estuary of the Niger
      Delta (southern Nigeria). The purpose was to assess the fate and effects of a
      known quantity of the Nigerian light crude oil on this environment. Drastic
      changes in the densities of T. fuscata and U. tangeri observed immediately after
      spills was attributed to the effects of the oil. A large increase in Uca biomass
      occurred in the affected area. Salinity and temperature in the study area showed
      little fluctuations throughout the survey. Sediment characteristics were similar
      for all sites (stations). Grain-size analysis revealed that sediments at the
      study area were 70% silt. Migration of oil via tidal percolation was observed as
      much as 11 cm beneath the sediment surface.

PMID- 7525217
TI  - Sediment core versus grab samples: evaluation of contamination and toxicity at a
      DDT-contaminated site.
AB  - Four sites from a stream system near Huntsville, Alabama, contaminated with DDT
      and its metabolites, were sampled using a coring device. Grab samples were also
      collected at these and five other sites. Analytical and toxicological evaluations
      were made on both sets of samples. Core samples provided vertical delineation of
      toxicity and contamination in sediments, and documented periods of sedimentation
      with clean material, which appears to be isolating the contaminated sediments
      from benthic communities. Grab samples yielded less information about the sites.
      Relationships between DDT concentration and sediment toxicity to Chironomus
      tentans were similar regardless of the sampling method. Substantial increases in
      toxicity occurred in most samples when concentrations exceeded 3000 micrograms of
      DDT residue/g organic carbon.

PMID- 7525220
TI  - Ecotoxicological studies with the freshwater rotifer Brachionus calyciflorus. IV.
      Rotifer behavior as a sensitive and rapid sublethal test criterion.
AB  - The swimming behavior of the freshwater rotifer Brachionus calyciflorus exposed
      to copper (Cu), pentachlorophenol (PCP), 3,4-dichloroaniline (DCA), and lindane,
      for periods ranging from 5 min to 5 hr, was examined. A swimming behavior test is
      described which is based on the rotifers' movement rates as they swim over a
      grid. For all four toxicants a clear dose-response was observed, with the
      swimming activity decreasing with increasing toxicant concentrations. For Cu the
      EC50's, the concentration that reduced the swimming activity to 50% of that of
      the control value, sharply decreased from 0.22 mg/liter after an exposure of 5
      min to 0.068, 0.038, and 0.014 mg/liter after exposures of 30, 60, and 300 min,
      respectively. PCP affected the rotifers' swimming behavior more gradually, with
      EC50's decreasing from 7.0 mg/liter after an exposure of 5 min to 5.9, 5.4, and
      1.5 mg/liter after 30, 60, and 300 min, respectively. A similar pattern was found
      for DCA with EC50's ranging from 193 to 45.5 mg/liter for the 5-min and 3-hr
      exposures, respectively. Exposed to lindane however, B. calyciflorus swimming
      activity exhibited a different response, and the EC50's gradually increased from
      13.7 mg/liter after an exposure of 5 min to significantly higher values of 16.4
      and 18.5 mg/liter after periods of 1 and 5 hr, respectively. The results of the
      swimming activity assays were compared to those of acute and chronic toxicity
      tests performed with the same test species. The potential use and relevance of
      this behavioral test criterion were evaluated and discussed.

PMID- 7525221
TI  - Distribution of polycyclic aromatic hydrocarbons (PAHs) in an urban roadway
      system.
AB  - The distribution of PAHs in soil, leaf litter, vegetation, soil fauna, and litter
      fauna in a roadside environment in Brisbane, Australia, was measured using gas
      chromatography and gas chromatography coupled with mass spectrometry. Sixteen
      common environmental PAHs were found to be widely distributed with leaf litter
      exhibiting the highest concentrations (1254 ng/g total wet wt). The carcinogenic
      PAHs benzo(a)anthracene, chrysene, benzo(a)pyrene, benzo(e)pyrene,
      benzo(k)fluoranthene, and indeno(1,2,3-c, d)pyrene constituted about half the
      total. Lipid content was positively correlated with total PAH content in the soil
      and leaf litter as was organic carbon content with leaf litter alone. The PAH
      content of leaf litter, soil, and vegetation declined exponentially with distance
      from the roadway, soil depth, and vegetation height, respectively. This decline
      was not related to the physicochemical characteristics of the compounds,
      suggesting that dispersal occurred as particulates with sorbed PAHs.

PMID- 7525223
TI  - Bioconcentration of polychlorinated biphenyls (PCBs) in rainbow trout caged in
      the River Po.
AB  - Two groups of rainbow trout were caged in the River Po upstream and downstream of
      the confluence with the River Lambro, a relatively small tributary which drains
      the most industrialized and urbanized area of the entire basin. Fish were
      analyzed for PCB concentration at the start of the experiment and after 7, 15,
      and 30 days of exposure. The results demonstrate that the emission of the River
      Lambro represents an important point source of PCBs to the River Po and that part
      of the transported load is readily bioavailable, since caging virtually excluded
      trophic transfers. On the basis of PCB levels measured in downstream trout, the
      steady-state concentration and the congener pattern were predicted by means of a
      computer program. These projections were compared with published data obtained
      with native fish caught downstream from the River Lambro.

PMID- 7525222
TI  - Experimental study of inorganic and methylmercury bioaccumulation by four species
      of freshwater rooted macrophytes from water and sediment contamination sources.
AB  - An experimental study based on four species of rooted macrophytes (Elodea densa,
      Ludwigia natans, Lysimachia nummularia, Hygrophila onogaria) was carried out to
      quantify and compare their mercury bioaccumulation capacity from the water column
      and the sediment compartments as initial sources of contamination. The first
      stage consisted of analyzing plant growth (weight and total length) in relation
      to six different characteristics of the biotopes, resulting from the combination
      of three types of sediment (natural sediment, sediment+sand, clay) and two types
      of aquatic medium (synthetic river water, dechlorinated tap water). This
      preliminary experiment permitted selection of the basic structure of the
      experimental units--a mixed biotope consisting of dechlorinated tap water and a
      mixture of natural sediment+sand--for the comparative analysis of mercury
      bioaccumulation capacities. In the second stage, two chemical forms of mercury
      were considered (HgCl2 and CH3HgCl), the metal being introduced into the sediment
      at the beginning of the experiment ("sediment" source) or into the water column
      by twice-daily additions ("water" source). Results showed very great accumulation
      differences after 18 or 21 days exposure: (a) Hg concentrations in the plants
      (stems+leaves) were always greater when the metal was introduced in organic form,
      with even greater differences when initial contamination was via the sediment;
      (b) according to the selected experimental conditions, mercury bioaccumulation by
      the macrophytes from the water source was about 10 times greater than that
      observed when the metal was introduced into the sediment, and thus, despite the
      strong differences between the contamination levels of these two sources, in
      favor of the sediment (factor close to 10(3) for the two compounds); and (c)
      major interspecies differences emerged in Hg burdens accumulated by the plants,
      with differences being very small when results were expressed as concentrations,
      thus taking account of the different biomasses of the species.

PMID- 7525224
TI  - Critical internal and aqueous lethal concentrations of chlorobenzenes with the
      crab Portunus pelagicus (L).
AB  - The toxicity of a series of chlorobenzenes to juvenile crabs Portunus pelagicus
      (L) was investigated. These compounds are lipophilic with a strong capacity to
      bioconcentrate. An increase in toxicity during molting was observed. There was
      also an increase in toxicity with increasing log Kow and molecular weight, which
      was best described using nonlinear regression equations relating LC50 and log
      Kow. Chlorobenzene residues in animals that died from the exposures were measured
      and the critical internal lethal concentration and volume fraction were estimated
      for each compound. A mean concentration value of 3.24 mumol g-1 on a wet weight
      basis and a mean volume fraction of 0.140 cm3 toxicant cm-3 tissue lipid were
      determined at time zero. However, these values decreased with increasing periods
      of exposure according to first-order kinetics with a constant rate of 0.0287 hr
      1. This indicates that toxicity is a function of both concentration in the
      tissues and the period during which it has been present. The critical internal
      lethal concentrations measured in this study were not consistent with the
      constant critical internal concentration/critical volume fraction hypotheses.

PMID- 7525226
TI  - The environmental risks of industrial waste disposal: an experimental approach
      including acute and chronic toxicity studies.
AB  - The toxicity of 15 leachates of various solid industrial wastes accepted in an
      engineered landfill has been studied. A cost-effective battery of tests allowing
      evaluation of acute and chronic toxicity, as well as genotoxicity, and
      investigations on different trophic levels in the aquatic environment has been
      used. Acute toxicity was tested on bacteria (Microtox assay with Photobacterium
      phosphoreum) and microcrustaceans (Daphnia magna immobilization assay). A growth
      inhibition test of microalgae was carried out on Raphidocelis subcapitata. A 28
      day chronic test with Daphnia magna was used to detect effects on reproduction.
      Genotoxicity was evaluated by means of the Ames test conducted on the crude
      aqueous phase and also on the concentrated fractions of water-extractable
      micropollutants (liquid-liquid and freeze-dried extracts). Chemical analyses of
      leachates were carried out simultaneously. The toxicity varied greatly between
      the different wastes. Toxic effects were observed in the short and/or in the long
      term. Four samples were potentially genotoxic. In most cases, toxicity registered
      could not be correlated with results of the chemical analyses. This study
      demonstrates the usefulness of associating a toxicological monitoring with
      chemical analyses in waste management.

PMID- 7525225
TI  - Atrazine toxicity on hydromineral balance of fish, Tilapia mossambicus.
AB  - The chronic effects of atrazine on total body weight, hydration level, and serum
      inorganic electrolytes in the tissues of freshwater fish, Tilapia mossambicus,
      were studied. Significant changes were observed in the tissues indicating the
      disturbances in the hydromineral balance of the fish as a consequence of
      atrazine.

PMID- 7525227
TI  - Early life-stage effects in medaka (Oryzias latipes) following in ovo exposure to
      polyamine biosynthetic inhibitors.
AB  - Medaka, Oryzias latipes, were exposed in ovo to the polyamine (PA) biosynthesis
      inhibitors alpha-difluoromethylornithine (DFMO) and methylglyoxal
      bis(guanylhydrazone) (MGBG). In an additional group, spermine, the end product of
      the PA pathway, was added with DFMO and MGBG for a "rescue" treatment. At 4 days
      posthatch, length, DNA and RNA content, and swimming endurance were measured. The
      only parameter affected by treatment was swimming endurance which revealed
      decreased latent time to fatigue with increased dose, although not statistically
      significant. The rescue group, however, did demonstrate a statistically
      significant decrease in fatigue latency as compared to controls.

PMID- 7525231
TI  - Scalp recorded direct current potential shifts associated with the transition to
      sleep in man.
AB  - Cortical direct current (DC) potentials are considered to reflect the state of
      cortical excitability which may change characteristically from wakefulness to
      sleep. The present experiments examined changes in the scalp recorded DC
      potential in 10 healthy humans at the transition from wakefulness to nocturnal
      sleep. For each subject, DC recordings obtained from Cz were evaluated for a 15
      min pre-sleep onset interval and for a 20 min post-sleep onset interval, on 2
      separate nights. Sleep stages were determined from standard sleep recordings. The
      transition from wakefulness to sleep coincided with a significant (P < 0.05)
      shift in the DC potential of negative polarity. Maximum negative potentials of
      (mean +/- S.E.M.) 500 +/- 130 microV (first night) and of 760 +/- 200 microV
      (second night) were reached at the end of the 20 min post-sleep onset interval. A
      number of possible technical and biological artifacts were controlled. It is
      reasonable to assume that the slow negative shift of the DC potential at the
      transition from wakefulness to sleep reflects increased cortical excitability.
      Whether the negative potential shift pertains during sleep, or is of transient
      nature and closely linked to the process of falling asleep, remains to be
      clarified.

PMID- 7525229
TI  - Prevalence of bilateral partial seizure foci and implications for
      electroencephalographic telemetry monitoring and epilepsy surgery.
AB  - Most patients with partial seizures of temporolimbic onset have predominantly
      unilateral seizure foci, which partly accounts for the success of unilateral
      temporal lobectomy. The prevalence of bilateral foci is not known. "Discordant"
      seizures are those which arise from the contralateral side from the usual focus.
      "Concordance" is the fraction of seizures which arise from the majority side,
      ranging from 0.5 to 1.0. From observations of seizures recorded in an epilepsy
      monitoring unit, a model of the patient population can be determined by non
      linear least squares methods. Six hundred and five seizures from 57 consecutive
      patients with non-lesional temporolimbic epilepsy were studied. In the model
      population, 15% of patients have concordance of less than 70%, and 80% have
      concordance > 90%. Using Bayes' theorem, the observation of 5 concordant seizures
      implies a 95% chance of the patient having a concordance of at least 90%. If one
      discordant seizure is recorded, then to reach the 95% confidence level of 90%
      concordance requires a total of 11 concordant seizures. For the smaller group of
      patients with strictly unilateral interictal spikes, only 4 concordant seizures
      need to be recorded to achieve the same level of confidence of unilaterality.
      Interpretation of telemetry studies requires knowledge of the patient population.

PMID- 7525228
TI  - Spatial patterns in the background EEG underlying mental disease in man.
AB  - The spatial patterns underlying differences in the background EEGs of
      schizophrenic, manic and depressed patients and a group of normal controls has
      been examined during the eyes open and eyes closed resting conditions and during
      3 cognitive tasks. The method of principal-component analysis was used to extract
      spatial patterns which are common to the EEGs of 2 groups but which account for
      maximally different proportions of the combined variances. The common spatial
      patterns in all possible pairings of the groups were used to extract variance
      related feature vectors from the individual EEG epochs in the 2 groups and the
      means of these vectors were subjected to statistical analyses. The results of
      these analyses indicate that there are significant differences in the EEGs from
      all 4 of the groups. The spatial patterns underlying the features which are
      significantly different in each comparison are shown graphically and used to
      suggest which brain regions might be implicated in each of the psychiatric
      conditions and how these are affected by the cognitive condition. The main
      results are that the EEGs in the schizophrenic group can be characterized by left
      sided hyperactivity, in the depressed group by right-sided hyperactivity and in
      the manic group by bilateral hyperactivity and that these characteristics are
      best elicited by different cognitive states.

PMID- 7525230
TI  - Fractal analysis of electroencephalographic signals intracerebrally recorded
      during 35 epileptic seizures: evaluation of a new method for synoptic
      visualisation of ictal events.
AB  - Traditional electroencephalography (EEG) produces a large volume display of brain
      electrical activity, which creates problems particularly in assessment of long
      periods of intracranial, stereoelectroencephalographic (SEEG) recording. A method
      for fractal analysis that describes 100 SEEG data points in terms of a single
      estimate of fractal dimension (1 < FD < 2) is reported; the central processing
      unit time costs amount to approximately 2 min/Mbyte of input signal (using a Sun
      SPARCstation LX). The diagnostic sensitivity of this method, applied to
      quantification and synoptic visualisation of SEEG signals recorded during 35
      epileptic seizures in 7 patients, is evaluated. It is found that the method
      consistently defines ictal onset in terms of rapid relative increase in FD across
      several channels. Clinically severe seizures are characterised by more intense
      and generalised ictal changes in FD than clinically less severe events. For all 7
      patients, and for 75% of individual seizures, "fractal diagnoses" of anatomically
      defined ictal onset zone coincided closely with ictal onset zone independently
      determined by inspection of traditional EEG displays of the same data. We
      conclude that the method is a computationally feasible way to achieve substantial
      reduction in the volume of SEEG data without undue loss of diagnostically
      important information in the primary signal.

PMID- 7525232
TI  - Lesions of frontal cortex diminish the auditory mismatch negativity.
AB  - Event-related brain potentials to non-attended auditory stimuli were recorded
      from patients with dorsolateral prefrontal cortex (DPFCx) lesions and from age
      matched control subjects as they performed a visual reaction time task. Auditory
      stimuli consisted of monaural sequences of repetitive standard tones (1000 Hz)
      and occasional deviant tones of a higher frequency (1300 Hz). In comparison with
      control subjects, DPFCx patients showed enhanced P1 amplitudes (mean peak latency
      50 msec), consistent with reduced frontally mediated gating of sensory input to
      the auditory cortex. The mismatch negativity (MMN) elicited by deviant tones was
      reduced in DPFCx patients over a broad latency range (130-210 msec), especially
      over the lesioned hemisphere and for tones delivered to the ear ipsilateral to
      the lesion. The results suggest that DPFCx and DPFCx-temporal projections play a
      critical role in involuntary orienting to physical changes in sequences of non
      attended auditory stimuli.

PMID- 7525233
TI  - Human brain potentials of spatial location encoding into memory.
AB  - Event-related potentials (ERP) were elicited by little vertical bars located
      randomly in 1 of 4 positions (top, bottom, left or right) relative to a central
      fixation point. There were 4 experimental conditions requiring the subjects
      either to press a button if the stimulus was in the target location, count the
      number of stimuli appearing in the target location, look at the stimuli passively
      or memorize the location of the stimulus. The interstimulus interval was 2 sec
      for all tasks. In the memory condition subjects had to consider stimuli as pairs,
      memorize the location of the first stimulus of every pair and press a button if
      the second stimulus was in the same location. Our results indicate that ERPs
      corresponding to the memorization and retention of spatial location are different
      from those of the other 3 tasks in the presence of a long duration negativity
      mainly distributed bilaterally over O1, O2, T5 and T6 electrodes. This negativity
      seems to develop gradually several milliseconds before stimulus onset, reaches
      its highest value when the spatial location is assumed to be analyzed, and
      continues with uniform scalp distribution until the end of the recording (822
      msec after stimulus onset).

PMID- 7525234
TI  - Location of electric current sources in the human brain estimated by the dipole
      tracing method of the scalp-skull-brain (SSB) head model.
AB  - Using a realistic, 3-shell head model including the scalp (S), skull (S) and
      brain (B) with conductivity ratios of 1:1/80:1, respectively, the electrical
      activity in the human brain recorded by conventional electroencephalography was
      approximated by 1 or 2 equivalent current dipoles. The dipole locations and
      vector moments were estimated by minimizing the squared difference between the
      potentials actually recorded from the scalp and those theoretically calculated
      from the equivalent dipoles. The validity of this dipole tracing method (the DT
      of the SSB head model) was tested in patients with focal epileptic seizures
      undergoing presurgical evaluation with intracranial subdural strip electrodes.
      Weak currents were passed through 1 or 2 pairs of subdural electrodes to create
      artificial dipoles. The dipole estimations correctly distinguished between single
      and double generator sources, but there were certain dislocations of the
      calculated dipoles. The average error of dislocation was found to be 8.5 mm for
      the 1-dipole model. That for the 2-dipole model was 6 mm for one of the
      components and 18 mm for the other. It was concluded that the DT method of the
      SSB head model can be a valuable clinical tool in 3-dimensional localization of
      focal epileptic discharges in the human brain.

PMID- 7525236
TI  - Visual and somatosensory evoked potentials are mediated by excitatory amino acid
      receptors in the thalamus.
AB  - In pentobarbital-anaesthetized rats early somatosensory evoked potentials (SEPs)
      were recorded from the sensory cortex in response to electrical stimulation of
      the contralateral forepaw and visual evoked potentials (VEPs) from the primary
      visual cortex in response to single light flashes. Microapplication of the
      specific non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the
      ventro-basal thalamus (VB) resulted in a pronounced decrease in amplitude and an
      increase in latency of SEPs, whereas injection of DNQX into the dorsal lateral
      geniculate nucleus (DGL) induced a pronounced decrease in amplitude and an
      increase in latency of VEPs. These changes were: (1) dose-dependent (DNQX 0.01
      1.0 nmol), (2) receptor-specific, and (3) site-specific. In contrast, the
      specific NMDA antagonist 2-amino-7-phosphonoheptanoate (AP7; 0.5-5 nmol) did not
      affect SEPs after microapplication into the BV and less potently reduced the
      amplitude and increased the latency of VEPs after microapplication into the DGL.
      The present findings are consistent with the assumption that an excitatory amino
      acid serves as transmitter at synapses in the rat thalamus mediating the nervous
      impulses responsible for the generation of SEPs and of VEPs. In addition the
      results suggest that this transmitter preferentially interacts with non-NMDA
      receptors.

PMID- 7525237
TI  - Activation sequence of discrete brain areas during cognitive processes: results
      from magnetic field tomography.
AB  - Magnetic field tomography is a technique for extracting 3-dimensional estimates
      of current density in the brain, from non-contact, non-invasive measurements of
      the magnetic field generated by the brain. It allows visualisation of both
      cortical and subcortical focal activation patterns at millisecond intervals, and
      the relative time difference between active cortical areas. We have used this
      technique to study the activation history of discrete brain regions associated
      with the preparation for, initiation and inhibition of movement, and movement
      itself in a CNV paradigm. The strongest focal activities are found within well
      defined cortical regions, namely the auditory (A1), sensorimotor (SM1), medial
      parietal area (MPA) and anterior supplementary motor area (SMA). For the movement
      condition, activation history differs for the warning stimulus and the stimulus
      initiating movement.

PMID- 7525235
TI  - Non-linear forecasting measurements of multichannel EEG dynamics.
AB  - This work presents a new method for studying the underlying dynamics of
      multichannel EEG on the basis of the mathematical theory of dynamical systems. It
      computes the local loss of predictability and Kolmogorov entropy of the dynamics
      reconstructed from brain electrical activity. This reconstruction uses
      multichannel recordings in order to quantify an equivalent of spatio-temporal
      mapping. Five experimental conditions have been studied: closed eyes at rest,
      closed eyes and counting even numbers, staring at a spotlight, passive and active
      auditive odd-ball tasks. The entropy is positive for all the experimental
      conditions which proves that the underlying EEG dynamics are chaotic. Moreover,
      on the basis of the dynamical signature it is possible to differentiate 3 types
      of EEG activity: the rest closed eyes activity, the task closed eyes activity
      (counting and odd-ball tasks) and the open eyes activity (staring at a
      spotlight). It is inferred that this index could characterize task-related
      changes in brain activity.

PMID- 7525239
TI  - Electromyographic single motor unit potentials after repeated botulinum toxin
      treatments in cervical dystonia.
AB  - Electromyographic (EMG) single motor unit potentials (MUPs) of the sternomastoid
      muscles (STM) were made before and after repeated treatment with botulinum type A
      toxin (Bx) for cervical dystonia. Post-treatment examinations were 6-25 weeks
      after the latest injection, when symptoms and EMG interference pattern had
      recurred and signs of denervation were scarce. Concentric needle EMG records of
      200 motor unit potentials in 10 patients showed reduced durations and areas after
      treatment (P < 0.05). Increased polyphasia or satellite potentials were not
      observed. Macro-EMG records of 110 MUPs in 6 patients showed reduced amplitudes
      and areas in the injected STM when compared to the untreated side (P < 0.05).
      Fibre density was within the same range (1.0-1.2). The results indicate that the
      pattern of the terminal innervation is mainly restored even after repeated Bx
      treatments, but the number or size of active muscle fibres within the motor unit
      is reduced. The clinical relapse could be due to recovery of the original nerve
      terminals, or to nerve sprouts closely imitating the blocked terminal nerve twigs
      or both.

PMID- 7525238
TI  - Serial electroencephalograms in a patient with D-lactic acidosis.
AB  - A patient with previous bowel surgery was followed through the course of her
      recurrent encephalopathy with biochemically demonstrated D-lactic acidosis by
      detailed serial electroencephalography (EEG). Although the EEG changes were
      marked and parallelled the clinical and biochemical abnormalities closely, they
      were essentially non-specific. This diagnosis should be considered in
      encephalopathic patients with a history of bowel disease particularly after
      extensive small bowel resection.

PMID- 7525240
TI  - Sensory neural conduction of median nerve from digits and palm stimulation in
      carpal tunnel syndrome.
AB  - The median sensory nerve conduction between ring finger and wrist is a suitable
      parameter for early detection of carpal tunnel syndrome (CTS), although shorter
      segments of median nerve have also been proposed for the same goal. In order to
      assess the relative diagnostic value of the sensory nerve conduction velocity
      (SNCV) of the third palmar branch versus the SNCV of the second palmar branch,
      generally performed until now, we studied 62 patients with typical signs and
      symptoms of CTS. The following parameters were evaluated by surface recording:
      orthodromic SNCVs in digit-wrist segments for median (index = M2, third = M3 and
      ring = M4 fingers), ulnar (fourth = U4 finger) and radial (thumb = R1) nerves;
      SNCVs in palm-wrist segments by surface bipolar stimulation at each metacarpo
      phalangeal interspace (second = P2 and third = P3 for the median nerve and fourth
      = P4 for the ulnar nerve); and distal motor latencies of the median and ulnar
      nerves. No responses at the wrist were recorded in 22.6% of patients after
      digital stimulation of M4, whereas the SNCV of P3, the palmar nerve branch
      arising from digital nerves of the medial side of M3 and the lateral side of M4,
      was measurable in 93.5% of patients. As significantly expressed (P < 0.001) by
      the increased ratio of the mean values of P2 and P3 in CTS patients, the SNCV of
      P3 decreased more frequently and to a greater extent than the SNCV of P2.

PMID- 7525241
TI  - Quantitative surface EMG of pericranial muscles in headache. A population study.
AB  - Quantitative EMG from the right frontal and both temporal muscles was studied in
      547 adults randomly selected from the general population. The study was part of a
      multifaceted, epidemiological study of different headache disorders. Surface EMG
      was recorded by an observer blinded to the persons' history of headache, previous
      illness and mental state. The present study provides data on amplitude and mean
      and median frequency levels in migraine and tension-type headache. Chronic
      headache sufferers had higher amplitude values at rest in their temporal muscles
      than migraineurs, subjects with episodic tension-type headache and subjects
      without any experience of headache, probably due to insufficient relaxation.
      Frequency values during maximal voluntary contraction were decreased in chronic
      headache subjects and decreased with increasing frequency of headache in the
      previous year, indicating that chronic fatigue and/or changed fiber type
      composition exist in frequent headache sufferers. During experimental cold and
      pain stimulation no significant differences between headache subjects and the
      rest of the population were detected. Only subjects without any experience of
      headache had increased amplitude values during pain stimulation. No significant
      relation of amplitude values to frequency of tension-type headache or migraine in
      the previous year was detected. In 66 subjects with actual headache amplitude
      values were increased in the frontal muscle during rest indicating increased
      tension. Moreover, amplitude values were decreased in both the temporal and the
      frontal muscles during maximal voluntary contraction indicating submaximal
      contraction during pain. The present study supports the importance of peripheral
      factors such as increased fatigability, morphological, and/or metabolic changes
      in the pathogenesis of tension-type headache. However, the diagnostic value of
      EMG in migraine and tension-type headache is limited.

PMID- 7525243
TI  - Evidence for further recruitment of group I fibres with high stimulus intensities
      when using surface electrodes in man.
AB  - Changes in the firing probability of voluntarily activated motor units in the
      human lower limb were recorded in response to stimuli applied to peripheral
      nerves of the lower limb using surface electrodes. In each instance the
      monosynaptic Ia excitation produced by heteronymous afferent volleys was studied.
      This peak of excitation was found to increase with the intensity of the
      stimulation up to 2.5-4 x the motor threshold (MT), i.e., 4-7 x the threshold of
      Ia afferents. It is concluded that, when using surface electrodes in human
      subjects, group Ia effects may not be maximal with stimulus intensities below 4 x
      MT, and the effects evoked by different afferent populations (e.g., Ia and II)
      cannot be clearly separated solely on the basis of the electrical excitability of
      these fibres.

PMID- 7525242
TI  - Muscle sympathetic nerve activity during apneic episodes in patients with
      obstructive sleep apnea syndrome.
AB  - Muscle sympathetic nerve activity (MSNA) was recorded from peroneal nerve in 4
      OSAS patients during sleep. During apneic episode, MSNA was enhanced, but it did
      not increase progressively toward the end of the apneic episode. MSNA remained at
      a stable level in the later part of an apneic episode. A surge of MSNA took place
      just preceding or just at the end of an apneic episode and it was followed by a
      transient marked blood pressure elevation.

PMID- 7525244
TI  - Finding the depth of magnetic brain stimulation: a re-evaluation.
AB  - The depth of threshold magnetic nerve stimulation can be estimated by using
      thresholds from two different-sized stimulus coils and plotting their induced
      electric field vs. depth profiles. Stimulation is presumed to take place where
      the two field profiles are equal. If the two coils have unequal inductances,
      however, there is a relative shift in threshold between coils that alters the
      intersection point and the apparent stimulus depth. This systematic error arises
      from two sources: (1) there is a difference in the fraction of stimulator energy
      reaching each coil, and (2) pulse durations are different, causing threshold
      shifts governed by the nerve strength-duration curve. Both sources of error are
      additive. If the larger coil has the lesser inductance, stimulus depth is
      underestimated; if it has the greater inductance, it is overestimated. This can
      lead to large disparities in the measured depth, depending on the sets of coils
      used. In this paper, we show how to correct for errors introduced by unequal
      inductance and how this resolves discrepancies in depth measurement. Our own
      depth measurements in the motor area for threshold finger movements, and
      recalculated depths from Epstein et al., indicate that stimulation is slightly
      deeper (18-21 mm, average 19+ mm) than previously thought. This suggests that
      threshold magnetic stimulation in the motor area may arise from large,
      tangentially oriented fibers in the superficial white matter, or in the gray
      matter at the upper sulcus or lip of the gyrus.

PMID- 7525246
TI  - Event-related desynchronization and movement-related cortical potentials on the
      ECoG and EEG.
AB  - Event-related desynchronization (ERD) 2.0 sec before and 1.0 sec after movement
      in the frequency bands of 8-10, 10-12, 12-20 and 20-30 Hz and movement-related
      cortical potentials (MRCPs) to self-paced movements were studied from subdural
      recordings over the central region in 3 patients, and from scalp-recorded EEGs in
      20 normal volunteers. In direct cortical recordings, the peak ERD response and
      peak MRCP amplitude to self-paced finger movements were maximal over recording
      sites in the contralateral hand motor representations. The topography and time of
      onset of the ERD response to finger and foot movements suggest that the ERD
      responses in the 8-10 Hz and 10-12 Hz bands are more somatotopically restricted
      than the responses in the higher frequency bands. The power recovery and
      subsequent overshoot in the different frequency bands occurred in an orderly
      fashion with the faster frequencies recovering earlier. The ERD responses on the
      scalp-recorded EEGs were of lower magnitude and more widely distributed than
      those occurring on the subdural recordings. Across the population, there was no
      relation between the magnitude of the ERD response in any of the frequency bands
      studied and the peak amplitude of the negative slope (pNS') and the frontal peak
      of the motor potential (fpMP) of the MRCPs. MRCPs and ERD responses originate in
      similar cortical regions and share some common timing features, but the magnitude
      and spatial distribution of the two responses appear to be independent of each
      other, which suggests that the physiological mechanisms governing these two
      events are different and may represent different aspects of motor cortex
      activation. Differences in the timing and topographical features of the ERD
      responses in the various frequency bands also suggest a distinct functional
      significance for the various spectral components of the electrical activity in
      the motor cortex.

PMID- 7525245
TI  - Reduction of corticospinal excitability by magnetic stimulation over the
      cerebellum in patients with large defects of one cerebellar hemisphere.
AB  - The reduction of motor cortex excitability by magnetic stimulation over the
      lateral basiocciput of normal subjects has up to the present time been attributed
      to an activation of cerebellar structures. This hypothesis was tested in one
      patient with complete agenesis and two patients with extensive infarction of one
      cerebellar hemisphere. Unexpectedly, stimulation over the intact and absent or
      damaged cerebellar hemispheres reduced the susceptibility of the contralateral
      and, to a lesser degree, the ipsilateral motor cortex to cortical magnetic test
      stimuli given 9 msec after the stimulus over the cerebellum. The anatomic
      structure, activated by stimulation over the lateral occiput, remains unclear but
      activation of brain-stem structures, rather than the cerebellum, has been
      postulated. Increased thresholds for the excitation of the hand-associated motor
      cortex contralateral to the cerebellar lesion correlated with slow and clumsy
      finger movements ipsilateral to the cerebellar lesion, which suggests
      facilitatory influences of the cerebellum on the contralateral corticospinal
      system under normal conditions.

PMID- 7525247
TI  - 8-12 Hz rhythmic oscillations in human motor cortex during two-dimensional arm
      movements: evidence for representation of kinematic parameters.
AB  - Direct cortical recordings were taken from 12 patients with implanted subdural
      electrode arrays during performance of a 2-dimensional, multi-joint, visually
      guided arm movement task. Task-related changes in the amplitude of the motor
      cortex 8-12 Hz surface local field oscillations were evaluated for the encoding
      of direction and amplitude of movement in the 6 patients in whom no epileptogenic
      or ECoG background abnormalities were detected over the motor-sensory cortical
      areas under the recording electrode array. The topography, time of onset and
      duration of these responses were evaluated in the context of motor cortex
      somatotopy, as defined by cortical stimulation delivered through the electrode
      array. Multi-joint arm movements were accompanied by a decrease in the power of
      the 8-12 Hz frequency components of the ECoG signal. These power changes were
      spatially distributed over the upper extremity, motor-sensory representation.
      Movement amplitude influenced the magnitude, duration, and extent of the spatial
      distribution of ECoG power changes in the 8-12 Hz band. These effects occurred
      predominantly over cortical areas corresponding to the upper extremity motor
      sensory representations. Direction of movement had a weaker influence on the 8-12
      Hz frequency components of the ECoG over the upper extremity motor-sensory
      representations, but influenced the patterns of 8-12 Hz ECoG response on adjacent
      cortical regions. These results show that the amplitude of surface electrical
      oscillations generated over the rolandic cortex are correlated with the
      kinematics of multi-joint arm movements. These changes in the ECoG signal appear
      to reflect shifts in the functional state of neuronal ensembles involved in the
      initiation and execution of motor tasks.

PMID- 7525248
TI  - Masseter silent period: a study of magnetic stimulation.
AB  - We employed magnetic stimulation to study the masseter silent period (SP) in 16
      healthy volunteers. Cutaneous perception threshold (CPT or 1 T) was determined.
      SP threshold was 30% M (maximal output) in each subject, equivalent to 1.5-3 T,
      and as intensity increased, SP durations prolonged. The correlation was higher
      with units of % M (r = 0.89) than CPT (r = 0.39). The recommended intensity was
      60% M because of least variation of SP durations. Conclusively, magnetic
      stimulation is a new and painless method to study masseter SP. CPT is less
      effective in studying masseter SP with magnetic stimulation as the input
      effectiveness correlates best with % M rather than CPT.

PMID- 7525249
TI  - Once is not enough--promiscuity begets diversity among the insulin-like growth
      factor binding proteins.

PMID- 7525252
TI  - Nitric oxide: an autocrine regulator of human granulosa-luteal cell
      steroidogenesis.
AB  - We investigated the presence of nitric oxide (NO) synthase in ovarian follicular
      cells obtained from women undergoing in vitro fertilization procedures.
      Endothelial NO synthase messenger RNA was demonstrated by polymerase chain
      reaction amplification of reverse transcribed RNA. NO synthase was localized to
      granulosa-luteal cells by immunocytochemistry, using a monoclonal antibody.
      Ovarian follicular cell NO synthase enzyme activity was confirmed by measuring
      the conversion of L-arginine to citrulline. To investigate the effect of NO on
      granulosa-luteal cell steroidogenesis, NO synthase inhibitors and NO donors were
      added to cell cultures. NG-Monomethyl-L-arginine and N-nitro-arginase methyl
      ester, selective inhibitors of NO synthase, significantly increased estradiol
      secretion by granulosa-luteal cells. S-Nitroso-L-acetyl penicillamine (S-NAP) and
      S-nitroso glutathione, NO donors, caused a dose-dependent decrease in both
      estradiol and progesterone secretion. The decrease by S-NAP was reversed by
      hemoglobin, which binds free NO. Although S-NAP increased the concentration of
      cGMP in granulosa-luteal cells, cGMP analogs had no effect on steroidogenesis in
      cell cultures. S-NAP and native NO in solution decreased cellular and microsomal
      aromatase activities. We conclude that NO synthase is present in human granulosa
      luteal cells and that NO inhibits estradiol secretion independent of cGMP by
      directly inhibiting aromatase.

PMID- 7525251
TI  - Insulin-like growth factors cross the blood-brain barrier.
AB  - Although evidence exists that insulin may cross the blood-brain barrier, little
      is known about the ability of insulin-like growth factors (IGF-I and -II) to
      cross this barrier. In the present studies, equimolar concentrations of equal
      specific activity 125I-labeled IGF-I, IGF-II, or insulin were infused into the
      carotid artery of anesthetized adult rats. The perfusions were carried out for 3
      min in the presence or absence of excess unlabeled ligand or insulin, with three
      or more animals in each group. Immediately after the perfusion, brains were
      frozen and sectioned for autoradiography. All ligands were detected in choroid
      plexus, median eminence, and blood vessels, but [125I]IGF-I and -II were also
      prominently localized in brain parenchyma. Densitometric analysis of film
      autoradiographs (28-day exposure for all ligands) revealed that radiolabeled
      IGFs, especially IGF-I, were significantly more abundant throughout the forebrain
      than [125I]insulin, especially in the paraventricular nucleus, where [125I]IGF-I
      was 10-fold and [125I]IGF-II was 5-fold more abundant than [125I]insulin. The
      difference in [125I]IGF-I vs. [125I]insulin accumulation was confirmed by
      parallel measurements of radioactivity in anatomically matched brain sections
      using a gamma-spectrometer. The uptake of radiolabeled IGF-I, IGF-II, and insulin
      by brain parenchyma and vasculature was completely inhibited by excess (1,000
      fold) unlabeled ligand; however, insulin (10,000-fold excess) did not completely
      abolish [125I]IGF-I and -II accumulation. Microscopic evaluation of nuclear
      emulsion-coated brain sections revealed that radioactivity associated with
      [125I]IGF-I and -II perfusions was selectively concentrated in capillaries and
      medium-sized parenchymal cells in the paraventricular nucleus and, to a lesser
      extent, the supraoptic nucleus and anterior nucleus of the thalamus, whereas in
      other brain regions the radioligands were mostly bound to capillaries. These
      results suggest that radiolabeled IGF-I and -II bind to brain capillaries and
      cross the blood-brain barrier into brain parenchyma more readily than
      radiolabeled insulin.

PMID- 7525250
TI  - The regulation of insulin-like growth factor-binding protein 1 messenger
      ribonucleic acid in cultured rat hepatocytes: the roles of glucagon and growth
      hormone.
AB  - In previous studies it was shown that bovine GH (bGH) suppressed and glucagon
      stimulated the level of 24- and 30- to 34-kilodalton insulin-like growth factor
      binding proteins (IGFBPs) in the media of cultured rat hepatocytes. In the
      present study we have evaluated the regulation of IGFBP-1 gene expression in
      primary rat hepatocyte cultures. Glucagon produced a dose-dependent stimulation
      of hepatocyte IGFBP-1 messenger RNA (mRNA), attaining levels 2- to 6-fold greater
      than control at a glucagon concentration of 100 ng/ml. GH inhibited the
      accumulation of IGFBP-1 mRNA in a dose-dependent manner producing, 40-70%
      inhibition at 50 ng/ml. The effect of glucagon was comparable to and additive
      with dexamethasone (1 microM). The addition of 3-isobutyl-1-methylxanthine (100
      microM) and (Bu)2cAMP (100 microM) augmented IGFBP-1 mRNA levels 5- to 6-fold. 4
      beta-Phorbol 12 beta-myristate 13 alpha-acetate (300 nM) was found to inhibit
      IGFBP-1 mRNA levels by 40-50%. The inhibitory effect of bGH on IGFBP-1 mRNA
      levels was abolished after preincubation with 4 beta-phorbol 12 beta-myristate 13
      alpha-acetate (10 microM) for 24 h, whereas glucagon's stimulatory effect was
      unaffected. The addition of staurosporine (500 nM) and H-7 (1 mM) abolished the
      inhibitory effect of GH but also significantly inhibited the stimulatory effect
      of glucagon, a result consistent with these agents acting on both protein kinase
      C (PKC) and PKA. In the presence of 10 micrograms/ml cycloheximide, IGFBP-1 gene
      expression was superinduced by bGH, whereas the effect of glucagon was
      uninfluenced. Thus the inhibitory action of GH involves, in part, the activation
      of PKC. Glucagon's stimulatory effect seems to involve the activation of PKA. The
      inhibitory effect of bGH on IGFBP-1 gene expression may require the continuing
      synthesis of one or more labile protein(s).

PMID- 7525253
TI  - Immunofluorescent localization of thyroid hormone receptor isoforms in glial
      cells of rat brain.
AB  - The three currently recognized T3 binding thyroid hormone receptor (TR) isoforms,
      TR alpha 1, TR beta 1, and TR beta 2, arise from two distinct genes (alpha and
      beta), whereas two closely related non-T3-binding receptor variants, collectively
      designated TR alpha 2, arise from alternate splicing of the alpha gene
      transcript. Using a panel of specific antisera to these isoforms we have assessed
      the presence or absence of TRs in oligodendrocytes and astrocytes of rat cerebrum
      and cerebellum. Inferences as to colocalization of the receptor isoforms and cell
      specific marker proteins were based on immunohistochemical analysis of the
      differential emissions of paired immunofluorescent probes. Antisera against
      myelin basic protein (MBP) identified oligodendroglia, and glial fibrillary
      acidic protein identified astrocytes. MBP-positive oligodendrocytes displayed
      positive fluorescent signals with each of the three TR isoform-specific antisera
      and the antiserum to the receptor variants. These findings are consistent with
      the concept that the MBP gene is a direct target for thyroid hormone action. TR
      immunoreactivity appeared to localize primarily to the nuclei of these cells. In
      contrast, we observed no immunofluorescent signals for any of the TR isoforms in
      glial fibrillary acidic protein-positive astrocytes. These findings raise the
      possibility that any effect of thyroid hormone on astrocyte function and
      structure is mediated indirectly as a result of interaction of thyroid hormone
      with receptors situated in nonastrocyte cells or as a result of nonnuclear
      mechanisms.

PMID- 7525254
TI  - Effects of parathyroid hormone on cytosolic calcium of rat adipocytes.
AB  - Available data indicate that adipocytes are targets for PTH action, and chronic
      excess of PTH increases calcium burden of fat tissue, suggesting that PTH
      increases entry of calcium into adipocytes. The present study examined the
      effects of PTH-(1-84) and its amino-terminal fragment, PTH-(1-34), on cytosolic
      calcium ([Ca2+]i) of adipocytes and evaluated the cellular pathways that mediate
      the potential effect of PTH on [Ca2+]i of these cells. PTH-(1-84) but not PTH-(1
      34) produced a dose-dependent rise in [Ca2+]i of adipocytes. This effect occurred
      in the presence or absence of calcium in the media, but the magnitude of the rise
      in [Ca2+]i was significantly greater when calcium was present in the media. The
      PTH antagonist [Nle8,18Tyr34]bPTH(7-34)NH2, verapamil, and nifedipine blocked to
      variable degrees the PTH-induced rise in [Ca2+]i. The phorbol ester 12-O
      tetradecanoyl phorbol-13-acetate, and the GTP-binding protein (G protein) GTP
      gamma S also produced a dose-dependent rise in [Ca2+]i of adipocytes. These
      effects were inhibited by staurosporine and the G protein inhibitor guanosine 5'
      O-1(2-thiodiphosphate), respectively. Similary, staurosporine, calphostin C,
      guanosine 5'-O-1(2-thiodiphosphate), and pertussis toxin inhibited the effect of
      PTH on [Ca2+]i of adipocytes. (Bu)2cAMP also increased [Ca2+]i of adipocytes, but
      PTH did not stimulate cAMP production by adipocytes, and N-[2(p-bromocin
      namylamino)ethyl]5-isoquinoline-sulfonamide, an inhibitor of protein kinase A,
      did not affect the PTH-induced rise in [Ca2+]i of adipocytes. The data indicate
      that: 1) PTH-(1-84) increases [Ca2+]i of adipocytes; 2) this action of the
      hormone is receptor mediated; 3) the hormone uses a G protein activation of
      calcium channels and the phospholipase C pathway in mediating its action on
      [Ca2+]i; and 4) the rise in [Ca2+]i is due to both increased calcium influx into
      the adipocytes and mobilization of calcium from intracellular stores.

PMID- 7525255
TI  - Gonadotropin suppression of apoptosis in cultured preovulatory follicles:
      mediatory role of endogenous insulin-like growth factor I.
AB  - Although the majority of ovarian follicles undergo atresia through a mechanism
      involving apoptotic cell death, in vivo studies concerning the hormonal
      regulation of atresia have been difficult due to the presence of heterogeneous
      population of follicles in the ovary. In the present study, the regulation of
      follicle apoptosis by gonadotropins, insulin-like growth factor I (IGF-I), and
      IGF-binding protein 3 (IGFBP-3) was examined using a serum-free culture of
      preovulatory follicles. Immature rats at 26 days of age received a single dose of
      PMSG. Two days later, the largest preovulatory follicles were collected for in
      vitro culture with or without hormones. After 24 h of culture, follicular
      apoptotic DNA fragmentation was analyzed by autoradiography of size-fractionated
      DNA labeled at 3'-ends by [32P]dideoxy-ATP. A spontaneous increase in apoptotic
      DNA fragmentation occurred after 24 h of culture in the absence of hormones,
      whereas treatment with human CG (hCG) or FSH suppressed follicular apoptosis in a
      dose-dependent manner, with 0.1 microgram/ml causing maximal suppression by 60
      62%. Cotreatment with hCG and FSH had no additional effect. Like gonadotropins,
      treatment with IGF-I and insulin also suppressed the spontaneous onset of
      apoptosis, with IGF-I being more effective than insulin. Cotreatment with IGFBP-3
      and hCG dose-dependently reversed the suppressive effect of hCG on apoptosis by
      42%, suggesting a mediatory role of endogenously produced IGF-I. The addition of
      IGFBP-3 also blocked the suppressive action of IGF-I by 49%, whereas it did not
      affect the suppressive action of an IGF-I agonist or insulin. Treatment with
      IGFBP-3 alone had no effect on apoptotic DNA fragmentation. Estrogen and
      progesterone production by the cultured follicles were also analyzed by RIA.
      Gonadotropin treatment resulted in a marked stimulation of the production of both
      steroid productions. In contrast, treatment with IGF-I caused a small increase in
      estrogen but decreased progesterone production. Although treatment with IGFBP-3
      alone decreased both estrogen and progesterone production, cotreatment with IGFBP
      3 and hCG resulted in a slight decrease in estrogen production but an increase in
      progesterone production. Furthermore, IGFBP-3 did not affect IGF-I action on
      steroid production. To further substantiate the hypothesis that IGFBP-3 blocks
      the suppressive effect of hCG on apoptosis by neutralizing endogenously produced
      IGF-I, solution hybridization analysis was performed, and hCG treatment was shown
      to increase IGF-I messenger RNA levels in cultured follicles by 1.9
      fold.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525257
TI  - Consequences of postnatally elevated insulin-like growth factor-II in transgenic
      mice: endocrine changes and effects on body and organ growth.
AB  - Insulin-like growth factor-II (IGF-II) is an important regulator of embryonic
      growth and differentiation, but its function in postnatal life is unclear. To
      address this point, we generated transgenic mice harboring fusion genes in which
      a human IGF-II complementary DNA is placed under the transcriptional control of
      the rat phosphoenolpyruvate carboxykinase promoter. Transgene-specific messenger
      RNA was detected in liver, kidney, and several parts of the gut. Serum IGF-II
      levels in transgenic mice were 2-3 times higher than those in controls and
      increased after starvation. Circulating IGF-I correlated negatively and IGF
      binding protein-2 (IGFBP-2) positively with IGF-II levels, suggesting that IGF-I
      is displaced from IGFBPs by IGF-II and that IGF-II is a major regulator of IGFBP
      2. Serum levels of IGFBP-3 and IGFBP-4 tended to be higher in phosphoenolpyruvate
      carboxykinase-IGF-II transgenic mice than in controls, as evaluated by ligand
      blot analysis. Starvation reduced serum IGF-I, but increased IGFBP-2 in
      transgenic mice more markedly than in controls. Fasting insulin levels were
      significantly reduced in transgenic mice, whereas glucose levels were not
      influenced by elevated IGF-II. The body growth of 4- and 12-week-old mice was not
      significantly influenced by elevated IGF-II, but transgenic mice displayed
      increased kidney and testis weight at the age of 4 weeks, and increased adrenal
      weight at the age of 12 weeks. Our results demonstrate that elevated IGF-II in
      postnatal life has multiple endocrine consequences and subtle time-specific
      effects on organ growth.

PMID- 7525256
TI  - Expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins
      during adipogenesis.
AB  - Insulin-like growth factor-I (IGF-I) stimulates the differentiation of
      preadipocytes, but the expression of IGF-I and IGF-binding proteins (IGFBPs)
      during the course of adipogenesis has not been investigated. Using two in vitro
      models, primary mouse preadipocytes and the 3T3-L1 preadipocyte cell line
      stimulated to differentiate with IGF-I, we studied IGF and IGFBP expression
      before and during differentiation. Primary preadipocyte cultures expressed IGF-I,
      IGFBP-2, and IGFBP-4 messenger RNAs (mRNAs), and conditioned medium (CM)
      contained IGFBP-3 [approximately 46,000 mol wt (M(r))], IGFBP-4 (24,000 M(r)),
      and a 30,000 M(r) IGFBP identified by immunoblot as IGFBP-2. During
      differentiation, an additional approximately 34,000 M(r) form of IGFBP-2 was
      predominant, but IGFBP-2 mRNA decreased, suggesting that a mechanism other than
      steady state mRNA levels is regulating protein abundance in CM. Like primary
      cultures, undifferentiated 3T3-L1 cells expressed IGFBP-4 mRNA, but insignificant
      levels of IGF-I and IGFBP-2 mRNAs. 3T3-L1 cell CM contained IGFBP-3 and IGFBP-4,
      and with the addition of IGF-I, a 30,000 M(r) IGFBP was also present. This IGFBP
      was not recognized by antiserum to IGFBP-1, -2, -4, -5, or -6. During
      differentiation of 3T3-L1 cells, an approximately 34,000 M(r) form of IGFBP-2 was
      also present in CM. In summary, primary cultures of mouse preadipocytes and 3T3
      L1 cells express similar IGFBPs during IGF-I-stimulated adipogenesis. The
      presence of a larger isoform of IGFBP-2 in a differentiation-dependent manner and
      a potentially novel IGFBP in response to IGF-I suggests that these IGFBPs may be
      important in modulating IGF-I action in adipogenesis.

PMID- 7525258
TI  - Recombinant human insulin-like growth factor (IGF)-binding protein-1 inhibits
      somatic growth stimulated by IGF-I and growth hormone in hypophysectomized rats.
AB  - We have examined the effects of exogenously administered recombinant human
      insulin-like growth factor-binding protein-1 (rhIGFBP-1) alone and in combination
      with recombinant human insulin-like growth factor-I (rhIGF-I) or human GH on
      weight gain and tibial epiphysis enlargement in hypophysectomized rats. rhIGF-I,
      given twice daily by sc injection, increased both growth parameters in a dose
      dependent manner. Coadministration of increasing amounts of rhIGFBP-1 with a
      constant amount of rhIGF-I (80 micrograms/injection, given twice daily) resulted
      in a dose-dependent inhibition of the growth-promoting effects of rhIGF-I. A
      rhIGFBP-1 dose of 9.8 micrograms/injection (an IGFBP-1/IGF-I molar ratio of
      0.04:1) caused no significant effect on rhIGF-I-stimulated growth parameters,
      whereas a rhIGFBP-1 dose of 1200 micrograms/injection (IGFBP-1/IGF-I molar ratio
      of 5:1) resulted in 78% or greater inhibition of rhIGF-I-stimulated growth (P <
      0.05). rhIGFBP-1 doses of 48 and 240 micrograms/injection (IGFBP-1/IGF-I molar
      ratios of 0.2:1 and 1:1, respectively) had intermediate inhibitory effects. None
      of the rhIGFBP-1 doses potentiated the growth-promoting effects of rhIGF-I. Rats
      treated with rhIGFBP-1 alone (twice daily injections of 9.8, 48, 240, or 1200
      micrograms) showed no significant differences in growth parameters compared to
      rats treated with vehicle. Coadministration of rhIGFBP-1 (1200
      micrograms/injection, given twice daily) with GH (15 mU/injection, given twice
      daily) inhibited weight gain and tibial epiphysis enlargement stimulated by GH by
      at least 50% in each of two experiments (P < 0.05). These studies demonstrate
      that nonphosphorylated rhIGFBP-1 can inhibit the growth-promoting effects of
      rhIGF-I and GH in vivo. The results suggest that in addition to its proposed role
      in glucose homeostasis, IGFBP-1 may play a role in inhibiting somatic growth and
      other physiological functions stimulated by IGF-I and GH.

PMID- 7525259
TI  - Insulin-like growth factor-binding protein-2 and -3 are correlated with atresia
      and preovulatory maturation in the porcine ovary.
AB  - We compared insulin-like growth factor-binding protein (IGFBP) levels with
      indicators of follicular maturation and atresia in individual follicles of the
      porcine ovary. Follicular development was synchronized with the progestin,
      altrenogest, and progestin withdrawal was used to initiate the growth of an
      ovulatory cohort of follicles, which is accompanied by atresia of noncohort
      follicles. Individual follicles were isolated on days 1, 3, 5, and 7 after
      progestin withdrawal. Atretic follicles were identified by the presence of low
      hypodiploid levels of DNA in 10% or more of their granulosa cells using flow
      cytometry. The follicular fluid (FF) level of IGFBP-3 did not differ
      significantly between healthy and atretic medium-sized (3- to 6-mm) follicles and
      was not significantly correlated with the percentage of granulosa cells
      containing hypodiploid levels of DNA (r = 0.181) or with endocrine parameters
      such as FF concentrations of estradiol or androstenedione. However, among healthy
      follicles (atretic follicles removed from analyses to better examine follicular
      maturation), IGFBP-3 increased (P < 0.01) between days 1 and 7 and was positively
      correlated with follicle diameter (r = 0.514; P < 0.05) and the FF concentration
      of progesterone (r = 0.556; P < 0.01), indicators of the degree of follicular
      maturation. FF IGFBP-2 levels were 3-fold greater (P < 0.01) in atretic than in
      healthy follicles, and IGFBP-2 was correlated with percentage of granulosa cells
      containing hypodiploid levels of DNA (r = 0.729; P < 0.001). Among healthy
      follicles, FF IGFBP-2 did not differ significantly among days and was not
      significantly correlated with follicle diameter. These data suggest that the
      content of IGFBP-2 is related to the state of follicular health/atresia, whereas
      IGFBP-3 is related to preovulatory follicular development.

PMID- 7525260
TI  - Detection of a kallikrein in the mouse lactating mammary gland: a possible
      processing enzyme for the epidermal growth factor precursor.
AB  - Kallikreins are a multigene subfamily of serine proteases that may have a role in
      processing precursors of polypeptide hormones and growth factors. The epidermal
      growth factor (EGF) immunoreactivity in mouse milk is derived from the membrane
      bound EGF precursor located on the lumenal border of the alveolar cells in the
      mammary gland. Release of EGF into the milk requires the hydrolysis of the EGF
      precursor at Arg-X cleavage sites. We report the presence of a candidate EGF
      precursor-processing enzyme in the lactating mouse mammary gland. Kallikrein
      transcripts in the mouse lactating mammary gland were detected by primer-directed
      enzyme amplification of complementary DNA (cDNA). Primers to selected conserved
      regions of the kallikrein cDNA resulted in an amplified product of the predicted
      size (573 basepairs). Sequence analysis of the product over three nonconserved
      regions identified mGK-6 (mouse renal kallikrein) as the primary kallikrein in
      BALB/c mouse lactating mammary gland. Transcription products for the EGF-binding
      protein (mGK-9), mGK-1, MGK-3, and mGK-4 were not detected by enzyme
      amplification with specific primers corresponding to these kallikrein cDNAs.
      Positive immunohistochemical staining of the apical membrane of mammary alveolar
      cells was detected with a polyclonal antiserum to mouse kallikrein. Incubation of
      cell membranes isolated from lactating mammary glands released soluble EGF
      immunoreactive material. Aprotinin partially inhibited the release of this
      material, whereas other protease inhibitors, such as leupeptin, benzamidine, and
      limabean trypsin inhibitor, had no detectable effect. These results support the
      hypothesis that the release of EGF-immunoreactive material into the milk is in
      part dependent upon a kallikrein enzyme (mGK-6) in the BALB/c mouse lactating
      mammary gland.

PMID- 7525262
TI  - Parathyroid hormone (PTH) and PTH-related peptide induce relaxation of smooth
      muscle cells from guinea pig ileum: interaction with vasoactive intestinal
      peptide receptors.
AB  - PTH-related peptide (PTHrP), which shares 8 of 13 NH2-terminal residues with PTH,
      causes similar biological effects and interacts with the same receptor as PTH. In
      the gastrointestinal tract, human PTH and PTHrP-(1-34) relax rat fundic strips.
      However, the level of their action and the receptor involved in this effect are
      unknown. The aims of this study were 1) to determine the effects of human PTH-(1
      34), human PTHrP-(1-34), -(1-16), and -(7-34) and vasoactive intestinal peptide
      (VIP) on circular isolated smooth muscle cells from guinea pig ileum; 2) to study
      the intracellular pathways involved in these effects; and 3) and to characterize
      the receptors involved by using specific antagonists. Smooth muscle cells were
      dispersed by enzymatic digestion. Contraction was assessed by measuring the
      length of 50 cells and expressed as the percent decrease in cell length from the
      control value. The relaxing effects of PTH, PTHrP and analogs, VIP, or
      antagonists were expressed as a percentage of the maximal effect observed in
      their absence. VIP, PTH-(1-34), and PTHrP-(1-34), -(1-16), and -(7-34) had no
      effect by themselves on these cells. However, when cells were contracted by the
      sulfated C-terminal octapeptide of cholecystokinin (10 nM), VIP, PTH-(1-34), and
      PTHrP(1-34) inhibited the sulfated C-terminal octapeptide of cholecystokinin
      induced contraction in a concentration-dependent manner, whereas PTHrP-(1-16) and
      -(7-34) had no effect. The EC50 values of VIP, PTH-(1-34), and PTH-(1-34), and
      PTHrP-(1-34) were 7 nM, 20 pM, and 20 pM, respectively. The VIP antagonist ([D-P
      Cl-Phe6,Leu17]VIP) inhibited VIP-, PTH-(1-34)-, and PTHrP(1-34)-induced
      relaxation, with IC50 values of 20, 500, and 400 pM, respectively. Likewise, the
      PTH/PTHrP antagonist [Tyr34-bovine PTH-(7-34)NH2] inhibited PTH-(1-34)-, PTHrP(1
      34)-, and VIP-induced relaxation, with IC50 values of 1, 1, and 90 pM,
      respectively. Preincubation of cells with somatostatin, N-ethylmaleimide, and (R)
      p-cyclic adenosine-3',5'-monophosphothioate inhibited the PTH-(1-34), PTHrP(1-34)
      , and VIP-induced relaxation. In conclusion, human PTH and PTHrP induce a
      relaxation of intestinal smooth muscle by a direct myogenic effect. This effect
      requires the 1-34 amino acid sequence and is mediated by the activation of
      adenylate cyclase and protein kinase-A. Interactions among PTH, PTHrP, and VIP
      indicate that they may cross-react with their respective receptors.

PMID- 7525261
TI  - Secretogogue-induced gating of chloride channels in the secretory vesicles of
      parafollicular cells.
AB  - Thyroid parafollicular (PF) cells are neural crest-derived endocrine cells that
      secrete serotonin and calcitonin. The secretory vesicles of PF cells acidify when
      secretion is induced by increased extracellular Ca2+ or TSH. We tested the
      hypothesis that acidification is regulated by secretogogue-gated Cl- channels in
      vesicular membranes. Cl- channel (p64) immunoreactivity was enriched in purified
      PF vesicles. X-Ray microanalysis showed a change in chlorine level in PF vesicles
      in response to secretogogue-stimulation of isolated cells. Secretogogue
      stimulation also altered the degree of p64 channel phosphorylation. Protein
      kinase and phosphatase inhibitors antagonized secretogogue-induced vesicle
      acidification and secretion; however, secretion could occur even when
      acidification was blocked. We conclude that acidification of PF vesicles is
      regulated by a gatable Cl- channel in vesicle membranes and that protein
      phosphorylation and dephosphorylation are involved in channel activation.
      Acidification of vesicles is not required for exocytosis.

PMID- 7525264
TI  - Coordinated pattern of expression and localization of insulin-like growth factor
      II (IGF-II) and IGF-binding protein-2 in the adult rat brain.
AB  - Insulin-like growth factors (IGFs) have numerous actions on neuronal and glial
      cell function in vitro, although their in vivo roles within the central nervous
      system (CNS) remain undefined. Levels of IGF-II are high in most rat tissues
      before the third postnatal week, but rapidly decrease thereafter, except in the
      brain and spinal cord, where elevated titers are present in the adult. This
      suggests a function of IGF-II within the CNS. IGF-binding proteins (IGFBPs)
      modify the type 1 IGF receptor-mediated activity of IGFs, thereby regulating the
      activities of IGF-II in the CNS. In this study, we use a ribonuclease protection
      assay, in situ hybridization, and immunohistochemistry to demonstrate that IGF-II
      and one of the major CNS binding proteins, IGFBP-2, show a striking congruency in
      their anatomical pattern of expression and localization throughout the adult rat
      brain. Both proteins are synthesized predominantly in the leptomeninges, choroid
      plexus, and parenchymal microvasculature, but become localized, remote from the
      site of synthesis, in the myelin sheaths of individual myelinated axons and in
      all of the myelinated nerve tracts in the brain, which presumably represents the
      site of IGF-II bioactivity. The spatial disparity between sites of synthesis and
      sites of bioactivity suggests a key role for IGFBP-2 in the regulation of IGF-II
      bioavailability within the brain.

PMID- 7525263
TI  - Recombinant human insulin-like growth factor (IGF)-binding protein-6 inhibits IGF
      II-induced differentiation of L6A1 myoblasts.
AB  - Insulin-like growth factor-binding protein-6 (IGFBP-6) is an O-linked
      glycoprotein that binds insulin-like growth factor-II (IGF-II) with marked
      preferential affinity over IGF-I. Recombinant human IGFBP-6 (rhIGFBP-6) was
      synthesized by COS-7 monkey kidney cells that were transiently transfected with a
      eukaryotic expression vector into which a complementary DNA for IGFBP-6 modified
      for optimal translation had been inserted. rhIGFBP-6 was similar to IGFBP-6
      purified from human cerebrospinal fluid with respect to IGF binding and O
      glycosylation. The effect of rhIGFBP-6 on IGF-induced L6A1 myoblast
      differentiation was studied using creatine kinase activity as an index of
      differentiation. rhIGFBP-6 inhibited differentiation initiated by IGF-II in a
      dose-dependent manner, inhibition was complete when rhIGFBP-6 was present in a
      slight molar excess. In contrast, rhIGFBP-6 had no effect on IGF-I-induced
      differentiation, even when coincubated in a 5-fold molar excess. These results
      are consistent with the preferential affinity of IGFBP-6 for IGF-II. As cell
      association and proteolysis have been associated with the potentiation, rather
      than the inhibition, of IGF action by IGFBPs, we investigated whether they
      occurred in the L6A1 myoblast system. After incubation of L6A1 myoblasts with
      rhIGFBP-6, IGFBP-6 was recovered from the medium, but not from cell lysates or
      extracellular matrix. In addition, [125I]IGFBP-6 did not bind to myoblast
      monolayers, and there was no evidence that proteolysis had occurred. Together,
      these results indicate that rhIGFBP-6 remains intact and soluble and, hence,
      inhibits IGF-II-induced differentiation. The fidelity of the IGFBP-6 expression
      system used for these studies will enable us to use this system to determine how
      structural modifications of the protein affect the modulation of IGF action by
      IGFBP-6.

PMID- 7525265
TI  - The involvement of nitric oxide in the ovulatory process in the rat.
AB  - Nitric Oxide (NO) is now recognized as a mediator of several biological
      functions. In the present study we examined the effects of NO synthase (NOS)
      inhibitors on the ovulatory process in vivo, and whether this effect can be
      reversed by a NO generator. Immature eCG-hCG treated rats were injected
      intraperitonealy (ip) or unilaterally into the periovarian sac (intrabursal
      injection; ib) with inhibitors of the inducible form of NOS. Aminoguanidine (AG)
      suppressed ovulation in a dose-dependent manner, reaching a 54% inhibition at a
      dose of 20 mg/kg when injected ip (p < 0.001 vs. saline control). Likewise, local
      ib administration inhibited ovulation from the treated ovary; thus a dose of 2
      mg/kg resulted in 48% inhibition, as compared to the contralateral ovary (p <
      0.01). Similar results were obtained whether AG was administered 2 h prior to the
      stimulation of ovulation by hCG or deferred up to 4 h afterwards. An additional
      NOS inhibitor, NG-methyl-L-arginine (L-NMA) suppressed ovulation, albeit to a
      lower extent. Intrabursal administration of L-NMA (0.1 and 1 mg/kg) resulted in
      34% and 32% inhibition, respectively (p < 0.05 vs. the saline treated control).
      The same doses of NG-methyl-D-arginine (D-NMA) did not inhibit ovulation
      significantly compared to the saline treated control. When sodium nitroprusside
      (0.5 mg/kg), a NO generator, was injected concomitantly with AG, it completely
      reversed its inhibitory action on ovulation. Thus, we have demonstrated the
      ability of NOS inhibitors to suppress hCG-induced ovulation in the rat in vivo.
      The specificity of this effect is confirmed by the ability of a NO generator to
      reverse the inhibitory action of AG. In conclusion, the ovarian NO/NOS system
      seems to be necessary for follicle rupture during ovulation.

PMID- 7525267
TI  - Temperature dependence of multiple high voltage activated Ca2+ channels in chick
      sensory neurones.
AB  - The temperature dependence of high voltage activated Ca2+ channels has been
      investigated in cultured dorsal root ganglion neurones from chick embryos, using
      the cell-attached patch-clamp technique. The dihydropyridine sensitive L-type
      Ca2+ channel had a conductance of 23 pS, with 110 mM Ba2+ as charge carrier and
      in the presence of 3 microM Bay K 8644. When the temperature was raised from 15
      to 30 degrees C, the unitary channel current amplitude increased, with Q10 value
      equal to 1.4. The rising phase of the averaged single-channel current became
      faster, with Q10 value 2.7, whereas the decay phase showed a lower temperature
      sensitivity. Channel open probability decreased according to an exponential
      distribution of open and closed times. A second type of Ca2+ channel was
      identified, which was DHP-insensitive and had a lower conductance with a mean
      value equal to 13 pS. For the current amplitude, the Q10 value was 1.3. Both
      activation and inactivation kinetics were strongly accelerated by an increase in
      temperature. The corresponding time constants gave Q10 values equal to 5.9 for
      activation, and 2.0 for inactivation. Peak channel open probability was highly
      sensitive to a change in temperature, with a Q10 value of 1.6. Finally, in omega
      conotoxin GVIA pre-treated neurones, a non-inactivating DHP-insensitive Ca2+
      channel with the lowest unitary conductance (10 pS) and a much lower temperature
      dependence was recorded. Single-channel current was increased by heating, with
      Q10 value 1.3, whereas the channel kinetics were almost unaffected by
      temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525266
TI  - Effects of polycations on ion channels formed by neutral and negatively charged
      alamethicins.
AB  - The effects of the peptide polycations salmon protamine (M(r) = 4332, z = +21)
      and poly-L-lysine (M(r) approximately equal to 100,000, z approximately equal to
      +775) on ion channels formed by synthetic alamethicin Alm-F30 (one negative
      charge), natural Alm-F50 (neutral) and phosphorylated Alm-F50 (two negative
      charges) reconstituted in planar lipid bilayers have been studied at the single
      channel level. It was observed that both polycations in micromolar concentrations
      transiently block ion permeation through the channels formed by each alamethicin
      analogue, although in case of the neutral Alm-F50 to a significantly lesser
      extent. Poly-L-lysine showed to be more effective than protamine in blocking
      these channels. If either polycation is present in the cis-compartment, blockade
      occurs only at cis positive membrane voltages. At constant polycation
      concentration, dwell times in the blocked state increase when salt concentration
      is lowered, and decrease at acidic pH with an apparent pK of 4.8. Mean lifetime
      of blockade events shortens when membrane voltage is increased, which suggests
      that both polycations may permeate through the oligomeric alamethicin channels if
      conductance levels are > 2. We suggest that blockade is caused by electrostatic
      binding of a single polycation molecule to the C-terminal channel mouth; in case
      of Alm-F30, Glu18 has to be considered as the putative binding site. Our results
      provide further evidence for the barrel-stave model and a parallel orientation of
      dipole monomers in the channel aggregate, the C-termini facing the membrane side
      with the more positive membrane potential.

PMID- 7525268
TI  - Association of the amino-terminal half of c-Src with focal adhesions alters their
      properties and is regulated by phosphorylation of tyrosine 527.
AB  - We have characterized the mechanism by which the subcellular distribution of c
      Src is controlled by the phosphorylation of tyrosine 527. Mutation of this
      tyrosine dramatically redistributes c-Src from endosomal membranes to focal
      adhesions. Redistribution to focal adhesions occurs independently of kinase
      activity and cellular transformation. In cells lacking the regulatory kinase
      (CSK) that phosphorylates tyrosine 527, c-Src is also found predominantly in
      focal adhesions, confirming that phosphorylation of tyrosine 527 affects the
      location of c-Src inside the cell. The first 251 amino acids of c-Src are
      sufficient to allow association with focal adhesions, indicating that at least
      one signal for positioning c-Src in focal adhesions resides in the amino-terminal
      half. Point mutations and deletions in the first 251 amino acids of c-Src reveal
      that association with focal adhesions requires the myristylation site needed for
      membrane attachment, as well as the SH3 domain. Expression of the amino-terminal
      region alters both the structural and biochemical properties of focal adhesions.
      Focal adhesions containing this non-catalytic portion of c-Src are larger and
      exhibit increased levels of phosphotyrosine staining. Our results suggest that c
      Src may regulate focal adhesions and cellular adhesion by a kinase-independent
      mechanism.

PMID- 7525269
TI  - Structural organization of the pentameric transmembrane alpha-helices of
      phospholamban, a cardiac ion channel.
AB  - Phospholamban is a 52 amino acid calcium regulatory protein found as pentamers in
      cardiac SR membranes. The pentamers form through interactions between its
      transmembrane domains, and are stable in SDS. We have employed a saturation
      mutagenesis approach to study the detailed interactions between the transmembrane
      segments, using a chimeric protein construct in which staphylococcal nuclease (a
      monomeric soluble protein) is fused to the N-terminus of phospholamban. The
      chimera forms pentamers observable in SDS-PAGE, allowing the effects of mutations
      upon the oligomeric association to be determined by electrophoresis. The
      disruptive effects of amino acid substitutions in the transmembrane domain were
      classified as sensitive, moderately sensitive or insensitive. Residues of the
      same class lined up on faces of a 3.5 amino acids/turn helical projection,
      allowing the construction of a model of the interacting surfaces in which the
      helices are associated in a left-handed pentameric coiled-coil configuration.
      Molecular modeling simulations (to be described elsewhere in detail) confirm that
      the helices readily form a left-handed coiled-coil helical bundle and have
      yielded molecular models for the interacting surfaces, the best of which is
      identical to that predicted by the mutagenesis. Residues lining the pore show
      considerable structural sensitivity to mutation, indicating that care must be
      taken in interpreting the results of mutagenesis studies of channels. The
      cylindrical ion pore (minimal diameter of 2 A) appears to be defined largely by
      hydrophobic residues (I40, L43 and I47) with only two mildly polar elements
      contributed by sulfurs in residues C36 and M50.

PMID- 7525270
TI  - Contribution of structural elements to Thermus thermophilus ribonuclease P RNA
      function.
AB  - We have performed a deletion and mutational analysis of the catalytic
      ribonuclease (RNase) P RNA subunit from the extreme thermophilic eubacterium
      Thermus thermophilus HB8. Catalytic activity was reduced 600-fold when the
      terminal helix, connecting the 5' and 3' ends of the molecule, was destroyed by
      deleting 15 nucleotides from the 3' end. In comparison, the removal of a large
      portion (94 nucleotides, about one quarter of the RNA) of the upper loop region
      impaired function only to a relatively moderate extent (400-fold reduction in
      activity). The terminal helix appears to be crucial for the proper folding of
      RNase P RNA, possibly by orientating the adjacent universally conserved
      pseudoknot structure. The region containing the lower half of the pseudoknot
      structure was shown to be a key element for enzyme function, as was the region of
      nucleotides 328-335. Deleting a conserved hairpin (nucleotides 304-327) adjacent
      to this region and replacing the hairpin by a tetranucleotide sequence or a
      single cytidine reduced catalytic activity only 6-fold, whereas a simultaneous
      mutation of the five highly conserved nucleotides in the region of nucleotides
      328-335 reduced catalytic activity by > 10(5)-fold. The two strictly conserved
      adenines 244 and 245 (nucleotides 248/249 in Escherichia coli RNase P RNA) were
      not as essential for enzyme function as suggested by previous data. However,
      additional disruption of two helical segments (nucleotides 235-242) adjacent to
      nucleotides 244 and 245 reduced activity by > 10(4)-fold, supporting the notion
      that nucleotides in this region are also part of the active core
      structure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525271
TI  - Base pairing between Escherichia coli RNase P RNA and its substrate.
AB  - Base pairing between the substrate and the ribozyme has previously been shown to
      be essential for catalytic activity of most ribozymes, but not for RNase P RNA.
      By using compensatory mutations we have demonstrated the importance of Watson
      Crick complementarity between two well-conserved residues in Escherichia coli
      RNase P RNA (M1 RNA), G292 and G293, and two residues in the substrate, +74C and
      +75C (the first and second C residues in CCA). We suggest that these nucleotides
      base pair (G292/+75C and G293/+74C) in the ribozyme-substrate complex and as a
      consequence the amino acid acceptor stem of the precursor is partly unfolded.
      Thus, a function of M1 RNA is to anchor the substrate through this base pairing,
      thereby exposing the cleavage site such that cleavage is accomplished at the
      correct position. Our data also suggest possible base pairing between U294 in M1
      RNA and the discriminator base at position +73 of the precursor. Our findings are
      also discussed in terms of evolution.

PMID- 7525273
TI  - Homing of a group II intron in yeast mitochondrial DNA is accompanied by
      unidirectional co-conversion of upstream-located markers.
AB  - Group II introns ai1 and ai2 of the Saccharomyces cerevisiae mitochondrial COXI
      gene encode proteins having a dual function (maturase and reverse transcriptase)
      and are mobile genetic elements. By construction of adequate donor genomes, we
      demonstrate that each of them is self-sufficient and practises homing in the
      absence of homing-type endonucleases encoded by either group I introns or the
      ENS2 gene. Each of the S. cerevisiae group II self-mobile introns was tested for
      its ability to invade mitochondrial DNA (mtDNA) from two related Saccharomyces
      species. Surprisingly, only ai2 was observed to integrate into both genomes. The
      non-mobility of ai1 was clearly correlated with some polymorphic changes
      occurring in sequences flanking its insertion sites in the recipient mtDNAs.
      Importantly, studies of the behaviour of these introns in interspecific crosses
      demonstrate that flanking marker co-conversion accompanying group II intron
      homing is unidirectional and efficient only in the 3' to 5' direction towards the
      upstream exon. Thus, the polar co-conversion and dependence of the splicing
      proficiency of the intron reported previously by us are hallmarks of group II
      intron homing, which significantly distinguish it from the strictly DNA-based
      group I intron homing and strictly RNA-based group II intron transposition.

PMID- 7525272
TI  - The structural and functional basis for the kirromycin resistance of mutant EF-Tu
      species in Escherichia coli.
AB  - A structural and functional understanding of resistance to the antibiotic
      kirromycin in Escherichia coli has been sought in order to shed new light on the
      functioning of the bacterial elongation factor Tu (EF-Tu), in particular its
      ability to act as a molecular switch. The mutant EF-Tu species G316D, A375T,
      A375V and Q124K, isolated by M13mp phage-mediated targeted mutagenesis, were
      studied. In this order the mutant EF-Tu species showed increasing resistance to
      the antibiotic as measured by poly(U)-directed poly(Phe) synthesis and intrinsic
      GTPase activities. The K'd values for kirromycin binding to mutant EF-Tu.GTP and
      EF-Tu.GDP increased in the same order. All mutation sites cluster in the
      interface of domains 1 and 3 of EF-Tu.GTP, not in that of EF-Tu.GDP. Evidence is
      presented that kirromycin binds to this interface of wild-type EF-Tu.GTP, thereby
      jamming the conformational switch of EF-Tu upon GTP hydrolysis. We conclude that
      the mutations result in two separate mechanisms of resistance to kirromycin. The
      first inhibits access of the antibiotic to its binding site on EF-Tu.GTP. A
      second mechanism exists on the ribosome, when mutant EF-Tu species release
      kirromycin and polypeptide chain elongation continues.

PMID- 7525274
TI  - Decay-accelerating factor CD55 is identified as the receptor for echovirus 7
      using CELICS, a rapid immuno-focal cloning method.
AB  - Using an anti-receptor mAb that blocks the attachment of echovirus 7 and related
      viruses (echoviruses 13, 21, 29 and 33), we have isolated a complementary DNA
      clone that encodes the human decay-accelerating factor (CD55). Mouse cells
      transfected with the CD55 clone bind echovirus 7, and this binding is blocked by
      the anti-receptor mAb. The method used (CELICS) allows rapid and direct cloning
      of genes encoding cell surface receptors. It is based on episomal replication and
      high efficiency expression of complementary DNA clones in the vector pCDM8 in COS
      or WOP cells, in conjunction with a sensitive immuno-focal screen that uses
      antibody probes linked to beta-galactosidase. Receptor positive cells were
      identified by a colour change and isolated individually using a micromanipulator.
      DNA extracted from a small number of cells was then cloned directly in
      Escherichia coli.

PMID- 7525278
TI  - Bacterial mutagenicity, metabolism, and DNA adduct formation by binary mixtures
      of benzo[a]pyrene and 1-nitropyrene.
AB  - Air pollutants are a complex mixture containing polycyclic organic compounds.
      Among these are 1-NP and B[a]P, which are important contributors to the
      mutagenicity of diesel exhaust and airborne particulate matters. To investigate
      the interaction of a complex mixture of airborne mutagens, the mutagenicity of 1
      NP was examined with S. typhimurium TA98 and TA98NR in the presence and absence
      of B[aP. B[a]P exhibited a more antagonistic effect on the mutagenicity of 1-NP
      in strain TA98 than in strain TA98NR. Also studied were (1) the inhibitory
      effects of B[a]P on the nitroreductive metabolism of 1-NP and (2) DNA adduct
      formation by 1-NP. Nitroreductase was associated with the metabolism of 1-NP, and
      was reduced in a dose-dependent manner in a binary mixture of 1-NP and B[a]P.
      HPLC analysis showed that the amounts of 1-AP and NAAP, the metabolites of 1-NP,
      were significantly decreased by the addition of B[a]P in mixtures. The results
      indicate that the antagonistic effect of B[a]P on the mutagenicity of 1-NP is
      mediated through altering its nitroreductive metabolism.

PMID- 7525277
TI  - Evidence that SCEs induced by mutagens do not occur at the same locus in
      successive cell cycles: lack of cancellation in three-way stained CHO
      chromosomes.
AB  - An approach based on the synchronization of CHO cells after a first cell cycle
      incorporating a relatively low amount of bromodeoxyuridine (BrdUrd) into DNA,
      followed by mutagenic treatment and subsequent culture for second and third
      generations of BrdUrd incorporation for the scoring of sister chromatid exchanges
      (SCEs) per cell cycle in three-way differentially (TWD) stained chromosomes, has
      been used to investigate the possible cancellation of SCEs. Cancellation is
      expected to occur if two mutagen-induced SCEs occur at exactly the same site in
      subsequent rounds of replication. Lesions in DNA seem to persist and are able to
      induce SCE throughout two cell cycles after treatment with the three mutagens
      tested--mitomycin C (MMC), ethyl methanesulfonate (EMS) and ultraviolet (UV)
      light--though this latter agent was shown as only moderately persistent. Our
      results seem to indicate that SCEs induced by these mutagens do not take place at
      the same locus in successive cell generations, as assessed by a lack of SCE
      cancellation.

PMID- 7525279
TI  - The value of sputum gram stain in the diagnosis of pneumococcal pneumonia.
AB  - The utility of sputum Gram stain in identifying Gram positive diplococci and
      other bacteria was studied in 39 patients with community acquired pneumonia
      (CAP). The results of the Gram stain of the sputum were compared to the Gram
      stain of the lung aspirate (LA). Of 28 patients whose LA smear showed Gram
      positive diplococci, 26 (95%) had the same organisms, either exclusively or
      predominantly, in their sputum. One patient had Gram negative rods both in the
      sputum and lung aspirate. Seventy-one per cent of patients with positive LA stain
      versus 50% with negative LA stain had taken antimicrobials for less than 36 hours
      prior to coming to hospital. We conclude that sputum Gram stain is a sensitive
      method for the diagnosis of pneumococcal pneumonia and is unaffected by a short
      period of prior antimicrobial treatment.

PMID- 7525275
TI  - Novel pattern of editing regions in mitochondrial transcripts of the cryptobiid
      Trypanoplasma borreli.
AB  - In mitochondria of Kinetoplastida belonging to the suborder Trypanosomatina, the
      nucleotide sequence of transcripts is post-transcriptionally edited via insertion
      and deletion of uridylate residues. In order to shed more light on the
      evolutionary history of this process we have searched for editing in
      mitochondrial RNAs of Trypanoplasma borreli, an organism belonging to the
      suborder Bodonina. We have cloned and sequenced a 5.3 kb fragment derived from a
      37 kb mitochondrial DNA molecule which does not appear to be a part of a network
      structure and have found genes encoding cytochrome c oxidase (cox) subunit 1, cox
      2 and apocytochrome (cyt) b, and genes encoding the small and large subunit
      mitoribosomal RNAs. The order in which these genes occur is completely different
      from that of trypanosomatid maxicircle genes. The 5' and 3' termini of both the
      cytb and cox1 gene are cryptic, the protein coding sequences being created by
      extensive insertion/deletion of Us in the corresponding mRNA sections.
      Phylogenetic analyses of the protein and ribosomal RNA sequences demonstrated
      that the separation between T.borreli and Trypanosomatina was an early event,
      implying that U-insertion/deletion processes are ancient. Different patterns of
      editing have persisted in different lineages, however, since editing of cox1 RNA
      and of relatively small 3'-terminal RNA sections is not found in trypanosomatids.
      In contrast, cox2 RNA which is edited in trypanosomatids by the insertion of four
      Us, is unedited in T.borreli.

PMID- 7525276
TI  - Escherichia coli PriA protein is essential for inducible and constitutive stable
      DNA replication.
AB  - Under certain conditions, Escherichia coli cells exhibit either of two altered
      modes of chromosomal DNA replication. These are inducible stable DNA replication
      (iSDR), seen in SOS-induced cells, and constitutive stable DNA replication
      (cSDR), seen in rnhA mutants. Both iSDR and cSDR can continue to occur in the
      absence of protein synthesis. They are dependent on RecA protein, but do not
      require DnaA protein or the oriC site. Here we report the requirement for PriA, a
      protein essential for assembly of the phi X174-type primosome, for both iSDR and
      cSDR. In priA1(Null)::kan mutant cells, iSDR is not observed after induction by
      thymine starvation. Replication from one of the origins (oriM1) specific to iSDR
      is greatly reduced by the priA1::kan mutation. cSDR in rnhA224 mutant cells
      deficient in RNase HI is also completely abolished by the same priA mutation. In
      both cases, SDR is restored by introduction of a plasmid carrying a wild-type
      priA gene. Furthermore, the viability of an rnhA::cat dnaA46 strain is lost at 42
      degrees C upon inactivation of the priA gene, indicating the lethal effect of
      priA inactivation on those cells whose viability depends on cSDR. These results
      demonstrate that a function of PriA protein is essential for iSDR and cSDR and
      suggest the involvement of the PriA-dependent phi X174-type primosome in these
      DnaA/oriC-independent pathways of chromosome replication. Whereas ColE1-type
      plasmids, known to be independent of DnaA, absolutely require PriA function for
      replication, DnaA-dependent plasmid replicons such as pSC101, F, R6K, Rts1 and
      RK2 are able to transform and to be maintained in the priA1::kan strain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7525280
TI  - Proteasome-associated RNAs are non-specific.
AB  - The RNA isolated from RNase-treated proteasome preparations from human
      erythrocytes, HeLa cells, the archaeon Thermoplasma acidophilum and also from
      recombinant proteasomes of T. acidophilum expressed in Escherichia coli was
      characterized. The RNA associated with structurally similar protein particles,
      namely with the two molecular chaperones, groEL from E. coli and with the
      thermosome from T. acidophilum, served as controls. Electrophoretic analysis on
      polyacrylamide gels of the radioactively end-labelled RNA revealed a very similar
      size distribution pattern, irrespectively of the protein particles from which
      they had been isolated. The predominant RNA species were in the size ranges 80
      nucleotides and 120 nucleotides, respectively. Partial sequencing of their
      terminal regions by mobility-shift analysis revealed that, of the proteasomes
      from human erythrocytes, the approximately 80-nucleotide-long RNA consists of a
      heterogenous population of mostly tRNA species because they carried the tRNA
      specific 3'-terminal sequence motif 5'-CCA-3'. The RNA in the size range 120
      nucleotides isolated from the proteasomes of human erythrocytes and of T.
      acidophilum was also heterogeneous and displayed, in the terminal regions, a
      remarkable sequence similarity to the corresponding regions of the 5S rRNA from
      the same and different organisms. The total content of RNA of all the protein
      particles was quantified and found to be consistently sub-stoichiometric. All
      these findings strongly suggest that RNA associated with the proteasomes and with
      the molecular chaperones originate from the abundant cellular pool of the tRNAs
      and 5S rRNAs which bind non-specifically to these large protein particles.

PMID- 7525282
TI  - Enzymology of FK-506 biosynthesis. Purification and characterization of 31-O
      desmethylFK-506 O:methyltransferase from Streptomyces sp. MA6858.
AB  - FK-506 is a macrolide antibiotic with immunosuppressant activity. Structurally,
      this compound contains three methylated hydroxyl groups at C13, C15 and C31.
      Previous biosynthetic studies using stable isotope-feeding experiments have
      established methionine as the source of the methyl for these methylated hydroxyl
      groups. Based on this information and also the availability of the 31-O
      desmethylFK-506, a metabolic precursor for the biosynthesis of FK-506, a S
      adenosyl-L-methionine-dependent enzyme assay was developed and the enzyme 31-O
      desmethylFK-506 O:methyl-transferase was isolated from an extract of Streptomyces
      sp. MA 6858 and purified to near homogeneity. 31-O-DesmethylFK-506
      O:methyltransferase is a monomeric protein with an apparent molecular mass of
      30,000 Da and a pI of 4.4. The first 38 N-terminal amino acids have been
      sequenced and are H2N-SDVVETLRLPNGATVAHVNAGEAQFLYREIFTDRXYLRH. Functionally, This
      enzyme has a requirement for Mg2+ with an optimum temperature of 34 degrees C and
      a pH of 7.4 for full activity. Moreover, it catalyses the methylation of 31-O
      desmethylimmunomycin as efficiently as its own natural substrate, 31-O
      desmethylFK-506. Additionally, FKMT catalyzes the C31 transmethylation reaction
      of 13,31-O-bis-desmethyl-, 15,31-O-bisdesmethyl-, 13,15,31-O-trisdesmethyl- and
      31-O-19,22-cyclic-hemiketalimmunomycins, which are all structural analogues of FK
      506. The reaction is, however, completely blocked if the vicinal hydroxyl which
      is present at the C-32 position of the 31-O-desmethylFK-506 structure is replaced
      with azide, phosphate or other substituents. Finally, evidence is presented
      indicating the close similarity of FKMT and DIMT, a 31-O-desmethyl-immunomycin: O
      methyltransferase, previously isolated from a cell-free extract of Streptomyces
      hygroscopicus var ascomyceticus, an immunomycin (ascomycin/FK-520) producer.

PMID- 7525284
TI  - Isolation and structural analysis of oligosaccharide phosphates containing the
      complete carbohydrate chain of the lipopolysaccharide from Vibrio cholerae strain
      H11 (non-O1).
AB  - For the first time, an oligosaccharide has been prepared comprising the lipid A
      backbone, the core oligosaccharide and one repeating unit of the O-specific
      polysaccharide (O-chain) of a lipopolysaccharide. Lipopolysaccharide from Vibrio
      cholerae strain H11 (non-O1) was deacylated and the products were separated by
      high-performance anion-exchange chromatography. Major fractions were a
      hexadecasaccharide trisphosphate 1, representing the core-lipid A oligosaccharide
      substituted by one modified repeating unit of the O-antigenic polysaccharide, a
      dodecasaccharide trisphosphate 2 and an undecasaccharide trisphosphate 3,
      representing the core-lipid A region. Oligosaccharide 1 originated from beta
      elimination upon alkaline hydrolysis of alpha-galacturonic acid of the O-chain;
      oligosaccharides 2 and 3 were most likely obtained from naturally occurring
      lipopolysaccharide species carrying no O-chain. The structures of these compounds
      were elucidated on the basis of monosaccharide composition, and NMR
      investigations comprising correlation spectroscopy, total correlation
      spectroscopy and nuclear Overhauser enhancement spectroscopy experiments, as well
      as heteronuclear 13C, 1H correlation spectroscopy. The structures are as follows:
      [formula: see text] where R is beta-L-threo-hex-4-enuronopyranosyl-(1-4)-alpha
      Neu-(2-3)-beta-Gal A-(1-3)- beta-QuiN-(1-4)-beta-Sedf-(2- in 1, beta-Sedf-(2- in
      2, and H in 3. Where not stated otherwise, sugars are pyranoses of the D-series.
      Hep is L-glycero-D-manno-heptose, QuiN is 2-amino-2,6-dideoxy-glucose, Kdo is 3
      deoxy-D-manno-2-octulosonic acid, Sed is D-altro-heptulose and GalA is
      galacturonic acid.

PMID- 7525285
TI  - Epidermal-growth-factor-dependent activation of the src-family kinases.
AB  - The precise role of src-type kinases as signal transducers has been under
      intensive investigation but only in a few instances has their role been revealed
      in any detail. Thus, src, fyn and yes are activated upon stimulation by platelet
      derived growth factor or colony-stimulating factor in cells expressing high
      levels of these receptors. Activation of src-family kinases by other receptor
      tyrosine kinases such as the epidermal-growth-factor (EGF) receptor has not been
      directly demonstrated. In this report, we demonstrate EGF-dependent activation of
      src-family tyrosine kinases in NIH3T3 cells overexpressing the human EGF
      receptor. Activation is rapid (< 1 min) and persistent (up to 16 h). Furthermore,
      we show a correlation between the level of EGF receptor expressed and the degree
      of src-family kinase activation. We show that src-family kinase activity is also
      activated by addition of EGF to PC12 cells, which endogenously express relatively
      high levels of EGF receptor. Most strikingly, we show that A431 cells, which
      endogenously express very high levels of EGF receptor, show 10-fold elevated src
      family kinase activity as compared to DHER14 cells, and that this activity is
      constitutive. This activity is completely blocked by AG1478, a specific inhibitor
      of the EGF-receptor tyrosine kinase activity, pointing to a direct link between
      overexpression of the EGF receptor and enhanced src-family kinase activity. Our
      findings suggest that EGF-dependent src-family kinase activity is detectable only
      when the levels of EGF receptor reach a specific level. Additionally, high levels
      of EGF receptor, as in A431 cells, may contribute to the elevated activation of
      src-family kinases. Sustained src-family kinase activation, similar to that seen
      in v-src-transformed cells, may play a role in tumorogenesis and tumor
      maintenance.

PMID- 7525286
TI  - Structure of the Escherichia coli O24 and O56 O-specific sialic-acid-containing
      polysaccharides and linkage of these structures to the core region in
      lipopolysaccharides.
AB  - The lipopolysaccharides from Escherichia coli O24 and O56 could be separated into
      higher-molecular-mass and lower-molecular-mass fractions. Mild acid hydrolysis of
      lipopolysaccharides of both serotypes released an O-specific polysaccharide and a
      tetrasaccharide repeating unit. Oligomers of the repeating unit, the core and the
      oligosaccharide that contains a fragment of the repeating unit linked to the core
      region were also obtained according to hydrolysis conditions. On the basis of
      sugar and methylation analyses, Smith degradation, fast-atom-bombardment mass
      spectrometry and NMR spectroscopy of the hydrolysis products, the biological
      repeating units of the O-specific polysaccharides were shown to be the following
      tetrasaccharides: [formula: see text] The structures differ from the structures
      proposed previously by Kogan et al. [Kogan, G., Shashkov, A. S., Jann, B. & Jann,
      K. (1993) Carbohydr. Res. 238, 261-270; Kogan, G., Jann, B. & Jann, K. (1993)
      Carbohydr. Res. 238, 335-338]. The O-specific repeating unit in E. coli O24
      lipopolysaccharide is linked to O6 of the terminal D-galactose in the core
      region, whereas in O56 LPS the repeating unit is linked to O4 of a subterminal D
      glucose residue in an R2 type core.

PMID- 7525283
TI  - Dissociation of pigeon-liver malic enzyme in reverse micelles.
AB  - Pigeon-liver malic enzyme has a tendency to aggregate at a large concentration of
      protein. The larger aggregates (hexamer and octamer) were demonstrated to be
      enzymically active with specific activity similar to that of the tetramer. When
      the enzyme was embedded in a reverse micellar system prepared by dissolving the
      surfactant sodium bis(2-ethylhexyl)-sulfosuccinate (AOT) in isooctane, the
      tetrameric enzyme dissociated into monomers. The dissociated monomers were also
      enzymically active but with diminished specific activity relative to the activity
      in aqueous media. The decreased enzyme activity in reverse micelles was due to
      interactions of surfactant with the enzyme molecules, suggesting that the
      cytosolic malic enzyme is located near the plasma membrane. When the dissociation
      was monitored by altering the degree of hydration of the system (represented by
      the ratio [H2O]/[AOT]), the detergent and organic solvent slightly affected KTD,
      the dissociation constant of tetramer to dimers (T <--> 2 D), but increased KDM,
      the dissociation constant of dimer to monomers (D <--> 2 M), by 1-2 orders of
      magnitude; this change caused a 2-3 orders of magnitude increase in the overall
      dissociation constant KTM (T <--> 4 M). The dissociation of the tetrameric malic
      enzyme to monomers was favored by approximately 16 kJ/mol in AOT/isooctane
      reverse micelles versus aqueous media. We propose water-shell and induced-fit
      models for the enzyme in AOT/isooctane reverse micelles at large and small
      [H2O]/[AOT] ratios to explain this data, respectively. The asymmetric quaternary
      structure of the enzyme [Lee, H. J. & Chang, G. G. (1990) FEBS Lett. 277, 175
      179] was re-evaluated in terms of the subunit interactions and various
      interconvertible enzyme forms.

PMID- 7525287
TI  - Binding of purified collagen receptors (alpha 1 beta 1, alpha 2 beta 1) and RGD
      dependent integrins to laminins and laminin fragments.
AB  - Integrins alpha 1 beta 1 and alpha 2 beta 1 when purified by collagen affinity
      chromatography, showed distinct binding to mouse tumor laminin-1, which has the
      chain composition alpha 1 beta 1 gamma 1. The binding was, however, about 10-fold
      lower than to collagen IV. Only little (alpha 1 beta 1) or no binding (alpha 2
      beta 1) was observed to two different laminin isoforms (alpha 2 beta 1 gamma 1,
      alpha 2 beta 2 gamma 1) from human placenta. Binding to laminin-1 was abolished
      by EDTA and could be specifically inhibited by antibodies to the respective
      integrin alpha subunit. These antibodies also inhibited cell adhesion to
      collagens. The binding of soluble integrins was weaker than that of immobilized
      integrins but could be enhanced by an activating anti(beta 1 integrin). No
      enhancement was observed for immobilized integrins. Studies with laminin-1
      fragments demonstrated lack of binding to the major cell-adhesive fragment E8
      from the long arm, fragments E3 and E4, involved in heparin-binding and self
      assembly, respectively, and fragment P1, corresponding to the inner segments of
      the short arms. A larger short-arm fragment (E1XNd), which lacks the N-terminal
      beta 1 chain domains V and VI, was as active as laminin. Together, these results,
      suggested the localization of the binding sites for alpha 1 beta 1 and alpha 2
      beta 1 to the N-terminal region of the laminin alpha 1 chain. Fragment P1 but not
      intact laminin-1 bound to alpha V beta 3 integrin in an EDTA-sensitive and RGD
      sensitive manner, underscoring previous data on the cryptic nature of the RGD
      site in laminin-1. Further analyses by surface plasmon resonance assays
      demonstrated a KD = 50 nM for alpha 2 beta 1/laminin-1 binding and a KD = 450 nM
      for alpha V beta 3/fragment P1 binding and confirmed the anti-beta 1-mediated
      increase in affinity for alpha 2 beta 1.

PMID- 7525288
TI  - Posttranslational processing of human alpha 2-HS glycoprotein (human fetuin).
      Evidence for the production of a phosphorylated single-chain form by hepatoma
      cells.
AB  - alpha 2-HS glycoprotein (alpha 2-HS) is a major protein occurring in human blood
      and calciferous tissues. Due to extensive sequence identity, alpha 2-HS has been
      grouped with the fetuins, a family of proteins that occur in fetal plasma in high
      concentrations. Native alpha 2-HS undergoes a series of posttranslational
      modifications including proteolytic processing, multiple N-glycosylations and O
      glycosylations, and sulfation of the carbohydrate side chains. Various two-chain
      forms of alpha 2-HS have been prepared from human plasma, however, the single
      chain precursor has not yet been isolated. Here, we have studied the biosynthesis
      of alpha 2-HS by a human hepatoma cell line, HepG2. We demonstrate that a single
      chain form and the two-chain form of alpha 2-HS are secreted by this cell line.
      The alpha 2-HS forms are further modified by phosphorylation on multiple serine
      residues. Mapping studies indicate that the connecting peptide region releasable
      from the heavy chain of alpha 2-HS contains at least one such phosphorylation
      site. Our results identify proteolytic trimming and/or phosphorylation as
      modifications possibly regulating the biological effects of alpha 2-HS and the
      homologous fetuins.

PMID- 7525281
TI  - Recombinant expression and properties of the Kunitz-type protease-inhibitor
      module from human type VI collagen alpha 3(VI) chain.
AB  - The Kunitz-type inhibitor motif (domain C5) present at the C-terminus of the
      human collagen alpha 3(VI) chain was prepared in a recombinant form from the
      culture medium of stably transfected kidney cell clones. The 76-residue protein
      was disulfide bonded and showed a high stability against protease treatment. The
      recombinant protein lacked, however, any inhibitory activity for trypsin,
      thrombin, kallikrein and several other proteases, which could be due to a few
      unusual substitutions in the region crucial for inhibitor binding. A sensitive
      radioimmunoassay detected low concentrations of C5 epitopes in normal human serum
      and fibroblast culture medium and showed a lack of cross-reaction with aprotinin.
      Antibodies against C5 immunoprecipitated collagen VI obtained from fibroblast
      medium. The C5 epitopes could not be detected on intact collagen VI purified from
      guanidine extracts of human placenta. Collagen VI was shown to possess several
      alpha 3(VI) chain bands (approximately 200 kDa) and reacted strongly with
      antibodies to an N-terminal recombinant fragment. Immunofluorescence with anti-C5
      antibodies failed to stain several human tissues but produced a distinct
      intracellular staining of cultured fibroblasts. The data indicate the rapid loss
      of the C5 domain after biosynthesis of collagen VI.

PMID- 7525289
TI  - Dynamics and pharmacological perturbations of the endoplasmic reticulum in the
      unicellular green alga Acetabularia.
AB  - The giant unicellular green alga Acetabularia was labeled with the lipophilic
      fluorochrome DiOC6 (3,3'-dihexyloxacarbocyanine) and examined by confocal laser
      scanning microscopy to study the distribution of the endoplasmic reticulum (ER)
      and its dynamic changes after the application of inhibitors. In control cells, a
      two-dimensional polygonal network of ER sheets and tubulus is suspended between
      parallel, longitudinally oriented bands. These bands coincide with the main
      physical tracks of organelle transport. All treatments that inhibited organelle
      motility caused a transformation of the polygonal network into confluent large
      patches of lamellar ER sheets. The shape of the lamellar sheets and residual
      activities of the ER were dependent on the inhibitors used. The largest ER
      lamellae were obtained after cytochalasin D (CD) treatment which effectively
      stopped cytoplasmic streaming. CD also caused the formation of a network of fine
      tubules overlapping with the lamellar sheets. Okadaic acid, a specific inhibitor
      of serine/threonine-protein phosphatases, also caused inhibition of organelle
      movement and enlargement of lamellar areas. Tension in the cytoplasm appeared to
      be reduced, as judged from the convexly curved lamellar rims and wavy connecting
      ER tubules. In contrast, N-ethylmaleimide, a sulfhydryl group blocking reagent,
      rapidly stopped streaming and halted all activities of the ER in a rigor-like
      state. These effects are interpreted in the context of actin-based motility
      phenomena prevalent in Acetabularia, and regulatory principles are discussed that
      might underlie ER dynamics.

PMID- 7525291
TI  - The large C-terminal region of the integral pore membrane protein, POM121, is
      facing the nuclear pore complex.
AB  - POM121 is an integral membrane protein that has been specifically localized to
      the "pore membrane" domain of the nuclear envelope. Based on its cDNA-deduced
      primary structure it was suggested that POM121 contains one or two transmembrane
      segments and that its major C-terminal portion faces the pore side rather than
      the cisternal side of the pore membrane. We have investigated the membrane
      topology of POM121 by studying the accessibility of a C-terminal and an N
      terminal epitope of POM121 for epitope-specific antibodies. The accessibility of
      POM121 in unfixed, semi-intact or permeabilized tissue culture cells was analyzed
      by indirect immunofluorescence. We found that the C-terminal epitope was
      accessible for antibodies in both semi-intact and permeabilized cells, whereas
      the N-terminal epitope was only accessible in the permeabilized cells. The
      results show that the large C-terminal region of POM121, containing more than 90%
      of its total mass, is exposed on the pore side of the nuclear membrane and
      suggest that the N-terminal portion is most likely localized in the perinuclear
      space. The data also show that at least part of the C-terminal epitopes are
      localized on the cytoplasmic side of the nuclear envelope. The topology suggests
      that the C-terminal portion of POM121, which contains a nucleoporin-like domain,
      interacts with the nuclear pore complex and thus, may play a role in biogenesis
      of the nuclear envelope and the nuclear pore complex.

PMID- 7525290
TI  - Phosphorylation of microtubule-associated proteins MAP2a,b and MAP2c at Ser136 by
      proline-directed kinases in vivo and in vitro.
AB  - The microtubule-associated protein 2 (MAP2) and its juvenile splicing variant
      MAP2c contain a phosphorylation site at Ser136 which is part of a Ser-Pro motif.
      This site lies within the N-terminal region common to MAP2b and MAP2c. It has
      been mapped by site-directed mutagenesis of recombinant MAP2c and by a monoclonal
      antibody AP18 whose epitope contains the phosphorylated Ser136. In vitro this
      site is phosphorylated by proline-directed kinases such as MAP kinase, GSK-3, or
      members of the cdk family, but not by other kinases such as PKA, PKC, or CaMK-II.
      MAP2a,b or MAP2c isolated from brain is found to be endogenously phosphorylated
      at Ser136. After microinjection into several cell lines dephosphorylated MAP2
      isoforms or recombinant MAP2c become also phosphorylated at Ser136 in vivo.
      Injection of MAP2a,b or MAP2c into living cells causes reorganization of
      microtubules, including bundle formation. This effect is independent of the
      phosphorylation at Ser136. The specificity of the phosphorylation reaction
      provides a tool for analyzing the role and posttranslational processing of MAP2
      in nerve cell development.

PMID- 7525293
TI  - Role of human chorionic gonadotropin in patients with pure seminoma.
AB  - Human chorionic gonadotropin (beta-hCG) and alpha-fetoprotein (AFP) are widely
      established specific and sensitive tumor markers for nonseminomatous testicular
      cancer. In 106 patients with pure seminoma, a highly sensitive method detected
      beta-hCG both before and repeatedly during therapy. The low detection limit of
      the test (0.3 IU/l) coincided with the 95 percentile of a group of 60 healthy
      blood donors. Its 100 percentile of < 1.0 IU/l was applied as the upper limit of
      the normal range. In 30.2% of our patients with pure seminoma, elevated beta-hCG
      levels were noted prior to orchiectomy. The levels returned to normal in 76% of
      these patients thereafter, and in 34% after additional irradiation or
      chemotherapy. During an observation period of 2-84 months, all beta-hCG-positive
      patients were in complete remission. Prior to semicastration, 1 patient showed
      extremely high beta-hCG levels, while in another patient, beta-hCG and AFP were
      elevated simultaneously. In both cases, tumor marker levels did not seem to agree
      with the histology of 'pure seminoma' and rather suggested the presence of
      nonseminomatous tumor cells. Increased AFP levels contradict the presence of a
      pure seminoma and indicate a nonseminomatous testicular tumor. The same holds
      true for strongly elevated beta-hCG levels, whereas levels of up to 200 IU/l
      correlate with the diagnosis of pure seminoma.

PMID- 7525292
TI  - Expression of AgNORs in serous ovarian tumors.
AB  - The nosological nature of the borderline ovarian tumor has been investigated by
      several methodological approaches. The aim of our research was to verify how the
      study of the nucleolar organizer regions (AgNOR) may offer its contribution on
      this subject. We studied 18 cases of ovarian serous tumours, respectively 6
      benign, 6 borderline and 6 malignant. A separate calculation for clusters (> 1
      mu) and total NORs was performed on fifty neoplastic cells chosen at random from
      every tumour. The findings recorded were the following: 1) the quantity and shape
      of clusters, dots and total NORs were significantly increasing from benign to
      borderline to malignant tumours; 2) the number of the dots and total NORs was
      higher in the case of borderline tumour stage III than in other cases limited to
      the ovary; 3) the clusters of the poorly differentiated carcinomas were much less
      numerous than the clusters of those well differentiated; instead the dots and the
      total NORs were more numerous. These data suggest a correlation between the
      number of the NORs and the biological activity of the tumours. The borderline
      serous tumours of the ovary showed a median position between benign and malignant
      tumours.

PMID- 7525294
TI  - Proliferating cell nuclear antigen in needle biopsy specimens of prostatic
      carcinoma.
AB  - The expression of proliferating cell nuclear antigen (PCNA) was
      immunohistochemically determined using a monoclonal antibody PC10 in 54 prostatic
      carcinoma samples. The samples were taken from needle biopsy specimens which had
      been paraffin-embedded after routine fixation with 10% formaldehyde solution
      (formalin) for less than 24 h. The PCNA index was calculated as the percentage of
      positive tumor cell nuclei. There was a significant difference in the PCNA index
      according to the growth pattern (p < 0.001), nuclear anaplasia (p < 0.001) and T
      stage (p < 0.01). Regarding the growth pattern, solid carcinomas showed a
      significantly higher PCNA index than did either separate gland carcinomas (p <
      0.05) or trabecular/fused gland carcinomas (p < 0.05). The PCNA index correlated
      closely with either the nuclear anaplasia or T stage, and increased in
      conjunction with the increased nuclear anaplasia (rs = 0.641; p < 0.001) or T
      stage (rs = 0.435; p < 0.01). The patients in the high PCNA index (> or = 15%)
      group showed a significantly worse survival than did those in the lower PCNA
      index group (p < 0.01), and multivariate analyses indicated that the PCNA index
      had an independent prognostic significance. These results suggest that the PCNA
      index, as determined by PC 10 on needle biopsy specimens of prostatic carcinoma,
      can thus be an objective and quantitative means for evaluating the biological
      malignancy of prostatic carcinoma.

PMID- 7525295
TI  - Regulation of ICAM-3 (CD50) membrane expression on human neutrophils through a
      proteolytic shedding mechanism.
AB  - The regulation of the cell surface expression of ICAM-3 (CD50) was investigated
      in human neutrophils. Immunofluorescence flow cytometry analysis revealed a
      remarkable and very rapid down-regulation of the ICAM-3 cell surface expression
      upon neutrophil activation with stimulating agents such as phorbol myristate
      acetate (PMA) or calcium ionophore. A similar low expression of ICAM-3 was
      observed on neutrophils from patients undergoing hemodialysis with cell
      activating cellulosic membranes. Internalization assays with 125I-labeled anti
      ICAM-3 monoclonal antibody (mAb) suggested that ICAM-3-down-regulation was due to
      antigen release from the cell surface towards the outer milieu, rather than to
      antigen internalization. Immunoprecipitation studies confirmed this down
      regulatory effect, and revealed the presence of ICAM-3 in cell-free supernatants
      from activated neutrophils. Furthermore, the presence of a soluble form of ICAM-3
      with a range of concentrations of 0-296 ng/ml in the plasma from healthy human
      volunteers was detected by using a two-site mAb radioimmunoassay. A proteolytic
      mechanism likely accounts for this process since protease inhibitors virtually
      abrogated the PMA-induced down-regulation of ICAM-3. Functional studies showed
      that anti-ICAM-3 mAb were able to trigger homotypic neutrophil aggregation both
      before and after ICAM-3 down-regulation, indicating that the fraction of ICAM-3
      molecules remaining on the neutrophil surface upon activation are still capable
      of sustaining cell adhesion. In contrast, the loss of L-selectin (CD62L) on
      activated neutrophils was almost complete, thus leading to an impairment of L
      selectin-mediated neutrophil-endothelial cell adhesion. These results indicate
      that ICAM-3 is released to the medium upon neutrophil stimulation and that both
      ICAM-3 and L-selectin have a role in the neutrophil adhesive phenomena.

PMID- 7525297
TI  - Macrophage-T cell interaction in experimental mycobacterial infection. Selective
      regulation of co-stimulatory molecules on Mycobacterium-infected macrophages and
      its implication in the suppression of cell-mediated immune response.
AB  - The most important immunopathological consequence of experimental mycobacterial
      infection is the suppression of T cell-mediated immune response to both mitogens
      and mycobacterial antigens. We registered that there was decreased concanavalin A
      induced spleen cell proliferation in infected susceptible BALB/c mice as compared
      to normal mice. In resistant (C3H/HeJ) mice, infection with the bacteria did not
      induce any suppression in the mitogen-induced lymphoproliferation. Likewise,
      delayed-type hypersensitivity (DTH) responses, to keyhole limpet hemocyanin and
      mycobacterial crude soluble antigen were suppressed in infected BALB/c mice but
      not in C3H/HeJ mice. This depressed T helper cell function may either be due to
      defective T cell-receptor occupancy by antigen-Ia complex or altered co
      stimulatory signals provided by antigen-presenting cells. In the present study,
      we have investigated the status of certain co-stimulatory molecules on the
      infected macrophages from both susceptible and resistant mice. Our results
      demonstrate that upon mycobacterial infection, the macrophages are rendered
      incapable of delivering the co-stimulatory signals to T helper cells, possibly
      due to the involvement of prostaglandin, as inhibition of its biosynthesis by
      indomethacin reversed the defect. Furthermore, the selective regulation was
      bacteria-induced as killing of the bacteria by rifampicin abrogated the
      derangements in the expression of co-stimulatory molecules on the Mycobacterium
      infected macrophages. Our observations revealed that upon infection with
      Mycobacterium tuberculosis, B7 was down-regulated while ICAM-1 was increased only
      in BALB/c but not in C3H/HeJ mice. Expression of VCAM-1 did not change during the
      infection in either strain of mice. We found that these changes in ICAM-1 and B7
      expression on the surface of infected macrophages resulted in inhibition of DTH
      mediating functions of T helper cells from BALB/c mice. The results obtained in
      this study describe not only a novel immune evasion strategy adopted by
      Mycobacterium, but also open up the possibility of immunotherapy of mycobacterial
      infection by selective manipulation of co-stimulatory molecules.

PMID- 7525296
TI  - Tyrosine kinase activity associated with the CD7 antigen: correlation with
      regulation of T cell integrin function.
AB  - Rapid up-regulation of the functional activity of integrin adhesion receptors is
      a hallmark of T cell activation. Monoclonal antibody engagement of the CD7
      antigen on human T cells results in an increase in beta 1 and beta 2 integrin
      mediated adhesion within minutes. This suggests that CD7 is capable of
      transducing intracellular signals, and is consistent with other indirect studies
      implicating CD7 as a signaling receptor on T cells. In this report, we have
      explored the intracellular mechanism by which CD7 modulates integrin functional
      activity. First, CD7-mediated up-regulation of T cell adhesion was found to be
      unique when compared to phorbol ester stimulation and CD3/T cell receptor cross
      linking, based on differences in the kinetics of activation-dependent integrin
      mediated adhesion and lack of increase in CD2 functional activity. Second, up
      regulation of integrin activity mediated by CD7 cross-linking was completely
      inhibited by the tyrosine kinase inhibitor herbimycin A. Third,
      antiphosphotyrosine immunoblotting demonstrated that antibody engagement of CD7
      results in a rapid but transient increase in tyrosine phosphorylation in human T
      cells. Finally, CD7 immunoprecipitates contain in vitro kinase activity, as
      demonstrated by phosphorylation of a predominant band of 80 kDa and multiple
      other bands. Phosphoamino acid analysis of the 80-kDa substrate revealed
      phosphorylation on tyrosine as well as serine and threonine residues. Together,
      our results suggest that CD7 is associated with tyrosine kinase activity and that
      this tyrosine kinase activity correlates with the ability of CD7 to regulate T
      cell integrin functional activity.

PMID- 7525298
TI  - Recognition of apoptotic cells by human macrophages: inhibition by a
      monocyte/macrophage-specific monoclonal antibody.
AB  - Cells undergoing death by apoptosis are rapidly engulfed by phagocytes in vivo, a
      highly efficient process which prevents leakage of potentially dangerous
      intracellular contents from dying cells to neighboring tissue. We have tested a
      panel of monoclonal antibodies (mAb) specifying a range of human
      monocyte/macrophage surface antigens for their capacity to inhibit the in vitro
      recognition of apoptotic cells by human peripheral blood monocyte-derived
      macrophages. The results identify the antigen defined by the 61D3 mAb, a widely
      used marker of monocyte/macrophage lineage cells, as an important mediator of
      apoptotic cell recognition. In our system, apoptotic, but not viable, cells were
      recognized by the cultured macrophages and 61D3 was found to inhibit the
      recognition of all apoptotic cell types tested, including Ca2+ ionophore-treated
      or growth factor-depleted B and T lymphocyte lines, tonsillar germinal center B
      cells, irradiated peripheral blood lymphocytes and senescing neutrophils.
      Furthermore, the apoptotic cell recognition pathway specified by 61D3 could be
      distinguished from that involving the macrophage alpha v beta 3 vitronectin
      receptor which has been shown previously to play an important role in the
      recognition of apoptotic cells. These results provide further evidence that the
      mechanisms underlying rapid clearance of apoptotic cells involve multiple
      phagocyte receptors.

PMID- 7525299
TI  - Fas ligation triggers apoptosis in macrophages but not endothelial cells.
AB  - The reticuloendothelial system includes macrophages and endothelial cells. These
      cells are produced and destroyed in vivo with a precision that implies the
      existence of homeostatic mechanisms. The stimuli for endothelial cell
      proliferation and monocyte production are becoming well characterized. However,
      the mechanisms involved in eliminating these cells are poorly understood. One
      mechanism involved in cellular elimination is apoptosis, which can be triggered
      in some cells by ligation of the Fas molecule. In this report we have
      investigated whether macrophages and endothelial cells express the Fas molecule,
      and whether Fas transmits an apoptosis-inducing signal in these cells. We
      demonstrate that macrophages express Fas and readily undergo apoptosis when
      cultured with anti-Fas. In contrast, while endothelial cells can express the Fas
      molecule, Fas ligation is insufficient to induce apoptosis. These results suggest
      differential regulation of Fas function among cells of the reticuloendothelial
      system, and imply different mechanisms of homeostasis.

PMID- 7525300
TI  - In vitro priming of cytotoxic T lymphocytes against poorly immunogenic epitopes
      by engineered antigen-presenting cells.
AB  - Cytotoxic T lymphocytes (CTL) recognize antigenic peptides presented by major
      histocompatibility complex class I (MHC-I) molecules on the surface of target
      cells. Optimal induction of CD8+ CTL depends on the amount of relevant
      peptide/MHC-I complexes and the presence of co-stimulatory molecules on antigen
      presenting cells (APC). The antigen-processing defective mutant cell line RMA-S,
      when cultured at low temperature, expresses high amounts of MHC-I molecules that
      do not contain endogenously derived peptides. These "empty" MHC-I molecules can
      be stabilized by addition of MHC-binding peptides. RMA-S cultured at low
      temperatures with selected peptides have been used for in vitro CTL induction
      with conflicting results. RMA-S cells do not express detectable amounts of B7 co
      stimulatory molecule. This could explain their unpredictable efficiency as APC.
      We have evaluated whether RMA-S cells, stably transfected with cDNA encoding for
      the human B7.1 molecule could provide effective co-stimulation for CD8+ T
      lymphocytes. RMA-S/B7 cells, loaded with different synthetic peptides,
      demonstrated a high and sometimes unique efficiency for in vitro primary CTL
      induction, even when "sub-optimal" antigen peptides were used. Most importantly,
      RMA-S/B7 cells pulsed with naturally processed peptides extracted from the poorly
      immunogenic B16 melanoma cells were able to prime CD8+ cells against B16
      melanoma. We conclude that the use of RMA-S/B7 cells as APC represents an ideal
      strategy for in vitro CTL immunization without prior in vivo priming. This system
      may also help to address the issue of the different contributions of co
      stimulation and relative occupancy of MHC-I by single peptide epitopes in CTL
      priming.

PMID- 7525301
TI  - Properties of mouse CD40: the role of homotypic adhesion in the activation of B
      cells via CD40.
AB  - Stimulation of human B cells via CD40 is known to induce their homotypic
      aggregation. We show here that anti-mouse CD40 monoclonal antibodies (mAb) also
      induce B cells to form large, spherical, extremely stable clusters. This
      clustering is markedly enhanced by co-stimulation with either interleukin-4 (IL
      4) or anti-immunoglobulin (Ig). The aggregation is slow in onset, and is largely
      (but not completely) abrogated by anti-LFA-1 mAb, but not by mAb directed against
      other potentially important adhesion molecules on B cells. Anti-LFA-1 mAb also
      partially suppressed DNA synthesis induced by anti-CD40, but not by other B cell
      mitogens, suggesting that clustering is an important component of B cell
      activation via CD40. This concept is supported by analyses of the phenotype of
      clustered B cells: the cells within clusters express higher levels of various
      activation markers, and also more of them are in cell cycle than non-clustered
      cells. These results therefore suggest that CD40 stimulation may either induce B
      cells to secrete soluble factors which act in an autocrine way to promote B cell
      activation, or that clustering generates cell contact-mediated signals which are
      important in the activation cascade.

PMID- 7525302
TI  - Localization of two cytotoxic T lymphocyte epitopes and three anchoring residues
      on a single nonameric peptide that binds to H-2Ld and is recognized by cytotoxic
      T lymphocytes against mouse tumor P815.
AB  - Mouse mastocytoma P815 expresses tumor antigens P815A and P815B encoded by a
      single gene called P1A and carried by a single peptide named P1A 35-43 (NH2-Leu
      Pro-Tyr-Leu-Gly-Trp-Leu-Val-Phe-COOH). P1A 35-43 is presented to anti-P815A and
      anti-P815B cytotoxic T lymphocytes (CTL) by major histocompatibility complex
      (MHC) H-2Ld molecules. In order to determine the individual role played by each
      amino acid residue of P1A 35-43 in binding to H-2Ld and in recognition by anti-A
      and anti-B T cell receptors (TcR), a series of P1A35-43 peptides substituted by
      alanine at single positions was synthesized and tested for binding to H-2Ld and
      for CTL recognition. Binding to H-2Ld was estimated by measuring the ability of
      the peptide to up-regulate cell surface expression of H-2Ld. We found that three
      residues were important for interaction of P1A 35-43 with H-2Ld. Two of them, Pro
      at position 2 and Phe at position 9 were consistent with the described H-2Ld
      binding motif. A third residue, Trp at position 6, was also required for
      effective MHC binding of the tumor antigen. CTL sensitization assays showed that
      alanine substitution at position 7 (Leu) or at position 8 (Val) dramatically
      affected peptide recognition by anti-A CTL while positions 3 (Tyr) and 4 (Leu)
      were critical for recognition by anti-B CTL. We conclude that Pro2, Trp6 and Phe9
      constitute the anchor residues of P1A 35-43 to H-2Ld, whereas the dipeptidyl
      sequences Tyr3-Leu4 and Leu7-Val8 form the core epitopes recognized by the TcR of
      anti-P815B and anti-P815A CTL, respectively.

PMID- 7525304
TI  - T cell regulation of collagen-induced arthritis in mice. III. Is T cell
      vaccination a valuable therapy?
AB  - Since T cells play a critical role in collagen-induced arthritis (CIA), CD4+ T
      cell hybridomas were derived from DBA/1 mice immunized with bovine type II
      collagen (CII). The hybrid clones selected were Thy-1-2+, CD4+, CD8-, T cell
      receptor (TcR) alpha beta + and produced interleukin-2 in response to CII
      peptides presented by I-Aq molecules. The clones were collagen type-specific and
      recognized CII from many species except the mouse. More precisely, the reactivity
      was directed against the immunodominant cyanogen bromide-cleaved fragment
      CB11(II). Analysis of the TcR carried by the T cell hybridomas showed that they
      used identical V alpha and J alpha (V alpha BMB, J alpha 20) gene segments and
      two distinct V beta (V beta 1 and V beta 4) associated with the J beta 2.5 gene
      segment. Interestingly, the junctional regions were highly conserved in structure
      and length. These findings may indicate a strong in vivo selection by the antigen
      for a particular combination of both alpha and beta chains of the TcR.
      Inoculation of irradiated anti-CII T cell hybrids into DBA/1 mice, before priming
      with CII, altered the course of the disease resulting in either a long-lasting
      suppression or an exacerbation of CIA whereas a control CD4+ hybridoma with an
      unrelated specificity did not influence the development of arthritis. However,
      the regulatory effect of anti-CII T cell clones was unpredictable, suggesting
      that the TcR structure may not solely account for the modulation of CIA and that
      T cell vaccination is not a reliable method for inducing suppression of CIA.

PMID- 7525305
TI  - Expression of major histocompatibility complex class II molecules in rat T cells.
AB  - The expression of major histocompatibility complex (MHC) class II molecules in
      murine T cells has been controversial. We therefore reexamined the transcription,
      synthesis and surface expression of MHC class II determinants in rat T cells both
      in vivo and in vitro. In naive rats, a large proportion of small CD4+8+ and
      mature CD4+8-/CD4-8+ thymocytes was found to be MHC class II positive. At least
      some of the MHC class II molecules found on thymocytes were actively synthesized.
      The synthesis of MHC class II proteins was detected in peripheral T cells
      activated in vivo during induction of experimental allergic encephalomyelitis
      (EAE). A proportion of T cells from the inflammatory lesion of EAE exhibited MHC
      class II on the surface. A panel of helper T cell lines and clones was shown to
      synthesize MHC class II proteins. In a prototypic clone, a weak constitutive
      expression of MHC class II was observed. During activation, the rate of
      endogenous MHC class II synthesis increased and passive absorption of surface MHC
      class II from other cells occurred. Our data demonstrate the expression of MHC
      class II molecules in rat T cells in both the thymus and periphery. Since the
      primary function of MHC class II molecules is the presentation of peptide
      epitopes to T cells, these results call attention to the possible role of MHC
      class II molecules in T-T interactions during T cell maturation and activation.

PMID- 7525306
TI  - B cell antigen receptor cross-linking induces tyrosine phosphorylation and
      membrane translocation of a multimeric Shc complex that is augmented by CD19 co
      ligation.
AB  - The SH2 domain-containing transforming Shc protein has been implicated in
      mitogenic signaling via several surface receptors through p21ras. Following
      tyrosine phosphorylation by either receptor or non-receptor tyrosine kinases, Shc
      may interact with the adaptor protein Grb2, which is linked to Sos1, a guanine
      nucleotide exchange factor for human ras. Ligation of the antigen receptor
      complex on B cells (BCR) is known to activate various intracellular signaling
      pathways, which may accumulate in mitogenic responses. With respect to the
      initial steps, the activation of BCR-associated non-receptor tyrosine kinases
      appears to be indispensible. In this report we show that Shc proteins become
      tyrosine phosphorylated after BCR ligation on both transformed and normal human B
      cells. This is accompanied by the association of Shc with Grb2 proteins and a yet
      unidentified 145-kDa tyrosine phosphorylated protein. Subcellular fractionation
      revealed that this activation-induced multimeric Shc complex rapidly translocates
      towards the plasma membrane. Co-ligation of the BCR with the CD19 molecule
      results in a marked increase of these events, whereas CD19 cross-linking alone
      does not induce Shc tyrosine phosphorylation or translocation. Thus, in B cells
      the Shc complex may represent a molecular junction between the BCR and the
      mitogenic p21ras cascade.

PMID- 7525308
TI  - Deficient expression of co-stimulatory molecules on Leishmania-infected
      macrophages.
AB  - Co-stimulatory signals are necessary for the full activation of T cells for
      growth and effector function. As co-stimulatory molecules are normally regulated
      in their expression, it has been suggested that microorganisms enhance their
      expression on host antigen-presenting cells (APC), thus allowing efficient
      generation of anti-microbial immunity. We here describe experiments which
      demonstrate that infection of macrophages, both in vitro and in vivo, by the
      protozoan parasite Leishmania donovani fails to trigger expression of co
      stimulatory molecules B7-1 and heat-stable antigen on these APC. Furthermore,
      infection with this parasite inhibits the macrophage response to normal
      regulatory signals, such as bacterial lipopolysaccharide. These changes in the
      cell surface are mirrored in functional studies of co-stimulation in vitro.
      Together, these data suggest a further facet of parasite interference in host
      immunity, but also indicate a potential new target for immunotherapy.

PMID- 7525303
TI  - The expansion of a CD4+ T cell population bearing a distinctive beta chain in MRL
      lpr/lpr mice suggests a role for the fas protein in peripheral T cell selection.
AB  - MRL lpr/lpr mice suffer from a systemic lupus erythematosus-like autoimmune
      disease. The lpr mutation impairs the normal transcription of the fas message,
      the product of which mediates apoptosis and presumably the proper selection of T
      cells. We have found an early expansion of CD4+ T cells bearing a distinctive V
      beta 8.3-D beta 1.1-J beta 1.1 T cell receptor beta chain in the periphery of MRL
      lpr/lpr mice, which was not detected in MRL +/+ mice nor in the thymus of MRL
      lpr/lpr mice. Thus, since thymic selection is normal in MRL lpr/lpr mice, we
      propose that the lpr mutation results in defective negative selection at the
      periphery.

PMID- 7525307
TI  - Distinct structural and functional epitopes of the alpha E beta 7 integrin.
AB  - Intestinal intraepithelial lymphocytes (iIEL) are predominantly CD3+, CD8+ T
      lymphocytes located above or adjacent to the mucosal basement membrane. Although
      they are positioned to interact with intercellular luminal antigen or with
      enterocytes, the function of iIEL remains unknown. Most (> 85%) of the iIEL
      express the alpha E beta 7 integrin which appears to be involved in the adhesion
      of lymphocytes to epithelial cells. We report the characterization of three
      monoclonal antibodies (mAb) termed alpha E7-1, alpha E7-2, and alpha E7-3, that
      react with the alpha E beta 7 integrin recognized by the previously described mAb
      HML-1 as demonstrated by identical sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis mobility and charge. Flow cytometric analysis of antibody cross
      blocking indicated that these mAb recognize distinct epitopes of alpha E beta 7.
      While all of the mAb were capable of blocking the adhesion of cultured iIEL to a
      breast epithelial cell line, only HML-1 and alpha E7-1 (which recognize an
      identical or closely related epitope) were co-stimulatory with suboptimal
      concentrations of anti-CD3 mAb in inducing proliferation of cultured iIEL. Thus,
      these mAb appear to recognize functionally distinct epitopes of alpha E beta 7
      and will be useful to study relationships between the structure and function of
      this integrin.

PMID- 7525309
TI  - Antigenic and immunogenic mimicry of the HER2/neu oncoprotein by phage-displayed
      peptides.
AB  - To recover peptides that antigenically and immunogenically mimic the p185HER2
      oncoprotein, we selected the phage-peptide libraries pVIII-9aa and pVIII-9aa. Cys
      using murine monoclonal antibodies (mAb) MGr2 and MGr6, directed against two
      distinct epitopes of the p185HER2 extracellular domain. Phage-displayed peptides
      containing consensus amino acid motifs were recovered and shown to compete
      specifically for mAb binding on tumor cells that overexpress p185HER2. The
      deduced amino acid sequence of the peptides suggests that both epitopes defined
      by the mAb on p185HER2 are discontinuous and that hydrophobic interactions are
      involved in binding with the mAb. A phage clone displaying the GPLDSLFAQ peptide
      elicited a specific immune response against the p185HER2 in BALB/c mice,
      demonstrating that this phage-displayed peptide represents an immunological
      equivalent of the MGr2 epitope on p185HER2 and might be used as a substitute for
      this oncoprotein in in vitro and in vivo immunological studies.

PMID- 7525310
TI  - An inhibitor of cytotoxic functions produced by CD8+CD57+ T lymphocytes from
      patients suffering from AIDS and immunosuppressed bone marrow recipients.
AB  - An inhibitor of the cytotoxic functions (ICF) mediated by human immunodeficiency
      virus (HIV)- or HLA-specific cytotoxic T lymphocytes, natural killer and
      lymphokine-activated killer (LAK) cells is secreted by CD8+CD57+ T lymphocytes, a
      subset expanded during infection with HIV and after bone marrow transplantation.
      We previously showed an apparent molecular mass of 20-30 kDa for this soluble
      glycosylated concanavalin A-binding inhibitor which is distinct from known
      cytokines. Here, we report a characterization of the mechanism of action of this
      CD8+CD57+ ICF. We show that the ICF-induced inhibition of LAK cell cytolytic
      activity is transient, with a spontaneous recovery of cytolytic potential after
      18 h. When testing interactions of ICF with a large set of cytokines we found
      that the ICF-mediated inhibition of cytotoxic functions is antagonized by two
      cytokines: recombinant interleukin (rIL)-4 and recombinant interferon (rIFN)
      gamma. Finally, we show that ICF acts at the level of cytolytic effector cells,
      where it induces a significant increase of cyclic AMP (cAMP) level. In contrast,
      no modification of either cell surface antigen expression or of target/effector
      cell conjugate formation could be evidenced. Addition of rIL-4 and rIFN-gamma
      reverses such an increase of cAMP levels and in parallel restores the cytolytic
      activity. Altogether, these data demonstrate that the glycoprotein ICF produced
      by CD8+CD57+ cells (1) inhibits cell-mediated cytotoxicity by sensitizing
      cytolytic effector cells to the cAMP pathway, and (2) is part of a cytokine
      network controlling cell-mediated cytotoxic functions.

PMID- 7525311
TI  - CD8high (CD57+) T cells in normal, healthy individuals specifically suppress the
      generation of cytotoxic T lymphocytes to Epstein-Barr virus-transformed B cell
      lines.
AB  - We have previously identified two subsets of CD8+, CD57+ lymphocytes in normal
      peripheral blood: i) T cells expressing high levels [CD8high(CD57+)] and ii)
      natural killer cells expressing low levels of surface CD8[CD8low(CD57+)]. We
      investigated the cytotoxic and suppressive function of CD8high(CD57+) T
      lymphocytes from normal, healthy individuals using standard chromium-release
      assays and limiting dilution analysis. In normal, healthy subjects, this cell
      subset suppressed the generation of cytotoxic T lymphocytes (CTL) to autologous,
      Epstein-Barr virus (EBV)-transformed B cell lines (BCL). Depletion of
      CD8high(CD57+) T lymphocytes from peripheral blood mononuclear cells (PBMC)
      resulted in a three- to sevenfold rise in CTL precursor frequency to autologous
      EBV-transformed BCL, but not allogeneic PBMC or BCL by LDA. Replacement of
      CD8high(CD57+) T lymphocytes in limiting dilution cultures led to the dose
      dependent suppression of EBV-specific, but not allogeneic, CTL generation.
      Supernatant from CD8high(CD57+) T lymphocytes cultured with autologous BCL did
      not exhibit suppression, suggesting that soluble factors were not responsible. As
      CD8high(CD57+) T lymphocytes did not, themselves, exhibit cytotoxicity against
      autologous BCL, removal of BCL stimulator cells in co-culture was not the
      mechanism of suppression. Furthermore, while the CD8high(CD57+) T lymphocytes
      from healthy subjects suppressed the generation of CTL to autologous BCL, they
      did not suppress the cytotoxic activity of established mixed lymphocyte reactions
      or peptide-specific CTL clones, as has been reported in bone marrow transplant
      recipients and human immunodeficiency virus patients. This suggests that
      CD8high(CD57+) T lymphocytes from healthy subjects suppress the generation of,
      rather than killing by, CTL in a contact-dependent manner. To our knowledge, this
      is the first identification of a phenotypically distinct subset of human CD8+ T
      cells that can suppress generation of antigen-specific major histocompatibility
      complex class I-restricted CTL.

PMID- 7525312
TI  - Galanin message-associated polypeptide (GMAP) does not affect insulin secretion
      from isolated islets.
AB  - Galanin message-associated polypeptide (GMAP) is processed from preprogalanin.
      Recently, GMAP-like immunoreactivity was demonstrated in insulin cells in the
      endocrine pancreas. We therefore examined whether synthetic rat GMAP, like
      galanin, inhibits glucose-stimulated insulin secretion from isolated rat and
      mouse islets. We found, however, that over a wide dose range (0.1 nM to 1 microM)
      GMAP did not affect insulin secretion stimulated by 8.3 or 11.1 mM glucose during
      a 60-min incubation of single rat or mouse islets. In contrast, rat galanin, as
      expected, completely abolished glucose-stimulated insulin secretion at 100 nM.
      Thus, in contrast to galanin, GMAP does not affect insulin secretion in isolated
      rodent islets.

PMID- 7525313
TI  - Substance P N-terminus inhibits C-fiber-dependent facilitation of the rat flexor
      reflex.
AB  - Substance P injected intrathecally or a conditioning stimulus (1 Hz, 20 s) at C
      fiber strength, which releases substance P from intraspinal primary afferent
      terminals, each enhance the hamstring muscle flexor reflex elicited by electrical
      stimulation of the sural nerve in decerebrate, spinalized rats. This suggests a
      role for substance P in pain transmission. Since substance P N-terminal
      metabolites are biologically active, we examined the effect of the metabolite
      substance P-(1-7) on the flexor reflex and the enhancement of the flexor reflex
      following a conditioning stimulus of the sural nerve. In contrast to the
      excitatory effect of substance P, intrathecal injection of substance P-(1-7) had
      no effect on the flexor reflex. However, 10 and 30 min after injection, 0.6 or 6
      micrograms of substance P-(1-7) attenuated the facilitation of the flexor reflex
      by the conditioning stimulus. These data indicate that substance P-(1-7) may
      modulate the expression of nociception involving repetitive firing of C-fibers
      while having no significant effect on acute or phasic responses.

PMID- 7525314
TI  - Biological activities of two endogenously occurring N-terminally extended forms
      of galanin in the rat spinal cord.
AB  - The occurrence of two N-terminally extended forms of galanin in the porcine
      adrenal medulla was reported earlier by Bersani et al. (1991). We have
      synthesized and examined the ability of these two extended forms of galanin,
      galanin-(-7-29) and galanin-(-9-29), to bind to galanin receptors in the rat
      dorsal spinal cord. The effect of intrathecal (i.t.) injection of these peptides
      on spinal flexor reflex excitability in decerebrate, spinalized, unanesthetized
      rats was also studied. Both galanin-(-7-29) and galanin-(-9-29) fully displaced
      specific 125I-monoido-[Tyr26]porcine galanin (125I-galanin) binding to membranes
      prepared from rat dorsal spinal cord, with IC50 values 0.13 and 0.14 microM,
      respectively. The metabolic half-lives in spinal cord membranes for galanin-(1
      29), galanin-(-7-29) and galanin-(-9-29) were 117 +/- 17, 271 +/- 23 and 185 +/-
      19 min, respectively. I.t. injection of galanin-(-7-29) and galanin-(-9-29)
      mimicked the biphasic facilitatory and inhibitory effect of i.t. galanin-(1-29)
      on flexor reflex excitability and antagonized C-fiber conditioning stimulus
      induced spinal cord hyperexcitability, but with reduced potencies compared to
      galanin-(1-29). We suggest that the N-terminally extended forms of galanin act as
      endogenous ligands with low agonist activity.

PMID- 7525315
TI  - Tachykinin NK1 and NK2 receptors mediate atropine-resistant ileal circular muscle
      contractions evoked by capsaicin.
AB  - The atropine-resistant contractile action of the sensory stimulant drug capsaicin
      was examined on guinea-pig ileum circular muscle in vitro, with special regard to
      the involvement of endogenous tachykinins acting through tachykinin NK1 and NK2
      receptors. A protocol, using ruthenium red was developed for overcoming
      desensitization to capsaicin so that two reproducible responses to this drug were
      obtained. Capsaicin (10(-6) M) caused tonic and phasic contractions of the
      tissue. This effect was significantly inhibited by the tachykinin NK1 receptor
      blocking drug FK 888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L
      proly]-N- methyl-N-phenylmethyl-3-(-2-naphthyl)-L-alaninamide) or the tachykinin
      NK2 receptor inhibitor GR 94,800 (PhCO-Ala-Ala-D.Trp-Phe-D.Pro-Pro-NleNH2) (10(
      6) M each) and was practically abolished by the combined administration of the
      two tachykinin receptor blockers. Likewise, the neuronal Na+ channel inhibitor
      tetrodotoxin abolished the response to capsaicin. It is concluded that the
      contractile effect of capsaicin in the circular muscle is predominantly mediated
      by tachykinin release and both subtypes of tachykinin receptor (NK1 and NK2) play
      an important role in this process. The source of tachykinins, however, is
      probably intrinsic neurons of the myenteric plexus, indirectly activated by
      capsaicin-sensitive nerves, as shown by the sensitivity of the response to
      tetrodotoxin.

PMID- 7525316
TI  - Angiotensin AT1 receptor blockade by specific antibody prevented two-kidney, one
      clip renal hypertension in the rat.
AB  - The effect of chronic angiotensin AT1 receptor blockade by a specific antibody on
      the development of two-kidney, one-clip renal hypertension was studied in Wistar
      rats. Renal artery constriction resulted in a fast and large increase in blood
      pressure in comparison with that of control rats. On the other hand, the pre
      immunization of rats with a small part of the angiotensin AT1 receptor completely
      prevented the development of renal hypertension. We conclude that the development
      of two-kidney, one-clip renal hypertension can be blocked by a specific antibody
      raised against a part of the angiotensin AT1 receptor.

PMID- 7525317
TI  - Gs alpha-dependent and -independent desensitisation of prostanoid IP receptor
      activated adenylyl cyclase in NG108-15 cells.
AB  - NG108-15 mouse neuroblastoma x rat glioma cells were treated with the prostanoid
      IP receptor agonist iloprost (1 microM) and the time course of changes in the
      levels of prostanoid IP receptors, adenylyl cyclase activity, and the alpha
      subunit of the stimulatory guanine nucleotide binding regulatory protein, Gs,
      were measured. Incubation of cells with iloprost produced a biphasic time course
      of desensitisation of prostanoid IP receptor-activated adenylyl cyclase. Parallel
      analysis of iloprost-induced loss of membrane Gs alpha, NaF-stimulated adenylyl
      cyclase and [3H]iloprost binding suggested only monophasic curves, with t0.5
      values similar to the initial phase of desensitisation of iloprost-stimulated
      adenylyl cyclase activity. This suggests that the loss of receptor and Gs alpha
      occur at the same time and account for the initial period of desensitisation due
      to iloprost pretreatment. Pretreatment of NG108-15 cells with cholera toxin
      produced a near complete loss of membrane-associated Gs alpha, but the loss of
      [3H]iloprost binding due to iloprost treatment was not affected by pretreatment
      with cholera toxin, suggesting that prostanoid IP receptors can be down-regulated
      in the absence of any coupling to Gs. The second phase of desensitisation of
      iloprost-stimulated adenylyl cyclase activity, during which there was no further
      change in NaF-stimulated adenylyl cyclase or in the membrane levels of Gs alpha,
      was not due to protein kinase A activation, since elevating intracellular cyclic
      AMP levels with forskolin did not subsequently decrease iloprost-stimulated
      adenylyl cyclase activity or [3H]iloprost binding. These results demonstrate that
      iloprost pretreatment of NG108-15 cells induces two distinct phases of
      desensitisation; an initial desensitisation due to concurrent loss of prostanoid
      IP receptors and Gs alpha, and then a further desensitisation by an as yet
      uncharacterized mechanism during which there is no further loss of Gs alpha.

PMID- 7525318
TI  - Dual modulation by adenosine of ATP-activated channels through GTP-binding
      proteins in rat pheochromocytoma PC12 cells.
AB  - Effects of adenosine on inward current activated by extracellular ATP were
      examined in rat pheochromocytoma PC12 cells. Adenosine induced two types of
      modulation on the current activated by 30 microM ATP; a low concentration of
      adenosine (1 microM) inhibited the current whereas a high concentration (> 10
      microM) enhanced the current. Neither the inhibition nor the enhancement was
      observed in cells pretreated with pertussis toxin (PTX), or in cells dialyzed
      with guanosine 5'-O-(2-thiotriphosphate) trilithium salt (GDP beta S). In
      contrast, dialysis with K-252a, a protein kinase inhibitor, abolished the
      inhibition, but not the enhancement. Adenosine induced similar inhibition and
      enhancement on ATP-evoked increase in intracellular free Ca2+ concentration. The
      results suggest that adenosine produces dual modulation on the ATP-activated
      channels through different mechanisms involving PTX-sensitive GTP-binding
      proteins.

PMID- 7525319
TI  - Root resorption beneath the main hyalinized zone.
AB  - A previous investigation on the initial phase of root resorption associated with
      orthodontic overcompression of local areas of the periodontal ligament (PDL),
      indicated that a differentiation should be made between two stages: (1) the very
      first resorption occurring in the periphery of the main necrotic zone; and (2)
      the root resorption occurring on that part of the root surface situated beneath
      the main bulk of necrotic tissue (Brudvik and Rygh, 1993a). The aim of the
      present investigation was to study the latter stage. Attention was focused on:
      (1) the possible association between the presence of necrotic tissue and root
      resorption; and (2) the cells that invaded and removed the necrotic tissue, as
      well as the cells that started to remove/resorb the cementum. Mesial movement of
      the upper first molars (rats) and lower first molars (mice) was performed by a
      fixed orthodontic appliance. The results indicate an association between the root
      resorption, and the presence and active removal of the hyalinized tissue. Root
      resorption beneath the main hyalinized zone occurred in areas where invading
      cells were observed close to the root surface. The majority of the cells involved
      in removal of the necrotic tissue and resorption of the root surface were multi
      nucleated and TRAP-positive. It is hypothesized that multi-nucleated TRAP
      positive cells when reaching the subjacent contaminated and damaged root surface
      after having removed necrotic PM tissue, continued to remove the cementum
      surface.

PMID- 7525321
TI  - Involvement of molecular chaperones in the aberrant aggregation of secretory
      proteins in pancreatic acinar cells.
AB  - Molecular chaperones have recently been shown to be accurately located along
      distinct cellular compartments of the secretory pathway of pancreatic acinar
      cells. Since the aberrant aggregation of secretory proteins leading to the
      formation of RER intracisternal crystals induced by DL-p-chlorophenylalanine
      methyl ester (CPME) comprises major changes in the sorting, selective transport,
      and/or posttranslational modifications of secretory proteins, we decided to
      investigate the possible involvement of chaperones in this phenomenon by applying
      the protein A-gold immunocytochemical approach. In addition to their presence in
      the cellular compartments of the secretory pathway, the chaperonins cpn10 and
      cpn60 were found to also be concentrated in the RER intracisternal crystals. In
      contrast, the hsp70 protein remained confined to the trans-Golgi network and was
      absent from the crystals. In both control and experimental conditions the three
      chaperones were present in mitochondria. Quantitative evaluations confirmed these
      observations and revealed an overall decrease in the labeling, particularly for
      hsp70 after CPME treatment. These labeling patterns suggest a participation of
      the chaperonins cpn10 and cpn60 but not of the hsp70 in the aberrant aggregation
      of secretory proteins leading to RER crystal formation. The role played by
      chaperones in this process, however, remains to be elucidated.

PMID- 7525322
TI  - Density-dependent inhibition of mouse embryo fibroblast growth: involvement of
      IGFBP-3.
AB  - Up until now the phenomenon of density dependent inhibition of growth has
      remained unexplained; one hypothesis suggests that autocrine growth inhibitory
      molecules are secreted in the medium of dense cultures and inhibit cell growth.
      From medium conditioned by mouse fibroblasts we purified a 45-kDa inhibitory
      factor which is an insulin-like growth factor binding protein (IGFBP-3). Based on
      different results we assumed that IGFBP-3 is a bifunctional molecule and has
      inhibitory function independent of its known function of binding IGF. In the
      present publication we attempted to verify whether IGFBP-3 is involved in DDI of
      growth. IGFBP-3 was secreted by mouse embryo fibroblasts (MEF). Its concentration
      in the medium increased with the cell density of the culture and was large at
      saturation density when DNA synthesis was minimum. Medium conditioned (CM) by
      dense culture was inhibitory compared to fresh medium and this inhibition
      disappeared when CM was preincubated with anti-IGFBP-3 IgG. Addition of FGFb to
      MEF dense cultures increased but transiently DNA synthesis which decreased as
      soon as 24 h after growth factor addition. By contrast accumulation of IGFBP-3 in
      the medium increased with time and was large at the time when DNA synthesis was
      minimum. Our results suggest that the rapid decrease of DNA synthesis in
      stimulated dense culture was the result of both depletion of the medium
      (particularly of FGFb) and the increase in concentration of inhibitory molecules
      like IGFBP-3. Addition of FGFb and preincubation of CM with anti-IGFBP-3 IgG were
      able to greatly reduce the inhibition.

PMID- 7525320
TI  - Multi-nucleated cells remove the main hyalinized tissue and start resorption of
      adjacent root surfaces.
AB  - Recent studies revealed that the initial root resorption occurred in the
      peripheries of the necrotic periodontal ligament (PDL) and was performed by mono
      nucleated non-clast macrophage- and fibroblast-like cells (Brudvik and Rygh,
      1993a, b). The aim of the present transmission electron microscopic (TEM)
      investigation was to study in more detail the cells involved in removal of the
      main hyalinized tissue and those involved in root resorption, occurring on the
      root surface situated beneath the main hyalinized tissue. Twelve male Wistar rats
      were used. The maxillary first molar was moved mesially by a fixed orthodontic
      appliance for 7 and 10 days. The results indicate that multi-nucleated giant
      cells (MNGC) without a ruffled border surface, as well as mono-nucleated
      macrophage-like cells were responsible for removal of the necrotic tissue and
      also for resorption of the surface parts of the root cementum. Although the
      present MNGC showed many morphological traits similar to the observed
      odontoclasts and osteoclasts, except for their lack of ruffled borders, it is
      assumed that they are derived from the mono-nucleated phagocytic system. Multi
      nucleated clast-like cells with ruffled border were never observed near the
      remnants of the necrotic tissue. Such cells were found only in the resorption
      lacunae on root and bone surfaces.

PMID- 7525323
TI  - PGE2 induces c-fos expression by a cAMP-independent mechanism in glomerular
      mesangial cells.
AB  - Prostanoids induce expression of several immediate-early genes, but the molecular
      mechanisms underlying these responses remain poorly characterized. We studied
      induction of the proto-oncogene c-fos by PGE2 in mesangial cells as a model of
      gene regulation by prostanoids. PGE2 induced marked and transient accumulation of
      c-fos mRNA. Addition of exogenous 8-bromo-cAMP or forskolin failed to induce c
      fos mRNA, suggesting that activation of an EP2 receptor linked to adenylate
      cyclase did not account for induction of c-fos by PGE2. These data contrast with
      previous experiments in NIH 3T3 cells in which PGE2 induced c-fos by a cAMP
      dependent mechanism. Depletion of protein kinase C blocked induction of c-fos
      mRNA by PGE2, whereas a protein tyrosine kinase inhibitor had no effect. We
      further showed that PGE2 induces the c-fos gene by increasing the transactivating
      capacity of the serum-response element. Transient transfections with a CAT fusion
      gene driven by an AP-1 cis-element demonstrated that although PGE2 markedly
      induced c-fos, PGE2 did not increase AP-1-driven transcriptional responses.
      Electrophoretic gel mobility shift assays revealed that PGE2 failed to increase
      binding of AP-1 complexes to a consensus AP-1 DNA sequence. Taken together, these
      experiments provide evidence for a cAMP-independent, protein kinase C-dependent
      pathway linking a PGE2 receptor on the plasma membrane to transcriptional
      activation in the nucleus. Regulation of gene transcription by PGE2 probably
      involves c-fos induction without concomitant activation of AP-1.

PMID- 7525324
TI  - Effect of transforming growth factor-beta on the insulin-like growth factor-I
      autocrine/paracrine axis in cultured rat articular chondrocytes.
AB  - Transforming growth factor-beta (TGF-beta) and insulin-like growth factor-I (IGF
      I) are essential anabolic factors in articular cartilage. In this study, we
      concentrated on the elucidation of TGF-beta interaction with IGF-I on cell growth
      and differentiation in monolayer articular chondrocytes obtained from 5-week-old
      rats. TGF-beta (1 ng/ml) and IGF-I (25 ng/ml) stimulated DNA synthesis about 6.5-
      and 2.1-fold over control values, respectively. When TGF-beta and IGF-I were
      added in combination, DNA synthesis was enhanced about 10.4-fold, indicating that
      the two peptides act in synergism. This synergistic action was also present in
      the expression of aggrecan mRNA. To study the mechanism of synergistic action,
      the effect of TGF-beta on the IGF-I autocrine/paracrine axis was investigated.
      Administration of increasing concentrations of TGF-beta (0.1-10 ng/ml) resulted
      in a dose-dependent decrease in medium IGF-I concentration that was reflected by
      decreased levels of IGF-I mRNA. TGF-beta also inhibited the production of a 41
      kDa IGF-binding protein into the culture medium. Pretreatment with TGF-beta (1
      ng/ml) for 12 h increased the binding of [125I]IGF-I to 140% of control by
      increasing the number of receptors without changes of affinity.
      Immunoprecipitation against phosphorylated tyrosine indicated that IGF-I
      dependent autophosphorylation of IGF-I receptor beta-subunit was inhibited by
      simultaneous TGF-beta stimulation. These observations demonstrate that TGF-beta
      acts synergistically with IGF-I and regulates the IGF-I autocrine/paracrine axis
      via a complex regulatory mechanism with decreased production of IGF-I and IGFBPs
      and dephosphorylation of IGF-I receptor, whereas there is an apparent up
      regulation of the binding of [125I]IGF-I.

PMID- 7525325
TI  - Chemotactic factor receptor activation transiently impairs the Ca2+ signaling
      capacity of beta 2 integrins on human neutrophils.
AB  - Neutrophil motility involves a delicate interplay between intracellular signals
      elicited by adhesion and chemotactic factor receptors. To explore certain aspects
      of these complex receptor interactions in neutrophils, we studied how engagement
      of the chemotactic receptor for N-formyl-L-methionyl-L-leucyl-L-phenylalanine
      (fMet-Leu-Phe) and the beta 2 integrins affect the Ca2+ signaling properties of
      each other. Specific antibody engagement of the beta 2 integrins on suspended
      neutrophils generated both an intracellular mobilization and an influx of Ca2+,
      effects which could be temporarily impaired by preengaging the fMet-Leu-Phe
      receptors on the cells. In contrast to these findings, preengagement of the beta
      2 integrins on suspended neutrophils affected neither a subsequent fMet-Leu-Phe
      induced mobilization of Ca2+ nor an influx of Ca2+ from outside the cell. We also
      found that fMet-Leu-Phe could mobilize intracellular Ca2+ after a premobilization
      of Ca2+ via beta 2 integrins, despite the fact that both receptors mobilize Ca2+
      from thapsigargin-sensitive intracellular stores. The findings that preactivation
      of beta 2 integrins did not affect the ability of fMet-Leu-Phe to induce an
      intracellular Ca2+ signal, whereas preactivation of fMet-Leu-Phe receptors
      transiently impaired the Ca2+ signaling ability of beta 2 integrins, suggest that
      the fMet-Leu-Phe-induced reduction is due to an interaction upstream of the
      release of Ca2+ from intracellular stores.

PMID- 7525327
TI  - The effect of cytokines on CD34+ Rh-123high and low progenitor cells from human
      umbilical cord blood.
AB  - In this study, we show how Rhodamine-123 (Rh-123), as in other hematopoietic
      populations, can be used to define functionally distinct progenitor cells from
      human umbilical cord blood (HUCB). CD34+ cells were subdivided into Rh-123high
      (78.2 +/- 4.5%) and Rh-123low (21.8 +/- 3.6%). While 9.3 +/- 1.6% of the CD34+Rh
      123high cells formed colonies in agar, only 0.4 +/- 0.2% of the CD34+Rh-123low
      population did so. However, the CD34+Rh-123low cells resulted in the greatest
      expansion of colony-forming cells (CFC) when cultured in liquid medium with
      different cytokine combinations. When the CD34+Rh-123low cells were cultured for
      7 days with stem cell factor (SCF) and erythropoietin (Epo), the CD34+Rh-123low
      cells resulted in a 94-fold increase in CFC compared with a 2.5-fold increase
      from the CD34+Rh-123high cells. The combination of SCF and Epo or granulocyte
      macrophage colony-stimulating factor (GM-CSF) supported the production and
      maintenance of CFC from CD34+Rh-123low cells > 28 days compared with only 21 days
      for the CD34+Rh-123high cells. Coculture of CD34+Rh-123low cells with stromal
      cell line 11 (SCL11) demonstrated that long-term culture initiating cells (LTCIC)
      were present within this population, as CFC could be recovered for > 10 weeks
      compared with < 6 weeks in cocultures with CD34+Rh-123high cells. The duration of
      maintenance of CFC in liquid culture could be further enhanced by the addition of
      an antibody (Ab) directed against the binding site of the GM-CSF receptor. The
      addition of anti-GM-CSF receptor Ab to cultures of CD34+Rh-123high and low cells
      supplemented with SCF, interleukin-3 (IL-3), and IL-6 resulted in an initial 10
      fold decrease in CFC in cultures of both the CD34+Rh-123high and low cells.
      Although very few CFCs were present by 42 days in liquid cultures of CD34+Rh
      123high cells, the number of CFCs in these cultures was significantly increased
      when anti-GM-CSF receptor Ab was added. Although this effect was also observed in
      cultures of CD34+Rh-123low cells, it was less dramatic as more CFC persisted even
      in the absence of Ab. The possible mechanism of this effect is discussed.

PMID- 7525328
TI  - Rapid exit from G0/G1 phases of cell cycle in response to stem cell factor
      confers on umbilical cord blood CD34+ cells an enhanced ex vivo expansion
      potential.
AB  - Currently, the most commonly used grafts of progenitor and stem cells for
      patients undergoing bone marrow transplantation (BMT) are derived from large
      collections of autologous or allogeneic adult human bone marrow (BM). The
      feasibility of using human umbilical cord blood (HUCB), normal peripheral blood
      (PB), and smaller collections of BM as sources of hematopoietic stem cell grafts
      for adult patients remains questionable. We investigated the ex vivo
      proliferative potential of HUCB CD34+ cells as a means of expanding HUCB grafts,
      thereby making them more acceptable for clinical transplantation. HUCB-derived
      CD34+HLA-DR+ cells, maintained for 5 days in suspension cultures supplemented
      with 10% HUCB plasma and a combination of stem cell factor (SCF) and interleukin
      3 (IL-3), displayed a 10-fold increase in the total number of CD34+ cells. In
      contrast, only a four-fold increase was observed in identical cultures initiated
      with BM-derived CD34+HLA-DR+ cells. Whereas BM CD34+ cells failed to proliferate
      in response to SCF alone, HUCB CD34+ cells expanded 5.6-fold by day 5, thus
      demonstrating an enhanced response to SCF. When the effects of SCF on the exit of
      HUCB cells from G0/G1 phases of cell cycle were investigated, we found that
      although HUCB CD34+HLA-DR+ cells were more quiescent than BM CD34+HLA-DR+ and BM
      CD34+HLA-DR- cells (97.5% of HUCB CD34+HLA-DR+ in G0/G1 vs. 88.6% of BM CD34+HLA
      DR+ and 92.0% of BM CD34+HLA-DR- [p < 0.005]), HUCB CD34+HLA-DR+ cells exited
      from dormancy more rapidly than BM cells, such that by 36 to 48 hours following
      exposure to SCF, only 55% remained in G0/G1. Furthermore, an 8.4-fold increase in
      the number of HUCB CD34+ cells still residing in G0/G1 was observed on day 5 in
      cultures supplemented with SCF and IL-3, suggesting the generation of large
      numbers of primitive hematopoietic progenitor cells (HPC) in vitro. When the
      contribution of HUCB plasma to the exist of HUCB CD34+HLA-DR+ cells from G0/G1
      phases of cell cycle was investigated, it was found that in serum-free media
      supplemented with only SCF or IL-3, HUCB cells did not exist G0/G1 as rapidly as
      when HUCB plasma or SCF plus IL-3 was present. In contrast, when HUCB plasma was
      added to any cytokine combination, it did not enhance the exist of BM CD34+HLA
      DR+ cells from G0/G1 phases of cell cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525329
TI  - In vitro proliferation by cells mobilized into the peripheral blood for
      collection and autologous transplantation.
AB  - We have investigated the properties of mobilized, cryopreserved, peripheral blood
      stem cells (PBSC), collected by leukapheresis over a period of 5 days, from eight
      myeloma patients in clinical remission. Cells were mobilized by treatment with
      cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), and each
      day's collection was evaluated for its content of CD34+ cells, colony-forming
      units granulocyte/macrophage (CFU-GM), and plastic-adherent pre-CFU-GM. Peak
      values for these three parameters were observed at different times in different
      patients. There was no correlation between CD34+ content and CFU-GM, but there
      was some (r = 0.65) between CD34 numbers and colonies generated from a delta
      assay initiated using plastic-adherent pre-CFU-GM. In suspension cultures, the
      cells grew exponentially for 50 days. Thereafter, they did not divide, although
      they remained viable in culture for up to 1 month longer. Suspension cultures of
      PBSC grown with interleukin-3 (IL-3) displayed a predominantly myelomonocytic
      phenotype, but some megakaryocytes and erythroid cells were observed
      consistently. These results indicate that pre-CFU-GM in PBSC collections are
      capable of generating large numbers of clonogenic progeny in liquid culture and
      are capable of producing multiple lineages of differentiation.

PMID- 7525326
TI  - Reciprocal interactions between human ovarian surface epithelial cells and
      adjacent extracellular matrix.
AB  - The human ovarian surface epithelium (OSE), or ovarian mesothelium, is
      functionally complex as seen by its capacity to proliferate, migrate, and
      contribute to ovulation and ovulatory repair in response to cyclic hormonal and
      environmental changes. We wished to determine whether this phenotypic versatility
      is reflected in cell-extracellular matrix interactions in primary and low-passage
      culture. Comparisons of cultures maintained on different substrata revealed that
      these cells form cohesive monolayers on plastic, while fibrin clots enhance cell
      dispersion, and thus may provide a migratory cue. The cells invaded Matrigel as
      multicellular aggregates, while collagen gels mediated a morphologic epithelial
      mesenchymal conversion. On plastic, the cells produced extracellular matrix
      components characteristic of epithelial basement membrane (laminin and collagen
      type IV), as well as stroma (collagen types I and III). In addition, ovarian
      surface epithelial cells secreted serine proteases and matrix metalloproteinases.
      The levels of chymotrypsin- and elastase-like proteases were dictated by the
      substratum: low levels were secreted by cells grown on plastic, intermediate
      levels on collagen gels and fibrin clots, and most protease was produced on
      Matrigel. The rate of cell proliferation varied with the substrata and was
      inversely related to protease secretion. Integrin expression was greatest on
      plastic and least on collagen gels where integrins were downregulated with time.
      alpha 6/beta 4 was absent from all cells while varying levels of alpha 2, alpha
      3, alpha 5, beta 1, and vitronectin receptor were detected depending on the
      culture substratum employed. In low-passage cultures of human ovarian surface
      epithelial cells, then, cell shape, growth, protease production, and integrin
      expression are modulated by the extracellular matrix. The cells, in turn, alter
      extracellular matrix by synthesis, lysis, and physical remodeling, and express
      both stromal and epithelial characteristics. The broad repertoire of these
      functions may be related to their mesodermal origin, and may reflect the
      expression of a dual, epithelio-mesenchymal phenotype by relatively immature,
      uncommitted cells. The results demonstrate the great complexity and versatility
      of these interactions which render OSE cells capable of participating in numerous
      physiological and pathological processes.

PMID- 7525330
TI  - Inhibitory effects of HIV-1-infected stromal cell layers on the production of
      myeloid progenitor cells in human long-term bone marrow cultures.
AB  - This report presents the results of studies using long-term bone marrow cultures
      (LTBMC) of human bone marrow cells to investigate the effect of HIV-1 on in vitro
      hematopoiesis. Confluent stromal cell layers established from human bone marrow
      cells were irradiated to eliminate residual hematopoietic progenitor cells and
      exposed to HIV-1ADA or to HIV-1IIIB, monocytotropic and lymphocytotropic strains
      of HIV-1, respectively. A productive infection did not develop in cultures
      exposed to HIV-1IIIB but did for cultures exposed to HIV-1ADA as there was a
      progressive increase in HIV-1 p24 antigen. Stromal cell layers infected with HIV
      1ADA were also cocultured with autologous CD34+ bone marrow cells. Four days, 1,
      2, and 3 weeks later, the number of colony-forming units granulocyte/macrophage
      (CFU-GM) in non- and HIV-infected LTBMC was determined. The number of CFU-GM
      increased during the first week in both non- and HIV-infected LTBMC. One week
      after the coculture of CD34+ cells with stromal cell layers infected with HIV
      1ADA, the number of CFU-GM in six out of eight experiments was reduced compared
      to noninfected control LTBMC. In those six experiments, the number of CFU-GM was
      53 +/- 6% standard error of the mean (SEM) of the number in noninfected LTBMC. A
      reduced number of CFU-GM was observed in the nonadherent fraction of HIV-infected
      LTBMC for at least 2 weeks. These results demonstrate that some cells in the
      stromal cell layers of LTBMC were targets for HIV-1 and that HIV-infected stromal
      cell layers suppressed or delayed the production of CFU-GM.

PMID- 7525332
TI  - Laser effects on myelinated and nonmyelinated fibers in the rat peroneal nerve: a
      quantitative ultrastructural analysis.
AB  - We have recently shown that Nd:YAG laser irradiation of rat peripheral nerve
      differentially impairs action potential transmission in small, slowly conducting
      sensory fibers compared to fast conducting afferents. In addition, the number of
      small sensory neurons of the A-delta- and C-fiber group labeled with HRP is
      significantly reduced after laser irradiation, while the number of labeled large
      sensory neurons and motoneurons was not affected. To further evaluate this laser
      induced injury, we examined three distinct regions of the laser-irradiated rat
      peroneal nerve using ultrastructural morphometric methods. These regions were the
      site of laser irradiation and zones 10 mm proximal and 5 mm distal to the injury.
      The contralateral nerve was sham treated. Our results indicate that for the small
      nonmyelinated fibers, there was a significant increase in both mean fiber size
      and the number of microtubules per fiber, but a decrease in the number of
      neurofilaments. In contrast, the number of myelinated and nonmyelinated fibers is
      not significantly altered at 7 days following laser irradiation, and the mean
      diameter and frequency distribution of myelinated nerve fibers was unchanged.
      This study demonstrates that selective functional alterations in laser-irradiated
      nerves (nerve conduction velocity, HRP transport properties) are accompanied by
      ultrastructural changes of axonal organelles in nonmyelinated fibers. Nd:YAG
      laser light might ultimately prove to be a powerful tool to selectively alter
      functional properties in small, slowly conducting afferent fibers, without
      causing degeneration at the ultrastructural level at the site of irradiation. We
      hypothesize further that the laser-induced functional alterations might be
      related to differential thermally mediated changes.

PMID- 7525331
TI  - Systemic or local administration of azide produces striatal lesions by an energy
      impairment-induced excitotoxic mechanism.
AB  - Sodium azide is an inhibitor of cytochrome oxidase which produces selective
      striatal lesions in both rodents and primates. In the present study we
      investigated the neurochemical and histologic effects of both intrastriatal and
      systemic administration of sodium azide, as well as the age dependence and
      mechanism of the lesions. Intrastriatal administration of sodium azide produced
      dose-dependent lesions. Neurochemical and histologic evaluation showed that
      markers of both spiny projection neurons (GABA, substance P) and aspiny
      interneurons (somatostatin, neuropeptide Y, NADPH-diaphorase) were equally
      affected. Subacute systemic administration of sodium azide resulted in lesions
      with a similar neurochemical profile; however, in contrast to intrastriatal
      injections there was sparing of dopaminergic striatal afferents. Prior
      decortication significantly attenuated lesions produced by intrastriatal
      administration of sodium azide, consistent with an excitotoxic process. Chronic
      administration of sodium azide for 1 month lead to striatal neuropathological
      changes. Lesions produced by intrastriatal administration of sodium azide in 1-,
      4-, and 12-month-old animals showed age dependence. Both freeze-clamp
      measurements and chemical-shift magnetic resonance spectroscopy confirmed that
      sodium azide impairs oxidative phosphorylation in the striatum following either
      intrastriatal or systemic administration. These results show that the striatum is
      particularly vulnerable to oxidative stress produced by sodium azide, and that it
      produces striatal lesions by a secondary excitotoxic mechanism.

PMID- 7525333
TI  - Rostral reticular nucleus of the thalamus sends a patchy projection to the
      pulvinar lateralis-posterior complex of the cat.
AB  - The pulvinar lateralis posterior complex (Pul-LP) and the reticular nucleus of
      the thalamus (RE) are thought to be involved in visual and attention-related
      tasks. This report provides data on the anatomical connections between these two
      nuclei following the analysis of injections of horseradish peroxidase (HRP) +
      [3H]leucine into the Pul-LP and RE of the cat. Following the retrograde transport
      of HRP from the Pul-LP, labeled cells were distributed in regions of the RE
      ventral to the caudate nucleus and adjacent to the stria terminalis between
      Horsley-Clarke anterior-posterior (AP) coordinates 13.0 and 9.5 and more caudally
      in areas dorsal and ventral to the lateral geniculate nucleus (LGN) between AP
      9.0 and 4.5. The majority of the cell labeling within the RE following injections
      within the Pul-LP was seen dorsal to the lateral geniculate nucleus around AP 6.5
      6.0. Cell labeling was heaviest following injections within the lateral LP in
      contrast to injections within the Pul which resulted in fewer labeled cells.
      Autoradiographic analysis of the anterograde transport of leucine showed that the
      labeled Pul-LP fibers within the RE did not completely coincide with the
      distribution of HRP-labeled reticular cells from the same injection site. This
      indicated a lack of strict reciprocity between these two nuclei. In addition,
      injections of [3H]leucine into dorsomedial areas of the RE near the rostral pole
      of the LGN resulted in a patchy distribution of label within the Pul-LP which was
      most prominent as oblique dorsoventral slabs across the thalamus. It was inferred
      that this distribution was along the borders between different subdivisions
      within the Pul-LP. The lack of strict reciprocity between the thalamic relay
      nuclei and the reticular nucleus implies that areas of the Pul-LP may receive
      inhibition from RE regions which they do not directly influence; this anatomical
      feature may provide a basis for selective inhibition of thalamic nuclei.

PMID- 7525334
TI  - The distribution of inflammatory demyelinated lesions in the central nervous
      system of rats with antibody-augmented demyelinating experimental allergic
      encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) has long been studied as an animal
      model of the human demyelinating disease Multiple Sclerosis. However, EAE induced
      in the Lewis rat by injection of myelin basic protein (MBP), or MBP-specific T
      lymphocytes, is primarily an inflammatory condition of the central nervous system
      (CNS) with little or no demyelination. In EAE models in which demyelination does
      result, it is either not very widespread or is unpredictable in its degree and
      location. In this study we have produced antibody-augmented demyelinating EAE
      (ADEAE) in the Lewis rat by injection of activated MBP-specific T-lymphoblasts,
      followed by injection 4 days later of a monoclonal antibody against
      myelin/oligodendrocyte glycoprotein, an extrinsic protein of myelin. We have
      documented the extent and location of inflammatory cell infiltrates and
      demyelination throughout the CNS using histochemistry, immunofluorescence, and
      image analysis. Perivascular inflammatory infiltrates were seen in the deep
      cerebellar white matter and in the folia. Perivascular, periventricular, and
      subpial inflammation was widespread throughout the pons/medulla and at all levels
      of the spinal cord. Very little inflammation was apparent in the forebrain. MBP
      immunofluorescence demonstrated extensive areas of periventricular demyelination
      in the forebrain around the third ventricle. Both periventricular and
      perivascular lesions were commonly observed in the cerebellum and pons/medulla.
      The extent of demyelination in the spinal cord increased caudally with large
      confluent areas of subpial demyelination seen throughout the lumbar cord. The
      extensive and reproducible distribution of inflammatory demyelinating lesions in
      ADEAE provide the possibility to select areas of the CNS for more detailed
      analysis of the cellular changes that accompany demyelination and remyelination.

PMID- 7525335
TI  - Implantation of PNS graft inhibits the induction of neuronal nitric oxide
      synthase and enhances the survival of spinal motoneurons following root avulsion.
AB  - In a spinal root injury model, our previous studies have shown that induction of
      nitric oxide synthase (NOS) appears only in spinal motoneurons of the root
      avulsed segment in which significant motoneuron loss occurs but not in those of
      the distal root-axotomized segment (root axotomy 5-10 mm from the spinal cord) in
      which most motoneurons survive the injury. One hypothesis for the different
      response of motoneurons to root avulsion and distal root axotomy is that
      neurotrophic factors produced by the remaining peripheral nervous system (PNS)
      component are available for the distally axotomized motoneurons but are not
      available following avulsion. This hypothesis is tested in the present study by
      implantation of a PNS graft following the root avulsion. Results of the present
      study show that implantation of a PNS graft significantly enhances the survival
      of motoneurons following avulsion. Expression of NOS due to avulsion injury is
      completely inhibited in all motoneurons that regrow into the PNS graft. These
      results indicate that induction of NOS in avulsed motoneurons may result from the
      deprivation of neurotrophic factors produced by the PNS component, and the
      survival promoting effects of neurotrophic factors may be achieved by modifying
      certain cellular molecules such as NOS.

PMID- 7525336
TI  - Giardia lamblia: traffic of a trophozoite variant surface protein and a major
      cyst wall epitope during growth, encystation, and antigenic switching.
AB  - Both trophozoites and cysts of Giardia lamblia have unique outer surfaces that
      protect them from very different hostile environments. However, little is known
      about the transport of these important molecules to the cell surface. We used
      monospecific anti-recombinant TSA 417 antibodies and mAb 8C5 in double label
      immunoelectron microscopy to compare the localization and transport of this major
      trophozoite surface antigen (TSA) with that of a prominent cyst wall epitope
      during vegetative growth, encystation, and antigenic switching in vitro. TSA 417
      is a marker of the constitutive transport of the major plasma membrane protein,
      while the 8C5 epitope traces a differentiation-regulated secretory pathway to the
      cyst wall. Both proteins localized to the nuclear envelope endoplasmic reticulum
      (ER) cisternae, ER, and cytoplasmic membrane cisternae, reflecting their site of
      synthesis, but only the differentiation-specific epitope 8C5 localized to the
      encystation-specific vesicles (ESV). These large secretory vesicles form only
      during encystation and transport cyst antigens to the nascent wall. In contrast,
      only TSA 417 was found on the outer surface of the plasmalemma of trophozoites
      and encysting cells and underlaying the walls of many cysts, while only 8C5
      localized to the cyst wall. As encystation progressed, TSA 417 disappeared from
      the plasmalemma and increased in the lysosome-like PV and other large cytoplasmic
      vesicles. In contrast to their segregation in the ESV and on the cell surface,
      both TSA 417 and 8C5 were found in the peripheral vesicles, presumably an
      endocytic compartment. We propose that this may be the initiation of a stage in
      differentiation-driven antigenic switching of TSA 417, in which this antigen is
      no longer synthesized or exported to the plasmalemma, but is taken back inside
      the cell.

PMID- 7525337
TI  - Toxoplasma gondii: a monoclonal antibody that inhibits intracellular replication.
AB  - During its intracellular life cycle within the infected host cell, Toxoplasma
      gondii is able to undergo rapid asexual replication. Neither the mechanism by
      which the parasite initiates this process nor the requirements for maintaining it
      are understood. We produced a monoclonal antibody, 1B8, that identifies a
      parasite antigen of approximate M(r) 97 kDa as determined by SDS-PAGE. The
      epitope recognized by mAb 1B8 appears as a collection of vesicular structures
      scattered throughout the cell cytoplasm. When RH strain parasites are incubated
      with mAb 1B8 in the absence of serum complement, parasite growth is inhibited by
      > 90% as determined by radioisotope incorporation. Both attachment and invasion
      assays show that neither of these parasite-host cell interactions are inhibited
      by the mAb. However, a marked reduction in the number of intracellular rosettes
      was observed following mAb treatment of the parasites. Viable extracellular
      parasites are able to endocytose mAb 1B8. Once within the parasite cytosol the
      antibody recognizes the vesicular structures similar to those observed with fixed
      parasites. Immunofluorescence assays with Besnoitia jellisoni and Plasmodium
      falciparum show that the epitope recognized by mAb 1B8 is conserved among
      Coccidiae but not the kinetoplastid Leishmania.

PMID- 7525339
TI  - Characterization of extreme apical antigens from Toxoplasma gondii.
AB  - We have isolated 26 monoclonal antibodies which specifically recognize the
      extreme apex of Toxoplasma gondii, a protozoan parasite which attaches to and
      invades host cells via its specialized apical end. The unique apical organelles
      which define the phylum Apicomplexa are thought to be involved in mechanical and
      enzymatic aspects of invasion. Immunoblots, immunofluorescence morphology, and
      immunogold labeling define six classes of apically localized antigens recognized
      by these antibodies. Three of the classes are detergent-insoluble and localize to
      the conoid and the cytoplasmic face of the apical membrane, suggesting that they
      may be part of the parasite's membrane cytoskeleton. The remaining three classes
      extract with detergent and are associated with internal membrane bounded vesicles
      (micronemes and the upper necks of rhoptries). One class of micronemal antigens
      appears to be cell cycle regulated. This antigen localizes to the cytoplasm,
      especially the perinuclear region, in thin (recently replicated) parasites, but
      is apical in larger parasites.

PMID- 7525340
TI  - Potentiation of gentamicin nephrotoxicity in the rat by infusion of aprotinin.
AB  - The present study was undertaken to examine a possible effect of aprotinin, a 6.5
      kDa polypeptide with an inhibitory effect on proteolysis, on aminoglycoside
      nephrotoxicity. Experimental animals (female Sprague-Dawley rats, 175-200 g body
      wt) were treated for 4 days with 40 mg/kg gentamicin given ip at 12-hr intervals.
      Aprotinin (40,000 kIU per animal) was infused i.v. over a period of 8 days, using
      subcutaneously implanted miniosmotic pumps. In protocol A, infusion pumps were
      placed 4 days before starting gentamicin treatment. In protocol B, pumps were
      implanted 15-18 hr prior to first gentamicin administration. In addition to rats
      exposed to both gentamicin and aprotinin (GAP), animals were treated with
      gentamicin ip+saline i.v. (G), saline ip+aprotinin i.v. (AP), or received only
      saline by both routes of administration (C). All rats were terminated 4 days
      after the end of gentamicin dosing. One hour before sacrifice, 200 microCi of
      [3H]thymidine was given ip to each animal in order to monitor cell turnover in
      renal tissue. The kidneys were analyzed with respect to (i) histopathological
      alterations and renal dysfunction, (ii) aminoglycoside tissue accumulation, and
      (iii) tubular regeneration (measurement of cell proliferation). In animals
      receiving aprotinin alone, histological examination of renal cortex on paraffin
      sections disclosed mild tubular injury with focal cell necrosis. In plastic
      embedded tissue, proximal tubule epithelium was characterized by the presence of
      numerous inclusions densely stained with toluidine blue. At the ultrastructural
      level, these inclusions appeared filled with amorphous electron-dense material.
      In gentamicin-treated animals, cortical drug accumulation reached values higher
      than 0.3 mg/g renal tissue, but a significant 30-40% decrease of gentamicin
      accumulation was noted in GAP groups, compared to G groups. Histological
      examination of renal cortex (paraffin sections) revealed the development of acute
      tubular necrosis in both G and GAP groups. Tubular injury was accompanied by mild
      renal dysfunction, as shown by the level of serum creatinine which was increased
      almost 3-fold in the G group, compared to C and AP groups. Aprotinin infusion
      produced a further increase of serum creatinine, particularly in protocol A where
      it was 72% higher for the GAP group than for the G group. In both G and GAP
      groups, postnecrotic tubular regeneration was evidenced by determining the rate
      of DNA synthesis and the frequency of S-phase cells in renal cortex. Both methods
      gave consistent results and showed a 8- to 13-fold increase of cell proliferation
      in groups receiving gentamicin alone, compared to C groups.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7525341
TI  - Molecular epidemiology of Salmonella enteritidis.
AB  - Sixteen strains of Salmonella enteritidis isolated in 1991 from 13 unrelated
      poultry-associated sources, 7 strains from 2 community outbreaks, and 18 human
      sporadic isolates were investigated by phage typing, analysis of rRNA gene
      restriction patterns (ribotyping) and plasmid profiles. Four different phage
      types and 10 SphI patterns were found, whereas plasmids were identical in all but
      4 isolates. Only one ribotype (RT A) occurred among both human and avian strains.
      This particular ribotype was also responsible for the two outbreaks investigated,
      suggesting that such strains may be of special significance for the increase of
      S. enteritidis infections.

PMID- 7525338
TI  - Ultrastructural localization of CD36 in human hepatic sinusoidal lining cells,
      hepatocytes, human hepatoma (HepG2-A16) cells, and C32 amelanotic melanoma cells.
AB  - Ultrastructural localization of CD36 in human hepatic sinusoidal lining cells,
      hepatocytes, human hepatoma (HepG2-A16) cells, and C32 amelanotic melanoma cells.
      Experimental Parasitology 79, 383-390. CD36 is expressed in the endothelial cells
      of some human organs, but the ultrastructural localization of this molecule in
      the sinusoidal lining cells of human liver is not well established. We report the
      ultrastructural localization of CD36 in the liver using a novel murine monoclonal
      antibody against CD36, namely MO30, as a primary antibody. Immunocytochemistry by
      the postembedding method showed that CD36 was localized in endothelial cells of
      sinusoids and in hepatocyte microvilli protruding into the space of Disse.
      Moreover, in cultured human hepatoma (HepG2-A16) cells and C32 amelanotic
      melanoma cells, MO30 reacted with microvilli. Hence, CD36 expressed on these
      cells may be involved in recognition and/or entry of these cells by malaria
      sporozoites.

PMID- 7525342
TI  - Foetal airway motor tone in prenatal lung development of the pig.
AB  - The terminal airways from embryonic lung in situ or as explants exhibit rhythmic
      spontaneous contractions. Our objective was to see whether narrowing responses of
      the airways occurred throughout the bronchial tree in the first trimester foetus
      and, if so, to characterize them. The bronchial tree was freed of vasculature and
      parenchyma from the lungs of 20-35 g pig foetuses (44-48 days gestation). The
      airway lumen was visualized directly with transmitted light, and narrowing was
      recorded in real time by video-imaging microscopy. From the main stem bronchi to
      the terminal regions of late generation branches (20-35 microns i.d.) strong
      bronchoconstrictor responses to micromolar concentrations of acetylcholine (ACh),
      histamine, substance P and K+ depolarizing solution were seen, whilst inhibition
      of narrowing with beta-adrenoceptor agonists was evidence of beta-receptors on
      the smooth muscle. Moreover, strong narrowing responses to electrical field
      stimulation, which were blocked by atropine, indicated that functional
      cholinergic nerves were present. A remarkable display of spontaneous narrowing in
      the airways of many of the bronchial tree preparations caused the movement of
      lung liquid to and fro. We speculate that the bronchomotor tone and associated
      spontaneous activity, which move the lung fluid along the airways, serve to
      maintain an even positive pressure in localized areas of the bronchial tree which
      is essential to provide the stimulus for continued growth of the lung.

PMID- 7525343
TI  - The expression of intercellular adhesion molecule-1 and the beta 1-integrins in
      asthma.
AB  - Expression of intercellular adhesion molecule-1 (ICAM-1) appears to be important
      to the development of bronchial hyperresponsiveness and eosinophilia in Ascaris
      sensitized monkeys. Beta 1-integrins are expressed on epithelial cells, and may
      contribute to adherence of epithelial cells to the basement membrane. The aim of
      this study was to determine whether adhesion receptor expression was altered in
      human asthmatic bronchial epithelium. Using monoclonal antibody staining, we have
      examined the expression of ICAM-1 and the alpha 1-alpha 6-subunits of the beta 1
      integrin family in bronchial mucosal biopsies from 33 asthmatic and 13
      nonasthmatic subjects. The epithelium was positive for ICAM-1 in 26 out of 33
      asthmatics, although negative in all 13 nonasthmatics. ICAM-1 expression was not
      associated with bronchial responsiveness or with medication requirements. Beta 1
      integrin staining showed that alpha 2-, alpha 3- and alpha 6-subunits stained the
      epithelium in all cases. Alpha 4 staining was weakly positive in the epithelium
      in five asthmatics. Alpha 5 staining was weak in asthmatics and normals. Alpha 4
      and alpha 6-subunits also stained inflammatory cells. Epithelial upregulation of
      ICAM-1 is present in asthma. Beta 1-integrins with alpha 2-, alpha 3- and alpha 6
      subunits appear to be constitutively expressed in bronchial epithelium.

PMID- 7525344
TI  - Nasal eosinophilia induced by PAF-acether is accompanied by the release of
      eosinophil cationic protein.
AB  - It has been demonstrated that platelet-activating factor (PAF)-acether can induce
      nasal neutrophilia and eosinophilia, with a different degree of responsiveness in
      atopic and in nonatopic subjects. The aim of this study was to evaluate whether
      PAF can also induce the release of secondary mediators in the human nose. Ten
      patients with allergic rhinitis and 10 normal subjects underwent nasal challenge
      with PAF (500 nmol), lyso-PAF (500 nmol) and saline solution. Nasal lavages were
      performed before and after challenge to evaluate changes in nasal cytology and
      release of histamine, immunoreactive leukotriene (iLT) C4 and eosinophil cationic
      protein (ECP). PAF caused neutrophilia and eosinophilia, which appeared earlier
      in atopic than in nonatopic subjects (30 min vs 1 h), and peaked 3 h after
      challenge in both groups. Lyso-PAF caused mild neutrophilia, which appeared 3 h
      after challenge in both groups; an increase in eosinophil counts was observed 3 h
      after challenge in atopic subjects, but not in nonatopic subjects. PAF
      insufflation caused a significant release of ECP in nasal lavage fluids 30 min
      and 3 h after challenge in atopic subjects, and 3 h after challenge in nonatopic
      subjects. ECP levels in the nasal lavages collected 30 min and 3 h after
      challenge with PAF were higher in atopic than in nonatopic subjects. Eosinophil
      counts correlated with ECP levels in the nasal lavages collected 30 min after PAF
      challenge in atopic subjects. Nasal challenge with lyso-PAF did not provoke any
      release of ECP. No significant increase of histamine and iLTC4 levels in nasal
      lavages was found after challenge with either PAF or lyso-PAF.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7525345
TI  - Equivalent regulation of wild type and an epitope-tagged variant of Gs alpha by
      the IP prostanoid receptor following expression in neuroblastoma x glioma hybrid,
      NG108-15, cells.
AB  - NG108-15 cells were transfected to stably express a haemagglutinin epitope-tagged
      variant of the long isoform of Gs alpha. Clone BST15 expressed this polypeptide
      at similar levels to the endogenous long isoform of Gs alpha. Treatment of clone
      BST15 with the IP prostanoid receptor agonist iloprost resulted in down
      regulation of both forms of Gs alpha with both dose-effect curves to iloprost and
      time courses of loss of the two forms of Gs alpha being indistinguishable. These
      results demonstrate that the IP prostanoid receptor interacts with and regulates
      the epitope-tagged variant of Gs alpha in an equivalent manner to the unmodified
      protein and indicates that the epitope-tagged polypeptide can be used to analyse
      mechanisms of receptor regulation of cellular G-protein levels.

PMID- 7525347
TI  - Sequence-specific hypomethylation of the tobacco genome induced with
      dihydroxypropyladenine, ethionine and 5-azacytidine.
AB  - Higher plant DNA is methylated at CG and CNG targets. In this study we have
      investigated the tobacco methylation system in tissue culture using the
      methylation inhibitors 5-azacytidine (5-azaC), dihydroxypropyladenine (DHPA) and
      ethionine (Ethi), and methylation-sensitive restriction endonucleases HpaII,
      MspI, HhaI, EcoRII, ScrFI, and Fnu4HI. Surprisingly, CAG/CTG sequences, contrary
      to CG doublets and CCG/CGG triplets, appeared to be refractory to the inhibitory
      effect of 5-azaC. Thus 5-azaC cannot be considered a general inhibitor of DNA
      methylation in tobacco cells. On the other hand, DHPA, the inhibitor of S
      adenosylhomocysteine (SAH) hydrolase, and Ethi caused hypomethylation of both
      CAG/CTG and CCG/CGG triplets but not of the CG doublets. The sensitivity of
      triplet-specific methylation to the inhibition of SAH hydrolase suggests the
      possibility that plant-specific DNA methylation at CNG targets might be modulated
      by alterations of the SAH/S-Adenosylmethionine ratio in plant cells.

PMID- 7525348
TI  - Expression of type II thyroxine 5'-deiodinase from rat harderian gland in Xenopus
      laevis oocytes.
AB  - The presence of isoenzymes mediating the conversion of thyroxine to 3,5,3'
      triiodothyronine has been studied according to characteristic kinetics and
      physiological regulation. In this paper, we report the expression of type II 5'
      deiodinase (5'D) activity in oocytes of Xenopus laevis. Oocytes injected with
      total RNA extracted from rat Harderian gland, and then incubated up to five days
      demonstrated a progressive increase in 5'D activity, reaching a maximal value at
      24 h; then, 5'D activity remained almost stable for an additional period of four
      days. Characteristics of the enzyme activity expressed by oocytes included its
      inhibition by iopanoic acid, but not by propylthiouracil, and its increase during
      beta-adrenergic agonist treatment and hypothyroidism. The expressed activity
      manifests characteristics typical of the type II isoenzyme. Deiodinating activity
      in oocytes also exhibited diurnal variations. In this study, 5'D activity
      expressed in oocytes exhibited low values when animals were killed during the
      day, and high values when animals were killed at night. Maximal values were
      reached 3-4 h before the nocturnal peak of 5'D activity in Harderian gland crude
      homogenates. Results suggest that the in vivo activation of 5'D by isoproterenol,
      hypothyroidism, or dark exposure may be caused by an increase in the synthesis
      and/or maturation of the RNA expressing the enzyme.

PMID- 7525346
TI  - Stable expression of VLA-4 and increased maturation of the beta 1-integrin
      precursor after transfection of CHO cells with alpha 4m cDNA.
AB  - A full-length cDNA coding for the murine alpha 4 integrin subunit (alpha 4m) was
      transfected into CHO-K1 cells and cell lines that expressed VLA-4 at their
      surface as a result of the association of transfected alpha 4m with endogenous
      hamster beta 1 were selected. Functionality of the expressed alpha 4m beta 1 was
      shown by adhesion assays on VCAM-1 and antibody (anti-VCAM-1) inhibition. Pulse
      chase experiments indicated that transfection of the murine alpha 4 cDNA into CHO
      cells led to an increase in maturation and a decrease in degradation of the beta
      1 precursor subunit compared to control CHO-K1 cells. This was supported by FACS
      analysis, using an anti-hamster beta 1 monoclonal antibody, which showed that
      more beta 1 subunit was expressed at the surface of these stably transfected
      alpha 4m expressing cells. These results support the hypothesis that degradation
      of precursor beta 1 is at least partly determined by the quantity of alpha
      subunits available intracellulary for heterodimer formation.

PMID- 7525349
TI  - Processing and secretion of rat alpha 1-microglobulin-bikunin expressed in
      eukaryotic cell lines.
AB  - The precursor protein alpha 1-microglobulin-bikunin was cleaved to the same
      degree whether expressed in CHO cells or in mutated CHO cells, RPE.40 cells,
      suggested to lack a functional form of the intracellular protease furin. Thus,
      alpha 1-microglobulin-bikunin probably is not cleaved in vivo by furin. However,
      simultaneous overexpression of the precursor and furin in COS, CHO and RPE.40
      cells increased the cleavage, suggesting that compartmentalisation and
      concentrations of protease and precursor are important for the cleavage, besides
      the in vitro specificity. Expression of alpha 1-microglobulin and bikunin alone
      gave different protein patterns of SDS-PAGE as compared to expression of the
      precursor and subsequent cleavage, suggesting that the precursor protein is
      important for the post-translational handling of alpha 1-microglobulin and
      bikunin.

PMID- 7525350
TI  - RNA/DNA hybrid duplexes with identical nearest-neighbor base-pairs have identical
      stability.
AB  - Energetic behaviors of eight pairs of RNA/DNA hybrid duplexes with identical
      nearest neighbors have been investigated by UV melting analysis. In the pairs
      with identical nearest-neighbor pairs, the melting curve traces at the same
      strand concentration were very similar. The average difference in stabilization
      energy of these pairs was 4%, which was about expected within experimental error.
      These results indicate that the nearest-neighbor model is valid for predicting
      the stability of RNA/DNA hybrid duplexes as well as RNA/RNA and DNA/DNA duplexes.

PMID- 7525351
TI  - Pore-forming peptide of Entamoeba histolytica. Significance of positively charged
      amino acid residues for its mode of action.
AB  - Amoebapore is a 77-residue pore-forming peptide from Entamoeba histolytica with
      antibacterial and cytolytic properties. It contains eight lysine residues and one
      histidine residue. Chemical modifications of amoebapore with various reagents
      affecting either both types of cationic residues or lysine and histidine residues
      separately resulted in virtually complete loss of pore-forming activity. The
      activity was restored by reversal of modifications. Whereas amoebapore was no
      longer capable of binding to phospholipid vesicles when its lysine residues were
      modified, the modification of the single histidine primarily affected
      oligomerization of the peptide upon membrane association.

PMID- 7525352
TI  - PVP-containing solutions for analysis of divalent cation-dependent NMDA responses
      in Xenopus oocytes.
AB  - The electrophysiological analysis of Ca(2+)-conducting ion channels in Xenopus
      oocytes is difficult due to secondary intracellular effects induced by Ca2+. In
      the presence of polyvinylpyrrolidone (PVP) membrane currents can be recorded in
      nominally divalent cation-free solutions. The Ca(2+)-permeable recombinant NMDA
      receptors of the NR1/NR2A subtype were used as assay system and the results show
      that PVP has no effect on NMDA receptor-induced currents. Ca2+ and Ba2+ depress
      NMDA-induced currents at submillimolar concentrations probably by interfering
      with the Na+/K+ flux. This block is fully reversible as also observed for Mg2+
      but shows in contrast no pronounced voltage dependence. PVP-containing solutions
      may be useful for the analysis of divalent cation-dependent ion channels.

PMID- 7525353
TI  - Selectivity of DNA polymerases toward alpha and beta nucleotide substrates of D
      and L series.
AB  - The substrate properties of four carbocyclic D and L nucleoside 5'-triphosphate
      analogs toward HIV and AMV reverse transcriptases and terminal deoxynucleotidyl
      transferase were evaluated. The compounds of the D-beta and L-beta series were
      found to be terminating substrates for these enzymes, while the derivatives of
      the D-alpha and L-alpha series were recognized only by terminal deoxynucleotidyl
      transferase, suggesting that for the template-independent enzyme the mutual
      orientation of the two fragments is of no significance. A hypothesis for binding
      of nucleotides to the DNA polymerase active center was proposed.

PMID- 7525355
TI  - Kinetic analyses of DNA-linked ribonucleases H with different sizes of DNA.
AB  - A series of DNA-linked ribonucleases H with DNA adducts varying in size and
      sequence, ranging from heptamer to nonamer, were constructed and examined for
      their ability to cleave the 12-base RNA (5'-CGGAGAUGACGG-3') site-specifically.
      The DNA-linked RNase H with the 9-base DNA (5'-GTCATCTCC-3') cleaved the 12-base
      RNA specifically at A6-U7. Kinetic studies revealed that the DNA-linked RNase H
      with the 8-base DNA (5'-TCATCTCC-3') cleaved it slightly more effectively than
      that with the 9-base DNA. Factors that may affect the specificity and catalytic
      efficiency of a DNA-linked RNase H are described.

PMID- 7525356
TI  - Enhancing effect of the 3'-untranslated region of tobacco mosaic virus RNA on
      protein synthesis in vitro.
AB  - In order to test the enhancing effect of the 3'-terminal untranslated region (3'
      UTR) of tobacco mosaic virus (TMV) RNA on protein synthesis in vitro we used a
      chimeric mRNA construct containing TMV 5'-UTR (omega) and firefly luciferase
      mRNA. The addition of the TMV 3'-UTR to the chimeric mRNA construct results in a
      more than 3-fold stimulation of the synthesis of the functionally active protein
      in the wheat germ cell-free translation system. We have demonstrated that the
      proper length of the TMV 3'-terminal part is important for efficient translation;
      elongation of the TMV tail by 160 vector-derived nucleotides fully abolishes the
      stimulation effect of the TMV 3'-UTR in vitro.

PMID- 7525354
TI  - Affinity modification of human immunodeficiency virus reverse transcriptase and
      DNA template by photoreactive dCTP analogs.
AB  - New base-substituted analogs of dCTP containing an azido group have been
      synthesized and applied to a selective photoaffinity modification of HIV-RT
      (p66/p51 heterodimer). The labeling of only the 66 kDa subunit of HIV-RT was
      detected when the enzyme was first irradiated with the analogs and then template
      (5'-(d)GGTTAAATAAAATAGTAAGAATGTATAGCCCCTACCA-3') and 5' 32P end-labeled 3'
      (d)TTACATATCGGGGATGGT-5' primer were added. The 5' 32P end-labeled primer
      elongated by dCTP analogs in the presence of both HIV-RT and DNA template is able
      to modify both subunits of HIV-RT and DNA template. This way of specific cross
      linking to both DNA (RNA) template and HIV-RT opens up new possibilities to study
      the HIV-RT active site.

PMID- 7525357
TI  - Botulinum C3 exoenzyme blocks the tyrosine phosphorylation of p125FAK and
      paxillin induced by bombesin and endothelin.
AB  - In this study we examined the role of rho p21 in neuropeptide-stimulated tyrosine
      phosphorylation. Intact Swiss 3T3 cells were treated with the Clostridium
      botulinum C3 exoenzyme which specifically ADP ribosylates and inactivates rho
      p21. C3 exoenzyme treatment of cells caused a marked decrease in both bombesin-
      and endothelin-stimulated tyrosine phosphorylation of multiple proteins,
      including p125 focal adhesion kinase (FAK) and paxillin. Our results suggest that
      rho p21 is a component of the signal transduction pathway linking seven
      transmembrane domain receptors with tyrosine phosphorylation and cytoskeletal
      events.

PMID- 7525358
TI  - p53 expression in nitric oxide-induced apoptosis.
AB  - Nitric oxide (NO) is a diffusible messenger involved in several patho
      physiological processes including immune-mediated cytotoxicity and neural cell
      killing. NO or the products of its redox chemistry can cause DNA damage and
      activate subsequent lethal reactions including energy depletion and cell
      necrosis. However, regardless of whether it is endogenously produced in response
      to cytokines, or generated by chemical breakdown of donor molecules, NO can also
      induce apoptosis in different systems. Here, we report that NO generation in
      response to a cytokine induced NO-synthase or by NO donors stimulates the
      expression of the tumor suppressor gene, p53, in RAW 264.7 macrophages or
      pancreatic RINm5F cells prior to apoptosis. NO-synthase inhibitors such as NG
      monomethyl-L-arginine prevent the inducible NO generation as well as p53
      expression and apoptosis. Since p53 expression is linked to apoptosis in some
      cells exposed to DNA damaging agents, we suggest that NO-induced apoptosis in
      these cell systems is the consequence of DNA damage and subsequent expression of
      this tumor suppressor gene.

PMID- 7525359
TI  - Very low dose danazol for relief of endometriosis-associated pelvic pain: a pilot
      study.
AB  - OBJECTIVES: To evaluate the efficacy and safety of very low dose danazol in
      improving pelvic pain in women with endometriosis, the benefit of preceding the
      treatment by a short course of a GnRH agonist, symptoms recurrence after drug
      withdrawal, and variations in menstrual pattern. DESIGN: Open-label, randomized
      study. SETTING: University hospital endometriosis center. PATIENTS: Forty-two
      women with moderate or severe pelvic pain and laparoscopically diagnosed
      endometriosis. INTERVENTIONS: Treatment with oral danazol, 50 mg/d, for 9 months
      (group I, n = 21) or leuprolide depot for 3 months followed by oral danazol, 50
      mg/d, for 6 months (group II, n = 21), and a 6-month follow-up. MAIN OUTCOME
      MEASURES: Variations in severity of symptoms during treatment and at the end of
      follow-up as shown by a linear analog scale and a verbal rating scale; menstrual
      blood loss as assessed by a pictorial chart. RESULTS: Four patients withdrew from
      the study, one in each group at the fifth month of treatment (for persistent
      pain) and one in each group during follow-up (they requested additional therapy);
      one woman in group I was lost to follow-up. Significant improvements were
      obtained in dysmenorrhea, deep dyspareunia, and nonmenstrual pain in both
      treatment schedules without differences between the groups. Also menstrual blood
      loss was significantly reduced in both groups. A temporary fall in high and rise
      in low density lipoprotein cholesterol was observed in the study population. At
      the end of follow-up symptoms recurred without significant differences in median
      pain scores with respect to baseline. CONCLUSION: Very low dose danazol may be an
      alternative for temporary relief of endometriosis-associated pain. Ovulation is
      not always inhibited and barrier contraception is needed. Side effects occur but
      are rarely severe. Further data are required to evaluate the influence of long
      term administration on the lipid profile.

PMID- 7525361
TI  - Development, repair and regeneration of the retinal pigment epithelium.
AB  - An overview is presented of the retinal pigment epithelium (RPE) cell in repair
      and regeneration. Changes in the RPE associated with repair activities have been
      described as metaplasia. However, evidence is presented to show that RPE cells do
      not become either fibroblasts or macrophages but merely adopt the appearance of
      these cell types in pathological conditions. The phenotypic alterations seem to
      be substrate-related. The fibroblast form predominates on two-dimensional
      substrates rich in fibronectin and in three-dimensional collagen matrices. The
      macrophage form seems to be associated with insubstantial or inadequate
      substrates such as the vitreous, photoreceptor debris and some cell surfaces. In
      altered circumstances the dedifferentiated RPE can rapidly revert to an
      epithelioid form. However, the regeneration of an effective RPE mosaic is more
      difficult and dependent on many factors including the size of the initial lesion,
      the condition of the basement area, the status of the neuroretina and the
      existing pathology in the eye. The importance for the regeneration of a normal
      functioning RPE of the cells being out of the cell cycle, establishing effective
      junctioning, reorganising their cytoskeleton and having the required adhesive
      balance with the basement membrane is emphasised.

PMID- 7525360
TI  - Follicular fluid levels of insulin-like growth factor I, insulin-like growth
      factor binding protein I, and ovarian steroids collected during ovum pick-up.
AB  - OBJECTIVE: To evaluate interrelationships between levels of insulin-like growth
      factor I (IGF-I), insulin-like growth factor binding protein (IGFBP-I), and
      ovarian steroids in late preovulatory follicular fluid (FF) after pituitary
      desensitization with GnRH agonist and controlled ovarian hyperstimulation.
      DESIGN: Follicular fluid and matched serum were collected during the ovum pick
      up. Insulin-like growth factor binding protein I, E2, P, and androstenedione (A)
      were measured by means of RIA, whereas T was measured by means of
      fluoroimmunoassay and IGF-I by means of immunoradiometric assay. SETTING:
      University teaching hospital. PARTICIPANTS: Fifty-nine patients underwent 62 ovum
      pick-ups for IVF. MAIN OUTCOME MEASURES: Levels of IGF-I, IGFBP-I, E2, P4
      (representative of follicular maturity), T, and A in FF and the volume of this
      fluid were determined. Levels of E2 to A (representative of aromatase activity)
      in FF were examined in relation to the volume of FF. RESULTS: Levels of FF-IGF-I
      decreased with increasing volume of FF. This observation is unprecedented. In
      contrast, FF-P increased with increasing volume of FF. The reverse relationships
      with FF volume between FF-IGF-I and FF-P may not be causal because no correlation
      was found between concentrations of FF-IGF-I and FF-P. Our findings are
      consistent with and complementary to those in previous reports. The follicular
      fluid E2:A ratio, FF-E2, FF-A, FF-T, and FF-IGFBP-I were not found to be
      correlated with volume of FF. CONCLUSION: Decreased levels of FF-IGF-I with
      unaltered levels of FF-IGFBP-I in larger follicles may favor a shift toward
      diminished action of IGF-I at the time of immediate preovulation. The
      physiological significance of this shift remains uncertain as it is not reflected
      in the levels of steroids in FF.

PMID- 7525362
TI  - Evolution of soft drusen in age-related macular degeneration.
AB  - The pathways by which soft drusen are formed are illustrated by representative
      clinical and clinicopathological cases. One type is derived from small hard
      drusen which first tend to aggregate into clusters and then fuse, forming larger
      deposits termed hard clusters. Breakdown of the hard drusen results in varying
      degrees of softening and confluence. These soft clusters may appear in middle age
      and, like the preceding hard drusen, remain a focal pathology. Soft clusters
      commonly lead to the atrophic form of age-related macular degeneration. Another
      type of soft drusen is formed from membranous debris as part of a diffuse
      disturbance of the retinal pigment epithelium. These membranous soft drusen first
      appear in the seventh decade and are commonly associated with choroidal
      neovascularisation.

PMID- 7525363
TI  - Different tumours, transduced with different cytokine genes as G-CSF and IL-2,
      show inhibition of tumour take through neutrophil activation but differ in T cell
      functions.
AB  - The immune effectors and the cellular mechanisms responsible for tumour rejection
      of two different tumours transduced with different cytokines have been
      characterized by immunocytochemistry and in situ hybridization. A colon (C-26)
      and a mammary (TS/A) adenocarcinoma engineered to release, respectively, 90 pg/ml
      of G-CSF (C-26/G-CSF) and 30 U or 6000 U of IL-2 (low B1.30 and high B4.6000
      level of IL-2, respectively) were compared for the type of infiltrating
      leucocytes and for the repertoire of secondary cytokines produced by the
      leucocytes recruited at the tumour site. The results indicate that in both
      systems tumour rejection is associated with prominent infiltration of CD45+/RB6
      8C5+ polymorphonuclear (PMN) leucocytes expressing mRNA for IL-1 alpha, IL-1 beta
      and TNF alpha. TS/A B1.30 and B4.6000 also showed a small proportion of
      infiltrating T lymphocytes, expressing IFN gamma and IL-4 mRNA, which were
      virtually absent in the C-26/G-CSF tumour. In mice injected with C-26/G-CSF cells
      after 600 rad irradiation, the tumours grew to about 1.5 cm and then regressed
      completely. During the regression phase, T lymphocytes were recruited within C
      26/G-CSF, and the infiltrating leucocytes were similar, in terms of
      PMN/macrophages/T lymphocytes ratio, to those found during the memory response
      elicited by injection of a challenging dose of parental TS/A into mice pre
      immunized with B1.30 IL-2-producing cells. The memory response was characterized
      by a CD4/CD8 ratio of 0.4 and by IFN-gamma and IL-4 mRNA expression, whereas the
      T lymphocytes present within regressing C-26/G-CSF were mostly CD4 (CD4/CD8 ratio
      of 2.1) and expressed IFN gamma mRNA only. The gene transfers of cytokines as
      different as G-CSF and IL-2 are able to inhibit tumour take through a similar
      anti-tumour immune response mostly due to non-specific effectors (PMN), thus
      resembling acute inflammation phenomena. Regression of C-26/G-CSF initially
      established in irradiated mice as well as rejection of TS/A tumour injected into
      B1.30 immunized mice are similar to a chronic infection but the immune reaction
      elicited by C-26/G-CSF has an impaired T-lymphocyte function.

PMID- 7525364
TI  - DNA endoreduplication, RNA and protein synthesis during growth and development of
      the antheridial basal cell in Chara vulgaris L.
AB  - Cytophotometric measurements of nuclear DNA contents and morphometric analyses
      indicate that the level of endopolyploidy plays an important role in determining
      the maximum size, transcriptional and translational activity that the antheridial
      basal cell attains during successive stages of spermatogenesis in Chara vulgaris.
      During the proliferative period of antheridial development, the metabolic
      activity of basal cell, expressed as the total incorporation of radioactive
      uridine and leucine was found to increase gradually with the increasing DNA C
      values, yet both the synthesis of RNA and then the synthesis of proteins become
      reduced at the stage preceding spermiogenesis. In accordance with some earlier
      data [2], the obtained results seem to support the hypothesis that regulatory
      mechanisms of symplasmic connections between the antheridium and a thallus
      participate in the regulation of morphogenesis of the male sex organs in Chara.

PMID- 7525365
TI  - [Clinical significance of nitric oxide in hypertension].
AB  - Vascular endothelial cells produce various biologically active factors regulating
      blood pressure, coagulation, and possibly cell growth of the vascular wall. Of
      the factors, nitric oxide (NO) has been the object of attention because of its
      quite simple molecular structure and variety of biological functions. In the
      present review, we focused on the physiologic and pathologic aspects of NO in
      hypertension. In experimental animals, both acute and chronic inhibition of NO
      synthase (NOS) with arginine derivatives produce a significant rise in blood
      pressure, indicating that tonic production of NO regulates basal vascular tonus.
      The chronic hypertension caused by NOS inhibitor is associated with cardiac
      hypertrophy and renal insufficiency. Sodium retention, though transient, and the
      plasma and tissue renin/angiotensin system in addition to the reduced production
      of NO have been implicated in the development of hypertension. Hypertension and
      the associated target organ failure can be reversed by co-administration of L
      arginine or blockades of the renin/angiotensin system. Studies in which L
      arginine as the substrate of NO or NOS inhibitor was administered demonstrated an
      important role of NO in the regulation of tonic vascular tonus also in normal
      subjects. In hypertensive subjects, however, endothelium-dependent vasorelaxation
      and production of NO are impaired, possibly due to a deficiency of L-arginine
      and/or a disorder of its utilization. Recent advances in the methods of detecting
      NO enabled us to demonstrate its diminished production from endothelial cells of
      hypertensive rats in vitro, although no definite biochemical evidence has been
      obtained in hypertensive subjects. The endothelial dysfunction, however, is not a
      primary cause of hypertension but a secondary result since it is commonly
      observed in various types of hypertension and can be reversed by correcting the
      blood pressure. Other common diseases including atherosclerosis and diabetes
      mellitus are also associated with similar abnormalities of the endothelium. NO
      has anti-atherogenic actions: inhibition of platelet functions and proliferation
      of vascular smooth muscle cells. Therefore, potentiation of endogenous NO and/or
      supplement of exogenous NO donors could be novel therapeutic approaches for the
      treatment of hypertension and atherosclerosis, while potential adverse effects of
      NO including cytotoxicity, immunosuppressibility, and hypotensive shock should be
      taken into account.

PMID- 7525366
TI  - [Granulocyte colony-stimulating factor treatment (G-CSF) of antithyroid drug
      induced granulocytopenia: granulocyte count measurement after 4 hours of G-CSF
      injection is useful for the detection of recovery from granulocytopenia].
AB  - The primary objective of this study was to ascertain the usefulness of
      granulocyte count measurement after 4 hours of granulocyte colony-stimulating
      factor (G-CSF) injections for the detection of recovery from granulocytopenia.
      Four Graves' patients with antithyroid drug-induced granulocytopenia (granulocyte
      count between 500 and 1000/mm3) and three Graves' patients with antithyroid drug
      induced agranulocytosis (granulocyte count < 500/mm3) each received a daily dose
      of 75 mu g of G-CSF administered subcutaneously. In all granulocytopenic
      patients, after 4 hours of G-CSF injection the granulocyte counts increased to
      5623, 4050, 8923 and 4647/mm3, and the granulocyte count after 24 hours of G-CSF
      injection was 3008, 4634, 4854, 4200/mm3. In one of the three agranulocytic
      patients, the granulocyte count increased from 238/mm3 to 5982/mm3 after 4 hours
      of G-CSF injection, and the granulocyte count after 24 hours of G-CSF injection
      was 4800/mm3. Although the granulocyte counts before G-CSF injection of the
      remaining two agranulocytic patients were 138 and 126/mm3, the granulocyte counts
      after 4 hours of G-CSF injection were 837 and 59/mm3 and those after 24 hours of
      G-CSF injection were 817 and 0/mm3. These results indicated that granulocyte
      count measurement after 4 hours of G-CSF injection was useful for detecting the
      recovery from granulocytopenia and agranulocytosis.

PMID- 7525367
TI  - Tubular proteins and enzyme content in the amniotic fluid.
AB  - Amniotic fluid is the product of many substances and fetal urine is considered to
      be one of the principal components. Only a few reports have been published
      describing the concentration of microglobulins and urinary enzymes in the
      amniotic fluid. We determined the levels of alpha 1-m, beta 2-m, AAP and NAG, in
      154 samples of amniotic fluid (103 early determinations and 51 late
      determinations) as a function of gestational age. We observed a statistically
      significant decrease in concentration of alpha 1-m (P < 0.001), beta 2-m (P <
      0.01) and AAP (P < 0.001) when early and late amniotic fluid samples were
      compared. A statistically significant increase of NAG (P < 0.01) and creatinine
      (P < 0.01) was also found. A significant correlation was observed between alpha 1
      m and beta 2-m, and between AAP and NAG, respectively. The potential role of
      urinary enzyme and microglobulin determination in amniotic fluid as an index of
      fetal kidney development, is discussed.

PMID- 7525368
TI  - Differential changes in gene expression in motor neurone disease.

PMID- 7525370
TI  - Subcellular localisation of AMPA receptors in rat hippocampus.

PMID- 7525371
TI  - Intestinal protein synthesis demonstrates regional sensitivity to surgical
      stress.

PMID- 7525372
TI  - The effects of thyroidectomy on intestinal protein metabolism in vivo.

PMID- 7525369
TI  - Nitric oxide synthase inhibitors attenuate the neuronal injury response in
      cerebral cortex.

PMID- 7525373
TI  - Indices of protein synthesis and RNA translating activities in the major salivary
      glands of rat and comparison to synthetic rates in liver.

PMID- 7525374
TI  - Oxidative stress induces NF kappa B DNA binding and inducible NOS mRNA in the
      human epithelial cell line A549.

PMID- 7525375
TI  - Endotoxin and steroid effects of nitric oxide synthase mRNA expression in rat
      lung and other tissues.

PMID- 7525376
TI  - Tyrosine kinase inhibitors inhibit glucose-stimulated insulin secretion.

PMID- 7525377
TI  - RNA in ventricular and atrial regions of the spontaneously hypertensive rat:
      including comparison of left ventricular protein synthesis rates with other
      models of hypertension.

PMID- 7525378
TI  - Involvement of cation channels in autoimmune disease.

PMID- 7525380
TI  - Altered expression of N-acetyl galactosamine glycoproteins by breast cancers.

PMID- 7525379
TI  - Interaction of Pseudomonas pseudomallei with macrophages.

PMID- 7525382
TI  - 3,5,3'-Triiodothyronine stimulates retinoic acid-induced differentiation in HL-60
      cells.
AB  - The human acute promyelocytic leukemia (APL) cell line HL-60 differentiates to
      functionally mature granulocytes by incubation with all-trans-retinoic acid (RA).
      Since T3 and RA are important in cell differentiation and development, and since
      their receptors are highly homological, we investigated the T3 effects on RA
      induced HL-60 cell differentiation. Although T3 alone did not induce cell
      differentiation, RA-mediated differentiation was significantly enhanced in the
      presence of 10(-7) M T3. This effect of T3 was considered to be mediated, at
      least in part, by increased intracellular cAMP, since the phosphodiesterase
      inhibitor enhanced, and the protein kinase A antagonist partially blocked, T3
      potentiation. When HL-60 cells were pretreated with RA for 20 h, T3 alone
      stimulated the cell differentiation. The time-course study showed that incubation
      with RA for 12 h was necessary for HL-60 cells to be primed to respond to T3 for
      differentiation. The present finding that T3 potentiates RA-induced HL-60 cell
      differentiation may raise the possibility that T3 supplement increases clinical
      remission in APL patients who are treated with RA.

PMID- 7525381
TI  - Pioglitazone promotes insulin-induced activation of phosphoinositide 3-kinase in
      3T3-L1 adipocytes by inhibiting a negative control mechanism.
AB  - Activation of phosphoinositide 3-kinase (PI 3-kinase) is an early event in
      insulin signal transduction that is blocked completely in adipocytes from insulin
      resistant KKAy mice. Treatment of KKAy mice with pioglitazone, an anti-diabetic
      thiazolidinedione, partially restores insulin-dependent changes in PI 3-kinase.
      The mechanism of this effect of pioglitazone was investigated using murine 3T3-L1
      cells as an experimental model. Insulin and insulin-like growth factor I (IGF-I)
      each elicited rapid (within 2 min) and large (2-5-fold) increases in PI 3-kinase
      activity that could be immunoprecipitated using anti-phosphotyrosine (pY)
      antibodies. Maximal insulin-induced activity of PI 3-kinase in pY
      immunoprecipitates was similar in 3T3-L1 adipocytes and mouse adipocytes, but the
      kinetics of activation differed. Insulin- and IGF-I-induced changes in PI 3
      kinase were each half-maximal at 3-5 nM of hormone and were not additive.
      Increases in both insulin-induced and IGF-I-induced pY-immunoprecipitable PI 3
      kinase activity were observed when 3T3-L1 fibroblasts became confluent and when
      they adopted the adipocyte phenotype. Pioglitazone (10 microM), administered
      either acutely or chronically to either 3T3-L1 adipocytes or 3T3-L1 fibroblasts,
      did not greatly alter the kinetics, magnitude or sensitivity of changes in PI 3
      kinase elicited by either insulin or IGF-I. In contrast, the attenuation by
      isoproterenol of insulin-induced changes in PI 3-kinase was prevented in cells
      pretreated with pioglitazone. This effect of pioglitazone did not involve
      inhibition of isoproterenol-elicited accumulation of cyclic AMP. Pioglitazone
      also prevented attenuation of insulin induced changes in PI 3-kinase by cell
      penetrating analogs of cyclic AMP. Pioglitazone, therefore, has no direct effect
      on insulin-stimulated PI 3-kinase activity, but interferes with a cyclic AMP
      dependent mechanism that normally antagonizes this action of insulin. These data
      support the proposition that the facilitation of insulin action by pioglitazone
      involves, at least in part, an inhibition of a negative control mechanism.

PMID- 7525383
TI  - Transcriptional regulation of plasminogen activator inhibitor-1 expression in
      human synovial fibroblasts by prostaglandin E2: mediation by protein kinase A and
      role of interleukin-1.
AB  - Differential expression of PAI-1 in connective tissues has been associated
      etiologically with some forms of arthritis. Our objective was to delineate the
      mechanisms by which PGE2 and IL-1 beta, inflammatory mediators commonly found at
      sites of inflammation, regulate the expression and synthesis of PAI-1 in human
      synoviocytes. PGE2 (and PGE1) inhibited PAI-1 mRNA expression and secretion in a
      dose-dependent manner with an IC50 (for antigen secretion) of 4.6 x 10(-10) M and
      8.7 x 10(-10) M, respectively. Cyclic AMP agonists forskolin, Sp-cAMP, and IBMX
      mimic the effects of the PGEs. rhIL-1 beta stimulated the secretion of PAI-1 in a
      dose-dependent fashion under basal culture conditions; the effect was reversed by
      actinomycin D and the protein kinase inhibitors H7 and staurosporine but not KT
      5720. PMA, an activator of protein kinase C, transiently increased (maximum 3 h)
      the expression of PAI-1 mRNA by approximately 10-fold, especially the 3.2 kb
      species. However, there was no significant increase in PAI-1 antigen secreted
      into the culture medium after PMA (100-300 nM) treatment. The half-life (t1/2) of
      PAI-1 mRNA, both the 3.2 and 2.2 transcripts was about 9.6 h (mean n = 3) and
      PGE2 has no affect on the stability of both messages. PGE2 reduced the rate of
      PAI-1 gene transcription as judged by run-off assays. The NSAID naproxen (30
      micrograms/ml) induced the expression of PAI-1 mRNA over basal levels and super
      induced the inhibitor's expression above rhIL-1 beta stimulated levels. Our
      results suggest that PGE2 suppresses PAI-1 expression and synthesis by activation
      of the cAMP/PKA system and inhibition of the rate of gene transcription. Data
      concerning the activation of PKC suggest that the expression, synthesis and
      release of the PAI-1 may be differentially regulated in normal human
      synoviocytes.

PMID- 7525384
TI  - Identification of a retinoic acid response element upstream of the rat alpha
      fetoprotein gene.
AB  - Retinoic acid (RA) is known to have potent effects on development and
      differentiation. alpha-Fetoprotein (AFP), an oncodevelopmental protein, is
      transcriptionally activated by RA in several cell lines, but little is known
      about the mechanism of RA regulation of AFP gene expression. In the present
      study, we have identified a RA response element (RARE) in the 5'-flanking region
      of the AFP gene. Using deletion mapping, the RARE was located between -6337 to 
      6266 of the rat AFP 5'-flanking region, which confers RA responsiveness in a
      heterologous promoter. Further sequence analysis of this cis-acting element
      demonstrated a RARE direct repeat sequence of AGGTCA and RARE-like motifs at 
      6327 and -6319, respectively. This far upstream RARE (AFP-RARE1) can specifically
      bind to both RAR and RXR proteins in gel mobility shift assays. In co
      transfections with RAR alpha, beta, gamma and RXR alpha expression vectors, a
      reporter gene construct consisting of the AFP-RARE1 sequence ligated upstream of
      the chloramphenicol acetyltransferase (CAT) gene showed strong RA responsiveness
      to RAR alpha and RXR alpha with 15- and 25-fold increases in CAT activity,
      respectively. Furthermore, responsiveness of AFP-RARE1 to RA was independent of
      orientation. These studies present a novel target for RA action by identifying a
      RARE in the AFP gene.

PMID- 7525385
TI  - Evidence of a stimulatory effect of cyclic AMP on corpus allatum activity in
      Manduca sexta.
AB  - Injection of dibutyryl-cAMP prevents cuticular melanization of black Manduca
      sexta larvae, whose pigmentation is related to a defect in the control of the
      corpus allatum. The cAMP analog has no effect in allatectomized black larvae.
      Significant stimulation of corpus allatum activity was obtained in vitro with
      compounds which elicit or mimic elevated intracellular cAMP levels (dibutyryl-, 8
      bromo-, N6 benzoyl-, and 8-thiomethyl-cAMP, 3-isobutyl-1-methylxanthine), but not
      with dibutyryl-cGMP. Relatively inactive glands, such as those on day 4 of last
      larval stadium or from black mutant larvae, were more sensitive to these
      compounds than glands actively synthesizing JH/JH acid. JH acid synthesis by
      corpora allata taken after pupal commitment in the last larval stadium (days 6
      and 8) was not stimulated by either dibutyryl-cAMP or 3-isobutyl-1
      methylxanthine, but day 8 glands appeared to be inhibited by dibutyryl--cAMP. The
      results indicate that a cAMP second messenger system is involved in the
      transduction of signals which stimulate JH/JH acid synthesis by Manduca corpora
      allata prior to pupal commitment and suggest that it may be involved in the
      inhibition of JH acid synthesis after commitment. They also imply that the
      proposed hemolymph factor to which the black mutant corpora allata are
      differentially sensitive interfaces with the cAMP system.

PMID- 7525386
TI  - Morphogenesis and the cytoskeleton: studies of the Xenopus embryo.
AB  - The morphological transformation from oocyte to embryo is brought about by the
      structural components of the cell, the cytoskeleton. Cytoskeletal elements act to
      generate and maintain cellular asymmetries, cellular movement and morphologies,
      and to integrate signals and forces into morphogenetically coherent behavior.
      Because of its unique experimental accessibility, the Xenopus embryo provides a
      powerful model system in which to study the "body language" of early embryonic
      development.

PMID- 7525388
TI  - Overexpression of XMyoD or XMyf5 in Xenopus embryos induces the formation of
      enlarged myotomes through recruitment of cells of nonsomitic lineage.
AB  - The myogenic regulatory factors (MRFs) MyoD and Myf5 are the earliest described
      muscle-specific genes to be expressed in Xenopus development. To study the in
      vivo effects of overexpressing Xenopus MyoD and Myf5, synthetic RNAs were
      microinjected into single blastomeres of 2- to 32-cell stage Xenopus embryos. In
      vivo overexpression of these MRFs initiates the precocious and ectopic expression
      of actin and myosin. The effects of unilateral injection of either mRNA were
      indistinguishable; embryos injected at the 2-cell stage showed ipsilaterally
      enlarged cranial and anterior trunk myotomes composed of increased numbers of
      primary myotome myocytes. In addition, formation of ectopic muscle in lateral
      plate and neural tissue was observed. The MRF-induced effects persist through
      secondary myogenesis, with the enlarged cranial myotomes failing to undergo the
      normal program of degeneration. Experiments combining MRF RNA and lineage tracer
      injections showed that myotomal enlargement is due in part to the contribution of
      cells of nonsomitic lineage to the myotome, rather than to an increase in muscle
      precursor cell division. Overexpression of XMyoD and XMyf5 also affected the
      morphogenesis of the skin and the nervous system. These results reveal that
      overexpression of XMyoD or XMyf5 in vivo clearly influences the regulation of
      early myogenesis and the morphogenesis of skin and nervous tissue.

PMID- 7525389
TI  - Localized RNAs are enriched in cytoskeletal extracts of Drosophila oocytes.
AB  - Maternal mRNAs localized within the Drosophila oocyte encode positional
      information which specifies the pattern of the early embryo. With the goal of
      identifying molecules involved in RNA localization, we have developed a
      subcellular fractionation procedure which enriches for localized RNAs. Most RNAs
      and cellular proteins are solubilized by this method and are recovered in the
      supernatant fraction. However, five localized RNAs we examined are recovered in
      the detergent-insoluble pellet, despite temporal and spatial differences in their
      patterns of expression. These RNAs appear to be associated with a large,
      detergent-insoluble component of the oocyte. This association is specific for the
      oocyte proper, as localized RNAs in nurse cells and early embryos do not show
      this behavior. The fractionation behavior of these RNAs appears directly related
      to their localization in the oocyte, since fractionation and localization exhibit
      the same cytoskeletal and genetic requirements. The cortical cytoskeleton of the
      oocyte is a likely candidate for the localization substratum.

PMID- 7525390
TI  - Sequential expression of acetylcholine receptor isoforms in mesodermalized
      Xenopus animal caps.
AB  - Exposure of Xenopus animal pole explants to transforming growth factor beta 2
      (TGF-beta 2) induced the sequential expression of muscle nicotinic acetylcholine
      receptor (AChRs) isoforms and their corresponding mRNAs in cells which normally
      give rise to ectoderm. Single channel recordings revealed two functional classes
      of receptors with properties similar to those expressed during normal development
      of skeletal muscle in vivo. The predominant class of receptors in all patches
      corresponded to those of embryonic myotomal muscle. Additional receptors
      resembling those of mature myotomal muscle were observed in older explants.
      Levels of transcripts encoding the embryonic and adult AChR subunit isoforms
      varied accordingly. TGF-beta 2 appears to initiate a developmental program of
      AChR gene expression which is similar to that found in normally developing
      muscle.

PMID- 7525387
TI  - Sequence of a rabbit sperm zona pellucida binding protein and localization during
      the acrosome reaction.
AB  - The interaction of the mammalian spermatozoon with the oocyte's extracellular
      matrix or zona pellucida is a critical first step leading to successful
      fertilization. In this cell-extracellular matrix interaction it is the
      carbohydrate of the zona pellucida which serves as the sperm receptor and the
      surface of the spermatozoon which provides the lectin-like adhesion molecules. To
      better understand sperm-zona pellucida binding we have analyzed one specific zona
      binding protein (ZBP). This study has determined the mRNA sequence encoding a
      mammalian testis and sperm specific protein of 16,891 Da, which we have
      designated Sp17. Analysis of Sp17 revealed that the mRNA is present in rabbit,
      mouse, and human testes but not in any somatic tissue tested. In the rabbit, Sp17
      is the 17-kDa member of the rabbit sperm autoantigen family of sperm specific
      autoantigens and is encoded by two mRNAs of 0.9 and 1.1 kb. Each mRNA has a
      unique 5' untranslated region but both have identical coding regions. The deduced
      amino acid sequence of the Sp17 ZBP showed several interesting features,
      including a similarity to the N-terminal of human testis cAMP-dependent protein
      kinase. Localization of Sp17 on live spermatozoa using antibodies to recombinant
      Sp17 or to the Sp17 peptide, G22C, revealed that the peptide backbone of Sp17 is
      inaccessible until the acrosome reaction begins. However, on paraformaldehyde
      fixed, acrosome intact spermatozoa, the peptide backbone is accessible to the
      antibodies which localize Sp17 to the apical surface. In the rabbit as well as
      other similar species in which the corona radiata (granulosa) cells adhere
      tightly to the zona pellucida and synthesize zona glycoproteins, the fertilizing
      spermatozoon may have already begun the acrosome reaction within the cumulus
      oophorus. Thus, the rabbit sperm surface would be modified to expose the Sp17
      polypeptide during the final phase of cumulus passage and consequently Sp17 would
      be available for initial zona binding. The present study has also demonstrated
      that recombinant Sp17 can bind zona pellucida, dextran, and dextran sulfate.

PMID- 7525392
TI  - Introduction of foreign sequences into the genome of influenza A virus.
AB  - The ability to apply reverse genetics technologies to influenza virus now allows
      us to construct novel viruses containing heterologous sequences. We have
      engineered two neuraminidase (NA) genes of influenza A/WSN/33 virus containing
      additional sequences which were inserted downstream of the open reading frame of
      the NA. These NA genes, NA/EMC and NA/EMC-NS1, possess a 546 and a 917 nucleotide
      (nt) insertion respectively. Transfectant viruses were rescued following
      ribonucleoprotein (RNP) transfection of the engineered NA genes into influenza
      helper-virus-infected cells. The transfectant viruses maintained their
      artificially introduced sequences stably during three passages. The rescued virus
      containing the NA/EMC-NS1 gene produced one log fewer infectious virus particles
      in MDBK cells than did wild type A/WSN/33 virus. The growth characteristics in
      tissue culture of the virus containing the NA/EMC gene was indistinguishable from
      that of wild-type influenza virus. Based on these results we conclude that
      influenza A viruses can tolerate heterologous insertions of at least a kilobase
      in the NA gene.

PMID- 7525391
TI  - Molecular and cellular parameters controlling the immunogenicity of foreign B- or
      T-cell epitopes expressed by recombinant vectors.
AB  - Extensive work is being performed to develop live recombinant bacterial vaccines.
      The use of non-pathogenic bacteria or attenuated strains derived from pathogens
      may allow protection against the pathogen and at the same time induce immunity
      against one or several foreign antigens expressed by the recombinant micro
      organism. Several bacteria such as attenuated Salmonella or BCG have been used
      successfully in several experimental models to induce protective immune responses
      against several pathogens. However, the presentation to the immune system of a
      foreign antigen in a context different from the natural one may greatly modify
      the characteristics of elicited immune responses. It is therefore of the utmost
      importance to establish rules concerning the influence of the vector on the
      immunogenicity of recombinant antigens. Using a bacterial system that allows the
      expression of genetically engineered hybrid proteins, we have analysed: 1) the
      role of the molecular environment on the immunogenicity of foreign B- or T-cell
      epitopes; 2) the influence of the cellular location of a foreign B-cell epitope
      on the induction of specific immune responses; 3) the role of the bacterial
      vector (E. coli or Salmonella typhimurium) on the isotypic characteristic of
      antibody responses induced against the recombinant antigen. These studies
      revealed the complexity of the mechanisms which control the immunogenicity of
      foreign B- or T-cell epitopes expressed by recombinant vectors.

PMID- 7525394
TI  - Methylphenidate and ADHD: influence of age, IQ and neurodevelopmental status.
AB  - Sixty-nine children with attention deficit hyperactivity disorder (ADHD)
      underwent blind methylphenidate trials. 36 had ADHD alone (with or without a
      learning disability) and 33 had additional neurodevelopmental disorders. Of the
      children with ADHD alone, 88 per cent improved significantly on methylphenidate.
      This did not differ significantly from the 69 per cent response rate for children
      with ADHD and other neurodevelopmental disorders. The results confirm and add to
      the research literature indicating that ADHD children who are of preschool age
      and/or who have co-existing neurological disorders may benefit from
      methylphenidate.

PMID- 7525395
TI  - American Academy for Cerebral Palsy and Developmental Medicine. Annual meeting,
      September 29-October 1, 1994, New Orleans, Louisiana. Abstracts.

PMID- 7525396
TI  - Bibliography of developmental medicine and child neurology: selected books and
      articles received in 1993.

PMID- 7525393
TI  - Immunization with the larger isoform of mouse glutamic acid decarboxylase (GAD67)
      prevents autoimmune diabetes in NOD mice.
AB  - The 65-kDa isoform of glutamic acid decarboxylase (GAD65) has been implicated in
      autoimmune diabetes in NOD mice, but the role of the 67-kDa GAD isoform (GAD67)
      is less clear. We found that immunization of 4-week-old NOD mice with purified
      recombinant mouse GAD67 prevented or significantly delayed the onset of diabetes.
      To further explore this phenomenon, we characterized anti-GAD67 immune responses
      in naive and GAD-immunized NOD mice. Anti-GAD67 antibodies titers were relatively
      low in naive mice at all ages, but a single immunization with GAD67 at 4 weeks
      induced high titers of anti-GAD antibodies by 6 weeks of age. In both 4-week-old
      and diabetic NOD mice, there were significant endogenous T-cell proliferative
      responses against purified recombinant mouse GAD67. These T-cell proliferative
      responses were blocked by anti-I-ANOD and anti-CD4 antibodies. To characterize
      the anti-GAD T-cell responses in the NOD mice, we established T-cell lines and T
      cell clones which recognized GAD67, and we used recombinant subfragments of GAD
      to localize the predominant T-cell epitopes in GAD67. T-cells from naive NOD mice
      proliferated in response to all GAD subfragments, whereas T-cells from diabetic
      mice responded primarily to the COOH-terminal 83 amino acids of GAD67. These
      results suggest that GAD67 is an autoantigen in IDDM and immunization of
      prediabetic NOD mice with GAD67 can prevent the onset of diabetes.

PMID- 7525398
TI  - The level of the zymogen granule protein GP2 is elevated in a rat model for acute
      pancreatitis.
AB  - BACKGROUND/AIMS: GP2 is the major membrane protein in pancreatic zymogen
      granules. It is linked to the membrane via a glycosyl-phosphatidylinositol
      linkage. After cleavage, a significant fraction of GP2 becomes soluble. The
      present study assessed whether GP2 is a useful serum marker for acute
      pancreatitis. METHODS: Using an anti-GP2 monoclonal antibody, an enzyme-linked
      immunosorbent assay was developed to measure the serum levels of GP2 in rats with
      cerulein-induced acute pancreatitis. RESULTS: The anti-GP2 antibody was specific
      because it did not cross-react with uromodulin, a structurally similar protein to
      GP2, or to protein extracts from nonpancreatic tissues. Eight hours after the
      induction of pancreatitis, the serum levels of amylase, lipase, and GP2 peaked.
      Peak GP2 levels were 4.2 times higher than those of controls. At 24 hours, GP2
      was still 70% of the peak level, whereas amylase and lipase were 5.5% and 0.5%,
      respectively, of their peak levels. CONCLUSIONS: GP2 may serve as a potentially
      valuable marker for clinical acute pancreatitis.

PMID- 7525397
TI  - Neuroimmune communication in the submucous plexus of guinea pig colon after
      infection with Trichinella spiralis.
AB  - BACKGROUND/AIMS: Enteric neuroimmune communication in gastrointestinal
      hypersensitivity responses includes antigen detection by mast cells and release
      of chemical messages to the enteric nervous system. The aim of this study was to
      analyze the electrical and synaptic behavior of neurons in the colonic submucous
      plexus during exposure to Trichinella spiralis antigen in animals infected
      earlier with the parasite. METHODS: Microelectrodes were used to record in
      submucous neurons of guinea pig distal colon during application of Trichinella
      antigen. RESULTS: Neurons in sensitized animals were more excitable than in
      controls. Hyperexcitability was seen as a greater probability of spontaneous
      action potential discharge and repetitive firing to depolarizing current or
      exposure to acetylcholine. Application of histaminergic antagonists reversed the
      augmented excitability, suggesting endogenously released histamine as a
      responsible factor. Antigenic exposure increased neuronal excitability and
      suppressed nicotinic transmission at fast cholinergic synapses only in sensitized
      animals. Effects on excitability, but not presynaptic inhibitory effects, were
      blocked by cimetidine. CONCLUSIONS: Signaling between mucosal mast cells and the
      enteric nervous system is involved in colonic anaphylactic responses to
      sensitizing antigens. Histamine is a paracrine signal in the communication
      pathway.

PMID- 7525400
TI  - Effects of vasoactive intestinal peptide and its homologues on the substance P
      mediated secretion of fluid and protein from the rat submandibular gland.
AB  - 1. Vasoactive intestinal peptide (VIP) and secretin elicited slight secretion of
      saliva but peptide histidine isoleucine (PHI) and gastric inhibitory peptide
      (GIP) failed to elicit secretion of saliva from rat submandibular glands. 2.
      Substance P (SP)-mediated secretion of fluid and protein were enhanced by VIP and
      secretin but not by PHI or GIP. 3. These results suggest that the effects of VIP,
      PHI, secretin and GIP on the secretion of fluid from rat submandibular glands and
      the synergistic effects of VIP and its homologues on the SP-mediated secretion of
      fluid and protein do not correspond to the extent of the structural homology of
      each analogue to VIP.

PMID- 7525399
TI  - Palliation for advanced esophageal cancer: hope at last?

PMID- 7525403
TI  - Variable expression of O-antigen and the role of lipopolysaccharide as an adhesin
      in Aeromonas sobria.
AB  - On initial isolation of Aeromonas sobria 3767 from a diarrhoeal stool specimen,
      two colony types were obtained: opaque (3767O) and translucent (3767T). Strain
      3767O consistently produced lipopolysaccharide (LPS) core and O-antigen side
      chain, detectable by SDS-PAGE and by Western blotting with an O-antigen-specific
      monoclonal antibody. Strain 3767T produced LPS core but the amount of O-antigen
      was dependent on factors including growth medium and bacterial growth phase.
      Strain 3767T exhibited significantly lower levels of adhesion to HEp-2 cells than
      3767O and this correlated with the level of LPS expression, with the greatest
      reduction (61%) at stationary phase when no LPS was detectable. The results
      implicate LPS as an adhesin for A. sobria 3767.

PMID- 7525402
TI  - Characterization of cDNA-encoding N-terminal region of the quail lutropin
      receptor.
AB  - For understanding the evolutionary relationships between gonadotropins [GTHs:
      lutropin (LH) and follitropin (FSH)] and their receptors, we attempted to
      characterize the extracellular domain of the receptors, which is thought to be a
      key region of hormone binding, in nonmammalian species, and to compare the
      information to that of the known mammalian data. For this purpose, we designed
      two sets of sense and antisense oligonucleotides as polymerase chain reaction
      (PCR) primers, referring to the known mammalian GTH receptors, such as LH
      receptors of human, pig, and rat, and FSH receptors of human and rat. All
      possible combinations of the primers showed the successful amplification of cDNA
      of LH receptor without contamination of FSH receptor cDNA from rat testicular RNA
      samples. With these primers, reverse transcription (RT)-PCR was applied to the
      gonads of nonmammalian species (quail, snake, tortoise, newt, and bullfrog). Only
      the quail, however, showed the specific amplification when only one set of
      primers was used. Thus, the PCR product of the quail was used as a probe for
      Northern blot and in situ hybridization. By Northern blot analysis, a single size
      of mRNA (3 kb) was identified from quail testicular poly A+ RNA. The distribution
      of mRNA visualized by in situ hybridization was limited only on Leydig cells of
      quail testis. These results suggest that a part of the quail LH receptor cDNA was
      amplified by RT-PCR. The nucleotide and predicted peptide sequences of this
      amplified cDNA were compared with those of mammalian receptors. The size of
      characterized cDNA sequence was 519 bp, which is completely identical with those
      of mammalian LH receptors. The homology of both cDNA and predicted peptide was
      about 70% of those of mammalian LH receptors (intramammalian, about 80%). In
      spite of the relatively low homology, the positions of cystein residues and
      potential N-linked glycosylation sites in the peptide were completely conserved
      in all species compared (human, pig, rat, and quail). The conserved portions
      indicate their importance for the molecular conformation and specific ligand
      binding activity of LH receptors.

PMID- 7525401
TI  - The two nonallelic Xenopus insulin genes are expressed coordinately in the adult
      pancreas.
AB  - We have previously shown that the two nonallelic insulin genes in Xenopus laevis
      are expressed differentially during neurulation in prepancreatic embryos
      (Shuldiner et al., 1991, Proc. Natl. Acad. Sci. USA 88, 7679-7683). We now
      examine pancreatic expression with alterations in ambient temperature, glucose
      administration, fasting and feeding, somatostatin analog treatment, as well as
      during postmetamorphic growth. Insulin I and II mRNAs were quantitated by slot
      blot hybridization with specific probes and were expressed as the number of
      copies (x 10(8)) per 5 micrograms total RNA +/- SEM. Frogs maintained at 12
      degrees showed no significant changes when compared to frogs maintained at 20
      degrees. There was a coordinate decrease in insulin I and II mRNA levels in frogs
      maintained at 29 degrees (Ins I 20, 3.41 +/- 0.34 vs Ins I 29, 2.39 +/- 0.17; Ins
      II 20, 2.59 +/- 0.36 vs Ins II 29, 1.67 +/- 0.09; P < 0.05). When compared to
      fasting animals, both insulin I and II mRNA levels decreased slightly in frogs
      given repeated intraperitoneal injections of glucose and in those fed ad libitum;
      there were no changes after a single dose of glucose or in frogs given
      somatostatin. When compared to young frogs (6 to 24 months), older frogs (36
      months) had higher insulin I and II mRNA levels (e.g., Ins I 6mo, 2.14 +/- 0.15
      vs Ins I 36mo, 3.68 +/- 0.43; Ins II 6mo, 1.21 +/- 0.06 vs Ins II 36mo, 3.26 +/-
      0.38; P < 0.05). Further, there was a modest reduction in the percentage of
      insulin I mRNA with aging (e.g., 6 months 63.6 +/- 3.1% vs 36 months 53.9 +/-
      2.7%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525404
TI  - [Portion of certain cystic fibrosis gene mutations and linkage dysequilibrium
      between the CFTR-gene locus and two DNA marker loci in Russian populations].
AB  - A sample of 165 patients who were inhabitants of Russia was screened for seven
      CFTR gene mutations, and analysis of polymorphism frequency at two marker loci
      (KM19 and VNTR in intron 6 of the CFTR gene) was performed in normal and mutant
      chromosomes. The frequencies of mutations in 330 mutant chromosomes were
      distributed as follows: delta F508, 57.5%; G542X, 1.07%; and R33AW, 0.45%.
      Mutations G551D, R553X, R347P, and 1154insTC were not found. Alleles and
      haplotypes of KM19 and VNTR loci in intron 6 of the CFTR gene were characterized
      by a marked linkage disequilibrium with the CFTR gene. Haplotype 2-6 showed an
      absolute linkage disequilibrium with the delta F508 mutation.

PMID- 7525405
TI  - The cellular concentration of the sigma S subunit of RNA polymerase in
      Escherichia coli is controlled at the levels of transcription, translation, and
      protein stability.
AB  - The second vegetative sigma factor sigma S (encoded by the rpoS gene) is the
      master regulator in a complex regulatory network that governs the expression of
      many stationary phase-induced and osmotically regulated genes in Escherichia
      coli. Using a combination of gene-fusion technology and quantitative immunoblot,
      pulse-labeling, and immunoprecipitation analyses, we demonstrate here that
      rpoS/sigma S expression is not only transcriptionally controlled, but is also
      extensively regulated at the levels of translation and protein stability. rpoS
      transcription is inversely correlated with growth rate and is negatively
      controlled by cAMP-CRP. In complex medium rpoS transcription is stimulated during
      entry into stationary phase, whereas in minimal media, it is not significantly
      induced. rpoS translation is stimulated during transition into stationary phase
      as well as by an increase in medium osmolarity. A model involving mRNA secondary
      structure is suggested for this novel type of post-transcriptional growth phase
      dependent and osmotic regulation. Furthermore, sigma S is a highly unstable
      protein in exponentially growing cells (with a half-life of 1.4 min), that is
      stabilized at the onset of starvation. When cells are grown in minimal glucose
      medium, translational induction and sigma S stabilization occur in a temporal
      order with the former being stimulated already in late exponential phase and the
      latter taking place at the onset of starvation. Although sigma S does not control
      its own transcription, it is apparently indirectly involved in a negative
      feedback control that operates on the post-transcriptional level. Our analysis
      also indicates that at least five different signals [cAMP, a growth rate-related
      signal (ppGpp?), a cell density signal, an osmotic signal, and a starvation
      signal] are involved in the control of all these processes that regulate
      rpoS/sigma S expression.

PMID- 7525406
TI  - Allele-specific gene expression in mammals: the curious case of the imprinted
      RNAs.

PMID- 7525407
TI  - A functional "knockout" of human keratin 14.
AB  - The importance of keratins and other intermediate filaments in the maintenance of
      tissue structure is emphasized by the discovery that many hereditary skin
      blistering diseases are caused by mutations in keratin genes. Here, we describe a
      situation in which keratin 14 (K14) is missing altogether in the epidermis: A
      homozygous 2-nucleotide deletion in exon I of the K14 gene causes premature
      termination of the mRNA transcripts upstream from the start of the rod domain and
      results in a K14 null phenotype. In this individual no keratin intermediate
      filaments are visible in basal epidermal cells, although filaments are present in
      the upper layers of the epidermis. No compensating keratin expression is detected
      in vivo, and K14 mRNA is down-regulated. The individual, diagnosed as Kobner
      (generalized) EBS, suffers from severe widespread keratinocyte fragility and
      blistering at many body sites, but although the phenotype is severe, it is not
      lethal. This K14-/- phenotype confirms that only one K14 gene is expressed in
      human epidermis and provides an important model system for examining the
      interdependence of different keratin filament systems and their associated
      structures in the skin.

PMID- 7525408
TI  - A human keratin 14 "knockout": the absence of K14 leads to severe epidermolysis
      bullosa simplex and a function for an intermediate filament protein.
AB  - Since their discovery, the function of intermediate filaments (IFs) has remained
      obscure. In skin, epidermal cells have extensive cytoskeletal architectures of
      IFs, composed of type I and type II keratin heterodimers. Clues to possible
      functions of these proteins have come from recent studies showing that several
      autosomal-dominant, blistering skin disorders are caused by defects in genes that
      encode epidermal keratins. These diseases all exhibit cell degeneration and
      keratin network perturbations in cells that express the particular mutant keratin
      gene. However, it is not clear from these studies whether cytolysis arises from
      the presence of large insoluble keratin aggregates that compromise cellular
      physiology or from the absence of an extensive keratin filament network, which
      jeopardizes mechanical integrity. We report here the analysis of an extremely
      rare case of severe recessive epidermolysis bullosa simplex (EBS), where the
      patient lacks a discernible keratin filament network in basal epidermal cells.
      Genetic analyses revealed a homozygous point mutation that yielded a premature
      termination codon in the major basal type I keratin gene and caused complete
      ablation of K14. The consanguineous parents were normal, each harboring one copy
      of the null K14 mutation. Analysis of cultured keratinocytes enabled us to
      document that the loss of K14 is not compensated for by the up-regulation of any
      other type I keratin. When taken together with the in vivo studies showing the
      presence of cell fragility generated from the lack of an extensive basal keratin
      network, these findings provide the first clear demonstration of loss of function
      associated with the absence of an IF protein in vivo.

PMID- 7525409
TI  - Adaptive significance of amylase polymorphism in Drosophila. VIII. Effect of
      carbohydrate dietary components on alpha-amylase activity and Amy-electromorph
      frequency in Drosophila busckii.
AB  - Laboratory populations of D. busckii flies were kept for one generation on media
      containing different carbohydrate sources (maltose and rice, potato or maize
      starch). The flies maintained on standard potato medium served as a control.
      Progeny were analyzed for alpha-amylase activity and Amy-electromorph
      frequencies. Spectrophotometrically assayed amylase activity was highest in the
      flies cultured on potato starch medium and lowest in specimens kept on maltose.
      Carbohydrate source in some substrates affected both frequencies of Amy-alleles
      and Amy-genotypes. Phenotypic differences at a biochemical level, i.e. in alpha
      amylase activity, might be connected to Amy-structural gene polymorphism in the
      examined Drosophila species.

PMID- 7525411
TI  - Effects of deoxyribonucleotide substitutions in the substrate strand on
      hammerhead ribozyme-catalyzed reactions.
AB  - In order to examine the effects of deoxyribonucleotide substitutions in the
      substrate strand, several chimeric DNA/RNA substrates for a hammerhead ribozyme
      were chemically synthesized. Measurements of kinetic parameters revealed that a
      chimeric DNA/RNA substrate, that contained GUC at the cleavage site as
      ribonucleotides, was cleaved by an all-RNA ribozyme with a threefold higher kcat
      than that of the wild-type (wt) reaction. Moreover, this chimeric substrate was
      also cleaved by a DNA-armed ribozyme that has a higher kcat than the all-RNA
      ribozyme [Shimayama et al., Nucleic Acids Res. 21 (1993) 2605-2611], with a
      fourfold higher kcat than that of the wt reaction. Km was increased stepwise by
      60-fold per substitutions of the strand of stems I and III by
      deoxyribonucleotides. These observations demonstrate that although substitutions
      by deoxyribonucleotides in stems I and III decrease the affinity of substrate and
      ribozyme, rates of chemical cleavage are actually increased, instead of being
      decreased, with substitutions by deoxyribonucleotides either on the substrate
      side or on the ribozyme side or even on both in our system.

PMID- 7525410
TI  - Single-strand-targeted triplex formation: stability, specificity and RNase H
      activation properties.
AB  - Single-stranded (ss) oligodeoxyribonucleotides (oligos) containing both Watson
      Crick and Hoogsteen hydrogen bonding domains joined by either a 5-nucleotide loop
      or a flexible hexaethylene-glycol linker, called foldback triplex-forming oligos
      (FTFOs), are designed and studied for their binding affinity and specificity to
      their ss DNA/RNA targets. Thermal denaturation studies revealed an increased
      affinity of FTFOs, due to addition of a Hoogsteen hydrogen bonding domain at the
      binding site, as the Watson-Crick domain forms a double helix with the target,
      when compared to conventional antisense and antigene oligos. DNase I hydrolysis
      and electrophoretic mobility shift analysis confirmed the formation of foldback
      triplexes relative to conventional double- and triple-stranded structures. The
      FTFOs showed increased sequence specificity mainly arising from their ability to
      recognize the target sequence twice, first by Watson-Crick base pairing and a
      second time by Hoogsteen base pairing. An FTFO with DNA components in both duplex
      and triplex-forming domains showed preference for a DNA homopurine target
      strand.

PMID- 7525412
TI  - The purine 2-amino group as a critical recognition element for binding of small
      molecules to DNA.
AB  - The expedient of preparing homologous DNA samples substituted with I for G, DAP
      for A, or both, has been used to investigate the role of the purine 2-amino group
      in determining the preferred binding sites for antibiotics on DNA. The
      selectivity of echinomycin for CpG steps, of actinomycin for GpC steps, and of
      netropsin for A + T-rich tracts, is seen to be radically altered in the
      substituted DNA molecules.

PMID- 7525413
TI  - Insertion of a HIV-1-neutralizing epitope in a surface-exposed internal region of
      the cholera toxin B-subunit.
AB  - The non-toxic B-subunit of cholera toxin (CTB) is a powerful immunogen and has
      been investigated as a carrier for foreign peptide epitopes, with peptides
      genetically fused to either the N- or C terminus of CTB. In the present study, we
      have constructed a plasmid encoding a novel intrachain CTB fusion protein with a
      peptide epitope inserted into an internal region of CTB: eight amino acids (aa)
      in CTB (56-63) were substituted with a 10-aa peptide from the third variable (V3)
      loop of the HIV-1 envelope protein gp120. The resulting chimeric protein retained
      important functional characteristics of the native CTB including pentamerization
      and GM1 ganglioside receptor binding. The internal hybrid protein was also shown
      to be resistant to proteolytic degradation during production in Vibrio cholerae,
      whereas a terminal hybrid protein, where the same gp120-epitope was fused to the
      N terminus of CTB, was rapidly cleaved during culture. The inserted epitope,
      which is known to give rise to HIV-1 neutralizing Ab, could be detected with a V3
      loop-specific monoclonal Ab when the chimeric protein was analyzed in ELISA and
      immunoblot, indicating that the epitope inserted at this site is presented on the
      surface of the protein. Consistent with these observations, immunization of mice
      with the CTB::HIV hybrid protein elicited a high titered serum Ab response to the
      CTB moiety and also, in some but not all animals, a detectable response to the
      inserted gp120 epitope.

PMID- 7525415
TI  - PSA guidelines disputed by physician with personal experience.

PMID- 7525414
TI  - Tas, a retrotransposon from the parasitic nematode Ascaris lumbricoides.
AB  - The cloned retrotransposon Tas OE3 from the genome of the parasitic nematode
      Ascaris lumbricoides was completely sequenced. The element is flanked by long
      terminal repeats (LTR) and contains three distinct regions encoding putative
      proteins typical for retroid elements. The first region, ORF1, encodes a putative
      Gag protein including a 'Leu zipper', a nucleic acid binding motif, as well as an
      aspartic protease domain. The second region contains an incomplete ORF (ORF2)
      with sequence similarities to known retroviral reverse transcriptases (RT),
      ribonucleases H and integrases. A third ORF, which is located adjacent to the 3'
      LTR, might encode an env-like protein. Based on amino-acid sequence analysis of
      the RT domain, Tas falls into a new subgroup of LTR-containing retrotransposons.

PMID- 7525416
TI  - BPH artwork: real vs. conceptual.

PMID- 7525418
TI  - Effect on lymph node status of triple levelling and immunohistochemistry with CAM
      5.2 on node negative colorectal carcinomas.
AB  - Several papers have recently assessed whether immunohistochemistry increases the
      accuracy of staging in node negative colorectal carcinomas, by showing
      micrometastases. The results have been contradictory. In this paper 542 nodes
      which were negative for tumour on routine sectioning, were stained with CAM 5.2.
      In addition, the tissue was levelled three times, this technique being more
      economical, to see if either or both techniques increased the pick up of
      micrometastases. Six nodes showed positive staining of occasional cells in the
      subcapsular and paracortical sinuses, but these were cytologically benign on
      review and were not thought to represent metastatic tumour. Triple levelling did
      not show any additional micrometastases.

PMID- 7525419
TI  - Chronic ethanol consumption increases the fragility of rat pancreatic zymogen
      granules.
AB  - Intracellular activation of pancreatic digestive enzymes by lysosomal hydrolases
      is thought to be an early event in the pathogenesis of pancreatic injury. As
      ethanol excess is an important association of pancreatitis, experimental work has
      been directed towards exploring possible mechanisms whereby ethanol may
      facilitate contact between inactive digestive enzyme precursors and lysosomal
      enzymes. The aim of this study was to find out if chronic ethanol administration
      increases the fragility of rat pancreatic zymogen granules. Sixteen male Sprague
      Dawley rats were pair fed ethanol and control liquid diets for four weeks.
      Zymogen granule fragility was then assessed in pancreatic homogenate by
      determination of (a) latency and (b) per cent supernatant enzyme after
      sedimentation of zymogen granules. Amylase was used as a zymogen granule marker
      enzyme. Latency was significantly reduced in pancreatic homogenates of ethanol
      fed animals suggesting increased zymogen granule fragility. In support of this
      finding, there was a trend towards increased supernatant enzyme after ethanol
      feeding. In conclusion, administration of ethanol increases the fragility of
      pancreatic zymogen granules in the absence of morphological evidence of
      pancreatic injury. It is proposed that zymogen granule fragility may play an
      early part in the pathogenesis of alcoholic pancreatitis by permitting contact
      between digestive and lysosomal enzymes.

PMID- 7525417
TI  - Enhanced gastric nitric oxide synthase activity in duodenal ulcer patients.
AB  - Nitric oxide, the product of nitric oxide synthase in inflammatory cells, may
      have a role in tissue injury through its oxidative metabolism. Nitric oxide may
      have a role in the pathogenesis of duodenal ulcer and may be one of the
      mechanisms responsible for the association between gastric infection with
      Helicobacter pylori and peptic disease. In this study, calcium independent nitric
      oxide synthase activity was detected in human gastric mucosa suggesting
      expression of the inducible isoform. In 17 duodenal ulcer patients gastric antral
      and fundic nitric oxide synthase activity was found to be two and 1.5-fold
      respectively higher than its activity in the antrum and fundus of 14 normal
      subjects (p < 0.05). H pylori was detected in the antrum of 15 of 17 duodenal
      ulcer patients and only in 7 of 14 of the control subjects. Antral nitric oxide
      synthase activity in H pylori positive duodenal ulcer patients was twofold higher
      than in H pylori positive normal subjects (p < 0.05). In duodenal ulcer patients
      antral and fundic nitric oxide synthase activity resumed normal values after
      induction of ulcer healing with ranitidine. Eradication of H pylori did not
      further affect gastric nitric oxide synthase activity. These findings suggest
      that in duodenal ulcer patients stimulated gastric mucosal nitric oxide synthase
      activity, though independent of the H pylori state, may contribute to the
      pathogenesis of the disease.

PMID- 7525421
TI  - Role of gastric blood flow, neutrophil infiltration, and mucosal cell
      proliferation in gastric adaptation to aspirin in the rat.
AB  - Gastric mucosa exhibits the ability to adapt to ulcerogenic action of aspirin but
      the mechanism of this phenomenon is unknown. In this study, acute gastric lesions
      were produced by single or repeated doses of acidified aspirin in rats with
      intact or resected salivary glands and with intact or suppressed synthase of
      nitric oxide. A single oral dose of aspirin produced a dose dependent increase in
      gastric lesions accompanied by considerable blood neutrophilia and mucosal
      neutrophil infiltration, significant reduction in gastric blood flow, and almost
      complete suppression of biosynthesis of prostaglandins. After rechallenge with
      aspirin, the mucosal damage became smaller and progressively declined with
      repeated aspirin insults. Gastric adaptation to aspirin was accompanied by a
      significant rise in gastric blood flow, reduction in both blood neutrophilia and
      mucosal neutrophil infiltration, and a remarkable increase in mucosal cell
      regeneration and mucosal content of epidermal growth factor. Salivectomy, which
      reduced the mucosal content of epidermal growth factor, aggravated the initial
      mucosal damage induced by the first exposure to acidified aspirin but did not
      prevent the adaptation of this mucosa to repeated aspirin insults. Pretreatment
      with NG-nitro-L-arginine (L-NNA), a specific inhibitor of nitric oxide synthase,
      eliminated the hyperaemic response to repeated aspirin but did not abolish the
      development of adaptation to aspirin showing that the maintenance of the gastric
      blood flow plays little part in this adaptation. In conclusion, the stomach
      adapts readily to repeated aspirin insults and this is accompanied by a
      considerable reduction in blood neutrophilia and the severity of neutrophil
      infiltration and by an extensive proliferation of mucosal cells possibly
      involving epidermal growth factor.

PMID- 7525420
TI  - Hepatocyte and immune system: acute phase reaction as a contribution to early
      defence mechanisms.

PMID- 7525422
TI  - Trypsinogen activation peptides (TAP) concentrations in the peritoneal fluid of
      patients with acute pancreatitis and their relation to the presence of
      histologically confirmed pancreatic necrosis.
AB  - This study measured the volume and colour, as well as concentrations of
      trypsinogen activation peptides (TAP) in the peritoneal fluid of 22 patients with
      acute pancreatitis and related these findings to the presence of pancreatic
      necrosis. Nine patients had a severe attack with histologically confirmed
      pancreatic necrosis, seven a severe attack without confirmed necrosis, and six a
      mild attack, also without confirmed necrosis. A free fluid volume > 20 ml or free
      fluid colour > grade 5 on the Leeds chart, or both detected histologically
      confirmed pancreatic necrosis with a sensitivity of 100% and specificity of 31%.
      A total peritoneal fluid TAP concentration of > or = nmol detected histologically
      confirmed pancreatic necrosis with a sensitivity of 89% and specificity of 85%,
      figures comparable with contrast enhanced computed tomography. These findings
      suggest that the measurement of peritoneal fluid TAP concentrations can detect
      effectively histologically confirmed pancreatic necrosis and that such
      measurements may prove useful in the selection of patients for surgery.

PMID- 7525423
TI  - Recombinant virus-like particles retain conformational epitopes of native human
      papillomaviruses and may be useful for vaccine development.

PMID- 7525425
TI  - Natural killer cell activity in stage I endometrial carcinoma: correlation with
      nuclear grading, myometrial invasion, and immunoreactivity of proliferating cell
      nuclear antigen.
AB  - The purpose of this study was to examine the relationship between natural killer
      cell activity and biological behavior of tumor, expressed by architectural (FIGO)
      and nuclear grading, depth of myometrial invasion, and proliferating cell nuclear
      antigen (PCNA) index in patients with endometrial carcinoma. Forty patients with
      FIGO stage I endometrial carcinoma, treated with radical surgery, were included
      in this retrospective study. At the time of diagnosis, natural killer cell
      activity of peripheral blood was evaluated against K562 target tumor cells and
      correlated with architectural and nuclear grading, depth of myometrial invasion,
      and PCNA index of the tumor. Natural killer activity diminished with increasing
      nuclear grade of the tumor (P = 0.004); similarly, natural cytotoxicity decreased
      with myometrial invasion: for stages IC and IB endometrial carcinoma, the mean
      values of natural cytotoxicity were significantly lower than stage IA disease (P
      = 0.0001). Natural killer activity was significantly correlated with PCNA
      immunostaining of the tumor (r = -0.8). It is concluded that the natural immune
      reactivity seems to be related to the pathologic features of early stage
      endometrial carcinoma, showing a significant reduction in presence of nuclear
      pleomorphism and/or myometrial invasion, and also an inverse relationship with
      PCNA index.

PMID- 7525424
TI  - The evaluation of PCNA/cyclin expression in cervical intraepithelial lesions.
AB  - This study aims at evaluating the expression of PCNA/cyclin in the cells of
      cervical intraepithelial lesions. The material constituted 121 colposcopic
      biopsies from patients with cytological and/or colposcopical evidence of
      condyloma (HPV) or CIN. The cases were classified as follows: 20 as koilocytosis,
      31 as CIN I and HPV, 30 as CIN II and HPV, 1 as CIN III and HPV, and 7 as CIN
      III. Immunohistochemical detection of PCNA/cyclin was performed on paraffin
      sections by the avidin-extravidin method using the monoclonal antibody PC10
      (DAKO). According to our results a statistically significant difference was
      observed between all groups of our material (P < 0.01). The expression of PC10
      may thus offer useful information on the proliferation capacity of a CIN lesion
      with regard to the histological pattern. Moreover, this method is simple and
      reproducible, requiring no specialized equipment or medical staff.

PMID- 7525426
TI  - Role of conformational epitopes expressed by human papillomavirus major capsid
      proteins in the serologic detection of infection and prophylactic vaccination.
AB  - Human papillomaviruses (HPVs) cause a variety of cutaneous warts, mucosal
      condylomata, and dysplasias and are etiologic in cervical cancer. Papillomavirus
      (PV) conformational epitopes on the surface of virions are type-specific and are
      the target of neutralizing antibodies. In this study, we describe two methods of
      in vitro expression of HPV major capsid (L1) proteins which mimicked
      conformational epitopes and demonstrate their type specificity and ability to
      react with neutralizing and/or conformation-dependent antibodies. The L1 open
      reading frames (ORFs) for HPV-1, 6, 11, and 16 were molecularly cloned into a SV
      40 expression vector and the encoded gene products were expressed in mammalian
      (cos) cells. Similarly, the L1 ORFs for HPV-6, 11, 16, and 18 were molecularly
      cloned into recombinant baculovirus and the encoded gene products were expressed
      in insect (SF9) cells. The expressed L1 proteins reacted by immunofluorescence
      and immunoprecipitation with polyclonal and monoclonal antibodies generated
      against their corresponding native virions and by Western blotting with
      antibodies that recognized nonconformational epitopes of denatured virions. The
      recombinant L1 proteins expressed conformational epitopes in both cos and Sf9
      cells that were type-specific and displayed neutralizing epitopes. The ability to
      express, purify, and qualitate the reactivity of recombinant L1 proteins will now
      permit the serologic analysis of host response to HPV infection and the
      development of prophylactic PV subunit vaccines.

PMID- 7525427
TI  - The prognostic significance of urinary beta core fragment in premenopausal women
      with carcinoma of the cervix.
AB  - The mortality of premenopausal women with cervical carcinoma has increased in
      recent decades despite attempts to provide screening. The urinary concentration
      of the beta core fragment of hCG has been proposed as a sensitive marker in
      gynecological malignancies, although most studies have not corrected for urine
      concentration. We measured the urinary concentration of beta core and creatinine
      in 61 women who developed cervical cancer premenopausally and expressed the
      concentration of beta core per millimole of creatinine using the 90th percentile
      of a control group as a cutoff level. While correcting for urinary concentration
      results in a reduction in sensitivity of the test (67 to 51%), there is improved
      correlation with prognosis in that after 18 months 81% of women positive for beta
      core had died, while 80% of women negative for beta core were still alive. Of
      those initially presenting and dying there was an increase with increasing stage
      of disease. For patients with initial presentation disease, 11 (79%) of the 14
      patients with elevated levels had died compared with 1 of 21 (5%) who were
      negative for beta core. Urinary beta core fragment may have a major role as a
      prognostic indicator in cervical carcinoma rather than as a screening or
      diagnostic marker and enables identification of patients at higher risk of an
      aggressive disease.

PMID- 7525428
TI  - Skene's gland adenocarcinoma with increased serum level of prostate-specific
      antigen.
AB  - Skene's (periurethral) gland carcinoma is a rare neoplasm accounting for less
      than 0.003% of all genital tract malignancies in females. Generally,
      adenocarcinomas of the female urethra are assumed to arise from the periurethral
      glands, the female homologue of the prostate. A case of Skene's gland
      adenocarcinoma without mucosal urethral involvement is presented. The histologic
      features of this tumor closely resembled those of prostatic adenocarcinoma. In
      contrast, clear cell and columnar/mucinous variants of female urethral
      adenocarcinomas have been described previously. Perhaps this signifies different
      biologic processes in the development of Skene's/periurethral and urethral
      adenocarcinomas in females. Additionally, we performed immunohistochemical
      staining that was reactive for prostate-specific antigen (PSA). Preoperatively,
      the serum level of PSA was increased and promptly decreased after surgical
      excision of the lesion. Therefore, preoperative and postoperative monitoring of
      serum PSA titers in patients with adenocarcinomas of the female urethra or
      periurethral glands (or both) should be considered.

PMID- 7525429
TI  - Study of the enzymatic activity of GGT, LDH, PAP and PSA in semen stains:
      application to age calculation.
AB  - The conditions under which semen stains are stored can markedly affect the
      stability of some of their biochemical parameters. Because of the resistance of
      semen to processes of degradation and denaturation, the age of the stain may,
      under optimum conditions, be calculated. We studied six series of semen stain
      placed on absorbent natural cloth under three different storage temperatures: 5
      degrees C (refrigerator), 18-25 degrees C (room temperature), and 38 degrees C
      (incubator). Seminal fluid was obtained from nonvasectomized and vasectomized
      individuals aged 25-40 years (mean age 30 +/- 0.32 years, SD 3.06). A total of
      240 strains were divided into groups depending on the duration of storage: 24, 48
      or 72 h, 1 week, 1, 2, 4 or 6 months. Eluates were analyzed for gamma
      glutamyltransferase (GGT), lactate dehydrogenase (LDH), prostatic acid
      phosphatase (PAP), and p30 or prostate specific antigen (PSA). The results of
      regression analyses showed that a large proportion of the dependent variable (age
      of the stain) was explained by the rest of the biochemical markers tested.
      Calculation of the age of the semen stain thus requires consideration of several
      biochemical parameters.

PMID- 7525430
TI  - [Interferon or C virus-induced autoimmune chronic hepatitis? Report of personal
      observations and review of the literature].
AB  - Chronic persistent hepatitis C in a 35 year-old man treated for nine months with
      interferon, converted into autoimmune chronic hepatitis. Prior to this
      conversion, the laboratory cell-integrity parameters of C hepatitis had
      permanently returned to normal, and HCV RNA had become negative. Prior to the
      initiation of treatment with interferon, no autoimmune antibodies had been
      present. On the basis of reports in the literature, the possible pathogenesis of
      this conversion is discussed, with two major mechanisms being considered: 1.
      induction of the autoimmune process by interferon, and 2. the "unmasking" of a
      pre-existing autoimmune process in the later course of chronic virus C hepatitis.

PMID- 7525431
TI  - Reduced numbers of CD8+ T cells and B cell-expression of Leu-8 antigen in
      peripheral blood of patients with primary biliary cirrhosis.
AB  - The presence of Leu-8 antigen, the human homologue of the murine MEL-14
      peripheral lymph node homing receptor, defines subsets of peripheral blood
      mononuclear cells (PBMC) with different functions. Since it has been suggested
      that abnormal function of Leu-8 subsets may contribute to the immunopathogenesis
      of primary biliary cirrhosis (PBC), this study was undertaken to define whether
      abnormal expression of the Leu-8 antigen occurs in this disease. We studied 25
      PBC patients, 12 with other chronic liver diseases, and 21 normal controls. PBMC
      were tested by direct immunofluorescence using monoclonal antibodies and flow
      cytometry. In PBC the proportion of PBMC that were CD4+ was normal; in contrast,
      the proportion that were CD8+ was decreased (p < 0.01). A negative correlation
      was found between absolute numbers of CD8+ T cells and total serum bilirubin
      levels (r = -0.50, p < 0.05). The distribution of Leu-8 antigen on T cells was
      normal; however, the proportion of PBMC that were B cells was increased (p <
      0.01) and the fraction of these that were Leu-8 negative was also increased (p <
      0.01). The expression of antigens of activation on B cells was similar to that
      for normal controls. These findings suggest that in peripheral blood of PBC
      patients reduced numbers of T cells may occur due to a selective intrahepatic
      sequestration of CD8+ T cells, and that the decreased expression of Leu-8 antigen
      by B cells may be associated with their participation in autoimmune processes.

PMID- 7525432
TI  - Necrosis of hepatocellular carcinoma caused by spontaneously arising arterial
      thrombus.
AB  - This paper describes a 65-year-old Japanese man with hepatocellular carcinoma
      (HCC) in whom the alpha-fetoprotein level decreased remarkably without any
      treatment. Plain computed tomography disclosed a low-density area in the left
      lateral segment. Liver scintigraphy revealed a filling defect with 99mTc-Sn
      colloid and increased uptake of 67Ga-citrate. The latter was smaller in area than
      the former. This indicates that non-necrotic HCC was still present at this time.
      There was no hypervascular lesion in the hepatic angiogram obtained 22 days after
      liver scintigraphy. The tumor was resected by partial hepatectomy 24 days after
      hepatic angiography. The histological section showed almost complete
      necrotization of the tumor, and the necrotic change consisted of old and recent
      necrosis. An arterial thrombus was formed in non-tumor liver tissue. It was
      presumed that coagulative necrosis was produced by interruption of the blood
      supply due to the spontaneous formation of an arterial thrombus.

PMID- 7525433
TI  - [Studies on expression and function of Eta-1(early T lymphocyte activation-1) in
      autoimmune prone MRL/Mp-lpr/lpr mice].
AB  - The role of CD4-CD8-(double negative; DN) T cells on the polyclonal activation of
      B cells which might lead to autoantibody production and hyper gamma-globulinemia
      was studied in autoimmune-prone MRL/Mp-lpr/lpr mice. The expression of various
      cytokine mRNA in various T cell subsets was examined by using RT-PCR (Reverse
      Transcriptase-Polymerase Chain Reaction) method. CD4+ T cells as well as DNT
      cells constitutively expressed IFN-gamma, TNF-alpha, and TNF-beta genes.
      Importantly IL-3, IL-4, IL-5, or IL-6, which are supposed to stimulate B cell
      activation and differentiation was not expressed by DNT cells. In contrast, DNT
      cells constitutively expressed Eta-1 mRNA. Eta-1 was known to be expressed by
      normal T cells short after the activation and active B cells and macrophages to
      produce polyclonal Ig production. Therefore, in this study, the role of Eta-1 on
      polyclonal B cell activation was studied by using highly purified colostrum Eta
      1. In addition, I found that Eta-1 titer is elevated in serum of MRL/lpr mice but
      not of control mice. Taken together, it is conceivable that in MRL/lpr mice Eta-1
      is produced by DNT cells in vivo and induce polyclonal activation of B cell
      loading to hyper gamma-globulinemia and autoantibody production.

PMID- 7525436
TI  - [Development of synthetic peptide vaccine against influenza--T cell epitope the
      hemagglutinin of A/Aichi/2/68(H3N2) influenza virus induced immune response in
      mice].
AB  - Residues 46 and 54 of a synthetic peptide composed of residues 43-58
      (AEGFSYTDANKNKGIT) of pigeon cytochrome c (p43-58) function as the agretope (the
      site of contact between the major histocompatibility complex and the antigen) and
      residues 50 and 52 function as the epitope (the site of contact between the T
      cell receptor and the peptide antigen). 46F54A peptide which was prepared by
      reserving phenylalanine (F) at an agretopic position 46 but substituting
      asparagine (N) to alanine (A) at the other agretopic position 54 bound to I-Ab
      molecule more tightly than p43-58. Previously, it was demonstrated that F at
      position 46 and A at position 54 functioned as the agretope in the 46F54A
      specific and I-Ab-restricted T cell responses. Then I proved that these
      substitutions of amino acids at the agretopic positions did not affect the
      epitopic function, and substitutions of amino acids at the epitopic positions did
      not affect the binding between the agretope and MHC class II molecule each other.
      In the present study, I synthesized peptide vaccine by introducing several
      peptide fragments deduced from the hemagglutinin (HA) of A/Aichi/2/68 (H3N2)
      influenza virus into the central epitopic part of 46F54A. 46F/HA127-133/54A
      (18mer) which was synthesized by substituting residues 48-52 of 46F54A to
      residues 127-133 of the HA could induce antigen specific proliferative response
      of T cells in I-Ab mice. In the sera obtained from the I-Ab mice immunized
      intraperitoneally with 46F/HA127-133/54A (18mer) specific antibodies to
      A/Aichi/2/68 (H3N2) influenza virus were detected by ELISA. In addition, the sera
      neutralized infectivity of the virus in plaque reduction test using MDCK cells in
      vitro. This synthetic peptide vaccine was incorporated in multi-lamella-liposome
      and administered intranasally to I-Ab mice. The mice were protected from
      challenge infection with A/Aichi/2/68 (H3N2) influenza virus in vivo.

PMID- 7525437
TI  - [Serum granulocyte-colony stimulating factor (G-CSF) levels in elderly patients
      with infections].
AB  - To clarify the clinical role of granulocyte-colony stimulating factor (G-CSF), we
      examined the levels of serum G-CSF in elderly patients with infection (n = 48)
      and elderly normal volunteers (n = 32). G-CSF levels were significantly higher in
      patients in acute infectious status (571.9 +/- 782.9 pg/ml, mean +/- SD) than in
      normal volunteers (25.3 +/- 19.7 pg/ml). There was no significant relationship
      between serum G-CSF levels and age or granulocyte count in normal volunteers. In
      acute infectious status, there was no relationship between serum G-CSF levels and
      granulocyte count or c-reactive protein (CRP). We compared the response of G-CSF
      to infection between patients with frequently repeated infection (repeaters) and
      others (non-repeaters). Repeaters showed relative lower elevation of G-CSF levels
      in acute infectious status compared with non-repeaters (197.6 +/- 370.0 pg/ml vs.
      1014.1 +/- 927.4 pg/ml p < 0.001). In other clinical data, serum albumin was
      significantly lower in repeaters than in non-repeaters. There was no significant
      difference in age, serum total protein, white blood cell count, granulocyte count
      and CRP. In non-repeaters, G-CSF levels was significantly higher in acute phase
      of infection than in recovery phase (550 +/- 703 pg/ml vs. 37.5 +/- 39.2 pg/ml p
      < 0.01 n = 15). We determined the status which showed incomplete recovery of
      infectious symptoms as chronic phase. In twenty-two of repeaters, we examined
      serum G-CSF levels and clinical data in acute and chronic phase of infection.
      There was no significant difference in G-CSF levels between in acute and chronic
      phase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525434
TI  - [Cellular and biological characterization of CD7-positive acute leukemia cells-
      an investigation of the established cell line, HSM911].
AB  - A novel human CD7-positive leukemia cell line (HSM911) derived from the
      peripheral blood of a patient with acute myelogenous leukemia (AML) was studied
      for its cellular and biological characterization. Proliferation assay using a
      variety of cytokines demonstrated that the HSM911 cells proliferate in response
      to recombinant granulocyte-macrophage-colony stimulating factor (rGM-CSF),
      recombinant Interleukin-3 (rIL-3) and recombinant stem cell factor (rSCF), but do
      not in response to recombinant granulocyte-colony stimulating factor (rG-CSF),
      natural macrophage-colony stimulating factor (M-CSF), rIL-1, rIL-2, rIL-4, rIL-5,
      rIL-6 or recombinant erythropoietin (rEpo). Polyclonal anti-GM-CSF antibody and
      polyclonal anti-IL-3 antibody blocked the proliferation of HSM911 stimulated with
      rGM-CSF and rIL-3, respectively. HSM911 maintained in the presence of rGM-CSF
      expressed the CD7, CD13, CD33, CD34, CD41a, HLA-DR, VLA1-VLA5, CD11a, CD54, CD44
      and LAM1. These findings suggest that HSM911 might be of multipotent progenitor
      cell origin. GM-CSF receptors and rIL-3 receptors expressed on this cell line
      were simultaneously suppressed by rGM-CSF or rIL-3, whereas only IL-3 receptors
      were down-modulated by rSCF. Treatment with 12-o-tetradecanoyl-phorbol-13-acetate
      (TPA) induced the differentiation of HSM911 cells into macrophage-like cells but
      not erythroblasts, megakaryocytes or lymphocytes. Interferon-gamma and
      transforming growth factor-beta (TGF-beta) suppressed the proliferation of HSM911
      cells in a dose dependent manner. HSM911 was relatively resistant against anti
      cancer drugs compared with fresh AML cells and other leukemic cell line. HSM911
      is a useful tool for analyzing CD7-positive acute myelogenous leukemia.

PMID- 7525435
TI  - [Molecular mechanism in hematogenous metastasis of pancreas carcinoma--possible
      implication of tumor-derived cytokine in a cell-to-cell interaction of pancreas
      carcinoma and vascular endothelial cells].
AB  - Cellular adhesion between sialyl Lewis a (SLea)-positive pancreas carcinoma and
      endothelial cells is augmented by exogenous cytokines such as interleukin (IL)-1
      beta and tumor necrosis factor (TNF)-alpha through an upregulated E-selectin
      expression on endothelial cells. Preincubation of pancreas carcinoma cells with
      endothelial cells for 4-6 hours at the ratio of 1:10 induced E-selectin
      expression on endothelial cell surface, and dramatically increased subsequent
      attachment of SLea-positive pancreas carcinoma with endothelial cells.
      Paraformaldehyde-fixed PCI cells also induced E-selectin on vascular endothelial
      cells upon direct contact with endothelial cells. Culture supernatants from all
      six pancreas carcinoma cell lines contained soluble, E-selectin-inducible
      factors. Antibodies against SLea and E-selectin but not SLex or ICAM-1 blocked
      the increased pancreas carcinoma-to-endothelial attachment. These findings
      suggested that SLea-positive pancreas carcinoma cells produced E-selectin
      inducing cytokines, both in the soluble and the membrane bound forms, resulted in
      augmented attachment to endothelial cells in vitro. The soluble factor lost its
      activity to induce E-selectin at 70 degrees C, and was different from IL-1-beta
      or TNF-alpha, because the supernatants contained no measurable IL-1 beta and TNF
      alpha. Moreover, pretreatment of the supernatants with specific antibodies to IL
      1 beta and TNF-alpha could not neutralize the E-selectin-inducing activity.
      Instead, all six pancreas carcinoma cell lines produced proteins of IL-1 alpha,
      and preincubation of the supernatant with specific antibody to IL-1 alpha almost
      completely removed the E-selectin-inducing activity from the supernatants. The
      collecting evidence suggests that substances such as IL-1 alpha produced by
      pancreas carcinoma cells may contribute to hematogenous metastasis of cancers in
      non-inflamed distant locations.

PMID- 7525438
TI  - [Definite diagnosis of premature rupture of the membranes (PROM) using intra
      amniotic dye injection method and development of a new kit (AFP-test kit) for
      PROM diagnosis].
AB  - In the diagnosis of premature rupture of the membranes (PROM) in the mid
      trimester of pregnancy, it is often difficult to obtain reliable information from
      only an analysis of the amniotic fluid, especially in equivocal cases. In cases
      where we have not been able to obtain a definite diagnosis of PROM by
      conventional methods including amnioscopy, we have employed the intra-amniotic
      dye injection method (PSP method) by abdominal amniocentesis. We have established
      the method to be good for discrimination of high-leak and low-rupture PROM as
      well as the rupture of the pseudo-amniotic cavity, and have preliminarily
      reported on the clinical usefulness and safety of the PSP method since 1981. In
      this study, through examination of 64 equivocal PROM cases, we have investigated
      the clinical efficacy of the PSP method for cases in their 14th to 33rd week of
      gestation. The conventional methods showed a correct diagnostic rate of 63.9%
      70.5%, in contrast the PSP method had a 100% rate. We have reconfirmed the
      clinical efficacy of the PSP method. The PSP method has been proven to be a
      reliable PROM diagnostic method, but employed for a selected doubtful cases. A
      non-invasive, reliable and rapid method which can be employed in a repeated
      manner as a bed-side examination, has been needed for many years. Amniotic fluid
      contains a high concentration of alpha-fetoprotein(AFP), especially in mid
      trimester, and undetectable levels are determined in urine, vaginal fluid and
      seminal fluid. We have developed a new anti-AFP monoclonal antibody kit for PROM
      diagnosis. In the present study, we investigated the fundamental ability of AFP
      test kit and the clinical efficacy of this kit for 71 cases in their 11th to 40th
      week of gestation with PROM or suspected PROM. The AFP-test kit method showed a
      correct diagnostic rate of 100%. The reaction time of this kit is approximately 3
      minutes. It is a simple and non-invasive test which can be easily carried out
      repeatedly as a bed-side examination. This study has confirmed the high efficacy
      of the AFP-test kit as a method of PROM diagnosis.

PMID- 7525439
TI  - [Study on roles of L-arginine to nitric oxide pathway for the cardiovascular
      control: assessment with a new model of hypertension produced by the chronic
      administration of nitric oxide synthase inhibitor].
AB  - This study was aimed to make a new stable model of chronic hypertension by
      administration of a nitric oxide synthase inhibitor. L-Nw-nitroarginine
      methylester (NAME), and using this model, to investigate the roles of nitric
      oxide for the cardiovascular regulation. Male Wistar rats were implanted of
      osmotic pumps filled with saline (control group: n = 8), 0.2M NAME (low NAME
      group: n = 13) or 1M NAME (high NAME group: n = 12) intraperitoneally. After 4
      week observation of blood pressure (BP) and heart rate (HR), blood concentrations
      of cathecholamine, active renin, L-arginine and L-Nw-nitroarginine were measured
      and histological changes in aorta and heart were examined. Age-matched SHRSP (n =
      9) served as positive controls. BP elevated in the low NAME and high NAME group
      (113.9 +/- 3.1 to 144.0 +/- 4.4 mmHg, and 114.1 +/- 7.3 to 181.4 +/- 9.0 mmHg,
      respectively; mean +/- S.E.), while BP remained constant in the control group and
      SHRSP group (116.8 +/- 5.5 to 120.6 +/- 1.9 mmHg, 200.3 +/- 5.1 to 213.8 +/- 7.4
      mmHg, respectively). HR in the low NAME and high NAME group rapidly decreased
      (not equal to 410 to not equal to 340 bpm) and then slowly returned to the
      control level. HR in the control group and SHRSP group remained constant (not
      equal to 420 and not equal to 450 bpm, respectively). Noradrenaline increased
      significantly in the high NAME group (0.21 +/- 0.03 ng/ml), and there were no
      significant changes in the control, low NAME and SHR group (0.13 +/- 0.02, 0.14
      +/- 0.02, 0.15 +/- 0.03 ng/ml, respectively). Adrenaline, dopamine and active
      renin concentrations did not differ among 4 groups. Aortic wall/lumen area ratio
      in the high NAME group was similar to that in SHRSP group, in spite of its lower
      BP and shorter duration of hypertension compared with SHRSP. Left ventricular
      wall of the high NAME group was significantly thicker than that of SHRSP group.
      These findings suggest that, in addition to endothelium-derived NO, NO produced
      in the brain and peripheral neurons may function to regulate cardiovascular
      system by inhibiting noradrenaline release from sympathetic nerves or by
      inhibiting cardiac and vascular cell proliferation.

PMID- 7525440
TI  - Prolactin and beta-hCG in pregnancy: 24 hour hormone profiles during preterm
      labour and the last 6 hours up to delivery.
AB  - We examined the 24 hour plasma profiles of prolactin and beta-hCG in 7 women with
      preterm labour between the 30th and 34th week of gestation. The results showed
      that, despite preterm labour, the circadian rhythm of prolactin was maintained.
      The beta-hCG levels showed a wide scattering in the normal range which is also
      characteristic of pregnancy with no complications. In addition we examined the
      prolactin and beta-hCG levels during the last 6 hours preceding delivery. Here we
      found significant higher hormone concentrations of hCG in the mothers delivered
      of female babies than in the mothers of males. This higher hormone level declined
      continuously during the delivery, however, without significance. We also observed
      concordant secretion patterns of prolactin and beta-hCG in these cases. Normal
      hCG and prolactin values were found in mothers delivered of male babies.

PMID- 7525444
TI  - Growth factors and ovarian function: the IGF-I paradigm.
AB  - The large body of information now supports the existence of an intraovarian IGF
      system replete with ligands, receptors, and binding proteins. The intraovarian
      IGF system is most likely concerned with the amplification of gonadotropin
      hormonal action, other potential regulatory roles remaining speculative at this
      time. There is every reason to believe that work in this area in the upcoming
      several years will yield new insight necessary to establish whether or not IGFs
      are truly indispensable to ovarian function. At this time, this ultimate
      requirement remains to be demonstrated through selective ablation of ovarian IGF
      I gene expression and the examination of the impact of such manipulation on
      reproductive potential.

PMID- 7525442
TI  - Effect of 5-alpha-reductase inhibition on sex-hormone-binding globulin in elderly
      men.
AB  - In this study we examined the possibility that chronic reduction in serum
      dihydrotestosterone (DHT) attained by pharmacologic inhibition of 5 alpha
      reductase modulates serum sex-hormone-binding globulin (SHBG) levels in elderly
      men. Twenty-one men, ages 58-79 years (mean 66) with benign prostatic hypertrophy
      were treated with the 5 alpha-reductase inhibitor finasteride (5 mg daily) for 12
      months. Serum DHT declined by 80% (p < 0.001) and total testosterone rose by 14%
      (p < 0.05). Serum SHBG concentration remained unchanged (44.1 +/- 4.5 vs 45.2 +/-
      5.7 nmol/l for pre- and post-therapy levels, respectively). Thus, the conversion
      of testosterone to DHT is not required to maintain the androgenic effect on serum
      SHBG concentration in elderly men.

PMID- 7525443
TI  - Role of insulin-like growth factor II and IGF binding proteins in extrapancreatic
      tumor hypoglycemia.
AB  - Serum from patients with extrapancreatic tumor hypoglycemia (EPTH) contains
      elevated levels of big (pro) IGF II which disappears after successful removal of
      the tumor. Nevertheless, total IGF II serum levels are mostly found in the normal
      range both before and after operation. Why then do these patients become
      hypoglycemic? Oversecretion of big IGF II leads to suppression of growth hormone
      (GH). As a consequence, formation of a GH-dependent 150-kD IGF binding protein
      (BP) complex is impaired which normally carries 70-80% of total serum IGF II and
      largely restricts its bioavailability. Impaired formation of the 150-kD complex
      leads to a shift of IGF II to a 50-kD IGFBP complex, resulting in a 30-fold
      shorter serum half-life of IGF II, increased turnover and enhanced
      bioavailability. Insulin target organs are thus exposed to an enormous insulin
      like potential which is continuously provided by oversecreted big IGF II and
      causes increased glucose consumption by skeletal muscle, inhibition of hepatic
      glucose production, inhibition of lipid mobilisation from adipose tissue, and
      pronounced hypoglycemia.

PMID- 7525441
TI  - High molecular weight growth hormone (> 160 kD) in human serum characterized with
      monoclonal antibodies.
AB  - Human growth hormone (hGH) was analyzed by six monoclonal antibodies (Mabs) and a
      polyclonal antiserum (Pas) before and after molecular sieve chromatography of
      sera from healthy subjects. Their hGH levels were between < 0.2 and 0.4 ng/ml as
      determined with Pas. The six Mabs reacted with five distinct epitopes and bound
      to a hGH fragment corresponding to the amino acid sequence 15-125. Two of the
      Mabs showed reduced binding to 20-kD hGH. The binding of Mabs to dimeric forms of
      hGH varied. Human GH levels in unfractionated sera as determined with Mabs were <
      3.1-390 ng/ml. After molecular sieve chromatography of the sera, one peak of hGH
      immunoreactive material of high molecular weight (> 160 kD) and one at the
      elution volume of monomeric hGH were determined with Pas and Mabs. The major part
      of the high molecular weight hGH (> 160 kD) seemed to consist of 22-kD hGH
      molecules, since Pas and all Mabs detected the hGH immunoreactivity (> 160 kD) in
      a similar manner. This high molecular weight hGH (> 160 kD) was distinguishable
      from the identified, receptor-like hGH-binding protein in serum.

PMID- 7525446
TI  - Non-cryopreserved, limited number (1 or 2) peripheral blood progenitor cell
      (PBPC) collections following GCSF administration provide adequate hematologic
      support for high dose chemotherapy.
AB  - Sixty-two patients with a variety of malignant diseases including 44 with breast
      cancer, seven with sarcomas, five with germ cell tumours, four with Hodgkin's
      disease and two with multiple myeloma received short duration, high dose
      chemotherapy, with non-cryporeserved peripheral blood progenitor cell rescue as
      treatment for malignancy. Limited, (one or two) peripheral blood precursor cell
      collections were performed following either cyclophosphamide,
      cyclophosphamide+GCSF or GCSF priming. Total nucleated cell and CD34+ cell yields
      were significantly higher with either of the two GCSF priming regimens as
      compared to cyclophosphamide only priming. Cell viability at the time or
      reinfusion was also enhanced by GCSF priming. Chemotherapy regimens included
      either high dose cyclophosphamide, mitoxantrone and VP16 (HD-CNV); high dose
      melphelan plus VP16; high dose BCNU, cyclophosphamide and VP16 (BCV); or high
      carboplatin, cyclophosphamide and VP16 (PCV) all given over 8-12 h. Non
      cryopreserved blood progenitor cells, stored at 4 degrees C, were reinfused 24 h
      after completion of chemotherapy. Sixty-one of 62 patients showed hematologic
      recovery. Median time to hematologic recovery was significantly shorter for
      patients receiving GCSF primed cell collections. There was also significantly
      less hospitalization and antibiotic usage for patients receiving GCSF primed
      precursor cell collections. The addition of post chemotherapy GCSF did not,
      however, appear to enhance the rate of hematologic recovery. This study shows
      that simplified schedules for high dose chemotherapy administration together with
      simple precursor cell collection procedures provide safe and effective methods
      for administering myeloablative chemotherapy treatment.

PMID- 7525447
TI  - Recent progress in multiple myeloma.
AB  - Multiple myeloma is recognized as a neoplasm of phenotypically mature plasma
      cells which produces a variety of clinical symptoms related both to tumour
      infiltration of the bone marrow and cytokine production. The latter results in
      bone disease and a complex interactive network between plasma cells, marrow
      stromal cells and other hematopoietic cells. This serves to sustain the myeloma
      proliferative pool and promote maturation and secretion of monoclonal
      immunoglobulin. Whereas the recognizable tumour cells in myeloma are the most
      mature B cells, early lymphoid cells are involved in the disease and probably
      represent the proliferative pre-plasma cell compartment. The definition of the
      myeloma 'stem cell' remains controversial, but our understanding of early pre
      plasma cell differentiation in multiple myeloma has been aided by studies on
      normal non-neoplastic equivalents. Techniques like high resolution flow
      cytometry, flow cytometric DNA analysis and improvements in our ability to obtain
      karyotypic data in multiple myeloma will improve our understanding of myeloma
      cell biology, hopefully yielding new prognostic information. Finally,
      improvements in assessing prognosis will help identify patients whose survival
      with standard therapy is limited and who may require innovative or aggressive
      treatment protocols. These individuals must be separated from patients who either
      require no initial therapy or who are likely to have good outcomes with standard
      approaches.

PMID- 7525445
TI  - Insulin-like growth factors, insulin-like growth factor binding proteins and
      ovarian androgen production.
AB  - Increasing evidence indicates that the ovary contains an insulin-like growth
      factor (IGF) system complete with ligands, binding proteins, and receptors.
      Through their interaction with IGF receptors on theca-interstitial cell surface
      membranes, the ligands, IGF-I and IGF-II, synergize with luteinizing hormone (LH)
      to increase ovarian androgen production. The actions of these growth factors are
      modulated by intraovarian binding proteins, especially IGFBP-1, IGFBP-2, and
      IGFBP-3, that enhance or inhibit the biological actions of the IGFs. These
      observations suggest that the IGF system plays a role in normal ovarian function
      and in the pathophysiology of ovarian hyperandrogenism and polycystic ovary
      syndrome.

PMID- 7525448
TI  - Induction of eosinophilic granules, nonspecific esterase activity and CD14
      expression in the human eosinophilic leukemia cell line, EOL-1.
AB  - We examined the expression of eosinophilic granules, esterase activity and CD14
      in a human eosinophilic cell line, EoL-1. Unstimulated EoL-1 cells were weakly
      positive for nonspecific esterase, but negative for surface CD14, and contained a
      few eosinophilic granule-positive cells. A combination of G-CSF and TNF-alpha
      increased the eosinophilic granule-containing cells, but failed to increase
      esterase activity or CD14 expression. IFN-gamma alone or in combination with TNF
      alpha enhanced nonspecific esterase activity but failed to induce CD14 expression
      or increase eosinophilic granule-containing cells. dbcAMP increased eosinophilic
      granule-containing cells, nonspecific esterase activity and CD14 expression.
      Specific esterase activity was not detected in any circumstances. EoL-1 cells
      fractionated by density gradients or CD14 expression showed nonspecific esterase
      activity and CD14 expression in both the eosinophilic granule-positive and
      negative cell populations. Forskolin and butyrate had a synergistic effect on
      CD14 induction and protein kinase A was suggested to play a role in dbcAMP
      induced CD14 expression. A protein kinase C activator, phorbol 12-myristate 13
      acetate, did not increase eosinophilic granules, nonspecific esterase activity or
      CD14 expression in EoL-1 cells. The results show that EoL-1 cells can express
      nonspecific esterase and CD14, but the expression is not necessarily restricted
      to cells which have differentiated into the monocyte/macrophage lineage.

PMID- 7525449
TI  - Cytokeratin expression and distribution in adamantinoma of the long bones and
      osteofibrous dysplasia of tibia and fibula. An immunohistochemical study
      correlated to histogenesis.
AB  - Twenty-four cases of adamantinoma and 24 cases of osteofibrous dysplasia of the
      long bones were studied to evaluate the expression and distribution of
      cytokeratin (CK) subtypes in relation to histogenesis and differentiation. The
      immunohistochemical study was performed on tissue fixed in buffered formalin and
      embedded in paraffin wax utilizing antibodies to vimentin, factor VIII,
      epithelial membrane antigen and cytokeratins of different molecular weights. In
      all cases the vimentin antibody marked positively in stroma, endothelium and
      osteoblasts, while factor VIII expression was confined to endothelial cells. In
      71% of adamantinomas, vimentin showed strong immunoreactivity in the tumour cells
      of nests and tubules. CKAE1/AE3 and CK19 were strongly expressed in all
      morphological patterns of adamantinoma emphasizing their epithelial origin, while
      the antibodies to CK8 and CK18 showed a high percentage of negative responses. In
      osteofibrous dysplasia the epithelial-like component was much smaller than in
      adamantinoma and was present in scattered islands composed of a few cell positive
      for CKAE1/AE3 and CK19 and negative for other keratins. These results suggest
      that these two lesions are of a similar histogenesis.

PMID- 7525451
TI  - Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster.
AB  - Genetic polymorphisms in leukocyte and endothelial cell adhesion molecules may be
      important variables with regard to susceptibility to multifactorial disease
      processes that include an inflammatory component. For this reason, polymorphisms
      were sought for intercellular adhesion molecule-1 (ICAM-1; gene symbol ICAM1) and
      for the three genes in the selectin cluster, P-selectin, L-selectin, and E
      selectin (gene symbols SELP, SELL, and SELE, respectively). Two amino acid
      polymorphisms were identified for ICAM-1; Gly or Arg at codon 241 and Lys or Glu
      at codon 469. Dinucleotide repeat polymorphisms were identified in the 3'
      untranslated region for ICAM-1 and in intron 9 for P-selectin. Restriction
      fragment length polymorphisms were found using cDNAs for each of the three
      selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L
      selectin with HincII. Linkage analysis was performed for the selectin gene
      cluster and for ICAM-1 using the CEPH families; ICAM-1 is very tightly linked to
      the LDL receptor on chromosome 19, and the selectin cluster is linked to markers
      at chromosome 1q23.

PMID- 7525450
TI  - Detection of more than 50 different CFTR mutations in a large group of German
      cystic fibrosis patients.
AB  - We have conducted a comprehensive study of the molecular basis of cystic fibrosis
      (CF) in 350 German CF patients. A screening approach based on single-strand
      conformation analysis and direct sequencing of genomic polymerase chain reaction
      products has allowed us to detect the molecular defects on 95.4% of the CF
      chromosomes within the coding region and splice sites of the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene. The spectrum of sequence changes
      comprises 54 different mutations, including 17 missense mutations, 14 nonsense
      mutations, 11 frameshift mutations, 10 splice site variants and two amino acid
      deletions. Eleven of these mutations have not previously been described. Our
      results reflect the marked mutational heterogeneity of CF in a large sample of
      patients from a non-isolated population.

PMID- 7525454
TI  - Audiovisual teaching: an alternative learning strategy.

PMID- 7525453
TI  - Modeling of intraluminal heating of biological tissue: implications for treatment
      of benign prostatic hyperplasia.
AB  - A computer model for predicting the thermal response of a biological tissue to
      different intraluminal heating modalities is presented. A practical application
      of the model is to calculate the temperature distributions during thermal
      coagulation of prostate by contact heating and radiative heating. The model uses
      a two-dimensional axisymmetric diffusion approximation method to calculate the
      light distribution during radiative heating. The traditional Pennes' bio-heat
      equation is used to calculate the temperatures in the presence of blood flow. An
      implicit finite difference scheme with nonuniform grid spacings is used to solve
      the diffusion equation for light distribution and the bio-heat equation. Model
      results indicate that the radiative heating of prostate by Nd:YAG (1064 mm) and
      diode (810 mm) lasers can be a more effective and efficient means of coagulating
      a large volume of prostate, as compared to contact heating of the tissue. Blood
      perfusion is shown to provide a considerable heat sink as the laser exposure time
      is increased. Surface cooling by irrigation during the laser irradiation of
      tissue is shown to be an effective method for delaying tissue explosion and
      obtaining a large volume of coagulated tissue. The model also shows that the
      volume of the coagulated tissue is appreciably altered by a change in the rate of
      energy deposition.

PMID- 7525455
TI  - Normal vibrations and valence charge distribution in relation to bioactivity of
      gammexane.
AB  - Normal coordinate analysis has been made for gammexane using the Wilson's G-F
      matrix method with Urey-Bradley force field. Molecular orbital calculations using
      CNDO/2 method have also been carried out for the five isomers of
      hexachlorocyclohexane to give the valence charge densities on the atoms of the
      molecules. A toxicity parameter that takes into account a shape factor and the
      valence charge density on the atoms has been defined. On the toxicity scale so
      defined the gamma-isomer alone has a significant value.

PMID- 7525452
TI  - Identification of two clusters of mouse insulin-like growth factor binding
      protein genes on chromosomes 1 and 11.
AB  - The genes for insulin-like growth factor binding proteins (IGFBPs) encode
      secreted proteins that bind insulin-like growth factors I and II with high
      affinity and modulate their biological activities. In this report we have used
      interspecific backcross mapping and gene cloning to define the chromosomal
      locations of 4 mouse Igfbp genes. Igfbp1 and 3 are found in the proximal part of
      chromosome 1. In the human genome these two loci map within 20 kb of one another
      on chromosome 7p14-p12, and the genes are organized in a tail-to-tail
      configuration. Mouse Igfbp2 and 5 colocalize to a proximal region of chromosome 1
      that is syntenic with human chromosome 2q33-q36, and the two genes are 5 kb apart
      in a tail-to-tail orientation. These results suggest an evolutionary scheme in
      which a primordial IGFBP gene duplicated to form a cluster that was later
      replicated to create second linkage group.

PMID- 7525456
TI  - [Chemoimmunotherapy of malignancies of the gastrointestinal tract].
AB  - Stimulation of the immune response could be obtained in outpatients with
      inoperable locally advanced or metastasizing gastrointestinal tumors (n = 56),
      who were palliatively treated with cyclophosphamide (cy), 350 mg/m2 i.v.,
      thymostimulin, echinacin i.m. and in part additionally with epirubicin, 15 mg/m2
      i.v. At present, outpatients with pancreatic (n = 7) or colon carcinomas (n = 1)
      receive interleukin 2 (IL-2) intralesionally, 2 x 10(5) Cetus units (CU), days 3,
      5 and 7 after cy, and by portable continuous infusion systems i.v., 3 x 10(5)
      CU/day, days 3-8 after cy. Subsets of lymphocytes slightly decreased in the
      patients' peripheral blood, recall antigen reactivity slightly increased.
      Patients' mean survival time was 5.7 +/- 1.7 months.

PMID- 7525457
TI  - [Expression of the OKM5 antigen (CD36) in normal keratinocytes and inflamed
      mucosa].
AB  - In 62 oral mucosa biopsies of different localization and diagnoses,
      immunohistochemically investigated with the APAAP technique, the OKM5 expression
      on keratinocytes was connected with the epithelial keratinization. In
      parakeratotic epithelia, an obvious CD36 upregulation was detectable.
      Surprisingly, there was no correlation between neither the state of inflammation
      nor the diagnoses and the OKM5 keratinocyte expression; the oral localization by
      itself appeared to be responsible for the CD36 expression.

PMID- 7525458
TI  - Analysis of a naturally occurring HLA class I-restricted viral epitope.
AB  - A previously described nonapeptide sequence motif for antigens recognized by T
      cells in the context of the human major histocompatibility complex (MHC) molecule
      HLA-A2.1 was used to identify the natural epitope of influenza A virus matrix
      protein. We show here that the peptide with the sequence GILGFVFTL is the
      synthetic analogue of the natural epitope by demonstrating the presence of the
      corresponding peptide on MHC molecules of virus-infected cells. The role of the
      hydrophobic anchor amino acids in positions 2 and 9, which constitute the epitope
      motif, was investigated with synthetic variants of the epitope and cytotoxic T
      lymphocytes as indicator cells. The crucial role of the side chains of amino
      acids in those positions was evidence by their influence on the efficiency of T
      cell stimulation.

PMID- 7525459
TI  - Peptide specificity and HLA restriction do not dictate lymphokine production by
      allergen-specific T-lymphocyte clones.
AB  - Human and murine CD4+ T lymphocytes can be subdivided into distinct subsets [T
      helper type 0 (Th0), Th1 or Th2], based on their lymphokine production profiles.
      Not much is known about the factors that determine these restricted lymphokine
      secretion profiles. Peptide specificity and human leucocyte antigen (HLA)
      restriction may be such factors. As it is well established that allergen-specific
      T lymphocytes from atopic individuals and non-atopic controls differ in their
      lymphokine secretion profile, we studied two allergen-specific T-lymphocyte
      clones (TLC) with identical peptide specificity and HLA restriction that were
      generated from the peripheral blood of an atopic donor and a non-atopic control
      donor. The two CD4+ TLC recognize the same epitope (20-33) of the house dust mite
      Dermatophagoides pteronyssinus major allergen Der p II. Both TLC recognize the
      epitope in an HLA-DQB1*0602-restricted manner. However, the lymphokine production
      profiles of these TLC show clear differences after allergen-specific or
      polyclonal activation. As expected, TLC JBD4 from the atopic donor produced high
      levels of interleukin-4 (IL-4) without detectable interferon-gamma (IFN-gamma),
      whereas TLC PBA1 from the non-atopic donor produced both IFN-gamma and IL-4 upon
      allergen-specific or polyclonal activation. Inasmuch as both TLC recognized the
      same epitope of Der p II in association with the same HLA-DQ molecule, these data
      suggest that peptide specificity and HLA restriction of human allergen-specific
      TLC do not dictate their lymphokine secretion profile.

PMID- 7525462
TI  - A study of CD45RO, CD45RA and CD29 antigen expression on human decidual T cells
      in an early stage of pregnancy.
AB  - The decidua is the place where the fertilized egg is implanted and where the
      immunocompetent cells of the mother come into direct contact with genetically
      disparate cells of the conceptus. Although the T cells in the decidua are exposed
      to fetal antigens, the fetus is not rejected by maternal immunocompetent cells.
      In the present study, we examined surface markers to determine whether the T
      cells in the human decidua are naive T cells without or memory T cells with a
      history of antigen stimulation. Although few T cells were present in the decidua,
      as compared to the peripheral blood, CD45RO+, CD29+ and CD45RA- CD4+ T cells as
      well as CD45RO+, CD29+ and CD45RA- CD8+ T cells, which are considered to be
      memory T cells, were in the majority, with only small numbers of CD45RO-, CD29-
      and CD45RA+ CD4+ and CD8+ cells, which are naive T cells, present. Also, the
      decidual mononuclear cells secreted IL-2 and IL-4. Since IL-4 is secreted only by
      memory T cells, it is suggested that in the decidua memory T cells increase in
      number and secrete cytokines, thereby in some way influencing the phenomenon of
      fertility.

PMID- 7525460
TI  - Interleukin-8 and RANTES induce the adhesion of the human basophilic cell line KU
      812 to human endothelial cell monolayers.
AB  - Basophils are implicated in the pathogenesis of the late-phase allergic reaction,
      but the mechanisms by which circulating basophils adhere to vascular endothelium
      and migrate to lesional sites remain unclear. In order to assess the biological
      similarity of the basophilic cell line KU-812 to normal human basophils, we have
      compared the adhesion response of this cell line and normal basophils, following
      challenge with interleukin-8 (IL-8) and RANTES. We demonstrate here that IL-8 and
      RANTES are able to stimulate the adherence of the basophilic cell line, KU-812,
      to cytokine-activated human umbilical vein endothelium (HUVEC). The chemokine
      induced increase in adhesion was dose-related and was maximal after prior priming
      with IL-5. The stimulation of adhesion was partially inhibited by co-incubation
      with anti-CD18 and anti-CD11c antibodies and antibodies to the beta 1-integrins.
      In comparison, the chemokine-induced adhesion of normal human basophils was only
      inhibited by the beta 2-integrins. These chemokines were also able to induce the
      migration of KU-812 in a dose-dependent manner, but only after prior treatment
      with phorbol myristate acetate (PMA) or IL-5. In all cases tested, IL-8 was more
      potent and efficacious than RANTES. We conclude from these studies that these
      members of the chemokine superfamily may play an important role in the
      recruitment of reactive leukocytes in allergic inflammation, by stimulating their
      adhesion and subsequent migration from the vasculature into the inflammatory
      sites. However, it is apparent that KU-812 is not an adequate substitute for
      normal human basophils in order to investigate chemokine biology.

PMID- 7525463
TI  - Aging. Polymorphism, compartmentalization and environmental impact.
AB  - The proportion of elderly in our population is steadily increasing and so is the
      need to provide sophisticated health care. We must intensify research which
      provides results, leading to the design of preventive medicine, before the
      increased proportion of aged causes a crisis in our health care and social
      systems. The potential impact of such research represents the best and most cost
      effective means of preparing for the future, and providing directions for a
      better quality of life with reduced chronic and debilitating illness for the
      elderly. Indeed, prevention appears to be the only approach able to lower the
      enormous economic burden of the cost of geriatric medicine [1,2]. There are many
      precedents in medical research for preventive measures being much more cost
      effective than therapeutic means: one of them is immunization against
      poliomyelitis as an alternative to development of improved models of iron lungs.

PMID- 7525461
TI  - Human blood contains two subsets of dendritic cells, one immunologically mature
      and the other immature.
AB  - Two subsets of dendritic cells, differing in T-cell stimulatory function, have
      been purified directly from human blood. Both subsets are positive for major
      histocompatibility complex (MHC) class II expression and negative for lineage
      specific antigens (e.g. CD3, CD14, CD16, CD19 negative), but are separated by
      exploiting differences in expression of the beta 2-integrin, CD11c. The CD11c
      negative subset is functionally immature, requiring monocyte-derived cytokines to
      develop into typical dendritic cells. The CD11c-positive subset has potent T-cell
      stimulating activity and expresses the activation antigen CD45RO, unlike its
      immature counterpart. However, these mature cells only develop typical dendritic
      morphology and high levels of MHC proteins and adhesins after a period of culture
      independent of exogenous cytokines. Although the freshly isolated mature
      dendritic cells resemble monocytes in cytospin preparations, the former lack CD14
      and have a much stronger primary T-cell stimulatory capacity. We hypothesize that
      the CD11c-negative immature cells are marrow-derived precursors to tissue
      dendritic cells, such as epidermal Langerhans' cells, while the CD11c-positive
      cells are derived from tissues where they have been activated by antigen, and are
      en route to the spleen or lymph nodes to stimulate T-cell responses there.

PMID- 7525464
TI  - Aging: the cellular immune response against autologous and foreign antigens is
      affected before the humoral response.
AB  - In this study we examined the auto- and hetero-immune response in mice of
      different ages immunized with antigens of Trypanosoma cruzi (S-105). We observed
      that 20-day- and 12-month-old mice showed decreased response to foreign antigens
      and increased response to autoantigens, compared with 3-month-old immunized mice.
      The 6-month-old mice showed hetero- and auto-immune cellular responses similar to
      those of 12-month-old animals; however, the humoral response was similar to that
      of 3-month-old animals against either antigen, suggesting that the compartments
      of the immune response are altered at different moments in the same individual.
      Immune response against a foreign antigen is correlated with the presence of
      cellular infiltrate in skeletal and heart muscle whereas no modifications in the
      tissue are noticed in animals with an autoimmune response. Also, we observed from
      cell transfer experiments that lymph node cells are involved in the dysregulation
      that we noticed with aging.

PMID- 7525466
TI  - Grafting of a hepatitis B S-preS(2) T-cell epitope on lysozyme enhances the
      immunogenicity of lysozyme in responder mice primed with the T-cell epitope.
AB  - Subunit immunogens composed of well-defined T- and B-cell epitopes might
      represent a valuable approach to design vaccines. The reduction of the size of
      the T-cell epitope is clearly in the line of this strategy. In this study we
      evaluated the capacity of a hepatitis B S-preS(2) surface antigen-derived T-cell
      epitope (i.e., S2b) to enhance the humoral immune response towards lysozyme when
      covalently linked to this antigen. We hereby anticipated that new problems,
      related to processing of a subunit immunogen, may emerge when grafting
      minimalized T-cell epitopes on protein antigens. Indeed, insertion of a T-cell
      epitope containing peptide (i.e., S2b) in a new protein context does not warrant
      a correct processing of the T-cell epitope. To avoid such potential processing
      problems an acid labile linker between T-cell and B-cell epitopes was devised in
      order to provide a processing-independent cleavage site. Using a T-cell hybridoma
      specific for the S2b T-cell epitope the S2bC-lysozyme conjugate was found to be
      presented by functional antigen-presenting cells. However, fixed APC did not
      present the conjugate in vitro indicating that processing is required for the
      release and presentation of S2b. The ability of the conjugate to generate an
      enhanced immune response was investigated in vivo. In S2b-primed mice the S2bC
      lysozyme conjugate was found to elicit a faster and higher anti-lysozyme humoral
      response, as compared to uncoupled mixtures of lysozyme and S2b.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7525465
TI  - Does the age-related change in CD44-defined T-cell subsets have functional
      significance for cytotoxic T lymphocyte generation?
AB  - CD44 or Pgp-1 is a transmembrane leukocyte adhesion-related glycoprotein which is
      often expressed in greater density on the membranes of memory T lymphocytes
      (CD44hi) compared to naive T cells (CD44lo). The proportion of Pgphi or CD44hi
      cells among T cells is increased with advancing age. We examined the relevance of
      this alteration for the age-related decrease in the generation of allospecific
      CTL activity. The findings confirm the age-related increase in the frequency of
      CD44hi cells in spleens of aged mice of several strains, but also show
      interstrain variability in the magnitude of the increase (bm1 > C57BL/6 >
      BALB/c). In contrast, we found that after allo-stimulation, the proportion of
      cells bearing the memory phenotype is decreased in cells from aged mice,
      particularly within the CD8+ T cell subset. To determine if these observations
      reflected an alteration in the frequency or responsiveness of naive T cells,
      enriched populations of spleen cells depleted of CD44hi cells were prepared from
      spleen cells of young and aged mice, and stimulated in mixed lymphocyte culture.
      Enrichment for cells expressing the naive phenotype did not restore the ability
      of T cells from aged mice to generate allospecific CTL. Together, these findings
      suggest that (1) the age-related increase in frequency of splenic T cells
      expressing memory phenotype and concordant decrease in phenotypically naive
      cells, does not explain the age-related decrease in the ability to generate
      primary allo-CTL, and (2) naive cells from aged mice exhibit intrinsically
      compromised ability to generate CTL in response to primary alloantigenic
      stimulation.

PMID- 7525467
TI  - Human thymic epithelial cells in serum-free culture: changes in cytokine
      production in primary and successive culture periods.
AB  - Human thymic epithelial cells (TEC) have been cultured in a growth factor-defined
      serum-free medium, and their production of cytokines in primary cultures and
      during three subsequent culture periods was investigated. TEC produced
      interleukin (IL)-1 alpha, IL-6, and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) in all culture periods, as detected by the use of ELISA and B9
      cell assay. The highest concentrations of the cytokines were found in the
      tertiary and quaternary subculture period, but in these subcultures the
      production decreased progressively. There was no clear correlation between cell
      proliferation and cytokine production in the cultures.

PMID- 7525468
TI  - Monoclonal antibodies against antigenic epitopes common between Setaria cervi and
      Brugia malayi.
AB  - Several common antigens between the bovine (Setaria cervi) and human (Brugia
      malayi) filarial parasites have been demonstrated [Immunol Investig, 16 (1987)
      139]. Hybridoma cell lines producing monoclonal antibodies against such common
      antigenic epitopes were obtained by immunizing the BALB/c mice with S. cervi
      antigen, fusing the spleen cells with Sp2/0 myeloma cells and screening the
      culture supernatants for antibody against both S. cervi and B. malayi antigens by
      ELISA. Nine monoclonal antibodies directed against antigenic epitopes common
      between the bovine and human filarial parasites were identified. Two monoclonal
      antibodies (I3B4 and I5D6) showed reactivity with the antigen(s) present in
      filariasis patients serum and thus may have potential for detecting circulating
      antigen in filaria infected individuals.

PMID- 7525469
TI  - Characterization of antigenic determinants on porcine zona pellucida-3 beta(ZP3
      beta) glycoprotein by monoclonal antibodies.
AB  - Out of 11 monoclonal antibodies(MAbs) developed against porcine zona pellucida-3
      beta(ZP3 beta) glycoprotein, 6 (MA-451, -454, -455, -462, -467 and -470) reacted
      with ZP2 beta, deglycosylated ZP3 beta(DGZP3 beta), and reduced and
      carboxyamidomethylated ZP3 beta(RCMZP3 beta) in ELISA and Western blot suggesting
      that these monoclonals recognise a linear protein epitope. Five MAbs(MA-452, 
      456, -459, -474 and -476) showed reduced binding with DGZP3 beta and RCMZP3 beta
      as compared to ZP3 beta in ELISA suggesting that these may recognize either
      carbohydrate moities or conformation dependent epitopes. Moreover, these MAbs
      failed to recognize these antigens on Western blot. Based on competitive
      inhibition studies in ELISA for the ability of MAbs to inhibit the binding of
      biotinylated ZP3 beta to solid phase antibody, 6 distinct domains were
      discernible. Domain V recognised by MA-467 partially overlaps with the domain
      corresponding to MA-454 and MA-455. All 11 MAbs reacted with zona pellucida of
      intact oocytes as revealed by indirect immunofluorescence but only 3 antibodies
      (MA-454, -455 and -467) delayed the zona lysis by trypsin. In immunoblots MA-467
      recognised 18kDa fragment of RCMZP3 beta digested with endoproteinase lys-C and
      37 and 30kDa bands of elastase digest of ZP3 beta. The results will help in
      delineation of functionally relevant domains and design of contraceptive vaccine
      based on zona pellucida aiming for pre-fertilization block.

PMID- 7525472
TI  - B-1 cells in systemic autoimmune responses: IgM+, Fc epsilon Rdull B cells are
      lost during chronic graft-versus-host disease but not in murine AIDS or collagen
      induced arthritis.
AB  - The potential role of B-1 cells (i.e. the CD5+ B cell and "sister" B cell
      subsets) in autoimmunity is controversial. CD5+ B cells have been shown to
      secrete antibodies of similar specificity as those found in many systemic
      autoimmune diseases; in addition, increases in CD5+ B cell frequency have been
      reported in patients suffering from rheumatoid arthritis, Sjogren's syndrome,
      myasthenia gravis, insulin-dependent diabetes mellitus and Hashimoto's
      thyroiditis. Whether these increases are due to expansion of B-1 lineage cells in
      the human or due to activation-induced expression of CD5 by conventional B cells
      is unclear. In the present study, we used three murine models of systemic
      autoimmunity: murine acquired immunodeficiency syndrome (MAIDS), chronic graft
      versus-host disease (cGvHD), and collagen-induced arthritis (CIA) to determine
      whether increases in B-1 cell frequency are universally seen in models of
      autoimmunity which are mechanistically distinct. In contrast to the
      aforementioned human systemic autoimmune diseases which exhibit an increase in
      CD5+ B cell frequency, the percentage of CD5+ B cells declined in all three
      murine models of systemic autoimmune disease. Even though there was a decrease in
      the frequency of CD5+ B cells there was no change in the actual number of CD5+ B
      cells. Thus, the apparent decline in CD5+ B cell frequency was due to increases
      in either T cells, conventional Fc epsilon R+ B cells, or both. The only actual
      decline in a B cell subset was the loss of IgM+, Fc epsilon Rdull cells in both
      the spleen and peritoneal cavity of mice undergoing a chronic graft-versus-host
      reaction. Therefore, our data suggests that expansion of the B-1 subset does not
      occur as a general feature of murine systemic autoimmune disease. These
      observations, consistent with previous studies of Ig gene usage in autoreactive
      antibodies, support the view that expansion and differentiation of the CD5+ B
      cell subset is not a central event leading to autoantibody production.

PMID- 7525470
TI  - C4 gene polymorphism in primates: evolution, generation, and Chido and Rodgers
      antigenicity.
AB  - Eleven new C4d genomic primate sequences of the fourth complement factor (C4)
      have been obtained. Seven of them belong to five species not yet explored for
      this gene: Pan paniscus (pygmy chimpanzee), Cercopithecus aethiops (green
      monkey), Macaca mulatta (rhesus monkey), Macaca fascicularis (cynomolgus), and
      Saguinus oedipus (cotton top tamarin). The New World monkeys (tamarins, four
      individuals) sequenced for C4 have a single C4d sequence only, which shows a B
      isotypic specificity and a Rodgers 3 (Rg3), Chido 1 (Ch1) antigenicity. Rg3 and
      Ch1 could thus be the oldest Rg/Ch specificity (at least 50 million years old)
      and Rg1, Rg2, Ch3, and Ch6 could be more recent human-specific antigens.
      Mechanisms of C4d polymorphism generation were analyzed by compiling all the
      presently available sequences. Examples of both point mutations and crossing-over
      events among C4d primate sequences could be detected. The problem of a possible
      trans-species inheritance of C4d polymorphism was addressed and two apparently
      contradicting dendrograms were obtained. One of them, constructed by using both
      exon and intron sequences, does not support trans-species evolution, but supports
      the proposed theory of extensive homogenization of the C4 genes occurring within
      each species, because alleles from each primate species cluster together. Another
      completely different dendrogram, obtained by using exon sequences only, suggests
      the existence of trans-species evolution for C4d polymorphism, because alleles
      belonging to different species cluster together in a way similar to that found
      for HLA class I or II alleles. However, orangutan sequences group together in
      both kinds of C4d sequence dendrograms and seem to have arisen from an ancestor
      different from that of chimpanzee, gorilla and man C4d sequences. Finally,
      further data have been obtained that support trans-species conservation of A-ness
      and B-ness and the existence of trans-specifically conserved allelic motifs, both
      in intronic and exonic sequences.

PMID- 7525471
TI  - Expression of CD44 variant transcripts in dog lymphatic tissue.
AB  - The gene of the CD44 cell surface glycoprotein consists of 20 exons. Ten exons
      known as variant exons are inserted by alternative RNA splicing between exon 5
      and 16, thus generating diversity in the extracellular portion of the protein. We
      have cloned the dog cDNA homologue of the human variant exon region of CD44 and
      characterized its transcript expression in normal lymphatic tissues. Using PCR
      with primers complementary to regions contiguous to the insertion point and a
      variant exon, all ten variant exons of dog CD44 were detected in a high number of
      different isoforms. Transcripts containing the ten variable exons directly
      spliced to both sides of the insertion point were detected. We found an extensive
      usage of all variant exons from v1 to v10 in a high number of different
      combinations, some presenting a tissue-specific expression pattern. A similar
      complex profile of transcript expression was found in peripheral blood
      lymphocytes from rat and human.

PMID- 7525473
TI  - Failure of presented, non-dominant self epitope to induce tolerance: implications
      for autoimmune diseases.
AB  - It has been observed that a hierarchy exists among epitopes such that fewer
      epitopes are actually involved in the induction of T cell response and tolerance
      than there are epitopes available in a given antigen. Some epitopes which are
      "cryptic" for immune activity within the protein, are nevertheless able to elicit
      a response if administered alone and can also be used to by-pass tolerance. We
      report that tolerance to a self protein shows the same phenomenon seen for non
      self proteins. In fact, we elicit a proliferative response toward a predicted
      minor cryptic epitope, to which animals are clearly not self-tolerant. The minor
      epitope escapes the induction of tolerance to self proteins more easily than the
      major epitopes, since we cannot elicit proliferative response to the major
      epitope. A striking feature of our results however is that lack of self tolerance
      to the minor epitope appears as not being due to the failure of presentation of
      this epitope in normal, healthy animals.

PMID- 7525474
TI  - Hematological status of beta-thalassemics in Madras.
AB  - Although rapid technical advances have taken place in the diagnosis of beta
      thalassemia, still the hematological factors were found to be suitable screening
      test in areas like Indian subcontinent where a high prevalence of beta
      thalassemia trait was observed. Among various thalassemias reported in Asian
      Indians, beta-thalassemia account for about 80% and is responsible for very high
      infantile mortality. Despite this, little is known about the hematological status
      of beta-thalassemias among this ethnic group which is associated with more than
      five different predominant beta-globin mutation with high frequency and variable
      number of rare ones. The present study is the first report of hematological
      status of beta-thalassemia among this ethnic group particularly from Tamil Nadu,
      Southern India, who are still practising high degree of consanguinity. In the
      present study, a total number of 364 beta-thalassemics were investigated. This
      includes 84 cases of homozygous beta-thalassemias and the remaining 280 were
      heterozygotes. The hematological factors such as red cell indices, hemoglobin F
      and hemoglobin A2 were assessed. The results revealed a wide spectrum of
      hematological variables ranging from severe form as that of Mediterranean
      thalassemias to very mild form of anemia as that of African Negro population.

PMID- 7525475
TI  - Teaching epidemiology of acute diarrheal diseases to medical undergraduates--a
      new approach.
AB  - A total of 165 students of first clinical year were taught the epidemiology of
      acute diarrheal diseases, during three successive years using a detailed lesson
      plan. The usual didactic lecture was minimised and supplemented by slide shows,
      and transparencies based on the contents of a handout on the subject distributed
      to all students a day prior to the class. This was followed by participatory
      discussions by the students on the diagnosis and management of some case examples
      presented. A video clip summarising the entire lesson was screened for
      reinforcement. Feed-back from the students showed that the teaching methodology
      was rated very good by 41%, and satisfactory by 59%. While 73% of the students
      mentioned videoclips as a factor favouring their learning, 69% cited the handouts
      and 49% felt that case discussions were helpful. Objective evaluation of the
      performance in the sessional test showed that out of 158 students who attended
      the test, 75% scored above 50% marks, 21% below 50% and the remaining 4% did not
      attempt that question.

PMID- 7525476
TI  - Tissular expression and regulation of type 1 angiotensin II receptor subtypes by
      quantitative reverse transcriptase-polymerase chain reaction analysis.
AB  - Recent studies have revealed that angiotensin II (Ang II) interacts with two
      pharmacologically different types of seven-transmembrane domain receptors, hence
      named Ang II type 1 and type 2 (AT1 and AT2) receptors. cDNAs for the AT1
      receptor have been cloned, and the existence of two receptor subtypes, AT1A and
      AT1B, has been revealed in rat and mouse. This study presents a new approach for
      the specific quantification of AT1A and AT1B receptor mRNAs by reverse
      transcription and polymerase chain reaction amplification in the presence of an
      AT1 receptor mutant cRNA as internal standard. Absolute quantities of mRNA are
      then determined by extrapolation using the standard curve generated with the
      internal standard. Moreover, addition of this internal standard to each tube
      controls for both reverse transcription and polymerase chain reaction
      amplification in each sample. In male Wistar rats, the highest absolute AT1A
      receptor mRNA levels were found in liver and kidney and those for AT1B receptor
      mRNA in the pituitary. Expressed as a percentage of total AT1A+AT1B receptor mRNA
      content, AT1A receptor mRNA content was 100% in liver, 85% in lung, 73% in
      kidney, 65% in aorta, 48% in adrenals, and 15% in the hypophysis. Since this
      approach can determine absolute AT1A and AT1B receptor mRNA quantities in
      different organs, it allows the study of the regulation of their expression under
      different pathophysiological conditions. After sodium depletion, known to induce
      hyperactivity of the renin-angiotensin system, adrenal AT1A and AT1B receptor
      mRNA levels were increased by 60% and 110%, respectively. In contrast, in
      renovascular hypertension (two-kidney, one clip), also associated with elevated
      circulating plasma renin activity, adrenal AT1B receptor mRNA levels decreased by
      50%, whereas there was no change in those of AT1A. Therefore, the differential
      distribution and regulation of these two receptor subtypes suggest that each of
      them might be involved in the mediation of different biological effects of Ang
      II.

PMID- 7525477
TI  - Roles for protein kinases in the induction of nitric oxide synthase in
      astrocytes.
AB  - Lipopolysaccharide (LPS) or a combination of interferon (IFN)-gamma and
      interleukin (IL)-1 beta can induce a calcium-independent nitric oxide synthase
      (iNOS) in astrocyte cultures (Simmons and Murphy: J Neurochem 59:897, 1992; Eur J
      Neurosci 5:825, 1993; Galea et al: Proc Natl Acad Sci USA 89:10945, 1992). This
      induction can be measured by assaying cyclic GMP levels in the cultures, which
      correlates with, but is more sensitive than, measurement of nitrite accumulation.
      To study potential second-messenger systems involved in the induction of iNOS,
      phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, and
      various protein kinase inhibitors were employed. PMA induced a time-, dose-, and
      L-arginine-dependent increase in cyclic GMP, which could be inhibited by
      dexamethasone or actinomycin D. This induction could be dramatically increased by
      concurrent treatment with IFN-gamma. The presence of iNOS mRNA could be
      demonstrated by hybridization with a specific cDNA probe. H7 (a non-specific
      serine/threonine kinase inhibitor) but not H89 (a more specific PKA inhibitor)
      prevented induction by all agents. However, downregulation of PKC or pretreatment
      with the PKC inhibitor calphostin C did not prevent the induction by LPS or
      cytokines, suggesting that PKC is not necessary for iNOS induction by these
      mediators. Additionally, genistein (a nonspecific tyrosine kinase inhibitor)
      could prevent induction by all agents, but the more specific inhibitor,
      tyrphostin, attenuated only NOS induction by LPS. These results suggest that
      activation of PKC can lead to, but is not necessary for, the induction of NOS in
      astrocytes and that there is a potential role for tyrosine kinases in NOS
      induction by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525478
TI  - Induction of type III-deiodinase activity in astroglial cells by retinoids.
AB  - Thyroid hormones and retinoic acid (RA) are important modulators of growth,
      development, and differentiation. Type III deiodinase (D-III), which catalyzes
      thyroid hormones degradation in the brain and in cultured astroglial cells, is
      induced in astroglial cells by multiple pathways, including cAMP, 12.0
      tetradecanoylphorbol-13-acetate (TPA), fibroblast growth factors, and thyroid
      hormones themselves. In the present study, the effects of retinoids on D-III
      activity were examined in astroglial cells cultures in a chemically defined
      medium devoid of hormones and growth factors. Incubation of astroglial cells with
      5 microM all-trans-RA caused up to 200-fold increase in D-III activity, which
      reached a plateau after 48 h. The retinoid-induced increase in D-III activity was
      concentration dependent (0.5 microM all-trans-RA and 9-cis-RA producing half
      maximal effect). Retinol was effective at physiological concentrations (1 and 10
      microM). The 48 h effects of 5 microM all-trans-RA and 10 nM thyroid hormones on
      D-III activity were at least additive. Addition of 2 nM acidic fibroblast growth
      factor or 1 mM 8-bromo-cAMP for the last 8 h of a 48 h incubation with 5 microM
      all-trans-RA did not alter the induction by all-trans-RA, whereas 0.1 microM TPA
      in the same conditions produced an additive effect with all-trans-RA. All-trans
      RA (5 microM) had little or no effect on type II deiodinase, the enzyme which
      catalyzes the activation of thyroxine to 3,5,3'-triiodothyronine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7525479
TI  - Mobilization of intracellular calcium by substance P in a human astrocytoma cell
      line (U-373 MG).
AB  - Variations in intracellular free calcium concentration (delta[Ca2+]i) were
      measured in intact and isolated human astrocytoma cells (U373 MG) loaded with
      fura-2 acetoxymethylester. Microperfusion of 50 nM substance P (SP), applied for
      1 s, increased [Ca2+]i by 351 nM from a stable basal level of [Ca2+]i of 26 nM.
      The peak delta[Ca2+]i induced by SP was dose dependent with a threshold of 10(-3)
      nM, an ED50 of 1.3 nM and a maximal effect for concentrations of SP greater than
      100 nM. The NK1 receptor agonist, [Sar9Met(O2)11]SP, mimicked the effect of SP,
      while the NK2 and NK3 selective receptor agonists, [N1(10)]NKA(4-10) and
      senktide, respectively, had no effect. The delta[Ca2+]i induced by SP was
      unaffected by 100 microM cadmium or by removal of extracellular calcium ions.
      Caffeine up to 30 mM had no effect on [Ca2+]i. In contrast, thapsigargin
      increased resting [Ca2+]i by 92 nM and reduced the delta[Ca2+]i induced by SP. A
      pertussis treatment (500 ng/ml-24 h) did not modify the delta[Ca2+]i induced by
      SP. We conclude that SP, acting on a NK1 receptor, mobilizes cytosolic calcium
      from an intracellular calcium pool which can be partially depleted by
      thapsigargin.

PMID- 7525480
TI  - Bacterial endotoxin induces [Ca2+]i transients and changes the organization of
      actin in microglia.
AB  - We have employed amoeboid microglia purified from primary cultures of neonatal
      rat brain to examine the effect of bacterial lipopolysaccharide (LPS), a potent
      activator of immune cells, on intracellular calcium concentration ([Ca2+]i) in
      brain macrophages. In single brain macrophages loaded with indo 1, pulse
      administration of LPS elicited a rapid and transient increase in [Ca2+]i. From a
      total of 70 cells examined, all responded to LPS with a similar [Ca2+]i
      transient, indicating a good homogeneity of the cell population with regard to
      the LPS response. It was concluded that the rise of cytosolic [Ca2+]i originated
      from intracellular stores because the response to LPS occurred similarly in the
      presence or in the absence of extracellular Ca2+. A second administration of LPS
      to the same cells resulted in a second but reduced [Ca2+]i transient. In contrast
      to the first response to LPS, this second response was totally dependent on the
      presence of Ca2+ in the extracellular medium. The first response to LPS was
      strongly inhibited by ruthenium red and could be suppressed in a reversible
      manner by preincubating the cells with caffeine in the absence of Ca2+ in the
      extracellular medium. These results indicate that caffeine-sensitive
      intracellular Ca2+ stores may be the major source of Ca2+ in the response of
      brain macrophages to LPS. The possible release of Ca2+ from
      phosphatidylinositol(3,4,5)-trisphosphate (IP3)-sensitive stores in brain
      macrophages was also evaluated by stimulating cells with the IP3-mobilizing
      agonist histamine. Brain macrophages were heterogeneous with regard to the
      histamine response since histamine induced a [Ca2+]i rise in only 30% of cells
      examined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525482
TI  - Adherence of Pseudomonas aeruginosa and Candida albicans to glycosphingolipid
      (Asialo-GM1) receptors is achieved by a conserved receptor-binding domain present
      on their adhesins.
AB  - Pseudomonas aeruginosa, a gram-negative bacterium, and Candida albicans, a
      dimorphic yeast, are evolutionarily distant microorganisms which can utilize
      filamentous structures termed pili and fimbriae, respectively, to mediate
      adherence to glycosphingolipids (asialoganglioside-GM1) receptors. The mechanism
      of adherence to glycosphingolipid receptors was investigated in these studies. By
      using monoclonal antibodies (MAbs) against purified pili of P. aeruginosa PAK
      (PK99H) and monospecific anti-peptide antibodies against the PAK pilin peptides
      [anti-PAK(128-144) and anti-PAK(134-140)], we demonstrated that these antibodies
      agglutinated C. albicans whole cells and cross-reacted with C. albicans fimbriae
      in immunoblots. A control MAb, PKL1, and anti-PAK(75-84) peptide antibodies
      failed to agglutinate C. albicans whole cells or cross-react with the fimbrial
      proteins. Conversely, the anti-C. albicans fimbrial MAb Fm16, but not Fm34,
      agglutinated P. aeruginosa PAK whole cells and Western blots (immunoblots). The
      interactions between PK99H and Fm16 and their respective homologous antigens were
      competitively inhibited by heterologous antigens; this demonstrated that the
      interactions between the antibodies and the heterologous antigens, i.e., PK99H
      with C. albicans fimbriae and Fm16 with P. aeruginosa pili, were highly specific
      and suggested that both adhesins share a common antigenic determinant. The
      immunological cross-reactivity between Fm16 and P. aeruginosa PAK pilin is
      localized onto the PAK(134-140) region as shown by a competitive enzyme-linked
      immunosorbent assay. The PAK(134-140) region of PAK pilin contains the epitope
      recognized by PK99H and also constitutes part of the receptor-binding domain of
      the pilus adhesin. Thus, the results from these studies suggest that common cell
      surface receptors are recognized by the P. aeruginosa and C. albicans adhesins
      because of a conserved receptor-binding domain on the adhesins.

PMID- 7525483
TI  - T-cell determinants and antibody binding sites on the major mycobacterial
      secretory protein MPB59 of Mycobacterium bovis.
AB  - Among the first proteins encountered by the host immune system upon infection or
      vaccination with mycobacteria are those secreted by the bacillus during growth.
      The antigen 85 complex of Mycobacterium bovis bacillus Calmette-Guerin (BCG) is
      composed of three closely related members. The mature 85B protein of M. bovis
      (MPB59) has a high degree of amino acid identity with the M. bovis 85A protein
      (76%) and the Mycobacterium tuberculosis 85B (99%) and 85A (76%) proteins. We
      have examined the regions of MPB59 which stimulate human T- and B-cell responses
      by use of a set of 28 synthetic peptides, 20 amino acids (aa) in length and
      overlapping by 10 aa. Initial proliferative assays with recombinant MPB59
      demonstrated that peripheral blood mononuclear cells from 95% of BCG vaccinees
      and 52% of tuberculosis patients responded to the whole mature protein.
      Peripheral blood mononuclear cells from MPB59 responders, but not nonresponders,
      were stimulated by peptides in a dose-dependent fashion. Five peptides were
      reactive in more than half of the MPB59 responders. The T-cell-reactive regions
      were essentially identical in the M. bovis and M. tuberculosis 85B proteins.
      Subjects with a variety of HLA-DR phenotypes responded to a number of these
      peptides. The dominant T-cell-reactive regions were distinct from the peptides
      recognized by sera from tuberculosis patients (aa 71 to 100) and the murine
      monoclonal antibody HYT27 (aa 61 to 90). The region reactive with antibodies
      overlapped part of the MPB59 sequence recently shown to participate in the
      binding of MPB59 to fibronectin.

PMID- 7525484
TI  - Mapping of multiple HLA class II-restricted T-cell epitopes of the mycobacterial
      70-kilodalton heat shock protein.
AB  - By combining a DNA subclone and synthetic-peptide approach, we mapped epitopes of
      the immunogenic mycobacterial 70-kDa heat shock protein (HSP70) recognized by
      human CD4+ T-cell clones and lines. In addition, we identified the respective HLA
      DR molecules used in antigen presentation. The donor groups used were healthy
      persons immunized with killed Mycobacterium leprae and tuberculoid leprosy
      patients. The results show that the N-terminal part of the HSP70 molecule
      contains three different T-cell epitopes, of which two were presented by DR7
      (amino acids [aa] 66 to 82 and 210 to 226) and one was presented by DR3 (aa 262
      to 274). The C-terminal part contains one epitope (aa 413 to 424) presented by
      HLA-DR2. The C-terminal epitope shows extensive homology to the corresponding
      region of the human HSP70 sequence. All of the T-cell epitopes identified were
      presented by only one particular HLA-DR molecule. We also found that HLA-DR5 and
      DRw53 can present HSP70 to T cells, demonstrating the presence of additional
      epitopes not yet defined at the peptide level. On the basis of the donors used in
      this study, recognition of HSP70 at the epitope level seems to be ruled by the
      restriction elements expressed by the donor rather than by any difference in
      reactivity between healthy individuals and patients. In conclusion, mycobacterial
      HSP70 is relevant to subunit vaccine design since it contains a variety of T-cell
      epitopes presented in the context of multiple HLA-DR molecules.

PMID- 7525485
TI  - Aeromonas salmonicida resistance to complement-mediated killing.
AB  - The resistance of Aeromonas salmonicida to complement-mediated killing was
      investigated by using different strains and their isogenic mutants that had been
      previously characterized for their surface components. We found that the
      classical complement pathway is involved in serum killing of susceptible A.
      salmonicida strains, while the alternative complement pathway seems not to be
      involved. All of the A. salmonicida strains are able to activate complement, but
      the smooth strains (with or without the A-layer) are resistant to complement
      mediated killing. The reasons for this resistance are that C3b may be bound far
      from the cell membrane and that it is rapidly degraded; therefore, the lytic
      final complex C5b-9 (membrane attack complex) is not formed. Isogenic rough
      mutants are serum sensitive because they bind more C3b than the smooth strains,
      and if C3b is not completely degraded, then the lytic complex (C5b-9) is formed.

PMID- 7525486
TI  - Diverse Lyme disease spirochetes bind integrin alpha IIb beta 3 on human
      platelets.
AB  - Lyme disease is a chronic, multisystemic infection caused by Borrelia burgdorferi
      sensu lato. An infectious strain of B. burgdorferi was previously shown to bind
      to human platelets via the integrin alpha IIb beta 3. In this study, a diverse
      group of Lyme disease spirochetes was tested for platelet- and alpha IIb beta 3
      binding activity. This collection included representatives of each of the three
      species that cause Lyme disease, B. burgdorferi (sensu stricto), B. garinii, and
      B. afzelii. Strains were characterized for infectivity in mouse models or were
      low-passage isolates from human patients. Each of the 11 infectious strains bound
      to platelets immobilized in microtiter wells and in suspension. Binding to
      platelets in suspension was specifically inhibited by a blocking anti-alpha IIb
      beta 3 antibody, and representatives of each species bound to purified alpha IIb
      beta 3. The strains that did not bind alpha IIb beta 3 or platelets were all
      noninfectious. No obvious relationship was observed between binding to platelets
      and expression of the bacterial outer surface protein OspA, OspB, or OspC, as
      assessed by immunoblotting. These results demonstrate that integrin alpha IIb
      beta 3-binding activity is widespread among the Borrelia species that cause Lyme
      disease and are consistent with a role for alpha IIb beta 3 binding in the
      transmission and/or pathogenesis of Lyme disease.

PMID- 7525487
TI  - Role of YadA in arthritogenicity of Yersinia enterocolitica serotype O:8:
      experimental studies with rats.
AB  - Outer membrane protein YadA, the Yersinia adhesin, is one of the plasmid-encoded
      virulence factors of yersiniae. To evaluate the role of YadA in the pathogenesis
      of reactive arthritis experimentally, we used YadA- strain YeO8-116, a kanamycin
      GenBlock insertion mutant derived from Yersinia enterocolitica O:8 wild-type
      strain 8081. As control strains, a plasmid-cured derivative (8081-c) of 8081 and
      a YopH- mutant (8081-yoph) were used. In addition, YeO8-116, with the yadA
      mutation transcomplemented with plasmid pMW10, was used. YeO8-116 induced
      arthritis to a considerably lesser extent than did wild-type strain 8081 when
      inoculated intravenously into Lewis rats. In rats surviving for over 14 days
      after the bacterial inoculation, the arthritis incidences were 6% (4 of 72) among
      those inoculated with the yadA mutant and 51% (33 of 65) among those inoculated
      with wild-type strain 8081. When the yadA gene was transcomplemented back to YeO8
      116, YeO8-116/pMW10 induced arthritis in 47% (9 of 19) of the inoculated rats.
      Plasmid-cured strain 8081-c did not induce arthritis in any of the 24 inoculated
      rats, whereas YopH- mutant 8081-yoph induced arthritis in 20% (5 of 25) of the
      rats inoculated. Although the 50% lethal dose of YeO8-116 was about sixfold
      higher than that of 8081, the kinetics of bacterial elimination from the spleen
      and mesenteric lymph nodes were about the same with both strains. Antibody
      responses in rats infected with the two strains were also indistinguishable. Our
      results indicate that YadA contributes to the arthritogenicity of Y.
      enterocolitica in the rat model.

PMID- 7525481
TI  - Effects of cytokines and periodontopathic bacteria on the leukocyte function
      associated antigen 1/intercellular adhesion molecule 1 pathway in gingival
      fibroblasts in adult periodontitis.
AB  - We investigated the effects of inflammatory cytokines and periodontopathic
      bacteria on expression of intercellular adhesion molecule 1 (ICAM-1), vascular
      cell adhesion molecule 1, and E-selectin (endothelial leukocyte adhesion molecule
      1) in cultured human gingival fibroblasts (HGF). Cell surface ICAM-1 was
      upregulated on HGF under transcriptional control by exposure not only to
      interleukin-1 beta, tumor necrosis factor alpha, and gamma interferon but also to
      sonic extracts prepared from Porphyromonas gingivalis and Prevotella intermedia
      (nigrescens) and lipopolysaccharides from Escherichia coli. However, these
      stimuli induced only minimal expression of vascular cell adhesion molecule 1 and
      E-selectin on HGF. Binding assays using HGF and Molt 4, the human T-cell leukemia
      cell line, showed induced ICAM-1 to be functional, and the increased binding was
      blocked by a combination of monoclonal antibodies against ICAM-1 and leukocyte
      function-associated antigen 1. Furthermore, gingival tissues from adult
      periodontitis patients showed increased mRNA expression of ICAM-1 compared with
      that in tissues from normal healthy donors. In immunohistological analysis, we
      also observed in vivo that the expression of ICAM-1 on fibroblasts in adult
      periodontitis tissues was greater than that in normal gingiva. Thus, the
      overexpression of ICAM-1 on gingival fibroblasts induced by cytokines and
      periodontopathic bacteria is speculated to be deeply involved in the accumulation
      and retention of leukocyte function-associated antigen 1-bearing leukocytes in
      adult periodontitis lesions.

PMID- 7525489
TI  - Dissociation of immune determinants of outer membrane proteins of Chlamydia
      psittaci strain guinea pig inclusion conjunctivitis.
AB  - Chlamydia trachomatis is an important human pathogen. Research to develop a
      Chlamydia vaccine has focused on the major outer membrane protein (MOMP).
      Determinants of this protein elicit serovar-specific neutralizing antibodies
      which are thought to play a critical role in protective immunity. MOMP-specific
      antibody responses are highly variable in the polymorphic population. Genetic
      factors which might influence the MOMP-specific immune response are consequently
      of particular interest. The C. psittaci strain guinea pig inclusion
      conjunctivitis (GPIC) is a natural pathogen of the guinea pig that causes both
      ocular and genital tract infections that closely resemble those caused by C.
      trachomatis in humans. As such, it provides an excellent model for disease. In
      this report, we explore the influence of major histocompatibility complex-linked
      genes on the MOMP-specific antibody response in mice immunized with either whole
      GPIC elementary bodies or recombinant GPIC MOMP. Our results indicate that the
      MOMP-specific antibody response is major histocompatibility complex linked such
      that mice of the H-2d haplotype are high responders while mice of the H-2k
      haplotype are low responders. We demonstrate that MOMP-specific B cells are
      present in H-2k strains which are, however, deficient in MOMP-specific helper T
      cells. Although immunization of low-MOMP-responder strains with whole chlamydial
      elementary bodies induces high levels of immunoglobulin G antibody specific for
      Omp2, the cysteine-rich outer membrane protein, MOMP-specific B cells are unable
      to receive help from Omp2-specific T cells. The failure of intermolecular help
      from Omp2-specific T cells and related observations raise important issues
      regarding the processing and presentation of chlamydial antigens and the design
      of optimal subunit vaccines.

PMID- 7525490
TI  - Antibody response to a Babesia bigemina rhoptry-associated protein 1 surface
      exposed and neutralization-sensitive epitope in immune cattle.
AB  - Protective immunity against Babesia bigemina is hypothesized to involve
      antibodies directed against merozoite surface-exposed epitopes. Levels of
      antibody against a rhoptry-associated protein 1 (RAP-1) B-lymphocyte epitope,
      defined by surface-reactive and inhibitory monoclonal antibodies, in immune
      cattle sera were determined. All cattle produced antibodies to the epitope;
      however, there was limited correlation between immune protection induced by
      infection or RAP-1 immunization and the level of antibody to the neutralization
      sensitive B-lymphocyte epitope examined.

PMID- 7525488
TI  - An HLA-DRw53-restricted T-cell epitope from a novel Mycobacterium leprae protein
      antigen important to the human memory T-cell repertoire against M. leprae.
AB  - Cellular immunity mediated by T cells plays a major role in protection against
      intracellular infections, including leprosy, a chronic disease caused by
      Mycobacterium leprae. In this work, we describe CD4+ T-cell clones, isolated from
      healthy humans immunized with M. leprae, which recognize a novel M. leprae
      protein antigen previously isolated from a lambda gt11 DNA expression library. On
      the basis of the deduced primary structure of the carboxyl-terminal part of the
      antigen, we have used a synthetic-peptide approach to exactly define the T-cell
      epitope recognized. Importantly, major histocompatibility complex restriction
      studies showed that the epitope is presented by an HLA-DRw53 molecule which is
      frequently expressed in many populations. In addition, we have demonstrated that
      a long-term cell-mediated immunity response against the peptide epitope is
      present after immunization with M. leprae. In conclusion, the M. leprae T-cell
      epitope described here fulfills the primary criteria for subunit vaccine
      candidates against leprosy.

PMID- 7525491
TI  - Critical residues of the Mycobacterium leprae LSR recombinant protein
      discriminate clinical activity in erythema nodosum leprosum reactions.
AB  - We reported earlier (S. Singh, N. P. Shanker Narayan, P. J. Jenner, G. Ramu, M.
      J. Colston, H. K. Prasad, and I. Nath, Infect. Immun. 62:86-90, 1994) that
      polyclonal antibodies directed against selective sequences in the Mycobacterium
      leprae recombinant protein designated LSR were present in lepromatous leprosy
      patients undergoing erythema nodosum leprosum (ENL) reactions (type 2 reactions).
      In this study using peptides with single-residue deletions from positions 6 to
      24, we define three distinct regions, GVTY, NAA, and RGD, which were important
      for antibody recognition and for the discrimination of clinically silent and
      active ENL reactions. Antibodies against NAA were found only in patients
      undergoing active reactions. This is in contrast to the results for the RGD
      motif, which was recognized in all ENL patients, irrespective of the clinical
      status. Though GVTY was recognized in both groups of patients, its recognition
      was masked by the flanking glutamic acid. These findings point towards a specific
      molecular recognition pattern that emerges when a lepromatous leprosy patient
      undergoes immune perturbations leading to ENL reactions. Moreover, the fine
      specificity of immunological recognition changes during the natural evolution of
      the host-parasite interaction.

PMID- 7525492
TI  - Vascular endothelial growth factor and glioma angiogenesis: coordinate induction
      of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory
      mechanisms.
AB  - We have previously suggested that tumor angiogenesis in human gliomas is
      regulated by a paracrine mechanism involving vascular endothelial growth factor
      (VEGF) and flt-1 (VEGF-receptor 1). VEGF, an endothelial-cell-specific mitogen,
      is abundantly expressed in glioma cells which reside along necrotic areas,
      whereas flt-1, a tyrosine-kinase receptor for VEGF, is expressed in tumor
      endothelial cells, but not in endothelial cells in normal adult brain. Recently,
      a second tyrosine-kinase receptor which binds VEGF with high affinity, designated
      KDR or flk-1, has been described. We performed in situ hybridization for VEGF
      mRNA, flt-1 mRNA and KDR mRNA on serial sections of normal brain, low-grade and
      high-grade glioma specimens. We show that KDR mRNA is co-expressed with flt-1 in
      vascular cells in glioblastoma but not in low-grade glioma. Since flt-1 and KDR
      are not expressed in endothelial cells in the normal adult brain, the coordinate
      up-regulation of 2 receptors for VEGF appears to be a critical event which
      controls tumor angiogenesis. Immunocytochemistry with a monoclonal anti-VEGF
      antibody revealed significant amounts of VEGF protein in the same glioma cells
      that expressed VEGF mRNA. The largest amount of VEGF immunoreactivity, however,
      was detected on the vasculature of glioblastomas, the site where VEGF exerts its
      biological functions. These findings suggest that VEGF is produced and secreted
      by glioma cells and acts on tumor endothelial cells which express VEGF receptors.
      To further characterize VEGF-producer cells in vivo, we investigated cellular
      proliferation, immunoreactivity to the p53 tumor-suppressor gene product and
      epidermal-growth-factor-receptor (EGFR) expression on serial sections by
      immunocytochemistry. VEGF-producer cells did not show increased cellular
      proliferation, p53 immunoreactivity or EGFR immunoreactivity as compared with
      glioma cells which did not express VEGF. Our studies therefore do not demonstrate
      evidence for a growth advantage of VEGF-producer cells in vivo or VEGF induction
      by p53 mutation or EGFR over-expression.

PMID- 7525494
TI  - Correlation between cytopathological results and in situ hybridisation on needle
      aspiration biopsies of suspected African Burkitt's lymphomas.
AB  - Burkitt's lymphoma (BL) is a very high-incidence malignancy in sub-Saharan
      Africa, where it targets mainly young children. This lymphoma is closely
      associated with Epstein-Barr virus (EBV). Diagnosis of BL relies on clinical
      presentation as well as histological results obtained from biopsies. In this
      report, 66 new patients from Malawi (one of the southernmost African countries
      with high-incidence BL), suspected on clinical grounds to present with BL, had
      fine needle aspiration biopsies taken, smeared on slides and used for May
      Grunwald Giemsa staining. Duplicate slides were independently assessed for EBV
      presence and expression by DNA-DNA and/or RNA-RNA in situ hybridisation (ISH),
      using respectively the repetitive viral BamHIW DNA fragment in a biotinylated
      probe and the small EBV-encoded RNA EBER I in a digoxigenin-labelled riboprobe.
      There was very good correlation between the various techniques in the diagnosis
      of the lymphomas, showing 67% of clinically suspect cases to be BL. Our report,
      presenting data on BL in Malawi, illustrates the usefulness of a simple
      aspiration biopsy in the diagnosis of this malignancy by Giemsa staining and also
      in both types of ISH.

PMID- 7525495
TI  - The fibronectin isoform containing the ED-B oncofetal domain: a marker of
      angiogenesis.
AB  - Different fibronectin (FN) isoforms are generated by the alternative splicing of
      3 regions (ED-A, ED-B and IIICS) of the primary transcript. The FN isoform
      containing the ED-B sequence, a complete type-III-homology repeat, while having
      extremely restricted distribution in normal adult tissues, reveals high
      expression in fetal and tumor tissues. Using the monoclonal antibody (MAb) BC-I,
      specific for the FN isoform containing the ED-B sequence (B+.FN), we demonstrated
      here, using immunohistochemical techniques, that while this FN isoform is
      undetectable in mature vessels, it is highly expressed during angiogenesis both
      in neoplastic and in normal tissues, as in the case of the functional layer of
      endometrium during the proliferative phase. B+.FN is thus a marker for the
      formation of new vessels, and the BC-I MAb may be a useful reagent for evaluating
      the level of the angiogenetic process in different neoplasms.

PMID- 7525493
TI  - Interclonal heterogeneity in a human epithelioid-sarcoma cell line (GRU-1).
AB  - Three clonal sub-populations, GRU-IA, GRU-IB, and GRU-IC, isolated from the human
      epithelioid sarcoma cell line GRU-I, were characterized morphologically,
      cytogenetically and with regard to proliferation kinetics. Immunocytochemically,
      major differences became evident in the expression of cytokeratin 18 and
      neurofilament proteins, which are indicative for epithelial and neural
      differentiation respectively. Vimentin, a mesenchymal differentiation marker,
      however, could be detected in all tumor cells of each sub-population. Laminin, a
      major compound of basement membranes, formed abundant intercellular network-like
      patterns in GRU-IB and GRU-IC, whereas GRU-IA was characterized by a diffuse
      intracellular reaction, suggesting a disorder in laminin secretion.
      Cytogenetically, all sub-populations proved to be DNA-aneuploid, the DNA index
      ranging from 1.4 to 1.5. Proliferation analysis revealed doubling times ranging
      from 13 (GRU-IC) to 19 hr (GRU-IA). These strictly defined clonal sub-populations
      provide a valuable tool for further investigations of the biological behavior of
      human epithelioid sarcoma with special regard to tumor heterogeneity.

PMID- 7525496
TI  - Identification of a novel neutralization epitope on envelope gp46 antigen of
      human T-cell-leukemia virus-type-II (HTLV-II).
AB  - Having observed that multiple neutralization epitopes of human T-cell-leukemia
      virus-type-I (HTLV-I) envelope gp46 clustered in a region between amino acids 187
      and 199, we speculated that a region of HTLV-II gp46 corresponding to the HTLV-I
      neutralization region may contain HTLV-II-specific neutralization epitopes. To
      test this, we immunized a NZW rabbit and BALB/c mice with a synthetic peptide
      containing the HTLV-II gp46 amino acids 182 to 199 (pep182-199) conjugated to
      OVA. The serum from the rabbit reacted to the HTLV-II gp46 and neutralized HTLV
      II-mediated syncytium formation. One monoclonal antibody (MAb), M2E186N1,
      generated from the BALB/c mice, stained specifically the surface of HTLV-II
      positive cells and reacted with HTLV-II gp46 by Western blot. This MAb was of the
      IgA isotype and inhibited HTLV-II- but not HTLV-I-mediated syncytium formation at
      a final antibody concentration of 200 micrograms/ml; it also neutralized an HTLV
      II-VSV pseudotype virus specifically. Epitope mapping by ELISA using overlapping
      synthetic peptides indicated that the neutralization epitope recognized by the
      M2E186N1 MAb was located between HTLV-II gp46 amino acids 186 and 192,
      corresponding to the sequence Leu-Gln-His-Val-Ile-Leu-Gln-Pro. These new
      observations will be helpful in developing vaccines against HTLV-II infection.

PMID- 7525497
TI  - Tumor cells suppress cytokine-induced nitric-oxide (NO) production in cerebral
      endothelial cells.
AB  - Nitric oxide (NO) produced by endothelial cells (EC) has been shown to exert
      cytotoxic activity on tumor cells. In order to analyze events involved in brain
      metastasis, the modulation of NO production in rat-brain-derived EC was
      investigated. NO release was increased by tumor necrosis factor-alpha (TNF
      alpha), interferon-gamma (IFN-gamma), interleukin-1 beta, lipopolysaccharide or
      forskolin in EC219 cells, a rat-brain-microvessel-derived EC line. Dexamethasone
      decreased NO release by cytokine-activated EC219 cells. Tumor cells
      (DHD/K12/PROb, a rat colon-carcinoma cell line) were highly adherent to EC219
      cells, and adhesion was not modified by TNF-alpha plus IFN-gamma, or by
      dexamethasone. Addition of tumor cells or tumor-cell-conditioned medium
      significantly inhibited NO release induced by any of the stimuli examined, but
      only if added during the initial phase of endothelial-cell activation. Tumor
      derived suppression of NO release was also observed in primary cultures of
      cerebral EC. NO synthase (NOS) activity in cytosol extracts of the cerebral EC
      line was Ca(2+)-independent and required both NADPH and tetrahydrobiopterin. NOS
      activity was increased by TNF-alpha and IFN-gamma, and significantly reduced by
      tumor-cell-conditioned medium. These results suggest that rat colon-carcinoma
      cells may have developed a protective mechanism involving the release of (a)
      soluble factor(s) which inhibit(s) NO production by cerebral EC.

PMID- 7525500
TI  - Indocyanine green videoangiography for the imaging of choroidal
      neovascularization associated with macular degeneration.

PMID- 7525498
TI  - Assessment of infant and early childhood development in a periurban Bolivian
      population.

PMID- 7525501
TI  - Prognostic value of beta human chorionic gonadotrophin in blood serum of patients
      with urinary bladder tumours.
AB  - Beta human chorionic gonadotrophin levels have been assessed in blood serum of 79
      patients with bladder tumours before and seven days after transurethral
      electroresection (TUR). With the growth grade of anaplasia and staging the mean
      serum beta HCG level increased. Beta HCG was a good biological marker to
      differentiate between superficial and deep tumours.

PMID- 7525499
TI  - Red blood cell aggregation and microcirculation in rat cremaster muscle.
AB  - Using intravital microscopy of the rat cremaster muscle, we studied the effects
      of changing red blood cell (RBC) aggregation on RBC arteriolar velocity and
      perfused capillary density (PCD). To modify RBC aggregation, 2 and/or 10% dextran
      (molecular weights 40,000, 70,000 or 480,000) or fresh rat plasma was infused
      into adult male rats via a normovolemic hemodilution procedure. The high
      molecular-weight dextrans (70,000 and 480,000) both induced RBC hyperaggregation
      associated with similar dose-dependent decreases in RBC arteriolar velocity (30
      and 40% for dextran concentrations of 2 and 10%, respectively) and in PCD (35 and
      37%, respectively, for the two concentrations). Conversely, with 40,000 molecular
      weight dextran or plasma, we observed a 30% increase in RBC arteriolar velocity,
      but no change in PCD or hyperaggregation. Intravenous injection of the
      antiaggregating drug troxerutin (10(-3) M), either before or after 2% dextran
      70,000, significantly inhibited the effects of this dextran on RBC arteriolar
      velocity and on PCD. We conclude that RBC hyperaggregation can lead to changes in
      both arteriolar velocity and PCD and may, therefore, impair tissue oxygenation.

PMID- 7525502
TI  - [Locally invasive therapeutic measures in bronchial carcinoma].

PMID- 7525504
TI  - [A decade of fever attacks, weight loss and traveling rheumatoid pain in a 52
      year-old man].

PMID- 7525503
TI  - [Chemotherapy and combined chemoradiotherapy procedures in bronchial carcinoma].

PMID- 7525505
TI  - [33-year-old patient with recurrent severe infections since his childhood].

PMID- 7525507
TI  - Alpha 2-macroglobulin levels in normal human and keratoconus corneas.
AB  - PURPOSE: To compare the levels of alpha 2-macroglobulin, one of the major
      proteinase inhibitors, in corneas with keratoconus to those in normal human
      corneas and corneas with other diseases. METHODS: An immunoperoxidase technique
      was used to visualize the presence of alpha 2-macroglobulin in the corneas.
      Western blot analysis was performed, and the levels of this inhibitor in extracts
      of keratoconus and normal human corneas were subsequently analyzed by a dot blot
      assay. RESULTS: alpha 2-Macroglobulin was demonstrated immunohistochemically in
      the epithelium, stroma, and endothelium of all corneal sections. Compared with
      normal human control specimens, the staining intensity in the epithelium of
      keratoconus corneas was markedly reduced. The majority of scarred and other
      diseased corneas exhibited normal staining intensity for alpha 2-macroglobulin.
      Dot blot assays showed that the alpha 2-macroglobulin levels in the epithelial
      and stromal extracts of keratoconus corneas were lower than those found in normal
      human control counterparts. CONCLUSION: Keratoconus corneas contained a reduced
      level of alpha 2-macroglobulin. This result lends further support to the
      hypothesis that degradation processes may be aberrant in keratoconus.

PMID- 7525508
TI  - Expanded maternal serum alpha fetoprotein screening.

PMID- 7525506
TI  - Mechanisms of retinal and choroidal neovascularization.

PMID- 7525509
TI  - Palliative medicine.

PMID- 7525510
TI  - Presence of hormone-sensitive lipase mRNA in J774 macrophages.

PMID- 7525511
TI  - Nucleolar organizer regions in follicular tumors of the thyroid.
AB  - BACKGROUND: Nucleolar organizer regions (NORs) are loops of ribosomal DNA that
      occur in nucleoli and that transcribe to ribosomal RNA. NORs have been identified
      by means of the Ag-NOR technique in routinely processed tissues, and were found
      to be of discriminative value between some types of benign and malignant lesions.
      METHODS: Follicular lesions of the thyroid (17 adenomas and 25 carcinomas) were
      examined. Ten normal thyroids served as the control group. All slides were
      stained by the Ag-NOR technique and the number of Ag-NOR dots were counted in 50
      randomly selected cells. The mean number of Ag-NORs was calculated for each case.
      Data were statistically analyzed by the Student's unpaired t test. RESULTS: The
      mean Ag-NOR counts were statistically higher in follicular carcinomas as compared
      to either follicular adenomas or the normal thyroid. Higher Ag-NOR counts were
      found in the more aggressively behaving tumors. CONCLUSIONS: It is suggested that
      the Ag-NOR technique could be of use as an adjunct to diagnostic histopathology
      and as an indicator of biologic behavior in follicular tumors of the thyroid.

PMID- 7525512
TI  - Standardization of reagents and methods used in cytological and histological
      practice with emphasis on dyes, stains and chromogenic reagents.
AB  - The need for the standardization of reagents and methods used in the histology
      laboratory is demonstrated. After definitions of dyes, stains, and chromogenic
      reagents, existing standards and standards organizations are discussed. This is
      followed by practical instructions on how to standardize dyes and stains through
      the preparation of reference materials and the development of chromatographic
      methods. An overview is presented of the problems concerned with standardization
      of the Romanowsky-Giemsa stain for cytological and histological application.
      Finally, the problem of how to convince routine dye and stain users of the need
      for standardization in their histology laboratories is discussed.

PMID- 7525513
TI  - The proteoglycan skeleton of the Kurloff body as evidenced by cuprolinic blue
      staining.
AB  - This study deals with the ultrastructure of the chondroitin sulphate
      proteoglycans of the Kurloff body, a large lysosome organelle, metachromatic
      towards Toluidine Blue, of a blood cell unique to the guinea pig and called the
      Kurloff cell. Splenic Kurloff cell from oestrogen-treated guinea pig cells were
      examined after staining with Cuprolinic Blue, a cationic phthalocyanine-like dye,
      in the presence of MgCl2 in a critical electrolyte concentration method. Better
      results were obtained when the fixation-staining by the glutaraldehyde
      Cuprinolinic Blue MgCl2 mixture was preceded by a glutaraldehyde pre-fixation. On
      light microscopy, Kurloff bodies generally exhibited an overall pink and glassy
      metachromasia, sometimes with additional darker metachromatic small dots at their
      peripheries. At the ultrastructural level, the metachromatic central matrix of
      the Kurloff body usually exhibited, as a major feature, a typical network pattern
      of ribbon-like or stellate electron-dense precipitates suggesting the presence of
      a skeleton of Cuprolinic Blue-reactive filamentous structures. Taking into
      account their high anionicity (as shown by the stability of the dye binding in
      the presence of 0.3 M MgCl2) and their susceptibility to chondroitinase ABC,
      these anionic structures were assumed to be related to the proteochondroitin-4
      sulphate previously characterized as the only major sulphated glycoconjugate of
      the Kurloff cell.

PMID- 7525514
TI  - Adult precursor cells in the tail epidermis of Xenopus tadpoles.
AB  - Polyclonal antibodies were raised against Xenopus larva-specific 58 kDa keratin
      (PAK58) and adult-specific 63 kDa keratin (PAK63), in order to examine the origin
      of 63 kDa-keratin-producing cells in the tail skin. By immunofluorescent staining
      of the tail skin, the 58 kDa keratin was recognized in almost all of the larval
      epidermal cells, although a small number of PAK58-negative cells were detected at
      stage 64. In contrast, 63 kDa keratin was immunohistochemically recognized at
      stage 58, but the signal was very weak. The number of epidermal layers in the
      tail epidermis increased during a period from stage 58 to stage 64. At stage 64,
      a small number of PAK63-positive cells was clearly identified in the multilayered
      tail epidermis. Comparative analysis of successive sections showed that PAK63
      positive cells are derived from a cell group differing from PAK58-positive cells.
      Immunohistochemical studies using cultured epidermal cells demonstrated that 58
      kDa keratin is localized in the cytoskeletal bundles of skein cells, whereas 63
      kDa keratin is produced not by skein cells but by basal cells and their
      descendants. These results suggest that basal cells are the adult precursor cells
      within the larval epidermis even in the tail area.

PMID- 7525515
TI  - Adjuvant radiotherapy to sites of previous bulky disease in patients stage IV
      diffuse large cell lymphoma.
AB  - PURPOSE: To evaluate the usefulness of adjuvant radiotherapy to sites of previous
      bulky disease in patients with advanced diffuse large cell lymphoma (DLCL) who
      were in complete remission after chemotherapy. METHODS AND MATERIAL: Two-hundred
      and eighteen patients were initially treated with combined chemotherapy CEOP-bleo
      (cyclophosphamide, epirubicin, vincristine, prednisone, bleomycin) alternating
      with DAC (dexamethasone, cytosine arabinoside, and cisplatinum). One hundred and
      fifty-five patients achieved complete remission. Eighty-eight patients with
      initial bulky disease were randomly assigned to either received (43 patients) or
      not received radiotherapy (45 patients). Dose ranged from 40-50 Gy. RESULTS: The
      median time to treatment failure has not been reached in patients who received
      radiotherapy. At 5 years 72% of the patients treated with the combined therapy
      remain alive disease in free compared to only 35% in the control group. Projected
      survival at 5 years was better in the patients with adjuvant radiotherapy: 81%
      compared to 55% in the patients who received no radiotherapy. Toxicity was mild
      and manageable. No lethal toxicities were observed. CONCLUSION: This treatment
      sequence produced durable control disease in patients with disseminated DLCL and
      bulky disease with acceptable toxicity. The role of radiation therapy in patients
      with disseminated DLCL will be confirmed in large clinical trials, but we felt
      that this sequence of treatment could be useful in patients with this clinical
      condition.

PMID- 7525516
TI  - Extended-field radiotherapy in favorable stage IA-IIA Hodgkin's disease
      (prognostic role of stage).
AB  - PURPOSE: The study was undertaken to evaluate the long-term results in a
      favorable subset of patients with pathological Stage IA-IIA treated with
      irradiation alone. METHODS AND MATERIALS: One hundred and forty-seven adults with
      laparotomy- Staged IA-IIA "favorable" Hodgkin's disease were treated with primary
      subtotal nodal irradiation. Patients with infradiaphragmatic presentation were
      irradiated through paraortic and inguino-iliac node chains (inverted Y field)
      followed by prophylactic mediastinal and supraclavicular fields. RESULTS:
      Actuarial overall survival (OS) at 7 years (median follow-up 77 months) was: 93%
      for the whole series, 94% for Stage I, and 92% for Stage II. The freedom from
      first progression (FFP) (80% for the whole series) showed a statistically
      significant difference (p = 0.008) between Stage I (88%) and Stage II (71%). By
      univariate analysis, stage alone had an independent prognostic significance for
      OS and FFP. Of the 29 relapsed patients, 8 were previously classified as Stage I
      and 21 as Stage II; 16 of 29 (55%) of the relapses occurred in the pelvis and 9
      in extranodal sites. After salvage treatment with chemotherapy all patients
      achieved a second complete remission. Seven second malignancies (two acute
      nonlymphocytic leukemias, one preleukemic syndrome, and four solid tumors) have
      been detected so far. Hypothyroidism was observed in 16% of patients and a
      reversible pulmonary restrictive syndrome in 14% of cases, respectively.
      CONCLUSIONS: Within 7 years from radiation therapy, about one-quarter of the
      patients with Stage II disease will experience a relapse and need intensive
      salvage chemotherapy. This is not invariably successful and safe, for it may be
      complicated by either acute or potentially fatal long-term adverse effects, such
      as second malignancies and cardiac or pulmonary sequelae, in about 5% of
      patients. The high frequency of relapse in Stage IIA patients suggests a combined
      modality approach with relatively short-term chemotherapy not including
      alkylating agents.

PMID- 7525517
TI  - On the mechanism of radiation-induced emesis: the role of serotonin.
AB  - PURPOSE: The aim of this study was to determine the mechanism of action of
      radiation-induced emesis by determining the incidence of radiation-induced emesis
      following hemibody irradiation; the effects of specific antiemetics especially
      ondansetron, a 5-hydroxytryptamine receptor antagonist, and to determine the
      relationship between radiation-induced emesis and serotonin (5-hydroxytryptamine)
      through its active metabolite, 5-hydroxyindoleacetic acid (5-HIAA). METHODS AND
      MATERIALS: Forty-one patients received 53 hemibody treatments of 5-8 Gy following
      intravenous hydration. The patients were divided into three groups according to
      prehemibody irradiation treatment: Group A: no pretreatment antiemetics, 30
      patients; Group B: nonondansetron antiemetics (metoclopramide, dexamethasone,
      prochlorperazine), ten patients; and Group C: ondansetron, 13 patients. The
      incidence of radiation-induced emesis was determined prehemibody irradiation or
      baseline and at 1 h posthemibody irradiation in 38 patients and the results
      expressed as the percent change in 5-HIAA (ng/ug creatinine). RESULTS: The
      incidence of radiation-induced emesis was 82% (14/17) following upper/mid
      hemibody irradiation and 15% (2/11) following lower hemibody irradiation in Group
      A; 50% (3/6) and 25% (1/4) following upper/mid and lower hemibody irradiation
      respectively, in Group B; and 0% (0/13) after upper/mid hemibody irradiation in
      Group C. The incidence of emesis was significantly different (p < 0.001) between
      the patients of Group A and C who received upper/mid hemibody irradiation. The
      percent change in 5-HIAA excretion following upper/mid hemibody irradiation were
      greatest in Group A and smallest in Group C (p < 0.002). The degree of change
      following lower hemibody irradiation (15% incidence of emesis) in Group A was
      lower than upper/mid hemibody irradiation of the same group. CONCLUSION: The
      higher incidence of radiation-induced emesis following upper and mid hemibody
      irradiation in antiemetic naive patients compared to the incidence following
      lower hemibody irradiation suggests that the critical organ responsible for
      radiation sickness is in the abdomen. The control of emesis by ondansetron, a 5
      HT3 receptor antagonist, attests to the efficacy of ondansetron in radiation
      induced emesis and suggests a role for serotonin in mediating radiation-induced
      emesis. Finally, the parallel changes in 5-HIAA and the incidence of emesis
      provides additional evidence for a more direct role for serotonin in radiation
      induced emesis.

PMID- 7525518
TI  - Current status of systemic intravenous radiopharmaceuticals for the treatment of
      painful metastatic bone disease.
AB  - PURPOSE: Intractable bone pain secondary to bone metastasis from prostate, lung,
      breast, and other malignancies is a major problem in the management of the
      oncological patient. Because a number of factors are implicated in the
      pathophysiology of bone pain, a multidisciplinary approach in its assessment and
      treatment is often required. Treatment often includes the use of analgesic drug
      therapy; however, radiation therapy, hormonal therapy, chemotherapy, and surgery
      may also be needed. METHODS AND MATERIALS: The use of systemic radionuclide
      therapy may often be helpful to relieve bone pain and improve the quality of
      life. In the setting of diffuse bone metastasis, intractable to conventional
      therapy, various radioisotopes have been advocated. These include phosphorous-32,
      iodine-131, strontium-89, yttrium-90, samarium-153, and rhenium-186, often as
      either the anionic phosphate or as a ligand (HEDP, EDTMP). RESULTS: When these
      agents are used, pain relief often occurs in approximately 2-4 weeks and lasts
      several weeks to months with responses seen in 60-80% of patients, depending on
      the extent of disease and stage the patient is treated. Retreatment has been
      possible in certain cases with further palliation being offered and improvement
      in the various quality of life parameters being noted. CONCLUSION: Myelotoxicity
      has been a limiting factor with certain isotopes and has led to the development
      of less toxic bone seeking agents. Although these each have unique physical and
      biokinetic properties requiring different doses and protocols for administration,
      they all appear to localize in osteoblastic metastatic sites in sufficient
      amounts to provide bone pain palliation.

PMID- 7525520
TI  - Radiation therapy for esophageal cancer in patients over 80 years old.
AB  - PURPOSE: A retrospective analysis was performed to investigate the treatment
      outcome and the significance of radiation therapy for esophageal cancer in
      patients over 80 years old. METHODS AND MATERIALS: Between 1971 and 1990, 257
      patients with squamous cell carcinoma of the esophagus were treated by radiation
      therapy. Of these, 40 patients over eighty years old were investigated. The
      reasons for radiation therapy were advanced age alone in 22 patients, Stage IV
      disease in 13, and medical problems in 5. Of these, 33 patients (83%) could be
      irradiated over 60 Gy. The cases with Stage I to III disease who received 60 Gy
      or more were defined as the curative radiation therapy group, and the others were
      defined as the palliative radiation therapy group. Actuarial survival rates were
      determined by the Kaplan-Meier method. RESULTS: The 5-year disease-specific
      survival rate for the curative radiation therapy group (n = 25) was 34% with
      three intercurrent deaths. None of the patients in the palliative radiation
      therapy group (n = 15), including 13 cases with Stage IV and two given-up cases,
      survived over 2 years. No severe radiation damage was observed in either group.
      The 5-year disease-specific survival rate was 64% for complete response cases of
      local response, and 8% for partial response and no change cases (p < 0.01). The 5
      year disease-specific survival rate was 64% for the patients with tumors less
      than 5 cm in length, and 8% for the patients with tumors over 5 cm in length (p <
      0.001). No significant survival differences were found in regard to sex and tumor
      location. The patients with superficial spreading type and polypoid type tumors
      according to the radiologic findings had better prognoses than the patients with
      ulcerative type and circumferential type tumors. CONCLUSIONS: Radiation therapy
      is a safe and effective treatment for esophageal cancer in patients over 80 years
      old.

PMID- 7525519
TI  - Radiotherapy in the management of epidemic Kaposi's sarcoma.
AB  - PURPOSE: This study is presented to help define the role of radiotherapy in the
      management of epidemic Kaposi's sarcoma. METHODS AND MATERIALS: Between June 1986
      and June 1993, we treated 453 patients who had acquired immunodeficiency syndrome
      related Kaposi's sarcoma. Two hundred fifty-two patients (55.6%) had received
      previous treatment for their Kaposi's sarcoma: 228 (55.3%) with interferon, and
      116 (25.6%) with Vinblastine. Depending on both tumour size and location,
      patients were treated with extended cutaneous irradiation using 4 MeV electron
      beam energy and/or localized irradiation using 45-100 kV x-ray (cutaneous
      lesions), or 4 MV x-ray (oral tumours). A total of 5015 courses of radiation
      therapy was given. The intention of the treatment was closely linked to the
      anatomic sites. Multiple courses of treatment ranging from 10 to 20 Gy (2.5
      Gy/fraction, 4 times/week) were used for Kaposi's sarcoma involving conjunctiva
      (n = 32 treatments), eyelids (n = 306), lips (n = 170), hands (n = 208), feet (n
      = 417), penis (n = 131), oral mucosa (n = 43), and anal region (n = 5). A second
      group including other cutaneous sites (face, trunk, limbs) was treated with a
      dose of 30 Gy (20 Gy in 2 weeks followed by 2 weeks rest and then a second series
      of 10 Gy in 1 week). RESULTS: For the first group, tolerance was generally good
      excluding oral cavity irradiation, with an effective palliation of symptoms
      (87.8% overall rate of objective responses); an enhanced mucosal reactions was
      noted in patients receiving oropharyngeal irradiation. For the second group, a
      complete regression rate of 85% was observed; tolerance was acceptable:
      complications were severe epidermitis with skin ulceration (5%), exsudative
      epidermitis (26%), dry epidermitis (60%), and varying degrees of erythema (9%).
      There was a significant correlation between risk of recurrence (overall
      recurrence rate of 71% after an average of 7.5 months) and occurrence of
      opportunistic infections: 85% of recurrences appeared concomitantly with
      accelerated course of acquired immunodeficiency syndrome. CONCLUSIONS: We
      conclude that radiotherapy is an efficient treatment for epidemic Kaposi's
      sarcoma (EKS): doses of 15.2 Gy for oral lesions and 20 Gy for lesions involving
      conjunctiva, eyelids, lips, hands, feet, penis, and anal region were sufficient
      to produce shrinkage of the tumour and good palliation of symptoms. For the other
      cutaneous sites, 30 Gy local field irradiation could be safely given with better
      short-term response. Prophylactic measures with antifungal treatment should be
      systematically associated with oropharyngeal irradiation, to improve tolerance to
      the treatment.

PMID- 7525521
TI  - Urinary alpha-amylase and serum macroamylase activities in dogs with proteinuria.
AB  - Activities of urinary alpha-amylase and serum macroamylase; concentrations of
      serum creatinine, immunocomplexes, and urinary protein; and patterns of
      proteinuria were determined in 35 dogs with proteinuria. Urinary alpha-amylase
      activity ranged from 37 to 4,031 U/L. Macroamylasemia was detected in 77.14% of
      dogs and the percentage of alpha-amylase precipitated ranged from 4.68 to 61.63.
      Serum alpha-amylase activity after immunoglobulin precipitation ranged from 654
      to 6,390 U/L in 51.42% of the dogs; the values were higher than the reference
      limits. Concentrations of serum creatinine and immunocomplexes were higher than
      reference limits for 25.71 and 60% of dogs, respectively. Urinary protein
      concentrations ranged from 0.1 to 8.9 g/L. All the patterns of proteinuria were
      represented. Linear regression indicated correlations between urinary alpha
      amylase activities, serum creatinine concentrations (P < 0.01), and concentration
      of immunocomplexes (P < 0.05). Mann-Whitney test indicated significantly higher
      urinary alpha-amylase activity (P < 0.01) and percentage of alpha-amylase
      precipitated (P < 0.05) in dogs with renal insufficiency.

PMID- 7525523
TI  - Association of vascular endothelial growth factor expression with tumor
      angiogenesis and with early relapse in primary breast cancer.
AB  - Angiogenesis is an independent prognostic indicator in breast cancer. In this
      report, the relationship between expression of vascular endothelial growth factor
      (VEGF; a selective mitogen for endothelial cells) and the microvessel density was
      examined in 103 primary breast cancers. The expression of VEGF was evaluated by
      immunocytochemical staining using anti-VEGF antibody. The microvessel density,
      which was determined by immunostaining for factor VIII antigen, in VEGF-rich
      tumors was clearly higher than that in VEGF-poor tumors (P < 0.01). There was a
      good correlation between VEGF expression and the increment of microvessel
      density. Furthermore, postoperative survey demonstrated that the relapse-free
      survival rate of VEGF-rich tumors was significantly worse than that of VEGF-poor
      tumors. It was suggested that the expression of VEGF is closely associated with
      the promotion of angiogenesis and with early relapse in primary breast cancer.

PMID- 7525522
TI  - Mitotic activation of c-Src is suppressed by Csk.
AB  - The kinase activity of the proto-oncogene product, c-Src, increases during
      mitosis through partial dephosphorylation of Tyr527, the negative regulatory site
      of c-Src. To examine whether or not Csk, a candidate kinase specific for Tyr527,
      is involved in this regulation, we developed a Balb/c 3T3 cell line
      overexpressing Csk and a Csk-deficient cell line. The overexpression of wild-type
      Csk caused significant suppression of the c-Src activity during mitosis. A
      membrane-targeted Csk, which has an amino-terminal myristylation signal of c-Src,
      exhibited an effective suppression of the c-Src activity, even though its
      expression level was lower than that of endogenous Csk. Concomitant with the
      suppression of the c-Src activation, the level of tyrosine phosphorylation of a
      cortactin-related protein, a potential substrate of c-Src in vivo, was reduced.
      In contrast, the Csk-deficient cells exhibited constitutive activation of c-Src,
      which showed no significant change in its activity during mitosis. These results
      suggest that Csk indeed participates in the regulation of the c-Src activity
      during mitosis.

PMID- 7525524
TI  - Virus isolate-specific antibodies against hypervariable region 1 of the hepatitis
      C virus second envelope protein, gp70.
AB  - Hypervariable region 1 (HVR1), located in the N-terminal region of a putative
      second envelope glycoprotein (gp70) of hepatitis C virus (HCV), contains
      immunological B-cell epitopes which might be neutralizing epitopes. To clarify
      whether B-cell epitopes within HVR1 are common among virus isolates or specific
      for the homologous virus isolate, we examined the reactivities of sera from 53
      patients with chronic hepatitis or hepatocellular carcinoma/liver cirrhosis
      against two different HVR1 peptides (HVR1 I-1 and HVR1 Y-1) derived from patient
      I with sporadic acute hepatitis and an asymptomatic carrier Y, respectively,
      using our original assay system for the detection of anti-HVR1 antibody. All
      patients examined had a history of blood transfusion. Most sera showed no
      reactivity with either HVR1 I-1 or HVR1 Y-1 peptide. Only seven and fourteen
      serum samples reacted significantly, although weakly, with HVR1 I-1 and HVR1 Y-1
      peptides, respectively, compared with the serum from patient I or asymptomatic
      carrier Y. The blood transfusions of most reactive cases had occurred more than
      thirty years earlier. Six cases reacted with both HVR1 I-1 and HVR1 Y-1 peptides,
      but further analysis revealed that only three cases reacted weakly with the
      peptide for either epitope I or II, identified within HVR1 I-1. These results
      indicate that the B-cell epitopes within HVR1 are fairly specific for the
      homologous virus isolate, and this may represent a serious difficulty in the
      development of a vaccine against HCV.

PMID- 7525526
TI  - Responses of lung parenchyma and airways to tachykinin peptides in piglets.
AB  - The tachykinin peptides substance P (SP) and neurokinin A (NKA) have been shown
      to induce tracheal smooth muscle contraction in piglets, and the enzyme neutral
      endopeptidase has been shown to modulate this effect. In these studies, we
      compared the SP and NKA responsiveness of piglet airways and lung parenchymal
      tissues in anesthetized paralyzed open-chest piglets 2-3 wk old, partitioning
      total lung resistance (RL) into airway resistance (Raw) and tissue resistance
      (Rti). During tidal breathing, pressure was measured at the trachea and in two
      alveolar regions by means of alveolar capsules. Intravenous administration of SP
      caused concentration-dependent increases in Rti and Raw and a decrease in dynamic
      lung compliance. Under baseline conditions, Rti contributed 74.6 +/- 1.9% (SE) of
      RL, and at any level of constriction, Rti accounted for > 50% of RL. The
      responses of Rti and Raw to NKA were negligible and were always significantly
      weaker than those to SP. These results indicate that both central airways and
      tissue contractile elements respond vigorously to SP, but not to NKA, in maturing
      piglets.

PMID- 7525525
TI  - The formation of human synovial joint cavities: a possible role for hyaluronan
      and CD44 in altered interzone cohesion.
AB  - During fetal development, cavitation occurs within the primitive skeleton along
      planes destined to become the articular surfaces of synovial joints. A
      histochemical study of human fetal limbs was undertaken to identify the cell
      types involved in this cavitation and the possible role of interactions between
      cells and extracellular matrix. Cryostat sections were stained with antibodies to
      CD68, factor VIII related antigen, prolyl hydroxylase, beta 1 integrin, VCAM-1,
      proliferating cell nuclear antigen, chondroitin-4 sulphate, chondroitin-6
      sulphate, hyaluronan synthase and CD44. Similar sections were reacted for uridine
      diphosphoglucose dehydrogenase (UDPGD) and acid phosphatase activity. Hyaluronan
      was demonstrated using an aggrecan core protein hyaluronan binding region probe.
      Macrophages were present prior to cavitation in the periphery of joint interzones
      but not at the presumptive joint line in the central interzone. Fibroblastic
      cells were present throughout. Absence of local VCAM-1 expression indicated that
      cavitation was temporally distinct from full fibroblast-like synoviocyte
      differentiation. CD44 was expressed by interzone cells at all stages. Staining
      for hyaluronan and hyaluronan synthase, but not chondroitin sulphates was present
      in the interzone before and at the time of cavitation. UDPGD activity was
      increased in a narrow band of cells at the presumptive joint line prior to
      cavitation. These findings suggest that joint cavitation is dependent on the
      behaviour of fibroblastic cells and/or adjacent chondrocytes, rather than
      macrophages. Since UDPGD activity is involved in hyaluronan synthesis, it is
      proposed that joint cavitation is facilitated by a rise in local hyaluronan
      concentration in an area of tissue where cohesion is dependent on the interaction
      between cellular CD44 and extracellular hyaluronan. As proposed by Toole et al.
      (1984) such a local rise in hyaluronan concentration may lead to a switch from
      intercellular cohesion to dissociation, leading to tissue cavitation.

PMID- 7525527
TI  - Role of EDRF in the regulation of regional blood flow and vascular resistance at
      rest and during exercise in conscious dogs.
AB  - The contribution of endothelium-derived relaxing factor (EDRF) to the regulation
      of regional vascular resistance and tissue blood flow at rest and during acute
      moderate exercise was studied in chronically instrumented conscious dogs.
      Radioactive microspheres were injected before and during exercise to measure
      regional blood flow. An infusion of nitro-L-arginine (L-NA), an analogue of L
      arginine, was used to inhibit the synthesis of EDRF and resulted in a significant
      increase in mean arterial pressure, associated with significantly elevated
      vascular resistance in heart, skeletal muscle, renal and splanchnic circulations
      and with decreases in tissue blood flow in those regions at rest. Acute exercise
      caused a typical redistribution of blood flow, in which there was vasodilation in
      heart and working skeletal muscles, accompanied by vasoconstriction in kidney and
      splanchnic circulations. L-NA resulted in significantly elevated vascular
      resistance during vasodilation in heart and working skeletal muscles and also
      significantly increased vasoconstriction in renal cortex, stomach, pancreas,
      liver, and colon during exercise. Blood flows during exercise were largely
      unaffected by L-NA treatment. Our results suggest that whereas EDRF functions to
      regulate basal vascular tone and vascular resistance during exercise, EDRF has a
      minor role in determining the pattern of the redistribution of tissue blood flow
      during exercise.

PMID- 7525528
TI  - Biexponential pulmonary clearance of 99mTc-DTPA induced by detergent aerosol.
AB  - We measured the pulmonary clearance of technetium-99m-labeled diethylenetriamine
      pentaacetatic acid (99mTc-DTPA) for 3 h after perturbation of the surfactant
      system by administration of the detergent dioctyl sodium sulfosuccinate in
      aerosol. Forty-two rabbits were anesthetized with pentobarbital sodium.
      Tracheostomies were performed, and the rabbits were mechanically ventilated.
      Increasing concentrations of detergent (0.125-2%) or vehicle were given for 5
      min, and clearance measurements were performed immediately or 60 min after
      detergent administration. No animals developed respiratory distress. After
      vehicle, the clearance was monoexponential with a half-life of 153 min. Detergent
      induced a biexponential clearance with a rapidly clearing additional pool of
      radioactivity with a half-life of 5-15 min. The relative amount of radioactivity
      clearing rapidly increased with detergent concentration. The detergent effect was
      partly reversible. We conclude that detergent induces a biexponential clearance
      of 99mTc-DTPA by accelerating the transfer of tracer across the alveolocapillary
      barrier in a proportion of lung units in a dose-related manner.

PMID- 7525529
TI  - Inhibition of neutrophil and eosinophil adhesion to venules of rat trachea by
      beta 2-adrenergic agonist formoterol.
AB  - Many inflammatory mediators trigger the adhesion of leukocytes to the vascular
      endothelium. We sought to determine whether the beta 2-adrenergic receptor
      agonist formoterol can inhibit the adhesion of neutrophils and eosinophils to the
      endothelium of venules in the rat airway mucosa. We also tested whether this
      action is mediated by beta 2-adrenergic receptors. Inflammation was induced in
      the airways of anesthetized pathogen-free F344 rats by injecting substance P (5
      micrograms/kg) or bradykinin (10 mg/kg) intravenously. The rats were perfused
      with fixative 5 min later, and the tracheas were removed. Adherent intravascular
      neutrophils and eosinophils, stained by a histochemical reaction for
      myeloperoxidase, were counted in tracheal whole mounts. We found that, after the
      injection of substance P, formoterol (0.1, 1.0, or 10.0 micrograms/kg i.v.)
      reduced the number of adherent neutrophils by 8, 59, or 56% and reduced the
      number of eosinophils by 59, 90, or 86%, respectively. The three doses of
      formoterol reduced the amount of substance P-induced extravasation of Monastral
      blue by 21, 66, or 80%, respectively. Both effects of formoterol were blocked by
      the beta 2-adrenergic receptor antagonist ICI-118,551, which by itself produced
      neither leukocyte adhesion nor plasma extravasation. After the injection of
      bradykinin, the three doses of formoterol reduced the number of adherent
      neutrophils by 28, 67, or 62% and reduced the number of eosinophils by 17, 38, or
      57%, respectively. We conclude that formoterol, acting via beta 2-adrenergic
      receptors, not only can reduce the amount of plasma leakage but also can reduce
      the number of neutrophils and eosinophils that adhere to the vascular endothelium
      at sites of inflammation.

PMID- 7525532
TI  - Fundamentals of bone marrow examination.
AB  - Bone marrow evaluation is an important and effective way of diagnosing and
      evaluating primary hematologic and metastatic neoplasms as well as nonhematologic
      disorders. Many variations exist for obtaining marrow samples (sites,
      instruments, techniques); however, the method outlined in this article has proven
      reliable. Complete evaluation of bone marrow samples should include a brief
      patient history, pertinent laboratory data, peripheral blood films, bone marrow
      aspirate smears and sections, and biopsy imprints and sections. Routine
      examination of the bone marrow as described previously is usually adequate for
      interpretation. However, application of additional studies using cytochemical,
      immunocytochemical, immunohistochemical, cytogenetic, and molecular techniques
      may prove to be of critical importance in the diagnosis of hematologic
      malignancies.

PMID- 7525531
TI  - Blood smear examination.
AB  - Despite recent advances in the automation of clinical hematology laboratories, a
      careful microscopic examination of an appropriately prepared and stained blood
      smear continues to maintain its status as the most informative and useful
      diagnostic procedure, and offers a simple, reliable means of verifying results
      generated by automated analyzers. A systematic approach to a comprehensive
      evaluation of blood cells and related findings is described.

PMID- 7525530
TI  - Cardiovascular effects of NG-methyl-L-arginine in chronically instrumented
      conscious dogs.
AB  - The cardiovascular effects of nitric oxide blockade were examined in five
      conscious chronically instrumented dogs. The hypothesis tested was that nitric
      oxide release plays a role in vascular tone and regional organ blood flow under
      physiological conditions. Aortic pressures; the first derivative of the left
      ventricular pressure; cardiac output (CO); heart rate; and carotid, coronary,
      renal, hepatic, and portal blood flows were recorded before and after bolus
      injection of 5, 10, and 20 mg/kg of NG-methyl-L-arginine (L-NMA). In response to
      L-NMA, mean arterial pressure increased by 7, 20, and 35%, respectively, in a
      dose-dependent manner, whereas CO decreased. CO reduction was sustained at the
      highest dose, whereas peripheral blood flows were not altered. These data suggest
      that blocking basal nitric oxide synthesis by administering L-NMA leads to a
      modest dose-dependent pressor response despite a marked and sustained reduction
      in CO recorded at the highest dose of L-NMA. Moreover, within our dose range,
      although the nitric oxide synthase inhibition provides a significant pressor
      response, it does not alter the resting carotid, coronary, renal, hepatic, and
      portal blood flows.

PMID- 7525534
TI  - Genetic mechanisms in childhood psychiatric disorders.
AB  - OBJECTIVE: This review summarizes research findings on the genetics of several
      childhood psychiatric disorders. METHOD: One hundred fifty papers were reviewed
      from the past several decades and were selected because they have suggested that
      genetic factors may play a role in the etiology of certain childhood disorders.
      This review is not meant to be exhaustive but rather has emphasized those
      disorders for which a genetic etiology has been proposed by different research
      groups. RESULTS: The more classical approaches to genetic research are reviewed
      and critiqued. The status of research for a number of childhood disorders is
      summarized. The molecular basis for several developmental disorders is presented
      and the prospects for arriving at a similar molecular understanding for other
      childhood psychiatric illnesses are discussed. CONCLUSIONS: Genetic factors play
      a determining role for certain developmental disorders. However, the molecular
      basis for other psychiatric disorders has yet to be elucidated and there are
      complicating factors that bear on genetic research of complex behavioral
      disorders.

PMID- 7525533
TI  - Ratings of hyperactivity and developmental indices: should clinicians correct for
      developmental level?
AB  - This study assessed the relationship between parent and teacher ratings of
      hyperactivity and developmental indices (chronological age, IQ, and mental age)
      in two groups of children. Subjects were drawn separately from two psychiatric
      clinics: (a) a general clinical sample, largely of normal ability, seen for a
      multitude of psychiatric and behavioral problems, and (b) a developmental clinic
      sample, comprising children with cognitive delays and seen for ADHD or the
      absence of ADHD. The results showed consistent negative correlations between
      chronological age and severity of hyperactivity symptoms; however, these occurred
      mainly within the developmental clinic sample. Only 4 of 27 comparisons (15%)
      between mental age and hyperactivity ratings (all confined to the developmentally
      delayed sample) showed a significant correlation. When chronological age was
      first partialled out, the correlations between ratings of hyperactivity and
      mental age ceased to be significant. Findings suggest that chronological age
      should be taken into consideration when behavior ratings are used to assess
      cognitively delayed children for ADHD. However, the results do not support
      guidelines stating that mental age must be used to determine which norms should
      be applied when such children are evaluated clinically.

PMID- 7525535
TI  - Molecular analysis of RNAI control of repB translation in IncB plasmids.
AB  - The translation of RepA, the replication initiation protein of the IncB plasmid
      pMU720, requires that its mRNA (RNAII) folds to form a pseudoknot immediately
      upstream of the repA Shine-Dalgarno sequence. The formation of this pseudoknot is
      dependent in turn on the translation and correct termination of a leader peptide,
      RepB. A small countertranscript RNA, RNAI, controls the replication of pMU720 by
      interacting with RNAII to negatively regulate the expression of repA both
      directly, by sequestering the proximal bases required for pseudoknot formation,
      and indirectly, by inhibiting the translation of repB. Inhibition of the
      translation of repB by RNAI was found to depend on the close proximity of the
      RNAI-RNAII complex to the translational initiation region of repB, indicating
      that the primary mechanism of RNAI control involves steric hindrance. Disruption
      of RNAI control of repB had only a small effect on the copy number of the IncB
      plasmid, indicating that inhibition of the expression of repA by RNAI is achieved
      predominantly by inhibition of pseudoknot formation rather than by inhibition of
      repB translation.

PMID- 7525536
TI  - Structural studies of the side chain of outer membrane lipopolysaccharide from
      Pseudomonas syringae pv. coriandricola W-43.
AB  - The lipopolysaccharide (LPS) was isolated from Pseudomonas syringae pv.
      coriandricola W-43 by hot phenol-water extraction. Rhamnose and 3-N-acetyl-3
      deoxyfucose were found to be the major sugar constituents of the LPS together
      with N-acetylglucosamine, N-acetylgalactosamine, heptose, and 3-deoxy-D-manno
      octulosonic acid (Kdo). The main fatty acids of lipid A of the LPS were 3-OH
      C:10, C12:0, 2-OH-C12:0, and 3-OH-C12:0. The O-specific polysaccharide liberated
      from the LPS by mild-acid hydrolysis was purified by gel permeation
      chromatography. The compositional analysis of the O-specific polysaccharide
      revealed the presence of L-rhamnose and 3-N-acetyl-3-deoxy-D-fucose in a molar
      ratio of 4:1. The primary structure of the O-specific polysaccharide was
      established by methylation analysis together with 1H and 13C nuclear magnetic
      resonance spectroscopy, including two-dimensional shift-correlated and one
      dimensional nuclear Overhauser effect spectroscopy. The polysaccharide moiety was
      found to consist of a tetrasaccharide rhamnan backbone, and 3-N-acetyl-3-deoxy-D
      fucose constitutes the side chain of the branched pentasaccharide repeating unit
      of the polysaccharide.

PMID- 7525537
TI  - Role of the rfe gene in the biosynthesis of the Escherichia coli O7-specific
      lipopolysaccharide and other O-specific polysaccharides containing N
      acetylglucosamine.
AB  - We report that rfe mutants of wild-type strains of Escherichia coli O7, O18, O75,
      and O111 did not express O-specific polysaccharide unless the rfe mutation was
      complemented by a cloned rfe gene supplied in a plasmid. The O polysaccharides in
      these strains are known to have N-acetylglucosamine (GlcNAc) in their O repeats.
      In addition, in vitro transferase assays with bacterial membranes from either the
      O7 wild-type strain or its isogenic rfe mutant showed that GlcNAc is the first
      carbohydrate added onto the lipid acceptor in the assembly of the O7 repeat and
      that this function is inhibited by tunicamycin. Our results indicate that the rfe
      gene product is a general requirement for the synthesis of O polysaccharides
      containing GlcNAc.

PMID- 7525538
TI  - Monoclonal antibodies that distinguish inner core, outer core, and lipid A
      regions of Pseudomonas aeruginosa lipopolysaccharide.
AB  - In order to examine the immunochemistry of the core-lipid A region of Pseudomonas
      aeruginosa lipopolysaccharide (LPS), monoclonal antibodies (MAbs) specific for
      this region were produced in mice. Immunogen was prepared by coating a rough
      mutant of P. aeruginosa with column-purified core oligosaccharide fractions in
      order to enhance the immune response to the LPS core-lipid A region. Fourteen
      hybridoma clones were isolated, characterized, and further divided into three
      groups on the basis of their reactivities to rough LPS antigens in both enzyme
      linked immunosorbent assays and Western immunoblots. In addition, another MAb, 18
      19, designated group 1, was included in this study for defining core-lipid A
      epitopes. MAb 18-19 recognizes the LPS core-plus-one O-repeat unit of the
      serologically cross-reactive P. aeruginosa O2, O5, and O16. Group 2 MAbs are
      specific for the LPS outer core region and reacted with P. aeruginosa O2, O5, O7,
      O8, O10, O16, O18, O19, and O20, suggesting that these serotypes share a common
      outer core type. Group 3 MAbs recognize the inner core region and reacted with
      all 20 P. aeruginosa serotypes as well as with other Pseudomonas species,
      revealing the conserved nature of this region. Group 4 MAbs are specific for
      lipid A and reacted with all gram-negative organisms tested. Immunoassays using
      these MAbs and well-defined rough mutants, in addition to the recently determined
      P. aeruginosa core structures, have allowed us to precisely define immunodominant
      epitopes within the LPS core region.

PMID- 7525539
TI  - Concentrations of 4.5S RNA and Ffh protein in Escherichia coli: the stability of
      Ffh protein is dependent on the concentration of 4.5S RNA.
AB  - We measured the concentrations of both 4.5S RNA and Ffh protein under a variety
      of growth conditions and found that there were 400 molecules of 4.5S RNA per
      10,000 ribosomes in wild-type cells and that the concentration of Ffh protein was
      one-fourth of that. This difference in concentration is 1 order of magnitude less
      than that previously reported but still significant. Pulse-chase labeling
      experiments indicated that Ffh protein is unstable in cells carrying ffh on high
      copy-number plasmids and that simultaneous overproduction of 4.5S RNA stabilizes
      Ffh protein. Our analyses show that free Ffh protein is degraded with a half-life
      of approximately 20 min. We also tested whether three previously isolated
      suppressors of 4.5S RNA deficiency could reduce the requirement for Ffh protein.
      Since the two sffE suppressors do not suppress the Ffh requirement, we suggest
      that 4.5S RNA either acts in a sequential reaction with Ffh or has two functions.

PMID- 7525541
TI  - Predictors of clozapine response in schizophrenia.
AB  - The introduction of the atypical neuroleptic, clozapine, has had widespread
      influence not only on the treatment of the seriously mentally ill patient, but
      also on new drug development and on hypotheses of the pathophysiology of
      schizophrenia. While clozapine differs from traditional neuroleptics in its lack
      of extrapyramidal side effects (EPS), it also is distinct in its profile of
      neurotransmitter receptor affinities. In our work examining the clinical and
      biological effects of clozapine in patients with schizophrenia, we have
      identified the presence of EPS during typical neuroleptic treatment as a
      consistent predictor of subsequent good response to clozapine. Further, our data
      suggest that clozapine should not be reserved for the most chronically ill
      patients, but rather be utilized in patients with less chronic courses of
      schizophrenia. Biological predictors of clozapine response are consistent with
      dopaminergic, serotonergic, and noradrenergic facets to its mechanism of action.

PMID- 7525540
TI  - Comparative analysis of the replicon regions of eleven ColE2-related plasmids.
AB  - The incA gene product of ColE2-P9 and ColE3-CA38 plasmids is an antisense RNA
      that regulates the production of the plasmid-coded Rep protein essential for
      replication. The Rep protein specifically binds to the origin and synthesizes a
      unique primer RNA at the origin. The IncB incompatibility is due to competition
      for the Rep protein among the origins of the same binding specificity. We
      localized the regions sufficient for autonomous replication of 15 ColE plasmids
      related to ColE2-P9 and ColE3-CA38 (ColE2-related plasmids), analyzed their
      incompatibility properties, and determined the nucleotide sequences of the
      replicon regions of 9 representative plasmids. The results suggest that all of
      these plasmids share common mechanisms for initiation of DNA replication and its
      control. Five IncA specificity types, 4 IncB specificity types, and 9 of the 20
      possible combinations of the IncA and IncB types were found. The specificity of
      interaction of the Rep proteins and the origins might be determined by insertion
      or deletion of single nucleotides and substitution of several nucleotides at
      specific sites in the origins and by apparently corresponding insertion or
      deletion and substitution of amino acid sequences at specific regions in the C
      terminal portions of the Rep proteins. For plasmids of four IncA specificity
      types, the nine-nucleotide sequences at the loop regions of the stem-loop
      structures of antisense RNAs are identical, suggesting an evolutionary
      significance of the sequence. The mosaic structures of the replicon regions with
      homologous and nonhomologous segments suggest that some of them were generated by
      exchanging functional parts through homologous recombination.

PMID- 7525542
TI  - G-CSF and the management of clozapine-induced agranulocytosis.
AB  - The agranulocytosis associated with clozapine is, indeed, a serious medical
      disorder. Patients experience prolonged and profound severe granulocytopenia-
      often with absolute neutrophil counts of less than 100/cu mm. Patients suffer
      neutropenic sepsis and often are as sick as patients undergoing induction
      chemotherapy for lymphoma or leukemia. Thus, it is important to evaluate the
      state-of-the-art management of such patients and to define the role of growth
      factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF). Early use of G-CSF or GM-CSF can
      shorten the duration of granulocytopenia from a mean of 16 to 8 days and reduce
      the morbidity of the disorder. Such intervention can potentially decrease the
      total cost of agranulocytosis. Further issues under consideration are the early
      use of hematopoietic growth factors prior to the onset of agranulocytosis and the
      use of these factors for the outpatient management of this disorder.

PMID- 7525543
TI  - The effects of clozapine on neurocognition: an overview.
AB  - Clozapine has proved effective in alleviating a wide range of psychiatric
      symptoms in schizophrenia. Its effects on cognitive function in schizophrenia are
      more variable. Clozapine appears to have a salutary effect on some aspects of
      attention, response speed, and fluency, whereas it appears to have a mild but
      adverse effect on visual memory and some executive functions. This profile may be
      related to the affinity of clozapine for dopaminergic type I and muscarinic
      receptors and relative lack of affinity for dopaminergic type II receptors.

PMID- 7525544
TI  - Modification of recombinant human granulocyte colony-stimulating factor (rhG-CSF)
      and its derivative ND 28 with polyethylene glycol.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been
      obtained from genetically engineered Escherichia coli as an unglycosylated
      protein. Both native glycosylated hG-CSF and rhG-CSF are rapidly cleared from the
      circulation, which may limit their effectiveness for clinical use. To improve
      this biological property, rhG-CSF and its derivative ND 28, which has a higher
      specific activity than does rhG-CSF, were modified with polyethylene glycol
      (PEG). Modified rhG-CSF and ND 28 in which 1 to 3 mol of PEG were bound, were
      purified by two-step chromatography and characterized by several methods. The
      results of their physicochemical characterization suggest that PEG-modification
      does not appreciably change the conformation of rhG-CSF and ND 28. As a result of
      the whole characterization, the PEG-modification of rhG-CSF and ND 28 enhanced
      the stability of rhG-CSF and ND 28 and decreased the plasma clearance rate, which
      led to more effective hemopoiesis.

PMID- 7525545
TI  - Polyamino acids that inhibit the interaction of yeast translational elongation
      factor-3 (EF-3) with ribosomes.
AB  - EF-3 is a translational elongation factor specific to yeasts and fungi. Its
      carboxy-terminal region contains three lysine-clusters and is very basic. The
      region has been reported to be responsible for the interaction with ribosomes
      [Ishiyama, A., Ogawa, K., & Miyazaki, M. (1992) in Abstracts of the 15th Annual
      Meeting of the Molecular Biology Society of Japan, p.190]. To find specific
      inhibitors for the interaction of EF-3 with ribosomes, the effects of two basic
      polyamino acids, poly-L-(Lys) and poly-L-(Arg), and two acidic polyamino acids,
      poly-L-(Asp) and poly-L-(Glu), were examined using two assay systems for ATPase
      of EF-3. One was for the ribosome-activated ATPase and the other for the
      intrinsic (ribosome-independent) ATPase of EF-3. Basic polyamino acids were
      expected to act as analogues of the carboxy-terminal region of EF-3, and acidic
      ones to interact with EF-3. The basic polyamino acids inhibited the ribosome
      activated ATPase, but they also inhibited the intrinsic one more effectively.
      Acidic polyamino acids, poly-L-(Asp) and poly-L-(Glu), inhibited the ribosome
      activated ATPase but not the intrinsic one. Thus, acidic polyamino acids could be
      specific inhibitors of the interaction between EF-3 and ribosomes. Furthermore, a
      system for detecting the binding of EF-3 to ribosomes was constructed. That is,
      ribosome-bound EF-3 was detected by measuring the ATPase on precipitated
      ribosomes after a mixture of EF-3 and ribosomes had been ultracentrifuged. Using
      this system, poly-L-(Asp) was shown to inhibit the binding of EF-3 to ribosomes
      directly.

PMID- 7525549
TI  - Adenylate cyclase toxin (CyaA) of Bordetella pertussis. Evidence for the
      formation of small ion-permeable channels and comparison with HlyA of Escherichia
      coli.
AB  - The interaction between the adenylate cyclase toxin (CyaA) of Bordetella
      pertussis and lipid was studied using the lipid bilayer assay. The addition of
      CyaA to the aqueous phase bathing lipid bilayer membranes composed of different
      lipids resulted in the increase of the membrane conductance. This increase was
      rather small for membranes formed of pure lipids as compared with lipid mixtures
      such as asolectin. The toxin formed in asolectin membranes small transient ion
      permeable channels with a single-channel conductance of 27 pS in 1 M KCl, which
      is considerably smaller than that of the alpha-hemolysin (HlyA) of Escherichia
      coli (1500 pS). Experiments with different salts suggested that the CyaA-induced
      channels were exclusively cation-selective because of negative charges localized
      at the channel mouth. The single-channel conductance of channels initiated by
      CyaA was independent of whether the toxin was purified from B. pertussis or from
      recombinant E. coli. However, the channel-forming activity of the CyaA expressed
      in B. pertussis was substantially higher than that of the recombinant toxin.
      Experiments with mutant forms of CyaA suggested that both the activation of CyaA
      by CyaC and the hemeolytic part of the toxin, but not the repeats and the cyclase
      activity, are required for channel formation in lipid bilayer membranes.

PMID- 7525547
TI  - Localization of the insulin receptor binding sites for the SH2 domain proteins
      p85, Syp, and GAP.
AB  - The insulin receptor is known to interact with the SH2 domain proteins p85 (the
      regulatory subunit of phosphatidylinositol 3-kinase), Syp (a tyrosine
      phosphatase), and GAP (GTPase-activating protein). In this study, we mapped the
      insulin receptor binding sites for each of these proteins by examining the
      ability of phosphopeptides, corresponding to insulin receptor phosphorylation
      sites, and mutant insulin receptors to inhibit an insulin receptor-SH2 domain
      interaction. Precipitation of partially purified insulin receptors by glutathione
      S-transferase fusion proteins containing the N-terminal SH2 domains of p85 and
      GAP and both SH2 domains of Syp was demonstrated. The effect of the addition of
      each phosphopeptide on insulin receptor precipitation was tested. pY1322, the C
      terminal insulin receptor peptide, inhibited insulin receptor precipitation by
      both p85- and Syp-GST. The NPXY internalization domain peptide inhibited insulin
      receptor precipitation by GAP-GST. These data were confirmed by mutant insulin
      receptor experiments. The insulin receptor C-terminal mutants, delta CT and Y/F2,
      were not precipitated by p85- or Syp-GST and the NPXY mutant insulin receptors,
      delta Ex16 and HI delta NPEY, were not precipitated by GAP-GST. Therefore, we
      conclude that p85 and Syp bind to the insulin receptor C terminus at tyrosine
      1322 and GAP binds to the insulin receptor NPXY domain at tyrosine 960.

PMID- 7525548
TI  - Integrin alpha 4 beta 1-mediated melanoma cell adhesion and migration on vascular
      cell adhesion molecule-1 (VCAM-1) and the alternatively spliced IIICS region of
      fibronectin.
AB  - The integrin receptor alpha 4 beta 1 (also known as VLA-4) binds two different
      ligands, the endothelial cell surface protein vascular cell adhesion molecule-1
      (VCAM-1) and the extracellular matrix component fibronectin. Three distinct sites
      in fibronectin are recognized by alpha 4 beta 1. Two of these (represented by
      peptides CS1 and CS5) are present in the alternatively spliced IIICS region and
      lie in separate, independently spliced segments of this region. A third site
      resides in the adjacent constitutively expressed HepII domain. Recombinant
      proteins containing the HepII domain and different splice variants of the IIICS
      have been generated and compared for their ability to mediate cell attachment,
      spreading and migration. The activity of these proteins has also been compared
      with that of a recombinant soluble form of VCAM-1 (rsVCAM-1). All the recombinant
      proteins supported A375-SM human melanoma cell attachment and spreading in an
      alpha 4 beta 1-dependent manner, but had varied adhesive activities with rsVCAM-1
      > fibronectin variants containing the CS1 sequence >> other fibronectin variants.
      Low concentrations of rsVCAM-1 and CS1-containing fibronectin variants
      effectively supported cell migration in a trans-filter assay; however, cell
      motility was retarded at high concentrations of the same proteins. Fibronectin
      variants lacking CS1 supported little or no migration. To obtain further insight
      into the molecular basis of this varied adhesive activity, apparent dissociation
      constants for each of the recombinant proteins were measured using a solid phase
      receptor-ligand binding assay. The results revealed a hierarchy of ligand
      affinities that mirrored their adhesive activity (rsVCAM-1 > fibronectin variants
      containing CS1 >> other fibronectin variants).

PMID- 7525550
TI  - Identification of tyrosine 620 as the major phosphorylation site of myelin
      associated glycoprotein and its implication in interacting with signaling
      molecules.
AB  - Myelin-associated glycoprotein (MAG) is a myelin-specific cell adhesion molecule
      of the immunoglobulin supergene family and is tyrosine-phosphorylated in the
      developing brain. To define the role of MAG in signal transduction, the tyrosine
      phosphorylation sites were analyzed. The major tyrosine phosphorylation residue
      was identified as Tyr-620, which was found to interact specifically with the SH2
      domains of phospholipase C (PLC gamma). This domain may represent a novel protein
      binding motif that can be regulated by tyrosine phosphorylation. MAG also
      specifically bound the Fyn tyrosine kinase, suggesting that MAG serves as a
      docking protein that allows the interaction between different signaling
      molecules.

PMID- 7525546
TI  - Lysosomal enzyme replacement using alpha 2-macroglobulin as a transport vehicle.
AB  - Improvement of the delivery of exogenous enzymes is essential to achieve
      effective enzyme replacement therapy in lysosomal storage diseases. To test
      whether alpha 2-macroglobulin, an endogenous plasma protein, could serve as a
      transport vehicle of therapeutic agents to cells, alpha 2-macroglobulin and acid
      alpha-glucosidase or alpha-galactosidase A were coupled using two
      heterobifunctional cross-linking reagents. The alpha-glucosidase-alpha 2
      macroglobulin conjugate was internalized and transported into lysosomes of acid
      alpha-glucosidase-deficient fibroblasts. The enzyme activity was stable after
      being taken up by the cells. Uptake of the conjugate resulted in the degradation
      of glycogen accumulated in lysosomes. The alpha-galactosidase A-alpha 2
      macroglobulin conjugate was also internalized into the lysosomes of alpha
      galactosidase A-deficient fibroblasts. Internalized alpha-galactosidase A
      conjugate degraded globotriaosylceramide accumulated in lysosomes. The
      endocytosis of both conjugate was inhibited by alpha 2-macroglobulin-trypsin
      complex, indicating that the conjugates were endocytosed by an alpha 2
      macroglobulin receptor system. These results showed the usefulness of alpha 2
      macroglobulin as a transport vehicle of lysosomal enzymes for effective enzyme
      replacement.

PMID- 7525552
TI  - c phosphorylation and activation of the IGF-I receptor in src-transformed cells.
AB  - Using a panel of src mutants partially defective for malignant transformation,
      our laboratory has previously identified the insulin-like growth factor (IGF-I)
      receptor as a protein whose tyrosine phosphorylation correlates with
      transformation by src in embryonic chick cells (Kozma et al., 1990; Kozma and
      Weber, 1990). It has not been clear, however, whether src-induced phosphorylation
      altered the enzymatic or signaling properties of the IGF-I receptor and thus
      whether the IGF-I receptor could be a functionally significant target for pp60v
      src. To examine the effect of src expression on the activity of the IGF-I
      receptor, the human IGF-I receptor was expressed in Rat-1 fibroblasts co
      expressing the temperature-sensitive v-src mutant, tsLA29. The IGF-I receptor
      exhibited an elevated level of tyrosine phosphorylation in src transformed cells
      even in the absence of IGF-I treatment. Increased receptor phosphorylation
      occurred rapidly when cells expressing a temperature-conditional src mutant were
      shifted from the restrictive to the permissive temperature. Src-induced
      phosphorylation of the receptor was correlated with an increase in the in vitro
      tyrosine kinase activity of the receptor, both toward itself and exogenous
      substrates. The src-induced increase in receptor activity was shown to be
      dependent on tyrosine phosphorylation, as treatment with a tyrosine-specific
      phosphatase lowered receptor activity. A kinase-defective mutant of the IGF-I
      receptor also became constitutively phosphorylated in src-transformed cells,
      ruling out a possible autocrine mechanism for this phosphorylation. Collectively
      these data indicate that pp60v-src induces ligand-independent phosphorylation and
      activation of the IGF-I receptor by an intracellular mechanism, consistent with
      the possibility that receptor phosphorylation could contribute to the genesis of
      the transformed phenotype.

PMID- 7525551
TI  - Assessment of the contribution of the cytochrome b moiety of the NADPH oxidase to
      the transmembrane H+ conductance of leukocytes.
AB  - Phagocytic cells can kill microorganisms by synthesizing superoxide. Activation
      of the NADPH oxidase that generates superoxide is accompanied by a large
      intracellular burst of metabolic acid production. Despite the excess acid
      generation, cytosolic pH (pHi) remains near neutrality due to the concomitant
      stimulation of several homeostatic H+ extrusion mechanisms including a recently
      described H(+)-conductive pathway. Activation of the conductance by phorbol
      esters is defective in neutrophils of chronic granulomatous disease (CGD)
      patients lacking the transmembrane cytochrome b subunits of the NADPH oxidase.
      This finding suggests that the oxidase itself undertakes H+ translocation or
      that, alternatively, assembly of the oxidase is required to activate a separate
      H+ conducting entity. To distinguish between these possibilities, the presence of
      the conductive pathway was assessed in unstimulated normal and CGD cells by
      manipulating pHi and the transmembrane potential. Using fluorimetric
      determinations of pHi, a conductive, Zn(2+)-sensitive alkalinization was observed
      in neutrophils from both normal and cytochrome b-deficient CGD donors. The
      electrophysiological properties of the conductance were defined in purified blood
      monocytes using the whole cell configuration of the patch clamp. Depolarizing
      pulses induced slowly activating outward currents in cells from both normal and
      cytochrome b-deficient individuals. The elicited currents were potentiated by
      cytosolic acidification and did not inactivate within the times tested. As in
      control leukocytes, the reversal potential of tail currents in the CGD cells
      closely approximated the H+ equilibrium potential and was unaffected by
      substitution of the major ionic components of the external bathing medium. At all
      voltages tested, the magnitude of the evoked currents was comparable in normal
      and CGD cells. The results indicate that, like macrophages and granulocytes,
      human monocytes display a voltage-gated highly H(+)-selective conductance. More
      importantly, our findings imply that the conductive pathway is present in cells
      devoid of cytochrome b. Therefore, the defective activation of the conductive
      pathway by protein kinase C agonists in CGD cells is not due to the physical
      absence of the transporter. Instead we propose that the oxidase functions in a
      regulatory capacity, facilitating the opening of a distinct H+ conductance during
      cellular stimulation.

PMID- 7525553
TI  - Inhibition of mitochondrial protein synthesis promotes increased stability of
      nuclear-encoded respiratory gene transcripts.
AB  - To investigate the molecular basis of nuclear-mitochondrial communication, we
      have been studying the effect of mitochondrial stress (stimulated by inhibition
      of mitochondrial protein synthesis) on the homeostasis of transcripts encoding
      nuclear and mitochondrial gene products. We report that in cells treated with the
      inhibitor thiamphenicol, nuclear-encoded respiratory gene transcripts were
      dramatically stabilized. A concomitant up-regulation in the activity of the only
      known respiratory transcript binding protein, cytochrome c oxidase L-form
      transcript binding protein (COLBP), was also noted in thiamphenicol-treated
      cells, demonstrating a potential mechanism for the increased transcript
      protection. In contradistinction, stability of all mitochondrial RNAs was
      unaffected by the inhibitor, as were the nuclear-encoded beta-actin, alpha
      tubulin mRNAs and total cytosolic RNA. Steady state levels of all nuclear-encoded
      transcripts tested remained constant after inhibition of mitochondrial protein
      synthesis, whereas a generalized increase in the levels of processed
      mitochondrial mRNA was noted. We conclude that thiamphenicol induces (i) an
      increase in steady state levels of mitochondrial mRNA, (ii) a selective
      protection of nuclear respiratory gene transcripts against degradation, and (iii)
      an up-regulation in activity of the respiratory transcript binding protein COLBP,
      consistent with this protein mediating increased transcript stability. Our
      results demonstrate a coordinated series of intracellular responses to
      thiamphenicol-induced mitochondrial stress, regulated at both the pre- and post
      transcriptional levels.

PMID- 7525554
TI  - Adenosine A3 receptors regulate serotonin transport via nitric oxide and cGMP.
AB  - Many antidepressants inhibit 5-hydroxytryptamine (5HT) transport resulting in
      increased 5HT levels in the synapse. However, physiological regulation of
      neurotransmitter uptake has not been demonstrated. We have examined the effect of
      receptor-activated second messengers on the 5HT transporter in rat basophilic
      leukemia cells (RBL 2H3). Here, we show that activation of an A3 adenosine
      receptor results in an increase of 5HT uptake in RBL cells, due to an increase in
      maximum velocity (Vmax). The A3 adenosine receptor-stimulated increase in
      transport is blocked by inhibitors of nitric oxide synthase and by a cGMP
      dependent kinase inhibitor. In fact, compounds that generate nitric oxide (NO)
      and the cGMP analog 8-bromo-cGMP mimicked the effect of A3 receptor stimulation,
      suggesting that the elevation in transport occurs through the generation of the
      gaseous second messenger NO and a subsequent elevation in cGMP. Additionally, the
      5HT transporter is differentially regulated by second messengers since direct
      activation of protein kinase C by phorbol esters decreases 5HT uptake by
      decreasing Vmax. Our results suggest that the changes in transport are due to a
      direct modification of the 5HT transporter, possibly by phosphorylation, which
      appears to alter the rate at which transport occurs. As the 5HT transporter in
      RBL cells is identical to that in neurons, our results suggest that analogous
      mechanisms may operate in the brain.

PMID- 7525555
TI  - Activation of Src family kinase activity by the G protein-coupled thrombin
      receptor in growth-responsive fibroblasts.
AB  - Thrombin stimulates G protein-coupled signaling pathways in target cells by
      proteolytic cleavage of its seven transmembrane domain receptor. Protein tyrosine
      phosphorylation is also stimulated by the protease via poorly defined mechanisms.
      In human platelets, thrombin has been shown to activate the nonreceptor tyrosine
      kinase Src. To elucidate the signal transduction pathways involved in
      transmission of thrombin's cellular effects, we have examined the ability of
      thrombin to activate Src family tyrosine kinases in a growth-responsive line of
      lung fibroblasts (CCL39 cells). We report here that thrombin induces a rapid (<
      or = 30 s) and transient increase in the kinase activity of Src and Fyn as
      determined by autophosphorylation in immune complex kinase assays. Activation is
      mediated by the G protein-coupled thrombin receptor since a synthetic peptide
      agonist of the receptor mimics thrombin action. The involvement of one or more G
      proteins in this response was confirmed by the observation that thrombin's effect
      is partially sensitive to pertussis toxin. Furthermore, both alpha 2-adrenergic
      and muscarinic m1 receptors are able to increase Src kinase activity via
      pertussis toxin-sensitive and -insensitive G proteins, respectively. These
      findings suggest that nonreceptor tyrosine kinases of the Src family may
      represent a novel effector system linking G protein-coupled receptors to
      downstream activation of Ras and the mitogen-activated protein kinase cascade.

PMID- 7525556
TI  - Differential tyrosine phosphorylation of JAK1, JAK2, and STAT1 by growth hormone
      and interferon-gamma in IM-9 cells.
AB  - Both the growth hormone (GH) and interferon gamma (IFN gamma) receptors are
      members of the cytokine receptor family that activate tyrosine phosphorylation
      despite the lack of a tyrosine kinase domain. Recently, the Janus kinase (JAK)
      family of tyrosine kinases have been shown to play an integral role in
      intracellular signaling by the cytokine receptors. We demonstrate that, in the
      human IM-9 lymphocyte, both JAK1 and JAK2 are tyrosine-phosphorylated in response
      to IFN gamma, whereas only JAK2 is tyrosine-phosphorylated in response to GH.
      Furthermore, dimerization of the GH receptor appears to be necessary for GH
      stimulated tyrosine phosphorylation of JAK2. We provide two lines of evidence
      that the JAK2 kinases can be regulated independently by GH and IFN gamma in IM-9
      cells: 1) desensitization of JAK2 to GH stimulation does not affect the IFN gamma
      stimulated tyrosine phosphorylation of JAK2; and 2) JAK2 tyrosine phosphorylation
      by GH and IFN gamma is additive to that seen with either hormone alone.
      Furthermore, we demonstrate that although IFN gamma activates the tyrosine
      phosphorylation of the p91 signal transducer and activator of transcription
      (STAT1) in IM-9 cells, GH does not. GH does activate the tyrosine phosphorylation
      of a 93-kDa protein that appears to be distinct from STAT1.

PMID- 7525557
TI  - Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes.
      Characterization and regulation of iNOS expression and detection of iNOS activity
      in single cardiac myocytes in vitro.
AB  - Cellular constituents of heart muscle contain both constitutive and inducible
      nitric oxide (NO) signaling pathways that modulate the contractile properties of
      cardiac myocytes. The identities of the inducible NO synthase (iNOS) isoform(s)
      expressed in cardiac muscle, and of the specific cell types expressing iNOS
      activity, remain poorly characterized. We amplified a 217-base pair cDNA by
      reverse transcriptase-polymerase chain reaction from primary cultures of
      inflammatory cytokine-pretreated adult rat ventricular myocytes (ARVM) that was
      nearly identical to other iNOS cDNA sequences. Using this 217-base pair cDNA as a
      probe in Northern blots, we found no evidence of iNOS mRNA in control myocytes,
      but both interleukin-1 beta and interferon-gamma individually increased iNOS mRNA
      abundance in primary cultures of ARVM, with maximal expression at 12 h. The half
      life of iNOS mRNA in actinomycin C1-treated cells was 4 h. Both dexamethasone and
      transforming growth factor-beta attenuated the induction of iNOS mRNA abundance
      and enzyme activity by IL-1 beta and INF gamma. Pretreatment with dexamethasone
      also abolished the induction of iNOS mRNA, but not the increase in GTP
      cyclohydrolase mRNA in purified cardiac myocytes from lipopolysaccharide-injected
      rats. In order to further characterize the specific cell type producing NO, we
      used a NO-specific porphyrinic/Nafion-coated microsensor to record NO release
      from a single, isolated ARVM pretreated with IL-1 beta and IFN gamma in L
      arginine-depleted medium. NO release could be detected following microinjection
      of L-arginine in the vicinity of the cell juxtaposed to the NO microsensor, but
      not following microinjection of D-arginine, and not from ARVM pretreated with L-N
      monomethylarginine. Cytokine-pretreated ARVM that had been maintained in L
      arginine-depleted medium also exhibited a depressed contractile response to
      isoproterenol after addition of L-arginine, but not D-arginine. These results
      indicate that altered contractile function of cardiac myocytes following exposure
      to specific inflammatory cytokines is due to induction of myocyte iNOS.

PMID- 7525558
TI  - Sphingosine induces p125FAK and paxillin tyrosine phosphorylation, actin stress
      fiber formation, and focal contact assembly in Swiss 3T3 cells.
AB  - Treatment of Swiss 3T3 cells with sphingosine, a potential breakdown product of
      all sphingolipids, induced tyrosine phosphorylation of multiple substrates
      including bands of M(r) 110,000-130,000 and M(r) 70,000-80,000. Tyrosine
      phosphorylation in response to sphingosine occurred in a concentration dependent
      manner (EC50 = 10 microM) and developed gradually reaching half maximum and
      maximum effects at 20 and 60 min, respectively. The dihydroenantiomere of
      sphingosine, DL-threo-dihydrosphingosine, neither induced tyrosine
      phosphorylation nor interfered with sphingosine-stimulated tyrosine
      phosphorylation. Focal adhesion kinase (p125FAK) and paxillin were identified as
      prominent substrates for sphingosine-stimulated tyrosine phosphorylation. Cell
      permeable ceramides also stimulated tyrosine phosphorylation of the M(r) 110,000
      130,000 band as well as p125FAK, but the effect was less pronounced than that of
      sphingosine. Tyrosine phosphorylation by sphingosine could be dissociated from
      both protein kinase C activation and Ca2+ mobilization from intracellular stores.
      Sphingosine stimulated striking actin stress fiber formation and focal adhesion
      assembly in Swiss 3T3 cells. The kinetics of actin stress fiber formation and
      tyrosine phosphorylation in response to sphingosine closely paralleled.
      Cytochalasin D, which disrupts the network of actin microfilaments, completely
      inhibited sphingosine induced tyrosine phosphorylation. In addition, tyrosine
      phosphorylation of p125FAK and paxillin in response to sphingosine was completely
      prevented when cells were stimulated in the presence of platelet-derived growth
      factor at a concentration (30 ng/ml) that caused disruption of the actin
      cytoskeleton. Our results demonstrate, for the first time, that sphingosine
      induces p125FAK and paxillin tyrosine phosphorylation, actin stress fiber
      formation and focal adhesion assembly in Swiss 3T3 cells.

PMID- 7525559
TI  - In vitro complex formation between the octamer of mitochondrial creatine kinase
      and porin.
AB  - An interaction of mitochondrial creatine kinase with purified outer mitochondrial
      porin (voltage-dependent anion channel) was shown by co-sedimentation assays as
      well as by gel permeation chromatography. Porin formed high M(r) complexes with
      wild-type mitochondrial creatine kinase as well as with an N-terminal deletion
      mutant, lacking the first five N-terminal amino acids. The complexes were
      identified by creatine kinase activity in parallel with immunoblotting using
      specific antibodies against the two proteins. In addition, porin induced
      octamerization of the N-terminal creatine kinase mutant, which under the same
      conditions without porin, did not polymerize but remained more than 90% dimeric.
      Furthermore, binding of mitochondrial creatine kinase to porin affected the
      conductance of porin when reconstituted in "black membranes." At 10 mV the pore
      in the complex adopted a low conductance (1.5-2 nanosiemens) state, compared to
      the high conductance state (3-4 nanosiemens) of the free incorporated pores. The
      former state of the pore is known to be cationically selective. Thus, besides a
      specific structural interaction, a defined physiological function is assumed of
      the mitochondrial creatine kinase-porin complexes that are discussed here.

PMID- 7525560
TI  - A sialoglycoprotein from human leukocytes functions as a ligand for P-selectin.
AB  - P-selectin (CD62P), a Ca(2+)-dependent lectin expressed on activated platelets
      and endothelial cells, functions as a receptor for myeloid and monocytoid cells.
      Previous reports have described a homodimeric sialoglycoprotein from human
      leukocytes and HL-60 cells specifically recognized by P-selectin. We describe
      here a panel of monoclonal antibodies prepared against high molecular weight
      fractions of HL-60 cell membranes. These antibodies are of IgM isotype, bind to a
      approximately 240-kDa protein from human leukocyte membranes which is also
      reactive with P-selectin. They recognize a Ca(2+)-dependent, sialidase-sensitive
      determinant on myeloid and monocytoid cell lines. Each antibody specifically
      inhibits adhesion of neutrophils or HL-60 cells to: 1) purified P-selectin, 2)
      thrombin-stimulated platelets, and 3) phorbol 12-myristate 13-acetate-activated
      endothelial cells. These results suggest that the sialoglycoprotein recognized by
      this panel of monoclonal antibodies may function as a cell surface ligand for P
      selectin.

PMID- 7525561
TI  - Identification of the regulatory domain of the mammalian multifunctional protein
      CAD by the construction of an Escherichia coli hamster hybrid carbamyl-phosphate
      synthetase.
AB  - Carbamyl-phosphate synthetases from different organisms have similar catalytic
      mechanisms and amino acid sequences, but their structural organization, sub-unit
      structure, and mode of regulation can be very different. Escherichia coli
      carbamyl-phosphate synthetase (CPSase), a monofunctional protein consisting of
      amido-transferase and synthetase subunits, is allosterically inhibited by UMP and
      activated by NH3, IMP, and ornithine. In contrast, mammalian CPSase II, part of
      the large multifunctional polypeptide, CAD, is inhibited by UTP and activated by
      5-phosphoribosyl-1-pyrophosphate (PRPP). Previous photoaffinity labeling studies
      of E. coli CPSase showed that allosteric effectors bind near the carboxyl
      terminal end of the synthetase subunit. This region of the molecule may be a
      regulatory subdomain common to all CPSases. An E. coli mammalian hybrid CPSase
      gene has been constructed and expressed in E. coli. The hybrid consists of the E.
      coli CPSase synthetase catalytic subdomains, residues 1-900 of the 1073 residue
      polypeptide, fused to the amino-terminal end of the putative 190-residue
      regulatory subdomain of the mammalian protein. The hybrid CPSase had normal
      activity, but was no longer regulated by the prokaryotic allosteric effectors.
      Instead, the glutamine- and ammonia-dependent CPSase activities and both ATP
      dependent partial reactions were activated by PRPP and inhibited by UTP,
      indicating that the binding sites of both of these ligands are located in a
      regulatory region at the carboxyl-terminal end of the CPSase domain of CAD. The
      apparent ligand dissociation constants and extent of inhibition by UTP are
      similar in the hybrid and the wild type mammalian protein, but PRPP binds 4-fold
      more weakly to the hybrid. The allosteric ligands affected the steady state
      kinetic parameters of the hybrid differently, suggesting that while the linkage
      between the catalytic and regulatory subdomains has been preserved, there may be
      qualitative differences in interdomain signal transmission. Nevertheless,
      switching prokaryotic and eukaryotic allosteric controls argues for remarkable
      conservation of structure and regulatory mechanisms in this family of proteins.

PMID- 7525562
TI  - Rescue and activation of a binding-deficient insulin receptor. Evidence for
      intermolecular transphosphorylation.
AB  - Binding of insulin to the alpha subunit of the insulin receptor (IR) leads to
      autophosphorylation of the beta subunit. The reaction proceeds as intramolecular
      transphosphorylation between alpha beta half-receptors of the heterotetrameric
      receptor dimer (alpha 2 beta 2). Since IRs are mobile in the plane of the plasma
      membrane, it is also possible that transphosphorylation may occur between
      adjacent holoreceptors (alpha 2 beta 2) by an intermolecular reaction. To address
      this question, we cotransfected NIH-3T3 cells with two IR cDNA constructs: a
      truncated but functionally normal IR lacking the C-terminal 43 amino acids (delta
      43) and a full-length Leu323 mutant receptor that is expressed on the cell
      surface but that does not bind insulin. A clonal cell line was selected from
      cells cotransfected with a 1/5 ratio of delta 43 cDNA/Leu323 cDNA. The two
      homodimers (Leu323 and delta 43) were expressed without detectable formation of
      hybrid receptors. By using specific antibodies, we demonstrate that in cells
      coexpressing both homodimers, the Leu323 mutant receptor was phosphorylated in
      vivo by the delta 43 IR in an insulin-dependent manner. However, when the Leu323
      mutant receptor was expressed alone, no phosphorylation was detected. In
      addition, we demonstrate the association of the phosphorylated Leu323 mutant
      receptor with insulin receptor substrate-1 and with phosphatidylinositol 3
      kinase. These findings indicate that insulin binding is not required for
      phosphorylation of the Leu323 mutant receptor, that the phosphorylation of the
      Leu323 mutant receptor occurs by an intermolecular transphosphorylation
      mechanism, and, finally, that the Leu323 mutant receptor, once phosphorylated,
      can associate with insulin receptor substrate-1 and phosphatidylinositol 3
      kinase.

PMID- 7525564
TI  - High agonist-independent activity is a distinguishing feature of the dopamine D1B
      receptor subtype.
AB  - Dopamine D1A and D1B receptor subtypes belong to the superfamily of G protein
      coupled receptors. Both receptors are coupled to the activation of adenylyl
      cyclase and exhibit distinct brain distribution. To identify functional
      differences, binding and stimulation of adenylyl cyclase were assessed in 293
      cells expressing transiently either dopamine D1A or D1B receptors. Membranes
      expressing D1B receptors displayed higher affinities for agonists than those
      expressing D1A receptors, whereas antagonist affinities were lower at the D1B
      than at the D1A receptor. Basal activity of adenylyl cyclase in whole 293 cells
      expressing various levels of D1B receptors was significantly higher than the
      basal activity measured in cells expressing D1A receptors. Maximal activation of
      adenylyl cyclase resulting from stimulation of the D1B receptor was less than
      that obtained following agonist activation of the D1A receptor. In cells
      expressing D1B receptors, agonists displayed an increased potency for stimulating
      adenylyl cyclase in comparison with the potencies determined for the D1A
      receptor. On the other hand, certain antagonists displayed "negative efficacy" at
      both receptor subtypes but had a more profound inhibition on the agonist
      independent signaling activity of the D1B receptor. The properties described here
      are reminiscent of those of constitutively active G protein-coupled receptors
      obtained by site-directed mutations. Thus, the D1B receptor may represent a
      naturally occurring receptor subtype with properties akin to those of
      constitutively active G protein-coupled receptors. The different anatomical
      distribution and biochemical properties of these D1 receptors strengthen the
      functional distinctions between the two subtypes and could account for the basis
      of heterogeneity within a given class of neurotransmitter or hormone receptors.
      In addition, if these properties are recapitulated in cells expressing the D1B
      receptors, they may underlie important role in the regulation of physiological
      effects by dopamine. Finally, these results raise the interesting possibility
      that psychotropic antagonist drugs used in the management of certain brain
      disorders may have their beneficial actions as negative efficacy compounds.

PMID- 7525565
TI  - Expressing murine beta 1,4-galactosyltransferase in HeLa cells produces a cell
      surface galactosyltransferase-dependent phenotype.
AB  - Beta 1,4-Galactosyltransferase is traditionally viewed as a biosynthetic
      component of the Golgi complex, but a portion of galactosyltransferase is also
      expressed on the cell surface, where it has been suggested to function as a
      receptor for extracellular oligosaccharide ligands. Although results from a
      variety of studies are consistent with a cell adhesion function for
      galactosyltransferase, the most rigorous test of surface galactosyltransferase
      function is to produce a surface galactosyltransferase-dependent phenotype in
      cells that normally express negligible levels of surface galactosyltransferase.
      In agreement with previous reports, human HeLa cells were found to express low
      levels of galactosyltransferase on their surface and, therefore, were stably
      transfected with cDNAs encoding murine galactosyltransferase. Murine
      galactosyltransferase was expressed both within the presumed Golgi complex and on
      the cell surface, as assayed by enzyme activity and with antiserum raised against
      the bacterially expressed murine enzyme. HeLa cell transfectants adhered more
      strongly to their extracellular substrates than did control transfectants, as
      evidenced by a flatter morphology in culture and a more rapid spreading upon
      plating. In contrast, cell spreading was low and similar among all cell types
      when plated on extracellular substrates that did not contain binding sites for
      galactosyltransferase. Antibodies and Fab fragments against recombinant murine
      galactosyltransferase inhibited the increased cell spreading characteristic of
      galactosyltransferase transfectants, as did soluble recombinant
      galactosyltransferase and a variety of galactosyltransferase perturbants. Thus,
      expression of heterologous galactosyltransferase produces a surface
      galactosyltransferase-dependent phenotype, confirming its function as a cell
      adhesion molecule.

PMID- 7525563
TI  - Insulin receptor substrate 1 mediates the stimulatory effect of insulin on GLUT4
      translocation in transfected rat adipose cells.
AB  - Insulin signaling is initiated at least in part by activation of the insulin
      receptor tyrosine kinase and subsequent phosphorylation of cellular substrates
      such as insulin receptor substrate 1 (IRS-1). Previous studies have focused on
      the role of IRS-1 in the mitogenic actions of insulin. We have now investigated
      the possible role of IRS-1 in mediating the effect of insulin to stimulate
      glucose transport in a physiologically relevant insulin target tissue. In this
      study, we transfected rat adipose cells in primary culture with an antisense
      ribozyme directed against rat IRS-1. Expression of the ribozyme in these cells
      caused a 4.4-fold increase in the concentration of insulin required to achieve
      half-maximal stimulation of the translocation of cotransfected epitope-tagged
      GLUT4 without changing the maximal insulin response. Overexpression of human IRS
      1 increased the basal cell surface GLUT4 to nearly the maximal level in the
      absence of insulin. When the ribozyme (specific to rat IRS-1) was cotransfected
      along with human IRS-1, the insulin dose-response curve was shifted to the left
      when compared with cells transfected with the ribozyme alone. These data provide
      strong support for the hypothesis that IRS-1 plays a role in insulin-stimulated
      glucose transport in insulin-responsive cells.

PMID- 7525566
TI  - Structure/function studies of human immunodeficiency virus type 1 reverse
      transcriptase. Alanine scanning mutagenesis of an alpha-helix in the thumb
      subdomain.
AB  - Human immunodeficiency virus type 1 reverse transcriptase has subunits of 66 and
      51 kDa (p66 and p51, respectively). Structural studies indicate that each subunit
      consists of common subdomains. The polymerase domain of p66 forms a nucleic acid
      binding cleft, and, by analogy with a right hand, the subdomains are referred to
      as fingers, palm, and thumb (Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice,
      P. A., and Steitz, T. A. (1992) Science 256, 1783-1790). Residues 257-266
      correspond to a highly conserved region of primary structure among retroviral pol
      genes. Crystallographic evidence indicates that these residues are in the thumb
      subdomain and form part of an alpha-helix (alpha H), which interacts with DNA
      (Jacobo-Molina, A., Ding, J., Nanni, R. G., Clark, A. D., Jr., Lu, X., Tantillo,
      C., Williams, R. L., Kamer, G., Ferris, A. L., Clark, P., Hizi, A., Hughes, S.
      H., and Arnold, E. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 6320-6324). To
      define the role of this region during catalytic cycling, we performed systematic
      site-directed mutagenesis from position 253 through position 271 by changing each
      residue, one by one, to alanine. Each mutant protein was expressed and purified,
      and their substrate-specific activities were surveyed. The results are consistent
      with alpha H (residues 255-268) of p66 interacting with the template and/or
      primer strand. The core of alpha H appears to play an important role in template
      primer binding (residues Gln-258, Gly-262, and Trp-266), and in protein-protein
      interactions (residues Val-261 and Leu-264). The periodicity of the effects
      observed suggest that a segment of one face of alpha H interacts with the
      template-primer. The lower fidelity observed with alanine mutants of Gly-262 and
      Trp-266 correlated with an over 200-fold increase in the dissociation rate
      constant for template-primer relative to wild type enzyme and suggests that
      enzyme-DNA interactions in the template-primer stem are important fidelity
      determinants.

PMID- 7525567
TI  - The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2', 3'
      dideoxycytidine, 2',3'-dideoxy-3'-thiacytidine, and 2',3'-dideoxyinosine shows
      reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in
      vitro.
AB  - The K65R mutation in human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) encodes cross-resistance to 2',3'-dideoxycytidine (ddC), 2',3'
      dideoxy-3'-thiacytidine (3TC), and 2',3'-dideoxyinosine (ddI). We characterized
      the in vitro sensitivities of recombinant wild type (wt) and K65R mutant RT to
      dideoxynucleoside triphosphate (ddNTP) inhibitors, using a variety of primer
      templates. With poly(rA)-oligo(dT), the K65R mutant showed slight increases in Ki
      for ddTTP and 3'-azido, 3'-deoxythymidine triphosphate (AZTTP) compared to wt RT,
      but neither wt nor K65R RT was inhibited by ddCTP or ddATP. With poly(rI)
      oligo(dC), the K65R mutant showed a 2-fold increase in Km for dCTP and a 20-fold
      increase in Ki for ddCTP compared to wt, whereas ddATP, ddTTP, and AZTTP failed
      to inhibit either enzyme. With a heteropolymeric primer-template, the K65R mutant
      showed 10-fold reduced sensitivities to ddCTP, 3TCTP, and ddATP, and 4-fold
      reduced sensitivity to AZTTP, compared to wt. In contrast, both enzymes were
      equally inhibited by ddTTP and ddGTP. HIV-1 cross-resistance to ddC/3TC/ddI
      resulting from the K65R mutation may therefore involve selective alterations in
      substrate/inhibitor recognition. Additionally, competitive inhibition by ddNTPs
      noncomplementary to the template base appears to be unimportant in the mechanism
      of inhibition of HIV-1 RT by dideoxynucleoside analogs.

PMID- 7525568
TI  - Interactions of Lyn with the antigen receptor during B cell activation.
AB  - Signaling through the B cell antigen receptor requires a complex set of
      interactions involving transmembrane components of the IgM receptor complex and
      cytosolic protein-tyrosine kinases. We have focused on the nature of these
      protein-protein interactions, the requirements for their occurrence, as well as
      the temporal sequence of events during the activation process. We found that
      cross-linking B cell antigen receptors at 0 degree C resulted in the rapid
      association of the Src-family protein-tyrosine kinase, Lyn, with the antigen
      receptor complex as judged by the presence of Lyn in anti-IgM and anti
      phosphotyrosine immune complexes and the presence of MB-1 in anti-Lyn immune
      complexes. Receptor engagement also resulted in the rapid association of Lyn with
      the phosphotyrosine phosphatase, CD45. This association of Lyn with receptor
      components was stable in the detergent Brij 96, but was readily disrupted by
      Nonidet P-40, suggesting the involvement of hydrophobic interactions in
      stabilizing formation of the Lyn-receptor complex. The protein-tyrosine kinase,
      Syk, was also found associated with activated receptor complexes. This
      association of Syk with components of the antigen receptor complex was stable to
      Nonidet P-40. Antibodies directed against the carboxyl teminus of Syk, but not
      against the amino-terminal SH2 domain, co-immunoprecipitated MB-1 from activated
      cells, consistent with the binding of Syk through an SH2 domain-phosphotyrosine
      interaction.

PMID- 7525569
TI  - Mutations along transmembrane segment II of the NK-1 receptor affect substance P
      competition with non-peptide antagonists but not substance P binding.
AB  - Mutational analysis of the NK-1 receptor indicates that residues involved in non
      peptide antagonist binding cluster around the outer portion of transmembrane
      segments (TM) V and VI. In contrast mutations affecting the binding of the
      natural peptide agonist, substance P, are scattered in the exterior part of the
      receptor. Recently it was reported that a number of mutations in TM-II also
      seriously impair substance P binding. Here we confirm that Ala substitutions for
      these residues located on a hydrophilic helical face of TM-II basically eliminate
      substance P binding to the NK-1 receptor, provided that a radiolabeled non
      peptide antagonist is used as radioligand. Surprisingly, radiolabeled substance P
      bound well to all these mutant receptors and was displaced with only slightly
      reduced affinity by the unlabeled peptide and by the non-peptide antagonists. The
      wild-type homologous NK-2 receptor displayed properties similar to those observed
      in the mutated NK-1 receptors, i.e. concomitant high affinity binding of
      radiolabeled agonist peptide (in this case neurokinin A), yet low affinity, G
      protein independent competition of unlabeled peptide with radiolabeled non
      peptide antagonist. It is concluded that substitutions in TM-II of the NK-1
      receptor do not affect the high affinity binding of substance P but instead block
      the ability of the peptides to compete for non-peptide antagonist binding. It is
      suggested that certain mutations can impair interchange between receptor
      conformations that each bind different ligands with high affinity.

PMID- 7525570
TI  - Tumor growth and angiogenesis induced by a secreted binding protein for
      fibroblast growth factors.
AB  - Basic fibroblast growth factor (bFGF) is a strong inducer of angiogenesis and
      thus may play an important role in the growth of solid tumors. However, bFGF is
      usually found immobilized on the extracellular matrix, and it is only partly
      understood how it is solubilized to reach and activate its extracellular
      receptors. We studied the potential contribution to this process by a secreted
      binding protein (BP) with high affinity for FGFs. An expression vector for BP was
      transfected into a human cell line (SW-13) that contains constitutively high
      levels of bFGF. The BP-expressing cells began to grow colonies in soft agar due
      to their autocrine stimulation by bFGF and released biologically active bFGF into
      their media. Furthermore, they grew into well vascularized tumors in athymic nude
      mice. In addition, we found the BP mRNA expressed at high levels in squamous cell
      carcinoma (SCC) tissues from patients and in SCC cell lines of different origin
      as well as in immortalized keratinocytes. However, we failed to detect BP mRNA in
      normal adult tissues or in a number of non-SCC tumor cell lines. Expression of
      the secreted BP appears to be a mechanism through which immobilized FGF can be
      activated to support tumor growth and angiogenesis.

PMID- 7525572
TI  - Proteins of the inter-alpha-trypsin inhibitor family stabilize the cumulus
      extracellular matrix through their direct binding with hyaluronic acid.
AB  - We have previously identified a glycoprotein of the inter-alpha-trypsin inhibitor
      family of proteins as a serum factor responsible for the stabilization of the
      expanding cumulus mass. In this study, the mechanism of interaction of this
      cumulus extracellular matrix stabilizing factor (cESF) with hyaluronic acid (HA)
      has been explored. It was found that the pH optimum for binding of cESF and HA is
      7 and that binding is sensitive to ionic strength. The dissociation constant is
      about 1.9 x 10(-8) M in 10 mM sodium phosphate buffer (pH 7.2). Circular
      dichroism studies show that cESF contains about 24% alpha-helical and 42% beta
      sheet structure. Gross conformational changes in cESF, however, are not detected
      in the presence of HA. We also found that modification of lysine residues of cESF
      with citraconic anhydride greatly reduced its binding with HA and completely
      abolished its cumulus stabilizing activity, and deblocking lysine residues
      restored its capacity to bind with HA and its cumulus matrix stabilizing
      activity. This evidence supports the hypotheses that cESF stabilizes the
      expanding cumulus extracellular matrix by directly binding with HA and that cESF
      may serve as a structural protein to organize the formation of the cumulus
      extracellular matrix. Our evidence also supports the view that binding of cESF
      and HA is through a stereo-specific charge interaction. Putative binding sites of
      cESF that interact with HA are postulated.

PMID- 7525571
TI  - Studies on the membrane topology of the (Na,K)-ATPase.
AB  - The topology of the alpha 1 and beta 1 subunits of the rat (Na,K)-ATPase has been
      studied by insertion of epitope(s): at the NH2 terminus and COOH terminus and
      between Glu-117 and Glu-118, Lys-828 and Arg-829, Gln-900 and Trp-901, and Val
      939 and Phe-940 of the alpha subunit; and at the NH2 terminus and COOH terminus
      and between Glu-228 and Tyr-229 of the beta subunit. The epitope-tagged alpha 1
      constructs were expressed in HeLa cells to select for stable cell lines
      expressing a functional (Na,K)-ATPase. The epitope-tagged beta constructs were
      transiently expressed in Cos-7 cells. The membrane arrangement of the epitopes
      was revealed by indirect immunofluorescence with cells expressing the (Na,K)
      ATPase chains. The results indicate that the alpha subunit has 4 transmembrane
      segments in the COOH-terminal membrane-bound domain between residues 760 and 938,
      and that both the NH2 terminus and the COOH terminus are in the cytosol; it was
      not determined whether there are more transmembrane segments between residue 938
      and the COOH terminus. The beta subunit has only one transmembrane-spanning
      region with the NH2 terminus in the cytosol and the COOH terminus on the
      extracytoplasmic surface of the plasma membrane.

PMID- 7525573
TI  - Isolation of an immunodominant IgE hapten from an epitope expression cDNA
      library. Dissection of the allergic effector reaction.
AB  - An epitope expression cDNA library was constructed from the randomly fragmented
      cDNA coding for Phl p I, the major grass pollen allergen. Using IgE from allergic
      patients, epitope clones were isolated and immunodominant fragments were
      selected. Among three epitope clones coding for a similar region of Phl p I, one
      clone expressed a 15-amino-acid epitope which was target for IgE antibodies from
      approximately 30% of grass pollen allergic patients. According to the prevalence
      of grass pollen allergy, 22% of all allergic patients are expected to display IgE
      reactivity with this epitope. Although the purified recombinant epitope
      specifically bound IgE, it did not release histamine from basophiles of most
      grass pollen allergic patients and thus represents an IgE hapten. Immunodominant
      IgE haptens may be useful as therapeutic agents to saturate mast cell-bound IgE
      prior to allergen exposure and may represent candidates for a safe immunotherapy
      of allergic diseases by reducing anaphylactic side effects.

PMID- 7525574
TI  - Functional importance of an Sp1- and an NFkB-related nuclear protein in a
      keratinocyte-specific promoter of rabbit K3 keratin gene.
AB  - We have shown previously that a 300-base pair (bp) 5' upstream sequence of rabbit
      keratin K3 gene (RK3) can function as a keratinocyte-specific promoter in
      transient transfection assays. Electrophoretic mobility shift assays using
      various overlapping and mutated oligonucleotides established that corneal
      keratinocyte nuclear proteins bound in vitro to two sites (B and E).
      Immunosupershift and UV cross-linking established that the keratinocyte nuclear
      binding protein of site B (5'-GGGGCTTTCC-3', -262 to -253 bp) was NFkB consisting
      of the p65 and p50 subunits. The E site contained an unusual GC-rich motif (5'
      CCGCCCCCTG-3', -203 to -194 bp) whose sequence deviated from the Sp1 consensus in
      4 out of 10 positions; this site bound an Sp 1-related keratinocyte nuclear
      protein. Mutagenesis of the NFkB, GC motif, and both sites abolished 20, 50, and
      75%, respectively, of the promoter activity in transfected keratinocytes. The
      NFkB-like keratinocyte nuclear protein was barely detectable in kidney epithelial
      cells, HeLa, and fibroblasts. The Sp1-related nuclear protein was abundant in
      keratinocytes and simple epithelial cells, but was much less abundant in
      fibroblasts. These results indicate that NFkB is present in significant
      quantities in keratinocyte nuclei and that the tissue restriction of the NFkB-
      and Sp1-related proteins, in combination with other factors, may contribute to
      the keratinocyte specificity of RK3 promoter.

PMID- 7525575
TI  - Rupture of the mitochondrial outer membrane impairs porin assembly.
AB  - Outer membranes isolated from yeast mitochondria were capable mediating the in
      vitro insertion of porin. As with the outer membrane of intact mitochondria, the
      insertion was ATP-dependent, and the inserted porin was resistant to trypsin
      treatment after detergent solubilization. However, the extent of porin insertion
      into isolated outer membranes was much less per mg of outer membrane protein than
      with intact mitochondria. The greater efficiency of intact mitochondria was not
      due to contact site-mediated translocation as isolated contact sites were less
      able to insert porin than isolated outer membranes, and blockade of the contact
      site channel in intact mitochondria did not affect porin insertion. However,
      mitochondria that had been subjected to osmotic shock sufficient to rupture the
      outer membrane and deplete the contents of the intermembrane space (i.e.
      mitoplasts) lost most of their ability to insert porin. Since outer membranes are
      isolated from mitoplasts, the low insertion activity of mitoplasts explains the
      low efficiency of insertion into isolated outer membranes. These results also
      indicate that, unlike proteins that are imported to the inner membrane and matrix
      of the mitochondria, porin's assembly is severely reduced by breaching the outer
      membrane and depletion of the intermembrane space contents.

PMID- 7525577
TI  - Deoxynucleotide polymerization by HIV-1 reverse transcriptase is terminated by
      site-specific styrene oxide adducts after translesion synthesis.
AB  - In an effort to integrate an understanding of human immunodeficiency virus type 1
      (HIV-1) reverse transcriptase (RT) structure with its function, the action of HIV
      1 RT was examined in vitro on DNA templates modified with a model bulky DNA
      adduct. Styrene oxide was site-specifically and stereospecifically coupled to the
      N6 position of adenine to form six different adducted templates. Primer extension
      assays were conducted under conditions defining both single and multiple
      encounters between the polymerase and the damaged template-primer. The extent of
      polymerization observed for each adduct was found to depend on both the chirality
      of the damage and the lesion sequence context. When HIV-1 RT polymerization was
      limited by single encounters with damaged DNA, the SO lesions were readily
      bypassed as evidenced by minimal pausing at the adducted base. However, RT
      replication of all SO-modified templates was significantly terminated 3-5
      nucleotides after translesion synthesis but before reaching the end of the
      template. These truncated products could be readily extended when additional
      encounters between enzyme and template-primer were permitted. A model is
      presented to explain these results in the context of HIV-1 RT structure during
      DNA replication.

PMID- 7525576
TI  - Carboxyl terminus of inducible nitric oxide synthase. Contribution to NADPH
      binding and enzymatic activity.
AB  - Cloning of a nitric oxide synthase (NOS) from RAW 264.7 mouse macrophages (Xie,
      Q.-w., Cho, H. J., Calaycay, J., Mumford, R. A., Swiderek, K. M., Lee, T. D.,
      Ding, A., Troso, T., and Nathan, C. (1992) Science 256, 225-228) yielded two sets
      of cDNA: one with a longer coding region of 1144 amino acids, whose sequence
      matched that of the purified protein, and another with a shorter coding region of
      1122 amino acids, in which the last 10 carboxyl-terminal amino acids differed
      completely from those of the long form. We have now found that the short form
      lacks NOS activity. To determine the basis of this defect, we prepared
      recombinant chimeric, deletional, and point mutants of the long and short NOS
      variants, monitored their expression by immunoblot, and tested their enzymatic
      activity. By itself, lack of the 22-carboxyl-terminal residues of the long form
      NOS was scarcely consequential. Mutation of Phe1122, the only aromatic residue
      within one of the longest conserved regions shared by all NOSs of reported
      sequence, reduced enzymatic activity by 41%. Deletion of 23 carboxyl-terminal
      amino acids (including Phe1122) reduced activity by 71%. Further loss of Ile1121,
      another completely conserved residue, reduced activity by 95%, and with the
      deletion of the rest of the conserved region, NOS activity was undetectable.
      Normal dimerization and binding of heme and calmodulin by the short variants
      militated against distortions of tertiary structure affecting the amino-terminal
      half or middle portion of the protein. In contrast, the short variants were
      deficient in binding to NADPH, as predicted by a model of tertiary structure
      based on that of spinach ferredoxin-NADP+ reductase. This is the first
      demonstration that the carboxyl terminus of NOS is a functionally critical
      region.

PMID- 7525578
TI  - Integrin alpha v beta 8. Interaction with vitronectin and functional divergence
      of the beta 8 cytoplasmic domain.
AB  - The integrin beta 8 subunit was identified by cloning and sequencing of the cDNA
      and has been shown to associate with the alpha v subunit (Moyle, M., Napier, M.
      A., and McLean, J. W. (1991) J. Biol. Chem. 266, 19650-19658). We now present
      initial data on its functional properties. We produced a recombinant secreted
      form of alpha v beta 8 and used it to raise monoclonal antibodies that recognize
      the alpha v beta 8 complex or the beta 8 subunit alone on the surface of melanoma
      cells and on beta 8-transfected human embryonic kidney (293) cells. Affinity
      chromatography experiments showed that secreted alpha v beta 8 bound to
      vitronectin but not to fibronectin, collagen, or fibrinogen. Supporting evidence
      that intact full-length alpha v beta 8 could also bind to vitronectin-Sepharose
      was provided by performing affinity chromatography with the melanoma cell line
      MeWo, which normally expresses the intact beta 8 subunit. By studying the
      adhesive properties of melanoma cells and beta 8-transfected 293 cells, we found
      that alpha v beta 8 by itself does not promote cell adhesion on a vitronectin
      coated substrate. To test the respective functional activities of the beta 8
      extracellular and cytoplasmic domains, we analyzed chimeric beta 8/beta 3 subunit
      constructs. The beta 3 subunit was chosen because full-length beta 3, when
      transfected into 293 cells, strongly supports cell adhesion. We found that a
      chimeric integrin containing the beta 3 extracellular domain combined with the
      beta 8 transmembrane and cytoplasmic domains did not promote 293 cell adhesion.
      Conversely, a chimeric integrin construct combining the beta 8 extracellular
      domain with the beta 3 transmembrane and cytoplasmic domains did promote adhesion
      of transfected 293 cells. This suggests that the beta 8 cytoplasmic domain does
      not interact with the cytoskeleton and with cytoplasmic signaling pathways in an
      adhesion-promoting fashion. We conclude that the beta 8 cytoplasmic domain, which
      is structurally unrelated to the conserved cytoplasmic domains of other beta
      subunits, is functionally distinct.

PMID- 7525579
TI  - Human mitochondrial transcription termination exhibits RNA polymerase
      independence and biased bipolarity in vitro.
AB  - Human mitochondrial 16 S rRNA 3'-end formation requires a tridecamer template
      sequence and a trans-acting protein of approximately 34 kDa. This protein binds
      tightly to its target sequence and further analysis of the protein-DNA complex
      revealed that the DNA is bent. Either T3, T7, Escherichia coli, or yeast
      mitochondrial RNA polymerase produced transcripts mapping at this termination
      site. With these heterologous RNA polymerase, RNA 3'-end formation was detected
      only in the transcription polarity opposite that of mitochondrial rRNA synthesis;
      the efficiency of termination in the homologous human RNA polymerase system is
      approximately 2-fold greater in this same opposite polarity. These results
      suggested the possible importance of biased bipolar transcription termination in
      vivo. For wild-type mtDNA, the apparent relative efficiency of termination in
      vivo reflected the values determined in vitro. Examination of a pathogenic human
      mtDNA mutation known to result in impaired termination in vitro showed no
      significant differences in relative transcript abundances in vivo, despite a loss
      of in vitro termination efficiency in both directions. Recently, six additional
      mitochondrial disease-associated point mutations have been reported that cluster
      at the human mitochondrial transcription termination site. None of these resulted
      in significantly impaired transcription termination in vitro.

PMID- 7525580
TI  - Inhibition of E-selectin gene transcription through a cAMP-dependent protein
      kinase pathway.
AB  - Cytokines induce the expression of E-selectin, VCAM-1, and ICAM-1 on human
      umbilical vein endothelial cells (HUVECs). We show that expression of these
      surface proteins is differently affected by cAMP. Increased cAMP levels decrease
      E-selectin and VCAM-1 but increase ICAM-1 expression. We demonstrate by mRNA half
      life analysis and nuclear run-on assays that the cAMP repression of E-selectin
      occurs at the transcription level. This effect is abolished by protein kinase A
      inhibition, suggesting that repression is mediated by protein kinase A-driven
      phosphorylation. We found that a minimal E-selectin promoter sequence necessary
      to confer cytokine inducibility is also sufficient to mimic the cAMP effect in
      transfected HUVECs. Previously we characterized two regions (NF-kappa B and NF
      ELAM1) of the minimal promoter that bind transcription factors necessary for E
      selectin induction, Increased cAMP did not alter the binding of the complexes
      formed on either the NF-kappa B or NF-ELAM1 site. In contrast, in interleukin-1
      treated HUVECs transactivity due to an NF-kappa B site is reduced by elevated
      cAMP. Increased cAMP in HUVECs appears to induce a protein kinase activity that
      reduces the cytokine signal for E-selectin and VCAM-1 expression. The reduction
      in signal may occur through an inhibitory phosphorylation of one or more of the
      factors responsible for regulating E-selectin expression.

PMID- 7525581
TI  - Characterization of an antisense Inr element in the eIF-2 alpha gene.
AB  - We recently discovered an opposing initiator promoter (Inr) downstream of the
      sense promoter region of the eIF-2 alpha gene (Silverman, T., Noguchi, M., and
      Safer, B. (1992) J. Biol. Chem. 267, 9738-9742). By reverse
      transcriptase/polymerase chain reaction analysis of G0 and activated (G1) T
      lymphocyte RNAs, overlapping sense and antisense transcripts are now identified.
      Sense transcription of the eIF-2 alpha gene proceeds from left to right to
      generate alpha-mRNA; antisense transcription proceeds from right to left to
      generate RNA, having a sequence complementary to eIF-2 alpha mRNA. Upstream
      indicates a position 5' relative to the transcription start site. Using DNase I
      footprint analysis and EMSA, we have found a potential cis-regulatory sequence
      immediately upstream of the Inr which binds a 43-kDa protein. In addition to
      conferring protection against DNase I (+457 to +474), the factor also generates
      hypersensitive sites directly over the Inr (+447 to +457). Insertion of the Inr
      footprint region into a luciferase reporter gene construct increases expression
      150-fold. While mutation of the Inr conserved sequence decreases luciferase
      activity by 50%, mutation of the 43-kDa factor binding site inhibits luciferase
      activity by 20%. Sense orientation of the Inr footprint region decreases activity
      by 80%. The 43-kDa Inr-associated binding protein may be involved in allowing
      access of RNA polymerase II transcription complexes ot the initiation site of
      this TATA-less gene. A model for the regulation of eIF-2 alpha expression
      involving the rapid degradation of dsRNA generated by the relative activities of
      the two overlapping and opposing promoters is proposed.

PMID- 7525582
TI  - Phosphorylation of the desmoplakin COOH terminus negatively regulates its
      interaction with keratin intermediate filament networks.
AB  - Desmoplakins (DPs) are the most abundant proteins in the innermost portion of the
      desmosomal plaque and have been proposed to play a role in the attachment of
      intermediate filaments (IF) to cell-cell contact sites. Our previous results
      suggest that the globular end domains of DP perform dual functions: first, to
      target DP to the desmosome via the NH2 terminus and second, to attach IF to the
      desmosomal plaque via the COOH terminus. When ectopically expressed in most
      cultured cells, the COOH terminus plus the rod domain (DP. delta N.SerC23)
      exhibits striking coalignment with keratin IF networks. However, in certain cell
      types (e.g. PtK2) or in cells treated with forskolin to activate protein kinase
      A, DP. delta N.SerC23 exhibits a diffuse cytoplasmic distribution. A variant
      molecule (DP. delta N.GlyC23) in which a serine located 23 amino acids from the
      COOH terminus is altered to a glycine, thereby disrupting a protein kinase A
      consensus phosphorylation site, co-localizes with keratin IF networks regardless
      of cell type or forskolin treatment. Analysis of the phosphopeptide maps of these
      DP variants and endogenous DP is consistent with the phosphorylation of the
      serine 23 residues from the COOH terminus. These results suggest that
      phosphorylation of a specific residue in the DP COOH terminus may negatively
      regulate its interaction with keratin IF networks.

PMID- 7525583
TI  - Regulation of p68 RNA helicase by calmodulin and protein kinase C.
AB  - Human p68 RNA helicase is a nuclear RNA-dependent ATPase that belongs to a family
      of putative helicases known as the DEAD box proteins. These proteins have been
      implicated in aspects of RNA function including translation initiation, splicing,
      and ribosome assembly in a variety of organisms ranging from Escherichia coli to
      humans. While members of this family are believed to function in the manipulation
      of RNA secondary structure, little is known about the regulation of these
      enzymes. By immunological methods and sequence comparison, we have found that p68
      possesses a region of sequence similarity to the conserved protein kinase C
      phosphorylation site and calmodulin binding domain (also known as the IQ domain)
      of the neural-specific proteins neuromodulin (GAP-43) and neurogranin (RC3). We
      report that p68 is phosphorylated by protein kinase C in vitro and binds
      calmodulin in a Ca(2+)-dependent manner. Both phosphorylation and calmodulin
      binding inhibited p68 ATPase activity, suggesting that the RNA unwinding activity
      of p68 may be regulated by dual Ca2+ signal transduction pathways through its IQ
      domain.

PMID- 7525584
TI  - Ion channel properties of the reconstituted chloroplast triose
      phosphate/phosphate translocator.
AB  - The chloroplast triose phosphate/phosphate translocator (cTPT) was isolated from
      envelope membranes or from transformed yeast cells and reconstituted into
      artificial membranes. Ionic currents mediated by the cTPT across these membranes
      were investigated by flux measurements and by the patch-clamp technique. The
      results of the flux measurements indicate that inorganic phosphate (Pi) at
      saturating concentrations on both sides of the membrane and chloride (Cl-) at all
      applied concentrations are transported by the cTPT at rates about 20-fold higher
      than those measured in intact chloroplasts. After reconstitution of the protein
      into giant liposomes, single channel currents mediated by the cTPT were resolved
      with the patch-clamp technique. The protein was shown to be a voltage-dependent
      anion channel with complex gating revealing sublevels with conductances of 12,
      54, 96, and 138 pS for Cl- and 6 pS and 18 pS for Pi, respectively. Recordings
      from patches compromising multiple channels show a synchronously appearing non
      linear current voltage (I/V) relationship in symmetrical buffers, and a different
      gating at positive and negative membrane potentials. This suggests that the cTPT
      is incorporated into the membrane in a unidirectional orientation. 3
      Phosphoglycerate, a high affinity substrate of the transporter protein, induced a
      reversible flickering of open channel, and the channel open probability was
      decreased 60%. It is concluded that, besides its normal counter-exchange mode,
      the cTPT can also work as a voltage-dependent anion selective channel.

PMID- 7525585
TI  - Evidence for two distinct 60-kilodalton substrates of the SRC tyrosine kinase.
AB  - A monoclonal antibody to a 60-kDa substrate of the insulin receptor tyrosine
      kinase is utilized in the present studies to examine this molecule in 3T3 cells
      expressing either the transforming chicken c-Src (mutant Phe-527), the wild type
      molecule, or the parental cells. The tyrosine phosphorylation of this 60-kDa
      protein was greatly increased in cells expressing transforming Src and partially
      increased in cells expressing wild type enzyme. This tyrosine phosphorylation
      correlated with an increased association with the GTPase-activating protein of
      p21ras (GAP). However, this 60-kDa protein did not react with antibodies to
      another 62-kDa tyrosine-phosphorylated protein previously isolated from Src
      transformed cells (Wong, G., Muller, O., Clark, R., Conroy, L., Moran, M. F.,
      Polakis, P., and McCormick, F. (1992) Cell 69, 551-558), although this latter
      antibody did react with a 62-kDa protein in anti-phosphotyrosine precipitates
      from cells expressing transforming c-Src but not the parental cells. These two
      proteins could also be distinguished by their subcellular location, the ability
      of the latter but not the former protein to bind RNA, and their migration in SDS
      gels. Moreover, the 62-kDa RNA-binding phosphoprotein could be almost completely
      depleted from cell lysates with poly(U)-Sepharose without affecting the amount of
      either the GAP-associated 60-kDa tyrosine-phosphorylated protein or the protein
      precipitated with the monoclonal antibody. When the two proteins were
      phosphorylated in vitro with purified c-Src, they were both found to bind
      directly to the amino-terminal SH2 domain of GAP, although the RNA-binding
      protein was found to have a weaker affinity. These results indicate that two
      distinct 60-kDa proteins are substrates for the Src tyrosine kinase, one which
      binds RNA and the other which constitutes the major GAP-associated 60-kDa
      phosphoprotein.

PMID- 7525586
TI  - Identification of a receptor candidate for the carboxyl-terminal cell binding
      domain of thrombospondins.
AB  - The carboxyl-terminal cell binding domain (CBD) of thrombospondin-1 (TS1)
      contains two cell attachment peptides, 4N1s (RFYVVMWK) and 7N3 (FIRVVMY-EGKK),
      which share the sequence VVM. These peptides, and more soluble derivatives have
      been radiolabeled with 125I and used in conjunction with a variety of membrane
      impermeant cross-linking reagents to identify and characterize receptor
      candidates on several cell types. All of the VVM containing peptides tested with
      five different cross-linking reagents specifically labeled a 52-kDa protein,
      which was also affinity labeled by the recombinant TS1 CBD. After cross-linking
      peptide to K562 cells to block the 52-kDa protein, both cell adhesion to and
      affinity labeling by VVM peptides were inhibited in a concentration-dependent
      manner. Peptide labeling, like cell adhesion, was partially inhibited by heparin
      and stimulated by EDTA. The 52-kDa protein did not appear to contain sulfated
      glycan chains and was trypsin sensitive. It was recovered in a membrane fraction
      and was readily solubilized with Triton X-100 and X-114. Upon phase separation of
      the Triton X-114, the 52-kDa protein partitioned into the hydrophobic detergent
      phase. The detergent-solubilized receptor candidate bound selectively to wheat
      germ agglutinin-Sepharose, and after cell surface labeling with a membrane
      impermeant biotinylating reagent, bound to streptavidin-Sepharose. Furthermore,
      fluorescent beads covalently derivatized with peptide specifically decorated
      intact K562 cells. Thus the properties of the 52-kDa protein are consistent with
      those of a receptor for the CBD of TS1 and other TS isoforms.

PMID- 7525587
TI  - The rat vault RNA gene contains a unique RNA polymerase III promoter composed of
      both external and internal elements that function synergistically.
AB  - A novel gene transcribed by RNA polymerase (pol) III has been recently identified
      that produces an RNA component of a large cytoplasmic ribonucleoprotein complex
      (Kickhoefer, V. A., Searles, R. P., Kedersha, N. L., Garber, M. E., Johnson, D.
      L., and Rome, L. H. (1993) J. Biol. Chem. 268, 7868-7873). Since sequence
      analysis revealed that this gene contains promoter elements from two different
      classes of RNA pol III gene promoters, we examined the function of the 5'
      flanking type-3 and internal type-2 sequences on transcription activity and the
      production of stable transcription complexes. We find that the vRNA gene contains
      a novel RNA pol III promoter, where both the external and internal sequences are
      essential for template activity and for the productive interaction of TFIIIC with
      the internal elements. Thus, the vRNA gene represents the first example of a
      template that requires both type-2 and type-3 promoter elements that appear to
      function synergistically in the formation of productive transcription complexes.
      We have further examined the function of the unique arrangement of an internal A
      box and two B box elements. We find that at least one B element is required for
      template activity. In the absence of the 5'-flanking sequence the presence of
      both B elements inhibits transcription and the binding of TFIIIC. The formation
      of active complexes is restored when either the B2 element is inactivated or the
      distance separating the two B elements is increased. Therefore, the B2 element
      appears to negatively regulate template activity in the absence of the upstream
      sequences. This unique RNA pol III promoter arrangement may provide a novel
      mechanism for the regulation of vRNA gene activity.

PMID- 7525588
TI  - Interaction of calmodulin with the cyclic GMP-gated channel of rod photoreceptor
      cells. Modulation of activity, affinity purification, and localization.
AB  - The cGMP-gated cation channel of rod photoreceptor cells plays a central role in
      the phototransduction process by controlling the influx of cations into the rod
      outer segment in response to changes in cGMP levels. Previous studies have shown
      that the cGMP-gated channel in native rod outer segment membrane vesicles is
      modulated by calmodulin in a calcium-dependent manner. In this study we report
      that the immunoaffinity-purified channel consisting of the 63-kDa alpha-subunit
      and a 240-kDa protein is also modulated by calmodulin when reconstituted into
      lipid vesicles. In the absence of calmodulin, the purified channel had an
      apparent Km of 33 microM and a Hill coefficient of 3.3 for cGMP-dependent efflux
      of Ca2+ from reconstituted lipid vesicles. In the presence of calmodulin, the Km
      increased to 44 microM without affecting the Hill coefficient or maximum velocity
      of ion efflux. Calmodulin modulation of the channel is inhibited by the
      calmodulin antagonist, mastoparan. In the absence of mastoparan, the half-maximum
      inhibition of channel activity (IC50) occurred at 1.85 +/- 0.25 nM calmodulin at
      a cGMP concentration of 12.5 microM; in the presence of mastoparan, the IC50
      value increased to 20.3 +/- 3.8 nM calmodulin. Based on the strong, selective
      interaction of calmodulin with the channel, an efficient, general method has been
      developed to isolate functionally active cGMP-gated channels from mammalian and
      amphibian photoreceptor membranes. Calmodulin extraction studies, Western
      blotting, and channel activity measurements indicate that endogenous rod outer
      segment calmodulin modulates the activity of the channel through its binding to
      the 240-kDa protein. From these studies we conclude that the 240-kDa protein of
      the cGMP-gated channel is a major calmodulin target protein of rod outer segment
      membranes.

PMID- 7525589
TI  - Epitope mapping for monoclonal antibodies identifies functional domains of
      pulmonary surfactant protein A that interact with lipids.
AB  - Pulmonary surfactant protein A (SP-A) contains 4 domains: a disulfide forming
      amino terminus, a collagen-like region, a neck region, and a carbohydrate
      recognition region. The protein binds the lipids dipalmitoylphosphatidylcholine
      and galactosylceramide and induces aggregation of phospholipid vesicles. SP-A
      also inhibits lipid secretion and enhances the uptake of phospholipid by alveolar
      type II cells. Previously described monoclonal antibody 1D6 blocks the inhibitory
      effect of SP-A on lipid secretion by type II cells, but antibody 6E3 has no
      effect. In the present study we mapped the epitopes for monoclonal antibodies 1D6
      and 6E3 by enzyme-linked immunoassay of recombinant proteins expressed using the
      baculovirus system, and investigated the domain that is responsible for the SP-A
      interactions with lipid. Monoclonal antibody 1D6 bound to mutant SP-As in which
      the neck portion of the molecule was deleted or substituted with that of mannose
      binding protein A, but 6E3 failed to bind to these mutants. In contrast, 1D6 did
      not bind to a chimera in which the carbohydrate recognition domain (CRD) was
      substituted with that of surfactant protein D (SP-D). In addition, 1D6 failed to
      recognize antigen in cells infected with the recombinant virus directing the
      synthesis of a Cys204-Cys218 (small disulfide loop) deletion within the CRD.
      Antibody 1D6 completely blocked the binding of SP-A to
      dipalmitoylphosphatidylcholine and galactosylceramide and liposome aggregation.
      By comparison, 6E3 failed to completely attenuate the interactions of SP-A with
      lipids. However, both 6E3 and 1D6 blocked the uptake of lipid by type II cells
      that is caused by SP-A. From these data, we conclude that: 1) the epitope for
      antibody 6E3 is located at the neck domain of SP-A and that for antibody 1D6 is
      at the small loop region in the CRD; 2) the CRD is essential for the SP-A
      functions of lipid binding, liposome aggregation, the inhibitory effect on lipid
      secretion, and the augmentation of lipid uptake by type II cells, and these
      activities are largely attributable to amino acid residues within the steric
      inhibitory footprint of 1D6 bound to the small disulfide loop region; and 3) the
      neck domain of SP-A may also be involved in the process of SP-A-mediated uptake
      of phospholipids by alveolar type II cells.

PMID- 7525590
TI  - Replantation, revascularization, and reconstruction of both legs after
      amputations. A case report.

PMID- 7525591
TI  - A proposal for deciding when to prophylactically administer bone marrow
      (granulocyte) stimulatory factors to patients receiving cytotoxic chemotherapy.

PMID- 7525592
TI  - A targeting model of boron neutron-capture therapy to hepatoma cells in vivo with
      a boronated anti-(alpha-fetoprotein) monoclonal antibody.
AB  - We described previously that 10B atoms delivered by monoclonal antibody (mAb)
      exerted a cytotoxic effect on AH66 cells in a dose-dependent manner upon thermal
      neutron irradiation in vitro. In the present study, the delivering capacity of
      boronated anti-(alpha-fetoprotein) (AFP) mAb to carry 10B atoms to AFP-producing
      tumor xenografts in nude mice was determined. Boronated mAb was prepared by
      conjugating 50 mM 10B compound to an anti-AFP mAb (2 mg/ml) using N-succinimidyl
      3-) (2-pyridyldithio) propionate. The number of 10B atoms conjugated directly to
      the mAb was estimated to be 459/antibody by prompt gamma-ray spectrometry. Boron
      concentrations in tumor tissue obtained 12, 24, 72, and 120 h after injection of
      3.0 mg 10B-conjugated anti-AFP mAb were 11.10 +/- 3.12 (SD, n = 6). 29.30 +/-
      5.11, 33.02 +/- 11.8, and 12.91 +/- 5.62 ppm respectively. For control 10B
      conjugated anti-dinitrophenol (DNP) mAb, the values were 9.59 +/- 0.99, 10.37 +/-
      2.86, 10.00 +/- 2.95, and 8.83 +/- 4.71 ppm respectively. The concentrations in
      blood were less than 0.40 +/- 0.10 ppm with anti-AFP mAb and less than 0.51 +/-
      0.15 ppm with anti-DNP mAb at each sampling time (12, 24, 72, and 120 h). The
      number of 10B atoms delivered to the tumor cells was calculated to be 0.62 x
      10(9), 1.63 x 10(9), 1.84 x 10(9) and 0.72 x 10(9) at each sampling time after
      injection of 10B-anti-AFP mAb. The amount of 10B atoms necessary for effective
      boron neutron-capture therapy was estimated to be 10(9)/tumor cell. We were able
      to carry 1.84 x 10(9) 10B atoms to AH66 tumor cells by using 10B-anti-AFP mAb.
      The accumulation reached its peak 72 h after injection. These data indicated that
      the 10B-conjugated antitumor mAb could deliver a sufficient amount of 10B atoms
      to the tumor cells to induce cytotoxic effects 72 h after injection upon thermal
      neutron irradiation.

PMID- 7525593
TI  - T lymphocytes, CD68-positive cells and vascularisation in thyroid carcinomas.
AB  - Immunohistochemical detection and quantification of CD3- and CD45RO-positive
      lymphocytes and CD68-positive cells in 75 thyroid carcinomas of follicular cell
      origin revealed rising levels for these parameters associated with
      dedifferentiation. A parallel trend towards reduction of vascularisation,
      determined as CD31-positive blood vessels, with decreasing differentiation became
      evident, statistically only significant when well-differentiated follicular and
      anaplastic carcinomas were compared. Positive correlations could be demonstrated
      between the density of CD68-, CD3-, and CD45RO-positive cells as well as between
      the density of CD68-, and CD3-, and CD45RO-positive cells and vascularisation.
      These correlations were expected, as the interaction of CD68-positive cells and T
      lymphocytes results in the production of angiogenesis factors, ultimately leading
      to better vascularisation of the tumour. Nevertheless, the tumour cells
      themselves are variously capable of producing angiogenic substances. The obvious
      lack of positive correlation between the density of tumour-infiltrating cells
      determined in this study and vascularisation, despite reduced vascularisation in
      less differentiated tumours that contained increasing numbers of tumour
      infiltrating cells, seems to be due to functional heterogeneity of
      morphologically similar tumours.

PMID- 7525594
TI  - Pineal parenchymal tumors: cell differentiation and prognosis.
AB  - Eleven pineal parenchymal tumors were studied using various antibodies specific
      to the central nervous system and cell-proliferation-related antigen MIB-1 in
      order to examine the divergent types of cell differentiation and also evaluate
      prognosis. Electron microscopy was also performed. All tumors were
      immunohistochemically positive to chromogranin A and alpha B crystallin, and were
      also highly positive to retinal S protein. Pineocytoma cells contained
      microtubules, intermediate filaments, glial bundles, clear-centered vesicles and
      synaptic apparati. Pineoblastoma cells also had microtubules and neurofilaments,
      but glial filaments and definite synapses were not identifiable. Pineal
      parenchymal tumors were considered to be of pinealocyte origin, and there was a
      continuous spectrum of divergent cell differentiation between pineocytoma and
      pineoblastoma cells. The MIB-1 labeling index correlated well with histological
      malignancy, neuronal differentiation evaluated immunohistochemically by both
      neurofilament protein and synaptophysin, and cases with seeding potentials.
      Although histopathological features of neuronal development were, until recently,
      seen as the hallmark of benign prognosis in pineal parenchymal tumors, they are
      now thought to be only one of the pieces of evidence that may be used for
      purposes of prognosis.

PMID- 7525595
TI  - The amino-terminal region of the retinoblastoma gene product binds a novel
      nuclear matrix protein that co-localizes to centers for RNA processing.
AB  - The tumor suppressing capacity of the retinoblastoma protein (p110RB) is
      dependent on interactions made with cellular proteins through its carboxy
      terminal domains. How the p110RB amino-terminal region contributes to this
      activity is unclear, though evidence now indicates it is important for both
      growth suppression and regulation of the full-length protein. We have used the
      yeast two-hybrid system to screen for cellular proteins which bind to the first
      300 amino acids of p110RB. The only gene isolated from this screen encodes a
      novel 84-kD nuclear matrix protein that localizes to subnuclear regions
      associated with RNA processing. This protein, p84, requires a structurally
      defined domain in the amino terminus of p110RB for binding. Furthermore, both in
      vivo and in vitro experiments demonstrate that p84 binds preferentially to the
      functionally active, hypophosphorylated form of p110RB. Thus, the amino terminus
      of p110RB may function in part to facilitate the binding of growth promoting
      factors at subnuclear regions actively involved in RNA metabolism.

PMID- 7525597
TI  - Degeneration of neural cells in the central nervous system of mice deficient in
      the gene for the adhesion molecule on Glia, the beta 2 subunit of murine Na,K
      ATPase.
AB  - We generated mice, null mutant in the adhesion molecule on glia (AMOG), the beta
      2 subunit of the murine Na,K-ATPase gene. These mice exhibit motor incoordination
      at 15 d of age, subsequently tremor and paralysis of extremities, and die at 17
      18 d after birth. At these ages, the mutants have enlarged ventricles,
      degenerating photoreceptor cells, and swelling and degeneration of astrocytic
      endfeet, leading to vacuoles adjoining capillaries of brain stem, thalamus,
      striatum, and spinal cord. In tissue homogenates from entire brains of 16-17-d
      old mutants, Na,K-ATPase activity and expression of the beta 1 subunit of the
      Na,K-ATPase and of the neural adhesion molecules L1, N-CAM, and MAG appear
      normal. We suggest that the mutant phenotype can be related primarily to reduced
      pump activity, with neural degeneration as a possible consequence of osmotic
      imbalance.

PMID- 7525596
TI  - A novel FK506- and rapamycin-binding protein (FPR3 gene product) in the yeast
      Saccharomyces cerevisiae is a proline rotamase localized to the nucleolus.
AB  - The gene (FPR3) encoding a novel type of peptidylpropyl-cis-trans-isomerase
      (PPIase) was isolated during a search for previously unidentified nuclear
      proteins in Saccharomyces cerevisiae. PPIases are thought to act in conjunction
      with protein chaperones because they accelerate the rate of conformational
      interconversions around proline residues in polypeptides. The FPR3 gene product
      (Fpr3) is 413 amino acids long. The 111 COOH-terminal residues of Fpr3 share
      greater than 40% amino acid identity with a particular class of PPIases, termed
      FK506-binding proteins (FKBPs) because they are the intracellular receptors for
      two immunosuppressive compounds, rapamycin and FK506. When expressed in and
      purified from Escherichia coli, both full-length Fpr3 and its isolated COOH
      terminal domain exhibit readily detectable PPIase activity. Both fpr3 delta null
      mutants and cells expressing FPR3 from its own promoter on a multicopy plasmid
      have no discernible growth phenotype and do not display any alteration in
      sensitivity to the growth-inhibitory effects of either FK506 or rapamycin. In S.
      cerevisiae, the gene for a 112-residue cytosolic FKBP (FPR1) and the gene for a
      135-residue ER-associated FKBP (FPR2) have been described before. Even fpr1 fpr2
      fpr3 triple mutants are viable. However, in cells carrying an fpr1 delta mutation
      (which confers resistance to rapamycin), overexpression from the GAL1 promoter of
      the C-terminal domain of Fpr3, but not full-length Fpr3, restored sensitivity to
      rapamycin. Conversely, overproduction from the GAL1 promoter of full-length Fpr3,
      but not its COOH-terminal domain, is growth inhibitory in both normal cells and
      fpr1 delta mutants. In fpr1 delta cells, the toxic effect of Fpr3 overproduction
      can be reversed by rapamycin. Overproduction of the NH2-terminal domain of Fpr3
      is also growth inhibitory in normal cells and fpr1 delta mutants, but this
      toxicity is not ameliorated in fpr1 delta cells by rapamycin. The NH2-terminal
      domain of Fpr3 contains long stretches of acidic residues alternating with blocks
      of basic residues, a structure that resembles sequences found in nucleolar
      proteins, including S. cerevisiae NSR1 and mammalian nucleolin. Indirect
      immunofluorescence with polyclonal antibodies raised against either the NH2- or
      the COOH-terminal segments of Fpr3 expressed in E. coli demonstrated that Fpr3 is
      located exclusively in the nucleolus.

PMID- 7525598
TI  - Receptor tyrosine kinase signaling required for integrin alpha v beta 5-directed
      cell motility but not adhesion on vitronectin.
AB  - FG human pancreatic carcinoma cells adhere to vitronectin using integrin alpha v
      beta 5 yet are unable to migrate on this ligand whereas they readily migrate on
      collagen in an alpha 2 beta 1-dependent manner. We report here that epidermal
      growth factor receptor (EGFR) activation leads to de novo alpha v beta 5
      dependent FG cell migration on vitronectin. The EGFR specific tyrosine kinase
      inhibitor tyrphostin 25 selectively prevents EGFR autophosphorylation thereby
      preventing the EGF-induced FG cell migration response on vitronectin without
      affecting constitutive migration on collagen. Protein kinase C (PKC) activation
      also leads to alpha v beta 5-directed motility on vitronectin; however, this is
      not blocked by tyrosine kinase inhibitors. In this case, PKC activation appears
      to be associated with and downstream of EGFR signaling since calphostin C, an
      inhibitor of PKC, blocks FG cell migration on vitronectin induced by either PKC
      or EGF. These findings represent the first report implicating a receptor tyrosine
      kinase in a specific integrin mediated cell motility event independent of
      adhesion.

PMID- 7525600
TI  - Characterization of the KLP68D kinesin-like protein in Drosophila: possible roles
      in axonal transport.
AB  - This paper describes the molecular and biochemical properties of KLP68D, a new
      kinesin-like motor protein in Drosophila melanogaster. Sequence analysis of a
      full-length cDNA encoding KLP68D demonstrates that this protein has a domain that
      shares significant sequence identity with the entire 340-amin acid kinesin heavy
      chain motor domain. Sequences extending beyond the motor domain predict a region
      of alpha-helical coiled-coil followed by a globular "tail" region; there is
      significant sequence similarity between the alpha-helical coiled-coil region of
      the KLP68D protein and similar regions of the KIF3 protein of mouse and the KRP85
      protein of sea urchin. This finding suggests that all three proteins may be
      members of the same family, and that they all perform related functions. KLP68D
      protein produced in Escherichia coli is, like kinesin itself, a plus-end directed
      microtubule motor. In situ hybridization analysis of KLP68D RNA in Drosophila
      embryos indicates that the KLP68D gene is expressed primarily in the central
      nervous system and in a subset of the peripheral nervous system during
      embryogenesis. Thus, KLP68D may be used for anterograde axonal transport and
      could conceivably move cargoes in fly neurons different than those moved by
      kinesin heavy chain or other plus-end directed motors.

PMID- 7525601
TI  - Making a connection: direct binding between keratin intermediate filaments and
      desmosomal proteins.
AB  - In epidermal cells, keratin intermediate filaments connect with desmosomes to
      form extensive cadherin-mediated cytoskeletal architectures. Desmoplakin (DPI), a
      desmosomal component lacking a transmembrane domain, has been implicated in this
      interaction, although most studies have been conducted with cells that contain
      few or no desmosomes, and efforts to demonstrate direct interactions between
      desmoplakin and intermediate filaments have not been successful. In this report,
      we explore the biochemical nature of the connections between keratin filaments
      and desmosomes in epidermal keratinocytes. We show that the carboxy terminal
      "tail" of DPI associates directly with the amino terminal "head" of type II
      epidermal keratins, including K1, K2, K5, and K6. We have engineered and purified
      recombinant K5 head and DPI tail, and we demonstrate direct interaction in vitro
      by solution-binding assays and by ligand blot assays. This marked association is
      not seen with simple epithelial type II keratins, vimentin, or with type I
      keratins, providing a possible explanation for the greater stability of the
      epidermal keratin filament architecture over that of other cell types. We have
      identified an 18-amino acid residue stretch in the K5 head that is conserved only
      among type II epidermal keratins and that appears to play some role in DPI tail
      binding. This finding might have important implications for understanding a
      recent point mutation found within this binding site in a family with a
      blistering skin disorder.

PMID- 7525602
TI  - E1a induces the expression of epithelial characteristics.
AB  - Cells closely resembling epithelia constitute the first specific cell type in a
      mammalian embryo. Many other cell types emerge via epithelial-mesenchymal
      differentiation. The transcription factors and signal transduction pathways
      involved in this differentiation are being elucidated. I have previously reported
      (Frisch, 1991) that adenovirus E1a is a tumor suppressor gene in certain human
      cell lines. In the present report, I demonstrate that E1a expression caused
      diverse human tumor cells (rhabdomyosarcoma, fibrosarcoma, melanoma,
      osteosarcoma) and fibroblasts to assume at least two of the following epithelial
      characteristics: (a) epithelioid morphology; (b) epithelial-type intercellular
      adhesion proteins localized to newly formed junctional complexes; (c) keratin
      containing intermediate filaments; and (d) down-regulation of non-epithelial
      genes. E1a thus appeared to partially convert diverse human tumor cells into an
      epithelial phenotype. This provides a new system for molecular analysis of
      epithelial-mesenchymal interconversions. This effect may also contribute to E1a's
      tumor suppression activity, possibly through sensitization to anoikis (Frisch,
      S.M., and H. Francis, 1994. J. Cell Biol. 124:619-626).

PMID- 7525599
TI  - ICAM-3 regulates lymphocyte morphology and integrin-mediated T cell interaction
      with endothelial cell and extracellular matrix ligands.
AB  - Leukocyte activation is a complex process that involves multiple cross-regulated
      cell adhesion events. In this report, we investigated the role of intercellular
      adhesion molecule-3 (ICAM-3), the third identified ligand for the beta 2 integrin
      leukocyte function-associated antigen-1 (LFA-1), in the regulation of leukocyte
      adhesion to ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and the 38- and
      80-kD fragments of fibronectin (FN40 and FN80). The activating anti-ICAM-3
      HP2/19, but not other anti-ICAM-3 mAb, was able to enhance T lymphoblast adhesion
      to these proteins when combined with very low doses of anti-CD3 mAb, which were
      unable by themselves to induce this phenomenon. In contrast, anti-ICAM-1 mAb did
      not enhance T cell attachment to these substrata. T cell adhesion to ICAM-1, VCAM
      1, FN40, and FN80 was specifically blocked by anti-LFA-1, anti-VLA alpha 4, and
      anti-VLA alpha 5 mAb, respectively. The activating anti-ICAM-3 HP2/19 was also
      able to specifically enhance the VLA-4- and VLA-5-mediated binding of leukemic T
      Jurkat cells to VCAM-1, FN40, and FN80, even in the absence of cooccupancy of the
      CD3-TcR complex. We also studied the localization of ICAM-3, LFA-1, and the VLA
      beta 1 integrin, by immunofluorescence microscopy, on cells interacting with ICAM
      1, VCAM-1 and FN80. We found that the anti-ICAM-3 HP2/19 mAb specifically
      promoted a dramatic change on the morphology of T lymphoblasts when these cells
      were allowed to interact with those adhesion ligands. Under these conditions, it
      was observed that a large cell contact area from which an uropod-like structure
      (heading uropod) was projected toward the outer milieu. However, when T blasts
      were stimulated with other adhesion promoting agents as the activating anti-VLA
      beta 1 TS2/16 mAb or phorbol esters, this structure was not detected. The anti
      ICAM-3 TP1/24 mAb was also unable to induce this phenomenon. Notably, a striking
      cell redistribution of ICAM-3 was induced specifically by the HP2/19 mAb, but not
      by the other anti-ICAM-3 mAb or the other adhesion promoting agents. Thus, ICAM-3
      was almost exclusively concentrated in the most distal portion of the heading
      uropod whereas either LFA-1 or the VLA beta 1 integrin were uniformly distributed
      all over the large contact area. Moreover, this phenomenon was also observed when
      T cells were specifically stimulated with the HP2/19 mAb to interact with TNF
      alpha-activated endothelial cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525604
TI  - Complement receptor 3 (CR3, Mac-1, integrin alpha M beta 2, CD11b/CD18) is
      required for tyrosine phosphorylation of paxillin in adherent and nonadherent
      neutrophils.
AB  - Expression of the leukocyte (beta 2) integrins is required for many functions of
      activated neutrophils (PMN), even when there is no recognized ligand for any beta
      2 integrin. To investigate the hypothesis that beta 2 integrins may be involved
      in a signal transduction pathway related to cytoskeletal reorganization, we
      examined whether beta 2 integrins have a role in tyrosine phosphorylation of the
      cytoskeletal protein paxillin. Treatment of PMN in suspension with phorbol
      esters, f-Met-Leu-Phe, and TNF-alpha resulted in paxillin tyrosine
      phosphorylation. However, treatment of beta 2-deficient (LAD) PMN failed to
      induce paxillin tyrosine phosphorylation. Normal PMN phosphorylated paxillin in
      response to adhesion to immune complexes, while the LAD PMN did not. Adhesion of
      phorbol ester activated-LAD PMN to the extracellular matrix proteins fibronectin,
      laminin, and vitronectin failed to induce paxillin tyrosine phosphorylation.
      Treatment of activated normal PMN with mAb directed against the beta 2 integrin
      alpha chains demonstrated that CR3 (alpha M beta 2) was required for paxillin
      phosphorylation. Transfection of the cell line K562 with CR3 confirmed that CR3
      ligation resulted in paxillin tyrosine phosphorylation. As a control, K562
      transfected with CR2 (CD21) which bound equally avidly to the same complement C3
      derived ligand (C3bi) as the CR3 transfectants, showed no enhanced tyrosine
      phosphorylation of paxillin upon receptor ligation. While both CR2 and CR3
      transfectants showed efficient adhesion to a C3bi-coated surface, only the CR3
      transfectants spread during adhesion and phosphorylated paxillin. Together these
      data demonstrate that CR3 is required for paxillin phosphorylation during
      activation of both adherent and nonadherent PMN. Even PMN activated in suspension
      or by adhesion to immune complexes, when no CR3 ligand is apparent, still require
      CR3 for a signal transduction pathway leading to paxillin tyrosine
      phosphorylation. This pathway is likely to be important for PMN function in
      inflammation and host defense.

PMID- 7525603
TI  - Integrin alpha v beta 3 differentially regulates adhesive and phagocytic
      functions of the fibronectin receptor alpha 5 beta 1.
AB  - The plasma protein fibronectin is an important opsonin in wound repair and host
      defense. To better understand the process of fibronectin-mediated phagocytosis,
      we have transfected K562 cells, which endogenously express alpha 5 beta 1, with
      alpha v beta 3. In these transfectants, antibodies to alpha v beta 3 block
      phagocytosis of fibronectin-opsonized beads completely, even though half the
      ingestion occurs through endogenous alpha 5 beta 1 receptors. alpha 5 beta 1
      mediated adhesion to fibronectin-coated surfaces is unaffected by alpha v beta 3
      ligation. Neither alpha v beta 5 nor alpha M beta 2 ligation affects alpha 5 beta
      1 phagocytic function in transfectants expressing these receptors. Pharmacologic
      data suggest that alpha v beta 3 ligation suppresses the phagocytic competence of
      high affinity alpha 5 beta 1 receptors through a signal transduction pathway,
      perhaps involving protein kinase C. In addition to its significance for
      phagocytosis, alpha v beta 3 regulation of alpha 5 beta 1 function may be
      significant for its roles in cell migration, metastasis, and angiogenesis.

PMID- 7525605
TI  - Ca2+ release from subplasmalemmal stores as a primary event during exocytosis in
      Paramecium cells.
AB  - A correlated electrophysiological and light microscopic evaluation of trichocyst
      exocytosis was carried out the Paramecium cells which possess extensive cortical
      Ca stores with footlike links to the plasmalemma. We used not only intra- but
      also extracellular recordings to account for polar arrangement of ion channels
      (while trichocysts can be released from all over the cell surface). With three
      widely different secretagogues, aminoethyldextran (AED), veratridine and
      caffeine, similar anterior Nain and posterior Kout currents (both known to be
      Ca(2+)-dependent) were observed. Direct de- or hyperpolarization induced by
      current injection failed to trigger exocytosis. For both, exocytotic membrane
      fusion and secretagogue-induced membrane currents, sensitivity to or availability
      of Ca2+ appears to be different. Current responses to AED were blocked by W7 or
      trifluoperazine, while exocytosis remained unaffected. Reducing [Ca2+]o to < or =
      0.16 microM (i.e., resting [Ca2+]i) suppressed electrical membrane responses
      triggered with AED, while we had previously documented normal exocytotic membrane
      fusion. From this we conclude that the primary effect of AED (as of caffeine) is
      the mobilization of Ca2+ from the subplasmalemmal pools which not only activates
      exocytosis (abolished by iontophoretic EGTA injection) but secondarily also
      spatially segregated plasmalemmal Ca(2+)-dependent ion channels (indicative of
      subplasmalemmal [Ca2+]i increase, but irrelevant for Ca2+ mobilization). The
      45Ca2+ influx previously observed during AED triggering may serve to refill
      depleted stores. Apart from the insensitivity of our system to depolarization,
      the mode of direct Ca2+ mobilization from stores by mechanical coupling to the
      cell membrane (without previous Ca(2+)-influx from outside) closely resembles the
      model currently discussed for skeletal muscle triads.

PMID- 7525606
TI  - Filipin-sensitive caveolae-mediated transport in endothelium: reduced
      transcytosis, scavenger endocytosis, and capillary permeability of select
      macromolecules.
AB  - Caveolae or noncoated plasmalemmal vesicles found in a variety of cells have been
      implicated in a number of important cellular functions including endocytosis,
      transcytosis, and potocytosis. Their function in transport across endothelium has
      been especially controversial, at least in part because there has not been any
      way to selectively inhibit this putative pathway. We now show that the ability of
      sterol binding agents such as filipin to disassemble endothelial noncoated but
      not coated plasmalemmal vesicles selectively inhibits caveolae-mediated
      intracellular and transcellular transport of select macromolecules in
      endothelium. Filipin significantly reduces the transcellular transport of insulin
      and albumin across cultured endothelial cell monolayers. Rat lung microvascular
      permeability to albumin in situ is significantly decreased after filipin
      perfusion. Conversely, paracellular transport of the small solute inulin is not
      inhibited in vitro or in situ. In addition, we show that caveolae mediate the
      scavenger endocytosis of conformationally modified albumins for delivery to
      endosomes and lysosomes for degradation. This intracellular transport is
      inhibited by filipin both in vitro and in situ. Other sterol binding agents
      including nystatin and digitonin also inhibit this degradative process.
      Conversely, the endocytosis and degradation of activated alpha 2-macroglobulin, a
      known ligand of the clathrin-dependent pathway, is not affected. Interestingly,
      filipin appears to inhibit insulin uptake by endothelium for transcytosis, a
      caveolae-mediated process, but not endocytosis for degradation, apparently
      mediated by the clathrin-coated pathway. Such selective inhibition of caveolae
      not only provides critical evidence for the role of caveolae in the intracellular
      and transcellular transport of select macromolecules in endothelium but also may
      be useful for distinguishing transport mediated by coated versus noncoated
      vesicles.

PMID- 7525607
TI  - Synaptic activity and connective tissue remodeling in denervated frog muscle.
AB  - Denervation of skeletal muscle results in dramatic remodeling of the cellular and
      molecular composition of the muscle connective tissue. This remodeling is
      concentrated in muscle near neuromuscular junctions and involves the accumulation
      of interstitial cells and several extracellular matrix molecules. Given the role
      of extracellular matrix in neurite outgrowth and synaptogenesis, we predict that
      this remodeling of the junctional connective tissue directly influences the
      regeneration of the neuromuscular junction. As one step toward understanding the
      role of this denervation-induced remodeling in synapse formation, we have begun
      to look for the signals that are involved in initiating the junctional
      accumulations of interstitial cells and matrix molecules. Here, the role of
      muscle inactivity as a signal was examined. The distributions of interstitial
      cells, fibronectin, and tenascin were determined in muscles inactivated by
      presynaptic blockade of muscle activity with tetrodotoxin. We found that blockade
      of muscle activity for up to 4 wk produced neither the junctional accumulation of
      interstitial cells nor the junctional concentrations of tenascin and fibronectin
      normally present in denervated frog muscle. In contrast, the muscle inactivity
      induced the extrajunctional appearance of two synapse-specific molecules, the
      acetylcholine receptor and a muscle fiber antigen, mAb 3B6. These results
      demonstrate that the remodeling of the junctional connective tissue in response
      to nerve injury is a unique response of muscle to denervation in that it is
      initiated by a mechanism that is independent of muscle activity. Thus connective
      tissue remodeling in denervated skeletal muscle may be induced by signals
      released from or associated with the nerve other than the evoked release of
      neurotransmitter.

PMID- 7525608
TI  - Beta 2 integrin-dependent tyrosine phosphorylation of paxillin in human
      neutrophils treated with tumor necrosis factor.
AB  - The focal adhesion protein paxillin undergoes tyrosine phosphorylation in
      response to signals mediated by integrins, neuropeptides and oncogene products,
      possibly via activation of the focal adhesion-associated kinase, p125FAK. In the
      present work, tumor necrosis factor-alpha (TNF) stimulated tyrosine
      phosphorylation of paxillin in human neutrophils. Cell adhesion and participation
      of the beta 2 integrin CD18 were necessary, but not sufficient, for the response.
      Adherent neutrophils also tyrosine phosphorylated paxillin in response to phorbol
      ester, formylmethionyl-leucyl-phenylalanine and opsonized bacteria. In contrast,
      p125FAK was constitutively tyrosine phosphorylated in a manner unaffected by
      adherence and/or TNF. Thus, cytokines and microbial products are among the
      stimuli that can induce the tyrosine phosphorylation of paxillin, and kinases
      other than p125FAK may be responsible. This is the first identification of
      paxillin and p125FAK in human cells and neutrophils, and one of the few
      identifications of a specific protein that undergoes tyrosine phosphorylation in
      response to any agonist in neutrophils or in response to TNF in any cell.

PMID- 7525609
TI  - Distinct cell surface ligands mediate T lymphocyte attachment and rolling on P
      and E selectin under physiological flow.
AB  - Memory T lymphocytes extravasate at sites of inflammation, but the mechanisms
      employed by these cells to initiate contact and tethering with endothelium are
      incompletely understood. An important part of leukocyte extravasation is the
      initiation of rolling adhesions on endothelial selectins; such events have been
      studied in monocytes and neutrophils but not lymphocytes. In this study, the
      potential of T lymphocytes to adhere and roll on endothelial selectins in vitro
      was investigated. We demonstrate that T cells can form tethers and rolling
      adhesions on P selectin and E selectin under physiologic flow conditions.
      Tethering and rolling on P selectin was independent of cell-surface cutaneous
      lymphocyte antigen (CLA) expression, which correlated strictly with the capacity
      of T cells to form rolling adhesions under flow on E selectin. T cell tethering
      to P selectin was abolished by selective removal of cell surface sialomucins by a
      P. haemolytica O-glycoprotease, while cutaneous lymphocyte antigen expression was
      unaffected. A sialomucin molecule identical or closely related to P selectin
      glycoprotein ligand-1 (PSGL-1), the major P selectin ligand on neutrophils and HL
      60 cells, appears to be a major T cell ligand for P selectin. P selectin
      glycoprotein ligand-1 does not appear to support T cell rolling on E selectin. In
      turn, E selectin ligands do not appear to be associated with sialomucins. These
      data demonstrate the presence of structurally distinct ligands for P or E
      selectins on T cells, provide evidence that both ligands can be coexpressed on a
      single T cell, and mediate tethering and rolling on the respective selectins in a
      mutually exclusive fashion.

PMID- 7525610
TI  - High resolution analysis of cell cycle-correlated vimentin expression in
      asynchronously grown, TPA-treated MPC-11 cells by the novel flow cytometric
      multiparameter BrdU-Hoechst/PI and immunolabeling technique.
AB  - High resolution, multiparameter analysis using the flow cytometric BrdU/Hoechst
      quenching technique has been applied to study cell cycle kinetics and vimentin
      expression in individual cells of asynchronously grown MPC-11 mouse plasmacytoma
      cell cultures treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) to induce
      in vitro differentiation. BrdU treatment up to 16 h in the absence or presence of
      TPA did not affect either cell cycle progression or the kinetics or quantity of
      vimentin expression. TPA-treated cells became arrested in G1 phase of the second
      cell cycle; however, this G1 phase arrest was transient only. In addition, G1
      phase cells located prior to a putative transition point at the beginning of TPA
      treatment were completely blocked in cell cycle progression. There is also
      evidence that cells located in G1 or G2/M phase at the beginning of TPA treatment
      finally expressed low levels of vimentin. On the contrary, cells located in S
      phase at TPA exposure showed high vimentin levels after treatment. The results
      presented here show that, with the flow cytometric BrdU/Hoechst quenching
      technique, one can correlate time-dependent protein expression at the single cell
      level in asynchronously grown cultures not only with the actual cell cycle state,
      but also with the history of cell replication.

PMID- 7525612
TI  - Ornithine decarboxylase gene expression is aberrantly regulated via the cAMP
      signal transduction pathway in malignant H-ras transformed cell lines.
AB  - We have tested the hypothesis that H-ras transformed cells contain alterations in
      signal pathways important in controlling the expression of ornithine
      decarboxylase (ODC), the highly regulated rate-limiting activity in the
      biosynthesis of polyamines. Mouse 10T1/2 fibroblasts and a series of 10T1/2 H-ras
      transformed cell lines were treated with stimulators of cAMP synthesis (forskolin
      and cholera toxin), a biologically stable analogue of cAMP (8-bromo-cAMP), and an
      inhibitor of cAMP degradation (3-isobutyl-1-methylxanthine). Elevations in ODC
      gene expression were noted in H-ras transformed cells that were not observed in
      parental 10T1/2 fibroblasts. The forskolin-mediated effects were not detected
      with 1,9-dideoxyforskolin, a compound structurally related to forskolin, which
      does not activate adenyl cyclase. The effects observed with cholera toxin were
      not detected when cells were treated with the purified subunits of this compound,
      indicating that the toxin-induced effects were cAMP-specific. Actinomycin D
      treatment prior to forskolin exposure reduced the elevation observed in ODC gene
      expression indicating the involvement of the transcriptional process.
      Furthermore, we observed that cycloheximide treatment of malignant but not benign
      H-ras transformed cells significantly elevated ODC message level. Treatment of
      malignant cells with both cycloheximide and forskolin together resulted in a
      further additive elevation in ODC message, but a similar treatment of benign
      tumor cells reduced the forskolin-mediated increase in ODC message. In addition,
      treatment of H-ras transformed cells with the tumor promoter, 12-O
      tetradecanoylphorbol-13-acetate (TPA) led to an elevation in ODC mRNA levels not
      observed in parental 10T1/2 fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525611
TI  - Early cellular events couple covalent binding of reactive metabolites to cell
      killing by nephrotoxic cysteine conjugates.
AB  - Addition of the nephrotoxic cysteine conjugate, S-(1,2-dichlorovinyl)-L-cysteine
      (DCVC), to the LLC-PK1 line of renal epithelial cells leads to covalent binding
      of reactive intermediates followed by thiol depletion, lipid peroxidation, and
      cell death (Chen et al., 1990, J. Biol. Chem., 265:21603-21611). The present
      study was designed to determine if increased intracellular free calcium might
      play a role in this pathway of DCVC-induced toxicity by comparing the temporal
      relationships among increased intracellular free calcium, lipid peroxidation, and
      cytotoxicity. Intracellular free calcium increased 1 hr after DCVC treatment,
      long before LDH release occurred. The elevation of intracellular free calcium and
      cytotoxicity was prevented by inhibiting DCVC metabolism with AOA. The cell
      permeable chelators, Quin-2AM and EGTA-AM, prevented the toxicity. Pretreatment
      of cells with a nontoxic concentration of ionomycin increased intracellular free
      calcium and potentiated DCVC-induced LDH release. However, the antioxidant, DPPD,
      which blocks lipid peroxidation and toxicity, did not affect the increase in
      intracellular free calcium, whereas buffering intracellular calcium with Quin-2AM
      or EGTA-AM blocked both lipid peroxidation and toxicity without preventing the
      depletion of nonprotein sulfhydryls by DCVC. Ruthenium red, an inhibitor of
      mitochondrial calcium uptake, also blocked cell death. We hypothesize that
      covalent binding of the reactive fragment from DCVC metabolism leads to
      deregulation of intracellular calcium homeostasis and elevation of intracellular
      free calcium. Increased intracellular free calcium may in turn be coupled to
      mitochondrial damage and the accumulation of endogenous oxidants which cause
      lipid peroxidation and cell death.

PMID- 7525613
TI  - Endothelin secretion is regulated by cyclic AMP and phosphatase 2A in endothelial
      cells.
AB  - Endothelin is a 21 amino acid peptide secreted by endothelial cells and is the
      most potent vasoconstrictor known. The present study examines regulatory
      mechanisms of endothelin secretion, focusing on the role of protein
      phosphorylation. Endothelin secretion was measured by radioimmunoassay in primary
      cultures of human umbilical vein endothelial cells. While treatment that raised
      cAMP levels reduced the basal endothelin secretion rate, agents that elevated
      cGMP had no effect. Downregulation or inhibition of protein kinase C resulted in
      decreased endothelin secretion, suggesting that protein kinase C regulates
      endothelin secretion in the opposite direction to cAMP dependent protein kinases.
      Okadaic acid, at concentrations that selectively inhibit protein phosphatases 2A,
      reduced the endothelin secretion and the effects of okadaic acid and db-cAMP were
      additive. Endothelin production was stimulated by fetal calf serum and by the
      protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7),
      but was inhibited by the calmodulin antagonist trifluoperazine. The present
      findings that regulators of cAMP-dependent protein kinases, protein kinase C,
      calmodulin, and protein phosphatase 2A all affect endothelin secretion suggest
      that endothelin secretion is controlled by phosphorylation/dephosphorylation of
      as yet unidentified regulatory proteins within the cell.

PMID- 7525616
TI  - Differential effects of cytotactin/tenascin fusion proteins on intracellular pH
      and cell morphology.
AB  - Cytotactin/tenascin is a multidomain extracellular matrix protein that inhibits
      both cell spreading and intracellular alkalinization. The protein has multiple
      different domains which are homologous to regions in epidermal growth factor,
      fibronectin, and fibrinogen. In previous studies, we produced nonoverlapping
      fusion proteins corresponding to these domains and examined their effects on cell
      attachment and spreading. Based on their ability either to promote or to inhibit
      cell attachment, two of these fusion proteins were shown to be adhesive and two
      were shown to be counteradhesive. To determine how the adhesive and
      counteradhesive activities of different cytotactin/tenascin domains alter
      intracellular pH (designated pHi), we have measured pHi, in NIH3T3 and U251MG
      cells in the presence of the cytotactin/tenascin fusion proteins and intact
      cytotactin/tenascin, as well as fibronectin. Cells incubated in the presence of
      intact cytotactin/tenascin or of the counteradhesive fusion proteins had a pHi
      lower than control cells. In contrast, the presence of the adhesive fusion
      proteins or of fibronectin caused cells to have higher pHi values than control
      cells. When two fragments were simultaneously presented, one of which alone
      increased pHi and the other of which alone decreased pHi, the predominant effect
      was that of lowered pHi. Incubation with an RGD-containing peptide derived from
      the cytotactin/tenascin sequence inhibited alkalinization promoted by the
      adhesive fragment containing the second through sixth fibronectin type III
      repeats that was known to bind to integrins. Incubation of the cells with
      heparinase I or III inhibited the intracellular alkalinization of cells plated in
      the presence of the other adhesive fusion protein containing the fibrinogen
      domain, suggesting that heparan sulfate proteoglycans were involved in these pHi
      changes. The activity of protein kinase C appeared to be important for the
      changes in pHi mediated by all of the proteins. The protein kinase C inhibitor
      Calphostin C blocked the rise in pHi elicited by the adhesive fusion proteins and
      by fibronectin. Moreover, activation of protein kinase C by the addition of
      phorbol esters increased the pHi in cells plated on cytotactin/tenascin or
      counteradhesive fusion proteins and reversed their effects. The results of this
      study support the hypothesis that cytotactin/tenascin can bind to multiple cell
      surface receptors and thereby elicit different physiological responses. Decreases
      in pHi are correlated with the phenomenon of counteradhesion whereas the ability
      to increase pHi is associated with cell attachment via at least two different
      types of cell surface receptors. The data raise the possibility that binding of
      cytotactin/tenascin may influence primary cellular processes such as migration
      and proliferation through the differential regulation of pHi.

PMID- 7525615
TI  - Uptake of biotin by human hepatoma cell line, Hep G2: a carrier-mediated process
      similar to that of normal liver.
AB  - Little is known about the cellular and molecular regulation of the uptake process
      of the water-soluble vitamin biotin into liver cells, the major site of biotin
      utilization and metabolism. Such studies are best done using a highly viable and
      homogeneous cellular system that allows examination of prolonged exposure to an
      agent(s) or a particular condition(s) on the uptake process. Isolated hepatocytes
      when maintained in primary culture lose their ability to transport biotin by the
      specialized carrier system. The aim of the present study was, therefore, to
      examine the mechanism(s) of biotin uptake by the cultured human-derived liver
      cells, Hep G2. Uptake of biotin by Hep G2 cells was appreciable and linear for up
      to 10 min of incubation. The uptake process was Na+ gradient-dependent as
      indicated by studies of Na+ replacement and pretreatment of cells with gramicidin
      and ouabain. Biotin uptake was also dependent on both incubation temperature and
      intracellular energy. Unlabeled biotin and the structural analogs with free
      carboxyl groups (thioctic acid, desthiobiotin) but not those with blocked
      carboxyl group (biocytin, biotin methyl ester, and thioctic amide) caused
      significant inhibition of 3H-biotin uptake at 37 degrees C but not 4 degrees C.
      Initial rate of biotin uptake was saturable as a function of concentration at 37
      degrees C but was lower and linear at 4 degrees C. Pretreatment of Hep G2 cells
      with sulfhydryl group inhibitors (e.g., p-chloromercuribenzene sulfonate) led to
      a significant inhibition in biotin uptake; this inhibition was effectively
      reversed by reducing agents (e.g., dithiothreitol). Biotin uptake was also
      inhibited by the membrane transport inhibitors probenecid (noncompetitively),
      DIDS and furosemide but not by amiloride. Pretreatment of Hep G2 cells with
      valinomycin did not alter biotin uptake. The stoichiometric ratio of biotin to
      Na+ uptake in Hep G2 cells was also determined and found to be 1:1. These
      findings demonstrate that biotin uptake by these cultured liver cells is mediated
      through a specialized carrier system that is dependent on Na(+)-gradient,
      temperature, and energy and transports the vitamin by an electroneutral process.
      These findings are similar to those seen with native liver tissue preparations
      and demonstrate the suitability of Hep G2 cells for in-depth investigations of
      the cellular and molecular regulation of biotin uptake by the liver.

PMID- 7525614
TI  - Insulin-like growth factor (IGF) binding to a murine mammary epithelial cell
      line.
AB  - The goal of this study was to relate insulin-like growth factor (IGF) binding
      with IGF-stimulated growth in a murine mammary epithelial (COMMA-D/MME) cell
      line. Affinity crosslinking with [125I]IGF-I showed major bands at 224,000 and
      148,000 Mr that were ablated by the inclusion of IGF-I or -II at 130 nM.
      Scatchard-transformed [125I]IGF-I binding data was best fit by a two-site model,
      with 24,000 sites possessing a Kd of 0.33 nM and 1,000 sites possessing a Kd of
      8.09 nM per cell. Competition analysis showed ED50 values for IGF-I, -II, and
      insulin to be 0.90 +/- 0.03, 7.15 +/- 4.27, and 335 +/- 104 nM, respectively.
      Affinity crosslinking of [125I]IGF-II showed three major bands of 230,000,
      148,000, and 61,000 to 58,000 Mr. Unlabeled IGF-II ablated all bands, while IGF-I
      and insulin ablated only the 148,000 Mr band. Competition analysis showed ED50
      values for unlabeled IGF-I and -II to be 0.10 +/- 0.01 and 5.31 +/- 2.04 nM,
      respectively. In spite of the receptor affinity differences, no significant
      difference was noted in IGF-I and -II in capacity to stimulate cell growth. These
      data indicate that COMMA-D/MME cells express IGF receptors and that both IGFs are
      mitogenic.

PMID- 7525618
TI  - Enhanced phosphoinositide metabolism in colorectal carcinoma cells derived from
      familial adenomatous polyposis patients.
AB  - The production of the second messenger molecules diacylglycerol and inositol
      1,4,5-trisphosphate is mediated by activated phosphatidylinositol-specific
      phospholipase C (PLC) enzymes. We report the enhancement of the phosphoinositide
      metabolism pathway in KMS-4 and KMS-8 cells, both of which are human colorectal
      carcinoma cell lines derived from familial adenomatous polyposis patients. In
      these cells, the cellular contents of diacylglycerol and inositol 1,4,5
      trisphosphate were constitutively increased and the PLC activity in vitro was
      significantly high, as compared with those in normal colon cells or in other
      sporadic colorectal carcinoma cells. Northern and Western analyses showed the
      high expression levels of both PLC-gamma 1 and PLC-delta 1 in KMS-4 and KMS-8
      cells. Moreover, we detected the enhancement of protein-tyrosine kinase activity
      and tyrosine phosphorylation of PLC-gamma 1 in these KMS cells. These results
      suggest the involvement of activated phosphoinositide signaling pathways in the
      colorectal tumorigenesis of familial adenomatous polyposis.

PMID- 7525619
TI  - Does transcription by RNA polymerase play a direct role in the initiation of
      replication?
AB  - RNA polymerases have been implicated in the initiation of replication in
      bacteria. The conflicting evidence for a role in initiation in eukaryotes is
      reviewed.

PMID- 7525617
TI  - Modulation of bovine microvascular endothelial cell proteolytic properties by
      inhibitors of angiogenesis.
AB  - A tightly controlled increase in extracellular proteolysis, restricted both in
      time and space, is an important component of the angiogenic process, while anti
      proteolysis is effective in inhibiting angiogenesis. By focussing on the
      plasminogen activator (PA)-plasmin system, the objective of the present studies
      was to assess whether previously described inhibitors of angiogenesis modify
      bovine microvascular endothelial cell proteolytic properties. We demonstrate that
      although synthetic angiostatic steroids (U-24067 and U-42129), heparin, suramin,
      interferon alpha-2a, and retinoic acid are all inhibitors of in vitro
      angiogenesis, each of these agents has distinct effects on the plasminogen
      dependent proteolytic system. Specifically, angiostatic steroids and interferon
      alpha-2a reduce urokinase-type PA (u-PA) and PA inhibitor-1 activity, while
      heparin and retinoic acid increase u-PA activity. Suramin reduces cell-associated
      u-PA activity and greatly increases PAI-1 production at doses which induce
      monolayer disruption. These findings demonstrate that a spectrum of alterations
      in extracellular proteolysis is associated with anti-angiogenesis, and that anti
      angiogenesis and anti-proteolysis are not necessarily correlated. A reduction in
      extracellular proteolysis would be expected to reduce invasion, whereas an
      increase in proteolysis might modulate the activity of inhibitory cytokines,
      which in turn could reduce endothelial cell proliferation and migration and
      inhibit angiogenesis. The spectrum of effects on different elements of the PA
      system observed in response to the agents assessed suggests that the role of
      modulations in extracellular proteolytic activity in anti-angiogenesis is likely
      to be varied and complex.

PMID- 7525620
TI  - Concentration of pp125 focal adhesion kinase (FAK) at the myotendinous junction.
AB  - Focal adhesion kinase is a recently characterized tyrosine kinase that is
      concentrated at focal contacts in cultured cells. It is thought to play an
      important role in the regulation of the integrin-based signal transduction
      mechanism involved in the assembly of this membrane specialization. In this
      study, we examined the immunocytochemical distribution of focal adhesion kinase
      in Xenopus skeletal muscle and its role in the formation of two sarcolemmal
      specializations, the myotendinous junction and the neuromuscular junction, using
      a monoclonal antibody (2A7) against this protein. Immunoprecipitation of Xenopus
      embryonic tissues with this antibody demonstrated a single band at a relative
      molecular mass of 116 kDa. A distinct concentration of immunolabeling for focal
      adhesion kinase was observed at the myotendinous junction of muscle fibers in
      vivo. At this site, the labeling for this protein is correlated with an
      accumulation of phosphotyrosine immunolabeling. Focal adhesion kinase was not
      concentrated at the neuromuscular junction in muscle cells either in vivo or in
      vitro. However, it was localized at spontaneously formed acetylcholine receptor
      clusters in cultured Xenopus myotomal muscle cells, although its distribution was
      not exactly congruent with that of the receptors. In these cells, the
      accumulation focal adhesion kinase was induced by polystyrene microbeads. In
      addition, beads also induce the formation of acetylcholine receptor clusters and
      myotendinous junction-like specializations. By following the appearance of the
      focal adhesion kinase relative to the formation of these sarcolemmal
      specializations at bead-muscle contacts in cultured muscle cells, we conclude
      that the accumulation of this protein was in pace with the development of the
      myotendinous junction, but occurred well after the clustering of acetylcholine
      receptors. These results suggest that focal adhesion kinase may be involved in
      the development and/or maintenance of the myotendinous junction through an
      integrin-based signaling system. Although it can accumulate at acetylcholine
      receptor clusters formed in culture, it does not appear to be involved in the
      development of the neuromuscular junction.

PMID- 7525621
TI  - Primary sequence of paxillin contains putative SH2 and SH3 domain binding motifs
      and multiple LIM domains: identification of a vinculin and pp125Fak-binding
      region.
AB  - Paxillin is a cytoskeletal protein involved in actin-membrane attachment at sites
      of cell adhesion to the extracellular matrix. Extensive tyrosine phosphorylation
      of this protein occurs during integrin-mediated cell adhesion, embryonic
      development, fibroblast transformation and following stimulation of cells by
      mitogens that operate through the family of seven membrane-spanning G-protein
      coupled receptors. Paxillin binds in vitro to the focal adhesion protein vinculin
      as well as to the SH3 domain of c-src and, when tyrosine phosphorylated, to the
      SH2 domain of v-crk. Here, we report the complementary DNA, and derived amino
      acid sequence, that codes for approximately 90% of the paxillin protein. We have
      identified a region in the amino-terminal half of the protein that supports the
      binding of both vinculin and the focal adhesion tyrosine kinase, pp125Fak.
      Although there is no significant overall homology with other identified proteins,
      the carboxyl third of paxillin contains one LIM domain and three LIM-like
      sequences. The LIM motif is common to a number of transcription factors and to
      two other focal adhesion proteins, zyxin and cysteine-rich protein. In addition
      to several potential tyrosine phosphorylation sites there are five tyrosine
      containing sequences that conform to SH2-binding motifs. The protein also
      contains a short proline-rich region indicative of a SH3-binding domain. Taken
      together, these data suggest that paxillin is a unique cytoskeletal protein
      capable of interaction with a variety of intracellular signalling, and
      structural, molecules important in growth control and the regulation of
      cytoskeletal organization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525622
TI  - Identification of dengue virus-infected cells in paraffin-embedded tissue using
      in situ polymerase chain reaction and DNA hybridization.
AB  - Using tissue from suckling mice infected with Dengue virus, the following
      improved method for detecting Dengue viral RNA in tissue sections was devised.
      Reverse transcription of the viral RNA to DNA was followed by the in situ
      polymerase chain reaction to amplify the viral nucleic acid. This was followed by
      DNA hybridization with an alkaline phosphatase-labelled probe. The enzyme was
      then reacted with Fast red and counterstained with hematoxylin. Viral nucleic
      acid was readily demonstrated within glial cells and macrophages in brains of
      animals infected with two different serotypes of Dengue.

PMID- 7525624
TI  - The effects of subcutaneous insulin-like growth factor-I infusion in insulin
      dependent diabetes mellitus.
AB  - Insulin-dependent diabetes can be associated with low insulin-like growth factor
      I (IGF-I) levels despite normal or even high GH secretion. The basis of the
      diabetic abnormalities in GH-IGF dynamics that contribute to insulin resistance
      and impaired fuel metabolism are not well understood. To further investigate
      these matters, this study evaluated baseline IGF system parameters and responses
      to recombinant human IGF-I in four diabetic adolescents and six pubertal stage
      matched controls. Spontaneous overnight and arginine-stimulated GH secretion,
      insulin, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were
      measured before, during, and after daily 10-h sc infusions of saline or IGF-I (20
      micrograms/kg.h). Baseline overnight GH secretion and IGFBP-1 and -3 levels were
      not significantly different in the two groups, but IGF-I levels were
      significantly lower and IGF-II levels were higher in diabetic subjects. IGF-I
      infusion produced a 3-fold increase in serum IGF-I levels and a reciprocal
      profound reduction in IGF-II levels in both groups. IGFBP-1 levels increased
      dramatically in diabetics and modestly in normal subjects in response to IGF-I
      infusion, but IGFBP-3 levels were not significantly altered. Spontaneous
      overnight and arginine-stimulated GH secretion were suppressed by about 50% in
      both groups after IGF-I infusion. Insulin requirements were substantially reduced
      in diabetics receiving IGF-I, and insulin secretion was suppressed in normal
      subjects, with no evidence of a change in insulin half-life. Blood glucose
      remained stable in both groups throughout saline and IGF-I infusions, and no
      hypoglycemia or other adverse effect occurred during IGF-I infusions. Further
      studies are necessary to determine whether the addition of IGF-I to insulin
      replacement therapy may stably reduce the insulin requirement, maintain normal GH
      levels, and perhaps achieve better metabolic and anabolic balance in the
      treatment of insulin-dependent diabetes.

PMID- 7525623
TI  - Quantitative micro P30 and reverse transcriptase assays for Moloney murine
      leukemia virus.
AB  - An anti-P30 immunohistochemical and a reverse transcriptase assay for Moloney
      murine leukemia virus (MoMLV) are adapted to 96-well plates. The assay results
      are shown to be directly proportional to the number of infectious particles, and
      can therefore be used to estimate the infective titers of a virus preparation.
      The micro P30 assay yields a direct estimate of infectious centers, and the
      reverse transcriptase assay quantitates progeny from a single cycle of
      replication. The semi-automated nature of these assays is well suited to the
      analysis of a large number of samples and therefore permits the examination of
      the efficiency of the process of retroviral/MoMLV infection under varied times or
      conditions.

PMID- 7525626
TI  - Pituitary size assessed with magnetic resonance imaging as a measure of growth
      hormone secretion in long term survivors of childhood cancer.
AB  - We investigated 37 long term survivors of childhood cancer to study the
      relationship among growth, GH secretion, and pituitary size. The median follow-up
      time after diagnosis was 13.2 yr. The pituitary gland was visualized with
      magnetic resonance imaging. Radiated patients (n = 25) had a reduced relative
      height and showed a greater reduction in relative height after diagnosis than
      nonradiated patients (n = 12). The patients had lower spontaneous nocturnal GH
      secretion than controls due to a reduced peak amplitude. Spontaneous GH secretion
      was lower in radiated patients than in nonradiated subjects. The patients had
      lower plasma insulin-like growth factor-I (IGF-I) and serum IGF-binding protein-3
      (IGFBP-3) concentrations than the controls. Radiated subjects had decreased IGF-I
      and IGFBP-3 concentrations compared to nonradiated subjects. Half of the patients
      (20 of 37) evaluated with magnetic resonance imaging had a reduced pituitary size
      (pituitary height, < -2 SD score). Radiated subjects had smaller pituitary glands
      than nonradiated ones. Seventeen of 20 patients (85%) with reduced pituitary size
      had decreased nocturnal GH release. There was a positive correlation between
      nocturnal GH secretion, plasma IGF-I, and serum IGFBP-3 levels, on the one hand,
      and pituitary height, on the other. These results indicate that cranial radiation
      may result in tissue damage, leading to decreased pituitary size, reduced
      spontaneous GH secretion, and impaired linear growth. The finding of reduced IGF
      I levels in both radiated and nonradiated patients combined with decreased IGFBP
      3 concentrations in radiated patients, indicates that cytotoxic chemotherapy may
      induce hepatic damage resulting in decreased IGF-I synthesis.

PMID- 7525627
TI  - Pituitary adenomas in childhood and adolescence.
AB  - A clinicopathological study of 56 pediatric patients with non-ACTH-secreting
      pituitary adenomas removed by a transsphenoidal neurosurgical approach was
      undertaken to better define the clinical presentation, to assess demographic
      factors, to determine the immunohistochemical staining characteristics of the
      tumors, and to evaluate the outcome of transsphenoidal surgical treatment and
      other adjuvant therapies. A separate analysis of prolactinoma patients was
      performed. All tumors were confirmed histologically and immunophenotyped for
      pituitary hormones. Forty-one patients had tumors that stained for PRL alone,
      eight patients had tumors that stained for PRL and GH, six patients had
      plurihormonal adenomas, and one patient had a tumor that stained for glycoprotein
      hormones. No tumors contained GH alone. Macroadenomas exceeded microadenomas
      (1.4:1). There were no male patients with microadenomas of any type. Females
      outnumbered males (3.3:1). Patients presented most frequently with headache,
      menstrual dysfunction (in females), galactorrhea, and hypopituitarism. All but
      one of the patients with hypopituitarism at presentation had macroadenomas. Tumor
      staining characteristics did not always correlate well with clinical status,
      especially with regard to GH-containing tumors. Pediatric pituitary tumors did
      not appear to be more invasive or more aggressive than adult pituitary tumors,
      contrary to some previous reports. The patients with microadenomas had a 70%
      operative cure rate and a 65% long term cure rate; the recurrence rate for
      microadenoma patients was 25%. Macroadenoma patients had a 33% operative cure
      rate, a 55% long term cure rate, and a recurrence rate of 33%. Thus, microadenoma
      and macroadenoma patients had similar long term cure rates, but macroadenoma
      patients required more aggressive adjuvant therapy (second surgery, radiation, or
      bromocriptine) and had higher rates of hypopituitarism (52% of macroadenoma
      patients vs. 0% of microadenoma patients required long term hormone replacement).

PMID- 7525628
TI  - Double blind trial comparing the effects of two doses of growth hormone in
      prepubertal patients with chronic renal insufficiency.
AB  - Growth retardation is a major problem for children with chronic renal
      insufficiency (CRI). Recent studies have convincingly shown that recombinant
      human GH accelerates growth significantly, but the optimal GH dose with regard to
      long term growth response and safety has not yet been established. GH therapy was
      given to 23 prepubertal children (18 boys and 5 girls; mean +/- SD age, 7.1 +/-
      3.6 yr; range, 1.6-14.1) with CRI and severe growth retardation in a double
      blind, dose-response trial. Patients were randomly assigned to either 2 or 4 IU
      GH/m2.day for 2.5 yr. During the first 6 months, there were comparable and
      significant increases in height velocity SD score for chronological age with both
      doses (P < 0.001). However, during the ensuing 2 yr, the higher GH dose induced a
      significantly greater improvement in height velocity SD score for chronological
      age than 2 IU GH. Catch-up growth was only sustained for 2.5 yr with 4 IU. In
      contrast, catch-up growth ceased after 6 months with 2 IU. Neither 2 nor 4 IU GH
      resulted in accelerated bone maturation during 2.5 yr of therapy. There was a
      significant increase in plasma insulin-like growth factor-I (IGF-I) levels with
      either dose, but significantly more so with 4 IU. Plasma IGF-II levels only
      increased significantly with 4 IU. The pretreatment elevation of IGF-binding
      protein-1 (IGFBP-1) levels decreased by 50% during the first study year with the
      higher GH dose, whereas there was no decrease with 2 IU. The elevated
      pretreatment IGFBP-3 levels increased comparably and significantly with either GH
      dose. Interestingly, only 4 IU resulted in a significantly greater increase in
      IGF-I than in IGFBP-3 levels. Regardless of GH dose, there was an insignificant
      decrease in fructosamine levels, whereas lipid and parathyroid concentrations
      remained constant. Renal function deterioration did not accelerate. GH therapy
      with 4 IU/m2.day induced and maintained catch-up growth during 2.5 yr in children
      with CRI without evidence of adverse effects. Bone maturation did not accelerate.
      This suggests that this higher GH dose may be beneficial for children with severe
      growth retardation secondary to CRI.

PMID- 7525625
TI  - The effects of human growth hormone (GH) administration in GH-deficient adults: a
      20-day metabolic ward study.
AB  - The early effects of human GH administration in GH-deficient (GHD) adults on
      protein, electrolyte homeostasis, and body composition were investigated in a
      metabolic ward study. Four patients were studied. In addition to a constant
      caloric and nitrogen (N)-sufficient diet, the patients received GH for 15 days in
      dosages of 12.5-25 micrograms/kg.day, with a maximum of 1.48 mg (4 IU)/day. GH
      replacement therapy was well tolerated by all patients. There was a slowly
      increasing effect on IGF-I levels, which reached a maximum after 8-12 days. The
      lowered IGFBP-3 levels normalized quicker, reaching maximum circulating
      concentrations 3 days after the start of GH treatment. Insulin concentrations
      maximally increased after 5 days, after which they leveled off. Insulin-like
      growth factor-binding protein-1 levels were maximally suppressed after 2 days of
      treatment. N balance became positive in all patients (mean, +2.8 +/- 0.2 g/day).
      Maximal N retention occurred after 2-5 days of GH administration, after which
      adaptation occurred. This degree of N retention represents a formation of 20 g
      muscle/day, which would mean an increase of 3.6 kg muscle over a period of 6
      months of GH replacement therapy. A rapidly occurring positive sodium balance was
      observed within 24-72 h. Maximal sodium retention amounted to 61 mmol/day. It
      slowly decreased spontaneously over the subsequent 12 days. In parallel, rapid
      changes in bioelectrical impedance analysis (BIA) were observed. There was a
      close parallel between the net cumulative sodium retention and the decrease in
      BIA in these patients during the first 15 days of GH therapy. This suggests that
      the calculation of body composition compartments on the basis of BIA measurements
      during the initial phase of GH replacement does not represent actual changes in
      fat mass. This was substantiated with measurements of body composition using dual
      energy x-ray absorptiometry. In conclusion, measurements of early metabolic
      changes in GHD adults during the first 15 days after the start of GH replacement
      indicate that IGF-I values reach maximal levels only after 8-12 days, that the
      measurements of changes in IGFBP-1 and IGFBP-3 levels probably do not contribute
      to a determination of the optimal GH replacement dose, that maximal N-retaining
      effects occur within 2-5 days, after which adaptation occurs, that massive sodium
      retention occurs during this period, which spontaneously levels off, and that
      cumulative sodium retention closely correlates during this period with changes in
      BIA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525629
TI  - Presence of immunoreactive corticotropin-releasing hormone in normal and
      polycystic human ovaries.
AB  - Recently, we demonstrated the presence of immunoreactive (Ir) CRH and its
      receptors in the rat ovary. To determine whether CRH is also present in human
      ovaries, we examined ovaries from normal women and patients with the polycystic
      ovarian syndrome (PCOS). Immunoreactive CRH in normal human ovaries had a similar
      distribution to that of rat ovarian IrCRH, as determined by immunohistochemistry.
      Thus, immunoreactivity was intense in the cytoplasm of thecal cells surrounding
      the ovarian follicles, in luteinized cells of the stroma, and in a subpopulation
      of cells within the corpora lutea. No IrCRH was present in oocytes of primordial
      follicles. Polycystic ovaries also had IrCRH in thecal cells; however, CRH
      immunostaining was less prominent or completely absent from the stroma or the
      sparsely present corpora lutea and was clearly detected in oocytes of primordial
      follicles. Using a specific RIA, the IrCRH content in extracts of normal ovaries
      was higher than that in polycystic ovaries (mean +/- SD, 0.075 +/- 0.02 vs. 0.038
      +/- 0.009 pmol/g wet tissue, respectively; P < 0.05). Human follicular fluid
      samples collected from women undergoing ovarian hyperstimulation for assisted
      reproduction had low, but detectable, levels of IrCRH (mean +/- SD, 4.975 +/-
      1.179 pmol/L), whereas IrCRH was undetectable in concurrently drawn plasma
      samples. IrCRH detected in normal and polycystic ovaries and in follicular fluid
      had similar chromatographic mobility to that of rat/human CRH-(1-41) by reverse
      phase HPLC. We conclude that IrCRH is present in normal human ovaries and
      follicular fluid, suggesting that this neuropeptide may play a regulatory role in
      one or more of the various functions of this gonad, such as ovulation and/or
      luteolysis, through its proinflammatory properties and/or its auto/paracrine
      regulation of steroid biosynthesis, in analogy to its action on testosterone
      secretion by the Leydig cell. Its decreased concentration and localization in
      primary oocytes of polycystic ovaries may be related to the increased androgen
      biosynthesis by the theca and stroma and/or to the oocyte dysfunction observed in
      women with the polycystic ovarian syndrome, respectively.

PMID- 7525630
TI  - Insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and
      proteolyzed IGFBP-3 in embryonic cavities in early human pregnancy: their
      potential relevance to maternal-embryonic and fetal interactions.
AB  - Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are
      believed to be important in fetal growth and development. In the current study,
      the developmental changes in the IGF and IGFBP axis were examined in 23 paired
      samples of human amniotic fluid (AF), extraembryonic coelomic (EEC) fluid, and
      maternal serum (MS) between 9 and 12 weeks gestation. Levels of IGF-I were very
      low in AF (7 +/- 3 ng/mL) and EEC (10 +/- 3 ng/mL) compared to those in MS (237
      +/- 42 ng/mL). In contrast, IGF-II concentrations were 210 +/- 36 and 174 +/- 22
      ng/mL in AF and EEC, respectively, and were approximately 25% of MS serum levels
      (884 +/- 122 ng/mL). There was no dependence on gestational age for either
      peptide in AF or EEC during the period of gestation examined. IGFBP-1 levels in
      AF increased about 20-fold (1.6 +/- 0.3 to 33.0 +/- 0.1 ng/mL) between 9 and 12
      weeks of pregnancy, and IGFBP-1 levels were nearly 2 orders of magnitude higher
      in EEC, increasing about 100-fold (365 +/- 119 to 3014 +/- 100.0 ng/mL) by the
      end of the first trimester. In contrast, IGFBP-1 levels were low in MS (24.9 +/-
      3.5 ng/mL) and showed no gestational age dependence. Using RIA, high levels of
      IGFBP-3 were found in EEC (2062 +/- 177 ng/mL) and MS (6590 +/- 357 ng/mL)
      compared to those in AF (152 +/- 24 ng/mL). Levels of IGFBP-3 in MS and EEC did
      not change significantly with gestational age, whereas an increase in IGFBP-1 was
      observed in AF after the tenth week of pregnancy. In contrast to high levels of
      IGFBP-3 in MS and EEC, determined by RIA, the 37- to 43-kilodalton IGFBP-3
      doublet was barely detectable by Western ligand blot analysis. This discrepancy
      suggested the presence of an IGFBP-3 protease in EEC, as has been found in MS,
      that decreases the affinity of this BP for IGF peptides and, therefore, renders
      it less readily detectable by Western ligand blot analysis. Using [125I]IGFBP-3
      as substrate, lower levels of IGFBP-3 protease activity were detected in EEC
      compared to MS, and nearly undetectable levels were found in AF. By Western
      immunoblotting, a smaller (28-kilodalton) immunoreactive form of IGFBP-3 was
      detected only in MS and EEC, suggesting proteolyzed IGFBP-3 in MS and EEC, but
      not in AF, during this gestational period.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525631
TI  - The insulin-like growth factor system in human peritoneal fluid: its effects on
      endometrial stromal cells and its potential relevance to endometriosis.
AB  - Peritoneal fluid (PF) lines the abdomen and pelvis and is believed to contain
      growth factors that stimulate endometriosis, a benign gynecological condition
      associated with pelvic pain and infertility, in which endometrial cells
      proliferate and differentiate on the pelvic peritoneum, outside of their normal
      location within the uterus. In this study, we examined the insulin-like growth
      factor (IGF) system in seven paired samples of PF and serum from normally cycling
      women and examined the mitogenic potential of this fluid on cultured endometrial
      stromal cells. IGF-I, IGF-II, and IGF-binding protein-1 (IGFBP-1), -2, -3, and -4
      were identified in PF by immunoassays. PF IGF levels, determined by RIA, were
      approximately 60% of paired serum levels, and PF levels of IGFBP-2 and IGFBP-3,
      determined by Western ligand blotting and RIA, respectively, were approximately
      half of their serum concentrations. IGFBP-4 was barely detectable by Western
      ligand blotting in PF, and levels of IGFBP-1, determined by immunoassay, were not
      appreciably different in PF and serum. Incubation of [125I]IGF-II with serum and
      PF and subsequent size-exclusion chromatography at neutral pH revealed
      approximately equal incorporation of radiolabel in the IGFBP regions of 150 and
      44 kilodaltons (kDa) in serum and primarily in the 44-kDa region in PF. RIA of
      IGFBP-3 in the IGFBP regions of column effluent revealed that the majority of
      IGFBP-3 was in the 150-kDa region in both serum and PF, suggesting the presence
      of the ternary complex in PF. Western ligand blotting of column effluent samples
      revealed 37-/43-kDa IGFBP-3 primarily in the 150-kDa complex in serum and a
      marked reduction in the amount of the 37-/43-kDa IGFBP in PF. Western
      immunoblotting of column effluent with IGFBP-3 antiserum revealed immunoreactive
      IGFBP-3 forms of 37-43 kDa (major) and 28 kDa (minor) in serum and almost
      exclusively the 28-kDa band in PF, suggesting that IGFBP-3 in PF may be
      proteolytically processed. The presence of an IGFBP-3 protease was confirmed
      using [125I]IGFBP-3 as substrate and was not appreciably present in paired serum
      samples. Inhibitor profiles demonstrated that this protease is a metal
      independent serine protease, and its approximate relative molecular mass was
      estimated to be 69 kDa, determined by size-exclusion chromatography. The
      mitogenic potential of IGF peptides and PF was assessed on cultured endometrial
      stromal cells to test the hypothesis that IGFs in PF may stimulate the growth of
      endometrium in the pelvic cavity, for example in the disorder of
      endometriosis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525632
TI  - Identification in human ovarian follicular fluid of proteins that share an
      epitope region unique to the extracellular domain of the follicle-stimulating
      hormone receptor.
AB  - Recently we identified a unique region, residues 9-30 in the extracellular domain
      of the FSH receptor, capable of binding FSH but not LH or TSH. We have shown that
      polyclonal antibodies raised against this region specifically recognized intact
      FSH receptors present on plasma membranes of cultured rat Sertoli cells. In the
      present study, plasma membranes from human granulosa-lutein cells were
      solubilized and subjected to sodium dodecyl sulfate polyacrylamide gel
      electrophoresis, followed by Western blot analysis. Antireceptor peptide
      antibody, but not preimmune serum control, recognized intact human FSH receptors,
      suggesting that human and rat FSH receptors share this unique N-terminus epitope
      region. Recent cloning studies have identified, in addition to full length
      receptor, the presence of FSH receptor-spliced messenger RNA variants, which
      encode receptor proteins with variable lengths of hydrophilic extracellular
      domains, but lacking transmembrane domains. Such proteins could theoretically
      represent secreted forms of the receptor. In this study, we used a polyclonal
      anti-FSH receptor (residues 9-30) peptide antibody to investigate whether FSH
      receptor-related soluble proteins might also be present in human ovarian
      follicular fluid (FF). In an enzyme-linked immunosorbent assay specific for the
      FSH receptor, antireceptor peptide antibody, but not preimmune serum serving as
      control, identified significant immunoreactivity in several human ovarian FF
      samples, suggesting that protein(s) present in FF share a common epitope with the
      extracellular domain of the FSH receptor. The apparent levels of FSH receptor
      related activity in FF samples, expressed relative to the FSH receptor (residues
      9-30) peptide, ranged from 31-55 ng/mL. Passing of the samples through 0.22
      micron filters or subjecting the samples to high speed centrifugation did not
      alter the activity profiles of the samples ruling out effects due to
      contamination with plasma membranes from granulosa cells. When human FF samples
      were subjected to gel permeation chromatography, at least four distinct protein
      peaks were resolved, in the molecular mass range between 70-460 kilodaltons, each
      of which was recognized by the FSH receptor 9-30 peptide antibodies. Our results
      provide initial evidence for the presence in human ovarian FF of proteins sharing
      epitope with the extracellular domain of the FSH receptor and presumably derived
      from the granulosa cell. Since we have previously shown that the epitope region,
      represented by residues 9-30 in the extracellular domain of the FSH receptor
      specifically binds FSH, the proteins in human FF sharing this epitope may have
      functional significance.

PMID- 7525634
TI  - Identification of insulin-like growth factor-binding protein-3 (IGFBP-3)
      fragments and IGFBP-5 proteolytic activity in human seminal plasma: a comparison
      of normal and vasectomized patients.
AB  - Previous studies have demonstrated that insulin-like growth factor (IGF)
      peptides, IGF-binding proteins (IGFBPs), and IGFBP-3 proteolytic activity, are
      present in human seminal plasma (SP). In this study, we have further
      characterized the IGFBPs in SP using immunoprecipitation and Western ligand
      blotting, Western immunoblotting, affinity cross-linking and immunoprecipitation,
      and RIA of IGFBP-3 using two different assays and have identified additional
      proteolytic activities for IGFBP-4 and IGFBP-5 in SP. Immunoprecipitation with
      antibodies to IGFBP-2, IGFBP-3, and IGFBP-4, before and after affinity cross
      linking, demonstrated that intact IGFBP-2 and IGFBP-4 are present in SP, but
      intact IGFBP-3 is absent. Low mol wt fragments of IGFBP-3, which did not bind to
      IGF-I or IGF-II on Western ligand blot and did not cross-link to IGF-II, were
      demonstrated on Western immunoblot and were measurable by two different RIAs.
      Proteolytic activities for IGFBP-4 and IGFBP-5 were demonstrated in SP by
      incubation with the respective iodinated IGFBPs. On comparing the proteolytic
      activity for IGFBP-4 by purified prostate-specific antigen (PSA; a known IGFBP-3
      protease in SP) or by SP with measured equivalent concentrations of PSA, the dose
      response and fragment patterns were identical. With IGFBP-5, however, proteolysis
      by purified PSA was different from that by SP with measured equivalent
      concentrations of PSA: 1) proteolysis by pure PSA was less efficient than matched
      concentrations of SP; 2) the pattern of fragments after proteolysis by pure PSA
      was different from that after proteolysis by matched concentrations of SP; and 3)
      proteolysis by purified PSA was significantly inhibited by
      phenylmethylsulfonylfluoride and aprotinin, but proteolysis by SP was not. We
      conclude that human SP contains intact IGFBP-2 and IGFBP-4, but has only IGFBP-3
      fragments with low affinity for IGF peptides; that PSA is able to proteolyze
      IGFBP-4 and IGFBP-5 (as well as IGFBP-3); and that an additional IGFBP-5 protease
      is probably present in SP. There was no significant difference in any of these
      findings in SP from normal volunteers, vasectomized patients, or patients with
      idiopathic azoospermia. The roles of IGFBPs and IGFBP proteases in the male
      reproductive system and male infertility remain to be further elucidated.

PMID- 7525633
TI  - Effect of recombinant human growth hormone on the muscle strength response to
      resistance exercise in elderly men.
AB  - Normal aging is characterized by detrimental changes in body composition, muscle
      strength, and somatotropic function. Reduction in muscle strength contributes to
      frailty and risk for fracture in the elderly. Although older adults increase
      muscle strength as a result of resistance exercise training, the strength gains
      quickly level off, with only modest increases thereafter despite continued
      training. To investigate whether age-related deficits in the somatotropic axis
      limit the degree to which muscle strength can improve with resistance training in
      older individuals, we conducted a double blind, placebo-controlled exercise
      trial. Eighteen healthy elderly men (65-82 yr) initially underwent progressive
      weight training for 14 weeks to invoke a trained state. Subjects were then
      randomized to receive either 0.02 mg/kg BW.day recombinant human GH (rhGH) or
      placebo, given sc, while undertaking a further 10 weeks of strength training.
      Sequential measurements were made of muscle strength (one repetition maximum),
      body composition (dual energy x-ray absorptiometry), and circulating levels of
      insulin-like growth factor-I (IGF-I) and IGF-binding protein-3. For each
      exercise, strength increased for both groups (P = 0.0001) through 14 weeks of
      training, with little improvement thereafter. Increases in muscle strength ranged
      from 24-62% depending on the muscle group. Baseline plasma IGF-I concentrations
      were similar in both groups (mean +/- SEM, 106 +/- 9 micrograms/L), approximately
      half that observed in healthy young adults. In the rhGH group, IGF-I levels
      increased to 255 +/- 32 micrograms/L at week 15 and 218 +/- 21 micrograms/L at
      week 24 (P < 0.001). In the placebo group, IGF-I increased slightly to 119 +/- 6
      micrograms/L at 24 weeks. IGF-binding protein-3 also increased in the rhGH group
      (P < 0.05). rhGH had no effect on muscle strength at any time, and no systematic
      difference in muscle strength was observed between groups throughout the study.
      Body weight did not change in either group, but lean body mass increased, and fat
      mass decreased (P < 0.05) in the rhGH group. Supplementation with rhGH does not
      augment the response to strength training in elderly men. These results suggest
      that deficits in GH secretion do not underlie the time-dependent leveling off of
      muscle strength seen with training in the elderly and provide no support for the
      popular view of GH as an ergogenic aid.

PMID- 7525637
TI  - Localization of messenger ribonucleic acid for insulin-like growth factor-binding
      proteins in human skin by in situ hybridization.
AB  - The role of the insulin-like growth factors (IGFs) in human skin physiology has
      been increasingly recognized, although relatively little is known about the cell
      types involved or the cellular mechanisms that mediate these responses. Epidermal
      keratinocytes and dermal fibroblasts both possess IGF-I receptors and are
      responsive to IGF-I. IGF-binding proteins (IGFBPs), known modulators of IGF
      action, may also be responsible for targeting IGF-I to its receptors and are
      produced by both cultured keratinocytes and fibroblasts. To demonstrate sites of
      production of IGFBPs in human skin, we have used in situ hybridization to
      localize messenger ribonucleic acid (mRNA) for the six IGFBPs. Antisense and
      sense RNA probes for the IGFBPs (IGFBP-1 to -6) were produced, and 5-microns
      sections of normal adult human male chest skin were probed. The control probe
      used was keratin-5, which is known to hybridize to the basal keratinocytes of the
      epidermis. mRNAs for human IGFBP-2, -3, -4, and -5 were identified, with mRNAs
      for IGFBP-2 and IGFBP-4 localized in sebaceous glands and eccrine sweat glands
      (epidermal origin), IGFBP-3 mRNA in the basal layer of the epidermis and mRNAs
      for IGFBP-4, and IGFBP-5 found throughout the dermis. mRNAs for IGFBP-1 and -6
      were not identified in human skin. These studies demonstrate specific
      localization of IGFBP mRNAs in adult human skin, suggesting that each IGFBP may
      play a specific role in targeting IGF-I to its receptor on responsive cells and,
      ultimately, in modulation of IGF-I action in skin.

PMID- 7525636
TI  - Insulin-like growth factor axis abnormalities in prostatic stromal cells from
      patients with benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown
      etiology. To assess whether patients with BPH have alterations in their prostatic
      IGF axis, we measured the expression (by Northern blotting) and the production
      (by Western ligand blotting and RIA) of insulin-like growth factor-II (IGF-II)
      and IGF-binding proteins (IGFBPs) in prostatic epithelial and stromal cell
      strains grown from normal (n = 7), hyperplastic (n = 7), and malignant (n = 5)
      surgical specimens. Levels of IGF-II messenger ribonucleic acid (mRNA; normalized
      for actin expression) were 10-fold higher in BPH stromal cell strains compared to
      those in normal stromal cell strains (P < 0.0001). Western ligand blotting of
      conditioned medium (CM) from normal stromal cells demonstrated the presence of
      IGFBP-2, -3, and -4. In the CM of BPH stromal cells, IGFBP-2 levels were
      dramatically reduced to less than 20% of normal (P < 0.001). Additionally, IGFBP
      5, which was not observed in significant amounts in normal stromal cell-CM, was
      found in large quantities in BPH stromal cell-CM. Northern blot analysis of mRNA
      from normal and BPH stromal cells demonstrated a 5-fold decrease in IGFBP-2 mRNA
      (P < 0.001) and a 4-fold increase in IGFBP-5 mRNA (P < 0.01) in BPH compared to
      normal cells. In prostate stromal cells from cancer specimens, no abnormalities
      were found. No abnormalities were observed in the IGF axis parameters evaluated
      in prostate epithelial cells from BPH or cancer strains. We conclude that
      prostatic stromal cell strains isolated from patients with BPH hyperexpress the
      mRNA for IGF-II and IGFBP-5 while expressing reduced amounts of IGFBP-2 mRNA.
      IGFBP, but not IGF-II, peptide levels in CM correspond to the mRNA differences.
      This is the first documentation of altered gene and protein expression in this
      common disease. We speculate that these abnormalities in the IGF axis may be
      important in the pathogenesis of BPH.

PMID- 7525635
TI  - Alteration in insulin-like growth factor-binding proteins (IGFBPs) and IGFBP-3
      protease activity in serum and urine from acute and chronic renal failure.
AB  - The insulin-like growth factors, IGF-I and IGF-II, are proteins that promote
      cellular growth and differentiation of various organs, including the kidney.
      These peptides interact with high affinity cell surface receptors and bind to a
      family of IGF-binding proteins (IGFBPs). Altered serum and urinary IGFBP patterns
      in children with chronic renal failure have been previously described. In this
      study, we evaluated serum and urinary IGFBP profiles in acute renal failure
      patients (ARF; n = 10) and chronic renal failure patients (n = 10), using Western
      ligand blots. Most patients with acute or chronic renal failure showed decreased
      intact serum IGFBP-3 and increased serum IGFBP-2. Both groups displayed marked
      urinary IGFBP alterations, including increased urinary IGFBP-1 and totally absent
      urinary IGFBP-3, as detected by Western ligand blot. To evaluate altered IGFBP
      profiles, we performed IGFBP-3 protease assays with sera and urine from renal
      failure patients and normal controls. Although control urine had only minor
      protease activity (defined by the ability to degrade [125I]IGFBP-3), significant
      protease activity was found in urine from renal failure patients. The proteolytic
      pattern and susceptibility to protease inhibitors in most renal failure urine
      samples were the same as those seen in normal urine and with plasmin. Protease
      activity was completely inhibited by serine protease inhibitors. We speculate
      that urinary protease activity is mediated primarily by a serine protease(s),
      which may be involved in the modulation of renal IGF activity in health and
      disease.

PMID- 7525638
TI  - Reversible effects of cessation and recommencement of thyroxine treatment on
      insulin-like growth factors (IGFs) and IGF-binding proteins in patients with
      total thyroidectomy.
AB  - There is a complex relationship between the thyroid and pituitary GH/insulin-like
      growth factor (IGF) axes. IGFs circulate in association with six specific high
      affinity binding proteins (IGFBPs) that modulate their bioactivity and
      bioavailability. Recent evidence suggests that gene expression and circulating
      levels of IGFBPs are related to prevailing thyroid hormone status. We have
      investigated the effects of both withdrawal and reinstitution of thyroid hormone
      replacement on circulating IGF and IGFBP levels in athyreotic patients (n = 10).
      The mean IGF-I concentration fell from a basal level of 191.8 +/- 12 micrograms/L
      to a nadir of 136.4 +/- 17.8 micrograms/L (P = 0.026) 5 weeks after stopping T4
      treatment and returned to normal values 3 weeks after recommencement of
      replacement treatment. The fall in IGF-II levels followed a similar pattern from
      a basal mean level of 649 +/- 33.7 to 547 +/- 42.7 micrograms/L (P = 0.026) at 5
      weeks. These changes paralleled the fall in free T3 and free T4. Similarly, IGFBP
      1 levels fell after stopping T4 treatment from a basal level of 54.8 +/- 4.0 to
      24.6 +/- 7.0 micrograms/L (P = 0.001) 5 weeks later. After T4 treatment was
      restarted, IGFBP-1 levels rose and were not significantly different from basal
      values by week 8. There were strong positive correlations between paired data
      sets for IGFBP-1 and free T3 (r = 0.488; P = 0/0037) and free T4 (r = 0.56; P =
      0.0006), and a strong negative correlation with TSH (r = -0.515; P = 0.0001).
      Insulin is known to be important in the regulation of IGFBP-1, but no changes in
      fasting insulin levels during T4 withdrawal were noted, and levels of IGFBP-1 did
      not exhibit the normal inverse relationship with circulating insulin levels.
      Levels of IGFBP-2, assessed by Western ligand blotting, increased during the
      development of hypothyroidism, peaked 5 weeks after stopping T4 replacement, and
      declined on reinstitution of replacement treatment. A further level of regulation
      of the IGF-IGFBP axis is afforded by the presence of specific circulating IGFBP
      proteases. Proteases directed against IGFBP-3 proteolytically cleave the major
      carrier BP in the circulation and reduce its binding affinity, possibly resulting
      in increased tissue IGF bioavailability. Despite the marked reduction in
      circulating IGF levels and the generation of significant biochemical
      hypothyroidism, IGFBP-3 protease activity was not apparent during the 10-week
      period of the study.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525640
TI  - Laterality of mental imagery generation and operation: tests with brain-damaged
      patients and normal adults.
AB  - The relationships between hemispheric function and components of the imagery
      process were examined in patients with unilateral right and left brain damage and
      in intact adult subjects. In the image generation condition, subjects were
      required to mentally generate Katakana letters corresponding to Hiragana letters
      displayed on a CRT. The results for the intact adults suggested a left hemisphere
      superiority, but the unilaterally brain-damaged subjects showed no hemispheric
      difference in this task. In the imagery operation task (transformation or lateral
      translation), subjects were asked to find a genuine Kanji among distractors
      (pseudo-Kanji) that were constructed from two Kanji radicals (themselves real
      Kanji) that were either displayed in reverse order or shifted apart. The results
      for both intact adults and patients with unilateral brain damage suggest the
      superiority of the right hemisphere.

PMID- 7525639
TI  - Interhemispheric balance patterns detected by selective phonemic dichotic
      laterality measures in four clinical subtypes of reading-disabled children.
AB  - Identifying disabilities in word-attack, word-recognition, or reading
      comprehension, allowed for four categories of reading disability: (1) reading
      comprehension only (RC), (2) word-attack plus comprehension (WA+RC), (3) word
      attack, word-recognition, and comprehension (WA+WR+RC), and (4) word-attack but
      not comprehension (WA-RC). Along with age-matched controls (AMC) and
      developmental-delay controls (DDC), the disabled were tested on a directed
      attention dichotic task using consonant-vowel combinations. Laterality results
      for each place of articulation (i.e., bilabial, alveolar, and velar) selectively
      attested to greater left hemisphere involvement or engagement for the RC group
      and greater right hemisphere involvement or engagement for the WA+RC group.
      Performance of the other two disabled groups was consistent with less efficient
      right hemisphere involvement or callosal transfer. Implications for theory,
      research, and remediation are discussed.

PMID- 7525641
TI  - Uveitogenic T lymphocytes in the rat: pathogenicity vs. lymphokine production,
      adhesion molecules and surface antigen expression.
AB  - A possible correlation between the pathogenicity of autoimmune T cells and their
      lymphokine production, expression of functional adhesion molecules and expression
      of some surface antigens was examined. We used four retinal antigen-specific
      Lewis rat T cell lines and sublines: one specific to the major pathogenic epitope
      of the human retinal soluble antigen (S-Ag; residues 337-356), and three specific
      to the major pathogenic epitope of the bovine interphotoreceptor retinoid binding
      protein (IRBP; residues 1177-1191). The lines have different degrees of
      uveitogenicity, from highly pathogenic to nonpathogenic. All four T cell lines
      produced roughly equivalent amounts of interferon-gamma, lymphotoxin/tumor
      necrosis factor (TNF alpha/beta), interleukin-3, interleukin-6 and transforming
      growth factor-beta. Interleukin-4 activity could not be detected. The lines also
      expressed similar levels of functional adhesion molecules, as measured by binding
      to cultured rat aorta endothelial cells. The nonpathogenic subline, however, was
      the lowest responder to antigenic stimulation with respect to proliferation and
      interleukin-2 production. Examination of cell surface antigens showed that in
      contrast to the other lines, the majority of cells in the nonpathogenic subline
      lacked detectable expression of CD4. No difference was found in the level of
      expression of the IL-2 receptor and T cell antigen receptor among the four lines.
      Because CD4 is the restricting element in these lines, reduced CD4 expression in
      the nonpathogenic subline may at least partially explain its poor response in
      vitro to antigenic stimulation. All three attributes could be connected to lack
      of pathogenicity of this line in vivo. These results support the contention that
      class II-restricted recognition of autoantigen within the neuroretina by
      uveitogenic T lymphocytes must occur as an initial step in the pathogenesis of
      EAU. A defect in this step will preclude pathogenesis regardless of some other
      functional attributes possessed by effector T cells, such as production of
      inflammatory lymphokines and expression of adhesion molecules.

PMID- 7525642
TI  - Antibodies against sulfated glycosphingolipids of peripheral nerve myelins
      detected in patients with human cytomegalovirus infection.
AB  - In this paper we studied whether cytomegalovirus (CMV) infection could induce a
      production of antibodies against PNS glycosphingolipids (GL). Sera from patients
      with congenital CMV infection were tested for IgM and IgG antibodies against
      acidic and neutral GL purified from human PNS. TLC-immunostaining assay revealed
      that the CMV-infected patients' sera contained antibodies against sulfoglucuronyl
      glycosphingolipids (SGGL), which also bound to other sulfatide with a low
      affinity. No reactivity was observed to PNS gangliosides or neutral GL. The
      antibody also bound to other sulfated glycolipids including seminolipid and
      LacCer-sulfate, but not to cholesterol-sulfate, suggesting that a sulfated sugar
      chain may be important for their low-affinity binding. Furthermore, both anti
      sulfatide and anti-SGGL antibodies were absorbed with sulfatide-conjugated octyl
      Sepharose and heparin-Sepharose columns, whereas CMV-specific IgG titer was not
      decreased by the absorption of anti-sulfated GL antibody. These results suggest
      that CMV infection might specifically induce production of antibodies against
      sulfated GL, whereas these antibodies differed from CMV-specific antibody.

PMID- 7525643
TI  - Specificity and structure of murine monoclonal antibodies against GM1
      ganglioside.
AB  - Anti-GM1 antibodies have been implicated in the pathogenesis of several
      neurological diseases, but the role of these antibodies is still controversial.
      An animal model could provide insight into the mechanisms of these human
      disorders, but obtaining specific anti-GM1 monoclonal antibodies (mAbs) has been
      extremely difficult because of the weak immunogenicity of GM1 ganglioside. Four
      murine mAbs against GM1 were elicited by immunization of mice with lyso GM1
      coupled to BSA and GM1 glycolipid. All four IgM,k mAbs bound strongly to GM1,
      three antibodies (125, 360 and 494) also bound very weakly to asialo GM1 (GA1)
      and one (156) bound weakly to GD1b. Three antibodies (125, 360 and 494) were
      encoded by the same VH and V kappa genes. The VH gene exhibited 97% homology to
      VHOX1, a member of the VHQ52N gene family, the D segment was probably derived
      from DQ52 and JH was identical to JH2. The V kappa gene was approximately 99%
      homologous to V kappa RF and J kappa was germline J kappa 2. The VH gene of mAb
      156 exhibited 98% homology to VH205.12, of the VHJ558 gene family, the D segment
      was derived from DFL16.1, and JH was germline JH2. The V kappa and J kappa genes
      of mAb were identical to V kappa 8 and J kappa 1, respectively. The genes
      encoding these anti-GM1 antibodies were close to germline sequences and have been
      used to encode other antibodies. This suggests that the unresponsiveness of mice
      to immunization is probably due to inactivation of self-reactive B cells. These
      rare anti-GM1 mAbs will be valuable reagents for studies of the pathogenesis of
      autoimmune neuropathy in animals, and also for analyzing the tissue distribution
      and functions of GM1.

PMID- 7525644
TI  - Lysis of rat brain microvascular endothelial cells mediated by resting but not
      activated MBP-specific CD4+ T cell lines.
AB  - Previous work from this laboratory showed that the encephalitogenic potential of
      myelin basic protein (MBP)-specific T cells is inseparably associated with their
      cytotoxic potential. MBP-specific T cells lyse all cells that present
      autoimmunogenic MBP peptide in context of appropriate MHC class II determinants.
      Beside class II-induced glia cells, blood-brain barrier-derived endothelial cells
      were identified as highly susceptible target cells for cytotoxic MBP-specific T
      cells. Here we show that the cytotoxic reaction against endothelial cells
      essentially differs from cytotoxicity against other target cells. In contrast to
      classical T cell-mediated lytic responses, which are most efficiently executed by
      activated T cells, rat brain endothelium (RBE) lysis could only be mediated by
      resting T cells. Activated MBP-specific T cell blasts were not able to mediate
      strong RBE lysis. Furthermore, T cell lines with specificities for protein
      antigens other than MBP did not cause RBE lysis. A role of the cytolytic capacity
      of resting MBP-specific T cells in the pathogenesis of experimental autoimmune
      encephalomyelitis is probable.

PMID- 7525647
TI  - De novo generation of permanent neovascularized soft tissue appendages by
      platelet-derived growth factor.
AB  - Treatment of wounds with pharmacologic doses of the BB homodimeric form of
      recombinant PDGF (rPDGF-BB) induces the recruitment, activation, and
      proliferation of mesenchymal cells, resulting in the deposition of provisional,
      and subsequently collagen-containing extracellular matrix. In preliminary
      experiments with an in vitro growth chamber model in the rat consisting of a
      silicone shell containing a dissected femoral vascular bundle, we found that
      rPDGF-BB incorporated into a rapidly dissolving collagen type I film induces the
      generation of a marked, but transient amount of de novo tissue around the femoral
      vascular bundle. In the present studies, the new tissue generated around the
      femoral vascular bundle was wrapped with a full thickness syngeneic skin graft to
      determine if functional support of the graft would lead to sustained maintenance
      of the underlying generated tissue and create an epithelialized soft tissue
      appendage. The tissue generated after a single application of rPDGF-BB was skin
      grafted on the 10th day, exteriorized 20 d later, and observed for an additional
      month. This led to the formation of soft tissue appendages which demonstrated
      marked neovascularization, fibroblast migration and proliferation, and increased
      glycosaminoglycan, fibronectin, and collagen fibril deposition, now leading to
      preservation of the newly generated tissue. In contrast, minimal new tissue was
      generated in control-treated vascular bundles or bundles treated with inactive
      PDGF-BB, and grafting with skin failed to sustain the underlying tissue. Thus,
      rPDGF-BB coupled with skin grafting induced the formation of functional large
      soft tissue appendages which are potentially useful clinically to fill tissue
      defects or to serve as a cell delivery system for transfected genes.

PMID- 7525648
TI  - Expression and distribution of aquaporin of collecting duct are regulated by
      vasopressin V2 receptor in rat kidney.
AB  - To examine whether expression and distribution of aquaporin of collecting duct
      (AQP-CD) are regulated by vasopressin V2 receptor (V2R), we performed
      immunohistochemical studies with specific antibody against AQP-CD. Normal Wistar
      rats were divided into four groups and treated for 3 d; control, dehydration,
      vasopressin V1 receptor (V1R) antagonist (OPC-21268 120 mg/kg), V2R antagonist
      (OPC-31260 30 mg/kg). At time of death, urine osmolality (Uosm) in the
      dehydration group (1884 +/- 245 mOsm/kg) was significantly higher than that in
      the control (938 +/- 91). In the V2R antagonist group, Uosm was significantly
      decreased to 249 +/- 29, whereas V1R antagonist showed no effect on Uosm. In the
      control and V1R antagonist groups, immunofluorescence studies showed the AQP-CD
      staining of both apical membrane and subapical cytoplasm of CD cells of the
      cortex and the inner medulla. Dehydration increased the immunostaining of both
      apical membrane and subapical cytoplasm of CD cells of the inner medulla, and the
      degree of increase was dominant in apical membrane. In the V2R antagonist group,
      only faint staining of apical membrane and weak labeling of cytoplasm of CD cells
      of the inner medulla were observed. These changes in the localization and protein
      amount of AQP-CD by dehydration and V2R antagonist were quantitatively confirmed
      by immunogold studies and immunoblot analysis of the inner medulla. The present
      results indicate that the distribution and amount of AQP-CD in the CD cells are
      regulated by vasopressin V2 receptor.

PMID- 7525646
TI  - Block of AIDS-Kaposi's sarcoma (KS) cell growth, angiogenesis, and lesion
      formation in nude mice by antisense oligonucleotide targeting basic fibroblast
      growth factor. A novel strategy for the therapy of KS.
AB  - Kaposi's sarcoma (KS) is the most frequent tumor of HIV-1-infected individuals
      (AIDS-KS). Typical features of KS are proliferating spindle-shaped cells,
      considered to be the tumor cells of KS, and endothelial cells forming blood
      vessels. Basic fibroblast growth factor (bFGF), a potent angiogenic factor, is
      highly expressed by KS spindle cells in vivo and after injection in nude mice it
      induces vascular lesions closely resembling early KS in humans. Similar lesions
      are induced by inoculating nude mice with cultured spindle cells from AIDS-KS
      lesions (AIDS-KS cells) which produce and release bFGF. Here we show that
      phosphorothioate antisense (AS) oligonucleotides directed against bFGF mRNA
      (ASbFGF) inhibit both the growth of AIDS-KS cells derived from different patients
      and the angiogenic activity associated with these cells, including the induction
      of KS-like lesions in nude mice. These effects are due to the block of the
      production of bFGF which is required by AIDS-KS cells to enter the cell cycle and
      which, after release, mediates angiogenesis. The effects of ASbFGF are specific,
      dose dependent, achieved at low (0.1-1 microM), nontoxic, oligomer
      concentrations, and are reversed by the addition of bFGF to the cells, suggesting
      that ASbFGF oligomers are promising drug candidates for KS therapy.

PMID- 7525645
TI  - The pathophysiologic role of alpha 4 integrins in vivo.

PMID- 7525649
TI  - Inhibition of sphincter of Oddi function by the nitric oxide carrier S-nitroso-N
      acetylcysteine in rabbits and humans.
AB  - Nitric oxide (NO) is an inhibitor of gastrointestinal smooth muscle. Model
      systems of the gut predict the NO will complex with biological thiol (SH) groups,
      yielding S-nitrosothiols (RS-NO), which may limit the propensity to form
      mutagenic nitrosamines. The inhibitory effects of NO and its biologically
      relevant adducts on sphincter of Oddi (SO) motility have been inferred from
      animal studies; however, their importance in regulating human SO is not known.
      The objectives of this study were to (a) provide histologic confirmation of
      nitric oxide synthase (NOS) in human SO; (b) characterize the pharmacology of S
      nitroso-N-acetylcysteine (SNAC), an exemplary S-nitrosothiol, on SO motility in a
      rabbit model; and (c) study the effects of topical SNAC on SO motility in humans.
      Immunocytochemical and histochemical identification of NOS was performed in human
      SO. The pharmacologic response of SNAC was defined in isolated rabbit SO using a
      standard bioassay. Topical SNAC was then applied to the duodenal papilla in
      patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and
      biliary manometry. NOS was localized to nerve fibers and bundles of the SO in
      rabbits and humans. SNAC inhibited spontaneous motility (frequency and amplitude)
      as well as acetylcholine-induced elevations in SO basal pressure in the rabbit
      model. In patients undergoing ERCP and biliary manometry, topical SNAC inhibited
      SO contraction freqency, basal pressure, and duodenal motility. NOS is localized
      to neural elements in human SO, implicating a role for NO in regulating SO
      function. Supporting this concept, SNAC is an inhibitor of SO and duodenal
      motility when applied topically to humans during ERCP. Our data suggest a novel
      clinical approach using local NO donors to control gastrointestinal motility and
      regulate sphincteric function.

PMID- 7525650
TI  - Effect of gold sodium thiomalate and its thiomalate component on the in vitro
      expression of endothelial cell adhesion molecules.
AB  - Endothelial adhesion molecules play an important role in the tissue recruitment
      of leukocytes in inflammatory conditions such as rheumatoid arthritis. We have
      investigated the effect of the antirheumatic drug gold sodium thiomalate on
      adhesion molecule protein and mRNA expression in cultured human endothelial
      cells. Gold sodium thiomalate inhibited cytokine (TNF, IL-1, IL-4)-stimulated
      expression of vascular cell adhesion molecule-1 and E-selectin but not
      intercellular adhesion molecule-1 on endothelial cells. Gold sodium thiomalate
      also suppressed TNF-stimulated increases in vascular cell adhesion molecule-1 and
      E-selectin mRNA levels but had no effect on intercellular adhesion molecule-1
      mRNA. Thiomalate (mercaptosuccinate), but not gold thioglucose or D
      penicillamine, mimics the effect of gold sodium thiomalate at equimolar
      concentrations. We propose that the inhibition of vascular cell adhesion molecule
      1 and E-selectin expression by gold sodium thiomalate is due to its thiomalate
      and not its gold component. Gold sodium thiomalate has a direct effect on
      endothelial adhesion molecule expression, and this may contribute to its
      antiinflammatory activity.

PMID- 7525651
TI  - Effects of relaxin on mast cells. In vitro and in vivo studies in rats and guinea
      pigs.
AB  - The results of the current study demonstrate that relaxin inhibits histamine
      release by mast cells. This effect is related to the peptide concentrations, and
      could be observed in both isolated rat serosal mast cells stimulated with
      compound 48/80 or calcium ionophore A 23187, and in serosal mast cells isolated
      from sensitized guinea pigs and challenged with the antigen. The morphological
      findings agree with the functional data, revealing that relaxin attenuates
      calcium ionophore-induced granule exocytosis by isolated rat serosal mast cells.
      Similar effects of relaxin have also been recognized in vivo by light microscopic
      and densitometric analysis of the mesenteric mast cells of rats which received
      the hormone intraperitoneally 20 min before local treatment of the mesentery with
      calcium ionophore. Moreover, evidence is provided that relaxin stimulates
      endogenous production of nitric oxide and attenuates the rise of intracellular
      Ca2+ concentration induced by calcium ionophore. The experiments with drugs
      capable of influencing nitric oxide production also provide indirect evidence
      that the inhibiting effect of relaxin on mast cell histamine release is related
      to an increased generation of nitric oxide. It is suggested that relaxin may have
      a physiological role in modulating mast cell function through the L-arginine
      nitric oxide pathway.

PMID- 7525652
TI  - Blast cell methotrexate-polyglutamate accumulation in vivo differs by lineage,
      ploidy, and methotrexate dose in acute lymphoblastic leukemia.
AB  - High-dose methotrexate (HDMTX) is a component of most treatment protocols for
      childhood acute lymphoblastic leukemia (ALL), yet recent studies of receptor
      mediated transport and saturable polyglutamylation have questioned its rationale.
      To investigate this in vivo, methotrexate and its active polyglutamated
      metabolites (MTX-PG) were measured in bone marrow blasts obtained from 101
      children randomized to single-agent therapy with either HDMTX (1 g/m2 per 24 h
      i.v., n = 47) or low-dose MTX (LDMTX, 30 mg/m2 by mouth every 6 h x 6, n = 54),
      before remission induction therapy. Blast concentrations of total MTX-PGs (median
      460 vs 1380 pmol/10(9) cells) and of long-chain MTX-glu4-6 were both
      significantly higher after HDMTX (P < 0.001). With either treatment, MTX-PGs were
      significantly higher in B-lineage blasts than in T-lineage blasts (LDMTX P =
      0.001, HDMTX P = 0.03). In a multiple regression analysis of B-lineage ALL, blast
      MTX-PG was significantly related to MTX dose (or plasma MTX concentration),
      lymphoblast ploidy (hyperdiploid > nonhyperdiploid), and percentage S-phase. This
      is the first evidence that HDMTX achieves higher MTX-PG concentrations in ALL
      blasts in vivo, establishing a rationale for HDMTX in the treatment of childhood
      ALL, especially T-lineage or nonhyperdiploid B-lineage ALL, disease
      characteristics associated with a poor prognosis on conventional therapy.

PMID- 7525653
TI  - Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and
      migration in vitro promoted by substance P.
AB  - We evaluated the effects of nitric oxide (NO) generators and endogenous
      production of NO elicited by substance P (SP) in the angiogenesis process.
      Angiogenesis was monitored in the rabbit cornea in vivo and in vitro by measuring
      the growth and migration of endothelial cells isolated from coronary
      postcapillary venules. The angiogenesis promoted in the rabbit cornea by [Sar9]
      SP-sulfone, a stable and selective agonist for the tachykinin NK1 receptor, and
      by prostaglandin E1 (PGE1), was potentiated by sodium nitroprusside (SNP).
      Conversely, the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L
      NAME), given systemically, inhibited angiogenesis elicited by [Sar9]-SP-sulfone
      and by PGE1. Endothelial cells exposed to SNP exhibited an increase in thymidine
      incorporation and in total cell number. Exposure of the cells to NO generating
      drugs, such as SNP, isosorbide dinitrate, and glyceryl trinitrate, produced a
      dose-dependent increase in endothelial cell migration. Capillary endothelial cell
      proliferation and migration produced by SP were abolished by pretreatment with
      the NO synthase inhibitors N omega-mono-methyl-L-arginine (L-NMMA), N omega-nitro
      L-arginine (L-NNA), and L-NAME. Exposure of the cells to SP activated the calcium
      dependent NO synthase. Angiogenesis and endothelial cell growth and migration
      induced by basic fibroblast growth factor were not affected by NO synthase
      inhibitors. These data indicate that NO production induced by vasoactive agents,
      such as SP, functions as an autocrine regulator of the microvascular events
      necessary for neovascularization and mediates angiogenesis.

PMID- 7525655
TI  - Recombinant soluble form of the human high-affinity immunoglobulin E (IgE)
      receptor inhibits IgE production through its specific binding to IgE-bearing B
      cells.
AB  - A recombinant soluble form of the alpha subunit of the human high-affinity
      receptor for IgE (rsFc epsilon RI alpha), one of the potent IgE-binding
      molecules, was tested for its ability to regulate IL-4-induced IgE synthesis by
      human lymphocytes. Addition of rsFc epsilon RI alpha to cultures induced a dose
      dependent inhibition of the T cell-dependent and independent synthesis of IgE.
      The suppression of IgE synthesis was observed at the protein and the mRNA levels,
      and it was IgE class specific. By flow cytometry, specific binding of rsFc
      epsilon RI alpha was detected on surface IgE-bearing B cells as well as on U266
      cells, and it was completely blocked by preincubation with IgE. rsFc epsilon RI
      alpha bound to the cell surface IgE could be effectively dissociated not only by
      a large excess of IgE, but also by an anti-rsFc epsilon RI alpha mAb that
      competes with IgE for the binding to rsFc epsilon RI alpha. This mAb abolished
      the rsFc epsilon RI alpha-mediated suppression of IgE synthesis. These data
      suggest that rsFc epsilon RI alpha may have a function in selectively suppressing
      IgE synthesis through its interaction with the membrane-bound form of IgE.

PMID- 7525656
TI  - Acoustic rhinometry: rationale and perspectives.
AB  - Acoustic rhinopharyngometry provides a new, non-invasive access to upper airways
      geometry. In this experimental and clinical study the diagnostic value of
      acoustic rhinopharyngometry was investigated. In vitro measurements showed
      adequate accuracy, reliability and spatial resolution within the range of nasal
      and epipharyngeal dimensions. Clinical measurements confirmed reasonable
      reproducibility for the evaluation of nasal (NV) and epipharyngeal (EV) volume.
      Decongestion with xylometazoline resulted in a 36% enlargement of nasal volume on
      average. The alteration of pharyngeal soft tissues due to maxillomandibulary
      advancement of 10 mm correlated to an increase of the EV-index of 6 cm3. Acoustic
      rhinometry identifies location and amount of nasal obstruction and in addition
      allows differentiation between obstruction due to mucosal hypertrophy and that
      due to skeletochondral deformity. Changes in the epipharyngeal volume following
      maxillary and mandibular osteotomies can be estimated in comparison with the
      preoperative situation.

PMID- 7525654
TI  - Protein C inhibitor is expressed in tubular cells of human kidney.
AB  - Protein C inhibitor (PCI) is a serpin that inhibits a number of proteases. PCI is
      found in urine and binds to kidney epithelial cells. To determine if kidney is a
      source of PCI, cDNA was produced from human kidney total RNA. Sequencing and
      restriction mapping showed identity between kidney and liver PCI cDNA sequences.
      Similar cDNAs were obtained from rhesus monkey kidney and liver RNAs. Conditioned
      medium from the rhesus monkey kidney cell line CCL7.1 was analyzed on
      immunoblots, showing a 57,000-D protein band that comigrated with human plasma
      PCI. Immunohistochemical staining and in situ hybridization of human kidney
      tissue sections showed that kidney PCI antigen and RNA were confined to tubular
      cells. The findings are consistent with the idea that PCI is synthesized and
      localized in kidney tissue where it may provide protease inhibitory activity and
      suggest that complexes of PCI with urokinase found in human urine may be produced
      locally in the kidney.

PMID- 7525657
TI  - Effects of combination endocrine treatment on normal prostate, prostatic
      intraepithelial neoplasia, and prostatic adenocarcinoma.
AB  - AIMS: To investigate the effect of combination endocrine treatment (CET) or
      luteinising hormone releasing hormone agonist and flutamide on non-neoplastic
      prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma.
      METHODS: The morphology, including the mitotic activity, of 12 radical
      prostatectomies from patients with prostatic adenocarcinoma pretreated for three
      months with CET was evaluated in haematoxylin and eosin stained sections and
      compared with an untreated age and stage matched control group. RESULTS: A
      differential effect on the non-neoplastic prostate was observed. In fact, the
      transition zone of the treated prostate showed simplification of the glandular
      lobules: the ducts and acini were small without undulations of the epithelial
      border and with a prominent basal cell layer. Within the peripheral zone there
      was inconspicuous branching of the ducts and acini which looked dilatated and
      lined by flattened atrophic epithelium. Prostatic intraepithelial neoplasia
      occurred in scattered ducts and acini in the peripheral zone of 10 of the 12
      patients. The epithelial cell lining showed a prominent basal cell layer. A
      certain degree of secretory cell type stratification was always present. However,
      crowding was less evident than in the untreated prostate because of cytoplasmic
      clearing and enlargement as a result of coalescence of vacuoles. The treated
      adenocarcinomas had neoplastic acini which looked small and shrunken, and areas
      of individual infiltrating tumour cells separated by abundant interglandular
      connective tissue. The secretory cells of the nonneoplastic, prostatic
      intraepithelial neoplasia, and prostatic adenocarcinoma lesions had inconspicuous
      nucleoli, nuclear shrinkage, chromatin condensation, and cytoplasmic clearing.
      Apoptotic bodies were easily identifiable in all the cell layers. The lumina were
      rich in macrophages, sloughed secretory cells with degenerative features, and
      apoptotic bodies. Mitoses were not observed in any of the treated non-neoplastic
      prostate, prostatic intraepithelial neoplasia, or prostatic adenocarcinomas,
      whereas the mitotic frequency increased from non-neoplastic prostate through
      prostatic intraepithelial neoplasia up to prostatic adenocarcinomas in the
      untreated specimens. CONCLUSIONS: CET before radical prostatectomy causes
      regressive epithelial changes together with enhanced apoptosis and blocked
      mitotic activity.

PMID- 7525660
TI  - In situ hybridisation for the identification of Helicobacter pylori in paraffin
      wax embedded tissue.
AB  - A method for identifying Helicobacter pylori using a non-isotopic in situ
      hybridisation technique is described. A probe generated by polymerase chain
      reaction (PCR) with primers directed against parts of the Helicobacter pylori
      16SrRNA sequence was used. Paraffin wax embedded gastric biopsy specimens from
      patients with and without gastritis were hybridised with the probe, and the
      method was shown to be sensitive and specific for H pylori.

PMID- 7525661
TI  - Pharmacokinetics of FK506 after intravenous and oral administration in patients
      awaiting renal transplantation.
AB  - The authors examined the safety and pharmacokinetics of FK506, a new hepatically
      metabolized immunosuppressant, after single-dose intravenous (i.v.) infusion (20
      micrograms.kg(-1) x 4 hours-1) and oral (80 micrograms/kg) administration in six
      nondialysis patients, aged 27 to 53 years, with chronic renal failure awaiting
      transplantation. A two-period, randomized, crossover study protocol was used with
      blood samples drawn for 72 hours after each dose and a washout period of 4 days.
      Whole-blood FK506 levels were determined using a standard, two-step, nonspecific
      enzyme immunoassay. There were no significant changes in vital signs, EKG, or
      complete laboratory test battery for any patient during the entire study period.
      No side effects were noted after i.v. or oral FK506 dosing. Mean +/- SD
      distribution half life was 0.9 +/- 0.2 hours, elimination half life (t1/2 beta)
      33 +/- 8 hours, total body clearance (CL) 2.4 +/- 1.1 L/hour, and bioavailability
      14 +/- 12%. There was no significant correlation between serum creatinine (Cr)
      and CL (r = 0.36) or between Cr and t1/2 beta (r = -0.30). It was found that
      FK506 is incompletely and erratically absorbed after oral administration and is
      rapidly distributed outside the blood compartment after IV dosing. An extended
      sampling period seems necessary to accurately characterize the slow elimination
      phase of FK506.

PMID- 7525662
TI  - Successful treatment of clozapine-induced agranulocytosis with granulocyte colony
      stimulating factor.

PMID- 7525658
TI  - Comparison of cell adhesion molecule expression in cutaneous leucocytoclastic and
      lymphocytic vasculitis.
AB  - AIMS: To compare the expression of the cell adhesion molecules intercellular
      adhesion molecule-1 (ICAM-1), ELAM-1 (E-selectin), and vascular cell adhesion
      molecule-1 (VCAM-1) in cutaneous leucocytoclastic and lymphocytic vasculitis.
      METHODS: Immunohistochemical analysis was performed on early lesional skin biopsy
      specimens of leucocytoclastic vasculitis (n = 14), lymphocytic vasculitis (n =
      10), non-lesional skin (n = 12), and normal skin (n = 5). A standard
      immunoperoxidase technique was used to detect expression of ICAM-1, E-selectin,
      VCAM-1, and the cell markers CD11a, CD11b, CD11c, von Willebrand factor, CD3,
      CD68, and neutrophil elastase (NP57). RESULTS: Basal keratinocyte intercellular
      adhesion molecule-1 was expressed in eight (80%) cases of lymphocytic and in only
      one (7%) case of leucocytoclastic vasculitis, and not in non-lesional skin or
      control biopsy specimens from normal subjects. E-selectin was expressed on
      vascular endothelium in eight (57%) cases of leucocytoclastic and in seven (70%)
      cases of lymphocytic vasculitis. Endothelial vascular cell adhesion molecule-1
      expression was seen in three (21%) biopsy specimens of leucocytoclastic and five
      (50%) of lymphocytic vasculitis. There were increased numbers of cells in the
      dermal infiltrate stained for NP57, CD11b, and CD11c in leucocytoclastic compared
      with lymphocytic vasculitis (p < 0.001, p = 0.013, p = 0.009, respectively);
      immunoreactive positive cells for CD3 and CD11a were increased in lymphocytic
      compared with leucocytoclastic vasculitis (p < 0.001, p = 0.011, respectively).
      CONCLUSIONS: These observations indicate that upregulation of adhesion molecule
      expression occurs in both leucocytoclastic and lymphocytic vasculitis. The
      different patterns of adhesion molecule expression in the two groups of
      vasculitis may reflect differences in the local release of cytokines. In
      particular, detection of intercellular adhesion molecule-1 expression by
      keratinocytes in lymphocytic vasculitis is consistent with an active role for
      mediators derived from T lymphocytes in the pathogenesis of the lesion.

PMID- 7525659
TI  - Serum laminin in malaria.
AB  - AIM: To determine serum laminin concentrations in patients with uncomplicated
      Plasmodium falciparum malaria. METHODS: An enzyme linked immunosorbent assay
      (ELISA) was used to determine serum laminin concentrations in 54 patients with
      acute uncomplicated P falciparum malaria during and after treatment, and in 17
      control subjects in Bangkok, Thailand. RESULTS: Raised concentrations of soluble
      laminin were observed in patients (mean (SD) concentration 628 (225) ng/ml),
      compared with normal controls (490 (116) ng/ml), during the acute phase of the
      disease. During treatment, serum laminin concentrations decreased and returned to
      normal within three days. Serum laminin concentrations were correlated with
      parasite counts before treatment, and with the serum concentration of soluble
      intercellular adhesion molecule-1 (ICAM-1), soluble E-selectin, and soluble
      tumour necrosis factor receptor at 55 kilodaltons. CONCLUSIONS: These findings
      are compatible with an increased production or release of laminin in P falciparum
      malaria, which could indicate a role for the subendothelial basement membrane in
      the pathogenesis of the disease.

PMID- 7525663
TI  - Neuroactive substances in the developing dorsomedial telencephalon of the pigeon
      (Columba livia): differential distribution and time course of maturation.
AB  - The avian hippocampal formation has previously been shown to contain many of the
      same neurotransmitters and related enzymes that are found in mammals. In order to
      determine whether the relatively delayed development of the mammalian hippocampus
      is typical of other vertebrates, we investigated the maturation of a variety of
      neuroactive substances in the hippocampal formation of the homing pigeon. The
      distribution of two transmitter-related enzymes, choline acetyltransferase (ChAT)
      and tyrosine hydroxylase (TH), the neurotransmitter GABA, and four neuropeptides
      (substance P, enkephalin, neuropeptide Y, and somatostatin) was studied by
      immunohistochemistry in the developing hippocampal complex. The pattern and/or
      the time course of changes in the distribution of immunoreactivity varied among
      the different neuroactive substances examined. Immunoreactivity to ChAT and TH
      was found exclusively in fibers and terminal-like processes, whereas GABA and
      peptide immunoreactivity was seen in cells and neuropil. Quantitative differences
      in the density, number, and size of stained cells were assessed by a computer
      assisted image analyzer. For the majority of the substances, developmental
      patterns in the distribution of immunoreactivity differ between the hippocampus
      proper and the area parahippocampalis, the two major areas that together make up
      the avian hippocampal complex. The adult pattern of immunoreactivity was
      generally attained by 3 weeks after hatching. For many of the neuroactive
      substances found in cell bodies, there was a gradual decrease in the density of
      immunoreactive cells with a concomitant increase in the density of immunoreactive
      neuropil. The actual number of stained cells usually increased to a peak at 9
      days posthatching and then declined until 3 weeks posthatching, when the adult
      value was reached. These results are discussed in relation to the advantages that
      the pigeon hippocampal complex may provide in the study of developmental
      processes. Parallels with the distribution of the same neuroactive substances in
      the mammalian hippocampus are used to suggest possible functional similarities
      between the avian and mammalian hippocampal regions.

PMID- 7525664
TI  - Amino acid immunocytochemistry of primary afferent terminals in the rat dorsal
      horn.
AB  - We combined transganglionic tracing methods with postembedding electron
      microscopic immunocytochemistry to determine whether identified primary afferent
      fibers terminating in spinal laminae I-IV may use glutamate and aspartate as
      neurotransmitters. Sciatic injections of wheat-germ agglutinin conjugated to
      horseradish peroxidase labeled fine afferent fibers with terminals in laminae I
      II of the lumbar spinal cord, whereas injections of the B subunit of cholera
      toxin conjugated to horseradish peroxidase labeled primary afferent terminals in
      deeper laminae. Many labeled primary afferent terminals in superficial laminae
      were involved in glomerular synaptic arrangements; others established
      nonglomerular contacts. Most glomerular arrangements were clearly immunopositive
      for glutamate, compared with dendrites, astrocytes, or terminals immunopositive
      for gamma-aminobutyric acid (GABA). The degree of enrichment varied in labeled
      terminals of different morphological types. Aspartate was enriched, though to a
      lesser degree than glutamate, in labeled central terminals of glomeruli in
      superficial laminae. Labeled primary afferent terminals in laminae III-IV were
      immunopositive for glutamate, though at lower levels than glomerular terminals in
      superficial laminae. Aspartate was not enriched in these terminals compared with
      dendrites, glia, and GABA-positive terminals. These results support a
      neurotransmitter role for glutamate in primary afferents to the dorsal horn.
      Quantitative differences in the content of glutamate in identified primary
      afferent terminals may be related to functional differences. Enrichment of
      aspartate in terminals in superficial but not deep laminae is compatible with a
      role for this amino acid in sustained, NMDA-mediated phenomena characteristic of
      activity in fine caliber afferents.

PMID- 7525665
TI  - Double immunoenzymatic labelling of intermediate filaments in bovine urinary
      bladder tumours.
AB  - Double immunoenzymatic labelling made possible the simultaneous staining of two
      antigens with a mixture of polyclonal and monoclonal commercial antibodies.
      Immunocharacterization of intermediate filament proteins was found to be an
      accurate indicator of histogenesis in urinary bladder tumours of cattle.

PMID- 7525666
TI  - Malignant melanoma with clinical and histologic features of Merkel cell
      carcinoma.
AB  - We describe a patient with malignant melanoma that resembled a Merkel cell
      carcinoma both clinically and histologically. Immunohistochemical studies showed
      focally positive staining with S-100 protein and strongly positive staining with
      HMB-45. Ultrastructural study confirmed the diagnosis by demonstrating
      premelanosomes and melanosomes. Although the tumor appeared to be clinically
      unimpressive, it was a deep melanoma with a Breslow level of 3.8 mm that
      necessitated aggressive treatment. Small cell melanoma must be considered in the
      differential diagnosis of small cell tumors, which also includes lymphoma,
      eccrine carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. The
      diagnosis of amelanotic melanoma, including the small cell variant, may require
      electron microscopic studies.

PMID- 7525668
TI  - Horizons in pharmacologic intervention in allergic contact dermatitis.
AB  - The treatment of allergic contact dermatitis remains a major challenge. Current
      management strategies consist of elimination of the allergen when possible and
      therapy for symptoms with topical or systemic corticosteroids. With increasing
      exposure of the human skin to environmental antigens and haptens, more selective
      treatment options are needed. Advances in the elucidation of the skin immune
      system and of the cellular and molecular events in immunologic processes may
      allow targeted methods of controlling delayed hypersensitivity reactions. This
      review focuses on mechanisms of established therapeutic agents and new
      developments, such as FK 506 (tacrolimus), pentoxifylline, and vitamin D3
      derivative, for suppression of any phase of allergic contact dermatitis.

PMID- 7525669
TI  - QBEND/10 (anti-CD34 antibody) in external root sheath cells and follicular
      tumors.
AB  - The human hematopoietic progenitor cell antigen (CD34) is a cell surface protein
      expressed by human hematopoietic progenitor cells, vascular endothelium, and many
      mesenchymal tumors. Sections from six samples of normal skin and from 41
      epithelial tumors of the skin were studied. Immunostaining of epithelial cells
      from the external root sheath below the attachment of the arrector pili muscle
      and above the matrix cells was noted in normal samples. Tumors derived from or
      differentiated toward cells of the outer sheath, especially trichilemmomas, were
      immunostained with QBEND/10 (anti-CD34 antibody), whereas other epithelial tumors
      studied were negative. CD34 could serve as a marker of outer sheath cell
      derivation and may well be of value in the distinction between trichilemmomas and
      other lesions with similar histopathological features.

PMID- 7525670
TI  - CD44 expression in alopecia areata and androgenetic alopecia.
AB  - CD44 is a widely distributed cell surface protein thought to be involved in
      multiple steps of normal immune cell function, including T-cell activation, and
      in cellular adhesion where it mediates cell attachment to hyaluronate. In normal
      skin, CD44 is found by immunohistochemical means to be primarily in eccrine coil
      cells. In this study, we have looked at the expression of CD44 in normal scalp
      and in two different hair disorders, androgenetic alopecia and alopecia areata.
      In normal scalp and androgenetic alopecia, CD44 was found in its normal
      distribution in eccrine coil cells. In scalp of 30 patients with alopecia areata,
      there was no expression of this glycoprotein. Patients were also assessed pre and
      post treatment for their alopecia areata, and even though they had no significant
      hair regrowth, 2 patients regained expression of CD44, indicating a variable
      expression of this protein in the alopecia areata disease process. The absence of
      CD44 expression in alopecia areata-affected scalp may give further information
      regarding the pathogenesis of this disease.

PMID- 7525671
TI  - Mast cells in angiolipomas and hemangiomas of human skin: are they important for
      angiogenesis?
AB  - To characterize the potential role of mast cells (MC) in angiogenesis, this study
      tests the hypothesis that MC may be more abundant in angiolipomas than in classic
      lipomas. MC counts were compared in 13 subcutaneous angiolipomas and 15
      subcutaneous classic lipomas stained with Giemsa. Angiolipomas had ten times as
      many MC as did classic lipomas (25.34 +/- 2.83 versus 2.41 +/- 0.37 per mm2, mean
      +/- SE). To clarify whether this difference was primary (angiogenic activity) or
      secondary to the increased vascularity, MC were counted in 8 longstanding
      cutaneous capillary hemangiomas versus 13 cutaneous capillary hemangiomas of
      recent onset (pyogenic granulomas). If MC were mediating primary angiogenesis,
      one would expect them to be present in greater numbers in early than in late
      hemangiomas. To the contrary, however, long-standing hemangiomas were found to
      have significantly more MC than had those of recent onset (52.48 +/- 14.99 versus
      6.59 +/- 3.37 per mm2, mean +/- SE). These results suggest that MC may not play
      an essential, early role in the proliferation of blood vessels in angiolipomas
      and hemangiomas, but rather may be related to maturation of blood vessels in
      these tumors.

PMID- 7525672
TI  - Metastatic prostatic carcinoma histologically mimicking malignant melanoma.
AB  - Prostatic carcinoma rarely metastasizes to the skin. We describe a case in which
      inguinal metastasis occurred. Histologically, the tumor was composed of pale
      staining cells which had pronounced epidermotropism, producing a pagetoid pattern
      mimicking that seen in malignant melanoma. The diagnosis was confirmed by
      demonstrating prostatic specific antigen in tumor cells.

PMID- 7525667
TI  - Cutaneous metastases of pancreatic carcinoma with unusual clinical features.
AB  - Cutaneous metastases from pancreatic carcinoma are uncommon. Eight cases have
      been described in the literature. The metastases display some common features
      such as umbilical nodules and the histologic pattern of adenocarcinoma. Our
      patient had erythematous infiltrated plaques in the left axilla and on the upper
      portion of the chest. A skin biopsy specimen disclosed many poorly differentiated
      atypical cells throughout the dermis. The diagnosis was confirmed by positive
      immunohistochemical staining for carbohydrate antigen 19-9.

PMID- 7525673
TI  - Expression of insulin-like growth factor-I in cows at different stages of
      lactation and in late lactation cows treated with somatotropin.
AB  - Relative amounts of IGF-I mRNA were measured in livers of Holstein cows at
      different stages of lactation (6 early, 6 mid, 6 late lactation, 6 dry) and 6
      late lactation cows treated with bST for 1 wk. Milk yield was greater for early
      lactation cows than for mid and late lactation controls. All cows except those in
      early lactation were in positive energy balance. Serum IGF-I increased as
      lactation progressed and was greatest during the dry period. Liver IGF-I mRNA was
      less in cows in early than in late lactation but greater in lactating than in dry
      cows. Treatment with bST increased milk yield and concentrations of serum IGF-I,
      hepatic IGF-I mRNA, and serum IGF-binding protein-3, decreased concentration of
      serum IGF-binding protein-2, and did not alter abundance of mammary IGF-I mRNA.
      These parallel changes in serum IGF-I and hepatic IGF-I mRNA suggest that
      exogenous bST increases IGF-I synthesis in liver of cows during late lactation
      and that IGF-I synthesis is depressed during early lactation when cows are in
      negative energy balance. We conclude that IGF-I may play an endocrine role in
      mediating galactopoietic effects of exogenous bST during late lactation. However,
      the role of IGF-I during early lactation remains unclear.

PMID- 7525674
TI  - Killing of cariogenic bacteria by light from a gallium aluminium arsenide diode
      laser.
AB  - Suspensions of Streptococcus mutans, S. sobrinus, Lactobacillus casei and
      Actinomyces viscosus were exposed to light from a gallium aluminium arsenide
      laser in the presence of aluminium disulphonated phthalocyanine and the numbers
      of survivors determined. Exposure to the laser light in the absence of the dye,
      or the dye in the absence of the laser light, had no significant effect on the
      viability of the organisms. However, a light-dose-related decrease in the viable
      count of all four target organisms was found on exposure to the laser light in
      the presence of the dye. The kills attributable to lethal photosensitization
      amounted to approximately 10(6) CFU in the case of each organisms. As appreciable
      kills were achieved within clinically convenient exposure times (30-90 s), these
      results imply that lethal photosensitization may be a useful technique for
      eliminating bacteria from carious lesions prior to restoration.

PMID- 7525675
TI  - Significance of thermal cycling in microleakage analysis of root restorations.
AB  - Root surface cavities prepared in extracted premolars were restored with a
      selection of restorative materials. Prior to eosin dye immersion, one group of
      teeth was kept at constant temperature whilst another group underwent thermal
      cycling. The teeth were sectioned transversely through the restorations and an
      assessment of the degree of microleakage was used to compare the sealing ability
      of the selected materials. Eosin dye was able to discriminate more effectively
      between the microleakage behaviour of the restorative materials when samples were
      kept at a constant temperature.

PMID- 7525676
TI  - Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony
      stimulating factor (GM-CSF) in Behcet's disease.
AB  - Increases in the number and activity of peripheral polymorphonuclear neutrophils
      (PMNs) is often found in Behcet's disease (BD), indicating that PMN may play an
      important role in the pathogenesis of this disorder. It has recently been
      reported that G-CSF and GM-CSF, a family of hematopoietic growth factors, enhance
      PMN activity. To explore the role of these two CSFs in BD, we first examined the
      chemotactic response of PMNs to these CSFs by performing a polarization assay.
      PMN response to G-CSF in BD patients was lower than that in controls, while PMN
      response to GM-CSF was similar in patients and controls. However, PMNs from BD
      patients showed an enhanced chemotactic response to N-formyl-L-methionyl-leucyl
      phenylalanine. Thus, it is speculated that the PMNs of the patients might have
      already been activated in vivo by G-CSF and thus could not respond further to
      this agent in vitro. We examined G-CSF and GM-CSF mRNA expressions in peripheral
      mononuclear cells stimulated with LPS, PMA, and Con A by Northern hybridization.
      G-CSF mRNA expression levels in BD patients were higher than in the controls,
      while GM-CSF mRNA expression levels were lower than in the controls. We also
      examined the serum levels of the two CSFs by ELISA and EIA. However, all levels
      of the two CSFs in both patients and controls were not detectable, except in the
      case of one BD patient in the active stage of the disease, who showed high levels
      of G-CSF, but not of GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525677
TI  - An immunohistochemical study of sebaceous carcinoma with anti-keratin monoclonal
      antibodies: comparison with other skin cancers.
AB  - Formalin-fixed and paraffin-embedded tissue specimens of six cases of extraocular
      sebaceous carcinoma were studied immunohistochemically with eight anti-keratin
      monoclonal antibodies, 34 beta B4, 35 beta H11, Ks13.1, Ks19.1, PKK1, LP34, KL1
      and AE1. The staining patterns of sebaceous carcinoma were compared with those of
      normal sebaceous glands and other skin cancers which should be distinguished from
      sebaceous carcinoma histopathologically. The other skin cancers compared were
      eccrine porocarcinoma, malignant clear cell hidradenoma, extramammary Paget's
      disease with underlying adenocarcinoma, malignant trichilemmoma, and squamous
      cell carcinoma. Most cases of sebaceous carcinoma were stained with 35 beta H11,
      Ks19.1, LP34, KL1 and AE1, while normal sebaceous glands were positive only with
      35 beta H11, LP34, KL1 and AE1. By immunostaining, sebaceous carcinoma was
      distinguishable from extramammary Paget's disease with underlying adenocarcinoma,
      squamous cell carcinoma, malignant trichilemmoma, and eccrine porocarcinoma, but
      was not clearly distinguishable from malignant clear cell hidradenoma. These
      findings demonstrate that sebaceous carcinoma shows positive reactions with
      antibodies to simple epithelial keratin, probably as a result of neoplastic
      transformation, and that immunohistochemical examination using anti-keratin
      monoclonal antibodies is useful in distinguishing sebaceous carcinoma from
      several other skin cancers.

PMID- 7525679
TI  - Passive transfer of cutaneous mosquito-bite hypersensitivity by IgE anti-saliva
      antibodies.
AB  - BACKGROUND: Mosquito bites frequently cause cutaneous wheal and flare reactions,
      and recent immunoblotting studies have shown specific anti-saliva IgE antibodies
      in many persons who have such reactions. OBJECTIVE: The study was designed to
      show that human serum containing mosquito saliva-specific IgE antibodies can
      produce histamine release in vitro and whealing in vivo. METHODS: Two mosquito
      bite-tolerant subjects had bite challenges and Prausnitz-Kustner tests with
      heated and unheated serum from one patient with Aedes mosquito allergy.
      Immunoblotting and basophil histamine release tests were performed with the
      patient's and subjects' sera. RESULTS: Both mosquito bite-tolerant subjects had
      positive Prausnitz-Kustner reactions, which indicated a successful transfer of
      cutaneous mosquito hypersensitivity. The ordinary and passive basophil histamine
      release tests also produced positive results with Aedes communis antigens.
      CONCLUSION: The results of the Prausnitz-Kustner test, immunoblotting, and
      basophil histamine release tests are consistent with the hypothesis that mosquito
      bite whealing is mediated by specific anti-saliva IgE antibodies.

PMID- 7525678
TI  - Human FcERI-IgG and humanized anti-IgE monoclonal antibody MaE11 block passive
      sensitization of human and rhesus monkey lung.
AB  - IgE antibodies are thought to play an important role in the induction of allergic
      inflammation of the bronchi. In this study we assessed the capacity of two
      inhibitors, FcERI-IgG, an immunoadhesin made up of the alpha chain of the high
      affinity IgE receptor joined to a truncated IgG heavy chain, and MaE11, a
      humanized murine anti-human IgE antibody, to prevent allergen sensitization. Lung
      parenchyma strips from rhesus monkeys and human beings were passively sensitized
      for 20 hours with serum from a ragweed-sensitive patient in the presence of 0, 1
      , 5-, or 10-fold concentrations of the inhibitors relative to IgE. The
      parenchymal strips were then suspended in a superfusion apparatus for measurement
      of isometric tone and collection of superfusate for histamine analysis in
      response to challenge with antigen E (AgE). Nonsensitized tissues did not react
      to AgE challenge, whereas AgE challenge of passively sensitized tissues resulted
      in a time-dependent parenchymal contraction and histamine release. Both FcERI-IgG
      and MaE11 completely abolished the AgE-induced contraction and histamine release
      in a dose-dependent manner. In addition, passively sensitized lung tissues failed
      to respond to direct challenge with either FcERI-IgG or MaE11. The results of
      this study suggest that FcERI-IgG and MaE11 may have important immunotherapeutic
      benefit for the amelioration of IgE-mediated diseases.

PMID- 7525680
TI  - Regulation of allergen-specific immune responses by CD4+ CD45R+ cells in patients
      with allergic contact dermatitis.
AB  - Circulating T lymphocytes from 20 patients with an immediate patch test reaction
      were tested for proliferative responses in vitro to contact allergens during both
      immediate and delayed skin reactions. T lymphocytes collected during the
      immediate patch test reaction responded specifically in the challenge allergens
      in the presence of autologous monocytes. Subset analysis revealed that the
      proliferation pattern was dominated by the CD4+ CD29+ T-cell subpopulation,
      whereas CD8+ or CD4+ CD45R+ cells did not respond. A similar pattern in T-cell
      subset proliferation was observed when cells were collected during a positive
      delayed skin reaction. In contrast, in the case of a negative delayed skin
      reaction, proliferative responses of lymphocytes to the specific allergens were
      dominated by CD45+ cells. The latter T-lymphocyte subset could greatly suppress
      in an allergen-specific manner the proliferation of CD29+ autologous cells. The
      in vitro allergen-specific proliferation of CD29+ or CD45R+ cells was restricted
      by the major histocompatibility complex class II (HLA-DR) gene products. It is
      suggested that allergen-specific immune responses take place in the induction and
      evolution of an immediate patch test reaction into a delayed one.

PMID- 7525681
TI  - School-based nutrition services positively affect children with special health
      care needs and their families.

PMID- 7525684
TI  - A simple and inexpensive chromatographic method for the purification of gamma
      globulin from human serum.
AB  - Inexpensive cation- and anion-exchangers based on continuous polymer beds were
      prepared directly in a plastic syringe. These beds are unique in the sense that
      they are synthesized by a very simple and cost-effective procedure; for instance,
      no preparation of beads is required as in conventional methods. Highly purified
      gamma-globulin could be prepared easily by step-wise elution accomplished by
      forcing buffers of increasing salt concentration through the column with the aid
      of the plunger.

PMID- 7525683
TI  - The protein effect on determination of DNA with Hoechst 33258.
AB  - The present study was designed to afford a critical review of the effect of
      proteins on the Hoechst 33258 method for determination of DNA of crude
      homogenates. A considerable effect of proteins on the fluorescence was observed
      when the concentration exceeded 100 micrograms BSA equivalent protein. Below that
      value, practically no effect of proteins was noted. We used proteinase K to
      remove the proteins, but dilution of homogenates could be used as well. Moreover,
      we found that the concentration of the fluorochrome should be between 1 microgram
      and 2 micrograms when microgram levels DNA are to be determined.

PMID- 7525682
TI  - Local treatment of pressure sores in the elderly: amino acid copolymer membrane
      versus hydrocolloid dressing.
AB  - OBJECTIVE: To compare the clinical effectiveness and wound management properties
      of a copolymer membrane, Inerpan (Synthelabo), and a hydrocolloid dressing,
      Comfeel (Coloplast), in the treatment of decubitus ulcers in the elderly. DESIGN:
      Open, randomized, multicentric French study, with two parallel groups of
      patients. PATIENTS: 168 in-patients aged more 65 years (mean age: 82 years)
      suffering from grade II to grade IV (in the Shea classification) pressure sores.
      TRIAL PERIOD: Either 8 weeks or until the ulcer healed, whichever occurred first.
      MEASUREMENTS: In addition to a complete physical examination, patients were
      evaluated at baseline for nutritional status and risk factors. The wounds were
      described, their depth scored, and the areas traced at Weeks 0, 1, 2, 4, 6, and
      8. The number of dressings used was recorded. RESULTS: Thirty-one Inerpan-treated
      patients and 23 Comfeel-treated patients achieved healing (P = 0.089), with
      respective median healing times of 32 and 38 days. Healing times were compared
      using survival curves (in the whole population) adjusted for ulcer depth effect
      and showed a significant difference in favor of Inerpan (P = 0.044 and 0.014).
      Progress of healing (percentage of ulcer healed) was calculated in the two
      groups. Clinically assessed the treatment performance scored at the completion of
      the study showed better results with Inerpan (P < 0.05). Both groups were similar
      in terms of granulation/exudation scores, surrounding skin, and ease of care.
      CONCLUSION: It is concluded that Inerpan is easy to use, safeguards the healing
      process, and is of particular value in the management of pressure sores.

PMID- 7525685
TI  - Trigeminal sensory innervation on perforators of the circle of Willis in rabbits
      by wheat germ agglutinin-conjugated horseradish peroxidase anterograde tracing.
AB  - Distribution patterns of sensory innervation from the trigeminal ganglion to the
      perforators of the circle of Willis in rabbits were investigated by wheat germ
      agglutinin-conjugated horseradish peroxidase (WGA-HRP) anterograde tracing.
      Twenty Japanese white rabbits were anesthetized by inhaling 1% halothane. Using a
      microsurgical technique, 4 microliters of 2% WGA-HRP in 1 M KCl solution, colored
      with brilliant blue, was micro-injected into the medial part of the left
      trigeminal ganglion in 14 animals with a pressure injection system. Another six
      served as controls to exclude the possibility of labeling non-trigeminal axons.
      Forty-eight hours later, the perforators in the cisternal and intracerebral
      segments along with their parent arteries were dissected from the brain according
      to Dacey's dissecting technique after transcardial perfusion, reacted with the
      3,3',5,5'-tetramethyl benzidine method of Mesulam. The results revealed that
      sensory nerves on the perforators of the circle of Willis were less densely
      innervated than those on their parent arteries due to the difference in diameter.
      The posteromedial perforating arteries arising from the P1 segment of the
      posterior cerebral artery to the tegmentum, posteroventral thalamus and posterior
      hypothalamus were more prominently and consistently innervated than other
      perforators. The sensory fibers were seen on the cisternal segment of the
      perforating arteries. A parallel or twisted pattern was found in the perforators
      less than 100 microns in diameter, while a meshwork pattern was visualized in the
      proximal part of some bigger ones. Fine sensory fibers could be traced on the
      perforators as small as 40 microns in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525688
TI  - Distribution and pathway of the cerebrovascular nerve fibers from the otic
      ganglion in the rat: anterograde tracing study.
AB  - The distribution and pathway of cerebrovascular nerve fibers from the otic
      ganglion were studied by an anterograde tracing technique in the rat. Wheat germ
      agglutinin-horseradish peroxidase was injected as an anterograde axonal tracer
      into the otic ganglion on one side. Forty-eight hours later, the animals were
      killed and specimens were reacted with tetramethylbenzidine. Wheat germ
      agglutinin-horseradish peroxidase positive fine nerve fibers were observed in the
      circle of Willis and its branches, i.e., anterior cerebral artery, middle
      cerebral artery, internal ethmoidal artery and posterior cerebral artery, while
      no positive fiber could be detected in the vertebrobasilar artery. A positive
      reaction with tetramethylbenzidine was also observed in the lesser superficial
      petrosal nerve, the greater superficial petrosal nerve, the vidian nerve, the
      greater deep petrosal nerve, the internal carotid ganglion and the trigeminal
      ganglion. The sphenopalatine ganglion, however, failed to reveal any positive
      neurons or nerve fibers. It is concluded that the cerebrovascular nerve fibers
      originating from the otic ganglion run along the lesser superficial petrosal
      nerve to join the greater superficial petrosal nerve. They then reach the greater
      deep petrosal nerve and ascend along the internal carotid artery to distribute
      themselves to the cerebral blood vessels. This study demonstrated, for the first
      time, that the otic ganglion innervates the cerebral vessels and elucidated the
      pathway from the otic ganglion to the cerebral vessels directly by means of an
      anterograde axonal tracing technique.

PMID- 7525687
TI  - Expression of nitric oxide synthase immunoreactivity by interstitial cells of the
      canine proximal colon.
AB  - A subpopulation of interstitial cells (ICs) are interposed between nerve
      terminals and smooth muscle cells in the gastrointestinal tract and may
      participate in neuromuscular transmission. These cells appear to be targets for
      NO released from enteric inhibitory nerves and respond to exogenous NO with: (i)
      an elevation in cGMP levels; (ii) an increase in intracellular Ca2+; (iii) and
      release of a diffusible substance that has tentatively been identified as NO. For
      the latter to be possible, ICs must express a constitutive isoform of NOS. This
      study characterized the expression of NOS-like immunoreactivity (NOS-LI) in ICs
      of the canine colon using 3 antibodies raised against the 2 known constitutive
      forms of NOS (i.e., neural (nNOS) and endothelial (eNOS) isoforms). Antibodies
      raised against cNOS and an antibody raised against rat cerebellar nNOS labeled
      ICs along the submucosal surface of the circular muscle layer (IC-SM), along the
      surface of septa that separate the circular muscle into fiber bundles (IC-SM),
      and in the myenteric region between the circular and longitudinal muscle layers
      (IC-MY). Another antibody raised against rat cerebellar nNOS failed to label ICs.
      Cultured IC-SM also expressed NOS-LI, suggesting that this feature of the IC
      phenotype survives culture conditions. Arteriolar endothelial cells in the canine
      colon were labeled with the same 2 antibodies that labeled ICs, suggesting there
      are significant structural similarities between NO synthases in ICs and
      endothelial cells. The data suggest that IC-SM and IC-MY express a constitutive
      form of NOS. Synthesis of NO by ICs may influence electrical rhythmicity and may
      serve to amplify and even propagate enteric inhibitory neurotransmission.

PMID- 7525686
TI  - Patterns of neuronal colocalisation of tyrosine hydroxylase, neuropeptide Y,
      vasoactive intestinal polypeptide, calcitonin gene-related peptide and substance
      P in human ureter.
AB  - The patterns of colocalisation of neuropeptides, tyrosine hydroxylase (TH), and
      protein gene product 9.5 (PGP), were studied in nerve fibres supplying the upper
      and lower human ureter using a double labelling immunofluorescence technique. The
      majority (85%-95%) of nerve fibres within the ureter contained neuropeptide Y
      like immunoreactivity (NPY-LIR), in combination with other peptides.
      Approximately 52%-63% of the total ureteral innervation was made up of NPY-LIR
      fibres also expressing TH-LIR, while 21%-42% of fibres contained NPY-LIR in
      combination with vasoactive intestinal polypeptide (VIP)-LIR. These two
      immunochemically defined classes did not overlap, since TH- and VIP-LIR were
      never present within the same nerve fibre. Other minor populations of neurones
      included those containing calcitonin gene-related peptide (CGRP)-LIR in
      combination with substance P (SP)-LIR (4%-17%) and those without SP (5%). Rare
      coexistences were also noted between CGRP- and VIP-LIR (1%-2%), CGRP- and NPY-LIR
      (< or = 1%), and CGRP- and TH-LIR (< 1%). Regional differences in innervation
      were found. There were fewer of each class of nerve fibres in the upper ureter
      compared to the lower ureter. In addition, the proportion of VIP/NPY-LIR fibres
      of the total innervation was less in the upper ureter, where they were very
      sparse. Differences in the distribution to various tissue targets were also
      observed. In the lower ureter, TH/NPY-LIR fibres were localised predominantly to
      the outer muscle fascicles and adventitia, while VIP/NPY immunoreactive nerves
      supplied the submucosa and inner smooth muscle fascicles. Both of these
      populations were also found around blood vessels. A population of presumptive
      sensory fibres expressing CGRP/SP-LIR were typically present immediately beneath
      the urinary epithelium and around blood vessels, and only very rarely within
      muscle fascicles. The finding that TH/NPY- and VIP/NPY-LIR fibres innervate
      different layers of the ureter raises the possibility that the muscle layers of
      the ureter may be independently controlled.

PMID- 7525691
TI  - Scanning electron microscopic findings in Whipple's disease.

PMID- 7525690
TI  - Utilization of a fos-lacZ plasmid to investigate the activation of c-fos during
      cellular senescence and okadaic acid-induced apoptosis.
AB  - C-fos is an immediate-early gene that is induced by external stimuli and is
      possibly involved in initiation of DNA synthesis by such stimuli. In these
      studies, we used the murine c-fos promoter coupled to a lacZ reporter gene to
      study fos induction in senescent and quiescent cells. In transfected, quiescent,
      immortal Syrian hamster embryo (SHE) cells (10W), serum stimulation induced the
      expression of the fos construct to the same extent that DNA synthesis was
      stimulated. In contrast, in transfected normal cells that have a finite life
      span, we observed that the cells failed to display upregulation of fos-lacZ in
      response to serum in individual cells as they senesced. High doses of the
      phosphatase inhibitor okadaic acid (160-1000 nM) also induced fos-lacZ expression
      in quiescent immortal cells; however, induction of DNA synthesis and expression
      of fos-lacZ were not coordinately induced as a function of okadaic acid
      concentration. Low concentrations of okadaic acid (0.16 nM) induced DNA synthesis
      but not fos-lacZ expression, indicating that induction of DNA synthesis by
      phosphatase inhibitors may bypass, at least quantitatively, the requirement for c
      fos induction. At the levels of okadaic acid that induced fos-lacZ expression,
      cell death, rather than DNA synthesis, was observed. The cells died by apoptosis,
      thereby implicating a signaling pathway that includes c-fos induction in this
      process.

PMID- 7525693
TI  - Analysis of hepatitis C virus genotypes by a line probe assay and correlation
      with antibody profiles.
AB  - The 5' untranslated regions derived from 54 patients with a chronic hepatitis C
      virus infection were analyzed to determine the (sub)type of hepatitis C virus.
      Labelled polymerase chain reaction products from 5' untranslated region were used
      as probes for reverse hybridization in a line probe assay (Inno-LiPA) and results
      were validated by comparison with direct sequencing data. Five different
      genotypes could be distinguished based on 5' untranslated region sequence
      diversity. Results of typing by line probe assay and direct sequencing were
      similar. Antibody responses against core, NS-3, NS-4 and NS-5 epitopes were
      detected by RIBA-4 and Inno-LIA HCVAb II confirmatory assays. There was no
      consistent correlation between genotype and anti-HCV responses, although types 2,
      3 and 4 hepatitis C virus isolates show poor reactivity with NS-4 ep!%"pes.

PMID- 7525692
TI  - IgG and IgM core antibodies and viral replication in hepatitis C virus carriers.
AB  - We studied IgG and IgM antibodies to hepatitis C virus core protein (anti
      HCVcore) in relation to serum virus RNA levels in 71 hepatitis C virus carriers.
      Viremic levels ranged from 10(4)-10(9) copies/ml and were high in 34 chronic
      active hepatitis patients compared with 17 asymptomatic carriers and 20 cases of
      chronic persistent hepatitis (p < 0.01). IgG anti-HCVcore was found in 67/71
      (94%), but four asymptomatic carriers with low levels of viremia (10(4)-10(5.5)
      copies/ml) tested negative. IgM anti-HCVcore was found in patients with high
      levels of viremia (10(8)-10(9) copies/ml), and one (6%) asymptomatic carrier and
      nine (26%) chronic active hepatitis patients tested positive. In chronic
      hepatitis patients, viremic levels were significantly higher in cases positive
      for IgM anti-HCVcore than in negative ones (p < 0.01). However, no correlation
      was found between the occurrence of IgM anti-HCVcore and serum aminotransferase
      levels or the histologic activity index. These findings suggest that although IgG
      anti-HCVcore is sensitive, low viremic patients can escape this screening, and
      that the IgM anti-HCVcore is induced in association with high levels of virus
      replication.

PMID- 7525689
TI  - Age-sensitive T cell phenotypes covary in genetically heterogeneous mice and
      predict early death from lymphoma.
AB  - We have assessed several age-sensitive indicators of immune status in young
      (i.e., 6 to 11-month-old) mice of a genetically heterogeneous population to see
      if these varied in parallel and to determine if one or more of the status indices
      predicted life span or cancer incidence. We report that the number of memory
      (i.e., CD44hi) T cells within the CD8 subset is correlated with number of memory
      cells in the CD4 population, and inversely correlated with the number of naive
      (i.e., CD45RBhi) CD4 cells at both 6 and 11 months of age, suggesting that the
      conversion of naive to memory cells may occur at similar rates in both T cell
      subsets. Mice that ranked high in the proportion of memory T cells (within the
      CD4 and CD8 pools) at 6 months of age tended to retain their ranking at 11
      months, suggesting that the pace or extent of memory cell formation may be a
      consistent trait that distinguishes mice at least within a genetically
      heterogeneous population. Mice that at 6 months of age exhibited high levels of
      CD4 or CD8 memory T cells, low levels of naive CD4 cells, or low levels of T
      cells able to proliferate in response to Con A and IL-2 were found to be
      significantly more likely than their littermates to die within the first 18
      months of life. Cases of follicular cell lymphoma, lymphocytic and lymphoblastic
      lymphoma, and hepatic hemangiosarcoma were seen within the group of mice dying at
      early ages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525694
TI  - Hepatitis C virus serotype II responds more favorably to interferon-alpha
      therapy.
AB  - To determine whether serological typing of hepatitis C virus correlated with the
      response to interferon-alpha therapy, hepatitis C virus serotypes were determined
      by subtype-specific antibody to NS4 polypeptide by enzyme-linked immunosorbent
      assay in 55 Japanese patients with chronic active hepatitis C who subsequently
      received recombinant interferon-alpha 2a therapy. Response to interferon-alpha
      was defined as complete and sustained (n = 12), complete response followed by
      relapse (n = 26), and no response (n = 17). There was no difference in the
      clinical biochemical parameters between these patients groups. However, a higher
      proportion (50.0%) of patients with hepatitis C virus serotype II showed complete
      and sustained response to interferon-alpha, compared to serotype I (11.1%, p <
      0.01). These data indicate that this simple hepatitis C virus serotyping assay is
      a useful predictor of response to interferon-alpha therapy in patients with
      chronic hepatitis C virus infection.

PMID- 7525695
TI  - Asymptomatic anti-HCV seropositive subjects include patients with chronic active
      hepatitis and individuals with normal liver: can we distinguish them?

PMID- 7525696
TI  - The sinusoidal efflux of dibromosulfophthalein from rat liver is stimulated by
      albumin, ligandin and fatty acid binding protein but not by other
      dibromosulfophthalein binding proteins.
AB  - Organic anions can be excreted from the liver into the bile or back into the
      general circulation (sinusoidal efflux). It has previously been shown that the
      net sinusoidal efflux rate of dibromosulfophthalein from the perfused liver into
      the perfusate is the result of actual efflux from and reuptake into the liver,
      and can be strongly influenced by the presence of bovine serum albumin in the
      perfusion medium. The present study investigated whether the influence of albumin
      on the net sinusoidal efflux process is albumin-specific or whether other binding
      proteins could have a similar effect on the sinusoidal efflux. Using a single
      pass liver perfusion technique and short-lasting (pulse) protein infusions, the
      stimulatory effect of a wide range of dibromosulfophthalein binding proteins on
      the sinusoidal efflux process were determined. These experiments showed that all
      the serum albumins tested as well as the liver cytosolic binding proteins fatty
      acid binding protein and ligandin (glutathione S-transferase) stimulated this
      process. The other proteins tested, bovine beta lactoglobulin-b, human gamma
      globulin and chicken egg lysozyme showed no stimulatory effect, despite
      relatively high equilibrium binding of dibromosulfophthalein. No clear-cut
      relationship was found between the equilibrium unbound ligand concentration as
      measured in perfusate and the stimulatory effect, suggesting absence of
      equilibrium binding in the sinusoids. Equilibrium binding of
      dibromosulfophthalein to chicken serum albumin and ligandin as well as the
      dissociation rate constants were determined in vitro with rapid filtration
      techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525697
TI  - High prevalence of hepatitis C virus RNA in the supernatant and the
      cryoprecipitate of patients with essential and secondary type II mixed
      cryoglobulinemia.
AB  - Detection of hepatitis C virus RNA by polymerase chain reaction was performed in
      26 patients with type II mixed cryoglobulinemia, and compared with anti-HCV
      antibody detection. The patients were divided into two groups according to
      etiology: 15 had essential type II mixed cryoglobulinemia and 11 had secondary
      type II mixed cryoglobulinemia. In the essential type II mixed cryoglobulinemia
      group, the prevalence of hepatitis C virus RNA detected by polymerase chain
      reaction was 60% in the supernatant and 93% in the cryoprecipitate. In the
      secondary type II mixed cryoglobulinemia group the prevalence of hepatitis C
      virus RNA was 45% in the supernatant and 55% in the cryoprecipitate. The
      differences between the two groups were not statistically significant. In both
      patient groups, detection of hepatitis C virus RNA in the cryoprecipitate was the
      most sensitive test for hepatitis C virus infection. These results suggest that
      hepatitis C virus might be involved in the origin of mixed cryoglobulinemia.

PMID- 7525698
TI  - Nitric oxide in the clinical arena.

PMID- 7525700
TI  - Identification of epitopes of myelin oligodendrocyte glycoprotein for the
      induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice.
AB  - A recombinant protein corresponding to the Ig-like domain of myelin
      oligodendrocyte glycoprotein (MOG) and synthetic 15-mer peptides of the whole MOG
      molecule with eight amino acid overlaps were screened for their ability to induce
      experimental allergic encephalomyelitis (EAE) in Biozzi AB/H (H-2dq1) and SJL (H
      2S) mice. Clinical and histologic evidence of EAE developed after sensitization
      with the recombinant MOG protein in both AB/H and SJL mice. In AB/H mice at least
      three MOG epitopes within residues 1-22, 43-57, and 134-148 induced clinical and
      histologic EAE, whereas only the sequence 92-106 was encephalitogenic in SJL
      mice. Histologically, the inflammatory response in the central nervous system
      consisted of perivascular accumulations of CD5+ T cells and F4/80+
      macrophage/microglia cells equally distributed in the brain and spinal cord. The
      subpial/meningeal infiltration, characteristic of mouse EAE induced with spinal
      cord homogenate, was only observed in cases of severe clinical disease in SJL
      mice in which the cellular infiltrates predominated in the spinal cord. In spite
      of the presence of histologic lesions in AB/H mice immunized with MOG, clinical
      disease either rapidly resolved or was clinically silent. In contrast to
      immunization of SJL mice with recombinant MOG, sensitization to MOG 92-106
      induced severe clinical paralysis. After recovery these animals relapsed and
      exhibited demyelinated lesions. This study is the first to describe
      encephalitogenic epitopes of MOG that induce both clinical and histologic signs
      of EAE in mice. These and previous findings implicating MOG as a target Ag for Ab
      mediated attack in EAE suggest that such autoreactivity to MOG may be significant
      in the development of human demyelinating diseases such as multiple sclerosis.

PMID- 7525701
TI  - Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B.
AB  - The B cell-associated surface molecule CD40 functions to regulate B cell
      responses. Cross-linking CD40 on B cells can lead to homotypic cell adhesion, IL
      6 production, and, in combination with cytokines, to Ig isotype switching.
      Tyrosine kinase activity is increased shortly after engagement of this receptor.
      Little is known about how the very early events induced by CD40 cross-linking
      link to cellular responses. In this study, we demonstrate that nuclear factor
      (NF)-kappa B and NF-kappa B-like transcription factors are activated after cross
      linking CD40 on resting human tonsillar B cells and on B cell lines. The
      activation is rapid and is mediated through a tyrosine kinase-dependent pathway.
      The complexes detected in electrophoretic mobility shift assays contain p50, p65
      (RelA), c-Rel, and most likely other components. By using transient transfection
      assays, we found that cross-linking CD40 supports NF-kappa B-dependent gene
      expression. Our results define the NF-kappa B system as an intermediate event in
      CD40 signaling and suggest that the CD40 pathway can influence the expression of
      B cell-associated genes with NF-kappa B consensus sites.

PMID- 7525699
TI  - Elevated density and altered pharmacologic properties of myocardial calcium
      current of the spontaneously hypertensive rat.
AB  - DESIGN: The membrane current mediated by the L-type calcium channel (ICa) was
      studied for myocytes isolated from the ventricle of 10- to 11-week-old
      spontaneously hypertensive rats (SHR). RESULTS: Compared with age-matched
      normotensive Wistar-Kyoto (WKY) or Sprague-Dawley rats, the amplitude of ICa was
      greater for the SHR. Two observations suggest that the greater ICa of the SHR was
      not due to hypertrophy. First, the similarity of membrane capacitance for these
      three strains of rat indicated lack of hypertrophy. Secondly, the amplitude of
      ICa was also greater for myocytes isolated from the right ventricle of the SHR.
      The ICa of the SHR was more sensitive to drugs known to activate calcium channels
      via phosphorylation. Specifically, extracellular application of 1 mumol/l
      isoprenaline as well as intracellular dialysis with either 1 mmol/l cyclic AMP or
      with 1 mmol/l adenosine 5'-O-3-thiotriphosphate increased the mean ICa of SHR
      myocytes significantly more than that of WKY rat cells. The ICa of SHR myocytes
      was also more sensitive to BAY K 8644 and its enantiomorphs. CONCLUSION: The
      present data suggest that the greater peak amplitude of ICa for SHR myocytes
      relative to that of myocytes of normotensive rats is due to an increase in
      current density and enhancement of channel phosphorylation.

PMID- 7525702
TI  - CD44 triggering enhances human NK cell cytotoxic functions.
AB  - CD44, a major hyaluronate receptor, is involved in a variety of lymphocyte
      functions including lympho-hemopoiesis, adhesion to high endothelial venules or
      the extracellular matrix, and T cell activation. Here we investigated the ability
      of CD44 to affect the cytotoxic functions of human NK cells. Ligation of CD44 by
      selected mAb (J173 and F10442) resulted in a rapid, dose-response-dependent
      enhancement of NK cytotoxic activity against a panel of tumor target cells that
      varied in their sensitivity to NK killing. Neither enhanced killing against NK
      resistant target cells nor CD44 mAb-mediated redirected lysis was not observed.
      CD44 cross-linking also was found to up-regulate CD16-mediated lysis. In an
      attempt to investigate the early biochemical events that occur after CD44
      ligation, we found that optimal cross-linking conditions induce a rapid increase
      of intracellular free calcium levels, which is abrogated by extracellular Ca2+
      chelation. Moreover, enhanced and more sustained Ca2+ rise resulted from CD16 and
      CD44 coengagement. In contrast, no inositol 1,4,5-trisphosphate generation was
      found after optimal CD44 cross-linking. These results suggest that although CD44
      is not capable of delivering a lytic signal in human NK cells, it coactivates
      spontaneous or CD16-mediated NK cytotoxicity. The variation in intracellular free
      calcium may be one of the signals that account for the costimulation of the lytic
      activity.

PMID- 7525706
TI  - Origin of a T cell clone with a mismatched combination of MHC restriction and
      coreceptor expression.
AB  - Although the existence of a large number of CD8+ class II MHC-specific CTLs had
      long been noticed, the origin of such T cells with a discordant combination of
      specificity and phenotype has been a mystery in the positive selection model.
      Recent reports suggesting the independency of the positive selection of T cells
      from coreceptor-mediated signals raised a possibility that they might be the
      progeny of putative transitional, mismatched, single-positive cells appearing
      before positive selection as proposed in the stochastic/selective model. By
      developing transgenic mice carrying TCR alpha and beta chain genes of a CD8+
      class II MHC Ag-specific allogeneic CTL clone QM11, the origin of such T cells
      with mismatched TCR specificity and coreceptor expression was studied. The
      results indicate that QM11 belongs to a conventional CD8+ T cell population whose
      maturation is dependent on a class I (or class I-like) MHC product. Consequently,
      the reactivity of QM11 to I-Ak can be considered to be an accidental cross
      reaction.

PMID- 7525703
TI  - Screening for cytokine messenger ribonucleic acids in purified human decidual
      lymphocyte populations by the reverse-transcriptase polymerase chain reaction.
AB  - At the time of human embryo implantation, large numbers of maternal
      CD56brightCD16- NK cells appear in the uterus. These unusual lymphocytes are
      believed to control the migration and differentiation of highly invasive fetally
      derived trophoblast cells, which infiltrate into the maternal uterus to remodel
      the spiral arteries during the first trimester. One possible mechanism of control
      is by cytokine production. In this study, highly purified (> 99%) populations of
      first trimester decidual CD56brightCD16- NK cells and CD3+ T lymphocytes were
      obtained by using a FACS. These cells were examined by reverse transcriptase PCR
      for their expression of mRNAs for the following cytokines: granulocyte-macrophage
      (GM)-CSF, CSF-1, TNF-alpha, IFN-gamma, TGF-beta 1, leukemia-inhibitory factor
      (LIF), and IL-2. Then, the expression was compared with that of resting PBL. The
      identity of the PCR products was verified by Southern blotting and hybridization
      with cytokine-specific probes. Both decidual CD56brightCD16- NK cells and CD3+ T
      cells were found to express mRNA for CSF-1, TNF-alpha, IFN-gamma TGF-beta 1, and
      LIF, but GM-CSF mRNA was detected only in CD56bright NK cells. IL-2 mRNA was
      detected in only some decidual T cell samples, and then only after at least two
      rounds of amplification. In contrast, peripheral blood CD56brightCD16- NK cells,
      CD56dimCD16+ NK cells, and CD3+ T cells expressed mRNA only for TNF-alpha and TGF
      beta 1, but not for GM-CSF, CSF-1, IFN-gamma, LIF, or IL-2. These results suggest
      that both decidual NK cells and decidual T cells produce a variety of cytokines
      that may be involved in the control of trophoblast migration and differentiation
      during pregnancy.

PMID- 7525705
TI  - Invariant-cognate peptide exchange restores class II dimer stability in HLA-DM
      mutants.
AB  - Class II presentation mutants have mutations in the HLA-DMA or B genes and are
      defective in the presentation of whole exogenous Ags restricted by HLA-DR, -DQ,
      and -DP. The functional defect in Ag presentation is accompanied by an altered
      conformation of cell surface class II molecules and instability of extracted
      class II dimers in SDS-PAGE; the latter can be corrected by incubation of mutant
      cells in an acidic pH in the presence of cognate peptide. Here we investigated
      the basis for correction of class II dimer instability by acid/cognate peptide
      treatment and the extent to which this treatment corrects the class II
      conformational defect in DMB mutants. We found that an acidic pH generates
      peptide binding sites in class II molecules of DMB mutants by eluting invariant
      chain (li)-derived peptides from them. Cognate peptides can then bind to the
      empty binding sites of class II molecules in a pH-independent manner, which
      results in stabilization of class II dimers. Acid/peptide treatment also restores
      the DR polymorphic epitope recognized by mAb 7.3.19.1 but not the DR polymorphic
      epitope recognized by mAb 16.23; low pH gradually destroys the 16.23 epitope in
      nonmutant cells. Mutant 10.24.6, which has a mutation in the DRA coding region
      creating an extra glycosylation site, also has unstable DR dimers whose stability
      is restored by acid/peptide treatment. These results suggest that the primary
      phenotypic defect in both the DMB and 10.24.6 mutants is the abundance of li
      peptides and lack of cognate peptides bound to class II molecules.

PMID- 7525704
TI  - Modulation of signaling via the B cell antigen receptor by CD21, the receptor for
      C3dg and EBV.
AB  - CD21 is the receptor for C3dg and EBV. Several reports have shown that these CD21
      ligands, and certain anti-CD21 mAb, trigger B cell activation, particularly when
      combined with Ag receptor ligation. However, the characteristics, biologic
      functions, and importance of this CD21-signaling pathway are unknown. We have
      used a model we recently developed to study B cell activation induced by complex
      particulate Ag, such as immune complexes and viruses, to begin to examine these
      questions. In the current studies, we incubated purified small resting B cells
      with 100-nm latex beads bearing various combinations of CD21 ligands and mAbs to
      CD19, CD35, and the Ag receptor. CD21, CD19, and CD35 have all been implicated in
      modulating membrane IgM initiated signaling. Beads coated with mAb to the
      C3dg/EBV-binding portion of CD21, but not mAb to other portions of the CD21
      molecule, triggered B cell homotypic aggregation. Beads coated with the same CD21
      ligands, although inactive alone, synergized with anti-IgM mAb in greatly
      increasing (20- to 180-fold) mRNA levels of the c-fos nuclear proto-oncogene.
      Signaling via CD21 was tyrosine kinase dependent. Levels of c-myc mRNA were not
      altered by CD21 ligands. Anti-CD19 and anti-CD35 mAb did not augment signaling
      via membrane IgM as assessed by changes in c-fos mRNA levels. These findings
      indicate that CD21 ligands binding to the C3dg/EBV-binding site of CD21 markedly
      augment B cell activation initiated by Ag receptor ligation via a selective, c
      fos-dependent signaling pathway.

PMID- 7525707
TI  - A predominant viral epitope recognized by T cells from the periphery and
      demyelinating lesions of SJL/J mice infected with Theiler's virus is located
      within VP1(233-244).
AB  - The intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV)
      into susceptible strains of mice results in a chronic, immune-mediated
      demyelinating disease that shares many features with human multiple sclerosis. As
      with human MS, T lymphocytes seem to be critically important for the pathogenesis
      of this virally induced, demyelinating disease. Therefore, determining the fine
      specificity of the T cell response may be essential for elucidating the
      mechanism(s) involved in demyelination. By using fusion proteins and synthetic
      peptides, we have initially identified a region within the amino acid residues
      233 to 250 of the VP1 capsid protein of Theiler's virus that is recognized by T
      cells from either TMEV-immunized or TMEV-infected, demyelination-susceptible
      SJL/J mice. A T lymphocyte precursor frequency analysis indicates that a major
      TMEV-reactive T cell population in the periphery of virus-infected mice
      recognizes this VP1 region. The fine epitope specificity has been further
      determined to be within VP1(233-244) using additional synthetic peptides. VP1(233
      244)-specific T cells seem to represent a significant population of TMEV-reactive
      T lymphocytes within the demyelinating lesions, because such T cells have been
      cloned from the spinal cords of infected mice. Interestingly, all TMEV-specific T
      cell clones derived from the demyelinating lesions, regardless of epitope
      specificity, produce IFN-gamma on stimulation and thus may play a critical role
      in the recruitment and activation of inflammatory cells leading to demyelination.
      Taken together, these data suggest that a T cell response against VP1(233-244) is
      involved in the pathogenesis of TMEV-induced demyelinating disease.

PMID- 7525708
TI  - Evidence for a specific post-transcriptional mechanism controlling the expression
      of HLA-DQ, but not -DR and -DP, molecules.
AB  - It is generally believed that the various MHC class II molecules are expressed
      coordinately in B cells. To investigate this aspect in more detail, interspecies
      somatic cell hybrids were constructed between Raji or RJ 2.2.5 (a class II
      negative derivative of Raji) human B cells and M12.4.1 mouse B cells. In both
      types of hybrids, HLA-DR and -DP, but not -DQ, molecules were expressed at the
      cell surface. The specific lack of expression of DQ Ags correlated with
      undetectability of newly synthesized DQ alpha beta heterodimers, as assessed by
      biosynthetic labeling and immunoprecipitation with a variety of DQ-specific mAbs.
      Studies at the mRNA level showed that apparently normal DQ alpha and DQ beta
      transcripts were present in the hybrids at levels comparable, if not higher, with
      the levels of DR- and DP-specific transcripts. From these results, we conclude
      that lack of appreciable amount of DQ molecules in the hybrids is caused by a
      post-transcriptional block. To date, these findings represent a rather unique
      example of noncoordinate expression of MHC class II Ags caused by distinct post
      transcriptional mechanisms. These data may be relevant to a more correct
      interpretation of the functional role of the various MHC class II molecules,
      particularly with regard to the well-known association of HLA-DQ with many
      autoimmune diseases. Possible mechanisms at the basis of the distinct control of
      expression within the MHC class II molecular pool are discussed.

PMID- 7525709
TI  - Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes.
      Comparison of their immunogenicity and capacity to induce protective immunity.
AB  - We compared the effectiveness of several recombinant influenza and vaccinia
      viruses to induce a malaria-specific immune response. The CD8+ T cell epitope of
      the circumsporozoite (CS) protein of Plasmodium yoelii, a rodent malaria
      parasite, was expressed in two distinct influenza virus proteins, the
      hemagglutinin and the neuraminidase. These recombinant viruses were found to be
      equally efficient at inducing CS-specific CD8+ T cells in mice. A third
      recombinant virus, which expresses a B cell epitope of the CS protein, induced
      neutralizing anti-sporozoite Abs. Expression in the same recombinant virus of the
      CD8+ T cell epitope and of the B cell epitope did not impair the capacity of this
      recombinant virus to induce malaria-specific CD8+ T cells and neutralizing Abs.
      The immunogenicity of a vaccinia virus, expressing the entire CS protein, was
      compared with that of a highly attenuated vaccinia strain expressing the same
      protein and with that of another vaccinia virus expressing only the CD8+ T cell
      epitope. All three vaccinia virus recombinants elicited CS-specific CD8+ cells
      and a potent inhibitory response against pre-erythrocytic stages of malaria
      parasites. Optimal levels of anti-sporozoite Abs, inhibition of liver stage
      development, and protection against malaria infection resulted from repeatedly
      immunizing the animals with recombinant influenza viruses followed by boosters
      with a recombinant vaccinia virus. These findings support the concept that live
      viral vectors expressing the appropriate proteins and/or epitopes can be used as
      promising vaccine candidates.

PMID- 7525710
TI  - Signals from platelet/endothelial cell adhesion molecule enhance the adhesive
      activity of the very late antigen-4 integrin of human CD34+ hemopoietic
      progenitor cells.
AB  - Adhesive interactions between human CD34+ hemopoietic progenitor cells and bone
      marrow stromal cells control the localization, proliferation, and differentiation
      of CD34+ cells. Changes in adhesive interactions may contribute to the
      mobilization of CD34+ cells to the blood induced by chemotherapy and cytokines.
      Thus, the identities and functional states of adhesion receptors are critical
      properties of CD34+ cells. Here, we confirm that the adhesion receptors very late
      antigen-4 (VLA-4), LFA-1, and platelet/endothelial cell adhesion molecule-1
      (PECAM-1) are expressed on the CD34+ cell line KG1a and on CD34+ normal, steady
      state bone marrow cells. Therapeutically mobilized CD34+ cells express similar
      levels of PECAM-1 but reduced levels of VLA-4 and LFA-1 in comparison with steady
      state bone marrow cells. Integrin adhesive activity was measured from the binding
      of PKH 26- or phycoerythrin-labeled CD34+ cells to FITC-labeled Chinese hamster
      ovary (CHO) cells expressing vascular CAM-1 (VCAM-1) or intercellular CAM-1,
      which are ligands for VLA-4 and LFA-1, respectively. Incubation mixtures were
      analyzed by flow cytometry for the loss of free CD34+ cells and gain of CD34(+)
      CHO cell aggregates. VLA-4 mediates the strong and specific adhesion of KG1a
      cells and bone marrow CD34+ cells to VCAM-1-transfected CHO cells. CD34+ cells
      mobilized with granulocyte colony stimulating factor (G-CSF) or cyclophosphamide
      also bind VCAM-1 via VLA-4. The VLA-4-mediated adhesion of all CD34+ cells to
      VCAM-1 is enhanced by Abs to the coexpressed adhesion receptor PECAM-1,
      implicating signals transmitted from PECAM-1 as determinants of VLA-4 integrin
      activity. VLA-4 function in CD34+ cells mobilized with G-CSF or cyclophosphamide
      is equivalent to steady state CD34+ cells. LFA-1 mediates minimal adhesion
      between CD34+ cells and intercellular CAM-1 transfected CHO cells and is
      refractory to PECAM-1 modulation. We infer that VLA-4, but not LFA-1, contributes
      to the constitutive adhesive phenotype of CD34+ cells. PECAM-1 is probably one of
      several receptors that control adhesive interactions between hemopoietic
      progenitors and target cells by regulating the activation states of specific
      integrins.

PMID- 7525711
TI  - Activation of LPS-inducible genes by the antitumor agent 5,6-dimethylxanthenone-4
      acetic acid in primary murine macrophages. Dissection of signaling pathways
      leading to gene induction and tyrosine phosphorylation.
AB  - The synthetic flavone analogue 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA)
      has shown promise as an antitumor agent and is currently a candidate for clinical
      trials. Because 5,6-MeXAA has been shown in a murine macrophage and a human
      myelomonocytic cell line to induce TNF-alpha mRNA and to activate macrophages to
      become tumoricidal, actions that are shared with bacterial LPS, we sought to
      determine the level of LPS mimetic activity exhibited by this low m.w. macrophage
      activating agent. To elucidate its mechanisms of action, the capacity to induce a
      panel of LPS-inducible genes was assessed. 5,6-MeXAA was found to induce a subset
      of LPS-inducible genes within the panel in both Lpsn and Lpsd primary murine
      macrophages. Of the six LPS-inducible genes examined, there was marked induction
      of IP-10, D8, and D3; low induction of TNF-alpha gene expression; and
      insignificant induction of TNFR-2 and IL-1 beta genes. 5,6-MeXAA was also found
      to be a potent inducer of IFNs in macrophages of both strains, and of increased
      expression of the genes that encode the IFN regulatory factors IRF-1, IRF-2, and
      ICSBP. In contrast with LPS, 5,6-MeXAA failed to induce significantly any of the
      40- to 45-kDa tyrosine phosphoproteins induced by LPS. These data suggest that
      5,6-MeXAA shares with LPS certain biochemical pathways that lead to gene
      induction and allow for the additional dissection of the relationship of tyrosine
      phosphorylation and the expression of specific genes.

PMID- 7525712
TI  - Production and function of murine macrophage inflammatory protein-1 alpha in
      bleomycin-induced lung injury.
AB  - We investigated the role of macrophage inflammatory protein-1 alpha (MIP-1 alpha)
      in bleomycin-induced lung injury, a model of interstitial lung disease. Bleomycin
      stimulates a T cell-dependent pulmonary inflammatory response characterized by an
      increase in leukocyte infiltration, fibroblast proliferation, and collagen
      synthesis. Intratracheal challenge of CBA/J mice with bleomycin resulted in a
      significant time-dependent increase in MIP-1 alpha protein levels both in whole
      lung homogenates and bronchoalveolar lavage fluid. The kinetics of MIP-1 alpha
      expression were biphasic, with the first peak occurring at 2 days
      postinstillation and the second peak at 16 days. These levels of Ag expression
      temporally correlated with the accumulation of granulocytes, lymphocytes, and
      mononuclear phagocytes in the lung. In addition, immunohistochemical staining
      identified alveolar macrophages and bronchial epithelial cells as the primary
      cellular sources of MIP-1 alpha production. Interestingly, passive immunization
      of bleomycin-challenged mice with anti-MIP-1 alpha Abs significantly reduced
      pulmonary mononuclear phagocyte accumulation and fibrosis. These experiments
      establish that MIP-1 alpha protein is expressed in the lungs of bleomycin-treated
      mice and provide evidence that MIP-1 alpha promotes leukocyte accumulation and
      activation. Furthermore, these findings support the notion that leukocyte
      accumulation and activation are linked to fibrosis.

PMID- 7525713
TI  - Regulation of monocyte integrin expression by beta-family chemokines.
AB  - In the present study we investigated the ability of three monocyte chemokines
      (MCP-1, MIP-1 alpha, and RANTES) to modulate monocyte adhesion molecules in an
      attempt to evaluate their potential to induce tissue infiltration of macrophages
      in vivo. All three chemokines tested induced increased expression of the alpha
      chains of two members of beta 2 family of integrins, CD11b and CD11c, and their
      common beta-chain (CD18). They had no effect on CD11a expression. Enhancement of
      CD11b and CD11c was dose dependent and followed a distinct time course with peak
      levels at 4 h. Levels declined to reach basal levels by 24 h. In contrast, IL-1
      induced enhancement remained high after 24 h of stimulation. However, the
      increases caused by chemokines were not mediated by IL-1 as indicated by lack of
      inhibition by the IL-1R antagonist. Studies on the mechanism of integrin up
      regulation showed that mobilization of cytosolic free calcium is an important
      signaling event in this response and that up-regulation is associated with
      mobilization from intracellular pools mediated by microtubules. Enhanced CD11b
      and CD11c expression by chemokines was also found to result in enhancement of
      monocyte binding to endothelial cells. Further studies indicated that monocyte
      binding to endothelial cells follows similar dose-response kinetics as the up
      regulation of integrins and can be partially blocked by Abs to CD11b and CD11c.
      These results suggest that modulation of the integrin expression by chemokines
      may facilitate the tissue trafficking of monocytes during inflammation.

PMID- 7525714
TI  - Lung monocyte chemoattractant protein-1 gene expression in bleomycin-induced
      pulmonary fibrosis.
AB  - Recent studies indicate that monocyte chemoattractant protein-1 (MCP-1) may play
      an important role in pulmonary inflammation. In vitro studies show that a number
      of cell types are capable of producing MCP-1. In this study, MCP-1 expression in
      lungs of rats with bleomycin (BLM)-induced pulmonary fibrosis is examined to
      evaluate its cellular origin and potential role in pathogenesis. Lung fibrosis
      was induced in male Fisher 344 rats by endotracheal injection on day 0. On
      selected days after injection, lungs were harvested for in situ and Northern
      hybridization analyses for MCP-1 mRNA expression, immunochemical and
      histochemical analyses for MCP-1 protein expression, and identification of cell
      type. Northern analysis revealed significant elevation in lung MCP-1 mRNA
      expression beginning on day 3 post-BLM treatment, increasing to a peak on day 7,
      and then decreasing toward control levels after day 21. In situ hybridization
      combined with histochemical staining with chromotrope 2R indicate that most of
      the cells expressing MCP-1 mRNA at these time points are primarily eosinophils. A
      few scattered reactive fibroblasts, some mononuclear cells, epithelial cells, and
      cells of certain blood vessel walls also express this mRNA. Increased MCP-1
      protein expression also was found to be predominantly within and adjacent to
      eosinophils. The eosinophils expressing this mRNA were found predominantly within
      areas of active fibrosis. The kinetics of increase in the number of cells
      expressing significant MCP-1 mRNA in lung sections paralleled that for MCP-1 mRNA
      expression, as assessed by Northern analysis. These results, for the first time,
      demonstrate that MCP-1 is up-regulated significantly in this rat animal model,
      and that infiltrating eosinophils represent the major cellular source for this
      increased MCP-1 expression.

PMID- 7525716
TI  - HLA restriction and TCR usage of T lymphocytes specific for a novel candidate
      autoantigen, X2 MBP, in multiple sclerosis.
AB  - Previous investigations of the major 18.5-kDa isoform of myelin basic protein
      (MBP) as a target autoantigen in multiple sclerosis (MS) have failed to identify
      an epitope uniformly recognized with higher frequency in MS patients compared
      with controls. Because remyelination has been observed in MS plaques, we were
      prompted to investigate T cells specific for myelin protein isoforms with up
      regulated expression during remyelination. We have recently described such T
      cells that recognize the exon 2-encoded region of MBP (X2 MBP), a sequence
      included in the 21.5- and 20.2-kDa isoforms of MBP. These cells were shown to be
      CD4+, HLA class II restricted, and cytolytic. In members of one multiplex MS
      family, X2 MBP-specific T lymphocytes were as prevalent as T cells specific for
      immunodominant regions within the major 18.5-kDa isoform of MBP. The present
      study characterizes X2 MBP-specific T cell responses in additional multiplex MS
      family members as well as in heterogeneous (non-familial) MS patients and in
      healthy controls. The frequencies of X2 MBP-specific T cells in each of the
      affected family members from two of three MS families were significantly
      increased as compared with both the heterogeneous MS group and the healthy
      control group. Also, X2 MBP-specific T cell lines from affected family members
      were primarily restricted to molecules encoded by the DR2/DQw1 allele. Although
      TCR usage was generally heterogeneous, there was evidence of intraindividual
      sequence identity. These data suggest that: 1) Myelin proteins with up-regulated
      expression during the course of disease should be considered as candidate
      autoantigens in MS. 2) The functional basis for the association of DR2/DQw1
      inheritance with MS susceptibility may be related to presentation of autoantigens
      by this allele. 3) TCR therapy will need to be individually tailored to target
      the most prevalent autoantigen-specific response.

PMID- 7525717
TI  - Polyclonal B cell activation induced by herpesvirus saimiri-transformed human
      CD4+ T cell clones. Role for membrane TNF-alpha/TNF-alpha receptors and CD2/CD58
      interactions.
AB  - We have shown that in vitro infection herpesvirus saimiri (HVS) can transform
      human CD4+ T cell clones with defined Th1 or Th2 cytokine profiles to continuous
      growth. We report here that transformation with HVS enabled both Th1 and Th2
      clones to stimulate proliferation and Ig production by autologous or allogeneic B
      cells in the absence of stimulants. The polyclonal B cell-activating property of
      HVS-transformed clones was not related to free virus or soluble cytokines, but
      rather was dependent on an Ag-nonspecific, MHC-unrestricted, contact-dependent
      mechanism. T blasts from unstimulated HVS-transformed clones did not express CD40
      ligand (CD40L) mRNA or CD40L protein, whereas a proportion of them constitutively
      expressed membrane TNF (mTNF)-alpha. Both CD40L and mTNF-alpha were detectable on
      either uninfected or HVS-transformed clones upon mitogen stimulation. The
      activation of high-density B cells by unstimulated HVS-transformed clones was not
      inhibited by soluble CD40-Ig fusion protein, but was strongly reduced by either
      anti-TNF-alpha or anti-TNF-alpha receptor (TNF-alpha R) mAbs. Addition of anti
      CD2 and/or anti-CD58 mAbs was also inhibitory, but no additive effect with anti
      TNF-alpha and/or anti-TNF-alpha R mAbs was observed. Neither anti-IL-2 nor CD40
      Ig inhibited the proliferation of naive IgD+ B cells cocultured with fixed
      unstimulated HVS-transformed clones, whereas a combination of anti-TNF-alpha and
      anti-TNF-alpha R mAbs was inhibitory. In addition, fixed unstimulated HVS
      transformed clones induced Ig synthesis in IgD+ naive B cells even in the absence
      of exogenous IL-2. Data suggest that both the mTNF-alpha/TNF-alpha R and the
      CD2/CD58 pathways, but not the CD40L-CD40 interaction plus secreted cytokines,
      are involved in the unusual mode of B cell activation exerted by CD4+ HVS
      transformed clones.

PMID- 7525715
TI  - Idiotype-cytokine fusion proteins as cancer vaccines. Relative efficacy of IL-2,
      IL-4, and granulocyte-macrophage colony-stimulating factor.
AB  - Idiotypic determinants, antigenic sites expressed on the variable region of Ig
      molecules of malignant B cells, represent tumor-specific Ags but are weak
      immunogens. We have previously shown that the immunogenicity can be dramatically
      increased by fusing tumor Id to granulocyte macrophage (GM)-CSF. Here, we
      demonstrate that fusion proteins with IL-2 or IL-4 can also be highly
      immunogenic. Co-immunization of these fusion proteins with another Id
      demonstrated the importance of physical linkage between the cytokine and relevant
      Ag for this enhancement. All three fusion proteins are capable of eliciting
      significant levels of specific Abs against the Id without the use of carrier
      proteins or adjuvants, although the GM-CSF fusion protein appeared to be unique
      in its ability to induce higher titers of anti-Id Abs in the primary response.
      Furthermore, the Id-IL-2 fusion protein induced high titers of IgG2a and IgG3
      anti-Id Abs, whereas the Id-IL-4 and Id-GM-CSF fusion proteins did not. Despite
      the differences, tumor protection was comparable in all mice having significant
      titers of anti-Id Abs, regardless of the fusion protein used. We concluded that
      Id-cytokine fusion proteins are potent immunogens that can elicit significant
      antitumor immunity. The general approach of fusing a cytokine to a potential Ag
      may be applicable to the design of vaccines for immunotherapy of other types of
      tumors as well as for other pathogens and disease states.

PMID- 7525718
TI  - Regulation of adhesion of CD4+ T lymphocytes to intact or heparinase-treated
      subendothelial extracellular matrix by diffusible or anchored RANTES and MIP-1
      beta.
AB  - Chemokines, a superfamily of 8- to 11-kDa mediators of inflammation, affect the
      attachment of immune cells to vascular endothelia by binding to cell surface
      glycosaminoglycans. We analyzed whether chemokines are also involved in
      interactions between CD4+ T lymphocytes and the subendothelial extracellular
      matrix (ECM). Soluble mediators, such as MIP-1 beta and RANTES, induced the
      binding of resting human CD4+ T cells to ECM in an integrin-dependent manner.
      Both MIP-1 beta and RANTES bound to intact ECM and retained their adhesive
      properties, and moreover, ECM-bound RANTES and MIP-1 beta prolonged the time
      course of interactions between the CD4+ T cells and the ECM. Because the adhesive
      effect of these chemokines was restricted by an inhibitor of GTP-binding
      proteins, the adhesive effect of ECM-bound RANTES and MIP-1 beta, which requires
      an intact cytoskeleton, seems to involve activation of a G protein-linked
      receptor. MIP-1 beta and RANTES exert their pro-adhesive effects through
      interactions with glycosaminoglycans, because heparinase-treated ECM did not
      bound chemokines and because the chemokines ability to induce T cell adhesion was
      abrogated if: 1) either of the chemokines is pretreaed with heparin or heparan
      sulfate (HS), 2) HS is removed from intact ECM by heparinase, an HS-specific
      endoglycosidase, or 3) the ECM-bound chemokines are released by pretreatment with
      heparinase. Hence, the adhesive effects of immobilized chemokines is not
      restricted to T cells interacting with endothelial cells, but also affects the
      migration of immune cells which reside and function in the context of ECM.

PMID- 7525719
TI  - C-C chemokines induce the chemotaxis of NK and IL-2-activated NK cells. Role for
      G proteins.
AB  - The C-C chemokines MIP-1 alpha, MCP-1, and RANTES, but not MIP-1 beta, induce the
      chemotaxis of NK and IL-2-activated NK (IANK) cells, as determined in
      microchemotaxis assay. Only RANTES and MCP-1, but not MIP-1 alpha were able to
      induce the chemokinesis of NK cells. In contrast, none of the C-C chemokines
      tested was able to induce the chemokinesis of IANK cells. IANK cell chemotaxis in
      response to MCP-1 or RANTES but not MIP-1 alpha, was inhibited by pertussis toxin
      (PT). In contrast, cholera toxin (CT) inhibited the ability of all three
      chemokines to induce the chemotaxis of IANK cells. IANK cells intoxicated with PT
      lost their ability to migrate in response to RANTES and MCP-1 but not MIP-1
      alpha, whereas those intoxicated with CT lost their ability to migrate in
      response to the three C-C chemokines tested. These results suggest that guanine
      nucleotide binding (G) proteins are coupled to C-C chemokine receptors in IANK
      cells. Subsequently, we observed that MIP-1 alpha, MCP-1, and RANTES, but not MIP
      1 beta, enhance the binding of guanosine 5'-O-(thiotriphosphate), and increase
      the hydrolysis of [32P]GTP in IANK cell membranes. Further analysis showed that
      MIP-1 alpha, RANTES, or MCP-1 did not enhance GTP binding in membranes prepared
      from IANK cells intoxicated with CT, whereas only RANTES and MCP-1 but not MIP-1
      alpha lost their ability to enhance GTP binding to IANK cell membranes prepared
      from PT-intoxicated cells. The differential inhibitory activity of CT and PT
      suggests that C-C chemokine receptors are coupled to different G proteins in IANK
      cells.

PMID- 7525720
TI  - Expression of CD43 on murine and human pluripotent hematopoietic stem cells.
AB  - To understand regulation of hemopoiesis, it would be helpful to identify
      physiologically relevant function-associated molecules on stem cells. Here, we
      report the detailed examination of CD43 expression on murine and human
      pluripotent hemopoietic stem cells. Mouse stem cells were found within the
      Ly6+Lin-CD43high subpopulation of bone marrow. These cells, upon transfer into
      SCID mice, caused rapid repopulation of thymus, spleen, and bone marrow.
      Retransfer of bone marrow cells from primary SCID recipients of Ly6+Lin-CD43high
      cells into secondary recipients resulted in repopulation of lymphohemopoietic
      cells. All Ly6+Lin-CD43high cells were found to express high levels of c-kit. In
      contrast, Ly6+Lin-CD43-/low cells caused limited and variable thymic and splenic
      repopulation. These cells failed to repopulate the marrow cavity and did not
      contain retransplantable stem cells. These data indicate that murine pluripotent
      stem cells express high levels of CD43. Examination of human fetal bone marrow
      cells revealed a population of CD34+CD38-CD43+ cells. When single sorted cells
      with this phenotype were cultured in vitro, they were able to produce colonies
      with a dispersed growth pattern. Cells with this growth pattern have previously
      been shown to have myeloid and lymphoid growth potentials and extensive self
      renewal capacity. Furthermore, CD34+CD38-HLA-DR+ cells, recently shown to be
      highly enriched in stem cell activity, expressed relatively high levels of CD43.
      Because CD43 has recently been shown to bind to intercellular adhesion molecule
      1, these data suggest a possible role for CD43 in the regulation of hemopoiesis.

PMID- 7525721
TI  - Coculture of TCR peptide-specific T cells with basic protein-specific T cells
      inhibits proliferation, IL-3 mRNA, and transfer of experimental autoimmune
      encephalomyelitis.
AB  - TCR peptides, namely V beta 8.2-39-59 or the minimal idiotope, V beta 8-44-54,
      can treat experimental autoimmune encephalomyelitis (EAE) in Lewis rats,
      presumably by activating naturally induced TCR peptide-specific T cells that
      arise in response to the focused appearance of V beta 8.2+ encephalitogenic T
      cells. The purpose of the present study was to evaluate the mechanisms by which
      TCR peptides inhibit EAE. We found that treatment of EAE with the V beta 8.2-39
      59 peptide did not induce any evidence of DNA fragmentation (apoptosis) in spinal
      cord cells isolated from clinically well rats, implicating a regulatory rather
      than a deletional mechanism. TCR peptide-specific T cell lines failed to inhibit
      EAE induced by already activated BP-specific T cells when the two T cell
      specificities were co-injected. However, coculturing the encephalitogenic T cells
      in the presence of the regulatory T cells during the activation step before
      transfer almost completely inhibited the induction of EAE. Inhibition could be
      induced by direct contact between the two cell types or by soluble factors
      produced in a transwell system, but was greatly enhanced when soluble V beta 8.2
      39-59 peptide was used to optimally activate the regulatory T cells. The
      inhibition was regulatory cell dose dependent, and was reflected in vitro by
      reduced proliferation response and mRNA production for IL-3, and to a lesser
      extent, IFN-gamma and IL-2. These results indicate that regulation induced by TCR
      peptides involves cell-cell interactions that lead to the production and release
      of soluble factors that locally inhibit the activation of encephalitogenic T
      cells expressing MHC-bound idiotopes of the target V beta-chain, and possibly
      "bystander" specificities expressing different V beta-chains.

PMID- 7525723
TI  - The mechanism of autoantibody production in an autoimmune MRL/lpr mouse.
AB  - Rheumatoid factors (RF) and anti-DNA Abs from MRL/lpr mice have features similar
      to Abs directed toward foreign Ags, indicating a role of specific activation by
      Ags during disease. But our previous studies and analogous studies from others
      concentrated on a limited subset of hybridomas selected on the basis of Ag
      binding to well characterized target autoantigens. Thus, it has been unclear to
      what extent clonal expansion is restricted to identifiable autospecificities. To
      obtain a more complete picture of disease-associated autoantibody production, we
      designed the following experiment. A large number of B cell hybridomas were
      generated from the spleen of an MRL/lpr mouse and then analyzed for self
      specificity, sequence, and clonal relationship. Surprisingly, we found that
      clonal expansion was limited to only a few autospecificities, implying a unique
      property of this response. In addition, we used Southern blotting with heavy and
      L chain constant region probes to screen both RF and non-RF hybridomas for
      membership in clones, one of which was first identified among RF hybridomas. We
      found no non-RF members of this clone. The size and number of mutations of this
      clone were sufficient for us to conclude that nonspecific (i.e., non-RF) mutant
      members are rapidly lost. Had an Ag other than IgG2a been driving clonal
      expansion, we should have seen mutants that retained spectificity for that Ag but
      that lost specificity for IgG2a. This observation, along with the restriction of
      clonal expansion to a few autospecificities, provides strong evidence that normal
      autoantigens themselves drive autoantibody clonal expansion.

PMID- 7525722
TI  - Characterization of the murine B7-1 genomic locus reveals an additional exon
      encoding an alternative cytoplasmic domain and a chromosomal location of
      chromosome 16, band B5.
AB  - The murine B7-1 (mB7-1) molecule expressed on APCs delivers a costimulatory
      signal for T cell activation through its T cell counter-receptor CD28, resulting
      in T cell proliferation and IL-2 production. Signaling through the TCR in the
      absence of CD28 signaling results in T cell anergy. We have analyzed the genomic
      structure of mB7-1 and here describe the identification of a previously
      unrecognized sixth exon at the far 3' end of the locus, which encodes an
      alternative cytoplasmic domain. Reverse transcriptase-PCR amplification of mB7-1
      transcripts demonstrates that exon 6 is functionally spliced to the transmembrane
      encoding exon 4. Furthermore, using 5' rapid amplification of cDNA ends, we
      determined that the 5'-untranslated region extends over 1505 bp beyond the
      previously reported transcriptional start site. In addition, we report the
      chromosomal location of mB7-1 to chromosome 16, band B5.

PMID- 7525724
TI  - TNF-alpha and IFN-gamma stimulate a macrophage precursor cell line to kill
      Listeria monocytogenes in a nitric oxide-independent manner.
AB  - Macrophages are important effector cells for resolving infection with the
      facultative intracellular bacterium Listeria monocytogenes. However, not all
      macrophages have the ability to kill this organism. Certain factors, such as
      cytokines, are apparently required for induction of macrophage bactericidal
      activity. In vivo studies have shown that both TNF-alpha and IFN-gamma play
      important roles in resistance against Listeria. Yet whether they act directly on
      macrophages has been difficult to determine, because homogeneous populations of
      cells that can be induced to express microbicidal activity have not been
      available. Instead, bactericidal macrophages are typically found in heterogeneous
      exudates, such as those elicited by inflammatory agents. In this study we show
      that sequential stimulation with TNF-alpha and IFN-gamma induces the
      nonphagocytic, nonbactericidal mouse macrophage precursor hybrid cell line W1C3
      to phagocytose and kill Listeria efficiently. This provides the first direct
      evidence that TNF-alpha and IFN-gamma are both necessary and sufficient to induce
      macrophages to kill Listeria, and that they act directly on macrophages. Data
      presented here also show that TNF-alpha and IFN-gamma induced the macrophages to
      produce large amounts of reactive nitrogen intermediates (RNI), but complete
      inhibition of RNI generation did not decrease bactericidal activity. This
      indicates that induction of listericidal activity in these cells does not require
      generation of RNI. Taken together, these findings suggest that TNF-alpha and IFN
      gamma act in synergy directly on at least some macrophages to induce them to
      express listericidal activity in a RNI-independent manner.

PMID- 7525725
TI  - Protective cytotoxic T lymphocytes are induced during murine infection with
      Chlamydia trachomatis.
AB  - T cell responses are often an important component in immunity to organisms that
      replicate intracellularly. Cytotoxic T lymphocyte (CTL) recognition of peptide Ag
      in the context of MHC class I molecules results in lysis of infected cells and
      the release of cytokines including IFN-gamma. Members of the genus Chlamydia are
      obligate intracellular pathogens that cause blindness and sexually transmitted
      disease worldwide. Even though it replicates within a membrane-bound vacuole,
      Chlamydia trachomatis may elicit a CTL response if Chlamydia Ags are present in
      the cytoplasmic compartment where they can be processed for presentation and
      bound by MHC class I. In this study, we characterized a CTL line derived from
      mice infected with C. trachomatis. This CTL line is specific for, and able to
      lyse, Chlamydia-infected cells. The peptide epitope recognized by this CTL line
      is present on infected cells, and is presented to the CTL by the classical MHC
      class I molecule H-2 Ld. Adoptive transfer of this CTL line into an infected
      mouse affords protection, and this protection requires the activity of IFN-gamma.

PMID- 7525727
TI  - Elevated expression of Th1 cytokines and nitric oxide synthase in the lungs of
      vaccinated mice after challenge infection with Schistosoma mansoni.
AB  - C57BL/6 mice were vaccinated with irradiated cercariae of Schistosoma mansoni,
      and, at various times after challenge infection, total lung mRNA was isolated to
      assess the induction of several cytokines that previously had been shown in in
      vitro studies to be involved in the activation of macrophages and/or endothelial
      cells for nitric oxide (NO) production and killing of schistosomula. Vaccinated
      mice demonstrated a highly significant increase in IFN-gamma mRNA upon subsequent
      infection when compared with infected nonvaccinated controls. A similar, although
      less dramatic, increase in two other macrophage-activating cytokines, TNF-alpha
      and IL-2, also was observed. In contrast, although the Th2 cytokines IL-4, IL-5,
      IL-10, and IL-13 were elevated in challenged vaccinated animals, only IL-10 and
      IL-13 showed increases that were significant with respect to the mRNA levels
      observed in challenged controls. Neutralization of IFN-gamma reduced immunity in
      vaccinated animals and resulted in decreased IFN-gamma, IL-2, IL-10, TNF-alpha,
      and IL-12 p40 but markedly increased IL-4, IL-5, and IL-13 mRNA expression and
      serum IgE levels. Pulmonary NO synthase expression was elevated in immunized mice
      at a time at which immune elimination of schistosomula is believed to occur.
      Moreover, suppression of NO synthase activity with the inhibitor aminoguanidine
      reduced immunity, as measured by a 32 to 33% increase in worm burden. Together,
      these data support previous in vitro studies that suggest a role for NO in
      schistosomulum killing. Furthermore, the observation that the down-regulatory
      cytokines IL-4, IL-10, and IL-13 are induced together with IFN-gamma may provide
      an explanation for the failure of this vaccine to provide complete protection.

PMID- 7525728
TI  - Acyclic analogue of lipid A stimulates TNF-alpha and arachidonate release via a
      unique LPS-signaling pathway.
AB  - LPS has been implicated in the pathogenesis of Gram-negative bacterial sepsis.
      Despite intensive efforts to define the LPS-signal transduction pathway, CD14 is
      the sole molecule clearly demonstrated to possess signaling capabilities.
      However, it remains unclear whether CD14 is the only LPS-signaling molecule
      expressed in phagocytes and how CD14-mediated signaling occurs. Compound SDZ
      280.961 is a synthetic triacylated amino acid that structurally resembles the
      reducing sugar moiety of lipid A. SDZ 280.961 effectively stimulated TNF-alpha
      release from human PBMC. Co-incubation of PBMC with the specific LPS inhibitor
      Rhodobacter sphaeroides lipid A inhibited SDZ 280.961-mediated stimulation of TNF
      alpha release, indicating that this analogue signals mononuclear cells via a LPS
      activated signaling pathway. Induction of TNF-alpha release from mononuclear
      cells by SDZ 280.961 was strongly dependent on the presence of serum and was
      enabled by the presence of purified LPS-binding protein, characteristics of CD14
      mediated signaling. In contrast, SDZ 280.961-mediated signaling was not inhibited
      by blocking anti-CD14 mAbs. A Chinese hamster ovary fibroblast line transfected
      with human CD14, which responds to LPS in a manner qualitatively similar to that
      of macrophage cell lines, failed to respond to SDZ 280.961. Taken together, these
      data suggest that the lipid A analogue SDZ 280.961 activates monocytes via a
      unique LPS-signal transduction pathway that appears to be independent of CD14.

PMID- 7525729
TI  - Local production of IFN-gamma abrogates the intraocular immune privilege in
      transgenic mice and prevents the induction of ACAID.
AB  - The eye represents an immunologically privileged site with specific properties
      mediated by immunosuppressive constituents of the intraocular fluids. This
      system, termed ACAID (anterior chamber-associated immune deviation), was
      originally attributed to the anterior chamber of the eye, and is characterized by
      impairment of the cellular immune response, including a lack of delayed type
      hypersensitivity (DTH) reaction in response to intraocularly presented Ag and
      decreased cytotoxicity of T cells. We created a transgenic mouse with ectopic
      expression of IFN-gamma in the photoreceptors of the retina to study the effects
      of this cytokine on the immunosuppressive properties of the eye with special
      regard to the posterior chamber. BALB/c-derived transgenic and nontransgenic mice
      were challenged intravitreally either with allogeneic splenocytes from C57Bl/6
      mice or with BSA, in IFA, and tested for the delayed type hypersensitivity
      reaction to BSA by intrapinnal injection of the same Ag in the ear 7 days later.
      Pathologic changes of the eyes were evaluated by histology and
      immunohistochemistry. We found that transgenic mice developed an increased amount
      of ocular inflammation in response to both Ags compared with the nontransgenic
      controls. Furthermore, transgenic mice showed a marked DTH reaction to BSA,
      whereas nontransgenic mice did not. Our results indicate that local IFN-gamma
      production disturbs the immunosuppressive properties of the eye and prevents the
      induction of ACAID in response to intraocularly presented Ag. The data confirm
      the extension of the intraocular immune privilege to the posterior chamber of the
      eye.

PMID- 7525726
TI  - Regulation of T helper cell responses in experimental murine schistosomiasis by
      IL-10. Effect on expression of B7 and B7-2 costimulatory molecules by
      macrophages.
AB  - Granulomatous inflammation in schistosomiasis is a manifestation of cell-mediated
      hypersensitivity to parasite egg Ags that is predictably reduced in size over the
      course of the disease. This down-regulation may reflect a state of anergy in the
      T cells mediating granuloma formation after interaction with accessory cells
      incapable of providing full stimulation. The present studies were conducted to
      investigate this mechanism at the molecular level. We found that granuloma
      macrophages (GM) strongly inhibit the ability of splenic APC to stimulate egg Ag
      specific Th1 responses. This property was shown to be dependent on their
      secretion of IL-10. Moreover, activated GM in culture were found to express
      little or no costimulatory Ags B7 or B7-2. However, when their autocrine
      secretion of IL-10 was neutralized with specific mAb, GM displayed an up
      regulation of costimulatory molecules as well as of MHC class II Ags. Most
      importantly, GM cultured in the presence of anti-IL-10 mAb, acquired the ability
      to stimulate egg Ag-specific T cells. By independently blocking each of the
      induced costimulatory Ags, it appeared that B7-2 molecules provided stronger
      costimulation than B7. In separate experiments, culture supernatants from GM
      exerted a powerful inhibition of costimulatory Ag expression on Con-A-stimulated
      peritoneal exudate cells in vivo, which could similarly be attributed to IL-10.
      Our results demonstrate that IL-10 can play a critical role in the generation of
      accessory cells that, by virtue of down-regulation of costimulatory molecules,
      may be capable of inducing anergy in T cells mediating the vigorous granulomatous
      response of acute stage schistosomiasis. Our studies lend support to the
      contention that a state of unresponsiveness in pathogenic T cells may precipitate
      the down-regulation of granuloma formation and provide a molecular basis for the
      underlying mechanisms.

PMID- 7525731
TI  - Measurement of neutrophil and eosinophil adhesion to E-selectin, VCAM-1, and ICAM
      1 by the use of transfected fibroblast cell lines.
AB  - A method which enables the specific measurement of neutrophil and eosinophil
      adhesion to the endothelial cell adherence receptors E-selectin, VCAM-1 and ICAM
      1 has been developed. The method is based on continuous cultures of cell lines of
      transfected hamster kidney fibroblasts (BHK-21), that selectively express each of
      the endothelial cell adhesions molecules. Isolated granulocytes are added to the
      cultured adherent fibroblasts at a ratio of 20:1 and the cells are coincubated
      for 60 min at 37 degrees C. After removal of the nonadherent granulocytes the
      amount of adherent granulocytes could be measured by addition of detergent and a
      peroxidase substrate. Selective measurement of neutrophil and eosinophil adhesion
      was accomplished by addition of detergent to the adherent cells, collection of
      extracts followed by measurement of the concentration of an eosinophil
      (eosinophil cationic protein) and a neutrophil (myeloperoxidase) granule protein,
      respectively, in the extracts. At basal conditions neutrophils and eosinophils
      showed significant adhesion to E-selectin and eosinophils a low degree of
      adhesion to VCAM-1. Significant adhesion of neutrophils and eosinophils to ICAM-1
      and of eosinophils to VCAM-1 was selectively induced by addition of manganese
      ions (Mn2+) at a concentration of 0.5 mmol/l. Neutrophils demonstrated a
      significantly higher adhesion to E-selectin than eosinophils, while eosinophil
      adhesion to ICAM-I was significantly higher than that of neutrophils. In
      conclusion, a method to compare the adhesive capacity of neutrophil and
      eosinophil granulocytes towards specific endothelial cell adhesion molecules has
      been developed.

PMID- 7525730
TI  - Differential responses of fibroblasts from wild-type and TNF-R55-deficient mice
      to mouse and human TNF-alpha activation.
AB  - The role of the two TNF receptor types, TNF-R55 and TNF-R75, was studied on mouse
      fibroblasts, taking advantage of TNF-R55-deficient mice generated by gene
      targeting (Tnfr1 degree-mice), and selectivity of human TNF-alpha for mouse TNF
      R55. Radioligand binding assays showed that both TNF receptors were expressed on
      wild-type mouse fibroblasts, whereas normal levels of TNF-R75 were expressed on
      mouse fibroblasts isolated from Tnfr1 degree-mice. It was found that TNF-R55
      controlled four major TNF-induced fibroblast functions: (1) adhesion to leukocyte
      cell lines as well as ICAM-1, VCAM-1, CD44, and MHC class I up-regulation; (2)
      secretion of other cytokines as demonstrated by stimulated IL-6 and granulocyte
      macrophage-CSF releases; (3) cell proliferation; and (4) NF-kappa B activation.
      Stimulation through TNF-R75, in TNF-R55-deficient fibroblasts, did not have any
      effect in these functions. In general, mouse TNF-alpha (recognizing both mouse
      TNF receptors) had a higher sp. act. than human TNF-alpha (recognizing only mouse
      TNF-R55) in wild-type fibroblasts, whereas both mouse and human TNF-alpha had
      similar cytotoxic activities in WEHI 164 cells.

PMID- 7525732
TI  - Spread of hepatitis C virus among sexual partners of HCVAb positive intravenous
      drug users.
AB  - Recent studies suggest that the seroprevalence of hepatitis C virus antibodies
      (HCVAb) among sexual partners of those who are HCVAb positive is higher than in
      the general population. Moreover some studies seem to indicate that transmission
      of hepatitis C virus (HCV) occurs more readily when there is HIV infection in the
      couple. We studied the prevalence of HCVAb seropositivity among the regular
      sexual partners of 84 HCVAb positive intravenous drug users (IVDUs), by means of
      ELISA confirmed by radio immuno-adsorbent assay, 11 generation (RIBA II). The
      couples were subdivided into three groups: group 1: 30 HIV negative IVDUs and
      their HIV negative partners (HIV-/HIV-); group 2: 47 HIV positive IVDUs and their
      HIV negative partners (HIV+/HIV-); group 3: seven HIV positive IVDUs and their
      HIV positive partners (HIV+/HIV+). The seroprevalence of HCVAb among the partners
      of IVDUs was 28.6% in the couples of group 3, 12.8% in the couples of group 2 and
      no partner was positive among the couples of group 1. There was no statistically
      significant difference in HCV transmission between the couples who never used a
      condom and those who always used one. The couples of group 1 never used a condom.
      We found HCVAb seropositivity only in the partners who were in couples in whom
      HIV was present. We did not demonstrate that sexual intercourse is a means of HCV
      transmission because none of the HIV-/HIV- couples of group 1 used a condom and
      no partner was HCVAb positive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525733
TI  - Fatal melioidosis in a tourist returning from Thailand.
AB  - Severe infections with Pseudomonas pseudomallei, the causative agent of
      melioidosis, is a common cause of community acquired septicaemia in South East
      Asia and parts of Northern Australia, but infection in travellers returning to
      the United Kingdom is extremely rare. We describe the case of a tourist who
      acquired melioidosis in Thailand. Despite intensive intravenous therapy with
      antibiotics to which the organism was sensitive, the patient's infection proved
      fatal. Ps. pseudomallei was isolated from blood cultures at a late stage in his
      illness by use of a commercial blood culture system that included an antibiotic
      removal device (Bac/TAlert, Organon-Technica).

PMID- 7525734
TI  - A keratinocyte cell line synthesizes a predominant insulin-like growth factor
      binding protein (IGFBP-3) that modulates insulin-like growth factor-I action.
AB  - Insulin-like growth factor-I (IGF-I) is an important regulator of epidermal
      proliferation and has been shown in vitro to be a powerful stimulator of
      keratinocyte growth. It is synthesized by fibroblasts in the dermis, along with
      several IGF-binding proteins (IGFBPs), which are known to modulate IGF-I
      responsiveness of virtually all tissues studied. Because it was not known how or
      in what form IGF-I produced in the dermis acts on epidermal keratinocytes in
      vivo, we investigated the possible role of IGFBPs in modulating the response of
      epidermal keratinocytes to IGF-1. We show here that tIGF-I, a non-IGFBP-binding
      analogue of IGF-1, is a more potent mitogenic stimulator of the keratinocyte cell
      line HaCaT than IGF-I, suggesting that keratinocytes produce IGFBPs that modulate
      their response to IGF-I. To confirm this and to identify which IGFBPs were
      produced, we analyzed HaCaT cell-conditioned medium and mRNA, with the following
      findings: HaCaT cells produce a major IGFBP, identified as IGFBP-3, and a minor
      24-kD IGFBP, likely to be IGFBP-4. Northern analysis revealed a 2.6-kb IGFBP-3
      mRNA; however, IGFBP-4 mRNA was not detectable. We conclude that production of
      predominantly IGFBP-3 by the HaCaT cell line modulates its sensitivity to IGF-I
      stimulation. Epidermal IGFBPs thus have a potential role in vivo in the
      interaction of dermis derived IGF-I with epidermal keratinocytes.

PMID- 7525735
TI  - Cytokine gene expression in intact anagen rat hair follicles.
AB  - Substantial cellular proliferative activity is necessary to produce a mature hair
      follicle. Therefore, it is likely that cytokines and their receptors play an
      important controlling role. To provide an understanding of the mechanisms
      involved during hair growth, we investigated the expression of cytokines in rat
      anagen hair follicles. A new technique was developed that allowed the rapid
      isolation of large numbers of intact, viable, anagen, rat pelage hair follicles.
      Total RNA was isolated from these follicles using an acid-phenol-chloroform
      extraction and analyzed for cytokine expression. Using the conventional technique
      of Northern blotting, it was only possible to detect transcripts for transforming
      growth factor beta (TGF beta) and insulin-like growth factor I (IGFI). Polymerase
      chain reaction amplification of reverse-transcribed mRNA detected cDNA fragments
      for TGF beta, IGF I, IGF II, nerve growth factor beta (NGF beta), and interleukin
      1 alpha (IL-1 alpha). The amplified products were confirmed by digestion with
      restriction endonucleases. The proteins themselves for TGF beta and IGF I have
      been shown to be present within the anagen hair follicle using immunogold
      antibody labeling. This study has provided the first reported cytokine expression
      profile of rat anagen hair follicles. It is likely that the analysis of the
      pattern and timing of expression of these cytokines in the follicle will provide
      valuable insights into hair growth regulation.

PMID- 7525737
TI  - Structural features of keratin intermediate filaments.
AB  - The first step in the assembly of a keratin intermediate filament (KIF) is the
      formation of a type I/type II heterodimer molecule in which two chains become
      aligned in parallel and close axial registration to form a flexible segmented
      alpha-helical coiled-coil rope 46 nm long. The segments of coiled-coil are
      interspersed by sequences that introduce irregularities of unknown structure.
      Here we have modeled two of these, the link L2 and the heptad discontinuity
      located near the middle of segment 2B. In a model for L2, the orientation of the
      coiled-coil structure is turned through about 180 degrees over the eight residue
      stretch constituting this link segment. In contrast, the heptad discontinuity in
      segment 2B would seem to result in only minimal distortion of the coiled-coil
      rope, contrary to previous expectations. Little is known about how the
      neighboring molecules are aligned and packed within the assembled KIF.
      Crosslinking experiments with KIF have determined that two neighboring molecules
      are aligned anti-parallel and axially in three ways, and predict that similarly
      directed molecules could be overlapped by about 1 nm. The two-dimensional surface
      lattice resulting from these data predicts an axial periodicity of 22.6 nm, which
      in fact is visible by electron microscopy of shadowed KIF. Interestingly, most of
      the amino acid substitutions resulting from mutations in the keratin genes found
      in genodermatoses are clustered in this molecular overlap region. Although we do
      not yet know how the rows of antiparallel molecules fold in three dimensions to
      form an intact KIF, certain of the observed crosslinks could also occur between
      nearest neighbor parallel molecules across a four-molecule strand; that is, KIF
      may be built from bundles or protofibrils. These insights on molecular structure
      and molecular packing provide new constraints on models for KIF structure.

PMID- 7525736
TI  - Molecular basis of human piebaldism.
AB  - Piebaldism is an autosomal dominant genetic disorder of pigmentation
      characterized by congenital patches of white skin and hair that lack melanocytes.
      Piebaldism results from mutations of the KIT proto-oncogene, which encodes the
      cell-surface receptor transmembrane tyrosine kinase for an embryonic growth
      factor, Steel factor. Several pathologic mutations of the KIT gene have now been
      identified in different patients with piebaldism. Correlation of these mutations
      with the associated piebald phenotypes has led to the recognition of a hierarchy
      of three classes of mutations that result in a graded series of piebald
      phenotypes, and to improved understanding of the mechanisms that underlie
      dominant genetic disorders.

PMID- 7525738
TI  - Genetic bases of epidermolysis bullosa simplex and epidermolytic hyperkeratosis.
AB  - Keratins are the major structural proteins of the epidermis. Analyzing keratin
      gene sequences, appreciating the switch in keratin gene expression that takes
      place as epidermal cells commit to terminally differentiate, and elucidating how
      keratins assemble into 10-nm filaments have provided the foundation that has led
      to the discoveries of the genetic bases of two major classes of human skin
      diseases. In this report, we review the cell biology and human genetics of these
      diseases, epidermolysis bullosa simplex and epidermolytic hyperkeratosis. Both of
      these diseases are epidermal disorders of keratin, typified by cell fragility as
      a consequence of defects in the mechanical strength of basal epidermolysis
      bullosa simplex or suprabasal epidermolytic hyperkeratosis cells.

PMID- 7525739
TI  - Ultrastructural identification of basic abnormalities as clues to genetic
      disorders of the epidermis.
AB  - The present article discusses specific, directly gene-dependent ultrastructural
      markers of dominantly inherited epidermal disorders that serve as clues to their
      underlying molecular genetic abnormalities. These are epidermolysis bullosa
      simplex Koebner and Weber-Cockayne with rupture or non-assembly of basal cell
      keratins and point mutations in keratins 5 and 14. Clumping of basal cell
      keratins is pathognomonic of EB Dowling-Meara and caused by mutations in hot
      spots of the rod domain of K5 and K 14. Clumps and aggregates of basal keratins
      occur side by side in the same cell and thus do not indicate specific different
      types of mutations. Similar clumping of suprabasal keratins in bullous CIE Brocq
      and in palmoplantar keratoderma Voerner have been assigned to identical types of
      mutations in the same critical position of the rod domain in K 1, K 10, and K 9,
      respectively. Highly unusual tubular keratins are pathognomonic of another
      dominant palmoplantar keratoderma type the genetic basis of which still awaits
      elucidation. Shell formation of (low molecular weight?) keratins in ichthyosis
      hystrix Curth-Macklin is not linked to the keratin gene clusters on chromosomes
      12 and 17 and might be related to regulatory genes of keratin expression.
      Suprabasal shells in congenital reticular ichthyosiform erythroderma do not
      consist of keratins but resemble glycoprotein networks. Finally, the keratohyalin
      abnormality in ichthyosis vulgaris was the clue for the identification of a
      filaggrin deficiency, at the same time giving evidence to the heterogeneity of
      keratohyalin proteins.

PMID- 7525740
TI  - Annual meeting of the International Society for Interferon and Cytokine Research.
      ISICR '94. Budapest, Hungary, October 2-7, 1994. Abstracts.

PMID- 7525741
TI  - Local tolerance to subcutaneous infusions of high concentrations of
      hydromorphone: a prospective study.
AB  - In a prospective open study, 24 patients with cancer pain receiving parenteral
      opioids were administered highly concentrated solutions of hydromorphone in order
      to assess the local tolerance to the subcutaneous infusion. Patients received a
      mean concentration of hydromorphone of 30 +/- 15 mg/mL at a mean rate of infusion
      of 0.3 +/- 0.25 mL/hr. Of 22 evaluable patients, 17 (77%) had a site duration of
      more than 7 days with their first subcutaneous site (mean concentration of 34 +/-
      8 mg/mL of hydromorphone). Four of the five remaining patients (80%) had site
      duration of more than 7 days with their second subcutaneous site. Only one
      patient (5%) did not reach a 7-day duration after three consecutive site changes.
      Out of 7 subcutaneous sites that presented signs of toxicity before 7 days of
      infusion, the main problem was erythema in three cases, swelling in two cases,
      and bleeding in two cases. All sites improved spontaneously and did not require
      any medical treatment. No correlation was found between the concentration or rate
      of infusion of hydromorphone and the duration of the subcutaneous site. The
      duration of the site was significantly correlated with weight, tricep skinfold,
      subscapular skinfold, and age of the patients. Our findings suggest that
      hydromorphone can be safely administered in concentrations that are much higher
      than those commercially available. The availability of highly concentrated
      formulations of different opioids for parenteral use will make home management
      simpler and cheaper.

PMID- 7525742
TI  - Preface: pain medicine and addiction medicine--controversies and collaboration.

PMID- 7525743
TI  - Addiction in the treatment of pain: significance, recognition, and management.
AB  - The treatment of pain in the presence of addiction is often a challenge. Better
      understanding of the relationships between pain and addictive disease may help
      both pain clinicians and addictionists treat individuals in whom these conditions
      coexist. Mechanisms through which addiction may reinforce pain are explored. The
      identification of addictive disease in the pain treatment setting is discussed.
      Strategies for effective management of pain in individuals with addictive disease
      are suggested.

PMID- 7525745
TI  - Prescription of opioids for treatment of pain in patients with addictive disease.
AB  - Addiction medicine specialists and pain specialists can provide better patient
      care by combining their expertise when treating patients who are addicted to
      alcohol, street drugs, or prescription medications. Addiction specialists-
      particularly those whose primary treatment philosophy is drug free--must accept
      that controlled opiate maintenance is appropriate for some patients, and pain
      specialists need to increase their sensitivity to the possibility of addiction
      among their patients. Both pain and addiction are treatable conditions, and
      optimal care of some patients requires the coordinated services of both an
      addiction medicine specialist and a pain specialist.

PMID- 7525744
TI  - Long-term use of opioid analgesics for the treatment of chronic pain of
      nonmalignant origin.
AB  - The use of long-term opioids (LTOs) to treat chronic pain of nonmalignant origin
      (CNMP) is controversial. Most physicians had felt there was essentially no role
      for LTOs in CNMP, but successful treatment outcomes have recently been reported.
      Tolerance, organ toxicity, or fear of addiction are not reasons to limit LTOs.
      The significant question is efficacy. Does LTO therapy improve pain and increase
      function with minimal side effects or risk? It is useful to divide chronic pain
      patients into three types. Type 1 patients are "typical" chronic pain patients
      with pain and disability far out of proportion to the peripheral stimulus.
      Psychological factors are significant. In this type of patient, opioids appear to
      do more harm than good. Type 2 patients have ongoing nociception and moderate
      refractory pain. Type 3 patients have refractory severe nociception or
      neuropathic pain. The latter types might be considered for LTOs. LTO use is
      appropriate for a very small, carefully selected group of patients.

PMID- 7525746
TI  - Opioids, chronic pain, and the law.
AB  - As the United States continues its "War on Drugs," physicians who prescribe
      opioids for the purpose of pain control must recognize that legal issues are an
      important part of the prescription process. Physicians who do not correctly
      prescribe opioids may mark their patients as drug abusers and themselves as
      misprescribers. Efforts are under way to characterize appropriately the
      conditions under which opioids should be prescribed for the management of pain.
      California and Texas have passed intractable pain laws, which permit the
      prescribing of opioid medication for chronic pain patients. These laws were
      necessary because claims were made against prescribers who legitimately
      administered opioids to chronic pain patients. Physicians must be aware that once
      a patient has been diagnosed an addict, it is not legal to prescribe opioids for
      the purpose of maintaining or detoxifying that patient; treatment of pain is
      still permissible, however. It is clear that new standards of care must be
      developed to reduce the liability of legitimate prescribers from sanctions in
      either criminal or civil settings. With new standards of care, prescriptions for
      opioids written in good faith for the treatment of pain should survive legal
      scrutiny.

PMID- 7525747
TI  - Prescribing practices of a palliative care service.
AB  - We describe the prescribing pattern for ambulatory patients of a Palliative Care
      Service in a tertiary care medical center. We audited 81 outpatient medication
      records to describe the drugs required for symptom control in patients with
      advanced cancer; 17 therapeutic drug classifications were used. The most
      frequently prescribed drug classes were analgesics, followed by laxatives and
      antiemetics. Individual drugs most commonly used were morphine, docusate sodium,
      and ranitidine. Symptom control in a multisymptomatic population can be achieved
      with a limited number of drugs. Education of physicians and nurses in the
      therapeutics of palliative care should focus on the indications, efficacy, and
      side effects of commonly used effective drugs.

PMID- 7525748
TI  - World Health Organization-International Association for the Study of Pain: joint
      initiatives in Cancer Pain Relief.

PMID- 7525749
TI  - Educational programs in pain and palliative care.

PMID- 7525751
TI  - Strategies for improving cancer pain management.

PMID- 7525750
TI  - Availability of opioids for cancer pain: recent trends, assessment of system
      barriers, New World Health Organization guidelines, and the risk of diversion.

PMID- 7525752
TI  - Palliative care in Latin America.
AB  - During the last 5 yr, a number of palliative care programs have been developed in
      Latin America. All these programs benefit from the strong personal motivation of
      leaders who commit a considerable amount of their own time and resources to the
      success of their programs. Financial problems, the lack of adequate knowledge of
      pain control and other palliative care issues, difficulties in communication and
      obstacles related to local legislation are common to all programs, although each
      group has dealt with these problems in different ways. International programs
      have helped in the development of many of the local leading groups. Improved
      communication between different local groups, national governments, and
      international WHO Collaborating Centers will, hopefully, further promote the
      development of palliative care in Latin America in years to come.

PMID- 7525753
TI  - Palliative care in Europe.

PMID- 7525755
TI  - The Oncology Nursing Society: commitment and activities promoting cancer pain
      relief.
AB  - The primary mission of the ONS is promoting excellence in oncology nursing. In
      its efforts to accomplish this mission, the undertreatment of cancer pain has
      emerged as a significant issue for clinicians, educators, researchers, and
      administrators involved in the care of people with cancer. In an effort to
      promote cancer pain relief, the ONS contributes human, administrative, and
      financial resources from its existing organizational structure, personnel, and
      volunteers in the variety of ways described above. The structure of the ONS
      enables it to support the goal of cancer pain relief from the broadest of policy
      making activities nationally to the provision of care by a nurse to a patient and
      family. The ONS Position Paper on Cancer Pain, other position papers and
      statements, adopted resolutions, and the strategic planning process will continue
      to guide the ONS's commitment and contributions to promoting cancer pain relief.

PMID- 7525756
TI  - Patient advocacy in cancer pain relief: the Cancer Care model.

PMID- 7525754
TI  - State cancer pain initiatives.
AB  - Interest and participation in state cancer pain initiatives have grown rapidly in
      the past 5 yr. Of signal importance to these state efforts is the fact that
      several national groups have made relief of cancer pain a priority. State cancer
      pain initiatives will play a key role in disseminating basic pain-management
      information, in changing practice and ultimately in evaluating the effectiveness
      of cancer pain control efforts. They are dedicated to making relief of cancer
      pain a reality. That is a challenge that will occupy them for many years to come.

PMID- 7525757
TI  - Argentina: status of cancer pain and palliative care.

PMID- 7525758
TI  - Australia: status of cancer pain and palliative care.

PMID- 7525759
TI  - Canada: status of cancer pain and palliative care.

PMID- 7525760
TI  - China: status of cancer pain and palliative care.

PMID- 7525761
TI  - Colombia: status of cancer pain and palliative care.

PMID- 7525763
TI  - Egypt: status of cancer pain and palliative care.

PMID- 7525762
TI  - Costa Rica: status of cancer pain and palliative care.

PMID- 7525764
TI  - France: status of cancer pain and palliative care.

PMID- 7525765
TI  - Germany: status of cancer pain and palliative care.

PMID- 7525766
TI  - Greece: status of cancer pain and palliative care.

PMID- 7525767
TI  - Hungary: status of cancer pain and palliative care.

PMID- 7525769
TI  - Indonesia: status of cancer pain and palliative care.

PMID- 7525770
TI  - Japan: status of cancer pain and palliative care.

PMID- 7525771
TI  - Papua New Guinea: status of cancer pain and palliative care.

PMID- 7525768
TI  - India: status of cancer pain and palliative care.

PMID- 7525772
TI  - The Philippines: status of cancer pain and palliative care.

PMID- 7525773
TI  - Singapore: status of cancer pain and palliative care.

PMID- 7525775
TI  - United States: status of cancer pain and palliative care.

PMID- 7525774
TI  - Thailand: status of cancer pain and palliative care.

PMID- 7525776
TI  - Vietnam: status of cancer pain and palliative care.

PMID- 7525777
TI  - Spinal opioids: distinguishing trend from science.

PMID- 7525779
TI  - Second thoracic sympathetic ganglionectomy in sympathetically maintained pain.
AB  - Twenty-four individuals with sympathetically maintained pain were treated by
      posterior paravertebral T2 sympathectomy following transient response to
      sympathetic nerve blockade. Eight surgical patients (33.4%) had causalgia, and 16
      patients (66.4%) suffered with reflex sympathetic dystrophy. Overall, physical
      evidence of improvement was noted in 87% of surgical patients, with subjective
      improvement in 71%. Reflex sympathetic dystrophy patients fared better than those
      with causalgia. Complications were minor. The techniques employed appear safe and
      effective; a multidisciplinary approach with neurosurgery, physiatry,
      anesthesiology, psychology, and allied health services is recommended.

PMID- 7525778
TI  - Dehydration symptoms of palliative care cancer patients.
AB  - A cross-sectional survey of inpatient palliative care subjects (n = 52) was
      performed to determine the severity and distribution of symptoms thought to be
      associated with dehydration in terminally ill cancer patients and to clarify the
      association between the severity of these symptoms and commonly used objective
      measures of dehydration. Each patient rated the severity of seven symptoms using
      100-mm visual analogue scales. The symptoms considered were thirst, dry mouth,
      bad taste, nausea, pleasure in drinking, fatigue, and pain. Associations were
      sought between these symptoms and predictor variables (fluid intake, plasma
      osmolality, sodium, and urea) and confounding variables (age, medications, oral
      disease, and mouth-care regimen). Mean symptom ratings were thirst 53.8 mm, dry
      mouth 60.0 mm, bad taste 46.6 mm, nausea 24.0 mm, pleasure in drinking 61.6 mm,
      fatigue 61.8 mm, and pain 33.5 mm. Using multiple-linear regression, no
      association could be demonstrated between thirst (the principal outcome of
      interest) and the predictor or confounding variables. Estimates of the study
      power performed after completion revealed a 76% chance of detecting a 20-mm
      difference between high and low fluid intake groups. This study provides the
      first quantitative estimate of the experience of dehydration symptoms in those
      with advanced cancer. The symptoms appear to be rated moderately severe, but
      there is no demonstrable association between severity and fluid intake. Further
      studies with greater statistical power and more accurate hydration assessment
      would strengthen our understanding of this association.

PMID- 7525780
TI  - Myoclonic spasms following intrathecal diamorphine.
AB  - The use of intrathecal diamorphine via an implanted portal system is described
      for pain control in a patient suffering from vertebral metastatic disease. The
      complication of myoclonic spasms affecting the lower half of the body occurred
      after 14 days, when increasing the bolus dose to 40 mg. The spasms lasted for 3
      hr and then gradually subsided. Diamorphine was subsequently restarted at a lower
      dose of 15 mg twice daily. On increasing the dose to 20 mg diamorphine 10 days
      later, severe distressing myoclonic spasms recurred 20 min postinjection.
      Myoclonus could only be controlled by instituting a local anesthetic intrathecal
      block. The patient was finally managed with 20 mg diamorphine per day by
      intrathecal infusion, and the pain was reasonably well controlled for the
      following 10 weeks without any recurrence of myoclonic spasms.

PMID- 7525781
TI  - Interpleural analgesia for the treatment of severe cancer pain in terminally ill
      patients.
AB  - Interpleural analgesia was used to alleviate acute, severe exacerbations of
      chronic pain unrelieved by pharmacologic therapy in ten terminally ill cancer
      patients. Pain from metastatic disease to the neck, arms, chest, brachial plexus,
      thorax, or abdomen was effectively eliminated between 7 hr and 40 days in nine
      patients, who died with minimal or no pain. The technique was performed primarily
      using bupivacaine. No side effects were detected. Interpleural analgesia appears
      to be effective in rapidly controlling acute exacerbations of cancer pain in
      terminally ill patients. Moreover, it may also be a suitable therapy for moribund
      patients when used as a continuous-infusion technique.

PMID- 7525782
TI  - Use of the Edmonton Injector for parenteral opioid management of cancer pain: a
      study of 100 consecutive patients.
AB  - In this retrospective study, we reviewed the patterns of use of the Edmonton
      Injector (EI) in 100 consecutive cancer patients. Seventy-eight patients used the
      EI for an average of 23 +/- 27 days. The main reasons for starting the EI were
      nausea (37 patients) and severe pain (31 patients). The median opioid dose
      equivalent to parenteral morphine (MEDD) was 264 +/- 443 mg/day. The mean
      duration of the subcutaneous injection site was 6.5 +/- 9.2 days. The most
      frequent reasons for change were accidental needle pulling (59%) and erythema
      (12%). Only two patients developed local infection (1% of 196 sites). The average
      cost of treatment was $1.65 Canadian per patient per day. No mechanical problems
      or refusals to start or continue treatment were detected. We conclude that the EI
      is a safe and simple device that allows for cost-effective parenteral
      administration of opioids for cancer pain.

PMID- 7525783
TI  - Intrathecal infusional analgesia for nonmalignant pain: analgesic efficacy of
      intrathecal opioid with or without bupivacaine.
AB  - We report on the analgesic efficacy of intrathecal infusions of opioids alone or
      in combination with bupivacaine in 16 nonmalignant pain patients with implanted
      pumps. Three patients had nociceptive pain, five had neuropathic pain, and 8 had
      mixed pain syndromes. Infusional therapy was delivered over a combined monthly
      total of 445 mo of therapy (mean, 27.8 mo). Dose requirements appeared to be
      stable with a mean dose increase of 0.26 mg/mo. Bupivacaine was added to the
      opioid to enhance pain control in 13 patients who received combination therapy
      for an average of 11.7 mo/patient. Thirteen patients (81%) reported good to
      excellent results with opioid alone or opioid combined with bupivacaine. The
      addition of bupivacaine improved analgesia in two of three patients with
      nociceptive pain (66.7%), compared to eight of ten patients with a pure or mixed
      neuropathic component to their pain (80%). We conclude that intrathecal opioids
      alone or in combination with bupivacaine are efficacious for the treatment of
      nonmalignant pain states and are relatively free of significant side effects or
      tolerance.

PMID- 7525784
TI  - The pain resource nurse training program: a unique approach to pain management.
AB  - Adequate pain management is a 24 hr a day responsibility for health-care
      professionals working with cancer patients. Because nurses spend more time with
      patients in pain than any other member of the health-care team, they play a
      central role in pain assessment and pain management. The City of Hope National
      Medical Center, a clinical cancer center, developed a pain management course for
      staff nurses entitled "The Pain Resource Nurse (PRN) Training Program." The
      purpose of this innovative course was to prepare staff nurses to assume an active
      role in pain management. Twenty-six registered nurses participated in the 40-hr
      didactic and clinical course. The curriculum included information on pain
      assessment, pharmacology, nondrug interventions, and cultural, ethical, and
      psychosocial issues related to pain. After completion of the course, program
      staff have remained available to the PRNs to provide current information on pain
      management, and to assist with role implementation and guidance on interfacing
      with staff. This paper reports on the development, implementation, and 3-mo
      evaluation of this unique program.

PMID- 7525785
TI  - Cancer pain relief in India.

PMID- 7525786
TI  - Cancer pain relief in Canada.

PMID- 7525787
TI  - Cancer pain relief in Greece.

PMID- 7525788
TI  - Fear and greed: the commercialization of palliative medicine.

PMID- 7525789
TI  - The role of octreotide in palliative care.
AB  - Octreotide, an analogue of somatostatin with a more favorable pharmacokinetic
      profile, is a new drug that may offer some advantages in the palliative care
      setting. It has been used with favorable results in the management of some
      gastrointestinal disorders, such as gastrointestinal hemorrhage, diarrhea, short
      bowel syndrome, fistula, and intestinal occlusion in the palliative care setting.
      These favorable results occurred without important side effects, underlining the
      potential role of this drug. The cost-benefit ratio of this expensive drug must
      be considered, however.

PMID- 7525790
TI  - Chemotherapy combined with or without hyperthermia for patients with oesophageal
      carcinoma: a prospective randomized trial.
AB  - From 1990 to 1991, 40 patients with squamous cell carcinoma of the thoracic
      oesophagus were admitted to our institutions and chemotherapy (oil Bleomycin p.o.
      and CDDP d.i.v.) either combined with or without hyperthermia was performed, in a
      prospective randomized trial carried out to investigate the effects of
      hyperthermia. The two groups (group A, consisting of 20 patients given
      chemotherapy alone; and group B, made up of 20 given chemotherapy with
      hyperthermia) were comparable with regard to various prognostic factors.
      Following the above treatment regimens, an oesophagectomy was done in 16 and 17
      patients from groups A and B, respectively. A subjective improvement of dysphagia
      was seen in 8 (40.0%), and in 14 patients (70.0%), while a radiographic
      improvement was recognized in 5 (25.0%) and 10 cases (50.0%) in groups A and B,
      respectively. In the resected specimen of 16 (group A) and 17 patients (group B),
      histopathological evidence of the effectiveness of the treatments were recognized
      in 3 (18.8%) and 7 (41.2%) from groups A and B, respectively. Excluding the cases
      of superficial carcinoma (T1 tumour), histologic effectiveness of the treatments
      were recognized in 2 (14.3%) and 7 (58.3%) in groups A and B, respectively (p <
      0.05). There was no difference in the occurrence of side effects between the
      groups. Therefore, the clinical and pathological effects were favourable in the
      hyperthermia combined with chemotherapy group, especially in the cases with
      advanced oesophageal cancer.

PMID- 7525791
TI  - [Determinants of homologous blood utilization in addition to autologous blood
      transfusion--a multivariate study].
AB  - Since April 1989, we have been using autologous blood donation in order to avoid
      homologous blood transfusion as much as possible. To determine the factors which
      influence the necessity for homologous blood transfusion as well as autologous
      blood donation. Of them 77.6% (group 1) required autologous blood only, but
      others needed homologous blood transfusion as well as autologous blood. Using an
      invert analysis, preoperative factors that showed significant differences were
      age, body weight, number of autologous blood donations, amount of donated
      autologous blood, preoperative Hb and Ht. Among operative factors, aortic cross
      clamping time, cardiopulmonary bypass time, amount of concentrated blood from CPB
      circuit, amount of transfused autologous blood and amount of drainage
      demonstrated significant differences between groups. Univariately significant
      factors were studied by multivariate discriminant analysis. Total amount of
      drainage proved to be the best contributor of non-homologous blood transfusion
      surgery, followed by preoperative Hb, body weight, amount of concentrated blood
      from CPB circuit and amount of donated autologous blood in order of contribution
      Understanding these factors, homologous blood transfusion requirement may be
      greatly reduced. This is thought to be the largest series of autologous blood
      donation in Japan.

PMID- 7525793
TI  - [Concomitant operation of CABG and splenectomy following high-dose transvenous
      gamma-globulin therapy in a patient with idiopathic thrombocytopenic purpura--a
      case report].
AB  - A 60-year-old man with effort angina and idiopathic thrombocytopenic purpura
      (ITP) underwent concomitant operation of coronary artery bypass grafting (CABG)
      and splenectomy. High-dose transvenous gamma-globulin therapy (400 mg/kg/day) was
      performed for five days before surgery. The platelet count increased from 1.4 X
      10(4)/mm3 to 8.7 X 10(4)/mm3. CABG was performed immediately followed by
      splenectomy. This is the first case with concomitant operation of cardiac surgery
      and splenectomy which was safely performed after high-dose transvenous gamma
      globulin therapy.

PMID- 7525792
TI  - [A case of yolk sac tumor of the anterior mediastinum].
AB  - A 26-year-old male was clinically diagnosed as having a anterior mediastinal yolk
      sac tumor because of the elevation of the serum AFP (26,765 ng/ml) and a large
      mass lesion (13 x 12 x 8 cm) in the anterior mediastinum and right thoracic
      cavity. After three courses of chemotherapy with CDDP and VP-16, the mediastinal
      mass reduced in size significantly but the serum AFP level did not reach within
      normal range. We suspected that the tumor took a resistance to drugs, accordingly
      the operation was performed. The tumor was completely removed and there were
      small viable foci of the tumor in part of the tumor. The histological examination
      revealed the findings of yolk sac tumor. After the operation, the serum AFP level
      decreased within normal range. He is alive without evidence of recurrence during
      18 months after operation. It was noticed that the serum AFP is a useful
      indicator for determining the chance of operation after chemotherapy.

PMID- 7525794
TI  - A meta-analysis of randomized placebo control trials in Fontaine stages III and
      IV peripheral occlusive arterial disease.
AB  - In patients with Fontaine Stage III and IV POAD unsuitable for arterial
      reconstruction, Iloprost, a prostacyclin analogue, has been shown in six RCTs to
      have a significant (p < 0.05) beneficial effect with regards to the probability
      of being alive with both legs at six months follow-up. Iloprost has significant
      (p < 0.05) beneficial effects over placebo on ulcer healing and pain relief, but
      these were relatively soft endpoints to study when side effects may have
      unblinded many observers and patients. Further studies are indicated to
      investigate the possible benefit of repeated courses of treatment with Iloprost
      in patients with non-reconstructable Fontaine Stage III and IV POAD as well as
      studies looking at patients who may be suitable only for relatively high risk
      reconstructions. Meta-analysis of all other RCTs of pharmacotherapeutic agents in
      patients with Fontaine Stage III and IV POAD showed no significant benefit over
      placebo for any of the endpoints reported.

PMID- 7525795
TI  - Relapse rates in patients treated with dapsone monotherapy and combinations of
      dapsone and thiambutosine, thiacetazone, isoniazid and streptomycin in the pre
      MDT era.
AB  - Relapse rates were studied in patients from northern Thailand who were started on
      dapsone monotherapy between 1949 and 1976. Included are a group of patients who,
      for various reasons, also received combinations of dapsone and thiambutosine,
      thiacetazone, isoniazid and streptomycin. The overall relapse rate in
      paucibacillary patients on dapsone monotherapy only was 2.7 per 1000 person-years
      at risk (PYR) (average observation period 13.9 years). In the multibacillary
      patients who received dapsone monotherapy only, the relapse rate was 10.5 per
      1000 PYR (average observation period 12.4 years). In both groups it was found
      that 50% of the relapses occurred after the seventh year of follow up. The
      overall relapse rate in those patients whose treatment included thiambutosine,
      thiacetazone, isoniazid and/or streptomycin for at least 3 months was 17.9 per
      1000 PYR (average observation period 11.9 years). The difference with the
      multibacillary patients treated with dapsone monotherapy only is not significant.
      It is concluded that alternative antileprosy drugs included in therapy regimens
      with dapsone in the pre-MDT era did not result in relapses occurring less often.

PMID- 7525796
TI  - [Immunohistochemical localization of transforming growth factor-beta 1 in growth
      plate freshly transplanted into a full-thickness defect in articular cartilage].
AB  - Transplants of the epiphyseal growth plate obtained from the proximal tibia of
      Lewis rats at 3 weeks of age were inserted into full-thickness defects in the
      patellofemoral articular surface of Lewis rats at 5 weeks of age. As controls,
      similar surface defects were induced but no transplants were inserted.
      Transplants were studied immunohistochemically at varying intervals up to 72
      weeks in order to determine the effects of transforming growth factor-beta 1 (TGF
      beta 1) on the repair of the articular cartilage by the epiphyseal growth plate.
      TGF-beta 1 was present in chondrocytes in the region corresponding to the
      hypertrophic zone of the transplanted growth plate at 1 week after
      transplantation. The distribution pattern of TGF-beta 1 in this hypertrophic zone
      was similar to that prior to transplantation. At 2 weeks after transplantation,
      TGF-beta 1 was detected in the matrix, but the hypertrophic chondrocyte cell
      membranes were not clear. TGF-beta 1 was undetectable in the transplanted growth
      plate at 4 weeks after transplantation, at which time a morphological examination
      revealed metaplastically-transformed articular cartilage but no hypertrophic
      cartilage cells. No immunostaining of TGF-beta 1 was present in the untreated
      articular defect. These findings suggested that TGF-beta 1 in the hypertrophic
      chondrocytes was probably transferred from the cytoplasm to the extracellular
      matrix and stimulated the ossification of the matrix with vessel induction and
      osteoid formation during the process of incorporation of the transplant into the
      articular cartilage defect.

PMID- 7525797
TI  - [Hepatitis C antibody and HCV-RNA].

PMID- 7525798
TI  - [Interferon therapy of chronic hepatitis B].

PMID- 7525799
TI  - [Interferon therapy of hepatitis C].

PMID- 7525800
TI  - [Present status of developing hepatitis C vaccines].

PMID- 7525801
TI  - [Problems on interferon therapy of chronic hepatitis C].

PMID- 7525802
TI  - [Therapy of chronic non-active hepatitis].

PMID- 7525803
TI  - [Therapy of chronic hepatitis. Discussion].

PMID- 7525804
TI  - [Case of acute kidney failure induced low-molecular weight dextran effectively
      treated by plasma exchange].

PMID- 7525806
TI  - [Chronic myelocytic leukemia].

PMID- 7525805
TI  - [Case of thrombotic thrombocytopenic purpura treated with plasma exchange and
      immunoglobulin therapy].

PMID- 7525807
TI  - [Malignant lymphoma].

PMID- 7525810
TI  - [Basic facts and clinical application of hematopoietic factors].

PMID- 7525809
TI  - [Genetic (DNA or RNA) diagnosis of infections].

PMID- 7525808
TI  - [Hematopoietic factors: cytokine].

PMID- 7525811
TI  - [Clinical study of drug-induced pneumonitis].

PMID- 7525812
TI  - [Autopsy case of plasma cell granulomas of meninges with difficulty of the
      diagnosis].

PMID- 7525813
TI  - [New therapy of patients with malignant lymphoma using G-CSF].

PMID- 7525814
TI  - [Treatment of adult T-cell leukemia-lymphoma].

PMID- 7525815
TI  - Molecular mechanism of interleukin-8 gene expression.
AB  - A potent leukocyte chemotactic and activating cytokine, interleukin-8 (IL-8), is
      produced by numerous types of cells in response to inflammatory stimuli.
      Accumulating evidence indicate that the transcription of IL-8 gene requires the
      activation of either the combination of NF-kappa B and AP-1 or that of NF-kappa B
      and NF-IL6, depending on the type of cells. Alternatively, the activation of NF
      kappa B is indispensable for IL-8 gene activation in any types of cells examined.
      On the other hand, an immunosuppressant, FK506, and a glucocorticoid inhibit the
      gene transcription as well as the production of IL-8. Molecular analyses of IL-8
      gene repression by these agents revealed that both affected the activity of the
      transcription factor(s) bound to the NF-kappa B site, albeit in different ways,
      thereby suppressing IL-8 gene transcription. Collectively, IL-8 production seems
      to be controlled mainly at the activation step of the transcription factor(s)
      bound to the NF-kappa B site.

PMID- 7525817
TI  - Induction of superoxide anion production from monocytes an neutrophils by
      activated platelets through the P-selectin-sialyl Lewis X interaction.
AB  - Activated platelets expressing P-selectin on their surface are known to adhere to
      monocytes and neutrophils. We examined the possibility that the leukocytes were
      activated by their adhesion to activated platelets and demonstrated that P
      selectin-dependent platelet adhesion to neutrophils and monocytes induced
      production of extracellular superoxide anion (O2-) by these leukocytes. Leukocyte
      membrane glycoproteins containing Ser/Thr-linked carbohydrate chains were
      responsible for the signal reception leading to the leukocyte activation.
      Cytokines were shown to influence these processes. For example, treatments of
      neutrophils with interleukin-8 (IL-8) or granulocyte colony-stimulating factor (G
      CSF) potentiated the P-selectin-induced O2- production. Furthermore, interleukin
      1 (IL-1) and interferon-gamma (IFN-gamma) induced surface expression of P
      selectin on platelets in the presence of a low concentration of thrombin and
      consequently enhanced their adhesion capacity to leukocytes. These results
      indicated that the adhesion of activated platelets to the leukocytes through the
      interaction between P-selectin and its carbohydrate ligand, sialyl Lewis X (LeX),
      was a crucial step for the activation of leukocyte function and supported the
      notion that activated platelets were actively involved in the inflammatory
      processes.

PMID- 7525816
TI  - The high-output nitric oxide pathway: role and regulation.
AB  - Nitric oxide synthase (NOS) catalyzes the production of nitric oxide (NO), a
      short-lived radical gas with physiological or pathophysiological roles in nearly
      every organ system. The inducible NO synthase (iNOS) is a high-output isoform
      compared to the two constitutive NOSs. The iNOS from murine macrophages tightly
      binds calmodulin as a subunit, and its activity is not dependent on exogenous
      calmodulin or elevated calcium. This iNOS is induced at the transcriptional level
      by bacterial lipopolysaccharide (LPS) and interferon-gamma. The promoter region
      of the murine iNOS gene contains at least 24 oligonucleotide motifs corresponding
      to elements involved in the binding of transcription factors in the promoters of
      other cytokine-inducible genes. Nuclear factor NF-kappa B/c-rel, interacting with
      cycloheximide-sensitive protein(s) and binding to the NF-kappa Bd site in the
      iNOS promoter, controls the induction of iNOS by LPS. However, iNOS is also
      regulated posttranscriptionally. Complex regulation of iNOS at multiple levels
      may reflect the dual role of iNOS in host defense and autotoxicity.

PMID- 7525818
TI  - Hyaluronan receptor (CD44) expression and function in human peripheral blood
      monocytes and alveolar macrophages.
AB  - CD44 glycoproteins are present on the surfaces of many hematopoietic cells and in
      some cases can bind hyaluronan, a major component of the extracellular matrix. In
      the present study, we have found that newly explanted human peripheral blood
      monocytes (PBMs) exhibit a major CD44 band of 85 kDa, whereas autologous alveolar
      macrophages (AM phi) express multiple isoforms ranging from 85 to 200 kDa. Within
      4 h in culture, PBMs began expressing new CD44 isoforms of 120, 150, and 180 kDa.
      Newly explanted AM phi specifically bound [3H]hyaluronan (135 cpm/microgram
      protein), but newly explanted PBMs did not. However, in vitro cultured PBM
      progressively acquired the ability to bind [3H]hyaluronan and exhibited specific
      binding of hyaluronan similar to that of AM phi (113 cpm/microgram protein) after
      4 days in culture. In both case, the binding of [3H]hyaluronan was specifically
      inhibited by the addition of monoclonal antibody directed against CD44. AM phi
      readily degraded [3H]hyaluronan and reached a plateau after 4 days in culture
      (115 cpm/microgram protein). Newly explanted PBM exhibit no hyaluronan
      degradation and only a small degradative activity after 4 days in culture (6 to
      11 cpm/microgram protein). Thus, CD44 expression and function appear to change as
      PBM mature in vitro resembling more that found in AM phi.

PMID- 7525819
TI  - Delivery of exogenous antigen into the major histocompatibility complex class I
      and class II pathways by electroporation.
AB  - Exogenous, nonreplicating protein antigens (Ags) are usually taken up by antigen
      presenting cells (APCs) via endocytosis or pinocytosis and enter the major
      histocompatibility complex (MHC) class II processing and presentation pathway.
      Although exogenous Ags are not processed and presented in the class I pathway by
      most cells, soluble proteins can enter the class I processing and presentation
      pathway if they are introduced directly into the cytoplasm of APCs. The purpose
      of these studies was to determine whether exogenous proteins could be processed
      and presented to T cells if they were delivered into cells by electroporation.
      The conditions for electroporation were optimized so that the viability of the
      electroporated cells was high, and the majority of electroporated cells had
      protein incorporated. Electroporated B cells not only presented exogenous
      ovalbumin to CD8+, class I MHC-restricted T cells but also stimulated CD4+, class
      II MHC-restricted T cells. Electroporated cells also primed Ag-specific cytotoxic
      T lymphocytes (CTLs) in vivo, stimulated CTL precursors in vitro, and served as
      target cells for lysis by Ag-specific CTLs, indistinguishable from transfected
      cells. Thus, electropermeabilized cells were structurally intact, and the
      introduced exogenous protein was processed and presented in association with both
      class I and class II MHC molecules. This approach is as efficient and
      reproducible as other techniques of delivering exogenous proteins into the
      intracellular processing pathways. These studies suggest that electroporation
      could be employed for the study of cell-mediated immunity to various exogenous
      proteins.

PMID- 7525820
TI  - Cross-linking of CD18 in human neutrophils induces an increase of intracellular
      free Ca2+, exocytosis of azurophilic granules, quantitative up-regulation of
      CD18, shedding of L-selectin, and actin polymerization.
AB  - Polymorphonuclear leukocytes (PMNs) exert most of their physiological functions
      while adherent to surfaces rather than in suspension. PMN adhesion is largely
      dependent on the function of the beta 2 integrins, CD11a,b,c/CD18. We mimicked
      engagement of beta 2 integrins by antibody cross-linking of CD18 on isolated
      human PMNs using both intact monoclonal antibody and F(ab')2 fragments. Within
      seconds of CD18 cross-linking, we observed a significant, transient rise of
      intracellular free Ca2+ concentration by 200-300 nM, which was largely due to
      Ca2+ mobilization from intracellular stores. The Ca2+ signal was blocked after
      pretreatment with phorbol myristate acetate, an activator of protein kinase C,
      but not with herbimycin A, a potent inhibitor of tyrosine kinases. In addition to
      the rise of intracellular free Ca2+ concentration, CD18 cross-linking induced
      exocytosis of azurophilic granules (release of 26% of total PMN elastase), which
      was significantly inhibited by herbimycin A. Moreover, 2.2-fold up-regulation of
      CD18 antigen and significant down-regulation of surface expression of the
      granulocyte adhesion molecule L-selectin were induced. Granulocyte F-actin
      content as measured by nitrobenzoxadiazole-phallacidin increased significantly 1
      min after CD18 cross-linking. By contrast, CD18 cross-linking by soluble
      antibodies did not induce superoxide production, but PMNs bound to immobilized
      monoclonal antibodies against CD18 released significant amounts of superoxide.
      Initial signaling through beta 2 integrins does not appear to be mediated by a
      phospholipase C isoform activated through tyrosine phosphorylation, because the
      Ca2+ signal was not altered by herbimycin A. However, more complex cellular
      responses including exocytosis were found to require tyrosine phosphorylation. We
      show that engagement of beta 2 integrins provides an important stimulatory signal
      to PMNs inducing degranulation, modulation of L-selectin, and cytoskeletal
      changes.

PMID- 7525821
TI  - Lipoprotein lipase (LpL) affects low density lipoprotein (LDL) flux through
      vascular tissue: evidence that LpL increases LDL accumulation in vascular tissue.
AB  - A cardinal feature of the atherosclerotic lesion is increased low density
      lipoprotein (LDL) content of the arterial wall. Such increases in vascular wall
      LDL could result from either increased flux of circulating LDL across the
      arterial endothelial barrier or decreased efflux of LDL that has entered the
      vascular tissue. A number of studies have focused on factors that alter
      permeability of endothelial cell monolayers and intact blood vessels causing
      increased LDL influx. In contrast, the current studies were designed to test the
      hypothesis that lipoprotein lipase (LpL), increases LDL accumulation and
      decreases LDL efflux from vascular tissue. Frog mesenteric venular microvessels
      were cannulated and the rates of fluorescently labeled LDL accumulation (N/t) and
      efflux (T1/2) were measured by quantitative fluorescence microscopy. When the
      vessels were perfused with a solution containing bovine milk LpL (10(-5) g/ml)
      and human LDL (protein = 0.68 mg/ml), N/t was > 15x greater than that of control
      vessels which were perfused with LDL alone. LpL addition did not change albumin
      permeability, suggesting that increased N/t was not related to changes in vessel
      permeability. Increased LDL accumulation within the vessel could have resulted
      from either an increase in LDL influx from the vessel lumen into the vascular
      tissue or a decrease in efflux of LDL. Therefore, LDL efflux from vascular tissue
      was determined by measuring the rate of decline in fluorescence intensity of
      control and LpL-treated vessels after washout of the vessel lumen with a clear,
      nonfluorescent solution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525823
TI  - Effects of a polyclonal antiserum to rat growth hormone on circulating insulin
      like growth factor (IGF)-I and IGF-binding protein concentrations and the growth
      of muscle and bone.
AB  - A polyclonal antiserum to rat GH (anti-rGH) injected into rats for 3 or 8 weeks
      markedly reduced the weight, total protein and RNA content of muscles of the hind
      limb. These effects were prevented when bovine GH (bGH) was administered
      simultaneously. In a second experiment, the effects of 8 weeks of treatment with
      anti-rGH on the growth of the whole body, muscle and bone were investigated. Body
      weights of rats were decreased by 58% by treatment with anti-rGH; muscle weights
      were reduced by slightly more than the decrease in body weight (by 64%, 65% and
      61% respectively for plantaris, soleus and gastrocnemius). The weight of the
      tibia was decreased by 54%, its length was decreased by 23%, cortical width and
      overall width were reduced by 26% and 18% respectively, suggesting a possible
      role for GH in osteoclastic activity. Serum total insulin-like growth factor-I
      (IGF-I) concentrations were decreased by 80-90% in both experiments by anti-rGH;
      these changes were prevented in the first experiment by concurrent treatment with
      anti-rGH and bGH. The serum IGF-binding protein-3 (IGFBP-3) concentration was
      also decreased by anti-rGH in experiment 1 (by 86%); the response of the 28-32
      kDa IGFBPs was smaller (-35%), and was restored to control values by simultaneous
      injection of bGH. Western immunoblotting using an antiserum to IGFBP-2 showed
      that there was a marked decrease from neonatal to adult stages which was
      independent of anti-rGH treatment. This clearly demonstrated a dissociation of
      the reciprocal relationship supposed to exist between IGFBPs-2 and -3. The 24 kDa
      IGFBP-4 was unaffected by anti-rGH but replacement therapy with bGH doubled its
      concentration. Although the effects on body and muscle weight were prevented when
      rats were given anti-rGH and bGH simultaneously, the possibility of mediation by
      other hormones cannot be precluded.

PMID- 7525822
TI  - The value of serum beta-hCG in the prediction of pregnancy following gamete
      intrafallopian transfer.
AB  - Serum beta-hCG values in 149 GIFT pregnancies obtained on day 14 after oocytes
      retrieval and gamete intrafallopian transfer were evaluated. Mean beta-hCG value
      in multiple livebirths was higher than in the singleton and non-viable pregnancy
      groups and mean beta-hCG value in the latter two groups did not differ from each
      other. Serum beta-hCG level > or = 70 mIU/ml could be a suitable level to predict
      viable pregnancy with 72.8 per cent sensitivity and 92.85 per cent positive
      predictive values.

PMID- 7525824
TI  - Biological effects of prostate specific antigen as an insulin-like growth factor
      binding protein-3 protease.
AB  - Prostate specific antigen (PSA) is an insulin-like growth factor (IGF) binding
      protein-3 (IGFBP-3) protease found in seminal plasma and produced by prostatic
      epithelial cells (PC-E) in vivo. We examined the effects of PSA-proteolysis of
      IGFBP-3 on the affinity of IGFBP-3 fragments for IGFs and on the mitogenic action
      of IGFs on PC-E. Recombinant human IGFBP-3 was cleaved by PSA, then incubated
      with 125I-IGF-I or -II in the presence of varying concentrations of unlabelled
      peptides, and then cross-linking electrophoresis and densitometric analysis were
      performed. While the affinity of IGF-II for the PSA-generated IGFBP-3 fragments
      fell slightly compared to intact IGFBP-3, the affinity of the PSA-generated IGFBP
      3 fragments for IGF-I fell by ten fold. The addition of IGF-I or -II to PC-E in
      serum-free culture conditions resulted in a two-fold stimulation of cell number
      compared to control. The presence of IGFBP-3 in the media blocked the IGF-induced
      stimulation, but had no independent effect in the absence of IGFs. When PSA was
      added to PC-E cultures to which both IGF-I or -II and IGFBP-3 were added, the
      inhibitory effects of IGFBP-3 on IGF mitogenesis were reversed. We conclude that
      PSA decreases the affinity of IGFBP-3 for IGF and can potentiate IGF action in
      the presence of inhibitory IGFBP-3. This phenomenon may contribute to normal and
      malignant prostate growth.

PMID- 7525825
TI  - Placental production of human chorionic gonadotrophin alpha and beta subunits in
      early pregnancy as evidenced in fluid from the exocoelomic cavity.
AB  - Levels of human chorionic gonadotrophin (hCG) and of its free alpha and beta
      subunits were measured using specific immunoradiometric assays in exocoelomic
      fluid (ECF) and maternal serum (MS) collected from five pregnant women at 6.6-8
      weeks of gestation. Mean levels of hCG and its free subunits were significantly
      (P < 0.001) higher in ECF than in MS: 3.5-fold for hCG, 600-fold for free alpha
      hCG and 38-fold for beta hCG. There was no correlation between either hCG levels
      or levels of its free subunits in ECF and MS. On a molar basis, the quantity of
      free alpha hCG subunit expressed as a percentage of the total (free+combined)
      amount was 83% in ECF and 2.7% in MS (P < 0.001). The amount of free beta hCG
      subunit as a percentage of the total was 22% in ECF and 3.5% in MS (P < 0.001).
      The ratio of the total amounts of alpha- and beta hCG subunits amounted to 4.6 in
      ECF and 0.99 in MS (P < 0.001). The heterogeneity of hCG was further investigated
      by polyacrylamide gel electrophoresis followed by immunoblotting. Several bands
      with molecular mass ranging from 42 to 57 kDa, corresponding to hCG dimers, were
      immunodetected in ECF and MS with anti-alpha hCG and anti-beta hCG monoclonal
      antibodies. A free 35 kDa beta hCG immunoreactive band was found in ECF and MS. A
      free alpha hCG immunoreactive band was observed at 23 kDa in ECF and at 21 kDa in
      MS. These findings suggest that the exocoelomic cavity is a reservoir where hCG
      and its subunits produced by trophoblast accumulate directly.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7525826
TI  - The evolution of changes in immunoreactive serum insulin-like growth factors
      (IGFs), IGF-binding proteins, circulating growth hormone (GH) and GH-binding
      protein as a result of short-term dexamethasone treatment.
AB  - Inhibition of growth in man and laboratory animals by glucocorticoid treatment is
      well recognized, yet we have previously shown that glucocorticoids may
      paradoxically enhance GH secretion and increase serum insulin-like growth factor
      (IGF) levels. IGFs circulate bound to high-affinity binding proteins (IGFBPs)
      which modulate their actions, and circulating GH may be associated with two
      binding proteins (GHBPs) of which the high-affinity GHBP has been characterized
      and is structurally identical to the extracellular domain of the GH receptor. We
      have investigated the time-course of changes in GH, IGFs and their binding
      proteins induced by glucocorticoid treatment in normal male volunteers (n = 12,
      age range 22-31 years) sampled at 0800 h daily before and during treatment with
      dexamethasone (2 mg twice daily) for 5 days. In addition, subjects were sampled
      at 30-min intervals over 7-h periods (0730-1430 h) during the day prior to
      dexamethasone (day 0), on day 1 following the first dose of dexamethasone and on
      day 5 following the last dose of dexamethasone. Mean serum IGF-I rose over the
      initial 72 h and remained elevated at 96 h (297 +/- 11.5 compared with basal
      levels of 215.5 +/- 9.3 micrograms/l, P < 0.001) whereas IGF-II levels did not
      change (472.6 +/- 20.5 vs 450.3 +/- 21.7 micrograms/l, P = 0.97). There was a
      concomitant rise in serum IGFBP-3 from basal levels of 3.69 +/- 0.23 mg/l to a
      peak at 5 days of 4.16 +/- 0.21 (P = 0.003 vs day 1).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7525827
TI  - Dexamethasone potentiates the stimulatory effect of insulin-like growth factor-I
      on collagen production in cultured human fibroblasts.
AB  - We examined the effects of insulin-like growth factor-I (IGF-I) and dexamethasone
      on the production of collagen by cultures of human infant foreskin fibroblasts,
      and the interaction between these two factors. IGF-I at 500 ng/ml maximally
      increased collagen accumulation fourfold. Collagen was increased twofold relative
      to total protein production. Dexamethasone at a concentration of 1 mumol/l
      reduced collagen production by between 25% and 40% in unstimulated cells and
      those cultured with up to 100 ng IGF-I/ml. However, dexamethasone did potentiate
      collagen production in cells stimulated with 250 ng IGF-I/ml. This potentiation
      was independent of any effects of IGF-I or dexamethasone on prostaglandin (PG)E2
      production. Transforming growth factor-beta (TGF-beta) is also a potent
      stimulator of collagen formation. However, no potentiation of TGF-beta-stimulated
      collagen production by dexamethasone was apparent. The mechanism by which
      dexamethasone potentiates IGF-I-stimulated collagen production was investigated.
      Dexamethasone treatment increased IGF-I binding to the type 1 IGF receptor
      without altering the binding affinity. Dexamethasone also attenuated the
      secretion of IGF-binding proteins by IGF-I-maintained cells.

PMID- 7525829
TI  - Insulin-like growth factors-I and -II and their binding proteins during postnatal
      development of dwarf Snell mice before and during growth hormone and thyroxine
      therapy.
AB  - The ontogeny of serum insulin-like growth factors (IGFs)-I and -II and their
      binding proteins (IGFBPs) was studied in normal and dwarf Snell mice. IGF-I
      concentrations in serum of normal mice increased between 4 and 8 weeks of age;
      dwarf mice had very low serum IGF-I levels. In both normals and dwarfs, serum IGF
      II levels were highest soon after birth and dropped steadily thereafter. Western
      ligand blots of serum IGFBPs with 125I-IGF-II as tracer revealed the expected
      bands of 41.5, 38.5, 30-32 and 24 kDa. In normal mice the IGFBP-3 doublet was
      already detectable at 2 weeks of age, and its intensity increased with age. In
      dwarf mice the IGFBP-3 doublet was hardly detectable. The changes of IGFs and
      their IGFBPs were studied in sera of dwarf mice after treatment with growth
      hormone (GH) and/or thyroxine (T4) for 4 weeks. In spite of a comparable growth
      response obtained using these hormones, serum IGF-I was increased only by GH
      treatment; a small but significant decrease of serum IGF-II was obtained
      following GH or T4 treatment. An increase of the IGFBP-3 doublet was only
      obtained with GH; T4 and GH + T4 had no effect. The rise of IGFBP-3 after GH
      treatment was accompanied by the formation of the IGFBP 150 kDa complex, as
      measured by neutral gel chromatography. The size distribution of 125I-IGF-II was
      restored to normal, while with 125I-IGF-I only a small peak at 150 kDa was
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525833
TI  - Transduction diversity in olfaction.
AB  - Odors are powerful stimuli that can focus the attention, elicit behaviors (or
      misbehaviors) and even resurrect forgotten memories. These actions are directed
      by the central nervous system, but they depend upon the initial transduction of
      chemical signals by olfactory receptor neurons. Electrophysiological recordings
      suggest that the responses of olfactory receptor neurons to odors are more
      diverse than was initially believed, being mediated by effects on several
      different conductances. Both excitatory and inhibitory responses are produced by
      these effects and some, if not all, odors can affect more than one component of
      the membrane conductance. The extent of this diversity is reviewed here, and its
      impact on our understanding of odor discrimination is discussed.

PMID- 7525831
TI  - Effects of zinc on the kinetics of branchial calcium uptake in freshwater rainbow
      trout during adaptation to waterborne zinc.
AB  - The effects of sublethal waterborne Zn2+ (150 micrograms l-1 = 2.3 mumol-1) on
      the kinetics of unidirectional Ca2+ influx were studied in juvenile freshwater
      rainbow trout during chronic exposure (60 days) at a water [Ca2+] of 1.0 mmol l
      1. An unexposed group held under identical conditions served as control. The
      presence of Zn2+ in the water increased the apparent Km for Ca2+ influx by up to
      300% with only a small inhibitory effect (35% at most) on the maximum rate of
      uptake (Jmax). These results, in combination with earlier data showing that Ca2+
      competitively inhibits Zn2+ uptake, suggest that Zn2+ and Ca2+ compete for the
      same uptake sites. Acute withdrawal of Zn2+ after 3h of exposure resulted in a 23
      fold reduction in Km for Ca2+, but a persistent small depression of Jmax. During
      prolonged exposure to Zn2+, the apparent Km for Ca2+ remained greatly elevated
      and Jmax remained slightly depressed. The actual Ca2+ influx in hard water
      ([Ca2+] = 1.0 mmol l-1) decreased marginally and paralleled the small changes in
      Jmax. The increases in apparent Km had a negligible influence on the actual Ca2+
      influx because Km values (38-230 mumol l-1), even when elevated by Zn2+, remained
      below the water [Ca2+] (1000 mumol l-1). Rainbow trout exposed to Zn2+ exhibited
      a slower rate of protein synthesis in the gills (measured on day 23) and an
      increased tolerance to Zn2+ challenge (measured on both days 27 and 50).
      Unidirectional Zn2+ influx, measured at the end of the exposure period, was
      significantly reduced in the Zn2+-exposed fish. There were no changes in hepatic
      or branchial Zn2+, Cu2+ or metallothionein concentrations. We hypothesize that,
      during exposure to sublethal [Zn2+] in hard water, the fish may change the Km for
      a mutual Ca2+/Zn2+ carrier so as to reduce markedly Zn2+ influx without greatly
      altering Ca2+ influx. This reduced Zn2+ influx, rather than metallothionein
      induction, may be the basis of adaptation to elevated concentrations of
      waterborne Zn2+.

PMID- 7525830
TI  - The Na(+)-independent taurine influx in flounder erythrocytes and its association
      with the volume regulatory taurine efflux.
AB  - 95% of the Na(+)-independent influx of taurine in flounder erythrocytes at normal
      osmolality (330 mosmol kg-1) and 0.30 mmol l-1 taurine was mediated by a
      saturable system (Vmax = 0.689 nmol g-1 dry mass min-1; Km = 0.47 mmol l-1). The
      influx was inhibited by taurine analogues, but was not significantly affected by
      reduced osmolality. This saturable influx of taurine was probably mediated by the
      so-called Na(+)-dependent influx system for taurine operating in the 0 Na+: 1
      taurine mode. The remaining 5% of the Na(+)-independent influx was mediated by a
      diffusional pathway (Kd = 0.050 microliter g-1 dry mass min-1), since it did not
      show saturation kinetics, was not inhibited by taurine analogues and did not
      mediate counter-exchange. This non-saturable influx system for taurine was
      strongly, but transiently, stimulated by reduction of osmolality. The time course
      for this stimulatory effect was the same as that for the system that mediates the
      volume regulatory efflux of taurine. The relative inhibitory effect of
      bumetanide, furosemide, DIDS and quinine on the fluxes mediated by these two
      transport systems were also the same. We suggest that these unidirectional fluxes
      of taurine were mediated by only one transport system: a taurine channel. The
      effect of reduction of osmolality on the rate coefficient for efflux of beta
      alanine was equal to the effect on the efflux of taurine, but greater than the
      effect on the efflux of choline. This difference probably reflects structural
      and/or electrical restrictions on the substrates to be transported by the taurine
      channel. The volume regulatory efflux of taurine was inhibited in the presence of
      the anti-calmodulin drug trifluoperazine and, in a Ca(2+)-free medium, added
      EGTA. The 5-lipoxygenase inhibitor nordihydroguaiaretic acid completely blocked
      the volume regulatory efflux of taurine. We suggest that both Ca2+/calmodulin and
      leukotrienes contribute to the control of the transport mediated by the taurine
      channel.

PMID- 7525832
TI  - Somatostatin-related peptides isolated from the eel gut: effects on ion and water
      absorption across the intestine of the seawater eel.
AB  - Four somatostatin-related peptides were isolated from eel guts. Two of them were
      the same as eel SS-25II (eSS-25II) and eel SS-25I (eSS-25I) isolated from
      European eel pancreas. The remaining two peptides were C-terminal
      tetradecapeptides (eSS-14II and eSS-14I) of eSS-25II and eSS-25I, respectively.
      These four peptides all enhanced the serosa-negative transepithelial potential
      difference and short-circuit current across the seawater eel intestine after
      pretreatment with isobutylmethylxanthine, serotonin (5-HT) and methacholine, an
      agonist of acetylcholine (ACh). Among these peptides, eSS-25II was the most
      potent enhancer, followed by eSS-25I and eSS-14II. Since the large peptide (eSS
      25II) acts at a lower concentration than the small somatostatin (eSS-14II), the
      11 N-terminal amino acid residues seem to potentiate somatostatin action in the
      eel intestine. In contrast, eSS-14II was more potent than mammalian SS-14,
      indicating that the three amino acid residues (Tyr18, Gly21, Pro22) in the C
      terminal portion also contribute to the potency of somatostatin. Endogenous
      somatostatin (eSS-25II) activated net Na+, Cl- and water fluxes across the
      seawater eel intestine. This stimulatory action was not inhibited by tetrodotoxin
      or yohimbine, an adrenergic antagonist, indicating that eSS-25II does not act
      through neuronal firing or through catecholamine release. Thus, eel somatostatins
      may act directly on the enterocytes, but on a distinct receptor from that for
      adrenaline, to antagonize the inhibition of NaCl and water absorption by 5-HT and
      ACh in the seawater eel intestine.

PMID- 7525828
TI  - Expression of 17 beta-hydroxysteroid dehydrogenase in human granulosa cells:
      correlation with follicular size, cytochrome P450 aromatase activity and
      oestradiol production.
AB  - The aim of this study was to examine the expression and regulation of type 1 17
      beta-hydroxysteroid dehydrogenase (type 1 17-HSD) enzyme protein and mRNA, and 17
      HSD activity in human granulosa cells. The cells were obtained from patients
      taking part in an in vitro fertilization programme. The cells from each patient
      were divided into two groups: cells obtained from preovulatory follicles (LGC =
      granulosa cells from large follicles > or = 18 mm in diameter), and cells from
      other visible follicles (SGC = granulosa cells from small follicles, less than 15
      mm in diameter). The identity of 17-HSD enzyme protein expressed in human
      granulosa cells with placental cytosolic 17-HSD (type 1 17-HSD) was assessed by
      immunoblot analysis using polyclonal antibodies, and the enzyme was
      immunolocalized in the cytoplasm of granulosa cells. Type 1 17-HSD protein
      concentration, 17-HSD and cytochrome P450 aromatase (P450arom) activities and
      oestradiol (OE2) production in cells from LGC were significantly lower than the
      corresponding values obtained in SGC in the same patient (paired t-test). The
      type 1 17-HSD protein concentration, 17-HSD activity and P450arom activity were
      140 +/- 16% (mean +/- S.E.M.), 121 +/- 22% and 113 +/- 26% higher in cells from
      SGC, which was also reflected in a 70 +/- 12% higher OE2 production in these
      cells. In freshly isolated cells from LGC or SGC, a high correlation between 17
      HSD and P450arom activities was observed (r = 0.93, P < 0.001). In long-term
      cultured cells, type 1 17-HSD was stably expressed at least until day 9, while
      P450arom expression decreased. In addition, treatments with gonadotrophins did
      not affect type 1 17-HSD protein concentration and 17-HSD activity. In contrast
      to this, both P450arom activity and OE2 production were significantly increased
      (P < 0.05). The data, therefore, suggest that type 1 17-HSD and P450arom are
      expressed in parallel during the latest stages of follicular maturation but, in
      cultured granulosa-luteal cells, the enzymes are regulated by distinct
      mechanisms.

PMID- 7525834
TI  - In vivo effects of monoclonal antibodies that functionally inhibit complement
      regulatory proteins in rats.
AB  - The present work was designed to evaluate the effects of functional suppression
      of complement regulatory proteins in vivo. Male Wistar rats were anesthetized
      with Nembutal and were intravenously injected with 1 mg/kg of F(ab')2 or Fab
      fraction of either monoclonal antibody 5I2, which inhibits the function of rat
      counterpart of mouse Crry/p65, or monoclonal antibody 6D1, which inhibits the rat
      counterpart of CD59. Mean arterial pressure was continuously measured for 30 min.
      When 5I2 was injected, there was a biphasic change of mean arterial pressure,
      namely, the rapid increase immediately after the injection (approximately 2 min,
      phase 1) and the subsequent fall and slow recovery (approximately 4-30 min, phase
      2). These effects were completely abrogated by pretreatment of rats with cobra
      venom factor. Pretreatment with carboxypeptidase inhibitor, which inhibits
      inactivation of anaphylatoxins C3a and C5a, induced enhanced reduction of blood
      pressure. Circulating leukocytes and platelets were rapidly decreased 5 min after
      antibody injection and became normal by 2 h. Hematocrit and erythrocyte count
      were continuously increased up to 2 h after injection, suggesting that there was
      hemoconcentration due to increased vascular permeability. Immunofluorescence
      study revealed binding of antibody fragments and rat C3 along the capillaries of
      lung, heart, and liver 5 min after injection. In contrast to 5I2, F(ab')2
      fraction of 6D1, though localized to the same areas and in similar amounts, had
      no significant effect on the parameters measured. These data suggest that the rat
      counterpart of mouse Crry/p65 plays a vital role in vivo by preventing the
      activation of autologous complement on vascular endothelium.

PMID- 7525836
TI  - Generation of polarized antigen-specific CD8 effector populations: reciprocal
      action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine
      profiles.
AB  - We have generated primary effector populations from naive CD8 T cells in response
      to antigen and determined their patterns of cytokine secretion upon
      restimulation. The effect of exogenous factors on the effector generation was
      examined and compared with responses of antigen-specific CD4 effectors generated
      under comparable conditions. CD8 cells from bm1 mice were stimulated with C57BL/6
      (B6) antigen presenting cells (APCs) bearing allogeneic class I and CD8 cells
      from female severe combined immunodeficiency (SCID) B6 mice, transgenic for a T
      cell receptor alpha/beta (TCR-alpha/beta) that recognizes H-Y on Db, were
      stimulated with APCs from male mice. In parallel, CD4 cells from bm12 mice were
      stimulated with alloantigen and CD4 cells from V beta 3/V alpha 11 TCR
      transgenics were stimulated with a peptide of pigeon cytochrome c on IEk. T cells
      from both transgenic mice were of naive phenotype whereas normal mice contained
      10-20% memory cells. Effector CD8 populations generated were L-selectin low,
      CD45RB high, and CD44 high. Naive CD8 cells from SCID anti-H-Y mice made little
      or no cytokine immediately upon stimulation in contrast to naive CD4 which
      produced large amounts of interleukin 2 (IL-2). Both populations, however,
      generated primary effectors over 4-5 d that made substantial quantities of many
      cytokines upon restimulation. Both CD8 and CD4 effectors produced similar
      patterns of cytokines with alloantigen or specific antigen. Cytokines present
      during naive CD8 stimulation influenced the cytokine secretion profile of the
      effectors, as previously shown for CD4 cells, although secretion by CD8 effectors
      was generally lower than that of CD4 effectors. CD8 cells cultured with IL-2
      alone made predominantly interferon gamma (IFN-gamma) and no IL-4 or IL-5,
      similar to CD4 cells. Priming with IFN-gamma increased IFN-gamma secretion from
      CD4 effectors, but had little if any effect on CD8 cells. In contrast, priming
      with IL-12 generated CD8 effectors, as well as CD4 effectors, producing elevated
      quantities of IFN-gamma, with similar levels from both the CD4 and CD8
      populations. The presence of IL-4 during effector cell generation promoted
      synthesis of IL-4 and IL-5 from both CD8 and CD4 cells while downregulating IFN
      gamma secretion. CD8 cells made only small amounts of IL-4, more than 100-fold
      less than CD4 cells, whereas significant levels of IL-5 were induced, only 3-10
      fold lower than from CD4.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525835
TI  - CD2 is involved in maintenance and reversal of human alloantigen-specific clonal
      anergy.
AB  - Induction and maintenance of a state of T cell unresponsiveness to specific
      alloantigen would have significant implications for human organ transplantation.
      Using human histocompatibility leukocyte antigen DR7-specific helper T cell
      clones, we demonstrate that blockade of the B7 family of costimulatory molecules
      is sufficient to induce alloantigen-specific T cell clonal anergy. Anergized
      cells do not respond to alloantigen and a variety of costimulatory molecules,
      including B7-1, B7-2, intercellular adhesion molecule-1 (ICAM-1), and lymphocyte
      function-associated molecule (LFA)-3. However, after culture in exogenous
      interleukin (IL)-2 for at least 7 d, anergized cells can respond to alloantigen
      in the presence of LFA-3. LFA-3 costimulation subsequently restores
      responsiveness to alloantigen in the presence of previously insufficient
      costimulatory signals. Expression of CD2R epitope is downregulated on anergic
      cells and is restored after 7 d of IL-2 culture. The loss of the CD2R is
      temporally associated with the inability of anergized cells to respond to LFA-3.
      These results suggest that in addition to blockade of B7 family members,
      inhibition of CD2 and, potentially, other costimulatory pathways that might
      reverse anergy will be necessary to maintain prolonged alloantigen-specific
      tolerance.

PMID- 7525838
TI  - Neutrophils roll on adherent neutrophils bound to cytokine-induced endothelial
      cells via L-selectin on the rolling cells.
AB  - Specific arrest of neutrophils in venules is central to their rapid accumulation
      during local inflammatory responses. Initial neutrophil rolling on endothelium is
      mediated by leukocyte L-selectin and the inducible vascular adhesion proteins P-
      and E-selectin. This rolling is a prerequisite for endothelial-dependent
      neutrophil arrest. Here we describe rolling of neutrophils on the surface of
      previously arrested neutrophils and demonstrate that this interaction involves L
      selectin exclusively on rolling cells. The adherent neutrophil support of L
      selectin-dependent neutrophil rolling in vivo can promote continuous and
      augmented leukocyte recruitment at sites of previous neutrophil accumulation.

PMID- 7525837
TI  - Analysis of the structure of empty and peptide-loaded major histocompatibility
      complex molecules at the cell surface.
AB  - We compared the conformation of empty and peptide-loaded class I major
      histocompatibility complex (MHC) molecules at the cell surface. Molecular
      conformations were analyzed by fluorescence resonance energy transfer (FRET)
      between fluorescent-labeled Fab fragments bound to the alpha 2 domain of the MHC
      heavy chain and fluorescent-labeled Fab fragments bound to beta 2-microglobulin.
      No FRET was found between Fab fragments bound to empty H-2Kb, but FRET was
      detected when empty H-2Kb molecules were loaded with peptide. The magnitude of
      FRET depended on the sequence of the peptide used. The results imply that empty H
      2Kb molecules are in a relatively extended conformation, and that this
      conformation becomes more compact when peptide is bound. These changes, which are
      reflected in peptide-dependent binding of monoclonal antibodies, affect the
      surfaces of MHC molecules available for contact with T cell receptors and hence
      may influence T cell-receptor recognition of MHC molecules.

PMID- 7525840
TI  - B70/B7-2 is identical to CD86 and is the major functional ligand for CD28
      expressed on human dendritic cells.
AB  - Dendritic cells comprise a system of highly efficient antigen-presenting cells
      involved in the initiation of T cell responses. Herein, we investigated the role
      of the CD28 pathway during alloreactive T cell proliferation induced by dendritic
      Langerhans cells (D-Lc) generated by culturing human cord blood CD34+ progenitor
      cells with granulocyte/macrophage colony-stimulating factor and tumor necrosis
      factor alpha. In addition to expressing CD80 (B7/BB1), a subset of D-Lc expressed
      B70/B7-2. Binding of the CTLA4-Ig fusion protein was completely inhibited by a
      combination of monoclonal antibodies (mAbs) against CD80 and B70/B7-2, indicating
      the absence of expression of a third ligand for CD28/CTLA-4. It is interesting to
      note that mAbs against CD86 completely prevented the binding of CTLA4-Ig in the
      presence of mAbs against CD80 and bound to a B70/B7-2-transfected fibroblast cell
      line, demonstrating that the B70/B7-2 antigen is identical to CD86. CD28
      triggering was essential during D-Lc-induced alloreaction as it was inhibited by
      mAbs against CD28 (9 out of 11 tested). However, none of six anti-CD80 mAbs
      demonstrated any activity on the D-Lc-induced alloreaction, though some were
      previously described as inhibitory in assays using CD80-transfected cell lines.
      In contrast, a mAb against CD86 (IT-2) was found to suppress the D-Lc-dependent
      alloreaction by 70%. This inhibitory effect was enhanced to > or = 90% when a
      combination of anti-CD80 and anti-CD86 mAbs was used. The present results
      demonstrate that D-Lc express, in addition to CD80, the other ligand for CTLA-4,
      CD86 (B70/B7-2), which plays a primordial role during D-Lc-induced alloreaction.

PMID- 7525841
TI  - The tissue distribution of the B7-2 costimulator in mice: abundant expression on
      dendritic cells in situ and during maturation in vitro.
AB  - B7-2 is a recently discovered, second ligand for the CTLA-4/CD28, T cell
      signaling system. Using the GL-1 rat monoclonal antibody (mAb), we monitored
      expression of B7-2 on mouse leukocytes with an emphasis on dendritic cells. By
      cytofluorography, little or no B7-2 was detected on most cell types isolated from
      spleen, thymus, peritoneal cavity, skin, marrow, and blood. However, expression
      of B7-2 could be upregulated in culture. In the case of epidermal and spleen
      dendritic cells, which become highly immunostimulatory for T cells during a short
      period of culture, the upregulation of B7-2 was dramatic and did not require
      added stimuli. Lipopolysaccharide did not upregulate B7-2 levels on dendritic
      cells, in contrast to macrophages and B cells. By indirect immunolabeling, the
      level of staining with GL-1 mAb exceeded that seen with rat mAbs to several other
      surface molecules including intercellular adhesion molecule 1, B7-1, CD44, and
      CD45, as well as new hamster mAbs to CD40, CD48, and B7-1/CD80. Of these
      accessory molecules, B7-2 was a major species that increased in culture, implying
      a key role for B7-2 in the functional maturation of dendritic cells. B7-2 was the
      main (> 90%) CTLA-4 ligand on mouse dendritic cells. When we applied GL-1 to
      tissue sections of a dozen different organs, clear-cut staining with B7-2 antigen
      was found in many. B7-2 staining was noted on liver Kupffer cells, interstitial
      cells of heart and lung, and profiles in the submucosa of the esophagus. B7-2
      staining was minimal in the kidney and in the nonlymphoid regions of the gut, and
      was not observed at all in the brain. In the tongue, only rare dendritic cells in
      the oral epithelium were B7-2+, but reactive cells were scattered about the
      interstitial spaces of the muscle. In all lymphoid tissues, Gl-1 strongly stained
      certain distinct regions that are occupied by dendritic cells and by macrophages.
      For dendritic cells, these include the thymic medulla, splenic periarterial
      sheaths, and lymph node deep cortex; for macrophages, the B7-2-rich regions
      included the splenic marginal zone and lymph node subcapsular cortex. Splenic B7
      2+ cells were accessible to labeling with GL-1 mAb given intravenously. Dendritic
      cell stimulation of T cells (DNA synthesis) during the mixed leukocyte reaction
      was significantly (35-65%) blocked by GL-1.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525842
TI  - Interaction between human CD2 and CD58 involves the major beta sheet surface of
      each of their respective adhesion domains.
AB  - The CD58 binding site on human CD2 was recently shown by nuclear magnetic
      resonance structural data in conjunction with site-directed mutagenesis to be a
      highly charged surface area covering approximately 770A2 on the major AGFCC'C"
      face of the CD2 immunoglobulin-like (Ig-like) NH2-terminal domain. Here we have
      identified the other binding surface of the CD2-CD58 adhesion pair by mutating
      charged residues shared among CD2 ligands (human CD58, sheep CD58, and human
      CD48) that are predicted to be solvent exposed on a molecular model of the Ig
      like adhesion domain of human CD58. This site includes beta strand residues along
      the C strand (E25, K29, and K30), in the middle of the C' strand (E37) and in the
      G strand (K87). In addition, several residues on the CC' loop (K32, D33, and K34)
      form this site. Thus, the interaction between CD2 and CD58 involves the major
      beta sheet surface of each adhesion domain. Possible docking orientations for the
      CD2-CD58 molecular complex are offered. Strict conservation of human and sheep
      CD58 residues within the involved C and C' strands and CC' loop suggests that
      this region is particularly important for stable formation of the CD2-CD58
      complex. The analysis of this complex offers molecular insight into the nature of
      a receptor-ligand pair involving two Ig family members.

PMID- 7525843
TI  - Thymic selection and adaptability of cytotoxic T lymphocyte responses in
      transgenic mice expressing a viral protein in the thymus.
AB  - Upon primary challenge with lymphocytic choriomeningitis virus (LCMV), H-2d
      (BALB/cByJ) mice mount a cytotoxic T lymphocyte (CTL) response to a single
      immunodominant domain of the viral nucleoprotein (NP) but no detectable response
      to the viral glycoprotein (GP). To manipulate this CTL response, the viral NP
      gene was expressed in the thymus and peripheral T lymphocytes using the murine
      Thy1.2 promoter. As a result, such Thy1.2-NP (H-2d) transgenic (tg) mice deleted
      their high-affinity anti-LCMV-NP CTL, but generated equal numbers of lower
      affinity NP CTL. Further, they made an alternative anti-LCMV-GP CTL response that
      is not normally found in non-tg mice indicating a hierarchial control of the CTL
      response. Unlike the H-2d mice, H-2b (C57Bl/6J) mice normally mount a CTL
      response to both LCMV-GP and -NP. When the LCMV-NP was expressed using the Thy1.2
      promoter in these H-2b mice, the LCMV-NP-specific CTL response was completely
      aborted and no CTL to new, alternative viral epitopes were generated. Dilutions
      of H-2b or H-2d NP peptides indicated that 3-4 logs less H-2b NP peptide was
      required to sensitize syngeneic target cells for CTL-specific lysis, suggesting
      that the differing affinities of H-2b and H-2d major histocompatibility complex
      molecules for their peptides likely account for the total removal of NP CTL in
      the H-2b mice but only partial removal in H-2d mice made to express thymic NP.
      Thymic grafting experiments done with thymi from newborn Thy1.2-NP tg mice show
      that selection processes studied in this model are of central (thymic) origin and
      are not caused by Thy1.2-positive LCMV-NP-expressing T lymphocytes in the
      periphery.

PMID- 7525839
TI  - A quantitative analysis of antigen-presenting cell function: activated B cells
      stimulate naive CD4 T cells but are inferior to dendritic cells in providing
      costimulation.
AB  - Ligation of CD28 on CD4 Th1 clones and freshly isolated mixtures of naive and
      memory CD4 T cells triggered their T cell receptors (TCR) is sufficient to induce
      the costimulatory signals necessary for interleukin 2 (IL-2) production by these
      cells. CTLA-4-reactive ligands expressed on antigen-presenting cells (APC) are
      critical in providing costimulatory signals to these T cell populations. We
      demonstrate that these activation characteristics apply equally to purified naive
      CD4 T cells. Because B cell blasts express CTLA-4-reactive ligands and high
      levels of adhesion and major histocompatibility complex class II molecules, they
      would be expected to engage both the TCR and CD28 and consequently stimulate IL-2
      production by naive CD4 T cells. Using purified populations of cells in limiting
      dilution cultures, we have carried out a quantitative analysis of the interaction
      between naive CD4 T cells and either activated B or dendritic cells. We
      demonstrate that B cell blasts stimulate a high frequency of naive CD4 T cells.
      Slight differences in TCR signaling efficiency between the two APC types were
      observed. Even at optimal peptide concentrations, however, the amount of IL-2
      made by individual T cells was fourfold lower in response to B cell blasts than
      to dendritic cells. This relative deficiency of activated B cells was due to
      their inability to optimally costimulate naive CD4 T cells.

PMID- 7525844
TI  - Apolipoprotein E (ApoE), a novel heparin-binding protein inhibits the development
      of Kaposi's sarcoma-like lesions in BALB/c nu/nu mice.
AB  - Recombinant apolipoprotein E-3 (ApoE-3), expressed in Escherichia coli, was
      purified and used in an in vitro and an in vivo model system for acquired
      immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS). This protein
      blocked cell proliferation and chemotaxis of AIDS-KS cells in response to
      activated lymphocyte conditioned medium (AL-CM) and oncostatin M (OSM). ApoE-3
      also inhibited the formation of neoangiogenic lesions induced in BALB/c nu/nu
      mice by AIDS-KS cells. These findings represent a novel and potentially less
      toxic therapeutic approach for the treatment of AIDS-KS.

PMID- 7525845
TI  - Cytokine-induced immune deviation as a therapy for inflammatory autoimmune
      disease.
AB  - The properties and outcome of an immune response are best predicted by the
      lymphokine phenotype of the responding T cells. Cytokines produced by CD4+ T
      helper type 1 (Th1) T cells mediate delayed type hypersensitivity (DTH) and
      inflammatory responses, whereas cytokines produced by Th2 T cells mediate helper
      T cell functions for antibody production. To determine whether induction of Th2
      like cells would modulate an inflammatory response, interleukin 4 (IL-4) was
      administered to animals with experimental allergic encephalomyelitis (EAE), a
      prototypic autoimmune disease produced by Th1-like T cells specific for myelin
      basic protein (MBP). IL-4 treatment resulted in amelioration of clinical disease,
      the induction of MBP-specific Th2 cells, diminished demyelination, and inhibition
      of the synthesis of inflammatory cytokines in the central nervous system (CNS).
      Modulation of an immune response from one dominated by excessive activity of Th1
      like T cells to one dominated by the protective cytokines produced by Th2-like T
      cells may have applicability to the therapy of certain human autoimmune diseases.

PMID- 7525846
TI  - T cell recognition of an HLA-A2-restricted epitope derived from a cleaved signal
      sequence.
AB  - An alternative pathway for class I-restricted antigen presentation has been
      suggested on the basis of peptides bound to HLA-A2 molecules in cells lacking the
      transporter for antigen presentation (TAP). Most of these peptides were derived
      from signal sequences for translocation into the endoplasmic reticulum (ER).
      However, it is not known whether these peptides can be presented to T cells. The
      hydrophobic nature of an HLA-A2-restricted T cell epitope (M1 58-66) was
      exploited to test whether it could be presented to T cells when derived from a
      signal sequence. Replacing the signal sequence of the influenza virus
      hemagglutinin molecule H3 with an artificial sequence containing that HLA-A2
      restricted T cell epitope resulted in efficient translocation of H3 molecules
      into the ER and transport to the cell surface. This signal sequence-derived
      epitope was presented to HLA-A2-restricted T cells. Involvement of cytosolic
      processing for this presentation is very unlikely, because (a) presentation
      occurred in cells lacking TAP; (b) expression of H3 molecules with the artificial
      signal sequence did not produce a detectable cytosolic form of H3; and (c)
      presentation of the same epitope expressed in cytosolic forms of antigen required
      TAP. Thus, a peptide derived from a signal sequence cleaved in the ER can provide
      an epitope for HLA-A2-restricted T cell recognition.

PMID- 7525847
TI  - IL-5 receptor-mediated tyrosine phosphorylation of SH2/SH3-containing proteins
      and activation of Bruton's tyrosine and Janus 2 kinases.
AB  - Interleukin 5 (IL-5) induces proliferation and differentiation of B cells and
      eosinophils by interacting with its receptor (IL-5R) which consists of two
      distinct polypeptide chains, alpha and beta (beta c). Although both IL-5R alpha
      and beta c lack a kinase catalytic domain, IL-5 is capable of inducing tyrosine
      phosphorylation of cellular proteins. We investigated the role of IL-5R alpha in
      tyrosine phosphorylation of molecules involved in IL-5 signal transduction, using
      an IL-5-dependent early B cell line, Y16 and transfectants expressing intact or
      mutant IL-5R alpha together with intact beta c. The results revealed that the
      transfectants expressing truncated IL-5R alpha, which entirely lacks a
      cytoplasmic domain, together with beta c, showed neither protein-tyrosine
      phosphorylation nor proliferation in response to IL-5. This confirms that IL-5R
      alpha plays a critical role in protein-tyrosine phosphorylation which triggers
      cell growth. IL-5 stimulation results in rapid tyrosine phosphorylation of beta c
      and proteins containing Src homology 2 (SH2) and/or SH3 domains such as
      phosphatidyl-inositol-3 kinase, Shc, Vav, and HS1, suggesting their involvement
      in IL-5-mediated signal transduction. IL-5 stimulation significantly enhanced
      activities of Janus 2 and B cell-specific Bruton's tyrosine kinases (JAK2 and
      Btk) and increased the tyrosine phosphorylation of JAK2 kinase. These results and
      recent data on signaling of growth factors taken together, multiple biochemical
      pathways driven by tyrosine kinases such as JAK2 and Btk are involved in IL-5
      signal transduction.

PMID- 7525849
TI  - Sulfation-dependent recognition of high endothelial venules (HEV)-ligands by L
      selectin and MECA 79, and adhesion-blocking monoclonal antibody.
AB  - L-selectin is a lectin-like receptor that mediates the attachment of lymphocytes
      to high endothelial venules (HEV) of lymph nodes during the process of lymphocyte
      recirculation. Two sulfated, mucin-like glycoproteins known as Sgp50/GlyCAM-1 and
      Sgp90/CD34 have previously been identified as HEV-associated ligands for L
      selectin. These proteins were originally detected with an L-selectin/Ig chimera
      called LEC-IgG. GlyCAM-1 and CD34 are also recognized by an antiperipheral node
      addressin (PNAd) mAb called MECA 79, which blocks L-selectin-dependent adhesion
      and selectively stains lymph node HEV. The present study compares the
      requirements for the binding of MECA 79 and LEC-IgG to HEV-ligands. Whereas
      desialylation of GlyCAM-1 and CD34 drastically reduced binding to LEC-IgG, this
      treatment enhanced the binding of GlyCAM-1 to MECA 79. In contrast, the binding
      of both MECA 79 and LEC-IgG to GlyCAM-1 and CD34 was greatly decreased when the
      sulfation of these ligands was reduced with chlorate, a metabolic inhibitor of
      sulfation. Because MECA 79 stains HEV-like vessels at various sites of
      inflammation, recognition by L-selectin of ligands outside of secondary lymphoid
      organs may depend on sulfation. In addition to their reactivity with GlyCAM-1 and
      CD34, both MECA 79 and LEC-IgG recognize an independent molecule of approximately
      200 kD in a sulfate-dependent manner. Thus, this molecule, which we designate
      Sgp200, is an additional ligand for L-selectin.

PMID- 7525848
TI  - Costimulation by purified intercellular adhesion molecule 1 and lymphocyte
      function-associated antigen 3 induces distinct proliferation, cytokine and cell
      surface antigen profiles in human "naive" and "memory" CD4+ T cells.
AB  - Activation of resting human CD4+ "naive" (CD45RA+CD45RO-) and "memory" (CD45RA
      CD45RO+) T cells requires costimulatory signals in addition to engagement of the
      T cell receptor/CD3 complex (TCR/CD3). The adhesion pathways mediated by
      lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 (LFA
      1/ICAM-1) and CD2/LFA-3 are capable of providing such costimulatory signals. Our
      work shows that these costimulatory adhesion pathways are critically involved in
      regulation of T cell differentiation/maturation. Evidence for subset-specific
      costimulatory requirements is demonstrated by the finding that only memory CD4+ T
      cells were costimulated by LFA-3, whereas both naive and memory CD4+ T cells were
      costimulated by ICAM-1. In addition, these costimulatory adhesion pathways
      regulated reciprocal cytokine secretion patterns for interleukin 5 (IL-5) and
      granulocyte/macrophage colony-stimulating factor (GM-CSF). Repeated costimulation
      of CD4+ memory T cells with LFA-3 led to secretion of high levels of IL-5, while
      repeated costimulation with ICAM-1 induced high levels of secreted GM-CSF.
      Significant interferon gamma (IFN-gamma) production was observed with either of
      the costimulatory ligands. Extensive cell surface analysis of these in vitro
      cultures of peripheral blood derived memory CD4+ T cells, with monoclonal
      antibodies obtained from the 5th Leucocyte Typing Workshop, revealed differential
      expression of a singular antigen, CD60. This antigen was preferentially expressed
      on LFA-3-costimulated cells suggesting a positive correlation between CD60
      expression and a T helper type 2-like cytokine profile. In conclusion, this
      report demonstrates a new functional role for costimulatory adhesion molecules in
      regulating differential cytokine secretion in human memory CD4+ T cells.

PMID- 7525850
TI  - Reversal of experimental autoimmune encephalomyelitis by a soluble peptide
      variant of a myelin basic protein epitope: T cell receptor antagonism and
      reduction of interferon gamma and tumor necrosis factor alpha production.
AB  - An immunodominant epitope of myelin basic protein (MBP), VHFFKNIVTPRTP (p87-99),
      is a major target of T cells in lesions of multiple sclerosis (MS) and in
      experimental allergic encephalomyelitis (EAE). T cells found in EAE lesions bear
      the same amino acids in the third complementary determining region of the T cell
      receptor (TCR) as those found in MS lesions. We analyzed the trimolecular
      interactions between MBP p87-99, class II major histocompatibility complex (MHC),
      and TCR, and designed soluble inhibitors for therapy. F, N, I, and V at positions
      90, 92, 93, and 94 interact with MHC, whereas K, T, and P at positions 91, 95,
      and 96 interact with TCR. The peptides, p87-99[95T > A] and p87-99[96P > A] could
      compete more effectively with p87-99 for binding to MHC and could antagonize the
      in vitro response to T cells to p87-99 more effectively than p87-99[91K > A].
      However, only p87-99[91K > A] prevented and reversed EAE, indicating that the
      extent of MHC or TCR competition does not predict success in treating EAE. To
      elucidate the mechanism of inhibition of EAE, draining lymph node cells from rats
      immunized with the native peptide alone or together with each of the three TCR
      antagonists were challenged in vitro with p87-99. Administration of p87-99[91K >
      A], but not p87-99 [95T > A] or p87-99[96P > A], reduced the production of tumor
      necrosis factor (TNF)- alpha and interferon (IFN) gamma. IFN-gamma and TNF-alpha
      are two cytokines that are critical in the pathogenesis of EAE and MS.

PMID- 7525855
TI  - Effects of 5-fluorouracil on macromolecular synthesis during secondary palate
      development in quail.
AB  - A study was undertaken to examine the growth of normal and 5-fluorouracil-treated
      quail secondary palate during embryogenesis. The rates of DNA, RNA, and protein
      synthesis were measured in the developing quail palate by liquid scintillation
      counting of radiolabelled thymidine, uridine, or leucine. In addition, shelf
      volume was determined morphometrically. The results showed that in control
      palates the shelf volume increased rapidly between days 5 and 7 of incubation.
      Drug treatment on day 4 did not alter the shelf volume until day 9 of incubation,
      at which time the treated shelves were smaller than controls. In control palates,
      the rate of DNA synthesis decreased steadily between days 5 and 9 of incubation.
      A burst in RNA synthesis on day  7 of incubation was followed by an increase in
      protein synthesis. Administration of FU seems to exert its effect via disturbing
      the synthesis of RNA and protein, instead of disruption of DNA synthesis, to
      ultimately affect the shelf area, and thus palate morphogenesis in quail.
      Comparison of avian and mammalian data indicated that differences in their palate
      morphogenesis are also reflected in the different temporal patterns of various
      macromolecular synthesis.

PMID- 7525854
TI  - Entry of naive CD4 T cells into peripheral lymph nodes requires L-selectin.
AB  - Binding of L-selectin expressed on lymphocytes to carbohydrate ligand(s) on lymph
      node high endothelial venules is thought to initiate lymphocyte extravasation
      from blood to lymph during recirculation and localization to sites of antigen
      (Ag) exposure. Previous studies have shown that treatment of lymphocytes with
      antibody to L-selectin (MEL-14) ablates trafficking to peripheral lymph nodes
      (PLN). In mice, naive but not memory CD4 cells express L-selectin. To examine the
      role of L-selectin in helper T cell migration, we studied the effects of in vivo
      administration of MEL-14 on CD4 cell responses. Systemic exposure of mice to MEL
      14 depleted CD4 cells expressing a naive phenotype (CD45RBhi, CD44lo) from PLN
      but not from spleen. The majority of residual lymph node CD4 cells exhibited the
      reciprocal, memory phenotype (CD45RBlo, CD44hi). MEL-14 treatment prevented
      priming of naive CD4 cells for proliferation and cytokine production (IL-2 and IL
      4) to keyhole limpet hemocyanin in PLN draining the site of Ag injection, but not
      in the spleen. The results suggest that naive cells were not depleted, but rather
      diverted to other sites where priming occurred. The data demonstrate that L
      selectin mediates extravasation of naive CD4 cells into PLN and that its function
      cannot be replaced by other homing receptors.

PMID- 7525856
TI  - Amplification of cDNA via RT-PCR using RNA extracted from postmortem tissues.
AB  - Analysis of cDNA derived from messenger RNA is of advantage over using genomic
      DNA in genetic analysis of large genes, especially those with lengthy intron
      sequences. However, because of its instability and rapid degradation, RNA
      extraction from postmortem tissues has not been attempted. Here, we report the
      successful extraction of intact mRNA from various postmortem tissues from
      accidental and sudden death cases. Subsequently with reverse transcriptase
      polymerase chain reaction (RT-PCR), we were able to amplify cDNA fragments of
      different lengths up to 0.9 kb. The described method therefore provides a useful
      tool in genetic analysis of postmortem tissues.

PMID- 7525852
TI  - Reverse transcriptase-dependent and -independent phases of infection with mouse
      mammary tumor virus: implications for superantigen function.
AB  - Mouse mammary tumor virus (MMTV) encodes a superantigen (SAg) that promotes
      stable infection and virus transmission. Upon subcutaneous MMTV injection,
      infected B cells present SAg to SAg-reactive T cells leading to a strong local
      immune response in the draining lymph node (LN) that peaks after 6 d. We have
      used the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (AZT) to
      dissect in more detail the mechanism of SAg-dependent enhancement of MMTV
      infection in this system. Our data show that no detectable B or T cell response
      to SAg occurs in AZT pretreated mice. However, if AZT treatment is delayed 1-2 d
      after MMTV injection, a normal SAg-dependent local immune response is observed on
      day 6. Quantitation of viral DNA in draining LN of these infected mice indicates
      that a 4,000-fold increase in the absolute numbers of infected cells occurs
      between days 2 and 6 despite the presence of AZT. Furthermore MMTV DNA was found
      preferentially in surface IgG+ B cells of infected mice and was not detectable in
      SAg-reactive T cells. Collectively our data suggest that MMTV infection occurs
      preferentially in B cells without SAg involvement and is completed 1-2 d after
      virus challenge. Subsequent amplification of MMTV infection between days 2 and 6
      requires SAg expression and occurs in the absence of any further requirement for
      reverse transcription. We therefore conclude that clonal expansion of infected B
      cells via cognate interaction with SAg-reactive T cells is the predominant
      mechanism for increasing the level of MMTV infection. Since infected B cells
      display a memory (surface IgG+) phenotype, both clonal expansion and possibly
      longevity of the virus carrier cells may contribute to stable MMTV infection.

PMID- 7525857
TI  - Granulocyte colony stimulating factor.
AB  - Recombinant human granulocyte colony-stimulating factor (rhGCSF) has been
      commercially available for two years; yet unanswered questions need to be
      substantiated by clinical trials. The most extensively studied clinical
      application has been in chemotherapy-induced neutropenia. GCSF accelerates
      neutrophil recovery after bone marrow transplant, mobilizes bone marrow
      progenitor cells into peripheral blood harvesting then transplanted as supportive
      measures in patients undergoing intensive chemotherapy, and accelerates
      neutrophil recovery in patients with acute leukemias. GCSF is generally well
      tolerated with only mild to moderate bone pain. Mild reversible elevation in
      lactate dehydrogenase, alkaline phosphatase, and uric acid has been reported. As
      data are obtained from ongoing trials, GCSF's clinical role will be expanded and
      better defined.

PMID- 7525853
TI  - Evidence for the involvement of interleukin 10 in the differential deactivation
      of murine peritoneal macrophages by prostaglandin E2.
AB  - Among other effects, prostaglandins (PG) of the E series are known to inhibit
      several acute and chronic inflammatory conditions in vivo and proinflammatory
      cytokine production by activated macrophages in culture. The research presented
      here demonstrates that the inhibitory effect of PGE2 on tumor necrosis factor
      alpha (TNF-alpha) and interleukin 6 (IL-6) production by lipopolysaccharide (LPS)
      stimulated murine peritoneal macrophages involves IL-10. In a dose-dependent
      manner, PGE2 inhibits LPS-induced release of TNF-alpha and IL-6, but not of
      lactate or nitric oxide. The decrease in the level of these cytokines is
      inversely proportional to the increase in immunoreactive IL-10. This differential
      inhibitory effect of PGE2 is mimicked by agents that elevate intracellular levels
      of cAMP, but not cGMP. Neutralizing anti IL-10 antibody but not neutralizing
      antibodies against other macrophage secretory products (IL-6, leukemia inhibitory
      factor, and transforming growth factor beta [TGF-beta]), significantly reverse
      the potent inhibitory effect of PGE2. In vivo, the administration of PGE2 before
      LPS challenge significantly reduces circulating TNF-alpha and IL-6 levels. Anti
      IL-10 antibody substantially enhanced the LPS-induced TNF-alpha and IL-6 levels
      in mice that received either LPS alone or LPS plus PGE2. These results suggest
      that the anti-inflammatory effect of PGE2 on mononuclear phagocytes is mediated
      in part by an autocrine feedback mechanism involving IL-10.

PMID- 7525858
TI  - Probing for answers. Use of DNA probes in infectious diseases.
AB  - Diagnostic molecular biology is at the forefront in the diagnosis of infectious
      diseases. Through the use of deoxyribonucleic acid (DNA) probes in conjunction
      with other molecular techniques such as polymerase chain reaction (PCR),
      physicians will be able to more rapidly and accurately diagnose causative agents
      in a variety of infectious diseases. This article will focus on the molecular
      basis of these techniques, how they may aid the physician in patient diagnosis,
      and the shortcomings of this new and exciting technology.

PMID- 7525851
TI  - Further characterization of the thrombasthenia-related idiotype OG. Antiidiotype
      defines a novel epitope(s) shared by fibrinogen B beta chain, vitronectin, and
      von Willebrand factor and required for binding to beta 3.
AB  - A patient (OG) with Glanzmann thrombasthenia became refractory to platelet
      transfusion after the production of an immunoglobulin G (IgG) isoantibody (Ab1)
      specific for the integrin subunit beta 3. To determine the frequency at which the
      OG idiotype is found in the general population and in immune-mediated disease
      states, we developed a rabbit polyclonal antibody (Ab2) specific for affinity
      purified OG anti-beta 3 Fab. The binding of Ab2 to Ab1 is inhibited by purified
      alpha IIb beta 3. Ab2 als binds to IgG specific for alpha IIb beta 3 obtained
      from one nonrelated Glanzmann thrombasthenia patient ES who has developed
      isoantibodies of similar specificity. On the other hand, Ab2 does not recognize
      alpha IIb beta 3-specific antibodies produced by two Glanzmann thrombasthenia
      patients, AF and LUC, who have developed isoantibodies with specificities
      distinct from that of the OG isoantibody. Moreover, Ab2 does not recognize alpha
      IIb beta 3-specific antibodies developed by three representative patients with
      (autoimmune) thrombocytopenic purpura or six representative patients with
      alloimmune thrombocytopenias, nor does it bind to IgG from any of 13 nonimmunized
      individuals. We have found that Ab2 also binds to selected protein ligands of
      alpha IIb beta 3 namely, fibrinogen, vitronectin, and von Willebrand factor, but
      not to other protein ligands or control proteins, such a fibronectin, type I
      collagen, and albumin. The epitope(s) recognized by Ab2 on each adhesive protein
      are either very similar or identical since each protein can inhibit the binding
      of Ab2 to any of the other proteins. The epitope on fibrinogen recognized by Ab2
      resides in the B beta chain, and is likely contained within the first 42 amino
      acids from the NH2 terminus. Since OG IgG inhibits fibrinogen binding to alpha
      IIb beta 3, the specificity of the OG idiotype defines a novel binding motif for
      the integrin alpha IIb beta 3 that is shared by fibrinogen, vitronectin, and von
      Willebrand factor, but distinct from previously described RGD-containing sites on
      the fibrinogen, A alpha chain or the fibrinogen gamma chain COOH-terminal
      decapeptide site. Our findings reported here represent an excellent example of
      molecular mimicry in which an antigen-selected, IgG inhibitor of alpha IIb beta 3
      function shares a novel recognition sequence common to three physiologic protein
      ligands of that receptor.

PMID- 7525860
TI  - Dominant glycoprotein epitope of four corners hantavirus is conserved across a
      wide geographical area.
AB  - A newly identified hantavirus, tentatively called Four Corners virus (FCV), was
      found to be the aetiological agent of a 1993 outbreak of hantavirus pulmonary
      syndrome (HPS) in the southwestern United States. Immunodominant epitopes of 43
      and 31 amino acids were identified in the nucleocapsid protein and G1
      glycoprotein, respectively. The G1 genes of different hantaviruses are highly
      divergent, suggesting that geographically diverse FCVs might fail to cross-react
      owing to antigenic drift. We now show that the immunodominant epitope of G1 is
      conserved among 18 FCVs from a broad geographical area, despite extensive
      nucleotide sequence heterogeneity. Antibodies from all 45 HPS patients, separated
      by more than 3000 km were shown to be reactive with the dominant G1 epitope.
      Evidence for limited cross-reactivity between the G1 antigen of a novel
      hantavirus of the cotton rat and that of FCV is presented.

PMID- 7525861
TI  - Identification of Mengo virus T helper cell epitopes.
AB  - To identify Mengo virus-specific T cell epitopes in mice (the natural host for
      the virus), lymph node cells were obtained from BALB/c (H-2d) mice, previously
      immunized with u.v.-inactivated virus, and stimulated in vitro with each of 116
      overlapping peptides (10 to 18 residues long) covering the entire capsid coding
      region (834 amino acids). T cell epitopes were defined on the basis of specific
      peptide-induced lymphocyte proliferation. Where proliferation occurred,
      immunological characterization showed that it was the CD4+ T helper (Th) cell
      subpopulation that was responsible for the Mengo virus-specific response.
      Surprisingly, no Mengo virus Th cell epitopes were found in capsid protein VP1 or
      VP4. Six peptides in VP2 (residues 1 to 15, 99 to 108, 118 to 132, 133 to 147,
      227 to 236 and 247 to 256) identified the positions of separate Th cell epitopes,
      and two overlapping peptides (residues 173 to 182 and 178 to 192) defined an
      additional Th cell immunogenic sequence. Three individual peptides in VP3
      (residues 46 to 58, 136 to 150 and 198 to 212) and two overlapping peptides
      (residues 1 to 15 and 11 to 20) also represent Th cell epitopes. Similar assays
      with C57BL/6 (H-2b) and SJL/J (H-2s) mice showed that the pattern of recognition
      of these peptides was H-2 restricted. Each of the previously identified sites of
      B cell antigenicity in VP2 and VP3 are associated with one Th epitope. Comparison
      of the experimentally determined Th epitopes with potential T cell epitopes
      identified by several predictive strategies revealed only a low correlation
      between authentic and predicted epitopes.

PMID- 7525859
TI  - ATP alters current fluctuations of cystic fibrosis transmembrane conductance
      regulator: evidence for a three-state activation mechanism.
AB  - The cystic fibrosis gene product cystic fibrosis transmembrane conductance
      regulator (CFTR) is a low conductance, cAMP-regulated Cl- channel. Removal of
      cytosolic ATP causes a cessation of cAMP-dependent kinase-phosphorylated CFTR
      channel activity that resumes upon ATP addition. (Anderson, M. P., H. A. Berger,
      D. R. Rich, R. J. Gregory, A. E. Smith, and M. J. Welsh. 1991. Cell. 67:775-784).
      The aim of this study was to quantify possible effects of ATP on CFTR gating. We
      analyzed multichannel records since only 1 of 64 patches contained a single
      channel. ATP increased the channel open probability (Po) as a simple Michaelis
      Menten function of concentration; the effect was half maximal at 24 microM,
      reached a maximum of 0.44, and had a Hill coefficient of 1.13. Since the maximum
      Po was not 1, the simplest description of the effect of ATP on CFTR gating is the
      noncooperative three-state mechanism of del Castillo and Katz (1957. Proceedings
      of the Royal Society of London. B. 146:369-381). We analyzed current fluctuations
      to quantify possible changes in CFTR gating. The power density spectra appeared
      to contain a single Lorentzian in the range of 0.096-31 Hz. Analysis of the
      corner frequency (fc) of this Lorentzian revealed that ATP increased 2 pi fc as a
      Michaelis-Menten function with a Hill coefficient of 1.08, and it provided
      estimates of the ATP dissociation constant (44 tau open (154 ms), and the ATP
      sensitive tau close [(185 ms) (44 microM/[ATP] + 1)]. These results suggest that
      the binding reaction is rapid compared to the opening and closing rates. Assuming
      that there is a single set of closed-to-open transitions, it is possible to
      verify the outcome of fluctuation analysis by comparing fluctuation-derived
      estimates of Po with measures of Po from current records. The two values were
      nearly identical. Thus, noise analysis provides a quantitative description of the
      effect of ATP on CFTR opening. The noncooperative three-state model should serve
      as a basis to understand possible alterations in CFTR gating resulting from
      regulators or point mutations.

PMID- 7525862
TI  - Localization of functional regions of the cucumber mosaic virus RNA replicase
      using monoclonal and polyclonal antibodies.
AB  - Monoclonal antibodies were produced using a purified cucumber mosaic virus (CMV)
      replicase complex, and Escherichia coli-expressed CMV 1a and 2a proteins, as
      immunogens. Five out of eight monoclonal antibodies, which bound to the 1a and 2a
      proteins in immunoblots, inhibited the RNA-dependent RNA polymerase (RdRp)
      activity of the purified replicase complex in vitro. Epitope mapping showed that
      two of the inhibitory antibodies interacted with regions of the 1a protein
      containing putative helicase and methyltransferase domains respectively. Two
      other inhibitory antibodies mapped to a region of the 2a protein containing the
      GDD motif which is highly conserved in RdRps. Prior interaction of the latter
      antibodies with a peptide containing the GDD motif prevented the antibody
      mediated inhibition of the replicase. Polyclonal antibodies which inhibited the
      RdRp activity of the replicase complex were also produced using peptides
      corresponding to conserved helicase and polymerase motifs in the 1a and 2a
      proteins. The greatest inhibition was shown by antibodies to a peptide containing
      the GDD motif. These results demonstrate the functional importance of the
      identified sequence motifs in CMV RNA replication and indicate that the motifs
      are located in the replicase complex at positions accessible to antibodies,
      consistent with roles in interacting with the RNA template, RNA primer and enzyme
      substrates.

PMID- 7525865
TI  - Measurement of antibody avidity for hepatitis C virus distinguishes primary
      antibody responses from passively acquired antibody.
AB  - A new IgG antibody avidity test for hepatitis C virus (HCV) has been developed
      and was validated using sera from 12 renal dialysis patients infected with HCV.
      In primary HCV infection low avidity antibody (mean avidity index 24%) was
      detected within 50 days of seroconversion whereas in long-term infection (at
      least 300 days after seroconversion), the mean avidity index was high (88%); in
      five patients, the avidity index was shown to increase rapidly as time elapsed
      after primary infection, whereas immunosuppressive therapy was found to delay
      maturation of the immune response in two further patients. The assay was then
      employed to confirm that a spurious outbreak of primary HCV infection in eight
      bone marrow transplant patients was explicable by passive acquisition of high
      avidity anti-HCV after intravenous immunoglobulin therapy. It is concluded that
      this avidity test will have an important role in the investigation of HCV
      infection in patients.

PMID- 7525863
TI  - Expression of the Epstein-Barr virus envelope fusion glycoprotein gp85 gene by a
      recombinant baculovirus.
AB  - The gp85 envelope glycoprotein of Epstein-Barr virus (EBV) has a role in the
      molecular mechanism of infection, enabling fusion between the viral and host cell
      envelopes, a role in common with the homologous gH glycoproteins in other
      herpesviruses. A glutathione S-transferase bacterial fusion protein (GST85N-S)
      was generated, containing 178 amino acids from the C terminus of gp85 and
      including a known gp85 linear epitope. A panel of EBV-positive human antisera
      contained no antibodies to linear epitopes presented on the purified GST85N-S
      protein, indicating that primary protein structure in this region of gp85 is not
      a B cell target. This bacterial fusion protein was used to raise a rabbit
      monospecific polyclonal antiserum capable of detecting gp85 in a Western blot.
      The majority of recombinant baculovirus-expressed gp85 obtained from cell
      extracts prepared with SDS appeared on Western blots as heterogeneous high M(r)
      protein aggregates and consistently included 84K, 81K and 70K bands. Recombinant
      gp85 aggregation was increased by boiling the sample prior to gel
      electrophoresis. The 84K and 81K proteins were completely sensitive to
      endoglycosidase H treatment, indicating that these glycosylated species did not
      undergo further post-translational processing. Immunofluorescence studies
      revealed that recombinant gp85 was not transported to the insect cell surface. It
      reacted only with antibodies recognizing denatured gp85 and not with antibody to
      native gp85. Therefore expression of the gene encoding gp85, BXLF2, alone in the
      baculovirus expression system is insufficient for the synthesis of a correctly
      transported, processed, folded and antigenically native form of recombinant gp85.

PMID- 7525864
TI  - Antibodies to hepatitis E virus among Chinese patients with acute hepatitis in
      Taiwan.
AB  - The prevalence of antibodies to hepatitis E virus (anti-HEV) was investigated in
      patients with acute hepatitis, and correlated with the clinical features. Sera
      from 110 patients with acute hepatitis and 60 healthy controls were tested for
      anti-HEV, antibody to hepatitis C virus (anti-HCV), and hepatitis B surface
      antigen (HBsAg). There were significant differences in the prevalence of anti
      HEV, anti-HCV, and HBsAg between patients and controls (21.8% vs. 0%, 16.3% vs.
      1.6% and 58.1% vs. 18.0%, respectively). Anti-HEV was detected in 6 (25.0%) of 24
      patients with anti-HCV, 6 (9.3%) of 64 patients with HBsAg, and another 6 (22.2%)
      of 27 patients with acute hepatitis non-A, non-B, non-C. Anti-HEV was found in 15
      men and three women, whose ages ranged from 34 to 75 (median, 57) years old. The
      median age of patients with anti-HEV was older than that in patients without this
      antibody (57 vs. 38 years; P = 0.001). The prevalence of anti-HEV in patients
      with anti-HCV alone (35.2%) was higher than that (11.1%) in patients with HBsAg
      alone (P = 0.03). Compared to patients without anti-HEV, HEV-infected patients
      had a higher frequency of travel to a foreign country (P = 0.0001), had a lower
      HBsAg rate (P = 0.019), and had higher serum alkaline phosphatase levels (P =
      0.04) and gamma-glutamyl transpeptidase levels (P = 0.01). In conclusion, HEV
      infection occurs in 22.2% of patients with acute hepatitis non-A, non-B, non-C.
      HEV superinfection may occur in patients with chronic hepatitis B or C virus
      infection.

PMID- 7525866
TI  - Different antibody response to a neutralizing epitope of human cytomegalovirus
      glycoprotein B among seropositive individuals.
AB  - The amino-terminal portion of human cytomegalovirus glycoprotein B (HCMV-gB) was
      expressed as a fusion protein to analyze the neutralizing epitope recognized by
      human monoclonal antibody C23 and the humoral immune response to this epitope.
      The linear neutralizing epitope was further localized to the peptide within 17
      amino acids (position 68-84) which were conserved between two HCMV laboratory
      strains. Ten out of 17 HCMV-seropositive human sera contained the antibody
      against this epitope. Although seven sera were negative for reacting with the
      fusion protein, the viruses isolated from the same patients retained the epitope.
      The immunogenicity of the epitope and the possible application of C23 human
      monoclonal antibody for passive immunization against HCMV infections are
      discussed.

PMID- 7525867
TI  - Antigenic determinant properties of neurofibrillary tangles. Relevance to
      progressive supranuclear palsy.
AB  - Neuronal cytoskeleton is composed of microfilaments, neurofilaments and
      microtubules which show distinctive ultrastructural characteristics. Different
      groups of antibodies against neurofilaments and microtubule associated proteins
      which were grouped according to their specificity for proteins of perykarium,
      axons and/or dendrites have been produced. A 8.6 kD polypeptide called ubiquitin
      has been recognized as one of the heat shock proteins. Ubiquitin is implicated in
      the non-lysosomal degradation of abnormal proteins and other proteolytic
      intracellular mechanisms. Several immunohistological studies on Alzheimer's
      disease (AD)-neurofibrillary tangles (NFTs) demonstrated that antibodies for
      different normal cytoskeletal components bind to NFTs-bearing neurons. AD-NFTs
      could be also demonstrated using antibodies for the beta-amyloid protein. The
      production and accumulation of abnormal proteins such as those observed in AD
      NFTs induce a ubiquitin-mediated degradative pathway to remove them. It has been
      demonstrated that ubiquitin is covalently associated with insoluble
      neurofibrillary material of AD-NFTs. Topographical differences in the
      distribution of NFTs underscore that different neuronal populations including
      neocortical neurones are affected in progressive supranuclear palsy (PSP) and AD.
      Differences in the molecular composition of PSP-NFTs highlighted by
      immunochemical studies induce us to speculate that different physio- and
      aetiopathogenetic mechanisms are operative in the production of PSP-NFTs.

PMID- 7525869
TI  - Differential neural regulation of a neuromuscular junction-associated antigen in
      muscle fibers and Schwann cells.
AB  - Monoclonal antibodies 3G2 and 4E2 recognize a postsynaptic component of rat
      neuromuscular junctions. In contrast to many other postsynaptic junctional
      antigens, expression of this antigen is nerve-dependent: immunoreactivity
      disappears from junctions following denervation and returns upon reinnervation
      (Astrow et al., 1992 J. Neurosci. 12:1602-1615). Here we show that the epitope is
      also expressed by Schwann cells and that this expression is also neurally
      regulated. Weak mAb 3G2/4E2 immunoreactivity was found in myelinating Schwann
      cells but was not detected in either nonmyelinating Schwann cells or in terminal
      Schwann cells at the neuromuscular junction. Following axotomy, immunoreactivity
      increased in myelinating Schwann cells, and nonmyelinating and terminal Schwann
      cells became immunopositive. Moreover, the immunoreactivity in terminal Schwann
      cells revealed their extensive sprouting in response to denervation (Reynolds and
      Woolf, 1992, J. Neurocytol. 21: 50-66). After nerve regeneration, mAb 3G2/4E2
      immunoreactivity in all Schwann cells returned towards normal: it disappeared
      from terminal Schwann cells, returned to low levels in myelinating Schwann cells,
      and decreased in nonmyelinating Schwann cells. Immunoblots of axotomized nerve
      and cultured muscle fibers revealed the same set of immunoreactive bands.
      Therefore, Schwann cells and muscle fibers share the expression of an epitope
      that is under neural control, but is regulated differently at each site. In
      Schwann cells, the presence of the nerve suppresses expression of the epitope,
      whereas in muscle fibers, the nerve terminal promotes this expression. The
      differential regulation of mAb 3G2/4E2 immunoreactivity in terminal Schwann cells
      and muscle fibers suggests that the epitope may be involved in interactions
      between nerve terminals and these cells.

PMID- 7525870
TI  - Sequencing and promoter analysis of the genomic region between the rat neuronal
      nicotinic acetylcholine receptor beta 4 and alpha 3 genes.
AB  - Nicotinic acetylcholine receptors (nAChRs) found on neurons are composed of
      ligand binding (alpha) and structural (beta) subunits. Different combinations of
      alpha and beta subunits produce nAChR subtypes with different pharmacological and
      ion-conducting properties. Transcriptional regulation may be an important
      determinant of receptor subtype in a neuronal population and thus influence
      transmission through a ganglion or group of neurons in the CNS by controlling the
      nAChR subtype(s) present. In order to understand the transcriptional regulation
      of neuronal nAChRs by cell contact and electrical activity, it will be first
      necessary to identify DNA elements that control the expression of members of this
      family and to identify factors required for the expression of these genes. In
      this report we have begun to examine the 5'-flanking region of one member of the
      nAChR family of genes, alpha 3. We have sequenced the region between the beta 4
      and alpha 3 genes and have identified two promoter regions in the beta 4-alpha 3
      intergenic region. One region is close to the beta 4 gene downstream of exon 6
      and has strong promoter activity in both orientations; the other is close to the
      start of the alpha 3 gene coding region. A region with putative silencer activity
      is also found near the upstream promoter. This bidirectional promoter region
      could be involved in the control of alpha 3 and beta 4 gene expression.

PMID- 7525872
TI  - In vitro analyses of neurite outgrowth indicate a potential role for tenascin
      like molecules in the development of insect olfactory glomeruli.
AB  - Tenascin-like material is associated with glial cells that form borders around
      developing glomerular units in the olfactory (antennal) lobe of the moth Manduca
      sexta and is present at critical stages of glomerulus formation (Krull et al.,
      1994, J. Neurobiol. 25:515-534). Tenascin-like immunoreactivity declines in the
      mature lobe, coincident with a wave of synapse formation within the glomeruli and
      glomerulus stabilization. Tenascin-like molecules associated with neuropilar glia
      are in the correct position to influence the branching patterns of growing
      neurites by constraining them to glomeruli. In this study, we examine the growth
      of cultured moth antennal-lobe neurons in response to mouse CNS tenascin. Uniform
      tenascin provides a poor substrate for cell-body attachment and neurite
      outgrowth. Neuronal cell bodies provided with a striped substratum consisting of
      tenascin and concanavalin-A (con-A)/laminin attach preferentially to con
      A/laminin lanes. Most neurons restrict their branching to con-A/laminin lanes
      both at early and later times in culture but others send processes across
      multiple tenascin and con-/laminin lanes in an apparently indiscriminate manner.
      Tenascin can inhibit the neuritic outgrowth of most antennal-lobe neurons, and
      this raises the possibility that the tenascin-like molecules associated with
      neuropilar glia in vivo act to constrain growing neurites to glomeruli. Thus,
      glial cells, acting in concert with olfactory axons, might act to promote
      glomerular patterns of branching by antennal-lobe neurons.

PMID- 7525871
TI  - Reciprocal regulation of estrogen and NGF receptors by their ligands in PC12
      cells.
AB  - Recent work has shown that estrogen receptor mRNA and protein co-localize with
      neurotrophin receptor systems in the developing basal forebrain. In the present
      study we examined the potential for reciprocal regulation of estrogen and
      neurotrophin receptor systems by their ligands in a prototypical neurotrophin
      target, the PC12 cell. Using in situ hybridization histochemistry, RT-PCR and a
      modified nuclear exchange assay, we found both estrogen receptor mRNA and
      estrogen binding in PC12 cells. Moreover, while estrogen binding was relatively
      low in naive PC12 cells, long-term exposure to NGF enhanced estrogen binding in
      these cells by sixfold. Furthermore, concurrent exposure to estrogen and NGF
      differentially regulated the expression of the two NGF receptor mRNAs. The
      expression of trkA mRNA was up-regulated, while p75NGFR mRNA was down-regulated
      transiently. The present data indicate that NGF may increase neuronal sensitivity
      to estrogen, and that estrogen, by differentially regulating p75NGFR and trkA
      mRNA, may alter the ratio of the two NGF receptors, and, consequently,
      neurotrophin responsivity. In view of the widespread co-localization of estrogen
      and neurotrophin receptor systems in the developing CNS, the reciprocal
      regulation of these receptor systems by NGF and estrogen may have important
      implications for processes governing neural maturation and the maintainance of
      neural function.

PMID- 7525868
TI  - Alterations of neurotransmitter receptors and neurotransmitter transporters in
      progressive supranuclear palsy.
AB  - Neurotransmitter receptors and neurotransmitter transporters were studied
      postmortem in the brains of 9 PSP patients by receptor autoradiography. Densities
      of dopamine uptake sites and neurotensin receptors were significantly reduced in
      striatum and substantia nigra consistent with a localization of these binding
      sites on degenerating dopaminergic nigrostriatal projection neurons. The
      densities of dopamine D1 receptors were unchanged. Dopamine D2 receptors were
      unaltered when labeled by [125I]-Iodosulpride or [3H]-CV 205 502, but appeared to
      be significantly reduced when labeled by [3H]-spiperone. Levels of D2 mRNA were
      comparable to control levels, suggesting that only subtypes of Dopamine D2-like
      receptors may be affected in PSP. Serotonin (5-HT) uptake sites and 5-HT
      receptors were not altered. The density of muscarinic receptors was reduced in
      striatum, possibly related to a degeneration of cholinergic striatal
      interneurons, but increased in internal globus pallidus. GABAA/BZ receptor
      binding sites were significantly reduced in both segments of globus pallidus,
      probably as a consequence of severe degeneration of intrinsic pallidal neurons in
      PSP. Binding of substance P in striatum tended to be decreased but failed to
      reach statistical significance. Compared to Parkinson's disease, the densities of
      more neurotransmitter receptors were altered in PSP. With the exception of
      increased muscarinic receptor binding sites in medial globus pallidus, the
      alterations seen in PSP seem to reflect cell loss rather than functional changes.

PMID- 7525873
TI  - Partial structure and mapping of the human myelin P2 protein gene.
AB  - The myelin P2 protein, a 14,800-Da cytosolic protein found primarily in
      peripheral nerves, belongs to a family of fatty acid binding proteins. Although
      it is similar in amino acid sequence and tertiary structure to fatty acid binding
      proteins found in the liver, adipocytes, and intestine, its expression is limited
      to the nervous system. It is detected only in myelin-producing cells of the
      central and peripheral nervous systems, i.e., the oligodendrocytes and Schwann
      cells, respectively. As part of a program to understand the regulation of
      expression of this gene, to determine its function in myelin-producing cells, and
      to study its role in peripheral nerve disease, we have isolated and characterized
      overlapping human genomic clones encoding the P2 protein. We report here on the
      partial structure of this gene, and on its localization within the genome. By
      using a panel of human-hamster somatic cell hybrids and by in situ hybridization,
      we have mapped the human P2 gene to segment q21 on the long arm of chromosome 8.
      This result identifies the myelin P2 gene as a candidate gene for autosomal
      recessive Charcot-Marie-Tooth disease type 4A.

PMID- 7525875
TI  - Paralytic tremor (pt): a new allele of the proteolipid protein gene in rabbits.
AB  - Paralytic tremor (pt) is a sex-linked mutation in rabbit that affects myelination
      of the CNS. Myelin in the pt brains represents approximately 30% of the normal
      levels. Previously we showed that the pt mutation affects primarily proteolipid
      protein (Plp) gene expression. In the present study we investigated the relative
      effect of the pt mutation on two distinctive Plp gene products, PLP- and DM-20
      specific messenger RNAs. Our results showed that both PLP and DM-20 are affected
      and that the ratio DM-20/PLP was higher in pt rabbits than in age-matched
      controls. We sequenced normal rabbit PLP cDNA and characterized pt mutation at
      the DNA level. Rabbit PLP sequence, deduced from cDNA, differs from the human
      protein only at Thr198. Sequence analysis of the mutant cDNA revealed a
      transversion T-->A in exon 2 of the Plp gene. This point mutation, which is
      placed at the end of the first potential transmembrane domain, results in a
      substitution of His36 by a glutamine. This transversion abolishes a restriction
      site that enabled us to screen a large number of animals and observe a perfect
      correlation between the pt allele and the abnormal phenotype.

PMID- 7525874
TI  - Carbohydrate structures of beta-trace protein from human cerebrospinal fluid:
      evidence for "brain-type" N-glycosylation.
AB  - The carbohydrate structures of beta-trace protein from human cerebrospinal fluid
      have been elucidated. This protein carries exclusively N-linked oligosaccharides
      at two sites (Asn29 and Asn56). Enzymatically released N-glycans were studied by
      compositional and methylation analyses, high-pH anion-exchange chromatography,
      and liquid secondary ion mass spectrometry. All glycans were found to be of the
      complex type, and most (90%) of them were biantennary with no (40%), one (40%),
      or two (20%) N-acetylneuraminic acid residues. The rest were triantennary chains
      or biantennary chains with intact or truncated lactosamine repeats. The innermost
      N-acetylglucosamine residues of nearly all structures were found to be alpha 1,6
      fucosylated. Peripheral fucose (about 20% alpha 1,3-linked to N
      acetylglucosamine) was also detected. Seventy percent of the oligosaccharides
      contained a bisecting N-acetylglucosamine. Especially in the neutral, but also in
      the monosialylated oligosaccharide fractions, many incomplete antennae consisting
      of N-acetylglucosamine only were present. At least 20 different N-glycans were
      identified. Analysis of the site-specific glycosylation patterns at Asn29 and
      Asn56 revealed only minor differences. According to the structural features (a
      high degree of fucosylation, high amounts of bisecting N-acetylglucosamine, as
      well as terminal N-acetylglucosamine and galactose residues, and significant
      amounts of N-acetylneuraminic acid in alpha 2,3 linkage), this protein can be
      classified as "brain-type" glycosylated.

PMID- 7525876
TI  - Localization of specific epitopes on human microtubule-associated protein 2.
AB  - Microtubule-associated protein 2 (MAP-2) is an abundant neuronal cytoskeletal
      protein that binds to tubulin and stabilizes microtubules. Using fusion protein
      constructs we have defined the epitopes of 10 monoclonal antibodies (mAbs) to
      discrete regions of human MAP-2. Proteins were expressed in pATH vectors. After
      electrophoresis, immunoblotting was performed. By western blot analysis five of
      the mAbs (AP-14, AP-20, AP-21, AP-23, and AP-25) share epitopes with only the
      high molecular weight isoforms (MAP-2a, MAP-2b); two of the mAbs (AP-18 and tau
      46) recognize MAP-2a, MAP-2b, and MAP-2c. Although AP-18 immunoreactivity was
      detected within heat-stable protein homogenates isolated from a human
      neuroblastoma cell line MSN, fusion protein constructs encompassing human MAP-2
      were negative, suggesting that the AP-18 epitope is phosphorylated. Furthermore,
      AP-18 immunoreactivity was lost after alkaline phosphatase treatment of heat
      stable protein preparations from MSN cells. Four of the mAbs (322, 636, 635, and
      39) recognize epitopes located within amino acids 169-219 of human MAP-2. AP-21
      maps to a region between amino acids 553 and 645. AP-23 maps between amino acids
      645 and 993, whereas AP-20, AP-14, and AP-25 map between amino acids 995 and
      1332. Expression of the region of MAP-2 between amino acids 1787 and 1824 was
      positive to tau 46.

PMID- 7525877
TI  - Changes in the tyrosine phosphorylation of mitogen-activated protein kinase in
      the rat hippocampus during and following severe hypoglycemia.
AB  - The changes in the levels of tyrosine-phosphorylated proteins in the cytosolic
      fraction of the rat hippocampus subjected to severe hypoglycemia were analyzed. A
      marked increase in tyrosine phosphorylation of a 43-kDa protein was observed at
      30 min of isoelectric EEG and 30 min and 1 h of recovery. Immunostaining of the
      same blot with antibody against mitogen-activated protein (MAP) kinase
      demonstrated a double band of approximately 42 and 43 kDa. The increased tyrosine
      phosphorylation of MAP kinase during hypoglycemic coma and the early recovery
      period suggests that MAP kinase may be involved in neuronal degeneration and
      repair.

PMID- 7525878
TI  - New lignans from Anogeissus acuminata with HIV-1 reverse transcriptase inhibitory
      activity.
AB  - Anolignan A [1] and anolignan B [3] are new dibenzylbutadiene lignans isolated
      from Anogeissus acuminata. Compounds 1 and 3 were identified as the active HIV-1
      reverse transcriptase (RT) inhibitory constituents of this plant obtained by
      bioassay-guided fractionation. Compound 3, which was very weakly active when
      tested alone, showed high activity when combined with 1. The activity of 1 was
      likewise enhanced in the presence of 3. A concave isobole obtained from a plot of
      data derived from assays with 1 and 3 in combination indicated their synergistic
      effects. Another new lignan, anolignan C [5], and a known lignan, (-)
      secoisolariciresinol [10], were also isolated from this plant. Compounds 5 and 10
      did not have activity against HIV-1 RT. Compounds 1, 3 and 5 were either weakly
      cytotoxic or noncytotoxic when tested in various cancer cell lines. The
      structures of 1-5 and 10 were established by spectroscopic methods, especially by
      1D and 2D nmr experiments.

PMID- 7525879
TI  - Point mutations in mitochondrial tRNA genes: sequence analysis of chronic
      progressive external ophthalmoplegia (CPEO)
AB  - We have sequenced all mitochondrial tRNA genes from 9 Japanese patients with
      chronic progressive external ophthalmoplegia (CPEO) who had no detectable large
      mtDNA deletions nor mutations previously reported, and identified 6 different
      base substitutions in 6 patients. Since 5 of the 6 substitutions were homoplasmic
      in distribution and recognizable in some normal controls, they were thought to be
      polymorphisms in normal individuals. One mutation at nucleotide (nt) 12311 in the
      tRNA(Leu(CUN)) gene was not present in 90 normal controls nor in 103 patients
      with other mitochondrial myopathies. This mutation was in a heteroplasmic state,
      and the mutated site was conserved among other species during evolution,
      suggesting a disease-related mutation. However, the significance of this mutation
      has to be studied further. In Japanese CPEO patients without large deletions, a
      point mutation in the mitochondrial tRNA gene is not likely to be a frequent
      cause.

PMID- 7525881
TI  - Structural comparison of NK2 receptor agonists and antagonists.
AB  - The conformational space of two NK2 receptor agonists and a new potent antagonist
      has been sampled by the simulated annealing technique. Low-energy conformers were
      obtained, which were compared with respect to their key residues, namely
      phenylalanine, leucine and methionine. The hypothesis is that they share part of
      the binding site on the receptor.

PMID- 7525882
TI  - Breast cancer prevention education at a shopping center in Israel: a student
      nurse community health project.
AB  - Community health nursing at the baccalaureate level emphasizes health prevention
      education. With this focus in view, fourth-year students at a nursing school in
      Israel were required to organize, present, and evaluate a health fair. One of the
      subjects presented was breast cancer prevention and early detection. To implement
      their project, students employed health marketing, educational, and
      communicational skills. The breast cancer booth, located at a shopping center,
      served 200 women and 7 men with information on prevention and early detection
      over a period of about 3 hr. The health fair design, execution, and evaluation
      successfully met the course goals. In addition, a large public was reached, much
      interest was displayed, and positive feedback was received.

PMID- 7525880
TI  - A study of apoptosis in normal and pathologic nervous tissue after in situ end
      labeling of DNA strand breaks.
AB  - Programmed cell death (PCD) via apoptosis is characterized by nuclear pyknosis
      and fragmentation, and biochemically by oligonucleosomal cleavage of DNA.
      Apoptosis occurs in the developing nervous system, whereas its role in
      neurodegenerative diseases is still debated. Recognition of apoptotic cells has
      recently been facilitated by in situ end-labeling (ISEL) techniques which
      identify DNA strand breaks through incorporation of labeled nucleotides. We have
      applied two ISEL assays to physiological and pathological conditions affecting
      the nervous system in which PCD is likely to occur. Terminal transferase assay
      was more sensitive than DNA polymerase assay and allowed the recognition of a
      larger number of cells than conventional histology. Apoptotic cells were readily
      found in the developing spinal cord and dorsal root ganglia. Medulloblastomas,
      gliomas, brain lymphomas and metastases showed abundant apoptotic cells either
      isolated or grouped in small foci. Labeling was also found in cells without a
      clearcut apoptotic morphology. Apoptotic cells were not found in Alzheimer's
      disease, amyotrophic lateral sclerosis and human and mouse prionic
      encephalopathies. Our results show that ISEL is a useful technique for
      demonstrating apoptotic cells in nervous tissue during development and in brain
      tumors. Lack of staining in neurodegenerative diseases suggests that other types
      of PCD might be involved.

PMID- 7525883
TI  - Significant activity of paclitaxel in advanced transitional-cell carcinoma of the
      urothelium: a phase II trial of the Eastern Cooperative Oncology Group.
AB  - PURPOSE: To assess the efficacy and toxicity of single-agent paclitaxel as first
      line chemotherapy in patients with locally advanced or metastatic transitional
      cell carcinoma of the urothelium. PATIENTS AND METHODS: Twenty-six eligible
      patients were enrolled onto this cooperative group study and treated with
      paclitaxel at a dosage of 250 mg/m2 by 24-hour continuous infusion every 21 days
      until progression or patient intolerance. All patients received recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) at 5 micrograms/kg/d for at least
      10 days during each cycle. RESULTS: Eleven of 26 patients (42%; 95% confidence
      interval [CI], 23% to 63%) demonstrated an objective response, with seven
      achieving a complete clinical response (CR) (27%; 95% CI, 12% to 48%) and four
      (15%) a partial response (PR). The median duration of response in the 11
      responders is 7+ months (range, 4 to 17), with five responders (four CRs, one PR)
      remaining progression-free at 5, 6, 10, 12, and 16 months from the start of
      therapy. The estimated median survival duration for all patients is 8.4 months.
      Hematologic toxicity consisted of anemia (12% grade 3) and granulocytopenia (4%
      grade 3, 19% grade 4), with two patients developing granulocytopenic fevers.
      Nonhematologic toxicity included grade 3 mucositis in 11%, grade 3 neuropathy in
      11%, and grade 4 diarrhea in 4%. CONCLUSION: Single-agent paclitaxel at this
      dosage and schedule is one of the most active single agents in previously
      untreated patients with advanced urothelial carcinoma, and is well tolerated by
      this patient population when given with hematopoetic growth factor support.

PMID- 7525885
TI  - Phase II trial of paclitaxel shows antitumor activity in patients with previously
      treated germ cell tumors.
AB  - PURPOSE: A trial of paclitaxel was conducted in patients with previously treated
      germ cell tumors (GCT). As the identification of new agents in GCT may be
      compromised by restricting entry criteria to heavily pretreated patients, an
      alternative trial design was used in which eligibility was restricted to patients
      with limited prior therapy. PATIENTS AND METHODS: Patients were eligible if their
      prior therapy was limited to one cisplatin-based regimen or < or = six cycles of
      prior cisplatin-based therapy. Paclitaxel 250 mg/m2 was administered by
      continuous infusion over 24 hours every 21 days. The dose of paclitaxel was
      modified for each patient based on toxicity. Granulocyte colony-stimulating
      factor (G-CSF) 5 micrograms/kg/d was administered during nadir periods. RESULTS:
      Thirty-one patients were treated; eight patients (26%) achieved a partial (n = 5)
      or a complete (n = 3) response. Responses were achieved in patients who had
      failed to respond to treatment with cisplatin, ifosfamide, and etoposide, and in
      patients with poor prognostic features, ie, mediastinal primary tumor site and
      patients with a best prior response of an incomplete response to cisplatin
      therapy. One complete responder remains continuously free of disease at 13+
      months and one of the five patients who achieved a partial response remains
      progression-free at 14+ months. CONCLUSION: Paclitaxel has antitumor activity in
      GCT and warrants continued study in combination chemotherapy. Phase I/II trials
      will address its role in combination with cisplatin and ifosfamide and as a part
      of dose-intensive therapy. Furthermore, the study showed that a trial design in
      which eligibility criteria limits prior therapy was feasible, resulted in the
      identification of antitumor activity in a new agent, and may be considered in
      future trials for other promising new agents in GCT.

PMID- 7525886
TI  - Intensified concomitant chemoradiotherapy with and without filgrastim for poor
      prognosis head and neck cancer.
AB  - PURPOSE: We previously demonstrated high locoregional control rates in patients
      with poor-prognosis head and neck cancer using fluorouracil (5-FU), hydroxyurea
      (HU), and concomitant radiotherapy (FHX). In two trials reported here, we added
      cisplatin with and without granulocyte colony-stimulating factor (G-CSF) to 5-FU,
      HU, and concomitant radiotherapy. PATIENTS AND METHODS: Eligible patients had
      failed to respond to prior local therapy (group 1); previously untreated patients
      with unresectable and/or metastatic disease and a projected 2-year survival rate
      less than 10% were also eligible (group 2). Chemoradiotherapy consisted of 1.8 to
      2.0 Gy on days 1 to 5 with simultaneous infusional 5-FU at 800 mg/m2/d and HU
      administered every 12 hours for 11 doses at escalating doses. Cisplatin was
      administered at 100 mg/m2 during every other cycle. Cycles were repeated every 14
      days until completion of radiotherapy. In study 2, G-CSF was added on days 6 to
      13 at 5 micrograms/kg/d. RESULTS: Acute and cumulative myelosuppression limited
      the feasibility of adding cisplatin to FHX without G-CSF. G-CSF allowed for
      escalation of HU to 1 g orally every 12 hours without dose-limiting acute
      toxicity during cycles 1 and 2. Dose-limiting cumulative toxicity consisted of
      severe or life-threatening myelosuppression and mucositis. To decrease total
      treatment duration and, thus, cumulative toxicity, a hyperfractionated radiation
      therapy schedule was investigated using the established chemotherapy doses with
      1.5 Gy twice daily on days 1 to 5 (75 Gy over five treatment cycles). No increase
      in acute toxicities was seen; cumulative toxicities remained frequently severe or
      life-threatening. Thirty-eight of 45 assessable patients responded. The median
      survival duration was 12 months for both groups. Median time to treatment failure
      was 8 months for group 1 and has not been reached for group 2. At 1 year, local
      control rates were 74% and 91% for groups 1 and 2, respectively. CONCLUSION: The
      addition of cisplatin to 5-FU, HU, and concomitant radiotherapy is feasible using
      G-CSF. The high locoregional control rate and failure-free interval justify
      further investigation of this regimen in previously untreated patients.

PMID- 7525884
TI  - Phase II trial of vinblastine, ifosfamide, and gallium combination chemotherapy
      in metastatic urothelial carcinoma.
AB  - PURPOSE: Phase II trial in metastatic urothelial carcinoma using a novel
      combination chemotherapy regimen consisting of vinblastine, ifosfamide, and
      gallium nitrate (VIG). PATIENTS AND METHODS: Twenty-seven patients were entered
      onto this phase II study. Dosages were vinblastine 0.11 mg/kg days 1 and 2,
      ifosfamide 1.2 gm/m2 days 1 through 5 (with mesna), and gallium 300 mg/m2 as a 24
      hour infusion days 1 through 5, with calcitriol (1,25-dihydroxycholecalciferol)
      0.5 microgram/d orally starting 3 days before each course (except the first) and
      continuing throughout gallium administration, plus recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) (filgrastim) 5 micrograms/kg/d days 7 through
      16. Courses were repeated every 21 days for a maximum of six cycles. RESULTS: The
      major toxicity was granulocytopenia. Fifteen patients (55.6%) had grade 3 or 4
      granulocytopenia, including eight patients with granulocytopenic fevers. Eleven
      patients had grade 3 or 4 anemia and four had grade 3 or 4 nephrotoxicity, which
      was reversible. Other grade 3 to 4 toxicities included hypocalcemia (three
      patients), thrombocytopenia (two), encephalopathy (one), and temporary blindness
      (one). There was one treatment-related mortality. Toxicity was more severe in
      patients older than 70 years and those with prior pelvic irradiation, prior
      cisplatin adjuvant therapy, or prior nephrectomy. We now decrease VIG by 20% in
      this patient population. Eighteen patients (67%) achieved an objective response,
      including 11 (41%) who attained a disease-free status (five with VIG alone and
      six with subsequent surgery). Median duration of remission was 20 weeks, with
      five patients still in remission at 22+ to 56+ weeks. CONCLUSION: VIG combination
      chemotherapy is very active in patients with metastatic urothelial carcinoma.
      Toxicity was significant but manageable.

PMID- 7525889
TI  - An adult patient with cerebellar ganglioglioma.
AB  - We encountered a very rare patient with cerebellar ganglioglioma. To our
      knowledge, there are 17 reported patients with this disease, of whom ours (a 53
      year-old male) was the oldest. The tumor was totally resected, but radiotherapy
      was also performed to prevent recurrence. He is completely symptom-free 9 months
      after operation.

PMID- 7525887
TI  - The role of tissue inhibitor of metalloproteinase-1 in specific aspects of cancer
      progression and reproduction.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are specific inhibitors of the
      multi member family of matrix metalloproteinases (MMPs). Since MMP function is
      fundamental to events that require tissue remodelling, TIMPs regulate normal
      biological processes by inhibiting MMPs, and are of importance in pathological
      conditions. In this chapter we review evidence for the suppressive role of TIMP-1
      in the malignant progression of cancer and of its regulatory function in
      controlling invasion during blastocyst implantation and development.

PMID- 7525891
TI  - A hyperpolarization-activated cation conductance in lobster olfactory receptor
      neurons.
AB  - 1. The current underlying inward rectification in lobster olfactory receptor
      neurons was investigated with the use of whole-cell patch-clamp techniques.
      Inward rectification could most likely result from an inwardly rectifying
      potassium conductance or a hyperpolarization-activated cation conductance. To
      distinguish between these possibilities, the current underlying inward
      rectification was examined with respect to its sensitivity to extracellular Cs+
      and Ba2+, time course of activation, and reversal potential. 2. In current clamp,
      injection of negative current led to a hyperpolarization followed by a partial
      return (sag) toward the initial holding potential. The rate and magnitude of the
      sag depended on the magnitude of the hyperpolarizing current with larger currents
      leading to larger, faster depolarizing sags. In voltage clamp, hyperpolarizing
      steps elicited a slowly activating, noninactivating inward current clamp. Both
      the sag and the slow inward current were blocked reversibly by extracellular
      application of 5 mM CsCl but were unaffected by 2 mM BaCl2. 3. The rate of inward
      current activation was best approximated by a single exponential function with
      time constants that were voltage dependent, ranging from 7.8 s at -69 mV to 248
      ms at -114 mV. 4. Cells normally exhibited an average input resistance of 0.99 G
      omega over the range of -69 to -114 mV. With the hyperpolarization-activated
      inward current blocked by 5 mM CsCl, the average input resistance increased to
      2.12 G omega over the same range. 5. Analysis of tail currents revealed that the
      average predicted reversal potential of the hyperpolarization-activated inward
      current was 1.7 mV and was not affected significantly by a shift in ECl.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7525890
TI  - Chondroid chordoma versus low-grade chondrosarcoma of the base of the skull: can
      immunohistochemistry resolve the controversy?
AB  - The classification of cartilaginous tumors of the skull base, including chondroid
      chordoma and chondrosarcoma remains the subject of controversy. Critical review
      of the literature and our own experience of chordomas and cartilaginous tumors of
      the skull base led to the following conclusions: 1) Chondrosarcoma of the skull
      base is a distinct clinicopathological entity. The immunohistochemical staining
      pattern (cytokeratin negative, epithelial membrane antigen (EMA) negative) can be
      helpful in distinguishing it from chordoma with chondroid differentiation
      (cytokeratin positive, EMA positive). 2) The chondroid chordomas originally
      described by Heffelfinger et al. may have included some true chondrosarcomas with
      focal areas of myxoid chordomalike appearance. 3) Focal chondroid differentiation
      in chordoma is not such a rare phenomenon. Further study is needed to define
      whether chordoma with chondroid foci should be separated out from conventional
      chordoma as a distinct entity with a better prognosis.

PMID- 7525892
TI  - N-type Ca2+ channels are located on somata, dendrites, and a subpopulation of
      dendritic spines on live hippocampal pyramidal neurons.
AB  - In the nervous system the influx of Ca2+ orchestrates multiple biochemical and
      electrical events essential for development and function. A major route for Ca2+
      entry is through voltage-dependent calcium channels (VDCCs). It is becoming
      increasingly clear that the precise contribution VDCCs make to neuronal function
      depends not only upon their specific electrophysiological properties but also on
      their distribution over the nerve cell surface. One location where the presence
      of VDCCs may be critical is the dendritic spine, a structure known to be the
      major site of excitatory synaptic input. On spines, VDCCs are hypothesized to
      play an essential role in signal processing, learning, and memory. However,
      direct evidence for the presence of VDCCs on spines is lacking. Attempts to
      examine the distribution of VDCCs, or indeed any other components, on spines have
      been hampered since the size of many spines is close to the limits of resolution
      of conventional light microscopy. Using a new, biologically active, fluorescein
      conjugate of omega-conotoxin (Fl-omega-CgTx), a selective blocker of N-type
      VDCCs, and confocal microscopy, we have mapped the distributions of N-type VDCCs
      on live CA1 neurons in rat hippocampal slices. VDCCs were found on somata,
      throughout the dendritic arbor, and on dendritic spines in all hippocampal
      subfields. A comparison of three-dimensional reconstructions of structures
      labeled by Fl-omega-CgTx with those outlined by 1,1-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine (Dil) or Lucifer yellow confirmed the presence of N
      type VDCCs on dendritic spines. However, spine frequency on dendrites labeled
      with Fl-omega-CgTx was much lower than the spine frequency on dendrites labeled
      with Lucifer yellow or Dil, suggesting that some spines lack N-type VDCCs. These
      results offer the first direct evidence for the localization of any voltage
      dependent channel on dendritic spines. The presence of N-type VDCCs on dendrites
      and their spines argues that these channels may participate in the generation of
      active Ca2+ conductances in distal dendrites, and is consistent with a role for
      spines as specialized compartments for concentrating Ca2+.

PMID- 7525893
TI  - Innervation and vasculature of human sweat glands: an immunohistochemistry-laser
      scanning confocal fluorescence microscopy study.
AB  - Secreting tubules, nerves fibers, and blood vessels in human sweat glands (SGs)
      were fluorescently stained by immunohistochemical and lectin methods for
      examination with a laser scanning confocal microscope (LSCM). Using these
      techniques, the three-dimensional distribution of up to three substances within a
      single specimen was investigated by collecting a series of optical sections for
      each of three fluorophores. Each SG received several nerve fibers. These branched
      into delicate bands of one or more axons that ran longitudinal to the sweat
      tubule then encircled the tubule. A heavy complement of capillaries was
      interwoven among the sweat tubules. Sweat ducts were accompanied from the SG
      toward the skin surface by one or two longitudinally oriented nerve fibers and
      capillaries. Immunoreactive staining of nerves was heaviest with protein gene
      product 9.5 antibody, but triple labeling showed that immunoreactivity to
      calcitonin gene-related peptide, vasoactive intestinal polypeptide, and
      synaptophysin was also present in the same axons. Substance P-immunoreactive
      axons were sparse in SGs but were present in other areas of the skin. The
      techniques used have considerable potential in examination of human skin biopsies
      for diagnosis of disorders affecting the somatic and autonomic nervous systems.

PMID- 7525894
TI  - Assembly of GABAA receptor subunits: role of the delta subunit.
AB  - GABAA receptor channels (GABARs) composed of different combinations of rat alpha
      1, beta 1, gamma 2L, and delta subunits were expressed transiently in mouse
      fibroblast cells (L929 cells). Whole-cell recordings were obtained from
      transfected cells to determine which combinations of GABAR subunits formed
      functional receptor channels, and to compare the electrophysiological and
      pharmacological characteristics of GABAR channels expressed in the presence and
      absence of the delta subunit. Only alpha 1 beta 1 gamma 2L, alpha 1 beta 1 gamma
      2L delta, and alpha 1 beta 1 delta subunit combinations assembled to form
      functional GABAR channels and the presence of the delta-subunit slowed the rate
      of acute desensitization of GABA-evoked current during GABA application and the
      rate of recovery of GABA-evoked current following GABA application. These three
      different GABAR channel isoforms also showed distinct pharmacological profiles
      with differential sensitivity to block by zinc. Zinc was a potent blocker of
      alpha 1 beta 1 delta GABAR channels, a moderate-strength blocker of alpha 1 beta
      1 gamma 2L delta GABAR channels, and did not block the alpha 1 beta 1 gamma 2L
      GABAR channels. These findings suggest that GABAR isoforms containing the delta
      subunit constitute a novel GABAR channel with distinct electrophysiological and
      pharmacological characteristics.

PMID- 7525895
TI  - Modulation of Ca2+ channels by PTX-sensitive G-proteins is blocked by N
      ethylmaleimide in rat sympathetic neurons.
AB  - The actions of N-ethylmaleimide (NEM), a sulfhydryl alkylating agent, on G
      protein-mediated inhibition of N-type Ca2+ channels in adult rat superior
      cervical ganglion (SCG) neurons were studied using whole-cell voltage clamp. In
      SCG neurons, inhibition of ICa occurs by at least three separable pathways: one
      pertussis toxin (PTX) sensitive and voltage dependent, and two PTX insensitive
      and voltage independent. NEM blocked PTX-sensitive inhibition nearly completely,
      with only small effects on PTX-insensitive inhibition. Somatostatin inhibition is
      completely PTX sensitive and was wholly blocked by a 120 sec exposure to 50
      microM NEM, with shorter exposure times producing a less complete block.
      Inhibition of ICa by norepinephrine (NE) is approximately half PTX sensitive and
      was also approximately half NEM sensitive. One component of muscarinic inhibition
      is PTX insensitive, voltage independent, and mediated by a diffusible cytoplasmic
      messenger; this pathway was largely spared by NEM treatment. Another pathway is
      also PTX insensitive and voltage independent, used by substance P, and was also
      largely NEM insensitive. Hence, in SCG neurons, NEM selectively inactivates PTX
      sensitive G-proteins. We also find evidence that the PTX-insensitive action of NE
      is distinct from the other PTX-insensitive pathways, and therefore assign it to a
      fourth signaling pathway.

PMID- 7525896
TI  - The L2/HNK-1 carbohydrate is preferentially expressed by previously motor axon
      associated Schwann cells in reinnervated peripheral nerves.
AB  - The carbohydrate epitope L2/HNK-1 (hereafter designated L2) is expressed in the
      adult mouse by myelinating Schwann cells of ventral roots and muscle nerves, but
      rarely by those of dorsal roots or cutaneous nerves. Since substrate-coated L2
      glycolipids promote outgrowth of cultured motor but not sensory neurons, L2 may
      thus influence the preferential reinnervation of muscle nerves by regenerating
      motor axons in vivo. In the present study, we have analyzed the influence of
      regenerating axons on L2 expression by reinnervated Schwann cells by directing
      motor or sensory axons into the muscle and cutaneous branches of femoral nerves
      of 8-week-old mice. We observed that regenerating axons from cutaneous branches
      did not lead to immunocytochemically detectable L2 expression in muscle or
      cutaneous nerve branches. Axons regenerating from muscle branches led to a weak
      L2 expression by few Schwann cells of the cutaneous branch, but provoked a strong
      L2 expression by many Schwann cells of the muscle branch. Myelinating Schwann
      cells previously associated with motor axons thus differed from previously
      sensory axon-associated myelinating Schwann cells in their ability to express L2
      when contacted by motor axons. This upregulation of L2 expression during critical
      stages of reinnervation may provide motor axons regenerating into the
      appropriate, muscle pathways with an advantage over those regenerating into the
      inappropriate, sensory pathways.

PMID- 7525897
TI  - The cAMP-dependent protein kinase regulates transcription of the dopamine beta
      hydroxylase gene.
AB  - Dopamine beta-hydroxylase (DBH) catalyzes the conversion of dopamine to
      norepinephrine, and is expressed specifically in neurons and neuroendocrine cells
      that release norepinephrine and epinephrine. In the present study, we used DBH
      expressing human neuroblastoma SK-N-BE(2)C and rat pheochromocytoma (PC12) cell
      lines to investigate the role of cAMP-dependent protein kinase (PKA) in
      transcriptional regulation of the DBH gene. Coexpression of the catalytic subunit
      of PKA (PKAc) robustly stimulated the transcriptional activity of the DBH gene in
      a dose-dependent manner. Conversely, coexpression of a specific inhibitor of PKA
      abrogated forskolin- and cAMP-mediated but not phorbol ester-mediated
      transcriptional induction of DBH. Deletion of the cAMP response element (CRE)
      dramatically reduced the stimulatory effect of PKA, indicating that the CRE
      mediates the induction of DBH by PKA. In DBH-nonexpressing HeLa and C6 glioma
      cell lines, coexpression of PKAc changed the transcriptional activity of the DBH
      promoter to a minimal degree, indicating that basal and PKA-mediated
      transcription of the DBH gene occur in a cell type-specific manner. Finally, both
      basal and cAMP-stimulated transcription of the DBH gene are diminished in three
      PKA-deficient PC12 cell lines, compared to wild-type cells. Based on these data,
      we conclude that PKA, via the CRE, plays an important role in basal and cAMP
      inducible transcription, but is not required for phorbol ester-mediated
      induction, of the DBH gene in noradrenergic cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7525899
TI  - Quantitative immunohistological analysis of the microvasculature in untreated
      human glioblastoma multiforme. Computer-assisted image analysis of whole-tumor
      sections.
AB  - Because histologically prominent microvascular proliferation is frequently
      present in glioblastoma multiforme, it has been hypothesized that this neoplasm
      is particularly dependent on neovascularization for its continued growth and that
      antiangiogenic therapy might be especially useful. To quantify the histological
      aspects of microvascular proliferation in glioma, a feasible and reproducible
      method was developed for computer-assisted image analysis of the visualized
      microvasculature in glial tissue. This method was used to compare several
      vascular parameters in histological whole-tumor sections of untreated human
      glioblastoma multiforme with those in histologically normal cerebral cortex and
      white matter. There was a significant increase in mean number, area, and
      perimeter of blood vessels per microscopic field in glioblastoma multiforme
      compared to normal cerebral white matter. In a substantial number of tumor
      fields, however, the vascular density was in the same range as that of normal
      cerebral white matter. The striking heterogeneity of the microvasculature within
      glioblastoma multiforme was illustrated by the significantly higher standard
      deviation for the vascular parameters in tumor tissue. The results of this study
      suggest that many regions of glioblastomas multiforme are not overtly
      angiogenesis dependent and may be difficult to treat by antiangiogenic therapy
      alone.

PMID- 7525888
TI  - Tumor invasion, proteolysis, and angiogenesis.
AB  - In this review, some of the current literature on the regulation of proteolysis
      and angiogenesis during tumor invasion is discussed. Due to the critical location
      of brain tumors, an understanding of tumor cell interactions with the local
      environment is particularly relevant. Tissue breakdown during tumor invasion is
      associated with proteolytic activity, mediated by tumor cells, and surrounding
      host cells. This review covers two classes of proteinases and inhibitors that
      have commonly been associated with tumor invasion i.e., plasminogen activator
      (PA)/plasmin and matrix metalloproteinases (MMP) with special emphasis on the MMP
      inhibitors, TIMP-1 and TIMP-2. At different steps of the metastatic process,
      tumor cells interact with endothelial cells. Tumor cells also stimulate the
      formation of new vessels through the expression of specific angiogenic molecules.
      At least eight angiogenic molecules have been purified, sequenced and cloned,
      four of which are discussed here. Regulation of angiogenic activity has been the
      focus of intense studies recently, and a wide range of synthetic and natural
      angiogenesis inhibitors have been discovered. Targeting of angiogenic molecules
      and tumor vasculature may prove useful in future cancer therapeutic strategies.

PMID- 7525898
TI  - Aluminum modifies the properties of Alzheimer's disease PHF tau proteins in vivo
      and in vitro.
AB  - Hyperphosphorylated adult human CNS tau (PHF tau or A68) forms paired helical
      filaments (PHFs) in neurofibrillary tangles (NFTs), neuropil threads, and
      dystrophic neurites associated with senile plaques (SPs) during the progression
      of Alzheimer's disease (AD). While amyloid fibrils in SPs are composed of beta
      amyloid (A beta), NFTs and SPs contain similar associated components such as
      ubiquitin, alpha 1-antichymotrypsin (ACT), apolipoprotein E (ApoE), heparan
      sulfate proteoglycans (HSPGs), and aluminum salts. Thus, SPs and NFTs may result
      from specific interactions between PHF tau, A beta, and these other components.
      In fact, intracerebral injections of PHF tau induce co-deposits of A beta, ACT,
      and ubiquitin (Shin et al., 1993). To examine this issue further, we probed
      interactions between PHF tau, aluminum salts, and other plaque and tangle
      components. We investigated in vivo interactions of PHF tau and aluminum chloride
      (AlCl3) with other plaque and tangle components by injecting PHF tau with and
      without AlCl3 into the rodent brain. PHF tau co-injected with AlCl3 formed
      aggregates that persisted much longer in the rat brain, and induced longer-lived
      co-deposits of A beta, ubiquitin, ACT, and ApoE than PHF tau alone. Injections of
      PHF tau with AlCl3 also induced neurons near the injection site to acquire PHF
      tau-like properties as monitored with antibodies (AT8, T3P, PHF1) that recognize
      defined PHF tau epitopes containing phosphoserine residues (Ser202, Ser396,
      Ser404). Injections of AlCl3 alone as well as injections of normal adult and
      fetal CNS tau, several different synthetic peptides, neurofilament proteins, ACT,
      HSPGs, or ApoE with and without AlCl3 failed to induce co-deposits of A beta or
      alter the immunoreactivity of tau in rodent neurons. To determine if aluminum
      salts interact directly and specifically with PHF tau in situ, we pretreated
      sections of AD hippocampus with 10 mM AlCl3 and then probed these sections by
      immunohistochemistry with antibodies to PHF tau as well as to a number of other
      plaque and tangle components. Preincubation of these sections with AlCl3
      diminished PHF tau immunoreactivity in NFTs and SPs using the PHF tau-specific
      antibodies AT8, T3P, and PHF1, while the immunoreactivity of other plaque and
      tangle proteins (A beta, ubiquitin, ACT, HSPGs, ApoE) was not abolished. We also
      examined the effects of AlCl3 on PHF tau and normal adult human CNS tau in vitro.
      AlCl3 had no effect on normal adult human CNS tau, while increasing
      concentrations of AlCl3 (from 0.1 to 1.0 mM) induced PHF tau to aggregate at the
      top of the stacking gel, and at high concentrations (0.3 and 1.0 mM) of AlCl3,
      PHF tau completely failed to enter the gel. These studies suggest that aluminum
      binds to PHF tau, induces these proteins to aggregate, and retards their
      proteolysis. Further, since intracerebral injections of PHF tau with and without
      AlCl3 in rats appear uniquely capable of inducing co-deposits of a number of
      proteins found in authentic AD SPs and NFTs (including A beta, ubiquitin, ACT,
      and ApoE), we speculate that the contributions of PHF tau to plaque and tangle
      formation in AD may be modulated by aluminum.

PMID- 7525900
TI  - Flare on bone scintigraphy following Taxol chemotherapy for metastatic breast
      cancer.
AB  - Our goal was to determine if a healing flare response seen on bone scintigraphy
      occurs following chemotherapy with Taxol (paclitaxel; Bristol-Myers Squibb Co.,
      Princeton, NJ), a novel antimicrotubule agent for metastatic breast cancer.
      METHODS: We performed 74 bone scans on 21 females with breast cancer and bone
      metastases entering a Phase II trial of Taxol chemotherapy with granulocyte
      colony stimulating factor (G-CSF). All patients had baseline scans within 6 wk
      prior to therapy, after the second cycle (4-6 wk) of Taxol, and then after 6-12
      mo. All bone scans were reviewed by two nuclear medicine physicians, without
      knowledge of the patients' clinical history. Skeletal radiographs, CT and MRI
      scans, as well as clinical history were compared with scan findings. RESULTS:
      Seven of the 21 patients showed improvement in bone scan findings. Of these
      seven, three had a flare response following two cycles (4-6 wk) of Taxol,
      characterized by increased activity in baseline lesions and the appearance of new
      lesions, followed by improvement on follow-up scans. Evidence of clinical
      response (> or = 50% reduction in tumor mass) was seen in all of these patients.
      Seven patients showed no change in baseline findings on follow-up bone scans.
      Seven patients had post-Taxol scans showing new lesions, with no overall
      improvement on later follow-up. CONCLUSION: Flare on bone scintigraphy may be
      seen shortly after commencing Taxol chemotherapy. Bone scans done within the
      first 3 mo must be interpreted with caution and should be correlated with
      clinical and radiological findings to avoid inappropriate discontinuation of
      Taxol chemotherapy.

PMID- 7525901
TI  - Randomized controlled trial for hepatocellular carcinoma with portal vein
      thrombosis: intra-arterial iodine-131-iodized oil versus medical support.
AB  - Portal vein thrombosis is a poor prognostic factor in patients with
      hepatocellular carcinoma (HCC) and a contraindication for chemoembolization.
      Intra-arterial injection of 131I-iodized oil which does not modify arterial flow,
      is feasible in this condition. The aim of this prospective randomized controlled
      trial was to compare the efficacy of treatment with radiolabeled oil (treated
      group) versus medical support (control group) in patients with stage I or II HCC
      (classification of Okuda) with portal vein thrombosis. METHODS: Twenty-seven HCC
      patients (26 males, 1 female), aged 53-79 yr, with portal vein thrombosis were
      randomly assigned to Lipiocis group (n = 14) or Control group (n = 13).
      Additional injections of radiolabeled oil were given 2, 5, 8 and 12 mo after
      initial therapy. Medical support treatment consisted of: tamoxifen (n = 5), 5 FU
      intravenously (n = 1), NSAIDs or corticosteroids (n = 5). Efficacy was evaluated
      according to survival rate (Kaplan-Meier method; log rank test), AFP serum values
      (measured at 2, 5, 8 and 12 mo) and angiography. RESULTS: The two groups were
      comparable (Child's classification, Okuda's classification, liver function tests,
      location of the thrombus). Tolerance was excellent in the Treated group. The
      actuarial survival curves were significantly different (p < 0.01) between the two
      groups, the survival rates (Cl 95%) at 3, 6 and 9 mo being 71% (48%-95%), 48%
      (12%-55%), 7% (1%-31%) for the Treated group; and 10% (1%-33%), 0% and 0% for the
      Control group. CONCLUSION: Intra-arterial hepatic injection of 131I-labeled
      iodized oil is a safe and effective palliative treatment of HCC with portal vein
      thrombosis.

PMID- 7525902
TI  - Predictive value of the Bayley mental scale in the early detection of cognitive
      delays in high-risk infants.
AB  - One of the most elusive developmental disabilities to diagnose during infancy is
      cognitive delay. Although infant intelligence tests have been identified
      repeatedly as poor predictors of future IQ, these predictions have typically been
      based on interage correlations. This retrospective study examined the
      sensitivity, specificity, and positive and negative predictive values of the
      Mental Scale of the Bayley Scales of Infant Development in detecting cognitive
      delay (IQ < 85) among a sample of 196 high-risk, mostly low birth weight,
      premature infants who were assessed initially at 4 months' corrected age and
      followed longitudinally to between 3 and 8 years' corrected age. As hypothesized,
      the Bayley Mental Scale was better at correctly identifying children with future
      normal IQs (specificity = 91.9%) than it was at identifying infants who would
      later show cognitive delays (sensitivity = 38.9%). The positive and negative
      predictive values were 51.9% and 87.0% respectively. Results of this study
      support recent assertions that cognitive delay, particularly in the mildest
      forms, is difficult to detect during early infancy.

PMID- 7525904
TI  - Developmental disabilities: genetic implications.
AB  - Knowledge and new techniques in genetics can aid in a better understanding of
      developmental disabilities. Through new treatments and better assessment skills,
      individuals with disorders such as phenylketonuria (PKU), Down syndrome, and
      fragile X syndrome are having diagnoses sooner and are living into adulthood.
      With the passage of public law 99.457, early intervention services are mandated
      for those who are 3 years old or younger and are developmentally delayed or at
      risk for delay. Organizations for paraprofessionals and professionals in the
      arena of developmental disabilities and genetics exist to create a forum for
      future action, awareness, and direction.

PMID- 7525905
TI  - Palliative, intraarterial chemotherapy for advanced head and neck cancer using an
      implantable port system.
AB  - PURPOSE: Intraarterial drug therapy for head and neck cancer has been used for
      more than 30 years. However, because of catheter-related complications occurring
      quite frequently, this method was abandoned in many institutions. The development
      of subcutaneously implantable injection ports has renewed interest in regional
      drug delivery. PATIENTS AND METHODS: This study reports the authors' experience
      with 11 injection ports implanted in 10 patients suffering from advanced or
      recurrent head and neck cancer. RESULTS: The regional chemotherapy was well
      tolerated; the predominant side effects were hemialopecia and mild unilateral
      mucositis. CONCLUSIONS: These results suggest that regional, intra-arterial
      chemotherapy using implantable injection ports should be considered for
      palliative treatment of advanced head and neck cancer.

PMID- 7525906
TI  - Long-term results of blood flow and cutaneous sensibility of flaps used for the
      reconstruction of facial soft tissues.
AB  - PURPOSE: The aim of this study was to determine the blood flow and the cutaneous
      sensibility of flaps after the repair of tumor-related defects of the facial
      skin. PATIENTS AND METHODS: Fifty restorations (27 local flaps, 6 island flaps, 7
      free skin grafts, and 10 microvascular grafts) were examined using laser Doppler
      flowmetry, two-point discrimination, and a pain and thermal sensibility testing
      device. The average postoperative interval was 62 months. Measurements were
      performed on the flap surface, the donor site, and the contralateral areas
      corresponding to the donor site and the former defect. Paired t-tests were used
      to assess statistically significant differences between the sites of measurement.
      RESULTS: Results showed a rate of both blood flow and two-point discrimination on
      the surface of local flaps and island flaps that was not statistically different
      from the corresponding area of the unoperated side. Free skin grafts exhibited
      incomplete restoration of thermal sensibility and increased blood flow rates
      compared with the donor site. Large microvascular flaps showed complete loss of
      cutaneous sensibility in six cases, whereas partial restitution without
      reproducible two-point discrimination was found in the remaining patients after
      an average interval of 39 months. Flowmetry rates of microvascular flaps
      corresponded to those of the donor site and were significantly lower than those
      of the recipient site in the head and neck area.

PMID- 7525907
TI  - CD3: structure, function, and role of immunostaining in clinical practice.

PMID- 7525908
TI  - Dermal vascularity in lentigo maligna.
AB  - Lentigo maligna (LM) may represent a tumour arrested in an in situ phase, lacking
      the angiogenic capacity and underlying dermal neovascularization required for
      invasive growth. The acquisition of an angiogenic phenotype might be associated
      with the development of lentigo maligna melanoma (LMM). To investigate this
      thesis, sections of formalin-fixed, paraffin-embedded tissue from 15 LMMs, and 11
      LM excision specimens were stained with the vascular endothelial marker Ulex
      europaeus agglutinin I. Dermal vessels were counted and vascular morphometry was
      performed. In specimens in which LMM was present, dermal vascularity was
      significantly increased in LM compared with normal skin. The most significant
      increases were found for dermal vascular density (39 per cent increase, P =
      0.008) and for total vessel surface area (62 per cent increase, P = 0.005).
      However, when no LMM was present, the vascular density underlying LM (79 +/- 9
      vessels/mm2) did not differ significantly from that of adjacent normal skin (67
      +/- 6 vessels/mm2), although focal 'hot spots' of increased vascularity were
      present. We conclude that increased dermal vascularity is present beneath in situ
      LM and that this increased vascular density is closely associated with the
      presence of invasive LMM in the same specimen.

PMID- 7525903
TI  - Prostate cancer, screening, and prostate-specific antigen: promise or peril?

PMID- 7525909
TI  - Site of production of IGF1 in the normal and stimulated mouse thyroid.
AB  - Insulin-like growth factor 1 (IGF1) has emerged as an essential factor in the
      follicular cell growth response in vitro to TSH, although its source within the
      thyroid in vivo is not clear. We have studied the localisation of IGF1 mRNA by in
      situ hybridization using digoxigenin labelled oligoprobes in tissue sections of
      mouse thyroid. Our results show that in the thyroid IGF1 mRNA is predominantly
      present in follicular cells and C cells rather than the stroma. Follicular cell
      levels are higher during postnatal thyroid growth and during the growth response
      to goitrogen administration, but decrease in the mature animal. This decrease in
      production is limited to the follicular cells, as IGF1 mRNA is still easily
      demonstrable in C cells and in the parathyroid. Immunocytochemistry for IGF1
      peptide shows a weak and variable follicular cell content in both juvenile and
      mature mice, but a more uniform distribution during growth in response to a
      goitrogenic stimulus. These studies show that the follicular cells are the main
      source of IGF1 in the thyroid, and suggest that the role of IGF1 in follicular
      cell growth is as an autocrine factor.

PMID- 7525911
TI  - Assessment of epidermal dendritic cell markers and T-lymphocytes in psoriasis.
AB  - Epidermal dendritic and T-cell counts have been performed in lesional and non
      lesional skin from 35 psoriatic patients. The aims were to investigate absolute
      changes and interrelationships between these cellular elements in psoriasis and
      to explain apparent discrepancies between these results and reports in the
      literature. In non-lesional skin, the most frequently expressed dendritic cell
      marker was CD1a. HLA-DR+ and alpha-mannosidase+ dendritic cells were
      approximately 50 per cent and S100+ cells were 25 per cent as frequent. T
      lymphocytes were rare, CD4+ cells predominating. In lesional psoriatic epidermis,
      there was a definite increase (approximately two-fold) in the absolute number of
      CD1a+ dendritic cells. This differs from the conclusions from the majority of
      previous studies. However, when cell counts were expressed per unit area of
      vertical section, there was a decrease in CD1a+ cells in lesional skin, which is
      an explanation for this discrepancy. There was a greater increase in absolute HLA
      DR+ cell counts, so that the numbers of cells expressing CD1a and HLA-DR were
      similar in lesional skin. S100 expression increased proportionately with CD1a+,
      but there was no absolute increase in alpha-mannosidase+ cells, which might
      represent a separate sub-population of dendritic cells. The greatest cellular
      increase was in T-lymphocytes, particularly CD8+. In lesional skin, direct
      correlations have been demonstrated between epidermal thickness, HLA-DR+
      dendritic cells and T-lymphocytes, particularly CD8+ cells. We would suggest that
      the present method of quantification is of value for the analysis of absolute
      changes in epidermal infiltrates, particularly psoriasis, and could be applied to
      other epidermal pathologies.

PMID- 7525910
TI  - Decreased expression of cellular markers in Epstein-Barr virus-positive Hodgkin's
      disease.
AB  - Epstein-Barr virus (EBV) has been demonstrated in the Reed-Sternberg cells and
      their mononuclear variants (Hodgkin cells; H-RS cells) in a substantial number of
      Hodgkin's disease (HD) cases. Moreover, EBV can modulate both in vivo and in
      vitro the expression of several cellular genes, including lymphoid
      differentiation markers. Therefore we investigated, in 64 cases of HD, the
      relationship between the presence of EBV and the expression of lymphoid (CD45RB),
      T- (CD3, CD45RO), B- (CD20, MB2 antigen, CDw75), and myeloid-cell lineage markers
      (CD15), and of activation markers (CD30, EMA, and the 115D8 antigen) on the H-RS
      cells. EBV-positive cases, as demonstrated by the presence of EBER-1 and -2 RNA
      and LMP-1 protein expression, showed a significant reduction in the expression on
      H-RS cells of T-cell lineage (CD3, P < 0.02), B-cell lineage (CD20; P < 0.005),
      and activation markers (EMA; P < 0.002 and the 115D8 antigen; P < 0.001) as
      compared with EBV-negative cases. No differences were found in the expression of
      CD15, CD30, CD45RO, CD45RB, CDw75, or the MB2 antigen on H-RS cells in EBV
      positive and EBV-negative HD cases. Interestingly, in 11 cases of EBV-negative
      HD, B- as well as T-cell lineage markers could be found on some H-RS cells. These
      data suggest that EBV in H-RS cells is able to down-regulate the expression of T-
      (CD3) and B- (CD20) cell lineage markers and lymphoid activation markers (EMA and
      the 115D8 antigen).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525912
TI  - Expression of integrins and CD44 isoforms in non-Hodgkin's lymphomas: CD44
      variant isoforms are preferentially expressed in high-grade malignant lymphomas.
AB  - Low- and high-grade malignant non-Hodgkin's lymphomas have been investigated by
      immunohistochemistry for their expression of various integrins and CD44 isoforms.
      Comparison with the expression patterns obtained in non-malignant adult lymph
      nodes revealed the following differences: alpha 6 and beta 4 integrins were
      expressed in several high-grade malignant lymphomas to a lower degree than in
      both the low-grade malignant lymphomas and the normal lymph nodes; all other
      integrins (alpha 2, alpha 4, alpha 5, alpha v, beta 1, beta 2, beta 3, and beta
      7) did not exhibit significant differences in the expression levels between
      malignant and non-malignant tissues. The standard isoform of CD44 (CD44s) was
      highly expressed in all lymphoid tissues. Using CD44 exons-specific monoclonal
      antibodies, CD44 variant isoforms were not detected in non-malignant lymph nodes
      and were detected only rarely in low-grade malignant lymphomas. In contrast, high
      grade malignant lymphomas expressed several CD44 variant isoforms, which included
      the products from the variant exons 3v, 6v, and 9v, but not 4v. Specifically,
      detection of exon 3v and 6v products indicates a more aggressive phenotype.

PMID- 7525913
TI  - Long-term outcome in children with opsoclonus-myoclonus and ataxia and coincident
      neuroblastoma.
AB  - We reviewed the neurologic and developmental courses in 10 children with
      opsoclonus-myoclonus ("dancing eyes syndrome") and neuroblastoma. All patients
      are alive without evidence of neoplastic disease after 8+ to 111+ months of
      follow-up. All had localized disease and 50% had extraabdominal tumors.
      Neuroblastomas of nine children had favorable Shimada histologic characteristics,
      and all tumors had single copies of the N-myc oncogene. After neuroblastoma
      resection, all patients had persistent opsoclonus-myoclonus or ataxia that
      responded to therapy with adrenocorticotropic hormone. Nine children had relapses
      of neurologic symptoms. Three years after resection, six of seven patients with
      sufficient follow-up were free of symptoms and had discontinued therapy. However,
      nine children had chronic neurologic deficits, including cognitive and motor
      delays, language deficits, and behavioral abnormalities. All six patients in
      educational programs required special assistance. Five children required
      physical, occupational, or speech therapy. Long-term developmental and cognitive
      problems should be anticipated in patients with neuroblastoma who have opsoclonus
      myoclonus or ataxia or both, and early intervention should be instituted to try
      to minimize these deficits.

PMID- 7525915
TI  - Development of children born after ovarian superovulation induced by long-acting
      gonadotropin-releasing hormone agonist and menotropins, and by in vitro
      fertilization.
AB  - The use of a gonodotropin-releasing hormone (Gn-RH) agonist in an in vitro
      fertilization (IVF) program raises the question of any influence on the physical,
      neurologic, and mental development of the children. We compared the development
      of children born after long-acting Gn-RH agonist treatment with that of children
      born after spontaneous pregnancies. Children from singleton pregnancies and > or
      = 28 months of age were examined by a pediatric neurologist and a psychologist
      who did not know to which group the children belonged. The General Cognitive
      Index test was used. Each group included 30 children. Five children cooperated
      only partly. Physical and neurologic findings were normal in all children, except
      that one in the group born after in vitro fertilization had diffuse hypotonia,
      attention-deficit hyperactivity disorder, and hyperactivity. The General
      Cognitive Index for the 26 children in the study group and the 29 children in the
      control group who fully cooperated were 102 +/- 13.3 and 106 +/- 13.5,
      respectively (p = 0.37). The verbal perception, motor, and memory indexes were
      not significantly different. We conclude that the long-acting Gn-RH agonist had
      no clinically identifiable influence on the development of these children.

PMID- 7525914
TI  - Successful in vivo immunolocalization of Langerhans cell histiocytosis with use
      of a monoclonal antibody, NA1/34.
AB  - The antibody NA1/34 is a murine monoclonal antibody directed against the CD1a
      surface antigen expressed on normal Langerhans cells, cortical thymocytes, and on
      lesional cells in Langerhans cell histiocytosis (LCH). Our hypothesis was that
      NA1/34 would localize sites of disease activity in patients with multisystem LCH.
      To test this hypothesis, indium 111-labeled NA1/34 was administered to five
      patients with multisystem LCH and serial gamma scans were obtained for up to 120
      hours. Serial serum samples were obtained from one patient for analysis of anti
      mouse Ig antibody and NA1/34 levels. Direct and indirect immunofluorescence
      staining for CD1a and NA1/34 were performed on a tissue biopsy specimen from one
      patient after administration of the antibody. The 1- and 4-hour scans showed
      distribution of antibody in the blood pool, but in later scans localization of
      the antibody was noted in areas of known disease activity in all five patients.
      Bony lesions, previously seen on skeletal radiographs, were especially well
      identified. Serum kinetics studies showed clearance of the antibody from the
      blood pool within 12 hours of administration. Direct binding of NA1/34 to
      lesional cells was demonstrated by direct immunofluorescence. The only adverse
      effect was urticaria in one patient. We conclude that NA1/34 localizes disease
      activity in vivo in bones of patients with LCH with minimal toxic effects. An
      evaluation of its role in determining disease extent ("staging") and in treatment
      is now needed.

PMID- 7525916
TI  - The 16S-like, 5.8S and 23S-like rRNAs of the two varieties of Cryptococcus
      neoformans: sequence, secondary structure, phylogenetic analysis and restriction
      fragment polymorphisms.
AB  - The nucleotide sequences of the 16S-like, 5.8S and 23S-like rDNAs from the two
      varieties of Cryptococcus neoformans, C. neoformans var. neoformans and C.
      neoformans var. gattii, were determined. The rRNA locus has the typical eukaryote
      organization of 16S-5.8S-23S with the 16S-like and 5.8S rRNA genes separated by a
      124-nucleotide spacer and the 5.8S and 23S-like rRNA genes separated by a 187
      nucleotide spacer in each strain. The C. neoformans var. neoformans and C.
      neoformans var. gattii 16S-like, 5.8S and 23S-like rRNAs are, respectively 1802,
      158, and 3358 nucleotides in length and share > 99% nucleotide sequence identity,
      a finding which strongly supports the present taxonomic classification of two
      varieties within a species. Comparative structure analysis was used to construct
      secondary-structure models for the deduced 16S-like and 5.8S-23S-like rRNA
      sequences, which are similar to those of other fungal rRNAs. The C. neoformans
      16S-like and 23S-like rRNA sequences were aligned with other eukaryote sequences
      based on secondary and higher-order structures predicted by comparative structure
      analysis for phylogenetic analysis. There was good correspondence between the 16S
      like and 23S-like derived phylogenetic trees. The closest known fungal relative
      is Trichosporon beigelii. Southern blot analysis revealed one C. neoformans
      strain with two types of DNA repeats coding for rRNA which differed in size by
      about 1000 bp. Restriction fragment length polymorphisms in the rDNA locus
      provide useful markers for the study of epidemiology and pathogenesis of C.
      neoformans infections.

PMID- 7525919
TI  - Childhood independence: views of Cuban and Haitian immigrant mothers.
AB  - Failure of nurses and other health care providers to recognize the influence of
      culture on child development may lead to inappropriate expectations and
      mislabeling of children as developmentally slow. The effect of cultural
      influences on parental expectations of children was evident in a study of child
      rearing beliefs of 30 Cuban and 30 Haitian immigrant mothers in South Florida.
      Both Cuban and Haitian children would be considered lagging developmentally when
      compared with measurements on the personal-social dimension of the Denver II and
      expectations of American society. Culture-specific implications for transcultural
      nursing care based on the concept of culture brokerage are discussed.

PMID- 7525920
TI  - Diabetes-induction reduction in the hepatic accumulation of 70-kDA dextran: role
      of hyperglycemia and hypoinsulinemia.
AB  - In vivo studies were conducted in rats to determine the role of hyperglycemia and
      hypoinsulinemia in the previously reported reduction in the hepatic accumulation
      and increase in the serum concentrations of 70-kDa fluorescein-dextran (FD-70) in
      diabetic (D) rats. The serum, urine, and hepatic concentrations of FD-70 were
      measured by size exclusion chromatography after i.v. administration of a single
      doses (5 mg/kg) of FD-70. Intravenous administration of a single 2 IU/kg dose of
      insulin to D rats at time zero or 4 h after the administration of FD-70 resulted
      in an increase in some and no change in other animals in their rate of
      elimination of FD-70 from serum. The presence or absence of a significant insulin
      effect on the disposition of FD-70 in these animals was, respectively, associated
      with the presence or absence of a significant insulin-induced hypoglycemic
      effect. Fasting D rats for 24 h caused normoglycemia, and subsequently, the
      disposition of FD-70 became similar to that in nondiabetic (ND) rats. Likewise,
      i.p. injections of glucose to ND rats rendered them hyperglycemic, and the
      disposition of FD-70 in these rats became similar to that in untreated D animals.
      However, i.v. injection of glucose, which did not result in sustained
      hyperglycemia, did not change the disposition of FD-70 in ND rats. Further, the
      disposition of FD-70 remained unaffected by an i.v. 2 IU/kg dose of insulin
      administered to ND rats at time zero. Considering all animals, there was a
      significant negative relationship between the 12-h hepatic recovery of FD-70 and
      the area under the serum concentration-time curves of glucose. It is concluded
      that the reduction in the hepatic accumulation of FD-70 in D rats is due to
      hyperglycemia and not

PMID- 7525918
TI  - Redistribution of organ blood flow after hemorrhage and resuscitation in full
      term piglets.
AB  - Newborn piglets (aged 1 to 2 days and 7 to 14 days) were used to study (1) the
      redistribution of organ blood flow after a 25% acute blood loss and (2) the
      response to resuscitation with shed blood (20 mL/kg), crystalloid (normal saline
      [NS] or lactated Ringer's [LR]; 60 mL/kg), and colloid (Dextran-40, 20 mL/kg).
      Hemodynamic parameters showed little differences in the response to hemorrhage
      and resuscitation. The two age groups had no significant differences in
      parameters or blood flow (results combined). The animals maintained flow to the
      heart and central nervous system (CNS) and had significantly decreased flow to
      the kidneys and splanchnic organs. In the gastrointestinal tract, the small
      intestine was affected most severely, with a significant decrease in blood flow,
      especially to the mucosa. In all organ systems, Dextran 40 restored blood flow to
      levels significantly above the baseline. Shed blood and crystalloid restored flow
      to organs sustaining decreased flow, but crystalloid did not restore flow to the
      baseline level in the kidney and all segments of the gastrointestinal tract.

PMID- 7525921
TI  - Estimation and correlation of drug water solubility with pharmacological
      parameters required for biological activity.
AB  - A procedure for estimating the molar water solubility (S) for a series of
      structurally related drug compounds is presented. HPLC methods for the
      determination of partition coefficients (P) are combined with semiempirical
      calculations for S. Multidimensional plots are developed with the physical
      constants S and P along the x and y axes and with a biological response, e.g.
      IC50 or ED50, along the z axis. Other attributes, e.g. bioavailability or
      biodistribution, can be added by color coding, shading, or numbering. Since the
      methods have a high throughput capability, parameters governing the events
      leading to pharmacological action [i.e. gastrointestinal dissolution (S),
      absorption (P), blood level (bioavailability), and biological action (IC50,
      EC50)] can be correlated for drug series comprising large numbers of compounds.

PMID- 7525917
TI  - Biology of fetal wound healing: hyaluronate receptor expression in fetal
      fibroblasts.
AB  - Fetal tissue repair is rapid, relatively scarless, and proceeds in an environment
      rich in hyaluronic acid. Understanding the interaction of hyaluronic acid (HA)
      with the reparative cells may provide important insight into the remarkable
      process of fetal wound healing. Therefore, the purpose of this study was to
      characterize the HA receptor (a member of the CD44 family of cell surface
      glycoproteins) and its density on the cell surface of fetal fibroblasts. HA
      receptor expression on both adult and fetal fibroblasts was first studied by
      Western blot analysis. Autoradiographs of the blots were assessed by densitometry
      to quantitate the relative amounts of the HA receptor. It appears that the HA
      receptor expressed on both adult and fetal rabbit dermal fibroblasts is a 56-kd
      protein. After normalizing for total protein concentration using the Bradford
      protein assay, the fetal HA receptor density was found to be approximately four
      fold greater than that of the adult. The same adult and fetal fibroblasts were
      then studied by flow cytometry, using a fluorescence-activated cell sorter
      (FACS). Relative fluorescence was representative of HA receptor density.
      Corroborating the authors' earlier result with the Western blot analysis, the
      FACS analysis showed that the fetal fibroblasts had 2.5 times the fluorescence of
      the adult cells. It is concluded that, in comparison to adult fibroblasts, fetal
      fibroblasts have an increased density of cell-surface HA receptor.

PMID- 7525922
TI  - In the search for new anticancer drugs. 26. A comparison of anticancer activities
      of several TEPA, thio-TEPA, Seleno-TEPA, and azetidine analogs, including
      congeners containing an aminoxyl moiety.
AB  - A series of TEPA, Thio-TEPA, Seleno-TEPA, and azetidine analogs, including
      congeners containing an aminoxyl moiety, were synthesized and evaluated in vivo
      for anticancer activity against the murine lymphocytic leukemia P388. All
      aziridine derivatives were found to be active with an increase in life span
      ranging from 42% to 272%, and all azetidine analogs were rated as inactive with
      one marginal exception. An attempt was made to rationalize the results on the
      basis of the lipophilic properties of the compounds. The most active compound (8)
      possessed the most balanced lipophilic properties, corresponding to a log P value
      near zero.

PMID- 7525923
TI  - Humanized monoclonal antibody DREG-200 directed against I-selectin protects in
      feline myocardial reperfusion injury.
AB  - Polymorphonuclear leukocytes (i.e. neutrophils) significantly mediate damage in
      myocardial ischemia followed by reperfusion. In the present study, the
      cardioprotective effects of a humanized form of a monoclonal antibody directed
      against L-selectin designated monoclonal antibody (mAb) HuDREG-200 were examined
      in a feline model of 90-min myocardial ischemia followed by 270 min of
      reperfusion. In preliminary studies, flow cytometric analysis indicated that
      HuDREG-200 binds to feline neutrophils. In vitro administration of mAb HuDREG-200
      significantly inhibited (P < .01) adherence of unstimulated neutrophils to
      ischemic-reperfused coronary endothelium in a concentration-dependent manner.
      Humanized DREG-200 (2 mg/kg) administered 10 min before reperfusion significantly
      attenuated myocardial necrosis compared to an isotype-matched humanized control
      mAb (HuABL364) which does not bind to L-selectin (14 +/- 3 vs. 29 +/- 3%
      necrosis/area-at-risk, P < .01), representing a 52% reduction in myocardial
      necrosis. This myocardial preservation also was related to reduced creatine
      kinase release and improved recovery of cardiac contractility (i.e. left
      ventricular dP/dtmax). Moreover, endothelial function, as assessed by relaxation
      to acetylcholine, also was significantly preserved in ischemic-reperfused
      coronary arteries isolated from cats treated with mAb HuDREG-200 compared to mAb
      HuABL364 (68 +/- 6 vs. 18 +/- 5, P < .01). Thus, a humanized anti-L-selectin mAb
      appears to be an effective means of preserving the ischemic myocardium from
      reperfusion injury and of preserving myocardial contractile function, at least
      during the early reperfusion period.

PMID- 7525924
TI  - Non-N-methyl-D-aspartate receptor antagonism by 3-N-substituted 2,3
      benzodiazepines: relationship to anticonvulsant activity.
AB  - Block of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) and kainate
      currents by GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8- methylenedioxy-5H-2,3
      benzodiazepine], a noncompetitive non-N-methyl-D-aspartate (AMPA/kainate)
      receptor antagonist, and two 3-N-substituted 3,4-reduced GYKI 52466 analogs was
      assessed in whole cell voltage-clamp recordings from cultured rat hippocampal
      neurons. In addition, the activity of the analogs was determined in the maximal
      electroshock seizure test and for protection against kainate-induced seizures in
      mice. The analogs of GYKI 52466 tested were the 3-N-methylcarbamyl [GYKI 53655; 1
      (4-aminophenyl)-3-methylcarbamyl-4- methyl-3,4-dihydro-7,8-methylenedioxy-5H-2,3
      benzodiazepine] and the 3-N-acetyl [GYKI 53405; 1-(4-aminophenyl)-3-acetyl-4
      methyl-3,4-dihydro-7,8-methylenedioxy-5H-2, 3- benzodiazepine]. GYKI 53655
      produced a concentration-dependent inhibition of AMPA- and kainate-induced
      currents with IC50 values of 1.1 and 1.5 microM, respectively; the corresponding
      values for GYKI 53405 were 3.8 and 5.0 microM. As blockers of AMPA currents, the
      analogs were 8- and 2.3-fold, respectively, more potent than the parent GYKI
      52466. Kinetic analyses indicated increased association rates for the two 3-N
      substituted analogs (2.5-2.6 x 10(5) M-1 sec-1) compared with GYKI 52466 (1.6 x
      10(5) M-1 sec-1). The dissociation rates of GYKI 52466, GYKI 53405 and GYKI 53655
      were inversely correlated with increasing blocking potency (2.9, 1.7 and 0.6 sec
      1, respectively). Thus, the increased affinity of the 3-N-substituted analogs
      relates to their increased binding and decreased unbinding rates.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7525925
TI  - NK1 receptors mediated release of 6-keto-PGF1 alpha from the ex vivo perfused
      canine ileum.
AB  - The purpose of this study was to determine the effects of tachykinins on
      prostanoid production by the dog ileum and to characterize the tachykinin
      receptor(s) responsible for the principal eicosanoid shown to be released, 6-keto
      PGF1 alpha. Substance P, the selective NK1 receptor agonist
      [Sar9,Met(O2)11]substance P and neurokinin A caused concentration-dependent
      production of 6-keto-PGF1 alpha; neurokinin A was least potent. The selective NK2
      agonist [Nle10]neurokinin A(4-10) had no effect. The selective NK1 antagonist CP
      96,345 (10(-7) M), blocked 6-keto-PGF1 alpha release from substance P (10(-7) M),
      [Sar9,Met(O2)11]substance P (10(-7) M) and neurokinin A (10(-7) M). Although the
      putative NK2 antagonist MEN 10207 (10(-7) M) partially blocked the 6-keto-PGF1
      alpha release induced by neurokinin A (10(-7) M), we conclude that all these
      peptides acted primarily on NK1 receptors to induce 6-keto-PGF1 alpha. Additional
      experiments suggest that a major site of production of 6-keto-PGF1 alpha in the
      canine ileum may be the vasculature, but these experiments do not exclude other
      sources such as intestinal muscle for this prostanoid. Calcium-free Krebs'
      solution partially reduced the release of 6-keto-PGF1 alpha to substance P (10(
      7) M), implying that extracellular calcium helps support tachykinin-induced
      production of 6-keto-PGF1 alpha. Blockade of synthesis of another vasoactive
      mediator, endothelium-derived relaxing factor (nitric oxide), by N omega-L
      arginine methyl ester) did not alter substance P-induced release of 6-keto-PGF1
      alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525927
TI  - Induction of heart heme oxygenase-1 (HSP32) by hyperthermia: possible role in
      stress-mediated elevation of cyclic 3':5'-guanosine monophosphate.
AB  - Presently we have investigated the carbon monoxide generating capacity of the
      cardiovascular system under normal and stress conditions by examining the
      microsomal heme oxygenase system at the transcript, protein and activity levels;
      and have assessed response of heart nitric oxide (NO) synthase activity and
      cyclic GMP levels to stress. Heme oxygenase (HO) isozymes, HO-1 (HSP32) and HO-2,
      catalyze the rate limiting step in the only known pathway in eukaryotes for the
      generation of the potential cellular message, carbon monoxide, and the
      antioxidant, bilirubin. We show expression of HO-1 and HO-2 at both the
      transcription and protein levels under normal conditions in the heart and
      descending aorta, and demonstrate the sensitivity of only the HO-1 isozyme to
      heat stress in these tissues. The ratio of the two HO-2 homologous transcripts
      (approximately 1.9 and 1.3 Kb) present in the atrium, ventricles and descending
      aorta and their levels were not altered by hyperthermia (42 degrees C, 20 min)
      when measured 1 or 6 hr after treatment. In contrast, hyperthermia caused a
      rapid, robust and coordinate increase of approximately 10- to 32-fold in the
      approximately 1.8-Kb HO-1 mRNA in these tissues when measured 1-hr post
      treatment. Hyperthermia also caused a significant increase in both HO-1 protein
      and heme degradation capacity in the heart. Furthermore, the induction of HO-1
      protein in the heart was accompanied by a significant elevation in tissue cyclic
      GMP level first detected 1-hr post-treatment and was sustained 6 hr after heat
      shock.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525926
TI  - Beta-adrenergic regulation of gap-junctional intercellular communication in
      cultured rabbit gastric epithelial cells.
AB  - The effect of a beta-adrenergic agonist, isoproterenol, on gap-junctional
      intercellular communication (GJIC) and intracellular cyclic AMP (cAMP) content
      was investigated in cultured rabbit gastric epithelial cells. Isoproterenol
      rapidly enhanced GJIC determined by the Lucifer yellow transfer at 10(-6) and 10(
      5) M but the effect at 10(-6) M was variable. The enhancement of GJIC by 10(-5) M
      isoproterenol, which disappeared within 10 or 30 min, was inhibited by a beta
      blocker, propranolol. Isoproterenol (10(-6) M) greatly increased cAMP at 5 min
      and much more so at 20 min after its addition. Colforsin (also known as
      forskolin) and 3-isobutyl-1-methylxanthine (IBMX) enhanced GJIC until 16 and 20
      min after their addition, respectively. Both colforsin and IBMX increased the
      cAMP content by a lesser extent than 10(-6) M isoproterenol. Isoproterenol (10(
      5) M) inhibited the GJIC enhanced by colforsin or IBMX. Propranolol abolished the
      inhibition of GJIC by isoproterenol in the presence of IBMX. Both amiloride, an
      inhibitor of the Na+/H+ exchanger, and nigericin, a K+/H+ antiporter, inhibited
      the GJIC enhanced by isoproterenol, IBMX, colforsin and irsogladine. An inhibitor
      of cAMP-dependent protein kinase A, H-89 (N-[2-((3-(4- bromophenyl)-2-propenyl)
      amino)-ethyl]-5-isoquinolinesulfonamide), abolished the enhancement of GJIC by
      colforsin and IBMX but did not abolish that by isoproterenol.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7525928
TI  - Effects of prostacyclin analogs on the synthesis of tissue factor, tumor necrosis
      factor-alpha and interleukin-1 beta in human monocytic THP-1 cells.
AB  - Previous studies have shown that prostacyclin analogs can inhibit the expression
      of tissue factor (TF) procoagulant activity by human monocytes. The present
      studies have investigated this phenomenon further, by using a plasma coagulation
      assay to measure cellular TF activity, an immunoassay to measure TF antigen and
      reverse transcription/polymerase chain reaction with appropriate oligomer primers
      to measure TF mRNA. Iloprost and cicaprost inhibited lipopolysaccharide-induced
      increases in TF activity, antigen and mRNA (50% inhibition, 2-8 nM), with no
      apparent effect on TF mRNA stability. These agents therefore act at or before the
      level of transcription of the TF gene. The analogs were more potent inhibitors of
      tumor necrosis factor-alpha synthesis (50% inhibition at 334 +/- 40 pM cicaprost
      or 846 +/- 182 pM iloprost) and extraordinarily potent when combined with a
      phosphodiesterase inhibitor (50% inhibition at 101 +/- 31 pM iloprost in the
      presence of 20 microM isobutylmethylxanthine). Iloprost and cicaprost were less
      potent in inhibiting the synthesis of interleukin-1 beta (50% inhibition, 50-100
      nM). Cicaprost inhibited lipopolysaccharide-induced increases in mRNA levels for
      TF, tumor necrosis factor-alpha and interleukin-1 beta; differential potency was
      again observed. We conclude that these three important monocyte functions can be
      down-regulated by prostacyclin analogs, and with differential sensitivity.
      Furthermore, the extreme sensitivity of tumor necrosis factor-alpha synthesis to
      inhibition suggests that such inhibition may be a major physiological function of
      prostacyclin itself.

PMID- 7525929
TI  - Drug discrimination assessment of agonist-antagonist opioids in humans: a three
      choice saline-hydromorphone-butorphanol procedure.
AB  - To assess the discriminative stimulus properties of mixed agonist-antagonist
      opioids in humans, postaddict volunteers were trained in a three-choice drug
      discrimination procedure to discriminate among the effects of saline (4 ml i.m.),
      hydromorphone (3 mg i.m.) and butorphanol (6 mg i.m.). Subjects earned monetary
      reinforcement by correctly identifying the training drugs by letter code. Other
      subjective, behavioral and physiological measures were concurrently collected.
      After training, generalization curves for hydromorphone, butorphanol,
      pentazocine, nalbuphine and buprenorphine were determined. In generalization
      testing, both hydromorphone and butorphanol produced dose-related increases in
      hydromorphone-appropriate and butorphanol-appropriate responses, respectively,
      and other characteristic subjective effect measures. Nalbuphine produced dose
      related increases in discrimination as butorphanol and in those subjective effect
      measures increased by butorphanol. Buprenorphine produced dose-related increases
      in discrimination as hydromorphone and in those subjective effect measures
      increased by hydromorphone. Pentazocine was not consistently discriminated as
      either butorphanol or hydromorphone. These results differ from those of previous
      discrimination studies using similar methods but different training drugs.
      Compared to a previous study in which pentazocine served as the kappa-like
      training drug, the use as a training drug of the more pharmacologically specific
      kappa-like drug butorphanol permitted greater differentiation among test drugs
      and yielded discrimination results more consistent with other pharmacological
      evidence (buprenorphine being mu-like and nalbuphine being kappa-like). There was
      a close relationship between results of the discrimination measures and the
      subjective effect measures.

PMID- 7525930
TI  - Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. II.
      The rundown and inward rectification of agonist-elicited whole-cell currents and
      identification of receptor subunits by in situ hybridization.
AB  - Our previous study demonstrated for the first time that nicotinic currents evoked
      in rat hippocampal neurons could be grouped into four categories (types IA, IB,
      II and III) according to their functional and pharmacological characteristics. In
      the second part of our continuing studies, the structural and functional
      diversity of nicotinic receptors expressed in hippocampal neurons was further
      explored. Type IA, the predominant and alpha-bungarotoxin-sensitive current, but
      not type II, the alpha-bungarotoxin-insensitive current, showed rundown in the
      peak amplitude during the whole-cell recording. The rundown of type IA currents
      could be prevented when the ATP-regenerating compound phosphocreatine, alone or
      in combination with ATP and creatine phosphokinase, was added to the internal
      recording solution. The addition to the internal solution of either the
      microfilament-stabilizing agent phalloidin (5 microM) or the microtubule
      stabilizing agent taxol (50 microM) did not alter or prevent rundown in type IA
      currents. Type IA and type II currents showed inward rectification. The inward
      rectification of type IA currents was dependent on the presence of intracellular
      Mg++, whereas that of type II currents was independent of Mg++. When Mg++ was
      present in the internal pipette solution, the inward rectification of type IA
      currents was sustained throughout the recording time. However, when nominally
      Mg(++)-free internal solution was used, the inward rectification decreased with
      recording time in type IA currents, but not in type II currents, as a consequence
      of removal of intracellular Mg++. In situ hybridization demonstrated the presence
      of alpha 7-, alpha 4- and beta 2-nicotinic acetylcholine receptor subunit mRNAs
      in cultured hippocampal neurons. The distribution among the neurons of the mRNAs
      for alpha 7- and alpha 4-nicotinic acetylcholine receptor subunits, correlated
      with the frequency with which type IA and type II currents, respectively, could
      be evoked in these neurons. The present results provide evidence for 1) the
      presence of intracellular high-energy phosphate-dependent processes linked with
      the nicotinic acetylcholine receptor subserving type IA currents, 2) a
      requirement of intracellular Mg++ for the inward rectification of type IA
      currents and 3) a correlation between the distribution of nAChR subunits and the
      different probabilities of eliciting distinct types of nicotinic currents in
      hippocampal neurons.

PMID- 7525932
TI  - Magnesium and zinc potentiate ethanol inhibition of N-methyl-D-aspartate
      stimulated nitric oxide synthase in cortical neurons.
AB  - The coupling of calcium mobilizing receptors to nitric oxide (NO) formation was
      examined in cerebral cortical cultures. Of the various agents tested, only
      glutamate, depolarization with KCl and the calcium ionophore ionomycin stimulated
      nitric oxide synthase (NOS) activity. Characterization of the glutamate response
      revealed that the ionotropic glutamate receptor agonists N-methyl-D-aspartate
      (NMDA), kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic all
      stimulated NOS activity with a relative maximal efficacy of NMDA > kainate >
      alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic. Ethanol, Mg++ and Zn++
      produced a concentration-dependent inhibition of NMDA stimulation of NOS. The
      Mg++ inhibition was reversed by increasing concentrations of NMDA, whereas Zn++
      inhibition was not. Ethanol (100 mM) produced an apparent competitive type
      inhibition as seen by a parallel right-shift in the NMDA concentration-response
      curve. However, ethanol inhibition was dependent upon the presence of Mg++ and/or
      Zn++ in a concentration-related manner. Whereas 100 mM ethanol did not
      significantly inhibit NMDA stimulation of NOS activity in the absence of Mg++ and
      Zn++, inclusion of a combination of these cations increased the sensitivity to
      ethanol such that the NMDA response was completely blocked by 100 mM ethanol
      (IC50 approximately 30 mM). The potency for inhibition of NMDA stimulation of NOS
      by several short-chain alcohols followed their hydrophobicity profile and showed
      a similar dependency upon Mg++ for inhibition, alpha-amino-3-hydroxy-5-methyl-4
      isoxalone propionic, but not kainate, stimulation of NOS was also inhibited by
      ethanol (100 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7525933
TI  - Substance P activates rat colonic motility via excitatory and inhibitory neural
      pathways and direct action on muscles.
AB  - We studied effects of nicotinic, muscarinic, serotoninergic, dopaminergic,
      adrenergic, vasoactive intestinal peptide (VIP) antagonists, VIP, nitric oxide
      synthase inhibitors and stimulators alone and in combination with tetrodotoxin on
      substance P (SP)-stimulated intraluminal tone of the isolated proximal, middle
      and distal rat colon. Tetrodotoxin significantly enhanced SP-stimulated
      intraluminal tonic pressure in the distal, but not in the middle and proximal
      colon. N omega-nitro-L-arginine methylester enhanced SP stimulation in all
      colonic segments, whereas L-arginine inhibited it partially and D-arginine did
      not affect it. Atropine and hexamethonium partially inhibited SP stimulation of
      the middle and distal colon. Tetrodotoxin completely abolished the effects of L
      arginine, atropine and/or hexamethonium on SP stimulation. Propranolol,
      phentolamine, reserpine, telenzepine, naloxone, Mr 2266, a VIP antagonist (H9935)
      and ketanserin did not affect SP-induced colonic muscle stimulation. VIP strongly
      reduced SP-stimulated intraluminal pressure in all colonic segments. VIP(10-28),
      a putative VIP antagonist, produced similar inhibition of SP-stimulated
      intraluminal tonic pressure, but did not affect N omega-nitro-L-arginine
      methylester-induced enhancement of SP-stimulated intraluminal pressure in any
      segments. It is concluded that in the isolated rat colon SP-stimulated
      intraluminal pressure (mainly generated by circular muscles) by a direct action
      on colonic muscles over the whole colonic length and by simultaneous activation
      of neural cholinergic excitatory pathways in the middle and distal, of
      noncholinergic excitatory pathways in the proximal colonic segment, and by
      activation of nitric oxide-dependent inhibitory neural pathways. VIP seems not to
      be directly involved in this inhibitory pathway.

PMID- 7525934
TI  - A diaminoantraquinone inhibitor of angiogenesis.
AB  - Tumor growth is dependent upon angiogenesis. There is an intense search for
      pharmacological inhibitors of angiogenesis as a novel approach to treat
      angiogenic diseases, e.g., arthritis, diabetic retinopathy or cancer. A series of
      compounds, originally studied as potential protein kinase C inhibitors, included
      the diaminoanthraquinone NSC 639366 (1-[[3-(diethylamino)-2-hydroxypropyl]amino]
      4-[(2,3- epoxypropyl)amino]-9,10-anthracenedione fumaric acid salt) (SPC-100097),
      was found to reversibly inhibit bovine endothelial cell growth with an IC50 that
      ranged between 1 and 4 nM. NSC 639366 reversibly inhibited endothelial cell
      migration, particularly endothelial cells stimulated by the potent angiogenic
      molecule, basic fibroblast growth factor. The activity of secreted urokinase-type
      plasminogen activator and active interstitial collagenase, but not gelatinase,
      was inhibited by NSC 639366. In vivo, angiogenesis was significantly inhibited by
      NSC 639366 by using the chick chorioallantoic membrane or the rat corneal
      bioassay. Two analogs of NSC 639366 did not inhibit endothelial cell growth.
      These experiments introduce a novel compound that could be clinically useful
      against angiogenic diseases and encourage further development of compounds that
      inhibit the plasminogen-plasmin system known to be a key regulator of
      angiogenesis.

PMID- 7525931
TI  - Induction of 12-lipoxygenase expression by epidermal growth factor is mediated by
      protein kinase C in A431 cells.
AB  - Epidermal growth factor (EGF) increases 12-lipoxygenase mRNA by about 2-fold with
      a lag period of 4 to 8 hr, which precedes the increase in 12-lipoxygenase
      activity by 2 to 4 hr in human epidermoid carcinoma A431 cells. Induction of 12
      lipoxygenase expression in human erythroleukemia cells by phorbol 12-myristate 13
      acetate (PMA) has been reported previously. The present report describes a study
      of the involvement of protein kinase C (PKC) in EGF-induced 12-lipoxygenase
      expression in A431 cells. EGF-induced 12-lipoxygenase expression was inhibited by
      methyl 2,5-dihydroxycinnamate, a tyrosine kinase inhibitor. Staurosporine and
      calphostin C, which are two PKC inhibitors, inhibited EGF-induced enzyme activity
      and mRNA expression of 12-lipoxygenase. 1,2-Dioctanoyl-sn-glycerol (a membrane
      permeant diacylglycerol) and PMA significantly induced enzyme activity and mRNA
      expression. Simultaneous treatment of cells with EGF and PMA did not exhibit an
      additive effect, suggesting that EGF and PMA share a common biochemical pathway
      in 12-lipoxygenase induction. Expression of mRNA for PKC alpha, delta and zeta
      was detected in A431 cells, whereas no mRNA expression for PKC beta 1, gamma and
      epsilon was observed. Taken together, these results suggest that EGF-induced 12
      lipoxygenase expression is at least in part mediated by the PKC signal
      transduction pathway.

PMID- 7525935
TI  - Strychnine-binding proteins in intestinal cells: novel brucine binding site with
      binding affinities for alkaloids.
AB  - The purpose of this work was to define the pharmacology of an intestinal
      epithelial [3H]strychnine binding site. Strychnine, brucine, verapamil and
      desmethoxyverapamil bind to small intestinal mucosal homogenates with nanomolar
      affinity at a site not related to the strychnine receptor, which is in the spinal
      cord. The antidiarrheal agents, fluperamide and loperamide, and several alkaloids
      have an order of magnitude lower affinity. Agents that bind to cytochrome
      P450IID6 also displace [3H]strychnine binding, which implies that the binding
      site may have some properties similar to the catalytic site of this cytochrome
      P450 enzyme.

PMID- 7525936
TI  - In vitro neuroprotection by substituted guanidines with varying affinities for
      the N-methyl-D-aspartate receptor ionophore and for sigma sites.
AB  - Radioligand binding techniques were used to determine the affinity of a series of
      substituted guanidine derivatives for 1) the binding site within the ion channel
      of the N-methyl-D-aspartate (NMDA) receptor, as defined by displacement of MK-801
      ([3H]dizocilpine) and 2) sigma sites as defined by displacement of [3H]N,N'-di-(o
      tolyl)guanidine. The goal was to find ligands with high affinity and selectivity
      for the NMDA receptor ion-channel site. The neuroprotective activity of these
      compounds was assessed by their ability to protect cortical neurons from injury
      caused by a 5-min exposure to 500 microM glutamate in vitro. Release of lactate
      dehydrogenase into the culture medium by damaged neurons was used as an index of
      neuronal injury. The 14 compounds tested had IC50 values ranging from 37.3 nM to
      12.7 microM for the NMDA receptor ion-channel site and from 8.3 nM to 7.25 microM
      for sigma sites. Affinity for the ion-channel site was improved by unsymmetrical
      substitutions on the guanidine moiety. All compounds in the series protected
      cortical neurons against glutamate toxicity, with EC50 values (concentration
      affording 50% protection) ranging from 0.38 to 28.25 microM. The neuroprotective
      effect of each compound was positively correlated with its ion-channel site
      affinity (r = 0.94); no correlation between neuroprotective efficacy and sigma
      site binding affinity was found (r V -0.13) establishing clearly that
      neuroprotection in this assay was linked to NMDA antagonist properties.

PMID- 7525937
TI  - Effects of nitric oxide synthase inhibition on the pathophysiology observed in a
      model of chronic granulomatous colitis.
AB  - The objective of this study was to assess the role that nitric oxide (NO) may
      play in mediating the colonic inflammation observed in a model of chronic
      granulomatous colitis using two pharmacologically different inhibitors of nitric
      oxide synthase (NOS). The NOS inhibitors NG-nitro-L-arginine methyl ester (L
      NAME; 15 mumol/kg/day) and aminoguanidine (AG; 15 mumol/kg/day) were administered
      to rats in their drinking water, beginning 3 days before the induction of colitis
      and continuing for the entire 3-week period. We found that chronic NOS inhibition
      by L-NAME or AG significantly attenuated the peptidoglycan/polysacchride (PG/PS)
      induced increases in macroscopic colonic inflammation scores and colonic MPO
      activity. Only AG, and not L-NAME, attenuated the PG/PS-induced increases in
      colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced
      increases in spleen inflammation, whereas neither drug significantly attenuated
      the PG/PS-induced liver inflammation. Although both L-NAME and AG inhibited NO
      production in vivo, as measured by decreases in plasma nitrite and nitrate
      levels, only AG was found to attenuate these values significantly (38 +/- 3 vs.
      83 +/- 8 microM, respectively; P < .05). Finally, administration of L-NAME, but
      not of AG, significantly increased mean arterial pressure from 83 mm Hg in
      colitic animals to 105 mm Hg in the PG/PS+L-NAME-treated animals (P < .05). We
      conclude that NO may play an important role in mediating some of the
      pathophysiology associated with this model of chronic granulomatous colitis.

PMID- 7525939
TI  - Interleukin-1 beta inhibits synaptic transmission and induces membrane
      hyperpolarization in amygdala neurons.
AB  - Interleukin-1 beta (IL-1 beta), a mediator of immune response, is found in the
      brain and IL-1 binding sites are located in the basolateral amygdala (BLA).
      Superfusion of IL-1 beta (118 pM) hyperpolarized the membrane and decreased input
      resistance in most BLA neurons in brain slice preparations. The hyperpolarization
      was dose dependent, reversible, persisted in tetrodotoxin and had an estimated
      EC50 of 15.3 pM. Reversal potentials for the hyperpolarization recorded with
      potassium acetate and KCl electrodes were -74 and -40 mV, respectively. These
      data suggest involvement of a chloride conductance. The hyperpolarization was not
      observed in bicuculline or in acutely dissociated BLA neurons, which implicates
      an indirect mediation through enhancement of endogenous gamma-aminobutyric acid
      (GABA). Superfusion of IL-1 beta (118 pM) inhibited excitatory and fast and slow
      inhibitory postsynaptic potentials evoked by stimulating either the stria
      terminalis or the lateral amygdala. Fast and slow inhibitory postsynaptic
      potentials elicited by direct stimulation of GABA interneurons in the lateral
      amygdala were also depressed by IL-1 beta. IL-1 beta did not depress responses to
      GABA or glutamate receptor agonists in slices or currents induced by glutamate
      agonists in acutely dissociated BLA neurons. These findings indicate that
      inhibition of synaptic transmission is presynaptic. The results show that IL-1
      beta inhibits excitatory and inhibitory transmission at a presynaptic site and
      hyperpolarizes the membrane through an indirect action, possibly by enhancing the
      action of endogenous GABA in the BLA nucleus. The inhibitory effect of IL-1 beta
      suggests that factors in the immune system play a role in modulating neuronal
      function in the BLA.

PMID- 7525938
TI  - Regulation of the responses to gonadotropin-releasing hormone, muscarine and
      substance P in sympathetic neurons by changes in cellular constituents and
      intracellular application of peptide fragments of the substance P receptor.
AB  - The effects of alterations of intracellular constituents on the actions of three
      agonists [gonadotropin-releasing hormone, muscarine and substance P (SP)] on the
      M-type potassium current in bullfrog sympathetic neurons were examined.
      Application of maximal concentrations of each agonist resulted in inhibition of M
      current followed by desensitization. Desensitization was greatest during SP
      application, less with gonadotropin-releasing hormone and least after muscarine.
      Recovery after agonist washout was greatest for SP, less for muscarine and least
      for gonadotropin-releasing hormone. The effects of varying intrapipette pH,
      [ATP], Ca buffer and free Ca on inhibition by each of the agonists,
      desensitization and recovery were tested. Comparison of the effects of different
      intracellular constituents showed that desensitization and recovery are distinct
      phenomena. Desensitization was greatest with 3 mM ATP in the pipette and was
      enhanced when pyruvate and glucose were added extracellularly. Two synthetic
      peptides, comprising amino acids 325-360 and 361-375, respectively, of the
      carboxyl tail of the rat SP receptor inhibited desensitization to SP, but not to
      the other agonists. A third peptide homologous to residues 376-407 and a peptide
      from the extracellular portion of the receptor (residues 168-179) did not affect
      desensitization. This suggests that the portion of the carboxyl tail of the SP
      receptor from amino acids 325-375 is involved in desensitization.

PMID- 7525941
TI  - Effect of potassium channel blockers on relaxations to a nitric oxide donor and
      to nonadrenergic nerve stimulation in guinea pig trachea.
AB  - Nonadrenergic, noncholinergic (NANC) relaxations were elicited by field
      stimulation (1-16 Hz, 1 msec, 12 V for 15 sec) of guinea pig trachea desensitized
      with capsaicin (3 microM); pretreated with atropine (1 microM), propranolol (1
      microM), indomethacin (3 microM) and alpha-chymotrypsin (2 U/ml) and contracted
      with 3 microM histamine. The nitric oxide (NO) synthase inhibitor L-nitro-N
      arginine (L-NNA) significantly inhibited these responses, which is indicative of
      NO involvement. The ability of the large conductance Ca(++)-activated K+ channel
      antagonists iberiotoxin (IbTx) and charybdotoxin (ChTx) and the small conductance
      Ca(++)-activated K+ channel antagonist apamin to modify relaxations to NANC nerve
      stimulation and to the NO donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1)
      was studied. Both IbTx (100 nM) and ChTx (100 nM) were found to inhibit the L-NNA
      sensitive relaxations elicited by field stimulation and to inhibit the
      relaxations to SIN-1. In contrast, apamin did not inhibit the relaxations to
      either field stimulation or SIN-1. These results suggest that in the guinea pig
      trachea, responses to endogenous or exogenously added NO are at least in part
      mediated by the large conductance Ca(++)-activated K+ channel.

PMID- 7525940
TI  - Inhibition of nitric oxide synthase delays gastric emptying of solid meals.
AB  - The role of nitric oxide (NO) was investigated in the regulation of gastric
      emptying of solid meals in six conscious dogs. N omega-nitro-L-arginine methyl
      ester (L-NAME), an inhibitor of NO synthase, significantly delayed gastric
      emptying. L-Arginine, the substrate of NO, given alone also significantly delayed
      gastric emptying compared with that in the saline control group but the delay
      with this chemical was significantly less than that with L-NAME. L-Arginine given
      with L-NAME significantly shortened the delay in gastric emptying caused by L
      NAME. The delay in gastric emptying after the administration of L-NAME was
      primarily due to selective stimulation of the frequency of pyloric and proximal
      duodenal contractions without a concurrent change in antropyloroduodenal
      coordination. The delay in gastric emptying by L-arginine was primarily due to
      the suppression of gastric contractions. L-Arginine given with L-NAME completely
      reversed the motor effects of L-NAME. It was concluded that NO is a physiologic
      neurotransmitter of nonadrenergic, noncholinergic neurons in the stomach, pylorus
      and the duodenum that acts to regulate gastric emptying of solid meals. NO may
      facilitate gastric emptying by partially inhibiting pyloric and proximal duodenal
      contractions.

PMID- 7525942
TI  - Sulphorhodamine-labelled cells in the neonatal rat spinal cord following
      chemically induced locomotor activity in vitro.
AB  - 1. Sulphorhodamine 101, a fluorescent dye and newly identified activity marker,
      was used to localize potential spinal locomotor networks in the neonatal rat
      spinal cord. 2. Preparations of the spinal cord with one entire hindlimb attached
      or the spinal cord in isolation were kept in vitro. Spinal locomotor activity was
      maintained chemically with NMDA (5-7.5 microM), in combination with 5-HT (7.5-20
      microM), for 4-4.5 h in the presence of 0.0001-0.0005% sulphorhodamine 101.
      Matched non-locomoting controls were exposed to the dye in the absence of
      transmitters for a comparable time. Transverse sections of the lumbar spinal cord
      (L1-L6) were screened for rhodamine emission using an epifluorescence microscope.
      3. In hindlimb-attached locomoting preparations with intact dorsal roots,
      labelled cells were found on the leg side in the dorsal horn (mainly laminae II
      IV), in the intermediate grey (lamina VI-VII) and around the central canal
      (lamina X). Dorsal rhizotomy was performed on the leg side, to prevent synaptic
      activity due to afferent inflow. This largely reduced the number of labelled
      cells in the dorsal horn and in the lateral part of the intermediate grey matter.
      A further reduction of labelling in these areas was seen after complete isolation
      of the cord or when compared to the legless side, with the majority of labelled
      cells persisting in a bilateral cluster close to the central canal and in the
      medial intermediate grey. Few labelled cells were observed in non-locomoting
      preparations. The intensity of motoneuronal labelling was variable.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7525943
TI  - A rise in the intracellular Ca2+ concentration of isolated rat supraoptic cells
      in response to oxytocin.
AB  - 1. Intracellular Ca2+ concentration ([Ca2+]i) was monitored in single cells
      isolated from adult rat supraoptic (SO) nuclei. The great majority of cells (85%)
      were neurones and most were immunoreactive to oxytocin or to vasopressin (AVP).
      2. The resting [Ca2+]i of the majority (80%) of the neurones remained stable
      while 20% of the neurones displayed spontaneous [Ca2+]i oscillations which
      disappeared in low-Ca2+ (100 nM) EGTA buffer. 3. Addition of 100 nM oxytocin
      increased the [Ca2+]i in both stable and oscillating cells. Two types of
      responses were observed: (i) a sustained response with [Ca2+]i being maintained
      at an elevated level and (ii) a brief response with [Ca2+]i quickly returning to
      a near-resting level. Responses were reproducible, dose dependent and blocked
      with a specific oxytocin antagonist. 4. Removal of extracellular Ca2+ did not
      block the oxytocin response. In EGTA buffer, application of thapsigargin (200 nM)
      onto oxytocin-sensitive cells induced an increase in [Ca2+]i and inhibited the
      oxytocin response. These effects were not induced by other intracellular Ca2+
      mobilizers such as tBuBHQ (see Methods) or caffeine. 5. In conclusion, half of
      the SO cells respond to oxytocin with a rise in [Ca2+]i. The effect is mediated
      by oxytocin receptors and results from release of Ca2+ from thapsigargin
      sensitive stores.

PMID- 7525945
TI  - Simultaneous expression of cardiac and skeletal muscle isoforms of the L-type
      Ca2+ channel in a rat heart muscle cell line.
AB  - 1. We have investigated the identity of the L-type Ca2+ channels present in the
      H9c2 myoblast line derived from embryonic rat ventricle. To this end, we
      characterized macroscopic and unitary Ba2+ currents through Ca2+ channels, and
      looked for specific genetic messages encoding different L-type Ca2+ channel
      isoforms. 2. The macroscopic Ba2+ current (recorded in 10 mM BaCl2) revealed two
      components with different time courses of activation. The fast component
      (IBa,fast) activates with a time constant of 23 +/- 12 ms (at +10 mV), while the
      slow component activates with a time constant of 125 +/- 12 ms (at +10 mV). 3.
      Single-channel recordings revealed the presence of two independent channels with
      conductance values of 11 and 25 pS (in 70 mM Ba2+). These values are identical to
      those reported previously for skeletal muscle and cardiac Ca2+ channels,
      respectively. 4. The mean ensemble current from the 11 pS channel reproduced the
      time course of the slow component observed at the macroscopic level, while the 25
      pS ensemble time course paralleled that of the fast component. 5. Reverse
      transcriptase polymerase chain reaction (PCR) with alpha 1-isoform-specific
      primers revealed the presence of two distinct transcripts in H9c2 cells. The
      sequences of the PCR products showed a high degree of homology with the
      corresponding segments of the rabbit cardiac and skeletal muscle L-type Ca2+
      channel isoforms. Adult rat skeletal and cardiac muscle expressed only one type
      of transcript. 6. H9c2 cells appear to be unique in that they simultaneously
      express both skeletal muscle and cardiac isoforms of the L-type Ca2+ channel
      alpha 1-subunit. Thus, the H9c2 cell line may prove to be useful when studying
      the regulation of subtype-specific Ca2+ channel gene expression.

PMID- 7525946
TI  - Endogenous H+ modulation of NMDA receptor-mediated EPSCs revealed by carbonic
      anhydrase inhibition in rat hippocampus.
AB  - 1. The occurrence of extracellular alkaline transients during excitatory synaptic
      transmission suggests that the NMDA receptor H(+)-modulatory site may have a
      physiological role. Here we amplify these pH shifts using benzolamide (a carbonic
      anhydrase inhibitor) and describe concomitant effects on EPSCs in whole-cell
      clamped CA1 neurones in rat hippocampal slices. 2. In CO2-HCO3(-)-buffered media,
      benzolamide increased the time to 50% decay (t50) of the EPSCs by 78 +/- 14% (P <
      0.01, n = 10). This occurred simultaneously with amplification of the
      extracellular alkaline shift (154 +/- 14%). 3. In CO2-HCO3(-)-buffered media
      containing DL-2-amino-5-phosphonovalerate (APV), the EPSC t50 was unaltered by
      benzolamide, while the extracellular alkaline shifts were increased (111 +/- 23%,
      n = 8). 4. In Hepes-buffered media, neither the EPSC t50 nor the extracellular
      alkaline shift was altered by benzolamide (n = 9). 5. These data demonstrate that
      NMDA receptor activity is dependent on the buffering kinetics of the brain
      extracellular space. The results suggest that endogenous pH shifts can modulate
      NMDA receptor function in a physiologically relevant time frame.

PMID- 7525944
TI  - Effect of metabolic inhibitors and second messengers upon Na(+)-H+ exchange in
      the sheep cardiac Purkinje fibre.
AB  - 1. Acid extrusion through Na(+)-H+ exchange was studied in the sheep cardiac
      Purkinje fibre (bathed in Hepes-buffered solution, nominally free of CO2-HCO3-)
      by examining (i) intracellular pH (pHi) recovery from an intracellular acid load
      (induced by 20 mM NH4Cl prepulse) and (ii) the rate of rise of intracellular Na+
      activity (aiNa) following the ammonium prepulse (used as an estimate of apparent
      Na+ influx on Na(+)-H+ exchange). The pHi and aiNa were recorded using ion
      selective microelectrodes. 2. The pHi recovery and rise of aiNa were both greatly
      slowed in the presence of 2-deoxyglucose (DOG; glucose-free solution), an
      inhibitor of glycolysis, indicating inhibition of Na(+)-H+ exchange. 3. Cyanide
      moderately slowed pHi recovery rate but did not significantly affect the rise of
      aiNa. Estimates of beta 1 (intracellular buffering power) indicated an increase
      of approximately 50% in the presence of cyanide; such an increase accounts for
      most of the observed slowing of pHi recovery. It is concluded that oxidative
      inhibition with cyanide does not inhibit Na(+)-H+ exchange. 4. Intracellular ATP,
      measured from luciferin-luciferase luminescence, was reduced by a similar amount
      (approximately 70%) by either DOG or cyanide. This suggests that, if
      intracellular ATP (ATPi) reduction is the cause of exchanger inhibition by
      metabolic inhibitors, then ATPi generated glycolytically is more important for
      activation of the exchange. 5. 3-Isobutyl-1-methylxanthine (IBMX; a non-specific
      phosphodiesterase inhibitor which can elevate intracellular [cAMP]) slowed acid
      extrusion and reduced apparent Na+ influx by a similar amount, whereas addition
      of sodium nitroprusside (to elevate intracellular [cGMP]) had no effect,
      suggesting that raising intracellular [cAMP] downregulates Na(+)-H+ exchange,
      whereas raising intracellular [cGMP] does not. 6. Application of trifluorperazine
      (TFP; a non-specific calcium-calmodulin inhibitor) completely reversed the
      inhibitory effects of IBMX upon pHi recovery and aiNa. Under control conditions
      (no IBMX), TFP had no effect on pHi recovery or upon resting pHi. 7. The phorbol
      ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) had no significant effect on
      pHi recovery or apparent Na+ efflux. 8. We conclude that inhibition of glycolysis
      or elevation of cAMP produces downregulation of Na(+)-H+ exchange in the cardiac
      Purkinje fibre. Possible reasons for the lack of inhibitory effect of oxidative
      inhibitors are discussed.

PMID- 7525947
TI  - Alpha 1-adrenoceptors in rat dorsal raphe neurons: regulation of two potassium
      conductances.
AB  - 1. alpha 1-Adrenoceptor activation caused two separate effects in rat dorsal
      raphe neurons: a depolarization and an increase in the duration of the after
      hyperpolarization following the action potential. The depolarization often
      resulted in repetitive action potentials. The alpha 1-adrenoceptor antagonists
      prazosin and WB 4101 blocked the depolarization induced by phenylephrine. The
      concentration-response curve to phenylephrine was shifted to the right by WB
      4101. 2. Under voltage clamp, alpha 1-adrenoceptor agonists caused an inward
      current at -60 mV, which often became smaller at negative potentials but rarely
      reversed polarity even at strongly negative potentials. Using whole-cell
      recording, the inward current reversed polarity at the equilibrium potential for
      potassium in the majority of cells. Intracellular Cs+ decreased or abolished the
      alpha 1-mediated inward current. The inward current was dependent on external
      calcium, but not on the degree of internal calcium buffering. Removal of external
      calcium or addition of MgCl2, CoCl2 or CdCl2 reduced or blocked the effects of
      alpha 1-adrenoceptor agonists. Barium and strontium supported and even augmented
      the inward current induced by alpha 1-adrenoceptor agonists, whereas nifedipine
      and omega-conous toxin had no effect. In contrast, internal dialysis with the
      calcium chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA)
      did not inhibit the inward current. 3. The alpha 1-induced depolarization was
      blocked (or occluded) by the inclusion of GTP-gamma-S (100 microM) in the
      recording pipette. The phorbol-ester 4-phorbol 12,13-dibutyrate (PDBu) had no
      action on the membrane potential and depressed the phenylephrine-induced
      depolarization. This depression was reversed by the non-selective protein kinase
      inhibitor staurosporin. 4. Phenylephrine and noradrenaline increased a late
      component of the after-hyperpolarization (late-AHP) that followed a single action
      potential. The alpha 1-sensitive late-AHP was blocked by apamine suggesting that
      it is a calcium-dependent potassium conductance. 5. Thapsigargin reduced the
      duration of the late-AHP and blocked the phenylephrine-mediated prolongation.
      Caffeine also augmented the late-AHP and ryanodine blocked the augmentation
      induced by caffeine. The augmentation induced by phenylephrine was not occluded
      by caffeine and was still present after the caffeine-induced augmentation was
      blocked by ryanodine. 6. In slices pretreated with manoalide the depolarization
      induced by alpha 1-agonists was not changed; however, the late-AHP was reduced in
      duration and the alpha 1-receptor-mediated augmentation of the late-AHP was
      decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525948
TI  - Swelling-induced anion and cation conductances in human epididymal cells.
AB  - 1. Activation of both anion and cation conductances was observed in primary
      cultured human epididymal cells during osmotic swelling under the patch-clamp
      whole-cell configuration. The swelling-induced anion conductance was 25.66 +/-
      4.70 nS and the cation conductance was 7.35 +/- 1.40 nS. The permeability ratio
      of K+ to Cl- (PK/PCl) was calculated to be 0.40. Known anion or cation channel
      blockers could inhibit both conductances simultaneously. 2. When the major
      permeant ion species in the pipette and bath solution was Cl-, the mean
      conductance was found to be 17.06 +/- 1.8 nS, significantly smaller than that
      obtained in the presence of intracellular K+, 25.66 +/- 4.70 nS (P < 0.05). No
      significant current activation was observed when solutions containing only K+ as
      the permeant ion were used. 3. When the anionic amino acids glutamate and
      aspartate were used to replace extracellular Cl-, the permeability ratios were
      calculated to be PGlut/PCl = 0.20 and PAsp/PCl = 0.17. 4. The cation conductance
      was found to be non-selective since its permeability to other cations such as Na+
      and choline, an organic compound highly concentrated in epididymal fluid, was
      similar to that of K+. 5. Regulatory volume decrease (RVD) was observed after
      initial osmotic swelling; this could be inhibited by either anion or cation
      channel blockers. 6. The results of this study suggest that both anion and cation
      conductances are activated during cellular swelling, and indicate the existence
      of an interdependent relationship between the swelling-induced cation and anion
      conductances. Both swelling-induced cation and anion conductances are involved in
      the volume regulatory process and may be responsible for transporting amino acids
      or organic compounds in human epididymal cells.

PMID- 7525950
TI  - Biological and morphological characteristics of a transplanted cartilaginous
      tumor derived from a human osteogenic sarcoma.
AB  - A cartilaginous tumor derived from a human osteogenic sarcoma of the mandible has
      been maintained by serial passage to nude mice. Tumor growth was multilobular.
      Radiopaque spots were seen scattered throughout the tumor at three months after
      transplantation. Both light and electron microscopic examination at three months
      revealed that the tumor contained cartilaginous cells at various stages of
      differentiation. There was metachromasia throughout tumor lobules except in the
      marginal region. Von Kossa staining was positive in the central region.
      Ultrastructural study identified four subtypes of chondrocytic cells of a
      neoplastic nature. In the extracellular matrix around hypertrophic cells, matrix
      vesicles were observed with mineral deposits. Alkaline phosphatase was found on
      the plasma membrane and Golgi complexes of hypertrophic cells, and on matrix
      vesicles. Thus cell lineage and the manner of calcification of the transplanted
      tumor were similar to those of epiphyseal growth cartilage.

PMID- 7525951
TI  - Storytelling: using an ancient art to work with groups.
AB  - 1. Storytelling can be used to reduce social isolation and lack of connection. 2.
      Group storytelling, in which group members create a story together, has
      therapeutic value in the psychiatric milieu. 3. The experienced therapist/nurse
      therapist is the best person to conduct a storytelling group in the psychiatric
      setting.

PMID- 7525949
TI  - Flash photolysis studies of the localization of calcium release sites in rat
      parotid isolated acinar cells.
AB  - 1. The temporal relationship between cytosolic free Ca2+ concentration ([Ca2+]i)
      and activation of membrane current responses in single rat parotid acinar cells
      has been examined. Activation of muscarinic receptors by carbachol (CCh) at -40
      mV (midway between EK and ECl under our experimental conditions) frequently
      evoked biphasic current responses, application of 2 microM CCh leading to rapid
      activation of an inward current followed by a slower outward current. 2.
      Photochemical release of inositol 1,4,5-trisphosphate (InsP3), from 'caged'
      InsP3, by a brief near-UV flash, evoked similar biphasic current responses at -40
      mV. In contrast, elevation of [Ca2+]i by photolysis of the caged calcium compound
      nitr-5 at -40 mV activated only monophasic current responses. 3. These results
      can be explained by a model in which the InsP3-sensitive Ca2+ release sites are
      localized at the luminal pole of the cell, combined with a relative preponderance
      of Ca(2+)-activated Cl- channels at that pole, and a relative preponderance of
      Ca(2+)-activated K+ channels at the basal end.

PMID- 7525952
TI  - Relationships among GnRH, substance P, prostaglandins, sex steroids and aromatase
      activity in the brain of the male lizard Podarcis sicula sicula during
      reproduction.
AB  - The release of PGF2 alpha and PGE2, progesterone, androgens and oestradiol in
      vitro, and the aromatase activity in the brain of the male lizard Podarcis sicula
      sicula during three different phases of the reproductive period were evaluated.
      In addition, the effects of salmon GnRH, substance P, salmon GnRH antagonist,
      substance P antagonist, PGF2 alpha, PGE2 and acetylsalicylic acid on the release
      of prostaglandins and sex steroids and on aromatase activity in the brain were
      evaluated during the same three phases. PGF2 alpha, oestradiol and aromatase
      activity were higher during the refractory phase, androgens during the fighting
      phase, and progesterone during the mating phase, while PGE2 was lower during the
      refractory phase. Treatment with salmon GnRH increased PGF2 alpha, oestradiol and
      aromatase activity, but decreased the amount of androgens released. Substance P
      decreased PGF2 alpha, oestradiol and aromatase activity, but increased the amount
      of androgens released. PGF2 alpha increased oestradiol and aromatase activity,
      but decreased the amount of androgens released. Acetylsalicylic acid decreased
      PGF2 alpha, oestradiol and aromatase activity, but increased the amount of
      androgens released. These data suggest that salmon GnRH and substance P have
      different roles in reproductive processes, with opposite mechanisms, in the
      central nervous system of this male lizard: salmon GnRH seems to be involved in
      regulating the refractory phase, while substance P plays a role in regulating the
      fighting phase.

PMID- 7525953
TI  - Flow cytometric and microscopic evaluation and effect on fertility of abnormal
      chromatin condensation in bovine sperm nuclei.
AB  - The techniques of Feulgen staining, acridine orange staining, and a sperm
      chromatin structure assay using acridine orange and flow cytometry were compared
      for selective examination of bovine sperm nuclei. Twenty frozen semen samples
      were simultaneously analysed by all three methods. The prevalence of abnormally
      condensed DNA and its relationship to other semen traits were determined in
      ejaculates from 70 bulbs presented for routine examination for breeding soundness
      and in frozen semen from 348 bulls evaluated over five years. A breeding trial
      with 118 beef heifers using semen from six bulls with different degrees of
      nuclear abnormalities was performed to assess the importance of the defects with
      respect to fertility. The results indicate that few spermatozoa with abnormal DNA
      condensation are found in normal semen, but the incidence increases with
      disturbance of spermatogenesis. However, high numbers of abnormally condensed
      nuclei were found in the absence of an increase in other defects. This nuclear
      defect might be at least partially of epididymal origin; it can lower fertility
      and can be compensated for by increasing the numbers of normal spermatozoa in the
      insemination dose. The percentage of abnormally condensed sperm nuclei as
      detected by Feulgen staining was significantly correlated with that detected by
      microscopy after acridine orange staining and by the sperm chromatin structure
      assay. We therefore consider the Feulgen technique to be a valuable tool for
      assessing the nuclear integrity of bovine spermatozoa.

PMID- 7525954
TI  - Successful pregnancy in a woman with cyanotic congenital heart disease after a
      palliative pulmonary-systemic shunt. A case report.
AB  - A 20-year-old woman with cyanotic congenital heart disease composed of corrected
      transposition of the great vessels, severe pulmonic stenosis, atresia of the left
      pulmonary artery and a large ventricular septal defect, had a successful
      pregnancy following a pulmonary-systemic shunt (Blalock-Taussig). The hemoglobin
      decreased from 21 to 16 g/dL following the operation. The antepartum course was
      complicated by intrauterine growth retardation and pregnancy-induced
      hypertension. A normal fetal nonstress test and biophysical profile permitted
      continuation of the pregnancy until 38 weeks' gestation, with delivery of a
      healthy infant.

PMID- 7525956
TI  - Rheumatoid arthritis in Tlingit Indians: clinical characterization and HLA
      associations.
AB  - OBJECTIVE: To characterize the features of rheumatoid arthritis (RA) in Tlingit
      Indians, to identify the HLA-DR alleles associated with RA in the Tlingit, and to
      determine whether disease severity or specific clinical manifestations correlate
      with the presence of specific HLA antigens. METHOD: Thirty-seven Tlingit patients
      with RA and 75 controls were evaluated clinically; comparative HLA studies were
      carried out in 33 patients and 62 controls. RESULTS: The results of this clinical
      study of RA in the Tlingit confirms that the disease found in them is classical
      RA, characterized by an early age of onset, a high frequency of nodules, serum
      rheumatoid factor (RF) and antinuclear antibodies (ANA); an often severe clinical
      course, with a high frequency of erosive disease and frequent need for surgical
      joint repair, and an often positive family history. In Tlingit volunteers who did
      not have RA we also found an increased prevalence of RF and ANA. Neither HLA-DR1
      nor DR4 was found to be associated with RA in the Tlingit. The commonest DR
      antigen in patients with RA was DR14. The most frequent DRB1 allele was DRB1*1402
      (Dw16). CONCLUSION: The Tlingit population had a very high frequency of the
      DRB1*1402 allele, which shares key sequence homology with DRB1*0401 (Dw4) and
      DRB1*0101 (Dw1), associated with RA in other racial groups. No correlations were
      found between specific HLA-DRB1 alleles or combinations of alleles and specific
      disease features or severity.

PMID- 7525957
TI  - Localization of endothelin-1 and its binding sites in scleroderma skin.
AB  - OBJECTIVE: Endothelin-1 (ET-1) has been implicated in the pathogenesis of
      systemic sclerosis (SSc) as it is both a potent vasoconstrictor and fibroblast
      mitogen and is raised in the circulation of patients with SSc and primary
      Raynaud's phenomenon. METHODS: We examined the localization and level of
      expression of ET-1 and its putative receptors in clinically "uninvolved" (i.e.,
      prescleroderma skin) and involved skin from patients with diffuse cutaneous
      systemic sclerosis (dcSSc), using the alkaline phosphatase antialkaline
      phosphatase technique while ET-1 binding sites were examined using in vitro
      autoradiography. RESULTS: There was an increase in dermal ET-1 staining in
      clinically uninvolved and involved skin from patients with early active dcSSc
      compared with late stage fibrotic SSc skin and normal skin from healthy
      volunteers. Increased ET-1 staining was associated predominantly with the
      superficial vessels in the SSc skin sections. In addition, there was a
      significant increase in [125I]ET-1 binding to superficial vessels and the
      dermal/epidermal junction in SSc skin compared with the binding to similar
      structures in normal tissue. There was no change in [125I]ET-1 binding to the
      deep dermal vessels in both SSc and normal skin. This increase in [125I]ET-1
      binding in SSc skin was not maintained with increasing tissue fibrosis.
      CONCLUSION: The presence of increased ET-1 levels as well as its binding sites in
      both the prescleroderma and involved skin of patients with dcSSc compared to
      controls suggests that ET-1 may play a role in the pathology of dermal fibrosis
      and vasoconstriction in SSc.

PMID- 7525955
TI  - Specificity of antibodies to type II collagen in early rheumatoid arthritis.
AB  - OBJECTIVE: To analyze the antibody response to native type II collagen in early
      rheumatoid arthritis (RA), examining the immunoglobulin isotypes, and polypeptide
      epitopes recognized, in patients followed over a 2-year period from within 6
      months of the first occurrence of symptoms. METHODS: Sera from 16 patients were
      studied, of whom 10 had antibodies to native type II collagen and 6 did not. The
      clinical and laboratory assessment, carried out initially and at 6 monthly
      intervals included the number of 1958 ARA criteria fulfilled, Ritchie index,
      erythrocyte sedimentation rate, rheumatoid factor and radiological assessment. An
      ELISA was used to measure IgG, IgA and IgM antibodies, and immunoblotting to
      identify the number and location of epitopes, using polypeptides prepared by
      cyanogen bromide digestion of human type II collagen. RESULTS: Antibodies to type
      II collagen were present in all sequential serum samples for the 10 antibody
      positive patients. None of the 6 patients who initially lacked antibodies
      developed them. The antibodies were of IgG isotype in 9, of IgA isotype in 8, and
      of IgM isotype exclusively in one. At the initial clinical assessment patients
      with antibodies to collagen were indistinguishable from those without. At 12 and
      24 months patients with antibodies fulfilled significantly more ARA criteria than
      antibody negative patients. The patterns of antibody reactivity to collagen
      polypeptides by immunoblotting were constant over time but differed from patient
      to patient. CONCLUSION: The presence of an established and persisting IgG
      antibody response to type II collagen in early RA before cartilage destruction is
      evident points to a subset of RA, perhaps equivalent to the collagen induced
      model in animals, in which this immune response is intrinsic to pathogenesis.

PMID- 7525958
TI  - Novel acyclic nucleotides and nucleoside 5'-triphosphates imitating 2',3'-dideoxy
      2',3'-didehydronucleotides: synthesis and biological properties.
AB  - A series of pyrophosphoryl (Z)-(phosphonomethoxy)but-2-enyl derivatives of
      pyrimidines and purines 9a-d and the corresponding phosphonates 10a-d were
      synthesized. The prepared compounds contain the phosphonate group as an alpha
      phosphate mimic as well as an acyclic residue emulating the sugar moiety in 2',3'
      dideoxy-2',3'-didehydronucleoside 5'-triphosphates known as highly potent chain
      terminators of DNA polymerases. Phosphonates 10a-d were obtained by alternative
      alkylations of the nucleic bases followed by condensation with ethyl [[(p
      tolylsulfonyl)oxy]methyl]phosphonate. Pyrophosphorylation of 10a-d afforded
      phosphonate diphosphates 9a-d. Their substrate properties were evaluated in cell
      free systems containing various DNA polymerases including viral reverse
      transcriptases. Compounds 9a-d manifested good terminating substrate properties
      toward HIV-1 and AMV reverse transcriptases. They exhibited high selectivity and
      were not recognized by human DNA polymerases alpha and epsilon, DNA polymerase
      beta from rat liver, Escherichia coli DNA polymerase I, and HSV-1 and CMV DNA
      polymerases. Phosphonates 10b-d displayed no activity in HIV-1-infected MT-4
      cells cultures; 10a was moderately effective (ED50 = 9 microM).

PMID- 7525960
TI  - The synthesis of nucleoside 5'-O-(1,1-dithiotriphosphates).
AB  - Appropriately protected nucleoside 5'-O-(2-thio-1,3,2-dithiaphospholanes) react
      with inorganic pyrophosphate in the presence of a strong base catalyst (DBU) to
      give nucleoside 5'-O-(1,1-dithiotriphosphates) 1a-g. The latter compounds,
      including an AZT analogue, show modest antivirial activity against HIV-1 and HIV
      2 replication in CEM cells. The AZT and deoxyadenosine derivatives were found to
      be inhibitors of HIV reverse transcriptase.

PMID- 7525961
TI  - L-N6-(1-iminoethyl)lysine: a selective inhibitor of inducible nitric oxide
      synthase.
AB  - L-N6-(1-Iminoethyl)lysine (L-NIL) has been synthesized and is shown to be both a
      potent and selective inhibitor of mouse inducible nitric oxide synthase (miNOS).
      L-NIL has an IC50 of 3.3 microM for miNOS compared to an IC50 of 92 microM for
      rat brain constitutive NOS indicating that L-NIL is 28-fold more selective for
      inducible NOS. L-N5-(1-Iminoethyl)ornithine (L-NIO), which differs from L-NIL by
      having one less methylene group, has very similar potency for inducible NOS, but
      lacks selectivity. DL-N7-(1-Iminoethyl)homolysine was also synthesized and found
      to be substantially less potent than L-NIL or L-NIO, with intermediate
      selectivity for inducible NOS. These data suggest that L-NIL may be useful as a
      selective inhibitor of inducible NOS for determining the role of this enzyme in
      disease models.

PMID- 7525962
TI  - Anti-AIDS agents. 15. Synthesis and anti-HIV activity of dihydroseselins and
      related analogs.
AB  - Forty-two dihydroseselins based on the structure of suksdorfin (1) were
      synthesized in order to evaluate their anti-HIV activity. These synthetic
      derivatives include 3',4'-di-O-acyl- and 3'- or 4'-O-acyl-cis-dihydroseselins (8
      21) and 3',4'-trans-dihydroseselins with O-acyl and/or O-alkyl groups at the 3'
      and 4' positions (6, 22-43). Two 4'-azido (44, 45) and three 4'-alkylamido (46,
      48, 49) derivatives were also prepared. By using optically pure reagents, three
      pairs of diastereoisomers were synthesized and separated as optically pure
      compounds (14, 15; 16, 17; 38, 39). Together with the above synthetic
      derivatives, seselin (3) and (+/-)-cis-(4), (+)-cis- (5), and (+/-)-trans
      dihydroseselin-3',4'-diol (7) were also tested for their in vitro anti-HIV
      activity. An optically pure compound, 3',4'-di-O-(-)-camphanoyl-(+)-cis
      khellactone (16), showed potent inhibitory activity and remarkable selectivity
      against HIV replication. The EC50 value and in vitro therapeutic index (TI) of 16
      are 4 x 10(-4) microM and 136,719, respectively, which are better than those
      shown by AZT in the same assay. In addition, compound 16 is also active against
      HIV replication in a monocytic cell line and in peripheral blood mononuclear
      cells (PBMCs). Our in vitro assay indicated that, like compound 1, compound 16 is
      not an inhibitor of HIV-1 reverse transcriptase. Moreover, the anti-HIV activity
      of 16 is stereoselective as its three diastereoisomers (17, 38, 39) are at least
      10,000 times less active. Since other synthetic dihydroseselin derivatives with
      different substituents or without any substituents are inactive or are active
      only at much higher concentration, the antiviral potency of 16 could be
      associated with the camphanoyl moieties of its structure. Therefore, compound 16
      represents a unique coumarin structure with promising anti-HIV activity.

PMID- 7525963
TI  - Mutation analysis in 600 French cystic fibrosis patients.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) gene of 600
      unrelated cystic fibrosis (CF) patients living in France (excluding Brittany) was
      screened for 105 different mutations. This analysis resulted in the
      identification of 86% of the CF alleles and complete genotyping of 76% of the
      patients. The most frequent mutations in this population after delta F508 (69% of
      the CF chromosomes) are G542X (3.3%), N1303K (1.8%), W1282X (1.5%), 1717-1G-->A
      (1.3%), 2184delA + 2183 A-->G (0.9%), and R553X (0.8%).

PMID- 7525959
TI  - Inhibition of topoisomerase II catalytic activity by pyridoacridine alkaloids
      from a Cystodytes sp. ascidian: a mechanism for the apparent intercalator-induced
      inhibition of topoisomerase II.
AB  - Several new pyridoacridine alkaloids, dehydrokuanoniamine B (1), shermilamine C
      (2), and cystodytin J (3), in addition to the known compounds cystodytin A (4),
      kuanoniamine D (5), shermilamine B (6), and eilatin (7), were isolated from a
      Fijian Cystodytes sp. ascidian. Their structures were determined by analyses of
      spectroscopic data. These compounds along with a previously reported
      pyridoacridine, diplamine (8), showed dose-dependent inhibition of proliferation
      in human colon tumor (HCT) cells in vitro. All compounds inhibited the
      topoisomerase (TOPO) II-mediated decatenation of kinetoplast DNA (kDNA) in a dose
      dependent manner. The pyridoacridines' ability to inhibit TOPO II-mediated
      decatenation of kDNA correlated with their cytotoxic potencies and their ability
      to intercalate into calf thymus DNA. These results suggest that disruption of the
      function of TOPO II, subsequent to intercalation, is a probable mechanism by
      which pyridoacridines inhibit the proliferation of HCT cells. Incorporation
      studies show that pyridoacridines disrupt DNA and RNA synthesis with little
      effect on protein synthesis. It appears that DNA is the primary cellular target
      of the pyridoacridine alkaloids. These results are consistent with those for
      known DNA intercalators.

PMID- 7525964
TI  - Evaluation of laboratory methods for cystic fibrosis carrier screening:
      reliability, sensitivity, specificity, and costs.
AB  - We report a comparative evaluation of three different laboratory methods for
      screening large numbers of mouthwash DNA samples for common cystic fibrosis
      mutations. Sensitivity, specificity, and costs of ARMS (allele refractory
      mutation detection system), dot blotting, and a deletion/digest/PAGE method
      (multiplex PCR of exons 10 and 11, digest with HincII followed by polyacrylamide
      gel electrophoresis (PAGE)) were assessed. ARMS was the most reliable and
      sensitive method and so was considered more suitable than the cheaper
      deletion/digest/PAGE. As well as being less reliable than ARMS, the dot blotting
      method assessed was considerably more costly. ARMS was the best laboratory method
      for CF screening tested.

PMID- 7525966
TI  - Locations of anti-AIDS drug binding sites and resistance mutations in the three
      dimensional structure of HIV-1 reverse transcriptase. Implications for mechanisms
      of drug inhibition and resistance.
AB  - The locations of HIV-1 RT nucleoside and non-nucleoside inhibitor-binding sites
      and inhibitor-resistance mutations are analyzed in the context of the three
      dimensional structure of the enzyme and implications for mechanisms of drug
      inhibition and resistance are discussed. In order to help identify residues that
      may play a role in inhibitor binding, solvent accessibilities of amino acids that
      comprise the inhibitor-binding sites in the structure of HIV-1 RT complexed with
      a dsDNA template-primer are analyzed. While some mutations that cause resistance
      to nucleoside analogs, such as AZT, ddI, and ddC, are located near enough to the
      dNTP-binding site to directly interfere with binding of nucleoside analogs, many
      are located away from the dNTP-binding site and more likely confer resistance by
      other mechanisms. Many of the latter mutations are located on the surface of the
      DNA-binding cleft and may lead to altered template-primer positioning or
      conformation, causing a distortion of the geometry of the polymerase active site
      and consequent discrimination between normal and altered dNTP substrates. Other
      nucleoside analog-resistance mutations located on the periphery of the dNTP
      binding site may exert their effects via altered interactions with dNTP-binding
      site residues. The structure of the hydrophobic region in HIV-1 RT that binds non
      nucleoside inhibitors, for example, nevirapine and TIBO, has been analyzed in the
      absence of bound ligand. The pocket that is present when non-nucleoside
      inhibitors are bound is not observed in the inhibitor-free structure of HIV-1 RT
      with dsDNA. In particular it is filled by Tyr181 and Tyr188, suggesting that the
      pocket is formed primarily by rotation of these large aromatic side-chains.
      Existing biochemical data, taken together with the three-dimensional structure of
      HIV-1 RT, makes it possible to propose potential mechanisms of inhibition by non
      nucleoside inhibitors. One such mechanism is local distortion of HIV-1 RT
      structural elements thought to participate in catalysis: the beta 9-beta 10
      hairpin (which contains polymerase active site residues) and the beta 12-beta 13
      hairpin ("primer grip"). An alternative possibility is restricted mobility of the
      p66 thumb subdomain, which is supported by the observation that structural
      elements of the non-nucleoside inhibitor-binding pocket may act as a "hinge" for
      the thumb.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7525965
TI  - Triton channels are sensitive to divalent cations and protons.
AB  - Addition of Triton X-100 to planar bilayers composed of dioleoyl phosphatidyl
      choline, diphytanoyl phosphatidyl choline or mono-oleoyl glycerol induces single
      channel-like events when electrical conductivity across the bilayer is measured.
      Addition of divalent cations or protons causes channels to disappear; single
      channel conductance of remaining channels is not significantly altered; addition
      of EDTA or alkali (respectively) reverses the effect. It is concluded that
      sensitivity to divalent cations and protons need not be dependent on specific
      channel proteins or pore-forming toxins, but may be a feature of any aqueous pore
      across a lipid milieu.

PMID- 7525967
TI  - Mutational analysis of the fingers and palm subdomains of human immunodeficiency
      virus type-1 (HIV-1) reverse transcriptase.
AB  - We have analyzed the human immunodeficiency virus type-1 reverse transcriptase
      (HIV-1 RT) polymerase domain between amino acids 91 and 157 by site-directed
      mutagenesis. We have constructed a series of amino acid substitutions using BspMI
      cassettes, and have assayed the RNA-dependent DNA polymerase, DNA-dependent DNA
      polymerase, and RNase H activities of the mutant HIV-1 RTs. The regions of HIV-1
      RT between amino acids 91 and 119 and between amino acids 151 and 157 lie within
      the palm subdomain and include part of the polymerase active site. A number of
      amino acids within these regions have been identified as being directly or
      indirectly involved with polymerization, since amino acid substitutions at these
      residues decrease the polymerase activity without affecting RNase H activity. The
      region of HIV-1 RT between amino acids 120 and 150 lies within the fingers
      subdomain of the HIV-1 polymerase. We believe that the fingers subdomain plays a
      role in positioning the template. Many amino acid substitutions in this region
      decrease or abolish both the polymerase and the RNase H functions.

PMID- 7525969
TI  - Human immunodeficiency virus type 1 tat directs transcription through attenuation
      sites within the mouse c-myc gene.
AB  - The regulation of transcriptional elongation plays a central role in the
      expression of a number of cellular and viral genes. For example, levels of c-myc
      RNA change during cellular proliferation and differentiation via alterations in
      transcriptional attenuation near the 5' end of the c-myc gene. The protein that
      regulates transcription through attenuation sites in c-myc has not been
      identified. However, a candidate protein of equivalent function exists in the
      human immunodeficiency virus (HIV) genome, where the transactivator Tat increases
      transcriptional elongation through the HIV LTR and coding sequences by
      interacting with the trans-acting-response (TAR) RNA stem-loop that is found at
      the 5' end of all viral transcripts. By placing TAR 3' to the P2 promoter of the
      mouse c-myc gene, we demonstrate that Tat can also direct read-through
      transcription in mouse c-myc in transfected HeLa cells. Thus we identified a
      viral transactivator whose cellular counterpart regulates transcriptional
      attenuation within c-myc and other proto-oncogenes.

PMID- 7525968
TI  - Kinetic analysis of the catalysis of strand transfer from internal regions of
      heteropolymeric RNA templates by human immunodeficiency virus reverse
      transcriptase.
AB  - The kinetic mechanism of HIV reverse transcriptase catalyzed strand transfer
      synthesis (i.e. switching of the primer to a new template) from internal regions
      of natural sequence RNA was investigated. The system consisted of a 142
      nucleotide RNA template (donor), primed with a specific 20 nucleotide DNA
      oligonucleotide that was used to initiate synthesis. An RNA with homology to an
      internal region of the donor was used as acceptor template. Using 32P-labeled DNA
      oligonucleotide, the primer-extension products made from full-length synthesis on
      the donor (108 bases in length) or homologous transfer to and extension on the
      acceptor (155 bases) were monitored. Results indicated that the maximum
      efficiency of transfer (the ratio of transfer products to donor-directed+transfer
      products x 100) in this particular system was about 25% while the theoretical
      Vmax for the rate of appearance of transfer products at infinite acceptor
      concentration was about 20-fold lower than the measured rate for full-length
      donor-directed products. The Km for acceptor template in the transfer reaction
      was about 8 nM. Experiments using the above donor template hybridized to a
      specific DNA that has been shown to transfer to the acceptor indicated that RNase
      H-mediated rapid release of this DNA from the donor while subsequent association
      with the acceptor was relatively slow.

PMID- 7525970
TI  - Protein three-dimensional structure determination and sequence-specific
      assignment of 13C and 15N-separated NOE data. A novel real-space ab initio
      approach.
AB  - The sequence-specific assignment of resonances is considered to be a requirement
      for the determination of the three-dimensional (3D) structure of a protein in
      solution by nuclear magnetic resonance methods. The main source of structural
      information is the nuclear Overhauser effect spectroscopy (NOESY) spectrum, which
      contains information about spatially close pairs of protons. Currently, various J
      correlated spectra must be recorded in order to obtain the sequence-specific
      assignments necessary to interpret the NOESY spectra. In this work, a novel
      procedure to determine the 3D structure and the sequence-specific assignments of
      a protein using only data from 13C and 15N-separated multidimensional NOESY
      spectra is described. No information from J-correlated spectra is required. The
      algorithm is called ANSRS (Assignment of NOESY Spectra in Real Space) and is
      based on an inversion of the traditional strategy. A 3D real-space structure of
      detected, but unassigned, 1H spins is calculated from the nuclear Overhauser
      effect (NOE) distance restraints using a dynamical simulated annealing procedure.
      The sequence-specific assignments are then determined by searching among the 1H
      spins in the 3D real-space structure for plausible residue assignments. The
      search uses a Monte Carlo simulated annealing algorithm based on assignment
      probabilities derived from the 1H, 15N and 13C chemical shifts, various spatial
      constraints, and the known sequence of the protein. The procedure has been tested
      on semi-synthetic data sets comprising published experimental chemical shifts and
      NOE distance restraints derived from the known 3D structures of the two proteins
      GAL4 (residues 9 to 41) and bovine pancreatic trypsin inhibitor. The ANSRS
      procedure was able to determine the sequence-specific assignments for more than
      95% of the spins, and was fairly robust with respect to missing NOE data. The
      potential of the ANSRS approach with respect to automated assignment, reduction
      of the number of NMR spectra required for a structure determination, assignment
      of homologous and mutant proteins, and the possibility of analysing spectra
      recorded at high pH is discussed.

PMID- 7525971
TI  - Studies of the interactions between Escherichia coli ribonuclease HI and its
      substrate.
AB  - Ribonuclease H (RNase H) recognizes a DNA-RNA hybrid duplex and catalyzes the
      hydrolysis of the phosphodiester linkages in only the RNA strand. Previously, we
      developed a method to cleave RNA in a sequence-dependent manner using RNase H and
      a complementary oligonucleotide containing 2'-O-methylribonucleosides. Since
      cleavage is restricted to a single site by the modified complementary strand,
      this system allows kinetic analysis of the RNase H reaction. We describe an
      investigation of the interactions between RNase HI from Escherichia coli and its
      substrate, and between the substrate and a metal ion using synthetic
      oligonucleotide duplexes modified at the cleavage site in combination with the 2'
      O-methylribonucleotides. Firstly, the base moiety was changed to interfere with
      enzyme binding in either the major or minor groove. When 2-N-methylguanine was
      incorporated into the cleavage site, the Km value for this substrate, containing
      a methyl group in the minor groove, was 20-fold larger than that for the
      unmodified substrate, whereas 5-phenyluracil, with a phenyl group residing in the
      major groove of the duplex, did not affect the affinity. Secondly, the
      phosphodiester linkage at the cleavage site was changed into a phosphorothioate
      with a defined configuration. Only the Rp isomer was cleaved at this site in the
      presence of Mg2+ or Cd2+. These results suggest that the enzyme, but not the
      metal ion, interacts with the phosphate residue at the cleavage site. Thirdly,
      the 2'-position of the nucleoside on the 5'-side of the scissile phosphodiester
      was modified. Alteration of the 2'-hydroxyl function into an amino, fluoro or
      methoxy group, or removal of this 2'-hydroxyl group, did not affect the affinity
      for the enzyme, but reduced the reaction rate. An outer sphere interaction of a
      metal ion with the 2'-hydroxyl group is suggested.

PMID- 7525972
TI  - A quaternary transcription termination complex. Reciprocal stabilization by Rho
      factor and NusG protein.
AB  - The Escherichia coli protein NusG is known to modulate Rho-dependent
      transcription termination in vivo. We have shown that it can also alter the
      pattern of Rho-dependent RNA endpoints in vitro, at lower NusG concentrations
      than can be explained by reported interactions between NusG and Rho or RNA
      polymerase. Three observations in vitro now suggest a model to account for these
      effects of NusG on Rho-dependent termination. First, the presence of NusG
      circumvents the interference with Rho function caused by adding DNA
      oligonucleotides complementary to particular segments of the Rho binding site.
      Second, when NusG is added to stalled elongation complexes, the off-rate of Rho
      from nascent RNA is slowed. Third, NusG associates stably with the elongation
      complex only when Rho is also present and bound to the nascent RNA. Our
      observations are consistent with a model in which NusG and Rho participate in an
      interdependent association with the transcribing RNA polymerase and the nascent
      RNA to facilitate the recognition and use of termination signals. Common
      structural and functional features shared with complexes that carry out
      processive antitermination are discussed.

PMID- 7525973
TI  - Refined structure of the porin from Rhodopseudomonas blastica. Comparison with
      the porin from Rhodobacter capsulatus.
AB  - The structure of the membrane channel porin from the phototrophic bacteria
      Rhodopseudomonas blastica has been refined at 1.96 A resolution yielding an R
      factor of 17.6%. The final model consists of all 289 amino acid residues, 247
      water molecules and three detergent molecules modelled as n
      octyltetraoxyethylene. One of these detergent molecules binds together with its
      two symmetry-related molecules tightly in a pocket at the molecular 3-fold axis.
      This pocket may bind three alkyl chains of a lipopolysaccharide which in turn
      would stabilize the trimer and could possibly play a role in membrane insertion.
      The overall shape of this porin resembles OmpF of Escherichia coli more than the
      only known sequence-related porin from Rhodobacter capsulatus. The membrane
      contacting surface is similar in all structurally known porins; it shows
      exceptional frequencies of amino acid residues and side-chain rotamers. The 46
      residue loop beta 5-beta 6 of the porin is shown to be tightly fastened to the
      beta-barrel, excluding an in vivo loop movement that closes the pore. The trimer
      interface region has the structure of a water-soluble protein with an extensive
      non-polar core and numerous hydrogen bonds at the surface. The loops at the
      external end of the barrel are long and rigid whereas those at the periplasmic
      barrel end are short and mobile. The crystal packing is discussed.

PMID- 7525974
TI  - Excess counterion accumulation around branched nucleic acids.
AB  - Many nucleic acids of biological importance possess elements of tertiary
      structure in which the regional phosphate charge density dramatically exceeds
      that of linear duplex DNA, as in the inter-helix junctions found in tRNAs,
      ribosomal RNAs, and Holliday intermediates in general recombination. However,
      despite a long-standing awareness that such structures have special counterion
      requirements for stability few studies have focused on their level of counterion
      association. In order to gauge the influence of high regional phosphate charge
      density on the extent of counterion association, we have defined the degree of
      "excess counterion association" for a four-branch DNA junction as the number of
      additional counterions (over the relevant linear DNA value) that are associated
      with the junction in a Donnan equilibrium dialysis experiment. Grand canonical
      Monte Carlo computations were used to determine the Donnan distribution
      (preferential interaction) coefficients, employing a "primitive model"
      description of the nucleic acid and the 1:1 electrolyte. We have determined that
      at least 24 excess counterions are associated with the junction in the long
      branch limit. The subsequent release of a portion of these additional counterions
      during the process of ligand binding is therefore likely to provide a strong
      directional influence on the binding of proteins and cationic ligands, with
      preferred binding near or on the junction vertex or near other elements of
      tertiary structure (e.g. pseudo-knots or triplexes) even if the ligands do not
      directly recognize the structural elements themselves. Moreover, excess
      counterion association is expected to play a significant role in determining the
      relative stabilities of alternative tertiary structures.

PMID- 7525975
TI  - 11-fold symmetry of the trp RNA-binding attenuation protein (TRAP) from Bacillus
      subtilis determined by X-ray analysis.
AB  - The trp RNA-binding attenuation protein (TRAP) of Bacillus subtilis has been
      crystallized and examined by crystallography using X-ray synchrotron radiation
      diffraction data. Crystals of TRAP complexed with L-tryptophan belong to space
      group C2 with a = 156.8 A, b = 114.05 A, c = 105.9 A, beta = 118.2 degrees.
      Crystals of a potential heavy-atom derivative of TRAP complexed with 5-bromo-L
      tryptophan grow in the same space group with similar cell dimensions. X-ray data
      for the native crystals and for the derivative have been collected to 2.9 A and
      2.2 A resolution, respectively. Peaks in the self-rotation function and in the
      Patterson synthesis could only be explained by two 11-subunit oligomers (each
      formed by an 11-fold axis of symmetry) in the asymmetric unit lying with the 11
      fold rotation axes parallel to each other. The consequence is that the TRAP
      molecule has 11-fold symmetry and contains 11 subunits.

PMID- 7525976
TI  - Mutational and structural analysis of the RNA binding site for Escherichia coli
      ribosomal protein S7.
AB  - Ribosomal protein S7 binds to a small RNA fragment of about 100 nucleotides
      within the lower half of the 3' major domain of E. coli 16 S rRNA. This fragment
      (D3M) comprises two large internal loops, A and B, connected by helix 29, a six
      base-pair helix containing a G.U pair. Two hairpins with non-canonical base
      pairs, 42' and 43, protrude from loops A and B, respectively. We used site
      directed mutagenesis and molecular probing to further define which parts of D3M
      are important for S7 binding. Changing the stem of hairpin 42' into a Watson
      Crick helix did not affect S7 binding, indicating that the non-canonical pairs of
      42' do not provide recognition features for S7. However, deletion of this hairpin
      decreased S7 binding affinity by about threefold and altered the conformation of
      loop A. Deletion of the upper part of hairpin 43 (the loop and the adjacent four
      base-pairs) did not affect S7 binding, whereas the lower part of this hairpin
      (three base-pairs) was found to be required for proper S7 binding. Moreover,
      replacing the U.G pair with a C.G pair in this lower part decreased S7 binding
      affinity by twofold, suggesting that the U.G pair is a recognition signal for S7.
      S7 binding was also affected by mutations in helix 29. Insertion of one
      nucleotide 5' to the G or 3' to the U of the G.U pair decreased S7 binding
      affinity by about threefold and twofold, respectively, whereas replacement of the
      G.U pair by a G.C pair enhanced the affinity about twofold, and lengthening the
      helix by inserting a C.G pair upstream from the G.U pair had no effect. Taken
      together, these results are consistent with a bipartite binding site for S7 on 16
      S rRNA, involving two regions of interaction: one centered around helix 29 and
      extending on the adjacent part of loop A, and the other one centered around the
      lower part of hairpin 43 and probably extending on the adjoining part of loop B.

PMID- 7525977
TI  - Pars plana vitrectomy for subfoveal macular hemorrhage and choroidal neovascular
      membranes.
AB  - 1. Choroidal neovascular membranes (CNVM), the abnormal ingrowth of blood vessels
      from the choroid through Bruch's membrane, remain a major cause of treatable
      visual loss. 2. Laser photocoagulation is effective in destroying CNVM and
      preserving central vision in many affected patients. However, laser treatment of
      subfoveal CNVM irreversibly destroys foveal vision. 3. The utility of vitrectomy
      techniques for removal of subfoveal macular hemorrhage on CNVM remains unknown
      pending the results of a randomized, controlled prospective study. 4. Laser
      photocoagulation remains the treatment of choice for extra- and juxtafoveal CNVM
      caused by age-related macular degeneration (ARMD), ocular histoplasmosis and
      idiopathic causes, and for selected subfoveal CNVM caused by ARMD.

PMID- 7525978
TI  - Prognostic significance of insulin-like growth factor-binding protein expression
      in axillary lymph node-negative breast cancer.
AB  - BACKGROUND: Cellular proliferation, as measured by S-phase fraction, is an
      important predictor of breast cancer prognosis. The insulin-like growth factors
      (IGFs) have been shown to regulate proliferation in both normal and neoplastic
      cells by interacting with specific cell surface receptors. In addition to these
      receptors, high-affinity extracellular binding proteins also modulate IGF action.
      These insulin-like growth factor-binding proteins (IGFBPs) could influence breast
      cancer growth and, like other biological parameters of proliferation, could be
      related to prognosis. PURPOSE: To test whether IGFBP expression was related to
      other biological parameters and disease-free survival, we measured IGFBP
      expression in 238 lymph node-negative primary breast cancer specimens. METHODS:
      Proteins were extracted from breast cancer specimens and analyzed by
      semiquantitative IGF-I ligand blotting for IGFBP expression. IGFBP expression
      levels were compared to tumor size, age, S-phase fraction, DNA ploidy, and
      estrogen and progesterone receptor expression by Spearman correlation. RESULTS:
      Binding protein (BP)-2, BP-3, BP-4, and BP-5 were identified in breast cancer
      extracts. Estrogen receptor expression was positively correlated with BP-2
      (Spearman correlation coefficient, rs = .262; P = .0001), BP-4 (rs = .313; P =
      .0001), and BP-5 (rs = .242; P = .0002). Similar correlations between
      progesterone receptor and BP-2, BP-4, and BP-5 were also found. BP-3 was
      inversely correlated with age (rs = -.251, P = .0001). BP-4 was weakly inversely
      correlated with tumor size (rs = -.141; P = .0295) and S-phase fraction (rs = 
      .216; P = .0025). Since tumor size and S-phase fraction are powerful predictors
      of prognosis in node-negative breast cancer, we examined the value of BP-4 as a
      predictor of disease-free survival. When stratified by tumor size, patients with
      large (> 2 cm) tumors that expressed low levels of BP-4 had improved survival
      when compared with patients with large tumors and high BP-4 levels (P = .001).
      CONCLUSIONS: IGFBPs can be detected in breast cancer specimens, and their level
      of expression correlates with other known biological parameters of breast cancer.
      Large tumors with low levels of BP-4 have relatively favorable prognoses.
      IMPLICATIONS: These data suggest that the IGFBPs may play a role in breast cancer
      biology and that BP-4 levels, analyzed in conjunction with tumor size, may have
      prognostic significance.

PMID- 7525979
TI  - Serum PSA and PAP measurements discriminating patients with prostate carcinoma
      from patients with nodular hyperplasia.
AB  - Prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) are the
      tumor markers for monitoring disease progression or improvement in patients with
      prostate adenocarcinoma. The clinical utility of PSA and PAP for early detection
      of prostate adenocarcinoma, however, requires distinction between prostate
      adenocarcinoma and prostate nodular hyperplasia. The serum PSA and PAP levels
      were measured in 20 men with histologically proven prostate adenocarcinoma and 28
      men with histologically proven prostate nodular hyperplasia. Patients' blood
      samples were collected 1 to 7 days prior to the prostate examination, which
      included a rectal digital examination, transurethral resection, cytoscopy, and
      prostate biopsy. Sensitivity, specificity, and predictive values of positive and
      negative results for the discrimination of prostate adenocarcinoma from prostate
      nodular hyperplasia were 85%, 89%, 85%, and 29%, respectively, for serum PSA
      (cutoff level: 10 ng/mL) and 40%, 96%, 89%, and 69%, respectively, for serum PAP
      (cutoff level: 10 ng/mL). Results indicate that marked elevation of serum PSA
      suggests prostate adenocarcinoma and that serum PSA can discriminate prostate
      adenocarcinoma from prostate nodular hyperplasia better than serum PAP.

PMID- 7525981
TI  - An effective method for depleting mature T lymphocytes from bone marrow cells-
      two-step Percoll centrifugation.
AB  - In the present paper we have observed the effect of discontinuous gradient two
      step Percoll centrifugation on depleting mature T lymphocytes from normal bone
      marrow. The pre-/post-Percoll percentage of CD34+, and Leu4+ cells in MNC was
      counted by using APAAP technique. As the two-step Percoll centrifugation is
      simple, and time saving, and decreases the incidence of contamination of cultured
      cells as well, This technique may be of value in serum-free culture of
      hematopoietic cells and immunological studies.

PMID- 7525980
TI  - Observations on the contraction and movement of fat-storing cells in culture.
AB  - The Wistar fat-storing cells were isolated by perfusion with collagenase and
      centrifugation with metrizamide density cushion technique and cultured in vitro.
      The fat-storing cells were confirmed by the presentation of the lipid drop in the
      cytoplasm and the visualization of dismin with anti-dismin antibody by using
      indirect immunofluorescence method. By the videotape recorder (VIR) and the
      imagine analysis system, we observed the wandering immigration, the abrupt
      contraction of fat-storing cells with spike, then becoming a ball-like shape in
      its division phase. After that the cell began to extend and the contraction of
      these cells can be induced by the presence of 10(-2) mmol/L endothelin-1, 1
      mmol/L of substance P and 2 x 10(-5) mmol/L noradrenalin. After removal of these
      agents the contracted cells would become extended. All these findings indicate
      that the fat-storing cells have ability of contraction and movement.

PMID- 7525983
TI  - Fine structure of a virus-encoded helper T-cell epitope expressed on FBL-3 tumor
      cells.
AB  - Antigen peptide fn20 representing Friend murine leukemia virus env122-141
      (DEPLTSLTPRCNTAWNRLKL) is recognized by two independent Friend virus-induced, FBL
      3 tumor-specific helper T-cell (Th) clones. We isolated more Th clones from mice
      immunized with fn20 peptide. We examined the fine structure of the peptide
      required to activate a large group of fn20-specific Th clones. A systematic
      analysis of peptides of decreasing lengths eliciting Th proliferation defined the
      minimum core length as 13 amino acids (LTSLTPRCNTAWN). Functional proliferation
      and competition assays with variant peptides with alanine substitutions permitted
      the assignment of five peptide residues in two major histocompatibility complex
      interacting and three T-cell-receptor-interacting sites. Th clones were different
      in their reactivities toward peptides of various lengths and the variant
      peptides.

PMID- 7525982
TI  - The pharmacokinetics and pharmacodynamics of procainamide in horses after
      intravenous administration.
AB  - Six horses were administered either 15 or 20 mg/kg body weight (b.w.)
      procainamide (PA) as an intravenous (i.v.) dose over 10 min. The plasma
      concentrations of PA and N-acetylprocainamide (NAPA) as well as the
      pharmacodynamic effect (prolongation of the QT interval) were monitored. The PA
      plasma concentrations could be described by a one-compartment model with a t1/2
      of 3.49 +/- 0.61 h. The total body clearance of PA was 0.395 +/- 0.090 l/hr/kg
      and the volume of distribution was 1.93 +/- 0.27 l/kg. As observed after PA
      administration, NAPA (an active metabolite) had a t1/2 longer than PA of 6.31 +/-
      1.49 h. Peak NAPA concentrations (1.91 +/- 0.51 micrograms/ml) occurred at 5.2 h
      after the PA i.v. dose. The ratio of area under the curves for NAPA to PA was
      0.46 +/- 0.15 which is similar to that expected in humans classified as slow
      acetylators. Percentage change in the QT interval was examined with respect to PA
      and PA + NAPA plasma concentrations. For PA, % delta QT = 41.2 log (PA) - 13.26
      and correlations (r) ranged from 0.77 to 0.91 among the horses. In the case of
      PA+ NAPA, % delta QT = 57.3 log (PA + NAPA) - 31.83 and ranged from 0.77 to 0.90.
      No evidence of toxicity was noted with respect to changes in the PR interval.

PMID- 7525984
TI  - Resistance pattern of human immunodeficiency virus type 1 reverse transcriptase
      to quinoxaline S-2720.
AB  - The human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase
      (RT) inhibitor quinoxaline S-2720 showed a more-potent inhibitory effect on HIV-1
      induced cytopathicity in CEM cells than either nevirapine, pyridinone L-697,661,
      bis-heteroarylpiperazine (BHAP) U-88204, TSAO ([2',5'-bis-O-(tert
      butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5 "- (4-amino-1",2"-oxathiole
      2",2"-dioxide)-N3-ethylthymine, or 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1
      jk][1,4-benzodiazepin-2(I H)-one (TIBO) R82913. The quinoxaline derivative was
      also markedly more inhibitory to the mutant HIV-1 strains containing in their RT
      Ile-100, Asn-103, Ala-106, Lys-138, Cys-181, or His-188 substitutions than were
      the other HIV-1-specific RT inhibitors. Moreover, quinoxaline S-2720 totally
      prevented HIV-1 infection and emergence of drug-resistant mutant virus strains in
      CEM cell cultures at concentrations (i.e., 0.35 microM) that are 10- to 25-fold
      lower than those required for BHAP U-88204 and nevirapine to knock out the virus.
      Also, the concentration-response curve for S-2720 was markedly steeper than for
      BHAP and nevirapine, as reflected by the ratio of the 95% to the 50% antivirally
      effective concentration. Lower concentrations of quinoxaline dominantly lead to
      the appearance of the Ala-106 RT mutation, causing low-level resistance to the
      compound. At higher quinoxaline concentrations, the Glu-190 RT and/or the Cys-181
      RT mutation is added to the Ala-106 mutation, whereas at the highest quinoxaline
      concentrations, the Ala-106 mutation tends to disappear from the virus pool,
      leaving the Glu-190 RT and Cys-181 RT mutations as the only mutations conferring
      high-level resistance to the compound.

PMID- 7525985
TI  - Major receptor-binding and neutralization determinants are located within the
      same domain of the transmissible gastroenteritis virus (coronavirus) spike
      protein.
AB  - The spike glycoprotein (S) of coronavirus, the major target for virus
      neutralizing antibodies, is assumed to mediate the attachment of virions to the
      host cell. A 26-kilodalton fragment proteolytically cleaved from transmissible
      gastroenteritis virus (TGEV) S protein was previously shown to bear two adjacent
      antigenic sites, A and B, both defined by high-titer neutralizing antibodies.
      Recombinant baculoviruses expressing C-terminal truncations of the 26-kilodalton
      region were used to localize functionally important determinants in the S protein
      primary structure. Two overlapping 223- and 150-amino-acid-long products with
      serine 506 as a common N terminus expressed all of the site A and B epitopes and
      induced virus-binding antibodies. Coexpression of one of these truncated protein
      S derivatives with aminopeptidase N (APN), a cell surface molecule acting as a
      receptor for TGEV, led to the formation of a complex which could be
      immunoprecipitated by anti-S antibodies. These data provide evidence that major
      neutralization-mediating and receptor-binding determinants reside together within
      a domain of the S protein which behaves like an independent module. In spite of
      their ability to prevent S-APN interaction, the neutralizing antibodies appeared
      to recognize a preformed complex, thus indicating that antibody- and receptor
      binding determinants should be essentially distinct. Together these findings
      bring new insight into the molecular mechanism of TGEV neutralization.

PMID- 7525986
TI  - Priming of duck hepatitis B virus reverse transcription in vitro: premature
      termination of primer DNA induced by the 5'-triphosphate of fialuridine.
AB  - Hepadnaviruses employ a unique mechanism for the initiation of RNA-directed DNA
      synthesis. Initially, four bases (5'-GTAA-3') are added to a tyrosine residue of
      the viral polymerase by reverse transcription of a bulge sequence in epsilon, a
      stem-loop structure which functions as the packaging signal for pregenomic RNA.
      This protein-DNA complex acts as the primer for minus-strand elongation from the
      3' sequence, DR1. To understand this process in greater detail, we investigated
      whether the protein-mediated priming of viral DNA synthesis is affected by
      nucleotide analogs. By using cell-free expression of duck hepatitis B virus
      (DHBV) reverse transcriptase (G.-H. Wang and C. Seeger, Cell 71:663-670, 1992),
      the 5'-triphosphate of the thymidine analog fialuridine (FIAU) was shown to
      inhibit the incorporation of radiolabeled TMP into primer DNA in a dose-dependent
      manner. Inhibition by the 5'-triphosphate of FIAU (FIAU-TP) was nearly complete
      at a concentration of 10 microM. The dideoxynucleotide analogs ddGTP, ddTTP, and
      3'-azidodeoxythymidine triphosphate, known inhibitors of DHBV endogenous DNA
      polymerase, did not affect substantially the synthesis of primer DNA. Alternate
      substrate analysis suggested that FIAU is incorporated efficiently into nascent
      primer DNA as an analog of thymidine. Using site-directed mutagenesis to
      construct a mutant RNA template yielding a primer with the sequence 5'-GTAC-3',
      we demonstrated that FIAU-TP inhibited the incorporation of TMP, had no effect on
      that of dAMP, and decreased markedly the incorporation of dCMP. These results
      show that the synthesis of full-length DHBV primer DNA is inhibited by FIAU-TP
      but not by the dideoxynucleotide analogs that we tested. The significance of
      these findings as they relate to HBV DNA replication is discussed.

PMID- 7525987
TI  - Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory
      isolates of human immunodeficiency virus type 1.
AB  - A human immunoglobulin G1 lambda monoclonal antibody (MAb), 697-D, was developed
      that recognizes the V2 region of human immunodeficiency virus type 1 (HIV-1)
      gp120. Substitutions at amino acid positions 176/177, 179/180, 183/184, and 192
      to 194 in the V2 loop of gp120 each completely abolished the binding capacity of
      697-D in an enzyme-linked immunosorbent assay format. Competition analysis with
      three different neutralizing murine anti-V2 MAbs confirmed the specificity of 697
      D. The 697-D epitope is primarily conformation dependent, although there was weak
      reactivity of the MAb with a V2 peptide spanning residues 161 to 180. Treatment
      of recombinant gp120 HIVIIIB with sodium metaperiodate, which oxidizes
      carbohydrates, abolished the binding of the MAb, showing the dependence of the
      epitope on intact carbohydrates. The broad reactivity of 697-D was displayed by
      its binding to the gp120 molecules from four of four laboratory isolates and five
      of five primary isolates. The MAb 697-D neutralized three out of four primary
      isolates but failed to neutralize any of four laboratory strains of HIV-1. 697-D
      and a human anti-V3 MAb, 447-52-D, displayed similar potency in neutralizing
      primary isolates, indicating that the V2 region of gp120, like the V3 region and
      the CD4-binding domain, can induce potent neutralizing antibodies against HIV-1
      in humans.

PMID- 7525989
TI  - Proteolytic processing of reovirus is required for adherence to intestinal M
      cells.
AB  - Reovirus adheres specifically to apical membranes of mouse intestinal M cells and
      exploits M-cell transepithelial transport activity to enter Peyer's patch mucosa,
      where replication occurs. Proteolytic conversion of native reovirus to
      intermediate subviral particles (ISVPs) occurs in the intestine, but it is not
      known whether conversion is essential for interaction of virus with M cells. We
      tested the capacity of native virions, ISVPs, and cores (that lack outer capsid
      proteins) to bind to intestinal epithelial cells in vivo and found that only
      ISVPs adhered to M cells. Thus, intraluminal conversion of native reovirus to
      ISVPs is a prerequisite for M-cell adherence, and outer capsid proteins unique to
      ISVPs (either sigma 1 or products of mu 1) mediate interaction of virus with M
      cell apical membranes.

PMID- 7525988
TI  - Exploration of antigenic variation in gp120 from clades A through F of human
      immunodeficiency virus type 1 by using monoclonal antibodies.
AB  - The reactivities of a panel of 14 monoclonal antibodies (MAbs) with monomeric
      gp120 derived from 67 isolates of human immunodeficiency virus type 1 of clades A
      through F were assessed by using an antigen-capture enzyme-linked immunosorbent
      assay. The MAbs used were all raised against gp120 or gp120 peptides from clade B
      viruses and were directed at a range of epitopes relevant to human
      immunodeficiency virus type 1 neutralization: the V2 and V3 loops, discontinuous
      epitopes overlapping the CD4-binding site, and two other discontinuous epitopes.
      Four of the five V3 MAbs showed modest cross-reactivity within clade B but very
      limited reactivity with gp120s from other clades. These reactivity patterns are
      consistent with the known primary sequence requirements for the binding of these
      MAbs. One V3 human MAb (19b), however, was much more broadly reactive than the
      others, binding to 19 of 29 clade B and 10 of 12 clade E gp120s. The 19b epitope
      is confined to the flanks of the V3 loop, and these sequences are relatively
      conserved in clade B and E viruses. In contrast to the limited reactivity of V3
      MAbs, CD4-binding site MAbs were much more broadly reactive across clades, two of
      these MAbs (205-46-9 and 21h) being virtually pan-reactive across clades A
      through F. Another human MAb (A-32) to a discontinuous epitope was also pan
      reactive. The CD4-binding site is strongly conserved between clades; but when
      considering the epitopes near the CD4-binding site, clade D gp120 appears to be
      the most closely related to clade B and clade E appears to be the least related.
      A tentative rank order for these epitopes is B/D-A/C-E/F. V2 MAbs reacted
      sporadically within and between clades, and no clear pattern was observable.
      While results from binding assays do not predict neutralization serotypes, they
      suggest that there may be antigenic subtypes related, but not identical, to the
      genetic subtypes.

PMID- 7525990
TI  - Role of RNA in enzymatic activity of the reverse transcriptase of hepatitis B
      viruses.
AB  - The hepadnavirus reverse transcriptase is a multifunction enzyme. In addition to
      its role in DNA synthesis, the polymerase is required for RNA packaging and also
      functions as the primer for minus-strand DNA synthesis. Previously, we
      demonstrated that the protein-priming activity of the polymerase requires a viral
      RNA segment, termed epsilon, which serves as a template for the synthesis of a
      short DNA oligomer that is covalently attached to the reverse transcriptase (G.
      H. Wang and C. Seeger, J. Virol. 67:6507-6512, 1993). We now report that epsilon
      is sufficient for activation of the reverse transcriptase to prime DNA synthesis
      through the formation of a stable RNA-protein (RNP) complex. We also demonstrate
      that the binding reaction depends on sequence-specific determinants on epsilon.
      Moreover, our results indicate that two genetically separated domains of the
      reverse transcriptase are required for formation of the RNP complex. Finally, we
      show that the polymerase has a DNA polymerase activity in the absence of epsilon
      which does not depend on the protein-priming mechanism.

PMID- 7525992
TI  - Tissue ablation in benign prostatic hyperplasia with high intensity focused
      ultrasound.
AB  - In a phase I clinical trial the morphological impact and safety of high intensity
      focused ultrasound administered transrectally for tissue ablation in prostates
      from 22 patients undergoing subsequent prostatectomy were evaluated. Location and
      size of the tissue lesions correlated well with the predefined target area and
      revealed sharply delineated coagulative necrosis in all cases. Intervening
      tissues, such as the rectal wall and posterior prostate capsule, were invariably
      intact. In a subsequent phase II clinical trial the effectiveness of transrectal
      high intensity focused ultrasound as a novel minimally invasive treatment
      modality for 50 patients with symptomatic benign prostatic hyperplasia was
      determined. The maximum urinary flow rate (ml. per second) increased from 8.9 +/-
      4.1 to 12.7 +/- 6.4 at 3 months in 44 patients, 12.4 +/- 5.6 at 6 months in 33
      and 13.1 +/- 6.5 at 12 months in 20. During the same period the post-void
      residual volume (ml) decreased from 131 +/- 120 to 48 +/- 41, 59 +/- 42 and 35 +/
      30, respectively, and the American Urological Association symptom score (points)
      decreased from 24.5 +/- 4.7 to 13.3 +/- 4.4, 13.4 +/- 4.7 and 10.8 +/- 2.5,
      respectively. These data demonstrate that transrectal high intensity focused
      ultrasound is capable of inducing coagulative necrosis in the human prostate via
      a transrectal approach while preserving intervening and adjacent tissue. A 47%
      (+4.2 ml. per second) improvement in uroflowmetry and a 53% (-13.7 points)
      decrease in the American Urological Association symptom score 1 year after
      treatment clearly prove that transrectal high intensity focused ultrasound is a
      novel and safe minimally invasive treatment option for benign prostatic
      hyperplasia.

PMID- 7525991
TI  - Neutralization-resistant variants of infectious hematopoietic necrosis virus have
      altered virulence and tissue tropism.
AB  - Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus that causes an
      acute disease in salmon and trout. In this study, a correlation between changes
      in tissue tropism and specific changes in the virus genome appeared to be made by
      examining four IHNV neutralization-resistant variants (RB-1, RB-2, RB-3, and RB
      4) that had been selected with the glycoprotein (G)-specific monoclonal antibody
      RB/B5. These variants were compared with the parental strain (RB-76) for their
      virulence and pathogenicity in rainbow trout after waterborne challenge. Variants
      RB-2, RB-3, and RB-4 were only slightly attenuated and showed distributions of
      viral antigen in the livers and hematopoietic tissues of infected fish similar to
      those of the parental strain. Variant RB-1, however, was highly attenuated and
      the tissue distribution of viral antigen in RB-1-infected fish was markedly
      different, with more viral antigen in brain tissue. The sequences of the G genes
      of all four variants and RB-76 were determined. No significant changes were found
      for the slightly attenuated variants, but RB-1 G had two changes at amino acids
      78 and 218 that dramatically altered its predicted secondary structure. These
      changes are thought to be responsible for the altered tissue tropism of the
      virus. Thus, IHNV G, like that of rabies virus and vesicular stomatitis virus,
      plays an integral part in the pathogenesis of viral infection.

PMID- 7525993
TI  - Benign prostatic hyperplasia.

PMID- 7525994
TI  - Comparison of prostate specific antigen concentration versus prostate specific
      antigen density in the early detection of prostate cancer: receiver operating
      characteristic curves.
AB  - We present the results of a prospective multicenter clinical trial of nearly
      5,000 men in which prostate specific antigen (PSA) density was compared to the
      serum PSA concentration alone for early detection of prostate cancer. All men
      were evaluated with PSA and digital rectal examination. If PSA was elevated
      (greater than 4 ng./ml., Hybritech Tandem assay) or digital rectal examination
      was suspicious, transrectal ultrasound guided biopsies were recommended. Prostate
      volume was estimated by transrectal ultrasound measurements using a prolate
      ellipse volume calculation and PSA density was calculated by dividing serum PSA
      concentration by gland volume. Using a PSA density cutoff of 0.15 as recommended
      in the literature enhanced specificity but at the cost of missing half of the
      tumors. Of the organ confined neoplasms 47% were detected by a PSA of greater
      than 4.0 ng./ml. but they were missed by a PSA density of more than 0.15. PSA
      density may not be predictive for cancer because accurate estimation of
      transrectal ultrasound volume is difficult (r = 0.61 for estimated transrectal
      ultrasound volume versus pathological prostate weight). However, a relationship
      does exist among transrectal ultrasound volume, PSA and positive predictive value
      for cancer. PSA concentrations of less than 4.0 ng./ml. did not indicate a need
      for biopsy (positive predictive value 12 to 17%) unless the digital rectal
      examination findings were suspicious for cancer. A high percentage of patients
      with a PSA of more than 10 ng./ml. had cancer (30 to 75%), regardless of gland
      size. Patients with intermediate PSA concentrations (4.1 to 9.9 ng./ml.) and a
      gland size of 50 cc or less had a 35 to 51% positive predictive value, while
      those with intermediate PSA concentrations and a large gland (more than 50 cc)
      had a 15% positive predictive value. We conclude that in men with a PSA level of
      4.1 to 9.9 ng./ml., and normal digital rectal examination and transrectal
      ultrasound findings, the use of a PSA density cutoff of more than 0.15 for biopsy
      results in half of the tumors being missed. Thus, we recommend that men in this
      group undergo biopsy based upon serum PSA concentration rather than PSA density.

PMID- 7525995
TI  - Selection of optimal prostate specific antigen cutoffs for early detection of
      prostate cancer: receiver operating characteristic curves.
AB  - A prospective clinical trial of prostate cancer screening was conducted at 6
      university centers including 6,630 men 50 years old or older who underwent a
      serum prostate specific antigen (PSA) determination and digital rectal
      examination. Biopsies were performed if the PSA level was greater than 4.0
      ng./ml. (Hybritech Tandem assay) or digital rectal examination was suspicious for
      cancer. We evaluated the effect on biopsy rate and cancer detection if the cutoff
      value was shifted from 4.0 to age-specific reference ranges recommended in the
      literature. In men 50 to 59 years old with normal digital rectal examination
      findings a decrease from 4.0 to 3.5 ng./ml. would have resulted in a 45% increase
      in the number of biopsies (39 of 87) and a projected 15% increase in cancer
      detection. An increase from 4.0 to 4.5 ng./ml. in men 60 to 69 years old would
      result in 15% fewer biopsies (35 of 238) and would miss 8% of the organ confined
      tumors (2 of 25). Increasing the cutoff to 6.5 ng./ml. in men 70 years old or
      older would result in 44% fewer biopsies (70 of 159) and would miss 47% of the
      organ confined cancers (7 of 15). The number of biopsies performed for each
      cancer detected with a PSA level of greater than 4.0 ng./ml. remains constant
      across age groupings, which suggests that the cutoff of 4.0 ng./ml. does not need
      to be altered in the older men, since it is apparently unaffected by the
      simultaneously increasing prevalence of benign prostatic hyperplasia and cancer
      with age. We conclude that a serum PSA concentration of 4.0 ng./ml. should be
      used as a general guideline for biopsy in all age groups.

PMID- 7525996
TI  - Nontraumatic elevation of prostate specific antigen following cardiac surgery and
      extracorporeal cardiopulmonary bypass.
AB  - We recently treated a number of patients with markedly elevated prostate specific
      antigen (PSA) levels associated with acute urinary retention in a post-cardiac
      surgery setting. A controlled study was conducted to determine if this elevation
      is secondary to trauma from urethral catheterization or more directly associated
      with the cardiac surgery and extracorporeal bypass. In 68 patients undergoing
      cardiac surgery serum PSA levels were determined preoperatively and 12 to 18
      hours postoperatively (after urethral catheterization). The control patients were
      23 men undergoing evaluation for chest pain in the cardiac care unit. The serum
      PSA level was markedly elevated in 38 patients (56%) after cardiac surgery. In
      contrast, only 1 control patient (4.3%) had an elevated level after urethral
      catheterization (p = 0.0001). The mean post-cardiac surgery PSA concentration was
      9.14 +/- 16.08 ng./ml. (range 0.1 to 94.8) with a mean elevation of 528% (range 
      50 to 5,155%). This finding was statistically different from the mean post
      catheterization level of 1.86 +/- 2.26 ng./ml. (range 0.2 to 9.1, p = 0.034) and
      mean elevation of 6% (range -50 to 100%, p = 0.0001) in the control patients. We
      conclude that cardiac surgery and extracorporeal cardiopulmonary bypass can cause
      a marked elevation in serum PSA that appears to be unrelated to urethral
      catheterization. Presently, the etiology of this elevation is unknown, although
      PSA measurements may eventually find use as a marker for prostatic damage
      associated with acute urinary retention in the postoperative setting.

PMID- 7525997
TI  - Prostate specific antigen.

PMID- 7525998
TI  - Expression of transforming growth factor-alpha and the epidermal growth factor
      receptor in human prostate tissues.
AB  - Cells respond to certain soluble factors that bind to cell surface receptors
      possessing intrinsic tyrosine kinase activity. Overexpression of these molecules
      has been associated with tumor progression. Enhanced prostatic cancer cell growth
      in vitro has been reported in the presence of certain growth factors. To
      characterize the patterns of expression of the epidermal growth factor receptor
      (EGFr) and transforming growth factor-alpha (TGF alpha), we studied tissue from
      107 prostate specimens using immunohistochemistry. We observed that epithelial
      cells of normal (n = 4) and benign prostatic (n = 56) tissues express EGFr but
      were unreactive for TGF alpha, while stroma cells in these tissues express TGF
      alpha but not EGFr. However, coexpression of EGFr and TGF alpha was identified in
      22 of 46 prostatic adenocarcinomas studied. These results suggest that the major
      mode of action of EGFr/TGF alpha in normal and benign prostate is that of a
      paracrine or juxtacrine loop, the ligand being expressed in the stroma cells and
      the receptor in the epithelial cells. Since a subset of prostatic carcinomas
      coexpressed the ligand and the receptor in their tumor cells, it is suggested
      that an independent autocrine signaling mechanism may occur and grant a selective
      advantage for the growth of prostate cancers.

PMID- 7526000
TI  - Dithiothreitol effects on human sperm quality.
AB  - Human semen normally coagulates immediately after ejaculation and then undergoes
      liquefaction during the next 15 to 60 minutes. Incomplete seminal liquefaction
      can result in impaired sperm motility and make clinical evaluation and
      manipulation difficult. Dithiothreitol, a mucolytic agent that reduces the
      mucoprotein disulfide bonds in sputum, has been found to induce liquefaction of
      incompletely liquefied semen in vitro. We studied the effects of dithiothreitol
      on sperm motility, viability, acrosomal integrity and morphology. A semen sample
      was provided by 45 healthy, young men at the University of Arizona. Of the
      specimens 10 (22%) demonstrated incomplete liquefaction. Sperm motility and
      motion characteristics of untreated (control) semen and semen treated with
      dithiothreitol were objectively evaluated using computer assisted semen analysis.
      Sperm cell membrane integrity and mitochondrial integrity were measured by
      fluorescence microscopy using the deoxyribonucleic acid specific fluorochrome
      propidium iodide and the mitochondria specific fluorochrome rhodamine-123,
      respectively. Acrosomal integrity was determined using the fluorescent stain
      chlortetracycline. Sperm morphology was evaluated using bright field microscopy.
      For completely liquefied semen (35 cases) dithiothreitol reduced sperm motility
      (59.1 +/- 1.2% untreated versus 53.2 +/- 1.2% treated, p < 0.01) and motion
      characteristics. However, dithiothreitol had no statistically significant effect
      on motility on sperm in the group with incompletely liquefied semen (10 cases).
      Sperm cell membrane, mitochondrial and acrosomal integrity was unaffected by
      dithiothreitol regardless of liquefaction status. Dithiothreitol caused a
      significant increase in abnormally large sperm head morphology in the group with
      completely liquefied semen. The minimal effects of dithiothreitol on sperm
      motility traits and viability support its use as a possible aid in the evaluation
      and manipulation of incompletely liquefied semen.

PMID- 7525999
TI  - Abnormal flow cytometry profiles in patients with interstitial cystitis.
AB  - Flow cytometry was performed on bladder cells from patients with interstitial
      cystitis and control patients. Cells were processed in standard fashion for flow
      cytometry with propidium iodide staining and analysis was restricted to samples
      with sufficient cells for cytokeratin gating and acceptable coefficients of
      variation. Of 14 interstitial cystitis patients 4 (29%) demonstrated aneuploid
      deoxyribonucleic acid (DNA) profiles as evidenced by a discrete peak with a DNA
      index of 1.2 or greater in the cytokeratin positive population. The aneuploid
      peak accounted for up to 54% of the cytokeratin positive population in these
      samples. No such aneuploid DNA profiles were evident in specimens obtained from
      control patients. A significant DNA tetraploid population, as evidenced by a 4C
      (G2) peak greater than 20%, was observed in 6 of 14 interstitial cystitis
      patients (43%) and 8 of 11 controls (72%). Manual counting of the per cent of
      binucleated cytokeratin positive cells in the cytokeratin stained population and
      nuclear preparations of several samples for flow analysis indicate that apparent
      DNA tetraploidy in the interstitial cystitis and control patients is due to an
      abundance of binucleated cells. Aneuploid DNA profiles on barbotage specimens
      from interstitial cystitis patients may reflect a real karyotypic abnormality or
      altered chromosome complement (true aneuploidy), abnormal chromatin structure or
      abnormal cytoplasmic binding of the propidium iodide stain. This finding may
      signal an underlying abnormality of the epithelial cell population in some
      patients with the clinical diagnosis of interstitial cystitis.

PMID- 7526001
TI  - The significance of isoechoic prostatic carcinoma.
AB  - The diagnosis of prostatic carcinoma is most commonly made today by transrectal
      ultrasound guided needle biopsy. Often hypoechoic and peripheral zone lesions are
      the only areas sampled. Recently, we showed that this approach missed a quarter
      of the cancers that would be detected by a systematic biopsy technique. We term
      these missed cancers isoechoic carcinomas. We reviewed 1,549 systematic sextant
      prostate needle biopsies, of which 417 cancers were detected and subdivided into
      hypoechoic cancers (cancers detected on biopsy of a hypoechoic sector and
      isoechoic cancers (cancers found only in normal [isoechoic] peripheral zone). We
      noted in men with only isoechoic cancers that fewer biopsy cores per prostate
      revealed cancer (mean 1.6 versus 3.0, p < 0.0001) and that these men had lower
      serum prostate specific antigen levels (mean 14.4 versus 43.7, p < 0.001). The
      Gleason scores for the isoechoic and hypoechoic cancers were indistinguishable.
      The pathological staging of hypoechoic and isoechoic cancers was also similar.
      This study suggests that while isoechoic cancers are generally smaller than
      hypoechoic cancers, they do not represent low grade clinically insignificant
      carcinomas. A systematic approach to performing prostate biopsy is recommended.

PMID- 7526002
TI  - Salvage radical prostatectomy: outcome measured by serum prostate specific
      antigen levels.
AB  - We reviewed our experience with salvage radical prostatectomy for locally
      recurrent cancer in 40 patients to assess the current complication rate and the
      results using prostate specific antigen (PSA) as an indicator of treatment
      outcome and to identify better criteria for the selection of appropriate
      candidates for this operation. Most recurrent cancers were detected by digital
      rectal examination (26 patients) or increasing serum PSA levels (10). The
      operation was technically challenging, with 6 rectal injuries (15%), 2 requiring
      temporary colostomy. Serious technical complications were more common (31%) among
      the 29 patients who underwent pelvic lymphadenectomy at the time of initial
      radiotherapy than among the 11 treated with external irradiation alone (9%).
      Urinary incontinence persisted in 18 of 31 evaluable patients (58%) and was
      successfully corrected with an artificial urinary sphincter in 9. A total of 21
      patients (54%) had pathologically advanced disease (seminal vesicle invasion
      and/or lymph node metastases). Preoperative PSA levels but not clinical stage or
      biopsy grade correlated with pathological stage (p < 0.03). If the PSA was less
      than 10 ng./ml. only 15% of the patients had an advanced pathological stage,
      compared to 86% if the PSA was 10 or more. After 2 to 97 months (mean 39) 2
      patients died of metastatic prostatic cancer, 5 had distant metastases and none
      had symptomatic local recurrence. At 5 years the actuarial nonprogression rate
      measured by PSA was 55 +/- 20%. The only pretreatment factor predictive of
      progression was the serum PSA level. If the PSA was less than 10 ng./ml. the
      actuarial rate of progression was significantly lower than if the PSA was greater
      than 10 (p < 0.05). The best results were in the subset of 18 patients with
      cancer confined to the prostate or immediate periprostatic tissue: 82% had no
      progression at 5 years. Within each of these pathological stages the results of
      salvage prostatectomy were similar to those for standard radical prostatectomy in
      patients with no prior irradiation. Although technically challenging, salvage
      prostatectomy provides excellent control of radio-recurrent cancer confined to
      the prostate or immediate periprostatic tissue and is best performed before the
      preoperative PSA level increases to greater than 10 to 20 ng./ml.

PMID- 7526003
TI  - Correlation between serum prostate specific antigen levels and the volume of the
      individual glandular zones of the human prostate.
AB  - To analyze the correlation between serum prostate specific antigen (PSA) levels
      and the volume of the individual glandular zones of the human prostate, we
      examined 31 cystoprostatectomy specimens as well as 13 radical prostatectomy
      specimens with a prostate cancer volume of 0.3 cc or less, no bladder cancer
      infiltrating the prostate, no granulomas or severe inflammation, as well as no
      patient history of radiation, transurethral resection of the prostate or hormonal
      treatment. The volumes of the peripheral zone, transition zone and central zone
      were separately determined by outlining the zonal boundaries during microscopic
      examination of all slides at each level of section. PSA was measured by the Yang
      polyclonal assay. In the univariant regression analysis the correlation
      coefficients among serum PSA and transition zone, peripheral zone and central
      zone volumes were 0.934, 0.546 and 0.368, respectively, strongly suggesting that
      most PSA leakage from the prostate into the serum comes from the transition zone.
      The regression of serum PSA and transition zone volumes leads to a prediction of
      approximately 0.261 ng./ml. PSA per gm. benign prostatic hyperplasia (BPH) plus
      an intercept of 0.878, a number in keeping with our 1987 estimates of 0.3
      ng./ml./gm. BPH. The volumes of the 3 zones appeared to be independent variables.
      Transition zone volume showed the greatest variation because of BPH. The mean
      average ratio of peripheral zone volume to central zone volume was nearly 3:1.
      These data strongly support the concept of age-adjusted PSA levels, since most of
      the increase in size of the prostate with increasing patient age comes from the
      transition zone from which BPH develops.

PMID- 7526004
TI  - Localization of nitric oxide synthase in spinal nuclei innervating pelvic
      ganglia.
AB  - We employed retrograde axonal tracing techniques and nitric oxide synthase (NOS)
      and choline acetyltransferase (ChAT) immunohistochemistry to identify NOS
      containing neuronal populations within the lumbosacral spinal cord and determine
      whether these project to the major pelvic ganglion in the adult male Sprague
      Dawley rat. Immunohistochemical localizations of NOS included neurons situated at
      the L5 to S2 segments of the spinal cord, which corresponded to the sacral
      parasympathetic nucleus. Another prominent locus for NOS was a group of neurons
      identified in the L1 segment corresponding to the dorsal commissural nucleus.
      These regions correlated directly with preganglionic parasympathetic and
      sympathetic neuronal origins, respectively, which were established with ChAT
      colocalizations. Retrograde tracing verified the projection of these neurons to
      the pelvis. Additional neuronal localizations of NOS were observed throughout the
      intermediolateral cell column, involving the superficial laminae of the dorsal
      horn, in the region surrounding the central canal and occasionally in the medial
      area of the ventral horn. These results indicate that the regulation of pelvic
      visceral activity may involve NO-based neuronal mechanisms operating at the level
      of the lumbosarcal spinal cord.

PMID- 7526005
TI  - Immunohistochemical staining of ras p21: staining in benign and malignant
      prostate tissue.
AB  - A total of 124 specimens of prostate tissue (25 normal prostate, 41 benign
      prostatic hyperplasia, 58 adenocarcinoma) was immunostained for ras p21 using a
      commercially available monoclonal antibody directed against a peptide sequence
      conserved among all members of the ras gene family. Of normal prostate specimens,
      76% showed no staining while the remainder showed only weak epithelial
      (glandular) staining. No significant stromal staining was noted in any normal
      prostate specimen. In contrast most benign prostatic hyperplasia specimens showed
      abundant staining. Epithelial staining was observed in 88% and stromal staining
      in 73% of specimens. A majority of prostate carcinoma specimens also stained,
      with 62% and 36% showing epithelial and stromal staining, respectively. No
      association was noted between staining and either tumor grade or clinical stage.
      These data argue against any clinical usefulness of immunostaining for ras p21 in
      the diagnosis or grading of prostate cancer.

PMID- 7526006
TI  - Comparative study of laser versus electrocautery prostatic resection: 18-month
      followup with complex urodynamic assessment.
AB  - A total of 25 patients with symptomatic bladder outlet obstruction due to benign
      prostatic hyperplasia was entered into a prospective, randomized trial comparing
      prostatectomy done with the Urolase right angle firing neodymium:YAG laser fiber
      and standard transurethral electroresection of the prostate. Efficacy of
      treatment, as assessed by standardized American Urological Association symptom
      scores, patient assessment of symptom improvement, peak urinary flow rates, post
      void residual urine volumes and complex urodynamic evaluation, including
      assessment of opening pressure and maximum detrusor voiding pressure, was
      equivalent for the 2 treatment groups through 1 year. Ultrasonic assessment of
      prostatic volumes at 1 year showed a mean decrease in total volume of 59% for
      standard electrocautery resection compared to 28% for laser prostatectomy.
      Symptom scores and peak urinary flow rates remained equivalent for both groups
      through 18 months.

PMID- 7526007
TI  - Using repeated measures of symptom score, uroflowmetry and prostate specific
      antigen in the clinical management of prostate disease. Benign Prostatic
      Hyperplasia Treatment Outcomes Study Group.
AB  - Measurements of American Urological Association symptom score, peak urine flow
      rate and prostate specific antigen (PSA) are often followed over time in
      urological management. However, their interpretation is confounded by within
      patient variability due to chance. Data from 2 clinical trials are used to
      examine the magnitude of this variation. When these measures are repeated at a
      short interval variation is modest and might easily be misinterpreted as a true
      change in patient condition. For example, approximately 20% of patients might be
      expected to have a chance increase or decrease in symptom score by at least 4.9
      points, in peak urine flow rate by at least 4.1 ml. per second or in PSA by at
      least 1.6 ng./ml. Clinicians can use these data to help interpret repeated
      measures of these variables in patients, and can consider obtaining paired
      measurements to decrease the effect of chance variation when they plan on
      following them over time.

PMID- 7526008
TI  - Chronic changes in blood flow alter endothelium-dependent responses in autogenous
      vein grafts in dogs.
AB  - PURPOSE: Experiments were designed to determine the effects of blood flow on
      endothelium-dependent relaxations in canine vein grafts. METHODS: Blood flow
      through reversed femoral vein grafts was either increased by a distal
      arteriovenous fistula (increased flow), unmanipulated (normal flow), or reduced
      by a proximal adjustable clamp (reduced flow). Six weeks after implantation,
      blood flow through the graft was measured. Rings cut from grafts were suspended
      for the measurement of isometric force in organ chambers to determine endothelial
      function. RESULTS: Blood flow was significantly greater in grafts with a distal
      fistula compared to grafts with normal or decreased flow. Endothelium-dependent
      relaxations to acetylcholine were absent in all grafts. Endothelium-dependent
      relaxations to adenosine diphosphate, thrombin, and the calcium ionophore A23187
      were less in grafts with reduced flow compared with grafts with increased flow.
      Relaxations to these agents in grafts with increased flow were reduced by an
      analog of L-arginine. Neointimal hyperplasia was increased in grafts with reduced
      flow. CONCLUSIONS: These data demonstrate that chronic diminution of blood flow
      decreases receptor-mediated release of endothelium-derived relaxing factors and
      increases neointimal hyperplasia in canine vein grafts. The production of
      endothelium-derived relaxing factors, one of which is nitric oxide, may influence
      the development of myointimal hyperplasia in vein grafts.

PMID- 7526009
TI  - Cellular localization of matrix metalloproteinases in the abdominal aortic
      aneurysm wall.
AB  - PURPOSE: This study explores the source(s) of the matrix-degrading proteinases,
      matrix metalloproteinase 1 (MMP-1; interstitial collagenase), matrix
      metalloproteinase 3 (MMP-3; stromelysin 1), and matrix metalloproteinase 9 (MMP
      9; gelatinase B), previously implicated in abdominal aortic aneurysm (AAA)
      development. The possible involvement of the plasmin cascade in the activation of
      these proteinases was also explored by examining the presence of the urokinase
      type plasminogen activator (uPA) in aneurysm wall. METHODS: Immunohistochemical
      techniques were used to detect the presence of MMP-1, MMP-3 and MMP-9 proteins
      and uPA in fixed, paraffin-embedded tissue sections from AAA (n = 10) and control
      (n = 2) aortas. RESULTS: The MMP-9 protein was localized to mononuclear cells in
      the AAA wall. Dual-labeling techniques confirmed the identity of these cells as
      macrophages. The MMP-3 protein and uPA were also detected primarily in the
      macrophage-like mononuclear cells infiltrating the aneurysmal aorta.
      Immunoreactive material to MMP-1 was demonstrated in mesenchymal cells of the AAA
      wall suggesting alternative expression and delivery of this enzyme in AAA.
      CONCLUSIONS: This work establishes the role of macrophages in the delivery,
      expression, and possible activation of matrix destructive proteinases during AAA
      pathogenesis and suggests a role for the activation of MMPs in the progression of
      the disease.

PMID- 7526010
TI  - The attempted assassination of President Reagan. Medical implications and
      historical perspective.
AB  - In 1981, President Ronald Reagan became the first incumbent president of the
      United States to survive being struck by a would-be assassin's bullet. Had
      President Reagan not survived, the history of this country and the world most
      certainly would have been changed. This report is the only first-hand account of
      the details of his medical care and complications following the assassination
      attempt, an event that emphasizes the vulnerability of presidents to would-be
      assassins and the importance of readily available expert medical care and
      facilities to their survival.

PMID- 7526011
TI  - [Recent advance in cardiovascular regulation research].

PMID- 7526013
TI  - [Roles of cell-adhesion molecules in myocardial reperfusion injury].

PMID- 7526012
TI  - [Regulatory mechanisms of endothelial nitric oxide synthase activity and its
      modification by lipids and cytokines].

PMID- 7526017
TI  - Sequential changes in stem cell markers in peripheral blood and leukapheresis
      samples after injections of recombinant human granulocyte colony-stimulating
      factor in patients with urogenital malignant solid tumors: a preliminary study.
AB  - In order to evaluate the mobilization effect of recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) on peripheral blood stem cells (PBSCs), rhG
      CSF was given to patients with urogenital malignancy before chemotherapy. Markers
      for the stem cells, such as colony forming unit-granulocyte/macrophage (CFU-GM)
      and burst forming unit-erythrocyte (BFU-E), were sequentially monitored in
      peripheral blood and leukapheresis samples. Five patients, including a 13-year
      old boy, were given 5 micrograms/kg rhG-CSF subcutaneously: the pediatric case
      for four consecutive days and the adult cases for six consecutive days (53-72
      years of age). None of the patients had received chemotherapy within the four
      weeks prior to the start of the rhG-CSF series. PBSC collections were performed
      on the fifth day in the pediatric case and on the fifth and seventh days in the
      adult cases. Progenitor cells were monitored by methyl-cellulose cell culture
      techniques. CFU-GM on day 5 of the rhG-CSF series in peripheral blood increased
      14- to 53-fold compared with samples taken immediately before the series. CFU-GM
      in the leukapheresis products on day 5 was greatest (70 x 10(3)/kg) in the
      pediatric case and least (14 x 10(3)/kg) in the oldest patient's case. The totals
      of the CFU-GM collected by two phereses in the adult cases were 21-73 x 10(3)/kg
      and the totals of CD34 positive cells were 0.6 to 1.4 x 10(6)/kg. The data
      suggest rhG-CSF to induce sufficient PBSCs for bone marrow rescue into the
      peripheral blood without any preceding chemotherapy. The patient's age may,
      however, be a contributory factor in using this method.

PMID- 7526016
TI  - Preliminary evaluation of the new tumor marker, CYFRA 21-1, in lung cancer
      patients.
AB  - Serum samples from 137 lung cancer patients were examined by RIA to evaluate the
      clinical efficacy of the new tumor marker, CYFRA 21-1, which could identify the
      soluble fragment of cytokeratin 19. The cut-off value was determined to be 2.2
      ng/ml according to the receiver operating characteristic curve. The sensitivity,
      specificity and accuracy of the RIA for CYFRA 21-1 were 57.7, 91.9 and 64.9%,
      respectively. The serum concentration of CYFRA 21-1 and the sensitivity of the
      assay increased as the disease progressed. Histologically, the sensitivity was
      highest for squamous cell carcinomas (SQ) (76.5%) in comparison with
      adenocarcinomas (47.8%) and small cell lung cancers (42.1%) (P < 0.01, P < 0.05,
      respectively). The sensitivities for SQ were 60.0, 83.3, 80.0 and 100% at stages
      I, II, III and IV, respectively. When compared with CEA (45.3%) and squamous cell
      carcinoma related antigen (SCC) (22.6%) in all lung carcinomas, CYFRA 21-1 showed
      the highest sensitivity (57.7%), (P < 0.05, P < 0.01, respectively). In SQ, the
      sensitivity of the CYFRA 21-1 RIA was significantly higher than that of the assay
      for SCC (47.1%) (P < 0.05). In patients with adenocarcinomas, the sensitivity of
      the CYFRA 21-1 assay was almost the same as that for CEA (49.3%). In a
      combination of CYFRA 21-1 and CEA for non-small cell lung cancers (NSCLC), the
      sensitivity and accuracy increased to 75.4 and 78.1%, respectively, although the
      specificity decreased to 86.5%. It is concluded that CYFRA 21-1 could replace
      SCC, a less satisfactory tumor marker, for SQ of the lung. The potentiality of
      the combination of CYFRA 21-1 and CEA for NSCLC should be estimated using larger
      samples in the near future.

PMID- 7526019
TI  - Recent advances in biomedical sciences of Burkholderia pseudomallei (basonym:
      Pseudomonas pseudomallei).

PMID- 7526014
TI  - Effects of microsphere suspension agents on systemic hemodynamics in rats.
      Comparison of nonradioactive colored and radioactive microspheres.
AB  - The systemic hemodynamic effects of different microsphere suspension agents were
      evaluated in 22 Sprague-Dawley male rats. Rats were divided into three groups,
      and three different solutions (distilled water; n = 7, 10% dextran; n = 8, and
      70% glucose; n = 7) were injected through the left atrium respectively. 0.2 ml of
      each solution was injected repeatedly until significant hemodynamic changes
      developed. During four sequential injections, distilled water had no significant
      effects on cardiac output, mean arterial pressure, and heart rate. However, the
      10% dextran (mol wt 70,000) solution produced significant decreases in both
      cardiac output and mean arterial blood pressure during and after the third
      injection. The 70% glucose solution also decreased, cardiac output significantly
      during the third injection. Although microspheres itself must cause some
      hemodynamic changes, our results indicated that the hemodynamic disturbances
      observed during a large dose injection of microspheres might have been at least
      in part due to the use of high-density suspending solutions. The doses of
      radioactive microsphere solution in many previous rat studies were usually less
      than 0.6 ml. However, in the case of large dose injection of microspheres, these
      results indicate that the suspending solutions can affect hemodynamic parameters
      in various ways.

PMID- 7526015
TI  - [Chronic cold agglutinin disease accompanied with an increase of CD20+/CD5+
      cells; a case report].
AB  - A 61-year-old male complained of acrocyanosis and dark urine when exposing to
      cold temperatures. This had continued for several years. His physical
      examinations showed neither lymphadenopathy nor hepatosplenomegaly. Laboratory
      findings were as follows; RBC 305 x 10(4)/microliters, Hb 10.3 g/dl,
      reticulocytes 4.32%, platelets 27.3 x 10(4)/microliters, WBC 7,400/microliters
      with 50% lymphocytes, and a high cold agglutinin titer (2,048-fold) with anti-I
      specificity. Bone marrow smear preparations showed erythroid hyperplasia and
      increase of lymphocytes (52%). Immunophenotypic analysis showed an increase of
      CD20+/B-lymphocytes in peripheral blood (32.6%) and in bone marrow, and 94% of
      these cells co-expressed CD5. Most B-lymphocytes expressed surface IgM-lambda,
      suggesting a monoclonal proliferation of B-lymphocytes. At this point we
      diagnosed cold agglutinin disease (CAD) because there was no evidence of
      lymphoma, and the absolute number of peripheral blood lymphocytes was lower than
      the criteria of chronic lymphocytic leukemia (CLL) proposed by the International
      Workshop (1989). However, there still remains the possibility of the transitional
      form between "idiopathic" CAD and B-CLL or lymphoma.

PMID- 7526018
TI  - [Adsorption of acid or basic dyes by asbestos].

PMID- 7526023
TI  - [Thrombocyte aggregation in patients with cardiac arrhythmias and effect of anti
      arrhythmia agents].
AB  - Platelet aggregability was studied in 81 patients with prior myocardial
      infarction with various cardiac arrhythmias and its effects of some
      antiarrhythmic agents (allapinine, ethacizine, obsidan and cordarone). It was 32
      39% higher in patients with frequent ventricular extrasystole (VE) and VE of high
      grades (4a and 4b by the classification of Lown and Wolt) than in control
      patients (without arrhythmias) and patients with supraventricular and rare VE.
      Ethacizine and cordarone produced a significant inhibitory effects on platelet
      functional activity, but the effects of allapinine and obsidan on this parameter
      were insignificant. There was no correlation between the magnitude of
      antiarrhythmic effects of the drugs and their antiaggregatory properties. It was
      shown that the results of examining the effects of antiarrhythmic agents on
      platelet aggregability in vitro were not in agreement with those obtained in
      vivo.

PMID- 7526022
TI  - [Commemorative lecture of receiving Imamura Memorial Prize. II. Mode of action of
      oligonucleotide fraction extracted from Mycobacterium bovis BCG].
AB  - A fraction extracted from Mycobacterium bovis BCG was found to exhibit strong
      antitumor activity. This fraction, which was designated MY-1, caused some animal
      tumors to regress and/or prevent metastasis very effectively. MY-1 after
      digestion with DNase had almost completely reduced activity, while MY-1 digested
      with RNase did not. MY-1 also augmented natural killer (NK) cell activity of
      mouse spleen cells in vitro, and produced factors which showed anti-viral
      activity and rendered macrophages cytotoxic towards tumor cells. The function of
      the factor to activate macrophages was destroyed by treatment with anti
      interferon (IFN)-gamma antibody, while the anti-viral activity was destroyed by
      treatment with anti-INF alpha/beta antibody. The oligonucleotides contained in MY
      1 distributed in a broad range of molecular size, and peaked at 45 nucleotides.
      We synthesized 13 kinds of 45-mer nucleotides with sequence present in the known
      cDNA encoding various BCG proteins. Six out of these oligonucleotides, which
      contained one or more hexameric palindromic structures, showed strong antitumor
      activity, while the other without palindrome did not. These active
      oligonucleotides possessed the capability to induce IFN and to augment NK cell
      activity of mouse spleen cells by coincubation in vitro. When a portion of the
      sequence of the inactive oligonucleotides was substituted with either palindromic
      sequence of GACGTC, AGCGCT or AACGTT, the oligonucleotide acquired the ability to
      augment NK activity. In contrast, the oligonucleotides substituted with another
      palindromic sequence such as ACCGGT was without effect. Furthermore, exchange of
      two neighboring mononucleotides within, but not outside, the active palindromic
      sequence destroyed the ability of the oligonucleotide to augment NK
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526020
TI  - Acetoside, a component of Stachys sieboldii MIQ, may be a promising antinephritic
      agent: effect of acteoside on crescentic-type anti-GBM nephritis in rats.
AB  - Effects of acetoside (ACT) on crescentic-type anti-GBM nephritis in rats were
      investigated. When rats were treated with ACT from the 1st day after i.v.
      injection of anti-GBM serum, ACT inhibited the elevation of protein excretion
      into urine. In the ACT-treated rats, cholesterol and creatinine contents and
      antibody production against rabbit gamma-globulin in the plasmas were lower than
      those of the nephritic control rats. Histological observation demonstrated that
      this agent suppressed hypercellularity and the incidence of crescent formation,
      adhesion of capillary wall to Bowman's capsule and fibrinoid necrosis in the
      glomeruli. Furthermore, rat-IgG and C3 deposits on the GBM were significantly
      less in the ACT-treated group than in the control nephritic group. When the
      treatment was started from the 20th day after i.v. injection of anti-GBM serum,
      by which the disease had been established, ACT resulted in a similar effect on
      the nephritic rats as stated above. These results suggest that ACT may be a
      useful medicine against rapidly progressive glomerulonephritis, which is
      characterized by severe glomerular lesions with diffuse crescents.

PMID- 7526024
TI  - C5b-9 increases albumin permeability of isolated glomeruli in vitro.
AB  - Deposition of antibody and activation of the complement cascade are important in
      both naturally occurring glomerulonephritis and in experimental models including
      passive Heymann nephritis. We studied the effect of antibody and complement on
      albumin permeability of isolated glomeruli to determine the role of the terminal
      complement components (C5-C9) in mediating the proteinuria in nephritis. Isolated
      glomeruli were treated with anti-Fx1a (Heymann antibody) and then incubated them
      with pooled human serum, serum in which complement had been inactivated by heat,
      or serum deficient in C6 or C7. The albumin reflection coefficient (sigma
      albumin) was calculated from the volumetric response of glomeruli to
      transcapillary oncotic gradients produced by albumin or high molecular weight
      neutral dextran (252 kD). Convectional permeability to albumin (Palbumin) was
      calculated as 1-sigma albumin. Albumin permeability of control glomeruli was not
      different from 0. Albumin permeability was not altered by antibody alone but was
      increased to 0.65 +/- 0.04 when antibody treated glomeruli were incubated for 10
      minutes with pooled serum as a source of complement. Heat treatment of serum to
      inactivate complement prevented the increase in permeability. Incubation for 10
      minutes with serum without antibody pretreatment caused a lesser increase in
      permeability of isolated glomeruli (0.18 +/- 0.06). Serum deficient in either C6
      or C7 did not cause an increase in albumin permeability of antibody pre-treated
      glomeruli, but incubation with a combination of these sera (now containing the
      complete cascade) increased permeability to the same extent as did pooled normal
      serum (0.58 +/- 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526026
TI  - [Current aspects of postoperative thrombophlebitis and pulmonary artery
      thromboembolism].
AB  - From analysis of clinical material of more than 1,000 patients with surgical
      diseases of the abdominal organs obtained by modern examination methods and
      processing developed by the author, including diagnostic, prognostic, and
      preventive procedures and methods, and from the results of pathopharmacological
      study of the venous bed in 500 patients who died in the early postoperative
      period, the main aspects of postoperative phlebothrombosis and thromboembolism of
      the pulmonary arteries were studied: their frequency, localization, early
      diagnosis, dynamics of changes, dependence on some risk factors, etc. The
      decisive rule of individual preoperative prognostication of postoperative venous
      thrombosis was developed and tested in the surgical clinic with 76% statistical
      significance. The use of the processing developed by the author reduced the
      incidence of postoperative thromboembolic complications in various groups of risk
      by 5-36 times and did not cause increased bleeding of the wound.

PMID- 7526021
TI  - [A cooperative study on the incidence of bacteriuria in patients with benign
      prostatic hypertrophy].
AB  - The incidence of bacteriuria in patients with benign prostatic hypertrophy was
      studied at 8 National Hospitals. Among 1,542 patients, urinary infection was the
      reason of visit in 63 patients (4.1%). After open and transurethral
      prostatectomy, one-third of patients developed bacteriuria (30 of 59 subcapsular
      enucleations, and 252 of 776 transurethral resections). When a catheter is placed
      without prophylactic antimicrobial, all patients developed bacteriuria within 10
      days, and within 30 days even if they received antimicrobials. The incidence of
      bacteriuria increased with age.

PMID- 7526025
TI  - Platelet-leukocyte aggregation during hemodialysis.
AB  - Hemodialysis is associated with simultaneous changes in leukocytes and platelets,
      but it is unclear whether these alterations affect the interactions between these
      cell types. To evaluate this process, we examined the appearance of platelet
      specific antigens (CD41) on leukocytes as an index of platelet-leukocyte
      aggregation during hemodialysis using three different synthetic membranes.
      Patients with end-stage renal disease (ESRD) on long-term hemodialysis treatment
      were enrolled. Flow cytometric techniques and platelet specific monoclonal
      antibodies (MoAb) that recognize the glycoprotein complex on resting and
      activated platelets (anti-CD41), the activated GPIIb-IIIa complex receptor (anti
      LIBS1), and the p selectin GMP140, that is exposed on platelet plasma membrane
      after activation and platelet degranulation (anti-CD62), were used. Subjects with
      ESRD had a lower predialysis platelet surface expression of CD41 and LIBS1
      compared to normal controls, but unchanged CD62 expression. In parallel, patients
      with ESRD manifested a uniformly reduced platelet-leukocyte microaggregates
      predialysis compared to normal controls. When examined across the dialyzer,
      however, an increase in platelet-neutrophil and platelet-monocyte microaggregates
      was observed with all three synthetic membranes at both 15 and 30 minutes after
      initiation of dialysis. This phenomenon could be duplicated in vitro by
      physiologic concentrations of the platelet specific agonist ADP, but not by the
      complement factors C3a or C5a. We conclude that platelet-leukocyte aggregates
      occur during dialysis likely related to a primary platelet activation mechanism.
      This phenomenon may serve as a new biocompatibility parameter and may shed light
      on some of the biologic consequences of hemodialysis.

PMID- 7526027
TI  - [Concept and interim result of the ALL-BFM 90 therapy study in treatment of acute
      lymphoblastic leukemia in children and adolescents: the significance of initial
      therapy response in blood and bone marrow].
AB  - In the ongoing trial ALL-BFM 90 for the treatment of childhood non-B cell acute
      lymphoblastic leukemia (ALL) 1468 unselected patients (pts) were enrolled from 84
      centers in Germany and Switzerland from 4/90 to 12/93. Based on the results of
      the previous trial ALL/NHL-BFM 86 this treatment program focused especially on
      therapy modifications for average (MRG) and high risk (HRG) pts, on the
      evaluation of therapy response for prognosis, and on the identification of high
      risk pts by molecular genetics. For average risk pts consolidation therapy was
      intensified by the addition of L-asparaginase (L-ASP) on a randomized basis. In
      HRG induction and consolidation therapy was modified by introduction of early
      intensification elements that had proved to be effective in relapsed pts. This
      patient group was randomized for the evaluation of the effects of G-CSF
      administered in the intervals between the intensification elements. Distribution
      of the 1376 eligible pts into the three treatment arms SRG (standard risk), MRG,
      and HRG was as expected (17 pts not yet assigned): 385 pts (28.0%), 834 pts
      (60.6%), and 140 pts (10.2%), respectively. Treatment consisted of the 8-drug
      induction (Protocol I), consolidation (Protocol M), reinduction (Protocol II),
      and maintenance therapy (total therapy duration 24 months). The drug doses and
      combinations were only slightly modified compared to the previous study ALL-BFM
      86 with the exception of the randomized L-ASP containing arm MRG-2 (Protocol M-A)
      and group HRG. Preventive cranial irradiation was reduced to 12 Gy and applied to
      MRG and HRG pts only. As in study ALL-BFM 86, the initial response to a 7-day
      exposure to prednisone and to the first intrathecal injection of MTX at diagnosis
      was evaluated at day 8 of treatment with regard to blast count in peripheral
      blood (PB). In addition, pts were now investigated for the presence of blasts in
      the bone marrow (BM) at day 15 of treatment to compare the prognostic power of
      both response parameters. Identification of translocation t(9; 22) and/or BCR-ABL
      rearrangement characterized a small subgroup of pts that were not detected by
      poor initial therapy response. These pts were enrolled in HRG for more intensive
      treatment including allogeneic bone marrow transplantation (BMT). After a median
      observation time of 22 months, the overall probability for event-free survival (p
      EFS) is 82 +/- 2%. 11 pts (0.8%) died before complete remission (CR) was
      achieved, 15 pts (1.1%) died while in CR for reasons other than relapse.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7526029
TI  - Inhibitory effect of FK506 on intercellular adhesion molecule-1 (ICAM-1)
      expression on cultured thyroid cells.
AB  - The effect of FK506, an immunosuppressive agent, on phytohemagglutinin (PHA) or
      interferon gamma (IFN gamma)-induced intercellular adhesion molecule-1 (ICAM-1)
      expression on cultured human thyroid cells from patients with Graves' disease was
      investigated. Primary cultured thyroid cells were incubated for three days with
      IFN gamma (10 to 800 U/ml) or PHA (1 to 50 micrograms/ml) in the presence of
      FK506. The surface expression of ICAM-1 was measured by flow cytometry. In some
      experiments, polyclonal anti-IFN gamma antibody was added to the culture to
      determine whether ICAM-1 expression was blocked. FK506 inhibited the PHA-induced
      ICAM-1 expression in thyroid cells, but not the induction by IFN gamma. PHA
      induced ICAM-1 expression was not inhibited by the polyclonal anti-IFN gamma
      antibody. FK506 did not affect the proliferation of thyroid cells. This data
      indicates that the inhibitory effect of FK506 on ICAM-1 expression in primary
      cultured thyroid cells may be due to actions on infiltrating lymphocytes in the
      thyroid gland. Further studies are necessary to elucidate whether the inhibition
      of ICAM-1 by FK506 results in the suppression of autoimmune reactions in the
      thyroid gland.

PMID- 7526030
TI  - Oxalate nephrosis in Macaca fascicularis.
AB  - Crystals within the renal proximal convoluted tubules of several cynomolgus
      monkeys (Macaca fasciculata) were investigated by light and scanning electron
      microscopy together with histochemistry and X-ray microanalysis techniques. The
      crystals were shown to have the physical structure and staining characteristics
      of calcium oxalate monohydrate. The incidence varied between different batches of
      animals and no definite cause was established.

PMID- 7526028
TI  - [Results of the HB-89 Study in treatment of malignant epithelial liver tumors in
      childhood and concept of a new HB-94 protocol].
AB  - 94 children with a primary liver neoplasm were registered in the Cooperative
      Pediatric Liver Tumor Study HB-89 of the GPOH from 1988 to 1992. 64 of these had
      a hepatoblastoma (HB), 12 a hepatocellular carcinoma (HCC), 2 a sarcoma and 16 a
      benign tumor. 51 (80%) patients with an HB were 6 to 36 months of age, 9 with an
      HCC above 10 years. Initial serum-alpha-fetoprotein (AFP) was elevated in 51 HB
      patients and exceeded the 3-fold of normal range in 45. Children with low (< 100
      ng/ml) and very high (> 1,000,000 ng/ml) levels had a significantly worse
      prognosis than those with intermediate values (p = 0.0014). AFP was moderately
      elevated in 9 HCC patients. All other tumor markers were only irregularly above
      normal range. 48 (77%) of HB patients survived, 45 (73%) are tumor free. All of
      18 stage I and 4/5 stage II patients are in remission. After chemotherapy 30/36
      stage III HBs and 2/5 stage IV HBs could be resected, 9 of these patients
      suffered from tumor relapse. Disease-free survival was 100% for stage I, 80% for
      stage II, 68% for stage III and zero for stage IV HB (p = 0.0005). Surgical
      complications occurred after 8% of biopsies, 13% of limited primary resections
      and 25% of extended secondary resections. There was no perioperative death. The
      completeness of tumor resection at primary or delayed surgery correlated
      significantly with patients disease-free survival (p < 0.0001). Chemotherapy with
      ifosfamide, cisplatin and adriamycin was effective in HB. 203 courses were given
      in 61 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526031
TI  - Phytanic acid alpha-oxidase deficiency (Refsum disease) presenting in infancy.
AB  - This report describes a patient with high serum phytanic acid concentration due
      to phytanic acid alpha-oxidase deficiency (classical Refsum disease). He
      presented unusually early, hypotonia and developmental delay being apparent by 7
      months. A generalized peroxisomal disorder (so-called 'infantile Refsum disease')
      was excluded by analyses of pristanic acid, very long-chain fatty acids, bile
      acids and plasmalogen synthesis. The early presentation raises the possibility of
      in utero exposure to phytanate.

PMID- 7526032
TI  - Propionic acidaemia and immunodeficiency.

PMID- 7526033
TI  - Cellular and hormonal mechanisms associated with malignant bone resorption.
AB  - BACKGROUND: To obtain a better understanding of the cellular and hormonal
      mechanisms responsible for the malignant bone resorption associated with
      metastatic carcinoma, we sought to identify whether tumor cells or tumor
      infiltrating macrophages were capable of lacunar bone resorption. EXPERIMENTAL
      DESIGN: Tumor cells and tumor-infiltrating macrophages (TIMS), (nonspecific
      esterase and F4/80 positive: cytokeratin and tartrate-resistant acid phosphatase
      and calcitonin response negative), were isolated from carcinomas that developed
      after subcutaneous implantation of human breast, colon, and cervical carcinoma
      cell lines into MFI athymic nude mice. These cells were cultured alone or with
      stromal cells on bone slices and evidence of lacunar resorption sought by
      scanning electron microscopy. RESULTS: After 7 to 14 days in co-culture with
      UMR106 osteoblast-like cells in the presence of 1,25-dihydroxy vitamin D3, only
      cells of the TIM population differentiated into osteoclast-like cells
      (nonspecific esterase-negative: tartrate-resistant acid phosphatase-positive)
      capable of extensive lacunar bone resorption. CONCLUSIONS: Cells within the TIM
      population but not tumor cells are capable of differentiation into osteoclast
      like cells which can resorb bone extensively. Both 1,25 dihydroxyvitamin D3 and
      bone stromal cells are necessary for this to occur. TIM differentiation into
      cells capable of lacunar resorption could account for a component of the
      extensive osteolysis associated with carcinomatous skeletal metastases.

PMID- 7526035
TI  - Localization of pregnancy-associated plasma protein-A and colocalization of
      pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil
      granule major basic protein messenger ribonucleic acid in placenta.
AB  - BACKGROUND: The human eosinophil granule major basic protein (MBP), a 13.8
      kilodalton cationic polypeptide constituting the core of the eosinophil granule,
      is cytotoxic to parasites and numerous mammalian cells. Concentrations of a
      molecule immunochemically similar to eosinophil granule MBP are present in
      maternal plasma, and MBP mRNA has been localized to placental X cells by in situ
      hybridization. Eosinophil granule MBP is initially translated as a nontoxic
      precursor (proMBP), containing a 9.9 kilodalton acidic pro-portion that is
      believed to neutralize MBP toxicity. Recent analyses of sera from pregnant women
      have revealed that pregnancy-associated plasma protein-A (PAPP-A), previously
      thought to be a homotetramer of PAPP-A subunits, is actually composed of PAPP-A
      subunits bound by disulfide bonds to equimolar amounts of proMBP molecules to
      form a complex, PAPP-A/proMBP. In addition, the PAPP-A subunit nucleotide and
      deduced amino acid sequence have been determined from cloned cDNA. The PAPP-A
      monomer found in plasma contains 1547 amino acid residues. EXPERIMENTAL DESIGN:
      Because of the new evidence that PAPP-A is complexed with proMBP, previous
      studies on the localization of PAPP-A using antibodies to PAPP-A must be
      questioned. To determine the localization of the PAPP-A subunit,
      immunofluorescence was performed on normal placental tissues using proMBP
      absorbed anti-PAPP-A antibody. Furthermore, the expression of PAPP-A mRNA was
      investigated by in situ hybridization. RESULTS: Immunofluorescence staining with
      proMBP absorbed anti-PAPP-A antibody showed that PAPP-A is localized to placental
      septa, anchoring villi, and the syncytia of chorionic villi, whereas MBP is
      localized only to septa and anchoring villi. By in situ hybridization, PAPP-A
      mRNA is detected in placental X cells and syncytiotrophoblasts, but MBP mRNA is
      localized only to placental X cells. CONCLUSIONS: The presence of PAPP-A mRNA and
      PAPP-A subunit protein in placental X cells and syncytiotrophoblasts indicates
      that both X cells and syncytiotrophoblasts synthesize the PAPP-A subunit, whereas
      only X cells synthesize proMBP.

PMID- 7526034
TI  - Characterization of a spontaneously transformed human endothelial cell line.
AB  - BACKGROUND: A line of cells was isolated from a focus observed in a human
      umbilical vein endothelial cell (HUVEC) culture, presumably the result of a
      spontaneous transformation event. EXPERIMENTAL DESIGN: The cell line was
      continuously cultured for 16 months, after which time, the proliferative rate,
      capacity to be cloned, and ability to be transfected was investigated. The cell
      line was analyzed for expression of endothelial cell markers, von Willebrand
      Factor, P selectin, and scavenger receptor. We also examined the tumor necrosis
      factor (TNF)-mediated upregulation of E-selectin, vascular cell adhesion molecule
      1 and intercellular adhesion molecule-1. We evaluated the levels of expression
      and types of TNF-alpha receptor expressed by the cell line, and the cell lines
      response to interleukin-4 and interferon-gamma. CD34 expression of this cell line
      and the ability of transforming growth factor-beta to inhibit the TNF-alpha
      induction of E-selectin was examined. The ability to support neutrophil adhesion
      and transmigration, and generate capillary-like tubes in vitro was assessed.
      Finally, the karyotype and tumourigenicity of this line was established. RESULTS:
      This cell line (C11STH) has a doubling time comparable to that of normal HUVECs
      and has a trisomy of chromosome 8 and 11. The cell line is capable of generating
      colonies at clonal density, and is transfectable with efficiencies comparable to
      normal HUVECs. C11STH expresses von Willebrand factor, P-selectin, and scavenger
      receptor to an extent similar to passaged HUVECs and can be induced to express E
      selectin, VCAM, and ICAM with TNF-alpha. C11STH expresses both the p55 and p75
      subunits of TNF-alpha receptor at levels similar to HUVECs. The ability of
      interleukin-4 to enhance the expression of VCAM and reduce the TNF-alpha-mediated
      expression of E-selectin is maintained in this cell line. C11STH cells are unable
      to induce class II major histocompatibility antigen in response to interferon
      gamma. However, interferon-gamma is able to synergize with TNF to enhance the
      expression of E-selectin. C11STH cells do not express CD34 or show transforming
      growth factor-beta inhibition of TNF-alpha induced E-selectin expression,
      functions indicative of primary, or early passage HUVECs. The cell line retains
      the ability to support neutrophil adhesion and transmigration and can generate
      patent tubes when seeded onto complex basement membrane gels. However, the cell
      line no longer has the ability to generate capillary-like vessels when seeded
      onto collagen gels in the presence of phorbol 12-myristate 13-acetate.
      CONCLUSIONS: C11STH has retained many of the normal characteristics of
      endothelial cells, is able to proliferate at clonal density, and is easily
      transfectable. The line will provide a useful resource for endothelial cell
      biology. Its ability to make capillary-like tubes on basement membrane gels, but
      not on collagen will provide a powerful tool with which to further analyze the
      processes involved in angiogenesis, and will enable us to define the role of
      specific proteins in angiogenesis. Since C11STH shows tube competence on
      Matrigel, but is not tube competent on collagen, our studies suggest that
      capillary-tube formation on Matrigel and collagen occur via qualitatively
      different mechanisms. Thus, this cell line provides the opportunity to examine
      the signalling mechanisms required to generate capillary tube formation. These
      may include the involvement of matrix molecules, the production of proteases and
      inhibitors, gene regulation and kinases or phosphatases.

PMID- 7526036
TI  - Inhibitors of basement membrane collagen synthesis prevent endothelial cell
      alignment in matrigel in vitro and angiogenesis in vivo.
AB  - BACKGROUND: The formation of a basement membrane is the last step in the
      development of a new blood vessel. Matrigel, a laminin-rich reconstituted
      basement membrane matrix induces the differentiation of endothelial cells into
      capillary-like structures. EXPERIMENTAL DESIGN: The effect of inhibitors of
      basement membrane collagen synthesis, tricyclodecan-9-yl xanthate (D609) and 8,9
      dihydroxy-7-methyl-benzo[b] quinolizinium bromide (GPA 1734), was investigated on
      endothelial cell tube formation on Matrigel in vitro and in an angiogenesis assay
      in C57 black mice in vivo. RESULTS: D609 and GPA 1734 caused a dose-dependent
      decrease in tube formation in vitro with complete inhibition at 50 micrograms/ml
      for D609 and 15 micrograms/ml for GPA 1734. The inhibitory effect on capillary
      tube formation by both agents was reversible. Tube formation correlated well with
      collagenous protein biosynthesis. Parallel studies on endothelial cells cultured
      on plastic indicate that cell viability, proliferation, attachment, and
      morphology were not affected by the presence of these collagen inhibitors at
      doses that blocked tube formation and collagen biosynthesis. D609 and GPA 1734
      also inhibited endothelial cell infiltration in response to SIKVAV in an in vivo
      angiogenesis model system. CONCLUSIONS: These results indicate that newly
      synthesised collagen is a prerequisite for expression of the endothelial cell
      phenotype for tube formation and that prevention of collagenous protein
      biosynthesis inhibits tube formation and angiogenesis in vivo.

PMID- 7526038
TI  - Experimental allergic encephalomyelitis. T cell trafficking to the central
      nervous system in a resistant Thy-1 congenic mouse strain.
AB  - BACKGROUND: The understanding of recognition events that underlie the migration
      of antigen-specific T cells to a target organ during immune-mediated damage will
      be integral to the therapy of a number of human conditions of proven or suspected
      autoimmune etiology. In experimental allergic encephalomyelitis (EAE), the
      laboratory model of the human demyelinating disease, multiple sclerosis, previous
      studies have concentrated on susceptible strains and have shown that myelin
      specific T cells play an early, key role in central nervous system (CNS), lesion
      formation. Not known in this model is whether in EAE-resistant strains, similar
      antigen-specific T cells possess the ability to recognize CNS endothelium and
      infiltrate the CNS. EXPERIMENTAL DESIGN: Myelin basic protein (MBP)-responsive T
      cells derived from mice of the C57BL/6 strain (bearing the Thy-1.2 allele) were
      adoptively transferred to the Thy-1.1 congenic strain C57BL/Ka. Some recipients
      were given a subsequent challenge with MBP in adjuvant, a protocol recently shown
      to break resistance in this strain and cause EAE. On the basis of the difference
      in Thy-1 allele, T cell trafficking was followed in this EAE-resistant congenic
      strain following the different sensitization protocols. RESULTS: In C57BL/Ka mice
      receiving adoptively transferred C57BL/6 cells followed by MBP challenge, donor
      MBP-responsive Thy-1.2+ lymphocytes were detected by immunocytochemistry in the
      Thy-1.1 host CNS and also in peripheral lymphoid organs. In mice given MBP
      sensitized cells without additional antigen challenge, although Thy-1.2+ cells
      were found in the spleen and lymph nodes, similar cells could not be found in the
      CNS, and animals displayed neither clinical nor pathologic signs of EAE. Donor T
      lymphocytes appeared in the host CNS with clinical onset, 10 to 14 days after
      challenge. When mice went into remission, Thy-1.2+ lymphocytes could not be found
      in the CNS, but were still present in peripheral lymphoid organs up to 3 months
      after challenge. From the total number of infiltrating cells, T cell receptor
      alpha beta+ cells constituted 27% in perivascular cuffs, 15% in meninges, and 13%
      in the parenchymal infiltrates in the spinal cord. Thy-1.2+ cells contributed up
      to about 40% of total T cell receptor-alpha beta+ lymphocytes. Approximately 60%
      of all infiltrating T cells expressed L3T4 (helper/inducer), whereas 18%
      expressed Lyt-2 (suppressor/cytotoxic). The majority of infiltrating cells were
      memory and activated cells expressing on their surface Pgp-1 and CD 25.
      Immunostaining for cytokines showed that the majority of infiltrating cells
      belonged to the TH1 subset and contained interferon-gamma and tumor necrosis
      factor-alpha, while a minority were positive for interleukin-4. CONCLUSIONS:
      These results suggest that: (a) T lymphocytes from an EAE-resistant strain of
      mouse are capable of homing to the CNS; (b) T lymphocytes from an EAE-resistant
      strain express phenotypic characteristics, activation, memory, and cytokine
      profiles similar to infiltrating cells derived from susceptible strains; and (c)
      the presence of donor T cells in the recipient CNS correlates with clinical and
      histopathologic signs of EAE.

PMID- 7526037
TI  - Ethanol inhibits insulin-like growth factor-1-mediated signalling and
      proliferation of C6 rat glioblastoma cells.
AB  - BACKGROUND: Alcohol consumption during pregnancy often results in disorders of
      fetal development (Fetal Alcohol Syndrome). The brain appears to be particularly
      vulnerable, and alcohol abuse during pregnancy is probably the most common cause
      of acquired mental retardation. We therefore studied the in vitro effects of
      ethanol on insulin-like growth factor-1 (IGF-1)-mediated proliferation of rat C6
      glioblastoma cells. EXPERIMENTAL DESIGN: The proliferation of C6 rat glioblastoma
      cells was measured in serum-free medium supplemented with specific growth factors
      in the presence or absence of ethanol. The effect of ethanol on IGF-1 receptor
      and insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation was determined
      by immunoprecipitation and Western blotting, as was the phosphatidylinositol 3
      kinase content within IRS-1 immunoprecipitates. RESULTS: C6 cells grew slowly in
      serum-free medium and proliferated in response to IGF-1. Ethanol, at
      physiologically tolerated concentrations, markedly inhibited the growth of C6
      cells in response to IGF-1, but had no effect on the proliferative rate in the
      presence of platelet-derived growth factor or 1% fetal bovine serum. Inhibition
      of cell proliferation was evident when ethanol was only present during a 1-hour
      pulse of IGF-1. Cell growth in the presence of IGF-2 was also prevented by
      ethanol. The inhibition of IGF-1-mediated cell proliferation was accompanied by
      abrogation of IGF-1 receptor tyrosine autophosphorylation. Ethanol also
      interfered with the IGF-1-induced tyrosine phosphorylation of IRS-1, and the
      association of phosphatidylinositol-3 kinase with IRS-1. CONCLUSIONS: The data
      indicate that physiologically relevant concentrations of ethanol inhibit the
      responses of glial cells to IGF-1, including IGF-1 receptor autophosphorylation,
      IRS-1 and phosphatidylinositol-3 kinase activation, and cell growth.

PMID- 7526039
TI  - Oval cell lines OC/CDE 6 and OC/CDE 22 give rise to cholangio-cellular and
      undifferentiated carcinomas after transformation.
AB  - BACKGROUND: There is compelling evidence for a parenchymal origin of the
      predominant cell lineage leading from preneoplastic clear and acidophilic
      glycogen storage foci through mixed and basophilic cell populations to
      hepatocellular carcinomas in the rat. However, a controversial question remains
      to be answered: Do the basophilic cell foci invariably originate from parenchymal
      cells or do oval cells also have the potential to give rise to this type of focus
      and progress to hepatocellular neoplasms? Oval cells are nonparenchymal
      epithelial cells with scant cytoplasm and ovoid nuclei that first appear in the
      periportal areas of the liver lobules and thereafter invade the whole parenchyma
      when animals are exposed to high doses of a wide range of chemical carcinogens.
      EXPERIMENTAL DESIGN: Two oval cell lines, OC/CDE 6 and OC/CDE 22, which had been
      established from rats fed a choline-deficient/DL-ethionine-supplemented diet for
      6 or 22 weeks, were transformed either by leaving the cells in confluence for a
      long time period (OC/CDE 6) or by treating the cells with the alkylating agent N
      methyl-N'-nitro-N-nitrosoguanidine. The transformed cells were injected
      subcutaneously in newborn rats and the tumors developing in these animals were
      analyzed histopathologically, ultrastructurally, and immunohistochemically.
      RESULTS: The two transformed oval cell lines gave rise to carcinomas, in which
      cholangiocellular, adenoid and solid tumor formations were observed.
      Subpopulations of these tumors expressed cytokeratins 7, 8, 18, and 19, but were
      albumin- and alpha-fetoprotein-negative. Areas within the carcinomas derived from
      transformed OC/CDE 22 cells representing undifferentiated liver tumor formations
      were also identified. Cells within these areas had lower nucleus/cytoplasm ratios
      than cells in the solid growing tumor formations, stained positive for
      cytokeratins 8 and 18 and were cytokeratin 7- and 19-, albumin- and alpha
      fetoprotein-negative. Ultrastructurally, these cells did not resemble those of
      differentiated hepatocellular carcinomas. CONCLUSIONS: It has been shown that
      oval cells are precursor cells of carcinomas containing cholangiocellular,
      adenoid and solid formations which may be largely undifferentiated. However, the
      transformed OC/CDE 6 or OC/CDE 22 cells do not serve as precursor cells of
      differentiated hepatocellular carcinomas.

PMID- 7526040
TI  - Composition of extracellular matrix and distribution of cell adhesion molecules
      in renal cell tumors.
AB  - BACKGROUND: Cell to cell and cell to matrix interactions play a major role in
      tumor growth and invasion. Therefore, we studied the composition of extracellular
      matrices and the distribution of cell adhesion molecules in 50 renal cell tumors
      of various types and various grades of malignancy as compared with nontumoral
      kidney. EXPERIMENTAL DESIGN: In the present study, we used immunolabeling with
      specific antibodies directed against the alpha 1, alpha 2, and alpha 3 chains of
      collagen type IV; laminin; heparan sulfate proteoglycan; fibronectin; collagen I;
      collagen III; the alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1,
      and beta 3 subunits of integrins; and ICAM-1, VCAM-1, and ELAM-1 molecules.
      RESULTS: In clear cell type carcinomas (24 cases) the basal laminae surrounding
      the tumor islets contained the alpha 1 and alpha 2 chains of collagen type IV and
      heparan sulfate proteoglycan in all cases, and laminin in 96% of the cases. The
      alpha 3 chain of collagen IV was present in only one case, whereas fibronectin,
      collagen I, and collagen III were detected in nearly 50% of the cases. The tumor
      cells expressed alpha 3, alpha 6, and beta 1 integrin subunits in all cases,
      alpha 5 in 25%, alpha v beta 3 in 54%, and alpha 2 in none. ICAM-1 was detected
      in all cases, and VCAM-1 in 58%. The expression of the alpha 6 subunit was weak
      in 2 tumors of high grade, whereas the alpha v subunit was expressed in 7 of 14
      low grade and in 7 of 10 intermediate and high grade tumors. In tubulopapillary
      carcinomas with chromophilic cells (12 cases), the most prominent findings were
      the presence of the alpha 3 chain of collagen IV in tumor basal laminae in 66%
      and the expression of the alpha 2 integrin subunit by the tumor cells in 58% of
      the cases, both features characterizing distal renal tubules. In chromophobic
      carcinomas (4 cases), the tumor basement membranes were tenuous and contained no
      fibronectin or interstitial collagens. The tumor cells expressed the alpha 6,
      alpha 2, alpha 3, beta 1, and alpha nu beta 3 integrin subunits but neither ICAM
      1 nor VCAM-1 molecules. In oncocytomas (10 cases), the tumor basement membranes
      contained the alpha 1, alpha 2, and alpha 3 chains of collagen IV, laminin, and
      heparan sulfate proteoglycan. Fibronectin was not detected, whereas interstitial
      collagens were present in half of the cases. In all tumors, cells expressed the
      alpha 6 and beta 1 integrin subunits, whereas alpha 2, alpha 3, and alpha nu beta
      3 were present in 30%, 60%, and 90% of the cases, respectively. ICAM-1 and VCAM-1
      were not detected. The vascular endothelial cells of the stroma expressed the
      alpha 1, alpha 5, alpha 6, and beta 1 integrin subunits in all 50 of the studied
      tumors. In addition, ICAM-1 was detected in 84%, VCAM-1 in 50%, and ELAM-1 in 34%
      irrespective of tumor cell type, growth, or nuclear grade. CONCLUSIONS: These
      results suggest that each type of renal cell tumor produces particular
      extracellular matrix components and expresses a characteristic repertoire of cell
      adhesion molecules, which could provide better understanding of the origin of
      these tumors. The expression of the alpha nu beta 3 integrin subunit was
      demonstrated in all types of renal cell tumors and was not found to be related to
      high grade tumors. Stromal vascular endothelial cells expressed activation
      molecules VCAM-1 and ELAM-1 in a significant number of cases in both benign and
      malignant tumors.

PMID- 7526042
TI  - Facilitating prelinguistic communication skills in young children with
      developmental delay. II: Systematic replication and extension.
AB  - Four children with mental retardation were studied in the context of a multiple
      baseline across subjects design. Staff members used a modified version of the
      milieu teaching method to facilitate intentional requesting. The results
      replicated the finding that a modified version of milieu teaching was effective
      in facilitating the use of intentional requesting by children with developmental
      delays in an intervention context (Warren, Yoder, Gazdag, Kim, & Jones, 1993).
      This study also extended the Warren et al. (1993) work by (a) documenting that
      increased intentional requesting generalized to sessions with the children's
      mothers, (b) demonstrating that mothers who were naive to the purposes of the
      study were more likely to linguistically map their children's prelinguistic
      communication after the intervention than before the treatment, and (c) that
      mothers and teachers who were naive to the purposes of the study linguistically
      mapped the children's intentional communication more than the children's
      preintentional communication. We discuss implications of these results for early
      intervention, the transactional theory of development, and the importance of the
      distinction between intentional versus preintentional communication.

PMID- 7526041
TI  - Immunochemical localization of inducible nitric oxide synthase in endotoxin
      treated rats.
AB  - BACKGROUND: Administration of endotoxin to rodents produces widespread tissue
      induction of nitric oxide synthase (NOS). To understand the mechanisms of the
      resulting endotoxin shock, it is important to know the cellular distribution of
      the inducible NOS (iNOS). EXPERIMENTAL DESIGN: We have investigated the
      localization and time course of expression of iNOS in rats at time 0 (control)
      and 3, 6, 9, and 24 hours after administration of endotoxin and also in endotoxin
      and cytokine-stimulated RAW 264 murine macrophage and A7r5 aortic smooth muscle
      cells. We have used a rabbit antiserum to a synthetic peptide selected from the
      deduced sequence of the cloned macrophage enzyme (residues 47-71) and
      immunochemical techniques. RESULTS: The antiserum reacted with an approximately
      130-kilodalton protein (the molecular weight of iNOS) in Western blots of total
      cytoplasmic proteins from livers of endotoxin-treated rats, RAW 264 murine
      macrophages stimulated with endotoxin and combinations of cytokines, and purified
      liver iNOS, but not in control, untreated tissues. Strong cytoplasmic
      immunostaining was seen in RAW 264 murine macrophages and A7r5 rat aortic smooth
      muscle cells after stimulation, but not in nonstimulated cells. Three hours after
      endotoxin treatment in rats, iNOS immunoreactivity was detectable in many tissues
      and was at its strongest at 6 and 9 hours after stimulation. Staining was
      detected predominantly in macrophages distributed abundantly in heart, lung,
      liver, and kidney. It was also present in Kupffer cells and hepatocytes, biliary
      epithelium, mesangial cells, airway epithelium, and nerves supplying mesenteric
      blood vessels but was not detected in any vasculature. By 24 hours there was a
      reduction in the number of cells stained compared with that seen at 6 and 9
      hours. In addition, at 24 hours after endotoxin treatment, granulomatous lesions
      showing iNOS staining were evident, particularly in the liver. CONCLUSIONS:
      Antiserum raised to macrophage NOS recognizes an inducible enzyme in a wide
      variety of cells. Macrophages are the major site of iNOS expression in endotoxin
      treated rats and show greatest staining between 6 and 9 hours after treatment.
      Although staining was not seen in vascular cells in vivo, levels of the enzyme
      that are below the immunocytochemistry detection limit cannot be excluded.

PMID- 7526044
TI  - Elevation of circulating monitor peptide/pancreatic secretory trypsin inhibitor-I
      (PSTI-61) after turpentine-induced inflammation in rats: hepatocytes produce it
      as an acute phase reactant.
AB  - Monitor peptide (MP) is a trypsin-sensitive cholecystokinin (CCK)-releasing
      peptide purified from rat pancreatic juice on the basis of its stimulatory
      activity toward pancreatic enzyme secretion and has been reported to exhibit cell
      growth-stimulating activity. Pancreatic secretory trypsin inhibitor (PSTI)
      prevents premature activation of trypsinogen in the pancreatic duct. There are
      two PSTIs (PSTI-61 and -56) purified from rat pancreatic juice on the basis of
      trypsin inhibitory activity as reported previously. Fushiki et al. (1989, FASEB
      J. 3, 121) showed that MP is structurally the same peptide as PSTI-61. We
      measured the serial changes of circulating MP/PSTI-61 in rat and those in the
      level of PSTI-61 mRNA in the rat liver to investigate another novel role of this
      peptide in the turpentine-induced acute inflammation model. The elevation of
      serum MP/PSTI-61 as well as the alpha 2-globulin fraction, which is known to
      include several acute phase reactants such as alpha 2-macroglobulin and
      haptoglobin, was observed after induction of the turpentine inflammation. The
      serum alpha 2-globulin fraction had increased approximately 3-fold over the
      initial level at 48 hr after the injection. In contrast, serum MP/PSTI-61 had
      increased approximately 17-fold over the initial level at 48 hr after the
      injection. The elevation of circulating MP/PSTI-61 was significantly related with
      that of the alpha 2-globulin fraction (r = 0.91, P < 0.01). Immunoreactive
      MP/PSTI-61 was detected in the liver after induction of the inflammation (152.5
      +/- 16.5 ng/g wet weight), but in the normal rat liver there was no
      immunoreactive MP/PSTI-61.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526043
TI  - Increased heart rate and blood pressure response, and occurrence of arrhythmias
      in elderly swimmers.
AB  - Changes in the heart rate (HR) and blood pressure, and the occurrence of
      arrhythmias after swimming were examined in 52 members of swimming classes aged
      40 to 76 years. After swimming 25 m twice at a usual intensity, HR increased
      markedly in the subjects to 87 +/- 11% of predicted maximal HR, while the rate of
      perceived exertion was modest. The systolic blood pressure (SBP) also increased
      significantly, and SBP of 200 mmHg or higher was exclusively observed in subjects
      60 years or older. After entering the pool, immersing the face and swimming, 28
      subjects (54%) developed various arrhythmias. Premature ventricular contraction
      (PVC) was provoked or aggravated by swimming in 19 subjects. The incidence of PVC
      provocation or aggravation increased as SBP at rest or age increased. Swimming
      causes marked rise in HR and SBP in elderly subjects, and frequently provokes or
      aggravates PVC in older subjects and/or in subjects with higher SBP at rest.

PMID- 7526045
TI  - Transforming growth factor-beta 1 lowers the CD14 content of monocytes.
AB  - Marked elevation of transforming growth factor-beta 1 (TGF-beta 1) has been
      demonstrated clinically following injury and in sepsis. While alterations in the
      monocyte binding site (CD14) for the lipopolysaccharide (LPS)-lipopolysaccharide
      binding protein (LBP) complex have been noted with exposure to LPS, immune
      complexes, gamma-interferon, and IL-4, it is not known whether TGF-beta 1 can
      alter CD14 expression. To study the effect of TGF-beta 1 on monocyte CD14
      expression, human leukocytes were isolated from healthy donors with discontinuous
      gradient centrifugation and incubated at 37 degrees C for 2 and 24 hr with
      increasing doses of purified human platelet TGF-beta 1. Monocytes were
      immunofluorescently stained with monoclonal antibodies recognizing CD14 and CD16.
      The cells were analyzed by flow cytometry. At 2 hr, 50 ng/ml TGF-beta 1
      significantly lowered CD14 expression (51%, P = 0.043). At 24 hr, there was no
      significant difference between cells stimulated by TGF-beta 1 and control cells.
      To confirm that TGF-beta 1 was active at 24 hr, we examined levels of CD16. CD16
      expression was increased by 10 ng/ml of TGF-beta 1. These observations suggest
      that high physiologic concentrations of TGF-beta 1 cause early monocyte
      suppression of CD14. Thus, CD14 may be marker for the transition of monocytes to
      macrophages and TGF-beta 1 may be responsible for the down-regulation of CD14
      expression observed in monocytes obtained from septic patients.

PMID- 7526047
TI  - Molecular and functional studies of inhibitory G protein in RINm5F cells.
AB  - Inhibitory G proteins (Gi) play an important role in cell proliferation. In order
      to characterize Gi proteins in RINm5F (RIN) cells, we first established RIN cells
      in cell culture. Immunoblot analysis was performed on extracted G proteins using
      Western blot techniques and a Gi-specific antibody. We identified three prominent
      bands consistent with three distinct inhibitory alpha subunits of membrane-bound
      G protein (Gi) in RIN cells. In contrast, we identified only one prominent
      distinct inhibitory alpha subunit of G protein in an equal quantity of membrane
      protein in our control (normal rat pancreas). In several cell types, Gi is known
      to mediate the inhibitory action of somatostatin on intracellular cyclic AMP
      (cAMP) accumulation. Therefore, we studied the action of the long-acting analogue
      of somatostatin, octreotide (SMS), on basal and 3-isobutyl-1-methylxanthine
      stimulated cAMP accumulation in RIN cells. SMS did not inhibit cAMP accumulation
      or tritiated thymidine incorporation into DNA (TTID) in RIN cells. However, when
      treatment with SMS is supplemented with the nonhydrolyzable analogue of guanine
      nucleotide, Gpp(NH)p (Gpp), which is known to dissociate G proteins into its
      constitutive subunits, then SMS+Gpp induced an inhibitory action and
      significantly reduced cAMP accumulation and TTID. These data are consistent with
      the concept of qualitatively and functionally altered inhibitory G protein
      expression in the insulin-producing, islet cell (RINm5F) rat insulinoma tumor
      cell line. Further study of human tumors will lead to new insights into the
      clinical implications of G protein-mediated signal transduction in insulinoma.

PMID- 7526046
TI  - FGF-1 affixation stimulates ePTFE endothelialization without intimal hyperplasia.
AB  - The affixation of FGF-1 to porous vascular grafts has been reported to stimulate
      capillary ingrowth and surface endothelialization. The current study further
      characterizes responses to fibroblast growth factor (FGF)-1 affixation to 30-cm
      long grafts followed 140 days. ePTFE grafts (30 cm x 8 mm i.d.), 60 microns
      internodal distance, were impregnated with fibrin glue (FG) suspensions
      containing FGF-1 and heparin. Two negative control groups were treated either
      with FG with heparin alone or left untreated. Grafts were explanted from the
      canine thoracoabdominal aortic position after 10, 30, or 140 days (n =
      3/time/group) 10 hr after im injection of tritiated thymidine (0.5 muCi/kg).
      Specimens were studied by light and electron microscopy, immunohistochemistry,
      morphometric analyses, and cross-sectional autoradiography. RNA preparations from
      inner capsule tissues were used for reverse transcription-polymerase chain
      reaction (RT-PCR) analyses of FGF-1, FGF-2, transforming growth factor-beta 1,
      (TGF-beta 1) and FGF receptor mRNA species. Inner capsule collagen was
      quantitated by hydroxyproline colorimetry. Histologic analyses of perianastomotic
      regions were performed for comparison purposes. All explants were patent and
      without intimal hyperplasia. Progressive capillarization of the internodal spaces
      occurred over time and was significantly more extensive in the FGF-1-treated
      group. Endothelialization of the luminal surface increased with time, at 140 days
      covering 86.7 +/- 11.6% of the FGF-1 explants vs 46.1 +/- 7.5% and 48.1 +/- 13.3%
      in the other groups, P < 0.007 and P < 0.04, respectively. Inner capsule
      thickness at 140 days differed significantly (P < 0.05) between the FGF-1 group
      (138.8 microns) vs either control group (93 and 67 microns, respectively), which
      did not significantly differ from each other. Cross-sectional autoradiography
      demonstrated an FGF-1-induced mitotic index increase at 30 days, 9.6 +/- 4.4%
      compared to 2.5 +/- 1.0 and 0 +/- 0%, respectively, with both myofibroblasts and
      endothelial cells incorporating the [3H]thymidine label. The mitotic index
      returned to quiescent levels at 140 days (< 1% in all groups). Collagen content
      increased with time in all groups, significantly greater in both FG groups vs
      untreated controls at 30 and 140 days. RT-PCR analyses revealed FGF-1, FGF-2,
      FGFR-1 (flg), and TGF-beta 1 mRNA in all samples without evidence of modulation
      by FGF-1 affixation. These data demonstrate FGF-1-induced graft capillarization
      and surface endothelialization without functionally significant intimal
      hyperplasia in this model.

PMID- 7526048
TI  - Use- and concentration-dependent effects of flecainide in guinea pig right
      ventricular muscle.
AB  - In clinical studies, flecainide, a class IC antiarrhythmic drug, exhibited
      antiarrhythmic properties against supraventricular arrhythmias but also showed
      proarrhythmic effects in ventricular arrhythmias. We studied the effects of
      flecainide on action potential (AP) maximum rate of increase (Vmax) in guinea-pig
      right ventricular muscle. The effects of flecainide were studied at 3
      concentrations (10(-5), 5 x 10(-6), 10(-6) M) and five frequencies (0.5, 1, 1.5,
      2, and 3 Hz). At these three concentrations, flecainide caused little and not
      significant tonic block. In contrast, flecainide caused a frequency-and dose
      dependent reduction in Vmax (at 3 Hz, the time constant of Vmax decrease was 3.6
      +/- 0.2 s for 10(-5) M, 3.8 +/- 0.2 s for 5 x 10(-6) M, and 7.1 +/- 1.3 s for 10(
      6) M). At 3 Hz, the time constants measured as number of APs were 11 +/- 2 for
      flecainide 10(-5) M, 12 +/- 2 for 5 x 10(-6) M, and 22 +/- 2 for 10(-6) M,
      respectively. At 10(-6) M, spontaneous arrhythmias occurred at all frequencies
      studied. Assuming that changes in Vmax reflect changes in Na+ fast current
      amplitude, our results suggest that flecainide is an open Na channel blocker
      showing frequency- and dose-dependent effects in the range of 0.5-3 Hz.

PMID- 7526049
TI  - Centrally mediated reduction in cardiac output elicits the enhanced hypotensive
      effect of clonidine in conscious aortic barodenervated rats.
AB  - In a previous study, we showed that centrally mediated hypotensive responses are
      enhanced in aortic barodenervated (ABD) rats as compared with sham-operated (SO)
      rats. In the present study, we tested the hypothesis that the high basal total
      peripheral resistance (TPR) of ABD rats accounts for enhanced hypotensive
      responses to clonidine in this rat model. Aortic barodenervation resulted in
      acute increases in blood pressure (BP) and heart rate (HR) in anesthetized rats,
      associated with significant increases in plasma norepinephrine (NE) levels and
      TPR; cardiac index (CI) and stroke volume (SV) were not affected. After recovery
      from anesthesia, conscious ABD rats had significantly increased BP at 3 h after
      barodenervation; BP returned to SO levels by 48 h even though plasma NE levels
      and TPR remained significantly increased. On the other hand, CI and SV showed
      significant reductions, beginning at 3 h, and remained low throughout the
      postdenervation period (48 h); the reduction in CI offset the increase in TRP and
      may therefore account for the restoration of BP of ABD rats to normal levels.
      Beginning at similar baseline BP values, cumulative intracisternal (i.c.) doses
      of clonidine (0.02-2.5 micrograms) elicited greater decreases in BP and plasma NE
      levels in conscious ABD as compared with SO rats. These responses were centrally
      mediated because systemic administration of 0.12 micrograms clonidine, a dose
      that elicited near maximal hypotensive response after i.c. administration,
      affected neither BP nor plasma NE levels. Contrary to the hypothesis, the
      hypotensive effect of clonidine in ABD rats resulted exclusively from a reduction
      in CO (owing to reductions in both HR and SV) because TPR was not affected. These
      findings suggest that (a) in ABD rats, a reduction in CO offsets a sustained
      sympathetically mediated elevation in TPR and restores BP to normal levels; and
      (b) an enhanced hypotensive response to clonidine in ABD as compared with SO rats
      cannot be accounted for by a higher basal TRP but rather by elicitation of
      greater reductions in CO through a centrally mediated sympathoinhibitory action.

PMID- 7526050
TI  - Safety of concomitant potassium-sparing diuretics in angiotensin-converting
      enzyme inhibitor therapy in severe congestive heart failure. Xamoterol in Severe
      Heart Failure Study Group.
AB  - The safety of concomitant use of angiotensin-converting enzyme (ACE) inhibitors
      and potassium-sparing diuretics (PSD) in severe heart failure remains a
      controversial issue. The database of the recently reported double-blind
      international trial, "Xamoterol in Severe Heart Failure," was investigated to
      elucidate this question. Of 516 patients with New York Heart Association (NYHA)
      class III-IV, despite diuretics and ACE inhibitor therapy, 352 were randomized to
      xamoterol, a beta 1 partial agonist, and 164 were randomized to placebo. During
      the 13-week study, 28% of all patients (xamoterol, 104; placebo, 42) received
      potassium-sparing diuretics. All groups were comparable in hemodynamics and dose
      of other diuretics. At study end, patients with or without PSD showed no
      significant differences in serum K+ or creatinine, independent of xamoterol or
      placebo therapy. Mortality rate was consistently lower: 4.6% in patients with PSD
      and 8.5% in patients without PSD, although statistical significance was not
      reached. As compared with baseline, K+ values of 6 patients with and 17 patients
      without PSD had increased by > 5.0 mM at study end (p = NS); 1 patient with and
      11 patients without PSD had a creatinine level > 180 microM (p = NS). For 3
      patients receiving PSD, and 2 patients not receiving PSD because of renal
      impairment, study was discontinued because of hyperpotassemia. No significant
      differences were noted in long and short action or different dosages of ACE
      inhibitors. PSD may be administered concomitantly with ACE inhibitors, but serum
      K+ should be monitored as with other diuretics.

PMID- 7526051
TI  - Comparative effects of increased extracellular potassium and pacing frequency on
      the class III activities of methanesulfonanilide IKr blockers dofetilide, D
      sotalol, E-4031, and MK-499.
AB  - The methanesulfonanilide-containing Class III agents dofetilide, D-sotalol, E
      4031, and MK-499 have been characterized as selective blockers of a rapidly
      activating component of the cardiac delayed rectifier (IK) K+ current, IKr. In
      the present studies, the effects of dofetilide (3-30 nM), D-sotalol (10-100
      microM), E-4031 (30-300 nM), and MK-499 (30-300 nM) on myocardial effective
      refractory period (ERP) were assessed in ferret right ventricular papillary
      muscles in conditions of altered extracellular K+ concentration ([K+]e[normal (4
      mM) versus increased (10 mM)] concentrations, and of altered pacing frequency (1
      3 Hz). With 4 mM [K+]e, all four agents elicited significant, concentration
      dependent ERP increases in the frequency range of 1-3 Hz, and all four agents
      displayed reverse frequency-dependent activity. Reverse frequency-dependent
      profiles also were demonstrable in 10 mM [K+]e at the higher test agent
      concentrations; dofetilide (10 and 30 nM), D-sotalol (100 microM), E-4031 (100
      and 300 nM) and MK-499 (100 and 300 nM). All four agents displayed diminished ERP
      increases in increased versus normal [K+]e. Among individual test agents,
      however, there were differences in magnitudes of diminution of ERP increases
      observed in increased [K+]e: The activities of D-sotalol and MK-499 were better
      maintained in increased [K+]e than were those of dofetilide and E-4031. As a
      result of this differential sensitivity increased [K+]e, significant ERP
      increases were not demonstrable for dofetilide and E-4031 in simultaneous
      conditions of increased [K+]e and rapid pacing, whereas significant activities
      were maintained with D-sotalol and MK-499 in increased [K+]e throughout the 1-3
      Hz range of pacing frequencies. However, the inherent tendency of myocardial
      refractoriness to increase in increased [K+]e, particularly at faster pacing
      frequencies, played a dominant role in determining the relationship between
      increased versus normal [K+]e posttreatment ERP in all Class III treatment
      groups. This frequency-dependent increment in refractoriness in increased [K+]e
      reflected in baseline ERP determined in 10 versus 4 mM [K+]e, respectively, at
      frequencies of 1 Hz (163 +/- 3 vs. 157 +/- 2 ms, p = 0.06), 2 Hz (146 +/- 3 vs.
      134 +/- 2 ms, p < 0.01), and 3 Hz (134 +/- 2 vs. 112 +/- 2 ms, p < 0.01) tended
      to offset as well as minimize differences among the IKr blockers in diminution of
      activity observed in increased [K+]e.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7526052
TI  - Hemodynamic and coronary vasodilative properties of a selective and full beta 1
      adrenoceptor agonist, T-0509, in comparison with isoproterenol in anesthesized
      dogs.
AB  - Recently, the beta 1-adrenoceptor was shown to mediate direct coronary
      vasodilation independent of metabolic demand in canine arrested heart
      preparation. To investigate the beta 1-adrenoceptor-mediated direct vasodilation
      in a beating heart preparation, we compared coronary blood flow (CBF) and
      coronary sinus oxygen tension (PO2) in anesthetized open-chest dogs using a beta
      1-selective agonist, T-0509. T-0509 (0.005-0.05 microgram/kg intravenously, i.v.)
      increased the maximal rate of increase in left ventricular pressure (LVdp/dtmax)
      and heart rate (HR) to an extent similar to that induced by isoproterenol (ISO)
      without decreasing diastolic blood pressure (DBP). A beta 1-adrenoceptor
      antagonist, (-)-bisoprolol (10 micrograms/kg), but not a beta 2-adrenoceptor
      antagonist, ICI 118,551 (30 micrograms/kg), inhibited the T-0509-induced increase
      in LVdp/dtmax and HR. Thus, T-0509 showed selective beta 1 stimulation at the
      doses used. T-0509 also caused beta 1-selective relaxation in isolated coronary
      arteries. ISO increased both CBF and PO2. The early phase of the increase in CBF
      and the concurrent increases in PO2 were inhibited by ICI 118,551, whereas the
      late phase of the increase in CBF was inhibited by (-)-bisoprolol. T-0509
      increased CBF, and this increase was inhibited by (-)-bisoprolol. A slight but
      significant increase in PO2 induced by T-0509 was not altered by these doses of
      the antagonists. Our results indicate that the T-0509-induced increase in CBF is
      due mainly to an indirect effect on myocardial beta 1-adrenoceptors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7526053
TI  - Functional and morphologic characterization of thoracic aorta in heritable
      hyperlipidemic Yoshida rats of different ages.
AB  - We investigated serum and aortic tissue lipid content, in vitro aortic response
      to drugs, and morphology of thoracic aorta in Pittsburgh Yoshida rats (YOS), a
      new animal model of endogenous hyperlipidemia. Experiments were performed on 2-,
      6-, and 18-month-old rats. Normolipidemic Brown Norway rats (BN) were used as
      controls. Both serum cholesterol and triglycerides increased significantly with
      age in YOS rats, but remained constantly low in the control group. In YOS rats,
      absolute serum concentration of high density lipoprotein (HDL)-cholesterol
      increased significantly with age, although HDL-cholesterol/total-cholesterol
      ratio decreased. In contrast, no difference in cholesterol content in aortic
      tissue was detected between the two animal strains or among different age groups.
      The contractile force generation of thoracic aorta to norepinephrine (NE) and
      serotonin increased with age in both strains of animals. The endothelium
      dependent relaxation induced by acetylcholine (ACh) was significantly reduced in
      6- and 18-month-old YOS as compared with 2-month-old YOS but not in BN. ATP
      induced relaxation was significantly impaired in YOS thoracic aorta. In contrast,
      the relaxation induced by NaNO2 acting in smooth muscle did not vary with age in
      either YOS or BN. Only alterations in endothelial cells, not typical atheromatous
      injuries in thoracic aorta wall were detected in YOS even at age 18 months. Our
      data indicate that despite high serum lipid levels, YOS do not develop typical
      atheromatous lesions or functional and morphologic damage of smooth muscle cells
      in thoracic aorta, whereas YOS show decreased endothelium-dependent relaxation
      and morphologic alteration of endothelial cells.

PMID- 7526054
TI  - Recombinant human hemoglobin inhibits both constitutive and cytokine-induced
      nitric oxide-mediated relaxation of rabbit isolated aortic rings.
AB  - A genetically engineered recombinant human hemoglobin (rHb1.1) was recently
      developed for use as a blood substitute (Nature 1992;356:258-60). Like other
      mammalian hemoglobin (Hb) molecules, it might bind and antagonize the actions of
      nitric oxide (NO). We used an isolated rabbit aortic ring preparation to examine
      the ability of rHb1.1 to inhibit acetylcholine (ACh)- and interleukin-1 beta (IL
      1 beta)-induced reductions of vasoconstrictor responses to the alpha-adrenoceptor
      agonist phenylephrine (PE). rHb1.1 (0.04-4.4 microM) rapidly and reversibly
      inhibited, in a concentration-dependent manner, both ACh- and IL-1 beta-induced
      decreases in PE contractile responses. These inhibitory effects of rHb1.1 were
      non-competitive and were equipotent to those of purified, cell-free human Hb
      (p.hHb). These two forms of soluble Hb were at least 10 times more potent than Hb
      in erythrocytes (red blood cells: RBC-Hb). Both NG-nitro-L-arginine (10 microM) a
      NO synthase inhibitor, and LY-83583 (10 microM), a guanylyl cyclase inhibitor,
      mimicked the effects of rHb1.1. The inhibitory effects of rHb1.1 were not shared
      by either human serum albumin (HSA 44 microM), which combines with but does not
      deactivate NO, or cytochrome C (44 microM), a heme-containing protein that does
      not bind NO; neither were they reversed by L-arginine (L-ARG) (1 mM), the
      presumed NO precursor. These and other results suggest that the chemical
      antagonism of NO is likely to be the mechanism by which rHb1.1 and other Hbs
      inhibit ACh- and IL-1 beta-induced decreases in the response to PE in rabbit
      aortic rings.

PMID- 7526056
TI  - Comparison of the efficacy of three dose levels of moexipril versus placebo as
      add-on therapy to hydrochlorothiazide in patients with moderate hypertension.
AB  - This parallel, double-blind trial was designed to evaluate the efficacy of three
      dose levels of moexipril versus placebo as add-on therapy to hydrochlorothiazide
      (HCTZ) in patients with uncomplicated moderate to severe hypertension. Two
      hundred patients (aged 25-74 years) with sitting diastolic blood pressure (DBP)
      between 95 and 114 mm Hg after 4 week treatment with HCTZ 25 mg once daily were
      randomized to placebo, or moexipril 3.75, 7.5 mg, or 15 mg. BP was measured at 22
      26 h postdose at biweekly visits and at 1, 2, 3, and 4 h postdose after the first
      dose of double-blind medication. At endpoint, adjusted mean reductions from
      baseline sitting DBP were 8.4, 8.8, and 8.9 mm Hg in the moexipril 3.75-, 7.5-,
      and 15-mg groups, respectively, as compared with a reduction of 4.6 mm Hg in the
      placebo group (p = 0.003). The differences in systolic BP (SBP) reductions were
      statistically significant in favor of each of the moexipril groups over the
      placebo group at all trough time-points. Adjusted mean changes in sitting SBP
      were 10.9, 12.0, and 11.7 mm Hg, respectively, as compared with a reduction of
      0.6 mm Hg in the placebo group (p < 0.001). Our results indicate that moexipril
      and HCTZ constitute a clinically valuable combination in treatment of patients
      with moderate to severe hypertension.

PMID- 7526055
TI  - Role of the cytochrome P450 enzyme system as a humoral modulator of vasomotor
      responses in rat renal vasculature.
AB  - This study was conducted to examine regulation of vasomotor tone by cytochrome
      (cyt) P450 enzymes. Isolated perfused rat kidney was used to examine the
      vasoconstrictor responses to KCl, phenylephrine (PE), and 5-hydroxytryptamine (5
      HT) in the presence of inhibitors of cytP450 enzymes. Vasoconstriction elicited
      by KCl 2.5-7.5 mg, PE 0.1-1.0 microgram, and 5-HT 10-50 ng was attenuated dose
      dependently after acute inhibition of cytP450 enzymes with alpha NF 2.5-10 microM
      and clotrimazole 0.1-3.0 microM. Similarly, depletion of cytP450 enzymes with
      CoCl2 significantly inhibited the vasoconstrictor responses to KCl and PE. These
      inhibitory effects were greater against KCl and PE, suggesting that release of
      endogenous arachidonic acid (AA) and its conversion to cytP450 vasoconstrictor
      products by these agonists may contribute to their vasoconstrictor activities.
      The renal microsomal oxidation of ethylene glycol to formaldehyde (cytP450IIE1
      activity) was markedly inhibited by these inhibitors. In addition, conversion of
      radiolabeled AA ([14C]AA) by the indomethacin-treated kidney was reduced by
      CoCl2. Without indomethacin added, exogenous AA amplified vasoconstrictor
      responses whereas, with indomethacin added, AA attenuated vasoconstrictor
      responses. Clotrimazole inhibited both responses, suggesting involvement of a
      combination of cyclooxygenase-dependent and cyclooxygenase-independent cytP450
      product(s). In Ca(2+)-free Krebs buffer containing 0.1 mM EGTA, vasoconstriction
      elicited by CaCl2 (2.5, 5, and 10 mg) was inhibited only moderately by
      clotrimazole 1 and 3 microM and alpha-naphthoflavone (alpha NF 2.5 and 5 microM),
      suggesting that the inhibitory effect of these agents may also proceed by an
      independent but less important mechanism involving interference with Ca2+ flux
      across membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526057
TI  - Prevention of tricyclic antidepressant-induced ventricular tachyarrhythmia by a
      specific bradycardic agent in a canine model.
AB  - Sinus tachycardia facilitates ventricular conduction delay and sustained
      ventricular tachyarrhythmias during tricyclic antidepressant overdose. We
      hypothesized that impeding sinus tachycardia with the specific bradycardia agent,
      UL-FS 49, would reduce the incidence of ventricular tachyarrhythmia caused by
      tricyclic antidepressant overdose and tested this hypothesis in a canine model of
      ventricular tachycardia (VT) induced by graded amitriptyline infusion (0.5-1.0
      mg/kg/min) during continuous hemodynamic monitoring. Three groups were studied. A
      control group (group A, n = 8) received amitriptyline infusion alone. A
      pretreated group (group B, n = 8) received UL-FS 49 (1 mg/kg intravenously, i.v.)
      45 minutes before amitriptyline infusion. A treatment group (group C, n = 5)
      received UL-FS 49 (1 mg/kg) during amitriptyline infusion after onset of
      ventricular tachyarrhythmia. Seven (88%) in group A had ventricular
      tachyarrhythmia at 35 +/- 6 min of amitriptyline infusion. Ventricular
      tachyarrhythmia did not occur in any (0%) animal in group B. Peak sinus heart
      rate (HR) was significantly higher in group A (160.0 +/- 9.8 beats/min) than in
      group B (92.8 +/- 5.3 beats/min; p < 0.0001). Unimpeded sinus tachycardia in
      group A was associated with a significantly longer QRS duration (158.8 +/- 7.4
      ms) as compared with group B (101.0 +/- 2.3 ms; p < 0.0001). UL-FS 49 did not
      influence systolic blood pressure (SBP) at baseline or during amitriptyline
      infusion. In group C, 3 of 5 dogs with nonsustained VT (NSVT) had effective sinus
      rate slowing and suppression of all NSVT after UL-FS 49. UL-FS 49 did not
      terminate SVT in 2 of 5 group C dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526058
TI  - Alpha 1-adrenoceptor stimulation increases 86Rb+ influx in perfused rat heart.
AB  - Stimulation of myocardial alpha 1-adrenoceptors has been shown to mediate various
      changes in potassium fluxes across the sarcolemma. We studied the early effect of
      alpha 1-adrenoceptor stimulation [5 x 10(-5) M phenylephrine (PE) with 10(-6) M
      timolol] on potassium influx by measuring uptake of 86Rb+ into isolated rat heart
      perfused in a nonrecirculating system. The hearts were exposed to alpha 1
      adrenoceptor stimulation with or without the Na+/K(+)-ATPase inhibitor ouabain
      (10(-5) M) during the influx period of 86Rb+ and during the subsequent washout
      period. 86Rb+ content in the perfusate fractions during the washout period and in
      heart at the end of experiments were measured. From these data, 86Rb+ content in
      heart after 2.5, 5.5, and 9.5 min was calculated. alpha 1-adrenoceptor
      stimulation increased 86Rb+ uptake by 20-40% during the observation period. The
      influence of ouabain did not indicate clear-cut involvement of Na+/K(+)-ATPase in
      this effect. The alpha 1-adrenoceptor antagonist prazosin (10(-6) M) prevented
      the effects of PE. Therefore, increase in potassium influx is mediated by alpha 1
      adrenoceptors.

PMID- 7526060
TI  - Effects of a newly synthesized dihydropyridine, NZ-105, on intracellular Ca
      transients and tension in ferret ventricular muscles.
AB  - We investigated the effects of a newly synthesized dihydropyridine (DHP)
      derivative (NZ-105) on intracellular Ca transients and contraction in ferret
      ventricular muscles, using the aequorin method. Low concentrations of NZ-105 (10(
      9)-10(-7) M) showed no significant effects on the light signal of aequorin and
      tension in twitch. High concentrations of NZ-105 (10(-6)-10(-5) M) inhibited the
      peaks of the light signal and tension without altering their time courses. The
      relation between the peaks of the light signal and tension in twitch, measured in
      solutions with varying Ca2+ concentrations, was shifted to the left by NZ-105.
      The relation between [Ca2+]i and tension measured in tetanic contraction was also
      shifted to the left by NZ-105. These results suggest that the inhibitory effect
      of NZ-105 on contraction in mammalian cardiac muscle is curtailed by an increase
      in Ca sensitivity of the contractile elements.

PMID- 7526059
TI  - Rapid development of nitrate tolerance in healthy volunteers: assessment using
      spectral analysis of short-term blood pressure and heart rate variability.
AB  - Nitrate tolerance is characterized by a loss of nitroglycerin (NTG) vasodilating
      and hypotensive effects during continuous administration, but is difficult to
      detect clinically. We hypothesized that the decrease in arterial blood pressure
      (BP) and the reflex sympathetic activation and tachycardia due to baroreflex
      deactivation associated with rapid intravenous (i.v.) infusion of NTG would be
      decreased during continuous NTG patch therapy as a result of tolerance to
      transdermal NTG. Sympathetic activation was measured as the change in amplitude
      of low-frequency (66-129 mHz) oscillations in BP and heart rate (HR) recorded by
      a noninvasive method. Eleven healthy male volunteers received rapid i.v. infusion
      of 0.45 mg NTG in 1 min on 3 consecutive days: before NTG patch, after 22.5 h of
      patch therapy, and 22.5 h after patch removal. The maximum decrease in systolic
      BP (SBP) and maximum reflex tachycardia as well as the sympathetic activation
      produced by i.v. NTG were compared during each of the three study periods. The
      maximum decrease in SBP was 38 +/- 8 mm Hg before NTG patch and 27 +/- 15 mm Hg
      during NTG patch (p < 0.05), with return to baseline values (37 +/- 13 mm Hg)
      after patch removal. There was no significant change in amplitude of reflex
      tachycardia among study periods. However, low-frequency oscillations in SBP
      increased by 40 +/- 31% in the absence of NTG patch and by only 9 +/- 35% after
      22.5 h of patch therapy (p < 0.05). Patch removal resulted in a significant
      rebound increase in these oscillations (70 +/- 51%; p < 0.05 vs.
      baseline).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526061
TI  - Possible mechanisms for the inhibitory effect of Ruscus extract on increased
      microvascular permeability induced by histamine in hamster cheek pouch.
AB  - Extract of Ruscus aculeatus is used in treatment of venous insufficiency. In the
      present study, we used the hamster cheek pouch preparation and investigated in
      vivo the effects of an alpha 1 and alpha 2 adrenoceptor antagonists, a calcium
      blocker, Ruscus extract, and their combination on increased microvascular
      permeability induced by histamine. Experiments were performed on male hamsters;
      30 min after completion of the cheek pouch preparation, fluorescein-labeled
      dextran (molecular weight 150,000) was given intravenously (i.v.). Histamine,
      applied topically, increased the number of fluorescent vascular leakage sites
      from postcapillary venules, evidence of an increase in macromolecular
      permeability, which was quantified by ultraviolet light microscopy as the number
      of leaky sites in the prepared area. Prazosin (alpha 1-adrenoceptor antagonist),
      diltiazem (calcium blocker), and Ruscus extract applied topically dose
      dependently inhibited the macromolecular permeability-increasing effect of
      histamine. Rauwolscine (alpha 2-adrenoceptor antagonist), also applied topically,
      had no effect on histamine-induced permeability increase. Inhibition of the
      histamine-induced permeability increase evoked by Ruscus extract could be blocked
      by prazosin and by diltiazem but not by rauwolscine. These results indicate that
      any variation in the transmembrane flux of calcium impairs formation of
      microvascular leaky sites by histamine. Our results show that Ruscus extract has
      a protective effect against the leakage of FITC-dextran in hamster cheek pouch
      after administration of histamine that is modulated by calcium and selectively by
      alpha 1-adrenoceptors.

PMID- 7526064
TI  - Ischemic and nonischemic tissue concentrations of felodipine after coronary
      venous retroinfusion during myocardial ischemia and reperfusion: an experimental
      study in pigs.
AB  - Tissue and plasma concentrations of felodipine, a dihydropyridine (DHP) calcium
      antagonist, retroinfused through the coronary venous system were studied in 27
      pigs. The animals underwent 45-min myocardial ischemia followed by 4-h
      reperfusion. Felodipine (7 nmol/kg body weight) was administered in the coronary
      vein for 30 min, 5 min before reperfusion. Concentrations of felodipine in the
      ischemic and nonischemic myocardium and in plasma were determined by gas
      chromatography. In the ischemic area, felodipine concentration at start of
      reperfusion was 304 +/- 285, 171 +/- 160, and 52 +/- 47 nmol/kg (mean +/- SD) in
      the subepicardial, midmyocardial, and subendocardial layer, respectively.
      Corresponding concentrations in the nonischemic area were 15 +/- 13, 17 +/- 14,
      and 16 +/- 15 nmol/kg (p < 0.05 vs. ischemic area). Subepicardial concentration
      was highest at start of reperfusion, whereas concentrations in other layers
      peaked at the end of retroinfusion. The transmural concentration gradient of
      felodipine in the ischemic area decreased progressively during the reperfusion
      period. The nonischemic tissue concentration increased slightly during the
      reperfusion period. The plasma concentration was very low throughout the study
      (peak = 3.2 +/- 1.4 nM at 30 min). Coronary venous retroinfusion of felodipine
      resulted in profound accumulation of the drug, specifically in ischemic
      myocardium. The plasma concentration was low and did not affect systemic
      hemodynamics. Coronary venous retroinfusion is considered an advantageous
      technique for selective drug delivery.

PMID- 7526063
TI  - Cobalt contraction of vascular smooth muscle is calcium dependent.
AB  - We examined the mechanism by which cobalt causes contraction of vascular smooth
      muscle (VSM), determining whether contractile response of VSM from normotensive
      and hypertensive rats differed. Contraction of rings of rat thoracic aorta from
      normotensive Wistar-Kyoto rats (WKY) and hypertensive spontaneously hypertensive
      stroke-prone rats (SHRSP) in response to addition of cobalt chloride to the
      muscle bath was recorded. Threshold contraction occurred at 3 microM; maximum
      contraction occurred at 100 microM. There was no difference between rings from
      WKY and SHRSP in sensitivity or maximum response to cobalt. No contractile
      response occurred when cobalt was added to a calcium-free physiologic salt
      solution (PSS) to which 1.0 mM EGTA had been added. When no EGTA was added to the
      PSS, cobalt caused a contraction 20% as great as that observed in calcium
      containing physiologic salt solution, but this small contraction was eliminated
      after intracellular sequestration of calcium had been prevented by treatment of
      the rings with cyclopiazonic acid (3 x 10(-4) M). A concentration-dependent
      contraction occurred when calcium was added back to the bath in the presence of
      cobalt. The contraction in response to this addition of calcium did not differ
      between rings from WKY and SHRSP. Threshold concentrations of cobalt produced
      marked potentiations of contractile responses to either norepinephrine (NE) or
      KCl. We conclude that cobalt causes contraction by activating both voltage
      sensitive and receptor-operated calcium channels in the plasma membrane. Cobalt
      also caused release of intracellularly sequestered calcium. There was no
      difference between the responses to cobalt of VSM from WKY and SHRSP.

PMID- 7526065
TI  - Felodipine versus placebo in stable effort-induced angina pectoris in patients
      inadequately controlled with metoprolol--a dose-finding study.
AB  - We compared the antianginal and antiischemic effect and tolerability of four
      different doses of felodipine extended-release (ER) tablets with placebo in
      patients with stable effort-induced angina pectoris treated with beta-blocker
      [metoprolol controlled release (CR) 100 mg once daily, o.d.]. Seventy-five
      patients were enrolled in the study. At the end of a 2-week single-blind period,
      all patients performed two exercise tests. If total exercise time did not vary by
      > 15% between the two tests and both tests were limited by anginal discomfort and
      concomitant ST depression of at least 1 mm, the patients were randomized to
      double-blind treatment (66 patients). Each patient received three of the
      following treatments: felodipine 2.5, 5, 10, or 20 mg, or placebo. The treatments
      were given o.d. in a cross-over, balanced incomplete block design with three of 3
      week treatment periods. Exercise tests were performed 12 and 24 h after dose
      intake at the end of each treatment period. Fifty-nine patients completed the
      study. Twelve hours after dose administration, 10 and 20 mg felodipine increased
      time to onset of anginal pain by 60 and 63 s on the average, respectively, as
      compared with placebo (p = 0.001). Time to 1-mm ST depression was prolonged by 29
      s after 10 mg (p = 0.14) and by 30 s after 20 mg (p = 0.13) felodipine. Time to
      end of exercise was increased by 28 s (p = 0.07) and 15 s (p > 0.20),
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526062
TI  - Effect of taurine and methionine on sarcoplasmic reticular Ca2+ transport and
      phospholipid methyltransferase activity.
AB  - Perfusion of rat hearts with buffer containing 300 microM L-methionine led to a
      decrease in Ca(2+)-induced Ca2+ release in sarcoplasmic reticulum (SR) but an
      increase in calcium-independent Ca2+ release from junctional SR. These effects of
      L-methionine were not altered by exposure of the hearts to high levels of
      extracellular taurine, but changes in the size of the intracellular taurine pool
      appear to modulate calcium transport in SR through two mechanisms. First,
      millimolar concentrations of taurine can directly promote release of calcium from
      45Ca(2+)-loaded junctional SR vesicles. Second, taurine serves as an inhibitor of
      SR phospholipid methyltransferase, an enzyme that appears to be responsible for
      methionine-mediated loss in Ca(2+)-induced Ca2+ release activity and promotion of
      Ca(2+)-independent Ca2+ release. The data imply that modulation of the
      intracellular taurine pool may affect cellular calcium homeostasis and myocardial
      contractile function. This may be important in development of the cardiomyopathy
      linked to taurine deficiency.

PMID- 7526066
TI  - Effect of NKH477, a new water-soluble forskolin derivative, on arterial
      ventricular coupling and mechanical energy transduction in patients with left
      ventricular systolic dysfunction: comparison with dobutamine.
AB  - We examined the effects of a novel water-soluble forskolin derivative, NKH477
      (0.5 microgram/kg/min), on arterial-ventricular (A-V) coupling and mechanical
      energy transduction from heart to circulatory bed in comparison with those of
      dobutamine (3 micrograms/kg/min) in 8 patients with left ventricular (LV)
      systolic dysfunction using a conductance catheter method. A-V coupling was
      assessed as the ratio of the effective arterial elastance (E(a)) to the slope of
      the end-systolic pressure-volume relation (ESPVR) (E(max), left ventricular
      contractility index), and the ratio of mechanical energy transduction was
      obtained as the fraction of PV area (PVA) comprised of stroke work (SW). E(max)
      (2.59 mm Hg/ml/m2), E(a)/E(max) (1.62), and SW/PVA (0.58) were impaired in
      control contractile state. NKH477 increased Emax to the same extent as
      dobutamine. E(a) decreased with NKH477 but not with dobutamine. As a consequence,
      the decrease in E(a)/E(max) with NKH477 was greater than that with dobutamine (52
      vs. 47%, p < 0.05); the increase in SW/PVA with NKH477 was also greater than that
      with dobutamine (28 vs. 21%, p < 0.05). These findings suggest that NKH477 may be
      a superior alternative to dobutamine in A-V coupling and mechanical energy
      transduction in patients with LV systolic dysfunction.

PMID- 7526067
TI  - Angiotensin-converting enzyme inhibition by hydroxamic zinc-binding idrapril in
      humans.
AB  - The new angiotensin-converting enzyme (ACE) inhibitor idrapril acts by binding
      the catalytically important zinc ion to a hydroxamic group. We investigated its
      pharmacodynamic and pharmacokinetic properties in 8 healthy men: Increasing doses
      of 1, 5, and 25 mg idrapril as well as placebo or 5 mg captopril were
      administered intravenously (i.v.) at 1-week intervals. Six of the subjects
      received 100 mg idrapril orally (p.o.) last, and two ingested oral placebo as a
      double-blind control. Blood pressure (BP) and heart rate (HR) remained unchanged.
      No serious side effects were observed. ACE inhibition in vivo was evaluated by
      changes in the ratio of specifically measured plasma angiotensin II (AngII) and
      AngI concentrations determined by high-performance liquid
      chromatography/radioimmunoassay (HPLC/RIA) techniques. Plasma ACE activity in
      vitro was estimated by radioenzymatic assay; it was suppressed by > or = 93% at
      15 min after injection of 25 mg idrapril or 5 mg captopril and by 96% 2 h after
      idrapril intake. Mean AngII levels were decreased dose dependently at 15 min
      after idrapril injections. At the same time, plasma renin activity (PRA) and AngI
      increased according to the doses. The AngII/AngI ratio was clearly related to
      plasma idrapril levels (r = -0.88, n = 60). Oral idrapril inhibited ACE maximally
      at 1-4 h after dosing, when < 7% of initial ACE activity was observed in vitro
      and in vivo. Idrapril is a safe and efficient ACE inhibitor in human subjects. It
      is well absorbed orally. Besides having a slightly slower onset of action,
      idrapril has pharmacodynamic effects comparable to those of captopril.

PMID- 7526068
TI  - Effects of N omega-monomethyl-L-arginine on short-term RR interval and systolic
      blood pressure oscillations.
AB  - The role of endothelium-derived nitric oxide (EDNO) in short-term regulation of
      RR interval and arterial blood pressure (BP) in conscious rats was studied with N
      omega-monomethyl-L-arginine (L-NMMA). RR interval and systolic BP (SBP)
      variability was investigated by spectral analysis procedures. L-NMMA infused
      intravenously (i.v.) at 1.2 mg/kg/min elicited a clear increase in blood pressure
      (BP), RR interval (RRI), and respiratory rate. The main spectral modifications
      observed during L-NMMA infusion were (a) an increase in power of lower frequency
      (LF, 0.02-0.20 Hz) systolic BP (SBP) oscillations, (b) a decrease in the power of
      middle frequency (MF, 0.20-0.60 Hz), SBP oscillations, (c) an increase in the
      power of respiratory (high-frequency, HF) RR oscillations, and (d) an increase in
      the SBP-RR correlation in the LF band. These results suggest that L-NMMA infusion
      induced a rearrangement in the lower frequency oscillations of SBP, in which a
      decrease in sympathetic activity appears to be involved. The increase in HF
      oscillations of the RR interval appears to be a consequence of the increase in
      vagal activity in response to the increase in SBP induced by L-NMMA infusion. The
      suggested autonomic nervous system alterations could account for the increase in
      the SBP-RRI correlation in the LF band after L-NMMA administration.

PMID- 7526069
TI  - Role of L-type calcium channels on stimulated calcium influx and on proliferative
      activity of human coronary smooth muscle cells.
AB  - Dihydropyridine (DHP) calcium channel blockers are widely used in treatment of
      coronary artery disease. To evaluate the specific role of L-type calcium channels
      in the antianginal and possibly antiatherosclerotic properties of DHP inhibitors,
      we examined the effects of a 1,4-DHP agonist and antagonist on angiotensin II
      (ANG II)- and serum-stimulated calcium influx and proliferation of human coronary
      smooth muscle cells (cSMC). Fluorometry of fura-2 was used to measure changes in
      free cytosolic Ca2+ concentration ([Ca2+]i) in cSMC after short- and long-term
      pretreatment with the calcium agonist Bay K 8644 or the antagonist nitrendipine,
      respectively. Proliferative activity was quantified during exponential growth in
      serum-supplemented medium with or without both DHPs. Short- and long-term
      pretreatment with Bay K 8644 increased basal [Ca2+]i significantly in resting
      cells and augmented ANG II- and serum-induced sustained [Ca2+]i responses.
      Concordantly, proliferation rate was increased. In contrast, nitrendipine had no
      significant effect on basal or stimulated [Ca2+]i after short-term treatment, but
      decreased [Ca2+]i after 24-h incubation, attenuated the plateau phase of ANG II-
      and serum-evoked [Ca2+]i transients, and reduced proliferative activity of these
      cells. The results indicate that 1,4-DHPs modulate ANG II- and serum-induced Ca2+
      influx in cSMC. Thus, L-type calcium channels may contribute to [Ca2+]i
      transients evoked by ANG II and serum. Moreover, the modulating effects of both
      DHPs on proliferative activity suggest involvement of DHP-sensitive calcium
      channels. Calcium influx through L-type channels may be one of the mechanisms
      that determine responsiveness to vasoconstrictors and proliferative activity of
      human cSMC.

PMID- 7526070
TI  - Beta-adrenoceptor antagonism and the hyperthyroid rat heart.
AB  - beta-Adrenoceptor antagonists such as propranolol and atenolol ameliorate the
      symptoms of human hyperthyroidism. We wished to define whether the cardiac
      changes of hyperthyroidism are attenuated by treatment with the beta-adrenoceptor
      antagonist atenolol. Rats were treated with triiodothyronine (T3) [1 mg/kg/day
      subcutaneously (s.c.) for 14 days] together with oral atenolol (100 mg/day on
      days 8-14); physiological parameters, inotropic and chronotropic responses in
      isolated cardiac tissues to compounds that increase intracellular cyclic AMP, and
      ventricular beta 1- and beta 2-adrenoceptors were measured. Administration of T3
      produced marked hyperthyroidism, leading to increased metabolism, cardiac
      hypertrophy, tachycardia, hypertension, marked decrease in or loss of positive
      inotropic responses to calcium chloride, norepinephrine (NE), forskolin, and
      theophylline and increased ventricular beta 1- and beta 2-adrenoceptor density.
      Atenolol treatment of hyperthyroid rats attenuated the increases in heart rate
      (HR), rectal temperature, and O2 consumption but did not alter cardiac
      hypertrophy, hypertension, decreased positive inotropic responses or increased
      beta-adrenoceptor density. We conclude that beta-adrenoceptor antagonists produce
      only limited changes in hyperthyroidism-induced cardiovascular responses;
      furthermore, beta-adrenoceptor antagonists are unlikely to attenuate the
      cardiovascular risk factors of hyperthyroidism.

PMID- 7526071
TI  - Impact of isradipine on contractile performance, metabolism, and coronary
      resistance studied in isolated rat hearts.
AB  - In anesthetized dogs, isradipine has been reported to induce peripheral
      vasodilation and increase cardiac output (CO) and myocardial contractility,
      whereas myocardial oxygen consumption (MVO2) decreases, suggesting that
      isradipine may increase overall metabolic efficiency of the ventricle of intact
      animals. Whether isradipine has any direct myocardial effects that could cause
      intrinsic increase in metabolic efficiency or whether the observation relates to
      favorable isradipine-induced changes in hemodynamic loading conditions is not
      known. Therefore, we determined the direct myocardial effects of isradipine on
      contractile strength and metabolic efficiency in isolated rat heart. Isolated
      crystalloid perfused rat hearts were instrumented for measurement of ventricular
      pressure, volume, and MVO2. Isradipine decreased developed pressure (DP) and MVO2
      in a concentration-dependent manner; at 32 nM irradipine, both quantities were
      approximately 70% of their control values. Isradipine caused a downward shift of
      the end-systolic pressure-volume relation (ESPVR) and in the relation between
      ventricular work (indexed by pressure-volume area, PVA) and MVO2, indicating that
      for any given amount of total mechanical work performed, the rat heart consumed
      less O2 during administration of isradipine than under control conditions.
      However, the magnitude of the downward shift of this relation was nearly
      identical to that observed in a separate group of hearts in which we decreased
      contractility by decreasing the perfusate calcium concentration. Thus, isradipine
      does not appear to have a contractility-independent effect on myocardial
      efficiency.

PMID- 7526072
TI  - In vivo activity of bleomycin incorporated with biodegradable poly-d,l-lactic
      acid and implanted in the mediastinum of dogs.
AB  - The possible usefulness of bleomycin incorporated with biodegradable poly-d, l
      lactic acid (BLM-PLA) for targeting chemotherapy for esophageal cancer was
      studied in vivo. Local levels of BLM after administration were compared with
      those after injection of BLM-SOL, an aqueous solution of BLM. BLM-PLA or BLM-SOL
      was administered into the upper mediastinum under a right thoracotomy in 36
      mongrel dogs. On days 10, 20, and 30 after administration, connective tissues,
      lymph nodes, lung, liver, kidney, and spleen were removed, and BLM activity was
      measured. High activity of BLM was detected for 30 days after BLM-PLA
      administration in both the connective tissues and the lymph nodes, compared with
      BLM-SOL administration. BLM activity was low in the other organs after BLM-PLA
      administration. BLM in the blood was significantly lower after administration of
      BLM-PLA than BLM-SOL. The results indicate that BLM-PLA may become a useful tool
      in targeting chemotherapy for esophageal cancer.

PMID- 7526073
TI  - Structural similarities between myelin and hydrophobic surfactant associated
      proteins: protein motifs for interacting with bilayers.
AB  - A group of predicted structural similarities exist between the hydrophobic
      pulmonary surfactant protein SP-B and SP-C and the hydrophobic proteins of
      myelin, either the myelin basic protein and the proteolipid protein of central
      nervous system myelin, or the P0 protein of peripheral myelin. These similarities
      include, among other factors, the charge density, post-translational modification
      by fatty acids, some potential periodicity in primary structure and an overall
      hydrophobicity. The similarities suggest that these proteins might have similar
      means of interacting with each other and with lipid bilayers in their respective
      biological systems.

PMID- 7526074
TI  - Modeling a non-inactivating delayed rectifier cardiac current using voltage clamp
      data.
AB  - This paper describes a new parameter estimation method applicable to experimental
      voltage-clamp records. The method is based on the Hodgkin-Huxley (HH)
      representation of a generic non-inactivating delayed rectifier current (IK) which
      can be assimilated to the delayed rectifier potassium current of cardiac cells.
      The model involves a single gating variable of activation (chi) of degree (lambda
      chi). Its parameters include the voltage-dependent steady-state characteristic
      (chi infinity), time constant tau chi, the degree lambda chi as a positive
      integer, and the maximal conductance gK. The method is based on linear
      optimization. It implements a series of least-squares minimization steps to
      calculate a first estimate of each model parameter, followed by global
      minimization to obtain final estimates. The required data, in the form of ionic
      current responses, correspond to standard voltage-clamp protocols. The effects of
      noise are minimized by avoiding the use of the time derivative of IK in the
      calculations. Simulated voltage-clamp data using either a HH model or a five
      state Markov chain (MC) model served two purposes: (i) to test the performance of
      the HH parameter estimation method, and (ii) to study the suitability of the HH
      model to reproduce data generated by models other than HH. A nominal MC model was
      obtained by fitting its current responses to those of the HH model. Rate
      constants of the nominal MC model were then modified and voltage-clamp current
      responses were generated. Excellent results were obtained with HH and nominal MC
      data. Data sets generated by a 20% change in the rate constants of the nominal MC
      model showed that the closed-state rate constants have only a limited influence
      on the HH parameter estimates, whereas changes in the closed-to-open rate
      constants produce substantial effects. Nevertheless, a given MC data set can be
      fitted quite closely by a HH model. In the light of these simulation results it
      is indicated that an hybrid HH-MC representation of IK data would be more
      flexible than a straight HH model by removing some of the constraints between the
      rate constants, and less cumbersome than a straight MC model by substantially
      reducing the number of parameters to be estimated.

PMID- 7526075
TI  - On the conformational stability of oligonucleotide duplexes and tRNA molecules.
AB  - Thermodynamic experiments provide a wealth of data about the conformational
      stability, viz., the free energy difference (delta G) between folded and unfolded
      states of DNA/RNA duplexes. However, there is no acceptable view about how the
      various non-covalent forces contribute individually to the observed stability. In
      particular, the role of the hydrophobic force is not clearly known. In this paper
      we quantitatively enumerate the stability factors, hydrogen bonding, base
      stacking, van der Waals, electrostatic, and hydrophobic interactions from the
      knowledge of the crystal structures of 15 DNA/RNA duplexes and two tRNA
      molecules, and translate them into free energy contributions to the stability of
      nucleic acid systems. Taking the experimental delta G values and computed
      component free energy terms for a set of duplexes, we set up multiple regression
      equations to predict their stabilities. After back-check and validity tests, we
      apply this model to predict delta G values for a large number of duplexes and two
      tRNA molecules (tRNAphe and tRNAasp). There is excellent agreement between the
      theoretical predictions and experimental observations. The considered duplexes
      with four to 16 base-pairs and the tRNA molecules have delta G values in a narrow
      range, 5-20 kcal mol-1, a range seen in a variety of globular proteins. There is
      no relationship between delta G and N, the number of nucleotides in the molecule.
      Base-stacking, hydrogen bonding and van der Waals factors contribute
      significantly, whereas hydrophobic and electrostatic factors contribute,
      respectively, marginally and minimally. The major factor which gives sequence
      specificity is base-stacking. The new set of atomic solvation parameters (ASPs)
      derived to estimate hydrophobic free energy brings to light the dangers of using
      already available ASPs, which emphasize the role of the hydrophobic factor
      unrealistically.

PMID- 7526076
TI  - Salvia divinorum and salvinorin A: new pharmacologic findings.
AB  - The diterpene salvinorin A from Salvia divinorum (Epling and Jativa-M), in doses
      of 200-500 micrograms produces effects which are subjectively identical to those
      experienced when the whole herb is ingested. Salvinorin A is effectively
      deactivated by the gastrointestinal system, so alternative routes of absorption
      must be used to maintain its activity. Traditionally the herb is consumed either
      by chewing the fresh leaves or by drinking the juices of freshly crushed leaves.
      The effects of the herb when consumed this way depend on absorption of salvinorin
      A through the oral mucosa before the herb is swallowed.

PMID- 7526077
TI  - Testing garlic for possible anti-ageing effects on long-term growth
      characteristics, morphology and macromolecular synthesis of human fibroblasts in
      culture.
AB  - The beneficial effects claimed for the use of garlic as a nutritional supplement
      include detoxification, antioxidation, antifungal activity, antibacterial
      activity, tumour suppression and, possibly, anti-ageing and rejuvenating effects.
      We have used the Hayflick system of cellular ageing in culture in order to test
      garlic for its anti-ageing effects on long-term growth characteristics,
      morphology and macromolecular synthesis of human skin fibroblasts. Our results
      show that an addition of garlic extract into the normal cell culture medium can
      support serial subculturing for over more than 55 population doublings in 475
      days, and that this treatment has some youth-preserving, anti-ageing and
      beneficial effects on human fibroblasts in terms of maximum proliferative
      capacity and morphological characteristics. In comparison, similar or lesser
      doses of garlic extracts are growth inhibitory for cancerous cells that could not
      be grown over longer periods in the presence of garlic. To our knowledge, this is
      the first report of the effects of garlic on the long-term growth characteristics
      and macromolecular synthesis of normal human skin cells, the results of which
      have applications for both anti-ageing and anti-cancer research.

PMID- 7526079
TI  - Induction of cell surface interleukin 2 receptor alpha chain expression on non-T
      lymphoid leukemia cells.
AB  - We examined nine cases of adult non-T lymphoid leukemia to investigate the cell
      surface inducibility of interleukin 2 receptor alpha chain (IL-2R alpha) and beta
      chain (IL-2R beta) after in vitro culture with and without recombinant human
      interleukin-1 beta (rhIL-1 beta). Induction of IL-2R alpha was observed in four
      of six cases with precursor B-cell acute lymphoblastic leukemia (pre-B ALL) and
      in all of three cases with B-cell mature lymphoid neoplasm (two chronic
      lymphocytic leukemia and one leukemic phase of non-Hodgkin's lymphoma). All of
      the IL-2R alpha-inducible cases could express this spontaneously even without
      rhIL-1 beta, while IL-2R beta did not appear on leukemic cells from any of the
      cases tested. IL-2R alpha-inducible pre-B ALL cases displayed stem cell antigen
      CD34 and induced myeloid-associated antigen CD13 simultaneously. These results
      suggest that IL-2R alpha but not IL-2R beta is easily inducible in certain cases
      of mature B-cell lymphoid neoplasm and pre-B ALL with immature characteristics.

PMID- 7526078
TI  - Lymphokine-activated killer cytotoxicity and lymphocyte subpopulations in
      patients with acute leukemia.
AB  - In this report we investigated lymphokine-activated killer (LAK) cytotoxicity and
      lymphocyte subpopulations of peripheral blood mononuclear cells (PBMCs) of
      patients with acute leukemia in complete remission after chemotherapy or
      autologous bone marrow transplantation (ABMT) and of normal donors. A positive
      linear correlation was found between the percentage of spontaneous LAK activity
      and that of lymphocyte subpopulations with phenotypes CD56+, CD3-CD8+ CD3-CD56+
      and CD3-CD57+ in both groups of patients. A 3-day culture with IL-2 produced an
      up-regulation in the expression of the CD25, CD69, and HLA-DR markers
      proportional to the LAK cytotoxicity levels generated in the culture.
      Determination of percentages of spontaneous and in vitro generated LAK activity
      as well as of the above mentioned phenotypic markers contribute to the analysis
      of the process of LAK activation in patients with acute leukemia and may also be
      useful in those cases in which immunotherapy with IL-2 and/or LAK cells is
      anticipated.

PMID- 7526080
TI  - Treatment of graft failure after bone marrow transplantation.

PMID- 7526081
TI  - Semiquantitative analysis of in-situ hybridization results using IMAGE software:
      a rapid method for counting reduced silver grains over mRNA-positive cells.
AB  - The advent of microcomputers has brought about a revolution in the computing
      power available to the average user. Image analysis is a very resource-intensive
      process, making great demands on computing power, memory, and display
      capabilities of most computers. Thus, in the past, dedicated, single-use hardware
      and software had to be custom made for environments requiring image analysis. We
      present here an easy-to-use image analysis protocol available to most users with
      a Macintosh II series computer and access to IMAGE (a public domain image
      analysis program). The protocol allows for semi-quantitation of silver grains
      over cells used in the interpretation of in-situ hybridization results. We show
      that the method provides a quick and reliable means of counting grains over mRNA
      positive cells in an automated fashion. We also provide evidence that the method
      can be used to detect differences between experimental treatments.

PMID- 7526082
TI  - Differential labeling of converging afferent pathways using biotinylated dextran
      amine and cholera toxin subunit B.
AB  - We report a new technique for 2-tracer anterograde labeling that permits
      unequivocal identification of the differentially labeled projections in the same
      section. One pathway is labeled with biotinylated dextran amine and is visualized
      as a black to dark gray diaminobenzidine (DAB)-cobalt precipitate by an avidin
      biotinylated peroxidase reaction. The other pathway is labeled with cholera toxin
      subunit B and is visualized as a reddish-brown reaction product using DAB without
      cobalt as the substrate for peroxidase immunohistochemistry. To maintain serial
      order, sections can be processed mounted on slides without any loss of
      sensitivity for either tracer.

PMID- 7526083
TI  - Combined anterograde tracing with biotinylated dextran-amine, retrograde tracing
      with fast blue and intracellular filling of neurons with lucifer yellow: an
      electron microscopic method.
AB  - In order to determine the presence of synaptic connectivity between fibres
      originating from a specific source and neurones with a known morphology and known
      fibre projection, we have introduced a method for electron microscopy that
      combines three techniques: retrograde fluorescent tracing, anterograde tracing
      using biotinylated dextran-amine and intracellular injection of Lucifer Yellow
      (LY) in lightly fixed brain slices. Neurones in the rat entorhinal cortex that
      project to the infralimbic cortex and that might be in synaptic contact with
      fibres originating in the dorsal subiculum served as a model. After surgical
      application of the tracers and a survival period enabling transport, the brain
      was fixed and vibratome slices 300 microns thick were prepared in which
      retrogradely labelled cells were intracellularly injected with LY. This substance
      and the transported biotinylated dextran-amine were converted into different
      electron-dense labels. First, LY immunocytochemistry was conducted, then followed
      by silver-gold enhancement of the immunoprecipitate. Subsequently, the tissue
      sections were treated with an avidin-biotin-horseradish peroxidase complex and
      subjected to a diaminobenzidine-peroxide reaction. This protocol resulted in
      labelling of biotinylated dextran-amine-positive fibres and terminals that could
      easily be differentiated from the LY-positive neuronal elements and also showed
      well preserved ultrastructural detail.

PMID- 7526084
TI  - A simple method to improve the reliability of iontophoretic administration of
      tracer substances.
AB  - Microiontophoresis is a widely used technique for depositing tracer materials
      into the central nervous system for neuroanatomical experiments. However, the
      reliability of iontophoretic injection is often less than optimal. Coating the
      lumen of glass micropipettes with silicone to reduce surface tension reduced the
      incidence of failure for iontophoretic deposition of wheat germ agglutinin
      horseradish peroxidase (WGA-HRP) from 40% to zero. Similar results were observed
      with other tracer substances. Siliconizing the internal surface of glass
      micropipettes can significantly improve the reliability of iontophoretic
      deposition.

PMID- 7526086
TI  - APO-1 (CD95) mediated apoptosis in human T-ALL engrafted in SCID mice.
AB  - The monoclonal antibody anti-APO-1 induces apoptosis upon triggering the cell
      surface molecule APO-1 (CD95), a novel member of the tumor necrosis factor/nerve
      growth factor receptor superfamily. We tested the efficacy of APO-1 mediated
      apoptosis in a model system of human leukemia in SCID mice. T-ALL cells recovered
      from SCID mice were sensitive towards anti-APO-1 mediated apoptosis when tested
      in vitro. In vivo, treatment of leukemia-bearing SCID mice with anti-APO-1
      induced programmed cell death in a substantial fraction of T-ALL cells, thus
      leading to significantly prolonged survival. Anti-APO-1 treatment, however,
      failed to completely eliminate all leukemic cells. This may be due to resistance
      towards anti-APO-1 mediated apoptosis in a fraction of T-ALL cells. Thus,
      identification of cellular programs which determine sensitivity and resistance
      towards apoptosis may provide new perspectives for rational therapeutic
      interventions.

PMID- 7526085
TI  - Assay of neuronal nitric oxide synthase by HPLC determination of citrulline.
AB  - Biological membranes from different tissue sources were incubated for nitric
      oxide synthase (NOS) activity under standard conditions at 20 degrees C and
      compared with rat cerebellar cytosol. NOS activity was monitored as the formation
      of L-citrulline from L-arginine. Samples were purified on Amprep CBA cation
      exchange minicolumns prior to derivatization with o-phthaldialdehyde (OPA) and
      HPLC analysis. The OPA derivatives of L-citrulline and L-arginine eluted well
      separated within 15 min during isocratic elution at room temperature. A linear
      relation between peak height and quantity of L-citrulline was seen down to the
      detection limit at 0.1 pmol L-citrulline. Formation of L-citrulline was
      measurable in rat cerebellar cytosol as well as in preparations not previously
      assayed for NOS activity, including rat colon, cat oesophagus and crayfish
      (Pacifastacus leniusculus) brain. The method provides a sensitive and non
      radioactive method for assaying NOS activity in small tissue samples and in
      tissues with low to moderate levels of NOS activity.

PMID- 7526088
TI  - FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable
      protocol for the treatment of 'poor risk' acute myeloid leukemias.
AB  - Twenty-eight patients with poor prognosis acute myeloid leukemia (AML) received
      therapy with two courses of fludarabine 30 mg/m2/day + ara-C 2 g/m2/day (days 1
      5) and G-CSF 5 mg/kg/day (FLAG) (from day 0 to polymorphonuclear recovery).
      Eighteen patients were considered 'refractory' (eight primarily resistant, five
      relapsing within 6 months of initial remission, or at a second relapse; five
      relapsing after an autologous bone marrow transplantation procedure. Ten cases
      were defined 'secondary' AML (diagnosis of AML made after a preexisting diagnosis
      of: myelodysplastic syndrome: five cases; myelodysplastic syndrome after therapy
      for breast cancer: one case; previously untreated, and concomitant, non-Hodgkin's
      lymphoma: two cases; Hodgkin's disease treated with chemoradiotherapy: one case).
      Overall, 15 patients (58%) achieved a complete remission (CR). Two patients died
      of infection during induction, and 11 had resistant disease. Analyzing the data
      in relation to selected host and disease characteristics, the response varied
      widely. The highest CR rates (89%) were obtained in secondary AML; in particular,
      two cases of 'second-primary' (concomitant with low-grade non-Hodgkin's lymphoma)
      AML obtained CR for both diseases. Refractory AML differed widely for response:
      high CR rate (75%), although with short mean CR duration for primary resistance
      AML, and very poor response (11% CR) for relapsed (early, second, after ABMT)
      cases. Interestingly, a slow kinetic of leukemic growth in vivo before FLAG
      administration was significantly related to the response and outcome (p =
      0.0002). Hematological and nonhematological toxicities were acceptable. In
      conclusion, the FLAG regimen has significant antileukemic activity and acceptable
      toxicity especially in secondary AML, both with and without coexisting lymphoid
      malignancy.

PMID- 7526089
TI  - Immunophenotypic differences between putative hematopoietic stem cells and
      childhood B-cell precursor acute lymphoblastic leukemia cells.
AB  - Acute leukemia cells express myeloid, B-lymphoid and T-lymphoid lineage specific
      antigens. Many acute leukemias express the hematopoietic progenitor cell antigen
      CD34. Three proposed models of the normal human hematopoietic stem cell include
      CD34+ Thy-1low Lin-, CD34+ CD38-, and CD34+ HLA-DR-. The patterns of expression
      of CD34, Thy-1, CD38, HLA-DR, and multiple lineage-specific antigens on 49
      consecutive pediatric B-cell precursor acute lymphoblastic leukemia (ALL) cases
      submitted for immunophenotyping (36 at first diagnosis, 13 at relapse) were
      analyzed. CD34+ expression was observed in 67% of the cases. CD34+ expression
      correlated with Thy-1low expression and expression of myeloid antigens (p < 0.001
      and < 0.025, respectively). The CD34+ Thy-1low phenotype was observed in 65% of
      the cases; the CD34+ CD38- or CD34+ HLA-DR- phenotypes were observed in only
      three cases. Examples of heterogeneous expression of CD34 and Thy-1 were found in
      six cases, but CD38 expression was always bright and homogeneous in all positive
      cases. The data from this analysis indicates that the CD34+ CD38- or CD34+ HLA-DR
      phenotypes would be more useful than the CD34+ Thy-1low phenotype for
      distinguishing normal hematopoietic stem cells from leukemic cells in childhood B
      cell precursor ALL.

PMID- 7526090
TI  - P-glycoprotein (P-170) and CD34 expression in adult acute myeloid leukemia (AML).
AB  - We investigated the prognosis value of CD34 and P-170 expression in blast cells
      of adult patients affected by de novo acute myeloid leukemia (AML). CD34 antigen
      was analyzed by indirect immunofluorescence (IFI) and alkaline phosphatase
      labeled streptavidin biotine (AP-LSAB) in 62 patients (median age: 51 years). P
      170 expression was determined by AP-LSAB in 51 cases using JSB1 and C219
      monoclonal antibodies. All patients were treated with conventional chemotherapy
      induction regimen. Follow-up was from 6 to 79 months. Complete remission (CR)
      rate was not statistically different between CD34+ and CD34- patients (67 vs.
      84%, p = 0.2). The duration of CR and survival were not influenced by CD34
      expression. Karyotype abnormalities were more frequent among MDR+ patients (65
      vs. 21%, p < 0.01). CR rate was statistically lower in MDR+ patients as compared
      to MDR- patients (63 vs. 96%, p = 0.01). Median disease-free survival (DFS) was
      shorter for MDR+ patients but the difference was not significant (5 vs. 10
      months, p = 0.09). Patients who were positive for both parameters CD34 and P-170,
      had a poor prognosis with a 50 vs. 100% CR rate for CD34/P-170 negative patients,
      (p = 0.002), a lower median DFS (3 vs. 12 months, p = 0.01) and overall survival
      (OS) (3 vs. 14.5 months, p = 0.01). Results of cytogenetic analysis did not
      influence CR rate but the relapse rate was higher, although not significant, for
      the patients with unfavorable karyotype (63 vs. 33%). The seven CD34+/MDR+
      patients with poor prognosis karyotype had a statistically lower CR rate, median
      DFS and OS than the 7 CD34-/MDR- patients with normal or favorable karyotype (CR:
      29% vs. 100%, p = 0.02), (DFS: 3 vs. > 12 months, p = 0.01), (OS: 4 vs. > 12
      months, p = 0.02). Our data indicate that P-170 but not CD34 expression is
      predictive for a lower CR rate. The identification of a bad prognosis subgroup of
      CD34+/MDR+ AML patients (and especially those with poor prognosis karyotype) has
      to be confirmed on larger series using uniform methodology.

PMID- 7526091
TI  - Association of GP51 expression and persistent CD5+ B-lymphocyte expansion with
      lymphomagenesis in bovine leukemia virus infected sheep.
AB  - Alterations in the circulating CD5+ B-lymphocyte population, in vitro GP51
      expression, and in vivo tax/rex expression that may precede lymphomagenesis were
      characterized prospectively in ten experimentally BLV-infected sheep. Infection
      with pathogenetic BLV resulted in a significant expansion of the circulating CD5+
      B-lymphocyte population in six infected sheep. Of the remaining four infected
      sheep that did not have persistently elevated CD5+ B-lymphocyte counts, three
      developed lymphoid neoplasia within 14 months post-inoculation. Neoplastic cells
      from two of these three sheep were CD5- B-lymphocytes, while cells from the third
      were CD5+ B-lymphocytes. In vitro GP51 expression was a consistent feature of
      circulating lymphocytes from all three sheep developing tumors, but high level
      tax/rex gene transcription was not detected in circulating lymphocytes prior to
      lymphomagenesis. Neither in vitro GP51 expression nor high level tax/rex gene
      transcription was associated with expansion of the CD5+ B-lymphocyte population
      in sheep with significantly elevated CD5+ B-lymphocyte counts. These observations
      indicate that BLV infection in sheep results in expansion of the circulating CD5+
      B-lymphocyte population, and that this expansion is not required for the
      subsequent development of BLV-associated lymphoid neoplasia.

PMID- 7526092
TI  - Direct detection of the Philadelphia chromosome in CD20-positive lymphocytes in
      chronic myeloid leukemia by tri-color immunophenotyping/FISH.
AB  - Six patients with previously diagnosed chronic myelogenous leukemia (CML) were
      studied by a tri-color immunophenotyping/FISH method for direct determination of
      the Philadelphia (Ph) chromosome in B and T lymphocytes. Two patients had
      involvement of CD20-positive lymphocytes. CD3-positive lymphocytes in all
      patients were negative for the Ph chromosome.

PMID- 7526087
TI  - Low-dose continuous subcutaneous infusion of granulocyte colony-stimulating
      factor for chemotherapy-induced neutropenia in acute myelogenous leukemia and its
      pharmacokinetics.
AB  - Granulocyte colony-stimulating factor (G-CSF) shortens the duration of
      chemotherapy-induced granulocytopenia in acute leukemia. G-CSF is administered by
      30-min intravenous infusion at a dose of 200 micrograms/m2/day or 5
      micrograms/kg/day in most studies. In this study, the efficacy of a reduced dose
      (33 micrograms/m2/day) of continuous subcutaneous infusion of G-CSF was compared
      with the effects achieved by 30-min intravenous infusion of the standard dose
      (200 micrograms/m2/day) in neutropenia after identical chemotherapy in seven
      patients with acute myelogenous leukemia who were in remission. The duration of
      granulocytopenia (< 0.5 x 10(9)/l), thrombocytopenia (< 50 x 10(9)/l); G-CSF
      administration and fever (> 38 degrees C) were 10.1 +/- 5.0 days, 16.5 +/- 9.3
      days, 16.6 +/- 7.4 days and 3.1 +/- 5.4 days for 33 micrograms/m2/day continuous
      subcutaneous infusion, and 10.7 +/- 6.8 days, 16.7 +/- 9.9 days, 16.1 +/- 7.6
      days and 2.0 +/- 2.5 days for 30-min intravenous infusion of the standard dose of
      G-CSF. In each parameter studied, there was no statistical difference between the
      two methods of G-CSF administration by paired t-test. The costs for G-CSF could
      be substantially reduced. In most patients, plasma G-CSF concentration rose to
      the highest level of 1.8-3.7 ng/ml 48-72 h after starting 33 micrograms/m2/day
      continuous subcutaneous infusion, and gradually decreased as the peripheral
      granulocyte count recovered, suggesting binding of G-CSF molecules to the
      specific receptors on the cells of granulocytic lineage.

PMID- 7526093
TI  - High levels of p26BCL-2 oncoprotein retard taxol-induced apoptosis in human pre-B
      leukemia cells.
AB  - In human leukemic cells clinically relevant concentrations of taxol have been
      demonstrated to induce the biochemical and morphologic hallmarks of apoptosis
      (Leukemia 1993;7:563-568). Since overexpression of the bcl-2 gene has been
      reported to retard apoptosis due to a variety of anticancer agents, we examined
      and compared taxol-induced intracellular microtubular bundling and apoptosis in
      pre-B human leukemia 697 cells and their counterparts which have been transfected
      with and overexpress cDNA derived from the bcl-2 gene. Treatment with 0.1 or 1.0
      mumol/l taxol for 24 h resulted in internucleosomal DNA fragmentation and
      morphologic features of apoptosis in 697 cells, but not in 697/BCL-2 cells.
      However, indirect immunofluorescent staining with anti-tubulin antibody revealed
      that taxol treatment produces stable microtubule bundles resistant to calcium
      mediated disassembly in 697, as well as 697/BCL-2 cells. In addition, taxol
      induced microtubule bundling was associated with a marked accumulation of the two
      cell types in the G2/M phase of the cell cycle. Following exposure to taxol, when
      697 cells were washed and kept in drug-free medium, they showed rapid onset of
      apoptosis followed by loss of cell viability and a decline in cell numbers. In
      contrast, identically treated 697/BCL-2 cells kept in drug-free medium remained
      in a growth arrested state, but showed little evidence of apoptosis for up to 4
      days. They eventually demonstrated features of apoptotic cell death and loss of
      viability between 5 and 7 days. This was not accompanied by a decrease in p26BCL
      2 levels. Anti-phosphotyrosine or anti-MAP kinase immunoblot analyses of proteins
      isolated from taxol-treated 697 and 697/BCL-2 cells failed to show any difference
      in tyrosine phosphorylation of cellular proteins. Therefore, our findings
      indicate that in 697/BCL-2 cells, high levels of p26BCL-2 significantly delay
      taxol-induced endonucleolytic internucleosomal DNA fragmentation and apoptosis,
      but do not affect taxol-induced microtubule bundling or cell cycle growth arrest.
      The delayed onset of taxol-induced DNA fragmentation and apoptosis in 697/BCL-2
      cells without down-regulation of p26BCL-2 levels suggests that an alternative
      mechanism of taxol-mediated apoptosis might be triggered which is unimpeded by
      high p26BCL-2 levels, or taxol-induced prolongation of mitotic arrest may lead to
      the inactivation or inhibition of that mechanism by which p26BCL-2 is able to
      block apoptosis.

PMID- 7526095
TI  - Clouds still gathering over galactosaemia.

PMID- 7526094
TI  - Evidence that ras and myc mediate the synergy between SCF or M-CSF and other
      haemopoietic growth factors.
AB  - We previously reported that M-CSF could mimic the synergistic effect of SCF upon
      myeloid FDC-P1 cells that were first infected with a c-fms retrovirus, which
      encodes the human M-CSFr. We now report that an M-CSFr with a mutation of its
      autophosphorylation site at position 809 was, in response to M-CSF, unable both
      to synergize with IL-3 or GM-CSF and to induce c-myc; whereas a mutant receptor
      with a deletion of its kinase insert was unaffected for these processes. The
      expression of an exogenous c-myc proto-oncogene or a 12H-ras oncogene lowered the
      requirement of FDC-P1 cells for IL-3 or GM-CSF, in a similar manner to M-CSF or
      SCF addition. Furthermore, the expression of either of these genes complemented
      the defective M-CSFr F809. These results strongly support a role for ras and myc
      in the synergistic action of M-CSF and, by implication, of SCF, which implies
      that these signalling intermediates are rate-limiting for the action of IL-3 and
      GM-CSF and possibly other haemopoietic growth factors.

PMID- 7526098
TI  - Randomised trial of thiacetazone and rifampicin-containing regimens for pulmonary
      tuberculosis in HIV-infected Ugandans. The Makerere University-Case Western
      University Research Collaboration.
AB  - Among HIV-positive patients who received treatment for active tuberculosis,
      thiacetazone has been associated with cutaneous hypersensitivity and recurrent
      tuberculosis. No controlled trials have investigated the safety and efficacy of
      thiacetazone-containing regimens compared with alternative regimens among
      patients with HIV. In a randomised clinical trial of 191 HIV-positive patients
      with active pulmonary tuberculosis, we examined the safety and short-term
      efficacy of isoniazid, rifampicin, and pyrazinamide for two months followed by
      isoniazid and rifampicin for seven months (RHZ) compared with streptomycin,
      thiacetazone, and isoniazid for two months followed by thiacetazone and isoniazid
      for ten months (STH). Between May, 1990, and September, 1991, 191 HIV-positive
      adult Ugandan patients with acid-fast bacilli sputum smear-positive pulmonary
      tuberculosis (93% confirmed by culture) received either STH or RHZ. Subjects had
      a standard evaluation that included Mantoux skin test, complete blood count with
      differential white blood cell count, and chest radiography. After starting
      therapy, subjects were followed-up over one year for three outcomes:
      complications of anti-tuberculosis therapy, early sterilisation of cultures, and
      survival. Of 191 eligible subjects, 90 received STH and 101 received RHZ. The
      overall one-year survival was similar for STH and RHZ (65% vs 72%), but when
      controlled for baseline differences in Mantoux reaction size and absolute
      lymphocyte count, the relative risk of death for STH compared with RHZ was 1.57
      (95% CI 1.0-2.48). Overall, 12 adverse drug reactions occurred in the STH arm
      (18.2 reactions per 100 person years [PYO]) compared with one in the RHZ arm (1.6
      reactions per 100 PYO) for a relative risk of 11.7 (95% CI 1.52-90.0). 10
      cutaneous reactions occurred in the STH arm (15.2 events per 100 PYO) compared
      with one event in the RHZ arm (1.6 events per 100 PYO) for a relative risk of 9.7
      (95% CI: 1.24, 75.8). A greater proportion of RHZ patients compared with STH
      patients had sterilised their sputum within two months (74% vs 37%, p < 0.001).
      In developing countries, rifampicin-containing regimens should be given, when
      possible, to HIV-positive patients to reduce drug toxicity and to prolong
      survival.

PMID- 7526096
TI  - Quality of life and survival with continuous hepatic-artery floxuridine infusion
      for colorectal liver metastases.
AB  - Very few patients with liver metastases from colorectal cancer can be cured. We
      have investigated whether a treatment to slow the growth of liver metastases,
      hepatic-artery infusion of floxuridine, improves palliation in this setting. In a
      randomised study of 100 patients, we compared quality of life and survival in
      patients who received hepatic-artery infusion of floxuridine and in those who
      received conventional symptom palliation. 95% of control patient survival time
      was spent with normal quality-of-life scores, which suggests that the aim of
      treatment should be to prolong normal-quality survival rather than merely to
      sustain quality of life. There was a significant prolongation (p = 0.03) in
      overall survival in floxuridine-treated patients compared with controls (median
      405 vs 226 days). There were similar significant prolongations in normal-quality
      (ie, normal symptom scores) survival for physical symptoms (p = 0.04), anxiety (p
      = 0.04), and depression (p = 0.04). This survival benefit was associated with
      significant reductions in metastasis size on computed tomography (p = 0.001) and
      in serum carcinoembryonic antigen concentration (p = 0.006) in floxuridine
      treated patients. There was no evidence of treatment-related hepatotoxicity as
      assessed by serum aspartate aminotransferase and bilirubin measurements. This is
      the first demonstration that survival can be prolonged with normal quality of
      life in patients with colorectal liver metastases. We conclude that hepatic
      artery floxuridine infusion can be recommended for suitable patients.

PMID- 7526099
TI  - Pure red cell aplasia caused by chlormadinone.

PMID- 7526097
TI  - Heparin-induced thrombocytopenia and antithrombotic therapy.

PMID- 7526100
TI  - Expression of inducible nitric oxide synthase in dermal microvasculature in
      psoriasis.

PMID- 7526101
TI  - Raised prostate-specific antigen in adenocarcinoma of lung.

PMID- 7526102
TI  - Inhibition of platelet activity by S-nitrosoglutathione during coronary
      angioplasty.
AB  - Platelet activation is associated with acute vessel occlusion and chronic
      restenosis after percutaneous transluminal coronary angioplasty (PTCA). Organic
      nitrates, which act by releasing the vasodilator and anti-platelet agent nitric
      oxide (NO), have a predominantly vasodilator action and cause hypotension at
      doses required to inhibit platelet activation. S-nitrosoglutathione (GSNO) is an
      NO donor with a preferential action on platelets. We investigated platelet
      activation in patients undergoing PTCA and the effect of GSNO. Blood was sampled
      from the coronary sinus to measure platelet surface expression of P-selectin and
      glycoprotein IIb/IIIa as indices of platelet activation. In 7 control patients,
      PTCA caused a rise in platelet surface expression of P-selectin and glycoprotein
      IIb/IIIa, which was maximal 5 minutes after PTCA, indicating increased platelet
      activation despite treatment with aspirin, glyceryl trinitrate, and heparin. 6
      patients received an intracoronary infusion of GSNO, starting 10 min before PTCA.
      GSNO significantly inhibited the PTCA-induced increase in platelet surface
      expression of P-selectin and glycoprotein IIb/IIIa without altering blood
      pressure. These findings show that platelets are activated following PTCA and
      that GSNO can prevent this activation.

PMID- 7526103
TI  - Colorectal cancer prognosis and expression of exon-v6-containing CD44 proteins.
AB  - CD44 variants containing v6 confer metastatic potential to rat carcinoma cell
      lines. In man, CD44v6 is increasingly expressed during colorectal tumour
      progression. In 68 colorectal carcinoma patients, survival analysis showed that
      CD44v6 expression in the tumours was associated with tumour-related death. In
      patients who had an apparently radical resection of their primary tumour, CD44v6
      expression had prognostic value independent of Dukes' stage. CD44v6 expression
      may reflect propensity for metastasis after apparently curative surgery, making
      adjuvant therapy an option in these patients.

PMID- 7526104
TI  - Filgrastim for lupus neutropenia.

PMID- 7526105
TI  - Inhibitory effect of high-density lipoprotein on platelet function is mediated by
      increase in nitric oxide synthase activity in platelets.
AB  - Although high-density lipoprotein (HDL) has been found to decrease platelet
      function per se, little is known regarding the mechanism of its platelet
      inhibitory effect. In this study, we confirmed the inhibitory effect of HDL on
      platelet aggregation and 14C-serotonin release in thrombin-activated washed human
      platelets. The inhibition of platelet function was associated with an increase in
      nitric oxide synthase activity, measured as the conversion of 3H-L-arginine to 3H
      L-citrulline as well as nitrite release in the platelet supernates. The
      inhibition of platelet function by HDL was reversed by preincubation of washed
      platelets with an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl
      ester (L-NAME), and potentiated by co-incubation with the precursor of nitric
      oxide, L-arginine. These observations suggest that HDL decreases platelet
      function by increasing nitric oxide synthase activity in human platelets.

PMID- 7526106
TI  - Inhibitory effect of galanin on growth hormone release from rat pituitary tumor
      cells (GH1) in culture.
AB  - The growth hormone (GH) releasing effect of GH-releasing hormone (GHRH) and
      galanin, a 29-amino acid peptide widely distributed in mammalian CNS, was
      investigated in cultured rat pituitary tumor cells (GH1) as compared to normal
      rat somatotrophs. GHRH stimulated dose-dependently GH secretion in normal
      somatotrophs but did not affect GH secretion in GH1 cells. Galanin (1-10 microM)
      stimulated GH release in a concentration-dependent manner, but with lower potency
      as compared to GHRH, in normal rat pituitaries but was inhibitory in rat GH1
      cells. The results of this study indicate that while galanin has the ability to
      stimulate GH release from dispersed pituitary cells of normal rats it has potent
      direct inhibitory effects on GH release from tumor rat cells.

PMID- 7526107
TI  - Myocardial magnesium transport: effect of gramicidin S and epinephrine.
AB  - Initial magnesium transport in low magnesium Ringer in the frog myocardium
      consists of at least two systems, a fast system with high capacity with a time
      constant of 30 seconds and a slow transport system that operates with a time
      constant of 165 seconds. Both transport systems appear to be electroneutral and
      can operate either against an electrochemical gradient or with an electrochemical
      gradient. The fast transport system can transport Mg2+ in an outward direction at
      1.84 p mol cm-2 sec-1; the slow system causes Mg2+ to be transported outward at
      0.05 p mol cm-2 sec-1. Gramicidin S (5 microM) decreases the slow outward
      transport system to 0.01 p mol cm-2 sec-1 and at concentrations greater than 1
      microM inhibits not only slow magnesium outflux in low calcium Ringer but also
      inhibits magnesium influx during recovery of Mg2+ in Ringer. Gramicidin S at 5
      microM decreases Mg2+ influx from .04 p mol cm-2 sec-1 to 0.01 p mol cm2 sec-1
      indicating that influx and efflux may take place on the same transport system. In
      the presence of 10 mM Mg2+ Gramicidin S increases magnesium content. Epinephrine
      increases magnesium efflux and overcomes the inhibition of Mg2+ efflux by
      Gramicidin S.

PMID- 7526108
TI  - Histological outcome in patients with chronic hepatitis C given a 60-week
      interferon alfa-2b treatment course.
AB  - Forty patients with chronic hepatitis C virus (HCV) infection were treated with 3
      MU interferon alfa-2b given subcutaneously for 60 weeks. A biochemical response
      with normalization of serum alanine aminotransferase (s-ALT) levels was seen in
      24 patients (60%) at treatment cessation. A sustained response with continuously
      normal s-ALT levels during 24 weeks of follow up was seen in 15 of these 24
      patients (62%), all of whom also became HCV RNA negative in serum. Histological
      changes in the pre- and posttreatment liver biopsies were assessed using a
      numerical scoring system. Biochemical responders had a significant decrease in
      all four scored categories: portal inflammation, piecemeal necrosis, spotty
      necrosis and fibrosis. Non-responders had a significant decrease in piecemeal
      necrosis and spotty necrosis, whereas the scores for portal inflammation and
      fibrosis remained unchanged. There was no significant difference in any of the
      scored categories in the pretreatment biopsy between responders and non
      responders. We conclude that patients suffering from chronic HCV infection who
      responded biochemically and virologically to interferon treatment also improved
      their liver histology. Necroinflammatory activity decreased to some extent in
      biochemical non-responders, possibly giving them some benefit from the treatment,
      but not to the same extent as responders. No specific histological pretreatment
      findings were predictive of biochemical response to interferon treatment.

PMID- 7526110
TI  - A quantitative study of water proton relaxation in packed beds of porous
      particles with varying water content.
AB  - A quantitative analysis of the dependence of water proton relaxation on water
      content in randomly packed beds of Sephadex is undertaken. A combination of
      Osmotic and Capillary theory is used to describe the morphological changes
      occurring in the packed beds as the water content is lowered. At each water
      content the water proton relaxation is calculated using a "proton exchange
      diffusion" model which takes into account fast chemical exchange between water
      and dextran hydroxyl protons and the diffusion of water molecules between the
      water compartments inside and outside the Sephadex beads. The relaxation time
      distribution are shown to provide a sensitive probe of the air-water distribution
      in the bed and of the shrinkage of the Sephadex beads at lower water contents.
      The theoretical models provide an accurate, quantitative description of the
      relaxation behavior except for the largest beads at high water contents when
      there is slow diffusion between the water compartments. In this case, a more
      realistic three-dimensional description of the air-water distribution in a
      randomly packed bed is required.

PMID- 7526111
TI  - Doctors' policy on explaining the implementation of novel experimental treatment
      to cancer patients.
AB  - This article deals with the extent of information which should be provided by
      doctors to cancer patients prior to the implementation of experimental treatment.
      It describes the various factors which affect the extent of information
      disclosed. The study compared oncological patients to vascular patients. From the
      results of the research one can see that doctors in Israel provide extensive
      information about the nature of the medicine as well as side-effects and expected
      benefits prior to the experimental treatment, yet they give less information
      concerning the hazards involved in the treatment. Information offered by doctors
      treating oncological patients is more extensive than that offered by internal
      doctors treating vascular patients.

PMID- 7526109
TI  - HCV-marker-positive autoimmune-type chronic active hepatitis: a possible relation
      between HCV infection and liver autoreaction.
AB  - This study focused on 32 patients who were diagnosed as having autoimmune
      hepatitis based upon clinical and histological factors. Fifteen of these patients
      were positive for HCV-RNA and for one of the HCV-related markers tested,
      including anti-C100, ELISA II, and RIBA 2 (Group 2). The remaining 17 patients
      were negative for all HCV-related markers (Group 1). Clinical factors in the two
      groups, including the frequency of autoantibodies, serum levels of
      aminotransferase and gammaglobulin, HLA phenotypes, and the response to
      corticosteroid treatments, were compared. The titer of serum anti-nuclear
      antibodies and the level of serum aminotransferase at initial diagnosis were
      significantly higher in Group 1 than in Group 2. Furthermore, the genetic
      background of the two groups, as indicated by HLA phenotypes, differed. All cases
      in Group 1 were HLA-DR4-positive, whereas only 60% of those in Group 2 cases had
      HLA-DR4. Also, all cases in Group 1 but only 66.7% of the cases in Group 2 showed
      good clinical responses to corticosteroid treatment. Finally, no cases of HCV
      related-marker-positive autoimmune hepatitis (Group 2) had antibodies for LKM,
      suggesting that these cases were clinically different from type II autoimmune
      hepatitis. These data indicated that immunosuppressive treatment might be the
      preferred initial treatment in patients who either satisfy the criteria for AIH
      or who are sero-positive for an HCV-marker.

PMID- 7526112
TI  - Amyloid precursor protein gene expression in neural cell lines: influence of DNA
      cytosine methylation.
AB  - Transcription of the gene encoding amyloid precursor protein (APP) varies in a
      cell-specific and developmentally regulated manner. The 5' region of this gene
      possesses a high frequency of CpG dinucleotides as well as copies of a GC-rich
      sequence, a potential trans factor binding element. These findings raise the
      possibility that DNA cytosine methylation could participate in the regulation of
      APP gene expression. We examined APP mRNA/18S rRNA ratio in three neural cell
      lines (N18TG2, SN6, SN17) cultured in 5-azacytidine (5-AZA), an inhibitor of
      maintenance methylase which results in loss of cytosine methylation in
      proliferating cells. Culture in 5-AZA globally reduced methylation in genomic DNA
      as assessed by an increase in HpaII restriction sites, reduced cytosine
      methylation in the APP gene as assessed by Southern blotting of HpaII digests,
      and increased APP mRNA steady state abundance in all studied cell lines. Cell
      lines re-acquired APP gene methylation 48 h after removal of 5-AZA from media.
      These results indicate that in vitro alteration of DNA methylation can affect APP
      gene expression, and suggest that the APP gene in neuronal cell lines may be
      rapidly inactivated in vitro, perhaps to neutralize its potential toxicity.

PMID- 7526113
TI  - Down-regulation of glycine receptor channels by protein kinase C in Xenopus
      oocytes injected with synthetic RNA.
AB  - Interaction of protein kinase C (PKC) with glycine receptor channels was examined
      using Xenopus oocytes expressing homomeric alpha 1 glycine channels. 4 beta
      Phorbol 12-myristate 13-acetate (4 beta-PMA), an activator of PKC, reduced the
      response to glycine; this effect was inhibited in the presence of staurosporine,
      a PKC inhibitor. By contrast, 4 alpha-PMA, a poor PKC stimulant, did not affect
      the glycine currents. Thus, the PKC system is involved in negative-regulation of
      the glycine receptor channels. The results obtained from experiments with mutant
      receptors suggest that phosphorylation of the intracellular serine residue at 419
      may relate to modification of the channel function.

PMID- 7526114
TI  - Changes in glutamate receptor and proenkephalin gene expression after kindled
      seizures.
AB  - Changes in gene expression after kindled seizures were examined using
      microdissection of discrete brain areas and Northern and slot blot analyses.
      Experimental animals were kindled with either of two protocols: (1) a paradigm in
      which 50 Hz/10 s stimulus trains were delivered every 30 min through hippocampal
      electrodes (12 stimulations every other day for 4 days) and (2) a traditional
      approach in which 50 Hz/10 s stimulus trains were given to the hippocampus three
      times daily for 16 days. Rats were sacrificed 24 h or 30 days after the last
      kindled seizure. We first examined the possibility that kindling may affect
      transcription of mRNA for neurotransmitter receptors. We found significant
      decreases (22-58%) in AMPA/kainate activated glutamate receptor mRNAs (GluR1, -2,
      -3 mRNAs) in hippocampus, amygdala/entorhinal cortex and in frontoparietal cortex
      24 h but not 30 days after rapidly kindled seizures. However, changes in GABA
      receptor alpha 1, alpha 2, alpha 4 or beta 1 mRNAs were not observed in any brain
      region 30 days after traditional kindling or 24 h after rapidly kindled seizures.
      In addition, we tested whether changes in the expression of proenkephalin could
      be detected after kindling. We found significant increases (1.7-10 fold) in
      proenkephalin mRNA in the frontoparietal cortex, hippocampus and in the
      amygdala/entorhinal cortex 24 h but not 30 days after rapidly kindled seizures.
      Our findings suggest that changes in glutamate receptor and proenkephalin gene
      expression are robust, acute sequelae to kindled seizures and may be involved in
      kindling.

PMID- 7526115
TI  - Mu opioid receptor: expression and vagotomy-induced depletion of the mRNA in
      medullary preganglionic neurons.
AB  - By in situ hybridization with digoxigenin-labeled RNA probes, distinct expression
      of mu opioid receptor mRNA was found in rat medullary preganglionic neurons for
      vagal parasympathetic outflow. Two days or more following unilateral vagotomy,
      the expression was almost completely abolished on the operated side. The results,
      taken together with previous findings indicating proximodistal axonal transport
      of radioligand-labeled opioid receptors, suggest that the medullary preganglionic
      neurons thus identified are the source for mu opioid receptor acting in
      cardiorespiratory and gastrointestinal tissues.

PMID- 7526117
TI  - Microcirculation research, angiogenesis, and microsurgery.
AB  - Angiogenesis, the formation of new blood vessels, is essential to a variety of
      normal and pathologic processes such as wound healing and tumor growth. In
      microsurgery the development of new vessels between the transferred tissue and
      the recipient bed is critical to the final outcome of the reconstruction. Several
      experimental models have been previously developed to study angiogenesis and the
      effect that new substances have on regulating this process, but they lack the
      ability to make quantitative measurements. Therefore, we have developed an animal
      model using the homozygous (hr/hr) hairless mouse ear; by using intravital
      microscopy and computer-assisted analysis, angiogenesis can be quantitatively
      measured. Using this model we showed that basic fibroblast growth factor and
      transforming growth factor beta significantly increased total vessel length by
      32% and 63%, respectively, during 20 days following subcutaneous injection. In
      this paper the importance of angiogenesis research to reconstructive microsurgery
      is presented and discussed.

PMID- 7526116
TI  - Direct visualization and measurements of wound neovascularization: application in
      microsurgery research.
AB  - Neovascularization or angiogenesis is an essential yet poorly understood
      component of the healing process. In wound healing research, there is a lack of
      models enabling quantitative and continuous measurements of wound
      neovascularization. The hairless mouse ear wound model permits quantitative
      measurements of wound epithelialization and neovascularization continuously
      throughout the healing process. On the ears of male homozygous (hr/hr) hairless
      mice, standardized circular full thickness dermal wounds are produced; then,
      using vital microscopy, these two processes are directly viewed and measured at
      day 0 and every third day thereafter until these are complete. This model system
      and its application to clinically relevant situations are reviewed.

PMID- 7526118
TI  - The phage RNA polymerases are related to DNA polymerases and reverse
      transcriptases.
AB  - The single subunit DNA-dependent RNA polymerase (RNAP) that is encoded by
      bacteriophage T7 is the prototype of a class of relatively simple RNAPs that
      includes the RNAPs of the related phages T3 and SP6, as well as the mitochondrial
      RNAPs. The T7 enzyme has been crystallized, and recent genetic and biochemical
      analyses have facilitated an interpretation of this structure. A growing body of
      evidence suggests that the phage-like RNAPs are related to other nucleotide
      polymerases such as DNA polymerases, RNA-dependent RNA polymerases, and reverse
      transcriptases. In this work, we review information concerning the structure and
      function of T7 RNAP, and evidence in support of its assignment to a broader class
      of nucleotide polymerases.

PMID- 7526119
TI  - Expression of meningococcal epitopes in LamB of Escherichia coli and the
      stimulation of serosubtype-specific antibody responses.
AB  - The class 1 outer membrane protein (OMP), a major variable surface antigen of
      Neisseria meningitidis, is a component of novel meningococcal vaccines currently
      in field trials. Serological variants of the protein are also used to serosubtype
      meningococci. Most of the amino acid changes that give rise to antigenic variants
      of the protein occur in two variable regions (VR1 and VR2) that are thought to
      form loops on the cell surface. The polymerase chain reaction (PCR) was used to
      amplify the nucleotide sequences encoding VR1 and VR2 from the chromosomal DNA of
      N. meningitidis strain M1080. These were cloned in frame into the lamB gene of
      the Escherichia coli expression vector pAJC264. Whole-cell enzyme-linked
      immunosorbent assays (ELISAs), using monoclonal antibodies, and SDS-PAGE
      confirmed that, upon induction, strains of E. coli carrying these constructs
      expressed hybrid LamB proteins containing the N. meningitidis surface loops.
      These strains were used to immunize rabbits and the resultant polyclonal antisera
      reacted specifically with the class 1 OMP of reference strain M1080 (P1.7).
      Immunogold labelling of meningococcal cells and whole-cell dot-blot analyses with
      these antisera showed that the variable epitopes were exposed on the cell surface
      and confirmed that this approach could be used to obtain serosubtype-specific
      antisera. The binding profiles of the antisera were determined from their
      reactions with overlapping synthetic peptides and their reactivity compared with
      that of relevant serosubtype-specific monoclonal antibodies. This approach was
      used successfully to raise antisera against two other class 1 OMP VR2s. A fourth
      antiserum raised against a VR2, including the P1.1 epitope, was not subtype
      specific.

PMID- 7526120
TI  - Structural and functional analyses of the FinP antisense RNA regulatory system of
      the F conjugative plasmid.
AB  - The efficiency of conjugation of F-like plasmids is regulated by the FinOP
      fertility inhibition system. The transfer (tra) operon is under the direct
      control of the TraJ transcriptional activator which, in turn, is negatively
      regulated by FinP, an antisense RNA, and FinO, a 22 kDa protein. Recently, FinO
      has been shown to extend the chemical stability of FinP in vivo in the absence of
      traJ mRNA. The in vitro secondary structures of both the FinP and TraJ RNAs were
      determined by the use of single- and double-strand-specific nucleases; both RNAs
      were found to have double stem-loop structures that are complementary to each
      other and, therefore, FinP RNA and TraJ RNA have the potential to form a duplex
      with each other. This was verified by in vitro binding experiments. The reaction
      was shown to be biomolecular with an apparent rate constant (kapp) of 5 x 10(5)M
      1s-1, a value that is similar to those found for other natural antisense RNA
      systems. Preliminary evidence for the in vivo formation of the FinP-TraJ RNA
      duplex was obtained by primer extension of the traJ mRNA; the presence of both
      FinO and FinP was required to cause a dramatic reduction in the steady-state
      level of traJ mRNA, perhaps as a result of RNase III degradation of the resulting
      RNA duplex.

PMID- 7526121
TI  - Immunophilins: structure-function relationship and possible role in microbial
      pathogenicity.
AB  - Immunophilins are housekeeping proteins present in a wide variety of organisms.
      Members of two protein superfamilies, cyclophilins (Cyps) and FK506-binding
      proteins (FKBPs) belong to this class of immunophilins. Despite the fact that the
      amino acid sequences of Cyp and FKBPs do not exhibit noticeable homology to each
      other, proteins of both classes are able to ligate immunosuppressive peptide
      derivatives. Cyps form complexes with the cyclic undercapeptide cyclosporin A and
      FKBPs are able to bind FK506 as well as rapamycin, both of which have a pipecolyl
      bond within their structure. In a ligand-bound form, immunophilins interfere with
      signal transduction in T cells. In addition, immunophilins have peptidyl prolyl
      cis-trans isomerase (PPlase) activity and are able to accelerate the rate of
      conformational events in proline-containing polypeptides. Microorganisms produce
      proteins that exhibit extensive sequence homologies to cyclophilins and FKBPs of
      higher organisms and which have considerable PPlase catalytic activity. While
      cyclophilins seem to be present in most if not all microbial species
      investigated, FKBPs are produced by yeasts as well as by a number of pathogenic
      bacteria, such as Legionella pneumophila, Chlamydia trachomatis and Neisseria
      meningitidis. The Mip protein of L. pneumophila is a virulence factor that plays
      an essential role in the ability of the bacteria to survive and multiply in
      phagocytic cells. Some results are summarized on the structure and putative
      functions of immunophilins and place special emphasis on the contribution of
      these polypeptides to the virulence of pathogenic microorganisms.

PMID- 7526123
TI  - Trends and milestones.

PMID- 7526122
TI  - Structural variation in the O-specific polysaccharides of Klebsiella pneumoniae
      serotype O1 and O8 lipopolysaccharide: evidence for clonal diversity in rfb
      genes.
AB  - The O-polysaccharide fraction of the lipopolysaccharide from Klebsiella
      pneumoniae serotype O8 was found to comprise two galactose-containing
      homopolymers. Structural analysis, using chemical and high-field nuclear magnetic
      resonance (NMR) techniques, established that the K. pneumoniae O8 polysaccharides
      are composed of the linear, disaccharide repeating units [formula: see text] K.
      pneumoniae O8 mutant RFK-1 was isolated by resistance to phage KO1-2; strain RFK
      1 expressed only D-galactan I-OAc. The 1H- and 13C-NMR resonances from this O
      polysaccharide indicate that all of the O-acetyl groups within the K. pneumoniae
      O8 polysaccharide are carried on D-galactan I and O-acetylation occurs only on
      the beta-D-galactofuranose residues; 60% of the available beta-D-galactofuranose
      residues are non-acetylated. The O-acetylation of the remaining residues is
      equally distributed between the O-2 and O-6 positions. The carbohydrate backbone
      structures in the O8 polysaccharide are identical to D-galactan I and II
      expressed by K. pneumoniae O1, accounting for the antigenic cross-reaction
      between strains belonging to serotypes O1 and O8. However, the O1 polysaccharides
      are not acetylated and the O-acetyl groups present in the K. pneumoniae serotype
      O8 polysaccharides provide a structural basis for their recognition as distinct
      serotypes. The rfb (O-polysaccharide biosynthesis) gene cluster of K. pneumoniae
      serotype O1 determines the synthesis of D-galactan I. rfbKpO1-specific gene
      probes were used to examine conservation in the rfb gene clusters of other K.
      pneumoniae serotypes which produce D-galactan I. Six O1 strains were examined and
      all showed hybridization with rfbKpO1 probes under conditions of high stringency.
      Three serotype O2 strains produce D-galactan I and these strains also contained
      DNA sequences recognized by rfbKpO1 probes under high stringency. The physical
      maps of these homologous rfb chromosomal regions showed some polymorphism.
      Surprisingly, the rfbKpO8 region from K. pneumoniae serotype O8 was only
      recognized by rfbKpO1 probes under low-stringency hybridization conditions,
      providing evidence for two substantially different clonal groups of rfb genes
      from K. pneumoniae strains with structurally related O-antigens.

PMID- 7526125
TI  - The influence of endurance training on insulin-like growth factor-1 in older
      individuals.
AB  - Previous cross-sectional studies have suggested that lower levels of insulin-like
      growth factor-1 (IGF-1) in older persons are related in part to diminished
      physical exercise. However, it is unknown whether the introduction of long-term
      exercise in previously inactive older individuals increases IGF-1, and whether
      the response is different between older men and women. Thus, we examined the
      effects of 8 weeks of endurance training on changes in IGF-1, IGF-1 binding
      protein-1 (IGFBP-1), IGFBP-3, and maximal aerobic power (VO2max) in 18 older
      individuals (aged 66.1 +/- 1.4 years, 10 men and eight women). Individuals were
      also characterized for changes in body composition, estimated energy intake, and
      fasting plasma levels of glucose, insulin, and glucagon before and after an
      exercise training program. Endurance training increased VO2max similarly in men
      (14%, P < .01) and women (14%, P < .01), but women showed a smaller increase in
      IGF-1 (8%, NS) than men (19%, P < .01). The correlation between changes in VO2max
      and IGF-1 was significant in men (r = .79, P < .02), but not in women (r = .22,
      NS). Although no mean group change in IGFBP-1 or IGFBP-3 was noted, the
      individual changes between IGF-1 and IGFBP-3 showed a tendency to be related in
      men (r = .48, P = .15), but not in women (-.21, NS). Exercise training decreased
      plasma glucose (P < .05) in men, but not in women.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7526124
TI  - Increased calcium-channel currents of pancreatic beta cells in neonatally
      streptozocin-induced diabetic rats.
AB  - Using a whole-cell patch-clamp technique, voltage-dependent Ca(2+)-channel
      activities were found to be increased in cultured single beta cells isolated from
      neonatally streptozocin-induced diabetic rats (NSZ rats). The current-voltage
      relationship and inactivation time course of Ba2+ currents via L-type Ca2+
      channels were indistinguishable between NSZ and control rats. However, the
      current density observed in NSZ rats was significantly greater than that in
      control rats. Ba2+ currents via T-type Ca2+ channels were also found to be
      enhanced in NSZ beta cells. The insulin-secretory capacity of cultured pancreatic
      islets in response to a depolarizing stimulus (20 mmol/L arginine or 30 mmol/L
      KCl) in the presence of 11.1 mmol/L glucose was augmented in NSZ rats, whereas
      that in response to 11.1 and 16.7 mmol/L glucose alone was significantly reduced.
      It is concluded that the impaired insulinotropic action of glucose in beta cells
      in NSZ rats is not due to reduced activity of voltage-dependent Ca2+ channels.
      The fact that insulin secretion induced by a depolarizing stimulus was enhanced
      in NSZ rats may be related to the augmented activity of the voltage-dependent
      calcium current found in NSZ beta cells.

PMID- 7526126
TI  - Decrease in von Willebrand factor levels after a high-monounsaturated-fat diet in
      non-insulin-dependent diabetic subjects.
AB  - High levels of von Willebrand factor (vWF) have been reported in diabetics with
      vascular complications, suggesting a role for this protein in the development of
      cardiovascular complications in non-insulin-dependent diabetes mellitus (NIDDM).
      Recently, a diet rich in monounsaturated fatty acids (MUFA) has been found to
      improve glycemic control and decrease diurnal blood pressure as compared with a
      high-carbohydrate (H-CHO) diet in NIDDM subjects. To study the impact of MUFA on
      the hemostatic system, we compared the levels of vWF, fibrinogen, fibronectin,
      and alpha 2-macroglobulin before and after 3 weeks on a high-MUFA (H-MUFA) diet
      and on an isocaloric H-CHO diet in 15 NIDDM subjects. In a crossover study, the
      patients were randomly assigned to a H-CHO diet (50% carbohydrate, 30% fat [10%
      MUFA]) or a H-MUFA diet (30% carbohydrate, 50% fat [30% MUFA]). Before and on the
      last day of the two diets, vWF, fibrinogen, fibronectin, and alpha 2
      macroglobulin levels were measured. The H-MUFA diet caused a decrease in vWF from
      1.31 +/- 0.08 to 1.13 +/- 0.08 U/mL (P < .004), whereas an unchanged level was
      observed after a H-CHO diet (1.19 +/- 0.11 v 1.25 +/- 0.11 U/mL, NS). The
      relative changes in vWF during 3 weeks on a H-MUFA and on a H-CHO diet attained 
      12.5% +/- 3.2% versus 5.7% +/- 3.5%, respectively (P < .0001). Furthermore,
      unchanged levels of fibrinogen, fibronectin, and alpha 2-macroglobulin were seen
      after usage of the two diets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526128
TI  - Isolation and identification of eukaryotic receptors promoting bacterial
      internalization.

PMID- 7526127
TI  - Effect of bacterial products on colony-stimulating factor production.

PMID- 7526129
TI  - Methods to visualize actin polymerization associated with bacterial invasion.

PMID- 7526130
TI  - A rapid staining procedure to demonstrate glycocalyx production and bacterial
      biofilms.
AB  - A novel staining procedure to demonstrate glycocalyx production by clinical
      isolates is presented. The short times required, specificity and sensitivity
      suggest that the staining could be applied to routine in vitro diagnostic
      procedures.

PMID- 7526131
TI  - Cat-scratch disease in Italy: a serological approach.
AB  - The results of studies on the serologic responses to Afipia felis and Rochalimaea
      henselae in suspected patients for Cat Scratch Disease (CSD) are illustrated.
      This preliminary study performed using Indirect Immunofluorescence Assay, proved
      negative for A. felis and R. henselae in some patients and positive in others; in
      a few instances the test was positive for both organisms. Additional
      microbiological and serological studies are needed to clarify the exact role of
      these microorganisms in causing CSD.

PMID- 7526132
TI  - An in vitro study to assess the efficacy of antiplaque agents in mouthwash
      formulations.
AB  - A rapid and simple in vitro test to evaluate antiplaque mouthwash formulations
      for their effectiveness in preventing the formation of dental plaque micro
      organisms was investigated. Streptococcus mutans grown in brain heart infusion
      broth containing 5% sucrose was used as the plaque-inducing micro-organism and
      polymethylmethacrylate (Perspex) strips provided the substrate for the deposition
      of plaque. Over a period of 3 days the strips were treated twice daily with
      mouthwash. The Perspex strips were then stained using a plaque disclosing agent,
      and plaque development was measured using a double beam visible
      spectrophotometer. The colour intensity of the strips was recorded by laser
      colour copy to allow visual comparison of results. Two novel antiplaque mouthwash
      formulations, containing 0.05% cetyl pyridinium chloride and 0.05% chlorhexidine
      gluconate respectively were compared with a commercially available product and a
      placebo. The technique provides a simple, reproducible in vitro test which is
      sufficiently sensitive to differentiate between similar formulations.

PMID- 7526133
TI  - Influence of growth rate on the relative activities of free and bound dextranase
      and dextranase inhibitor in continuous cultures of Streptococcus sobrinus.
AB  - The rate of growth of Streptococcus sobrinus was a major factor governing the
      activity of free dextranase and free dextranase inhibitor in continuous culture
      filtrates. Depending on the growth conditions, a variable proportion of
      dextranase and dextranase inhibitor was combined in a tightly bound enzyme
      inhibitor (EI) complex. Dissociation of the EI complexes revealed that the total
      productivity (free + bound) of both the enzyme and the inhibitor increased with
      growth rate, and that the activities of the enzyme and inhibitor released from
      the EI complex greatly exceeded their free activities, when the dilution rate (D)
      was high (D, 0.45 h-1). At low growth rate (D, 0.05 h-1), all the enzyme was
      bound to the inhibitor, and no free dextranase could be determined in culture
      filtrates; by contrast, at high growth rate (D, 0.45 h-1), all the inhibitor was
      bound to dextranase in the active EI complex, leaving active dextranase but no
      free inhibitor.

PMID- 7526134
TI  - Linear and conformation-dependent antigenic sites on the nucleoprotein of rabies
      virus.
AB  - A set of 29 monoclonal antibodies (MAbs) specific for the rabies virus
      nucleoprotein (N protein) was prepared and used to analyze the topography of
      antigenic sites. At least four partially overlapping antigenic sites were
      delineated on the N protein of rabies virus by competitive binding assays.
      Indirect immunofluorescent antibody tests using MAbs with a series of rabies and
      rabies-related viruses showed that epitopes shared by various fixed and street
      strains of rabies virus were mainly localized at antigenic sites II and III,
      while epitopes representing the genus-specific antigen of Lyssavirus were widely
      presented at sites I, III and IV. All but one of seven MAbs specific for
      antigenic sites I, IV and bridge site (I and II) reacted with the antigen that
      had been denatured by sodium dodecyl sulfate or 2-mercaptoethanol, as well as
      with the denatured N protein in Western blotting assays. However, none of the
      MAbs against antigenic sites II and III reacted with the denatured antigen. These
      data indicate that antigenic sites I and IV, and sites II and III on the N
      protein of rabies virus are composed of linear and conformation-dependent
      epitopes, respectively.

PMID- 7526135
TI  - Detection and characterization of antibodies to bacterial heat-shock protein 60
      in sera of patients with primary biliary cirrhosis.
AB  - The enzyme-linked immunosorbent assay (ELISA) with bacterial heat-shock protein
      60 (HSP60) purified from Yersinia enterocolitica (Ye) revealed that the
      antibodies directed against YeHSP60 existed in sera of patients with primary
      biliary cirrhosis (PBC). To characterize the epitope specificity of the
      antibodies in patients, the epitope mapping of HSP60 by means of the antibodies
      was performed. The results have suggested that the epitope recognized with anti
      HSP60 antibodies in PBC relates to the amino acid sequence of YeHSP60 molecule as
      follows: DLGQAKRVVINKDTTIIIDGVGDEAAIQGRLAQIRQQIEEATSDYDKEK.

PMID- 7526137
TI  - Selective non-treatment of newborn infants.

PMID- 7526136
TI  - Mechanisms involved in living systems organisation, especially the programming
      necessary to enable the construction of individuals in three dimensions.
AB  - The complexity of the organization of living systems escalates by orders of
      magnitude in the development, from single precursor cells, not only of the three
      dimensional structures characterizing each species but also in the variations
      necessary to accommodate the 1 million or more separate and identifiable species
      on this planet. Although the genetic information controlling such information is
      currently considered to reside in cellular DNA, it is also held that such
      information is restricted to a linear form encoding specifically for protein.
      However, this not only fails to explain the co-ordination of the vast number of
      processes occurring in simple, single cell, organisms, but also the integration
      of cellular activities to serve the interest of the total system. In particular
      how can a homeobox containing only genes encoding specifically for proteins
      organize and implement the mechanisms necessary for three-dimensional
      development? This, and the organization and implementation of the massive amount
      of information necessary to execute the construction of such a wide range of
      species, each in its own unique and exquisite detail, calls for internal
      programming of a highly complex and sophisticated nature. It is proposed here
      that such a central computer-analog program does exist, housed in the molecular
      electronic structure of cellular nucleic acid, primarily in DNA: its possible
      nature is discussed. Since precursor cells contain only of the order of 10(-10) g
      of DNA, this proposal involves an increase in information storage efficiency
      comparable with that already achieved by silicon microprocessors over mechanical
      calculators.

PMID- 7526139
TI  - Wanted: guidelines for "Palliative" anti-cancer drug use.

PMID- 7526138
TI  - Wanted: guidelines for "palliative" anti-cancer drug use.

PMID- 7526141
TI  - Euthanasia: attitudes and practices of medical practitioners.

PMID- 7526140
TI  - Wanted: guidelines for "palliative" anti-cancer drug use.

PMID- 7526142
TI  - Euthanasia: attitudes and practices of medical practitioners.

PMID- 7526143
TI  - High-dose epirubicin and r-met-hu G-CSF (filgrastim) in the treatment of patients
      with advanced breast cancer: A Hellenic Cooperative Oncology Group study.
AB  - The delivery of high-dose epirubicin in patients with advanced breast cancer
      usually entails serious myelotoxicity and frequent treatment delays. Concurrent
      administration of G-CSF probably allows the administration of epirubicin on
      schedule with minimal morbidity. From August 1990 to February 1992, 42 women with
      advanced breast cancer were treated with six cycles of epirubicin 110 mg/m2 every
      4 weeks. Filgrastim 5 micrograms/kg per day for 14 days was administered
      subcutaneously starting 24 hours after chemotherapy. All patients had multiple
      metastatic sites, and 39 had visceral metastases. All cases were evaluable for
      response, toxicity, and survival. Treatment was delayed in only two cases. The
      actually administered average dose per unit time per patient amounted to 99.6% of
      the dose prescribed by the protocol. Two (4.5%; 95% confidence interval [C.I.] 0
      16%) patients demonstrated a complete response and 14 (33%; 95% C.I. 19-49%) a
      partial response. Median time to progression was 31 weeks and median survival was
      60 weeks. Severe granulocytopenia was seen in six patients; stomatitis and
      diarrhea in one patient each. Myoskeletal pain was noticed in 23 (55%) patients,
      while cardiac problems were reported in 3 cases. The present study shows that the
      prophylactic use of r-met-hu G-CSF allows the administration of high-dose
      epirubicin every 4 weeks with minimal morbidity and an improved quality of life.

PMID- 7526144
TI  - [Rational therapy with G-CSF and GM-CSF].

PMID- 7526146
TI  - PCP/NMDA receptor-channel complex and brain development.
AB  - Phencyclidine (PCP) acts on a variety of neurotransmitter systems--cholinergic,
      catechoaminergic, indoleaminergic, and peptidergic--but the dose at which it
      produces its psychotomimetic effects is lower than the concentration at which it
      affects these systems. At low doses, PCP interacts primarily with a binding site
      located within the ionophore associated with the NMDA receptor complex--binding
      to this site has been used as a biochemical marker for NMDA channel activity.
      PCP/NMDA receptor-channel complex has been shown to play an important role in
      brain development but little is known of the neurochemical effects following
      postnatal administration of NMDA antagonists in rats. In the present study, rats
      were treated with PCP from Day 5 until Day 15 after birth and binding to the PCP
      receptor was measured on postnatal Day 21 using [3H]MK-801; MK-801 is a more
      potent and specific ligand at the PCP receptor than PCP itself. Postnatal PCP
      administration produced specific alterations in PCP receptor binding in 21-day
      old rat forebrain. There was a reduction in the high affinity component of [3H]MK
      801 binding under baseline binding conditions. In the presence of both L
      glutamate and glycine, [3H]MK-801 binding in PCP-treated rats increased
      significantly compared to baseline but did not differ from saline-treated
      controls. These findings suggest that chronic PCP administration in developing
      rats alter NMDA channel functioning which could have long-term neurobehavioral
      consequences.

PMID- 7526145
TI  - Modulation of the PCP/NMDA receptor complex and sigma binding sites by
      psychostimulants.
AB  - The present study was undertaken to determine the role and modulation of the
      PCP/NMDA receptor complex and sigma binding sites in the central nervous system
      of animals treated with psychostimulant agents. Repeated exposure of mice to
      cocaine (45 mg/kg/day; for 7 days) was associated with a progressive increase in
      convulsive response and lethality rate. The sensitization to the toxic effects of
      cocaine in mice was completely abolished by pretreatment with either the
      noncompetitive NMDA receptor antagonist MK-801 (0.35 mg/kg/day), or the nitric
      oxide synthase inhibitor Ng-nitro-L-arginine methyl ester (100 mg/kg/day).
      Parallel in vitro receptor binding assays indicated first, upregulation of
      cortical NMDA receptors labeled with [3H]CGP 39653, and second, glutamate
      dependent sensitization of [3H]MK-801 binding to the PCP site in cortical
      membranes of the mice treated for 7 days with cocaine. Repeated exposure of rats
      to methamphetamine (4.0 mg/kg/day; for 10 days) resulted in a significant
      upregulation of the sigma-1 binding site labeled with (+)[3H]pentazocine in the
      frontal cortex and substantia nigra. The cocaine-related studies suggest that the
      PCP/NMDA receptor complex is involved in the development of sensitization to the
      neurotoxic effects of the drug, such as "pharmacological kindling". The
      methamphetamine-related studies insinuate a potential role of sigma-1 binding
      sites in psychostimulant-induced behavioral disorders.

PMID- 7526148
TI  - Gold sodium thiomalate down-regulates intercellular adhesion molecule-1 and
      vascular cell adhesion molecule-1 expression on vascular endothelial cells.
AB  - We examined whether antirheumatic drugs alter cytokine- or lipopolysaccharide
      induced expression of adhesion molecules on vascular endothelial cells. Human
      umbilical cord vein endothelial cells were co-cultured with various antirheumatic
      drugs in the presence of inflammatory cytokines, and adhesion molecule expression
      was measured by cell enzyme-linked immunosorbent assay and Northern blot
      analysis. Among these antirheumatic drugs, gold sodium thiomalate significantly
      inhibited intercellular adhesion molecule-1 and vascular cell adhesion molecule-1
      expression on vascular endothelial cells and suppressed cellular binding between
      human monocytic cell lines, including U937 and HL-60 cells, and interleukin-1
      beta-stimulated vascular endothelial cells. It is speculated that down-regulation
      of adhesion molecules might be one of the novel mechanisms of action of gold
      sodium thiomalate.

PMID- 7526147
TI  - Sexually dimorphic effects of perinatal alcohol exposure on social interactions
      and amygdala DNA and DOPAC concentrations.
AB  - The hypotheses that exposure of rats to alcohol during a period roughly
      equivalent to the human third trimester induces changes in social interactions
      and neurotransmitter and DNA concentrations in the amygdala region were examined.
      The alcohol exposure was accomplished via an artificial rearing procedure. There
      were two alcohol-exposed groups (3 and 5 g/kg/day of ethanol) and two control
      groups (one artificially reared but not exposed to alcohol and one reared
      normally by dams) in all studies. Active social interactions were reduced in the
      male 5 g/kg/day group and increased in both female alcohol-exposed groups
      compared to their respective control groups. Exposure to 5 g/kg/day of alcohol
      reduced the DNA concentration in the amygdala region of male rats compared to
      either control group; there were no effects in females. Because some systems have
      been shown to exhibit alcohol-induced changes only under stressed conditions,
      noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5
      hydroxyindoleacetic acid (5-HIAA) concentrations were measured in the amygdala
      region under both nonstressed and stressed conditions. The stress-induced
      increase in DOPAC concentrations was enhanced in the female high dose group
      compared to either control group; there were no effects in males. In summary,
      alcohol exposure during the early postnatal period altered social interactions
      and DOPAC and DNA concentrations in the amygdala region in a sexually dimorphic
      manner.

PMID- 7526149
TI  - Physicochemical and immunocytochemical analysis of the aryl hydrocarbon receptor
      nuclear translocator: characterization of two monoclonal antibodies to the aryl
      hydrocarbon receptor nuclear translocator.
AB  - The aryl hydrocarbon receptor nuclear translocator (Arnt) is a basic helix-loop
      helix transcription factor that heterodimerizes with the aryl hydrocarbon
      receptor to mediate signal transduction pathways inducible by 2,3,7,8
      tetrachlorodibenzo-p-dioxin and other planar aromatic hydrocarbons. Monoclonal
      antibodies (MAbs) have been raised against a carboxyl-terminal 19-amino acid
      peptide hapten (MAb 2B10) and against a carboxyl-terminal 378-amino acid
      polypeptide-staphylococcal Protein A fusion protein (MAb 4G9) of Arnt and their
      characterization is described. Western blot experiments show that both MAbs
      specifically cross-react with an approximately 85-kDa band in cytosol prepared
      from COS-7 cells transfected with the full length human Arnt cDNA pBMSNeo-D24-1
      and in Hepa 1c1c7 cytosol but not in Arnt-deficient Hepa 1-C4 mutant cytosol.
      Velocity sedimentation of Hepa 1c1c7 cytosol on sucrose gradients and Superose 6
      gel permeation chromatography were used to estimate the sedimentation
      coefficient. Stokes radius, and relative molecular mass of Arnt as approximately
      3.6-4.1 S, 6.8 nm, and 101-115 kDa, respectively. These results indicate that
      Arnt probably exists in monomeric form in Hepa 1c1c7 cytosolic extracts. Laser
      scanning confocal microscopy and indirect immunofluorescence microscopy revealed
      Arnt to be distributed throughout the non-nucleolar portion of the nucleus of
      Hepa 1c1c7, VT(2) (Hepa 1-C4T mutant cell line deficient in Arnt function and
      stably transfected with pBMSNeo D24-1, expressing the full length human Arnt
      cDNA), and HeLa cells. The establishment of the nuclear localization of Arnt in
      human and murine cell lines shown here indicates that its nuclear localization
      may be conserved across species. Immunofluorescence analysis of Arnt in three
      cell lines using two MAbs (to distinct epitopes) provides evidence that suggests
      that the aryl hydrocarbon receptor heterodimerizes with Arnt in the nucleus.

PMID- 7526150
TI  - Time course of 72-kilodalton heat shock protein induction and appearance of
      trifluoroacetyl adducts in livers of halothane-exposed rats.
AB  - Previous studies have shown that exposure of phenobarbital-pretreated rats to
      halothane in 10% O2 causes centrilobular necrosis, induces expression of the 72
      kDa heat shock protein (HSP72), and produces several trifluoroacetylated adducts.
      In the present study the time course of development of the centrilobular lesion,
      as measured by histochemistry, was compared with the time course of appearance of
      both trifluoroacetylated adducts and HSP72, as measured by Western blotting. One
      group of 20 rats was pretreated with phenobarbital for 5 days, whereas a second
      group of two rats was left as untreated controls. Ten phenobarbital-pretreated
      rats were exposed for 2 hr to 1% halothane in 10% O2 and 10 were exposed to 1%
      halothane in 20% O2. At either 2, 4, 6, or 24 hr after exposure, livers were
      excised and frozen without fixation. Thin sections stained with hematoxylin and
      eosin demonstrated that centrilobular lesions occurred at 6 hr and became
      extensive at 24 hr in rats pretreated with phenobarbital and exposed to 1%
      halothane in 10% O2. The time course of appearance of both trifluoroacetylated
      adducts and HSP72 was determined by Western blotting. Trifluoroacetylated adducts
      appeared in all rats exposed to halothane by 2 hr, lasted until 6 hr, and then
      diminished by 24 hr. In contrast, HSP72 was induced only in the rats pretreated
      with phenobarbital and exposed to 1% halothane in 10% O2. HSP72 appeared in both
      the nuclear and supernatant fractions at 6 hr after exposure and was intense 24
      hr after exposure.

PMID- 7526151
TI  - AP-1, ETS, and transcriptional silencers regulate retinoic acid-dependent
      induction of keratin 18 in embryonic cells.
AB  - The differentiation of both embryonal carcinoma (EC) and embryonic stem (ES)
      cells can be triggered in culture by exposure to retinoic acid and results in the
      transcriptional induction of both the endogenous mouse keratin 18 (mK18)
      intermediate filament gene and an experimentally introduced human keratin 18
      (K18) gene as well as a variety of other markers characteristic of extraembryonic
      endoderm. The induction of K18 in EC cells is limited, in part, by low levels of
      ETS and AP-1 transcription factor activities which bind to sites within a complex
      enhancer element located within the first intron of K18. RNA levels of ETS-2, c
      Jun, and JunB increase upon the differentiation of ES cells and correlate with
      increased expression of K18. Occupancy of the ETS site, detected by in vivo
      footprinting methods, correlates with K18 induction in ES cells. In somatic
      cells, the ETS and AP-1 elements mediate induction by a variety of oncogenes
      associated with the ras signal transduction pathway. In EC cells, in addition to
      the induction by these limiting transcription factors, relief from negative
      regulation is mediated by three silencer elements located within the first intron
      of the K18 gene. These silencer elements function in F9 EC cells but not their
      differentiated derivatives, and their activity is correlated with proteins in F9
      EC nuclei which bind to the silencers and are reduced in the nuclei of
      differentiated F9 cells. The induction of K18, associated with the
      differentiation of EC cells to extraembryonic endoderm, is due to a combination
      of relief from negative regulation and activation by members of the ETS and AP-1
      transcription factor families.

PMID- 7526153
TI  - CD45 tyrosine phosphatase activity and membrane anchoring are required for T-cell
      antigen receptor signaling.
AB  - T cells that lack the CD45 transmembrane tyrosine phosphatase have a variety of T
      cell receptor (TCR) signaling defects that are corrected by reexpression of wild
      type CD45 or its intracytoplasmic domains. In this study, a chimeric molecule
      containing the myristylation sequence of Src and the intracellular portion of
      CD45, previously shown to restore function in CD45- T cells, was mutagenized to
      determine if membrane-associated CD45 tyrosine phosphatase activity is required
      to restore TCR-mediated signaling in CD45- T cells. Abolition of enzymatic
      activity by substitution of a serine for a critical cysteine in the first
      catalytic domain resulted in failure of this molecule to restore TCR signaling.
      Another mutation, in which a single amino acid substitution destroyed the
      myristylation site, resulted in failure of the chimeric molecule to partition to
      the plasma membrane. Although expressed at high levels and enzymatically active,
      this form of intracellular CD45 also failed to restore normal signaling in CD45-
      T cells. These findings strongly suggest that CD45's function in TCR signaling
      requires its proximity to membrane-associated tyrosine phosphatase substrates.

PMID- 7526152
TI  - Interferons block protein kinase C-dependent but not-independent activation of
      Raf-1 and mitogen-activated protein kinases and mitogenesis in NIH 3T3 cells.
AB  - Interferons (IFNs) exert antiproliferative effects on many types of cells. The
      underlying molecular mechanism, however, is unclear. One possibility is that IFNs
      block growth factor-induced mitogenic signaling, which involves activation of
      Ras/Raf-1/MEK/mitogen-activated protein kinase. We have tested this hypothesis by
      using HER14 cells (NIH 3T3 cell expressing both platelet-derived growth factor
      [PDGF] and epidermal growth factor [EGF] receptors) as a model system. Our
      studies showed that IFNs (alpha/beta and gamma) blocked PDGF-and phorbol ester-
      but not EGF-stimulated DNA synthesis and cell proliferation. While the ligand
      stimulated receptor tyrosine phosphorylation and interaction with downstream
      signaling molecules, such as GRB2, were not affected, IFNs specifically blocked
      PDGF- and phorbol ester- but not EGF-stimulated activation of Raf-1, mitogen
      activated protein kinases, and tyrosine phosphorylation of an unidentified 34-kDa
      protein. This inhibition could be detected as early as 5 min after IFN treatments
      and was insensitive to cycloheximide, indicating that de novo protein synthesis
      is not required. The IFN-induced inhibition acted upstream of Raf-1 kinase and
      downstream of diacyl glycerol/phorbol ester, suggesting that protein kinase C
      (PKC) is the potential primary target. Consistently, downregulation of PKC by
      chronic phorbol myristate acetate treatment or inhibition of PKC by H7 and
      staurosporine blocked PDGF- and phorbol myristate acetate- but not EGF-induced
      signaling and DNA synthesis. Moreover, incubating cells with antisense
      oligodeoxyribonucleotides of PKC delta eliminated production of PKC delta protein
      and specifically blocked PDGF- but not EGF-stimulated mitogenesis in these cells.
      Thus, these studies have elucidated a major difference in the early events of EGF
      and PDGF-stimulated signal transduction and, more importantly, revealed a novel
      mechanism by which IFNs may execute their antiproliferative function.

PMID- 7526155
TI  - MID1, a novel Saccharomyces cerevisiae gene encoding a plasma membrane protein,
      is required for Ca2+ influx and mating.
AB  - By establishing a unique screening method, we have isolated yeast mutants that
      die only after differentiating into cells with a mating projection, and some of
      them are also defective in Ca2+ signaling. The mutants were classified into five
      complementation groups, one of which we studied extensively. This mutation
      defines a new gene, designated MID1, which encodes an N-glycosylated, integral
      plasma membrane protein with 548 amino acid residues. The mid1-1 mutant has low
      Ca2+ uptake activity, loses viability after receiving mating pheromones, and
      escapes death when incubated with high concentrations of CaCl2. The MID1 gene is
      nonessential for vegetative growth. The efficiency of mating between MATa mid1-1
      and MAT alpha mid1-1 cells is low. These results demonstrate that MID1 is
      required for Ca2+ influx and mating.

PMID- 7526154
TI  - Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I
      interferon receptor by p135tyk2 tyrosine kinase.
AB  - Binding of type I interferons (IFNs) to their receptors induces rapid tyrosine
      phosphorylation of multiple proteins, including the alpha and beta subunits of
      the receptor, the polypeptides that form the transcriptional activator ISGF3
      alpha (Stat113, Stat84, and Stat91), and the p135tyk2 and Jak-1 tyrosine kinases.
      In this report, we demonstrate that the alpha subunit of the type I IFN receptor
      (IFN-R) corresponds to the product of a previously cloned receptor subunit cDNA
      and, further, that the p135tyk2 tyrosine kinase directly binds and tyrosine
      phosphorylates this receptor subunit. Glutathione S-transferase (GST) fusion
      proteins encoding the different regions of the cytoplasmic domain of the alpha
      subunit can bind the p135tyk2 contained in human cell lysates. The association
      between the alpha subunit and Tyk2 was demonstrated by immunoblotting with anti
      Tyk2 and antiphosphotyrosine antibodies and by using an in vitro kinase assay.
      Analogous experiments were then performed with recombinant baculoviruses encoding
      constitutively active Jak family tyrosine kinases. In this case, p135tyk2, but
      not Jak-1 or Jak-2 protein, binds to the GST-IFN-R proteins, suggesting that the
      interaction between these two proteins is both direct and specific. We also
      demonstrate that Tyk2, from extracts of either IFN alpha-treated human cells or
      insect cells infected with the recombinant baculoviruses, can catalyze in vitro
      phosphorylation of GST-IFN-R protein in a specific manner. Deletion mutants of
      the GST-IFN-R protein were used to localize both the binding and tyrosine
      phosphorylation site(s) to a 46-amino-acid juxtamembrane region of the alpha
      subunit, which shows sequence homology to functionally similar regions of other
      cytokine receptor proteins. These data support the hypothesis that the Tyk2
      protein functions as part of a receptor complex to initiate intracellular
      signaling in response to type I IFNs.

PMID- 7526157
TI  - Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal
      pattern.
AB  - Ubiquitin cross-reactive protein (UCRP), a 15-kDa interferon-induced protein, is
      a sequence homolog of ubiquitin that is covalently ligated to intracellular
      proteins in a parallel enzymatic reaction and is found at low levels within
      cultured cell lines and human tissues not exposed to interferon. Ubiquitin and
      UCRP ligation reactions apparently target distinct subsets of intracellular
      proteins, as judged from differences in the distributions of the respective
      adducts revealed on immunoblots. In this study, successive passages of the human
      lung carcinoma line A549 in the presence of neutralizing antibodies against alpha
      and beta interferons had no effect on the levels of either free or conjugated
      UCRP, indicating that these UCRP pools are constitutively present within
      uninduced cells and are thus not a consequence of autoinduction by low levels of
      secreted alpha/beta interferon. In an effort to identify potential targets for
      UCRP conjugation, the immunocytochemical distribution of UCRP was examined by
      using affinity-purified polyclonal antibodies against recombinant polypeptide.
      UCRP distributes in a punctate cytoskeletal pattern that is resistant to
      extraction by nonionic detergents (e.g., Triton X-100) in both uninduced and
      interferon-treated A549 cells. The cytoskeletal pattern colocalizes with the
      intermediate filament network of epithelial and mesothelial cell lines.
      Immunoblots of parallel Triton X-100-insoluble cell extracts suggest that the
      cytoskeletal association largely results from the noncovalent association of UCRP
      conjugates with the intermediate filaments rather than direct ligation of the
      polypeptide to structural components of the filaments. A significant increase in
      the sequestration of UCRP adducts on intermediate filaments accompanies
      interferon induction. These results suggest that UCRP may serve as a trans-acting
      binding factor directing the association of ligated target proteins to
      intermediate filaments.

PMID- 7526156
TI  - Identification of a new catenin: the tyrosine kinase substrate p120cas associates
      with E-cadherin complexes.
AB  - p120cas is a tyrosine kinase substrate implicated in ligand-induced receptor
      signaling through the epidermal growth factor, platelet-derived growth factor,
      and colony-stimulating factor receptors and in cell transformation by Src. Here
      we report that p120 associates with a complex containing E-cadherin, alpha
      catenin, beta-catenin, and plakoglobin. Furthermore, p120 precisely colocalizes
      with E-cadherin and catenins in vivo in both normal and Src-transformed MDCK
      cells. Unlike beta-catenin and plakoglobin, p120 has at least four isoforms which
      are differentially expressed in a variety of cell types, suggesting novel means
      of modulating cadherin activities in cells. In Src-transformed MDCK cells, p120,
      beta-catenin, and plakoglobin were heavily phosphorylated on tyrosine, but the
      physical associations between these proteins were not disrupted. Association of
      p120 with the cadherin machinery indicates that both Src and receptor tyrosine
      kinases cross talk with proteins important for cadherin-mediated cell adhesion.
      These results also strongly suggest a role for p120 in cell adhesion.

PMID- 7526159
TI  - A comparison of human and murine monoclonal IgGs specific for the P1.7 PorA
      protein of Neisseria meningitidis.
AB  - Monoclonal human IgG SS269 reacts with Neisseria meningitidis expressing the P1.7
      PorA protein and with linear peptides containing NGGAS, which accounts for the
      P1.7 specificity. Murine monoclonal antibody to P1.7 reacts with peptides
      containing the overlapping epitope, ASGQ. The human and murine antibodies have
      similar affinities. The low avidity human antibody is very inefficient at
      stimulating complement-mediated bactericidal killing while the high avidity
      murine antibody efficiently kills bacteria. However, efficient opsonophagocytosis
      was mediated even at low concentrations of the human antibody and in the absence
      of complement, suggesting that low avidity antibodies might be protective against
      disease.

PMID- 7526160
TI  - Late-onset ataxia telangiectasia in two brothers presenting with juvenile resting
      tremor.
AB  - Two young adult brothers presented with a 5- to 6-Hz resting tremor of the upper
      limbs. Although ataxia was not unequivocally present and ocular telangiectasia
      was minimal, typical rearrangements of chromosomes 7 and 14, and increased alpha
      feto-protein levels indicated the presence of ataxia telangiectasia (AT). Resting
      tremor as a predominating symptom in AT is uncommon and to our knowledge has not
      been described previously.

PMID- 7526161
TI  - Mechanisms of autoantibody production and their role in disease.

PMID- 7526158
TI  - Tec kinase associates with c-kit and is tyrosine phosphorylated and activated
      following stem cell factor binding.
AB  - Stem cell factor (SCF) plays a crucial role in hematopoiesis through its
      interaction with the receptor tyrosine kinase c-kit. However, the signaling
      events that are activated by this interaction and involved in the control of
      growth or differentiation are not completely understood. We demonstrate here that
      Tec, a cytoplasmic, src-related kinase, physically associates with c-kit through
      a region that contains a proline-rich motif, amino terminal of the SH3 domain.
      Following SCF binding, Tec is tyrosine phosphorylated and its in vitro kinase
      activity is increased. Tyrosine phosphorylation of Tec is not detected in the
      response to other cytokines controlling hematopoiesis, including colony
      stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor
      (GM-CSF), and interleukin-3 (IL-3). Conversely, the cytoplasmic kinase JAK2 is
      activated by IL-3 but not by SCF stimulation. The activation of distinct
      cytoplasmic kinases may account for the synergy seen in the actions of SCF and IL
      3 on hematopoietic stem cells.

PMID- 7526162
TI  - Spontaneous mutation at codon 61 of the Ha-ras gene in the nascent liver of
      B6C3F1, C3H/He and C57BL/6 mice.
AB  - DNA was isolated from the liver of young B6C3F1, C3H/He and C57BL/6 mice, 6-9
      weeks old. A portion of exon 2 of Ha-ras was amplified by PCR allele-specific
      amplification. The PCR product was identified by (a) size, (b) presence of a
      diagnostic restriction site, and (c) direct sequencing. Our results indicate that
      nascent mouse liver bears a subpopulation of cells which contain a mutation in
      codon 61 of Ha-ras, specifically an A to G transition at position 2. Therefore,
      the detection of this mutation in chemically induced mouse liver tumors does not
      demonstrate that the chemical in question acts as a mutagen. It might act by a
      nongenotoxic mechanism, i.e., by facilitating a clonal expression of cells
      bearing this spontaneous mutation.

PMID- 7526163
TI  - Ruv and recG genes and the induced precise excision of Tn10 in Escherichia coli.
AB  - Induction of precise excision of Tn10 by UV or mitomycin C (MMC) is dependent on
      the expression of the SOS system. Ruv mutants of Escherichia coli, which are
      defective in DNA repair and recombination, showed diminished frequencies of both
      spontaneous and UV- or MMC-induced excision of Tn10 inserted in gal. RecG
      mutants, which are also defective in DNA repair and recombination, showed
      decreased induction of Tn10 excision with MMC, but not after UV treatment. A recG
      ruv double mutant showed a greater decrease in induction of excision with MMC
      than either single mutant. One can speculate that the Ruv proteins, which are
      known to be involved in the resolution of Holliday junctions, might also be
      involved in the resolution of putative intermediates generated during the precise
      excision of Tn10. RecG protein, whose function partially overlaps those of Ruv
      proteins, might also have some role in this process.

PMID- 7526164
TI  - A new shuttle vector system for the identification of spontaneous and radiation
      induced mutations in the fission yeast Schizosaccharomyces pombe.
AB  - A shuttle vector, pCRR1, has been constructed for the detection of spontaneous
      and radiation-induced mutations in the fission yeast Schizosaccharomyces pombe.
      This vector contains an Escherichia coli supF suppressor tRNA gene as the target
      for mutagenesis and bacterial pMB1 and yeast ars1 replication origins, which can
      be used to propagate the plasmid in bacterial and fission yeast cells,
      respectively. supF mutations can be detected after plasmid transformation into S.
      pombe and recovery in a bacterial indicator system, KS40/pKY241, by selecting for
      nalidixic acid resistance and/or by screening for lacZ- cells. We found that UV
      light or gamma-rays induced mutations in a dose-dependent manner in this system.
      Treatment of ultraviolet light (UV)-irradiated DNA with E. coli photolyase, which
      monomerizes cyclobutane pyrimidine dimers, before introduction into S. pombe
      reduced mutation frequencies to nearly background levels, indicating that this
      type of lesion is the major source of mutations. Comparison of spontaneous and UV
      induced mutation frequencies in rad+, rad8-190 and rad13-A cells revealed no
      significant difference in background levels or induced levels after exposure to
      100 J/m2 of UV. However, when plasmid DNA was UV-irradiated with 500 J/m2, the
      rad8-190 cells generated only 38% as many induced supF mutations as the rad+
      strain, whereas the rad13-A cells produced more than a 6-fold increase in
      mutability relative to the level observed for the wild-type strain. These
      mutability patterns are consistent with previous studies that characterized rad8
      190 cells as hypomutable and rad13-A cells as hypermutable by UV light at
      chromosomal loci. Thus, this shuttle vector system provides a useful and
      sensitive tool to assess mutability in S. pombe.

PMID- 7526166
TI  - Cytogenetic effects of deltamethrin on rat bone marrow.
AB  - Deltamethrin, a synthetic pyrethroid insecticide, was administered to adult
      female albino rats as a single i.p., s.c., or oral dose of 5.6, 8.4, or 11.2
      mg/kg b.w. or repeated i.p. doses of 2.24 mg/kg b.w. for five consecutive days
      (cumulative dose 11.2 mg/kg b.w.). This treatment inhibited the mitotic index in
      a dose-dependent manner and increased the frequency of chromosome aberrations in
      the bone marrow at 24 h post exposure. The parenterally (i.p. and s.c.)
      administered deltamethrin appeared more effective than the oral gavage for
      eliciting its cytotoxicity and genetic toxicity potential. The frequency of
      micronucleated erythrocytes in the bone marrow was also increased at 30 h
      following a single i.p. dose of 5.6, 8.4, or 11.2 mg/kg b.w. The most prevalent
      abnormality observed in this study was endomitotic reduplication of chromosomes
      which, along with mitotic inhibition and micronucleus induction, indicated
      microtubular/mitotic spindle poisoning by deltamethrin. The increased frequency
      of chromosome aberrations and micronucleated erythrocytes also suggests a
      clastogenic potential of deltamethrin. These observations indicate the in vivo
      susceptibility of mammals to the genetic toxicity potential of deltamethrin.

PMID- 7526165
TI  - Chromosome terminal deletion formation in Chinese hamster ovary cells.
AB  - To investigate the fate of unrejoined DNA double-strand breaks, the frequency of
      60Co gamma-ray- and restriction-enzyme-induced terminal chromosome deletions, a
      marker of unrejoined breaks, was determined in CHO-K1 and in xrs-5 cells. The xrs
      5 cell is a DNA double-strand break repair-deficient derivative of CHO-K1.
      Terminal deletion frequency was small in both CHO-K1 and xrs-5 cells when cells
      were irradiated or treated with restriction enzyme while in the G1 phase of the
      cell cycle. In contrast, previous studies have shown that treatment of cells in
      G2 leads to large deletion frequencies, especially in xrs-5 cells. Cell cycle
      analyses show large G2 blocks in irradiated xrs-5 cells with only partial
      recovery over a 24-96-h period. These results suggest that most CHO cells with
      unrejoined breaks are blocked in G2 and, therefore, do not contribute to
      chromosome mutation frequencies. The small frequencies of terminal deletions that
      are found in these cells may reflect either an inefficiency in the G2 checkpoint
      mechanism or, perhaps, a modification of broken ends that allows passage through
      G2.

PMID- 7526167
TI  - Analysis of in vivo mutation in exon 8 of the rat hprt gene.
AB  - We have analyzed mutations in exon 8 of the hypoxanthine-guanine
      phosphoribosyltransferase (hprt) gene in T-lymphocytes from the spleens of
      ethylnitrosourea-treated female rats. Presumptive hprt- mutants were isolated by
      clonal growth in the presence of 6-thioguanine. DNA from 6-thioguanine-resistant
      colonies was amplified by the polymerase chain reaction using intronic primers
      flanking hprt exon 8. The identification of mutant sequences and the separation
      of mutant DNA from contaminating wild-type DNA was accomplished by denaturing
      gradient gel electrophoresis. Of 118 clones analyzed, 19 contained mutations and
      DNA sequence analysis identified eight unique sequence alterations. We also used
      single-strand conformation polymorphism analysis to screen for mutations in the
      same fragment of the hprt gene. This analysis was less successful than denaturing
      gradient gel electrophoresis in detecting the eight unique mutations. The
      procedures described here may represent a useful approach for studying the
      mechanisms of in vivo mutation.

PMID- 7526168
TI  - Structure-mutagenicity relationships in series of 11H-indolo[3,2-c]quinoline-1,4
      diones, tetrahydro-11H-indolo[3,2-c]quinoline-1,4-diones and 11H
      pyrido[3',4':4,5]pyrrolo[3,2-c]quinoline-1,4-diones with leukemia cytotoxic
      properties. Relations with topoisomerase I inhibiting properties.
AB  - Six heterocyclic quinones with topoisomerase I inhibiting properties and
      cytotoxic activities on L1210 leukemia cells were studied for their mutagenicity
      in four strains of Salmonella typhimurium. The tested compounds are 3
      methoxyindolo[3,2-c]quinoline-1,4-diones and their derivatives in which the
      common pyrroloquinoline nucleus is annelated either with a benzene or a
      cyclohexane on a pyridine ring. Almost all quinones were found to be direct
      acting mutagens at different levels in all strains, mainly TA97a and TA98.
      Relations were established between their structure and their mutagenic
      activities. The mutagenicity was found to be influenced (i) by the nature of the
      fourth nucleus: the pyridinic compounds were the most active, the non-aromatic
      ones were practically inactive; (ii) by the presence of a methyl group in the 6
      position that decreased the mutagenicity. Then, the mutagenic properties were
      compared with the topoisomerase I inhibiting property that is one of the possible
      mechanisms of action for these cytotoxic quinones. The results indicated a
      correlation between mutagenicity and enzyme inhibiting properties.

PMID- 7526170
TI  - Series: current issues in mutagenesis and carcinogenesis, No. 51. Dose-level
      selection for in vivo genetic toxicity assays.

PMID- 7526169
TI  - Differences in the adaptive response to radiation damage in G0 human lymphocytes
      conditioned with hydrogen peroxide or low-dose X-rays.
AB  - We have carried out experiments to study the adaptive response in G0 human
      lymphocytes conditioned with either hydrogen peroxide or low-dose X-rays and
      challenged with 1.5 Gy of X-rays after stimulation. Peroxide conditioning
      treatment was given at different times before stimulation, while the low-dose
      irradiation was delivered at different dose rates just before stimulation of
      lymphocytes. A protective effect of pre-exposure to H2O2 against radiation damage
      detected as micronuclei in binucleated cells was evident, regardless of the time
      of conditioning treatment during G0. For low-dose-irradiated cells, on the other
      hand, the adaptation observed seemed to depend upon the dose rate, and never
      reached the extent observed in cells treated with peroxide.

PMID- 7526171
TI  - Sister-chromatid exchanges, chromosomal aberrations and cytotoxicity produced by
      topoisomerase II-targeted drugs in sensitive (A2780) and resistant (A2780-DX3)
      human ovarian cancer cells: correlations with the formation of DNA double-strand
      breaks.
AB  - Doxorubicin, ellipticine and etoposide are antineoplastic drugs with
      topoisomerase II inhibitory activity. The relationship between drug-induced
      sister-chromatid exchanges (SCEs) or chromosomal aberrations (CAs) and
      cytotoxicity, or drug-induced DNA double-strand breaks (DSBs) and cytotoxicity,
      or drug-induced SCEs and DSBs was investigated in human ovarian cancer cells
      sensitive (A2780) and resistant (A2780-DX3) to topoisomerase II inhibitors. 30
      min drug treatments produced SCEs, CAs and DSBs in sensitive cells, doxorubicin
      being more potent than etoposide at equimolar concentrations. The same treatments
      of resistant (A2780-DX3) cells did not produce chromosomal damage (SCEs, CAs,
      DSBs) and no cytotoxicity was observed. A plot of cytotoxicity versus SCEs
      indicated a good correlation between these two parameters for topoisomerase II
      inhibitors and not for mytomicin C. The plot of DSBs versus SCEs also showed a
      very good correlation.

PMID- 7526172
TI  - Deletions induced in the white and vermilion genes of Drosophila melanogaster by
      the antitumor drug cis-dichlorodiammineplatinum(II).
AB  - This paper describes the analysis of cisplatin induced mutations at the white (w)
      and vermilion (v) loci located on the X chromosome of Drosophila melanogaster.
      Twenty-eight w and eight v mutants have been found in a male genetic context and
      42 w mutants in a female genetic context. In these latter experiments, genetic
      analysis showed the presence of multi-locus deficiencies in 18 out of 42 w
      mutants. Eighteen w and three v intragenic mutations were analyzed at the
      molecular level. Seventeen w and three v mutants carry deletions within the gene,
      ranging in size from 4 to 109 base pairs. Sequence analysis of the mutants
      indicates that most of them were produced by non-homologous recombinational
      events occurring between short (2-5 bp) sequence repeats on both sides of the
      deletion, one repeat being retained at the new junction. These results differ
      largely from those obtained in prokaryotic and other eukaryotic cells.

PMID- 7526173
TI  - Dicentric and translocation analysis for retrospective dose estimation in humans
      exposed to ionising radiation during the Chernobyl nuclear power plant accident.
AB  - Chromosome analyses were carried out in peripheral blood lymphocytes obtained
      between September 1991 and March 1992 from 15 persons exposed to ionising
      radiation during the Chernobyl nuclear power plant accident. At present, all are
      being treated for symptoms of the delayed stage of the cutaneous radiation
      syndrome. Biological dose-equivalent estimates were determined, either by
      measuring the frequency of dicentric and ring chromosomes in first division
      unstable cells from conventional preparations (Qdr method), or by measuring the
      frequency of stable translocations using two-colour fluorescence in situ
      hybridisation (FISH) with composite whole chromosome-specific DNA libraries for
      human chromosomes 1, 4 and 12 (chromosome painting) and a degenerate alpha
      satellite pancentromeric DNA probe. With both methods fairly comparable
      individual estimates between 1.1 and 5.8 Gy were obtained for 12 of 15
      individuals. Three individuals exhibited no elevated aberration frequencies.
      Perspectives and limitations of chromosome painting for dose reconstruction of
      past radiation exposures are discussed.

PMID- 7526174
TI  - Formation and stability of acetaldehyde-induced crosslinks between poly-lysine
      and poly-deoxyguanosine.
AB  - The amino acid residue and nucleoside specificity of acetaldehyde-induced DNA
      protein crosslinks (DPXLs) were studied using a modified filter binding assay. A
      40% inhibition of acetaldehyde-induced pUC13 plasmid DNA-calf thymus histone
      crosslink formation was achieved by addition of 50 mM lysine (free base), while
      arginine was unable to affect crosslink formation at concentrations to 150 mM.
      Polymers (5-mers) of lysine (poly-lys5) were able to substitute for histones in
      acetaldehyde-induced plasmid crosslink formation, being equally effective at
      equimolar concentrations. Homopolymers (6-mers) of deoxyguanosine (poly-dG6) (but
      not deoxyadenosine, deoxycytidine or thymidine) served as an efficient substrate
      for acetaldehyde-induced DPXL formation, using either calf thymus histones or
      poly-lys5 as the protein source. Acetaldehyde-induced crosslinks between poly-dG6
      and poly-lys5 were formed rapidly, but were unstable at 37 degrees C (a half-life
      or 1.5-2 h). Stability of these crosslinks was unaffected by pH at a range of 5.5
      9.0 at 37 degrees C for 2 h. Results presented here suggest that unstable
      complexes of deoxyguanosine and lysine constitute a major portion of the DPXLs
      formed by acetaldehyde in vitro.

PMID- 7526175
TI  - Spontaneous mutations in lacI-containing lambda lysogens derived from transgenic
      mice: the observed patterns differ in liver and spleen.
AB  - The pattern of somatic mutation observed in tumor suppressor genes, such as the
      p53 gene, vary dramatically with tumor type. Some of the observed differences are
      due to tissue specific effects of mutagens, but it is also possible that some
      differences may reflect the tissue/cell type specificity of spontaneous mutation.
      Transgenic mouse models with recombinant shuttle vectors containing the lacI or
      lacZ target genes may shed light on the extent to which spontaneous mutation
      displays tissue specificity. Herein we utilize a recently described selectable
      system to obtain spontaneous mutants for analysis of the molecular lesions.
      Spontaneous mutations were isolated in the lacI gene recovered from five
      transgenic mice carrying a lambda shuttle vector. Seventy-three and 67
      independent mutations derived from liver and spleen DNA, respectively, were
      defined in the amino terminal region of lacI. Although technical barriers
      preclude a direct assessment of the E. coli derived pattern of mutation in this
      system, five pieces of circumstantial evidence suggest that many of the mutations
      arose in mouse rather than in E. coli. In DNA from both liver and spleen,
      mutations at CpG dinucleotides predominate (58% and 51%, respectively). In
      spleen, most of the mutations at CpG are transitions, while in liver most are
      transversions. In addition, liver has a higher frequency of GC-->TA transversions
      at non-CpG dinucleotides while spleen had a higher frequency of deletions and
      insertions. The data provide evidence that the spontaneous pattern of mutation is
      tissue specific. In addition, the high frequency of transversions at CpG suggests
      the need to reevaluate the mechanisms by which mutations occur at this methylated
      dinucleotide.

PMID- 7526176
TI  - Studies on the effect of ethanol on dominant lethal mutations in Swiss, C57BL6
      and CBA mice.
AB  - Swiss, C57BL6 and CBA males were given 0.1 ml of 40% ethanol per mouse per day
      for three consecutive days, intraperitoneally. These males were mated with
      untreated virgin Swiss females employing a 4-day mating schedule and three
      consecutive matings were carried out. In another study, C57BL6 males were given
      an ascending gradient of 5% to 40% ethanol in drinking water for a total period
      of 11 weeks. These males were mated with C57BL6 females for 2 weeks. Females were
      dissected at mid-term pregnancy for the examination of uterine contents including
      total, live and dead implants. All the investigations comprised at least two or
      three independent experiments which were evaluated independently as well as after
      pooling the data. Swiss, C57BL6 and CBA males given 0.1 ml of 40% ethanol,
      intraperitoneally, gave no evidence of any significant increase in post
      implantation lethality in the postmeiotic phase of spermatogenesis attributable
      to ethanol treatment. A moderate but significant reduction in mean total implants
      indicating pre-implantation losses was seen in Swiss but not in CBA mice.
      Prolonged feeding of ethanol up to 40% in drinking water failed to provide any
      evidence of dominant lethal mutations in C57BL6 males at the pre-implantation
      level and the post-implantation lethals were also not significantly higher than
      in controls. In Swiss mice, however, the mutagenic index based on both pre- and
      post-implantation lethality was consistently positive.

PMID- 7526177
TI  - Enhanced specific-locus mutation response of 101/H male mice to single, acute X
      irradiation.
AB  - The specific-locus mutation yield from 101/H mice following single, acute 6 Gy
      spermatogonial X-irradiation was significantly higher than both a concurrent
      C3H/HeH x 101/H F1 hybrid control and historical data obtained with mice of
      equivalent genotype. There is therefore discord with the reduced translocation
      response to single X-ray doses previously identified in this strain. By contrast,
      the mutation yield following a 24-h interval 3 + 3 Gy fractionated X-ray dose was
      not significantly different from that of its concurrent hybrid control, nor from
      results obtained by others with mice of the equivalent or different genotypes.
      Here there is no discord with the translocation response obtained with a 1 + 5 Gy
      24-h interval fractionated regime. Appraisal of comparable specific-locus and
      translocation data indicates that the differing results obtained with the two
      genetic end-points are not without precedence. This, together with the
      observation that the responses for cytologically visible deletions and specific
      locus mutations are similar, suggests that the latter two events predominantly
      derive from one-hit events, with translocations deriving from two-hit events and
      that the probabilities of induction of each type of lesion vary according to the
      organisation of the nucleus in different phases of the cell cycle.

PMID- 7526178
TI  - Induction of micronuclei by stilbene-type and steroidal estrogens in Syrian
      hamster embryo and ovine seminal vesicle cells in vitro.
AB  - The induction of micronuclei (MN) is a known effect of the carcinogenic estrogen
      diethylstilbestrol (DES). We have now tested the time course and dose dependence
      of MN induction by DES and its analogs 3',3"-DES, indenestrol A (IA), indenestrol
      B (IB) or by the steroidal estrogen 17 beta-estradiol (E2) and by the clastogenic
      compound 4-nitroquinoline-N-oxide (NQO) in two primary mammalian cell culture
      systems. All compounds induced MN in Syrian hamster embryo and ovine seminal
      vesicle cells with compound-specific time courses and dose dependences. DES
      induced a maximum MN frequency 12 h post treatment, whereas with all other
      estrogens the highest MN frequency was observed 3-6 h after removal of the
      compound. The maximum MN frequency after NQO treatment occurred at 24 h or later.
      Of the stilbene estrogens tested, only DES caused an increase of the mitotic
      index. Further characterization of the MN by indirect immunofluorescence
      microscopy using CREST antikinetochore antibodies revealed that 92-99% of the DES
      induced MN but only 0-2% of the NQO-induced MN contained CREST-reactive
      kinetochores. Since kinetochore-positive MN are indicative of whole
      chromosomes/chromatids and kinetochore-negative MN of acentric chromosomal
      fragments, our findings support the view that DES acts as a pure aneuploidogen
      and NQO as a pure clastogen in the two cell systems. In the case of 3',3"-DES,
      IA, IB and E2, 41-68% of the induced MN contained CREST-reactive kinetochores. As
      the time courses of MN induction are not compatible with those of clastogenic
      agents, it is proposed that these estrogens induce MN containing
      chromatids/chromosomes with altered kinetochore structures.

PMID- 7526179
TI  - Mutational spectrum of revertants in the hisD3052 allele of Salmonella
      typhimurium induced by hydrogen peroxide-activated benzidine.
AB  - Benzidine is mutagenic in a modified Ames (Salmonella typhimurium) assay, which
      uses hydrogen peroxide-dependent peroxidative activation. The mutational
      specificity of benzidine was investigated in tester strain TA98, which reverts by
      frameshifts of the hisD3052 allele. The most frequently observed mutation is a
      deletion of two bases from a (CG)4 run. This deletion was elevated in frequency
      among benzidine-induced revertants, relative to spontaneous revertants. Many
      other mutations were also observed, including additions, deletions, and complex
      events. Only small frameshifts were observed among the benzidine-induced
      revertants, whereas some larger deletions were observed among the spontaneous
      revertants.

PMID- 7526180
TI  - CHO.K1 cell mutants sensitive to active oxygen-generating agents. I. Isolation
      and genetic studies.
AB  - Nine mutants isolated from CHO.K1 cells with increased sensitivity to the lethal
      effect of plumbagin (PG), a powerful superoxide generator, were classified into
      five groups, A-E, according to their sensitivity to PG and methyl viologen (MV).
      Two mutants of group B (Pa13 and Pb4) were sensitive to both drugs, and two
      mutants of group C (Pa14 and Pa15) were moderately sensitive to PG and extremely
      sensitive to MV. To mitomycin C (MMC) these mutants showed cross-sensitivity;
      especially Pa13 and Pb4 (group B) were highly sensitive to MMC. Genetic
      complementation analyses of these four mutants were carried out using MV
      sensitivity. Sensitivity group B was divided into two complementation group, I
      and II. Pa14 and Pa15 belonged to the same complementation group III. These four
      mutants were also classified into three complementation groups for MMC
      sensitivity. Because Pa13 and Pb4 were also sensitive to cis
      diamminedichloroplatinum(II), they may have a defect in the repair of DNA
      crosslinks induced by these agents. A complementation group IV (Pa2 and Pa8) was
      also suggested based on the studies of MMC sensitivity.

PMID- 7526181
TI  - Caffeine potentiates or protects against radiation-induced DNA and chromosomal
      damage in human lymphocytes depending on temperature and concentration.
AB  - The effect of caffeine on radiation-induced chromosomal aberrations and DNA
      strand breaks in unstimulated human lymphocytes was investigated. When present
      prior to and during the radiation exposure, caffeine treatment was found to cause
      either potentiation or protection against induction of chromosomal aberrations
      depending on the concentration and temperature. When the nucleoid sedimentation
      technique was applied, enhancement or reduction of radiation-induced DNA strand
      breaks by caffeine was also found to be dependent on temperature and caffeine
      concentration. It is proposed that caffeine, in addition to its suspected ability
      to influence DNA repair, can also influence the induction of DNA damage, leading
      to alterations in the yield of chromosomal aberrations.

PMID- 7526182
TI  - DNA sequence analysis of spontaneous and gamma-radiation (anoxic)-induced lacId
      mutations in Escherichia coli umuC122::Tn5: differential requirement for umuC at
      G.C vs. A.T sites and for the production of transversions vs. transitions.
AB  - Escherichia coli umuC122::Tn5 cells were gamma-irradiated (137Cs, 750 Gy, under
      N2), and lac-constitutive mutants were produced at 36% of the wild-type level
      (the umuC strain was not deficient in spontaneous mutagenesis, and the mutational
      spectrum determined by sequencing 263 spontaneous lacId mutations was very
      similar to that for the wild-type strain). The specific nature of the umuC
      strain's partial radiation mutability was determined by sequencing 325 radiation
      induced lacId mutations. The yields of radiation-induced mutation classes in the
      umuC strain (as a percentage of the wild-type yield) were: 80% for A.T-->G.C
      transitions, 70% for multi-base additions, 60% for single-base deletions, 53% for
      A.T-->C.G transversions, 36% for G.C-->A.T transitions, 25% for multi-base
      deletions, 21% for A.T-->T.A transversions, 11% for G.C-->C.G transversions, 9%
      for G.C-->T.A transversions, and 0% for multiple mutations. Based on these
      deficiencies and other factors, it is concluded that the umuC strain is near
      normal for A.T-->G.C. transitions, single-base deletions and possibly A.T-->C.G
      transversions; is generally deficient for mutagenesis at G.C sites and for
      transversions, and is grossly deficient in multiple mutations. Damage at G.C
      sites seems more difficult for translesion DNA synthesis to bypass than damage at
      A.T sites, and especially when trying to produce a transversion. The yield of G.C
      ->A.T transitions in the umuC strain (36% of the wild-type level) argues that
      abasic sites are involved in no more than 64% of gamma-radiation-induced base
      substitutions in the wild-type strain. Altogether, these data suggest that the
      UmuC and UmuD' proteins facilitate, rather than being absolutely required for,
      translesion DNA synthesis; with the degree of facilitation being dependent both
      on the nature of the noncoding DNA damage, i.e., at G.C vs. A.T sites, and on the
      nature of the misincorporated base, i.e., whether it induces transversions or
      transitions.

PMID- 7526183
TI  - Induction of chromosome aberrations in Syrian hamster renal cortical cells by
      various estrogens.
AB  - Estrogens, both natural and synthetic, have been implicated in carcinogenesis at
      different organ sites in a variety of animals, including man, for more than six
      decades. However, the molecular mechanism(s) involved in the carcinogenic action
      of estrogens still remains both controversial and elusive. Cytogenetic damage in
      the hamster kidney has been studied after in vivo treatment with either potent or
      weak estrogens for varying periods. Compared to age-matched untreated control,
      diethylstilbestrol (DES) treatment resulted in significant increases in the
      number of chromatid gaps and breaks, chromosome breaks, and endoreduplicated
      cells in hamster renal cortical cells. These chromosomal aberrations (CA) were
      cumulative with continued hormone exposure from 1.0 to 5.0 months. However,
      chromosome exchanges as a result of the breaks were not elevated. After 5.0
      months of hormone treatment, potent estrogens such as 17 beta-estradiol and
      Moxestrol exhibited similar frequencies of CA in the hamster kidney to that found
      for DES, whereas weak estrogens such as 17 alpha-estradiol and beta-dienestrol
      exhibited CA frequencies that were not significantly different from untreated
      levels. Ethinylestradiol treatment for a similar period resulted in significant
      increases in chromatid gaps, although these did not evolve into increases in
      either chromatid or chromosome breaks, and in a rise in endoreduplicated cells.
      These results raise the possibility that the CA generated after estrogen
      treatment may be involved in renal tumorigenic processes.

PMID- 7526184
TI  - Damage and mutagenesis of E. coli and bacteriophage lambda induced by oxathiolane
      and aziridinyl steroids.
AB  - lambda-Escherichia coli complexes exhibited remarkable sensitivity to the
      treatment with test steroidal derivatives in the presence of Cu(II). The decline
      in plaque-forming units after steroid treatment was more pronounced in complexes
      with some of the radiation repair-defective mutants of E. coli K-12, i.e., recA,
      lexA and polA, as compared to uvrA and wild-type strains. The red gene of lambda
      phage and recA gene of E. coli seem to have a complementary effect on the steroid
      induced lesions. An enhanced level of mutagenesis was observed when steroid
      treated E. coli cells were transformed with steroid-treated pBR322 plasmid DNA. A
      remarkable degree of c mutation was also observed when steroid I-treated phage
      particles were allowed to adsorb on steroid-treated wild-type bacteria. Moreover,
      the oxathiolane steroid treatment of lambda cI857-E. coli lysogen resulted in
      prophage induction in nutrient broth even at 32 degrees C. Thus on the basis of
      these results, the role of SOS repair system in steroid-induced mutagenesis and
      repair of DNA lesions in E. coli and bacteriophage lambda has been suggested.

PMID- 7526185
TI  - Calcium chelator Quin-2 prevents crocidolite-induced DNA strand breakage in human
      white blood cells.
AB  - Exposure of human white blood cells to UICC crocidolite asbestos in vitro
      resulted in the formation of DNA strand breakage in a dose-dependent manner up to
      a fibre concentration of 100 micrograms/ml. Subsequent incubations with the iron
      chelator desferrioxamine or the intracellular Ca2+ chelator Quin-2 prevented DNA
      strand break formation above control incubations. Addition of aurintricarboxylic
      acid, an endonuclease inhibitor, similarly abolished crocidolite-induced DNA
      strand breaks in these cells. These results suggest that crocidolite-derived
      hydroxyl radicals do not directly induce DNA strand breakage in mammalian white
      blood cells. In order to assess Ca2+ mobilisation from intracellular stores in
      control and crocidolite-treated cells, the fullness of these stores was measured
      by treating with thapsigargin, a specific inhibitor of the endoplasmic reticulum
      Ca(2+)-ATPase. On addition of thapsigargin to fura-2AM-loaded cells treated with
      crocidolite we demonstrated that the endoplasmic reticulum stores had been
      depleted as no further Ca2+ was released, unlike control cells. We suggest that
      strand breakage is caused by a complex set of events involving oxygen free
      radicals that may disturb intracellular Ca2+ homoeostasis and the breaks are
      produced by secondary reactions, involving Ca(2+)-mediated enzymes.

PMID- 7526186
TI  - The induction of chromosomal damage and cell killing in mouse spermatogonial stem
      cells following combined treatments with hydroxyurea, 3-aminobenzamide and X
      rays.
AB  - To analyze in more detail the relation between the sensitivity of spermatogonial
      stem cells to killing and the induction of genetic damage, mature male mice
      received combined treatments with hydroxyurea (HU), 3-amino-benzamide (3-AB) and
      X-rays. Stem cell killing was determined using the repopulation index method and
      translocations were studied via spermatocyte analysis. HU was administered at 16
      or at 48 h before further treatment in order to create stem cell populations with
      different sensitivities in which the translocation induction and stem cell
      killing could be studied and compared. The sensitivities for cell death and
      genetic damage appeared to be strongly correlated: at 16 h after HU significantly
      higher values were found than at 48 h or in controls without HU pretreatment. By
      using 3-AB in the treatment schedules we were able to investigate whether the
      sensitization of stem cells towards cell death and genetic damage is the outcome
      of a radiation- or drug-induced G1 delay. The effect of 3-AB was most pronounced
      at 16 h after HU. This confirms that at this interval a large fraction of stem
      cells is in G1. Our data therefore indicate that all treatments that induce an
      enrichment of G1 cells also result in a sensitization of stem cells to cell
      killing or the induction of mutagenic damage.

PMID- 7526187
TI  - Anticlastogenic effects of galangin against bleomycin-induced chromosomal
      aberrations in mouse spleen lymphocytes.
AB  - Galangin, a flavonoid derivative, was tested for its anticlastogenic effect
      against the induction of chromosome aberrations by bleomycin. For an in vitro
      assay, galangin (0, 2 x 10(-8), 2 x 10(-7), and 2 x 10(-6) M) was added to mouse
      spleen lymphocyte cultures together with bleomycin (3 microgram/ml) at 24 h after
      Con A initiation of cultures. In an in vivo/in vitro experiment, galangin (0,
      0.1, 1, 10, and 100 mg/kg) was administered to mice orally twice with a 24-h
      interval. Mice were killed 8 h later. Spleen lymphocytes were isolated and
      cultures were made. Bleomycin (3 microgram/ml) was added to the mouse spleen
      lymphocyte cultures at 24 h after Con A initiation. Both in vitro and in vivo/in
      vitro cultures were harvested at 42 h after initiation. The harvested cells were
      used for cytogenetic analyses. The results showed that in vitro or in vivo
      treatment of lymphocytes with galangin suppressed the induction of chromosome
      aberrations by bleomycin in a galangin dose-dependent manner. The galangin doses
      used were non-clastogenic to cells. The data from our in vitro and in vivo/in
      vitro studies confirmed each other and indicate that galangin is an
      anticlastogenic agent. The in vivo/in vitro protocol may be a useful means to
      assay the chemoprotective effects of chemicals in humans.

PMID- 7526188
TI  - Micronuclei and 3AB index in X-irradiated human lymphocytes in G0 and G1 phases.
AB  - We applied the cytokines-block micronucleus assay to observe the radiobiological
      response of human lymphocytes after X-ray treatment in the G0 and G1 phases. In
      addition, we used 3-aminobenzamide (3AB) to measure the 3AB index in the two
      phases. The experimental results show that at 2 Gy the MN yield and the 3AB index
      are dependent on the cell phase and show considerable inter-individual
      variability. The radiation-induced MN frequency obtained for 33 subjects is 0.470
      +/- 0.063 for the G0 phase and 0.689 +/- 0.139 for the G1 phase; the 3AB index
      values are 0.326 +/- 0.144 and 0.067 +/- 0.058 for G0 and G1 phases,
      respectively. At the individual level, the 3AB index for the G1 phase correlates
      inversely with the cytogenetic effects observed in that phase. We discuss the
      possibility of applying the MN test combined with the 3AB index to lymphocytes at
      different phases to study the individual response to radiation (individual
      radiosensitivity).

PMID- 7526189
TI  - Binding of mutagenic heterocyclic amines by intestinal and lactic acid bacteria.
AB  - Lactic acid bacteria have been reported to have antimutagenic/anticarcinogenic
      properties in vitro and in vivo. One possible mechanism for this effect involves
      a physical binding of the mutagenic compounds to the bacteria. The purpose of the
      present investigation was to study the binding capacity of eight human intestinal
      or lactic acid bacterial strains for mutagenic heterocyclic amines formed during
      cooking of protein-rich food. Binding of the mutagens Trp-P-2, PhIP, IQ and MeIQx
      by the bacterial strains was analyzed by HPLC. There were only minor differences
      in the binding capacities of the tested strains but the mutagenic compounds were
      bound with markedly different efficiencies. Trp-P-2 was almost completely bound
      and the binding tended not to be of a reversible nature. The binding of PhIP,
      which reached about 50%, was important as PhIP is a major mutagen in the western
      diet. IQ and MeIQx were slightly less well bound. pH appeared to be of importance
      for the binding efficacy. Binding correlated well with the reduction in
      mutagenicity observed after exposure of the heterocyclic amines to the bacterial
      strains. The results indicate that cooked food mutagenic compounds, commonly
      found in the western meat-rich diet, can be bound to bacteria from the normal
      intestinal microflora in vitro.

PMID- 7526190
TI  - Diminution of singlet oxygen-induced DNA damage by curcumin and related
      antioxidants.
AB  - Curcumin, the natural antioxidant from turmeric, an Indian spice, and its
      derivatives have significant abilities to protect plasmid pBR322 DNA against
      single-strand breaks induced by singlet oxygen (1O2), a reactive oxygen species
      with potential genotoxic/mutagenic properties. 1O2 was generated at 37 degrees C
      in an aqueous buffer system by the thermal dissociation of the endoperoxide of
      3,3'-(1,4-naphthylene)dipropionate (NDPO2). Among the compounds tested, curcumin
      was the most effective inhibitor of DNA damage followed by desmethoxycurcumin,
      bisdesmethoxycurcumin and other derivatives. The observed antioxidant activity
      was both time- and concentration-dependent. The protective ability of curcumin
      was higher than that of the well-known biological antioxidants lipoate, alpha
      tocopherol and beta-carotene. However, the highest protective ability with
      saturating concentrations of curcumin did not exceed 50%. The ability of curcumin
      and its derivatives to protect DNA against 1O2 seems to be related to their
      structures and may at least partly explain the therapeutic and other beneficial
      effects of these compounds including anticarcinogenic and antimutagenic
      properties.

PMID- 7526191
TI  - Processing of MucA protein is required for spontaneous and benzo[a]pyrene-induced
      reversion of the Escherichia coli trpA23 missense mutation by G.C-T.A
      transversions: effect of a deficiency in the MutY DNA glycosylase.
AB  - We have studied the influence of the processing of MucA protein on the occurrence
      of base substitution mutations. Escherichia coli strains carrying the trpA23
      missense mutation and having a full deletion of the chromosomal umuD/C operon
      were transformed with plasmids encoding the MucB protein together with either
      wild-type MucA or the nonprocessable MucA202 protein. The efficient reversion of
      the trpA23 allele by G.C-T.A transversions in benzo[a]pyrene (B[a]P)-treated
      cells required the function of a matured MucA protein. This processed protein was
      also necessary for the occurrence of G.C-T.A transversions targeted at
      spontaneous DNA lesions and for the SOS mutator effect dependent on the
      constitutive coprotease activity of the RecA730 protein. In contrast, G.C-T.A
      transversions reverting trpA23 were spontaneously generated by an SOS-independent
      mechanism in cells deficient in the MutY DNA glycosylase.

PMID- 7526192
TI  - Post-irradiation DNA synthesis inhibition and G2 phase delay in radiosensitive
      body cells from non-Hodgkin's lymphoma patients: an indication of cell cycle
      defects.
AB  - In the present study, both post-irradiation DNA synthesis and G2 phase
      accumulation were analyzed in lymphoblastoid cell lines (LCLs) and fibroblast
      cell strains derived from (Saudi) patients with non-Hodgkin's lymphoma (NHL),
      ataxia telangiectasia (AT), AT heterozygotes and normal subjects. A comparison of
      the percent DNA synthesis inhibition (assayed by 3H-thymidine uptake 30 min after
      irradiation), and a 24 h post-irradiation G2 phase accumulation determined by
      flow cytometry placed the AT heterozygotes and the NHL patients in an
      intermediate position between the normal subjects (with maximum DNA synthesis
      inhibition and minimum G2 phase accumulation) and the AT homozygotes (with
      minimum DNA synthesis inhibition and maximum G2 accumulation). The similarity
      between AT heterozygotes and the NHL patients with respect to the two parameters
      studied after irradiation was statistically significant. The data indicating a
      moderate abnormality in the control of cell cycle progression after irradiation
      in the LCLs and fibroblasts from NHL patients may explain the enhanced cellular
      and chromosomal radiosensitivity in these patients reported by us earlier. In
      addition to demonstrating a link between cell cycle abnormality and
      radiosensitivity as a possible basis for cancer susceptibility, particularly in
      the NHL patients, the present studies emphasized the usefulness of the assay for
      24 h post-irradiation G2 phase accumulation developed by Lavin et al. (1992) in
      characterizing AT heterozygote-like cell cycle anomaly in cancer patients
      irrespective of whether they carried the AT gene or any other affecting the cell
      cycle.

PMID- 7526193
TI  - DNA damage and topoisomerase II inhibition induced by a benzopsoralen derivative.
AB  - The ability of 4-hydroxymethyl-4',5'-benzopsoralen (HMBP) to damage DNA of
      Chinese hamster ovary cells (CHO) and to inhibit the activity of topoisomerase II
      in vitro has been studied. This compound is characterized by a fourth ring
      condensed at the furan-side in the psoralen molecule. Contrary to other known
      furocoumarin derivatives, HMBP induces chromosomal aberrations in mammalian cells
      without UVA activation. The lesions induced in the dark by HMBP in DNA were
      studied by alkaline and neutral elution in CHO cells; comparable amounts of
      single-strand breaks and DNA-protein cross-links as well as the formation of
      double-strand breaks were detected. Moreover, HMBP appeared to inhibit the
      activity of mammalian topoisomerase II in vitro, in both the catenation and the
      decatenation assay. In these experiments the drug was effective only when it was
      pre-incubated with DNA substrate. These results are also consistent with the
      cytotoxic and mutagenic activity of HMBP in the dark, as tested on V79 Chinese
      hamster cells (V79/HGPRT system).

PMID- 7526194
TI  - Effects of prostaglandin E2 on the micronucleus formation in mouse bone marrow
      cells by various mutagens.
AB  - The effects of prostaglandin E2 (PGE2), as a trigger of erythroid progenitor
      cells into the cell cycle, were studied on the induction of micronuclei by
      various mutagens; with mitomicin C (MMC) the optimal protocol was established.
      PGE2 itself did not induce any micronuclei in this experiment. The highest
      frequency of micronuclei and dose-response relationship between PGE2 doses and
      micronucleus frequency were observed 30 h after injection of MMC to mice
      administered PGE2 24 h previously. Sensitization by PGE2 pretreatment was also
      found for other mutagens, such as vincristine, 5-fluorouracil, benzo[a]pyrene,
      1,1-dimethylhydrazine and 2-naphthylamine. These results support the hypothesis
      that accelerating the erythropoiesis increases the frequency of micronuclei
      induced by mutagens.

PMID- 7526195
TI  - Effects of DNA repair deficiency on the mutational specificity in the lacZ gene
      of Escherichia coli.
AB  - The mutational specificities of various chemical mutagens were compared in
      isogenic E. coli strains with different DNA repair capabilities (wild-type, uvrA,
      umuC, and uvrA umuC) in a reversion assay employing a set of mutant lacZ genes
      that can detect two types of transitions, four types of transversions, and five
      kinds of specific frameshift events. A uvrA derivative was more sensitive than
      the wild-type strain to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone for
      +1G, -1G, -2(C-G), +1A and -1A frameshifts, G.C-->A.T transitions, and G.C-->T.A
      transversions. In a uvrA background, G.C-->T.A transversions and +1G, +1A, and 
      1A frameshifts appeared to be umuC-dependent, while G.C-->A.T transitions were
      not. N-Ethyl-N'-nitro-N-nitrosoguanidine was more mutagenic in a uvrA background
      for five kinds of frameshifts and G.C-->A.T transitions, but not for G.C-->T.A,
      A.T-->C.G, and A.T-->G.C base substitutions. A.T-->C.G transversions were totally
      dependent on umuC gene function. For the investigation of mutational
      specificities induced by frameshift mutagens, an rfa mutation was additionally
      introduced. The rfa strain responded to 2-nitrofluorene, which induced primarily 
      2(C-G) frameshift mutations. In an rfa uvrA background, benzo[a]pyrene induced
      +1G, -1G, +1A, and -1A frameshifts. 2-Aminoanthracene induced +1G, -1G, and +1A,
      but not -1A, frameshifts, with -1G frameshifts predominating. Ethidium bromide
      induced only two types of frameshifts, -1G and +1A. Frameshifts induced by ICR
      170 were independent of umuC gene function, while those by induced 1-nitropyrene
      were partly umuC-dependent.

PMID- 7526196
TI  - High recombinagenic activities of three antiviral agents, adenine derivatives, in
      the Drosophila wing spot test.
AB  - Three adenine derivatives, (R,S)-9-(2,3-dihydroxypropyl)adenine (DHPA), D
      eritadenine (EA), and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), prospective
      antiviral drugs, were subjected to genotoxicity analysis using the somatic
      mutation and recombination test in Drosophila melanogaster. All three compounds
      were found to be very potent inducers of mosaic spots on Drosophila wings in a
      dose-related fashion. Data obtained in inversion-free flies revealed that the
      compounds, in particular DHPA and EA (nucleoside analogues), are highly effective
      in the induction of mitotic recombination. PMEA, a nucleotide analogue, exhibited
      a rather different genotoxic profile from those of DHPA and EA, indicating a
      different mechanism of genetic action of this compound. Of somatic mutations,
      chromosome aberrations rather than point mutations seem to play a major role in
      the genotoxicity of PMEA. In flies carrying an inversion chromosome, which
      eliminates most products of mitotic recombination, reduced spot frequencies were
      obtained, which, however, were still unexpectedly high for compounds with strong
      recombinagenic activities. Most probably, in addition to structural mutations of
      chromosome, double mitotic crossing-over and non-reciprocal recombination events
      similar to unequal sister-strand recombination or gene conversion significantly
      contributed to spot induction in the inversion heterozygous flies. Concerning the
      mechanism of genotoxic action, we suggest that these adenine derivatives can be
      incorporated into DNA chains during replication. This would result, via breaks
      and DNA repair mechanisms, either in various recombination events or in
      chromosome aberrations.

PMID- 7526197
TI  - Synaptonemal complex damage in fetal mouse oocytes induced by ionizing
      irradiation.
AB  - Fetal female mice were exposed to ionizing irradiation of 2 Gy in a single dose
      at days 14, 16, and 17 of gestation. Synaptonemal complexes of primary oocytes
      were analyzed on day 17. It has been demonstrated that electron beam irradiation
      of early oocytes on day 14 with 2 Gy is accompanied by a duplication of atretic
      cells. A significant increase in fragmentations of the synaptonemal complexes
      over the base level became evident when mice were exposed to irradiation on days
      16 and 17 of gestation. Frequencies of multivalent formation and univalents were
      not increased over the levels in the control group. Reduction of fertility and
      malsegregation of chromosomes may be a reflection of the consequences of the
      observed nuclear lesions.

PMID- 7526198
TI  - Intracellular localization and function of DNA repair methyltransferase in human
      cells.
AB  - An antibody preparation specific for human O6-methylguanine-DNA methyltransferase
      (EC 2.1.1.63) was obtained by immunoaffinity purification on two types of
      affinity columns with the purified human and mouse methyltransferase proteins as
      ligands. The antibodies were used in Western blotting analysis of fractionated
      cell extracts. More than 90% of the methyltransferase protein was recovered in
      the cytoplasmic fractions with both human HeLa S3 cells and MR-M cells, the
      latter overproducing the enzyme 36 times as much as the former. Cytoplasmic
      localization of the methyltransferase in HeLa S3 cells was further confirmed by
      in situ immunostaining. By Western blotting analysis of fractionated cell
      extracts from HeLa S3 cells treated with alkylating agents, we found that amounts
      of the enzyme decreased more rapidly in the nuclear fraction than in the
      cytoplasmic fraction, and recovery of the enzyme level in the cytoplasmic
      fraction was slower than that in the other. These results suggest that the
      methyltransferase protein is degraded in the nucleus after it commits the repair
      reaction and that the cytoplasmic enzyme is transported into the nucleus as the
      nuclear methyltransferase is used up in this manner.

PMID- 7526199
TI  - High-level expression of the photorepair gene in Drosophila ovary and its
      evolutionary implications.
AB  - DNA photolyase catalyzes light-dependent repair of cis, syn-cyclobutane
      dipyrimidines (pyrimidine dimers); its apoenzyme is encoded by the photorepair
      (phr) gene. The phr cDNA was cloned from D. melanogaster; it has an open reading
      frame to encode a 61,483-Da protein. The phr cDNA hybridized to band 44C-D of
      Drosophila polytene chromosome, equivalent to the locus of the phr- gene.
      Drosophila photolyase is made of an apoenzyme with a molecular weight of 62 kDa.
      Drosophila photolyase is extraordinarily abundant in the embryo and adult ovary,
      whereas mRNA of the phr gene is abundant only in the ovary. The action spectrum
      of Drosophila photolyase for photoreactivation has a maximum at 440 nm. The phr
      gene of Drosophila has about 60% identical amino acid sites with that of goldfish
      but only 13-18% with those of microorganisms. Implications of the unique
      characteristics of the Drosophila phr gene are discussed overviewing the
      diversified characteristics of phr genes in various organisms that have
      presumably evolved from a common ancestral gene.

PMID- 7526200
TI  - The XPA protein is a zinc metalloprotein with an ability to recognize various
      kinds of DNA damage.
AB  - The XPA (xeroderma pigmentosum group A) gene encodes a protein of 273 amino acids
      with a zinc finger motif. The human XPA cDNA was placed in an Escherichia coli
      expression vector for the synthesis of the recombinant XPA protein. The molecular
      weight of the wild-type protein was about 40 kDa in SDS-PAGE. Microinjection of
      the wild-type protein specifically restored the defect of UV-induced unscheduled
      DNA synthesis in XP-A cells. Thus, the bacterially expressed XPA protein retains
      biochemical properties identical to those of natural sources. The wild-type
      protein binds preferentially to UV-, cis-diamminedichloroplatinum(II) (cisplatin)
      or osmium tetroxide (OsO4)-damaged DNA as assayed by retention on nitrocellulose
      filters. In addition, the data from atomic absorption and UV-CD spectra revealed
      that the wild-type protein is a zinc metalloprotein with secondary structure.
      Furthermore, the mutant protein, of which the cysteine-103 residue in the zinc
      finger motif was replaced with serine, has a vastly different protein
      conformation resulting in a loss of XP-A correcting and DNA-binding activities.
      These findings indicate that the XPA protein is a zinc-binding protein with
      affinity for various DNA damages, and a cysteine residue in the C4-type zinc
      finger motif is indispensable for normal protein conformation.

PMID- 7526201
TI  - Complementation of V(D)J recombination defect and X-ray sensitivity of scid mouse
      cells by human chromosome 8.
AB  - Cells derived from mice homozygous for the severe combined immune deficiency
      (scid) mutation exhibit hypersensitivity to ionizing radiation, and defects in
      DNA double-strand break repair and V(D)J recombination. Using the technique of
      microcell-mediated chromosome transfer, we have introduced a number of dominantly
      marked human chromosomes into scid cells to localize the human homolog of the
      murine scid gene. Analysis of human-scid hybrid clones revealed that the presence
      of human chromosome 8 partially restored accurate V(D)J recombination and
      radioresistance to scid cells. Subsequent loss of the human chromosome 8 from
      human-scid hybrid clones rendered these cells sensitive to gamma-radiation and
      impaired their ability to catalyse V(D)J recombination. Introduction of
      chromosomes 2, 14, 16 and 19 that encode other repair genes did not result in the
      correction of these two scid defects. These observations demonstrate that the
      human homolog of the mouse scid gene resides on human chromosome 8.

PMID- 7526202
TI  - Mutagenesis and epistatic grouping of the Neurospora meiotic mutants, mei-2 and
      mei-3, which are sensitive to mutagens.
AB  - To understand the possible roles of the Neurospora meiotic genes mei-2 and mei-3
      in DNA repair, the frequencies of spontaneous and UV-induced mutation at the ad-3
      loci were investigated and double mutants between mei mutants and other DNA
      repair mutants were analyzed for mutagen sensitivity. Spontaneous mutation
      frequency in mei-2 was similar to that of the wild type, while the frequencies
      were high in both of two mei-3 strains which contained different mei-3 alleles.
      In addition, the frequency of spontaneous mutation in mei-3 varied greatly from
      experiment to experiment, which clearly showed a mutator phenotype for mei-3
      mutation. UV irradiation increased mutation frequencies in both mei-2 and mei-3.
      The mutagen sensitivity of the double mutant, mei-2 mei-3, was no greater than
      that of the single mutants when treated with UV and methyl methanesulfonate
      (MMS). Thus, both mei genes appear to be involved in the same repair group. When
      analyzed in combination with other mutations, both mei mutations showed an
      epistatic relationship to uvs-6 and a synergistic relationship to mus-18 and uvs
      2. However, uvs-3 was epistatic to mei-2, but the relationship of uvs-3 to mei-3
      could not be tested directly, because the double mutant was barely viable. These
      results indicate that mei-2 and mei-3 are involved in the same repair group as
      uvs-6, and uvs-3 is possibly involved in the same group. Alternatively, the mei
      genes, or uvs-3 itself, may be related to more than one DNA repair group.

PMID- 7526203
TI  - Repair of 6-4 photoproducts and cyclobutane pyrimidine dimers in rad mutants of
      Saccharomyces cerevisiae.
AB  - Repair rates of both pyrimidine-pyrimidone (6-4) photoproducts and cyclobutane
      pyrimidine dimers have been measured in the UV-sensitive mutants of Saccharomyces
      cerevisiae: rad1 to rad12 and rad14 to rad24. A dot blot immunoassay for UV
      photoproducts was used which measures lesions in the genome as a whole and which
      distinguishes 6-4 photoproducts from cyclobutane dimers. The principal findings
      are: (1) Wild-type yeast cells, like normal mammalian cells, repair 6-4
      photoproducts more rapidly than cyclobutane dimers. (2) All mutants that are
      defective in repair are defective in repair of both lesions. (3) The most
      sensitive alleles of rad1, rad2, rad3, rad4 and rad10 show no repair of either
      lesion. (4) Leaky alleles of rad1, rad3 and rad14 show a very marked difference
      in repair rates of the two lesions, rather like the human XPA revertant cell line
      XP129 and the Chinese hamster mutants UV61 and V-H1. (5) No mutant repairs
      cyclobutane dimers more rapidly than 6-4 photoproducts.

PMID- 7526204
TI  - A single amino acid change in SNM1-encoded protein leads to thermoconditional
      deficiency for DNA cross-link repair in Saccharomyces cerevisiae.
AB  - Molecular characterization of a thermoconditional mutant snm1-2ts shows that the
      coding sequence contains three mutations, two of which are silent. The third
      changes amino acid glycine to arginine at position 256 thereby altering a
      hydrophilic domain of the protein. While sensitivity to nitrogen mustard of the
      mutant at 36 degrees C is very similar to that of the non-leaky allele snm1-1,
      multi-copy vector-mediated overexpression of snm1-2ts leads to a significantly
      reduced sensitivity to nitrogen mustard.

PMID- 7526205
TI  - Roles for the yeast RAD18 and RAD52 DNA repair genes in UV mutagenesis.
AB  - Experimental evidence indicates that although the Saccharomyces cerevisiae RAD18
      and RAD52 genes are not required for nucleotide excision repair, they function in
      the processing of UV-induced DNA damage in yeast. Conflicting statements
      regarding the UV mutability of strains deleted for RAD18 prompted us to re
      examine the influence of RAD18, and RAD52, on UV mutagenesis. To do so, we
      characterized mutations induced by UV in SUP4-o, a yeast suppressor tRNA gene.
      SUP4-o was maintained on a plasmid in isogenic strains that either carried one of
      two different rad18 deletions (rad18 delta) or had RAD52 disrupted. Both rad18
      deletions decreased the frequency of UV-induced SUP4-o mutations to levels close
      to those for spontaneous mutagenesis in the rad18 delta backgrounds, and
      prevented a net increase in mutant yield. A detailed analysis of mutations
      isolated after UV irradiation of one of the rad18 delta strains uncovered little
      evidence of the specificity features typical for UV mutagenesis in the isogenic
      repair-proficient (RAD) parent (e.g., predominance of G.C-->A.T transitions).
      Evidently, UV induction of SUP4-o mutations is highly dependent on the RAD18
      gene. Compared to the RAD strain, disruption of RAD52 reduced the frequency and
      yield of UV mutagenesis by about two-thirds. Closer inspection revealed that 80%
      of this reduction was due to a decrease in the frequency of G.C-->A.T
      transitions. In addition, there were differences in the distributions and site
      specificities of single base-pair substitutions. Thus, RAD52 also participates in
      UV mutagenesis of a plasmid-borne gene in yeast, but to a lesser extent than
      RAD18.

PMID- 7526206
TI  - Cloning of human and mouse genes homologous to RAD52, a yeast gene involved in
      DNA repair and recombination.
AB  - The RAD52 gene of Saccharomyces cerevisiae is required for recombinational repair
      of double-strand breaks. Using degenerate oligonucleotides based on conserved
      amino acid sequences of RAD52 and rad22, its counterpart from Schizosaccharomyces
      pombe, RAD52 homologs from man and mouse were cloned by the polymerase chain
      reaction. DNA sequence analysis revealed an open reading frame of 418 amino acids
      for the human RAD52 homolog and of 420 amino acid residues for the mouse
      counterpart. The identity between the two proteins is 69% and the overall
      similarity 80%. The homology of the mammalian proteins with their counterparts
      from yeast is primarily concentrated in the N-terminal region. Low amounts of
      RAD52 RNA were observed in adult mouse tissues. A relatively high level of gene
      expression was observed in testis and thymus, suggesting that the mammalian RAD52
      protein, like its homolog from yeast, plays a role in recombination. The mouse
      RAD52 gene is located near the tip of chromosome 6 in region G3. The human
      equivalent maps to region p13.3 of chromosome 12. Until now, this human
      chromosome has not been implicated in any of the rodent mutants with a defect in
      the repair of double-strand breaks.

PMID- 7526207
TI  - Patch-clamp analysis of the properties of acetylcholine receptor channels at the
      normal human endplate.
AB  - Normative data were obtained on the kinetic properties of the acetylcholine
      receptor (AChR) channel at the human motor endplate by patch-clamp analysis.
      Single channel currents were recorded from 34 endplates of 8 nonweak subjects in
      the presence of 1 micron acetylcholine (ACh) at 22 +/- 0.5 degrees C. The vast
      majority of channels opened to a conductance of about 60 pS. The dwell-time
      distributions of these channels were well described as the sum of two exponential
      functions. The mean duration of the dominant longer component was 1.9 ms for the
      open intervals and 3.04 ms for the bursts. At three endplates, a small proportion
      of the channels had lower conductance and longer open time, resembling immature
      AChR channels. At 28 endplates it was also possible to obtain an estimate of the
      rate constant for channel closure (alpha) and approximate estimates for the rate
      constants of channel opening (beta) and ACh dissociation (k-2). Estimates of k-2
      varied by 15% with methods of estimation. This is attributed to errors inherent
      in estimating the duration of the briefest channel events. The normative data
      will be useful for evaluating pathologic alterations in the kinetic properties of
      the AChR channel found in some congenital myasthenic syndromes.

PMID- 7526208
TI  - Very efficient myoblast allotransplantation in mice under FK506
      immunosuppression.
AB  - Transgenic CD1 mice expressing beta-galactosidase were used as myoblast donors.
      The myoblasts were injected in normal or mdx muscles previously irradiated and
      injected with notexin. Twenty-eight days after myoblast transplantation, the
      percentage of muscle fibers beta-glactosidase-positive was low in mice not
      immunosuppressed but was high (80%) in those treated with FK506. In mdx mice,
      muscle fibers expressing beta-galactosidase were also dystrophin positive. Most
      of the mice not treated with FK506 produced antibodies against the donor
      myoblasts. These results indicate that FK506 is a very useful immunosuppressive
      drug for myoblast transplantation in mice. Irradiation and notexin injection used
      in our experiments are, however, not feasible in humans. Other manipulations
      capable of increasing the participation of donor myoblasts to regeneration will
      therefore have to be identified before new clinical trials are attempted.

PMID- 7526209
TI  - Molecular analysis of antigens targeted by protective antibodies in rapid
      expulsion of Trichinella spiralis.
AB  - Rapid expulsion is a protective immune mechanism which eliminates as much as 99%
      of a challenge infection of Trichinella spiralis muscle larvae from the
      gastrointestinal tract of suckling rats. Protective monoclonal antibodies (mAbs)
      generated against larval excretory-secretory antigens (ESA) specifically
      recognize a 45-kDa glycoprotein, gp45, in addition to a distinct profile of other
      cross-reactive antigens that are also recognized by non-protective mAbs. Recent
      data indicate that protective mAbs recognize carbohydrate epitopes. To complement
      biochemical studies on the target(s) of rapid expulsion, we describe here the
      cloning and characterization of the cDNA, TspE1, which belongs to a multigene
      family and encodes several larval proteins in the 40-50-kDa range. A second cDNA,
      TspM6 encodes a 45-kDa antigen and is homologous to the published sequence of
      gp45. Anti-TspE1 antibodies detected antigens within beta- and gamma-stichocytes
      while anti-TspM6 antibodies detected antigens within alpha-stichocytes of the
      secretory organs of muscle larvae. Sequence analysis has provided no functional
      information on the encoded gene products. Neither recombinant antigen is
      recognized by the mAbs but native parasite molecules with peptide homology to
      both the TspE1 and TspM6 recombinant antigens bear the glycan recognized by the
      protective mAbs. These molecules are candidate targets in rapid expulsion.

PMID- 7526210
TI  - Genetic and clinical mosaicism in a type of epidermal nevus.
AB  - BACKGROUND: Many skin disorders are characterized by a mosaic pattern, often with
      alternating stripes of affected and unaffected skin that follow the lines of
      Blaschko. These nonrandom patterns may be caused by a postzygotic mutation during
      embryogenesis. We studied the genetic basis of one such disorder, epidermal nevus
      of the epidermolytic hyperkeratotic type. Epidermolytic hyperkeratosis is an
      autosomal dominant blistering skin disease arising from mutations in the genes
      for keratin (K) 1 and 10. The offspring of patients with epidermal nevi may have
      generalized epidermolytic hyperkeratosis. METHODS: We studied the K1 and K10
      genes in blood and in the keratinocytes and fibroblasts of lesional and
      nonlesional skin from three patients with epidermal nevi and four of their
      offspring with epidermolytic hyperkeratosis. RESULTS: In the patients with
      epidermal nevi, point mutations in 50 percent of the K10 alleles of epidermal
      cells were found in keratinocytes from lesional skin; no mutations were detected
      in normal skin. This mutation was absent or underrepresented in blood and skin
      fibroblasts. In the offspring with epidermolytic hyperkeratosis, the same
      mutations as those in the parents were found in 50 percent of the K10 alleles
      from all cell types examined. CONCLUSIONS: Epidermal nevus of the epidermolytic
      hyperkeratotic type is a mosaic genetic disorder of suprabasal keratin. The
      correlation of mutations in the K10 gene with lesional skin and the correlation
      of the normal gene with normal skin provide evidence that genetic mosaicism can
      cause clinical mosaicism.

PMID- 7526211
TI  - Laundry brighteners and amebic cysts.

PMID- 7526213
TI  - Vascular endothelial growth factor--its role in retinal vascular proliferation.

PMID- 7526212
TI  - Vascular endothelial growth factor in ocular fluid of patients with diabetic
      retinopathy and other retinal disorders.
AB  - BACKGROUND: Retinal ischemia induces intraocular neovascularization, which often
      leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by
      stimulating the release of angiogenic molecules. Vascular endothelial growth
      factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production
      is increased by hypoxia. METHODS: We measured the concentration of VEGF in 210
      specimens of ocular fluid obtained from 164 patients undergoing intraocular
      surgery, using both radioimmuno-assays and radioreceptor assays. Vitreous
      proliferative potential was measured with in vitro assays of the growth of
      retinal endothelial cells and with VEGF-neutralizing antibody. RESULTS: VEGF was
      detected in 69 of 136 ocular-fluid samples from patients with diabetic
      retinopathy, 29 of 38 samples from patients with neovascularization of the iris,
      and 3 of 4 samples from patients with ischemic occlusion of the central retinal
      vein, as compared with 2 of 31 samples from patients with no neovascular
      disorders (P < 0.001, P < 0.001, and P = 0.006, respectively). The mean (+/- SD)
      VEGF concentration in 70 samples of ocular fluid from patients with active
      proliferative diabetic retinopathy (3.6 +/- 6.3 ng per milliliter) was higher
      than that in 25 samples from patients with nonproliferative diabetic retinopathy
      (0.1 +/- 0.1 ng per milliliter, P = 0.008), 41 samples from patients with
      quiescent proliferative diabetic retinopathy (0.2 +/- 0.6 ng per milliliter, P <
      0.001), or 31 samples from nondiabetic patients (0.1 +/- 0.2 ng per milliliter, P
      = 0.003). Concentrations of VEGF in vitreous fluid (8.8 +/- 9.9 ng per
      milliliter) were higher than those in aqueous fluid (5.6 +/- 8.6 ng per
      milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from
      the same patient; VEGF concentrations in vitreous fluid declined after successful
      laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells
      in vitro, as did vitreous fluid containing measurable VEGF. Stimulation was
      inhibited by VEGF-neutralizing antibodies. CONCLUSIONS: Our data suggest that
      VEGF plays a major part in mediating active intraocular neovascularization in
      patients with ischemic retinal diseases, such as diabetic retinopathy and retinal
      vein occlusion.

PMID- 7526214
TI  - The Brockenbrough-Braunwald-Morrow sign.

PMID- 7526216
TI  - Regulating physician-assisted death.

PMID- 7526215
TI  - Hepatitis C infection in patients with primary hypogammaglobulinemia after
      treatment with contaminated immune globulin.
AB  - BACKGROUND: In Scandinavia many patients with primary hypogammaglobulinemia
      contracted non-A, non-B hepatitis after intravenous treatment with an immune
      globulin product that was later found to contain a non-A, non-B hepatitis virus.
      METHODS: We studied the prevalence and clinical course of hepatitis C virus (HCV)
      infection in a group of 55 Norwegian patients with primary hypogammaglobulinemia
      and investigated its association with the use of contaminated immune globulin. We
      used the polymerase chain reaction to detect HCV RNA and performed HCV
      genotyping. We also analyzed the responses to treatment with interferon. RESULTS:
      Of 20 patients who received the contaminated immune globulin, 17 were
      seropositive for HCV RNA: In addition, 1 of 35 patients not exposed to the
      contaminated immune globulin was HCV RNA--positive. HCV genotype V was found in
      all 12 patients for whom genotyping was performed, but 8 patients also had
      genotype II or III, or both. All HCV RNA--positive patients had abnormal results
      on biochemical liver tests. All liver-biopsy specimens (from 15 patients) were
      abnormal, with portal inflammation, bile-duct damage, and focal necrosis. In six
      patients there was cirrhosis. Two patients died of liver failure. In 4 of the 10
      patients treated with interferon there were complete, though transient,
      biochemical responses, but the follow-up biopsy specimens showed evidence of
      histologic progression. The poorest responses to interferon were among the
      patients with multiple HCV genotypes. All but one patient remained positive for
      HCV RNA: CONCLUSIONS: In patients with primary hypogammaglobulinemia there was a
      high rate of HCV infection after treatment with contaminated immune globulin. In
      these immunocompromised patients HCV infection has a severe and rapidly
      progressive course, and responses to interferon are poor.

PMID- 7526217
TI  - Regulating physician-assisted death.

PMID- 7526218
TI  - Regulating physician-assisted death.

PMID- 7526219
TI  - Model for an RNA tertiary interaction from the structure of an intermolecular
      complex between a GAAA tetraloop and an RNA helix.
AB  - In large structured RNAs, RNA hairpins in which the strands of the duplex stem
      are connected by a tetraloop of the consensus sequence 5'-GNRA (where N is any
      nucleotide, and R is either G or A) are unusually frequent. In group I introns
      there is a covariation in sequence between nucleotides in the third and fourth
      positions of the loop with specific distant base pairs in putative RNA duplex
      stems: GNAA loops correlate with successive 5'-C-C.G-C base pairs in stems,
      whereas GNGA loops correlate with 5'-C-U.G-A. This has led to the suggestion that
      GNRA tetraloops may be involved in specific long-range tertiary interactions,
      with each A in position 3 or 4 of the loop interacting with a C-G base pair in
      the duplex, and G in position 3 interacting with a U-A base pair. This idea is
      supported experimentally for the GAAA loop of the P5b extension of the group I
      intron of Tetrahymena thermophila and the L9 GUGA terminal loop of the td intron
      of bacteriophage T4 (ref. 4). NMR has revealed the overall structure of the
      tetraloop for 12-nucleotide hairpins with GCAA and GAAA loops and models have
      been proposed for the interaction of GNRA tetraloops with base pairs in the minor
      groove of A-form RNA. Here we describe the crystal structure of an intermolecular
      complex between a GAAA tetraloop and an RNA helix. The interactions we observe
      correlate with the specificity of GNRA tetraloops inferred from phylogenetic
      studies, suggesting that this complex is a legitimate model for intramolecular
      tertiary interactions mediated by GNRA tetraloops in large structured RNAs.

PMID- 7526220
TI  - How did life begin. Guesswork and randomness (for now at least)

PMID- 7526221
TI  - The mechanics of life.

PMID- 7526222
TI  - Alternative pathway of insulin signalling in mice with targeted disruption of the
      IRS-1 gene.
AB  - The principal substrate for the insulin and insulin-like growth factor-1 (IGF-1)
      receptors is the cytoplasmic protein insulin-receptor substrate-1 (IRS-1/pp185).
      After tyrosine phosphorylation at several sites, IRS-1 binds to and activates
      phosphatidylinositol-3'-OH kinase (PI(3)K) and several other proteins containing
      SH2 (Src-homology 2) domains. To elucidate the role of IRS-1 in insulin/IGF-1
      action, we created IRS-1-deficient mice by targeted gene mutation. These mice had
      no IRS-1 and showed no evidence of IRS-1 phosphorylation or IRS-1-associated
      PI(3)K activity. They also had a 50 per cent reduction in intrauterine growth,
      impaired glucose tolerance, and a decrease in insulin/IGF-1-stimulated glucose
      uptake in vivo and in vitro. The residual insulin/IGF-1 action correlated with
      the appearance of a new tyrosine-phosphorylated protein (IRS-2) which binds to
      PI(3)K, but is slightly larger than and immunologically distinct from IRS-1. Our
      results provide evidence for IRS-1-dependent and IRS-1-independent pathways of
      insulin/IGF-1 signalling and for the existence of an alternative substrate of
      these receptor kinases.

PMID- 7526223
TI  - mRNAs can be stabilized by DEAD-box proteins.
AB  - Eubacterial messenger RNAs are synthesized and translated simultaneously;
      moreover the speed of ribosomes usually matches that of RNA polymerase. We report
      here that when in Escherichia coli the host RNA polymerase is replaced by the
      eightfold faster bacteriophage T7 enzyme for the transcription of the lacZ gene,
      the beta-galactosidase yield per transcript is depressed 100-fold. But the
      overexpression of DEAD-box proteins greatly improves this low yield by
      stabilizing the corresponding transcripts. More generally, it stabilizes
      inefficiently translated E. coli mRNAs. Ribosome-free mRNA regions, such as those
      lying behind the fast T7 enzyme or between successive ribosomes on inefficiently
      translated transcripts, are often unstable and we propose that DEAD-box proteins
      protect them from endonucleases. These results pinpoint the importance of
      transcription-translation synchronization for mRNA stability, and reveal an
      undocumented property of DEAD-box RNA helicases. These proteins have been
      implicated in a variety of processes involving RNA but not mRNA stability.

PMID- 7526224
TI  - Human immunodeficiency virus. Chaperoning a pathogen.

PMID- 7526225
TI  - Effects of saterinone and its enantiomers R(+)-saterinone and S(-)-saterinone on
      the phosphodiesterase isoenzymes from ventricular tissue of failing human hearts
      and porcine hearts.
AB  - Stereoisomers often exhibit differences in their pharmacological activities.
      Therefore, the phosphodiesterase inhibitory effects of the cardiotonic agent
      saterinone in form of the racemate were investigated in comparison with the
      inhibitory properties of its enantiomers R(+)- and S(-)-saterinone. For this
      purpose the phosphodiesterase isoenzymes from ventricular tissue of failing human
      hearts and porcine hearts were separated by DEAE-sepharose anion exchange
      chromatography. Four different phosphodiesterase isoenzymes were isolated from
      failing human myocardium and designated phosphodiesterase I-IV. Three
      phosphodiesterase isoenzymes could be separated from ventricular tissue of
      porcine hearts. A Ca2+/calmodulin stimulated phosphodiesterase I was not
      detectable in porcine myocardium. In failing human hearts racemic saterinone was
      a potent inhibitor of phosphodiesterase III (IC50 0.02 mumol/l) and IV (IC50 0.03
      mumol/l) as compared to the inhibition of phosphodiesterase I (IC50 37.3 mumol/l)
      and II (IC50 51.4 mumol/l). In comparison with the racemate, R(+)- and S(-)
      saterinone showed only slight differences in their phosphodiesterase inhibitory
      effects. R(+)-saterinone inhibited phosphodiesterase III slightly but
      significantly more potently and selectively than did S(-)-saterinone. Compared to
      the inhibition of phosphodiesterase I and II both enantiomers were similarly
      potent and selective inhibitors of phosphodiesterase III and IV. Similar results
      were obtained in porcine hearts. It is concluded that the racemate saterinone and
      its enantiomers (R(+)- and S(-)-saterinone are virtually equipotent concerning
      the inhibition of phosphodiesterase isoenzymes isolated from failing human hearts
      or porcine ventricular tissue. The enantiomers of saterinone did not exhibit
      distinct stereoselectivity in their phosphodiesterase inhibitory effects.

PMID- 7526226
TI  - [Presternal atheroma and its surgical treatment].

PMID- 7526227
TI  - Pretreatment with interleukin-1 enhances survival of sympathetic ganglionic
      neuron grafts.
AB  - The effects of pretreatment with interleukin-1 (IL-1) on neurite growth and cell
      survival of rat superior cervical ganglion (SCG) explants were examined. Neonate
      rat SCG explants were cultured with serum-containing growth media. Pretreatment
      with IL-1 beta (30 U/ml) for 3 hours stimulated neurite outgrowth of the SCG
      explant, which was inhibited by the addition of anti-nerve growth factor (NGF)
      antibody to the growth medium. Adult rat autologous SCG with the same
      pretreatment and non-treated ganglia were transplanted into the lateral
      ventricle. Histological evaluation of the grafts 2 weeks after transplantation
      revealed that the pretreated SCG cells survived better. Pretreatment with IL-1
      may achieve the NGF-mediated neurotrophic effect in sympathetic ganglionic
      neurons resulting in enhanced graft survival.

PMID- 7526228
TI  - Sequential changes in ischemic edema following transient focal cerebral ischemia
      in rats: magnetic resonance imaging study.
AB  - Sequential and regional changes in ischemic edema following various durations of
      focal cerebral ischemia were studied by magnetic resonance (MR) imaging in a rat
      unilateral intraluminal middle cerebral artery occlusion model. Occlusion was
      performed from 5 minutes to 5 hours. T2-weighted images were obtained
      chronologically 6 hours after onset of ischemia, on day 1 and day 7. An
      immunohistochemical study using antibodies to calcineurin and glial fibrillary
      acidic protein was performed to observe histological changes in the ischemic
      brain. The T2 high-signal-intensity areas representing ischemic edema were
      observed in the lateral striatum and/or the cerebral cortex by day 1 in all rats
      with 1- to 5-hour ischemia, and the areas were larger and detected earlier with
      longer durations of ischemia. In three of six rats with 15-minute ischemia and
      five of six rats with 30-minute ischemia, the T2 high-signal-intensity areas
      appeared transiently on day 1 in the dorsolateral striatum where loss of neurons
      expressing calcineurin immunoreactivity and associated gliosis were found. MR
      imaging in animal models of reversible focal ischemia can achieve sequential and
      noninvasive evaluation of dynamic regional changes in ischemic edema.

PMID- 7526229
TI  - Experimental study of the mechanism of seizure induction: changes in the
      concentrations of excitatory amino acids in the epileptic focus of the cat
      amygdaloid kindling model.
AB  - L-glutamate (Glu) and L-aspartate (Asp) are two major excitatory amino acids that
      may be involved in seizure susceptibility and seizure induction. The
      concentrations of Glu and Asp were measured by microdialysis in the epileptic
      focus in a cat amygdaloid kindling model. Sequential changes in Glu and Asp
      (before, during, and after seizure) were measured in the partial seizure (S4) and
      generalized seizure (S6) groups. By stimulation at and 50 microA below the
      partial seizure-triggering threshold in the S4 group and the generalized seizure
      triggering threshold in the S6 group, Glu was released from the epileptic focus
      in the S4 group, and both Glu and Asp were released in the S6 group after seizure
      and stimulation (below threshold), and the amount of Glu and/or Asp release
      determined seizure induction. Excitatory amino acids may be the trigger of
      seizure induction in the cat amygdaloid kindling model.

PMID- 7526230
TI  - Huge uncal branch of the anterior choroidal artery.
AB  - A huge uncal branch of the anterior choroidal artery was found in one of 22
      cerebral hemispheres. The uncal artery measured 0.7 mm in diameter. It gave off
      small branches to the uncus, as well as a large parahippocampal artery, the
      accessory anterior temporal artery, and the anterior hippocampal artery. This
      uncal artery supplied, in addition to the uncus, most of the ventromedial surface
      of the parahippocampal gyrus, part of its dorsal surface, the rostromedial
      portion of the lateral occipitotemporal gyrus, and the rostral part of the
      hippocampal formation. Such a huge uncal artery has implications for surgery in
      the uncohippocampal region.

PMID- 7526231
TI  - Lectin binding and bcl-2 protein expression in craniopharyngiomas.
AB  - The maturation process of basal cells in craniopharyngiomas was studied using a
      panel of lectins, and antibodies against cytokeratin 13 and bcl-2 protein, using
      oral mucosa for comparison. Seven lectins were employed: peanut (Arachis
      hypogaea) agglutinin, Dolichos biflorus agglutinin (DBA), Ulex europaeus
      agglutinin-I (UEA-I), soybean agglutinin, Ricinus communis agglutinin-I, succinyl
      wheat germ agglutinin, and Pisum sativum agglutinin. DBA and cytokeratin 13
      stainings of the suprabasal cells in craniopharyngiomas were comparable to those
      of the oral mucosa, but not to those of the skin. Staining patterns of the basal
      cells in the oral mucosa and craniopharyngiomas were generally similar, but UEA-I
      binding and bcl-2 protein expression in suprabasal cells differed. The difference
      appeared to be due to a disturbance in the differentiation of the basal cells,
      because only a small fraction of the basal cells followed a normal maturation
      process in craniopharyngiomas in comparison to the oral mucosa. The expression of
      bcl-2 protein may be involved in the pathogenesis of craniopharyngiomas.

PMID- 7526232
TI  - Magnetic resonance imaging and quantitative analysis of contents of epidermoid
      and dermoid cysts.
AB  - The intracapsular cholesterol, protein, and calcium contents of epidermoid and
      dermoid cysts from seven patients were compared with the signal intensities on T1
      weighted spin-echo magnetic resonance (MR) images. All specimens had a paste-like
      consistency when resected. Epidermoid and dermoid cysts demonstrated a wide range
      of cholesterol and calcium contents, and epidermoid cysts were not always rich in
      cholesterol. Five patients had cysts with lower signal intensity than white
      matter, which contained more than 18.3 mg/g wet weight of protein. One of these
      patients had the highest cholesterol content of all seven patients (22.25 mg/g
      wet weight) and another had the highest calcium content (0.75 mg/g wet weight).
      Two patients had cysts with higher signal intensity than white matter, with
      protein contents of lower than 4.3 mg/g wet weight. High protein content (> 18.3
      mg/g wet weight) may decrease signal intensity on T1-weighted MR images, while
      low protein content (< 4.3 mg/g wet weight) may increase signal intensity in
      epidermoid and dermoid cysts with high viscosity (paste-like consistency)
      contents.

PMID- 7526235
TI  - Magnetic resonance imaging of ecchordosis physaliphora--case report.
AB  - A rare case of ecchordosis physaliphora clearly demonstrated by magnetic
      resonance (MR) imaging is described in a 48-year-old male who presented with
      right hearing disturbance and reduction in sensation in the right side of his
      face due to a large cystic schwannoma. MR imaging revealed the large cystic
      schwannoma as well as an abnormal clival lesion. The clival lesion was
      hypointense on T1-weighted images and hyperintense on T2-weighted images, and not
      enhanced by gadolinium-diethylenetriamine-penta-acetic acid (Gd-DTPA)
      administration. The clival lesion was partially removed. The histological
      diagnosis was ecchordosis physaliphora. The postoperative course was uneventful.
      The absence of enhancement of ecchordosis physaliphora by Gd-DTPA administration
      may be a characteristic finding, in contrast to chordoma which is generally
      enhanced.

PMID- 7526233
TI  - Meningioma associated with intratumoral abscess formation--case report.
AB  - A rare case of meningioma associated with intratumoral abscess formation occurred
      in a 64-year-old female presenting with septic meningitis and a right frontal
      mass lesion after a gynecological operation under spinal anesthesia. The mass
      lesion was totally removed and revealed as an incidental meningioma with an
      intratumoral abscess. Hematogenous infection of Bacteroides oralis was thought to
      be the cause of the intratumoral abscess formation.

PMID- 7526236
TI  - Intracranial bullet retained since the Sino-Japanese war manifesting as
      hallucination--case report.
AB  - A 69-year-old male with an intracranial bullet retained in the right occipital
      lobe for 45 years presented with epileptic seizure occasionally accompanied by
      visual hallucinations. Neurological examination revealed left homonymous
      hemianopsia and right hearing loss, and electroencephalography showed slow
      discharges localized in the lesion. The bullet was removed together with the
      thickened fibrous capsule. His postoperative course was uneventful, and he has
      become seizure-free. The bullet caused metal toxicity and progressive gliosis,
      which caused the epileptogenetic focus and associated hallucinations.

PMID- 7526234
TI  - Diploic epidermoid tumor associated with subperiosteal hematoma--case report.
AB  - A 5-year-old boy presented with diploic epidermoid tumor associated with
      subperiosteal hematoma caused by minor trauma. The tumor was removed completely
      together with the hemorrhage. Bleeding from this type of tumor is unusual, but
      should be considered as an indication for surgical removal.

PMID- 7526237
TI  - Expression of nerve growth factor receptor by human primitive neuroectodermal
      tumors.
AB  - The expression of low-affinity nerve growth factor receptor (NGF-R) by primitive
      neuroectodermal tumors (PNETs) was analyzed in vivo and in vitro to investigate
      the relationship between NGF-R expression and cellular differentiation. NGF-R was
      expressed in one medulloblastoma cell line and two neuroblastoma cell lines. When
      these cells were induced to differentiate by treatment with dibutyryl cyclic
      adenosine monophosphate, NGF-R was overexpressed and there was increased
      expression of neurofilament proteins. Immunohistochemistry investigation of tumor
      tissues demonstrated that NGF-R was expressed by a subset of PNETs with a
      neuronal phenotype marked by neurofilament protein expression, but not by gliomas
      and PNETs without a neuronal phenotype. Growth inhibition assay demonstrated that
      NGF inhibited the growth of cells expressing NGF-R. These results indicate that
      NGF-R expression is a useful marker of neuronal differentiation by PNETs.

PMID- 7526239
TI  - Effect of radiosurgery using Leksell gamma unit on metastatic brain tumor-
      autopsy case report.
AB  - A 77-year-old male presented with gradual development of right hemiparesis.
      Postcontrast computed tomography (CT) revealed enhanced lesions in the left
      parietal and right paraventricular areas. Stereotactic brain biopsy led to a
      histological diagnosis of metastatic carcinoma. The lesions were treated by
      radiosurgery using the Leksell gamma unit. CT showed reduced size of the lesions
      after irradiation. The primary lesion could not be found and he died from
      pneumonia. Autopsy 3 weeks after the irradiation disclosed histological tumor
      necrosis, with greater tumor cell kill effects toward the center of the tumor.

PMID- 7526240
TI  - Suprasellar ectopic pituitary adenoma--case report.
AB  - A 33-year-old female presented with suprasellar ectopic pituitary adenoma
      manifesting as visual disturbances. Preoperative magnetic resonance imaging
      demonstrated intact pituitary gland and suprasellar cystic tumor, with a
      preoperative diagnosis of craniopharyngioma. At surgery, the tumor was identified
      as a suprasellar ectopic pituitary adenoma with intracapsular hematoma. There was
      no communication between the tumor and intrasellar structures. Total removal of
      the tumor immediately improved the severe visual disturbance. Ectopic pituitary
      adenoma should be considered in the differential diagnosis of a suprasellar
      lesion with intact pituitary gland.

PMID- 7526238
TI  - Lateral approach for anterior thoracic spinal lesions.
AB  - A lateral approach, consisting of a modified transversectomy, hemilaminectomy,
      and adequate transversectomy with costectomy of 7-8 cm, was used to treat four
      cases of anterior or anterolateral thoracic lesions, including two cases of
      thoracic disc herniations, one of thoracic meningioma, and one of hypertrophic
      pachymeningitis. All patients presented with gait disturbance, but recovered well
      postoperatively except for one who needed rehabilitation of the lower
      extremities. This approach provides a greater access to the anterior thoracic
      canal, and can achieve effective anterior decompression, and a good outcome for
      thoracic spinal disease if recognized early.

PMID- 7526241
TI  - Dural arteriovenous fistula caused by sinus thrombosis--case report.
AB  - A 58-year-old male with a history of idiopathic sinus thrombosis presented with
      gradual onset of gait disturbance, dementia, and involuntary movement in the
      upper extremities. Cerebral angiography demonstrated a dural arteriovenous
      fistula fed by a falx cerebelli branch originating from the left vertebral artery
      and draining into the inferior vermian vein, the straight sinus, a cortical vein
      lying on the inferolateral surface of the left cerebellar hemisphere, the
      ipsilateral superior petrosal sinus, the sigmoid sinus, and the internal jugular
      vein. Endovascular embolization under fluoroscopic control resulted in complete
      disappearance of the involuntary movement. Sinus thrombosis may result in
      development of dural arteriovenous fistula which can cause life-threatening
      complications, so aggressive therapy should be considered.

PMID- 7526242
TI  - Occlusion of internal carotid artery and formation of anterior communicating
      artery aneurysm in cervicocephalic fibromuscular dysplasia--follow-up case
      report.
AB  - A 44-year-old female with cervicocephalic-fibromuscular dysplasia (FMD) suffered
      a subarachnoid hemorrhage 10 years after presenting with left impaired
      extraocular movement. Carotid and vertebral angiography had shown string-of-beads
      sign in the left external carotid artery and fusiform aneurysms in the left
      carotid cavernous portion and in the left vertebral artery. On admission, the
      left carotid angiogram showed complete occlusion of the left internal carotid
      artery and the right carotid angiogram showed a new anterior communicating artery
      aneurysm. The territory of the left middle cerebral artery was supplied from the
      right internal carotid artery via the anterior communicating artery and from the
      basilar artery via the posterior communicating artery. Occlusion of the main
      arteries is rare in the clinical course of FMD. We suggest that hemodynamic
      stress due to occlusion of the internal carotid artery contributed to formation
      of the anterior communicating artery aneurysm, possibly associated with intrinsic
      changes of the arterial wall induced by FMD.

PMID- 7526243
TI  - Successful percutaneous transluminal angioplasty of the intracranial vertebral
      artery 1 month after total occlusion--case report.
AB  - A 51-year-old male suffering from recurrent cerebral ischemia due to total
      occlusion of the bilateral intracranial vertebral arteries more than 1 month old
      was successfully treated by percutaneous transluminal angioplasty (PTA). The
      totally occluded portion from the right intracranial vertebral artery to the
      basilar artery was adequately dilated. Follow-up angiography approximately 3
      months after angioplasty demonstrated no evidence of restenosis. His symptoms
      have not recurred. PTA is potentially a much less invasive and safer
      reconstruction than bypass surgery for total occlusions of the intracranial
      vertebral arteries less than 3 months old.

PMID- 7526244
TI  - Fenestration of the middle cerebral artery associated with an aneurysm--case
      report.
AB  - A 36-year-old female suddenly developed a severe headache. Computed tomography
      demonstrated subarachnoid hemorrhage in the left Sylvian fissure. Left carotid
      angiography revealed a fenestration at the distal portion of the M1 portion of
      the left middle cerebral artery, and an aneurysm arising from the proximal end of
      the fenestration. These findings were confirmed when the aneurysm neck was
      clipped. The embryonic origin of this lesion indicates that congenital factors
      may result in aneurysm formation.

PMID- 7526245
TI  - Solitary bone cyst of the cervical spine--case report.
AB  - A 63-year-old female presented with an extremely rare solitary bone cyst in the
      spine involving the C-5 vertebral body. Computed tomography showed an air-density
      area inside the cyst, without postcontrast enhancement. Magnetic resonance
      imaging demonstrated a low-intensity lesion on both T1- and T2-weighted images.
      At surgery, the cyst cavity contained no fluid. Histological examination of the
      surgical specimen revealed that the cyst wall was lined by a thin fibrous
      membrane. This rare bone cyst may have originated from a defect in the epiphyseal
      plate of the vertebral body.

PMID- 7526247
TI  - Immunohistochemical analysis of tumor-infiltrating lymphocytes and adhesion
      molecules (ICAM-1, NCAM) in human gliomas.
AB  - The presence of tumor-infiltrating lymphocytes (TILs) and the expression of
      adhesion molecules were examined in 12 glioma tissues. Most TILs were T
      lymphocytes, and both cytotoxic/suppressor and helper/inducer. T lymphocyte
      phenotypes were found. Neural cell adhesion molecule was intensely expressed in
      11 gliomas, and intercellular adhesion molecule-1 (ICAM-1) in seven. Many TILs
      were found only in gliomas expressing ICAM-1, but there was no relationship with
      clinical course in the patients.

PMID- 7526246
TI  - Hemimegaloencephaly with periventricular heterotopia--case report.
AB  - A 7-year-old girl was admitted with an unusual anomaly of hemimegaloencephaly
      associated with periventricular heterotopia manifesting as intractable seizures
      and mental retardation. Magnetic resonance (MR) imaging showed left hemispheric
      hypertrophy and left ventricular dilatation. Proton density-weighted MR imaging
      revealed a periventricular lesion isointense with gray matter. MR imaging is an
      effective method for diagnosing hemimegaloencephaly and heterotopia.

PMID- 7526248
TI  - Differentiation of malignant glioma and metastatic brain tumor by thallium-201
      single photon emission computed tomography.
AB  - The use of superdelayed thallium-201 single photon emission computed tomography
      (201Tl SPECT) for differentiating malignant gliomas from cerebral metastases was
      investigated in 23 patients (7 with meningioma, 6 with glioma, 7 with cerebral
      metastasis, 1 with each of neurinoma, abscess, and necrosis). 4 mCi of 201Tl was
      injected intravenously, and gamma camera scans were performed after 10 minutes
      and 4, 24, 72, and 96 hours (superdelayed scan). The mean thallium index of
      meningiomas was significantly higher than those of gliomas and cerebral
      metastases after 10 minutes, while the mean thallium indices of meningiomas and
      gliomas were significantly higher than those of cerebral metastases after 96
      hours. The combination of early and superdelayed 201Tl SPECT may be useful in
      differentiating malignant gliomas from cerebral metastases.

PMID- 7526249
TI  - Delayed cerebral ischemia manifesting as peduncular hallucinosis after aneurysmal
      subarachnoid hemorrhage--three case reports.
AB  - Three cases of peduncular hallucinosis occurred in patients with aneurysmal
      subarachnoid hemorrhage. All patients underwent early clipping of the ruptured
      aneurysms of the anterior circulation. Several days after onset of subarachnoid
      hemorrhage, the patients complained of vivid visual hallucinations associated
      with abnormal sleep-waking rhythms, suggesting a diagnosis of peduncular
      hallucinosis. The hallucinations disappeared with administration of an increased
      dose of dobutamine. These findings indicated that peduncular hallucinosis might
      be a manifestation of delayed cerebral ischemia after subarachnoid hemorrhage. No
      other possible cause of neurological deficits such as hydrocephalus, cerebral
      infarcts, or metabolic encephalopathies was identified. Damage to the ascending
      reticular activating system has been implicated in the pathogenesis of peduncular
      hallucinosis. Cerebral vasospasm in the perforating arteries of the ascending
      reticular activating system was probably the cause of the hallucinosis in our
      patients.

PMID- 7526250
TI  - Selection and combination of techniques for treating spontaneous carotid
      cavernous sinus fistulas.
AB  - Twenty-eight patients with spontaneous carotid-cavernous sinus fistulas (CCFs)
      were treated using a variety of techniques. Three of four patients with direct
      CCFs underwent intravascular embolization with a detachable balloon. Embolization
      with polyvinyl alcohol particles through an external carotid endoarterial route
      was used in six patients with indirect CCFs, and with ethylene-vinyl alcohol
      copolymer solution in two. Patients undergoing these conventional treatments,
      including embolization of the meningeal branches of the external carotid artery,
      had less satisfactory outcomes. The transvenous approach using minicoils through
      the inferior petrosal sinus was successful in eight patients. One patient treated
      using the transvenous approach using copper wire through the ophthalmic vein had
      worsening of visual acuity and field. Unsuccessful transvenous embolization in
      four patients required direct surgical exposure and embolization with spring
      coils. Spontaneous cures occurred in four patients. Direct CCFs with high flow
      rates were best treated with the detachable balloon or coil technique through a
      internal carotid endoarterial route. Indirect CCFs were best treated with the
      minicoil through the inferior petrosal sinus. If these techniques fail, direct
      surgical exposure allows placement of coils into the cavernous sinus.

PMID- 7526251
TI  - Early changes in volume and non-enhanced volume of acoustic neurinoma after
      stereotactic gamma-radiosurgery.
AB  - The effectiveness of stereotactic gamma-radiosurgery for treating acoustic
      neurinoma was evaluated by measuring the volumes of the tumor, non-enhanced
      tumor, and cerebellar edema in 13 patients with acoustic neurinoma who were
      followed up for 9 to 15 months (median 12.7 mos) after treatment. The tumor
      volume and non-enhanced volume tended to reach a maximum after 6 months, and
      cerebellar edema volume after 9 months, then decreased gradually thereafter.
      Hearing loss tended to increase gradually, but involvement of the facial nerve
      was transient.

PMID- 7526252
TI  - Cerebellar concussion--three case reports.
AB  - Three patients with transient cerebellar dysfunction following head injury are
      described. Acute cerebellar signs, such as ataxia, nystagmus, and dysarthria,
      occurred just after trauma and resolved gradually, disappearing in every patient.
      Cerebrospinal fluid and computed tomography examinations were normal but magnetic
      resonance imaging and single photon emission computed tomography revealed
      cerebellar lesions. These findings distinguish cerebellar concussion from
      cerebellar contusion and suggest that the synergistic effect of trauma and
      ischemia may be the pathophysiological basis of this unusual syndrome.

PMID- 7526253
TI  - Subarachnoidal abscess associated with bacterial meningitis in infants--two case
      reports.
AB  - Two infants, an 11-month-old boy and a 7-month-old girl, presented with
      subarachnoidal abscess associated with severe bacterial meningitis refractory to
      intensive managements with antibiotics. Computed tomography (CT) revealed
      bifrontal extracerebral low-density areas and remarkably enhanced surfaces of the
      bilateral frontal lobes postcontrast. Surgical exploration disclosed thick pus
      accumulation in the subarachnoid space which required curettage. The boy
      developed appropriately for his age, but the girl showed severe psychomotor
      retardation because of additional complications such as subdural fluid collection
      and hydrocephalus associated with the subarachnoidal abscess. Appropriate early
      neurosurgical management of subarachnoidal abscess is essential for satisfactory
      psychomotor development. Postcontrast CT should be performed to detect the
      subarachnoidal abscess as early as possible, and extensive craniotomy to remove
      the subarachnoidal pus accumulation performed to preserve psychomotor
      development.

PMID- 7526254
TI  - Vasculopathy of the anterior choroidal artery following intra-arterial
      chemotherapy--case report.
AB  - A 40-year-old male, treated with radiotherapy and supraophthalmic intracarotid
      artery (ICA) ACNU infusion for glioblastoma in the right occipital lobe,
      developed cerebral infarction secondary to vasculopathy manifesting as
      hemiparesis 3 months after a second ICA injection. The initial diagnosis was
      focal neurotoxicity, but angiography revealed severe vasospasm of the anterior
      choroidal artery. The symptoms improved gradually with therapy for the vasospasm.
      Angiography is required to discriminate vasospasm and focal neurotoxicity as a
      complication of ICA injection of antineoplastic agents.

PMID- 7526255
TI  - Posterolateral extradural approach for lateral thoracic meningocele--case report.
AB  - A 26-year-old female presented with a lateral thoracic meningocele associated
      with neurofibromatosis. The development of the thoracic meningocele was
      documented on serial chest roentgenograms. Magnetic resonance imaging and three
      dimensional bone computed tomography scans were particularly useful to identify
      organic changes in the surrounding structures and the osseous orifice of the
      dural sac, respectively. The large thoracic meningocele was successfully treated
      through the posterolateral extradural approach in combination with resection of
      the adjacent ribs and cerebrospinal fluid drainage from the dural sac.

PMID- 7526256
TI  - Primary Ewing's sarcoma of the skull base with intracerebral extension--case
      report.
AB  - A 32-year-old female presented with an uncommon primary Ewing's sarcoma of the
      skull involving the middle cranial fossa with an extremely unusual extension into
      the cerebral parenchyma. She was treated with surgical excision, irradiation, and
      chemotherapy. Two years after surgery she demonstrated no evidence of local
      recurrence or distant metastasis. Ewing's sarcoma of the skull may achieve a
      better survival rate under adequate management than this lesion in other sites.

PMID- 7526258
TI  - Neurodevelopmental outcome at 5-7 years in preterm infants with periventricular
      leukomalacia.
AB  - We describe outcome at 5-7 years of 37 subjects with periventricular leukomalacia
      (PVL). Children were divided into 3 groups based on PVL type and clinical
      outcome. Subjects with cystic PVL > or = 5 mm-1 cm or more (n = 14) all developed
      CP. CP was found in only 2 subjects out of 11 with cystic PVL < 5 mm. One had GII
      < 70 according to McCarthy's Scales of Children's abilities. Mild neurological
      signs were present in 7 and 1 child was normal. Subjects with so-called
      "prolonged flare" (n = 12) included 6 CP cases, 4 with mild neurological signs
      and 2 normal subjects. Prognosis was related to site and number of cysts.
      Cognitive profiles tended to be disharmonic, with discrepancies between verbal,
      performance and motor scores. We conclude that PVL represents an important
      diagnostic tool in both short and long-term neurodevelopmental outcome.

PMID- 7526257
TI  - Prolactin and growth hormone release and calcium influx are stimulated by galanin
      within a 'window' range of concentrations in pituitary GH3 B6 cells.
AB  - Galanin is widely distributed throughout the rat neural and endocrine system with
      the highest concentration in the anterior pituitary. The effects of galanin were
      investigated in rat tumor pituitary cells (GH3/B6). A single stimulation with
      galanin caused prolactin (PRL) and growth hormone (GH) release within a narrow
      range of concentrations (10(-11)-10(-9) M). However, secretory responses were not
      consistently observed upon subsequent galanin stimulation. Galanin triggered a
      rise in cytosolic Ca2+ (burst in [Ca2+]i transients) with a similar
      responsiveness. By contrast, no change in PRL mRNA was detectable in response to
      the peptide. These data suggest that galanin which binds to high-affinity
      receptors in anterior pituitary cells can exert subtle modulations of pituitary
      cell functions.

PMID- 7526259
TI  - Modulation by alkyl p-hydroxybenzoates of voltage- and ligand-gated channels in
      peripheral neuronal cells.
AB  - Effects of alkyl p-hydroxybenzoates (APHBs), which are used as preservatives, on
      ion channels were investigated in rat pheochromocytoma PC12 cells. Methyl p
      hydroxybenzoate (MPHB; 300 microM) and butyl p-hydroxybenzoate (BPHB; 300 microM)
      inhibited Ba2+ current passing through Ca2+ channels, and facilitated the
      inactivation of the Ba2+ current. K+ current obtained with a depolarizing voltage
      step was also suppressed by 300 microM MPHB or 300 microM BPHB. The extent of the
      suppression of the K+ current was not affected by extracellular Cd2+, suggesting
      that the suppression of the K+ current is not a secondary effect arising from the
      Ca2+ channel inhibition. An inward current activated by acetylcholine (ACh; 100
      microM) was abolished by 300 microM BPHB, and it was partially blocked by 300
      microM MPHB. In contrast to the ACh-activated current, an inward current
      activated by ATP (30 microM) was markedly potentiated by 300 microM BPHB. The
      results suggest that APHBs exert significant effects on the voltage- and ligand
      gated channels. The significance of these channel modifications were discussed in
      relation to reported effects of APHBs, including induction of minor irritation.

PMID- 7526260
TI  - Synthesis and biological activity of NK1 substance P selective agonists by
      modifying the methionyl residue.
AB  - A series of analogues of substance P, where the Met11 residue was replaced by
      Glu(OCH2CH3), Glu(OBzl) and Hse(CH3), were synthesized in order to investigate
      the effect on agonist activity of modifications at the C-terminal residue. The
      biological activities in the guinea-pig ileum assay (NK1 receptor) and rat [text
      says rabbit] pulmonary artery (NK2 receptor) indicate that replacement of the
      SCH3 group of Met11 of substance P by the COOBzl or OCH3 groups favour
      interaction with the NK1 receptor and increase selectivity towards this receptor
      subtype.

PMID- 7526262
TI  - Effect of mild hypothermia on nitric oxide synthesis during focal cerebral
      ischemia.
AB  - The cerebroprotective effects of mild hypothermia have been extensively studied
      in various animal models of ischemia, but the mechanism by which mild hypothermia
      diminishes ischemic injury is not well understood. Nitric oxide (NO) has been
      implicated as a mediator of glutamate excitotoxicity in primary neuronal
      cultures, and its synthesis is acutely increased during focal ischemia in vivo.
      To evaluate possible mechanisms of hypothermic neuroprotection, we measured
      markers of NO synthesis--nitrite and cyclic guanosine monophosphate (cGMP) levels
      and NO synthase activity--during right middle cerebral artery occlusion (MCAO) in
      the rat under normothermic (36.5 degrees C) and mild hypothermic (33 degrees C)
      conditions. There was a significant increase in nitrite concentration in the
      right hemisphere versus the left under normothermic conditions at 10 and 20
      minutes after MCAO (P < 0.01), with a return to baseline levels by 60 minutes.
      The increase in cortical nitrite levels in the right hemisphere versus the left
      was not observed with mild hypothermia. There was a threefold increase in cGMP
      synthesis in the normothermic right cortex 10 minutes after MCAO (P < 0.05). This
      rise in cGMP did not occur in hypothermic animals, and the right to left cortical
      disparity in cGMP production was abolished. Finally, the significant increase in
      NO synthase activity seen in the normothermic ischemic cortex was absent in
      hypothermic rats (P < 0.05). These results suggest that mild hypothermia (33
      degrees C) modulates the burst of nitric oxide synthesis during cerebral ischemia
      and may account, at least partially, for its cerebroprotective effects.

PMID- 7526261
TI  - Skeletal muscle microcirculatory response to rat alpha-calcitonin gene-related
      peptide.
AB  - We used in vivo video microscopy to determine the effect of increasing doses of
      rat alpha-calcitonin gene-related peptide (rCGRP) on rat cremaster muscle
      arterioles in the presence or absence of the nitric oxide synthase inhibitor N
      omega-nitro-L-arginine (L-NNA). Male Sprague-Dawley rats (118-148 g) were
      anaesthetized with pentobarbital, and neurovascularly intact cremaster muscles
      were imaged. Changes in the diameter, erythrocyte velocity and volume flow in
      second-(A2), third-(A3), and fourth-(A4) order arterioles were determined. To
      produce uniform arteriolar tone, the cremaster preparation was challenged with
      norepinephrine (NE: 10(-7) M). L-NNA (10(-4) M), which was shown to inhibit
      acetylcholine-(ACh: 10(-6) M) induced arteriolar dilations, was added to 16 of
      the preparations. Preparations were then challenged by adding cumulative log
      concentrations of rCGRP (10(-12)-10-7) M; n = 16) or an equivalent volume of
      vehicle (n = 19) to the bath. Following rCGRP challenge, arterioles were
      maximally dilated with 10(-5) M nitroprusside (NP). rCGRP caused significant dose
      dependent increases in erythrocyte velocity and volume flow in A2 arterioles, and
      in diameter, velocity, and volume flow in A3 and A4 arterioles, by 10(-8) M, when
      compared with vehicle-treated controls. L-NNA had no significant effect on rCGRP
      induced responses. These data indicate that rCGRP causes dose-dependent dilation
      of skeletal muscle resistance arterioles at a concentration similar to that
      observed in larger vessels. This dilation does not appear to be dependent on the
      vascular production of nitric oxide from L-arginine.

PMID- 7526263
TI  - The limited value of cytoreductive surgery in elderly patients with malignant
      gliomas.

PMID- 7526264
TI  - Failure to prevent selective CA1 neuronal death and reduce cortical infarction
      following cerebral ischemia with inhibition of nitric oxide synthase.
AB  - We investigated the putative role of nitric oxide in the expression of neuronal
      injury following both transient severe forebrain ischemia (CA1 neuronal injury)
      and transient or permanent middle cerebral artery occlusion (neocortical
      pannecrosis). Using the four-vessel occlusion model and increasing doses of N
      omega-nitro-L-arginine, 2-40 mg/kg, we were unable to demonstrate any reduction
      in the percentage of CA1 cells injured following 10 min of transient severe
      forebrain ischemia followed by seven days of reperfusion. Higher doses proved
      toxic insofar as they increased the mortality following the ischemic insult.
      Saline-treated animals (n = 8) had 77 +/- 10% CA1 injury while those treated with
      2 mg/kg of nitro-arginine i.v. had 80 +/- 7% (n = 7), and those with 10 mg/kg
      i.v. had 78 +/- 11% (n = 8). Two of five rats given 20 mg/kg i.v., three of eight
      given 40 mg/kg i.v., and two of six given 10 mg/kg i.v. followed by 3 x 10 mg/kg
      i.p., died. Of those treated with high-dose nitro-arginine and which survived
      ischemia and seven days' reperfusion, no significant reduction in CA1 injury was
      detected. Wistar rats and spontaneously hypertensive rats treated with either
      saline or nitro-arginine i.v. were exposed to 2 h of transient middle cerebral
      artery occlusion followed by 22 h of reperfusion. There were seven animals in
      each group. Wistars treated with saline had 198 +/- 67 mm3 (mean +/- S.D.) of
      neocortical infarction, and those treated with 10 m/kg of nitro-arginine i.v. had
      199 +/- 93 mm3. Spontaneously hypertensive rats, transiently ischemic, treated
      with saline had 164 +/- 25 mm3 of infarct volume, while those treated with 2
      mg/kg i.v. had 151 +/- 53 mm3, and those treated with 10 mg/kg i.v. had 145 +/-
      29 mm3. Animals treated with 40 mg/kg i.v. had a nonsignificantly larger mean
      infarct volume (191 +/- 81 mm3). High dose nitro-arginine caused an increase in
      hypertension in the spontaneously hypertensive rats and increased the severity of
      focal ischemia as measured by intra-ischemic regional cerebral blood flows. A
      final group of seven spontaneously hypertensive rats underwent permanent middle
      cerebral artery occlusion and repeated dosing with N-omega-nitro-L-arginine i.p.
      In these animals an infarct volume of 234 +/- 60 mm3 was observed, which was
      again not statistically different from saline-treated controls (208 +/- 43 mm3, n
      = 7).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7526265
TI  - Subpopulations of GABAergic neurons in laminae I-III of rat spinal dorsal horn
      defined by coexistence with classical transmitters, peptides, nitric oxide
      synthase or parvalbumin.
AB  - GABAergic neurons in laminae I-III of the spinal dorsal horn may contain one or
      more of the following compounds: glycine, acetylcholine, neuropeptide Y,
      enkephalin, nitric oxide synthase or parvalbumin. Although the pattern of co
      localization of some of these compounds is understood, it is not known which
      types of GABAergic neurons contain parvalbumin, or whether nitric oxide synthase
      coexists with peptides, acetylcholine or parvalbumin in any of these neurons, and
      in this study we have used immunocytochemistry and enzyme histochemistry to
      resolve these issues. Parvalbumin-immunoreactivity was restricted to those GABA
      immunoreactive neurons that also showed glycine-immunoreactivity and was not co
      localized with neuropeptide Y-immunoreactivity or NADPH diaphorase activity. By
      combining NADPH diaphorase histochemistry with immunocytochemistry with an
      antiserum to nitric oxide synthase, we were able to show that NADPH diaphorase
      activity was a reliable marker for nitric oxide synthase in the spinal cord.
      Neurons that possess GABA- but not glycine-immunoreactivity may contain
      neuropeptide Y, enkephalin, acetylcholine or NADPH diaphorase, and all of the
      cholinergic neurons appear to contain NADPH diaphorase. By combining
      immunofluorescent detection of neuropeptide Y or enkephalin with NADPH diaphorase
      histochemistry, we showed that peptide-immunoreactivity did not coexist with
      NADPH diaphorase. This suggests that neither of these peptides coexists with
      nitric oxide synthase or with acetylcholine in neurons in the superficial dorsal
      horn. Several phenotypically distinct groups of GABA-immunoreactive neuron can
      therefore be identified in laminae I-III of the dorsal horn, and these may
      represent different functional types of inhibitory neuron.

PMID- 7526266
TI  - Mechanism of alpha-latrotoxin action as revealed by patch-clamp experiments on
      Xenopus oocytes injected with rat brain messenger RNA.
AB  - Single-channel currents produced by alpha-latrotoxin from the black widow spider
      venom were recorded on Xenopus oocytes injected with rat brain messenger RNA
      fraction of 7-8 kb. Single-channel conductance varied from 3 pS to 200 pS and
      sublevels of similar conductance were observed at both normal and high external
      concentration of Ca2+. Currents reversed at 0 mV, and the channels were permeable
      to Ca2+, Na+ and K+ indicating non-selective cation channel produced by the
      toxin. Ca2+ stabilized the channel mainly at one conducting sublevel. Studies of
      channel kinetics indicated that openings co-operated into groups of bursts.
      Within these groups the histograms of closed and open times showed two
      exponentials with mean times near 1.5 ms and 20 ms for the closed time histogram
      and 85 ms and 300 ms for the open time histogram at -40 mV. Open times increased
      with membrane hyperpolarization while closed times did not. Open probability was
      near 0.8 and slightly increased with hyperpolarization. Elevation of external
      Ca2+ or toxin concentration promoted the appearance of groups of burst openings
      while within these groups, the single-channel conductance, the reversal potential
      and channel kinetics did not depend on Ca2+ or toxin concentration. On the basis
      of the experimental results, the kinetic mechanism of toxin action has been
      proposed. The data strongly suggest that alpha-latrotoxin molecules are cation
      channels associated into clusters that insert into the membrane after binding to
      the receptor located at active zones of synaptic transmission. Binding and
      synchronization of channel openings in a cluster are promoted by Ca2+. Influx of
      Ca2+ through this near permanently open cation channel seems to induce intensive
      synaptic vesicle fusion and massive neurotransmitter release.

PMID- 7526267
TI  - Projections of the suprachiasmatic nuclei, subparaventricular zone and
      retrochiasmatic area in the golden hamster.
AB  - The patterns of projections from the hamster suprachiasmatic nucleus,
      retrochiasmatic area and subpraventricular hypothalamic zone were examined using
      anterograde tracing with the plant lectin, Phaseolus vulgaris leucoagglutinin.
      Suprachiasmatic nucleus efferents comprise four major fiber groups: (i) an
      anterior projection to the ventral lateral septum, the bed nucleus of the stria
      terminalis and anterior paraventricular thalmus; (ii) a periventricular
      hypothalamic projection extending from the preoptic region to the premammillary
      area; (iii) a lateral thalamic projection to the intergeniculate leaflet and
      ventral lateral geniculate; and (iv) a posterior projection to the posterior
      paraventricular thalamus, precommissural nucleus and olivary pretectal nucleus.
      The retrochiasmatic area showed a similar projection pattern with several major
      exceptions. There are projections to endopiriform cortex, fundus striati, ventral
      pallidum, horizontal limb of the nucleus of the diagonal band and three separate
      routes to the amygdala. There are also projections laterally with fibers of the
      supraoptic commissures, which enter the superior thalamic radiation and innervate
      the caudal dorsomedial thalamic nuclei. Other fibers traveling with the
      commissures terminate in the ventral zona incerta. The subparaventricular zone
      projects to most targets of the suprachiasmatic nucleus, but not to the
      intergeniculate leaflet. There is a substantial input to both the
      subparaventricular zone and retrochiasmatic area from the suprachiasmatic
      nucleus, but little apparent reciprocity. There is extensive overlap of
      suprachiasmatic nuclei and retrochiasmatic efferents, and between retrochiasmatic
      and known medial amygdaloid efferents. The anatomical information is discussed in
      the context of circadian rhythm regulation, photoperiodism and chemosensory
      pathways controlling male hamster reproductive behavior.

PMID- 7526268
TI  - Involvement of retinohypothalamic input, suprachiasmatic nucleus, magnocellular
      nucleus and locus coeruleus in control of melanotrope cells of Xenopus laevis: a
      retrograde and anterograde tracing study.
AB  - The amphibian Xenopus laevis is able to adapt the colour of its skin to the light
      intensity of the background, by releasing alpha-melanophore-stimulating hormone
      from the pars intermedia of the hypophysis. In this control various inhibitory
      (dopamine, gamma-aminobutyric acid, neuropeptide Y, noradrenaline) and
      stimulatory (thyrotropin-releasing hormone and corticotropin-releasing hormone)
      neural factors are involved. Dopamine, gamma-aminobutyric acid and neuropeptide Y
      are present in suprachiasmatic neurons and co-exist in synaptic contacts on the
      melanotrope cells in the pars intermedia, whereas noradrenaline occurs in the
      locus coeruleus and noradrenaline-containing fibres innervate the pars
      intermedia. Thyrotropin-releasing hormone and corticotropin-releasing hormone
      occur in axon terminals in the pars nervosa. In the present study, the neuronal
      origins of these factors have been identified using axonal tract tracing.
      Application of the tracers 1,1'dioctadecyl-3,3,3',3' tetramethyl indocarbocyanine
      and horseradish peroxidase into the pars intermedia resulted in labelled neurons
      in two brain areas, which were immunocytochemically identified as the
      suprachiasmatic nucleus and the locus coeruleus, indicating that these areas are
      involved in neural inhibition of the melanotrope cells. Thyrotropin-releasing
      hormone and corticotropin-releasing hormone were demonstrated
      immunocytochemically in the magnocellular nucleus. This area appeared to be
      labelled upon tracer application into the pars nervosa. This finding is in line
      with the idea that corticotropin-releasing hormone and thyrotropin-releasing
      hormone stimulate melanotrope cell activity after diffusion from the neural lobe
      to the pars intermedia. After anterograde filling of the optic nerve with
      horseradish peroxidase, labelled axons were traced up to the suprachiasmatic area
      where they showed to be in contact with suprachiasmatic neurons. These neurons
      showed a positive reaction with anti-neuropeptide Y and the same held for
      staining with anti-tyrosine hydroxylase. It is suggested that a retino
      suprachiasmatic pathway is involved in the control of the melanotrope cells
      during the process of background adaptation.

PMID- 7526269
TI  - Indirect nucleus accumbens input to the prefrontal cortex via the substantia
      nigra pars reticulata: a combined anatomical and electrophysiological study in
      the rat.
AB  - The nucleus accumbens is a major component of the ventral striatum through which
      most of the limbic affiliated cortical areas gain access to the basal ganglia
      circuitry. In this study, the organization of the pathways linking the nucleus
      accumbens to the thalamus, via the substantia nigra pars reticulata, was examined
      in the rat using anatomical and electrophysiological methods. Use of anterograde
      and retrograde transport of wheatgerm agglutinin conjugated to horseradish
      peroxidase has established that the core of the nucleus accumbens innervates a
      dorsal region of the substantia nigra pars reticulata which projects to subfields
      of the mediodorsal and ventral medial thalamic nuclei. These subfields consist of
      the rostral pole of the mediodorsal nucleus with the exception of its central
      segment and a region of the ventral medial nucleus, medial to the
      mammillothalamic tract. Confirming the existence of a nucleus accumbens
      nigrothalamic link, we have observed that electrical or chemical stimulation of
      the nucleus accumbens induces an inhibition of the spontaneous discharges of the
      nigral cells which project to the mediodorsal and ventral medial thalamic nuclei.
      Finally, the cortical projections of the thalamic subfields involved in the
      nucleus accumbens nigrothalamic circuit were determined using the anterograde and
      retrograde axonal transport of wheatgerm agglutinin conjugated with horseradish
      peroxidase. These subfields innervate mainly the prelimbic and to a lesser degree
      the orbital areas of the prefrontal cortex. The present data show that the
      substantia nigra pars reticulata is a major link between the core of the nucleus
      accumbens and the prefrontal cortex and provide further evidence for the concept
      of a parallel architecture in the basal ganglia thalamocortical circuits of the
      ventral striatum.

PMID- 7526270
TI  - NADPH-diaphorase in the spinal trigeminal nucleus oralis and rostral solitary
      tract nucleus of rats.
AB  - NADPH-diaphorase histochemical staining demonstrated a distinct neural group that
      might synthesize nitric oxide in the lower brainstem of rats. The NADPH
      diaphorase stain revealed a Golgi-like network in the dorsomedial spinal
      trigeminal nucleus oralis and rostrolateral solitary tract nucleus, whereas this
      network was more dense in the latter nucleus. The distribution of NADPH
      diaphorase-positive neurons in these areas overlapped with parts of central
      terminations from the chorda tympani nerve, as demonstrated with transganglionic
      transport of wheatgerm agglutinin conjugated horseradish peroxidase. The number
      of NADPH-diaphorase-positive neurons changed after chorda tympani nerve lesion
      relative to the contralateral side. The control value (%) was 106.0 +/- 4.9 (mean
      +/- S.E.M.). One hour after the nerve lesion, the value increased to 115.2 +/-
      9.1 (P > 0.05). It then decreased to 83.9 +/- 5.2 two days after the lesion (P <
      0.05), and remained at this reduced level for one or two weeks, 83.2 +/- 3.0 (P <
      0.01) and 83.7 +/- 2.3 (P < 0.01), respectively. This statistically significant
      reduction recovered to control level 103.4 +/- 2.9 four weeks after the lesion.
      These results show that NADPH-diaphorase-positive neurons in the lower brainstem
      could be regulated trans-synaptically by primary afferents, possibly gustatory
      inputs.

PMID- 7526272
TI  - Anatomy and physiology of glutamate in the CNS.
AB  - Glutamate is the predominant excitatory neurotransmitter in the mammalian CNS.
      The neurotransmitter pool of glutamate is stored in synaptic vesicles and, upon
      depolarization, is released into the synaptic cleft in a Ca(2+)-dependent
      fashion. Glutamate is cleared from the synaptic cleft by high-affinity, Na(+)
      dependent uptake carriers located in both neurons and glia. Glutamate acts on
      several distinct families of receptors, each of which has multiple subtypes with
      distinct pharmacologic and physiologic properties. Under some conditions,
      glutamate and related compounds act as excitotoxins and might participate in the
      events leading to neuronal damage and death in a variety of acute and chronic
      neurologic disorders. The potential for glutamate to become an excitotoxin is
      highly dependent upon neuronal metabolic status. A great deal of interest in
      developing selective, well-tolerated glutamate receptor antagonists for the
      treatment of a variety of neurologic disorders exists.

PMID- 7526271
TI  - Localization of age-related changes in NADPH-diaphorase activity in pancreatic
      neurons.
AB  - The distribution of NADPH-diaphorase activity in the pancreatic neurons of
      neonatal, adult and aging rats was investigated using histochemistry. In the
      neonates, only 40% of the neuronal population showed NADPH-diaphorase labelling,
      and there was variation in the intensity of labelling ranging from light to heavy
      staining. In the young and mature adults, 95% of the neurons were labelled for
      NADPH-diaphorase activity, with most of the neurons being heavily labelled for
      the enzyme in the older animals. Immediately after birth, the pancreatic neurons
      found were small clusters of smaller sized cells compared with those observed in
      the mature adults. Their number reached the adult level by the third month after
      birth; this was maintained throughout the mature adult phase and subsequently
      decreased in the aging rats.

PMID- 7526273
TI  - Changed excretion of urinary proteins and enzymes by chronic exposure to lead.
AB  - Fifteen various serum and urine parameters were evaluated as indicators of renal
      alterations induced by lead in 82 male workers of a battery plant chronically
      exposed to lead (median of blood lead concentration: 2.03 mumol/l). The control
      group comprised 44 non-exposed healthy volunteers (0.34 mumol/l). High-molecular
      mass proteins (transferrin, immunoglobulin G (IgG), (albumin)) were determined in
      urine as markers of glomerular integrity; low-molecular-weight proteins and
      parenchymal enzymes (alpha 1-microglobulin, beta 2-microglobulin, retinol-binding
      protein, lysozyme, ribonuclease, N-acetyl-beta-D-glucosaminidase (NAG), alanine
      aminopeptidase (AAP), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT))
      as indicators of changes in the proximal tubule; Tamm-Horsfall glycoprotein and
      kallikrein as markers of the distal tubule. There was a positive correlation
      between tubular indicators and blood lead concentration as well as the
      erythrocyte protoporphyrin (EPP). About 30% of the lead-exposed workers showed an
      increased excretion of alpha 1-microglobulin, NAG, ribonuclease, and/or Tamm
      Horsfall protein, whereas the glomerular indicators remained unchanged. The
      combined determination of NAG and alpha 1-microglobulin in urine could be helpful
      in the early detection of lead-induced changes in the nephron.

PMID- 7526274
TI  - Circulating soluble adhesion molecules in systemic vasculitis.
AB  - The plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), E
      selectin (sE-selectin), and vascular cell adhesion molecule-1 (sVCAM-1), might
      reflect endothelial activation and injury and would therefore be useful markers
      of disease activity in vasculitis. To investigate this we measured the levels of
      sICAM-1, sE-selectin, and sVCAM-1 by two-site ELISAs in the plasma of patients
      with (a) active vasculitis (n = 16), (b) vasculitis in remission (n = 15), (c)
      chronic renal failure (CRF) (n = 10), and (d) normal healthy controls (n = 10).
      Plasma sICAM-1 levels were significantly higher in patients with active
      vasculitis, 323 ng/ml (193-607) compared with patients with inactive vasculitis,
      199 ng/ml (131-297); P = 0.0006 and healthy controls, 188 ng/ml (138-259); P =
      0.0002. Plasma sE-selectin levels were also significantly higher in the patients
      with active vasculitis, 45 ng/ml (15-65) compared with patients with inactive
      vasculitis, 25 ng/ml (15-55); P = 0.027 but not when compared with healthy
      controls, 35 ng/ml (20-55); P = 0.16. There was no difference in plasma sVCAM-1
      levels between patients with active vasculitis, OD 0.56 (0.45-0.85) and inactive
      disease, OD 0.58 (0.47-0.79) (P = 0.12) or with healthy controls OD 0.49 (0.42
      0.68) (P = 0.48). There were no significant differences between the plasma levels
      of any of the soluble adhesion molecules between patients with active vasculitis
      and patients with chronic failure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526276
TI  - Tryptophan and its metabolites in patients on continuous ambulatory peritoneal
      dialysis and following renal transplantation.
AB  - Plasma tryptophan (Trp) concentration in its total (TTrp) and non-protein-bound
      free form (FTrp) and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) as
      well as muscle Trp contents (MTrp) were studied in 12 uraemic patients undergoing
      continuous ambulatory peritoneal dialysis (CAPD), 10 renal transplant patients,
      and 10 healthy control subjects. The CAPD patients exhibited signs of muscle
      weakness, as assessed by dynamometry, and signs of protein malnutrition with a
      decreased ratio of alkali-soluble protein relative to DNA in muscle as well as
      low serum albumin concentration. In the uraemic patients TTrp was markedly
      reduced, whereas in the transplant patients it did not differ from the controls.
      The FTrp, which was separated by the process of equilibrium dialysis, was less in
      the uraemic (P < 0.01) as well as transplant patients (P < 0.01) than in the
      controls. The plasma FTrp/TTrp ratio was increased in the uraemic patients (40 +/
      8%) but less in the transplant patients (16 +/- 4%), as compared to the controls
      (25 +/- 5%). The uraemic patients had increased plasma concentrations of 5-HIAA,
      whereas this metabolite could not be found in the plasma of renal transplant
      patients and healthy controls. MTrp was increased by an average of 33% in the
      uraemic patients whereas it did not differ between the transplant patients and
      the controls. The results indicate that the abnormal Trp metabolism in uraemic
      patients is to a large extent corrected by a successful renal
      transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526275
TI  - Antibodies to hepatitis C virus (HCV) in chronic renal failure (CRF) patients on
      conservative therapy: prevalence, risk factors and relationship to liver disease.
AB  - There are no data regarding HCV prevalence in CRF patients not requiring
      dialysis. In order to assess prevalence and risk factors for HCV infection in CRF
      patients on conservative therapy we tested, by second-generation assays such as
      Ortho 2 and 4-RIBA, 221 predialysis CRF patients attending our Department. Forty
      four (20%) patients were anti-HCV positive. Anti-HCV positivity was related to
      blood transfusion requirement, past or current elevations of transaminase levels
      and, to a lesser degree, CRF duration. The prevalence of anti-HCV positivity
      among CRF patients who were never transfused was about 10 times higher than that
      of blood donors. Our data show that predialysis CRF patients should be considered
      a specific risk group for HCV infection; blood transfusion history and duration
      of CRF are risk factors for acquisition of HCV infection; HCV infection may play
      a role in the development of liver disease in this clinical setting.

PMID- 7526278
TI  - Renal arteriopathy associated with FK 506 therapy following liver
      transplantation.

PMID- 7526277
TI  - Effectiveness of adenine arabinoside 5'-monophosphate in kidney transplant
      recipients with chronic active hepatitis B.
AB  - Hepatitis B virus infection is responsible for both morbidity and mortality in
      kidney transplant recipients. Adenine arabinoside 5'-monophosphate (ARA-AMP), a
      synthetic purine nucleotide with anti-viral activity, leads to a sustained
      interruption of HBV replication in approximately 40% of immunocompetent patients.
      We report the results of a pilot study using ARA-AMP to treat HBV-related chronic
      active hepatitis in kidney transplant recipients. Ten patients (2 females and 8
      males, mean age 44 years, mean time post-transplantation 163 months) received a
      28-day course of ARA-AMP intramuscularly: 5 mg/kg twice daily for the first 5
      days during hospitalization and subsequently 5 mg/kg once daily at home for the
      remaining 23 days. Mean follow-up was 18 months, ranging from 7 to 28 months. All
      patients but one had biopsy-proven chronic hepatitis, including five cases of
      cirrhosis. All patients had been chronic HBs Ag carriers for more than 1 year and
      had active replication as assessed by the presence of serum HBV DNA (mean titre,
      270 pg/ml, ranging from 12 to 997 pg/ml, Genostics method). HBe Ag was present in
      7 of the 10 patients. Pretreatment creatinine was normal. In four of the 10
      patients, HBV DNA became undetectable respectively 1, 1, 5, and 11 months after
      beginning ARA-AMP. In five patients, HBV DNA decreased during ARA-AMP therapy but
      subsequently increased although no change was noted during the follow-up
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526280
TI  - Anterograde neuronal tracing of retinohypothalamic projections in the hamster-
      possible innervation of substance P-containing neurons in the suprachiasmatic
      nucleus.
AB  - The retinohypothalamic tract (RHT) in the Djungarian hamster Phodopus sungorus
      was studied using anterograde neuronal transport of cholera toxin subunit B (CTB)
      following unilateral intraocular injection. A major projection terminates
      bilaterally in the hypothalamic suprachiasmatic nuclei (SCN). In the anterior
      ventral SCN, a light ipsilateral predominance was evident. In the medial SCN,
      labelling was concentrated laterally where it was seen over the dorso-ventral
      extension of the nuclei, pronounced contralaterally to the site of CTB injection,
      which was even more characteristic in the posterior aspects of the nuclei.
      Labelled fibers and terminals were observed in the supraoptic nuclei, but not in
      lateral and paraventricular hypothalamic regions. Additional experiments
      utilizing double immunofluorescence of CTB and of substance P (SP) in the SCN
      showed that SP-containing perikarya were particularly observed in a central
      portion of the nucleus, where CTB-stained terminals were accumulated in the
      vicinity of immunoreactive cell bodies, fibers and terminals. Our data provide
      preliminary morphological evidence for the regulation of SCN function by retinal
      afferents and may explain the circadian and photoperiodic fluctuations in the
      amount of SP in the SCN.

PMID- 7526279
TI  - L-NAME modulates glutamate accumulation induced by K(+)-depolarization but not by
      forebrain ischaemia in the rat striatum.
AB  - The accumulation of extracellular glutamate and aspartate in the striatum of rats
      during ischaemia was examined by perfusion with Ca(+)-free medium and treatment
      with the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L
      NAME). Male Wistar rats were subjected to 30 min ischaemia using the 4-vessel
      occlusion model or high K(+)-depolarization. Extracellular glutamate and
      aspartate were monitored by in vivo microdialysis. Perfusion with Ca(2+)-free
      medium and systemic administration or local perfusion of L-NAME reduced the K(+)
      evoked glutamate accumulation but not the ischaemia-induced glutamate
      accumulation. The aspartate concentration was unaffected in both conditions. Our
      data suggest that the extracellular glutamate and aspartate originates from a
      Ca(2+)-independent pool during forebrain ischaemia and is not modulated by nitric
      oxide. In high K(+)-depolarization the accumulated glutamate may arise, at least
      in part, from enhanced vesicular release and is modulated by nitric oxide.

PMID- 7526281
TI  - Current density analysis of outward currents in acutely isolated rat entorhinal
      cortex cells.
AB  - Entorhinal cortex stellate and pyramidal cells were acutely isolated from
      juvenile rats. Using the whole-cell configuration of the patch-clamp method
      outward potassium currents were recorded. A fast transient A-current and a
      sustained outward current could be measured in both stellate and pyramidal cells.
      The A-current density was significantly larger in pyramidal cells than in
      stellate cells. In contrast, stellate cells possessed a larger current density of
      the delayed rectifier current as well as the Ca2+ activated K+ current than
      pyramidal cells. Moreover, superficial stellate cells exhibited large delayed
      rectifier currents and only small A-currents while entorhinal cortex deep layer
      pyramidal cells displayed larger A-currents than delayed rectifier currents.

PMID- 7526284
TI  - Single channel properties of the 5-HT3 subtype of serotonin receptor in primary
      cultures of rodent hippocampus.
AB  - Whole cell and outside-out patch clamp recordings were obtained from primary
      cultures of rat and mouse hippocampal neurons. Serotonin (5-HT) evoked short
      latency fast inward currents in about 5% of neurons. These currents reversed near
      0 mV, showed inward rectification, and were inhibited by the 5-HT3 receptor
      antagonists ICS 205-930, ondansetron and tubocurare. 5-HT activated single
      channel currents in 14 of 24 membrane patches obtained from neurons which showed
      5-HT3-activated whole cell currents; mean amplitude of channel openings was 0.95
      +/- 0.09 pA at -100 mV. Chord conductances measured at -80 and -160 mV were 8.3
      and 10.5 pS, respectively. 5-HT-induced unitary currents were blocked reversibly
      by tubocurare (1 microM), ICS 205-930 (30 nM) and ondansetron (100 nM). Thus,
      single-channel properties of 5-HT3 receptors in hippocampal neurons are similar
      to those present in peripheral neurons and do not exhibit solely the sub
      picosiemen conductance characteristic of the neuroblastoma and neuroblastoma
      derived cloned 5-HT3 receptor.

PMID- 7526282
TI  - Presence of constitutive type nitric oxide synthase in cultured astrocytes
      isolated from rat cerebra.
AB  - To define whether astrocytes express a constitutive nitric oxide synthase (NOS),
      nitric oxide (NO) producing activity in astrocytes derived fetal rat cerebra was
      examined. We found that the addition of an NOS inhibitor to cultures caused
      decrease in the basal cGMP levels in unstimulated astrocytes and the decrease was
      dose-dependent. Further, the expression of cNOS activity in unstimulated
      astrocytes was confirmed by histochemical staining for NADPH diaphorase and by
      measuring conversion of L-arginine to L-citrulline. We conclude that cultured
      astrocytes express constitutive NOS, in addition to inducible one.

PMID- 7526283
TI  - Alteration of substance P-mediated vasodilatation and sympathetic
      vasoconstriction in the rat knee joint by adjuvant-induced inflammation.
AB  - The effects of nerve stimulation and topical administration of substance P (SP)
      on the blood flow supplying the rat knee joint were measured using laser Doppler
      perfusion imaging. A comparison was made between the responses found in normal
      knees and those observed in a group of animals with unilateral chronic
      inflammation induced by intra-articular injection of Freund's adjuvant, 1 week
      prior to experimentation. In control knees, nerve stimulation produced a
      frequency-dependent vasoconstriction over the range of 5-30 Hz and application of
      SP caused a dose-dependent vasodilatation. Chronically inflamed joints showed
      virtually no response to either nerve stimulation or SP application, suggesting a
      radical alteration in sympathetic and neuropeptidergic actions.

PMID- 7526285
TI  - Argyrophilic thread-like structure in corticobasal degeneration and supranuclear
      palsy.
AB  - Massive argyrophilic thread-like structures (ATS) are observed in corticobasal
      degeneration and, in varied degrees, in some cases of progressive supranuclear
      palsy. Immunohistochemically, ATS has a full length of phosphorylated tau
      epitopes without ubiquitin. Gallyas- and immuno-electron microscopic observation
      revealed that ATS is a cytoskeletal abnormality occurred in both the inner and
      outer loop of the oligodendroglia. tau-Positive oligodendroglial tangles were
      distributed in the same region as ATS.

PMID- 7526286
TI  - Distribution of glutamate- and GABA-immunoreactive neurons projecting to the
      vasomotor center of the intermediolateral nucleus of the lower thoracic cord of
      Wistar rats: a double-labeling study.
AB  - The purpose of this study was to survey distribution of glutamatergic and
      GABAergic neurons in the brainstem with projections to the vasomotor center in
      the intermediolateral nucleus of the T11 segment of Wistar rats. This was done
      with retrograde transport of WGA-HRP and immunoreaction to glutamate and GABA.
      HRP/glutamate-labeled neurons were distributed in the rostral ventrolateral
      medulla (RVLM, 29%), A5 noradrenaline cell area (16%), paraventricular nucleus of
      the hypothalamus (14%) and caudal ventrolateral medulla (CVLM, 11%), while
      HRP/GABA-labeled neurons in the RVLM (65%) and CVLM (24%). This indicates that
      the glutamatergic and GABAergic neurons projecting to the spinal vasomotor center
      originate mainly from the RVLM and CVLM.

PMID- 7526287
TI  - Immunolocalisation of chromogranin B, secretogranin II, calcitonin gene-related
      peptide and substance P at developing and adult neuromuscular synapses.
AB  - The localisation of chromogranin B, secretogranin II, calcitonin gene-related
      peptide and substance P was characterised by the use of indirect
      immunofluorescence techniques at neuromuscular junctions in frog, mouse and rat
      muscles. We found that chromogranin B, secretogranin II and calcitonin gene
      related peptide are co-expressed in the frog, 1 week old mouse and 1 week old rat
      endplates. Substance P immunoreactivity could only be detected in frog muscles.

PMID- 7526289
TI  - The effect of gold salts on substance P levels in rheumatoid arthritis.
AB  - The effect of gold salt therapy on substance P immunoreactivity levels in plasma
      and synovial fluid was studied in 42 patients with rheumatoid arthritis.
      Decreased levels of synovial fluid substance P, although not statistically
      significant, were found in rheumatoid patients who were currently receiving gold
      therapy when compared to either those patients previously treated or to those who
      never received this therapy. In addition, we found that patients who received
      more than 1000 mg of gold salts had significantly lower levels of substance P in
      synovial fluid than those treated with lower doses. Our results, therefore, seem
      to support the hypothesis that gold salts appear to be slow-acting neurotoxic
      drugs that significantly decrease the intrasynovial concentrations of substance
      P, a well-known inflammatory neuropeptide, in arthritis patients.

PMID- 7526288
TI  - The actions of L-687,384, a sigma receptor ligand, on NMDA-induced currents in
      cultured rat hippocampal pyramidal neurons.
AB  - The actions of the sigma receptor ligand L-687,384 were studied on N-methyl-D
      aspartate (NMDA)-induced currents recorded from outside-out patches obtained from
      cultured rat hippocampal pyramidal neurons and on NMDA-evoked rises in [Ca2+]i in
      the same preparation. L-687,384 did not change the magnitudes of unitary NMDA
      currents or frequency of channel-openings but diminished channel-open probability
      by decreasing mean open time. This action was consistent with a voltage-dependent
      open-channel block of the NMDA channel by L-687,384 with a blocking rate constant
      of 5.9 x 10(6) M-1 s-1 at -80 mV. L-687,384 also reduced NMDA-evoked rises in
      [Ca2+]i in Fura-2-loaded neurons with an apparent IC50 value of 49 +/- 8 microM.
      The results demonstrate that L-687,384 acts as an antagonist at the NMDA receptor
      channel complex.

PMID- 7526290
TI  - Critical period for degradation of adult rat retinal ganglion cells and their
      regeneration capability after axotomy.
AB  - The optic nerve (ON) in adult rats was transected intraorbitally followed by
      retrograde labelling of retinal ganglion cells (RGCs) with fluorescence dye
      (DiI). A two phase reduction of axotomized RGCs was represented in the retina
      until 15 days after ON transection. The critical period of RGC loss is around 7
      days after axotomy. In this period, the capability of neurite regeneration from
      RGCs in culture was strongly intensified by ON transection. These findings
      indicate that the 7th day after axotomy is important for both RGC survival and
      regeneration.

PMID- 7526291
TI  - Characterization and application of microdialysis probes with an active exchange
      length compatible with small-size brain nuclei in the rat.
AB  - We communicated the construction, characterization and application of
      microdialysis probes with an active exchange length that is suitable for
      experiments involving small-size nuclei in rat brain. Using substance P (SP) as
      the test substance, we determined that probes with an active exchange length of
      180-200 microns exhibited an in vitro recovery of 14.2 +/- 0.8% and in vivo
      recovery at the nucleus tractus solitarii (NTS) of 24.9 +/- 1.7% for the
      undecapeptide, calibrated at an infusion rate of 1 microliter/min. We also
      demonstrated that microinfusion of SP via these probes into the NTS allowed for a
      correlation of changes in tissue levels of both SP (exogenous substance) and
      norepinephrine (endogenous substance) with alterations in baroreceptor reflex
      responses (physiologic phenomenon).

PMID- 7526292
TI  - Muscarinic acetylcholine receptors on an identified motor neurone in the
      cockroach, Periplaneta americana.
AB  - Muscarinic acetylcholine receptors (mAChRs) on the cell body of the fast coxal
      depressor motor neurone (Df) in the metathoracic ganglion of the cockroach
      Periplaneta americana were investigated using electrophysiological methods.
      Muscarinic agonists, arecoline and oxotremorine, induced dose-dependent
      depolarizations on motor neurone Df. McN-A-343, a vertebrate mAChR M1 subtype
      selective agonist, failed to induce any responses when tested on the same neurone
      at concentrations of up to 1.0 x 10(-4) M. The order of effectiveness of a series
      of muscarinic antagonists on the mAChRs of motor neurone Df is as follows:
      scopolamine > atropine > pirenzepine. 4-DAMP (1.0 x 10(-5) M) had only a weak
      blocking effect and AF-DX 116 (1.0 x 10(-5) M) was completely inactive. The
      pharmacological profile of muscarinic responses on motor neurone Df reveals a
      novel type of insect mAChR.

PMID- 7526293
TI  - NMDA receptor mRNA expression in NOS-containing neurons in the spinal trigeminal
      nucleus of the rat.
AB  - The spinal trigeminal nucleus (STN) is involved in the transmission of orofacial
      sensory information. Nitric oxide (NO), an important neuromessenger, and the
      glutamate receptor subtype, NMDA NR1, have been implicated in nociception in the
      STN. However, the anatomical relationship of NO and NMDA NR1 has not been
      investigated within this nucleus. Using both immunocytochemical (against NO
      synthase; NOS) and in situ hybridization studies of NMDA NR1 receptor mRNA, we
      found that NOS-containing neurons in the STN expressed more mRNA for NR1 than did
      non-NOS-containing neurons in the STN. These data suggest that NMDA activation
      may lead to NO production in the STN and is consistent with previous studies,
      implicating both NMDA and NO in nociception.

PMID- 7526295
TI  - Newly observed pre-cerebellar neurons in the rat are homologous to neurons in the
      nucleus conterminalis in man.
AB  - After injection of wheat germ agglutinin-horseradish peroxidase into the rat
      cerebellum, a small number of large neurons were labeled in a narrow area between
      the pyramidal tract and the inferior olivary nucleus. These labeled neurons are
      distinct from previously described pre-cerebellar neurons in distribution and
      neuronal size. Together with the known strong acetylcholinesterase activity in
      this area, the results of this study show that these neurons comprise a novel pre
      cerebellar nucleus, which I have designated 'nucleus subolivaris'. Based upon
      morphological characteristics, it is likely that this small pre-cerebellar
      nucleus is the homologue of the nucleus conterminalis in man.

PMID- 7526296
TI  - [3H]Rolipram binding and phosphodiesterase activity in neuroblastoma N18TG-2 and
      glioma C6Bu-1.
AB  - To clarify the functional significance of type IV phosphodiesterase (PDEIV) in
      neurons and glia cells [3H]rolipram binding and phosphodiesterase (PDE) activity
      were examined in cytosol and membrane fractions of neuroblastoma N18TG-2 and
      glioma C6Bu-1 cells. [3H]Rolipram binding was highly observed in cytosolic
      fractions of N18TG-2 compared to C6Bu-1. Binding was hardly observed in membrane
      fractions of both types of cells. Rolipram strongly (70%) inhibited the
      hydrolytic activity of cAMP in cytosolic fractions of N18TG-2. The activity in
      cytosol fractions of C6Bu-1 was slightly (20%) inhibited by rolipram. These
      results suggest that PDEIV plays important roles in neurons.

PMID- 7526294
TI  - Polyamines inhibit nitric oxide synthase in rat cerebellum.
AB  - The polyamines spermine, spermidine and putrescine share some basic structural
      features with L-arginine, the substrate of nitric oxide (NO) synthase. The
      effects of the polyamines on neuronal NO synthase activity were studied in
      cytosolic preparations of rat cerebellum and cultured cerebellar granule neurons.
      Spermine, spermidine and putrescine all inhibited the conversion of [3H]L
      arginine to [3H]L-citrulline by NO synthase, with the following rank order of
      potency: spermine > spermidine > putrescine. These inhibitory effects of the
      polyamines on [3H]L-citrulline formation were also observed in intact cultured
      cerebellar granule neurons upon stimulation of N-methyl-D-aspartate (NMDA)
      receptors. Evidence was obtained, however, that endogenous polyamines are not
      involved in regulation of NMDA-stimulated NO synthase activity. Thus, the
      observed inhibitory effects of exogenous polyamines might not reflect a
      physiological role in modulating NO generation in neurons.

PMID- 7526297
TI  - CCK-8-evoked cationic currents in substantia nigra dopaminergic neurons are
      mediated by InsP3-induced Ca2+ release.
AB  - Our recent study demonstrated that by activating CCK-A receptors, CCK-8 excites
      substantia nigra (SN) dopaminergic (DA) neurons via increasing a non-selective
      cationic conductance. In the present study, we further studied the molecular
      mechanism by which CCK-8 induces cationic currents in SN DA neurons. CCK-8-evoked
      inward currents were inhibited by the intracellular perfusion of GDP-beta-S (1
      mM). In DA neurons internally perfused with GTP-gamma-S (0.5 mM), the inward
      currents produced by CCK-8 became irreversible. Pretreating DA neurons with 500
      ng/ml pertussis toxin (PTX) did not significantly affect the ability of CCK-8 to
      induce cationic currents. Intracellular application of heparin (2 mg/ml), an
      inositol 1,4,5-trisphosphate (InsP3) receptor antagonist, and buffering
      intracellular calcium with the Ca(2+)-chelator BAPTA (10 mM) suppressed CCK-8
      evoked cationic currents. Dialyzing DA neurons with protein kinase C (PKC)
      inhibitors, staurosporine and PKC(19-31), failed to prevent CCK-8 from generating
      cationic currents. It is concluded that PTX-insensitive G-proteins mediate CCK-8
      induced enhancement of cationic conductance of SN DA neurons. The coupling
      mechanism via G-proteins is likely to involve the generation of InsP3, and
      subsequent InsP3-evoked Ca2+ release from the intracellular store results in
      activating the non-selective cationic conductance.

PMID- 7526298
TI  - Induction in the rat hippocampus of long-term potentiation (LTP) and long-term
      depression (LTD) in the presence of a nitric oxide synthase inhibitor.
AB  - Several recent studies have suggested a critical role for nitric oxide (NO)
      production in hippocampal LTP and LTD. In this study we show that normal LTP and
      LTD can be induced in rat hippocampal slices incubated in the NO synthase
      inhibitor L-NG-nitroarginine (NOArg) (100 microM). A test of NMDA-stimulated cGMP
      production demonstrated that incubation of slices in 100 microM NOArg effectively
      inhibited NO synthase. Our results suggest that NO synthase activity may not be
      required for the generation of LTP or LTD in CA1 of rat hippocampus.

PMID- 7526300
TI  - Peripheral myelin P0 protein mediates neurite outgrowth of cortical neurons in
      vitro and axonal regeneration in vivo.
AB  - Peripheral myelin P0 protein is a homophilic adhesion molecule of immunoglobulin
      superfamily to compact myelin structure. In addition to its roles in formation
      and maintenance of myelin, P0 shows neurite-outgrowth promotion activity of
      dorsal root ganglions. In this paper, we examined biological activity of P0 in
      central nervous system (CNS). Neurite outgrowth of cortical neurons of rat embryo
      was markedly promoted in the co-culture on C6 transformants expressing P0
      protein. The neurite outgrowth was not inhibited by the P0-glycopeptide but
      specifically inhibited by the anti-P0 monoclonal antibody recognizing the
      extracellular peptide of P0. In in vivo studies, we observed significant axonal
      regeneration into grafts only in animals implanted with P0-expressing
      transformants after spinal one-third transection. These results suggest that P0
      protein has promoting activity on the neurite elongation in CNS as well as in
      peripheral nervous system.

PMID- 7526299
TI  - Substance P released endogenously by high-intensity sensory stimulation
      potentiates purinergic inhibition of nociceptive dorsal horn neurons induced by
      peripheral vibration.
AB  - To investigate the interaction at the spinal level of endogenously released
      substance P with the effects of endogenously released adenosine, extracellular
      single-unit activity was recorded from dorsal horn neurons in the anesthetized
      cat. Vibration to the skin inhibited on-going activity of nociceptive neurons; 20
      mg/kg caffeine reversibly blocked this inhibition, indicating mediation via
      adenosine receptors. In half of the cases, this inhibition was potentiated by
      iontophoretic application of substance P. High-intensity electrical stimulation
      to a sensory nerve produced excitation which was blocked by an NK-1 (substance P)
      receptor antagonist, implicating an endogenous neurokinin. When electrical
      stimulation preceded the vibrational stimulus, the inhibitory effect of vibration
      was potentiated. Thus, we suggest that endogenous substance P may potentiate the
      inhibitory response to endogenous adenosine. The results have important
      implications for integration of inputs from different sensory modalities,
      especially as they relate to nociception and pain.

PMID- 7526301
TI  - Increased oxidation of pineal serotonin as a possible explanation for reduced
      melatonin synthesis in the aging Djungarian hamster (Phodopus sungorus).
AB  - Groups of young adult (1.7 months) and old adult (9.7 months) female Djungarian
      hamsters were exposed to short-day photo-periods (SD; 8L:16D) or long-day
      photoperiods (LD; 16L:8D) for 6 weeks. Pineal and serum melatonin rhythms were
      dampened in old SD animals when compared with young SD animals. The melatonin
      precursor serotonin showed diurnal variations with opposite phases to melatonin
      synthesis. However, pineal serotonin levels were even lower in old SD animals
      than in young SD animals, contrary to the expected accumulation of the precursor.
      The synthesis of a metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA),
      was significantly lower in younger hamsters, under both photoperiods. These
      results indicate that the age-associated decline in the production of melatonin
      is a consequence of an increased oxidation of its precursors.

PMID- 7526302
TI  - Species and age-dependent differences of functional coupling between opioid delta
      receptor and G-proteins and possible involvement of protein kinase C in striatal
      membranes.
AB  - [D-Ser2,Leu5]-enkephalin-Thr6 (DSLET) and [D-Pen2,5]-enkephalin (DPDPE), both
      delta-agonists, stimulated the high affinity GTPase in the rat striatal membranes
      in a naltrindole-reversible manner. Similar stimulation was also observed in the
      striatal membrane preparations of 16-week-old guinea pigs, while not in those
      preparations of 4-week-old ones. When calphostin C, a protein kinase C inhibitor,
      was added to the reaction mixture, DSLET showed a marked stimulation in this
      activity in 4-week guinea pig striatal membranes. There was no effect of KT5720,
      a cyclic AMP-dependent protein kinase inhibitor, on such delta-opioid-mediated
      responses. These findings suggest that protein kinase C is locally involved in
      the functional uncoupling of delta-receptors to G-proteins in the striatum of
      young guinea pigs.

PMID- 7526304
TI  - The carbohydrate epitope HNK-1 is present on all inactive, but not on all active
      forms of chicken butyrylcholinesterase.
AB  - The HNK-1 epitope as a hallmark of many cell adhesion molecules is supposed to
      convey positive cellular interactions. Here, we report that in the adult chick
      the HNK-1 epitope is absent from active serum butyrylcholinesterases (BChE), but
      is strongly expressed on all inactive serum BChEs and on active brain BChE. These
      data further support roles of cholinesterases in cell adhesion, particularly so
      for their inactive forms. Moreover, we show that the HNK-1-positive BChEs belong
      to different types of glycoproteins.

PMID- 7526303
TI  - C1-3 adrenergic medullary neurones project to the paraventricular thalamic
      nucleus in the rat.
AB  - Adrenergic afferents to the thalamus are almost entirely concentrated in the
      paraventricular thalamic nucleus (PV). The origins of this projection from
      medullary C1-3 neurones were quantified, using a combination of retrograde
      fluorescent markers and immunocytochemical localisation for phenylethanolamine N
      methyltransferase (PNMT) in the rat. C1 neurones contributed 51%, C2 29% and C3
      20% of the total adrenergic input. Many apparently non-adrenergic retrogradely
      labelled neurones were also found amongst the C1-3 neurones. The C3 region
      contained the largest adrenergic population (67%) of retrogradely labelled
      neurones. The neuronal networks associated with PV suggest a role for these
      adrenergic projections in regulating specific autonomic, locomotor and
      behavioural events.

PMID- 7526305
TI  - Maternal serum pregnancy-associated plasma protein A and fetal nuchal
      translucency thickness for the prediction of fetal trisomies in early pregnancy.
AB  - OBJECTIVE: To determine if the risk for fetal trisomies during the first
      trimester of pregnancy can be derived by combining data from maternal serum
      pregnancy-associated plasma protein A (PAPP-A) and fetal nuchal translucency
      thickness. METHODS: Pregnancy-associated plasma protein A was measured in samples
      from 87 singleton pregnancies with fetal chromosomal abnormalities (45 trisomy
      21, 19 trisomy 18, eight trisomy 13, 11 sex chromosome aneuploidies, four
      triploidies) and 348 chromosomally normal controls at 10-13 weeks' gestation.
      Likelihood ratios for trisomies 21, 18, and 13 in relation to PAPP-A, in
      multiples of the normal median (MoM) for crown-rump length, were derived from the
      overlapping gaussian frequency distribution curves for normal and abnormal
      pregnancies. RESULTS: In the chromosomally normal group, maternal serum PAPP-A
      correlated significantly with fetal crown-rump length (r = 0.421, P < .0001). In
      the chromosomally abnormal group, the median PAPP-A was significantly lower than
      in the normal controls. The respective median values expressed in MoM for
      trisomies 21, 18, and 13 and other aneuploidies were 0.5 MoM (90% confidence
      interval [CI] 0.09-1.67, z = 6.0, P < .001), 0.17 MoM (90% CI 0.06-1.45, z = 6.6,
      P < .001), 0.25 MoM (90% CI 0.10-0.62, z = 4.5, P < .001), and 0.72 MoM (90% CI
      0.09-2.48, z = 2.2, P < .05), respectively. There was no significant linear
      association between PAPP-A and fetal nuchal translucency thickness in either the
      chromosomally normal (r = -0.01, P = .89) or abnormal groups (r = -0.19, P =
      .08). CONCLUSION: The risks for fetal trisomies at 10-13 weeks' gestation can be
      derived by combining data on maternal age, maternal serum PAPP-A, and fetal
      nuchal translucency thickness.

PMID- 7526306
TI  - Increased concentrations of cytokines interleukin-6 and interleukin-1 receptor
      antagonist in plasma of women with preeclampsia: a mechanism for endothelial
      dysfunction?
AB  - OBJECTIVE: To determine if plasma concentrations of defined cytokines are
      increased in women with preeclampsia, and to correlate any increases with the
      elevated concentrations of the vascular cell adhesion molecule (VCAM)-1. METHODS:
      Twenty primigravidas with preeclampsia were compared to 20 healthy primigravidas.
      Plasma levels of cytokines, tumor necrosis factor-alpha (TNF alpha), interleukin
      (IL)-6, IL-8, IL-1 beta, IL-1 receptor antagonist (IL-1ra), granulocyte
      macrophage-colony-stimulating factor (GM-CSF), and VCAM-1, were measured by
      enzyme-linked immunosorbent assay. RESULTS: Concentrations of IL-6 and IL-1ra
      were significantly higher (P < .01) in preeclamptic women (2.56 and 251.85 pg/mL,
      respectively) compared to normal pregnant patients (2.06 and 142.00 pg/mL,
      respectively). There were no significant changes in concentrations of TNF alpha,
      IL-8, GM-CSF, and IL-1 beta in preeclamptic patients (14.09, 50.52, 125.8, and
      2.08 pg/mL, respectively) compared to normal patients (11.96 44.46, 121.3, and
      2.01 pg/mL, respectively). Serum concentrations of VCAM-1 were increased in women
      with preeclampsia (preeclamptic group 841.9 +/- 49.7 ng/mL, control group 560.2
      +/- 47.9 ng/mL; t = 3.673, P < .001). Interleukin-6 and IL-1ra concentrations
      correlated with VCAM-1 concentrations (IL-6: r = 0.539, z = 2.9, P < .005; IL
      1ra: r = 0.451, z = 2.428, P < .02). CONCLUSIONS: Increased cytokine
      concentrations may contribute to the endothelial damage that occurs with
      preeclampsia and may explain the mechanism underlying leukocyte activation in
      this disorder. The increased cytokine concentration may also be responsible for
      the endothelial adhesion that accompanies preeclampsia.

PMID- 7526307
TI  - A simple technique to manage malignant pericardial effusion with a local
      instillation of bleomycin in non-small cell carcinoma of the lung.
AB  - To examine the efficacy of bleomycin on the local control of malignant
      pericardial effusion, we prospectively conducted a clinical trial consisting of
      continuous pericardial drainage and a local instillation of bleomycin. In the
      current study, we treated 7 patients, who suffered from malignant pericardial
      effusion with cardiac tamponade due to advanced-stage non-small cell carcinoma of
      the lung. The pericardial effusions were continuously drained through an echo
      guided inserted catheter. After the effusions were drained as completely as
      possible, 5 mg of bleomycin were instilled locally via the catheter. In all
      patients but one, the draining catheter could be successfully removed. The
      duration of drainage ranged from 4 to 13 days (mean: 9.2 days). Five of the 7
      patients achieved a complete remission of pericardial effusions, which was
      maintained until death or the last day of follow-up. Intrapericardial bleomycin
      treatment was thus found to be effective on malignant pericardial effusions
      without any adverse effects. However, a further study comparing the effect of
      pericardial instillation of bleomycin versus drainage alone would be needed for
      the determination of the usefulness of bleomycin.

PMID- 7526309
TI  - Choroidal filling in age-related macular degeneration: indocyanine green
      angiographic findings.
AB  - We studied the choroidal filling patterns in 145 patients with age-related
      macular degeneration (AMD), looking for a correlation with choroidal
      neovascularization (CNV). We found a correspondence in 71% of cases between the
      site of the CNV and watershed areas and in 59% of cases between the CNV and areas
      of 'delayed choroidal filling'. These data support the hypothesis of a
      relationship between areas of presumed choroidal ischemia and evolution of AMD
      complicated with CNV.

PMID- 7526310
TI  - Distribution of hyaluronan in the middle and inner ear. A light microscopical
      study in the rat using a hyaluronan-binding protein as a specific probe.
AB  - The histochemical distribution of hyaluronan (hyaluronic acid, HYA) was analyzed
      in middle and inner ear tissues from rats by use of microwave-aided fixation, a
      hyaluronan-binding protein and the avidin-biotin/peroxidase staining procedure.
      In the middle ear HYA was mainly localized in the pars flaccida, the ossicles,
      the round window membrane and in the endomysium of the middle ear muscles. The
      subepithelial stroma of the Eustachian tube was strongly HYA-positive. In the
      inner ear, the spiral ligament of the cochlea and the connective tissue
      surrounding the nerve fibers emerging from the crista ampullaris stained
      intensely for HYA. Except for a weak staining of the basilar membrane, the Corti
      organ was devoid of HYA. The heterogenous distribution of HYA may indicate its
      specific involvement in middle and inner ear physiology and pathology.

PMID- 7526308
TI  - Taxol (paclitaxel) plus recombinant human granulocyte colony-stimulating factor
      in the treatment of metastatic breast cancer.
AB  - We treated 28 patients who had no prior chemotherapy for stage IV breast cancer
      and 51 patients with extensive prior exposure to other chemotherapeutic agents
      with a 24-hour infusion of Taxol (paclitaxel) as a single agent. Prophylactic
      recombinant human granulocyte colony-stimulating factor was administered
      routinely to ameliorate the anticipated dose-limiting toxicity of neutropenia.
      Nonhematologic toxicity was mild to moderate in most cases. Taxol was more active
      in patients with chemotherapy-naive stage IV disease, but activity was also
      observed in extensively treated patients as well. There is a strong clinical
      suggestion of at least partial noncross-resistance with doxorubicin. Taxol is a
      very promising agent for the treatment of metastatic breast cancer; its optimal
      application in this disease will be the subject of future trials.

PMID- 7526311
TI  - Functional imaging of the human olfactory cortex by magnetic resonance imaging.
AB  - Our understanding of the neural mechanism of human olfaction is still equivocal.
      Several recent reports document that functional magnetic resonance imaging (MRI)
      has a potential to visualize dynamic brain function in humans without invasion.
      In the present study, we applied functional MRI with odor stimulation for the
      purpose of clarifying the localization of olfactory cortices in the human. We
      obtained a significant increase in cerebral blood flow in the piriform cortex,
      orbitofrontal cortex, and inferior medial frontal lobe, corresponding to
      olfactory cortices. These results suggest that, in the near future, precise
      diagnosis of the patients with olfactory disorders will be possible using
      functional MRI with odor stimulation.

PMID- 7526313
TI  - [Congenital analgesia. Part IV. Adolescence, adulthood, labor (follow-up case
      report)].
AB  - Congenital analgesia in a girl (now woman) is reported for the fourth time. The
      former reported case is now 27 years old, her pain sensitivity is normal over the
      entire body. The fourth communication presents her postadolescent and later her
      young adult life, reporting her two deliveries, producing healthy babies. On the
      basis of these facts congenital analgesia does not seem genetically determined.

PMID- 7526314
TI  - [Dealing with cancer pain].

PMID- 7526312
TI  - Methotrexate, vinblastine, epidoxorubicin, and bleomycin as second-line
      chemotherapy for recurrent and/or metastatic squamous cell carcinoma of the head
      and neck.
AB  - Thirty evaluable patients with recurrent and/or metastatic squamous cell
      carcinoma of the head and neck region previously treated with cisplatin-based
      chemotherapy were treated with a combination of methotrexate, vinblastine,
      epidoxorubicin, and bleomycin as second-line chemotherapy. Besides surgery and/or
      radiotherapy all patients had previously received chemotherapy as induction
      therapy or as palliation for recurrent disease. Only 20% of patients achieved a
      partial objective response with a mean duration of 5.6 months (range 3.2-6.2),
      and 30% of patients had a stabilization of disease with a mean duration of 4.2+
      months (range 3.8-6.0). Patients who responded had rhinopharyngeal carcinoma,
      poorly differentiated histology, or they had not been previously treated with
      radiotherapy. All remaining patients (50%) progressed. Toxicity was significant
      with grade 3-4 leukopenia in 30% of cases, grade 2-3 mucositis in 40% of
      patients, and grade 2-3 vomiting in 43% of cases. In consideration of the dismal
      clinical results and of the significant toxicity recorded, we do not recommend to
      use this combination as second-line therapy in recurrent head and neck cancer.
      Further chemotherapy should be reserved to carefully selected cases with a
      reasonably high chance of response.

PMID- 7526315
TI  - Identification of major tyrosine-phosphorylated proteins in Csk-deficient cells.
AB  - Csk is a non-receptor protein-tyrosine kinase that acts as a negative regulator
      of Src family tyrosine kinases. Csk-deficient mouse embryos exhibited
      developmental defects including inability to turn and impaired formation of
      neural tube. In these embryos, an accumulation of tyrosine phosphorylated
      proteins was observed as a consequence of constitutive activation of Src family
      kinases. In order to identify those tyrosine phosphorylated proteins, we
      established a Csk-deficient cell line from embryos lacking both Csk and the anti
      oncogene product p53. On surveying several proteins known as Src substrates, we
      found that phosphorylation level of p80/85 (cortactin) was markedly elevated in
      the Csk-deficient cells. Enhancement of cortactin phosphorylation was also seen
      in Csk-deficient embryos. Furthermore, immunoprecipitated Src was able to
      directly phosphorylate cortactin in vitro. Thus, we suggest that cortactin is a
      good substrate of activated Src family kinases in vivo and may play important
      roles in signaling pathways mediated by Src family kinases.

PMID- 7526317
TI  - Expression of mutationally activated G alpha s stimulates growth and
      differentiation of thyroid FRTL5 cells.
AB  - The alpha subunit of the GTP-binding protein Gs mediates hormonal stimulation of
      adenylyl cyclase. Human pituitary and thyroid tumours harbour mutations of G
      alpha s that constitutively activate the protein by inhibiting its intrinsic
      GTPase activity. We have investigated the mitogenic action of mutationally
      activated alpha s in thyroid FRTL5 cells, a cell line dependent upon thyroid
      stimulating hormone (TSH) for both growth and differentiation. Introduction of
      alpha s carrying the substitution of glutamine-227 with leucine (Q227L alpha s)
      by retroviral infection of FRTL5 cells resulted in the expected stimulation of
      membrane adenylyl cyclase activity and in increased intracellular accumulation of
      cAMP. Measurements of cytosolic Ca2+ levels did not detect any concomitant effect
      on the polyphosphoinositide-Ca2+ signalling pathway. Expression of Q227L alpha s
      conferred to FRTL5 cells the ability to synthesize DNA in the absence of TSH, as
      revealed by [3H]thymidine incorporation experiments, and to proliferate
      independently of the mitogenic hormone, although with a rate of growth slower
      than that observed with TSH stimulation. The effect of Q227L alpha s on cell
      proliferation was associated with the constitutive activation of iodide uptake.
      The results indicate that expression of mutationally activated G alpha s is
      sufficient to bypass the requirement for TSH and promotes autonomous growth and
      activation of thyroid-specific differentiated functions in FRTL5 cells.

PMID- 7526316
TI  - Myc induces cyclin D1 expression in the absence of de novo protein synthesis and
      links mitogen-stimulated signal transduction to the cell cycle.
AB  - Mitogen-activated signal transduction frequently leads to the induction of the c
      myc proto-oncogene, but the subsequent molecular events downstream of Myc protein
      expression which promote cell cycle progression remain unclear. To study Myc
      specific effects, without the complexity of the broader proliferative response
      evoked by serum, we employed the MycER-inducible system in the non-transformed
      Rat-1 cell line. We demonstrate that activation of wild-type, but not mutant,
      MycER is sufficient to transiently induce cyclin D1 RNA as well as protein
      expression to physiological levels, and promote G0/G1 to S phase transition of
      the cell cycle. Stimulation of endogenous cyclin D1 RNA is rapid and clearly
      evident within 30 min of MycER-activation, reaching a peak at 3 h. Nuclear run-on
      analysis demonstrates that this induction occurs at the transcriptional level
      with a fivefold increase in the rate of transcription. Moreover, MycER induces
      cyclin D1 transcription with equal efficacy in the presence or absence of de novo
      protein synthesis. Our work shows that Myc and cyclin D1 lie consecutively in a
      major proliferation-control pathway, and together create a pivotal connection
      between signal transduction and cell cycle control.

PMID- 7526319
TI  - [Auditory brain stem responses in children with the delayed speech development].
AB  - The central transmission time in ABR examinations were evaluated in a group of
      young children with the delayed speech. The age of these children were between 2:
      6/12 and 4 years. They spoke only some words, have a good hearing, good
      intelligence quotient (IQ) in nonverbal tests and have a good speech
      understanding. Their central transmission times (interwave intervals I-III, III
      V, I-V) were longer than in the normal children. This latency elongation may be
      the sing of the delayed myelinization of the neural tracts, a probable cause also
      of their delayed speech development.

PMID- 7526318
TI  - Mutations in p53 produce a common conformational effect that can be detected with
      a panel of monoclonal antibodies directed toward the central part of the p53
      protein.
AB  - Human p53 displays two immunodominant regions localized in the amino and carboxy
      termini of the protein. Using a truncated p53 (residues 66 to 361), we selected
      eight new monoclonal antibodies directed to the central part of the protein. We
      identified the epitopes recognized by seven out of eight antibodies with a set of
      overlapping peptides. One of these antibodies had an epitope similar to PAb240,
      whereas the others recognized novel and diverse antigenic determinants. Using a
      series of 19 p53 mutants, we show that the behavior of several of the new
      monoclonal antibodies is similar to that of PAb240 despite their various epitope
      localizations. This suggests that different mutations in the p53 protein induce
      an overall conformational change that can be detected by various monoclonal
      antibodies directed toward the central part of the protein.

PMID- 7526321
TI  - Possible protective immunity in human opisthorchiasis.
AB  - Chronic infections with the liver flukes Opisthorchis viverrini and Clonorchis
      sinensis affect over 30 million people in southeastern Asia. With ongoing
      exposure, reinfection readily occurs following curative treatment and cumulative
      infections result in significant morbidity and a predisposition to
      cholangiocarcinoma. Though protective immunity has never been described in human
      opisthorchiasis, heterogeneity in worm burden occurs and a small number of
      exposed residents of endemic areas remain apparently uninfected. To explore the
      nature of this heterogeneity, we compared levels of serum antibody (Ab) to O.
      viverrini measured by an enzyme-linked immunosorbent assay in 83 stool egg
      positive and 49 stool egg-negative residents of an O. viverrini-endemic area in
      Thailand. Compared to the egg-positive residents, the egg-negative group had
      significantly higher levels of immunoglobulin (Ig)G, IgA and IgM to adult worm
      homogenate (AWH) and total Ab to metacercaria homogenate (MH). Furthermore,
      immunoblot analyses revealed that a significantly higher proportion of sera from
      the egg-negative residents had IgA reactivity against a 38-kDa AWH antigen and
      IgM reactivity against carbohydrate epitopes of a 42-kDa AWH glycoprotein
      antigen. These findings support a hypothesis that the egg-negative group includes
      individuals who may be immunologically resistant to this usually chronic
      infection.

PMID- 7526320
TI  - Primary sensory neurons exhibit altered gene expression in a rat model of
      neuropathic pain.
AB  - Using a number of complementary anatomical and molecular techniques, we studied
      the effects of chronic constriction injury (CCI), a model of partial nerve injury
      that elicits behavioral hyperalgesia, on primary sensory neurons in the rat.
      Dorsal root ganglia taken from animals with CCI were analyzed for alterations in
      mRNA levels encoding growth-associated protein-43 (GAP-43), calcitonin gene
      related peptide (CGRP), galanin (GAL), neuropeptide Y (NPY), substance P (SP),
      and vasoactive intestinal polypeptide (VIP). We found that GAP-43 expression
      increased 3-fold, peaking between 7 and 14 days after development of the CCI.
      However, within this same 7-14 day time frame, both CGRP and SP mRNAs fell to
      half their normally abundant constitutive levels of expression. The most dramatic
      change in expression occurred for GAL, NPY and VIP mRNAs which all rose rapidly
      (day 3) from non-detectable levels. Similar alterations in gene expression have
      been described after complete sciatic nerve transection or crush.

PMID- 7526322
TI  - Eimeria maxima: ELISA and western blot analyses of protective sera.
AB  - Infection of chickens with Eimeria maxima induces the production of parasite
      specific antisera which can be used passively to protect naive chickens against
      infection. Globulin fractions of these antisera can also be used passively to
      protect chickens. Similarly, intramuscular injection of soybean lectin affinity
      purified gametocyte antigens of E. maxima in Freund's Complete Adjuvant induces
      production of antibodies which are maternally transferred and thereby protect
      hatchlings against E. maxima. ELISA analyses of serum pools having varying
      protective capacities revealed good correlations between passive protection and
      levels of anti-unsporulated oocyst, anti-sporulated oocyst, anti-merozoite and
      anti-gametocyte antibodies. Western blotting demonstrated that the sera mainly
      recognized a number of high molecular weight antigens in all developmental stages
      and that the intensity of the reactions reflected the degree of protection
      induced by the sera. Sera from birds immunized with gametocyte antigens also
      recognized high molecular weight antigens from all the developmental stages, with
      banding patterns remarkably similar to those observed for sera from infected
      birds. Taken together, these results indicate that antibodies can protect against
      infection with E. maxima and these antibodies may recognize and act against
      asexual and/or sexual stages of the parasite.

PMID- 7526324
TI  - Immunohistochemical localization of cystic fibrosis transmembrane conductance
      regulator in human fetal airway and digestive mucosa.
AB  - The cellular distribution of the cystic fibrosis transmembrane conductance
      regulator (CFTR) in human fetal digestive and respiratory mucosa has been studied
      by immunohistochemistry. The streptavidin-biotin immunoperoxidase method was
      applied to paraffin-embedded specimens collected from normal fetuses ranging from
      7 to 39 wk of gestation. By the 7th wk, CFTR protein was strongly detected in the
      yolk sack; in contrast, the staining was weak in the undifferentiated epithelium
      of the intestine and the airways. At 12 wk, the intestine showed strongly and
      diffusely stained enterocytes and a basal cytoplasmic reactivity in the first
      secretory cells. During development, only slight changes could be detected in the
      digestive epithelial distribution of CFTR. In the airways, the CFTR distribution
      followed the cephalocaudal maturation. In the tracheal ciliated cells, the CFTR
      protein was diffusely detected in the cytoplasm as early as 7 wk. After 24-25 wk,
      CFTR was localized at the apical domain of the ciliated cells and was also
      present in the collecting ducts and in the glands of the airways, predominantly
      in the periphery of the acini. Our data suggest that the CFTR is present as early
      as 7 wk during organogenesis and probably plays an important role during fetal
      life. There is an evolution in the CFTR distribution during airway development,
      whereas, in the intestine, CFTR is highly expressed through the epithelium as
      early as 12 wk and keeps the same distribution until birth.

PMID- 7526323
TI  - Epidemiology of Pseudomonas cepacia colonization among patients with cystic
      fibrosis.
AB  - Colonization with Pseudmonas cepacia in patients with cystic fibrosis (CF) has
      been associated with increased morbidity and early death, compared with
      colonization by P. aeruginosa. The mode of acquisition of P. cepacia is not fully
      understood, although person-to-person spread appears likely. Recent epidemiologic
      studies support the importance of social contact in the spread of P. cepacia
      among patients with CF. This study was undertaken to investigate the epidemiology
      of P. cepacia colonization among patients with CF attending the CF clinic at our
      center. Isolates of P. cepacia were collected from patients at two CF treatment
      centers, including ours. Additional isolates were collected from patients without
      CF in the hospital ICU, from other teaching hospitals, and from the environment.
      Profiles of enzymes were obtained by ultrathin polyacrylamide gel electrophoresis
      of P. cepacia extracts. A predominant electromorphic type (ET) was found among P.
      cepacia isolates from patients at both centers, suggesting a common source or
      person-to-person transmission. The majority of hospital isolates fell into a
      single, different ET. Surveillance swabs of respiratory equipment at our CF
      clinic did not grow P. cepacia. Attendance of patients at CF summer camp
      correlated strongly with P. cepacia colonization (P < 0.0001).

PMID- 7526326
TI  - The reactivation of fetal hemoglobin synthesis during anemia of prematurity.
AB  - Increased fetal Hb (HbF) synthesis has been shown to occur during fetal hypoxemia
      and severe anemia. To determine whether increased HbF synthesis occurs during
      anemia of prematurity, the levels of HbF synthesis were correlated with the
      degree of anemia and plasma erythropoietin levels. Thirteen newborn infants born
      at 29.2 +/- 1.7 wk of gestation were studied at a postconceptional age 36.0 +/-
      1.1 wk. Hb levels ranged from 65 to 78 g/L. Blood samples were incubated in an
      amino acid mixture containing [3H]leucine and chromatographed allowing the
      separation and quantitation of the alpha, beta, and gamma (A gamma T, G gamma,
      and A gamma I) chains. Erythropoietin was determined by RIA. The mean HbF
      synthesis was 77.9 +/- 8.9% of total Hb synthesis (range: 61 to 91%). Plasma
      erythropoietin concentrations were 21.4 +/- 6.4 mU/mL. There was no correlation
      between the total Hb or HbF synthesis and the level of erythropoietin. There was,
      however, a significant inverse correlation between the Hb level and HbF synthesis
      (p < 0.01). Nine infants who had received transfusions during the first few days
      of life had a mean HbF that was 53.5 +/- 15.2% of total Hb, whereas their HbF
      synthesis was 78.4 +/- 7.6%. Four of the infants never received transfusions; the
      total circulating HbF and HbF synthesis in these infants were 87.7 +/- 7.7% and
      76.8 +/- 12.7%, respectively. This study shows that there can be a reactivation
      of HbF synthesis during severe anemia of prematurity.

PMID- 7526325
TI  - Maternal hypoxia as a model for intrauterine growth retardation: effects on
      insulin-like growth factors and their binding proteins.
AB  - Evidence suggests that IGF and their binding proteins play a role in fetal
      growth, but more knowledge concerning their regulation is essential. We examined
      the expression of IGF and their binding proteins in experimental intrauterine
      growth-retarded (IUGR) rat fetuses of hypoxic dams (13-14% oxygen, d 14-21 of
      gestation). The mean body weight of the fetuses (d 21 of gestation, n = 72) of
      the six hypoxic dams was 24% lower (p < 0.0001) than the mean weight of the
      fetuses of six control dams (n = 82). Wet liver weights demonstrated a 20%
      decrease (p < 0.0001) and placentas a 10% decrease (p < 0.01) compared with
      control fetuses. The mean serum concentrations of immunoreactive IGF-I in both
      groups were low but did not differ significantly. The mean serum concentrations
      of immunoreactive IGF-II, however, were higher in IUGR fetuses. As assessed by
      Northern blot analysis, there was a 4-fold increase in insulin-like growth factor
      binding protein-1 (IGFBP-1) mRNA expression in the livers of the IUGR fetuses
      compared with controls. IGFBP-2 mRNA expression was 6-fold increased in IUGR
      fetal livers. No difference was found in IGFBP-4 mRNA. An increase in IGFBP-1, 
      2, and -4 concentrations could be seen by Western ligand blotting in the serum of
      growth-retarded fetuses compared with control fetuses. This finding was verified
      by immunoprecipitation with specific antibodies, which demonstrated increases in
      IGFBP-1 and IGFBP-2. Our results validate the use of maternal hypoxia as an
      experimental model of intrauterine growth retardation and indicate that increased
      IGFBP-1 and -2 expression may be of importance in the etiology of fetal growth
      retardation caused by maternal hypoxia.

PMID- 7526327
TI  - Fever, back pain and pleural effusion in a four-year-old boy.

PMID- 7526328
TI  - Inapparent transmission of Pseudomonas (Burkholderia) cepacia among patients with
      cystic fibrosis.
AB  - Pseudomonas cepacia is a significant pathogen in children and young adults with
      cystic fibrosis, and prevention of its acquisition has become an important goal
      in patient management. Although it is now clear that this bacterium can be
      transmitted from person to person, the frequency of this mode of acquisition and
      the measures required to prevent it are controversial. In this report we describe
      the use of a novel genotyping method to extend our previous investigation of
      person to person transmission of P. cepacia among patients with cystic fibrosis
      attending an educational program. Three (20%) of 15 individuals acquired P.
      cepacia after contact with a chronically colonized patient. Analysis revealed
      that the isolates recovered from the three newly colonized patients were the same
      as that from the index patient. We also demonstrated that pulmonary colonization
      with P. cepacia may not be detected by currently recommended culture methods for
      as long as 2 years after acquisition. These data indicate a need to develop more
      sensitive means of detecting P. cepacia colonization in order better to
      understand host-pathogen interaction and to optimize preventive strategies.

PMID- 7526329
TI  - Developmental and service needs of school-age children with human
      immunodeficiency virus infection: a descriptive study.
AB  - OBJECTIVE: To describe the developmental functioning and service needs of a group
      of school-age children with human immunodeficiency virus (HIV) infection. DESIGN:
      Retrospective data were collected through chart reviews and follow-up telephone
      calls to primary care givers. SETTING: A multidisciplinary team provided care at
      a developmental diagnostic and treatment center. PATIENTS: Cases were 90 school
      age children (ages 5 to 14 years) with presumed perinatally acquired HIV
      infection. RESULTS: Forty-four percent of the 86 children on whom there were
      diagnoses were functioning in the low average to average range of intelligence,
      whereas 56% were functioning in the borderline range or lower. Fifty percent of
      the children demonstrated significant language impairments, with 28% also
      demonstrating an articulation disorder. Thirty-six of the children (42%) were
      formally diagnosed as having emotional/behavioral disorders. Eighty-six of the
      children were in school-based programs and of that group, 74% were in special
      education classes and receiving related services. CONCLUSIONS: Most of the
      children in this study demonstrated deficits in the cognitive and learning areas,
      although they are clearly functioning better than earlier studies of children
      with HIV infection would have predicted. Their service needs include alternative
      living arrangements, remedial education, and psychotherapeutic interventions. The
      children's increasing longevity will place strains on the respective service
      systems.

PMID- 7526330
TI  - Which children benefit the most from early intervention?
AB  - Recent findings from three separate studies support and extend a large and
      growing body of early-intervention research literature spanning 30 years. The
      literature is consistent in demonstrating positive developmental outcomes as a
      result of intensive early intervention for children of low-income and
      undereducated families. New analyses confirm that maternal intelligence is a key
      factor in children's intellectual development, especially when these children are
      not provided with intensive early intervention. Fortunately, children whose
      mothers have low IQs respond positively to intensive, high-quality early
      intervention, which leads to a dramatic reduction in their rates of mental
      retardation during the intervention program. Unresolved issues include how best
      routinely to identify children and families who will benefit from such programs,
      how early to begin programs and for how long to continue them to produce
      desirable developmental outcomes, and whether sufficient public and political
      will exists to scale-up early intervention efforts to match the magnitude of the
      problem in our society.

PMID- 7526331
TI  - Actions of growth-hormone-releasing hormone on rat pituitary cells: intracellular
      calcium and ionic currents.
AB  - Actions of growth-hormone-releasing hormone (GHRH) on single rat anterior
      pituitary cells were studied using indo-1 fluorescence to monitor changes in
      intracellular calcium, [Ca2+]i, and perforated-patch recording to measure changes
      in membrane potential and ionic currents. GHRH elevated [Ca2+]i in non-voltage
      clamped cells by a mechanism that was dependent upon extracellular Na+ and Ca2+
      and was blocked by the dihydropyridine Ca(2+)-channel blocker, nitrendipine.
      Resting cells had a fluctuating membrane potential whose a mean value depolarized
      by 9 mV in response to GHRH. The membrane-permeant cAMP analogue, 8-(4
      chlorophenylthio)cAMP, mimicked the action of GHRH on membrane potential. Under
      voltage clamping, GHRH activated a small inward current (1-5 pA). Two types of
      response could be distinguished. The type I response had an inward current that
      was largest at more negative potentials (-90 mV), and the type II response had
      inward current that was larger at more positive potentials (-40 to -70 mV). Both
      types of response were reversible and blocked by removal of extracellular Na+.
      These results suggest that the rise in [Ca2+]i produced by GHRH in non-voltage
      clamped cells results from the activation via cAMP of a Na(+)-dependent
      conductance, which depolarizes the cell and increases the Ca2+ influx through
      voltage-gated Ca2+ channels.

PMID- 7526332
TI  - Voltage- and time-dependent block of I(f) by Sr2+ in rabbit sino-atrial node
      cells.
AB  - The hyperpolarization-activated cation current (I(f)) was recorded in single
      myocytes dissociated from the rabbit sino-atrial node and the Sr(2+)-mediated
      block of I(f) examined. In the presence of 0.1-10 mM Sr2+, the activation phase
      of I(f) was followed by a slower decay during hyperpolarization. In the steady
      state I/V diagram, the Sr2+ block progressed with increasing hyperpolarization.
      Ba2+ also blocked I(f), but no time dependency could be observed. The blocking
      effect of Ca2+ was weak, and Mg2+ had little effect on I(f). The relationship
      between extracellular Sr2+ concentration [Sr2+]o and the block was described by a
      Hill coefficient of 1. The half-saturating [Sr2+]o were 2.0, 1.6, 1.1 and 0.65 mM
      at -90, -100, -110 and -120 mV, respectively. The rapid application of Sr2+
      during the full activation of I(f) using the jet-stream method induced an
      exponential decline of I(f). The reciprocal time constants were linearly
      correlated to [Sr2+]o, suggesting 1:1 binding stoichiometry. The fractional
      electrical distance for the binding site was approximately 0.5 from the external
      side of the channel. Based on the multiple closed and open states for the I(f)
      channel, a mathematical model for the Sr2+ block was constructed in which the
      time course of I(f) in the presence of Sr2+ was described by the sum of three
      exponential functions. Fitting the model to the original traces revealed blocking
      and unblocking rates similar to those obtained from the jet-stream method. At 
      110 mV, the blocking rate was 410 M-1 s-1 while the unblocking rate was 0.16 s
      1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526333
TI  - Spontaneous transient inward currents and rhythmicity in canine and guinea-pig
      tracheal smooth muscle cells.
AB  - Spontaneous transient inward currents (STICs) were recorded in canine and guinea
      pig tracheal myocytes held at negative membrane potentials. STICs were Cl-
      selective since their reversal potential was dependent on the Cl- gradient and
      they were blocked by the Cl- channel blocker niflumic acid. STICs were
      insensitive to Cs+, charybdotoxin, and nifedipine. Ca(2+)-activated K+ currents
      often preceded STICs, suggesting that the STICs are Ca2+ dependent. In support of
      this suggestion, we found the Cl- currents were: (1) abolished by depleting
      intracellular Ca2+ stores using caffeine, acetylcholine, histamine, or substance
      P; (2) enhanced by increasing external concentrations of Ca2+; (3) evoked by
      voltage-dependent Ca2+ influx. The channels responsible for this Cl- current are
      of small unitary conductance (< 20 pS). Decay of the STICs was described by a
      single exponential with a time constant of 94 +/- 9 ms at -70 mV; the time
      constant increased considerably at more positive potentials. Using Ca(2+)
      dependent Cl- currents and contractions as indices of internal levels of Ca2+, we
      found that isolated tracheal cells are capable of exhibiting rhythmic behaviour:
      bursts of currents and contractions with a periodicity of less than 0.1 Hz and
      which continued for more than 20 min. These rhythmic events were recorded at
      negative membrane potentials, suggesting that cyclical release of internally
      sequestered Ca2+ is responsible. We conclude that spontaneous release of Ca2+
      from intracellular stores in tracheal muscle cells leads to transient currents in
      some cases accompanied by rhythmic contractions. Our studies provide evidence for
      a cellular mechanism that could underly myogenic oscillations of membrane
      potential in smooth muscle.

PMID- 7526335
TI  - Effect of acetyl choline on ion transport in sheep tracheal epithelium.
AB  - The action of acetylcholine (ACh) on sheep tracheal epithelium has been
      investigated. ACh increases transiently the short-circuit current (ISC). The same
      response is obtained in tissues in which the apical membrane has been
      permeabilized with amphotericin B in the presence of a potassium gradient.
      Microelectrode studies show that the majority of tracheal epithelial cells
      depolarize as the apical fractional resistance decreases on application of ACh.
      These results, together with the finding that bumetanide decreases the initial
      ACh-induced ISC increase, are consistent with an initial activation by ACh of
      apical Cl- channels and basolateral K+ channels. Following the initial increase,
      ISC declines to values lower than in control conditions both in untreated and in
      amphotericin-permeabilized tissues, suggesting that the basolateral K+
      conductance falls during this phase. The late decrease in ISC induced by ACh is
      significantly reduced in tissues pretreated with amiloride, suggesting that the
      apical Na+ channels are also involved in this response. ACh abolishes the net Na+
      absorption by decreasing the mucosal to serosal Na+ flux. This effect is possibly
      a result of a down-regulation of apical Na+ channels and basolateral K+ channels.

PMID- 7526334
TI  - Facilitation by 5-hydroxytryptamine of ATP-activated current in rat
      pheochromocytoma cells.
AB  - The effects of 5-hydroxytryptamine (5-HT) on an inward current activated by
      extracellular ATP were investigated in rat pheochromocytoma PC12 cells. Under
      whole-cell voltage-clamp conditions 5-HT (10 microM) reversibly enhanced the
      amplitude of the current activated by 30 microM ATP. The enhancement may not be
      due to an increase in the number of functional channels because the current
      activated by 300 microM ATP was not remarkably augmented compared with the
      current activated by 30 microM ATP. The current enhancement by 100 microM 5-HT
      was less obvious than that by 10 microM 5-HT. When the current kinetics were
      compared, activation of the ATP-evoked current was accelerated to the same extent
      by either 10 or 100 microM 5-HT, whereas deactivation was largely more
      accelerated by 100 microM 5-HT. Propranolol (10 microM), a 5-HT1 receptor
      antagonist, or LY53857 (10 microM), a 5-HT2 receptor antagonist, exerted an
      agonistic effect: the ATP-activated current was facilitated by these compounds.
      Metoclopramide (10 microM), a 5-HT3 receptor antagonist, neither facilitated the
      ATP-activated current, nor blocked the current facilitation by 5-HT. Guanosine 5'
      O-(2-thiodiphosphate) (GDP[beta S]) (2 mM), the non-hydrolysable analog of
      guanosine 5'-triphosphate (GTP), or K-252a (2 microM), a protein kinase
      inhibitor, did not affect the facilitation by 5-HT of the ATP-activated current
      when they were included in the intracellular solution. The ATP-activated current
      pre-facilitated by 10 microM dopamine was not enhanced by 10 microM 5-HT.
      Similarly, the pre-facilitation by 5-HT attenuated the current enhancement by
      dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526336
TI  - Cell swelling activates a poorly selective monovalent cation channel in the
      apical membrane of toad urinary bladder.
AB  - We measured the effects of conditions that increase cell volume on ion movements
      through the Ca(2+)-blockable poorly selective monovalent cation channel of the
      apical membrane of the toad urinary bladder. Three conditions were studied:
      dilution of the basolateral solution, basolateral perfusion with solutions
      prepared with solutes of low reflection coefficient and dilution of the apical
      solution in bladders treated with oxytocin. All three procedures markedly
      increased K+ movements and elevated the plateau of the Lorentzian component of
      the power spectrum by enhancing ion currents through the Ca(2+)-blockable
      pathway. Simultaneously there was a large increase in Ca(2+)-sensitive
      conductance. The magnitude of this increased conductance strongly suggests that
      the stimulation of ion flow is due to increased ion permeability and not solely
      to increases in driving force across the apical membrane. We were not able to
      detect an increase in the movements of alkali-earth ions induced by the
      conditions that increase cell volume. We speculate that activation of the Ca(2+)
      blockable channel may play an important role in the regulation of cell volume
      and/or in K+ homeostasis.

PMID- 7526338
TI  - Forskolin and PMA pretreatment of HT29 cells alters their chloride conductance
      induced by cAMP, Ca2+ and hypotonic cell swelling.
AB  - HT29 cells were preincubated with forskolin (10(-5) mol/l, FORHT) or phorbol 12
      myristate 13-acetate (PMA) (10(-7) mol/l, PMAHT) for 20 h, which has been shown
      previously and is also shown here, to upregulate and downregulate, respectively,
      the expression of the cystic fibrosis transmembrane conductance regulator (CFTR).
      CFPAC-1 cells underwent the same protocols. HT29 cells were examined by slow
      (SWC) and fast (FWC) whole-cell patch-clamp techniques. The results of SWC and
      FWC were indistinguishable and were pooled. CFPAC-1 cells were examined with FWC.
      The membrane voltage (V) of FORHT was -41.8 +/- 1.4 mV (n = 77) and that of PMAHT
      was -43.6 +/- 2.4 mV (n = 76). The conductance (G) of FORHT (9.4 +/- 0.9 nS, n =
      77) was significantly larger than that of PMAHT (3.7 +/- 0.4 nS, n = 76). Acute
      application of forskolin (10(-5) mol/l, FOR) plus 0.5 mmol/l 8-(4
      chlorophenylthio)-cAMP (cAMP) depolarized V by 12 (FORHT) and 8 (PMAHT) mV,
      respectively. The acute increase of G by FOR plus cAMP was by 7.6 +/- 1.9 nS for
      FORHT (n = 22) and only 2.2 +/- 1 nS for PMAHT (n = 13). ATP (10(-4) mol/l)
      depolarized V in both types of cells. It enhanced G by 16.7 +/- 4.1 nS in FORHT
      (n = 14) and significantly less (by 5.5 +/- 1.2 nS, n = 14) in PMAHT. Also the G
      increase lasted longer in FORHT. Neurotensin (NT, 10(-8) mol/l) also had a
      stronger and longer lasting effect in FORHT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526337
TI  - Volume regulatory responses in frog isolated proximal cells.
AB  - Cells respond to increase in volume by activating solute efflux pathways,
      resulting in water loss and restoration of the original cell volume. The solute
      efflux pathways underlying these volume regulatory decrease (VRD) responses have
      been relatively well studied. However, the transduction pathways whereby the
      change in cell volume is converted into an intracellular signal resulting in VRD
      are much less well understood. We have examined VRD in isolated proximal tubule
      cells from the frog, with particular attention to the roles of stretch-activated
      channels, Ca2+ and protein kinases. Cell length was taken as an index of cell
      volume, and was measured continuously using a photodiode array. VRD was observed
      in approximately 50% of cells, and was inhibited by Ba2+, Gd3+ and 4,4'
      diisothiocyanatostilbene 2,2'-disulphonic acid (DIDS), and removal of
      extracellular Ca2+. VRD was accelerated by the active phorbol ester, phorbol 12
      myristate 13-acetate (PMA), and the phosphatase inhibitor F-; on the other hand,
      VRD was prolonged by 4 alpha-phorbol 12,13-didecanoate (PDC), an inactive phorbol
      ester), and inhibited by PMA and Gd3+, PMA and 0 Ca2+, and staurosporine. Volume
      regulation was unaffected by di-butyryl cAMP and 3-isobutyl-1-methyl-xanthene
      (IBMX). These data suggest that Ca2+ and PKC, via protein phosphorylation, play a
      stimulatory role in VRD.

PMID- 7526340
TI  - [Selection for a hospice--a multi-faceted task].
AB  - The object with this article is to pass on experience regarding the registration
      of patients for admittance to Sankt Lukas Stiftelsens Hospice in Denmark. It is a
      large and difficult ethical problem, in how far one can accept a more or less
      unsure diagnosis in connection with admittance to a hospice, either because it
      has not been medically possible to reach, or because the patient is unable to
      accept a precise diagnosis. It can be difficult for the patient to drop curative
      treatment, and by doing so indirectly choose purely palliative treatment. The
      admittance staff of the hospice have a large responsibility. They should ensure,
      that patients and their relatives are fully informed of, what the hospice can
      offer, and especially what it cannot offer in the way of curative medicine. One
      must prefer, that patients qualified for admittance to the hospice are competent
      during the admittance stage. It would in many cases be troubling and difficult
      after duly supported assumptions to accept patients with non-malign diseases for
      admittance to the hospice.

PMID- 7526339
TI  - Protein kinase A increases availability of calcium channels in smooth muscle
      cells from guinea pig basilar artery.
AB  - We studied single Ca2+ channels in smooth muscle cells from the basilar artery of
      the guinea pig using conventional patch-clamp techniques. With 40 mM or 90 mM
      Ba2+ as the charge carrier, a 23-pS inward current channel was observed in 46/187
      cell-attached patches studied without the dihydropyridine, BAY K8644, in the
      pipette solution. At 0 mV, this channel exhibited short and long openings with
      time constants of 1.03 and 3.65 ms, respectively. The probability of channel
      opening was voltage dependent with half-activation occurring at +9.9 mV. In 14/26
      patches tested, addition of 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP) to
      the bath increased the probability of opening at -10 mV by a factor of 2.6, from
      0.0272 +/- 0.0429 to 0.0695 +/- 0.0788 (P < 0.01, paired t-test). Mean data from
      five patches fit to a Boltzmann function indicated that at positive potentials,
      the probability of opening increased by a factor of 1.7, from 0.352 to 0.600,
      whereas the voltage dependence, the number of channels, the number of open
      states, the time constants of the open states, and the proportion of time spent
      in each open state were unchanged. When BAY K8644 was added to the pipette
      solution, the 23-pS channel was observed in nearly all patches (62/66), but the
      voltage dependence of activation was shifted -15.3 mV compared to control. In
      some patches studied with 90 mM Ba2+, a 9-pS inward current channel also was
      observed and its activity also was increased significantly by 8-Br-cAMP.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7526341
TI  - Interactions among regulators of RNA abundance characterized using RNA
      fingerprinting by arbitrarily primed PCR.
AB  - Using RNA fingerprinting by arbitrarily primed PCR it is possible to infer
      convergent transcript regulatory pathways from the coordinate behavior of subsets
      of anonymous transcripts without cloning any genes. The number of transcripts in
      each response category can be estimated. The same may be true for differential
      display. We demonstrate these claims by treating a cell line with two known
      modulators of RNA abundance, transforming growth factor-beta (TGF beta) and
      cycloheximide (CX), used together and alone. The responses of over 1700 anonymous
      transcripts were monitored under these three conditions and in an untreated
      control. Eight of the twenty-seven [3(3)] possible transcript response categories
      were observed among 86 differentially expressed transcripts. For example, CX
      stabilizes or induces as many as 2.7% of transcripts of which about one third do
      not accumulate when TGF beta is also present. This intersection may reflect CX
      stabilization or induction of an important class of RNAs that otherwise usually
      have short half-lives. We predict that RNAs in this class constitute the majority
      of transcripts targeted for rapid down regulation in response to TGF beta and
      perhaps most other natural transcriptional modulators.

PMID- 7526342
TI  - Transfer of a constitutive viral promoter-cystic fibrosis transmembrane
      conductance regulator cDNA to human epithelial cells conveys resistance to down
      regulation of cAMP-regulated Cl- secretion in the presence of inflammatory
      stimuli.
AB  - The expression of the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene can be down-regulated by inflammatory stimuli such as phorbol myristate
      acetate (PMA). Since the respiratory manifestations of cystic fibrosis (CF) are
      characterized by intense chronic airway inflammation very early in life,
      successful gene therapy for CF will require that expression of the transferred
      normal CFTR gene be resistant to down-regulation by inflammatory mediators. To
      evaluate the concept that a viral promoter--human CFTR cDNA unit would be
      resistant to this form of down-regulation, a retrovirus promoter (5' long
      terminal repeat of the Moloney murine leukemia virus)--human CFTR cDNA unit was
      transferred to T84 human colon carcinoma cell line using a retrovirus vector.
      Exposure of the retrovirus-modified T84 cells to PMA resulted in down-regulation
      of the endogenous CFTR mRNA transcripts (6.5 kb), but did not affect the level of
      exogenous CFTR transcripts (8.0 kb). Importantly, in parallel with the
      persistence of the exogenous CFTR transcripts, the modified cells still
      maintained cAMP-regulated CI- secretion in the presence of PMA. These in vitro
      data suggest that a constitutive viral promoter--CFTR cDNA unit should be
      resistant to modulation by inflammatory stimuli, a likely requirement for
      successful gene therapy for CF.

PMID- 7526343
TI  - Interactions of oligonucleotide analogs containing methylphosphonate
      internucleotide linkages and 2'-O-methylribonucleosides.
AB  - The interactions of oligonucleotide analogs, 12-mers, which contain deoxyribo- or
      2'-O-methylribose sugars and methylphosphonate internucleotide linkages with
      complementary 12-mer DNA and RNA targets and the effect of chirality of the
      methylphosphonate linkage on oligomer-target interactions was studied. Oligomers
      containing a single Rp or Sp methylphosphonate linkage (type 1) or oligomers
      containing a single phosphodiester linkage at the 5'-end followed by 10
      contiguous methylphosphonate linkages of random chirality (type 2) were prepared.
      The deoxyribo- and 2'-O-methylribo- type 1 12-mers formed stable duplexes with
      both the RNA and DNA as determined by UV melting experiments. The melting
      temperatures, Tms, of the 2'-O-methylribo-12-mer/RNA duplexes (49-53 degrees C)
      were higher than those of the deoxyribo-12mer/RNA duplexes (31-36 degrees C). The
      Tms of the duplexes formed by the Rp isomers of these oligomers were
      approximately 3-5 degrees C higher than those formed by the corresponding Sp
      isomers. The deoxyribo type 2 12-mer formed a stable duplex, Tm 34 degrees C,
      with the DNA target and a much less stable duplex with the RNA target, Tm < 5
      degrees C. In contrast, the 2'-O-methylribo type 2 12-mer formed a stable duplex
      with the RNA target, Tm 20 degrees C, and a duplex of lower stability with the
      DNA target, Tm < 5 degrees C. These results show that the previously observed
      greater stability of oligo-2'-O-methylribonucleotide/RNA duplexes versus
      oligodeoxyribonucleotide/RNA duplexes extends to oligomers containing
      methylphosphonate linkages and that the configuration of the methylphosphonate
      linkage strongly influences the stability of the duplexes.

PMID- 7526344
TI  - High-density multiplex detection of nucleic acid sequences: oligonucleotide
      ligation assay and sequence-coded separation.
AB  - We describe a non-isotopic, semi-automated method for large-scale multiplex
      analysis of nucleic acid sequences, using the cystic fibrosis transmembrane
      regulator (CFTR) gene as an example. Products of a multiplex oligonucleotide
      ligation assay (OLA) are resolved electrophoretically from one another and from
      unligated probes under denaturing conditions with fluorescence detection. One
      ligation probe for each OLA target carries a fluorescent tag, while the other
      probe carries an oligomeric non-nucleotide mobility modifier. Each OLA product
      has a unique electrophoretic mobility determined by the ligated oligonucleotides
      and the mobility-modifier oligomer arbitrarily assigned (coded) to its target.
      The mobility range for practical mobility modifiers is much wider than the
      accessible range from unmodified ligated oligonucleotides of practical length.
      Each mobility modifier is built from phosphoramidite monomers in a stepwise
      manner on its associated oligonucleotide using an automated synthesizer. The
      resulting mobility modifiers lower the probe-target duplex Tm by less than 3
      degrees C and retard probe-target annealing by less than 50%, with negligible
      effect on OLA yield and specificity. This method is especially useful for allelic
      discrimination in highly polymorphic genes such as CFTR.

PMID- 7526346
TI  - Last chance to care.

PMID- 7526345
TI  - A rapid procedure for the quantitation of low abundance RNAs by competitive
      reverse transcription-polymerase chain reaction.

PMID- 7526347
TI  - Caring for a patient with oral cancer needing surgery.
AB  - This paper describes the care of a man following unsuccessful surgery for oral
      cancer. The authors describe the way in which the patient was involved in
      decision-making about his care and how this contributed to the maintenance of
      dignity and self-respect in the months before his death.

PMID- 7526348
TI  - A new method for diagramming pacemaker electrocardiograms.
AB  - Advancements in technology have made paced ECG interpretation increasingly
      difficult. A new method for depicting the complex pacemaker/heart interactions
      that eliminates the extensive use of symbols and repetitious use of refractory
      period and rate limit information of previous methods has been devised. The
      method uses a framework of parallel horizontal lines drawn on grid paper
      underneath the ECG. The lines are spaced apart by the actual programmed values
      (lower rate, AV, VA intervals) of the pacemaker in question. This framework
      allows the simultaneous use of the horizontal and vertical directions for the
      diagram of pacemaker timing intervals. Also, a single representation of
      refractory periods, upper rate intervals, and other variables can be labeled
      vertically and extrapolated horizontally across the entire diagram. Single
      chamber, dual chamber, and rate-modulated ECGs are readily represented. The
      diagram is easily plotted on standard ECG paper and flexible enough to represent
      complex ECGs.

PMID- 7526349
TI  - Idiopathic ventricular fibrillation in out-of-hospital cardiac arrest survivors.
AB  - This study examined diagnostic and therapeutic roles of electrophysiological
      testing and long-term clinical outcome after out-of-hospital cardiac arrest due
      to idiopathic ventricular fibrillation. This is defined as ventricular
      fibrillation occurring in the absence of detectable underlying heart disease or
      metabolic or electrolyte disturbance. Out-of-hospital cardiac arrest resulting
      from idiopathic ventricular fibrillation is uncommon. Records of all patients who
      underwent electrophysiological testing between June 1979 and June 1992 were
      reviewed. Patients with out-of-hospital cardiac arrest due to idiopathic
      ventricular fibrillation were identified. Follow-up information was obtained by
      telephone interview in June 1992. Of 194 patients who underwent
      electrophysiological study after out-of-hospital cardiac arrest not associated
      with acute myocardial infarction, only six (4 male and 2 female) had idiopathic
      ventricular fibrillation. It was induced in only two patients by programmed
      ventricular stimulation. No sustained ventricular arrhythmias were induced in the
      remaining four patients. Four patients received implantable cardioverter
      defibrillators, one was treated with a beta-adrenergic blocker, and one received
      no treatment. All patients were alive at a mean follow-up of 50 months. Two of
      the four patients without inducible sustained ventricular arrhythmias had events
      during follow-up. Of the two patients with inducible ventricular fibrillation,
      one experienced a cardiac arrest and documented ventricular fibrillation at 41
      months after the index event and the other had had no recurrence at 15-month
      follow-up. All four patients with implantable cardioverter defibrillators were
      alive at last follow-up, and two had device discharges.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7526350
TI  - Tending the spirit.

PMID- 7526352
TI  - Bone alkaline phosphatase and prostate-specific antigen in the monitoring of
      prostate cancer.
AB  - A retrospective study has been made on the interrelationship of serum bone
      alkaline phosphatase (BAP), measured by the Ostase-RIA, and prostate-specific
      antigen (PSA) in 156 patients with M0 and M1 prostate cancer. BAP is a more
      sensitive and more specific method of determining osteoblast activity than total
      alkaline phosphatase (TAP). The main difference between these two assays is seen
      when the TAP is in the range of normal to twice-normal. BAP shows a low
      intraindividual variation in M0 disease, and was within normal limits in 18
      patients following radical prostatectomy with a PSA < 0.1 ng/ml. A raised BAP was
      observed in 86.4% of M1 disease at diagnosis before treatment. The change of BAP
      was concordant with PSA in 69% of 49 cases of M1 disease, although there are
      marked differences in the rates of change of the two markers. A nadir of PSA < or
      = 10 ng/ml after androgen blockade in M1 disease was associated with a high
      probability of a normal BAP.

PMID- 7526351
TI  - [High-dose chemotherapy, G-CSF and the use of peripheral blood progenitor cells
      in patients with poor-prognosis neuroblastoma].
AB  - In the past decade there has been an increasing use of high dose of chemo
      radiotherapy in the treatment of poor prognosis solid tumors of childhood. The
      autologous bone marrow transplantation is the most used technique for
      circumventing the infectious and haemorrhagic complications occurring in the
      prolonged period of myelotoxicity. The faster recovery assured by the peripheral
      blood progenitor cells (PBPC) makes this procedure an attractive alternative. The
      advent of new apheretic modalities and the use of combinations of active
      antineoplastic drugs with various growth factors, such as G-CSF, GM-CSF and IL-3,
      has allowed to collect and concentrate the mononuclear fraction of peripheral
      blood leukocytes. The optimal timing for the collection is a crucial point and
      the utilization of flow cytometry for the determinations of circulating CD34+
      cells in the peripheral blood is so far the best indicator for successful
      apheresis. The authors describe their experience in 16 children affected by poor
      prognosis neuroblastoma who had undergone high dose chemotherapy followed by G
      CSF administration and PBPC collection. The details of apheretic techniques and
      the characteristics of conditioning regimen and haematologic recovery after PBPC
      reinfusion are also presented.

PMID- 7526354
TI  - Congenital sensory neuropathy with anhidrosis.
AB  - A 6-year-old girl had congenital sensory neuropathy with anhidrosis (CSNA), one
      of the five variants of a group of very rare genetic disorders of the peripheral
      nervous system--hereditary sensory neuropathies (HSN). Clinical, laboratory, and
      physiopathologic aspects are discussed. Dermatologic findings of anhidrosis and
      self-mutilation suggest the diagnosis.

PMID- 7526353
TI  - Fresh tissue harvest for research from prostatectomy specimens.
AB  - As a consequence of molecular biological and genetic techniques, the demand for
      fresh tissue for basic research has increased dramatically at academic medical
      centers. Because of the extreme lability of many biological macromolecules,
      tissue must be harvested with the least possible delay from the time of removal.
      This necessity for quick action, frequently under less than optimal
      circumstances, along with the obvious loss of tissue available for diagnostic
      purposes, presents a daunting challenge to the pathologist responsible for
      accurate grading and staging of the cancer. A novel approach is described for the
      procurement of fresh and freshly frozen prostatic tissue with acceptable
      limitations on subsequent morphological analysis.

PMID- 7526355
TI  - Cutaneous mucinosis of infancy.
AB  - Cutaneous mucinosis of infancy has been reported only rarely in the literature.
      We describe a case occurring in a black infant girl. Although no associated
      abnormalities have been described previously, our patient had a history of
      developmental delay, congenital cataracts, bilateral inguinal hernias, and an
      accessory tragus. The significance of these features is unclear.

PMID- 7526356
TI  - Solitary mastocytoma with massive eosinophilic infiltration.
AB  - An 11-month-old girl had a yellowish brown nodule that histologically had an
      unexpectedly massive infiltrate of eosinophils in the dermis. This histologic
      feature made determining the correct diagnosis of cutaneous solitary mastocytoma
      difficult until we performed specific histochemical staining for mast cells.

PMID- 7526358
TI  - [Immunologic processes in human placenta and their role in antiviral resistance.
      I. Virus infections of the uterus. Nonspecific antiviral immunity].
AB  - This paper deals with the viral infections of the fetus and properties of the
      human placenta acting as an immunological and anatomic barrier. Natural immunity,
      discussed in this chapter, regards to two principal mechanisms of immunity
      against viruses: production of IFN and natural cytotoxicity.

PMID- 7526357
TI  - Expression of insulin-like growth factor binding protein 2 (IGFBP-2) in Wilms'
      tumors.
AB  - Human Wilms' tumor (WT) expresses insulin-like growth factor (IGF) II and its
      cognate receptor, type 1 IGF receptor, forming a self-stimulating "autocrine
      loop." The biological activity of IGF-II is modulated by a class of soluble
      receptors called IGF binding proteins (IGFBP). To determine if IGFBP play a role
      in the biology of WT, extracts of nude mouse heterotransplants of three blastemal
      WT were examined for the ability to bind radiolabeled IGF-II by ligand blot
      analysis. [125I]IGF-II bound to a protein of M(r) 35 kDa. To confirm that this
      binding protein was being expressed by the tumor itself and not background from
      the host, tumor explants were prepared in cell culture. Conditioned culture media
      from blastemal WT cell cultures were found to contain the 35-kDa IGFBP. This
      secreted binding protein was identified as IGFBP-2 by screening for reactivity to
      characterized IGFBP antisera. Total RNA from primary WT or WT cells in culture
      was examined for expression of IGFBP-2 mRNA using an RNase protection assay. All
      three WT expressed IGFBP-2 mRNA. These data suggest a role for IGFBP-2 in the IGF
      II-dependent growth of Wilms' tumor and in the developing kidney.

PMID- 7526359
TI  - Effect of combination of deoxypyridoxine with known anti-proliferative or
      immunosuppressive agents on lymphocyte serine hydroxymethyltransferase.
AB  - Measurements of serine hydroxymethyltransferase (SHMT) in resting lymphocyte
      cultures showed that the level of activity of this enzyme is very low. Under the
      influence of mitogenic stimuli serine hydroxymethyltransferase activity is
      induced 5-20-fold. Addition in the cultures of 4-deoxypyridoxine (dB6), a potent
      antagonist of vitamin B6 coenzymes, concurrently with the mitogen, inhibits the
      induction of SHMT. Separate addition in the cultures of four anti-proliferative
      (AP) and immunosuppressive (IMS) agents, namely actinomycin, cytarabine,
      asparaginase and cyclosporine, led to the following observations. (1) The AP and
      IMS agents produce a decrease in the mitogen-induced activity of SHMT. The higher
      the concentration of the AP/IMS compound, the greater the decrease of enzymatic
      activity. (2) When a AP/IMS agent is combined with dB6 its effect on SHMT is
      considerably greater. (3) Ineffective concentrations of AP/IMS agents become
      effective when combined with dB6. (4) The observed changes in SHMT activity are
      not, as one would expect, the same in the case of all four drugs. (5) The
      combination makes it possible to use much smaller doses of these agents with much
      better results, at least as far as the decrease of enzymic activity is concerned.
      This is very promising for clinical use of AP agents in cancer chemotherapy and
      IMS agents in transplantation especially of the heart and lungs, because
      combining these compounds with dB6 will make possible to use smaller doses over a
      longer period of time with greater effectiveness.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7526360
TI  - Dose and regimen effects of poly ICLC, an interferon inducer, in a multi-dose
      bleomycin model of interstitial pulmonary fibrosis.
AB  - The antifibrotic effects of an interferon inducer, polyinosinic-polycytidylic
      acid complexed with poly-L-lysine (poly ICLC), was evaluated in a bleomycin
      hamster model of pulmonary fibrosis. Hamsters received three consecutive
      intratracheal doses of bleomycin (2.5, 2.0, and 1.5 U/kg/5 ml) or saline at
      weekly intervals. Poly ICLC at three doses (0.5, 1.0, and 1.5 mg/kg body weight)
      or saline was injected intraperitoneally by daily and semiweekly regimens for
      four weeks, and animals were sacrificed at five weeks. In both the daily and
      semiweekly poly ICLC regimens, hamsters receiving bleomycin plus poly ICLC
      demonstrated increased mortality and decreased weight gain compared to the
      vehicle and bleomycin control groups. The groups receiving bleomycin plus daily
      poly ICLC demonstrated poly ICLC-dose related effects for weight changes, lung
      hydroxyproline and lung prolyl hydroxylase activity. Depending on the poly ICLC
      dose, bleomycin plus daily poly ICLC produced significantly decreased
      hydroxyproline or significantly increased hydroxyproline and prolyl hydroxylase
      activity compared to the bleomycin control group. In contrast, the groups
      receiving bleomycin plus semiweekly poly ICLC did not demonstrate poly ICLC-dose
      related effects or significant differences from the bleomycin control group for
      any of the biochemical assays performed. The results of this study indicate that,
      depending on dose and regimen, poly ICLC can reduce collagen accumulation or
      produce a synergistic toxicity when administered with multiple doses of
      bleomycin. The toxic effects may restrict the therapeutic potential of poly ICLC
      in combination with bleomycin for anticancer therapy.

PMID- 7526361
TI  - Effect of toluene inhalation on extracellular striatal acetylcholine release
      studied with microdialysis.
AB  - Intracerebral microdialysis was performed on awake, freely moving rats in order
      to record effect of toluene exposure on acetylcholine release in striatum.
      Acetylcholine release decreased during (about 20%) and after (about 60%) toluene
      exposure (2 hr, 2000 p.p.m.) Striatal acetylcholine release is thought to be
      mediated by dopamine. In a previous work we found that extracellular dopamine
      levels increase during toluene exposure. A dopamine uptake inhibitor (LU 19-005,
      2 mg/kg) was therefore injected subcutaneously and the effect of increased
      extracellular dopamine on acetylcholine release within the striatum was monitored
      in the absence of toluene exposure. LU 19-005 increased striatal dopamine levels
      six times and the acetylcholine levels increased to about 145% of basal value.
      The present study shows that toluene exposure decrease acetylcholine release
      while an injection of a dopamine uptake inhibitor fails to decrease acetylcholine
      release. Indicating that acute exposure of toluene decreases striatal
      acetylcholine release by a mechanism that is not mediated by increased
      extracellular dopamine levels. Our data suggest that toluene decrease
      acetylcholine release within the striatum and that this effect not is mediated by
      increased extracellular dopamine levels.

PMID- 7526362
TI  - Incremental cost-effectiveness of incorporating oestriol evaluation in Down
      syndrome screening programmes.
AB  - As screening for Down syndrome becomes increasingly sophisticated, it is
      important to evaluate the newer technologies in terms of their cost
      effectiveness. One recent addition to Down syndrome screening programmes is
      maternal serum unconjugated oestriol (uE3), especially when used in conjunction
      with maternal serum alpha-fetoprotein and human chorionic gonadotropin. Using
      assumptions used in a California proposal to justify an expanded screening
      programme for Down syndrome, we calculated both the average and the incremental
      cost-effectiveness of adding uE3. Using the base case assumptions, including an
      $8 fee for the uE3, the incremental cost-effectiveness of adding uE3 to the
      proposed California programme is $119,100 per case detected, a value that
      compares favourably with other Down syndrome screening programmes. The
      sensitivity analysis supports this conclusion over a wide range of assumptions.
      However, because of the uncertainty with some key data, it is still too early to
      fully support the inclusion of uE3 in Down syndrome screening programmes.

PMID- 7526363
TI  - Down's syndrome screening in multiple pregnancies using alpha-fetoprotein and
      free beta hCG.
AB  - Second-trimester distributions of the free beta human chorionic gonadotrophin
      (hCG) and alpha-fetoprotein (AFP) levels in 420 twin and 19 triplet pregnancies
      were measured and compared with the distributions in 6661 singleton pregnancies.
      On average, the levels of both analytes were twice as high and over three times
      as high in triplets. Eight sets of twins discordant for Down's syndrome showed
      elevated levels of free beta hCG and reduced levels of AFP after correction of
      the multiple of the median for the presence of a twin pregnancy. Screening for
      Down's syndrome using the twin correction of the multiple of the median is
      expected to achieve a 51 per cent detection rate at a 5 per cent false-positive
      rate using these two markers.

PMID- 7526364
TI  - Maternal serum markers in second-trimester oligohydramnios.
AB  - The levels of the maternal serum markers alpha-fetoprotein (AFP), human chorionic
      gonadotrophin (hCG), and unconjugated oestriol (uE3) in 35 pregnant women with
      early second-trimester oligohydramnios differed from those in a reference
      population of 1699 singleton pregnancies. Maternal serum AFP levels above the
      95th centile of the population distribution were observed in 80 per cent (16/20)
      of oligohydramnios cases with a normal fetus and in only 20 per cent (3/15) of
      the cases with a fetus displaying urogenital tract malformations. Elevated levels
      of hCG (above the 95th centile) and decreased levels of uE3 (below the fifth
      centile) were encountered in 26 per cent (9/35) and 17 per cent (6/35) of the
      women, irrespective of the fetal condition. The abnormal profile of the serum
      markers in early second-trimester oligohydramnios resulted in 57 per cent (20 out
      of 35) of screen-positive cases for either fetal Down's syndrome or neural tube
      defects, compared with 8.4 per cent (143 out of 1699) in the reference
      population.

PMID- 7526365
TI  - Congenital nephrosis in low-risk pregnancies.
AB  - Congenital nephrosis is an autosomal recessive disorder requiring neonatal renal
      transplant for survival. The postnatal diagnosis rests upon the electron
      microscopic evaluation of the epithelial foot processes and basal membrane of the
      glomeruli. The prenatal diagnosis can be suspected in the presence of a positive
      family history with an amniotic fluid (AF) alpha-fetoprotein level greater than 5
      standard deviations (SD) above the population mean accompanied by a negative AF
      acetylcholinesterase, absent haemoglobin F, and an unremarkable fetal sonographic
      examination. We reviewed our series of seven cases of congenital nephrosis
      fulfilling the above criteria; four cases had negative family histories, and in
      two cases the diagnosis of congenital nephrosis was further supported by the
      presence of elevated AF albumin concentrations. We conclude that (1) the prenatal
      diagnosis of congenital nephrosis is feasible in a low-risk population, and (2)
      an elevated AF albumin concentration may represent an additional marker for the
      diagnosis of congenital nephrosis, even though false-negative results have been
      reported.

PMID- 7526366
TI  - Repeat maternal serum testing in multiple marker Down's syndrome screening
      programmes.
AB  - The effect of repeat testing in maternal serum multiple marker screening for
      Down's syndrome was estimated using samples stored in an antenatal serum bank.
      Human chorionic gonadotropin (hCG) and unconjugated oestriol (uE3) levels were
      determined in 142 pairs of routinely collected samples which had already been
      tested for alpha-fetoprotein (AFP). For each marker, about two-thirds of the
      pairs of values were within 20 per cent of each other and most were within 40 per
      cent. A multivariate Gaussian model was used to estimate the detection and false
      positive rates for different repeat testing policies. A policy of repeat testing
      those with a high risk of a Down's syndrome term pregnancy given age and marker
      levels would reduce the false-positive rate but there would also be a reduction
      in the detection rate. For example, using all three markers and a 1 in 250 cut
      off risk, the estimated false-positive rate would fall from 5.3 to 3.8 per cent
      but the detection rate would decrease from 58 to 55 per cent. A policy of
      repeating those with either high or borderline risks would produce a modest
      improvement in screening efficiency. Repeating the 11 per cent with a risk
      exceeding 1 in 500 yields an estimated false-positive rate of 5.0 per cent and a
      detection rate of 60 per cent. A policy of selective repeat testing is not
      recommended as it would not substantially improve screening efficiency.
      Nonetheless, if a repeat test has been performed, the parameters given in this
      paper will enable an unbiased estimate of the Down's syndrome risk to be
      calculated for individual women.

PMID- 7526367
TI  - Adverse perinatal outcome in patients screen-positive for neural tube defects and
      fetal Down syndrome.
AB  - An association between various abnormal mid-trimester maternal serum analyte
      values and adverse perinatal outcome has been reported. From an original sample
      of 14,857 women, we observed five women who were 'screen-positive' for both
      neural tube defects [maternal serum alpha-fetoprotein (MSAFP) > or = 2.5
      multiples of the median] and Down syndrome [risk > or = 1/274 using MSAFP,
      maternal serum unconjugated oestriol (MSuE3), maternal serum human chorionic
      gonadotropin (MShCG), and maternal age]. The four patients who elected to undergo
      amniocentesis all demonstrated both normal karyotype and normal amniotic fluid
      AFP levels. All five cases were associated with intrauterine growth retardation
      (IUGR) and abnormal pregnancy outcomes. Two cases exhibiting severe IUGR on
      ultrasound examination were terminated at 19.1 and 21.2 weeks, respectively; the
      former also exhibited fetal calcifications and positive maternal serology for
      toxoplasmosis. In another case, fetal demise occurred at 36 weeks' gestation in a
      patient who had been treated for syphilis in the second trimester. Neither
      infection was confirmed in fetal tissue studies. Though resulting in live births,
      the remaining two cases required operative deliveries; emergency Caesarean
      sections for fetal distress were performed at 38 and 32 weeks, respectively, the
      latter case being associated with severe pre-eclampsia. We conclude that elevated
      mid-trimester MSAFP levels concurrent with maternal serum analyte values
      associated with increased risk for fetal Down syndrome may presage a poor
      perinatal outcome, particularly IUGR and possibly congenital infection.

PMID- 7526368
TI  - Antenatal detection of neural tube defects: comparison of biochemical and
      immunofluorescence methods.
AB  - The aim of this study was to determine whether identification of glial cells in
      amniotic fluid samples could form a useful supplementary test in the antenatal
      diagnosis of neural tube defects (NTDs). In a 5-year study, 1452 samples of
      middle trimester amniotic fluid were examined blind to the results of other
      antenatal diagnostic tests and to the outcome of pregnancy. Reason of
      amniocentesis included raised serum alpha-fetoprotein (329), previous NTD (73),
      and a family history of NTDs (71). Duplicate cytospin preparations were stained
      with Giemsa and an antibody to glial fibrillary acidic protein (GFAP), and on
      this basis a prediction of fetal NTD status was made which was not communicated
      to clinicians. Subsequent management of pregnancies was influenced only by the
      results of routine antenatal testing for NTDs. Twenty cases of NTDs occurred
      among the 1406 cases in which the outcome was subsequently known. Of these 20
      cases, only five (four anencephalic, one spina bifida) were correctly predicated
      by immunofluorescent identification of GFAP-positive cells in the amniotic fluid.
      The remaining 15 cases (two anencephalic, 13 spina bifida) were not so
      identified. In a further 18 cases, apparently GFAP-positive cells were identified
      in the absence of NTDs. We conclude that GFAP immunofluorescence examination of
      routine amniocentesis samples of amniotic fluid is not a useful predictive test
      for NTDs.

PMID- 7526369
TI  - Monosomy 8q: prenatal diagnosis and autopsy findings.
AB  - The autopsy findings of a fetus with deletion of the long arm of chromosome 8 are
      described. Many of the features are similar to those of the tricho-rhino
      phalangeal syndromes, types I and II, which are associated with deletions on
      chromosome 8q24. Other findings in this case, such as total absence of the corpus
      callosum and intestinal malrotation, have not been described in these syndromes.
      Genes involved in the development of the latter malformations may reside in
      adjacent regions on the long arm of chromosome 8. An elevated serum level of beta
      human chorionic gonadotropin (beta hCG) was found during pregnancy. This
      aberration should be included with other chromosomal disorders which may be
      detected by this test.

PMID- 7526370
TI  - The 48,XXYY syndrome: a case detected by maternal serum alpha-fetoprotein
      screening.
AB  - A 17-year-old woman was referred for amniocentesis due to a low maternal serum
      alpha-fetoprotein (AFP) concentration in a voluntary screening test. The fetal
      karyotype was 48,XXYY, and the pregnancy was terminated. Autopsy of the fetus
      disclosed agenesis of the corpus callosum and unusual facial features.

PMID- 7526371
TI  - [Positive cytokeratin results in malignant melanoma. Pitfall in differential
      immunohistologic diagnosis of occult neoplasms].
AB  - Immunohistology was performed on 84 paraffin-embedded surgical specimens of
      malignant melanomas (MM) from a total of 74 patients. The series consisted of 62
      cutaneous primary tumors and 22 (partly selected) secondary manifestations (9
      cutaneous recurrences and 13 metastases). In 4 patients with lymph node MM
      infiltrates, clinical investigations failed to identify a cutaneous primary
      tumor. In the primary and secondary manifestations respectively, the following
      proportions of immunohistologically positive cases were recorded: vimentin 100%
      each, S100-protein 95% each, NSE 87%/77%, HMB45 97%/64%, NKI/C3 97%/95%,
      cytokeratins (CK) (antibodies KL1, CAM5.2 and 35 beta H11) 0%/23%. Four of the 5
      CK-positive lesions belonged to 3 patients in whom MM had occurred at first or
      exclusively as a lymph node infiltration. These findings confirm the results of
      other authors who report that positive staining results for CK can be expected in
      paraffin sections of secondary manifestations of MM in up to 10% of cases in
      large, nonselected series. This phenomenon appears, however, to be rare in
      primary cutaneous MM.

PMID- 7526372
TI  - [Transmission of hepatitis C by accidental needlestick injuries. Evaluation of
      the risk].
AB  - The risk of transmitting contagious diseases by accidental needle-stick injury
      has raised a considerable amount of concern among hospital staff. Before
      generalized vaccination in the early 80s, there was a high risk of hepatitis B
      transmission. More recently, the development of reliable techniques of detecting
      serum markers has made it possible to precisely evaluate the risk for hepatitis
      C. The risk of contamination by the hepatitis C virus by accidental needle-stick
      injury can be estimated at 0 to 3%, and can only reach a maximum of 10% when the
      patient is positive for hepatitis C RNA. The risk is thus less than for hepatitis
      B virus (7 to 30%). The low rate of transmission probably results from the
      quantity of viral material in blood and secretions. In populations of health
      personnel exposed to a risk of septic needle-stick injury, the prevalence of anti
      hepatitis C virus antibodies has been observed in several studies at rates
      between 0 and 2%. This is similar to non-exposed populations and would be an
      argument suggesting that there is a low risk of hepatitis C virus transmission.
      Nevertheless, because hospital staff is frequently exposed to blood and because a
      significant number of patients are positive for anti-hepatitis C virus
      antibodies, adequate preventive measures must be taken. The Immunization Practice
      Advisory Committee (USA) recommends injection of polyvalent gammaglobulins when
      stick injury occurs with a needle used for a hepatitis C virus antibody positive
      patient, but the effectiveness of this protocol has not been demonstrated.
      Several preliminary studies suggest that treatment of hepatitis C in the acute
      phase could significantly reduce the rate of chronicity. When interferon has been
      authorized for this indication, and if effectiveness is confirmed, treatment
      might be recommended for health personnel with acute needle-stick transmitted HCV
      infection. Infected needle-stick victims might be followed by having their
      transaminases checked 4-12 weeks later. In case of positive results, early
      interferon therapy might be started.

PMID- 7526373
TI  - [Vasoactive peptides of endothelial origin. Therapeutic perspectives].
AB  - The role of the endothelium in vascular tone is well established. New
      physiopathological concepts were brought about by the discovery of endothelium
      derived vasoactive substances such as the vasodilators prostacyclin and
      endothelium-derived relaxing factor (EDRF) or the vasocontrictors endothelin and
      other putative endothelium-derived contracting factors (EDCF). Their discovery
      led to new therapeutic concepts in vascular, respiratory and infectious diseases.
      Prostacyclin is a prostaglandin derived from arachidonic acid which has an
      inhibitor effect on platelet aggregation. It also has a vasodilator effect on
      vascular smooth muscles cells. Prostacyclin analogues are choice vasculoactive
      pharmacological agents for patients with thromboangiitis obliterans or severe
      peripheral vascular disease, whether arteriosclerotic or not. The effect of EDRF
      is vascular dilatation, predominately in the arteries but also in the veins,
      including vessels in grafted tissues. EDRF also inhibits platelet aggregation and
      adhesion. Inversely, the endothelium can also release EDCF which has a
      vasoconstrictor effect. Endothelin, a recently identified 2429 kD EDCF is active
      in both arteries and veins and is implicated in physiologic regulation of
      vasomotricity.

PMID- 7526374
TI  - [Hepatitis C virus and Sjogren's syndrome: is there any link?].

PMID- 7526375
TI  - Hepatitis B surface antigen, hepatitis C virus antibody, body mass index, and
      alcohol drinking among workers with elevated serum alanine aminotransferase.
AB  - METHODS: We conducted a case-control study on liver diseases among Japanese
      workers to examine associations between elevated serum alanine aminotransferase
      (alanine aminotransferase value > or = 50 IU/liter) and selected factors such as
      hepatitis B surface antigen positive, hepatitis C virus antibody positive, body
      mass index, and alcohol drinking. Out of 3,738 workers (1,477 males and 2,261
      females) in a supermarket chain, 91 workers with an elevated serum alanine
      aminotransferase value (> or = 50 IU/liter) were classified as cases and 182
      workers with normal serum alanine aminotransferase value and without an episode
      of blood transfusion were randomly selected as controls. RESULTS: Prevalence
      rates of hepatitis B surface antigen positive and hepatitis C virus antibody
      positive were 4.4 and 23.1% among the overall cases, 2.9 and 11.8% among the
      cases with 100 > alanine aminotransferase value > or = 50, and 8.7 and 56.5%
      among the cases with alanine aminotransferase value > or = 100. A logistic
      regression analysis was conducted. Odds ratios were 4.94 for hepatitis B surface
      antigen positive (P < 0.05) and 77.19 for hepatitis C virus antibody positive (P
      < 0.001). Odds ratios for body mass index increased with increasing body mass
      index values; 3.32 for 26 > body mass index > or = 24 (P < 0.01) and 5.03 for
      body mass index > or = 26 (P < 0.001). No increased risk was observed among
      regular drinkers of less than 27 g/day of ethanol (odds ratio is 0.23) or of 27
      53 g/day of ethanol (odds ratio is 0.47). A slightly increased odds ratio of 1.35
      was observed among regular drinkers of 54-81 g/day of ethanol, but this was not
      statistically significant. CONCLUSIONS: Our results suggest that hepatitis C
      virus and high body mass index are predominant factors in elevated serum alanine
      aminotransferase levels among Japanese workers, while alcohol drinking is a minor
      factor.

PMID- 7526376
TI  - [Mobility and the environment].

PMID- 7526377
TI  - Heterogeneity in the plasma levels of two acute-phase proteins in mice from
      inbred strains infected with Trypanosoma cruzi.
AB  - We analyzed the variations observed in the plasma levels of both alpha
      macroglobulins (AM) and serum amyloid P (SAP) in mice from three different inbred
      strains (C3H, Balb/C and C57black/6) acutely infected with Trypanosoma cruzi. SAP
      levels increased in C57black/6 and Balb/C mice but not C3H mice. AM levels
      increased in all C3H mice but not in C57black/6 mice and rose slightly in only
      43% of the Balb/C mice. AM and SAP levels are differently modulated in patterns
      that may be strain-determined.

PMID- 7526378
TI  - Engineering of protein epitopes: a single deletion in a snake toxin generates
      full binding capacity to a previously unrecognized antibody.
AB  - Structural features associated with the ability of a monoclonal antibody (mAb) to
      discriminate between protein variants are identified and engineered. The variants
      are the curaremimetic toxin alpha from Naja nigricollis and erabutoxin a or b
      from Laticauda semifasciata, which differ from each other by 16 substitutions and
      one insertion. The neutralizing mAb M alpha 1 recognizes with high affinity a
      topographical epitope on the surface of toxin alpha, but fails to recognize the
      erabutoxins although they possess most of the residues forming the presumed
      epitope. Examinations of the toxin alpha and erabutoxin 3-D structures and
      molecular dynamics simulations reveal several differences between the variants.
      In particular, the region involving the beta-turn 17-24 is organized differently.
      Analysis of the differences found in this region suggest that the insertion (or
      deletion) at position 18 of the variant amino acid sequences is particularly
      important in determining the differential cross-reactivity. To test this
      proposal, residue 18 was deleted in one erabutoxin using site-directed
      mutagenesis, and the biological properties of the resulting mutant were examined.
      We found that full antigenicity was restored in the previously unrecognized
      variant. The implications of this finding are discussed.

PMID- 7526379
TI  - Cholera toxin B subunit: an efficient transmucosal carrier-delivery system for
      induction of peripheral immunological tolerance.
AB  - Oral administration of antigens, including allergens and autoantigens, may be an
      efficient way to prevent diseases associated with untoward immune responses to
      self- and non-self-antigens. However, this approach has met with limitations
      because it usually requires repeated administrations of large doses of antigen
      and is less efficient in an already immune host, and the effect is of short
      duration. We report that a single oral administration of minute amounts of
      particulate or soluble antigen coupled to the B subunit of cholera toxin (CTB)
      can markedly suppress systemic immune responses in naive and in systemically
      immune animals. Both early (2-4 hr) and late (24-48 hr) delayed type
      hypersensitivity reactivities were strongly suppressed after feeding a single
      dose of CTB-conjugated antigen. Serum antibody responses were also decreased,
      although moderately, after oral administration of CTB-conjugated antigen. This
      strategy of tolerance induction, based on oral administration of small amounts of
      antigens conjugated to a mucosa-binding molecule, may find broad applications for
      preventing or abrogating untoward immune responses.

PMID- 7526381
TI  - Purification and characterization of a kinase specific for the serine- and
      arginine-rich pre-mRNA splicing factors.
AB  - Members of the SR family of pre-mRNA splicing factors are phosphoproteins that
      share a phosphoepitope specifically recognized by monoclonal antibody (mAb) 104.
      Recent studies have indicated that phosphorylation may regulate the activity and
      the intracellular localization of these splicing factors. Here, we report the
      purification and kinetic properties of SR protein kinase 1 (SRPK1), a kinase
      specific for SR family members. We demonstrate that the kinase specifically
      recognizes the SR domain, which contains serine/arginine repeats. Previous
      studies have shown that dephosphorylated SR proteins did not react with mAb 104
      and migrated faster in SDS gels than SR proteins from mammalian cells. We show
      that SRPK1 restores both mobility and mAB 104 reactivity to a SR protein SF2/ASF
      (splicing factor 2/alternative splicing factor) produced in bacteria, suggesting
      that SRPK1 is responsible for the generation of the mAb 104-specific
      phosphoepitope in vivo. Finally, we have correlated the effects of mutagenesis in
      the SR domain of SF2/ASF on splicing with those on phosphorylation of the protein
      by SRPK1, suggesting that phosphorylation of SR proteins is required for
      splicing.

PMID- 7526380
TI  - Multiple ligands for cytoadherence can be present simultaneously on the surface
      of Plasmodium falciparum-infected erythrocytes.
AB  - A major virulence factor of Plasmodium falciparum is the adherence of parasitized
      erythrocytes to the wall of postcapillary venules via a specific interaction
      between parasite-derived erythrocyte surface ligands and receptors on endothelial
      cells. To study this phenomenon in vitro, we selected a parasite population that
      expressed at least two different ligands and demonstrated that parasitized cells
      may coexpress ligands with specificity for multiple receptors. This selected
      parasite line had several antigenic and cytoadherence characteristics that were
      different from those of the parent line. Single parasitized erythrocytes were
      able to adhere to three distinct receptors via at least two separate ligands; a
      trypsin-sensitive molecule mediated cytoadherence to CD36 and intercellular
      adhesion molecule 1 and a trypsin-insensitive molecule(s) was responsible for
      adherence to a third receptor on the surface of melanoma cells. We present
      evidence that this newly discovered receptor for cytoadherence is an N-linked
      glycosaminoglycan, as treatment of melanoma cells with endoglycosidase H
      abolished cytoadherence. These observations emphasize the adaptability of P.
      falciparum and the complexity of the cytoadherence phenomenon.

PMID- 7526383
TI  - Autoreactive CD8+ T-cell responses to human myelin protein-derived peptides.
AB  - Identification of the targets of autoreactive T cells is important for
      understanding the pathogenesis of many autoimmune diseases. In multiple
      sclerosis, myelin proteins are thought to be the targets of autoreactive T-cell
      responses. To date only major histocompatibility complex class II-restricted CD4+
      T-cell responses to myelin proteins have been investigated. In the present study,
      the ability of self peptides derived from human myelin proteins to induce
      autoreactive CD8+ T-cell responses has been assessed. Peptide sequences from
      human myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated
      glycoprotein (MAG), and myelin oligodendrocyte glycoprotein have been identified
      that bind to and form stable complexes with HLA-A2. MBP 110-118, PLP 80-88, MAG
      287-295, MAG 509-517, and MAG 556-564 were all able to induce peptide-specific
      HLA-A2-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses in vitro in HLA-A2+
      individuals. CTLs specific for MBP 110-118 and MAG 556-564 could recognize
      endogenously processed antigens presented by HLA-A2. CTL clones reactive to MBP
      110-118 and MAG 556-564 produced tumor necrosis factor alpha and a subset of
      these clones also produced interferon gamma. These results demonstrate that (i)
      self peptides derived from human myelin proteins can induce autoreactive CD8+
      CTLs and (ii) these CD8+ T cells produce cytokines thought to be important in
      mediating demyelinating disease. These studies provide an experimental approach
      for the assessment of CD8+ T-cell responses in such autoimmune diseases.

PMID- 7526382
TI  - Immune function in mice lacking the perforin gene.
AB  - Mice lacking the perforin gene were generated by using targeted gene disruption
      in embryonal stem cells. When infected with lymphocytic choriomeningitis virus
      (LCMV), perforin-less (-/-) mice showed clear signs of having mounted an immune
      response based on activation of CD8 T cells but were unable to clear the LCMV
      infection. This failure to eliminate virus was accompanied by a failure to
      generate spleen cells capable of lysing LCMV-infected fibroblasts in vitro.
      Spleen cells from LCMV-infected -/- mice were able to lyse hematopoietic target
      cells after exposure to phorbol 12-myristate 13-acetate and ionomycin, provided
      the target cells expressed the Fas antigen. Spleen cells from -/- mice also
      responded to alloantigen in mixed leukocyte culture by blastogenesis and
      proliferation. The resulting cells were able to lyse hematopoietic target cells,
      although not as well as spleen cells from +/+ littermates sensitized in the same
      manner. However, lysis by -/- cells was again seen only if the target cells
      expressed Fas antigen. We conclude that perforin-less -/- mice retain and express
      the Fas lytic pathway as expressed in vitro but that this pathway is insufficient
      to clear an LCMV infection in vivo.

PMID- 7526384
TI  - Protein-tyrosine phosphorylation regulates apoptosis in human eosinophils and
      neutrophils.
AB  - Early signaling events that control the process of programmed cell death are
      largely unknown. Tyrosine phosphorylation plays a major role in transmembrane
      signal transduction through most cell surface receptors. Granulocyte/macrophage
      colony-stimulating factor (GM-CSF), a cytokine released by activated T cells, has
      been shown to increase tyrosine phosphorylation in several cells and to inhibit
      granulocyte cell death in vitro. In this study, we demonstrate that the effect of
      GM-CSF on granulocyte cell death can be blocked by the tyrosine kinase inhibitor
      genistein, suggesting that increases in tyrosine phosphorylation are essential to
      inhibit cell death. To analyze the role of tyrosine phosphorylation for the
      regulation of granulocyte cell death more precisely, we increased levels of
      tyrosine phosphorylation using the protein-tyrosine phosphatase inhibitor
      phenylarsine oxide (PAO). Similar to GM-CSF, treatment of the cells with PAO was
      followed by high increases in tyrosine phosphorylation and inhibition of
      programmed cell death in human eosinophils and neutrophils. Strikingly, at low
      concentrations of the inhibitor and low induction of tyrosine phosphorylation,
      acceleration of apoptosis was observed. Genistein and herbimycin A reversed the
      effects of PAO on tyrosine phosphorylation and granulocyte apoptosis. These
      results suggest that programmed eosinophil and neutrophil death is regulated by
      early events of signal transduction pathways such as tyrosine phosphorylation.

PMID- 7526385
TI  - Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine
      phosphorylated CD3 zeta chain.
AB  - The CD45 transmembrane protein-tyrosine phosphatase (PTPase, EC 3.1.3.48) plays
      an essential role in T-cell activation by activating the Lck and/or Fyn protein
      tyrosine kinases. However, numerous experiments have indicated that CD45 may have
      both stimulatory and inhibitory roles in T-cell activation. Thus, it is unlikely
      that the two kinases are the sole substrates of the CD45 PTPase. Furthermore, the
      complex regulation of the alternative splicing of the extracellular domain in
      various leukocyte lineages also suggests additional roles for the CD45 PTPase. To
      identify such functions, it is necessary to identify physiologically relevant
      substrates of the CD45 PTPase other than the two protein-tyrosine kinases. To
      this end, we searched for high-affinity substrates of the CD45 PTPase among the
      tyrosine-phosphorylated T-cell proteins by using purified glutathione S
      transferase-CD45 fusion molecules. The enzymatically inactive CD45 C828S mutant
      protein, in which the cysteine residue at the catalytic center was changed to a
      serine residue, bound tightly to the phosphorylated CD3 zeta chain. This binding
      was specific to CD45 PTPase, as neither the leukocyte common antigen-related
      molecule (LAR) PTPase nor the CD45-LAR hybrid PTPases bound the phosphorylated
      CD3 zeta chain. Furthermore, phosphorylated CD3 zeta chain was preferentially
      dephosphorylated by the wild-type CD45 PTPase under conditions that did not
      significantly dephosphorylate other cellular proteins. Thus, the phosphorylated
      CD3 zeta chain is a specific and high-affinity substrate of the CD45 PTPase.
      These results suggest that CD45 is involved in the termination of the T-cell
      response via dephosphorylation of CD3 zeta chain.

PMID- 7526386
TI  - Modulatory effect of the transmembrane domain of the protein-tyrosine kinase
      encoded by oncogene ros: biological function and substrate interaction.
AB  - There is a 3-aa insertion in the transmembrane (TM) domain of the p68gag-ros
      protein-tyrosine kinase encoded by avian sarcoma virus UR2 v-ros as compared with
      that of the protooncogene c-ros. The effect of this insertion on biological
      function and biochemical properties of v-Ros protein was investigated by deleting
      these 3 aa to generate the mutant TM1. This mutant has greatly reduced
      transforming, mitogenic, and tumorigenic activities despite the fact that the
      protein-tyrosine kinase activity and cell-surface localization of TM1 protein are
      unaffected. However, unlike UR2 protein, mutant TM1 protein becomes glycosylated,
      is differentially phosphorylated, and fails to induce tyrosine phosphorylation of
      a 88-kDa protein and a major substrate of insulin receptor, insulin receptor
      substrate 1. The TM1 protein is unable to associate with phosphatidylinositol 3
      kinase and fails to promote association of insulin receptor substrate 1 with
      phosphatidylinositol 3-kinase. By contrast, tyrosine phosphorylation of Shc
      protein and phospholipase C gamma as well as interaction of Grb2 protein with Shc
      and SOS protein signaling components are unaltered in the TM1 infected cells. Our
      results show that the TM-domain sequence of p68gag-ros profoundly affects its
      function and substrate interaction. The mutant defines a signaling pathway
      including phosphatidylinositol 3-kinase, insulin receptor substrate 1, and
      possibly an 88-kDa protein that does not overlap the Ras pathway and is important
      for full transforming and mitogenic potency of v-ros protein-tyrosine kinase.

PMID- 7526387
TI  - Formation of free nitric oxide from l-arginine by nitric oxide synthase: direct
      enhancement of generation by superoxide dismutase.
AB  - Although nitric oxide (NO) appears to be one of the oxidation products of L
      arginine catalyzed by NO synthase (NOS; EC 1.14.13.39), past studies on the
      measurement of NO in cell-free enzymatic assays have not been based on the direct
      detection of the free NO molecule. Instead, assays have relied on indirect
      measurements of the stable NO oxidation products nitrite and nitrate and on
      indirect actions of NO such as guanylate cyclase activation and oxyhemoglobin
      oxidation. Utilizing a specific chemiluminescence assay, we report here that the
      gaseous product of L-arginine oxidation, catalyzed by both inducible macrophage
      and constitutive neuronal NOS, is indistinguishable from authentic NO on the
      basis of their physicochemical properties. NO gas formation by NOS was dependent
      on L-arginine, NADPH, and oxygen and inhibited by NG-methyl-L-arginine and
      cyanide anion. Superoxide dismutase (SOD) caused a marked, concentration
      dependent increase in the production of free NO by mechanisms that were unrelated
      to the dismutation of superoxide anion or activation of NOS. These observations
      indicate that free NO is formed as a result of NOS-catalyzed L-arginine oxidation
      and that SOD enhances the generation of NO without directly affecting NO itself.
      SOD appears to elicit a novel biological action, perhaps accelerating the
      conversion of an intermediate in the L-arginine-NO pathway such as nitroxyl (HNO)
      to NO.

PMID- 7526388
TI  - Cloning and expression of AQP3, a water channel from the medullary collecting
      duct of rat kidney.
AB  - The terminal part of the inner medullary collecting duct exhibits a high degree
      of water permeability that is independent of increased intracellular cAMP and not
      accounted for by the activity of the known renal epithelial water channels CHIP28
      (28-kDa channel-forming integral protein) and WCH-CD (collecting duct water
      channel protein). Starting with rat kidney papilla mRNA, reverse transcription
      PCR was performed with degenerate primers assuming that the putative channel
      would be a member of the major intrinsic protein (MIP) family of proteins. A cDNA
      fragment was identified and used to screen a rat kidney cDNA library. A 1.9-kb
      cDNA clone was isolated. The open reading frame of 876 bp coded for a protein of
      292 amino acids (M(r), 31,431). Aquaporin 3 (AQP3; 31.4-kDa water channel
      protein) is a newly discovered member of the MIP family. Northern blot analysis
      showed a single transcript for AQP3 of approximately 1.9 kb present in the renal
      medulla, predominantly in the inner medulla. With in situ hybridization, abundant
      message was found in the cells of the medullary collecting ducts. Injection of
      the complementary RNA of AQP3 into Xenopus oocytes markedly increased the osmotic
      water permeability. This permeability had an energy of activation of 3.0 kcal/mol
      (1 cal = 4.184 J), it was fully blocked by 1 mM p-chloromercuriphenylsulfonate,
      and this inhibition was reversed by 5 mM dithiothreitol. cAMP did not increase
      this water permeability. AQP3 did not permit passage of monovalent ions (Na, K,
      Cl); however, it is slightly permeable to urea. The present study demonstrates
      the existence of an additional water channel, AQP3, in epithelial cells of the
      medullary collecting duct.

PMID- 7526389
TI  - A Drosophila gene promoter is subject to glucose repression in yeast cells.
AB  - Previous work has shown that the alpha-amylase gene of Drosophila melanogaster is
      subject to repression by dietary glucose. Moreover, glucose repression of this
      gene is mediated by promoter elements that lie upstream of the transcriptional
      start site. In this study, we examined the activity of the glucose-repressible
      Drosophila promoter in transformed yeast cells. We show that the amylase promoter
      region can mediate glucose repression of a heterologous reporter gene in yeast.
      The implication of this result is that the yeast regulatory machinery can
      recognize the Drosophila promoter signals. This, in turn, implies an unexpectedly
      high degree of evolutionary conservation in the mechanism of glucose repression
      among eukaryotes. It also shows that genes that have acquired complex patterns of
      developmental regulation-e.g., the Drosophila amylase gene, can still retain,
      intact, more primitive forms of regulation, such as glucose repression.

PMID- 7526390
TI  - Pseudoknot in the central domain of small subunit ribosomal RNA is essential for
      translation.
AB  - Phylogenetic comparison of rRNA sequences has suggested that a pseudoknot
      structure exists in the central domain of small-subunit rRNA. In Escherichia coli
      16S rRNA, this pseudoknot would form when positions 570 and 571 pair with
      positions 865 and 866. Mutations were introduced into this pseudoknot at the
      phylogenetically invariant nucleotides U571 and A865. Single mutations of U to A
      at 571 or A to U at 865 dramatically altered the structural stability of the 30S
      subunit and also impaired the function of the subunit in translation. When the
      mutations were combined to create a compensatory pairing, the normal structure of
      the 30S subunit was restored, and the function of the mutant subunit in
      translation returned to wild-type levels. These results demonstrate the existence
      of a higher order structure in rRNA that directly affects the folding of the 30S
      subunit. Given the position of this structure in the three-dimensional model of
      the small subunit and the additional interactions that are likely to form in the
      same rRNA region, the central domain pseudoknot appears to contribute to a
      complex structure of rRNA that controls the conformational state of the ribosome.

PMID- 7526391
TI  - Expression of a functional human complement inhibitor in a transgenic pig as a
      model for the prevention of xenogeneic hyperacute organ rejection.
AB  - The serious shortage of human organs available for transplantation has engendered
      a heightened interest in the use of animal organs (xenografts) for
      transplantation. However, the major barrier to successful discordant xenogeneic
      organ transplantation is the phenomenon of hyperacute rejection. Hyperacute
      rejection results from the deposition of high-titer preformed antibodies that
      activate serum complement on the luminal surface of the vascular endothelium,
      leading to vessel occlusion and graft failure within minutes to hours. Although
      endogenous membrane-associated complement inhibitors normally protect endothelial
      cells from autologous complement, they are species restricted and thus confer
      limited resistance to activated xenogeneic complement. To address the
      pathogenesis of hyperacute rejection in xenotransplantation, transgenic mice and
      a transgenic pig were engineered to express the human terminal complement
      inhibitor hCD59. High-level cell surface expression of hCD59 was achieved in a
      variety of murine and porcine cell types, most importantly on both large vessel
      and capillary endothelium. hCD59-expressing porcine cells were significantly
      resistant to challenge with high-titer anti-porcine antibody and human
      complement. These experiments demonstrate a strategy for developing a pig-to
      primate xenogeneic transplantation model to test whether the expression of a
      human complement inhibitor in transgenic pigs could render xenogeneic organs
      resistant to hyperacute rejection.

PMID- 7526392
TI  - The ability of the immunophilin FKBP59-HBI to interact with the 90-kDa heat shock
      protein is encoded by its tetratricopeptide repeat domain.
AB  - A protein of apparent molecular mass of approximately 59 kDa of the FK506-binding
      protein class (FKBP59) has been found associated with the heat shock protein
      hsp90 included in nontransformed steroid receptor complexes and termed FKBP59-HBI
      (HBI for Heat shock protein 90 Binding Immunophilin). Further data analysis has
      revealed that this immunophilin also belongs to the tetratricopeptide repeat
      family of proteins. In this work, we describe the hsp90-binding domain of FKBP59
      HBI. Density gradient centrifugation, gel filtration, and immunoadsorption
      analyses failed to demonstrate a stable association between FKBP59-HBI and hsp90
      in the rabbit reticulocyte lysate. Using a gel-retardation assay, we provide
      evidence for a specific ATP-independent interaction between highly purified wild
      type rabbit FKBP59-HBI and human hsp90 beta. This interaction was not affected by
      the immunosuppressants FK506 and rapamycin. Examination of the behavior of
      several mutants led us to conclude that the tetratricopeptide motifs localized in
      the C-terminal part of FKBP59-HBI are necessary for hsp90 binding.

PMID- 7526393
TI  - Transphosphorylation as the mechanism by which the high-affinity receptor for IgE
      is phosphorylated upon aggregation.
AB  - When aggregated, the high-affinity receptors for IgE on mast cells (Fc epsilon
      RI) launch a series of phosphorylations, particularly of protein tyrosines. We
      have analyzed how aggregation initiates this cascade. We examined Fc epsilon RI
      from unstimulated cells and from cells exposed to a polyvalent hapten conjugate
      that aggregates the Fc epsilon RI via the receptor-bound anti-hapten IgE. We also
      examined the latter receptors after they had been disaggregated in vitro with
      monovalent hapten. By an in vitro kinase assay: (i) Unaggregated and
      disaggregated receptors are associated with a kinase that phosphorylates an
      exogenous (peptide) substrate but minimally, or not at all, the subunits of Fc
      epsilon RI or associated proteins (endogenous substrates). After aggregation,
      phosphorylation of the exogenous substrate is linear with time, but the
      modification of the endogenous substrates reaches a plateau, presumably because
      only those endogenous substrates that are adjacent to the kinase are
      phosphorylated. (ii) Aggregated receptors and disaggregated receptors have
      enhanced kinase activity toward exogenous substrate. The state of phosphorylation
      of the receptor correlates strongly with the yield of enhanced kinase activity.
      We propose that upon aggregation of Fc epsilon RI, a constitutively associated
      kinase phosphorylates endogenous substrates by transphosphorylation. As a result,
      additional kinase activity becomes manifest and this promotes further
      transphosphorylation. In view of the homology between Fc epsilon RI and other
      receptors central to the immune response, the latter receptors likely utilize a
      similar transphosphorylation mechanism.

PMID- 7526394
TI  - Aggregation of the high-affinity IgE receptor and enhanced activity of p53/56lyn
      protein-tyrosine kinase.
AB  - Aggregation of the receptor with high affinity for IgE (Fc epsilon RI) on the
      surface of mast cells and basophils stimulates phosphorylation of protein
      tyrosines, a process in which p53/56lyn kinase has been implicated. We measured
      the association between Fc epsilon RI and the kinase, using chemical crosslinking
      to stabilize their interaction. In the rat basophilic leukemia mast cell line, 3
      4%, and at most 20%, of Fc epsilon RI appear to be associated with the kinase
      prior to aggregation, even though there is an excess of total cell lyn kinase.
      Aggregating the Fc epsilon RI causes three to four times more of the kinase to
      associate with receptors, a process requiring a prior phosphorylation step. In an
      in vitro assay, the lyn associated with the aggregated receptors becomes
      disproportionately more phosphorylated than would be predicted from the amount of
      lyn associated with the receptors. These and other data are consistent with a
      model in which aggregation of the receptor leads to its transphosphorylation by
      constitutively associated lyn kinase. We propose that additional molecules of
      this kinase are thereby recruited and that this markedly enhances
      transphosphorylation of tyrosine on the receptor and associated proteins, thereby
      initiating a cascade of further biochemical changes. This model is also
      consistent with data on receptors such as the clonotypic receptors on B and T
      lymphocytes, which share structural and functional features with Fc epsilon RI.

PMID- 7526395
TI  - Activity-dependent current distributions in model neurons.
AB  - The electrical activity of a neuron can affect its intrinsic physiological
      characteristics through a wide range of processes. We study a computer-simulated
      multicompartment model neuron in which channel density depends on local Ca2+
      concentrations. This has three interesting consequences for the spatial
      distribution of conductances and the physiological behavior of the neuron: (i)
      the model neuron spontaneously develops a realistic, nonuniform distribution of
      conductances that is linked both to the morphology of the neuron and to the
      pattern of synaptic input that it receives, (ii) the response to synaptic input
      reveals a form of intrinsic localized plasticity that balances the synaptic
      contribution from dendritic regions receiving unequal stimulation, and (iii)
      intrinsic plasticity establishes a biophysical gain control that restores the
      neuron to its optimal firing range after synapses are strengthened by "Hebbian"
      long-term potentiation.

PMID- 7526396
TI  - Domains of Escherichia coli primase: functional activity of a 47-kDa N-terminal
      proteolytic fragment.
AB  - Endoproteinase Asp-N cleaves the 581-amino acid Escherichia coli primase (65,564
      Da) into several major fragments. One of these, a 47-kDa fragment containing the
      complete N terminus and the first 422 amino acids of primase, is capable of
      primer RNA (pRNA) synthesis in the G4oric/single-stranded DNA binding
      protein/primase pRNA synthesis system. A cloned 398-amino acid N-terminal
      fragment of primase can also synthesize pRNA. The sizes of the pRNA synthesized
      by these N-terminal fragments, however, are smaller than those synthesized by
      intact primase, suggesting that the C-terminal region of primase plays a role in
      processivity or regulation of pRNA synthesis. Primase mutants with the last 10
      and 40 C-terminal amino acids deleted synthesize pRNA as wild-type primase,
      indicating that any regulatory sequences must be internal to the C terminus of
      primase.

PMID- 7526397
TI  - A low-affinity estrogen-binding site in pregnant rat uteri: analysis and partial
      purification.
AB  - We have identified a low-affinity (type II) estrogen-binding site (EBS) that is
      expressed at high levels during pregnancy in rat uteri. Although this activity
      was detectable in nonpregnant rat uteri, it was present in amounts (0.094 pmol/g
      of uteri) that were severalfold lower than the high-affinity type I estrogen
      receptor (0.57 pmol/g of uteri). During pregnancy, at 19-20 days of gestation,
      the low-affinity type II EBS became the major (> or = 88%) estrogen-binding site
      in rat uteri. The increase in the level of low-affinity EBS (7.9 pmol/g) in uteri
      was approximately 85-fold with an approximately 20-fold increase in the specific
      activity (0.39 pmol/mg) of this form, whereas the high-affinity form remained
      relatively unchanged. We report here a method of purification of type II EBS from
      pregnant rat uteri and present an analysis of its DNA and steroid-binding
      properties. Estradiol-binding studies and Scatchard analysis showed that the type
      II EBS had an apparent estradiol-binding affinity of > or = 24 nM. Gel filtration
      and SDS/PAGE analysis indicated that the type II EBS was a monomeric 73-kDa
      protein. The estradiol binding remained apparently uninhibited in the presence of
      a large excess of tamoxifen, nafoxidine, or dihydrotestosterone. Estradiol,
      diethylstilbestrol, and quercitin (a type II EBS-specific inhibitor) competed
      efficiently. The purified low-affinity EBS did not have sequence-specific DNA
      binding activity with the estrogen-responsive element, which indicated that it
      differs in function from the type I estrogen receptor.

PMID- 7526398
TI  - Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B
      signal transduction pathway.
AB  - Studies presented here show that overall NF-kappa B signal transduction begins
      with a parallel series of stimuli-specific pathways through which cytokines
      (tumor necrosis factor alpha), oxidants (hydrogen peroxide and mitomycin C), and
      phorbol ester (phorbol 12-myristate 13-acetate) individually initiate signaling.
      These initial pathways culminate in a common pathway through which all of the
      stimulating agents ultimately signal NF-kappa B activation. We distinguish the
      stimuli-specific pathways by showing that the oxidative stimuli trigger NF-kappa
      B activation in only one of two human T-cell lines (Wurzburg but not Jurkat),
      whereas tumor necrosis factor alpha and phorbol 12-myristate 13-acetate readily
      stimulate in both lines. We propose the common pathway as the simplest way of
      accounting for the common requirements and properties of the signaling pathway.
      We include a redox-regulatory mechanism(s) in this common pathway to account for
      the previously demonstrated redox regulation of NF-kappa B activation in Jurkat
      cells (in which oxidants don't activate NF-kappa B); we put tyrosine
      phosphorylation in the common pathway by showing that kinase activity
      (inhibitable by herbimycin A and tyrphostin 47) is required for NF-kappa B
      activation by all stimuli tested in both cell lines. Since internal sites of
      oxidant production have been shown to play a key role in the cytokine-stimulated
      activation of NF-kappa B, and since tyrosine kinase and phosphatase activities
      are known to be altered by oxidants, these findings suggest that intracellular
      redox status controls NF-kappa B activation by regulating tyrosine
      phosphorylation event(s) within the common step of the NF-kappa B signal
      transduction pathway.

PMID- 7526399
TI  - A role for the acetylcholine receptor-inducing protein ARIA in oligodendrocyte
      development.
AB  - ARIA acetylcholine receptor-inducing activity protein, is a member of a family of
      ligands that includes the Neu differentiation factor, heregulin, and glial growth
      factor. These ligands all act through one or more receptor tyrosine kinases of
      approximately 185 kDa. In some conditions these ligands promote proliferation,
      whereas in others they induce differentiation. ARIA was originally isolated from
      chick brain on the basis of its ability to induce synthesis of nicotinic
      acetylcholine receptors in skeletal muscle. In this paper we show that ARIA is
      expressed in the subventricular zone of the rat brain and that it enhances the
      development of oligodendrocytes from bipotential (O2A) glial progenitor cells. We
      have also found that ARIA induces tyrosine phosphorylation of a 185-kDa protein
      in O2A progenitor cells. ARIA does not increase bromodeoxyuridine incorporation
      by oligodendrocytes but is mitogenic when added to Schwann cells in vitro. Thus,
      ARIA accelerates the formation of oligodendrocytes in vitro and is expressed
      where it could exercise the same influence in vivo.

PMID- 7526400
TI  - Molecular dynamics simulation of the gramicidin channel in a phospholipid
      bilayer.
AB  - A molecular dynamics simulation of the gramicidin A channel in an explicit
      dimyristoyl phosphatidylcholine bilayer was generated to study the details of
      lipid-protein interactions at the microscopic level. Solid-state NMR properties
      of the channel averaged over the 500-psec trajectory are in excellent agreement
      with available experimental data. In contrast with the assumptions of macroscopic
      models, the membrane/solution interface region is found to be at least 12 A
      thick. The tryptophan side chains, located within the interface, are found to
      form hydrogen bonds with the ester carbonyl groups of the lipids and with water,
      suggesting their important contribution to the stability of membrane proteins.
      Individual lipid-protein interactions are seen to vary from near 0 to -50
      kcal/mol. The most strongly interacting conformations are short-lived and have a
      nearly equal contribution from both van der Waals and electrostatic energies.
      This approach for performing molecular dynamics simulations of membrane proteins
      in explicit phospholipid bilayers should help in studying the structure,
      dynamics, and energetics of lipid-protein interactions.

PMID- 7526401
TI  - Kinking of DNA and RNA helices by bulged nucleotides observed by fluorescence
      resonance energy transfer.
AB  - Fluorescence resonance energy transfer (FRET) has been used to demonstrate the
      bending of DNA and RNA helices for three series of double-stranded molecules
      containing bulge loops of unopposed adenosine nucleotides (An, n = 0-9).
      Fluorescein and rhodamine were covalently attached to the 5' termini of the two
      component strands. Three different methods were applied to measure the FRET
      efficiencies. The extent of energy transfer within each series increases as the
      number of bulged nucleotides varies from 1 to 7, indicating a shortening of the
      end-to-end distance. This is consistent with a bending of DNA and RNA helices
      that is greater for larger bulges. The FRET efficiency for DNA molecules with A9
      bulges is lower than the efficiency for the corresponding A7 bulged molecules,
      although the A9 molecules exhibit increased electrophoretic retardation. Ranges
      of bending angles can be estimated from the FRET results.

PMID- 7526402
TI  - Disruption of the compacted myelin sheath of axons of the central nervous system
      in proteolipid protein-deficient mice.
AB  - The isoproteins proteolipid protein (PLP) and DM20, the two major integral
      membrane proteins of central nervous system (CNS) myelin, are encoded by a single
      gene on the X chromosome and show a different developmental expression pattern.
      To investigate their functions in myelin structure and myelination, we produced
      transgenic mice carrying a targeted alteration of the X chromosome-linked Plp
      gene containing a deletion within exon III, mimicking DM20, and a neo cassette in
      reverse orientation within intron III. Here we show that the antisense
      integration of the neo cassette disrupts the expression of the Plp gene. The
      ultrastructure of the multilayer myelin sheath of all axons in the CNS of
      hemizygous male or homozygous female PLP/DM20-deficient mice is highly
      disordered. The apposition of the extracytoplasmic surfaces and thereby the
      intraperiod dense line is lacking. The disrupted assembly of the myelin sheath
      leads to a profound reduction of conductance velocities of CNS axons, impairments
      in neuromotor coordination, and behavioral changes.

PMID- 7526403
TI  - Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of
      the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation.
AB  - The cGMP-gated cation channel mediating visual transduction in retinal rods was
      recently found to comprise at least two subunits, 1 and 2 (or alpha and beta).
      SDS gels of the purified channel show, in addition to a 63-kDa protein band
      (subunit 1), a 240-kDa protein band that binds Ca(2+)-calmodulin, a modulator of
      the channel. To examine any connection between subunit 2 and the 240-kDa protein,
      cGMP-gated channels formed from the expressed cloned subunits in human embryonic
      kidney (HEK) 293 cells were tested for Ca(2+)-calmodulin effect. Homooligomeric
      channels formed by subunit 1 alone showed no sensitivity to Ca(2+)-calmodulin,
      and neither did heterooligomeric channels formed by subunit 1 and the short
      alternatively spliced form of subunit 2 (2a). By contrast, the cGMP half
      activation constant (K1/2) for heterooligomeric channels formed from subunit 1
      and the long form of subunit 2 (2b) was increased 1.5- to 2-fold by Ca(2+)
      calmodulin, similar to the increase observed for the native channel. In Western
      blots of rod outer segment membranes, a subunit 2-specific antibody also
      recognized the 240-kDa protein. Finally, amino acid sequences derived from
      peptide fragments of the bovine 240-kDa protein showed approximately 80% identity
      to regions of subunit 2b of the human channel. These results together suggest
      that subunit 2b of the rod channel is a component of the 240-kDa protein and that
      it mediates the Ca(2+)-calmodulin modulation of the channel.

PMID- 7526404
TI  - A deficit in care. The educational needs of thoracic patients.
AB  - 1. There is a need for increased educational input for thoracic surgical
      patients. 2. Information and health education are important aspects of holistic
      care. 3. Care plans should aim to help the patient regain and maintain a level of
      independence. 4. Discharge planning should ideally begin prior to admission for
      surgery.

PMID- 7526405
TI  - Mechanisms of chemical injury of thyroid gland.
AB  - Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in
      rodents exert a direct effect on the thyroid gland to disrupt one of several
      steps in the biosynthesis and secretion of thyroid hormones. This includes 1)
      inhibition of the iodine-trapping mechanism (thiocyanate or perchlorate), 2)
      blockage of organic binding of iodine and coupling of iodothyronines to form
      thyroxine (T4) and triiodothyronine (T3) (e.g., sulfonamides, thiourea,
      methimazole, and aminotriazole, among others), and 3) inhibition of thyroid
      hormone secretion by an effect on proteolysis of active hormone from the colloid
      (lithium or an excess of iodide). Another large group of goitrogenic chemicals
      disrupts thyroid hormone economy by increasing the peripheral metabolism of
      thyroid hormones through an induction of hepatic microsomal enzymes. This group
      includes CNS-acting drugs (phenobarbital, benzodiazepines), calcium channel
      blockers (nicardipine, nifedipine), steroids (spironolactone), retinoids,
      chlorinated hydrocarbons (chlordane, DDT, TCDD), polyhalogenated biphenyls (PCB,
      PBB), and enzyme inducers. Thyroid hormone economy also can be disrupted by
      xenobiotics that inhibit the 5'monodeiodinase, which converts T4 in peripheral
      sites (e.g., liver and kidney) to biologically active T3. Inhibition of this
      enzyme by FD&C Red No. 3, amiodarone, and iopanoic acid lowers circulating T3
      levels, which results in a compensatory increased secretion of thyroid
      stimulating hormone (TSH), follicular cell hypertrophy and hyperplasia, and an
      increased incidence of follicular cell tumors in 2-year or lifetime studies in
      rats. Physiologic perturbations alone such as the feeding of an iodine-deficient
      diet, partial thyroidectomy, natural goitrogens in certain foods, and
      transplantation of TSH-secreting pituitary tumors in rodents also can disrupt
      thyroid hormone economy and, if sustained, increase the development of thyroid
      tumors in rats. A consistent finding with all of these goitrogens, be they either
      physiologic perturbations or xenobiotic chemicals, is the chronic hypersecretion
      of TSH, which by receptor-mediated events places the rodent thyroid gland at
      greater risk of developing tumors through a secondary mechanism of thyroid
      oncogenesis.

PMID- 7526406
TI  - Development of transgenic mouse models of skin carcinogenesis: potential
      applications.

PMID- 7526407
TI  - Carbamate analogues of tocainide.
AB  - A series of the new aminoalkyl esters of chlor-, methyl- and alkoxy carbanilates
      was synthesized. All the compounds prepared were found to exhibit antiarrhythmic
      activities comparable with those of mexiletine.

PMID- 7526408
TI  - Localization of nitric oxide synthase in the adult rat brain.
AB  - The distribution of the immunoreactivity to nitric oxide synthase has been
      examined from rostral to caudal areas of the rat central nervous system using
      light microscopy. Endogenous nitric oxide synthase was located using a specific
      polyclonal antiserum, produced against affinity purified nitric oxide synthase
      from whole rat brain, following the avidin-biotin peroxidase procedure.
      Immunoreactive cell bodies and processes showed a widespread distribution in the
      brain. In the telencephalon, immunoreactive structures were distributed in all
      areas of the cerebral cortex, the ventral endopiriform nucleus and claustrum, the
      main and accessory olfactory bulb, the anterior and posterior olfactory nuclei,
      the precommisural hippocampus, the taenia tecta, the nucleus accumbens, the stria
      terminalis, the caudate putamen, the olfactory tubercle and islands of Calleja,
      septum, globus pallidus and substantia innominata, hippocampus and amygdala. In
      the diencephalon, the immunoreactivity was largely found in both the hypothalamus
      and thalamus. In the hypothalamus, immunoreactive cell bodies were
      characteristically located in the perivascular-neurosecretory systems and
      mamillary bodies. In addition, immunoreactive nerve fibres were detected in the
      median eminence of the infundibular stem. The mesencephalon showed nitric oxide
      synthase immunoreactivity in the ventral tegmental area, the interpeduncular
      nucleus, the rostral linear nucleus of the raphe and the dorsal raphe nucleus.
      Immunoreactive structures were also found in the nuclei of the central grey, the
      peripeduncular nucleus and substantia nigra pars lateralis, the geniculate
      nucleus and in the superior and inferior colliculi. The pons displayed
      immunoreactive structures principally in the pedunculopontine and laterodorsal
      tegmental nuclei, the ventral tegmental nucleus, the reticulotegmental pontine
      nucleus, the parabrachial nucleus and locus coeruleus. In the medulla oblongata,
      immunoreactive neurons and processes were detected in the principal sensory
      trigeminal nucleus, the trapezoid body, the raphe magnus, the pontine reticular
      nuclei, the supragenual nucleus, the prepositus hypoglossal nucleus, the medial
      and spinal vestibular nuclei, the dorsal cochlear nucleus, the medullary
      reticular field, the nucleus of the solitary tract, the gracile and cuneate
      nuclei, the dorsal nucleus of the vagus nerve and the oral, interpolar and caudal
      parts of the spinal trigeminal nucleus. In the cerebellum, the stellate and
      basket cells showed immunoreactivity, which was also seen in the basket terminal
      fibres of the Purkinje cell layer. Isolated immunoreactive Purkinje cells were
      found in the vermis and parafloccular regions of the cerebellum. In the granular
      layer of the cerebellum, the granular cells and glomeruli were also
      immunoreactive. Numerous positive varicose nerve fibres and occasional neurons
      were also found in the lateral and interposed cerebellar nuclei.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7526409
TI  - [Adolescent and child anorexia: various possible common elements].
AB  - Based on their clinical experience, the authors investigate the possible links
      between early-age anorexia and adolescent anorexia. Although it is not common to
      find these two types of anorexia in the same person, the occurrence is found
      indeed. More often, anorexia at an early age has been described as occurring in
      offsprings of mothers who themselves had presented anorectic behaviors, either at
      an early age or in adolescence. The authors question the possible role of the
      psychopathology of mourning in the genesis of anorectic symptoms. They then
      proceed to some more general considerations on object relations observed in these
      cases. They suggest that a lack of integration of a satisfactory object relation
      may breed disturbances in relations and in symbolization of the type frequently
      observed in the semiology of early age or adolescent anorexia.

PMID- 7526410
TI  - Imitation and action in autism: a critical review.
AB  - This article considers the evidence for an imitative deficit in autism and for
      the possible role of deficiencies in the representation of actions. An argument
      is developed for the claim that the imitation problem is diagnostic of a basic
      information-processing rather than a social dysfunction. Reviews are offered of
      the empirical literature on gestural imitation in autism (and other developmental
      disorders) and the more anecdotal evidence for problems in the domain of action
      development in autism. An account that may help to integrate these areas is
      suggested, as are directions for future research.

PMID- 7526411
TI  - Impact of tumor stroma on expression of the tumor bed effect in R1H rat
      rhabdomyosarcoma.
AB  - The impact of intratumoral stroma on the expression of the tumor bed effect was
      studied in R1H rat rhabdomyosarcoma. For this, either R1H tumors growing in
      subcutaneous tissues (in situ) were irradiated at median volumes of 40 mm3 with a
      single exposure of 15 Gy (200 kVp X rays), or fresh tumor fragments or cloned
      tumor cells cultured in vitro were transplanted into subcutaneous tissue 2 days
      after preirradiation with 15 Gy. The tumor bed effect was evaluated by the time
      necessary for experimental tumors to grow from 0.1 cm3 to 10 cm3. When irradiated
      in situ, R1H tumors expressed a clear-cut tumor bed effect. The growth rate was
      decreased by a factor of 1.8 +/- 0.2 compared to controls. A significant decrease
      in growth rate by a factor of 1.7 +/- 0.2 was also observed when cultured tumor
      cells were transplanted into preirradiated tissue. However, when tumor fragments
      were transplanted into preirradiated sites, no significant decrease in growth
      rate occurred in two independent experiments (1.0 +/- 0.1; 1.2 +/- 0.2). Our
      results indicate that vessels originating from the intratumoral stroma can
      modulate the expression of the tumor bed effect in R1H tumors.

PMID- 7526412
TI  - Varying levels of radioprotection from the effects of JANUS neutrons in repair
      deficient xrs-5 hamster cells treated with azacytidine.
AB  - A series of cell lines have been generated from the radiation-sensitive Chinese
      hamster ovary line xrs-5 by treatment with azacytidine. Several of these lines
      have been shown to be resistant to gamma radiation. Survival curves have been
      generated for several of these lines and the parental lines after exposure to 0
      to 5 Gy of JANUS neutrons in the presence or absence of a 30-min pretreatment
      with the aminothiol radioprotector WR-1065. These studies were performed to
      determine whether the parental xrs-5 cell line was radioresistant to exposure to
      JANUS neutrons and whether reversion to a neutron-resistant phenotype correlated
      with recovery of aminothiol radioprotection. Exposure to 4 mM WR-1065 enhanced
      survival after exposure to neutron radiation for most "revertant" lines, although
      the increase in survival varied. The xrs-5 cell line was sensitive to JANUS
      neutrons and showed no protection by WR-1065. These data indicate that xrs-5
      cells are also sensitive to neutron radiation, that azacytidine-induced
      revertants for gamma-ray survival demonstrate the wild-type phenotype for
      survival after neutron exposure, and that the gene product that is defective is
      responsible for repairing only a small portion of neutron-induced damage.

PMID- 7526413
TI  - Determinants of in vivo MR imaging of slow axonal transport.
AB  - PURPOSE: To investigate specific surface characteristics of magnetic contrast
      agents based on a monocrystalline iron oxide nanoparticle (MION) that may
      determine their uptake and/or transport by axons. MATERIALS AND METHODS: MION
      were modified to have a range of surface charges or were covalently linked to
      wheat germ agglutinin (WGA), a neurotropic protein. Each agent was injected
      directly into the sciatic nerves or femoral arteries of rats (n = 22), and
      magnetic resonance (MR) images were obtained several days later. The imaging
      results then were correlated with results at postmortem histologic examination.
      RESULTS: Substantial uptake and/or transport by axons occurred only after
      intraneural injection and only if the agent had a strong surface charge or was
      covalently linked to WGA. The sciatic nerves appeared as uniformly hypointense
      structures having lengths proportional to the time from injection to imaging, and
      the calculated transport rates (4-7 mm/d) were consistent with slow axonal
      transport. Numerous Schwann cells and macrophages acquired large fractions of the
      injected agents and contributed substantially to the imaging results. CONCLUSION:
      Those characteristics of MION-based contrast agents that promote efficacy after
      intraneural injection may impede delivery to the nerve after intraarterial
      injection.

PMID- 7526414
TI  - Covered, expandable esophageal metallic stent tubes: experiences in 119 patients.
AB  - PURPOSE: To study fluoroscopic placement of covered expandable stent tubes in
      patients with esophagogastric strictures. MATERIALS AND METHODS: Under
      fluoroscopic guidance, 132 stent tubes were placed in 116 patients with malignant
      neoplasm; four, in three patients with benign lesions. All patients had aphagia
      or dysphagia to soft food or liquid. RESULTS: After placement (successful in 100%
      of cases), 93 (78%) of the patients could ingest solid food; 24 (20%), soft food.
      Complications in the 119 patients included blockage in 13, stent tube migration
      in 12, gastroesophageal reflux in nine, severe pain in nine, and delayed massive
      bleeding in four. Most major complications were managed by means of a balloon
      catheter, a second stent tube, or analgesics. One hundred four patients died 2-80
      weeks after stent placement. CONCLUSION: Treatment with placement of a covered
      expandable stent tube is effective in most patients with dysphagia due to
      malignant esophogastric strictures and is less effective in patients with benign
      strictures.

PMID- 7526415
TI  - Biopsy of inoperable pancreatic tumors does not adversely influence patient
      survival time.
AB  - PURPOSE: To determine the influence of pancreatic biopsy on the survival times of
      patients with inoperable tumors of the pancreas. MATERIALS AND METHODS: One
      hundred seventy patients were examined; results of histologic analysis confirmed
      pancreatic malignancy in 119. The biopsy and nonbiopsy groups were comparable for
      age, sex, the presence of liver metastases, and nodal status. RESULTS: No
      statistically significant difference was demonstrated between the survival time
      for the biopsy group (median, 23 weeks) and that for the nonbiopsy group (median,
      22 weeks). The estimated relative risk for death (biopsy group compared with
      nonbiopsy group) was 0.85 (95% confidence limits = 0.61, 1.18). CONCLUSION:
      Pancreatic biopsy does not appear to adversely influence survival time for
      patients with inoperable pancreatic tumors. Because histologic examination aids
      clinical management, biopsy should be part of the diagnostic work-up for patients
      with suspected inoperable pancreatic carcinoma.

PMID- 7526416
TI  - Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion
      permeability and transmitter systems.
AB  - In this review we have argued that corticosteroid hormones represent an endocrine
      signal that can influence neuronal communication. The steroids bind to
      intracellular receptors in the brain, resulting in slow effects that involve gene
      transcription, but they may also evoke rapid effects via membrane receptors. The
      signal carried by the corticosteroids is therefore divergent with respect to the
      dimension of space and time. Within the rat brain, at least two intracellular
      receptor subtypes, i.e. MRs and GRs, bind corticosterone. The affinity, density
      and localization of the MRs is different from the GRs, although the actual
      properties may vary somewhat depending on the condition of the animal. In
      general, due to the difference in affinity, low corticosteroid levels result in a
      predominant MR occupation, while higher steroid levels additionally occupy GRs.
      Recent studies indicate that predominant MR occupation is important for the
      maintenance of ongoing transmission in certain brain regions and for
      neuroprotection. By contrast, additional GR occupation (for a limited period of
      time) results in an attenuation of local excitability; yet, prolonged exposure to
      high steroid levels may become an endangering condition for neurons. Since
      predominant MR occupation on the one hand and additional GR occupation on the
      other hand induce different cellular actions, the ratio of MR/GR occupation is an
      important factor determining the net effect of corticosteroid hormones in the
      brain. How coordinated MR- and GR-mediated effects control neuronal communication
      under various physiological and pathological conditions will be a challenge for
      future research.

PMID- 7526417
TI  - Proton-induced current in neuronal cells.

PMID- 7526418
TI  - Modulation of ion channels by arachidonic acid.

PMID- 7526420
TI  - Distribution of calcitonin gene-related peptide-like immunoreactivity in the
      bovine conduction system: correlation with substance P.
AB  - The role of calcitonin gene-related peptide (CGRP) in the heart conduction system
      is unclear. In the present study, the distribution of CGRP in relation to that of
      substance P (SP) was examined in the bovine conduction system using
      immunohistochemical methods. Varicose nerve fibres showing CGRP-like
      immunoreactivity (LI) were frequently observed in the nerve fascicles, some of
      these fibres often also showing SP-LI. A few fibres exhibiting CGRP-LI were also
      observed in the intrinsic ganglia. In blood vessel walls and particularly in the
      conduction tissue, i.e., in association with the nodal cells and the Purkinje
      fibres, there were only a few varicose fibres showing both CGRP- and SP-LI,
      whilst there was a large number of varicose fibres showing only SP-LI. The
      observations show that the main morphologic correlate for the occurrence of CGRP
      effects in the bovine conduction system is varicose nerve fibres located in the
      nerve fascicles. The observations also suggest that CGRP has effects at the
      intrinsic ganglia and that SP predominates over CGRP in the innervation of blood
      vessel walls and the conduction tissue.

PMID- 7526421
TI  - Multiple molecular forms of tachykinins in rat spinal cord: a study comparing
      different extraction methods.
AB  - Various procedures for extraction at acid, neutral and alkaline pH were compared
      with regard to the yield of different tachykinins and tachykinin-like substances
      from rat spinal cord. Reverse phase high performance liquid chromatography (RP
      HPLC) and radioimmunoassay with various C-terminally directed tachykinin antisera
      and a newly developed N-terminally directed substance P (SP)-antiserum (SPN 1)
      were used. Antiserum SPN 1 fully reacts with SP-analogues modified at the C
      terminal end (SP free acid and SP-Gly-Lys) and also (77%) with SP(1-9) but not
      with C-terminal SP-fragments lacking 2 or more N-terminal amino acids. The
      highest levels of SP-like immunoreactivity (LI) and neurokinin A (NKA)-LI were
      measured after combined water and acetic acid extraction procedures. Also when
      measuring cholecystokinin-like immunoreactivity the highest level was obtained
      following this extraction procedure. RP-HPLC revealed a major component of SP-LI
      at the position of synthetic SP irrespectively of the extraction method and if
      the C- or N-terminally directed antiserum was used. Neutral water extracts
      contained a late eluting component detected with the C-terminally, but not with
      the N-terminally, directed antiserum. Acid and alkaline extracts, in contrast,
      contained components which could be detected with the N-terminally, but not with
      the C-terminally, directed SP-antiserum. Immunoreactive components eluting at the
      position of NKA and NKB were found in all types of extracts with NKA-, kassinin-
      and eledoisin-antisera. The NKB- and neuropeptide K (NPK)-components were more
      prominent in acid than in neutral and alkaline extracts. In conclusion, the
      present results indicate that rat spinal cord may contain molecular forms of
      tachykinin-like immunoreactivity in addition to those previously described and
      illustrate the importance of the choice of extraction method in immunochemical
      studies. Combined extraction in water and acetic acid appears to be a suitable
      method when the content of peptides with different chemical properties are to be
      measured in a tissue sample.

PMID- 7526419
TI  - Serotonine and suicide: a preliminary study concerning a sample of violent
      suicidal patients.
AB  - 1. A sample of patients having attempted to commit suicide by using violent
      methods (hanging, jumping) was investigated according to the following procedure:
      for each patient, some evaluative tests (the MADRS, the SCL 90 and an agressivity
      scale) were administered and DSM III diagnosis was provided as well as the
      therapeutical orientation. 2. The 5 HIAA' level was measured in the CSF soon
      after the suicide attempt except for patients with rachis fracture or exposed to
      a cerebral oedeme. 3. Results were compared to those of a control group composed
      with patients having operated with rachi-anesthesia for orthopedic surgery. 4.
      The preliminary results show that 5 HIAA' levels were lower for suicide patients
      except for one schizophrenic patient. 5. This study suggests the possible link
      between a low 5 HIAA' level in CSF and the clinical aspects of severe suicidal
      behaviour.

PMID- 7526423
TI  - [Reducing the number of amniocenteses in women older than 35 years using serum
      markers levels?].

PMID- 7526422
TI  - Nonorganic failure to thrive: developmental outcomes and psychosocial assessment
      and intervention issues.
AB  - Serious growth problems, such as Nonorganic Failure to Thrive (NFTT), place an
      infant/toddler at significant risk for poor developmental outcomes. Evidently, an
      NFTT child's malnutrition and subsequent poor growth and development are
      accentuated by a family context of impoverishment, dysfunctional relationships,
      inadequate education, and a dearth of developmentally enriching experiences. The
      purpose of this review is to describe NFTT, to present development outcomes, and
      to discuss psychosocial assessment and intervention issues relevant to this
      developmental disability of early childhood. An ideographic approach to case
      conceptualization, evaluation, and treatment is suggested to achieve successful
      developmental outcomes and to guide research endeavors.

PMID- 7526425
TI  - [Somatic gene therapy of mucoviscidosis. Several elements for a reflection on
      ethics].

PMID- 7526424
TI  - [The hypoplastic left heart syndrome. Initiation of a therapeutic program].
AB  - The hypoplastic left heart syndrome is a very severe congenital heart disease
      dependent on patency of ductus arteriosus in the newborn. The survival after
      neonatal period, without surgical treatment, is exceptional. Nowadays, there are
      basically two types of therapeutic procedures: Palliation with the Norwood
      operation and/or cardiac transplantation. Both methods have showed advantages and
      disadvantages; at present, there is not consensus of them. In our hospital, we
      have recently begun a medical-surgical therapeutic program for the management of
      neonates with hypoplastic left heart syndrome. Because of this, we report our
      little experience. We have treated three children in the last year: The first of
      them dead in the operating room; the second was exitus due to a sepsis two months
      after surgery, and the third, who is three-month-old now, remained well and was
      discharged to home.

PMID- 7526426
TI  - [Prospects of gene therapy in mucoviscidosis using viral infection of the airway
      epithelium].
AB  - Mucoviscidosis is the most common severe inherited autosomal recessive disease.
      Since the gene has been recognised (cystic fibrosis transmembrane conductance
      regulator gene) (CFTR) the technique of genetic transfer has been applied to the
      airway epithelium. The prospect for gene therapy to treat the consequences of
      bronchopulmonary mucoviscidosis is now evident. The in vitro introduction of the
      normal CFTR human gene in epithelial cells has been obtained using recombinant
      retrovirus, adenovirus and parvovirus rendered defective for replication. The
      abnormal bioelectric phenotype of the cells from patients with mucoviscidosis has
      been corrected. Of these, only adenovirus and parvovirus have been capable of
      assuring effective genetic transfer by direct introduction into the airways. This
      data has been considered sufficient to justify starting clinical trials in man
      with adenovirus; the preliminary results confirm the possibility of correcting
      the chloride transport. Nevertheless the observation of an immune response and
      secondary inflammation raises ethical questions relative to the safety of such
      trials. This observation justifies research into an alternative non-viral
      technique such as employing liposomes. The authors have made a review of the data
      which may be established as a basis for genetic therapy for mucoviscidosis.

PMID- 7526428
TI  - [Extraosseous Ewing's sarcoma with thoracic localization].
AB  - We report two cases of extraosseous Ewing's sarcoma revealed by large volume
      thoracic tumour lesions, occurring in a clinical context of an alteration in
      general health. The tumour mass was occupying the upper half of the left
      hemithorax, and was invading the thoracic wall posteriorly in the first case; it
      occupied the whole of the right hemithorax with invasion of the first three ribs
      in the second case. The first patient received five treatments with chemotherapy,
      using cyclophosphamide in association with adriamycin, which led to a partial
      response and was completed with surgical excision and a further five doses of
      chemotherapy using cyclophosphamide in association with etoposide. Subsequently
      radiotherapy was given. There was an unfavorable outcome, with recurrence in the
      13th month. The second patient received three courses of chemotherapy using
      cyclophosphamide in association with actinomycin D and vincristine, which allowed
      for an 80% reduction in the tumour volume. Surgical resection was then carried
      out, followed by five courses with the same chemotherapy protocol. Forty-two
      months after the diagnosis this patient remained in complete remission. These two
      cases enable us to stress the value of associating a chemotherapy protocol
      consisting of cyclophosphamide, actinomycin D and vincristine, with systemic
      surgical excision in tumours with a high potential for development.

PMID- 7526429
TI  - Evidence of cytokeratin expression in canine visceral glomerular epithelial cells
      in vivo.
AB  - Visceral glomerular epithelial cells (vGECs) originate from a mesenchymal
      blastema and transiently express cytokeratin during embryogenesis. There are no
      reports of cytokeratin expression in vGECs of mature, normal or damaged, human or
      other mammalian kidneys in vivo, but in vitro studies have provided evidence of
      the synthesis of cytokeratin in cultured vGECs. Cytokeratin expression was
      observed in vGECs in the damaged kidneys of four dogs with spontaneous renal
      diseases and, by using monoclonal antibodies, type 18 cytokeratin was identified.
      vGECs are apparently able to (re-) activate in vivo a mechanism for switching on
      the synthesis of cytokeratin in damaged glomeruli.

PMID- 7526427
TI  - [Neuropeptides of the nasal innervation and allergic rhinitis].
AB  - In the last decade, several neuropeptides have been localized in sensory,
      sympathetic and parasympathetic neurons of the upper and lower airways in animals
      and man. Tachykinins are sensory neuropeptides: after nasal allergen challenge in
      patients with allergic rhinitis, substance P is locally released and induces
      nasal obstruction. Like neurokinin A, another tachykinin of sensory C fibers,
      substance P induces an increase in vascular permeability and a recruitment of
      inflammatory cells. Thus, tachykinins partially mimic nasal response to antigen.
      Calcitonin gene-related peptide (CGRP) is another sensory neuropeptide and
      vasoactive intestinal peptide (VIP) is a neuropeptide localized to
      parasympathetic fibers. The distributions of CGRP and VIP fibers and of their
      binding sites, as well as their physiological effects described in other tissues,
      are consistent with a vasodilator effect. On the other hand, neuropeptide Y
      (NPY), a sympathetic neuropeptide, would seem to be a potent vasoconstrictor.
      Thus, nasal neuropeptides, and above all sensory neuropeptides, could play a role
      in the pathophysiology of allergic rhinitis.

PMID- 7526430
TI  - Paraganglioma of the lung--developed after exposure to nuclear radiation by the
      Tschernobyl atomic reactor accident?
AB  - A 36-year-old Russian patient had been exposed to severe nuclear radiation during
      the Tschernobyl accident and developed Cushing's syndrome in September 1991.
      After bilateral adrenalectomy a small centrally localized lung tumor in the left
      segment S6 was diagnosed, and the syndrome was correlated to primary lung cancer.
      Thoracotomy and resection of the segments S6 revealed a primary ACTH-producing
      lung tumor of the cell type of a paraganglioma. The patient lost his symptoms
      after curative tumor resection. The case is discussed under the aspects of tumor
      etiology, its clinical course and immunohistochemical findings.

PMID- 7526431
TI  - Metastatic choroidal abscess and choroidal neovascular membrane associated with
      Staphylococcus aureus endocarditis in a heroin user.
AB  - BACKGROUND: A 44-year-old man who was an intravenous heroin user developed
      multiple septic emboli, including a choroidal abscess in the macula and foot and
      skin infection after Staphylococcus aureus endocarditis. METHODS: Prompt
      administration of systemic oxacillin and gentamicin was prescribed for the
      endocarditis. RESULTS: One week after septic embolization to the choroid, a
      subfoveal, poorly-defined choroidal neovascular membrane with retinochoroidal
      anastomosis was noted at the site of active choroidal infection. CONCLUSION:
      Systemic antibiotic therapy successfully eradicated the choroidal infection,
      prevented progression to endophthalmitis, and improved visual acuity.

PMID- 7526432
TI  - [Age-related macular degeneration].

PMID- 7526433
TI  - [Polymerase chain reaction--principles and clinical relevance].
AB  - Molecular hybridization analyses and polymerase chain reaction (PCR) have
      substantially contributed to the diagnosis of infectious, genetic and malignant
      hepato-/gastroenterological diseases. While not generally informative, the
      detection of hepatitis-C-virus (HCV) RNA by PCR is at present the only means to
      demonstrate active HCV replication. Furthermore, PCR has for the first time
      allowed the identification of the infectious agent causing Morbus Whipple
      (Tropheryma whippleii), the noninvasive molecular detection of familial
      adenomatous polyposis (FAP) as well as of K-ras mutations in stool from patients
      with colorectal cancer. While in principle exquisitely sensitive and specific,
      PCR is a complex technique with a substantial risk and false-positive results,
      respectively. With a better understanding of the molecular pathogenesis, PCR
      based diagnostics will be of increasing clinical significance for the sensitive
      and early detection, prevention or curative therapy of hepato
      /gastroenterological diseases.

PMID- 7526434
TI  - [Defects in neural tube closure in the Vaud canton 1980-1992. The impact of
      prenatal diagnosis].

PMID- 7526435
TI  - [Enuresis in children: what we should know. What we should do].

PMID- 7526437
TI  - Premature ventricular contractions.

PMID- 7526436
TI  - Environmental noise and sleep--a study of arousals, cardiac arrhythmia and
      urinary catecholamines.
AB  - Nine adult subjects with documented cardiac arrhythmia were studied during 4
      nights of sleep in a laboratory. A sleep polygraph and single-channel
      electrocardiogram were recorded continuously throughout each night. After the 1st
      night's familiarization, the subjects were presented with 1 night each of 50
      calibrated aircraft or truck noise events. One other night was noise-free.
      Intervals containing noise and paired quiet intervals were examined for sleep
      stage at interval onset, number of sleep stage changes and ventricular premature
      contractions (VPCs). Overnight urinary catecholamines were also assayed. It was
      found that noise increased the likelihood of arousal responses to the same extent
      in all sleep stages (p < 0.05). Four subjects showed frequent VPCs during the
      experiment. These VPCs were significantly related to sleep stage (p < 0.05) but
      not to noise events. Excretion of urinary catecholamines did not differ between
      noise and quiet nights.

PMID- 7526438
TI  - FDA approved new drug bulletin: risperidone (risperdal).

PMID- 7526439
TI  - Bidirectional small-intestinal permeability in the rat to some common marker
      molecules in vitro.
AB  - BACKGROUND: The barrier properties of the small intestine were investigated by
      studying the bidirectional permeability to five commonly used marker molecules.
      METHODS: Proximal and distal small-intestinal segments from rats were mounted in
      diffusion chambers, and the permeation of the markers 3H-mannitol (Mw 182), 51Cr
      ethylenediamineteraacetic acid (Mw 341), [mercaptopropionic acid], D-arginine8]
      vasopressin (Mw 1069), fluorescein isothiocyanate (FITC)-dextran (mean Mw 3000),
      and inulin (Mw 5200) was measured across the mucosa in both directions. RESULTS:
      A generally increased inward (mucosa to serosa) and a decreased outward (serosa
      to mucosa) permeation of the markers was found in the proximal to distal
      direction. The inward permeability showed increasing regional differences with
      decreasing size of the markers. In the absence of the villous epithelium, removed
      by scraping the intestinal wall, 86% to 62% of the proximal and distal barrier
      was lost in the inward direction but only 14% to 26% in the outward direction.
      CONCLUSIONS: The intestinal epithelial barrier is more permeable in the outward
      than in the inward direction, and regional permeability differences exist in a
      size-dependent fashion. The results suggest two passage routes, one for the
      smallest molecule, mannitol, and a second for the larger markers in the present
      size range, both apparently different from the route for macromolecules such as
      intact proteins.

PMID- 7526440
TI  - Bile viscosity in patients with biliary drainage. Effect of co-trimoxazole and N
      acetylcysteine and role in stent clogging.
AB  - BACKGROUND: The main disadvantage of endoscopic insertion of an endoprosthesis is
      the tendency of the stent to clog after a few months. In this study we determined
      the role of bile viscosity in stent clogging. METHODS: Sixty patients were
      stented with 10 Fr 11-cm stents. The stents were electively removed after 2
      months, and a bile sample was obtained simultaneously. Bile viscosity was
      measured with a coaxial rotation viscometer. The influence of treatment with
      antibiotics and a mucolytic agent on viscosity was assessed in a randomized
      trial. RESULTS: Bile viscosity correlated significantly with DNA and total
      protein concentration. After treatment with either N-acetylcysteine or co
      trimoxazole a lower mean value of the viscosity was observed, but this was not
      statistically significant. There was no correlation between bile viscosity and
      the amount of sludge adhering to the stents. CONCLUSIONS: In most patients bile
      viscosity plays a limited role in stent clogging. Only in patients with
      excessively high viscosity do mucolytic agents or treatment with antibiotics seem
      to have a role.

PMID- 7526441
TI  - The antibody MY4 recognizes CD14 on porcine monocytes and macrophages.
AB  - Several monoclonal antibodies directed against the human CD14 antigen have been
      established. We now report that the antibody My4, but not LeuM3, reacts with
      porcine monocytes. Among porcine peripheral blood mononuclear cells (PBMC), 14.6%
      of the cells stain with the CD14 antibody My4, which is similar to the percentage
      obtained with the antiporcine monocyte antibody 74-22-15. Two-colour
      immunofluorescence reveals that My4 and 74-22-15 antigens are coexpressed on the
      same cells, and cell sorter-purified My4+ cells exhibit the morphology of
      monocytes. Whole blood analysis (which also shows staining of granulocytes)
      reveals that the average percentage of My4+ monocytes amongst all leucocytes is
      5.8% with 580 cells/microliters. Furthermore, porcine peritoneal macrophages (PM)
      and alveolar macrophages (AM), both stain for My4, with a four-fold lower level
      on AM. Treatment of cells with phosphatidylinositol-specific phospholipase C
      decreases My4 staining, but does not affect staining with antibody 74-22-15.
      Immunoprecipitation with the My4 antibody from surface labelled pig mononuclear
      cells demonstrates a 54 kDa band similar to human CD14, and Western blotting with
      pig serum demonstrates two bands similar to the alpha and beta forms of human
      soluble CD14. Finally, the My4 antibody is capable of blocking lipopolysaccharide
      (LPS)-induced interleukin-6 production in isolated PBMC. These data show that
      the My4 antibody recognizes genuine CD14 on porcine monocytes and macrophages.

PMID- 7526442
TI  - An in vitro model for the expansion of V gamma 9 delta 2 T lymphocytes during
      development.
AB  - The gamma/delta T lymphocytes represent a minority of T lymphocytes in human
      peripheral blood. Although there have been reports of reactivity against (myco-)
      bacterial antigens and heat shock proteins, their function and antigen
      specificity remain ill defined. The biological role of gamma/delta T cells has
      been related to functions within the 'first line of defense'. Similar to
      gamma/delta T lymphocytes in the T-cell compartment, CD5 positive B cells
      represent a small subset of B lymphocytes, which is thought to be involved in the
      maintenance of natural immunity and autoimmunity. We provide evidence for the
      cooperation of gamma/delta T cells and CD5 positive B cells in the proliferative
      response of gamma/delta T cells to bacterial antigens. Our data indicate a strong
      proliferation of V gamma 9 delta 2 T cells in response to gram-negative bacteria,
      which is dependent upon the presence of CD5 positive B-CLL or activated normal B
      lymphocytes. The selective stimulation of the V gamma 9 delta 2 subpopulation by
      gram-negative bacteria is also confirmed by analysis of different gamma/delta T
      cell clones. The interaction of gamma/delta T cells with activated B cells and
      gram-negative bacteria may prove to be a useful model similar to the expansion of
      the V gamma 9 delta 2 subpopulation during development. In addition, our in vitro
      system should provide new insights in the interaction of CLL B cells with the
      immune system and the antigens recognized by gamma/delta T cells.

PMID- 7526443
TI  - Immunostimulatory effect of thalidomide in normal C57BL/6 mice is compatible with
      stimulation of a highly connected central immune system.
AB  - Although thalidomide has been used with success in the treatment of increasing
      numbers of autoimmune diseases, the therapeutic effects have not been
      satisfactorily explained so far. We describe here some findings that may
      contribute to a better understanding of the immunomodulatory effects of this
      drug. Several immunological changes were observed after treating C57BL/6 mice
      with 3 mg of thalidomide. The numbers of natural IgM PFC against sheep red blood
      cells were increased in the spleen, and occasionally a dramatic oscillatory
      increase in the numbers of non-specific splenic IgM and IgG PFC was observed in
      these mice. However, these oscillatory increases were progressively lower, after
      two and three treatments with thalidomide at 20-day intervals. Furthermore, the
      absolute numbers of splenic CD5+ B and CD5- B lymphocytes were increased whereas
      depletion of CD4+ CD8+ cells in the thymus and of lymphoid cells in the bone
      marrow was seen after a single treatment with 3 mg of thalidomide. Taken
      together, these results suggest that thalidomide stimulates both peripheral and
      central immune systems and consequently enhances the connectivity of the central
      immune system.

PMID- 7526446
TI  - Neuromotor precursors of schizophrenia.
AB  - Previous research suggests that in addition to being a characteristic of
      schizophrenia, neuromotor dysfunction also predates the onset of the syndrome.
      The research reported here was intended to examine further the neuromotor
      development of children with preschizophrenia traits. This study is part of a
      larger "archival-observational" project that uses childhood home movies to
      explore the developmental precursors of schizophrenia. Group comparisons revealed
      a higher rate of neuromotor abnormalities in the preschizophrenia children when
      compared to their healthy siblings, preaffective disorder subjects, the healthy
      siblings of patients with affective disorder, and subjects from families with no
      mental illness. The preschizophrenia subjects also showed poorer motor skills
      when compared to their healthy siblings and preaffective disorder subjects. When
      diagnostic group comparisons were made within age spans, the group differences
      were significant only in the first 2 years of life. Post hoc analyses also
      revealed that the preschizophrenia subjects' neuromotor abnormalities occurred
      primarily on the left side of the body. The abnormalities included choreoathetoid
      movements and posturing of the upper limbs, similar to the motor signs described
      in earlier reports on diagnosed schizophrenia patients. The findings are
      discussed in light of their implications for the developmental origins of
      schizophrenia. Limitations of the study, including problems with sample
      representativeness and the reliance on observational data, are also discussed.

PMID- 7526447
TI  - Developmentally moderated expressions of the neuropathology underlying
      schizophrenia.
AB  - A gradually accumulating body of literature suggests that behavioral dysfunction
      precedes the onset of the schizophrenic syndrome by many years. Thus, a
      comprehensive neurodevelopmental model of schizophrenia must encompass these
      early manifestations of dysfunction as well as the postmorbid period. This
      article draws on previous research findings as well as recently proposed
      neurodevelopmental models to offer some further hypotheses about the
      neurodevelopmental process underlying the changing life-course manifestations of
      the diathesis for schizophrenia. It is proposed that normal maturational events
      in the central nervous system moderate the behavioral expression of a congenital
      neuropathology that affects subcortical regions of the brain that are part of
      multiple neural circuits. Specifically, it is suggested that the diathesis for
      schizophrenia involves a functional excess of dopamine activity in the basal
      ganglia that serves to disrupt these circuits. Findings from empirical research
      suggest a modal developmental trajectory for schizophrenia in which neuromotor
      dysfunction is most pronounced in early childhood and late in life, whereas
      florid psychotic symptomatology is most pronounced in late adolescence and early
      adulthood. The literature on normal central nervous system development suggests
      that the feedback circuit linking motor cortex with subcortical structures is
      maximally metabolically activated, relative to other circuits, early and late in
      the life course. Thus, subcortical dopamine excess may be predominantly expressed
      in motoric symptoms during these periods. In contrast, late adolescence and early
      adulthood are marked by low motor cortex metabolic activity relative to other
      cortical regions, in particular limbic and frontal regions. In addition, hormonal
      changes appear to result in a maximal activation of the dopamine system during
      this developmental period. Thus, it is hypothesized that during this period the
      neural circuitry abnormality will be primarily behaviorally expressed in
      psychotic symptoms. Some implications of the model for the study of movement
      abnormalities and psychotic symptoms are discussed.

PMID- 7526445
TI  - Prenatal origin of schizophrenia in a subgroup of discordant monozygotic twins.
AB  - Neuropathological, obstetrical, and epidemiological evidence increasingly suggest
      that some cases of adult-onset schizophrenia have prenatal or neonatal
      etiological roots. We evaluated the developmental histories of 23 monozygotic
      twin pairs discordant for schizophrenia to determine when they markedly and
      permanently began diverging from each other in motor skills or unusual behavior.
      Seven of the twins (30%) who later developed schizophrenia had become permanently
      different from their cotwins by age 5 years. The early divergence group differed
      from the others by multivariate tests (p = 0.002) for within-twin pair effects
      and by univariate tests for physical anomaly scores (p = 0.01), total finger
      ridge counts (p = 0.001), family history of psychosis (p = 0.004), and serious
      perinatal complications or low birth weight (p = 0.05). It is concluded that some
      cases of adult-onset schizophrenia are associated with prenatal events, which may
      include neurodevelopmental abnormalities or specific insults such as anoxia or
      infectious agents.

PMID- 7526444
TI  - The effects of thalidomide treatment on autoimmune-prone NZB and MRL mice are
      consistent with stimulation of the central immune system.
AB  - We describe here some immunomodulatory effects of thalidomide on autoimmune-prone
      mice. The highly increased synthesis of splenic IgM in NZB mice, of splenic and
      lymph node IgG of different subclasses in MRL/n mice, and of splenic and lymph
      node IgG1 in MRL/lpr mice was markedly inhibited by thalidomide treatment. After
      a single treatment with 3 mg of thalidomide, the following changes were observed
      in NZB mice: (i) an initial decrease in the numbers of large CD5+ microhigh, and
      in the numbers of total CD5+ micro-, CD5- microhigh, CD5+ microhigh lymphocyte
      populations of the pleural cavity followed by a late increase in the numbers of
      large cells of the three cell populations; (ii) a consistent increase in the
      numbers of a CD5low microlow pleural lymphoid population; (iii) a consistent
      reduction in the numbers of splenic large CD5+ B cells and an oscillatory
      increase in the number of cells with CD5- phenotype; (iv) a late reduction in the
      numbers of splenic total CD5+ B cells. These results are consistent with the
      notion that thalidomide controls a disease-associated expansion of B cells in
      autoimmune prone mouse strains through a stimulatory effect of the drug on the
      immune system.

PMID- 7526448
TI  - Serum soluble E-selectin levels in Kawasaki disease.
AB  - Serum sE-selectin levels in KD were tested. In the KD patients' sera during the
      acute phase, the levels of circulating sE-selectin were markedly elevated (27.5
      +/- 10.9 ng/ml) compared to 3.1 +/- 1.0 ng/ml in the control subjects (p <
      0.0001). The serum sE-selectin levels remained significantly elevated in the
      subacute phase (16.2 +/- 7.3 ng/ml; p < 0.005). The acute phase sE-selectin
      levels and TNF-alpha correlated well in a linear pattern (r2 = 0.64, p < 0.01).
      Also the acute phase sE-selectin levels and IL-6 were well correlated (r2 = 0.54,
      p < 0.05). The elevated serum sE-selectin levels in patients with KD provides
      additional evidence for the relationship between acute vasculitis and serum sE
      selectin.

PMID- 7526450
TI  - [Rehabilitation of hemiplegia patients].
AB  - The indications for a specific rehabilitation training programme for elderly
      stroke patients are discussed. Special symptomatology, such as hemi-anesthesia as
      a result of a damaged perceptual process, apraxia including apraxia of dressing,
      communication disorders and affective disorders are presented. The measures to be
      taken for effective rehabilitation in hospital, in an institution for the elderly
      or in the home care situation are indicated. In addition, the physician has to
      have marked ability for empathic comportment.

PMID- 7526449
TI  - [Results of surgical therapy in esophagus and cardia carcinoma].
AB  - Surgery for carcinoma of the esophagus and cardia represents potentially curative
      therapy in early stage of tumor. In the advanced stage of tumor palliation is the
      only remaining therapeutic aim. In a retrospective study covering the period 1984
      1992 we analyzed 51 patients who underwent surgery for esophageal or cardia
      cancer to determine whether palliation by surgery is feasible. We also analyzed
      morbidity and mortality of peri- and postoperative complications. In 88% we
      carried out standard esophagectomy consisting of abdomino-thoracic access,
      gastric interposition with thoracic anastomosis and extramucous pyloromyotomy. In
      the light of postresection histology, 53% of the operations were potentially
      curative (UICC stage I and II) [1], 47% palliative (UICC stage III and IV) [1].
      Perioperative 30-days mortality was nil, perioperative 30-days morbidity 11% (3
      patients developed pneumonia postoperatively, 2 patients with cervical
      anastomosis developed dehiscence of anastomosis which in both cases healed
      completely with conservative therapy, while a further patient with cervical
      anastomosis suffered persistent paralysis of the recurrent nerve. All patients
      were fully able to feed themselves at the time of discharge. 43% of patients had
      recurrent dysphagia and 24% underwent endoscopic dilatation. Three-year survival
      was 26%. From these results it may be concluded that esophageal resection
      represents either good palliation with low morbidity for the majority of patients
      with non-resectable carcinoma of the esophagus or potentially curative therapy
      with low morbidity in early stage of tumor.

PMID- 7526451
TI  - Is there a cognitive impairment in MND? A survey with longitudinal data.
AB  - Twenty-nine patients affected by motor neuron disease (MND) were investigated
      with the Raven Progressive Matrices, a test of logical non verbal intelligence,
      requiring neither motor nor verbal skills. The score distribution of the MND
      patients did not differ from that of 321 controls. Eleven of these patients were
      retested after a mean interval of 8.5 months. The resulting differences in the
      test scores showed that their intellectual performance had not worsened over
      time. Even allowing for the limitations posed by the use of a single test, these
      data add to the evidence against systematic cognitive involvement in MND.

PMID- 7526453
TI  - [The Helvetic whiplash trauma--nightmare of the legal profession?].
AB  - An appropriate management of medicolegal problems in the context of the so-called
      "whiplash-injury" calls for much effort from both sides, physicians and lawyers.
      Communication to the latter will be enhanced by medical statements, which are
      fulfilling the formal as well as the substantial criterias. Incomplete and/or
      incorrect medical information may end up in misleading conclusions by the lawyers
      and cause unnecessary difficulties in settlement. One out of the latest leading
      cases of the Swiss Federal Supreme Court, dealing with the aspect of causality,
      is stressed.

PMID- 7526452
TI  - [The structure of mnestic problems in multiple sclerosis: everyday memory
      performance and neuroradiologic findings].
AB  - 35 multiple sclerosis patients and 30 matched healthy controls were investigated
      for mnestic problems using a German everyday memory test. The objects were both
      the description of structural characteristics of disturbances and "ecological
      validity" to meet rehabilitative issues prospectively. In the MS group,
      impairments were found mainly in the memory domain under delayed recall
      conditions of complex material. The processing of these tasks may be especially
      sensitive against fiber tract lesions. While discrete lesions, mostly found in
      patients with relapsing-remitting courses, inconsistently lead to partial memory
      disturbances, global mnestic deficits are to be expected in confluent lesion
      patterns exceeding a critical "threshold of cerebral tolerance." The latter
      characterises mostly patients with chronic progressive disease courses.

PMID- 7526455
TI  - Acute reversible ataxo-myoclonic encephalopathy with flecainide therapy.
AB  - A 73 year-old patient with Wolff-Parkinson-White syndrome and paroxysmic
      supraventricular tachycardia developed an acute reversible encephalopathy within
      15 days of initiation of flecainide. The clinical picture was characterized by
      visual hallucinations, agitation, anxiety, but no disorientation, and a severe
      cerebello-myoclonic syndrome with total inability to stand up and walk, which was
      fully reversible on discontinuing the medication.

PMID- 7526454
TI  - Neurologic manifestations of Staphylococcus aureus infections. Analysis of 43
      patients.
AB  - We present an analysis of the neurologic manifestations of Staphylococcus aureus
      infections in 43 patients. Half of the infections whose source could be
      identified were nosocomial. The spectrum of neurological sequelae included
      meningitis, solitary and multiple intracerebral and epidural abscesses, cerebral
      ischemia and hemorrhage, acute encephalopathies, subdural empyemas, spinal
      abscesses, and radicular compression syndromes. In the majority of patients the
      course was severe and protracted and relapses were frequent. Mortality was high
      (28%), even with early diagnosis and treatment; diabetes mellitus, alcohol abuse,
      and chronic renal failure were unfavorable prognostic factors. In patients with
      abscess formation early surgical drainage improved the outcome. However, often
      treatment was complicated by sequestration at inaccessible foci and secondary
      dissemination. Combined antibiotic therapy with flucloxacillin and
      chloramphenicol may be the most successful antibiotic regimen.

PMID- 7526456
TI  - [Psychopathologic findings in subdural hematoma--consultation psychiatry as
      applied neuropsychiatry].
AB  - In the era of powerful neuroimaging devices, such as CCT and NMR, the diagnosis
      of intracranial mass lesions has been increasingly improved. Nevertheless, there
      are still delays in the detection of such disorders. Two case reports of patients
      with subdural haematoma are presented, in which the usefulness of a thorough
      psychopathological examination and the possible contribution of psychiatric
      consultation, understood as practical neuropsychiatry, in the detection of such
      disorders is demonstrated.

PMID- 7526457
TI  - [Apropos of Swiss research in psychogeriatrics. A critical analysis].
AB  - Psychogeriatrics is the general psychiatry of old age. It is closely related with
      the biological and human fundamental sciences and with the medical disciplines
      concerned with the care of old patients. Its issues are ubiquitous and also
      interest non psychiatrists, particularly geriatricians, internists, neurologists
      and psychologists. Therefore there is a risk for research to be spread out. As a
      medicine of synthesis, it must assert itself as a convergence point for the
      related branches. Its very vast field of research is confronted with particular
      methodological problems, like the chronological and biological age, the
      heterogeneity of the population, the polymorbidity. Psychogeriatrics is young and
      still requires an important involvement in the clinical tasks, in the medico
      social coordination and in the teaching to medical and paramedical circles. Rare
      are centers having the critical mass for developing good research with complete
      peace of mind, Switzerland is an example of this. An analysis of the 1992
      international literature shows a certain scattering of the psychogeriatric themes
      with a 50% predominance of papers devoted to dementias. In the future,
      psychogeriatrics must well limit its territory, particularly by developing
      services where care, teaching and research are harmonized.

PMID- 7526458
TI  - [Dance training and eating disorders].
AB  - Medical history, eating habits, weight, current symptomatology and EDI (Eating
      Disorders Inventory)-scores of 41 bulimic female patients with and without past
      training in dancing, who came for treatment to an outpatient clinic, were
      compared. It was found that both groups of patients were not different for age,
      age at beginning of bulimia, actual as well as minimal and maximal BMI (Body mass
      index), length and severity of symptomatology, frequency of bulimic behaviors,
      and scores on the subscales of the EDI, but it should be noted that these
      similarities might be in relationship with some methodological shortcomings.
      Considering the prevalence of bulimia nervosa in women and the high frequency of
      ballet and sports training in teenagers, some hypotheses about the possible
      influence of strenuous physical exercise in childhood on the symptomatology and
      some psychological traits in adults with anorexia nervosa, bulimia nervosa, or
      binge-eating disorder are presented. Further studies, including standardized
      scales and larger samples, are necessary.

PMID- 7526459
TI  - [The child and adolescent psychiatric clientele in the Zurich canton over two
      decades].
AB  - Data reflecting the clientele of the Child and Adolescent Psychiatric Service of
      the Canton of Zurich (Switzerland) spanning two decades between 1973 and 1993
      were analyzed. Referral patterns, age distribution, sex ratio in relation to age,
      and family background are reported on. In addition, the distributions of
      diagnoses according to ICD-9 and ICD-10, respectively, are compared. Furthermore,
      four main types of child and adolescent psychiatric disorders are documented with
      regard to age distribution. Finally, abnormal psychosocial situations according
      to the multiaxial scheme of classification are reported.

PMID- 7526460
TI  - [Social psychiatry today--what is it? Attempt at a clarification].
AB  - Related presumably to its heterogenous historical roots, the term "social
      psychiatry" is understood in divergent ways. The purpose of the present article
      is a clarification of its definition and contents on the base of current praxis
      in Switzerland and elsewhere. In the framework of a comprehensive psycho-socio
      biological understanding of the psyche, social psychiatry is defined as the
      domain of psychiatry which tries to understand and treat psychiatric disturbances
      in close relation with their social environment. Its main focus is in the
      community, where a whole range of innovative half-way institutions and
      therapeutic-rehabilitative methods have been developed during the last 10-20
      years. They are mainly indicated for patients suffering from disturbances of
      intermediate severity who no longer need continuous hospitalisation, but
      generally overtax the possibilities of private psychiatrists and traditional
      ambulatory services. The relative specificity of social-psychiatric approaches,
      research questions, therapeutic methods, infrastructures, targeted populations
      and community-related organisation of care speaks for a further systematic
      development of social psychiatry on the practical, and especially also on the
      academical level. This is also indicated from the economical point of view,
      because community-centered methods of treatment are considerably less expensive
      than full-time hospitalisations, according to recent cost-benefit -evaluations.

PMID- 7526461
TI  - [Interferon produced from trophoblast tissue of primates].

PMID- 7526462
TI  - [Regulation of alpha-fetoprotein gene expression].

PMID- 7526463
TI  - Determination of intrinsic transcription termination efficiency by RNA polymerase
      elongation rate.
AB  - Transcription terminators recognized by several RNA polymerases include a DNA
      segment encoding uridine-rich RNA and, for bacterial RNA polymerase, a hairpin
      loop located immediately upstream. Here, mutationally altered Escherichia coli
      RNA polymerase enzymes that have different termination efficiencies were used to
      show that the extent of transcription through the uridine-rich encoding segment
      is controlled by the substrate concentration of nucleoside triphosphate. This
      result implies that the rate of elongation determines the probability of
      transcript release. Moreover, the position of release sites suggests an important
      spatial relation between the RNA hairpin and the boundary of the terminator.

PMID- 7526464
TI  - Role of TCR zeta chain in T cell development and selection.
AB  - Signals mediated by the T cell receptor (TCR) are required for thymocyte
      maturation and selection. To examine the role of TCR zeta chain signals in
      development, TCR expression was restored in zeta-deficient mice with transgenic
      zeta chains that partially or completely lacked sequences required for signal
      transduction. The zeta chain played a role in thymic development by promoting TCR
      surface expression, but zeta-mediated signals were not essential because TCRs
      that contained signaling-deficient zeta chains promoted T cell maturation and
      transduced signals associated with thymic selection.

PMID- 7526465
TI  - Two binding orientations for peptides to the Src SH3 domain: development of a
      general model for SH3-ligand interactions.
AB  - Solution structures of two Src homology 3 (SH3) domain-ligand complexes have been
      determined by nuclear magnetic resonance. Each complex consists of the SH3 domain
      and a nine-residue proline-rich peptide selected from a large library of ligands
      prepared by combinatorial synthesis. The bound ligands adopt a left-handed
      polyproline type II (PPII) helix, although the amino to carboxyl directionalities
      of their helices are opposite. The peptide orientation is determined by a salt
      bridge formed by the terminal arginine residues of the ligands and the conserved
      aspartate-99 of the SH3 domain. Residues at positions 3, 4, 6, and 7 of both
      peptides also intercalate into the ligand-binding site; however, the respective
      proline and nonproline residues show exchanged binding positions in the two
      complexes. These structural results led to a model for the interactions of SH3
      domains with proline-rich peptides that can be used to predict critical residues
      in complexes of unknown structure. The model was used to identify correctly both
      the binding orientation and the contact and noncontact residues of a peptide
      derived from the nucleotide exchange factor Sos in association with the amino
      terminal SH3 domain of the adaptor protein Grb2.

PMID- 7526466
TI  - Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation
      channel.
AB  - Although several ion channels have been reported to be directly modulated by
      calcium-calmodulin, they have not been conclusively shown to bind calmodulin, nor
      are the modulatory mechanisms understood. Study of the olfactory cyclic
      nucleotide-activated cation channel, which is modulated by calcium-calmodulin,
      indicates that calcium-calmodulin directly binds to a specific domain on the
      amino terminus of the channel. This binding reduces the effective affinity of the
      channel for cyclic nucleotides, apparently by acting on channel gating, which is
      tightly coupled to ligand binding. The data reveal a control mechanism that
      resembles those underlying the regulation of enzymes by calmodulin. The results
      also point to the amino-terminal part of the olfactory channel as an element for
      gating, which may have general significance in the operation of ion channels with
      similar overall structures.

PMID- 7526468
TI  - Vinorelbine (Navelbine) in non-small cell lung cancer: future directions.
AB  - Randomized clinical trials of vinorelbine (Navelbine; Burroughs Wellcome Co,
      Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) as a single
      agent and in combination with cisplatin have demonstrated antitumor activity in
      patients with advanced non-small cell lung cancer (NSCLC). Administered as a
      single agent on a weekly schedule, the vinorelbine therapeutic profile compares
      favorably with other regimens currently used in palliative treatment of patients
      with advanced NSCLC. Vinorelbine is also being considered in other treatment
      settings as well: adjuvant treatment in stage I and II disease, and regimens with
      curative intent in stage IIIa and IIIb disease. Future directions for vinorelbine
      in the treatment of NSCLC are likely to be directed toward combination trials
      with other agents active in NSCLC. Current phase I-II trials, for example,
      combine vinorelbine with cisplatin, 5-fluorouracil/leucovorin, mitomycin-C,
      ifosfamide, carboplatin, and paclitaxel (Taxol; Bristol-Myers Squibb Co,
      Princeton, NJ). Some phase III trials are planned and some are under way.
      Vinorelbine has been a focus of interest in multimodality trials. A Canadian
      trial, for example, combined vinorelbine and cisplatin, followed by accelerated
      radiation. Results from all these trials can be expected to guide the further
      development of vinorelbine in adjuvant and neoadjuvant settings in NSCLC.
      Moreover, trials that are documenting the efficacy of vinorelbine in small cell
      lung cancer are just beginning.

PMID- 7526467
TI  - Vinorelbine (Navelbine)/carboplatin combination therapy: dose intensification
      with granulocyte colony-stimulating factor.
AB  - Treatment with platinum agents or the new vinca alkaloid vinorelbine (Navelbine;
      Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament,
      Paris, France) results in prolonged survival in patients with advanced non-small
      cell lung cancer (NSCLC). To determine whether a unique combination of these
      agents might enhance activity against NSCLC, a combination chemotherapy regimen
      consisting of intravenous carboplatin, administered on days 1 and 29, and
      intravenous vinorelbine, given once weekly, was evaluated. Because the dose
      limiting toxicity of both agents is myelosuppression, an additional study goal
      was to assess the ability of granulocyte colony-stimulating factor to alleviate
      hematologic toxicity and allow on-time, full-dose vinorelbine therapy. To this
      end, a phase I/II study was begun. Phase I of the study included 22 patients (15
      men and seven women) with a median age of 63 years (age range, 39 to 77 years)
      who had stage IV NSCLC and no prior chemotherapy. Phase I consisted of 28-day
      cycles in which intravenous carboplatin was administered at an area under the
      curve of 7 by the Calvert formula, dose range 350 to 450 mg/m2, and intravenous
      vinorelbine was administered weekly. Granulocyte colony-stimulating factor was
      administered if dose-limiting neutropenia developed. Four cohorts of patients
      were studied, ranging from those who received no vinorelbine to those who
      received drug doses of up to 30 mg/m2. Patients were able to tolerate the highest
      dose of vinorelbine, but the majority required granulocyte colony-stimulating
      factor support to do so. No novel toxicities were observed in patients treated
      with the combination of carboplatin and vinorelbine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7526469
TI  - Granulocyte colony-stimulating factor and amifostine (Ethyol) synergize to
      enhance hemopoietic reconstitution and increase survival in irradiated animals.
AB  - The reported studies tested whether amifostine could be used to protect
      hemopoietic stem cells, which, after irradiation, could be stimulated by
      granulocyte colony-stimulating factor (G-CSF) to proliferate and reconstitute the
      hemopoietic system. Female C3H/HeN mice were administered amifostine (Ethyol, US
      Bioscience, Inc, West Conshohocken, PA) (200 mg/kg intraperitoneally 30 minutes
      before cobalt-60 irradiation and G-CSF (125 micrograms/kg/d subcutaneously from
      days 1 to 16 after irradiation. Saline, G-CSF, amifostine, and amifostine plus G
      CSF treatments resulted in LD50/30 values of 7.85 Gy, 8.30 Gy, 11.30 Gy, and
      12.85 Gy, respectively. At these LD50/30 values, the dose reduction factor of
      1.64 obtained in combination-treated mice was more than additive between the dose
      reduction factors of G-CSF-treated mice (1.06) and amifostine-treated mice
      (1.44). Bone marrow and splenic multipotent hemopoietic stem cell and granulocyte
      macrophage progenitor cell recoveries, as well as peripheral white blood cell,
      platelet, and red blood cell recoveries were also accelerated most in mice
      treated with amifostine plus G-CSF. These studies demonstrate that
      therapeutically administered G-CSF accelerates hemopoietic reconstitution from
      amifostine-protected stem and progenitor cells, increasing the survival-enhancing
      effects of amifostine, and suggest that classic radioprotectants and recombinant
      hemopoietic growth factors can be used in combination to reduce the risks
      associated with myelosuppression induced by radiation or radiomimetic drugs.

PMID- 7526471
TI  - [Microinjection of opioid antagonist into periaqueductal gray blocks formalin
      induced alterations of substance P in spinal dorsal horn].
AB  - Using formalin injected into the rat's hind paw as nociceptive stimulation, the
      effect of naloxone and beta-endorphin (beta-EP) antiserum microinjected into the
      periaqueductal gray (PAG) on the level of substance P like immunoreactivity
      (SPLI) of the spinal dorsal horn was observed. After formalin injection, a
      significant increase in SPLI was found as compared with the control (P < 0.01).
      After naloxone or beta-EP antiserum microinjection, SPLI level in the dorsal horn
      was decreased (P < 0.05). It is thus suggested that nociceptive stimulation
      induce the release of beta-EP in the PAG, which, in turn, modulate SP release in
      the spinal dorsal horn.

PMID- 7526470
TI  - [Semiquantitative detection and application about the expression of nitric oxide
      synthase gene].
AB  - Using the Reverse Transcription (RT)-Polymerase Chain Reaction (PCR) method of
      Martin (1993) for semiquantitation determinating of NOS gene, it was found that
      NOS mRNA is not only existed in brain, but also distributed extensively in heart,
      kidney, lung and liver. Among of them, NOS mRNA levels were highest in the brain,
      followed in descending order by kidney, heart. In addition to endothelial cell,
      NOS gene was also highly expressed in smooth muscle cells, suggesting that they
      may be an important site of NOS in organism. Furthermore, NOS mRNA levels were
      found to decrease significantly in brain, kidney, liver and smooth muscle cell in
      spontaneous hypertensive rat. These data suggest that pathogeny of hypertension
      may be related to low expression of NOS gene in these tissues.

PMID- 7526472
TI  - Christ as a pharmacist: medical symbols in German devotion.
AB  - The author reports on two German publications [1,2] about the metaphoric use of
      medicines in Christian devotional literature and art in German society (16th to
      19th century). Christ is depicted as a pharmacist dispensing 'medicines' which
      contain Christian virtues and symbols.

PMID- 7526473
TI  - Studies on the effect of translocation of chemical insecticides in Eicchornia
      host plant on Mansonia mosquitos--a potential control method.
AB  - A novel method for the control of Mansonia larvae was developed and tested. In
      this method, foliar absorption and translocation of a chemical insecticide,
      monocrotophos, a known systemic insecticide was studied in the Eicchornia plant.
      Acetone solution of the insecticide was painted onto leaves of the plant. At
      daily intervals, stems were severed and divided into equal sections which were
      introduced into bowls. Larvae of Aedes aegypti were tested for the presence of
      monocrotophos. It was found that translocation of the insecticide occurred at
      different rates in the stems and in some plants the chemical was also released
      into the surrounding water. Based on these results, 2 insecticides namely,
      monocrotophos and temephos were painted onto leaves of the host plant and their
      translocation to the root and water environment was examined by testing with
      Mansonia and Aedes aegypti larvae. The results again confirmed the translocation
      process and it was found that the insecticides were secreted into the surrounding
      water, thereby killing the larvae. However, in leaves painted with permethrin
      (synthetic pyrethroid) or flufenoxuron (chitin synthesis inhibitor), such a
      process was not detected. The potential of this new concept in Mansonia larval
      control is examined.

PMID- 7526475
TI  - Cost effectiveness in the management of benign prostatic hyperplasia: Italian
      data.
AB  - Several works in literature demonstrate that in some countries the economic
      considerations are as important as the clinical aspects of a disease; economic
      evaluation may be of help for decision making. The exact cost of the diagnosis
      and treatment of benign prostatic hypertrophy (BPH) patients is difficult to
      estimate. The total number of males in Italy is 27,982,144 (1991 data). In the
      last year 2,200,000 patients have been treated for BPH in Italy (surgically and
      pharmacologically); the overall cost for the therapy of BPH exceeded 46 million
      dollars per year. Currently surgery represents the standard treatment of BPH. In
      the USA alone over 350,000 surgical procedures are performed annually. In USA the
      cost per TURP is 12,000 dollars. In Italy the minimum direct cost is 3681
      dollars; in most cases, however, the cost per TURP is over 5000 dollars. It is
      estimated that about 80% of patients with micturion problems prefer an
      alternative treatment before surgery. In our country 4,338,000 diagnoses of BPH
      have been performed in 1991. The number of prescriptions for BPH has been
      4,867,000 and the number of drugs per prescription 1.16. It may be of interest to
      compare costs associated with different pharmacological therapies for BPH.
      Considering the direct costs, it has been estimated that the cost of 1 year's
      treatment with finasteride is 1833 dollars, while that of 1 year with plant
      extracts is 1151 dollars. The existing literature is deficient in defining the
      cost related to the therapeutical options for BPH.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7526474
TI  - Experimental lumbar radiculopathy. Immunohistochemical and quantitative
      demonstrations of pain induced by lumbar nerve root irritation of the rat.
AB  - OBJECTIVE: A series of experiments were designed to develop and validate an
      animal model of lumbar radiculopathy. More specifically, these investigations
      introduced a model of chronic neuropathic pain in the rat associated with
      clinically relevant lumbar nerve root trauma and evaluated the ability of the
      model to effect symptoms and begin to understand the underlying neurochemical and
      neurophysiologic factors associated with these neurologic abnormalities. SUMMARY
      OF BACKGROUND DATA: A search of the literature suggested that these studies were
      a first attempt to distinguish and elucidate an experimental lumbar
      radiculopathy. METHODS: Two basic approaches to nerve trauma were considered,
      direct damage to the nerve via compression, and introduction of foreign materials
      in proximity to the nerve root that might cause irritation and inflammation
      leading to chronic symptoms. Ligature around the nerve (i.e., surrounding the
      nerve with a suture) was considered a plausible irritant that might behave in an
      animal model in a similar way that nerve root entrapment, often observed in HNP
      and stenosis cases, might function in humans. Further, varying levels of
      irritation was modeled by using 4-0 silk as a mild and 4-0 chromic gut as a more
      harsh irritant. STUDY DESIGN: Five distinct treatments of the nerve roots were
      investigated initially: 1) a sham intervention, where the surgery simply exposed
      the nerve roots and dorsal root ganglion followed by standard closing procedures;
      2) nerve root clipping, where the nerve roots were clipped with a microhemoclip;
      3) 4-0 silk ligature, where two loose ligatures of 4-0 silk were placed around
      the nerve roots; 4) 4-0 chromic gut 1, where one loose ligature of 4-0 chromic
      gut was placed around the nerve roots; and 5) 4-0 chromic gut 2, where four 0.3
      cm pieces of 4-0 chromic gut were laid adjacent to the nerve roots and secured by
      two loose ligatures of 4-0 chromic gut. ANOVA techniques were used to test for
      differential effects across time for the five treatment groups in terms of animal
      function and biochemistry in the DRG. RESULTS: Rats treated with chromic gut
      ligature in large quantity demonstrated differential patterns of results on the
      injured and noninjured sides consistent with a lumbar radiculopathy. The injured
      side demonstrated significantly worse thermal hyperalgesia related to neuropathic
      pain (P < 0.0001); initial mechanical hypoalgesia (P < .001), and motor
      dysfunction (P < .001) resolving within 2 weeks; significantly increased c-fos
      counts (P < .0001) 2 weeks postoperatively, which showed a consistent trend
      toward baseline and return to baseline by 12 weeks; significantly greater and
      highly increased VIP concentrations in the dorsal root ganglia 2 weeks
      postoperatively (P < .0001) that did not resolve or tend towards baseline after
      12 weeks of follow-up in conjunction with a trend toward VIP depletion in the
      spinal cord 2 weeks postoperatively that did resolve to baseline until a 12-week
      concentration indicated a significant increase in concentration (P < .002).
      Quantitative and qualitative changes in c-fos and VIP, correlated with the
      patterns of behavior and function. Thus, for the first time, evidence to link
      outcome behaviors and function with underlying neurochemical processes is
      suggested. CONCLUSIONS: When the same apparent conditions can be demonstrated in
      some situations to be causing pain and in other situations to be independent of
      pain, some additional factor or factors not considered in the original
      investigations may be mediating the outcome. Neurochemical consequences of nerve
      root irritation provide a theoretical framework for hypothesizing about various
      types of mediating events that might explain how similar apparent pathology might
      reasonably lead to different predictions about behavior consequences of the
      pathology.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7526476
TI  - [The clinical picture and therapy of malignant pleural mesothelioma].
AB  - BACKGROUND: In the general population malignant pleural mesothelioma is an
      uncommon tumor with an average annual incidence of 15 cases per million. Its
      biological behavior is characterized by an infiltrating and aggressive growth.
      Median survival ranges between 6 and 12 months. There are different therapeutic
      modalities (surgical treatment, radiotherapy, chemotherapy), which are used alone
      or in combination to influence the poor outcome of pleural mesothelioma. PATIENTS
      AND METHODS: We report about 7 of our own cases, treated with surgery and
      radiotherapy (4) or with a combination of surgery, radiotherapy and chemotherapy
      (3) and discuss the clinical aspects, diagnosis and the different ways of
      treatment of malignant pleural mesothelioma and its influence on survival.
      RESULTS AND CONCLUSION: The extrapleural pleuropneumonectomy should be reserved
      to patients with stage I disease. Radical operation here offers some prospect of
      long-term survival. Palliative surgery such as pleurectomy is the treatment of
      choice for extended disease. Radiotherapy using doses between 45 and 50 Gy is
      useful in a palliative setting. Anthracyclin or cisplatin based chemotherapy may
      be helpful in cases with disseminated disease. Prospective trials are necessary
      to further clarify the role of multimodality treatment programs for malignant
      pleural mesothelioma.

PMID- 7526478
TI  - [Anesthesia--when Simon and Signe were anesthetized].

PMID- 7526477
TI  - Influence of chlorpromazine, bleomycin and WR-2721 singly or in combination on
      the formation of radiation-induced micronuclei in mice bone marrow.
AB  - BACKGROUND/AIM: Radiotherapy of tumors is often accompanied by inadvertant side
      effects on the normal tissues after completion of the treatment, which may later
      on result in the development of secondary neoplasia. Aim was to investigate the
      effect of combination of radiosensitizing agents in combination with a
      radioprotector on the frequency of micronuclei in mouse bone marrow and to find
      out whether the administration of combination of radiosensitizing agents in
      combination with a radioprotective drug before irradiation will offer any
      significant advantage over the drugs used singly. MATERIALS AND METHODS: Female
      BALB/c mice were divided into 8 groups according to the treatment they received
      viz. 1. DDW (double distilled water), 2. chlorpromazine (CPZ) 10 mg/kg body
      weight, 3. CPZ 15 mg/kg body-weight 4. bleomycin (BLM), 5. WR-2721, 6. CPZ (10
      mg) + WR-2721, 7. CPZ (15 mg) + WR-2721, 8. BLM + WR-2721. After 30 min of drug/s
      administration the animals were exposed to either 0 or 4 Gy of 60Co g-radiation.
      The animals were killed at 24 h post-irradiation by cervical dislocation and the
      micronuclei were prepared according to the method described by Jagetia [17].
      RESULTS: The administration of CPZ (10 or 15 mg) alone increased the frequency of
      micronuclei significantly when compared to the DDW treatment. The exposure of
      mice with 4 Gy resulted in a significant increase in the frequency of micronuclei
      compared to the concurrent control groups. The frequency of micronuclei increased
      significantly in CPZ (15 mg) and BLM + irradiated groups. However, treatment with
      WR-2721 before irradiation reduced the frequency of micronuclei by approximately
      50% of the DDW + irradiated group. A further reduction in the frequency of
      micronuclei was observed when WR-2721 was combined with CPZ (10 and 15 mg) before
      irradiation. A combination of BLM with WR-2721 also resulted in a nonsignificant
      reduction in the frequency of micronuclei.

PMID- 7526479
TI  - [Nursing in a surgical short-stay unit].

PMID- 7526480
TI  - Results of chemotherapy in 30 AIDS patients with symptomatic pulmonary Kaposi's
      sarcoma.
AB  - BACKGROUND: The aim of this study was to report the effects of a three-drug
      chemotherapy regimen in patients with symptomatic AIDS-related pulmonary Kaposi's
      sarcoma and to analyse prognostic factors for survival. METHODS: Thirty
      consecutive HIV seropositive patients with respiratory symptoms and proven
      pulmonary Kaposi's sarcoma were treated with the same therapeutic regimen
      comprising adriamycin (30 mg/m2), bleomycin (10 mg/m2), and vincristine (2 mg)
      administered intravenously once every four weeks. RESULTS: Two patients died
      during the first course of chemotherapy. In the other 28 cases dyspnoea improved
      and Pao2 rose despite minimal (n = 17) or no (n = 11) improvement in the chest
      radiographic appearance. The median survival from the beginning of chemotherapy
      was 6.5 months. Poor prognostic factors for survival were: (1) absence of
      cutaneous Kaposi's sarcoma; (2) previous opportunistic infection; (3) CD4 cell
      count < 100/microliters; (4) leucocytes < 3500/microliters; (5) haemoglobin < 10
      g/dl; and (6) absence of radiological response. Of the 28 patients 24 experienced
      at least one episode of neutropenia which was associated with bacterial infection
      in 16 cases. CONCLUSIONS: Chemotherapy may improve respiratory impairment in
      patients with extensive pulmonary Kaposi's sarcoma but the outcome remains poor.
      The efficacy of chemotherapy may be limited by neutropenia.

PMID- 7526482
TI  - Effect of G-CSF on the haemostatic system.

PMID- 7526481
TI  - Low-affinity material does not contribute to the antithrombotic activity of
      Orgaran (Org 10172) in human plasma.
AB  - Orgaran is a LMW heparinoid composed of heparan sulphate (83% w/w) of which 4-5%
      has high affinity for antithrombin, dermatan sulphate (12% w/w) and chondroitin
      sulphate (5% w/w). To examine the contribution of the low-affinity fraction to
      Orgaran's antithrombotic activity we have quantitated the binding of plasma
      proteins to Orgaran and its component fractions in whole, hirudin-anticoagulated
      human plasma. Antithrombin, largely bound to the high-affinity fraction, and
      histidine-rich glycoprotein, interacting with low-affinity components, were the
      dominant proteins bound to Orgaran. Vitronectin, fibrinogen, fibronectin, heparin
      cofactor II, and apolipoprotein B were also detected in small amounts. The ratio
      of bound antithrombin, histidine-rich glycoprotein and vitronectin to GAG was
      negatively correlated with the Orgaran concentration in plasma, implying that the
      efficacy of Orgaran may not be linearly related to dose. Binding of antithrombin
      to the high-affinity fraction was not decreased by other plasma proteins or
      affected by addition of low-affinity material. Moreover, the antithrombin and
      anti-factor Xa activities of the high-affinity material were unaltered by low
      affinity GAGs. On the basis of our results we conclude that the low-affinity
      material does not contribute to the antithrombotic activity of Orgaran by binding
      non-anticoagulant plasma proteins and releasing the high-affinity chains to
      interact with antithrombin and its target proteinases.

PMID- 7526483
TI  - Circulating endothelial cell/leukocyte adhesion molecules in atherosclerosis.
AB  - Soluble adhesion molecules E-selectin, intercellular adhesion molecule (sICAM)
      and vascular cell adhesion molecule (sVCAM) were measured alongside von
      Willebrand factor (vWf) in 40 patients with peripheral vascular disease (PVD), 43
      with ischaemic heart disease (IHD) and in equal numbers of age and sex matched
      asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0008)
      and in patients with PVD (p = 0.0001) relative to their respective controls but
      levels did not differ between the two patient groups. Raised sICAM was found in
      both PVD (p = 0.0003) and IHD (p = 0.0059) compared to their respective controls
      and was higher in PVD than in IHD (p = 0.0088). In the subjects taken as a whole,
      there was no correlation between vWf and sICAM. Levels of soluble E-selectin and
      sVCAM did not differ in patients or controls. These data suggest that soluble
      ICAM may be useful as an index of endothelial cell activation in clinical
      manifestations of atherosclerosis.

PMID- 7526484
TI  - High dose aprotinin reduces prothrombin and fibrinogen conversion in patients
      undergoing extracorporeal circulation for myocardial revascularization.

PMID- 7526485
TI  - Study of different human and animal thromboplastins with human factor VIIa in the
      presence of aprotinin.

PMID- 7526486
TI  - Generation and characterization of a human monoclonal IgG antibody specific for
      HLA-B12.
AB  - We describe here the generation and characterization of a human monoclonal IgG
      antibody (UL/F14) specific for HLA-B12. The antibody is suitable for complement
      dependent lysis on lymphoblastoid cell lines and stimulated peripheral blood
      mononuclear cells. UL/F14 competes for antigen binding with an HLA-B12 human
      monoclonal IgM antibody and with a specific alloantiserum. Protein chemistry
      shows that the monoclonal antibody UL/F14 can precipitate solubilized HLA-B12
      molecules.

PMID- 7526487
TI  - Effect of mercuric chloride on macrophage-mediated resistance mechanisms against
      infection with herpes simplex virus type 2.
AB  - Macrophages play an important role in the early, nonspecific resistance to
      infection with herpes simplex virus. Mercuric chloride (HgCl2) accumulates in
      macrophages and has in certain concentrations a marked influence on the
      functional capacity of these cells. Therefore the influence of HgCl2 on
      resistance to generalized infection with herpes simplex virus type 2 (HSV-2) in
      mice and its effect on the HSV-2-induced activation of macrophages in vitro was
      examined. Mice injected intraperitoneally with HgCl2 24 h before infection with
      HSV-2 had more than 100 times higher virus titres in the liver 4 days after
      infection than mice not receiving any mercury. HgCl2 exerted a toxic effect on
      macrophages in vitro, which was especially pronounced during their adherence.
      Macrophages infected with HSV-2 were activated for an enhanced respiratory burst.
      This activation was abolished by treatment of the cells for 24 h with relatively
      low concentrations of HgCl2, resulting in macrophages with a potential to react
      with a respiratory burst comparable to that of uninfected cells. The HSV-2
      induced activation of macrophages is mediated through the production and
      synergistic interaction of interferon-alpha/beta and tumour necrosis factor-alpha
      in an autocrine manner. The ability of these cytokines to activate macrophages
      and to interact synergistically was not affected by mercury. However the
      production by macrophages of both cytokines during the HSV-2 infection, but
      especially interferon-alpha/beta, which is essential for the activation, was
      reduced at low concentrations of HgCl2. Collectively these data indicate that
      mercury, by interfering with the early macrophage-production of cytokines,
      disables the early control of virus replication, leading to an enhanced
      infection.

PMID- 7526488
TI  - Graded bioassay for demonstration of brain rescue from experimental acute
      ischemia in rats.
AB  - BACKGROUND AND PURPOSE: This study explored the correlation between duration of
      focal ischemia and infarct volume in spontaneously hypertensive rats as a measure
      of outcome after neuroprotective intervention. METHODS: We used 2,3,5
      triphenyltetrazolium chloride staining to discriminate infarcted tissue and
      calculate infarct volume 24 hours after temporary tandem common carotid/middle
      cerebral artery occlusion lasting 5 to 150 minutes. We used a graded bioassay
      described by logistic function and executed by computer program (ALLFIT) to
      evaluate changes in infarct volume after increasing durations of ischemia. The
      method allowed us to calculate the maximal infarct volume (Volmax) and the
      duration of ischemia before reperfusion producing half-maximal infarct size
      (T50). Hypothermia and the N-methyl-D-aspartate antagonist CNS-1102 begun after
      the onset of ischemia were tested for their ability to reduce Volmax and prolong
      T50 as analyzed by ALLFIT. RESULTS: Volmax was 180.6 +/- 22.4 mm3 and T50 was
      45.9 +/- 5.8 minutes in control rats. Hypothermia (30 degrees C) applied during
      ischemia reduced Volmax by 66 mm3 and extended T50 by 50% (P < .05 for each
      comparison). CNS-1102, like hypothermia, extended T50 by 44% but did not have an
      effect on Volmax. CONCLUSIONS: Analysis of the changes of infarct size after
      increasing durations of ischemia indicates that although both were protective,
      the two treatments tested may exhibit different profiles of efficacy. This method
      of analyzing ischemia-induced damage may be very sensitive for studying the
      efficacy and possible clinical use of neuronal protective therapies for
      hyperacute stroke.

PMID- 7526489
TI  - Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following
      transient focal ischemia in cats.
AB  - BACKGROUND AND PURPOSE: We tested the hypothesis that administration of the
      competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 17742 (2R,4R,5S
      [2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid]) during transient focal
      ischemia affects early postischemic brain injury. METHODS: Halothane-anesthetized
      cats underwent 1 hour of left middle cerebral artery occlusion plus 4 hours of
      reperfusion. Control cats received saline (n = 7). Experimental cats were treated
      with NPC 17742 at a dose of 5 mg/kg IV from 45 minutes of ischemia to 15 minutes
      of reperfusion and 2.5 mg/kg per hour for 4 hours of reperfusion (NPC-5; n = 7)
      or 50 mg/kg from 45 minutes of ischemia to 15 minutes of reperfusion and 25 mg/kg
      per hour for 4 hours of reperfusion (NPC-50; n = 5). RESULTS: Microsphere
      determined blood flow to the ipsilateral inferior temporal cortex and caudate
      nucleus decreased to the same extent during ischemia and recovered to the same
      extent during reperfusion in the three groups. Triphenyltetrazolium-determined
      injury volume of ipsilateral cerebral hemisphere (saline, 24 +/- 8%; NPC-5, 4 +/-
      2%; NPC-50, 5 +/- 2% of hemisphere; mean +/- SE) and caudate nucleus (saline, 72
      +/- 6%; NPC-5, 37 +/- 10%; NPC-50, 26 +/- 4%) was less in cats treated with both
      doses of drug compared with cats treated with saline. Recovery of somatosensory
      evoked potential amplitude was incomplete and similar in all groups (saline, 36
      +/- 14%; NPC-5, 58 +/- 8%; NPC-50, 51 +/- 15% of baseline). CONCLUSIONS: These
      data indicate that activation of NMDA receptors plays an important role in the
      mechanism of acute injury in both cortex and caudate after 1 hour of transient
      focal ischemia in the cat. Because NPC 17742 afforded protection when
      administered at the end of ischemia and during reperfusion, NMDA receptor
      activation during reperfusion may contribute to the progression of injury in
      ischemic border regions.

PMID- 7526490
TI  - Nitric oxide promotes arteriolar dilation during cortical spreading depression in
      rabbits.
AB  - BACKGROUND AND PURPOSE: Pial arterioles transiently dilate during cortical
      spreading depression (CSD), although the mechanisms are unclear. We tested the
      hypothesis that increased production of nitric oxide (NO) promotes arteriolar
      dilation. METHODS: Urethane-anesthetized rabbits were equipped with cranial
      windows, and the diameter (reported in micrometers) of a pial arteriole was
      determined via intravital microscopy. In each rabbit, a baseline CSD was elicited
      by microapplication of KCl onto the cortex, and resultant pial arteriolar
      dilation was measured. Either 100 mumol/L N omega-nitro-L-arginine methyl ester
      (L-NAME) or 50 mumol/L NG-nitro-L-arginine (L-NA), both competitive NO synthase
      inhibitors, was then applied to the brain surface. A CSD was elicited as before.
      The L-NAME and L-NA were then removed by artificial cerebrospinal fluid washes.
      An additional CSD was induced with KCl as before. RESULTS: Control CSD in the L
      NAME group dilated pial arterioles; baseline diameter, 66 +/- 7 mm, with CSD =
      106 +/- 8 mm (59% increase). After topically applied L-NAME, CSD dilated pial
      arterioles less: baseline diameter, 61 +/- 7 mm, with CSD = 77 +/- 6 mm (26%
      increase), P < .05 compared with control CSD diameter. Topical L-NA had similar
      effects on CSD: control CSD dilated pial arterioles 51%; after topical L-NA, only
      14% (P < .05). After removal of L-NAME or L-NA, CSD-induced pial arteriolar
      dilation was similar to original control values. CONCLUSIONS: The reversible
      inhibition of CSD-induced pial arteriolar dilation by either L-NAME or L-NA
      suggests that NO contributes to arteriolar dilation observed with CSD.

PMID- 7526491
TI  - Rapid determination of platelet alloantigen genotypes by polymerase chain
      reaction using allele-specific primers.
AB  - BACKGROUND: The technique of allele-specific polymerase chain reaction (PCR)
      amplification has been adapted for DNA-based human platelet alloantigen typing.
      STUDY DESIGN AND METHODS: Sequence-specific primers were used to discriminate
      between the alleles encoding the six major human platelet alloantigens in a
      series of patients and normal blood donors. RESULTS: This technique allows the
      direct determination of platelet antigen genotypes from genomic DNA after PCR
      amplification and agarose gel electrophoresis. It offers significant advantages
      over previously described techniques for alloantigen identification, as the
      additional analytical steps of restriction enzyme digestion or dot blot
      hybridization are not required. The results obtained with this technique
      correlated precisely with those derived from serologic typing and allele-specific
      oligonucleotide hybridization. CONCLUSION: The use of allele-specific PCR for
      platelet alloantigen typing should facilitate the development of DNA-based typing
      in other regional blood centers and clinical laboratories.

PMID- 7526492
TI  - Duplication of exon 3 in the glycophorin C gene gives rise to the Lsa blood group
      antigen.
AB  - BACKGROUND: The Gerbich-related Lsa blood group antigen (Ge6) resides on the
      higher-molecular-weight forms of glycophorin C (GPC) and glycophorin D (GPD).
      Southern blot analysis has previously revealed an additional GPC exon 3 insert in
      the genomic DNA from an Ls(a+) individual. STUDY DESIGN AND METHODS: To confirm
      the duplication of exon 3 in the GPC mRNA, total RNA prepared from the Epstein
      Barr virus-transformed lymphocytes of an Ls(a+) individual was used in the
      synthesis of first-strand cDNA. The first-strand cDNA served as a template for
      the amplification of GPC-related DNA by polymerase chain reaction. After
      subcloning, the polymerase chain reaction cDNA was sequenced with a kit.
      Hemagglutination inhibition of anti-Lsa sera with synthetic peptides was
      performed to identify the location of Lsa on the GPC.Lsa protein. RESULTS:
      Sequencing the GPC.Lsa cDNA showed an insert of 84 nucleotides, which corresponds
      to the entire sequence of exon 3 in the GPC gene (GYPC). Since the exon 3
      duplicated exon 3 boundary of GYPC.Lsa encodes a novel amino acid sequence on
      GPC.Lsa and GPD.Lsa, synthetic peptides consisting of the amino acids flanking
      this junction were used to determine the amino acid sequence that is essential
      for expression of Lsa. The peptide DIVVIA/EPDPG was noninhibitory, while peptides
      with the sequence TPTIMDIVVIA/EPDPG or SPSVLDIVVIA/EPDPG inhibited anti-Lsa
      reactivity. CONCLUSION: Lsa is located within the sequence of amino acids encoded
      by the nucleotides at the exon 3-duplicated exon 3 boundary, and the conformation
      of this peptide sequence is important for recognition of Lsa by human anti-Lsa.

PMID- 7526493
TI  - CTLA4Ig prolongs allograft survival while suppressing cell-mediated immunity.
AB  - T cell activation is the result of antigen-specific interactions with the TCR/CD3
      complex and costimulation via other T cell surface receptors. Prevention of
      costimulation can result in clonal anergy. CTLA4Ig is a fusion protein that binds
      with high-affinity to the B7/BB1 ligand and blocks the interaction of this ligand
      with CD28 and CTLA4. We explored the immunosuppressive effects of CTLA4Ig in a
      murine nonvascularized heterotopic cardiac transplant model and in a model of
      cell mediated immunity. CTLA4Ig administered in vivo for two days at the time of
      transplantation resulted in significant prolongation of allograft survival (55 +/
      2.0 vs. 12.2 +/- 0.5 days for control, P < 0.03). Administration at later times
      or to previously primed animals produced no prolongation of graft survival.
      CTLA4Ig administered during in vivo immunization to the hapten TNP suppressed the
      contact sensitivity response and inhibited the subsequent in vitro generation of
      secondary TNP-specific CTL. CTLA4Ig administered in vivo had no effect on
      subsequent primary alloantigen-specific CTL or MLR responses--however, when added
      to culture the fusion protein inhibited the MLR response by 80%, but not the
      alloantigen-specific CTL response. CTLA4Ig inhibited CD4+ and CD8+ proliferative
      and cytokine responses to alloantigen. Flow cytometry showed no changes in
      distribution of subpopulations of T cells. These results confirm the
      immunosuppressive activity of CTLA4Ig in vivo in an allograft model and show that
      both CD4+ and CD8+ T cells are suppressed by CTLA4Ig. The most efficacious time
      of administration is during priming of the immune response at the time of antigen
      presentation.

PMID- 7526496
TI  - A polymerase chain reaction-based enzyme-linked immunosorbent assay for relative
      quantitation of T cell receptor beta-gene expression. Its application to the
      analysis of T cell receptor repertoire usage in alloreactive responses.

PMID- 7526495
TI  - Disruption of T cell development and repertoire selection by calcineurin
      inhibition in vivo.
AB  - The microbial products FK506 and CsA are potent immunosuppressive agents that
      prevent early transcriptional events in TcR-mediated activation. Their mode of
      action is dependent upon the inhibition of calcineurin, a serine/threonine
      phosphatase positioned within the calcium-dependent signaling pathway. TcR
      mediated activation of thymocytes constitutes an important prerequisite for their
      development and selection to mature T cells. Disruption of the cross-talk between
      thymic APC and thymocytes results in the loss of normal T cell ontogeny. To study
      the role of calcineurin in T cell maturation and repertoire selection in vivo,
      mice were treated with either FK506 or CsA. Administration of either drug
      inhibited the progression of CD4+CD8+ positive thymocytes to mature single
      positive T cells. Furthermore, both drugs disrupted the process of negative
      thymic selection, causing an increased frequency of self-reactive cells among the
      few positively selected T cells. These effects correlated directly with the
      degree of inhibition of in vivo calcineurin enzyme activity. Blocking calcineurin
      activity appears to disrupt positive thymic selection and to prevent the deletion
      of self-reactive thymocytes.

PMID- 7526497
TI  - Working round the clock with mouse 25.

PMID- 7526498
TI  - Superfluous neurotransmitters?
AB  - In recent years, studies have suggested that the complexity of eukaryotic gene
      regulation, with its recurring and interacting motifs of cis and trans-acting
      regulatory elements, might result in superfluous gene expression. This conclusion
      is supported by a variety of experimental results that suggest that non-adaptive
      gene expression might be common. However, with few exceptions, the practical
      ramifications of unnecessary gene expression for cell biologists have not been
      addressed directly; this is particularly true for peptidergic neurophysiology, a
      field that might be plagued more than most with the consequences of this
      phenomenon. In this article, Chauncey W. Bowers discusses the superfluous
      expression of neuropeptides in the nervous system in the context of gene
      regulation extrapolated from studies in Drosophila.

PMID- 7526494
TI  - The pharmacokinetic benefits of newly developed liposome-incorporated FK506.

PMID- 7526499
TI  - Trypanosoma brucei and the nervous system.
AB  - African sleeping sickness, characterized by a peculiar pain syndrome and
      prominent neuropsychiatric symptoms, is caused by the parasite Trypanosoma brucei
      (T.b.). In experimental T.b. infections, a molecule released from the
      trypanosomes has been isolated that binds to the CD8 molecule of T cells, whereby
      T cells are activated to secrete interferon gamma. This cytokine binds to the
      parasites and triggers them to proliferate, establishing a peculiar bidirectional
      activating signal system. The hypothesis is presented that the molecules involved
      in these bidirectional signals might also interact with neurons, thus causing
      brain dysfunctions. Studies on the molecular interactions between parasites and
      the nervous system in sleeping sickness might reveal basic mechanisms underlying
      other neuropsychiatric diseases.

PMID- 7526500
TI  - Neuroscience in Europe: the European Neuroscience Association.
AB  - The number of neuroscientists in Europe is large enough to match that of the
      neuroscientific community in North America. However, the degree of cohesiveness
      in the former is hampered by, among other things, the lack of a common language,
      the existence of geopolitical boundaries, and the dearth of pan-European funding
      initiatives. In this article, Wolf Singer, President of the European Neuroscience
      Association (ENA), discusses these issues and describes how the ENA is changing
      its organization, in particular the way in which its annual meeting is to be
      organized, in an effort to counteract the current deficiencies in European
      neuroscience.

PMID- 7526502
TI  - Discrepancies between identical amino acid sequences of cloned opioid-receptor
      subtypes and their binding data.

PMID- 7526501
TI  - Technology transfer in Europe: a case study of invertebrate neuroscience
      research.
AB  - Originally identified and defined as a concept in industrial and business
      communities, technology transfer is now being recognized as an important factor
      within the scientific research community. A recent study undertaken within the
      field of UK invertebrate neuroscience research generates several interesting
      conclusions. In this article, Huw A. Edwards and Elizabeth R.J. Bell discuss the
      study and its conclusions of a need for increased post-doctoral research
      mobility, the formation of consortia of research laboratories to apply for
      funding on an international scale, and the increased interest of the
      pharmaceutical industry in molecular and cellular techniques developed from
      fundamental invertebrate research.

PMID- 7526503
TI  - Amyloid precursor protein as a glial-derived growth factor.

PMID- 7526504
TI  - VIP and messenger plasticity.

PMID- 7526505
TI  - Osmoreception in magnocellular neurosecretory cells: from single channels to
      secretion.
AB  - Recognizing that osmotic pressure is a principal factor controlling antidiuresis,
      Verney introduced the term 'osmoreceptor' to designate the mysterious cerebral
      structures that regulate vasopressin release from the posterior pituitary. While
      hormone secretion from the neurohypophysis is influenced by synaptic inputs from
      other osmoresponsive neurons, magnocellular neurosecretory cells currently
      provide our most comprehensive model of signal detection in an osmoreceptor.

PMID- 7526506
TI  - Neurotransmission: harnessing fusion machinery at the synapse.
AB  - Neurotransmission requires the docking of synaptic vesicles to the presynaptic
      plasma membrane, and their signal-dependent fusion. These processes use a general
      'machinery' operating at several intracellular vesicular transport steps and, in
      addition, use a set of unique components that characterizes this specific form of
      regulated secretion. This review summarizes recent progress that has
      significantly increased our understanding of how intracellular transport vesicles
      dock and fuse with their target membrane, both in the synapse and elsewhere.

PMID- 7526507
TI  - Phosphorylation of dynamin I and synaptic-vesicle recycling.
AB  - In nerve terminals, neurotransmitters are packaged in synaptic vesicles, and
      released by exocytosis. Empty synaptic vesicles are rapidly recycled for reuse by
      endocytosis. Much progress has been made in identifying the proteins involved in
      synaptic-vesicle trafficking, but the mechanism and regulation of endocytosis
      have largely remained an enigma. One approach to defining regulatory proteins
      that might be involved is to study stimulus-dependent phosphorylation events in
      nerve terminals. This has led to the identification of dephosphin, which is
      quantitatively dephosphorylated by nerve-terminal depolarization. Sequencing
      reveals that dephosphin is identical with dynamin I, a GTP-binding protein that
      functions in endocytosis. Phosphorylation and dephosphorylation of nerve-terminal
      dynamin I/dephosphin regulates its intrinsic GTPase activity in parallel with the
      regulation of synaptic-vesicle recycling. Therefore, phosphorylation and
      dephosphorylation of dynamin I might provide a Ca(2+)-dependent switch for
      endocytosis in the synaptic-vesicle pathway.

PMID- 7526508
TI  - Dose intensification of chemotherapy in advanced breast cancer: a feasibility
      phase II study.
AB  - AIMS AND BACKGROUND: Dose intensification of chemotherapy is associated with
      increased response rates in advanced breast cancer. Achievement of dose
      incrementation is usually limited by drug-dependent bone marrow toxicity. The
      recent availability of recombinant human colony-stimulating factors (CSFs) have
      made it possible to evaluate their potential in ameliorating chemotherapy-induced
      myelosuppression. The aim of this study was to evaluate tolerability and
      effectiveness of an intensified mitoxantrone, methotrexate and mitomycin-C (3M)
      regimen, given with G-CSF support in patients with advanced breast cancer (ABC).
      STUDY DESIGN: Twenty-eight eligible patients with advanced breast cancer were
      treated with mitomycin -C (7 mg/sqm i.v. every 4 weeks), methotrexate (35 mg/sqm
      i.v.) and mitoxantrone (7 mg/sqm i.v. every 2 weeks) for 6 cycles. Recombinant
      human granulocyte colony-stimulating factor (r-HuG-CSF, Filgrastim) (5
      micrograms/kg/day) was given subcutaneously from day 2 to day 12 after each
      chemotherapy administration to prevent leukopenia. RESULTS: Of the 27 evaluable
      patients, 4 had complete response and 14 achieved partial response; the overall
      response rate was 63% (95% CI; 46.8%-82.2%). The median duration of response was
      8 months (range, 4-13+). Chemotherapy-related toxicity was mild: only 3 out of
      163 courses had to be postponed due to myelotoxicity. CONCLUSIONS: The 3M regimen
      given at 2- week intervals is a feasible, active and well toleratel treatment in
      patients not previously treated for metastatic breast cancer.

PMID- 7526509
TI  - R75251 in prostate cancer patients in progression after first-line hormonal
      treatment.
AB  - INTRODUCTION: The therapeutic potential of R75251, a ketoconazole derivative
      which has shown marked antitumor activity in animals and in men, was investigated
      in 16 patients with advanced prostatic cancer progressing after one or more lines
      of hormone therapy. PATIENTS AND METHODS: Patients were given the drug at 150
      mg/b.i.d. for one month. After the first month of treatment, the dose was
      increased to 300 mg/b.i.d. In all patients, treatment was continued until disease
      progression or the development of sever toxicity. Clinical and biochemical
      assessments were performed on days 0, 14 and 28 and then repeated on a monthly
      basis. RESULTS: Of the 13 evaluable patients, 12 showed stable disease by
      strictly employing US-NPCP criteria. However, in 3 patients a clear effect was
      observed on the volume of their measurable lesions. In addition, 2 of them showed
      a more than 50% decrease of prostate-specific antigens (PSA). Overall, 50% of
      patients showed some decrease in PSA baseline levels. Overall tolerance to
      treatment was good. CONCLUSIONS: Our results, although achieved in a small number
      of patients, suggest that R75251 has a moderate but definite activity in patients
      with hormone-refractory prostate cancer and that the value of this drug as second
      line treatment in these patients should be further investigated.

PMID- 7526510
TI  - [Effect of mineral substances on the biological value of eggs].
AB  - The experiments on pure-strain laying hens of meat direction showed that the
      mineral supplement consisting of sodium metasilicate, sodium sulfate, sodium
      bicarbonate and sodium selenite added to the standard feed of PK-1-26 composition
      improved the biological value of incubation eggs as a results of the increased
      quantity of glycogen, RNA, total lipids and carotenoids. This promotes and
      increase in hatchability of chicken by 0.45%.

PMID- 7526511
TI  - Prenatal screening for neural tube defects, quality specification of maternal
      serum alphafetoprotein analysis.
AB  - The bimodal approach for quality specification in prenatal screening for neural
      tube defects has been used. The method for assessing specifications has been the
      expenses for the society. It has been shown that the cut-off values and
      analytical bias are of importance. It is recommended to use a reference serum for
      local calibration to keep the level within defined limits when changing to a new
      batch of reagents.

PMID- 7526512
TI  - Quality specifications for S-AFP and S-HCG-beta determinations for screening of
      fetal abnormalities.
AB  - High levels of maternal serum alpha-1-fetoprotein (S-AFP) are associated with
      fetal structural abnormalities like neutral tube defects and congenital
      nephrosis. It has a very high detection rate when used for screening of these
      diseases. On the other hand, the low levels of maternal S-AFP act as a marker of
      many fetal chromosomal aberrations. The detection rate of S-AFP alone for the
      screening of Down's syndrome is low. Wald et al. have shown that the addition of
      the determination of maternal serum chorionic gonadotrophin (S-HCG-beta) to S-AFP
      analysis, and using a computer program for risk estimation increases the
      detection rate for Down's syndrome to about 57% with a false positive rate of 5%.
      In this study we present the results of our screening program for structural
      fetal defects and chromosomal aberrations in Eastern Finland, and describe the
      standardization and quality control of maternal serum AFP and HCG-beta analysis.

PMID- 7526513
TI  - Follow-up after radical prostatectomy or radiation therapy for prostate cancer.
AB  - The use of the serum marker prostate-specific antigen (PSA) has altered
      drastically the follow-up after prostate cancer. PSA is far superior to any other
      method of detecting recurrences after either radiation therapy or radical
      prostatectomy. Once the PSA reaches a nadir level after radiation therapy or
      becomes undetectable after radical prostatectomy, it should remain at that level.
      PSA provides a lead time of approximately 3 to 7 years prior to identification of
      recurrence or metastases by other traditional methods. The yield of diagnostic
      studies to identify the site of recurrence in patients with very low levels of
      PSA after radical prostatectomy is quite low. A substantial dilemma remains about
      optimal therapy once a rising PSA is identified.

PMID- 7526514
TI  - Patient evaluation if prostate-specific antigen becomes elevated following
      radical prostatectomy or radiation therapy.
AB  - Prostate-specific antigen (PSA) is the most sensitive and clinically useful
      method for monitoring patients following definitive therapy for prostate cancer.
      A "detectable" value following radical prostatectomy and an increasing level
      following radiation therapy are both indicative of recurrent/residual disease.
      The persistent cancer may be local or distant; the rate of increase of serum PSA
      can be useful in distinguishing between local and metastatic disease. A computed
      tomography or magnetic residence imaging scan may be useful for evaluating
      abdominal and pelvic lymph nodes, and the radionuclide bone scan is an effective
      tool for assessing the skeleton when the serum PSA concentration becomes elevated
      following treatment.

PMID- 7526515
TI  - Radiation therapy for local recurrence of prostate cancer after radical
      prostatectomy.
AB  - A definitive conclusion about the value of ART is not possible from the data
      available: Both the methods of radiation therapy and the techniques in the
      diagnosis of locally persistent disease have evolved over the years. Currently,
      the data lead to the conclusion that ART decreases local recurrence but does not
      improve overall survival. Yet the PSA data strongly suggest that only locally
      persistent disease is a common event after radical prostatectomy (particularly in
      margin-positive disease only) and that current ART techniques are inadequate in
      many but not all of these patients. Certainly some men seem to have their local
      disease eliminated by ART to remain NED, but it is unclear exactly how to select
      them. Many experts also believe that keeping the PSA as low as possible for as
      long as possible, with sequential applications of ART and then androgen ablation
      as necessary, is a good emotional if not medical strategy. For example, all
      patients now wish to know their PSA level and worry about it. Also, potency can
      be maintained or regained after ART but becomes improbable after androgen
      ablation because of loss of libido. Clearly, a study randomizing high-risk
      postoperative patients into observation versus ART is needed and indeed such a
      study is under way in the Southwestern and Eastern Cooperative oncology groups,
      but to date accrual is inadequate (Ian Thompson, Jr, MD, personal communication,
      May 1994). This study must be supported. When participation in the randomized
      study is not possible, we believe four tentative recommendations about the
      application of ART can be made based on the available data (Fig. 1): (1) For high
      risk patients (e.g., high Gleason score and/or high pathologic stage) with
      initially undetectable PSA levels, we recommend instituting ART before any rise
      in postoperative PSA levels because low-volume disease may best respond to this
      therapy. (2) For patients with rapidly rising or initially detectable
      postoperative PSA levels (especially if NBA is negative), we believe that the
      disease has most likely already spread to distant sites and would initiate
      therapy aimed at systemic disease. (3) For those patients with rapidly rising
      postoperative PSA but with positive NBA, we recommend local irradiation. (4) if
      the postoperative PSAlevels rise gradually, we would initiate ART regardless of
      the needle biopsy result because of the possibility of NBA sampling error and the
      fact that the gradual increase in PSA suggests that the disease is still
      local.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7526516
TI  - Role of surgery in managing local recurrence following external-beam radiation
      therapy.
AB  - Salvage surgery for radiation failure in prostate cancer has improved over the
      last 10 to 15 years owing to earlier detection of failure and better selection of
      patients. Regardless of the percentage of complications associated with this
      procedure, it presents the only viable alternative for potential cure of patients
      failing radiation therapy.

PMID- 7526517
TI  - Management of patients with positive surgical margins following radical
      prostatectomy.
AB  - The increase in diagnosis of patients with prostate cancer is related to a
      variety of factors, most notably the availability of prostate-specific antigen
      (PSA). The article explores the various stages of prostate cancer and a variety
      of techniques for clinically staging the disease including digital rectal
      examination, ultrasonography, computed tomography, and magnetic resonance imaging
      in relation to positive surgical margins.

PMID- 7526518
TI  - Evaluation and results of treatments for prostatism.
AB  - Men with symptoms of prostatism form a heterogenous group. The best treatment of
      proven obstruction or retention in fit men remains transurethral prostatectomy
      (TURP). Men presenting with symptoms of prostatism may have bladder outflow
      obstruction, detrusor instability or weak bladder contraction leading to low
      pressure/low flow voiding so it is perhaps not surprising that only 75% of men
      selected for TURP purely on the basis of symptoms have a good outcome. Pressure
      flow studies are the only precise method of diagnosing outflow obstruction. The
      problem of accurately diagnosing obstruction before treatment is started applies
      particularly to trials of new treatments such as lasers, high energy focused
      ultrasound and drugs. Laser treatment is producing short term results that are
      slightly inferior to TURP but may have less morbidity. The role of conservative
      treatment is important in selected men. Men who have severe intercurrent illness
      may be treated by means of intra-prostatic stents. In order to accurately assess
      a new treatment it is necessary to determine the short-term mortality, the
      morbidity, complication rate and outcome as well as the cost-effectiveness, long
      term outcome and patient preference. These conditions have not yet been met for
      any of the new treatments for prostatism.

PMID- 7526519
TI  - Culture and characterisation of human urothelium in vivo and in vitro.
AB  - The aim of this study was to culture human urothelium and generate enough cells
      for subsequent reconstructive surgery. Using a modification of the Rheinwald
      Green method for the routine culture of keratinocytes from patients with burns,
      we successfully cultured 91% of 57 biopsies from the renal pelvis, ureter,
      bladder and urethra of paediatric patients. The cells could be split one to three
      up to 9 times at 7-10 day intervals, giving a surface area of 1000 cm2 after a 2
      month culture period. Primary cultures could not be initiated in defined medium
      MCDB153, although cells initiated using the Rheinwald-Green method could
      subsequently be propagated in this medium. Cytokeratin patterns in vitro were
      similar to those in vivo in the expression of keratins 7, 18 and 19
      (characteristic of simple epithelia) and keratin 13 (characteristic of non
      cornified stratified epithelia). Cultured urothelium also expressed keratin 14
      (characteristic of cornified stratified epithelium) in about 25% of cells and
      keratin 16 (characteristic of fast-growing cells). These findings indicate that
      urothelial cells can be propagated in vitro for autologous grafting, and the next
      step is to identify substrates suitable for urothelial cell growth and
      differentiation and surgical manipulation.

PMID- 7526520
TI  - [Drug treatment of tumor pain].

PMID- 7526521
TI  - Benign prostatic hyperplasia: effects on quality of life and impact on treatment
      decisions.

PMID- 7526522
TI  - Racial differences in adenocarcinoma of the prostate in North American men.
AB  - Black men represent a particularly high risk group for the development of
      prostate cancer. Current recommendations are that all men over age 50 be screened
      for prostate cancer annually with a digital rectal examination (DRE) and PSA.
      Moreover, it has been recommended that men in high risk groups, including blacks
      and men with a family history of prostate cancer, be screened at an earlier age.
      At the present time, no adequately performed prospective study has demonstrated a
      reduction in mortality rate attributable to annual prostate cancer screening.
      Preliminary reports have suggested that the proportion of men with organ confined
      tumors increases with PSA based screening, and that a reduction in prostate
      cancer mortality via screening is feasible. In light of these preliminary
      studies, increased efforts toward patient awareness and PSA screening are
      certainly warranted in the black community. Hopefully the result of such programs
      would be to increase the percentage of black men diagnosed with organ confined
      prostate cancer. However, the etiology of these striking racial differences
      remains to be defined. To date no consistent data have been presented which can
      explain these observations. It is likely that multiple factors will be involved
      including socioeconomic, environmental, dietary, and genetic. Lastly, little is
      known of the molecular genetic factors, tumor suppressor genes and/or oncogenes,
      that play a role in prostate cancer in black men. Increased research efforts are
      needed in order to understand this problem at the molecular level.

PMID- 7526523
TI  - Concordance rates for benign prostatic disease among twins suggest hereditary
      influence.
AB  - OBJECTIVES: The etiology of benign prostatic hyperplasia (BPH) is unknown.
      Evidence for a hereditary trait would provide new avenues for investigation.
      METHODS: We compared the concordance for benign prostate disease in monozygotic
      (MZ) and dizygotic (DZ) twins who served in the United States military in World
      War II and have been followed by the Medical Follow-up Agency, Institute of
      Medicine of the National Academy of Sciences. Questionnaires completed in 1985 by
      10,000 twins were reviewed for evidence of prostatic disease. Key words
      indicating benign prostatic disease (prostate, prostatectomy, BPH, TURP, and
      prostatism) were identified in 533 (5.3%) of the questionnaires. RESULTS: The
      average age was 64 +/- 3 years (range 56 to 68 in 1985). After eliminating men
      with known prostate cancer, there were 256 twin pairs that were informative for
      benign prostatic disease: both twins were concordant in 25 instances and
      discordant in 231, with only one twin mentioning benign prostatic disease. The
      pairwise concordance for MZ twins was 14.7% (19 of 129) and for DZ pairs it was
      4.5% (5 of 112). The relative risk for benign prostatic disease for MZ twins was
      thus 3.3 (p = 0.008). The probandwise concordance rates, which express the
      probability of BPH in a cotwin of an affected twin, were 25.7% for MZ twins and
      only 8.5% for DZ twins. A covariance analysis estimated that 49% of the observed
      variance between twins could be attributed to genetic effects. CONCLUSIONS: These
      data provide preliminary evidence for the heritability of benign prostatic
      disease.

PMID- 7526524
TI  - Localization of nitric oxide synthase activity in the human lower urinary tract
      and its correlation with neuroeffector responses.
AB  - OBJECTIVES: The present study was designed to correlate the localization of
      nitric oxide synthase (NOS) activity to nerve-induced smooth muscle responses in
      the human lower urinary tract. METHODS: Nerve-induced smooth muscle activity was
      studied in the human lower urogenital tract. NOS activity was studied by
      measurement of citrulline formation and guanylate cyclase activity. RESULTS:
      Nerve-induced contractions in the human detrusor muscle, bladder neck, and
      prostatic urethra were not significantly enhanced by the NOS inhibitor N omega
      nitro-L-arginine methyl ester (L-NAME). In the prostatic urethra, relaxations to
      transmural nerve stimulation were obtained after increase in tension. The
      relaxations were abolished by L-NAME and restored by L-arginine. Nerve-induced
      relaxations were occasionally obtained in the bladder neck, whereas nerve-induced
      relaxations were never obtained in the detrusor muscle. Citrulline formation was
      highest in the prostatic urethra, it was intermediate in the bladder neck, and it
      was less pronounced in the detrusor muscle. Guanylate cyclase activity was also
      highest in the prostatic urethra, whereas there was no significant difference in
      guanylate cyclase activity in the bladder neck and detrusor muscle. CONCLUSIONS:
      The nerve-induced smooth muscle responses and the localization of NOS activity
      were in good agreement. Thus, in areas where marked relaxations to nerve
      stimulation were obtained, there was also a high NOS activity. The data suggest
      that nitric oxide is a mediator for the neurogenic dilation of the bladder neck
      and urethra during the micturition reflex.

PMID- 7526525
TI  - Preliminary study of the frequency of benign prostatic hyperplasia and prostatic
      cancer in China.
AB  - OBJECTIVES: This study determined the frequency of benign prostatic hyperplasia
      (BPH) and cancer of the prostate (CaP) in China. METHODS: Prostate specimens from
      321 unselected autopsies were collected from 1989 to 1992. Slices were cut
      vertically every 0.5 cm from apex to base. Five to 12 slices were obtained from
      each prostate. Specimens were stained with hematoxylin-eosin and Masson
      trichrome. Sixty surgical specimens obtained from cystoprostatectomies with
      intact prostate were included to determine the frequency of latent CaP. RESULTS:
      The frequency of BPH, by age, was as follows: 41 to 50 years, 13.2%; 51 to 60
      years, 20%; 61 to 70 years, 50%; 71 to 80 years, 57.1%; 81 to 90 years, 83.3%.
      The frequency of latent CaP, by age, was as follows: 41 to 50 years, 2.2%; 51 to
      60 years, 9.3%; 61 to 70 years, 5.9%; 70 years or older, 25%. Incidental CaP was
      found in 4.9% (33 of 676) of BPH surgical specimens. The incidence of and
      mortality from CaP in Beijing were 2.41 per 100,000 men and 1.19 per 100,000 men,
      respectively, between 1985 and 1987. CONCLUSIONS: BPH was rare in China in the
      early years of this century, but it has become a common disease in recent
      decades. The histologic frequency of BPH in China was similar to that in Western
      countries, but the histologic frequency of latent CaP was less than half that in
      Western countries. The incidence of and mortality from CaP in China are about 20
      times less than those in Western countries. Histologic CaP in a Chinese man is
      not as likely to evolve into clinical CaP as in a Western man.

PMID- 7526526
TI  - Transurethral resection of the prostate among Medicare beneficiaries in the
      United States: time trends and outcomes. Prostate Patient Outcomes Research Team
      (PORT).
AB  - OBJECTIVES: The purpose of this study was to examine the epidemiology of
      transurethral resection of the prostate (TURP) and associated risks among
      Medicare beneficiaries during the period of 1984 to 1990. METHODS: Medicare
      hospital claims for a 20% national sample of Medicare beneficiaries were used to
      identify TURPs performed during the study period. All reported rates were
      adjusted to the composition of the 1990 Medicare population. Risks of mortality
      and reoperation were evaluated using life-table methods. RESULTS: The age
      adjusted rate of TURP reached a peak in 1987 and declined thereafter. Similar
      trends were observed for all age groups. In 1990, the rates of TURP (including
      all indications) were approximately 25, 19, and 13 per 1000 for men over the age
      of 75, 70 to 74, and 65 to 69, respectively. The 30-day mortality following TURP
      for the treatment of benign prostatic hyperplasia (BPH) decreased from 1.20% in
      1984 to 0.77% in 1990 (linear trend, p = 0.0001). The cumulative incidence of a
      second TURP among men with BPH has likewise decreased steadily over time; in this
      study, the average was 7.2% over 7 years (5.5% when the indication for the second
      TURP was restricted to BPH only). CONCLUSIONS: The rate of TURP has been
      declining since 1987, conceivably due to increasing availability of alternative
      treatments or changes in treatment preferences of patients and physicians. Over
      the same period, the outcomes following TURPs have improved, perhaps due to
      improved surgical care and changes in patient selection.

PMID- 7526527
TI  - Relationship of tumor DNA-ploidy to serum prostate-specific antigen doubling time
      after radiotherapy for prostate cancer.
AB  - OBJECTIVES: DNA-ploidy is a strong prognostic factor for prostate cancer patients
      treated with definitive external beam radiotherapy. Using DNA/nuclear protein
      flow cytometry, three prognostic groups based on DNA-ploidy were identified: from
      good to poor, these are diploid, near-diploid, and nondiploid tumors. Since
      recent evidence indicates that the rate at which prostate-specific antigen (PSA)
      increases in the presence of biochemical failure is predictive of the time to
      clinical relapse, we examined the relationship between DNA-ploidy and PSA
      doubling time (PSA-DT). METHODS: Formalin-fixed paraffin-embedded tissues from 76
      patients treated at M.D. Anderson Cancer Center with definitive radiotherapy
      alone were analyzed for ploidy using DNA/nuclear protein flow cytometry. Of
      these, 24 of the 27 patients with a rising PSA profile had three or more post
      treatment PSA values from which the PSA-DTs were calculated. PSA-DTs were
      estimated using nonlinear regression techniques. RESULTS: The average PSA-DT for
      the 24 patients in this cohort was 11.3 +/- 10.5 months (+/- SD) with a median of
      8.4 months. Diploidy (n = 3) was associated with a PSA-DT of 27.0 +/- 22.8
      months, near-diploidy (n = 7) with a PSA-DT of 12.2 +/- 5.7 months, and non
      diploidy (n = 14) with a PSA-DT of 7.5 +/- 5.7 months (p = 0.004, Spearman rank
      test). Stage, grade, and pretreatment PSA, as well as the endpoints of local
      control, freedom from metastases, and freedom from any relapse, did not correlate
      significantly with PSA-DT values. However, when patients were subdivided by PSA
      DT into those with values 10 months or less (n = 14) and those more than 10
      months (n = 10), there was a correlation with 3-year actuarial freedom from
      relapse: 28% and 74%, respectively (p < 0.01, log-rank). This subdivision of PSA
      DT also correlated with DNA-ploidy (p = 0.03, chi-square) and stage (p = 0.04).
      CONCLUSIONS: The results show that there is a significant correlation of DNA
      ploidy with PSA-DT. Diploidy was associated with the longest PSA-DTs, near
      diploidy with intermediate PSA-DTs, and nondiploidy with short PSA-DTs. Patients
      with short PSA-DTs also had significantly higher actuarial rates of disease
      relapse at 3 years. These data confirm that PSA-DT is a strong predictor of tumor
      behavior and that patients who have nondiploid tumors probably require more
      aggressive, combined modality, treatment.

PMID- 7526529
TI  - Cryosurgery for stage T3 prostate cancer.

PMID- 7526528
TI  - Adjuvant radiation, chemotherapy, and androgen deprivation therapy for pathologic
      stage D1 adenocarcinoma of the prostate.
AB  - OBJECTIVES: A retrospective analysis of the results of an aggressive multimodal
      approach combining radical prostatectomy with adjuvant radiation, chemotherapy,
      or androgen deprivation therapy for patients with pathologic Stage D1 prostate
      carcinoma was performed to assess the impact of these therapies on survival,
      recurrence, local control, and morbidity. METHODS: Case records of 76 patients
      with pathologic Stage D1 tumors were reviewed. All had radical retropubic
      prostatectomy and were recommended adjuvant therapy based on the pathologic
      extent of the primary tumor and the number of involved lymph nodes. RESULTS: With
      a median follow-up of 7 years, overall survival was estimated to be 88% and 66%
      at 5 and 10 years, respectively, and equaled age- and race-matched controls.
      Prostate cancer-specific survival at 5 and 10 years was 88% and 74%,
      respectively. The probability of developing a clinically detectable recurrence
      (excluding prostate-specific antigen [PSA]) was 29% and 62% at 5 and 10 years,
      respectively. When PSA was added to the detection data, the probability of
      developing a recurrence increased to 58% and 78% at 5 and 10 years, respectively.
      Recurrence and cause-specific survival correlated with Gleason sum. Univariate
      analysis of the adjuvant therapies demonstrated no effect on survival, but
      adjuvant radiation alone and in combination with androgen deprivation increased
      the time to recurrence. Local control was excellent, surgical morbidity was
      equivalent to that of all patients undergoing prostatectomy during the same time
      period, and the morbidity of adjuvant therapy was minimal. CONCLUSIONS: Survival
      equivalent to age- and race-matched controls, with excellent control of the
      extensive primary tumor, can be achieved in patients with Stage D1 prostate
      carcinoma by a combination of radical prostatectomy and radiation therapy without
      the need for routine androgen deprivation therapy.

PMID- 7526530
TI  - Serum PSA decline after Casodex withdrawal.

PMID- 7526531
TI  - Molecular typing of Pseudomonas pseudomallei from imported primates in Britain.

PMID- 7526535
TI  - Analysis of the determinants of the satellite RNA of cucumber mosaic cucumovirus
      for high accumulation in squash.
AB  - Ix-satRNA is a 334-nt cucumber mosaic cucomovirus satellite RNA (CMV-satRNA) with
      the unusual property of accumulating to high levels in host plants of the family
      Cucurbitaceae. To identify the determinants for this unusual phenotype,
      recombinant satRNAs were obtained, by in vitro manipulation of full-length cDNA
      clones between clone-derived Ix5-satRNA and two other CMV-satRNAs that do not
      accumulate efficiently in squash: D4-satRNA, which differs in 7 positions from
      Ix5-satRNA, and B21-satRNA, which differs in 45 positions. The analysis of the
      accumulation in squash of these hybrid satRNAs showed that determinants for high
      accumulation in squash occur in three molecular domains: nucleotides 1-46 (a C at
      position 20), 47-185 (a C at position 102), and 185-334 (not identified). None of
      these determinants seemed to be necessary or sufficient to confer a phenotype of
      high accumulation in squash. They resulted, or did not result, in such a
      phenotype according to the sequences that occur in other parts of the satRNA
      molecule. Not all of the identified determinants were equally affected by
      sequence context. These results may suggest that the phenotype in squash is
      determined by the conformation of the satRNA.

PMID- 7526532
TI  - Correlation between monoclonal antibody reactivity and expression of CD4 and CD8
      alpha genes in the horse.
AB  - Equine peripheral blood lymphocytes (PBL) were enriched by positive selection
      using panning with a mixture of monoclonal antibodies against putative equine CD4
      (Equine Leucocyte Antigen Workshop antibodies WS 1 and WS 72), or CD8 molecules
      (Workshop antibodies WS 12, WS 49, and WS 74). RNA was extracted from CD4
      enriched cells (99% purity), from CD8 enriched cells (69% purity), from
      peripheral blood lymphocytes, and from neonatal equine thymus. RNA extracted from
      equine granulocytes and from equine kidney served as negative control. The RNA
      was electrophoresed in agarose and transferred to nylon membranes. Northern blots
      were hybridized with human and mouse cDNA probes for CD4 and CD8 alpha. The human
      CD4 probe detected a 2.9 kb RNA transcript in equine PBL, CD4 enriched
      lymphocytes, and thymocytes. The human CD8 alpha probe detected a 2.0 kb
      transcript in RNA from equine CD8 alpha enriched lymphocytes and thymocytes, but
      not from PBL or CD4 enriched lymphocytes. Mouse cDNA probes for CD4 and CD8 did
      not react with equine RNA. Results of hybridizations using the human probes
      support the assignment of the CD4 and CD8 specificities to the antibodies listed
      above. The results also suggest that the equine CD4 and CD8 alpha genes are more
      closely related to the human than to the murine counterparts.

PMID- 7526533
TI  - Direct measurement of the influenza A virus M2 protein ion channel activity in
      mammalian cells.
AB  - The influenza A virus M2 integral membrane protein has an ion channel activity
      which is thought to play an essential role in the uncoating process of influenza
      virus in infected cells and, for some strains of influenza virus, in maintaining
      the hemagglutinin in its pH neutral form during transport through the trans Golgi
      network. To demonstrate directly that the M2 protein forms an ion channel in
      mammalian cells, the M2 protein was expressed in CV-1 cells by using an SV40-M2
      recombinant virus and the whole cell membrane currents were recorded. It was
      found that the whole cell current was activated by low pH and inhibited by the M2
      ion channel-specific blocker, amantadine hydrochloride. Expression of an altered
      M2 protein that contains a deletion of four residues in the transmembrane domain
      (M2-del28-31) and that when found in influenza virus confers amantadine
      resistance, resulted in a current that was activated by hyperpolarization of the
      membrane, was pH insensitive, and was resistant to block by amantadine. The data
      obtained in mammalian cells for the wild-type M2 and M2-del28-31 protein ion
      channel activities were very similar to those obtained when using the
      heterologous oocyte expression system.

PMID- 7526534
TI  - Antigenic specificity of porcine T cell response against foot-and-mouth disease
      virus structural proteins: identification of T helper epitopes in VP1.
AB  - The contribution of each of the viral capsid proteins of foot-and-mouth disease
      virus (FMDV) in the T cell response of vaccinated pigs has been studied. Viral
      polypeptides, VP1 to VP4, were expressed as fusion proteins in Escherichia coli,
      and were used to stimulate peripheral blood mononuclear cells of vaccinated
      animals. Significant, dose-dependent responses to whole virion were detected in
      the seven animals analyzed and, in five of them, responses to recombinant
      polypeptides VP1, VP2, and VP3 were noticed, VP4 was recognized only by one of
      the pigs. Among the responder animals, VP1 and VP3 induced the higher
      proliferative responses. The patterns of recognition of a nested set of VP3
      fragments expressed as fusions in E. coli were different among the animals
      studied and were consistent with the presence of different T cell epitopes on the
      protein. Likewise, three of the four VP1 fragments induced significant responses
      and were differentially recognized by each of the animals tested. Partially
      overlapping synthetic peptides spanning VP1 amino acids 41 to 209 were used to
      identify T cell epitopes in this protein. The significant responses obtained in
      three of seven additional FMDV vaccinated outbred pigs analyzed revealed the
      existence of at least 11 different T cell epitopes distributed throughout the
      sequence studied, which were distinctly recognized by each of the responder
      animals. A peptide corresponding to a relevant B cell antigenic site, around
      amino acids 140-160, was shown to stimulate lymphocytes from two of the responder
      animals. Thus, the results obtained indicate that different T cell epitopes of
      capsid proteins VP1 and VP3 are recognized by pig populations. The different
      patterns of recognition of recombinant polypeptides and synthetic peptides
      observed among outbred animals support an important contribution of genetic
      restriction, probably mediated by MHC genes, to the individual T cell response in
      swine.

PMID- 7526536
TI  - Human papillomavirus types 6 and 11 have antigenically distinct strongly
      immunogenic conformationally dependent neutralizing epitopes.
AB  - Antibodies reactive to HPV types 6 and 11 were tested in ELISA and HPV-11
      neutralization assays to determine whether these closely related types shared
      cross-reactive neutralizing epitopes. A series of HPV-11 neutralizing monoclonal
      antibodies (N-MAbs) that targeted conformational epitopes on infectious HPV-11
      and HPV-11 L1 virus-like particles (VLPs) were tested for type-specificity of
      reactivity using intact HPV-6 L1 VLPs. Polyclonal antisera generated against
      intact HPV-6 L1 VLPs were also tested for HPV-11 neutralizing capacity using the
      athymic mouse xenograft system. The results demonstrated that conformationally
      dependent neutralizing epitopes on HPV-11 were very type-specific. Three of the
      four HPV-11 N-MAbs were negative for binding to HPV-6 L1 VLP, and the fourth
      demonstrated binding to HPV-6 L1 VLPs that was several orders of magnitude weaker
      than its binding to HPV-11 L1 VLP. The polyclonal anti-HPV-6 L1 VLP antiserum was
      only partially protective against HPV-11 infectivity even at a low dilution of
      1:100. In contrast, polyclonal anti-HPV-11 L1 VLP antiserum was completely
      protective at dilutions greater than 1:10,000.

PMID- 7526537
TI  - Interferon induction by HIV glycoprotein 120: role of the V3 loop.
AB  - We have studied the mechanism of IFN induction by HIV-1 in peripheral blood
      mononuclear cells (PBMC), using recombinant viral membrane glycoproteins as
      potential inducers. Whereas 8 nM HIVIIIB-derived gp120 resulted in IFN levels
      between 80 and 2000 IU/ml with PBMC from different donors, gp120 from the MN
      strain was not an inducer. Preincubation of HIVIIIB-gp120 with a monoclonal
      antibody (mAB) to its CD4 binding domain or of PBMC with a mAB to the gp120
      binding domain of CD4 abolished IFN induction. Antibodies against the third
      extracellular domain of CD4 which did not block binding of gp120, however, were
      also inhibitory. Furthermore, several mABs to the third variable loop (V3) of
      HIVIIIB-gp120 also blocked IFN induction, suggesting an important role of V3 in
      this process. This was further supported by the inhibitory action of peptides
      homologous to complete or partial sequences of V3. We conclude that after binding
      of gp120 to its CD4 receptor the V3 loop can be positioned close to the membrane
      of the responder cells by bending of gp120-occupied CD4 at its hinge region
      between extracellular domains 2 and 3. As a result V3 is able to interact with a
      V3-specific "secondary receptor" on the membranes of these cells. We suggest that
      it is the latter interaction which triggers IFN induction.

PMID- 7526538
TI  - Complement control proteins, CD46, CD55, and CD59, as common surface constituents
      of human and simian immunodeficiency viruses and possible targets for vaccine
      protection.
AB  - Complement control proteins include a group of membrane-bound surface antigens
      that protect cells from complement lysis by preventing formation of the membrane
      attack complex (MAC) of complement. HIV-1 and SIV are known to possess cellular
      proteins, making it possible that some of them contribute to the ability of these
      viruses to evade complement lysis. Three complement control proteins, CD46
      (membrane cofactor protein), CD55 (decay accelerating protein), and CD59 (HRF20),
      were found by flow cytometry to be expressed on the surface of CD4+ cell lines
      commonly used for HIV-1 and SIV synthesis. Monoclonal antibodies to each of these
      proteins precipitated HIV-1 IIIB and SIV delta/B670 synthesized in CEM x 174
      cells and two primary HIV-1 isolates synthesized in peripheral blood mononuclear
      cells, indicating that CD46, CD55, and CD59 are physically associated with the
      virus membrane after the virus has been released from the surface of infected
      cells. Additional experiments showed that the precipitated material contained
      infectious virus, confirming that whole virus was precipitated. Evidence that
      CD46 and CD59 are immunogenic in macaques was found when anti-cell antibodies in
      plasmas from macaques immunized with human cell-grown SIV blocked anti-CD46 and
      anti-CD59 from binding to the surface of CEM x 174 cells. Anti-cell antibodies
      rendered HIV-1 susceptible to complement lysis as measured by the release of p24
      core protein, and consistently produced a complement-dependent reduction in HIV-1
      and SIV infectivity of 1-3 logs. These results demonstrate that CD46, CD55, and
      CD59 are common surface constituents of HIV-1 and SIV. The results also raise the
      possibility that the mechanism of SIV vaccine protection attributed to anti-cell
      antibodies could have involved complement-mediated virolysis.

PMID- 7526539
TI  - Detection of rice tungro bacilliform virus gene products in vivo.
AB  - To study the products of the open reading frames (ORFs) of rice tungro
      bacilliform virus in rice plants the sequences containing ORFs I (encoding a 24
      kDa protein, P24) and IV (P46) and the protease and polymerase (reverse
      transcriptase+RNaseH) domains of ORF III were cloned into a pGEX expression
      vector. The proteins, which were C-terminal fusions to glutathione S-transferase,
      were expressed in Escherichia coli and antisera were raised against them which,
      together with an antiserum against virus particles, was used to probe blots of
      proteins from infected and uninoculated plants and from virus preparations. The
      P24 antiserum detected virus-specific proteins of 74, 60, and 52 kDa, which are
      much bigger than expected. These proteins were found in virus preparations and
      immunogold labeling suggested that they might be internal in the particles. Virus
      specific proteins of 33, 37, 62, and > 150 kDa were revealed by antiserum to
      virus particles. The antiserum to the protease revealed proteins of 13.5, 37, and
      68 kDa both in extracts from infected plants and in purified virus preparations.
      This antiserum decorated intact virus particles as did the particle antiserum.
      The polymerase domain antiserum reacted with products of 56, 65, and 68 kDa in
      extracts from infected plants but not in virus particles. The antiserum to the
      ORF IV product did not detect any bands in either infected plant extracts or
      virus preparations. The significance of these products is discussed.

PMID- 7526540
TI  - Characterization of antigenic determinants in the core antigen of the hepatitis C
      virus.
AB  - Antibodies to the hepatitis C virus (HCV) core protein are present in the
      majority of patients with chronic HCV infection. To characterize the
      corresponding determinants, synthetic peptides and various deletion clones of the
      core gene expressed in Escherichia coli were used to test human anti-core
      positive sera or rabbit anti-peptide antibodies in enzyme-linked immunosorbent
      assays, immunoblots, and competition assays. Two distinct linear antigenic
      determinants which are located within aa 1 to 20 and between aa 30 and 47 were
      found. Further studies using reactive serum after preabsorption of antibodies
      with N- and C-terminal-deleted HCV core proteins or with peptides directed to the
      linear epitopes revealed an additional determinant that requires for presentation
      the participation of the N-terminal 69 amino acids. It is postulated that the HCV
      core protein forms a three-dimensional structure exposing two linear epitopes
      and, in addition, presents a conformational determinant within the N-terminal 69
      amino acids. The remaining core amino acid sequence spanning from position 69 to
      191 does not seem to expose further determinants to induce additional anti-core
      antibodies.

PMID- 7526542
TI  - Characterization of two density populations of feline calicivirus particles.
AB  - Feline calicivirus (FCV) F9 strain was propagated in Crandall-Reese feline kidney
      cells. Two density populations of viral particles were observed after equilibrium
      centrifugation in an isopyknic CsCl gradient. The buoyant density of the heavy
      particle (PH) is 1.33 g/ml. The light particle (PL), a previously undescribed
      form of feline calicivirus, has a buoyant density of 1.22 g/ml. The PH and PL
      presented a similar morphology by electron microscopy. Western blot showed that
      both PH and PL contained a major polypeptide of the typical FCV capsid protein
      with a molecular weight of 62,000. Infectivity assay and RNA isolation
      demonstrated that PH is the intact infectious virion while PL is FCV empty
      capsid.

PMID- 7526541
TI  - The basic domain of the lentiviral Tat protein is responsible for damages in
      mouse brain: involvement of cytokines.
AB  - The HIV and visna lentiviruses induce an inflammatory reaction in the central
      nervous system (CNS) of the infected hosts leading to dysmyelination,
      demyelination, and neuronal loss. The basic domain of the transactivating Tat
      protein has been involved in CNS damage. Infusion of basic containing domain Tat
      peptides in the lateral ventricle (systemic injection) or in the grey matter,
      i.e., hippocampus and thalamus (local injection), induced an inflammatory process
      characterized by the formation of an edema and invasion of macrophage accompanied
      by reactive astrogliosis. Control peptides originating from either lentiviral
      proteins or irrelevant protein as ovalbumin did not lead to any inflammatory
      reaction or cell death. The inflammation led to the loss of ependymal cells in
      the lateral ventricles and neurons in the grey matter. RNA extracted from the Tat
      injected hemisphere reacted with TNF-alpha, IL-1 alpha and beta, and IL-6 probes.
      The macrophage/microglia inducible nitric oxyde synthase was also expressed.
      Blockade of TNF-alpha by a pentoxifylline treatment led to the decrease of IL-1
      and iNOS expression accompanied by a reduction of the volume of the lesions
      indicating that the Tat-induced lesions might be mediated by TNF production.

PMID- 7526543
TI  - Dual specificity of a monoclonal anti-idiotypic antibody for HIV-1 neutralizing
      monoclonals 110.3 and 110.4 as well as the V3 loop of gp120.
AB  - Monoclonal antibodies (MAbs) 110.3 and 110.4 bind an epitope at the tip of the
      third hypervariable region (V3) of the envelope protein gp120 of human
      immunodeficiency virus type 1 (HIV-1). These MAbs inhibit HIV-induced syncytium
      formation and neutralize cell-free virus infection. Anti-idiotypic MAb alpha-id8,
      generated against 110.3, was found to mimic the V3 loop of gp120, as demonstrated
      by competition ELISA and by the generation of anti-anti-idiotypic sera which
      bound gp120 and a peptide representing the tip of the V3 loop. Interestingly,
      alpha-id8 itself also reacted specifically with both gp120 and the V3 loop
      peptide. Thus, alpha-id8 both mimics and binds directly to the V3 loop,
      suggesting that the V3 loop of gp120 may associate with itself.

PMID- 7526544
TI  - Mapping helper virus functions for cucumber mosaic virus satellite RNA with
      pseudorecombinants derived from cucumber mosaic and tomato aspermy viruses.
AB  - P-TAV is a strain of tomato aspermy virus (TAV) able to efficiently support the
      systemic accumulation of some (i.e., B2-satRNA) but not of other (i.e., Ix
      satRNA) strains of the satellite RNA (satRNA) of cucumber mosaic virus (CMV) in
      both tobacco and in tomato. As reported for V-TAV, the failure to support the
      systemic accumulation of Ix-satRNA seems to be due to an inefficient support of
      its systemic movement. Pseudorecombinants obtained by the exchange of RNAs 1 + 2
      between P-TAV and Trk7-CMV, an efficient helper for the systemic accumulation of
      Ix-satRNA, were assayed for their ability to support the accumulation of CMV
      satRNAs in tobacco plants and protoplasts. Pseudorecombinants having RNAs 1 + 2
      from CMV supported the systemic movement and accumulation of CMV-satRNA as
      efficiently as CMV, whereas pseudorecombinants having RNAs 1 + 2 from TAV
      supported the CMV-satRNA very poorly. Thus, the ability to support the systemic
      movement and accumulation of CMV-satRNA is determined primarily by RNAs 1 + 2 and
      not by RNA 3, which is presumed to encode movement functions in the cucumoviruses
      and only has a minor, modulating effect on the systemic accumulation of satRNA.
      This suggests that for systemic movement CMV-satRNA has to interact with (the
      gene products of) RNAs 1 and/or 2 or that these viral RNAs compete with the
      satRNA for interaction with the coat or other movement proteins.

PMID- 7526546
TI  - National Hospital Discharge Survey: annual summary, 1992.
AB  - This report presents statistics on the utilization of non-Federal short-stay
      hospitals based on data collected through the National Hospital Discharge Survey
      from a national sample of the hospital records of discharged inpatients.
      Estimates are provided by the demographic characteristics of patients discharged,
      geographic region of hospitals, conditions diagnosed, and surgical and
      nonsurgical procedures performed. Measurements of hospital use include frequency,
      rate and percent of discharges and days of care, and average length of stay.

PMID- 7526545
TI  - Detailed diagnoses and procedures, National Hospital Discharge Survey, 1992.
      Series 13: Data from the National Health Survey.
AB  - This report presents statistics on conditions diagnosed and surgical and
      nonsurgical procedures performed in non-Federal short-stay hospitals. The
      statistics are based on data collected through the National Hospital Discharge
      Survey from a national sample of the hospital records of discharged inpatients.
      Estimates of first-listed diagnoses, all-listed diagnoses, days of care for first
      listed diagnoses, and all-listed procedures are shown by sex and age of patient
      and geographic region of hospital.

PMID- 7526548
TI  - [The stomach cancer problem remains the leading one in current clinical
      oncology].

PMID- 7526547
TI  - [Cellular mechanisms of calcium regulation of cardiac rhythm in children with
      ectopic arrhythmias].
AB  - Regulation of intracellular calcium homeostasis by means of secondary mediators
      calmodulin and 4,5-inositol phosphates (products of phosphatidyl inositol
      hydrolysis) was studied in children with ectopic forms of arrhythmias.
      Alterations in the system calmodulin-Ca2+ and the activity of phosphoinosite
      metabolism correlated highly with clinical manifestations of the arrhythmias. The
      data obtained suggest that a number of molecular mechanisms and responsible for
      arrhythmias were realized in cell membranes and depended on a complex of
      intracellular messengers affected within various steps of the hormonal signal
      transmission.

PMID- 7526549
TI  - [Effect of fasting on anaphylaxis in sensitized rats].

PMID- 7526550
TI  - [Characteristics of anaphylaxis in fasting rats].
AB  - The effect of 4-day fasting was studied in male Wistar rats (200-150 g)
      sensitized by ovalbumin on anaphylaxis manifestations in vivo, antigen-dependent
      histamine secretion by mast cells in vitro, concentration of serum specific IgG
      antibodies. The fasting ended by a shocking allergen dose. It is shown that in
      the condition of food deprivation anaphylactic severity significantly lowered as
      well as antigen-dependent histamine secretion by mast cells. No changes were seen
      in the levels of specific antibodies in the serum.

PMID- 7526551
TI  - Are synthetic peptides sensitive enough for screening anti-hepatitis C virus at
      blood banks?

PMID- 7526552
TI  - Processing of hematopoietic stem cells: purging or selection?

PMID- 7526553
TI  - Immunity in hepatitis C virus infection.
AB  - Immunity after HCV infection is weak, even after reinfection with the identical
      strain of virus. Even chronically infected chimpanzees can be reinfected. Weak
      immunity may reflect the fact that HCV virions are coated with lipoproteins
      (VLDL), preventing antibody binding. This phenomenon presents a serious challenge
      for development of vaccines.

PMID- 7526554
TI  - The clinical role of hematopoietic growth factors in peripheral blood progenitor
      cell transplantation.

PMID- 7526555
TI  - Molecular genetic basis of Rh and LW blood groups.

PMID- 7526557
TI  - [Comparative evaluation of some morphologic methods for detecting Helicobacter
      pylori in gastric mucosa].
AB  - Gastroscopic examination was performed in 183 patients with upper
      gastrointestinal symptoms, with brush biopsy and taking of mucosa specimens for
      cytological and histopathological examination in order to detect the presence of
      Helicobacter pylori. Greater effectiveness of brush biopsy was demonstrated in
      comparison to histological examination of tissue fragments and significantly
      higher effectiveness of staining using the Giemsa-May-Grunwald method was shown
      in comparison to staining with hematoxylin and eosin.

PMID- 7526556
TI  - [Changes in the levels of tumor markers in those working with different
      chemically active substances].
AB  - Groups at risk for malignant neoplasia were identified among workmen
      occupationally exposed to different chemical substances, using immunoradiometric
      and enzyme immunoassays of tumor-associated antigens. Exposure to the above
      occupational hazard was found to affect the workmen and cause certain chronic
      illness accompanied by some increase in concentration of a number of tumoral
      markers. Increase in tumour antigens suggests indirectly that the chemical
      substances may have carcinogenic activity. We have every reason to recommend
      these tests as an additional method for identification of groups at high risk for
      subsequent development of tumours in the digestive system and reproductive organs
      of persons occupationally exposed to chemical substances.

PMID- 7526558
TI  - [Effect of rectal examination in patients with prostatic adenoma on concentration
      of prostatic specific antigen (PSA) in plasma].
AB  - The results are presented of a study in 88 patients with prostatic adenoma in
      whom plasma PSA concentration was determined before rectal examination and 1 and
      24 hours after it. The mean value of PSA concentration before the examination was
      about 6.9 ng/ml (maximal value 27.0 ng/ml, minimal value 0.3 ng/ml, SD 6.2).
      After the examination (after 1 and 24 hours) an increase of PSA concentration
      occurred and it was 7.7 ng/ml (maximal value 28.9 ng/ml, minimal value 0.5 ng/ml,
      SD 6.7) and 8.6 ng/ml (maximal value 28.0 ng/ml, minimal value 0.5 ng/ml, SD
      7.9), respectively. It was found that in the studied patients with prostatic
      adenoma an increase of plasma PSA concentration occurred after per rectum
      examination.

PMID- 7526559
TI  - [A case of Whipple disease].

PMID- 7526560
TI  - [Strongyloides stercoralis (Bavay, 1976) Stiles et Hassall, 1902 (Nematoda)-
      intestinal roundworm. II. Geographic distribution].
AB  - General data in the world of Strongyloides stercoralis infection in human hosts,
      were presented. In addition, particular distribution of parasite in Asia,
      Oceania, Australia and America were described.

PMID- 7526561
TI  - C-raf expression in early rat liver tumorigenesis after promotion with
      polychlorinated biphenyls or phenobarbital.
AB  - 1. The expression of c-raf protooncogene in early stages of chemically induced
      rat liver tumorigenesis was studied in weanling female and adult male Sprague
      Dawley rats. After initiation with diethylnitrosamine, promotion by
      polychlorinated biphenyls (PCBs) or phenobarbital (PB) was studied in the female.
      Male rats were promoted with PCBs only. 2. The incidence of enzyme-altered foci
      was evaluated histochemically by demonstrating a deficiency in adenosine-5'
      triphosphatase and the emergence of gamma-glutamyl-transpeptidase. C-raf
      expression was measured in liver tissue containing preneoplastic foci, and in
      small (< 3 mm in diameter) and large (> 3 mm in diameter) neoplastic nodules up
      to 36 weeks. 3. Foci numbers amounted to 60-70 per cm2 liver section with both
      histochemical markers and both promoters in female rats. In male rats foci
      numbers were about 20-40 per cm2 liver section with both markers and with PCBs as
      promoting agents. Foci area developed more rapidly in female rats. 4. Small and
      large nodules were found in females during the entire observation period with
      both promoting agents, PCBs being more effective than PB. C-raf expression in
      nodules was increased up to 10-fold in PCB-treated animals compared with
      untreated controls. No dependence on the size of the nodules was seen. In male
      rats nodule incidence was very low and c-raf induction was marginal. 5. In
      conclusion, c-raf proto-oncogene expression correlated with the incidence of foci
      and nodules, female rats being more sensitive than males.

PMID- 7526562
TI  - Treatment response with transurethral radiofrequency thermotherapy for
      symptomatic benign prostatic hyperplasia.
AB  - One hundred and two patients with benign prostatic hyperplasia were treated by
      transurethral radio-frequency thermotherapy (TURT) device (Thermex-II, Direx,
      Israel) with 47.5 degrees C in single session for 2 hours and 30 minutes from
      November 1992 to October 1993. Among them, 83 patients, who were followed up for
      more than 3 months were included in this study. Twenty-seven (32.5%) patients had
      a history of acute retention. Pretreated values of the mean Madsen-Iversen
      symptom score, maximum urine flow rate, postvoiding residual urine volume,
      prostate volume and prostate specific antigen (PSA) were 15.4, 6.5 ml/sec,
      61.3ml, 43.2ml and 0.77 ng/ml respectively. Madsen-Iversen symptom score, maximum
      urine flow rate were measured at 2 weeks, 1, 3 and 6 months after TURT. The
      residual urine volume, prostate volume and PSA level were measured at 3 and 6
      months after TURT. During the follow up, the symptom score started to decrease
      significantly at 1 month (9.9, p < 0.01) after TURT, and gradually decreased up
      to 6.9 at 3 months. The maximum flow rate showed initial significant improvement
      at 2 weeks (8.1 ml/sec., p < 0.01), but no significant interval change was
      observed thereafter. The residual volume decreased significantly at 3 months
      (41.3 ml, p < 0.01) and no decrement was noted until 6 months. Neither the
      prostate volume nor PSA value changed significantly at 3 or 6 months after TURT.
      The improvement, which was defined as a change of 50% or more in at least one of
      subjective or objective symptoms showed in 63.9% (53/83) at 3 months and 57.1%
      (32/56) at 6 months. Both subjective and objective improvements at 3 and 6 months
      after treatment showed in 24.1% and 19.6%, respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7526563
TI  - Clinical evaluation of a new polymerase chain reaction assay (Amplicor HCV) for
      detection of hepatitis C virus.
AB  - Direct detection of hepatitis C virus (HCV) by reverse transcription (RT) and
      polymerase chain reaction (PCR) has clinical impact on diagnosis and the
      assessment of anti-viral therapy. However, recent results of a quality control
      study on the detection of HCV-RNA by RT-PCR revealed inappropriate sensitivity
      and specificity in the majority of participating laboratories. In this study we
      evaluated the first standardized RT-PCR-assay (Amplicor HCV) for routine
      detection of hepatitis C virus in serum samples from patients with hepatitis C (n
      = 111), patients with resolved acute hepatitis C (n = 7) and controls (n = 101).
      The Amplicor HCV assay was convenient to handle, detected all genotypes of the
      hepatitis C virus commonly present in Europe (type 1, 2 and 3 according to
      Simmonds et al.) and had a lower detection limit of 10(2)-10(3) copies as
      assessed by quantifiable HCV-specific RNA templates. In the clinical evaluation
      the Amplicor HCV system reached a sensitivity of 100% and a specificity of 97%.

PMID- 7526564
TI  - Gastroenterologic manifestations of mastocytosis.
AB  - Mastocytosis as a rare disease is usually diagnosed by dermatologists because of
      urticaria pigmentosa as one of the leading signs. If the triad of urticaria
      pigmentosa, flush and diarrhea is present diagnosis is easily made. However,
      urticaria pigmentosa and flush may be less dominant or even absent and
      gastrointestinal signs may render diagnosis more difficult. Therefore, this
      review is thought to describe clinical manifestations of mastocytosis from the
      gastroenterologist's point of view. In addition, on the grounds of a recent
      classification of mastocytosis practical diagnostic procedures as well as
      therapeutic approaches are discussed.

PMID- 7526565
TI  - [Prenatal risk index for fetal Down's syndrome with serum markers. Comment on the
      contribution by R. Benz, U. Muller, M. Krahner-Pilat, S. Wagner-Geuder, R.
      Terinde: Serum screening for Down's syndrome in women less than 35 years of age
      with an age-independent index].
AB  - 5 years ago, maternal serum markers have been established for individual risk
      estimation of fetal Down syndrome. Recently Benz et al. presented an arbitrary
      age-independent risk index. Compared to the commonly applied statistical approach
      a 20% increase in detection rate was obtained by using the index (85% versus
      65%). We recalculated data from 19,333 prospectively investigated pregnancies
      without trisomy 21 and 57 pregnancies with fetal Down syndrome using the proposed
      risk index. At the corresponding false-positive rate (7.9%) the age-independent
      detection rate was only 56%. This result indicates that the sensitivity cannot be
      increased by the Ulm index, when compared to statistical methods of risk
      estimation.

PMID- 7526567
TI  - Salmonella typhi O-polysaccharide--tetanus toxoid conjugated vaccine.
AB  - A Salmonella typhi conjugated vaccine was prepared by covalently linking the
      antigenic O-polysaccharide, selectively activated by periodate oxidation, to
      tetanus toxoid via reductive amination. The immunogenicity of the conjugate (O
      TT) was examined by injecting Balb/c mice with 5 micrograms of the conjugate and
      Alhydrogel as adjuvant, boosting 14 and 28 days after the primary immunization,
      and quantification of the development of anti-polysaccharide and anti-tetanus
      toxoid antibodies by enzyme-linked immunosorbent assay. Mean anti-O-chain titres
      after the first and second boost were 129 and 502, respectively, while anti
      tetanus toxoid titres were 159 and 1000, respectively. Anti-O-polysaccharide
      antibodies exhibited complement-mediated bactericidal activity against S. typhi.
      Immunized mice were fully protected against challenge with 10 LD50 of S. typhi
      Ty2 (p < 0.001) and partially protected against challenge with 100 LD50 of S.
      typhi Ty2 (p < 0.04).

PMID- 7526568
TI  - Modulation of immune responses in Balb/c mice vaccinated with Brucella abortus Cu
      Zn superoxide dismutase synthetic peptide vaccine.
AB  - Three peptides, peptide 1 (GGDNYSDKPEPLGG), peptide 2 (LAEIKQRSLMVHGG) and
      peptide 3 (GGAPGEKDGKIVPAG), were synthesized based on the amino acid sequence of
      Brucella abortus Cu-Zn superoxide dismutase. These peptides were selected on the
      basis of their predicted hydrophilicity, flexibility and antigenicity profiles.
      The three peptides, singly or in combination, with or without the adjuvant
      monophosphoryl lipid A were administered to Balb/c mice as vaccines for
      brucellosis. The protective and immune responses induced by the peptide vaccines
      after challenge exposure to virulent B. abortus strain 2308 were compared to
      those obtained with salt-extractable proteins (BCSP) vaccine prepared from B.
      abortus strain 19, recombinant B. abortus Cu-Zn superoxide dismutase (rSOD)
      vaccine and non-vaccinated mice. Mice vaccinated with 30 micrograms of peptide 3
      plus 50 micrograms monophosphoryl lipid A afforded two logs of protection
      (reduction in log10 colony-forming units compared with control mice) and one log
      of protection when given without monophosphoryl lipid A, whereas 5 micrograms of
      the salt-extractable proteins afforded three logs of protection. The rSOD and
      peptides 1 and 2 given with or without monophosphoryl lipid A afforded no
      protection. Superoxide dismutase-specific IgG antibody was present in
      postchallenge sera only if BCSP was present in the vaccine. Peptide-specific IgG
      antibodies were present in postchallenge sera of mice, and antibody
      concentrations were generally enhanced when monophosphoryl lipid A was included
      in the vaccine. The overall results with the peptide vaccines suggest that
      peptide 3 probably contains a specific sequence preferentially recognized by the
      cellular immune system leading to modulation of immune response mechanisms
      responsible for decreasing splenic infection.

PMID- 7526566
TI  - Overcoming class II-linked non-responsiveness to hepatitis B vaccine.
AB  - This work shows that class II-linked humoral lack of response to an antigen can
      be overcome by joint immunization with the antigen and a T-helper cell
      determinant (TDh) well recognized by class II molecules of a non-responder
      individual. Thus, SJL/J mice (H-2s), which are non-responders to the S region of
      hepatitis B virus surface antigen (HBsAg), were rendered responders by joint
      immunization with a recombinant surface antigen, only composed of the S region,
      and a short synthetic TDh peptide well recognized by the H-2s restriction. By
      contrast, when this peptide is not recognized as TDh, as in B10M mice (H-2f
      restricted and also non-responders to the S region), no humoral response could be
      induced against the S region. These results have important implications for
      therapy and vaccination against hepatitis B virus as well as in enhancing the
      immunogenicity of other antigens.

PMID- 7526569
TI  - Epitope-specific antibody responses in market-stressed calves to bovine
      herpesvirus type 1.
AB  - Reciprocal competition ELISA (rcELISA) was conducted to map monoclonal antibodies
      (mAbs) reactive with gI, gIII and gIV glycoproteins of bovine herpesvirus type 1
      (BHV-1) into epitope groups. mAbs to glycoproteins gI and gIV were divided into
      six epitope groups each, while gIII mAbs had been previously divided into four
      areas. mAbs were chosen from each epitope group to compete in cELISA wih bovine
      sera collected during a typical regimen of vaccination and transportation from
      farm to auction to feedlot. The immunodominant epitopes were identified for each
      BHV-1 glycoprotein. With glycoprotein gI, three epitopes defined by mAbs 1F10, D9
      and 4807 were the most dominant; with glycoprotein gIII epitopes defined by mAbs
      G2 and 1507, and with glycoprotein gIV epitopes defined by mAbs 1102, 1106, 3C1,
      3402 and 3E7 showed the maximum responses. The overall cELISA responses to each
      glycoprotein among two vaccination groups were also compared and it was shown
      that cELISA responses were significantly higher for each glycoprotein in calves
      receiving two vaccinations, one on the farm of origin and one at auction, than in
      calves receiving only one vaccination at auction.

PMID- 7526570
TI  - Immunogenicity of an alum-adsorbed synthetic multiple-antigen peptide based on B-
      and T-cell epitopes of the Plasmodium falciparum CS protein: possible vaccine
      application.
AB  - Multiple-antigen peptides (MAPs), containing B- and T-cell epitopes of the
      Plasmodium falciparum circumsporozoite (CS) protein, have been designed to
      overcome the limitations of first-generation peptide vaccines caused by low
      epitope density, carrier toxicity and the lack of parasite-derived T-cell
      epitopes. The immunogenicity of a P. falciparum MAP construct (T1B4), containing
      four copies of the 5' repeat cell T epitope (T1) combined with the 3' repeat
      epitope (NANP)3, has been examined using different adjuvant formulations. Mice
      immunized intraperitoneally or subcutaneously with (T1B)4 in alum, a formulation
      suitable for human vaccines, developed high anti-peptide and anti-sporozoite
      antibody titres, comparable with those obtained with Freund's adjuvant. The
      MAP/alum formulation also elicited a strong anamnestic antibody response in
      sporozoite-primed mice, raising the possibility of using a MAP/alum vaccine to
      increase the low anti-sporozoite antibody levels of people living in malaria
      endemic areas.

PMID- 7526571
TI  - Analysis of epitopic residues introduced into the hybrid peptide vaccines
      prepared according to the cassette theory.
AB  - In our previous study, we prepared a synthetic peptide vaccine (46F/HA127
      133/54A) against influenza strain A/Aichi/2/68 (H3N2) virus by introducing
      haemagglutinin (HA) 127-133 to an I-Ab,b binding component that consisted of
      residues 43-46 and 54-58 of an I-Ab,d binding peptide, 46F50V54A. This hybrid
      peptide vaccine induced considerable immunological responses against A/Aichi/2/68
      as well as against the peptide vaccine in I-Ab mice. In the present study, we
      have attempted to increase the immunogenicity of the peptide vaccine by
      introducing HA peptides of various lengths into the I-Ab,d binding components
      consisting of residues 43-46 and 54-58 or 43-47 and 53-58 of 46F50V54A. We
      demonstrate here that, among the peptide vaccines prepared, 46F/HA127-133/54A (18
      mer) consisting of HA127-133 and the I-Ab,d binding component constructed from 43
      47 and 53-58 of 46F50V54A induces the most vigorous T-cell responses and
      neutralizing antibodies against A/Aichi/2/68 in both I-Ab and I-Ad mice.

PMID- 7526572
TI  - Construction of a synthetic immunogen: use of the natural immunomodulator
      polytuftsin in malaria vaccines against RESA antigen of Plasmodium falciparum.
AB  - Polytuftsin, a 35-40-unit repeat of the naturally occurring tetrapeptide tuftsin
      (TKPR), was chemically linked to EENVEHDA and DDEHVEEPTVA repeat sequences of
      ring-infected erythrocyte surface antigen protein (an asexual blood-stage
      antigen) of Plasmodium falciparum. These synthetic constructs were tested for
      their humoral and cellular immune responses in five inbred strains of mice with
      different genetic backgrounds (H-2a, H-2b, H-2d, H-2k and H-2i). Mice immunized
      with these constructs showed higher antibody titres, secondary immune responses
      and antigen-induced T-cell proliferation compared with the peptide dimers alone.
      Sera from mice immunized with both the constructs inhibited merozoite invasion of
      erythrocytes in vitro by 60-80% at 1:10 antisera dilution. Polytuftsin alone
      proved to be a very poor immunogen in our studies, since no anti-tuftsin
      antibodies could be detected in the sera. Therefore, we conclude that the
      synthetic constructs described here could be useful for the development of
      subunit malaria vaccines.

PMID- 7526573
TI  - Characterization of binding and TNF-alpha-inducing ability of chitosans on
      monocytes: the involvement of CD14.
AB  - Chitosans with different chemical composition were found to induce TNF-alpha
      production from human monocytes. Their ability to induce TNF-alpha was found to
      be highly dependent on neutral-solubility and molecular weight. Monoclonal
      antibodies against CD14 inhibited TNF-alpha production from monocytes stimulated
      with neutral-soluble chitosans. Binding studies indicated that
      lipopolysaccharides (LPS) and neutral-soluble chitosans share a binding site on
      monocytes which involves CD14. TNF-alpha production from monocytes stimulated
      with chitosans was dependent on serum. LPS-binding protein (LBP) enhanced the
      chitosan-induced TNF-alpha production only to a minor degree, suggesting that
      serum proteins other than LBP play an important role in the stimulatory effect.

PMID- 7526575
TI  - Investigation of blood-brain barrier permeability by means of computerized image
      analysis.
AB  - Intravital fluorescence microscopy has been widely used to study changes of blood
      brain barrier (BBB) permeability in vivo. However, quantification of tracer
      extravasation by counting leaky spots provides only a rough estimate of
      permeability increase. We have therefore developed a new method for measurement
      of tracer extravasation from cerebral blood vessels by combining image analysis
      techniques with intravital fluorescence microscopy. This method is based on
      generation of subtraction images after shading and displacement correction.
      Subtraction images are further processed to eliminate noise and diminish
      artefacts due to vessel distortion and/or dilatation. The "degree of
      extravasation" (E(f) value) which is then calculated takes into account the
      number and size of leaky spots as well as their intensities. Examples are shown
      to illustrate that pure vasodilatation does not increase E(f) as long as the BBB
      permeability is not disturbed. This newly developed method may prove helpful for
      comparison of tracer extravasation under different experimental conditions.

PMID- 7526574
TI  - Deleterious effect of thimerosal on the potency of inactivated poliovirus
      vaccine.
AB  - High-potency inactivated poliovirus vaccine (eIPV) was combined with diphtheria
      tetanus-pertussis (DTP) vaccine containing thimerosal as a preservative to
      simulate the performance of a potential tetravalent vaccine. Neither type 1 nor
      type 3 poliovirus antigens appeared to be affected by thimerosal after exposure
      for 1 h at 37 degrees C as measured by enzyme-linked immunosorbent assay (ELISA).
      One epitope on the type 2 antigen was damaged within 5 min of exposure; however,
      the overall potency was unchanged when measured using a polyclonal antibody
      preparation. Exposure to thimerosal at 37 degrees C decreased the potency of all
      three poliovirus types to well below the level caused by heat deterioration alone
      in 1-2 days and to 0% after 16-17 days. At 25 degrees C, the potency of type 1
      poliovirus decreased by 46% in 1 day, whereas poliovirus types 2 and 3 were
      stable for 1 week. Storage of eIPV at 4 degrees C in the presence of thimerosal
      reduced the potency of type 1 poliovirus antigen to undetectable levels after 4-6
      months. Type 2 and 3 antigens were less markedly affected by 8 months of exposure
      to thimerosal at 4 degrees C. The loss of potency of type 1 as measured by ELISA
      was paralleled by a reduced level of neutralizing antibodies in mice injected
      with these preparations. The results obtained from testing eIPV in combination
      with DTP and thimerosal were generally similar to those obtained using eIPV with
      thimerosal. It remains to be seen to what extent thimerosal will affect the
      immunogenicity of eIPV in humans when injected as combined eIPV-DTP vaccine.

PMID- 7526576
TI  - [Membrane-physiologic reaction of arteriosclerotic coronary vessels to hypoxia in
      man].
AB  - Human coronary arteries were taken from heart transplant patients.
      Arteriosclerotic arteries were more depolarized and constricted over the whole
      PO2 range between 535 and 0 mmHg. During oxygen deficiency, control preparations
      showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation
      of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized
      by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. In normal coronary
      arteries, indomethacin reduced the hypoxic hyperpolarization and dilatation at 30
      mmHg PO2 by about 51%. The reduction was 26% in arteriosclerotic vessels. The
      complete removal of the endothelium caused a 49% (74%) restriction of dilatory
      vascular reactivity. The relationship was quite similar for a carbogen Krebs
      solution. The hyperpolarizing and dilatory contribution by prostacyclin was 32%
      in normal and 12% in arteriosclerotic coronary arteries. The remainder could be
      attributed to the basal release of the endothelial dilator endothelium-derived
      hyperpolarizing factor (EDHF). Thus it may be concluded that in arteriosclerotic
      blood vessels, prostacyclin (PGI2) synthesis and release are predominantly
      diminished. Finally, we found that the ratio PGI2/EDHF in the voltage and tension
      changes strongly shifted to the PGI2 side with a declining oxygen concentration.
      This is true for normal and arteriosclerotic vessels. In accordance with the
      activation curve for vascular smooth muscle, the hyperpolarization leads to
      relaxation via a closure of Ca2+ channels. Hyperpolarization of 2.5 mV reduces
      the tension developed by one-half. Minimal changes in cell polarization cause
      large changes in tissue perfusion.

PMID- 7526577
TI  - [A correlational approach to the comparison of nucleotide sequences].
AB  - A new method of evaluation of similarity between two nucleotide sequences is
      proposed. It is based on comparing frequency/correlation dictionaries of the
      sequences under investigation. The dictionary is a set of all strings of various
      length occurring within the sequences accompanied by their frequencies. The
      method proposed allows to compare sequences of arbitrary lengths, its advantage
      is absence of necessity of informal (expert) choice of the best fit. Efficiency
      of the method is demonstrated by comparison of several human genes and viruses.

PMID- 7526579
TI  - [Pseudomyxoma peritonei].
AB  - Pseudomyxoma peritonei is a rather rare disease manifested by layers of mucinous
      and gelatinous material deposited upon peritoneum, intestinum, and omentum majus.
      Surgical therapy proved to be the best treatment with many patients requiring
      multiple laparotomies. Either chemo- or immuno-therapy may be an adjuvant
      treatment for individual patients. Long-term nutritional support given in the
      late stages of disease provides a better quality of life during this period.

PMID- 7526580
TI  - Immunohistochemical distribution of keratin proteins in feline tissues.
AB  - The immunohistochemical distribution pattern of some keratin intermediate
      filament proteins has been analysed in a wide range of formalin fixed, paraffin
      embedded feline tissues using one polyclonal and two monoclonal antibodies raised
      against human keratins by means of the avidin-biotin-peroxidase complex
      technique. Only the epithelial and mesothelial cells were stained by the three
      antibodies, but differences in their corresponding staining pattern were noticed.
      The staining reaction of the polyclonal antibody raised against human skin
      keratin was found in both stratified and complex epithelia, while that of the
      monoclonal antibody which recognizes human keratins 8 + 18 + 19 of the Moll
      catalogue (NCL-5D3) was restricted to some simple epithelia. The staining
      reaction of the monoclonal antibody which reacts with human keratins 5 + 8 of the
      Moll catalogue (RCK-102) covered the widest spectrum of feline epithelial tissues
      analysed, including stratified, complex and simple epithelia. These staining
      patterns of feline tissues are basically similar with respect to those of
      corresponding tissues in other mammalian species, although some differences were
      also noticed and some obvious epithelial tissues were not stained. This study
      confirms the broad interspecies cross-reactivity of keratin proteins antibodies
      and demonstrates their capability to differentiate between various types of
      feline epithelia and some epithelial compartments.

PMID- 7526578
TI  - [Malignant tumors of the small intestine].
AB  - In a retrospective analysis, we studied 24 cases of malignant small bowel tumors.
      Apart from 9 cases of a carcinoid tumor, there occurred 6 cases of leiomyosarcoma
      and another 7 cases of adenocarcinoma. One case of malignant schwannoma and
      another case of lymphoma were also seen. Sonography and contrast-study of the GI
      tract were the decisive diagnostic tools. Nevertheless, months and even years
      elapsed before diagnosis was established. Only in 13 patients curative resection
      could be accomplished. In the remainder of patients, hepatic metastases were
      found or the tumor could not be resected any more owing to its size. In 6
      patients with synchronous and in 7 patients with metachronous liver metastases we
      carried out palliative regional intraarterial chemotherapy of the liver. The mean
      survival time of the whole patient group was 19 months. Patients, having
      submitted themselves to a complete resection of the tumor, had a significantly
      longer period of survival (mean survival time 25 months) in contrast to patients,
      having undergone a mere palliative operative procedure (mean survival time 14
      months). Mean survival time for leiomyosarcoma was 38 months, for adenocarcinoma
      14 months, and for carcinoid tumors 22 months. Owing to difficulties in
      establishing diagnosis, a tumor of the small intestine should be considered in
      any patient complaining of abdominal pain.

PMID- 7526581
TI  - Cerebellar terminations in the red nucleus of Macaca fascicularis: an electron
      microscopic study utilizing the anterograde transport of WGA:HRP.
AB  - The red nucleus (RN) of the macaque monkey is divided into a rostral two-thirds,
      the parvicellularis (RNp), which projects to the cerebellum by way of the
      inferior olivary nucleus, and a caudal third, the magnocellularis (RNm), which
      projects to the spinal cord via the rubrospinal tract. The RNp and RNm receive
      afferents from two principal sources: the cerebral motor cortices and the deep
      cerebellar nuclei. The terminations of these two afferent projections tend to be
      spatially segregated on rubral neurons, in that most corticorubral afferents
      terminate on more distal dendrites, and those from the deep cerebellar nuclei
      terminate more proximally. The present electron-microscopic analysis of the
      cerebellar terminations in the macaque RN provides anatomical evidence for the
      presence of labeled afferents in both divisions of this motor nucleus, following
      injection of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP)
      into the deep cerebellar nuclei and the anterograde transport of the tracer to
      the RN. The cerebellar terminal afferents are large; contain numerous
      mitochondria and primarily rounded synaptic vesicles; and form asymmetric
      synaptic contacts with rubral neurons. Unlike other terminals in the nucleus,
      they possess an electron-lucent cytoplasmic matrix and less densely packed
      synaptic vesicles. They are termed "large, round, pale" (LRP) terminals because
      of the morphological characteristics that distinguish them from other afferent
      terminal types found in RN. Labeled cerebellar afferents in RNp and RNm contact
      primarily neuronal somata, proximal dendrites emerging from the cell body, large
      diameter dendrites, and the spines of rubral neurons that arise from somata and
      proximal dendrites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526583
TI  - Topical bleomycin-dimethylsulfoxide in AIDS Kaposi's sarcoma.

PMID- 7526582
TI  - Expression of thrombospondin-1 (TSP1) and its receptor (CD36) in healthy and
      diseased human skin.
AB  - In the present study, an analysis was made of the expression pattern of
      thrombospondin-1 (TSP1) and its receptor (CD36) in skin biopsies obtained from
      healthy volunteers and from patients with lichen planus, lupus erythematosus,
      cutaneous T-cell lymphoma and psoriasis vulgaris. Using monoclonal antibodies
      against TSP1 in biopsies from the healthy volunteers and from both clinically
      involved and uninvolved skin of the patients, a specific peroxidase-positive
      reaction was detected around the sweat glands in the dermis. In all cases
      investigated, the CD36-positive lesional keratinocytes remained TSP1-negative.
      These findings favour the hypothesis that CD36-positive keratinocytes might have
      some functional relevance via oxidized low-density lipoprotein and/or collagen
      fibrils, without any connection with TSP1.

PMID- 7526586
TI  - Layoff--one year later. Interview by Linda McCloud Bondoc.

PMID- 7526585
TI  - Nitric oxide synthase (NOS) in the human umbilical cord vessels. An
      immunohistochemical study.
AB  - Localization of nitric oxide synthase (NOS) in endothelial cells of umbilical
      cord vessels and in cultured human umbilical vein endothelial cells was
      investigated by light and electron-microscopical (immunogold)
      immunohistochemistry. We observed localization of NOS-immunoreactivity in the
      majority (97%) of the endothelial cells of the umbilical vein and in a
      subpopulation (6.7%) of endothelial cells of the umbilical arteries. NOS was
      observed as well in the amniotic epithelium and in the cells of Wharton's jelly.
      Immunogold labelling in human umbilical vein endothelial cells dominated in the
      cellular matrix and was not associated with cellular organelles. Since human
      umbilical vessels are unique in lacking innervation, the functional significance
      of endothelium derived relaxing factor EDRF/NO in the local control of vascular
      flow is discussed.

PMID- 7526587
TI  - Antihistaminergic pretreatment prevents tissue extravasation of albumin from
      intra-abdominal trauma in rats.
AB  - Intra-abdominal surgery causes a loss of plasma into tissues within and around
      the abdomen, endangering tissue viability. Mast cells, containing histamine, are
      abundant in the abdominal cavity. In a model of mechanical intra-abdominal
      trauma, we investigated whether pretreatment with histaminergic H1 and H2
      receptor blockers counteracts this extravasation. In Wistar rats under chloralose
      anaesthesia, tissue clearances of labelled albumin were determined by a double
      isotope technique. Four groups were studied: Traumatized rats, pretreated (n =
      10) and non-pretreated (n = 9): non-traumatized rats; pretreated (n = 10) and non
      pretreated (n = 9). In the traumatized rats, given pyrilamine 10 mg kg-1 (H1)
      plus cimetidine 25 mg kg-1 (H2) just before the trauma, the blockers prevented
      the haemoconcentration from loss of plasma and the drop in arterial pressure
      during the very trauma procedure, observed among non-pretreated rats.
      Furthermore, they significantly decreased the clearance of albumin in the
      abdominal wall and the pancreas. In the non-traumatized animals, the blockers
      lowered arterial pressure and heart rate. In conclusion, the anti-histaminergic
      pretreatment decreased the trauma induced leakage of albumin, by mechanisms which
      may involve readjustments of pressures and flows in capillaries as well as a
      prevention of histamine effects on capillary permeability.

PMID- 7526590
TI  - Thalamic aphasia syndrome.
AB  - Eighteen patients (11 male, 7 female) with left thalamic haemorrhage confirmed by
      CT-scan of the brain were investigated for their language function. Aphasia Test
      for Turkish Citizens modified from Mayo Clinic Aphasia Test and Boston Diagnostic
      Aphasia Examination were given for evaluating the language modalities. Fluent
      aphasia was observed in 16 subjects (with paraphasia in 8 and hypophonia in 3).
      Dysarthric speech output was seen in 2 cases. Repetition and naming were well
      preserved while comprehension was moderately affected. This type of aphasia
      differs considerably from the classical aphasias and its rapid recovery is a very
      prominent feature.

PMID- 7526589
TI  - Histochemical demonstration of phospholipid containing choline in the cytoplasm
      of murine decidual cells.
AB  - The localization of lipids in the endometrium of virgin and 6- to 9-day-pregnant
      mice was detected by histochemical methods. Total lipids (as shown by staining
      with Sudan black) and phospholipids containing choline (PCC) were detected.
      Sections subjected to reactions that have been proposed for the demonstration of
      vitamins E and D and cholesterol gave negative results. In the virgin animals,
      lipids were found in epithelial cells but not in the endometrial storma. On the
      other hand in the pregnant animals, the endometrial stroma contained both Sudan
      black-stained lipids and PCC. Maximal staining was reached on day 8 of pregnancy.
      The staining was more conspicuous in the more differentiated decidual cells
      adjacent to the embryos than in the less differentiated predicidual cells. The
      nondecidualized stroma, situated peripherally near the myometrium did not stain
      for lipids. In the cytoplasm of decidual cells the reaction for PCC was observed
      in the form of granules, which were often arranged in groups surrounding the
      nuclei. We suggest that decidual cells store PCC to be mobilized as a precursor
      for mediators of decidualization, such as prostaglandins, that would act as
      paracrine inducers of the decidual reaction.

PMID- 7526591
TI  - Autoantibodies to myelin basic protein are not present in the serum and CSF of MS
      patients.
AB  - Myelin basic protein (MBP) is one of the main constituents of the CNS myelin
      sheaths, and an autoimmune response directed against MBP may be crucial in the
      demyelination process in patients with multiple sclerosis (MS). In this study
      sera and cerebrospinal fluid (CSF) from 25 MS patients, 25 patients with other
      neurological diseases and 16 healthy controls were examined for antibodies
      against MBP by using radio immunoblot, western blot, radio immunoassay and enzyme
      linked immunosorbent assay. No evidence for the presence of antibodies to MBP was
      found in sera or CSFs in either the MS patients, or in the control groups tested.

PMID- 7526588
TI  - Immunohistochemistry of two different types of placental fibrinoid.
AB  - The structure and composition of human placental fibrinoid were studied on
      cryostat and paraffin sections and by transmission electron microscopy as well as
      immunohistochemistry using antibodies directed against fibrin, fibronectin
      isoforms, collagens IV and VI, laminin and tenascin. The findings suggest two
      structurally and immunohistochemically different subtypes of fibrinoid: fibrin
      type fibrinoid and matrix-type fibrinoid. Fibrin-type fibrinoid was characterized
      by immunoreactivity for fibrin and cellular fibronectin, including the ED-A
      sequence. Immunostaining for all other extracellular matrix molecules was
      negative. Ultrastructurally, this fibrinoid subtype consisted of a meshwork of
      fibers with 20-nm cross striation typical of fibrin. Fibrin-type fibrinoid never
      contained extravillous trophoblast cells. It is therefore primarily a blood clot
      product derived from maternal and fetal blood. In contrast, matrix-type fibrinoid
      showed virtually no evidence of fibrin; it was immunopositive for extracellular
      matrix molecules such as the fibronectins, particularly oncofetal fibronectin
      (containing the ED-B sequence), collagen IV, laminin and tenascin. Oncofetal
      fibronectin, which was neither expressed in fibrin-type fibrinoid nor in the
      villous stromal core, seemed to be a specific marker for matrix-type fibrinoid.
      Single or clustered nonproliferative extravillous trophoblast cells were embedded
      within the matrix molecules. It is very likely that these cells secrete the
      matrix in a non-polarized fashion. Fibrin-type fibrinoid would appear to be
      involved in shaping the intervillous space and in replacing damaged
      syncytiotrophoblast acting as a transport and immune barrier. Matrix-type
      fibrinoid, as a secretory product of the extravillous trophoblast, should be
      discussed in context with the invasive properties of this cell population.

PMID- 7526592
TI  - Neurogenic muscle hypertrophy in radiculopathy.
AB  - The course of radiculopathy is sometimes associated with weakness and wasting of
      muscles. Very rarely in such cases, however, is hypertrophy of muscle fibres
      observed. Three cases are presented of sciatica with enlarged calves caused by
      hypertrophy of type 1 or types 1 and 2 muscle fibres. In light of the literature
      and the results obtained, an attempt is made to explain the cause of rare
      clinical symptoms and draw attention to diagnostic and therapeutic difficulties.

PMID- 7526595
TI  - Subcutaneous growth of human acoustic schwannomas in athymic nude mice.
AB  - In order to develop an in vivo model for growth of acoustic schwannomas, we
      studied tumor specimens from 10 patients, transplanted into a subcutaneous pocket
      of 67 nude mice. The number of tumors which survived or grew was 63 (94%).
      Obvious macroscopic growth was observed in 22 (33%), status quo in 28 (42%), and
      regression of tumor size in 13 (19%). The tumor disappeared in 4 cases (6%).
      Serial implantation was not possible due to the small amount of neuroma tissue in
      the surviving tumors. In animals with obvious macroscopic growth,
      neovascularization was clearly demonstrated. The presence of Schwann cells in the
      implants was confirmed immunohistochemically. The proliferative activity in the
      original and implanted tumors was evaluated by the proliferating cell nuclear
      antigen (PCNA) and Ki-67 nuclear antigen stainings and showed good correlation
      between primary tumors and implants. This in vivo tumor model will open new
      opportunities to study the biology of acoustic tumors and to test different
      therapeutic modalities.

PMID- 7526594
TI  - Localization of hyaluronan in the human endolymphatic sac. A study using the
      affinity hyaluronan binding protein.
AB  - This study was undertaken with the aim of localizing hyaluronan (hyaluronic acid,
      HYA) in tissue sections of the human endolymphatic sac by use of a hyaluronan
      binding affinity protein and the avidin-biotin/peroxidase staining procedure.
      Five human endolymphatic sacs were removed during surgery for acoustic neuroma.
      After microwave-aided fixation and decalcification, paraffin-embedded sections
      were prepared by routine histological methods. HYA was detected in some of the
      intraluminal substance as well as in parts of the epithelial lining, mainly in
      the rugose portions of the endolymphatic sac. HYA was observed intracellularly in
      epithelial cells. It was also found in the subepithelial tissue near the
      epithelia and close to the bony aqueduct. The distribution of HYA was uneven at
      all locations. The finding of HYA within the human endolymphatic sac may imply
      that this substance has important functions in the control of inner ear fluid
      homeostasis.

PMID- 7526596
TI  - Experimental cholesteatoma in the rat.
AB  - The etiology of cholesteatoma is still enigmatic. Of the current theories, none
      has been confirmed with adequately convincing evidence. A completely suitable
      animal model has not hitherto been available and there is still a need for
      further experimental studies of this entity. As a possible experimental model we
      suggest dimethyl-benzanthracene induced cholesteatoma in the rat.

PMID- 7526597
TI  - Nucleolar organizer regions in tongue carcinomas induced in rats: comparison with
      DNA cytofluorometric analysis.
AB  - Eleven papillomas and 25 carcinomas were induced in rat tongues by oral
      administration of 0.001% 4-nitroquinoline 1-oxide (4NQO) in drinking water, and
      the biological characteristics and proliferative activity of the tumors were
      investigated by both DNA cytofluorometry and the argyrophilic nucleolar organizer
      region (AgNOR) staining method. The histopathological characteristics, the mean
      number of AgNORs per cell and DNA ploidy patterns were compared. The mean AgNOR
      number was lowest in normal epithelium (1.65 +/- 0.10), and highest in squamous
      cell carcinomas (2.97 +/- 0.70) and intermediate in papillomas (1.87 +/- 0.28).
      The differences were statistically significant. All normal epithelium and all
      papillomas showed a diploid pattern. Eighteen (72%) of 25 squamous cell
      carcinomas showed a diploid pattern, while 7 (28%) showed a diploid plus
      tetraploid pattern. There was a significant difference in the mean AgNOR number
      between the two ploidy groups of squamous cell carcinomas. These results suggest
      that the mean AgNOR number may reflect the histological grade in the process of
      carcinogenesis and polyploidization of carcinomas.

PMID- 7526598
TI  - [Effects of tetrandrine on cytosolic free calcium in fetal rat cerebral cells].
AB  - Cytosolic free Ca(2+)-[Ca2+]i was measured in dissociated cerebral cells isolated
      from fetal rats using the fluorescent indicator Fura-2. Increases in [Ca2+]i
      occurred rapidly following exposure of the cells to 50 mmol.L-1 KCl, 10(-7) mol.L
      1 Bay K 8644 and 200 mumol.L-1 glutamate (Glu). [Ca2+]i elevation produced by
      K(+)-depolarization was blocked completely by pretreatment with tetrandrine (Tet)
      of various concentrations (10(-9) - 10(-7) mol.L-1, final). Tet showed
      significant inhibitory effect on [Ca2+]i increases stimulated by Glu in
      concentration-dependent manner. With Tet 10(-7) mol.L-1, Bay K 8644-induced
      increases in [Ca2+]i were reduced markedly. These results indicate that Tet can
      block the increases in [Ca2+]i in fetal rat cerebral cells induced by Ca2+
      agonists, suggesting that this drug may have a protective effect on cerebral cell
      injury.

PMID- 7526599
TI  - Epitopes recognized by anti-reduced and alkylated acetylcholinesterase
      antibodies.
AB  - Peptides of the reduced and alkylated acetylcholinesterase (RA-AChE) from the
      electric organ of Torpediniformes Torpedo torpedo subjected to bromo-cynogen
      (CNBr) cleavage or/and peptic digestion conserved well the antigen-antibody
      reactivity with anti-RA-AChE monoclonal antibodies E9, F6, and F12, whereas
      peptides produced by CNBr and tryptic treatments lost all the reactivity.
      Periodate oxidation of the RA-AChE or glycopeptidase digestion of the CNBr
      cleaved RA-AChE did not change the antigen-antibody reactivity. It implied that
      the epitopes recognized by the 3 anti-RA-AChE monoclonal antibodies are all
      peptide determinants rather than carbohydrate determinants.

PMID- 7526601
TI  - [4-Aminopyridine-induced licking response and histamine liberation in mice].
AB  - 4-Aminopyridine (4-AP) 1 mg.kg-1 sc at the scruff induced a licking response in
      mice. H1 receptor blockaders, such as diphenhydramine HCl (1, 10 mg.kg-1, sc at
      the scruff or 40 mg.kg-1, i.p.), chlorphenamine maleate (20 mg.kg-1, i.p.), and
      astemizole (2 mg.kg-1, i.g.), inhibited the licking response caused by 4-AP.
      Repeated injections of 4-AP (1 mg.kg-1) reduced the times of lick and the
      histamine content in the skin of injected site. 4-AP also promoted histamine
      release from incubated mouse peritoneal mast cells (PMC) in a dose-dependent
      manner. The results indicate that the licking response may originate from the
      histamine liberation of mast cells.

PMID- 7526600
TI  - [Releases of bradykinin and substance P by heating hind paw of rat].
AB  - Contribution of kallikrein-kinin system to heat-induced substance P (SP) release
      into the periphery was studied by using plasma kininogens-deficient strain Brown
      Norway Katholiek (B/N-Ka) and normal strain Brown Norway Kitasato (B/N-Ki) rats.
      Bradykinin (BK) and SP levels in the sc perfusates of the hind instep were
      measured by radioimmunoassay. In B/N-Ki rat, immersion of hind paw into hot water
      (47 degrees C) for 20 min led to an increase of BK (43 +/- s 34 fmol.min-1) and
      SP (11.1 +/- 9.7 fmol.min-1) in the perfusate, whereas those in B/N-Ka rat (BK
      1.3 +/- 1.0 fmol.min-1 (P < 0.01), SP 5.5 +/- 3.5 fmol.min-1 (P < 0.05)) were
      remarkably less. Heat-induced extravasation (leakage of Evans blue) in B/N-Ka rat
      was also less than that in B/N-Ki rat (P < 0.05). Results suggest that kallikrein
      kinin system is involved in the release of SP into the periphery, ie, BK released
      into the extravascular space by noxious heat stimulation intervenes in SP
      release.

PMID- 7526593
TI  - Neuropeptide Y inhibits adenylyl cyclase activity in rabbit retina.
AB  - Neuropeptide Y is known to be present in significant amounts in the retina of
      most vertebrates, but its physiological actions are largely unknown. We have
      therefore studied its effects on the intracellular cyclic AMP accumulation in
      rabbit retina. Neuropeptide Y had no effect on the basal cyclic AMP level but was
      found to inhibit the forskolin induced cyclic AMP accumulation. There were no
      differences between the effects of neuropeptide Y 1-36 and neuropeptide Y 13-36
      (2.4 x 10(-6) M) suggesting the presence of the Y2 subtype of neuropeptide Y
      receptor. D-myo-inositol-1,2,6-trisphosphate, a novel neuropeptide Y-antagonist,
      reduced per se the forskolin induced cyclic AMP production. The pronounced
      inhibitory effect of neuropeptide Y on the forskolin induced cyclic AMP
      production was, on the other hand, totally abolished by D-myo-inositol-1,2,6
      trisphosphate. The results indicate that neuropeptide Y acts on Y2 receptors in
      the retina to cause an inhibition of the adenylyl cyclase activity which could be
      antagonized by D-myo-inositol-1,2,6-trisphosphate. Such an inhibitory action of
      neuropeptide Y is similar to what has been found in brain tissue, but it has not
      previously been reported in the retina for neuropeptide Y or any of the other
      retinal neuropeptides.

PMID- 7526602
TI  - Protein metabolism in brain and muscle tissues of Mus booduga following repeated
      oral benzenehexachloride feeding.
AB  - Protein metabolism was studied in the brain and muscle tissues of mice, Mus
      booduga after administering orally 50 mg/kg body weight of benzenehexachloride
      (BHC) daily for 1, 5 and 15 days. Both tissues exhibited considerable decline in
      all the protein fractions such as total, soluble and structural proteins. This
      corroborates with the increased levels of free amino acids (FAA) and protease. To
      fortify these alterations, elevation in the activities of aspartate
      aminotransferase (AAT), alanine aminotransferase (AlAT) and glutamate
      dehydrogenase (GDH) were noticed. The two nitrogenous end products namely,
      ammonia and urea levels were also increased. These results clearly demonstrate
      the impairment of protein metabolism due to sublethal BHC toxicity.

PMID- 7526604
TI  - Isolation of acini from nasal glands of the guinea-pig.
AB  - A procedure for isolating the acinar cells of the serous gland in the mammalian
      nasal septum has been developed. This technique is characterized by meticulous
      and selective isolation with minimal contamination by the surface epithelial
      cells and employs enzymatic treatment with collagenase. The isolated cells were
      confirmed to be serous gland acini as shown by negative staining with Alcian blue
      and a high electron density of the granules. The acini were more than 90% viable
      as judged by trypan blue exclusion. Ultrastructural integrity of the cells was
      well maintained following the isolation procedure. Application of acetylcholine
      to the isolated acini induced an inward current in a whole-cell patch clamp and
      increased intracellular Ca2+ concentration measured by fura-2. These
      acetylcholine responses were completely blocked by atropine. These physiological
      findings directly demonstrated that nasal gland acini possess muscarinic
      activated receptors as previously suggested. These isolated cells hold promise
      for the in vitro study of secretory mechanisms in the mammalian nasal gland.

PMID- 7526603
TI  - Gi-mediated muscarinic adenylyl cyclase inhibition in timolol-treated stunned
      porcine myocardium.
AB  - The Gi-mediated muscarinic receptor-adenylyl cyclase system was examined in
      stunned myocardium induced by either three or five brief ischaemic periods after
      beta-adrenoceptor blockade by timolol (0.1 mg kg-1). The mid-left anterior
      descending coronary artery was occluded for 2, 10 and 2 min in four pigs, and for
      2, 2, 5, 10 and 2 min in four other pigs. All the ischaemic periods were
      separated by 30 min of reperfusion and the biopsies were obtained 60 min after
      the last ischaemic period. Segment length function was measured in the ischaemic
      region and in the control region supplied by the left circumflex artery. In the
      two groups, the percentage systolic shortening was reduced equally, to 59 +/- 9
      and 58 +/- 10% of control in the region subjected to ischaemia and only minimally
      in the control region. The biopsies from the stunned region from both groups
      showed: (1) no change in either the affinity for carbachol or the number of
      binding sites of the muscarinic receptors; (2) no alterations in messenger RNA
      encoding for the alpha subunit-2 of the inhibitory guanine nucleotide binding
      protein, as demonstrated by northern blot and solution hybridization; (3) no
      change in membrane-bound inhibitory guanine nucleotide binding protein, as shown
      by enzyme immunoassay utilizing a specific anti-peptide antibody, and (4)
      unchanged inhibition of stimulated adenylyl cyclase activity. These results
      suggest that there is an intact inhibitory guanine nucleotide binding protein
      mediated muscarinic receptor adenylyl cyclase system in the stunned porcine
      myocardium.

PMID- 7526606
TI  - Serum factors and hydrocortisone influence the synthesis of myelin basic proteins
      in mouse brain primary cultures.
AB  - Mouse brain primary cultures were used to study the influence of serum factors
      and hydrocortisone on myelin basic protein (MBP) gene expression. Serum factors
      increased the synthesis of the MBP isoforms in 18-day and older cultures.
      Synthesis of the 17 and 18.5 kDa MBPs steadily increased from 14 to 26 DIV (days
      in vitro). Synthesis of the 14 kDa MBP reached a peak at 22 days, after which it
      fell off rapidly. Addition of serum to the medium also stimulated MBP mRNA
      expression. However, in the presence of serum, maximal stimulation of MBP mRNA
      expression occurred at 16-20 days, significantly earlier than maximal stimulation
      of 17 and 18.5 kDa MBP synthesis by serum. These observations suggest that serum
      influences both transcriptional and post-transcriptional steps in the expression
      of the MBP genes in primary cultures. Hydrocortisone increased the synthesis of
      the 14, 18.5 and 17 kDa MBP isoforms by two- to three-fold. This effect was seen
      in cultures older than 15 DIV. This effect of hydrocortisone on the synthesis of
      the MBPs may be responsible for the increase in the steady state levels of MBP in
      the presence of hydrocortisone. These studies suggest a role for serum factors
      and hydrocortisone in the transcriptional and post-transcriptional steps of MBP
      gene expression. They also suggest that this role may be developmentally
      regulated.

PMID- 7526607
TI  - Norepinephrine modulates excitatory amino acid-induced responses in developing
      human and adult rat cerebral cortex.
AB  - These experiments were designed to assess the ability of norepinephrine and its
      beta-receptor agonist, isoproterenol, to modulate responses induced by activation
      of excitatory amino acid receptors in brain slices obtained from developing human
      cortex or adult rat cortex. Human cortical slices were obtained from children
      undergoing surgery for intractable epilepsy (9 months to 10 yr of age). For
      comparison, slices were also obtained from rats (2-3 months of age).
      Iontophoretic application of glutamate, N-methyl-D-aspartate or alpha-amino-3
      hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) produced excitatory responses
      consisting of membrane depolarizations accompanied by action potentials.
      Iontophoretic or bath application of norepinephrine or isoproterenol enhanced
      responses evoked by glutamate or N-methyl-D-aspartate. Depolarizations occurred
      with shorter latencies and their amplitudes increased. Action potential frequency
      was also increased and responses were of longer duration. In contrast,
      norepinephrine or isoproterenol had no effect on responses induced by AMPA. The
      enhancement of responses induced by N-methyl-D-aspartate or glutamate was
      antagonized by the beta-adrenergic receptor antagonist propranolol. Similar
      findings were obtained from neurons in humans or rats. These results suggest that
      norepinephrine, possibly via beta-receptors, potentiates responses mediated by
      glutamate and N-methyl-D-aspartate receptors without affecting those mediated by
      AMPA receptors. These effects were observed at all ages studied, indicating that
      the ability of norepinephrine to modulate excitatory neuronal transmission is
      well developed in human cortex by 9 months of age.

PMID- 7526608
TI  - Gene expression in astrocytes is affected by subculture.
AB  - We have investigated the effects of cell passaging and time in culture on
      astrocyte morphology, transferrin expression and the expression of two main
      astrocyte markers, glial fibrillary acidic protein (GFAP) and glutamine
      synthetase (GS: EC 6.3.1.2). When primary astrocytes were subcultured, giving
      rise to secondary and tertiary cultures, their morphology changed, regardless of
      the split ratio used to passage the cells. Correlating with this morphological
      change, a dramatic increase in the accumulation of GFAP and GS mRNAs was observed
      after cells had been passaged. This effect was in marked contrast to the moderate
      increase in the levels of GFAP and GS mRNAs observed over several weeks in
      primary culture. Hydrocortisone induction of GS gene expression was not affected
      by cell passage. Transferrin mRNA, which is not normally found in astrocytes in
      vivo, was expressed at a high level in primary cultures of astrocytes. However,
      transferring mRNA almost completely disappeared after the second passage.
      Astrocyte-conditioned media, or co-cultures with oligodendrocytes, modified
      transferrin gene expression. Taken together, these results show that subculturing
      of primary rat astrocytes leads to a dramatic change in the genetic expression of
      several proteins and provides a new approach to modify astrocyte differentiation
      in vitro.

PMID- 7526605
TI  - Neuropathology of twitcher mice: examination by histochemistry,
      immunohistochemistry, lectin histochemistry and Fourier transform infrared
      microspectroscopy.
AB  - The twitcher mouse is an authentic animal model of globoid cell leukodystrophy,
      which is a genetic disease that affects the lysosomal enzyme galactocerebroside
      beta-galactosidase. This enzyme deficiency causes one of its substrates,
      galactosylsphingosine (psychosine), to accumulate in myelin-forming cells, which
      eventually results in their death. In the central nervous system, the death of
      oligodendrocytes is thought to cause a series of secondary pathological changes.
      In this study, several techniques were utilized to examine the neuropathology of
      two different brain regions in the twitcher mouse--the hindbrain and the
      cerebrum. Neuropathological changes were as follows: (1) demyelination was
      detected in the hindbrain but not in the cerebrum, (2) a high density of periodic
      acid-Schiff-positive cells were detected in the hindbrain and to a lesser extent
      in the cerebrum, (3) astrocyte gliosis was pronounced in both the hindbrain and
      cerebrum, and (4) macrophages were abundant in both the hindbrain and the
      cerebrum. We found that Periodic acid-Schiff-positive cells, astrocyte gliosis
      and macrophage infiltration were present in white and gray matter regions of the
      cerebrum, while they were generally absent from the granule and molecular layers
      of the cerebellum. In addition to these studies, we utilized the technique of
      Fourier transform infrared (FT-IR) microspectroscopy to identify the in situ
      distribution of psychosine in the brains of twitcher mice. Evidence was obtained
      that indicates a large accumulation of psychosine in the hindbrain, and to a
      lesser extent in the white matter of the cerebrum in the twitcher mouse, but not
      the normal mouse. There was no evidence for the accumulation of psychosine in the
      molecular layer of the cerebellum from the twitcher or normal mouse. Our
      conclusions are as follows: (1) pathology is more advanced in the hindbrain
      compared to the cerebrum, which is likely due to the hindbrain becoming
      myelinated prior to the cerebrum, (2) demyelination is not necessary for the
      development of secondary pathological changes, (3) pathology is not limited to
      white matter in the cerebrum, (4) pathology is not present in all brain regions,
      i.e. the granule and molecular layers of the cerebellum are devoid of
      pathological changes, and (5) psychosine accumulates in both the cerebrum and
      hindbrain, but not in the molecular layer of the cerebellum in the twitcher
      mouse. This study demonstrates that FT-IR microspectroscopy can be used to
      correlate chemical changes to histopathological changes in brains from twitcher
      mice, which suggests that FT-IR microspectroscopy may be a useful tool for
      studies examining other brain diseases.

PMID- 7526609
TI  - Mechanism of interferon action. Translational control and the RNA-dependent
      protein kinase (PKR): antagonists of PKR enhance the translational activity of
      mRNAs that include a 161 nucleotide region from reovirus S1 mRNA.
AB  - The interferon-inducible, RNA-dependent protein kinase (PKR) is an important
      regulator of viral protein synthesis. Activated PKR inhibits protein synthesis by
      phosphorylating initiation factor eIF-2 alpha. The reovirus S4 gene, whose 1196
      nucleotide mRNA transcript does not activate the PKR kinase, is efficiently
      expressed in vector-transfected monkey COS cells. By contrast, the 1463
      nucleotide S1 gene of reovirus, which is a potent activator of PKR, is poorly
      expressed in COS cells. Virus genetic engineering was therefore used to examine
      the effect of the PKR activator sequence from the reovirus S1 gene on the
      expression of chimeric genes of reovirus in transfected COS cells. Chimeric S1/S4
      and S4/S1/S4 reovirus constructions that included the PKR activator sequence from
      S1 in the sigma 3 ORF of S4 were expressed much less efficiently than wild-type
      S4. However, expression of sigma 3 from S4 (3'UTR/S1), which included the PKR
      activator sequence from S1 within the 3'-UTR of S4, was comparable to that from
      wild-type S4. Treatment of COS cells with 2-aminopurine, an inhibitor of PKR,
      increased the expression of the reovirus S1, S1/S4, and S4/S1/S4 chimeric genes
      but not the S4 gene or S4 (3'UTR/S1) chimera in transfected COS cells. Likewise,
      coexpression of the phosphotransfer-negative mutant PKR (K296R) increased the
      expression of reovirus S1, S1/S4 and S4/S1/S4 chimeric genes but not the S4 gene
      or S4 (3'UTR/S1) chimera in cotransfected COS cells. Truncated PKR(1-243) which
      includes the dsRNA binding domain but not the kinase catalytic subdomains was
      able to enhance the expression of reovirus S1, but did not affect S4 expression.
      The dsRNA binding protein E3L encoded by vaccinia virus also increased S1
      expression similar to PKR (1-243) and PKR(K296R). These results suggest that the
      translational repression in vivo mediated by PKR is selective for mRNAs that
      possess the kinase activator region, and that the dominant negative effect of PKR
      on gene expression is likely mediated by the RNA binding activity of the PKR
      protein.

PMID- 7526610
TI  - A number of osteocalcin antisera recognize epitopes on proteins other than
      osteocalcin in cultured skin fibroblasts: implications for the identification of
      cells of the osteoblastic lineage in vitro.
AB  - Rabbit antisera to bovine osteocalcin were produced independently in two
      laboratories and their specificities established by western blot analysis. By
      immunohistochemistry each of the five polyclonal antisera produced an intense
      cytoplasmic staining in human bone-derived cells. Staining intensity was strongly
      attenuated by preabsorption of the antisera with osteocalcin. No staining was
      observed using nonimmune rabbit serum. However, the choice of skin cells as
      negative controls for osteocalcin synthesis yielded an unexpected positive
      staining pattern similar to that seen with the bone-derived cells over a range of
      antiserum dilutions. This was not caused by the uptake of exogenous osteocalcin
      from the culture medium because a similar pattern of staining was observed when
      medium was supplemented with osteocalcin-depleted fetal calf serum. Treatment
      with 1,25-dihydroxyvitamin D3 induced osteocalcin mRNA expression and osteocalcin
      secretion in cultures of bone-derived cells but not in skin fibroblasts. The
      results demonstrate that these polyclonal antisera also recognize epitopes shared
      with other proteins synthesized in culture by skin fibroblasts. Furthermore,
      three mouse monoclonal antibodies to distinct regions of the osteocalcin molecule
      show differential staining of human bone-derived cells, skin cells, and
      osteosarcoma cells (MG63). These observations indicate that the shared epitope
      residues in the central region of osteocalcin and are consistent with the
      specific synthesis of osteocalcin by bone cells alone. The observed
      nonspecificity of many osteocalcin antisera may compromise immunocytochemical
      studies of the osteoblast phenotype in studies in vitro when based solely on
      reactivity with inadequately characterized osteocalcin antisera.

PMID- 7526611
TI  - Benefit of systemically administered rhIGF-I and rhIGF-I/IGFBP-3 on cancellous
      bone in ovariectomized rats.
AB  - The dose-related effects of systemically administered rhIGF-I and rhIGF-I/IGFBP-3
      were monitored in the osteopenic rat skeleton at three different sites with
      cancellous bone: distal femoral metaphysis, epiphysis, and lumbar vertebral
      bodies. At the age of 16 weeks, rats were bilaterally ovariectomized (OVX) or
      sham operated (sham) and 8 weeks later divided into the control groups (sham
      OVX), and OVX groups treated with different doses of rhIGF-I or rhIGF-I/IGFBP-3
      for 8 weeks. Fluorescent bone markers were given 9 and 2 days before necropsy. In
      addition, changes in designated bone sites as a result of ovariectomy alone were
      evaluated 8 and 16 weeks after surgery. High bone resorption, which dominates the
      postovariectomy remodeling process, resulted in a loss of cancellous bone at all
      measured sites. The highest trabecular bone loss was measured in the metaphyses
      (40%), compared with 22% in the lumbar vertebrae and 16% in the epiphyses. After
      8 weeks of treatment with 7.5 mg/kg of rhIGF-I/IGFBP-3, bone formation rates were
      increased at all sites measured. Increased trabecular thickness was observed at
      the epiphyses and in the lumbar vertebral bodies. Increased bone resorption was
      restricted to the metaphyses of the rats that received the highest dose of rhIGF
      I or rhIGF-I/IGFBP-3. Both formulations of rhIGF-I increased longitudinal bone
      growth similarly. This experiment demonstrates site-specific differences in
      cancellous bone reactions following ovariectomy. Epyphyses showed some advantages
      for cancellous bone histomorphometry over metaphyses and lumbar vertebral bodies.
      The data presented confirm the potential of rhIGF-I/IGFBP-3 complex to promote
      the bone formation process at various bone sites in osteoporotic rat skeleton.

PMID- 7526612
TI  - Identification of a new restriction endonuclease R.NciII, from Neisseria cinerea.
AB  - Site-specific restriction endonuclease R. Nci II has been purified from Neisseria
      cinerea strain 32615. The enzyme recognizes the sequence 5' GATC 3' and its
      activity is inhibited by the presence of methylated adenine residue within the
      recognition sequence.

PMID- 7526613
TI  - The occurrence of siderophores in staphylococci.
AB  - In 180 staphylococcal strains of diverse origin belonging to 26 species a
      hydroxamate class siderophore was detected with chemical test. In 65% of
      investigated strains it was identified by biological assay as aerobactin. A
      correlation between hydroxamate siderophore production, species affiliation and
      pathogenicity was not found. In 14 (7.8%) strains a catechol class siderophore,
      beside aerobactin, was detected.

PMID- 7526614
TI  - Occurrence, purification and properties of the staphylococcal beta
      hydroxybutyrate dehydrogenase.
AB  - beta-Hydroxybutyrate dehydrogenase (EC 1.1.1.30.)-an enzyme involved in
      degradation of polymer store material-was found in staphylococci. The enzyme was
      isolated from Staphylococcus xylosus NCTC D100694 cells, purified and
      characterized. The native enzyme is a tetramer and consists of equal subunits.
      Its relative molecular mass is M(r) = 140 kDa and pI = 4.7. The enzyme activity
      is stimulated by Mg+2 and Ca+2 ions. Staphylococcal beta-hydroxybutyrate
      dehydrogenase is relatively stable and active in a wide temperature range. The
      optimum pH for oxidation is 8.6 and for reduction 6.7. The enzyme is highly
      specific for D(-)stereoisomer of beta-hydroxybutyrate. Km values for beta
      hydroxybutyrate and acetoacetate are 39.1 microM and 5.47 microM, respectively.

PMID- 7526615
TI  - Comparison of utilization of pectins from various sources by pure cultures of
      pectinolytic rumen bacteria and mixed cultures of rumen microorganisms.
AB  - Utilization of citrus, lucerne, apple and sugar beet pulp pectins by pure strains
      of rumen bacteria, Prevotella ruminicola, Lachnospira multiparus and Butyrivibrio
      fibrisolvens was compared. Additionally, the utilization of pectins by mixed
      rumen microorganisms was evaluated. The comparison was based on the depletion of
      galacturonic acid from medium, content of cellular protein in the cultures and
      the amount of end products of pectin fermentation in cell-free culture fluids. It
      was found that citrus pectin was utilized best; utilization of lucerne, apple and
      sugar beet pectins was dependent on the species of bacteria. P. ruminicola and B.
      fibrisolvens utilized polygalacturonic acid from sugar beet pectins better than
      that from apple or lucerne pectin, while L. multiparus was capable of
      significantly better utilization of lucerne pectin than pectin from sugar beet or
      apple. The source of pectin was less important for mixed cultures of rumen
      microorganisms than for pure cultures of rumen bacteria. The amount of
      fermentation products in the culture fluids supported the conclusion that citrus
      pectin was utilized better than others. Microbial protein content in the cultures
      was found to be a less sensitive indicator of pectin utilization than the
      remaining examined parameters. P. ruminicola strains and mixed cultures of rumen
      microorganisms were shown to have the highest ability to utilize pectins, L.
      multiparus-moderate, while the B. fibrisolvens strains utilized pectin the least.

PMID- 7526616
TI  - Selection of strain, culture conditions and extraction procedures for optimum
      production of beta-galactosidase from Kluyveromyces fragilis.
AB  - Among 47 tested yeast strains, belonging to different genera, only two cultures
      of Kluyveromyces fragilis and Fabospora fragilis showed beta-galactosidase
      activity in shaken flasks. Three types of extraction were used to release the
      enzyme from K. fragilis cells: solvent and detergent extraction, freezing and
      thawing extraction, and mechanical disintegration prior to extraction, using
      Triton X-100. The results indicate that the highest yield could be obtained by
      mechanical disintegration of cells. Factors affecting the enzyme production were
      studied using fermentation media of different chemical composition. The medium
      containing lactose, salts and yeast extract with initial pH 7.0 was selected as
      the best for enzyme production. Monobasic ammonium phosphate (2.0 g/dm3) was
      found to be the best inorganic nitrogen source for enzyme production. The effect
      of phosphorus level was also studied.

PMID- 7526617
TI  - Egg shell penetration tendency of different Salmonella serotypes by attached ring
      color method.
AB  - To investigate the extent of Salmonella penetration through the egg shell, 200
      eggs were dipped in red (for 3 minutes) and then in green (for 6 minutes) aqueous
      bland food color solution for the detection of positive penetration test areas.
      Each egg with positive penetration area, 5 spots of 1 cm in diameter, was marked
      for the attachment of steel cylinders (1 cm in diameter and height). These
      cylinders were filled with the test strain of Salmonella. Among 19 serotypes S.
      pullorum and S. gallinarum were nonmotile while the other 17 were motile. Among a
      total of 180 eggs (900 points) maximum (30%) penetration was in area III, where
      salmonellae invaded through cuticle, shell, inner and outer shell membranes,
      followed by area II (14.77%) and area I (4.6%). It was very well evident that
      penetration of salmonellae to the contents of eggs was maximum, while in area II
      the penetration was to outer shell membrane and in the least cases through the
      cuticle and shell. Penetration in area I is not significant and to some extent in
      area II as well, while invasion in area III is highly significant.

PMID- 7526618
TI  - Gibberellic acid production by Fusarium moniliforme on lupin seed extract.
AB  - Fusarium moniliforme grown on extract obtained from lupin (Lupinus angustifolius
      L.) seeds effectively produced gibberellic acid (GA3). The extract used at the
      concentration of 8.3-0.41% d.w. inhibited the fungal growth. As much as 0.35-0.40
      g of GA3 per liter was produced on the 2% extract. The latter medium competes
      effectively with other media used so far for GA3 production.

PMID- 7526619
TI  - RNA-binding proteins in prokaryotes.

PMID- 7526621
TI  - Molecular biology of blood-brain barrier ontogenesis and function.
AB  - The vascular system of the central nervous system is derived from capillary
      endothelial cells, which have invaded the early embryonic neuroectoderm. This
      process is called angiogenesis and is probably regulated by brain-derived
      factors. Vascular endothelial cell growth factor (VEGF) is an angiogenic growth
      factor whose expression correlates with embryonic brain angiogenesis, i.e.
      expression is high in the embryonic brain when angiogenesis occurs and low in the
      adult brain when angiogenesis is shut off under normal physiological conditions.
      VEGF is also a vascular permeability factor (VPF) and, therefore, its expression
      is also consistent with the formation of the blood-brain barrier by brain
      endothelial cells, i.e. capillaries are leaky in the embryonic brain but are
      tight in the postnatal and adult brain. Thus, VEGF/VPF may be a key factor
      regulating endothelial cell growth and permeability. This notion is further
      supported by the observation that VEGF expression is induced and strongly
      upregulated in human malignant glioblastoma. This tumor is characterized by
      vascular proliferations, vascular leakage and edema. The differentiation of blood
      brain barrier endothelial cells is probably regulated by astrocytes which form
      foot processes apposed to the abluminal vascular basement membrane. Blood-brain
      barrier endothelial cells express a set of cell surface proteins that are absent
      from permeable capillaries. We have characterized one such novel transmembrane
      glycoprotein which is a new member of the immunoglobulin superfamily. This
      protein and the analysis of the in vitro characteristics of brain endothelial
      cells may help to define the molecular mechanisms that are involved in blood
      brain barrier induction and permeability.

PMID- 7526620
TI  - The toxicity of antigens extracted from strains of Bacteroides vulgatus from
      different origins to chicken embryos.
AB  - The toxicity of purified lipopolysaccharides (LPS) and capsular polysaccharides
      (CPS) extracted from 3 strains of Bacteroides vulgatus to 11 day old chicken
      embryos was examined. The three B. vulgatus strains were isolated from different
      sources. The CELD50 (chicken embryos lethal dose 50%) of these preparations was
      determined. All antigens were shown to be lethal to chick embryos. The toxicity
      of LPS of the strains isolated from clinical sources was higher than that of the
      capsular antigens. The LPS and CPS of one strain isolated from normal gut-flora
      was less toxic than other antigens.

PMID- 7526624
TI  - The effect of BAY K-8644 on cytotoxic edema induced by total ischemia of rat
      brain.
AB  - The calcium channel activator BAY K-8644, a dihydropyridine (DHP) derivative, has
      been shown to possess neurochemical and behavioral activities, but its effect on
      ischemic brain damage has remained unknown. This report describes the effect of
      the drug on the progression of cytotoxic edema induced by total ischemia of the
      brain, evaluated by measuring the time constant, k, of elongation of the 1H-NMR
      relaxation time (T2) after brain biopsy. Twenty-six male Wistar rats were divided
      into four groups, (a) control (saline) group (n = 10), (b) BAY K-8644 vehicle
      group (n = 4), (c) BAY K-8644 0.03 mg/kg group (n = 6) and (d) BAY K-8644 0.3
      mg/kg group (n = 6). The k value of group (d), 18.2 +/- 5.8 min (mean +/- SD),
      was significantly higher compared with those of groups (a) 10.3 +/- 1.6, (b) 11.8
      +/- 1.5 and (c) 9.8 +/- 3.3 min (p < 0.01 by ANOVA). These results indicate that
      BAY K-8644 delayed the progression of cytotoxic edema induced by total ischemia
      of the rat brain.

PMID- 7526622
TI  - Astrocyte swelling in liver failure: role of glutamine and benzodiazepines.
AB  - We examined the effect of methionine sulfoximine (MSO) and peripheral
      benzodiazepine (BZD) ligands on ammonia-induced swelling of primary astrocyte
      cultures. Swelling was completely abolished by co-treatment with MSO, an
      inhibitor of glutamine synthetase. We also established that many of the effects
      caused by ammonia, including the reduction in K+ uptake, increase in Cl- uptake
      and reduction in myo-inositol uptake were diminished by co-treatment with MSO.
      Agonists of the peripheral-type BZD receptor aggravated ammonia-induced swelling,
      whereas a peripheral BZD receptor blocker, PK 11195, diminished the extent of
      swelling. Our findings implicate glutamine and the peripheral-type benzodiazepine
      receptor in the pathogenesis of the edema associated with fulminant hepatic
      failure.

PMID- 7526623
TI  - Temporal profiles of Ca2+/calmodulin-dependent and -independent nitric oxide
      synthase activity in the rat brain microvessels following cerebral ischemia.
AB  - The present study was aimed at determining chronological alterations of
      Ca2+/calmodulin (CaM)-dependent and -independent nitric oxide synthase (NOS)
      activities in brain microvessels (MV) isolated from the affected hemisphere
      following an occlusion of the middle cerebral artery (MCAo) in rats. It was shown
      that significant enhancements of Ca2+/CaM-independent NOS activity to 922% and
      920% of control level were manifested at 4 h and 24 h, respectively, which
      returned to the control level at 48 h after MCAo. Regarding Ca2+/CaM-dependent
      NOS, on the other hand, it was shown that the activity was invariably increased
      to 374% and 743% of control level at 48 h and 1 week following MCAo,
      respectively. Thus, the present study provided the first evidence that two
      distinct types of NOS activities were increased with different temporal patterns
      after MCAo. These heterogeneous alterations of NOS activities may be of critical
      importance for the induction of brain damage following cerebral ischemia.

PMID- 7526625
TI  - The regulation of intracellular pH is strongly dependent on extracellular pH in
      cultured rat astrocytes and neurons.
AB  - We studied the mechanisms regulating intracellular pH (pHi) in cultured rat
      astrocytes and neurons, with particular reference to the influence of
      extracellular pH (pHe) on these mechanisms, using microspectrofluorometric
      monitoring from single cells, loaded with the pH-sensitive fluorophore BCECF. The
      pH regulatory mechanisms differ between neurons and astrocytes. The experimental
      data suggest the presence of a Na+/H+ and a Na(+)-independent HCO3-/Cl- exchanger
      in both types of cells, while astrocytes, in addition, utilise a Na(+)-dependent
      HCO3-/Cl- exchanger for regulating acid transients. In both cell types the pH
      regulatory mechanisms are strongly dependent on pHe. Thus, at pHe 6.85 or below,
      there was no recovery of pHi. Steady state pHi was also strongly dependent on
      pHe, in both astrocytes and neurons. The pHi recovery following normalisation of
      pHe was very rapid, (indicating that a prolonged exposure to a low pH stimulates
      pH regulating mechanisms), and was inhibited by 4,4'-diisothiocyanatostilbene
      2,2'-disulphonic acid (DIDS) and amiloride, or in the absence of Na+. The results
      challenge the concept of a H(+)-regulatory site solely at the internal side of
      the exchanger regulating pHi to a constant value.

PMID- 7526626
TI  - Selective increase in blood-tumor barrier permeability by calcium antagonists in
      transplanted rat brain tumors.
AB  - To clarify the altered response of calcium antagonists on pathological vessels,
      we investigated the effect of intracarotid infusion of nifedipine on the blood
      brain barrier (BBB) permeability using a rat glioma model. Animals were treated
      with 0, 0.1, 1, 5, and 10 micrograms/kg/min of intracarotid continuous infusion
      of nifedipine. 2% Evans blue (EB, 2 ml/kg) was injected intravenously immediately
      after nifedipine infusion. BBB and blood-tumor barrier (BTB) permeability were
      evaluated by direct visual and histological observation. During the entire
      experiment, systemic parameters such as arterial blood pressure and blood
      analysis were not changed significantly. There was a dose-dependent increase of
      EB permeability selectively in the tumor tissue without affecting the normal
      brain. These results indicate that tumor vessels may show an altered response to
      calcium antagonists. Intracarotid administration of calcium antagonists
      contribute to a selective enhancement of drug delivery to malignant brain tumors
      without affecting the normal brain.

PMID- 7526630
TI  - Adequate enzymatic substitution in treating exocrine pancreatic insufficiency.
AB  - The chymotrypsin in the stool test was used to monitor adequate enzymatic
      substitution in treating exocrine pancreatic insufficiency with 18 patients (16
      suffering from chronic pancreatitis and 2 having passed duodenopancreatectomy due
      to pancreatic cancer). This test helps to identify pancreatic insufficiency and
      can be successfully used in monitoring the adequate amount of pancreatic
      substitute, which, we have found, differs from patient to patient. The dosage can
      be higher in cases of chronic pancreatitis than in those required after
      duodenopancreatectomy.

PMID- 7526629
TI  - Involvement of nitric oxide and free radical (O2-) in neuronal injury induced by
      deprivation of oxygen and glucose in vitro.
AB  - Nitrix oxide (NO) is a free radical that has been recently proposed as a
      messenger molecule in the central nervous system. Since its involvement in
      glutamate neurotoxicity in vitro has been recently reported, using rat cortical
      cultures, we tested the hypothesis that NO also plays a role in neuronal injury
      induced by deprivation of oxygen and glucose. About 80-90% of neurons were killed
      in less than 12 h after a 4-6 h period of oxygen and glucose deprivation. N-nitro
      L-arginine (L-NNA), an inhibitor of nitric oxidase synthase (NOS), significantly
      ameliorated this neuronal injury in a dose dependent manner. Since it has been
      suggested that NO is inactivated in a short time period by interaction with
      superoxide anions (O2-), which are generated during ischemia-reperfusion in vivo,
      we further evaluated the effect of superoxide dismutase (SOD) on neuronal injury
      in this test system. SOD failed, however, to protect against neuronal death.
      Furthermore, concomitant addition of SOD and L-NNA rather reduced the beneficial
      effects of L-NNA. Our results suggest therefore that NO, at least in part,
      mediates neuronal injury secondary to deprivation of oxygen and glucose in vitro
      and that superoxide anions may have a protective role by inactivating NO.

PMID- 7526628
TI  - 7.2% NaCl/10% dextran 60 versus 20% mannitol for treatment of intracranial
      hypertension.
AB  - Severe head injury is frequently associated with extracranial injuries causing
      hemorrhagic hypotension. Volume replacement with isotonic fluids not only is
      therapeutically of limited efficacy but may aggravate posttraumatic brain edema.
      On the other side, hypertonic/hyperoncotic saline/dextran solution (HHS) shown to
      restore cardiovascular function in hemorrhagic shock instantaneously, was found
      to decrease intracranial pressure in experimental head injury. Currently the
      therapeutic efficacy of HHS and mannitol on ICP was compared at 24 hrs after a
      focal cerebral lesion and inflation of an epidural balloon in rabbits. Both
      solutions given at an equimolar dose rapidly lowered the ICP. After the first
      injection, ICP reduction was longer maintained with mannitol (189 +/- 27 min) as
      compared to HHS (98 +/- 14 min), while no difference in duration of lowering ICP
      was found after the second injection. Due to its blood pressure effects, HHS
      afforded a higher cerebral perfusion pressure than mannitol. In animals with HHS,
      the water content of the traumatized hemisphere was increased while the
      contralateral hemisphere was dehydrated. With mannitol, no differences in water
      content were found between the injured and uninjured hemisphere. The efficiency
      of HHS in hemorrhagic shock and intracranial hypertension render the fluid
      mixture particularly promising in patients with polytrauma in combination with
      head injury.

PMID- 7526627
TI  - Metabolic alterations accompany ionic disturbances and cellular swelling during a
      hypoxic insult to the retina: an in vitro study.
AB  - To study the ionic, metabolic, and morphologic derangements that occur following
      brain injury we utilized a retina in vitro model of hypoxia. Retinas were
      dissected into oxygenated (95% O2, 5% CO2) Ames medium, a physiologic solution
      resembling cerebrospinal fluid, and randomly assigned to either experimental
      hypoxic conditions (95% N2, 5% CO2) or control conditions. All retinas were
      incubated and maintained at 37 degrees C. Changes in extracellular K+ and lactate
      concentration, intracellular incorporation of 45Ca and 14C-leucine, uptake of
      glucose using [14C]-2-deoxy-D-glucose (2DG), and cell size were determined at 10,
      20, 30, and 60 minute time intervals. The results show that compared to control
      retinas hypoxia produced: (1) an early increase in extracellular concentration of
      K+ and lactate, (2) a delayed increase in the intracellular incorporation of
      45Ca, (3) an early onset of cellular swelling, and (4) a decrease in the
      intracellular incorporation of 14C-leucine, and (5) increased glucose
      utilization. All of the results were statistically significant (p < 0.05) and
      exhibited a dose response relationship with the exception of intracellular
      incorporation of 45Ca which did not become significantly different until 30
      minutes post-hypoxia. A 16% increase in cell size was noted after 10 minutes of
      hypoxia. Increased hypoxic cell size persisted for 30 minutes but after 60
      minutes the control retinas appeared enlarged as well. Our results suggest that
      ionic, metabolic, and morphologic derangements can be demonstrated utilizing an
      in vitro model of hypoxia which are similar to those seen following in vivo
      traumatic brain injury. With use of this model the mechanisms behind these ionic
      metabolic relationships can be addressed at the molecular level.

PMID- 7526632
TI  - [Comment on thermal and laser therapy].

PMID- 7526631
TI  - [Retrosternal esophagocoloplasty as current means of surgery for esophageal
      carcinoma].
AB  - The authors present an account of their experience with retrosternal
      oesophagocoloplasty as a palliative by pas in inoperable carcinoma of the
      oesophagus. They differentiate secondary and primary indications. So far they
      used this operation in 27 patients. The total lethality is 33%, the mean survival
      period is 8 months. Some patients with the unilateral paresis of the left
      recurrent nerve have laryngoesophageal dysfunction with the danger of aspiration
      during swallowing. The shape, position and function of the paretic vocal cord can
      be favourable influenced by the administration of hydrophile gel into the vocal
      cord by the endoscopic route.

PMID- 7526635
TI  - Natural autoantibodies.

PMID- 7526634
TI  - Autoantibody activity and V gene usage by B-cell malignancies.

PMID- 7526633
TI  - Immunogenetic aspects of IgE-mediated responses.
AB  - The reported significant HLA association is consistent with the codominant
      expression of MHC-linked Ir genes. Similar studies are needed in the case of the
      other HLA-immune response associations. It seems unlikely that any unique HLA-D
      genetic sequence will be found only among subjects responding to a particular Ag.
      It is likely, however, that we will find that a particular sequence is a
      necessary, but not sufficient, requirement for responsiveness to a particular
      antigenic epitope. Previous family studies, in which failed to observed parent-to
      child transmission of specific immune responsiveness to a particular allergen,
      suggest that further genetic and/or environmental factors are required for the
      expression of specific immune responsiveness. These factors include variations in
      the degree of antigenic exposure. Of particular importance is the need for Ag
      specific TcR genes to be expressed in the mature T-cell repertoire. In study of
      the specific immune response, there have been several studies of the protein and
      DNA sequences of allergenic proteins; therefore, in regard to understanding the
      genetics of specific immune responsiveness to allergens and its relationship to
      atopic diseases, rapid advances can be anticipated over the next several years.

PMID- 7526636
TI  - Mapping of the polypeptide chain organization of the main extracellular domain of
      the alpha-subunit in membrane-bound acetylcholine receptor by antipeptide
      antibodies spanning the entire domain.
AB  - To study the organization of the polypeptide chain of the main extracellular
      domain of the nicotinic acetylcholine receptor (AChR) alpha-subunit, we examined
      the ability of the native membrane-bound AChR of Torpedo californica (T-AChR) to
      bind a panel of antibodies against overlapping synthetic peptides which
      collectively encompassed this entire domain. Antibodies against the alpha-chain
      peptides alpha 1-16, alpha 89-104 and alpha 158-174 were able to bind to membrane
      bound T-AChR. Other anti-peptide antibodies showed little or no binding to T-AChR
      in the membrane. It is concluded that regions alpha 1-16, alpha 89-104 and alpha
      158-174 are highly exposed on the surface of the alpha subunit of membrane-bound
      AChR.

PMID- 7526637
TI  - The analysis of mast cell function in vivo using mast cell-deficient mice.

PMID- 7526638
TI  - The immunogenetic basis of collagen induced arthritis in mice: an experimental
      model for the rational design of immunomodulatory treatments of rheumatoid
      arthritis.

PMID- 7526639
TI  - Cross-reactions of anti-immunoglobulin sera with synthetic T-cell receptor beta
      peptides: mapping on a 3-dimension model.
AB  - The derived amino acid sequences of human T-cell receptor beta chain shows
      significant homology to lambda light chains of immunoglobulins in its variable,
      joining, and constant regions. We assessed the cross-reactivity between Tcr beta
      chains and immunoglobulin light chains by determining the capacity of rabbit
      antisera to human or murine immunoglobulins to react to a synthesized set of
      nested, overlapping 16-mer peptides corresponding to the VDJC sequence of the Tcr
      beta chain YT35. The observed reactivities were consistent with homologies to
      lambda and kappa light chains, the strongest reactivity being with a peptide that
      corresponds to the "switch peptide" of light chains, as assessed by ELISA binding
      and competitive inhibitions assays. Other regions reactive with anti-light chain
      sera corresponded to CDR1 and Fr3 segments of the variable domain and a segment
      of the constant region predicted to loop out of the tight globular structure. The
      peptide immunochemical results, together with the identification of specific
      regions of sequence correspondence between Tcr beta and the characterized lambda
      light chain Mcg, allowed us to develop a 3-dimensional model of the beta chain
      consistent with its role in antigen recognition.

PMID- 7526640
TI  - The involvement of nitric oxide synthase in the effect of histamine on guinea-pig
      airway smooth muscle in vitro.
AB  - The influence of histamine on nitric oxide synthase (NOS) in the development of
      airway smooth muscle hyperresponsiveness to histamine was investigated in vitro.
      In the absence of histamine, NG-nitro-L-arginine methyl ester (L-NAME, 100
      microM) had no significant effect on the basal tone. However, precontraction of
      the tissues with histamine (0.3 microM) resulted in a significant contractile
      response to L-NAME in the preparations with intact epithelium. Removal of the
      epithelial layer decreased the responses to L-NAME. L-arginine could partially
      reverse the contraction produced by L-NAME. L-NAME enhanced the maximal response
      to histamine, but the sensitivity of the tracheal smooth muscle to histamine was
      not affected. These results suggest that, in the airway, histamine can activate
      NOS, resulting in the release of nitric oxide. The latter may be regarded as a
      local negative modulator to maintain the tissue in a physiological homeostasis.

PMID- 7526641
TI  - No relationship between histamine release measured as metabolite excretion in the
      urine, and serum levels of mast cell specific tryptase in mastocytosis.
AB  - To test the hypothesis that histamine release in mastocytosis patients generally
      occurs without activation of the mast cells, histamine turnover, measured as
      histamine metabolite excretion in the urine, was compared with the serum level of
      mast cell specific tryptase, which is released only during active discharge of
      mast cell granular contents. Twenty mastocytosis patients with a wide range of
      histamine turnover rates were investigated. Slightly increased levels of tryptase
      were found in seven patients with no obvious relationship to histamine metabolite
      excretion. In contrast, there seemed to be a connection between the tryptase
      level and the severity of symptoms. These results strengthen the view that
      histamine in mastocytosis is predominantly released from the mast cells without
      any accompanying active release process. This does not exclude the possibility
      that, in some mastocytosis patients, a limited number of mast cells, or a
      subpopulation, may be actively secreting histamine together with tryptase.

PMID- 7526642
TI  - Possible link between anaphylactoid reactions to anaesthetics and chemicals in
      cosmetics and biocides.
AB  - Binding-inhibition studies involving human IgE antibody to suxamethonium, SUX
      (from a patient with a near-fatal reaction), were performed with five different
      quaternary ammonium compounds (QAC): three common ingredients of cosmetics and
      two commonly used disinfectants, cetrimide and benzalkonium. All the five QAC
      showed immunological cross-reaction with SUX. In addition, at high
      concentrations, they released histamine from basophils of normal subjects. Thus,
      QAC may be both sensitizers and histamine releasers.

PMID- 7526643
TI  - Does the mast cell have an intrinsic role in the pathogenesis of interstitial
      cystitis?
AB  - In order to examine the role of mast cells in the inflammatory bladder disease
      interstitial cystitis, mast cells isolated from the human bladder of normal and
      diseased tissue were challenged with a range of secretagogues. Calcium ionophore
      A23187 and anti-IgE caused histamine release from all bladder mast cells in a
      dose-related manner. Mast cells from the diseased tissue were far more responsive
      than those from the normal tissue. Mast cells from the muscle of normal bladder
      were responsive towards substance P and compound 48/80. However, mast cells from
      interstitial cystitis bladder did not release significant amounts of histamine
      with these two secretagogues.

PMID- 7526644
TI  - Histamine releasing activity of blood mononuclear cells is acquired by means of
      activation of mast cells.
AB  - It has been shown that peripheral blood mononuclear cells (PBMC) obtained from
      atopic patients with acute clinical manifestations of pollinosis, atopic
      dermatitis or bronchial asthma, and preincubated in vitro for 18 hours, acquired
      the ability to induce histamine release from auto-basophils and basophils of
      healthy donors. Both PBMC and their supernatants possessed this histamine
      releasing activity (HRA). During remission, HRA could be reproduced in sensitive
      patients after positive cutaneous tests with a specific allergen. Skin tests with
      non-specific allergen or histamine-induced provocations were ineffective. HRA of
      PBMC was also reproduced in healthy individuals after pronounced Prausnitz
      Kustner reactions or compound 48/80-induced inflammatory responses. It is
      concluded that the in vivo activation of mast cells (MC) might be responsible for
      the acquirement by PBMC of the potential ability to induce histamine release and
      that this ability was realized after in vitro incubation of such prepared PBMC.

PMID- 7526646
TI  - Bacteria-induced IgE-mediated histamine release: examination of patients with
      chronic bronchitis (CB) during acute exacerbations.
AB  - Twelve patients hospitalized with acute exacerbations of chronic bronchitis (CB)
      and infected in the lower respiratory tract with H. influenzae (HI) or
      Streptococcus pneumoniae (SP) were examined. Bacteria, isolated from the
      expectorate caused an IgE-mediated histamine release from the patient's own blood
      leukocytes, indicating that all were sensitized to their own bacteria.
      Sensitization was only observed in some of the patients when tested with a
      standard panel of HI or SP obtained from other patients, indicating the
      importance of using the patient relevant bacterial antigenic determinants. No
      sensitization was found in twelve controls. The patients showed cellular
      hyperreactivity to HI and SP, i.e. the releasability was higher than in the
      control group. The cellular hyperreactivity was not dependent on sensitization
      since it was also found against the non-infecting species. Both sensitization and
      cellular hyperreactivity may contribute to the aggravation of the disease.

PMID- 7526645
TI  - Differential reactivity of human bronchoalveolar lavage mast cells to substance
      P.
AB  - Substance P (SP) stimulates human skin and rodent mast cells. Since neuropeptide
      mediated reflexes may be important in asthma, the ability of SP to stimulate
      human mast cells obtained at bronchoalveolar lavage (BAL) was examined. Routine
      BAL (n = 22) samples were obtained and histamine release experiments performed in
      a standard manner. Spontaneous histamine release was bimodally distributed (Group
      A, high spontaneous release/Group B, normal spontaneous release). Further, Group
      A had significantly elevated corrected SP-induced histamine release compared to
      Group B but the corrected calcium ionophore A23187-induced responses were
      similar. No differences were found in clinical history, age, lavage return or
      total cell numbers between groups. However, differential cell counts revealed
      significantly elevated mast cell numbers in Group A providing further evidence
      for altered mast cell responsivity associated with mast cell hyperplasia. In
      asthma, BAL mast cells have increased spontaneous and stimulated secretory
      responses; thus, in asthma SP may also stimulate pulmonary mast cells.

PMID- 7526647
TI  - Increased numbers of circulating basophils with decreased releasability after
      administration of rhG-CSF to allergic patients.
AB  - Preliminary studies in hematological patients have indicated that treatment with
      rhG-CSF reduces basophil releasability ex vivo. We examined this phenomenon
      further, in allergic patients. Ten patients with grass pollen rhinoconjunctivitis
      were given rhG-CSF (5 micrograms/kg/day s.c.) for 5 days, and examined before and
      after treatment. Basophil counts increased from 5 to 19 x 10(9)/l (P < 0.01).
      Total blood histamine increased from 80 to 160 micrograms/l (P < 0.01),
      corresponding to a decrease in average basophil histamine content from 1.5 to
      0.81 pg/cell (P < 0.01). Isolated mononuclear cells showed a significantly
      decreased histamine release (HR) when stimulated with A23187 and grass. Whole
      blood experiments showed a similar decreased HR to grass and anti-IgE (P < 0.01).
      However, we found an increase in total blood histamine. We conclude that
      treatment with rhG-CSF (1) increases the number of circulating blood basophils,
      (2) reduces the average histamine content per basophil, and (3) reduces the
      basophil releasability. These findings could be due to the mobilization of
      immature basophils from the bone marrow.

PMID- 7526649
TI  - Functional comparison of different histamine-containing IgE-receptor positive
      cells.
AB  - The present study was performed to investigate the histamine-releasing activity
      of non-immunological stimuli on cultured mast cell lines in comparison to
      isolated skin mast cells and basophils as human therapeutic target cells. The
      ionophore A23187 induced a dose dependent histamine release from all cell
      populations (enzymatically isolated human skin mast cells, human peripheral
      basophils and rat basophilic leukemia cells, RBL-1 and RBL-2H3). The lectin
      concanavalin A and the tripeptide formyl-methionyl-leucyl-phenylalanine activated
      only basophils, while the neural mediator substance P and compound 48/80 were
      active only in experiments with skin mast cells. Activators of protein kinase C
      (different phorbol esters and the non-phorbol mezerein) induced direct histamine
      release only from basophils. The data provide further evidence for heterogeneity
      of mast cells and indicate different signal transduction mechanisms following non
      immunological activation.

PMID- 7526648
TI  - Inhibitory effect of interleukin-2 on histamine release from rat mast cells.
AB  - Interleukin-2 (IL-2) inhibited histamine release from rat mast cells induced by
      compound 48/80 in a concentration-dependent manner. The inhibitory effect of IL-2
      on histamine release was also dependent on the length of the incubation period;
      the maximum inhibition was achieved at 8 h after IL-2 addition. Furthermore, IL-2
      inhibited not only IP3 production but also 45Ca uptake in mast cells stimulated
      by compound 48/80. Since IL-2 enhanced [3H]-leucine uptake into mast cells, this
      suggests that protein synthesis may be related in some way with the inhibition of
      histamine release. IL-2 treatment augmented the synthesis of a protein having a
      molecular weight of approximately 35 kDa. From Western blotting analysis, it
      became clear that the production of lipocortin-I was augmented in rat mast cells
      by IL-2 treatment. The present study shows that IL-2 induces the synthesis of
      lipocortin-I in mast cells and that lipocortin-I may play some role in inhibiting
      histamine release from mast cells.

PMID- 7526650
TI  - The role of mast cell activation in cholestatic pruritus.
AB  - Jaundiced patients experience intense pruritus, the pathophysiology of which is
      unclear. In this study, blood histamine concentrations, skin mast cell counts and
      intracellular histamine concentrations in peritoneal mast cells were examined in
      an experimental model of biliary obstruction. Three weeks after bile duct
      ligation (BDL), total blood histamine concentrations were significantly elevated
      compared with those from control animals (p < 0.0001). Skin mast cell counts were
      increased (p < 0.05) and peritoneal mast cell histamine content decreased (p <
      0.05) in jaundiced animals. These results demonstrate that mast cells degranulate
      in biliary obstruction with consequent release of histamine into the systemic
      circulation. This may contribute to cholestatic pruritus. These data may have
      significant pharmacological implications in patients with obstructive jaundice.

PMID- 7526651
TI  - The mechanism of histamine release induced by pilocarpine from different tissues:
      studies on rat peritoneal mast cells.
AB  - Pilocarpine releases histamine from mast cells of cat submandibular gland and rat
      liver. In the salivary gland, histamine is released into the saliva and venous
      outflow. Atropine blocks the salivation, but not histamine release from the
      submandibular gland into the blood. Histamine release from the gland could be due
      to a direct action of pilocarpine on tissue mast cells or to an indirect action
      of mediators (acetylcholine and peptides). These hypotheses were further
      investigated in our present studies on rat peritoneal mast cells. Our results
      show: (1) histamine release from rat peritoneal mast cells induced by pilocarpine
      (ED50 = 1.7 x 10(-2) mol/l) occurs at 1000-fold higher concentrations than by
      substance P (ED50 = 1.7 x 10(-5) mol/l) and in 6.5-fold higher concentrations
      than by atropine (ED50 = 2.6 x 10(-3) mol/l), (2) pilocarpine injected directly
      into the rat peritoneal cavity causes histamine release from peritoneal mast
      cells in 1.8-fold higher concentrations than from isolated rat peritoneal mast
      cells. These results would support the hypothesis that histamine release from cat
      submandibular gland is caused by peptidergic co-transmission during the
      stimulation of the organ.

PMID- 7526652
TI  - Inhibition of histamine secretion from mast cells by lipoxygenase- and
      cyclooxygenase inhibitors.
AB  - We have investigated the effect of inhibitors of lipoxygenase (LOX),
      cyclooxygenase (COX) and dual inhibitors of both enzymes on the degranulation of
      peritoneal rat mast cells (pRMC) activated by different mechanisms. COX
      inhibitors weakly affected histamine secretion induced by A23187 and did not
      influence the histamine secretion induced by protamine in an isotonic medium but
      blocked protamine-induced release in a hypertonic medium. LOX- and dual
      inhibitors inhibited secretion induced by A23187 and protamine under all
      conditions. As A23187 activates pRMC in an isotonic medium by Ca influx, and
      protamine acts in a hypertonic medium by mobilization of intracellular Ca and in
      an isotonic medium by both processes (this paper), LOX but not COX inhibitors,
      may block Ca influx, and both prevent Ca mobilization.

PMID- 7526654
TI  - Mast cells detected in cultures of neonatal rat heart cells.
AB  - Although the presence of mast cells in heart muscle is well documented, their
      possible presence in heart cell cultures has not yet been considered. In this
      paper we show for the first time that cultures from neonatal rat hearts contain
      mast cells in proportions which may exert physiological influences on heart
      muscle cells. Evidence is based on cytochemistry, immunocytochemistry with a
      monoclonal antibody (F2) specific for connective tissue mast cells of the rat,
      and direct estimations of both cellular histamine and histamine released into the
      culture medium. Since the number of nonmuscle cells immunoreactive with antibody
      F2 exceeded the number of cells reacting with conventional cytochemical stains
      for mast cells, a substantial proportion of the former may represent less
      differentiated (precursor) cells.

PMID- 7526653
TI  - Involvement of a serine protease in mast cell activation.
AB  - To examine the putative role of an endogenous serine esterase in mast cell
      activation, we have investigated the effect of inhibitors of, and substrates for,
      alpha-chymotrypsin in normal and permeabilized rat mast cells. These agents
      effectively blocked histamine release induced by anti-IgE, with an enhanced
      potency in permeabilized cells, but were ineffective against secretion evoked by
      compound 48/80. Activation of a chymotryptic enzyme, as evidenced by hydrolysis
      of a fluorescent substrate, was directly demonstrated following immunologic
      stimulation of permeabilized mast cells. No such activation was observed with
      compound 48/80. Immunologic stimulation also led to a significant increase in the
      total chymotryptic activity recoverable from the cells.

PMID- 7526657
TI  - Effect of loop diuretics on rat peritoneal and human lung mast cells.
AB  - The effects of furosemide and bumetanide on immunologically stimulated rat
      peritoneal and human lung mast cells were compared. Furosemide and bumetanide had
      different modulatory actions on the rat peritoneal mast cell. Furosemide
      inhibited anti-IgE-induced histamine release. Preincubation of the cells with the
      drug, prior to anti-IgE stimulation, significantly reduced furosemide's
      inhibitory effect. In contrast, bumetanide potentiated anti-IgE-induced histamine
      secretion from the rat peritoneal mast cell. Both diuretics were modest
      inhibitors of anti-IgE-mediated histamine release from human lung mast cells. For
      furosemide, inhibition decreased with preincubation, while preincubation
      increased bumetanide's inhibitory action.

PMID- 7526656
TI  - Direct effects of second-generation H1-receptor antagonists on the activation of
      human basophils.
AB  - The present study was performed to investigate the putative suppressive effects
      of H1-receptor antagonists (HRA) of the second generation (astemizole (AS),
      cetirizine (CT), loratadine (LO), oxatomide (OX) and terfenadine (TF)) on the
      mediator release from human basophils activated by two classical stimuli. Anti
      IgE-mediated histamine release was inhibited in a dose-dependent fashion by TF
      (maximum inhibitory value: 33.8 +/- 7.6%, 100 microM, n = 7), whereas the other
      HRA exhibited weaker activity. The anti-IgE-induced LTC4 production was strongly
      suppressed by TF, LO and OX (92.4 +/- 6.3%, 90.8 +/- 6.0% and 88.5 +/- 5.6%, 100
      microM, n = 4-5), while AS was less active (56.4 +/- 4.1%, 100 microM, n = 5).
      Histamine release induced by incubation with grass pollen antigen (0.01%) was
      inhibited by TF (40.7 +/- 4.1%, 50 microM, n = 4), but the other HRA showed only
      low activity. The present findings suggest that some HRA might exhibit direct
      inhibitory effects on activation of IgE-receptor bearing cells.

PMID- 7526655
TI  - Role of positive charges of neuropeptide Y fragments in mast cell activation.
AB  - The incubation of neuropeptide Y (NPY) or of NPY C-terminal fragments with rat
      peritoneal mast cells resulted in a dose-dependent histamine secretion (10(-9)
      10(-5) M). A linear correlation between the number of net positive charges of the
      peptides and histamine release potencies was obtained. The histamine secretion
      induced by NPY fragments was inhibited by the treatment of mast cells with
      benzalkonium chloride and pertussis toxin indicating the involvement of G
      proteins.

PMID- 7526660
TI  - Investigations with the selective PKC inhibitor chelerythrine on human basophils.
AB  - Modulation of protein kinase C (PKC) activity in basophils (B) can influence IgE
      mediated histamine release (HR). The present study investigated the effects of
      chelerythrine, which inhibits isolated PKC (IC50 0.7 microM), on different
      activation pathways in B. Fc epsilon RI-mediated HR was strongly inhibited by
      chelerythrine (86.5 +/- 5.4%, 5 microM, n = 11). TPA-induced mediator release was
      also suppressed: 77.1 +/- 8.5% inhibition (7.5 microM). HR due to non
      immunological stimuli (A23187, FMLP) was strongly inhibited by chelerythrine.
      Previously, other selective PKC-inhibitors have been shown to potentiate IgE
      mediated HR from B suggesting a negative modulatory role of PKC, whereas non
      specific inhibitors such as staurosporine inhibited HR. Chelerythrine might
      therefore be less selective for PKC. This may be indicated by the fact that
      chelerythrine inhibits PKC at its catalytic domain, which is homologous with
      other protein kinases.

PMID- 7526659
TI  - Lateral movement of mast cell surface protein detected by gold-labeled anti-IgE
      and its relation with fodrin.
AB  - Rat mast cells were incubated with gold-conjugated concanavalin A and the
      movement of gold particles was observed using a polarization microscope. In
      resting cells, the movement of gold particles was very slow. When cells were
      stimulated with compound 48/80, the gold particles rapidly moved laterally,
      unrelated to granule extrusion. When sensitized mast cells were stimulated with
      gold-conjugated anti-IgE (anti-IgE-gold), patching of anti-IgE-gold was also
      observed. Immunofluorescence microscopy of rat mast cells stained with anti
      fodrin antibody and rhodamine-phalloidin revealed that both fodrin and actin
      exist beneath the cell membrane forming a complicated network. After stimulation
      of the cells with anti-IgE-gold, the fodrin network was disrupted and thin
      fluorescence was observed homogeneously on the cell surface. By means of Western
      blotting, alpha-fodrin was detected in the membrane fraction of mast cells at the
      240 kDa protein band. From the present study, it is suggested that disruption of
      the fodrin network may occur in association with the process leading to mast cell
      degranulation.

PMID- 7526658
TI  - Immunohistochemical studies with skin mast cells.
AB  - Using different histochemical and immunohistochemical methods we demonstrate that
      isolated skin mast cells used for different pharmacological and biochemical
      studies exhibit the same staining pattern compared to skin mast cells in situ.
      Surface structures and enzyme content of the cells appear not to be influenced by
      the isolation technique. We also observed no differences in the staining pattern
      of mast cells in neurofibroma, a cutaneous disorder characterized by an increase
      of mast cell numbers.

PMID- 7526661
TI  - Mechanism and function of histamine-sodium cotransport by astroglial cells.
AB  - There is a saturable and high affinity uptake system for histamine in astroglial
      cells. The uptake is metabolically driven, sodium dependent and electrogenic. We
      consider the functional significance of these findings.

PMID- 7526662
TI  - H3 autoreceptors and muscarinic acetylcholine receptors modulate histamine
      release in the anterior hypothalamus of freely moving rats.
AB  - To investigate the modulation of histamine release by autoreceptors and
      heteroreceptors, the rat anterior hypothalamus was superfused through a push-pull
      cannula with agonists or antagonists of histamine and acetylcholine muscarinic
      receptors. Superfusion with the H3 receptor agonist (R)-alpha-methylhistamine
      inhibited, while superfusion with thioperamide (H3 antagonist) enhanced histamine
      release. Superfusion with carbachol (a mixed M1, M2, M3 agonist) inhibited the
      release of histamine. The release of endogenous histamine was enhanced on
      superfusion with atropine (a mixed M1, M2, M3 antagonist). The M3 muscarinic
      antagonist 4-diphenylacetoxy-N-methylpiperidine enhanced the release rate of
      histamine. It is concluded that in the anterior hypothalamus the release of
      endogenous histamine is modulated by H3 autoreceptors. Moreover, acetylcholine
      released from cholinergic neurons also modulates the release of histamine via M1
      and/or M3 heteroreceptors.

PMID- 7526663
TI  - Time course of the effects of histamine, thioperamide and EEDQ on H3 receptors in
      the mouse brain.
AB  - The effects of histamine, thioperamide and EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline) at the noradrenaline release-modulating H3 receptor in the
      mouse brain were examined. In superfused mouse brain cortex slices preincubated
      with 3H-noradrenaline, the inhibitory effect of histamine on the electrically
      (0.3 Hz) evoked tritium overflow was virtually identical when the time of
      exposure was 30, 80 or 130 min; after withdrawal of histamine, the evoked
      overflow recovered within 80 min. The attenuation of the effect of histamine by
      thioperamide was reversible within 50 min after withdrawal of the antagonist,
      whereas the attenuation produced by EEDQ remained constant for at least 80 min.
      In conclusion, the effects of histamine and thioperamide at the H3 receptor are
      readily reversible, whereas EEDQ appears to be an irreversible antagonist;
      desensitization of the H3 receptor does not occur.

PMID- 7526664
TI  - Effect of isolation stress on brain mast cells and brain histamine levels in
      rats.
AB  - The effects of the chronic social stress of isolation on changes in brain mast
      cells (MC), the hypothalamic histamine content and the activity of the
      hypothalamic-pituitary adrenal (HPA) axis were investigated in rats. Social
      stress of isolation markedly reduced the total number of brain mast cells, most
      significantly by 90% in the first day. The extent of MC degranulation, 36-67%, in
      stressed rats did not significantly differ from that in control animals, 45-58%.
      Isolation stress substantially, though not significantly, increased the
      hypothalamic histamine content. The serum corticosterone levels in isolated rats
      did not significantly differ from the control levels. These results indicate that
      social stress of isolation considerably diminishes the number of brain MC and
      suggest that histamine which might be liberated from these cells does not
      significantly influence the HPA activity.

PMID- 7526665
TI  - Nitric oxide modulates cardiac and mast cell anaphylaxis.
AB  - Anaphylaxis in the isolated guinea-pig heart was associated with a sudden release
      of histamine with a long-lasting release of nitrite (NO2-), an oxidation product
      of NO. NG-monomethyl-L-arginine (MeArg, 300 microM) increased the severity of
      cardiac anaphylaxis, as shown by the decrease in the coronary flow and by a
      prolonged duration of antigen-induced arrhythmias. Concomitantly, MeArg increased
      the release of histamine while decreasing the release of nitrite. Sodium
      nitroprusside (NaNP, 10(-5)-10(-4) M) reduced the severity of cardiac anaphylaxis
      by increasing coronary flow and shortening the duration of antigen-induced
      arrhythmias. Concomitantly, NaNP decreased the release of histamine while
      increasing the release of nitrite. In mast cells isolated from actively
      sensitized guinea-pigs, the release of histamine elicited by specific antigen was
      increased by MeArg and decreased by NaNP. In conclusion, endogenous and exogenous
      NO antagonizes the effect of vasoconstrictor mediators released after antigen
      challenge and plays a protective role in anaphylactic reactions "in vitro".

PMID- 7526666
TI  - Gastric acid and histamine secretion in patients on continuous ambulatory
      peritoneal dialysis (CAPD).
AB  - Gastric secretion was measured in patients with chronic renal failure (CRF) on
      continuous ambulatory peritoneal dialysis (CAPD), non-uraemic patients with a
      duodenal ulcer (DU), and healthy volunteers (HV). Basal acid outputs were not
      significantly different in the three groups. Under pentagastrin stimulation, acid
      secretion was lower in CAPD patients than in DU patients (p < 0.02) but not
      different from HV controls. Between CAPD and DU, basal histamine secretion
      measured in the gastric juice was not different, but the concentration in blood
      plasma was significantly lower in the CAPD group (p < 0.05). Under pentagastrin
      stimulation, gastric histamine output and plasma histamine concentration were
      significantly lower in CAPD patients (p < 0.05, respectively). Both basal and
      pentagastrin-stimulated gastric acid and histamine outputs were directly related.
      These results suggest that CAPD patients do not have an increased risk of
      developing DU, but may need acid blockade if they are treated for
      hyperphosphataemia with aluminium containing drugs.

PMID- 7526667
TI  - Macrophages and lymphocytes: alternative sources of histamine.
AB  - Some recent observations have indicated that cells other than mast cells, notably
      macrophages, may contain significant amounts of histamine. Using a histamine
      specific radioimmunoassay, we found that human blood monocytes and lymphocytes
      contain about 0.05 pg histamine/cell. Various other cells, e.g. fibroblasts,
      colorectal tumor, kidney and ovarian cells, and murine bone marrow derived
      macrophages contained markedly less histamine (< 0.008 pg/cell). Ionophore A23187
      (1 microM) released up to 50% of the total histamine from monocytes and
      lymphocytes. C5a caused a dose-dependent histamine release of up to 40% in
      monocytes and up to 20% in lymphocytes. Substance P induced a release only in
      cells of certain donors. Lipopolysaccharide, concanavalin A, and compound 48/80
      had no effect. Culturing of the cells caused a loss of cellular histamine and its
      releasability. In view of the huge numbers of monocytes and lymphocytes in the
      blood, the histamine in these cells has to be taken into account under both
      physiological and pathophysiological conditions.

PMID- 7526668
TI  - [Experimental choroidal neovascularization in the rat].
AB  - We successfully produced, highly (78%) reproducible experimental choroidal
      neovascularization (ChNV) in the subretinal space of pigmented rats with intense
      diode laser photocoagulation. ChNV in the pigmented rat was characterized by
      rapid development of neovascular membrane and proliferation of retinal pigment
      epithelium in the subretinal space. This procedure may be useful as an
      experimental model for ChNV.

PMID- 7526669
TI  - [Role of the prostatic capsule in the physiopathology of benign prostatic
      hypertrophy].

PMID- 7526670
TI  - Porcine mitogen-induced interferon.
AB  - Induction of porcine interferon (PoIFN) with different lectins
      (phytohaemagglutinin, Lens culinaris lectin, Arachis hypogea lectin) in various
      concentrations (500, 50 and 5 micrograms/ml) was studied. Kinetics of PoIFN
      appearance was analyzed by antiviral and antiproliferative tests in human
      transformed and nontransformed cells. The relation between antiviral and
      antiproliferative activity of PoIFN in terms of respective units was determined.
      PoIFN was characterized in comparison with human interferon alpha by the
      acidostability and thermostability tests.

PMID- 7526671
TI  - Subcortical low intensity in early cortical ischemia.
AB  - PURPOSE: To describe subcortical low intensity on T2- and proton density-weighted
      MR images in early cortical ischemia and to discuss a cause of these findings.
      METHODS: Nine patients with early cortical ischemia were studied with proton
      density- and T2-weighted images, and T1-weighted images at 1.5 T. Gadolinium
      enhancement was added in six cases. RESULTS: In all cases there was high to
      intermediate intensity in the cortex and low intensity in the subcortical white
      matter (subcortex) on the proton density- and T2-weighted images. No significant
      signal abnormalities were shown on T1-weighted images in the subcortex; gyriform
      enhancement was seen in the affected cortex in all of the six patients studied
      with gadolinium. Of the four patients with follow-up MRs, the subcortical low
      intensity changed to high intensity in two and remained low in two patients in
      the chronic stage. Neither hemorrhage nor calcification was seen on CT.
      CONCLUSION: Iron accumulation in the subcortex caused by disruption of the axonal
      transportation and continuous production of free radicals caused by the hypoxic
      ischemic state most likely reduces the signal intensity of the subcortex on the
      proton density- and T2-weighted images. The subcortical low intensity on the
      proton density- and T2-weighted images is an important diagnostic sign of early
      cortical ischemia.

PMID- 7526672
TI  - [Allergy to muscle relaxants].

PMID- 7526674
TI  - Treatment of the common cold in children.

PMID- 7526673
TI  - Diagnosis of IgE mediated allergy in clinical practise.
AB  - The basis of an allergy diagnosis is the patient's case history. In patients with
      inhalant allergy, an accurate diagnosis is often received when the case history
      is supported by the result of skin prick test (SPT) or in vitro-test for allergen
      specific IgE. IgE screening tests should, in cost-effective clinical routines,
      preferably be used in patients with a doubtful allergy history, in order to find
      out which patients do not require allergen specific testing. Determination of
      allergen specific IgE in the serum could be used when there is suspicion of
      allergy against only one or a few allergens, whereas SPT should be used when
      testing with many allergens is necessary. In patients with suspicion of allergy
      against food stuffs or drugs, test methods are of more limited value than in
      inhalant allergy and double blind placebo controlled challenge tests often have
      to be performed in order to get a definitive diagnosis. In insect venom allergy,
      the history should be supplemented with SPT and determination of venom specific
      IgE before starting desensitisation therapy.

PMID- 7526675
TI  - Effects of amiodarone, sematilide, and sotalol on QT dispersion.
AB  - To study the effects of class III agents on QT/QTc dispersion in patients with
      heart disease and cardiac arrhythmias, QT dispersion and QRS and RR intervals
      were compared in patients before and after treatment with amiodarone (n = 26),
      sematilide (n = 26), and sotalol (n = 26). QT, QRS, and RR intervals, and QTc
      values were calculated for each complex, and their mean values were calculated
      for each lead. QT and QTc dispersions were defined as differences between the
      minimal and maximal QT or QTc values in each of the 12 leads studied. Amiodarone,
      sematilide, and sotalol all significantly prolonged the QT interval and the QTc
      value. Significant reductions in QT and QTc dispersions were only found in the
      amiodarone group (QT dispersions: 79 +/- 13 vs 49 +/- 14 ms; p < 0.001; QTc
      dispersions: 0.08 +/- 0.02 vs 0.05 +/- 0.01 s1/2; p < 0.001). The mean RR
      interval was significantly increased in patients after treatment with amiodarone
      (p < 0.001) and sotalol (p < 0.001), but not in patients receiving sematilide
      treatment (p > 0.2). The baseline QT and QTc dispersions were significantly
      greater in patients with than without myocardial infarction before treatment (p <
      0.001). The mean baseline values for QT/QTc dispersions were not significantly
      different among all 3 groups. However, only amiodarone significantly reduced the
      QT dispersion (from 76 +/- 10 to 46 +/- 11 ms; p < 0.001) and QTc dispersion
      (from 0.09 +/- 0.02 to 0.05 +/- 0.01 s1/2; p < 0.001) in patients with myocardial
      infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526676
TI  - Alterations in nitric oxide synthase activity, superoxide anion generation, and
      platelet aggregation in systemic hypertension, and effects of celiprolol.
AB  - A decrease in endothelium-derived relaxing factor or nitric oxide has been
      proposed as a potential mechanism of increased vascular resistance in
      hypertension. An increase in the generation of superoxide anions, which degrade
      nitric oxide and induce platelet aggregation, may also compromise regional blood
      flow in hypertension. Recent studies show that human neutrophils generate nitric
      oxide, which has a similar biologic profile to the endothelium-derived relaxing
      factor. This study measured nitric oxide synthase activity and superoxide
      generation in human neutrophils and platelet aggregation in patients with
      essential hypertension. Nitric oxide synthase activity, measured as conversion of
      3H-L-arginine to 3H-L-citrulline, in peripheral blood neutrophils was decreased
      in hypertensive subjects (percent conversion of 3H-L-arginine: 4.2 +/- 0.5 vs 9.0
      +/- 3.0 in control subjects; p < 0.01). Neutrophil superoxide anion generation,
      measured as conversion of ferricytochrome C to ferrocytochrome C, in response to
      phorbol-12-myristate 13-acetate (100 ng/ml) was higher in hypertensive subjects
      (17.5 +/- 8.1 vs 13.2 +/- 3.0 nmoles/10(6) cells/10 minutes in control subjects;
      p < 0.05). Patients were treated with a selective beta blocker, celiprolol, for 8
      weeks. Supine blood pressure decreased from 177/103 mm Hg (mean +/- SD 18/7) to
      160/92 mm Hg (mean +/- 10/5; p < 0.02), while heart rate was unchanged (73 +/- 11
      vs 69 +/- 10 beats/min). Epinphrine and adenosine diphosphate-induced platelet
      aggregation was also increased in hypertensive subjects.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7526677
TI  - Variability of the ventricular response in atrial fibrillation and prognosis in
      chronic nonischemic mitral regurgitation.
AB  - Although reduced heart rate (HR) variability during sinus rhythm is associated
      with an adverse prognosis in a variety of clinical settings, the significance of
      measures of variability of the ventricular response in atrial fibrillation (AF)
      requires clarification. AF is common among patients with chronic severe mitral
      regurgitation (MR) and potentially limits the application of HR variability
      techniques in this population. Therefore, this study examined the physiologic
      correlates and prognostic significance of measures of HR variability in 21
      patients with nonischemic causes of chronic severe MR who had chronic AF and
      underwent 24-hour ambulatory electrocardiography as part of a prospective study
      of the natural history of regurgitant valvular heart disease. Patients were
      followed for up to 9.1 years and end points of mortality and progression to
      mitral valve surgery were tabulated. Time- and frequency-domain measurements of
      high-, low-, and ultra-low-frequency HR variability were computed and compared
      with resting ventricular function by radionuclide cineangiography and outcome.
      All measures of HR variability were covariate (pair-wise r values between 0.48
      and 0.99, all p values < 0.03), and none of the variables was significantly
      related to age, ventricular premature complex (VPC) density, or right or left
      ventricular ejection fraction. Reductions in time-domain measurements of ultra
      low- and high-frequency HR variability were significant predictors of the
      combined risk of mortality or requirement for mitral valve surgery (p = 0.02 and
      p = 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526678
TI  - Neutropenia occurring during treatment with vesnarinone (OPC-8212).

PMID- 7526679
TI  - Clinical significance of abnormal prothrombin (DCP) in relation to postoperative
      survival and prognosis in patients with hepatocellular carcinoma.
AB  - OBJECTIVES: In this study we correlate plasma des-gamma-carboxy prothrombin (DCP)
      levels with prognosis in patients with hepatocellular carcinoma (HCC) in
      combination with serum alpha-fetoprotein levels (AFP). METHODS: Levels of DCP
      were measured in 165 patients with HCC by an enzyme immunoassay (EIA, E-1023)
      with an anti-DCP monoclonal antibody. RESULTS: There was no correlation between
      the plasma DCP levels and the serum AFP levels. The positive rate obtained from
      the combination assay was 72.1%. The survival rates of the patients with elevated
      levels of both DCP and AFP were significantly lower than those of the groups with
      normal DCP and AFP levels (p < 0.05). The disease-free survival rates of patients
      with elevated DCP and AFP levels were also significantly lower than those of
      patients with normal DCP and AFP levels (p < 0.05). The recurrence rate within a
      postoperative period of 2 yr was higher in the patients with elevated DCP and AFP
      levels than in those with normal levels. CONCLUSIONS: The determination of plasma
      DCP levels combined with AFP levels appears to be useful for the diagnosis and
      prognosis of HCC, and is useful also in postoperative monitoring for recurrence.

PMID- 7526681
TI  - A four base pair deletion 5' to the A gamma T gene is associated not only with
      decreased expression of the A gamma T-globin gene, but also of the G gamma-globin
      gene in cis.
AB  - A four base pair deletion 5' to A gamma T-globin gene at positions -222 to -225
      has been reported to reduce the expression of this gene. To evaluate the
      prevalence and effect of this deletion, PCR-based methods were employed. The
      deletion had a gene frequency of 0.06 in a sample of African-American individuals
      with sickle cell trait, 0.18 in adult African-Americans with normal Hb AA, and
      0.36 in caucasians. Seventy cord blood samples from African-American newborns
      with Hb AA were evaluated by both HPLC and PCR. The frequency of the A gamma T
      allele was 0.13. The A gamma T-globin chain was always present in a lower
      proportion than the A gamma I allele (70% of A gamma I), but the percentage of A
      gamma-globin was the same whether or not A gamma T was present. The total
      percentage of Hb F, however, was significantly lower in the group with the A
      gamma T allele (77.1% vs. 87.4%, P < 0.01). These results indicate that the four
      base pair deletion is not only associated with reduced expression of the A gamma
      T allele, but also of the G gamma allele in cis, further suggesting a possible
      role of this region in the modulation of the expression of the linked gamma
      globin genes.

PMID- 7526682
TI  - Effect of stem cell factor (c-kit ligand) on clonogenic leukemic precursor cells:
      synergy with other hematopoietic growth factors.
AB  - Using clonogenic assay we investigated the effect of stem cell factor (SCF) on
      the in vitro growth of clonogenic precursor cells from acute myeloid leukemia
      (AML) and myelodysplastic syndromes (MDS) in the presence or absence of
      recombinant human erythropoietin (rhEpo) or recombinant human granulocyte colony
      stimulating factor (rhG-CSF). SCF as a single factor did not induce significant
      colony formation, and even in the presence of rhEPO or rhG-CSF it very weakly
      stimulated erythroid colony formation and was rarely capable of inducing myeloid
      colony formation by clonogenic leukemic cells. In culture dishes supplemented
      with SCF, both myeloid and erythroid colony formations were dramatically enhanced
      in MDS, regarding both colony number and size. Colony-formation abilities by MDS
      progenitors were improved following costimulation with SCF and rhEpo. These
      results suggest that SCF may have a therapeutic role in restoring hematopoiesis
      in patients with MDS.

PMID- 7526683
TI  - Erythema nodosum caused by the administration of granulocyte colony-stimulating
      factor in a patient with refractory anemia.

PMID- 7526684
TI  - Use of colony-stimulating factors for the treatment of carbimazole-induced
      agranulocytosis.

PMID- 7526686
TI  - Danaparoid is not a low-molecular-weight heparin.

PMID- 7526680
TI  - High expression of CD56 (N-CAM) in a patient with cutaneous CD4-positive
      lymphoma.
AB  - Cutaneous lymphoma is a disease characterized with massive skin infiltration of
      lymphoid malignant cells. They commonly express some T-cell markers, such as CD2,
      CD3, CD4, and CD7, and thus termed as CTCL (cutaneous T cell lymphoma). Here, we
      present a case with CD56/N-CAM-positive cutaneous lymphoma, which appears
      lymphocytic morphology and expresses CD4, but does not express CD2, CD3, CD8,
      CD14, CD16, CD57, and CD20. The most malignant cells contained no distinctive
      azurophilic granules in the cytoplasm. Southern blot analysis revealed that T
      cell receptor-beta, gamma, and immunoglobulin heavy chain genes in the cells were
      in germ-line configurations. Electron microscopic examination showed
      characteristics of lymphoid cells with higher nucleocytoplasmic ratio and lacked
      structures typical of other cell types (i.e., epithelial cells, neuroendocrine
      cells, and mesenchymal cells). Thus, the cells are likely to be immature lymphoid
      cells. Histological analysis revealed the cells infiltrate mainly into the dermis
      with angiocentric growth pattern. The clinical course was aggressive, with rapid
      involvement of bone marrow and central nervous system. These striking features of
      the patient may represent a novel fraction (CD2-, CD4+, and CD56+) of cutaneous
      lymphoma.

PMID- 7526685
TI  - Independent origins of cystic fibrosis mutations R334W, R347P, R1162X, and 3849 +
      10kbC-->T provide evidence of mutation recurrence in the CFTR gene.
AB  - Microsatellite analysis of chromosomes carrying particular cystic fibrosis
      mutations has shown different haplotypes in four cases: R334W, R347P, R1162X, and
      3849 + 10kbC-->T. To investigate the possibility of recurrence of these
      mutations, analysis of intra- and extragenic markers flanking these mutations has
      been performed. Recurrence is the most plausible explanation, as it becomes
      necessary to postulate either double recombinations or single recombinations in
      conjunction with slippage at one or more microsatellite loci, to explain the
      combination of mutations and microsatellites if the mutations arose only once.
      Also in support of recurrence, mutations R334W, R347P, R1162X, and 3849 + 10kbC-
      >T involve CpG dinucleotides, which are known to have an increased mutation rate.
      Although only 15.7% of point mutations in the coding sequence of CFTR have
      occurred at CpG dinucleotides, approximately half of these CpG sites have mutated
      at least once. Specific nucleotide positions of the coding region of CFTR,
      distinct from CpG sequences, also seem to have a higher mutation rate, and so it
      is possible that the mutations observed are recurrent. G-->A transitions are the
      most common change found in those positions involved in more than one mutational
      event in CFTR.

PMID- 7526687
TI  - Sickle cell anemia and fetal hemoglobin.
AB  - Fetal hemoglobin, the predominant hemoglobin of the fetus, is good for sickle
      cell anemia. This hemoglobin inhibits the polymerization of sickle hemoglobin.
      Clinical studies have shown that at any level of fetal hemoglobin, the more that
      is present, the better off is the patient. We are now able to increase fetal
      hemoglobin levels by pharmacologic means. We should know shortly if this is
      associated with clinical benefit.

PMID- 7526689
TI  - FK506 treatment of noninfectious uveitis.
AB  - PURPOSE: We studied the clinical effects of the immunosuppressive agent FK506 in
      patients with noninfectious uveitis. METHODS: This study was designed as a
      multicenter open clinical trial in Japan. Sixteen patients with noninfectious
      uveitis who had visited the Uveitis Survey Clinic of the Yokohama City University
      Hospital were given FK506. Eight had Behcet's disease; five, Vogt-Koyanagi-Harada
      syndrome; one, sympathetic ophthalmia; one, retinal vasculitis; and one,
      sarcoidosis. In patients with Behcet's disease, ocular attack score before and
      after therapy was compared to judge clinical status. For the other diseases, the
      ocular inflammatory symptoms were observed after the initiation of FK506
      treatment. All patients underwent blood and urine examinations,
      electrocardiography, and chest x-rays before and after FK506 treatment. RESULTS:
      Of the patients with Behcet's disease, five improved, one remained unchanged, one
      deteriorated, and the status of one could not be determined. Of the patients with
      Vogt-Koyanagi-Harada syndrome, four improved, and one remained unchanged. The
      patient with sympathetic ophthalmia improved, the patient with retinal vasculitis
      remained unchanged, and the status of the patient with sarcoidosis could not be
      determined. Major adverse effects were sensations of warmth, hypomagnesemia,
      renal dysfunction, glucose intolerance, nausea, vomiting, and disorders of the
      central nervous system. All adverse effects disappeared or improved when FK506
      was stopped or when the dosage was decreased. Renal dysfunction and glucose
      intolerance appeared when the blood level of FK506 was high. CONCLUSIONS: FK506
      was effective in patients with uveitis, but it is important to monitor the
      occurrence of adverse effects.

PMID- 7526688
TI  - The effects of labor on maternal and fetal levels of insulin-like growth factor
      binding protein-1.
AB  - OBJECTIVE: Our purpose was to determine the effects of labor and fetal hypoxia on
      the levels of insulin-like growth factor binding protein-1 in the maternal and
      fetal circulation. STUDY DESIGN: Serum levels of insulin-like growth factor
      binding protein-1 were determined in maternal and umbilical blood at delivery in
      two groups. The first group included 43 vaginal deliveries and 23 elective
      cesarean sections. The second group consisted of 44 women; in 24 the liquor was
      meconium stained and in 20 it was clear. RESULTS: Levels of insulin-like growth
      factor binding protein-1 in the neonate were lower in deliveries occurring before
      onset of labor (p < 0.001), Mann-Whitney U test) and higher in cases with severe
      meconium staining (p = 0.01). There were no differences in maternal levels of
      insulin-like growth factor binding protein-1 between subjects in labor and not in
      labor or those with or without meconium staining. CONCLUSION: The process of
      labor leads to an increase in fetal levels of insulin-like growth factor binding
      protein-1. This increase may well be associated with the relative fetal stress
      that occurs during labor. This suggestion is supported by the finding of the
      highest levels in labors in which there was thick staining of the liquor.

PMID- 7526690
TI  - Current practice among NeuroDevelopmental Treatment Association members.
AB  - OBJECTIVES: The purposes of this study were (a) to describe how
      neurodevelopmental treatment (NDT) is currently being provided by occupational
      therapists, physical therapists, and speech-language therapists (e.g., setting,
      duration, frequency, techniques used), (b) to determine which populations are
      viewed by clinicians as most responsive to NDT intervention, and (c) to examine
      clinicians' attitudes and beliefs regarding NDT philosophy, role delineation, and
      provision of NDT service. METHOD: A sample of 431 members of the Neuro
      Developmental Treatment Association, Inc. responded to a questionnaire examining
      current practice in NDT. RESULTS: Respondents typically provided NDT once or
      twice a week with an emphasis on qualitative movement and functional performance.
      Persons with mild to moderate levels of motor dysfunction were viewed as
      responding best to NDT. Therapists reported using an eclectic approach that
      combines NDT with other treatment approaches. The three disciplines reported
      using different types of NDT handling techniques to accomplish discipline
      specific goals. There was a strong belief that NDT is a total management program
      that considers the client's functioning in many settings and that families should
      be involved in the client's therapy program. CONCLUSION: There was wide consensus
      that the theoretical tenets underlying NDT need revision to consider current
      theoretical thinking and practice.

PMID- 7526691
TI  - Vascular endothelial growth factor, platelet-derived growth factor, and insulin
      like growth factor-1 promote rat aortic angiogenesis in vitro.
AB  - The purpose of this study was to evaluate the vasoformative response of isolated
      vascular explants to a variety of growth factors that have been shown to
      stimulate angiogenesis. Rings of rat aorta were cultured in collagen gels under
      serum-free conditions in the presence or absence of vascular endothelial growth
      factor (VEGF), natural platelet-derived growth factor (PDGF), PDGF-AA, PDGF-BB,
      insulin-like growth factor-1 (IGF-1), transforming growth factor-alpha (TGF
      alpha), transforming growth factor-beta 1 (TGF-beta 1), epidermal growth factor
      (EGF), interleukin-1 alpha (IL-1 alpha), or hepatocyte growth factor (HGF). The
      angiogenic response of the rat aorta was stimulated by VEGF, PDGF, PDGF-AA, PDGF
      BB, and IGF-1. Maximum stimulatory effects were obtained with VEGF and PDGF-BB.
      By contrast, TGF-beta 1 and IL-1 alpha had inhibitory activity. No significant
      effects were observed with TGF-alpha, EGF, or HGF. The vascular outgrowth of VEGF
      stimulated cultures was primarily composed of microvessels, whereas that of PDGF-
      and IGF-1-stimulated cultures contained an increased number of fibroblast-like
      cells. The inability of TGF-alpha, TGF-beta 1, IL-1 alpha, EGF, and HGF to
      stimulate rat aortic angiogenesis in serum-free culture suggests that either
      these factors require the mediatory activity of accessory cells that are not
      present in the rat aorta model or that blood vessels are heterogeneous in their
      capacity to respond to different angiogenic factors.

PMID- 7526693
TI  - Mallory body filaments become insoluble after normal assembly into intermediate
      filaments.
AB  - The deposition of 8-to-10-nm filaments into inclusion bodies is a fundamental
      cellular change that occurs in several degenerative processes of many tissues.
      However, little is known about the pathological filaments including whether the
      filaments assemble by the same mechanisms that govern the assembly of normal
      intermediate filaments. We have addressed this issue by studying the in vitro
      reassembly of the cytokeratin filaments that are deposited into experimental
      murine Mallory bodies (MBs) but have not yet become covalently crosslinked
      components of the MB. The reassembly process of both normal hepatocellular and MB
      derived cytokeratins (CKs) was similar and characterized by a hierarchy of
      protofilament and protofibrils with a prominent axial periodicity of
      approximately 21 nm (normal hepatocellular CK, 20.7 +/- 2 nm; MB-derived CK, 20.1
      +/- 2 nm). Purified MB-derived CK and normal hepatocellular CK comigrated in
      polyacrylamide gel electrophoresis indicating composition by similar CK isoforms.
      These results indicate that intermediate filaments formed from MB-derived CK are
      indistinguishable from filaments assembled from normal CK. On this basis, we
      conclude that the intermediate filaments that form inclusion bodies are not
      aberrantly assembled but become aggregated and post-translationally modified
      after their initial formation.

PMID- 7526695
TI  - Agonist-induced redistribution of calponin in contractile vascular smooth muscle
      cells.
AB  - Calponin is a thin filament-associated protein that has been implicated in
      playing an auxiliary regulatory role in smooth muscle contraction. We have used
      immunofluorescence and digital imaging microscopy to determine the cellular
      distribution of calponin in single cells freshly isolated from the ferret portal
      vein. In resting cells calponin is distributed throughout the cytosol, associated
      with filamentous structures, and is excluded from the nuclear area of the cell.
      The ratio of surface cortex-associated calponin to cytosol-associated calponin
      (R) was found to be 0.639 +/- 0.021. Upon depolarization of the cell with
      physiological saline solution containing 96 mM K+, the distribution of calponin
      did not change from that of a resting cell (R = 0.678 +/- 0.025, P = 0.369). Upon
      stimulation with an agonist (10 microM phenylephrine) that is known to activate
      protein kinase C (PKC) in these cells, the cellular distribution of calponin
      changed from primarily cytosolic to primarily surface cortex associated (R = 1.24
      +/- 0.085, P < 0.001). This agonist-induced redistribution of calponin was
      partially inhibited by the PKC inhibitor calphostin, overlapped in time with PKC
      translocation, and preceded contraction of these cells. These results suggest
      that the physiological function of calponin may be to mediate agonist-activated
      contraction via a PKC-dependent pathway.

PMID- 7526694
TI  - The volume-sensitive organic osmolyte-anion channel VSOAC is regulated by
      nonhydrolytic ATP binding.
AB  - Efflux of intracellular organic osmolytes to the external medium is a ubiquitous
      response to cell swelling. Accumulating evidence indicates that volume regulatory
      loss of structurally unrelated organic osmolytes from cells is mediated by a
      relatively nonselective volume-sensitive anion channel. In C6 cells, we have
      termed this channel VSOAC for volume-sensitive organic osmolyte-anion channel.
      Swelling-induced activation of VSOAC required the presence of ATP or
      nonhydrolyzable ATP analogues [adenosine 5'-O-(3-thiotriphosphate),
      adenylylmethyl-enediphosphonate (AMP-PCP), or 5'-adenylylimidodiphosphate] in the
      patch pipette. Sustained activation of VSOAC also required ATP. Channel rundown
      was observed when cellular ATP levels were lowered by intracellular dialysis with
      the patch pipette solution. Rundown was prevented by the ATP analogue AMP-PCP.
      Passive swelling-induced myo-[3H]inositol and [3H]taurine efflux was blocked by
      metabolic inhibitors that decreased cellular ATP levels. Titration of cellular
      ATP levels with azide demonstrated that the apparent dissociation constant (Kd)
      for ATP of both myo-inositol and taurine efflux was approximately 1.7 mM. The
      high Kd for ATP indicates that cellular metabolic state plays an important role
      in modulating organic osmolyte loss. Regulation of VSOAC activity by ATP prevents
      depletion of metabolically expensive organic osmolytes when cellular energy
      production is reduced. In addition, ATP-dependent regulation provides essential
      feedback to minimize the loss of energy-producing carbon sources such as
      pyruvate, short-chain fatty acids, ketone bodies, and amino acids, which readily
      permeate this channel.

PMID- 7526692
TI  - An immunohistochemical study of the pathology of fatal malaria. Evidence for
      widespread endothelial activation and a potential role for intercellular adhesion
      molecule-1 in cerebral sequestration.
AB  - The sequestration of parasitized erythrocytes in the microvasculature of vital
      organs is central to the pathogenesis of severe Plasmodium falciparum malaria.
      This process is mediated by specific interactions between parasite adherence
      ligands and host receptors on vascular endothelium such as intercellular adhesion
      molecule-1 (ICAM-1) and CD36. Using immunohistochemistry we have examined the
      distribution of putative sequestration receptors in different organs from fatal
      cases of P. falciparum malaria and noninfected controls. Receptor expression and
      parasite sequestration in the brain were quantified and correlated. Fatal malaria
      was associated with widespread induction of endothelial activation markers, with
      significantly higher levels of ICAM-1 and E-selectin expression on vessels in the
      brain. In contrast, cerebral endothelial CD36 and thrombospondin staining were
      sparse, with no evidence for increased expression in malaria. There was highly
      significant co-localization of sequestration with the expression of ICAM-1, CD36,
      and E-selectin in cerebral vessels but no cellular inflammatory response. These
      results suggest that these receptors have a role in sequestration in vivo and
      indicate that systemic endothelial activation is a feature of fatal malaria.

PMID- 7526696
TI  - Expression and function of P-glycoprotein in human mesangial cells.
AB  - P-glycoprotein (PGP), responsible for multidrug resistance (MDR) in cancer cells,
      is normally expressed in kidney proximal tubules and mesangium. PGP expression
      and function were studied in human mesangial cell cultures. MDR1 gene expression
      was demonstrated by reverse transcription-polymerase chain reaction. PGP
      expression was determined using MRK16 monoclonal antibody and its function was
      assessed by the efflux of rhodamine-123 (R123). R123 efflux had a half time of 25
      +/- 5 s. Efflux was inhibited by cyclosporin A (10 microM), verapamil (10
      microM), and vinblastine (100 microM) with half times of 380, 535, and 312 s,
      respectively. Incubation with MDR1-antisense oligonucleotide decreased R123
      efflux (half time = 304 s). Verapamil, cyclosporin A, and PSC-833 augmented the
      cytotoxicity of Adriamycin by reducing the 50% maximal growth-inhibitory dose
      from 730 nM to 130, 110, and 90 nM, respectively. We conclude that human
      mesangial cells express MDR1 and demonstrate xenobiotic transport inhibitable by
      several known PGP substrates. Concomitant exposure of mesangial cells to PGP
      transported drugs causes intracellular accumulation of toxic PGP substrates and
      ultimately damages the mesangial cells.

PMID- 7526697
TI  - Interactions between inhibitory and excitatory modulatory signals in single
      submucosal neurons.
AB  - Intracellular recordings were made in submucosal neurons from the guinea pig
      ileum to study the actions of norepinephrine and somatostatin on slow
      depolarizations induced by 2-chloroadenosine (CADO) and substance P. Local
      application (by pressure) of CADO and substance P induced a slow depolarization
      that occurred concomitantly with an increase in input membrane resistance.
      Norepinephrine, UK-14304 (alpha 2-adrenoceptor agonist), and somatostatin blocked
      the excitatory responses induced by CADO in a concentration-dependent manner. The
      alpha 2-adrenoceptor antagonists idazoxan and yohimbine antagonized these
      inhibitory effects of UK-14304 and norepinephrine. UK-14304 also decreased
      depolarizations induced by forskolin, but not those induced by the adenosine
      3',5'-cyclic monophosphate analogue 8-(4-chlorophenylthio)adenosine 3',5'-cyclic
      monophosphate. Slow depolarizations induced by substance P were blocked neither
      by UK-14304 nor by somatostatin. It was previously shown that staurosporine (an
      inhibitor of various protein kinases) and KT-5720 (an inhibitor of protein kinase
      A) inhibited slow depolarizations induced by CADO. Here, substance P
      depolarizations were inhibited by staurosporine and calphostin C (a blocker of
      protein kinase C) but not by KT-5720. In conclusion, activation of alpha 2
      adrenoceptors and somatostatin receptors selectively blocks excitatory responses
      induced by CADO, most likely by inhibition of adenylyl cyclase and via pertussis
      toxin-sensitive G proteins. Slow depolarizations induced by substance P are
      independent of adenylyl cyclase activation and involve activation of protein
      kinase C.

PMID- 7526698
TI  - Regulation of endothelial nitric oxide synthase mRNA, protein, and activity
      during cell growth.
AB  - Cell growth influences the expression of several important tissue-specific
      functions. We sought to examine the effect of cell proliferation on nitric oxide
      (NO) synthase gene expression in cultured aortic bovine endothelial cells.
      Western and Northern blot analysis revealed three- and sixfold increases in NO
      synthase protein and mRNA, respectively, in growing compared with growth-arrested
      cells. The release of nitrogen oxides was also increased in proliferating cells
      compared with growth-arrested cells, as was the NO synthase activity assessed by
      L-arginine/L-citrulline conversion. Neither NO synthase inhibitors nor superoxide
      dismutase affected proliferation or thymidine incorporation, suggesting that
      increased NO release had no effect on endothelial cell growth. In conclusion,
      these studies demonstrate that expression of endothelial cell NO synthase is
      markedly increased in proliferating compared with quiescent nongrowing cells. The
      mechanisms underlying this and its physiological consequences remain to be
      defined.

PMID- 7526699
TI  - Interferon-gamma downregulates CFTR gene expression in epithelial cells.
AB  - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance
      regulator (CFTR) gene, resulting in defective transepithelial Cl- transport. The
      regulation of CF gene expression is not fully understood. We report that
      interferon-gamma (IFN-gamma), but not IFN-alpha or -beta, downregulates CFTR mRNA
      levels in two colon-derived epithelial cell lines, HT-29 and T84, in a time- and
      concentration (from 0.1 IU/ml)-dependent manner. IFN-gamma has no effect on the
      transcription rate of the CFTR gene but reduces CFTR mRNA half-life, indicating
      that it exerts a posttranscriptional regulation of CFTR expression, at least
      partly, through destabilization of the transcripts. Cells treated with IFN-gamma
      contain subnormal amounts of 165-kDa CFTR protein. Assays of adenosine 3',5'
      cyclic monophosphate-stimulated 36Cl- efflux and whole cell currents show that
      CFTR function is diminished in IFN-gamma-treated cells. IFN-gamma and tumor
      necrosis factor-alpha synergistically reduce CFTR gene expression. Our results
      suggest that production of these cytokines in response to bacterial infections
      and inflammatory disorders may alter transmembrane Cl- transport.

PMID- 7526700
TI  - Multiple modes of regulation of airway epithelial chloride secretion by
      extracellular ATP.
AB  - Cultured normal and cystic fibrosis (CF) airway epithelia were exposed to 5'-(N
      ethylcarboxamido)-adenosine (NECA), ATP, or ionomycin. NECA activated a
      sustained, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-insensitive Cl
      secretory response in normal but not CF, consistent with stimulation of the CF
      transmembrane conductance regulator (CFTR). In normal and CF, ionomycin or ATP
      induced Cl- secretion with an initial peak that was inhibited > 50% by DIDS, but
      in normals there was a prolonged current that was not inhibited by DIDS. The ATP
      and ionomycin responses in CF were of greater magnitude, and the prolonged phase
      was inhibited by DIDS. Although we expected ATP to regulate Cl- conductance
      through intracellular Ca2+ activity, ATP further stimulated Cl- secretion in
      tissues pretreated to maximally elevate intracellular Ca2+ activity. ATP also
      activated whole cell Cl- currents in cells dialyzed with 10 mM ethylene glycol
      bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Thus ATP and ionomycin
      regulate a Cl- conductance that is distinct from CFTR, but the regulation by ATP
      is not tightly coupled to intracellular Ca2+ activity. Alternatively, ATP
      regulates separate Ca(2+)-sensitive and Ca(2+)-insensitive Cl- conductances.
      Furthermore, extracellular ATP activates DIDS-resistant Cl- secretion in normal
      but not CF cultured epithelia, consistent with activation of CFTR by
      extracellular ATP.

PMID- 7526701
TI  - Interleukin-1 receptor antagonist prevents sepsis-induced inhibition of protein
      synthesis.
AB  - To understand the role of interleukin-1 (IL-1) as a mediator of the sepsis
      induced skeletal muscle catabolism, we investigated the effects of a specific IL
      1 receptor antagonist (IL-1ra) on skeletal muscle protein metabolism in a rodent
      model of chronic abdominal sepsis. A constant infusion of IL-1ra (2 mg.kg-1.h-1)
      or saline was begun immediately after the induction of sepsis and continued for 5
      days. The effect of IL-1ra on protein metabolism was examined in individual
      muscles (gastrocnemius, soleus, heart) containing different fiber types. Infusion
      of IL-1ra in control animals did not alter protein metabolism in any of the
      muscles examined. Muscle weight, protein content, and the rate of protein
      synthesis in gastrocnemius were reduced by sepsis, whereas none of these
      parameters were affected in soleus or heart. Infusion of IL-1ra prevented the
      sepsis-induced loss of muscle protein and inhibition of protein synthesis in
      gastrocnemius but was without effect in soleus or heart. IL-1ra infusion restored
      translational efficiency in the gastrocnemius of septic rats and was without
      effect on the RNA content. These results provide evidence for a role of IL-1 as a
      mediator of the sepsis-induced abnormalities in skeletal muscle protein
      metabolism.

PMID- 7526702
TI  - Profile of IGF-binding proteins secreted by intestinal epithelial cells changes
      with differentiation.
AB  - Previous reports have shown that gastrointestinal epithelial cells produce
      insulin-like growth factor-binding proteins (IGF-BP), which modulate the actions
      of IGF. This study aims to examine the relationship between differentiation and
      IGF-BP secretion by human intestinal epithelial cells and the effect of growth
      factors on their production. Caco-2 cells were cultured in serum-free media. IGF
      BP secretion into the incubation media was analyzed by Western ligand blotting
      and immunoblotting. Caco-2 cells produced IGF-BP-2, IGF-BP-3, and IGF-BP-4.
      Secretion of IGF-BP-2 and IGF-BP-3 increased with differentiation, but IGF-BP-4
      secretion diminished. The effect of exogenous growth factors on IGF-BP secretion
      was maximal at earlier stages of differentiation. IGF-I stimulated mainly IGF-BP
      3 production, but epidermal growth factor (EGF) and transforming growth factor
      alpha (TGF-alpha) stimulated predominantly IGF-BP-4 secretion. Adding an anti-EGF
      receptor antibody to block autocrine TGF-alpha activity inhibited IGF-BP-4
      production but stimulated IGF-BP-2 and IGF-BP-3. In conclusion, the profile of
      IGF-BP secretion changes with differentiation. IGF-I and EGF (or TGF-alpha)
      stimulate different types of IGF-BP, with autocrine TGF-alpha activity being a
      factor affecting IGF-BP production during differentiation.

PMID- 7526703
TI  - Regulation of type II alveolar epithelial cell proliferation by TGF-beta during
      bleomycin-induced lung injury in rats.
AB  - Three isoforms of transforming growth factor-beta (TGF-beta) are found in
      mammalian cells and are potent regulators of inflammation, connective tissue
      synthesis, cellular proliferation, and differentiation. To determine the
      distribution and regulation of TGF-beta isoforms during pulmonary injury, a rat
      model of bleomycin-induced lung inflammation and repair was used. Using
      immunohistochemistry, we demonstrate that TGF-beta 2 and TGF-beta 3 were
      localized to alveolar macrophages as well as epithelial and smooth muscle cells
      of both normal rat lungs and rat lungs obtained at all time intervals after
      bleomycin administration. Early in bleomycin-induced lung injury, when there is
      active proliferation of type II alveolar epithelial cells, there was an increase
      in the number of type II alveolar epithelial cells isolated per lung and an
      increase in DNA synthesis by explanted type II alveolar epithelial cells. At this
      time, the secretion of biologically active TGF-beta 1-3, which are potent
      inhibitors of epithelial cell proliferation, was decreased. However, the
      secretion of TGF-beta 1-3 activity was markedly increased later in the injury
      response and coincided with a reduction in the number of type II alveolar
      epithelial cells isolated per lung and DNA synthesis in vitro. Furthermore, the
      addition of TGF-beta 1, 2, and 3 to cultures of actively proliferating type II
      alveolar epithelial cells resulted in inhibition of [3H]thymidine incorporation,
      whereas, in the presence of anti-TGF-beta 1-3 antibody, there was an increase in
      [3H]thymidine incorporation. Our findings suggest that altered secretion of TGF
      beta 1-3 activity by type II alveolar epithelial cells during bleomycin-induced
      lung injury may regulate pulmonary alveolar epithelial cell proliferation during
      injury and repair phases.

PMID- 7526705
TI  - Interferon-gamma regulation of interleukin 6 in monocytic cells.
AB  - The regulation of interleukin 6 (IL-6) is dependent on many factors that include
      numerous stimuli such as lipopolysaccharide (LPS), viruses, and other cytokines.
      These studies demonstrate the ability of interferon-gamma (IFN-gamma) to
      significantly enhance IL-6 mRNA and protein production in LPS-stimulated
      monocytes and THP-1 cells. IL-6 protein production was increased sevenfold in LPS
      stimulated cells with the addition of IFN-gamma. IL-6 mRNA production was
      increased in a dose-dependent fashion up to 15-fold in LPS-stimulated cells with
      the addition of IFN-gamma. The enhanced production of IL-6 mRNA that occurs with
      the addition of IFN-gamma to LPS-stimulated monocytic cells was due to increased
      transcription of IL-6 mRNA. The ability of IFN-gamma to enhance IL-6 production
      may play an important role in many inflammatory processes.

PMID- 7526704
TI  - Expression of activation markers by human lung T cells after adherence to lung
      epithelial cells.
AB  - Both increased T cell numbers and their increased activation state have
      implicated an important role for T cells in chronic inflammatory reactions seen
      in the airways of (allergic) asthmatics. Airway epithelial cells are frequently
      exposed to stimuli that cause the release of mediators and the expression of cell
      adhesion molecules. We have examined whether human airway epithelial cells can
      activate lung-derived T cells. Clonal lung T cells showed an increased adherence
      to transformed airway epithelial cells that had been exposed previously for 2 h
      to human recombinant interferon-gamma (IFN-gamma; 100 U/ml). After an additional
      16-24 h of culturing in the absence or presence of epithelial cells, T cells
      expressed increased levels of both the alpha-chain of the interleukin-2 receptor
      (IL-2R, CD25) and the transferrin receptor (CD71), both markers of T cell
      activation. T cells apparently activated by epithelial cells, however, did not
      produce IFN-gamma or IL-4 nor showed an increased proliferation on the addition
      of IL-2 (5-50 U/ml). The induced adherence to and the activation of T cells by
      epithelial cells is mediated largely by CD2 and its ligand lymphocyte functional
      antigen-3, a pathway known to up- and downregulate T cell functions.

PMID- 7526706
TI  - Maturation-related changes in endothelial nitric oxide synthase
      immunolocalization in developing ovine lung.
AB  - It is unknown whether high fetal pulmonary vascular tone is due in part to absent
      or decreased endothelial nitric oxide synthase (eNOS), the enzyme that produces
      nitric oxide in the vascular endothelium. To determine the timing of appearance
      and maturational changes of eNOS in the developing pulmonary circulation, we
      performed immunohistochemistry in lungs from fetal, neonatal, and adult sheep.
      Using a mouse monoclonal antibody against bovine aortic eNOS, we found
      immunoreactive eNOS selectively in the endothelium and it was present at all
      fetal ages. Immunoreactivity was seen as early as 29% gestation in the developing
      capillaries coursing through fetal mesenchyme. By 6 days after birth,
      immunoreactivity was decreased in most vessels and nearly absent in the distal
      pulmonary arteries of adult animals. We conclude that immunoreactive eNOS is
      present very early in fetal life and appears to decrease postnatally. We
      speculate that the early presence of eNOS in the fetal lung supports a possible
      role for endogenous nitric oxide activity in the regulation of vascular tone or
      angiogenesis in the developing pulmonary circulation.

PMID- 7526707
TI  - In situ hybridization localization of mRNA encoding inducible nitric oxide
      synthase in rat kidney.
AB  - We used in situ hybridization with a digoxigenin-labeled cRNA for inducible
      nitric oxide synthase (iNOS) to characterize the intrarenal distribution of iNOS
      transcripts in normal and lipopolysaccharide (LPS)-treated rats. In normal rats,
      the S3 segment of the proximal tubule, the cortical and medullary thick ascending
      limb, the distal convoluted tubule, and the cortical and inner medullary
      collecting duct were intensely labeled, whereas the thin limbs of Henle, proximal
      convoluted tubule, outer medullary collecting duct, and medullary interstitial
      cells were weakly labeled. LPS-treated rats exhibited a similar labeling pattern,
      but with increased staining of mesangial cells, medullary interstitial cells, and
      papillary surface epithelium. The renal vasculature, including the afferent
      arteriole, was not labeled in either group. No cellular labeling was observed
      when the sections were hybridized with the sense iNOS probe. These results
      indicate that iNOS mRNA is tonically and differentially expressed along the
      normal rat nephron and that LPS induces iNOS gene expression in normally
      quiescent mesangial cells, medullary interstitial cells, and papillary surface
      epithelium.

PMID- 7526708
TI  - Induction of resistance to mineralocorticoid hormone in cultured inner medullary
      collecting duct cells by TGF-beta 1.
AB  - The renal collecting duct is a major target for the mineralocorticoid hormone
      aldosterone which acts to enhance electrogenic Na+ absorption. The cortical
      portion of the collecting duct displays a vigorous response to mineralocorticoids
      administered in vivo. The terminal, or inner medullary portion, does not usually
      display such a vigorous response; the reason for this difference is unknown. To
      explore one possible mechanism for this lack of response, we varied the
      conditions of culturing these cells and determined that serum inhibited the
      ability of aldosterone to enhance Na+ transport. By screening 11 peptides, we
      found that transforming growth factor (TGF)-beta 1 produced a concentration
      dependent inhibition of the action of aldosterone. The action of TGF-beta 1
      required at least several hours of incubation. Resistance to the action of
      aldosterone could be produced by preincubating the monolayers with TGF-beta 1 for
      a few hours; subsequent exposure to aldosterone for up to 48 h failed to
      stimulate Na+ transport. TGF-beta 1 did not produce a change in cell morphology
      or the content of DNA, ATP, or ADP; there was a small reduction in protein
      content. Pretreatment with cycloheximide failed to reproduce the TGF-beta 1
      effect. The induction of resistance to mineralocorticoid hormone may play an
      important role in modulating the effects of aldosterone on Na+ homeostasis.

PMID- 7526709
TI  - Bradykinin-induced in vitro contraction of rat mesangial cells via a B2 receptor
      type.
AB  - The effect of bradykinin (BK) on the contraction of rat mesangial cells (MC) was
      compared with that of various vasoactive agents. BK induced a dose-dependent
      contraction [one-half maximal effective dose (ED50) = 50 nM] inhibited by the B2
      antagonist, HOE-140 (ED50 = 10 nM). BK-induced MC contraction was independent of
      extracellular calcium and was reduced by inhibition of protein kinase C (PKC).
      Neomycin completely prevented the increase in intracellular calcium and the
      formation of inositol 1,4,5-trisphosphate induced by BK but only reduced cell
      contraction. Inhibition of prostaglandin (PG) formation and administration of the
      endoperoxide antagonist SQ-27427 also partly decreased the effect of BK.
      Interestingly, only the addition of both neomycin and mepacrine resulted in a
      complete inhibition of cell contraction. These results suggest that BK, via a B2
      kinin receptor, induces contraction of MC through two distinct mechanisms, one
      associated to the phospholipase C pathway and subsequent activation of PKC and
      the second one dependent on PG formation. These in vitro effects may be relevant
      in explaining the effects of BK and converting enzyme inhibitors on glomerular
      hemodynamics.

PMID- 7526710
TI  - Effect of ryanodine on the initiation and perpetuation of stretch-induced
      arrhythmias in isolated canine ventricle.
AB  - Ventricular arrhythmias can be initiated by a mechanism of transient diastolic
      dilation. To test the hypothesis that Ca2+ release from sarcoplasmic reticulum
      (SR) is important in initiation of such stretch-induced arrhythmias (SIAs), we
      studied effects of ryanodine in an isolated canine heart model. Arrhythmias were
      induced by a computerized ventricular volume servo-pump system that transiently
      increased left ventricular volume by precise amounts (delta V) during diastole.
      The probability of eliciting an SIA (PSIA) was compared at the minimum delta V
      that resulted in PSIA of > or = 90% under baseline conditions. Block of SR Ca2+
      release with 10(-5) M ryanodine in 11 ventricles produced mild inhibition of
      SIAs, reducing PSIA by 19.4% (P = 0.039). Because ryanodine produces leakage of
      SR Ca2+ at low concentration and block of SR Ca2+ release at high concentration,
      ryanodine concentration was varied from 10(-9) to 10(-5) M in six ventricles.
      Ryanodine had minimal effect on PSIA over this concentration range. In six
      ventricles with elevated intracellular Ca2+ produced by pretreatment with 0.1-0.3
      microM strophanthidin, 10(-5) M ryanodine did not significantly reduce PSIA.
      Probability of inducing ventricular pairs or nonsustained ventricular tachycardia
      was greater in strophanthidin-treated ventricles than in controls, but induction
      of these repetitive ventricular beats in the strophanthidin group was virtually
      abolished by addition of 10(-5) M ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526711
TI  - In vitro endotoxin exposure induces contractile dysfunction in adult rat cardiac
      myocytes.
AB  - In vivo endotoxin treatment causes a nitric oxide-mediated hypocontractility in
      cardiac myocytes. The objective of this study was to assess whether in vitro
      endotoxin exposure confers similar contractile defects in adult rat cardiac
      cells. We found that incubation of cardiac myocytes for 6 h with 10-100 ng/ml
      endotoxin resulted in progressive time- and protein synthesis-dependent decreases
      in electrically stimulated twitch magnitudes and increased contraction and
      relaxation times. Serum was not required for the endotoxin-induced
      hypocontractility. The endotoxin-induced defect in contractility was reversed
      over time, since myocytes continuously incubated with endotoxin for 24 h
      exhibited normal contractility; in contrast, control cells incubated for 18 h
      were suppressed by a subsequent 6-h exposure to endotoxin. Nitric oxide synthase
      activity was increased after a 6-h endotoxin treatment as evidenced by a dose
      dependent enhanced conversion of [3H]arginine to [3H]citrulline and by elevated
      guanosine 3',5'-cyclic monophosphate levels. Superfusion of endotoxin-incubated
      cells with N omega-nitro-L-arginine methyl ester restored contractile function,
      whereas superfusion with L-arginine reimposed abnormal contractility. Naive
      myocytes superfused with 8-bromoguanosine 3',5'-cyclic monophosphate expressed
      contractile defects similar to those induced by endotoxin. These findings
      demonstrate that endotoxin has direct negative effects on cardiac cell
      contractile function and that induction of NO synthase activity is a primary
      intracellular mediator of the diminished contractility.

PMID- 7526712
TI  - IL-1 inhibits beta-adrenergic control of cardiac calcium current: role of L
      arginine/nitric oxide pathway.
AB  - Modulation of the beta-adrenergic control of cardiac L-type Ca2+ current (Ica) by
      human recombinant interleukin-1 beta (IL-1) was examined in adult guinea pig
      ventricular myocytes using the whole cell voltage-clamp technique. ICa was
      elicited in Cs(+)-loaded myocytes by depolarizing pulses from a holding potential
      of -40 mV. Isoproterenol (0.01 and 1 microM) exposed to myocytes pretreated with
      1 ng/ml IL-1 evoked a significantly smaller increase in ICa density compared with
      control cells. This IL-1-mediated decrease in beta-responsiveness was usually
      observed with pretreatment periods of > 1 h and varied as a function of the L
      arginine concentration of the pretreatment medium. In addition, it was prevented
      by 1) IL-1 receptor antagonist, 2) substituting D-arginine for L-arginine, or 3)
      incubating cells with the nitric oxide synthase inhibitor NG-monomethyl-L
      arginine. Thus the present data illustrate that IL-1 significantly alters the
      beta-adrenergic control of cardiac Ca2+ channels by cellular mechanisms that
      involve the activation of nitric oxide synthase. These mechanisms may play a role
      in altering ventricular function during cytokine-mediated inflammatory processes
      affecting the heart.

PMID- 7526713
TI  - Modulation of left ventricular relaxation in isolated ejecting heart by
      endogenous nitric oxide.
AB  - Nitric oxide (NO) modulates myocardial contractile behavior in several isolated
      preparations, e.g., cardiac myocytes and papillary muscles, via elevation of
      intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We have recently
      reported that the exogenous NO donor, sodium nitroprusside, selectively modulates
      left ventricular (LV) relaxation in the isolated ejecting guinea pig heart,
      independent of coronary flow. We now report the effects of endogenously released
      NO on LV performance in this preparation (constant heart rate and loading). Both
      bradykinin (1 nM, n = 6) and substance P (100 nM, n = 6) accelerated early LV
      relaxation (maximum change in time constant, tE, -10.5 +/- 1.6 and -13.4 +/-
      2.1%, respectively; both P < 0.05), without significantly altering early systolic
      parameters (e.g., rate of LV pressure development). These effects were inhibited
      by hemoglobin (P < 0.05; n > or = 6), which inactivates NO. Bradykinin (100 nM, n
      = 10) had an additional negative inotropic effect, which was not inhibited by
      hemoglobin. Neither agonist altered relaxation in isolated papillary muscles.
      These data suggest that endogenous NO, probably released from coronary
      microvascular endothelial cells, modulates LV relaxation in the intact heart.

PMID- 7526714
TI  - Hypoxia inhibits expression of eNOS via transcriptional and posttranscriptional
      mechanisms.
AB  - Normal blood vessel tone is maintained by a balance of vasoconstrictors and
      vasodilators produced by endothelial cells in the vasculature. Nitric oxide (NO)
      is a potent vasodilator that causes vascular smooth muscle cell relaxation by
      elevating intracellular guanosine 3',5'-cyclic monophosphate (cGMP) levels. The
      physiological mechanisms regulating NO production in the vasculature are not
      completely understood. We report here that production of this vasodilator by
      vascular endothelial cells can be significantly suppressed by hypoxia. Exposing
      human endothelial cells to low PO2 results in 40-60% reduction in the steady
      state mRNA levels of endothelial constitutive NO synthase (eNOS), the major
      enzyme responsible for NO production in these cells. The lower levels of eNOS
      mRNA result from decreased transcription of the gene as well as reduced message
      stability. In endothelial-smooth muscle cell co-culture experiments, hypoxic
      endothelial cells stimulated significantly less cGMP production by smooth muscle
      cells than the corresponding normoxic controls. This inhibitory effect of hypoxia
      on NOS production by endothelial cells occurs after 24 h of hypoxia and persists
      for at least 48 h. These new findings suggest that hypoxia might cause changes in
      blood vessel tone through compound mechanisms: by increasing the production of
      endothelium-derived vasoconstrictors and, as shown here, by suppressing the
      production of vasodilators like NO.

PMID- 7526716
TI  - ATP promotes development of afterdepolarizations and triggered activity in
      cardiac myocytes.
AB  - The effect of extracellular ATP on transient inward current (Iti), delayed
      afterdepolarization (DAD), early afterdepolarization (EAD), and triggered
      activity were investigated in guinea pig isolated ventricular myocytes. ATP alone
      did not induce afterdepolarizations nor did it significantly alter the resting
      membrane potentials and action potentials. However, when it was applied with
      drugs known to increase intracellular Ca2+, ATP facilitated the induction of
      afterdepolarizations and triggered activity in approximately 60% of the cells. In
      the presence of isoproterenol, ATP increased the amplitude of Iti and DADs by 55
      and 206%, respectively, and caused increases in the amplitude of L-type Ca2+
      current (ICa) and EADs, which occasionally led to triggered activity. Similarly,
      addition of ATP increased the amplitude of Iti and DADs induced by elevated
      extracellular Ca2+ by 110 and 83%, respectively. Ryanodine inhibited the ATP
      induced increase in Iti but not the increase in ICa. In the presence of BAY K
      8644 or quinidine, ATP not only further prolonged the action potential durations
      by 18 +/- 4 and 17 +/- 4%, respectively, but also increased the amplitude of
      EADs. The present results show a novel arrhythmogenic effect of extracellular
      ATP, which facilitates the genesis of triggered arrhythmias when Ca2+ influx is
      increased, probably by further increasing Ca2+ influx from extracellular medium
      and Ca2+ release from intracellular stores.

PMID- 7526715
TI  - Thrombin receptor-mediated vascular relaxation differentiated by a receptor
      antagonist and desensitization.
AB  - The vasorelaxant actions of the serine protease, alpha-thrombin, are selectively
      blocked by the thrombin active site inhibitors, suggesting that proteolytic
      cleavage is required for alpha-thrombin-induced release of nitric oxide. Whether
      these relaxations are caused by interaction with a thrombin receptor was
      evaluated using a prototype thrombin receptor antagonist, a decapeptide analogue
      of the tethered ligand thrombin receptor [3-mercapto-propionyl-Phe-Cha-Cha-Arg
      Lys-Pro-Asn-Asp-Lys-amide (c186-65)]. In rings of pig coronary arteries with
      endothelium contracted submaximally with U-46619, the relaxation caused by
      extremely low concentrations of alpha-thrombin were mimicked by the synthetic
      thrombin receptor-activating peptide (TRAP-7: SFLLRNP). These relaxations were
      inhibited by C186-65. In contrast, C186-65 had no effect on the relaxations
      caused by bradykinin and serotonin. Exposure of arteries to alpha-thrombin or
      TRAP-7 caused heterologous desensitization to subsequent stimulation by alpha
      thrombin or TRAP-7 but not by bradykinin. These studies support the hypothesis
      that alpha-thrombin-induced endothelium-dependent relaxations occur by activation
      of the cloned "tethered-ligand" thrombin receptor in vascular endothelium.

PMID- 7526717
TI  - Substance P, calcitonin gene-related peptide, and capsaicin release serotonin
      from cerebrovascular mast cells.
AB  - Rabbit leptomeningeal arteries contain granular cells resembling mast cells that
      frequently contact autonomic and sensory nerve profiles. In the present in vitro
      study, we determined whether these cells could be stimulated by substance P (SP)
      and calcitonin gene-related peptide (CGRP), which are stored and released by
      sensory C fibers. Immunohistochemistry of the middle cerebral artery showed that
      5-HT was stored only in mast cell-like granules. This pool of 5-HT decreased in a
      dose-dependent manner when exogenous SP and CGRP were added to the incubation
      solution or when endogenous neuropeptides were released from nerve terminals by
      capsaicin. The simultaneous administration of CGRP and SP induced a dramatic
      exocytosis and a 5-HT release significantly greater than the sum of the
      individual effects of the two neuropeptides. We conclude that, as in classical
      connective tissue mast cells, the amine content of these granular cells can be
      released by a degranulation process induced by neuropeptides. The effects of
      capsaicin suggest that this phenomenon can be triggered by axon reflex of C
      fibers. The data also provide the first evidence of a synergistic action of SP
      and CGRP on mast cell degranulation.

PMID- 7526719
TI  - Computer-assisted image analysis of tumor sections for a new thrombospondin
      receptor.
AB  - BACKGROUND: A cell surface receptor (50 kd) has been recently identified in
      malignant cells that recognizes the tumor cell adhesive domain (ie, cysteine
      serine-valine-threonine-cysteine-glycine [CSVTCG]) of thrombospondin (TSP). This
      CSVTCG-specific TSP receptor can be considered as a new tumor marker, and its
      concentration on the cell surface may correlate directly with the capacity of
      tumor cells to invade and metastasize. MATERIALS AND METHODS: Six patients with
      primary, stages III and IV squamous cell carcinomas of the head and neck were
      studied. Tumor sections were specifically stained for this receptor with
      immunohistochemical techniques. The stained specimens were then subjected to
      computer-assisted image analysis. The area of positive staining and the
      heterogeneity of the pattern of staining were compared to peritumoral
      angiogenesis and clinical outcome of the patients. RESULTS: The results indicate
      that those patients with a high and homogenous positive stain score (mean +/-
      standard error [SE] 78 +/- 5%) for the CSVTCG-specific TSP receptor had high
      microvessel density and died from metastatic disease within 12 months of initial
      treatment (correlation coefficients = 0.95 and 1, respectively). Patients with a
      low and heterogenous positive stain score for receptor (mean +/- SE 8 +/- 2%; P <
      0.001) had low microvessel counts and remained disease-free for at least 2 years.
      There was no relationship between receptor density and histologic classification
      of the primary tumors. CONCLUSION: The CSVTCG-specific TSP receptor, quantified
      through image analysis of immunohistochemical stained tissue sections, is highly
      predictive of clinical outcome in patients with squamous cell carcinomas of the
      head and neck.

PMID- 7526720
TI  - Expression of human intercellular adhesion molecules in middle ear cholesteatoma.
AB  - INTRODUCTION: Cell adhesion molecules are cell surface proteins that allow
      specific cell-cell interactions among leukocytes, as well as between leukocytes
      and other cells. Because middle ear cholesteatoma is characterized by the
      presence of leukocyte infiltrates, the presence of the two molecule types of
      intercellular adhesion molecules (ICAM-1 and ICAM-2) was investigated on
      cholesteatoma using monoclonal antibodies. METHODS: Tissue sections from 10
      patients with cholesteatoma, and normal skin from 5 patients were prepared for
      alkaline-phosphatase--anti-alkaline-phosphatase (APAAP) staining. RESULTS: ICAM-1
      and ICAM-2 were present in normal skin in microvascular endothelial cells and in
      intersticial cells of the dermis. Cholesteatoma showed a very important increase
      of the ICAM-1 expression with comparison to human skin. All infiltrating immune
      cells showed positive reactions for the antibody. Furthermore, the intensity of
      the staining of vessels cells was higher than in normal skin. Keratinocytes were
      only positive if a very heavy infiltrate was present subepidermally. ICAM-2 was
      present in endothelial and intersticial cells in normal skin and in
      cholesteatoma. Most of the infiltrating cells in the cholesteatoma stroma showed
      positive reactions for the anti-ICAM-2 antibody. CONCLUSION: Our results suggest
      that both ICAM-1 and ICAM-2 play a central role in the regulation of the
      inflammatory disorders observed in cholesteatoma.

PMID- 7526718
TI  - Tumor angiogenesis as a prognostic factor in oral cavity tumors.
AB  - BACKGROUND: Lymph-node metastasis is the single greatest predictor of survival in
      patients with oral cavity cancers. Tumor angiogenesis has been correlated with
      metastasis in breast cancer and may have prognostic value in other tumors.
      PATIENTS AND METHODS: Sixty-six patients with clinically node-negative oral
      cavity squamous cell cancers were reviewed. Samples were cut and stained for
      factor VIII. The percentage of area of tissue stained for factor VIII was
      quantitated by a computerized image analyzer. Tumor depth was measured with an
      ocular micrometer to the nearest 0.1 mm. Variables were statistically examined
      against regional recurrence. RESULTS: The probability of metastasis (%) was 2 for
      tumor staining of < or = 10% and 93 for tumor staining > 10% (P < 0.0001). The
      tumor depth was < or = 4 mm in 10 and > 4 mm in 83 (P < 0.0001). Patients with <
      or = 4 mm and < or = 10% staining had a 2% rate of recurrence, and patients with
      > 4 mm and > 10% staining had a 100% rate of recurrence (P < 0.0001). CONCLUSION:
      Although tumor thickness was suggestive of predictability, only angiogenesis was
      a statistically significant predictor of recurrence in a multivariate analysis (P
      < 0.0001). Angiogenesis showed a strong correlation with regional recurrence and
      may be used as an independent prognostic indicator.

PMID- 7526722
TI  - Recombinant human granulocyte colony stimulating factor in cyclic neutropenia:
      use of a new 3-day-a-week regimen.
AB  - BACKGROUND: G-CSF has been shown to be beneficial in cyclic neutropenia when
      given as a daily subcutaneous injection. We investigated the usefulness of a new
      three-day-a-week regimen. METHODS: A ten year old boy with cyclic neutropenia was
      initially treated with G-CSF 7 micrograms/kg given on alternate days for seven
      months. He was then placed on the same dose, given three days a week. The
      effectiveness of these regimens were assessed by serial CBCs and by the frequency
      and duration of the symptoms. RESULTS: The mean absolute neutrophil count (ANC)
      increased from 1282 before therapy to 11,718/microliters on alternate day regimen
      and 7716/microliters on three-day-a-week regimen. The nadir ANC improved from
      30/microliters before therapy to 546/microliters and 198/microliters on
      treatment. The duration and frequency of mouth sores were significantly less on
      therapy, and there was an estimated cost savings of $23,826/year on three-day-a
      week regimen compared to a daily regimen. CONCLUSION: The three-day-a-week G-CSF
      regimen is clinically effective and cost saving in the treatment of cyclic
      neutropenia and should be studied in a larger cohort of patients.

PMID- 7526721
TI  - Effect of basic fibroblast growth factor on normal tympanic membrane.
AB  - PURPOSE: Basic fibroblast growth factor (bFGF) is mitogenic for the cell types
      that constitute the tympanic membrane and has been shown to potentiate tympanic
      membrane healing. The purpose of this study is to investigate the direct effect
      of bFGF application on normal tympanic membrane. MATERIALS AND METHODS: bFGF was
      applied to the normal tympanic membrane of 10 guinea pigs via either the external
      auditory external canal or the middle ear. The drug (400 ng) was delivered on
      days 0, 1, and 2. The contralateral ear was used as a control. The effects were
      assessed on day 3. RESULTS: The cumulative area and the average area of blood
      vessel in each session of TM was greater after bFGF application than placebo. The
      number of vessels remained unchanged. A proliferation of keratinocytes was
      observed. CONCLUSION: These results suggest that bFGF induces a vasodilatation in
      the tympanic membrane thereby increasing blood supply. This might explain the
      acceleration of healing of TM perforations after bFGF application.

PMID- 7526723
TI  - On the discriminatory value of anti-HPCA-1 (CD-34) in the differential diagnosis
      of benign and malignant cutaneous vascular proliferations.
AB  - The staining pattern of monoclonal antibody anti-HPCA-1 (CD-34) was studied in 95
      cases of benign and malignant cutaneous vascular proliferations and compared with
      other vascular endothelium-associated antigenic markers in paraffin-embedded
      tissues. The proliferating vessels in 22 cutaneous capillary hemangiomas, 8
      lobular capillary hemangiomas, and 1 case of papillary intravascular endothelial
      hyperplasia stained strongly positively for anti-HPCA-1, and the intensity of the
      reaction was paralleled by that of factor VIII-related antigen (FVIII), Ulex
      europaeus lectin-1 (UEA), and vimentin (VIM). The vessels in 10 cases of
      granulation tissue, 6 cases of cavernous hemangioma, 6 cases of angiokeratoma, 5
      cases of angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma),
      and 3 cases of bacillary angiomatosis showed a lack of reactivity with anti-HPCA
      1 and staining of variable intensity with the other markers. Twenty cases of
      Kaposi's sarcoma (seven patch, five plaque, eight nodular stage) showed strong
      labeling with anti-HPCA-1 in small, well-formed vessels scattered among the
      spindle-cell proliferation, and four of these cases showed focal positivity of
      scattered spindle cells. Nine cases of cutaneous angiosarcoma, two cases of low
      grade epithelioid angiosarcoma, and one case of spindle-cell hemangioendothelioma
      were negative for anti-HPCA-1 and showed variable reactivity for FVIII and UEA;
      all cases stained strongly positively for VIM. The results of this study indicate
      that although anti-HPCA-1 shows a high sensitivity for the staining of normal
      vascular endothelium, its specificity may be restricted to mature, well-formed
      vessels, therefore rendering its discriminatory value very limited for the
      identification of poorly differentiated vascular endothelial neoplasms.

PMID- 7526725
TI  - Alcohol, marijuana, and tobacco: effects of prenatal exposure on offspring growth
      and morphology at age six.
AB  - Little is known about the long-term effects of prenatal exposure to alcohol.
      There are even fewer reports on the longitudinal effects of exposure to either
      marijuana or tobacco during pregnancy. This study is on the 6-year follow-up of
      668 children enrolled in the Maternal Health Practices and Child Development
      Project. Mothers were interviewed at the 4th and 7th months of pregnancy, and
      mothers and children were evaluated at delivery, 8, and 18 months, and 3 and 6
      years postpartum. At 6 years of age, children who were exposed to alcohol
      prenatally were significantly smaller in weight, height, head circumference, and
      palpebral fissure width. These effects on size were mediated by the effect of
      prenatal alcohol exposure on the offspring at 8 months. Prenatal alcohol exposure
      was also significantly associated with maternal reports of the child's appetite
      at 6 years. There were no effects of prenatal marijuana or tobacco exposure on
      growth when the children were age 6. There were also no significant relationships
      between prenatal exposure to alcohol, marijuana, or tobacco and the rate of
      morphologic anomalies, including the features of the fetal alcohol syndrome.

PMID- 7526724
TI  - AgNOR area measurements differentiate benign and malignant melanocytic lesions
      more accurately than simple counting.
AB  - Comparison of argyrophilic nucleolar organizer region (AgNOR) counts has been
      found to yield statistically significant differences between benign and malignant
      conditions albeit with considerable overlap. In this study we compared the size
      of AgNORs and the nuclear areas, as well as the AgNOR count in 23 benign
      melanocytic lesions and 9 melanomas. Of these parameters, the ratio AgNOR
      area/nuclear area was found to be the main discriminating factor between melanoma
      and all the other benign groups studied, with p values of < 0.01 and no overlap.
      Next to it was the nuclear area, which in our study gave significant differences
      between the groups evaluated. The total AgNOR area and the largest AgNOR gave
      results comparable to the simple AgNOR counting in all groups studied, except in
      Spitz nevus, in which the AgNOR counts were less significant than the other
      parameters (p = 0.0420). We conclude that the ratio AgNOR area/nuclear area
      discriminates benign from malignant melanocytic lesions better than AgNOR counts
      or other parameters studied.

PMID- 7526726
TI  - Limited postnatal ethanol exposure permanently alters the expression of mRNAS
      encoding myelin basic protein and myelin-associated glycoprotein in cerebellum.
AB  - Experiments were designed to test the hypothesis that ethanol exposure during
      development can selectively affect the expression of specific isoforms of myelin
      protein gene expression in the rat cerebellum. We focused on myelin basic protein
      (MBP) and myelin-associated glycoprotein (MAG) gene expression. Both of these
      genes are alternatively spliced to yield 4 (MBP) or 2 (MAG) mRNA isoforms.
      Prenatal ethanol exposure, delivered to the dams in a liquid diet, did not
      significantly alter the expression of MBP or MAG gene expression in the
      cerebellums of 15-day-old pups, as measured by quantitative in situ hybridization
      using specific oligodeoxynucleotide probes. In contrast, postnatal ethanol
      exposure delivered directly to the pups over a 6-day period by gastrostomy tube
      (PN days 4-10) reduced the expression of specific MBP and MAG isoforms in the
      cerebellum of animals in adulthood. These data demonstrate that ethanol exposure,
      especially during the period of rapid myelination, has selective effects on mRNA
      isoforms encoding specific MBPs and MAG.

PMID- 7526728
TI  - Anaesthesia for laser prostatectomy.
AB  - A retrospective review was undertaken to examine current anaesthetic practice in
      a single institution for the management of patients undergoing laser ablation of
      the prostate for benign prostatic hypertrophy at St Vincent's Private Hospital,
      Melbourne. Two groups of patients (totalling 72) were identified, one undergoing
      the surgery with a regional anaesthetic technique and a smaller group on full
      anticoagulant therapy for associated medical problems where general anaesthesia
      was preferred.

PMID- 7526727
TI  - Effects of nitric oxide-related agents on alcohol narcosis.
AB  - To examine whether nitric oxide (NO) affects alcohol (ethanol) narcosis, adult
      male rats were pretreated with a NO synthase (NOS) inhibitor, NG-nitro-l-arginine
      methyl ester (NAME); a NOS substrate, l-arginine methyl ester (AME); or a NO
      donor, isosorbide dinitrate (ISDN); then treated with anesthetic doses (3-5 g/kg,
      ip) of alcohol. Pretreatment with NAME (30-100 mg/kg, sc) 40 min before alcohol
      treatment delayed the onset of alcohol-induced loss of the righting reflex (LORR)
      and increased the duration of the LORR. NAME (100 mg/kg) pretreatment combined
      with high doses of alcohol (4-5 g/kg) exerted significant lethal effects, even
      though treatment with either agent alone or NAME combined with lower doses of
      alcohol (3-3.5 g/kg) was not lethal. Simultaneous treatment with the NOS
      substrate AME (100 mg/kg, subcutaneous) blocked the effects of NAME on LORR
      duration times, but did not alter LORR onset times. The NO donor ISDN (30 mg/kg)
      given by oral gavage 2 hr before alcohol decreased LORR duration times without
      affecting the onset of LORR. In addition, ISDN dose-dependently inhibited NAME
      induced LORR duration increases during alcohol narcosis without significantly
      altering LORR onset times. Neither ISDN nor NAME significantly altered blood
      alcohol concentrations. These results suggest that NOS inhibition and subsequent
      decreases in NO production enhance alcohol-induced narcosis and that increases in
      NO concentrations inhibit alcohol narcosis, supporting the hypothesis that
      inhibition of arginine-NOS-NO systems mediates part of the sedative-hypnotic
      effect of alcohol.

PMID- 7526729
TI  - Damage induced in episomal EBV DNA in Raji cells by antitumor drugs as measured
      by pulsed field gel electrophoresis.
AB  - The studies described below were carried out to analyze the damage induced by DNA
      active drugs to episomal (Epstein-Barr virus, EBV) DNA in the Raji Burkitt's
      lymphoma cell line. This work: (i) applies pulsed-field gel electrophoresis
      (PFGE) techniques to quantify DNA damage on a large (approximately 180 kbp),
      circular target, (ii) investigates the DNA strand-scission behavior of different
      classes of drugs on the EBV episome, and (iii) compares EBV episomal damage to
      that generated in genomic DNA in the Raji cell line. Cells were treated with
      ionizing radiation to induce random strand scission, and the migration of
      topological forms of EBV was measured using PFGE. DNA damage induced in the
      episome by DNA active drugs was then assayed. Three drugs, acting by different
      types of DNA interactive mechanisms, were used: bleomycin, an intercalative DNA
      strand-scission agent; and amsacrine (mAMSA) and teniposide (VM26), intercalative
      and nonintercalative topoisomerase II active drugs, respectively. Rad equivalency
      of damage was determined by comparing the drug-induced change in percentage of
      Forms I and III to that generated by ionizing radiation. Additionally, single-
      and double-strand scission induced in genomic (total cellular) DNA by X-rays,
      bleomycin, amsacrine, and teniposide were assayed by high-sensitivity alkaline
      and neutral filter elution techniques. We demonstrate that pulsed-field gel
      electrophoresis is a useful technique for measuring form conversion in large
      episomal DNA. While all three drugs effect both episomal and genomic DNA strand
      scission, bleomycin appears to preferentially damage the EBV episome. The
      topoisomerase II active drugs mAMSA and VM26 show no evidence of episome-directed
      damage in this system and, in fact, damage genomic DNA at somewhat higher rates.

PMID- 7526730
TI  - Detection of dopachrome isomerase activity on gels.
AB  - Dopachrome isomerase is a recently discovered enzyme associated with the
      melanogenesis process occurring in most vertebrates and invertebrates. It
      catalyzes the conversion of dopachrome to 5,6-dihydroxyindole(s). Based on the
      fact that 5,6-dihydroxyindoles are rapidly oxidized to melanochrome pigment by
      tyrosinases, we have developed a rapid, sensitive, and specific staining
      procedure for detection of dopachrome isomerase activity after gel
      electrophoresis. The method employs the use of commercially available mushroom
      tyrosinase entrapped in polyacrylamide gels for electrophoretic separation of
      dopachrome isomerase. Staining is achieved by the use of dopa solution. The
      dopachrome formed by the action of mushroom tyrosinase entrapped in the gel is
      converted to 5,6-dihydroxyindole(s) by dopachrome isomerase initially. The latter
      compound is subsequently oxidized by tyrosinase to purple-colored melanochrome.
      Therefore, dopachrome isomerase appears as a bluish-purple band against a pale
      orange-red background within 10 min. With the use of the new detection technique,
      the presence of hitherto unknown isozymes of dopachrome isomerase could be
      readily detected in polyacrylamide gels. This procedure is more sensitive than
      silver staining for detection of dopachrome isomerase and as little as 15 ng of
      purified protein could be easily detected on gels.

PMID- 7526731
TI  - Estimation of redox properties of chemical compounds by their reactions with free
      radicals.
AB  - The electron-donor and electron-acceptor properties of biologically active
      compounds were estimated on the basis of their reactions with free radical
      intermediates of the excited dye eosin. After dye excitation by a short flash of
      light, the kinetics of dye anion radicals in the pure dye solution were compared
      with those in the presence of the natural reducing agent NADH or a number of
      substances which are known as local anesthetics (LA). LA individually slowed the
      decay of dye anion radicals and enhanced their concentration to a lesser extent
      than NADH, thus acting as electron donors toward dye radicals. The electron-donor
      properties of LA studied correlate with their ability to block sodium channels.
      In contrast, the sodium channel agonist veratridine decreased the concentration
      of dye anion radicals, thus showing electron-acceptor properties. The opposite
      redox features of the channel antagonist and the agonist were revealed also by a
      modified method suitable for steady-light spectroscopy. Promoted by NADH, eosin
      photobleaching was slowed by the electron acceptor ferricyanide as well as by
      veratridine and some phenols. The electron-acceptor properties of the latter
      compounds correlated with their ability to inhibit ATP synthesis by
      submitochondrial particles. Thus, these methods may be used to evaluate the redox
      properties of compounds not characterized by electrochemical methods and to
      predict their biological activity.

PMID- 7526732
TI  - The RNA-polymerase chain reaction technique for alpha and beta myosin heavy
      chain.

PMID- 7526733
TI  - Self-staining of polyunsaturated fatty acids in argentation thin-layer
      chromatography.

PMID- 7526734
TI  - Reverse-transcription polymerase chain reaction for selective detection of RNA of
      single polarity: the role of reverse-transcription incubation temperature.

PMID- 7526735
TI  - A method for the covalent conjugation of antibody to congo red-stained yeast
      cells.

PMID- 7526736
TI  - Reversed-phase high-performance liquid chromatography and capillary
      electrophoresis in the stability study of the neuropeptide growth factor
      antagonist [Arg6,D-Trp7,9,MePhe8]-substance P (6-11): a comparative study.
AB  - Reversed-phase high-performance liquid chromatography and capillary zone
      electrophoresis are widely used in protein and peptide analysis. Degradation of
      the basic peptide [Arg6,D-Trp7,9,MePhe8]-substance P (6-11) (antagonist G) was
      monitored with reversed-phase high-performance liquid chromatography, free
      capillary zone electrophoresis, and capillary zone electrophoresis with a
      capillary cationic coating. Capillary zone electrophoresis with a dynamically
      coated capillary provided better separation between antagonist G and its
      degradation products (formed at pH/Hv 13) than high-performance liquid
      chromatography and free zone capillary electrophoresis. Rate constants of the
      alkaline degradation of antagonist G measured with reversed-phase high
      performance liquid chromatography and capillary zone electrophoresis with a
      dynamic coated capillary wall are similar whereas the values measured with free
      zone capillary electrophoresis are lower. Rate constants for the degradation of
      antagonist G in acidic media are comparable for the three techniques. It is
      concluded that capillary zone electrophoresis using a dynamic coating with
      Fluorad is the most suited of the above-mentioned techniques in analyzing
      antagonist G and its degradation products.

PMID- 7526737
TI  - Characterization of glycoprotein oligosaccharides using surface plasmon
      resonance.
AB  - Surface plasmon resonance was used to characterize the carbohydrate moieties of
      bovine fetuin. This technique, requiring no sample derivatization or labeling,
      identified the presence and composition of both N- and O-linked oligosaccharides,
      using a combination of lectin probes and in situ glycosidase digestion. A
      complete analysis was achieved using 1.4 micrograms of pure bovine fetuin, and
      was fully automated using Pharmacia's BIA-core. The presence or absence of
      specific oligosaccharide structures was determined by the binding of a panel of
      unlabeled lectins. Monosaccharide order and linkages were determined by
      sequential digestion using a range of specific exoglycosidases. This novel method
      implementing in situ digestion was achieved using a modification to the BIAcore
      software, allowing the flow of reagent over the sensor chip to be stopped for
      variable lengths of time, thereby permitting enzymatic digestion to occur. This
      technique can be applied to other commercial SPR biosensors currently available.
      Glycoanalysis by SPR uses approximately 100- to 1000-fold less protein than
      comparable analyses using alternative techniques such as gel permeation
      chromatography of released oligosaccharides, labeled lectin binding, or mass
      spectrometry.

PMID- 7526739
TI  - Quantification of mRNA in human tissue using fluorescent nested reverse
      transcriptase polymerase chain reaction.
AB  - We report the development of a quantitative nested reverse-transcriptase
      polymerase chain reaction which utilizes a fluorescence detection system. Using
      specific primer pairs to study mRNA for endothelin receptors in the human kidney,
      we synthesized a cRNA construct containing the same sequences but yielding a PCR
      product some 300 base pairs larger than native mRNA. Inclusion of a known amount
      of construct as internal standard with tissue RNA prior to cDNA synthesis allowed
      all reactions to occur under the same conditions in the same tube. In the nested
      PCR reaction, serial dilutions made before the second round enabled construction
      of a standard curve for each assay, and confirmation that standard and sample
      curves remained parallel. This indicates that both cDNAs amplified at the same
      rate. One internal primer was fluorescently labeled. Quantification of products
      using an ABI 373A sequencer with Genescan software gave sensitive and
      reproducible results. Analysis of a needle biopsy (10 mg) of histologically
      normal cortex gave 0.4 amol ETA mRNA and 1.6 amol ETB mRNA/micrograms total RNA.
      In medulla these values were 0.46 and 1.16 amol/micrograms, respectively. Ratios
      of ETB to ETA message were 74:26 in cortex and 77:23 in medulla, agreeing with
      previous ligand binding studies of receptor protein. Intra- and interassay
      coefficients of variation were 4.5 and 5.3%. This new method has potential for
      widespread application to the study of low copy-number mRNA or where only very
      small amounts of tissue are available, such as biopsy specimens.

PMID- 7526738
TI  - Metal chelates as reversible stains for detection of electroblotted proteins:
      application to protein microsequencing and immunoblotting.
AB  - Coomassie brilliant blue and Ponceau red have traditionally been used to stain
      electroblotted proteins, since they are compatible with existing N-terminal and
      internal protein microsequencing as well as with immunoblotting procedures. With
      recent improvements in sequencing and immunoblotting technology, detection of
      significantly smaller amounts of protein has become necessary. Metal complexes
      were evaluated as alternatives to conventional stains. Electroblotted proteins
      were detected by blocking nonspecific sites with polyvinylpyrrolidone-40 followed
      by incubation in metal chelate solutions at acidic pH values. Two of the most
      promising metal chelate stains were the Ferrozine/ferrous complex and the
      ferrocyanide/ferric complex. Both stained a wide variety of proteins and peptides
      quantitatively. Dot blots and 1D and 2D electroblots were successfully stained
      using iron chelates. When these two stains were utilized in combination, they
      were of equivalent sensitivity to colloidal gold stain. The reversibility of the
      metal chelate stains was substantiated by incubating stained membranes at neutral
      to basic pH in the presence of 20 mM ethylenediaminetetraacetic acid to rapidly
      elute the complexes from the bound proteins. The chelate stains were determined
      to be fully compatible with immunoblotting, N-terminal, and in situ internal
      protein microsequencing.

PMID- 7526740
TI  - In vitro transcription: preparative RNA yields in analytical scale reactions.
AB  - A new method of in vitro transcription with the use of SP6, T7, and T3 RNA
      polymerases is described. The method makes it possible to obtain, using only 1.6
      2.6 micrograms of DNA template in as little as 50 microliters of transcription
      reaction in just 2 h, more than 200 micrograms of pure mRNA (with high
      translatability). Optimal conditions for the synthesis by all three RNA
      polymerases of transcripts 1500-1700 nt long and also for very long transcripts
      were determined. Reaction conditions that minimize DNA template or RNA polymerase
      requirements are also described, and these provide synthesis of either 1200-2100
      RNA copies per DNA molecule or more than 5-15 micrograms of RNA per unit of RNA
      polymerase. Reactions can be easily scaled up to volumes of several milliliters,
      yielding up to 5.2 mg/ml of 1500- to 1700-nt-long RNA or up to 7.1 mg/ml of very
      long RNA.

PMID- 7526741
TI  - Transfer solution chemistry affects mixed-phase hybridizations.

PMID- 7526742
TI  - Infrared multiphoton dissociation of large multiply charged ions for biomolecule
      sequencing.
AB  - Characterization and verification of the structures of large biomolecules with
      high-resolution tandem Fourier transform mass spectrometry with electrospray
      ionization is critically dependent on the technique used to fragment the multiply
      charged ions produced. Infrared multiphoton dissociation (IRMPD) of ionized
      proteins as large as carbonic anhydrase (29 kDa) yields fragment information
      similar to, but with valuable additions to, that of other dissociation
      techniques. IRMPD yields product ions on-axis, providing efficient dissociation
      in further stages; MS3 of ubiquitin (8.6 kDa) yields 11 new sequence ions.
      Optimum irradiation times for protein ion dissociation vary by more than a factor
      of 6, with times for oligonucleotides far lower, possibly due to photon resonance
      with a P-O stretching frequency. IRMPD provides far greater selectivity than
      collisionally activated dissociation and also appears to yield much less mass
      discrimination and to dissociate much more stable ions. A technique to remove
      product ions on formation from the laser beam should improve the present
      efficiencies of 30-80%.

PMID- 7526743
TI  - Apical cell escape from the neuroepithelium and cell transformation during
      terminal lip fusion in the house shrew embryo.
AB  - The house shrew embryo has many cells in the ventricular lumen and on the luminal
      surface of the fusing terminal lip of the cephalic neural tube. The origin and
      fate of these cells were studied by means of light and electron microscopy, and
      by DiI labeling in a whole-embryo culture system. The cells appeared at stage 11A
      and persisted until stage 12A. Most of the cells seemed to originate from the
      neuroepithelium, as shown by frequent observations of epithelial cell escape and
      DiI labeling analysis. The cells on the luminal surface sometimes showed
      apoptotic features, but were not subjected to phagocytosis. Some of the escaping
      cells seemed to migrate to the ventral part of the prosencephalic neuropore and
      insert themselves into it. Others separated from the luminal surface and floated
      into the lumen. It seems likely that the floating cells either become autolyzed,
      or else change into macrophage-like cells, the latter alternative being supported
      by the results of DiI labeling. The macrophage-like cells actively phagocytosed
      the other degenerating cells and apoptotic bodies. These observations suggest
      that the apical escape of cells may play an important role in the remodeling of
      the neural fold during the terminal lip fusion, and that early neuroepithelial
      cells may have the potential to become cells with vigorous phagocytic activity,
      like macrophages.

PMID- 7526745
TI  - Development of nucleolar apparatus in the chick primitive erythroid cells.
AB  - The primitive erythroid line cells of chick embryos were studied during embryonic
      days 2-14 by means of a cytochemical method to investigate the appearance and
      frequency of the main nucleolar types. The populations of erythroblasts and
      erythrocytes were classified according to the presence of functionally dominant
      nucleoli in their nuclei. In the course of primitive erythroid cell
      differentiation and maturation, compact nucleoli and nucleoli with nucleolonemas
      (both supposed to be RNA biosynthetically active) were gradually replaced by ring
      shaped nucleoli and finally by micronucleoli reflecting the reversible and
      irreversible inhibition of RNA synthesis, respectively. The occurrence of the
      main nucleolar types and their values in primitive erythroid cells of the
      developing chick depend not only on the maturation stage of the blood cells, but
      also on the developmental stage of the chick embryo. In comparison with the
      definitive erythroid line of the post-hatching chick and hen, the cells of the
      chick embryonic primitive erythroid line possess relatively high values of
      "active" nucleolar types. These are still present in advanced maturation stages,
      and occur also as definitive erythroid lines of lower vertebrates.

PMID- 7526744
TI  - The cells of the dorsal iris involved in lens regeneration are myoepithelial
      cells whose cytoskeleton changes during cell type conversion.
AB  - During newt lens regeneration, the pigmented epithelial cells (PECs) of the
      dorsal iris dedifferentiate and give rise to a new lens. We have studied the
      cytoskeleton of the PECs using iris flat mounts and sections. In flat-mount iris
      preparations stained by labelled phalloidin three main regions can be recognized:
      the pupillary (P) ring, the middle (M) ring, and the more external junctional (J)
      ring. The cells of the P ring that give rise to the lens have an elongated
      spindle shape and exhibit an elaborate cytoskeleton of actin filament bundles
      oriented along the long axis of the cells, reminiscent of myoepithelial or smooth
      muscle cells. These cells express smooth muscle-specific alpha actin, muscle
      gamma actin and cytokeratin II, and adhere to each other through the cell
      adhesion molecule A-CAM. During dedifferentiation, actin staining increases
      considerably as the actin filament bundles thicken and shorten and then
      accumulate preferentially in the apical and basel regions of the elongating lens
      fibres. Cytokeratin II, which is also organized as fibrils along the long axis of
      the normal iris PECs, increases progressively during dedifferentiation, when it
      is organized as a thick band surrounding the nucleus. The expression of this
      protein is repressed during lens fibre differentiation, but is retained in
      mitotic cells. The data suggest that during cell type conversion some
      cytoskeletal proteins increase and reorganize, while others disappear during lens
      fibre differentiation.

PMID- 7526746
TI  - Effects of short-term high-dose testosterone propionate administration on medium
      molecular-weight proteins of human seminal plasma.
AB  - Effects of short-term high-dose testosterone propionate treatment on medium
      molecular-weight proteins (lactoferrin, albumin, prostatic acid phosphatase,
      prostate specific antigen) and on zinc and fructose levels were investigated in
      the seminal plasma of seven normal volunteers. A significant reduction in levels
      of prostatic-acid phosphatase, zinc and, to a lesser degree, prostate-specific
      antigen, lactoferrin and fructose was observed on the 14th day of androgen
      treatment, concomitantly with the maximal increase in free androgen-circulating
      levels. The data obtained suggest that testosterone administration may induce a
      reduction in the sex accessory-gland secretion. Indeed, this effect tends to
      disappear with withdrawal of hormone treatment. Therefore, the authors suggest a
      close follow-up of prostatic and vesicular function during the long-term high
      dose testosterone intake, used frequently as anabolic treatment by athletes and
      body builders.

PMID- 7526748
TI  - Medium starch, please.

PMID- 7526747
TI  - Inhibitory effects of anesthetics on cyclic guanosine monophosphate (cGMP)
      accumulation in rat cerebellar slices.
AB  - General anesthetics, including halothane, isoflurane, and barbiturates, suppress
      endothelium-dependent formation of 3',5'-cyclic guanosine monophosphate (cGMP) in
      the systemic and cerebral vasculature. The present study was conducted to
      determine whether these anesthetics have similar effects on the nitric oxide (NO)
      cGMP system in the brain, and to elucidate the mechanism responsible. In rat
      cerebellar slices, formation of cGMP was suppressed by halothane after
      stimulation by N-methyl-D-aspartate (NMDA, 0.1 mM) and D-aspartate (1.0 mM) but
      not after stimulation by sodium nitroprusside (SNP, 0.3 mM). Isoflurane (2%)
      suppressed NMDA (0.1 mM)-stimulated, but not D-aspartate (1.0 mM)- and
      nitroprusside (0.3 mM)-stimulated formation of cGMP. In contrast, thiopental (0.1
      1.0 mM) suppressed NMDA (0.1 mM)-, D-aspartate (1.0 mM)-, and nitroprusside (0.3
      mM)-stimulated formation of cGMP. Treatment with aminophylline (0.1 mM), a
      phosphodiesterase inhibitor, did not influence the effect of thiopental,
      suggesting that the effect of thiopental was not mediated by activation of
      phosphodiesterase. D-Aspartate increases intracellular calcium, which in turn
      activates NO synthase, and nitroprusside generates NO without activation of NO
      synthase. Therefore, the present findings strongly suggest that halothane
      inactivates NO synthase (or related cofactors) without marked interaction with
      the NMDA receptor, that isoflurane may interact with the NMDA receptor, receptor
      coupled G-protein, or calcium channels, and that thiopental suppresses guanylate
      cyclase activity.

PMID- 7526749
TI  - Global cerebral ischemia: effects of pentastarch after reperfusion.
AB  - There has been considerable interest in the use of synthetic hydroxyethyl starch
      macromolecules (e.g., pentastarch, a colloid used for intravascular fluid
      replacement) to reduce microvascular permeability and reperfusion injury after
      cerebral ischemia. A recent report found that hemodilution with pentastarch
      reduced brain injury and cerebral edema after temporary focal ischemia. We
      compared the effects of pentastarch versus 0.9% saline on brain edema after
      reperfusion in a model of temporary global ischemia in halothane-anesthetized
      rabbits. To ensure the validity of our model, we studied an additional group of
      animals in which we deliberately raised plasma osmolality with hypertonic saline
      (1.5%) in the expectation of finding a decreased brain water content at the
      conclusion of the experiment. Animals were hemodiluted to a hematocrit of 20%
      with normal saline (control group) (n = 9), pentastarch (n = 7), or hypertonic
      saline (n = 5). After hemodilution, the animals underwent a 25-min period of
      global cerebral ischemia, followed by 180 min of reperfusion. The animals were
      then killed and brain water content was assessed by microgravimetry and by the
      wet-dry weight method. As anticipated, colloid osmotic pressure was maintained in
      the pentastarch group, and plasma osmolality became significantly increased in
      the hypertonic saline group. There were no intergroup differences at any time for
      central venous pressure, mean arterial pressure, intracranial pressure, or PaCO2.
      Brain water content was significantly decreased in the hypertonic saline group.
      No difference in brain water content was detected between the control group and
      the pentastarch group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526750
TI  - Transfer and uptake of alfentanil in the human placenta during in vitro
      perfusion.
AB  - Alfentanil, a short-acting lipophilic opioid, is used for labor analgesia and
      cesarean section and may cause neonatal depression. However, direct placental
      alfentanil transfer has not been studied. We measured placental alfentanil
      transfer and uptake during in vitro perfusion. Placenta lobules from healthy
      parturients were perfused with biophase at pH 7.4, 95%:5% O2:CO2. Maternal to
      fetal (MTF, n = 10) and fetal to maternal (FTM, n = 10) transfer were examined
      during perfusion with alfentanil 10 ng/mL, antipyrine, and creatinine for 1 h.
      Thereafter, both MTF and FTM placentas were assayed for alfentanil content (n =
      3), or perfused with biophase for 1 h to determine drug washout and then assayed
      for alfentanil content (n = 3). After the 1 h washout, the remaining MTF
      placentas (n = 4) were then perfused MTF with high-dose alfentanil 1000 ng/mL to
      assess saturability of placental transfer. The remaining FTM placentas (n = 4)
      were then perfused with alfentanil 10 ng/mL in the MTF direction to verify that
      the same alfentanil transfer characteristics found between placentas were valid
      when the direction of drug transfer was reversed in the same placenta. Alfentanil
      was rapidly transferred (< 5 min) across the placenta both MTF and FTM. During
      MTF transfer, fetal effluent reached a plateau at 2.2 ng/mL between 35 and 55
      min, and was unmeasurable 30 min into washout. During FTM transfer, maternal
      effluent reached a plateau at 1.9 ng/mL at 25-45 min, and was absent after 20-45
      min of washout.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526752
TI  - Lindane toxicity in a 24-year-old woman.
AB  - A case of lindane toxicity in a 24-year-old woman who used lindane shampoo for
      treatment of an alleged case of lice infestation is described. The patient
      experienced uncontrolled motor activity that began approximately 2 hours after
      treatment and resolved approximately 48 hours later. A review of the literature
      revealed that most cases of acute lindane toxicity resulting from topical
      application have occurred in the pediatric and geriatric populations and are
      manifested by grand mal seizures. No case of acute lindane toxicity resulting
      from topical use was found in the emergency medicine literature. This case
      illustrates the toxic, neurologic effects of lindane in a young adult.

PMID- 7526751
TI  - Selective anesthetic inhibition of brain nitric oxide synthase.
AB  - BACKGROUND: It has been postulated that nitric oxide (NO) is a neurotransmitter
      involved in consciousness, analgesia, and anesthesia. Halothane has been shown to
      attenuate NO-mediated cyclic guanosine monophosphate accumulation in neurons, and
      a variety of anesthetic agents attenuate endothelium-mediated vasodilation,
      suggesting an interaction of anesthetic agents and the NO-cyclic guanosine
      monophosphate pathway. However, the exact site of anesthetic inhibitory action in
      this multistep pathway is unclear. The current study examines effects of volatile
      and intravenous anesthetic agents on the enzyme nitric oxide synthase (NOS) in
      brain. METHODS: NOS activity was determined by in vitro conversion of
      [14C]arginine to [14C]citrulline. Wistar rats were decapitated and cerebellum
      quickly harvested and homogenized. Brain extracts were then examined for NOS
      activity in the absence and presence of the volatile anesthetics halothane and
      isoflurane, and the intravenous agents fentanyl, midazolam, ketamine, and
      pentobarbital. Dose-response curves of NOS activity versus anesthetic
      concentration were constructed. Effects of anesthetics on NOS activity were
      evaluated by analysis of variance. RESULTS: Control activities were 57.5 +/- 4.5
      pmol.mg protein-1.min-1 in the volatile anesthetic experiments and 51.5 +/- 6.5
      pmol.mg protein-1.min-1 in the intravenous anesthetic experiments. NOS activity
      was not affected by ketamine (< or = 1 x 10(-4) M), pentobarbital (< or = 5 x 10(
      5) M), fentanyl (< or = 1 x 10(-5) M), and midazolam (< or = 1 x 10(-5) M).
      Halothane decreased NOS activity to 36.7 +/- 2.5 (64% of control, P < 0.01 from
      control), 23.8 +/- 4.3 (41%, P < 0.01 from control and < 0.05 from 0.5%
      halothane), 25.2 +/- 3.8 (44%, P < 0.01 from control and < 0.05 from 0.5%
      halothane), and 19.7 +/- 2.8 (34%, P < 0.01 from control and < 0.05 from 0.5%
      halothane) pmol.mg protein-1.min-1 at 0.5, 1.0, 2.0, and 3.0% vapor. Isoflurane
      decreased NOS activity to 48.9 +/- 6.1 (85% of control), 46.0 +/- 3.2 (80%, P <
      0.05 from control), 40.3 +/- 5.1 (70%, P < 0.05 from control), and 34.2 +/- 4.0
      (60%, P < 0.05 from control and 0.5% and 1.0% isoflurane) pmol.mg protein-1.min-1
      at 0.5, 1.0, 1.5, 2.0% vapor, respectively. CONCLUSIONS: Volatile anesthetics
      inhibit brain NOS activity in an in vitro system, but the intravenous agents
      examined have no effect at clinically relevant concentrations. This inhibition
      suggests a protein-anesthetic interaction between halothane, isoflurane, and NOS.
      In contrast, intravenous agents appear to have no direct effect on NOS activity.
      Whether intravenous agents alter signal transduction or regulatory pathways that
      activate NOS is unknown.

PMID- 7526754
TI  - Substance P and calcitonin gene-related peptide-like immunoreactive nerve fibers
      in lungs from adult equids.
AB  - Distribution of pulmonary nerves immunoreactive for either substance P or
      calcitonin gene-related peptide was determined, using immunohistochemical methods
      on healthy lungs from adult equids. The overall patterns of distribution of
      substance P and calcitonin gene-related peptide-like immunoreactivity were
      similar. Distribution of immunoreactive nerves was not uniform throughout the
      lungs; nerve fibers immunoreactive for these peptides were more frequently
      observed near the hilus of the lung than in the caudal lobes or in the periphery
      of the lung. Nerve fibers immunoreactive for substance P or calcitonin gene
      related peptide were most abundant in the lamina propria of the trachea and
      larger airways, particularly within and directly below the airway epithelium;
      they were also frequently associated with bronchial and pulmonary vessels.
      Presence of nerve fibers immunoreactive for substance P and calcitonin gene
      related peptide in peribronchial neural ganglia indicated that these sensory
      nerves may modulate parasympathetic regulation of pulmonary function. Nerve
      fibers immunoreactive for substance P and calcitonin gene-related peptide were,
      therefore, well placed to detect inhaled agents and to contribute to the
      pulmonary response to irritants and pathogens.

PMID- 7526753
TI  - Association between neutrophil functions and periparturient disorders in cows.
AB  - Neutrophil functions were examined in healthy periparturient dairy cows (n = 46)
      and in cows with retained placenta and metritis complex (n = 20); metritis (n =
      18); or mastitis (n = 13). Blood samples (50 ml) were collected from each cow via
      jugular vein twice weekly from 1.5 weeks before to 4 weeks after parturition.
      Neutrophil function was evaluated, using 6 tests: random migration, chemotaxis,
      ingestion, myeloperoxidase activity (iodination), superoxide production
      (cytochrome C reduction), and antibody-dependent cell-mediated cytotoxicity.
      Ability to ingest bacteria and random migration activity of neutrophils from
      clinically normal cows were high around parturition and increased immediately
      after parturition, whereas myeloperoxidase activity and antibody-dependent cell
      mediated cytotoxicity ability of neutrophils from these cows decreased after
      parturition. Measurement of neutrophil function in 4 ovariectomized cows revealed
      significant (P < 0.0005) seasonal changes in results of all 6 functional assays.
      We observed various defects of neutrophil function in all cows with abnormal
      conditions after parturition. Before parturition, superoxide production activity
      by neutrophils from cows with metritis and chemotaxis by neutrophils from cows
      with mastitis were significantly (P < 0.001 and P < 0.05, respectively) lower,
      indicating that a defect of neutrophil function may be a predisposing factor in
      the development of these disorders. In conclusion, the host defense role of
      neutrophils in periparturient cows was impaired, principally because of a defect
      in killing capacity, which may increase susceptibility to infections. We also
      investigated the in vitro effects of arachidonic acid metabolites and recombinant
      human colony-stimulating factors (rhCSF) on functions of neutrophils from
      clinically normal and postparturient cows with abnormalities, including retained
      placenta, metritis, or mastitis (n = 5/group). Each abnormal cow was matched for
      postpartum period with a clinically normal cow. Neutrophils from individual cows
      were preincubated with arachidonic acid metabolites (prostaglandin F2 alpha, 10(
      7) M; prostaglandin E2, 10(-6) M; leukotriene B4, 10(-8) M; and lipoxin B, 10(-8)
      M) and rhCSF (rh-granulocyte-CSF, 1,000 or 6,000 U/ml; rh-granulocyte-macrophage
      CSF, 5 or 15 ng/ml) in a 37 C water bath for 30 minutes before submitting them to
      function assays. There was no response by neutrophils from either clinically
      normal or abnormal postparturient cows to treatment with either arachidonic acid
      metabolites or rhCSF in any of the 6 functional assays. However, preincubation of
      neutrophils alone in a 37 C water bath for 30 minutes resulted in some alteration
      of neutrophil function.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7526755
TI  - Credentialing physicians for new technology: the physician's learning curve must
      not harm the patient.
AB  - Laparoscopic Cholecystectomy (L.C.) offers advantages that are realized only when
      patient safety is assured. In November 1990, The Department of Surgery at The New
      York Hospital Medical Center of Queens initiated a program to introduce this new
      technology to surgeons who had not performed the operation previously. A
      preceptorship program was initiated, accompanied by contemporaneous quality
      assurance review. This is the experience of 15 general surgeons who performed
      their first 400 L.C.s from November 1990 through March 1993. There were no deaths
      and only one common bile duct injury (0.25%).

PMID- 7526756
TI  - Immunostimulation in sepsis.
AB  - With the purpose of a practical synthesis the Authors consider their personal
      experience and an overview of the international literature on the topic, making a
      point of the actual knowledge on stimulation to treat the sepsis. Therefore their
      study take in account the characteristics of the human immune system and the
      peculiarities of the immunostimulating drugs today at hand, going down to
      practical employment of the last therapeutical applications.

PMID- 7526757
TI  - [Parietal recurrence after resection of colorectal carcinoma].
AB  - The incidence of local recurrence of colo-rectal carcinoma is about 15-50%. The
      parietal recurrence is localized next parietal incision and its incidence is rare
      (0.2-2%). The treatment of this lesion is based on palliative radiotherapy and
      chemotherapy; the surgical treatment is based on parietal resection. The Authors
      describe a case of parietal recurrence after colo-rectal adenocarcinoma and
      conclude that the prognosis of this lesions is infaust.

PMID- 7526758
TI  - Inhibition of tumor angiogenesis.
AB  - The exponential growth of solid tumors depends upon induction of new vessel
      growth, a process mediated by diffusable angiogenic factors produced by tumor
      cells. By inhibiting angiogenesis, it is now possible to modulate tumor growth
      and metastasis in laboratory animals. The first described inhibitor of
      angiogenesis was a protein derived from cartilage. Other important classes of
      antiangiogenic agents include angiostatic steroids combined with heparin or
      heparin derivatives, and the synthetic derivatives of fumigallin. As the
      mechanisms of action of these and other angiostatic agents are being elucidated,
      it is becoming apparent that many modulators of collagen metabolism inhibit
      angiogenesis and may offer clinically useful anticancer treatments. Minocycline
      and other tetracycline derivatives with anticollagenase properties have been
      shown to be potent inhibitors of angiogenesis. These agents, when administered
      with other standard cancer therapies, help prolong survival in laboratory animals
      with solid tumors. Further studies of these biologic response modifiers of tumor
      progression are under way in the hope that they will offer effective new
      treatments for cancer in humans.

PMID- 7526759
TI  - Inhibition of angiogenesis by anthracyclines and titanocene dichloride.
AB  - The anthracycline antibiotics, daunorubicin, doxorubicin, and epirubicin, which
      are widely used for treatment of malignancies, have been evaluated for their
      effect on angiogenesis in relation to the inhibition of collagenase type IV
      reported previously. In the chick chorioallantoic membrane (CAM) system of
      angiogenesis, anthracyclines inhibited vascular density at doses of 5-20
      micrograms/disc as well as collagenous protein biosynthesis, which is a reliable
      index of angiogenesis. Similarly, all three anthracyclines inhibited tube
      formation in the in vitro system of angiogenesis using human umbilical vein
      endothelial cells (HUVECs) plated on Matrigel. The inhibition was dose-dependent
      and caused 50% inhibition at concentrations of 2.5-15 micrograms/mL. At
      concentrations of anthracyclines which prevented tube formation and angiogenesis,
      there were no cytotoxic effects, as evidenced by methylene blue uptake, and the
      growth of these endothelial cells was not inhibited. The experimental antitumor
      agent titanocene dichloride inhibited collagenase type IV from Walker 256
      carcinosarcoma with IC50 approximately 0.2 mM. Titanocene also prevented
      angiogenesis in the CAM and tube formation by HUVECs on Matrigel at
      concentrations that were without effect on growth or cytotoxicity of endothelial
      cells or Walker 256 cells in culture. The antiangiogenic effect of the
      aforementioned antitumor agents at therapeutically attainable concentrations may
      explain, at least in part, their antitumor properties because angiogenesis is an
      essential process for tumor growth and metastasis. The antiangiogenic effect is,
      however, unrelated to metalloproteinase inhibition because higher concentrations
      are required for that effect than for inhibition of angiogenesis.

PMID- 7526760
TI  - Interaction of alpha 2-macroglobulin with matrix metalloproteinases and its use
      for identification of their active forms.

PMID- 7526762
TI  - Inhibition of cartilage metalloproteoglycanases and stromelysin by anionic
      homopolymers.

PMID- 7526761
TI  - Treatment of canine osteoarthritis with sodium pentosan polysulfate and insulin
      like growth factor-1.

PMID- 7526764
TI  - Nitric oxide/cyclic GMP-mediated signal transduction.

PMID- 7526763
TI  - A possible role for MMP-2 and MMP-9 in the migration of primate arterial smooth
      muscle cells through native matrix.

PMID- 7526766
TI  - Parathyroid hormone and parathyroid hormone-related protein stimulate adenylate
      cyclase in human endometrial stromal cells.

PMID- 7526765
TI  - Enterochromaffin-like cell pathobiology of mastomys.

PMID- 7526768
TI  - Ciliogenesis and mucus synthesis in cultured human respiratory epithelial cells.
AB  - The mechanisms for the regulation of ciliogenesis and for the synthesis of mucus
      are not well understood. We sought to develop a culture system for
      differentiating ciliated and secretory types of human respiratory epithelial
      (HRE) cells. Dissociated HRE cells obtained from nasal polyps and maxillary sinus
      mucosa were cultured on type I collagen gel. Cells grown to confluence on
      collagen gel lost their cilia and exhibited a flat, squamous-like appearance.
      After reaching confluence, the cultured cells with a collagen gel substrate were
      removed from plastic dishes and floated in the culture medium. After 7 days in
      the floating culture, some cells exhibited several centrioles or basal bodies,
      while others showed secretory granules. The secretory phenotype predominated
      after 7 days. After 14 days in the floating culture, nearly all cells were
      ciliated. The results demonstrate that the differentiation of HRE cells can be
      induced by floating cultured cells with a collagen gel substrate in a defined
      culture medium.

PMID- 7526767
TI  - Growth factors and decidualization in vitro.
AB  - Growth factors are believed to act as local regulators of endometrial cyclic
      activity, but there is limited information on their regulation of decidual
      differentiation and function. Cell cultures of human endometrial stroma treated
      with progesterone (P) undergo morphologic, proliferative and secretory changes
      characteristic of decidualizing endometrium. In the presence of P, different
      growth factors can stimulate cell proliferation, but decidual differentiation is
      induced specifically by EGF, as shown by the production of prolactin (PRL),
      fibronectin, laminin, and insulin-like growth factor binding protein 1 (IGFBP-1).
      The present study investigates the effects of the insulin-like growth factors
      (IGF-I, IGF-II) on decidualization in vitro, as indicated by a P-dependent growth
      response and by the secretion of PRL and IGFBP-1. IGFs were required together
      with EGF and P to stimulate stromal cell proliferation. In contrast, PRL (38 +/-
      4 ng/day/10(6) cells) and IGFBP-1 (26 +/- 3 micrograms/day/10(6) cells) were
      secreted by in vitro decidualized cells in the absence of exogenous IGFs.
      However, IGFs regulated both IGFBP-1 and PRL secretion in a dose-dependent
      biphasic manner. Stimulation of IGFBP-1 (200-250%) and PRL (243-324%) peaked at 1
      ng/ml for IGF-I, and 10 ng/ml for IGF-II, followed by inhibition at higher
      peptide concentrations (ED50s 3 and 30 ng/ml, respectively). Maximal
      physiological doses (100 ng/ml) of IGF-I and IGF-II virtually abolished IGFBP-1
      secretion (1% and 2% of basal levels, respectively), but did not cause total
      suppression of PRL secretion (8% and 22% of basal levels). IGF-induced
      mitogenesis was inversely correlated with endogenous IGFBP-1 levels in in vitro
      decidualized stromal cultures. Our studies show that growth factor interactions
      regulate decidual function, and that specific cellular functions associated with
      the decidual response are differentially regulated by growth factor interactions.
      Our findings support a role for the IGF system in autocrine/paracrine
      interactions during decidualization and early pregnancy. It is speculated that
      IGF-II may constitute one of the embryonic signaling mechanisms during early
      postimplantation stages.

PMID- 7526769
TI  - Fresh haemolysis interferes with blocked p-nitrophenylmaltoheptaoside amylase
      methods.
AB  - Two commercial amylase methods which employ p-nitrophenol derivatives of blocked
      maltoheptaosides suffer from negative interference due to fresh haemolysate.
      Specimen storage at room temperature, or pre-incubation at 37 degrees C or 57
      degrees C removes the effect. Incubation of amylase reagent at 37 degrees C with
      fresh haemolysate where the final haemoglobin concentration was 0.011 g/L, showed
      a rapid fall in absorption around 414 nm which became stable after 150 min. Since
      p-nitrophenol, the product of the amylase reaction, is measured at 405 nm it is
      concluded that the negative interference from fresh haemolysis is due to the
      transitory fall in absorption around 405 nm. It is recommended that amylase
      measurements using this technique, particularly those performed as an emergency,
      should not be done on haemolysed specimens.

PMID- 7526770
TI  - Establishment and characterization of human vaginal malignant melanoma
      xenotransplants.
AB  - Human vaginal malignant melanoma represents rare gynecological malignancies of
      poor prognosis. We have established a melanoma tumor line in nude mice,
      designated Mela-1, and have examined the histological and biological
      characteristics of this tumor. The Mela-1 tumor has preserved the histological,
      histochemical and biological characteristics of malignant melanoma even after 20
      passages. Tumor cells are of epitheloid shape varying in size. An ultrastructural
      study revealed that the tumor cells were characterized by the presence of cells
      with deeply indented nuclei, and both types of melanosomes, eumelanosomes and
      pheomelanosomes, in various stages of maturation with vesiculo-globular bodies in
      the cytoplasm. Melanin analysis of the tumor indicated the Mela-1 tumor to be
      pheomelanic. Immunohistochemical examinations revealed that the Mela-1 cells were
      stained positively by melanoma-associated antibody (NKI/C3) and by antibodies for
      S-100 protein and vimentin, and negatively for keratin and CEA. The levels of
      AFP, CA125 and CEA in sera of tumor-bearing mice were within normal range. The 5
      S-cysteinyldopa level in sera of tumor-bearing mice correlated well with the size
      of the tumor. Chromosomal analysis showed the human karyotype with great
      heterogeneity and a modal number of 102 chromosomes. Thus the Mela-1 tumor will
      be useful in establishing the biological characteristics in the search for an
      effective treatment of human malignant melanoma of the vagina.

PMID- 7526772
TI  - The diagnostic and therapeutic window for localized carcinoma of the prostate.
AB  - The natural history of prostate cancer has been regarded as unpredictable for a
      long period of time. The discrepancy between histologically identifiable (40%)
      and clinically diagnosed carcinomas (8%) led to the term of "latent" prostate
      cancer and to a considerable diagnostic and therapeutic dilemma. Based on
      previous studies showing that biological aggressiveness of prostate cancer is a
      direct function of tumor volume and that tumor volume and serum-PSA are
      proportional, two basically different groups of patients were evaluated. The
      first group consisted of 43 patients with untreated carcinomas of the prostate
      followed with serial PSA determinations. The exponential (log-linear) rise in PSA
      led to the conclusion of an exponential tumor growth rate. The median doubling
      time of clinically organ-confined tumors was 4 years and became shorter with
      higher clinical stages and poorly differentiated histological grades. The second
      group consisted of 139 patients who underwent cystoprostatectomy for bladder
      cancer and had no evidence for simultaneously identifiable prostate cancer. In 55
      patients (40%) unsuspected prostate cancer was found in the specimen; the volume
      distribution of these carcinomas was exponential. Eleven of the 139 men (7.9%)
      had a prostate cancer greater than 0.5 cc, corresponding to the 8% risk for a man
      being diagnosed within his life-time with a clinically significant carcinoma of
      the prostate. In conclusion, the other 44 carcinomas below 0.5 cc may never reach
      clinical significance due to their small size and their long doubling time; in
      this sense they can be considered "latent".(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526771
TI  - Correlation between immunohistochemical patterns and serum levels of PSA and PSAP
      in prostatic pathology: evaluation of 198 prostatic fine needle biopsies.
AB  - PSA and PSAP were examined in 198 prostatic biopsies and correlated with PSA and
      PSAP serum levels evaluated before biopsies. In every type of lesion there was no
      relation between PSA or PSAP serum levels and their expression in biopsy
      specimens. PSA and PSAP staining was similar in both cancer and benign
      hyperplasia and lower in dysplasia, atrophy and prostatitis; while serum levels
      were higher in adenocarcinomas than in other lesions. A significant difference of
      PSAP serum levels was noted in different Gleason's grading of neoplasia, found
      neither with PSA serum levels/nor with PSA and PSAP tissue staining.

PMID- 7526774
TI  - The shoulder-hand syndrome after stroke: a prospective clinical trial.
AB  - Shoulder-hand syndrome developed in 36 (27%) of 132 hemiplegic patients in a
      prospective study. Subluxation, paresis of the shoulder girdle, moderate
      spasticity, and deficits in confrontation visual field testing were the major
      risk factors. In a placebo-controlled, nonblinded trial, 31 of the 36 patients
      became almost symptom free within 10 days' treatment with low doses of oral
      corticosteroids. Shoulder joint capsules taken at autopsy of 7 patients showed
      signs of previous trauma of the affected shoulder. In the second part of this
      study on another 86 patients, early awareness of potential injuries to shoulder
      joint structures reduced the frequency of shoulder-hand syndrome from 27 to 8%.
      These clinical findings suggest that shoulder-hand syndrome in hemiplegia is
      initiated by peripheral lesions. A self-perpetuating vicious cycle may be
      established, followed by the clinical picture of a "reflex sympathetic
      dystrophy." In the majority of stroke patients, this clinical phenomenon seems to
      be preventable by avoiding shoulder trauma.

PMID- 7526775
TI  - Myelin basic protein peptide specificity and T-cell receptor gene usage of HPRT
      mutant T-cell clones in patients with multiple sclerosis.
AB  - Characterization of T cells responding to autoantigens is central to
      understanding autoimmune disease. We have used somatic mutation at the
      hypoxanthine guanine phosphoribosyltransferase (HPRT) gene as an index of T-cell
      amplification in vivo. With this strategy we previously showed that myelin basic
      protein-reactive T cells can be isolated only from the HPRT mutant T-cell
      population cultured from the peripheral blood of multiple sclerosis patients and
      not from normal individuals. In this study, 165 HPRT mutant and 104 wild-type
      clones were examined for their reactivity to myelin basic protein and overlapping
      peptides of myelin basic protein. Five HPRT mutant clones that recognized myelin
      basic protein and myelin basic protein peptides along with three clones that
      responded to myelin basic protein peptide alone were isolated. All but one of the
      eight clones recognized peptides derived from the carboxy terminus of myelin
      basic protein (p84-168). Sequence analysis showed heterogeneous expression of T
      cell receptor V alpha and V beta genes and CDR3s. These studies showed that in
      vivo amplified autoimmune T cells from patients with long-standing disease use
      diverse T-cell receptor elements in the recognition of C-terminal myelin basic
      protein peptides.

PMID- 7526773
TI  - [PSA: a new prostatic marker. A help or an added factor of confusion?].
AB  - In patients with a normal digital rectal examination and serum PSA levels under
      18.4 ng/ml Yang (i.e. under 10.0 ng/ml Hybritech or under 14.4 ng.ml with the
      Basel Cantonal Hospital assay), twice yearly then yearly follow-up examinations
      are sufficient. More closely spaced examinations and a transrectal ultrasound
      scan are appropriate in patients with abnormalities upon digital rectal
      examination, especially when serum PSA levels are consistently elevated.

PMID- 7526777
TI  - Molecular mimicry between GQ1b ganglioside and lipopolysaccharides of
      Campylobacter jejuni isolated from patients with Fisher's syndrome.
AB  - We isolated Campylobacter jejuni from 2 patients with Fisher's syndrome
      subsequent to enteritis. Crude lipopolysaccharide fractions were extracted from
      the bacteria and separated by thin-layer chromatography. Monoclonal antibodies to
      GQ1b ganglioside (GMR13 and 7F5) reacted with both lipopolysaccharide fractions,
      indicating that the lipopolysaccharides bear the GQ1b epitope. This is the first
      report of molecular mimicry between neural tissue components and the antecedent
      infectious agents of Fisher's syndrome.

PMID- 7526776
TI  - Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis
      brains.
AB  - The amount of messenger RNA encoding human inducible nitric oxide synthase and
      the presence and distribution of NADPH diaphorase were determined in tissue
      sections from multiple sclerosis (MS) and control brains. Levels of human nitric
      oxide synthase messenger RNA were markedly elevated in MS brains when compared to
      normal control brains. NADPH diaphorase activity, a histochemical stain
      reflecting nitric oxide synthase catalytic activity, was detected in reactive
      astrocytes in active demyelinating MS lesions and at the edge of chronic active
      demyelinating lesions. Control brains did not contain NADPH diaphorase-positive
      astrocytes. These results implicate the free radical nitric oxide in the
      pathogenesis of demyelinating MS lesions.

PMID- 7526778
TI  - The retroviral enzymes.
AB  - We have reviewed the current state of knowledge concerning the three enzymes
      common to all retroviruses. It is informative to consider them together, since
      their activities are interrelated. The enzymatic activities of RT and IN depend
      on processing of polyprotein precursors by PR. Furthermore, RT produces the viral
      DNA substrate to be acted upon by IN. All three of these retroviral enzymes
      function as multimers, and it is conceivable that specific polyprotein precursor
      interactions facilitate the multimerization of all of them. The multimeric
      structures of the enzymes are, however, quite different. PR is a symmetric
      homodimer whose subunits contribute to formation of a single active site. RT (of
      HIV, at least) is an asymmetric heterodimer in which one subunit appears to
      contribute all of the catalytic activity and the second is catalytically
      inactive, but structurally important. IN also functions minimally as a dimer for
      processing and joining. The retroviral enzymes represent important targets for
      antiviral therapy. Considerable effort continues to be focused on developing PR
      and RT inhibitors. As more is learned about IN, such efforts can be extended.
      Since these enzymes are critical at different stages in the retroviral life
      cycle, one optimistic hope is that a combination of drugs that target all of them
      may be maximally effective as therapy for AIDS.

PMID- 7526779
TI  - Nitric oxide: a physiologic messenger molecule.

PMID- 7526780
TI  - Function and structure relationships in DNA polymerases.

PMID- 7526781
TI  - Differential antiviral activities and intracellular metabolism of 3'-azido-3'
      deoxythymidine and 2',3'-dideoxyinosine in human cells.
AB  - Dideoxynucleosides such as 3'-azido-3'-deoxythymidine (AZT) and 2',3'
      dideoxyinosine (ddI) can effectively inhibit the replication of human
      immunodeficiency virus (HIV) in T lymphoid cells. There is evidence that HIV can
      infect and replicate in other cells including monocytoid cells and macrophages.
      The present study compared the antiretroviral activities of ddI and AZT in three
      lineages of human cells, i.e., MOLT4 (T lymphocytoid, CD4+), U937 (monocytoid,
      CD4+), and HT1080 (fibroblastoid, CD4-) cells. Feline leukemia virus, a
      retrovirus that causes immunodeficiency in cats, was used to infect the cells.
      The drug concentrations needed to reduce the viral p27 antigen titers in cell
      lysates by 50% (IC50s) were determined. The data show that AZT and ddI inhibited
      viral replication in all three cell lines. The IC50s of AZT were 0.02, 1.75, and
      2.31 microM in MOLT4, HT1080, and U937 cells, respectively. For ddI, the IC50s
      were 4.31, 9.52, and 43.5 microM, respectively. These data indicate differential
      antiviral activities of ddI and AZT in the different cells with the following
      rank order of drug sensitivity: MOLT4 > HT1080 > U937. A study of the
      intracellular metabolism of [3H]AZT and [3H]ddI shows that the antiretroviral
      activities of AZT and ddI in the three cell lines correlated with the levels of
      their intracellular triphosphate metabolites.

PMID- 7526784
TI  - Inhibition of protein synthesis occurring on tetracycline-resistant, TetM
      protected ribosomes by a novel class of tetracyclines, the glycylcyclines.
AB  - One of the two major mechanisms of tetracycline resistance is ribosomal
      protection. Of this resistance type, tet(M) is the best characterized. Although
      the mechanism of tet(M) resistance has not yet been fully elucidated, it has been
      demonstrated that ribosomes isolated from a tet(M) strain are resistant to
      inhibition of protein synthesis by tetracycline. A new generation of tetracycline
      compounds, the glycylcyclines, that are able to inhibit protein synthesis
      occurring on tetracycline-resistant, TetM-protected ribosomes, as well as wild
      type, tetracycline-sensitive ribosomes, have been identified.

PMID- 7526785
TI  - Pharmacology and side-effects of interferons.
AB  - The distribution, catabolic sites and turnover of interferons are reviewed in
      order firstly to improve their utilization, secondly to reduce toxicity and
      thirdly to evaluate alternative routes of administration. In fact catabolic
      pathways are now seen as a salutary system capable in most cases to reduce
      toxicity to an acceptable level.

PMID- 7526783
TI  - Potentiation of bleomycin cytotoxicity in Saccharomyces cerevisiae.
AB  - Lesions introduced into cellular DNAs prelabeled with [2-14C]thymidine or [6
      3H]thymidine, as well as cell killing, were inhibited by the presence of EDTA
      during 20-min reactions of Saccharomyces cerevisiae cells with the low-molecular
      weight bleomycin family of anticancer antibiotics. In contrast, the level of
      killing by low concentrations of bleomycin was higher among cells which had grown
      for three generations in defined synthetic complete medium supplemented with
      ferrous sulfate than among cells grown without iron supplementation. In S.
      cerevisiae, the uptake of iron is facilitated by a plasma membrane ferric
      reductase activity and a high-affinity (Km = 5 x 10(-6) M) ferrous uptake system.
      Lethal effects of 1.3 x 10(-6) M bleomycin increased approximately 50% with 10(
      5) M Fe(II), nearly twofold with 10(-4) M Fe(II), and 2.8 times with 10(-3) M
      Fe(II). Thus, iron preloading is a new experimental approach to increasing and
      studying the effects of the glycopeptides on cellular DNAs and other cellular
      targets. This approach could also be used for studying and better understanding
      DNA repair genes and could serve as a model for studies of redox active chemicals
      in biological systems.

PMID- 7526782
TI  - 5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83), a selective anti-human
      immunodeficiency virus agent with an improved metabolic and toxicological
      profile.
AB  - 5-Chloro-2',3'-dideoxy-3'-fluorouridine (935U83) is a selective anti-human
      immunodeficiency virus (HIV) agent. When tested in phytohemagglutinin-stimulated
      normal human peripheral blood lymphocytes against fresh clinical isolates of HIV
      type 1 (HIV-1) obtained from patients naive to AZT (3'-azido-3'-deoxythymidine
      [zidovudine]), 935U83 inhibited virus growth with an average 50% inhibitory
      concentration (IC50) of 1.8 microM; corresponding IC50s were 0.10 microM for FLT
      (3'-deoxy-3'-fluorothymidine) and 0.23, 0.49, and 0.03 microM for the approved
      agents AZT, ddI (2',3'-dideoxyinosine), and ddC (2',3'-dideoxycytosine),
      respectively. Importantly, 935U83 retained activity against HIV strains that were
      resistant to AZT, ddI, or ddC. Of additional interest, we were unable to generate
      virus which was resistant to 935U83 by passaging either HXB2 (AZT-sensitive) or
      RTMC (AZT-resistant) strains in the presence of high concentrations of 935U83.
      The anabolic profile of 935U83 was similar to that of AZT, and 935U83
      triphosphate was a potent inhibitor of HIV-1 reverse transcriptase.
      Pharmacokinetic evaluation showed good oral bioavailability (86% in mice and 60%
      in monkeys) and less extensive metabolism to the glucuronide relative to AZT.
      935U83 showed low toxicity. In an in vitro assay for toxicity to a human
      erythrocyte progenitor, erythroid burst-forming unit (BFU-E), the IC50 for 935U83
      (> 400 microM) was more than 1,000-fold those of FLT (0.07 microM) and AZT (0.30
      microM). Mild reversible reductions in erythrocytes and associated parameters
      were seen in mice dosed orally with 2,000 mg of 935U83 per kg per day for 1 and 6
      months. In monkeys dosed orally with up to 700 mg/kg/day for 1 and 6 months, the
      only possible treatment-related finding was cataracts in 1 of 12 animals given
      the intermediate dose of 225 mg/kg/day. At the highest doses in mice and monkeys,
      maximal concentrations in plasma were more than 100-fold the anti-HIV IC50s
      against clinical isolates. This safety profile in animals compares very favorably
      with that of any of the anti-HIV drugs approved to date and has led us to begin
      evaluation of 935U83 in patients with HIV infection.

PMID- 7526786
TI  - HBV and HDV replication in experimental models: effect of interferon.
AB  - The use of HBV and HDV experimental models has significantly contributed to
      understand the viral life cycle and to systematically test antiviral effects of
      various drugs on a pre-clinical level. Similar replication strategies of related
      hepadna viruses permit the use of chimpanzees (Pan troglodytes), woodchucks
      (Marmota monax), ground and tree squirrels (Spermophilus beecheyi) or Pekin ducks
      (Anas domesticus) as appropriate animal models. Cell culture systems for in vitro
      infection or transfection using both primary cultures of human and non-human
      hepatocytes and non-hepatocytes and cell lines have recently been identified. The
      advantages and restrictions of these experimental models with respect to
      evaluation of interferon effects on viral and hepatocellular gene expression are
      discussed.

PMID- 7526787
TI  - Effects of hepatitis B and hepatitis C virus replication on the actions of
      interferon.
AB  - Many patients chronically infected with hepatitis B or C do not respond to
      interferon therapy. For hepatitis B infections it is now clear that a viral
      factor down regulates the cells ability to respond to interferon and hence
      prevents effective therapy in some patients. In chronic hepatitis C infections,
      interferon therapy leads to the selection of interferon-resistant viral strains,
      but the mechanism of this resistance is not yet known.

PMID- 7526788
TI  - Interferon in chronic hepatitis B.
AB  - In patients with typical chronic hepatitis B (HBsAg, HBeAg, HBV-DNA-positive),
      treatment with interferon-alpha must be carried out for 4-6 months on an
      alternate-day basis and dosage should be not less than 5 million units/square
      meter of body surface. The therapeutic response (i.e., clearance of replicative
      markers, transaminases normalization, histologic improvement) is achieved in
      about 40% of treated patients and the long-term beneficial effect is maintained
      in about 90% of them. Oriental HBV carriers, children, immunodeficient and highly
      viraemic patients are less likely to respond. Patients given combinations therapy
      (with steroids, antivirals, stimulators of the immune system) do not appear to
      gain more benefit from the association in comparison with treatment with
      interferon alone. Side-effects are usually minor (flu-like symptoms), but in a
      minority major adverse events have also been reported. In conclusion, interferon
      alpha is effective in inhibiting viral replication but new therapeutic regimens
      and a better selection of patients are needed in order to induce persistent
      remissions and to reduce the cost benefit ratio.

PMID- 7526789
TI  - Interferon therapy for the anti-HBe positive form of chronic hepatitis B.
AB  - Two distinct serologic types of chronic hepatitis B have been identified, namely
      the "classical" HBeAg positive form and the "atypical" HBeAg negative, anti-HBe
      positive variant which is due to infection by a mutant HBV having a pre-core stop
      codon that makes the virus unable to produce HBeAg. The anti-HBe positive form is
      currently the prevalent type of chronic hepatitis B in the Mediterranean area,
      being associated with a more severe clinical course compared to HBeAg positive
      cases. The response to interferon therapy in patients with anti-HBe positive
      chronic hepatitis B has been recently investigated in control trials. These
      studies have shown that normalization of ALT with efficient suppression of virus
      activity can be achieved in 50-80% of patients while treated with interferon
      alpha indicating that also the pre-core mutant of HBV is sensitive to the
      antiviral effect of interferon. However, reactivation of hepatitis occurs in a
      variable percentage of initial responders when interferon is stopped. The
      probability of reactivation increases when the disease is of long duration, when
      cirrhosis is present and particularly if the pre-core mutant of HBV has become
      the predominant type of circulating virus, indicating that this HBV variant is
      more resistant to immunoclearance compared to wild type HBV.

PMID- 7526791
TI  - Interferons in human papillomavirus infections.
AB  - Human papillomavirus (HPV) infections usually present as benign warts (e.g.,
      condyloma acuminatum, CA) but can also be responsible for dysplasia and
      carcinoma. Therapeutic options include chemotherapeutic agents, cryotherapy and
      surgery, but all these treatments are anti-tumor, not anti-viral. Interferons
      (IFNs) are the only anti-viral drugs approved for the therapy of benign HPV
      related lesions. While IFN-alpha, IFN-beta and IFN-gamma have all been tested
      against CA, most information is available on IFN-alpha which appears efficacious
      via a number of routes of administration, schedules and dosages with an
      acceptable safety profile. The highest rate of success with IFN-alpha therapy, in
      terms of reduced recurrence rates of CA was reported from studies in which all
      visible lesions were surgically removed with subsequent administration of
      subcutaneous local IFN-alpha. Less data is available on the efficacy of IFNs in
      the treatment of HPV-related dysplasia and carcinoma, but combination therapy
      (e.g., IFN-alpha plus retinoids for cervical carcinoma) appears promising. Future
      advances in control of HPV-related lesions are expected to continue to involve
      IFN combined with non-antiviral therapies as well as the use of exogenous
      inducers of IFNs and other cytokines.

PMID- 7526790
TI  - HPV replication in experimental models: effects of interferon.
AB  - Preclinical evaluation of the effectiveness of interferon (IFN) therapy on human
      papillomaviruses (HPV) has been hampered by the inability to propagate these
      viruses in cell culture. Nonetheless, interferon is used extensively in the
      treatment of HPV infections. Alpha interferons in particular have found a place
      in the treatment of anogenital disease, plantar warts, and laryngeal papillomas.
      While their is significant clinical evidence to suggest that interferon is useful
      in therapy of disease, the cellular mechanism(s) (i.e., antiviral,
      antiproliferative, immunomodulatory) by which IFN is able to control HPV-induced
      pathology is not well understood. This review focuses on experimental animal and
      cell culture models which are currently being used to help identify the
      antiviral, antiproliferative and immunomodulatory effects of IFN on HPV
      infection.

PMID- 7526792
TI  - Multiple effects of interferon on the replication of human immunodeficiency virus
      type 1.
AB  - In this review, I shall summarize the major findings about the effect of IFN on
      the replication of HIV-1 virus in model systems in vitro and will describe the
      known molecular mechanisms involved in the IFN-mediated inhibition of HIV-1
      replication. Finally, I shall relate these findings to the unique features of the
      HIV-1 replication cycle.

PMID- 7526793
TI  - Interferons in the pathogenesis and treatment of human immunodeficiency virus
      infection.
AB  - There still remains several unanswered questions concerning the pathogenesis of
      human immunodeficiency virus (HIV) infection. Interferons (IFNs), as well as
      other cytokines, are both dysregulated in HIV infection and serve as effector
      molecules that modulate the replicative capacity of HIV. Acid-labile IFN-alpha,
      an aberrant form of interferon earlier described in certain autoimmune diseases,
      has been detected in HIV-infected individuals. Conversely, a deficient expression
      of IFN-alpha may occur usually associated with HIV disease. Although conflicting
      findings have been reported on whether IFN-gamma, a product of activated T and
      natural killer (NK) cells, is elevated in the peripheral blood (PB) compartment,
      high levels of its expression have been observed in the germinal centers of the
      lymph nodes during HIV disease. IFN-alpha and IFN-beta have shown potent anti
      retroviral effects in several in vitro systems of both acute and chronic HIV
      infection. These findings have served as the basis of the rationale for their
      therapeutic application, resulting in some positive effects at least in those
      patients with relatively high CD4+ T cell counts and healthy immune functions.
      Furthermore, IFN-alpha has shown important therapeutic effects on HIV-associated
      Kaposi's sarcoma (KS). Both suppressive and inductive effects on HIV replication
      in vitro have been described for IFN-gamma, whereas no clear clinical benefits
      have been reported following its administration to HIV-infected individuals. In
      conclusion, IFNs are involved in several pathogenic aspects of HIV infection and
      AIDS, and certain IFNs may serve as important tools to limit the spread of the
      virus and the progression of disease.

PMID- 7526794
TI  - Development of neutralizing and binding antibodies to interferon (IFN) in
      patients undergoing IFN therapy.
AB  - Since the 1970's, people started to use interferon as a therapeutic agent against
      infectious and neoplastic diseases. Since the beginning of its therapeutical use,
      it was demonstrated that some patients produce, when treated with interferon,
      antibodies able to neutralize its biological activity. This paper will review and
      discuss what it is currently known about the technical, biological, and clinical
      aspects of these antibodies.

PMID- 7526795
TI  - Prospectives on the treatment of chronic hepatitis B and chronic hepatitis C with
      thymic peptides and antiviral agents.
AB  - At the present time, interferon is considered the only effective therapeutic
      approach in the treatment of both chronic hepatitis B and chronic hepatitis C. It
      is clear that the disappointing response rates in both chronic hepatitis B and C
      place added emphasis on efforts to identify alternative forms of therapy. In
      addition to the development of other antiviral agents including the nucleoside
      analogs which might prove more effective and have fewer associated side-effects,
      other agents currently under investigation include thymic peptides such as
      thymosin alpha 1. In the future, the therapeutic approach to the treatment of
      chronic hepatitis B and C may consist of combination therapy using perhaps an
      immune modulator and an antiviral agent or, several antiviral drugs.
      Alternatively, there is indication that cellular targeting systems with delivery
      of the toxic material to the specific cell containing the virus may be more
      effective, while minimizing side-effects. Finally, there are agents such as
      ursodeoxycholic acid which perhaps, makes bile less toxic and can be used as
      adjunctive therapy with improvement in liver chemistry values. The treatment of
      chronic hepatitis B and chronic hepatitis C has shifted in emphasis form the
      concept of treating liver disease towards that of treating viral infections which
      happen to effect primarily the liver.

PMID- 7526798
TI  - Presenting research: effective paper presentations and impressive poster
      presentations.

PMID- 7526797
TI  - Intraspecific metabolic diversity among strains of Burkholderia cepacia isolated
      from decayed onions, soils, and the clinical environment.
AB  - A collection of 218 strains of Burkholderia cepacia (including 18% strain
      replicates) was assembled from organic soils, decayed onions, and clinical
      sources. Each strain was characterized for virulence to onion, catabolic ability
      using the Biolog GN microtiter plate, and several other behaviors. Overall test
      reproducibility was estimated at 98%. The results obtained using the Biolog GN
      system corresponded well to those obtained using standard methods. Three
      coefficients of resemblance (Gower similarity, pattern difference, and Jaccard
      similarity) were calculated and clustered by the group-average method. The sorted
      matrices and phenograms, while giving evidence of an underlying phenetic
      structure to the B. cepacia nomenspecies, gave little evidence of sorting by
      broad source of isolation. Strains isolated from within fields or samples were
      frequently found to be similar, however, strains isolated from fields with
      similar cropping histories were not. The Gower-transformed centroids of ordained
      clusters were projected in a principal coordinate system and estimates of
      disjunction were calculated. Strains of B. cepacia were shown to be non-uniformly
      distributed in taxonomic space. Strains isolated by serial dilution on onion
      slices formed a tight phenetic cluster which includes the type strain of the
      nomenspecies and that of a synonymous group (Pseudomonas multivorans); the
      strains in this phenon were generally virulent to onion and were partially
      differentiated from others by pectolytic behavior and by the production of
      diffusible pigment on King's medium A. Further characterization should better
      resolve the taxonomy of the nomenspecies.

PMID- 7526796
TI  - The interferons: a biological system with therapeutic potential in viral
      infections.
AB  - Successful medical use of interferon for chronic viral infections is increasingly
      dependent on understanding the biologic and molecular mechanisms of the
      interferon system. Interferon (IFN) is one of the body's natural defenses.
      Production of IFN is a defensive response to foreign components of microbes,
      tumors and antigens. This IFN response begins with the production of the IFN
      proteins (alpha, beta and gamma) which then induce antiviral, antimicrobial,
      antitumor, and immunomodulatory actions. Thus, the initial production or
      administration of IFN(s) does not protect directly but instead reacts with
      specific receptors on cell surfaces to activate cytoplasmic transduction signals
      that then enter the nucleus to stimulate cellular genes encoding a number of
      effector proteins which lead to the defensive actions. The known molecular,
      humoral and cellular mechanisms by which these effector proteins exert their
      antiviral activities are presented. In addition, the pathogenesis of chronic
      infections is overviewed in the context of the interferon defenses.

PMID- 7526799
TI  - The inhibition of the constitutive bovine endothelial nitric oxide synthase by
      imidazole and indazole agents.
AB  - Citrulline formation by the Ca2+ CaM-dependent nitric oxide synthase of bovine
      endothelium is inhibited reversibly by 7-nitroindazole, 1-phenylimidazole, and
      imidazole. As measured at 0.67 microM (6R)-5,6,7,8-tetrahydrobiopterin (BH4),
      IC50 values of 0.8, 200, and 50 microM were determined for 7-nitroindazole, 1
      phenylimidazole, and imidazole, respectively. Increasing concentrations of added
      BH4 cofactor increased the IC50 values for 7-nitroindazole and 1-phenylimidazole
      but did not alter the IC50 value for imidazole. 7-nitroindazole inhibited
      citrulline formation by the endothelial cNOS noncompetitively versus arginine
      substrate but competitively versus BH4 with a Ki value of 0.8 microM. 1
      Phenylimidazole inhibited citrulline formation by the endothelial cNOS
      competitively versus both arginine substrate and BH4 with a Ki value of 50
      microM. Imidazole inhibited citrulline formation competitively versus arginine
      substrate but noncompetitively versus BH4 with a Ki value of 50 microM. Neither 7
      nitroindazole, 1-phenylimidazole, nor imidazole inhibited the cytochrome c
      reductase activity of endothelial cNOS at concentrations up to 5000-fold higher
      than their Ki values for inhibition of citrulline formation. By comparison with
      the previously determined kinetic properties of the other nitric oxide synthase
      isoforms, these observations establish that 1-phenylimidazole displays marked
      specificity for inhibiting the inducible nitric oxide synthase isoform and, since
      7-nitroindazole has been reported not to elevate blood pressure (McCall et al.,
      1991, Br. J. Pharmacol. 102, 234-238), fails to confirm the expected
      insensitivity of the constitutive endothelial nitric oxide synthase to inhibition
      by 7-nitroindazole.

PMID- 7526800
TI  - Tyrosine-phosphorylated calmodulin has reduced biological activity.
AB  - Calmodulin is phosphorylated by the purified insulin receptor on tyrosine
      residues with a maximum stoichiometry of 1 mol phosphate/mol of calmodulin.
      Isolated tryptic phosphopeptides were sequenced by manual Edman degradation and
      demonstrated that calmodulin is equally phosphorylated on tyrosine 99 and
      tyrosine 138. Phosphorylated calmodulin has a decreased affinity (K0.5 = 4.2 nM)
      for the 63-kDa isozyme of cyclic nucleotide phosphodiesterase compared to
      nonphosphorylated calmodulin (K0.5 = 2.1 nM). The K0.5 for Ca2+ is marginally
      increased from 2.8 to 3.2 microM in the presence of phosphotyrosyl calmodulin.
      The effect of the calmodulin antagonist, mastoparan, was investigated to
      determine whether mastoparan would differentially inhibit calmodulin- or
      phosphocalmodulin-dependent enzyme activity. The IC50 of mastoparan is fourfold
      lower for phosphotyrosyl calmodulin compared to nonphosphorylated calmodulin.
      Phosphorylation of calmodulin may provide a mechanism for the differential
      regulation of calmodulin-dependent enzymes. These observations further support a
      potentially important regulatory function of calmodulin phosphorylation in signal
      transduction.

PMID- 7526802
TI  - Effect of tacrolimus (FK506) in dystrophic epidermolysis bullosa: rationale and
      preliminary results.

PMID- 7526801
TI  - [Metastasis-related genes].
AB  - Genetic changes related to cancer metastasis are overviewed. hst-1/int-2 co
      amplification is closely related to the metastatic potential of esophageal
      carcinomas. Multiple autocrine and paracrine loops including EGF, TGF-alpha/EGF
      receptor system and HGF/c-met system are related to the biological malignancy of
      gastric carcinoma in general. On the other hand, K-sam and c-erbB2 amplification
      are frequently found in the metastatic foci of poorly and well-differentiated
      type gastric carcinoma. Various splice variants of cell adhesion molecule CD44
      are the potent marker of human carcinomas themselves as well as metastases.
      Reduction in the expression of nm23 is a relatively common event in the
      metastasis of various human cancers, including stomach and colorectal carcinomas.

PMID- 7526803
TI  - Intellectual development at 10 years in early treated congenital hypothyroidism.
AB  - Fifty nine children born between 1978 and 1981 with congenital hypothyroidism
      detected by neonatal screening were assessed at 10 years using the Wechsler
      intelligence scale for children, together with 59 matched classroom controls.
      Thirty one children with severe hypothyroidism who had pretreatment plasma
      thyroxine concentrations of 40 nmol/l or less had a mean (SD) full scale IQ score
      of 104.7 (15.1), compared with a mean (SD) score of 114.6 (16.3) for the 28 less
      severely affected children who had pretreatment thyroxine levels greater than 40
      nmol/l, and mean (SD) scores of 114.5 (12.8) and 114.8 (13.8) respectively for
      the 31 and 28 control children. In the hypothyroid children the IQ scores at 10
      years were closely related to the IQ scores at 5 years and at 3 years. It is
      concluded that the deficit in IQ score found at 3 and 5 years in children with
      severe hypothyroidism is still evident at the age of 10 years.

PMID- 7526804
TI  - Increased expression of adhesion receptors in both lesional and non-lesional
      psoriatic skin.
AB  - Adhesion receptors and their ligands play a vital role in the immune system. We
      studied the expression of different adhesion receptors, using single- and double
      staining immunohistochemical techniques, in both lesional and non-lesional skin
      specimens from seven psoriasis patients and in skin biopsy specimens from eight
      normal healthy controls. Our results showed an overall increased expression of
      several adhesion receptors in both lesional and non-lesional psoriatic skin. We
      consistently found an increased expression in particular of ICAM-1 and E-selectin
      on endothelial cells, and ICAM-1 on T cells and Langerhans cells. In contrast, a
      weak expression of VCAM-1 was found on endothelial cells and mononuclear cells in
      lesional psoriatic skin specimens alone. Interestingly, LFA-1 was also expressed
      on Langerhans cells, with a greater frequency in skin from lesional than from non
      lesional sites, but was never expressed in skin from normal healthy individuals.
      Furthermore, significantly increased numbers of Langerhans cells and T cells with
      a positive reactivity for MAb HECA-452 were found in both lesional and non
      lesional psoriatic skin. We hypothesize that the enhanced expression of adhesion
      receptors on migrating immunocompetent cells and endothelial cells of psoriatic
      skin in general facilitates the increased influx of activated T lymphocytes and
      other immunocomponent cells into the skin, and thus underscores the generalized
      character of the disease.

PMID- 7526805
TI  - Topical FK506: suppression of allergic and irritant contact dermatitis in the
      guinea pig.
AB  - Topical FK506 has recently been shown to have an anti-inflammatory effect in vivo
      in humans. In this study its effects in contact dermatitis were studied in the
      guinea pig model. Topical FK506 suppressed both irritant and allergic patch-test
      reactions. The most prominent suppressive effect was seen when skin sites were
      pretreated with FK506. Topical FK506 did not impair the induction of contact
      allergy as assessed by challenges, although it suppressed local lymph node cell
      accumulation during contact allergy induction. Topical FK506 may hold promise as
      a treatment for skin disorders that respond to oral FK506 or cyclosporin A.

PMID- 7526806
TI  - Substance P and calcitonin gene-related peptide modulate leukocyte infiltration
      to mouse skin during allergic contact dermatitis.
AB  - The effects of the neuropeptides substance P (SP) and calcitonin gene-related
      peptide (CGRP) on leukocyte infiltration during allergic contact dermatitis (ACD)
      in mice were studied. Concomitant topical application of SP or CGRP with the
      allergen oxazolone resulted in enhanced leukocyte recruitment at the sites of
      challenge. Immunohistochemical studies revealed that the numbers of T-helper
      (L3T4+) and cytotoxic (Lyt-2) lymphocytes and infiltrating macrophages (BM8+)
      were increased. In addition, ICAM-1 and MHC class II molecule expression by these
      cells was enhanced after neuropeptide application. Analysis by confocal laser
      scanning microscopy revealed an increase in the immunoreactivity for SP and CGRP
      in nerve fibres during the course of ACD. Flow cytometry studies showed that SP
      and CGRP did not upregulate expression of the adhesion molecules ICAM-1 and VCAM
      1 by murine endothelial cell lines in vitro. This suggests that increased
      infiltration of leukocytes during ACD is not a consequence of direct neuropeptide
      promoted upregulation of endothelial adhesion molecules in vivo. In conclusion,
      our observations provide evidence for a modulatory role of neuropeptides in the
      pathogenesis of ACD.

PMID- 7526807
TI  - Expectant management of suspected ectopic pregnancies even with rising beta
      subunit human chorionic gonadotropin levels. A clinical prospective study.
AB  - A prospective study was undertaken to evaluate possibility of expectant
      management of ectopic pregnancy in a selected group of patients with few
      symptoms, no gestational sac on sonography, and rising but low beta hCG levels.
      Using the above mentioned criteria, 26 patients were enrolled during prospective
      study period of 24 month. Five patients (19.2%) had a ruptured tubal pregnancy
      during the period of observation. Ten patients (38.5%) underwent laparoscopy with
      subsequent surgery for tubal pregnancy. The indication for laparoscopy in all 10
      cases was abdominal pain. In all these 10 patients the pregnancy was unruptured.
      The remaining 11 patients (42.3%) escaped surgical intervention. Three had
      intrauterine pregnancies. In the remaining 8 patients the diagnosis remained
      presumed ectopic. The mean interval from admission of beta hCG level of < 5
      mIU/ml in these 8 patients was 19.2 +/- 8.4 days. They were inpatients until the
      beta hCG level begun to decline. Thereafter, the patients were observed as
      outpatients. We conclude that in carefully selected cases of suspected ectopic
      pregnancies with rising but low beta hCG levels, expectant management is
      appropriate as long as the patient remains relatively asymptomatic.

PMID- 7526810
TI  - Combined aprotinin and erythropoietin use for blood conservation: results with
      Jehovah's Witnesses.
AB  - Despite recent advances in blood conservation techniques, major risks persist for
      excessive bleeding and blood transfusion after open heart operations. We reviewed
      the records of 100 consecutive patients undergoing first-time coronary artery
      bypass grafting at our institution to define these risks and develop a
      multimodality blood conservation program based on the results. This program was
      subsequently applied on a prospective basis to a select group of patients who
      refuse blood transfusion on religious grounds (Jehovah's Witnesses [JW]) (n =
      15). Encouraging initial results with coronary artery bypass grafting in this
      group (n = 8) led to the application of the program to more complex operations (n
      = 7), including repeat bypass grafting with use of the internal mammary artery,
      repeat mitral valve replacement, aortic and mitral valve replacement with
      coronary artery bypass grafting, mitral valve replacement with bypass grafting,
      chronic type 1 dissection repair, aortic valve replacement, and atrial septal
      defect repair in 1 patient each. The blood conservation program employed in these
      patients included the use of (1) aprotinin (full Hammersmith regimen), (2) high
      dose erythropoietin, (3) "maximal"-volume intraoperative autologous blood
      donation, (4) low-prime cardiopulmonary bypass, (5) exclusive use of
      intraoperative cell salvage, and (6) continuous reinfusion of shed mediastinal
      blood. There were no deaths in the JW group. Thromboembolic complications
      consisted of a transient posterior circulation stroke in only 1 patient
      (dissection repair). No blood or blood products were transfused compared with the
      transfusion of 5.1 +/- 7.8 units (mean +/- standard deviation) in the 100 primary
      coronary bypass patients in whom the blood conservation program was not
      employed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526811
TI  - Metaanalysis of prophylactic drug treatment in the prevention of postoperative
      bleeding.
AB  - Prophylactic drug treatment is one of several strategies to reduce postoperative
      blood loss and potentially limit homologous blood use in open heart surgery. A
      computerized MEDLINE search supplemented with manual bibliography reviews was
      performed for randomized clinical trials published in peer-reviewed English
      language journals from January 1980 to June 1993. A metaanalysis was conducted of
      trials evaluating desmopressin (group DD, n = 13), epsilon-aminocaproic acid or
      tranexamic acid (group EA, n = 4), and aprotinin (group AP, n = 16). Eligible
      studies used placebo controls and administered the drug in a prophylactic manner.
      The primary study end point was postoperative chest tube loss (mL, mean +/-
      standard deviation). There was a significant reduction in postoperative chest
      tube loss detected for each of the active treatments versus the placebo (DD
      versus controls: percent reduction 0.11, p = 0.0021; EA versus controls: percent
      reduction 0.30, p < 0.0001; and AP versus controls: percent reduction 0.36, p <
      0.0001). Therapy with EA or AP was associated with a greater reduction in chest
      tube loss than DD (EA versus DD, p = 0.0033, and AP versus DD, p < 0.0001).
      Secondary study end points were transfusion requirements, chest reexploration,
      and perioperative mortality. The volume of postoperative red cell transfusion
      (mean +/- standard deviation) was reduced with EA (p < 0.0001) or AP treatment (p
      < 0.0001) compared with a placebo or DD, whereas the proportion of patients given
      transfusions was limited only in the AP-treated patients (odds ratio 0.23; 95%
      confidence interval, 0.16 to 0.33; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526809
TI  - Basic fibroblast growth factor identified in chronically stimulated
      cardiomyoplasties.
AB  - In the presence of myocardial ischemia, chronic electrical stimulation of a
      latissimus dorsi (LD) cardiomyoplasty enhances extramyocardial collateral blood
      flow. We postulated that basic fibroblast growth factor (bFGF) may mediate
      extramyocardial collateral formation. To test this hypothesis, LDs from goats
      with cardiomyoplasties were probed for the presence of bFGF by Western blot
      analysis and immunohistochemistry. Three groups were studied: static LD
      cardiomyoplasty (group 1); LD cardiomyoplasty stimulated at a 2-Hz frequency for
      6 weeks (group 2); and LD cardiomyoplasty electrically stimulated and given human
      recombinant bFGF (group 3). There was no evidence of bFGF in the left LDs of
      group 1 by Western blot. Basic fibroblast growth factor-like immunoreactive
      evidence was found in the left LDs of group 2 goats by both Western blot and
      immunohistochemistry. In the right LDs of group 2, bFGF-like material was found
      by immunohistochemistry but not by Western blot, which suggests that the tissue
      concentrations were low (near the limits of detection). The left LDs of group 3
      were positive for bFGF by Western blot and immunohistochemistry. Group 3 right
      LDs were positive for bFGF by immunohistochemistry. Immunohistochemical findings
      in group 2 indicate that bFGF is present in goat skeletal muscle. Western blot
      data from groups 1 and 2 suggest that bFGF may be increased in chronically
      stimulated cardiomyoplasties. From findings in group 3, we conclude that
      exogenous bFGF does not downregulate, and may upregulate, endogenous production.
      These results support the possibility that skeletal muscle bFGF is an important
      factor in extramyocardial collateral formation.

PMID- 7526812
TI  - Dextran 40 at 2% versus 5% in low-potassium solutions: which is best?

PMID- 7526808
TI  - Interleukin 4 increases human synovial cell expression of VCAM-1 and T cell
      binding.
AB  - OBJECTIVE: The effects were studied of interleukin 4 (IL-4) on T cell-synovial
      cell adhesion and on the expression of adhesion molecules on the surface of
      synovial fibroblast-like cells. METHODS: The adhesion of T cells toward the
      synovial cells were measured by 51chromium-labelled adhesion assay. The
      expression of adhesion molecules on synovial cells were analysed by
      flowcytometry. RESULTS: Stimulation of synovial cells with IL-4 increased T cell
      synovial cells adhesion in a time- and dose-dependent manner. IL-4 considerably
      enhanced the expression of VCAM-1 on the surface of synovial cells, but not the
      expression of ICAM-1 and ELAM-1. The combination of IL-1 beta and IL-4 had no
      effect on the expression of ICAM-1 or VCAM-1 on the surface of synovial cells.
      The increased adhesion of T cells to IL-4 stimulated synovial cells was inhibited
      significantly by adding anti-VCAM-1 or anti-CD29 monoclonal antibody.
      Furthermore, anti-VLA-4 alpha or the combination of anti-VLA-4 alpha and anti
      VCAM-1 antibodies blocked completely T-cell binding to IL-4 stimulated synovial
      cells. CONCLUSIONS: These results suggest that the increased adhesion of T cells
      to IL-4-stimulated synovial cells is mediated by VLA-4/VCAM-1 pathway.

PMID- 7526815
TI  - Projections from the primary auditory cortex onto the dorsal cortex of the
      inferior colliculus in albino rats.
AB  - The topography of connections from the primary auditory cortex (Te1) onto the
      dorsal cortex (DC) of the inferior colliculus (IC) was studied using the
      anterograde neural tracers Phaseolus vulgaris (PHA-L) and Biotinylated dextran
      amine (BDA). Injections in different restricted portions of the ventral Te1
      showed labelled axonal sheets in the ipsilateral DC with extensions in the
      central nucleus and the external cortex. Also contralateral labelled axons were
      found with a patchy appearance. The pattern of labelled axonal laminae is
      arranged in an orderly fashion, so that a correlation exists between the
      injection field (antero-to caudoventral injections) and the pattern of labelled
      axonal sheets (from a ventromedial to a dorsolateral arrangement) in the IC.
      However, variations from this pattern were observed. Also only the injections
      made in rostral and middle parts of Te1 V are orderly arranged in the territory
      of the DC, while the Te1 V caudoventral projection partially overlaps those from
      antero and mid-central regions. A topographical arrangement in the fibre
      projection from the medial and dorsal zones of Te1 (Te1 D) exists in the neuropil
      of the IC. The bands from Te1 D overlapped with the bands from Te1 V but in
      different order. This indicates that the projection of the mid-dorsal zone of Te1
      is not topographically arranged in the DC like Te1 V. Based on the results we
      have obtained, there is strong evidence that the projection from Te1 V to the DC
      is topographically organized in a rostrocaudal sequence which gives definite
      terminal fields. However, each of these fields (medial, central and external)
      receives a principal bulk of primary auditory cortical fibres and a supplementary
      one. This implies that territories of the DC which contain neurons responsive to
      low frequencies receive a projection from Te1 fields with neurons which are
      responsive to high or to low frequencies.

PMID- 7526814
TI  - Role of endotoxin in L-arginine-induced relaxation of rat thoracic aorta mediated
      by muscle-derived nitric oxide.
AB  - The contribution of endotoxin to the L-arginine-induced relaxation of the
      endothelium-denuded rat thoracic aorta, which appears to be mediated by nitric
      oxide synthase in the vascular smooth muscle, was investigated. Special attention
      was paid to the time course of the phenomenon and its dependence on the
      concentration of endotoxin. In the absence of endotoxin, L-arginine induced
      scarcely any relaxation of the arteries. Treatment of the arteries with endotoxin
      initiated relaxation in response to 10 microM L-arginine with lag periods of 2-4
      hours. The degree of relaxation increased on repeated applications of L-arginine,
      to reach a consistent level after several hours. Increase in the concentration of
      endotoxin shortened the lag period, enhanced the degree of relaxation and lowered
      the threshold concentration of L-arginine required to relax the arteries. In
      endotoxin-primed arteries, L-arginine, at concentrations necessary to induce
      relaxation, stimulated the cyclic GMP production. Prophylactic application of
      actinomycin D or dexamethasone, which inhibits the induction of nitric oxide
      synthase, prevented the induction by endotoxin of the L-arginine-induced
      relaxation and cyclic GMP formation. Polymyxin B, which inhibits the action of
      endotoxin, also prevented the development of the endotoxin-sensitized relaxation
      and the cyclic GMP formation induced by L-arginine. When the Krebs solution was
      prepared using deionized water, the amount of endotoxin in the reservoir was
      above the level required to initiate the L-arginine-induced relaxation and cyclic
      GMP formation. These results suggest that endotoxin triggered the time-dependent
      development of the L-arginine-induced relaxation by expressing nitric oxide
      synthase in the vascular smooth muscle.

PMID- 7526813
TI  - [Biologically active substances formed by a number of strains of the actinomycin
      C producer--Streptomyces chrysomallus].
AB  - Biologically active substances produced by some strains of S. chrysomallus and
      their mutants with different levels of the differentiation were studied. Along
      with actinomycin C the strains produced macrotetrolides, bacteriocins and A
      factor-like substances. It was shown that the plasmid status of the strains was
      different. This suggested that the plasmid presence was a characteristic of the
      strains and the production of the studied substances was likely typical of S.
      chrysomallus.

PMID- 7526816
TI  - Galanin-like immunoreactivity in the cat brainstem.
AB  - The distribution of galanin-like immunoreactive fibers and cell bodies has been
      studied in the cat brainstem. Perikarya containing galanin were only found, at a
      low density, in the nucleus of the brachium of the inferior colliculus and in the
      pericentral nucleus of the inferior colliculus. The highest density of
      immunoreactive fibers was found in the laminar spinal trigeminal nucleus and in
      the parvocellular division of the alaminar spinal trigeminal nucleus. A moderate
      density of immunoreactive fibers was observed in the periaqueductal gray, locus
      coeruleus, marginal nucleus of the brachium conjunctivum and below the facial
      nucleus, whereas a low density of such fibers was found in the nucleus of the
      brachium of the inferior colliculus, pericentral nucleus of the inferior
      colliculus, nucleus incertus, medial division of the dorsal nucleus of the raphe,
      accessory dorsal tegmental nucleus, Kolliker-Fuse nucleus, lateral tegmental
      field, postpyramidal nucleus of the raphe, pericentral division of the dorsal
      tegmental nucleus, infratrigeminal nucleus, medial nucleus of the solitary tract,
      spinal trigeminal tract, dorsal motor nucleus of the vagus, and in the lateral
      reticular nucleus. According to the distribution of galanin-like immunoreactive
      structures in the cat brainstem, our data suggest that the peptide could be
      involved in respiratory, cardiovascular, nociceptive and auditory mechanisms.

PMID- 7526818
TI  - Advanced prostate cancer with normal serum prostate-specific antigen values.
AB  - Prostate-specific antigen is a specific and sensitive marker of prostate cancer,
      and most patients with advanced prostate cancer have elevated serum prostate
      specific antigen values. Over a period of 45 months, 976 cases of advanced
      prostate cancer (stages C and D) were investigated to determine the serum
      prostate-specific antigen level at presentation. Eight cases of advanced prostate
      cancer are documented in which the serum prostate-specific antigen values were
      within normal limits. Six of the eight cases showed the features of invasive
      moderately differentiated acinar carcinoma; one case of small-cell carcinoma and
      one of cribriform carcinoma were noted. Direct immunohistochemical assessment of
      tumor tissue was performed, and the correlation between monoclonal and polyclonal
      antibody staining was assessed. In seven of the eight cases, monoclonal
      antibodies showed no convincing staining, while all but one (small cell) were
      positive for polyclonal stains.

PMID- 7526817
TI  - The measurement of fibrinogen in population-based research. Studies on
      instrumentation and methodology.
AB  - Plasma fibrinogen concentration is a risk factor for cardiovascular disease and
      has become a common component of epidemiologic studies. Also, fibrinogen analysis
      has become an important component of clinical trials of thrombolytic therapy and
      anticoagulation. We studied fibrinogen values from plasma containing three
      different anticoagulants and compared two different instruments. Clot-rate assays
      were performed on plasma containing sodium citrate (the recommended specimen) as
      well as ethylenediamine-tetraacetic acid (EDTA) and EDTA plus D-Phe-Pro-Arg
      chloromethyl ketone (PPACK) and aprotinin (special anticoagulant), specimens
      often obtained in multicenter studies. We compared a fibrometer (the BBL) with an
      analyzer (the Diagnostica Stago ST4), which offers improved throughput, ease of
      use, and precision. The correlation of citrate and EDTA fibrinogen values
      (fibrometer) was r = .9718; for citrate and special anticoagulant plasma, r =
      .9717. Correlations of fibrinogen values from the fibrometer and the analyzer
      were r = .9558 and r = .9857 for citrate samples and special anticoagulant
      samples, respectively. We conclude that (1) fibrinogen may be measured by clot
      rate assay in EDTA-containing samples and that values may be compared with values
      obtained from citrate plasma with a correction; (2) samples containing PPACK may
      be used with only slight modification of the method; and (3) values obtained on
      the analyzer are directly comparable with those obtained on the fibrometer,
      facilitating large studies.

PMID- 7526819
TI  - A rapid technique of acetylcholinesterase staining.
AB  - When tissue samples are evaluated for the presence of Hirschsprung's disease,
      results of acetylcholinesterase staining are usually more informative than
      findings from the routine hematoxylin-eosin method. The standard technique for
      staining acetylcholinesterase takes 2 hours to perform and is based on the enzyme
      histochemical method of Karnovsky and Roots, with a subsequent visualization step
      as described by Hanker and colleagues. We modified the technique by the
      introduction of supplemental oxidation, which accelerated the staining time to
      less than 10 minutes. When evaluated in 10 patients with Hirschsprung's disease
      and in seven control patients with normal colons, the rapid technique gave
      identical staining of nerves and ganglion cells to that of the standard method.
      Increased visualization of endogenous peroxidase-containing histiocytes occurred,
      but it was not a diagnostic problem. The technique is sufficiently rapid to be
      used in conjunction with routine frozen sections to assist in the diagnosis and
      in selecting the optimal level of resection at the time of definitive surgery.

PMID- 7526820
TI  - Serum cytokine levels in patients with neutropenia.
AB  - Serum samples from 76 patients with neutropenia and 34 control subjects were
      analyzed for levels of granulocyte colony-stimulating factor, granulocyte
      macrophage colony-stimulating factor, interleukin 1 alpha, and tumor necrosis
      factor beta. Clinical correlates and duration of neutropenia were determined
      insofar as possible. Systemic acute inflammatory disease was present in only two
      patients. In most cases, the neutropenia was considered idiopathic or medication
      related. Significantly elevated serum granulocyte colony-stimulating factor
      levels were found in the patient group, regardless of the apparent cause of the
      neutropenia. Increased levels of granulocyte-macrophage colony-stimulating
      factor, interleukin 1, and tumor necrosis factor were seen in only one patient
      with sepsis.

PMID- 7526821
TI  - Acute-phase hepatocytes regulate liver sinusoidal cell mediator production.
AB  - BACKGROUND: Overproduction of liver sinusoidal cell (LCS) mediators in response
      to endotoxemia or gram-negative infection that follows tissue injury may
      contribute to hepatic dysfunction. OBJECTIVE: To better define the role of
      hepatocyte-derived acute-phase reactants in the regulation of sinusoidal cell
      mediator production following sequential insults, we tested the hypothesis that
      interleukin-6 (IL-6) prestimulation alters hepatocyte regulation of
      lipopolysaccharide (LPS)-stimulated sinusoidal cell tumor necrosis factor (TNF),
      IL-6, and nitric oxide production. METHODS: Hepatocytes and LSCs were isolated
      from Wistar rats, and in vitro responses were compared between LSCs alone and
      hepatocyte-LSC cocultures. Cocultures and LSCs alone were sequentially stimulated
      with IL-6 (5000 U/mL) then LPS (dose-response), and culture supernatants were
      analyzed for TNF (L929 cytolysis), IL-6 (7TD1 proliferation), and nitric oxide
      (Griess reaction). Induction of acute-phase protein synthesis by the stimulation
      of hepatocytes with IL-6 and dexamethasone (0.1 mumol/L) was assayed by
      methionine radiolabeling and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis). Coculture levels of messenger RNA for TNF-alpha and IL-6 were
      examined by RNA extraction and reverse transcriptase polymerase chain reaction
      with specific primers. RESULTS: Interleukin-6 and dexamethasone signal hepatocyte
      acute-phase protein synthesis. Prestimulation of cocultures, but not of LSCs
      alone, with IL-6 inhibits LPS-stimulated IL-6 and nitric oxide production
      significantly. Bioactivity of TNF is reduced to a lesser extent. Polymerase chain
      reaction analysis demonstrated similar levels of TNF and IL-6 message following
      sequential stimulation. CONCLUSIONS: Interleukin-6-stimulated acute-phase
      hepatocytes limit LPS-stimulated coculture cytokine bioactivity and nitric oxide
      production. This hepatocyte response may provide a local counterregulatory
      mechanism to limit LSC-mediated injury.

PMID- 7526822
TI  - Production and characterization of monoclonal antibodies to plum pox virus and
      their use in differentiation of Mediterranean isolates.
AB  - Monoclonal antibodies (MAbs) specific to plum pox virus (PPV) were prepared by
      fusing myeloma cell lines to spleen cells of mice immunized with purified virus,
      including virus prepared with protease inhibitors to preserve the integrity of
      the coat protein (CP). The characterized MAbs could be used in ELISA to
      differentiate several Mediterranean PPV isolates differing in their geographical
      origin and CP size. At least seven antigenic sites could be established based on
      the recognition pattern and competition binding analysis, and the epitopes could
      be classified in three groups by Western blot analysis of intact and trypsin
      digested virus particles. By means of electron microscopy the epitopes could be
      seen to be located on the surface of the virus particles.

PMID- 7526825
TI  - Monoclonal antibodies reactive with specific amino acid sequences of the 126 K
      protein of tobacco mosaic virus.
AB  - The 126 K protein of tobacco mosaic virus (TMV) is an NTP binding protein that
      has guanylyl transferase activity and is predicted to be an ATPase/helicase. In
      this paper we report the generation of monoclonal antibodies (Mabs) that react
      with specific amino acid sequences of the 126K protein. The Mabs were generated
      after immunizing mice with a partially purified preparation of the 126 K protein
      (native) obtained by centrifugal fractionation of the infected tissue extracts.
      The Mabs were assayed for specific reactivity by western blotting and by their
      reactivity with non-overlapping decapeptides corresponding to the entire amino
      acid sequence of the 126 K protein of TMV. A total of 11 Mabs reactive with
      specific peptides and three other Mabs that did not react with any peptide but
      reacted with the 126 K protein were identified.

PMID- 7526823
TI  - Differences in antigenicity of E2 in Semliki Forest virus particles and in
      infected cells.
AB  - Using six monoclonal antibodies to epitopes a-f on the glycoprotein E2 of Semliki
      Forest virus (SFV) we found antigenic differences between E2 in infected cells
      and in virus particles, respectively, if glycosylation was impaired by 2-deoxy-D
      glucose or inhibited by N-methyl-1-deoxynojirimycin. Furthermore we concluded
      that a conformational change of E2 takes place on virus budding.

PMID- 7526827
TI  - The nature of multimeric forms of cymbidium ringspot tombusvirus satellite RNA.
AB  - The multimeric forms of cymbidium ringspot tombusvirus (CyRSV) satellite (sat)
      RNA were analysed. Attempts to amplify the putative junction region of oligomers
      using the polymerase chain reaction (PCR) failed, indicating the absence of such
      structures. SatRNA-related species having the size double than the unit length
      were shown to be double-stranded monomers and not single-stranded dimers.
      Similarly, satRNA species of a size four times the unit length were shown to be
      constituted by aggregates of double-stranded monomers. The absence of single
      stranded CyRSV satRNA oligomers indicates that the formation of multimers is not
      a step in the replication of this RNA molecule.

PMID- 7526828
TI  - [Release of chemical mediators in the conjunctival lavage fluids after eye
      provocation with allergen or compound 48/80].
AB  - Allergen extract was used to perform conjunctival provocation test on patients
      with Japanese cedar pollen conjunctivitis during the off-season, and histamine,
      tryptase and immunoreactive-leukotriene C4 (i-LTC4), which mainly consisted of
      LTE4, were measured in the lavage fluids. The results obtained in this study were
      as following. 1) After instillation of the allergen extract (1:20, w/v, 0.01 ml),
      histamine reached a maximal level of 4.63 +/- 1.67 ng/ml (mean +/- SE, n = 11) at
      5 min. Tryptase appeared more slowly and the peak levels were reached at 5 min
      (116.6 +/- 49.6 ng/ml) or 10 min (119.4 +/- 63.8 ng/ml). In another set of the
      experiments, histamine peaked at 5 min (3.84 +/- 1.08 ng/ml, n = 7), and i-LTC4
      reached peaks at 5 min (320 +/- 44.4 pg/ml) or 10 min (367 +/- 64.8 pg/ml). The
      amounts of these mediators decreased to base-line levels by 30 min. 2) The
      amounts of histamine retrieved from the lavage fluid were significantly
      correlated with those of tryptase (r = 0.819, p < 0.01, n = 11) and the weight
      ratio of tryptase to histamine was 41.2 +/- 10.0. These observations suggest that
      histamine was released from mast cells. 3) A significant correlation between the
      levels of histamine and i-LTC4 recovered from the lavage fluids was also observed
      (r = 0.736, p < 0.05, n = 7). 4) Compound 48/80 was instilled in the right eye
      (7.5 mg/ml, 0.01 ml) and the left eye was given allergen solution.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7526826
TI  - Inhibition of myelin formation by HIV-1 gp120 in rat cerebral cortex culture.
AB  - To study the role of HIV-1 gp120 in loss of myelin in HIV encephalopathy, the
      binding of gp120 to various types of neural cells and its effects on myelination
      were examined in rat primary brain culture. Double-staining of cultured cells
      with gp120 and specific antibodies for different neural cell types showed that
      gp120 bound to most of the galactocerebroside (GalC)-positive oligodendrocytes, a
      small population of type-2-like astrocytes and a few small neurons. Gp120 did not
      bind to type-1-like astrocytes, most neurons, or to macrophage/microglia. To
      assay myelination, cells were bathed in a myelination medium containing chick
      embryo extract and high glucose, with or without gp120. Seven days after the
      application, myelination in the culture was observed morphologically and by
      staining with anti-myelin basic protein (MBP) antibody, and was found to be
      significantly inhibited by the addition of gp120 (50-100 nM). The processes of
      oligodendrocytes were reduced in length and arborization relative to the control,
      but MBP production by oligodendrocytes was unaffected. These results show that
      gp120 can cause a functional disorder of oligodendrocytes and thus could underlie
      the diffuse loss of myelin sheaths of HIV encephalopathy.

PMID- 7526829
TI  - A low-molecular-size LM2 allergen in mite, Dermatophagoides farinae, extracts
      containing feces which elicits conjunctival reactions in patients with bronchial
      asthma.
AB  - A low-molecular-size antigen, LM2, which possesses a significant activity to
      elicit histamine release, was isolated from an ultrafilterable (Mr-cutoff < 10k)
      fraction of a mite extract containing feces by consecutive chromatography on
      Ultrogel AcA 54 and Sephadex G-25. The isolated antigen was still heterogeneous
      glycoproteins, giving a smeary band around pI 3-5 on an Ampholine PAG plate, with
      molecular weights of 6-8k and 4k on SDS-PAGE and Sephadex G-50 gel filtration,
      respectively. Chemical treatments of the antigen suggested that the epitope
      responsible for the elicitation of histamine release resided in the protein
      moiety. The antigen had activities to provoke conjunctival congestion and
      histamine release in mite-allergic patients, but not immunogenicity by itself.
      The antigen competitively inhibited the reactions of HM1, HM2, and HM3 fractions
      to corresponding antisera, but did not cross-react with anti-Der f I or anti-Der
      f II sera.

PMID- 7526831
TI  - [The morphological characteristics of the fibromyalgia syndrome].
AB  - A histological and ultrastructural study of dense foci characteristics for soft
      tissues in fibromyalgia syndrome revealed that they consist of rough fibrillar
      connective tissue frequently hyalinized. Vascularization occurred at the
      periphery of these foci only where thin nervous fibrils and sometimes small
      paraganglia were seen. Severe degenerative changes of the collagen fibers, marked
      decrease and degeneration of fibroblasts were found electron microscopically.
      Signs of inflammation were absent.

PMID- 7526830
TI  - Comparison between isolated rat and guinea pig aortae in response to drugs.
AB  - Comparison between isolated rat and guinea pig aortae in response to drugs was
      made. The data indicated that the norepinephrine and KCl concentration effect
      curves determined in rat aortae were on the left of those determined in guinea
      pig aortae. When aortae were preconstricted with 60 mM KCl, the relaxation
      induced by nitroprusside or 3-isobutyl-1-methyl-xanthine was more potent than
      those in guinea pig aortae. Although bethanechol and isoproterenol were effective
      to relax rat aortae preconstricted with 1 x 10(-5) M norepinephrine, yet guinea
      pig aortae preconstricted with norepinephrine were not responsive to bethanechol
      and isoproterenol in similar concentrations tested. The above results suggested a
      difference between rat and guinea pig aortae in response to drugs.

PMID- 7526832
TI  - [Immunomorphological study of human tumors using the monoclonal antibody RMZh-1].
AB  - Monoclonal antibodies (MAB) were obtained against the antigens isolated from the
      fraction of external plasmatic membranes of human breast cancer (RMZh-I). 170
      epithelial and non-epithelial primary and metastatic human tumours of various
      localization were studied by an immunoperoxidase method using the above
      antibodies. Positive reactivity with RMZh-I was observed in the epithelial tumors
      of mammary gland, uterus, ovaries, thyroid, lung, gastrointestinal tract, kidney.
      Mab did not react with hematopoietic and sarcomatous tumours. The parameters of
      the immunoperoxidase reaction were identical at both histologic and cytologic
      levels. MAB RMZh-I may be used as an epithelial marker for differential diagnosis
      of carcinoma metastases and lymphoproliferative disease.

PMID- 7526833
TI  - Nerve fibres and cells immunoreactive to neurochemical markers in developing rat
      molars and supporting tissues.
AB  - The distribution of nerve fibres immunoreactive to calcitonin gene-related
      peptide (CGRP), substance P (SP) and neuropeptide Y (NPY) was compared to the
      general neurochemical markers for nerves and neuroendocrine cells protein gene
      product 9.5 (PGP 9.5) and neurone-specific enolase (NSE), by use of the avidin
      biotin peroxidase complex method in developing dental structures in rats aged 13
      to 27 days. A substantially greater part of the nerve fibres was immunoreactive
      to CGRP and SP than to NPY. In the bell stage, nerve fibres immunoreactive to PGP
      9.5, CGRP and SP were found in the dental follicle but not in the dental papilla
      and stellate reticulum. In the advanced bell stage, after initiation of dentine
      and enamel formation, PGP 9.5, CGRP- and SP-immunoreactive fibres were found in
      the dental papilla, while the first NPY-immunoreactive fibres were observed in
      the papilla when root formation started. Concomitant with the beginning of root
      development, a subodontoblastic nerve plexus was gradually formed and PGP 9.5-,
      CGRP- and SP-immunoreactive fibres were found within the dentinal tubules. From
      the start of root formation, CGRP-, SP- and NPY-immunoreactive nerves were shown
      in the developing periodontal ligament, although a mature distribution pattern
      was not observed until root formation was nearly completed. Ameloblasts,
      odontoblasts and cell-like structures in the outer enamel epithelium and within
      the dental lamina were PGP 9.5-immunoreactive at the bell stage. As the tooth
      matured, the immunolabelling gradually decreased, but was still present in some
      odontoblasts after tooth eruption. NSE-immunoreactive, cell-like structures were
      found in the periphery of the dental follicle, and persisted close to alveolar
      bone in the periodontal ligament when the tooth reached occlusion. Hence, it may
      be concluded that sensory nerves containing SP and CGRP are present in the pulp
      in advance of sympathetic nerves immunoreactive to NPY.

PMID- 7526834
TI  - Specific immune response to the 40-kDa outer-membrane protein of Porphyromonas
      gingivalis in mice.
AB  - Whether B-cell activation to Porphyromonas gingivalis in periodontal diseases is
      the consequence of a specific immune response or is due to non-specific
      polyclonal activation is still not clear. Here the immune response of mice to a
      purified 40-kDa recombinant protein antigen, a major outer-membrane protein
      specific to P. gingivalis, was investigated. Patients' sera strongly reacted to
      this recombinant antigen. Purified splenic T and B cells from mice immunized with
      40-kDa antigen or from normal mice were reconstituted in vitro and cultured in
      the presence or absence of the P. gingivalis 40-kDa protein antigen and antigen
      presenting cells (APCs). In vitro antibody production to this particular antigen
      was analysed with respect to the requirement of helper T cells and APCs by enzyme
      linked immunosorbent assay. The results clearly showed that an effective
      secondary response required the presence of B cells, T cells and APCs. In the
      absence of CD4+ helper T cells, an antibody response to the 40-kDa protein was
      not observed. In addition, the requirement of H-2 restricted, Ia-positive APCs
      was evident for an adequate response to the 40-kDa protein of P. gingivalis. Thus
      the antibody response to the 40-kDa protein of P. gingivalis was generated in an
      immunologically antigen-specific manner and was not simply the result of
      polyclonal B-cell activation. This in vitro system could be used in the detection
      of antigen-specific memory B or T cells in patients with periodontal diseases.

PMID- 7526824
TI  - Human immunodeficiency virus type 1 (HIV-1) and human hematopoietic progenitor
      cells.
AB  - Besides a progressive depletion of CD4+ T-lymphocytes, other peripheral blood
      cytopenias, (granulocytopenia, anemia and thrombocytopenia) are frequently
      observed in HIV-1 seropositive individuals, especially in patients with overt
      AIDS. Various experimental evidences suggest that HIV-1 could play a direct role
      in the pathogenesis of HIV-1 related peripheral blood cytopenias, affecting the
      survival/proliferation capacity of hematopoietic progenitors. CD34+ human
      hematopoietic progenitors, however, are substantially not susceptible to HIV-1
      infection either in vitro and in vivo and their defects seem rather related to an
      alteration of bone marrow and peripheral blood microenvironments due to the
      presence of soluble HIV-1 specific products.

PMID- 7526835
TI  - Current thinking in the management of leukaemia.
AB  - The leukaemias are a diverse group of bone marrow malignancies. In general, the
      acute leukaemias are potentially curable with standard combination chemotherapy
      but the chronic leukaemias, despite a more prolonged, indolent course, are
      incurable. Newer antimetabolite agents offer the promise of improved survival in
      the chronic leukaemias of lymphocytic origin. Although it may not be indicated
      for all types and is generally suitable only for younger patients, bone marrow
      transplantation provides improved prospects for cure for most types of leukaemia
      and the only chance of cure for some.

PMID- 7526837
TI  - Intermittent dosing of granulocyte colony stimulating factor (G-CSF) to
      facilitate palliative radiotherapy.

PMID- 7526836
TI  - Electron microscopic immunohistochemical study of intra-epithelial nerve fibers
      in the canine larynx.
AB  - Substance P (SP)-, calcitonin gene-related polypeptide (CGRP)-, and vasoactive
      intestinal polypeptide (VIP)-immunoreactive (IR) nerve fibers were observed in
      the epithelium of the canine subglottic region. To investigate the morphological
      differences among SP-, CGRP-, and VIP-IR nerve fibers in the epithelium, this
      study was performed by using immunohistochemical staining and electron
      microscopy, after which the origins of the nerve fibers were examined by
      denervation of the bilateral superior and inferior laryngeal nerves. SP- and CGRP
      IR nerve fibers entered the epithelium through the basement membrane, ascended
      among the basal and ciliated cells, and reached under the epithelial junctional
      complex to terminate with varicosities. Furthermore, subsurface cistern-like
      structures or bouton en passant type synapse-like structures were observed among
      some varicosities of these nerve fibers and ciliated cells in the epithelial
      apical portion. On the other hand, VIP-IR nerve fibers entered through the
      basement membrane, and terminated with varicosities at the height of the middle
      portion of the subglottic epithelium. The varicosities of the VIP-IR nerve fibers
      were larger, and these varicosities had a greater number of synaptic vesicles
      than the SP- or CGRP-IR nerve fibers. After section of the bilateral superior and
      inferior laryngeal nerves, the SP- and CGRP-IR nerve fibers disappeared, while
      the VIP-IR nerve fibers were not affected. The density and distribution pattern
      of VIP-IR nerve fibers clearly differed from the SP- and CGRP-IR nerve fibers of
      sensory origin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526838
TI  - Mitogen-induced lymphocyte proliferation and interferon production following
      coccidia infection.
AB  - Concanavalin A-induced lymphocyte proliferation and interferon production were
      measured following infection with Eimeria acervulina in lines of chickens
      congenic at the major histocompatibility complex and in two unrelated lines.
      Similar proliferation responses were seen for splenic and peripheral blood
      lymphocytes following primary but not secondary infection. Greater differences in
      lymphocyte proliferation were found between the congenic lines and unrelated
      lines than among the congenic lines. The congenic lines had very low responses to
      Con A, in terms of both lymphocyte proliferation and interferon production. At
      some times after infection, background proliferation in all lines was higher for
      infected than uninfected chickens, which was probably an indication of activated
      lymphocytes in the circulation. Mitogen-induced lymphocyte proliferation and
      interferon production, although clearly affected by coccidial infection, were not
      reflective of severity of infection.

PMID- 7526839
TI  - Isotype, specificity, and kinetics of systemic and mucosal antibodies to
      Campylobacter jejuni antigens, including flagellin, during experimental oral
      infections of chickens.
AB  - The immune response of chickens to Campylobacter jejuni infection was studied as
      a step in the search for vaccine candidates. One-day-old chicks orally challenged
      with C. jejuni strain 81116 showed significant increases in specific IgG, IgA,
      and IgM circulating antibodies, as detected by enzyme-linked immunosorbent assay
      (ELISA). These levels peaked at 9, 5, and 7 weeks postinfection, respectively.
      Maternal IgG antibodies were also detected over the first 2 weeks. Specific
      mucosal IgG and IgA antibody levels also increased significantly. All of the
      birds demonstrated a major response to the 62-kDa flagellin protein by Western
      blotting techniques. The immunodominance of flagellin was confirmed by ELISA
      using an antigen preparation from an aflagellate mutant. When overlapping
      recombinant polypeptide fragments of flagellin were used, epitopes detected by
      chicken antibodies were observed in region IV, between residues 95-340 of the
      protein. Thus flagellin may be suitable candidate for a vaccine, although its
      role in protection must first be established.

PMID- 7526841
TI  - Thrombin-receptor agonist peptides, in contrast to thrombin itself, are not full
      agonists for activation and signal transduction in human platelets in the absence
      of platelet-derived secondary mediators.
AB  - Synthetic thrombin receptor peptides (TRPs), comprising the first 6-14 amino
      acids of the new N-terminus tethered ligand of the thrombin receptor that is
      generated by thrombin's proteolytic activity, were reported to activate platelets
      equally with thrombin itself and are considered to be full agonists [Vu et al.
      (1991) Cell 64, 1057-1068]. Using aspirin plus ADP-scavengers or the ADP-receptor
      antagonist adenosine 5'-[alpha-thio]triphosphate to prevent the secondary effects
      of the potent agonists that are normally released from stimulated platelets (i.e.
      ADP and thromboxane A2), we assessed the direct actions of thrombin and TRPs
      (i.e. TRP42-47 and TRP42-55). Compared with thrombin, under these conditions,
      TRPs: (1) failed to aggregate platelets completely; (2) produced less activation
      of glycoprotein (GP)IIb-IIIa; (3) did not cause association of GPIIb and pp60c
      src with the cytoskeleton; and (4) caused less alpha-granule secretion,
      phosphorylation of cytoplasmic phospholipase A2, arachidonic acid release and
      phosphatidyl inositol (PtdOH) production. Furthermore, TRPs induced transient
      increases in protein phosphorylation mediated by protein kinase C and protein
      tyrosine phosphorylation, whereas these same responses to thrombin were greater
      and more sustained. Hirudin added after thrombin accelerated protein
      dephosphorylation, thereby mimicking the rate of spontaneous dephosphorylation
      seen after stimulation by TRPs. Platelets totally desensitized to very high
      concentrations of TRPs, by prior exposure to maximally effective concentrations
      of the peptides, remained responsive to alpha- and gamma-thrombins. Thrombin
      stimulated PtdOH production in permeabilized platelets desensitized to TRPs was
      abolished by guanosine 5'-[beta-thio]diphosphate (GDP[beta S]), as in normal
      platelets. These results are discussed in terms of the allosteric Ternary Complex
      Model for G-protein linked receptors [Samama et al. (1993) J. Biol. Chem. 268,
      4625-4636]. We conclude that: (1) TRPs are partial agonists for the thrombin
      receptor and produce incomplete receptor desensitization in keeping with their
      lower intrinsic activity; (2) thrombin's effects in platelets, even in TRP
      desensitized platelets, are entirely mediated through the recently cloned G
      protein linked receptor, and (3) thrombin's ability to produce sustained signals,
      compared with TRPs, may require the continued progressive proteolytic activation
      of naive thrombin receptors.

PMID- 7526840
TI  - Inhibition of adenylate cyclase activity by galanin in rat insulinoma cells is
      mediated by the G-protein Gi3.
AB  - Galanin inhibits adenylate cyclase activity and insulin secretion and modulates
      ion channels in pancreatic beta-cells through pertussis-toxin-sensitive G
      protein(s). Antibodies directed against the C-terminal region of specific G
      protein alpha-subunits were used to determine which G-protein(s) couple galanin
      receptors to inhibition of adenylate cyclase in the rat insulinoma cell line
      RINm5F. Preincubation of membranes with EC antibody (anti-alpha i3) decreased the
      inhibition of forskolin-stimulated adenylate cyclase activity by galanin (100 nM)
      by 45% compared with control IgG (P < 0.05) whereas preincubation with AS (anti
      alpha i1, alpha i2) or GO (anti-alpha o) antibodies had no significant effect. To
      confirm these results, RINm5F cells were exposed intermittently over a 4-day
      period to phosphorothioate oligodeoxynucleotides that were either sense or
      antisense to alpha i1, alpha i2, alpha i3 or alpha o. Oligodeoxynucleotides
      antisense to alpha i2, alpha i3 and alpha o specifically decreased the levels of
      the targeted alpha-subunit in membranes. alpha i1 was undetectable in these
      cells. Inhibition of adenylate cyclase activity by galanin was largely abolished
      in membranes from cells exposed to the oligodeoxynucleotide antisense to alpha
      i3, whereas all other oligodeoxynucleotides had no significant effect on this
      pathway. Indirect immunofluorescence and immunoblotting of specific membrane
      fractions with EC antibody show significant localization of alpha i3 to
      intracellular membrane compartments. These results suggest that Gi3 is the G
      protein that couples galanin receptors to inhibition of adenylate cyclase
      activity in RINm5F cells.

PMID- 7526844
TI  - Possible role of protein kinase C-epsilon isoenzyme in inhibition of interleukin
      1 beta induction of nitric oxide synthase in rat renal mesangial cells.
AB  - In cultured glomerular mesangial cells, interleukin 1 beta (IL-1 beta) has been
      shown to induce a dose- and time-dependent accumulation of nitrite, a stable
      metabolite of nitric oxide (NO). In parallel, increased levels of mRNA of an
      inducible macrophage-type of nitric oxide synthase (iNOS) were observed after
      incubating mesangial cells with IL-1 beta. Here we report that addition of the
      biologically active phorbol esters, phorbol 12-myristate 13-acetate (PMA) and
      phorbol 12,13-dibutyrate (PDBu), dose-dependently inhibited the IL-1 beta
      stimulated increase in iNOS mRNA levels and nitrite production. In contrast, the
      biologically inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate, had no
      effect on cytokine induction of iNOS and nitrite formation. Incubation of
      mesangial cells with PMA or PDBu alone, in the absence of IL-1 beta, did not
      trigger any iNOS expression. Time-course studies indicated that phorbol ester
      needs to be added for only 1 h in order to maximally inhibit cytokine-induced
      nitrite production. Down-regulation of protein kinase C (PKC)-alpha and -delta
      isoenzymes by 8 h PMA or PDBu treatment before stimulation with IL-1 beta still
      resulted in full inhibition of iNOS induction. In contrast, a 24 h treatment of
      mesangial cells with PMA or PDBu, a regimen that also causes depletion of PKC
      epsilon, abolished inhibition of IL-1 beta-induced iNOS expression and nitrite
      production. In addition, the selective PKC inhibitor calphostin C potentiated IL
      1 beta induction of iNOS activity. In summary these data suggest that IL-1 beta
      induction of iNOS expression is tonically suppressed by PKC and the epsilon
      isoenzyme is the most likely candidate mediating this effect.

PMID- 7526845
TI  - Two sites on P-selectin (the lectin and epidermal growth factor-like domains) are
      involved in the adhesion of monocytes to thrombin-activated endothelial cells.
AB  - P-selectin, also known as GMP-140, PADGEM or CD62, is expressed on the surface of
      thrombin-activated platelets and endothelial cells (EC). It is a member of the
      selectin family of adhesion molecules that regulate leucocyte interactions with
      the blood vessel wall. In this study we have found that peptides derived from
      both the lectin (residues 19-34 and 51-61) and epidermal growth factor (EGF)-like
      (residues 127-139) domains inhibit the adhesion of peripheral blood mononuclear
      cells (PBMC), elutriated monocytes and a monocytic cell line (U937) to thrombin
      activated EC. This inhibition occurred in a concentration-dependent manner and
      the peptide most active at the lowest concentrations was the one derived from the
      EGF-like motif (127-139). The scrambled forms of these peptides, identical in
      amino acid composition to the authentic peptides but with altered sequences, were
      not inhibitory. Thrombin-activated platelets supported adhesion of U937 cells and
      this adhesion was dramatically inhibited by the two peptides derived from the
      lectin-like domain (residues 19-34 and 51-61). All three peptides, when
      conjugated to BSA and coated on plastic plates, mediated U937 cell adhesion. This
      study shows, for the first time, that two sites on P-selectin, the lectin and EGF
      like domains, are involved in the adhesion of monocytes to thrombin-activated EC.

PMID- 7526842
TI  - Rapid stimulation of mitogen-activated protein kinase of rat liver by prolactin.
AB  - Intraperitoneal prolactin administration to female rats caused a rapid and
      transient stimulation of hepatic mitogen-activated kinase (MAP kinase) activity
      measured in vitro as cytosolic phosphotransferase capacity towards two specific
      substrates. Myelin basic protein kinase activity of MAP kinase immunoprecipitates
      confirmed the specificity and magnified the prolactin effect. Immunoblot
      experiments with anti-(MAP kinase) and anti-phosphotyrosine antibodies showed
      changes in both electrophoretic mobility and phosphotyrosine content of 40 and 44
      kDa isoenzymes suggesting that prolactin affects these isoforms. Concomitant with
      the increase in MAP kinase activity, prolactin induced tyrosine phosphorylation
      in a number of liver proteins, suggesting a rapid involvement of tyrosine kinases
      which might be correlated in some way with MAP kinase activation. Protein kinase
      C activity, which has been implicated in the regulation of MAP kinase and in
      mediating the prolactin effect, does not seem to participate in MAP kinase
      activation.

PMID- 7526843
TI  - Annexin 3 is associated with cytoplasmic granules in neutrophils and monocytes
      and translocates to the plasma membrane in activated cells.
AB  - Annexins are soluble proteins capable of binding to phospholipid membranes in a
      calcium-dependent manner. Annexin 3, a 33 kDa protein mainly expressed in
      neutrophils, aggregates granules in cell-free assays, and a 36 kDa variant of
      this protein, specifically expressed in monocytes, has recently been identified.
      To obtain further information on these proteins, we defined their subcellular
      localization in resting and activated cells by immunofluorescence microscopy.
      Both proteins were associated with cytoplasmic granules in resting cells. We
      obtained evidence to indicate that, in neutrophils which possess a heterogenous
      granule population, annexin 3 was more likely to be associated with the specific
      granules. In cells activated with phorbol 12-myristate 13-acetate or opsonized
      zymosan, the 33 kDa and 36 kDa proteins translocated to the plasma or the
      phagosome membrane. Upon stimulation with A23187, annexin 3 translocated to the
      plasma membrane only in neutrophils. We also report that while annexin 3 was
      associated with restricted membranes in intact cells, it binds indiscriminately
      to every membrane fraction in cell-free assay. In conclusion, association of both
      forms of annexin 3 with granules suggests that these proteins could be implicated
      in processes of granule fusion.

PMID- 7526846
TI  - Induction of the FK506-binding protein, FKBP13, under conditions which misfold
      proteins in the endoplasmic reticulum.
AB  - In order to determine whether the endoplasmic reticulum (ER) luminal FK506
      binding protein, FKBP13, shares properties of ER molecular chaperones, MDCK cells
      were treated with either tunicamycin or Ca2+ ionophores. By Northern-blot
      analysis, tunicamycin resulted in a 2-fold rise in FKBP13 mRNA, whereas
      ionophores (A23187 and ionomycin) caused a more impressive rise in FKBP13 mRNA
      (up to 5-fold with ionomycin). Actinomycin D chase experiments in ionomycin
      treated cells revealed no change in the half-life of FKBP13 mRNA, indicating that
      the increase in FKBP13 mRNA observed was not due to greater message stability.
      Moreover, sequencing of the 5' flanking region of the gene for murine FKBP13
      revealed significant similarity to similar regions in human BiP (immunoglobulin
      binding protein) and the human glucose-regulated protein grp94, including a 37 bp
      sequence in FKBP13 with approximately 50% identity with the unfolded protein
      response element of the BiP gene. Together, these data suggest a role for FKBP13
      in ER protein folding.

PMID- 7526847
TI  - Characterization of platelet-activating factor binding to human airway epithelial
      cells: modulation by fatty acids and ion-channel blockers.
AB  - Radioligand-binding studies were performed in primary cultured human airway
      epithelial cells with [3H]PAF to determine whether these cells express platelet
      activating factor (PAF) receptors. Scatchard analysis of PAF binding data
      revealed a single class of PAF binding sites with Kd 1.8 +/- 0.2 nM and Bmax.
      21.0 +/- 2.1 fmol/10(6) cells (13,000 receptors/cell). PAF binding increased the
      intracellular free Ca2+ concentration ([Ca2+]i), indicating functional PAF
      receptors. Palmitate (C16:0), linoleic acid (C18:2 omega 6) or eicosapentaenoic
      acid (C20:5 omega 3) was incubated with the cells to test the effect on PAF
      binding. Incorporation of each fatty acid into cellular phospholipid occurred.
      [3H]PAF (1 nM) binding decreased in cells supplemented with C20:5 omega 3, but
      increased in the cells supplemented with C16:0. Scatchard analysis revealed that
      the inhibition of PAF binding by supplementation with C20:5 omega 3 was due to a
      decrease in both affinity and number of PAF receptors. PAF-stimulated increase in
      [Ca2+]i was also decreased by 60% in cells supplemented with C20:5 omega 3.
      Verapamil, a Ca(2+)-channel blocker, and amiloride, a Na(+)-channel blocker,
      inhibited specific binding of [3H]PAF to the cells, with IC50 4-5 microM and 0.2
      mM respectively. Diphenylamine-2-carboxylate (DPC), a Cl(-)-channel blocker,
      dramatically increased PAF binding to the cell in a dose-dependent manner.
      Scatchard analysis revealed that verapamil and amiloride decreased both binding
      affinity and number of PAF receptors, whereas DPC increased PAF binding sites
      without affecting binding affinity. These results demonstrate that human airway
      epithelial cells have a functional receptor for PAF and that PAF receptor binding
      can be modulated by exogenous fatty acids and by ion-channel blockers.

PMID- 7526849
TI  - Regulation of cytosolic calcium and insulin secretion by galanin and ATP
      receptors: interactions of pertussis-toxin-sensitive and -insensitive signalling
      pathways.
AB  - In a previous study it was found that the expression of the exogenous fMet-Leu
      Phe-receptor (NFPR) in the insulin-secreting cell line RINm5F mediates inhibition
      of hormone release and additionally raises cytosolic calcium concentration
      ([Ca2+]i) by activating phospholipase C (PLC) in a pertussis-toxin (PTX)
      sensitive manner. We investigated whether an endogenous receptor could elicit
      similar effects and examined the interaction with PTX-insensitive signalling
      pathways. The hormone galanin inhibited insulin release at subnanomolar
      concentrations and increased [Ca2+]i, mainly by a PTX-sensitive mechanism with an
      EC50 (50 nM) comparable with that for hyperpolarization of membrane potential.
      The effect of galanin or fMet-Leu-Phe on [Ca2+]i was inhibited by pre-activation
      of the P2-receptor by ATP, which mobilizes calcium in a PTX-insensitive fashion.
      Simultaneous activation of the P2- and peptide receptors caused additive
      increases in [Ca2+]i saturating at a calcium concentration corresponding to the
      optimal ATP response. This suggests a specific convergence of PTX-sensitive and 
      insensitive pathways. In contrast, galanin and FMLP inhibited the insulin
      secretion induced by ATP (1-100 microM), but only when added prior to the
      nucleotide. In permeabilized cells, FMLP added after the calcium stimulus still
      inhibited secretion, indicating that the inefficacy observed in intact cells was
      not due to the rapid ATP-evoked rise in [Ca2+]i. Thus, (i) insulin-secreting
      cells possess an endogenous PTX-sensitive pathway mobilizing [Ca2+]i, (ii)
      inhibitory hormones preferentially activate different effectors depending on the
      agonist concentration and (iii) activation of NFPR or galanin receptor reveals an
      unusual dissociation between [Ca2+]i rises and insulin secretion, pointing
      towards an overriding inhibitory control of exocytosis.

PMID- 7526848
TI  - Different zonal distribution of the asialoglycoprotein receptor, the alpha 2
      macroglobulin receptor/low-density-lipoprotein receptor-related protein and the
      lipoprotein-remnant receptor of rat liver parenchymal cells.
AB  - Periportal and perivenous parenchymal cells were isolated by the digitonin-pulse
      perfusion method. The digitonin-pulse perfusion was shown to lead to selective
      lysis of the correct zone with a straight and sharp border of two to three cells.
      The mean ratios of alanine aminotransferase activity (a marker for periportal
      parenchymal cells) and glutamine synthetase activity (a perivenous marker) of
      periportal to perivenous parenchymal cells were 1.76 and 0.025 respectively.
      Cells were incubated in vitro with 125I-asialo-orosomucoid (ASOR), 125I-trypsin
      activated alpha 2-macroglobulin (alpha 2M-T) or 125I-beta-migrating very-low
      density lipoprotein (beta-VLDL), in order to determine the zonal distribution of
      the asialoglycoprotein receptor (ASGPr), the alpha 2-macroglobulin receptor/low
      density-lipoprotein receptor-related protein (alpha 2Mr/LRP) and the lipoprotein
      remnant receptor, respectively. Maximum binding capacity for 125I-ASOR on
      parenchymal cells showed a periportal/perivenous ratio of 0.70. The
      periportal/perivenous ratio of Bmax. values of binding of 125I-alpha 2M-T to
      parenchymal cells was 1.51. The Bmax. values of binding of 125I-beta-VLDL,
      however, were about equal for both cell populations. It is concluded that the
      maximum binding capacity of the ASGPr on isolated periportal parenchymal cells is
      0.70 times that of perivenous parenchymal cells. The 1.51-fold higher expression
      of the alpha 2Mr/LRP on periportal cells, compared with perivenous parenchymal
      cells, indicates a zonal specialization for the uptake of the suggested multiple
      ligands. In contrast, the observed homogeneous distribution of the lipoprotein
      remnant receptor is in accordance with the suggestion that lipoprotein remnants
      bind to a specific receptor, which is different from the alpha 2Mr/LRP. The zonal
      heterogeneity in the expression of receptors suggests that receptor-dependent
      uptake pathways are under zonal control, leading to intrahepatic heterogeneity in
      the removal of ligands from the blood circulation.

PMID- 7526850
TI  - Human erythrocyte ankyrin, a cytoskeleton component, generates the p57 membrane
      proteinase which cleaves C3, the third component of complement.
AB  - Human erythrocytes express a p57 membrane serine proteinase which cleaves C3, the
      third component of complement. Amino acid analysis of the first 20 N-terminal
      residues of the purified p57 proteinase demonstrated 100% homology with residues
      910-929 of erythrocyte ankyrin, a sequence localized in its Mr = 62 kDa fragment.
      Thus, we analyzed whether ankyrin could generate the p57 C3-cleaving activity. We
      demonstrate herein that: 1) anti-ankyrin antibodies react with purified p57
      proteinase; 2) anti-p57 proteinase antibodies react with purified ankyrin but not
      with spectrin, another cytoskeleton component; 3) while purified ankyrin did not
      carry any detectable proteinase activity, limited proteolysis of ankyrin by
      immobilized chymotrypsin generated this C3-cleaving serine proteinase. Spectrin
      did not generate any C3-cleaving activity. This is the first demonstration that
      erythrocyte ankyrin could generate a proteinase activity, which in addition,
      cleaves specifically human C3.

PMID- 7526851
TI  - Inhibition of nitric oxide synthesis enhances the expression of inducible nitric
      oxide synthase mRNA and protein in a model of chronic liver inflammation.
AB  - In septic shock the inhibition of inducible nitric oxide synthase (iNOS) could be
      of therapeutic value. However, side effects have to be investigated. Therefore we
      studied the effects of chronic NOS inhibition on the level of iNOS expression in
      a model of chronic liver inflammation induced by Corynebacterium parvum (C.
      parvum) which causes sustained iNOS expression in the liver. NOS inhibitors
      decreased the rise in plasma levels and urinary excretion of nitrite/nitrate by
      about 50%; however, iNOS mRNA and protein were increased to 200% and 150%,
      respectively. Thus chronic inhibition of NOS can result in an increase in iNOS
      mRNA level and protein under conditions when iNOS is expressed. This could result
      in an overproduction of NO upon removal of the NOS-inhibitor.

PMID- 7526852
TI  - CFTR protein is involved in the efflux of neutral amino acids.
AB  - Trans-membrane fluxes of leucine were measured in mouse C127i cells transfected
      with the wild type (C127 CFTRw/t) or the delta F508 CF gene (C127 CFTR delta
      F508). Leucine efflux was significantly faster in C127 CFTRw/t cells. On the
      contrary, leucine influx was comparable in the two cell lines and referable to a
      "L-type" transport system. No significant differences in leucine content were
      detected among the two cell lines when maintained in complete growth medium; in
      contrast, after prolonged incubation in amino-acid-free saline solution, the
      amount of intracellular leucine was significantly smaller in C127 CFTRw/t than in
      C127 CFTR delta F508 cells. Leucine behavior was shared by other neutral amino
      acids with non polar side chains. These results suggest that the expression of
      normal CFTR increases the efflux of a subgroup of neutral amino acids.

PMID- 7526854
TI  - Molecular and functional analysis of porcine E-selectin reveals a potential role
      in xenograft rejection.
AB  - In this study, we report the molecular and functional characterization of porcine
      E-selectin. Incubation of porcine endothelial cells with human TNF alpha but not
      human IL-1 resulted in a marked increase in binding to human neutrophils. In
      order to confirm that this interaction was mediated by E-selectin, we isolated
      the full-length porcine E-selectin cDNA which contained an open reading frame
      encoding 485 amino acids with 75% identity to human E-selectin. Expression or
      recombinant porcine E-selectin in COS cells resulted in surface expression of the
      protein and increased binding to human neutrophils. Northern blot analysis showed
      that treatment of porcine endothelial cells with human TNF alpha but not human IL
      1 resulted in high levels of porcine E-selectin mRNA. Taken together, our data
      establish that porcine E-selectin mediates adhesive interactions between porcine
      endothelial cells and human leukocytes that may contribute to xenograft
      rejection.

PMID- 7526853
TI  - Endotoxin causes reciprocal changes in hepatic nitric oxide synthesis,
      gluconeogenesis, and flux through phosphoenolpyruvate carboxykinase.
AB  - Treatment of rats with bacterial endotoxin resulted in a significant induction of
      hepatic nitric oxide synthase within 3 hours. The response was maximal at 12
      hours and was maintained over 18 hours. The induction of nitric oxide synthase
      correlated well with the increase in plasma nitrate plus nitrite concentrations
      and also with the inhibition of glucose synthesis in subsequently isolated
      hepatocytes. The decline in the rate of gluconeogenesis also correlated with an
      inhibition of flux through phosphoenolpyruvate carboxykinase but not with
      alterations in flux through either pyruvate kinase or 6-phosphofructo-1-kinase,
      suggesting that a nitric oxide-induced inhibition of phosphoenolpyruvate
      carboxykinase may underlie the decreased glucose production in sepsis.

PMID- 7526855
TI  - Cloning of a novel cDNA homologous to CHIP28 water channel from ocular ciliary
      epithelium.
AB  - Water channel protein (CHIP28) has been initially identified from human
      erythrocyte and subsequently localized in human kidney, rat kidney and bovine
      corneal endothelium. We report here cloning of homologous cDNA (CHIP29) from an
      expression cDNA library constructed from bovine ciliary epithelium poly A+ that
      codes a 271 amino acid, 28.8 kDa protein. At the amino acid level, bovine CHIP29
      is 91% identical to the CHIP28 protein. Analysis of the deduced amino acid
      sequence indicated a hydrophobic protein with six membrane spanning domains, one
      N-linked glycosylation site, two conserved NPA boxes common to MIP26 family
      proteins, and conserved amino acid residue cysteine 189 common to water channels.
      Northern blotting revealed a major mRNA of 2.8 Kb size expressed in bovine
      ciliary epithelium. The results presented here confirm the presence of water
      channel gene in the bovine ciliary epithelium, a primary site for the aqueous
      humor production.

PMID- 7526856
TI  - 2-Iminobiotin is an inhibitor of nitric oxide synthases.
AB  - Nitric oxide synthase (NOS, EC 1.14.23) catalyzes the oxidation of the guanidino
      nitrogen of L-arginine to form nitric oxide and L-citrulline. 2-Iminobiotin was
      found to be a reversible inhibitor of murine iNOS and rat n-cNOS with Ki values
      of 21.8 and 37.5 microM, respectively. The urea and thiourea analogs, biotin and
      thiobiotin, were not inhibitors of NOS, indicating that the guanidino group of 2
      iminobiotin is essential for binding. 2-iminobiotin carboxy derivatives were also
      inhibitors of iNOS which indicates that the free carboxyl group is not required
      for binding. 2-Iminobiotin is a novel, potent inhibitor of NO biosynthesis and
      may be a useful reagent in the understanding of binding-site interactions for
      this important class of enzymes.

PMID- 7526857
TI  - A crucial effect of ligand clustering on the inhibition of binding by L-selectin
      in intercellular adhesion.
AB  - Glucan sulfates were found to be potent ligands for L-selectin by a quantitative
      liquid phase analysis system (Yoshida, T. et al., Eur. J. Biochem., in press).
      The affinity of glucan sulfates to L-selectin-IgG chimera was dependent on the
      size of the glucan sulfates as well as on the inter-glucose linkages. In the
      current report, these glucan sulfates are shown to inhibit the interaction of an
      endothelial cell line with lymphocytes. The effect of ligand size appears to be
      more remarkable in the cell-cell binding than in the liquid phase analysis. The
      affinity of amylose sulfate continues to increase, as their size increases even
      beyond 12 kDa, at which its affinity reached a plateaux in the liquid phase
      analysis.

PMID- 7526858
TI  - Identification of a meta-cleavage pathway for metabolism of phenoxyacetic acid
      and phenol in Pseudomonas cepacia AC1100.
AB  - Pseudomonas cepacia strain AC1100 grows luxuriantly on 2,4,5
      trichlorophenoxyacetic acid (2,4,5-T) but does not utilize phenoxyacetic acid.
      After long-term selective pressure on phenoxyacetic acid, mutants designated as
      strain PAA, capable of utilizing phenoxyacetic acid as well as phenol, emerged
      spontaneously at a frequency of 1 x 10(-8). A deletion mutant strain PT88, which
      is devoid of a part of 2,4,5-T metabolic pathway, generated neither phenoxyacetic
      acid utilizing nor phenol-utilizing mutants. The wild type (Wt) strain AC1100 and
      all its mutants utilized benzoate via ortho-cleavage pathway. However, only
      mutant strain PAA harbored the whole set of enzymes required for utilization of
      phenol via meta-cleavage pathway. The results suggest that Wt strain AC1100
      carries silent genes for meta-cleavage pathway which are expressed in strain PAA
      enabling it to utilize phenoxyacetic acid and phenol. Gene activation is presumed
      to be due to the translocation of insertion elements.

PMID- 7526859
TI  - Apoptosis in L929 cells expressing a CD40/Fas chimeric receptor: dissociation of
      stimulatory from inhibitory death signalling functions.
AB  - A chimeric transmembrane receptor was constructed by fusing the extracellular
      domain of human CD40 to the transmembrane/intracellular domain of human Fas. When
      stably overexpressed in L929, the chimera retained the ligand binding specificity
      of CD40 and the basic signalling properties of Fas since an apoptotic response
      could be induced in a dose-dependent manner upon administration of recombinant,
      soluble CD40 ligand trimer or immobilized antiCD40 antibodies. However, this
      apoptotic response was independent of actinomycin D which is in contrast to
      results previously reported for L929 cells stably expressing wildtype human Fas.
      A labile protein factor was postulated to be responsible for inhibition of Fas
      induced apoptosis in these cells. The apoptotic Fas signal tranduced by the
      chimeric CD40/Fas receptor is not regulated by this putative inhibitor. Our data
      suggest that the extracellular domains of CD40 and Fas form functionally similar
      mono- and multimeric structures and that the extracellular domain of Fas
      participates in the regulation of Fas-specific signal transduction.

PMID- 7526864
TI  - The 3'-untranslated region of mouse myelin basic protein gene increases the
      amount of mRNA in immortalized mouse oligodendrocytes.
AB  - The 3'-untranslated region (UTR) of the myelin basic protein (MBP) mRNA has been
      found previously to enhance the translational efficiency of the coding region by
      two-fold in cell-free translational systems. In this study, we transfected
      eukaryotic expression vectors containing the reporter cDNA for chloramphenicol
      acetyltransferase (CAT) with or without the mouse MBP cDNA 3'-UTR into cultured
      cells. CAT activity in the mouse oligodendrocyte cell line, N20.1, transfected
      with a CAT cDNA containing the MBP 3'-UTR [CAT-MBP 3'-UTR], was twice as high as
      that of the CAT cDNA without the 3'-UTR; CAT activities for the two constructs
      were the same in the mouse fibroblast cell line, NIH 3T3. Using reverse
      transcriptase PCR quantitative analysis, the expression of mRNA was determined.
      The level of the [CAT-MBP 3'-UTR] mRNA was about ten times higher than CAT mRNA
      in N20.1 cells but they were the same in NIH 3T3 cells. We conclude that the 3'
      UTR of MBP gene increases gene expression at both the mRNA and protein levels in
      oligodrocyte cell lines, probably through a post-transcriptional mechanism such a
      message stabilization.

PMID- 7526861
TI  - Modeling of prostate specific antigen and human glandular kallikrein structures.
AB  - The three dimensional structures of human prostate specific antigen (PSA) and
      glandular kallikrein (hGK) were modeled based on porcine pancreatic kallikrein A.
      High sequence similarity and conserved framework of serine proteases enabled
      accurate modeling. The catalytic site region consisting of catalytic triad,
      residues forming oxyanion hole and main-chain substrate binding residues were
      conserved. The substrate specificity pocket of PSA resembles that of chymotrypsin
      and hGK is most related with tonin. The models were used to predict interactions
      with substrate and inhibitor molecules. The models are valuable in interpreting
      mutant and epitope mapping data as well as when modifying properties of the
      proteases or when developing diagnostic detection methods for prostatic cancer.

PMID- 7526863
TI  - Phorbol ester activation of protein kinase C inhibits CNP-stimulated cyclic GMP
      production in the mouse AtT-20 pituitary tumour cell line.
AB  - Preincubation of AtT-20 mouse pituitary tumour cells with the phorbol ester PMA
      resulted in a concentration-dependent inhibition of CNP-stimulated cyclic GMP
      production. The phorbol ester analogue 4 alpha phorbol had no inhibitory effect
      and 24 h preincubations with PMA resulted in a characteristic down-regulation of
      the response indicating that the inhibitory actions were mediated via the
      activation of protein kinase C. Forskolin in the presence of the
      phosphodiesterase inhibitor IBMX stimulated intracellular cyclic AMP
      concentrations by up to eight fold, but did not alter basal nor CNP-stimulated
      cyclic GMP production. These results indicate that CNP-stimulated guanylate
      cyclase activity associated with the GC-B natriuretic peptide receptor expressed
      in AtT-20 cells is inhibited by protein kinase C.

PMID- 7526862
TI  - Interactions of atrial natriuretic peptide with A7r5 cells.
AB  - The interactions of Atrial Natriuretic Peptide with its receptors were
      investigated with the vascular smooth muscle cells from the A7r5 cell line.
      Displacement experiments of [125I]rat-Atrial Natriuretic Peptide by rat-Atrial
      Natriuretic Peptide revealed a single class of receptors with a Kd = 0.21 +/-
      0.08 nM and a Bmax = of 35 +/- 16 fmol/mg of protein. Furthermore, the complex
      [125I]r-Atrial Natriuretic Peptide was internalised by a heatsensitive process.
      Finally, Atrial Natriuretic Peptide increased cyclic Guanosyl 3',5' Mono
      Phosphate in a time dependent and dose dependent way, a concentration of 0.1
      microM increasing cyclic Guanosyl 3',5' Mono Phosphate level by a factor of 8.3
      times when compared to basal level.

PMID- 7526865
TI  - Hepatocyte growth factor up-regulates met expression in rat fetal hepatocytes in
      primary culture.
AB  - Hepatocyte growth factor (HGF) is a potent mitogen for primary cultured fetal
      hepatocytes. In the present study, we have analyzed the c-met/HGF receptor
      expression in fetal hepatocytes and its modulation by growth factors and
      hormones. 20-day old fetal liver showed a barely expression of c-met mRNA levels.
      However, when fetal hepatocytes were incubated in the presence of HGF, a 10-fold
      increase in c-met mRNA levels was observed 30 min after addition of the factor.
      This HGF-induced effect on c-met expression was transient, losing its up
      regulatory effect after 24 hours and returning to the initial levels at 48 hours.
      Transforming growth factor-beta, a negative regulator of fetal liver growth,
      increased c-met mRNA levels 48 hours after the addition of the factor, whereas
      glucocorticoids had a negative effect.

PMID- 7526860
TI  - Keratinocyte growth factor and acidic fibroblast growth factor are mitogens for
      primary cultures of mammary epithelium.
AB  - Mammary epithelial cells derived from the entire mammary parenchyma or only end
      buds were isolated by collagenase digestion of mammary glands from virgin mice.
      Cells were cultured within collagen gels in serum-free medium containing insulin.
      Keratinocyte growth factor (KGF or FGF-7) and acidic fibroblast growth factor
      (aFGF or FGF-1) stimulated multifold proliferation when added alone to this
      medium. Growth occurred as three-dimensional colonies within the collagen gel
      matrix. KGF stimulated growth was unaffected by adding heparin. Conversely,
      multifold growth stimulation by acidic FGF required heparin. Since end buds are
      the actively proliferating cell population of ductal glands, organ cultures of
      these structures were prepared. KGF stimulated 3H-thymidine incorporation in
      these end buds in the absence and presence of epidermal growth factor. These data
      suggest that acidic FGF and KGF may represent in vivo stromal factors capable of
      regulating mammary gland development.

PMID- 7526868
TI  - Elevated cerebrospinal fluid levels of substance P in patients with the
      fibromyalgia syndrome.
AB  - OBJECTIVE: To measure, and seek clinical correlates with, levels of substance P
      (SP) in the cerebrospinal fluid (CSF) of fibromyalgia syndrome (FMS) patients.
      METHODS: CSF from 32 FMS patients and 30 normal control subjects was tested for
      SP by radioimmunoassay. Clinical measures included tender point examination and
      standardized questionnaires. RESULTS: CSF SP levels were 3-fold higher in FMS
      patients than in normal controls (P < 0.001), but they correlated only weakly
      with tenderness found on examination. CONCLUSION: SP is significantly elevated in
      FMS CSF, but other abnormalities must exist in FMS to more fully explain the
      symptoms.

PMID- 7526866
TI  - Role of ATP and sodium in polyamine transport in bovine pulmonary artery smooth
      cells.
AB  - Increased polyamine transport may be a key mechanism driving elevations in lung
      cell polyamine content necessary for the development of chronic hypoxic pulmonary
      hypertension. Bovine pulmonary artery smooth muscle cells (PASMCs) in culture
      exhibit two carriers for polyamines, a non-selective one shared by the three
      polyamines, putrescine (PUT), spermidine (SPD), and spermine (SPM), and another
      that is selective for SPD and SPM. Hypoxia appears to up-regulate both carriers.
      In this study, we examined the role of ATP and the Na+ gradient in regulating
      polyamine transport in control PASMCs and in PASMCs with polyamine transport
      augmented by culture under hypoxic conditions (Po2: 15-30 torr). Inhibition of
      ATP synthesis with dinitrophenol+iodoacetate profoundly reduced polyamine uptake
      in both control and hypoxic PASMCs. Putrescine uptake was somewhat more sensitive
      to iso-osmotic replacement of extracellular Na+ with choline chloride or sucrose
      than were SPD or SPM in both hypoxic and standard cells, but under no conditions
      did Na+ replacement substantially alter polyamine uptake. Treatment of PASMCs
      with ouabain, a Na(+)-K+ ATPase inhibitor, or with gramicidin, a Na+ ionophore,
      minimally attenuated polyamine transport, whereas the Na+/K+ ionophore monensin
      increased polyamine uptake in standard, but not in hypoxic, cells. In general,
      the reduction in the extracellular Na+ content or ionophore-induced increases in
      Na+ permeability had a greater suppressive effect on polyamine transport in
      hypoxic cells than in standard cells, suggestive of the induction of Na(+)
      dependent polyamine carriers by hypoxia. These observations indicate that the
      activities of the two putative polyamine transport pathways in standard PASMCs,
      as well as their up-regulation by hypoxia, require ATP synthesis. In addition, it
      appears that polyamine transport in PASMCs is composed of two components: one a
      prominent sodium-independent transporter and the other a relatively minor
      component that is sodium dependent. The latter may be activated by hypoxic
      exposure in combination with the induction of new polyamine carriers.

PMID- 7526867
TI  - Multiple mechanisms of arachidonic acid release in Chinese hamster ovary cells
      transfected with cDNA of substance P receptor.
AB  - We investigated the release of [3H]arachidonic acid ([3H]AA) and its relationship
      to the formation of [3H]inositol trisphosphate ([3H]IP3) elicited by substance P
      (SP) in prelabeled Chinese hamster ovary cells stably expressing the SP receptor.
      Activation of the SP receptor resulted in a concentration- and time-dependent
      stimulation of [3H]AA release. Half-maximal release was obtained at 10(-9) M,
      comparable to that for [3H]IP3 formation reported previously, and the maximal
      release effected by 0.1 microM SP was 8 to 10-fold above the basal value. Both
      the [3H]AA release and the [3H]-IP3 accumulation stimulated in the cells by 0.1
      microM SP were concentration-dependently blocked with the specific SP receptor
      antagonist CP-96,345, with IC50 values of 2.5 and 0.4 microM, respectively. The
      time course of [3H]AA release showed a biphasic pattern: an initial rapid release
      essentially independent of Ca2+, followed by a sustained release markedly
      suppressed by removal of extracellular Ca2+ or chelation of intracellular Ca2+
      with 1,2-bis(2-aminophenoxyethane)-N,N,N',N'-tetraacetic acid (BAPTA). While
      pretreatment with pertussis toxin (200 ng/mL, 6 hr) did not block [3H]IP3
      formation, it did reduce [3H]AA release by 50% at 1 and 10 min after SP
      stimulation. Treatment of the cells with a phorbol ester, a protein kinase C
      activator, augmented the SP-stimulated [H]AA release, and sphingosine, a protein
      kinase C inhibitor, reversed the phorbol ester-potentiated [3H]AA release, but
      not the release stimulated by SP alone, suggesting a synergistic effect of
      protein kinase C on SP-stimulated AA release. These results demonstrate that SP,
      acting at the SP receptor, stimulates [3H]AA release via mechanisms that are (1)
      mediated by a pertussis toxin-sensitive G-protein, (2) dependent on extracellular
      Ca2+, and (3) enhanced by activation of protein kinase C.

PMID- 7526870
TI  - A new model for rheumatoid arthritis generated by engraftment of rheumatoid
      synovial tissue and normal human cartilage into SCID mice.
AB  - OBJECTIVE: A new animal model was used to study the interaction between
      rheumatoid synovial cells and cartilage and to explore the cellular basis of
      rheumatoid joint destruction. METHODS: Fresh synovial tissue derived from
      patients with rheumatoid arthritis was implanted with normal human cartilage into
      SCID mice, either subcutaneously or under the renal capsule, for up to 304 days.
      The implants were analyzed by light and electron microscopy, as well as by
      immunohistochemistry and in situ hybridization. RESULTS: Human synovial tissue
      and cartilage implanted in SCID mice are maintained by the animals for up to 304
      days. After 35 days, focal erosions occur at the site of attachment of synovial
      lining cells to the cartilage. After 105 days, a pannus-like formation,
      consisting of proliferating synovial fibroblast-like cells invading the
      cartilage, is observed. The fibroblast nature of these cells was supported by
      observation of only focal expression of the macrophage markers CD14 and CD68.
      Cells at the immediate site of cartilage destruction express messenger RNA for
      cathepsin L, whereas cathepsin D messenger RNA was detected in subsynovial
      regions away from the site of destruction. The human origin of the tissue
      involved in cartilage destruction was demonstrated using monoclonal antibodies to
      HLA-ABC and human type IV collagen. CONCLUSION: The present approach introduces a
      novel in vivo model of rheumatoid arthritis for the study of the molecular and
      cellular mechanisms of rheumatoid joint destruction at sites of synovial
      attachment to cartilage. In this model, the SCID mouse acts as a useful host for
      studying the properties of rheumatoid synovium in the absence of circulating
      human blood components.

PMID- 7526871
TI  - Interferon-gamma-inducible protein p16. A new target of antinuclear antibodies in
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the cellular expression and localization of interferon
      gamma (IFN gamma)-inducible protein p16, a new antigen specificity of antinuclear
      antibodies (ANA), and to evaluate the prevalence of anti-p16, particularly in SLE
      patients. METHODS: Serum levels of anti-p16 were determined by immunoblotting
      with recombinant p16 and cellular p16 messenger RNA (mRNA) by Northern blotting.
      We also utilized immunoprecipitation of 35S-methionine-labeled proteins,
      immunostaining of blotted proteins of subcellular fractions, and
      immunofluorescence studies with affinity-purified rabbit and human anti
      recombinant p16. RESULTS: Protein p16 was localized within the nucleolus and
      nucleoplasm and constitutively expressed in Raji, HeLa, HEp-2, K562, and HL-60
      cells. Synthesis of mRNA and protein was increased in the presence of IFN gamma.
      The prevalence of anti-p16 was 29% in 374 SLE patients (35% in those positive for
      anti-double-stranded DNA) and 0% in 188 healthy individuals. Anti-p16 was always
      accompanied by positive findings on indirect immunofluorescence for ANA.
      CONCLUSION: Anti-p16 represents a main ANA specificity. Anti-p16 may help to
      elucidate IFN gamma-dependent nuclear processes and to link autoantibody
      production to states of IFN gamma activation.

PMID- 7526869
TI  - Elevated expression of CD80 (B7/BB1) and other accessory molecules on synovial
      fluid mononuclear cell subsets in rheumatoid arthritis.
AB  - OBJECTIVE: To assess the expression of important accessory molecules such as CD80
      (B7/BB1) and CD54 (intercellular adhesion molecule 1) on potential antigen
      presenting cells (APC) in the synovial fluid (SF) of patients with rheumatoid
      arthritis (RA). METHODS: The level of expression of various accessory molecules
      on T cells, monocytes, and CD5+ or CD5- B cells from RA SF was compared, by
      multiparameter flow cytometric analysis, with the expression on peripheral blood
      (PB) mononuclear cells from the same patients and from normal controls. The
      functional significance of increased expression of these accessory molecules was
      assessed by the ability of the different cell populations to stimulate T cells in
      the mixed lymphocyte reaction. RESULTS: Monocytes, T cells, and B cells isolated
      from the SF of inflamed joints of patients with RA expressed significantly higher
      levels of CD80 and CD54 than those from the PB of RA patients or normal controls.
      CD11b and CD11c expression also were increased on SF B cells, while SF monocytes
      exhibited enhanced levels of CD40. Further, we found that the elevated CD80 and
      CD54 levels in RA SF cells may enhance the capacity of these cells to act as
      stimulatory APC. CONCLUSION: This is the first demonstration that specific cell
      subsets constitutively express increased levels of CD80 at a site of autoimmune
      pathology, which could potentially contribute to the initiation or maintenance of
      autoimmune disease.

PMID- 7526872
TI  - Expression and shedding of intercellular adhesion molecule 1 and lymphocyte
      function-associated antigen 3 by normal and scleroderma fibroblasts. Effects of
      interferon-gamma, tumor necrosis factor alpha, and estrogen.
AB  - OBJECTIVE: To examine intercellular adhesion molecule 1 (ICAM-1) and lymphocyte
      function-associated antigen 3 (LFA-3) in cultures of normal and systemic
      sclerosis (SSc) dermal fibroblasts. METHODS: The surface and soluble forms of
      ICAM-1 and LFA-3 were measured by flow cytometry and capture enzyme-linked
      immunosorbent assay, respectively. RESULTS: Surface ICAM-1 was significantly
      higher on SSc fibroblasts compared with normal controls. Beta-estradiol did not
      directly enhance ICAM-1 or LFA-3 expression in either normal or SSc cells, but
      significantly augmented the cytokine-induced increase in ICAM-1. Soluble ICAM-1
      (sICAM-1) and sLFA-3 were detected in fibroblast cultures. While no difference
      was found in the level of sLFA-3, the shedding of sICAM-1 was significantly
      increased (P < 0.001) in cells from SSc patients. CONCLUSION: SSc fibroblasts
      express intrinsically elevated levels of surface ICAM-1 and release higher levels
      of sICAM-1 in vitro. Increased expression of ICAM-1 by interferon-gamma and tumor
      necrosis factor alpha alone, and the further induction in combination with beta
      estradiol may underlie an aspect of fibroblast dysfunction in SSc and the female
      predisposition to the disease.

PMID- 7526876
TI  - Assembly of humanized antibody genes from synthetic oligonucleotides using a
      single-round PCR.

PMID- 7526874
TI  - Prominent inhibitory effects of tranilast on migration and proliferation of and
      collagen synthesis by vascular smooth muscle cells.
AB  - To obtain some ideas about prevention of restenosis after percutaneous
      transluminal coronary angioplasty (PTCA), we examined the effects of transilast
      (anti-allergic agent) on migration and proliferation of, and collagen synthesis
      by, cultured vascular smooth muscle cells (VSMC) from the thoracic aorta of WKY
      rats. Tranilast was added to culture medium containing 10% fetal calf serum
      (FCS). The cultures were pulse-labeled with 3H-thymidine (TdR) or 3H-proline
      (Pro). TdR and Pro uptake into VSMC were measured. The effect of tranilast on
      migration of VSMC was examined by using culture dishes of an original design. We
      also examined the inhibitory effects of various drugs, such as a Ca antagonist,
      an angiotensin converting enzyme (ACE) inhibitor, a phosphodiesterase inhibitor,
      elastase, colchicine, and mitomycin C, on proliferation and migration of VSMC.
      Our data showed that the inhibitory effects of tranilast on migration and
      proliferation of, and collagen synthesis by, VSMC were prominent. Maximal
      percentage inhibition of proliferation, migration and collagen synthesis was 60.8
      +/- 2.3%, 52.7 +/- 14.7% and 62.1 +/- 8.1%, respectively. On the other hand, the
      inhibitory effects of other drugs, with the exception of colchicine and mitomycin
      C, on proliferation and/or migration of VSMC were not very strong. Although the
      inhibitory effects of colchicine and mitomycin C were strong in vitro, their
      clinical usefulness may be limited by systemic side-effects. These results
      indicate the potential usefulness of tranilast for prevention of restenosis of
      coronary arteries after PTCA.

PMID- 7526875
TI  - Involvement of adhesion molecules in human monocyte adhesion to and
      transmigration through endothelial cells in vitro.
AB  - Although the accumulation of monocyte-derived foam cells in the subendothelium is
      a key step in early atherogenesis, the mechanism responsible for monocyte
      adhesion to and subsequent transmigration through endothelial cells (ECs) has not
      been defined fully. We investigated the kinetics and the role played by adhesion
      molecules in the adhesion and transmigration of human monocytes using an in vitro
      three-dimensional model system comprising ECs cultured on collagen gels. Monocyte
      adhesion to untreated EC layers increased with time, reached a maximum after 3 h,
      and then declined. Monocyte transmigration through untreated EC layers also
      increased with time and reached a plateau after 3-4 h. Prestimulation of ECs with
      interleukin-1 beta (IL-1 beta; 25 U/ml) for 4 h enhanced monocyte adhesion (40.7
      +/- 1.4%) and transmigration (37.9 +/- 1.6%) significantly compared with the
      value for untreated EC layers. In unstimulated EC layers, anti-leukocyte function
      associated antigen-1 (LFA-1) plus anti-intercellular adhesion molecule-1 (ICAM-1)
      monoclonal antibodies (mAbs) inhibited monocyte adhesion and transmigration
      significantly by 19% and 20%, respectively, whereas anti-very late antigen-4 (VLA
      4) plus anti-vascular cell adhesion molecule-1 (VCAM-1) mAbs did not. In IL-1
      beta-stimulated EC layers, anti-LFA 1 plus anti-ICAM-1 mAbs inhibited the
      adhesion and transmigration by 32% and 30%, respectively and anti-VLA-4 plus anti
      VCAM-1 mAbs did so by 18% and 27%, respectively. These results suggest that the
      monocyte-EC interaction in unstimulated ECs is mediated, in part, by the LFA-1
      ICAM-1 pathway and in IL-1 beta-stimulated ECs, in part, by both LFA-1-ICAM-1 and
      VLA-4-VCAM-1 pathways.

PMID- 7526877
TI  - Enzymatic synthesis of milligram quantities of ribozymes in small volumes.
AB  - Milligram quantities of ribozymes (Rzs) can be synthesized in vitro in reaction
      volumes of 1 mL or less using AmpliScribe T7 RNA polymerase kits to transcribe
      either linear plasmids or oligodeoxynucleotide templates. Model hammerhead Rzs
      were synthesized that specifically cleave RNA-encoding chloramphenicol acetyl
      transferase sequences. Methods are presented for the transcription of Rzs of
      virtually any length and sequence composition at a fraction of the cost of
      chemical synthesis.

PMID- 7526873
TI  - Early lesion development in the aortas of rabbits fed low-fat, cholesterol-free,
      semipurified casein diet.
AB  - The initial endothelial morphological alterations and the development of raised,
      lipid-containing lesions in rabbit aortas were examined after 1 and 3 months on a
      casein-enriched, semipurified, cholesterol-free diet. The alterations were
      compared with those in rabbits fed soy-protein in the place of casein and with
      age-matched, chow-fed, control animals. Using immunohistochemistry macrophages, T
      lymphocytes, and smooth muscle cells were identified in the lesions, and an
      expression of leukocyte adhesion molecules, VCAM-1, ICAM-1 and, occasionally, E
      selectin was seen in sections of the aortas of casein-fed rabbits. The initial
      alterations in the endothelium appear to include evidence of endothelial injury
      and white blood cell adhesion. No evidence of extracellular liposome formation
      was observed. This model of atherogenesis is consistent with endothelial injury
      being an important component of diet-induced atherogenesis and has similarities
      to human atherosclerosis.

PMID- 7526878
TI  - Examination of compact bone microdamage using back-scattered electron microscopy.
AB  - A new staining technique using heavy metals (lead-uranyl acetate) has been
      developed to allow visualization of bone microdamage using both light microscopy
      and scanning electron microscopy operated in its back-scattered mode (BSE). At
      the light microscopic level, the number of microcracks counted in sequential
      sections of human ribs is the same for both the traditional basic fuchsin method
      of differentially staining microcracks and the new lead-uranyl acetate procedure.
      With BSE study, however, the number of microcracks observed is significantly
      reduced in all samples, because of the reduction of projection effect error
      associated with surface based imaging techniques. Application of the lead-uranyl
      acetate staining technique to ex vivo-loaded crack propagation specimens showed
      an extensive ultrastructurally disrupted region associated with the crack path
      through bone, consistent with the damage process zone around cracks in toughened
      composite materials.

PMID- 7526881
TI  - Temporal control of gene expression from endogenous and exogenously-introduced
      DNAs in early embryogenesis of Xenopus laevis.
AB  - We review here our studies on temporal control of the expression of genes in
      zygotic nucleus and of exogenously introduced genes in Xenopus embryos. For
      zygotic gene expression, our studies have revealed that mRNA synthesis, tRNA
      synthesis and rRNA synthesis initiates at the cleavage stage, MBT stage and late
      blastula stage, respectively. We also briefly summarize here results of the
      effects of weak bases on rDNA expression, nucleo-cytoplasmic transport and
      polysomal mobilization of newly-synthesized RNAs. For exogenously injected genes
      expression our data have shown the control of the expression by the promoter and
      configuration (circular or linear) of the injected DNAs but not necessarily by
      cellular changes that take place during the midblastula transition (MBT).

PMID- 7526880
TI  - Localization of mitochondrial large rRNA in germinal granules and the consequent
      segregation of germ line.
AB  - This article reviews recent studies on cytoplasmic factors for germ-line
      establishment in Drosophila and Xenopus. In a variety of animal groups, the
      cytoplasmic factors for germ-line differentiation have been postulated to be
      localized in the germ plasm. We have found that mitochondrial large rRNA
      (mtlrRNA) is present in germinal granules, the distinctive morphological markers
      of germ plasm in the fruit-fly and the frog. MtlrRNA has been identified as a
      cytoplasmic factor that induce pole cells, the progenitor of the germ line, in uv
      sterilized Drosophila embryos. The developmental stages of Xenopus at which
      mtlrRNA is present in germinal granules correspond to the stages of germ line
      segregation. Based on our findings and available data on posterior class gene
      products as well as on classical developmental biology of germ cells, we discuss
      the probable role of mtlrRNA in germ-line segregation from the somatic line in
      these animals.

PMID- 7526882
TI  - Regulation of pepsinogen gene expression in epithelial cells of vertebrate
      stomach during development.
AB  - Pepsinogens are zymogens of pepsins, aspartic proteases working as digestive
      enzymes in the vertebrate stomach, of which biological and molecular properties
      have been extensively studied. In developmental biology, pepsinogens offer
      excellent molecular markers of differentiation of stomach epithelial cells, since
      their expression is strictly limited to those cells and there are some isozymes
      that are expressed in developmental stage-specific manner. It is now well
      established that the expression of embryonic chicken pepsinogen (ECPg) gene is
      regulated by epithelial-mesenchymal interactions: it is mesenchyme that
      determines the expression pattern of ECPg along the digestive tract, by
      supporting or inhibiting the intrinsically endowed ability of epithelial cells to
      express it. In the present review article, I will describe recent molecular
      biological and experimental embryological consequences of our studies on the
      regulation of ECPg expression by mesenchymal cells, with special attention to the
      nature of mesenchymal factors and the molecular mechanisms of reactivity of
      epithelial cells to the mesenchymal influences.

PMID- 7526883
TI  - Tenascin expression and postnatal development of the human prostate.
AB  - We investigated the distribution of tenascin during postnatal development of the
      human prostate. Monoclonal antibody specific to human tenascin was applied to
      paraffin sections by the avidin-biotin-complex method to examine its
      localization. Infantile prostates showed two distinct zones. The inner zone had
      sparse acini with fibromuscular bundles. The peripheral zone had similar acini
      and lighter stroma as compared with inner zone. Tenascin was found diffusely but
      weakly. The periglandular area occasionally showed immunoreactivity. The
      prostates from 9- to 13-year-old subjects had a morphology similar to that of the
      infantile gland. The difference was increased density of the acini.
      Immunoreactivity was low. In the prostates from 14- to 21-year-old subjects, the
      acini distribution was more crowded, and the epithelial lining had become taller
      in both zones. Tenascin distributed preferentially in the peripheral zone during
      this period. Simultaneously, the percent of glandular area in the peripheral zone
      rose abruptly. The dynamics of tenascin expression are closely associated with
      the development and maturation of the gland. The distribution of tenascin during
      the post-puberal period may suggest its participation in the preferential of
      prostatic carcinoma in the peripheral zone.

PMID- 7526879
TI  - On the histologic measurement of osteonal BMU activation frequency.
AB  - When cortical bone is remodeled by osteonal basic multicellular units (BMUs),
      activation frequency is defined as the number of new BMUs created per unit volume
      of cortex per unit time. When osteonal remodeling is histomorphometrically
      analyzed, a different definition of activation frequency is usually used; it is
      equivalent to the number of previously activated BMUs reaching the plane of the
      section per unit area per unit time. Using simple geometric analysis, it is shown
      that the latter histologic measurement is equal to the former definition
      multiplied by the mean distance that a BMU tunnels before it ceases its activity.

PMID- 7526884
TI  - Oestrogen and epidermal growth factor down-regulate erbB-2 oncogene protein
      expression in breast cancer cells by different mechanisms.
AB  - Mitogen-induced mammary cell growth is often accompanied by decreased levels of
      expression of the p185erbB-2 protein. We have previously reported that oestrogen
      inhibits erbB-2 mRNA and protein expression in breast cancer cells, while
      epidermal growth factor (EGF) treatment has been shown to decrease p185erbB-2
      levels in normal mouse mammary epithelial cells. In the present work, we studied
      the effect of oestrogen and EGF on erbB-2 expression in oestrogen-responsive
      breast cancer cells. We observed that both oestrogen and EGF comparably down
      regulated p185erbB-2 levels, while stimulating growth of T47D and ZR75.1 cells.
      Oestrogens, but not EGF, concomitantly down-regulated erbB-2 mRNA. Run-on
      analysis showed a reduced erbB-2 transcription rate in the presence of
      oestrogens. Furthermore, the transcriptional activity of a 219 bp proximal
      fragment of the human erbB-2 promoter was repressed by oestrogens, whereas it was
      enhanced by EGF. EGF stimulated both tyrosine phosphorylation and autokinase
      activity of p185erbB-2 down-regulates p185erbB-2 at a post-translational level.
      Thus, two factors converging in terms of effects on cell growth, display
      divergent mechanisms of regulation of erbB-2 expression.

PMID- 7526885
TI  - DT-diaphorase protects cells from the hypoxic cytotoxicity of indoloquinone EO9.
AB  - Aerobic sensitivity to indoloquinone EO9 has been shown to correlate with
      cellular levels of the two-electron reducing enzyme DT-diaphorase. However,
      little is known about the relative roles of one- and two-electron reducing
      enzymes in the hypoxic cytotoxicity of EO9. We have characterised a panel of 23
      human tumour cell lines for both bioreductive enzyme activities and aerobic
      sensitivity to EO9. Eight cell lines were then selected for a comparison of
      aerobic and hypoxic sensitivities. Activities of DT-diaphorase showed a wide
      range (> 10,000-fold), while activities of the one-electron reducing cytochrome
      b5 and cytochrome P450 reductases were generally lower and showed only a 15- and
      25-fold range respectively. The aerobic cytotoxicity of EO9 was clearly related
      to the cellular levels of DT-diaphorase (r = 0.87), with higher levels giving
      increased sensitivity, but not to the levels of one-electron reducing enzymes. In
      contrast, there was no relationship between sensitivity to BCNU, cisplatin or the
      bioreductive agent SR 4233 (tirapazamine) and activities of any of these reducing
      enzymes. Under hypoxic conditions sensitivity to EO9 was markedly increased in
      cell lines with low levels of DT-diaphorase activity, while cell lines with high
      levels show only a small increase in sensitivity. This is reflected by a clear
      correlation (r = 0.98) between cellular DT-diaphorase activity and the ratio of
      aerobic to hypoxic sensitivity to EO9. However, we have now for the first time
      demonstrated an inverse correlation (r = 0.93) between the cellular activity of
      DT-diaphorase and hypoxic sensitivity to EO9, that is sensitivity decreases with
      increasing DT-diaphorase activity. Moreover, this correlation was lost when cells
      were exposed to drug in the presence of dicoumarol, supporting an involvement of
      DT-diaphorase in this relationship. These observations question the previously
      straightforward role for DT-diaphorase in the metabolic activation of EO9.
      Whereas DT-diaphorase is associated with increased toxicity in air, it appears to
      reduce the cytotoxicity of EO9 in hypoxic conditions. This suggests either that
      the one-electron reduction product of EO9 metabolism, the semiquinone, is more
      toxic than the two-electron reduction product, the hydroquinone, or that the
      hydroquinone is not cytotoxic and aerobic toxicity is due to the transient
      appearance of the semiquinone upon back oxidation of the hydroquinone.

PMID- 7526888
TI  - Inverse relationships between cell proliferation and basal or androgen-stimulated
      apolipoprotein D secretion in LNCaP human prostate cancer cells.
AB  - We have recently demonstrated that the biphasic action of androgens on LNCaP cell
      proliferation is opposite to their effect on apolipoprotein D (apo-D) secretion,
      the stimulation of apo-D secretion being associated with a steroid-induced
      inhibition of cell proliferation. To further characterize the control of apo-D
      expression in LNCaP cells, we studied basal as well as androgen-induced apo-D
      secretion in slowly proliferating, low-passage (LP; 20-29th) and rapidly
      proliferating high-passage (HP; 111-117th) cell cultures. For comparison, the
      androgen-induced stimulation of prostate specific antigen secretion was also
      investigated in LP and HP cell cultures. In the absence of androgens, basal cell
      proliferation of HP cells was significantly higher than that of LP cells, whereas
      apo-D secretion was higher in LP cells than in HP cells. Furthermore, the
      biphasic action of dihydrotestosterone and of the synthetic androgenic compound
      R1881 on apo-D release and cell proliferation was observed in both LP and HP
      cells. The stimulation of apo-D secretion was inversely related to that of cell
      proliferation and influenced by cell density. The inhibition of basal and
      androgen-induced cell proliferation by the calcium channel blocker nifedipine was
      also associated with an increase in apo-D secretion. The amount of PSA released
      and the sensitivity of its response to R1881 were increased in LP cells compared
      with HP cells. The present study thus demonstrates, for the first time, that apo
      D secretion is inversely correlated to cell proliferation and cell density in the
      absence as well as in the presence of androgens in both LP and HP LNCaP human
      prostate cancer cells. This finding suggests that apo-D expression can be
      modulated not only by steroid hormones, but also by other factors involved in the
      control of cell proliferation.

PMID- 7526886
TI  - Tumour angiogenesis in latent prostatic carcinoma.
AB  - Unrestrained growth of various malignant tumours has been shown to depend upon a
      critical number of tumour cells which have switched to the angiogenic phenotype.
      Angiogenic phenotypes were noted in the early stage of prostatic carcinoma (PCa).
      We investigated 65 cases of latent PCa to define the correlation between tumour
      angiogenesis and tumour volume. Tumour angiogenesis was determined by the blood
      capillary density ratio (BCDR) evaluated by a colour image analysis system. Using
      experimental regression analysis, the correlation between the BCDR and PCa volume
      was divisible into two distinct stages. When the PCa showed a volume of more than
      83 mm3, there was a significant positive correlation between the BCDR and PCa
      volume (rS-test P < 0.001). However, when the PCa showed a volume of less than 83
      mm3, the BCDR remained at a low level which did not change until larger volumes
      were present (rS-test, NS; ANOVA, NS). The present study suggested that latent
      PCa showing a volume of less than 83 mm3 would be 'early' indolent carcinoma
      which, on undergoing additional events concerning tumour angiogenesis, would
      assume more aggressive growth.

PMID- 7526887
TI  - Loss of the retinoblastoma susceptibility gene (RB1) is a frequent and early
      event in prostatic tumorigenesis.
AB  - Loss of the RB1 gene is an important event in the initiation and progression of
      many tumours. Prostate tissue from 43 patients with prostate cancers and ten with
      benign prostatic hypertrophy (BPH) were studied for loss of heterozygosity of the
      RB1 gene. Four intragenic polymorphic loci were studied with two techniques.
      These were restriction fragment length polymorphism (RFLP). Southern blotting and
      hybridisation with the p123m1.8 and p68RS2.0 probes (to introns 1 and 17
      respectively) and also the polymerase chain reaction (PCR) to amplify loci within
      introns 17 and 20. Protein product (pRB) expression was determined by
      immunohistochemistry using the NCL-RB antibody in nine patients with cancer and
      four patients with BPH. Loss of heterozygosity was found in 24 out of 40 (60%)
      informative patients with cancer. Loss of RB1 occurred with a similar frequency
      in early-stage and low-grade cancers as in more advanced cancers. Loss of RB1 was
      also found in one patient with BPH. Expression of pRB was completely absent from
      seven cancers and markedly reduced in the other two, while nuclear pRB staining
      was always present in areas of BPH, whether alongside cancer-containing tissue or
      with BPH alone. We conclude that loss of RB1 is an early event in prostatic
      tumorigenesis.

PMID- 7526890
TI  - Interleukin 10 inhibits T cell alloreaction induced by human dendritic cells.
AB  - Human dendritic cells (DC) generated from CD34+ hematopoietic progenitors
      cultured in the presence of granulocyte macrophage colony stimulating factor (GM
      CSF) and tumor necrosis factor (TNF)-alpha are related to Langerhans cells (DLC)
      and have been shown to induce a strong proliferation of allogeneic CD4+ T cells.
      The present study shows that recombinant human IL-10 (h-IL-10) inhibits the
      primary and secondary proliferative responses of both CD4+ and CD8+ T cells
      induced by allogeneic CD1a+ DLC. The alloreaction induced by DLC generated after
      5-18 days of culture of CD34+ HPC was equally inhibited by h-IL-10, thus
      indicating that DLC were sensitive to h-IL-10 at all stages of differentiation.
      This is further indicated by the h-IL-10-induced inhibition of the T cell
      alloreaction mediated by interdigitating DC freshly isolated from tonsils. h-IL
      10 specifically acted on DLC as it did not affect the proliferation induced by
      Epstein-Barr virus lymphoblastoid cell lines (EBV-LCL) nor that induced by
      immobilized anti-CD3. The inhibitory effect of h-IL-10 was not due to the
      production of suppressive factors by the DLC, as the addition of DLC and IL-10
      did not inhibit EBV-LCL-induced T cell proliferation. Rather, the inhibition of
      cytokine production (IL-2, GM-CSF, TNF, IFN-gamma) observed after 24 h of co
      culture may explain the inhibition of T cell DNA synthesis detected 3 days later.
      The h-IL-10-induced inhibition of human DC mediated alloreaction advocates
      considering the use of h-IL-10 in the prevention of transplant rejection and
      graft versus host disease, phenomena initiated by DC.

PMID- 7526889
TI  - IFN consensus sequence binding protein (ICSBP) is a conditional repressor of IFN
      inducible promoters.
AB  - IFN stimulated genes (ISGs) contain common DNA motif termed IFN consensus
      sequence (ICS) at their promoters that enable IFN responsiveness. Different
      transcription factors capable of interacting with the ICS have been described.
      Previously, we reported the cloning of a factor capable of binding to the ICS
      (ICSBP) that demonstrates similarity at DNA the binding domain with three other
      ICS binding factor, i.e. IRF-1, IRF-2 and ISGF3 gamma. ICSBP is expressed
      constitutively in hematopoietic cells and its expression is further induced by
      IFN-gamma. This is a negative trans-acting regulator of ISGs; however, its effect
      is attenuated following prolonged exposures of cells to both types of IFNs. In
      this communication, we show that short exposures of cells to IFNs (priming) are
      sufficient to alleviate ICSBP mediated repression. Further, exposure of primed
      cells to the synthetic dsRNA (polyl-polyC) results in total abrogation of ICSBP
      repression. In an attempt to unravel the molecular mechanism governing this
      conditional repression of ICSBP, the direct involvement of transcriptional
      activator IRF-1 is demonstrated. We postulate that constitutive expression of
      ICSBP in hematopoietic cells is mediating submaximal expression of ISGs such as
      MHC class I. Our data demonstrate that IRF-1 competes with ICSBP for the binding
      to the ISRE element, resulting in the alleviation of ICSBP repression. Thus, the
      magnitude of ISGs expression is a result of a fine balance between positive and
      negative regulators.

PMID- 7526892
TI  - A calcium- or manganese-dependent epitope on the integrin beta 1 chain recognized
      by a unique mAb.
AB  - A calcium- or manganese-dependent epitope was demonstrated on the beta 1 integrin
      chain by a newly established mAb. In immunoprecipitation, the mAb was able to
      bind to the solubilized beta 1 integrin chain in the presence of calcium but not
      magnesium. Cation chelating reagents completely affected the binding of the
      antibody to the intact beta 1 integrin chain on a cell surface. Calcium but not
      magnesium restored the binding of the antibody. Quantitative analyses revealed
      that chelating reagents reduced the affinity of the antibody. Moreover, manganese
      also rescued epitope expression. These results suggested that divalent cations,
      particularly calcium or manganese, had a crucial role in the conformation of the
      beta 1 integrin chain recognized by the SG/7 antibody. This antibody would be of
      great use for studying the divalent cation-dependent modulation of the integrin
      molecules and bring another aspect to the understanding of the regulatory
      mechanisms of ligand binding of the integrin molecules.

PMID- 7526893
TI  - Mel14+ CD4+ T cells from aged mice display functional and phenotypic
      characteristics of memory cells.
AB  - Aging is accompanied by an increased fraction of memory CD4+ T cells. Despite the
      fact that human memory cells have been reported to produce high levels of IL-2,
      studies in mice and man indicate an age-related decline in IL-2 production. In
      the present study, we examined whether these conflicting results depend on the
      activation pathway employed in a comparison of phenotypically distinct CD4+ T
      cells from young and aged mice. Our data indicate an age-related decline in IL-2
      production by CD4+ T cells when the cells were stimulated with concanavalin A in
      the presence of accessory cells or the combination of immobilized anti-CD3 and
      soluble anti-CD28. However, when CD4+ T cells were only stimulated with
      immobilized anti-CD3, an age-related increase in IL-2 production was observed.
      This age-related increase in IL-2 could be attributed to the ability of CD4+ T
      cells from aged mice to produce IL-4 on this stimulation, since anti-IL-4
      inhibited the IL-2 production in these cultures to levels found with cells from
      young mice. The addition of exogenous IL-4 greatly enhanced the IL-2 production
      of CD4+ T cells from young mice to levels far beyond that of the aged
      counterparts, emphasizing the dominant role of IL-4 in the induction of IL-2
      stimulated with immobilized anti-CD3. No differences were observed in the
      activation requirements of Mel14- CD4+ T cells from young and aged mice.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7526894
TI  - IL-2 receptor alpha chain (CD25, TAC) expression defines a crucial stage in pre-B
      cell development.
AB  - The analysis of the expression of the alpha chain of the IL-2 receptor (CD25,
      TAC) on the surface of B lineage cells in mouse bone marrow reveals that it is a
      useful marker to distinguish pre-B-I from pre-B-II cells. CD25 is not expressed
      on CD45R(B220)+ c-kit+ CD43+ TdT+ lambda 5+ c mu- sIg-IgH chain locus DJH
      rearranged pre-B-I cells of mouse bone marrow. It is expressed on large cycling
      CD45R(B220)+ c-kit- CD43+ TdT- lambda 5+ c mu+ sIg- and on small resting
      CD45R(B220)+ c-kit- CD43- TdT- lambda 5- c mu- sIg- IgH chain locus VHDJH
      rearranged pre-B-II cells. Therefore, the transition from pre-B-I to large pre-B
      II cells is marked by the downregulation of c-kit and terminal deoxynucleotidyl
      transferase (TdT), and by the upregulation of CD25. SCID, RAG-2T, microMT and
      lambda 5T mutant mice do have normal, if not elevated numbers of pre-B-I cells
      but lack all CD25+ pre-B-II cells in their bone marrow. The expression of a
      transgenic H chain under control of the microH chain enhancer in RAG-2T bone
      marrow B lineage precursors allows the development of large and small CD25+ pre-B
      II cells. The results suggest that the differentiation of pre-B-I to pre-B-II
      cells in mouse bone marrow requires the expression of microH chains and surrogate
      L chains in membranes, probably on the surface of precursor B cells.

PMID- 7526891
TI  - Influence of amino acids of a carrier protein flanking an inserted T cell
      determinant on T cell stimulation.
AB  - CD4+ helper T cells recognize antigen in association with MHC class II molecules.
      To investigate the role of the context of a minimal T cell epitope on
      presentation and recognition in association with MHC class II molecules, an
      epitope of the 65 kDa heat shock protein of Mycobacterium tuberculosis was
      inserted at four different sites in the outer membrane protein PhoE of
      Escherichia coli. Only some of the constructs could stimulate the epitope
      specific T cell clone A2b in vitro. One non-stimulatory construct could be made
      stimulatory by denaturation, suggesting that the protein conformation prevents
      correct presentation of the epitope. Other non-stimulatory constructs did not
      become stimulatory with denaturation. One of these constructs could be made
      stimulatory by substitution of either one of the two amino acids directly
      preceding the minimal epitope in the recombinant protein. In synthetic peptides
      the presence of these upstream residues did not interfere with T cell
      recognition, suggesting that these residues influence processing of the
      recombinant protein. Flanking amino acids also influenced induction of a T cell
      response against the inserted epitope in vivo. These results demonstrate that
      insertion of minimal T cell epitopes in carrier proteins for the design of
      vaccines might fail because of the inhibiting effects of flanking residues.

PMID- 7526895
TI  - The non-enzymatic specific amino-acylation of transfer RNA at high pressure.
AB  - This paper shows that the phenylalanine-specific tRNA of Escherichia coli as well
      as the yellow lupin methionine initiator tRNAMet can be charged specifically with
      phenylalanine and methionine, respectively, in the absence of specific aminoacyl
      tRNA synthetases, under high pressure of a maximum of 6 kbar (1 bar = 10(5) Pa; 1
      atm = 1.01 x 10(5) Pa). The esterification reaction takes places at the 3' end of
      the tRNA molecules. The yield of Phe-tRNAPhe or Met-tRNAMet at high pressure is
      approximately 10 times lower than that of the enzymatic aminoacylation reaction.
      This reaction seems to be specific, and mis-aminoacylation of tRNAPhe and tRNAMet
      with serine is negligible. It is well known that tRNA undergoes conformational
      changes during interaction with an aminoacyl-tRNA synthetase. Similarly, on the
      basis of circular dichroism spectra, we showed that the conformation of tRNA at
      high pressure differs slightly from its original A-RNA form. Therefore, it can be
      speculated that the chargeable conformation of tRNA induced by the aminoacyl-tRNA
      synthetase during enzymatic aminoacylation and the one created at high pressure
      are similar and are most probably formed by a dehydration mechanism. We think
      that the 'unique' tertiary structure of tRNA existing under high pressure creates
      an active centre which might itself catalyse ester bond formation. Therefore, the
      structure of the amino acid stem of tRNA may determine (code) the charging of the
      particular amino acid to specific tRNA. This code is clearly distinct from the
      rules of the classical genetic code.

PMID- 7526897
TI  - Study of the CN1 peptide of P2 protein using Fourier transform infra-red
      spectroscopy.
AB  - The conformation of the CN1 peptide, derived from the nervous system P2 protein,
      has been studied in deuterium oxide solution using Fourier transform infra-red
      (FTIR) spectroscopy. The peptide was found to be mainly random, with some alpha
      helix and beta-structure present. The open structure of CN1 indicates that the
      constraints necessary for formation of the largely beta-structure in P2 are
      removed by cleavage of the protein to form peptides. The study produced different
      quantitative estimations of secondary structures to those previously reported in
      circular dichroism studies, but the FTIR results are shown to be more reliable.

PMID- 7526896
TI  - A-Z-RNA conformational changes effected by high pressure.
AB  - This paper reports evidence obtained by circular dichroism (CD) spectroscopy
      measurements indicating that two oligoribonucleotide duplexes with the
      alternating purine-pyrimidine sequences r(GC)6 or r(AU)6 change their A-RNA
      conformation under high pressure. Under the high-pressure conditions at which B-Z
      DNA transition easily occurs, RNA acquires a conformation which only differs
      slightly from that of A-RNA. However, exposure of r(GC)6 or r(AU)6 to high
      pressure (6 kbar) in the presence of 5 M NaCl causes a conformation change of
      both oligoribonucleotide duplexes from their A- to their Z-RNA form. The
      departure of RNA or DNA duplexes from their original conformations under high
      pressure depends on the water structure itself and involves displacing an active
      (structural) water molecule outside the nucleic acid molecules. Experiments
      carried out until now in many laboratories have shown that B-Z or A-Z transitions
      of DNA or RNA, respectively, do not depend on the conditions applied, but the
      common mechanism for these processes seems to be dehydration. This same effect
      can be observed either at high salt concentrations or in the presence of an
      alcohol or at high pressure. Our results also support the view that the higher
      stability of RNA compared with DNA duplexes is due to the strong interaction of
      the 2'-hydroxyl groups of RNA with water molecules.

PMID- 7526898
TI  - Presence of LDL receptor-related protein/alpha 2-macroglobulin receptors in
      macrophages of atherosclerotic lesions from cholesterol-fed New Zealand and
      heterozygous Watanabe heritable hyperlipidemic rabbits.
AB  - Atherosclerotic lesions are composed of a complex mixture of cell types that are
      engorged with lipid and enveloped in extracellular matrix elements. This
      manifestation probably results from imbalances in the cellular processing of
      cholesterol-delivering lipoproteins, changes in extracellular matrix deposition,
      and growth factor elaboration. One receptor class that could modulate these
      processes is LDL receptor-related protein/alpha 2-macroglobulin receptors
      (LRP/alpha 2-MR). Consequently, the presence of LRP/alpha 2-MR was determined on
      a temporal basis in lesions of distinct morphologies that were developed in
      cholesterol-fed New Zealand and heterozygous Watanabe heritable hyperlipidemic
      (WHHL) rabbits. The two strains of rabbits developed similar degrees of
      hypercholesterolemia in response to 0.5% wt/wt cholesterol in their diet.
      Lipoprotein-cholesterol distribution was also similar in the two strains. Aortic
      intimal areas covered by grossly discernible atherosclerotic lesions were
      extensive and not statistically different between the strains. Despite the
      similarities in the extent of hypercholesterolemia, lipoprotein distribution, and
      extent of atherosclerosis, the cellularity of the lesions formed was different in
      the two groups. Atherosclerotic lesions in cholesterol-fed New Zealand rabbits
      were uniformly rich in macrophages and deficient in smooth muscle cells, as
      determined by immunocytochemical staining with the cell-specific monoclonal
      antibodies RAM-11 and HHF-35. In contrast, atherosclerotic lesions formed in
      cholesterol-fed heterozygous WHHL rabbits covered a spectrum ranging from
      macrophage-rich lesions to those predominantly composed of disaggregated smooth
      muscle cells that were embedded in dense layers of extracellular matrix.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7526899
TI  - Lactoferrin binding to heparan sulfate proteoglycans and the LDL receptor-related
      protein. Further evidence supporting the importance of direct binding of remnant
      lipoproteins to HSPG.
AB  - Bovine lactoferrin inhibits the clearance of remnant lipoproteins from the plasma
      and competes with the cell-surface binding of apolipoprotein (apo) E-enriched
      remnants. We established that lactoferrin inhibits remnant binding and uptake by
      interacting with both heparan sulfate proteoglycans (HSPG) and the low-density
      lipoprotein receptor-related protein (LRP). The binding of 125I-lactoferrin was
      inhibited 45% to 60% in HepG2 hepatocytes and wild-type Chinese hamster ovary
      (CHO) cells treated with heparinase to remove HSPG. In mutant CHO cells (pgsD
      677) lacking HSPG, the level of 125I-lactoferrin binding was approximately 50%
      that seen with wild-type CHO cells; thus, about one half of lactoferrin binding
      appears to be mediated through cell-surface HSPG. A significant fraction of the
      residual binding of the lactoferrin appears to be mediated through the LRP. The
      39-kd protein known to bind to the LRP and to block ligand interaction inhibited
      125I-lactoferrin degradation in wild-type CHO cells by 60% to 65%. The addition
      of the 39-kd protein plus heparinase treatment reduced the binding by 85% to 90%
      (this combination blocks direct interaction with both the LRP and HSPG). However,
      it was also shown that the 39-kd protein bound to HSPG and the LRP. Heparinase
      treatment of wild-type CHO cells decreased the binding of the 125I-39-kd protein
      by approximately 40%, and the mutant CHO cells lacking HSPG bound half as much
      125I-39-kd protein as wild-type CHO cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526901
TI  - Acute responses of non-human primates to airway delivery of an adenovirus vector
      containing the human cystic fibrosis transmembrane conductance regulator cDNA.
AB  - Recombinant human adenovirus (Ad) vectors are leading candidates for human gene
      therapy for cystic fibrosis (CF) based on demonstration of efficient transfer of
      exogenous genes to rodent respiratory epithelium in vivo and human respiratory
      cells in vitro. The safety of Ad-mediated gene transfer to the respiratory
      epithelium and acute (up to 21 days) clinical responses to airway delivery of a
      replication-deficient recombinant, E1-, E3- Ad type 5-based vector containing the
      human cystic fibrosis transmembrane conductance regulator cDNA (AdCFTR) were
      evaluated in rhesus monkeys. Airway delivery of an Ad vector with the lacZ marker
      gene demonstrated beta-galactosidase expression in epithelial cells. Animals
      administered intratracheal AdCFTR demonstrated human CFTR cDNA expression in
      airway epithelial cells. Animals administered AdCFTR intranasal, and 24 hr later,
      intrabronchial [2 x 10(7) to 5 x 10(10) plaque-forming units (pfu), n = 12], in a
      fashion similar to a proposed human protocol, or only intrabronchial (10(11) pfu,
      n = 3), had no significant changes in clinical parameters compared to vehicle
      controls (n = 6). Microscopic analysis of the lung by necropsy or bronchoalveolar
      lavage demonstrated a dose-dependent increase in inflammatory cells, primarily
      lymphocytes, in the area where AdCFTR was delivered, which persisted for at least
      2 months in some animals. Serum anti-Ad type 5 neutralizing antibody titers did
      not rise and shed Ad was not detected. The presence of AdCFTR DNA, analyzed by
      the polymerase chain reaction (PCR), was not detected in organs outside the lung.
      These data demonstrate that AdCFTR is well tolerated in non-human primates,
      although there is dose-dependent inflammation in the lung not clinically
      apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526900
TI  - Identification of residues in the monoclonal antitumor antibody L6 important for
      binding to its tumor antigen.
AB  - L6 is a monoclonal antitumor antibody which recognizes an epitope located in a 42
      residue extracellular domain of a tumor-associated approximately 22 kDa
      glycoprotein antigen. The L6 mAb localizes to solid tumors in vivo and triggers
      complement activation and antibody-dependent cellular cytotoxicity. It has been
      the subject of phase I clinical trials. Previously, we had reported the
      derivation and analysis of a three-dimensional model of the L6 Fv. The model
      suggests that L6 displays a generally aromatic CDR surface. We aim at improving
      the affinity for tumor antigen of L6 by in vitro mutagenesis. As the first step
      toward this end, we have attempted to identify residues critical for the binding
      of L6 to tumor antigen. On the basis of the model, seven residues were selected
      which we thought may be critical for L6 antigen binding. Criteria for the
      selection of these residues were their accessibility and central position on the
      CDR surface and the residue character. Large polar or charged residues such as
      arginine, asparagine, and tyrosine were preferred. Nine site-specific single and
      double mutants were generated using oligonucleotide-directed mutagenesis in an
      M13 expression vector encoding the L6 Fab. The binding of these mutant Fabs to
      the L6 tumor antigen and a set of three anti-idiotypic antibodies was quantified
      in an ELISA. In eight out of nine mutants, binding to L6 tumor antigen was either
      abolished or substantially reduced. In contrast, the binding of the mutants to
      the anti-idiotypic antibodies was largely unaffected, suggesting that no
      significant structural perturbations were introduced as a consequence of these
      mutations.

PMID- 7526902
TI  - Retroviral mediated transfer of the human multidrug resistance gene (MDR-1) into
      hematopoietic stem cells during autologous transplantation after intensive
      chemotherapy for metastatic breast cancer.
AB  - Patients with metastatic breast cancer will receive 4-5 cycles of induction
      chemotherapy on one of the ongoing Medicine Branch protocols. Patients achieving
      at least a partial response, and who do not have evidence of bone marrow
      involvement and who do not have metastatic bone disease, will undergo PBSC and
      bone marrow harvest when hematologic recovery has occurred. Patients who have not
      achieved a PR, but who are responding to therapy, may be treated with additional
      cycles of therapy in an attempt to achieve a PR. Such patients will be eligible
      for transplant if a PR is obtained. 70% of the bone marrow and PBSC will be
      cryopreserved. The CD34+ subpopulation from the remaining 30% of the bone marrow
      and PBSC harvest will be obtained using an anti-CD34+ antibody and
      immunoabsorption column. The bone marrow and peripheral blood CD34 cells will be
      transduced with a retroviral vector expressing the human MDR-1 cDNA. Patients
      with positive bone scans or histologic evidence of bone marrow involvement will
      be excluded from the gene transfer component of the protocol. The MDR-1
      transduced CD34 cells will be reinfused along with the non-transduced bone marrow
      and PBSC into patients following high dose ICE chemotherapy. Serial peripheral
      blood and bone marrow samples will be obtained to study hematopoietic
      reconstitution with MDR-1 transduced cells. Patients with residual or progressive
      disease after ABMT will be treated with taxol or vinblastine. In these relapsed
      patients, peripheral blood and bone marrow samples will be obtained to study
      whether chemotherapy amplifies the proportion of hematopoietic cells containing
      the MDR-1 provirus. We will monitor the nadir blood counts of each patient
      receiving salvage chemotherapy for evidence of myeloprotection and correlate this
      data with changes in the mean proviral copy number. Sites of relapsed tumor will
      be biopsied to test for the presence of the MDR-1 provirus.

PMID- 7526903
TI  - Separation of 32P-postlabeled DNA adducts of polycyclic aromatic hydrocarbons and
      nitrated polycyclic aromatic hydrocarbons by HPLC.
AB  - The 32P-postlabeling assay, thin-layer chromatography, and reverse-phase high
      pressure liquid chromatography (HPLC) were used to separate DNA adducts formed
      from 10 polycyclic aromatic hydrocarbons (PAHs) and 6 nitrated polycyclic
      aromatic hydrocarbons (NO2-PAHs). The PAHs included benzo[j]fluoranthene,
      benzo[k]fluoranthene, indeno[1,2,3-cd]pyrene, benzo[a]pyrene, chrysene, 6
      methylchrysene, 5-methylchrysene, and benz[a]anthracene. The NO2-PAHs included 1
      nitropyrene, 2-nitrofluoranthene, 3-nitrofluoranthene, 1,6-dinitropyrene, 1,3
      dinitropyrene, and 1,8-dinitropyrene. Separation of seven of the major PAH-DNA
      adducts was achieved by an initial PAH HPLC gradient system. The major NO2-PAH
      DNA adducts were not all separated from each other using the initial PAH HPLC
      gradient but were clearly separated from the PAH-DNA adducts. A second NO2-PAH
      HPLC gradient system was developed to separate NO2-PAH-DNA adducts following one
      dimensional TLC and HPLC analysis. HPLC profiles of NO2-PAH-DNA adducts were
      compared using both adduct enhancement versions of the 32P-postlabeling assay to
      evaluate the use of this technique on HPLC to screen for the presence of NO2-PAH
      DNA adducts. To demonstrate the application of these separation methods to a
      complex mixture of DNA adducts, the chromatographic mobilities of the 32P
      postlabeled DNA adduct standards (PAHs and NO2-PAHs) were compared with those
      produced by a complex mixture of polycyclic organic matter (POM) extracted from
      diesel emission particles. The diesel-derived adducts did not elute with the
      identical retention time of any of the PAH or NO2-PAH standards used in this
      study. HPLC analyses of the NO2-PAH-derived adducts (butanol extracted) revealed
      the presence of multiple DNA adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526904
TI  - Chemoprevention of mammary tumor virus-induced and chemical carcinogen-induced
      rodent mammary tumors by natural plant products.
AB  - The natural plant products turmeric, beta-carotene, catechin, and betel leaf
      extract were evaluated for their antitumor effects on mammary tumorigenesis in
      murine mammary tumor expressing C3H (Jax) mice and in Wistar rats treated with
      the chemical carcinogen 7-12-dimethylbenz(a)anthracene (DMBA). Administration of
      turmeric through the diet and of beta-carotene, catechin, and betel leaf extract
      through the drinking water to virgin female C3H mice resulted in decreased tumor
      incidence and tumor burden. Administering 5% turmeric in the diet from 2 months
      of age showed suppression of mammary tumor virus-related reverse transcriptase
      activity and of preneoplastic changes in the mammary glands. Furthermore, feeding
      turmeric from 6 months of age resulted in a 100% inhibition of mammary tumors. In
      the DMBA model of rat mammary tumorigenesis, administration of turmeric,
      catechin, and betel leaf extract resulted in decreased tumor burden and tumor
      incidence, and a delay in the onset of mammary tumors.

PMID- 7526907
TI  - A comparative study on the effects of 5-fluorouracil on glycosaminoglycan
      synthesis during palate development in quail and hamster.
AB  - A comparative study was undertaken to investigate the effects of 5-fluorouracil
      (FU) on glycosaminoglycans (GAG) synthesis during morphogenesis of the secondary
      palate in birds (where, unlike mammals, palate morphogenesis begins in a
      horizontal direction ad initium and lacks mammalian-type shelf reorientation) and
      mammal. Previous studies have shown that FU induces cleft palate in both birds
      and mammals. Air sacs of quail eggs were injected with 100 micrograms FU in 0.1
      ml saline or 0.1 ml saline only. Hamsters were given intramuscular injection of
      81 mg/kg FU in 1 ml saline or 1 ml saline only. Total GAG synthesis was measured
      by incorporation of 3H-glucosamine. Sulfated and non-sulfated GAGs were
      identified by Alcian Blue histochemistry combined with the use of GAG-degrading
      enzymes. The results indicated that a continuous synthesis of GAG at a steady
      rate was associated with normal palate morphogenesis in both quail and hamster.
      The amount of GAG synthesized in hamster palate was four-fold higher than in
      quail palate. In contrast to the developing hamster palate where the predominant
      GAG was hyaluronate, the major GAGs present during quail palate development were
      sulfated and were concentrated on the nasal side. FU treatment did not affect the
      rate of GAG synthesis in the developing palate of quail. In contrast, FU
      administration altered the rates of GAG synthesis, and affected hyaluronate
      accumulation, during palate morphogenesis in hamster.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7526908
TI  - Polarization microscopy of picrosirius red stained sections: a useful method for
      qualitative evaluation of intestinal wall collagen.
AB  - Collagen pattern in healing anastomosis of intestinal wall was compared with its
      normal pattern in the submucosal layer. Polarization colours were recorded for
      thin (0.8 micron or less) and thick (1.6-2.4 micron) collagen fibres. The
      polarization colours of thick collagen fibres in the anastomotic site were more
      greenish-yellow and yellow than those in normal intestine which were more
      yellowish-orange and orange. These findings indicate that the collagen in the
      anastomotic site 4 days after operation is less packed than the collagen of
      normal rat intestine. Examination of the polarization colours of Picrosirius red
      stained sections is a useful procedure to follow healing of anastomotic sites or
      diagnosis of collagen pathology in different pathologic conditions in the
      intestinal wall.

PMID- 7526906
TI  - The use of fluorescent dextrans as a marker of sarcolemmal injury.
AB  - We investigated the use of intravenously injected fluorescent dextran molecules
      (FDx) as a histological marker of sarcolemmal injury. Using fluorescent
      microscopy, uptake of FDx (average MW 10 kD) was assessed in sections of
      quadriceps muscles from three models: 1) normal (C57BL/10SnJ) mice, 2) normal
      mice run downhill (0, 3, and 7 days post exercise), and 3) non-exercised mdx
      (dystrophin-deficient) mice. These were compared to serial sections stained with
      hematoxylin and eosin (H&E). In control muscles, strong fluorescence was seen
      between fibers (intercellular). Intracellular FDx was observed within cells of
      the quadriceps from normal mice run downhill at days 0 and 3 post exercise, but
      not at day 7. On H&E staining, muscle pathology was not observed until day 3,
      with regeneration by day 7. Intracellular FDx was also observed within mdx
      muscles, particularly in fibers that appeared pre-necrotic on H&E stained
      sections. FDx appears to be useful as a histological marker of changes in
      sarcolemmal integrity associated with muscle injury from eccentric exercise or
      muscle disease.

PMID- 7526905
TI  - Regulation of insulin-like growth factors by antiestrogen.
AB  - Insulin-like growth factors are potent mitogens for breast cancer cell
      proliferation. This effect is modulated by the circulatory and extracellular
      IGFBPs as well as by the affinity of ligand binding receptors on the target
      cells. Antiestrogens have been shown to reduce both circulatory and
      microenvironmental IGF levels and thus suppress the IGF-I-induced growth of both
      ER-positive and ER-negative breast cancer cells. However, the effects of
      antiestrogens in down regulation of type I IGF receptor and in altering the
      autophosphorylation tyrosine kinase activity of EGF receptors are mainly observed
      in ER-positive cells. Furthermore, alteration of IGFBP by antiestrogens such as a
      marked increase of IGFBP-I production have been shown to inhibit the
      proliferative effect of IGF-I on ER-positive, but stimulate this effect, on ER
      negative cells. Such differential effects from IGF receptor and IGFBP may explain
      the clinical outcome that tumor regression from antiestrogens is mainly observed
      in ER-positive type. This assumption based on IGF regulation alone is certainly
      an oversimplistic view amid the complexity of autocrine, paracrine, and endocrine
      functions.

PMID- 7526909
TI  - Lectin histochemistry of human meningiomas.
AB  - The lectins Peanut agglutinin (PNA), Canavalia ensiformis (Con A), Ulex europaeus
      1 (UEA-1), Dolichos biflorus (DBA), Triticum vulgaris (WGA) were studied in a
      series of 36 meningiomas (16 meningotheliomatous-including 3 recurrences, 7
      transitional, 4 angiomatous, 2 "hemangiopericytic", 3 papillary-including 1
      recurrence, 4 anaplastic-including 3 recurrences. PNA binds to all cases of
      meningotheliomatous, transitional, papillary and anaplastic meningiomas
      (including recurrent cases) but the staining is more intense in tumor cells of
      anaplastic and papillary type. A semiquantitative study showed differences of PNA
      reactivity in the different subtypes of meningiomas. In meningotheliomatous
      meningiomas PNA-positivity was encountered in numerous neoplastic cells (50%),
      whereas papillary and anaplastic subtypes expressed strong cytoplasmic staining
      of few tumor cells (< 5%). Con A shows the same pattern of reactivity described
      for PNA, but more weakly. Our results suggest that PNA is a marker of
      differentiation in meningiomas rather than malignant transformation and can have
      prognostic relevance.

PMID- 7526910
TI  - Hormonal receptors, cell proliferation fraction (Ki-67) and c-erbB-2
      amplification in breast cancer. Relationship between differentiation degree and
      axillary lymph node metastases.
AB  - In view of the limitations of conventional prognostic factors such as
      differentiation degree, metastatic lymph nodes, hormonal receptors and others,
      especially when early lesions are found, additional new markers have been
      studied, such as gene amplification and cell proliferation index, in order to
      choose the appropriate treatment. Primary breast carcinoma tumors from 97
      patients were examined for differentiation degree, metastatic lymph nodes,
      hormonal receptors, c-erbB-2 amplification and cell proliferation index (Ki-67).
      A negative relationship with hormonal receptors and c-erbB-2 amplification, Ki-67
      and differentiation degree was found, whereas the relationship between c-erbB-2,
      Ki-67 and differentiation degree was positive. No relationship was found between
      these factors and metastatic lymph nodes. The concurrence of high cell
      proliferation index, c-erbB-2 amplification and negative hormonal receptor
      presence would indicate a subpopulation with a high risk of recurrence. But a
      larger survival study is necessary to correlate these factors with clinical
      outcome.

PMID- 7526912
TI  - Effects of spatial distribution on proton relaxation enhancement by particulate
      iron oxide.
AB  - The proton relaxation effect of superparamagnetic iron oxide (SPIO) particles
      under varying conditions of spatial distribution was investigated with use of
      phantoms. Agar phantoms containing various concentrations of SPIO or
      gadopentetate dimeglumine, with and without Sephadex beads, were studied.
      Phantoms with Sephadex had a heterogeneous spatial distribution of iron oxide,
      comparable to liver tissue in vivo. Relaxometry at 0.47 T showed decreased T2
      relaxivity of SPIO in Sephadex phantoms compared with that in agar phantoms
      without Sephadex. On T2-weighted images obtained at 1.5 T, the signal intensity
      of Sephadex phantoms showed less SPIO relaxation effect than that of plain agar
      phantoms. Unlike SPIO, gadopentetate dimeglumine showed the same relaxivities and
      signal intensity in plain agar and Sephadex phantoms. The results show that the
      T2 relaxation effect of iron oxide depends on its spatial distribution. A
      heterogeneous spatial distribution, as in intact liver tissue, diminishes the T2
      relaxivity of iron oxide particles.

PMID- 7526911
TI  - High endothelial venules and cell adhesion molecules in B-cell chronic
      lymphocytic leukaemia and related low grade B-cell lymphoma/leukaemia: II.
      Expression of cell adhesion molecules in lymph nodes biopsies.
AB  - The expression of cell adhesion molecules (LECAM-1, LFA-1, VLA-4, ICAM-1 and
      CD44) of lymph nodes from B-cell chronic lymphocytic leukaemia (B-CLL; mature: 16
      cases, immature: 8), lymphocytic lymphoma (LL; M:5, IM:2) and reactive lymph
      nodes (10) were investigated in frozen tissue sections. In order to assess the B-
      and T-cell compartments of the lymph nodes some additional markers CD3, CD20,
      CD45 RO were used, and for follicular dendritic reticulum cells (FDCs) CD35. The
      expression of the LECAM-1 molecule was correlated to the expression of activation
      (CD23, CD25) and proliferation (Ki67) markers. Findings, in accordance with the
      relevant data of the literature, indicate that B-CLL and LL show and identical
      adhesion profile to the mantle zone of the germinal centres of reactive lymph
      nodes; namely, they were CD44+/LECAM-1+/VLA-4+. The T-zones of the reactive lymph
      nodes were characterized by an LFA-1+ and the follicles by an ICAM-1+ pattern,
      while in B-CLL and LL cases the LFA-1+ and ICAM-1+ were detected without
      coexpression of these molecules in only a small number of cases. The ratio and
      location of CD3+ and LFA-1+ cells was very similar in lymph nodes from B-CLL and
      LL, and from this fact may arise the suspicion that LFA-1+ reported in LL cases
      derive from the sometimes significant T-cell compartment of the diseased lymph
      nodes. The LECAM-1 molecule did not show any correlation with the investigated
      activation/proliferation markers.

PMID- 7526915
TI  - Crystal structure of the phosphotyrosine recognition domain SH2 of the Src
      oncogene product complexed with tyrosine-phosphorylated peptides.
AB  - SH2 domains are protein modules specialized in recognizing phosphorylated
      tyrosine residues and their sequence contexts. The mechanism of phosphotyrosine
      recognition and context recognition was elucidated in a series of X-ray
      crystallographic experiments which are discussed below.

PMID- 7526913
TI  - [The testing of the carcinogenic potential of different chemical substances and
      radiations].

PMID- 7526914
TI  - Monitoring canine lung allograft rejection using Ia antigen expression by
      bronchoalveolar lymphocytes.
AB  - The expression of Ia antigens by lymphocytes in bronchoalveolar lavage (BAL) was
      evaluated after canine lung allotransplantation with immunosuppression using FK
      506. The expression of Ia antigens labeled using an OKIa-1 monoclonal antibody
      from Ortho Diagnostic Systems was measured by flow cytometry. Twenty-three adult
      mongrel dogs underwent left lung allotransplantation and were treated with FK-506
      at a dose of 0.1 mg/kg/day intramuscularly until death. Allograft rejection was
      evaluated microscopically. The percentage of OKIa-1-positive cells among the BAL
      lymphocytes was 34.8% +/- 8.9% (mean +/- SD) from the allografted lungs showing
      no rejection, whereas it was 68.8% +/- 16.2% from the allografted lungs which
      showed rejection (P < 0.01). When a diagnosis of rejection was made prior to
      pathologic examination by an OKIa-1-positive lymphocyte percentage of 42% or
      more, the sensitivity, specificity, and accuracy of diagnosis were 100%, 87.5%,
      and 94.1%, respectively. Subsequently, pulse steroid therapy was attempted in
      those dogs with a high rate of OKIa-1-positive lymphocytes in the BAL. In 3 of 4
      dogs showing histological signs of rejection, a decrease in the rate of OKIa-1
      positive cells among the BAL lymphocytes corresponded to an improvement in
      pathologic diagnosis. In two dogs with bacterial pneumonia and pulmonary vein
      thrombosis, densities indistinguishable from those of rejection were seen on
      chest roentgenograms, but in these dogs the rate of OKIa-1-positive BAL
      lymphocytes was 42% or less. In conclusion, Ia antigen expression by BAL
      lymphocytes could be useful for monitoring rejection in lung allotransplantation.

PMID- 7526918
TI  - Growth factor-regulated phosphatidylinositol-3-kinase in astrocytes. Involvement
      of pp60c-src.
AB  - Growth factors differently regulate astroglial cell differentiation and
      proliferation. In an effort to understand the early intracellular events promoted
      by growth factors in astroglial cells, we have determined the effects of IGF1,
      insulin, PDGF, EGF and FGFs on phosphatidylinositol-3 kinase. IGF1, PDGF and EGF
      which stimulate cell proliferation of astroglial cells, increased
      phosphatidylinositol-3 kinase activity immunoprecipitated with anti
      phosphotyrosine antibodies as shown by thin layer chromatography and high
      performance liquid chromatography. FGFa and FGFb, which strongly stimulate
      proliferation of astroglial cells, have no effect on phosphatidylinositol-3
      kinase activity. Addition of 1 nM PDGF, 10 nM IGF1 or 100 nM EGF to the culture
      medium rapidly stimulated phosphatidylinositol-3 kinase activity which declined
      slowly after 2 min. The stimulation of phosphatidylinositol-3 kinase increased
      with growth factor concentration. The maximum increase in phosphatidylinositol-3
      kinase activity occurred with 50 nM IGF1, 1 nM PDGF or 100 nM EGF. Since insulin
      was active only at high concentration (1 microM), its effect was probably
      mediated through IGF1 receptors and not through insulin receptors. Treatment with
      IGF1-plus-EGF, had an additive effect on PI(3)-kinase activity, PDGF-plus-IGF1
      did not. IGF1 and PDGF, to a lesser degree, also increased the
      phosphatidylinositol-3 kinase activity associated with pp60c-src protein.
      Immunoblots performed with an antibody directed against the p85-subunit of the
      phosphatidylinositol-3 kinase confirmed that IGF1 increased the number of
      phosphatidylinositol-3 kinase molecules associated with phosphotyrosine
      containing proteins or with c-src protein. Each growth factor affects in a
      different manner the association of phosphatidylinositol-3 kinase with
      phosphotyrosine-containing proteins and with c-src protein and thus probably
      modulates intracellular signals downstream of phosphatidylinositol-3 kinase in
      astroglial cells.

PMID- 7526916
TI  - Inhibition of phospholipase D of human platelets by protein tyrosine kinase
      inhibitors.
AB  - Protein tyrosine kinases (PTKs) of the src family are thought to play an
      important role in platelet signal transduction, but little is known about the
      targets of these enzymes in platelets. We determined that exposure of human
      platelets to pervanadate, an inhibitor of protein tyrosine phosphatases, caused
      an increase in the activity of phospholipase D (PLD), an enzyme that might be
      involved in signaling events leading to aggregation or secretion. To further
      investigate whether tyrosine phosphorylation is a step in the pathway of
      activation of PLD in response to thrombin, we tested the effects of a series of
      PTK inhibitors on the activity of platelet PLD. PLD was activated in response to
      0.3 U/ml thrombin, and this activation was reduced by several of the PTK
      inhibitors, especially genistein, methyl 2,5-dihydroxycinnamate (MDHC), ST271,
      and the tyrphostins A25 and A47. In saponin-permeabilized platelets, we observed
      a marked inhibition of GTP-gamma S-stimulated PLD by many of the PTK inhibitors,
      consistent with the possibility that PTKs are involved in the regulation of PLD
      activity by a G-protein or small GTP-binding protein. MDHC did not affect PLD
      activity in permeabilized cells, which suggests that this compound might inhibit
      PLD in intact platelets via another pathway. The inhibitors were also tested for
      their effects on the phosphorylation of a peptide substrate of src-family PTKs in
      a platelet membrane preparation and in permeabilized platelets. Several of the
      compounds partially inhibited peptide phosphorylation in the membrane preparation
      and in permeabilized platelets, most notably ST271, ST638, and tyrphostin
      A25.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526919
TI  - P56lck: a transducing protein that binds to SH2 containing proteins and to
      phosphotyrosine containing proteins.
AB  - In T lymphocytes, several proteins are rapidly phosphorylated on tyrosine after
      stimulation. In this study we examine the ability of tyrosine phosphorylated
      proteins from Jurkat T cells stimulated by CD2 or T cell receptor (TcR)-CD3 to
      interact with the src homology 2 (SH2) domains from p56lck (Lck). Our data show
      that the patterns are different depending on the stimulation. The specificity of
      the interactions was assessed by blocking experiments with high affinity
      phosphotyrosine [Y(P)] peptides. Phosphorylation experiments suggest that one or
      several kinases are able to interact with the SH2 from Lck. On the other hand,
      full length Lck overexpressed in Sf9 cells, which is tyrosine-phosphorylated at
      least on two sites, can interact in vitro with the SH2 from Lck, phospholipase C
      (PLC)-gamma 1, p85 (the regulatory subunit of phosphatidyl-inositol-3 kinase
      (PI3K)) and Nck and with the full length Grb2. These data give additional support
      to the idea that Lck is an important signal transducing molecule in lymphocytes.

PMID- 7526921
TI  - Molecular pharmacology of the AMPA agonist, (S)-2-amino-3-(3-hydroxy-5-phenyl-4
      isoxazolyl)propionic acid [(S)-APPA] and the AMPA antagonist, (R)-APPA.
AB  - The heterocyclic analogue of (S)-glutamic acid, (S)-2-amino-3-(3-hydroxy-5-methyl
      4-isoxazolyl)propionic acid [(S)-AMPA] is a potent and selective AMPA receptor
      agonist, whereas the enantiomeric compound, (R)-AMPA, is virtually inactive. We
      have previously characterized (RS)-2-amino-3-(3-hydroxy-5-phenyl-4
      isoxazolyl)propionic acid [(RS)-APPA] as a partial AMPA receptor agonist showing
      about 60% of the efficacy of (RS)-AMPA. This partial agonism produced by (RS)
      APPA is, however, only apparent, since resolution of (RS)-APPA has now been shown
      to provide the full AMPA receptor agonist, (S)-APPA, whereas (R)-APPA is a non-N
      methyl-D-aspartic acid (non-NMDA) receptor antagonist showing preferential AMPA
      blocking effects. In agreement with classical theories for competitive
      interaction between agonists and antagonists, the efficacy of depolarizations
      produced by (S)-APPA in the rat cortical wedge preparation was shown to be
      progressively reduced with increasing molar ratios of (R)-APPA/(S)-APPA. These
      compounds and the competitive antagonists (RS)-2-amino-3-(3-carboxymethoxy-5
      methyl-4-isoxazolyl)propionic acid [(RS)-AMOA], 6-cyano-7-nitroquinoxalin-2,3
      dione (CNQX) and 6-nitro-7-sulfamoylbenzo(f)quinoxalin-2,3-dione (NBQX) were also
      tested in [3H]AMPA and [3H]CNQX binding systems, the latter ligand being used in
      the absence or presence of thiocyanate ions. On the basis of these studies it is
      suggested that (RS)-AMPA and the AMPA agonist (S)-APPA interact with a high
      affinity receptor conformation, whereas the competitive antagonists (RS)-AMOA and
      (R)-APPA, derived from these agonists, preferentially bind to a low-affinity AMPA
      receptor conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526922
TI  - Selective expression of CD44 messenger RNA splice variants in four high grade
      human brain tumour cell lines.
AB  - Changes in CD44 transcripts have been previously found to be associated with
      metastasis in animal models. The purpose of this study was to investigate CD44V
      changes in four well established high grade human brain tumor cell lines, known
      to possess prominent invasive behavior. In Northern blot analysis, CD44S and
      CD44V were expressed strongly in three high-grade glioblastoma multiforme cell
      lines (GBM 8401, GBM 8909, GBM 8804) and one malignant meningioma cell line
      (IOMM). By RT-PCR and blot hybridization, three variant transcripts (650 bps, 850
      bps, and 1,000 bps) were detected in GBM 8804 and two isoform transcripts (650
      bps, 850 bps) were recognized in GBM 8401 and 8909. Further, in a malignant
      meningioma cell line (IOMM), only one weak isoform (650 bps) was detected.
      However, by Northern blot analysis, neither CD44S or CD44V could be expressed in
      normal brain and meningeal tissue. These results indicate that discrete CD44 mRNA
      splice variants are expressed in high grade glial cell tumors and malignant
      meningioma and suggest a possible role in the invasion of malignant brain tumors.

PMID- 7526920
TI  - Distinct heterotrimeric GTP-binding-proteins act in series to control the
      exocytotic machinery in chromaffin cells.
AB  - Regulated exocytosis requires both calcium and MgATP. Although the biochemical
      events responsible for ATP-dependent calcium-activated secretion have not been
      elucidated yet, some progress has been made in determining the relative order of
      the ATP- and calcium-dependent steps. Studies on permeabilized secretory cells
      have shown that MgATP acts before calcium and maintains the secretory apparatus
      in a "primed" state. In this paper, we examine the possible role of
      heterotrimeric G-proteins in these two steps of exocytosis in permeabilized
      chromaffin cells. We show that mastoparan and other activators of heterotrimeric
      G-proteins inhibit the MgATP-dependent reaction, but stimulate the late calcium
      dependent step of exocytosis. Non-hydrolyzable GTP analogues (GTP-gamma-S and GMP
      PNP) mimic the dual effects of mastoparan on secretion, but with different
      potencies, suggesting the involvement of two distinct heterotrimeric G-proteins
      in regulated exocytosis. GPAnt-2, a substance P related peptide known to inhibit
      the stimulation of Gi and Go by mastoparan, reverses, in a dose-dependent manner,
      both the inhibitory and stimulatory effects of mastoparan on secretion. These
      results indicate that two distinct heterotrimeric G-proteins from the Gi/o family
      may act in series in the exocytotic pathway in chromaffin cells: one controls the
      ATP-dependent priming step, whereas the second is involved in the late calcium
      dependent fusion step which does not require ATP.

PMID- 7526917
TI  - The protein tyrosine kinase pp60c-src is activated upon platelet stimulation.
AB  - Stimulation of human platelets causes a dramatic increase in phosphorylation of
      various proteins at tyrosine residues. The abundance of protein tyrosine kinases
      of the src-family in platelets, particularly pp60c-src, suggests an important
      role of these kinases in response to stimulation events. We have shown that pp60c
      src is activated on agonist-induced platelet stimulation with respect to its
      substrate affinity. This was accompanied by phosphorylation of pp60c-src at Ser
      12, a residue which is phosphorylated by PKC. Inhibition of PKC with a specific
      inhibitor, Ro-31-8220, suppressed thrombin-induced translocation of pp60c-src to
      the cytoskeleton. On the basis of our data, we suggest that the cytoskeletal
      association of pp60c-src is dependent on phosphorylation of pp60c-src at Ser-12
      by PKC. Phosphorylation at Ser-12 in the membrane-binding domain might be the
      signal that displaces pp60c-src from the plasma membrane and, accompanied with
      the increased substrate affinity, facilitates phosphorylation of putative
      substrates.

PMID- 7526923
TI  - Cloning and characterization of a cluster of genes coding for 5S rRNA and three
      tRNAs from Azospirillum lipoferum.
AB  - A genomic library was constructed from a HindIII digest of Azospirillum lipoferum
      chromosomal DNA in the HindIII site of pUC19. From the library, a clone, pALH64,
      which showed strong hybridization with 3' end labeled A. lipoferum total tRNAs
      and which contains a 2.9 kb insert was isolated and restriction map of the insert
      established. The nucleotide sequence of a 490 bp HindIII-HincII subfragment
      containing a cluster of genes coding for 5S rRNA, tRNA(Val)(UAC), tRNA(Thr)(UGA)
      and tRNA(Lys)(UUU) has been determined. The gene organization is 5S rRNA (115
      bp), spacer (10 bp), tRNA(Val) (76 bp), spacer (3 bp), tRNA(Thr) (76 bp), spacer
      (7 bp) and tRNA(Lys) (76 bp). Hybridization experiments using A. lipoferum total
      tRNAs and 5S rRNA with the cloned DNA probes revealed that all three tRNA genes
      and the 5S rRNA gene are expressed in vivo in the bacterial cells.

PMID- 7526924
TI  - Analysis of the mouse and rat CFTR promoter regions.
AB  - To gain insights into the regulation of the mouse and rat cystic fibrosis
      transmembrane conductance regulator (CFTR) genes, we cloned and sequenced their
      respective upstream promoter regions. DNA sequence analysis from either side of
      exon 1 revealed a complete divergence from the human DNA sequence except for
      three DNA motifs which consist of a 34 bp stretch and two intron specific
      elements. Highlights of both the rat and mouse promoter sequences include an
      extensive purine rich stretch, a Y-box motif and putative Sp1, AP1 sites.
      Transfection of mouse promoter deletional constructs into expressing and non
      expressing CFTR murine cell lines revealed that the Pu.Py stretch and the Y-box
      act, respectively, as negative and positive elements of basal transcription that
      confer no apparent tissue specificity.

PMID- 7526925
TI  - Analysis of mutations and alternative splicing patterns in the CFTR gene using
      mRNA derived from nasal epithelial cells.
AB  - Ten to fifteen percent of CF chromosomes carry mutations which are not detected
      by routine screening of the CFTR gene for known mutations. Many techniques have
      been used to screen the CFTR gene for these remaining mutations. Most of the
      methods use genomic DNA, and since the CFTR gene contains 27 exons, are
      necessarily labour intensive. We have screened the entire coding region of CFTR,
      by chemical cleavage of 7 overlapping segments of amplified cDNA. Using this
      method we have identified 4 sequence changes which had not been detected by
      screening genomic DNA, and successfully detected 10 out of 13 known mutations. In
      addition, we have identified 8 alternatively spliced forms of CFTR mRNA, 4 of
      which have not been described previously. These include transcripts lacking a)
      exon 3, b) exons 2 + 3, c) exons 9 + 12, and d) the final 357 bp of exon 15 as a
      result of use of the cryptic splice donor site CA2863/GTTCGT).

PMID- 7526927
TI  - Identification of the L927P and delta L1260 mutations in the CFTR gene.

PMID- 7526926
TI  - A novel mutation of Leu122 to Phe at a highly conserved hydrophobic residue in
      the helix initiation motif of keratin 14 in epidermolysis bullosa simplex.

PMID- 7526929
TI  - A novel mutation (G1249R) in exon 20 of the CFTR gene.

PMID- 7526930
TI  - Newly developed ultrasonic aspirator and its application for endoscopic surgery.
AB  - The authors have developed an ultrasonic aspirator to assist in urologic
      endoscopic surgery. It appeared that ultrasonic aspiration of bladder tumors was
      clinically efficient in transurethral surgery. Tumors 1 to 2 cm in diameter could
      be aspirated completely with this instrument alone. The application of the
      ultrasonic aspirator, which has also been designed with a coagulating function,
      to laparoscopic lymphadenectomy was evaluated. A special probe sheath was used to
      insulate it when using coagulation current. During operation, perivascular fatty
      tissue was removed safely with the aspirator. In the near future, the ultrasonic
      aspirator will be one of the most effective tools in laparoscopic surgery.

PMID- 7526928
TI  - Development of RNA-SSCP protocols for the identification and screening of CFTR
      mutations: identification of two new mutations.
AB  - A strategy is described that allows a rapid and accurate identification and
      screening of cystic fibrosis gene mutations. It consists of setting up and
      developing RNA single strand conformation polymorphism (rSSCP) protocols, a
      technique based on the large repertoire of secondary structure of single-stranded
      RNA. By incorporating the T7 phage promoter sequence into PCR primers, it is
      possible to carry out rSSCP and compare it to standard single-strand conformation
      polymorphism (SSCP). Several parallel tests indicate that rSSCP detects a higher
      fraction of single base changes, and is less time consuming than SSCP since it
      requires only one fairly short electrophoretic run. Using this technique we were
      able to identify two new splicing mutations in introns 5 (711 + 5G-->A) and 10
      (1717-8G-->A) of the CFTR gene.

PMID- 7526932
TI  - The cystic fibrosis mutation (delta F508) does not influence the chloride channel
      activity of CFTR.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a
      phosphorylation-regulated Cl- channel. In most mammalian cells, the functional
      consequences of the most common CF mutation, delta F508-CFTR, cannot be assessed
      as the mutant protein undergoes biosynthetic arrest. However, function can be
      studied in the baculovirus-insect cell expression system where delta F508-CFTR
      does not appear to undergo such arrest. Our results show that phosphorylation
      regulated Cl- channel activity of delta F508-CFTR is similar to that of wild-type
      CFTR. This observation was confirmed in comparative studies of purified delta
      F508-CFTR and CFTR reconstituted in planar lipid bilayers. Therefore, we suggest
      that this common mutation does not result in a significant alteration in CFTR
      function.

PMID- 7526933
TI  - A missense mutation in the rod domain of keratin 14 associated with recessive
      epidermolysis bullosa simplex.
AB  - Epidermolysis bullosa simplex (EBS) is a group of epidermal blistering diseases
      almost invariably transmitted as a dominant trait, which has recently been shown
      to arise from mutations in keratins 14 and 5 (K14 and K5). We describe a family
      with recessive EBS in which the disease is tightly linked to the substitution of
      the highly conserved glutamic acid-144 to alanine in the first helical segment of
      the rod domain of keratin 14. In contrast, linkage with keratin 5 was excluded.
      The loss of an ionic interaction with keratin 5 is likely to affect K14-K5
      heterodimer formation. Our data suggest that this mutation underlies EBS in our
      family, and that mutations in keratin genes may impair the mechanical integrity
      of basal keratinocytes in a recessive as well as dominant fashion.

PMID- 7526931
TI  - Low-power laser radiation for the treatment of benign prostatic hyperplasia:
      initial clinical experience.
AB  - Fifteen patients with significant bladder outlet obstruction secondary to benign
      prostatic hyperplasia (BPH) were entered in a Phase II open pilot study designed
      to evaluate the effectiveness of a low-power-slow-heating (15 W x 180 seconds)
      laser regimen. Laser prostatectomies were performed with a right-angle firing
      neodymium:YAG laser fiber. Perioperative morbidity was minimal. Nine patients
      (60%) were able to void on their own within 72 hours after the procedure. The
      mean postoperative need for catheter drainage was 3.8 days (range 1 to 12). With
      a mean follow-up of 5 months (range 3-15 months), the improvement of the mean
      peak urinary flow rate was from 12.8 to 29 mL/sec, the mean postvoiding residual
      volume was reduced from 100 to 35 mL, and the AUA Symptom Score improved from
      28.5 to 6. None of the patients required retreatment, and all the patients were
      pleased with the outcome. These results suggest that the laser regimen used in
      our study is safe and effective for the treatment of BPH.

PMID- 7526935
TI  - Contralateral rotations induced by intrastriatal injections of agonists of
      excitatory amino acid receptors.
AB  - NMDA (100, 250 and 500 ng/0.5 microliters), kainic acid (50 and 100 ng/0.5
      microliters) and AMPA (500 and 1000 ng/0.5 microliters), injected unilaterally
      into the ventrolateral part of the intermediate region of the caudate-putamen of
      rats, induced contralateral rotations. It is proposed that stimulation of NMDA,
      kainate and AMPA receptors present on strionigral neurons evokes an
      "antiparkinsonian effect".

PMID- 7526936
TI  - Determination of antigen-antibody affinity by immunocapillary electrophoresis.
AB  - The use of affinity capillary electrophoresis for the characterization of antigen
      antibody interactions (immunocapillary electrophoresis) is shown using monoclonal
      antibodies against phosphotyrosine as a model system. The influence of the
      interaction kinetics on the peak profiles was demonstrated in experiments with
      addition of phosphotyrosine to the electrophoresis buffer. One of the two
      antibodies that were tested exhibited peak broadening while the other showed no
      change in peak shape but had a decreased mobility proportional to the amount of
      phosphotyrosine present. The migration shifts which were of the order 0.05 to
      0.15 min at 439 V/cm were a consequence of the antibody-antigen complexes having
      a slower mobility than the non-complexed antibody. On the basis of measurement of
      migration shifts at different antigen concentrations, dissociation constants were
      estimated and shown to be independent on the applied field strength. Thus, when
      certain requirements are fulfilled, immuno-capillary electrophoresis is a fast
      and simple method for establishing binding characteristics of unlabelled antigen
      and antibody molecules under non-denaturing conditions and consumes minute
      amounts of sample.

PMID- 7526934
TI  - Studies on antidepressant action of a new oxazolidinone derivative AS-8.
AB  - On the basis of previous laboratory studies AS-8 was suggested to possess
      antidepressant-like activity. Forced swim test, learned helplessness and conflict
      Vogel's test were performed after three prior administrations of AS-8 (24, 5 and
      1 h before the test). The data have shown that AS-8 produces moderate
      antidepressant effect but did not induce anxiolytic-like action. Biochemical data
      revealed increased brain 5-HT and 5-HIAA levels following AS-8 administration.
      The combined treatment of rats with AS-8 (100 mg/kg) and amitriptyline (5 mg/kg)
      or desipramine (1.25 mg/kg) significantly stimulated active behavior in the
      forced swim test above the level obtained with each of the drug given separately.
      The present data suggest the potential antidepressant efficacy of AS-8 in
      conjunction with small doses of tricyclic antidepressants.

PMID- 7526937
TI  - Mixed polymer networks in the direct analysis of pharmaceuticals in urine by
      capillary electrophoresis.
AB  - Two-component polymer mixtures of polyethylene oxide-polydextran have been
      investigated as unique separation media for capillary electrophoresis. The
      effects of concentration of the individual polymers and their mixtures on the
      electroosmotic velocity and electrophoretic mobility of small pharmaceutical
      compounds were investigated. The molecular masses of polymers, buffer
      concentrations and percentages of organic solvents and cyclodextrins were varied
      to explore their effects on the separation process. The plate height against
      field strength curves were also generated for a better understanding of the
      kinetic processes involved. The two-component polymer mixtures were found as
      stable and selective media for the analysis of an anti-ulcer drug famotidine
      directly in untreated urine.

PMID- 7526938
TI  - Obesity: a new feature of WAGR (del 11p) syndrome.
AB  - A 6-year-old girl with del(11)(p14p12) is reported. This girl has the multiple
      congenital anomalies that defines the WAGR syndrome (aniridia, external genital
      hypoplasia and severe mental retardation). She has, in addition, very severe
      obesity (+10 SD) which is not a feature usually described with WAGR association.

PMID- 7526939
TI  - Larsen syndrome in siblings with consanguineous parents.
AB  - Two siblings with Larsen syndrome and consanguineous parents are described, both
      with multiple joint dislocations and the typical facial appearance. Short stature
      is marked in both children and one had a diaphragmatic hernia which has not been
      previously described in this condition.

PMID- 7526940
TI  - Immunohistochemical characterization of the shell and core territories of the
      nucleus accumbens in the rat.
AB  - The nucleus accumbens in the rat has been parcelled into shell and core
      subdivisions. Despite accumulating evidence for such a division of the nucleus
      accumbens, these territories have not been delineated throughout the rostrocaudal
      extent of the nucleus. In the present study, an attempt has been made to
      delineate the shell and core using the distribution of calcium-binding protein
      immunoreactivity, substance P immunoreactivity and acetylcholinesterase activity
      in transverse and horizontal sections through the nucleus accumbens. It was found
      that the pattern of calcium-binding protein immunoreactivity provides the most
      unequivocal criterion to divide the nucleus accumbens into a ventral and medial,
      peripheral shell displaying low to moderate immunostaining, and a more laterally
      and dorsally located, strongly stained inner core. In most parts of the nucleus,
      borders seen in the calcium-binding protein immunoreactivity pattern can also be
      recognized in the distributions of substance P immunoreactivity and
      acetylcholinesterase activity. It is concluded that the shell occupies most of
      the rostral part of the nucleus accumbens, whereas rostrally the core is
      represented only in the most lateral part. Differences in staining intensities
      for all three markers indicate that both the shell and core have a heterogeneous
      structure. Patterns of connectivity appear to support the division of the nucleus
      accumbens as indicated by calcium-binding protein immunoreactivity in the present
      study.

PMID- 7526941
TI  - Intracellular messengers contributing to persistent nociception and hyperalgesia
      induced by L-glutamate and substance P in the rat formalin pain model.
AB  - The contribution of the intracellular messengers nitric oxide, arachidonic acid
      and protein kinase C to persistent nociception in response to tissue injury in
      rats was examined following the subcutaneous injection of formalin into the
      hindpaw. Formalin injury-induced nociceptive behaviours were reduced by
      intrathecal pretreatment with inhibitors of nitric oxide synthase (NG-nitro-L
      arginine methyl ester, L-NAME), arachidonic acid (dexamethasone) or protein
      kinase C [protein kinase C (19-26) and 1-95-(isoquinolinesulphonyl)-2
      methylpiperazine dihydrochloride, H-7]. Each of these agents affected the tonic,
      but not the acute, phase of the formalin response. Furthermore, none of these
      agents affected mechanical or thermal flexion reflex thresholds in rats not
      injected with formalin. Conversely, formalin-induced nociceptive responses were
      enhanced by stimulators of nitric oxide (sodium nitroprusside), arachidonic acid
      metabolism (arachidonic acid) or protein kinase C [(+/-)-1-oleoyl-2-acetyl
      glycerol], and were slightly reduced by inositol trisphosphate. Mechanical
      flexion reflexes were also reduced by arachidonic acid, while thermal flexion
      reflexes were reduced after treatment with sodium nitroprusside, arachidonic acid
      or [(+/-)-1-oleoyl-2-acetyl-glycerol]. The enhancement of formalin nociceptive
      behaviours (hyperalgesia) in rats treated with L-glutamate or substance P was
      reversed by pretreatment with inhibitors of nitric oxide (L-NAME), arachidonic
      acid (dexamethasone) or protein kinase C (H-7). The results suggest that central
      sensitization and persistent nociception following formalin-induced tissue
      injury, and the hyperalgesia in the formalin test induced by L-glutamate and
      substance P, are dependent on the intracellular messengers nitric oxide,
      arachidonic acid and protein kinase C.

PMID- 7526943
TI  - Modulation of beta 2-adrenoceptors in human lymphocytes by in vitro stimulation
      with mediators.
AB  - Since Szentivanyi established the beta-adrenergic theory, many attempts have been
      made to explain the dynamics of bronchial hyperreactivity and cytotropic allergic
      reaction by this mechanism. In previous work, we found that beta-adrenoceptor
      numbers were decreased in symptomatic patients and after specific antigenic
      exposure. As a result, we postulated that this might be due to mediator activity.
      Blood was extracted from 46 healthy donors for this study. Radioligand [125I]
      iodocyanopindolol was used for beta-adrenoceptor determination in peripheral
      blood lymphocytes following Brodde's method. Student's t test was used for
      statistical analysis. beta-Adrenoceptor number was determined before and after
      exposure to mediators (histamine, PAF, LTD4), and after melittin (phospholipase
      A2, PLA2, activator) exposure. A significant decrease was obtained after
      histamine (p < 0.05), LTD4 (p < 0.05) and melittin (p < 0.001) exposure; PAF did
      not modify the number of beta-adrenoceptors. In conclusion, our results confirm
      that down-regulation of beta-adrenoceptors can be induced by mediator release.

PMID- 7526944
TI  - Out of the past.

PMID- 7526942
TI  - Ca2+/calmodulin-dependent nitric oxide synthase in Apis mellifera and Drosophila
      melanogaster.
AB  - NADPH diaphorase (NADPHd) is a marker enzyme for nitric oxide (NO)-producing
      cells in vertebrates. This paper investigates the relationship between NADPHd and
      the NO-producing enzyme NO synthase (NOS) in neuronal tissue of Apis and
      Drosophila, two insects used for studying learning. First, the NOS and the NADPHd
      in both species were characterized biochemically. The fixation-insensitive NADPHd
      activity, which accounts for the staining in NADPHd histochemistry, co-purifies
      with the insect Ca2+/calmodulin-dependent NOS. Formation of NO from L-arginine
      depends on NADPH, and half-maximal stimulation is observed with 0.3 microM Ca2+.
      NOS is competitively inhibited by methyl-L-arginine and nitro-L-arginine, with Ki
      of 1.7 and 1.9 microM, respectively. The co-purification and the competitive
      inhibition of NOS by the NADPHd substrate, nitro blue tetrazolium (NBT), are
      proof that in insects the enzyme responsible for fixation-insensitive NADPHd
      activity is nitric oxide synthase. Second, the NOS activity was quantified in
      distinct neuropiles and the NO-producing neuropiles were visualized using NADPHd
      histochemistry. In both species the highest NOS activity is found in the
      chemosensory neuropiles of the antennal lobes, intermediate activity in the
      neuropiles of the central brain and by far the lowest NOS activity in the visual
      neuropiles. Although in both species the Kenyon cell somata of the mushroom
      bodies show no detectable staining, the neuropiles of the mushroom bodies of
      Drosophila and Apis show a distinct staining. The staining pattern of NOS in both
      species is different to that of all known neurotransmitters.

PMID- 7526946
TI  - Serous oligocystic and ill-demarcated adenoma of the pancreas: a variant of
      serous cystic adenoma.
AB  - Serous cystic tumours of the pancreas are uncommon and are usually classified as
      microcystic adenomas (MCA). As new types of serous cystic tumours of this organ
      have been reported we reviewed a series of 14 lesions and from macroscopic
      findings two groups were distinguished: ten tumours revealed the features of MCA,
      while four were clearly distinct from MCA. Grossly, the latter tumours showed
      only few cysts which were irregularly assembled in fibrous stroma. On the cut
      surface, there was neither a central stellate scar nor a circumscribed tumour
      border, features characterizing MCA. Microscopically, the cysts were lined by
      cuboidal, non-mucin-producing cells. Immunocytochemical staining for cytokeratins
      7, 8, 18 and 19 revealed a ductal phenotype. All non-MCA were found in the head
      of the pancreas and three of them occurred in men. There were no tumour
      recurrences or signs or malignant transformation after resection (mean follow-up,
      2.9 years). These results suggest that there are serous cystic tumours distinct
      from MCA which may represent another variant of the category of serous cystic
      adenomas of the pancreas. We propose the term serous oligocystic and ill
      demarcated adenoma (SOIA) for these tumours. It is possible that the recently
      described macrocystic sybtype of serous cystadenoma and SOIA and variants of the
      same tumour.

PMID- 7526945
TI  - Bacteriophage epitope libraries. The generation of specific binding proteins and
      peptides in vitro.
AB  - New concepts and methodologies that can be used to generate proteins, such as
      specific variable regions of immunoglobulins and other binding peptides in an in
      vitro selection system are reviewed. These technologies can also be used to alter
      the kinetics, affinity and avidity of various binding interactions. The nature of
      epitopes recognized by specific antibodies or receptors can be delineated using
      selected epitopes displayed on bacteriophages. The basic principles of the
      technology is predicted upon the belief that if one has a large enough variety of
      keys, one can open any given lock. The range of utility of these systems to
      generate new reagents will impact upon the development of new diagnostic and
      therapeutic reagents. This technology should allow for a much wider range of
      probes which may have increased binding capacity and allow the development of
      more sensitive assays with higher signal to noise ratios. These reagents can be
      produced more efficiently without the use of animals and will be used in
      diagnostic and experimental pathology. This brief review presents a concise
      description of the concepts and uses of this new technology. Selected references
      and reviews are given as sources for further details.

PMID- 7526947
TI  - Localisation of hyaluronate (HA) in primary tumors and nude mouse xenografts of
      human pancreatic carcinomas using a biotinylated HA-binding protein.
AB  - A biotinylated hyaluronate (HA)-binding protein isolated from bovine cartilage
      was used to analyze the distribution of HA in nude mouse xenografts derived from
      human pancreatic adenocarcinoma cell lines as well as in primary human pancreatic
      adenocarcinomas. The most reproducible results for the localisation of HA were
      obtained using cryostat sections. When the biotinylated HA-binding protein was
      applied to histological sections of nude mouse xenografts, the specific staining
      found could be inhibited by preincubating the HA-binding protein with an excess
      of HA or by hyaluronidase treatment of the tissue before staining. The highest HA
      concentration was found at the tumor boundaries, while in the central part of the
      tumor staining was slight or absent. In cryostat sections of primary tumors HA
      was found predominantly in the connective tissue immediately around tumor cells
      or at the border between the tumor and normal pancreatic tissue.

PMID- 7526949
TI  - Angiogenesis: potential therapy for ischaemic disease.
AB  - The discovery of polypeptide mitogens capable of stimulating angiogenesis has
      inspired research addressing the potential of these agents in the treatment of
      ischaemic syndromes. Ischaemia or necrosis with associated inflammation has been
      found to increase the production of growth factors and receptor response.
      Administration of various exogenous angiogenic agents by several routes has
      resulted in enhanced growth of collateral vessels in animal models of myocardial,
      peripheral arterial, and cerebral insufficiency. Therapeutic angiogenesis may
      have an immense clinical potential.

PMID- 7526948
TI  - The chemical morphology of extracellular matrix in experimental rat liver
      fibrosis resembles that of normal developing connective tissue.
AB  - The time course of development of extracellular matrix (ECM) in experimentally
      induced fibrosis (thioacetamide administration followed for 12 weeks or bile duct
      ligation for 8 weeks) in adult rats was examined by light and electron
      microscopy, using Alcian blue or Cupromeronic blue staining for sulphated
      proteoglycans (PGs) in critical electrolyte concentration techniques.
      Proteodermatan sulphate (PDS) was regularly observed at the gap zone of the
      collagen fibrils. Morphometry of uranyl acetate-stained collagen fibrils,
      polarity of their banding patterns (a-e), statistics of d/e band occupancies by
      PDS, and lengths and thicknesses of PG filaments were quantified. Biochemical
      analyses showed that the ECM components collagen, hyaluronan, chondroitin and
      dermatan sulphates increased by 5-10 fold, roughly in parallel, as did heparan
      sulphate and DNA. Water and lipid contents also increased sharply. Thioacetamide
      treatment was much slower than bile duct ligation in producing fibrotic changes
      of equal severity. Sulphation of anionic glycosaminoglycans (AGAGs) decreased
      with increasing severity of fibrosis. Biochemical and ultrastructural methods
      correlated well. The large increase in dermatan sulphate was quantitatively as
      expected, given that it is collagen fibril surface-associated, and there was an
      increase of collagen content together with a decrease in fibril thicknesses. The
      increase in DNA reflected the marked increase in cell numbers in fibrotic livers.
      The chemical morphology of the new connective tissue closely resembled that in
      e.g. developing young tendon, in that fibrils were thinner, and AGAG levels were
      higher. The collagen fibrils were often disarranged, rather than ordered and
      parallel as in normal ECM. No other indication of abnormality in the new ECM was
      obtained.

PMID- 7526950
TI  - The effects of a long term treatment with cyclophosphamide on the thymus and on
      some blood parameters in Wistar rats.
AB  - Adult Wistar rats of both sexes were treated with Cyclophosphamide (a Romanian
      product), for 12 month. The Cyclophosphamide was given in the food, in 3
      different doses (0.31, 1.25, respectively 2.5 mg/kg body weight). The
      modifications produced in the thymus and blood plasma were dose and sex
      dependent, and they emphasize an alteration in the protein metabolism, which is
      not accompanied by an involuntion of the thymus itself.

PMID- 7526951
TI  - Ultrastructure of the Ranvier's node in vincristine neuropathy.
AB  - Paranode-node-paranode regions of the nerve fibre interact in a fundamental
      manner with the transport of axoplasmic material. The aim of the study was to
      examine the ultrastructure of Ranvier's node in sciatic nerve of rabbits treated
      with vincristine. The results showed accumulation of organelles in Ranvier's
      nodes of affected animals. Organelles arrested in this region disturbed each
      other and degenerated. Some of them were sequestered from the axon by Schwann
      cell fingers and terminal loops, but often this process was not sufficient to
      prevent nerve fibre against degeneration. In conclusion our results provided
      evidence that Ranvier's node become locus minoris resistentiae in vincristine
      affected nerve fibers.

PMID- 7526953
TI  - TA3/St, but not TA3/Ha, mammary carcinoma cell adhesion to hepatocytes is
      mediated by alpha 5 beta 1 interacting with surface-associated fibronectin.
AB  - The cell lines TA3/Ha and TA3/St are derived from the same tumor, grow both in
      suspension and form liver metastases upon intraportal injection. We have studied
      the interaction of these cell lines with hepatocytes, which is likely to be
      relevant for liver metastasis formation. Recently we have shown that the integrin
      alpha 6 beta 4 is involved in adhesion of TA3/Ha cells to hepatocytes. However,
      we show here that the alpha 6 beta 4-specific antibodies, that inhibit adhesion
      of TA3/Ha cells, did not affect adhesion of TA3/St cells to hepatocytes. The beta
      4 subunit, present at high levels on TA3/Ha cells, was found to be expressed at a
      much lower level by TA3/St cells. In contrast, TA3/St cells express much more of
      the beta 1-integrin subunit than TA3/Ha cells. We assessed whether these
      differences in integrin expression are responsible for the different adhesion
      mechanisms used by these cell lines. We show that alpha 5 beta 1, which is
      expressed by TA3/St cells, and not by TA3/Ha cells, is involved in TA3/St
      adhesion to fibronectin that is associated with the hepatocyte surface. Since
      fibronectin is the main extracellular matrix component present on the hepatocyte
      surface underneath the sinusoidal endothelium, alpha 5 beta 1 may be particularly
      important for metastasis formation in the liver, as compared to other organs.

PMID- 7526952
TI  - Expanding roles for alpha 4 integrin and its ligands in development.
AB  - Interaction of alpha 4 integrins with vascular cell adhesion molecule-1 (VCAM-1)
      is classically important for immune function. However, we found recently that
      these receptors have a second role, in embryogenesis, where they mediate cell
      cell interactions that are important for skeletal muscle differentiation. Here,
      we present evidence of an expanding role for these receptors in murine
      development. alpha 4 and VCAM-1 were found at embryonic sites of hematopoiesis,
      suggesting a role for these receptors during embryogenesis that parallels their
      hematopoietic function in adult bone marrow. During angiogenesis in the lung,
      alpha 4 and VCAM-1 were found on mesenchyme that gives rise to vascular
      endothelium and smooth muscle. alpha 4 persisted on the smooth muscle and the
      endothelium of newly forming vessels where it colocalized with its extracellular
      matrix ligand, fibronectin (FN). These patterns suggest several roles for alpha 4
      integrins and their ligands in angiogenesis. alpha 4 was also found on neural
      crest derivatives where it colocalized with FN. alpha 4 was expressed selectively
      on cells in the dorsal root ganglia: it was apparent along ventral projections,
      but absent from dorsal projections, suggesting that alpha 4 integrins could be
      involved in defining neuronal fates. Although VCAM-1 was not expressed on most
      neural crest derivatives, it was found in the neural crest-derived outflow tract
      of the embryonic heart, where it colocalized with alpha 4. These results imply
      that alpha 4 integrins and their ligands could be important for migration or
      differentiation of neural crest. alpha 4 was also expressed on embryonic retina
      and FN was found on inductive mesenchyme surrounding the eye, suggesting a role
      for these proteins in eye development. Finally, based on their patterns of
      expression, we conclude that VCAM-1 only participates in a subset of interactions
      involving alpha 4 integrins, whereas FN appears to be the more general ligand.

PMID- 7526954
TI  - Expression of P-selectin on endothelial cells is upregulated by LPS and TNF-alpha
      in vivo.
AB  - P-selectin is an endothelial cell adhesion molecule which mediates the binding of
      neutrophils and monocytes. Its appearance at the cell surface can be induced
      within minutes by histamine and thrombin which rapidly stimulate the transport of
      P-selectin from intracellular storage granules to the plasma membrane. We have
      recently found a second regulation mechanism for P-selectin on mouse endothelioma
      cells. Like E-selectin, P-selectin is also regulated at the level of
      transcription. Both selectins are induced by LPS or TNF-alpha with a maximal
      expression level at the cell surface 3-4 h after stimulation. Here, we report
      that this up-regulation of the synthesis of P-selectin also occurs in vivo in
      endothelium of the mouse. Analysing brain tissue, which is devoid of constitutive
      expression of P-selectin, we found that LPS and also TNF-alpha strongly induce
      the expression of P-selectin on all venular endothelial cells of the
      leptomeninges and, at a weaker level, on some blood vessels of the brain
      parenchyma. Induction of P-selectin expression could also be observed in tissues,
      such as the tongue, where P-selectin is constitutively expressed on small venules
      but only rarely on larger venules. Strong staining for P-selectin on endothelium
      of all large venules was observed in tissues of LPS and TNF-alpha treated animals
      and staining for this newly synthesized P-selectin was enriched at the luminal
      surface of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526956
TI  - Platelet-derived growth factor B-chain-like immunoreactivity in injured rat
      brain.
AB  - Platelet-derived growth factor (PDGF) is a potent mitogen for mesenchymal cells
      and glial cells. For a better understanding of the role of PDGF B-chain in the
      brain, the expression of PDGF B-chain was examined immunohistochemically in
      penetrating injury to the rat brain. Shrunken neurons were distributed with
      enhanced PDGF B-chain-related immunoreactivity (PBRI) in the vicinity of the
      lesion during a period from day 1 to day 4 post injury. Platelet-derived growth
      factor B-chain-related immunoreactivity was transiently observed also in the
      cytoplasm of the numerous brain macrophages in the lesion on day 3 and day 4.
      These distributions of PBRI in the lesion were closely related to the
      neovascularization and astrogliosis there. The close time and spatial correlation
      between the expression of PBRI and cellular responses to injury seen in this
      study suggests PDGF B-chain has an important role in the healing process of
      cerebral wound.

PMID- 7526955
TI  - Integrin-mediated signal transduction in human endothelial cells: analysis of
      tyrosine phosphorylation events.
AB  - Adhesion of human umbilical endothelial cells to fibronectin resulted in
      increased tyrosine phosphorylation of a group of proteins with molecular mass
      ranging from 100 to 130 kDa and of a 70 kDa protein. This pattern of tyrosine
      phosphorylation was also observed when endothelial cells adhered to vitronectin,
      collagen IV, collagen I and laminin or to culture dishes coated with antibodies
      directed to either beta 1, alpha 3, alpha 5, alpha 6 or beta 3 integrin subunits.
      Increased phosphorylation of the 100-130 kDa proteins was detectable as early as
      30 sec after adhesion, reached maximal level after 15 min, and remained high as
      long as the cells adhere to culture dishes. The 70 kDa protein was phosphorylated
      with a slower kinetics and its phosphorylation increased over a period of 3 h.
      Using specific monoclonal antibodies, the major component of the 100-130 kDa
      complex was identified as the focal adhesion tyrosine kinase p125FAK. The
      phosphorylation of the p125FAK was also observed by inducing beta 1 integrin
      clustering in non adherent HEC, indicating that this is a primary signalling
      event induced by integrins. Using tyrosine kinase inhibitors, we show a direct
      correlation between integrin-stimulated tyrosine kinases and assembly of focal
      adhesions and actin fibres.

PMID- 7526957
TI  - Neurochemical predisposition to self-administer cocaine in rats: individual
      differences in dopamine and its metabolites.
AB  - Using in vivo microdialysis, this study attempted to determine whether a
      neurochemical predisposition to self-administer cocaine could be identified.
      Estimated extracellular levels of dopamine and its metabolites were measured
      bilaterally in the mesocorticolimbic and nigrostriatal systems of naive rats that
      were subsequently trained to self-administer cocaine intravenously. There were
      several significant relationships between dopamine and dopamine metabolite (3,4
      dihydroxyphenylacetic acid and homovanillic acid) levels and rates of cocaine
      self-administration during both acquisition and asymptotic phases of testing.
      Dopamine levels in the nucleus accumbens were non-monotonically related to rates
      of self-administration during both phases: low to moderate dopamine levels were
      positively correlated with self-administration rates whereas moderate to high
      dopamine levels were negative correlated with self-administration rates.
      Dopamine, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid)
      levels in the striatum were inversely correlated with self-administration rates
      during the acquisition phase. DOPAC and HVA levels in the left and right sides of
      the medial prefrontal cortex were positively and negatively correlated,
      respectively, with self-administration rates during the asymptotic phase;
      left/right asymmetrics in cortical metabolite levels were also correlated with
      asymptotic rates. There were no significant relationships between any
      neurochemical indices and rates of bar-pressing for water. These results suggest
      that the normal variability in drug seeking behavior is at least in part
      attributable to individual differences in the activity of brain dopamine
      systems.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526958
TI  - Participation of noradrenergic neurotransmission in the suppression by substance
      P of alpha 2-adrenoceptors at the nucleus reticularis gigantocellularis involved
      in central cardiovascular regulation in the rat.
AB  - We applied reverse microdialysis and HPLC analysis to quantify the participation
      of noradrenergic neurotransmission in the modulation by substance P of alpha 2
      adrenoceptors at the nucleus reticularis gigantocellularis involved in
      cardiovascular regulation, using Sprague-Dawley rats anesthetized with
      pentobarbital sodium. The efficacy of circulatory suppression of a centrally
      acting alpha 2-adrenoceptor agonist, guanabenz, was used as the experimental
      index. Continuous infusion of substance P (600 or 1200 pmol/microliters/min) into
      the nucleus reticularis gigantocellularis through a stereotaxically positioned
      microdialysis probe (active exchange length: 500 microns, diameter: 220 microns)
      for 80 min elicited a reduction in the hypotensive and bradycardiac actions of
      guanabenz (100 micrograms/kg, i.v.). This implied suppression of alpha 2
      adrenoceptor activity correlated positively with the time-course of increase in
      the estimated extracellular concentration of the undecapeptide and norepinephrine
      in the nucleus reticularis gigantocellularis. Experimentally elevating the
      concentration of norepinephrine at this reticular nucleus via microinfusion by
      reverse microdialysis also decreased the efficacy of the cardiovascular
      suppression of the aminoguanidine compound. These results suggest that substance
      P may depress the activity of the alpha 2-adrenoceptors in the nucleus
      reticularis gigantocellularis that are involved in central cardiovascular
      regulation via an increase in the extracellular concentration of norepinephrine
      at this reticular nucleus.

PMID- 7526959
TI  - The calcitonin gene-related peptide antagonist CGRP8-37 increases the latency to
      withdrawal responses in rats.
AB  - The present study explored the effects of calcitonin gene-related peptide (CGRP)
      and its antagonist CGRP8-37 on the latency to hindpaw withdrawal responses
      induced by both thermal and mechanical stimulation in rats. (1) Intrathecal
      injection of 10 nmol of CGRP had no effects on the latency to hindpaw withdrawal;
      intrathecal injection of 5 nmol of substance P (SP) decreased the latency to both
      withdrawal responses. (2) Intrathecal administration of 5 nmol or 10 nmol of
      CGRP8-37, but not 1 nmol, induced a significant increase in hindpaw withdrawal
      latency. (3) Intrathecal administration of CGRP8-37 not only reversed the SP
      induced decrease in latency to both withdrawal responses but also mediated a
      significant increase in response latency compared to basal levels. The
      demonstrated results suggest that intrathecal administration of CGRP8-37 has a
      possible antinociceptive effect, and CGRP receptors in the spinal cord may be
      involved.

PMID- 7526960
TI  - Response of cerebral endothelial cells to hypoxia: modification by fructose-1,6
      bisphosphate but not glutamate receptor antagonists.
AB  - Damage to the cerebral endothelium from ischemia could exacerbate brain injury by
      altering vascular integrity, but little is known concerning the response of
      cerebral endothelial cells to hypoxia. To address this issue, cerebral capillary
      endothelial cells were isolated from 14-day-old rats, grown to confluence, and
      placed in hypoxic chambers for up to 62 h. Cells were undamaged by 24 hours of
      hypoxia as assessed by lactate dehydrogenase release and ethidium bromide
      staining, but 48 h resulted in marked damage. Hypoxia was probably exacerbated by
      hypoglycemia because glucose levels fell to < 1 mM by 24 h, at which point ATP
      levels began to fall in hypoxic cultures (3.25 +/- 1.48 nmol/mg protein; mean +/-
      S.D.) relative to normoxic cultures (9.52 +/- 1.41 nmol/mg protein). Cells
      treated with 4 mM fructose-1,6-bisphosphate (FBP) had significantly less damage
      at 48 h of hypoxia than controls. FBP had little effect on rate of glucose
      depletion from the media, but ATP depletion due to hypoxia was significantly
      less. Thus, the protective effect of FBP may be mediated by the ability of
      treated cells to maintain higher ATP levels. Unlike FBP, glutamate receptor
      antagonists including MK-801, NBQX, DNQX, and kynurenic acid were ineffective in
      ameliorating hypoxia-induced endothelial cell injury.

PMID- 7526962
TI  - FMRFamide-like immunoreactivity in presumptive chemosensory afferents of the
      spiny lobster, Panulirus argus.
AB  - Stainings with an antibody against the neuropeptide FMRFamide in the CNS of the
      spiny lobster revealed strong immunoreactivity in a special class of sensory
      afferents. These afferents are extremely thin and numerous and innervate all
      sensory neuropils except the optical and olfactory lobes. In the target neuropils
      the terminals of the afferents branch in parallel and form very densely labeled
      net-like structures. Due to their size, number and distribution we conclude that
      the immunoreactive afferents represent a specialized chemosensory system not
      related to food detection. We propose that a FMRFamide-related peptide present in
      the afferent terminals serves as sensory transmitter.

PMID- 7526961
TI  - The cortico-pallidal projection in the rat: an anterograde tracing study with
      biotinylated dextran amine.
AB  - The projections from the frontal cortex to the pallidum (e.g. the globus pallidus
      and the entopeduncular nucleus) were studied in the rat using the biotinylated
      dextran amine (BDA) anterograde tracing method. Injections of BDA into the
      precentral medial and precentral lateral cortices consistently yielded labeling
      of thin fibers with small boutons in the ipsilateral pallidum although not in the
      contralateral pallidum. Electron microscopic observation revealed that BDA
      labeled boutons form asymmetric synapses mainly with small dendrites and
      dendritic spines. When the injection sites included the insular, orbital, and
      prelimbic cortices, the labeled fibers and boutons were also seen in the ventral
      pallidum, the basal nucleus of Meynert, and the substantia innominata. Injections
      of BDA in the parietal and occipital cortices resulted in either very few
      labeling or no labeled boutons in the pallidum. The cortico-pallidal projections
      were topographically organized. The density of labeled boutons in the globus
      pallidus was found to be approximately 10% of the density of cortical terminals
      in the neostriatum.

PMID- 7526963
TI  - Olivary projecting neurons in the nucleus of Darkschewitsch in the cat receive
      excitatory monosynaptic input from the cerebellar nuclei.
AB  - The direct projection from the cerebellar nuclei to the inferior olive is
      GABAergic. In the present study, we investigated the projection from the
      cerebellar nuclei to the mesodiencephalic junction which is known to provide an
      excitatory projection to the inferior olive. The mesodiencephalic junction was
      studied in cat following anterograde transport of wheatgerm agglutinated
      horseradish peroxidase from the cerebellar nuclei in combination with: (1)
      retrograde transport of gold-lectin conjugate from the inferior olive; and (2)
      postembedding GABA-immunocytochemistry. Light microscopic analysis revealed that
      overlap of the anterograde and retrograde labeling was especially prominent in
      the nucleus of Darkschewitsch. Electron microscopic examination of this area
      showed: (1) that many cerebellar terminals made synaptic contacts with neurons
      that project to the inferior olive; (2) that virtually all cerebellar terminals
      were non-GABAergic and displayed an excitatory morphology; and (3) olivary
      projecting neurons were non-GABAergic. It is concluded that the indirect
      cerebellar projection to the inferior olive via the nucleus of Darkschewitsch is
      disynaptic and excitatory.

PMID- 7526964
TI  - Multiple types of nitrogen monoxide synthase-/NADPH diaphorase-containing neurons
      in the human cerebral neocortex.
AB  - Nitrogen monoxide (NO) synthase (NOS)-containing neurons (NOSN) were identified
      by means of reduced nicotinamide adenine dinucleotide phosphate (NADPH)
      diaphorase histochemistry in nine areas of the human cerebral neocortex from
      patients 9-74 years of age. Labeled neurons were analyzed according to their
      disposition in the various layers of the cortical gray and immediately subjacent
      white matter, and classified according to their cytological features. The vast
      majority of NOSN (about 80%) are situated in the subcortical white matter and not
      in the cortical gray proper. Nevertheless, these NOSN extend their processes into
      the cortical gray and thus appear to participate in intracortical circuits, along
      with the minority of NOSN situated in all cortical layers. Although many NOSN are
      small aspiny local circuit neurons, as reported previously, additional distinct
      cytological types of NADPH diaphorase-positive neurons were also identified,
      including: (a) local circuit neurons in layer I; (b) granule cells in layer II,
      and (c) non-pyramidal neurons with densely spinous dendrites in the white matter
      immediately under the cortical gray. Processes fulfilling light microscopic
      criteria for axons were seen in many of the above cell types originating from
      proximal dendrites and, less frequently, from a presumed axon hillock. Taken
      together, these observations indicate that NOSN belong to several distinct
      morphological and presumably functional classes, some of which have a unique or
      restricted laminar location, raising the possibility that some of these various
      classes of neurons may be selectively affected or spared in neurodegenerative
      disorders.

PMID- 7526965
TI  - Photic induction of Fos immunoreactivity in the suprachiasmatic nuclei of the
      blind mole rat (Spalax ehrenbergi).
AB  - Exposure to light during the dark phase entrains c-fos expression in cells of the
      suprachiasmatic nuclei in the blind mole rat (Spalax ehrenbergi). Labeled cells
      are mainly located in the ventral region of the nucleus where retinal afferents
      terminate. Despite severe atrophy of the eye and regression of thalamic and
      tectal structures, the retinal pathways and central mechanisms involved in
      photoperiodic perception and circadian regulation appear to be similar to those
      in other rodents.

PMID- 7526966
TI  - Upregulation of neuronal nitric oxide synthase and mRNA, and selective sparing of
      nitric oxide synthase-containing neurons after focal cerebral ischemia in rat.
AB  - Nitric oxide synthase-containing neurons are presumed to be resistant to
      neurodegeneration and neurotoxicity, however this resistance has not been
      demonstrated after focal cerebral ischemia. We therefore measured the temporal
      profile of neuronal nitric oxide synthase (NOS-I) mRNA and immunoreactivity and
      NADPH-diaphorase reactivity over a one week period after permanent middle
      cerebral artery (MCA) occlusion in 48 male Wistar rats and compared these data to
      ischemic cell damage as evaluated on hematoxylin and eosin (H & E) stained
      sections by light microscopy. NOS-I mRNA increased as early as 15 min after MCA
      occlusion in the ipsilateral striatum and maximal expression of NOS-I was found
      in the ipsilateral cortex and striatum 1 h after MCA occlusion. The numbers of
      NOS-I-containing neurons in the ipsilateral cortex and striatum were
      significantly greater (P < 0.05) than NOS-I-containing neurons in the
      contralateral hemisphere at 2-48 h after the onset of ischemia. The number of NOS
      I-containing neurons peaked at 4 h after MCA occlusion. Neurons exhibited
      shrinkage or were swollen at 1 to 4 h after MCA occlusion. At 24-48 h after
      ischemia, neurons in the ischemic lesion appeared to be eosinophilic or ghost
      like on H & E stained sections. However, some of these neurons retained
      morphological integrity on the NOS-I immunohistochemical sections. At 168 h after
      ischemia, all neurons within the lesion appeared necrotic on H & E stained
      sections; however, scatterred neurons expressed NOS-I and NADPH-diaphorase. The
      rapid upregulation of NOS-I and mRNA in the ischemic lesion suggests that NOS-I
      is involved in focal cerebral ischemic injury; the expression of NOS-I by neurons
      that retain their morphological structure in the area of the infarct suggests
      that NOS-I-containing neurons are more resistant to the ischemic insult. Our data
      also indicate a close association of NOS-I immunoreactivity and NADPH-diaphorase
      reactivity in ischemic brain.

PMID- 7526967
TI  - A major continuous allergenic epitope of bovine beta-lactoglobulin recognized by
      human IgE binding.
AB  - Hexapeptides of sequential overlapping sequences of beta-lactoglobulin (BLG) were
      used to probe serum from children with immediate-type cow milk allergy for IgE
      binding to continuous epitopes of BLG in an enhanced enzyme-linked immunosorbent
      assay (ELISA). Six regions of IgE binding were identified on the BLG molecule and
      these were synthesized as dodecapeptides. Inhibition of IgE binding to whole BLG
      was used to confirm the BLG-specific binding of IgE to each of the synthesized
      peptides. One of the peptides, peptide 4, showed inhibition in an IgE anti-BLG
      radioimmunoassay to all 16 sera tested. The patterns of inhibition with the
      native BLG molecule and peptide 4 were significantly correlated (P = 0.005),
      suggesting that this peptide contains a major continuous IgE binding epitope of
      BLG.

PMID- 7526968
TI  - Nucleolar organizer regions in adenocarcinoma of the uterine cervix.
AB  - BACKGROUND: Nucleolar organizer regions (AgNORs) are associated with
      proliferative activity and ploidy in many tumors. The endocervical growth pattern
      of cervical adenocarcinoma renders tumor volume assessment more difficult,
      necessitating additional prognostic indicators. METHODS: Thirty-five cases of
      cervical adenocarcinoma were evaluated by reviewing charts and histologic
      sections. Nucleolar organizer regions were stained and counted manually; the mean
      number per cell and the percentage of cells with more than 5 AgNORs were
      recorded. Ploidy and S-phase fraction were determined by flow cytometry. RESULTS:
      Mean AgNOR counts per cell were significantly higher in adenocarcinoma (3.0) and
      adenosquamous carcinoma (4.3) than in benign endocervical epithelium (1.4). Grade
      3 tumors had higher values (4.0) than Grade 1 lesions (2.9), and tumors with
      lymphovascular space involvement had higher values (3.5) than tumors without such
      involvement (2.7). No significant correlation was seen with regard to tumor stage
      or size. Flow cytometric parameters did not correlate with any of the examined
      parameters, although the DNA index was higher in larger tumors. Correlation
      between AgNOR counts and flow cytometry was significant only in Grade I tumors.
      CONCLUSIONS: Nucleolar organizer region counts correlated better with histologic
      parameters of cervical adenocarcinoma than did flow cytometry. Because it is
      easily performed and does not require sophisticated equipment, AgNOR counts
      should be investigated further in a larger group of patients to determine their
      prognostic value.

PMID- 7526969
TI  - Cost-effective prostate cancer detection. Reduction of low-yield biopsies.
      Investigators of the American Cancer Society National Prostate Cancer Detection
      Project.
AB  - BACKGROUND: In hopes of limiting low-yield prostate biopsies, results of digital
      rectal examination (DRE), transrectal ultrasound (TRUS), prostate specific
      antigen (PSA) and age-related PSA values, gland-volume-adjusted PSA levels, and
      longitudinal PSA changes were analyzed to identify their cost-effectiveness as
      prognostic indicators in screening, biopsy, and follow-up of patients with
      prostate cancer. METHODS: Twenty-nine hundred men with complete data sets from an
      initial cohort of 2999 men with an annual follow-up for up to 5 years were
      examined. Intrapatient PSA and gland-volume variability, optimal PSA operating
      points (o.p.), and test performance scores were determined for each parameter.
      Decision analysis was then applied retrospectively to each parameter to determine
      the cancer detection yield, biopsy requirements, and costs for commonly used
      detection strategies. RESULTS: For the initial screening decision, the optimal
      PSA o.p. was 3.0 ng/ml but increased to 5.0 ng/ml in combination with DRE,
      whereas age-related PSA performed no better than did PSA. The mean intrapatient
      variability in TRUS gland volume (+5.5 cc) relative to mean volume (34 cc) was
      16%, which was less than the 28% (0.64/2.3 ng/ml) relative variability for PSA.
      For biopsy decisions, using PSA density (PSAD) with a level of 0.12 ng/ml/cc
      there was no significant difference in accuracy compared with the systematic
      biopsy of all patients with elevated PSA or age-related PSA levels. Rather than
      perform systematic biopsy on all patients with PSA levels greater than 4 ng/ml,
      decision analysis showed that a 16-55% reduction in biopsies could be achieved
      with a respective cancer loss of 4-25% by limiting biopsy to patients with an
      increased PSAD level and/or abnormal results of DRE. Using age-related PSA
      criteria in combination with DRE reduced biopsies by 12% but resulted in minimal
      cost reductions. The greatest biopsy reduction relative to cancer yield and
      lowest cost per cancer detected occurred with PSAD-driven biopsy strategies.
      During follow-up, longitudinal changes in absolute PSA and PSAD levels were
      significantly better (P < 0.05) than the percentage change in PSA levels per
      year. CONCLUSIONS: Cost-effective prostate cancer detection with PSA as a
      parameter is better achieved if screening and biopsy decisions are not linked
      intimately. A tailored-biopsy approach for patients with disproportionately
      elevated PSA levels of suspicious DRE results in the greatest biopsy reduction by
      selecting lower risk groups for more conservative follow-up.

PMID- 7526970
TI  - Morphologic and immunohistochemical changes in prostate cancer after preoperative
      hormonal therapy. A comparative study of radical prostatectomies.
AB  - BACKGROUND: Estramustine phosphate (EMP) and flutamide (FL) were used as
      reversible preoperative hormonal drugs in the surgical treatment of patients with
      localized prostate cancer. METHODS: The authors descriptive and quantitatively
      examined the morphologic and immunohistochemical changes in 40 of 200 step
      sectioned radical prostatectomies, obtained after treatment with EMP (25
      patients) and with FL (15 patients). Of these, 28 pretreatment needlecore
      biopsies were available. RESULTS: Every specimen contained adenocarcinoma.
      Understaging was found in 50% of the cases and a higher Gleason score in 70%.
      Benign glands underwent atrophy and squamous metaplasia. Treated tumors showed
      cytoplasmic vacuolization, nuclear pyknosis, fibrosis and lymphocytic
      infiltrates. The EMP group had an 84% (P < 0.05) higher mean total regression
      score than the FL group. Estramustine phosphate induced a 56% (P < 0.05) and a
      34% decrease in tumoral prostate specific antigen and prostate specific acid
      phosphatase intensity scores, respectively, versus 29% and 32% after FL. The mean
      proliferating cell nuclear antigen (PCNA) labeling index and the mean mitotic
      index of the EMP group were 52% (P < 0.05) and 70% (P < 0.05) lower than those
      measured in the FL group. Each FL-treated tumor and 92% of EMP-treated tumors
      expressed chromogranin A (ChrA); ChrA labeling correlated significantly with PCNA
      labeling. Seventy-six percent of EMP-treated specimens revealed venous
      thrombosis. CONCLUSIONS: Estramustine phosphate induces important morphologic and
      immunohistochemical changes in prostate cancer with an apparent decrease of
      secretory and proliferative activity when compared with FL-treated tumors. These
      changes represent pitfalls in the diagnosis and grading of treated carcinomas.
      Nearly every treated adenocarcinoma of the prostate has neuroendocrine
      differentiation, showing increasing ChrA labeling with higher tumor stage. A
      significant correlation between tumor proliferation and neuroendocrine
      differentiation was noticed in this small cohort of patients. There was a high
      incidence of periprostatic venous thrombosis after EMP treatment.

PMID- 7526971
TI  - Relationship of DNA ploidy to histology and prognosis in rhabdomyosarcoma.
      Comparison of flow cytometry and image analysis.
AB  - BACKGROUND: Although DNA ploidy correlates with prognosis in certain childhood
      cancers, e.g., neuroblastoma, its significance in rhabdomyosarcoma (RMS) is
      unclear and controversial. METHODS: Ploidy by flow cytometry (FCM) and image
      analysis (IA) in 26 of 27 children with RMS (17 embryonal, 3 mixed
      embryonal/alveolar, 5 alveolar, 1 anaplastic, 1 ectomesenchymoma) and 4 adults
      with pleomorphic RMS were evaluated. Statistical comparisons were analyzed
      between DNA content and gender, age, localization, Intergroup Rhabdomyosarcoma
      Study (IRS) group, and histopathologic subtype. Survival analyses were performed
      by the Kaplan-Meier test using the approximate chi-square statistic for the log
      rank test. RESULTS: The concordance rate between FCM and IA was 26 of 30 (87%);
      FCM was not performed in one tumor. Image analysis was more sensitive than FCM in
      detecting aneuploidy. Furthermore, DNA content was associated significantly with
      histologic subtype (P = 0.031); embryonal histology commonly was hyperdiploid
      (mean, 1.44; median, 1.27), whereas alveolar histology usually was near
      tetraploid (mean, 1.83; median, 1.95). All four adult patients with pleomorphic
      RMS were aneuploid, with one showing multiple DNA peaks. No correlation between
      DNA content and survival was observed in the children with RMS. However, IRS
      group (P = 0.011) and patient age (P = 0.036) were independent prognostic
      indicators significantly related to survival. All adult patients died of their
      disease. CONCLUSIONS: Although ploidy correlates with histologic subtype, DNA
      content is not significantly predictive of prognosis in patients with RMS. Age at
      diagnosis and IRS group are independent predictors of clinical outcome in
      children with RMS.

PMID- 7526974
TI  - Mutagen sensitivity as a marker of cancer risk.
AB  - There are measurable differences, genetically determined, in susceptibility to
      carcinogenic activity. Variation in metabolism of xenobiotic chemicals is one
      determinant of susceptibility and is attributed to polymorphisms in a number of
      enzymes. There may also be a wide spectrum of DNA-repair capability within the
      population. A peripheral lymphocyte assay has been developed in which in vitro
      bleomycin-induced chromosome breaks provides an indirect measurement of such
      repair. Mutagen sensitivity as defined by this assay has been shown to be an
      independent risk factor for tobacco-related malignancies, especially those of the
      upper aerodigestive tract. Preliminary data also suggest familial aggregation of
      cancer in mutagen-sensitive patients. Risk assessment is now recognized as a
      multidisciplinary process, extending beyond the scope of traditional
      epidemiologic methodology to include biological evaluation of interindividual
      differences in carcinogenic susceptibility. These susceptibility markers will
      enable us to identify high-risk population subgroups that can be targeted for
      intensive primary and secondary preventive strategies.

PMID- 7526973
TI  - Synthesis of carboxyl-reduced analogues related to the Chlamydia-specific Kdo
      trisaccharide epitope.
AB  - The disaccharides allyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)
      (2-->4)-3-deoxy-a lph a-D- manno-2-octulopyranoside (8), allyl O-(3-deoxy-alpha-D
      manno-2-octulopyranosyl)-(2-->8)-(sodium 3-deoxy-alpha-D-manno-2
      octulopyranosidonate) (24), and allyl O-(sodium 3-deoxy-alpha-D-manno-2
      octulopyranosylonate)-(2-->8)-3-deoxy-a lph a-D- manno-2-octulopyranoside (35),
      and the trisaccharides allyl O-(sodium 3-deoxy-alpha-D-manno-2
      octulopyranosylonate)-(2-->8)-(sodium 3-deoxy-alpha-D-manno-2
      octulopyranosylonate)-(2-->4)-3-deoxy-a lph a-D-manno-2-octulopyranoside (13) and
      allyl O-(3-deoxy-alpha-D-manno-2-octulopyranosyl)-(2-->8)-(sodium 3-deoxy-alpha-D
      manno-2-octulopyranosylonate)-(2-->4)-(sodium 3-deoxy-alpha-D-manno-2
      octulopyranosidonate) (30) were prepared. The ketosidic linkages were formed in
      good yields and high stereoselectivity by BF3 . Et2O-catalyzed reaction of the
      per-O-acetylated 3-deoxy-alpha-D-manno-2-octulopyranosyl fluoride derivative (16)
      with 8-O-SiButMe2 derivatives 19 and 21. Coupling reactions using the Kdo
      monosaccharide bromide derivative 4 or the alpha-(2-->8)-linked Kdo disaccharide
      bromide derivatives 9 and 26 were performed under Helferich conditions in MeCN or
      MeNO2, respectively. The disaccharide halides were prepared in good overall
      yields starting from the readily available allyl beta-glycoside of Kdo. The
      deprotected oligosaccharides correspond to the genus-specific lipopolysaccharide
      epitope of Chlamydia and part structures thereof, containing the carboxyl-reduced
      Kdo-residues at the distal and proximal position of the Kdo trisaccharide
      epitope, respectively.

PMID- 7526975
TI  - [Extrasystolic ventricular bigeminy in ventricular tachycardia].
AB  - A patient with recent myocardial infarction presented with premature ventricular
      contractions (PVCs), couplets, and runs of ventricular tachycardia (VT). Two
      types of ectopic complexes, labeled A and B, were present. Isolated PVCs, as well
      as the first complex in a couplet, were always type A beats. In contrast, the
      second beat in a couplet was always a type B beat. Any run of VT was initiated by
      a type A beat. Monomorphic VT was made only of type B complexes, apart from the
      first one. Several episodes of VT, however, reflected an alternation of type A
      and type B complexes with alternating cycle length. This is a manifestation of
      extrasystolic ventricular bigeminy where any VT impulse (type B) is followed by
      an extrasystole (type A). In addition, extrasystolic impulses affect the
      tachycardia, resetting its cycle.

PMID- 7526972
TI  - RNA expression of complement regulatory proteins in human brain tumors.
AB  - The expression of complement regulatory proteins (CRP) on the surface of
      neoplastic cells has been proposed as a mechanism by which these cells evade
      immune surveillance. We have examined the RNA expression of the genes that encode
      5 kinds of CRP in various human brain tumors to determine whether CRP expression
      might play a role in the malignant progression of these tumors. The benign and
      atypical meningiomas, and the astrocytomas showed high expression of SP-40,40,
      low expression of CD59, and barely detectable expression of CD46, CD55 and S
      protein. The benign and atypical menigiomas showed significantly greater
      expression of SP-40,40 at the RNA level when compared to malignant meningiomas.
      This study describes the mRNA expression of meningiomas, astrocytomas, tumor cell
      lines and normal human tissues.

PMID- 7526977
TI  - The history of public health and the modern state. Introduction.

PMID- 7526976
TI  - Modulation of pyrogen-induced upregulation of endothelial cell adhesion molecules
      (CAMs) by interleukin-4: transcriptional mechanisms and CAM-shedding.
AB  - The pyrogens interleukin 1 (IL-1), tumor necrosis factor (TNF), and bacterial
      lipopolysaccharides (LPS) are known to increase endothelial cell (EC)
      adhesiveness for leukocytes by stimulating surface expression of various adhesion
      molecules. IL-4, a product of activated T-cells, was shown to affect pyrogen
      mediated regulation of EC adhesion molecule surface expression. In the present
      study, we investigated the effect of IL-4 on pyrogen-induced upregulation of the
      cell adhesion molecules (CAMs) ICAM-1 (intercellular cell adhesion molecule-1),
      ELAM-1 (endothelial leucocyte adhesion molecule-1), and VCAM-1 (vascular cell
      adhesion molecule-1) in cultured human umbilical vein EC (HUVEC). Surface
      expression of adhesion molecules was quantified by flow cytometry, HUVEC mRNA
      content was estimated by Northern blot analysis, and ICAM-1 antigen in
      conditioned media was measured by ELISA. Incubation of HUVEC with IL-1 (100
      U/ml), TNF (500 U/ml), and LPS (10 micrograms/ml) caused significant increase in
      ICAM-1, ELAM-1, and VCAM-1 surface expression; IL-1 caused about an eightfold
      increase in ICAM-1 expression, about a 13-fold increase in ELAM-1 surface
      expression, and about a fourfold increase in VCAM-1 expression. Coincubation of
      pyrogens with IL-4 (500 U/ml) differentially influenced their proadhesive effects
      on the HUVEC surface. In the presence of IL-4, IL-1-induced ICAM-1 upregulation
      was reduced, ELAM-1 upregulation was not significantly influenced by IL-4, and
      induction of VCAM-1 was enhanced by IL-4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526979
TI  - State medicine in Great Britain.

PMID- 7526980
TI  - The people's health: public health policies in Sweden.

PMID- 7526978
TI  - Public health in Germany.

PMID- 7526981
TI  - The expert and the state in Russian public health: continuities and changes
      across the revolutionary divide.

PMID- 7526982
TI  - Public health and the state: the United States.

PMID- 7526983
TI  - Public health in Canada.

PMID- 7526986
TI  - Public health in colonial Africa: the Belgian Congo.

PMID- 7526987
TI  - Public health in modern Japan: from regimen to hygiene.

PMID- 7526985
TI  - Crisis and contradiction in India's public health.

PMID- 7526988
TI  - Internationalism in medicine and public health.

PMID- 7526984
TI  - A New World? Two hundred years of public health in Australia and New Zealand.

PMID- 7526989
TI  - Public health in France.

PMID- 7526991
TI  - Sulfated polysaccharides are required for collagen-induced vascular tube
      formation.
AB  - We have previously shown that soluble type I collagen can induce vascular tube
      formation when it contacts the apical side of a confluent endothelial monolayer.
      In this study we have examined which soluble agent(s) are required for collagen
      induced tube formation. Human neonatal foreskin microvascular endothelial cells,
      maintained in basal medium, were preincubated with each test agent for 2 h prior
      to the addition of solubilised type I collagen (100 micrograms/ml). After 6 h,
      tube formation was quantitated using image analysis and expressed as the mean
      area of tube formation (mm2) per microscopic field of view. Collagen-induced tube
      formation did not occur in the presence of endothelial cells growth supplement,
      basic fibroblast growth factor, or normal pooled human serum. In contrast, the
      addition of heparin at 5 or 50 micrograms/ml caused extensive tube formation
      (0.22 +/- 0.07 and 0.30 +/- 0.12 mm2, respectively) whereas at 500 micrograms/ml
      little tube formation occurred (0.03 +/- 0.02 mm2). Protamine sulfate, an
      antagonist of heparin, inhibited collagen-induced tube formation in a dose
      dependent manner. Pentosan polysulfate, dextran sulfate, heparan sulfate, and
      chondroitin sulfate mimicked the action of heparin. Partially sulfated heparin
      (de-N-sulfated heparin) stimulated less tube formation compared to heparin (0.15
      +/- 0.06 mm2 at 50 micrograms/ml). The nonsulfated polysaccharides, xylan and
      dextran, had no effect on tube formation. In summary, sulfated polysaccharides
      are required for collagen-induced vascular tube formation in vitro. The sulfation
      of these molecules appears to be vital for collagen-induced tube formation.

PMID- 7526993
TI  - Induction of endothelial cell differentiation in vitro by fibroblast-derived
      soluble factors.
AB  - Recent studies have suggested that fibroblasts, widely distributed mesenchymal
      cells, not only function to sustain various organs and tissues as stroma cells
      but also act directly to regulate adjacent cell behavior including migration,
      proliferation, and differentiation. Since fibroproliferative diseases and lesions
      (fibroplasia) are accompanied by new capillary growth (angiogenesis), we
      hypothesized that fibroblasts may have direct effects on endothelial cell
      behavior, independent of the elaboration of extracellular matrix, that are
      relevant to complex process of angiogenesis. To test this hypothesis, bovine
      aortic endothelial cells were cocultured in collagen gels with human skin
      fibroblasts. This coculture system caused the endothelial cells to become spindle
      shaped and to organize into a capillary-like structure within the collagen gels.
      We found that fibroblast-conditioned medium (FCM) also induced endothelial cells
      initially to elongate and subsequently to organize into a capillary-like
      structure within collagen gels. While FCM had no significant effect on
      endothelial cell DNA synthesis, the soluble factor(s) in FCM increased
      endothelial cell motility in an in vitro wound assay and in a Boyden chamber
      assay. The chemoattractant(s) in FCM was alkaline (pH 9.0)--and acid (pH 3.0)-
      stable, relatively heat stable (stable at 60 degrees for 30 min, unstable at 98
      degrees C for 3 min), dithiothreitol (DTT)-sensitive, and bound to an anionic
      exchange resin (DEAE-cellulose). Another factor(s) stimulated endothelial cell
      reorganization into capillary-like structure both within a collagen gel and on a
      reconstituted basement membrane matrix, Matrigel. This factor(s) was alkaline (pH
      9.0)- and acid (pH 3.0)--stable, heat (98 degrees C for 3 min)-stable, and DTT
      sensitive and bound an anionic exchange resin (DEAE-cellulose). These in vitro
      results suggest that fibroblasts secrete soluble factors that can influence
      endothelial cell behaviors relevant to the angiogenesis process with possible
      implications for vascularization in fibroproliferative conditions.

PMID- 7526990
TI  - Enhanced chiral separation of dansylated amino acids with cyclodextrin-dextran
      polymer network by capillary electrophoresis.
AB  - A method for the chiral separation of dansyl-DL-amino acid mixtures using a
      dextran (M(r) 2,000,000) polymer network containing beta-cyclodextrin (beta-CD)
      in HPCE was developed. Mixtures of up to seven amino acids could be baseline
      resolved by this method under neutral pH conditions. Resolution was dependent on
      the dextran concentration in the polymer network. Temperature effects on the
      chiral separation were studied. Optimal efficiency and resolution of DL
      enantiomeric pairs of amino acid samples were obtained at 25 degrees C. The
      resolution of different amino acids used in this work decreased with an increase
      in temperature.

PMID- 7526992
TI  - Primary cultures of normal and tumoral human ovarian epithelium: a powerful tool
      for basic molecular studies.
AB  - To begin delineating the cellular and molecular events that are important in
      ovarian carcinogenesis, we have developed a simple and rapid method for the
      establishment of primary cultures derived from benign tumors, malignant tumors,
      and ascites of the ovary that are representative of the original clinical
      material from which they are derived. From 23 ovarian epithelial ascites
      collected, 13 were successfully established in culture and cells survived an
      average of 7 to 8 passages. From 65 solid epithelial ovarian tumors (benign and
      malignant) 36 were cultured for an average of 6 passages for cultures derived
      from benign tumors and 11 or 12 passages in the case of malignant tumors. Cells
      were scored as epithelial in nature by morphology and histochemical analysis
      using anti-cytokeratin antibodies. Cultures, especially those derived from solid
      tumors, sometimes displayed fibroblastic-like contamination which was quickly
      resolved. We include limited molecular analyses both to characterize the origin
      of the populations we have established as well as to demonstrate the usefulness
      of these cultures in molecular studies.

PMID- 7526994
TI  - Assembly dynamics of epidermal keratins K1 and K10 in transfected cells.
AB  - Keratins K1 and K10 are early markers of keratinization. Their expression starts
      when basal keratinocytes are committed to differentiate. To study keratin
      stability and intermediate filament (IF) assembly and dynamics, we have forced
      the expression of K1/K10 in epithelial and nonepithelial cell lines. It was
      observed that these keratins are unable to generate a normal cytoskeleton in
      fibroblasts, where they form, at most, abnormally short and twisted filaments.
      However, when transfected into epithelial cells they frequently cointegrate with
      the endogenous keratin into a well-developed cytoskeleton. These results suggest
      that the K1/K10 pair is unable to form a keratin network on its own and that,
      mimicking the in vivo situation, requires a preexisting cytoskeleton. Besides,
      filaments, transfected K1/K10 also form fairly stable, regularly sized round
      aggregates with no evidence of organization into IF. Transfections with single
      genes demonstrated that these structures were generated by K10 alone. These
      aggregates interacted with most components of the cellular cytoskeleton, altering
      the distribution of the endogenous keratins, actin, vimentin, and tubulin.
      Kinetic experiments in transfected PtK2 cells showed that, contrary to
      expectations, K10 does not integrate directly into the preexisting cytoskeleton,
      but assembles into the stable nonfilamentous aggregates. From these structures,
      K10 evolves toward the formation of IF together with the endogenous keratins
      through a complex and highly dynamic process, which involves substantial
      rearrangement of the endogenous keratin cytoskeleton. These results demonstrate
      that K1 and K10 have properties different from those described for other keratins
      and that epithelial IF are surprisingly dynamic structures.

PMID- 7526995
TI  - Fas-mediated apoptosis in primary cultured mouse hepatocytes.
AB  - The Fas antigen is a member of the tumor necrosis factor/nerve growth factor
      receptor family and is expressed in tissues such as the thymus, liver, and ovary.
      Agonistic anti-Fas antibodies have cytolytic activity against cell lines
      expressing the Fas antigen. In this study, we show that anti-Fas antibody can
      induce the death of mouse hepatocytes in primary culture. Cell death via
      apoptosis was evidenced by the fact that the dying cells displayed DNA
      fragmentation, extensive surface bleb formation, and chromatin condensation. Anti
      Fas antibody alone induced apoptosis in less than 20% of the cultured
      hepatocytes, whereas all cells were killed within 24 h by anti-Fas antibody in
      the presence of actinomycin D, cycloheximide, or protein kinase C (PKC)
      inhibitors such as H-7 and HA1004. These results indicate that the Fas antigen
      expressed in mouse hepatocytes functionally transduces the apoptotic signal and
      suggest that cultured mouse hepatocytes express protective proteins against
      apoptosis and that phosphorylation by PKC is also involved in protection of the
      hepatocytes from Fas-mediated apoptosis.

PMID- 7526996
TI  - Platelet-derived growth factor-BB stimulates synthesis of the integrin alpha 2
      subunit in human diploid fibroblasts.
AB  - Platelet-derived growth factor (PDGF)-BB stimulates fibroblast-mediated
      contraction of collagen gels, as well as migration of fibroblasts through
      collagen-coated membranes. In the present study we examined effects of PDGF-BB
      stimulation on the synthesis of collagen-binding beta 1 integrins by human
      diploid fibroblasts (AG 1518). PDGF-BB stimulation led to an increase in the rare
      of integrin alpha 2-subunit synthesis. In contrast, synthesis of the integrin
      alpha 1- or alpha 3-subunits were not affected by PDGF-BB stimulation.
      Furthermore, levels of alpha 2-subunit mRNA relative to levels of glyceraldehyde
      3-phosphate dehydrogenase (GAPDH) mRNA increased after PDGF-BB stimulation. The
      latter finding is compatible with PDGF-BB stimulating transcription of the alpha
      2-subunit gene. PDGF-BB stimulation did not influence the relation between levels
      of integrin beta 1-subunit mRNA and GAPDH mRNA. In addition, the rate of
      synthesis or post-translational processing of the integrin beta 1-subunit were
      not, or only marginally, affected by PDGF-BB stimulation. It is likely that the
      motility response elicited in fibroblasts by PDGF-BB involves such alterations in
      the synthesis of the alpha 2-subunit of the alpha 2 beta 1 collagen-binding
      integrin.

PMID- 7526997
TI  - "Proliferative keratin cyst," a lesion in the lungs of rats following chronic
      exposure to para-aramid fibrils.
AB  - Cystic and keratinizing squamous lesions have been observed in rats exposed
      chronically to a number of particulates. A variety of diagnostic terms have been
      applied to these pulmonary lesions but no consensus exists as to their most
      proper morphological classification. In an attempt to obtain a consensus for
      cystic keratinizing pulmonary lesions produced in rats by Kevlar para-aramid
      fibrils and TiO2 powder, a panel of medical and veterinary pathologists was
      invited to participate in a workshop addressing the morphology of the lesions and
      to reach a consensus on a suitable descriptive diagnostic term. All participants
      agreed that the cystic keratinizing lesions were not malignant neoplasms. The
      majority was of the opinion that the lesions were not neoplasms. A minority
      (3/13) considered the lesions to be benign tumors. The panel considered that the
      most appropriate morphologic diagnosis for the lesions was "proliferative keratin
      cyst" (PKC). In addition, the panel agreed on the following descriptive text:
      "The lesions are cysts lined by a well-differentiated stratified squamous
      epithelium with a central keratin mass. Growth appears to have occurred by
      keratin accumulation and by peripheral extension of the metaplastic change into
      the adjacent alveolar spaces. The lesions are sharply demarcated except in those
      areas in which there has been extension of metaplasia into adjacent alveoli. The
      squamous epithelium has few mitotic figures and dysplasia is absent."

PMID- 7526999
TI  - Significance of IgG and IgM HCV antibody secretion in vitro in patients with
      chronic hepatitis C: correlation with disease activity and response to interferon
      alpha.
AB  - Hepatitis C virus antibodies are found in the serum of most patients with chronic
      hepatitis C. However, the significance of the humoral response is still
      uncertain. In this study, in vitro IgG and IgM anti-hepatitis C virus secretion
      by peripheral blood mononuclear cells of patients with chronic hepatitis C was
      analyzed. Peripheral-blood mononuclear cells from 21 of 36 patients (58.3%)
      secreted IgG anti-hepatitis C virus in vitro, as demonstrated with anti-hepatitis
      C virus-specific enzyme immunoassays and recombinant immunoblot assays. Ten of
      the 36 patients (27.8%) showed both IgG and IgM anti-hepatitis C virus core in
      vitro. In 9 of these 10 patients, IgM anti-hepatitis C virus was also detected in
      serum. Patients with in vitro IgM or IgG anti-hepatitis C virus secretion had
      higher ALT levels in serum than did patients without such secretion in vitro
      (99.5 +/- 22.1 and 85.6 +/- 34.4 vs. 38.1 +/- 37.4 U/L; p < 0.0001, p < 0.001).
      Furthermore, with a histology activity score it was demonstrated that patients
      with in vitro IgM or IgG HCV antibodies (or both) had more severe chronic active
      hepatitis than did patients without in vitro hepatitis C virus antibody secretion
      (p < 0.01). To analyze the therapy outcome, we included in this study 18 patients
      who had received interferon-alpha previously. Seven of eight in vitro hepatitis C
      virus antibody-positive patients were nonresponders, whereas the in vitro
      hepatitis C virus antibody-negative patients were mostly complete therapy
      responders (8 of 10).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527000
TI  - Prednisone-interferon combination in the treatment of chronic hepatitis B: direct
      and indirect metanalysis.
AB  - The aim of this study was to review all published randomized clinical trials
      evaluating the efficacy of a combination of prednisone and interferon in
      treatment of chronic hepatitis B and to subject these studies to metanalysis. Two
      types of metanalyses were carried out: direct metanalysis, comparing the
      prednisone-interferon combination with interferon on its own; and indirect
      metanalysis, comparing the treatment efficacy of prednisone-interferon and of
      interferon with control results. At the end of follow-up, four assessable end
      points were analyzed: HBeAg, hepatitis B virus DNA, HBsAg loss and serum ALT
      normalization rate. The direct metanalysis included seven trials comparing
      prednisone-interferon with interferon treatment. No significant differences were
      observed between the two types of therapy, for all the criteria given. However,
      in patients with low ALT levels, the prednisone-interferon combination gave
      significantly better results than interferon alone--HBeAg loss was 48% in the
      former group vs. 18.4% with interferon alone (p < 0.01). Fifteen trials compared
      interferon with control values; all end points were significantly improved. Seven
      trials compared prednisone-interferon with control results and showed all end
      points to be significantly improved by treatment. Indirect metanalysis showed
      that the differences in odds ratios for prednisone-interferon/control group and
      interferon/control group studies were negative for all assessable end points. In
      conclusion, the use of corticosteroids did not produce any significant increase
      in the efficacy of interferon treatment in adults with chronic hepatitis B and
      high initial ALT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7526998
TI  - Inhibition of lymphocyte-induced angiogenesis by free radical scavengers.
AB  - Solid tumors induce an angiogenic response by the host blood vessels to form a
      new vascular network for the supply of fresh nutrients and oxygen responsible for
      tumor growth. Furthermore, tumor growth and metastatic spread is abrogated or
      markedly reduced in the absence of neovascularization. Spleen T lymphocytes from
      tumor-bearing mice elicit a strong neovascular response. It is well known that
      certain T cell responses require the presence of active oxygen radicals. Because
      these metabolites are produced during tumor growth, we studied whether oxygen
      free radicals play a role in the angiogenesis induction by lymphocytes. In this
      study, we demonstrated that the administration of a free radical scavenger (EGb
      761) to tumor-bearing mice, blocked the angiogenic response and decreased the
      lung metastatic incidence. On the other hand, when normal lymphocytes were
      incubated with the xanthine-xanthine oxidase system (X-XO), a known superoxide
      anion generator, this elicited a dose-response positive angiogenic reaction in
      normal recipient mice. No angiogenic response was observed in the absence of X
      XO, or when EGb-761 or superoxide dismutase (SOD) plus catalase (CAT) were added
      to the incubation medium. These results suggest that free radicals are involved
      in some step of the angiogenic process, and that the EGb-761 treatments block
      this response due to the free radical scavenging activity of this compound.

PMID- 7527001
TI  - Distribution of vitronectin in plasma and liver tissue: relationship to chronic
      liver disease.
AB  - To clarify the clinical significance of vitronectin, we compared the
      concentration of plasma vitronectin with serum fibrous markers and liver function
      test values in patients with chronic liver diseases. We also evaluated the
      vitronectin content in the liver by means of enzyme-linked immunosorbent assay
      and the localization of vitronectin in liver tissue with enzyme
      immunohistochemistry. In chronic liver disease, the concentration of plasma
      vitronectin was significantly lower than that in healthy controls, being related
      to the severity of liver disease. The plasma levels of vitronectin showed no
      correlation to fibrous markers but a significant correlation with those of serum
      albumin and prothrombin time. On the other hand, the content of vitronectin in
      liver tissue was significantly increased in chronic liver disease compared with
      that in normal controls. In the normal liver, vitronectin was observed in the
      portal area by light microscopy. In chronic hepatitis and cirrhosis, vitronectin
      was found in the connective tissue around the portal and central veins and in the
      areas of piecemeal and focal necrosis. These findings suggested that vitronectin
      is deposited in injured tissue through the process of repair and fibrosis and
      plays an important role as an adhesive protein. Moreover, the lower levels of
      plasma vitronectin in chronic liver disease may be due to its decreased
      synthesis, deposition or both in injured tissue.

PMID- 7527002
TI  - Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading
      hepatocellular carcinoma, in the circulation: a possible predictor of metastatic
      hepatocellular carcinoma.
AB  - We attempted to detect circulating hepatocellular carcinoma by demonstrating
      hepatocyte-associated mRNA in the nuclear cell component of peripheral blood
      using nested reverse transcription-polymerase chain reaction because of the
      extremely small number of tumor cells in the circulation. Albumin mRNA was
      demonstrated not only in the liver tissue (hepatocytes) and HepG2 cells but also
      in nuclear cells of the blood from normal healthy volunteers (neutrophils and
      lymphocytes) by reverse transcription-polymerase chain reaction. In contrast,
      alpha-fetoprotein mRNA was demonstrated in the liver tissue, as well as in HepG2
      cells, but not in peripheral blood of normal healthy volunteers, indicating the
      possibility of using alpha-fetoprotein mRNA for detection of benign and malignant
      hepatocytes among the population of neutrophils and lymphocytes. alpha
      Fetoprotein mRNA in peripheral blood was detected in 17 of 33 cases of
      hepatocellular carcinoma (52%), 2 of 13 cases of cirrhosis (15%) and 2 of 17
      cases of chronic hepatitis (12%). alpha-Fetoprotein mRNA was not demonstrated in
      26 cases of normal healthy volunteers (0%). Among the patients with
      hepatocellular carcinoma, total volume of tumor tissue, maximum size of tumor and
      serum alpha-fetoprotein level were markedly increased in the patients with alpha
      fetoprotein mRNA in blood. In addition, alpha-fetoprotein mRNA was detected in
      the blood of all 6 patients showing metastasis at extrahepatic organs (100%), in
      contrast to 11 of 27 cases without metastasis (41%). From these results, we
      conclude that the presence of alpha-fetoprotein mRNA in peripheral blood may be
      an indicator of circulating malignant or benign hepatocytes, which might predict
      hematogenous spreading metastasis of tumor cells in patients with hepatocellular
      carcinoma.

PMID- 7527003
TI  - FK 506 renal toxicity and lack of detectable cytochrome P-450 3A in the liver
      graft of a patient undergoing liver transplantation.
AB  - Many commonly used drugs are substrates for hepatic cytochrome P-450 3A in human
      beings, and its role in the metabolism of potentially toxic immunosuppressants
      has been highlighted (cyclosporine, FK 506). One hundred fifty human liver grafts
      were biopsied before and after liver transplantation, and levels of cytochromes P
      450 3A, 1A2, 2D6 and 2C were estimated by means of the Western-blot technique and
      correlated with histological appearance, glycogen content and clinical course. In
      15 of the grafts, cyclosporine oxidase was also measured, and in 12 of 15
      recipients, urinary 6 beta-hydroxycortisol excretion was assayed. A wide range of
      cytochrome P-450 3A values were observed (25 to 366 arbitrary units/mg; mean, 105
      +/- 63 arbitrary units/mg). In one graft (no. 730) no cytochrome P-450 3A was
      detectable on immunoblotting, despite increasing homogenate concentrations. In
      this sample, cytochromes P-450 1A2, 2D6, and 2C were present in normal ranges.
      Levels of cyclosporine oxidase and 6 beta-hydroxycortisol in the urine specimens
      of the recipient were found to be low. The recipient of graft 730 experienced
      reversible complications of FK 506 therapy despite adherence to the
      administration protocol and drug plasma level in the normal range. The subsequent
      appearance of the cytochrome P-450 3A was associated with the consequent
      tolerance of oral FK 506. The absence of detectable amounts of P-450 3A in one
      biopsy from a donated human liver graft dramatically emphasizes the extreme range
      of this enzyme levels and has important clinical implications.

PMID- 7527004
TI  - Induction of hepatic Ito cell nitric oxide production after acute endotoxemia.
AB  - Nitric oxide is a highly reactive mediator released in the liver by hepatocytes,
      Kupffer cells and endothelial cells during endotoxin-induced inflammation. In
      this study we determined whether Ito cells also produce nitric oxide after
      exposure to endotoxin. For induction of endotoxemia, rats were injected
      intravenously with Escherichia coli lipopolysaccharide (2.5 mg/kg). Ito cells
      were isolated from the animals 48 hr later by means of in situ perfusion of the
      liver with protease and collagenase followed by purification on an
      arabinogalactan gradient. Ito cells from untreated and endotoxemic rats were
      found to produce low levels of nitric oxide in response to interferon-gamma. In
      both cell types, this response depended on L-arginine and was blocked by NG
      monomethyl-L-arginine, a specific nitric oxide synthase inhibitor. Cells from
      rats treated with endotoxin produced significantly more nitric oxide than did
      cells from untreated animals; this was due, at least in part, to increased
      expression of protein for an inducible form of nitric oxide synthase. These cells
      also responded to stimulation with lipopolysaccharide in vitro, as well as the
      combination of interferon-gamma and lipopolysaccharide, which was synergistic in
      stimulating nitric oxide production. Tumor necrosis factor-alpha and macrophage
      colony-stimulating factor were also found to stimulate nitric oxide production by
      Ito cells from endotoxemic rats. In addition, in these cells, tumor necrosis
      factor-alpha synergized with interferon-gamma in inducing nitric oxide
      production. The combination of interferon-gamma and lipopolysaccharide was also
      found to inhibit Ito cell DNA synthesis, as measured on the basis of [3H]
      thymidine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527006
TI  - Inhibition by recombinant human interleukin-6 of the glucagon-dependent induction
      of phosphoenolpyruvate carboxykinase and of the insulin-dependent induction of
      glucokinase gene expression in cultured rat hepatocytes: regulation of gene
      transcription and messenger RNA degradation.
AB  - The influence of recombinant human interleukin-6, the major mediator of the
      inflammatory response in liver, on the glucagon- and insulin-dependent induction
      of the phosphoenolpyruvate carboxykinase and glucokinase gene, respectively, was
      monitored on the level of gene transcription, mRNA abundance and enzyme activity
      in cultured rat hepatocytes. As control markers of the interleukin-6-induced
      acute-phase response the mRNA levels of the acute phase proteins alpha 2
      macroglobulin and beta-fibrinogen were determined. In cultured rat hepatocytes,
      recombinant human interleukin-6, added simultaneously with glucagon and insulin,
      lowered the maximal increase in glucagon-induced phosphoenolpyruvate
      carboxykinase mRNA levels after 2 hr and the maximal increase in glucokinase mRNA
      levels after 3 hr to about 30%, respectively. It inhibited the glucagon-induced
      increase in phosphoenolpyruvate carboxykinase gene transcription and
      phosphoenolpyruvate carboxykinase enzyme activity, as well as the insulin-induced
      increases in glucokinase gene transcription and glucokinase enzyme activity.
      Recombinant human interleukin-6 increased the mRNA levels of the acute-phase
      proteins alpha 2-macroglobulin and beta-fibrinogen gradually over 4 to 6 hr.
      Recombinant human interleukin-6, added 2 hr after glucagon or 3 hr after insulin
      at the maximum of the hormone-induced enzyme mRNA levels, almost doubled the
      decay rate of phosphoenolpyruvate carboxykinase mRNA and glucokinase mRNA. The
      results show that interleukin-6 induced the expression of inflammatory proteins
      and simultaneously inhibited the hormone-induced expression of enzymes of
      intermediary metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527005
TI  - Alteration in vascular reactivity in isolated aortic rings from portal vein
      constricted rats.
AB  - It has been suggested that increased production of nitric oxide by an inducible
      nitric oxide synthase isoenzyme is important in the pathogenesis of the vascular
      abnormalities seen in human beings and animals with portal hypertension. We
      investigated this hypothesis by studying the in vitro vascular reactivity of
      isolated aortic rings from portal vein-constricted and sham-operated rats. Aortic
      rings from portal vein-constricted rats exhibited significantly impaired
      contractility to phenylephrine and potassium chloride compared with control rats.
      Preincubation with the nitric oxide synthase inhibitor nitro-L-arginine methyl
      ester significantly increased contractility to phenylephrine and potassium
      chloride in both portal-hypertensive and control tissues, with greater effect in
      the portal-hypertensive rings. Despite nitro-L-arginine methyl ester, maximal
      contractions were still significantly smaller in the portal-hypertensive tissues.
      Vascular relaxation evoked by acetylcholine, but not by the endothelium
      independent vasodilator glyceryl trinitrate, was significantly impaired in the
      portal-hypertensive group. Our results demonstrate significant impairment in
      vascular function in aortic rings in this model of portal hypertension. The
      addition of a nitric oxide synthase inhibitor partly corrected these changes,
      suggesting that although nitric oxide is likely an important mediator, other
      factors may also be involved in the pathogenesis of these alterations in vascular
      function.

PMID- 7527008
TI  - Tumor marker for metastasis: searching for an abnormal needle in a haystack.

PMID- 7527007
TI  - Increased nitric oxide-dependent vasorelaxation in aortic rings of cirrhotic rats
      with ascites.
AB  - To assess whether aortic vessels of rats with cirrhosis and ascites possess an
      enhanced vascular response to endothelium-derived, nitric oxide-dependent
      vasodilators, we performed relaxation studies in isolated aortic rings of 21
      control rats and 24 rats with carbon tetrachloride-induced cirrhosis and ascites.
      We carried out studies after contracting the vessels with norepinephrine. We
      measured endothelium-dependent vasodilator response by administering increasing
      concentrations of acetylcholine (10(-6) to 10(-2) mol/L) and ADP (10(-7) to 10(
      4) mol/L). We evaluated endothelium-independent response by giving increased
      concentration of sodium nitrite (10(-5) to 10(-2) mol/L). The maximal absolute
      tension developed in response to norepinephrine was significantly decreased in
      cirrhotic rings (816 +/- 72 mg, p < 0.025) compared with control (1,425 +/- 75
      mg) rings. Dose-response curves for endothelium-dependent vasodilators were
      shifted to the left in aortic rings of cirrhotic rats, and EC50 for acetylcholine
      and ADP were significantly decreased in cirrhotic (0.8 +/- 0.15 mmol/L and 0.42
      +/- 0.16 mumol/L, p < 0.025 and p < 0.01, respectively) than in control rings
      (1.91 +/- 0.33 mmol/L and 3.09 +/- 0.82 mumol/L). In both acetylcholine- and ADP
      stimulated vessels, differences between cirrhotic and control rings disappeared
      after nitric oxide synthesis inhibition with N omega-nitro-L-arginine (10(-4)
      mol/L). No difference in the relaxing effect of sodium nitrite was observed
      between cirrhotic and control rings. These results therefore demonstrate for the
      first time enhanced in vitro vascular responsiveness to nitric oxide-dependent
      vasodilators in rats with cirrhosis and ascites, giving further support to the
      concept that nitric oxide activity is increased in cirrhosis.

PMID- 7527009
TI  - Predictive value of serum alpha-fetoprotein in cirrhosis.

PMID- 7527011
TI  - The development of natural killer (NK) cells from Thy-1loLin-Sca-1+ stem cells:
      acquisition by NK cells in vivo of the homing receptor MEL-14 and the integrin
      Mac-1.
AB  - The present study aimed to follow the development of natural killer (NK) cells in
      lethally irradiated BA mice reconstituted with 500 syngeneic Thy 1.1loLin-Sca-1+
      stem cells. The proportions of NK 1.1+ lymphoid cells were assessed from smears
      of cell suspensions from the spleen and bone marrow by means of
      immunofluorescence microscopy, at 7, 9, 11, 14, 17, 21, 24 and 28 days after stem
      cell injection. At the same intervals, moreover, the proportions of NK 1.1+
      lymphoid cells bearing either the homing receptor recognized by mAb MEL-14, or
      the integrin Mac-1 were recorded using double immunofluorescence microscopy,
      labelling variously with fluorescein isothiocynate and avidin-Texas Red. The
      results demonstrate that NK 1.1+ lymphoid cells re-appear by 11 (spleen) to 14
      (bone marrow) days after injecting syngeneic Thy 1.1loLin-Sca-1+ stem cells.
      Moreover, in the absence of apparent stimulation, the newly developed NK 1.1+
      lymphoid cells spontaneously express the homing receptor MEL-14 and the integrin
      Mac-1. The very similar patterns of acquisition of these latter 2 molecules on NK
      1.1+ cells in the spleen during their recovery in the post-stem cell injection
      period suggests that MEL-14 and Mac-1 may co-express on the same NK 1.1+ cells.
      The absence, or low levels of both molecules on the newly developed NK 1.1+ cells
      while still in the bone marrow suggests that NK cells may progressively acquire
      these molecules outside that organ, en route to and/or within the vasculature of
      the spleen, their normal, primary destiny.

PMID- 7527010
TI  - Expression of tenascin, type IV collagen and laminin during human intrahepatic
      bile duct development and in intrahepatic cholangiocarcinoma.
AB  - Expression of tenascin, type IV collagen and laminin during human intrahepatic
      bile duct development and in cholangiocarcinoma was examined by
      immunohistochemistry. In the developing hilar bile ducts, tenascin was expressed
      in the mesenchyme around the epithelial cells migrating from the ductal plate
      into the mesenchyme at 10-14 weeks of gestation. Tenascin was also expressed in
      the mesenchyme around newly formed hilar bile ducts at 15-20 weeks of gestation,
      but its expression disappeared after 21 weeks of gestation. Type IV collagen and
      laminin were expressed around the ductal plate, around epithelial cells migrating
      from the ductal plate into the mesenchyme, and around newly formed hilar bile
      ducts, and their expression was present throughout fetal life. By contrast, in
      the development of peripheral bile ducts, tenascin expression was not found. Type
      IV collagen and laminin were identified around the ductal plate, migrating
      epithelial cells and peripheral bile ducts. In cholangiocarcinoma, tenascin and
      type IV collagen were expressed in the stroma, but laminin was not identified.
      These findings suggest that tenascin may play a role in hilar bile duct
      development and that type IV collagen and laminin may play a role in both hilar
      and peripheral bile duct development. Expression of tenascin and type IV collagen
      in the stroma of cholangiocarcinoma may be the result of malignant transformation
      of intrahepatic biliary epithelium; tenascin in peritumoral stroma may stimulate
      carcinoma cell proliferation and growth in cholangiocarcinoma.

PMID- 7527012
TI  - Protective effect of recombinant neutrophil elastase inhibitor (R-020) on sepsis
      induced organ injury in rat.
AB  - Severe inflammatory responses after major surgeries, trauma, and infection
      develop multiple organ dysfunction. In the mechanisms of the pathogenesis of
      these responses, activated neutrophils are thought to be important in terms of
      their ability to produce various kinds of proteinases, which can degrade various
      proteins constructing human tissues. Among their proteinases, neutrophil elastase
      is the strongest serine proteinase secreted from activated neutrophils. Thus, we
      examined in this study the inhibitory effect and therapeutic efficacy of newly
      produced recombinant human Kunitz-type proteinase inhibitor (R-020), which coded
      the second domain of human urinary trypsin inhibitor. R-020 was effective in
      significantly improving the survival rate after induction of the rat lethal
      peritonitis model (cecal ligation and puncture-induced septic shock model). We
      suggest that various serine proteinases are implicated in the pathogenesis of
      neutrophil-related multiple organ failure and that recombinant human Kunitz-type
      proteinase inhibitor might be effective in the treatment of these kinds of organ
      dysfunction.

PMID- 7527014
TI  - Cyclic hexapeptide NK-2 antagonists.
AB  - The synthesis of 11 cyclic hexapeptides, some of which contain a carbohydrate
      side chain moiety, is described in this paper. A glycosylamine was coupled
      without hydroxyl protecting groups either directly or via a butyric acid spacer
      to the side chain of glutamic acid, leading to beta-N-glycosylated peptides. All
      peptides described are selective NK-2 antagonists. The binding affinity to the NK
      2-receptor ranges from 7 x 10(-7) to 1 x 10(-8) M, whereas at the NK-1 receptor
      the IC50 was > 10(-5) M with the exception of cyclo(-Lys(Boc)-Trp-Phe-Gly-Leu-D
      Leu-) (I), which shows low affinity to the NK-1 receptor (IC50 = 9 x 10(-6) M).
      The antagonist activity is determined in the hamster trachea assay. pA2-Values
      range from 7.1 to 7.8. The results demonstrate the broad range of side chains
      which can be accommodated at the glutamine position without a major drop in
      activity. The different charges of the lysine and the glutamic acid peptides
      indicate that the interaction with the receptor at this position is not
      determined by ionic forces. Rather, we expect that conformational flexibility
      allows differently charged amino acid residues to be accommodated by the
      receptor.

PMID- 7527013
TI  - Intratracheal administration of endotoxin and cytokines: VIII. LPS induces E
      selectin expression; anti-E-selectin and soluble E-selectin inhibit acute
      inflammation.
AB  - E-selectin is an inducible endothelial adhesion molecule that binds neutrophils.
      E-selectin mRNA is not constitutively detectable in the lungs of rats.
      Intratracheal injection of LPS induces pulmonary E-selectin mRNA expression at 2
      4 h. Intratracheal injection of LPS followed at 2 and 4 h by intravenous
      injection of mouse F(ab')2 or F(ab') anti-E-selectin monoclonal antibody inhibits
      the emigration of neutrophils into the bronchoalveolar space at 6 h by 50-70%.
      TNF and IL-6 bioactivity are not decreased in bronchoalveolar lavage fluid after
      treatment with anti-E-selectin antibody as compared to controls, suggesting that
      the anti-E-selectin does not affect the magnitude of the LPS-initiated cytokine
      cascade. Intratracheal injection of LPS followed at 2 and 4 h by intravenous
      injection of soluble E-selectin inhibits neutrophilic emigration at 6 h by 64%,
      suggesting that endogenous soluble E-selectin shed from activated endothelium may
      play a role in the endogenous down-regulation of acute inflammation. E-selectin
      mediated adhesion of neutrophils to endothelium appears crucial to the full
      development of the acute inflammation response.

PMID- 7527015
TI  - BPTI backbone variants and implications for inhibitory activity.
AB  - Structural variants of BPTI were synthesized en route an enzymatic-chemical
      semisynthesis. The P1-P2 amide bond of the inhibitor molecule, which, as donor,
      contributes a hydrogen bond towards trypsin in the enzyme-inhibitor complex, was
      replaced by either a ketomethylene function or an ester bond yielding molecules
      with inhibitory activity. The two backbone-mutated BPTI derivatives showed
      increased dissociation constants of their respective trypsin complexes, obviously
      due to the lack of a single hydrogen-bond interaction in the enzyme-inhibitor
      complex.

PMID- 7527017
TI  - Comparative study of experimentally induced benign and atypical hyperplasia in
      the ventral prostate of different rat strains.
AB  - The induction of prostatic lesions in the rat by hormonal manipulation and/or
      chemical carcinogens in different strains is well documented in literature.
      However, the selection of a strain for such studies was merely based on the
      laboratory husbandry facilities rather than on the animal genotype. It is well
      accepted that the morphology and function of the prostate exhibit a marked
      species-specific differences that makes extrapolation to other animals and man
      difficult. Our group has developed an experimental model for the study of rat
      prostatic hyperplasia and/or dysplasia induced by citral--a flavor constituent.
      Previous observations have revealed that the Wistar rat ventral prostate is
      reactive to citral, especially during its adolescent growth period as well as
      during the redifferentiation stage among postcastrated rats treated with
      exogenous testosterone. The present study presents data on the ventral prostate
      susceptibility of three additional strains selected by their interrelated
      endocrine morbidity. In order to facilitate an objective comparative analysis of
      the prostatic lesions a histopathological score chart was elaborated. The present
      findings showed that the Wistar and Sprague-Dawley strains were the most
      susceptible to developing benign and atypical prostatic hyperplasia both in
      intact and postcastrated rats. The F344 and ACl/Ztm rat strains remained
      refractory toward all of these treatments. Our data provide evidence that the
      strain genotype and, more precisely, their endocrine background, play a
      determinative role in the prostatic responsiveness towards citral. It is
      suggested that additional consideration be given to the selection of an adequate
      animal strain when studying experimental neoplastic transformation, especially
      when hormonal interactions might be involved.

PMID- 7527018
TI  - Immunocytochemical detection of choline acetyltransferase in the human organ of
      Corti.
AB  - In the mammalian cochlea acetylcholine has been considered a major
      neurotransmitter of the lateral and medial efferent fibers. The aims of the
      present study were to investigate the expression of ChAT in the human cochlea and
      to develop a new method for immunohistochemical investigations in the human
      cochlea both at the light and electronmicroscopic level. We thus examined the
      ChAT-like immunoreactivity in the human inner ear using light and electron
      microscopy with a pre-embedding technique. Our present results agree with the
      previously published data acquired in rodent species. The ChAT-like
      immunostaining could be found in the inner spiral fibers, the inner spiral
      bundle, tunnel crossing fibers and at the base of the outer hair cells. No
      staining was noted in the negative controls experiments, while rat cochleas used
      as positive controls showed the usual ChAT-like immunostaining as described
      above. The main difference between human and rat cochleas was that the efferent
      nerve supply seems to be less pronounced in the human cochleas.

PMID- 7527016
TI  - Neuron-associated class III beta-tubulin, tau, and MAP2 in the D-283 Med cell
      line and in primary explants of human medulloblastoma.
AB  - The D283 Med human medulloblastoma cell line and primary explants of five
      surgically excised medulloblastomas were cultured using a three-dimensional
      Gelfoam matrix system. The cultures were evaluated immunohistochemically for a
      series of antigenic determinants associated with neuronal or glial
      differentiation. Focal immunolocalization of class III beta-tubulin, microtubule
      associated protein 2 (MAP2), and to a lesser degree tau, was demonstrated in all
      cultures. Class III beta-tubulin isotype, MAP2, and tau protein were also
      detected by immunoblot in Gelfoam matrix cultures, monolayer cultures, and
      suspension cultures of D283 Med cells. Staining for neurofilament protein
      epitopes was highly variable, even among different cultures derived from the same
      original tumour, but time-dependent changes in neurofilament protein, which may
      have reflected neuronal differentiation, were not consistently shown. Widespread
      gamma-enolase and focal synaptophysin reactivities were visualized in all
      cultures, but no S-antigen staining was detected. Leu 7 labelling was variably
      present in half of the cultures of D283 Med cells, but was more abundant in
      explants derived from four of the five original tumours. Vimentin was
      consistently found in D283 Med cultures at all time points. No immunoreactivity
      for glial fibrillary acidic protein was detected in the D283 Med cell line.
      Conversely, staining for this protein was demonstrated in scattered astrocytic
      cells in the surgical specimens of all five medulloblastomas. Concomitant with
      increased time in culture, three of the primary tumours displayed increased
      numbers of glial fibrillary acidic protein-positive cells when cultured in the
      Gelfoam system, but the other two tumours had a minimal astrocytic
      component.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527019
TI  - Identification of a glutamate/aspartate transporter in the rat cochlea.
AB  - The neurotransmitter at the synapses between hair cells and spiral ganglion cells
      in the cochlea is probably L-glutamate or a similar excitatory amino acid.
      Glutamate uptake by nerve terminals and glial cells is an important component of
      neurotransmission at glutamatergic synapses of the central nervous system, for
      providing a reservoir of transmitter or transmitter precursors and the
      termination of the released glutamate. Hair cell synapses are not surrounded by
      glial cells, therefore, the uptake mechanism for glutamate in the cochlea may be
      unique. cDNA was synthesized from total RNA isolated separately from the rat
      organ of Corti, spiral ganglia, and lateral wall tissues. The expression of a
      glutamate/aspartate transporter (GLAST) was detected by DNA amplification with
      the polymerase chain reaction. The other two members of glutamate transporters in
      this family were not detected by this method. A partial cDNA encoding to GLAST
      was identified by sequence analysis in a rat cochlear cDNA library. Data
      concerning the expression and the molecular structure of the glutamate
      transporter GLAST in the cochlea may provide important information regarding the
      neurotransmission process at the hair cell-afferent synapses.

PMID- 7527021
TI  - CD5+ chronic B-cell leukemia with features intermediate to chronic lymphocytic
      leukemia and hairy cell leukemia.
AB  - Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are
      differentiated B-cell leukemias with well-described clinical, morphologic, and
      immunologic characteristics. We encountered two patients with indolent chronic B
      cell leukemia showing overlapping features of these malignancies. The patients
      had progressive splenomegaly, minimal lymphadenopathy, and abnormal lymphoid
      cells with abundant cytoplasm and villi, which were strongly positive for surface
      antigens CD22 and CD11c, features associated with HCL. However, blood counts
      showed lymphocytosis without neutropenia and monocytopenia, and the bone marrow
      biopsies demonstrated tightly aggregated nodules of lymphocytes. In addition, the
      lymphoid cells were dual positive for CD19 and CD5, displaying weak-to-moderately
      positive monoclonal surface immunoglobulin, findings strongly suggestive of CLL.
      One patient failed to respond to therapy with chlorambucil and prednisone. The
      second patient showed a partial response to treatment with 2
      chlorodeoxyadenosine. We compare our patients with similar variants of
      differentiated B-cell leukemias reported in the literature, including disorders
      described as hairy cell variant (HCL-V) or splenic lymphoma with villous
      lymphocytes (SLVL).

PMID- 7527022
TI  - Risperidone in adolescents.

PMID- 7527020
TI  - Morphologic and quantitative alterations in hematopoietic cells associated with
      growth factor therapy: review of the literature.

PMID- 7527023
TI  - A novel RING finger protein interacts with the cytoplasmic domain of CD40.
AB  - CD40 is a member of the tumor necrosis factor receptor family and, like other
      members, it appears to possess no intrinsic signaling capacity (e.g. kinase
      activity), suggesting that signal transduction is likely mediated by associating
      molecules. To identify such molecules, we have utilized the yeast two-hybrid
      system to clone cDNAs encoding proteins that bind the CD40 cytoplasmic domain.
      One such interacting protein, designated CD40-binding protein, has a N-terminal
      RING finger motif that is found in a number of DNA-binding proteins, including
      the V(D)J recombination activating gene RAG1. In addition, it contains a
      prominent central coiled-coil segment that may allow homo- or hetero
      oligomerization. The C terminus possesses substantial homology to the tumor
      necrosis factor receptor-associated factor (TRAF) domain that is found in two
      proteins (TRAF1 and TRAF2) that associate with the cytoplasmic domain of the
      related 75-kDa tumor necrosis factor receptor. This is the first identification
      of a molecule that interacts with CD40 and whose sequence suggests a potential
      role in signaling.

PMID- 7527024
TI  - Intercellular adhesion molecule-1 is a cell surface receptor for hyaluronan.
AB  - Our laboratory has previously characterized and purified the hyaluronan receptor
      by hyaluronan affinity chromatography of rat liver endothelial cells. We have now
      isolated the receptor from whole rat liver and have obtained sufficient
      quantities for amino acid sequence analysis. Four peptides of various lengths
      were obtained from affinity-purified receptor and found to have identity with rat
      intercellular adhesion molecule-1. This glycoprotein is normally expressed in low
      amounts on the endothelial cells, but is up-regulated in inflamed and malignant
      tissues, and mediates cell-cell adhesion as a ligand for lymphocyte function
      associated antigen-1 and the macrophage-associated Mac-1. The affinity of
      intercellular adhesion molecule-1 for hyaluronan is likely to have important
      implications for cell adhesion in normal and in disease states such as
      inflammation, atherosclerosis, and cancer.

PMID- 7527025
TI  - Growth hormone stimulates tyrosine phosphorylation of insulin receptor substrate
      1.
AB  - Growth hormone (GH) produces insulin-like effects in rat adipocytes that have
      been deprived of GH for at least 3 h. The effect of a saturating concentration of
      GH is qualitatively and quantitatively similar to that produced by 2-4 ng/ml
      insulin but differs from that of insulin in the respect that adipocytes become
      refractory to prolonged or repeated stimulation with GH. Since activation of
      tyrosine kinase is an early event in the action of both hormones, we investigated
      the possibility that GH stimulation of tyrosine phosphorylation of some protein
      in the insulin transduction cascade might result in the similar effect of the two
      hormones. Adipocytes were preincubated for 3 h in the absence of hormones and
      then reincubated without or with 500 ng/ml GH or 4-400 ng/ml insulin for 10 min.
      The cells were lysed with an equal volume of buffer containing 1% SDS and
      preheated to 100 degrees C. Proteins were separated by electrophoresis on 7.5%
      polyacrylamide gels and transferred to nitrocellulose membranes, and tyrosine
      phosphorylated proteins were detected using anti-phosphotyrosine antiserum
      coupled to horseradish peroxidase and reagents to produce chemiluminescence. The
      faint band seen at 185 kDa in control lanes was increased by GH treatment in five
      independent experiments. Insulin produced a similar effect at a concentration of
      4 ng/ml, and phosphorylation increased in a dose-related manner in cells treated
      with higher concentrations of insulin. A prominent approximately 95-kDa band that
      is probably not the beta subunit of the insulin receptor was also seen in GH
      treated cells. The beta subunit of the insulin receptor has similar
      electrophoretic mobility to the 95-kDa protein, but was not phosphorylated to an
      extent that allowed detection when insulin was added at concentrations below 400
      ng/ml. Phosphorylation of the 185- and 95-kDa bands was evident within 1 min
      after addition of GH, persisted for at least 30 min, and was equally prominent in
      sensitive and refractory cells. Antiserum to IRS-1 immunoprecipitated the
      tyrosine-phosphorylated 185-kDa protein. The data suggest that IRS-1 is a
      substrate for a GH-activated tyrosine kinase, possibly JAK-2, which may account
      for the insulin-like effects of GH. The data further suggest that refractoriness
      to insulin-like stimulation by GH may result from an additional GH-dependent
      action that is distinct from phosphorylation of IRS-1.

PMID- 7527026
TI  - Glucagon and glucagon-like peptide 1: selective receptor recognition via distinct
      peptide epitopes.
AB  - Glucagon and glucagon-like peptide 1 (GLP-1) are homologous peptide hormones that
      are recognized by likewise homologous, but highly selective receptors. Analogs of
      glucagon and GLP-1, in which the divergent residues were systematically
      exchanged, were employed to identify the structural requirements for their
      selective receptor recognition. Substitutions in the NH2-terminal part of the
      glucagon molecule with the corresponding GLP-1 residues, as for example in
      [Ala2,Glu3]-glucagon and [Val10,Ser12]glucagon, reduced the binding affinity for
      the glucagon receptor several hundred-fold without increasing the affinity for
      the GLP-1 receptor. In contrast, introduction of GLP-1 residues into the far COOH
      terminal part of the glucagon molecule, e.g. [Val27,Lys28,Gly29,Arg30]glucagon,
      had a minimal effect on recognition of the glucagon receptor, but improved the
      affinity of the analog for the GLP-1 receptor up to 200-fold. Similarly,
      substitutions in especially the far COOH-terminal part of the GLP-1 molecule with
      the corresponding glucagon residues, e.g. des-Arg30-[Met27,Asn28,Thr29]GLP-1,
      decreased the affinity for the GLP-1 receptor several hundred-fold (IC50 = 0.4
      190 nM) without increasing the affinity for the glucagon receptor. Conversely,
      substitutions in the NH2-terminal part of the GLP-1 molecule impaired the
      affinity for the GLP-1 receptor only moderately. We conclude that the selective
      recognition of the glucagon and GLP-1 receptors is determined by residues located
      at opposite ends of the homologous peptide ligands. This conclusion is supported
      by the observation that a "chimeric" peptide consisting of the NH2-terminal part
      of the glucagon molecule joined to the COOH-terminal part of the GLP-1 molecule
      was recognized with high affinity by both receptors.

PMID- 7527028
TI  - A Lymnaea stagnalis gene, with sequence similarity to that of mammalian beta 1-
      >4-galactosyltransferases, encodes a novel UDP-GlcNAc:GlcNAc beta-R beta 1-->4-N
      acetylglucosaminyltransferase.
AB  - A cDNA encoding a novel glycosyltransferase, that may be involved in a variant
      pathway for the synthesis of complex type oligosaccharide chains, was cloned from
      the pond snail Lymnaea stagnalis. By heterologous hybridization, using bovine
      beta 1-->4-galactosyltransferase cDNA as probe, a genomic clone from a snail
      library was isolated. This genomic clone was subsequently used to clone the
      corresponding cDNA from a prostate gland library. The isolated cDNA encodes a
      polypeptide of 490 amino acids with a type II membrane protein topology typical
      for glycosyltransferases. The carboxyl-terminal part, encoding the putative
      catalytic domain, reveals considerable sequence similarity with the corresponding
      region of mammalian beta 1-->4-galactosyltransferases, suggesting an evolutionary
      relationship. Expression of this cDNA in COS cells and insect cells revealed that
      the encoded enzyme transfers GlcNAc, rather than Gal or GalNAc, from the
      corresponding nucleotide sugars to several beta-N-acetylglucosaminides.
      Structural characterization by 1H NMR spectroscopy of products formed in vitro
      demonstrated that the enzyme can be identified as a UDP-GlcNAc:GlcNAc beta-R beta
      1-->4-N-acetylglucosaminyl-transferase. A new family of glycosyltransferases has
      hereby been discovered, consisting of enzymes that act on acceptor substrates
      with a terminal beta-linked GlcNAc residue and establish a beta 1-->4-linkage,
      but have a different nucleotide sugar requirement.

PMID- 7527030
TI  - Transforming growth factor beta isoform 2-specific high affinity binding to
      native alpha 2-macroglobulin. Chimeras identify a sequence that determines
      affinity for native but not activated alpha 2-macroglobulin.
AB  - Transforming growth factor beta 2 (TGF-beta 2) is less potent than TGF-beta 1 in
      some endothelial cell proliferation assays due to the greater tendency of TGF
      beta 2 to bind alpha 2-macroglobulin (alpha 2M). Substitution of TGF-beta 1
      residues 40-47 into the TGF-beta 2 sequence yields a chimeric molecule that, like
      TGF-beta 1, expresses activity that is not substantially affected by serum alpha
      2M (Burmester, J. K., Qian, S. W., Roberts, A. B., Huang, A., Amatayakul
      Chantler, S., Suardet, L., Odartchenko, N., Madri, J. A., and Sporn, M. B. (1993)
      Proc. Natl. Acad. Sci. U.S.A. 90, 8628-8632). In this investigation, we studied
      the binding of TGF-beta chimeras, which contain TGF-beta 1 residues 40-47, to
      both major conformations of human alpha 2M under apparent equilibrium conditions.
      Native alpha 2M, the primary form of this protein in serum, bound TGF-beta 2/beta
      1 (40-82) and TGF-beta 2/beta 1 (40-47) with low affinity. The apparent KD values
      for the two chimeras and native alpha 2M were 310 and 330 nM, respectively. These
      values were much higher than the KD determined for TGF-beta 2 and native alpha 2M
      (11 nM) and equivalent to the KD determined for TGF-beta 1 and native alpha 2M.
      By contrast, both TGF-beta chimeras bound alpha 2M-methylamine, an altered
      conformation of alpha 2M, with high affinity (16 and 19 nM), which is
      characteristic of TGF-beta 2 and not TGF-beta 1. Fetal bovine heart endothelial
      cell DNA synthesis was inhibited to a similar degree by TGF-beta 1, TGF-beta 2,
      TGF-beta 2/beta 1 (40-82), and TGF-beta 2/beta 1 (40-47) in the presence of
      dilute (0.2%) fetal bovine serum. When 0.07 microM alpha 2M-methylamine was
      added, the activities of TGF-beta 2, TGF-beta 2/beta 1 (40-82), and TGF-beta
      2/beta 1 (40-47) were significantly counteracted while the activity of TGF-beta 1
      was unchanged, as would be predicted by the equilibrium binding analyses. These
      studies indicate that the TGF-beta structural elements, which mediate binding to
      native alpha 2M and conformationally transformed alpha 2M, are not equivalent.
      Residues 40-47 are critical in determining affinity for native alpha 2M but are
      less important in determining affinity for alpha 2M-methylamine.

PMID- 7527029
TI  - Signaling-induced association of a tyrosine-phosphorylated 36-kDa protein with
      p50csk.
AB  - The protein-tyrosine kinase, p50csk, is thought to participate in the regulation
      of signal transduction pathways by catalyzing the phosphorylation of the Src
      related protein-tyrosine kinases on a negative regulatory tyrosine residue
      located near the COOH terminus. To study possible mechanisms by which the
      activity of p50csk might be regulated, we searched for p50csk-interacting
      proteins in human erythroleukemia cells. We found that in response to the
      treatment of cells with pervanadate, a potent inhibitor of protein tyrosine
      phosphatases, or to the cross-linking of Fc gamma RIIA receptors, p50csk becomes
      tightly associated with a 36-kDa protein (p36). This association is dependent on
      the tyrosine phosphorylation of p36 and involves its interaction with the SH2
      domain of p50csk.p36 can be phosphorylated in vitro by p50csk or by a full-length
      GST-Csk fusion protein expressed in Escherichia coli. Tyrosine-phosphorylated p36
      is found exclusively in the particulate membrane fraction of the cell. Conditions
      that induce the formation of the p50csk.p36 complex promote the appearance of
      p50csk in the particulate fraction. These data suggest that the association
      between p50csk and p36 serves to translocate the normally cytosolic p50csk to the
      membrane, where it presumably interacts with its physiologically relevant
      substrates.

PMID- 7527032
TI  - Phosphopeptide occupancy and photoaffinity cross-linking of the v-Src SH2 domain
      attenuates tyrosine kinase activity.
AB  - Phosphorylation of c-Src at carboxyl-terminal Tyr-527 suppresses tyrosine kinase
      activity and transforming potential, presumably by facilitating the
      intramolecular interaction of the C terminus of Src with its SH2 domain. In
      addition, it has been shown previously that occupancy of the c-Src SH2 domain
      with a phosphopeptide stimulates c-Src kinase catalytic activity. We have
      performed analogous studies with v-Src, the transforming protein from Rous
      sarcoma virus, which has extensive homology with c-Src. v-Src lacks an
      autoregulatory phosphorylation site, and its kinase domain is constitutively
      active. Phosphopeptides corresponding to the sequences surrounding c-Src Tyr-527
      and a Tyr-Glu-Glu-Ile motif from the hamster polyoma virus middle T antigen
      inhibit tyrosine kinase activity of baculovirus-expressed v-Src 2- and 4-fold,
      respectively. To determine the mechanism of this regulation, the Tyr-527
      phosphopeptide was substituted with the photoactive amino acid p
      benzoylphenylalanine at the adjacent positions (N- and C-terminal) to
      phosphotyrosine. These peptides photoinactivate the v-Src tyrosine kinase 5-fold
      in a time- and concentration-dependent manner. Furthermore, the peptides cross
      link an isolated Src SH2 domain with similar rates and specificity. These data
      indicate that occupancy of the v-Src SH2 domain induces a conformational change
      that is transmitted to the kinase domain and attenuates tyrosine kinase activity.

PMID- 7527027
TI  - GAP-43 controls the availability of secretory chromaffin granules for regulated
      exocytosis by stimulating a granule-associated G0.
AB  - Besides having a role in signal transduction, heterotrimeric G proteins may also
      be involved in membrane trafficking events as suggested by their presence in
      specific intracellular compartments. In chromaffin cells, G alpha 0 is associated
      with secretory organelles, and its activation inhibits exocytosis. Although
      plasma membrane-bound G proteins are activated by cell-surface receptors, the
      intracellular proteins controlling organelle-associated G proteins are currently
      unknown. GAP-43, a neuronal protein enriched in axonal growth cones and
      presynaptic terminals, is one possible candidate since it can directly stimulate
      purified G0. We have investigated the interaction of adrenal medullary GAP-43
      with chromaffin granule-associated G0 and its effect on catecholamine secretion.
      Cytosolic and depalmitoylated membrane-extracted GAP-43 were found to stimulate
      guanine nucleotide binding and exchange activity in chromaffin granule membranes.
      In permeabilized chromaffin cells, both forms of GAP-43 blocked calcium-dependent
      exocytosis, and this effect was inhibited by specific antibodies against G alpha
      0. A synthetic peptide corresponding to the GAP-43 domain that interacts with G0
      inhibited catecholamine secretion. This effect could be selectively reversed by
      the COOH-terminal peptide of G alpha 0. These results indicate that GAP-43 may be
      an endogenous pseudoreceptor for the secretory granule-bound form of G0 and can
      thereby control calcium-regulated exocytosis in chromaffin cells.

PMID- 7527031
TI  - The C-terminal peptide produced upon proteolytic activation of the cytolytic
      toxin aerolysin is not involved in channel formation.
AB  - The channel-forming toxin aerolysin is secreted by Aeromonas hydrophila as a
      protoxin that can be activated by nicking with endoproteinase Lys-C after Lys-427
      near the C terminus of the protein. The fate of the 43-amino acid peptide distal
      to the activation site was investigated. A cysteine was introduced into the C
      terminal region by replacing Ile-445, and another replaced Gly-202, which is on
      the proximal side of the activation site. In a double mutant, the two new
      cysteines were close enough in the folded molecule to form an intrachain 202-445
      disulfide bond. Tryptophan fluorescence measurements on wild type and the 2
      single cysteine mutants indicated that activation results in exposure of at least
      1 tryptophan residue, leading to the conclusion that the peptide moves with
      respect to the protein when it is produced. This was supported by the observation
      that upon activation there was a decrease in energy transfer between a tryptophan
      in the bulk of the protein and a probe attached to Cys-445. The peptide could be
      separated from active toxin by several methods, indicating that it leaves the
      protein when it is produced, and that it plays no further role in the process of
      channel formation.

PMID- 7527035
TI  - Identification of a hormonally regulated protein tyrosine phosphatase associated
      with bone and testicular differentiation.
AB  - Absence of the tyrosine kinase activity of c-src and c-fms results in impairment
      of bone remodeling. Such dysfunction underscores the importance of tyrosine
      phosphorylation, yet the role of protein tyrosine phosphatases in bone metabolism
      remains unexamined. We have isolated the cDNA for a novel receptor-like tyrosine
      phosphatase expressed in bone and testis named osteotesticular protein tyrosine
      phosphatase (OST-PTP). The deduced 1711-residue protein possesses an
      extracellular domain with 10 fibronectin type III repeats and a cytoplasmic
      region with two catalytic domains. In primary rat osteoblasts, the 5.8-kilobase
      OST-PTP transcript is up-regulated in differentiating cultures and down-regulated
      in late stage mineralizing cultures. In addition, a presumed alternate transcript
      of 4.8-5.0 kilobases, which may lack PTP domains, is present in proliferating
      osteoblasts, but not detectable at other stages. Parathyroid hormone, a modulator
      of bone function, as well as cyclic AMP analogues, increase OST-PTP mRNA 5-8-fold
      in UMR 106 cells. In situ hybridization of adult rat testis revealed stage
      specific expression of OST-PTP. OST-PTP may function in signaling pathways during
      bone remodeling, as well as serve a broader role in cell interactions associated
      with differentiation in bone and testis.

PMID- 7527036
TI  - Transforming growth factor beta down-regulates Src family protein tyrosine kinase
      signaling pathways.
AB  - Transforming growth factor beta (TGF beta) inhibits the proliferation of a wide
      range of cell types through interaction with its cell surface receptor (R-TGF
      beta). R-TGF beta possesses serine/threonine kinase activity rather than the
      tyrosine kinase activity normally associated with peptide growth factor
      receptors; nevertheless, TGF beta triggers a signaling pathway that leads to the
      repression of transcription factors, which appear to mediate the action of
      receptor tyrosine kinases within the nucleus. Accumulating evidence has also
      shown that the nonreceptor protein tyrosine kinases of the Src family play
      essential roles in the signal transduction pathways that regulate cell
      proliferation, differentiation, and function. Here, we investigate whether
      signals initiated by R-TGF beta are transduced, at least in part, through members
      of the Src family of tyrosine kinases. Treatment of the responsive human prostate
      carcinoma cell line PC3 with TGF beta induces a rapid and specific decrease in
      cellular levels of pp60Src and pp53/56Lyn and a corresponding decrease in their
      protein kinase activity when the assays were performed in vitro using the
      exogenous substrate enolase. Consistent with suppression of pp60Src and
      pp53/56Lyn kinase activity, TGF beta also caused a substantial intracellular
      accumulation of the unphosphorylated form of SH2-containing protein (SHC), a
      substrate of the Src family kinases. This was paralleled by decreased formation
      of a complex between the adaptor protein known as growth factor receptor-bound
      protein 2 and SHC. These results suggest, for the first time, that TGF beta
      induces down-regulation of Src family kinases, leading to disruption of the SHC
      growth factor receptor-bound protein 2 complex. These events may play a crucial
      role in the negative regulation of Ras, as well as in the control of downstream
      effector molecules involved in the regulation of cell growth.

PMID- 7527033
TI  - DNA damage induced by bleomycin, neocarzinostatin, and melphalan in a precisely
      positioned nucleosome. Asymmetry in protection at the periphery of nucleosome
      bound DNA.
AB  - The antitumor drugs bleomycin, neocarzinostatin, and melphalan all damage DNA by
      mechanisms which involve binding in the minor groove. In order to examine at high
      resolution the modulating effects of chromatin structure on the action of these
      drugs, an end-labeled DNA fragment from the Xenopus laevis 5 S rRNA gene was
      reconstituted with histone octamers to form a precisely positioned nucleosome.
      For each drug, DNA damage at specific sequence positions in the fragment was then
      compared for nucleosome-bound versus naked DNA. Reconstitution into nucleosomes
      resulted in a marked inhibition of the DNA cleavage induced by bleomycin (5-fold)
      and neocarzinostatin (2.4-fold) in the central region of nucleosomal DNA.
      However, at the periphery of nucleosome-bound DNA, a distinct asymmetry was
      apparent, with marked inhibition of cleavage toward the upstream side, but little
      if any inhibition toward the downstream side, which overlaps the binding site of
      the transcription factor TFIIIA. In the case of melphalan, alkylation at adenine
      N-3 was inhibited by nearly 2-fold throughout the nucleosome, whereas alkylation
      at guanine N-7 was either slightly inhibited or slightly enhanced, depending on
      sequence position. None of the drugs showed the 10-base pair periodicity
      characteristic of hydroxyl radical-induced cleavage of nucleosomal DNA. The
      results are consistent with a model in which minor groove sites in nucleosome
      bound DNA remain relatively accessible to small molecules, even where the minor
      groove faces the histone core, and in which drug-induced DNA damage is inhibited
      by conformational constraints imposed on DNA by nucleosome structure.
      Furthermore, the degree of such constraints appears to be sequence-dependent, at
      least near the periphery of nucleosome-bound DNA.

PMID- 7527034
TI  - Tyrosine-containing sequence motifs of the human immunoglobulin G receptors
      FcRIIb1 and FcRIIb2 essential for endocytosis and regulation of calcium flux in B
      cells.
AB  - Human B cells express two closely related immunoglobulin G receptors, FcRIIb1 and
      FcRIIb2, which differ by a 19 amino acid insertion in the cytoplasmic tail of
      FcRIIb1. The cytoplasmic tails of both isoforms contain a conserved sequence
      motif (AENTITYSLL) essential for mediating endocytosis via FcRIIb2. Truncation of
      this motif abolished endocytosis, while replacement of tyrosine (Tyr273) in
      FcRIIb2 by phenylalanine had no effect on the amount and kinetics of ligand
      uptake. Co-cross-linking of FcRIIb1 or FcRIIb2 with the antigen receptor on B
      cells led to an abortive calcium signal. Neither isoform interfered with the
      early intracellular calcium mobilization, but both prevented the opening of a
      plasma membrane calcium channel essential for a sustained elevated intracellular
      calcium level. Modulation of calcium channel activity is mediated by the same
      sequence motif essential for endocytosis but requires the presence of Tyr292 in
      FcRIIb1 and Tyr273 in FcRIIb2. Co-cross-linking of FcRIIb1 with surface IgG is
      associated with tyrosine phosphorylation of Tyr292, whereas Tyr272 in FcRIIb2 was
      not phosphorylated. Thus, FcRIIb phosphorylation is probably not directly
      involved in the modulation of the calcium signal but may be essential for further
      diversification of signals transduced via the coexpressed isoforms FcRIIb1 and
      FcRIIb2.

PMID- 7527038
TI  - Evaluation of the catalytic mechanism of recombinant human Csk (C-terminal Src
      kinase) using nucleotide analogs and viscosity effects.
AB  - Tyrosine kinases catalyze phosphoryl transfers from ATP to tyrosine residues in
      proteins. Despite their growing importance, their kinetic mechanism has remained
      largely unexplored. In this study, we have investigated the tyrosine kinase
      reaction catalyzed by purified human recombinant Csk (C-terminal Src kinase).
      Poly(Glu,Tyr) 4:1 was used as the tyrosine-containing substrate. Both ATP and
      poly(Glu,Tyr) were shown to be well behaved saturable substrates for recombinant
      Csk, with Km values that were in reasonable agreement with literature values
      reported for the non-recombinant enzyme and with kcat about 40 min-1. A
      sequential kinetic mechanism is suggested by a steady state kinetic analysis.
      Inhibitor studies with ADP and beta,gamma-imidoadenosine 5'-triphosphate were
      performed, and these results provided evidence against the possibility that
      ordered binding of peptide prior to ATP occurs. While a suitable competitive
      inhibitor of poly(Glu,Tyr) has not yet been identified, other evidence pointed to
      a rapid equilibrium random mechanism. Csk utilized adenosine 5'-O-(3
      thiotriphosphate) in place of ATP. The phosphorothioyl transfer occurred with a
      kcat about 15-20-fold lower than the ATP reaction but with similar Km values.
      Deuterium solvent isotope effects on kcat were small for both reactions in a pH
      independent range, consistent with the possibility that proton transfer is
      asymmetric in the reaction transition state. Using viscosity effects, ADP product
      release was suggested to be partially rate determining for catalysis in the
      standard ATP reaction. A comparison of the Csk kinetic mechanism with that of
      protein kinase A is discussed.

PMID- 7527039
TI  - The nucleic acid binding activity of nucleolar protein B23.1 resides in its
      carboxyl-terminal end.
AB  - Protein B23 is a major nucleolar phosphoprotein proposed to be a ribosome
      assembly factor. Protein B23 exists as two isoforms, B23.1 and B23.2, differing
      only in their carboxyl-terminal sequences. The interaction of recombinantly
      produced B23 isoforms with double-stranded DNA was studied using gel retardation
      and nitrocellulose filter disk assays. Protein B23.1 bound saturably to
      radiolabeled plasmid DNA. By competition assays protein B23.1 was also capable of
      binding RNA and single-stranded DNA. On the other hand, protein B23.2, the
      shorter of the two isoforms, was not capable of binding double-stranded DNA. The
      latter result suggested that the carboxyl-terminal end of B23.1 is essential for
      DNA binding activity. This was confirmed by partial digestion experiments using
      staphylococcal V8 protease which showed that a 5-kDa fragment, containing the
      carboxyl-terminal end of protein B23.1 retained DNA binding activity similar to
      that of the parent molecule. In contrast, a 19-kDa fragment from the amino
      terminal half of B23.1 did not bind DNA. The sequence of the carboxyl-terminal 68
      amino acids comprising the 5-kDa fragment showed little, if any, similarity to
      other proteins, suggesting that this segment contains a previously undiscovered
      nucleic acid binding motif.

PMID- 7527037
TI  - FKBP46, a novel Sf9 insect cell nuclear immunophilin that forms a protein-kinase
      complex.
AB  - Recently, we identified a 59-kDa nuclear phosphoprotein that is associated with a
      recombinant mouse FKBP-52 (Alnemri, E. S., Fernandes-Alnemri, T., Nelki, D. S.,
      Dudley, K., DuBois, G. C., and Litwack, G. (1993) Proc. Natl. Acad. Sci. U.S.A.
      90, 6839-6843). Here we describe the cloning, overexpression, and
      characterization of this protein from Spodoptera frugiperda insect cells (Sf9
      cells). The cloned cDNA codes for an acidic protein of 412 amino acids with
      distinct structural domains. Starting with the N terminus, the first 218 amino
      acids contain two highly acidic domains separated by a short basic domain.
      Following the second large acidic domain is another basic domain of 87 amino
      acids with significant sequence and structural homology to HMG1 and HMG2 DNA
      binding proteins. The two basic domains contain several nuclear targeting
      signals. The last 108 C-terminal amino acids contain a binding domain for
      immunosuppressive drugs FK506 and rapamycin, which makes this protein a new
      member of the immunophilin family. We provide evidence that the new immunophilin
      (FKBP46) is a DNA binding protein that can bind immunosuppressive drug FK506 and
      possesses peptidylprolyl isomerase activity. FKBP46 is localized in the nucleus
      and is associated with a nuclear kinase that specifically phosphorylates it in
      the presence of Mg2+ and ATP. Upon subsequent sequence analysis of the mouse
      FKBP52 cDNA used in our previous study, it was observed that a spermatid nuclear
      transition protein 2 (TP2) sequence is fused in frame with the C terminus of the
      recombinant FKBP52 probably as a result of a cloning artifact. We demonstrate
      that the FKBP46 does not form a complex with the FKBP52 but rather with the
      highly basic nuclear protein TP2. Our data suggest that interaction of FKBP46
      with TP2 is mediated by the N-terminal acidic domains of FKBP46. This implies
      that the acidic domains of FKBP46 are involved in protein-protein interaction
      between nuclear FKBP46 and other basic chromatin proteins.

PMID- 7527040
TI  - Isolation and characterization of MRF-1, a brain-derived DNA-binding protein with
      a capacity to regulate expression of myelin basic protein gene.
AB  - The 5'-flanking region of the myelin basic protein (MBP) contains several
      regulatory elements that differentially contribute to the cell type-specific
      transcription of MBP in cells derived from the central nervous system. The distal
      regulatory element, termed MB3, had previously been shown to have characteristics
      of a cell type-specific enhancer element and bind to multiple brain-derived
      nuclear proteins in vitro. We now report the isolation of a recombinant cDNA
      clone, named myelin regulatory factor-1 (MRF-1) from a mouse brain expression
      library that encodes a novel protein which interacts with the MB3 domain.
      Computer-assisted analysis of MRF-1 revealed substantial sequence homology in the
      central and the COOH-terminal regions of this protein with the previously
      identified splicing factor SC35. Cotransfection studies indicated that MRF-1
      increases transcription of the MBP promoter in glial cells and that this
      activation requires an intact MRF-1-binding site within the MB3 region. MRF-1
      cDNA hybridized to three RNA species 1.8, 2.5, and 3.0 kilobases which are
      expressed in all tissues analyzed. The gene encoding MRF-1 is located on the
      distal half of mouse chromosome 11 in a region where the human homolog would be
      predicted to reside on human chromosome 17.

PMID- 7527041
TI  - Potassium channel induction by the Ras/Raf signal transduction cascade.
AB  - p21ras plays a critical role in cell growth, differentiation, and oncogenic
      transformation. However, the final physiological effectors of p21ras-mediated
      signal transduction remain to be determined. We have used patch clamp
      electrophysiology, pharmacological agents, and transfection with specific Ras or
      Raf plasmids, to demonstrate that induction of a unique Ca(2+)-activated K+
      channel in murine fibroblast cell lines depends on p21ras and its immediate
      downstream target, the Raf kinase. The importance of this channel in mitogenic
      signaling is further indicated by its induction in nontransformed cells by
      epidermal growth factor and platelet-derived growth factor and the ability of K+
      channel blockers to inhibit cell proliferation. We suggest that this Ca(2+)
      activated K+ channel is one ultimate physiological target of p21ras-mediated
      signal transduction and that it may play a role in cell proliferation and ras
      transformation.

PMID- 7527043
TI  - Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine
      1148 of activated human epidermal growth factor receptors in intact cells.
AB  - The activation of receptor tyrosine kinases generates tyrosine-phosphorylated
      recognition motifs for the binding of signaling proteins containing Src homology
      2 domains. We determined the binding sites of Grb2/Ash, an Src homology 2 domain
      containing adaptor protein, within epidermal growth factor (EGF) receptors, using
      Chinese hamster ovary cells overexpressing human EGF receptor mutants in which
      one of the autophosphorylation sites was retained. In intact cells, the amount of
      Grb2/Ash coimmunoprecipitated with mutant receptors retaining tyrosines 992,
      1068, 1086, 1148, or 1173 was approximately 10, 85, 55, 50, or 20% of wild-type
      levels, respectively. The association of Grb2/Ash with in vitro
      autophosphorylated EGF receptor mutants was detectable in those retaining either
      tyrosines 1068 or 1086 but not in other mutants including those retaining
      tyrosine 1148. In peptide inhibition assay, phosphorylated peptides representing
      tyrosines 1068 and 1086 inhibited the binding of Grb2/Ash to in vitro
      autophosphorylated wild-type EGF receptors, whereas the other peptides
      representing tyrosines 992, 1148, and 1173 failed to inhibit the binding. Given
      that tyrosine 1148 of the activated EGF receptor is a major binding site of Shc
      (Okabayashi, Y., Kido, Y., Okutani, T., Sugimoto, Y., Sakaguchi, K., and Kasuga,
      M. (1994) J. Biol. Chem. 269, 18674-18678), these results indicate that tyrosines
      1068 and 1086 of activated human EGF receptors are direct high affinity binding
      sites of Grb2/Ash and that tyrosine 1148 is an indirect binding site through Shc
      in intact cells.

PMID- 7527042
TI  - Sequential activation of Raf-1 kinase, mitogen-activated protein (MAP) kinase
      kinase, MAP kinase, and S6 kinase by hyperosmolality in renal cells.
AB  - In the renal medulla during antidiuresis, the extracellular fluid becomes
      hyperosmotic. Madin-Darby canine kidney (MDCK) epithelial cells adapt in
      hyperosmotic conditions and serve as a useful tissue culture model for cellular
      responses to hyperosmolality. We demonstrate that hyperosmolality stimulates
      phospholipase C, Raf-1 kinase mitogen-activated protein (MAP) kinase kinase, MAP
      kinase, and S6 kinase activities and that it increases phosphorylation of Raf-1
      kinase, and p42 MAP kinase in MDCK cells. Stimulation of these kinases is
      osmolality-dependent (from 300 to 600 mosm/kg H2O). The time course of activation
      is sequential; the peak stimulation for Raf-1 kinase is at 5 min, at 10 min for
      MAP kinase kinase and MAP kinase, and at 20 min for S6 kinase. The activation of
      Raf-1 kinase and MAP kinase is inhibited by phorbol 12-myristate 13-acetate
      pretreatment in the presence of calphostin C or H-7. Tyrosine kinase inhibitors
      (genistein, herbimycin) do not significantly suppress hyperosmolality-induced MAP
      kinase activity. The increase of Ins-1,4,5-P3 levels by hyperosmolality suggests
      that activation of these kinases is mediated at least partially via activation of
      phospholipase C. Thus, hyperosmolality stimulates the serine/threonine kinases,
      Raf-1 kinase, MAP kinase kinase, MAP kinase, and S6 kinase, via predominantly
      protein kinase C-dependent, tyrosine kinase-independent pathways in MDCK cells.

PMID- 7527045
TI  - Attenuation of adenylate cyclase-induced increases in renal sodium excretion by
      the dopamine D-2 receptor agonist SK&F 89124.
AB  - 1. Although the existence of D-2 receptor binding sites in kidney has been
      identified, their functional significance in terms of influencing renal sodium
      excretion is not clear. In the present study we have examined the renal effects
      of a selective D-2 receptor agonist, SK&F 89124, in anaesthetized rats. 2.
      Intravenous infusion of SK&F 89124 (0.3, 1 and 3 micrograms kg-1 min-1
      respectively) produced dose-dependent decreases in mean arterial blood pressure,
      heart rate and renal blood flow without causing any significant changes in urine
      output, urinary sodium excretion, renal vascular resistance or glomerular
      filtration rate. The changes in blood pressure, heart rate and renal blood flow
      caused by SK&F 89124 were abolished by a selective D-2 receptor antagonist,
      domperidone (50 micrograms kg-1 i.v. bolus; 10 micrograms kg-1 min-1). 3;
      Treatment with 3-isobutyl-1-methylxanthine (IBMX, 1 mg kg-1 bolus i.v.) or
      forskolin (200 micrograms kg-1 bolus i.v.) produced increases in heart rate,
      urine output and urinary sodium excretion, but there was no change in mean blood
      pressure. The natriuretic and diuretic response, but not tachycardiac response to
      IBMX or forskolin, was attenuated by SK&F 89124 (0.3 micrograms kg-1 min-1). 4.
      These results suggest that the selective D-2 receptor agonist, SK&F 89124,
      produced a significant decrease in blood pressure and heart rate via
      prejunctional D-2 receptor-mediated inhibition of noradrenaline release from
      postganglionic sympathetic nerve terminals. Although activation of renal tubular
      D-2 receptors had no significant effect on renal excretory function under basal
      conditions, it is likely that these receptors may exert an opposing effect on
      cAMP-mediated increases in renal sodium and water excretion.

PMID- 7527044
TI  - Effect of sympathetic denervation on the relaxing responses of rabbit arterial
      smooth muscle.
AB  - 1. The present study reports on the influence of chemical denervation by 6
      hydroxydopamine (6-OHDA) on the relaxing responses to carbachol, sodium
      nitroprusside, zaprinast, adenosine, forskolin and 3-isobutyl-1-methylxanthine
      (IBMX) of ring preparations of rabbit renal and femoral arteries. 2. Carbachol
      was found to induce a complete abolition of the tone induced by 5
      hydroxytryptamine (0.1-1.0 microM), both in the renal and the femoral arteries.
      The profile of the carbachol-induced relaxation in both the renal and femoral
      arteries obtained from 6-OHDA-treated rabbits was similar to that observed in
      control animals; relaxing responses obtained with some of the concentrations of
      carbachol were, however, found to be greater (P < 0.01) in denervated arteries.
      Sodium nitroprusside was also found to be an effective relaxant agent in both
      renal and femoral arteries, though more potent in the former but was unaffected
      by denervation. Zaprinast relaxed both renal and femoral artery ring
      preparations, and again, no significant difference was observed between control
      and denervated animals. 3. The cyclic AMP-mediated relaxing responses to
      adenosine, forskolin and IBMX were found to be similar in renal and femoral
      arteries of control arteries, producing almost complete abolition of pre-existing
      tone. The adenosine- and IBMX-induced relaxing responses in renal and femoral
      arteries were found to be similar in control and denervated animals. However, the
      concentration-response curve to forskolin was shifted to the left by 2.5 and 1.5
      log units in preparations of renal and femoral arteries of denervated rabbits,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527047
TI  - Redistribution of cytoplasmic components during germinal vesicle breakdown in
      starfish oocytes.
AB  - The starfish oocyte is relatively clear optically, and its nucleus, termed the
      germinal vesicle, is large. These characteristics allowed studies by confocal
      microscopy of germinal vesicle breakdown during maturation in living oocytes.
      Three fluorescent probes for cytoplasmic components were used: fluorescein 70 kDa
      dextran, which does not cross the nuclear pore of immature oocytes and probably
      behaves in the same way as soluble cytosolic proteins, YOYO-1, which was used to
      localize ribosomes, and DiI which labels the nuclear envelope and endoplasmic
      reticulum. The first change observable by transmitted light microscopy during
      maturation is a wrinkling of the germinal vesicle envelope. Several minutes
      before the wrinkling, the 70 kDa dextran began to enter the germinal vesicle; the
      ribosomes did not enter during this period. The dextran is likely to be passing
      through nuclear pores whose size limit has increased but which still exclude
      ribosomes. At the time of the wrinkling of the germinal vesicle envelope, both 70
      kDa dextran and ribosomes entered as a massive wave. The characteristics of this
      entry indicate that the permeability barrier of the nuclear envelope bilayer has
      been disrupted. The disruption of the permeability barrier occurred in a local
      region rather than around the entire periphery. Also, the disruption was observed
      more often on the animal pole side of the germinal vesicle (26/34 oocytes). The
      endoplasmic reticulum entered the nuclear region more slowly. Cytochalasin B
      inhibited this movement and also inhibited characteristic endoplasmic reticulum
      movements seen at high magnification. The effects of cytochalasin indicate that
      mixing of endoplasmic reticulum with nuclear space is an active process involving
      actin filaments.

PMID- 7527046
TI  - In vivo and electron microscopic studies of rat liver after intravenous injection
      of polyamino acid microspheres.
AB  - In vivo and electron microscopy were used to study the hepatocellular responses
      of rat livers to intravenously injected polymeric microspheres. Two microsphere
      preparations with different surface characteristics and degradability were used
      in this study. In vivo microscopy revealed that both poly(benzyl L-glutamate)
      (PBLG) and poly(hydroxypropyl L-glutamine) (PHPG) microspheres caused disturbance
      in the microcirculation of rat liver up to 2 months after injection. The observed
      changes included stagnant flow and adherence of white blood cells to the
      endothelial lining of venules an sinusoids. Kupffer cell (KC) activation
      following phagocytosis of microspheres was evidenced by the enlargement of KCs
      and increased number of KCs taking up fluorescent latex particles. Electron
      microscopy of rat livers revealed a wide range of hepatocellular injury
      associated with the administration of PBLG and PHPG microspheres. These results
      indicate that a small amount of remaining microspheres is sufficient to induce
      continuous disturbance to hepatic microcirculation and that particulate drug
      carriers should be designed to be rapidly degraded so that the return to normal
      liver function is possible.

PMID- 7527048
TI  - Cell cycle-specific induction of an 89 kDa serine/threonine protein kinase
      activity in Trypanosoma brucei.
AB  - The cell cycle compartmentalization of specific activities of the protozoan
      parasite Trypanosoma brucei has remained unexplored due to the lack of a cell
      synchronization protocol. We report here that stationary phase cells stimulated
      to enter the cell cycle showed significant synchrony through the first cycle. The
      pattern of tyrosine phosphorylated proteins, known to undergo alterations during
      trypanosome development, showed only moderate changes as quiescent cells entered
      the cycle, particularly an increase in a 77 kDa species. However, the activity of
      an 89 kDa protein kinase (SPK89), previously demonstrated to be restricted to the
      proliferative stages of the parasite's life cycle, markedly increased as the
      population entered S phase. Cell sorting experiments demonstrated that SPK89
      activity was highest in S phase cells and moderate in G2/M cells. The entry into
      S phase and increased SPK89 activity did not depend on serum factors but required
      protein synthesis for a discrete period after stimulation. Various modulators of
      protein phosphorylation were tested to determine their effects on progression to
      S and SPK89 activity. Only staurosporine and genistein were effective. However,
      both of these compounds inhibited virtually all protein phosphorylation and
      protein synthesis in the parasites. Thus these drugs cannot be used as specific
      protein kinase inhibitors in trypanosomes.

PMID- 7527049
TI  - Mitotic arrest with anti-microtubule agents or okadaic acid is associated with
      increased glycoprotein terminal GlcNAc's.
AB  - The two major intermediate filament glycoproteins in human simple epithelia are
      keratins 8 and 18 (K8/18). A dramatic increase in terminal N-acetylglucosamine
      (GlcNAc) residues in K8/18 was previously noted after arresting cells in G2/M
      using anti-microtubule agents. Here we use in vitro galactosylation to show that
      increased terminal GlcNAc's is a general phenomenon that occurs in glycoproteins
      isolated from nuclear and plasma membrane fractions after cells are arrested in
      mitosis using colcemid, nocodazole, or okadaic acid. All three agents also
      resulted in a hyperphosphorylated form of K8 as determined by phosphatase
      treatment and tryptic phosphopeptide mapping. The altered glycosylation was found
      to be independent of microtubule disassembly, and was not directly related to the
      G2/M phase of the cell cycle after aphidicolin synchronization. Staurosporine (1
      microM) inhibited K8/18 phosphorylation in okadaic acid- or nocodazole-treated
      cells, and inhibited the increase in K8/18 glycosylation without inhibiting the
      increase in terminal GlcNAc's of membrane-associated glycoproteins. In contrast,
      brefeldin A resulted in a dramatic increase in terminal GlcNAc's of membrane
      associated but not intermediate filament proteins. Golgi complex-related staining
      using anti-beta-COP antibody showed significant fragmentation under conditions
      associated with altered membrane protein glycosylation. Our results suggest that
      Golgi disruption may be involved in the observed increase in terminal GlcNAc's of
      membrane but not intermediate filament glycoproteins. The mechanism of increased
      glycoprotein terminal GlcNAc's in association with mitotic arrest appears to be
      distinct for intermediate filaments and membrane-associated proteins, and in the
      case of intermediate filament proteins, phosphorylation may play an important
      role. Some of the effects of agents that induce mitotic arrest may be mediated by
      glycosylation changes.

PMID- 7527051
TI  - Salmonella typhimurium induces selective aggregation and internalization of host
      cell surface proteins during invasion of epithelial cells.
AB  - Salmonella interact with eucaryotic membranes to trigger internalization into non
      phagocytic cells. In this study we examined the distribution of host plasma
      membrane proteins during S. typhimurium invasion of epithelial cells. Entry of S.
      typhimurium into HeLa epithelial cells produced extensive aggregation of cell
      surface class I MHC heavy chain, beta 2-microglobulin, fibronectin-receptor
      (alpha 5 beta 1 integrin), and hyaluronate receptor (CD-44). Other cell surface
      proteins such as transferrin-receptor or Thy-1 were aggregated by S. typhimurium
      to a much lesser extent. Capping of these plasma membrane proteins was observed
      in membrane ruffles localized to invading S. typhimurium and in the area
      surrounding these structures. In contrast, membrane ruffling induced by epidermal
      growth factor only produced minor aggregations of surface proteins, localized
      exclusively in the membrane ruffle. This result suggests that extensive
      redistribution of these proteins requires a signal related to bacterial invasion.
      This bacteria-induced process was associated with rearrangement of polymerized
      actin but not microtubules, since preincubation of epithelial cells with
      cytochalasin D blocked aggregation of these proteins while nocodazole treatment
      did not. Of the host surface proteins aggregated by S. typhimurium, only class I
      MHC heavy chain was predominantly present in the bacteria-containing vacuoles. No
      extensive aggregation of host plasma membrane proteins was detected when HeLa
      epithelial cells were infected with invasive bacteria that do not induce membrane
      ruffling, including Yersinia enterocolitica, a bacterium that triggers
      internalization via binding to beta 1 integrin, and a S. typhimurium invasion
      mutant that utilizes the Yersinia-internalization route. In contrast to the
      situation with S. typhimurium, class I MHC heavy chain was not selectively
      internalized into vacuoles containing these other bacteria. Extensive aggregation
      of host plasma membrane proteins was also not observed when other S. typhimurium
      mutants that are defective for invasion were used. The amount of internalized
      host plasma membrane proteins in the bacteria-containing vacuoles decreased over
      time with all invasive bacteria examined, indicating that modification of the
      composition of these vacuoles occurs. Therefore, our data show that S.
      typhimurium induces selective aggregation and internalization of host plasma
      membrane proteins, processes associated with the specific invasion strategy used
      by this bacterium to enter into epithelial cells.

PMID- 7527050
TI  - Function of type I and type II keratin head domains: their role in dimer,
      tetramer and filament formation.
AB  - To examine the role of the keratin head region and its subdomains in filament
      assembly we constructed several deletion mutants of type I and type II keratins
      and analysed their in vitro IF forming capacity. The delta K8 (1-74) and delta
      K18 (1-56), mutants formed only soluble oligomers, predominantly tetramers with
      their heterotypic partners. K8 mutants that retained either the entire (delta K8
      (1-64)) or nearly the entire (delta K8 (1-66)) H1 subdomain formed some short and
      irregular IF-like structures with K18. However, filaments never reached the
      normal length and more protofilamentous material was observed. Analysis of the
      soluble complexes in 2 M guanidine-HCl indicated that tetramer formation was
      impaired in the truncated molecules. The length of the deletion correlated with
      the degree of tetramer destabilization. These results suggest that the head
      domain--specifically the H1 subdomain of type II keratins-plays a direct role in
      IF assembly. Its functions include a stabilization of the tetramer molecule,
      suggesting a role in directing the alignment of dimers as well as in elongation.
      We also analysed whether both head domains are required or if either type I or
      type II head domains alone are sufficient for IF formation. Hybrid molecules
      carrying their partner keratins head domains (K18 (8 head) and K8 (18 head)) were
      combined with their wild-type partners and tested for IF-forming ability. Both
      combinations formed filaments distinct from normal IF. The effect of the
      'replaced' head domains was not compensated when both hybrid molecules were
      combined. Taken together, the results indicate that complete removal of the head
      domains of either K8 or K18 arrested IF assembly at the state of soluble
      oligomers. Replacement of the head domains by head domains of the complementary
      partner partly compensated for the effect. However, regular IF formation could
      not take place when either the head domain was missing or it was replaced by the
      partner's keratin head.

PMID- 7527053
TI  - Changes in annexin I and II levels during the postnatal development of rat
      pancreatic islets.
AB  - The expression patterns and the dynamic changes in content of both annexin I and
      annexin II in the rat pancreatic islets during postnatal development were
      investigated by both western blot analysis and immunohistochemistry.
      Immunohistochemical methods clearly demonstrated the presence of annexins I and
      II exclusively in pancreatic islets, while exocrine tissues were not stained by
      anti-annexin antibodies. Pancreatic islets were diffusely stained with no
      specific differences in distribution between different cell types. The expression
      of annexin I in pancreatic islets gradually increased with postnatal development.
      A developmental study of annexins I and II by western blot analysis essentially
      supported the results obtained by immunohistochemistry. In addition, the
      increasing expression of two protein tyrosine kinases, epidermal growth factor
      receptor/kinase and pp60src, which phosphorylate annexin I and annexin II,
      respectively, and of protein kinase C, which phosphorylates both proteins, was
      also shown during postnatal development in rat pancreatic islets. Thus, a
      relationship between the expression of annexins I and II and the maturation of
      islet cell function is suggested.

PMID- 7527054
TI  - Identification of a key integrin-binding sequence in VCAM-1 homologous to the LDV
      active site in fibronectin.
AB  - The integrin adhesion receptor alpha 4 beta 1 binds two ligands, the
      extracellular matrix glycoprotein fibronectin and the immunoglobulin superfamily
      member VCAM-1. Ligand-binding sites are contained with the HepII/IIICS domain of
      fibronectin, and within the homologous immunoglobulin domains 1 and 4 of VCAM-1.
      Previous studies have shown that the binding of each ligand to alpha 4 beta 1 is
      mutually exclusive, suggesting that they may employ similar mechanisms to bind
      receptor. Fibronectin contains at least three distinct peptide sequences that are
      active sites for alpha 4 beta 1 binding, two homologous sequences Leu-Asp-Val-Pro
      (LDVP) and Ile-Asp-Ala-Pro (IDAP), and a third related to Arg-Gly-Asp (RGD).
      Using a combination of site-directed mutagenesis and synthetic peptide approaches
      in conjunction with VCAM-1-dependent cell adhesion assays, we now report the
      identification of a key alpha 4 beta 1-binding sequence in both domains 1 and 4
      of VCAM-1 as the tetrapeptide Ile-Asp-Ser-Pro (IDSP). Mutagenesis studies also
      suggest that an additional sequence in domain 1, KLEK, participates in receptor
      binding. Since IDSP is homologous to the LDVP and IDAP fibronectin peptides, this
      therefore provides a molecular explanation for the promiscuity of ligand binding
      by alpha 4 beta 1 and has implications for the design of synthetic VCAM-1
      antagonists. The extrapolation of these findings to other integrin-binding
      immunoglobulin ligands is also discussed.

PMID- 7527052
TI  - The RhoA-dependent assembly of focal adhesions in Swiss 3T3 cells is associated
      with increased tyrosine phosphorylation and the recruitment of both pp125FAK and
      protein kinase C-delta to focal adhesions.
AB  - Mouse Swiss 3T3 fibroblasts cultured in serum-free medium lose their actin stress
      fibres and vinculin-containing focal adhesions, a process that can be reversed by
      the addition of serum, lysophosphatidic acid (LPA) or bombesin, and is mediated
      by rhoA (A. J. Ridley and A. Hall (1992) Cell 70, 389-399). We have shown that
      the addition of serum to these cells induces the recruitment of the cytoskeletal
      proteins talin, vinculin and paxillin, and the protein kinases pp125FAK and PKC
      delta, to newly formed focal adhesions, and that alpha-actinin is distributed
      along the actin stress fibres associated with these structures. The newly formed
      focal adhesions stained heavily with an antibody to phosphotyrosine. A similar
      response was elicited by 100 ng/ml LPA. The effect of serum was rapid, with focal
      staining for paxillin largely restricted to cell margins seen within 2 minutes of
      serum addition, and preceding the assembly of actin filaments. Phosphotyrosine
      staining differed in that it was predominantly punctate and was widely
      distributed throughout the cell. By 5 minutes, the paxillin and phosphotyrosine
      staining was concentrated at the ends of actin filaments largely at the cell
      margins. The structures stained ranged from circular to oval, but by 10 minutes
      they more closely resembled the elongated focal adhesions found in cultured
      fibroblasts. Within 10 minutes, the addition of serum or LPA induced a marked
      increase in the levels of pp125FAK and paxillin immune-precipitated by an anti
      phosphotyrosine antibody. The results suggest that both pp125FAK and paxillin
      undergo changes in tyrosine phosphorylation upon activation of rhoA, and that
      these changes are associated with the assembly of focal adhesions and actin
      stress fibres. The observation that formation of focal adhesions can be induced
      by the tyrosine phosphatase inhibitor vanadyl hydroperoxide is consistent with
      the direct involvement of tyrosine phosphorylation in the assembly process. The
      localisation of PKC-delta to newly formed focal adhesions suggests that
      serine/threonine phosphorylation may also be important in this regard.

PMID- 7527056
TI  - Movement of axoplasmic organelles on actin filaments assembled on acrosomal
      processes: evidence for a barbed-end-directed organelle motor.
AB  - The directionality of the actin-dependent motors on squid axoplasmic organelles
      was determined using actin filaments assembled on the barbed ends of acrosomal
      processes. Acrosomal processes were isolated from Limulus polyphemus sperm and
      incubated in monomeric actin under conditions that promoted barbed end assembly
      only. Newly assembled actin was stabilized and stained with rhodamine-phalloidin
      and the presence of filaments at the barbed ends of the acrosomal processes was
      verified by fluorescence microscopy and negative contrast electron microscopy.
      Axoplasmic organelles that dissociated from extruded axoplasm were observed by
      video microscopy to move along the newly assembled actin filaments at an average
      velocity of 1.1 +/- 0.3 microns/second. All organelles moved in the direction
      away from the acrosomal fragment and towards the tip of the actin filaments.
      Therefore, the actin-dependent organelle motor on axoplasmic organelles is a
      barbed-end-directed motor like other myosins analyzed. These findings support the
      conclusions that axoplasmic organelles are driven by a myosin-like motor along
      actin filaments and that these filaments as well as microtubules function in fast
      axonal transport.

PMID- 7527055
TI  - Band 6 protein, a major constituent of desmosomes from stratified epithelia, is a
      novel member of the armadillo multigene family.
AB  - Desmosomes are intercellular adhering junctions characteristic of epithelial
      cells. Several constitutive proteins--desmoplakin, plakoglobin and the
      transmembrane glycoproteins desmoglein and desmocollin--have been identified as
      fundamental constituents of desmosomes in all tissues. A number of additional and
      cell type-specific constituents also contribute to desmosomal plaque formation.
      Among these proteins is the band 6 polypeptide (B6P). This positively charged,
      non-glycosylated protein is a major constituent of the plaque in stratified and
      complex glandular epithelia. Using an overlay assay we show that purified
      keratins bind in vitro to B6P. Thus B6P may play a role in ordering intermediate
      filament networks of adjacent epithelial cells. To characterize the structure of
      B6P in the desmosome we have isolated cDNA clones representing the entire coding
      sequence. The predicted amino acid sequence of human B6P shows strong sequence
      homology with a murine p120 protein, which is a substrate of protein tyrosine
      kinase receptors and of p60v-src. P120 and B6P show amino-terminal domains
      differing distinctly in length and sequence. These are followed in both proteins
      by 460 residues that display a series of imperfect repeats corresponding to the
      repeats in the cadherin binding proteins armadillo, plakoglobin and beta-catenin.
      Over this repeat region B6P and p120 share 33% sequence identity (54%
      similarity). These sequence characteristics define B6P as a novel member of the
      armadillo multigene family and raise the question of whether the structural
      proteins B6P, plakoglobin, beta-catenin and armadillo share some function. Since
      armadillo, plakoglobin, beta-catenin and p120 seem involved in signal
      transduction this may also hold for B6P. The amino-terminal region of B6P
      (residues 1 to 263) shows no significant homology to any known protein sequence.
      It may therefore be involved in unique functions of B6P.

PMID- 7527057
TI  - Developmental regulation of polyglutamylated alpha- and beta-tubulin in mouse
      brain neurons.
AB  - Polyglutamylation is an important posttranslational modification of tubulin that
      is very active in nerve cells, where it accounts for the main factor responsible
      for tubulin heterogeneity. In the present work, we have analyzed quantitative and
      qualitative changes in glutamylated alpha- and beta-tubulin occurring during
      neuronal differentiation in culture. Glutamylated alpha- and beta-tubulin both
      markedly accumulate during this process with a time course remarkably similar to
      that observed in vivo during brain development. However, the characteristics of
      the glutamylation of the two subunits are not exactly the same. Glutamylated
      alpha-tubulin is already abundant in very young neurons and displays, at this
      stage, a wide range of its degree of glutamylation (1 to 6 glutamyl units present
      in the lateral polyglutamyl chain), which remains unchanged during the entire
      period of the culture. Glutamylated beta-tubulin is present at very low levels in
      young neurons and its accumulation during differentiation is accompanied by a
      progressive increase in its degree of glutamylation from 2 to 6 glutamyl units.
      Posttranslational incorporation of [3H]glutamate into alpha- and beta-tubulin
      decreases during differentiation, as well as the rate of the reverse
      deglutamylation reaction, suggesting that accumulation of glutamylated tubulin is
      accompanied by a decrease in the turnover of glutamyl units onto tubulin.
      Neuronal differentiation is also accompanied by an increase of other
      posttranslationally modified forms of tubulin, including acetylated and non
      tyrosinatable alpha-tubulin, which can occur in combination with
      polyglutamylation and contributes to increase the complexity of tubulin in mature
      neurons.

PMID- 7527058
TI  - Tenascin-R (J1 160/180 inhibits fibronectin-mediated cell adhesion--functional
      relatedness to tenascin-C.
AB  - Cell adhesion and neurite outgrowth on fibronectin is a multistep process
      modulated by different extra- and intracellular signals. Fibronectin-mediated
      cell attachment and spreading can be affected in a negative way by tenascin-C, an
      extracellular matrix glycoprotein expressed in a temporally and spacially
      restricted manner during early morphogenesis. Tenascin-R (J1-160/180), consisting
      of two major isoforms of 160 kDa (tenascin-R 160) and 180 kDa (tenascin-R 180) in
      mammals, is an extracellular matrix glycoprotein of the central nervous system
      that shares high structural homologies with tenascin-C. Here we show that in
      relation to fibronectin-mediated adhesion, the two extracellular matrix molecules
      are also functionally closely related. When offered as mixed substrata with other
      extracellular matrix molecules, the two tenascin-R isoforms and tenascin-C
      derived from mouse brain selectively inhibit fibronectin-dependent cell adhesion
      and neurite outgrowth, and affect cell morphology of different mesenchymal and
      neural cells. This effect is partially due to interactions at the substrate level
      that result in a steric hindrance and/or conformational change of the cell
      binding sites of the fibronectin molecule. In addition, tenascin-R 180 and
      tenascin-C interact with cells by an RGD- and beta 1 integrin-independent
      mechanism, leading to cell rounding and detachment from such substrata. The
      expression of tenascin-R and tenascin-C in the nervous system at times and
      locations where fibronectin-mediated cellular processes take place may be related
      to the role of inhibitory signals in the extracellular matrix in the regulation
      of cell migration and differentiation in general.

PMID- 7527059
TI  - Development of a spontaneous permanent cell line of rabbit corneal epithelial
      cells that undergoes sequential stages of differentiation in cell culture.
AB  - Established epithelial cell lines that retain their differentiation potential and
      growth regulatory characteristics can provide valuable tools for studying gene
      regulation, extracellular matrix synthesis or growth factor response. They are
      also useful for drug development and toxicity testing. Experiments were therefore
      carried out to optimize culture conditions for the long-term, serial transfer of
      corneal epithelial cells in the presence of 3T3 feeder layers; and to establish a
      permanent cell line. In such experiments, rabbit corneal epithelial cells were
      seeded at low inoculation densities, and transferred every 5 days. After 80
      population doublings, an epithelial cell line, RCE1, emerged. The cell line is
      heteroploid, with an average population doubling time of 15.5 hours (vs 18 hours
      for primary cultures). When RCE1 cells reached confluence, they stratified to
      form a three- to five-layered epithelium and expressed the differentiation
      related keratin pair K3/K12 as shown by immunoblot and immunostaining.
      Biosynthetic labeling of proliferating, confluent and stratified cultures further
      showed that RCE1 cells expressed keratin pairs K5/K14, K6/K16 and K3/K12, thus
      mimicking faithfully the stage-dependent differentiation of primary cultures of
      rabbit corneal keratinocytes. The results demonstrated that RCE1 cells provide a
      useful model for studying corneal cell growth and differentiation.

PMID- 7527060
TI  - Compartmentation of NADPH-diaphorase activity in the mouse cerebellar cortex.
AB  - The mammalian cerebellum is built around an array of parasagittal bands of
      Purkinje cells that can be demonstrated by immunocytochemical staining for the
      differentiation antigen zebrin II. Climbing and mossy fiber afferents also
      terminate in bands, and the afferent terminal fields and the Purkinje cell bands
      are aligned. The convergence of mossy and climbing fiber pathways onto the
      Purkinje cells, which are the sole output of the cerebellar cortex, is a
      characteristic feature of cerebellar circuitry. Previous studies showed that when
      both afferent pathways are activated synchronously there develops a long-term
      depression of synaptic efficacy at the parallel fiber-Purkinje cell synapse. Two
      second messenger pathways mediate long-term depression: one involves
      diacylglycerol and protein kinase C, and the other involves nitric oxide that is
      generated by a nitric oxide synthase. We have studied the distribution of nitric
      oxide synthase in the adult mouse cerebellum by using nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase histochemistry. NADPH-diaphorase
      activity is found mainly in the granule and basket cells. Within the granular
      layer NADPH-diaphorase activity is expressed nonuniformly by patches of granular
      cells and synaptic glomeruli. The patches are seen in all lobules, are
      reproducible from individual to individual, and are topographically ordered with
      respect to the Purkinje cell compartments as revealed by using anti-zebrin II
      immunocytochemistry. These data imply that nitric oxide-dependent, long-term
      depression may only involve a subset of mossy fiber/granule cell projections, and
      that one role for nitric oxide may be to refine cerebellar receptive fields.

PMID- 7527061
TI  - Distribution of neuropeptide FF in porcine spinal cord in comparison with other
      neuropeptides and serotonin.
AB  - A large number of neurotransmitters and neuropeptides are concentrated in the
      dorsal horn of the spinal cord, where they interact in a complex manner and
      modulate sensory mechanisms. Most studies are carried out in the rat, and little
      is known of other species. It is relevant to study mammals with a more complex
      central nervous system, because pain mechanisms are central in both human and
      veterinary medicine. Immunoreactivity for neuropeptide FF, an amidated
      octapeptide originally isolated from bovine brain, was found immunocytochemically
      at all levels of porcine spinal cord. In contrast to other species studied so
      far, the peptide immunoreactivity in porcine spinal cord was confined to the
      intermediolateral gray matter, especially to the intermediolateral cell column
      and lamina X of the gray matter. This distribution was remarkably different from
      that of substance P, proenkephalin A-derived peptides, thyrotropin-releasing
      hormone, serotonin, and neuropeptide Y. Pharmacologic administration of
      neuropeptide FF alters behavior in assays for analgesia. The distribution of
      neuropeptide FF immunoreactivity as revealed by this study suggests that there
      may be marked species differences in the distribution and function of the
      peptide.

PMID- 7527062
TI  - Retinogeniculate projection fibers in the monkey optic chiasm: a demonstration of
      the fiber arrangement by means of wheat germ agglutinin conjugated to horseradish
      peroxidase.
AB  - The fiber arrangement of the retinogeniculate pathway was investigated in the
      chiasm of Japanese monkeys (Macaca fuscata) by an iontophoretic injection of
      wheat germ agglutinin conjugated to horseradish peroxidase into the lateral
      geniculate nucleus (LGN). It has been claimed that there is a distinct retinotopy
      in the monkey chiasm, despite lack of any clear anatomical evidence. However, the
      present data indicate a rather gross retinotopy or almost no discernible
      retinotopy. Fibers from the foveal-to-peripheral axis of the temporal retina show
      substantially no retinotopy owing to a marked overlap of fibers in the
      anterolateral and the posterocentral parts of the ipsilateral hemichiasm. In
      contrast, the foveal-to-peripheral axis of the nasal retina is re-formed in a
      gross dorsoventral order in the chiasm. That is, nasal foveal-parafoveal fibers
      which arise from small cells (which are P beta mode) pass in the dorsal part of
      the chiasm adjacent to the brain. They widely overlap nasal perifoveal fibers
      which cross the chiasm more ventrally with very little contact with the brain.
      The nasal perifoveal fibers also widely overlap nasal peripheral fibers which
      cross the chiasm more ventrally. Furthermore, the nasal peripheral fibers overlap
      nasal far peripheral fibers which arise from large cells (including many of the P
      alpha mode) which run near the pial surface. Fibers from the dorsal and ventral
      nasal retina cross the midline of the posterior and anterior parts of the chiasm,
      respectively, and are finally positioned in the medioventral and ventrocentral
      parts in the tract. Consequently, the dorsoventral retinal axis is re-formed
      posteroanteriorly in the midline of the chiasm and in a roughly mediolateral
      direction in the tract. Furthermore, the present study shows that the nasal and
      temporal retinal fibers coming from the same eye are acutely segregated in the
      prechiasmal region and the anterior part of the hemichiasm.

PMID- 7527063
TI  - The Thomsen-Friedenreich antigen-related carbohydrate antigens in human gastric
      intestinal metaplasia and cancer.
AB  - The Thomsen-Friedenreich antigen (T) is the core disaccharide of O-glycosylated
      complex carbohydrates and is presumed to be a cancer-associated carbohydrate
      antigen. However, we recently found that the expression of alpha-T and alpha 1-2
      fucosyl alpha-T in the gastric surface epithelia was regulated allogeneically. In
      the present study we addressed their changes in gastric differentiation
      disorders. Expression of the T-related antigens was studied histochemically with
      monoclonal antibody MBrl and peanut agglutinin in 22 normal, 14 metaplastic, and
      54 cancerous tissues. The sialylated antigens were detected after neuraminidase
      digestion. Gastric mucins were purified and examined to determine whether they
      were the carrier molecules of T. Expression of the normal antigens was decreased
      or not detected in about 80% of both disorders. Neosialylation of the T-related
      antigens was observed in the goblet cells of all metaplastic tissues. The
      absorptive cells did not express any T-related antigens. In gastric cancers,
      blocked synthesis, i.e., precursor accumulation or totally negative expression,
      was observed in approximately 66% and neosialylation in approximately 40%. The T
      related antigens were carried by mucins. We conclude that blocked synthesis of
      the T-related antigens was found in a cancer-specific manner. Neosialylation was
      invariably associated with intestinal metaplasia and occasionally with cancer.

PMID- 7527065
TI  - EM study on terminals labelled by phaseolus vulgaris lectin in ectostriatum
      periphericum and neostriatum intermedium.
AB  - The terminals of rotundal fibers labelled with Phaseolus Lectin anterograde
      tracer were studied in ectostriatum periphericum and neostriatum intermedium
      laterale with EM. These terminals belong to the fibers which cross the
      ectostriatum centrale before they enter the ectostriatum periphericum and
      neostriatum intermedium laterale. These terminals establish synapses with
      dendrites, spines and also with GABA immunogold stained somata. The EM results
      prove the connections of ectostriatum periphericum and neostriatum intermedium
      laterale with the visual system.

PMID- 7527066
TI  - Laminar distribution and morphology of NADPH-diaphorase containing neurons in the
      optic tectum of the pigeon.
AB  - The laminar distribution and morphology of nicotinamide adenine dinucleotide
      phosphate diaphorase (NADPH-d) containing neurons is studied in the optic tectum
      (OT) of the pigeon. NADPH-d positive cells are arranged in three bands: the first
      band, in the stratum griseum et fibrosum superficiale, sublayer II a, is formed
      by small marginal and horizontal neurons; the second band is broad and extends
      throughout layers II i-j and III (stratum griseum centrale); the third band lies
      around the tectal ventricle, and consists of neurons in the stratum griseum
      profundum (SGP) and tanycytes. A comparison with Golgi-impregnated sections
      suggests that most NADPH-d positive cells in the OT have local or intratectal
      axons, while the large efferent neurons in layers IIj and III are NADPH-d
      negative. Similarities and differences between NADPH-d containing neurons in the
      avian OT and the mammalian superior colliculus are discussed. The processes of
      NADPH-d positive neurons in the SGP and of the tanycytes of the tectal ventricle
      form dense fascicles traversing the stratum album centrale. They surround and
      contact the radial blood vessels that originate in the SGP. We discuss the
      possibility that NADPH-d, or nitric oxide synthase, plays a role in the
      regulation of local blood flow in the deep tectal layers.

PMID- 7527064
TI  - Primary trigeminal afferent neuron of the cat: II. Neuropeptide- and serotonin
      like immunoreactivity.
AB  - The distribution of several peptides and serotonin in the cat vibrissa primary
      afferents from the Merkel cell-axon complexes to their central projections in the
      principal trigeminal sensory nucleus was examined by peroxidase-antiperoxidase
      immunocytochemical technique. In the trigeminal ganglia, two populations of
      primary sensory neurons, containing immunoreactive material were identified: a
      few substance P-, bombesin-, somatostatin-, cholecystokinin-, and vasoactive
      intestinal polypeptide-like immunoreactive ganglion cells with small and medium
      sized somata, and many large non-labelled trigeminal neurons that were surrounded
      by substance P-, somatostatin-, cholecystokinin-, vasoactive intestinal
      polypeptide- and serotonin-positive pericellular baskets. Substance P-, bombesin-
      and vasoactive intestinal polypeptide-like immunoreactive substances were found
      in the basal side of Merkel cells from sinus hair follicles of the cat, whereas
      the associated axons were immunonegative. In the principal trigeminal sensory
      nucleus, cell bodies and fibres, containing substance P and bombesin were
      observed in both subdivisions. In addition, only nerve fibres and terminals
      showed somatostatin-, cholecystokinin-, vasoactive intestinal polypeptide- and
      serotonin-like immunoreactivity. The present results provide direct evidence that
      an ascending peptidergic system exist and that only substance P and, less likely,
      bombesin may be primary afferent neuroregulator(s) for the mechanosensory
      information in the cat trigeminal system.

PMID- 7527067
TI  - Cell adhesion to proteins separated by lithium dodecyl sulfate-polyacrylamide gel
      electrophoresis and blotted onto a polyvinylidene difluoride membrane: a new cell
      blotting technique.
AB  - Cell blotting, although conceptually simple, has failed to achieve wide practical
      application. Described here is a new cell-blotting technique which involves cell
      adhesion to protein bands after separation by lithium dodecyl sulfate
      polyacrylamide gel electrophoresis (LDS-PAGE) and blotting onto polyvinylidene
      difluoride (PVDF) membrane at 4 degrees C. Cell bands adherent on PVDF are
      detected using hematoxylin, or propidium iodide (PI) staining followed by viewing
      under ultraviolet (UV) light. The technique allows quick microscopic
      visualization of adherent cells composing the bands, without requiring clearing
      of the membrane. Representative cell adhesion proteins from different sources,
      i.e., plant lectins (e.g., phytohemagglutinin, PHA; concanavalin A, ConA; and
      wheat germ agglutinin, WGA); extracellular matrix (ECM) proteins; and integral
      membrane proteins (e.g., recombinant soluble vascular cell adhesion molecule-1,
      rs VCAM-1) were tested for cell binding by the new cell-blotting technique using
      human lymphoid progenitor (NALM-6) and myeloid progenitor (KG1a) cell lines. Cell
      adhesion proteins retained their adhesion function in all cases tested.
      Specificity of cell binding on PVDF blot was demonstrated by inhibition of cell
      adhesion to WGA protein bands using an appropriate sugar, i.e., N-acetyl D
      glucosamine. The cell blotting assay was comparable in sensitivity to Coomassie
      blue staining of protein bands. The ability to conduct protein extraction,
      separation and blotting at low temperature avoids thermal denaturation, thereby
      preserving the adhesion properties of the proteins. The electrophoretic/blotting
      system has unique detergent removal/protein renaturation properties and the
      ability to preserve functionally active adhesion protein complexes. The cell
      blotting technique described is sufficiently robust for routine application in
      the investigation of novel cell adhesion proteins.

PMID- 7527068
TI  - Chamber for testing metered-dose propellant-driven aerosols of immunologically
      relevant proteins.
AB  - A small aerosol chamber was developed for testing and delivery of aerosols of
      immunologically important proteins to the respiratory tracts of rodents. The
      chamber was designed to accommodate the small aerosol volumes produced by metered
      dose propellant-driven aerosol canisters. Metered bursts of protein aerosols
      released into the chamber could be sampled for their particle sizes or used to
      expose the noses of up to six mice to the aerosols. The chamber consisted of a
      polyethylene tank with two removable plexiglass end plates. One end plate
      accommodated the propellant-driven, metered-dose, aerosol vial. The other end of
      the tank was fitted with a plate accepting aerosol sampling devices or a plate
      containing mouse restrainers. Uniform concentrations of aerosolized proteins were
      obtained at different positions in the chamber when sampled for particles of
      respirable size. Respirable-sized protein particles produced by propellant-driven
      aerosols ranged from 5 to 50% of total aerosolized protein. Propellant-driven
      aerosols of proteins released in the chamber produced aerosol particles
      equivalent to 15-26 micrograms of total protein exposure to the respiratory tract
      of each mouse. The chamber permitted aerosol releases without risk of operator
      exposure. This aerosol chamber will permit the testing of protein aerosols for
      their immunologic consequences to the respiratory tract. Potential proteins for
      testing in this device include immunizing vaccine antigens, immunomodulating
      cytokine proteins, and passive antibody aerosol therapies against respiratory
      infections.

PMID- 7527069
TI  - The generation of monoclonal antibodies recognising novel epitopes by
      immunisation with solid matrix antigen-antibody complexes reveals a polymorphic
      determinant on feline CD4.
AB  - Monoclonal antibodies were generated against the feline homologue of CD4 (fCD4)
      by immunisation of mice with solid matrix antigen-antibody complexes of
      monoclonal antibody Fel7 (anti-fCD4) and formalin-fixed Staphylococcus A (SMAA
      fCD4). The resulting fusion produced nine monoclonal antibodies each of which
      recognised a major population of feline lymphocytes and which immunoprecipitated
      a 55 kDa ligand from the feline T lymphosarcoma cell line 3201. Epitope mapping
      of the antibodies against soluble fCD4 by surface plasmon resonance indicated
      that the antibodies recognised five separate epitopes distinct from that defined
      by the Fel7 antibody used to prepare the SMAA-fCD4. These data demonstrate that
      SMAA complexes are an efficient means of generating monoclonal antibodies
      recognising novel epitopes on an antigen. One monoclonal antibody (vpg39)
      recognised an epitope that was expressed variably between cats, being either
      present or completely absent. Analysis of peripheral blood lymphocytes from
      specific pathogen free cats suggested that failure to react with the vpg39
      antibody was an inherited trait.

PMID- 7527070
TI  - Topics in free radical-mediated DNA damage: purines and damage amplification
      superoxic reactions-bleomycin, the incomplete radiomimetic.
AB  - Only a small percentage of the DNA damage set by ionizing radiation in the living
      cell manifests itself as lethal. It is now increasingly accepted that clustered
      lesions may constitute the kind of damage that the repair enzymes cannot
      adequately deal with. The question is raised as to whether damage amplification
      reactions (radical transfer reactions) may contribute to these clustered lesions,
      and examples of such damage amplification reactions are given. In one example a
      purine is involved. With 2'-deoxy adenosine and 2'-deoxy guanosine it is shown
      that these purine nucleosides undergo unexpected radical reactions. Evidence for
      the radical transfer from the purine to the sugar moiety is provided by the
      formation of the 5'-aldehydes. These products have been assayed with 2
      thiobarbituric acid (TBA), a reagent commonly applied to the detection of
      malonaldehyde. TBA-reactive material has also been assayed in gamma-irradiated
      and bleomycin-treated DNA. In gamma-irradiated DNA, about one-third of this is
      free malonaldehyde, while the major part of the TBA-reactive material remains
      bound to the DNA. In contrast, bleomycin-treated DNA yields practically no free
      malonaldehyde, and the major TBA-reactive products are identified as the thymine
      and adenine base propenals. There is also further unidentified low-molecular
      weight, TBA-reactive material. It is concluded that the drug must be involved not
      only in the first step (H-abstraction from the sugar moiety), but also in the
      subsequent free-radical reactions on the way to the base propenals.

PMID- 7527071
TI  - Comparative studies of UV-induced DNA cleavage by analogues of iodoHoechst 33258.
AB  - Following the earlier demonstration that iodo-Hoechst 33258 sensitizes DNA and
      cells to UVA, presumably mediated by formation of a carbon-centred radical on the
      ligand upon dehalogenation, three isomeric analogues of iodo-Hoechst 33258 have
      now been studied. The isomers differ in the location of the iodine atom in the
      phenyl ring of the ligand, relative to the site of attachment of the
      bibenzimidazole moiety, and are accordingly denoted ortho-, meta- and para
      iodoHoechst. Comparison of the ligands with respect to induction of DNA ssb in
      pBR322 DNA revealed a wide range of activity; (D37's vary by a factor of 37),
      decreasing in the order: ortho- > meta- and para- > iodoHoechst 33258.
      Preliminary dehalogenation studies suggest that the higher activity of the ortho
      isomer results more from increased cross-section for dehalogenation than from
      increased efficiency of strand breakage per dehalogenation event. However, the
      chemistry of strand breakage by the ortho-isomer is distinctive, and tentatively
      assigned to initial attack at the 1'-deoxyribosyl carbon; the other two isomers,
      like iodo-Hoechst 33258, attack the 5'-carbon. The results are discussed in terms
      of the spectrum of DNA strand breakage chemistry associated with ionizing
      radiation, and the potential of DNA strand breaking agents such as the
      iodoHoechst compounds to study the chemical and biological consequences of the
      different subclasses of initial DNA damage.

PMID- 7527072
TI  - Co-induction of neuronal interferon-gamma and nitric oxide synthase in rat motor
      neurons after axotomy: a role in nerve repair or death?
AB  - Induction of an interferon-gamma-like molecule, previously isolated from neurons
      (N-IFN-gamma), and of the neuronal isoform I of the synthetic enzyme of the free
      radical nitric oxide, nitric oxide synthase I, as well as of NADPH-diaphorase,
      were examined in axotomized dorsal motor vagal and hypoglossal neurons.
      Unilateral transection of the vagal and hypoglossal nerves was performed in the
      same rat and an induction of N-IFN-gamma and nitric oxide synthase I
      immunostaining as well as NADPH-diaphorase histochemical positivity was observed
      in the ipsilateral motoneurons after 2-4 days. The immuno- and enzyme
      histochemical positivities were much stronger in the dorsal motor vagal neurons
      than in hypoglossal neurons. Two and 4 weeks after axotomy N-IFN-gamma
      immunoreactivity and NADPH-diaphorase positivity persisted in the former, but
      started to decrease in the latter neurons. Previous data have shown that 23 weeks
      after nerve transection the majority of the dorsal motor vagal neurons are lost,
      while the majority of the hypoglossal neurons survive. The high and persistent
      expression of N-IFN-gamma and nitric oxide synthase I after axotomy in the dorsal
      motor vagal neurons, that are largely destined to die, indicates that the co
      induction of these two molecules may be implicated in the pathogenesis of
      neuronal degeneration.

PMID- 7527073
TI  - Immunoelectron microscopic localization of E-cadherin in dorsal root ganglia,
      dorsal root and dorsal horn of postnatal mice.
AB  - Sensory neurons and associated glial cells are known to express the cell-cell
      adhesion molecule E-cadherin. The cellular and subcellular localization of this
      molecule in the dorsal root ganglion, dorsal root, and spinal cord of postnatal
      mice was studied by the pre-embedding immunoelectron microscopic labelling
      technique. In the dorsal root and the superficial layer of the dorsal horn, a
      subset of fasciculating unmyelinated axons expressed E-cadherin at their axon
      axon contacts at all ages studied, and these axons were clustered together and
      segregated from E-cadherin-negative axons. In contrast, pre-myelinating large
      diameter axons in P2 mice as well as myelinated axons in mice from P14 to
      adulthood were E-cadherin-negative. Glial cells also expressed E-cadherin: In the
      dorsal root ganglia, all of the satellite cells expressed E-cadherin at contact
      sites with neurons, other satellite cells, and basal lamina, at all ages studied.
      In dorsal roots from P14 to adulthood, myelin-forming Schwann cells expressed E
      cadherin at the outer mesaxons and the contact sites with basal lamina. Non
      myelin-forming Schwann cells occasionally stained for this molecule at contact
      sites with the plasma membrane of E-cadherin-positive axons and at other sites.
      These results strongly suggest that E-cadherin plays an important role in the
      selective fasciculation of a particular subset of unmyelinated sensory fibres,
      and also in glial cell contacts.

PMID- 7527074
TI  - Three-dimensional morphology of astrocytes and oligodendrocytes in the intact
      mouse optic nerve.
AB  - The three-dimensional morphology of astrocytes and oligodendrocytes was analysed
      in the isolated intact mature mouse optic nerve, by correlating laser scanning
      confocal microscopy and camera lucida drawings of single cells, dye-filled with
      lysinated rhodamine dextran or horseradish peroxidase, respectively. These
      techniques enabled the entire process field of single dye-filled cells to be
      visualized in all planes and resolved the fine details of glial morphology.
      Morphometric analysis showed that the processes of all astrocytes had branches
      ending at the pial surface, on blood vessels, and freely in the nerve; branches
      ending in the nerve were described to end at nodes of Ranvier in the accompanying
      paper. Astrocytes were classified into a single morphological population in which
      each cell subserved multiple functions. The results of this study do not support
      the contention that astrocytes can be subdivided into two morphological and
      functional subtypes, namely type-1 and type-2, which have process ending either
      at the glia limitans or at nodes, respectively. Three-dimensional analysis of
      oligodendrocyte units, defined as the oligodendrocyte, its processes and the
      axons it ensheaths, showed the provision of single myelin segments for an average
      of 19 nearby axons (range 12-35) with a mean internodal length of 138 microns
      (range 50-350 microns). Mouse optic nerve oligodendrocytes were a homogeneous
      population and were markedly similar to those in the rat optic nerve. The results
      of our analysis of oligodendrocyte morphology are consistent with the view that
      the number and internodal length of myelin sheaths supported by a single
      oligodendrocyte are related to the diameter of the ensheathed axons.

PMID- 7527075
TI  - Modulation of associative memory function in a biophysical simulation of rat
      piriform cortex.
AB  - 1. Associative memory function was analyzed in a realistic biophysical simulation
      of rat piriform (olfactory) cortex containing 240 pyramidal cells and 58 each of
      two types of inhibitory interneurons. Pyramidal cell simulations incorporated six
      different intrinsic currents and three different synaptic currents. We
      investigated the hypothesis that acetylcholine sets the appropriate dynamics for
      learning within the network, whereas removal of cholinergic modulation sets the
      appropriate dynamics for recall. The associative memory function of the network
      was tested during recall after simulation of the cholinergic suppression of
      intrinsic fiber synaptic transmission and the cholinergic suppression of neuronal
      adaptation during learning. 2. Hebbian modification of excitatory synaptic
      connections between pyramidal cells during learning of patterns of afferent
      activity allowed the model to show the basic associative memory property of
      completion during recall in response to degraded versions of those patterns, as
      evaluated by a performance measure based on normalized dot products. 3. During
      learning of multiple overlapping patterns of afferent activity, recall of
      previously learned patterns interfered with the learning of new patterns. As more
      patterns were stored this interference could lead to the exponential growth of a
      large number of excitatory synaptic connections within the network. This runaway
      synaptic modification during learning led to excessive excitatory activity during
      recall, preventing the accurate recall of individual patterns. 4. Runaway
      synaptic modification of excitatory intrinsic connections could be prevented by
      selective suppression of synaptic transmission at these synapses during learning.
      This allowed effective recall of single learned afferent patterns in response to
      degraded versions of those patterns, without interference from other learned
      patterns. 5. During learning, cholinergic suppression of neuronal adaptation
      enhanced the activity of cortical pyramidal cells in response to afferent input,
      compensating for decreased activity due to suppression of intrinsic fiber
      synaptic transmission. This modulation of adaptation led to more rapid learning
      of afferent input patterns, as demonstrated by higher values of the performance
      measure. 6. During recall, when suppression of excitatory intrinsic synaptic
      transmission was removed, continued cholinergic suppression of neuronal
      adaptation led to the spread of excessive activity. More stable activity patterns
      during recall could be obtained when the cholinergic suppression of neuronal
      adaptation was removed at the same time as the cholinergic suppression of
      synaptic transmission. 7. A realistic biophysical simulation of the effects of
      acetylcholine on synaptic transmission and neuronal adaptation in the piriform
      cortex shows that these effects act together to set the appropriate dynamics for
      learning, whereas removal of both effects sets the appropriate dynamics for
      recall.

PMID- 7527076
TI  - Properties and ionic mechanisms of a metabotropic glutamate receptor-mediated
      slow afterdepolarization in neocortical neurons.
AB  - 1. Pyramidal neurons from layer V of rat neocortex were recorded intracellularly
      in a brain slice preparation to study their response to stimulation of
      metabotropic glutamate receptors (mGluRs) by bath application of the selective
      mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and
      by the nonselective agonists glutamate and quisqualate. 2. The principal
      postsynaptic effect of mGluR stimulation in the presence of ionotropic
      glutaminergic and muscarinic cholinergic antagonists was the appearance of a slow
      afterdepolarization (ADP) after evoked spikes. Only an afterhyperpolarization
      (AHP) was present in control perfusate. After 20 spikes evoked individually at
      100 Hz the ADP peaked at 317 +/- 117 (SD) ms after the spike train, ranged from 1
      to 12 mV in peak amplitude, and decayed over 7.4 +/- 4.7 s. This effect was not
      blocked by L-2-amino-3-phosphono-propionic acid (1 mM). Spikes evoked in the
      presence of the ionotropic glutamate receptor agonist R,S-alpha-amino-3-hydroxy-5
      methylisoxazole-4-proprionic acid (AMPA) did not have an ADP. 3. A detectable ADP
      appeared at concentrations of 0.1 microM quisqualate or 0.5 microM 1S,3R-ACPD.
      Maximum ADP amplitude was obtained with 5 microM quisqualate or 100 microM 1S,3R
      ACPD. The ADP appeared after a single evoked spike in most cells tested and ADP
      amplitude increased to a maximum as the number of spikes evoked at 100 Hz was
      increased to between 5 and 20. 4. The ionic mechanisms underlying the ADP were
      examined by ion substitution and the application of channel-blocking agents. No
      difference in ADP amplitude was observed when the recording electrode contained
      CH3SO4. instead of Cl.. The ADP was present after 3 mM extracellular Cs+ were
      added to block the hyperpolarization-activated cation current or when 100 microM
      Ba2+ were included to block voltage-gated K+ currents. The ADP was abolished when
      Mn2+ was substituted for Ca2+ in the perfusate or when the Ca2+ chelator 5,5'
      dimethyl-bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid was included in the
      recording electrode. A large ADP followed Ca2+ spikes evoked in the presence of 1
      microM tetrodotoxin with 20 mM tetraethylammonium in the perfusate or with Cs+
      substituted for K+ in the recording electrode. The amplitude of the ADP after the
      Ca2+ spikes was reduced by 49% when extracellular Na+ concentration was reduced
      from 136 to 26 mM. 5. The voltage dependence of the ADP was examined in relation
      to K+ equilibrium potential (EK).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7527077
TI  - A model of spindle rhythmicity in the isolated thalamic reticular nucleus.
AB  - 1. The oscillatory properties of the isolated reticular (RE) thalamus were
      modeled with the use of compartmental models of RE cells. Hodgkin-Huxley type
      kinetic models of ionic channels were derived from voltage- and current-clamp
      data from RE cells. Interactions between interconnected RE cells were simulated
      with the use of a kinetic model of gamma-aminobutyric acid (GABA) inhibitory
      synapses. 2. The intrinsic bursting properties of RE cells in the model were due
      to the presence of a low-threshold Ca2+ current and two Ca(2+)-activated
      currents. The properties of these model RE cells were compared with RE neurons
      recorded intracellularly in vivo in cats. 3. Model RE cells densely
      interconnected with GABAA synapses produced synchronous oscillations at a
      frequency close to that of spindles (7-14 Hz). Networks of RE neurons organized
      in a two-dimensional array with only proximal connectivity also exhibited
      synchronized oscillations in the spindle range. In addition, the proximally
      connected network showed periods of high and low synchronicity, giving rise to
      waxing and waning oscillations in the population of RE cells. 4. The
      spatiotemporal behavior of the network was investigated during waxing and waning
      oscillations. The waxing and waning emerged as an alternation between periods of
      desynchronized and synchronized activity, corresponding to periods of irregular
      and coherent spatial activity. During synchronized periods, the network displayed
      propagating coherent waves of synchronous activity that had a tendency to form
      spirals. 5. Networks of model RE neurons fully connected through GABAB synapses
      exhibited perfectly synchronous oscillations at lower frequencies (0.5-1 Hz), but
      two-dimensional networks with proximal GABAB connectivity failed to synchronize.
      6. These simulations demonstrate that networks of model neurons that include the
      main intrinsic currents found in RE cells can generate waxing and waning
      oscillatory activity similar to the spindle rhythmicity observed in the isolated
      RE nucleus in vivo. The model reveals the interplay between the intrinsic
      rhythmic properties of RE cells and the fast synaptic interactions in organizing
      synchronized rhythmicity.

PMID- 7527078
TI  - Synaptic integration in a model of cerebellar granule cells.
AB  - 1. We have developed a compartmental model of a turtle cerebellar granule cell
      consisting of 13 compartments that represent the soma and 4 dendrites. We used
      this model to investigate the synaptic integration of mossy fiber inputs in
      granule cells. 2. The somatic compartment contained six active ionic
      conductances: a sodium conductance with fast activation and inactivation
      kinetics, gNa; a high-voltage-activated calcium conductance, gCa(HVA); a delayed
      potassium conductance, gK(DR); a transient potassium conductance, gK(A); a slowly
      relaxing mixed Na+/K+ conductance activating at hyperpolarized membrane
      potentials, gH, and a calcium- and voltage-dependent potassium conductance,
      gK(Ca). The kinetics of these conductances was derived from electrophysiological
      studies in a variety of preparations, including turtle and rat granule cells. 3.
      In the soma, dynamics of intracellular free Ca2+ was modeled by incorporation of
      a Na+/Ca2+ exchanger, radial diffusion, and binding sites for Ca2+. 4. The model
      of the turtle granule cell exhibited depolarization-induced action potential
      firing with properties closely resembling those seen with intracellular
      recordings in turtle granule cells in vitro. 5. In the most distal compartments
      of the dendrites, mossy fiber activity induced synaptic currents mediated by
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D
      aspartate (NMDA)-type of glutamate receptors. The strength of synaptic inputs
      chosen was such that the synaptic potential induced by synchronous activation of
      two mossy fiber synapses reached threshold for induction of a single action
      potential. 6. The slow time course of the NMDA synaptic current together with the
      slow relaxation kinetics of gH significantly affected the temporal summation of
      excitatory synaptic potentials. A priming action potential evoked by mossy fiber
      stimulation increased the maximal time interval between two synaptic potentials
      capable to reach again threshold for a subsequent action potential. This time
      interval then decreased in parallel with the decay of the NMDA synaptic current,
      reached a minimum after 200 ms, and slowly recovered with reactivation of gH. 7.
      Repetitive, steady activation of synaptic conductances by a single mossy fiber at
      different frequencies induced action potential firing with a sharp threshold at
      12 Hz. Activity of a single or of several mossy fibers induced firing of the
      granule cell at a frequency close to that induced when the average synaptic
      current was directly injected into the cell. The mossy fiber activity-granule
      cell firing frequency curve was close to linear with a slope of about one-half
      for input frequencies < or = 400 Hz.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7527080
TI  - Dermatomyositis following infection with hepatitis C virus.

PMID- 7527079
TI  - Substance P-immunoreactive and protein gene product 9.5-immunoreactive nerve
      fibres in bone marrow of rat coccygeal vertebrae.
AB  - Previous investigations have focused mainly on the nerve terminals in soft
      tissues surrounding the vertebrae to determine the source of spinal pain. Our
      study on rat coccygeal vertebrae compared intramedullary immunostaining for
      substance P with that of a more generally distributed neural marker, protein gene
      product 9.5, to suggest another source of spinal pain. Free intramedullary fibres
      staining for protein gene product 9.5 were rare compared with the abundant
      staining associated with intramedullary vessels. Shortly after entering the
      marrow with the nutrient vessels, substance P-immunoreactive fibres parted from
      the vessels and then proceeded longitudinally and terminated on the end-plates.
      Other (although fewer) substance P-immunoreactive fibres entered the marrow at
      enthetic aspects of the vertebrae. The presence of free substance P
      immunoreactive fibres innervating endplates and penetrating entheses suggests
      that they may represent a novel source of spinal pain.

PMID- 7527081
TI  - Primary isolates of human immunodeficiency virus type 1 are relatively resistant
      to neutralization by monoclonal antibodies to gp120, and their neutralization is
      not predicted by studies with monomeric gp120.
AB  - A panel of anti-gp120 human monoclonal antibodies (HuMAbs), CD4-IgG, and sera
      from people infected with human immunodeficiency virus type 1 (HIV-1) was tested
      for neutralization of nine primary HIV-1 isolates, one molecularly cloned primary
      strain (JR-CSF), and two strains (IIIB and MN) adapted for growth in transformed
      T-cell lines. All the viruses were grown in mitogen-stimulated peripheral blood
      mononuclear cells and were tested for their ability to infect these cells in the
      presence and absence of the reagents mentioned above. In general, the primary
      isolates were relatively resistant to neutralization by the MAbs tested, compared
      with the T-cell line-adapted strains. However, one HuMAb, IgG1b12, was able to
      neutralize most of the primary isolates at concentrations of < or = 1
      microgram/ml. Usually, the inability of a HuMAb to neutralize a primary isolate
      was not due merely to the absence of the antibody epitope from the virus; the
      majority of the HuMAbs bound with high affinity to monomeric gp120 molecules
      derived from various strains but neutralized the viruses inefficiently. We infer
      therefore that the mechanism of resistance of primary isolates to most
      neutralizing antibodies is complex, and we suggest that it involves an
      inaccessibility of antibody binding sites in the context of the native
      glycoprotein complex on the virion. Such a mechanism would parallel that which
      was previously postulated for soluble CD4 resistance. We conclude that studies of
      HIV-1 neutralization that rely on strains adapted to growth in transformed T-cell
      lines yield the misleading impression that HIV-1 is readily neutralized. The more
      relevant primary HIV-1 isolates are relatively resistant to neutralization,
      although these isolates can be potently neutralized by a subset of human
      polyclonal or monoclonal antibodies.

PMID- 7527083
TI  - Construction and properties of pseudorabies virus recombinants with altered
      control of immediate-early gene expression.
AB  - To investigate how altered control of expression of the essential immediate-early
      (IE) gene of pseudorabies virus influences virus replication and virulence, we
      replaced the IE promoter with the tissue-specific promoters of the bovine
      cytokeratin IV gene (CKIV), the bovine cytokeratin VIb gene (CKVIb), or the
      inducible promoter of Drosophila heat shock gene HSP70. We compared expression of
      the IE gene of the wild-type virus and recombinant viruses in different cell
      types and at different temperatures and found that IE expression had become cell
      type or temperature dependent. When a recombinant virus was titrated on
      nonpermissive cells or was titrated at nonpermissive temperatures in vitro, the
      plating efficiency was reduced by more than 99%. Mice were inoculated
      subcutaneously (s.c.), intraperitoneally (i.p.), or intranasally (i.n.) with a
      dose equal to 100 times the 50% lethal dose of the wild-type virus. After
      inoculation with temperature-sensitive recombinant N-HSP, two (s.c.), two (i.p.),
      and four (i.n.) of five mice died. However, at this dose, recombinant N-CKIV,
      which contains a promoter specific for stratified epithelial tissue of the tongue
      mucosa, was not lethal when inoculated s.c. or i.p. but killed four mice when
      inoculated i.n. Recombinant N-CKVIb, which contains a promoter specific for the
      suprabasal layers of the epidermis, was not lethal after inoculation by any of
      the three routes. In explant cultures of nasal mucosa of pigs, replication of N
      CKIV and N-CKVIb was not markedly reduced in the epithelium. However, in contrast
      to results obtained with wild-type virus, infection of the stroma was not
      observed. We conclude that the replicative ability and virulence of pseudorabies
      virus can be influenced by altering control of expression of the IE gene.

PMID- 7527082
TI  - A human monoclonal antibody to a complex epitope in the V3 region of gp120 of
      human immunodeficiency virus type 1 has broad reactivity within and outside clade
      B.
AB  - We have used virus neutralization and antibody-binding techniques to define the
      epitope for a human monoclonal antibody, designated 19b, within the V3 region of
      the gp120 surface glycoprotein of human immunodeficiency virus type 1. Unusually,
      the 19b epitope encompasses residues on both flanks of the V3 loop. However, 19b
      binding to gp120 is independent of sequences at the crown of the V3 loop,
      provided that they are compatible with the formation of a type II beta turn that
      is presumably necessary to juxtapose the antigenic residues on the V3 flanks. By
      comparing the V3 sequences of virus gp120s able and unable to bind 19b, we were
      able to define the canonical 19b epitope as -I----G--FY-T, where residues at the
      positions indicated by the gaps do not contribute directly to the 19b-binding
      site. A few conservative substitutions at the more critical residues are also
      compatible with 19b binding. Inspection of V3 sequences in the human
      immunodeficiency virus database indicated that the canonical 19b epitope is well
      conserved among isolates from the North American-European clade B and also among
      clade E isolates from Thailand and clade F isolates from Brazil. A minority of
      gp120s from clades A and C also possess the 19b epitope. Consistent with the
      theoretical predictions of its cross-clade reactivity, 19b was found to bind to
      gp120s from clades A, B, C, E, and F in immunoassays. However, 19b was not able
      to reduce the infectivity of primary viruses from clades A, E, and F that were
      predicted to possess the 19b epitope and only modestly reduced the infectivity of
      a clade C virus at low input virus concentrations. Cross-clade neutralization via
      V3-directed antibodies may, therefore, be difficult, even if the antibodies show
      broad reactivities in binding assays and the viruses theoretically possess the
      relevant binding site.

PMID- 7527084
TI  - Identification and characterization of monoclonal antibodies specific for
      polymorphic antigenic determinants within the V2 region of the human
      immunodeficiency virus type 1 envelope glycoprotein.
AB  - We have identified six monoclonal antibodies (MAbs) mapping to both linear and
      conformation-dependent epitopes within the V2 region of the human
      immunodeficiency virus type 1 clone HXB10. Three of the MAbs (12b, 66c, and 66a)
      were able to neutralize the molecular clones HXB10 and HXB2, with titers in the
      range of 9.5 to 20.0 micrograms/ml. MAbs mapping to the crown of the V2 loop
      (12b, 60b, and 74) bound poorly to cell surface-expressed oligomeric gp120,
      suggesting an explanation for the poor or negligible neutralizing activity of
      MAbs to this region. In contrast, MAbs 12b and 60b demonstrated good reactivity
      with recombinant gp120 in an enzyme-linked immunosorbent assay format, suggesting
      differential epitope exposure between the recombinant and native forms of gp120.
      Cross-competition analysis of these MAbs and additional V1V2 MAbs for gp120
      binding enabled us to assign the MAbs to six groups (A to F). Selection of
      neutralization escape mutants with MAbs 10/76b and 11/68b, belonging to
      nonoverlapping competition groups, identified amino acid changes at residues 165
      (I to T) and 185 (D to N), respectively. Interestingly, these escape variants
      remained sensitive to neutralization by the nonselecting V2 MAbs. All MAbs
      demonstrated good recognition of IIIB viral gp120 yet failed to neutralize
      nonclonal stocks of IIIB. In addition, MAbs 12b and 62c bound MN and RF viral
      gp120, respectively, yet failed to neutralize the respective isolates. Cloning
      and expression of a library of gp120 and V1V2 fragments from IIIB-, MN-, and RF
      infected H9 cultures identified a number of polymorphic sites, resulting in
      antigenic variation and subsequent loss of V2 MAb recognition. In contrast, the
      V3 region from the clones of the same isolates showed no amino acid changes,
      suggesting that the V2 region is polymorphic in long-term-passaged laboratory
      isolates and may account for the reduced antibody recognition observed.

PMID- 7527086
TI  - Resistance to nucleoside analogs of selective mutants of human immunodeficiency
      virus type 2 reverse transcriptase.
AB  - We have studied selected mutants of human immunodeficiency virus type 2 (HIV-2)
      reverse transcriptase (RT) in a cell-free system in order to assess whether the
      mutant proteins exhibit a reduction in the sensitivity to nucleoside analog
      inhibitors similar to that of HIV-1 RT. We have modified, by site-directed
      mutagenesis, several of those amino acid residues so that their equivalent
      substitutions in HIV-1 RT have led to the formation of HIV-1 RT variants with the
      highest degree of resistance to dideoxynucleoside triphosphates (i.e., Glu-89-
      >Gly, Leu-74-->Val, and Ser-215-->Tyr [which is comparable to the Thr-215-->Tyr
      mutation of HIV-1 RT] and the double mutations Glu-89-->Gly/Ser-215-->Tyr and and
      Leu-74-->Val/Ser-215-->Tyr). The similarity found between resistance of the newly
      generated HIV-2 RT mutants to nucleoside analogs and that of the comparable
      mutants of HIV-1 RT can support the notion that the overall protein folding
      around the DNA polymerase active site in HIV-2 RT is quite similar to that of HIV
      1 RT.

PMID- 7527085
TI  - Reversal of the interferon-sensitive phenotype of a vaccinia virus lacking E3L by
      expression of the reovirus S4 gene.
AB  - The vaccinia virus (VV) E3L gene, which encodes a potent inhibitor of the
      interferon (IFN)-induced, double-stranded RNA (dsRNA)-dependent protein kinase,
      PKR, is thought to be involved in the IFN-resistant phenotype of VV. The E3L gene
      products, p25 and p20, act as inhibitors of PKR, presumably by binding and
      sequestering activator dsRNA from the kinase. In this study we demonstrate that
      VV with the E3L gene specifically deleted (vP1080) was sensitive to the antiviral
      effects of IFN and debilitated in its ability to rescue vesicular stomatitis
      virus from the antiviral effects of IFN. Infection of L929 cells with E3L-minus
      virus led to rRNA degradation typical of activation of the 2'-5'-oligoadenylate
      synthetase/RNase L system, and extracts of infected cells lacked the PKR
      inhibitory activity characteristic of wild-type VV. The reovirus S4 gene, which
      encodes a dsRNA-binding protein (sigma 3) that can also inhibit PKR activation by
      binding and sequestering activator dsRNA, was inserted into vP1080. The resultant
      virus (vP1112) was partially resistant to the antiviral effects of IFN in
      comparison with vP1080. Further studies demonstrated that transient expression of
      the reovirus sigma 3 protein rescued E3L-minus VV replication in HeLa cells. In
      these studies, rescue by sigma 3 mutants correlated with their ability to bind
      dsRNA. Finally, vP112 was also able to rescue the replication of the IFN
      sensitive virus vesicular stomatitis virus in a manner similar to that of wild
      type VV. Together, these results suggest that the reovirus S4 gene can replace
      the VV E3L gene with respect to interference with the IFN-induced antiviral
      activity.

PMID- 7527087
TI  - Isolation of a monoclonal antibody which blocks vaccinia virus infection.
AB  - We have isolated a monoclonal antibody, B2, that neutralizes vaccinia virus
      infection. B2 reacts with a trypsin-sensitive cell surface epitope. B2 does not
      neutralize infection of herpes simplex virus, suggesting that the B2-reactive
      epitope is specifically involved in vaccinia virus entry. A survey of 12
      different cell lines reveals a correlation between B2 reactivity and
      susceptibility to vaccinia virus infection. In addition, B2 interferes with
      vaccinia virus adsorption to target cells. Taken together, the B2-reactive
      epitope is part of a receptor that appears important for vaccinia virus entry.

PMID- 7527088
TI  - Comparative sequence analysis of the reovirus S4 genes from 13 serotype 1 and
      serotype 3 field isolates.
AB  - The reovirus sigma 3 protein is a major outer capsid protein that may function to
      regulate translation within infected cells. To facilitate the understanding of
      sigma 3 structure and functions and the evolution of mammalian reoviruses, we
      sequenced cDNA copies of the S4 genes from 10 serotype 3 and 3 serotype 1
      reovirus field isolates and compared these sequences with sequences of prototypic
      strains of the three reovirus serotypes. We found that the sigma 3 proteins are
      highly conserved: the two longest conserved regions contain motifs proposed to
      function in binding zinc and double-stranded RNA. We used the 16 viral isolates
      to investigate the hypothesis that structural interactions between sigma 3 and
      the cell attachment protein, sigma 1, constrain their evolution and to identify a
      determinant within sigma 3 that is in close proximity to the sigma 1
      hemagglutination site.

PMID- 7527090
TI  - [Clinical characterization of diabetes mellitus in the families with
      mitochondrial encephalomyopathies].
AB  - We clinically characterized 18 diabetic patients in 7 families with mitochondrial
      encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) and
      mitochondrial DNA mutations of tRNALEU(UUR) (3243), 5 diabetics in a family with
      myoclonic epilepsy and ragged red fiber (MERRF) and tRNALYS (8344) mutation and
      11 diabetics in a family with chronic external ophthalmoplegia (CPEO) and
      multiple deletions. Insulin secretory capacities were significantly reduced in
      the mutant relatives, as compared with the non-mutant members. It is speculated
      that the mutation-induced OPHOS defects in the pancreatic beta- cells might
      result in insulin secretory defects.

PMID- 7527091
TI  - [The indications for the surgical treatment of prostatic adenoma].
AB  - Proceeding from a comprehensive literature survey, an attempt is made to
      substantiate the single indications for operative treatment of prostate
      hypertrophy cases. Special attention is focused on the quantity of residual
      urine, clinical relevance of the uroflowmetric study, and individual assessment
      of the urologist, depending on his surgical experience. Last but not least
      important is grouping of the individual symptoms of prostate hypertrophy under
      the heading "prostatism" syndrome, since they serve not merely for preoperative
      evaluation, but also as an assessment criterion of the postoperative condition.

PMID- 7527092
TI  - [The conservative treatment of early-stage benign prostatic hypertrophy].
AB  - After outlining the methods currently used in benign prostate hyperplasia (BPH)
      treatment, data defining some etiological aspects of the disease are briefly
      analyzed. Initial experience had with the treatment of early stage BPH using
      Permixon--a drug exerting effect on alpha-2 reductase--is described. The results
      in a series of twenty-seven patients presenting BPH are encouraging.

PMID- 7527089
TI  - Relationship between the V3 loop and the phenotypes of human immunodeficiency
      virus type 1 (HIV-1) isolates from children perinatally infected with HIV-1.
AB  - The third variable region (V3) of the envelope protein of human immunodeficiency
      virus type 1 (HIV-1) contains group- and type-specific epitopes for neutralizing
      antibodies and contains determinants involved in viral tropism and syncytium
      inducing (SI) activity. We studied the in vivo relationship between V3 sequences
      and viral phenotypes in 24 perinatally HIV-1-infected children. To avoid in vitro
      selection of intrapatient minor variants, genetic studies were performed directly
      on uncultured peripheral blood mononuclear cells (PBMC), and the tropisms of HIV
      1 isolates were evaluated by culturing patients' PBMC directly with monocyte
      derived macrophages, lymphocytes, and MT-2 cells. According to their phenotypes,
      we could define five types of primary isolates: (i) non-syncytium-inducing (NSI)
      macrophagetropic, (ii) NSI macrophage-lymphotropic, (iii) NSI lymphotropic, (iv)
      SI lympho-T-cell line-tropic, and (v) SI pleiotropic. The SI viral phenotype was
      correlated with a more advanced status of disease. Genetic analysis of
      intrapatient molecular variants revealed that no relationship between the degree
      of intrapatient V3 variability and the pattern of viral tropism existed;
      moreover, within a single patient, the values for V3 variability between CD4+
      lymphocytes and CD14+ monocytes were similar, thus suggesting that in vivo
      variability of the monocytotropic variants is more extensive than previously
      appreciated. A comparison between the intrapatient major variants and the
      phenotype of primary isolates disclosed that a negatively charged amino acid at
      residue site 25 was associated with an NSI macrophage- and macrophage
      lymphotropic viral phenotype. Finally, by comparing the V3 sequences derived from
      our study population with those of several prototypes, we observed that the
      majority of isolates circulating in Italy are related to the North American
      subtype B macrophagetropic isolates.

PMID- 7527093
TI  - Spontaneous mesothelioma in a Syrian hamster.

PMID- 7527094
TI  - The endothelium and vascular effects of the ACE inhibitor trandolaprilat.
AB  - Experiments were designed to study the effects of trandolaprilat on endothelium
      dependent responses in isolated blood vessels. Rings of either femoral or left
      circumflex coronary arteries of the dog or thoracic aortas of normotensive rats
      were suspended in organ chambers for isometric tension recording. During
      contractions induced by prostaglandin F2 alpha, trandolaprilat did not cause
      direct endothelium-dependent or -independent relaxation. However, when given to
      preparations incubated with angiotensin I or bradykinin, the compound evoked
      significant endothelium-dependent relaxation. By contrast, trandolaprilat failed
      to cause any change in tension when given in the presence of acetylcholine (ACh).
      In rings of femoral arteries, trandolaprilat potentiated the endothelium
      dependent relaxation evoked by bradykinin and adenosine diphosphate; it did not
      modify the endothelium-dependent relaxations induced by ACh, substance P, or
      thrombin. In rings of femoral arteries without endothelium, trandolaprilat
      augmented relaxation induced by adenosine diphosphate (ADP) but not by adenosine.
      In perfused coronary arteries with but not those without endothelium,
      trandolaprilat caused relaxation in the absence of exogenous bradykinin (or ADP).
      These experiments suggest that trandolaprilat does not directly release
      endothelium-derived relaxing factor from the endothelial cells, does not
      interfere with the ability of the endothelium to release endothelium-derived
      relaxing factor, augments the endothelium-dependent responses to bradykinin
      (given exogenously or produced locally) and angiotensin I by direct interaction
      with converting enzyme, and potentiates the relaxation induced by ADP by
      augmenting its direct effect on vascular smooth muscle.

PMID- 7527095
TI  - Compared properties of trandolapril, enalapril, and their diacid metabolites.
AB  - The effects of 14-day trandolapril or enalapril treatment of spontaneously
      hypertensive rats (SHRs) were studied on blood pressure and angiotensin
      converting enzyme (ACE) activity measured ex vivo in various organs. Both ACE
      inhibitors caused dose-dependent decreases in blood pressure and ACE activity,
      trandolapril being 30- and 400- to 1,000-fold more active than enalapril on blood
      pressure and ACE activity, respectively. However, comparison of ACE inhibitory
      activities of the diacid forms of trandolapril and enalapril, i.e.,
      trandolaprilat and enalaprilat, measured in vitro on various tissues, showed that
      trandolaprilat was only three- to fivefold more active than enalaprilat. To
      understand the reasons for such discrepancies between ex vivo effects of ACE
      inhibitors and in vitro actions of their diacid metabolites, we measured the
      lipophilicities of the compounds and investigated the possibility that
      trandolapril could display an ACE inhibitory effect by itself. Trandolaprilat was
      found to be far more lipophilic than enalaprilat, as shown by reverse-phase high
      performance liquid chromatography studies performed at pH 7.4 (log kw7.4 = 1.487
      vs. 0.108). In addition, trandolapril was practically as active in vitro as its
      diacid metabolite (IC50 = 2.5 vs. 1.35 nM) in inhibiting ACE activity in the
      aorta, whereas enalapril was practically devoid of any effect (IC50 = 240 nM).
      Measurements of relative affinities of inhibitors or metabolites for purified
      human renal ACE showed that trandolapril displayed about 20% of the affinity of
      its diacid metabolite (IC50 = 15 vs. 3.2 nM); enalaprilat affinity (34 nM) was
      within the same range as those of trandolapril and trandolaprilat, whereas
      enalapril displayed a very low affinity for the purified enzyme (IC50 = 50
      microM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527096
TI  - Trandolapril dose-response in spontaneously hypertensive rats: effects on ACE
      activity, blood pressure, and cardiac hypertrophy.
AB  - The dose-related effects of trandolapril on serum angiotensin-converting enzyme
      (ACE) activity, blood pressure and cardiac hypertrophy were studied after 2-week
      oral treatment in adult spontaneously hypertensive rats. Trandolapril caused a
      dose-dependent decrease in mean blood pressure at doses of 0.03-3 mg/kg.
      Inhibition of serum ACE was demonstrated by even the lowest dose (-9% at 0.003
      mg/kg), was about 40% at 0.03 mg/kg, and rose to 84% at 3 mg/kg. Regression of
      cardiac hypertrophy (heart:body weight) was seen at doses of trandolapril as low
      as 0.03 mg/kg (-5.1%), which was also the minimal effective antihypertensive
      dose. Clear dose-response curves were observed for trandolapril from 0.03 mg/kg
      upwards with respect to hypotensive effect and regression of cardiac hypertrophy,
      which were not seen with enalapril. Enalapril had no significant effect on plasma
      ACE activity except at the highest dose (10 mg/kg), despite demonstrating
      hypotensive effects with smaller doses. These results indicate that trandolapril
      is a more potent (by a factor of about 30) inhibitor of ACE than enalapril (only
      34% inhibition at 10 mg/kg) and causes a greater degree of regression of cardiac
      hypertrophy.

PMID- 7527097
TI  - Effect of chronic converting-enzyme inhibition on kidney function of senescent
      hypertensive rats.
AB  - The age-related changes in the structure and the function of the kidney and the
      effect of chronic inhibition of angiotensin-converting enzyme (ACE) activity on
      these alterations were assessed in senescent, genetically hypertensive rats. Mean
      blood pressure was unchanged between 6 and 21 months, being 136 +/- 10 and 135 +/
      21 mm Hg, respectively. Hypertrophy of the glomeruli with a high incidence of
      glomerulosclerosis was reported in the 21-month-old animals. Renal blood flow,
      glomerular filtration rate, and filtration fraction were reduced between 6 and 21
      months, whereas albuminuria and cGMP excretion were markedly enhanced with aging.
      Chronic ACE inhibition by administration of 0.3 mg/kg/day trandolapril from 18-21
      months increased the life expectancy of the animals without affecting their mean
      blood pressure. The incidence of glomerular lesions and the excretion of enzymes
      that reflected the integrity of tubular and glomerular cells were not altered by
      ACE inhibition. On the other hand, the filtration fraction was restored in the 21
      month-old treated animals, and the age-related albuminuria and rise in cGMP
      excretion were prevented by ACE inhibition. These results indicated that ACE
      inhibitor administered at the end of the life of senescent hypertensive rats was
      able to prevent some of the age-related changes in kidney function when
      glomerulosclerosis was already present.

PMID- 7527098
TI  - Effects of 4 weeks of treatment with trandolapril on renal hypertension and
      cardiac and vascular hypertrophy in the rat.
AB  - The effects of the angiotensin-converting enzyme inhibitor trandolapril were
      studied using a Goldblatt (two-kidney, one-clip) rat model of renovascular
      hypertension after 4 weeks of oral treatment at 0.3 or 1 mg/kg/day. The effects
      of trandolapril on blood pressure and on cardiac and vascular hypertrophy were
      analyzed in comparison with the control group. Trandolapril produced a rapid,
      dose-dependent decrease in blood pressure, which plateaued after 2 weeks of
      treatment. Complete normalization of blood pressure was observed at a daily dose
      of 1 mg/kg. Dose-dependent inhibition of cardiac hypertrophy was also observed,
      heart:body weight ratio being decreased by 17 and 30% at 0.3 and 1 mg/kg,
      respectively, leading to a normalization of this parameter at the higher dose
      compared with normotensive controls. Similarly, trandolapril produced a marked
      decrease in vascular wall hypertrophy in both the mesenteric artery and the
      aorta. Indeed, complete normalization of media thickness was observed, compared
      with the normotensive control group, at 1 mg/kg of trandolapril. These results
      show that short-term treatment with trandolapril can induce complete regression
      of cardiac and vascular hypertrophy, which is associated with the development of
      renal hypertension.

PMID- 7527099
TI  - Effects of subchronic treatment with trandolapril and enalapril on cardiovascular
      morphologic alterations in the aged spontaneously hypertensive rat with heart
      failure.
AB  - The effects of a 3-month treatment period with the angiotensin-converting enzyme
      (ACE) inhibitors trandolapril (0.3 mg/kg/day, p.o.) and enalapril (10 mg/kg/day,
      p.o.) on hemodynamics, cardiac hypertrophy, and vascular structures were examined
      in old spontaneously hypertensive rats (SHRs) (24 months at the end of treatment)
      presenting with congestive heart failure. During the course of treatment, the
      mortality rate was lower in the two treated groups than in the control group. At
      the end of treatment, serum ACE activity was inhibited by 63 and 33% by
      trandolapril and enalapril, respectively, but the decrease in blood pressure they
      induced was not significant. The atrial natriuretic factor(ANF) plasma levels and
      cyclic GMP urine excretion were about 10-fold and 3-fold higher, respectively, in
      old SHRs than in old Wistar rats. These values were markedly decreased by both
      ACE inhibitors. The ventricular hypertrophy was greatly decreased by both
      compounds (-24% by trandolapril and -26% by enalapril). In the aorta, the media
      hypertrophy was significantly decreased and nuclear density increased to a
      similar extent by both ACE inhibitors. In the mesenteric artery, trandolapril
      treatment induced a complete regression of the media hypertrophy and a marked
      decrease in extracellular matrix surface. In addition, the collagen network
      appeared less dissociated in the treated animals. Similarly the nuclear density
      was increased and the surface of cell nuclei was decreased by trandolapril.
      Enalapril appeared much less potent on these parameters. These data demonstrate
      that treatment with trandolapril of aged SHRs presenting with heart failure
      results in an increase in survival of the animals and a marked regression of
      cardiac and vascular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527100
TI  - Trandolapril: pharmacokinetics of single oral doses in healthy male volunteers.
AB  - The pharmacokinetics and dose proportionality of trandolapril, a new angiotensin
      converting enzyme (ACE) inhibitor, were investigated in 12 healthy male
      volunteers in a four-way randomized crossover study over the therapeutic dose
      range, 0.5-4 mg. Trandolapril is rapidly absorbed, with a single elimination half
      life (t1/2) of 0.72 h, irrespective of dose. Peak plasma levels (Cmax) occurred
      at 0.5 h and were proportional to the dose, as was the area under the plasma
      concentration-time curve (AUC). Concentration of the active metabolite
      (trandolaprilat) increased with increasing doses but in a nonlinear fashion,
      probably owing to saturable plasma ACE binding. However, the Cmax and AUC values
      for trandolaprilat were directly proportional to the highest doses, 2 and 4 mg,
      suggesting linear kinetics for the trandolaprilat, which is not bound to ACE.
      Trandolapril showed linear kinetics but trandolaprilat showed some features of
      nonlinear kinetics, particularly at low doses.

PMID- 7527101
TI  - Pharmacokinetics and pharmacodynamics of trandolapril after repeated
      administration of 2 mg to young and elderly patients with mild-to-moderate
      hypertension.
AB  - The new angiotensin-converting enzyme (ACE) inhibitor trandolapril 2 mg was
      administered daily for 10 consecutive days to young (mean age +/- SEM 44.1 +/-
      2.3 years; n = 10) and elderly (mean age +/- SEM 69.3 +/- 0.9 years; n = 14)
      patients with mild-to-moderate hypertension. All groups had similar baseline
      blood pressures: mean 164/100 mm Hg. Maximal plasma ACE inhibition on day 10 and
      residual inhibition 24 h after the last dose was the same, irrespective of age:
      young, 85.2 and 57.4%; elderly 89.1 and 59.8%, respectively. There was no
      difference between the results on day 1 for the young and elderly groups. The
      absorption of trandolapril was rapid (< 1 h in all groups). The peak plasma
      concentration (Cmax) and the area under the plasma concentration-time curve (AUC)
      were slightly higher in the older group, but the elimination half-life (t1/2) was
      the same, with no accumulation after repeat dosing. A steady-state plasma
      concentration of the active metabolite of trandolapril, trandolaprilat, was
      reached after 4 days in the two groups, with similar accumulation ratios (young,
      1.48; elderly, 1.49). At steady state, the Cmax and AUC 0-24 h for trandolaprilat
      were similar in the two groups: young, 7.49 +/- 0.98 ng/ml and 82.27 +/- 6.95
      ng/ml/h; elderly, 8.35 +/- 0.67 ng/ml/h and 96.75 +/- 5.67 ng/ml/h. Maximal
      reductions in systolic/diastolic blood pressures (at 6 h postdose) were -14.1%/
      16.1% in young patients and -14.6%/-17.5% for the elderly. Significant blood
      pressure reduction persisted for 48 h after the last dose.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7527102
TI  - Pharmacokinetics and pharmacodynamics of trandolapril after repeated
      administration of 2 mg to patients with chronic renal failure and healthy control
      subjects.
AB  - A new, long-acting angiotensin-converting enzyme (ACE) inhibitor, trandolapril,
      was administered daily for 10 days to 13 patients with chronic renal failure
      [CRF; creatinine clearance (CLCR) 7-55 ml/min/1.73 m2) and 8 healthy volunteers
      (CLCR > 80 ml/min/1.73 m2)]. Plasma ACE inhibition parameters were the same,
      irrespective of the degree of renal insufficiency, although renal failure tended
      to prolong ACE inhibition. The pharmacokinetics of trandolapril were not affected
      by CRF; hence, no accumulation of trandolapril was detected. After single or
      repeated administration the active metabolite, trandolaprilat, showed an inverse
      correlation between maximal plasma concentrations (Cmax) and CLCR (r = -0.676 day
      1 and r = -0.864 day 10) and area under the concentration-time curve (AUC) and
      CLCR (r = -0.635 day 1 and r = -0.794 day 10). The renal clearance of
      trandolaprilat showed significant linear correlation (r = > 0.885, p < 0.0001)
      with CLCR after single (r = 0.879) and repeated administration (r = 0.957).
      Significantly reduced excretion of trandolaprilat was seen only when the CLCR was
      < 30 ml/min/1.73 m2. A steady state had been achieved by 7 days in all patients,
      and extrapolation suggested that this was achieved in most cases after 4 days.
      The drug was well tolerated. The effect of CRF on the pharmacokinetics and
      pharmacodynamics of trandolaprilat is of significance only when CLCR is < 30
      ml/min/1.73 m2. Hence, in these patients the standard dose should be reduced.

PMID- 7527103
TI  - Potentiation by trandolaprilat of the endothelium-dependent hyperpolarization
      induced by bradykinin.
AB  - In canine coronary arteries, bradykinin evokes endothelium-dependent relaxations
      that are mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing
      factor (EDHF). The converting-enzyme inhibitor trandolaprilat potentiates the
      endothelium-dependent relaxations evoked by bradykinin in this tissue. The
      present experiments were designed to determine whether or not facilitated release
      of EDHF contributes to the augmented response to bradykinin in the presence of
      trandolaprilat. Organ-chamber studies were performed to measure changes in
      isometric tension in rings of canine coronary arteries. In the presence of nitro
      L-arginine, an inhibitor of NO synthase, trandolaprilat augmented the endothelium
      dependent relaxations evoked by bradykinin. These relaxations were not inhibited
      by the K(+)-channel inhibitors tetraethylammonium, 4-aminopyridine, or
      glibenclamide, but were abolished in high-potassium solution. The membrane
      potential in individual smooth-muscle cells of coronary artery was measured by
      means of glass microelectrodes. Trandolaprilat potentiated the endothelium
      dependent hyperpolarizations evoked by a subthreshold concentration of
      bradykinin, and these endothelium-dependent hyperpolarizations were inhibited by
      high-potassium solution. These experiments demonstrate that EDHF contributes to
      the relaxation evoked by bradykinin in the canine coronary artery and that
      trandolaprilat potentiates the release of this factor. This effect of
      trandolaprilat may contribute to its vasodilator properties.

PMID- 7527105
TI  - Effects of trandolapril on 24-h ambulatory blood pressure in patients with mild
      to-moderate essential hypertension.
AB  - The effects of trandolapril on 24-h blood pressure in mild-to-moderate
      hypertensive patients of both sexes were investigated by conventional (clinic)
      and ambulatory recording in a double-blind study at two dosages, 1 mg (n = 14)
      and 2 mg (n = 13) once daily for 2 weeks. Both methods of measurement showed
      significant end-of-treatment decreases (p < 0.01 in all cases) in diastolic and
      systolic pressure in the 1- and 2-mg groups. Although intergroup differences were
      not significant, inspection of the mean changes from baseline in the eight 3-h
      periods constituting the 24-h profile showed that reductions were consistently
      greater in the 2-mg than in the 1-mg group, by 2 mm Hg diastolic blood pressure
      and 6 mm Hg systolic blood pressure. Values in the last segment of the placebo
      washout (46-48 h after the last active dose) showed that these reductions were
      well maintained, notably in the 2-mg group, with a minimal tendency to drift
      toward pretreatment levels. No effect was observed on the normal circadian blood
      pressure rhythm. Both doses were well tolerated. In conclusion, trandolapril is
      an effective, well-tolerated antihypertensive agent for once-daily dosing at
      either 1 or 2 mg.

PMID- 7527104
TI  - Efficacy and tolerance of trandolapril (0.5-2 mg) administered for 4 weeks in
      patients with mild-to-moderate hypertension. Investigator Study Group.
AB  - This double-blind, placebo-controlled, dose-ranging study recruited 170 patients
      with mild-to-moderate hypertension from nine centers. After a 4-week, single
      blind, placebo run-in phase, patients were randomized in a double-blind fashion
      to four parallel groups that received either placebo or 0.5, 1, or 2 mg
      trandolapril for 4 weeks. Treatment was administered as a once-daily dose in the
      morning and blood pressure was measured 24 h after drug intake. The primary
      criterion of efficacy was a decrease in supine diastolic blood pressure. At the
      end of the study, the lowest dose of trandolapril that consistently produced a
      significant difference from placebo in reducing blood pressure was 1 mg (-6.6 mm
      Hg for supine diastolic blood pressure). It was effective from around 2 weeks
      onward; the 2-mg dose differed significantly from placebo from around 1 week
      onward. At the end of the study, the 1- and 2-mg doses were equally effective.
      The lowest dose tested, 0.5 mg, showed some evidence of an effect on systolic
      blood pressure and may well prove to be a useful dose in patients who are highly
      sensitive to the effect of ACE inhibition. Tolerance throughout the study was
      good for all doses tested.

PMID- 7527106
TI  - Comparison of the efficacy and safety of trandolapril and captopril for 16 weeks
      in mild-to-moderate essential hypertension. Investigator Study Group.
AB  - This multicenter international trial recruited 180 patients from 27
      investigators. After a 4-week, single-blind placebo run-in, patients were
      randomized double-blind to 16 weeks of trandolapril 4 mg o.d. or captopril 50 mg
      b.i.d. If blood pressure was not normalized at 8 weeks, hydrochlorothiazide
      (HCTZ) 25 mg was added. Morning predosing supine diastolic blood pressure (DBP)
      was the primary efficacy measurement. At 8 weeks, the intention-to-treat analysis
      showed a significant difference for supine DBP (mean +/- SEM) between the two
      groups: trandolapril -13.5 +/- 0.9 mm Hg; captopril -10.1 +/- 1.0 mm Hg (p =
      0.007). The proportion of patients whose blood pressure was normalized was 61%
      for trandolapril and 44% for captopril (p = 0.02). At 8 weeks, 26% of the
      trandolapril group received HCTZ compared with 38% taking captopril. The addition
      of HCTZ further increased the antihypertensive effect in patients who had shown
      only moderate reductions in blood pressure after drug monotherapy. Both
      treatments were well tolerated clinically and biochemically. Withdrawals owing to
      adverse events were three from trandolapril and eight from the captopril group.
      Trandolapril given once daily is an effective and well-tolerated antihypertensive
      agent that, in this study, exhibited better efficacy compared with captopril.
      When blood pressure is not sufficiently controlled with monotherapy, the
      combination of trandolapril and HCTZ enhances the antihypertensive effect.

PMID- 7527107
TI  - Double-blind comparison of the efficacy and safety of trandolapril 2 mg and
      hydrochlorothiazide 25 mg in patients with mild-to-moderate essential
      hypertension. Investigator Study Group.
AB  - This multicenter international trial recruited 205 patients from 16
      investigators. After a 4-week, single-blind placebo run-in, patients were
      randomized to receive 16 weeks of trandolapril 2 mg/day (68 patients),
      hydrochlorothiazide (HCTZ) 25 mg/day (68 patients), or the combination (69
      patients). Morning predosing supine diastolic blood pressure (DBP) was the
      primary efficacy measurement. Intention-to-treat analysis showed significant
      decreases in all three groups in mean (+/- SEM) supine DBP throughout the study,
      with no significant differences at week 16 between trandolapril (-10.6 +/- 1.3 mm
      Hg) and HCTZ (-10.9 +/- 1.3 mm Hg). The combination gave a significantly greater
      reduction than either drug alone (-15.1 +/- 1.13 mm Hg). Blood pressure was
      normalized in the combination group in 67% of patients, a significantly higher
      proportion than either trandolapril (63%) or HCTZ (60%; p = 0.04). Each treatment
      was well tolerated. The incidence of adverse events was similar in all three
      groups. Trandolapril 2 mg once daily is an effective antihypertensive agent,
      comparable to HCTZ. Furthermore, the combination of the two drugs was shown to
      enhance the antihypertensive effect of the two compounds alone.

PMID- 7527108
TI  - Comparison of the efficacy and safety of trandolapril and nifedipine SR in mild
      to-moderate hypertension. Investigator Study Group.
AB  - After a single-blind, 4-week placebo run-in period, 161 patients were randomized
      to trandolapril 2 mg once daily (n = 54), nifedipine slow-release (SR) 20 mg
      twice daily (n = 55), or a combination of both drugs (n = 52) for 16 weeks.
      Morning predosing supine diastolic blood pressure (DBP) was the primary efficacy
      measurement. After 16 weeks the intention-to-treat analysis showed no significant
      difference in supine DBP (mean +/- SEM) between trandolapril (-12.4 +/- 1.5 mm
      Hg) and nifedipine SR (-15.3 +/- 1.4 mm Hg; p = 0.1). However, the combination
      therapy was more effective (-18.9 +/- 1.3 mm Hg). Normalized blood pressure at 16
      weeks was seen with 54% on trandolapril, 63% on nifedipine SR, and 77% on the
      combination. Adverse events, possibly related to drug, were more common with
      nifedipine SR (34%) than with trandolapril (17%; p < 0.05), and in comparison
      with the combination (21%). Drug-related treatment emergent events, reported by
      more than 3% of patients (fatigue, palpitations, edema, migraine), were seen only
      in the nifedipine SR and combination groups. Trandolapril 2 mg proved a well
      tolerated and effective antihypertensive agent, comparable to nifedipine SR 40
      mg. Furthermore, the combination of the two drugs was shown to enhance the
      antihypertensive effect of the two compounds alone. Adverse events were less
      common with trandolapril and the combination than with nifedipine SR alone.

PMID- 7527109
TI  - Long-term therapy with trandolapril, a new nonsulfhydryl ACE inhibitor, in
      hypertension: a multicenter international trial. Investigator Study Group.
AB  - An international trial recruited 1,049 patients from 122 investigators. After a 2
      to 4-week, single-blind placebo run-in, patients were treated unblinded for 1
      year. Therapy was started with trandolapril 2 mg once daily. The dose was
      increased to 4 mg/day if, after 1 month, blood pressure was not normalized, and
      then was combined with diuretics and/or calcium antagonists in increasing doses
      if necessary. At the cutoff point for this interim analysis. 481 patients had
      been treated for over 12 months and 960 for 3 months. At end point, trandolapril
      produced a significant decrease in blood pressure (-14 mm Hg for mean supine
      diastolic blood pressure). Blood pressure was normalized in 60% of the population
      with monotherapy. Trandolapril, alone or in combination with diuretics or calcium
      antagonists, was well tolerated clinically and biochemically. Only 3.9% patients
      reported dry cough. Withdrawals of patients from the study for treatment related
      reasons were 3.8%. Trandolapril had also an excellent antihypertensive effect and
      was well tolerated in elderly patients, in patients with glucose intolerance, and
      in patients with renal dysfunction.

PMID- 7527110
TI  - Pulmonary function thirteen to twenty-six years after repair of tetralogy of
      Fallot.
AB  - Lung function was evaluated in 68 patients 13 to 26 (median 19) years after
      repair of tetralogy of Fallot. Age at repair was 7 years (9 months to 42 years)
      and 51% had a palliative shunt. An outflow patch was inserted in 56%. Median
      vital capacity was 84% of predicted, forced expiratory volume in 1 second 83%,
      maximal voluntary ventilation at 40 breaths/min 70%, and diffusing capacity for
      carbon monoxide 77% of predicted. Scintigraphy demonstrated abnormal pulmonary
      perfusion in 86%. Average right lung perfusion was 57% (predicted 52%). Regional
      hypoperfusion could in some patients be explained by previous palliative shunt,
      pulmonary artery obstruction, or presence of aortopulmonary collaterals. Median
      symptom-limited work capacity was 82% (95% confidence limits 78% to 90%) of
      predicted. Twenty-eight physically active patients had high values for symptom
      limited work capacity, vital capacity, forced expiratory volume in 1 second, and
      maximal voluntary ventilation at 40 breaths/min compared with those of inactive
      patients. Lung function variables were related to physical exercise and previous
      palliative shunt. Moderate or severe pulmonary valve incompetence had negative
      but not significant influence on lung function. There was no significant
      influence of acyanosis before repair, use of transannular patch, duration of
      follow-up, or smoking. We found moderately reduced work capacity and lung
      function late after repair of tetralogy of Fallot that did not cause symptoms.
      Lung function variables were high in young active male patients and low in
      patients with previous palliative shunt. A better lung function in active
      patients indicates that physical activity should be encouraged after repair of
      tetralogy of Fallot.

PMID- 7527111
TI  - Rapid visualization of viable and nonviable endothelium on cardiovascular
      prosthetic surfaces by means of fluorescent dyes.
AB  - Increasing interest in endothelialization of synthetic and tissue cardiovascular
      prostheses in vitro emphasizes the need for simple and rapid methods to evaluate
      presence of endothelium on surfaces. Scanning electron microscopy is a commonly
      used method for this purpose. In this study we investigated alternative and more
      rapid staining methods. Human saphenous vein endothelial cells in culture and on
      cardiovascular prosthetic materials (pyrolytic carbon, cusps of bioprosthetic
      heart valves, pig aorta, and expanded polytetrafluoroethylene) were labeled by
      exposing them to medium containing 5-chloromethylfluorescein diacetate or 1,1
      dioctadecyl-3,3,3',3'-tetramethylindo carbocyanine perchlorate. For comparison,
      specimens were also fixed and processed for scanning electron microscopy. A
      bright fluorescence of endothelial cells labeled with 5-chlormethylfluorescein
      diacetate or 1,1-deoctadecyl-3,3,3',3'-tetramethylindo carbocyanine perchlorate
      wre clearly visualized in culture, on pyrolytic carbon, and on expanded
      polytetrafluoroethylene. Unfixed, prelabeled cells could be visualized
      immediately and unlabeled cells could be investigated for viability within 1
      hour. Cells seeded on biologic tissue specimens could be visualized within 15
      minutes with a modified hematoxylin-eosin staining. We suggest the use of these
      methods for rapid visualization of endothelium present on surfaces of
      cardiovascular prosthetic materials where they can partly replace the use of
      scanning electron microscopy.

PMID- 7527112
TI  - Comparison of the effects of aprotinin and tranexamic acid on blood loss and
      related variables after cardiopulmonary bypass.
AB  - Aprotinin reduces blood loss after cardiopulmonary bypass, but may sensitize
      recipients and is expensive. Tranexamic acid, a synthetic antifibrinolytic, has
      less disadvantages, but opinions differ regarding its efficacy. We studied three
      groups of patients undergoing cardiopulmonary bypass for coronary disease:
      recipients of aprotinin (total dose 4.2 x 10(6) kallikrein inhibiting units, n =
      14), recipients of tranexamic acid (total dose 20 mg/kg body weight, n = 15), and
      nonmedicated controls (n = 14) during 24 hours after cardiopulmonary bypass.
      Compared with controls, aprotinin reduced blood loss, the number of patients
      requiring transfusions, and the mean number of transfused red cell units (all
      with p < 0.05), whereas the recipients of tranexamic acid did not differ either
      from aprotinin recipients or from controls. Aprotinin and tranexamic acid both
      mitigated the early postoperative reduction of adenosine diphosphate-induced
      platelet aggregation seen in the controls (p < 0.05). Postoperative increases of
      plasma concentrations of the prothrombin activation fragment F1 + 2 and the
      thrombin-antithrombin III complex showed an activation of intravascular
      coagulation, without any intergroup differences. The balance between
      concentrations of tissue plasminogen activator and the type 1 plasminogen
      activator inhibitor disclosed an activation of fibrinolysis, without differences
      between the groups. The concentrations of D-dimer, a breakdown product of cross
      linked fibrin, remained at baseline in the recipients of aprotinin and tranexamic
      acid but tripled in the controls (p < 0.05). By contrast, the plasma antiplasmin
      activity was equally depressed in the tranexamic acid and the control groups but
      decreased less in the recipients of aprotinin (p < 0.05). This discrepancy may
      reflect the different modes of action of the two agents, which may make aprotinin
      more efficacious than tranexamic acid in the "nonfibrinolytic" act of protecting
      platelet function against attack by plasmin during cardiopulmonary bypass.

PMID- 7527113
TI  - [A follow-up of transurethral prostatectomy. A safe method with lasting results].

PMID- 7527114
TI  - Outbreak of plague-like illness caused by Pseudomonas pseudomallei in
      Maharashtra, India.

PMID- 7527115
TI  - Risperidone for Tourette's syndrome.

PMID- 7527116
TI  - Serum concentrations of prostate specific antigen and its complex with alpha 1
      antichymotrypsin before diagnosis of prostate cancer.
AB  - Prostate cancer can be detected at an early, potentially curable stage by
      screening based on digital rectal examination and serum prostate specific antigen
      (PSA). The value of screening appears doubtful, based on high 10-year survival
      rates in selected cases of early prostate cancer, but this follow-up time may be
      insufficient. By linking the information on 21172 men who took part in a
      screening examination in Finland, 1968-73, with data from the Finnish Cancer
      Registry, 44 cases of prostate cancer diagnosed up to 1980 were identified. Serum
      samples from cancer cases and from 74 controls matched for age and time of
      sampling were assayed for PSA and its complex with alpha 1-antichymotrypsin (PSA
      ACT). With a cut-off for PSA of 2.5 micrograms/L giving 92% specificity, 95% of
      the cancers developing within the first 5 years, and 52% developing in 6-10 years
      tested positive. As a potential screening test with a 5-year interval for men
      under 65, the sensitivity would be 92% and specificity 97%. The ratio of PSA-ACT
      to total PSA was lower in controls than in patients with cancer. Using this
      ratio, we could eliminate half of the false-positive results in the range 2.5-25
      micrograms/L without loss of sensitivity. Cancer was typically diagnosed 5-10
      years after PSA exceeded 2.5 micrograms/L, and the median survival after
      diagnosis was 3.6 years. 10-year survival after drawing the sample was 71% in
      cancer cases with a PSA concentration less than 4 micrograms/L and 48% in those
      with higher concentrations. The corresponding figures at 15 years were 53% and
      27%, and at 20 years 43% and 18%, respectively. These results suggest it is
      advisable to confine screening for prostate cancer to men with a life expectancy
      of clearly more than 10 years--ie, younger men, who have the greatest chance to
      benefit from early detection.

PMID- 7527118
TI  - Bacteriophage-like particle of Rochalimaea henselae.
AB  - An extracellular particle approximately 40 nM in diameter was detected in culture
      supernatant from the fastidious bacterium Rochalimaea henselae. This particle has
      at least three associated proteins and contains 14 kbp linear DNA segments that
      are heterogeneous in sequence. The 14 kbp DNA was also present in R. henselae
      cells as an extrachromosomal element for all 14 strains tested. Despite attempts
      to induce lysis of R. henselae, plaque formation was not observed. A similar
      particle, also containing 14 kbp DNA, was observed in Bartonella bacilliformis,
      and may be analogous to a bacteriophage that has been described elsewhere for B.
      bacilliformis.

PMID- 7527117
TI  - Mechanism of action of tetanus and botulinum neurotoxins.
AB  - The clostridial neurotoxins responsible for tetanus and botulism are metallo
      proteases that enter nerve cells and block neurotransmitter release via zinc
      dependent cleavage of protein components of the neuroexocytosis apparatus.
      Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular
      junction and is internalized and transported retroaxonally to the spinal cord.
      Whilst TeNT causes spastic paralysis by acting on the spinal inhibitory
      interneurons, the seven serotypes of botulinum neurotoxins (BoNT) induce a
      flaccid paralysis because they intoxicate the neuromuscular junction. TeNT and
      BoNT serotypes B, D, F and G specifically cleave VAMP/synaptobrevin, a membrane
      protein of small synaptic vesicles, at different single peptide bonds. Proteins
      of the presynaptic membrane are specifically attacked by the other BoNTs:
      serotypes A and E cleave SNAP-25 at two different sites located within the
      carboxyl terminus, whereas the specific target of serotype C is syntaxin.

PMID- 7527119
TI  - Separate pathways for excision and processing of 16S and 23S rRNA from the
      primary rRNA operon transcript from the hyperthermophilic archaebacterium
      Sulfolobus acidocaldarius: similarities to eukaryotic rRNA processing.
AB  - In the hyperthermophilic archaebacterium Sulfolobus acidocaldarius, the mature
      16S and 23S rRNA are generated by processing of a 5000-nucleotide transcript.
      Analysis of intermediates that accumulate in vivo indicates that the transcript
      contains 11 separate processing sites. The processing and maturation of 23S rRNA
      appears to follow the typical archaebacterial pathway, utilizing a bulge-helix
      bulge motif within the 23S processing helix as the substrate for an excision
      endonuclease. The precursor 23S rRNA that is released is trimmed at its 5' and 3'
      ends to generate the mature 23S rRNA found in 50S ribosomal subunits. The pathway
      for processing and maturation of 16S rRNA is distinctive and does not use the
      bulge-helix-bulge motif in the 16S processing stem. Instead, the transcript is
      cleaved at several novel positions in the 5' leader and in the 3' intercistronic
      sequence. The excised precursor 16S is trimmed at the 5' end but an extra 60
      nucleotides of what is normally spacer sequence is retained at the 3' end. The
      elongated 16S rRNA is present in active 30S subunits. An in vitro processing
      system for the 16S rRNA has been established. The RNA substrate containing the
      entire 144-nucleotide 5' leader and the first 72 nucleotides of 16S sequence is
      cleaved at the same positions observed in vivo by an endonuclease activity
      present in cell extract. These results demonstrate (i) that the 16S processing
      helix is neither utilized nor required for leader processing, and (ii) that
      complete maturation to the 5' end of 16S rRNA can occur in the absence of
      concomitant ribosome assembly and in the absence of all but the first 72
      nucleotides of the 16S rRNA sequence. The endonuclease activity responsible for
      cleavage of the 5' leader substrate is sensitive to nuclease digestion,
      suggesting that it contains an essential RNA component. The cleavage sites appear
      to be located within regions of irregular secondary structure and have a
      consensus sequence of GAUUCC.

PMID- 7527121
TI  - Encephalitis associated with cat scratch disease--Broward and Palm Beach
      Counties, Florida, 1994.
AB  - On August 14, 1994, the Broward County Public Health Unit of the Florida
      Department of Health and Rehabilitative Services was notified of three children
      from Pompano Beach who were hospitalized with encephalitis attributed to cat
      scratch disease (CSD). All three children (aged 5, 6, and 11 years) were
      previously healthy and had no histories of seizure disorders or diagnoses of CSD.
      This report summarizes the investigation of these cases.

PMID- 7527120
TI  - traJ sense RNA initiates at two different promoters in R100-1 and forms two
      stable hybrids with antisense finP RNA.
AB  - RNase protection experiments show that the sizes of the two R100 finP molecules
      are 74 and 135 nucleotides. In an RNase III mutant, finP transcripts form stable
      double-stranded hybrids of 108 bp and 68 bp with traJ transcripts. RNase
      protection experiments also show that most R100-1 transcripts originating in traM
      cross the traM-traJ intergenic region and end inside the untranslated leader
      region of traJ. Some extend into the traJ open reading frame. These findings mean
      that the antisense finP RNA, thought to regulate traJ translation, must regulate
      traJ transcripts from both J and M promoters.

PMID- 7527123
TI  - Increased low density lipoprotein receptor expression mediated through the
      insulin-like growth factor-I receptor in cultured fibroblasts.
AB  - Plasma insulin-like growth factor-I (IGF-I) levels are inversely correlated with
      apolipoprotein B and low density lipoprotein (LDL) cholesterol in humans. To
      identify a molecular basis for this observation, the effects of IGF-I on LDL
      receptor expression in fibroblasts were studied. IGF-I increased LDL receptors in
      cultured human skin fibroblasts at concentrations greater than 25 ng/ml. However,
      IGF-I effects were not easily quantitated due to secretion of inhibitory IGF
      binding proteins by the cells. To circumvent this difficulty, QAYL, an IGF-I
      analog that binds to the IGF-I receptor but not to IGF-binding proteins, was
      used. QAYL increased LDL receptor number 56-72% with half-maximum effect at 0.6
      ng/ml. alpha-IR3, a monoclonal antibody directed toward the IGF-I receptor,
      blocked this effect. QAYL treatment increased synthesis of LDL receptor protein
      without increasing LDL receptor mRNA levels or altering protein stability. Both
      QAYL and IGF-I increased LDL receptors prominently in cells that had been treated
      with physiological amounts of LDL cholesterol. IGF-I, acting through the IGF-I
      receptor and modulated by IGF-binding proteins, may contribute to the regulation
      of LDL metabolism by increasing translation of LDL receptor message.

PMID- 7527122
TI  - The orphan nuclear receptor, steroidogenic factor-1, regulates the glycoprotein
      hormone alpha-subunit gene in pituitary gonadotropes.
AB  - Tissue-specific expression of the glycoprotein hormone alpha-subunit gene in
      pituitary gonadotropes relies on a gonadotrope-specific element (GSE), which
      binds an approximately 54-kilodalton protein termed GSE-binding protein 1
      (GSEB1). We report here that GSEB1 is the orphan nuclear receptor steroidogenic
      factor-1 (SF-1), which has been shown to be a primary regulator of steroidogenic
      enzymes in the adrenal gland and gonadal tissues. GSEB1 from alpha T3-1 pituitary
      gonadotrope cells and SF-1 from Y1 adrenocortical cells and R2C testicular Leydig
      cells display identical binding properties with both the GSE and SF-1 elements.
      Antiserum specific to the SF-1 DNA-binding domain abolishes the binding of both
      GSEB1 and SF-1 to both elements. SF-1 mRNA is found in the mouse pituitary and in
      the alpha T3-1 cell line but not in other pituitary cell lines, consistent with
      the pattern of GSEB 1-binding activity. The GSE element specifically enhances
      transcription in SF-1-containing cells. The discovery that an orphan nuclear
      receptor regulates the expression of both the gonadotropin hormones in the
      pituitary and the steroidogenic enzymes in the gonad provides a potential
      molecular mechanism for coordinate control in reproductive function, perhaps
      through an as yet unidentified endocrine ligand for SF-1.

PMID- 7527124
TI  - Epitopic analysis of the Toxoplasma gondii major surface antigen SAG1.
AB  - T and B cell epitopes of the major Toxoplasma gondii surface antigen SAG1 were
      studied following CNBr fragmentation. Three fragments, F1, F2 and F3, were
      obtained, of 19, 16.5 and 14 kDa, respectively. The positions of F1 F2 and F3
      within the SAG1 protein were identified by N-terminal sequence determination. The
      F1 fragment located on residues 125-269 contains the C-terminus, and the fragment
      F2 (residues 1-124) is located at the N-terminal region. F3 is a C-terminal
      peptide about 40 amino acids shorter than the F1 fragment (residues 165-269).
      Polyclonal antibodies obtained from infected animals or humans and a monoclonal
      anti-SAG1 antibody did not recognize either the reduced protein or the reduced
      fragments on immunoblotting. The monoclonal antibody 1E5 did not recognize
      fragment F1. Mouse IgA and IgG antibodies from infected mouse sera and intestinal
      secretions, as well as human IgG antibodies, only recognized the whole protein
      and the F1 fragment. These results suggest that the fragment F1 encompasses all B
      cell epitopes recognized on the SAG1 protein after infection with the parasite
      and that the sequence 125-165 is essential for the structural integrity of these
      B cell epitopes. Murine anti-SAG1 T cell proliferation was observed in SAG1
      immunized CBA/J mice (H-2k) and BALB/c mice (H-2d), but not in C57BL/6 mice (H
      2b). The three fragments F1, F2 and F3 were able to induce specific proliferation
      of anti-SAG1 T cells from CBA/J mice, while only the F1 and F2 fragments induced
      specific blastogenesis of anti-SAG1 T cells from BALB/c mice.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7527128
TI  - Fibroblast growth factors, proteins with a broad spectrum of biological
      activities.
AB  - The first two members of the fibroblast growth factor family of proteins were
      isolated ten years ago. The family now includes nine members. Six of them are
      biologically and structurally closely related, and often the denomination
      fibroblast growth factor family refers exclusively to them. It has become
      progressively evident that the six most similar members of the family induce
      mitogenesis in practically all mesoderm and neuroectoderm derived cells. In
      healthy animals only two of these six polypeptides have been detected, which are
      currently known as acidic and basic fibroblast growth factors, respectively.
      These two polypeptides are widely distributed in the organism. Evidence has been
      progressively accumulating that acidic and basic fibroblast growth factors show
      too, a wide assortment of hormone-like activities.

PMID- 7527127
TI  - Pressure gradients between intraluminal and extraluminal spaces may affect the
      potassium induced contraction in the rabbit's basilar arteries.
AB  - In order to investigate the different contactile effects between intraluminal and
      extraluminal vasoactive agents, we studied the contractile responses of rabbit
      basilar artery to selective intraluminal and extraluminal administration of
      potassium, serotonin and histamine in vitro. We also studied how the physical
      pressure gradients, such as hydrostatic or osmotic pressure gradients between
      intraluminal and extraluminal spaces, affect potassium-induced contraction.
      Intraluminal potassium (30 mM) induced a significantly greater contraction than
      extraluminal potassium. Serotonin (2 x 10(-7) M) and histamine (10(-5) M) applied
      intraluminally caused the same magnitude of the contraction as those applied
      extraluminally and no significant differences were noted between these
      applications. These differences in potassium-induced contraction were more
      significant when the intraluminal hydrostatic pressure was elevated by 20 mmHg.
      Contraction by either intraluminal or extraluminal potassium was significantly
      decreased when intraluminal pressure was raised by 40 mmHg. As the osmotic
      pressure gradients between the extraluminal and the intraluminal spaces were
      increased, these differences in potassium-induced contraction were decreased. Our
      findings suggest that physical pressure gradients may affect potassium-induced
      contraction in a different manner from pharmacologically-induced contraction and
      that free ions can penetrate the vascular wall by physical pressure gradients
      between the intraluminal and extraluminal spaces of cerebral artery.

PMID- 7527129
TI  - Effects of BOC-CCK-4 and L 365.260 on cortical 5-HT release in guinea-pigs on
      exposure to the elevated plus maze.
AB  - The elevated plus maze is a well-established model of anxiety, with previous
      results showing that guinea-pigs handled daily from birth exhibit behaviour in
      this test similar to rats. In the present microdialysis study exposure of the
      guinea-pig to the elevated plus maze increased extracellular 5-HT in the lateral
      prefrontal cortex. The CCK-B receptor agonist BOC-CCK-4 (10 micrograms/kg)
      produced 'anxious' behaviour and potentiated the rise in 5-HT observed on
      exposure to the X-maze. The basal release of cortical extracellular 5-HT was not
      affected by BOC-CCK-4. Pretreatment with the selective CCK-B antagonist L 365.260
      (100 micrograms/kg) antagonized both the 'anxious' behaviour and the
      neurochemical changes induced by BOC-CCK-4 while L 365.260 alone produced
      'anxiolytic' behaviour, decreased basal extracellular 5-HT and prevented the
      increase in extracellular 5-HT seen when the guinea-pigs were exposed to the X
      maze. Our results show that CCK-B receptor stimulation and blockade induce
      changes in central extracellular 5-HT levels associated with 'anxious' and
      'anxiolytic' behaviour, respectively.

PMID- 7527125
TI  - Characterization of putative small nuclear RNAs from Giardia lamblia.
AB  - Small nuclear RNAs (snRNAs), which have roles in RNA metabolism, have been found
      in all eukaryotic cells. Candidate snRNAs were identified in the primitive
      protozoan parasite, Giardia lamblia, by either immunoprecipitation of total RNA
      with antiserum directed against the 2,2,7-trimethylguanosine cap structure
      characteristic of snRNAs or by Northern hybridization with oligonucleotide probes
      complementary to snRNA consensus sequences. Isolated putative snRNAs include
      eight 2,2,7-trimethylguanosine-capped species: RNAs A through H, and one non
      2,2,7-trimethylguanosine-capped species: RNA J. Single copy genes encoding RNA D,
      RNA H and RNA J were cloned and sequenced, and the 5' end of each RNA was
      determined by primer extension analysis. Certain characteristics suggest
      tentative identification of these Giardia RNAs as nucleolar RNAs with possible
      roles in rRNA processing.

PMID- 7527126
TI  - Keratinolysis and its morphological expression in hair digestion by airborne
      fungi.
AB  - The morphological expression of keratinolysis in fungi isolated from the air of
      Torino (98 isolates belonging to 36 species) was studied. Light microscopy on
      whole material and on semithin sections, as well as scanning electron microscopy
      was used. There were 19 keratinolytically active species, with seven in the genus
      Chrysosporium (C. indicum, C. keratinophilum, C. pannicola, C. tropicum, C. an.
      Arthroderma cuniculi, C. an. Pectinotrichum llanense, C. an. Renispora
      flavissima), four in the genus Malbranchea (M. arcuata, M. fulva, M. sulphurea,
      M. st. Uncinocarpus reesii), and three in the genus Trichophyton (T.
      mentagrophytes, T. rubrum, T. terrestre). In addition there were Aphanoascus
      fulvescens, Beauveria bassiana, Geomyces pannorum v. pannorum, Gymnoascus
      umbrinus and Myceliophthora vellerea. Most of these species were capable of
      developing structures related to surface erosion and radial penetration
      contemporaneously. However Gymnoascus umbrinus, Myceliophthora vellerea, an
      isolate of C. indicum, C. tropicum and Trichophyton mentagrophytes demonstrated
      only surface erosion. Different isolates of one species can vary in their
      production of invasive structures and in degree of keratinolytic activity. Thus
      such activity, like many biochemical activities of fungi, does not appear to be a
      constant or rigorously species-specific character.

PMID- 7527130
TI  - Depletion and repletion of cortical tissue and dialysate 5-HT after reserpine.
AB  - Reserpine (5 mg/kg s.c.) was given to rats kept under a reversed light-dark cycle
      and 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA)
      determined in frontal cortex tissue and dialysate at various times after drug
      treatment. The decline and return of spontaneous locomotor activity was also
      measured. Tissue 5-HT was depleted to 16% of control values 24 hr after drug
      administration and had recovered to 61% of control after 21 days. Locomotion was
      profoundly reduced by 7 hr after reserpine but had returned to normal at 4 days.
      Dialysate 5-HT, both basal and its rise on potassium (K+) stimulation, was
      reduced at 1, 7 and 21 days after reserpine but the K+ stimulated increases (as %
      of control) did not rise above % tissue repletion, thus providing evidence
      against increased mobilization of the transmitter from the partially repleted
      vesicular stores. However, at 1 day after reserpine, basal dialysate 5-HT was
      proportionately less reduced than tissue 5-HT suggesting that release from a
      reserpine insensitive (extravesicular) pool was more effective than from the
      vesicular pool. At this time, the K(+)-stimulated rise of dialysate 5-HT was
      proportionately more reduced than tissue 5-HT. By 21 days, values converged so
      that % changes of the 3 compartments were the same suggesting that at this time
      both basal and K+ stimulated dialysate 5-HT was essentially all derived from the
      vesicular pool.

PMID- 7527131
TI  - [Comparison between low and high doses of aprotinin in heart surgery].
AB  - High dose aprotinin has been used in cardiac surgery (Royston 1987) to reduce
      post operative bleeding. A low dose aprotinin ie 2000000 KIU in the oxygenator
      prime, has been also proposed. OBJECTIVE. To evaluate postoperative losses and
      holomogous blood transfusions, in patients undergoing cardiac surgery treated
      with low and high dose aprotinin. METHODS AND MATERIALS. Ninety-nine patients,
      between January and May 1993, have randomized in 3 groups: A, high dose
      aprotinin; B, low dose aprotinin; C, control. All patients were treated with
      additional blood saving techniques routinely used in our center. Statistical
      analysis was performed by means of ANOVA and Tukey Kramer test. MAIN RESULTS.
      Five patients (3 in group A, 1 each in groups B and C) have been excluded during
      the trial. The groups resulted omogeneus and comparable. Total blood losses were
      372 +/- 159 ml in group A, 401 +/- 178 ml in group B (difference are not
      significative); the 621 +/- 255 m1 in group C are highly significative. Patients
      transfused were 18.7% in group C, 10.34% in group A and 6.20% in group B.
      CONCLUSIONS. Effects of low dose aprotinin are comparable to high dose. Further
      advantages with low dose are reduction of collateral effects and intolerance
      phenomena and a better cost benefits ratio.

PMID- 7527133
TI  - Increase in bcl-2 oncoprotein and the tolerance to ischemia-induced neuronal
      death in the gerbil hippocampus.
AB  - We studied the expression of bcl-2 oncoprotein in the gerbil hippocampus after
      transient ischemia. Immunostaining using monoclonal antibody raised against bcl-2
      oncoprotein revealed intense immunoreactivity in the CA1 area following 2 min of
      ischemia, which induced tolerance to subsequent ischemia and prevented delayed
      neuronal death (DND). Following ischemia for 5 min, however, bcl-2 oncoprotein
      immunoreactivity was decreased, reflecting neuronal death in the CA1 area.
      However, pretreatment with ischemia of 2 min that prevented DND due to subsequent
      ischemia for 5 min, showed increased immunoreactivity. On the other hand,
      following 1 min of ischemia which failed to induce tolerance, no increase in the
      bcl-2 oncoprotein was observed. The results evidenced that expression of bcl-2
      oncoprotein in the CA1 area following brief ischemia is closely related to the
      acquisition of resistance to DND.

PMID- 7527132
TI  - Developing rat pineal cells manifest potential of neuronal differentiation in
      vitro.
AB  - The pineal gland in mammals is an endocrine organ and generally does not exhibit
      neuronal characteristics. However, it is known that under culture conditions,
      cells from newborn rat pineals express properties characteristic of
      photoreceptors. Here, we studied the potential of rat pineal cells to
      differentiate into neuronal cell types using different neural markers. Three
      phenotype markers characteristic of nerve cells, i.e., intense GABA, neuron
      specific antigen (HPC-1) and microtubule-associated protein 2 (MAP2)
      immunoreactivities, were detected in the pineal culture of newborn rats.
      Expression of the respective neuronal phenotypes appears to be controlled by
      different mechanisms; in the normal culture medium containing 5.4 mM KCl,
      numerous cells were stained intensely with anti-GABA antiserum, whereas only a
      few were stained intensely either with HPC-1 or MAP2 antibody. In a culture
      medium with a high concentration of KCl (35 mM), which may induce depolarization
      of nerve cells, numerous cells became strongly positive for HPC-1 or MAP2; both
      the cell bodies and the neuritic fibers were stained positively. Since cells
      intensely immunoreactive to GABA, HPC-1 or MAP2 were not found in intact pineals
      of the rat, the present results indicate that the neuronal potency of the rat
      pineal cells is expressed only in vitro and is suppressed in vivo, and that the
      potency is lost during postnatal development. Norepinephrine at 1 microM, which
      suppresses differentiation of rhodopsin immunoreactive cells, was ineffective in
      inducing phenotypic expression of neuronal properties in the present system,
      indicating that the mechanism of suppression of neuronal properties in the intact
      pineal may be different from the one for photoreceptors.

PMID- 7527134
TI  - Role of neuropeptides in the regulation of feeding behavior: a review of
      cholecystokinin, bombesin, neuropeptide Y, and galanin.
AB  - The purpose of this report is to provide a review of four peptides
      (cholecystokinin, bombesin, neuropeptide Y, galanin) and their role in feeding
      behavior. Cholecystokinin (CCK) and bombesin (BBS) are considered satiety
      peptides, and neuropeptide Y (NPY) and galanin (GAL) have been proposed as
      appetite peptides. For the purposes of this review, satiety refers to the
      physiological cessation of feeding, and appetite refers to the drive to eat and
      exists in gradations.

PMID- 7527135
TI  - Yeast Ty1 retrotransposon: the minus-strand primer binding site and a cis-acting
      domain of the Ty1 RNA are both important for packaging of primer tRNA inside
      virus-like particles.
AB  - Reverse transcription of the yeast retrotransposon Ty1 is primed by the
      cytoplasmic initiator methionine tRNA (tRNA(iMet)). The primer tRNA(iMet) is
      packaged inside virus-like particles (VLPs) and binds to a 10 nucleotides minus
      strand primer binding site, the (-)PBS, complementary to its 3' acceptor stem. We
      have found that three short sequences of the Ty1 RNA (box 1, box 2.1 and box 2.2)
      located 3' to the (-)PBS are complementary to other regions of the primer
      tRNA(iMet) (T psi C and DHU stems and loops). Reconstitution of reverse
      transcription in vitro with T7 transcribed Ty1 RNA species and tRNA(iMet)
      purified from yeast cells shows that the boxes do not affect the efficiency of
      reverse transcription. Thus the role of the boxes on packaging of the primer
      tRNA(iMet) into the VLPs was investigated by analysing the level of tRNA(iMet)
      packaged into mutant VLPs. Specific nucleotide changes in the (-)PBS or in the
      boxes that do not change the protein coding sequence but disrupt the
      complementarity with the primer tRNA(iMet) within the VLPs. We propose that base
      pairing between the primer tRNA(iMet) and the Ty1 RNA is of major importance for
      tRNA(iMet) packaging into the VLPs. Moreover the intactness of the boxes is
      essential for retrotransposition as shown by the transposition defect of a Ty1
      element harboring an intact (-)PBS and mutated boxes.

PMID- 7527138
TI  - The 'helix clamp' in HIV-1 reverse transcriptase: a new nucleic acid binding
      motif common in nucleic acid polymerases.
AB  - Amino acid sequences homologous to 259KLVGKL (X)16KLLR284 of human
      immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) are conserved in
      several nucleotide polymerizing enzymes. This amino acid motif has been
      identified in the crystal structure model as an element of the enzyme's nucleic
      acid binding apparatus. It is part of the helix-turn-helix structure, alpha H
      turn-alpha I, within the 'thumb' region of HIV-1 RT. The motif grasps the
      complexed nucleic acid at one side. Molecular modeling studies on HIV-1 RT in
      complex with a nucleic acid fragment suggest that the motif has binding function
      in the p66 subunit as well as in the p51 subunit, acting as a kind of 'helix
      clamp'. Given its wide distribution within the nucleic acid polymerases, the
      helix clamp motif is assumed to be a structure of general significance for
      nucleic acid binding.

PMID- 7527136
TI  - Molecular cloning of cDNA encoding human DNA helicase Q1 which has homology to
      Escherichia coli Rec Q helicase and localization of the gene at chromosome 12p12.
AB  - A complementary DNA encoding DNA-dependent ATPase Q1 possessing DNA helicase
      activity, which is the major DNA-dependent ATPase in human cell extracts, was
      cloned from a cDNA library of human KB cells. The predicted amino acid sequence
      has seven consecutive motifs conserved in the RNA and DNA helicase super family
      and DNA helicase Q1 belongs to DEXH helicase family. A homology search indicated
      that helicase Q1 had 47% homology in the seven conserved regions with Escherichia
      coli RecQ protein. Three RNA bands of 4.0, 3.3, and 2.2 kilobases were detected
      in HeLa cells by Northern blotting. Analysis of the genomic DNA indicated the
      presence of a homologous gene in mouse cells. The DNA helicase Q1 gene was
      localized on the short arm of human chromosome 12 at 12p12.

PMID- 7527137
TI  - Molecular cloning and characterization of a human PAX-7 cDNA expressed in normal
      and neoplastic myocytes.
AB  - The myogenic basic helix-loop-helix proteins are essential components of the
      regulatory network controlling vertebrate myogenesis. However, determined
      myoblasts appear in the limb buds which do not initially express any member of
      this transcription factor family. In a search for potential novel regulators of
      myogenesis, a human PAX-7 cDNA was isolated from primary myoblasts. Analysis of
      the DNA-binding properties of the Pax-7 paired domain revealed that it binds DNA
      in a sequence-specific manner indistinguishable from that of the paralogous Pax-3
      protein. Each of the two proteins also binds to palindromic homeodomain-binding
      sites by cooperative dimerization. Both Pax-3 and Pax-7, which are known to
      partially overlap in their expression during development, can also efficiently
      form heterodimers on these sites and stimulate reporter gene transcription in
      transient transfection experiments which, in the case of Pax-7, is dependent on
      the transactivation function encoded by the C-terminal sequences. Thus, the
      formation of heterodimers might have important consequences for target gene
      recognition and regulation during development. PAX-7 was found to be weakly
      expressed in normal human myoblasts, while PAX-3 could not be detected in these
      cells at all. However, transcripts for either PAX-3 and/or PAX-7 were expressed
      at elevated levels in tumorigenic rhabdomyosarcoma cell lines. Hence,
      overexpression of these PAX genes may be involved in the genesis of myogenic
      tumors.

PMID- 7527140
TI  - The future of death: death in the hands of science.

PMID- 7527139
TI  - Photochemically and chemically activatable antisense oligonucleotides: comparison
      of their reactivities towards DNA and RNA targets.
AB  - Dodecadeoxyribonucleotides derivatized with 1,10-phenanthroline or psoralen were
      targeted to the point mutation (G<-->U) in codon 12 of the Ha-ras mRNA. DNA and
      RNA fragments, 27 nucleotides in length, and containing the complementary
      sequence of the 12mers, were used to compare the reactivity of the activatable
      dodecamers (cleavage of the target by the phenanthroline-12mer conjugates; photo
      induced cross-linking of psoralen-12mer conjugates to the target). The reactivity
      of the RNA with the dodecamers was weaker than that of the DNA target. With
      psoralen-substituted oligonucleotides, it was possible to obtain complete
      discrimination between the mutated target (which contained a psoralen-reactive
      T(U) in the 12th codon) and the normal target (which contained G at the same
      position). When longer Ha-ras RNA fragments were used as targets (120 and 820
      nucleotides), very little reactivity was observed. Part of the reactivity could
      be recovered by using 'helper' oligonucleotides that hybridized to adjacent sites
      on the substrate. A 'helper' chain length greater than 13 was required to improve
      the reactivity of dodecamers. However, the dodecanucleotides induced RNase H
      cleavage of the target RNA in the absence of 'helper' oligonucleotide. Therefore,
      in the absence of the RNase H enzyme, long oligonucleotides are needed to compete
      with the secondary structures of the mRNA. In contrast, formation of a ternary
      complex oligonucleotide-mRNA-RNase H led to RNAT cleavage with shorter
      oligonucleotides.

PMID- 7527142
TI  - Palliative care. Privileged position.

PMID- 7527143
TI  - Substance P immunoreactive projections to the ventral respiratory group in the
      rat.
AB  - Retrograde tracing (rhodamine beads) combined with immunohistochemistry was used
      to determine the origin of neurons containing substance P that project to the
      rostral ventral respiratory group in the rat. Double-labeled neurons (rhodamine
      beads plus substance P immunoreactivity) were found in the midline caudal raphe
      nuclei (raphe obscurus, raphe pallidus, and raphe magnus) and in the
      ventrolateral medulla in the parapyramidal region. The findings of this study
      suggest that substance P-containing neurons in the caudal raphe nuclei and
      parapyramidal region project to inspiratory neurons in the rostral ventral
      respiratory group and may therefore influence their activity.

PMID- 7527144
TI  - ELISA for the neuropeptide degrading endopeptidase 3.4.24.11 in human serum and
      leukocytes.
AB  - We describe the development of a new ELISA for the detection of neural
      endopeptidase 3.4.24.11 (NEP). Neutral endopeptidase 3.4.24.11 was determined in
      preparations of human granulocytes, mononuclear cells (MNC), and in serum. Human
      recombinant NEP was used as reference. Specificity of the mAbs was tested using
      APAAP, FACS analysis, and Western blot analysis. Lysis of the blood cells was
      performed by incubating the cells with 0.4% Tween-20 and repeated freezing
      cycles. The minimal detectable dose for recombinant NEP was 15 pg/ml. The
      recovery was 94 +/- 9%. The NEP was detectable in 15 out of 20 serum samples of
      20 volunteers (mean +/- SEM, 245 +/- 88 pg/ml, n = 20)) and in all granulocyte
      preparations (1176 +/- 138 pg/10(7) cells, n = 20)). The results were
      reproducible among replicates (CV = 3 +/- 1%, n = 40), dilutions (CV = 8 +/- 2%,
      n = 5), and assays (CV = 12 +/- 4%, n = 5). With this new ELISA, a simple and
      reproducible method for the measurement of NEP 3.4.24.11 is described.

PMID- 7527141
TI  - Palliative care. Partners in care.

PMID- 7527145
TI  - The expression of lysozyme in multiple myeloma.
AB  - Lysozyme, a hitherto myelomonocytic marker, has been previously reported as being
      raised in the sera of some myeloma patients. This fact, and the sporadical
      observation of a positive immunohistochemical lysozyme staining seen in some
      myelomas, prompted us to systematically search for an expression of lysozyme in
      both neoplastic and reactive plasma cells. A total of 74 paraffin-embedded,
      formalin-fixed, EDTA-decalcified core biopsies of newly diagnosed cases of
      plasmacytoma were immunohistochemically investigated for lysozyme expression by a
      modified avidin-biotin immunoperoxidase technique. The myelomas were
      subclassified according to their nuclear maturity into poorly differentiated
      plasmacytoma (PDP) (30 cases), moderately differentiated plasmacytoma (MDP) (24
      cases), and well differentiated plasmacytoma (WDP) (20 cases). An unexpected
      lysozyme positivity was seen in 16/74 cases, and was most prevalent in 10/30
      cases of PDP. No correlation has been detected between either lysozyme and kappa
      or lambda light chain expression, or an abnormal activity of chloroacetate
      esterase sometimes seen in myeloma. Since lysozyme has not been found in normal
      plasma cells or reactive plasmacytosis, the expression of this antigen in myeloma
      represents another example of so-called lineage infidelity, and parallels the
      previously reported abnormal expression of other myelomonocytic markers in some
      myelomas and a myeloma cell line. Apart from the unsettled prognostic impact, a
      facultative lysozyme expression in myeloma must be always considered when
      applying algorhythmic immunohistological strategies in delineating the
      histogenesis of haematopoietic or lymphatic malignancies.

PMID- 7527146
TI  - [Membranolytic activity of gradex].
AB  - The membranolytic activity of gradex towards bacterial protoplasts and human
      erythrocytes has been demonstrated. Dextran shows no such activity. The lytic
      activity of gradex towards protoplasts is much lower as compared to gramicidin S.
      The increase in gramicidin S content from 2 to 5% caused no significant changes
      in the lytic activity of gradex towards protoplasts. The reduced form of gradex
      nad no hemolytic effect on human erythrocytes up to a concentration of 300
      micrograms/ml. However, the non-reduced form of gradex af a concentration of 500
      micrograms/ml lysed from 31 to 48% of erythrocytes depending on the antibiotic
      content in the polymeric matrix.

PMID- 7527148
TI  - [Effects of natural protease inhibitors on hemostasis and serum proteolysis
      blockers in patients with pulmonary tuberculosis].
AB  - Changes in hemostasis and basic serum antiproteases (alpha 1 protease inhibitor-
      alpha 1-PI and alpha 2-macroglobulin--alpha 2-MG) were followed up in patients
      with infiltrative pulmonary tuberculosis in the destruction phase. 65 patients
      received chemotherapy in combination with contrykal inhalations, 63 patients were
      given glucocorticoid hormones and prodectin. It was found that natural protease
      inhibitors produced a marked clinical response, abated more rapidly
      thrombohemorrhagic syndrome, promoted normalization of coagulation and
      fibrinolysis. Replacement aerosol therapy with antiprotease agents reestablished
      the concentration of alpha 1-PI, but had no effect on that of alpha 2-MG. This
      may contribute to reparative processes in pulmonary tissue which ran without
      significant signs of sclerosis. The results obtained may be used by clinicians
      choosing methods of pathogenetic therapy.

PMID- 7527147
TI  - [Use of proteolytic enzyme inhibitors for stabilizing medicinal substances during
      storage].
AB  - The possibility of stabilizing medicinal preparations of protein nature using the
      inhibitor of proteolytic enzymes, contrical (Trasilol) has been studied. On long
      storage, free ammonia and products of protein fragmentation accumulated in
      protein preparations, and the degree of amidation was reduced. This led to the
      decrease in biological activity of immunoglobulins and insulin. Contrical
      produced a stabilizing effect irrespective of the nature of protein, and because
      of this may find an application in pharmacy.

PMID- 7527149
TI  - [Inclusion of labeled precursors of macromolecular compounds in the mycobacterial
      cells in the presence of DP-2 preparation].
AB  - The changes in the inclusion of 3H-phenylalanine, methyl-3H-thymidine, [2-14C]
      thymidine and [5-3H]-uridine in the cells of pathogenic M. bovis-8, opportunistic
      M. fortuitum and saprophitic M. phlei, M. B-5 were comparatively investigated in
      introduction of 0.01 and 0.10% concentrations of the drug DP-2. It is shown that
      0.10% DP-2 completely stops the radionuclides supply to the cells. It is
      suggested that the target of the drug may exist in the sphere of amino acid
      biosynthesis. The presence of DP-2 is capable of disturbing transport of
      substances to the cells.

PMID- 7527150
TI  - Multiple copy sampling: rigid versus flexible protein.
AB  - Effects of protein flexibility on multiple copy conformational sampling were
      systematically evaluated by studying the side-chain placement of Phe-14 in
      protein Zif268. The multiple copy sampling is shown to be significantly more
      efficient when a flexible but harmonically constrained protein is used instead of
      a rigid protein. A range of constraint force from 1 to 25 kcal/mol.A per atom is
      determined to be sufficient to prevent the protein from distortion while allowing
      the protein to fluctuate for enhanced sampling. The protein fluctuations are
      essential in smoothing the effective energy surface as shown by the opening
      closing of a protein hydrophobic pocket during a multiple copy energy
      minimization, a phenomenon that has been previously observed only in molecular
      dynamics. These results provide a practical guidance for applying the multiple
      copy techniques to molecular modeling and computer-aided drug design.

PMID- 7527151
TI  - Comparison of the cytotoxic and antiretroviral effects of 3-nitrosobenzamide and
      4-iodo-3-nitrobenzamide.

PMID- 7527152
TI  - Differential effects of benzodiazepines, including diazepam, clonazepam, Ro 5
      4864 and devazepide, on lindane-induced toxicity.

PMID- 7527153
TI  - Chronic immune demyelinating neuropathies.
AB  - The classification of immune-mediated demyelinating polyneuropathies has become
      more complex in recent years. Initial definitions of chronic inflammatory
      demyelinating polyneuropathy (CIDP) were often broad enough to include almost any
      acquired polyneuropathy with demyelinating features. However, subdivision of
      acquired demyelinating polyneuropathies into different categories seems justified
      because 1) several distinct clinical syndromes have been identified, 2)
      characteristic and distinctive patterns of serum antibody binding are associated
      with each specific clinical syndrome and, 3) the syndromes respond differently to
      immune modulating treatments (Table 1). Larger series and controlled trials will
      be necessary to determine the therapeutic regimens that optimize the benefit:risk
      considerations for patients with these syndromes.

PMID- 7527154
TI  - [Surgery of urinary incontinence. Role of the surgical nurse].

PMID- 7527156
TI  - Association of insulin receptor substrate-1 with integrins.
AB  - Insulin stimulation was found to promote association of the alpha v beta 3
      integrin (a vitronectin receptor) with insulin receptor substrate-1 (IRS-1), an
      intracellular protein that mediates insulin signaling by binding other signaling
      molecules, including growth factor receptor-bound protein 2 (Grb2) and
      phosphatidylinositol-3' kinase. Insulin-treated cells expressing the alpha v beta
      3 integrin showed 2.5 times more DNA synthesis when plated on vitronectin than on
      other substrates, whereas cells expressing another vitronectin receptor, alpha v
      beta 5, did not show this difference. The association between integrin and IRS-1
      may be a mechanism for the synergistic action of growth factor and extracellular
      matrix receptors.

PMID- 7527157
TI  - Stimulation and inhibition of angiogenesis by placental proliferin and proliferin
      related protein.
AB  - In many mammalian species, the placenta is the site of synthesis of proteins in
      the prolactin and growth hormone family. Analysis of two such proteins,
      proliferin (PLF) and proliferin-related protein (PRP), revealed that they are
      potent regulators of angiogenesis; PLF stimulated and PRP inhibited endothelial
      cell migration in cell culture and neovascularization in vivo. The mouse placenta
      secretes an angiogenic activity during the middle of pregnancy that corresponds
      primarily to PLF, but later in gestation releases a factor that inhibits
      angiogenesis, which was identified as PRP. Incubation of placental tissue with
      PLF led to the specific binding of this hormone to capillary endothelial cells.
      Thus PLF and PRP may regulate the initiation and then the cessation of placental
      neovascularization.

PMID- 7527155
TI  - [Treatment of benign prostatic hypertrophy by hyperthermia, ultrasonics and
      laser].

PMID- 7527159
TI  - [Early use and adequate dosage of G-csf in drug-induced agranulocytosis].

PMID- 7527158
TI  - Biochemical and ultrasound screening for chromosomal abnormalities.
AB  - The utility of ultrasound screening for Down syndrome should be judged by whether
      the pertinent markers are reliably obtained and by whether they efficiently
      discriminate between fetuses with Down syndrome and euploid fetuses. Furthermore,
      the markers must be reliable at a gestational age early enough to be clinically
      useful. Screening for characteristic congenital malformations will result in a
      low detection rate of Down syndrome, and many of these cases will be identified
      only after 24 weeks of gestation. The subtlety of many of the ultrasound findings
      of Down syndrome in the second trimester requires significant technical expertise
      if ultrasonographic screening is to be used. Investigation thus far has centered
      on identifying patients at increased risk of Down syndrome, and no data are
      available on how much a normal ultrasound might decrease the risk associated with
      advanced maternal age or abnormal biochemical screening. Biochemical screening is
      currently able to detect at least 60% of Down syndrome in a low-risk population.
      The ultimate value of ultrasound may be to help further define the risk assigned
      by age and biochemical screening, to provide each patient with an aggregate risk.
      The decision on whether or not to offer an amniocentesis could then be based on
      the findings of these various examinations, with the goal to improve the accuracy
      of age or biochemical screening alone. It remains for studies to be done to
      determine whether ultrasound can in fact decrease the prior risk, and for large
      enough series and formulas to be published that allow us to specifically define
      how to integrate the information from each screen.

PMID- 7527160
TI  - Postreceptor signal transduction mechanisms involved in octreotide-induced
      inhibition of angiogenesis.
AB  - BACKGROUND: Somatostatin analogues inhibit peptide release and cell growth
      through multiple postreceptor signal transduction mechanisms (PRSTM), including G
      proteins (GP), cyclic adenosine monophosphate (cAMP), calcium, protein kinase C
      (PKC), and tyrosine phosphatase (TP). Octreotide acetate (OA), a somatostatin
      analogue, has been shown to inhibit angiogenesis; however, the PRSTM involved are
      unknown. METHODS: Fertilized chicken eggs were obtained and incubated. On day 3,
      embryos were removed and placed in plastic wrap hammocks. On day 7, disks
      containing OA, test substances that interfere with PRSTM, or combinations of OA
      plus a test substance were placed on the developing chorioallantoic membrane.
      Blood vessel growth under each disk was assessed at 24 hours. Data were evaluated
      by chi-squared analysis. RESULTS: OA's ability to inhibit angiogenesis is
      significantly diminished when combined with calcium, bradykinin (increases
      calcium), pertussis toxin (inhibits GP), or 3-isobutyl-1-methylxanthine
      (increases cAMP). In contrast, no significant decrease is noted in OA's ability
      to inhibit angiogenesis when combined with phorbol ester (activates PKC) or
      vanadate (inhibits TP). CONCLUSIONS: OA-induced inhibition of angiogenesis is GP,
      calcium, and cAMP dependent and is PKC and TP independent. Better understanding
      of the PRSTM involved with OA-induced inhibition of angiogenesis may lead to
      enhancement of OA's effect on angiogenesis.

PMID- 7527161
TI  - [The comparative efficacy of verapamil, nifedipine and propranolol in patients
      with IHD and an enhanced risk of a fatal outcome].
AB  - In a randomized controlled trial 329 postmyocardial infarction patients with high
      grade ventricular extrasystoles were divided into 3 groups. Group 1 of 112
      patients received calcium antagonists (verapamil, nifedipine,
      verapamil+nifedipine), group 2 of 100 patients received propranolol
      hydrochloride, group 3 consisted of 117 controls. The aim of the study was to
      elucidate the effect of the above drugs on sudden death and repeated nonfatal
      infarction risk. The mean follow-up duration made up 16 +/- 0.9, 16.8 +/- 1.1,
      20.8 +/- 1.0 months for groups 1,2 and 3, respectively. 35 patients of the
      treatment groups turned out inappreciable because of early discontinuation of
      chemotherapy. Overall lethality for the groups 1, 2 and 3 reached 0.9%, 4% and
      12% of patients, respectively. Most of lethal outcomes in the controls were
      sudden. Repeated nonfatal myocardial infarction arose less frequently in groups 1
      and 2, but the difference was insignificant.

PMID- 7527163
TI  - Brevetoxin PbTx-2 immunology: differential epitope recognition by antibodies from
      two goats.
AB  - The epitopic regions of the brevetoxin PbTx-3 molecule, produced by the marine
      dinoflagellate Ptychodiscus brevis, have been identified by structural
      modification at three distinct regions of the toxin. These are: the A-ring
      lactone region of the molecule, the K-ring side-chain and the H-ring. The
      modified PbTx-3 derivatives were tested for their ability to bind brevetoxin goat
      antisera directed against the PbTx-3 molecule, by radioimmunoassay. The results
      showed that at least two major epitopes and one minor epitope are recognized: the
      A-ring lactone region of the molecule and the K-ring side-chain, and the H-ring.
      The results illustrate the variety of antibodies which may be produced, even
      within a species, and suggests that epitope characterization is important in the
      development of assays which are to be employed in seafood safety issues.

PMID- 7527162
TI  - [The characteristics of the autonomic regulation of the heart rate in patients
      with IHD and ventricular arrhythmias under obzidan therapy].
AB  - Propranolol hydrochloride was administered to 30 patients with stable angina
      pectoris suffering from coronary heart disease (CHD). Of them 18 patients had
      ventricular extrasystole, 12 had ventricular tachycardia. All the patients
      underwent resting ECG, bicycle ergometry, transesophageal pacing, 24-h ECG
      monitoring. Vegetative cardiac regulation was determined using mathematical
      analysis of at least 100 successive intervals R-R at rest before and after
      therapy (120 mg day of propranolol hydrochloride). The authors estimated
      characteristics of the variance analysis and two secondary values--stress index
      and centralization index calculated by spectral characteristics of the rhythm.
      Only in CHD patients with ventricular tachycardia the treatment shifted the
      vegetative tone in the direction of parasympathetic nervous system. It is
      concluded that propranolol hydrochloride affects cardiac rhythm depending on the
      initial condition of vegetative regulation of cardiac activity.

PMID- 7527164
TI  - Effect of 11 beta-substituents on the regioselective chlorination of estrogens
      with 2,3,4,5,6,6-hexachloro-2,4-cyclohexadienone.
AB  - The reaction of 11 beta-substituted estrogens with 2,3,4,5,6,6-hexachloro-2,4
      cyclohexadienone affords exclusively ortho-substituted monochlorinated products
      including a major 4-chloro and a minor 2-chloro derivative. In the absence of an
      11 beta-substituent, regioselectivity is lost, resulting in a mixture of 10 beta-
      and ortho-chlorinated products.

PMID- 7527165
TI  - Beta-structure in the membrane-spanning part of the nicotinic acetylcholine
      receptor (or how helical are transmembrane helices?).
AB  - The 'four-transmembrane-helix receptors' transmit their signals from the
      extracellular space to the cytoplasm via an intramembrane domain. In the case of
      the nicotinic acetylcholine receptor this domain comprises an ion channel formed
      by homologous secondary structure elements in the receptor subunits. It was
      believed to be exclusively alpha-helical, but recent experimental evidence
      questions the widely accepted model: beta-strands seem to be part of the membrane
      spanning domain.

PMID- 7527166
TI  - Natural history of prostatism: impact of urinary symptoms on quality of life in
      2115 randomly selected community men.
AB  - OBJECTIVES: To assess the impact of urinary symptoms on health-related quality of
      life (QoL), including degree of bother, worry, interference with daily
      activities, psychological well-being, sexual function, and general health in a
      community-based cohort of men. METHODS: Eligible white men (n = 2115) aged 40 to
      79 years who had not undergone previous prostate surgery or had prostate cancer
      were randomly selected from county residents. These subjects completed a
      questionnaire, which asked them about frequency and bother of urinary symptoms,
      interference with daily activities, psychological well-being, worry about
      urologic disease, sexual functioning, and general health. RESULTS: Men with
      moderate to severe voiding symptoms reported, on average, four to six times the
      degree of bother and interference with daily activities and twice the level of
      worry of men with mild symptoms. Nearly five times the degree of bother and
      interference was reported for those with mild than with no symptoms. A higher
      percentage of men with moderate to severe symptoms (26% to 33%) than mild
      symptoms (< 8%) reported limiting fluids before bed, travel, or driving 2 hours.
      Receiver operating characteristic curves support the recommended symptom index
      cutpoint for moderate symptoms (= 8) by differentiating men with and without
      bother, interference with daily living, or dissatisfaction with urinary
      condition. CONCLUSIONS: Moderate to severe urinary symptoms have a significant
      impact on men's lives in terms of degree of bother, worry, interference with
      daily living, and psychological well-being. The recommended cutpoint on symptom
      index differentiates men with and without decrement in health-related quality of
      life.

PMID- 7527167
TI  - Identification of insignificant prostate cancers: analysis of preoperative
      parameters.
AB  - OBJECTIVES: Analyzing preoperative parameters to help determine the risk of a
      random or systematic prostate needle biopsy specimen detecting an incidental
      microscopic prostate cancer. METHODS: We reviewed the charts of 28 patients who
      had < or = 3 mm of Gleason grade (Glgr) < or = 2 (score < or = 4) prostate cancer
      in their prostate biopsy specimen and subsequently underwent a radical retropubic
      prostatectomy (RRP). Histopathologic review of the RRP specimen was carefully
      performed to determine the respective tumor volume, number of tumor foci,
      pathologic stage, Glgr, and score. Prostate-specific antigen (PSA) levels and the
      calculated PSA density (PSAD) were recorded for each case. RESULTS: Sixteen of
      the 28 (57%) RRP specimens contained a very small well-differentiated tumor (< or
      = 0.2 cc); 7 (25%) tumors were minimally larger (0.2 to 0.5 cc); and 2 specimens
      (7%) contained a large tumor (4 and 6 cc) only sampled by the biopsy specimen.
      Mean PSA levels and PSAD values both significantly differentiated tumors < or =
      0.5 cc from those > 0.5 cc (p < 0.005). PSA < or = 4 vs PSAD < or = 0.1 correctly
      identified 12 of 23 (52%) vs 22 of 23 (96%) tumors < or = 0.5 cc, and 10 of 16
      (63%) vs 15 of 16 (94%) tumors < or = 0.2 cc, respectively; both parameters
      excluded 4 of 5 (80%) tumors > 0.5 cc. PSA < or = 4 vs PSAD < or = 0.1 identified
      13 of 25 (52%) vs 24 of 25 (96%) organ-confined tumors, respectively, and both
      parameters excluded the 2 specimen-confined and 1 margin-positive tumors. Thus,
      PSAD had an excellent ability to differentiate the tumors based on their volumes.
      All tumors < or = 0.5 cc in the RRP specimen were organ-confined and
      postoperative serial PSA levels remained < 0.4 in these patients at a mean follow
      up of 24 months. CONCLUSIONS: Our data indicate that a patient who has a random
      or systematic prostate biopsy specimen that contains < or = 3 mm of Glgr < or = 2
      prostate cancer and a PSAD < or = 0.1 is at a substantial risk (82%) of being
      diagnosed with an incidental, organ-confined, and probably insignificant,
      microscopic prostate cancer.

PMID- 7527168
TI  - Significance of tumor angiogenesis in clinically localized prostate carcinoma
      treated with external beam radiotherapy.
AB  - OBJECTIVES: To determine the prognostic significance of microvessel density (a
      measure of tumor angiogenesis) in comparison with other prognostic factors for
      patients with clinically localized prostatic carcinoma treated with external beam
      radiotherapy. METHODS: Microvessel density was quantified within the initial
      invasive carcinoma from the diagnostic transurethral resection specimen of 25
      patients with a mean follow-up of 44 months. Microvessels were identified by
      immunohistochemical staining of endothelial cells for factor VIII-related antigen
      in formalin-fixed, paraffin-embedded tissue. Microvessels were counted in a x200
      field (0.754 mm2) in the area of maximal angiogenesis. RESULTS: Microvessel
      density correlated with several pretreatment prognostic factors, including
      prostate-specific antigen (PSA) (p < 0.0001), tumor grade (p = 0.006), and ploidy
      (p = 0.016). The degree of tumor angiogenesis also correlated with outcome
      following external beam radiotherapy. The mean microvessel count in the nine
      tumors from patients who failed radiotherapy (ie, had rising PSA and/or clinical
      relapse) was 97.0 +/- 33.6 (+/- SD) per x200 field compared with 46.1 +/- 17.1
      for the 16 patients with no evidence of failure (p < 0.0001). Increased
      microvessel density was also associated with a significantly worse actuarial
      outcome at 4 years using either biochemical relapse (rising PSA) or a composite
      endpoint of rising PSA or clinical relapse (p = 0.0003). CONCLUSIONS: The
      intratumoral quantification of tumor angiogenesis may prove valuable as a
      prognostic indicator in patients with clinically localized prostate cancer
      treated with radiotherapy.

PMID- 7527169
TI  - Impact of bladder neck preservation during radical prostatectomy on continence
      and cancer control.
AB  - OBJECTIVES: To assess the effect of preservation of the bladder neck and other
      factors on the rate of postoperative urinary continence and cancer control after
      radical prostatectomy. METHODS: Prospective analysis of clinical and pathologic
      findings in 206 consecutive patients undergoing radical prostatectomy with a
      surgical technique that emphasizes preservation of periurethral supporting
      tissue, urethral length, incorporation of the posterior periurethral fascia into
      the vesicourethral anastomosis, and preservation of the bladder neck. RESULTS:
      Uni- and multivariate statistical analysis demonstrated that patient age (p =
      0.033) and vesical neck contracture (p = 0.047) were predictive of incomplete
      return of urinary control. Preservation of the vesical neck had no impact on
      return of continence, but was associated with a trend to a lower incidence of
      vesical neck contractures. A positive bladder neck margin occurred in 6.8% of
      surgical specimens and was associated with a higher grade, more advanced local
      stage, and other positive margins in all cases. The rate of local recurrence or
      prostate-specific antigen (PSA)-only failure was similarly independent of whether
      the vesical neck was preserved or resected and reconstructed. CONCLUSIONS: Age
      greater than 65 and occurrence of a vesical neck contracture are adverse
      predictors for return of urinary continence after radical prostatectomy.
      Preservation of the bladder neck does not have an impact on return of urinary
      control but may be associated with a lower risk of vesical neck contracture.
      Preservation of the bladder neck does not compromise cancer control as assessed
      by local or PSA-only failure rates.

PMID- 7527171
TI  - Autonomic innervation of the airways.
AB  - A review is given of the literature concerning the autonomic innervation of
      airway smooth muscle. The cholinergic, adrenergic and non-cholinergic non
      adrenergic (NANC) systems in humans and several animal species are discussed. The
      diagnostic and therapeutic possibilities and limitations of new receptor specific
      agonists and antagonists are also discussed.

PMID- 7527170
TI  - Lomefloxacin prophylaxis in visual laser ablation of the prostate.
AB  - OBJECTIVES: Visual laser ablation of the prostate (VLAP) is a relatively new
      option for relief of urinary outlet obstruction secondary to benign prostatic
      hyperplasia. There is currently no consensus regarding the optimum use of
      antibiotic prophylaxis in VLAP. This study was designed to evaluate two dosage
      regimens of a new difluoroquinolone, lomefloxacin, for prevention of
      postoperative bacteriuria following VLAP. METHODS: Sixty men with benign
      prostatic hyperplasia who were scheduled for VLAP were enrolled in an open-label,
      randomized trial comparing groups receiving no antimicrobial prophylaxis (n =
      20), a single preoperative oral dose of 400 mg lomefloxacin (n = 20), or a single
      preoperative oral dose of 400 mg lomefloxacin followed by 400 mg daily for 3 days
      (n = 20). The VLAP procedures were performed using 60 watts of energy from a
      neodymium:yttrium-aluminum-garnet (Nd:YAG) laser delivered via a Bard Urolase
      fiber or Laser Sonic fiber. RESULTS: Ten of 20 patients (50%) in the no
      prophylaxis group developed bacteriuria (defined as growth of 10(4) or more
      colony-forming units/mL) during the 14 days following surgery, whereas 2 of 20
      patients (10%) in the single-dose group and 1 of 20 in the multiple-dose group
      (5%) developed bacteriuria during the follow-up period. Both dosage regimens were
      well tolerated. CONCLUSIONS: Lomefloxacin was successful in preventing
      postoperative bacteriuria in 90% (single dose) to 95% (multiple doses) of
      patients undergoing VLAP. There was no clinically significant difference between
      the two dosage regimens.

PMID- 7527172
TI  - Haematology and biochemistry reference values for sows kept under modern
      management conditions.
AB  - The data presented here were obtained using blood samples from 159 healthy,
      conventionally managed sows from 37 breeding herds. Sows were sampled at weaning
      and at 4-5 weeks gestation. Paired blood samples were analysed from sows that had
      a normal pregnancy and subsequently farrowed. The mean values of serum total
      protein, albumin and gamma globulin concentration were lower in the blood samples
      obtained at weaning compared with those obtained at 4-5 weeks gestation.
      Leucocyte count was higher, mostly as a result of a higher segmented neutrophil
      count, in the blood samples obtained at weaning compared with those obtained at 4
      5 weeks gestation.

PMID- 7527173
TI  - Complementation of human immunodeficiency virus type 1 vif mutants in some CD4+ T
      cell lines.
AB  - The viral infectivity factor gene, vif of human immunodeficiency virus type 1
      (HIV-1), is required for full infectivity in most T-cell lines. The replication
      kinetics exhibited by these mutants has been shown to be cell type-dependent. In
      H9 cells as well as primary lymphocytes, vif mutants are incapable of
      establishing infection. This has led to classification of these cell types as non
      permissive for vif mutant replication. The T-cell lines Sup T1 and C8166 are able
      to replicate the vif mutant virus, leading to their classification as permissive
      for vif mutant replication. In this study, four cell lines (Sup T1, C8166, Molt 4
      Clone 8, and A3.01) were tested for their ability to replicate vif mutant virus
      derived from two different strains of HIV-1 (HXB2 and NL4-3) that had been
      passaged on various cell lines. Although the kinetics of initial infection was
      delayed in all cells, by the second passage of vif mutant virus on Sup T1 or Molt
      4 cells the kinetics of replication were identical to wild type virus. In
      contrast, mutant virus displayed delayed replication kinetics in C8166 and A3.01
      cells in both initial and subsequent passages. In addition, the levels of viral
      DNA in infected Sup T1 cells were similar for delta vif and wild type virus, but
      in C8166 cells delta vif virus DNA levels were reduced compared to wild type
      virus. These results argue that in Sup T1 and Molt 4 cells there is a factor
      present that is able to complement the defect in vif mutant viruses which is
      absent or inefficient in its activity in C8166 and A3.01 cells.

PMID- 7527174
TI  - Antibacterial susceptibility of bovine-mastitis pathogens tested directly in milk
      from infected quarters.
AB  - Antibacterial susceptibilities of bovine-mastitis pathogens were analysed
      directly in 57 mastitic milk samples without inoculation with exogenous
      organisms. Aseptically collected milk was mixed with serial dilutions of
      antibacterials and the growth was observed using 2,3,5-triphenyltetrazolium
      chloride (TTC) reduction the following day. The results were compared with those
      obtained by using calibrated bacterial inocula in turbidimetric minimum
      inhibitory-concentration (MIC) determination in broth cultures, and in TTC-broth
      culture-test and TTC-normal milk-test. The results of different methods all
      correlated positively when the entire data was used. However, taking the direct
      test in mastitic milk as the 'true' result, the total discrepancies varied from
      34.7% to 48.8%. Antibacterial activities of the trimethoprim-sulphadoxine
      combination, and of spiramycin and ampicillin, decreased significantly when
      nutrient broth was replaced by milk as the test medium. The efficacy of
      trimethoprim-sulphadoxine as an antibacterial agent was also dependent on the
      source of milk.

PMID- 7527175
TI  - Peripheral blood progenitor cell transplantation estimated by three-colour (CD34,
      HLA-DR, CD33) flow cytometry.
AB  - The relationships between transfused cell number of CD34+ cell subpopulations
      divided by HLA-DR and CD33 antibodies and hematopoietic recovery patterns after
      peripheral blood progenitor cell transplantation (PBPCT) subsequent to
      myeloablative chemoradiotherapy were investigated in 14 children with cancer.
      Both logarithm of transfused CD34+ cell number/10(6)/kg and logarithm of
      transfused cell number/10(6)/kg of the CD34+HLA-DR+CD33+ subpopulation, which is
      supposed to be myeloid-committed cells, were correlated with myeloid recovery
      after PBSCT, though they were not correlated with erythroid or platelets
      recovery. On the other hand, logarithm of transfused cell number/10(6)/kg of CD34
      + HLA-DR-CD33-subpopulation, which is supposed to be immature progenitor cells,
      was not correlated with myeloid recovery but correlated with erythroid recovery
      and platelet recovery. These results suggested that rapid myelopoiesis after
      PBPCT occurs following transfusion of sufficient numbers of myeloid-committed
      cells and complete hematopoietic reconstitution occurs after transfusion of
      sufficient numbers of immature hematopoietic progenitor cells.

PMID- 7527176
TI  - Expression of basic fibroblast growth factor, nerve growth factor, platelet
      derived growth factor and transforming growth factor-beta in human brain abscess.
AB  - We correlated the histopathological findings of six human brain abscesses with
      the expression of basic fibroblast growth factor (bFGF), nerve growth factor
      (NGF), platelet-derived growth factor (PDGF) and transforming growth factor-beta
      (TGF beta). The clinical courses ranged from 1 month to 1 year and viridans
      streptococcus was the major pathogen. In early abscesses, we demonstrated strong
      bFGF and moderate NGF and PDGF immunoreactivities in neutrophils and
      monocytes/macrophages infiltrating the abscess wall and in the fibrin layer
      lining the abscess center. In the subacute cases, growth of capillaries and
      fibroblasts into the fibrin layer and deposition of collagen resulted in the
      formation of a mesodermal layer between the abscess center and the outer gliotic
      layer. The proliferative non-neural cells (endothelial cells, fibroblasts and
      glial cells) expressed mild to strong bFGF, NGF and PDGF immunoreactivities,
      while strong TGF beta staining was seen in the extracellular matrix. A loss of
      growth factor expression and increased fibrosis was seen in the chronic case.
      These findings suggest that bFGF, NGF, PDGF and TGF beta produced by the
      continued influx of leukocytes and by the proliferating non-neural cells may
      mediate various steps of defense mechanisms and wound healing such as
      angiogenesis, fibrogenesis and gliosis.

PMID- 7527177
TI  - Breast mucin and associated antigens in diagnosis and therapy.

PMID- 7527178
TI  - Specificity of the IgG response in mice and human breast cancer patients
      following immunization against synthetic sialyl-Tn, an epitope with possible
      functional significance in metastasis.
AB  - Several investigators have shown that the expression of the sialyl-Tn (STn)
      epitope on cancer associated mucins is associated with a poor prognosis in
      several human cancers suggesting that STn may have functional significance in
      metastasis. We postulate that antibodies against the STn-epitope can inhibit
      metastasis. We generated a synthetic "mimic", NANA alpha (2-->6)GalNAc alpha-O
      Crotyl (STn-crotyl), of the natural O-linked epitope on mucins, NANA alpha (2-
      >6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier
      protein KLH through the crotyl linker arm and a "vaccine" containing STn-KLH plus
      Detox adjuvant was formulated. The immunogenicity of the vaccine was evaluated in
      BALB/c mice and in metastatic breast cancer patients. The specificity and titres
      of IgG antibodies were evaluated by ELISA on ovine submaxillary mucin (OSM) solid
      phases. OSM is a convenient source of repeating, natural O-linked STn-serine
      structures. Mice immunized three times with as little as 0.25 microgram of STn
      KLH produced a median IgG titre of over 1:5000 on solid phase OSM. Anti-OSM IgG
      monoclonal antibodies generated from these mice were completely inhibited in
      their binding to solid phase OSM equally well by STn-serine and STn-crotyl
      synthetic haptens but not by several other closely related synthetic haptens.
      Breast cancer patients immunized 2-8 times with 25 or 100 micrograms of the same
      vaccine produced median peak IgG titres 1:1280 measured on STn-HSA and 1:80 on
      OSM. Once again, hapten inhibition experiments with the human sera demonstrated
      the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not
      against several other related synthetic haptens. We found little or no evidence
      that the artificial linker arm (crotyl linker) contributed significantly to
      either the titre or affinity of the antibodies generated in either mice or human
      breast cancer patients. This suggests that the antibodies recognized the cancer
      associated disaccharide NANA alpha (2-->6)GalNAc. Evidence of a clinical response
      was noted in several of the immunized breast cancer patients with other patients
      showing prolonged disease stability.

PMID- 7527179
TI  - Overview of radioimmunotherapy in advanced breast cancer using I-131 chimeric L6.
AB  - 131I chimeric L6 (ChL6) monoclonal antibody (MoAb) therapy has been performed in
      12 patients with advanced, metastatic breast cancer. The protocol was designed to
      determine the maximum tolerated dose (MTD) of radioimmunotherapy that could be
      administered at 4 intervals. Ten patients received 20-70 mCi/m2 of 131I ChL6. Two
      of the patients received granulocyte colony stimulating factor (GCSF) on days 10
      20 post therapy. The MTD for two doses was 60 mCi/m2 and thrombocytopenia was the
      dose limiting toxicity in the absence of marrow reconstitution with stem cells.
      Two patients received 150 mCi/m2 with autologous peripheral blood stem cell
      support 7 and 9 days post treatment. The MTD has not been reached for 131I-ChL6
      with autologous stem cell support. In the 12 patients treated with 131I ChL6, six
      patients (50%) had measurable tumor regressions greater than 30% of the sum of
      the largest two dimensional products for measurable tumors. Four of these 6
      patients had a partial response (PR), i.e., > or = 50% reduction in tumor size.
      These therapeutic responses associated with modest clinical toxicity in heavily
      pretreated patients suggest that clinically relevant radioimmunotherapeutic
      approaches can be devised for metastatic breast cancer.

PMID- 7527180
TI  - Peptide epitopes in breast cancer mucins.

PMID- 7527182
TI  - Obesity and benign prostatic hyperplasia.
AB  - Abdominal obesity increases the estrogen-to-androgen ratio and may increase
      sympathetic nervous activity, both hypothesized to influence the development of
      benign prostatic hyperplasia and the severity of urinary obstructive symptoms. In
      1986 and 1987, men aged 40-75 years who were participants in the Health
      Professionals Follow-up Study and who were without prior diagnosis of cancer or
      prostatectomy provided data on weight, height, and waist and hip circumferences.
      The men were followed for incidence of prostatectomy for benign prostatic
      hyperplasia up to January 1992. In addition, the frequency and severity of
      symptoms of urinary obstruction were assessed among respondents to a
      questionnaire in 1992. Among 25,892 men who provided complete information for
      both surgery and symptoms, 837 men had surgery for benign prostatic hyperplasia,
      and 2,581 of those without surgery reported frequent urinary symptoms. After
      adjustment for age, smoking, and body mass index, abdominal obesity was related
      to prostatectomy (odds ratio (OR) = 2.38, 95% confidence interval (CI) 1.42-3.99,
      for those with a waist circumference > or = 43 inches (109 cm) relative to those
      with a waist circumference < 35 inches (89 cm); p trend < 0.0001) and with
      frequent urinary symptoms among those without prostatectomy (OR = 2.00, 95% CI
      1.47-2.72; p < 0.0001). Body mass index, hip circumference, and waist-to-hip
      ratio were not associated with benign prostatic hyperplasia independently of
      waist circumference. These results suggest that abdominal obesity in men may
      increase the frequency and severity of urinary obstructive symptoms and may
      increase the likelihood that such obese men will undergo a prostatectomy.

PMID- 7527181
TI  - Neutrophil activation after percutaneous transluminal coronary angioplasty.
AB  - We investigated whether percutaneous transluminal coronary angioplasty (PTCA)
      would induce neutrophil activation in patients with coronary artery disease.
      Blood samples were taken from the coronary sinus in 14 patients who underwent
      PTCA and in 9 control subjects who underwent coronary arteriography (CAG). Flow
      cytometry was used to measure membrane surface expression of beta 2 integrin
      (CD11b) and the generation of hydrogen peroxide in neutrophils after ex vivo
      phorbol myristate acetate stimulation by 2,'7'-dichlorofluorescein. Neutrophil
      elastase was measured by an immunoenzymatic method. Surface expression of CD11b
      increased significantly, approximately twofold, after PTCA but not after CAG.
      Mean fluorescence intensity of 2',7'-dichlorofluorescein in stimulated
      neutrophils decreased significantly after PTCA, suggesting a previous in vivo
      activation, but not after CAG. Neutrophil elastase increased significantly after
      PTCA but not after CAG. These data indicate that PTCA induces neutrophil
      activation and suggest that neutrophils may contribute to the ischemic injury.

PMID- 7527183
TI  - Effects of aprotinin on complement and granulocyte activation during ex vivo
      hemodialysis.
AB  - Hemodialysis with cellulosic membranes results in complement activation,
      granulocytopenia, and granulocyte activation. To further investigate the
      relationship between complement activation and granulocyte activation, we
      developed a model of ex vivo hemodialysis with blood flow, dialysate flow, and
      dialysate composition similar to in vivo hemodialysis. We used this model to
      investigate the effects of aprotinin, a potent serine protease inhibitor
      frequently used as an anti-inflammatory agent during cardiopulmonary bypass
      surgery, on both complement and granulocyte activation. Seven normal human
      volunteers were phlebotomized for ex vivo hemodialysis on two occasions each, one
      with and once without 800,000 kallikrein inhibitor units of aprotinin added to
      the circuit. Measurements were made of complement activation (radioimmunoassay
      for C3a desArg and C5a desArg), as well as granulocyte activation (flow
      cytometric measurements of reactive oxygen species (ROS) production, granulocyte
      CD11b-CD18 [MAC-1, CR3] expression, and CD62-L [L-selectin] expression).
      Statistically significant elevations in C3a desArg levels occurred by 10 minutes
      and reached a maximum of 5,367 +/- 712 ng/mL by 60 minutes after the initiation
      of ex vivo hemodialysis. Plasma C5a levels were elevated to 236 +/- 32 ng/mL at
      60 minutes compared with 45 +/- 15 ng/mL predialysis. Aprotinin was able to
      significantly inhibit dialysis-induced C3a generation (peak 2,456 +/- 572 ng/mL
      at 60 minutes) as well as C5a generation (86 +/- 23 ng/mL at 60 minutes). During
      ex vivo hemodialysis, there was also a significant increase in granulocyte ROS
      production, MAC-1 upregulation, and L-selectin downregulation. Changes in
      granulocyte activation were not affected by the administration of
      aprotinin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527185
TI  - When your surgical patient has hypertension.

PMID- 7527184
TI  - Compatibility and stability of ondansetron hydrochloride with morphine sulfate
      and with hydromorphone hydrochloride in 0.9% sodium chloride injection at 4, 22,
      and 32 degrees C.
AB  - The physical compatibility and chemical stability of ondansetron hydrochloride
      0.1 and 1 mg/mL with morphine sulfate 1 mg/mL and with hydromorphone
      hydrochloride 0.5 mg/mL in 0.9% sodium chloride injection were studied. Test
      solutions of the drugs in 0.9% sodium chloride injection were prepared in
      triplicate and stored at 4, 22, and 32 degrees C. Samples were removed
      immediately and at various time points over 31 days and stored at -70 degrees C
      until analyzed. Physical compatibility was assessed visually and by measuring
      turbidity with a color-correcting turbidimeter and particle content with a light
      obscuration particle sizer and counter. Chemical stability was determined by
      measuring the concentration of each drug in duplicate with stability-indicating
      high-performance liquid chromatography. There were no visual or subvisual changes
      in turbidity or particle content in any of the test solutions at any of the time
      points. There was little or no loss of any of the drugs. When admixed in 0.9%
      sodium chloride injection, ondansetron hydrochloride 0.1 and 1 mg/mL plus
      morphine sulfate 1 mg/mL or hydromorphone hydrochloride 0.5 mg/mL were compatible
      and stable for at least 7 days at 32 degrees C and for at least 31 days at 4 and
      22 degrees C.

PMID- 7527186
TI  - High seroprevalence of hepatitis C infection among risk groups in Egypt.
AB  - High prevalence rates of hepatitis C virus (HCV) were recently reported among
      Egyptian blood donors. To confirm these observations and estimate the magnitude
      of HCV infection in this country, we determined the prevalence of antibodies to
      HCV (anti-HCV) in samples collected in 1992 from seven different populations of
      children and adults living in Egypt. Anti-HCV was found in 12.1% of rural primary
      schoolchildren, 18.1% of residents of a rural village, 22.1% of army recruits,
      16.4% of children with hepatosplenomegaly, 54.9% of hospitalized, multitransfused
      children, 46.2% of adults on hemodialysis, and 47.2% of adults with chronic liver
      disease or hepatoma. Age-related prevalence of anti-HCV in a random sample of 270
      inhabitants of a rural village increased progressively from zero in those 5-10
      years of age to 41% in adults greater than the age of 50. Although the increased
      prevalence of anti-HCV among children and adults with parenteral exposures and
      chronic liver disease was expected, the prevalence of anti-HCV among persons
      representing the general population of Egypt was strikingly high. These data
      demonstrate the magnitude of HCV infection and its importance in chronic liver
      disease in Egypt. Future studies are needed to determine the routes of
      transmission of HCV in this country.

PMID- 7527187
TI  - Detection of Pseudomonas pseudomallei antigen in urine for the diagnosis of
      melioidosis.
AB  - An enzyme-linked immunosorbent assay using a fluorescein isothiocyanate (FITC)
      anti-FITC amplification system, has been developed to detect Pseudomonas
      pseudomallei antigen in urine. The assay was evaluated in 135 patients with acute
      melioidosis, 194 hospitalized patients with other disorders, and 40 healthy
      controls. Antigen was detected in the urine of 123 (91%) patients with
      melioidosis. Urinary antigen was found in 85 (96%) of 89 patients with septicemic
      melioidosis, all six patients with P. pseudomallei urinary tract infection, and
      32 (80%) of 40 patients with other localized infections. Antigen was not detected
      in the urine of 40 healthy individuals, but the urine of 16 (8%) of 194
      hospitalized patients with diagnoses other than melioidosis gave a positive
      result. Of the false-positive results, 13 of 16 were associated with bacteriuria
      > or = 10(4) colony-forming units/ml. At a cutoff titer of 1:10, the sensitivity
      and specificity of the test were 81% and 96%, respectively. Enzyme immunoassay
      detection of urinary antigen is a valuable and rapid laboratory test for the
      early diagnosis of acute melioidosis.

PMID- 7527188
TI  - Purification of RNA from polyacrylamide gels by ultracentrifugation.

PMID- 7527190
TI  - In situ screening assay for cell viability using a dimeric cyanine nucleic acid
      stain.
AB  - A rapid and sensitive assay is described for the determination of cell viability
      of adherent and nonadherent cells that can be performed in situ in 96-well
      microtiter plates using fluorescence plate scanners. The assay, based on dye
      exclusion, utilizes a plasma membrane-impermeable, dimeric cyanine dye (YOYO-1).
      YOYO-1 fluoresces brightly only when bound to nucleic acids. Cells are incubated
      with YOYO-1, and fluorescence is measured before and after the addition of
      detergent, which allows the dye to enter the cells. The fluorescence before
      detergent treatment originates from nonviable cells that have membrane damage and
      take up YOYO-1. The fluorescence after detergent treatment originates from all
      cells in the sample. The ratio of the two fluorescence values is used as an
      indicator of cell viability. The cell viability results of this microplate assay
      closely resemble those of dye exclusion studies by flow cytometry and are similar
      but not identical to those of the thiazolyl blue assay, which uses a metabolic
      indicator of cell death. Because the assay can be performed in situ, without
      removing the medium, disintegrated cells, cell aggregates, and cells that stick
      to culture vessel walls are all included in the measurement.

PMID- 7527189
TI  - A strategy for the mapping of N-glycans by high-performance capillary
      electrophoresis.
AB  - We have evaluated high-performance capillary electrophoresis (HPCE) with respect
      to its suitability for use in establishing a carbohydrate-mapping database that
      would enable a carbohydrate structural analysis by mere comparison of migration
      times. The suitability of HPCE for carbohydrate structural assignments was
      ascertained by validation experiments. The migration times of distinct N-glycans,
      prepared and measured on different days, were shown to be highly reproducible,
      with a coefficient of variation of usually less than 0.20%, requiring only
      femtomoles of N-glycan per injection for reliable measurements. By including
      mesityl oxide and sialic acid as internal standards and a triple-correction
      method, HPCE fulfills the analytical requirements with respect to accuracy,
      precision, reproducibility, and sensitivity. The N-glycan-mapping database was
      established using a newly developed and optimized buffer system containing 1,5
      diaminopentane as an organic modifier. Approximately 80 different sialylated N
      glycans of known structure, which have thus far been measured and characterized,
      have been entered into our Lotus 1-2-3 mapping database. The database for
      structural determinations was tested using the N-linked carbohydrates released
      from recombinant human urinary erythropoietin (baby hamster kidney) by PNGase F
      treatment and from bovine serum fetuin and alpha 1-acid glycoprotein by automated
      and manual (large-scale) hydrazinolysis, respectively. The efficiency of the
      database and of the triple-correction method was further confirmed by HPCE
      measurements performed in a different laboratory and by a different analyst who
      used the HPCE system of a different manufacturer.

PMID- 7527191
TI  - A cloning and epsilon-epitope-tagging insert for the expression of polymerase
      chain reaction-generated cDNA fragments in Escherichia coli and mammalian cells.
AB  - An intercompatible gene-tagging insert sequence was designed to conveniently
      introduce epitope-tagged polypeptides into bacteria and mammalian cells. The
      presence of rare restriction enzyme sites located between the ATG codon and the
      sequence encoding the introduced epsilon-tag creates a general cloning site which
      allows efficient cloning of virtually any desired cDNA fragment produced by the
      polymerase chain reaction (PCR). The tagging insert sequence encodes a KGF
      SYFGEDLMP peptide, derived from the last 12 amino acids of the protein kinase C
      epsilon gene, to serve as a C-terminal epitope tag of the expressed protein.
      While the insert can be readily adapted for insertion into any expression vector,
      this paper details the introduction and characterization of the epsilon-epitope
      tagging insert into the bacterial pTrcHis A (epsilon TrcHis A) vector and into
      the metallothionein promoter-driven eukaryotic (epsilon MTH) expression vector.
      The expressed epsilon-tagged proteins can be readily detected with a commercially
      available antibody specific for the epsilon-peptide. Immunoscreening of
      Escherichia coli colonies transformed with the PCR-generated cDNA inserted into
      the epsilon TrcHis A vector enables rapid, direct biochemical characterization of
      the PCR product. The biochemically characterized gene constructs from the epsilon
      TrcHis A plasmid can be inserted into the epsilon MTH vector by a single
      subcloning step using the introduced compatible cohesive ends. This epsilon
      epitope-tagging insert provides investigators with a versatile, uncomplicated,
      and reliable method of expressing an epitope-tagged PCR product in the cell type
      of interest.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527192
TI  - Immunoelectron microscopic localization of HNK-1 in the embryonic rat heart.
AB  - To confirm the role of HNK-1 in conduction tissue, the ultrastructural
      localization of monoclonal antibody HNK-1 was analyzed in developing rat hearts
      at embryonal day 14.5 by immunoelectron microscopic labeling procedures with post
      embedding immunogold staining. Tissue sections in different planes containing the
      sino-atrial (SA) node, atrio-ventricular (AV) node and His bundle were used to
      demonstrate HNK-1. Immunogold labeling was detected on the cell surfaces and in
      the extracellular matrices of cells that had features common to conduction tissue
      cells. Non-specialized contractile myocytes were not labeled by this antibody.
      Furthermore, immunogold labeling was more prominent in wide intracellular spaces
      than in narrow intercellular spaces, and rarely observed in cell-cell contact
      regions. The cell surfaces and extracellular matrices of mesenchymal cells in the
      endocardial cushion, which contacts the His bundle, were also positive,
      suggesting the involvement of tract formation to the AV node. These findings may
      indicate that HNK-1 plays an important role in cell-cell adhesion processes both
      temporally and spatially in the developing conduction tissue. It was concluded,
      therefore, that HNK-1 is a suitable marker of the embryonic heart conduction
      system and might be useful in analyzing anomalous conduction systems, as in
      congenital heart disease.

PMID- 7527194
TI  - Evidence for the expression of two distinct MHC class II DR beta like molecules
      in the sheep.
AB  - This study used monoclonal antibodies to sheep MHC class II molecules as well as
      an L cell transfectant (T8.1) which expresses DRA and DRB genes to show that two
      distinct DR beta chains are expressed in the sheep. Two anti-beta chain specific
      monoclonal antibodies VPM37 and VPM43 react with DR antigen but not DQ antigen by
      ELISA. These two antibodies do not react with the DR beta chain expressed in the
      T8.1 cell line. Two-dimensional immunoblotting shows that these antibodies
      recognize a subgroup of the spots recognized by the DR-specific monoclonal
      antibody VPM57 which does react with the T8.1 beta chain. Amino-terminal sequence
      analysis of the alpha chain associated with VPM37 beta chain shows that this
      alpha chain is homologous to the human DR alpha chain strongly indicating that
      the beta chain is DR-like. VPM37 and VPM43 are shown to be directed against
      different epitopes on sheep MHC class II molecules so it is highly unlikely that
      the data can be explained by the presence of post-translational modifications or
      the existence of a very common allele. These data provide clear evidence for the
      expression of two distinct DR beta chains in the sheep.

PMID- 7527193
TI  - Cytochemical identification of programmed cell death in the fusing fetal mouse
      palate by specific labelling of DNA fragmentation.
AB  - The process of palate fusion was examined in 13- and 14-day-old mouse fetuses by
      using in situ staining for nuclear DNA fragmentation (TUNEL method) and
      immunofluorescent staining for keratin, with special reference to the disruption
      of the midline epithelial seam. TUNEL-positive cells were found in the
      disappearing midline seam and the oral and nasal epithelial triangles at some
      late stages of palate fusion, but not in the palatal shelves prior to contact or
      in the intact midline epithelial seam. It seems that DNA fragmentation or
      apoptosis is required for the midline epithelial seam to disrupt, but may not be
      necessary for initial contact of palatal shelves or for the epithelial fusion of
      opposing palatal shelves. A similar sign of apoptotic cell death was observed in
      the disappearing epithelial seam between the fusing nasal septum and dorsal
      palate. We have demonstrated that apoptotic programmed cell death does occur at
      some stages of palate fusion, although the present results do not exclude the
      possibility of epithelial-mesenchymal transformation and the oral and nasal
      migration of midline epithelial cells.

PMID- 7527195
TI  - TaqI and MspI restriction fragment length polymorphisms at the ovine
      apolipoprotein B (APOB) locus.

PMID- 7527196
TI  - ZES-10: a new bovine MspI polymorphism detected by one primer.

PMID- 7527197
TI  - IgA deficiency associated with growth hormone deficiency in a boy with short arm
      deletion of chromosome 18 (46,XY,18p-).
AB  - The authors report a 10-year-old boy with the short arm deletion of chromosome 18
      extending to centromere with no evidence of mosaicism. Associated were growth
      hormone and IgA deficiencies. It seems to be the second example appeared in
      medical literature.

PMID- 7527199
TI  - Mechanistic studies and biological activity of bioxalomycin alpha 2, a novel
      antibiotic produced by Streptomyces viridodiastaticus subsp. "litoralis" LL
      31F508.
AB  - The bioxalomycins, a novel complex of broad-spectrum antibiotics, were isolated
      from fermentations of Streptomyces viridodiastaticus subsp. "litoralis" LL
      31F508. Bioxalomycin alpha 2, the major component of this complex, exhibited
      antibacterial activity. The MICs ranged from < or = 0.002 to 0.008 micrograms/ml
      for gram-positive organisms and from 0.50 to 4 micrograms/ml for gram-negative
      organisms. Bioxalomycin alpha 2 was found to be bactericidal and to inhibit
      bacterial DNA synthesis preferentially. Bioxalomycin alpha 2 protected mice from
      a lethal challenge with Staphylococcus aureus Smith. The 50% effective dose of
      bioxalomycin alpha 2 administered orally was 10 times greater than that when the
      drug was given subcutaneously or intravenously. These data suggest a stability or
      bioavailability problem when the compound is administered orally.

PMID- 7527198
TI  - Inhibition of human immunodeficiency virus type 1 replication by SDZ NIM 811, a
      nonimmunosuppressive cyclosporine analog.
AB  - (Me-Ile-4)cyclosporin (SDZ NIM 811) is a 4-substituted cyclosporin which is
      devoid of immunosuppressive activity but retains full capacity for binding to
      cyclophilin and exhibits potent anti-human immunodeficiency virus type 1 (HIV-1)
      activity. SDZ NIM 811 selectively inhibits HIV-1 replication in T4 lymphocyte
      cell lines, in a monocytic cell line, and in HeLa T4 cells. Furthermore, its
      antiviral activity against laboratory strains and against clinical isolates from
      geographically distinct regions in primary T4 lymphocytes and in primary
      monocytes (50% inhibitory concentration = 0.011 to 0.057 micrograms/ml) was
      demonstrated. SDZ NIM 811 does not inhibit proviral gene expression or virus
      specific enzyme functions, either free or bound to cyclophilin. The compound does
      not influence CD4 expression or inhibit fusion between virus-infected and
      uninfected cells. SDZ NIM 811 was, however, found to block formation of
      infectious particles from chronically infected cells. Oral administration to
      mice, rats, dogs, and monkeys resulted in levels in blood considerably exceeding
      the drug concentration, which completely blocked virus replication in primary
      cells. SDZ NIM 811 caused changes of toxicity parameters in rats to a smaller
      degree than cyclosporine (formerly cyclosporin A). Thus, the potent and selective
      anti-HIV-1 activity of SDZ NIM 811 and its favorable pharmacokinetic behavior
      together with its lower nephrotoxicity than that of cyclosporine make this
      compound a promising candidate for development as an anti-HIV drug.

PMID- 7527200
TI  - Isolation and characterization of a novel bacterium growing via reductive
      dehalogenation of 2-chlorophenol.
AB  - A bacterium capable of anaerobic growth via reductive dehalogenation of 2
      chlorophenol was isolated from a culture enriched from sediment taken from a
      small stream near Lansing, Mich. The organism, designated strain 2CP-1, is a gram
      negative rod ca. 3 by 0.5 micron in size and is a catalase-negative, oxidase
      negative, facultative anaerobe that forms small red colonies in anaerobic media.
      The organism grew in reduced anaerobic mineral medium supplemented with 2
      chlorophenol, acetate, and vitamins, producing phenol as a product. It did not
      grow when either 2-chlorophenol or acetate was omitted. The growth yield was
      about 3 g of protein per mol of 2-chlorophenol dechlorinated, and the doubling
      time was 3.7 days. Only the ortho position was dehalogenated, and additional
      chlorines at other positions decreased or blocked ortho dechlorination. The
      organism also grew with fumarate as its electron acceptor. Dechlorination
      activity is inducible, since cultures grown in fumarate containing medium with 2
      chlorophenol rapidly dechlorinated additional 2-chlorophenol, while cultures
      grown in the same medium without 2-chlorophenol did not. Analysis of the
      organism's 16S rRNA sequence revealed that it is a member of the delta
      proteobacteria, more closely related to the myxobacteria than to the sulfidogenic
      bacteria.

PMID- 7527201
TI  - The use of 16S rRNA-targeted oligonucleotide probes to study competition between
      ruminal fibrolytic bacteria: development of probes for Ruminococcus species and
      evidence for bacteriocin production.
AB  - A total of six oligonucleotide probes, complementary to the 16S rRNA, were
      evaluated for quantitative and determinative studies of Ruminococcus albus and
      Ruminococcus flavefaciens. On the basis of specificity studies, probes for R.
      albus (probe RAL196) and R. flavefaciens (probe RFL196) were selected to
      quantitate these species in mixed culture. In combination with a Fibrobacter
      succinogenes S85 subspecies probe (SUB1) and a domain Bacteria (formerly kingdom
      Eubacteria) probe (EUB338), they were used to quantitate these species competing
      in mixed cultures for cellobiose as the carbon source. In dicultures containing
      R. albus 8 and F. succinogenes S85, competition was not observed. However, R.
      flavefaciens FD-1 eventually outcompeted F. succinogenes S85 when cellobiose was
      the substrate. When R. albus 8 and R. flavefaciens FD-1 were grown together on
      cellobiose medium, R. albus 8 outcompeted R. flavefaciens FD-1, resulting in
      undetectable R. flavefaciens 16S rRNA only 1 to 3 h after inoculation, suggesting
      production of an antagonistic compound by R. albus 8 during rapid growth on
      soluble substrates. Further, when R. albus 8, R. flavefaciens FD-1, and F.
      succinogenes S85 were grown together in a triculture, R. flavefaciens FD-1 16S
      rRNA was detectable for only 2 h after inoculation, while R. albus 8 and F.
      succinogenes S85 showed a similar competition pattern to that of the dicultures.
      The results show that the Ruminococcus probes were effective in the measurement
      of relative populations of selected R. albus and R. flavefaciens strains during
      in vitro competition studies with F. succinogenes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7527203
TI  - Membrane-permeabilizing activities of Bacillus thuringiensis coleopteran-active
      toxin CryIIIB2 and CryIIIB2 domain I peptide.
AB  - Bacillus thuringiensis toxin CryIIIB2 exhibits activity against two
      agriculturally important pests, the Colorado potato beetle, Leptinotarsa
      decemlineata, and the Southern corn rootworm, Diabrotica undecimpunctata.
      CryIIIB2 shows significant structural similarity to Colorado potato beetle-active
      toxin CryIIIA, whose crystal structure has been determined elsewhere [J. Li, J.
      Carrol, and D. J. Ellar, Nature (London) 353:815-821, 1991]. A clone limited to
      the putative 7-alpha-helical bundle domain I peptide of CryIIIB2 was constructed
      by PCR. The truncated protein was expressed at high levels in Escherichia coli.
      Domain I peptide was isolated and compared with native CryIIIB2 toxin in
      promoting ion efflux from synthetic phospholipid vesicles and formation of ion
      channels in black lipid membranes. The results showed that CryIIIB2 domain I
      peptide is sufficient for ion channel formation and promotes ion efflux. Both
      native CryIIIB2 toxin and domain I peptide were inefficient channel-forming
      proteins that produced noisy ion channels of various conductance states. In ion
      efflux assays, native toxin promoted greater ion efflux from synthetic vesicles
      than did the truncated peptide.

PMID- 7527202
TI  - The use of 16S rRNA-targeted oligonucleotide probes to study competition between
      ruminal fibrolytic bacteria: pure-culture studies with cellulose and alkaline
      peroxide-treated wheat straw.
AB  - Specific oligonucleotide probes targeted to sites on the 16S rRNA of Ruminococcus
      albus 8, Ruminococcus flavefaciens FD-1, and Fibrobacter succinogenes S85 and a
      domain Bacteria probe were used to study bacterial interactions during the
      fermentation of cellulose and alkaline hydrogen peroxide-treated wheat straw in
      monocultures, dicultures, and tricultures. Results showed that R. albus 8
      inhibited the growth of R. flavefaciens FD-1 when grown as a diculture with
      cellulose or alkaline hydrogen peroxide-treated wheat straw as the carbon source.
      In dicultures containing R. albus 8 and F. succinogenes S85 grown on cellulose or
      alkaline hydrogen peroxide-treated wheat straw, competition was not detected. R.
      flavefaciens FD-1 outcompeted F. succinogenes S85 when cellulose was used as the
      carbon source. In tricultures with cellulose as the carbon source, R.
      flavefaciens FD-1 was inhibited, R. albus 8 appeared to dominate during the early
      phase of degradation (12 to 48 h), while F. succinogenes S85 became predominant
      during the later phase of degradation (60 to 70 h). When alkaline hydrogen
      peroxide-treated wheat straw was used as a growth substrate, F. succinogenes S85
      showed better growth than either R. albus 8 or R. flavefaciens FD-1. However, R.
      flavefaciens FD-1 was present in small numbers throughout the incubation period,
      unlike the growth patterns when cellulose was the carbon source.

PMID- 7527205
TI  - Detection of Aeromonas salmonicida, causal agent of furunculosis in salmonid
      fish, from the tank effluent of hatchery-reared Atlantic salmon smolts.
AB  - The fish pathogen, Aeromonas salmonicida, could be detected only by
      bacteriological culture from the kidney of dead or moribund fish in one tank in a
      hatchery rearing Atlantic salmon (Salmo salar L.) smolts. However, by using a DNA
      probe specific for this species, allied to a PCR assay, the pathogen could be
      detected in water, feces and effluent samples taken from this fish tank. Also,
      the presence of the pathogen was found in effluent samples from two fish tanks
      containing apparently healthy fish. Subsequently, the presence of pathogen in
      these tanks was confirmed by an increase in the daily mortality rate and by a
      plate culture from moribund fish.

PMID- 7527204
TI  - Geobacter sulfurreducens sp. nov., a hydrogen- and acetate-oxidizing
      dissimilatory metal-reducing microorganism.
AB  - A dissimilatory metal- and sulfur-reducing microorganism was isolated from
      surface sediments of a hydrocarbon-contaminated ditch in Norman, Okla. The
      isolate, which was designated strain PCA, was an obligately anaerobic,
      nonfermentative nonmotile, gram-negative rod. PCA grew in a defined medium with
      acetate as an electron donor and ferric PPi, ferric oxyhydroxide, ferric citrate,
      elemental sulfur, Co(III)-EDTA, fumarate, or malate as the sole electron
      acceptor. PCA also coupled the oxidation of hydrogen to the reduction of Fe(III)
      but did not reduce Fe(III) with sulfur, glucose, lactate, fumarate, propionate,
      butyrate, isobutyrate, isovalerate, succinate, yeast extract, phenol, benzoate,
      ethanol, propanol, or butanol as an electron donor. PCA did not reduce oxygen,
      Mn(IV), U(VI), nitrate, sulfate, sulfite, or thiosulfate with acetate as the
      electron donor. Cell suspensions of PCA exhibited dithionite-reduced minus air
      oxidized difference spectra which were characteristic of c-type cytochromes.
      Phylogenetic analysis of the 16S rRNA sequence placed PCA in the delta subgroup
      of the proteobacteria. Its closest known relative is Geobacter metallireducens.
      The ability to utilize either hydrogen or acetate as the sole electron donor for
      Fe(III) reduction makes strain PCA a unique addition to the relatively small
      group of respiratory metal-reducing microorganisms available in pure culture. A
      new species name, Geobacter sulfurreducens, is proposed.

PMID- 7527206
TI  - Inhibition of purified nitric oxide synthase from rat cerebellum and macrophage
      by L-arginine analogs.
AB  - The inhibition of nitric oxide synthase (NOS) activity by a variety of L-arginine
      related compounds has been investigated. The inhibitory properties of NG-amino-,
      NG-methyl-, NG-hydroxy-, NG-ethyl-, NG-allyl-, NG, NG-dimethyl-, NG-methoxy-L
      arginine, and several other L-arginine derivatives were compared in NOS purified
      from both macrophage and rat cerebellum. Also, these compounds were tested for
      their potential as alternate substrates by determining their ability to elicit
      NADPH consumption by NOS. NG-Methoxy-L-arginine appears to be an alternate
      substrate for NOS, whereas most other L-arginine analogs, except for the
      biosynthetic intermediate NG-hydroxy-L-arginine, do not elicit significant enzyme
      turnover.

PMID- 7527207
TI  - Coordinated expression of valine catabolic enzymes during adipogenesis: analysis
      of activity, mRNA, protein levels, and metabolic consequences.
AB  - 3T3-L1 fibroblasts have limited enzymatic capacity to oxidize valine. Enzymes
      expressed in these cells allow efficient oxidation of only the first carbon of
      this branched chain amino acid. The pathway is effectively truncated at the level
      of 3-hydroxyisobutyrate because of very low expression of two enzymes required
      for the complete pathway, 3-hydroxyisobutyrate dehydrogenase and methylmalonate
      semialdehyde dehydrogenase. These two enzymes, as well as the branched chain
      alpha-ketoacid dehydrogenase, are markedly induced upon differentiation of 3T3-L1
      fibroblasts into adipocytes. Flux through the first two decarboxylation steps of
      valine catabolism is increased dramatically after differentiation, particularly
      through the step catalyzed by methylmalonate semialdehyde dehydrogenase.
      Activation of the distal portion of the valine catabolic pathway correlates with
      significant increases in enzyme protein and mRNA levels for 3-hydroxyisobutyrate
      dehydrogenase and methylmalonate semialdehyde dehydrogenase, and this establishes
      the pathway in 3T3-L1 adipocytes for utilization of valine carbon for
      lipogenesis. The induction profiles of 3-hydroxyisobutyrate dehydrogenase and
      methylmalonate semialdehyde dehydrogenase are very similar, suggesting coordinate
      regulation of the expression of these two valine pathway-specific enzymes.
      Induction of valine catabolism in 3T3-L1 cells is solely differentiation
      dependent, suggesting regulation by the same factors that govern differentiation
      of 3T3-L1 fibroblasts into adipocytes.

PMID- 7527208
TI  - Clinicopathologic and immunohistochemical studies on lichen amyloidosis and
      macular amyloidosis.

PMID- 7527211
TI  - Noninvasive imaging of E-selectin expression by activated endothelium in urate
      crystal-induced arthritis.
AB  - OBJECTIVE: To assess the expression of the cytokine-inducible endothelial
      leukocyte adhesion molecule E-selectin during the evolution of urate crystal
      induced arthritis, using a recently described radiolabeled monoclonal antibody
      (MAb) imaging technique. METHODS: Monosodium urate (MSU) crystals and saline
      alone were injected respectively into the right (inflamed) and left (control)
      knees of 3 young pigs. Four hours later, 111In-labeled 1.2B6 F(ab')2 (anti-E
      selectin MAb) and 125I-labeled MOPC 21 F(ab')2 (control MAb) were injected
      intravenously. Uptake of 1.2B6 in inflamed and control joints was assessed by
      scintigraphy 7 and 24 hours after intraarticular injection of MSU crystals.
      Immunohistochemistry studies and radioactivity counting of tissues were performed
      postmortem to confirm the observations from scintigraphy. RESULTS: MAb 1.2B6
      F(ab')2 scintigraphic images of the knees revealed a significantly increased
      uptake in the right (inflamed) knee at 7 and 24 hours postinjection, particularly
      over the joint space. These in vivo images were consistent with E-selectin
      expression in the inflamed tissue detected by immunohistochemistry and with
      radioactivity counts postmortem. The synovial localization ratio
      (inflamed:control synovium counts) was 25.4 +/- 9.7 (mean +/- SD) for the anti-E
      selectin MAb compared with 2.5 +/- 0.9 for the control MAb (P < 0.05, by paired
      Student's t-test). CONCLUSION: E-selectin is expressed by synovial endothelium
      during the evolution of urate crystal-induced arthritis and can be detected
      noninvasively using a radiolabeled MAb. This E-selectin imaging technique has
      considerable potential for the noninvasive assessment of endothelial activation
      in arthritis and other inflammatory rheumatic diseases.

PMID- 7527209
TI  - The effects of nitric oxide inhibition on regional hemodynamics during
      hyperdynamic endotoxemia.
AB  - OBJECTIVE: To determine the effect of the inhibition of nitric oxide (NO) on
      selective organ blood flow in endotoxin-induced sepsis. DESIGN: Nonrandomized,
      controlled experiment. SETTING: Animal research facility in Brooklyn, NY.
      PARTICIPANTS: Eleven mongrel dogs. INTERVENTION: Eleven dogs were divided into
      one of two groups: a control group (n = 5) and an endotoxin-treated group (n =
      6). The animals were anesthetized, and electromagnetic and ultrasonic flow probes
      were placed on the distal aorta, right internal carotid artery, superior
      mesenteric artery, and left renal artery. Sepsis was induced with a 60-mg/kg
      intravenous injection of Escherichia coli endotoxin. When the arterial blood
      pressure decreased to less than 60 mm Hg despite adequate fluid resuscitation, NO
      synthesis was inhibited with a 25-mg/kg intravenous administration of NG
      monomethyl-L-arginine. After 15 minutes of inhibition, a 400-mg/kg intravenous
      administration of L-arginine, the substrate of NO synthase enzyme, was given.
      Physiologic measurements were continued for 15 minutes thereafter. MAIN OUTCOME
      MEASURES: Heart rate, blood pressure, central venous pressure, pulmonary artery
      pressure, pulmonary capillary wedge pressure, cardiac output, hematocrit,
      arterial and venous blood gas values, and blood flow measurements of right
      internal carotid artery, superior mesenteric artery, left renal artery, and
      distal aorta. RESULTS: Control animals did not demonstrate a significant (P >
      .05) decrease in blood flow in the internal carotid artery, superior mesenteric
      artery, and distal aorta after the administration of NG-monomethyl-L-arginine.
      The endotoxin-treated group showed a significant (P < .05) decrease in organ
      perfusion when treated with the NO synthase inhibitor, NG-monomethyl-L-arginine.
      CONCLUSIONS: Inhibition of NO production in the treatment of sepsis caused a
      significant decrease in blood flow to all vascular beds in vivo. The role, if
      any, of the inhibition of NO in the treatment of sepsis is questioned.

PMID- 7527212
TI  - Histamine release induced by pituitary adenylate cyclase activating polypeptide
      from rat peritoneal mast cells.
AB  - Pituitary adenylate cyclase activating polypeptide 38 (PACAP 38) and its
      fragments PACAP 27, PACAP 16-38, PACAP 28-38, PACAP 31-38 were compared for their
      histamine releasing effects on rat peritoneal mast cells. PACAP 38 and PACAP 16
      38 were the most active peptides, followed by PACAP 27. PACAP 38 and PACAP 16-38
      dose-dependently increased histamine release at a concentration of 1 x 10(-8)
      mol/l or higher, and these releasing activities were more than 100 times more
      potent than that of substance P. Extracellular calcium inhibited the substance P
      induced histamine release. In contrast, PACAP 38- and PACAP 27-induced histamine
      releases were hardly inhibited by extracellular calcium.

PMID- 7527210
TI  - Cat scratch disease.

PMID- 7527214
TI  - Delayed myelination in a patient with 18q- syndrome.
AB  - A Japanese boy with the typical manifestations of 18q-syndrome and delayed
      myelination on magnetic resonance imaging is described. Cytogenetic investigation
      revealed a deletion at 18q21.3. Three serial magnetic resonance images
      demonstrated that myelination in the central nervous system was delayed except
      for the corpus callosum and brainstem. This pattern of delayed myelination
      appears to be peculiar to the 18q- syndrome. Because the gene for myelin basic
      protein has been localized to the distal end of the long arm of chromosome 18, we
      speculate that the abnormal myelination in our patient was partly due to the
      failure of expression of the myelin basic protein gene.

PMID- 7527213
TI  - Congenital insensitivity to pain with anhidrosis (hereditary sensory and
      autonomic neuropathy type IV)
AB  - Congenital insensitivity to pain with anhidrosis (CIPA, hereditary sensory and
      autonomic neuropathy type IV) is an exceedingly rare disease. Only 31 cases have
      been reported. We report a 4-year-old girl with CIPA and include a complete
      review of the literature. CIPA is a severe autosomal recessive condition that
      leads to self-mutilation in the first months of life and to bone fractures,
      multiple scars, osteomyelitis, joint deformities, and limb amputation as the
      children grow older. Mental retardation is common. Death from hyperpyrexia occurs
      within the first 3 years of life in almost 20% of the patients. Ultrastructural
      and morphometric studies of the peripheral nerves demonstrate a loss of the
      unmyelinated and small myelinated fibers. The actual physiopathologic mechanism
      of this developmental disorder remains unknown.

PMID- 7527216
TI  - [Regulation of the production of IgE in man].
AB  - Allergy is associated with elevated production of allergen-specific IgE antibody.
      Naive allergen-specific B cells undergo a series of molecular interactions before
      they would produce allergen-specific IgE antibody. Besides allergen recognition,
      specific B cells have to receive signals from cell-surface proteins and cytokines
      from their various cellular partners. Activated T cells express a ligand for CD40
      that rescues germinal centre B cells from programmed cell death. Contact with
      follicular dendritic cells or other T and B cells promotes differentiation into
      plasma through engagement of two pairs of complementary cell-surface proteins,
      CD21/CD23. Among the many cytokines secreted by helper T cells, interleukin-4 is
      necessary for the class switch to IgE, and IL-13 also triggers switching to IgE.
      Then, IgE would participate to feed-back regulation of its production by acting
      at different levels. When bound to CD23, also known as Fc epsilon receptor type
      II, IgE immune complexes inhibit CD21/CD23 cell-cell interactions. When bound to
      Fc epsilon receptor type I on Langerhans' cells in the skin or mucosa, IgE
      antibody enhances allergen presentation to T cells and promotes their
      differentiation into type 2 helper T cells that secrete IL-4 but no interferon
      gamma. Local activation of mast cells or basophils, via their Fc epsilon Receptor
      type I-bound IgE, would trigger secretion of various cytokines, IL-4 in
      particular, and expression of CD21 and CD40 ligand, which altogether could
      replace contact with T cells to deliver the co-stimulatory signals for localised
      IgE production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527215
TI  - Failure to diagnose carbohydrate-deficient glycoprotein syndrome prenatally.

PMID- 7527218
TI  - Red-edge excitation fluorescence spectroscopy of proteins in reversed micelles.
AB  - The dependence of fluorescence emission maxima of L-tryptophan and single
      tryptophan-containing proteins (ribonuclease T1, melittin, and parvalbumin) on
      excitation wavelength has been studied in reversed micelle systems of sodium
      bis(2-ethyl-1-oxyl) sulfosuccinate (AOT). No effect of fluorescence maximum shift
      for different excitation wavelengths is observed for ribonuclease T1, in which a
      single tryptophan residue is located in the nonrelaxating, nonpolar protein
      interior. L-Tryptophan and the rest of the studied proteins, which contain single
      tryptophan residues exposed to the solvent, exhibit the dipolar relaxational
      processes of partly immobilized water molecules in micelles. This effect depends
      on the molar H2O/AOT ratio. Circular dichroism measurements prove that there have
      been no structural changes of the studied proteins in micellar systems. The
      results provide information about dynamic relaxational processes in proteins.

PMID- 7527217
TI  - Prediction of conformation of rat galanin in the presence and absence of water
      with the use of Monte Carlo methods and the ECEPP/3 force field.
AB  - The conformation of the 29-residue rat galanin neuropeptide was studied using the
      Monte Carlo with energy minimization (MCM) and electrostatically driven Monte
      Carlo (EDMC) methods. According to a previously elaborated procedure, the
      polypeptide chain was first treated in a united-residue approximation, in order
      to enable extensive exploration of the conformational space to be carried out
      (with the use of MCM). Then the low-energy united-residue conformations were
      converted to the all-atom representations, and EDMC simulations were carried out
      for the all-atom polypeptide chains, using the ECEPP/3 force field with hydration
      included. In order to estimate the effect of environment on galanin conformation,
      the low-energy conformations obtained as a result of these simulations were taken
      as starting structures for further EDMC runs that did not include hydration. The
      lowest-energy conformation obtained in aqueous solution calculations had a
      nonhelical N-terminal part packed against the nonpolar face of a residual helix
      that extended from Pro13 toward the C-terminus. One next lowest-energy structure
      was a nearly-all-helical conformation, but with a markedly higher energy. In
      contrast, all of the low-energy conformations in the absence of water were all
      helical differing only by the extent to which the helix was kinked around Pro13.
      These results are in qualitative agreement with the available NMR and CD data of
      galanin in aqueous and nonaqueous solvents.

PMID- 7527220
TI  - Endodermal sinus tumor: immunophenotypic expression of a carcinoma.
AB  - A series of five endodermal sinus tumors was studied for their cytoskeletal and
      other phenotypic markers. They included 2 ovarian, 2 testicular, and 1 inguinal
      tumors. The cytoskeletal expression was also studied by gel electrophoresis and
      immunoblotting. Every tumor was diffusely and strongly immunostained for
      cytokeratin. By SDS-PAGE and immunoblotting, cytokeratins 8 & 18 were detected.
      Vimentin was focally coexpressed in 4 cases. The stroma was diffusely
      immunostained for vimentin. None of them expressed desmin, neurofilament, or
      glial filament protein. Desmoplakin was expressed only in one ovarian tumor.
      Alpha-fetoprotein and S-100 protein were also diffusely positive among the
      neoplastic cells; intracytoplasmic globules were especially strongly
      immunostained. These findings suggest that endodermal sinus tumors represent a
      group of pure malignant epithelial neoplasms, and may be regarded as primitive
      carcinomas.

PMID- 7527219
TI  - Immunoreactivity between a monoclonal lupus autoantibody and the
      arginine/aspartic acid repeats within the U1-snRNP 70K autoantigen is
      conformationally restricted.
AB  - Immunoreactivity of the arginine/aspartic acid (RD) repeats of the 70K protein of
      U1 small nuclear ribonucleoprotein (snRNP) was determined to be conformationally
      dependent. The monoclonal autoantibody 2.73, isolated from a lupus-prone MRL/n
      mouse model, is reactive with the RD repeat regions of U1 snRNP 70K protein.
      Immunochemical analysis of the antigenic determinants with use of chemically
      synthesized peptides characterized the 2.73 epitope as the RD repeat [Pelsue, S.,
      et al. (1993) Autoimmunity, 15, 231-236] Analysis by circular dichroism (CD) and
      nuclear magnetic resonance spectroscopy indicates conformational preferences in
      the immunoreactive peptides. Computer analyses of CD spectra obtained on the RD
      containing peptides predict beta-turns and beta-sheet to be the preferred
      conformations of the RD repeats. This structure was also predicted by the Chou
      Fasman algorithm. The RD repeat is believed to be a conserved structural motif;
      however, the biological function is still unclear. Immunological and biochemical
      analysis of autoimmune antibodies and their respective antigenic determinants has
      helped to characterize the possible mechanisms that lead to autoimmune diseases.
      This is the first report of a conformationally dependent, linear epitope of an
      autoantibody.

PMID- 7527221
TI  - Vascular biology: relevance of nitric oxide in vascular and nonvascular tissue
      with normal and decreased renal function.
AB  - Nitric oxide has been recognized as an important paracrine or autocrine system
      during the past decade. The generalized importance of this rather simple molecule
      has been demonstrated in of a variety of neural, epithelial, vascular and immune
      systems. The degree to which alterations in nitric oxide metabolism contribute to
      the physiologic and pathophysiologic status of patients with end-stage renal
      disease remains to be fully defined in both experimental animals and in humans
      afflicted with renal disease.

PMID- 7527222
TI  - The pseudo epidermis. An in vitro model for dermatological investigations.

PMID- 7527223
TI  - Using dyes and filters in a fluorescent imaging system.
AB  - The FluorImager fluorescence imaging system uses monochromatic 488-nm laser light
      to excite fluorochromes. It contains a built-in 515-nm long-pass filter that
      rejects excitation laser light, but allows emission light with wavelengths longer
      than 515 nm to pass through. A fluorochrome appropriate for use in the system is
      excitable by 488-nm light and emits at least some of its fluorescence at
      wavelengths longer than 515 nm. Two types of optical filters, long-pass and band
      pass, are used in the system. Long-pass filters reject shorter wavelengths and
      transmit longer wavelengths. The number in the filter name denotes the cutoff
      wavelength (midpoint of the transition between rejected and transmitted light)
      for the filter. Band-pass filters transmit a band of wavelengths and reject both
      shorter and longer wavelengths. The numbers in the filter name denote the center
      wavelength of the passed band and the width of the band at half maximum
      transmission. Generally, when scanning for a single fluorochrome, only the built
      in 515-nm long-pass filter is needed. An interchangeable filter can be added to
      decrease the contribution from a broad-spectrum background signal and to
      attenuate strong fluorochrome signals.

PMID- 7527224
TI  - Amplification-based diagnostics target TB.

PMID- 7527225
TI  - Fourier-transform infrared assay of bile salt-stimulated lipase activity in
      reversed micelles.
AB  - A Fourier-transform infrared (FT-IR) spectroscopic method has been developed for
      assaying the bile salt-stimulated human milk lipase (BSSL, EC3.1) catalyzed
      hydrolysis of triolein in AOT reversed micelles in iso-octane. At 37 degrees C in
      50 mmol dm-3 AOT the molar absorbtivities for the carbonyl stretching frequencies
      for triolein (at 1751 cm-1) and oleic acid (at 1714 cm-1) were 1646 dm3 mol-1 cm
      1 and 743 dm3 mol-1 cm-1, respectively. The rate was linearly dependent upon the
      concentration of enzyme in the water pool up to 10 mg cm-3 and maximum activity
      was observed at a ratio (w0) of [H2O]:[AOT] = 16.7. Using these conditions, and
      in the presence of 10 mmol dm-3 sodium taurocholate (TC), the derived Michaelis
      Menten parameters Vmax and Km were 57.5 mumol min-1 mg-1 and 5.53 mmol dm-3,
      respectively. These results are compared with those obtained in an oil-in-water
      microemulsion system and are discussed in terms of the relative partitioning of
      the enzyme and the substrate in the aqueous and oil phases and the interfacial
      concentration of the substrate in the two systems.

PMID- 7527226
TI  - Liquid-liquid extraction of a recombinant protein with reverse micelles.
AB  - Recombinant cytochrome b5 was extracted into the reversed micelle phase of an
      anionic surfactant (AOT) in octane and back-extracted to a final aqueous phase.
      The extraction of the protein was controlled by an electrostatic mechanism, since
      it was dependent on the global charge of the protein. This was directly
      demonstrated by experiments with native and mutant cytochromes obtained by site
      directed mutagenesis. The back-extraction of cytochrome b5 to a fresh aqueous
      phase was decreased by factors that reduced the size of the water pool of the
      organic phase, such as high salt concentrations (1-2 mol dm-3 NaCl) and low
      temperatures (4 degrees C), probably because of an increase in a favourable
      interaction of this protein with the surfactant at closer distances.

PMID- 7527227
TI  - Sympathetic innervation of the eustachian tube in rats.
AB  - The glyoxylic catecholaminergic histofluorescence method was employed on the
      mucosa of the rat's eustachian tube (ET) in order to study the sympathetic
      innervation present. One percent neutral red was used as counterstain. Many
      noradrenergic fibers were demonstrable around blood vessels, glands and submucosa
      of the ET, but not in the epithelium. In a group of rats following neurectomy,
      the superior cervical ganglia (SCG) were removed unilaterally or bilaterally.
      Changes in sympathetic innervation of the ET were examined 14 days after SCG
      ganglionectomy. In those animals after unilateral SCG ganglionectomy, no
      noradrenergic histofluorescence was found in the ipsilateral ET, although some
      scant fluorescence could be detected in the tube's nasopharyngeal (NP) orifice.
      However, no noradrenergic histofluorescence could be observed in animals
      bilateral SCG ganglionectomies. Our results indicate that sympathetic innervation
      of the ET in the rat originates in the SCG, with some cross-innervation of
      sympathetic fibers occurring in the tube's NP orifice.

PMID- 7527228
TI  - Ruthenium red antagonism of capsaicin-induced vascular changes in the rat nasal
      mucosa.
AB  - Mechanisms of capsaicin-induced vascular changes were examined in the nasal
      mucosa of anesthetized adult rats. Intra-arterial infusions of capsaicin at doses
      of 20-100 pmol/min into the external carotid artery resulted in a dose-dependent
      increase in nasal blood flow as assessed by laser-Doppler flowmetry. Intra
      arterial infusion of ruthenium red (RR, 2.5-10 mumol) prior to the administration
      of capsaicin significantly inhibited the capsaicin-evoked response. The technique
      of vascular labelling was used to examine nasal mucosal vascular permeability.
      Intravenous administration of colloidal silver solution prior to capsaicin
      infusion resulted in accumulation of colloid in the walls of small blood vessels,
      indicative of enhanced vascular permeability. Vascular labelling was largely
      abolished after RR pretreatment. These findings suggest that neuropeptides
      released from trigeminal sensory nerve endings play a significant role in the
      local vascular and inflammatory reactions of the nasal mucosa. The experimental
      approach utilized in this study provides a promising model for defining the roles
      of capsaicin-sensitive afferent nerves in the mechanisms of allergic and/or
      inflammatory diseases affecting the nasal mucosa.

PMID- 7527230
TI  - Molecular properties of a superfamily of plasma-membrane cation channels.
AB  - The principal subunits of a large superfamily of plasma-membrane cation channels
      are functionally autonomous in ion conductance and in gating by membrane
      potential and intracellular ligands. Recent work has located the structural
      elements responsible for the ion conductance and gating of these channels. These
      studies reveal strong functional analogies among the different ion channels and
      suggest that the striking differences in their properties arise as variations on
      a common structural and functional theme.

PMID- 7527231
TI  - Surgical interventions in ischemic ventricular tachyarrhythmias--endocardial
      resection or implanted cardioverter/defibrillator.
AB  - The surgical therapy of ventricular tachyarrhythmias (VTA) in ischemic heart
      disease is attracting attention, since current medical therapies are showing
      limited long-term efficacy. The curative concept of electrophysiologically guided
      endocardial resection (ER) and palliation with the implantable
      cardioverter/defibrillator (ICD) are compared retrospectively. From 1980-1992,
      121 patients (55 +/- 9 years, 108 males, 13 females) underwent ER and 203
      patients (59 +/- 9 years, 195 males, 8 females) received an ICD for ischemic VTA.
      Concomitant coronary revascularization was performed in 38/121 patients with ER
      (31%) and in 62/203 patients (31%) with ICD. Perioperative mortality was 8%
      (10/121 patients) for ER and 5% (10/203 patients) for ICD (P = n.s.). Hundred
      eleven patients with ER (mean follow-up 41 +/- 37 months) and 193 with ICD (mean
      follow-up 22 +/- 20 months) were available for survival analysis: freedom from
      sudden death was comparable for the two groups at 1 year (99% for ICD, and 94%
      for ER) and at 5 years (90% for ICD and 90% for ER) (P = n.s.). Freedom from
      cardiac death also showed no differences between the groups at 1 year (94% for
      ICD, and 84% for ER) and at 5 years (74% for ICD and 74% for ER) (P = n.s.). Left
      ventricular function, indicated by left ventricular ejection fraction, was
      comparable (34 +/- 9% in ER, 30 +/- 11% with ICD) (P = n.s.) in the two groups.
      The linearized incidence of DC-shocks was 10.3/year in ICD patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7527232
TI  - The management of tracheobronchial obstruction: a review of endoscopic
      techniques.
AB  - Tracheobronchial obstruction is a distressing cause of morbidity and mortality in
      patients with benign and malignant disease. Resection offers curative treatment
      for a few, but for the majority of patients who are too frail for surgery, and
      for those benign and malignant cases where the disease is too extensive for
      resection, there is a need for an effective method of palliation. We
      retrospectively reviewed the results of a 9-year experience in 86 patients with
      major airways obstruction (51 malignant and 35 benign) treated on one or more
      occasions using various endoscopic techniques. Nineteen patients presented as an
      emergency. Thirty-nine had received other forms of treatment beforehand including
      external radiotherapy and laser resection (Nd:YAG). Treatment undertaken in our
      institution was: diathermy resection (36 patients), gold grain implantation (16
      patients), bougienage (9 patients), cryotherapy (2 patients), Montgomery T-tube
      and T-Y stent (28 patients) and varied endotracheal and endobronchial stents (40
      patients). Twenty-two patients were treated with more than one modality at the
      first treatment session. Twenty-one patients required revision of their
      endobronchial stents or T-tubes because of displacement or partial occlusion by
      mucous accretions. There were no intraoperative deaths or complications and the
      average length of stay was 5 days (range: 2 to 14 days). Eighty-three patients
      reported immediate symptomatic relief. Objective improvement in lung function
      tests was demonstrated in patients whose condition was less acute and
      preoperative measurements could be made. In the diathermy resection group there
      was an average improvement in forced expiratory volume in 1 s (FEV1) of 53.1% and
      in the forced vital capacity (FVC) of 20.6%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527233
TI  - Kinetic analysis of engineered antibody-antigen interactions.
AB  - Molecular engineering of antibodies has made it possible to produce specific
      domains of the antibody molecule and combine them with other protein domains to
      achieve new properties. Using site directed mutagenesis, amino acid residues can
      be exchanged within the binding site; and, by analysis of crystal structures, the
      positions of these amino acids can be determined in three dimensions at atomic
      resolution. In addition, gene libraries and phage selection technology can be
      used to generate new antibody fragments directly from a gene pool. Both
      mutagenesis and selection from libraries offer opportunities to identify antibody
      derived molecules with altered and useful antigen recognition properties. The
      detailed analysis of both kinetic and equilibrium binding affinity are therefore
      essential to understand the activity of the molecules resulting from antibody
      engineering and to guide the progress of their further design. This paper reviews
      recently evolving techniques for the binding analysis of antibodies, their
      functional domains and antibody chimerae.

PMID- 7527229
TI  - Serum and urine inorganic fluoride levels following prolonged low-dose
      sevoflurane anesthesia combined with epidural block.
AB  - STUDY OBJECTIVES: To determine whether serum and urine inorganic fluoride levels
      with prolonged (more than 7 hours) low-dose (0.8 to 2.0 vol %) sevoflurane
      anesthesia plus epidural anesthesia were increased as compared with isoflurane
      anesthesia plus epidural anesthesia. To measure the urine tubular enzymes N
      acetyl-beta-glucosaminidase (NAG), alpha 1-microglobulin (alpha 1-M), and beta 2
      microglobulin (beta 2-M) for renal tubular injury in both groups. DESIGN:
      Randomized, prospective study. SETTING: University hospital. PATIENTS: 15 ASA
      physical status I and II adults (7 males, 8 females) who were scheduled for
      prolonged laparotomy (lasting 9.5 to 10.2 hours) with general anesthesia.
      MEASUREMENTS AND MAIN RESULTS: Epidural anesthesia was administered before
      induction of general anesthesia. General anesthesia was induced with thiamylal
      administered intravenously (IV), and the trachea was intubated following
      administration of vecuronium IV. It was maintained with either sevoflurane or
      isoflurane in nitrous oxide and oxygen. Standard monitoring was used in all
      patients. Serum and urine inorganic fluoride and urine tubular enzymes were
      measured periodically. Serum inorganic fluoride was 54 mumol/L at 4.3 minimum
      alveolar concentration (MAC) hours of sevoflurane; the peak level for isoflurane
      was 8 mumol/L at the same MAC hours. Sevoflurane also increased urine inorganic
      fluoride excretion to 96 mumol/hr 8 hours. NAG excretion started to increase
      after inhalation of either sevoflurane or isoflurane. alpha 1-M and beta 2-M
      excretion increased markedly postoperatively. Even though fluoride levels and
      tubular enzymes were high, there was no evidence of postoperative renal
      dysfunction. CONCLUSIONS: There was no increase in urinary enzymes, which are
      indicators of tubular injury, specific to sevoflurane. There was no postoperative
      renal dysfunction, as indicated by unchanged serum creatinine and blood urea
      nitrogen levels.

PMID- 7527234
TI  - Binding of native and [homoserine lactone-52]-52,53-seco-bovine basic pancreatic
      trypsin inhibitor (Kunitz inhibitor) to porcine pancreatic beta-kallikrein-B and
      bovine alpha-chymotrypsin: thermodynamic study.
AB  - Values of the association equilibrium constant (Ka) for the binding of the native
      and of the cyanogen bromide-cleaved bovine basic pancreatic trypsin inhibitor
      (native BPTI and [Hse lactone-52]-52,53-seco-BPTI, respectively) to neuraminidase
      treated porcine pancreatic beta-kallikrein-B (kallikrein) and bovine alpha
      chymotrypsin (chymotrypsin) have been determined between pH 4.0 and 9.0, at 20.0
      degrees C. Over the whole pH range explored, native BPTI and [Hse lactone-52]
      52,53-seco-BPTI show the same affinity for kallikrein. On the other hand, the
      affinity of [Hse lactone-52]-52,53-seco-BPTI for chymotrypsin is higher, around
      neutrality, than that found for native BPTI by about one order of magnitude,
      converging in the acidic pH limb. The simplest mechanism accounting for the
      observed data implies that, on lowering the pH from 9.0 to 4.0, (i) the decrease
      in affinity for the binding of native BPTI to kallikrein and chymotrypsin, as
      well as for the association of [Hse lactone-52]-52,53-seco-BPTI to kallikrein,
      reflects the acidic pK shift, upon inhibitor association, of a single ionizing
      group; and (ii) the decrease of Ka values for [Hse lactone-52]-52,53-seco-BPTI
      binding to chymotrypsin appears to be modulated by the acidic pK shift, upon
      inhibitor association, of two non-equivalent proton-binding residues. On the
      basis of the stereochemistry of the serine proteinase/inhibitor contact
      region(s), these data indicate that long-range structural changes in [Hse lactone
      52]-52,53-seco-BPTI are energetically linked to the chymotrypsin:inhibitor
      complex formation. This observation represents an important aspect for the
      mechanism of molecular recognition and regulation in BPTI.

PMID- 7527236
TI  - Host cell components affect the sensitivity of HIV type 1 to complement-mediated
      virolysis.
AB  - An infection-competent, full-length HIV-1 clone (pNL4-3) was expressed in seven
      human cell lines and in peripheral blood mononuclear cells in order to assess the
      contribution of host cell components toward interaction of free virus with the
      complement system. HIV-1 expressed in the H9 cell line, which is frequently used
      for in vitro infection, was relatively susceptible to complement-mediated
      virolysis in the presence of both HIV antibody-positive patient serum and an anti
      V3 monoclonal antibody. Expression of complement receptors 1, 2, and 3,
      complement control proteins membrane inhibitor of reactive lysis (MIRL, CD59) and
      decay-accelerating factor (DAF, CD55), and HLA-DR was assessed on host cells.
      There was an inverse relationship between the sensitivity of virus to complement
      and the amount of expression of MIRL and DAF on cells. HIV derived from the JY
      cell line and the mutant JY33 cell line, which is deficient in expression of
      phosphatidylinositol (PI)-linked proteins including MIRL and DAF, were also
      evaluated for complement-mediated virolysis. Virus expressed in the mutant cell
      line was more sensitive to antibody-independent as well as antibody-dependent
      complement-mediated virolysis than virus expressed in the wild-type cells. Direct
      demonstration of the presence of MIRL and DAF on the viral surface was obtained
      by showing that anti-MIRL or anti-DAF antibody induced complement-mediated
      virolysis. These experiments show that the host cell type can substantially
      influence the susceptibility of HIV to complement-mediated virolysis and suggest
      that PI-linked complement control proteins play an important role in this
      resistance.

PMID- 7527237
TI  - [Self-expandable metal prostheses. A new alternative palliative therapy of
      malignant stenotic lesions of the esophagus].
AB  - The treatment of malignant esophageal stenoses is a serious problem which may
      have a surgical solution at diagnosis in only a selected number of cases.
      Chemotherapy and radiotherapy are the main palliative treatments; surgery has a
      high morbidity and mortality rate. The insertion of esophageal prostheses could
      be an alternative palliative treatment. From January 1991 to November 1993, 41
      autoexpandable metallic prostheses (12 Wallstent type, 19 Strecker type and 1
      Rosch-Uchida type) have been implanted in 30 patients with esophageal cancer one
      with lung cancer and two with radiation induced esophagitis. Technical success
      resulted in 28 patients; an initial failure requiring a new prosthesis insertion
      occurred in 5 patients. Technical aspects and results are analyzed.

PMID- 7527239
TI  - Expanded programme on immunization. Certification of poliomyelitis eradication
      the Americas, 1994.

PMID- 7527240
TI  - Evidence for a selective inhibitory effect of thrombin on megakaryocyte
      progenitor growth mediated by the thrombin receptor.
AB  - An efficient method for the culture of human megakaryocyte precursors in serum
      free medium has been developed facilitating study of the effect of regulators of
      megakaryocyte growth and maturation without interference by serum-derived
      factors. We have investigated how megakaryocytes and their precursors respond to
      the procoagulant enzyme, thrombin. In addition to its already documented agonist
      effect on mature megakaryocytes, thrombin was found to have a marked inhibitory
      effect on the growth of megakaryocyte colonies from CD34+ bone marrow cells
      stimulated by IL3. This inhibitory effect, not previously reported, was selective
      for megakaryocytic cells. The growth of granulomonocytic and erythroid colonies
      was not affected. A monoclonal antibody which neutralized the effect of exogenous
      transforming growth factor beta (TGF beta) was unable to fully neutralize the
      inhibitory effect of thrombin. With the use of a synthetic peptide, corresponding
      to the tethered thrombin receptor ligand, and of a recombinant inactive form of
      thrombin, we provide direct evidence that both the inhibitory effect of thrombin
      on megakaryocyte proliferation and its agonist effect on mature megakaryocytes
      are mediated by a receptor analogous to the recently cloned platelet thrombin
      receptor.

PMID- 7527238
TI  - [Perforation from gastrojejunostomy: 2 cases].

PMID- 7527235
TI  - Dying well: symptom control within hospice care.

PMID- 7527241
TI  - Human melanoma cell lines differ in their capacity to release ADP and aggregate
      platelets.
AB  - In this study we have investigated, using three different human melanoma cell
      lines (M1Do., M3Da., M4Be.). the varying capacity of melanoma cells to induce
      platelet aggregation in the presence or absence of inhibitors of ADP or thrombin.
      The expression levels of different integrins (alpha v, beta 3, alpha v beta 3,
      alpha IIb, alpha v beta 3) were evaluated by immunoprecipitation, binding and
      flow cytometry studies. The level of ADP in supernatants of melanoma cells were
      quantified by ADP bioassay and HPLC. Platelets were irreversibly aggregated by
      M3Da, as shown by electron microscopy, in contrast to M1Do, which induced a slow
      reversible aggregation. M4Be. did not induce platelet aggregation. In both cases,
      with M3Da. or M1Do., apyrase but not PPACK inhibited platelet induced
      aggregation. An anti-alpha v beta 3 monoclonal antibody (LYP18) or polyclonal
      antibody inhibited platelet aggregation. A similar number of LYP18 molecules
      bound to the surface of M1Do., M3Da. and M4Be. cell lines. Biological HPLC assays
      of ADP present in the supernatant of tumour cell lines showed the highest
      concentration of ADP to be secreted by M3Da., followed by M1Do., and none
      detected for M4Be. These results show that differences in in vitro aggregating
      potential of the three human melanoma cell lines are not related to low integrin
      expression levels but to their ability to generate ADP. Generation of ADP by
      human melanoma cells may act as important modulator of melanoma-platelet
      interactions.

PMID- 7527243
TI  - Transient loss of proteins carrying Kell and Lutheran red cell antigens during
      consecutive relapses of autoimmune thrombocytopenia.
AB  - A patient is described in whom two consecutive relapses of autoimmune
      thrombocytopenic purpura (AITP) were associated with loss of red cell antigens of
      the Kell and Lutheran blood group systems respectively. During the second relapse
      the glycoprotein CD44 and to a lesser extent the LW antigen were also depressed.
      Both relapses were associated with concomitant production of IgG antibody
      recognizing high-frequency determinants on the corresponding antigen-carrying
      protein. Blocking of antigen sites by these antibodies was not the cause of
      reduced antigen expression, because immunoblotting studies showed absence of Kell
      protein during the first relapse, and Lutheran protein during the second. On both
      occasions the red cell changes reverted to normal with disappearance of the
      antibody as the AITP entered remission. There was no evidence of clonal
      lymphocyte expansion as demonstrated using immunoglobulin JH and T cell receptor
      beta chain probes.

PMID- 7527242
TI  - Nondeletional type of hereditary persistence of fetal haemoglobin: molecular
      characterization of three unrelated Thai HPFH.
AB  - The beta-globin gene clusters of three unrelated Thai families with a
      nondeletional type of hereditary persistence of fetal haemoglobin (HPFH) were
      studied using polymerase chain reaction-related techniques. All appeared to have
      normal nucleotide sequences from the Cap site to position -400 of both the G
      gamma- and A gamma-globin genes. Two individuals suspected of having a beta
      thalassaemia gene linked to the high HbF condition also had a normal beta-globin
      gene sequence, spanning from position -108 from the Cap site to the
      polyadenylation site. Deletion of four nucleotides, AGCA, at positions -225 to 
      222 of one A gamma-globin allele was detected in one subject and was confirmed by
      dot-blot hybridization. Restriction fragment length polymorphisms in the beta
      globin gene cluster showed that the 5' haplotype (-+-++) and the presence (+) of
      an Xmm 1 polymorphic site at -158 of the G gamma-globin gene are associated with
      the high F phenotype in these families. Direct sequencing of the 5'
      hypersensitive-2 (5' HS-2) site of the locus control region (LCR) showed that
      this Xmn 1 (+) site is also linked to a specific rearrangement of TA repeats
      (TA)9CACATATACG(TA)10, in HS-2 segment.

PMID- 7527245
TI  - Multiple aberrant splicing of the p53 transcript without genomic mutations around
      exon-intron junctions in a case of chronic myelogenous leukaemia in blast crisis:
      a possible novel mechanism of p53 inactivation.
AB  - We found three truncated p53 transcripts in a patient with chronic myelogenous
      leukaemia in blast crisis carrying chromosome 17 abnormalities. Sequencing of
      these transcripts revealed complete absence of the entire exons 7, 8 and 9 in
      one, exons 8 and 9 in another, and exon 10 in the other. Sequencing analysis of
      genomic DNA, however, revealed no mutation in exons 6-10 and their flanking
      introns. These results suggest that the aberrant p53 transcripts in this case
      might not result from splicing mutations but from an unknown affected splicing
      process.

PMID- 7527246
TI  - Permissive effect of cyclic AMP and cycloheximide for induction by sodium
      butyrate of the glycoprotein hormone alpha-subunit gene in choriocarcinoma cells.
AB  - Expression of the chorionic gonadotropin alpha-subunit (alpha CG) gene is
      regulated differently in human tumor cell lines derived from trophoblastic and
      nontrophoblastic tissues. This is based, at least in part, on the observations
      that production of alpha CG is increased by cAMP but not by sodium butyrate in
      choriocarcinoma cells (JEG-3), whereas production of alpha CG is increased by
      butyrate but not by cAMP in cervical carcinoma cells (HeLa). Data presented
      herein confirm that the steady-state levels of alpha CG mRNA are increased
      approximately 10-fold by cAMP in JEG-3 cells, but additionally demonstrate that
      these levels can be further increased (to 25-fold) by sodium butyrate in
      conjunction with the cyclic nucleotide. Similar effects were achieved with the
      phorbol ester 12-0-tetradecanoylphorbol-13-acetate, which also acted
      synergistically with cAMP to increase alpha CG mRNA levels (24-fold). Butyrate
      and 12-0-tetradecanoylphorbol-13-acetate had little or no effect when added alone
      (1.5-fold and 2.5-fold, respectively) or in combination with one another (3.8
      fold). Induction of the alpha CG gene by cAMP was independent of protein
      synthesis, as mRNA levels were comparable when JEG-3 cells were treated with cAMP
      in the absence and presence of cycloheximide (CHX). Unexpectedly, alpha CG mRNA
      levels were also elevated 8- to 10-fold in response to a combination of butyrate
      and CHX, but CHX alone or in combination with 12-0-tetradecanoylphorbol-13
      acetate had no effect. Gel mobility shift assays demonstrated changes in the
      pattern of proteins binding to a cAMP response element and to a trophoblast
      specific element with nuclear extracts from cells treated with CHX but not with
      cAMP or sodium butyrate. Together, these results suggest that induction patterns
      of the alpha CG gene by butyrate and cAMP in trophoblast- and nontrophoblast
      derived tumor cell lines are less distinct than suggested previously and indicate
      that CHX, which is permissive for induction by butyrate, causes a significant
      shift in electrophoretic mobility of trans-acting factors involved in alpha CG
      gene expression.

PMID- 7527247
TI  - Report on the clinical effects of inadvertent radiation underdosage in 1045
      patients.
AB  - Between Autumn 1982 and Winter 1991, 1045 patients received lower doses of
      radiation than were prescribed for the treatment of their cancers because of a
      miscalculation of radiation doses. This occurred as a result of the introduction
      of a new technique of treatment planning. An error in the application of the
      planning system lead to an underdosage of radiation of between 5 and 35%. In
      patients who received radiation alone for radical treatment a dose reduction of
      20% or more resulted in a lower than expected local control rate. The effects
      were less marked in patients who were treated by combinations of surgery and
      radiation and in those with a very high rate of distant metastases. In 1991, a
      new computer planning system was installed and a discrepancy was discovered
      between the new plans and those from the previous system. Further investigation
      revealed that the original planning system already contained within it a
      correction factor for the tumour to skin distance and that systematically
      reapplying this correction had resulted in underdoses of radiation being
      delivered to patients for nearly 10 years. During the 9-year period of this dose
      miscalculation only 6% of patients treated in the department were treated with
      the isocentric technique; for many of those it formed only a part of their
      treatment.

PMID- 7527244
TI  - Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte
      colony stimulating factor (rhG-CSF): an analysis of factors correlating with the
      tempo of engraftment after transplantation.
AB  - Factors affecting mobilization and engraftment were analysed in 54 patients
      undergoing transplant using autologous PBSCs mobilized with high-dose recombinant
      granulocyte stimulating factor (rhG-CSF). Patients received 5-7 d of rhG-CSF, 16
      micrograms/kg/d, administered subcutaneously. PBSCs were harvested by
      leukapheresis using automated continuous-flow blood cell separators beginning on
      day 4 of rhG-CSF, processing 10 litres of whole blood, for 2-6 consecutive days.
      Transplants were performed for the following diseases: breast cancer (n = 22),
      non-Hodgkin's lymphoma (n = 18), multiple myeloma (n = 7) and other (n = 7).
      Engraftment was rapid with patients reaching a neutrophil count of 1 x 10(9)/l a
      median of 12 d (range 9-22) after transplant. Platelets > 20 x 10(9)/l
      independent of transfusion support were achieved a median of day 10 (range 7-60)
      after infusion. Multiple factors potentially influencing engraftment were
      examined using a Cox regression model. The number of CD34+ cells per kg was
      highly correlated with the time to achievement of granulocyte and platelet
      recovery (P < 0.012, 0.0001). The use of a post-infusion growth factor and a
      radiation preparative regimen was important for neutrophil recovery, and a
      diagnosis of breast cancer was important for platelet recovery. In an analysis by
      linear regression of the logarithm of CD34+ cells collected, lower age, marrow
      without disease, no prior radiation, and lower number of prior chemotherapy
      regimens, were important factors influencing larger numbers of CD34+ cells in
      collections.

PMID- 7527249
TI  - A patient with spontaneous regression of urothelial malignancy.
AB  - A 65-year-old male presented with prostatic transitional cell carcinoma,
      metastatic to lungs and lymph nodes. He was treated with palliative radiotherapy
      to the primary site. No other anticancer treatment was given. Almost 2 years
      later he is well with no signs or symptoms of progressive disease and the lung
      metastases seen on his chest radiograph have completely disappeared.

PMID- 7527248
TI  - Prophylactic supraclavicular fossa radiotherapy in early breast cancer: is it
      worthwhile?
AB  - A total of 291 consecutive patients with early breast cancer who did not receive
      any supraclavicular prophylactic irradiation of the ipsilateral fossa have been
      followed for a minimum of 5 years. Isolated relapse in that site occurred in 4.5%
      of patients and was controlled by radical radiotherapy with a post-relapse 5-year
      survival of 33%. Relapse with co-existing distant metastases occurred in a
      further 7% and no patient survived to 3 years. Supraclavicular fossa irradiation
      contributes to morbidity, does not improve survival and should be abandoned in
      favour of delayed treatment for proven recurrence.

PMID- 7527251
TI  - Protein synthesis in vivo in rats fed on lipid-rich liquid diets.
AB  - Changes in tissue composition and protein synthesis ratio were studied in the
      major tissues of the body in young rats fed on lipid-rich, isonitrogenous
      purified liquid diets, a convenient method for inducing voluntary overfeeding
      under controlled nutritional conditions. Overfed rats showed faster growth
      induced by the energy excess. Analysis of tissue composition (protein, DNA and
      RNA contents) revealed that growth was due mainly to tissue hyperplasia in which
      protein and DNA contents increased in parallel. Fractional protein synthesis
      ratio measured in vivo by the flooding-dose method of phenylalanine showed a
      marked increase in all tissues. This change could be attributed to an increase in
      the ribosomal activity for protein synthesis in most tissues. Therefore, our
      results indicate that addition of a supplementary energy source (as lipids) to a
      well-balanced diet improves growth and protein synthesis in growing rats.

PMID- 7527250
TI  - Controlled release of macromolecules from a degradable polyanhydride matrix.
AB  - Polymeric matrices that slowly release macromolecules may be useful for the
      controlled delivery of proteins or polymer-drug conjugates for targeted drug
      delivery. Solid particles of fluorescein and fluorescently-labeled, size
      fractionated dextran (4000-150,000 number average molecular weight) were
      dispersed in degradable polyanhydride matrices composed of a 1:1 copolymer of
      fatty acid dimers and sebacic acid. The release of macromolecules from the
      polymer matrix into buffered saline was measured; changes in the polymer during
      immersion were monitored by infrared spectroscopy, differential scanning
      calorimetry, and scanning electron microscopy. Although significant hydrolysis of
      the polymer occurred within the first day, the matrices remained intact and water
      soluble tracers were slowly released for several days. During polymer hydrolysis
      and erosion, micron-sized pores developed throughout the 2 mm thick polymer
      matrix, permitting water penetration into the matrix and tracer diffusion out of
      the matrix. The rate of tracer release from the matrix depended on tracer
      particle size; rates of fluorescein isothiocyanate dextran release were
      controlled by adjusting the size of particles dispersed in the matrix.

PMID- 7527253
TI  - Invasive sinonasal disease due to Scopulariopsis candida: case report and review
      of scopulariopsosis.
AB  - Sinonasal infection with fungi of the order Mucorales--termed mucormycosis or
      zygomycosis--is sometimes seen in immunosuppressed patients, including those with
      diabetic ketoacidosis and malignancy. We describe a case of invasive sinonasal
      infection with Scopulariopsis candida (not among the Mucorales organisms) in a 12
      year-old girl who was being treated for non-Hodgkin's lymphoma. Only a few cases
      of invasive infection with Scopulariopsis species have been reported previously;
      five of six of these cases were associated with persistent or fatal disease. Our
      patient survived without undergoing radical surgical debridement and was treated
      with granulocyte colony-stimulating factor, amphotericin B, and itraconazole;
      chemotherapy was stopped. In vitro susceptibility testing of our patient's
      Scopulariopsis isolate showed that it was resistant to amphotericin B and that it
      was relatively susceptible to itraconazole and miconazole. The case described
      herein demonstrates the expanding spectrum of fungal organisms that may cause
      invasive sinonasal infection in immunocompromised hosts and the need for reliable
      antifungal susceptibility testing.

PMID- 7527252
TI  - [Solitary metastasis of prostate cancer in the tibia].
AB  - We report about a patient with a solitary tibial metastasis of a prostatic
      carcinoma. Metastases to the peripheral skeleton are relatively rare with a
      frequency of only 1-2% and are mainly found in cases of general spread of the
      disease. Complaints due to peripheral solitary metastases often cause
      misinterpretations. Bone scintigraphy is the primary method in the diagnosis of
      skeletal metastases, and is sometimes supported by specific radiographs. MRI
      yields excellent images of the extension of the tumor. It is therefore of high
      diagnostic value in the preoperative definition of the metastatic spread in bone
      and neighbouring soft tissue structures.

PMID- 7527255
TI  - Positive predictive value of Rochalimaea henselae antibodies in the diagnosis of
      cat-scratch disease.

PMID- 7527254
TI  - High predictive value of the acid-fast smear for Mycobacterium tuberculosis
      despite the high prevalence of Mycobacterium avium complex in respiratory
      specimens.
AB  - The value of the smear for acid-fast bacilli in predicting pulmonary tuberculosis
      is unclear in a setting where there is a high prevalence of Mycobacterium avium
      complex in respiratory specimens. To evaluate the impact of a high prevalence of
      M. avium complex on the predictive value of the acid-fast bacilli smear for
      tuberculosis, we reviewed findings on smears and results of cultures over a 3
      year period at a hospital where M. avium complex is the predominant mycobacterial
      isolate. In this setting, the predictive value of the acid-fast bacilli smear for
      Mycobacterium tuberculosis was 92% for expectorated sputum specimens, 71% for
      induced sputum specimens, and 71% for bronchoalveolar lavage specimens. When
      multiple specimens collected from the same patient were excluded from the data
      base, the predictive values were 87%, 70%, and 71%, respectively. Smears of
      sputum samples were positive at the same rate for patients with tuberculosis who
      had AIDS and for patients with tuberculosis who did not have AIDS.

PMID- 7527256
TI  - Use of enhanced chemiluminescence to quantify protein adsorption to calcium
      phosphate materials and microcarrier beads.
AB  - The adsorption of serum proteins to calcium phosphate bone substitute materials,
      positively-charged dextrose and negatively-charged polystyrene microcarrier beads
      was compared by SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis). Protein adsorption to hydroxyapatite (HA)-based materials was
      influenced by chemical composition. Surface charge sign, distribution and/or
      functional group affected protein adsorption to microcarrier beads. Enhanced
      chemiluminescence was used to quantify adsorption of fibronectin and vitronectin
      following Western blotting, and to monitor the kinetics of adsorption of these
      two proteins to HA and Biosilon. Relative to total protein, fluctuating levels of
      fibronectin were detected on both materials. In contrast, vitronectin adsorption
      increased over the course of the incubation period with maximal relative
      adsorption detected after 30 min on Biosilon and 60 min on HA.

PMID- 7527257
TI  - The effect of tripotassium dicitrato bismuthate on the rat stomach.
AB  - BACKGROUND: Bismuth has been used as symptomatic treatment of dyspepsia for many
      years. It promotes healing of peptic ulcers and reduces their recurrence. The
      beneficial effect of bismuth on duodenal ulcer disease is thought to be due to an
      effect on Helicobacter pylori, although it has a rather weak bactericidal effect
      on H. pylori in vitro. Eradication of H. pylori in duodenal ulcer patients by a
      combination of bismuth, tetracycline and metronidazole has been reported to
      increase the density of somatostatin-producing D cells in the antrum. A reduced D
      cell density in the antral mucosa of duodenal ulcer patients could explain their
      exaggerated gastrin release. AIMS/METHODS: To test the possibility that bismuth
      could affect the neuroendocrine cells independently of the presence of H. pylori
      or not, we gave rats a diluted tripotassium dicitrato bismuthate solution by
      gastric gavage for 14 days. RESULTS: Tripotassium dicitrato bismuthate treatment
      did not affect maximal pentagastrin-stimulated acid secretion or histamine
      release in isolated rat stomachs or the density of argyrophil cells in the
      oxyntic and antral mucosa. However, it significantly reduced the duodenal
      concentration of gastrin and calcitonin gene-related peptide, and the density of
      G cells in the antrum and duodenum. CONCLUSION: The effect of tripotassium
      dicitrato bismuthate on the G cell may be of significance for its beneficial
      effect on duodenal ulcer disease.

PMID- 7527258
TI  - [Color Doppler ultrasound determination of the differential structure of breast
      tumors].
AB  - Eighty-seven women with mammographically suspicious breast lesions were
      investigated prior to surgery. 32 breast carcinomas and 55 benign lesions were
      evaluated for the resistance index, the pulsatility index, the flow velocity and
      the acceleration index. Our study showed the resistance index with a threshold
      value of 0.70 to be best suited to differentiate benign tumors from malignant
      ones. In this series, the sensitivity of color Doppler ultrasonography for the
      detection of breast carcinomas was 84%, and the specificity 80%. The positive
      predictive value was 71% and the negative predictive value 90%. Color Doppler
      scanning offers one possible method for further investigation of patients with
      mammographic abnormalities and can help to reduce the number of unnecessary
      breast biopsies.

PMID- 7527259
TI  - New treatments for benign prostatic hypertrophy.

PMID- 7527262
TI  - [The effect of calcium current blockers on potential-dependent potassium currents
      of cultured frog developing skeletal muscle cells].

PMID- 7527261
TI  - Extending the B7 (CD80) gene family.
AB  - B7-1 and B7-2 are members of the immunoglobulin superfamily (IgSF) and important
      regulators of T cell-mediated immune responses. Despite sharing only limited
      sequence identity, B7-1 and B7-2 bind common receptors, CD28 and CTLA-4, on T
      cells and have similar functional properties. We have found that the
      extracellular V (ariable)-like domains of B7-1 and B7-2 share significant
      sequence similarities with 3 major histocompatibility complex (MHC)-encoded
      members of the IgSF: butyrophilin, myelin/oligodendrocyte glycoprotein, and the
      chicken MHC molecule, B-G. This raises the question whether there is an
      evolutionary link between the MHC, which encodes molecules regulating the antigen
      specificity of T lymphocyte responses, and B7 molecules, which co-stimulate these
      responses in antigen-nonspecific fashion.

PMID- 7527260
TI  - Mouse liver NAD(P)H:quinone acceptor oxidoreductase: protein sequence analysis by
      tandem mass spectrometry, cDNA cloning, expression in Escherichia coli, and
      enzyme activity analysis.
AB  - The amino acid sequence of mouse liver NAD(P)H:quinone acceptor oxidoreductase
      (EC 1.6.99.2) has been determined by tandem mass spectrometry and deduced from
      the nucleotide sequence of the cDNA encoding for the enzyme. The electrospray
      mass spectral analyses revealed, as previously reported (Prochaska HJ, Talalay P,
      1986, J Biol Chem 261:1372-1378), that the 2 forms--the hydrophilic and
      hydrophobic forms--of the mouse liver quinone reductase have the same molecular
      weight. No amino acid sequence differences were found by tandem mass spectral
      analyses of tryptic peptides of the 2 forms. Moreover, the amino-termini of the
      mouse enzymes are acetylated as determined by tandem mass spectrometry. Further,
      only 1 cDNA species encoding for the quinone reductase was found. These results
      suggest that the 2 forms of the mouse quinone reductase have the same primary
      sequences, and that any difference between the 2 forms may be attributed to a
      labile posttranslational modification. Analysis of the mouse quinone reductase
      cDNA revealed that the enzyme is 273 amino acids long and has a sequence
      homologous to those of rat and human quinone reductases. In this study, the mouse
      quinone reductase cDNA was also ligated into a prokaryotic expression plasmid
      pKK233.2, and the constructed plasmid was used to transform Escherichia coli
      strain JM109. The E. coli-expressed mouse quinone reductase was purified and
      characterized. Although mouse quinone reductase has an amino acid sequence
      similar to those of the rat and human enzymes, the mouse enzyme has a higher
      NAD(P)H-menadione reductase activity and is less sensitive to flavones and
      dicoumarol, 2 known inhibitors of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527263
TI  - mRNA levels and methylation patterns of the 2-5A synthetase gene in control and
      Alzheimer's disease (AD) fibroblasts.
AB  - We have examined the mRNA levels and methylation patterns of the interferon
      inducible 2',5'-oligoadenylate (2-5A) synthetase gene in skin fibroblasts derived
      from AD and age/sex-matched control subjects. Northern or slot hybridization
      analysis of total RNA showed a 63% and 46% decrease in the steady state level of
      2-5A synthetase mRNA in AD cells as compared to controls, following a 24 h and 48
      h treatment with IFN-beta ser. The 2-5A synthetase gene as studied by Southern
      analysis using the methylation-sensitive restriction enzymes HpaII and Msp I was
      found to be hypomethylated in AD cells. No difference in methylation patterns of
      the actin gene existed between control and AD fibroblasts.

PMID- 7527264
TI  - Organization of a Sulfolobus solfataricus gene cluster homologous to the
      Escherichia coli str operon.
AB  - The Sulfolobus solfataricus S12, S7 and S10 ribosomal proteins and the elongation
      factor 1 alpha genes are organized in a sequence analogous to that in the
      Escherichia coli str operon. Northern analysis showed that the S12 gene belongs
      to a transcript different from that corresponding to the other three genes.
      Compared to the Sulfolobus acidocaldarius S12 and to the Methanococcus vannielii
      S7 proteins, the S. solfataricus S12 and S7 proteins were 33 and 47 amino acids
      longer respectively. These differences were eliminated if the 5' flanking regions
      of the S. acidocaldarius S12 and the M. vannielii S7 genes were translated from a
      different start codon. Despite the structural similarities between the archaeal
      and the bacterial str operons the S. solfataricus ribosomal proteins S12, S7 and
      S10 are more similar to the eukaryotic counterparts.

PMID- 7527265
TI  - Early lymphocyte activation events are inhibited by antiproliferative synthetic
      peptide 2438, a fragment of human interferon alpha-2, and immunosuppressant
      cyclosporine A.
AB  - A synthetic peptide (designated 2438) corresponding to the human interferon alpha
      2 amino acid sequence 124-138 inhibits proliferation of T-lymphocytes in vitro.
      Time-course experiments suggest that peptide 2438 affects early stages of
      lymphocyte activation. Molecular mechanisms of peptide 2438 action were studied.
      By western-blotting with monoclonal antibodies against phosphotyrosine peptide
      2438 was shown to decrease the phosphotyrosine content of an endogenous protein
      substrate (M.M. = 36 kDa) in human lymphocytes activated with concanavalin A
      (ConA). Similar effect on tyrosine-specific phosphorylation in mitogen-stimulated
      lymphocytes was observed with the native interferon or Cyclosporine A (CsA).
      Calcium fluxes induced by ConA in human lymphocytes were measured using a
      fluorescent calcium chelator Fura-2. In contrast to CsA, peptide 2438 did not
      affect the ConA-induced calcium influx in lymphocytes.

PMID- 7527266
TI  - Neuropsychological outcome and quantitative image analysis of acute haemorrhage
      in traumatic brain injury: preliminary findings.
AB  - The effect on neuropsychological outcome of the number of acute haemorrhages,
      lesion volume, and lesion location in traumatic brain injury (TBI) was evaluated.
      Haemorrhagic lesion volume was associated with severity of injury. However, the
      number of petechial haemorrhages was not reliably associated with any of the
      clinical outcome measures. Likewise, despite the use of detailed morphometric
      methods to quantify volume, the acute lesion size did not significantly relate to
      neuropsychological sequelae. Furthermore, brain quadrant localization methods did
      not enhance outcome prediction. These results are discussed in the context of
      acute lesion analysis contrasted with chronic TBI-induced neuropathological
      changes associated with neuropsychological outcome.

PMID- 7527268
TI  - Re-examining the concept of severity in traumatic brain injury.
AB  - This paper re-examines the theoretical concept of severe brain injury focusing on
      the duration of coma as a precise indicator of the clinical profile. A
      retrospective hospital chart study of 361 traumatic brain-injured patients was
      undertaken to determine the homogeneity of the subsample of the severely brain
      injured (defined as 2 or more days of coma) with respect to the probability of
      four types of impairment: ataxia, contractures, paralysis and speech impairment.
      The current concept of severity assumes homogeneity among the 'severely brain
      injured'. However, our results indicate significant differences in impairment
      within this population. The authors feel strongly that future studies must
      describe coma duration in finer gradations, and test for homogeneity within
      samples before inferences are made. Improvements in life-sustaining technologies
      have resulted in longer coma durations. The need to use coma days as an indicator
      of impairment rather than a broad category of severity is emphasized.

PMID- 7527269
TI  - A novel mutation (M1V) in the translation initiation codon of the cystic fibrosis
      transmembrane conductance regulator gene, in three CF chromosomes of Italian
      origin.

PMID- 7527267
TI  - Severe closed-head injury in childhood: linguistic outcomes into adulthood.
AB  - The language functioning of a group of adults who had sustained a severe closed
      head injury in childhood was evaluated. The subjects were administered a battery
      of language assessments including measures of syntax, semantics and pragmatics,
      as well as a measure of metalinguistic ability. Performance of the experimental
      group was compared with that of a control group matched for age, sex and
      educational level. Results indicated that all areas of language competence
      assessed (syntax, semantics, pragmatics) appeared to be compromised by the
      childhood closed-head injury.

PMID- 7527270
TI  - Expression and down-regulation by retinoic acid of IGF binding protein-2 and -4
      in medium from human neuroblastoma cells.
AB  - Insulin-like growth factors (IGFs) regulate the autocrine/paracrine growth of
      neuroblastomas. The IGFs bind to specific binding proteins (IGFBPs) which
      modulate their biological activity. We investigated, by Western ligand blotting
      (WLB), the presence of IGFBPs and their possible modulation by retinoic acid
      (RA), IGF-I, IGF-II and truncated Des(1-3)IGF-I in conditioned medium (CM) of the
      human neuroblastoma SK-N-BE(2) cell line. We demonstrated the presence of two
      IGFBPs, with MW 37 kDa and 25 kDa. Following immunoprecipitation, they turned out
      to be IGFBP-2 and -4, respectively. The RA-induced differentiation in SK-N-BE(2)
      cells was accompanied by a marked reduction of the intensity of both IGFBP bands
      after 48 h (32% and 24% of control, respectively) and 72 h (2% and 0% of control,
      respectively) incubation. The addition of exogenous IGFs, which did not induce
      cell differentiation, did not change the IGFBP pattern significantly, except for
      the truncated form of IGF-I, which induced a marked decrease in both the 37 kDa
      and 25 kDa bands after 72 h incubation (45% and 18% of control, respectively).
      These findings suggest that IGFBPs have a role in RA-induced differentiation in
      human neuroblastoma cells.

PMID- 7527272
TI  - A mixed message for cystic fibrosis gene therapy.

PMID- 7527271
TI  - Administration of an adenovirus containing the human CFTR cDNA to the respiratory
      tract of individuals with cystic fibrosis.
AB  - We have administered a recombinant adenovirus vector (AdCFTR) containing the
      normal human CFTR cDNA to the nasal and bronchial epithelium of four individuals
      with cystic fibrosis (CF). We show that this vector can express the CFTR cDNA in
      the CF respiratory epithelium in vivo. With doses up to 2 x 10(9) pfu, there was
      no recombination/complementation or shedding of the vector or rise of
      neutralizing antibody titres. At 2 x 10(9) pfu, a transient systemic and
      pulmonary syndrome was observed, possibly mediated by interleukin-6. Follow-up at
      6-12 months demonstrated no long term adverse effects. Thus, it is feasible to
      use an adenovirus vector to transfer and express the CFTR cDNA in the respiratory
      epithelium of individuals with CF. Correction of the CF phenotype of the airway
      epithelium might be achieved with this strategy.

PMID- 7527273
TI  - A style-specific hydroxyproline-rich glycoprotein with properties of both
      extensins and arabinogalactan proteins.
AB  - A basic, hydroxyproline-rich glycoprotein (molecular mass 120 kDa) has been
      purified from the styles of Nicotiana alata. An antibody, specific for the
      protein backbone (molecular mass 78 kDa) of the glycoprotein, was used to
      demonstrate that the glycoprotein is a soluble, style-specific component and that
      related molecules are present in the styles of other solanaceous species. Linkage
      analysis of the carbohydrate portion of the glycoprotein, together with antibody
      binding studies, indicates that the glycoprotein contains both extensin-like and
      arabinogalactan-protein (AGP)-like side chains. Furthermore, the AGP-like side
      chains contain a style-specific epitope that is also present on AGPs from N.
      alata styles and glycoconjugates from the styles of other members of the
      Solanaceae. The abundance of this 120 kDa glycoprotein, its location in the
      extracellular matrix of the transmitting tract and its conservation in several
      species within the Solanaceae suggests a role in pistil function.

PMID- 7527274
TI  - Legionnaires' disease surveillance: England and Wales, 1993.
AB  - One hundred and twenty-nine cases of legionnaires' disease were reported in
      England and Wales in 1993. Twenty-two of the cases died. Sixty-six cases (51%)
      were associated with travel (in the United Kingdom or abroad), six were
      associated with a stay in hospital, and the remaining 57 were thought to have
      acquired infection in the community. Two community and two hospital outbreaks
      were recognised in England and Wales and four outbreaks were detected in
      travellers from the United Kingdom to Spain, Greece, and the United States. One
      hundred and six cases (82%) were not known to have been associated with
      outbreaks, and 51 (40%) of these were not associated with travel or hospitals.

PMID- 7527275
TI  - Investigating a single case of Legionnaires' disease: guidance for consultants in
      communicable disease control.
AB  - When a single case of legionnaires' disease is reported, it should be
      investigated to check whether or not it is linked to other cases or part of an
      outbreak. The investigation includes confirmation of the diagnosis, tracing the
      patient's movements during the incubation period, and reporting the case to the
      National Surveillance Scheme for Legionnaires' Disease at the PHLS Communicable
      Disease Surveillance Centre. If no common factors are identified between the
      cases and other cases reported previously, no further action is usually required,
      unless it is suspected that the infection was acquired in hospital. In these
      circumstances, the individual case and the hospital's water maintenance programme
      should be reviewed, and a search made for associated cases, because hospital
      patients are particularly susceptible to infection. Further steps may be
      necessary if the link with the hospital is confirmed.

PMID- 7527276
TI  - Survey of human immunodeficiency virus infection among pregnant women in England
      and Wales: 1990-93.
AB  - We report on the first four years (1990-93) of a survey within the national HIV
      prevalence monitoring programme. The survey's objective is to monitor the
      prevalence of infection with the human immunodeficiency virus (HIV) in pregnant
      women in London and elsewhere in England. The survey--based in forty centres that
      offer antenatal care in London, Greater Manchester, West Yorkshire, and adjacent
      non-metropolitan areas--uses repeated cross sectional serosurveillance for anti
      HIV-1 and 2 and the unlinked anonymous test method on blood left over from
      specimens collected for antenatal screening for immunity to rubella. The
      seroprevalence of HIV-1 ranged from 0.007% (1 in 14,530) in non-metropolitan
      areas, to 0.011% (1 in 8790) in metropolitan areas outside London, and 0.23% (1
      in 440) in London. Evidence of HIV-2 infection was found in only four specimens,
      in London (1 in 50,300). The seroprevalence of HIV-1 in London varied more than
      tenfold between centres, from 0.03% (1 in 3190) to 0.51% (1 in 200). The highest
      prevalence of infection was in London in women aged between 20 and 30 (0.30%; 1
      in 335). The seroprevalence in London centres rose from 0.18% in 1990 (1 in 560)
      to 0.26% in 1993 (1 in 390) and the rise was significant in all age groups. If
      voluntary confidential HIV testing (with counselling) among pregnant women in
      England were to be promoted, its cost effectiveness would be greater if focused
      on particular centres that provide antenatal care in London.

PMID- 7527281
TI  - A case of diphtheria from Pakistan.

PMID- 7527277
TI  - Survey of local policies for prevention of congenital toxoplasmosis.
AB  - District policies for the primary and secondary prevention of congenital
      toxoplasmosis in England, Wales, Jersey, and the Isle of Man were surveyed in
      1992. Consultants in communicable disease control were asked to describe past,
      present, and proposed prenatal screening programmes and current health education
      policies. One hundred and eighty-seven out of 196 districts responded to a postal
      questionnaire. One district had a prenatal screening programme for toxoplasmosis
      and five were discussing possible programmes. Over half (55%) had never had a
      programme or considered introducing one and 68 (36%) districts had decided
      against screening. Fifty-four per cent of districts had health education policies
      on toxoplasmosis, and most of these provided leaflets in antenatal clinics. A
      sample of districts that in 1992 were considering or had not ruled out screening
      was followed up in February 1994. None had implemented a screening policy. All
      but one district, therefore, are following the recommendation by a working group
      of the Royal College of Obstetricians and Gynaecologists that prenatal screening
      for toxoplasmosis should not be introduced in the United Kingdom. The value of
      current health education policies in the primary prevention of congenital
      toxoplasmosis needs to be assessed.

PMID- 7527282
TI  - Legionnaires' disease in Birmingham.

PMID- 7527283
TI  - Isolation of non-LTR retrotransposon reverse transcriptase-like sequences from
      phlebotomine sandflies.
AB  - Reverse transcriptase-like sequences (RTs) with amino acid motifs characteristic
      of non-LTR retrotransposons have been isolated from several medically important
      phlebotomine sandfly species. These sequences were amplified using the polymerase
      chain reaction (PCR) with primers based on conserved amino acid motifs present in
      previously described insect RTs. A further set of RTs were amplified using
      primers based on the conserved regions identified in phlebotomine RTs. The
      average similarity of the phlebotomine RTs to the Drosophila I, F and R1Dm
      elements was 28-29% between the closest primers used. Phlebotomine RTs were 31
      62% similar to each other, the most dissimilar sequences coming from the same
      species. Several amino acid residues were invariant in the ten phlebotomine RTs,
      including motif Q(F/Y)GF, conserved in other non-LTR retrotransposons, but not in
      retrovirus or LTR retrotransposon RTs. The remarkable conservation of this
      distinctive domain of non-LTR retrotransposon RTs suggests it has a vital and
      possibly unique role in the mode of reverse transcription of this class of
      transposon.

PMID- 7527285
TI  - Organotypic growth and differentiation of human mammary gland in sponge-gel
      matrix supported histoculture.
AB  - Blocks of breast tissue obtained during radical mastectomies from 23 patients
      with mammary gland carcinomas were used for cultivation in native-state, gel
      supported histocultures. We show that the human mammary gland can be successfully
      maintained in this system so that normal epithelial breast structures proliferate
      and undergo differentiation for several weeks and a well-developed system of
      ducts and lobules is formed. Using antibodies to individual keratins 17 and 8 we
      have shown for the first time that ducts and alveoles developing in vitro undergo
      differentiation into the lining epithelium and myoepithelium in the same way as
      mammary gland epithelium in vivo. Growth of epithelial structures in vitro is
      also accompanied by the development of continuous basal membrane.

PMID- 7527284
TI  - Properties of the fluorescent sodium indicator SBFI in rat and rabbit cardiac
      myocytes.

PMID- 7527286
TI  - Differentiation of immortalized epithelial cells derived from cystic fibrosis
      airway submucosal glands.
AB  - Cystic fibrosis (CF) involves abnormalities in mucus production and secretion of
      the airway. Studies of the regulation of airway mucin production and secretion
      has been difficult due to the lack of in vitro models of the airway epithelial
      cells which express functional differentiation. Because the majority of the mucin
      in the airway is apparently produced by the submucosal glands, we have focused
      our attention on the development of cell culture models of human airway
      submucosal glands. This report describes the propagation of CF airway submucosal
      gland epithelial cells which continue to express mucin production. The CF
      bronchus was obtained from a 31-yr-old patient who received a double lung
      transplant. The glands were dissected out and primary cultures prepared by the
      explant/outgrowth procedure. The cells were immortalized by infection with Ad12
      SV40 hybrid virus. The cultures are maintained in serum-free keratinocyte basal
      medium supplemented with insulin (5 micrograms/ml), hydrocortisone (0.5
      microgram/ml), epidermal growth factor (10 ng/ml), bovine pituitary extract (25
      micrograms/ml), and antibiotics. Cultures were passaged using 0.125% trypsin in
      Ca+2 and Mg(+2)-free Hanks', balanced salt solution. Polymerase chain reaction
      (PCR) analysis demonstrated that the cells were homozygous for the delta F508
      mutation. Morphologic observations showed that the cells were epithelial and were
      interconnected by sparsely distributed desmosomes. Their cytoplasm contained
      secretory-type structures including abundant Golgi, rough endoplasmic reticulum,
      and secretory vesicles. Immunofluorescent studies determined that all cells were
      positive for cytokeratins, mucin glycoconjugates, and cystic fibrosis
      transmembrane conductance regulator. The cultures secreted substantial amounts of
      mucin glycoproteins and expressed the MUC-2 mucin gene.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7527287
TI  - Use of ionic detergents for enterovirus recovery from waste water.
AB  - Virus recovery from poliovirus-seeded waste water was attempted after treatment
      of the samples with ionic detergents in the presence of acoustic energy. Viral
      titers strongly fluctuated depending upon concentration and chemical structure of
      the detergent as well as upon the dissolved organic content of the aqueous
      samples. Supplementation of the cellular monolayers with an additional amount of
      cell culture medium or with a nonionic detergent in a subcytotoxic concentration
      48 h after inoculation partly induced cytopathic effects in silent dilution
      steps. Since, in the presence of the same detergent, viral recovery rates varied
      with the type of waste water, titer-conditioning activity of detergents was
      suggested to depend upon their effective critical micellization concentration.
      Especially for virus recovery from concentrated waste water, treatment with
      strongly disruptive detergents such as sodium dodecylsulfate revealed to be much
      more efficient than with the less hydrophilic sodium N-laurylsarcosine, sodium
      glycodeoxycholate or lauryldimethylamine-oxide, whereas the opposite seemed to be
      the case if virus recovery from filtrate samples were to be optimized. The
      mechanisms by which viral particles become infectious for the cell appear to be
      triggered by general principles of equilibrium thermodynamics, which means that
      interactions between viral surface proteins and cellular receptor molecules seem
      to reflect the tendency of these reagents to assume the energetically most
      favored orientation.

PMID- 7527288
TI  - AMPA/Zn(2+)-induced neurotoxicity in rat primary cortical cultures: involvement
      of L-type calcium channels.
AB  - Zn2+ is believed to be an endogenous modulator of glutamatergic excitation. It
      has been shown to attenuate NMDA receptor-mediated excitation and to increase
      AMPA-induced excitatory transmission. The dual activity of Zn2+ on ionotropic
      excitatory neurotransmission suggests that Zn2+ plays a role in the modulation of
      excitatory neurodegenerative events. Stimulation of rat primary cortical cultures
      with the combination of 50 microM AMPA and 300 microM Zn2+ for 30 min induced
      approximately 50% cell death compared with only approximately 20% cell death
      induced by AMPA alone. The degree of neurotoxicity 48 h after the incubation was
      reproducible and was attenuated by CNQX, EDTA, EGTA, diltiazem and DHP-type Ca2+
      channel blockers but not by MK-801. These findings suggest that an initial
      depolarization induced by AMPA and a subsequent influx of Ca2+ and Zn2+ ions
      through voltage-operated L-type Ca2+ channels are crucial events which finally
      lead to neuronal death. Racemic nimodipine and its (+)- and (-)-enantiomers had
      remarkable in vitro neuroprotective efficacies, the IC50 values being 4 nM for
      the racemate, 11 nM for the (+)- and 1 nM for the (-)-enantiomer. This suggests a
      possible therapeutic role for Ca2+ channel blockers in neurodegenerative diseases
      which are characterized by a disturbance of cellular Ca2+ homeostasis.

PMID- 7527289
TI  - Late-onset selective neuronal damage in the rat spinal cord induced by continuous
      intrathecal administration of AMPA.
AB  - Neurotoxicity mediated by 1-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      was investigated by infusing this agent continuously for 7 days intrathecally to
      adult rats using a mini-osmotic pump. Behavioral changes were apparent only after
      the second postoperative day, when the rats displayed hindlimb palsy or
      incontinence of urine. The behavioral deficits became progressively severe and
      the rats usually displayed both hindlimb paraplegia and incontinence of urine by
      the 7th postoperative day. These progressive behavioral deficits were induced in
      a dose-dependent manner in the rats that received AMPA at a dose of > 100 pmol/h
      (100 microM at 1 microliter/h, 17 nmol in total dose). The severity of behavioral
      deficits was in parallel with that of neuropathological changes in the
      lumbosacral cords. In spinal segments rostrally adjacent to those with severe
      pathological changes, only the neurons in the dorsal horns (Rexed's laminae II
      IV) were destroyed with intense gliosis. These changes were not induced by
      infusing AMPA for 1 day. The concomitant administration of 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), an antagonist for non-N-methyl-D-aspartate
      (NMDA) receptors, with AMPA, but not that of 2-amino-5-phosphonovalerate (APV),
      an antagonist for NMDA receptor, prevented induction of the behavioral and
      neuropathological changes. The findings of the present study suggest that this
      late-onset, selective neurotoxicity is mediated by AMPA-type glutamate receptors.

PMID- 7527291
TI  - The pancreatitis-associated protein (PAP). A new candidate for neonatal screening
      of cystic fibrosis.
AB  - Neonatal screening of cystic fibrosis (CF) is presently based on immunoreactive
      trypsin (IRT) assay in blood spots, whose low specificity is a matter of concern.
      Because the pancreatitis-associated protein (PAP) proved to be a better serum
      marker of pancreatic alteration than exocrine enzymes, it might be an interesting
      alternative for CF screening. We report here a preliminary evaluation of the PAP
      test, conducted in retrospect on blood spots from groups of neonates already
      screened for CF with the IRT. Neonates with elevated IRT were submitted to
      subsequent analysis of the Cystic Fibrosis Transmembrane Conductance Regulator
      (CFTR) gene. Neonates with normal IRT (n = 990) or high IRT but normal genotype
      (n = 28) had normal PAP. Elevated PAP was observed in all CF neonates (n = 11).
      False-positives for the PAP test were found only among neonates with high IRT and
      heterozygotes for a mutation in the CFTR gene (6 out of 17 cases). That group
      represents less than 0.2% of newborns. These results therefore suggest that PAP
      discriminates CF neonates with a significantly better specificity than IRT.

PMID- 7527290
TI  - alpha 4 beta 2 subunit combination specific pharmacology of neuronal nicotinic
      acetylcholine receptors in N1E-115 neuroblastoma cells.
AB  - Pharmacological characteristics of native neuronal nicotinic acetylcholine
      receptor-mediated ion currents in mouse N1E-115 neuroblastoma cells have been
      investigated by superfusion of voltage clamped cells with known concentrations of
      the agonists acetylcholine, nicotine and cytisine, and the antagonists alpha
      bungarotoxin and neuronal bungarotoxin. The sensitivity of the nicotinic
      acetylcholine receptor for agonists followed the agonist potency rank-order:
      nicotine approximately acetylcholine >> cytisine. The EC50 values of
      acetylcholine and nicotine are 78 microM and 76 microM, respectively. Equal
      concentrations of acetylcholine and nicotine induce inward currents with
      approximately the same peak amplitude whereas cytisine induces much smaller
      inward currents. Acetylcholine-induced currents are unaffected by high
      concentrations of alpha-bungarotoxin. Conversely, at 10 and 90 nM neuronal
      bungarotoxin reduces the amplitude of the 1 mM acetylcholine-induced inward
      current to 47% and 11% of control values, respectively. Both the agonist potency
      rank-order and the differential sensitivity to snake toxins of nicotinic
      receptors in N1E-115 cells are consistent with the known pharmacological profile
      of alpha 4 beta 2 nicotinic receptors expressed in Xenopus oocytes and distinct
      from those of all other nicotinic acetylcholine receptors of known functional
      subunit compositions. All data indicate that the native nicotinic acetylcholine
      receptor in N1E-115 cells is an assembly of alpha 4 and beta 2 subunits, the
      putative major subtype of nicotinic acetylcholine receptor in the brain.

PMID- 7527292
TI  - Risperidone treatment for severe negative symptoms.

PMID- 7527294
TI  - Sensitive nested reverse transcription polymerase chain reaction detection of
      circulating prostatic tumor cells: comparison of prostate-specific membrane
      antigen and prostate-specific antigen-based assays.
AB  - A highly sensitive nested reverse transcriptase-PCR assay, with primers derived
      from the prostate-specific antigen (PSA) and prostate-specific membrane antigen
      (PSM) cDNA sequences, has been used to detect occult hematogenous micrometastatic
      prostate cells. In 77 patients with prostate cancer, PSM and PSA primers detected
      circulating prostate cells in 48 (62.3%) and 7 (9.1%) patients, respectively. In
      treated stage D disease patients, PSM primers detected cells in 16 of 24 patients
      (66.7%), while PSA primers detected cells in 6 of 24 (25%). In post-radical
      prostectomy patients with negative serum PSA values, PSM primers detected
      metastases in 21 of 31 patients (67.7%), whereas PSA primers detected cells in
      only 1 of 33 (3.0%), indicating that micrometastatic spread may be a relatively
      early event in prostate cancer. The analysis of 40 individuals without known
      prostate cancer provides evidence that this assay is highly specific and suggests
      that PSM expression may predict the development of cancer in patients without
      clinically apparent prostate cancer. Using PSM primers, we detected
      micrometastases in 4 of 40 controls, 2 of whom had known benign prostatic
      hyperplasia and were later found to have previously undetected prostate cancer.
      The clinical significance of detection of hematogenous micrometastic prostate
      cells using PSM primers and potential applications of this molecular assay, as
      well as the assay for PSA, merit further study.

PMID- 7527293
TI  - Risperidone in the treatment of pervasive developmental disorder.
AB  - Elevated concentrations of blood serotonin have been documented in autistic
      children and mentally retarded adults. Antiserotonergic pharmacotherapy has been
      partially effective in treating a subgroup of children with autistic disorder.
      Therefore, the possibility is raised that an antiserotonergic treatment may be of
      value to adult psychiatric patients with a history of pervasive developmental
      disorder. Two such cases are described where the patients underwent psychiatric
      and neuropsychological examination before and after treatment with risperidone, a
      potent 5-HT2 antagonist with additional D2 antagonistic properties. Particular
      improvements were documented in both patients, despite long histories of
      cognitive compromise and high likelihood of damage to the central nervous system.

PMID- 7527295
TI  - Molecular characterization of prostate-specific antigen messenger RNA expressed
      in breast tumors.
AB  - Prostate-specific antigen (PSA) is considered a highly specific biochemical
      marker of the prostate gland and is currently used for prostate cancer diagnosis
      and monitoring of patients with prostate adenocarcinoma. We recently
      demonstrated, however, that about 30% of female breast tumors produce a M(r)
      33,000 protein that has striking similarities to seminal PSA. In this study we
      characterized the presence of PSA in 6 breast tumors and in the testosterone
      stimulated T47D breast cancer cell line at the mRNA level. Using reverse
      transcriptase-polymerase chain reaction and DNA sequencing techniques we
      identified PSA mRNA in immunoreactive PSA-positive breast tumors but not in
      immunoreactive PSA-negative breast tumors. The sequence of the generated
      polymerase chain reaction products was identical to the sequence of the PSA
      complementary DNA derived from prostate tissue. The data presented here support
      the notion that breast tumors produce a M(r) 33,000 protein which is identical to
      PSA produced by the prostate gland. Our study suggests that the presence of PSA
      in breast tumors may be used as a new additional biochemical marker for breast
      cancer prognosis, for the spreading of hematogenous micrometastases, and/or for
      response to adjuvant treatment.

PMID- 7527296
TI  - Characterization of poliovirus replicons encoding carcinoembryonic antigen.
AB  - Recombinant vaccines hold great promise for the prevention and therapy of
      infections diseases and cancer. We have explored the use of poliovirus as a
      recombinant vector to deliver genes into cells for the purpose of vaccination.
      For our studies, we have chosen to express the gene-encoding carcinoembryonic
      antigen (CEA) using a novel poliovirus vector. We have constructed a recombinant
      CEA-poliovirus replicon in which the CEA gene was substituted for the poliovirus
      capsid gene. Following in vitro transcription, the RNA was transfected into cells
      to demonstrate CEA expression. We found that a genome in which the region
      encoding the signal sequence of the CEA protein (amino acids 1-34) was removed
      was replication competent (i.e., referred to as a replicon). We encapsidated the
      CEA-poliovirus replicon by transfecting this RNA into cells previously infected
      with a recombinant vaccinia virus (VV-P1) which expresses the poliovirus capsid
      protein (P1). Serial passage in the presence of VV-P1 resulted in the generation
      of stocks of these encapsidated replicons. Infection of cells with the
      encapsidated replicon containing the CEA-poliovirus genome resulted in expression
      of the CEA protein. To test immunogenicity, mice susceptible to poliovirus were
      given three doses of the encapsidated replicons via the i.m. route. By the third
      administration, a CEA-specific antibody response was detected. Potential future
      use of the poliovirus replicon system as both a parenteral and oral vaccine
      vector is discussed.

PMID- 7527297
TI  - Nodularin, a potent inhibitor of protein phosphatases 1 and 2A, is a new
      environmental carcinogen in male F344 rat liver.
AB  - Nodularin and microcystin-LR are cyanobacterial toxins and environmental hazards.
      Nodularin inhibits protein phosphatases 1 and 2A with the same potency as does
      microcystin-LR, which has recently been identified as a potent tumor promoter in
      rat liver. Our results suggested that nodularin is also a new tumor promoter in
      rat liver. A two-stage carcinogenesis experiment in rat liver initiated with
      diethylnitrosamine and without partial hepatectomy revealed that nodularin
      stimulated glutathione S-transferase placental form-positive foci in rat liver
      more effectively than did microcystin-LR, and that nodularin alone induced
      glutathione S-transferase placental form-positive foci as well as did
      diethylnitrosamine alone. Thus, nodularin itself is a new liver carcinogen, and
      microcystin-LR is a tumor promoter rather than a carcinogen. Nodularin induced
      hyperphosphorylation of cytokeratin peptides 8 and 18 in primary cultured rat
      hepatocytes 20% more effectively than did microcystin-LR, suggesting that
      nodularin penetrates more easily into the hepatocytes than does microcystin-LR.
      Nodularin up-regulated induction of c-jun, jun-B,jun-D,c-fos,fos-B, and fra-1
      mRNA transcripts in rat liver after i.p. administration, and the accumulation of
      the mRNA transcripts was sustained for over 9 h after treatment. The
      environmental hazards of cyanobacterial toxins are discussed in relation to human
      primary liver cancer in Qidong county in the People's Republic of China. Our
      results support this hypothesis and indicate the need for prevention measures
      against cyanobacterial toxins.

PMID- 7527298
TI  - Specificity and longevity of antitumor immune responses induced by B7-transfected
      tumors.
AB  - We have shown previously that expression of the costimulatory ligand B7.1 by the
      UV-induced melanoma K1735 leads to rejection of the tumor by syngeneic hosts and
      the induction of immunity to challenge by the parental B7-negative tumor. Here we
      extend our analysis of the effectiveness of B7-positive tumor cells as vaccines
      to additional tumor models and analyze the protective immunity in detail. We have
      found that the immunity induced by K1735 is not restricted to the parental tumor
      cells but is effective against an additional melanoma line and an unrelated
      fibrosarcoma as well. This immunity is, however, relatively short-lived, and no
      significant protection is observed after 90 days. Depletion of CD4+ T cells prior
      to rechallenge has no significant effect on the subsequent rejection of B7
      negative tumor cells. EL-4 thymoma cells transfected with B7.1 are also
      effectively rejected, and mice which have rejected B7 + EL-4 cells are immune to
      challenge with not only EL-4, but also reject an unrelated thymoma, C6VL. In
      contrast to the short-lived immunity observed in the melanoma model, mice are
      effectively protected against challenge with EL-4 for longer than 90 days after
      rejection of B7 + EL-4. Finally, we show that irradiation severely diminishes the
      effectiveness of B7-positive tumor cells as immunogens. This work has
      implications for the use of B7-positive cells as tumor vaccines.

PMID- 7527299
TI  - Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma
      cell line reduces primary tumor growth, metastatic potential, and angiogenesis.
AB  - Previous studies demonstrated that metastatic MDA-MB-435 breast carcinoma cells
      synthesized and secreted less of the extracellular matrix protein thrombospondin
      1 (TSP1) than nonmetastatic breast carcinoma cell lines, a trend also observed
      for melanoma and lung carcinoma cell lines. To directly examine the effect of
      tumor cell TSP1 expression on tumor growth and metastasis. MDA-MB-435 cells were
      transfected with full length THBS-1 cDNA linked to a constitutive cytomegalovirus
      promoter, or with the cytomegalovirus vector alone. Injection of transfected
      clones that overexpressed TSP1 into the mammary fat pad of nude mice resulted in
      a dose-dependent inhibition of primary tumor size and an inhibition of
      spontaneous pulmonary metastases, which occurred in 21-30% of THBS-1
      transfectants compared to 44-49% of controls (P = 0.007). An additional clone was
      identified that overexpressed a COOH-terminally truncated TSP1. This clone
      produced larger primary tumors and an increase in the occurrence of metastases
      relative to control transfectants, suggesting the participation of a previously
      understudied region of TSP1 in the regulation of tumor progression. The THBS-1
      and control transfectants did not exhibit significant differences in growth,
      colonization, or motility in vitro. However, a relative reduction in capillary
      densities in primary tumors formed by the wild-type THBS-1 transfectants was
      observed, suggestive of an angiostatic effect. The data indicate that tumor cell
      production of TSP1 can exert a significant inhibitory effect on tumor progression
      in the MDA-MB-435 breast carcinoma cell line, which may be attributable in part
      to a reduction in angiogenesis.

PMID- 7527302
TI  - [A murine model of mammary adenocarcinoma (VI TA2MA-891) with high rate of
      spontaneous metastases in the lungs].
AB  - The primary donor tumor was a spontaneous mammary tumor which arose in a 348-day
      old female TA2 mouse. The pedigree number of that mouse was 0901-1423. The mouse
      was sacrificed for serial s.c. transplantation with 3 isogeneic hosts on January
      19, 1989 and a total of 27 generations succeeded by the end of April, 1992. The
      primary donor tumor was diagnosed pathologically as a type B mouse mammary
      adenocarcinoma (Dunn 1959). The incidence of this serial s.c. transplantation
      tumor is 100% after inoculation. The latency period is 4-7 days and the lifetime
      of tumorbearing mice is about 47 days. The spontaneous metastatic rates in the
      lungs was 100% after the 11th generations. The earliest metastasis seen in the
      lung under light microscopy was on the 10th day after inoculation, and the
      earliest seen by gross examination was on about the 35th day. The transplanted
      tumor grew slowly from the 4th day to the 21st day after inoculation and then
      grew rather fast from the 22nd to the 47th day. The average size of the
      transplanted tumor obtained from 10 recipient mice on the 47th day after
      inoculation was 4.93cm3. Seven anticancer drugs were administered respectively
      for a sensitivity test. The taking rates of the transplanted tumor using 4 of the
      7 drugs were as follows: 5-fluorouracil 29.27% (P < 0.05); thio-tepa 44.80% (P <
      0.01); cyclophosphamide 95.31% (P < 0.01); and bleomycin 96.27% (P <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527300
TI  - Episomal expression of sense and antisense insulin-like growth factor (IGF)
      binding protein-4 complementary DNA alters the mitogenic response of a human
      colon cancer cell line (HT-29) by mechanisms that are independent of and
      dependent upon IGF-I.
AB  - HT-29 cells express and secrete insulin-like growth factor (IGF)-II and only one
      of the six IGF-binding proteins, IGFBP-4. In the present study, the physiological
      role of endogenous IGFBP-4 in regulating the growth response of HT-29 cells to
      exogenous and endogenous IGFs was examined. Both the basal and the IGF-stimulated
      growth of HT-29 cells was significantly increased over control values in the
      presence of IGFBP-4 antibody, suggesting that endogenous IGFBP-4 is a potent
      inhibitor of the mitogenic effects of endogenous and exogenous IGFs. In order to
      further confirm the inhibitory role of endogenous IGFBP-4, sense and antisense
      complementary DNA fragments of human IGFBP-4 were ligated into an episomal
      mammalian expression vector (pCEP4). Restriction mapping and Southern blot
      analysis were used to confirm directional cloning of the IGFBP-4 complementary
      DNA fragments in the sense and antisense directions in the pCEP4 vectors. HT-29
      cells were transfected with either the control (no insert, C-P), sense (S-P), or
      antisense (AS-P) vectors and subjected to hygromycin selection. The functional
      nature of the transfectants was confirmed by measuring IGFBP-4 concentrations in
      the conditioned media (CM) of 10(7) cells by ligand and immunoblot analysis.
      IGFBP-4 concentrations were 7.4 +/- 1.7-fold higher in the CM of S-P cells
      compared to that in the CM of C-P cells, while IGFBP-4 concentrations in the CM
      of AS-P cells were significantly lower than those present in the CM of C-P cells.
      Both the basal and the IGF-I-stimulated growth of the AS-P cells was
      significantly higher than that of the C-P and S-P cells. The basal (non
      stimulated) and the IGF-I-stimulated growth of the S-P cells was not
      significantly different from that of the C-P cells, suggesting that
      overexpression of IGFBP-4 was not inhibitory to the growth of the HT-29 cells.
      The basal growth of the S-P and C-P cells was significantly increased in the
      presence of IGFBP-4 antibody, once again suggesting that endogenous IGFBP-4 was a
      potent inhibitor of autocrine effects of endogenous factors (IGF-II). Addition of
      IGFBP-4 antibody had no significant effect on the basal growth of the AS-P cells,
      confirming that the difference between the growth response of the AS-P, C-P, and
      S-P cells was largely contributed by the difference in the endogenous secretion
      of IGFBP-4 by the cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7527301
TI  - Anti-(glioma surface antigen) monoclonal antibody G-22 recognizes overexpressed
      CD44 in glioma cells.
AB  - We raised an anti-glioma monoclonal antibody, named G-22, that specifically
      recognizes a human glioma-associated surface antigen. Proven to be useful for
      target imaging of malignant gliomas after radioisotope labeling and cerebrospinal
      fluid diagnosis by enzyme-linked immunospecific assay, G-22 was found to
      immunoprecipitate an 85-kDa glycoprotein of the human glioma U-251MG cell. We
      purified this antigen by G-22-coupled cyanogenbromide-activated Sepharose
      affinity chromatography, and sequence analysis demonstrated that the 54 amino
      acid residues were identical to positions 55-108 of human CD44. The results show
      that the smallest spliced form (85 kDa) of CD44 is strongly expressed in glioma
      cells.

PMID- 7527303
TI  - Positive interactions between human interferon and cepharanthin against human
      cancer cells in vitro and in vivo.
AB  - A human tumor microcytotoxicity-viable cell-staining assay was used to test the
      antiproliferative effect of recombinant human interferon-beta or -gamma alone and
      in combination with bisbenzylisoquinoline alkaloid cepharanthin against four
      human tumor cell lines in vitro and in nude mice. Results obtained in the in
      vitro study indicate that combinations of interferon-beta/-gamma with
      cepharanthin show synergistic and, occasionally, additive antiproliferative
      effects in a dose-dependent manner on tumor viable cell-staining assay.
      Interferon-gamma combined with cepharanthin suppressed the growth of all four
      human tumor cell lines (RPMI 4788, PC 10, HeLa, ZR-75-1), and this enhanced
      antiproliferative effect was not dependent on the interferon species involved,
      including interferon-beta and -gamma. In an experimental model of pulmonary
      metastasis, in which human colon tumor cells were inoculated i.v. into nude mice,
      interferon-gamma alone exerted significant inhibitory activity against pulmonary
      metastasis in a dose-dependent manner, and cepharanthin alone also significantly
      inhibited metastasis. Furthermore, a combination of interferon-gamma with
      cepharanthin resulted in a considerable suppression of pulmonary metastasis.
      These studies indicate that due to their therapeutic potential, combinations of
      recombinant human interferon-beta or -gamma with cepharanthin might be a
      promising therapy for pulmonary metastasis of human cancers.

PMID- 7527305
TI  - FK-506 therapeutic drug monitoring.

PMID- 7527304
TI  - Biologic agents as biochemical modulators: pharmacologic basis for the
      interaction of cytotoxic chemotherapeutic drugs and interferon.
AB  - Biochemical modulation of cytotoxic cancer chemotherapeutic agents is one means
      of enhancing the activity and selectivity of antitumor drugs. Traditionally this
      approach has utilized detailed information regarding a particular enzymatic
      reaction or biochemical pathway to develop potential modulating agents. In
      contrast, the reported clinical therapeutic activity of IFN in combination with
      cytotoxic agents has prompted a reexamination of the biochemical actions of the
      cytokine. Interferon elicits a number of cellular actions that might contribute
      to its pharmacologic activity, including both direct antitumor effects and host
      mediated actions. The best understood are those related to the cytotoxicity of
      the fluoropyrimidine antimetabolites and include enzymatic reactions involved in
      fluoropyrimidine metabolic activation, catabolism, and interaction with its
      target enzyme. However, even in this instance, a mechanistic association of a
      specific pharmacologic action with therapeutic activity remains to be determined.
      These studies demonstrate that cytokines and other biologic agents may exert
      specific biochemical modulations that augment (or potentially attenuate) the
      activity of the cytotoxic chemotherapeutic agents.

PMID- 7527306
TI  - Plasma vs whole blood for therapeutic drug monitoring of patients receiving FK
      506 for immunosuppression.
AB  - By retrospective analysis of 13,000 blood samples obtained from 248 patients
      receiving FK 506 therapy, we compared the suitability of plasma with that of
      whole blood as the matrix for therapeutic drug monitoring of FK 506. The plasma
      concentrations did not correlate with the concentrations in whole blood (r =
      0.56). In contrast to plasma samples (analyzed by enzyme immunoassay), FK 506 was
      detectable in all whole-blood samples (analyzed by enzyme
      immunoassay/microparticle enzyme immunoassay). The inter- and intraindividual
      variations of FK 506 measurements were greater in plasma than in whole blood.
      Moreover, plasma concentrations correlated only poorly with clinical events.
      There was a tendency to greater plasma concentrations being measured during
      episodes of toxicity, but no clear difference was evident between stable course
      and rejection. In whole-blood specimens, a correlation between reduced or
      increased FK 506 concentrations and rejection or toxicity, respectively, was
      observed. The discriminatory power of whole-blood values was greater for the
      differentiation between toxicity and stable course than between rejection and
      stable course. We therefore recommend whole blood rather than plasma as the
      matrix for therapeutic monitoring of FK 506 concentrations.

PMID- 7527308
TI  - Quantification of hemoglobin variants by capillary isoelectric focusing.
AB  - Capillary isoelectric focusing (cIEF) was used to identify and quantify major and
      minor hemoglobin (Hb) variants. Whole blood (approximately 10 microL required)
      hemolysate was analyzed with a commercial instrument equipped with a 50 microns
      (i.d.) x 27 cm coated capillary filled with 20 g/L ampholytes (pH 6-8) in 4 g/L
      methylcellulose (MC). Cathode and anode solutions were 20 mol/L NaOH and 100
      mol/L H3PO4 in MC, respectively. Samples (approximately 40 nL) were applied via
      autosampler by low-pressure injection, focused for 3 min at 30 kV, and mobilized
      by simultaneous voltage and low pressure past the detector, where absorbance at
      415 nm was analyzed by an automated data acquisition system. Blood from subjects
      with sickle cell trait, Hb S/C disease, and various beta-thalassemias were
      analyzed by cIEF in < 15 min. cIEF was used to separate Hb S from Hb D-Los
      Angeles. Assay precision determined with commercial controls gave CV < 2% for Hb
      A and S, and 1-11% for minor Hb variants A2, F, and A1c. Results obtained by cIEF
      for patients' samples agreed well with values determined by conventional assays
      (r2 > 0.95). The results demonstrate that cIEF is a rapid, sensitive, high
      resolution automated method for routine quantitative clinical analysis of Hb
      variants.

PMID- 7527309
TI  - Immunological recognition and clinical significance of nicked human chorionic
      gonadotropin in testicular cancer.
AB  - We studied the physical properties, immunological recognition, and clinical
      significance of nicked human chorionic gonadotropin (hCGn) in testicular cancer.
      Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing
      conditions, the beta-subunit of hCGn (hCG beta n) dissociated into two peptides,
      and, by reversed-phase chromatography, hCG beta n was found to be less
      hydrophobic than hCG beta. Immunologically, hCGn lacked two epitopes specific for
      holo-hCG (c1, c2), whereas at least five hCG beta epitopes (beta 1-beta 5) were
      preserved, and, as a result, recognition of hCGn by different hCG assays varied
      widely. In 309 sera and 88 urine samples from patients with seminomatous or
      nonseminomatous testicular cancer, hCG-only, hCG+hCGn, and hCG+hCGn+hCG beta+hCG
      beta n+hCG beta core-fragment assays gave parallel results. hCGn was more
      abundant in urine than in serum samples. In conclusion, hCGn lacks two
      conformationally dependent epitopes of hCG, causing a change in hydrophobicity
      and explaining its failure to react in certain holo-hCG assays. Recognition of
      hCGn, however, does not seem to be crucial in the routine use of serum hCG as a
      tumor marker in patients with testicular cancer.

PMID- 7527307
TI  - Detection of autoantibodies to amylase by ELISA: comparison of detection of
      macroamylase and free autoantibody.
AB  - New ELISAs for detecting macroamylase or free autoantibodies to amylase were
      tested with 48 samples that had been characterized by gel chromatography and
      electrophoresis. The macroamylase ELISA, with anti-IgG or anti-IgA for detection,
      detected macroamylase in 28 of 33 samples known to contain macroamylase (85%
      sensitivity), whereas the ELISA for free autoantibody to amylase was positive for
      only 11 samples. Specificities of both ELISAs were 93%. Among 28 true positives
      detected with the macroamylase ELISA, 22 contained IgA, 3 contained IgG, and 3
      contained both immunoglobulins. Detection of IgM added no true positives. ELISA
      responses (y) were proportional to log [macroamylase concentration by
      chromatography (x)] from 0 to 1200 U/L: y = 5.15 x + 1.66; r = 0.72; Sy x = 1.65.
      As new tools for detecting macroenzymes consisting of enzyme-autoantibody
      complexes, the ELISAs show that some autoantibodies are detected more sensitively
      as antibody-antigen complexes than as free antibody.

PMID- 7527310
TI  - Rapid detection of 1078 delT mutation by PCR-mediated site-directed mutagenesis:
      detection of cystic fibrosis carriers in a celtic population.

PMID- 7527311
TI  - Evaluation of tumor-associated antigen (2H6 antigen) in detecting early stages of
      gastric cancer.
AB  - A sandwich enzymed-linked immunosorbent assay (ELISA) was developed by using
      monoclonal antibody 2H6 (2H6 MoAb). MoAb 2H6 could be used to detect the 2H6
      antigen in the sera of several cancers, showing positive rates of 65.4%, 66.7%,
      47.4%, 80.0%, 45.2% and 16.7% in gastric cancer, hepatocellular carcinoma,
      cancers of the colon, esophagus, breast and pancreas, respectively. On the other
      hand, the positive rates in benign diseases or healthy donors were 3.4%, 3.4%,
      4.2%, 8.3%, 6.9%, and 1.2% in myasthenia gravis, polymyositis, gastritis, gastric
      ulcer, other benign diseases and normal healthy donors, respectively. Fifty-two
      patients with gastric cancer were investigated in detail. The positive rates of
      serum 2H6 antigen, CEA, AFP, CA19-9 and CA125 in patients with gastric cancer
      were 65.4%, 9.6%, 2.3%, 25.0% and 8.1%, respectively. Among these tumor markers,
      serum 2H6 antigen levels alone were significantly elevated in patients with early
      stage (I and II) gastric cancer. Furthermore, combining the measurement for serum
      2H6 with CA19-9 increased the percentage of gastric cancer slightly. No
      correlation between 2H6 antigen and these other tumor markers was observed. The
      serum levels of 2H6 antigen were monitored post-surgically in 11 patients for 12
      weeks and they were found to diminish gradually. The findings suggest that the
      measurement of serum 2H6 antigen may be a useful marker for an early stage of
      gastric cancer.

PMID- 7527312
TI  - Simultaneous detection of delta F508, G542X, N1303K and 1717-1G-->A mutations in
      cystic fibrosis by capillary electrophoresis in polymer networks.

PMID- 7527313
TI  - Metal stents for malignant biliary obstruction.
AB  - The main problem in the palliative treatment of malignant biliary obstruction is
      recurrent jaundice and cholangitis due to clogging of the endoprostheses. Large
      bore metal stents, which can be placed using small-sized delivery systems, have
      been recognized as an important gain. Their use has facilitated the percutaneous
      drainage procedure. The long-term patency rates of both endoscopically and
      percutaneously placed metal stents seem to be better than those of conventional
      stents. Although the long-term economical aspects are in favor of metal stents
      due ot the decreased need for readmissions and reinterventions, the high initial
      costs of metal stents constitute the main obstacle to their wide-spread use.

PMID- 7527314
TI  - DNA strand breakage and DNA structure influence staining with propidium iodide
      using the alkaline comet assay.
AB  - The alkaline comet assay is used to detect DNA single-strand breaks in individual
      cells embedded in agarose, lysed to denature DNA and remove proteins, and briefly
      exposed to an electric field to allow broken DNA to migrate. Total DNA
      fluorescence, measured by staining individual comets with propidium iodide, is
      reduced 30-40% by low doses of ionizing radiation, N-methyl-N-nitrosoguanidine
      (MNNG), etoposide, or hydrogen peroxide. Three possible explanations were
      examined: 1) these agents produce small fragments of DNA that are lost during
      lysis and electrophoresis, 2) the analysis of comet images is less efficient once
      the DNA is small enough to migrate in the electric field, and 3) DNA staining by
      propidium iodide is affected by changes in DNA structure caused by strand breaks
      and exposure to alkali. Our results indicate that the decrease in fluorescence
      after low doses is best explained by a change in ability of DNA, which has been
      denatured by alkali and subsequently renatured, to interact with fluorescent
      dyes. This change in fluorescence has the practical consequence of improving the
      ability of the alkaline comet assay to distinguish damaged from undamaged cells.

PMID- 7527315
TI  - Fast kinetic measurements and on-line dilution by flow injection cytometry.
AB  - An improved flow injection cytometry (FIC) system suitable for fast cellular
      kinetic measurements and on-line dilution is described. The instrument allows for
      measurements from 1.2 s (+/- 0.05 s) after the initiation of mixing, up to any
      time thereafter. Crucial factors in determining fast kinetic measurements, such
      as the displacement volume for sample introduction, rate of transport to
      cytometric interrogation point, and the mixing speed are evaluated and discussed.
      By varying the volume aspirated, this instrument can facilitate the dilution of
      cells and/or reagent over a range of one order of magnitude. The fast kinetic and
      on-line dilution capabilities were demonstrated by on-line staining of DNA in
      trout erythrocytes with 4',6-diamidino-2-phenylindole (DAPI). The utility of the
      instrument for measurement of enzyme kinetics was illustrated using human
      lymphocytes, measuring the glutathione S-transferase (GST) catalyzed reaction
      between monochlorobimane (MCB) and glutathione (GSH).

PMID- 7527316
TI  - Evaluation of interspecific DNA content variations and sex identification in
      Falconiformes and Strigiformes by flow cytometric analysis.
AB  - A high interspecific karyotype variability has been evidenced in birds especially
      in Falconiformes and Strigiformes. Avian cytogenetic analysis, conventionally
      used for this study, presents several difficulties. We used flow cytometric
      analysis in order to obtain further information on the DNA patterns of different
      species of birds belonging to the above-mentioned orders. Our study was performed
      on blood samples while chicken erythrocytes and human lymphocytes, with known
      cytometric DNA content, were used as reference cells. The blood samples of the
      birds under study were stained, simultaneously to the reference cell, with a
      lysis-staining buffer containing propidium iodide. The nuclear DNA content of the
      bird samples was calculated as DNA index in relation to reference cells, and was
      expressed as nuclear DNA mass in picograms (pg) with respect to the standard
      value of 7.0 pg per human lymphocyte nucleus. The results obtained showed an
      interspecific variability of DNA content and evidenced the usefulness of FCM
      analysis as a rapid and easy tool for studying the DNA pattern of different
      species of birds. Moreover, our results have confirmed and extended the
      possibility of sex identification in species of birds characterized by sexual
      monomorphism by evaluating the small DNA content difference which exists between
      males and females.

PMID- 7527317
TI  - Reversing the effect of formalin on the binding of propidium iodide to DNA.
AB  - Formalin, an excellent preservative of cellular morphology, is a commonly used
      fixative for tissue specimens in hospital pathology laboratories. This preserved
      material is a potential source of tissue for diagnostic and retrospective
      research studies on DNA using flow cytometry. Unfortunately, formalin interferes
      with the binding of propidium iodide (PI) and other fluorescent dyes to DNA, thus
      altering the measurement of DNA content by flow cytometry or image analysis. This
      interference has been attributed to the cross-linking of histones by formalin.
      Since formalin alters the measurement of DNA content in formalin-fixed and
      formalin-fixed, paraffin-embedded tissues, this study was designed to explore the
      use of various physicochemical methods to reverse the effect of the formalin on
      the binding of PI to DNA. This study demonstrates that resuspending formalin
      fixed cells in PBS and heating them at 75 degrees C for at least 1 h prior to
      staining with PI restores the staining of the DNA to approximately the same
      fluorescence intensity as that of fresh tissue.

PMID- 7527318
TI  - [Detection of Tropheryma whippelii using the polymerase chain reaction before and
      after therapy of Whipple's disease].

PMID- 7527322
TI  - Optimum outpatient therapy of skin and skin structure infections.
AB  - Skin and skin structure infections appear in a variety of ways with multiple
      aetiologies. Optimum therapy is accomplished with a good understanding of both
      skin anatomy and common resident or transient bacterial flora present on the skin
      surface. Primary and secondary infections occur in both immunocompetent and
      immunocompromised patients, each of which require unique decision-making skills
      on the part of the prescriber. Deciding when culture and sensitivity should be
      performed or therapy should be begun empirically is often difficult and can be
      frustrating. This is complicated by the ever-increasing number of antimicrobial
      agents available today and their variable costs. Choosing the best antibiotic
      agent, based on evidence of which is the most effective agent for a particular
      lesion, the easiest dosage schedule and the most economical drug, is a goal that
      will best serve both the patient and the physician.

PMID- 7527319
TI  - Is the development of antibodies to streptokinase clinically relevant?

PMID- 7527320
TI  - The clinical potential of ademetionine (S-adenosylmethionine) in neurological
      disorders.
AB  - This review focuses on the biochemical and clinical aspects of methylation in
      neuropsychiatric disorders and the clinical potential of their treatment with
      ademetionine (S-adenosylmethionine; SAMe). SAMe is required in numerous
      transmethylation reactions involving nucleic acids, proteins, phospholipids,
      amines and other neurotransmitters. The synthesis of SAMe is intimately linked
      with folate and vitamin B12 (cyanocobalamin) metabolism, and deficiencies of both
      these vitamins have been found to reduce CNS SAMe concentrations. Both folate and
      vitamin B12 deficiency may cause similar neurological and psychiatric
      disturbances including depression, dementia, myelopathy and peripheral
      neuropathy. SAMe has a variety of pharmacological effects in the CNS, especially
      on monoamine neurotransmitter metabolism and receptor systems. SAMe has
      antidepressant properties, and preliminary studies indicate that it may improve
      cognitive function in patients with dementia. Treatment with methyl donors
      (betaine, methionine and SAMe) is associated with remyelination in patients with
      inborn errors of folate and C-1 (one-carbon) metabolism. These studies support a
      current theory that impaired methylation may occur by different mechanisms in
      several neurological and psychiatric disorders.

PMID- 7527323
TI  - Management of toxoplasmosis.
AB  - Toxoplasma gondii, an intracellular coccidian protozoan, is the causative agent
      of toxoplasmosis, a widespread infection affecting various birds and mammals
      including humans. In immunocompetent hosts, the infection is usually asymptomatic
      and benign. Toxoplasmosis is either congenital or acquired. In general, prenatal
      therapy of congenital toxoplasmosis is beneficial in reducing the frequency of
      infant infection. Therapies are based primarily on spiramycin because of the
      relative lack of toxicity and high concentrations achieved in the placenta.
      Clindamycin is the standard drug for chemoprophylaxis in newborn infants, and is
      directed at preventing the occurrence of retinochoroiditis as a late sequel to
      congenital infection. The standard treatment for acquired toxoplasmosis in both
      immunocompetent and immunodeficient patients is the synergistic combination of
      pyrimethamine and sulphonamides. Toxoplasmic encephalitis is the most common
      manifestation of acquired toxoplasmosis in immunocompromised patients and if not
      treated is fatal. However, because of toxicity, the therapeutic efficacy of
      pyrimethamine-sulphonamide combinations may be seriously limited in
      immunodeficient patients. A number of novel and less toxic agents are being
      currently studied in clinical settings, including macrolide antibiotics
      (clindamycin, clarithromycin and azithromycin) and atovaquone, as well as some
      older anti-infective drugs such as cotrimoxazole (trimethoprim/sulfamethoxazole).
      Maintenance or prophylactic therapy is essential in many patients with acquired
      immunodeficiency syndrome (AIDS) where toxoplasmosis is most often the result of
      a pre-existent latent infection.

PMID- 7527324
TI  - Pharmacological management of back pain syndromes.
AB  - The symptom of back pain may be the result of many different pathologies. As
      such, patients with back pain require careful assessment to determine whether the
      cause is from the spine or other systems. For acute mechanical back pain,
      treatment is often symptomatic. Symptomatic treatment may include analgesics,
      anti-inflammatories and/or muscle relaxants. Patients may also need hypnotics in
      the short term to help them sleep at night. However, drug therapy should be
      reduced and stopped as soon as possible. Furthermore, too much bedrest may be
      counterproductive. Paracetamol (acetaminophen) is the standard treatment for
      transient back pain. More severe pain may require the addition of an opioid, such
      as codeine or dextropropoxyphene. Morphine and pethidine (meperidine) may be
      necessary in patients with back pain due to neoplastic disease or osteoporotic
      fracture. However, the opioid analgesics are associated with dependence,
      tolerance and adverse effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) have
      analgesic efficacy comparable with paracetamol. Individual patients respond
      differently to different NSAIDs, and several agents may have to be tried. Long
      term therapy with NSAIDs is necessary in diseases with an inflammatory component
      such as ankylosing spondylitis. Calcitonin reduces bone resorption and bone blood
      flow, and has been suggested to have central analgesic effects. As such, it has
      been used successfully in patients with Paget's disease, osteolytic bone disease
      and osteoporosis. Bisphosphonates also inhibit osteoclastic bone resorption and
      may be useful in Paget's disease, osteolytic metastases and osteoporotic
      fractures. Other drugs which may be useful in relieving back pain associated with
      specific circumstances include the tricyclic antidepressants, anxiolytics,
      antiepileptic agents, corticosteroids, colchicine and chymopapain.

PMID- 7527321
TI  - New anticonvulsant drugs. Focus on flunarizine, fosphenytoin, midazolam and
      stiripentol.
AB  - In the past decade, several new antiepileptic drugs have been tested. Most
      recently, 5 new antiepileptic drugs have been launched onto European and US
      markets. These include vigabatrin, oxcarbazepine and lamotrigine in Europe, and
      felbamate and gabapentin in the US. In addition to these, 3 additional drugs are
      in the clinical investigational stage: flunarizine, fosphenytoin and stiripentol.
      A fourth agent is midazolam, which was originally introduced in 1986, but
      recently has shown effectiveness in the treatment of status epilepticus.
      Flunarizine is a selective calcium channel blocker that has shown anticonvulsant
      properties in both animal and human studies. It is a long-acting anticonvulsant
      that clinical studies have shown to have effects similar to those of phenytoin
      and carbamazepine in the treatment of partial, complex partial and generalised
      seizures. Fosphenytoin was developed to eliminate the poor aqueous solubility and
      irritant properties of intravenous phenytoin. It is rapidly converted to
      phenytoin after intravenous or intramuscular administration. In clinical studies,
      this prodrug showed minimal evidence of adverse events and no serious
      cardiovascular or respiratory adverse reactions. It may have a clear advantage
      over the present parenteral formulation of phenytoin. Midazolam is a
      benzodiazepine that is more potent than diazepam as a sedative, muscle relaxant
      and in its influence on electroencephalographic measures. It has been shown to be
      an effective treatment for refractory seizures in status epilepticus. Stiripentol
      has anticonvulsant properties as well as the ability to inhibit the cytochrome
      P450 system. There are significant metabolic drug interactions between
      stiripentol and phenytoin, carbamazepine and phenobarbital (phenobarbitone).
      Stiripentol has been studied in patients with partial seizures, refractory
      epilepsy and refractory absence seizures with some efficacious results.

PMID- 7527325
TI  - Foscarnet. A reappraisal of its antiviral activity, pharmacokinetic properties
      and therapeutic use in immunocompromised patients with viral infections.
AB  - The DNA polymerase of human herpes viruses, including cytomegalovirus (CMV), and
      the reverse transcriptase of human immunodeficiency virus (HIV) are selectively
      inhibited in vitro by the pyrophosphate analogue foscarnet. Inhibition is
      reversible on withdrawal of foscarnet and additive or synergistic effects have
      been demonstrated in vitro with other antiviral drugs, including ganciclovir and
      zidovudine. Foscarnet appears to have negligible effects on host enzymes and
      cells. Complete or partial clinical resolution of ocular symptoms is obtained in
      more than 89% of patients with acquired immunodeficiency syndrome (AIDS) and CMV
      retinitis during foscarnet induction therapy, but relapse occurs soon after
      ceasing treatment. Maintenance treatment given daily can extend the period of
      remission considerably. Foscarnet and ganciclovir monotherapy had similar
      efficacy in the treatment of CMV retinitis in patients with AIDS in several
      studies, and have been used concomitantly in immunocompromised patients with
      recalcitrant CMV infections. In 1 trial, patients receiving foscarnet survived
      for significantly longer than those receiving ganciclovir. Foscarnet has been
      used successfully in the treatment of limited numbers of immunocompromised
      patients with CMV-associated gastrointestinal (improvement in over 67% of
      patients) and other infections. Aciclovir-resistant herpes simplex infections in
      immunocompromised patients have also been treated successfully with foscarnet.
      Almost 90% of a foscarnet dose is excreted in the urine. Reversible
      nephrotoxicity is common during foscarnet therapy, but may be reduced by dosage
      adjustment and adequate hydration. Anaemia, nausea and vomiting, disturbances in
      electrolyte levels and genital ulceration have also been associated with
      administration of the drug. The different tolerability profiles of foscarnet and
      zidovudine facilitate the use of these agents in combination in patients with
      AIDS and CMV infection; whereas ganciclovir, like zidovudine, is associated with
      dose-limiting haematological toxicity. The apparent survival benefits seen in
      these patients when receiving foscarnet and zidovudine (possibly linked to
      synergy between zidovudine and foscarnet and/or the inherent anti-HIV activity of
      foscarnet), appear to offer potentially important advantages for foscarnet over
      ganciclovir in the treatment of selected patients with AIDS and CMV infections.

PMID- 7527330
TI  - Interactions between insulin-like growth factor-I (IGF-I) and the system of
      plasminogen activators and their inhibitors in the control of IGF-binding protein
      3 production and proteolysis in human osteosarcoma cells.
AB  - Limited proteolysis in vivo of insulin-like growth factor-binding protein-3
      (IGFBP-3) by as yet unidentified serine proteases plays a key role in controlling
      the bioavailability of IGFBP-3-associated insulin-like growth factors (IGFs).
      Both the IGF system and the system of plasminogen activators (PAs) and their
      inhibitors (PAIs) are involved in bone remodeling, and plasmin has been shown to
      provoke dissociation of IGFBP-IGF complexes in cultured MG-63 human osteoblasts.
      The aim of this work was to investigate interactions between IGF-I and the PA/PAI
      system and their influence on IGFBP-3 production and proteolysis in this cell
      model. At confluency, MG-63 cells maintained for 3 days in serum-free medium
      constitutively secreted IGFBP-2 and small amounts of IGFBP-3 and IGFBP-4. As
      shown by Western ligand and immunoblot analyses of the culture medium and
      Northern blot analysis of IGFBP-3 messenger RNA, production of these IGFBPs, and
      of IGFBP-3 in particular, was dose dependently stimulated by the addition of 12.5
      100 ng/ml recombinant human (rh) IGF-I. Increasing concentrations of plasminogen
      (0.05-3.5 micrograms/ml) added during the final 12 h of culture reduced the
      amounts of IGFBP detectable by Western ligand blotting, especially IGFBP-3. This
      reduction reflected proteolysis, as shown by immunoblotting, which revealed 30-,
      20-, and 16-kilodalton fragments of IGFBP-3. In the presence of 25 ng/ml IGF-I,
      which stimulated IGFBP-3 production, proteolysis was reduced by approximately
      half. Incubation of glycosylated [125I]rh-IGFBP-3 as substrate in cell-free
      conditioned medium gave the same results. Addition of 50 ng/ml rhIGF-I to
      conditioned medium (to promote IGFBP-3-rhIGF-I complex formation) failed to
      diminish plasmin-induced proteolysis of IGFBP-3. Urokinase PA activity in the
      conditioned medium decreased significantly when the cells were cultured with
      rhIGF-I, indicating a direct action of IGF-I on urokinase PA and/or PAI
      production. Our results support the notion of a regulation loop whereby IGF-I
      controls its own bioavailability via its action on both IGFBP-3 production and
      the PA/PAI system, which regulates IGFBP-3 proteolysis. The proteolytic cleavages
      of IGFBP-3 caused by plasmin were the same as those caused in vivo by serine
      protease acting on this IGFBP.

PMID- 7527328
TI  - Lacidipine. A review of its pharmacodynamic and pharmacokinetic properties and
      therapeutic potential in the treatment of hypertension.
AB  - Lacidipine is an orally administered calcium channel blocker of the
      dihydropyridine class, which shows selectivity for vascular smooth muscle over
      cardiac tissue and has a long duration of action. In studies using ambulatory
      blood pressure monitoring, lacidipine 2 to 8mg administered once daily in the
      morning reduced blood pressure over 24 hours, with the reductions being greater
      during the day than at night in some studies. 77 to 87% of patients with mild to
      moderate hypertension had their blood pressure controlled by treatment with
      lacidipine 2 to 8 mg/day for 1 to 4 months in dose-finding studies. When
      administered once daily, lacidipine 4 to 6 mg was equivalent in antihypertensive
      efficacy to hydrochlorothiazide 25 to 50 mg/day, atenolol 50 to 100 mg/day, and
      the prototype calcium channel blocker nifedipine 20 to 40 mg twice daily
      (sustained-release formulation). The adverse effects of lacidipine are those
      common to other dihydropyridine calcium channel blockers, and include headache,
      flushing, ankle oedema, dizziness and palpitations. The long term effects of
      lacidipine on cardiovascular morbidity and mortality, and possible additional
      clinical benefits in terms of its antiatherosclerotic effects, are under
      investigation; the outcome of these studies will be important in defining the
      future role of this agent in the treatment of hypertension. Thus, available
      evidence suggests lacidipine provides a further alternative to the
      dihydropyridine calcium channel blockers currently available for the treatment of
      essential hypertension.

PMID- 7527327
TI  - Risperidone. A review of its pharmacology and therapeutic potential in the
      treatment of schizophrenia.
AB  - Risperidone, a benzisoxazol derivative, is a novel antipsychotic agent which
      combines potent serotonin (5-hydroxytryptamine) 5-HT2 and dopamine D2 receptor
      antagonism. Development of the drug was stimulated by reports that the selective
      serotonin 5-HT2 antagonist ritanserin improved the negative symptoms of
      schizophrenia and decreased extrapyramidal symptoms when combined with
      haloperidol. The relatively low incidence of extrapyramidal symptoms with
      risperidone may reflect a preferential action on mesolimbic rather than
      nigrostriatal dopaminergic pathways. Recent clinical investigation suggests that
      risperidone is of at least comparable efficacy to haloperidol and perphenazine in
      improving the symptoms of acute and chronic schizophrenia on short term
      administration. Advantages offered by risperidone over haloperidol include a
      faster onset of antipsychotic action, a lower incidence of extrapyramidal effects
      and possibly greater efficacy against the negative symptoms of schizophrenia. If
      these benefits prove to be maintained during long term therapy, risperidone is
      likely to make a significant contribution to the treatment of schizophrenia.

PMID- 7527332
TI  - Glycosaminoglycans inhibit degradation of insulin-like growth factor-binding
      protein-5.
AB  - Human dermal fibroblasts secrete insulin-like growth factor-binding protein-3
      (IGFBP-3), -4, and -5. Fibroblast-conditioned medium contains minimal intact
      IGFBP-5, and this form of IGFBP is predominantely a 23-kilodalton fragment,
      suggesting that the IGFBP-5 fragment is derived from intact IGFBP-5 by
      proteolysis. In this study we investigated the effects of glycosaminoglycans on
      IGFBP-5 degradation in fibroblast-conditioned medium. The addition of heparin,
      heparan sulfate, and dermatan sulfate (100 micrograms/ml) to the medium of
      fibroblast monolayer cultures inhibited IGFBP-5 degradation, as determined by the
      conversion of intact IGFBP-5 to a 23-kilodalton fragment. In contrast, hyaluronic
      acid, keratan sulfate, and chondroitin sulfate-A and -C had no effect. Heparin
      and heparan sulfate inhibited IGFBP-5 degradation at concentrations of 1 or 2.5
      micrograms/ml, but 100 micrograms/ml dermatan sulfate were required. Heparin was
      also inhibitory in vitro, that is when conditioned medium and heparin were
      incubated without cells. Experiments with modified forms of heparin showed that O
      sulfate groups in the 2 or 3 carbon position were required for heparin to be
      inhibitory. Completely desulfated heparin had no activity, and N-resulfation of
      desulfated heparin had only a minimal effect. Dextran sulfate, pentosan
      polysulfate, and fucoidan, which are composed of different saccharide units but
      contain O-sulfate groups in the 2 or 3 carbon positions, also inhibited IGFBP-5
      degradation. These results demonstrate that heparin-like molecules are important
      regulators of IGFBP-5 degradation. O-Sulfation of the 2 or 3 position of the
      saccharide ring is required for inhibitory activity. As glycosaminoglycan side
      chains are present in proteoglycans that are present in extracellular matrix and
      on cell surfaces, these side-chains represent a potential mechanism for
      regulating IGFBP-5 proteolysis in vivo.

PMID- 7527331
TI  - Regulation in vivo of the acid-labile subunit of the rat serum insulin-like
      growth factor-binding protein complex.
AB  - The acid-labile subunit (ALS) and insulin-like growth factor (IGF)-binding
      protein-3 are glycoproteins that form a complex carrying about 90% of the
      circulating IGFs. This study investigates the regulation of ALS expression by
      Northern hybridization, and serum ALS levels by RIA, in the rat. Northern
      analysis of ALS messenger RNA (mRNA) from adult rat brain, heart, lung, muscle,
      spleen, testis or ovary, kidney, and liver showed a liver-specific predominant 2
      kilobase transcript. The steady state abundance of rat ALS mRNA was greatly
      reduced in neonatal and weanling liver compared to adult liver, with an age
      dependence similar to that of rat serum ALS levels. Fasting for 24 or 48 h
      decreased serum IGF-I and ALS levels, but not hepatic ALS mRNA. Streptozotocin
      diabetic rats, untreated or treated with human GH for 5 days, had significantly
      decreased serum ALS levels and liver ALS mRNA abundance. Insulin treatment
      normalized serum ALS without fully restoring ALS mRNA. Dexamethasone, an
      inhibitor of ALS synthesis by hepatocytes, significantly reduced both serum ALS
      and hepatic ALS mRNA. The discrepancies between hepatic expression and serum ALS
      levels in fasting and diabetes point to a complex regulatory mechanism in which
      events at the translational level or later may be as important as regulation of
      gene expression or mRNA stability.

PMID- 7527329
TI  - Roxithromycin. An update of its antimicrobial activity, pharmacokinetic
      properties and therapeutic use.
AB  - Roxithromycin is a derivative of the macrolide antibacterial erythromycin with in
      vitro antibacterial activity resembling that of the parent compound. The drug has
      activity against some Staphylococcus spp., many Streptococcus spp., Moraxella
      (Branhamella) catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila and
      Chlamydia trachomatis as well as many less common organisms. Measured using
      recently proposed guidelines, roxithromycin has in vitro activity against
      Haemophilus influenzae. In comparison with that of its parent compound, the
      pharmacokinetic profile of roxithromycin is characterised by high plasma, tissue
      and body fluid concentrations and a long half-life permitting an extended dosage
      interval. Roxithromycin has proven clinical efficacy in upper and lower
      respiratory infections, skin and soft tissue infections, urogenital infections
      and orodental infections, and appears to be as effective as more established
      treatments including erythromycin, amoxicillin/clavulanic acid and cefaclor. The
      drug has also shown promise in a variety of more specialised indications
      including opportunistic infections in human immunodeficiency virus (HIV)-positive
      patients and as part of a Helicobacter pylori eradication regimen. Roxithromycin
      is very well tolerated with an overall incidence of adverse events of
      approximately 4%. Thus, roxithromycin is an attractive therapeutic alternative in
      its established indications, especially when the option of once-daily
      administration is considered.

PMID- 7527333
TI  - Expression of insulin-like growth factors and their binding proteins in the
      estrogen responsive Ishikawa human endometrial cancer cell line.
AB  - In uterine tissue, estrogen regulates various components of the insulin-like
      growth factor system; however, there are few suitable in vitro systems to examine
      these effects. Here we have examined the effects of 17-beta estradiol (E2) on
      expression and synthesis of insulin-like growth factors (IGF-I and IGF-II) and
      the insulin-like growth factor binding proteins (IGFBPs) by Ishikawa human
      endometrial cancer cells. Using a semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR) assay, we demonstrated that both E2 and 4
      hydroxy-tamoxifen (OHT) enhanced IGF-I expression but had no effect on IGF-II
      expression. The pure antiestrogen ICI 182,780 had no effect on IGF-I expression
      and partially blocked the E2 and OHT effect on IGF-I expression. The effect of
      epidermal growth factor (EGF), which is able to mimic some of the effects of E2
      in Ishikawa cells and uterine tissue, was also examined. EGF, unlike E2, did not
      increase IGF-I expression but rather resulted in a significant decrease in IGF-I
      messenger RNA (mRNA) levels. EGF also resulted in a small, nonsignificant
      increase in IGF-II mRNA levels. IGFBP-3, -5, and -6 mRNAs were detected by
      Northern blot analyses of Ishikawa cells RNA. However, only IGFBP-3 was
      consistently detected by ligand blotting of conditioned medium. E2 had no
      significant effect on expression of any of the binding proteins, whereas EGF
      increased IGFBP-5 mRNA levels. These data provide the first in vitro
      demonstration of regulation of IGF-I expression by E2. The Ishikawa cell line may
      provide a useful model to further investigate the molecular mechanisms underlying
      E2 regulation of IGF-I expression. Furthermore, we have demonstrated a clear
      dissociation of the effects of E2 and EGF on IGF-I expression in this cell line.

PMID- 7527334
TI  - Expression and regulation of insulin-like growth factor-I (IGF-I) and IGF-binding
      protein messenger ribonucleic acid levels in tissues of hypophysectomized rats
      infused with IGF-I and growth hormone.
AB  - The expression and regulation of insulin-like growth factor-I (IGF-I) and IGF
      binding protein-2 (IGFBP-2), -3, -4, and -5 messages were studied in liver,
      kidney, spleen, thymus, heart, brain, skeletal muscle, testes, and epididymal
      (white) adipose tissue (WAT) from hypophysectomized rats infused with saline,
      recombinant human (rh) IGF-I, or rhGH and compared with tissue messenger RNA
      (mRNA) levels in age-matched normal rats. The IGF-I message was present in all of
      these tissues. It was most abundant in liver and WAT, but was barely detectable
      in kidney, brain, and thymus. GH dependence was most pronounced in liver,
      skeletal muscle, and WAT and less so in heart, testes, kidney, spleen, and
      thymus. The IGF-I message in brain was not influenced by hypophysectomy. IGF-I
      infusion induced a small increase in its own mRNA in skeletal muscle and WAT,
      whereas it decreased its own message in liver. IGFBPs were expressed in a tissue
      specific manner; IGFBP-2 mRNA was most abundant in testes and hypophysectomized
      liver, IGFBP-3 mRNA was most abundant in spleen, kidney, WAT, and liver, IGFBP-4
      mRNA was most abundant in liver, and IGFBP-5 mRNA was most abundant in kidney,
      WAT, and skeletal muscle. After hypophysectomy, significant decreases in IGFBP
      expression were observed in liver (except IGFBP-2), skeletal muscle, brain, WAT
      (except IGFBP-4), and testes (except IGFBP-2), in contrast to heart, kidney,
      spleen, and thymus. GH infusion did not affect IGFBP-2 mRNA levels in liver (in
      contrast to IGF-I infusion) or brain. Like GH, IGF-I normalized IGFBP-3 mRNA
      levels in liver, but, in contrast to GH, had no effect on IGFBP-5 mRNA in WAT. It
      was considerably less effective than GH in raising IGFBP-5 mRNA levels in
      skeletal muscle. Thus, GH infusion can exert different effects on IGF-I and IGFBP
      expression than infused rhIGF-I. Differences may be due to direct actions of GH
      at the tissue level, including auto/paracrine effects of locally produced IGF-I.

PMID- 7527326
TI  - Quinapril. A reappraisal of its pharmacology and therapeutic efficacy in
      cardiovascular disorders.
AB  - Following systemic absorption, quinapril is converted by de-esterification to
      quinaprilat (the active diacid metabolite), an inhibitor of angiotensin
      converting enzyme (ACE). Pharmacodynamic studies in animals indicate inhibition
      of ACE both in plasma and at tissue sites, such as the arterial wall and heart,
      following administration of quinapril. Tissue ACE inhibition may be an important
      component of the mechanism of action of quinapril (and other ACE inhibitors) in
      achieving favourable effects in cardiovascular disorders. Quinaprilat has a short
      elimination half-life (approximately 2 hours), but binds potently to and
      dissociates slowly from ACE, thus allowing once or twice daily administration of
      quinapril in the treatment of patients with hypertension or congestive heart
      failure. Quinapril 10 to 40 mg/day has achieved adequate control of blood
      pressure in most patients with essential hypertension in clinical trials. Some
      patients required quinapril dosages up to 80 mg/day and/or concomitant diuretic
      therapy. Titrating quinapril dosages from 10 to 40 mg/day increased response
      rates without increasing the incidence or severity of adverse events. Addition of
      hydrochlorothiazide to quinapril therapy improved response rates by approximately
      10 to 20% in patients with hypertension. In general, blood pressure control with
      quinapril monotherapy was similar to that achieved with enalapril or other
      standard antihypertensive agents in comparative trials. Quinapril < or = 40
      mg/day improved exercise tolerance, reduced the severity and frequency of
      symptoms, and improved functional (New York Heart Association) class in most
      clinical studies of patients with congestive heart failure. In addition,
      beneficial haemodynamic and echocardiographic changes achieved with quinapril
      were maintained for up to 1 year with continued administration to such patients,
      but its effect on survival in patients with congestive heart failure has not been
      reported. The tolerability profile of quinapril is broadly similar to that of
      other ACE inhibitors; pooled data from clinical trials indicated that 12% of
      patients with hypertension or congestive heart failure receiving quinapril
      experienced a treatment-related adverse effects compared with 15% of enalapril
      recipients and 16% of captopril recipients. Thus, quinapril has clearly
      established a role as an effective and well tolerated alternative to other ACE
      inhibitors for the treatment of hypertension and congestive heart failure. While
      effects of quinapril on survival of patients with congestive heart failure have
      not been determined, large intervention studies have demonstrated improved
      mortality rates with other ACE inhibitors. Further studies, including a large
      ongoing trial of normotensive patients with coronary artery disease but normal
      left ventricular function, may also establish a role for quinapril in treating
      patients with ischaemic heart disease.

PMID- 7527335
TI  - Proteolysis of insulin-like growth factor binding protein-3 during rat pregnancy:
      a role for matrix metalloproteinases.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is degraded by a cation
      dependent protease(s) present in the serum of late gestation rats. Proteolysis of
      IGFBP-3 results in an increase in IGF-I clearance and possibly in IGF
      bioavailability. Based on our previous findings that matrix metalloproteinases
      (MMPs) degrade IGFBP-3 in fibroblast conditioned media, we hypothesized that MMPs
      might be involved in the degradation of IGFBP-3 by rat pregnancy serum. In the
      present study, we demonstrate that tissue inhibitor of metalloproteinases (TIMP
      1), a specific inhibitor of all MMPs, inhibited significantly the degradation of
      125I-rhIGFBP-3 by both rat pregnancy serum and rat placental extracts. Purified
      human MMPs (principally MMP-1 and MMP-3) degraded IGFBP-3 in solution; MMP-3
      produced a pattern of IGFBP-3 degradation products identical in size to the
      fragments produced by pregnancy serum. Furthermore, the combined addition of
      antihuman MMP-1 IgG and anti-human MMP-3 IgG to rat pregnancy serum blocked
      almost completely the degradation of 125I-rhIGFBP-3, suggesting that these two
      MMPs are the principal MMPs involved in IGFBP-3 degradation in rat pregnancy
      serum. Together, these data suggest that MMPs function as IGFBP-3-degrading
      proteases in the serum of late gestational pregnant rats.

PMID- 7527336
TI  - Effects of nicotinamide and niacin on bleomycin-induced acute injury and
      subsequent fibrosis in hamster lungs.
AB  - Nicotinamide (500 or 250 mg/kg body wt) or niacin (100 or 50 mg/kg body wt) was
      administered to hamsters given an intratracheal injection of bleomycin (BLM). At
      7 days after the BLM injection, when compared with BLM-control animals, both
      nicotinamide- and niacin-treated animals showed similar acute lung injury,
      recognized as increases in the wet-to-dry lung weight ratio, intraalveolar
      albumin concentration, inflammatory cell number, and elastase activity. At 30
      days after the BLM injection, both nicotinamide and niacin attenuated the
      development of pulmonary fibrosis, as indicated by fewer fibrotic changes and a
      decreased amount of lung hydroxyproline. Histologic examination revealed that,
      compared with nicotinamide, niacin had more potent antifibrotic effects. Lung
      nicotinamide-adenine-dinucleotide (NAD) was less depleted in nicotinamide-treated
      animals than in BLM-control animals. Nicotinamide- and niacin-treated animals had
      more intraalveolar cells than the BLM-control animals. These findings suggest
      that the development of pulmonary fibrosis induced by BLM was prevented through
      maintaining NAD by the administration of nicotinamide or niacin. Since neither
      nicotinamide nor niacin attenuated the inflammatory response to acute lung
      injury, the amelioration of fibrosis by these treatments appears to be
      independent of the early events.

PMID- 7527337
TI  - Lung hyaluronan as assayed with a biotinylated hyaluronan-binding protein.
AB  - This study was designed to define how hyaluronan (HA) is bound in lung tissue.
      Aliquots of lyophilized hamster lungs were extracted with 0.5 M NaCl (associative
      conditions) or 4 M guanidine . HCL (Gu . HCl) (dissociative conditions) or with
      water. Aliquots were also digested with Pronase in phosphate-buffered saline
      (PBS) or in dilute Tris buffer. The nanogram amounts of solubilized HA were
      quantified by an inhibition assay based on the specificity of binding of HA to
      biotinylated HA-binding protein (B-HABP) rather than radioactive HA-binding
      protein. Lung HA was readily soluble. More than 80% of it was solubilized by one
      extraction with either 0.5 M NaCl or 4 M guanidine . HCl. Almost half of it was
      solubilized by two brief (15-min) water washes. After three extractions under
      associative conditions only 5% of the total HA remained insoluble and could exist
      in structural proteoglycan aggregates. However, HA is present in lung in more
      than one situation, as was discerned in Pronase digestion experiments. Digestion
      of lung tissue with Pronase solubilized total lung HA. In PBS all the HA was
      detected, but in dilute Tris buffer 52% of the HA solubilized was not available
      for combination with the B-HABP and was presumed to be bound to another lung
      component. Overall, the data suggest that lung HA is free to engage in water
      transport and to provide a protective coating for elastin and collagen fibers.

PMID- 7527338
TI  - The basement membrane at the equine hoof dermal epidermal junction.
AB  - In the equine hoof, the basement membrane connects the heavily keratinised hoof
      wall to the dense connective tissue of the distal phalanx, a region able to
      withstand considerable mechanical stress. This study investigated the properties
      of this important anatomical and physiological structure. In contrast to
      haematoxylin and eosin, the connective tissue stains, periodic acid Schiff,
      periodic acid silver methenamine and Azan showed good resolution of lamellar
      basement membrane. The lamellar basement membrane cross-reacted with mouse
      monoclonal antibodies raised against human laminin, thereby providing evidence
      that laminin is a component of the equine basement membrane. The ultrastructure
      of the equine hoof basement membrane was essentially the same as in other animals
      but appeared to have many anchoring fibrils and extensions of the lamina densa
      into the adjoining connective tissue, an arrangement interpreted to convey extra
      strength to the region. Large areas of the surface of the hoof wall basement
      membrane could be exposed to examination with the scanning electron microscope by
      treating tissue blocks with detergent/enzyme or sodium bromide. When epidermal
      lamellae were separated from their dermal counterparts the basement membrane
      stayed with the dermis and the dermal lamellae retained their natural shape
      despite the absence of an adjacent epidermis. The exposed surface of the lamellar
      basement membrane was generally smooth and unbroken, marked with small
      indentations and fine wrinkles. At the cut edges of the lamellae, a mesh of fine
      connective tissue fibres were attached to the inner surface of the basement
      membrane. The basement membrane of both toh coronary and terminal papillae was
      folded into numerous longitudinal ridges, all parallel to the long axis of the
      papillae.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527341
TI  - Properties of bacteriorhodopsin derivatives constructed by insertion of an
      exogenous epitope into extra-membrane loops.

PMID- 7527340
TI  - Preferential selection of adenosines for modification by double-stranded RNA
      adenosine deaminase.
AB  - Double-stranded RNA adenosine deaminase (dsRAD), previously called the double
      stranded RNA (dsRNA) unwinding/modifying activity, modifies adenosines to
      inosines within dsRNA. We used ribonuclease U2 and a mutant of ribonuclease T1 to
      map the sites of modification in several RNA duplexes. We found that dsRAD had a
      5' neighbor preference (A = U > C > G) but no apparent 3' neighbor preference.
      Further, the proximity of the strand termini affected whether an adenosine was
      modified. Most importantly, dsRAD exhibited selectivity, modifying a minimal
      number of adenosines in short dsRNAs. Our results suggest that the specific
      editing of glutamate receptor subunit B mRNA could be performed in vivo by dsRAD
      without the aid of specificity factors, and support the hypothesis that dsRAD is
      responsible for hypermutations in certain RNA viruses.

PMID- 7527342
TI  - Clinical experience with propafenone for cardiac arrhythmias in the young.
AB  - Seventy-two children were treated with propafenone between 1980 and 1990. The
      mean age was 34 months (range 0-192). Arrhythmias included atrioventricular re
      entry tachycardia in 32 patients (44%), atrial flutter in 16 (22%), atrial or
      junctional ectopic tachycardia in 10 (14%), atrial re-entry tachycardias in three
      (4%) and ventricular arrhythmias in 11 patients (16%). The efficacy of oral
      treatment was good in patients with atrio-ventricular re-entry tachycardia (80%),
      atrial flutter (71%) and atrial ectopic tachycardia (83%); it was poor in
      ventricular arrhythmias (40%). The mean oral dose was 13.5 mg.kg-1. day-1. Dosage
      and serum levels of propafenone did not differ whether the patients were treated
      successfully or not. No correlation between dosage and serum level was observed.
      Intravenous propafenone administration was only partially successful in
      suppressing supraventricular tachycardias (6 of 11 patients). The presence of a
      congenital heart defect and the time of onset of the arrhythmias had a
      significant influence on the efficacy of propafenone. Better results were
      observed in patients with normal hearts and in whom onset of arrhythmia was pre
      natal (success 80%) as well as in patients with arrhythmias seen early after
      surgery for congenital heart defects (success 87%). Success (65%) was also
      observed in patients without congenital heart defects and postnatal onset of
      supraventricular arrhythmias. Patients with ventricular or supraventricular
      arrhythmias late after corrective surgery showed the poorest response (31%).

PMID- 7527343
TI  - Pharmacological assessment of spantide II analogues.
AB  - We have studied the structure-activity relationship of a series of tachykinin
      receptor antagonists based on spantide II. Fifteen novel peptides were tested for
      their ability to antagonize the electrically evoked tachykinin receptor-mediated
      response in the isolated rabbit iris sphincter muscle. Substitution or deletion
      of one to three amino acids in the spantide II sequence caused significant
      changes in biological activity. Eight of the novel analogues were found to be as
      potent as or more potent than spantide II and some were found to have better
      water solubility. We tested the selectivity for different tachykinin receptors of
      spantide II and two of the eight most potent analogues. They all interacted with
      tachykinin NK1 (rabbit jugular vein) and tachykinin NK2 (rabbit pulmonary artery)
      receptors with pA2 values of about 6.5-7.5 at the NK1 receptor and of 5.9-7.2 at
      the NK2 receptor, while being inactive at the tachykinin NK3 receptor (rat portal
      vein). Spantide II and the novel analogues were without effect on electrically
      evoked cholinergic responses of the isolated rabbit iris sphincter and on
      electrically evoked sympathetic responses of the guinea-pig vas deferens;
      moreover, they were without local anaesthetic-like effects on action potentials
      of the frog sciatic nerve, which suggests that they do not produce a general
      neurosuppressive effect. They were as effective as or slightly less effective
      than spantide II in causing histamine release from rat peritoneal mast cells.

PMID- 7527339
TI  - Solution structure of human insulin-like growth factor II; recognition sites for
      receptors and binding proteins.
AB  - The three-dimensional structure of human insulin-like growth factor II was
      determined at high resolution in aqueous solution by NMR and simulated annealing
      based calculations. The structure is quite similar to those of insulin and
      insulin-like growth factor I, which consists of an alpha-helix followed by a turn
      and a strand in the B-region and two antiparallel alpha-helices in the A-region.
      However, the regions of Ala1-Glu6, Pro31-Arg40 and Thr62-Glu67 are not well
      defined for lack of distance constraints, possibly due to motional flexibility.
      Based on the resultant structure and the results of structure-activity
      relationships, we propose the interaction sites of insulin-like growth factor II
      with the type 2 insulin-like growth factor receptor and the insulin-like growth
      factor binding proteins. These sites partially overlap with each other at the
      opposite side of the putative binding surface to the insulin receptor and the
      type 1 insulin-like growth factor receptor. We also discuss the interaction modes
      of insulin-like growth factor II with the insulin receptor and the type 1 insulin
      like growth factor receptor.

PMID- 7527344
TI  - NG-Nitro-L-arginine protects against ischaemia-induced increases in nitric oxide
      and hippocampal neuro-degeneration in the gerbil.
AB  - To assess the effects of the nitric oxide synthase inhibitor NG-Nitro-L-arginine
      on behavioural, biochemical and histological changes following global ischaemia,
      the Mongolian gerbil was used. Ischaemia was induced by bilateral carotid
      occlusion for 5 min. NG-Nitro-L-arginine was administered i.p. at either 1 or 10
      mg/kg 30 min, 6, 24, and 48 h after surgery. 5 min bilateral carotid occluded
      animals were hyperactive 24, 48 and 72 h after surgery. NG-Nitro-L-arginine
      caused some attenuation in this hyperactivity. The activity of nitric oxide
      synthase was increased in the cerebellum, brain stem, striatum, cerebral cortex
      and hippocampus of 5 min bilateral carotid occluded animals. NG-Nitro-L-arginine
      reversed the increase in nitric oxide synthase activity in all brain regions.
      Extensive neuronal death was observed in the CA1 layer of the hippocampus in 5
      min bilateral carotid occluded animals 96 h after surgery. NG-Nitro-L-arginine
      significantly protected against the neuronal death of cells in the CA1 layer.

PMID- 7527345
TI  - Galantide stimulates sexual behaviour in male rats.
AB  - While intracerebroventricular injection of galanin (5 micrograms/rat) inhibited
      sexual behavior in experienced male rats--without producing any other locomotor
      or behavioral deficit-, injection of the galanin antagonist, galantide, by the
      same route (1 or 2 micrograms/rat) stimulated sexual behavior (improving arousal,
      motivation and performance indexes) and antagonized the effect of galanin. These
      data further suggest that galanin plays a physiological role in male sexual
      behavior.

PMID- 7527348
TI  - Rapid kinetics of G protein subunit association: a rate-limiting conformational
      change?
AB  - G protein subunit association and dissociation are thought to play an important
      role in signal transduction. We measured alpha beta gamma heterocomplex formation
      using resonance energy transfer. Fluorescein-labelled alpha(F-alpha) emission was
      quenched approximately 10% on mixing with eosin-labelled beta gamma(E-beta
      gamma). Unlabelled beta gamma did not quench F-alpha fluorescence. Stopped-flow
      kinetics showed a t1/2 ranging from 2.5 s to 0.25 s for 50 nM to 1200 nM E-beta
      gamma. The rate saturated at high E-beta gamma concentrations consistent with a
      two-step mechanism. We report the first rapid-mix studies of G protein subunit
      association kinetics which suggest that alpha and beta gamma combine by a two
      step process with a maximal rate of 4.1 +/- 0.4 s-1.

PMID- 7527349
TI  - Spectroscopic evidence for an intramolecular RNA triple helix.
AB  - A 29-base RNA oligomer has been chemically synthesized and shown to form an
      intramolecular triple helix in solution at acidic pH. Assignment of the majority
      of the exchangeable proton NMR resonances demonstrated the Watson-Crick and
      Hoogsteen base pairings consistent with folding to form pyrimidine-purine
      pyrimidine base triplets. FTIR spectroscopy provided independent evidence of base
      triplet formation, and indicated a predominately C3'-endo sugar pucker. UV
      absorption as a function of temperature suggested monophasic melting behaviour,
      which was confirmed by NMR of the imino protons.

PMID- 7527347
TI  - A new biological activity for the neuropeptide FMRFamide: experimental evidence
      for a secretagogue effect on amylase secretion in the scallop Pecten maximus.
AB  - FMRFamide immunoreactivity in the digestive tract of the bivalve mollusc Pecten
      maximus was investigated by immunocytochemistry. Positive FMRFamide-like
      immunoreactivity was detected in nerve fibres in close contact with exocrine
      alpha amylase secreting cells. Physiological studies on enzymatically dissociated
      cells of the stomach-digestive gland complex demonstrated the involvement of
      FMRFamide and analogues in the control of alpha amylase release from the cells.
      The FMRFamide-induced secretion was shown to be time- and dose-dependent. In
      contrast to most naturally occurring vertebrate secretagogues which are hormones,
      FMRFamide appears to work in our in vitro system as a paracrine factor.

PMID- 7527346
TI  - Hsp70: a carrier molecule with built-in adjuvanticity.
AB  - One problem associated with the development of subunit vaccines is their limited
      immunogenicity, due to their physico-chemical structure, their inability to
      encounter the correct MHC restriction element, or the need for strong adjuvants
      to be delivered along with them. These problems are usually solved by conjugating
      target epitopes (peptides or oligosaccharides) with carrier proteins which
      provide a source of T-cell epitopes recognised by a large proportion of the
      vaccinated individuals. We have shown that mycobacterial hsp65 and hsp70 exert a
      strong helper effect in vivo when conjugated to synthetic peptides or
      oligosaccharides. Interestingly, this helper effect did not require the need for
      any adjuvant, either in mice or in monkeys. The helper effect mediated by the
      hsp65 required that animals were previously primed with either live BCG or the
      hsp65 alone; on the other hand, such a priming was not required when the hsp70
      was used in the conjugates. Similar results were obtained with HSP molecules from
      Escherichia coli. This may suggest that the adjuvant-free helper effect observed
      applies not only to mycobacterial HSP, but also to HSP from other prokaryotes.
      These findings suggest that microbial hsp70 could be considered for the design of
      conjugated vaccine constructs for eventual human use.

PMID- 7527350
TI  - Possible involvement of adenylylation in the modification of a 26 kDa protein in
      rat parotid acinar cells.
AB  - 1. Adenylylation, a posttranslational modification of proteins, was investigated
      in saponin-permeabilized acinar cells of the rat parotid gland. 2. When cells
      were incubated with [2,8-3H]ATP, several proteins, including a 26 kDa protein in
      the particulate fraction, were labeled. 3. Upon incubation of cells with [alpha
      32P]ATP in the presence of cAMP and 3-isobutyl-1-methylxanthine, 32P-labeling of
      the 26 kDa protein was observed. 4. After treatment with snake venom
      phosphodiesterase, [32P]AMP was released from the 26 kDa protein. Such release
      was not observed when cells were labeled with [gamma-32P]ATP. 5. The 32P-labeling
      pattern of proteins with [alpha-32P]ATP was clearly different from that with
      [adenylate-32P]NAD+. 6. The results suggest that the 26 kDa protein is one of the
      adenylylation substrates in rat parotid acinar cells.

PMID- 7527351
TI  - Development of cytochrome P-450 side chain cleavage mRNA levels in neonatal
      ovaries of normal and hypogonadal (hpg) mice.
AB  - Cytochrome P-450 side chain cleavage (P-450scc) is vital for biosynthesis of
      gonadal steroids. In this study changes in P-450scc mRNA levels and cholesterol
      side-chain cleavage (CSCC) enzyme activity have been measured during development
      in the ovary of the normal mouse and the hypogonadal (hpg) mouse which lacks
      circulating gonadotrophins. Levels of P-450scc mRNA were measured using a semi
      quantitative reverse transcription-polymerase chain reaction technique for which
      part of the 5' sequence of a mouse P-450scc cDNA was sequenced. On the day of
      birth P-450scc mRNA was present at low levels in the mouse ovary. Thereafter
      there was no change in P-450scc mRNA levels for 5 days after which time levels
      increased significantly to reach a peak around day 10. Activity of CSCC showed a
      similar pattern of development although activity was not detectable on days 1 and
      3. In the hpg mouse P-450scc mRNA levels were normal on day 1 but did not
      increase thereafter up to 15 days. These results show that there is gonadotrophin
      independent expression of P-450scc mRNA in the mouse ovary at birth when only
      primordial follicles and stromal tissue are present. As the ovary develops after
      5 days changes in P-450scc mRNA levels become gonadotrophin-dependent and
      coincide with maturation of secondary follicles.

PMID- 7527353
TI  - Basic fibroblast growth factor (bFGF) and two of its receptors, FGFR1 and FGFR2:
      gene expression in the rat brain during postnatal development as determined by
      quantitative RT-PCR.
AB  - Regional and temporal patterns of the expression of basic fibroblast growth
      factor (bFGF), and two of its high affinity receptors (FGFR1 and FGFR2), were
      examined in the male rat brain during early postnatal development; the reverse
      transcription-polymerase chain reaction (RT-PCR) was used to obtain mRNA
      measurements which were expressed relative to mRNA for GAPDH as a constant. In
      the rat cerebrum, the mRNAs for bFGF and for FGFR2 were relatively low in amount
      within the first postnatal week, but by 28 days, they were as high as in the 1
      year-old rat cerebrum. In contrast, the expression of FGFR1 was biphasic: mRNA
      levels were higher at postnatal days 1 and 28 than at day 21. Quantitation of
      mRNA from microdissected regions of 28-day-old rat brain revealed that the
      expression of bFGF and of FGFR2 showed a marked variation between regions but the
      expression of FGFR1 appeared less variable between the regions that were
      analyzed. For all three genes the hippocampus appeared to have high relative
      amounts of mRNA. The temporal patterns of expression of bFGF, FGFR1 and FGFR2
      also differed with brain region during early postnatal development. In the
      occipital cortex and inferior colliculus, the mRNAs for bFGF and FGFR2 both
      increased in amount during the first month, unlike that for FGFR1. However, in
      the cerebellum, the highest expression of bFGF and FGFR1 mRNAs occurred at
      postnatal day 1; FGFR2 expression apparently showed less change with age. The
      temporal changes in bFGF, FGFR1 and FGFR2 expression in different brain regions
      during early postnatal development suggest that receptor regulation may permit
      different physiological effects of bFGF according to brain region and
      developmental age.

PMID- 7527352
TI  - Androgen regulation of the messenger RNA encoding diazepam-binding inhibitor/acyl
      CoA-binding protein in the human prostatic adenocarcinoma cell line LNCaP.
AB  - To study the mechanisms by which androgens intervene in the regulation of growth
      and differentiation of human prostatic epithelial cells, cDNA clones encoding
      putative prostate-secreted proteins were characterized and tested as potential
      markers for androgen action. One of the isolated cDNAs expressed diazepam-binding
      inhibitor/acyl-CoA-binding protein (DBI/ACBP), suggesting that this polypeptide,
      that has been implicated in a large number of biochemical processes, is expressed
      and secreted by prostate cells. As demonstrated by Northern blot analysis, the
      mRNA encoding DBI/ACBP was expressed in prostate tissue and in the three human
      prostatic adenocarcinoma cell lines tested: LNCaP, PC-3 and DU-145. In androgen
      sensitive LNCaP cells, the synthetic androgen R1881 stimulated the DBI/ACBP
      steady state mRNA levels with half maximal effects at a concentration of 0.2 nM.
      Increases were a maximal 12 h after addition of the synthetic hormone. DBI/ACBP
      mRNA levels could also be stimulated by the synthetic androgen mibolerone and by
      the natural androgens testosterone and dihydrotestosterone. In agreement with the
      altered steroid specificity of the androgen receptor in LNCaP cells, estradiol
      and progesterone also exerted a stimulatory effect. Cortisol and the synthetic
      glucocorticoid dexamethasone were without effect. Androgen stimulation of
      DBI/ACBP mRNA levels was abolished in the presence of the protein synthesis
      inhibitor cycloheximide, implying a role for labile or androgen-induced proteins
      in this androgen stimulation. This is in contrast to the androgen stimulation of
      the mRNA encoding prostate-specific antigen (PSA), suggesting that different
      mechanisms are involved in the androgen regulation of these two genes. Although
      further experiments are required to confirm that DBI/ACBP is secreted by
      prostatic epithelial cells, these data demonstrate that the mRNA encoding
      DBI/ACBP is expressed in prostate cells and is affected by androgens in androgen
      responsive LNCaP cells.

PMID- 7527354
TI  - Differential effects of topical retinoic acid application on keratin K1 and
      filaggrin expression in mouse epidermis.
AB  - Retinoic acid (RA) modulates epidermal homeostasis and affects differentiation
      associated proteins such as keratin K1 and filaggrin. Because results from in
      vitro and in vivo studies have been conflicting with respect to RA effects on
      keratinization, we examined the terminal differentiation of epidermal cell
      cohorts after RA stimulation in vivo. Pulse-labelling with 5-bromo-2-deoxyuridine
      (BrdU) was performed by intraperitoneal injection of mice immediately or at 16 h
      after a single topical application of 100 nmol RA. The cell cohort labelled at
      the time of RA application consisted of previously unperturbed cells exposed to
      RA after initiation of S-phase, whereas the cohort labelled 16 h after RA
      application consisted of cells stimulated into the S-phase by RA. These two
      cohorts of partially synchronized cells were followed for up to 72 h after BrdU
      labelling. Such labelling combined with keratin K1 or filaggrin expression was
      scored by paired immunofluorescence staining of skin sections. The onset of
      keratin K1 expression was unchanged in both series after RA treatment, while
      filaggrin appeared earlier than in controls. The differential effect of RA on the
      maturation markers was related to the proliferative activity, the increased cell
      turnover, and the shortened epidermal transit time. The onset of keratin
      expression appeared to be regulated before the postmitotic period, whereas
      filaggrin expression appeared to be regulated during the late phase of the
      maturation process, thus being influenced by the actual epidermal kinetics and
      structural alterations. These results suggested that the effect of RA on
      epidermal differentiation is secondary to its effect on proliferation, as
      determined by the altered cellular age distribution following regenerative
      proliferation.

PMID- 7527355
TI  - Application of cantharidin or 12-O-tetradecanoylphorbol-13-acetate on mouse
      epidermis induces a cell population shift that causes altered keratin
      distribution.
AB  - The tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) causes changes in
      epidermal protein expression, especially in the major differentiation products
      keratins K1 and K10. These keratins and filaggrin were studied in a pulse
      labelled cell cohort in hairless mouse epidermis stimulated to proliferate by TPA
      or the hyperplasiogen cantharidin. Cells in DNA synthesis were pulse-labelled by
      5-bromo-2-deoxyuridine (BrdU) 16 h after topical application of cantharidin or
      TPA. The BrdU-labelled cell cohort, the two keratins, and filaggrin were
      spatially mapped by paired immunofluorescence staining. Both cantharidin- and TPA
      treated epidermis displayed altered distributions of K1 and K10 with expression
      only in the outermost cell layers, but the start of their postreplicative
      expression paralleled that in normal epidermis (18 h for K1 and 24 h for K10
      after the last round of DNA synthesis). Cantharidin- and TPA-induced epidermal
      hyperplasia showed increased basal cell proliferation, accelerated suprabasal
      migration, and shortened transit time. Thus, the newly formed hyperplastic
      epidermis was composed of keratinocytes with a lower mean cellular age than that
      seen in unperturbed epidermis, which caused altered distribution of K1 and K10.
      Both hyperplastic and normal epidermis showed filaggrin expression in stratum
      granulosum; this started earlier in treated (30-36 h) than in untreated (96 h)
      skin. We concluded that the postmitotic onset of K1 and K10 expression was
      unaltered in regenerative epidermis, whereas filaggrin expression was
      considerably accelerated and thus influenced by the cell kinetic changes.

PMID- 7527356
TI  - Cytokeratin-positive and cytokeratin-negative cultured endothelial cells from
      bovine aorta and vena cava.
AB  - The heterogeneous morphology of microvascular endothelial cells obtained from the
      bovine corpus luteum was recently attributed to the occurrence of cytokeratin
      (CK) positive and CK negative endothelial cells. The aim of the present study was
      to establish comparable differences for bovine macrovascular endothelial cells.
      For this reason, endothelial cells were scraped from the abdominal aorta as well
      as the inferior vena cava of cows. At the level of phase contrast microscopy,
      primary cultures originating from both large vessels could be classified as CK
      positive or CK negative endothelial cells. After seeding CK positive endothelial
      cells on Matrigel matrix, a two-dimensional meshwork of so called pseudotubules
      formed within 2 h. By using immunofluorescence localization CK positive cells
      were identified by a complex meshwork. It consisted of CK 8, 18 and 19 as
      displayed by Western blots. The CK negative group showed spindle-shaped or
      polygonal endothelial cells according to light microscopy. In postconfluent
      cultures, spindle-shaped cells developed a three-dimensional meshwork of tubules.
      After seeding spindle-shaped cells on Vitrogen 100 matrix, pseudotubules formed
      within 1 day. In considering the frequency of occurrence, primary harvests from
      the vena cava contained less than 1% CK positive cells. With respect to growth,
      the cell number was two to three times higher for the CK negative group than the
      CK positive group as judged on day 13 after cell seeding. It is concluded that
      subpopulations of endothelial cells are derived from large blood vessels.

PMID- 7527358
TI  - Expandable esophageal stents: initial experience with a new nitinol stent.

PMID- 7527359
TI  - Polyurethane-covered mesh stent for malignant esophageal stenosis with fistulas.

PMID- 7527357
TI  - Emergency endoscopy: recanalization of intestinal obstruction caused by
      colorectal cancer.
AB  - Endoscopic recanalization was attempted in 17 patients with obstruction caused by
      colorectal cancer who were at high surgical risk on account of their poor
      clinical condition. Combined use was made of pneumatic and mechanical dilation,
      debulking with a diathermal snare, and photoablation with neodymium-yttrium
      aluminum-garnet laser. Successful recanalization was obtained in 94% of cases.
      The only failure was in a patient with a neoplasm of the rectosigmoid junction.
      Elective surgery was not performed on the patients after recanalization because
      of the presence of severe concomitant disease or diffuse metastasis. Patients
      were followed for 6.25 +/- 6.17 months with 1.6 +/- 0.7 treatments within the
      first month to stabilize patency and then with an average of 0.88 +/- 0.63
      treatments per month to maintain patency. Only 2 patients had recurrence of
      obstruction, and the actuarial survival was 63% at 6 months and 23% at 1 year.
      Endoscopic treatment has proved effective because it allows rapid recanalization
      with resolution of emergency and maintenance of patency in patients for whom
      elective surgery is not indicated. In selected cases, therefore, endoscopic
      recanalization is a sound alternative to emergency surgery.

PMID- 7527360
TI  - Repositioning of an esophageal stent after migration using a snare.

PMID- 7527361
TI  - Isolation and partial purification of a carbapenem-hydrolysing metallo-beta
      lactamase from Pseudomonas cepacia.
AB  - A metallo-beta-lactamase has been isolated from a clinical strain of Pseudomonas
      cepacia and partially purified using Cibacron blue F3GA coupled agarose. The
      resulting preparation showed a single band of beta-lactamase activity (pI 8.45)
      after analytical isoelectric focusing. The enzyme was particularly effective in
      the hydrolysis of imipenem. Meropenem, biapenem, cephaloridine, ceftazidime,
      benzylpenicillin, ampicillin and carbenicillin were also hydrolysed, although at
      a lower rate. An unusual inhibition profile was noted. Inhibition by the metal
      ion chelators ethylenediaminetetraacetic acid and o-phenanthroline was reversed
      by addition of zinc, indicating a metallo-enzyme, whilst > 90% inhibition was
      attainable with 0.1 mM concentrations of tazobactam and clavulanic acid. A study
      of 8 other clinical isolates showed the enzyme to be present and inducible by
      imipenem in each case. This enzyme was assigned PCM-I (Pseudomonas cepacia
      metalloenzyme I).

PMID- 7527363
TI  - 16S rDNA sequence and phylogenetic position of an uncultivated spirochete from
      the hindgut of the termite Mastotermes darwiniensis Froggatt.
AB  - We have analyzed the 16S rDNA sequence and the phylogenetic position of an
      uncultivated spirochete from the hindgut contents of the Australian termite
      Mastotermes darwiniensis Froggatt. The 16S rRNA genes of bacteria from the
      hindgut contents of Mastotermes darwiniensis were amplified by polymerase chain
      reaction. The amplification products were cloned and sequenced. The sequences
      were compared to known homologous primary structures. Two of the clones (MDS1 and
      MDS3) had an insert of 1498 nucleotides showing typical signatures of spirochete
      16S rRNA sequences. The sequences of the two clones were most similar to the 16S
      rRNA sequence of Spirochaeta stenostrepta (89.8%) and Treponema sp. strain H1
      (90.7%). Phylogenetical analysis positioned the hindgut spirochete sequence with
      that of the free-living anaerobic Spirochaeta stenostrepta and Treponema sp.
      strain H1 as its nearest relatives within the cluster of the spirochetes. We
      conclude that analyzed SSU rDNA sequences originate from a spirochete related to
      the genus Treponema. It is possibly one of the uncultivated unique spirochetes
      symbiotic in termite hindguts.

PMID- 7527364
TI  - Monoclonal antibodies against Vibrio anguillarum O2 and Vibrio ordalii identify
      antigenic differences in lipopolysaccharide O-antigens.
AB  - Monoclonal antibodies (mAbs) that recognize distinct species-specific antigenic
      epitopes in O-antigens from Vibrio anguillarum O2, O2a and certain O2b strains
      (mAb 7B4) and from Vibrio ordalii strains (mAbs A16 and 7D11) were generated.
      Western immunoblot analysis using these mAbs revealed that vibrio strains grown
      in the presence of fresh rainbow trout blood expressed lipopolysaccharide (LPS)
      with longer (high molecular mass) O-antigens and extracellular capsular layers
      when compared to strains grown without rainbow trout blood. We also generated
      mAbs that react with O-antigens from V. anguillarum serotype O1 (mAbs 7B8, 7B5
      and 1C3) and serotype O3 (mAbs 13A1 and 14C5) strains. These mAbs provide rapid
      and accurate diagnostic reagents for serological differentiation of V. ordalii
      from serotype O2 strains of V. anguillarum, and for serotyping of these
      pathogenic vibrios.

PMID- 7527362
TI  - Purification and characterization of P fimbriae from an Escherichia coli strain
      isolated from a septicemic turkey.
AB  - A pap+ Escherichia coli isolate from a turkey with colisepticemia expressed P
      fimbriae with a major subunit of an apparent molecular mass of 18 kDa which
      reacted with anti-F11 serum. This fimbriae was purified and polyclonal antiserum
      was produced in rabbits. The N-terminal amino acid sequence of the major fimbrial
      subunit of the avian P fimbriae was identical to that of F11. On immunoblotting,
      the antiserum against the avian P fimbriae strongly reacted with the major
      subunit of the homologous fimbriae, with F11, and with F165(1) fimbriae. Some
      antigenic determinants on the major subunits of F13, F7(1), and F7(2) fimbriae,
      with a stronger reaction against F13 fimbriae, were also recognized. The F11
      antiserum reacted similarly to the antiserum against avian P fimbriae although
      cross-reactions against F13, F7(1), and F7(2) fimbriae were equivalent. In a
      competitive enzyme-linked immunosorbent assay, serological differences were
      observed between the purified avian P fimbriae and F11. Thus, the avian P
      fimbriae is closely related but not identical to F11 fimbriae which are
      associated with E. coli isolated from human urinary tract infection.

PMID- 7527365
TI  - Isolation and characterization of the flagellar hook of Campylobacter jejuni.
AB  - A method for purification of the flagellar hook of Campylobacter jejuni is
      described. The hook was shown to be composed of a subunit protein, which has a
      molecular mass of 92,000 and an isoelectric point of pI 4.8. A monoclonal
      antibody and a polyvalent antiserum was raised against the purified flagellar
      hook of C. jejuni. Immuno-electronmicroscopy revealed that the epitope recognized
      by the monoclonal antibody is surface-located. However, this antibody reacted
      only with the hook of the immunization strain, but not with other strains or
      other flagellated bacteria. Thus, our data indicate that the immunodominant
      epitopes are located on the surface of the hook and that these epitopes are
      strain-specific.

PMID- 7527366
TI  - Standardization of immunoassays for antiphospholipid antibodies with beta 2GPI
      and role of other phospholipid cofactors.
AB  - Presence of beta 2 Glycoprotein I (beta 2GPI), in addition to phospholipids, is
      an absolute requirement for binding APA. This binding is frequently observed with
      beta 2GPI coated alone, however many APA react only with beta 2GPI complexed to
      phospholipids, but not with phospholipids alone. We demonstrate that a subgroup
      of rabbit polyclonal antibodies to human beta 2GPI binds to this protein only
      when it is coated on a solid surface, but not if it is in solution. In addition,
      beta 2GPI present in goat serum is strongly fixed by the coated phospholipids and
      the complexes formed bind as well APA as the rabbit antibodies to beta 2GPI. The
      diluent used for testing APA, has a strong incidence on APA's reactivity as it
      can be a source of beta 2GPI. Antibody binding to beta 2GPI, Prothrombin, Protein
      S, and Annexin V, coated in the presence or in the absence of phospholipids, was
      tested in 55 patients with the antiphospholipid syndrome. The strongest binding
      of antibodies was observed in 39 plasma to a mixture of phospholipids and
      purified human beta 2GPI, however 17 samples also presented a significant
      reactivity to beta 2GPI alone. Nine plasmas contained antibodies to Prothrombin,
      4 to Protein S, 3 to Annexin V, and 1 to Protein C. We conclude that most of the
      APA are directed to a complex of beta 2GPI and phospholipids although in some
      patients antibodies to beta 2GPI alone or to other phospholipid binding proteins
      are present.

PMID- 7527369
TI  - Risperidone's cost.

PMID- 7527368
TI  - Time-dependent changes in platelet aggregation, fibrinolytic activity, and
      peripheral serotonergic measures in rats subjected to water immersion restraint
      stress.
AB  - The effects of water immersion restraint stress on collagen-induced platelet
      aggregation in whole blood, and on the fibrinolytic and serotonergic systems in
      rats have been studied. One hour long stress caused a release of tissue
      plasminogen activator (tPA) into the blood and a shortening of euglobulin clot
      lysis time (ECLT), whereas restraint of longer duration was responsible for a
      reduction in platelet aggregation, an elevation in the activity of plasminogen
      activator inhibitor with a concomitant fall in tPA and a prolongation of ECLT
      relative to controls. Whole-blood and plasma serotonin and its metabolite 5
      hydroxyindoleacetic acid were also higher in the stressed rats and whole-blood
      serotonin level showed a negative correlation with tPA in the stressed rats.
      Either stress and/or its duration are responsible for changes in both
      fibrinolytic and serotonergic systems.

PMID- 7527367
TI  - Single-donor platelet concentrates: changes of surface glycoproteins during
      storage.
AB  - Storage of single-donor platelet concentrates is currently limited to 5 days.
      During this period, however, numerous morphologic and biochemical changes have
      been observed. These changes result in functional impairment of stored platelets.
      The present study describes increased binding of a monoclonal antibody against
      GMP 140 on the surface of stored single-donor platelets revealing an activation
      process. In contrast, binding of monoclonal antibodies directed against
      glycoprotein complex (GP) IIb-IIIa and ligand-induced binding site (LIBS1) is
      slightly diminished during storage. When platelets are stimulated with ADP GMP
      140, GP IIb-IIIa, and LIBS1 are expressed to a higher extent than on the surface
      on nonstimulated platelets. The quantity exposed, however, depends upon the
      storage time. It is significantly reduced when platelets are stored for longer
      than 1-2 days. The present data indicate that storage of single-donor platelet
      concentrates affects fibrinogen binding, cell to cell cohesion, and release
      reaction. The results are in good agreement with conventional aggregation and in
      vitro bleeding time measurements.

PMID- 7527370
TI  - Complete detection of mutations in cystic fibrosis patients of Native American
      origin.
AB  - An increased incidence of cystic fibrosis (CF) has been reported in some
      populations of Native Americans of the Southwest such as the Pueblo, which is a
      genetic isolate. As the most common mutation found in Caucasians (delta F508) was
      absent and only one chromosome carried the G542X mutation, we decided to analyze
      the entire coding sequence of the CFTR gene in eight Pueblo CF patients. We have
      identified four different mutations: G542X, R1162X, 3849+10kbC-->T, and D648V
      that account for these 16 haplotypes. The R1162X was found on 11 chromosomes.
      Using intragenic microsatellites, we have compared the haplotypes of those
      chromosomes to those of Italian origin where the R1162X mutation was initially
      reported. These haplotypes turned out to be identical, suggesting a common origin
      and an admixture with Italian or Spanish settlers, followed by typical founder
      effect. In contrast the 3849+10kbC-->T mutation, which was found on three
      chromosomes, is associated with different haplotypes than those on chromosomes
      carrying the same mutation in Caucasians. A novel mutation, D648V, observed on
      one chromosome has not been found outside the Pueblo population.

PMID- 7527372
TI  - A WAGR region gene between PAX-6 and FSHB expressed in fetal brain.
AB  - Developmental delay or mental retardation is a frequent component of multi-system
      anomaly syndromes associated with chromosomal deletions. Isolation of genes
      involved in the mental dysfunction in these disorders should define loci
      important in brain formation or function. We have identified a highly conserved
      locus in the distal part of 11p13 that is prominently expressed in fetal brain.
      Minimal expression is observed in a number of other fetal tissues. The gene maps
      distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor
      (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a
      region previously implicated in the mental retardation component of some WAGR
      syndrome patients. Within fetal brain, the corresponding transcript is prominent
      in frontal, motor and primary visual cortex as well as in the caudate-putamen.
      The characteristics of this gene, including the striking evolutionary
      conservation at the locus, suggest that the encoded protein may function in brain
      development.

PMID- 7527371
TI  - Rapid screening of myelin genes in CMT1 patients by SSCP analysis: identification
      of new mutations and polymorphisms in the P0 gene.
AB  - Charcot-Marie-Tooth type 1 (CMT1) disease or hereditary motor and sensory
      neuropathy type I (HMSNI) is an autosomal dominant peripheral neuropathy. In most
      CMT1 families, the disease cosegregates with a 1.5-Mb duplication on chromosome
      17p11.2 (CMT1A). A few patients have been found with mutations in the peripheral
      myelin protein 22 (PMP-22) gene located in the CMT1A region. In other families
      mutations have been identified in the major peripheral myelin protein P0 gene
      localized on chromosome 1q21-q23 (CMT1B). We performed a rapid mutation screening
      of the PMP-22 and P0 genes in non-duplicated CMT1 patients by single-strand
      conformation polymorphism analysis followed by direct polymerase chain reaction
      sequencing of genomic DNA. Six new single base changes in the P0 gene were
      observed: two missense mutations in, respectively, exons 2 and 3, two nonsense
      mutations in exon 4, and two silent mutations or polymorphisms in, respectively,
      exons 3 and 6.

PMID- 7527374
TI  - Therapy for hepatitis B virus infection.
AB  - Major advances have been made in the therapy of chronic viral hepatitis B during
      the past several years. This period has witnessed the publication of large,
      multicenter trials of recombinant interferon alfa for chronic hepatitis B in the
      United States and the completion of several similarly designed studies in North
      America, Europe and Asia. These studies have defined an initial response rate of
      approximately 40% to 50%. In contrast to the experience with chronic hepatitis C,
      loss of viral replication is generally sustained. Repeat courses of therapy are
      likely to result in the same type of response as that observed initially.
      Quantitative assessment of viral replication (HBV DNA, HBeAg) is important in
      predicting the likelihood of response and in monitoring patients during therapy.
      Perhaps the most compelling reason to treat chronic hepatitis B with interferon
      is the disappearance of circulating HBsAg in one third of responders with a
      further increase in frequency of this phenomenon as follow-up continues. Another
      important advantage to treatment is the striking degree of histologic improvement
      that is frequently observed years after a response has been achieved. Although a
      substantial number of patients do not respond to interferon, several promising
      agents that should allow for a greater degree of success, when used either alone
      or in combination with interferon, are under study. A short course of
      corticosteroids prior to interferon appears to improve response rates in patients
      who have low ALT levels at baseline and has been the preferred approach for these
      patients at our medical center. Progress is being made in the development of
      safer interferon regimens for patients with mild-to-moderate hepatic
      decompensation. Nonetheless, even patients with marginal synthetic function, as
      reflected by albumin levels within the low-normal range, appear to be at greater
      risk for complications during therapy and should preferably be referred for
      inclusion in research programs. Appropriate patient selection remains a critical
      step for maximizing the safety as well as efficacy of interferon treatment.

PMID- 7527376
TI  - A secreted mucin carrying sialyl-Lewis a from colon carcinoma cells binds to E
      selectin and inhibits HL-60 cell adhesion.
AB  - Sialyl-Lewis x and a are known as ligands for E-selectin (ELAM-I) involved in
      leukocyte-endothelial adhesion. L-CanAg (light cancer antigen), secreted by a
      colon carcinoma cell line COLO 205, is a soluble mucin-type glycoprotein
      expressing sialyl-Lewis a antigens. L-CanAg was purified from spent culture
      medium by trichloracetic acid precipitation and Superose 6 gel filtration. With a
      monoclonal antibody against E-selectin (BBAI) as a positive control, the purified
      L-CanAg was shown to bind to E-selectin-Fc coated into plastic microtiter wells
      and to the surface of transiently E-selectin-transfected COS-I cells in a Ca(2+)
      dependent way. Immunofluorescent double labelling showed that both BBAI and L
      CanAg stained the same cells and morphological co-localization on E-selectin
      transfected COS-I cells. Like BBAI, L-CanAg can inhibit leukocyte HL-60 cell
      adhesion to E-selectin-transfected COS-I cells, and this inhibition can be
      blocked by a F(ab')2 fragment directed against the sialyl-Lewis a epitope.

PMID- 7527375
TI  - Therapy for chronic hepatitis C.
AB  - Hepatitis C is the silent epidemic of the 1970s and 1980s. Interferon alfa is
      currently the only effective treatment. Enthusiasm for interferon therapy must be
      tempered because advanced disease usually requires years or even decades to
      develop and does not occur in all patients. Few patients with chronic hepatitis C
      derive long-term improvement from a single 6-month course of interferon therapy.
      Most initial responders relapse and require long-term interferon treatment to
      suppress the virus. Obviously, the initial goals and expectations for interferon
      therapy require rethinking. Therapy should not be undertaken by physician or
      patient with the idea that therapy will be limited to 6 months. The most
      appropriate goal of therapy now appears to be the long-term control of the
      biochemical, virologic, and histologic activity of the disease. Unfortunately,
      the most effective therapeutic regimen for achieving this goal is not yet known
      and will require continued clinical research.

PMID- 7527373
TI  - Autoimmune hepatitis and viral infection.
AB  - In summary, type 1 autoimmune hepatitis is infrequently associated with serologic
      markers of viral infection, and there is no direct evidence that viruses are
      important causes of this disease. Patients seropositive for anti-LKM1 are
      commonly infected with HCV, but these patients have predominant features of
      chronic viral hepatitis and frequently lack antibodies to P450IID6. Such patients
      respond to therapy with interferon and should be distinguished from patients with
      type 2 autoimmune hepatitis who have anti-P450IID6, seronegativity for anti-HCV,
      and responsiveness to corticosteroids. In patients with ANA and/or SMA
      seropositivity and anti-HCV, a false-positive reaction for anti-HCV must be
      excluded by recombinant immunoblot assay. Patients with false anti-HCV
      seropositivity should be treated with corticosteroids. In contrast, patients with
      a true viral infection and low-titer autoantibodies should be treated with
      interferon. In patients with true viral infection and high titers of auto
      antibodies, the treatment decision must balance the autoimmune and viral
      manifestations. An empiric trial of corticosteroids is justified if autoimmune
      features predominate.

PMID- 7527377
TI  - In vivo anti-influenza virus activity of kampo (Japanese herbal) medicine "sho
      seiryu-to" and its mode of action.
AB  - When BALB/c mice were treated with a Kampo (Japanese herbal) medicine "Sho-seiryu
      to" (SST) (2 g/kg, 10 times) orally from 7 days before to 4 days after the
      infection and infected with mouse-adapted influenza virus A/PR/8/34 by nasal site
      restricted infection, replication of the virus in the nasal cavity and spread of
      the virus to the lung were efficiently inhibited at 5 days after infection in
      comparison with water-treated mice. However, another Kampo medicine "Kakkon-to"
      showed no anti-influenza virus activity in the same condition. The antiviral IgA
      antibody in the nasal and broncho-alveolar washes of the SST treated mice
      increased significantly in comparison with that of water-treated control. Oral
      administration of SST (2 g/kg, 18 times) from 7 days before to 13 days after
      vaccination also significantly augmented serum hemagglutination-inhibiting
      antibody by nasal inoculation of influenza HA vaccine (5 micrograms/mouse) that
      was insufficient to induce antiviral antibody. SST did not inhibit the
      replication of mouse-adapted influenza virus A/PR/8/34 in Madin-Darby canine
      kidney cells. SST also did not inhibit the influenza virus sialidase activity
      against sodium p-nitrophenyl-N-acetyl-alpha-D-neuraminate and hemagglutination by
      mouse-adapted influenza virus A/PR/8/34. SST showed no influence on interferon
      production in nasal wash of mice at 5 days after the virus infection. These
      results suggest that SST confers better protection against influenza virus
      infection through augmentation of production of antiviral IgA antibody but not
      direct action to the virus, and can be used as an adjuvant to nasally inoculated
      influenza HA vaccine.

PMID- 7527378
TI  - A novel fluorescein-histamine reagent to quantitate histamine receptor expression
      on leucocytes.
AB  - The expression of histamine receptors on the surface of rat lymph node cells was
      studied using a reagent made by directly coupling fluorescein isothiocyanate
      (FITC) to histamine. This approach contrasts with the use of previous reagents,
      made by coupling histamine and fluorescein separately to a protein carrier, which
      bind non-specifically to cells and cause staining unrelated to histamine receptor
      expression. The new reagent was used, in combination with a panel of monoclonal
      antibodies, for the dual staining of rat lymph node cells for two-colour flow
      cytometric analysis to investigate the distribution of histamine receptors on
      different leucocyte subsets. The majority of cells were stained by the FITC
      histamine reagent and these constituted two distinct populations, those with the
      properties of small lymphocytes and a second population which included
      macrophages. Inhibition studies with the drugs mepyramine and cimetidine, which
      are antagonists of H1 and H2 receptors, respectively, showed that most
      lymphocytes possess H1 receptors while the macrophages have H2 receptors. It
      seems that macrophages have a higher number of histamine receptors than the
      majority of lymphocytes, but that they are of lower affinity.

PMID- 7527380
TI  - Behaviorally conditioned modulation of natural killer cell activity: enhancement
      of baseline and activated natural killer cell activity.
AB  - Natural killer (NK) cells comprise a sub-population of lymphocytes functionally
      defined by their ability to spontaneously lyse select tumor and virally infected
      cells. NK cell lytic function is sensitive to modulation by cytokines and
      neuroendocrine mediators. Behavioral conditioning trains an animal to cognitively
      associate a novel environmental cue (i.e. odor) with a physiologically active
      agent (i.e. Polylnosinic:PolyCytidilic acid, Poly I:C). Poly I:C induces
      interferon production resulting in activation of NK cells and enhanced NK cell
      lytic activity. Subsequent to behavioral conditioning, independent presentation
      of the odor should elicit similar responses (enhanced NK cell activity). We have
      shown that animals pre-exposed to the conditioning apparatus or manual restraint
      prior to behavioral conditioning demonstrate enhanced baseline NK cell activity
      or no effects respectively. To assess the influence of NK cell activation in
      conjunction with behavioral conditioning, we have re-presented the odor to
      animals with activated or baseline NK activity. Lymphocytes were then incubated
      for five days with IL-2 and cellular cytotoxic activity re-assessed. Behavioral
      conditioning significantly enhanced baseline and activated NK cell activity in
      animals previously exposed to the conditioning apparatus. No differences in lytic
      activity versus NK sensitive targets were observed following IL-2 activation. In
      contrast, animals manually restrained prior to conditioning showed no differences
      in baseline or in vivo activated NK activity, but previously non-activated
      lymphocytes stimulated with IL-2 demonstrated significantly higher lytic activity
      in conditioned animals re-presented with the odor. These results demonstrate
      central nervous system (CNS) modulation of NK cell activity and the presence of
      an interplay between cytokine activation and responsiveness to CNS
      immunoregulatory signals.

PMID- 7527379
TI  - Antiallergic activity of tylogenin, a novel steroidal compound from Tylophora
      sylvatica.
AB  - Tylogenin, a steroidal aglycone generated by acid hydrolysis from two seasonal
      glycosides occurring in Tylophora sylvatica, inhibits IgE-induced basophil
      mediator release for allergic reactions. In the rabbit basophil-dependent
      serotonin release (BDSR) assay system, the inhibitory activity of tylogenin (geom
      mean IC50 = 39 microM) was significantly (P < 0.05) greater than that of its
      parent glycosides, tylophoroside (geom mean IC50 263 microM) and
      acetyltylophoroside (geom mean IC50 331 microM), and that of dexamethasone (geom
      mean IC50 = 912 microM). The activity of tylogenin was found to increase with the
      incubation time. In the human leukocyte-dependent histamine release (LDHR) test
      model, the glycosides had only a minimal activity. In contrast, tylogenin, with a
      geom mean IC50 = 49 microM, exerted a significantly (P < 0.05) greater potency
      than dexamethasone (IC50 = 257 microM). These results suggest that tylogenin
      could represent a new class of antiallergic agents.

PMID- 7527381
TI  - [Effects and side-effects of corticosteroids].

PMID- 7527382
TI  - [Does transcranial magnetic stimulation provide improved assessment of
      "idiopathic" facial paralysis? Initial results].
AB  - To evaluate transcranial magnetic stimulation (TMS) in patients suffering from
      idiopathic facial palsy, results from 31 patients were reviewed. TMS was applied
      to the facial nerve by parieto-occipital, ipsilateral coil placement. At the time
      of the first examination (2-25 days after the onset of palsy), 11 of 31 nerves on
      the affected side were excitably by TMS. Patients were classified according to
      whether magnetic excitability of the facial nerve was possible (group I) or not
      possible (group II). In general, the percentage of patients with complete or
      nearly complete recovery of facial function was 97% following either a standard
      infusion therapy (corticosteroids, hydroxyethylstarch and pentoxifyllin) or
      orally administered corticoids (equal percentages in each group, respectively).
      In the first group of patients, 11 had facial nerves that were excitable with TMS
      and showed complete recovery of motor function within a median period of 7 weeks.
      In those patients with successful TMS only one experienced "crocodile tears"
      syndrome one year after Bell's palsy but without any further motor deficit of
      facial function. In patients with unresponsive nerve function following TMS 17
      recovered without sequelae (median, 11 weeks), whereas 3 of 20 (15%) developed
      deficits of motor function. Two of these latter cases suffered from synkinesias
      (one that was slight after surgical decompression of the facial nerve and one
      severe) while one had facial contractures but without motor deficits.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7527383
TI  - Hepatic plasmacytoma and biclonal gammopathy in a cat.
AB  - A 13-year-old castrated male domestic shorthair cat was evaluated because of
      weight loss, despite a good appetite. The most remarkable abnormality was a total
      serum protein concentration of 12.4 g/dl, with a globulin concentration of 9.4
      g/dl. Serum protein electrophoresis revealed a biclonal spike in the gamma
      region. At necropsy, 2 discrete plasmacytomas were found in the liver, without
      bone marrow involvement or amyloidosis.

PMID- 7527384
TI  - An enzyme-linked immunosorbent assay (ELISA) for detection of Clostridium
      aldrichii in anaerobiodigesters.
AB  - Monoclonal antibodies (Mabs) against Clostridium aldrichii were prepared by in
      vivo and in vitro immunization with whole cells and produced after fusion as
      ascites in BALB/c mice. An enzyme-linked immunosorbent assay (ELISA) was used to
      test for specificity and sensitivity of the Mabs to detect Cl. aldrichii. The
      lower limit for Cl. aldrichii detection in pure and mixed culture with ELISA was
      10(5) cells ml-1. Twenty other species of bacteria, including 12 cellulolytic
      species, were tested for cross-reactivity with the ELISA, but none was detected.
      The ELISA was used for detection of Cl. aldrichii over a 16-month period in five
      mesophilic continuously-stirred tank reactors (CSTR) with wood, glucose, sludge
      or sorghum as substrates. The population of Cl. aldrichii in the poplar wood
      anaerobic digester effluent was 10(6)-10(7) cells ml-1 over that time. These
      numbers were confirmed by anaerobic microbiological methods. Results from the
      ELISA technique were obtained in 36 h vs 3 weeks for culture methods. It is
      concluded that the ELISA is a useful, time-saving method for identification,
      detection and quantification of Cl. aldrichii in axenic, mixed culture, and in
      complex undefined cultures such as those found in anaerobic digesters.

PMID- 7527385
TI  - Platelet-derived growth factor stimulates phosphorylation of growth factor
      receptor-binding protein-2 in vascular smooth muscle cells.
AB  - Growth factor receptor-binding protein-2 (GRB2) couples growth factor receptor
      activation to the p21ras nucleotide exchange factor son-of-sevenless (SOS). Son
      of-sevenless can serve as a substrate for mitogen-activated protein kinases and
      may be subject to feed back regulation in mitogen-stimulated cells. Herein, we
      demonstrate phosphorylation on GRB2 in rat A10 vascular smooth muscle cells
      exposed to platelet-derived growth factor (PDGF). Lysates from smooth cells
      stimulated with PDGF revealed a shift in the electrophoretic mobility of GRB2.
      Further investigation confirmed that phosphorylation on GRB2 accompanied this
      mobility shift. Phosphorylation on GRB2 was time-dependent and correlated with
      PDGF receptor activation. The time-course for phosphorylation of GRB2 and
      subsequent decay corresponded with other events characteristic of platelet
      derived growth factor signaling. GRB2 was not phosphorylated in cells treated
      with phorbol 12-myristate 13-acetate, and down-regulation of protein kinase C
      failed to attenuate phosphorylation on GRB2 in response to growth factor.
      Analysis of GRB2 immune complexes revealed a kinase activity capable of
      phosphorylating GRB2 in vitro and demonstrated that the kinase activated in
      response to PDGF may physically associate with GRB2 signaling complexes.

PMID- 7527386
TI  - Angiotensin II stimulates sis-inducing factor-like DNA binding activity. Evidence
      that the AT1A receptor activates transcription factor-Stat91 and/or a related
      protein.
AB  - Recent studies on cytokine and growth factor stimulated signal transduction have
      defined a direct pathway (Stat91) linking cell surface receptors to target genes
      in the nucleus. The Stat91 pathway regulated c-fos gene transcription involves
      activation by tyrosine phosphorylation of the DNA binding factor SIF (sis
      inducing factor) in the cytoplasm, its nuclear translocation, and interaction
      with the regulatory element SIE (sis-inducing element). SIF is a complex of
      proteins containing members of the STAT family of transcription factors. We
      determined whether angiotensin II (AII), which acts as a growth factor in many
      cell types, could activate the Stat91 pathway. We used neonatal rat cardiac
      fibroblasts expressing G-protein linked AII receptors and CHO-K1 cells expressing
      stably transfected angiotensin type 1A (AT1A) receptors to address this question.
      Angiotensin II induced SIF-like activity in both cell types, with initial
      induction at 15-30 min, maximal around 2-3 h, and undetectable at 6 h.
      Cytoplasmic and nuclear fractions from cells exposed to AII contained DNA binding
      activity to SIE. The SIF activity was insensitive to protein synthesis inhibitors
      and sensitive to the tyrosine kinase inhibitor genistein. Stat91 or a related
      protein was identified as a component of the AII-induced SIF complex and
      increased levels of this tyrosine-phosphorylated protein were found in nuclear
      extracts of cells treated with AII. This is the first evidence that a seven
      transmembrane, G-protein-coupled receptor, namely AT1A, activates the Stat91
      nuclear signaling pathway.

PMID- 7527387
TI  - Substrate specificity of an RNase III-like activity from Bacillus subtilis.
AB  - Bacillus subtilis bacteriophage SP82 codes for several early RNAs that were shown
      previously to be cleaved by an RNase III-like enzyme called "Bs-RNase III."
      Cloning of DNA fragments that encode these RNA sequences downstream of a T7 RNA
      polymerase promoter allowed the synthesis of substrates that were used to test
      the cleavage specificity of Bs-RNase III, which was purified from a protease
      deficient strain of B. subtilis. Single nucleotide changes at or near the
      cleavage site and deletions upstream and downstream of the cleavage site were
      constructed. The effects of these changes on the rate of Bs-RNase III cleavage
      were measured. The activity of Bs-RNase III and Escherichia coli RNase III on
      heterologous substrates was also tested. Although the local environment of the
      site of Bs-RNase III cleavage appears very similar to that of E. coli RNase III,
      there are important differences in their substrate specificity.

PMID- 7527389
TI  - Heat shock-induced phosphorylation of GroEL alters its binding and dissociation
      from unfolded proteins.
AB  - During heat shock of Escherichia coli, the expression of the major molecular
      chaperone, GroEL, increases; in addition, a small fraction of the GroEL becomes
      phosphorylated (Sherman, M. Yu., and Goldberg, A. L. (1992) Nature 367, 166
      1692). This heat shock-induced phosphorylation was found to enhance 50-100-fold
      the capacity of GroEL to bind to several denatured proteins, including casein and
      fetuin. The phosphorylated species in the cell extract bound quantitatively to
      affinity columns containing these ligands, and treatment of the extract with
      alkaline phosphatase markedly reduced this binding. Like heat shock (42 degrees
      C), overproduction of GroEL (5-10-fold) from the multicopy plasmid at low
      temperature (25 degrees C) increased the phosphorylated fraction, which bound
      strongly to denatured fetuin. Heat shock of these cells further enhanced
      phosphorylation, and about 15% of the induced level of GroEL could bind tightly
      to the fetuin column. The predominant form of the GroEL that bound to the
      denatured protein columns appeared to contain at least one phosphate on each of
      its subunits, although multiple phosphorylated subunits were also observed. With
      fetuin and casein as affinity ligands, only the phosphorylated species bound, and
      this material dissociated quantitatively upon addition of ATP-Mg2+. With CRAG and
      histone as the ligands, some unphosphorylated GroEL also bound, but this species
      (unlike the phosphorylated form) was not released by ATP alone; its release
      required the addition of the cofactor GroES together with ATP. Thus, the
      phosphorylation of GroEL during heat shock greatly enhances its ability to bind
      to certain denatured proteins and stimulates its ATP-dependent dissociation in
      the absence of GroES. Presumably, these alterations in the properties of a
      fraction of GroEL aid in the refolding or the degradation of specific damaged
      polypeptides.

PMID- 7527390
TI  - Cloning and biochemical characterization of a plant protein kinase that
      phosphorylates serine, threonine, and tyrosine.
AB  - Phosphorylation of proteins on serine, threonine, or tyrosine residues represents
      an important biochemical mechanism to regulate the activity of enzymes and is
      used in many cellular processes. In animals, protein serine/threonine and protein
      tyrosine kinases are known to perform essential roles in many pathways that
      transmit external stimuli from the cell surface to the cell inferior and the
      nucleus. In plants, although an increasing number of protein serine/threonine
      kinases have been cloned, the existence of protein tyrosine kinases remains yet
      to be demonstrated. Here, we report the cloning and biochemical characterization
      of a plant protein kinase, Arabidopsis dual specificity kinase 1 (ADK1), using a
      functional screening method, namely by screening an Arabidopsis expression
      library with antiphosphotyrosine antibodies. Four independent cDNA clones that
      define a polypeptide of 319 amino acids length with homology to protein kinases
      were identified in this screen. Phosphoamino acid analysis of the
      autophosphorylated kinase shows that ADK1 phosphorylates serine, threonine, and
      tyrosine. Using poly (Glu/Tyr) as a substrate, we confirm that ADK1 is capable of
      phosphorylating tyrosine residues.

PMID- 7527391
TI  - Independent binding of peptide ligands to the SH2 and SH3 domains of Grb2.
AB  - Grb2, composed entirely of SH2 and SH3 domains, serves as an adaptor protein in
      signaling from growth factor-activated tyrosine kinase receptors. It interacts
      via its SH2 domain with the autophosphorylated carboxyl-terminal tail of
      activated epidermal growth factor (EGF) receptor and via its SH3 domains with
      proline-rich sequences in the Ras guanine nucleotide releasing factor, Son of
      sevenless (Sos). Recruitment of the Grb2-Sos complex to the receptor upon its
      stimulation leads to Ras activation. A major question remains as to whether SH2
      mediated binding of Grb2 to the activated receptor results in conformational
      changes that influence its SH3-mediated association with Sos, thereby affecting
      Sos activity. This question is addressed through studies of the binding to intact
      Grb2 of an EGF receptor-derived phosphotyrosine-containing peptide and a Sos
      derived proline-rich peptide using isothermal titration calorimetry and surface
      plasmon resonance measurements. The phosphopeptide binds to Grb2 in a 1:1
      complex, with a KD of 0.4 microns. The Sos proline-rich peptide binds to Grb2 in
      a 2:1 complex, with a KD of 22 microns. Saturation of the SH2 domain of Grb2 with
      the EGFR phosphopeptide was found not to affect its subsequent binding to the Sos
      peptide. Thus we detected no influence of SH2 binding upon SH3-mediated
      interactions, suggesting that the domains do not communicate, and that
      recruitment itself of Sos to the cell surface is sufficient for Ras signaling.

PMID- 7527388
TI  - Tyrosine phosphorylation of a M(r) 38,000 A/B-type hnRNP protein selectively
      modulates its RNA binding.
AB  - The M(r) 38,000 RNA-binding protein (P38) is the major component of
      translationally repressed messenger ribonucleoproteins in cryptobiotic gastrulae
      of the brine shrimp Artemia. Partial elucidation of the amino acid sequence of
      P38 reveals that it is homologous to A/B-type hnRNP proteins. This was confirmed
      by immunodetection with antibodies specific for A/B-type hnRNP proteins from
      Drosophila melanogaster. P38 can be phosphorylated in vitro by a src-related
      protein tyrosine kinase on multiple tyrosine residues located predominantly in
      the glycine-rich domain. Tyrosine phosphorylated P38 can be efficiently
      dephosphorylated by a specific protein tyrosine phosphatase (1B-like) and by
      protein phosphatase 2A activated by the phosphotyrosyl phosphatase activator.
      Tyrosine phosphorylation of P38 slightly influences its subsequent
      phosphorylation by casein kinase II. The latter phosphorylation site is located
      in the glycine-rich domain of P38. Two-dimensional gel electrophoresis resolves
      P38 into multiple isoforms which shift to more acidic pI values after
      phosphorylation by protein tyrosine kinase or casein kinase II. From
      nitrocellulose filter binding and UV cross-linking analysis, evidence was
      obtained that tyrosine phosphorylation of P38 impairs its binding to poly(A) but
      not to poly(U). This demonstrates the involvement of tyrosine residues in
      polynucleotide-specific RNA binding that can be regulated by
      phosphorylation/dephosphorylation.

PMID- 7527392
TI  - Convergence of signaling by interleukin-3, granulocyte-macrophage colony
      stimulating factor, and mast cell growth factor on JAK2 tyrosine kinase.
AB  - Mast cell growth factor (MGF) (also called stem cell factor) synergizes with
      several lymphokines, including interleukin-3 (IL-3) and granulocyte-macrophage
      colony-stimulating factor (GM-CSF), to promote proliferation and differentiation
      of certain hemopoietic progenitor cells. Although similar patterns of tyrosine
      phosphorylated proteins characterize cells stimulated by MGF, IL-3, and GM-CSF,
      only the MGF receptor is a tyrosine kinase, and the heterodimeric receptors for
      IL-3 and GM-CSF share a common beta subunit that is devoid of enzymatic activity.
      Here we show that signaling pathways utilized by all three cytokines include the
      cytoplasmic tyrosine kinase JAK2. Analysis of several factor-dependent myeloid
      cell lines indicated that JAK2 is physically associated with the common beta
      subunit and with MGF receptor (c-Kit) even prior to ligand binding. However, each
      of the ligands induced elevated tyrosine phosphorylation of JAK2 and a consequent
      increase in its catalytic activity. These results demonstrate for the first time
      the convergence within the same myeloid cells of signaling pathways originating
      in two distinct lymphokine receptors and a tyrosine kinase receptor on activation
      of a cytoplasmic tyrosine kinase.

PMID- 7527393
TI  - Peptide inhibitors of src SH3-SH2-phosphoprotein interactions.
AB  - Activated pp60c-src has been implicated in a number of human malignancies
      including colon carcinoma and breast adenocarcinoma. Association of the src SH2
      domain with tyrosine-phosphorylated proteins plays a role in src-mediated signal
      transduction. Inhibitors of src SH2 domain-phosphoprotein interactions are, thus,
      of great interest in defining the role(s) of src in signal transduction pathways.
      To facilitate such studies, an enzyme-linked immunosorbent assay (ELISA) was
      developed to detect inhibitors of src SH2-phosphoprotein interactions. This assay
      measures inhibition of binding of a fusion construct (glutathione S-transferase
      src SH3-SH2) with autophosphorylated epidermal growth factor receptor tyrosine
      kinase domain. Activities of phosphopeptide segments derived from potential src
      SH2 cognate phosphoprotein partners were determined, with the focal adhesion
      kinase-derived segment VSETDDY*AEIIDE yielding the highest inhibitory activity.
      Structure activity studies starting from acetyl (Ac)-Y*EEIE have identified Ac
      Y*Y*Y*IE as the most active compound screened in the ELISA. This compound is at
      least 20-fold more active than the parent peptide Ac-Y*EEIE. A high resolution (2
      A) crystal structure of human src SH2 complexed with Ac-Y*EEIE was obtained and
      provided a useful framework for understanding the structure-activity
      relationships. Additionally, Ac-Y*EEIE was able to block interactions between src
      and its cellular phosphoprotein partners in vanadate-treated cell lysates from
      MDA-MB-468 breast carcinoma cells. However, it is unable to abrogate
      proliferation of MDA-MB-468 cells in culture, presumably because of poor cell
      penetration and/or lability of the phosphate group on tyrosine.

PMID- 7527394
TI  - Intact and functional fibroblast growth factor (FGF) receptor-1 trafficks near
      the nucleus in response to FGF-1.
AB  - Exogenous fibroblast growth factor-1 (FGF-1) associates with the nucleus in a
      receptor-dependent manner during the entire G1 period of the BALB/c 3T3 cell
      cycle (Zhan, X., Hu, X., Friesel, R., and Maciag, T. (1993) J. Biol. Chem. 268,
      9611-9620). To further study the role of the FGF receptor (FGFR) during this
      translocation, the intracellular fate of FGFR-1 protein and enzymatic activity
      was examined. Immunoprecipitation using multiple FGFR-1 antibodies followed by an
      in vitro tyrosine kinase activity assay enabled us to identify FGFR-1 as a 130
      kDa phosphotyrosine-containing protein associated with the nuclear fraction of
      NIH 3T3 cells exposed to FGF-1. While FGFR-1 tyrosine kinase activity could be
      detected as a nuclear-associated protein after a 2-h exposure of the NIH 3T3
      cells to FGF-1, this activity appeared to be maximal in the nuclear fraction
      between 4 and 12 h after FGF-1 treatment. In addition, analysis by confocal
      immunofluorescence microscopy of quiescent and FGF-1-stimulated NIH 3T3 cells
      reveal a prominent perinuclear FGFR-1 staining pattern in the cells exposed to
      FGF-1 but not in the quiescent population. We also observed FGFR-1 associated
      with the nuclear fraction in FGFR-1-transfected L6 rat myoblasts, which are known
      to be refractive to exogenous FGF-1 and express relatively low levels of
      endogenous FGFR-1. In addition, these cells also exhibited the presence of a 145
      kDa phosphoprotein in the nuclear fraction that was recognized by FGFR-1
      antibodies. These results suggest that the FGFR-1 may be translocated near the
      nucleus upon interaction with its ligand during the entire G1 period of the NIH
      3T3 cell cycle as a structurally intact and functional tyrosine kinase that may
      be accessible to perinuclear polypeptides as a regulatory enzyme.

PMID- 7527395
TI  - Transcription factor-induced, phased bending of the E-selectin promoter.
AB  - E-selectin is an endothelial adhesion molecule that is critically involved in
      neutrophil adhesion and recruitment. All DNA elements required for interleukin-1
      inducibility have been located in the proximal promoter: an NF-ELAM1/ATF site,
      two NF-kappa B sites (I and II), the NF-ELAM2 element and a TATA box. We show
      here that interleukin-1 induced promoter activity is exquisitely sensitive to the
      spatial arrangements of these elements. Phasing of the ATF and NF-kappa B II
      elements indicates that their relative helix orientation is more important than
      distance per se. This sensitivity is partly due to a requirement for correctly
      oriented, transcription factor-induced DNA-bending. (i) Band shift analyses with
      permuted ATF- and NF-kappa B elements show that their associated factors all bend
      DNA. (ii) One can functionally replace the NF-ELAM1/ATF element by a subset of a
      panel of DNA fragments that contain defined bends in various planes. We conclude
      that the main role of the factors binding at the NF-ELAM1/ATF element is to alter
      the conformation of the E-selectin promoter, presumably looping distant enhancer
      elements into each other's proximity.

PMID- 7527397
TI  - Hepatocyte growth factor/scatter factor induces tyrosine phosphorylation of focal
      adhesion kinase (p125FAK) and promotes migration and invasion by oral squamous
      cell carcinoma cells.
AB  - Fibroblasts or their conditioned medium stimulated invasion by squamous cell
      carcinoma cells. The fibroblast-derived activity responsible for increased
      invasion is the hepatocyte growth factor/scatter factor (HGF/SF), a ligand for
      the c-Met receptor. HGF/SF stimulated migration of the cells on various
      extracellular matrix substrates but did not alter their adhesion efficiency nor
      integrin expression. HGF/SF stimulated motility in a two step process: initially
      cells spread rapidly and formed focal adhesions, and then they disassembled these
      condensations, which was followed by increased cell locomotion. The focal
      adhesions contained vinculin, p125FAK, beta 1 integrin, and phosphotyrosine.
      Within minutes after exposure of cells to HGF/SF, proteins of 125 and 145 kDa
      showed elevated tyrosine phosphorylation and were identified as p125FAK and c
      Met, respectively. Gradual loss of tyrosine phosphorylation coincided with
      disruption of focal adhesions and conversion to a motile phenotype. HGF/SF
      mediated tyrosine phosphorylation of p125FAK was inhibited by the tyrosine kinase
      inhibitor, herbimycin A, which also blocked spreading and the migratory response.
      These results indicate that fibroblast-derived HGF/SF triggers migration through
      the initial recruiting of integrins, cytoskeletal proteins, and p125FAK into
      focal adhesions that is dependent on tyrosine kinase activity.

PMID- 7527399
TI  - 3-Hydroxy-3-methylglutaryl-CoA lyase is present in mouse and human liver
      peroxisomes.
AB  - 3-Hydroxy-3-methylglutaryl (HMG)-CoA metabolism is compartmentalized in
      mitochondria, endoplasmic reticulum, and peroxisomes. We investigated the
      subcellular distribution of HMG-CoA lyase (HL), which is found principally in
      mitochondria but in which we observed the potential peroxisomal targeting motif
      cysteine-lysine/arginine-leucine at the carboxyl terminus. We used differential
      and density gradient centrifugation to separate peroxisomes and mitochondria in
      liver homogenates of outbred CD-1 mice. Peroxisomal fractions contained 6.4% of
      total HL activity in mouse liver and 5.6% in human liver. Liver peroxisomal HL
      activity increased 2.3-2.5 times following induction of peroxisomal proliferation
      by clofibrate administration. Western blotting with anti-human HL antibodies
      confirmed the presence of immunoreactive HL in peroxisomal fractions. Mouse liver
      peroxisomal HL is distinct from mitochondrial HL, measuring approximately 2.5 kDa
      more by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. By fast
      protein liquid chromatofocusing analysis, the pI of peroxisomal HL is 7.3, in
      contrast to 6.2 for mitochondrial HL. These results are consistent with
      noncleavage of the mitochondrial leader peptide in peroxisomal HL. A distinct
      species of enzymatically active HL exists in peroxisomes and may play a role in
      HMG-CoA metabolism in that organelle.

PMID- 7527398
TI  - Interleukin-1 activates p54 mitogen-activated protein (MAP) kinase/stress
      activated protein kinase by a pathway that is independent of p21ras, Raf-1, and
      MAP kinase kinase.
AB  - In KB epidermoid cells, we previously showed that interleukin-1 alpha (IL-1) and
      various mitogens activate the mitogen-activated protein (MAP) kinases ERK1 and
      ERK2, which phosphorylate both myelin basic protein (MBP) and a peptide
      containing Thr669 of the epidermal growth factor receptor. In cell-free extracts
      made from gingival fibroblasts treated with platelet-derived growth factor or
      HepG2 hepatoma cells stimulated with phorbol myristate acetate, MBP and Thr669
      kinase were both elevated 4-fold, and ERK1 and ERK2 were tyrosine-phosphorylated.
      In these cells IL-1 activated a kinase(s) that phosphorylated Thr669 peptide but
      not MBP and failed to cause tyrosine phosphorylation of ERK1/ERK2. Ceramide has
      been proposed as an intracellular mediator of IL-1 action, but C2-ceramide or
      sphingosine stimulated predominantly MBP-specific kinase activity in fibroblasts
      and had no effect in HepG2 cells. p54 MAP kinase (also called stress-activated
      protein kinase) is a c-Jun kinase first isolated from livers of cycloheximide
      treated rats. After IL-1 stimulation, immunoprecipitates of lysates made from all
      three cell types with specific anti-p54 MAP kinase serum contained Thr669 and c
      Jun phosphorylating activity, whereas precipitates from unstimulated cells
      contained no detectable p54 kinase activity. The major peak of IL-1-stimulated
      HepG2 Thr669 kinase activity co-chromatographed on Mono Q and phenyl-Superose
      with immunodetectable p54 MAP kinase. IL-1 did not cause p21ras activation in any
      cell type. Induction of Thr 669 kinase activity was not abrogated by elevation of
      cAMP levels, which has been shown to interfere with the activation of Raf-1. We
      could not detect MAP kinase kinase phosphorylating activity in unfractionated
      lysates made from IL-1-stimulated fibroblasts or HepG2 cells. KB cells contained
      a small amount of this activity, but it was not precipitated with an anti-Raf-1
      antibody. We conclude that most of the IL-1-activated Thr669 kinase activity in
      fibroblasts and HepG2 cells, and a portion in KB cells, is due to p54 MAP kinase
      and that its activation is Ras-, Raf-, and MAP kinase kinase-independent.

PMID- 7527400
TI  - The effect of eight V2 vasopressin receptor mutations on stimulation of adenylyl
      cyclase and binding to vasopressin.
AB  - We previously identified six V2 vasopressin receptor mutations in five unrelated
      nephrogenic diabetes insipidus (NDI) families. In order to elucidate the effect
      of these mutations on the function of the V2 vasopressin receptor, we introduced
      these six and two additional, naturally occurring mutations into the V2
      vasopressin receptor gene by in vitro mutagenesis. Five of the mutants (two
      frameshift, one nonsense, and two missense) failed to stimulate adenylyl cyclase
      due to their inability to bind vasopressin under the experimental conditions. In
      contrast, ligand binding and cAMP accumulation were normal for two other
      mutations, a A61V missense mutation and an in-frame deletion of four amino acids
      (Arg-247 to Gly-250), suggesting that they are not the cause of NDI in these
      families. The deletion mutation was found in a family in conjunction with a
      second mutation, R181C, which yielded a much reduced ligand-binding capacity. The
      KD of R181C was at least 26 times higher than that of the wild type. Further
      characterization by an immunofluorescent assay showed that the R181C mutant
      receptor is expressed and distributed on the cell surface in a manner similar to
      that of the wild type. This finding indicates that the inability of this mutant
      to stimulate adenylyl cyclase is caused by the reduced capacity for vasopressin
      binding and that the R181C mutation is responsible for NDI in this family.

PMID- 7527396
TI  - Tektins are heterodimeric polymers in flagellar microtubules with axial
      periodicities matching the tubulin lattice.
AB  - Tektins are proteins that copartition with tubulin in a stable ribbon of three
      protofilaments from ciliary and flagellar microtubules. After purification,
      tektins A, B, and C from sea urchin sperm flagellar microtubules appear as
      extended relatively insoluble filaments, < 5 nm in diameter. We used cross
      linking reagents to investigate the associations and structural organization of
      subunits within tektin polymers isolated from stable protofilament ribbons of
      Strongylocentrotus purpuratus. We show by SDS-polyacrylamide gel electrophoresis,
      immunoblots, and transmission electron microscopy that tektins are continuous
      heteropolymers in the stable protofilament ribbons, and thus flagellar
      microtubules. Our results also provide evidence for the arrangement of different
      tektin polypeptides within "core" filaments containing equimolar tektins A and B.
      Treatment of these core filaments with bis(sulfosuccinimidyl)suberate and with 1
      ethyl-3-(3-dimethylaminopropyl)carbodiimide yielded a predominant cross-linked
      approximately 106-kDa heterodimer of tektins A and B; similar results were
      obtained by glutaraldehyde cross-linking of tektins solubilized under mild
      conditions. Finally, cross-linking with 3,3'
      dithiobis(sulfosuccinimidylpropionate) revealed a 16 nm periodicity in isolated
      tektin AB filaments that can be related to the 8 nm tubulin dimer lattice and to
      periodically associated microtubule components.

PMID- 7527401
TI  - Mechanism of down-regulation of c-kit receptor. Roles of receptor tyrosine
      kinase, phosphatidylinositol 3'-kinase, and protein kinase C.
AB  - The receptor tyrosine kinase Kit and Kit ligand (KL), encoded at the murine white
      spotting (W) and steel (Sl) loci, respectively, function in hematopoiesis,
      melanogenesis, and gametogenesis. To understand the mechanism of turnover of Kit
      in mast cells, mutant receptors generated in vitro were heterologously expressed
      in Wsb/Wsh mast cells lacking endogenous c-kit expression, and the effects of
      mutations on KL-induced internalization and ubiquitination/degradation of Kit
      were studied. Upon binding of KL, KL.Kit receptor complexes were rapidly
      internalized, and the turnover was accelerated by ubiquitin-mediated degradation.
      Inactivation of the Kit kinase resulted in a reduced rate of internalization of
      KL.Kit complexes, degradation of kinase-inactive receptor complexes was
      relatively slow, and receptor ubiquitination was absent. But abolishment of KL
      induced receptor association and activation of phosphatidylinositol 3'-kinase and
      of tyrosine 821 autophosphorylation did not affect KL-induced internalization and
      ubiquitination/degradation of Kit. Furthermore, Kit receptors can be down
      regulated by proteolytic cleavage induced by either activation of protein kinase
      C or by isopropyl alcohol. In summary, KL-induced internalization of KL.Kit
      complexes and ubiquitination/degradation require an active kinase. By contrast,
      proteolytic cleavage of Kit mediated by protein kinase C activation is
      independent of kinase activity.

PMID- 7527402
TI  - The microarchitecture of the axis as the predisposing factor for fracture of the
      base of the odontoid process. A histomorphometric analysis of twenty-two autopsy
      specimens.
AB  - The axis from twenty-two cadavera was removed at autopsy and was sectioned in the
      sagittal plane to a thickness of one millimeter with use of a surface-stained
      block-grinding technique. Combined two and three-dimensional analysis included an
      evaluation of the volume of the trabecular bone, the trabecular interconnection,
      and the cortical thickness as well as qualitative investigation of the structure
      of the cancellous bone. The body of the axis, the base of the odontoid process,
      and the odontoid process were analyzed separately. The base of the odontoid
      process is a region of least resistance for fractures because of its unique
      microarchitecture. The mean volume of trabecular bone of the base of the odontoid
      process is 55 per cent less than that of the axis and the odontoid process. The
      base also has a markedly poorer trabecular interconnection and a cortical
      thickness that is one-third that of the odontoid process. In all of the
      specimens, trabeculae that were disconnected from the trabecular lattice
      (trabeculae with free ends) were demonstrated in the base of the odontoid
      process. The formation of microcallus in six (27 per cent) of the specimens
      supports the hypothesis that microfractures occur as a result of stress peaks,
      mechanical fatigue, and the relative insufficiency of bone in the static
      condition. Therefore, the base of the odontoid process can be considered as a
      site of predilection for fractures.

PMID- 7527404
TI  - A rapid protein A binding radioimmunoassay for the evaluation of antiviral
      agents.
AB  - A simple, rapid and quantitative protein A binding radioimmunoassay (RIA) was
      developed to screen and evaluate antiviral drugs against human cytomegalovirus
      (HCMV) replication. It was found that (S)-1-[(3-hydroxy-2
      phosphonylmethoxy)propyl]cytosine (HPMPC) and human gamma-interferon (IFN) were
      more effective than 9-[(1-3-dihydroxy-2-propoxy)methyl]guanine (DHPG) and other
      IFNs against HCMV replication in human fibroblast cells. The block in virus
      replication was not due to toxic effect of these compounds on human fibroblast
      cells. The results were in good agreement with those of other workers. The
      results indicate that protein A binding RIA can be useful for rapid and
      quantitative screening of compounds effective against HCMV replication.

PMID- 7527405
TI  - Assessment of epitope-blocking assays for measuring antibody to rotavirus.
AB  - Criteria for determining the presence of antibody and of a response to infection
      in the epitope-blocking assay for anti-rotavirus antibody were evaluated using
      222 sera from children younger than 30 months of age. The children were monitored
      for rotavirus diarrhea by means of daily symptom records and weekly stool
      specimen collection, whether or not symptoms occurred. Sera were collected at 6
      month intervals. Forty-three serum pairs were collected before and after
      documented rotavirus infections. The remaining 136 sera were collected from
      children with no identified infections in the monitoring interval. Use of a 50%
      cutoff-point, as in prior reports, was too stringent a criterion for determining
      the presence of blocking antibody. The absolute percent blocking at the 1:10
      serum dilution was a better measure of antibody content than end-point titration
      using the 50% cutoff-point.

PMID- 7527403
TI  - Therapeutic progress. II: Treatment of psoriasis.
AB  - Treatment of psoriasis is rapidly changing with improved understanding of the
      pathogenesis of the disease. Newer topical preparations such as calcipotriol and
      immunosuppressive agents such as cyclosporin A and FK506 are having a major
      impact on the therapy of psoriasis. This article reviews the conventional
      therapies and newer agents used in the treatment of this common dermatosis.

PMID- 7527406
TI  - Effects of 17 beta-estradiol on circulating adhesion molecules.
AB  - The effects of 17 beta-estradiol (E2) on the serum levels of the circulating
      endothelial-leukocyte, intercellular, and vascular adhesion molecules [ELAM-1,
      ICAM-1 (CD54), and VCAM-1] were evaluated in healthy male volunteers after single
      im injection of 10 mg E2 valerate. In addition, a time course of the effects of
      E2 on circulating adhesion molecules (AMs), cortisol serum levels, differential
      blood counts, and surface expression of the lymphocyte function-associated
      antigen-1 (CD11a/CD18), CD3, CD4, CD19, and CD25 on leukocytes was studied in
      another group of volunteers. A 5% decrease in circulating ICAM-1 (P = 0.045 vs.
      placebo) was found when a single time point (96 h after E2 injection) was
      studied. However, this decrease was smaller than the intrasubject (day to day)
      variability observed, and there was no consistent and time-dependent effect of E2
      on circulating AMs. Circulating neutrophils increased 2.3-fold over baseline
      after E2 treatment (P = 0.0008 vs. placebo). The mean coefficients of variation
      for the intrasubject (day to day) and intersubject variability of circulating AMs
      were between 5.4-7.5% and 20-29%, respectively. Our findings indicate that the
      effect of E2 on circulating AMs is not distinguishable from the intrasubject
      variability observed after placebo treatment. Thus, an effect of E2 on adhesion
      molecules is unlikely to contribute to the antiatherogenic-cardioprotective
      effect of E2. The pronounced E2-mediated increase in neutrophils deserves further
      studies to elucidate its (patho-)physiological implications.

PMID- 7527407
TI  - Exclusion of two major areas on thyroid peroxidase from the immunodominant region
      containing the conformational epitopes recognized by human autoantibodies.
AB  - We have used a chimeric molecule between thyroid peroxidase (TPO) and
      myeloperoxidase (MPO) as well as new information on the three-dimensional
      structure of MPO to refine further our understanding of the location of the TPO
      immunodominant region recognized by TPO autoantibodies in patients' sera. In TPO
      MPO chimera A, the amino-terminal 146 amino acids of MPO substitute for the amino
      terminal 121 amino acids of TPO. We performed fluorescence-activated cell sorter
      analysis of Chinese hamster ovary cells expressing TPO-MPO-A on their surface
      using four monoclonal human autoantibody F(ab) (WR1.7, TR1.8, TR1.9, and SP1.4)
      that define the immunodominant region. All four F(ab) recognized the TPO-MPO-A
      chimeric molecule to the same extent. In a second approach to refine the location
      on the TPO-immunodominant region, we compared the ability of the TPO autoantibody
      F(ab) to inhibit the binding of serum autoantibodies to the monomeric and dimeric
      forms of human TPO. The F(ab) inhibited equally (approximately 80%) the binding
      to the TPO monomer and dimer by autoantibodies in the sera of six individual
      patients. The present observations exclude two major regions of TPO from the
      autoantibody-immunodominant region, namely the amino-terminal 121 amino acids of
      the TPO extracellular domain and the contact region between the two TPO monomers.
      These findings together with previous data on the Mab47/C21 region of TPO and the
      recently elucidated 3-dimensional structure of highly homologous MPO, narrow, by
      a process of exclusion, the site on TPO comprising the immunodominant region. The
      data provide further support for the thesis, still controversial, that the
      majority of TPO autoantibodies recognize the native molecule.

PMID- 7527408
TI  - Insulin-like growth factor system gene expression in human endometrium during the
      menstrual cycle.
AB  - To study the cellular patterns of gene expression of the insulin-like growth
      factor (IGF) system in human endometrium during the menstrual cycle, we used in
      situ hybridization histochemistry to localize messenger ribonucleic acids (mRNAs)
      encoding IGF-I and -II, their receptors, and their binding proteins (IGFBPs) in
      fresh-frozen endometrial tissue obtained from cycling women. IGF-I and IGF-II
      mRNAs are both expressed diffusely throughout endometrial stroma and are not
      detected in endometrial epithelium. Endometrial IGF-I mRNA is significantly more
      abundant during the proliferative than the secretory phase of the menstrual
      cycle, whereas the reverse is true for IGF-II. Type I and type II IGF receptor
      mRNAs are both present in endometrial stroma, but are relatively more abundant in
      endometrial epithelium, and neither shows distinctive cyclic changes. IGFBP-2, 
      4, -5, and -6 mRNAs demonstrate a diffuse stromal pattern of expression, whereas
      IGFBP-1 and -3 are more focally concentrated in selected subpopulations of
      endometrial cells. IGFBP-1 mRNA is not detected in proliferative endometrium and
      demonstrates a very heterogeneous pattern of expression in secretory endometrium,
      where it is intensely abundant in a patchy distribution of stromal and epithelial
      cells. IGFBP-3 mRNA is primarily concentrated in endometrial capillaries and is
      increased in the secretory phase, largely due to the intense vascularization of
      endometrial glands during this phase. IGFBP-5 mRNA is more abundant in the
      proliferative phase, but all other IGFBP mRNAs are relatively increased in the
      secretory phase of the menstrual cycle. These findings support the view that the
      IGF system plays a fundamental role in endometrial biology, acting via autocrine
      and/or paracrine mechanisms, with IGF-I and IGFBP-5 being dominant in the
      proliferative phase, and IGF-II and the other IGFBPs predominant in the secretory
      phase of the menstrual cycle.

PMID- 7527409
TI  - The phosphorylation pattern of insulin-like growth factor-binding protein-1 in
      normal plasma is different from that in amniotic fluid and changes during
      pregnancy.
AB  - We have determined the phosphorylation pattern of circulating insulin-like growth
      factor-binding protein-1 (IGFBP-1) in normal subjects and assessed how this
      changes in pregnancy. Two RIAs employing different monoclonal antibodies (MAbs
      6303 or 6305) were used to measure IGFBP-1. In normal subjects, RIA 6303 measured
      11-fold higher levels than RIA 6305 (72.8 vs. 6.6 micrograms/L; P < 0.008).
      However, in amniotic fluid (AF), the two assays gave similar results.
      Immunoprecipitation of plasma and AF with MAb 6303 and 6305 before nonsodium
      dodecyl sulfate-electrophoresis and Western ligand blotting revealed different
      IGFBP-1 isoforms and differential antibody recognition as the cause of this
      discrepancy. In AF, both MAbs precipitated nonphosphorylated and phosphorylated
      isoforms, whereas in plasma, only a single highly phosphorylated species, not
      seen in AF, was observed. This form of IGFBP-1 was precipitated by MAb 6303 only.
      During pregnancy, the phosphorylation state of IGFBP-1 in the maternal
      circulation was altered, as nonphosphorylated IGFBP-1 and three lesser
      phosphoforms were also observed. The appearance of these other variants resulted
      in a significant increase in IGFBP-1 measured by RIA 6305 (37, 51, and 83
      micrograms/L in first, second, and third trimesters, respectively; P < 0.0005 vs.
      controls). The changes in IGFBP-1 phosphorylation induced by pregnancy may
      influence the modulatory effects of IGFBP-1 on IGF bioavailability and, hence,
      fetal growth.

PMID- 7527410
TI  - Regulation of extragonadal insulin-like growth factor-binding protein-3 by
      testosterone in oophorectomized women.
AB  - Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is the principal
      carrier protein of IGF-I in the circulation. IGF-I has been postulated to play a
      role in the genesis and maintenance of the polycystic ovary syndrome. Regardless
      of the exact mechanism of action of IGF-I on ovarian steroidogenesis, alterations
      in the level of IGFBP-3 may play a significant role in regulating the
      concentration of IGF-I in hyperandrogenism. We have postulated that androgens
      reduce the circulating IGFBP-3 concentration through a mechanism similar to its
      suppression of the hepatic production of sex hormone-binding globulin (SHBG),
      thereby increasing bioavailable IGF-I and amplifying its impact on ovarian
      steroidogenesis. To test this hypothesis, we studied seven oophorectomized women
      (aged 39-51 yr; body mass, 20.9-35.8 kg/m2) during 3 weeks of testosterone (T)
      propionate administration (20 mg, three times weekly). All subjects were
      receiving 0.625 or 1.25 mg conjugated estrogens/day. Blood was sampled before
      (week 0), during (weeks 1-3), and after (week 4) T administration. Serum was
      assayed for total T, GH, and SHBG, and plasma was assessed for IGF-I, insulin
      (INS), and IGFBP-3. IGFBP-3 was measured by both RIA and Western ligand blotting;
      (expressed as a percentage of the control value). Circulating T increased from
      1.51 +/- 1.06 to 30.8 +/- 13.8 mmol/L by week 2 (P < 0.001). During T
      administration, IGF-I increased (from 55 +/- 23 ng/mL at week 0 to 124 +/- 37
      ng/mL at week 4; P < 0.05); INS did not change, with the exception of a higher
      fasting level 1 week after discontinuing therapy, and GH decreased (from 1.7 +/-
      2.3 micrograms/L at week 0 to 0.4 +/- 0.4 microgram/L at week 4; P < 0.03), as
      did the circulating SHBG concentration (397 +/- 205 to 273 +/- 93 nmol/L by week
      2; P < 0.01). IGFBP-3 levels determined by Western ligand blot were higher during
      the second and third weeks of T administration (265 +/- 28% and 218 +/- 43% of
      control values, respectively; P < 0.05) compared to that at week 0 (165 +/- 44%
      of control values). However, there was no difference in the circulating
      concentration of IGFBP-3, determined by RIA, at weeks 0, 1, 3, and 4 (3.59 +/-
      0.35, 4.00 +/- 0.79, 3.48 +/- 0.56, and 3.65 +/- 0.52 microgram/mL,
      respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7527412
TI  - Effects of pituitary adenylate cyclase-activating polypeptide on hormone
      secretion by human pituitary adenomas in vitro.
AB  - Hormone release in culture in response to pituitary adenylate cyclase-activating
      polypeptide (PACAP) was examined in 28 human pituitary adenomas: 10 null cell
      adenomas, 4 gonadotropin-, 6 GH-, 6 ACTH-, and 2 PRL-producing adenomas. The
      effects of PACAP38 were compared with those of the classical hypothalamic
      releasing hormones and other activators of intracellular signaling pathways.
      PACAP38 significantly stimulated GH release from 1 somatotrope tumor (125 +/- 3%
      of control; P < 0.05) and ACTH release from 3 corticotrope tumors (134 +/- 6%,
      136 +/- 7%, and 137 +/- 9% of control; P < 0.05). The effects of PACAP38 were
      less potent than either GHRH on GH release in the somatotrope tumor or CRH on
      ACTH release in the corticotrope tumors but similar to the responses seen with
      the cAMP analog 8-bromo-cAMP (8-Br-cAMP). No detectable effects of PACAP38 on
      hormone release from null cell, gonadotropin-, or PRL-producing adenomas were
      observed. Of the 5 somatotrope tumors that failed to respond to PACAP38, all also
      failed to respond to either 8-Br-cAMP, TRH, or GHRH. Of the corticotrope tumors
      that failed to respond, 2 of the 3 also failed to respond to CRH. In addition to
      eliciting hormone release appropriate to the tumor type, PACAP38 also stimulated
      glycoprotein hormone alpha-subunit (alpha SU) release from one somatotrope tumor
      (229 +/- 35% of control, P < 0.01) and one corticotrope tumor (149 +/- 4% of
      control; P < 0.01). This response was not mimicked by 8-Br-cAMP in the
      somatotrope tumor, but in the corticotrope tumor a significant alpha SU release
      was also seen after stimulation with the protein kinase C activator 12-O
      tetradecanoyl-phorbol-13-acetate and 8-Br-cAMP. These results suggest that the
      novel hypothalamic peptide PACAP38 has a modest role in the regulation of GH,
      ACTH, and alpha SU secretion from some human tumourous pituitary corticotropes
      and somatotropes. Further studies are needed to elucidate the intracellular
      signaling pathways that mediate the effects of PACAP on hormone secretion by
      these tumor types.

PMID- 7527411
TI  - The insulin-like growth factor-binding protein-4 (IGFBP-4)-IGFBP-4 protease
      system in normal human osteoblast-like cells: regulation by transforming growth
      factor-beta.
AB  - Insulin-like growth factor-binding protein-4 (IGFBP-4) is secreted by normal
      human osteoblast-like (hOB) cells and acts as a potent inhibitor of IGF action.
      hOB cells also secrete a protease, which requires IGFs for activation and
      specifically cleaves IGFBP-4. To study the regulation of this IGFBP-4 protease,
      hOB cells from 26 different adult donors were cultured in serum-free medium for
      24 h in the absence or presence of hormones and other factors known to regulate
      bone growth. hOB cell-conditioned medium (hOB-CM) was collected for measurement
      of IGFBP-4 protease activity in a cell-free assay. This assay involved incubation
      of hOB-CM (50 microL) without or with IGF-II at 37 C for 6 h. IGF-II-activated
      IGFBP-4 hydrolysis was assessed by Western ligand blotting and quantitated using
      laser densitometry. Conditioned medium from all hOB cells examined exhibited
      IGFBP-4 protease activity. PTH, GH, insulin, calcitonin, glucocorticoids, sex
      steroids, 1,25-dihydroxyvitamin D3, and epidermal growth factor had no
      significant effect on IGF-dependent IGFBP-4 protease activity. In comparison, hOB
      CM from cells treated with transforming growth factor-beta (TGF beta) exhibited
      significantly augmented IGF-II-dependent proteolysis of endogenous IGFBP-4.
      Enhanced proteolysis of exogenous IGFBP-4 was also demonstrated: 1) 92% of
      recombinant human IGFBP-4 added to conditioned medium from TGF beta-treated hOB
      cells was hydrolyzed during the assay in the presence of IGF-II compared to 45%
      of recombinant human IGFBP-4 added to control hOB-CM; and 2) increased
      radiolabeled IGFBP-4 fragments were generated in conditioned medium from TGF beta
      treated hOB cells compared with control hOB-CM in the presence of IGF-II. In
      addition to its effect on IGFBP-4 proteolysis, TGF beta treatment decreased IGFBP
      4 messenger ribonucleic acid expression, as measured by Northern analysis. Our
      results indicate that the IGFBP-4-IGFBP-4 protease system in hOB cells can be
      controlled by two of the most abundant local growth factors for bone (IGF-II and
      TGF beta), with each acting via different mechanisms. Regulation of IGFBP-4
      availability may play an important role in the modulation of bone cell
      responsiveness to IGFs.

PMID- 7527413
TI  - A sporadic case of male-limited precocious puberty has the same constitutively
      activating point mutation in luteinizing hormone/choriogonadotropin receptor gene
      as familial cases.
AB  - Familial male-limited precocious puberty (FMPP) is an autosomal dominant disorder
      characterized by marked elevation of serum testosterone despite low levels of
      gonadotropin. Recently, a single point mutation in the LH/hCG receptor (LH/CGR)
      gene was found in FMPP families that constitutively activates the LH/CGR, causing
      Leydig cell activation and precocious puberty. Among the Japanese population,
      only four sporadic cases of male-limited precocious puberty have been reported.
      In the current study, we examined one of the four reported Japanese patients with
      sporadic male-limited precocious puberty and found the same mutation as that in
      the FMPP families. Genomic DNA was isolated, and the polymerase chain reaction
      (PCR) was performed to amplify a fragment of LH/CGR DNA encoding amino acid
      residues that include transmembrane helixes 5 and 6. Sequencing of the PCR
      products revealed a heterozygous adenosine-guanine transition at nucleotide 1733
      in codon 578. The mutation encodes an aspartic acid578-glycine substitution in
      transmembrane helix 6. The mutant LH/CGR, created by site-directed mutagenesis in
      vitro, exhibited constitutively higher cAMP levels in transfected COS-7 cells
      than the wild-type LH/CGR, as described previously; however, basal inositol
      phosphate levels were not increased by transfection with complementary DNA for
      the mutant receptor. The concentration and affinity of [125I]hCG-binding sites
      were similar in cells transfected with the mutant and wild-type LH/CGR
      complementary DNAs, indicating that the mutant did not alter the production of
      receptor or its ability to bind human LH/CG. The sporadic occurrence of this case
      was confirmed by further studies. The mutation creates a recognition site for the
      restriction endonuclease MspI. Restriction digestion was positive for the mutant
      not digested by MspI, indicating that the patient's mutant allele was not
      inherited from his parents. DNA analysis of the patient and the parents, using
      microsatellite repeat markers, was compatible with biological paternity and
      maternity. We conclude that the aspartic acid578-->glycine mutation in the LH/CGR
      has arisen in the Japanese population and is the cause of a sporadic case of male
      limited precocious puberty.

PMID- 7527414
TI  - Characterization of insulin-like growth factor-binding proteins produced by
      cultured fibroblasts from patients with noninsulin-dependent diabetes mellitus,
      insulin-dependent diabetes mellitus, or obesity.
AB  - To evaluate whether the production of insulin-like growth factor-binding proteins
      (IGFBPs) is altered in various pathological states due to modification of the
      hormonal milieu, we analyzed patterns of IGFBPs released into conditioned medium
      during 48-h serum-free culture of early passages of human skin fibroblasts from
      control subjects and patients with metabolic disorders. IGFBP-2, -3, -4, and -5
      were identified in the conditioned medium by immunoblotting or RIA. Compared with
      those in eight control subjects by ligand blot analysis, the levels of IGFBP-3, 
      2, and -5 were reduced to 43%, 47%, and 53% in 10 noninsulin-dependent diabetic
      patients, respectively, whereas the levels of IGFBP-3 and -2 were reduced to 36%
      and 23%, respectively, in 3 nondiabetic obese patients with impaired glucose
      tolerance. In 2 insulin-dependent diabetic patients, the level of IGFBP-3 was
      reduced by 25% and 40%, respectively, and IGFBP-2 was not detectable. In
      contrast, a similar level of IGFBP-4 was detected in both normal and patient's
      conditioned media, except in 1 insulin-dependent diabetic patient. These data
      indicate that fibroblasts derived from patients with metabolic disorders retain
      their intrinsic characteristics even after they are removed from their in vivo
      hormonal milieu.

PMID- 7527415
TI  - Endothelin expression in normal human anterior pituitaries and pituitary
      adenomas.
AB  - Endothelins (ETs) are important regulators of growth and function in many
      endocrine tissues. This study was designed to verify the expression of ETs in a
      series of normal human pituitaries and pituitary adenomas. We examined 13 normal
      pituitaries and 58 pituitary adenomas for the presence of immunoreactive (ir) ET
      1 and ET-3. No ir-ET-1 was detected in any of the 13 normal pituitaries, whereas
      ir-ET-3 was observed in 4 of 13 (31%) cases. In contrast, 48% (28 of 58) of
      pituitary adenomas display immunoreactivity for ET-1, whereas 31% (18 of 58) show
      immunoreactivity for ET-3. With respect to the type of tumors, staining was as
      follows: nonfunctioning adenomas: ET-1, 14 of 33; ET-3, 9 of 33;
      somatotropinomas: ET-1, 8 of 16; ET-3, 6 of 16; corticotropinomas: ET-1, 5 of 5;
      ET-3, 2 of 5; and prolactinomas; ET-1, 1 of 4; ET-3, 1 of 4. Using double
      immunostaining, we found the colocalization of ET-3 in normal pituitaries and of
      ET-1 and ET-3 in pituitaries adenomas in each hormone-secreting cell. In Cushing
      adenomas, ET-1 was coexpressed in corticotropic cells in all 5 cases (100%). In
      the same tumors, by reverse transcriptase polymerase chain reaction, we
      investigated the presence of ET-1 and ET-3 messenger ribonucleic acids and found
      that they are expressed, respectively, in 18 of 21 and 7 of 11 tumors examined.
      Our findings demonstrate that pituitary adenomas frequently display ET-1 as well
      as ET-3 immunoreactivity, in contrast to normal pituitaries, in which only ET-3
      was found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527416
TI  - Differential cellular synthesis of insulin-like growth factor binding protein-1
      (IGFBP-1) and IGFBP-3 within human liver.
AB  - The two major insulin-like growth factor-binding protein (IGFBP) species in the
      human circulation, IGFBP-1 and IGFBP-3, are synthesized in large amounts by
      liver. To determine which hepatic cell populations in human liver were
      responsible for the synthesis and release of these IGFBPs, we 1) performed in
      situ hybridization with specific complementary RNA (RNA) probes for human IGFBP-1
      or-3 or performed immunohistochemical analysis to reveal the sites of messenger
      RNA (mRNA) presence and peptide translation, respectively, in sections of normal
      liver derived from organ donors; and 2) examined the release of IGFBP species by
      Western ligand and immunoblots of medium conditioned by isolated cultures of
      hepatocytes, lipocytes, and Kupffer cells. In situ hybridization showed that
      IGFBP-1 mRNA was distributed widely among the parenchymal cell population, which
      also showed immunohistochemical staining for IGFBP-1 peptide. Conversely, IGFBP-3
      mRNA and immunoreactive peptide were mainly localized to Kupffer cells, which
      were positively identified by immunoreactivity with antiserum against the
      glycoprotein marker, CD68. Isolated hepatocytes released two species of IGFBP of
      28 and 30-32 kilodaltons, which were recognized immunologically as IGFBP-1.
      Isolated Kupffer cells released only a 43- to 46-kilodalton IGFBP immunologically
      recognized as IGFBP-3. Lipocyte cultures released no detectable IGFBP species.
      The results suggest that IGFBP-1 and IGFBP-3 are derived from separate cell
      populations in human liver.

PMID- 7527418
TI  - Changes in circulating insulin-like growth factor-binding protein-1 (IGFBP-1)
      during prolonged exercise: effect of carbohydrate feeding.
AB  - Plasma levels of glucose, insulin, the insulin-like growth factor (IGF-I and -II)
      and IGFBP-1 were determined in four young healthy males performing cycle exercise
      to fatigue while being fed either placebo (trial C) or glucose polymer solution
      (trial G). There was a significant decline in glucose and insulin from rest to
      fatigue in C (P < 0.01 and P < 0.05, respectively), but not in G. IGF-I or IGF-II
      levels did not change significantly in either of the trials. IGFBP-1 levels
      increased 12-fold in C (11.4 +/- 1.6 ng/ml at rest to 136.5 +/- 19.7 ng/ml at
      fatigue P < 0.01), and 5.6-fold in G (11.0 +/- 2.3 ng/ml to 62.2 +/- 15 ng/ml, P
      < 0.05). In C a significant negative correlation was found between IGFBP-1 and
      glucose (r = 0.69, P < 0.01) and IGFBP-1 and insulin (r = -0.612, P < 0.05) in C,
      but not in G. These results suggest that during prolonged exercise factors other
      than insulin or glucose may regulate IGFBP-1 and that IGFBP-1 may serve a role
      other than to prevent the hypoglycaemic action of the IGFs.

PMID- 7527419
TI  - An immunohistochemical study of the vascularization of the human Graafian
      follicle.
AB  - The wall of the largest Graafian follicle or corpus luteum was biopsied in 22
      patients at laparoscopy. Both granulosa and theca cells were contained in 18
      samples. These samples were classified as pre-luteinizing hormone (LH) surge (n =
      3), LH surge (n = 3), early luteal (n = 3), mid-luteal (n = 4), late luteal (n =
      3) and menstrual (n = 2). A double-staining immunohistochemical protocol was used
      to demonstrate proliferating endothelial cells: mouse-anti-rat-proliferating cell
      nuclear antigen, for proliferating cells; mouse-anti-human-CD34 antibody for
      endothelial cells. The percentage of endothelial cells proliferating
      (proliferation index) and the area of tissue occupied by endothelial cells (areal
      fraction) were determined for granulosa and theca layers. Intra- and inter-slide
      coefficients of variation were < 15%. The granulosa layer was avascular until the
      LH surge subsided. Maximum vascularization was achieved by the mid-luteal phase.
      The theca endothelial cell proliferation index was constant from pre-LH surge to
      mid-luteal phases. The mean theca endothelial cell proliferation index for these
      phases was significantly greater than for the late luteal and menstrual phases.
      From first appearance in the granulosa layer, endothelial cells had the same
      proliferation index as the theca endothelial cells, the proliferation index
      decreasing significantly in both after the mid-luteal phase (P = 0.018). It is
      concluded that endothelial cell proliferation is unchanged throughout the
      follicular, early and mid-luteal phases, decreasing significantly in the late
      luteal phase. By contrast, endothelial cell invasion of the membrane granulosa,
      presumably in response to a chemotactic stimulus, occurs after the LH surge has
      subsided.

PMID- 7527420
TI  - The influence of ovarian follicular activity on late proliferative phase serum
      IGFBP-1 in down-regulated assisted conception cycles.
AB  - Serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations were
      measured at the end of the proliferative phase in infertility patients undergoing
      normal menstrual cycle frozen embryo transfer, exogenous hormone-supported frozen
      embryo transfer and in-vitro fertilization (IVF) treatment cycles. These patients
      were divided into five groups according to their ovarian follicular activity. The
      exogenous hormone-supported frozen embryo transfer group, who had no ovarian
      follicles, and the IVF groups (number of follicles ranging from 4-38) showed
      statistically higher serum IGFBP-1 concentrations when compared to the normal
      menstrual cycle group (P < or = 0.01). There was no significant difference in the
      serum IGFBP-1 concentrations between the exogenous hormone support frozen embryo
      transfer group and the poor or normal response IVF groups (number of follicles
      ranging from 4 to 16). An IVF group that displayed an excessive response to our
      standard human menopausal gonadotrophin stimulation (> 20 mature follicles or
      oestradiol > 10,000 pmol/l) showed a significantly higher serum IGFBP-1
      concentration when compared with the other groups (P = 0.001). This subgroup was
      subsequently given a modified (follicle-stimulating hormone) stimulation regime
      which resulted in a significant reduction in serum IGFBP-1 concentrations (P <
      0.05). There was no correlation between serum oestradiol and IGFBP-1 overall or
      within the patient groups. We conclude that serum IGFBP-1 concentrations in our
      down-regulated assisted conception cycles did not increase in line with ovarian
      follicular activity, unless an excessive response was displayed.

PMID- 7527417
TI  - Immunoblot studies of the IGF-related acid-labile subunit.
AB  - Insulin-like growth factors I and II (IGF-I and II) are present in serum
      primarily within a ternary complex consisting of IGF, IGF-binding protein-3 (IGF
      3) and acid-labile subunit (ALS). Relatively little is known about ALS as
      compared to the other components of the complex. We report immunoblot studies of
      ALS using a new rabbit antiserum to human ALS1-34. The antiserum shows high
      specificity for ALS, labelling only the intact 82-88 kDa doublet in whole serum.
      Treatment with endoglycosidase-F leads to only a partial deglycosylation of ALS
      in whole serum, while purified ALS is reduced to M(r) approximately 58 kDa.
      Acidification of both whole serum and purified ALS leads to a complete loss of
      ALS ability to bind to cross-linked IGFBP-3:[125I]IGF-II tracer; however,
      immunoblot studies show no change in the apparent M(r) of the major ALS band.
      Immunoblot studies of human serum shows that intact ALS is decreased in growth
      hormone (GH) deficiency, increases with GH treatment, is elevated in GH excess
      and is unchanged with IGF-I treatment. These data provide new information
      regarding the characteristics of ALS and demonstrate the research utility of a
      highly-specific antiserum for this protein.

PMID- 7527422
TI  - The target antigen for GDA-J/F3 monoclonal antibody in the human sperm tail
      fibrous sheath is a non-collagenous asialo-glycoprotein: implications and
      significance.
AB  - Enzymes and chemicals were used to analyse the biochemical structure of the
      antigenic epitope recognized by GDA-J/F3 monoclonal antibody (MoAb) in the human
      sperm tail fibrous sheath. Treatment of sperm dried onto slides with trypsin or
      dispase enzymes abolished their immunofluorescence staining with GDA-J/F3 MoAb,
      thus indicating the proteinaceous nature of the antigen. The proteolytic cleavage
      of GDA-J/F3 protein by trypsin, which also caused sperm decapitation, indicated
      the presence of peptide bonds involving the carboxyl groups of the basic amino
      acids, arginine and/or lysine. The epitope was also glycosylated as demonstrated
      by its sensitivity to sodium metaperiodate treatment which was dose-dependent.
      The GDA-J/F3 antigenic epitope lacked sialic acid since pre-treatment of
      spermatozoa with sialidase enzyme (neuraminidase) had no effect on their
      reactivity with the antibody. The lack of collagenous domains in the GDA-J/F3
      antigen was demonstrated by the failure of collagenase to abrogate sperm
      immunostaining with the MoAb. Furthermore, type VII collagen of the skin basement
      membrane (BM) was previously thought of as a potential target antigen for GDA
      J/F3 MoAb. This was ruled out since several monoclonal and polyclonal antibodies
      failed to detect the antigen in the spermatozoa using immunofluorescence and
      Western blotting. These data, therefore, show that the target antigen for GDA
      J/F3 MoAb is a non-collagenous asialo-glycoprotein, and by inference provide the
      first evidence for the glycosylation of the sheath proteins as another step of
      post-translational modification occurring during sperm tail development.

PMID- 7527421
TI  - Insulin-like growth factor binding proteins in serum and follicular fluid from
      women undergoing ovarian stimulation with and without growth hormone.
AB  - The effects of supplementary growth hormone (GH) upon insulin-like growth factor
      binding proteins (IGFBP) in serum and ovarian follicular fluid were investigated
      in women undergoing buserelin-human menopausal gonadotrophin (HMG) ovulation
      induction for in-vitro fertilization. IGFBPs were detected by Western ligand
      blotting (WLB) or radioimmunoassay (IGFBP-3) and were shown in the present study
      to increase and decrease in patients with diseases of GH excess or deficiency. In
      the women undergoing treatment for ovulation induction, radioimmunoassay of IGFBP
      3 gave results which were consistent with the well-documented GH dependency of
      this protein, increasing in the serum when GH was administered at the same time
      as buserelin-HMG. In contrast there were no consistent patterns in the abundance
      of the IGFBPs in serum and follicular fluid examined by WLB whether or not the
      patient was receiving GH, and the IGFBPs varied independently of the result
      obtained by radioimmunoassay. Other studies have shown that during pregnancy a
      serum protease can dramatically decrease the detection of the IGFBPs on the WLB.
      However, there was no evidence for a protease in the serum or follicular fluid
      from these nonpregnant women undergoing ovulation induction. Tissue availability
      of IGFs is probably regulated by the BPs, so that data would suggest that in
      normal women, neither ovarian activity nor GH at pharmacological concentrations
      is the primary regulator of the IGFBPs, which are likely to be regulated by some
      other factor(s), e.g. nutrition. These data may account for the lack of
      consistent clinical improvement in studies investigating the hypothesis that
      supplementary GH during ovulation induction with gonadotrophins would be
      beneficial.

PMID- 7527423
TI  - A fucose-containing epitope potentially involved in gamete interaction on the
      human zona pellucida.
AB  - The oligosaccharide moiety of human, porcine and bovine zonae pellucidae was
      studied with lectins and monoclonal antibodies specific for tri- or tetra
      saccharidic epitopes containing at least one terminal alpha-L-fucose. Animal eggs
      were collected from follicular aspirates, human eggs were collected from in-vitro
      fertilization and embryo transfer programmes and pooled into six groups. By
      direct immunofluorescence, the lectins reactivity was detected for the animal or
      the human zonae pools in the same way. Reactivity of Aleuria aurantia lectin
      demonstrated the presence of alpha-L-fucose terminal residues in the zonae from
      the three species studied. By indirect immunofluorescence, the 2-25 antibody
      reactivity was detected in every pool of human zonae whereas there was no
      evidence of any antibody reactivity on animal zonae. Using an anti-Lewis-b blood
      group antibody (2-25), we observed expression of this antigen as an intrinsic
      component of the human zona pellucida, independently of patients' Lewis red blood
      cell phenotypes. Antibody 2-25 inhibited the spermatozoa-zona binding in a
      hemizona assay, suggesting that this fucose-containing antigen could be part of a
      sperm-zona receptor.

PMID- 7527424
TI  - Predictive value of human chorionic gonadotrophin in the outcome of early
      pregnancy after in-vitro fertilization and spontaneous conception.
AB  - This prospective study analyses the value of the beta-subunit of human chorionic
      gonadotrophin (beta-HCG) in 120 pregnancies obtained after in-vitro fertilization
      (IVF)--embryo transfer. Spontaneous conception cycles (n = 16) were also analysed
      allowing a comparison between these two forms of conception. Of the 120 clinical
      pregnancies, 48 started as single gestations and 50 started with two or more
      sacs. There were 14 clinical abortions and eight ectopic pregnancies. All
      subjects had blood samples taken under a fixed protocol on days 11, 14, 17, 20
      and 23 after follicular aspiration. Weekly samples were obtained thereafter until
      day 60 from ovum retrieval. Transvaginal ultrasounds were performed at weekly
      intervals, starting on day 23 after follicular aspiration. In spontaneous
      conception cycles blood samples were obtained daily, starting on the day of
      follicular rupture. In spontaneous conception cycles and in IVF-embryo transfer
      conceptions, the doubling time (DT) of beta-HCG was 1.4 +/- 0.3 and 1.6 +/- 0.4
      days respectively. This difference was not significant. In multigestations, the
      DT was 1.5 +/- 0.3 days. The absolute values of beta-HCG in early spontaneous
      gestations were significantly higher than in IVF-embryo transfer cycles,
      suggesting that the blastocyst implants with less cellular mass when initiated in
      vitro as compared with the in-vivo condition. The early prediction of ectopic
      pregnancy and spontaneous clinical abortion was analysed by the beta-HCG profile
      as well as the absolute values in comparison to normal pregnancies. Both
      parameters showed significant differences as early as the interval between days
      11 and 23 from follicular aspiration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527427
TI  - Comparison of cord blood and peripheral blood mononuclear cells as targets for
      viral isolation and drug sensitivity studies involving human immunodeficiency
      virus type 1.
AB  - We have shown that umbilical cord blood mononuclear cells (CBMC) are at least as
      sensitive as peripheral blood mononuclear cells (PBMC) for isolation of human
      immunodeficiency virus type 1 from the PBMC of infected individuals. Viral
      replication was more efficiently monitored by a p24 antigen capture assay than by
      a viral reverse transcriptase test, regardless of whether CBMC or PBMC were
      employed. We also found that CBMC and PBMC yielded similar results with regard to
      the susceptibility profiles of both wild-type and drug-resistant variants of
      human immunodeficiency virus type 1 for 3'-azido-3'-deoxythymidine, 2',3'
      dideoxycytidine, and the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine.
      Finally, viruses isolated on CBMC could be routinely grown on PBMC and vice
      versa.

PMID- 7527426
TI  - Quantitation of hepatitis C virus genome molecules in plasma samples.
AB  - A competitive reverse transcription PCR (cRT-PCR)-based assay for the
      quantitative detection of hepatitis C virus (HCV) viremia was developed,
      optimized, and applied to the direct molecular analysis of clinical samples from
      nine patients with persistent HCV infection. As for other competitive PCR-based
      applications, this method consists of the reverse transcription and subsequent
      amplification of two RNA species in the same tube: the wild-type template (to be
      quantified) and a known amount of a modified synthetic template. These templates
      have identical primer recognition sites and very similar (but not identical)
      sizes, thus allowing direct detection of both template species after gel
      electrophoresis and ethidium bromide staining. The results obtained by this cRT
      PCR application for testing clinical samples from HCV-infected patients mainly
      indicate that the competitive approach reaches the degree of sensitivity (fewer
      than 5 HCV RNA molecules per 100 microliters) necessary to evaluate viral load in
      all HCV-infected patients, independently of clinical conditions, and that this
      technique is flexible enough to quantify highly divergent levels of cell-free HCV
      genome copy numbers in biological samples. Interestingly, we observed a sample-to
      sample variation in the loss of detectable HCV genome molecules in serum in
      comparison with that in plasma from the same patient, thus indicating that serum
      specimens, although widely used in the past few years for qualitative molecular
      investigation of HCV-infected patients, cannot be used to obtain reliable
      quantitative data on HCV viremia from these patients.

PMID- 7527425
TI  - Differentiation between human immunodeficiency virus type 1 (HIV-1) and HIV-2
      isolates by nonradioisotopic reverse transcriptase-typing assay.
AB  - We tested whether human immunodeficiency virus type 1 (HIV-1) could be
      differentiated from HIV-2 by a reverse transcriptase (RT)-typing assay that
      measured the reduction of enzyme activity owing to specific antibody. RT
      inhibiting antibody was examined for HIV type specificity by a new
      nonradioisotopic RT assay. Antibodies from four rabbits immunized with
      recombinant HIV-1 RT and from 23 HIV-1-seropositive individuals all specifically
      inhibited the enzyme activities of two HIV-1 strains (LAV-1 and GH-3), three
      zidovudine-resistant HIV-1 mutants, and a recombinant HIV-1 RT. However, none of
      these antisera affected the activities of six HIV-2 strains (GH-1, GH-2, GH-4, GH
      5, GH-6, LAV-2ROD), Rous-associated virus type 2, and DNA polymerase I from
      Escherichia coli. In contrast, HIV-2 antibody from a rabbit immunized with
      disrupted GH-1 virions blocked the enzyme activities of the six HIV-2 strains but
      not those of the three HIV-1 strains, Rous-associated virus type 2, or DNA
      polymerase I. These results indicate that the antigenic domains of HIV-1 and HIV
      2 RTs recognized by their inhibiting antibodies are distinct from each other and
      are highly conserved. Clinical HIV isolates from 18 HIV-1-seropositive
      individuals and 3 HIV-2-seropositive Ghanaian individuals were identified as HIV
      1 and HIV-2, respectively, by the nonradioisotopic RT-typing assay.

PMID- 7527430
TI  - Cationic protein-induced sensory nerve activation: role of substance P in airway
      hyperresponsiveness and plasma protein extravasation.
AB  - We have previously reported that human eosinophil granule major basic protein and
      synthetic cationic proteins such as poly-L-arginine and poly-L-lysine, can
      increase airway responsiveness in vivo. In the present study, we have
      investigated whether activation of sensory C-fibers is important in this
      phenomenon. Dose-response curves to methacholine were constructed before and 1 h
      after intratracheal instillation of poly-L-lysine in anaesthetized spontaneously
      breathing rats, and the concentration of methacholine required to induce a
      doubling in total lung resistance was calculated. Poly-L-lysine induced a
      fivefold increase in airway responsiveness, which was inhibited by neonatal
      capsaicin treatment and potentiated by phosphoramidon (100 micrograms/ml).
      Furthermore, pretreatment with either CP, 96-345, or RP-67580 two selective NK-1
      receptor antagonists inhibited poly-L-lysine-induced airway hyperresponsiveness
      and plasma protein extravasation. In vitro, cationic proteins stimulated the
      release of calcitonin gene-related peptide-like immunoreactivity from perfused
      slices of the main bronchi. Our results demonstrate that cationic proteins can
      activate sensory C-fibers in the airways, an effect which is important in the
      subsequent development of airway hyperresponsiveness and plasma protein
      extravasation. Cationic proteins may therefore function as a link between
      inflammatory cell accumulation and sensory nerve activation.

PMID- 7527429
TI  - Changes in pulmonary vascular tone during exercise. Effects of nitric oxide (NO)
      synthase inhibition, L-arginine infusion, and NO inhalation.
AB  - Nitric oxide (NO) is a potent endogenous vasodilator. Its role in the normal and
      stressed pulmonary circulation is unclear. To better understand the importance of
      endogenous NO in normal physiological responses, we studied the effects of
      altered NO availability on the change in pulmonary vascular tone that accompanies
      exercise. In paired studies we measured blood flow and pressures in the pulmonary
      circulation at rest and during treadmill exercise at a speed of 4 mph with and
      without (a) N omega-nitro-L-arginine, 20 mg/kg intravenously, a selective
      inhibitor of NO synthase; (b) L-arginine, 200 mg/kg intravenously, substrate for
      NO synthase; (c) combination of the inhibitor and substrate; and (d) inhalation
      of NO > 30 ppm, to determine if endogenous release of NO elicits maximal
      vasodilation. In addition, we sought to determine the site of NO effect in the
      pulmonary circulation by preconstriction with either U-44619 or hypoxia (fraction
      of inspired O2 = 0.12) using a distal wedged pulmonary catheter technique. NO
      synthase inhibition raised pulmonary vascular tone equally at rest and exercise.
      L-Arginine reversed the effects of NO synthase inhibition but had no independent
      effect. NO inhalation did not reduce pulmonary vascular tone at rest or enhance
      the usual reduction in pulmonary vascular resistance with exercise. The effect of
      NO synthase inhibition was in pulmonary vessels upstream from small veins,
      suggesting that endogenous NO dilates primarily small arteries and veins at rest.
      We conclude that, in sheep, endogenous NO has a basal vasodilator function that
      persists during, but is not enhanced by, exercise.

PMID- 7527431
TI  - Gadolinium inhibits mechanoelectrical transduction in rabbit carotid
      baroreceptors. Implication of stretch-activated channels.
AB  - Gadolinium (Gd3+) has been shown to prevent mechanoelectrical transduction
      believed to be mediated through stretch-activated channels. We investigated the
      possible role of Gd(3+)-sensitive channels in mediating baroreceptor activity in
      the carotid sinus of rabbits. Baroreceptor activity induced by a ramp increase of
      carotid sinus pressure was reduced significantly during exposure to Gd3+. The
      inhibition was dose-related and reversible, and was not associated with
      alteration of carotid sinus wall mechanics as the pressure-strain relationship
      was unaffected. Veratrine triggered action potentials from single- and multiple
      baroreceptor fibers when their response to pressure was inhibited by Gd3+. This
      suggests that the effect of Gd3+ on baroreceptors in the isolated carotid sinus
      was specific to their mechanical activation. The results suggest that stretch
      activated ion channels sensitive to Gd3+ may be the mechanoelectrical transducers
      of rabbit carotid sinus baroreceptors.

PMID- 7527432
TI  - A two-step adhesion cascade for T cell/endothelial cell interactions under flow
      conditions.
AB  - Neutrophil adherence to endothelial cells (ECs) under conditions of flow occurs
      in successive steps, including selectin-dependent primary adhesion and CD18
      dependent secondary adhesion. We used a parallel-plate flow chamber to assess the
      steps in T cell adherence in vitro. On monolayers of L cells transfected with the
      EC adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1), or
      intercellular adhesion molecule-1 (ICAM-1), E-selectin was capable of mediating
      only primary adhesion, ICAM-1 was capable of mediating only secondary adhesion,
      and VCAM-1 was capable of mediating both primary and secondary adhesion. Studies
      using human umbilical vein EC monolayers stimulated for 24 h with IL-1 also
      revealed distinct primary and secondary steps in T cell adhesion under flow, and
      the secondary adhesion was inhibited > 90% by blocking both VCAM-1/alpha 4 beta 1
      integrin and ICAM-1/CD18 integrin pathways. However, the primary adhesion under
      conditions of flow could not be attributed to any of the mechanisms known to
      support adhesion of leukocytes to ECs. Alone, this pathway was shown to mediate T
      cell rolling and was a necessary prerequisite for engagement of the two integrin
      pathways in this system. Thus, T cell adherence to 24-h IL-1-stimulated human
      umbilical vein ECs at venular wall shear stresses involves at least two
      successive steps, with clear molecular distinctions from the mechanisms
      accounting for neutrophil/EC adhesion.

PMID- 7527428
TI  - Endothelial nitric oxide synthase is expressed in cultured human bronchiolar
      epithelium.
AB  - Nitric oxide (NO) is an important mediator of physiologic and inflammatory
      processes in the lung. To better understand the role of NO in the airway, we
      examined constitutive NO synthase (NOS) gene expression and function in NCI-H441
      human bronchiolar epithelial cells, which are believed to be of Clara cell
      lineage. NOS activity was detected by [3H]arginine to [3H]citrulline conversion
      (1,070 +/- 260 fmol/mg protein per minute); enzyme activity was inhibited 91% by
      EGTA, consistent with the expression of a calcium-dependent NOS isoform.
      Immunoblot analyses with antisera directed against neuronal, inducible, or
      endothelial NOS revealed expression solely of endothelial NOS protein.
      Immunocytochemistry for endothelial NOS revealed staining predominantly in the
      cell periphery, consistent with the association of this isoform with the cellular
      membrane. To definitively identify the NOS isoform expressed in H441 cells, NOS
      cDNA was obtained by degenerate PCR. Sequencing of the H441 NOS cDNA revealed
      100% identity with human endothelial NOS at the amino acid level. Furthermore,
      the H441 NOS cDNA hybridized to a single 4.7-kb mRNA species in poly(A)+ RNA
      isolated from H441 cells, from rat, sheep, and pig lung, and from ovine
      endothelial cells, coinciding with the predicted size of 4.7 kb for endothelial
      NOS mRNA. Guanylyl cyclase activity in H441 cells, assessed by measuring cGMP
      accumulation, rose 6.6- and 5.4-fold with calcium-mediated activation of NOS by
      thapsigargin and A23187, respectively. These findings indicate that endothelial
      NOS is expressed in select bronchiolar epithelial cells, where it may have
      autocrine effects through activation of guanylyl cyclase. Based on these
      observations and the previous identification of endothelial NOS in a kidney
      epithelial cell line, it is postulated that endothelial NOS may be expressed in
      unique subsets of epithelial cells in a variety of organs, serving to modulate
      ion flux and/or secretory function.

PMID- 7527433
TI  - Epithelial expression of HLA class II antigens and Fc gamma receptors in patients
      with adult periodontitis.
AB  - The distribution of HLA class II (DR, DP, DQ) and Fc gamma R (I, II, III) was
      analyzed in the epithelia of patients with advanced marginal periodontitis using
      cryostat sections incubated with monoclonal antibodies (MoAb) against the
      Langerhans cell (LC) (CD1a) and various subtypes of HLA class II and Fc gamma R,
      and the indirect immunofluorescence technique. In the oral gingival epithelium
      (OGE), LC were concentrated subjacent to the connective tissue papillae, while in
      the pocket epithelium (PE), they were most abundant at the gingival margin. HLA
      DP, DQ, and DR stained LC in both OGE and PE. HLA-DQ+ LC were significantly fewer
      than DP+ and DR+ LC. HLA-DR also stained keratinocytes (KC) in the whole
      extension of both OGE and PE. HLA-DP was also observed on KC, but not HLA-DQ. Fc
      gamma R II stained both LC and focal areas of KC. In PE FC gamma R II+ LC were
      concentrated near the bottom of the pocket, while in the OGE, they were
      concentrated at the gingival margin. Fc gamma R III was present only on KC,
      especially in the basal and suprabasal layer. The results indicate that the
      epithelial cells are actively involved in the development and maintenance of the
      inflammation of periodontal disease.

PMID- 7527434
TI  - The effect of deoxynivalenol on serotoninergic neurotransmitter levels in pig
      blood.
AB  - Deoxynivalenol (DON) produces two characteristic toxicological effects, decreased
      feed consumption (anorexia) and emesis. Both effects have been linked to
      increased central (CNS) serotoninergic activity. Although there has also been
      some indication of a peripheral involvement, the role of blood pools of serotonin
      and related compounds in mediating DON toxicity is not well defined. In this
      study, the effect of DON on plasma concentrations of serotonin (5
      hydroxytryptamine, 5HT), 5HIAA (5-hydroxyindoleacetic acid) and tryptophan (TRP),
      as a reflection of an induced peripheral serotoninergic system, was investigated
      in swine. Typical values for the plasma concentrations of 5HT, 5HIAA, and TRP
      were established in pigs. Following administration of DON, either
      intragastrically or intravenously, concentration changes in these substances were
      measured over an eight hour period. The effect of low and high toxin doses were
      also compared. Analyses showed no effect on plasma levels of the compounds of
      interest, even at sufficient toxin doses to invoke emesis in the test animals.
      Any variation over the course of the study remained within acceptable control
      limits. These results indicated no peripheral effect by DON which could account
      for the increased serotoninergic activity associated with altered feeding
      behaviour or emesis.

PMID- 7527435
TI  - Coinfection of hepatitis C virus in patients with chronic hepatitis B infection.
AB  - Enzyme-linked immunosorbent assays for detecting antibodies against hepatitis C
      virus and the polymerase chain reaction were tested in 82 chronic hepatitis B
      surface antigen carriers for their accuracy in diagnosing patients coinfected
      with hepatitis B and C viruses. To clarify the role of each virus in chronic
      hepatitis, serologic assays against hepatitis B virus were also tested. Thirteen
      (14.9%), 14 (17.1%) and 15 (18.3%) patients were anti-HCV positive using C100
      (HCV1), JCC, and a second generation test (HCV2), respectively. HCV RNA was
      detected by polymerase chain reaction in 9 of 18 anti-HCV-positive cases.
      Although HCV1 assays were not sufficient, either the JCC or HCV2 assay detected
      all polymerase chain reaction-positive cases. Fifteen of 18 specimens that were
      positive in at least one of the three ELISA were seronegative for the hepatitis B
      e antigen. As judged by HBV DNA polymerase activity, titers of hepatitis B
      surface antigen and immunoglobulin A antibody against hepatitis B core antigen
      (IgA anti-HBc), activity of hepatitis B virus replication and immune response
      against hepatitis B virus in patients with coinfection was decreased to the level
      of hepatitis B virus asymptomatic carriers. These results show that hepatitis C
      virus appears to be the primary cause of active hepatitis in most patients with
      hepatitis B and hepatitis C virus coinfection.

PMID- 7527436
TI  - Protein synthesis in regenerating rat liver during malnutrition.
AB  - To examine the effect of malnutrition on liver protein metabolism and synthesis
      during liver regeneration, 104 rats were allocated to semi-starvation or ordinary
      food intake for 1 week. Half of each group was sham operated and the other half
      was partially hepatectomized. Specimens were taken from the liver at the time of
      liver resection and from animals killed 24, 48 and 72 h after the primary
      operation. Liver samples were analysed for DNA and protein, and in the 48-h
      groups RNA and protein synthesis were also analysed. Protein synthesis was
      measured by the flooding method using L[4-3H] phenylalanine. The liver weight
      during regeneration increased very rapidly in the well-nourished animals, but
      when expressed as percent of body weight or as proportional increases, the
      difference between well-nourished and malnourished animals disappeared. The
      fractional rate of protein synthesis was not changed in sham-operated
      malnourished or well-nourished animals. During regeneration, protein synthesis in
      well-nourished animals was elevated compared to sham-operated controls, but a
      lesser stimulation was seen in malnourished rats. It was concluded that the
      mechanism of liver regeneration depends on nutritional state, involving an
      increase in protein synthesis in well-nourished animals, but relying more on a
      decrease in protein degradation or cessation of secretory protein synthesis in
      malnourished animals.

PMID- 7527438
TI  - Lack of efficacy of inosine pranobex in the treatment of chronic hepatitis C.

PMID- 7527437
TI  - Effect of antiandrogen treatment on chemical hepatocarcinogenesis in rats.
AB  - We studied the effect of antiandrogen treatment on the Solt-Farber model of
      hepatocarcinogenesis in male Sprague-Dawley rats. The size and number of the
      liver tumors were reduced by various antiandrogen treatments (orchiectomy, an LH
      RH analog, and chlormadinone acetate). In addition, the proportion of poorly
      differentiated carcinomas was decreased by the antiandrogen treatment, while that
      of well-differentiated trabecular or glandular carcinomas was increased. The
      bromodeoxyuridine labeling index of the tumor cells was significantly decreased
      after the antiandrogen treatment. The expression of rat androgen receptor mRNA in
      carcinoma tissue was increased when compared to control liver tissue, and was
      decreased after the antiandrogen treatment. Orchiectomy had the greatest
      inhibitory effect on carcinoma, although the effect of chemical orchiectomy using
      an LH-RH analog was almost similar to that of orchiectomy. These results suggest
      that the clinical application of antiandrogen therapy for human hepatocellular
      carcinoma might be possible in the future.

PMID- 7527439
TI  - IL-12 is expressed and released by human keratinocytes and epidermoid carcinoma
      cell lines.
AB  - IL-12 is a 70-kDa heterodimeric cytokine composed of two covalently linked
      chains, p40 and p35. IL-12 has multiple effects on T and NK cells and recently
      was found to be required for optimal Th1 cell development. In a variety of
      inflammatory skin disorders including delayed type hypersensitivity and contact
      hypersensitivity, Th1 cells appear to be critically involved. Because
      keratinocytes are well known to exhibit the capacity to release a variety of
      proinflammatory and immunologic cytokines, and thereby to be able to modulate
      inflammatory and immune reactions within the skin, it was investigated whether
      human keratinocytes and keratinocyte cell lines can release IL-12. Supernatants
      of phorbol-12,13-dibutyrate (PDBu) stimulated human epidermoid carcinoma cell
      lines (KB, A431) induced IFN-gamma production by PBL. This activity could be
      completely blocked by the addition of an anti-IL-12 Ab directed against the p40
      subunit of IL-12 (C8.6). Release of IL-12 by keratinocyte cell lines was further
      confirmed by an RIA specific for p40. Immunoprecipitation under reducing
      conditions using the C8.6 Ab yielded specific bands at 40 kDa in supernatants of
      both KB cells and normal human keratinocytes. Northern blot analysis revealed IL
      12-specific mRNA transcripts in PDBu-treated KB cells using cDNA probes encoding
      for p35 and p40. Moreover, by reverse transcription PCR specific transcripts for
      p35 and p40 were found in keratinocytes. These data indicate that keratinocyte
      cell lines and, although to a much lesser degree, normal human keratinocytes,
      exhibit the capacity to make IL-12; thus demonstrating for the first time IL-12
      production by nonhemopoietic cells. Thus, one may speculate that keratinocytes
      via this capacity may influence the fate of Th-mediated immune responses,
      favoring Th1 responses by enhanced production of IL-12 or Th2 responses by
      reduced IL-12 release.

PMID- 7527441
TI  - Regulation of adhesion molecule expression by CD8 T cells in vivo. II. Expression
      of L-selectin (CD62L) by memory cytolytic T cells responding to minor
      histocompatibility antigens.
AB  - Activation of murine T cells by Ag or mitogens results in changes in the
      expression of several cell-surface adhesion molecules that alter the way in which
      these cells migrate and localize in tissues in vivo. As naive CD8 precursor cells
      in lymph nodes (LN) differentiate into effector CTL in response to a skin
      allograft, they up-regulate their expression of Pgp-1 (CD44), VLA-4, and LFA-1
      (CD11a/18), while down-regulating L-selectin (CD62L). All cytolytic activity is
      therefore present in this minor population of L-selectin- Pgp-1high LN T cells.
      We now report that, late after rejection of minor histocompatibility Ag-disparate
      skin grafts, the majority of memory CD8 T cells express both L-selectin and Pgp-1
      and thus would be expected to migrate via the classical route of recirculation
      through LN. Furthermore, restimulation of these memory cells by Ag causes them to
      down-regulate L-selectin, so that memory-effector cells have the same L-selectin-
      Pgp-1high phenotype as do primary effector cells. These results are in contrast
      to recent reports that murine and ovine CD4 memory cells do not express L
      selectin or recirculate through LN high endothelial venules. In addition,
      although virgin and naive CD4 cells may be divided based upon their expression of
      CD45RA or CD45RB, memory CD8 cells cannot be differentiated by their expression
      of CD45 isoforms.

PMID- 7527442
TI  - Outcome of Kupffer cell antigen presentation to a cloned murine Th1 lymphocyte
      depends on the inducibility of nitric oxide synthase by IFN-gamma.
AB  - The interaction between lymphocytes and the resident hepatic macrophage, the
      Kupffer cell (KC), is relevant to the phenomenon of immune tolerance to Ags
      entering the liver. Tolerance to Ag administered via the portal vein can be
      prevented by the rare earth lanthanide metal, gadolinium (Gd). Therefore, we
      studied the ability of OVA-responsive, H-2d-restricted Th1 clones to proliferate
      in response to KCs from DBA/2J (H-2d) mice that had been injected with either
      saline (control) or a Gd solution. Whereas control KCs functioned as effective
      APCs, KCs from Gd-injected mice (GdKC) were incapable of sustaining the
      proliferative response of the Th1 clone to the 16 mer of OVA (323-339). This lack
      of proliferation was determined not to be caused by impaired Ag processing, but
      rather was the result of IFN-gamma-stimulated nitric oxide (NO) release by the
      APC: 1) In vitro addition of the nitric oxide synthase (NOS) inhibitor NG-methyl
      L-arginine (NMMA) restored the ability of the Gd-treated KC to stimulate clone
      proliferation. 2) Additional of anti-IFN-gamma, but not anti-IL-2 or anti-IL-4,
      prevented the induction of NOS in the Gd-exposed KC and was associated with clone
      proliferation. 3) IFN-gamma levels from clone-GdKC-OVA cocultures closely
      paralleled the nitrite released by GdKCs. 4) Only the addition of rIFN-gamma, and
      not IL-2 or IL-4, to cultures of purified GdKCs resulted in the release of
      nitrite. The results of the study suggest an autocrine loop initiated by the
      interaction of the clone's TCR with the class II MHC molecule presenting
      processed OVA on the surface of KC. This interaction stimulates the Th1
      lymphocyte to release IFN-gamma, which in turn induces NO release by KCs isolated
      from Gd-injected mice. This release of NO blocks Th1 proliferation. Such a
      feedback loop may have particular relevance to Ag-specific tolerance, which is
      not only induced by the administration of Ag into the portal vein, but is also
      prevented by Gd pretreatment of the recipient animal.

PMID- 7527440
TI  - Characterization of a granule-independent lytic mechanism used by CTL hybridomas.
AB  - The mechanism(s) by which CTL induce target cell lysis have not been clearly
      elucidated. Perforin and the cytotoxic cell proteinases (granzymes) contained
      within the granules of CTL and NK, have been implicated, but abundant evidence
      for the existence of alternate lytic pathways has accumulated. In this report we
      characterize the mechanism of killing used by two cytolytic hybridomas (PMM-1 and
      MD90) that express neither perforin nor the granzymes. These characteristics are
      compared with results obtained by using a representative Ag-dependent, granule
      containing T cell clone in cytolysis assays. The major differences were that the
      granule-negative hybridomas could lyse a variety of target cells in the presence
      of cyclosporin and the absence of calcium. All the effectors could kill in the
      presence of protein synthesis inhibitors (cycloheximide and emetine) and induced
      DNA fragmentation in the target cells. The cytolytic hybridomas had to be
      stimulated to be cytolytic and this activation required the presence of calcium,
      was dependent on protein synthesis, and inhibited by the addition of cyclosporin.
      Although TNF was shown not be involved, the sensitivity of the target cells to
      lysis by the granule-negative killers correlated with the level of expression of
      Fas Ag. With the use of L1210 and an L1210 cell line transfected with Fas cDNA we
      demonstrated that these MD90 and PMM-1 kill the latter much more effectively and
      that this increase was effectively inhibited with anti-Fas Ab. Furthermore the
      lack of sensitivity to cyclosporin, cycloheximide, emetine, and EGTA was
      confirmed with these targets. We conclude that these two cytolytic hybridomas use
      the Fas lytic pathway to induce lysis in target cells.

PMID- 7527443
TI  - CD44 is a cytotoxic triggering molecule in human peripheral blood NK cells.
AB  - Previous studies have shown that target cells that bind to CD44 adhesion
      molecules on cloned cytotoxic T cells are lysed by the CTL. To determine whether
      CD44 is also a cytotoxic trigger molecule in human PBL, we tested a bispecific Ab
      consisting of anti-CD44 Fab cross-linked to a Fab against a target cell Ag, in
      cytotoxicity assays using PBL as effectors. We found that PBL mediated lysis in
      the presence of the anti-CD44 bispecific Ab provided that the effector cells were
      stimulated with either IL-2 or IL-12. Cell fractionation experiments showed that
      CD44-directed cytolysis was mediated exclusively by CD56+ low buoyant density
      cells, mainly by NK (CD16+) cells, but also to a lesser extent by CD56+ T cells.
      CD44-directed cytolysis appeared in these subsets 24 to 48 h after addition of IL
      2 and paralleled the acquisition of Ab-independent (LAK) activity; in contrast,
      these cells mediated Ab-dependent cellular cytotoxicity and CD3 redirected lysis
      before stimulation with IL-2. Unstimulated CD56+ cells uniformly expressed high
      levels of CD44 that increased modestly after incubation with IL-2. No changes in
      isoform expression in the extracellular domain of CD44 could be detected upon
      activation with the use of isoform-specific mAbs. Thus, lymphokine stimulation
      caused CD44 to become a cytotoxic trigger in subsets of PBL that mediated other
      forms of cytotoxicity and expressed CD44 before activation, suggesting that
      activation of these cells was accompanied by a coupling of CD44 to their lytic
      machinery.

PMID- 7527444
TI  - The relationship between class I binding affinity and immunogenicity of potential
      cytotoxic T cell epitopes.
AB  - The relationship between binding affinity for HLA class I molecules and
      immunogenicity of discrete peptide epitopes has been analyzed in two different
      experimental approaches. In the first approach, the immunogenicity of potential
      epitopes ranging in MHC binding affinity over a 10,000-fold range was analyzed in
      HLA-A*0201 transgenic mice. In the second approach, the antigenicity of
      approximately 100 different hepatitis B virus (HBV)-derived potential epitopes,
      all carrying A*0201 binding motifs, was assessed by using PBL of acute hepatitis
      patients. In both cases, it was found that an affinity threshold of approximately
      500 nM (preferably 50 nM or less) apparently determines the capacity of a peptide
      epitope to elicit a CTL response. These data correlate well with class I binding
      affinity measurements of either naturally processed peptides or previously
      described T cell epitopes. Taken together, these data have important implications
      for the selection of epitopes for peptide-based vaccines, and also formally
      demonstrate the crucial role of determinant selection in the shaping of T cell
      responses. Because in most (but not all) cases, high affinity peptides seem to be
      immunogenic, our data also suggest that holes in the functional T cell
      repertoire, if they exist, may be relatively rare.

PMID- 7527445
TI  - Cytokeratin peptide SFGSGFGGGY mimics N-acetyl-beta-D-glucosamine in reaction
      with antibodies and lectins, and induces in vivo anti-carbohydrate antibody
      response.
AB  - Recently, we found that human anti-GlcNAc mAbs reacted with keratin from human
      skin and recognized specific peptide epitopes of human cytokeratin 14. Our data
      demonstrate that anti-keratin Ab responses in mice might be driven by Ags bearing
      terminal O-linked GlcNAc residues. To determine if mouse anti-GlcNAc mAbs
      recognized peptide epitopes of keratin, several mouse anti-GlcNAc mAbs were
      reacted with a panel of overlapping synthetic decapeptides of the entire amino
      acid sequence of human cytokeratin 14 in the ELISA. Results of the ELISA
      demonstrated that three mAbs, HGAC 54, HGAC 78, and 101.4.1, expressed maximal
      binding activity to keratin peptide B1 with the amino acid sequence SFGSGFGGGY.
      In addition, we found that mouse anti-cytokeratin 14 mAb CKB-1 recognized the
      same peptide and expressed anti-GlcNAc activity as well. Keratin peptide B1 was
      shown to react not only with anti-GlcNAc mAbs but also with several lectins such
      as wheat germ agglutinin, Datura stramonium lectin, Lycopersicon esculentum
      lectin, Solanum tuberosum lectin, and lectin from Wisteria floribunda. Reaction
      of the lectins with solid-phase keratin peptide B1 was inhibited by soluble
      GlcNAc and was not inhibited by glucose demonstrating specificity of binding.
      Using a panel of 24 synthetic keratin B1 peptides, each with a single amino acid
      substitution, we found that aromatic-aromatic and hydrophobic interactions were
      the major driving forces in the stabilization of the peptide-protein complexes.
      Finally, we demonstrated that immunization of BALB/c mice with peptide B1
      conjugated to BSA induced an anti-GlcNAc Ab response. Results of our experiments
      indicated that certain peptides may express functional activity similar to GlcNAc
      and induce in vivo anti-carbohydrate Ab responses.

PMID- 7527448
TI  - Monoclonal antibodies detect different distribution patterns of IL-8 receptor A
      and IL-8 receptor B on human peripheral blood leukocytes.
AB  - mAbs previously reported to be specific for IL-8R type A (IL-8R-A) and mAbs
      specific for IL-8R type B (IL-8R-B), which are described in this paper, were used
      to investigate the expression of each receptor on various types of cells. We
      generated mAbs specific for IL-8R-B, 4D1, and 10H2 by immunizing mice with 293
      cells that expressed IL-8R-B and by selecting hybridoma cell lines that secreted
      mAbs that bind to human neutrophils. Flow cytometry showed that mAbs 4D1 and 10H2
      were specific for IL-8R-B, as determined by their exclusive binding to 293-27
      cells that expressed IL-8R-B, but not to 293-71 cells that expressed IL-8R-A.
      Epitopes recognized by these IL-8R-B-specific mAbs were shown to be within the N
      terminal residues 1-18 of the IL-8R-B on the basis of their binding to various N
      terminal peptides, as measured by ELISA. These IL-8R-B-specific mAbs were able to
      inhibit up to 90 and 50% of the 125I-labeled IL-8 binding to 293-27 cells and
      human neutrophils, respectively. The combination of mAb 9H1 (anti-IL-8R-A) and
      mAb 10H2 (anti-IL-8R-B) inhibited approximately 70% of 125I-labeled IL-8 binding
      to human neutrophils. Flow cytometry showed a wide range of donor variation in
      the expression levels of IL-8R-A and IL-8R-B on various human peripheral blood
      leukocytes. All neutrophils, all monocytes, and 5 to 25% of total lymphocytes
      (CD8+ T cells and CD56+ NK cells) expressed IL-8R. Neutrophils expressed the
      highest level of both IL-8R-A and IL-8R-B, at an approximately equal ratio,
      whereas monocytes and IL-8R+ lymphocytes expressed higher levels of IL-8R-B than
      IL-8R-A. Double-color flow cytometric analysis showed that 7 to 42% of CD8+ T
      cells and 39 to 76% of CD56+ NK cells, but no CD 20+ B cells or CD4+ T cells,
      expressed IL-8R.

PMID- 7527446
TI  - Construction, expression, and immunogenicity of multiple tandem copies of the
      Schistosoma mansoni peptide 115-131 of the P28 glutathione S-transferase
      expressed as C-terminal fusions to tetanus toxin fragment C in a live aro
      attenuated vaccine strain of Salmonella.
AB  - Genetic fusions have been constructed between the highly immunogenic but atoxic
      fragment C of tetanus toxin and a guest peptide, aa115-131, from the protective
      28-kDa glutathione S-transferase Ag of Schistosoma mansoni. Fusions have been
      assembled to express one, two, four, and eight tandem copies of the peptide. The
      recombinant vectors have been electroporated into the nonvirulent aroA strain of
      Salmonella typhimurium SL3261. The fusion proteins are soluble and stably
      expressed in Salmonella as evaluated by Western blotting with fragment C and
      glutathione S-transferase antisera. Mice have been immunized i.v. with a single
      dose of the live recombinant salmonellae. The strains are stable in mice and
      elicit Ab responses directed against fragment C, as determined by enzyme-linked
      immunosorbent assays. Ab responses were also detected against the guest peptide.
      The Ab responses improved dramatically toward the aa115-131 peptide with
      increasing copy number, with the octameric "repitope" fusion displaying the
      greatest potency. This approach may represent a general strategy for eliciting
      immune responses against peptides in live bacterial vaccines.

PMID- 7527447
TI  - A decapeptide (Gln-Asp-Leu-Thr-Met-Lys-Tyr-Gln-Ile-Phe) from human melanoma is
      recognized by CTL in melanoma patients.
AB  - The decapeptide 810 (QDLTMKYQIF) contains the antigenic epitope (KYQI) recognized
      by human mAb L92. This sequence is found in a 43-kDa protein associated with
      human melanoma M14. We examined the expression of 810 in human cells and its
      involvement in the cellular immune responses of melanoma patients. Nineteen stage
      III melanoma patients and 19 normal donors were studied for their responses to
      810. All patients were immunized in vivo with an allogeneic melanoma cell
      vaccine. PBMC cytotoxicity was tested on autologous EBV-transformed B
      lymphoblastoid cell lines (BCL) pulsed with 810 and autologous melanomas.
      Proliferative responses of PBMC to 810 were evaluated by using [3H]Tdr
      incorporation assays. Western blotting revealed that the 43-kDa protein was not
      specific to melanoma but was common to various cells. However, the percentage of
      cytotoxicity of PBMC against autologous 810-pulsed BCL was significantly greater
      in melanoma patients than in normal controls (p < 0.005). Cytotoxicity was
      increased after melanoma cell vaccine immunization in 15 patients (78%).
      Proliferative responses to 810 were observed only in melanoma patients and were
      enhanced in 12 patients (63%) after vaccination. Restimulation of PBMC from
      vaccinated patients with 810 increased cytotoxicity against both autologous 810
      pulsed BCL and melanomas. These targets were lysed by CD8+ T lymphocytes in an
      HLA class I-restricted manner. HLA-A2 and -A11 seemed to serve as the 810
      presenting molecule. Our findings indicate that 810 may function as an epitope
      for CTL on human melanoma and can be used as a vaccine.

PMID- 7527450
TI  - Immunosuppression to cardiac allografts and soluble antigens by anti-vascular
      cellular adhesion molecule-1 and anti-very late antigen-4 monoclonal antibodies.
AB  - Effective activation of T cells in immune responses depends on two signals, one
      from the CD3/TCR complex and another from accessory cell surface proteins. Very
      late Ag-4 (VLA-4) can exert a costimulatory function upon binding with vascular
      cellular adhesion molecule-1 (VCAM-1). We investigated the effects of mAbs
      against VCAM-1 and VLA-4 on cardiac allograft survival and humoral response to
      soluble Ags. BALB/c hearts were transplanted into C3H/He recipients. mAbs (100
      micrograms/day) were administered i.p. for the first 6 days. Graft survival in
      mice treated with M/K-2 (anti-VCAM-1; median survival: 20 days, n = 6) and those
      treated with PS/2 (anti-VLA-4; 30 days, n = 6) was greater than that in control
      mice (8 days, n = 7). Eight of 18 mice treated with both M/K-2 and PS/2 accepted
      the grafts over 65 days, and five of them accepted the grafts over 100 days.
      Allografts treated with the two mAbs showed scattered infiltration of leukocytes
      without evidence of active rejection at 65 days. Mice with long-surviving cardiac
      grafts were challenged with skin grafts from donor and third-party (C57BL/6)
      strains. Survival of the donor-type skin was significantly greater than that of
      the third-party skin. One mouse specifically accepted the donor-type skin
      indefinitely (> 150 days). FACS analysis of splenocytes at 55 days after
      transplantation showed complete recovery of VLA-4 expression from a down
      regulation observed at day 7. In addition, mice immunized with heat-aggregated
      human gamma-globulin did not produce specific Ab, even after boost immunization,
      if PS/2 was administered at the time of the first immunization. This
      unresponsiveness to xenogeneic protein lasted for more than 50 days. These
      results indicate that in vivo administration of anti-VCAM-1 and anti-VLA-4 mAbs
      induces specific immunosuppression to cardiac allografts and soluble Ags.

PMID- 7527449
TI  - IL-10 is induced during HIV-1 infection and is capable of decreasing viral
      replication in human macrophages.
AB  - IL-10 has been shown to be capable of down-regulating several aspects of
      macrophage function. This study was undertaken to define the association between
      IL-10 and HIV-1 infection in human macrophages. Infection of macrophages with a
      monocytotropic strain of the human immunodeficiency virus, HIV-BaL, resulted in
      expression of IL-10 mRNA within 3 to 12 h after infection, as determined by the
      reverse transcriptase PCR. Biologically active IL-10 was detected in supernatants
      from HIV-1-infected macrophages as early as 12 h post-infection. The addition of
      human rIL-10 to HIV-1-infected macrophage cultures resulted in a significant
      decrease in the viral replication. In addition, exogenous IL-10 blocked the
      ability of TNF-alpha to elevate viral replication. To determine whether IL-10 was
      associated with in vivo infection, lymph nodes from AIDS patients were examined
      for the presence of IL-10 mRNA by using PCR. IL-10 mRNA was evident in all lymph
      node tissue examined, but was absent in normal lymph node biopsies. These in
      vitro and in vivo findings demonstrate a strong and heterogeneous association
      between HIV-1 infection and IL-10.

PMID- 7527451
TI  - Defective T cells from gld mice play a pivotal role in development of Thy
      1.2+B220+ cells and autoimmunity.
AB  - The gld mouse represents a fascinating animal model of autoimmune disease, which
      is characterized by massive development of Thy-1.2+B220+ CD4-CD8- cells. These
      cells thus have double positive markers for T and B cells, but are double
      negative for CD4 and CD8 markers and are thus designated DN cells in the present
      context. An additional important feature in gld mice is a defect in expression of
      Fas ligand. To investigate the regulatory role of bone marrow-derived cells for
      the development of these DN cells and of gld autoimmunity, we constructed
      chimeric mice transplanted with fetal liver cells or fetal thymus from gld mice
      into nonirradiated severe combined immunodeficient (SCID) mice. These chimeric
      mice regenerated, developed both these DN cells and the gld autoimmune syndrome
      and also generalized lymphoproliferative disorders. However, when fetal liver
      cells from both gld and non-gld mice (C57BL/10 Thy-1.1 mice) were co-transplanted
      into SCID mice, the development of DN cells was apparently inhibited. Further,
      this inhibition was also seen in SCID mice that had been grafted with both gld
      and non-gld fetal thymus revealing the pivotal role played by T cells in
      development of DN cells. When B cells purified from non-gld (C3H+/+) mice were
      transplanted into SCID mice grafted with gld fetal thymus, the development of DN
      cells was not inhibited. Taken together, these findings indicate that T cells
      from non-gld mice inhibit the expression of gld features, e.g.,
      lymphoproliferation, immune-based nephritic disease, and autoantibody production.
      These findings also suggest that the Fas ligand is selectively expressed on T
      cells.

PMID- 7527453
TI  - Comparison of autologous bone marrow transplantation with sequential chemotherapy
      for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete
      remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte.
AB  - PURPOSE: Intensive chemotherapy followed by autotransplantation has given
      promising results in partially responding or sensitive relapsed patients with
      aggressive non-Hodgkin's lymphoma. In 1987, we designed a randomized study to
      evaluate the potential benefit of a high-dose regimen containing
      cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation
      over a consolidative sequential chemotherapy (ifosfamide, etoposide,
      asparaginase, and cytarabine) in patients in first complete remission with
      intermediate- and high-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS:
      Patients were younger than 55 years and had at least one adverse prognostic
      factor. Induction treatment was that of the LNH84 protocol with an open
      randomization on the anthracycline. Patients in complete remission were further
      randomly assigned to receive either consolidation procedure. RESULTS: After
      induction treatment, 464 patients were assessable for the consolidation phase.
      With a median follow-up duration of 28 months, the 3-year disease-free survival
      rate was 52% (95% confidence interval, 45% to 59%) in the sequential chemotherapy
      arm and 59% (95% confidence interval, 52% to 66%) in the autologous transplant
      arm (P = .46, relative risk = 0.90). The 3-year survival rate did not differ
      between sequential chemotherapy and autotransplantation, at 71% (95% confidence
      interval, 64% to 78%) and 69% (95% confidence interval, 62% to 76%), respectively
      (P = .60, relative risk = 1.11). CONCLUSION: For such a subset of patients,
      consolidation with the CBV regimen followed by autologous bone marrow
      transplantation is not superior to sequential chemotherapy.

PMID- 7527454
TI  - Highly effective induction therapy for stage 4 neuroblastoma in children over 1
      year of age.
AB  - PURPOSE: To test the efficacy of a protocol for poor-risk neuroblastoma that
      builds on the following: (1) our favorable previously reported results with dose
      intensive use of cyclophosphamide; (2) our retrospective analysis of
      neuroblastoma chemotherapy reports, which supported the value of high-dose
      cisplatin and etoposide (VP-16); and (3) the Goldie-Coldman hypothesis that rapid
      cytoreduction plus the use of non-cross-resistant chemotherapy combinations will
      decrease the risk of drug resistance. PATIENTS AND METHODS: The N6 protocol
      included seven courses of high-dose chemotherapy plus surgical resection of bulk
      disease. Courses 1, 2, 4, and 6 consisted of 6-hour intravenous infusions of
      cyclophosphamide 70 mg/kg/d on days 1 and 2 (ie, 140 mg/kg per course), a 72-hour
      intravenous infusion of doxorubicin 75 mg/m2 and vincristine 0.1 mg/kg beginning
      day 1, and vincristine 1.5 mg/m2 intravenous bolus on day 9. Courses 3, 5, and 7
      consisted of 2-hour intravenous infusions of VP-16 200 mg/m2/d on days 1 to 3
      (ie, 600 mg/m2 per course), and 1-hour intravenous infusions of cisplatin 50
      mg/m2/d on days 1 to 4 (ie, 200 mg/m2 per course). Courses were to start after
      neutrophil counts reached 500/microL and platelet counts reached 100,000/microL.
      Response was defined by international criteria. RESULTS: Among 24 consecutive
      previously untreated patients diagnosed with stage 4 neuroblastoma at more than 1
      year of age, 21 patients achieved a complete or very good partial remission; one
      patient had no evidence of disease except by iodine-131-metaiodobenzylguanidine
      (MIBG) scan, which was markedly improved; and one patient had resolution of
      extensive metastatic disease, but still had an incompletely resected primary
      tumor. The sole patient to have a poor response had clinical features at
      diagnosis that are atypical for neuroblastoma, namely, 8 years of age and an
      unknown primary tumor. Severe toxicities included myelosuppression, mucositis,
      and hearing deficits. CONCLUSION: The N6 approach reliably achieves significant
      cytoreduction against stage 4 neuroblastoma. This may eventuate in an improved
      cure rate, since consolidative treatments using myeloablative therapy,
      immunotherapy, or biologic response modifiers such as cis-retinoic acid are most
      likely to be effective against minimal residual disease.

PMID- 7527452
TI  - Induction of tumor necrosis factor alpha gene expression by lipoprotein lipase
      requires protein kinase C activation.
AB  - We have previously found that lipoprotein lipase (LPL) induces tumor necrosis
      factor alpha (TNF alpha) mRNA expression and TNF alpha protein production in the
      ANA-1 macrophage cell line and in resident murine macrophages. The present study
      was designed to elucidate the intracellular signalling pathways involved in the
      LPL-induced TNF alpha gene expression. Treatment of macrophages with two protein
      kinase C (PKC) inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine
      hydrochloride (H7) and calphostin C, suppressed LPL-induced TNF alpha mRNA
      expression and protein production. In contrast, no inhibition of the TNF alpha
      mRNA expression occurred when macrophages were exposed to an inhibitor of
      calmodulin-dependent kinase N-(6-amino-hexyl)-5-chloro-1-naphthalene-sulfonamide
      hydrochloride (W7). Overnight treatment of ANA-1 cells with 100 ng/ml 4 beta
      phorbol 12 beta-myristate 13 alpha-acetate (PMA) caused the suppression of both
      PKC activity and LPL-induced TNF alpha mRNA expression. We have also found that
      LPL treatment increased PKC activity in macrophages and induced a translocation
      of this enzyme from the cytosol to the membrane. Finally, we have demonstrated
      that H7 inhibited the enhancement of nuclear protein binding to the NFkB
      consensus sequence in the promoter of the TNF alpha gene that we observed in LPL
      treated macrophages. Moreover, the treatment of macrophages with H7 abolished the
      stabilization of TNF alpha mRNA in response to LPL. Overall these data
      demonstrate that LPL induces TNF alpha mRNA expression in a PKC-dependent manner
      and that the PKC effect involves transcriptional events as well as
      posttranscriptional modifications.

PMID- 7527455
TI  - Detection of circulating tumor cells in men with localized prostate cancer.
AB  - PURPOSE: Using prostate-specific antigen (PSA) mRNA as a marker for prostatic
      epithelial cells, we have developed a sensitive technique that involves reverse
      transcription and polymerase chain reaction (RT-PCR) to detect circulating tumor
      cells in the peripheral blood of men with prostatic carcinoma (CaP). PATIENTS AND
      METHODS: A sensitive RT-PCR assay was used to evaluate the peripheral blood of
      135 men with a history of CaP. Fourteen men with benign prostate disease, many of
      whom had elevated serum PSA levels, were used as a control group. RESULTS: All
      patients with benign prostate disease had a negative result in the RT-PCR assay.
      Of particular interest was a subgroup of 65 patients with clinically localized
      CaP evaluated before definitive local therapy. Five of these patients had
      detectable PSA mRNA by RT-PCR, suggesting circulating tumor cells. Within this
      group, systemic disease was detected by RT-PCR in some men with PSA levels less
      than 10 ng/mL and clinical stage B disease. Blood from men with hormone
      refractory and progressive CaP demonstrated a higher frequency of PSA mRNA
      detectable by RT-PCR (10 of 20 patients). In contrast, none of seven patients
      with newly diagnosed metastatic prostate cancer and only one of seven patients
      with metastatic, hormone-responsive disease had blood that was positive for PSA
      mRNA by RT-PCR. CONCLUSION: Circulating tumor cells can be detected in the blood
      of a subset of patients with clinically localized CaP and a larger subset of
      patients with progressive metastatic disease.

PMID- 7527457
TI  - The treatment of painful osteoblastic metastases: what can we expect from nuclear
      oncology?

PMID- 7527458
TI  - Strontium-89 for the palliation of bone pain due to metastatic disease.

PMID- 7527459
TI  - Inhibition of Ca2+ entry by Ca2+ overloading of intracellular Ca2+ stores in
      human platelets.
AB  - 1. This study examined the effect of overloading human platelet intracellular
      Ca2+ stores on the rate of agonist-evoked external Ca2+ entry. To overload the
      Ca2+ stores (presumably dense tubules), external Na(+)-dependent Ca2+ efflux via
      Na(+)-Ca2+ exchange was inhibited by pretreating the cells with ouabain or Na(+)
      free medium. Ca2+ regulation was then examined after exposure to thrombin, ADP
      and thapsigargin. Cytosolic free Ca2+ levels were monitored using the fluorescent
      probe fura-2 and external Ca2+ influx was assessed by the rates of extracellular
      Mn2+ or 45Ca2+ uptake. 2. Both ouabain and Na(+)-free pretreatments caused a
      slight increase in the resting cytosolic free Ca2+. 3. In 1 mM Ca(2+)-containing
      medium, Ca(2+)-overloaded platelets showed similar thrombin-evoked cytosolic free
      Ca2+ responses to those of control platelets. However, in Ca(2+)-free medium,
      they showed substantially greater thrombin-evoked cytosolic free Ca2+ responses
      than control platelets. Moreover, increased thrombin-evoked Ca2+ mobilization
      from Ca2+ storage sites was accompanied by a diminished rate of thrombin-evoked
      external Ca2+ entry. 4. Similar reductions in the rate of external Ca2+ entry
      were observed after treatment with ADP and thapsigargin. 5. Protein kinase C
      inhibitors (calphostin C and staurosporine) failed to reverse the effect of
      ouabain pretreatment on thrombin-induced changes in the cytosolic free Ca2+
      response. 6. Inositol 1,4,5-trisphosphate profiles in ouabain-treated and non
      treated platelets were not significantly different. 7. These data indicate that
      increased Ca2+ in the dense tubules is associated with diminished agonist-evoked
      external Ca2+ influx.

PMID- 7527460
TI  - Origin of delayed outward ionic current in charge movement traces from frog
      skeletal muscle.
AB  - 1. Non-linear membrane ionic current was studied in highly stretched cut frog
      twitch fibres in a double Vaseline-gap voltage clamp chamber, with the internal
      solution containing 0.1 mM EGTA and the external solution containing Cl- as the
      major anion. After the Na+ currents was abolished by TTX in the external solution
      and the K+ currents were suppressed by external TEA+ and Rb+ and internal Cs+, a
      delayed outward ionic current with a time course similar to that of the delayed
      rectifier current was observed during depolarization. 2. The delayed outward
      ionic current was resistant to 1 mM 3,4-diaminopyridine (3,4-DAP) in the external
      solution and was unaltered when a fraction of the internal Cs+ was replaced by K+
      or Na+, suggesting that the current was not carried by cations flowing through
      the delayed rectifiers. 3. The delayed outward ionic current was greatly reduced
      by replacing the external Cl- with CH3SO3-,SO4(2-), glutamate or gluconate,
      indicating strongly that the current was carried by Cl- flowing through anion
      channels. The current was also suppressed by 1 mM external 9-anthracenecarboxylic
      acid (9-ACA). 4. The delayed outward ionic current was reduced by blockers of
      calcium-dependent Cl- channels, such as SITS and frusemide (furosemide), in a
      dose- and voltage-dependent manner and by increasing intracellular [EGTA] to 20
      mM, suggesting that part of the Cl- current in the muscle fibres could be calcium
      dependent. 5. The total Cl- current could be dissected into calcium-dependent and
      calcium-independent components. Each component accounted for roughly half of the
      total Cl- current. The maximum slope conductance of the calcium-dependent Cl-
      channels was 60.9 +/- 6.0 microS microF-1 (mean +/- S.E.M., n = 4).

PMID- 7527456
TI  - Phase I study of topotecan and cisplatin in patients with advanced solid tumors:
      a cancer and leukemia group B study.
AB  - PURPOSE: The objectives of this phase I trial were to determine the dose-limiting
      toxicities (DLTs) of the novel topoisomerase I inhibitor topotecan combined with
      cisplatin, to define the maximum-tolerated doses (MTDs) of the combination
      without and with the use of filgrastim, and to define recommended doses for phase
      II trials. PATIENTS AND METHODS: Patients with advanced solid tumors were
      eligible if they had normal bone marrow, renal, and hepatic function and had not
      previously been treated with platinum compounds. Topotecan was administered
      intravenously on days 1 through 5 and cisplatin was administered intravenously on
      day 1 of a 21-day cycle. The topotecan dose was fixed at 1.0 mg/m2/d on the first
      four dose levels, and cisplatin was escalated in 25-mg/m2 increments from 25 to
      100 mg/m2 without filgrastim. After encountering DLT, the dose of cisplatin was
      decreased by one level and topotecan dose escalation was attempted. After
      defining the MTD without growth factor, the study proceeded with escalating
      cisplatin doses to define the MTD with filgrastim 5 micrograms/kg subcutaneously
      (SC) daily starting on day 6 of treatment. Priming with filgrastim 5
      micrograms/kg SC on days -6 to -2 before the first course was explored last.
      RESULTS: Of 38 patients entered, 37 were eligible, 35 assessable for toxicity in
      the first course, and 28 assessable for response. The principal toxicity was
      grade 4 neutropenia, which had to last more than 7 days to be considered dose
      limiting. No DLT was observed at the starting cisplatin dose of 25 mg/m2 (dose
      level 1). On level 2 (cisplatin 50 mg/m2, one patient had dose-limiting
      neutropenia and one patient had grade 3 renal toxicity. On level 3 (cisplatin 75
      mg/m2), two patients had dose-limiting neutropenia. Therefore, cisplatin dose
      escalation was stopped. On dose level 5 (cisplatin 50 mg/m2 and topotecan 1.25
      mg/m2/d), one patient had grade 4 neutropenia that lasted more than 7 days and
      one patient died of neutropenic sepsis. The remaining dose levels used topotecan
      1.0 mg/m2/d plus cisplatin 75 mg/m2 (level 6) and 100 mg/m2 (levels 7 and 8) with
      filgrastim. No DLT was observed on level 6. On level 7, two patients had dose
      limiting neutropenia and one patient had grade 3 hyperbilirubinemia. Priming with
      filgrastim on level 8 demonstrated no obvious advantage over level 7, and one
      patient had grade 4 thrombocytopenia that lasted more than 7 days. Three patients
      with non-small-cell lung cancer achieved a partial response and one patient with
      breast cancer had a complete response. CONCLUSION: Topotecan and cisplatin in
      combination cause more neutropenia than expected from either drug given alone at
      the same dosage. The recommended phase II doses are topotecan 1.0 mg/m2/d for 5
      days in combination with cisplatin 50 mg/m2 on day 1 without filgrastim or
      cisplatin 75 mg/m2 on day 1 with filgrastim support.

PMID- 7527462
TI  - Marginal seal of new-generation dental bonding agents.
AB  - This in vitro study evaluated microleakage of three new adhesive systems--All
      Bond 2, Gluma 2000, and Scotchbond Multi-Purpose. Enamel was removed from the
      buccal surfaces of 40 extracted molars, and cavity preparations were made on both
      the buccal and lingual surfaces of each tooth. Buccal cavities were entirely in
      dentin, and the lingual cavities had enamel margins. Specimens were randomly
      assigned to three groups for treatment with All-Bond 2, Gluma 2000, or Scotchbond
      Multi-Purpose adhesive systems. A fourth group of specimens was untreated to
      serve as the control. All cavity preparations were restored with a visible light
      cured microfilled composite resin. Specimens were thermocycled and subjected to a
      crystal violet staining technique to detect marginal microleakage. Microleakage
      was recorded as ordinal data and analyzed with nonparametric statistical tests.
      Each of the adhesives tested significantly reduced microleakage at the enamel and
      dentin margins. The extent of leakage at dentin margins was only slightly greater
      than at enamel margins in each treatment group.

PMID- 7527463
TI  - 1,2,3-Triazole-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D- ribofuranosyl]-3'
      spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO) analogues: synthesis and
      anti-HIV-1 activity.
AB  - Several 4- or 5-monosubsituted and 4,5-disubstituted 1,2,3-triazole analogues of
      the anti-HIV-1 lead compound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-
      ribofuranosyl]thymine]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO
      T) have been prepared and evaluated as inhibitors of HIV-1-induced cytopathicity.
      These analogues have been prepared by 1,3-diplar cycloaddition of [2,5-bis-O
      (tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3-spiro-5'-(4'-amino- and 4'-(N
      acetylamino)-1',2'-oxathiole 2',2'-dioxide) (TSAO) azides to various substituted
      acetylenes. Several 4- and 5-substituted 1,2,3-triazole-TSAO analogues proved
      superior to the unsubstituted derivative by 1-2 orders of magnitude. In
      particular the 5-substituted amido-, (methylamido)-, and (dimethylamido)-1,2,3
      triazole derivatives of TSAO were endowed with potent anti-HIV-1 activity (50%
      effective concentration: 0.056-0.52 microM). They show a similar resistance
      spectrum as previously noted for TSAO-T and related derivatives.

PMID- 7527461
TI  - A unique amino acid of the Drosophila GABA receptor with influence on drug
      sensitivity by two mechanisms.
AB  - 1. The Drosophila gene Rdl (resistance to dieldrin) encodes a GABA receptor. An
      alanine-to-serine mutation in this gene at residue 302 confers resistance to
      cyclodiene insecticides and picrotoxin. Patch clamp analysis of GABA receptors in
      cultured neurons from wild type and mutant Drosophila was undertaken to
      investigate the biophysical basis of resistance. 2. In cultured neurons from both
      wild type and mutant strains, GABA activated a channel that reversed near 0 mV in
      symmetrical chloride. GABA dose-response characteristics of wild type and mutant
      receptors were very similar. 3. GABA responses in neurons from the mutant strains
      showed reduced sensitivity to the GABA antagonists picrotoxin, lindane and t
      butyl-bicyclophosphorothionate. Resistance ratios were 116, 970 and 9 for the
      three blockers, respectively. Inhibition increased with blocker concentration in
      a manner consistent with saturation of a single binding site. 4. The mutation
      reduced the single channel conductance by 5% for inward current and 17% for
      outward current. The single channel current was approximately 60% lower for
      outward current than for inward current in both wild type and mutant. 5. Open and
      closed times were both well fitted by the sum of two exponentials. Resistance was
      associated with longer open times and shorter closed times, reflecting a net
      stabilization of the channel open state by a factor of approximately five. 6. The
      mutation was associated with a marked reduction in the rate of GABA-induced
      desensitization, and a net destabilization of the desensitized conformation by a
      factor of 29. 7. The Rdl mutation manifests resistance through two different
      mechanisms. (a) The mutation weakens drug binding to the antagonist-favoured
      (desensitized) conformation by a structural change at the drug binding site. (b)
      The mutation destabilizes the antagonist-favoured conformation in an allosteric
      sense. The global association of a single amino acid replacement with cyclodiene
      resistance suggests that the resistance phenotype depends on changes in both of
      these properties, and that insecticides have selected residue 302 of Rdl for
      replacement because of its unique ability to influence both of these functions.
      8. The location of alanine 302 in the sequence of the Rdl gene product supports a
      mechanism of action in which convulsants such as picrotoxin bind within the
      channel lumen, where they induce a rapid conformational change to the
      desensitized state.

PMID- 7527464
TI  - Selection of phage-displayed antibodies specific for a cytoskeletal antigen by
      competitive elution with a monoclonal antibody.
AB  - A phage-display combinatorial library of VL and VH sequences of mouse antibodies
      was constructed, which contained 4.5 x 10(7) independent clones. From this
      library pools of phage were selected by up to four biopanning rounds on
      cytoskeletal preparations of ovarian carcinoma cells (OVCAR-3). Phage of these
      pools were then allowed to bind to a cytoskeleton preparation of bladder
      carcinoma cells (T24). The binding phage were challenged by a monoclonal antibody
      (mAb) directed against an epitope on cytokeratin 8. Displaced phage were rescued
      and screened for anti-cytokeratin immunoreactivity by ELISA, indirect
      immunofluorescence and Western blotting. About 50% of the phage selected by
      competition with the cytokeratin mAb reacted with the cytoskeletal preparations
      of T24 cells in ELISA. In contrast, in non-cytokeratin-containing cells, no
      reaction was observed. Immunofluorescence and Western blotting studies with a
      number of these clones showed reactivity against cytokeratin. We conclude that
      the phage-display competitive elution method can be used as a rapid technique to
      obtain immunoreactive phages, and eventually single-chain Fv (scFv) antibodies
      directed against defined epitopes, which were formerly characterized and
      validated by mAbs.

PMID- 7527465
TI  - Crystallization and preliminary X-ray diffraction characterisation of both a
      native and selenomethionyl VLA-4 binding fragment of VCAM-1.
AB  - Soluble fragments of the extracellular region of vascular cell adhesion molecule
      1 (VCAM-1) expressed in Escherichia coli retain functional adhesive activity. An
      integrin (VLA-4) binding fragment consisting of the N-terminal two immunoglobulin
      like domains (VCAM-d1,2) has been crystallized. The crystals belong to space
      group P2(1)2(1)2(1) with cell dimensions of a = 52.7 A, b = 66.5 A, c = 113.2 A
      and contain two molecules in the crystallographic asymmetric unit. A batch of
      protein produced in the standard E. coli strain (HW1110), but grown in the
      presence of selenomethionine enriched media, showed 85% incorporation of selenium
      in place of sulphur at methionine residues. The selenomethionyl VCAM-d1,2 was
      crystallized by microseeding techniques initially using the native crystals for
      nucleation. Both native and selenomethionyl crystals diffract X-rays to a minimum
      Bragg spacing of 1.8 A.

PMID- 7527466
TI  - Cleavage site selection by M1 RNA the catalytic subunit of Escherichia coli RNase
      P, is influenced by pH.
AB  - We have studied cleavage site selection by M1 RNA, the catalytic subunit of
      Escherichia coli RNase P, under various reaction conditions using tRNA precursors
      which are cleaved at two positions. Our results showed that the preference of
      cleavage site changed with variations in pH or Mg2+ concentration. By contrast,
      no difference in cleavage site selection was observed with increasing pH in the
      presence of Ca2+ as the only divalent metal ion. Depending on the identity of the
      nucleotide at position "+ 72", replacement of Mg2+ with Ca2+ resulted in a change
      of the main cleavage site irrespective of pH. We conclude that cleavage in the
      presence of Ca2+ compared to cleavage in the presence of Mg2+ has different
      structural requirements at and near the cleavage site. UV cross-linking revealed
      that close points between M1 RNA and its substrate were the same irrespective of
      pH or the identity of the divalent cation. Our results also showed that the
      observed pH effects are due to changes in the catalytic cleavage rates rather
      than to global, structural rearrangements. These data are discussed in terms of
      metal ion binding near the cleavage sites in the enzyme-substrate complex.

PMID- 7527467
TI  - Bases defining an ammonium and magnesium ion-dependent tertiary structure within
      the large subunit ribosomal RNA.
AB  - A 58 nucleotide RNA derived from a highly conserved domain of the large subunit
      ribosomal RNA (Escherichia coli 1051 to 1108) has a set of tertiary interactions
      that is stabilized by NH4+ and Mg2+ in preference to other ions. We have mapped
      the nucleotides contributing to this structure by examining the thermal
      denaturation of 25 sequence variants. Where necessary compensatory mutations were
      made to preserve the phylogenetically conserved secondary structure.
      Substitutions of bases or base-pairs at eight positions specifically eliminate
      the ion-dependent tertiary structure without affecting the secondary structure
      stability; most of these positions are conserved among all large subunit RNA
      sequences. At two positions, substitutions of bases found in other organisms
      stabilize the E. coli tertiary structure by substantial amounts (delta G 37
      degrees becomes more favorable by -1.8 to -4.5 kcal/mol). One of these variants
      disrupts a potential A.U base-pair within a helix, suggesting that the tertiary
      structure competes with alternative structures. The results show that this rRNA
      domain contains an extensive, highly conserved, and very stable set of tertiary
      interactions. The sequence in E. coli, and probably most other organisms, has not
      evolved to maximum stability. It is possible that natural selection has "tuned"
      the tertiary structure to an optimum stability, perhaps because the structure
      must open and close during the ribosome cycle.

PMID- 7527468
TI  - Cutting edge meets clinic in treatment research.

PMID- 7527470
TI  - [Prostate specific antigen in patients with prostatic cancer--clinical usefulness
      of its measurement with sensitive enzyme immunoassay, TOSOH II PA assay].
AB  - The TOSOH II PA (AIA-PACK PA in the U.S.A.) monoclonal immunoenzyme assay was
      used and the clinical usefulness of prostate specific antigen (PSA) was evaluated
      in 39 men with prostatic cancer and 32 men with benign prostatic hyperplasia
      (BPH) confirmed pathologically. We evaluated the lower limit of detection in this
      assay by the mean PSA level plue 3 standard deviations in 5 separate experiments
      with a zero control sera as well as the mean PSA level minus 3 standard
      deviations in 5 separate experiments with serial dilutions of a known
      concentration of PSA. PSA concentrations of 0 to 0.25 ng/ml could not be
      distinguished from the zero control. Therefore, we set the lower limit of
      detection for the assay as 0.25 ng/ml. At our laboratory, the normal standard
      value was determined by the mean PSA level plus 3 standard deviations in 79
      healthy men as 2.3 ng/ml. Of patients that underwent radical cystoprostatectomy
      for bladder cancer, all had PSA levels less than 0.25 ng/ml, while only 6% had
      PAP levels less than 0.11 ng/ml, the lower limit of detection in the TOSOH II PAP
      assay. We compared TOSOH II PA with Markit PA, a commonly used assay in Japan.
      Although there was a close linear correlation (r = 0.90) between the TOSOH II PA
      and Markit PA, the difference of slope in the linear regression lines was great,
      it was thought due to anti-PSA antibodies in each assay recognizing different
      epitopes of PSA in the blood.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527471
TI  - [Experimental studies on the role of lactic acid in pathogenesis of
      neovascularization].
AB  - In order to elucidate the controversies whether lactic acid could be the factor
      responsible for the initiation of neovascularization, the author examined
      neovascular response of the vessels of the chicken chorioallantoic membrane after
      implantation of filter discs soaked with different concentrations of this
      substance. No neovascularization of the vessels of the membrane was seen after
      implantation of the discs. The results of the study suggest that lactic acid is
      not the factor which can stimulate neovascularization.

PMID- 7527472
TI  - Hay fever: pharmacotherapy or immunotherapy?
AB  - The total management of the patient with hay fever involves a multifaceted
      approach including environmental control, pharmacotherapy, and immunotherapy.
      Pharmacotherapy and immunotherapy are complementary methods which the allergist
      may utilize as appropriate to each individual patient's needs.

PMID- 7527469
TI  - Histological and functional studies on the nitroxidergic nerve innervating monkey
      cerebral, mesenteric and temporal arteries.
AB  - Nitroxidergic nerves and their functional role were determined in a variety of
      monkey arteries. Nitric oxide synthase-immunoreactive nerve fibers innervating
      the monkey arterial wall were histochemically determined by the use of nitric
      oxide synthase antiserum. Thin nitric oxide synthase-immunoreactive fibers were
      consistently found in the outer media of monkey cerebral, mesenteric and temporal
      arteries, in addition to many thicker fibers and nerve bundles in the adventitia.
      In the monkey pterygopalatine ganglion, the immunoreactivity was clearly seen in
      nerve cells, bundles and fibers. Helical strips of monkey arteries were exposed
      to the bathing media for tension recordings and were stimulated by electrical
      square pulses. In helical strips of the cerebral artery denuded of the
      endothelium, transmural electrical stimulation produced relaxations that were
      abolished by tetrodotoxin or NG-nitro-L-arginine, a nitric oxide synthase
      inhibitor. In the monkey mesenteric and temporal arterial strips treated with
      alpha-adrenoceptor antagonists, the relaxation caused by electrical stimulation
      was also abolished by the nitric oxide synthase inhibitor, and it was restored by
      L-arginine. Nitroxidergic perivascular nerves, histologically demonstrated,
      appear to play an important role in dilating the monkey cerebral artery and in
      counteracting a vasoconstriction associated with noradrenergic nerve activation
      in the mesenteric and temporal arteries.

PMID- 7527473
TI  - If surgery is the last option for sinusitis, what is the first?
AB  - While sinusitis effects a great many patients, the vast majority of can be
      controlled with medical therapy. Understanding the physiology and aggressively
      treating infection will prevent many chronic problems from developing.

PMID- 7527474
TI  - Whipple's disease presenting with near fatal gastrointestinal bleeding.

PMID- 7527475
TI  - Connectivity of neurons in identified auditory circuits studied with transport of
      dextran and microspheres plus intracellular injection of lucifer yellow.
AB  - The components of a neural circuit are usually distinguished in separate
      experiments to identify long connections, presynaptic, and postsynaptic
      components. We describe a procedure to visualize these components in the same
      experiment. Neurons in the inferior colliculus the axons of which project to the
      medial geniculate body were identified by retrograde transport of latex
      microspheres, while their innervation from the cochlear nucleus was
      simultaneously visualized by anterograde transport of dextrans. In aldehyde-fixed
      slices, the microsphere-labeled neurons near dextran-labeled axons were injected
      with biotinylated Lucifer Yellow. Subsequent avidin-biotin histochemistry allowed
      permanent visualization. The specific neurons involved in this circuit and the
      axonal contacts they received were easily visualized with the light microscope.
      This method allows the study of complex innervation patterns in the mammalian
      central nervous system.

PMID- 7527477
TI  - Physiological concentrations of melatonin inhibit nitric oxide synthase in rat
      cerebellum.
AB  - In the present paper we show the inhibitory effect of melatonin on rat cerebellar
      nitric oxide synthase (NOS) activity. NO production was monitored by the
      stoichiometric conversion of L-arginine to L-citrulline. The inhibitory effect of
      melatonin was dose-dependent, with an IC50 value of about 0.1 mM. However, a
      significant inhibition of enzyme activity (> 22%) was observed at 1 nM melatonin
      which is in the range of the physiological serum concentration of the hormone at
      night. The inhibitory effect of melatonin was observed exclusively in the
      presence of Ca++. Results suggest a new and important role of the pineal hormone
      melatonin on central nervous system processes, i.e., by modulating NO production.

PMID- 7527476
TI  - Efficacy of seven retrograde tracers, compared in multiple-labelling studies of
      feline motoneurones.
AB  - The labelling efficacies of 7 retrograde tracers were evaluated following cut
      nerve exposure or intramuscular injection into the serially compartmentalized
      neck muscle, biventer cervicis. Tested tracers included Fast Blue (FB),
      Fluorogold (FG), dextran conjugated to fluorescein (FD), dextran conjugated to
      rhodamine (Fluororuby (FR), 3000 and 10,000 MW), fluorescent latex microspheres,
      horseradish peroxidase coupled to colloidal gold, and 1,1'-dioctadecyl-3,3,3',3'
      tetramethyl indocarbocyanine perchlorate (DiI). In 2 animals, horseradish
      peroxidase was also employed and spinal cords were processed for peroxidase
      activity to evaluate its effect on the appearance of cells labelled with
      fluorescent tracers. Four tracers, FB, FG, FD and FR, could be observed in
      motoneurones under the conditions of our study. FB and FG labelled comparable
      numbers of motoneurones following cut nerve exposure, but dissimilar numbers
      following intramuscular injection. FG diffused extensively following injection
      and was found in motoneurones not only in the appropriate ipsilateral segment but
      also adjacent ipsilateral and contralateral segments. Intramuscular injections of
      FB usually labelled fewer cells than cut nerve exposure, but evidence for
      spurious labelling following intramuscular injection could also be found. FD or
      FR labelled motoneurones following cut nerve exposure but not following
      intramuscular injection. The conjugated dextrans labelled more variable numbers
      of cells than FB or FG, but the labelled cells had similar patterns of
      distribution. The remaining tracers were ineffective as retrograde markers in our
      study, and the possible reasons for these failures are discussed.

PMID- 7527478
TI  - Basic fibroblast growth factor and de novo mammalian angiogenesis.
AB  - Using the rat mesenteric-window assay, the de novo angiogenic effect of basic
      fibroblast growth factor (bFGF) in the intact, adult, normally vascularized test
      tissue was analyzed using quantitative microscopy including image analysis. Basic
      FGF was injected ip at doses of 10, 100, and 1000 ng twice daily for 4.5 days and
      the animals, which were not subjected to surgery, were sacrificed in groups every
      week for 6 consecutive weeks. The scale and dynamics of the angiogenic response
      were measured in terms of variables related to microvascular spatial expansion
      and density. The growth factor-induced angiogenesis in a dose-dependent,
      nonlinear manner and the angiogenesis displayed distinctly dose-dependent
      kinetics. The middle dose thus caused angiogenesis that peaked already at Day 7,
      thereby suggesting a direct effect. The high dose caused angiogenesis that peaked
      at Day 14, which also appears to be compatible with a direct effect. The low dose
      caused a more prolonged angiogenic response which did not peak until Day 21 or
      28, depending on which variable was measured, which is indicative of an indirect
      effect. Clearly, the findings suggest that the molecular and cellular mechanisms
      of bFGF-mediated angiogenesis are dose-dependent.

PMID- 7527479
TI  - [Identification of the bacterium Pseudomonas mallei using Pseudomonas
      pseudomallei bacteriophages].
AB  - Phage production by Pseudomonas pseudomallei and Pseudomonas mallei strains has
      been studied. 32 P. pseudomallei bacteriophages have been isolated. Their
      spectrum of lytic action against P. pseudomallei, P. mallei and other Pseudomonas
      sp. has been defined. It has been shown that P. pseudomallei bacteriophages PP19,
      PP23, PP33 may be used for identification P. mallei among related Pseudomonas.

PMID- 7527482
TI  - [Analysis of effectiveness of cDNA synthesis, induced using complementary primers
      and primers containing a noncomplementary base matrix].
AB  - We have studied the efficiency of DNA synthesis catalyzed by M-MLV reverse
      transcriptase or Thermus aquaticus DNA polymerase for primers (4-17 nucleotides
      long) either completely matched or possessing a single mismatched base pair at
      all possible positions in the primer. It has been shown that DNA synthesis
      efficiency depends not only on the position of mismatched base pair but on the
      length and primary structure of the primer. The enzyme, template, and primer
      concentrations determine the relative level of mismatched DNA synthesis.

PMID- 7527481
TI  - [Samples of the protein family for comparing amino acid sequences].
AB  - A method to develop images of protein families for fast comparison with any amino
      acid sequences is proposed. The method is based on physico-chemical properties of
      amino acids and on the choice of fragments of amino acid sequences of protein
      families that maximally distinguish the sequences from members of other families
      or random sequences. The efficiency of the method is demonstrated on comparison
      of images developed for protein families of alpha-interferons, alpha-hemoglobins,
      long neurotoxins, and DNA polymerases with the SWISS-PROT data bank.

PMID- 7527480
TI  - On the oncodevelopmental role of human imprinted genes.
AB  - Genome imprinting has an essential role in normal embryonal mammalian
      development. Starting early in differentiation, the transcripts of certain human
      genes, e.g. the paternally-H19 and the maternally-imprinted IGF2, are expressed
      in specific tissues and organs during fetal life. In several malignant disorders,
      imprinted genes are, again, unfolded. Characteristically, expression follows the
      same tissue presentation as during embryogenesis. Clinical paternal disomies,
      i.e. trophoblastic diseases, and their maternal counterpart, i.e. ovarian
      teratomas, are associated with apparent relaxation of imprinting once they turn
      malignant. Paediatric neoplasms, like Wilm's tumor (WT) and rhabdomyosarcoma,
      often express IGF2 and H19. Recently, we have found H19 expression in invasive
      urothelial cancer. Evidently, imprinted genes display an oncodevelopmental mode
      of expression, very much like the classical oncofetal proteins AFP and CEA. Based
      on available data, including tumor preferential paternal allele retention and
      chromosome 11 short arm physical linkage with oncogenes like H-ras, we
      hypothesize that imprinted genes not only accompany cancer but may play a
      causative role as well.

PMID- 7527483
TI  - Early onset Parkinson's disease: are juvenile- and young-onset different?
AB  - It is controversial if early onset Parkinson's disease (EOPD) (onset at < 41
      years of age) is Parkinson's disease (PD) occurring at a younger age or a
      different disease. This controversy is due to some clinical and pathological
      differences between EOPD and PD. Within EOPD, there appear to be two groups
      namely: young onset Parkinson's disease (YOPD), with onset between 21 and 40
      years, and juvenile parkinsonism (JP), with onset at < 20 years. The two major
      clinical differences between these groups are a higher familial occurrence of PD
      and dystonia in JP. In this study, we determine if the two groups have the
      classical features of PD, namely rest tremors, rigidity, bradykinesia, and
      postural instability, and have a meaningful response to levodopa. Furthermore, we
      compare their other clinical features, autonomic and cognitive functions, and
      levels of CSF monoamine metabolites to determine differences between these
      groups. We observe that all YOPD (100%) and JP (85%) patients had rest tremors.
      Most of these patients also had a meaningful response to levodopa (YOPD: 72%; JP:
      100%). The prevalence of family history of PD was similar, whereas dystonia was
      more frequent in JP (43%) compared to YOPD (9%). Autonomic symptoms were twice as
      common in JP (42%) compared to YOPD (17%). However, bedside autonomic functions
      were abnormal in similar proportions and, like in PD, suggest involvement of
      parasympathetic nervous system. Cognitive dysfunction does occur but with no
      difference in severity between the two groups. The difference in number of
      patients between YOPD and JP groups makes statistical comparison of the
      occurrence of clinical features like dystonia and autonomic dysfunction
      difficult.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527484
TI  - A re-evaluation of the cytogenetic effects of styrene.
AB  - Results from new chromosome studies in laboratory animals, comparative
      investigations of styrene metabolism and pharmacokinetics in humans and animals,
      and several recent cytogenetic surveys of styrene-exposed workers have
      necessitated a comprehensive re-evaluation of the chromosome-damaging effects of
      this chemical. Both styrene and its genotoxic metabolite, styrene oxide, can
      induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in vitro,
      but the chromosome-damaging ability of styrene is only manifested if test
      conditions favour its metabolic activation over inactivation. There is no
      convincing evidence of styrene clastogenicity in experimental animals. Styrene
      oxide is clastogenic only at lethal concentrations via i.p. injection in Chinese
      hamsters (but not via inhalation) or after oral treatment of mice, a route
      considered inappropriate for investigating the chromosome-damaging potential of
      inhaled styrene in man. Styrene and styrene oxide can induce SCE in animals at
      very high concentrations. Eighteen of 52 cytogenetic studies (CA, micronuclei,
      SCE) on peripheral blood lymphocytes of styrene workers have reported increases
      in chromosome damage. The positive findings are not compatible with the
      conclusion that styrene is responsible for the cytogenetic effects for the
      following reasons. (a) The positive or negative outcome of the various
      investigations bears no relationship to the degree of exposure of the workers.
      (b) There is no convincing evidence of a positive dose response relationship. (c)
      The relative induction of CA and SCE in worker studies are the opposite of
      observations of styrene effects in cultured lymphocytes and in laboratory
      animals. (d) The reports of chromosome-type exchanges in some studies of styrene
      workers is inconsistent with observations of styrene clastogenicity in cultured
      lymphocytes. (e) Reports of SCE induction in workers exposed to low
      concentrations of styrene are not compatible with results of animal inhalation
      studies, particularly in view of the differences in styrene metabolism and
      pharmacokinetics between humans and rodents. The increases in cytogenetic effects
      reported in some studies on styrene workers are probably attributable to the
      presence of other chromosome-damaging agents in the workplace and/or to
      inadequate investigations.

PMID- 7527485
TI  - DNA damage and mutagenesis induced by nitrogen mustards.
AB  - The nitrogen mustards are bifunctional alkylating agents which, although used
      extensively in cancer chemotherapy, are themselves highly carcinogenic. All
      nitrogen mustards induce monofunctional guanine-N7 adducts, as well as
      interstrand N7-N7 crosslinks involving the two guanines in GNC.GNC (5'-->3'/5'-
      >3') sequences. In addition, the aromatic mustards melphalan and chlorambucil
      also induce substantial alkylation at adenine N3, while cyclophosphamide forms
      phosphotriesters with relatively high frequency. Nitrogen mustards are genotoxic
      in virtually every assay, and produce a wide array of mutations, including base
      substitutions at both G.C and A.T base pairs, intragenic as well as multilocus
      deletions, and chromosomal rearrangements. Mutational spectra generated by these
      agents in various model systems vary widely, and no single lesion has been
      implicated as being primarily responsible for mustard-induced mutagenesis. On the
      contrary, adducts of both adenine and guanine, and monofunctional as well as
      bifunctional adducts, appear to be involved. Further, it is still not known which
      types of mutation are responsible for mustard-induced cancers, since no genes
      have yet been identified which are consistently altered in these malignancies.

PMID- 7527486
TI  - Nucleoside and nucleobase analog mutagens.
AB  - Compounds with structures close to those of normal nucleosides or nucleobases may
      be incorporated into cells and then become constituents of their DNA.
      Proliferation of such cells could yield mutants. In this article, the current
      status of studies on such nucleoside and nucleobase analogs is described. Base
      mispairing mechanisms for these analogs are discussed in light of recent
      biochemical and biophysical findings.

PMID- 7527487
TI  - Chlorophyll and chlorophyllin as modifiers of genotoxic effects.
AB  - Reports on an inverse relationship between the consumption of fresh vegetables
      and human gastrointestinal cancer have been followed by screening for the
      protective activity of a large number of plant extracts, including leafy
      vegetables. Chlorophyll is ubiquitous in all green plant parts. Chlorophyllins
      are derivatives of chlorophyll in which the central magnesium atom is replaced by
      other metals, such as cobalt, copper or iron. An attempt has been made in this
      article to review the relative efficacy of chlorophyll and chlorophyllin in
      modifying the genotoxic effects of various known toxicants.

PMID- 7527488
TI  - Sister chromatid exchange frequency is elevated and cell proliferation is delayed
      in bone marrow cells of starved and marginally malnourished rats.
AB  - The frequency of sister chromatid exchanges (SCE) and the cell proliferation
      kinetic were analyzed in bone marrow (BM) cells of Wistar rats subjected to
      starvation and marginal malnutrition (MN) after 24h of 5-bromodeoxyuridine (BdUr)
      implantation. SCE were analyzed in a minimum of 18 consecutive second division
      metaphases and for cell proliferation, 100 consecutive metaphases were analyzed
      and classified into the first, second and third or subsequent replication cycles.
      Rats subjected to starvation and MN exhibited significantly higher mean SCE per
      lymphocyte in bone marrow than the well nourished rats. Further, they also showed
      a longer proliferation kinetic in BM cells. These observations indicate that
      starvation and MN per se resulted in greater SCE and prolongation of the cell
      cycle in experimental animals. On rehabilitation, the cells with high SCE
      frequency and prolonged cell cycle in both starved and MN rats were comparable to
      control groups.

PMID- 7527489
TI  - The performance of short-term tests in identifying potential germ cell mutagens:
      a qualitative and quantitative analysis.
AB  - A retrospective analysis was undertaken to assess the performance of selected
      short-term tests in the discrimination of mammalian germ cell mutagens and
      nonmutagens using data derived from the U.S. Environmental Protection
      Agency/International Agency for Research on Cancer Genetic Activity Profile
      (EPA/IARC GAP) and EPA GENE-TOX databases. The short-term tests selected were
      gene mutation in Salmonella (S. typhimurium), cultured mammalian cell gene
      mutation and chromosomal aberrations, and mammalian bone marrow cytogenetics
      (micronucleus and chromosomal aberrations). These are the first level tests used
      in the EPA mutagenicity testing guidelines. The results of this analysis showed
      good sensitivity of short-term in vitro tests for mammalian cell gene mutation
      (96%) or chromosomal aberrations (92%) in identifying germ cell mutagens, while
      the sensitivity of tests for gene mutation in S. typhimurium was lower (79%).
      Bone marrow micronucleus or chromosomal aberration assays in vivo each displayed
      a sensitivity of 96%. Thus, both the in vitro and in vivo tests may be used
      effectively to screen chemicals for potential germ cell mutagenicity. In
      contrast, the in vitro tests mentioned above performed poorly in discriminating
      putative germ cell nonmutagens, giving results for specificity at or below what
      is expected due to chance alone (50-11%). The bone marrow assays were more
      efficient in this regard, the micronucleus test yielding a specificity of 63% and
      the chromosomal aberrations assay 64%. The mouse bone marrow micronucleus test
      also performed well on a quantitative basis, responding at or below the lowest
      effective doses tested in the mouse dominant lethal assay. Regression analysis of
      the mean lowest effective doses of chemicals evaluated in vivo showed
      approximately 1:1 linear correlations for mouse germ cell assays (heritable
      translocation vs dominant lethal or specific locus tests) as well as for mouse
      bone marrow assays (micronucleus vs chromosomal aberration). The results suggest
      the value of the bone marrow micronucleus test as an assay for potential germ
      cell mutagenicity and the dominant lethal test as a relatively inexpensive choice
      for confirmation of germ cell damage. The sensitivity of the in vitro assays
      investigated and the discriminatory capability of the in vivo bone marrow assay
      affirmed the utility of these tests within the framework of the EPA mutagenicity
      testing guidelines.

PMID- 7527490
TI  - Induction of DNA strand breaks by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)
      furanone and humic substances in relation to glutathione and calcium status in
      human white blood cells.
AB  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) induced DNA strand
      breakage (measured by fluorometric analysis of DNA unwinding) in human white
      blood cells at sub-cytotoxic doses (1.0-1000 microM; 60 min exposure). Although a
      dose-dependent decrease in glutathione levels was observed with MX, this is not
      necessarily the causative factor in the observed DNA damage, since no strand
      breakage was seen on depletion of cellular glutathione to 23% of control by
      diethylmaleate. In addition, the strand scission does not appear to be mediated
      by elevation of intracellular calcium as no MX-induced release of calcium stores
      was observed. Strand breakage may, however, be Ca(2+)-dependent as evidenced by
      inhibition following deprivation of Ca2+ by Quin-2. Chlorinated fulvic acids (> 3
      micrograms/ml) also depleted glutathione and induced strand breaks at sub
      cytotoxic doses (up to 300 micrograms/ml) on prolonged exposure (60 min). The
      unchlorinated material was, however, equally able to cause DNA strand breakage
      (without glutathione depletion). MX appears, therefore, to be only one of a
      number of components of chlorinated humic substances able to induce DNA strand
      breakage.

PMID- 7527491
TI  - Induction of chromosome loss in yeast by combined treatment with neurotoxic
      hexacarbons and monoketones.
AB  - The neurotoxic hexacarbon compounds n-hexane, 2-hexanone and 2,5-hexanedione were
      tested in combination with acetone and methyl ethyl ketone for the potential to
      induce chromosome loss in strain D61.M of Saccharomyces cerevisiae. n-Hexane and
      2-hexanone, alone or in combination, induced only marginally positive chromosome
      loss, whereas the metabolite and presumed proximal genetically active agent 2,5
      hexanedione was strongly positive when tested alone and in combination. These
      observations are discussed in relation to the reported potentiation of the
      neurotoxic effects of these hexacarbons when exposure results from combinations
      with other solvents, e.g., acetone and methyl ethyl ketone. Treatments that
      result in neurotoxicity in experimental animals and humans and those that result
      in chromosome loss in a yeast genetic test system may be correlated by their
      activity on a common intracellular target.

PMID- 7527492
TI  - Genotoxicity assessment of aromatic amines and amides in genetically engineered
      V79 cells.
AB  - A genetically engineered V79 cell line expressing rat CYP1A2 and another cell
      line expressing rat CYP1A2 as well as endogenous acetyltransferase activity, as
      well as CYP-deficient parental V79 cell lines, were used to assess the
      genotoxicity of the aromatic amines and amides 2-aminoanthracene, 2
      aminofluorene, 2-acetylaminofluorene, 4-acetylaminofluorene and 2-amino-3
      methylimidazo[4,5-f]quinoline, with chromosomal aberrations and sister chromatid
      exchanges as the end-points. None of the test compounds showed a clear effect on
      the frequency of chromosomal aberrations in any cell line used. Sister chromatid
      exchanges, however, were induced by 2-aminoanthracene, 2-aminofluorene and 2
      acetylaminofluorene in the CYP1A2-proficient cells, but not in the CYP1A2
      deficient cells. The presence of acetyltransferase activity enhanced the effect
      of 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene. 4
      Acetylaminofluorene and 2-amino-3-methylimidazo[4,5-f]quinoline did not induce
      sister chromatid exchanges in the investigated cell lines. The use of cell lines
      with defined metabolic capabilities seems to be a valuable tool to study specific
      metabolic pathways important in the activation of procarcinogens.

PMID- 7527493
TI  - A comparison of transurethral surgery with watchful waiting for moderate symptoms
      of benign prostatic hyperplasia. The Veterans Affairs Cooperative Study Group on
      Transurethral Resection of the Prostate.
AB  - BACKGROUND: Transurethral resection of the prostate is the most common surgical
      treatment for benign prostatic hyperplasia. We conducted a multicenter randomized
      trial to compare this surgery with watchful waiting in men with moderate symptoms
      of benign prostatic hyperplasia. METHODS: Of 800 men over the age of 54 years who
      were screened between July 1986 and July 1989, 556 (mean [+/- SD] age, 66 +/- 5
      years) were studied (280 in the surgery group and 276 in the watchful-waiting
      group). Patients' symptoms and the degree to which they were bothered by urinary
      difficulties were measured with standardized questionnaires and medical
      evaluations. The primary outcome measure was treatment failure, which was defined
      as the occurrence of any of the following: death, repeated or intractable urinary
      retention, a residual urinary volume over 350 ml, the development of bladder
      calculus, new and persistent incontinence, a high symptom score, or a doubling of
      the serum creatinine concentration. Patients were followed for three years.
      RESULTS: Of the men randomly assigned to the surgery group, 249 underwent surgery
      within two weeks after the assignment. Surgery was not associated with impotence
      or urinary incontinence. The average follow-up period was 2.8 years. In an
      intention-to-treat analysis, there were 23 treatment failures in the surgery
      group, as compared with 47 in the watchful-waiting group (relative risk, 0.48; 95
      percent confidence interval, 0.30 to 0.77). Of the men assigned to the watchful
      waiting group, 65 (24 percent) underwent surgery within three years after the
      assignment. Surgery was associated with improvement in symptoms and in scores for
      urinary difficulties and interference with activities of daily living (P < 0.001
      for all comparisons). The outcomes of surgery were best for the men who were most
      bothered by urinary symptoms at base line. CONCLUSIONS: For men with moderate
      symptoms of benign prostatic hyperplasia, surgery is more effective than watchful
      waiting in reducing the rate of treatment failure and improving genitourinary
      symptoms. Watchful waiting is usually a safe alternative for men who are less
      bothered by urinary difficulty or who wish to delay surgery.

PMID- 7527494
TI  - Benign prostatic hyperplasia. Medical and minimally invasive treatment options.

PMID- 7527495
TI  - Nitric oxide in skeletal muscle.
AB  - Reactive oxygen intermediates modulate skeletal muscle contraction, but little is
      known about the role of nitric oxide (NO). Here we show that rat skeletal muscle
      expresses neuronal-type NO synthase and that activity varies among several
      respiratory and limb muscles. Immunohistochemistry showed prominent staining of
      type II (fast) fibre cell membranes with antibodies against neuronal-type NO
      synthase. NO synthase activity in muscles correlated with type II fibre density.
      Resting diaphragm muscle produced detectable NO chi, but no reactive oxygen
      intermediates. In contrast, actively contracting muscle generated increased
      levels of reactive oxygen intermediates. Contractile function was augmented by
      blockers of NO synthase, extracellular NO chelation, and guanylyl cyclase
      inhibition; it was depressed by NO donors and by increased levels of cyclic GMP.
      Force-frequency plots of different muscles showed an inverse correlation between
      NO synthase activity and force development. Our results support two physiological
      functions of NO in skeletal muscle. The first is to promote relaxation through
      the cGMP pathway. The second is to modulate increases in contraction that are
      dependent on reactive oxygen intermediates and which are thought to occur through
      reactions with regulatory thiols on the sarcoplasmic reticulum.

PMID- 7527497
TI  - Antigen presentation. Chewing the fat.

PMID- 7527496
TI  - Activation of the kinase Pelle by Tube in the dorsoventral signal transduction
      pathway of Drosophila embryo.
AB  - The concentration of Dorsal protein in the nucleus determines cell fate along the
      dorsoventral axis of the Drosophila embryo. The dorsal-group genes and the cactus
      gene are required for production and transmission of a localized signal on the
      ventral side of the embryo which determines the position of the highest nuclear
      concentration of Dorsal protein. The ventralizing signal produced in somatic
      cells is transmitted through the perivitelline space to the integral membrane
      protein Toll. Inside the embryo it leads to dissociation of the cytoplasmic
      Dorsal-Cactus complex and subsequent nuclear localization of Dorsal protein. Two
      components are known to mediate the signal transduction between Toll and Dorsal
      Cactus: Pelle, a serine/threonine protein kinase, and Tube, a protein with an
      unknown biochemical activity. Here we construct gain-of-function alleles of pelle
      and tube and show that pelle functions downstream of tube. In addition, Pelle and
      Tube interact directly with one another. We propose that Tube is a direct
      activator of the protein kinase Pelle.

PMID- 7527498
TI  - Unexpected activity of saporins.

PMID- 7527499
TI  - Replication step.

PMID- 7527500
TI  - Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells.
AB  - Major histocompatibility complex (MHC) class I and class II molecules bind
      immunogenic peptides and present them to lymphocytes bearing the alpha beta T
      cell antigen receptor (TCR). An analogous antigen-presenting function also has
      been proposed for the non-MHC-encoded CD1 molecules, a family of non-polymorphic,
      beta 2-microglobulin-associated glycoproteins expressed on most professional
      antigen-presenting cells. In support of this hypothesis, CD1 molecules are
      recognized by selected CD4-CD8- alpha beta or gamma delta TCR+ T-cell clones, and
      we have recently shown that CD1 molecules restrict the recognition of foreign
      microbial antigens by alpha beta TCR+ T cells. But the substantial structural
      divergence of CD1 from MHC class I and class II molecules, raises the possibility
      that the antigens presented by the CD1 system may differ fundamentally from those
      presented by MHC-encoded molecules. Here we report that a purified CD1b
      restricted antigen of Mycobacterium tuberculosis presented to alpha beta TCR+ T
      cells is mycolic acid, a family of alpha-branched, beta-hydroxy, long-chain fatty
      acids found in mycobacteria. This example of non-protein microbial antigen
      recognition suggests that alpha beta TCR+ T cells recognize a broader range of
      antigens than previously appreciated and that at least one member of the CD1
      family has evolved the ability to present lipid antigens.

PMID- 7527502
TI  - Effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane
      ionic currents and action potentials of guinea-pig ventricular cells.
AB  - We examined the effects of cibenzoline, a new class Ia antiarrhythmic drug, on
      various membrane ionic currents and action potentials of guinea-pig single
      ventricular cells, using patch clamp techniques in whole-cell configuration.
      Action potentials and the membrane currents were evoked at a clamping rate of 0.2
      Hz, and all experiments were performed at 32-33 degrees C. 1) Cibenzoline (5, 10
      and 30 microM) decreased the Na+ current (INa), in a concentration-dependent
      manner. The concentration of the half-maximal inhibition (Kd) for INa was
      estimated to be 7.8 microM. 2) In addition to the inhibition of INa, this drug
      (5, 10, and 30 microM) decreased, in a concentration-dependent manner, all other
      membrane currents examined, such as L-type Ca2+ current (ICa), delayed rectifier
      K+ current (IK), and inward rectifier K+ current (IK1). The Kd (apparent
      dissociation constant) values were 14.4 microM for ICa, 23.0 microM for IK, and
      33.7 microM for IK1 respectively. 3) Cibenzoline (5, 10, and 30 microns)
      significantly shortened the action potential duration measured at both 30% and
      90% repolarization without altering the resting membrane potential. From these
      findings, we conclude that apart from potent inhibitory effects on INa,
      cibenzoline possesses multiple blocking effects on other currents, e.g., ICa, IK
      and IK1, with a different potency (INa > ICa > IK > IK1) and with essentially the
      same efficacy. These effects may explain, at least in part, the alleged, potent
      antiarrhythmic effects of this drug.

PMID- 7527503
TI  - Histone-reactive IgA antibodies in adult IgA nephropathy and other primary
      glomerulonephritis.
AB  - The levels of histone-reactive IgA antibodies in the sera of adult patients with
      IgA mesangial glomerulonephritis, membranous glomerulonephritis,
      membranoproliferative glomerulonephritis and idiopathic nephrotic syndrome
      (minimal change disease+segmental glomerulosclerosis+IgM nephropathy) were
      evaluated by an enzyme-linked immunosorbent assay. Increased levels of IgA
      antibodies to all five major histones (H1, H2A, H2B, H3, H4) were found in all
      four disease groups when compared to normal controls. These histone-reactive IgA
      antibodies were restricted to the IgA1 subclass and their levels did not
      correlate with the levels of total serum IgA, nor with serum creatinine,
      creatinine clearance, and 24-hour proteinuria. Increasing ionic strength resulted
      in only partial inhibition of the binding to histones and, in individual
      patients, levels of reactivity with individual histones were usually correlated.
      This study shows that elevated levels of IgA antibodies reactive with self
      antigens are present in primary glomerulonephritis and extends previous
      observations indicating that anomalies of the IgA system occur in various forms
      of primary glomerulonephritis and are not limited to IgA nephropathy.

PMID- 7527501
TI  - Role of serotonin in the anticonvulsant effect of fluoxetine in genetically
      epilepsy-prone rats.
AB  - This study was designed to demonstrate a role of serotonin in the anticonvulsant
      effect of fluoxetine, a serotonin reuptake inhibitor, in genetically epilepsy
      prone rats. When varied doses of 5-hydroxytryptophan (12.5, 25, 50 mg/kg) were
      administered i.p. along with a fixed dose of fluoxetine (15 mg/kg) to severe
      seizure genetically epilepsy-prone rats, the severity of audiogenic seizures was
      decreased dose-dependently, and the combination treatment also produced a marked
      potentiation of the anticonvulsant effect when compared with administration of
      either drug alone. Pretreatment of severe seizure genetically epilepsy-prone rats
      with p-chlorophenylalanine depleted brain serotonin and reduced the
      anticonvulsant effectiveness of fluoxetine. By using intracerebral microdialysis,
      the depletion of serotonin after p-chlorophenylalanine treatment was confirmed by
      measuring thalamic extracellular serotonin and 5-hydroxyindoleacetic acid
      concentrations during basal release and in response to a challenge dose of
      fluoxetine. We concluded that serotonergic transmission may be involved in the
      anticonvulsant effect of fluoxetine in severe seizure genetically epilepsy-prone
      rats.

PMID- 7527505
TI  - Ophthalmic features of fourteen cases of Goodpasture's syndrome.
AB  - Juxtapapillary subretinal neovascular membranes developed in both eyes of a
      patient who had been treated for Goodpasture's syndrome for 4 years. These
      lesions caused visual impairment but were successfully treated by laser
      photocoagulation. Subretinal neovascularisation has not been reported before in
      association with Goodpasture's syndrome, but diverse ocular abnormalities have
      been described. It is not certain whether these lesions were caused by anti
      basement-membrane auto-antibodies. The eyes of 13 other patients with
      Goodpasture's syndrome were examined, in order to detect other unsuspected ocular
      pathology. In 1 further patient, both retinae contained a few unexplained
      superficial retinal haemorrhages. During follow-up, the original patient
      developed bilateral peripheral retinoschisis. From this short series and from
      cases previously described, we conclude that sight-threatening ocular
      abnormalities are rare in Goodpasture's syndrome. It is, however, particularly
      important to be aware of the possibility of treatable eye disease in
      Goodpasture's syndrome, since the introduction of effective treatment with
      immunosuppression and plasmapheresis has made long-term survival likely.

PMID- 7527504
TI  - Persistence of antibodies to hepatitis C virus in a chronic hemodialysis
      population.
AB  - In order to evaluate the persistence of antibodies against hepatitis C virus
      (HCV) in a chronic hemodialysis population, we studied 151 HBsAg-negative
      patients. Anti-HCV titers were evaluated every 3 months over 1 year, and the
      serum alanine aminotransferase/serum aspartate aminotransferase ratio monthly
      from the start of hemodialysis. The anti-HCV titers (ELISA C100-3) remained
      stable in 127 patients and fluctuated in 24, without an evident correlation with
      hepatic function. Using our criteria, we found 85 patients with non-A, non-B
      hepatitis, 57 of them with biochemical criteria of chronic hepatic disease. There
      was a strong correlation between antibodies to HCV and non-A, non-B hepatitis
      (chi 2; p < 0.05) which was more marked in those patients with biochemical
      criteria of chronic hepatic disease (chi 2; p < 0.001). We concluded that the
      anti-HCV titer is reliable as a long-term marker of hepatitis C virus infection.

PMID- 7527506
TI  - Immunohistochemical studies of vitronectin, C5b-9, and vitronectin receptor in
      membranous nephropathy.
AB  - To investigate the involvement of vitronectin, the terminal complement complex
      (C5b-9), and the vitronectin receptor in the pathogenesis of membranous
      nephropathy, the immunohistochemical localization of these antigens in the kidney
      was determined using the immunoperoxidase method and monoclonal antibodies:
      antivitronectin, anti-SC5b-9 (neoantigen), and antivitronectin receptor (specific
      for alpha v beta 3 and alpha v). The subjects were 6 patients with membranous
      nephropathy, and the controls were 2 patients with minimal-change nephrotic
      syndrome. In membranous nephropathy, vitronectin was localized in subepithelial
      deposits and in epithelial cell foot processes and was intensely positive in the
      foot processes adjacent to subepithelial deposits. C5b-9 showed a similar pattern
      of localization to vitronectin. Both alpha v beta 3 and alpha v were localized in
      the basal portions of the foot processes of visceral epithelial cells as well as
      along the borders of these cells adjacent to the urinary space. Deposition at the
      former site was heavier than at the latter, and localization was especially
      prominent adjacent to the subepithelial deposits. In addition, alpha v was
      localized around and within some of the electron-lucent subepithelial deposits in
      the basement membrane. In contrast, the deposition of vitronectin, C5b-9, alpha v
      beta 3, and alpha v was always less intense in minimal-change nephrotic syndrome
      than in membranous nephropathy. Vitronectin and C5b-9 were localized to small
      parts of mesangium and glomerular basement membrane, while alpha v beta 3 and
      alpha v deposits showed no difference in intensity between the basal portions of
      the foot processes and the urinary border of the visceral epithelial cells. Thus,
      membranous nephropathy featured increased localization of vitronectin, C5b-9, and
      vitronectin receptors both within and around the subepithelial deposits,
      suggesting that the mechanism of immune complex disposal via the vitronectin
      receptor and the vitronectin-C5b-9 complex, associated with complement activation
      due to subepithelial immune complex formation, may also be active.

PMID- 7527507
TI  - Coronary vascular and myocardial effects of substance P in hypercholesterolemic
      rabbits.
AB  - Age-matched male New Zealand white rabbits (n = 16) were allocated to two groups:
      group 1 (n = 8) received a standard rabbit diet; group 2 (n = 8) received a 2%
      cholesterol-enriched diet. After 8 weeks of prescribed diet, hearts were excised
      and placed on a constant perfusion pressure Langendorff-type apparatus. Coronary
      flow, left ventricular pressure, and isovolumic dP/dt were continuously measured.
      Baseline recordings were made and then a single 5 nmol bolus dose of substance P
      was delivered into the coronary perfusate. Mean serum cholesterol levels in group
      1 were 53 +/- 17 (SEM) mg.dl-1, in group 2 1438 +/- 143 mg.dl-1. In group 1, the
      injection of substance P caused mean coronary flow to increase 39 +/- 6%, mean
      coronary vascular resistance to decrease 28 +/- 3%, and mean dP/dt to increase 11
      +/- 4%. In group 2, coronary flow increased 57 +/- 13%, coronary vascular
      resistance decreased 33 +/- 5%, and dP/dt increased 17 +/- 4%. Within groups,
      values changed significantly from baseline but these changes were not
      significantly different between groups. The duration of coronary flow response
      was 113 +/- 20 s in group 1 and 63 +/- 8 s in group 2. Substance P is a potent
      dilator of coronary resistance vessels and has positive inotropic effects in the
      rabbit. High levels of cholesterol exposure do not alter the magnitude of
      substance P-induced vasodilation, but the duration of the response is shortened.

PMID- 7527508
TI  - Serial analysis of circulating adhesion molecules and TNF receptor in serum from
      patients with multiple sclerosis: cICAM-1 is an indicator for relapse.
AB  - We determined the serum levels for circulating adhesion molecules (circulating
      intercellular adhesion molecule-1 [cICAM-1], circulating endothelial leukocyte
      adhesion molecule-1 [cELAM-1], and circulating L-selectin [cL-selectin]) and
      circulating tumor necrosis factor receptor (cTNF-R) p60 in 29 patients with
      relapsing-remitting MS serially over a period of 12 months. During this period
      there were 27 relapses in 14 patients (48%). There was progression of disease
      activity in 12/25 patients (48%), as assessed by the occurrence of new lesions on
      nonenhancing, T2-weighted MRIs of the head. Clinically active patients with
      relapse or disease progression on MRI (n = 18) had frequent fluctuations in their
      serum levels for cICAM-1 if compared to patients with stable MS (n = 11). There
      were significant differences in the cumulative cICAM-1 production between the two
      groups (502 +/- 218 ng/ml in active versus 225 +/- 82 ng/ml in stable MS
      patients; p < 0.001). cTNF-R p60 serum levels were higher in patients with stable
      compared to active disease (2.3 +/- 0.5 ng/ml versus 1.5 +/- 0.6 ng/ml; p <
      0.005). A significant increase in cICAM-1 levels was present at the time of a
      relapse (799 +/- 263 ng/ml versus 449 +/- 95 ng/ml; p < 0.001), whereas the
      highest serum levels for cTNF-R p60 occurred 4 weeks after the onset of a relapse
      (1.8 +/- 0.5 ng/ml at relapse versus 2.3 +/- 0.6 ng/ml 4 weeks after a relapse; p
      < 0.01). Interestingly, the cL-selectin serum levels in all MS patients were
      significantly higher than in healthy donors, whereas there were no differences
      for cELAM-1. These results reflect distinct changes of inflammatory variables in
      serum of patients with MS and revealed that cICAM-1 is an indicator for disease
      activity and that high serum levels for cTNF-R p60 are associated with remission.

PMID- 7527509
TI  - Accumulation of the p53 tumor-suppressor gene product in oral leukoplakia.
AB  - OBJECTIVES: (1) To determine whether the protein of the suppressor gene p53
      accumulates in leukoplakia of the oral cavity in individuals who use snuff; and
      (2) to determine whether a correlation exists between the accumulation of p53
      protein and the degree of epithelial dysplasia present in oral leukoplakia.
      DESIGN: Retrospective analysis of archival tissue specimens. SETTING: The
      University Hospital, a tertiary referral hospital affiliated with the Oklahoma
      University Medical Center, Oklahoma City, Oklahoma. PATIENTS: In the first part
      of the study, biopsy specimens of leukoplakia from 12 persons who used snuff were
      compared with specimens from uninvolved oral mucosa of the same persons and with
      biopsy specimens from 12 nontobacco-using persons. In the second part of the
      study, accumulation of p53 protein was determined in 42 archival paraffin
      embedded specimens from oral leukoplakia and correlated with the degree of
      epithelial dysplasia. METHODS: Accumulation of p53 protein was assessed by
      immunoperoxidase staining with four different primary antibodies. Positive cells
      were counted in five consecutive high-power fields. RESULTS: In part one, the
      average number of positive cells in the leukoplakia of snuff-users (21.89 +/-
      4.33; mean +/- SE) was higher than that of normal-appearing mucosa (4.00 +/- 1.0;
      p < 0.05) and that of nontobacco-using controls (7.00 +/- 5.04). In part two, the
      average number of positive cells was higher in the moderately dysplastic (140.36
      +/- 30.03) and severely dysplastic lesions (232.86 +/- 26.85) than in the mildly
      dysplastic lesions (14.53 +/- 3.33; p < 0.05). The correlation between the degree
      of epithelial dysplasia and the number of cells positive is strong (Spearman's
      correlation coefficient = 0.853). CONCLUSIONS: The accumulation of p53 protein in
      leukoplakia of snuff-users is higher than in normal-appearing oral mucosa from
      both snuff-users and nontobacco-using controls. A strong correlation exists
      between the degree of epithelial dysplasia present in oral leukoplakia and the
      number of cells staining positive for p53. The accumulation of p53 protein holds
      potential as an intermediate end point in studies of chemoprevention of oral
      cancer.

PMID- 7527510
TI  - Epinephrine-induced ventricular fibrillation during anesthesia for myringotomy
      and tube insertion.

PMID- 7527511
TI  - Epinephrine hypersensitivity-induced cardiovascular crisis in otologic surgery.

PMID- 7527512
TI  - The use of the APAAP technique as a rapid indicator of peripheral blood
      progenitor cell levels.
AB  - Rapid and sustained engraftment following autotransplantation with peripheral
      blood stem cells (PBSC) depends on adequate numbers of stem cells and progenitor
      cells. In this study we have compared the number of myeloid progenitor cells
      quantitated using the colony forming units-granulocyte macrophage (CFU-GM)
      clonogenic assay with the number of CD34+ cells estimated both by flow cytometry
      and by the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. We
      have analysed 15 peripheral blood mononuclear cells (PBMNC) samples from 13
      normal subjects and 179 PBMNC from 32 patients undergoing PBSC harvests during
      the recovery phase of high dose cyclophosphamide chemotheraphy. The number of
      CD34+ cells measured by the APAAP technique correlated well with the number of
      CD34+ cells measured by flow cytometry (r = 0.727, p = 0.0001), and also with the
      number of CFU-GM measured in the clonogenic assay (r = 0.721, p = 0.0001). The
      APAAP method provides a rapid, reliable measure of progenitor cell levels that
      can be used to monitor the optimal time to harvest peripheral blood stem cells
      (PBSC), and to estimate the marrow repopulating ability (MRA) of stem cell
      preparations used for transplantation.

PMID- 7527513
TI  - Pseudomonas cepacia in the sputum of cystic fibrosis patients.
AB  - Colonization of sputum by Pseudomonas cepacia has been associated with
      progressive respiratory deterioration and a worsening prognosis for some cystic
      fibrosis patients. After laboratory methods were changed and a selective medium
      introduced, P. cepacia was isolated from the sputa of 16 out of 82 patients with
      cystic fibrosis attending this hospital: a prevalence rate of 20%. P. cepacia was
      found in the first sputum examined of 12 patients after the new methods were
      introduced, indicating that colonization was not necessarily a recent event. All
      isolates were satisfactorily identified using conventional media but half were
      identified with only a low level of confidence using the API 20NE kit. Further
      studies using adequate laboratory methods are required to determine the
      prevalence and significance of this organism in Australia.

PMID- 7527514
TI  - An evaluation of four methods for the detection of Pneumocystis carinii in
      clinical specimens.
AB  - We undertook a prospective evaluation of 4 methods for the detection of
      Pneumocystis carinii in clinical specimens and compared an indirect
      immunofluorescence assay (IFA) (Diagnostics Pasteur), and a fluorescent whitening
      agent (FWA) (Blankophor BA 267%, Bayer, Australia) with our standard methenamine
      silver (MeAg) and toluidine blue O (TB) stains. Two hundred and two specimens
      were received from 162 patients (133 HIV infected, 19 heart or heart-lung
      transplant recipients, and 10 "miscellaneous"). The specimens consisted of 132
      induced sputa, 56 bronchoalveolar lavage specimens, 10 fine needle aspiration
      lung biopsies, and 4 pleural fluid specimens. P. carinii was detected in 44 (22%)
      of the specimens. The sensitivities for the detection of P. carinii pneumonia
      were IFA: 92% (95% CI, 83-100%), FWA: 57% (95% CI, 41-73%), MeAg: 54% (95% CI, 38
      70%), and TB: 49% (95% CI, 33-65%). Discordant results were greatest in specimens
      from patients who were receiving specific anti-P. carinii prophylaxis, or who had
      received treatment for several days prior to sampling. IFA was the most sensitive
      test and relatively easy to perform. IFA was also the most expensive test. We
      found the FWA method a useful screening test as it is cheap and quick to perform.
      However, it is less sensitive than IFA, which should be performed on the negative
      specimens. With the increasing use of specific anti-P. carinii prophylaxis in HIV
      infected patients, methods more specific and sensitive than MeAg and TB stains
      are required. We have found IFA to improve significantly the rate of detection of
      P. carinii in this patient group.

PMID- 7527515
TI  - Knowledge of and attitudes towards children with special needs by selected
      groups.
AB  - To explore knowledge of and attitudes about children who have special needs, a
      questionnaire was submitted to 1145 persons (305 lyceum students, 94 teachers of
      secondary education, 247 medical students, 354 physical education students, and
      145 persons having an exceptional child in their families). Questions concerned
      the knowledge of categories of children with special needs, acceptance of them in
      regular classrooms, and willingness to work with them. Analysis showed that most
      people including teachers had limited awareness of exceptional children, their
      problems, education, and integration. They showed partial acceptance of
      mainstreaming and desire to work with such children. Careful education for all,
      especially teachers, seems advisable.

PMID- 7527516
TI  - Comparison of Vineland Adaptive Behavior Scales-Survey Form age equivalent and
      standard score with the Bayley Mental Development Index.
AB  - The Vineland Adaptive Behavior Scales-Survey Form standard score, Vineland
      Adaptive Behavior Scales-Survey Form age equivalent and Bayley scales' Mental
      Development Index were given to 44 high-risk infants age 12 mo. and suspected of
      developmental delay. The VABS-Survey Form, a revision of the Vineland Social
      Maturity Scale is frequently used in assessment of developmental delay; however,
      questions have arisen as to whether the standard score or age equivalent is the
      better measure. A developmental quotient based on VABS-SF age equivalent and VABS
      SF standard score was compared with the Bayley Mental Development Index. The mean
      VABS-SF standard score was significantly higher than the age equivalent quotient
      and the Bayley Mental Development Index. Implications for the use of VABS-SF age
      equivalent in evaluating such infants are discussed.

PMID- 7527517
TI  - Common pediatric surgical problems.
AB  - Common pediatric surgical problems, including hernias, pyloric stenosis,
      intussusception, and appendicitis continue to present a challenge to the health
      care provider. Clinical presentation may be typical, may vary with age or signs
      and symptoms, or may be vague and inconclusive. Management of these problems may
      range from nonoperative to traditional surgical intervention. Nursing
      implications include counseling, patient and family education, pre- and
      postoperative care, and the prevention of complications.

PMID- 7527518
TI  - Pediatric trauma. An overview.
AB  - Trauma is the number one killer of children in the United States. A prerequisite
      for caring for injured children is a thorough understanding of the most common
      pediatric injuries, the pathophysiology involved, and the priorities of
      evaluation and treatment. Prevention remains the most effective way to manage
      trauma.

PMID- 7527520
TI  - Gastrointestinal bleeding in children. Implications for nursing.
AB  - Gastrointestinal (GI) bleeding is a common reason for a pediatric surgical
      consult. Nurses who care for children can gather important data in their patient
      assessments. An understanding of the cause, diagnosis, and management of select
      disease entities that result in GI bleeding will aid the nurse in the assessment
      and care of pediatric patients. This article provides an overview of these
      conditions.

PMID- 7527519
TI  - Solid tumors in children.
AB  - A thorough understanding of the incidence, clinical presentation, treatment,
      prognosis, and psychosocial issues surrounding children with solid tumors enables
      the nurse to actively participate on the health care team. Although significant
      advances over the past two-and-a-half decades to improve the outcomes of children
      with cancer have occurred, there remains room for continued improvement,
      especially among children with advanced-stage nephroblastoma, neuroblastoma, HCC,
      and teratoma.

PMID- 7527521
TI  - Advances in pediatric solid organ transplantation.
AB  - Thorough nursing assessment and intervention are necessary throughout the
      transplant period. As the demand and success of solid organ transplantation in
      the pediatric population grows, research in the area offers a bright future for
      transplantation. This has provided the impetus for changes in allocation policies
      such as providing extra points for pediatric renal transplant recipients and
      alternative surgical procedures, such as reduced liver grafts and living related
      donors. Currently, new immunosuppressant medications are being developed, which
      may decrease the incidence of rejection and produce fewer serious side effects
      than medications presently in use.

PMID- 7527523
TI  - Caring for children with ostomies.
AB  - Caring for children with ostomies comprehensively requires that the healthcare
      professional understand issues related to normal growth and development as well
      as more specific medical information about disease processes and ostomy care.
      Parents should have a working knowledge of routine ostomy care and need
      guidelines to assist them in recognizing ostomy complications. Complications
      range from mild to severe. Many patients will experience at least one ostomy
      related complication during the time they have their diversion. Active support of
      the child and the parent is essential toward facilitating acceptance and
      integration of ostomy care in pediatric ostomy clients.

PMID- 7527522
TI  - Surgical intervention in children with HIV infection.
AB  - AIDS is a complex disease with variable manifestations. Effective care can
      significantly impede the progression of this disease. Understanding the
      complexities of this illness allows nurses to develop an appropriate plan of care
      with sensitivity and acknowledgment of infected children's individual needs.
      Surgical intervention often is required for diagnosis and symptom management of
      AIDS-related conditions. With good preparation and postoperative care, surgical
      interventions can be a successful means of enhancing quality of life. In our
      institution, the pediatric nurse practitioner for infectious diseases and the
      clinical nurse specialist for pediatric surgery work together to manage the
      surgical issues of these children.

PMID- 7527524
TI  - Preparation for surgery and adjustment to hospitalization.
AB  - One of every four children will be hospitalized at least once before reaching
      school age. The physical and psychosocial stress of hospitalization may be
      influenced by the child's developmental level, causing behavioral changes,
      somatic complaints, and a prolonged hospital stay. Through the use of careful
      development assessments, preoperative tours, and therapeutic play techniques
      fears can be allayed, misconceptions corrected, emotionally charged issues
      addressed, and a positive self-image created.

PMID- 7527525
TI  - Pediatric laparoscopy and thoracoscopy.
AB  - Although applications of MIS to the pediatric population appear limitless, it is
      important to continually assess what surgical procedure is in the best interest
      of the individual child. The pediatric expertise of the surgeon,
      anesthesiologist, and nursing staff along with their comfort with MIS should be
      thoroughly considered. The management of available resources also is of
      importance. The experimental techniques of today are rapidly becoming tomorrow's
      established standard of care. All health professionals should take the
      responsibility of developing expertise with these new techniques. The challenge
      of the future is appropriate application of these procedures while maintaining
      the child's safety as the foremost concern.

PMID- 7527526
TI  - The unborn surgical patient. A nursing frontier.
AB  - The fetus can now be considered a patient. Sophisticated imaging techniques and
      prenatal tests have allowed precise diagnosis of fetal abnormalities. Subsequent
      recommendations for treatment are evolving depending on diagnosis and progression
      of disease. For severely affected fetuses with life-threatening problems, fetal
      surgery is a proposed intervention. Knowledge of the diagnosis and potential
      treatment modalities are now a prerequisite for providing the necessary support
      and care of mothers of fetuses with an anomaly. The fetal treatment center
      provides a regionalized approach to providing specialized care to the mother
      carrying a fetus with an anomaly. The center provides both prenatal and postnatal
      diagnosis; treatment; and obstetric, neonatal, and pediatric surgical management
      for a wide variety of pediatric surgical disorders. The fetal treatment center
      model is a useful one offering knowledgeable, coordinated, efficient, and
      compassionate care to parents facing difficult decisions regarding their unborn
      child. Future interventions include less invasive procedures to the mother, such
      as videofetoscopic techniques. Use of new research related to scarless wound
      healing may allow endoscopic techniques to correct cleft lips in utero. Gene and
      stem cell therapy in utero may ameliorate blood disorders, enzyme deficiencies,
      hemoglobinopathies, and so on prior to birth. Finally, other lethal fetal
      anomalies, such as pulmonary atresia and laryngeal atresia may also benefit from
      in utero intervention.

PMID- 7527527
TI  - Color Doppler imaging of modified Blalock-Taussig shunts during infancy.
AB  - To assess the role of color Doppler echocardiography in the early postoperative
      evaluation of patients with a Blalock-Taussig shunt we examined 13 consecutive
      infants who underwent insertion of either a modified right (6 patients) or a
      modified left (7 patients) Blalock-Taussig shunt (age range 7 days to 6 months,
      mean age 8 weeks). Examination of the patients in a high parasternal right or
      left long axis was able to determine patency of the shunt in 12 patients. In the
      remaining patient, who did not show flow in the shunt, complete occlusion of the
      shunt was confirmed by angiography. From subcostal views we were able to
      demonstrate patency of the shunt in 75% of the infants and in all patients
      younger than 4 weeks of age. In our experience color Doppler echocardiography is
      a highly reliable method for early postoperative evaluation of infants with a
      Blalock-Taussig shunt.

PMID- 7527528
TI  - Neurokinin A coexists with substance P and serotonin in ventral medullary
      spinally projecting neurons of the rat.
AB  - The coexistence of neurokinin A (NKA) with substance P (SP) and serotonin (5-HT)
      in ventral medullary neurons of the parapyramidal region and nucleus raphe
      pallidus of the rat was studied using multiple immunofluorescence labeling.
      Nearly all of the NKA-immunoreactive (IR) cells in the parapyramidal region and
      raphe pallidus were SP-IR nd 5-HT-IR, whereas about 70% of the SP-IR neurons and
      about 60% of the 5-HT-IR neurons contained NKA-IR. There were no apparent
      differences in the patterns of coexistence between parapyramidal and raphe
      pallidus neurons. NKA-IR neurons, which colocalized SP-IR and 5-HT-IR, were
      studied for projections to the lumbar and thoracic spinal cord by use of
      retrograde transport of fluorescent tracer. Whereas about 50% of the retrogradely
      labeled neurons of the parapyramidal region and raphe pallidus contained NKA-IR,
      nearly all of the NKA-IR neurons projected to the thoracic and lumbar spinal
      cord. In addition, some NKA-IR neurons in the ventral medulla were retrogradely
      labeled with tracer from localized injections into the thoracic intermediolateral
      cell column. In summary, this study demonstrated that NKA-IR is colocalized with
      SP-IR in bulbospinal serotonergic neurons of the parapyramidal region and raphe
      pallidus, which are known to regulate sensory, motor, and autonomic activities of
      the spinal cord.

PMID- 7527529
TI  - CCK antagonists reveal that CCK-8 and JMV-180 interact with different sites on
      the rat pancreatic acinar cell CCKA receptor.
AB  - The ability of CCKA antagonists to inhibit full and partial CCK agonists of the
      rat pancreatic acinar cell CCKA receptor has been studied. When isolated rat
      pancreatic acini were superfused with CCK-8 (10 pM-1 nM) or CCK-4 (1 microM), an
      increase in [Ca2+]i signal was initiated. Concurrent superfusion of either L
      364,718 (0.1 microM) or lorglumide (10 microM), chemically distinct, specific,
      potent antagonists of the CCKA receptor, resulted in a rapid inhibition of the
      [Ca2+]i signal initiated by all concentrations of CCK-8. In contrast, Ca2+
      oscillations, initiated by JMV-180 (25 nM-1 microM), a partial agonist analogue
      of CCK-8, were essentially unaffected by concurrent superfusion of either L
      364,718 or lorglumide. When JMV-179, an analogue of JMV-180 that exhibits
      characteristics of a pure antagonist, was superfused concurrently with either CCK
      8 or JMV-180, Ca2+ oscillations were inhibited, even in the presence of 0.1
      microM L-364,718. In a similar fashion, amylase secretion stimulated by CCK-8 was
      markedly attenuated by L-364,718, lorglumide, and JMV-179, whereas secretion
      stimulated by JMV-180 was only inhibited by JMV-179. A model is proposed to
      reconcile this data, based on the assumption that JMV-180 and CCK-8 interact with
      discrete sites on the CCKA receptor, which are differentially affected by the
      binding of antagonists. This model may also explain how a single receptor may
      transduce multiple signals in response to different agonists.

PMID- 7527530
TI  - Four cross-linked HIV Gag peptides prime the immune response to HIV proteins in
      mice.
AB  - The functional help provided by four cross-linked synthetic peptides from HIV-1
      Gag structural proteins was investigated in the mouse model. These peptides,
      selected upon non-self-criteria, are not predicted as T epitopes by classical
      prediction methods such as the Rothbard consensus or the amphipathy rule. Priming
      mice with these peptides allows the enhancement of the antibody response to HIV-1
      Gag proteins (p55, p18, p24) given in the viral particle form. Furthermore, all
      of them also induce spleen and lymph node cells from primed mice to proliferate
      in vitro, in a MHC class II restricted context. This approach may help to
      identify relevant immunogenic viral epitopes that may be involved in a vaccinal
      strategy.

PMID- 7527531
TI  - Purification and characterization of galanin from the phylogenetically ancient
      fish, the bowfin (Amia calva) and dogfish (Scyliorhinus canicula).
AB  - Galanin was purified to near homogeneity from an extract of the stomachs of the
      holostean fish, the bowfin and the elasmobranch fish, the European common
      dogfish. Bowfin galanin contains an alpha'-amidated C-terminal residue and the
      primary structure of the peptide (GWTNL SAGYL LGPHA VDNHR SLNDK HGLA) shows only
      four amino acid substitutions (Val16-->Ile, Leu22-->Phe, Asn23-->His, and His26-
      >Tyr) compared with pig galanin. Dogfish galanin was isolated in a truncated form
      for which amino acid sequence was identical to residues (1-20) of bowfin galanin.
      The isolation of this fragment is indicative of processing at the site of a
      single arginyl residue, and an analogous peptide has been previously isolated
      from human intestine. The data demonstrate that peptides with close structural
      similarity to mammalian galanins are present in the gastrointestinal tracts of
      phylogenetically ancient fish.

PMID- 7527533
TI  - Lendrum (-MSB) staining for fibrin identification in sealed skin grafts.
AB  - The significance and effect of fibrin sealant systems for woundhealing are still
      unknown, because of the use of insufficient, conventional staining methods for
      the demonstration of the fibrin components used by sealant systems. From 21
      patients with extensive burns of 2nd and 3rd degree biopsies of the skin were
      obtained during consecutive operations to cover the defect of the skin with split
      thickness skin grafting. In the present paper morphological results concerning
      the demonstration of fibrin components and morphological differences in
      woundhealing of sealed and unsealed skin grafts are presented using Lendrum (
      MSB) staining. With this staining method it is possible to identify exogenous
      fibrin components of the sealant system and to differentiate between fresh and
      older fibrin components, due to colour changes depending on time.

PMID- 7527532
TI  - Novel soluble, high-affinity gastrin-releasing peptide binding proteins in Swiss
      3T3 fibroblasts.
AB  - Swiss 3T3 cells contained substantial amounts of soluble and specific [125I]GRP
      binders. Like the membrane-associated GRP receptor, they were of high affinity,
      saturable, bound to GRP(14-27) affinity gels, and exhibited specificity for
      GRP(14-27) binding. They differed in that acid or freezing destroyed specific
      binding, specific binding exhibited different time and temperature effects, no
      detergent was required for their solubilization, ammonium sulfate fractionation
      yielded different profiles, the M(rs) were lower, GRP(1-16) also blocked binding,
      and a polyclonal anti-GRP receptor antiserum did not bind on Western blots. The
      isolated, soluble GRP binding protein(s) rapidly degraded [125I]GRP. These
      soluble GRP binding proteins may play a role in the regulation of the mitogenic
      effects of GRP on these cells.

PMID- 7527534
TI  - Histogenetic consideration of ovarian sex cord-stromal tumors analyzed by
      expression pattern of cytokeratins, vimentin, and laminin. Correlation studies
      with human gonads.
AB  - A total of 30 sex cord-stromal tumors including 9 adult type and 5 juvenile type
      granulosa cell tumors (GCTs), 4 Sertoli-Leydig cell tumors (SLTs), 1
      gynandroblastoma, 5 thecomas, 2 fibromas and 3 sclerosing stromal tumors were
      immunohistochemically evaluated by means of cytokeratins of different molecular
      weight, vimentin and laminin with regard to the histogenesis of these tumors and
      to the embryogenesis of the sex cord and stroma of developing gonads. For
      comparison, 7 embryonic gonads, 9 fetal and 9 adult ovaries, 14 fetal and 5
      postnatal testes, and 1 gonadoblastoma were also examined. The coelomic
      epithelium of all gonads were positive for both cytokeratins (CAM 5.2 and AE1)
      and vimentin. In fetal ovaries, the granulosa cells of primordial follicles
      express low molecular weight cytokeratins only and those cells of more maturing
      follicles did not express any cytokeratin or vimentin. In adult ovaries, the
      granulosa cells of primordial follicles coexpressed low molecular weight
      cytokeratins and vimentin, but those cells of more maturing follicles expressed
      vimentin only. In fetal testes before 20 weeks gestational age, the Sertoli and
      Leydig cells did not express any cytokeratins and vimentin. After that time, both
      cells expressed vimentin only throughout life. The rete ovarii and rete testis
      from fetal to adult life coexpressed both low molecular weight cytokeratins and
      vimentin. The rete ovarii in all ages and rete testis in prenatal and childhood
      ages were surrounded by the laminin-positive basement membrane, however, the rete
      testis in adult were not. In neoplasia, the GCTs, thecomas, fibromas, and
      sclerosing stromal tumors expressed vimentin only.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7527535
TI  - Benign glandular peripheral nerve sheath tumor. A case report.
AB  - The glandular peripheral nerve sheath tumor is a rare variant of nerve sheath
      neoplasms in which the focally occurring glands are lined by cells showing
      divergent differentiation. The vast majority of the reported nerve sheath tumors
      harboring these glands have been malignant. We herein present a case of benign
      glandular peripheral nerve sheath tumor in a 43-year-old woman who had no
      evidence of von Recklinghausen's disease. Histologically, the tumor is composed
      of spindle cell component and collections of glandular component. The glandular
      component occupied the central two-thirds of the lesion and was lined by a single
      layer of nonciliated cuboidal or columnar cells. No mitotic figures were
      recognized in the spindle cell area. This spindle cell area had neurofibroma-like
      features rather than schwannoma. Many of the spindle cells had positive reaction
      products for S-100 protein. The glandular lining epithelium were positive for
      cytokeratins (CAM 5.2, AE1/AE3, PKK1) and EMA. Some epithelial cells were
      immunoreactive for CEA, chromogranin, somatostatin and Leu-7. These
      immunohistochemical findings support the neuroendocrine differentiation of the
      epithelial element from the schwannian component.

PMID- 7527539
TI  - Prenatal diagnosis of Klippel-Trenaunay-Weber syndrome by ultrasound.
AB  - Ultrasound examination due to an elevated maternal serum alpha-fetoprotein level
      showed lower extremity asymmetry. The findings were felt to be consistent with
      Klippel-Trenaunay-Weber syndrome. The pregnancy was terminated based on these
      findings. The ultrasound findings, confirming post-mortem examination, and
      counselling issues are discussed.

PMID- 7527537
TI  - Four-marker serum screening for Down's syndrome.
AB  - The value of measuring the separate sub-units of human chorionic gonadotrophin
      (free alpha-hCG and free beta-hCG) instead of total hCG together with alpha
      fetoprotein (AFP) and unconjugated oestriol (uE3) was examined to determine the
      effect on the performance of serum screening for Down's syndrome between 15 and
      22 weeks of pregnancy. The study was based on stored serum samples relating to 75
      singleton pregnancies with fetal Down's syndrome and 367 unaffected singleton
      pregnancies, matched for maternal age, gestational age, and duration of storage
      of the serum sample, supplemented by data from 970 white women with unaffected
      pregnancies. Using the four serum markers AFP, uE3, free beta-hCG, and free alpha
      hCG, in addition to maternal age, 65 per cent of Down's syndrome pregnancies were
      detected for a 5 per cent false-positive rate compared with 59 per cent with the
      conventional triple test (AFP, uE3, total hCG with maternal age). If gestation
      was based on an ultrasound scan examination, the detection rate was 72 per cent
      using the four serum markers compared with 67 per cent with the triple test. As
      an alternative illustration, if the detection rate was kept at 60 per cent and
      gestation was estimated by an ultrasound scan examination the four-marker test
      reduced the false-positive rate by one-third from 3 per cent using the triple
      test to 2 per cent with the four-marker test. Screening performance was hardly
      affected by adjusting marker levels for maternal weight.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7527538
TI  - Maternal serum free alpha-human chorionic gonadotrophin levels in twin
      pregnancies: implications for screening for Down's syndrome.
AB  - Maternal serum free alpha-human chorionic gonadotrophin (free alpha-hCG) levels
      were determined in twin and singleton pregnancies at 15-22 weeks of gestation
      using a set of stored serum samples relating to 200 twin pregnancies and 600
      singleton control pregnancies matched for gestational age and duration of
      storage. Free alpha-hCG values are, on average, 1.66 times greater in twin
      pregnancies than in singleton pregnancies (95 per cent confidence interval 1.56
      1.76). If maternal serum free alpha-hCG is used in screening for Down's syndrome,
      values in twin pregnancies can be adjusted using this result so that screening
      can be performed in twin pregnancies as well as in singleton pregnancies.

PMID- 7527540
TI  - Human maternal uniparental disomy for chromosome 16 and fetal development.
AB  - Two severely growth-retarded fetuses found to have maternal uniparental disomy
      (UPD) for chromosome 16 and trisomy 16 placental mosaicism both had an
      unfavourable outcome. Antenatally, the first case was complicated by an
      unexplained raised maternal serum alpha-fetoprotein concentration, preterm
      premature rupture of the membranes, and growth retardation detectable at 21
      weeks' gestation, whilst the other had an unexplained raised maternal serum human
      chorionic gonadotrophin level, a two-vessel cord on ultrasound, and cessation of
      growth at 25 weeks. At post-mortem, both babies had an imperforate anus. Fetal
      maternal UPD may explain the poor outcome that occurs in some cases of confined
      placental mosaicism for chromosome 16 and is also associated with specific fetal
      abnormalities.

PMID- 7527542
TI  - The mathematical basis for the increased sensitivity in cancer detection in air
      dried cytopreparations.
AB  - It is known that the volume of a sphere is 4/3 pi r3, the area of a circle is pi
      r2, and the nuclear volume remains constant even when a cell is flattened. The
      effect of air-drying that flattens a spherical nucleus with a radius of r to a
      discoid nucleus with an expanded radius of R and a thickness of T can be stated
      as follows: pi R2 = (4/3 pi r3)/T. Based on this formula, a graph was plotted to
      illustrate the effect of air-drying on the observed nuclear areas (ONA) of cells
      of various size. The ONA of ethanol-fixed Pap/H&E-stained cells or cells in
      tissue sections is pi r2; the ONA of air-dried Diff-Quik-stained cells is pi R
      (2), i.e., (4/3 pi r3)/T. The former follows a first-order straight line, and the
      latter follows a second-order curve. As a consequence, the subtle "nuclear size
      enlargement" and "broader nuclear size distribution" of low-grade cancer cells,
      detectable only by statistical analysis of the data obtained by an image analyzer
      in ethanol-fixed cytopreparations or in formaldehyde-fixed tissue sections,
      become augmented to such a degree on the air-dried Diff-Quik-stained preparations
      that they are easily detected by direct microscopic observation. In conclusion,
      the increased sensitivity in cancer detection in air-dried cytopreparations is
      due to the fact that the ONA of air-dried cells reflects nuclear volume.

PMID- 7527536
TI  - Value of maternal serum unconjugated oestriol measurement in prenatal screening
      for Down's syndrome.
AB  - We compared the medical and financial cost-effectiveness of prenatal serum
      screening for Down's syndrome using maternal age, serum alpha-fetoprotein and
      human chorionic gonadotrophin with and without the use of unconjugated oestriol.
      The use of unconjugated oestriol is medically more cost-effective than screening
      without it at all levels of detection. The actual performance depends on whether
      gestational age is estimated using 'dates' or an ultrasound scan. At a detection
      rate of 60 per cent, the proportion of unaffected fetal losses per case diagnosed
      at amniocentesis is about 22 per cent less if gestational age is estimated using
      dates (time since the first day of the last menstrual period) and about 47 per
      cent less if it is based on an ultrasound scan examination. At this detection
      rate, the inclusion of unconjugated oestriol increases costs by about 2k pounds
      per case diagnosed (36k pounds instead of 34k pounds) if gestational age is
      estimated using dates, but it is no more expensive if gestational age is measured
      from an ultrasound scan examination (indeed, it is more cost-effective at
      detection rates above 60 per cent). Since there is little change in the financial
      cost with the inclusion of unconjugated oestriol, for the improved medical
      performance of screening, it is worthwhile including it in the screening test.

PMID- 7527541
TI  - The multifocality of bronchioloalveolar lung carcinoma: evidence and implications
      of a multiclonal origin.
AB  - Bronchioloalveolar lung carcinoma (BAC) is a unique type of lung cancer with
      distinguishing pathologic, biologic, epidemiologic, and perhaps etiologic
      features that set it apart from all other forms of lung cancer, including general
      adenocarcinoma, into which it is traditionally grouped. Recent studies at our
      institution have demonstrated a near exponential increase in BAC cases with 25%
      showing evidence of multifocality. Although some theories suggest that this
      multifocality is caused by intrapulmonary aerosol/aspiration or lymphatic spread,
      this study provides evidence for multiclonality as the basis for some cases of
      multifocal BAC by exploiting a novel strategy for clonality determinations that
      involves polymerase chain reaction amplification of a 511-base pair region
      located within the first intron of the human hypoxanthine
      phosphoribosyltransferase gene, a site that contains inactive X chromosomal
      obligately methylated HpaII/MspI sites and single-base allelic polymorphisms in 5
      to 10% of females. BAC cells, obtained by enzymatic dissociation of different
      fresh/paraffin-embedded tumoral foci from polymorphic individuals with multilobar
      or bilateral BAC, were sorted to homogeneity with a fluorescein-conjugated
      anticarcinoembryonic antigen and then subjected to genomic DNA extraction and
      HpaII digestion before polymerase chain reaction amplification and subsequent
      analysis of the product on denaturing gradient gel electrophoresis. The differing
      migrations of the single homoduplexes generated were indicative of BAC clonal
      nonidentity or multiclonality in three separate cases. The demonstration of
      multiclonality in some cases of BAC provides an alternate explanation for
      multifocality.

PMID- 7527544
TI  - Toxicity of 5-aza-2'-deoxycytidine to mammalian cells is mediated primarily by
      covalent trapping of DNA methyltransferase rather than DNA demethylation.
AB  - The deoxycytidine analog 5-aza-2'-deoxycytidine (5-azadCyd) has been widely used
      as a DNA methylation inhibitor to experimentally induce gene expression and
      cellular differentiation. Prior to the availability of mutant mice with altered
      DNA methyltransferase levels, treatment of cells with drugs has been the only
      means to experimentally manipulate the level of genomic DNA methylation in
      mammalian cells. Substitution of DNA with 5-azadCyd leads to covalent trapping of
      the enzyme, thereby depleting the cells of enzyme activity and resulting in DNA
      demethylation. 5-AzadCyd or 5-azacytidine treatment causes multiple changes in
      treated cells, including activation of silent genes, decondensation of chromatin,
      and induction of cellular differentiation, all of which are believed to be
      consequences of drug-induced demethylation. 5-AzadCyd is highly toxic in cultured
      cells and animals and is utilized as a potent antitumor agent for treatment of
      certain human cancers. It has been postulated that the toxicity of the drug in
      mammalian cells is also due to its inhibition of DNA methylation. The chemistry
      of the methylation reaction is consistent, however, with an alternative
      mechanism: the cytotoxic effect of 5-azadCyd may be directly mediated through the
      covalent binding of DNA methyltransferase to 5-azadCyd-substituted DNA. We have
      tested this possibility by using embryonic stem cells and mice with reduced
      levels of DNA methyltransferase due to a targeted mutation of the gene. When
      exposed to 5-azadCyd mutant embryonic stem cells or embryos were significantly
      more resistant to the toxic effects of the drug than wild-type cells and embryos,
      respectively. These results strongly suggest that the cellular DNA
      methyltransferase itself, rather than the secondary demethylation of genomic DNA,
      is the primary mediator of 5-azadCyd cytotoxicity. In light of our results, some
      conclusions from previous studies using 5-azadCyd in order to experimentally
      manipulate cellular methylation levels may have to be reassessed. Also, our data
      make clear predictions for cancer treatment: tumor cells with elevated DNA
      methyltransferase levels would be expected to be susceptible to treatment with 5
      azadCyd, whereas tumors with reduced levels of the enzyme would be resistant.

PMID- 7527543
TI  - Hypermutagenesis of RNA using human immunodeficiency virus type 1 reverse
      transcriptase and biased dNTP concentrations.
AB  - The finding of G-->A hypermutated retroviral genomes in which up to 40% of
      guanines may be substituted by adenines was proposed to result from the depletion
      of the intracellular dCTP concentration and suggested a means to hypermutagenize
      nucleic acids. Using a RNA/reverse transcriptase ratio of approximately 1:30,
      comparable to that within the retroviral replication complex, G-->A hypermutants
      were produced in a simple in vitro reaction using highly biased dNTP
      concentrations--i.e., a low ratio of [dCTP]/[dTTP]. Up to 38% of G residues could
      be substituted, the proportion being inversely proportional to the concentration
      of dCTP. As G-->A hypermutation resulted from elongation beyond multiple rG.dT
      mismatches, U-->C hypermutants resulting from multiple rU.dG mismatches were
      sought, and found, during cDNA synthesis using low [dATP] and high [dGTP]. Mixed
      G-->A and U-->C hypermutants could also be produced under conditions of low
      [dCTP] plus low [dATP] and high [dTTP] plus high [dGTP]. Hypermutagenesis should
      allow jumping through, and subsequent exploration of, sequence space to a greater
      degree than heretofore and, in conjunction with genetic screening, might be of
      use in the search of proteins or ribozymes with novel or enhanced properties.

PMID- 7527545
TI  - The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5)
      are located on separate chromosomes in human, mouse, and rat.
AB  - The chromosomal localization of the human and rat genes encoding the kainate
      preferring glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5,
      respectively) was determined by Southern analysis of rat x mouse and human x
      mouse somatic cell hybrid panels and by fluorescence in situ hybridization. The
      localization of the mouse genes (Grik4 and Grik5) was established by
      interspecific backcross mapping. GRIK4 and GRIK5 are located on separate
      chromosomes (Chrs) in all species. GRIK4 mapped to human Chr 11q22.3, mouse Chr
      9, and rat Chr 8. GRIK5 mapped to human Chr 19q13.2, mouse Chr 7, and rat Chr 1.
      The genes encoding the (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA)-preferring subunit GluR4, or GluRD (GRIA4), the neural cell adhesion
      molecule (NCAM), the D2 dopamine receptor (DRD2), and the Thy-1 cell surface
      antigen (THY1) have all been previously mapped to the human Chr 11q22 region. The
      mapping of the human GRIK4 and GRIK5 genes confirms and extends the relationship
      between human Chr 11 and mouse Chr 9 and also human Chr 19 and mouse Chr 7. GRIK4
      is the fifth gene shared by human Chr 11 and rat Chr 8, whereas GRIK5 is 1 out of
      the 12 genes that are located on both human Chr 19 and rat Chr 1. Our data extend
      the conserved synteny established between certain human, mouse, and rat Chrs.

PMID- 7527546
TI  - Delineation and comparison of ganglioside-binding epitopes for the toxins of
      Vibrio cholerae, Escherichia coli, and Clostridium tetani: evidence for
      overlapping epitopes.
AB  - Binding studies of various glycolipids, mainly belonging to the ganglio series,
      to the toxins isolated from Vibrio cholerae, Escherichia coli, and Clostridium
      tetani have been performed, using the microtiter well assay. By using the found
      binding preferences in conjunction with minimum-energy conformations obtained
      from molecular modeling of the various ligands, binding epitopes on the natural
      receptor glycolipids for the toxins have been defined. The binding preferences
      for the cholera toxin and the heat-labile E. coli toxin are very similar, with
      the ganglioside GM1 being the most efficient ligand. The tetanus toxin binds
      strongly to gangliosides of the G1b series, with GT1b as the most efficient
      ligand. It is found that the binding epitope on GM1 for the cholera and heat
      labile toxins to a large extent overlaps with the epitope on GQ1b for the tetanus
      toxin.

PMID- 7527547
TI  - Voltage window for sustained elevation of cytosolic calcium in smooth muscle
      cells.
AB  - Action potentials activate voltage-dependent calcium channels and attendant
      increases in cytosolic calcium concentration ([Ca2+]i) in many excitable cells.
      The role of these channels in the regulation of [Ca2+]i in nonspiking cells that
      do not depolarize to membrane potentials sufficient to activate a substantial
      fraction of the available current is less clear. Measurements of the peak
      activation and steady-state inactivation of L-type calcium currents have
      predicted the existence of a noninactivating current window over a voltage range
      where channel inactivation is incomplete. The degree to which such small currents
      might regulate [Ca2+]i, however, has not been established. Here we demonstrate a
      "calcium window" in nondialyzed, quiescent smooth muscle cells over a small
      voltage range near the resting membrane potential. Sustained depolarizations in
      this voltage range, but not to more positive potentials, resulted in sustained
      rises in calcium, despite the fact that macroscopic inward currents were < 2 pA.
      The calcium window corresponded well with the predicted window current determined
      under the same conditions; the peak of the calcium window occurred at -30 mV,
      with steady-state rises in [Ca2+]i in some cells at -50 mV. Steady-state rises in
      [Ca2+]i following depolarization were completely blocked by nisoldipine and were
      augmented and shifted to more negative potentials by BAY K8644. Voltage-dependent
      calcium channels thus regulate steady-state calcium levels in nonspiking cells
      over a voltage range where macroscopic currents are only barely detectable. This
      voltage range is bounded at negative potentials by calcium channel activation and
      at more positive potentials by channel inactivation.

PMID- 7527549
TI  - Nitric oxide, cGMP, and hormone regulation of active sodium transport.
AB  - The inter- and intracellular regulator nitric oxide (NO) has been suggested to
      play a role in the modulation of cellular excitability, but the mechanism(s) by
      which this occurs remain unclear. Using the kidney as a model system, we report
      here evidence that NO, produced in response to various hormones and cytokines,
      can effect long-term alterations in the activity of the membrane sodium pump.
      This regulation of Na, K-ATPase, which occurs in a system of NO-containing renal
      tubules, involves cGMP and cGMP-dependent protein kinase. Na, K-ATPase can also
      be regulated by alterations of cGMP initiated through NO-independent factors,
      such as atriopeptin, and in nonrenal tissues, such as cerebellum. Regulation of
      the membrane sodium pump by NO and cGMP, therefore, represents a mechanism for
      hormonal modulation of ion gradients, not only in kidney but also in other
      organs, including brain, where NO and cGMP play a prominent role in cellular
      function.

PMID- 7527550
TI  - The nitric oxide/cyclic GMP pathway in organ transplantation: critical role in
      successful lung preservation.
AB  - Reestablishment of vascular homeostasis following ex vivo preservation is a
      critical determinant of successful organ transplantation. Because the nitric
      oxide (NO) pathway modulates pulmonary vascular tone and leukocyte/endothelial
      interactions, we hypothesized that reactive oxygen intermediates would lead to
      decreased NO (and hence cGMP) levels following pulmonary reperfusion, leading to
      increased pulmonary vascular resistance and leukostasis. Using an orthotopic rat
      model of lung transplantation, a porphyrinic microsensor was used to make direct
      in vivo measurements of pulmonary NO. NO levels measured at the surface of the
      transplanted lung plummeted immediately upon reperfusion, with levels moderately
      increased by topical application of superoxide dismutase. Because cGMP levels
      declined in preserved lungs after reperfusion, this led us to buttress the NO
      pathway by adding a membrane-permeant cGMP analog to the preservation solution.
      Compared with grafts stored in its absence, grafts stored with supplemental 8-Br
      cGMP and evaluated 30 min after reperfusion demonstrated lower pulmonary vascular
      resistances with increased graft blood flow, improved arterial oxygenation,
      decreased neutrophil infiltration, and improved recipient survival. These
      beneficial effects were dose dependent, mimicked by the type V phosphodiesterase
      inhibitor 2-o-propoxyphenyl-8-azapurin-6-one, and inhibited by a cGMP-dependent
      protein kinase antagonist, the R isomer of 8-(4-chlorophenylthio)guanosine 3',5'
      cyclic monophosphorothioate. Augmenting the NO pathway at the level of cGMP
      improves graft function and recipient survival following lung transplantation.

PMID- 7527551
TI  - Similarity of nucleotide interactions of BiP and GTP-binding proteins.
AB  - BiP is a member of the Hsp70 heat shock protein family found in the lumen of the
      endoplasmic reticulum, that binds to a variety of proteins destined to be
      secreted. Substance P (SP) has been used as a model peptide to study the
      interaction of BiP with protein substrates. SP stimulates BiP ATPase activity and
      forms a stable complex with BiP that is dissociated in the presence of levels of
      ATP > 50 microM. At lower concentrations of ATP, the SP remains bound to BiP, and
      the results are consistent with the view that a BiP-ATP complex is initially
      formed that reacts with SP to form a ternary complex, SP-BiP-ATP. Hydrolysis of
      ATP in this complex yields a SP-BiP-ADP complex. An exchange of ATP with ADP
      bound to BiP has also been demonstrated, and the results suggest that the
      interactions of BiP with ATP resemble those seen with GTP-binding proteins and
      GTP.

PMID- 7527552
TI  - CD40-deficient mice generated by recombination-activating gene-2-deficient
      blastocyst complementation.
AB  - To study the role of B-cell antigen CD40 in immune responses, mouse embryonic
      stem (ES) cells in which both copies of the gene encoding CD40 had been disrupted
      by homologous recombination were injected in RAG-2 (recombination-activating gene
      2)-deficient blastocysts to generate chimeras in which all mature lymphocytes are
      derived from the CD40-deficient ES cells. T- and B-cell number and phenotype were
      normal in the CD40-/- chimeras. However, B cells failed to proliferate and
      undergo isotype switching in vitro in response to soluble CD40 ligand (sCD40L)
      with interleukin 4 (IL-4) but responded normally to lipopolysaccharide (LPS) with
      IL-4. CD40-/- chimeras completely failed to mount an antigen-specific antibody
      response or to develop germinal centers following immunization with the T cell
      dependent (TD) antigen keyhole limpet hemocyanin. In contrast, CD40-/- mutant
      mice responded normally to the T cell-independent (TI) antigens, 2,4,6
      trinitrophenyl (TNP)-LPS and TNP-Ficoll. The most noticeable alteration in the
      serum immunoglobulin levels of young (6-8 weeks old) CD40-/- animals was absence
      of IgE and severe decrease of IgG1 and IgG2a. These results confirm the essential
      role of CD40- CD40L interactions in the antibody response to TD antigens and in
      isotype switching.

PMID- 7527548
TI  - Asymmetrical blockade of the Ca2+ release channel (ryanodine receptor) by 12-kDa
      FK506 binding protein.
AB  - A soluble 12-kDa FK506 binding protein (FKBP12), the cellular receptor of the
      immunosuppressive drug FK506, is tightly associated with the Ca2+ release channel
      of rabbit skeletal muscle sarcoplasmic reticulum [Jayaraman, T., Brillantes, A.
      M., Timerman, A. P., Fleischer, S., Erdjument-Bromage, H., Tempst, P. & Marks, A.
      (1992) J. Biol. Chem. 267, 9474-9477]. We have assessed the role of excess free
      FKBP12 in the function of single Ca2+ release channels incorporated into planar
      lipid bilayers. The addition of human recombinant FKBP12 (hFKBP12) to the
      cytoplasmic face of the Ca2+ release channel blocked the flow of cytoplasmic to
      luminal current (outward current) in a concentration-dependent manner but had no
      significant effect on the flow of luminal to cytoplasmic current (inward
      current). The luminal to cytoplasmic flow of current was modulated by Ca2+, Mg2+,
      ATP, caffeine, and ryanodine in the presence and absence of FKBP12. An
      immunosuppressive drug, L-683,590, an analog of FK506, did not block or reverse
      the asymmetrical hFKBP12 blockade of single Ca2+ release channels in planar lipid
      bilayers. FKBP12 may play a role in regulation of the flow of ions into the lumen
      of the sarcoplasmic reticulum through the Ca2+ release channel.

PMID- 7527554
TI  - Cross-talk between cyclooxygenase and nitric oxide pathways: prostaglandin E2
      negatively modulates induction of nitric oxide synthase by interleukin 1.
AB  - The inflammatory cytokine interleukin 1 beta (IL-1 beta) induces both
      cyclooxygenase (COX) and nitric oxide synthase (NOS) with increases in the
      release of prostaglandin (PG) and nitric oxide (NO) by mesangial cells. Recently,
      activation of the COX enzyme by NO has been described. However, the effects of
      COX products (PGs) on the NO pathway have not been fully clarified. Thus we
      determined the effect of COX inhibition and exogenous PGs on NO production and
      NOS induction in rat mesangial cells. A COX inhibitor, indomethacin, enhanced IL
      1 beta-induced steady-state level of the inducible NOS (iNOS) mRNA and nitrite
      production. The effect of indomethacin was dose dependently reversed by the
      replacement of endogenous PGE2 with exogenous PGE2, which is the predominant
      product of the COX pathway in rat mesangial cells. In contrast to PGE2, a stable
      analog of PGI2, carba prostacyclin, enhanced IL-1 beta-induced iNOS mRNA levels
      and nitrite production. Forskolin, an activator of the adenylate cyclase,
      mimicked the effect of carba prostacyclin but not PGE2. These data suggest that
      (i) endogenous PGE2 downregulates iNOS induction, (ii) this inhibitory effect of
      PGE2 on iNOS induction is not mediated by activation of adenylate cyclase, and
      (iii) exogenous PGI2 stimulates COX induction possibly by activation of adenylate
      cyclase.

PMID- 7527557
TI  - Differential expression of homeobox genes in functionally distinct CD34+
      subpopulations of human bone marrow cells.
AB  - Class I homeobox (Hox) genes encode a major group of transcription factors
      controlling embryonic development and have been implicated in the continuing
      process of hematopoietic cell differentiation. They are clustered on four
      chromosomes and, in early development, exhibit spatially restricted expression
      with respect to their 3'-->5' chromosomal position. By using an improved PCR
      based method for amplifying total cDNA derived from limited cell numbers, we now
      describe the expression of class I Hox genes in highly purified CD34+ cell
      subpopulations isolated from normal human bone marrow that represent functionally
      distinct stem and progenitor cell compartments. Our data indicate that at least
      16 different Hox genes, mainly from the A and the B clusters, are expressed in
      one or more of these subpopulations of human hematopoietic cells. Moreover,
      markedly elevated expression of some of the Hox genes found at the 3' end of the
      A and B clusters (e.g., HoxB3) was a unique feature of the subpopulations that
      contained the most primitive functionally defined cells, whereas genes located in
      the 5' region of each cluster (e.g., HoxA10) were found to be expressed at nearly
      equal levels in the CD34+ subpopulations analyzed. In contrast to the findings
      for CD34+ cells, expression of two selected Hox genes, HoxB3 and HoxA10, was
      virtually extinguished in the CD34- fraction of bone marrow cells. These results
      demonstrate the expression of a broad range of Hox genes in primitive
      hematopoietic cells and point to the existence of a regulated program of Hox gene
      expression during their normal development.

PMID- 7527553
TI  - Establishment of an adherent cell feeder layer from human umbilical cord blood
      for support of long-term hematopoietic progenitor cell growth.
AB  - Previous attempts to establish a stromal cell feeder layer from human umbilical
      cord blood (HUCB) have met with very limited success. It has been suggested that
      there is an insufficient number of stromal precursor cells in HUCB to form a
      hematopoietic-supporting feeder layer in primary cultures. The present study
      shows that HUCB does contain a significant accessory cell population that
      routinely develops into a confluent, adherent cell layer under defined primary
      culture conditions. HUCB-derived adherent layers were shown to support long-term
      hematopoietic activity for an average of 4 months. This was achieved by using a
      customized coverslip with a modified surface structure as the cell attachment
      substratum and using a specialized culture feeding regime. We have characterized
      the various cell types (including fibroblasts, macrophages, and endothelial
      cells) and extracellular matrix proteins (including fibronectin, collagen III,
      and laminin) that were present in abundance in the HUCB-derived adherent cell
      layer. In contrast, oil red O-staining fat cells were rarely detected. ELISA and
      bioassays showed that stem cell factor and interleukin 6 were produced by the
      HUCB stromal cell cultures, but interleukin 3 or granulocyte/macrophage colony
      stimulating factor was not detected. Application of this hematopoietic culture
      system to transgenic and gene therapy studies of stem cells is discussed.

PMID- 7527555
TI  - Three-dimensional structure of the platelet integrin recognition segment of the
      fibrinogen gamma chain obtained by carrier protein-driven crystallization.
AB  - We have developed a method for crystallizing small functional protein segments so
      that their three-dimensional structure can be determined by x-ray diffraction
      analysis. This method consists of linking a small protein segment of unknown
      tertiary structure to either the amino or carboxyl terminus of a larger carrier
      protein of known tertiary structure. Crystallization of the small segment is then
      driven by crystallization of the carrier protein. Using this approach, we have
      obtained crystals of the human fibrinogen gamma-chain carboxyl-terminal segment
      linked to the carboxyl terminus of chicken egg white lysozyme. The three
      dimensional structure of the carboxyl-terminal segment of the fibrinogen gamma
      chain was determined by x-ray diffraction analysis at a resolution of 2.4 A. This
      segment encompasses the recognition site for the integrin alpha IIb beta 3
      receptor on activated platelets and for the clumping receptor on pathogenic
      staphylococci and also bears donor and acceptor sites for factor XIIIa-catalyzed
      crosslinking of fibrin. Therefore, the structural information derived from our
      analysis will provide a rational basis for the design of inhibitors of these
      important functions of fibrinogen. Moreover, carrier protein-driven
      crystallization will facilitate the determination of the three-dimensional
      structure of functional segments of other proteins that are, like fibrinogen,
      difficult to crystallize in toto.

PMID- 7527556
TI  - Human immunodeficiency virus type 1 (HIV-1) inhibition, DNA-binding, RNA-binding,
      and ribosome inactivation activities in the N-terminal segments of the plant anti
      HIV protein GAP31.
AB  - GAP31 (gelonium anti-HIV protein of 31 kDa) is an anti-HIV protein which we have
      identified and purified from a medicinal plant, Gelonium multiflorum. It is
      capable of inhibiting HIV-1 infection and replication. GAP31 also exhibits DNA
      topoisomerase inhibitor activity and RNA N-glycosidase activity. The ability of
      GAP31 to interrupt both DNA and RNA functions may be related to its multiple
      antiviral actions. To define the roles of these activities in the anti-HIV action
      of GAP31, a series of peptides corresponding to the N-terminal segment of GAP31
      were synthesized and assayed for the aforementioned activities of the parent
      molecule. A 33-aa segment (KGATYITYVNFLNELRVKTKPEGNSHGIPSLRK) designated as K10
      K42 is the shortest peptide necessary and sufficient for HIV-1 inhibition, DNA
      and RNA binding, and ribosome inactivation. The peptides were 2-5 orders of
      magnitude less active than GAP31. Truncation of 19 aa from the C terminus of K10
      K42 resulted in the loss of all of these activities. On the other hand, deletion
      of N-terminal residues to give E23-K42 did not alter ribosome-inactivation
      activity but eliminated the other activities. These findings permit
      identification of a 7-aa sequence, KGATYIT, at the N terminus of K10-K42 that is
      critical for DNA binding and RNA binding, whereas a 9-aa sequence, SHGIPSLRK, at
      the C terminus is important to ribosome inactivation. Both regions contribute to
      anti-HIV activity. Histidine at position 35 is critical for all of these
      activities. The disparity of sequence requirements for inhibition of HIV
      infection and replication and for ribosome-inactivation activity suggests that
      the anti-HIV activity of most ribosome-inactivating proteins may not be the
      result of N-glycosidase activity alone. Mapping the minimal domain of GAP31
      offers insights into the rational design of molecular mimetics of anti-HIV drugs.

PMID- 7527558
TI  - Amino-terminal basic residues of Src mediate membrane binding through
      electrostatic interaction with acidic phospholipids.
AB  - Membrane targeting of pp60src (Src) is mediated by its myristoylated amino
      terminus. We demonstrate that, in addition to myristate, six basic residues in
      the amino terminus are essential for high-affinity binding to the lipid bilayer
      via electrostatic interaction with acidic phospholipids. Specifically, c-Src was
      shown to bind 2500-fold more strongly to vesicles composed of the physiological
      ratio of 2:1 phosphatidylcholine (PC)/phosphatidylserine (PS) than to neutral PC
      bilayer vesicles. The apparent Kd for binding of c-Src to the PC/PS bilayer was 6
      x 10(-7) M. This interaction is sufficiently strong to account for c-Src membrane
      targeting. Mutants of c-Src in which the amino-terminal basic residues were
      replaced by neutral asparagine residues exhibited binding isotherms approaching
      that of wild-type binding to neutral bilayers (apparent Kd of 2 x 10(-3) M). The
      transforming v-Src and activated c-Src (Y527F) proteins also bound more strongly
      to PC/PS bilayers (apparent Kd of approximately 1 x 10(-5) M) than to neutral PC
      bilayers. In vivo experiments with Src mutants confirmed the role of positive
      charge in mediating membrane binding and cellular transformation.

PMID- 7527559
TI  - Complex correlation between excitatory amino acid-induced increase in the
      intracellular Ca2+ concentration and subsequent loss of neuronal function in
      individual neocortical neurons in culture.
AB  - Primary cultures of cerebral cortical neurons and single-cell imaging of
      intracellular free Ca2+ concentration ([Ca2+]i) with the ratiometric dye fura-2
      were used to assess excitatory amino acid (EAA)-induced neurotoxicity; the loss
      of neuronal function as defined by the ability of the cells to respond to K(+)
      induced depolarization by a transient increase in Ca2+ influx was measured. The
      responsiveness of individual neurons was measured quantitatively as the [Ca2+]i
      values of the second KCl (2.KCl) stimulation divided by those of the first KCl
      (1.KCl) stimulation, giving the value of the ratio (2.KCl/1.KCl). Exposure to
      EAAs led to an increase in [Ca2+]i, but no simple correlation between the
      increase in [Ca2+]i and neuronal responsiveness could be demonstrated. Rather,
      below a threshold level of [Ca2+]i (ca. 1 microM), the neuronal responsiveness
      was largely independent of the glutamate receptor-agonist-induced increase in
      [Ca2+]i. However, when [Ca2+]i increased above this threshold level, the neurons
      almost invariably lost the ability to respond to a K(+)-induced depolarization,
      particularly after exposure to glutamate. Therefore, the cortical neurons were
      found to be exceptionally vulnerable to the glutamate-induced loss of function
      when compared with the effect induced by the glutamate receptor subtype-specific
      agonists, N-methyl-D-aspartate, quisqualate, and 2-amino-3-(3-hydroxy-5
      methylisoxazol-4-yl) propionate. The findings suggest that the loss of neuronal
      membrane polarization precedes plasma membrane disruption and is a sensitive
      marker of EAA-induced neurodegeneration observed at the single-cell level.

PMID- 7527562
TI  - Differential replication of plasmids during stringent and relaxed response of
      Escherichia coli.
AB  - Stringent control of DNA replication has been demonstrated for a few replicons
      like oriC, pBR322, and plasmids derived from coliphage lambda. In this study we
      investigated the replication of other plasmids harboring a well defined origin
      (orip15A, oripSC101, and oriRK2 = oriV) in amino-acid-starved stringent and
      relaxed strains of Escherichia coli. We found differential replication of
      plasmids during stringent and relaxed response. Inhibition of DNA synthesis or
      amplification of plasmid DNA in amino acid-starved relA+ and relA- cells depends
      on the kind of replicon and, surprisingly, on the nature of deprived amino acid.
      We conclude that there are no general rules for stringent control of DNA
      replication and each replicon must be considered separately. There are, however,
      possible explanations for the differences shown between replicons in their
      response to stringent and relaxed conditions.

PMID- 7527561
TI  - Merocyanine dyes: effect of structural modifications on photophysical properties
      and biological activity.
AB  - Merocyanine derivatives were prepared by structural alterations at the barbituric
      acid or chalcogenazole moieties. The photophysical properties of the dyes were
      markedly influenced by the presence of selenium rather than sulfur as a
      substituent at position 2 of the barbiturate. In methanol, quantum yields of both
      triplet state (phi T) and singlet oxygen sensitization (phi delta) were increased
      by over an order of magnitude, with a concomitant decrease in fluorescence, when
      selenium was present in the molecule. Photoisomerization, one of the dominant
      deactivation pathways in the sulfur- or oxygen-containing analogues, was
      completely absent in the selenium-containing derivatives. Efficient triplet state
      formation was observed for selenium-containing derivatives incorporated into
      L1210 cells by diffuse reflectance laser flash photolysis. Cytotoxicity studies,
      carried out using clonogenic assays on L1210 leukemia cells, showed a good
      correlation with phi T and phi delta, measured in solution. Experimental evidence
      provided by this paper supports a triplet state-, and probably singlet oxygen-,
      mediated phototoxic mechanism. Photoisomerization or singlet state mechanisms can
      be discounted.

PMID- 7527560
TI  - cDNA cloning of the Sm proteins D2 and D3 from human small nuclear
      ribonucleoproteins: evidence for a direct D1-D2 interaction.
AB  - The major small nuclear ribonucleoproteins (snRNPs) U1, U2, U4/U6, and U5 share a
      set of common proteins denoted B/B', D1, D2, D3, E, F, and G which play an
      important part in the biogenesis of the snRNPs. In addition, there is a link
      between the common proteins and autoimmunity; the three D proteins, together with
      B/B', are the major autoantigens for the so-called anti-Sm antibodies often
      produced by patients suffering from systemic lupus erythematosus. Here we
      describe the characterization of the human proteins D2 and D3 by cDNA cloning and
      immunological methods. D2 and D3 are encoded by distinct genes and are 118 and
      126 amino acids in length, respectively. Both proteins prepared by in vitro
      translation exhibit Sm epitopes and can be precipitated by anti-Sm
      autoantibodies. They react differently with various patient sera, in a manner
      consistent with the reaction pattern on immunoblots of the D proteins isolated
      from HeLa cells. D1 and D2 synthesized in vitro form specific complexes, a result
      that is significant for the assembly pathway of the various core proteins into an
      snRNP's core ribonucleoprotein structure. The D3 protein is homologous to the
      human D1 protein, showing an overall amino acid sequence identity of 29%,
      including two regions with over 60% identity. D2 has less than 15% sequence
      identity with D1 and D3. A data bank search revealed a striking similarity (with
      more than 40% sequence identity) between human D3 and a Saccharomyces cerevisiae
      gene, previously published as the 5' flanking gene of yeast pep3 [Preston, R.A.,
      Manolson, M., Becherer, K., Weidenhammer, E., Kirkpatrick, D., Wright, R. &
      Jones, E. (1991) Mol. Cell. Biol. 11, 5801-5812], suggesting that this gene
      encodes the yeast homologue of the human D3 protein.

PMID- 7527563
TI  - [Developmental disorders in the fourth edition of the American classification:
      diagnostic and statistical manual of mental disorders (DSM IV -- optional book)].
AB  - In 1991 the American Psychiatric Association proposed a draft version of the IV
      edition of the Diagnostic and Statistical Manual of Mental Disorders--the DSM IV
      Options Book. Authors of this version wanted to increase clarity of the criteria
      sets and to provide compatibility with the Tenth Edition of the International
      Classification of Diseases (ICD - 10). The purpose of this Options Book is to
      propose some changes in wording, diagnostic divisions and to discuss various
      options concerning the placement of sections and disorders within the
      classification. The "Disorders of Infancy, Childhood or Adolescence" section was
      renamed "Disorders Usually First Evident in Infancy, Childhood or Adolescence"
      and moved to the front of the classification and also was expended to 11 groups
      of disorders. Several suggestions have been made about including new diagnostic
      groupings such as: Rett's Disorder, Eating Disorders and Voice Disorder. The
      Options Book introduces a superior category for Attention Deficit Disorders (with
      and without hyperactivity) and for Conduct Disorder/Oppositional Defiant
      Disorder. Several options are proposed regarding The Anxiety Disorders of
      Childhood or Adolescence. There is no evidence for a distinction in this category
      according to the age criterion. One option would be to move these disorders into
      the adult anxiety section (similarly as in the Mood Disorders and Schizophrenia).
      In the new version the title "Specific Developmental Disorders" is omitted. The
      suggestion is to include Phonological Disorder (Articulation Disorders) and
      Elective Mutism into Speech and Language Disorders section.

PMID- 7527567
TI  - [Alpha fetoproteins curve in maternal serum of normal pregnant women with risk
      antecedents].
AB  - Two hundred ninety four samples of A.F.P. in maternal serum, taken in different
      weeks of gestation are evaluated. The group of patients were over 35 years of age
      and/or had congenital defects or chromosomic disease in previous pregnancy;
      although in the current pregnancy, the fetuses were normal. A chilean curve of
      A.F.P. was determined with this data.

PMID- 7527568
TI  - [Transvaginal ultrasonography in 27 confirmed cases of ectopic pregnancy].
AB  - Twenty seven patients having Ectopic Pregnancies were studied prospectively with
      transvaginal sonography. Ten of them were treated surgically, thirteen with
      injection of methotrexate and four with expectant management. Ultrasound images
      were well correlated with clinics, surgical findings and pathology. We believe
      that the ultrasound image known as "tubal ring" is highly suggesting of early
      ectopic pregnancy. Since early detection is associated with conservative surgery,
      expectant management or treatment with methotrexate, and consequently to a better
      reproductive future, we consider that transvaginal sonography is a reliable
      method that must be added to traditional ones, in the ectopic pregnancy
      management.

PMID- 7527569
TI  - [Medical handling of the tubal pregnancy: results].
AB  - We report the outcome of the treatment with intratubal methotrexate (25 mg)
      administered via laparoscopy in 8 patients with ectopic pregnancy who where
      treated according to a preestablished protocol. A successful treatment was
      achieved in 6 patients (75%). Hysterosalpingography was performed in 5 of the
      patients, and in 4 of them we found bilateral tubal patency. Currently 3 patients
      have a normal intrauterine pregnancy.

PMID- 7527564
TI  - Effects of monoamine oxidase A inhibition on plasma biogenic amine metabolites in
      depressed patients.
AB  - The main metabolites of noradrenalin, dopamine, and serotonin-3-methoxy-4
      hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic
      acid (5-HIAA), respectively--were estimated in plasma of 21 depressed patients
      before and after 2 and 4 weeks of treatment with the monoamine oxidase-type A
      (MAO-A) inhibitor moclobemide (mean final daily dose = 8.9 mg/kg body weight).
      The treatment caused significant mean reductions in plasma MHPG and HVA (46% and
      30%, respectively), while plasma 5-HIAA was unchanged. Multiple regression
      analysis revealed associations between reductions in MHPG and changes on the
      anxiety-somatization factor of the Hamilton Rating Scale for Depression (HRSD),
      and between reductions in HVA and changes in the HRSD factors cognitive
      disturbance and retardation.

PMID- 7527565
TI  - Cerebrospinal fluid monoamine metabolites in boys with attention-deficit
      hyperactivity disorder.
AB  - Cerebrospinal fluid (CSF), plasma, and urinary monoamine metabolites were
      determined for 29 boys, aged 6-12, with attention-deficit hyperactivity disorder
      (ADHD). Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid
      (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), the metabolites of serotonin,
      dopamine, and norepinephrine, respectively, correlated significantly with
      behavioral measures of aggression and impulsivity/hyperactivity. However, these
      correlations were in the unexpected direction; for example, CSF 5-HIAA correlated
      positively with the Brown-Goodwin Lifetime History of Aggression Scale. HVA in
      CSF was positively correlated with several measures of hyperactivity. The
      replicability of these findings, as well as possible socioenvironmental effects,
      and the predictive value of CSF monoamines in prepubertal hyperactivity are the
      subjects of ongoing study.

PMID- 7527566
TI  - Interactions between serotonin, thyrotropin-releasing hormone, and substance P in
      the CNS regulation of adrenocortical secretion.
AB  - Double-labeling immunohistochemical studies were performed to discern the
      morphological relationships between corticotropin-releasing factor-immunoreactive
      (CRF-ir) perikarya and afferent innervation in the hypothalamic paraventricular
      nucleus (PVN) of the rat. Attention was focussed on the local innervation by
      serotonin (5-hydroxytryptamine, 5-HT), thyrotropin-releasing hormone (TRH) and
      substance P (SP)-ir nerve terminal fibers. 5-HT-ir and SP-ir fibers were present
      in moderate numbers, in close apposition with CRF-ir perikarya. Sparse TRH-ir
      fibers were observed, but a population of TRH-ir perikarya was found in proximity
      with the CRF-ir cell bodies. TRH-ir perikarya in the PVN were surrounded by both
      5-HT- and SP-ir fibers. Neuroendocrine studies were performed to investigate the
      interactions between 5-HT, TRH and SP in the regulation of hypothalamo-pituitary
      adrenocortical (HPA) secretion. Male rats were prepared bearing cannulae for
      intracerebroventricular (ICV) or intra-PVN administration of drugs. 5-HT, at all
      doses tested (0.1, 40, or 80 nmol, ICV), caused increases in plasma
      corticosterone (CS) concentrations in tail-vein blood collected 20 min after
      injection. ICV injections of TRH caused dose-dependent increases in plasma CS,
      but did not further increase HPA responses when injected together with 5-HT. SP
      alone had little effect, although a significant reduction in plasma CS
      concentrations was observed in several individual experiments. However, SP (0.1
      nmol) significantly attenuated CS responses following high doses of 5-HT (40 and
      80 nmol, ICV), although the response to 0.1 nmol 5-HT was not affected. Combined
      injection of SP with TRH resulted in HPA responses not different from those
      following TRH alone. Similarly, SP did not reduce the HPA response observed with
      TRH and 40 nmol 5-HT in combination. Intra-PVN injections of 5-HT (0.1 or 40
      nmol) and TRH also increased plasma CS concentrations. Intra-PVN injections of SP
      had little effect on plasma CS concentrations although a tendency toward a
      decrease in plasma CS was observed, as with the ICV injections. Combined intra
      PVN injection of 5-HT (0.1 nmol) with TRH (0.1 nmol) did not significantly alter
      the response compared with that observed following TRH alone, although plasma CS
      concentrations were greater than with 0.1 nmol 5-HT. Combined intra-PVN
      injections of SP (0.1 nmol) with 5-HT (0.1 nmol) resulted in a significant
      decrease in plasma CS concentration compared with that following 5-HT alone, but
      SP did not prevent the CS response to a higher dose of 5-HT (40 nmol).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7527570
TI  - GABAergic activity of quisqualamine and homoquisqualamine in hemisected spinal
      cord in vitro preparation.
AB  - alpha-Decarboxylation of excitatory amino acids can produce derivatives with
      depressant actions on the central nervous system. Examples are aspartate-B
      alanine and glutamate-GABA. Quisqualate derivatives by alpha-decarboxylation,
      Quisqualamine (QUAM) and Homoquisqualamine (HOMOQUAM) (with an extra methylene
      group in the molecular chain), were studied in isolated spinal cord in vitro
      preparation. Dose-dependent depolarizations and inhibition of spontaneous ventral
      root potentials (sVRP) were induced by QUAM and HOMOQUAM in unblocked, Mg2+ free,
      hemisected cord. Ventral root evoked potentials by electrical stimulation of
      dorsal root (2ms, 30V, pulse/30 sec) (DR-VRP) remained unchanged. In Tetrodotoxin
      (TTX) medium, HOMOQUAM showed a twofold increment of relative potency respect to
      QUAM depolarizations. Actions evoked by QUAM and HOMOQUAM were not affected by
      the addition of N-Methyl-D-Aspartate (NMDA) receptor blockers Mg2+ and DL-AP5;
      non-NMDA antagonist CNQX and GABA B receptor antagonist 2-hydroxysaclofen. In
      presence of GABA A receptor blockers Bicuculline MeCl or Picrotoxin, the actions
      evoked by QUAM and HOMOQUAM were blocked. The results obtained show that GABA A
      receptor seemed to mediate QUAM and HOMOQUAM activity in spinal cord in vitro
      preparation. The addition of a methylene group in the molecular chain increased
      the potency twice although the kinetic of the drug did not appeared to have
      changed. The development of new compounds with depressant activity in the central
      nervous system may be useful in assessing the physiological and therapeutic
      significance of central GABA receptors, especially if the blockade of spontaneous
      activity is not followed by an alteration of the neuronal integration and
      synaptic transmission reflected in the DR-VRP.

PMID- 7527571
TI  - Effect of ouabain on membrane conductances and volume in A6 cells.
AB  - The present study reports the effect of a reduction in the Na(+)-transport rate
      on cell volume. A decrease in transport rate was achieved by inhibition of the
      basolateral Na+/K+ pump with ouabain. Cultured A6 cell monolayers were short
      circuited and exposed to ouabain at the basolateral surface. In one series of
      experiments, cells were impaled with microelectrodes to measure cell voltage,
      apical fractional resistance and thus derive membrane conductances. Another set,
      A6, served for cell height measurements. Ouabain decreased short-circuit current
      (Isc), which is an index of transepithelial Na+ transport: the reduction in
      transport rate varied from 26 to 79% within 10 min. Equivalent circuit analysis
      revealed a 20% decrease in apical membrane conductance (ga), whereas basolateral
      membrane conductance (gb) increased by 66%. A decrease in cell voltage (12 mV)
      together with drop in ga during ouabain may account for the reduction in Isc. The
      rise in gb is mainly due to a gain in Cl- conductance which increased from 114 to
      613 microS/cm2, compatible with activation of Cl- channels. All of this occurs
      without a detectable change in cell height. We may conclude from these data that
      inhibition of Na+ exit by ouabain is quickly compensated by a decrease in apical
      Na+ entry and an increase in basolateral Cl- conductance. Constant cell volume
      during ouabain implies that the total cell solute is essentially unchanged.

PMID- 7527572
TI  - Proximal Na+, fluid and HCO3- reabsorption in uninephrectomized rats after a
      saline load.
AB  - We studied the effect of a saline load on proximal tubular Na+, fluid and HCO3-
      handling of control and uninephrectomized (UNx) rats. Glomerular filtration rate
      (GFR) was measured by inulin clearance, Na+ reabsorption in the proximal tubule
      by lithium clearance (CLi+), proximal tubule fluid reabsorption (Jv) by
      microperfusion with 14C inulin and proximal tubule HCO3- reabsorption (JHCO3-) by
      estimating pH of perfusate and collected fluid in vitro under CO2 equilibrated
      oil by means of Sb microelectrodes. No significant differences were found between
      control and UNx animals in baseline values of urine flow, GFR, fractional water
      and sodium excretion and blood and urine pH and pCO2, showing that renal function
      was compensated 4 weeks after UNx. On the other hand, UNx rats showed a
      significant increase in proximal tubule Jv and JHCO3-. After extracellular fluid
      volume expansion (EFVE) by infusion of HCO3- Ringer solution (0.1 ml/min) during
      90-120 min, in both groups of animals hematocrit decreased by 15%, GFR remained
      unchanged and fractional Na+ and water excretion increased significantly.
      However, after EFVE Jv and JHCO3- decreased significantly in control rats but
      were not modified in UNx animals. Fractional proximal Na+ reabsorption as
      measured by CLi+ decreased in control rats after EFVE and was not altered in UNx
      rats. After EFVE the fall in fractional distal Na+ reabsorption was significantly
      higher in control than in UNx rats. The present results provide evidence that
      after a saline load the impaired natriuretic response in UNx rats could be
      attributed to an alteration in proximal and distal tubular Na+ and HCO3-
      handling.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527574
TI  - Glucose metabolism in dog inner medullary collecting ducts.
AB  - The adenosine triphosphate (ATP) generating pathways of dog inner medullary
      collecting ducts (IMCD) were examined in vitro using suspensions of dog IMCD
      tubules incubated under aerobic and anaerobic conditions. Glucose is always the
      preferred substrate for this tissue, even if lactate can be oxidized under
      aerobic conditions. The metabolism of glucose proceeds largely towards lactate
      accumulation in the presence or absence of oxygen. Glycogen is also consumed and
      more markedly so during anoxia. The pentose shunt represents a minor pathway for
      glucose metabolism in this tissue. Under aerobic conditions, the net oxidation of
      glucose to CO2 contributes significantly to the cell energetics, mitochondrial
      and cytoplasmic mechanisms sharing equally the ATP synthesis. In the absence of
      oxygen, only the cytoplasmic routes of ATP synthesis are used, but the apparent
      ATP turnover is markedly reduced. A marked inhibition of the activity of the Na-K
      ATPase during anoxia explains this observation. The utilization of glucose for
      osmolyte synthesis is a minor process and appears to be suppressed under
      anaerobic conditions. It is concluded that the ATP turnover is low in dog IMCD
      cells as compared with that of other nephron segments and is largely dependent
      upon glucose availability under aerobic or anaerobic conditions.

PMID- 7527573
TI  - In vivo hydrogen peroxide production in rat remnant kidney.
AB  - In the rat remnant kidney hydrogen peroxide (H2O2) production is increased when
      compared to the normal kidney. The activities of the peroxisomal H2O2-producing
      oxidases, D-amino acid oxidase and acyl-coenzyme A oxidase, and of the
      extraperoxisomal superoxide dismutase are decreased in renal homogenate. The
      peroxisomal L-alpha-hydroxyacid oxidase and L-lactate oxidase as well as the
      peroxisomal H2O2 scavenger catalase preserve their activity. The activity of the
      cytosolic scavenging system, glutathione peroxidase, is decreased by 40%. A
      starvation period of 48 h does not produce a measurable increase in H2O2
      production in the normal nor in the remnant kidney. On visual inspection,
      peroxisomal morphology and distribution in the renal tubules are similar in the
      normal and remnant kidney tissue.

PMID- 7527575
TI  - Human fibroblasts in culture exhibit a low sensitivity against cyclosporin A
      treatment.
AB  - The nephrotoxicity of cyclosporin A (CSA) after chronic treatment is well known
      and includes in later stages tubular atrophy associated with interstitial
      fibrosis. In order to examine whether interstitial fibrosis due to CSA treatment
      in vivo is related to a hyperproliferative activity of fibroblasts, the effects
      of CSA on the growth characteristics of cultured human skin fibroblasts (HUSF)
      were investigated at CSA concentrations ranging from 10 ng/ml to 50
      micrograms/ml. We found that CSA at concentrations higher than 7.5 micrograms/ml
      inhibited cell proliferation (p < 0.05 at concentrations above 5 micrograms/ml; n
      = 3) and cloning efficiency (p < 0.05 at concentrations above 5 micrograms/ml; n
      = 3) in a dose-dependent manner and caused a promotion of cell attachment at
      concentrations above 10 micrograms/ml (p < 0.05; n = 4), but did not influence
      cell spreading. At lower concentrations CSA-treated HUSF did not differ in their
      growth characteristics from the corresponding controls. A 50% inhibition of
      proliferation was calculated by extrapolation for a CSA concentration of 70
      micrograms/ml for HUSF. The inhibition of HUSF proliferation was reversible even
      at the highest CSA concentration of 50 micrograms/ml. Under the same experimental
      conditions, a 50% inhibition of proliferation was observed for Madin-Darby canine
      kidney (MDCK) cells to be 5.5 micrograms/ml, e.g. at a 15-fold lower CSA
      concentration. Moreover, CSA caused a dose-dependent and reversible cell
      elongation of HUSF and a significant increase in the average cell diameter from
      19.2 +/- 0.3 microns (control; mean +/- SEM, n = 4) to 22.2 +/- 0.2 microns for
      50 micrograms/ml CSA (mean +/- SEM, n = 4) and in median cell volume from 4,210
      +/- 160 fl (control; mean +/- SEM, n = 4) to 7,020 +/- 190 fl for 50
      micrograms/ml CSA (mean +/- SEM; n = 4). These alterations described above were
      not correlated with a cytotoxic effect as checked by a fluorescent staining for
      cell vitality. Alterations in the organization of cytoskeletal components such as
      stress fibers, intermediate-sized filaments and microtubules directly due to CSA
      treatment were not observed. In contrast, the amount of fibronectin present on
      the cell surface was considerably increased by CSA. Although HUSF in culture do
      not respond to CSA treatment by an increased proliferative activity, they are
      much less affected by CSA than other cell types (i.e MDCK cells).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7527577
TI  - The role of CD40L (gp39)/CD40 in T/B cell interaction and primary
      immunodeficiency.

PMID- 7527579
TI  - Contact-mediated signals and cytokines involved in B-cell activation and isotype
      switching in pre-B and mature B cells.

PMID- 7527578
TI  - The understanding of contact-dependent T-cell helper function in molecular,
      cellular and physiological detail.

PMID- 7527580
TI  - CD40-mediated regulation of human B-cell responses.

PMID- 7527581
TI  - Functional CD40 on B lymphocytes and dendritic cells.

PMID- 7527576
TI  - The role of CD40 and its ligand (gp39) in peripheral and central tolerance and
      its contribution to autoimmune disease.

PMID- 7527584
TI  - [Fetoplacental antigens in pregnancies with fetal chromosomal aberrations].
AB  - Performing prenatal diagnosis of congenital developmental abnormalities, the
      authors have studied two biochemical parameters in maternal serum: alpha-1
      fetoprotein (MS AFP) and trophoblast-specific beta-1-glycoprotein (MS SP1). MS
      AFP and MS-SP1 examinations were performed between the 15th and 20th week of
      pregnancy as a screening of all pregnant women in Benesov district (n = 3150),
      all risk pregnancy patients of the faculty hospitals of the First Medical
      Faculty, and patients of the Department of Medical Genetics (First Medical
      Faculty). The group studied also includes five retrospectively traced patients in
      the third trimester of pregnancy who had delivered fetuses with chromosomal
      aberations. Sevatest ELISA AFP Micro I kit (USOL) was used to assess MS AFP. The
      results were computerized using KIM programme (USOL). MS SP1 was assessed by
      simple radial immunodiffusion with the use of Q antiserum SwAHu/SP1 and standard
      serum (USOL). During prenatal screening of women in the second trimester of
      pregnancy 6 morbus Down fetuses have been detected. In three of these patients
      the levels of MS AFP were lower or equal to 0.5 multiples of the median (MOM), in
      three women MS SP1 levels were higher than 1.9 MOM MS SP1, both pathological
      parameters having been found in two patients. In pregnancies with Edwards
      syndrome fetuses MS AFP levels were physiological or slightly elevated. MS SP1
      levels being 1.6 and 1.9 MOM respectively. In patients in the third trimester of
      pregnancy the MS SP1 values were 1.1 to 2.1 MOM. In the patient with Edwards
      syndrome fetus MS SP1 levels were repeatedly found to be physiological.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7527583
TI  - [Disorders of fetoplacental function in pregnant women with diabetes].
AB  - The paper presents the first results obtained as a part of a screening programme
      of detection of congenital developmental defects of the fetus. Pregnancies with
      diabetes are one of the risk groups in this respect. We have divided our patients
      (n = 58) into two groups. In the first there were 28 diabetics in the 15th-16th
      week of pregnancy. They were examined for alpha-1-fetoprotein (MS AFP) and
      trophoblast-specific beta-1-glycoprotein (MS SP1): in chosen cases chorionic
      gonadotropine (MS HCG) was assessed at the same time. The second group were 35
      insulin-dependent pregnant diabetics followed-up in Regional Ambulance of Central
      Bohemia and hospitalized at the First Clinic of Obstetrics and Gynaecology of the
      First Medical Faculty, whose MS SP1 levels were being assessed (usually in one
      week intervals) during the second and third trimester of pregnancy. 21 patients
      were simultaneously examined for glycated serum proteins. Our study confirmed MS
      AFP levels of diabetics in the 15th-16th week of pregnancy to be range of low
      limit of normal values (0.5-1.0 MOM). MS HCG levels in sera of diabetics ranged
      from 5,000 to 60,000 IU/ml in the 15th-16th week. Comparing glycated serum
      proteins of women with physiological pregnancies with those of healthy non
      pregnant controls we had found no differences. In diabetics the values found in
      the second and third trimester of pregnancy were increased.

PMID- 7527582
TI  - Characterization of the mouse monoclonal antibody TJ4C4 directed at human p68
      kinase.
AB  - This report describes the production and characterization of a mouse monoclonal
      antibody (mAb) TJ4C4, which is directed against the interferon-induced double
      stranded RNA-activated protein kinase p68 (PKR). The mAb TJ4C4 was produced
      against p68 which was isolated using a partially purified p68 preparation from
      human cells. The specificity of this mAb is demonstrated in competitive
      inhibition assays using recombinantly produced p68 protein and by
      immunoprecipitation. This mAb is of particular value in that it detects an
      epitope on p68 which is not destroyed in routinely prepared, formalin-fixed
      paraffin-embedded tissues, or in a variety of other commonly used clinical
      fixatives. The inhibition of mAb TJ4C4 by recombinantly produced p68, on human
      tissues sections, validates the specificity of this mAb in histological studies.
      Therefore, mAb TJ4C4 serves as a specific probe to study p68 expression in
      clinically derived tissue specimens.

PMID- 7527585
TI  - Assessment of alpha-fetoprotein in chronic HBsAg carriers and in HBsAg negative
      cirrhosis of the liver.
AB  - Alpha-fetoprotein (AFP) was assessed in 159 subjects with chronic liver disease,
      incl. 125 chronic HBsAg carriers (42 suffered from cirrhosis of the liver) and in
      34 HbsAg negative cirrhotic patients. In the group of 83 patients with chronic
      hepatitis B a slightly elevated AFP value was recorded in 7.2%, however, during
      the check-up examination it was already normal. During a one-year follow up
      hepatocellular carcinoma (HCC) was revealed in 4 of 42 HBsAg positive cirrhoses
      (9.5%) and in 2 of 34 (5.9%) HBsAg negative cirrhoses, the difference was not,
      however, significant. Five patients with HCC had markedly elevated or rising AFP
      value, one patient had abnormal AFP level despite advanced HCC. All cases of HCC
      were diagnosed late, in one patient radical treatment was not successful. We
      conclude that to improve the adverse prognosis of patients with HCC it is
      necessary to follow-up prospectively all patients with cirrhosis of the liver by
      sonography twice a year and examine after the same time intervals serum AFP to
      detect early stages HCC where there is still some chance of successful treatment.

PMID- 7527587
TI  - The stereochemical course of group II intron self-splicing.
AB  - The stereochemical specificities and reaction courses for both self-splicing
      steps of a group II intron have been determined by phosphorothioate substitution
      at the 5' and 3' splice site phosphodiester bonds. Both steps of the splicing
      reaction proceeded with a phosphorothioate in the Sp configuration but were
      blocked by the Rp diastereomer. Both steps also proceeded with inversion of
      stereochemical configuration around phosphorus, consistent with a concerted
      transesterification reaction. These results are identical to those found for
      nuclear precursor mRNA (pre-mRNA) splicing and provide support for the hypothesis
      that group II introns and nuclear pre-mRNA introns share a common evolutionary
      history.

PMID- 7527589
TI  - Resetting the biological clock: mediation of nocturnal circadian shifts by
      glutamate and NO.
AB  - Circadian rhythms of mammals are timed by an endogenous clock with a period of
      about 24 hours located in the suprachiasmatic nucleus (SCN) of the hypothalamus.
      Light synchronizes this clock to the external environment by daily adjustments in
      the phase of the circadian oscillation. The mechanism has been thought to involve
      the release of excitatory amino acids from retinal afferents to the SCN. Brief
      treatment of rat SCN in vitro with glutamate (Glu), N-methyl-D-aspartate (NMDA),
      or nitric oxide (NO) generators produced lightlike phase shifts of circadian
      rhythms. The SCN exhibited calcium-dependent nitric oxide synthase (NOS)
      activity. Antagonists of NMDA or NOS pathways blocked Glu effects in vitro, and
      intracerebroventricular injection of a NOS inhibitor in vivo blocked the light
      induced resetting of behavioral rhythms. Together, these data indicate that Glu
      release, NMDA receptor activation, NOS stimulation, and NO production link light
      activation of the retina to cellular changes within the SCN mediating the phase
      resetting of the biological clock.

PMID- 7527586
TI  - [Alpha-subunit of human chorionic gonadotropin in bronchogenic carcinoma].
AB  - Using radioimmunoassay method the alpha-subunit of human chorionic gonadotropin
      (alpha-HCG) serum levels were measured in 112 bronchogenic carcinoma patients and
      in 48 patients with various non-cancerous lung diseases. The aim of this study
      was to assess the utility of alpha-HCG as a tumor marker for differential
      diagnosis of lung cancer. The incidence of elevated alpha-HCG serum level
      bronchogenic carcinoma group was 4.4%, in non-cancerous diseases group it was
      4.1%, respectively. The difference between these two groups wasn't statistically
      significant. The elevation of the alpha-HCG was unrelated to the histologic type
      of lung cancer. The finding suggest that alpha-HCG serum level can't help in
      discriminating between patients with bronchogenic carcinoma and those with non
      cancerous lung diseases.

PMID- 7527588
TI  - Correction of lethal intestinal defect in a mouse model of cystic fibrosis by
      human CFTR.
AB  - Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic
      fibrosis transmembrane conductance regulator (CFTR). A potential animal model of
      CF, the CFTR-/- mouse, has had limited utility because most mice die from
      intestinal obstruction during the first month of life. Human CFTR (hCFTR) was
      expressed in CFTR-/- mice under the control of the rat intestinal fatty acid
      binding protein gene promoter. The mice survived and showed functional correction
      of ileal goblet cell and crypt cell hyperplasia and cyclic adenosine
      monophosphate-stimulated chloride secretion. These results support the concept
      that transfer of the hCFTR gene may be a useful strategy for correcting
      physiologic defects in patients with CF.

PMID- 7527591
TI  - Overview of platinum chemotherapy in head and neck cancer.
AB  - Platinum-based chemotherapy has been used to treat head and neck cancer for
      approximately 15 years. For patients with recurrent disease, cisplatin/5
      fluorouracil (5-FU) and carboplatin/5-FU combinations have proved superior to
      single agents in producing higher overall response rates. However, survival rates
      are not substantially affected, indicating a need to identify alternative new
      agents with activity. Newly diagnosed patients with advanced stages III and IV
      disease generally have a poor prognosis. The most common site of failure and
      cause of death is locoregional recurrence. To improve survival and alter patterns
      of failure in this population, platinum-based chemotherapy regimens have been
      combined with surgery or radiotherapy as initial curative treatment. Cisplatin/5
      FU chemotherapy in this setting is effective in significantly reducing the
      incidence of distant metastases as shown in several randomized trials. The sole
      indication for induction chemotherapy in patients with advanced laryngeal cancer
      is as an alternative to laryngectomy. The Department of Veterans Affairs
      Laryngeal Cancer Study Group trial demonstrated no significant differences in
      survival in patients who received induction cisplatin/5-FU and radiotherapy or
      total laryngectomy and postoperative radiotherapy. An alternative approach
      utilizing cisplatin or carboplatin alone or combined with 5-FU, administered
      simultaneously with radiotherapy, is under investigation. Pilot data suggest that
      this approach may be more effective in improving locoregional control and hence
      survival. Three intergroup prospective, randomized trials currently are comparing
      sequential chemoradiotherapy, simultaneous chemoradiotherapy, and standard
      radiotherapy alone in advanced nasopharyngeal cancer, advanced resectable
      laryngeal cancer, and unresectable cancers from other sites in the head and neck.
      These trials are designed to definitively address questions of treatment modality
      sequence and its impact on pattern of failure and survival.

PMID- 7527590
TI  - Carboplatin and granulocyte colony-stimulating factor as first-line treatment for
      epithelial ovarian cancer: a phase I dose-intensity escalation study.
AB  - A phase I study of frequently administered carboplatin with recombinant human
      granulocyte colony-stimulating factor (filgrastim) has been performed in patients
      with newly diagnosed epithelial ovarian cancer. Recombinant human granulocyte
      colony-stimulating factor was administered at a dose of 5 micrograms/kg/d for
      days 1 through 12 after carboplatin treatment. Carboplatin doses were calculated
      using a pharmacokinetic formula on an area under the curve (AUC) basis. Four
      doses of carboplatin were planned for each patient. The first cohort of patients
      received an AUC of 5 mg/mL x min every 3 weeks. Subsequently four additional
      cohorts received AUCs of 5, 7, 9, and 8 every 2 weeks. Non-hematologic toxicities
      were mild and not significant. The dose-limiting toxicity was thrombocytopenia
      and occurred at an AUC of 9. Most patients could complete treatment at an AUC of
      7. Results for AUC 8 are awaited. Complete and partial responses were seen in
      most patients at all dose levels.

PMID- 7527592
TI  - High-dose ifosfamide/carboplatin/etoposide: maximum tolerable doses, toxicities,
      and hematopoietic recovery after autologous stem cell reinfusion.
AB  - We treated 115 patients in a phase I/II dose-escalation study of
      ifosfamide/carboplatin/etoposide (ICE) followed by autologous stem cell rescue.
      Patients treated had a variety of diagnoses, including breast cancer (high-risk
      stage II disease with eight or more positive nodes, stage III disease, and
      responsive metastatic disease), non-Hodgkin's lymphoma, Hodgkin's disease, acute
      leukemia in first remission, and various solid tumors that were responsive to
      induction therapy. Patients received autologous bone marrow stem cells or
      peripheral blood stem cells primed by one of several methods. The maximum
      tolerated dose of ICE was determined to be ifosfamide 20,100 mg/m2, carboplatin
      1,800 mg/m2, and etoposide 3,000 mg/m2 when administered as a 6-day regimen. The
      dose-limiting toxicities included acute renal failure, severe central nervous
      system toxicity, and "leaky capillary syndrome" with hypoalbuminemia, profound
      fluid overload, and pulmonary insufficiency. Analysis of hematologic recovery
      based on stem cell source and influence of hematopoietic growth factor
      administration was undertaken. Hematopoietic growth factor use significantly
      reduced neutrophil engraftment time for patients receiving bone marrow stem
      cells, with evidence of earlier recovery times for patients receiving granulocyte
      colony-stimulating factor compared with granulocyte-macrophage colony-stimulating
      factor. Neutrophil recovery times varied based on the source of stem cells used,
      with the earliest engraftment times seen for patients receiving peripheral blood
      stem cells primed with cyclophosphamide and granulocyte colony-stimulating
      factor. Platelet recovery times were not statistically different for any of the
      subsets. In conclusion, the maximum tolerated dose of ICE has been defined, and
      the source of stem cells and the use of hematopoietic growth factors influence
      hematopoietic recovery.

PMID- 7527593
TI  - Octreotide stimulates insulin-like growth factor binding protein-1: a novel
      mechanism of drug action on acromegaly.

PMID- 7527595
TI  - Pharmacologic management of cancer pain.
AB  - The ideal goal of cancer pain management is the combination of comfort and
      function. For the vast majority of cancer pain patients, this balance can be
      achieved with individually titrated opioid analgesics and specifically prescribed
      coanalgesics. Integration of pain blocking procedures and cognitive behavioral
      therapies can further enhance the quality of life of selected patients.
      Comprehensive cancer pain management should be offered in concert with anticancer
      therapy and shares many of its constructs: prevention, early detection, specific
      therapy, combination chemotherapy, dose intensity, combined modalities, and
      psychosocial support. Unlike the control of cancer, the tools to effectively
      control cancer pain are readily available. Their use takes time, skill, and
      commitment and should be the very least that is provided to all cancer patients
      and their families.

PMID- 7527594
TI  - Supportive oncology: forward.

PMID- 7527596
TI  - Supporting a cancer patient's decision to limit therapy.

PMID- 7527597
TI  - Hospice: what to do when anti-cancer therapy is no longer appropriate, effective,
      or desired.

PMID- 7527598
TI  - The promise of biochemical modulation in combined modality therapy.
AB  - This paper reviews evidence that interferon (IFN) potentiates the cytotoxicity of
      radiotherapy or chemotherapy. The results of preclinical models suggest that the
      radiation-enhancing effect may be due in part to cell-cycle synchronization.
      Clinical studies of small numbers of patients indicate that IFN may enhance the
      effect of radiotherapy in localized tumors, such as non-small cell lung cancer
      and head and neck cancer. Interferon augmented the cytotoxicity of cisplatin in a
      murine model, but two clinical studies of patients with non-small cell lung
      cancer had mixed results. Interferon clearly enhances the activity of 5
      fluorouracil (5-FU) in a variety of laboratory models. Three studies are under
      way to evaluate the combined effects of IFN, cisplatin, and 5-FU in patients with
      head and neck cancer. Investigators at the University of Chicago are obtaining
      promising results with IFN and chemotherapy in patients with previously untreated
      stage IV head and neck cancer. The regimen consists of three cycles of induction
      cisplatin, 5-FU, high-dose leucovorin, and IFN followed by surgery and/or seven
      cycles of concomitant chemoradiotherapy. Although toxicity was formidable, 51% of
      65 evaluable patients achieved complete responses to the chemotherapy. Another
      combination that holds promise is IFN and 13-cis-retinoic acid. This combination
      has shown activity in selected solid tumors. The results of available studies
      indicate that biochemical modulation is feasible and promising. Randomized
      clinical trials are needed to confirm the role of IFN as a biochemical modulator.

PMID- 7527599
TI  - Survival following surgical treatment of gastric cancer. A challenge for the
      community endoscopist.
AB  - The management of 124 patient diagnosed with adenocarcinoma of the stomach from
      1971 to 1990 was reviewed. Early gastric cancer increased from 0% to 9% of the
      cases between the first and last quarter of the study. Proximal gastric cancer
      similarly increased from 8% in the first decade to 29% of all cases diagnosed
      during the second decade of the study. Follow-up information was available for
      all patients. Nineteen patients (15%) had no operation and two survived more than
      2 years. Twelve patients had a surgical biopsy only and four had a palliative
      bypass; none survived 2 years. Eighty-six patients (69%) had a surgical resection
      with a 30-day operative mortality of 8% and a 5-year survival of 17%. Prognosis
      was significantly better for patients with T-1 and T-2 tumors and for those with
      distal cancers. Patients with early gastric cancer had 67% 5-year survival. These
      data should encourage efforts to improve the diagnosis of early gastric cancer.

PMID- 7527600
TI  - Laser therapy for esophageal cancer. Results and additional endoscopic
      treatments.
AB  - Between 1/1/1988 and 5/31/1991, we treated 96 patients with laser therapy to the
      esophagus. In 61 inoperable patients, laser therapy has been performed initially.
      In 64% of these 61 patients, laser therapy alone gave sufficient relief of
      symptoms until death. However, in 36% of the patients, additional endoscopical
      interventions had to be performed. In 14 patients (23%), a prosthesis became
      necessary; 13 patients (21%) needed a percutaneous endoscopical gastrostomy. We
      conclude that laser therapy has an important role in the treatment of esophageal
      cancer, but in a significant number of patients, it might not be sufficient
      alone.

PMID- 7527601
TI  - Insulin-like growth factor binding protein-1 at mouse neuromuscular synapses.
AB  - The insulin-like growth factor (IGF) signaling system includes the growth factors
      and their cell surface receptors, along with circulating IGF binding proteins
      (IGFBPs) that may alter and modulate the action of these neurotrophic hormones.
      These IGFBPs, along with IGFs and receptors, have been detected in various
      tissues including the brain. In this study, using polyclonal antibody to human
      IGFBP-1 or bovine IGFBP-2, we found that mouse muscle extracts contain similar
      sized proteins that cross-react with these antibodies on Western immunoblots.
      After establishing that these antibodies reacted with the homologous murine
      IGFBPs, we performed immunocytochemistry to demonstrate the localization of IGFBP
      1 at the neuromuscular junction, a model nicotinic, cholinergic synapse, as well
      as within intramuscular nerves. IGFBP-2, a distinct macromolecule, is present on
      the surface of muscle fibers and is not present within synapses or nerves.

PMID- 7527602
TI  - Disruption of mitochondrial calcium homeostasis following chronic doxorubicin
      administration.
AB  - Doxorubicin (Adriamycin) is an anthracycline antibiotic with broad antineoplastic
      activity. However, the clinical success is limited by the incidence of cumulative
      cardiomyopathy. In vitro, doxorubicin elicits a cyclosporine A-sensitive release
      of calcium from cardiac mitochondria. It has been suggested that this leads to
      mitochondrial calcium cycling and depolarization of membrane potential, which may
      account for the inhibition of mitochondrial respiration and cytotoxicity observed
      with the drug. Implication of a similar mechanism in the manifestation of
      clinical doxorubicin toxicity requires evidence for a disruption of mitochondrial
      calcium homeostasis following chronic in vivo administration. Cardiac
      mitochondria isolated from doxorubicin-treated rats (2 mg/kg/week, s.c. x 13
      weeks) had a lower RCR but no change in ADP/O compared to controls and exhibited
      an enhanced cyclosporine A-sensitive release of mitochondrial calcium. Associated
      with this was a calcium-induced depolarization of membrane potential, which was
      inhibited by either cyclosporine A or ruthenium red suggesting the induction of
      mitochondrial calcium cycling following chronic doxorubicin treatment. The
      persistence of these effects on mitochondrial calcium regulation 4-7 days after
      the last drug treatment is consistent with the cumulative cardiotoxicity
      associated with doxorubicin therapy. Cardiac mitochondria isolated from rats
      treated with iminodaunorubicin, a noncardiotoxic analog of doxorubicin, showed no
      differences from control suggesting that this disruption of mitochondrial calcium
      homeostasis in vivo may be an important determinant of the cardiomyopathy
      observed clinically with doxorubicin.

PMID- 7527603
TI  - Protection of rat endothelial cells from primate complement-mediated lysis by
      expression of human CD59 and/or decay-accelerating factor.
AB  - The present study analyzed the ability of human decay-accelerating factor (DAF)
      and CD59 to protect rat endothelial cell (EC) clones from human and primate
      complement-mediated lysis. By flow cytometry and Scatchard analysis, we show that
      human DAF and/or CD59 cDNAs under the transcriptional control of elongation
      factor 1-alpha promoter were expressed at levels similar to or higher than that
      of a human EC line. Human DAF and CD59 were released from the surface of
      transfected rat cells by phosphatidylinositol phospholipase C, demonstrating that
      the two molecules were linked to the cell membrane by means of a glycolipid
      anchor. The functional activity of the two human C regulatory proteins expressed
      on rat EC lines was studied using an in vitro assay of C-dependent cytotoxic in
      which rat EC were incubated with human or nonhuman primate sera as sources of
      xenogeneic natural antibodies and C. We demonstrate that human and monkey
      xenogeneic natural antibodies bind to rat cells and induce lysis by a C-dependent
      mechanism involving mainly the C direct activation pathway. Our data indicate
      that human DAF and CD59, expressed either alone or in combination, abrogated all
      EC cytotoxicity, even in the presence of 50% human serum. This protective
      phenotype was correlated with decreased membrane attack complex (CD59 and/or DAF
      transfectants) and C3 deposition (DAF transfectants) on EC surface. Antibodies
      against the transfected molecules abolished the protection against C-mediated
      lysis.

PMID- 7527605
TI  - The importance of adenosine and a colloid (Dextran 40) in resuscitation of
      ischemically damaged canine pancreas during preservation by the two-layer method.

PMID- 7527606
TI  - G-proteins in alpha 1-adrenoceptor mediated prostatic smooth muscle contraction.
AB  - The role of signal transducing guanine-nucleotide binding proteins (G-proteins)
      in alpha 1-receptor mediated smooth muscle contractions was investigated in human
      hyperplastic prostatic tissue. The selective alpha 1-receptor agonist
      phenylephrine (PE) evoked dose dependent contractions antagonized by the alpha 1
      receptor blockers prazosin (EC50 10 nM) and YM617 (EC50 3 nM). Application of
      nifedipine (1-10,000 nM), a blocker of voltage-dependent L-type Ca(2+)-channels
      (VDCC), inhibited the PE evoked contraction up to 65.4%. Pretreating the tissue
      strips with pertussis toxin (PTX, exotoxin from Bordetella pertussis; 5-25
      micrograms/ml), inactivating a subpopulation of G-proteins, inhibited the PE
      induced contractions up to 73.9%. PTX pretreatment had no effect on contractions
      elicited by 125 mM K+. Application of nifedipine to PTX pretreated tissue led to
      an additional inhibition of 13.7%. Our findings demonstrate the involvement of
      PTX-sensitive G-proteins in the signal transduction pathway of alpha 1-receptor
      induced contractions of prostatic smooth muscle. The remaining contractility of
      PTX pretreated tissue suggests additional participation of PTX insensitive
      mechanisms in alpha 1-receptor mediated prostatic smooth muscle contractions.

PMID- 7527604
TI  - Fine specificity of peptide determinants for indirect T cell recognition of class
      I MHC alloantigens.
AB  - CD4+ T cells from the LEW (RT1l) rat strain are able to recognize a 24-amino acid
      peptide from the alpha-helical region of the alpha 1-domain of the DA (RT1avl)
      RT1.A class I MHC molecule. This response is known to play a role in the effector
      mechanisms of rejection of DA grafts by LEW recipients. In this study, we
      demonstrate that the WAG (RT1u) strain is also able to respond to this peptide,
      but that the PVG (RT1c) strain does not respond. Fine specificity studies using a
      nested set of 15 mers derived from the 24 mer indicate that the LEW strain
      recognizes multiple T cell epitopes spanning the length of the peptide, while the
      WAG strain response is limited to the N-terminal region. With regard to B cell
      immunity, both the LEW and WAG strains give strong antibody responses when
      immunized with the free peptide, while the antibody response in the PVG strain is
      weak. Interestingly, in all 3 strains, the antibodies appear to be directed at
      the N- and C-terminal regions of the peptide, and to be almost entirely dependent
      upon the presence of the N- and C-terminal amino acids. These studies are
      potentially important when considering the specificity of rejection responses,
      and most particularly when considering the specific suppression of rejection
      mediated by indirect T cell allorecognition.

PMID- 7527607
TI  - On the mode of action of intravesical bacillus Calmette-Guerin: in vitro
      characterization of BCG-activated killer cells.
AB  - Previously we had shown that, upon activation with viable bacillus Calmette
      Guerin (BCG), peripheral blood mononuclear cells (PBMNC) could be rendered
      cytotoxic against otherwise insensitive natural killer (NK)-resistant bladder
      cancer cell lines. This phenomenon had been termed the BCG-activated killer (BAK)
      cell phenomenon. By means of depletion and enrichment procedures of mononuclear
      cell subpopulations derived from BCG-activated PBMNC we further characterized the
      cytolytic BAK effector cells functionally in an in vitro cytotoxicity assay
      against the bladder carcinoma cell line BT-A and phenotypically in their pathway
      of activation. Neither macrophages nor CD4+ T-helper/inducer cells exerted
      cytotoxic BAK activity. This cytotoxicity was restricted to the CD8+CD56+
      subpopulation of T-cytotoxic/NK cells. Furthermore, activation of BAK cells via
      interferon gamma (IFN-gamma) was evidenced by the complete inhibition of BAK cell
      generation with an IFN-gamma antibody.

PMID- 7527609
TI  - Predictive value of anti-HCV reactivity and ALT level.

PMID- 7527608
TI  - Perioperative use of somatostatin in pancreatic surgery.
AB  - The prophylactic effect of perioperative use of somatostatin on postoperative
      increase of pancreatic enzymes was investigated in this double blind, randomized
      study. Thirty tree patients undergoing pancreatic surgery because of chronic
      pancreatitis or its complications were divided randomly into two groups. Fifteen
      patients received somatostatin (dose 125 micrograms/hour), 18 placebo-infusion
      pre-, and postoperatively for a total time of 48 hours. The level of serum
      amylase, lipase, gammaGT, calcium, creatinine and blood glucose was determined
      every 12 hours. In the placebo treated group the serum lipase and amylase
      increased significantly (p < 0.001), while the calcium decreased. In the
      somatostatin treated patients only the lipase level increased significantly (p <
      0.01), while the amylase and calcium showed no significant changes compared to
      their initial values. The postoperative increase in serum enzyme levels is
      interpreted as being an indicator of pancreatic injury. These results suggest
      that the perioperative use of somatostatin has beneficial effect for the
      prevention of pancreatic enzymes increases and of pancreatic injuries, associated
      with pancreatic surgery in patients with chronic pancreatitis. The clinical
      experiences suggest that the asymptomatic increase in pancreatic amylase
      following abdominal surgery is the result of various types of injuries of the
      pancreas (1-3). Included in these injuries is the direct mechanical damage of the
      parenchyma and ducts but it can develop secondary, as a result of vascular
      lesion, ischaemia, oedema as well as mechanical injury to the Oddi sphincter of
      the sphincter's drug induced spasm (1, 2). The asymptomatic increase in serum
      amylase and lipase can thus be interpreted as being an indicator of surgical
      pancreatic injury (3).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527610
TI  - Hydatid cyst of the breast diagnosed by fine needle aspiration biopsy. A case
      report.
AB  - A hydatid breast cyst was diagnosed from hooklets obtained by fine needle
      aspiration biopsy. In rare cases, some palpable lesions suggest a hydatid cyst.
      This possibility should always be considered during routine cytologic
      examination.

PMID- 7527612
TI  - [The outlook for medical ethics in the 1990s].
AB  - The evolution of medicine throughout time--in clinical practice, in scientific
      progress and in the development of new technologies of semeiology and
      therapeutics-, created a long list of ethical problems unknown before. If the
      Hippocratic oath remains valid nowadays, as a true monument of rare moral
      elegance, the truth is, that it began to be unable to cover all the new aspects
      created by the evolution of Medicine on one hand, and the transformation of the
      Society, on the other hand. Therefore, the confrontation of the traditional
      principles of Medical ethics with the new realities is mandatory, to analyse a
      long list of well defined questions such as, clinical trials, human
      experimentation, problems related with the creation of life and its ending, organ
      transplants molecular biology, medical genetics, analysis of, human genome and
      its consequences, new biotechnologies, as well as other questions that are
      covered by the broader aspect of bioethics, interlinking in this way several
      areas of knowledge. All the technologies used in clinical practice, radically
      changed the traditional relation between the doctor and the patient, and created
      not only a number of new problems, but also, clear threats to medical secrecy and
      patient privacy. The exponential increase in the number of terminal patients made
      for way some temptations (intensive care, euthanasia) and for the idea of
      developing a correct structure palliative Medicine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7527611
TI  - [Stem cell factor].
AB  - Stem cell factor (CSF), also called c-kit ligand (KL) or mast cell growth factor
      (MGF) is a peptide growth factor/cytokine with broad activities, especially on
      hematopoiesis. Its physiological role is best understood through the naturally
      occurring steel and W mutations in the mouse. This cytokine has recently been
      made available because of molecular cloning and its expression in recombinant
      form SCF is produced by a variety of cells, especially fibroblast, and interacts
      with target cells in each of the hematopoietic lineages to stimulate
      proliferation and differentiation. It has been found that SCF is important for
      the survival, proliferation and differentiation of mast cells and that it
      influences all stages of their development. SCF activity is not restricted to
      hematopoiesis, as it plays an important role in the development of germ cells and
      melanocytes as well. Preclinical studies show that SCF can protect against lethal
      irradiation, elicit multilineage responses in peripheral blood and bone marrow
      cellularity and increase circulating peripheral blood progenitor cells in a dose
      dependent manner. Recombinant human SCF has major clinical potential through its
      synergy with other factors, especially G-CSF, to enhance mobilization of stem
      cells in peripheral blood.

PMID- 7527614
TI  - Directed and random biopsies of the prostate: indications based on combined
      results of transrectal sonography and prostate-specific antigen density
      determinations.
AB  - OBJECTIVE: We studied the usefulness of transrectal sonography, prostate-specific
      antigen levels, and prostate-specific antigen density as indications for directed
      and random biopsies of the prostate in patients with possible prostatic cancer.
      MATERIALS AND METHODS: A total of 141 patients with increased levels of prostate
      specific antigen or abnormal findings on digital rectal examination had
      transrectal sonography of the prostate and determination of prostate-specific
      antigen density. Through sonographic visualization, all patients had biopsies of
      possible cancerous lesions and random biopsies of regions of the prostate that
      appeared normal. Histologic results were correlated with sonographic findings and
      determinations of prostate-specific antigen levels and prostate-specific antigen
      density. RESULTS: Adenocarcinoma was detected in 40 (28%) of the 141 patients.
      Transrectal sonography showed an abnormality that was determined by directed
      biopsy to be a carcinoma in 27 (68%) of the 40 patients. Transrectal sonography
      showed no carcinoma in 13 patients (32%) for whom random biopsy revealed a tumor.
      The sensitivity of sonography was 68%, and the specificity was 49%. The
      combination of sonographic findings suggestive of cancer and increased prostate
      specific antigen density had a sensitivity of 75% and a specificity of 75%; we
      calculated a sensitivity of 72% and a specificity of 56% for the combination of
      sonographic findings suggestive of tumor and increased levels of prostate
      specific antigen. Thirty-nine (97%) of 40 patients with cancer had either
      sonographic findings suggestive of tumor or increased prostate-specific antigen
      density, and one (3%) had no evidence of tumor on sonography and a normal
      prostate-specific antigen density. CONCLUSION: Directed and random sonographic
      biopsies of the prostate are indicated in patients with sonographic findings
      suggestive of tumor and increased prostate-specific antigen density and in
      patients with abnormal sonographic findings and normal prostate-specific antigen
      density. Random biopsies are indicated in patients with normal sonographic
      findings and increased prostate-specific antigen density. In our series, random
      biopsies were not indicated in 25 of 26 patients with normal sonographic findings
      and normal prostate-specific antigen density. Further research on the need for
      random biopsies when there are no sonographic abnormalities and when prostate
      specific antigen densities are not elevated is warranted.

PMID- 7527613
TI  - [Dose intensity in M-VAC chemotherapy with rG-CSF for metastatic transitional
      urothelial cancer].
AB  - The effect of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin)
      chemotherapy supported recombinant human granulocyte stimulating factor (rG-CSF)
      was studied in 18 patients with metastatic urothelal cancer. The mean age of the
      patients was 66 years. Of the patients 6 had lung metastasis and 12 had distant
      lymph node metastasis. In this study recombinant human granulocyte stimulating
      factor was administered therapeutically at 100 to 250 micrograms subcutaneously
      after the white blood cell count was less than 3,000/mm. Relative dose-intensity
      (RDI) was 0.88 +/- 0.11 and 0.72 +/- 0.19 for 11 patients with rG-CSF and 7
      without rG-CSF, respectively. The relative dose regardless of the interval of the
      cycle of M-VAC chemotherapy (%Dose) was 0.95 +/- 0.06 and 0.86 +/- 0.09 for the
      patients with rG-CSF and those without rG-CSF, respectively. Of seven patients
      without rG-CSF 3 patients responded (response rate 42%, mean survival period 7.4
      months). Of 11 patients treated with rG-CSF 3 patients responded (response rate
      72.7%, mean survival period 20.0 months). Although rG-CSF increased the RDI of M
      VAC chemotherapy, the correlation of response with RDI was not clearly
      demonstrated. The therapeutical administrations of rG-CSF fail to improve the
      mean white blood cell nadir and to prevent the decrease of the platelet and
      reticulocyte count.

PMID- 7527615
TI  - Recent advances in the application of hypnosis to pain management.
AB  - In this paper I examine the clinical use of hypnosis for pain management from a
      cognitive-behavioral perspective. This perspective emphasizes the multifaceted
      nature of hypnotic interventions and the importance of patients' attitudes,
      expectations, and beliefs in modulating the pain experience. Special attention is
      given to identifying ways of combining cognitive and contextual variables to
      maximize clinical outcomes. Since this approach does not pivot around the concept
      of a hypnotic trance state, we look elsewhere in our quest to understand the
      nature of pain modulation in the hypnotic context. Freedom from a theoretical
      commitment to the hypnotic trance state is seen as opening new avenues for the
      development of effective clinical interventions.

PMID- 7527616
TI  - Apoptosis of vascular smooth muscle cells. Protein kinase C and oncoprotein Bcl-2
      are involved in regulation of apoptosis in non-transformed rat vascular smooth
      muscle cells.
AB  - We examined the effect of several inhibitors/activators of various protein
      kinases on the proliferation and apoptosis of nontransformed rat coronary
      vascular smooth muscle cells (SMC). As expected, all the compounds (calphostin C,
      KT5720, KT5823, verapamil, W7, and dibutyryl-cAMP) inhibited SMC proliferation,
      as judged by [3H]thymidine incorporation. Three (calphostin C, verapamil and
      dibutyryl-cAMP) of the six compounds caused occurrence of the classical apoptotic
      morphology in SMC. The effect of calphostin C, an inhibitor of protein kinase C,
      was examined in more detail due to the known involvement of this kinase in
      regulation of apoptosis in a variety of cell types. In SMC cultures exposed for
      1, 2, and 3 days to 0.1 mumol/L calphostin C, 7 +/- 1%, 32 +/- 3%, and 29 +/- 3%
      of cells underwent apoptosis, respectively, as assessed by cell morphology
      (control cultures had 1 to 3% of apoptotic cells). The effect of calphostin C was
      transient in that on day 6 following exposure to this compound the number of
      apoptotic cells declined to control values. Simultaneous with the induction of
      apoptotic morphology in SMC, a decline was seen (within 24 hours) in expression
      of the oncoprotein Bcl-2 in morphologically nonapoptotic SMC. An altered
      distribution of Bcl-2 was seen in the apoptotic cells. The calphostin C-induced
      generation of apoptotic cells in SMC cultures and the decline/alteration of Bcl-2
      expression were not accompanied by degradation of DNA into nucleosomal fragments.
      In conclusion, normal, nontransformed rat coronary artery vascular SMC undergo
      apoptosis when exposed to an inhibitor of protein kinase C (calphostin C), to a
      calcium channel blocker (verapamil), and to a stimulator of cAMP-dependent
      protein kinase (dibutyryl-cAMP). The induction of apoptosis by the inhibitor of
      protein kinase C is accompanied by alterations in the Bcl-2 expression but not by
      DNA fragmentation.

PMID- 7527619
TI  - Melatonin, a hormone monitorable in vivo by voltammetry?
AB  - Melatonin, an indoleamine hormone synthesized in the pinealocytes, is
      electroactive at the surface of pre-treated carbon fibre microelectrodes (mCFE)
      in vitro when using differential-pulse voltammetry (DPV), at the specific
      oxidation potential of approximately +570 mV. In vivo DPV experiments have then
      been performed in melatonergic regions such as the pineal gland or the
      suprachiasmatic nucleus (SCH) of anaesthetized adult male rats. These experiments
      indicated the feasibility of simultaneous measurements of the indolaminergic peak
      3, which occurred at approximately +280 mV, due mainly to the oxidation of
      extracellular 5-hydroxyindoleacetic acid (5HIAA), and a signal at approximately
      +580 mV which we called peak M. Pharmacological in vivo experiments performed in
      anaesthetized rats prepared for DPV analysis with the mCFE implanted into the
      pineal gland or the SCH indicated that intravenous or intra-cerebral injections
      of exogenous melatonin (5 mg kg-1 or 2 micrograms microliter-1, n = 3,
      respectively) were followed by a selective and significant increase of in vivo
      peak M. Other in vivo experiments with anaesthetized rats prepared for DPV
      analysis with the mCFE into the SCH showed that tryptophan [TRY, 30 mg kg-1
      intravenous (i.v.), n = 3] and n-acetyl serotonin (nA-5HT, 5 mg kg-1 i.v., n =
      3), both precursors of melatonin, were responsible for a transient but
      significant increase in the size of peak M (approximately 320% or 126% of control
      levels within 10 min or 20 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527617
TI  - Reverse transcriptase polymerase chain reaction for the Ki-1 anaplastic large
      cell lymphoma-associated t(2;5) translocation in Hodgkin's disease.
AB  - Hodgkin's disease (HD) and Ki-1 positive anaplastic large cell lymphoma (Ki-1
      ALCL) appear pathologically and immunohistochemically related, and a common
      histogenesis has been postulated in at least some cases. The breakpoints of the
      t(2;5) (p23;q35) [corrected] translocation, which is reported in about 40% of Ki
      1 ALCL, have recently been cloned. They involve a novel tyrosine kinase gene,
      ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse transcriptase
      polymerase chain reaction (RT-PCR) using NPM and ALK primers consistently detects
      a fusion product in Ki-1 ALCL cases with the translocation. To determine if this
      tumor-specific genetic alteration also occurs in HD, we performed NPM-ALK RT-PCR
      on RNA samples extracted from 40 lymph node biopsies of HD (25 nodular sclerosis,
      11 mixed cellularity, 2 lymphocyte depleted, 2 lymphocyte predominant). Using
      control samples, the sensitivity of the NPM-ALK RT-PCR assay was shown to be at
      least 1:10(4). Amplifiable template was confirmed in all samples by RT-PCR using
      beta-actin primers. None of the 40 cases showed the expected 177-bp RT-PCR
      product indicative of the translocation. We conclude that the most common primary
      genetic alteration in Ki-1 ALCL, the t(2;5), is absent or very infrequent in
      typical cases of HD. These results further support the concept that HD and Ki-1
      ALCL are pathogenetically distinct entities.

PMID- 7527620
TI  - Effects of isoflurane on ouabain toxicity in canine Purkinje fibers. Comparison
      with halothane.
AB  - BACKGROUND: Although halothane reduces digitalis toxicity, other anesthetics,
      notably cyclopropane, increase toxicity. This study determined the effects of
      isoflurane on digitalis toxicity in isolated cardiac tissue and compared these
      effects with those of halothane. METHODS: Standard microelectrode techniques were
      used to record action potentials from excised canine Purkinje fibers. Fibers were
      paced at cycle lengths between 1,000 and 250 ms for 20 beats to induce delayed
      afterdepolarizations, which are membrane potential oscillations indicative of
      intracellular Na+ and Ca2+ overload, produced in these experiments by digitalis
      toxicity. The digitalis glycoside ouabain, 2 x 10(-7) M, was added to the
      Tyrode's solution superfusate to induce delayed after-depolarizations. Action
      potential variables and the coupling interval and amplitude of
      afterdepolarizations were then measured. Isoflurane (0.5%, 1%, or 2%) was added
      with a calibrated vaporizer (n = 8). In a second set of experiments (n = 10),
      isoflurane 1.25% or halothane 0.75% was added to the superfusate. After
      measurements had been made, the other agent was substituted. RESULTS: Ouabain
      produced primary and secondary delayed afterdepolarizations, which were reduced
      in amplitude by isoflurane in a dose-related manner (P = 0.0002). Action
      potential duration to 90% repolarization was shortened by ouabain (P = 0.009) and
      remained shortened during isoflurane administration. Action potential duration to
      50% repolarization was shortened by isoflurane 2%. Halothane and isoflurane were
      equally effective in reducing the amplitude of delayed afterdepolarizations (both
      P = 0.0002). In three fibers, triggered extrasystoles appeared. Halothane and
      isoflurane each abolished extrasystoles. In two fibers, sustained triggered
      activity appeared. Isoflurane abolished the arrhythmia in each fiber.
      CONCLUSIONS: Isoflurane and halothane are equally effective in reducing delayed
      afterdepolarizations induced by ouabain toxicity.

PMID- 7527618
TI  - Protein and mRNA expression of simple epithelial keratins in normal, dysplastic,
      and malignant oral epithelia.
AB  - Simple epithelial keratins K7, K8, and K18 are present in no more than trace
      amounts in normal stratified squamous epithelial but have been reported in
      squamous cell carcinomas. With the aim of determining the level at which keratin
      synthesis is regulated in vivo, we have compared the expression of mRNA by in
      situ hybridization and protein by immunohistochemistry for K7, K8, and K18 in a
      series of normal, dysplastic, and malignant oral epithelia. In normal epithelia
      mRNAs for K7, K8, and K18 were present in basal and lower spinous cells but
      adjacent sections were generally negative for the respective proteins. In severe
      dysplasia there was irregular suprabasal extension of K8 and K18 mRNAs in all
      cases and their proteins were expressed in more than half of the cases. The
      carcinomas expressed K8 and K18 mRNAs homogeneously and were strongly reactive
      for these keratin proteins but K7 expression appeared reduced in malignancy.
      These results are consistent with the post-transcriptional regulation of K7, K8,
      and K18 expression in normal epithelia and the presence of their proteins in
      dysplastic and malignant epithelia suggests the release of these epithelial cells
      from a post-transcriptional block on K8 and K18 translation. Alternatively, rapid
      degradation of K8 and K18 protein might be occurring in normal epithelia but be
      suppressed in dysplasia and malignancy.

PMID- 7527622
TI  - The impact of immunology and molecular biology on clinical practice.

PMID- 7527621
TI  - [Rejection of a liver allograft. Diagnosis and treatment].
AB  - Graft rejection remains a major problem in liver transplantation. The frequency
      of acute rejection is of the order of 50%. The first episode usually occurs
      around the 7th day. The diagnosis, suggested by clinical signs and biochemical
      abnormalities, is confirmed by histology. Three fundamental histological lesions
      are usually observed: portal infiltrate, biliary lesions and endothelitis.
      Chronic liver rejection is characterised by progressive reduction in the number
      of interlobular bile ducts. It affects 5 to 15% of transplant recipients, is
      refractory or poorly responsive to current immunosuppressant treatments and
      usually requires retransplantation. Prophylactic immunosuppression usually
      consists of a triple combination of cyclosporin-azathioprine-corticosteroids. FK
      506 has been recently proposed. Corticosteroids inhibit the synthesis of
      interleukin 1 and reduce the synthesis of mediators of inflammation. Azathioprine
      is an antimetabolite which inhibits T lymphocyte cell division. Cyclosporin
      decreases lymphokine secretion. FK 506 can be used to treat acute rejection
      resistant to other immunosuppressants and may prevent chronic rejection.
      Cyclosporin is started at low doses and gradually increased until the desired
      serum concentration is obtained. Regular monitoring of serum cyclosporin levels
      is essential to reduce the adverse effects of this drug. The doses of
      corticosteroids are gradually decreased to achieve a maintenance dose (10-30
      mg/day). Azathioprine is commenced postoperatively (0.5 to 1.5 mg/kg/day). In the
      long term, azathioprine should be suspended and the dosage of corticosteroids
      should be reduced. The initial treatment of rejection consists of bolus
      injections of corticosteroids: 10 to 15 mg/kg/day of i.v. methylprednisolone for
      2 or 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527623
TI  - Genetic relationships among the Native American populations.
AB  - Red cell antigen data were used to investigate the genetic relationship among the
      Native American populations and their affinities with Siberian and Eastern Asian
      populations. Correspondence analysis showed a clear subdivision of all the Native
      American populations into three clear-cut clusters corresponding to the three
      linguistic families (identified by Greenberg)--Amerind, Na-Dene and Eskimo-Aleut.
      This result, as well as the close genetic resemblance between the Eskimos and the
      Asian populations, support the conclusion that the Americas were populated during
      at least three distinct and subsequent migration waves of people coming from
      Asia.

PMID- 7527624
TI  - Differential expression patterns of type I interferon subtypes in mouse embryo
      fibroblasts: influence of genotype and viral inducer.
AB  - Primary mouse embryo fibroblasts from 4 strains of mice (BALB/c, C57Bl/6, B6.C-H
      28c and CBA) were infected with either Newcastle disease virus or murine
      cytomegalovirus. The time course of the total type I interferon response was
      assessed and the presence of individual subtypes determined. The total type I
      interferon produced was titrated using the cytopathic effect reduction assay and
      the relative levels of type I interferon subtypes expressed (alpha 1, alpha 4,
      alpha 5, alpha 6 and beta) were evaluated using a reverse transcription
      polymerase chain reaction-based technique. In general, the patterns of type I
      interferon subtypes expressed appeared to be determined by the strain of mouse
      cells used rather than the inducing virus. However, the overall titre of type I
      interferons produced in response to a given virus was quite uniform across the
      strains of mice from which the mouse embryo fibroblasts were derived regardless
      of the subtype expression pattern. The latter observation fits the proposition
      that "cross-talk" or feedback between the type I interferon genes and their
      products is is occurring and that the inducer determines the level of response.

PMID- 7527625
TI  - merA gene expression in aquatic environments measured by mRNA production and
      Hg(II) volatilization.
AB  - The relationship of merA gene expression (specifying the enzyme mercuric
      reductase) to mercury volatilization in aquatic microbial communities was
      investigated with samples collected at a mercury-contaminated freshwater pond,
      Reality Lake, in Oak Ridge, Tenn. Levels of merA mRNA transcripts and the rate of
      inorganic mercury [Hg(II)] volatilization were related to the concentration of
      mercury in the water and to heterotrophic activity in field samples and
      laboratory incubations of pond water in which microbial heterotrophic activity
      and Hg(II) concentration were manipulated. Levels of merA-specific mRNA and
      Hg(II) volatilization were influenced more by microbial metabolic activity than
      by the concentration of mercury. merA-specific transcripts were detected in some
      samples which did not reduce Hg(II), suggesting that rates of mercury
      volatilization in environmental samples may not always be proportional to merA
      expression.

PMID- 7527628
TI  - Production of some extracellular enzymes by a lignin peroxidase-producing brown
      rot fungus, Polyporus ostreiformis, and its comparative abilities for lignin
      degradation and dye decolorization.
AB  - Polyporus ostreiformis produced Mn peroxidase, acid protease, alpha-amylase, and
      lignin peroxidase, with maximum activities of 40, 8,300, and 4,200 U liter-1 and
      50 nkat liter-1, respectively, in nitrogen-limited liquid media. The fungus
      removed only 18.6% lignin from rice straw in 3 weeks but effected 99%
      decolorization of Congo red dye in 9 days.

PMID- 7527626
TI  - Nucleotide sequence and functional analysis of the genes encoding 2,4,5
      trichlorophenoxyacetic acid oxygenase in Pseudomonas cepacia AC1100.
AB  - Pseudomonas cepacia AC1100 is able to use the chlorinated aromatic compound 2,4,5
      trichlorophenoxyacetic acid (2,4,5-T) as the sole source of carbon and energy.
      One of the early steps in this pathway is the conversion of 2,4,5-T to 2,4,5
      trichlorophenol (2,4,5-TCP). 2,4,5-TCP accumulates in the culture medium when
      AC1100 is grown in the presence of 2,4,5-T. A DNA region from the AC1100 genome
      has been subcloned as a 2.7-kb SstI-XbaI DNA fragment, which on transfer to
      Pseudomonas aeruginosa PAO1 allows the conversion of 2,4,5-T to 2,4,5-TCP. We
      have determined the directions of transcription of these genes as well as the
      complete nucleotide sequences of the genes and the number and sizes of the
      polypeptides synthesized by pulse-labeling experiments. This 2.7-kb DNA fragment
      encodes two polypeptides with calculated molecular masses of 51 and 18 kDa.
      Proteins of similar sizes were seen in the T7 pulse-labeling experiment in
      Escherichia coli. We have designated the genes for these proteins tftA1 (which
      encodes the 51-kDa protein) and tftA2 (which encodes the 18-kDa protein). TftA1
      and TftA2 have strong amino acid sequence homology to BenA and BenB from the
      benzoate 1,2-dioxygenase system of Acinetobacter calcoaceticus, as well as to
      XylX and XylY from the toluate 1,2-dioxygenase system of Pseudomonas putida. The
      Pseudomonas aeruginosa PAO1 strain containing the 2.7-kb SstI-XbaI fragment was
      able to convert not only 2,4,5-T to 2,4,5-TCP but also 2,4-dichlorophenoxyacetic
      acid to 2,4-dichlorophenol and phenoxyacetate to phenol.

PMID- 7527627
TI  - Expression of tfx and sensitivity to the rhizobial peptide antibiotic
      trifolitoxin in a taxonomically distinct group of alpha-proteobacteria including
      the animal pathogen Brucella abortus.
AB  - Three phylogenetically distinct groups within the alpha-proteobacteria which
      differ in trifolitoxin sensitivity are described. Trifolitoxin sensitivity was
      found in strains of Agrobacterium, Brucella, Mycoplana, Ochrobactrum,
      Phyllobacterium, Rhodobacter, Rhodopseudomonas, Rhodospirillum, and Rhizobium.
      Strains of Agrobacterium, Brucella, Phyllobacterium, Rhizobium, and
      Rhodospirillum were capable of producing trifolitoxin upon conjugal transfer of
      tfxABCDEFG.

PMID- 7527629
TI  - Urinary excretion of thromboxane and markers for renal injury in patients
      undergoing cardiopulmonary bypass.
AB  - Urinary excretion of selected markers for renal injury, as well as urinary
      excretion rates of the thromboxane metabolite, 11-keto-thromboxane B2 (11k-TXB2),
      was studied in 36 male patients undergoing coronary bypass surgery using
      cardiopulmonary bypass (CPB). In all patients, excretion of both tubular (N
      acetyl-beta-D-glucosaminidase [beta NAG]; alpha 1-microglobulin [alpha 1-MG]) and
      glomerular markers (albumin [Alb]; transferrin [Trf]; immunoglobulin G [IgG])
      sharply increased on Day 1 after CPB, and they remained elevated throughout the
      observation period of 5 days. Urinary excretion rates of 11k-TXB2 markedly
      increased on Day 1 after surgery, and they rapidly decreased thereafter. In 12 of
      the 36 patients, a temporary increase of serum creatinine levels (> 1.30 mg/dl)
      was noted following surgery. A positive correlation was found between serum
      creatinine levels and excretion of the tubular enzyme beta NAG (r = 0.36; p <
      0.05), but not between creatinine levels and alpha 1-MG or the glomerular
      markers. Furthermore, no correlation between urinary excretion of 11k-TXB2 and
      any of the urinary markers for renal injury could be detected. Our data do not
      strengthen the hypothesis that acute renal injury observed during CPB is related
      to exaggerated thromboxane biosynthesis in these patients. Monitoring of urinary
      markers for incipient renal damage, particularly excretion of beta NAG, might be
      of additional diagnostic value for detection of otherwise subclinical renal
      injury in patients undergoing CPB.

PMID- 7527630
TI  - Detecting recurrent choroidal neovascularization. Comparison of clinical
      examination with and without fluorescein angiography.
AB  - OBJECTIVE/DESIGN: To evaluate prospectively the ability of three retina
      specialists to detect recurrent choroidal neovascularization (CNV) after clinical
      examination alone and then with fluorescein angiography at 3 and 6 weeks and at
      3, 6, 9, and 12 months after laser photocoagulation. SETTING: Single tertiary
      retinal referral center. PATIENTS: All patients who had laser treatment for CNV
      within 14 months of their study visit. One hundred thirty-seven eyes of 134
      patients were evaluated during 401 visits. MAIN OUTCOME MEASURES: Sensitivity,
      specificity, positive predictive value, and negative predictive value of clinical
      examination with biomicroscopy to detect recurrent CNV when defined as leakage on
      the periphery of the laser-treated area on the fluorescein angiogram. RESULTS:
      Ninety-seven definite or probable recurrences in 56 eyes were identified on the
      fluorescein angiogram. Clinical examination had a sensitivity of 59%, specificity
      of 94%, positive predictive value of 76%, and negative predictive value of 88%.
      These figures varied somewhat by underlying cause, age, time since treatment, and
      lesion location. Using either a reported or measured loss of vision with the
      results of biomicroscopy as an indication of recurrence increased the sensitivity
      to 77% but reduced the specificity to 81%. CONCLUSIONS: Clinical examination
      probably cannot replace fluorescein angiography in detecting all recurrent CNV
      after laser treatment. However, for follow-up visits in which recurrent CNV was
      not suspected on biomicroscopy, definite or questionable recurrent CNV was
      identified on the fluorescein angiogram only 12% of the time, while the absence
      of recurrent CNV using this method was confirmed 88% of the time.

PMID- 7527631
TI  - Treatment of keratoconjunctivitis sicca in rabbits with 3-isobutyl-1
      methylxanthine.
AB  - OBJECTIVE: To examine the effects of topical 3-isobutyl-1-methylxanthine
      treatment on tear-film osmolarity, conjunctival goblet-cell densities, and
      corneal epithelial glycogen levels in a rabbit model for keratoconjunctivitis
      sicca. METHODS: Keratoconjunctivitis sicca was surgically induced in the right
      eyes of 16 rabbits. In a masked protocol, eight of these operated-on eyes
      underwent treatment for 12 weeks with a 3.0-mmol solution of 3-isobutyl-1
      methylxanthine. The remaining eight operated-on eyes were left untreated and
      served as controls. RESULTS: The 3-isobutyl-1-methylxanthine treatment resulted
      in a rapid and significant decrease in tear osmolarity and sodium (P < .5) and
      potassium levels (P < .05) and a significant increase in conjunctival goblet-cell
      densities and corneal epithelial glycogen levels compared with untreated and
      operated-on controls (P < .001). CONCLUSIONS: 3-Isobutyl-1-methylxanthine rapidly
      and significantly decreased tear-film osmolarity in this rabbit model for
      keratoconjunctivitis sicca and restored conjunctival goblet-cell densities and
      corneal glycogen levels, thus reversing the disease process.

PMID- 7527633
TI  - Chronic administration of neurokinin SP improves maze performance in aged Rattus
      norvegicus.
AB  - Deficits in associative functions seen with senescence may be based, at least in
      part, on a decreased availability of trophic factors in the CNS. A reduced
      concentration of neurokinins, including undecapeptide substance P (SP), also
      accompanies aging. Thus, given the change in SP metabolism and the known
      mnemogenic as well as neurotrophic/neuroprotective effects of the peptide, it
      seems possible that age-related deficits in associative processes could be
      influenced by treatment with exogenous SP. In the present study, 30-month-old
      Wistar rats were injected daily with SP (50 or 250 micrograms/kg,
      intraperitoneally) starting 1 week before they were tested on the Morris water
      maze task and on motor coordination tests. Control groups included vehicle
      injected old and adult (3-month-old) rats. Over the days of maze testing,
      application of the substances was performed 5 h after testing daily for 15 days
      and after the last drug delivery, maze testing was continued for 4 more days. The
      main finding of this study is that chronic administration of both dosages of SP
      (50 and 250 micrograms/kg) improved the maze performance of the old rats. This
      facilitatory effect of SP on performance was also evident after the drug
      treatment had been terminated in the course of maze testing. Furthermore, chronic
      application of SP in a dose range of 50-250 micrograms/kg was found to reduce age
      related deficits in motor capacities.

PMID- 7527632
TI  - Viruses and schizophrenia.
AB  - A viral hypothesis for the pathogenesis of schizophrenia has been under serious
      consideration for more than 70 years. To date, attempts have failed to identify a
      specific virus which contributes to the aetiology of the disorder. There has,
      however, been a recent resurgence of interest in a possible relationship between
      viral illness and schizophrenia. This renewed attention is the result of
      epidemiological evidence suggesting an excess of winter births in patients with
      schizophrenia, indications of foetal insults in persons who develop schizophrenia
      and an association between foetal exposure to the influenza virus and the
      subsequent development of schizophrenia. Advances in our understanding of the
      pathophysiology of viral diseases and the development of sophisticated techniques
      to study them have resulted in more complex viral hypotheses of schizophrenic
      aetiology, such as viral disruption of normal neurodevelopment, viral induced
      autoimmunity and retroviral integration. These hypotheses are now beginning to be
      tested experimentally.

PMID- 7527634
TI  - [Modeling antigenic determinants of the hepatitis A virus using synthetic
      peptides].
AB  - Monoclonal and polyclonal anti-hepatitis A (HAV) antibodies were used to search
      for peptides mimicking the antigenic determinants of HAV. Synthetic peptides VP1
      115-139, VP1 117-139, VP1 126-139, VP2 69-99, VP2 80-99, VP3 45-57, VP3 137-150,
      were shown to bind the anti-HAV antibodies in ELISA. Peptides VP1 115-139, VP1
      117-139, VP2 69-99 were utilized to produce the antipeptide antibodies. Mice were
      immunized with the free peptides or with their conjugates with ovalbumin. Only
      the free VP2 69-99 caused formation of HAV binding antibodies.

PMID- 7527635
TI  - [Interaction of substance P receptor from rat brain with antibodies to its
      synthetic fragments and to substance P].
AB  - The peptides which correspond to the fragments 55-64, 182-192, 225-236 and 236
      245 (P1-P4, respectively) of the rat brain substance P receptor were synthesized.
      Antibodies (Ab1-Ab4, respectively) against the KLH-conjugates of these peptides
      were raised and purified by affinity chromatography. None of the antibodies
      inhibited the Bolton-Hunter labelled substance P, [125I]BH-SP, binding to the rat
      brain membranes. On the other hand, Ab2 and Ab3 recognition of the SP receptor
      was found in ELISA experiments: the CHAPS--solubilized rat brain membranes could
      inhibit binding of these antibodies to the immobilized P2 and P3. Antibodies Ab1
      Ab4 did not interact with the CHAPS-solubilized DDS cross-linked complex of the
      [125I]BH-SP and SP receptor. However, this complex retained the capacity of
      interacting with the affinity-purified antibodies against SP and was purified by
      sequential gel-permeation HPLC and protein A-chromatography.

PMID- 7527636
TI  - [(252)Cf-plasma desorption mass spectra of bacterial oligosaccharides].
AB  - 252Cf plasma desorption mass spectrometry on a "reflect" desorption instrument
      (MSBX) was used to study oligosaccharides from bacterial O-specific antigenic
      chains. The data obtained for galacturonic acid, neutral and aminouronic
      oligosaccharides are discussed. This method is suggested for determining the
      composition of oligosaccharides from the O-specific polysaccharides and for
      elucidating their structures after modifications.

PMID- 7527637
TI  - The superior effect of the combination of FK 506 and deoxyspergualin on rat
      cardiac allograft survival.
AB  - In this present study, the effects of FK 506 and 15-deoxyspergualin (DSG), with
      respect to dose, timing, and combination, were investigated in an ACI-to-LEW rat
      cardiac allograft model. FK 506 was administered intramuscularly for 14 days
      starting on day 0 after grafting, while DSG was given intraperitoneally for 7
      days starting on day 0,4, or 7 after transplantation. FK 506 or DSG monotherapy
      prolonged cardiac allograft survival in dose-dependent manners, and the minimum
      effective dose for overcoming rejection was 0.1 mg/kg per day in the case of FK
      506 and 1.0 mg/kg per day for DSG. The graft survival rate was higher with
      administration of DSG starting on day 4 on day 0 after transplantation. A low
      dosage of FK 506 starting on day 0, in combination with DSG starting on day 0 or
      day 4 (but not on day 7), had a synergistic effect in prolonging allograft
      survival for 14.0 +/- 3.3 days and 25.4 +/- 8.2 days, respectively. The most
      effective combination treatment schedule for prolongation of allograft survival
      was FK 506 starting on day 0 and DSG starting on day 4 after transplantation.

PMID- 7527638
TI  - The use of plasma levels for FK 506 dosing in liver-grafted patients.
AB  - FK 506 plasma levels were analyzed in 89 liver-grafted patients under FK 506
      based immunosuppression. Plasma levels were found to be influenced by the
      patients' liver function: compared to patients without major liver dysfunction,
      those with cholestasis had higher plasma levels and these plasma levels were able
      to differentiate between rejection and toxicity. In patients with stable liver
      function, no clear difference was observed with regard to the plasma levels
      detectable during toxicity or rejection. We conclude that plasma levels can be
      used to determine the FK 506 dose but only in patients with cholestasis (i.e.,
      during the early post-transplant course, or in patients with cholestatic
      rejection). In patients with stable liver function, plasma levels are only of
      limited clinical relevance.

PMID- 7527640
TI  - FK 506 as an alternative in cyclosporin-induced hemolytic uremic syndrome in a
      kidney transplant recipient.
AB  - We describe a patient who received a living related kidney transplant that worked
      very well initially but developed oliguria and renal failure within 1 week and
      required dialysis. Clinical and hemological changes, as well as renal biopsy,
      confirmed the diagnosis of cyclosporin-induced hemolytic uremic syndrome. The
      patient did not respond to antirejection therapy or plasma exchange but did
      respond to the withdrawal of cyclosporin A and the commencement of FK 506.

PMID- 7527639
TI  - Sensitivity of baboon lymphocytes to cyclosporin A and FK 506: relative
      resistance of alloactivated cells to CyA.
AB  - The interspecies differences in CyA pharmacokinetics necessitate the
      establishment of optimal immunosuppressive doses in the baboon, especially as its
      use as host for preclinical xenografts is anticipated. We assessed the
      immunosuppressive effects of CyA and FK 506 on lymphocytes from chacma baboons,
      using human cells for comparison. At concentrations up to 100 mumol/l, neither
      drug was toxic to lymphocytes. FK 506 inhibited baboon and human lymphocyte
      proliferation and IL-2 synthesis equally. In contrast, approximately four times
      higher doses of CyA were needed to inhibit baboon lymphocytes responding to
      alloantigens. This may explain the inadequate immunosuppression of baboon graft
      recipients treated with clinically acceptable doses of CyA. We propose that CyA
      whole blood target levels of +/- 1500 ng/ml should be used in this species and we
      provide evidence that chacma baboons are able to tolerate such doses without
      nephrotoxicity.

PMID- 7527641
TI  - Agonist selectivity of glutamate receptors is specified by two domains
      structurally related to bacterial amino acid-binding proteins.
AB  - By exchanging portions of the AMPA receptor subunit GluR3 and the kainate
      receptor subunit GluR6, we have identified two discontinuous segments of
      approximately 150 amino acid residues each that control the agonist pharmacology
      of these glutamate receptors. The first segment (S1) is adjacent and N-terminal
      to the putative transmembrane domain 1 (TM1), whereas the second segment (S2) is
      located between the putative TM3 and TM4. Only the simultaneous exchange of S1
      and S2 converts the pharmacological profile of the recipient to that of the donor
      subunit. The two segments identified in this study share sequence similarities
      with the ligand-binding site of several bacterial periplasmic amino acid-binding
      proteins. Based on the X-ray structure of these proteins, we propose a model for
      the glutamate-binding site of ionotropic glutamate receptors.

PMID- 7527642
TI  - Has combined modality therapy improved the outlook in carcinoma of the esophagus?
AB  - Carcinoma of the esophagus or the gastroesophageal junction is uncommon,
      accounting for approximately 1% of all malignancies in the United States.
      Approximately 11,000 new cases and 10,400 deaths are estimated in 1994. The
      diagnosis is often made late in Western countries, thus T3, T4, and N-positive
      lesions are encountered frequently. Nearly 50% of patients have advanced
      incurable disease at the time of diagnosis. Therefore, the prognosis of patients
      with carcinoma of the esophagus remains poor and the overall 5-year survival
      rates are still under 10%. The answer to the question in the title is yes, at
      least for some patients, on a short-term basis.

PMID- 7527644
TI  - The plasma concentration of soluble Fc-gamma RIII is related to production of
      neutrophils.
AB  - Fc gamma RIII (the CD16-antigen), a low-affinity receptor for IgG, is expressed
      by neutrophils, natural killer lymphocytes and macrophages. A soluble form of Fc
      gamma RIII has been identified in human plasma. This soluble form of Fc gamma
      RIII (sFc gamma RIII) originates from release by neutrophils. In the present
      study we show by transfusions of plasma that contains sFc gamma RIII of one
      allotype (NA1-Fc gamma RIII) in recipients homozygous for the other allotype (NA2
      Fc gamma RIII) that the clearance of sFc gamma RIII is about 0.7 ml/min. Because
      the concentration of sFc gamma RIII was found to be constant in a small cohort of
      donors followed for about 1.5 years, the half-life of NA1-sFc gamma RIII is about
      1.8 d, assuming a one-compartment model. The plasma concentration of sFc gamma
      RIII depended mainly on the production of neutrophils in the bone marrow, and was
      not influenced by shifts of neutrophils from one pool to another (storage,
      marginating or circulating pool). Because Fc gamma RIII is only expressed on
      mature neutrophils, this implies that the concentration of sFc gamma RIII depends
      on production of mature neutrophils.

PMID- 7527643
TI  - Propagation of large numbers of T cells with natural killer cell markers.
AB  - Previously, a subset of T cells co-expressing the NK cell antigen CD56 has been
      described. These CD3+CD56+ cells are rare in peripheral blood collections and
      have been poorly characterized. We have developed culture conditions which allow
      for the rapid expansion of CD3+CD56+ cells. The protocol for cellular expansion
      includes the addition of interferon-gamma on day 0, interleukin-1, interleukin-2
      and a monoclonal antibody against CD3 on day 1 to peripheral blood lymphocytes.
      Cells of the CD3+CD56+ phenotype increased up to 6000-fold using this protocol
      after 16 d in culture. These cells have been characterized by flow cytometry and
      have been found to express the alpha, beta T cell receptor, co-express the CD5
      and CD8 antigens and do not express the CD16 antigen. Morphologically, these
      cells cannot be distinguished from NK cells. CD3+CD56+ killer cells lyse a
      variety of tumour cells with intermediate activity between CD3-CD56+ NK cells and
      CD3+CD56- T cells.

PMID- 7527645
TI  - Bone marrow angiogenesis and progression in multiple myeloma.
AB  - Tumour growth is angiogenesis-dependent. We found a high correlation between the
      extent of bone marrow angiogenesis, evaluated as microvessel area, and the
      proliferating (S-phase) fraction of marrow plasma cells, evaluated as labelling
      index (LI), in patients with multiple myeloma (MM) and in those with monoclonal
      gammopathies of undetermined significance (MGUS). Angiogenesis itself was
      significantly associated with active as opposed to non-active MM and MGUS. The
      highest microvessel area accompanied rapidly progressive MM with the highest LI.
      When a cut-off value of 2% or greater of the microvessel area was used, most
      patients with active MM were classified correctly. The risk of active disease in
      patients with MM increased in parallel with the microvessel area. A causal
      relationship between plasma cell growth, activity phase in MM and marrow
      angiogenesis is suggested. Since angiogenesis proceeds in step with the
      enlargement of plasma cell tumours and the activity phase in MM, its measurement
      could be a useful prognostic marker in patients with plasma cell proliferative
      disorders.

PMID- 7527646
TI  - Peripheral T-cell non-Hodgkin's lymphomas of low malignancy: prospective study of
      25 patients with pleomorphic small cell lymphoma, lymphoepitheloid cell
      (Lennert's) lymphoma and T-zone lymphoma. The Kiel Lymphoma Study Group.
AB  - Peripheral T-cell lymphomas comprise a heterogenous group of low- and high-grade
      malignancies differing in their histopathological appearance and also in clinical
      and prognostic aspects. We prospectively studied 25 patients with low-grade
      peripheral T-cell lymphomas: pleomorphic, small cell lymphoma (PSC) (n = 9),
      lymphoepitheloid (Lennert's) lymphoma (LEL) (n = 12) and T-zone lymphoma (TZL) (n
      = 4). The median patient age was 55 years (range 19-75 years); the male to female
      ratio was 1.5. 13 patients (52%) had limited stages (I+II), 12 patients (48%) had
      advanced disease (stage III+IV). 21 patients received the COPBLAM/IMVP-16
      regimen. Two patients received more intensive treatments; two received less
      intensive therapy. Complete remissions were achieved in 16/25 patients (64%). The
      median observation time of surviving patients was 30 months (range 5-72 months).
      The actuarial overall survival and event-free survival at 2 years of 21 patients
      receiving COPBLAM/IMVP-16 were 69% and 35%, respectively. Intensive chemotherapy
      led to complete remissions in about 60% of the patients and to long-term disease
      free survival for one-third. The observed clinical courses illustrate the
      aggressive nature of PSC, LEL and TZL.

PMID- 7527647
TI  - Circulating cytokines in sickle cell patients during steady state.
AB  - Plasma levels of GM-CSF, IL-3, IL-6 and IL-1 (alpha,beta) were investigated in
      steady-state sickle cell patients. We find that SS patients with low levels of
      HbF (< 9% [LFSS]) are characterized by elevated plasma GM-CSF, whereas in
      patients with high levels of HbF (HFSS), GM-CSF is not detectable. In contrast,
      HFSS patients exhibited increased plasma IL-3 (m = 84.8 +/- 57 pg/ml), whereas
      LFSS patients had lower or no detectable plasma IL-3, IL-1(alpha,beta) and IL-6
      were also detected in plasma from some SS patients, but there was no correlation
      with HbF levels. Normal controls tested negative for all cytokines, except for
      one individual positive for IL-3. These results are compatible with a model in
      which the level of haemopoietic stress determines the level of participation of
      GM-CSF or IL-3 in the regulation of SS circulating BFU-E.

PMID- 7527649
TI  - Anti-GMP140 (CD62) autoantibody in a patient with autoimmune thrombocytopenic
      purpura.
AB  - The presence of platelet GMP140 (CD62) antibodies was analysed by the MAIPA test
      in 57 sera from patients with AITP and on platelets from 54 patients with
      thrombocytopenia of suspected immune origin. A CD62 antibody was found in only
      one serum. Its specificity was confirmed by an ELISA and a
      radioimmunoprecipitation procedure using total intact platelets and immuno
      purified GMP140. An increased amount of platelet-associated (PA) IgG, due to in
      vivo fixation of GMP140 and GpIIb/IIIa antibodies, was also found on the patient
      platelet membrane. suggesting that GMP140 autoantibody may contribute to immune
      platelet destruction. No increase in PAGMP140 antibody was found on the other 54
      platelet suspensions.

PMID- 7527648
TI  - G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation:
      safety, kinetics of mobilization, and composition of the graft.
AB  - Allogeneic transplantation of peripheral blood progenitor cells (PBPC) makes the
      general anaesthesia of the donor unnecessary and may result in more rapid
      engraftment and faster recovery of the immune system. We have studied G-CSF
      mediated PBPC mobilization in healthy donors and analysed the cellular
      composition of the resulting PBPC grafts. PBPC grafts were obtained from nine
      healthy donors (18-67 years old) for allogeneic or syngeneic transplantation. Six
      donors received 10 micrograms/kg G-CSF per day, the others 5-6 micrograms/kg.
      Mobilization and harvesting were well tolerated except for moderate bone pain
      which occurred in all donors primed with 10 micrograms/kg. With 10 micrograms/kg,
      a 31-fold (9-62) enrichment of circulating CD34+ cells was observed with peak
      values constantly occurring on day 5 after the start of G-CSF administration.
      Starting harvest on day 5, one to three collections on consecutive days yielded
      5.5 x 10(6)/kg (0.9-10.7) CD34+ cells, 219 x 10(6)/kg (106-314) T cells, and 34 x
      10(6)/kg (23-67) NK cells per 10 litres leukapheresis volume. Altogether, PBPC
      grafts contained 3 times more CD34+ cells, 7 times more T cells, and 20 times
      more NK cells than five allogeneic marrow grafts that were analysed for
      comparison. The yield of CD34+ cells per 10 litres apheresis volume as well as
      the height of the CD34+ peak in peripheral blood were inversely correlated to the
      age of the donor. In the donors primed with 5-6 micrograms/kg G-CSF the increase
      of circulating CD34+ cells (4-7-fold enrichment) and the CD34+ cell yield per 10
      litres leukapheresis volume (1 x 10(6)/kg [0.8-2.2]) was much smaller compared
      with the 10 micrograms/kg group. In conclusion, sufficient amounts of PBPC
      capable of restoring haemopoiesis in allogeneic recipients can be mobilized
      safely by administration of G-CSF (10 micrograms/kg s.c. for 5 d) in healthy
      donors, and harvested with one or two leukapheresis procedures. Whether the large
      numbers of T-cells and NK cells that are contained in the collection products may
      influence graft-versus-host and graft-versus-leukaemia reactivities of PBPC
      grafts remains to be determined.

PMID- 7527650
TI  - Subpopulations of CD34-positive haemopoietic progenitors in fetal blood.
AB  - Flow cytometry was used to determine the percentage and number of circulating
      CD34+ cells in fetal blood from 100 pregnancies at 13-38 weeks gestation. When
      expressed as a percentage of the total number of lymphocytes, the proportion of
      CD34+ cells decreased exponentially from a mean of 11.1% (9.2 x 10(7)/l) at 13
      weeks to 1.0% (3.0 x 10(7)/l) at 38 weeks (r = 0.751, P < 0.0001). The use of
      primitive fetal blood CD34+ progenitor cells for prenatal somatic gene therapy
      may have distinct advantages over postnatal somatic gene therapy.

PMID- 7527651
TI  - Development of acute myeloblastic leukaemia in a case of aplastic anaemia treated
      with granulocyte colony-stimulating factor.
AB  - We report a case of aplastic anaemia (AA) treated with granulocyte colony
      stimulating factor (G-CSF) terminating as acute myeloblastic leukaemia (AML).
      Because of severe pneumonia, 250 micrograms of G-CSF was administered for 30 d to
      promote neutrophil recovery. Following G-CSF therapy, myeoblasts appeared, and
      the diagnosis of AML was then made. The myeloblasts proliferated in response to G
      CSF in vitro and in vivo. In AA, development of AML after treatment with G-CSF is
      rare. Therefore a careful observation for leukaemic transformation is necessary
      in long-term administration of G-CSF for AA.

PMID- 7527652
TI  - Cytokine response pattern in Sweet's syndrome associated with myelodysplasia.

PMID- 7527653
TI  - A non-radioactive, sensitive method for the detection of DNA fragmentation in
      apoptotic cells (rat pheochromocytoma PC12 and rat cortical cells).
AB  - A new method is described which is suitable for reliably analysing apoptotic
      fragmentation in small amounts of DNA. After isolation, DNA was labelled with
      biotin-4-dUTP using Klenow polymerase. Then DNA was size-separated by agarose gel
      electrophoresis, blot transferred and subsequently visualized by the streptavidin
      alkaline phosphatase-BCIP/NBT procedure. This non-radioactive method was used to
      detect apoptotic DNA in rat pheochromocytoma PC12 cells, treated with tributyltin
      (1 nM). While only 30 ng of DNA is required for analysis of apoptotic DNA using
      the new blot technique, 100-fold more material is needed to identify the
      fragmentation of DNA after separation by agarose gel electrophoresis and direct
      staining with ethidium bromide. In a further set of experiments, rat cortical
      cells were incubated with human immunodeficiency virus type 1 viral glycoprotein
      of M(r) of 120 kDa (gp120) to induce apoptosis. More than 0.3 ng of gp 120/ml are
      required to detect apoptotic DNA by the direct procedure; only 0.1 ng gp120/ml or
      less were sufficient to document clear DNA fragmentation using the non
      radioactive blotting technique described here. These results demonstrate that the
      new procedure can be used to analyse very small amounts of apoptotic DNA and
      shows that gp120-induced apoptosis can be measured at low concentrations of the
      viral protein.

PMID- 7527654
TI  - Phase II trial of edatrexate in patients with advanced hepatocellular carcinoma.
AB  - BACKGROUND: The methotrexate analogue edatrexate (10-ethyl-10-deaza-aminopterin,
      or 10-EDAM) has demonstrated greater activity than methotrexate has against
      murine tumors and human tumor xenografts. Phase II trials of edatrexate have
      already demonstrated its activity against breast, lung, and head and neck
      carcinomas. A phase II trial of edatrexate was conducted in patients with
      advanced hepatocellular carcinoma. PATIENTS AND METHODS: Seventeen patients with
      previously untreated unresectable hepatocellular carcinoma were enrolled on the
      study. Edatrexate, 80 mg/m2 weekly for 5 weeks, was administered intravenously.
      The treatment course was repeated every 6 weeks. Tumor response was evaluated by
      computerized tomographic scan after 2 courses. RESULTS: No complete or partial
      responses were observed in this trial. Two minor responses, each lasting less
      than 12 weeks, were observed. Twelve patients had elevated serum alpha
      fetoprotein (AFP) levels at entry into the study; 4 of the 12 patients
      experienced a > or = 25% decrease in the level of this tumor marker; 3 of the 4
      had a > 50% reduction in AFP level. Grade 3 and 4 toxic effects were
      granulocytopenia, thrombocytopenia, anemia, oral mucositis, skin reactions,
      fatigue, anorexia, and diarrhea. CONCLUSIONS: Edatrexate administered at this
      dose and schedule appears to have little therapeutic efficacy against advanced
      hepatocellular carcinoma.

PMID- 7527655
TI  - Pancreatic exocrine enzymes and intrapancreatic protein synthesis in acute
      oedematous pancreatitis.
AB  - Changes in serum and intrapancreatic enzyme content and protein synthesis in
      pancreas were studied in acute oedematous pancreatitis (AOP). Male Wistar rats (n
      = 111) were divided into 2 groups, controls with a sham operation and those with
      AOP. Serum amylase levels rose immediately after the procedure causing AOP and
      then fell gradually, while serum lipase and ribonuclease levels remained higher
      than control values over 48 h. (p < 0.05, 0.01). Serum deoxyribonuclease (DNase)
      II levels were unchanged. Intrapancreatic enzyme levels were scarcely affected by
      AOP. 3H-leucine uptake into pancreatic tissue of rats with AOP was decreased
      throughout the study (p < 0.001), but some protein synthesis continued.
      Intrapancreatic enzyme contents are maintained despite diffusion into the blood
      because the pancreas retain its ability to synthesize enzymes.

PMID- 7527656
TI  - Characterization of neuronal nitric oxide synthase and a C415H mutant, purified
      from a baculovirus overexpression system.
AB  - Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to citrulline
      and nitric oxide (.NO). A baculovirus overexpression system has been developed
      for a constitutive NOS isoform, cloned originally from rat cerebellum (B-NOS).
      Recombinant virus was used at a multiplicity of infection of 5 to infect
      Spodoptera frugiperda cells in culture, and NOS was expressed to 10% of the total
      soluble protein at 48 h postinfection. In order to express catalytically active
      enzyme, it was necessary to supplement the culture media with hemin. This
      increased the activity of the enzyme 7-fold. A two column affinity purification
      was developed for the recombinant enzyme, which gave homogeneous protein that
      migrated at 150 kDa on a denaturing polyacrylamide gel. A Km for L-arginine was
      determined to be 2.0 +/- 0.4 microM. As isolated, recombinant B-NOS exhibited a
      Soret maximum at 402 nm, which shifted to 394 nm in the presence of L-arginine.
      The Soret maximum of the reduced enzyme in the presence of CO was 444 nm. Initial
      rate steady-state kinetic analysis of the recombinant B-NOS showed evidence of
      substrate inhibition by L-arginine, which could also be seen in a partially
      purified preparation of B-NOS from rat cerebella. This substrate inhibition was
      not observed with the inducible isoform of NOS, purified from immunostimulated
      murine macrophages. A C415H mutant was overexpressed and purified using the same
      conditions established for the wild-type recombinant B-NOS. This C415H mutant
      exhibited no activity and did not bind heme, providing the first experimental
      evidence to support previously reported primary amino acid comparisons which
      suggest that C415 provides the coordinating thiolate to the heme moiety in B-NOS.

PMID- 7527658
TI  - Study by infrared spectroscopy of the interaction of bovine myelin basic protein
      with phosphatidic acid.
AB  - The effect of bovine myelin basic protein (MBP) on dimyristoylphosphatidic acid
      (DMPA) and phosphatidic acid prepared from egg yolk phosphatidylcholine (EPA) has
      been investigated by transmission and attenuated total reflectance (ATR) Fourier
      transform infrared spectroscopy. Interaction of MBP with DMPA and EPA dispersions
      decreases the lipid acyl chain conformational disorder as a consequence of
      hydrophobic interactions of the protein with the lipids. Since these effects are
      more important for EPA dispersions than for DMPA, MBP is believed to penetrate
      more into EPA bilayers. This could be due to the fact that the hydrogen bond
      network formed by the charged polar headgroups of EPA is weaker than that of
      DMPA. This is supported by the spectra of the phosphate region showing that the
      phosphate groups of EPA are less hydrogen bonded than DMPA. In the presence of
      MBP, the hydrogen bond network is replaced by electrostatic interactions of the
      protein with the polar headgroups of the lipid. Infrared spectra of the polar
      headgroup region also show evidence that MBP enhanced the second ionization state
      of the phosphate group at neutral pH, this effect being more important for EPA
      than for DMPA bilayers. Also, infrared spectra of the lipid carbonyl stretching
      region show evidence that MBP limits the accessibility of water molecules to the
      interfacial part of the lipid bilayer. Finally, ATR measurements on oriented
      films of lipid/protein complexes indicate that the penetration of the protein
      into the lipid bilayer is followed by a reorientation of the lipid acyl chains
      toward the normal to the bilayer in the case of EPA.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7527657
TI  - Characterization of the inactivation of nitric oxide synthase by NG-methyl-L
      arginine: evidence for heme loss.
AB  - The nitric oxide synthases (NOS) are a unique family of P450-type hemoproteins
      that catalyze the formation of .NO and citrulline from L-arginine, oxygen, and
      NADPH. NG-Methyl-L-arginine (L-NMA) has been shown to function as a slow,
      partially uncoupled alternate substrate and mechanism-based inhibitor of the
      inducible NOS [Olken, N. M., & Marletta, M. A. (1993) Biochemistry 32, 9677
      9685]. In this report, the inactivation of NOS by L-NMA has been investigated in
      detail. Inactivation fails to occur under an argon atmosphere, establishing
      turnover dependence. The partition ratio, defined as the number of molecules of
      citrulline formed per NOS monomer inactivated, is 108 +/- 3. By utilizing NG
      methyl-L-[2,3-3H2]arginine and NG-[14C]methyl-L-arginine, the stoichiometry of
      radiolabeling is 0.11 +/- 0.01 equiv of tritium and 0.41 +/- 0.10 equiv of carbon
      14 per inactivated NOS monomer. Dialysis under native conditions does not change
      this stoichiometry. However, dialysis of NOS following denaturation decreases the
      stoichiometry of radiolabeling to 0.08 +/- 0.04 equiv of tritium and 0.12 +/-
      0.04 equiv of carbon-14 per inactivated NOS monomer. Absolute and CO-reduced
      difference spectroscopy indicates that inactivation of L-NMA is accompanied by a
      substantial loss of the heme chromophore, which is not prevented by catalase.
      HPLC analysis of NOS heme following inactivation with L-NMA indicates substantial
      loss of heme. These findings suggest that multiple mechanisms may contribute to
      the loss of NOS activity by L-NMA, including heme loss and possibly protein and
      cofactor modification.

PMID- 7527659
TI  - Isolation and characterization of natural protein-associated carbohydrate ligands
      for E-selectin.
AB  - A comparative analysis of carbohydrate 'libraries' derived from cell lines
      binding E-selectin with differing avidity identified endogenous protein
      associated carbohydrate ligand candidates for E-selectin. Three unusual
      structures, which constitute less than 3% of cell surface protein-associated
      carbohydrate, were unique to the E-selectin-binding cells, including neutrophils
      and the monocytic cell line U937. All are tetraantennary N-linked structures with
      a NeuAc alpha 2-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc beta 1-->3Gal beta 1-->4
      (Fuc alpha 1-->3)GlcNAc lactosaminoglycan extension (diSLex) on the arm linked
      through the C4 residue on the mannose. While all contained the expected SLex
      [NeuAc alpha 2-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc] moiety, these structures
      have an additional fucosylated lactosamine unit. Direct evidence that these
      diSLex-containing structures are, indeed, high-affinity ligands for E-selectin
      came from the use of recombinant soluble E-selectin-agarose affinity
      chromatography. We found that these three carbohydrate structures bound
      specifically to the E-selectin column. SLex itself does not bind under identical
      conditions. In summary, these related structures: (1) all possess an unusual 3
      sialyl di-Lewis x extension on one arm of an N-linked tetraantennary glycan; (2)
      of the cells tested, are present only on E-selectin-binding leukocytes and
      leukocytic cell lines; (3) bind to E-selectin with a relatively high affinity (Kd
      < microM) and one greater than that of 3-sialyl Lewis x or 3-sialyl Lewis a; and
      (4) represent a very small percentage of the protein-associated carbohydrate.
      These carbohydrate structures appear to be present on only a very small number of
      cell surface proteins and may alone be responsible for the specificity of E
      selectin-dependent adhesion.

PMID- 7527660
TI  - Catalysis of RNA cleavage by a ribozyme derived from the group I intron of
      Anabaena pre-tRNA(Leu).
AB  - In the cyanobacterium Anabaena PCC7120, the precursor to tRNA(Leu) contains a 249
      nucleotide group I intron that undergoes efficient self-splicing in vitro. By
      deleting the 5' and 3' splice sites, this intron has now been converted to an RNA
      enzyme that uses a guanosine nucleophile to cleave substrate RNAs (S) with
      multiple turnover. This Anabaena ribozyme has a second-order rate constant for
      RNA cleavage (kcat/Km)S that is 250-500-fold smaller than that of the Tetrahymena
      ribozyme, and a multiple-turnover rate constant at saturating S [kcat(mt)] that
      is approximately 400-fold larger. Several lines of evidence, including kinetic
      analysis of cleavage of phosphorothioate- and deoxynucleotide-substituted
      substrates and pH dependence, support the conclusion that both (kcat/Km)S and
      kcat(mt) are limited by the actual chemical cleavage step. In contrast, for the
      Tetrahymena ribozyme, it has been shown that neither of these rate constants
      reflects the chemical step. These kinetic differences are expected from the
      shorter guide sequence-substrate pairing of the Anabaena ribozyme; for example,
      weaker binding of RNA speeds product release during multiple turnover and thereby
      overcomes the rate-limiting product release observed for the Tetrahymena
      ribozyme. Thus, the large kinetic differences represent superficial rather than
      fundamental differences between these ribozymes. Furthermore, the strength of the
      guanosine-binding interaction, the stereospecificity for Rp-phosphorothioate at
      the cleavage site, and the 10(3)-fold slower cleavage with a deoxyribonucleoside
      leaving group are properties conserved between the Anabaena and Tetrahymena
      ribozymes. Finally, log(kcat/Km)S increases linearly with pH in the acid range
      where chemistry is rate-limiting and becomes pH-independent above pH 7, perhaps
      because a conformational step becomes rate-limiting; again, these are
      characteristics shared with the Tetrahymena ribozyme. We conclude that two group
      I ribozymes, although differing in the identity of many of their active site
      nucleotides, nevertheless provide functionally similar active sites for sequence
      specific RNA cleavage.

PMID- 7527661
TI  - Neural cell-adhesion molecule (CD 56)-positive, t(8;21) acute myeloid leukemia
      (AML, M-2) and granulocytic sarcoma.
AB  - A 49-year-old man with t(8; 21) acute myeloid leukemia relapsed 8 months after
      successful induction chemotherapy with a paraspinal granulocytic sarcoma. There
      was no evidence of leukemia in the bone marrow at relapse. At initial
      presentation, the blasts co-expressed CD 15, CD 33, CD 34, CD 45, CD 19, and CD
      56 (a neural cell-adhesion molecule). Expression of certain cell-adhesion
      molecules on leukemic blasts may determine a tendency to develop extramedullary
      relapse. The co-expression of CD 56 may have a role in the predisposition of t(8;
      21) AML to develop GS.

PMID- 7527664
TI  - In vitro megakaryocytopoietic and thrombopoietic activity of c-mpl ligand (TPO)
      on purified murine hematopoietic stem cells.
AB  - Recently, the ligand for c-mpl has been identified and cloned. Initial studies of
      this molecule indicate that it is the platelet regulatory factor, thrombopoietin
      (TPO). Previous work has indicated that c-mpl is expressed in very immature
      hematopoietic precursors and thus raised the possibility that TPO may act
      directly on the hematopoietic stem cell. Therefore, in these studies, we
      investigate the effects of TPO on hematopoietic stem cell populations isolated
      from the murine fetal liver and bone marrow. Cocultivation of stem cells with
      fetal liver stroma give rise to multilineage expansion of the stem cells but with
      little or no megakaryocytopoiesis. Addition of TPO to these cocultures gives
      significant megakaryocyte production. This production is enhanced in combination
      with Kit ligand or interleukin-3. The addition of TPO to stem cell suspension
      cultures produces a dynamic thrombopoietic system in which stem cells undergo
      differentiation to produce megakaryocytes and proplatelets. These experiments
      show that the megakaryocytopoietic and thrombopoietic activities of TPO are
      initiated at the level of an early progenitor cell or upon the hematopoietic stem
      cell.

PMID- 7527663
TI  - Epidemiology of hepatitis C virus infection in patients with renal disease.
AB  - This study was carried out to determine the prevalence of hepatitis C virus (HCV)
      antibodies and the epidemiologic factors associated with HCV infection in
      patients with chronic renal failure before the onset of ESRD. Sex, age, type of
      renal disease, level of renal function, and history of blood transfusions and
      invasive procedures were analyzed in 226 patients with renal disease, compared
      with a population of 1,244 normal subjects and 124 patients with impaired
      immunity (patients having autoimmune diseases and receiving chemotherapy
      treatment). Eighteen seropositive patients with renal disease (prevalence, 7.9%)
      were found, which was significantly higher than the prevalence in the normal
      population (1.03% in blood donors, 0.98% in pregnant women; P < 0.001, chi 2).
      There was no significant association of sex, number of blood transfusions, or
      history of invasive procedures with the presence of HCV antibodies. The
      prevalence of HCV antibodies was higher (16.6%) in patients with
      glomerulonephritis compared with patients diagnosed with interstitial nephritis,
      pyelonephritis, nephrosclerosis, diabetes mellitus, polycystic kidney, and
      miscellaneous renal diseases (P < 0.01, chi 2). There was a higher prevalence of
      HCV antibodies in patients with creatinine clearance lower than 30 mL/min (13%)
      compared with patients with creatinine clearance higher than 30 mL/min (2.7%) (P
      < 0.01, chi 2). These data suggest that HCV infection may be associated with the
      pathogenesis of glomerulonephritis. Alternatively, glomerulonephritis or severe
      renal insufficiency may increase the likelihood of HCV infection.

PMID- 7527662
TI  - Effective stimulation of neutropoiesis with rh G-CSF in dyskeratosis congenita: a
      case report.
AB  - Dyskeratosis congenita (DC) is a rare congenital X-linked disorder. The major
      clinical manifestations are abnormal skin pigmentation, nail dystrophy, and
      leukoplakia of mucosal membranes. About 50% of the patients develop bone marrow
      failure, which is partly responsible for the poor prognosis. Recombinant human
      granulocyte-macrophage colony-stimulating factor (rhGM-CSF) has been administered
      to some neutropenic patients with DC, but only a moderate stimulation of
      neutropoiesis has been observed. We report on a patient with DC treated with
      recombinant human granulocyte-colony-stimulating factor (rhG-CSF). This treatment
      resulted in a substantial dose-dependent increase in the neutrophil count.

PMID- 7527665
TI  - Synergistic actions of stem cell factor and other burst-promoting activities on
      proliferation of CD34+ highly purified blood progenitors expressing HLA-DR or
      different levels of c-kit protein.
AB  - We studied the synergistic effects of stem cell factor (SCF) and other burst
      promoting activities (BPAs) such as interleukin-3 (IL-3), granulocyte-macrophage
      colony-stimulating factor (GM-CSF), or IL-9 on proliferation of human peripheral
      blood-derived highly purified progenitors. SCF, IL-3, GM-CSF, and IL-9 showed
      significant BPA when CD34+HLA-DR+ cells were used as the target population. IL-3
      exerted the most potent BPA, and GM-CSF supported approximately 40% to 70% of the
      erythroid burst-forming units that are responsive to IL-3. SCF and IL-9 showed
      much weaker BPA than that of IL-3 or GM-CSF. Combinations of IL-3 with other BPAs
      did not show synergistic actions supporting erythroid-burst formation. However,
      GM-CSF showed a significant additive effect with IL-9 or SCF. When CD34+c-kithigh
      cells were used as the target, SCF showed a much stronger BPA. Also, a distinct
      additive effect between SCF and IL-3 or GM-CSF on erythrocyte-containing mixed
      colony formation was observed. On the other hand, when CD34+c-kitlow cells were
      used as the target, SCF, IL-3, and GM-CSF could express BPA. In contrast, IL-9
      alone failed to support erythroid-burst formation. Because CD34+c-kithigh cells
      weakly expressed CD34 antigen, these cells appeared to be more mature progenitors
      than CD34+c-kitlow cells. These results suggest that IL-9 acts on more mature
      progenitors than those of SCF, IL-3, or GM-CSF and that the primary target of SCF
      is multipotential progenitors at the very early stage of development.

PMID- 7527666
TI  - Hydrocortisone differentially affects the ability of murine stromal cells and
      human marrow-derived adherent cells to promote the differentiation of CD34++/CD38
      long-term culture-initiating cells.
AB  - Very primitive human hematopoietic progenitor cells are identified indirectly by
      their ability to give rise to clonogenic progenitors in the presence of either
      human or murine stromal cells. These long-term culture-initiating cell (LTC-IC)
      assays are usually performed in the presence of hydrocortisone based on the
      initial observation that hydrocortisone was required for prolonged hematopoiesis
      in standard long-term bone marrow cultures. In this report, we investigated the
      role of hydrocortisone in LTC-IC assays initiated with CD34++/CD38- cells seeded
      onto either human bone marrow LTC-derived adherent cells or a murine marrow
      derived stromal cell line, MS-5. It was found that weekly addition of
      hydrocortisone to the cultures reduced the frequency of LTC-IC (from 1/5 to 1/20)
      calculated from limiting dilution experiments and also reduced fivefold to 10
      fold the number of their progeny clonogenic cells detected after 4 to 5 weeks. In
      contrast, the frequency and differentiative potential of CD34++/CD38- grown in
      the presence of human marrow feeders was unaltered by the addition of
      glucocorticoids. Data are consistent with the hypothesis that hydrocortisone
      inhibited LTC-IC differentiation by downregulating the expression of a
      synergistic factor produced by MS-5 cells. (1) In the absence of hydrocortisone,
      the number of clonogenic progenitors generated by LTC-IC was much higher in
      cultures seeded on MS-5 than in cultures seeded on human marrow adherent cells,
      which was also true when cytokines were added to the cocultures. However, based
      on the phenotype of the colonies, progenitors produced in MS-5 cocultures were
      more mature than those generated on human marrow adherent cells. (2)
      Hydrocortisone counteracted the stimulatory effect of recombinant human cytokines
      (interleukin-3, interleukin-6, and steel factor) in assays performed on MS-5 but
      not on human marrow feeders. (3) Hydrocortisone led to a 50% decrease in the
      numbers of colony-forming units-granulocyte-macrophage found in methycellulose
      colony assays of CD34++/CD38- cells performed in the presence of MS-5 cells.
      Taken together, our results indicate that hydrocortisone acts differently on a
      murine stromal cell line and on marrow-derived human stromal cells and may
      suppress the expression by MS-5 cells of an activity selectively promoting
      amplification of clonogenic cells derived from primitive LTC-IC.

PMID- 7527667
TI  - Regulation of interleukin-11 protein and mRNA expression in neonatal and adult
      fibroblasts and endothelial cells.
AB  - Interleukin-11 (IL-11), a newly-identified cytokine produced by stromal cells,
      elevates platelet counts in neonatal rats in vivo and synergizes in vitro with IL
      3 in supporting murine megakaryocyte colony formation and stimulating
      hematopoietic stem cells. Megakaryocytopoiesis is also enhanced by other colony
      stimulating factors (CSFs), including IL-3, IL-6, and Steel factor (SLF).
      Dysregulation of neonatal thrombopoiesis predisposes newborns to develop
      thrombocytopenia during sepsis, despite increased circulating pools of committed
      thrombopoietic progenitors in newborn cord blood compared with adult. We
      previously reported reduced expression of granulocyte-macrophage colony
      stimulating factor (GM-CSF), granulocyte-colony-stimulating factor (G-CSF), and
      IL-3 from stimulated cord mononuclear cells, but increased expression of SLF in
      human umbilical vein endothelial cells (HUVEC). Therefore, we hypothesized that
      IL-3, IL-6, and SLF might modulate megakaryocytopoiesis by inducing IL-11
      expression, and newborns might express altered levels of IL-11 mRNA expression
      during activated conditions, contributing to the difference in circulating colony
      forming unit-megakaryocyte (CFU-Meg) cord and adult blood. Phorbol myristate
      acetate (PMA) induced a twofold greater increase in IL-11 mRNA expression in
      neonatal fibroblasts (NFb) compared with adult fibroblasts (AFb), and a 3.6-fold
      greater increase in HUVEC than human adult aorta endothelial cells (HAEC) by
      Northern blot analysis. PMA also induced a threefold greater increase in IL-11
      protein production in NFb than AFb. Physiologic agonists IL-1 alpha, transforming
      growth factor-beta 1 (TGF-beta 1), and TGF-beta 2 triggered upregulation of IL-11
      mRNA expression in both NFb and AFb. However, IL-3, IL-6, PIXY321 (a GM-CSF-IL-3
      fusion protein), and SLF failed to upregulate IL-11 mRNA expression from the
      basal level, while macrophage-colony stimulating factor (M-CSF) mRNA was
      significantly induced. These data suggest that the hematopoietic effect of IL-6,
      SLF, and IL-3 on megakaryocytopoiesis is probably not mediated by secondary IL-11
      mRNA expression. Similarly, inflammatory agonists IL-1 beta, lipopolysaccharide
      (LPS), and tumor necrosis factor-alpha (TNF-alpha) alone did not upregulate IL-11
      expression from the basal level in endothelial cells, whereas intracellular
      adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 were
      strongly induced. Minimal basal IL-11 expression was detected by reverse
      transcriptase-polymerase chain reaction (RT-PCR) in NFb, AFb, HUVEC and HAEC. The
      quantitative RT-PCR assay also verified that IL-1 beta and TNF-alpha-stimulated
      HUVEC and HAEC, and IL-3- and IL-6-stimulated NFb and AFb only expressed minimal
      levels of IL-11 mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7527668
TI  - Induction of tyrosine phosphorylation of Vav and expression of Pim-1 correlates
      with Jak2-mediated growth signaling from the erythropoietin receptor.
AB  - The receptor for erythropoietin (Epo) belongs to the cytokine receptor family and
      lacks a tyrosine kinase domain. However, it has been hypothesized that a tyrosine
      kinase, Jak2, associates with the membrane proximal cytoplasmic region of Epo
      receptor (EpoR) and mediates the growth signaling from the receptor through
      tyrosine phosphorylation of cellular substrates. To explore the growth signaling
      pathways from the EpoR, we analyzed substrates of tyrosine phosphorylation
      induced by Epo stimulation in cells expressing various mutant EpoRs. The vav
      proto-oncogene product was found to be tyrosine phosphorylated after Epo
      stimulation in cells expressing the wild-type EpoR or a truncated receptor, H
      mutant, that retains the growth signaling function. In these cells, Epo also
      induced the expression of a serine/threonine kinase, Pim-1. However, Epo
      stimulation did not have any effect on Vav or Pim-1 in cells expressing a mutant
      EpoR, PM4 mutant, inactivated by a point mutation, Trp282 to Arg, in the membrane
      proximal region, which abrogates the interaction with Jak2. On the other hand,
      both tyrosine phosphorylation of Vav and expression of Pim-1 were observed
      constitutively in cells expressing a mutant EpoR that is constitutively activated
      by a point mutation, Arg 129 to Cys, in the extracellular domain. Jak2 was also
      constitutively tyrosine phosphorylated and activated in cells expressing this
      mutant, which confirms the crucial role of Jak2 in growth signaling from the
      EpoR. Taken together, these observations suggest that the tyrosine
      phosphorylation of Vav and the expression of Pim-1 may play important roles in
      growth signaling from the EpoR.

PMID- 7527669
TI  - Cytokine production by primary bone marrow megakaryocytes.
AB  - Primary human bone marrow megakaryocytes were studied for their ability to
      express and release cytokines potentially relevant to their proliferation and/or
      differentiation. The purity of the bone marrow megakaryocytes was assessed by
      morphologic and immunocytochemical criteria. Unstimulated marrow megakaryocytes
      constitutively expressed genes for interleukin-1 beta (IL-1 beta), IL-6,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis
      factor-alpha (TNF-alpha), by the polymerase chain reaction (PCR) and Northern
      blot analysis. At the protein level, megakaryocytes secreted significant amounts
      of IL-1 beta (53.6 +/- 3.6 pg/mL), IL-6 (57.6 +/- 15.6 pg/mL), and GM-CSF (24 +/-
      4 pg/mL) but not TNF-alpha. Exposure of human marrow megakaryocytes to IL-1 beta
      increased the levels of IL-6 (87.3 +/- 2.3 pg/mL) detected in the culture
      supernatants. Transforming growth factor-beta was also able to stimulate IL-6, IL
      1 beta, and GM-CSF secretion, but was less potent than stimulation with phorbol
      12-myristate-13-acetate (PMA). The secreted cytokines acted additively to
      maintain and increase the number of colony-forming unit-megakaryocytes colonies
      (approximately 35%). These studies demonstrate the production of multiple
      cytokines by isolated human bone marrow megakaryocytes constitutively or
      stimulated in vitro. The capacity of human megakaryocytes to synthesize several
      cytokines known to modulate hematopoietic cells supports the concept that there
      may be an autocrine mechanism operative in the regulation of
      megakaryocytopoiesis.

PMID- 7527670
TI  - Mutual inhibition of murine erythropoiesis and granulopoiesis during combined
      erythropoietin, granulocyte colony-stimulating factor, and stem cell factor
      administration: in vivo interactions and dose-response surfaces.
AB  - We investigated the in vivo effects of erythropoietin (EPO) on granulopoiesis
      and, conversely, the effect of granulocyte colony-stimulating factor (G-CSF)
      treatment on erythropoiesis. Recombinant human EPO at four different doses in
      combination with recombinant human G-CSF also at four different doses was
      simultaneously administered for 7 days to splenectomized mice. In total, 16
      different combinations of growth factors were thus tested. G-CSF administration
      increased granulocyte production as expected, whereas immature colony-forming
      unit granulocyte-macrophage numbers were decreased. EPO analogously increased
      late erythroid cell numbers. Both EPO and G-CSF dose-dependently inhibited late
      cell stages of the opposite lineage, with EPO abrogating G-CSF-stimulated
      granulopoiesis and, conversely, G-CSF inhibiting EPO-stimulated erythropoiesis.
      In a subsequent experiment, we tested whether these lineage-competitive effects
      could be prevented by coadministering stem cell factor (SCF). In these three
      factor-treated mice, all granuloid and erythroid cell stages increased, thereby
      reducing the effect of the mutual inhibition. We conclude that EPO-stimulated
      erythropoiesis and G-CSF-stimulated granulopoiesis inhibited each other at a late
      level. Simultaneous SCF administration increased the input into both the
      erythroid and granuloid compartment and thereby compensated the mutual
      inhibition. This study shows that intricate dose-response relationships exist
      between various growth factors that should be carefully analyzed before
      combinations of these factors are used in humans.

PMID- 7527671
TI  - YC-1, a novel activator of platelet guanylate cyclase.
AB  - YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] inhibited the aggregation
      of and ATP release from washed rabbit platelets induced by arachidonic acid (AA),
      collagen, U46619, platelet-activating factor (PAF), and thrombin in a
      concentration-dependent manner. YC-1 also disaggregated the clumped platelets
      caused by these inducers. The thromboxane B2 formation caused by collagen, PAF,
      and thrombin was inhibited by concentrations of YC-1 that did not affect
      formation of thromboxane B2 and prostaglandin D2 caused by AA. YC-1 suppressed
      the increase of intracellular Ca2+ concentration and generation of inositol 1,4,5
      trisphosphate caused by these five aggregation inducers. Both the cAMP and cGMP
      contents of platelets were increased by YC-1 in a concentration- and time
      dependent manner. Like sodium nitroprusside, YC-1 potentiated formation of cAMP
      caused by prostaglandin E1 but not that by 3-isobutyl-1-methylxanthine. Adenylate
      cyclase and cAMP phosphodiesterase activities were not altered by YC-1. Activity
      of cGMP phosphodiesterase was unaffected by YC-1. Activities of guanylate cyclase
      in platelet homogenate and cytosolic fraction were activated by YC-1, whereas
      particulate guanylate cyclase activity was unaffected. The antiplatelet effect of
      sodium nitroprusside but not that of YC-1 was blocked by hemoglobin and
      potentiated by superoxide dismutase. After intraperitoneal administration for 30
      minutes, YC-1 prolonged the tail bleeding time of conscious mice. These data
      indicate that YC-1 is a direct soluble guanylate cyclase activator in rabbit
      platelets. It may also possess antithrombotic potential in vivo.

PMID- 7527672
TI  - Kit ligand/mast cell growth factor-independent differentiation of mast cells in
      myelodysplasia and chronic myeloid leukemic blast crisis.
AB  - Autonomous, factor-independent growth and differentiation of malignant cells in
      preleukemic and leukemic disease states is a well-recognized phenomenon and is
      often associated with a poor prognosis. Mast cells are distinct hematopoietic
      cells and express a unique profile of antigens. Growth and differentiation of
      normal mast cells is dependent on mast cell growth factor (MGF), the ligand of
      the c-kit protooncogene product. In this study, we screened for mast cell-lineage
      involvement in 52 patients suffering from myeloid leukemias, myelodysplastic
      syndromes (MDS), systemic mastocytosis, or other diseases by probing for mast
      cell-related molecules (c-kit, tryptase, histamine, and MGF) and by analyzing kit
      ligand/MGF-independent growth of mast cells in long-term suspension culture. Of
      the 52 patients tested, 2 patients with refractory anemia with excess of blast
      cells in transformation and 1 patient suffering from chronic myeloid leukemia
      blast crisis (CML-BC) were diagnosed as mastocytic disease. These patients were
      characterized by complex chromosomal abnormalities, splenomegaly, high
      percentages of circulating metachromatic cells (5% to 25%), high levels of
      cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a
      tryptase/histamine (ng:ng) ratio greater than 1. The metachromatic cells
      expressed the mast-cell-related surface antigen c-kit, but not basophil-related
      antigens (CD11b, CDw17). Furthermore, in these 3 patients, spontaneous, MGF
      independent growth of mast cells along with spontaneous synthesis of tryptase was
      demonstrable in long-term culture. No autocrine production, paracrine production,
      or overproduction of MGF was found. The spontaneous growth of mast cells could
      neither be abbrogated by addition of monoclonal antibodies (MoAbs) to c-kit nor
      by MoAbs against MGF (< 5% inhibition), whereas factor (MGF)-dependent
      differentiation of mast cells in these patients could be abbrogated by MoAbs to c
      kit or MoAbs to MGF (> 70% inhibition, P < .001). In addition, serum MGF levels
      in these patients were within the normal range and MGF could not be detected in
      cell-free culture supernatants. All 3 patients showed rapid progression of
      disease and had a survival time of less than 1 year. In conclusion, we describe a
      unique form of transformation in MDS and CML-BC characterized by mast cell
      lineage involvement and factor-independent differentiation of mast cells. This
      form of leukemic transformation has to be delineated from chronic myeloid
      leukemia with basophilia or basophil crisis, from primary mast cell leukemia, and
      from monocytic leukemias and myelodysplastic disorders associated with
      basophilia.

PMID- 7527673
TI  - alpha-Amino butyric acid cannot reactivate the silenced gamma gene of the beta
      locus YAC transgenic mouse.
AB  - Butyric acid, a naturally occurring fatty acid, has been shown to increase fetal
      hemoglobin in BFUe cultures, in primates, and in patients with beta chain
      hemoglobinopathies. The precise mechanism of gamma gene induction by butyrate is
      unknown. Butyrate may induce fetal hemoglobin production in vivo by reactivation
      of silenced gamma globin genes, by inhibiting the silencing of gamma genes, or by
      both mechanisms. We examined the effects of butyrate on gamma gene expression in
      transgenic mice carrying three types of constructs: microLCRA gamma mice, which
      continue to express the gamma gene in the adult stage of development at a level
      of one-third to one-fifth of the expression in the fetus; microLCRA gamma psi
      beta delta beta mice, which display correct developmental regulation of gamma and
      beta human globin genes and have low level gamma globin expression in the adult;
      and beta locus YAC mice, which display correct developmental regulation of
      epsilon, gamma, and beta globin genes and have a totally silenced gamma gene in
      the adult stage. Animals were treated with a continuous infusion of alpha-amino
      butyric acid (alpha-ABA) for 7 days. In microLCRA gamma mice alpha-ABA produced
      up to a 43-fold induction of gamma and 9-fold induction of mouse alpha globin
      genes. In contrast, butyrate did not induce gamma globin expression in the beta
      locus YAC mice. However, the gamma globin genes of beta locus YAC mice were
      activated after administration of 5-azacytidine (5-azaC), and the level of gamma
      globin expression was further increased by administration of alpha-ABA. These
      results suggest that butyrate cannot reactivate a totally silenced gamma gene and
      that induction of fetal hemoglobin by this compound may require the presence of
      preactivated gamma globin genes.

PMID- 7527676
TI  - Stem cell factor and the amplification of progenitor cells from CD34+ cord blood
      cells.
AB  - We have studied the frequency of colony-forming cells (CFC) in fetal and neonatal
      blood in comparison with adult blood and marrow. Fetal or neonatal blood contains
      at least as many CFC as adult marrow and higher numbers of the more primitive CFC
      -those CFC (mixed-cell CFC) giving rise to colonies composed of erythroid and
      myeloid cells. CD34+ cord blood cells (selected by one of several means)
      proliferate in culture over time and generate more CFC (from pre-CFC) and
      differentiated cells in response to stem cell factor (SCF) plus different
      hematopoietic growth factors. For its effect, SCF requires the synergistic action
      of erythropoietin (Epo), granulocyte colony-stimulating factor (G-CSF), or
      interleukin-3 (IL-3). In the presence of Epo or G-CSF, CFC and differentiated
      cells are generated for 15 days and are mainly erythroid or granulocytic,
      respectively. In contrast, SCF plus IL-3 generate multilineage CFC and
      differentiated cells for more than 1 month. When the conditions for these long
      term suspension cultures were optimized, CFC and differentiated cells were
      generated for more than 2 months. At this time, CFC were no longer detectable,
      but cells continued to be generated, and the cells had a mast cell phenotype.
      These cells have been maintained and propagated for more than 8 months in the
      presence of IL-3 and SCF and may represent a useful tool to study human mast cell
      differentiation.

PMID- 7527678
TI  - Adhesion molecules in hematopoietic cells.
AB  - Interaction with stromal cells is known to be crucial for growth and
      differentiation of hematopoietic cells. To characterize adhesion molecules
      involved in this interaction, we examined adhesion of a panel of lymphoid,
      myeloid, and mast cell lines with stromal cells. We found that very late antigen
      4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) were major adhesion
      molecules in lymphoid and myeloid cells, whereas myeloma cells adhered to stromal
      cells through hyaluronate. We investigated regulation of VLA-4 during
      differentiation of myeloid cells using a neutrophil precursor cell line, L-G3.
      Differentiation of neutrophils induced by granulocyte colony-stimulating factor
      was accompanied with down-regulation of VLA-4. Induced L-G3 cells adhered to
      stromal cells in proportion to the expression of VLA-4. Mast cells used two
      mechanisms to adhere to fibroblasts and stromal cells. They adhered to
      fibronectin through VLA-5 when stimulated with steel factor and also directly to
      membrane-anchored steel factor through c-kit.

PMID- 7527677
TI  - Isolation of human hematopoietic stem cells.
AB  - Human hematopoietic stem cells are contained within a population of marrow cells
      that expresses the CD34 antigen but not other antigens associated with commitment
      to specific lineages. Evidence that stem cells capable of maintaining long-term
      hematopoiesis are within this CD34+ lineage-negative (Lin-) population is
      reviewed, including in vivo studies in humans and nonhuman primates. In vitro
      studies of the CD34+ Lin- population have indicated that the blast-sized cells,
      which are presumably in cycle, proliferate and give rise to colony-forming cells
      in the presence of combinations of growth factors, including c-kit ligand and
      interleukin-3 (IL-3). Recent studies have examined the factors required for the
      growth of the quiescent subset of the CD34+ Lin- cells, identified as small to
      medium lymphocyte-sized cells that resist treatment with 4
      hydroperoxycyclophosphamide, a known characteristic of the marrow-repopulating
      cell. These studies have shown that an interaction with marrow stromal cells is
      required, in addition to c-kit ligand and IL-3, to induce these cells to
      proliferate and form multiple colony-forming cells. These studies have further
      indicated that this effect of stroma is mediated by a soluble factor(s). This
      activity may represent a novel factor(s) and/or a novel combination of growth
      factors.

PMID- 7527675
TI  - Biological properties of subpopulations of pluripotent hematopoietic stem cells
      enriched by elutriation and flow cytometry.
AB  - We have studied several features of pluripotent hematopoietic stem cells (PHSCs)
      and day-12 spleen colony-forming units (CFU-S) obtained from adult murine bone
      marrow. Single-cell suspensions of C57BL/6J mouse bone marrow were fractionated
      by counterflow centrifugal elutriation at flow rates (FR) of 15, 25, 30, and 35
      ml/min, and with the rotor off (R/O). The fractions FR25 and FR35 contained
      approximately equal numbers of PHSC that could repopulate W/Wv mice. These PHSCs
      were further enriched by subtracting lineage-positive cells using monoclonal
      antibodies (MAb) and magnetic immunobeads. The resulting lineage-negative cells
      (Lin-) were then stained with a MAb for the c-kit receptor and sorted by flow
      cytometry. Both subsets were fractionated into cells expressing high (bright) (c
      kitBR), low (dull) c-kitDULL and no (negative, c-kitNEG) c-kit receptor. As few
      as 100 to 200 c-kitBR cells could repopulate the entire thymus and bone marrow in
      W/Wv mice. No PHSCs were present in the c-kitDULL and c-kitNEG fractions. We
      assayed fresh bone marrow and elutriation fractions FR25 and FR35 for gene
      expression by reverse transcriptase polymerase chain reaction. Using a
      semiquantitative protocol, we detected mRNA for beta-globin and flk-2, a protein
      tyrosine kinase receptor, in all samples except the FR25 Lin- c-kitBR subset. We
      consider the cells in FR25 Lin- c-kitBR to be the most primitive set of
      hematopoietic stem cells.

PMID- 7527674
TI  - Marrow transplantation for patients in accelerated phase of chronic myeloid
      leukemia.
AB  - The records were reviewed of 58 patients receiving transplants in Seattle with
      unmanipulated marrow from HLA-identical siblings during the accelerated phase
      (AP) of chronic myeloid leukemia. Variables examined for association with
      survival and relapse included the interval from diagnosis to transplant, the
      reasons for categorization as AP, age, regimen, and cytomegalovirus serology.
      Four patients relapsed. The 4-year probabilities of survival, relapse-free
      survival, nonrelapse mortality, and relapse were 0.49, 0.43, 0.51, and 0.12,
      respectively. After completion of the stepwise multivariate analysis, age less
      than 38 years and categorization as AP solely on the basis of chromosomal
      abnormalities emerged as being independently significantly associated with
      improved survival. The 4-year probability of survival for the 16 patients
      categorized as AP because of chromosomal abnormalities and receiving transplant
      less than 1 year from diagnosis was 0.74. The low probability of relapse in these
      patients suggests that more aggressive preparative regimens are not indicated for
      patients receiving transplants in AP because of the increased risk of transplant
      related mortality.

PMID- 7527681
TI  - Linking key functions and important aspects of care: perspectives on
      perioperative, medical-surgical, and perinatal nursing.
AB  - Most professions are defined, at least in part, by the functions they perform.
      Nursing, it its pursuit of a definition, has begun to define its scientific
      functional base. This article attempts to advance that definition by outlining
      generic functions that define the practice of nursing. The study described in the
      article used these generic functions to determine what quality professionals
      perceived to be the key functions in medical-surgical, perioperative, and
      perinatal nursing. Once defined, these key functions can serve as the basis for
      specialty discipline standards development, research, indicator development, and
      competency definition, assessment, and improvement.

PMID- 7527680
TI  - Pain as a quality management initiative.
AB  - A 320-bed surgical nursing department's pain management quality improvement
      initiative is presented. Clinical indicators were designed through literature
      review and consultation with pain management experts. Results for pain assessment
      compliance, patient perception of relief, and the perceived impact of pain on
      activity--analyzed by nursing care unit, physician service, and pain medication
      type--are detailed, as are selected strategies to improve pain management
      outcomes.

PMID- 7527682
TI  - Control of somitic expression of tenascin in Xenopus embryos by myogenic factors
      and Brachyury.
AB  - Tenascin is a large glycoprotein which is expressed in a restricted pattern in
      the extracellular matrix (ECM) of vertebrate embryos. Tenascin interferes with
      cell-fibronectin interactions in vitro, and may play a role in the control of
      cell migration and differentiation during development. In Xenopus, tenascin
      immunoreactivity is first detected at the early tailbud stage in the ECM of the
      most anterior somite. Thereafter, it is distributed dorsally along neural crest
      cell migration pathways. In this paper, we report that tenascin mRNA is most
      abundant in dorsal mesoderm at the neurula stage and in somites at the early
      tailbud stage, indicating that the initial accumulation of tenascin in the ECM is
      due to secretion from paraxial mesoderm. To understand how tenascin expression in
      somitic mesoderm is controlled, we have expressed Xbra and the myogenic factors
      XMyoD and XMyf5 in blastula animal cap tissue. The tenascin gene is activated by
      all three transcription factors. Interestingly, expression of tenascin mRNA, and
      accumulation of the protein in the ECM, can occur without formation of muscle.
      Our results suggest that tenascin regionalization in early Xenopus embryos
      depends on tenascin RNA expression by somitic mesoderm, where it is likely to be
      activated by myogenic factors.

PMID- 7527684
TI  - Sex differences in acute swim stress induced changes in the binding of AMPA
      (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and kainate to
      glutamate receptors in mouse forebrain.
AB  - Sex differences were found in the binding of [3H]AMPA and [3H]kainate to
      glutamate receptors in synaptosomal membranes prepared from mouse forebrain. The
      number of low affinity [3H]AMPA binding and the affinity of [3H]kainate binding
      was higher in membranes prepared from male mice than from females. Acute swim
      stress (3 min at 32 degrees C) decreased the number of low affinity [3H]AMPA
      binding sites and the affinity of [3H]kainate binding in membranes prepared from
      male mouse forebrain, but not in those prepared from female mice forebrain. As
      kainate is known to interact with low affinity AMPA binding sites, these observed
      changes may be associated with binding sites common to AMPA and kainate. They may
      represent a functional down-regulation of AMPA/kainate binding sites. These sex
      differences in binding to non-NMDA subclasses of glutamate receptors are similar
      to than those found in the binding of MK-801 to the NMDA subclass of glutamate
      receptors, in that the effects of acute swim stress were more pronounced in
      membranes prepared from male than from female mice. The number of low affinity
      [3H]AMPA binding sites were decreased by acute swim stress in membranes from male
      mice, whereas the number of low affinity [3H]MK-801 binding sites increased
      following acute swim stress.

PMID- 7527685
TI  - Combination of interleukin-2-stimulated lymphocytes and bispecific antibodies
      that efficiently lyse leukemic cells does not affect bone marrow CD34-positive
      stem cell function in vitro.
AB  - We have recently reported that a combination of lymphokine-activated killer (LAK)
      cells and bispecific antibodies (BsAb) efficiently lysed autologous and
      allogeneic leukemic blasts that had surface antigens reactive with the BsAb. The
      effector cells used in that experiment were peripheral blood mononuclear cells
      stimulated with interleukin-2 (IL-2) for 2 weeks, with the initial addition of
      anti-CD3 moAb; these were termed T3-LAK effector cells. In this study, we
      examined the effects of T3-LAK cells and BsAb on autologous normal CD34+ BM cells
      in both cytotoxicity and colony formation assays. When T3-LAK cells were
      incubated with CD34+ BM cells, low levels of cytotoxicity were induced against
      the CD34+ BM cells and the cytotoxicity was enhanced by the addition of anti-CD3
      Fab' x anti-CD 13 Fab' BsAb but not by the addition of anti-CD3 Fab' x anti-CD10
      Fab' BsAb. This enhancement appeared to be due to the lysis of CD34+CD13+ BM
      cells. When T3-LAK cells were preincubated with CD34+ BM cells in the presence or
      absence of the BsAb and plated for colony assay, neither the T3-LAK cells nor the
      BsAb affected granulocyte-macrophage or mixed-cell colony formation by CD34+ BM
      cells. Taken together with our previous finding that T3-LAK cells used in
      combination with the BsAb markedly inhibited colony formation by leukemic
      progenitor cells, these results indicate that this combination provides a
      potential new strategy for CD34+ BM cell purging in autologous BMT.

PMID- 7527686
TI  - CD34+ progenitor cell isolation from blood and marrow: a comparison of techniques
      for small-scale selection.
AB  - The isolation and characterization of primitive hematopoietic cells and their
      purification in sufficient numbers is important in clinical and research marrow
      transplantation settings. As systems for large-scale isolation and amplification
      of such cells are developed, they may assume importance in transplantation,
      treatment of marrow failure and for gene therapy applications. Such cells have
      been isolated by numerous techniques and in this work, small-scale isolation of
      CD34+ cells by two immunoadsorption purification methods is compared with
      isolation by flow cytometry. While the immunoadsorption techniques allow for the
      processing of large numbers of density gradient-separated or unseparated cells
      for progenitor isolation, such techniques do not achieve the purity afforded by
      fluorescence activated cell sorter separation.

PMID- 7527683
TI  - Immediate postoperative recovery: measurement and care.
AB  - When considering the postoperative care of surgical patients, there are three
      time periods that are important for both the patient's wellbeing and the planning
      of nursing care. These are termed the immediate recovery period, the intermediate
      stage of dependency, and the more long-term process of returning to normality.
      This article concentrates on the first of these stages.

PMID- 7527679
TI  - Analysis of bone marrow stem cell.
AB  - In this study we define hematopoietic stem cells (HSCs) as a population of cells
      that, when sorted as single cells, gives rise to both myeloid as well as lymphoid
      progeny. We sorted single cells from four populations of CD34+ cells from fetal
      bone marrow: (1) CD38- HLA-DR-, (2) CD38- HLA-DR+, (3) CD38+ HLA-DR-, and (4)
      CD38+ HLA-DR+ into liquid culture media supplemented with interleukin-3 (IL-3) IL
      6, stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor,
      erythropoietin, basic fibroblast growth factor (bFGF) and insuline-like growth
      factor (IGF-1). The HSCs were found in the cell populations lacking CD38, the
      plating efficiency was highest in the CD34+ CD38- HLA-DR+ cell population (48% n
      = 12); however, only a small proportion of the CD34+ CD38- HLA-DR+ cells showed
      both lymphoid and myeloid growth potential. When the identical cell populations
      were sorted into liquid culture media supplemented with bFGF and IGF-1, cell
      growth was noted from only 1%-5% of the sorted CD34+ CD38- HLA-DR- cells. The
      cells have the potential to grow and differentiate in vitro to form complex
      structures that recapitulate normal bone formation. Serial passages of the
      progeny from these cultures resulted in the formation of similar structures.

PMID- 7527687
TI  - Optimization of the yield of PBSC for autotransplantation mobilized by high-dose
      chemotherapy and G-CSF: proposal for a mathematical model.
AB  - We analyzed the results of 71 leukapheresis procedures performed in 21 patients
      to identify the best predictive factors affecting the yield of peripheral blood
      progenitors after high-dose chemotherapy followed by G-CSF administration. An
      average of 1 +/- 1 x 10(8) MNC/kg, 5 +/- 6 x 10(4) CFU-GM/kg and 4 +/- 6 x 10(6)
      CD34+ cells/kg was collected for each leukapheresis. When we defined > or = 5 x
      10(4)/kg as the minimum number of CFU-GM per procedure for a 'satisfactory'
      collection, multiparameter analysis of clinical features and laboratory findings
      showed that the only factors that predicted the numbers of CFU-GM collected were
      prior treatment with the MOPP regimen and the number of mononuclear cells
      identified in the basophil channel of the H*1 = Technicon. A logistic regression
      analysis performed to generate a mathematical model revealed four predictive
      factors: the number of previous cycles of chemotherapy, previous MOPP
      chemotherapy, the interval from latest chemotherapy and the number of mononuclear
      cells/microliter. This model was valuable in defining the optimal time for the
      first leukapheresis procedure. In contrast, the number of circulating CD34+ cells
      did not correlate with CFU-GM numbers collected whereas the numbers of
      mononuclear cells did provide a simple and reliable index. Thus the principal
      factor affecting the efficiency of peripheral blood stem cell collection was
      prior therapy with MOPP.

PMID- 7527688
TI  - Cord blood plasma-mediated ex vivo expansion of hematopoietic progenitor cells.
AB  - Cord blood (CB) plasma has previously been found to augment the replating
      capacity of CB-derived hematopoietic progenitors. In the present study, we
      observed a 2.8 +/- 0.3 and a 1.8 +/- 0.2-fold expansion of CFU-GM in cultures of
      CB cells without growth factors but supplemented by CB plasma or maternal blood
      (MB) plasma, respectively. In the absence of growth factors, CFU-GM expansion did
      not occur in CB cell cultures supplemented with fetal calf serum (FCS),
      peripheral blood (PB) plasma, PB plasma plus concentrations of IL-6 similar to
      those previously reported in CB plasma and in bone marrow (BM) cell cultures
      supplemented with FCS, CB, MB or PB plasma. In the presence of stem cell factor
      (SCF), IL-3 and IL-11, an expansion of CFU-GM was observed in CB and BM cell
      cultures supplemented by either CB, MB or PB plasma or FCS. Nevertheless,
      progenitor expansion was significantly superior in CB cell cultures supplemented
      by CB plasma (8.7 +/- 0.7, 2.4 +/- 0.3 and 2.6 +/- 0.3-fold expansions for CFU
      GM, BFU-E and CFU-Mix, respectively). In conclusion, an unknown factor(s) present
      in CB plasma, probably capable of crossing the placenta, has an effect alone and
      in the presence of growth factors in supporting ex vivo expansion of CB
      progenitors.

PMID- 7527689
TI  - Short-term myeloid reconstitution following TBI is not adversely affected by
      doses of FK506 that abrogate lethal GVHD.
AB  - Studies were undertaken to determine whether the doses of FK506 that are
      effective for acute GVHD prophylaxis following lethal irradiation and bone marrow
      transplantation (BMT) would also suppress myeloid cell reconstitution. FK506 (3
      mg/kg/day) abrogated acute lethal graft versus host disease (GVHD) in lethally
      irradiated C57BL/10SnJ (H-2b) recipient mice given histoincompatible BM plus
      spleen cells from B10.BR (H-2k) donors and this dose was used in all of the
      studies. Endogenous and exogenous myeloid repopulation was studied in mice given
      daily injections of either FK506, an equivalent amount of carrier solvent or no
      treatment throughout the interval between total body irradiation (TBI) and the
      day of assay. Repopulation was studied after 400 or 500 cGy TBI (endogenous) and
      after 950 cGy TBI plus injection with syngeneic BM (exogenous). No consistent
      adverse effects of FK506 were seen during either exogenous or endogenous
      recovery. Parameters studied included hematocrit (Hct), WBC count, cells per
      humerus, spleen weight, splenic colony-forming units, % spleen or BM 59Fe uptake
      and colony forming cells per humerus. Similarly, when lethally irradiated
      secondary recipients were reconstituted with BM from FK506 treated primary
      recipients (lethal irradiation plus exogenous BM), no consistent effects were
      observed. These data suggest that FK506 given to prevent GVHD would not
      compromise the myeloid recovery that is critical for survival in the interval of
      time following shortly after BMT.

PMID- 7527690
TI  - Hepatitis C virus infection in thalassemia patients undergoing allogeneic bone
      marrow transplantation.
AB  - Ninety-eight patients with homozygous-beta thalassemia who had undergone
      allogeneic bone marrow transplantation (BMT) between May 1990 and March 1992 were
      tested for hepatitis C antibodies (anti-HCV) before and after BMT. Anti-HCV
      positivity was detected in 50 of the 98 patients (51%) before BMT. Seroconversion
      was demonstrated in seven of the 40 evaluable seronegative patients. In four
      cases it was probably due to the different sensitivity of first and second
      generation ELISA. Of the 46 evaluable seropositive patients 4 had transient and 5
      persistent negativity for HCV antibodies after BMT. The high prevalence of anti
      HCV positivity in thalassemic patients is related to the continuous requirement
      for blood transfusions. We found a strong correlation between biochemical and
      histological evidence of liver damage and anti-HCV positive status in multi
      transfused patients. In our experience HCV hepatitis does not influence the
      outcome of BMT.

PMID- 7527691
TI  - Rapid progression of multiple myeloma following G-CSF mobilization.
AB  - A 23-year-old man diagnosed as having multiple myeloma was treated with melphalan
      and prednisone monthly. After six cycles, an autologous peripheral blood stem
      cell transplantation (ABSCT) was planned. Peripheral blood mononuclear cells were
      collected after G-CSF mobilization (5 micrograms/kg/day for 5 days). Ten days
      after the last dose of G-CSF the patient showed a striking progression of
      multiple myeloma. A 57% infiltration of plasma cells in bone marrow and
      recurrence of laboratory abnormalities were evident. The patient's clinical
      course strongly suggests that myeloma progression was triggered by G-CSF and
      supports the concept of G-CSF mediated autocrine stimulation of myeloma growth.

PMID- 7527692
TI  - [The effect of damage to the hypothalamic suprachiasmatic nuclei in rats on the
      dynamic short-period fluctuations of their normal and abnormal behaviors].
AB  - Electrolytic lesion of the hypothalamic suprachiasmatic nuclei (SCN) increased
      the swimming activity, shortens the immobility time and decreases the depression
      rhythmic index in rats. These changes seem to be due to a disorganizing of
      functional interrelationships among the SCN, pineal gland and striatum.

PMID- 7527693
TI  - [The efficiency of heat exchange between the tissues and the blood in blood
      vessels of different diameters].
AB  - Using mathematical calculations, the processes of heat radiation of the blood
      moving along skin vessels of different diameter, were studied. The temperature of
      the blood in capillaries, small arteries and venules was shown to be equal to
      that of surrounding tissue. The data show that, under normal physiological
      conditions, a situation occurs in the skin vascular bed when the vessels on the
      diameter lesser than 100 mcm cease to be able to be heat-exchanging means in the
      skin of the living organism.

PMID- 7527694
TI  - [The spatial, bioelectrical and neurochemical characteristics of the early
      afferent reaction of the caudate nucleus to a sound stimulus].

PMID- 7527696
TI  - [The comparative effect of the action of parathyroid hormone on the mechanical
      activity of the rat myocardium in in-vivo and in-vitro experiments].

PMID- 7527695
TI  - [The unification of the diagnostic indices of the forced expiratory process].

PMID- 7527697
TI  - [Gastric motility, distensibility and adaptive relaxation in rats studied by the
      volume/pressure relationship].

PMID- 7527698
TI  - [A dual-slit photometric computerized velocity cytometer for studying the
      microvessels: the measurement principle and a description of the device].

PMID- 7527699
TI  - [A PC-based programming-apparatus unit for the single-electrode fixation of the
      membrane potential of excited cells].

PMID- 7527701
TI  - [A device for performing inhalation anesthesia on laboratory rodents].

PMID- 7527700
TI  - [Horizontal optokinetic nystagmus in the pigeon during static tilts in the
      frontal plane].
AB  - The influences of the static whole body roll tilts (30 or 45 degrees) on
      horizontal optokinetic nystagmus (HOKN) produced by optokinetic stimuli at a
      constant velocity (16 or 30 degrees/sec) were examined in the 16 pigeons. The
      significant tilt-dependent asymmetry of the tonic otolith effects on optokinetic
      system was revealed which consists in pronounced inhibitory effect of the right
      hand tilts unlike the left-hand tilts on HOKN. Separate recording of the
      oculomotor responses from the right and left eyes showed that during static roll
      tilts the temporonasal-nasotemporal (TN-NT) asymmetry of HOKN normally existing
      in the pigeon remained for the eye disposed above and was replaced by symmetric
      pattern for the eye disposed below. The results suggest the mechanism of TN-NT
      asymmetry is controlled by the otolith inputs and its function can be essentially
      modified under the influence of otolith membranes reorientation in gravity.

PMID- 7527702
TI  - [Russian-language textbooks in physiology for higher academic institutions].

PMID- 7527704
TI  - [The significance of the thyroid status of the body in realizing the adaptive
      effect of cold].
AB  - Combined immobilisation and cold for 3 and 6 hrs induced depression of cardiac
      contractile function and functional reserve, death rate of 30 and 80 per cent
      resp., hypothermia, alterations in adrenal glands and spleen, gastric mucosa
      ulceration in euthyroid rats. The changes were more obvious in hypothyroid rats.
      The cold adaptation significantly reduced the changes in the euthyroid rats
      whereas this effect was absent in hypothyroid animals. The data obtained
      corroborate the significance of intact thyroid status for the cold adaptation.

PMID- 7527703
TI  - [The effect of emotional-pain stress on the activity of carboxypeptidase N--the
      enzyme of neuropeptide processing in the rat brain].
AB  - Activity of carboxypeptidase N [correction of H] increased under emotional-algic
      stress in the rat pituitary gland and hypothalamus. Carboxypeptidase N
      [correction of H] seems to be involved in development of the stress response, and
      soluble forms of the enzyme take part in processing of secretory peptides.
      Membrane-bound forms take part in processing of the neuropeptides specific by
      their central action.

PMID- 7527706
TI  - [Lipid peroxidation in the rat brain under neurotization conditions].
AB  - Neurotization provoked a stable activation of lipid peroxidation in homogenates
      and synaptosomes of the rat brain cortex. The activation persisted for 8 days
      after cessation of the neurotization. A single short-term emotional-pain stress
      produced but a transient increase of the lipid peroxidation level.

PMID- 7527705
TI  - [The circadian dynamics of melatonin concentration in the epiphysis, plasma and
      retina of silver foxes].
AB  - A definite diurnal rhythm of the melatonin concentration was observed in the
      silver fox pineal gland, plasma and retina, with the maximum at night, the
      minimum in the morning, and intermediate values in evenings. The
      interrelationship among the melatonin levels in the tissues under study, is
      discussed.

PMID- 7527707
TI  - [The sensory components in the regulation of human respiration under functional
      loads].
AB  - A relative constancy of breathing was shown under conditions of different grades
      resistance to respiration in 11 healthy subjects even when experiencing a
      respiratory discomfort. The data suggests that the sensation is due to afferents
      from the proprioreceptors of respiratory muscles. It is corroborated by the
      constant level of initial respiratory activity at the moment of refusal from
      continuation of the test.

PMID- 7527708
TI  - [Bronchial resistance and its determining factors in middle and old age].
AB  - In 65 apparently healthy elderly and old subjects (aged 60-89) and 26 young ones
      (aged 18-35) the bronchial resistance (Raw) was determined by means of
      simultaneous recording of esophageal pressure and a pneumotachogram. In the aged
      an increase of Raw, especially during expiration, and a decrease in specific
      conductance of lungs were found. In the group of young subjects the Raw was
      increased in women. In the aged the sex differences in Raw were levelled.

PMID- 7527709
TI  - [Changes in the sensitivity of the human respiratory system to hypercapnic and
      hypoxic stimuli during repetitive exposures to physical loads of different
      intensities].
AB  - Variability of the responses to CO2 and hypoxia was revealed in strenuous
      physical load. The dynamics of the CO2 responses was found to be regular during
      the recreative periods specific for training sessions in cycling sports. Changes
      of the CO2-H+ response seem to be determined by optimisation of the CO2 dynamics
      in the body.

PMID- 7527710
TI  - [Free-radical processes in the lung tissue of rats under hyperbaric oxygenation
      and in the posthyperoxic period].
AB  - An increased antioxidation enzyme activity and a low level of the peroxidation
      products were revealed in exposure to low oxygen pressure and 1 to 7 days after
      it in rats. The data obtained suggest presence of a powerful antioxidant system
      in the rat lung.

PMID- 7527712
TI  - [The effect of the perfusates from tetanized donor slices on the induction of
      long-term potentiation in recipient slices].
AB  - Perfusate collected during tetanic stimulation of the lateral olfactory tract
      from the donor rat olfactory cortex induced long-term changes of the focal
      potentials in recipient slices: the perfusate of the depression response to the
      tetanization-induced potentiation, and vice versa, in the recipient slices. The
      donor slices seem to release some active substances during tetanization which are
      able to modulate the electric activity in the recipient slices.

PMID- 7527711
TI  - [Patterns of erythropoietic reconstruction in the erythroblastic islands].
AB  - A decrease in the erythroid cell number in the erythroblastic island's crown
      seems to be an important factor for involvement of early erythroid cells in the
      contact with macrophages of maturing erythroblastic islands. The erythropoietin
      stimulation increases the affinity of these macrophages to the erythroid
      progenitor cells.

PMID- 7527713
TI  - [The possible role of acid glycosaminoglycans in maintaining erythropoiesis in
      the bone marrow erythroblastic islands].
AB  - The dynamics of changes in the contents of acid glycosaminoglycans in stimulation
      of the erythropoiesis was compared with the degree of maturity of the
      erythroblastic islands' erythroid cells. Blood loss was found to increase the
      contents of acid glycosaminoglycans in the central macrophages of the
      erythroblastic islands.

PMID- 7527714
TI  - [The temperature-sensitive function of the skin mechanoreceptor endings].
AB  - Impulse activity of the ischiatic nerves single fibres in response to focused
      ultrasound stimulation of the rat hind-foot receptive fields, was studied. The
      receptor units were divided into low-, average- and high-threshold groups by the
      value of their threshold responses. No impulse activity was revealed in response
      to direct action of cold or warm water on the foot in the afferent fibres. Warm
      stimulation evoked most obvious changes in the low-threshold units, whereas
      latency noticeably changed in the average-threshold, and potential activity--in
      the high-threshold units rather. The data suggests involvement of the average
      threshold units in the temperature perception.

PMID- 7527715
TI  - [The pattern of body temperature changes during cooling in relation to the
      properties of its covering (mathematical research)].
AB  - A sphere model simulating the rabbit organism was subjected to the effects of ice
      cold water and cold air (0 degrees C). Distributions of the temperature within
      the sphere and its membrane depending on the thickness of the membrane, are
      presented. A 3.6-fold increase in the sphere heat-production resulted in
      maintenance of a normal average temperature (37 degrees C) within the sphere.

PMID- 7527716
TI  - [Role of IGF system in the ovary].
AB  - The stimulating effect of Insulin-like Growth Factors (IGFs) on ovarian
      folliculogenesis is modulated by binding proteins (IGFBPs). During follicular
      growth, levels of IGFBP-2, -4 and -5 decrease in follicular fluid. These changes
      are a consequence of a decrease in synthesis and of a degradation by gonadotropin
      stimulated specific proteases. They lead to an increase in the bioavailability of
      IGFs and their action on granulosa cells. By contrast, follicular atresia is
      characterized by a high increase in the synthesis and levels of IGFBPs < 40kDa,
      and by a dramatic decrease in IGFs bioavailability. Finally, at least part of
      intrafollicular IGFs and IGFBP-3 may be derived from the circulatory pool. Their
      levels only change slightly during follicular growth and atresia.

PMID- 7527717
TI  - EMRSA-16 continues to spread.

PMID- 7527718
TI  - Typing of Staphylococcus aureus.

PMID- 7527719
TI  - AIDS and HIV-infection in the United Kingdom: monthly report.

PMID- 7527720
TI  - Human hemoglobin conjugated to carboxylate dextran as a potential red blood cell
      substitute. II--Pharmacotoxicological evaluation.
AB  - A solution of human hemoglobin bound to benzene tetracarboxylate substituted
      dextran, whose physicochemical characteristics are defined in part I, was
      evaluated in vivo as a potential red blood cell substitute. Further experiments
      show: - the confirmation of a lack of acute toxicity in mice and guinea pigs
      after injection of 12.5%, 25% and 50% of the blood mass and the absence of death
      in rabbits having undergone three successive 25% hemorrhagic shocks in three week
      intervals. A plasma half-life of 9.5 +/- 0.5 hours in 70-75% hemorrhagic shocks
      on guinea pigs and the absence of dex-BTC-Hb in thoracic and abdominal cavities.
      No tissue oedema was noticed. Total hemoglobinuria did not exceed 10% of the
      injected hemoglobin quantity and only involved free hemoglobin. A lack of death
      in 70-75% hemorrhagic shocks and survival times ranging from 10 hours to 3 days
      in total exchange transfusions in guinea pig experiments.

PMID- 7527721
TI  - Methemoglobin formation after administration of hemoglobin conjugated to
      carboxylate dextran in guinea pigs. Attempts to prevent the oxidation of
      hemoglobin.
AB  - In 1990, McGown demonstrated in vitro a limitation of extracellular methemoglobin
      (metHb) formation by releasing and recycling of ascorbic acid by red blood cells.
      In order to investigate the autoxidation of free or modified hemoglobin in plasma
      and the possibility of reproducing McGown's phenomenon in vivo, we performed a
      50% blood mass exchange in guinea-pigs with a 70 +/- 5 g/l dex-BTC-Hb solution
      (metHb < 5%). Methemoglobin was determined according to Evelyn-Malloy's method.
      We observed a clear but limited oxidation of plasmatic hemoglobin (MetHb
      approximately 30-40% at t = 12 hrs up to t = 24 hrs). A similar blood mass
      exchange was performed with the same hemoglobin solution which was previously
      totally oxidized into metHb. 40% of this methemoglobin was found to be reduced
      after 12 hrs. These results demonstrated a marked reducing activity by residual
      blood as shown by others. The addition of potentially protective compounds such
      as ascorbic acid (non enzymatic intraerythrocytar reduction pathway), methylene
      blue or riboflavin (enzymatic intraerythrocytar pathway), allowed a significant
      drop in the methemoglobin level. On the contrary, we didn't observe any reducing
      effect with reduced glutathione.

PMID- 7527722
TI  - Acellular and cellular hemoglobin solutions as vasoconstrictive factor.
AB  - The inhibitory effects of acellular and cellular hemoglobin (Hb) solutions on
      endothelium-dependent vasorelaxation were investigated in rabbit thoracic aortic
      strips. As acellular Hb solutions, 2,3-diphosphoglycerate (DPG)-depleted Hb and
      pyridoxylated Hb were examined. Cellular Hb solutions included washed human fresh
      red cells and liposome Hb encapsulated with pyridoxal-5'-phosphate (PLP). The
      tissues were precontracted with phenylephrine (PE), after which acetylcholine
      (ACh) was added to elicit a steady-state relaxation. Acellular Hb solutions
      cumulatively reversed ACh-induced relaxation, and these inhibitory effects
      reached a plateau at 10 micrograms/ml. Increasing oxygen affinity by
      pyridoxylation had little effect on this. In contrast, both red cells and
      liposome Hb solution showed moderate inhibitory effects, and they reached a
      plateau at 1 mg/ml. These findings indicate that acellular Hb solutions are more
      potent inhibitors than cellular Hb solutions by a factor of about 100, and that
      the encapsulation of Hb is a preferable method to mimic the red cell.

PMID- 7527723
TI  - Human hemoglobin conjugated to carboxylate dextran as a potential red blood cell
      substitute. I. Further physico-chemical characterization.
AB  - In a previous paper, we described the preparation of a conjugate by reaction of
      benzene tetracarboxylate-substituted dextran (dex-BTC) with oxyhemoglobin. The
      first biological experiments carried out on animals showed that a solution of
      this type of product could be regarded as an oxygen-carrying fluid. The physico
      chemical properties of this conjugate have been further characterized in view of
      its potential application in clinical experiments. Its molecular size
      distribution and the fraction of intramolecularly cross-linked hemoglobin were
      determined by elution on various types of chromatographic columns. Moreover the
      conjugate's oxygen-binding properties were studied in the presence of effectors
      and of Cl- ions, and the results showed that the allosteric site and the Val 1
      alpha residues of conjugated hemoglobin were occupied by dex-BTC. Finally, the
      fractions obtained after gel filtration exhibited a similar P50 whatever their
      molecular sizes. So far, all the results obtained are compatible with the use of
      the conjugate solution as a blood substitute.

PMID- 7527724
TI  - Hemoglobin is a late event in the differentiation of Friend erythroleukemic cells
      in-vitro. I. The role of interferon-induced proteins.
AB  - Here we report that the interferon (IFN)-induced proteins, 2'-5'-oligoadenylate
      synthetase (OAS) and IFN-induced protein kinase (PKI), appearance and activity
      precede that of hemoglobin (Hb) in the differentiation process of Friend
      erythroleukemic cells (FLC). Since our results are correlative, we assume that
      OAS and PKI are activated, and act at an early stage in the differentiation
      process, enabling the late onset of Hb synthesis. It is, thus, suggested that red
      blood cells harboring specific differentiating genes may be used as more
      efficient carriers of oxygen-binding molecules.

PMID- 7527726
TI  - Structure and dynamics from solid state NMR spectroscopy.

PMID- 7527725
TI  - Functional capillary density changes during blood substitution with alpha alpha
      Hb and dextran 70: influence on oxygen delivery.
AB  - The effectiveness of a blood substitute is ultimately determined by the rate at
      which O2 arrives to the capillaries and the functional capillary density i.e.,
      the number of flowing capillaries per unit volume of tissue. We use this
      rationale to analyze the effectiveness of isovolemic blood substitution with
      alpha alpha Hb (3,5-bis(dibromosalicyl)fumarate) compared to isooncotic and
      isovolemic hemodilution with dextran 70. Progressive hemodilution with each
      solution was performed in the awake hamster skinfold model by simultaneous
      isovolemic exchange of blood until the systemic hematocrit was reduced to 30% of
      control. Systemic hematocrit, blood pressure, heart rate were monitored. To
      determine O2 delivery at the microcirculatory level, functional capillary
      density, RBC velocity, RBC flux, capillary hematocrit were measured. Functional
      capillary density was maintained during moderate hemodilution with dextran 70,
      whereas alpha alpha Hb exchange caused a gradual reduction in the number of
      flowing capillaries. O2 delivery to tissue was calculated from total O2 content
      (RBC and plasma Hb or RBC only), blood flow, and functional capillary density.
      Our findings suggest that augmentation of the O2 content of blood with alpha
      alpha Hb substitution produces similar results in terms of capillary O2 delivery
      and capacity as isovolemic and isooncotic hemodilution with dextran 70.

PMID- 7527727
TI  - [Physiopathological role of low affinity IgE receptor (CD23) in hematopoietic
      cells].
AB  - Ligation of the low affinity IgE receptor by specific monoclonal antibodies or
      multivalent IgE complexes result in the transduction of signals which differ
      according to the CD23 isotype expressed by the various cell types. In B
      lymphocytes, it elicits the early activation of phospholipase C through a
      mechanism involving a G-protein insensitive to Pertussis toxin, followed by a
      late phase of cAMP accumulation. In monocytes, which express the CD23b isoform,
      ligation of CD23 was also found to induce a delayed accumulation of cAMP, that
      was largely dependent on a prior cGMP increase through a mechanism involving the
      activation of a NO synthase. This pathway, which appears to be exacerbated in
      allergic diseases, seems to play an important role in the differentiation of
      cells of the monocytic lineage, their capacity to release proinflammatory
      mediators and their cytotoxic functions.

PMID- 7527730
TI  - Branch retinal vein occlusion and chorioretinal anastomosis following
      photocoagulation of a choroidal neovascular membrane.

PMID- 7527728
TI  - [Mutation of p53 gene and expression of alphafetoprotein during
      hepatocarcinogenesis].
AB  - To investigate the expression of mutant p53 protein (mP53) and alpha-fetoprotein
      (AFP) during hepatocarcinogenesis, we detected immunohistochemically the
      specimens from 4 cases of normal human liver, 5 of cirrhosis, 5 of adenomatous
      hyperplasia (AH), and 16 of hepatocellular carcinoma (HCC) (by Edmondson
      classification. The 4 cases with normal liver showed negative mP53 and AFP. Four
      of the 5 cirrhosis cases were positive for mP53 and AFP. In 5 AH cases, 4 were
      positive for mP53 and AFP. In the 4 cases of grade I HCC, 2 were positive for
      mP53 and AFP. In the 6 cases of grade II HCC, 4 were positive for mP53 and AFP.
      In the 6 cases of grade III HCC, 1 showed mP53 positive staining but negative
      AFP, and 2 were negative for mP53 but positive for AFP, while 3 were negative for
      both mP53 and AFP. The results indicated that the mutation of p53 gene occurred
      in the early stage of hepatocarcinogenesis, and may be correlated with the
      initiation of hepatocarcinogenesis, and that mutant p53 protein probably related
      to the reactivation of AFP gene.

PMID- 7527731
TI  - Immune responses against self-TCR peptides.
AB  - Vaccination of rats against the TCR peptide V beta 8.2 (39-59) was reported to
      inhibit the immunopathogenic process of EAE. Analysis of the immune response to
      this peptide and several related TCR peptides yielded the following findings: (i)
      Lewis rats immunized in vivo and challenged in vitro responded with vigorous
      lymphocyte proliferative responses to peptide V beta 8.2 (39-59) and to three
      other rat TCR peptides, V beta 8.3 (15-32), V beta 8.3 (39-59), and V beta 14 (39
      59). On the other hand, two other rat peptides, V beta 8.2 (18-38) and V beta 8.3
      (62-76), were poorly immunogenic. (ii) Rat peptide V beta 8.2 (39-59) was found
      more immunogenic than its mouse homolog, in both Lewis rats and B10.A mice. A
      moderate level of cross-reactivity was observed between these two peptide
      homologs. (iii) Rats of different genetic makeups varied in their response to
      peptide V beta 8.2 (39-59). A similar pattern of response of the different rats
      was found with another TCR peptide, V beta 14 (39-59). Hybrids between high and
      low responder rat strains resembled the high responders in their response to the
      TCR peptides. (iv) Sensitized lymph node cells as well as lymphocytes of a cell
      line specific for peptide V beta 8.2 (39-59) failed to respond to T cells that
      express the V beta 8.2 gene product. This observation is interpreted to indicate
      that peptide V beta 8.2 (39-59) is a cryptic determinant of the V beta 8.2
      protein. Moreover, the data suggest that lymphocytes proliferating against
      peptide V beta 8.2 (39-59) may not be responsible for the reported inhibition of
      EAE in rats vaccinated with this peptide.

PMID- 7527732
TI  - M-VEC (methotrexate, vinblastine, epirubicin, and cisplatin) with granulocyte
      colony-stimulating factor for the treatment of urothelial cancer: an effective
      and safe chemotherapy regimen.
AB  - The toxicity of combination chemotherapy is significant, with the most prominent
      side effect being myelosuppression. To reduce the toxicity, we used a recombinant
      human granulocyte colony-stimulating factor (rhG-CSF). A total of 52 patients
      were enrolled in this study. The sites of tumor involvement included the urinary
      bladder in 24 patients, the renal pelvis in 5, the ureter in 4, lymph nodes in
      11, bone in 4, the lung in 1, and miscellaneous sites in 4 patients. The
      chemotherapy was given in 21-day cycles as follows: 30 mg/m2 methotrexate was
      given intravenously on day 1, and approximately 24 h later, 3 mg/m2 vinblastine,
      30 mg/m2 epirubicin, and 70 mg/m2 cisplatin were given intravenously. The rhG-CSF
      (2 micrograms/kg per day) was injected subcutaneously on days 3-16 of each cycle.
      All patients received full doses of the antineoplastic agents on time according
      to the protocol design. The response rates were 61% for primary sites, 55% for
      lymph nodes, 0 for bone, and 67% for miscellaneous sites. Of 42 patients
      evaluated, 5 (12%) achieved a complete response and 20 (48%) achieved a partial
      response, for an overall response rate of 60%. Of the 42 patients, 27 (64%) are
      alive, and the median duration of survival is 14 months. The mean nadir white
      blood count was more than 5,600 cells/mm3. The incidence of mucositis in the
      total toxic symptoms was low. There was no cardiac toxicity or drug-related
      death. These results indicate that the present combination chemotherapy with
      coadministration of rhG-CSF is an effective and safe regimen for the treatment of
      urothelial cancer.

PMID- 7527729
TI  - [The expression of hepatitis C antigen in hepatitis and liver cancer tissues].
AB  - 30 specimens of hepatocellular carcinoma (HCC) from laporotomy biopsy and 15
      specimens of hepatitis from aspiration biopsy were subjected to hepatitis C (HCV)
      immunohistochemistry. Anti-HCV core monoclone antibodies and ABPAP detection
      method were used. The results showed that 5 specimens (17%) in the HCC group and
      3 (20%) in the hepatitis group were positive, with a total positive rate of 18%.
      The expression pattern was scattered, located in the cytoplasm. There were
      positive signals in the para-carcinomatous tissues of the 5 positive cases of
      HCC, and there were scattered positive signals just inside the cytoplasm of the
      cancer cells in 3 positive HCC specimens.

PMID- 7527733
TI  - Chemotherapy for endocrine-therapy-refractory prostate cancer.
AB  - The effects of various chemotherapy regimens on endocrine-therapy-refractory
      prostate cancer were examined in 64 patients. Chemotherapy was started from the
      first evidence of relapse. The regimens of the initial chemotherapy were as
      follows: cisplatin (CDDP, 4 cases) and ifosfamide (4 cases) were given as single
      agents and vincristine, ifosfamide, and peplomycin (VIP, 8 cases);
      cyclophosphamide, doxorubicin, and CDDP (CAP, 14 cases); ifosfamide, doxorubicin,
      and CDDP (IAP, 24 cases); and etoposide, doxorubicin, and CDDP (EAP, 10 cases)
      were given as combinations. On the basis of the results, the patients were
      divided into two groups: single agents plus VIP and other combinations. In the
      CAP, IAP, and EAP groups, the cause-specific survival was similar, and the
      survival of these groups was longer than that of the single agents plus VIP
      group. Since patients with a long duration between the start of endocrine therapy
      and the start of chemotherapy were contained in the CAP, IAP, and EAP groups,
      comparison was performed without these cases. No difference was found between the
      two groups, suggesting that no superior regimen was found. The short-term effect
      was evaluated on the basis of the changes observed in prostate-specific antigen
      (PSA) and prostatic acid phosphatase (PAP) levels at 3 months after the start of
      chemotherapy, and patients showing a complete response, partial response, or no
      change on any of the regimens exhibited longer survival than did those with
      progressive disease. Since the PSA doubling time estimated before the
      chemotherapy correlated with the change in the PSA values due to the
      chemotherapy, the rate of proliferation of the tumor influenced the effect of the
      chemotherapy. Thus, this finding suggests that slowly growing cancers show a
      better response to chemotherapy than do rapidly proliferating ones.

PMID- 7527734
TI  - Intra-arterial chemotherapy using a reservoir for endocrine-refractory prostate
      cancer.
AB  - For local control in patients with endocrine-refractory prostate cancer, an intra
      arterial chemotherapy regimen comprising methotrexate (MTX), Adriamycin (ADM),
      and cisplatin (CDDP) was evaluated. A total of 19 patients having a mean age of
      66.4 +/- 8.8 years and a mean performance status (PS) of 1.3 +/- 1.0 were
      enrolled. Of these patients, 3 had proved to be resistant to initial endocrine
      therapy and the remaining 16 had relapsed from disease stabilization after
      endocrine therapy. The catheter tip was placed in the internal iliac artery in 16
      cases, in the common iliac artery in 2 cases, and in the aorta in 1 case after
      occlusion of the contralateral feeding artery. The intraarterial chemotherapy was
      performed mainly using MTX (30 mg/m2), ADM (30 mg/m2), and CDDP (50 mg/m2) as one
      course and was repeated for a mean of 2.9 +/- 2.3 courses. Then, in an outpatient
      clinic, 5-fluorouracil (5-FU), ADM, or MTX was given intra-arterially as
      maintenance chemotherapy until re-relapse. As based on the criteria for
      evaluation of nonsurgical therapy in prostate cancer proposed by the Japanese
      Urological Association, the prostatic lesion showed a partial response (PR) in 9
      cases and no change (NC) in 10 cases. As judged from the response of prostate
      specific antigen (PSA), a complete response (CR) was obtained in 6 cases, a PR,
      in 3 cases; and NC and progressive disease (PD), in 2 cases each. Therefore, the
      overall response rate was 63%. Improvement in the symptoms was observed in 83% of
      patients. The duration of the response was 15.1 +/- 10.5 months for the PR cases
      and 7.4 +/- 5.7 months for the NC cases. Furthermore, the mean survival time
      observed in the PR group was 38.9 months, which was better than that seen in the
      NC (16.4 months) and PD (10.5 months) groups. These results suggest that intra
      arterial chemotherapy may become an option for the treatment of locally advanced
      and endocrine-refractory prostate cancers. Using a reservoir, this chemotherapy
      can be easily given in an outpatient clinic.

PMID- 7527736
TI  - Adjuvant and neoadjuvant chemotherapy for invasive bladder cancer.
AB  - A total of 20 patients with primary invasive bladder cancer who underwent radical
      cystectomy received postoperative adjuvant chemotherapy using a CAP
      (cyclophosphamide, doxorubicin, and cisplatin) or modified M-VAC (methotrexate,
      vinblastine, pirarubicin, and cisplatin) regimen. In all, 16 of the patients were
      treated with CAP and 4 received the modified M-VAC regimen. Of the 20 patients,
      17 had transitional-cell carcinoma with or without non-transitional-cell
      elements. All of the patients had tumors with a histological grade of G2 (6
      cases) or G3 (14 cases). As for lymph-node metastasis, there were ten N0 cases,
      three N1 cases, six N2 cases, and one N3 case. Adjuvant chemotherapy was usually
      commenced 2 weeks after the surgery and was given every 3-4 weeks for two or
      three cycles. The 5-year survival rate of these 20 patients was 65.9%, whereas
      that of 49 patients who did not receive any adjuvant chemotherapy was 30.2%.
      Regarding toxicity, both of the adjuvant chemotherapy regimens used in this study
      were generally well tolerated. The most common toxic effects were
      gastrointestinal symptoms, alopecia, and myelosuppression. Another 19 patients
      with invasive transitional-cell carcinoma of the bladder received 2 or 3 cycles
      of neoadjuvant chemotherapy using the modified M-VAC or MEC (methotrexate,
      epirubicin, and cisplatin) regimen. Of 18 pathologically evaluable patients who
      underwent radical cystectomy or partial cystectomy, the stage was pT0 in 3 cases
      (17%), pTis in 3 (17%), pT1 in 3 (17%), and pT2 or higher in 9 (50%). The 4-year
      survival rate of 18 patients who received neoadjuvant chemotherapy was 71.5%.
      Regarding toxicity, one patient died of a bowel complication after surgery, and
      the complication was suggested to be drug-induced.

PMID- 7527735
TI  - The effect of dose intensity on M-VAC therapy for advanced urothelial cancer.
AB  - M-VAC therapy (methotrexate, vinblastine, Adriamycin, and cisplatin) has improved
      the treatment results of urothelial cancer patients. However, it is sometimes
      complicated by drug toxicities, including bone marrow suppression. We analyzed
      the relative dose intensity in each patient undergoing M-VAC chemotherapy in
      relation to the chemotherapeutic effect and survival. In addition, the role of
      granulocyte colony-stimulating factor (G-CSF) in the dose intensity of M-VAC
      therapy was analyzed. Between June 1988 and March 1993, 29 patients with advanced
      urothelial cancer were treated with M-VAC therapy in our institution. Of 18
      patients with evaluable lesions, 2 (11.1%) showed a complete response (CR) and 7
      (38.9%) showed a partial response (PR), and the overall response rate was 50.0%.
      The median follow-up period for these 18 patients was 14.6 months and the median
      survival was 8.7 months, with 12 of the 18 patients being alive at the time of
      analysis. The relative dose intensity (RDI) for these 18 patients was 0.81 for
      methotrexate, 0.80 for vinblastine, 0.92 for Adriamycin, and 0.91 for cisplatin,
      for a mean RDI of 0.87. There was no correlation between the chemotherapeutic
      effect and the RDI. When we calculated the RDI for all 29 patients who underwent
      M-VAC therapy, G-CSF increased the RDI of Adriamycin significantly. The results
      of this retrospective study indicate that a dose intensity for M-VAC therapy in
      the range of 0.61-1.00 is unlikely to correlate with the chemotherapeutic effect,
      although G-CSF contributes to increasing the RDI of Adriamycin.

PMID- 7527737
TI  - Neuropeptides in nasal mucosa.

PMID- 7527738
TI  - Increased soluble CD14 serum levels and altered CD14 expression of peripheral
      blood monocytes in HIV-infected patients.
AB  - Serum levels of soluble CD14 were elevated in HIV-infected asymptomatic patients
      or those with lymphadenopathy (CDC II/III) 2.9 +/- 0.8 mg/l compared with normal
      controls with 2.2 +/- 0.47 mg/l, P < 0.001. A further rise was seen in patients
      with ARC (CDC IVA) 3.8 +/- 1.1 mg/l, P < 0.01 and patients with AIDS (CDC IVB-D)
      5.7 +/- 2.5 mg/l, P < 0.01. Although absolute numbers of CD14+ cells decrease in
      the AIDS group, the percentage of CD14+ monocytes did not change. In contrast,
      levels of soluble T cell antigens sCD4 and sCD8, which are higher in HIV-infected
      patients compared with normal subjects, showed no increase with disease
      progression. Serum levels of sCD14 were correlated positively with beta 2
      microglobulin levels (rs = 0.63, P < 0.0001). Whereas the percentage of CD14+
      monocytes did not change, an increase in monocytic CD14 expression in HIV
      infected patients was observed (P < 0.01). The percentage of a monocyte subset
      expressing both CD14 and CD16 increased from 6% in normal healthy persons to 13%
      in HIV-infected patients (P < 0.001), and did not vary between the HIV patient
      groups. Incubation of cultured peripheral blood monocytes with azidothymidine had
      no effect on either normal or LPS-induced or IL-4-inhibited sCD14 release in
      vitro. Therefore, an effect of AZT on sCD14 serum values in vivo is considered to
      be unlikely. Our data further provide evidence that monocytes/macrophages are
      engaged in HIV infection.

PMID- 7527739
TI  - Antigenic structure of the hepatitis C virus envelope 2 protein.
AB  - The antigenic structure of the envelope 2 (e2) protein of the hepatitis C virus
      (HCV) was characterized by the use of 70 synthetic peptides and 131 human sera
      from persons with antibodies to HCV. Among 34 overlapping peptides spanning the
      e2 protein of HCV, two major antigenic regions were located to residues 484-499
      and residues 554-569. The sequence of the two major antigenic regions of the e2
      protein are partly well conserved within the described types of HCV. Both regions
      contain two Cys residues in close proximity, and the region at residues 554-569
      contains a putative N-glycosylation site, which are factors that previously have
      been suggested to affect the immune recognition of the e2 protein. Using
      substitution peptide analogues where each position within residues 484-499 and
      554-569 were sequentially substituted by Ala or Gly, the most essential residues
      for antibody binding were found to be the Pro-498, Ala-499, Ala-566, Pro-567, and
      Pro-568. All of these, except for the Pro-498 and Ala-566, are conserved among
      different HCV strains. Also, according to previous studies, position 496 often
      shows variations, which could be explained by position 496 being contained within
      the antigenic region at residues 484-499. Interestingly, none of the Cys residues
      at positions 486, 494, 564 and 569 were found to be essential for antibody
      binding, indicating that these are not essential in maintaining the e2
      antigenicity of the peptides. In a material of 114 confirmed anti-HCV positive
      sera, derived from patients during the acute or the chronic phase of HCV
      infection, the prevalence of antibodies to the two major linear antigenic regions
      of the e2 protein was found to be 55% among HCV RNA-positive sera, and 53% among
      HCV RNA-negative sera. In conclusion, we have identified and characterized two
      major linear antigenic regions outside the two hypervariable regions of the e2
      protein. Since these regions are accessible to the B cells of the infected host,
      these two regions are likely to be surface exposed either on the precursor
      polyprotein or the native e2 protein. Also, we could confirm that antibodies to
      the e2 protein co-exist with HCV viraemia.

PMID- 7527740
TI  - Sequential autoantigenic determinants of the small nuclear ribonucleoprotein Sm D
      shared by human lupus autoantibodies and MRL lpr/lpr antibodies.
AB  - Autoantibodies directed against the Sm proteins of the spliceosome complex are
      found in approximately 25% of systemic lupus erythematosus (SLE) patients sera.
      To determine which regions of the Sm D polypeptide are involved in the lupus
      autoimmune response, binding to overlapping octapeptides of Sm D has been
      evaluated with sera from nine Sm D-positive patients, six patients with other
      autoimmune serology, and five normal human sera. Lupus patient sera which are Sm
      precipitin-positive bind various combinations of five regions of the peptide. The
      major antigenic region, Epitope 5 (REAVA(GR)10GGPRR), is bound by eight of nine
      Sm precipitin-positive sera tested. This region of Sm D shows significant
      sequence homology with Epstein-Barr nuclear antigen-1. To determine the fine
      specificity of the murine Sm response, four unique Sm D MoAbs derived from MRL
      lpr/lpr mice and three adult anti-Sm-positive MRL lpr/lpr mouse sera have been
      analysed. Two of these monoclonals, KSm 4 and Y12, as well as the MRL lpr/lpr
      sera tested, show binding with Epitope 5. Another of these monoclonals, KSm 2,
      binds octapeptides 84-91, DVEPKVKSKKREAVAG, which corresponds to Epitope 4 of
      this study. Antibodies from SLE patients with autoimmune serology other than anti
      Sm bind the carboxyl glycine-arginine repeat (GR)10 peptides of Sm D. However,
      none of the antibodies tested from patients who do not have lupus and who have
      different autoimmune serology binds any of the Sm D octapeptides. Normal controls
      did not significantly bind any of the Sm D octapeptides. These results describe
      two major regions of shared antigenicity of Sm D between sera from SLE patients
      and MRL lpr/lpr mice, thereby establishing a basis for the cross-species
      similarity of autoimmunity to the Sm autoantigen in SLE.

PMID- 7527741
TI  - Anti-CD5 therapy decreases severity of established disease in collagen type II
      induced arthritis in DBA/1 mice.
AB  - Collagen-induced arthritis has been widely used as an animal model of rheumatoid
      arthritis. We have used this model with a view to determining potential
      therapeutic targets for the treatment of human disease. To do this we have
      attempted to modulate the progression of established arthritis over a 10-day time
      period following the first appearance of disease, by i.p. injection of one of
      three different MoAbs. These consist of a rat IgG2a specific for the CD5 antigen
      expressed on all T cells and a subpopulation of B cells, a mouse IgG2b
      recognizing the CD72 antigen, and a rat IgM specific for the B220 molecule, CD72
      and B220 both being expressed on all B cells. None of the three MoAbs had
      depleting activity in vivo. The progression of arthritis was monitored both
      clinically, and histologically. The effects of treatment with anti-CD5 and anti
      CD72 antibodies were compared with control antibodies of the same species class
      and subclass. In the case of anti-B220 antibodies, the effects of treatment were
      compared with administration of PBS. Of these MoAbs, only treatment with anti-CD5
      resulted in disease amelioration with significant decrease in disease severity in
      60% of the animals. These changes became apparent 6 days after initiation of
      treatment. There were no significant differences in serum levels of IgG
      antibodies to native bovine collagen type II between the groups of treated and
      control mice. Possible mechanisms underlying the modification of disease
      expression following treatment with anti-CD5 MoAb are discussed.

PMID- 7527743
TI  - Tryptic peptides of human thyroglobulin: II. Immunoreactivity with sera from
      patients with thyroid diseases.
AB  - Tryptic peptides of human thyroglobulin (Tg) were analysed by Western immunoblot
      for their reactivity to circulating autoantibodies from patients with Hashimoto's
      thyroiditis (HT), Graves' disease (GD) and thyroid carcinoma, and from normal
      human controls. Low molecular weight peptides were released after 4 h incubation
      of Tg with trypsin. The sera of thyroid disease patients reacted with several
      peptides, but predominantly bound three peptides with apparent molecular weights
      (MWap) of 25 kD, 20 kD, and 15 kD; the sera of normal individuals did not bind
      these fragments of Tg. The pattern of tryptic peptides recognized by the majority
      of sera from GD patients differed from that recognized by sera from most patients
      with HT. Autoantibodies from both groups of patients recognized a 15-kD peptide
      with a high frequency, but the sera from 26/43 (60%) GD patients also recognized
      a peptide with MWap of 25 kD, whereas the sera from 22/35 (63%) of HT patients
      recognized a 20-kD peptide. A few sera from patients with thyroid carcinoma
      reacted with peptides with MWap of 15 and 20-kD, and none bound the 25-kD
      peptide. The immunoreactivity of autoantibodies in HT sera to the 20-kD peptide
      paralleled the competitive inhibition of the MoAb 137C1 by these sera. In
      addition, MoAb 137C1 and Hashimoto's sera showed the same Western immunoblot
      binding pattern to Tg tryptic peptides, suggesting that a Hashimoto-associated
      epitope and the 137C1-binding site are found on the same peptide. These findings
      suggest that distinct peptides are recognized by Tg autoantibodies from patients
      with different thyroid diseases.

PMID- 7527742
TI  - Tryptic peptides of human thyroglobulin: I. Immunoreactivity with murine
      monoclonal antibodies.
AB  - Human thyroglobulin (Tg) was treated with trypsin at different concentrations of
      trypsin/Tg for various incubation times at 37 degrees C using non-reducing
      conditions. A ratio of trypsin to Tg of 1:100 (w/w) was optimal to release small
      peptides that were reactive to murine MoAbs to human Tg. Most peptides were
      released after only 1 h incubation with trypsin, but these peptides were further
      degraded at longer incubation times. However, a few small peptides, the largest
      of which with an apparent molecular weight (MWap) of 40 kD, resisted tryptic
      digestion up to at least 12 h of incubation. These resistant peptides were
      further degraded by trypsin at 18-24 h of incubation. Tryptic peptides of Tg,
      released at 1 h and 4 h of incubation, were analysed for their immunoreactivity
      to 16 well characterized anti-Tg MoAbs by Western immunoblot. Patterns of peptide
      recognition of these MoAbs were generally unique. Eight MoAbs reacted with
      peptides of MWap of 10-25 kD and above. Four other MoAbs reacted with peptides of
      MWap of 25-43 kD and above, and the remaining four reacted with peptides of MWap
      > 43 kD. Nine of these MoAbs failed to recognize peptides after reduction,
      suggesting that the MoAbs bind conformation-dependent epitopes. The above
      information will promote the development of models relating the structure of Tg
      to the autoimmune process, and may provide an understanding of those regions of
      Tg responsible for the induction of autoimmune thyroiditis.

PMID- 7527744
TI  - Characterization of neural cell adhesion molecule (NCAM) expression in thyroid
      follicular cells: induction by cytokines and over-expression in autoimmune
      glands.
AB  - NCAM (CD56) is a cell surface glycoprotein of the immunoglobulin superfamily
      expressed on neuroendocrine and natural killer (NK) cells which has considerable
      molecular heterogeneity due to differential splicing and post-translational
      modifications. NCAM has been detected in the thyroid follicular cells
      (thyrocytes) immunohistologically. We report here the molecular form, the
      modulation by cytokines and the levels of expression in thyroid pathology. By
      using a panel of MoAbs to NCAM on Western blots from thyrocyte extract we have
      determined that these cells express the 140- and 180-kD forms of NCAM. Exposure
      of primary cultures of thyrocytes to interferon-gamma (IFN-gamma), and even more,
      to the combination of IFN-gamma plus tumour necrosis factor-alpha (TNF-alpha)
      induced a clear increase in the expression of NCAM as assessed by FACS analysis.
      NCAM expression in thyrocytes was assessed by immunofluorescence in 59 surgical
      specimens of thyroid glands, and was found increased in 11/17 (64%) of Graves',
      in 5/25 (20%) of multinodular goitre (MNG) and in occasional adenoma glands. No
      correlation was found with the expression of HLA class I, class II or the degree
      of lymphocytic infiltration scored in adjacent sections, but it was often seen in
      areas infiltrated by macrophages. In conclusion, NCAM is an adhesion molecule
      whose expression is clearly increased in thyrocytes in autoimmune glands,
      probably as a consequence of exposure to cytokines locally released. Since one of
      the forms of NCAM expressed by thyrocytes has the capability to generate
      intracellular signal it may play a role in normal thyroid function. In addition,
      NCAM may facilitate the recognition of thyrocytes by lymphocytes, particularly by
      NK CD56+ lymphocytes.

PMID- 7527745
TI  - Impact of 15-deoxyspergualin on effector cells in experimental autoimmune
      diseases of the nervous system in the Lewis rat.
AB  - The influence of the immunosuppressive antibiotic agent 15-deoxyspergualin (DSG)
      on macrophages and autoreactive T helper lymphocytes from Lewis rats was analysed
      in vitro and in vivo. DSG did not inhibit antigen- or mitogen-induced
      proliferation of encephalitogenic or neuritogenic T helper cell lines in vitro.
      However, the presence of DSG during in vitro activation of the T cells strongly
      suppressed or completely abrogated their capacity to induce encephalitis (EAE) or
      neuritis (EAN) after adoptive transfer to naive rats, although expression of
      activation markers or adhesion molecules on the T line blasts was not down
      regulated by DSG. Like activation-induced T cell proliferation, IL-2-dependent
      growth of CD4+ T line cells was not affected by DSG. Preincubation of CD4+ T line
      cells in DSG during IL-2-driven proliferation for 48 h, however, inhibited the
      subsequent antigen- but not mitogen-induced activation of these T cells, although
      neither density of T cell receptors nor other surface molecules involved in
      antigen recognition were lowered on the cells exposed to DSG. Similar to its
      effect in vitro, in vivo administration of DSG for 10 days even at a
      concentration with cumulative toxicity did not suppress in vitro proliferation of
      spleen cells induced by mitogen or a mitogenic combination of anti-CD2
      antibodies. Furthermore, spleen cell and peripheral blood lymphocyte (PBL)
      surface antigens, particularly MHC molecules, were not altered by long-term
      treatment with DSG for 30 days. While there was a slight reduction in the number
      of polymorphonuclear cells in both populations, the proportion of the different
      leucocyte subpopulations remained unchanged. In contrast to the strong functional
      impact of DSG on autoreactive T helper cells, the drug did not inhibit the
      oxidative burst of macrophages or their MHC antigen expression. This study
      demonstrates a clear inhibitory effect of DSG on CD4+ T lymphocytes, but not
      macrophages. It provides an explanation for recent observations of a strong
      immunosuppressive in vivo effect of DSG on transplantation rejection and
      experimental autoimmune diseases, despite a normal mitogen response of T cells
      exposed to DSG in vivo and in vitro.

PMID- 7527747
TI  - Cytotoxic CD8+ T lymphocytes reactive with human immunodeficiency virus-1 produce
      granulocyte/macrophage colony-stimulating factor and variable amounts of
      interleukins 2, 3, and 4 following stimulation with the cognate epitope.
AB  - Infection with human immunodeficiency virus type 1 (HIV-1) induces vigorous and
      persistent cytotoxic CD8+ T cell responses. CTL clones were derived from
      peripheral blood or cerebrospinal fluid of three HIV-1 patients, with depressed
      CD4+ T cell counts. When stimulated with HLA-compatible target cells (B-LCL)
      presensitized with cognate HIV-1 peptides, all clones produced GM-CSF, TNF-alpha,
      and IFN-gamma and most produced low amounts of IL2, IL3, and IL4. After
      nonspecific stimulation with a phorbol ester and calcium ionophore, the clones
      secreted cytokines at levels similar to those from CD4+ lines from an HIV-1
      infected donor. The ability of supernatants from the stimulated CTL clones to
      support the formation of granulocyte-macrophage colonies in normal bone marrow
      suggests that the GM-CSF was biologically active. Release of cytokines by
      activated CTL may influence the immunopathogenesis of HIV disease.

PMID- 7527746
TI  - Flow cytometry analysis of OKT4 epitope deficiency in South African black
      children.
AB  - A case of OKT4 epitope deficiency referred for investigation with suspected
      immunodeficiency is described. Flow cytometry analysis of OKT4 epitope deficiency
      in a study group of healthy black children showed different manifestations of the
      lack of OKT4 epitope; a complete lack of OKT4+CD4+ peripheral blood lymphocytes
      (PBL) with normal numbers of OKT4A+ and Leu3a-CD4+ PBL, decreased percentage
      OKT4+CD4+ compared with OKT4A+ and Leu-3a+CD4+ PBL, decreased fluorescent
      staining intensity with OKT4 and a biphasic OKT4 staining pattern associated with
      a reduced OKT4/Leu-3a ratio. The percentage and fluorescent intensity of
      OKT4+CD4+ PBL in the study group were significantly lower (P < 0.0001) than Leu
      3a+CD4+ and OKT4A+CD4+ PBL. There is thus considerable risk of under-estimating
      the number of CD4+ cells in black South Africans if the OKT4 MoAb is used.

PMID- 7527748
TI  - IgM anti-A and D SnRNP proteins and IgM anti-dsDNA are closely associated in SLE
      sera.
AB  - U1RNP and Sm precipitins occur in systemic lupus erythematosus (SLE) and in
      overlap syndromes, while precipitins to Ro/SSA and La/SSB occur in SLE and its
      variants as well as Sjogren's syndrome. In studying IgM and IgG antibodies to
      these polypeptides by Western blot, we found the expected frequency of antibodies
      to the A protein of the U1RNP specificity and the D protein of the Sm specificity
      in sera with precipitins to U1RNP and Sm, but also found the frequent occurrence
      of both IgM and IgG anti-A and D in SLE sera with no precipitins, and in sera
      with anti-Ro/SSA and/or anti-La/SSB precipitins, but not in sera from patients
      with rheumatoid arthritis, polymyositis, scleroderma, or normals. We have studied
      the sera which bind the A and D polypeptides on Western blot to test their
      ability to bind native U1RNP (which contain the A and D proteins) in ELISA. The
      results indicate that most anti-Ro/SSA alone, anti-Ro/SSA, and anti-La/SSB sera
      as well as SLE sera with no precipitins react preferentially with the denatured A
      and D proteins. Further study of sera with IgM anti-A and D in Western blot
      reveals that these sera also frequently contain anti-double-stranded DNA
      antibodies. These results show that the anti-A and D responses, especially IgM
      anti-A and D, occur not only in patients with precipitating antibodies to SnRNPs,
      but in almost half of patients across the lupus spectrum. The extended prevalence
      of antibodies to the denatured A and D proteins in Western blot is associated
      with the cross-reaction of antibodies to dsDNA.

PMID- 7527750
TI  - [Relations between the external layers and the muscular mucosa of the colon. In
      situ electromyographic study in dogs].
AB  - From the oesophagus to the rectum, the muscularis mucosae comprises a thin layer
      of smooth muscle at the base of the digestive tract mucosa. Although the anatomic
      relations of the muscularis mucosae are well described, its physiological role is
      still only hypothesized. The muscularis mucosae could be implicated in the
      different functions of the digestive tract wall including absorption, secretion
      and protection. Modified function could be an early sign of certain pathological
      situations. The aim of this work was to investigate, in a dog model, the motor
      function of the muscularis mucosae by using an original technique for recording
      electromyograms and by comparing the electrical activity generated by the
      muscularis mucosae with the activity of the external muscle layers of the colon.
      We were able to demonstrate that in situ, the muscularis mucosae generates
      regular rhythmic electrical signals: slow wave patterns with rare episodes of
      rapid activity and sporadic action potentials. This rapid myoelectrical activity
      was not correlated with the much more intense activity of the external muscle
      layer responsible for the mechanical motor function of the colic wall. Finally,
      the motor activity of the muscularis mucosae appeared to be regulated and
      modulated by certain neurohormonal factors such as substance P.

PMID- 7527749
TI  - Integral membrane proteins associated with the nuclear lamina are novel
      autoimmune antigens of the nuclear envelope.
AB  - We have analyzed sera from 55 patients, most with rheumatic diseases, that all
      react with the nuclear envelope of human cells in immunofluorescence microscopy.
      The molecular targets of these autoantibodies were characterized by immunoblot
      analysis of fractions derived from rat liver nuclear envelopes. While numerous
      sera were found to react with previously characterized autoimmune antigens of the
      nuclear envelope including nuclear lamins and the pore complex glycoprotein
      gp210, a substantial number of the sera were found to recognize relatively minor
      integral membrane proteins of the nuclear envelope associated with the nuclear
      lamina (LAP 1A and LAP 2), which have not been previously identified as
      autoantigens. Autoantibodies to LAP 1A and LAP 2 are present in 9 and 29% of the
      patient sera, respectively. Only autoantibodies to lamins A/C were encountered
      more frequently (in 31% of the sera) than autoantibodies to LAP 2, suggesting
      that LAP 2 may be among one of the most prominent autoantigens of the nuclear
      envelope in rheumatic disease patients. Since recent studies have suggested that
      LAP 1A and LAP 2 may be involved in attaching lamins and chromosomes to the
      nuclear envelope, these findings could promoted understanding of nuclear envelope
      functions as well as autoimmunity.

PMID- 7527751
TI  - Chromosome sensitivity to bleomycin-induced mutagenesis in lymphocytes from
      colorectal cancer patients under 40 years of age.
AB  - PURPOSE: The incidence of colorectal cancer in young adults (under 40 years of
      age) is rare. The reason for the occurrence in these patients may lie in their
      genetic background. METHODS: We studied chromosomal fragility in peripheral blood
      lymphocytes of patients under the age of 40 with large bowel cancer. Lymphocytes
      from 24 subjects were examined: 10 untreated large bowel cancer patients under
      the age of 40 and 14 age-matched and sex-matched controls. RESULTS: The mean
      number of spontaneous chromosomal breaks per cells (b/c) was significantly higher
      in the right-sided large bowel cancer patients (0.23 +/- 0.12 b/c) compared with
      the control group (0.09 +/- 0.04 b/c; P < 0.01), but with no significant
      difference between the left-sided colorectal cancer patients and the control
      group. Lymphocytes exposed to the radiomimetic agent, bleomycin, were arrested in
      methaphase and analyzed for chromosome fragility. Mean chromosome breaks per cell
      in the left-sided colorectal cancer patients (1.60 +/- 0.49 b/c) were
      significantly higher than in either the controls (0.72 +/- 0.31 b/c; P < 0.001)
      or the right-sided, large bowel cancer patients (0.91 +/- 0.24 b/c; P < 0.05).
      CONCLUSIONS: The increased spontaneous chromosomal breaks in the right colon, as
      opposed to the increased mutagen-induced chromosomal breaks in the left colon,
      might indicate that in young colon cancer patients the occurrence of right-sided
      colon cancer is more likely to be genetically determined, whereas in left-sided
      colon cancer, environmental carcinogens might play a greater role.

PMID- 7527753
TI  - Complications of biliary stents in obstructive pancreatic malignancies. A case
      report and review.
AB  - Biliary stents have become a common palliative measure in the treatment of
      unresectable obstructive pancreatic cancer. Survival after endoscopic stenting
      rivals that of surgical bypass. Complications involving stents are not uncommon
      and can be categorized as related to placement, obstruction, migration, or
      fracture. A case report and review of stent-related morbidity is presented.
      Overall complication rates range from 15 to 34%, often requiring stent
      replacement and occasionally requiring surgical intervention.

PMID- 7527752
TI  - Trypsin activity. A new marker of acute alcoholic pancreatitis.
AB  - A normal serum amylase level is found in up to 32% of patients with acute
      alcoholic pancreatitis. This underlines the need for more sensitive diagnostic
      tests in this frequent cause of pancreatitis. Animal and human studies have shown
      that chronic alcohol consumption leads to important modifications in trypsinogen
      metabolism. The present work has prospectively analyzed admission serum trypsin
      activity with a new biochemical test and usual markers such as amylase, lipase,
      and immunoreactive trypsin in 32 attacks of acute pancreatitis. Seventeen were
      due to alcohol and 15 to other causes, including 11 with gallstone pancreatitis.
      High trypsin activity (median: 235 units/liter; range: 165-853) was found in all
      patients with acute alcoholic pancreatitis even when the amylase level was normal
      on admission (3/17: 18%). Trypsin activity did not differ between nonalcoholic
      pancreatitis (N = 15): 84 units/liter (42-98), alcoholic controls (N = 15): 77
      units/liter (40-122), and healthy controls (N = 62): 81 units/liter (15-143). The
      difference was not related to the severity of disease or circulating alpha 2
      macroglobulin, alpha 1-protease inhibitor, or immunoreactive trypsinogen levels.
      Lipase/amylase ratio was less discriminant than trypsin activity between
      alcoholic and nonalcoholic diseases. We conclude that serum trypsin activity
      seems specific to acute alcoholic pancreatitis and should be included in new
      prospective studies assessing biochemical testing of alcohol-related pancreatic
      diseases.

PMID- 7527754
TI  - Palliative treatment of malignant esophageal obstruction with metallic Wallstent.

PMID- 7527756
TI  - New uses for allopurinol.

PMID- 7527755
TI  - Potential therapeutics of vitamin E (tocopherol) in AIDS and HIV.

PMID- 7527759
TI  - Diuretic strategies in patients with renal failure.
AB  - A thorough understanding of the clinical pharmacology of diuretic agents,
      particularly loop diuretics, is crucial in patients with abnormal (and those with
      normal) renal function. Renal insufficiency represents a pathophysiological state
      characterised by diuretic resistance. Diuretic resistance is defined as a
      diminished pharmacological response, or diminished natriuresis, to a given dose
      of a diuretic. The phenomenon of diuretic resistance is demonstrated by a shift
      in the dose-response curve relating urinary diuretic excretion rates (dose) with
      sodium excretion (response). Pharmacokinetic factors underlie the diuretic
      resistance observed in patients with renal failure. Diminished renal blood flow
      and sodium filtration, accumulation of organic acids that inhibit tubular
      secretion of the diuretic, and inadequate cumulative sodium excretion to meet
      patients' needs contribute to the diuretic-resistant state. In contrast, the
      pharmacological response of remnant (i.e. remaining) nephrons to diuretic agents
      remains intact. The time course of delivery of diuretics to their intraluminal
      site of action is an independent determinant of natriuretic response. An
      administration regimen that continuously maintains effective rates of excretion
      of diuretics into the urine would be expected to cause a greater overall
      natriuretic effect than the same amount of diuretic administered in intermittent
      doses. Thus, diuretic administration strategies that take account of the altered
      pharmacological responses in patients with renal failure are necessary to provide
      effective and safe treatment. Additionally, such strategies warrant revision by
      the prescribing physician as renal function changes over time.

PMID- 7527758
TI  - Rational therapy of eating disorders.
AB  - Pharmacological treatments are one of several strategies used in the treatment of
      anorexia nervosa and bulimia nervosa. Many studies have found that
      antidepressants are effective in the treatment of bulimia nervosa and these drugs
      represent a mainstay of treatment for these patients. Over the past several
      years, selective serotonin reuptake inhibitors have become perhaps the most
      commonly used class of drugs. A variety of medications have been investigated for
      anorexia nervosa, but there is little consistent evidence that medications are
      effective. In both these illnesses it is important to diagnose and treat any
      comorbid conditions including mood and anxiety disorders; this may involve the
      administration of other medications, including anxiolytics such as
      benzodiazepines or buspirone or mood stabilising agents such as lithium, valproic
      acid (valproate sodium) or carbamazepine.

PMID- 7527761
TI  - Lansoprazole. A reappraisal of its pharmacodynamic and pharmacokinetic
      properties, and its therapeutic efficacy in acid-related disorders.
AB  - Lansoprazole is a benzimidazole derivative that effectively decreases gastric
      acid secretion, regardless of the primary stimulus, via inhibition of gastric
      H+,K(+)-adenosine triphosphatase (ATPase). It provides effective symptom relief
      and healing of peptic ulcer and reflux oesophagitis after 4 to 8 weeks of therapy
      and appears to prevent recurrence of lesions when administered as maintenance
      therapy. When administered at therapeutic dosages, lansoprazole produced higher
      healing rates than ranitidine or famotidine in patients with duodenal and gastric
      ulcers. Lansoprazole heals duodenal ulcers more rapidly than ranitidine or
      famotidine. Relief of ulcer symptoms in lansoprazole recipients is at least
      equivalent to, and tends to be more rapid than, that in patients receiving
      histamine H2-receptor antagonists. In comparisons with omeprazole 20 mg/day,
      lansoprazole 30 mg/day produced duodenal ulcer healing more rapidly and reduced
      ulcer pain to a greater extent at 2 weeks, but overall healing rates were similar
      after 4 weeks of therapy. At therapeutic dosages, lansoprazole produces superior
      healing and symptom relief of reflux oesophagitis in comparison with ranitidine,
      and it tends to relieve heartburn more effectively than omeprazole, although both
      agents produce equivalent healing. Healing of peptic ulcers or reflux
      oesophagitis refractory to histamine H2-receptor antagonists occurs after 8 weeks
      in the majority of patients treated with lansoprazole, and lansoprazole and
      omeprazole demonstrate similar efficacy in patients with refractory peptic
      ulcers. In patients with Zollinger-Ellison syndrome, lansoprazole effectively
      controls mean basal gastric acid output. Lansoprazole is generally well tolerated
      in clinical trials. The incidence of adverse effects is similar to that of
      omeprazole, ranitidine and famotidine in comparative studies. Combination therapy
      with lansoprazole and antibacterial agents such as amoxicillin, tinidazole,
      roxithromycin and/or metronidazole appears to eradicate Helicobacter pylori in 22
      to 80% of patients with this organism. Limited data also suggest that
      lansoprazole may have superior activity against H. pylori in comparison with
      omeprazole, although the clinical relevance of this preliminary finding requires
      further confirmation. Thus, lansoprazole may be considered as alternative to
      existing antisecretory agents available for the treatment of acid-related
      disorders, particularly because it may provide more rapid healing and relief of
      symptoms.

PMID- 7527760
TI  - Porcine-derived lung surfactant. A review of the therapeutic efficacy and
      clinical tolerability of a natural surfactant preparation (Curosurf) in neonatal
      respiratory distress syndrome.
AB  - Porcine-derived lung surfactant (PLS; Curosurf) has shown efficacy in neonatal
      respiratory distress syndrome. PLS consists of phospholipids, mainly
      dipalmitoylphosphatidylcholine, the primary surface-active agent of natural lung
      surfactant, and pulmonary surfactant-associated proteins which facilitate
      spreading and adsorption of the surface-active agent at the air-alveolar
      interface. Intratracheal administration of a single dose of PLS 200 mg/kg
      significantly improves the survival rate and reduces the incidence of
      bronchopulmonary dysplasia at 28 days in premature infants (birthweight 700 to
      2000g) with severe respiratory distress syndrome (fraction of inspired oxygen >
      or = 0.60). PLS also reduces the incidence of air leak events such as pulmonary
      interstitial emphysema and pneumothorax. The response rate may be further
      improved by administration of additional 100 mg/kg doses at 12-hour intervals to
      infants showing a poor response or relapse after a single dose. PLS prophylaxis
      reduces the incidence and severity of respiratory distress syndrome in premature
      infants at high risk of developing the disease; however, it remains unclear
      whether the eventual clinical outcome is similar or superior to that observed in
      infants who receive rescue treatment. PLS is well tolerated and does not appear
      to increase the incidence of complications of prematurity or respiratory distress
      syndrome, including patent ductus arteriosus and intraventricular haemorrhage.
      Although its effect on long term development require further investigation, early
      indications are that PLS is not associated with any long term adverse sequelae.
      Comparative trials are clearly warranted to determine the efficacy and
      tolerability of PLS relative to that of other available surfactant preparations,
      particularly to explore preliminary indications that a more rapid effect of
      natural surfactants such as PLS (compared with synthetic products) may correlate
      with improved clinical outcomes, and that PLS may result in fewer complications
      than synthetic preparations. Thus, available data show PLS to be a very effective
      agent for the treatment and prophylaxis of neonatal respiratory distress
      syndrome, and that it may have some advantages over synthetic preparations.

PMID- 7527757
TI  - The treatment of atrial fibrillation. An evaluation of drug therapy, electrical
      modalities and therapeutic considerations.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in
      clinical practice, and is responsible for considerable morbidity. Basic studies
      have shown that AF is usually due to the coexistence of multiple functional
      atrial re-entry circuits, and that the main determinant of its haemodynamic
      manifestations is the ventricular response rate. The major adverse clinical
      consequences of AF include palpitations, impaired cardiac function and
      thromboembolism. One approach to treating AF is to convert the patient's cardiac
      rhythm to sinus rhythm by direct current electrical cardioversion, which is
      initially successful in about 90% of cases. However, the AF recurrence rate over
      the year subsequent to cardioversion is very high, in the order of 75% in
      patients receiving no drug therapy. Class I and class III antiarrhythmic drugs
      reduce the rate of recurrence of AF, but at the expense of a variety of potential
      adverse effects including ventricular proarrhythmia. The latter is a rare effect
      (occurring in 1 to 2% of patients receiving most drugs), but can be lethal. A
      second approach to therapy is to leave the patient in AF, but to control the
      ventricular response rate and to prevent thromboemboli with oral anticoagulants.
      Disadvantages of this approach include the possibilities of functional
      limitations imposed by the arrhythmia, adverse effects of drug therapy, and major
      bleeding related to anticoagulation. New approaches currently under study include
      surgery to prevent AF from sustaining itself, implantable cardioverter devices to
      maintain sinus rhythm, and modification of AV nodal function by the induction of
      controlled radiofrequency injury.

PMID- 7527762
TI  - Nimesulide. An update of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic efficacy.
AB  - Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) administered orally
      or rectally twice daily for a variety of inflammatory and pain states. In mostly
      short term studies (up to 4 weeks), it was effective in reducing pain associated
      with osteoarthritis, cancer, thrombophlebitis, oral surgery and dysmenorrhoea in
      adults, reducing pain associated with general surgery in adults and children, and
      pain, fever and inflammation accompanying respiratory tract infections,
      otorhinolaryngological diseases and traumatic injury in adults and children.
      Nimesulide appeared to be at least as effective as other NSAIDs in all of these
      indications. Nimesulide has been well tolerated by adult, elderly and paediatric
      patients in clinical trials and large postmarketing surveillance studies. In
      general qualitative terms nimesulide exhibits the usual adverse events associated
      with NSAIDs (gastrointestinal, dermatological and neurological). However, it has
      a pharmacodynamic profile suggestive of a possibly reduced propensity to cause
      adverse gastrointestinal effects, although this has not been conclusively
      demonstrated in comparative clinical trials, many of which showed a similar
      incidence of such effects for nimesulide and the comparator agent. Additionally,
      nimesulide has been well tolerated by most aspirin (acetylsalicylic acid)- and/or
      NSAID-intolerant patients and in patients with asthma. Thus, available evidence
      indicates that nimesulide is an effective and well tolerated alternative to other
      NSAIDs in the short term treatment of pain and inflammation of osteoarthritis and
      various other causes.

PMID- 7527764
TI  - Comparison of visual evoked potentials elicited by light-emitting diodes and TV
      monitor stimulation in patients with multiple sclerosis and potentially related
      conditions.
AB  - Visual evoked potentials elicited by reversal of a checkerboard pattern
      constructed of square, red light-emitting diodes (LEDs) were compared with a
      conventional black and white pattern displayed on a TV monitor in control
      subjects and in 71 patients with established or suspected multiple sclerosis.
      Both stimuli elicited distinct responses in the control groups: the latencies
      were longer with LED stimulation while the amplitudes of the various components
      were differently altered. The frequency of abnormal responses among the patients
      was higher with LED stimulation than with TV stimulation, but the highest
      diagnostic yield was obtained when both methods were combined.

PMID- 7527765
TI  - Use of pattern electroretinography to differentiate acute optic neuritis from
      acute anterior ischemic optic neuropathy.
AB  - The transient pattern electroretinogram (PERG) was recorded from 16 patients with
      acute optic neuritis and from 13 patients with acute non-arteritic anterior
      ischemic optic neuropathy (AION). All patients were tested within 35 days from
      the the onset of visual symptoms and all had significant central visual field
      abnormalities in their affected eyes as quantified by automated perimetry.
      Analysis of the PERGs showed that the amplitude of the N95 peak was abnormally
      reduced for each eye affected with AION while it remained normal in optic
      neuritis. No significant alteration in P50 amplitude was observed in either
      condition. The loss of N95 amplitude in AION was highly correlated with the
      average depth of visual field loss (in decibels) within a radius of 10 degrees of
      fixation. These results suggest that PERG could be used early in the course of
      optic neuropathy to distinguish optic neuritis from AION in those cases for which
      the diagnosis is still uncertain after the clinical examination.

PMID- 7527766
TI  - Covariability of visually evoked potentials and simple motor reaction times.
AB  - Visually evoked potentials (VEPs) were recorded during simple motor reaction time
      (RT) experiments using spatially localized, contrast modulated visual stimuli.
      VEPs were averaged in groups, called "subensembles," depending on the speed of
      the subject's motor response. To a specific visual stimulus, the VEP response
      time of a subensemble covaries with motor response latency according to the same
      linear relationship found to describe conventionally averaged VEPs and RTs over a
      wide range of stimuli.

PMID- 7527763
TI  - Ganciclovir. An update of its therapeutic use in cytomegalovirus infection.
AB  - The antiviral nucleoside analogue ganciclovir has demonstrated in vitro activity
      against human cytomegalovirus and effectively treats infection caused by this
      organism in various immunocompromised patient groups. The drug prolongs time to
      progression in patients with acquired immune deficiency syndrome (AIDS)-related
      cytomegalovirus retinitis although life-long maintenance therapy is required.
      Direct comparisons between ganciclovir and foscarnet in this indication are few;
      nevertheless, the 2 drugs appear to have equal therapeutic efficacy in treating
      cytomegalovirus retinitis although results from 1 study in this indication
      suggest that foscarnet has an advantage in terms of patient survival. AIDS
      related gastrointestinal and, to a lesser extent, pulmonary cytomegalovirus
      infection also respond to treatment with ganciclovir; maintenance therapy does
      not appear to be required in these latter 2 indications. Ganciclovir is also
      useful against cytomegalovirus infection in organ transplant recipients. The drug
      is most effective when given prophylactically or as early treatment for
      asymptomatic infection in bone marrow transplant recipients; treatment of
      established infection is less effective in this patient group. However,
      established infection in solid organ transplant recipients appears to respond to
      treatment with ganciclovir. The most common adverse event during ganciclovir
      therapy is haematological toxicity but this appears to be readily reversible on
      discontinuation of the drug. In addition, coadministration of granulocyte colony
      stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF) has been shown
      to prevent ganciclovir-associated neutropenia. Thus, ganciclovir is a valuable
      treatment for cytomegalovirus infection in patients with AIDS and in organ
      transplant recipients. Further studies comparing ganciclovir and foscarnet
      ideally incorporating the use of G-CSF or GM-CSF to prevent ganciclovir
      associated neutropenia and assessing survival as 1 endpoint--should further
      clarify the relative role of ganciclovir as treatment or prophylaxis for
      cytomegalovirus infection.

PMID- 7527770
TI  - The effects of stimulus rates upon median, ulnar and radial nerve somatosensory
      evoked potentials.
AB  - We examined the effect of stimulus rates on the somatosensory evoked potential
      (SEP) amplitude following stimulation of the median nerve (MN) and the ulnar
      nerve (UN) at the elbow or wrist, and the radial nerve (RN) at the wrist in 12
      normal subjects. We measured the amplitude of frontal (P14-N18-P22-N30) and
      parietal peaks (P14-N20-P26-N34) at a stimulus rate of 1.1, 3.5 and 5.7 Hz. The
      amplitude attenuation was found at frontal P22 and N30 and to a lesser degree at
      parietal N20 and P26 peaks with an increasing stimulus rate from 1.1 to 5.7 Hz.
      The amplitude attenuation was greatest at the elbow when compared to the wrist
      stimulation for both MN and UN. The attenuation was least for wrist stimulation
      for the RN. The UN block by local anesthesia just distal to the stimulus
      electrode at the elbow abolished the amplitude attenuation caused by the fast
      stimulus rate. The observed amplitude attenuation with the faster stimulus rate
      is probably due, in part, to interference from the "secondary" afferent inputs.
      The secondary afferent inputs arise from peripheral receptor stimulation (muscle,
      joint and/or cutaneous) as a subsequent effect of efferent volleys initiated from
      the point of stimulation. The greater number of peripheral receptors being
      activated as more proximal sites of stimulation in a mixed nerve would result in
      greater attenuation of the SEP recorded from scalp electrodes. We postulate that
      the attenuation of frontal peaks by the fast stimulus rate is due to the frontal
      projection of interfering "secondary" afferent inputs.

PMID- 7527767
TI  - Somatosensory evoked potentials at rest and during movement in Parkinson's
      disease: evidence for a specific apomorphine effect on the frontal N30 wave.
AB  - Studies attempting to relate the abnormalities of the frontal N30 components of
      the somatosensory evoked potentials (SEPs) to motor symptoms in Parkinson's
      disease (PD) have shown contradictory results. We recorded the frontal and
      parietal SEPs to median nerve stimulation in 2 groups of PD patients: a group of
      17 patients presenting the wearing-off phenomenon, and a group of 10 untreated PD
      patients. The results were compared with a group of 13 healthy volunteers of the
      same age and with a group of 10 non-parkinsonian patients. All parkinsonian and
      non-parkinsonian patients were studied before ("off" condition) and after a
      subcutaneous injection of apomorphine ("on" condition). The gating effects of a
      voluntary movement (clenching of the hand) on the SEPs were also studied for the
      wearing-off group of PD patients (in states off and on) in comparison with the
      healthy subjects. At rest and in the off condition the amplitude of the frontal
      N30 was significantly reduced in the 2 groups of PD patients. We demonstrate that
      the movement gating ability of the PD patient is preserved in spite of the
      reduced amplitude of the frontal N30. This result suggests that the specific
      change in the frontal N30 in PD is not the consequence of a continuous gating of
      the sensory inflow by a motor corollary discharge. Clinical motor improvement
      induced by apomorphine was associated with a significant enhancement of the
      frontal N30 wave. In contrast, the subcortical P14 and N18 waves and the cortical
      N20, P22, P27 and N45 were not statistically modified by the drug. Apomorphine
      infusion did not change the absolute reduced voltage of the N30 reached during
      the movement gating. While the frontal N30 component of the non-parkinsonian
      patients was significantly lower in comparison to healthy subjects, this wave did
      not change after the apomorphine administration. In the wearing-off PD patient
      group the frontal N30 increment was positively correlated with the number of off
      hours per day. This specific apomorphine sensitivity of the frontal N30 was
      interpreted as a physiological index of the dopaminergic modulatory control
      exerted on the neuronal structures implicated in the generation of the frontal
      N30.

PMID- 7527768
TI  - The role of upper limb somatosensory evoked potentials in the management of
      cervical spondylotic myelopathy: preliminary data.
AB  - We studied upper limb somatosensory evoked potentials (SEPs) in 11 patients with
      MRI and clinical evidence of cervical spondylotic myelopathy (CSM), before and
      after cervical open-door laminoplasty. SEP studies before surgery revealed two
      main types of abnormality, the first characterized by the isolated loss of the
      spinal N13 response, reflecting the dysfunction of dorsal horn cervical cells in
      4 patients. The second combined abnormalities of both spinal N13 and scalp far
      field P14 potential, suggesting the involvement of both dorsal horn cells and
      dorsal columns at the cervical level in 7 patients. After surgery, N13 recovered
      in 9 patients, while P14 abnormalities remained unchanged. Clinical recovery,
      evaluated by means of the Japanese Orthopaedic Association (JOA) disability
      scale, was accompanied by SEP improvement. Moreover, this improvement was more
      pronounced in patients with isolated loss of the N13 than in patients with
      combined abnormalities of the N13 and scalp P14 response. Our data strongly
      suggest that upper limb SEPs can be useful in monitoring the effectiveness of
      surgery, as well as in selecting before surgery patients who are likely to have a
      better postsurgical outcome.

PMID- 7527771
TI  - Effect of manipulation and fractionated finger movements on subcortical sensory
      activity in man.
AB  - Previous studies have shown that the somatosensory evoked potentials (SEPs)
      recorded from the scalp are modified or gated during motor activity in man.
      Animal studies show corticospinal tract terminals in afferent relays, viz. dorsal
      horn of spinal cord, dorsal column nuclei and thalamus. Is the attenuation of the
      SEP during movement the result of gating in subcortical nuclei? This study has
      investigated the effect of manipulation and fractionated finger movements of the
      hand on the subcortically generated short latency SEPs in 9 healthy subjects.
      Left median nerve SEPs were recorded with electrodes optimally placed to record
      subcortical activity with the least degree of contamination. There was no
      statistically significant change in amplitude or latency of the P9, N11, N13,
      P14, N18 and N20 potentials during rest or voluntary movement of the fingers of
      the left hand or manipulation of objects placed in the hand. The shape of the N13
      wave form was not modified during these 3 conditions. It is concluded that in man
      attenuation of cortical waves during manipulation is not due to an effect of
      gating in the subcortical sensory relay nuclei.

PMID- 7527769
TI  - Comparison of somatosensory evoked fields to airpuff and electric stimuli.
AB  - We recorded somatosensory evoked magnetic fields (SEFs) from 6 healthy subjects
      with a 122-channel whole-scalp SQUID gradiometer. In separate experiments,
      airpuff stimuli were delivered to the dorsum of the proximal phalanx of the
      middle finger, and electric stimuli were delivered to the median nerve at the
      wrist; the interstimulus interval was 3 sec and left and right hands were
      stimulated in subsequent sessions. Airpuffs evoked clear and reproducible
      responses in all subjects. First responses were recorded over the SI cortex. All
      subjects showed SII responses both to contra- and ipsilateral airpuffs. The
      posterior parietal source, identified previously to electric stimulation, was
      activated also by airpuffs, but only in the right hemisphere. The earliest
      responses from SI were smaller in amplitude and longer in latency to airpuffs
      than to electric stimuli; the long-latency responses arising from the other
      somatosensory areas did not differ significantly.

PMID- 7527776
TI  - Measurement of interleukin-1 stimulated constitutive prostaglandin G/H synthase
      (cyclooxygenase) mRNA levels in osteoblastic MC3T3-E1 cells using competitive
      reverse transcriptase polymerase chain reaction.
AB  - To assess regulation of constitutive prostaglandin G/H synthase (PGHS-1) by
      interleukin-1 (IL-1) in osteoblastic MC3T3-E1 cells, we compared analysis by
      competitive reverse transcriptase-polymerase chain reaction (RT-PCR) with
      Northern blot analysis. Using RT-PCR, IL-1 increased PGHS-1 mRNA levels by 1.84
      +/- 0.10 or 2.07 +/- 0.17, depending on the method of calculation. Using Northern
      blot analysis, the effect of IL-1 on PGHS-1 mRNA levels was more variable, and
      the variability was increased by normalization of PGHS-1 mRNA levels to the
      housekeeping genes, beta-actin and glyceraldehyde phosphate dehydrogenase
      (GAPDH), because their mRNA levels were also regulated by IL-1. We conclude that
      competitive RT-PCR is a reproducible and accurate method for studying small
      changes in mRNA levels.

PMID- 7527772
TI  - The auditory P50 response is normal in Alzheimer's disease when measured via a
      paired click paradigm.
AB  - Recent findings of missing or markedly attenuated P50 (or P1) auditory ERPs in
      Alzheimer's disease (AD) patients suggest this may be a useful diagnostic and/or
      prognostic marker of AD cholinergic deficits. Those studies used repetitive 1/sec
      clicks. Given P50's long recovery time, all but the first click in that paradigm
      was presented during the recovery of the P50 generation system from the response
      to the prior click. We studied 8 AD patients and 17 elderly controls using a
      paradigm incorporating 7-8 sec intervals between clicks, which allows examination
      of P50 generation separate from P50 recovery. With the long inter-click interval,
      we identified P50 responses in most AD patients and controls, and found no
      difference in P50 amplitude between groups. These results suggest that if there
      is a P50 deficit in AD patients, it is the result of the accumulative effect of
      repetitive stimulation, rather than a primary deficit in P50 generation.

PMID- 7527773
TI  - ERPs in schizophrenic patients during word recognition task and reaction times.
AB  - Event-related brain potentials (ERPs) were recorded in 28 schizophrenic patients
      and 26 healthy controls during a word recognition task. In each trial, stimuli
      consisting of S1 (word) and S2 (word or non-word) were presented. The subjects
      were required to indicate whether S2 was a word or a non-word by pressing
      buttons. For both groups, a clear N370 was elicited by S2 which were non-word or
      semantically unrelated to its S1. The N370 amplitude did not differ between the
      groups. The schizophrenics responded more slowly than the controls, and the
      latencies of P200 and N370 were longer for patients than for controls. However,
      these latencies did not differ between the groups when their reaction times were
      matched.

PMID- 7527775
TI  - Prognostic value of frontal and parietal somatosensory evoked potentials in
      severe head injury: a long-term follow-up study.
AB  - We have shown that the combined analysis of the frontal and parietal
      somatosensory evoked response (SEP) improves the global short-term outcome
      prediction in severe head injury (SHI) after 3-6 months. In the present study the
      same patients were reexamined 18 months after trauma and the prognostic value of
      the combined SEP parameters reassessed, in particular their value of predicting
      the exact Glasgow Outcome Scale (GOS) class reached (as opposed to a crude good
      or bad distinction). Frontal (P20/22, N30) and parietal (N20) SEP components were
      studied in 50 patients within 72 h after the injury and were related to the GOS
      after 3-6 months and again after 18 months. When both frontal and parietal
      components were used as predictors, discriminant analysis correctly classified
      76% of the patients after 3-6 months and 82% after 18 months. Considering
      parietal SEP alone, classification was less accurate (74% after 3-6 months, and
      68% after 18 months) and misclassifications were more severe. Our results show
      that (i) a combined analysis of frontal and parietal components of the SEP
      improves and refines the outcome prediction in SHI, (ii) the predictive power of
      the combined approach increases with time after trauma, while that of the
      parietal response alone decreases.

PMID- 7527777
TI  - Staurosporine can inhibit the G1-S transition induced by a calcium channel
      agonist by blocking the pathway independent of phorbol ester-sensitive protein
      kinase C in rat thyroid cells (FRTL-5).
AB  - IGF-I, when added to TSH-primed FRTL-5 cells, can induce a long lasting Ca2+
      influx followed by the DNA synthesis. BAY K8644, a Ca2+ channel agonist, can also
      induce the DNA synthesis in TSH-treated cells. Staurosporine, which is known to
      be a potent inhibitor of protein kinase C(PKC) strongly inhibited the DNA
      synthesis caused by these two reagents. However, in PKC-down regulated cells, IGF
      I and BAY K8644 could also evoke the DNA synthesis and the inhibitory effect of
      staurosporine persisted. These inhibitory effects did not relay on inhibition of
      the Ca2+ influx induced by BAY K8644. Thus these results demonstrate that
      staurosporine acts at a point distal to Ca2+ influx to inhibit G1-S transition
      and this staurosporine-sensitive pathway possibly mediates the mitogenic signal
      in PKC-independent manner.

PMID- 7527774
TI  - P3 latency jitter assessed using 2 techniques. II. Surface and sphenoidal
      recordings in subjects with focal epilepsy.
AB  - We compared the latency variability in auditory P3s of 13 subjects with
      unilateral temporal lobe epilepsy (TLE) to that of normal controls. We predicted
      that increased latency jitter would occur in TLE subjects, particularly on the
      epileptic side. ERPs were recorded from scalp and sphenoidal sites relative to a
      balanced non-cephalic reference. Signal-to-noise ratios (SNRs) were calculated
      for each subject. Data were excluded if SNRs fell below 0.4. P3 latency jitter
      was estimated using 2 methods: Woody's algorithm and the maximum likelihood
      technique (MLT), a novel method of jitter assessment. SNRs were significantly
      higher in controls and were maximal posteriorly for both groups. P3 peak
      amplitude was significantly smaller in TLE subjects at temporal sites. Latency
      jitter (MLT method) was greatest in posterior sites and mirrored the jitter
      profiles of controls. Latency jitter was significantly higher in TLE subjects in
      bilateral frontal and temporal sites, but was not higher on the side of the focus
      and could not be attributed to lower SNRs. The increased bilateral latency jitter
      in these patients may be related to effects of anticonvulsants or the more
      extensive nature of the underlying epileptic disorder.

PMID- 7527778
TI  - The possible involvement of galanin in the modulation of the function of rat
      pituitary-adrenocortical axis under basal and stressful conditions.
AB  - The effect of a s.c. bolus injection of 2 micrograms galanin on the hypothalamo
      pituitary-adrenocortical (HPA) axis were investigated in both normal and ether
      stressed (2 min ether-vapor inhalation) or cold-stressed (20 min at 4 degrees C)
      rats. Blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B)
      were measured by specific RIA, 1, 2 or 4 h after galanin injection. Galanin
      administration to normal rats resulted in a marked rise in the blood levels of
      ACTH, ALDO and B at 1h and 2 h, the values returned to the baseline after 4 h.
      Ether and cold stresses notably raised the blood levels of ACTH, ALDO and B, and
      these rises lasted unchanged until 4 h. Galanin markedly potentiated ACTH and
      ALDO responses to ether stress at 1 and 2 h, but B response remained unchanged.
      ACTH response to cold stress was not affected by galanin; however, galanin
      magnified ALDO response to cold stress at 4 h, and enhanced at 1 h and depressed
      at 2 h that of B. In light of these findings the following conclusions can be
      drawn: (i) galanin exerts a stimulatory effect on HPA axis of rats under basal
      conditions; (ii) under our experimental conditions, ether stress exerts a
      stronger stimulation of HPA axis than cold stress; (iii) the galaninergic
      mechanisms involved in the stimulation of ACTH release do not interfere with
      ether stress-activated ones controlling ACTH secretion, and are probably similar
      to those underlying the effect of cold stress; (iv) steroidogenic capacity of
      adrenal cortex, at least in term of glucocorticoid hormones, is a rate-limiting
      step in the response of rat HPA axis to severe stresses; and (v) galanin exerts a
      direct secretory action of the rat adrenal gland, that can manifest itself only
      in the case of submaximally cold stress-stimulated HPA axis.

PMID- 7527779
TI  - Technetium-99m sestamibi: an indicator of breast cancer invasiveness.
AB  - As recently shown, angiogenesis is the most reliable marker of breast cancer
      invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue
      specimens. We have used technetium-99m sestamibi, a marker of regional blood flow
      in other organs that often but not always images breast cancer, to assess the
      invasiveness of this tumour. Nineteen patients, ten with nodal metastases and
      nine without any metastases, were studied with 99mTc-sestamibi scintigraphy
      before operation. Angiogenesis was quantitatively assessed by immunohistochemical
      staining of endothelia for factor VIII. All the node-positive (N+) patients at
      surgical revision showed a positive 99mTc-sestamibi scan of the primary tumour
      and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive
      tumours showed more than 135 microvessels/mm2 and one showed 99 microvessels/mm2;
      by contrast there were 71.6 +/- 12.1 microvessels/mm2 in the nine N- and
      sestamibi-negative tumours. Our study suggests that 99mTc-sestamibi is a marker
      of breast cancer invasiveness: its uptake is related to angiogenesis and,
      possibly, to oxidative metabolism of the tumour.

PMID- 7527780
TI  - The prevalence of hepatitis B and C in an antenatal population of various ethnic
      origins.
AB  - A total of 3522 samples of serum, collected anonymously from women attending an
      antenatal clinic, was tested for hepatitis B surface antigen and antibody to
      hepatitis C. The prevalence of anti-HCV was low; only five confirmed positives
      were found (0.14%). The prevalence of hepatitis B overall was 0.56%, but was
      1.04% in women from immigrant groups. Hepatitis B carriage is therefore four
      times more common than hepatitis C carriage in the antenatal population comprised
      of various ethnic origins. The patterns of infection in the two viruses are
      reversed, hepatitis B being more common in Asian, S.E. Asian and West Indian
      mothers and hepatitis C being more common in mothers of white Caucasian origin.
      Routine antenatal screening for anti-HCV is discussed.

PMID- 7527782
TI  - c-kit protein (stem cell factor receptor) expression on cells with erythroid
      characteristics and on normal human bone marrow without the use of monoclonal
      antibodies.
AB  - Stem cell factor (SCF) is a determining and crucial element in the development of
      early hematopoietic cells. The SCF receptor protein has been identified as the
      product of the protooncogene c-kit and has been detected using monoclonal
      antibodies (MAbs) on a broad selection of erythroid, myeloid, and lymphoid cell
      lines as well as on bone marrow mononuclear cells (BMMNC). SCF is known to
      increase both the number and size of burst-forming unit-erythroid (BFU-E)
      colonies in normal human BM culture in a dose-dependent fashion. A detailed study
      of the involvement of SCF and its receptor c-kit in normal erythropoiesis will
      help elucidate intrinsic irregularities of anemias such as Diamond Blackfan
      Anemia, an aregenerative congenital anemia. Abnormalities of this heterogeneous
      disorder are confined to the red cell lineage and are thought to arise through a
      defect at the stem/progenitor cell level. Our in vitro studies suggest that SCF
      therapy will influence BFU-E production in at least a portion of these patients,
      although in another group, SCF response is limited or absent. Additionally,
      further investigations have shown a possible c-kit signaling defect that clearly
      necessitates further c-kit characterization. To parallel this, we, therefore,
      attempted to study the relationship of c-kit with its ligand. This report
      describes a nonradioactive method for detecting SCF receptors that varies from
      conventional assays in that the fluorescent label conjugated to the SCF/c-kit
      complex is connected via an extended-ester linkage that reduces steric influence
      and promotes full normal structural ligand binding of the SCF to its
      receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527781
TI  - Hepatitis C virus infection in Iceland: a recently introduced blood-borne
      disease.
AB  - This study demonstrates a very high prevalence of antibodies to hepatitis C virus
      among Icelandic intravenous (i.v.) drug users. Of 152 identified i.v. drug users
      95 (63%) were shown to have antibodies to the hepatitis C virus. In contrast the
      seroprevalence in the general Icelandic population is low, (0.2%). Almost all
      cases of hepatitis C virus infection in Iceland are due to i.v. drug use or to
      use of infected blood or blood products. Sporadic cases with unexplained modes of
      transmission, a significant portion of hepatitis C infections elsewhere, are
      virtually non-existent in Iceland. The results of this study are consistent with
      the hypothesis that the sporadic community-acquired cases could be caused by
      blood transfer due to bites from insect vectors such as mosquitoes which are not
      found in Iceland.

PMID- 7527783
TI  - Ultrastructural localization of stem cell factor in canine marrow-derived stromal
      cells.
AB  - Stromal cell lines derived from canine long-term bone marrow cultures (LTBMC)
      were characterized regarding the expression of growth factors and especially the
      localization of stem cell factor (SCF) (c-kit ligand). One cell line (DO64) was
      immortalized by transformation with a retroviral vector containing the open
      reading frames (ORFs) E6 and E7 of the human papilloma virus type 16 (HPV-16).
      Transfection did not change cellular characteristics but rendered the cell line
      more independent from culture conditions. The transformed line DO64 consisted
      mainly of fibroblast-like cells. In addition, some cells showed endothelial and
      some smooth-muscle cell features. Stromal cells expressed a broad spectrum of
      surface markers, including low levels of major histocompatibility-complex (MHC)
      class-II antigens. A new murine monoclonal antibody (MAb), RG7.6 (IgG1), specific
      for canine SCF, recognized the majority of fibroblast-like stromal cells. The
      staining pattern for SCF showed perinuclear and intracytoplasmic dense areas.
      Immunoelectron microscopy revealed the localization of SCF in secretory vesicles,
      the perivesicular cytoplasm, and bound to the cytoplasmatic membrane. RNA
      analysis showed that stromal cells transcribed, in addition to SCF, messages for
      granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte CSF (GM-CSF),
      interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta). In summary,
      we have established and characterized canine marrow-derived stromal cell lines,
      and using the new MAb RG7.6, we have localized SCF to cytoplasmatic vesicles as
      well as the membrane of stromal cells.

PMID- 7527785
TI  - Bovine fetal-liver stromal cells support erythroid colony formation: enhancement
      by insulin-like growth factor II.
AB  - Stromal cells are one of the components of the hematopoietic microenvironment,
      which is crucial for the proliferation and differentiation of hematopoietic
      cells. We have obtained a bovine fetal-liver stromal cell line that supports
      erythroid colony formation in the presence of erythropoietin. The cells are
      cytokeratin-negative and vimentin-positive, indicating a mesenchymal origin.
      Furthermore, they have phagocytic activity and show endothelial-like morphology.
      Erythropoietin at a concentration of 2 mU/mL was sufficient to increase
      erythropoiesis in the presence of these stromal cells, and the effect could be
      further enhanced in the presence of physiological concentrations of insulin-like
      growth factor II. The supportive role of stromal cells on erythroid colony
      formation could still be observed, although to a lesser extent, when the
      erythroid precursors were physically separated from the stromal monolayer by an
      agar layer or with serum-free media conditioned by stromal cells. Ultrafiltration
      of the conditioned media indicated that the active factors have a nominal
      molecular weight smaller than 3 kD, which does not correspond to any of the known
      cytokines with erythroid-cell stimulating activities. Our data suggest that these
      fetal-liver stromal cells play an important role in fetal erythropoiesis, a
      function which was previously thought to be played exclusively by fetal
      hepatocytes.

PMID- 7527784
TI  - Inhibition of attachment between cultured mast cells and fibroblasts by phorbol
      12-myristate 13-acetate and stem cell factor.
AB  - Cultured mast cells (CMC) derived from the bone marrow of mice express the
      receptor encoded by the W (c-kit) locus (W receptor), and the WCB6F1(+/+)-3T3
      fibroblasts express the ligand encoded by the Sl locus (stem cell factor [SCF]).
      CMC attach to the fibroblasts through the W receptors and cell-bound SCF. We
      investigated the effect of phorbol 12-myristate 13-acetate (PMA) and recombinant
      murine SCF (rmSCF) on the attachment. PMA induced both the internalization and
      shedding of W receptors, whereas rmSCF induced only the internalization.
      Moreover, both PMA and rmSCF reduced the expression of c-kit mRNA levels in CMC.
      Addition of either PMA or rmSCF to the coculture of CMC and fibroblasts resulted
      in the inhibition of attachment. Since the magnitude of the attachment between
      CMC and fibroblasts may be manipulated by changing the doses of either PMA or
      rmSCF, the present experimental system may be useful as a model for the
      attachment between blood cells and stromal cells.

PMID- 7527786
TI  - Relationship of infused CFU-GM and CFU-Mk mobilized by chemotherapy with or
      without G-CSF to platelet recovery after autologous blood stem cell
      transplantation.
AB  - Although hematologic reconstitution is usually rapid after autologous blood stem
      cell transplantation (ABSCT), there is an occasional delay in platelet recovery.
      We studied the hematologic recovery of 27 adult patients with hematologic
      malignancies who received marrow-ablative chemotherapy and ABSCT to determine
      whether or not the numbers of infused mononuclear cells (MNC), colony-forming
      units granulocyte/macrophage (CFU-GM), and colony-forming units megakaryocyte
      (CFU-Mk) were related to the speed of platelet recovery after ABSCT. Peripheral
      blood stem cells were collected using chemotherapy-induced mobilization with or
      without cytokine therapy. While the number of MNC infused did not show a
      significant correlation with time to platelet recovery as well as granulocyte and
      reticulocyte recovery, the logarithmic number of CFU-GM-infused did (p < 0.01).
      We also found a significant correlation between the logarithmic number of CFU-Mk
      infused and the time to platelet recovery (p < 0.01). These findings suggest that
      the number of CFU-GM-infused is a reliable indicator of hematopoietic recovery
      and that the number of CFU-Mk-infused is no more reliable than CFU-GM for
      predicting platelet recovery after ABSCT.

PMID- 7527788
TI  - Basic principles of radiotherapy for surgical oncologists. 6--Patient selection.

PMID- 7527787
TI  - Circulating cell adhesion molecules in bronchial lavage and serum in COPD
      patients with chronic bronchitis.
AB  - The initial phase of inflammation in bronchial asthma appears to be triggered by
      the expression of leucocyte-endothelial adhesion molecules on endothelial cell
      surfaces. Cell adhesion molecules (CAMs) cause adhesion of leucocytes to the
      endothelium prior to their subsequent extravasation into inflamed tissue. We
      wanted to determine whether circulating intercellular adhesion molecule-1 (cICAM
      1) and circulating E-selectin (cE-selectin) could be detected in bronchial lavage
      fluid and serum in patients with stable chronic obstructive pulmonary disease
      (COPD) and chronic bronchitis. Bronchoscopy and small volume bronchial lavage was
      performed in 19 patients with COPD and chronic bronchitis and in 13 control
      subjects. We found increased mean levels of cICAM-1 both in serum (481
      micrograms.l-1) and in bronchial lavage (24 micrograms.l-1) in the COPD patients
      as compared to the controls (321 micrograms.l-1 in serum, 15 micrograms.l-1 in
      lavage). We also found higher mean levels of cE-selectin in serum from the COPD
      patients (86 micrograms.l-1) compared to controls (50 micrograms.l-1). The serum
      levels of cE-selectin correlated significantly with lung function measured as
      forced expiratory volume in one second (FEV1) in percentage of predicted.
      Patients with significant intrabronchial bacterial colonization had increased
      levels of serum cE-selectin. Our results indicate that cCAMs may reflect an
      upregulation of CAMs on endothelial and epithelial airway cells in COPD.

PMID- 7527790
TI  - Termination-altering amino acid substitutions in the beta' subunit of Escherichia
      coli RNA polymerase identify regions involved in RNA chain elongation.
AB  - To identify regions of the largest subunit of RNA polymerase that are potentially
      involved in transcript elongation and termination, we have characterized amino
      acid substitutions in the beta' subunit of Escherichia coli RNA polymerase that
      alter expression of reporter genes preceded by terminators in vivo. Termination
      altering substitutions occurred in discrete segments of beta', designated 2, 3a,
      3b, 4a, 4b, 4c, and 5, many of which are highly conserved in eukaryotic homologs
      of beta'. Region 2 substitutions (residues 311-386) are tightly clustered around
      a short sequence that is similar to a portion of the DNA-binding cleft in E. coli
      DNA polymerase I. Region 3b (residues 718-798) corresponds to the segment of the
      largest subunit of RNA polymerase II in which amanitin-resistance substitutions
      occur. Region 4a substitutions (residues 933-936) occur in a segment thought to
      contact the transcript 3' end. Region 5 substitutions (residues 1308-1356) are
      tightly clustered in conserved region H near the carboxyl terminus of beta'. A
      representative set of mutant RNA polymerases were purified and revealed
      unexpected variation in percent termination at six different rho-independent
      terminators. Based on the location and properties of these substitutions, we
      suggest a hypothesis for the relationship of subunits in the transcription
      complex.

PMID- 7527789
TI  - Regulation of pyrBI operon expression in Escherichia coli by UTP-sensitive
      reiterative RNA synthesis during transcriptional initiation.
AB  - Pyrimidine-mediated regulation of pyrBI operon expression in Escherichia coli K
      12 occurs through UTP-sensitive transcriptional attenuation and through a second
      mechanism that functions at the level of transcriptional initiation. In this
      study we demonstrate that this second control mechanism is based on UTP-sensitive
      reiterative RNA synthesis within a run of three T-A base pairs in the pyrBI
      initially transcribed region. Our results show that high UTP levels induce the
      synthesis in vitro of nascent transcripts with the sequence AAUUUUn (where n = 1
      to > 30), which are not extended downstream to include pyrBI sequences. Synthesis
      of these transcripts, which are initiated at the predominant in vivo
      transcriptional start site, inhibits the production of full-length pyrBI
      transcripts. A TTT to GTA mutation in the pyrBI initially transcribed region
      eliminates reiterative transcription and stimulates productive transcription in
      vitro. When introduced into the E. coli chromosome, this mutation causes a
      sevenfold increase in pyrBI expression in cells grown under conditions of
      pyrimidine excess and nearly abolishes pyrimidine-mediated regulation of pyrBI
      expression when coupled with a mutation that eliminates attenuation control.
      Additional experiments indicate that the context of the three T-A base pairs
      within the pyrBI initially transcribed region is important for reiterative
      transcription. A possible mechanism for reiterative transcription and the likely
      involvement of this process in the regulation of other genes are discussed.

PMID- 7527792
TI  - Thyrotropin-secreting adenoma in an adolescent girl without increased serum
      thyrotropin-alpha.
AB  - A 13-year-old girl with poor weight gain and pubertal delay was referred for
      hyperthyroidism. Slightly elevated levels of circulating thyroid hormones failed
      to suppress circulating thyrotropin (TSH) levels. Despite appropriate thyrotropin
      releasing hormone stimulation of TSH secretion, a thyrotropin-secreting pituitary
      adenoma was identified as the cause of inappropriate TSH secretion.

PMID- 7527791
TI  - [Nonsurgical treatment of unruptured ectopic pregnancy with methotrexate (MTX)
      (introductory remarks)].
AB  - Seven patients with an unruptured tubal pregnancy were treated with a single i.m.
      injection of methotrexate (1 mg per Kg) and monitored with beta hCG titer and
      ultrasound examination. Two of them required two doses for declining beta hCG
      titer. Among four infertile patients HSG done on two subsequently demonstrated
      tubal patency on the involved side in one patient.

PMID- 7527794
TI  - Hypertension increases insulin-like growth factor binding protein-4 mRNA levels
      in rat aorta.
AB  - Insulin-like growth factor-I (IGF-I) is an endocrine and autocrine/paracrine
      growth factor. Recently, we have demonstrated that interrenal aortic coarctation
      in the rat increases IGF-I mRNA levels in the thoracic aorta, consistent with a
      role for this mitogen in hypertensive vascular remodeling. The effects of IGF-I
      are modulated by several IGF binding proteins including IGFBP-3, the main
      circulating carrier of IGF-I, and IGFBP-4, the main IGF binding protein produced
      by vascular smooth muscle cells in vitro. To obtain insights into the regulation
      of IGF-I and more specifically to study potential changes in IGF binding proteins
      in high-renin hypertension, we studied male Sprague-Dawley rats that had
      undergone abdominal aortic coarctation. Compared with sham-operated rats, the
      study rats showed a rapid increase in IGFBP-4 mRNA levels in the hypertensive
      (thoracic) aorta, reaching a plateau at 3 days (2.5-fold increase) and persisting
      for at least 14 days. In striking contrast, IGFBP-4 mRNA decreased slightly in
      the normotensive (abdominal) aorta at 14 days. IGFBP-3 mRNA levels did not change
      in either vascular bed after coarctation. Study of hepatic tissue indicated that
      in coarcted rats IGFBP-4 and IGFBP-3 mRNA levels decreased transiently
      (approximately 50% at 7 days compared with sham). Circulating IGF-I in coarcted
      animals decreased slightly (P = .08), and Western ligand analysis indicated that
      circulating levels of IGF binding proteins were not altered.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7527793
TI  - Role of metabotropic glutamate receptors in ventrolateral medulla of hypertensive
      rats.
AB  - Evidence is accumulating for the role of metabotropic, as well as ionotropic,
      glutamate receptors in cardiovascular regulation. We sought to determine whether
      stimulation of metabotropic glutamate receptors in the rostral ventrolateral
      medulla would evoke enhanced cardiovascular responses in spontaneously
      hypertensive rats (SHR). Thus, we microinjected (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylic acid [(1S,3R)-ACPD], a selective agonist of metabotropic glutamate
      receptors, into the rostral ventrolateral medulla of urethane-anesthetized adult
      SHR and age-matched Wistar-Kyoto (WKY) rats. Microinjection of (1S,3R)-ACPD (1
      nmol/50 nL) produced increases in mean arterial pressure and splanchnic
      sympathetic nerve activity in SHR (+41 +/- 6 mm Hg and +34 +/- 4%, respectively)
      that were significantly greater than those observed in WKY rats (+18 +/- 3 mm Hg
      and +22 +/- 3%, P < .005 and P < .05, respectively). The pressor responses evoked
      by microinjection of L-glutamate (2 nmol), N-methyl-D-aspartate (20 pmol), or
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (5 pmol) were also
      significantly (P < .001) augmented in SHR (+55 +/- 3, +61 +/- 7, and +53 +/- 5 mm
      Hg, respectively, in SHR versus +31 +/- 1, +30 +/- 3, and +28 +/- 2 mm Hg in WKY
      rats). Results indicate that stimulation of metabotropic, as well as ionotropic,
      glutamate receptors in the rostral ventrolateral medulla evokes enhanced
      cardiovascular responses in SHR, which may contribute to hypertension in this
      model.

PMID- 7527795
TI  - Calcium current in smooth muscle cells from normotensive and genetically
      hypertensive rats.
AB  - Genetic hypertension results from numerous phenotypic expressions. We
      hypothesized that increased calcium current in vascular smooth muscle of
      genetically hypertensive animals is partly responsible for observed increases in
      agonist sensitivity, contractility, and calcium influx. Using adult,
      spontaneously hypertensive stroke-prone rats (SHRSP) and normotensive Wistar
      Kyoto (WKY) controls from an inbred colony, we characterized calcium current in
      smooth muscle cells isolated from cerebral arteries. Calcium current in WKY cells
      reached a maximum of -27.7 +/- 2.7 pA (n = 32) at +20 mV. Peak inward current at
      +20 mV in SHRSP cells had a mean amplitude of -44.4 +/- 3.0 pA (n = 72, P < .05).
      SHRSP cells exhibited a higher calcium current density. Maximal inward current
      normalized to cell capacitance yielded mean values of 2.07 +/- 0.11 pA/pF for WKY
      (n = 32) and 2.80 +/- 0.12 pA/pF (n = 79) for SHRSP (P < .05) cells. Transient
      type Ca2+ channel current had the same magnitude and current-voltage relation in
      both cell types, giving an L-type/T-type ratio of 3.85 for WKY and 6.25 for SHRSP
      cells. The voltage-dependent inactivation curve for SHRSP calcium current was
      shifted to the right only over the range of -50 to -30 mV, but the half-maximal
      inactivation voltages and Boltzmann coefficients were not significantly different
      between cell types. Increased calcium inward current in this model of genetic
      hypertension could account in part for altered calcium homeostasis and increased
      vascular reactivity, contributing to hypertension and vasospasm.

PMID- 7527797
TI  - Impact of radiation dose and tumor size on large cell lymphoma patients in
      complete response after integrated CHOP-Bleo-radiation treatment protocol.

PMID- 7527796
TI  - Influence of radiotherapy on node-positive prostate cancer treated with androgen
      ablation.
AB  - PURPOSE: Patients with node-positive prostate cancer that is regionally localized
      (T1-4, N1-3, M0) have a relatively poor prognosis when a single-treatment
      modality such as radical surgery, definitive radiotherapy, or androgen ablation
      is used. While promising results using radical surgery and androgen ablation have
      been reported, there are no data to support an analogous approach using local
      radiotherapy and androgen ablation. In this retrospective review, the outcome
      after local radiotherapy and early androgen ablation (XRT/HORM) was compared to
      early androgen ablation alone (HORM). METHODS AND MATERIALS: Between 1984 and
      1992 there were 181 patients treated with HORM and 27 patients treated with
      XRT/HORM at the University of Texas M. D. Anderson Cancer Center. The nodal
      status of all patients was established pathologically by lymph node dissection,
      which was terminated after frozen section confirmation of involvement. In the
      majority of cases androgen ablation was by orchiectomy. The median dose to the
      prostate in XRT/HORM group was 66 Gy. The median follow-up was 45 months; 49
      months for the HORM group and 25 months for the XRT/HORM group. RESULTS: The
      distribution of prognostic factors between the HORM and XRT/HORM groups was
      similar, with the exception of tumor grade. There was a significantly larger
      proportion of high grade tumors in the HORM group. In terms of actuarial disease
      outcome, at 4 years the results of patients in the HORM group were significantly
      worse, including a rising prostate specific antigen (PSA) of 53%, any disease
      progression of 32%, a rising PSA or disease progression of 55%, and local
      progression of 22%. None of the patients in the XRT/HORM group failed
      biochemically or clinically. To determine the impact of grade on these findings,
      the analyses were repeated, using only those with grade 2 tumors. A similar
      pattern was evidenced with significantly worse actuarial outcome at 4 years for
      the HORM group using the endpoints of a rising PSA (46%), any disease progression
      (24%), and a rising PSA or disease progression (47%). CONCLUSION: Node-positive
      prostate cancer patients with regionally localized disease fared significantly
      better when combined local radiotherapy and early androgen ablation were used, as
      compared to early androgen ablation alone. Although the number of patients in the
      XRT/HORM group was small and follow-up was short, the combined treatment had a
      dramatic effect on disease outcome and, therefore, a larger prospective
      randomized trial is warranted.

PMID- 7527799
TI  - Significance of tumor size and radiation dose to local control in stage I-III
      diffuse large cell lymphoma treated with CHOP-Bleo and radiation.
AB  - PURPOSE: The purpose of this study was to evaluate the possible effect of
      adjunctive involved field (IF) radiotherapy on long-term local control for
      patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who
      achieved a complete remission on a combined modality program which included
      cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP
      Bleo). METHODS AND MATERIALS: One hundred and ninety patients with Ann Arbor
      Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were
      undertaken to determine (a) response to treatment according to stage, extent of
      maximum local disease, and irradiation dose either < 40 Gy or > or = 40 Gy and
      (b) relapse patterns. RESULTS: A complete remission (CR) was achieved in 162
      patients. Among patients who achieved a CR, local control was better for those
      who received tumor doses of > or = 40 Gy (97%) than for those who received < 40
      Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding
      control rates were 88% and 71%, respectively. A study of distant relapse patterns
      following a CR showed that the first relapse usually involved an extranodal site.
      CONCLUSION: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for
      patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested
      that total nodal irradiation (TNI) possibly could have benefited a small subset
      of patients.

PMID- 7527800
TI  - Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin
      synthesis, and vascular permeability.
AB  - PURPOSE: To investigate the profile of biochemical and physiological changes
      induced in the rat spinal cord by radiation, over a period of 8 months. METHODS
      AND MATERIALS: The thoraco-lumbar spinal cords of Fisher rats were irradiated to
      a dose of 15 Gy. The rats were then followed and killed at various times
      afterward. Serotonin (5-HT) and its major metabolite 5-hydroxyindole-3-acetic
      acid (5-HIAA) were assayed as well as prostaglandin synthesis. Microvessel
      permeability was assessed by quantitative evaluation of Evans blue dye
      extravasation. RESULTS: None of the rats developed neurologic dysfunction, and
      histologic examination revealed only occasional gliosis in the ventral white
      matter at 240 days after irradiation. Serotonin levels were unchanged at 2, 14,
      and 56 days after radiation but increased at 120 and 240 days in the irradiated
      cord segments when compared to both the nonirradiated thoracic and cervical
      segments (p < 0.01) and age-matched controls (p < 0.03). The calculated
      utilization ratio of serotonin (5-HIAA/5-HT) remained unchanged. Immediately
      after radiation (at 3 and 24 h) an abrupt but brief increase in the synthesis of
      prostaglandin-E2 (PGE2), thromboxane (TXB2), and prostacyclin [6 keto-PGF1 alpha
      (6KPGF)] was noted, which returned to normal at 3 days. This was followed after 7
      and 14 days by a significant fall off in synthesis of all three prostaglandins.
      Thereafter, at 28, 56, 120, and 240 days, escalated production of thromboxane
      followed, while prostacyclin synthesis remained markedly reduced (-88% of control
      level at 240 days). Up to 7 days after radiation the calculated TXB2/6KPGF ratio
      remained balanced, regardless of the observed abrupt early fluctuations in their
      rate of synthesis. Later, between 7 and 240 days after radiation, a significant
      imbalance was present which became more pronounced over time. In the first 24 h
      after radiation, a 104% increase in microvessel permeability was observed which
      returned to normal by 3 days. Normal permeability was maintained at 14 and 28
      days, but at 120 and 240 days a persistent and significant increase of 98% and
      73% respectively above control level was noted. CONCLUSIONS: Radiation induces
      severe impairment in microvessel function even in the histologically unaffected
      spinal cord, and alters the secretory phenotype of various cell systems in the
      central nervous system.

PMID- 7527802
TI  - Poster production by color laser imager.
AB  - The scientific poster is an important educational tool at most radiology
      meetings. The visual impact of the exhibit is important in attracting attention
      and conveying content to the reader. A new method of designing and producing full
      color transilluminated posters in the radiology department using a personal
      computer and color laser imager is described. The advantages of this approach are
      author control over the production process and production of a visually
      interesting exhibit.

PMID- 7527801
TI  - Assessment and psychotherapeutic intervention for an HIV-infected preschool
      child.
AB  - Pediatric acquired immunodeficiency syndrome (AIDS) is becoming more common.
      Moreover, human immunodeficiency virus (HIV) positive status in multiple family
      members is common and complicates disease management. Practitioners treating
      these children are often unaware of the effect of the virus on the child's
      psychological, cognitive, and emotional functioning. In addition, children with
      AIDS frequently come from families facing pressing social problems, including
      homelessness, poverty, and drug addiction. HIV-positive children thus confront
      such diverse issues as the deterioration of developmental skills, social
      ostracism, and the possibility of imminent death, placing them in a
      socioemotional crisis. This paper presents a comprehensive psychotherapeutic
      intervention for such children.

PMID- 7527798
TI  - Observations of pretreatment prostate-specific antigen doubling time in 107
      patients referred for definitive radiotherapy.
AB  - PURPOSE: To determine pretreatment prostate-specific antigen doubling times
      (PSADT) in patients referred for definitive radiotherapy. METHODS AND MATERIALS:
      One hundred and seven patients with histologically proven nonmetastatic prostate
      cancer and an elevated prostate-specific antigen (PSA) who were referred for
      radiation therapy had three serum PSA values obtained prior to the start of
      definitive therapy. Prostate-specific antigen doubling times were calculated by
      linear regression. RESULTS: Prostate-specific antigen values increased during the
      period of observation in 78 patients (73%). Forty-three patients (40%) had
      calculated PSADT of less than 2 years and of those patients with pretreatment
      serum PSA values of greater than 10 ng/mL more than 50% has calculated PSADT of
      less than 2 years. CONCLUSIONS: A significant minority of patients referred for
      radiotherapy have calculated PSADT of less than 2 years. The significance of this
      relatively fast growth rate is as yet undetermined, but suggests that patients
      referred for radiotherapy may have aggressive disease prior to treatment.

PMID- 7527803
TI  - Prematurity, posture and the development of looking behaviour during early
      communication.
AB  - This study concerns the developing relationship between motor control and looking
      behaviour in full term (N = 15) and pre-term (N = 29) infants during face-to-face
      interaction with the mother at 6, 12 and 18 weeks of corrected age. Infants with
      inborn errors or major medical complications were excluded. In the pre-term
      infants the development of head and arm postures during interaction differed from
      the full term pattern, especially in infants born before 32 weeks and/or small
      for-gestational age. The full term infants were more advanced than other infants
      in the ability to grasp an object. These findings were related to group
      differences in looking behaviour, suggesting that differences in the development
      of looking behaviour may be (partly) accounted for by differences in the
      development of motor control.

PMID- 7527804
TI  - Descending propriospinal axons in the hindlimb enlargement of the red-eared
      turtle: cells of origin and funicular courses.
AB  - Spinal neurons with descending axons are important components of spinal
      sensorimotor networks. We used an anatomical tracing technique to study the
      distribution of descending propriospinal axons and cell bodies in red-eared
      turtles. We injected horseradish peroxidase into a portion of one funiculus in
      the middle of the hindlimb enlargement and examined six spinal segments rostral
      to the injection site (dorsal 3 through dorsal 8) for labeled neuronal cell
      bodies. Injections into each region of the white matter labeled substantial
      numbers of descending propriospinal neurons. Each injection labeled cell bodies
      over most of the six spinal segments examined. Each injection also labeled cell
      bodies in the ipsilateral dorsal horn, intermediate zone, and ventral horn as
      well as the contralateral intermediate zone and ventral horn. Injections into
      each of four regions of the white matter, the dorsal funiculus, the medial part
      of the lateral funiculus, the lateral part of the lateral funiculus, and the
      ventral funiculus reliably gave rise to a distinct distribution of labeled cell
      bodies. These experiments establish that descending propriospinal axons in red
      eared turtles are found in all regions of the spinal white matter. This finding
      contrasts with a popular contemporary view of the organization of descending
      propriospinal axons in mammals. These experiments also demonstrate that neurons
      in each region of the gray matter give rise to a different distribution of
      descending, funicular axons, although these distributions are widely overlapping.
      Different funicular axon distributions could be associated with different sets of
      synaptic contacts with the white-matter dendrites of spinal neurons.

PMID- 7527808
TI  - Distribution of nitric oxide synthase-immunoreactive interneurons in the spinal
      trigeminal nucleus.
AB  - The spinal trigeminal nucleus is involved in the transmission of orofacial
      sensory information. Neither the distribution of the neuromessenger, nitric
      oxide, within the trigeminal system nor the possible relationship of this simple
      gas with trigeminothalamic neurons has been carefully studied. Using
      immunocytochemical (against nitric oxide synthase) and histochemical (NADPH
      diaphorase staining) techniques, we have found that nitric oxide neurons and
      processes are more prominent in the nucleus caudalis and the dorsomedial aspect
      of the nucleus oralis than in other spinal trigeminal regions. To study the
      relationship of nitric oxide to trigeminothalamic neurons and intertrigeminal
      interneurons of the spinal trigeminal nucleus, spinal trigeminal neurons were
      retrogradely labeled with fluorogold by thalamic injections or by injections into
      the junction of the nucleus interpolaris and nucleus caudalis. Medullary sections
      were subsequently processed with NADPH-diaphorase histochemistry. None of the
      diaphorase-stained neurons in the spinal trigeminal nucleus was found to contain
      fluorogold; however, some diaphorase-stained processes were found in close
      proximity to trigeminothalamic neurons. Following spinal trigeminal nucleus
      injections, many diaphorase-stained neurons were found to contain fluorogold,
      especially in the nucleus caudalis, suggesting that nitric oxide-containing
      neurons in the spinal trigeminal nucleus are intertrigeminal interneurons.
      Collectively, these data indicate that nitric oxide is most prominent in
      interneurons located in nucleus caudalis and that these interneurons give rise to
      processes that appose trigeminothalamic neurons, raising the possibility that
      they may indirectly influence orofacial nociceptive processing at the level of
      the spinal trigeminal nucleus via nitric oxide production.

PMID- 7527807
TI  - Growth cones of regenerating retinal axons contact a variety of cellular profiles
      in the transected goldfish optic nerve.
AB  - Following optic nerve transection in goldfish, retinal axons regenerate. To
      determine what the growth cones use as a substrate for their growth, regenerating
      growth cones were labeled by horseradish peroxidase (HRP) application to the
      retina 5-6 days after intraorbital optic nerve section (ONS) and identified at 10
      11 days after ONS in the brain sided (distal) portion of the optic nerve in thick
      and serial ultrathin sections. Leading growth cones (n = 5) were found in
      intimate contact with a variety of elements: with myelin fragments alone, with
      myelin fragments and glial cells, and with the basal lamina of the glia limitans
      and the surface of a fibroblast outside the boundary of previous fascicles. In
      ultrathin sections of conventionally treated regenerating optic nerves,
      (unlabeled) axon profiles--in addition to myelin fragments--were seen to be in
      contact with an astrocyte and an oligodendrocyte, suggesting that the growth
      cones of these axons may have been associated with those cells. The data suggest
      that leading growth cones of regenerating axons may be capable of growing along
      myelin fragments and on a wide variety of cellular surfaces in the goldfish optic
      nerve.

PMID- 7527805
TI  - Architectonic subdivision of the orbital and medial prefrontal cortex in the
      macaque monkey.
AB  - The orbital and medial prefrontal cortex (OMPFC) of macaque monkeys is a large
      but little understood region of the cerebral cortex. In this study the
      architectonic structure of the OMPFC was analyzed with nine histochemical and
      immunohistochemical stains in 32 individuals of three macaque species. The stains
      included Nissl, myelin, acetylcholinesterase, Timm, and selenide stains and
      immunohistochemical stains for parvalbumin, calbindin, a nonphosphorylated
      neurofilament epitope (with the SMI-32 antibody), and a membrane-bound
      glycoprotein (with the 8b3 antibody). In addition to patterns of cell bodies and
      myelinated fibers, these techniques allow the visualization of markers related to
      metabolism, synapses, and neurotransmitters. A cortical area was defined as
      distinct if it was differentiated in at least three different stains and, as
      described in later papers, possessed a distinct set of connections. Twenty-two
      areas were recognized in the OMPFC. Walker's areas 10, 11, 12, 13, and 14 [J.
      Comp. Neurol. (1940) 73:59-86] have been subdivided into areas 10m, 10o, 11m,
      11l, 12r, 12l, 12m, 12o, 13m, 13l, 13a, 13b, 14r, and 14c. On the medial wall,
      areas 32, 25, and 24a,b,c have been delineated, in addition to area 10m. The
      agranular insula also has been recognized to extend onto the posterior orbital
      surface and has been subdivided into medial, intermediate, lateral,
      posteromedial, and posterolateral agranular insula areas. The OMPFC, therefore,
      resembles other areas of primate cortex, such as the posterior parietal and
      temporal cortices, where a large number of relatively small, structurally and
      connectionally distinct areas have been recognized. Just as the area-specific
      neurophysiological properties of these parietotemporal areas underlie broader
      regional functions such as visuospatial analysis, it is likely that the many
      small areas of the OMPFC also make differential contributions to the general
      mnemonic, sensory, and affective functions of this region.

PMID- 7527806
TI  - Central olfactory connections in the macaque monkey.
AB  - The connections between the olfactory bulb, primary olfactory cortex, and
      olfactory related areas of the orbital cortex were defined in macaque monkeys
      with a combination of anterograde and retrograde axonal tracers and
      electrophysiological recording. Anterograde tracers placed into the olfactory
      bulb labeled axons in eight primary olfactory cortical areas: the anterior
      olfactory nucleus, piriform cortex, ventral tenia tecta, olfactory tubercle,
      anterior cortical nucleus of the amygdala, periamygdaloid cortex, and olfactory
      division of the entorhinal cortex. The bulbar axons terminate in the outer part
      of layer I throughout these areas and are most dense in areas that are close to
      the lateral olfactory tract. Labeled axons also were found in the superficial
      part of nucleus of the horizontal diagonal band. Retrograde tracers injected into
      the olfactory bulb labeled cells in the nucleus of the diagonal band and in all
      of the primary olfactory cortical areas except the olfactory tubercle. Electrical
      stimulation of the olfactory bulb evoked short-latency unit responses and a
      characteristic field wave in the primary olfactory cortex. Multiunit activity in
      layer II tended to be of shorter latency than that in layer III and the
      endopiriform nucleus. Associational connections within the primary olfactory
      cortex were demonstrated with anterograde tracer injections into the piriform
      cortex and the entorhinal cortex. Injections into the piriform cortex near the
      lateral olfactory tract labeled axons in the deep part of layer I of many primary
      olfactory areas, but especially in areas near the tract. An injection into the
      rostral entorhinal cortex, distant to the lateral olfactory tract, labeled a
      complementary distribution of axons in deep layer I of olfactory areas medial and
      caudoventral to the tract. This organization resembles that reported in the
      primary olfactory cortex of the rat [Luskin and Price (1983) J. Comp. Neurol.
      216:264-291]. The anterograde tracer injections into the piriform cortex and
      retrograde tracer injections into the orbital and medial prefrontal cortex and
      rostral insula label connections from the primary olfactory cortex to nine areas
      in the caudal orbital cortex, including the agranular insula areas Iam, Iai, Ial,
      Iapm, and Iapl and areas 14c, 25, 13a, and 13m. The piriform cortex projects most
      heavily to layer I of these areas. Only Iam, Iapm, and 13a receive a substantial
      projection to the deeper layers. Areas Iam, Iapm, and 13a were also the only
      areas that responded with multiunit action potentials to olfactory bulb
      stimulation in anesthetized animals.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7527809
TI  - Mapping the bovine homolog of the human cystic fibrosis gene.
AB  - Human cDNA probe H1.6 (clone 10-1) encoding cystic fibrosis transmembrane
      conductance regulator (CFTR) was used to map the bovine homolog of CFTR. Using a
      panel of bovine x rodent hybrid somatic cells, the homolog was mapped to bovine
      syntenic group U13 which corresponds to chromosome 4. CFTR is 97.7% concordant
      with syntenic markers T-cell receptor beta (TCRB) and P-glycoprotein 3 (PGY3).
      The comparative gene maps of CFTR, TCRB, and PGY3 on human chromosome 7, bovine
      chromosome 4, and mouse chromosome 5 and 6 indicate conservation of synteny,
      although internal rearrangements relative to HSA 7 are present in both cattle and
      mice.

PMID- 7527810
TI  - Modulation of immunogenicity and antigenicity of proteins by maleylation to
      target scavenger receptors on macrophages.
AB  - We have maleylated proteins to target macrophage-specific scavenger receptors and
      have used this system to study changes in the epitopes and immunogenicity of such
      proteins. We show that maleylation of diphtheria toxoid (DT) induces targeting to
      macrophage scavenger receptors and enhances its immunogenicity. DT does not evoke
      detectable serum Ab responses upon injection as soluble protein. However,
      maleylated DT (mDT) does generate a significant Ab response. Furthermore,
      immunization with soluble mDT leads to a better T cell proliferative response in
      vitro than immunization with DT can generate, thereby demonstrating that
      maleylation leads to enhanced T cell immunogenicity in vivo. We also find that
      maleylation disrupts the native B cell epitopes of DT and creates new epitopes,
      because antisera to DT and mDT do not cross-react. At least some of the new
      epitopes generated are maleylation specific, because antisera against various
      maleylated proteins do cross-react. In contrast, maleylation does not
      significantly modify the repertoire of T cell epitopes generated from DT, because
      T cells generated by either DT or mDT immunization are cross-reactive, and both
      DT and mDT can stimulate T cells that are specific for single synthetic DT
      peptide. Maleylated proteins are better presented in vitro than are their native
      counterparts, and this enhancement of presentation is blocked by unrelated
      maleylated proteins. These results suggest that Ags targeted to scavenger
      receptors on macrophages by maleylation are better presented to T cells and are
      immunogenic in vivo without adjuvant.

PMID- 7527811
TI  - Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate
      biologic activity.
AB  - IL-12, a heterodimeric cytokine, consists of two disulfide-linked subunits, p40
      and p35. We investigated the role of p40 in ligand binding and signal
      transduction by expressing this subunit alone in COS cells. Culture media of the
      transfected COS cells exhibited specific dose-dependent binding to KIT225/K6
      cells, a human T cell line that expresses IL-12R. Analysis of the culture media
      by SDS-PAGE and Western blotting demonstrated the presence of 40-kDa monomers and
      80-kDa disulfide-linked homodimers. The two p40 species were purified and
      identified by N-terminal sequencing and proteolytic peptide mapping.
      Characterization of the p40 proteins for binding and bioactivity showed that both
      the p40 monomer and dimer inhibited 125I-labeled IL-12 binding to IL-12R, but the
      80-kDa species, having a 50% inhibitory concentration (IC50) of 20 to 70 ng/ml,
      was at least 20-fold more effective than the monomer. Although neither the
      monomer nor the dimer stimulated human PHA-blast proliferation, the 80-kDa dimer
      inhibited IL-12-induced proliferation in a dose-dependent manner with an IC50 of
      65 ng/ml. The results suggest that the IL-12 p40 subunit contains the essential
      epitopes for receptor binding. However, a proper conformation required for high
      affinity binding is achieved only when p40 is associated with a p35 subunit or
      another p40 subunit. When p40 is associated with a p35 subunit, the heterodimer
      acts as an agonist mediating biologic activity. However, when p40 associates with
      another p40, the homodimer behaves as an antagonist in vitro.

PMID- 7527812
TI  - Several HLA alleles share overlapping peptide specificities.
AB  - Herein we describe the establishment of assays to measure peptide binding to
      purified HLA-B*0701, -B*0801, -B*2705, -B*3501-03, -B*5401, -Cw*0401, -Cw*0602,
      and -Cw*0702 molecules. The binding of known peptide epitopes or naturally
      processed peptides correlates well with HLA restriction or origin, underscoring
      the immunologic relevance of these assays. Analysis of the sequences of various
      HLA class I alleles suggested that alleles with peptide motifs characterized by
      proline in position 2 and aromatic or hydrophobic residues at their C-terminus
      shared key consensus residues at positions 9, 63, 66, 67, and 70 (B pocket) and
      residue 116 (F pocket). Prediction of the peptide-binding specificity of HLA
      B*5401, on the basis of this consensus B and F pocket structure, verified this
      hypothesis and suggested that a relatively large family of HLA-B alleles (which
      we have defined as the HLA-B7-like supertype) may significantly overlap in
      peptide binding specificity. Availability of quantitative binding assays allowed
      verification that, indeed, many (25%) of the peptide ligands carrying proline in
      position 2 and hydrophobic/aromatic residues at the C-terminus (the B7-like
      supermotif) were capable of binding at least three of five HLA-B7-like supertype
      alleles. Identification of epitopes carrying the B7-like supermotif and binding
      to a family of alleles represented in over 40% of individuals from all major
      ethnic groups may be of considerable use in the design of peptide vaccines.

PMID- 7527814
TI  - Inhibition of neutrophil adhesion by adenosine and an adenosine kinase inhibitor.
      The role of selectins.
AB  - Adenosine and adenosine analogues exhibit anti-inflammatory effects in vitro and
      in vivo, but their usefulness is limited by profound cardiovascular side effects.
      Therefore, we synthesized inhibitors of an enzyme involved in adenosine
      metabolism, adenosine kinase (AK) (EC 2.7.1.20), to enhance endogenous adenosine
      concentrations at sites of inflammation. GP-1-515 (4-amino-1-(5-amino-5-deoxy-1
      beta-D- ribofuranosyl)-3-bromo-pyrazolo[3,4-d]pyrimidine), a novel AK inhibitor,
      decreased adhesion of activated human neutrophils to cultured endothelial cell
      monolayers by increasing local adenosine levels. The mechanism of inhibition in
      this assay seemed to involve selectin blockade and was independent of the beta 2
      integrins. GP-1-515 and 2-chloroadenosine (a nonmetabolizable adenosine analogue)
      had no effect on the surface expression or shedding of adhesion molecules. An
      agent that disrupts the cytoskeleton, cytochalasin B, mimicked the effect of
      adenosine on cell adhesion. Interactions between L-selectin and the neutrophil
      cytoskeleton might be altered by adenosine and could contribute to adenosine
      mediated adhesion inhibition.

PMID- 7527813
TI  - The E2 molecule (CD99) specifically triggers homotypic aggregation of CD4+ CD8+
      thymocytes.
AB  - We have previously described E2 as a 32-kDa transmembrane glycoprotein displaying
      an isomorphism, as two epitopes (defined by mAbs O662 and L129) are widely
      distributed on T cells whereas two epitopes are restricted to T cell subsets
      (defined by mAbs D44 and 12E7). E2, the MIC-2 gene product, is involved in T cell
      adhesion because anti-E2 mAbs against pan T epitopes block spontaneous T cell
      rosettes. Pan T E2 mAbs are also able to induce exposure of the
      phosphatidylserine at the thymocyte surface but not at the surface of mature T
      lymphocytes, an event most likely linked to adhesion phenomena. We now show here
      that the anti-E2 mAbs (0662 and L129) that block rosettes and induce
      phosphatidylserine exposure at the thymocyte surface, and not those reacting with
      epitopes not involved in adhesion, also trigger aggregation of certain immature T
      cell lines and no other cell lines tested. Among the normal cells tested, anti-E2
      mAbs exclusively induce homotypic aggregation of CD4+ CD8+ human thymocytes. This
      phenomenon is temperature, energy, and Mg++ dependent, and requires an intact
      cytoskeleton. These adhesion properties are rather characteristic of integrins.
      Nevertheless, mAb against beta 1, beta 2, and beta 3 integrin chains, as well as
      those against alpha-chains known to be present on thymocytes, are unable to block
      corticothymocyte aggregation. We conclude that E2 triggers on corticothymocytes
      and no other T cells a homotypic adhesion pathway most likely mediated by an
      uncharacterized integrin.

PMID- 7527816
TI  - Experimental autoimmune encephalomyelitis-resistant mice have highly
      encephalitogenic myelin basic protein (MBP)-specific T cell clones that recognize
      a MBP peptide with high affinity for MHC class II.
AB  - BALB/c mice are resistant to disease induction when experimental protocols that
      induce experimental autoimmune encephalomyelitis (EAE) in susceptible strains of
      animals are used. We have previously described a panel of myelin basic protein
      (MBP)-specific CD4+ T cell clones from BALB/c mice, two of which induce moderate
      EAE when transferred to syngeneic recipients. These clones are I-E(d) restricted
      and recognize residues 151-160 of mouse MBP. Here, we describe a series of 17 MBP
      reactive T cell clones, which were derived from two BALB/c mice. All are I-A(d)
      restricted and recognize nested epitopes in peptide 59-76 of mouse MBP. Four
      different TCR V beta chains are used by this panel of clones; these include V
      beta 8.2 (10/17), V beta 8.1 (2/17), V beta 7 (3/17), and V beta 14 (2/17).
      Twelve of fourteen clones tested adoptively transferred severe demyelinating EAE
      to syngeneic recipients. Studies of relative binding affinities of MBP peptides
      to class II molecules I-A(d) and I-E(d) show that peptide 59-76 binds with
      extremely high affinity to I-A(d), whereas three peptides that contains residues
      151-160 bind poorly to I-E(d). These results are consistent with a growing number
      of reports that show that high affinity binding to class II is required for
      autoantigenic stimulation. Despite encephalitogenicity of 59-76-reactive T cells,
      active immunization of BALB/c mice with peptide 59-76 in adjuvant failed to
      induce either clinical or histologic signs of EAE. The implications of these
      findings for mechanisms of genetically determined EAE resistance are discussed.

PMID- 7527815
TI  - Murine KIT+ lineage- bone marrow progenitors express Fc gamma-RII but do not
      express Fc epsilon-RI until mast cell granule formation.
AB  - We examined the expression of Fc epsilon-RI and Fc gamma-RII/III on mouse bone
      marrow cells enriched for hematopoietic progenitors including mast cell
      progenitors. Bone marrow cells were depleted of mature hematopoietic lineages and
      a primitive population of cells that express the proto-oncogene c-kit (KIT+
      lineage- cells) was isolated. KIT+ lineage- cells stain positively using the Ab
      2.4G2, indicating surface expression of Fc gamma-RII and/or Fc gamma-RIII.
      Fluorescent staining of intracytoplasmic domains of Fc gamma-RII and Fc gamma
      RIII revealed that these cells express primarily Fc gamma-RII on their surface.
      KIT+ lineage- cells did express Fc gamma RIII alpha-chain protein, but
      predominately in the nuclear/perinuclear area. We could not detect surface
      expression of Fc epsilon-RI by KIT+ lineage- cells, although a heterogeneous
      population of KIT- cells does bind IgE with high affinity and may reflect cells
      of the basophilic lineage. KIT+ lineage- cells cultured with SCF and IL-3
      generate numerous mast cells, whereas equivalent numbers of KIT- cells or naive
      bone marrow cells do not. In these cultures, surface expression of Fc epsilon-RI
      is detected on a small number of cells by day 3 of culture with increased surface
      expression levels correlating roughly with metachromatic granule formation. The
      fact that Fc gamma-RIII and Fc epsilon-RI are not expressed on the cell surface
      of KIT+ lineage- cells but appear later in hematopoietic development makes it
      unlikely that these receptors influence early hematopoietic differentiation. The
      role that might justify such a complete surface expression of Fc gamma-RII by
      bone marrow progenitors remains to be identified.

PMID- 7527817
TI  - A peptide-based human T cell leukemia virus type I vaccine containing T and B
      cell epitopes that induces high titers of neutralizing antibodies.
AB  - We have recently identified the principal linear neutralizing B cell epitopes of
      human T cell leukemia virus type I (HTLV-I) on the envelope protein gp46, amino
      acids (aa) 187-199, by using a number of human mAbs. We therefore propose that
      this region would be a good candidate for a peptide-based HTLV-I vaccine. To
      develop a peptide-based vaccine that can induce a high titer of neutralizing Abs
      against HTLV-I, we first synthesized peptides of various lengths containing aa187
      199. Because the addition of gp46 aa181-186 or aa200-210 to either the N-terminus
      or C-terminus of SP187-199 did not alter the antigenicity of the principal
      neutralizing determinant, we prepared two peptide-based vaccines, MAP181-203 and
      MAP181-210, by conjugating SP181-203 and SP181-210 with a branched polylysine
      oligomer. In rabbits, X4 to X8 and X8 to X64 titers of the neutralizing Abs were
      induced by immunization with MAP181-203 and MAP181-210, respectively.
      Furthermore, high titers of neutralizing Abs (X40 to X320) were elicited in five
      different strains of rats by immunization with MAP181-210. We also identified the
      major T cell epitope on gp46 aa194-210 in various strains of rats immunized with
      MAP181-210. Furthermore, the peripheral T lymphocytes obtained from the majority
      of HTLV-I-infected patients including HTLV-I-associated myelopathy/tropical
      spastic paraparesis, adult T cell leukemia/lymphoma, and healthy carriers,
      proliferated in response to the peptides containing aa194-210. These results
      indicated that MAP181-210 contains a T cell helper epitope on aa194-210 not only
      in rats and rabbits, but also in humans with various HLA haplotypes. It is
      therefore possible that MAP181-210 could become one of the candidates for a
      peptide-based HTLV-I vaccine for human use.

PMID- 7527818
TI  - Monoclonal IgM rheumatoid factor secreted by CD5-negative B cells during mixed
      cryoglobulinemia. Evidence for somatic mutations and intraclonal diversity of the
      expressed VH region gene.
AB  - Mixed cryoglobulinemia is usually considered to be a nonmalignant human B cell
      proliferation that produces a monoclonal IgM rheumatoid factor (RF). Important
      immunologic similarities and differences were described between the monoclonal B
      cells during mixed cryoglobulinemia and during malignant chronic lymphocytic
      leukemia (CLL):high frequency of the same VH and V kappa gene usage by both types
      of monoclonal B cells producing IgM with RF activity, apparent intraclonal
      homogeneity, but different expression of the pan T cell CD5 Ag. The description
      of an unusual CD5-negative B cell CLL case secreting a mutated IgM RF led the
      authors to suggest that the usage of non-mutated germline Ig genes is a property
      of cells derived from the CD5 lineage or stage of differentiation, rather than an
      intrinsic property of CLL or of IgM RF-producing cells in general. Because mixed
      cryoglobulinemia cells are usually CD5-negative, it was of interest to test for
      the existence of mutations in the VH and V kappa regions, as well as for the
      intraclonal homogeneity of the expressed Ig genes. In this study, we used the PCR
      technique to analyze the monoclonal rheumatoid factor (mRF) V genes from a
      patient with mixed cryoglobulinemia. We show that the CD5-negative monoclonal B
      cells express a slightly mutated V kappa 3 gene, but a more mutated VH1 gene
      whose genomic counterpart was shown to be the 51p1 germline gene. The sequence
      analysis of several independent clones shows some degree of intraclonal
      diversity, suggesting the existence of a clonal filiation. These results are
      discussed in terms of the origin of the monoclonal B cell during mixed
      cryoglobulinemia and CLL.

PMID- 7527819
TI  - HIV-1 infection alters monocyte interactions with human microvascular endothelial
      cells.
AB  - HIV infection of monocytes resulted in twofold elevation of adhesion molecule LFA
      1 (both alpha L/CD11a and beta 2/CD18 subunits) and LFA-3 (CD58), with no
      apparent increase in LFA-2 (CD2) or various beta 1-integrins. Homotypic
      aggregation of monocytes was evident 2 h after exposure to virus and was
      inhibited by mAbs to both the alpha L- and beta 2-subunits of LFA-1. HIV-infected
      monocytes also showed a marked increase in adherence to human capillary
      endothelial cell monolayers derived from brain, lung, and skin. This adherence
      was inhibited by mAb to either LFA-1 subunit and by mAb to the counter-receptor
      intercellular adhesion molecule-1. Cocultivation of HIV-infected monocytes with
      endothelial cells increased permeability of endothelial cell monolayers to 125I
      albumin in transwell assay systems. The increased endothelial permeability
      induced by HIV-infected monocytes was associated with a substantial disruption of
      the endothelial cell monolayer. Morphologic disruption was not a direct toxic
      effect on endothelial cells, but appeared to be secondary to changes in
      endothelial cell-cell or cell-matrix interactions. Northern blot analysis showed
      increased expression of gelatinase B (92-kDa gelatinase), tissue inhibitor of
      metalloproteinase TIMP-1, and TIMP-2 in the HIV-infected monocytes. Consistent
      with these Northern analyses, secretion of gelatinase activity in culture fluids
      of HIV-infected monocytes was also increased and was dependent on the stage of
      virus replication. Incubation of HIV-infected monocytes with the proteinase
      inhibitors TIMP-1 and TIMP-2 inhibited the increased permeability of endothelial
      cell monolayers to 125I albumin. These results suggest possible mechanisms for
      extravasation of HIV-infected monocytes through vascular endothelium into tissue
      in early stages of HIV disease.

PMID- 7527820
TI  - In vivo depletion of Thy-1-positive cells originating from normal bone marrow
      abrogates the suppression of gld disease in normal-gld mixed bone marrow
      chimeras.
AB  - Mice homozygous for gld develop an autoimmune syndrome characterized by
      hypergammaglobulinemia, massive accumulation of abnormal T cells and the
      production of autoantibodies. Previous studies in our laboratory have shown that
      reconstitution of lethally irradiated B6/gld recipients with a mixture of normal
      and gld bone marrow (BM) suppresses the gld-induced syndrome. In this report we
      extend this observation by demonstrating that the depletion of normal Thy-1+
      cells, but not normal B cells, restores gld disease in mixed BM chimeras congenic
      for Thy-1 and IgH alleles. These results strongly suggest that normal T cells
      suppress the development of gld-related abnormalities. It is probable that the
      mechanism by which normal Thy-1+ cells mediate the suppression is Fas ligand
      dependent.

PMID- 7527821
TI  - Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production
      correlates with improved disease course.
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease
      characterized by central nervous system inflammation and demyelination. Retinoids
      regulate cell differentiation and growth by binding to and activating retinoic
      acid receptors, which seem to be nuclear transcription factors. The effect of
      retinoids on chronic relapsing EAE produced by the transfer of myelin basic
      protein (MBP)-specific lymph node cells (LNC) was studied. All-trans-retinoic
      acid (tRA) inhibited the proliferation of MBP-specific LNC in vitro. However, the
      capacity of these cells to transfer EAE was markedly reduced by concentrations of
      tRA that only mildly inhibited T cell proliferation. The presence of tRA during
      in vitro MBP-specific LNC activation resulted in a considerable increase in IL-4
      mRNA, whereas mRNA for IL-2, TNF-alpha, and IFN-gamma was decreased. Increased IL
      4 also was detected in culture supernatants. However, the presence of a
      neutralizing Ab to IL-4 (11B11) during MBP-specific LNC activation in vitro did
      not reverse the inhibition of encephalitogenicity caused by tRA. The
      administration of retinoids in vivo resulted in an improved clinical course, even
      when given after disease onset. These findings suggest that T cell activation in
      the presence of tRA results in the development of T cells of the Th2 phenotype,
      which, in turn, might be responsible for the decrease in the encephalitogenicity
      of MBP-specific T cells. The modulation by retinoids of an immune response
      dominated by Th1-like T cells to one in which the protective cytokines of Th2
      like cells predominate may have potential relevance for human demyelinating
      diseases such as multiple sclerosis.

PMID- 7527822
TI  - Co-infusion of normal bone marrow partially corrects the gld T-cell defect.
      Evidence for an intrinsic and extrinsic role for Fas ligand.
AB  - Ipr and gld mice develop systemic autoimmune diseases with nearly
      indistinguishable manifestations, including the accumulation of massive numbers
      of CD4-CD8- T lymphocytes. In vivo chimera experiments have shown that the Ipr
      mutation is functionally expressed in both T and B cells. When lethally
      irradiated Ipr mice were given a combination of normal and Ipr bone marrow, only
      Ipr-derived B cells produced autoantibodies and only Ipr-derived T cells
      hyperproliferated. In contrast, analogous experiments with gld mice showed that
      the co-infusion of normal bone marrow greatly reduced autoantibody production.
      These results indicated that the gld B cell defect was extrinsic to those cells
      producing autoantibodies, in agreement with the recent molecular data showing
      that the normal gene products of the Ipr and gld loci form an interacting
      receptor-ligand pair. In the present study, we have extended our functional
      studies with gld mice using T cell-marked congenic donors. Lymphadenopathy was
      reduced three- to fourfold in gld mice given a combination of congenic normal and
      gld bone marrow compared with mice given gld bone marrow alone, and the absolute
      number of CD4-CD8- T cells was reduced by a factor of 7. Surprisingly, the
      residual CD4-CD8- T cells present in the mixed chimeras were derived entirely
      from the gld donor marrow. This suggests that the gld mutation results in both an
      extrinsic and intrinsic defect in T cells.

PMID- 7527825
TI  - Inhibition of human immunodeficiency virus type 1 replication in cytokine
      stimulated monocytes/macrophages by combination therapy.
AB  - Combination regimens against human immunodeficiency virus type 1 (HIV-1) were
      studied in granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated
      monocyte/macrophage cultures. Regimens included those that inhibited the same
      target (reverse transcriptase) or multiple targets. Treatment conditions assessed
      efficacy during prophylaxis and ongoing infection. Drugs included zidovudine,
      didanosine, nevirapine, foscarnet, pyridinone, the protease inhibitor RO31-8959
      (also known as saquinavir), interferon-alpha A, the Tat inhibitor RO24-7429, and
      N-butyl-deoxynojirimycin. Two-, three-, and four-drug combinations were tested.
      Drugs were tested at individually inhibitory concentrations of IC99, IC95, IC75,
      and IC50. All prophylactic regimens prevented HIV-1 replication at IC99. As drug
      concentrations were reduced, differences among the regimens became apparent.
      Regimens that acted at both single and multiple targets were effective in
      prophylactic settings and less so in acute infection. In ongoing infections, only
      modest reductions in viral replication were seen, even at IC99.

PMID- 7527823
TI  - The growth response to IL-7 during normal human B cell ontogeny is restricted to
      B-lineage cells expressing CD34.
AB  - The growth of human B cell precursors can be supported by bone marrow (BM)
      stromal cells and IL-7, but the identity of the responding population is unknown.
      In the current study, we examined the growth characteristics of FACS-purified
      CD10+/CD34+/cytoplasmic mu- pro-B cells and CD10+/CD34-/cytoplasmic mu+ pre-B
      cells in an IL-7/BM stromal cell-dependent culture. Our results show that pro-B
      cells proliferate, whereas pre-B cells do not. Pro-B cell growth was dependent
      upon direct contact with BM stromal cells, because no growth occurred when pro-B
      cells were suspended in transwells above a BM stromal cell monolayer in the
      presence of IL-7. IL-7-stimulated pro-B cells partially differentiated into a pre
      B cell population, on the basis of the loss of CD34 and terminal deoxynucleotidyl
      (TdT) expression, and the acquisition of cytoplasmic mu heavy chains. Examination
      of platelet endothelial cell adhesion molecule-1/CD31 expression on B cell
      precursors revealed a bimodal distribution: CD34+ pro-B cells exhibited a high
      density pattern and CD34- pre-B cells exhibited a low density pattern. The IL-7
      induced differentiation of pro-B cells into pre-B cells included a shift from
      high CD31 to low CD31 expression. Interestingly, pro-B and pre-B cells expressed
      comparable levels of IL-7R, as determined by flow cytometry, even though pre-B
      cells were nonresponsive to IL-7 stimulation. Our collective results show that
      human pro-B cells require both IL-7 and direct contact with BM stromal cells to
      undergo proliferation and partial differentiation into the pre-B cell stage,
      whereas pre-B cells are nonresponsive to IL-7 and require other signals for their
      survival and growth.

PMID- 7527824
TI  - CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell
      proliferation, cytokine production, and generation of CTL.
AB  - Signals initiated through both the TCR complex and CD28 are required for optimal
      activation of T lymphocytes. Recently, it has been demonstrated that CD28
      interacts with two different ligands, designated CD80 (B7/B7-1) and CD86 (B70/B7
      2). We have produced stable transfectants that express CD80, CD86, or both
      ligands and have examined their ability to costimulate T cell proliferation,
      cytokine production, and the generation of CTL. When we used small, resting human
      peripheral blood T cells as responders, both CD80 and CD86 transfectants
      efficiently costimulated anti-CD3 mAb-induced proliferation and the secretion of
      IL-2 and IFN-gamma. Additionally, both CD80 and CD86 transfectants were able to
      generate functional CTL. The magnitude and kinetics of these responses were
      similar, which indicates that both ligands provide efficient costimulatory
      signals. Because many APCs coexpress both CD80 and CD86, we compared the ability
      of anti-CD80 and anti-CD86 mAbs to inhibit allogeneic MLR stimulated with B
      lymphoblastoid cell lines and showed that it is necessary to inhibit interactions
      with both ligands to optimally block CD28-dependent proliferation. Given the
      limited homology of CD80 and CD86, it was surprising that the binding of CD28-Ig
      fusion protein to CD80 and that to CD86 transfectants were essentially
      indistinguishable. Binding of CTLA-4-Ig fusion protein to both transfectants also
      was quite similar, but was of higher affinity than CD28-Ig binding. Results from
      these studies indicate that both CD80 and CD86 are potent and similar
      costimulators of T lymphocytes. Therefore, the role of CD80 and CD86 in an immune
      response may be determined primarily by their differential expression on APC.

PMID- 7527826
TI  - Infection with Pseudomonas cepacia in chronic granulomatous disease: role of
      nonoxidative killing by neutrophils in host defense.
AB  - Pseudomonas aeruginosa and Pseudomonas cepacia are catalase-producing bacteria,
      but only P. cepacia causes infections in patients with chronic granulomatous
      disease (CGD). The in vitro killing of P. aeruginosa and P. cepacia by
      polymorphonuclear leukocytes (PMNL) from patients with CGD and from healthy
      adults was assessed. Of 6 patients with CGD who developed severe infections with
      P. cepacia, 4 died. PMNL from the 2 survivors and 6 other patients with CGD
      killed P. aeruginosa strains efficiently and P. cepacia strains poorly. PMNL from
      2 patients with autosomal recessive CGD and from 2 carriers for X-linked CGD
      killed P. cepacia intermediately between normal controls and patients with X
      linked CGD. When superoxide anion and hydrogen peroxide were scavenged with
      superoxide dismutase and catalase, normal PMNL killed P. aeruginosa but not P.
      cepacia. Thus, P. cepacia, but not P. aeruginosa, is a pathogen in patients with
      CGD, because it resists neutrophil-mediated nonoxidative bactericidal effects.

PMID- 7527827
TI  - Confirmation of hepatitis C virus transmission through needlestick accidents by
      molecular evolutionary analysis.
AB  - To document the transmission of hepatitis C virus (HCV) through needlestick
      accidents, 3 health workers who acquired HCV through such accidents and their HCV
      donor patients were studied using molecular evolutionary analysis based on the
      HCV E2 region. At least six clones were sequenced from each subject. Nucleotide
      substitutions were estimated by the six-parameter method, and a phylogenetic tree
      was constructed by the neighbor-joining method. HCV isolates from the donor
      patient and the recipient were nested in one monophyletic cluster; this
      clustering was confirmed to be statistically significant by bootstrap analysis.
      The nucleotide divergence among the isolates from the recipient was always
      smaller than that from the donor, supporting the notion that the direction of
      transmission was from the donor to the recipient. These findings provide
      evidence, at a molecular evolutionary level, that HCV was transmitted through
      needlestick accidents.

PMID- 7527829
TI  - Human neutrophils are selectively activated by independent ligation of the
      subunits of the CD11b/CD18 integrin.
AB  - The yeast cell wall preparation zymosan is a particulate stimulus for human
      neutrophils (PMNs). Unopsonised zymosan particles bind to the PMN CD11b/CD18
      integrin and are phagocytosed, leading to activation of the 5-lipoxygenase
      pathway and release of the lipid chemotaxin leukotriene B4 (LTB4). Specific
      monoclonal antibodies (mAbs) to CD11b and to CD18 were used in the present study
      to evaluate the contribution of each chain to these processes. All four anti-CD18
      mAbs but none of five anti-CD11b mAbs dose-dependently blocked PMN phagocytosis
      of zymosan. Nevertheless, all anti-CD11b mAbs and all anti-CD18 mAbs
      significantly inhibited zymosan-stimulated LTB4 release in a dose-dependent
      manner. In addition, there was a dose-dependent stimulation of LTB4 release
      resulting from the specific ligation and cross-linking of either chain of the
      integrin heterodimer. Thus zymosan-stimulated LTB4 release is initiated by
      signals from both chains of the CD11b/CD18 integrin, whereas only CD18 is
      essential for phagocytosis.

PMID- 7527828
TI  - Association of hepatitis C virus infection with false-positive tests for
      syphilis.
AB  - The prevalence of false-positive reactions for syphilis (reactive rapid plasma
      reagin [RPR] test and nonreactive fluorescent treponemal antibody absorption [FTA
      ABS] test) among patients at sexually transmitted disease (STD) clinics was
      assessed to evaluate the association between false-positive RPR reactions and
      hepatitis C virus (HCV) infections. Among 2672 patients, 400 (15.0%) had
      antibodies to HCV (anti-HCV) and 254 (9.5%) had a reactive RPR test. Of the 254
      reactive RPR tests, 231 (90.1%) were also positive by FTA-ABS, leaving 23 false
      positive RPR reactions. After excluding the 231 patients with positive FTA-ABS
      tests, false-positive RPR tests were found in 9 (2.7%) of 330 anti-HCV-positive
      patients compared with 14 (0.6%) of 2154 anti-HCV-negative participants (relative
      risk, 4.5; 95% confidence interval, 1.9-10.9; P = .0017). These data demonstrate
      that HCV infection is associated with false-positive RPR test results. However,
      because of the high prevalence of syphilis among STD patients, the RPR test
      remains a strong indicator of syphilis in this setting.

PMID- 7527830
TI  - Kinetics of macrophage subpopulations and expression of monocyte chemoattractant
      protein-1 (MCP-1) in bleomycin-induced lung injury of rats studied by a novel
      monoclonal antibody against rat MCP-1.
AB  - We investigated the kinetics of macrophage subpopulations and the expression of
      monocyte chemoattractant protein 1 (MCP-1) in a rat model of bleomycin-induced
      lung injury. Rat macrophage subpopulations were examined by immunohistochemistry
      using various anti-rat macrophage monoclonal antibodies (mAbs) and their
      proliferative capacity by [3H]thymidine (3HTdR) autoradiography. To detect the
      localization of expressed MCP-1, we generated an mAb against rat MCP-1 for
      immunohistochemical staining. Expression of MCP-1 messenger RNA (mRNA) was
      detected by Northern blot hybridization. Shortly after intratracheal instillation
      of bleomycin, the number of exudate macrophages recognized by mAb TRPM-3
      increased in the injured lungs, peaked 3 days later, and decreased thereafter,
      whereas tissue macrophages identified by mAb ED2 increased slowly and peaked 2
      weeks after instillation. Northern blot analysis disclosed that the expression of
      MCP-1 mRNA in the lung was most prominent 1 day after instillation and declined
      thereafter, preceding the numerical change of the TRPM-3-positive exudate
      macrophages. Immunohistochemistry with anti-rat MCP-1 revealed that the main
      sources of MCP-1 production were alveolar and interstitial macrophages and
      polymorphonuclear leukocytes. Based on these results, MCP-1 produced by
      polymorphonuclear leukocytes and by alveolar and interstitial macrophages is
      thought to induce the infiltration of blood monocytes, and infiltrated exudate
      macrophages produce MCP-1 to enhance subsequent accumulation of macrophages. In
      contrast, the expression of MCP-1 did not correlate with the numerical changes of
      the ED2-positive macrophages.

PMID- 7527831
TI  - Distinct patterns of nitric oxide production in hepatic macrophages and
      endothelial cells following acute exposure of rats to endotoxin.
AB  - Hepatic macrophages and endothelial cells play an important role in the clearance
      of endotoxin from the portal circulation. These cells are activated by endotoxin
      to release reactive mediators including superoxide anion, hydrogen peroxide, and
      nitric oxide, which have been implicated in hepatic inflammation and tissue
      injury. In the present studies we analyzed mechanisms regulating the production
      of nitric oxide by hepatic macrophages and endothelial cells following in vivo
      exposure to endotoxin. Rats were injected intravenously with Escherichia coli
      lipopolysaccharide (LPS, 5 mg/kg). Cells were isolated from the animals 48 h
      later by in situ perfusion of the liver with collagenase and pronase followed by
      differential centrifugation and centrifugal elutriation. We found that
      macrophages and endothelial cells from both untreated and endotoxin-treated rats
      readily synthesized nitric oxide following in vitro stimulation with interferon
      gamma (IFN-gamma) and LPS alone and in combination. This response was dependent
      on l-arginine and was blocked by two nitric oxide synthase inhibitors, NG
      monomethyl-l-arginine and l-canavanine. Macrophages produced more nitric oxide in
      response to LPS or LPS plus IFN-gamma than endothelial cells. In addition, nitric
      oxide production by both cell types in response to LPS plus IFN-gamma was
      increased after treatment of rats with endotoxin. Macrophages appeared to be more
      sensitive than endothelial cells to the in vivo effects of this inflammatory
      stimulus. Northern and Western blot analysis demonstrated that nitric oxide
      production by macrophages and endothelial cells in response to LPS plus IFN-gamma
      was due to increased expression of an inducible form of nitric oxide synthase
      (iNOS) mRNA and protein. Using fluorescence image analysis, iNOS protein was
      found to be localized in the cytoplasm of the cells. Treatment of rats with
      endotoxin was associated with increased expression of iNOS protein in the
      macrophages. The phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) also
      stimulated nitric oxide production by macrophages and endothelial cells from
      endotoxin-treated rats, although not as effectively as LPS and IFN-gamma.
      Macrophages were more responsive than endothelial cells to TPA. Furthermore,
      depletion of the cells of glutathione using buthionine sulfoximine had no major
      effect on nitric oxide production by macrophages but resulted in small but
      significant inhibition in endothelial cells. This suggests that this sulfhydryl
      containing tripeptide does not regulate intracellular levels of reactive nitrogen
      intermediates in activated macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7527833
TI  - Human cytomegalovirus structural proteins.

PMID- 7527832
TI  - Production of nitric oxide and peroxynitrite in the lung during acute
      endotoxemia.
AB  - Nitric oxide is a short-lived cytotoxic mediator that has been implicated in the
      pathogenesis of endotoxin-induced tissue injury and septic shock. In the present
      studies we determined whether this mediator is produced in the lung during acute
      endotoxemia. We found that intravenous injection of rats with bacterially derived
      lipopolysaccharide (LPS), a condition that induces acute endotoxemia, caused a
      time-dependent increase in inducible nitric oxide synthase (iNOS) mRNA expression
      in the lung, which reached a maximum after 24 h. This was correlated with nitric
      oxide production in the lung as measured by electron paramagnetic spin trapping,
      which was detectable within 6 h. Alveolar macrophages (AMs) and interstitial
      macrophages (IMs) isolated from rats 6-12 h after induction of acute endotoxemia
      were also found to exhibit increased nitric oxide production in response to in
      vitro stimulation with interferon-gamma (IFN-gamma) and LPS measured by nitrite
      accumulation in the culture medium. The effects of acute endotoxemia on nitric
      oxide production by these cells were, however, transient and returned to control
      levels by 24 h in AMs and 36 h in IMs. Interestingly, although nitrite
      accumulation in the culture medium of IMs isolated 48 h after induction of acute
      endotoxemia and stimulated with low concentrations of IFN-gamma and LPS was
      reduced, when compared with cells from control animals, these cells, as well as
      AMs, continued to express high levels of iNOS protein and mRNA. This was
      correlated with increased peroxynitrite production by the cells. Peroxynitrite
      has been shown to act as a nitrating agent and can generate nitrotyrosine
      residues in proteins. Using a specific antibody and immunohistochemistry, we
      found evidence of nitrotyrosine residues in sections of lungs 48 h after
      treatment of rats with endotoxin. These data suggest that nitric oxide produced
      by IMs and AMs can react with superoxide anion to form peroxynitrite. Taken
      together, the present studies demonstrate that AMs and IMs are activated
      following acute endotoxemia to produce reactive nitrogen intermediates and that
      both cell types contribute to inflammatory responses in the lung.

PMID- 7527835
TI  - Comparison of the expression and phosphorylation of the non-structural protein
      NS2 of three different orbiviruses: evidence for the involvement of an ubiquitous
      cellular kinase.
AB  - The non-structural protein NS2 of epizootic haemorrhagic disease (EHD),
      bluetongue (BT) and African horsesickness (AHS) viruses has each been expressed
      to high levels using a baculovirus vector gene expression system. It was found
      that the recombinant baculovirus-expressed EHDV NS2 protein was resolved as a
      doublet following PAGE. Peptide mapping of these protein bands indicated that
      they were identical. The difference in the sizes of the NS2 protein bands could
      not be attributed to the phosphorylation of NS2 or other posttranslational
      modification such as N-glycosylation and remains obscure. The EHDV, BTV and AHSV
      baculovirus-expressed NS2 proteins were all phosphorylated in vitro without the
      addition of an exogenous kinase. An unphosphorylated form of EHDV NS2, obtained
      by expressing the NS2 gene as a fusion protein in Escherichia coli cells, could
      be phosphorylated in vitro by a protein kinase associated with the cytoplasm of
      insect cells. The phosphorylated version of this protein was found to be
      significantly less efficient in binding ssRNA, compared to the unphosphorylated
      version.

PMID- 7527834
TI  - Interleukin-10 inhibits initial reverse transcription of human immunodeficiency
      virus type 1 and mediates a virostatic latent state in primary blood-derived
      human macrophages in vitro.
AB  - Interleukin-10 (IL-10), a product of T lymphocytes, B cells and macrophages,
      participates in Th-2 immune responses and modulates macrophage functions
      including possible interactions with pathogens. We have found that Chinese
      hamster ovary cell-derived human recombinant (hr) IL-10 inhibits human
      immunodeficiency virus type 1 strains Ada and Ba-L (HIV-1ADA and HIV-1Ba-L)
      replication in primary tissue culture-derived macrophages in a dose-dependent
      manner. Inhibition by IL-10 treatment (> 5 U/ml) was effective 72 h before or 24
      h after infection and cytokine activity blocked by anti-hrIL-10 antibody (19F1),
      or lost after heat inactivation of IL-10. Viral production was measured by
      determining p24 and reverse transcriptase levels while reverse transcription
      kinetics for the long terminal repeat (LTR) and gag were assessed at timed
      intervals after infection and quantified by 32P end-labelling. IL-10 inhibited
      early steps of infection without modulating cell surface CD4+ levels. The onset
      of LTR reverse transcription was delayed by 4 to 8 h and the number of LTR
      transcripts was decreased by 77% at 24 h and by 87% 48 h after infection. IL-10
      effects were reversible; after cytokine washout, cells treated before infection
      showed lower levels of virus compared with those treated after infection. IL-10
      biological activity was confirmed in three virus-independent assays. These
      results demonstrate IL-10 decreases HIV-1 reverse transcription upon macrophage
      infection and subsequently mediates viral latency in vitro. Therefore, IL-10 may
      be involved in the effective control of HIV-1-infected macrophages in vivo.

PMID- 7527836
TI  - The NS1 protein of tick-borne encephalitis virus forms multimeric species upon
      secretion from the host cell.
AB  - Flaviviruses elicit a humoral immune response to two virus-encoded, membrane
      associated glycoproteins. One is the major virion surface envelope protein (E),
      which is recognized by antibody, whereas the other is a secreted, heavily
      glycosylated non-structural protein (NS1). Inoculation with either protein can
      give rise to a protective immune response, as can the passive transfer of E and
      NS1 monospecific monoclonal antibodies. Experiments reported here demonstrate
      that the secreted form of NS1, whether from cells infected with tick-borne
      encephalitis virus (TBEV) or from cells infected with a defective recombinant
      adenovirus containing the NS1 gene, occurs chiefly as a pentamer or hexamer and
      occasionally as a decamer or dodecamer. Intracellular forms of this protein
      however occur only as dimers. The higher M(r) forms secreted from the cell are
      exquisitely sensitive to detergent, suggesting they are held together by
      hydrophobic bonds. Both intracellular and extracellular forms of the dimer can be
      dissociated by heat, but at different temperatures. Unlike similar proteins from
      mosquito-borne viruses. NS1 from TBEV-infected cells cannot be dissociated at
      ambient temperatures by extremes of pH. Studies on the antigenic structure of
      this protein show it to have several highly conserved epitopes, confirming
      similar earlier conclusions from amino acid sequence analyses.

PMID- 7527839
TI  - Characterization of a secreted form of measles virus haemagglutinin expressed
      from a vaccinia virus recombinant.
AB  - The measles virus (MV) haemagglutinin (HA) is a class 2 glycoprotein by means of
      which the virus particle attaches to the host cell receptor. We have previously
      expressed this glycoprotein as a vaccinia recombinant virus and have shown that
      the HA glycoprotein synthesized is indistinguishable from that coded by MV. In
      the present study, we report that in RK13 cells a soluble form (sHA) of the HA is
      secreted into the medium. We show by SDS-PAGE and sucrose density gradient
      centrifugation that the sHA is a dimer and is smaller than the cell-associated
      form. Using a variety of inhibitors the production of sHA was shown to be a late
      event, probably occurring at the membrane; only fully glycosylated molecules were
      found in sHA. Finally, we demonstrate that sHA retains its antigenicity with
      conformation-dependent MAbs and its receptor recognition function. We conclude
      that sHA is a valuable tool for use in studies of the structure and function of
      the MV HA glycoprotein.

PMID- 7527837
TI  - Functional reconstitution in lipid vesicles of influenza virus M2 protein
      expressed by baculovirus: evidence for proton transfer activity.
AB  - The influenza virus M2 protein was expressed from a recombinant baculovirus in
      Spodoptera frugiperda Sf9 cells, purified and reconstituted into artificial
      membrane vesicles. The specific inhibitor amantadine overcame the toxic activity
      of the protein and boosted the rate of M2 synthesis by a factor of 10, allowing
      yields of about 1 mg of purified M2 protein per g of Sf9 cells. M2 protein
      expressed in this system was phosphorylated and palmitoylated and displayed
      properties similar to the authentic virus protein. Purified wild-type M2 protein
      and an amantadine-resistant mutant M2 (M2 delta) with a deletion in the trans
      membrane domain (amino acids 28 to 31) were incorporated into lipid vesicles,
      which were loaded with the fluorescent pH indicator pyranine. On imposition of an
      ionic gradient, M2 caused a decrease in intravesicular pH, which was susceptible
      to inhibition by 0.1 to 1 microM-rimantadine or N-ethyl-rimantadine. M2 delta
      behaved similarly but exhibited the expected drug resistance. These experiments
      indicate that isolated M2 functions as an ion channel and demonstrates in vitro
      M2-mediated proton translocation.

PMID- 7527838
TI  - Neutralization escape mutants of type A influenza virus are readily selected by
      antisera from mice immunized with whole virus: a possible mechanism for antigenic
      drift.
AB  - It is not fully understood how antigenic drift of the haemagglutinin of type A
      influenza virus in man occurs in the presence of the expected polyclonal antibody
      response to the five antigenic sites, A to E. Here we show that 12% (11/92) of
      sera from mice which had mounted a secondary immune response to inactivated
      influenza virus were able to select escape mutants. No escape mutant was selected
      with serum from nonimmunized mice (0/65). Selection required only a single
      passage, and escape mutants were identified by their reaction with monoclonal
      antibodies (MAbs); all but one had altered reactivity at site A. Most of the site
      A escape mutants (7/10) were conventional in character and did not react in
      haemagglutination-inhibition (HI) or neutralization assays with the identifying
      MAb. The HA genes of three of these were part sequenced and had a predicted
      single amino acid substitution (Gly-144-->Glu) in site A. The other escape
      mutants (3/10) had a small (2-fold) reduction in HI and neutralization to the
      site A MAb, but no amino acid substitution in site A. The final mutant was a
      conventional site B escape mutant. To model antisera which selected escape
      mutants, we constructed 'pseudo-immune sera' using mixtures of two neutralizing
      MAbs in which the first MAb was held at a constant high concentration (1000
      HIU/ml). Escape mutants could be selected to the first MAb when the titre of the
      second MAb was reduced to a low but still inhibiting concentration (1 to 3
      HIU/ml). Mixtures of three MAbs also selected escape mutants with similar
      facility provided that the second and third MAbs were reduced to a similar low
      concentration. Thus it is possible that the ability of an antiserum to select
      escape mutants is due to the neutralizing antibody response being biased to an
      epitope/cross-reacting epitopes within a single antigenic site. However, when
      escape mutants were reacted in HI assay with their selecting antiserum, the
      maximum difference from the titre with wt virus was 75%. The findings of this
      study may be relevant to the understanding of antigenic drift in type A human
      influenza virus, and to immune-driven antigenic variation in other virus
      infections.

PMID- 7527840
TI  - A modified hepatitis B virus surface antigen with the receptor-binding site for
      hepatocytes at its C terminus: expression, antigenicity and immunogenicity.
AB  - A modified hepatitis B virus (HBV) surface antigen, the SA-28 protein, was
      constructed and expressed by recombinant vaccinia virus in mammalian cells. This
      protein was composed of a PreS1 region-derived peptide (amino acids 21 to 47)
      that contained the hepatocyte receptor-binding site, joined to the C terminus of
      the major S protein at amino acid position 223. This modified surface antigen
      could be efficiently assembled into particles with a density of 1.23 g/ml and
      could be secreted from several mammalian cell lines. The results of
      immunoprecipitation revealed that the SA-28 protein was recognized by both the
      anti-S protein antibody and the anti-PreS1 antibody. A strong antibody response,
      against both the S protein and PreS1 epitopes, was induced in BALB/c mice
      immunized by the SA-28 particles indicating good immunogenicity. These results
      suggested that the HBV surface antigen consisting of the SA-28 protein could be a
      promising candidate as a new HBV vaccine with higher efficacy.

PMID- 7527841
TI  - A Drosophila receptor tyrosine phosphatase expressed in the embryonic CNS and
      larval optic lobes is a member of the set of proteins bearing the "HRP"
      carbohydrate epitope.
AB  - Recent studies have defined several cell surface glycoproteins expressed in the
      developing nervous system of insect embryos that may be involved in axon
      outgrowth and guidance processes. These glycoproteins include the fasciclins and
      a group of receptor-linked protein tyrosine phosphatases (R-PTPs). In embryos,
      the fasciclins are localized to axonal subsets, while the R-PTPs appear to be
      expressed on most or all CNS axons. To identify other neuronal cell surface
      glycoproteins in the Drosophila embryo, we have taken a biochemical approach.
      This is based on the observation that antisera against horseradish peroxidase
      (HRP) recognize a carbohydrate epitope that is selectively expressed in the
      insect nervous system. A large number of neuronal glycoproteins (denoted "HRP
      proteins") apparently bear the HRP carbohydrate epitope. We have used polyclonal
      anti-HRP antibodies to purify these proteins from Drosophila embryos, and have
      obtained protein sequences from seven HRP protein bands. These data define three
      major HRP proteins as neurotactin, fasciclin I, and an R-PTP, DPTP69D. Western
      blotting data suggest that fasciclin II, neuroglian, DPTP10D, and DPTP99A are
      also HRP proteins. We show that DPTP69D, like the previously characterized R
      PTPs, is localized to CNS axons in the embryo. In third instar larvae, DPTP69D
      expression is restricted to subsets of neuronal processes in the brain, ventral
      nerve cord, and eye disk. In the optic lobes, DPTP69D is localized to the
      neuropils of the lamina and medulla, and to an array of parallel thick bundles
      that may be the transmedullary fibers of the developing lobula complex.

PMID- 7527842
TI  - Inhibition of nitric oxide synthase does not impair spatial learning.
AB  - Nitric oxide (NO), a putative intercellular messenger in the CNS, may be involved
      in certain forms of synaptic plasticity and learning. This article reports a
      series of experiments investigating the effects of N omega-nitro-L-arginine
      methyl ester (L-NAME) upon various forms of learning and memory in the watermaze.
      L-NAME (75 mg/kg, i.p., sufficient to bring about > 90% inhibition of NO
      synthesis in brain) produced an apparent impairment in spatial learning when
      given to naive rats during acquisition (3 d, six training trials per day). This
      impairment was dose related, stereoselective, and attenuated by coadministration
      of L-arginine. A second study showed that L-NAME did not affect the retention of
      a previously learned spatial task. In addition, in a visual discrimination task,
      the rate at which criterion levels of performance were reached was unaffected by
      L-NAME. Thus, inhibition of NO synthase may cause a selective impairment of
      spatial learning without effect upon retention. However, analysis of the early
      training trials of the visual discrimination task revealed significantly elevated
      escape latencies in the L-NAME-treated rats, suggesting that inhibition of NO
      synthase may have more general effects. As normal rats learn the spatial task
      very rapidly, the possibility arises that the apparent deficit in learning is due
      to a disruption of some process other than learning per se. A further series of
      experiments investigated this possibility. L-NAME was found not to impair the
      learning of a new platform position in the same spatial environment.
      Surprisingly, L-NAME also had no effect on spatial learning in a second watermaze
      located in a novel spatial environment by rats well practiced with all aspects of
      watermaze training. Finally, L-NAME had no effect on spatial learning in naive
      rats trained with just one trial per day. Thus, systemic injection of an NO
      synthase inhibitor impairs behavioral performance in two tasks during their
      initial acquisition, but the basis of this functional disruption is unlikely to
      be due to any direct effect upon the mechanisms of spatial learning.

PMID- 7527843
TI  - Inhibition of nitric oxide synthase does not prevent the induction of long-term
      potentiation in vivo.
AB  - Nitric oxide (NO), a putative intercellular messenger in the CNS, may be involved
      in certain forms of synaptic plasticity and learning. This article reports a
      series of experiments investigating whether an inhibitor of NO synthase, N omega
      nitro-L-arginine methyl ester (L-NAME), affects long-term potentiation (LTP) in
      vivo, as the results of recent in vitro experiments would predict. L-NAME, given
      as an acute injection at a dose sufficient to inhibit hippocampal NO synthase (>
      90%), had no effect on perforant path-dentate gyrus LTP induced by a strongly
      suprathreshold tetanus, but appeared to impair LTP induced by a weak near
      threshold tetanus that may be more physiologically relevant. However, subsequent
      studies revealed that chronic L-NAME treatment (> 95% inhibition of NO synthase)
      had no effect upon LTP induction, and that acute (but not chronic) treatment
      resulted in a gradual but significant reduction in nontetanized baseline field
      potentials. The baseline shift appeared to be of a magnitude sufficient to
      account for the apparent impairment of weak tetanus-induced LTP. This possibility
      was further examined in a two-hemisphere experiment in which the time course of
      changes in the field EPSP of the nontetanized pathway served as the within
      subject control for the tetanized pathway. No impairment of LTP induction was
      observed; indeed, if anything, there was a trend for greater potentiation with L
      NAME. Because NO has also been implicated in the control of vasodilation, the
      effect of L-NAME on cerebrovascular function was also investigated. Peripheral
      blood pressure was significantly increased by L-NAME at the same dose that
      affected the field EPSP. Local cerebral glucose utilization was unchanged, while
      local cerebral blood flow decreased significantly in various brain regions,
      including the hippocampus, indicating an uncoupling of cerebral metabolism and
      blood flow. Thus, while NO synthase inhibition does not appear to limit the
      induction of LTP in vivo, it does reduce the size of baseline field EPSPs and
      affect local cerebrovascular function.

PMID- 7527844
TI  - Calcium-activated release of nitric oxide and cellular distribution of nitric
      oxide-synthesizing neurons in the nervous system of the locust.
AB  - Nitric oxide (NO) is generated by a Ca2+/calmodulin-activated NO synthase and
      diffuses as a short-lived transcellular messenger through the plasma membrane.
      This study investigates the neurochemistry and anatomical distribution of NO
      releasing cells in the CNS of the locust. Ca2+/calmodulin-activated NO synthase
      is responsible for fixation-sensitive NADPH diaphorase (NADPHd) activity in cell
      homogenates of the nervous system. Therefore, neurons expressing NO synthase were
      detected by NADPHd histochemistry performed in whole-mounts. The anatomical
      screening revealed fewer than 1% NADPHd-positive cells in the ventral nerve cord,
      some of which were single potentially identifiable neurons, and groups of cell
      bodies in several regions of the cerebral ganglion. A prominent feature of the
      histochemical survey in the cerebral ganglion is a group of 45 intensely stained
      cells innervating the olfactory neuropil of the antennal lobe. A basic
      requirement for identifying NO as a messenger molecule is the Ca(2+)-dependent
      release during nerve cell depolarization. With a sensitive photometric assay we
      demonstrated that dissociated cells from brain areas rich in NADPHd-positive
      neurons release NO after stimulation by agents elevating cytoplasmic Ca2+ levels
      and by the excitatory neurotransmitter acetylcholine. The combined anatomical and
      biochemical experiments therefore provide firm evidence that NO is a messenger
      molecule released in the CNS of the locust. Since locust neurons can be readily
      grown in primary culture, NO-induced elevations of CGMP levels and other signal
      transduction mechanisms in target cells will also be amenable to a cellular
      analysis.

PMID- 7527845
TI  - Cyclic AMP and synaptic activity-dependent phosphorylation of AMPA-preferring
      glutamate receptors.
AB  - Several studies have suggested that the function of glutamate receptor channels
      can be regulated by protein phosphorylation. Furthermore, a basal level of
      phosphorylation may be necessary to maintain receptor function. Little is known,
      however, about the phosphorylation state of glutamate receptor channels in
      neurons and how it is regulated by synaptic activity. In this study, we have
      investigated the phosphorylation of the AMPA-preferring glutamate receptor
      subunit GluR1 in cortical neurons in primary culture. These neurons elaborate
      extensive processes, form functional synapses, and exhibit spontaneous 4-8 sec
      bursts of synaptic activity every 15-20 sec. In cultures in which this synaptic
      activity was suppressed by tetrodotoxin and MK-801, the GluR1 protein was
      phosphorylated on serine residues within a single tryptic phosphopeptide, as
      determined by phosphoamino acid analysis and phosphopeptide mapping. This same
      peptide was basally phosphorylated in recombinant GluR1 receptors transiently
      expressed in human embryonal kidney 293 cells. Treatment of these synaptically
      inactive cortical neurons with the adenylyl cyclase activator forskolin resulted
      in a robust increase in phosphorylation on serine residues on a phosphopeptide
      distinct from the basally phosphorylated peptide. Again, this same phosphopeptide
      was observed in recombinant GluR1 receptors isolated from 293 cells coexpressing
      the catalytic subunit of cAMP-dependent protein kinase. Spontaneous synaptic
      activity in cultures of cortical neurons resulted in a consistent, rapid (within
      10-30 sec) increase in phosphorylation on serine and threonine residues.
      Interestingly, these phosphopeptides were also phosphorylated when neurons from
      inactive cultures were stimulated with phorbol esters, which activate protein
      kinase C. These results indicate that AMPA receptors containing the GluR1 subunit
      may be regulated by extracellular signals working through the cAMP second
      messenger system as well as by synaptic activity, possibly acting through protein
      kinase C. Such regulation by protein phosphorylation may be involved in short
      term changes in synaptic efficacy thought to involve the functional modulation of
      AMPA receptors.

PMID- 7527846
TI  - Nitric oxide synthase in Muller cells and neurons of salamander and fish retina.
AB  - Nitric oxide synthase (NOS) is the biosynthetic enzyme of the signaling molecule
      nitric oxide (NO). NO donors have been reported to modulate conductances in cell
      types throughout the retina, from photoreceptors to ganglion cells. Previously,
      NOS immunoreactivity has been reported in amacrine cells and cells within the
      ganglion cell layer. Here, we have examined the cellular localization of NOS in
      the retinas of salamander, goldfish, and catfish using both an affinity-purified
      antiserum to brain NOS and NADPH diaphorase (NADPHd) histochemistry. These
      markers indicate that an NOS-like enzyme is localized not only to presumptive
      amacrine cells but also, depending on the species, to photoreceptor ellipsoids,
      to somata within the ganglion cell layer, and to horizontal cells. In addition to
      these neurons, our results indicate that Muller cells, the radial glia of the
      retina, also contain an NOS-like enzyme. In support of this latter conclusion,
      cells morphologically similar to Muller cells were positive for NADPHd staining
      in all three species. In salamander, NOS-like immunoreactivity, NADPHd staining,
      and binding of anti-GFAP (a marker for glia) were localized to cells that were
      morphologically indistinguishable from Muller cells. In goldfish, reactivity to
      both anti-NOS and anti-vimentin (a marker for glia) colocalized to radial
      processes extending through the inner retina to the inner limiting membrane.
      These observations are the first to indicate the presence of an NOS-like enzyme
      in Muller cells and suggest that these glia could be a ready source of NO for
      target neurons throughout the retina.

PMID- 7527847
TI  - The correlation between the distribution of the NK1 receptor and the actions of
      tachykinin agonists in the dorsal horn of the rat indicates that substance P does
      not have a functional role on substantia gelatinosa (lamina II) neurons.
AB  - The presence of substance P in primary afferents that terminate in the outer
      laminae of the spinal cord has led to considerable interest in the function of
      this neuropeptide in nociception. We have examined the actions of tachykinin
      agonists on the membrane potential of neurons in lamina II of a neonatal spinal
      cord slice preparation in vitro. Only 10.5% (n = 75) of these neurons showed any
      response to the application of a selective NK1 receptor agonist while 48.3% (n =
      60) of neurons in deeper dorsal horn laminae responded to this agonist. Lamina II
      neurons were equally insensitive to selective NK2 and NK3 agonists. Synaptic
      potentials evoked in lamina II neurons by peripheral nerve stimulation were
      similarly not altered by the NK1 agonist. Immunocytochemical studies using an
      antibody raised against the C-terminal of the NK1 receptor revealed that very few
      lamina II neurons express NK1 receptors, and this offers an explanation for our
      findings.

PMID- 7527848
TI  - Novel expression of the tyrosine hydroxylase gene requires both acidic fibroblast
      growth factor and an activator.
AB  - Substances found in the soluble extract of muscle can alter the differentiative
      fate of certain brain neurons in culture by triggering novel expression of the
      gene for the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH)
      (Iacovitti et al., 1989; Iacovitt, 1991). In this study, we demonstrate that TH
      induction in cultured noncatecholamine neurons from the mouse striatum requires
      the cooperative interaction of at least two substances found in muscle.
      Purification studies, combined with biological assay, revealed that one necessary
      component is acidic fibroblast growth factor (aFGF), and the other, an
      unidentified molecule(s) of < 10 kDa molecular weight that activated aFGF. Thus,
      muscle-derived aFGF, if incubated in the presence but not the absence of the < 10
      kDa fraction of muscle, induced a dose-dependent increase in the number of
      striatal neurons that novelly express TH. This expression was blocked by prior
      incubation and protein A precipitation of the factor with polyclonal antibodies
      to aFGF (1:200-1:1000). Similar to muscle-purified aFGF, commercial preparations
      of native bovine and human recombinant aFGF (0.1-100 ng/ml) were potent inducers
      of TH when coincubated with the < 10 kDa activator. In contrast, basic FGF
      produced little and FGF-7 no induction of TH. Unlike the unidentified activating
      agent in muscle, heparin (20-500 mU), a known activator of aFGF, did not
      potentiate the factor's TH-inducing activity. Nonetheless, heparatinase (100 mU)
      prevented TH induction by aFGF and its activator, indicating that binding of
      heparan sulfated proteoglycans is necessary for the effect.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7527849
TI  - Patterns of antibodies to hepatitis C virus and hepatitis C virus replication in
      children with chronic non-A, non-B hepatitis.
AB  - Antibodies to hepatitis C virus (HCV), investigated by second- and third
      generation assays, were detected in 74% of 43 children with chronic non-A, non-B
      hepatitis. The polymerase chain reaction identified HCV ribonucleic acid in 26
      (93%) of 28 seropositive and in 1 of 10 seronegative cases. Intermittent HCV
      ribonucleic acid positivity, suggesting low and fluctuating viremia, was frequent
      in younger patients.

PMID- 7527850
TI  - Treatment of alloimmune neonatal neutropenia with granulocyte colony-stimulating
      factor.
AB  - Despite numerous attempts to increase the neutrophil count of infants with
      alloimmune neonatal neutropenia, no therapy has been consistently effective. We
      describe two infants with alloimmune neutropenia who had a rapid and prolonged
      increase in neutrophil number after treatment with granulocyte colony-stimulating
      factor (G-CSF). Patient 1 had antibody directed against the neutrophil antigen
      NA2. He received three daily doses of G-CSF, and within 2 days his neutrophil
      count increased from 0.350 x 10(9) to 3.584 x 10(9)/L (350 to 3584/mm3). Despite
      cessation of treatment the neutrophil count remained in the normal range. Patient
      2 had antibody to the neutrophil antigen NA1, and received six daily doses of G
      CSF. Within 4 days his neutrophil count increased from 0.477 x 10(9) to 4.320 x
      10(9)/L (477 to 4320/mm3) and remained in the normal range for 11 days after the
      last dose of G-CSF. We recommend that treatment with G-CSF be considered for
      selected infants with alloimmune neutropenia.

PMID- 7527851
TI  - Inhibition of insulin release by a formamidine pesticide amitraz and its
      metabolites in a rat beta-cell line: an action mediated by alpha-2 adrenoceptors,
      a GTP-binding protein and a decrease in cyclic AMP.
AB  - We tested the hypothesis that the formamidine pesticide amitraz and its
      metabolites inhibit insulin release from a rat beta-cell line (RINm5F) by
      decreasing intracellular cyclic AMP levels and examined whether GTP-binding
      proteins were involved in the process. Amitraz and its active metabolite BTS27271
      (0.1-10 microM) inhibited insulin release that was induced by 100 microM of IBMX
      in a dose-dependent manner. Other metabolites of amitraz tested failed to inhibit
      insulin release. A potent and specific alpha-2 adrenoceptor agonist, medetomidine
      (0.1 microM), abolished the IBMX-induced insulin release. Amitraz, BTS27271 and
      medetomidine also decreased intracellular cyclic AMP concentrations that were
      elevated by IBMX administration. Moreover, all three drugs inhibited the insulin
      release stimulated by forskolin (1 microM), an adenylyl cyclase activator.
      Yohimbine (0.01, 0.1 and 1 microM), an alpha-2 adrenoceptor antagonist, prevented
      the inhibitory effect of amitraz and BTS27271 on insulin release, whereas
      prazosin (1 microM), an alpha-1 adrenoceptor antagonist, did not. Yohimbine, but
      not prazosin, also prevented the effect of amitraz, BTS27271 and medetomidine on
      IBMX-stimulated accumulation of cyclic AMP. Pretreatment of cells with PTX (0.1
      micrograms/ml) for 16 h, antagonized the effects of amitraz and BTS27271 on IBMX
      induced increase in insulin release. Thus, one mechanism by which amitraz and its
      metabolite BTS27271 decrease insulin release is by inhibiting adenylyl cyclase,
      an action mediated through a PTX-sensitive G-protein.

PMID- 7527852
TI  - Unmasking of activated histamine H3-receptors in myocardial ischemia: their role
      as regulators of exocytotic norepinephrine release.
AB  - We had previously found that histamine H3- receptors are negatively coupled to
      norepinephrine exocytosis in atrial tissue. We report here that in the presence
      of H1- and H2- receptor blockers, histamine significantly inhibits the
      tachycardia and norepinephrine release elicited by sympathetic nerve stimulation
      is isolated guinea pig hearts, an effect prevented by the H3 antagonist,
      thioperamide. Sympathetic nerve stimulation also caused a 1.5-fold increase in
      histamine overflow, which was insufficient to activate H3 receptors because
      thioperamide affected neither the tachycardia nor the norepinephrine release.
      Hence. We questioned whether H3 receptors become activated when adrenergic
      activity is greatly enhanced, as in myocardial ischemia. Guinea pig hearts
      underwent 10-min global ischemia. At reperfusion, norepinephrine exocytosis was
      markedly augmented and was associated with a 3.5-fold increase in histamine
      overflow. (R)alpha-methylhistamine, an H3 agonist, did not modify norepinephrine
      release, whereas thioperamide doubled it. Thus, in physiologic conditions,
      cardiac H3 receptors are quiescent, yet available for activation by exogenous
      ligands. In contrast, in the ischemic myocardium, H3 receptors appear to be fully
      activated by an endogenous ligand, probably histamine. Hence, cardiac H3
      receptors may play an important role by negatively modulating exocytotic
      norepinephrine release associated with ischemic states.

PMID- 7527853
TI  - Antitumor activity of a medium-chain triglyceride solution of the angiogenesis
      inhibitor TNP-470 (AGM-1470) when administered via the hepatic artery to rats
      bearing Walker 256 carcinosarcoma in the liver.
AB  - The antitumor effect of an angiogenesis inhibitor, TNP-470 (AGM-1470, 6-0-(N
      chloroacetylcarbamoyl)-fumagillol), administered via the hepatic artery in a
      medium-chain triglyceride (MCT) solution, in which TNP-470 is very stable, was
      examined in rats bearing Walker 256 carcinosarcoma in the liver. The MCT solution
      containing 0.1 mg of TNP-470 completely suppressed tumor growth after a single
      arterial injection, and the solutions containing 0.5 approximately 5 mg of TNP
      470 caused tumor regression function. These antitumor effects lasted for at least
      2 weeks. Moreover, the administration of the MCT solution containing 5 mg of TNP
      470 also caused remarkable regression of well-developed enlarged tumors 2 weeks
      after inoculation, indicating potential in the treatment of unresectable hepatic
      cancer. When the MCT solution containing radiolabeled TNP-470 was injected via
      the hepatic artery, the initial radioactivity in the tumor was 22 times that in
      the normal part of the liver and 5.7 times that in the tumor when an aqueous
      solution of radiolabeled TNP-470 was injected. Also, in the case of the MCT
      solution, the radioactivity in the tumor was maintained at a relatively high
      level for over 2 weeks after injection. These results indicate that the
      remarkable antitumor effect resulted from the selective delivery and prolonged
      retention of TNP-470 at the tumor site.

PMID- 7527854
TI  - Substance P N-terminal metabolites and nitric oxide mediate capsaicin-induced
      antinociception in the adult mouse.
AB  - The present investigation describes the antinociceptive effect of capsaicin in
      the acetic acid-induced abdominal stretch assay and its mediation by substance
      P(1-7) fragment [SP(1-7)] and nitric oxide (NO). When injected intrathecally 24
      hr before testing, SP(1-7) produced a dose-related decrease in the number of
      abdominal stretches induced by an i.p. injection of acetic acid. The
      antinociceptive effect of SP(1-7) (10 nmol) persisted for 62 hr after its
      injection, a time course that was similar to that produced by a dose of capsaicin
      (2.6 nmol) that produced an effect of similar magnitude. Antinociception induced
      by 10 nmol of SP(1-7) was completely reversed by coadministration of 10 nmol of D
      SP(1-7); the equivalent antinociception produced by capsaicin was reversed by as
      small a dose as 1 nmol of D-SP(1-7). The guanylate cyclase inhibitor, methylene
      blue, at a dose of 10 nmol, prevented both SP(1-7)- and capsaicin-induced
      antinociception. Capsaicin-induced, but not SP(1-7)-induced, antinociception was
      prevented by Nw-nitro-L-arginine methyl ester, an NO synthase inhibitor. This
      inhibition of capsaicin was reversed by coadministration of 120 nmol of L
      arginine. Reduced hemoglobin did not prevent capsaicin-induced antinociception.
      These findings suggest NO is produced and acts within capsaicin-sensitive primary
      afferent fibers in the dorsal spinal cord to mobilize substance P, resulting in N
      terminal induced-antinociception.

PMID- 7527856
TI  - Nonlinear pharmacokinetics of a recombinant human granulocyte colony-stimulating
      factor derivative (nartograstim): species differences among rats, monkeys and
      humans.
AB  - NTG is a human G-CSF derivative produced by Escherichia coli using gene
      engineering techniques. The dose dependency of NTG pharmacokinetics in rats and
      monkeys was examined and compared with that previously reported for humans. In
      all species, the total clearance decreased and the mean residence time was
      prolonged as the intravenously administered dose of NTG was increased. At higher
      doses, the clearance in each species approached a constant value. This suggests
      that both saturable and nonsaturable processes are involved in NTG elimination.
      At the lowest dose, the saturable process accounted for 57% to 76% of total
      clearance. The plasma concentration-time profiles of NTG in rats and monkeys were
      analyzed by nonlinear pharmacokinetic models which contained both linear and
      Michaelis-Menten type elimination from the central compartment. The Km and Vmax
      values in rat, about 240 pM and 40 pmol/hr/kg, respectively, were comparable to
      those in the monkey. On the other hand, the values in humans were smaller, about
      17% and 7%, respectively, than those in experimental animals. Therefore, the
      intrinsic clearance of saturable process (Vmax/Km) in humans was about one-half
      that in monkeys. To clarify the mechanism of the saturable clearance of NTG, the
      in vitro metabolic activities in rat bone marrow, spleen cells and peripheral
      leukocytes, which possess the G-CSF receptor, were determined. The metabolic
      activity of bone marrow cells was five-fold greater than that of the other cells.
      The in vitro metabolic and binding studies with bone marrow cells, demonstrated
      that the Im in NTG metabolism and Kd for NTG binding were 94 and 142 pM,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527855
TI  - Nitric oxide synthase activity, viability and cyclic GMP levels in rat colonic
      epithelial cells: effect of endotoxin challenge.
AB  - The present study has examined whether epithelial cells could be a source of the
      inducible form of nitric oxide synthase (iNOS) in the colon of rats challenged
      with E. coli lipopolysaccharide and whether such excessive endogenous nitric
      oxide (NO) or exogenous NO released from NO donors could affect their viability.
      Epithelial cells were isolated from rat colon, and cell viability was determined
      by trypan blue exclusion. The appearance of a calcium-independent iNOS determined
      by the conversion of radiolabeled L-arginine to citrulline was observed in cells
      harvested from lipoplysaccharide (3 mg/kg for 4 hr)-treated rats, with a 10-fold
      increase in total NOS activity compared with control. This was accompanied by a 3
      fold decrease in epithelial cell viability. Levels of iNOS and of cellular injury
      were not significantly affected in rats made neutropenic by the administration of
      antineutrophil serum. Induction of NOS was also associated with an increase in
      epithelial cyclic guanylate monophosphate levels. Both iNOS activity and cell
      injury were inhibited by in vivo pretreatment with dexamethasone (1 mg/kg i.v.,
      for 4 hr) or the NOS inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg s.c.)
      in a dose that itself reduced viability. The incubation of epithelial cells with
      the NO donors, nitroprusside, S-nitroso-N-acetyl penicillamine or S-nitroso-N
      glutathione (0.1-1 mM) produced concentration-dependent cytotoxicity. These
      findings indicate that the induction of NOS in colonic epithelial cells is not
      dependent upon infiltration of neutrophils and is accompanied by a reduction in
      cellular viability, an effect mimicked in vitro by NO donors.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7527857
TI  - Ethanol inhibits glutamatergic neurotransmission in nucleus accumbens neurons by
      multiple mechanisms.
AB  - The nucleus accumbens (NAcc) likely plays a role in the rewarding effects of
      several addictive drugs such as opiates and EtOH. We showed previously that low
      EtOH concentrations reduced glutamatergic excitatory postsynaptic potentials (EP
      SPs) in NAcc neurons. Naloxone inhibited this effect. In the present study we
      have begun characterizing the receptors involved in the evoked EPSPs and examined
      the action of EtOH on these receptors by using intracellular recording (voltage-
      and current-clamp) in the rat NAcc slice. At depolarized membrane potentials, we
      found 6-cyano-7-nitroquinoxaline-2,3-di-one-resistant EPSPs that were blocked by
      the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5
      phosphonovalerate. In 6-cyano-7-nitroquinoxaline-2,3-dione (a non-NMDA glutamate
      receptor antagonist), EtOH 66 mM decreased these NMDA-EPSPs. Application of
      exogenous NMDA or non-NMDA [kainate, (R,S)-alpha-amino-3-hydroxy-5-methyli
      soxazole-4-propionic acid or quisqualate] glutamate agonists evoked reversible
      depolarizations or inward currents. The NMDA-induced currents increased with
      membrane depolarization and were blocked by DL-2-amino-5-phosphonovalerate. EtOH
      11 to 200 mM decreased the NMDA currents significantly and dose-dependently,
      without effect of naloxone. Higher EtOH concentrations (44-66 mM) also reduced
      slightly kainate-induced currents (again without a naloxone effect), but not
      (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid or quisqualate
      currents. These data suggest that NAcc core neurons express both NMDA and non
      NMDA glutamate receptors. Because low EtOH concentrations reduce the EPSPs at
      normal resting potentials, but not responses to non-NMDA glutamate agonists, EtOH
      probably acts both pre- and postsynaptically: by an opioid-dependent reduction of
      glutamate release and by postsynaptically reducing NMDA and kainate currents. By
      virtue of the likely role NAcc plays in alcoholism, these actions could represent
      major determinants in the intoxicating and reinforcing properties of EtOH.

PMID- 7527858
TI  - Colloid carcinoma of rectum in a 11 year old child.
AB  - The rarity of rectal carcinoma in children has prompted us to report this patient
      who presented with bleeding per rectum and constipation. Histopathological
      examination of biopsy revealed the growth to be a colloid carcinoma of rectum and
      it was inoperable on exploratory laparotomy. There are three factors which
      contribute to an overall poor prognosis of rectal carcinoma in children viz.
      delay in diagnosis, advanced stage of disease and poorly differentiated
      histology.

PMID- 7527859
TI  - Efficacy of intraperitoneal sodium carboxymethylcellulose in preventing
      postoperative adhesion formation.
AB  - Various regimens to reduce postoperative intraperitoneal adhesion formation have
      been tested; however, none has been consistently successful. The purpose of this
      study was to compare the efficacy of three compounds instilled into the
      peritoneal cavity--32% dextran 70, 0.9% normal saline and sodium
      carboxymethylcellulose--to no therapy on their ability to prevent postoperative
      adhesion formation in the New Zealand white rabbit. Bilateral posterior uterine
      horn incisions and cecal and transverse colon abrasions were performed during a
      two-phased study on each of 25 rabbits that were randomly assigned in a blind
      fashion into one of four study groups. Two weeks postoperatively, each rabbit
      underwent an autopsy to assess the magnitude of intraperitoneal adhesion
      formation. Adhesion scores were determined by counting the number of adhesions
      and assigning one or two points for each thin, filmy or dense, broad adhesion. As
      compared to no therapy, all three substances tested significantly reduced
      adhesion formation. Although 32% dextran 70 and 0.9% normal saline showed similar
      results, the degree of adhesion formation was reduced most significantly with
      sodium carboxymethylcellulose (P < .002) Sodium carboxymethylcellulose is
      effective in preventing postoperative adhesion formation in the New Zealand white
      rabbit.

PMID- 7527860
TI  - Acute effects of intravascular absorption of 32% dextran 70 on blood coagulation,
      electrolytes and arterial blood gas.
AB  - Thirty-two percent dextran 70 is used to help visualize the uterine cavity during
      hysteroscopy and is also used intraperitoneally to prevent adhesions. We measured
      serum electrolytes, serum osmolarity, hematocrit, arterial blood gas and
      coagulation profile in 11 patients receiving dextran 70 while undergoing
      hysteroscopy. Dextran 70 had no significant effect on prothrombin time, partial
      thromboplastin time, thrombin time, fibrinogen level or serum osmolarity. There
      was a significant decrease in hematocrit, serum sodium and oxygen tension of
      arterial blood (PaO2). The decrease in sodium and hematocrit suggested
      hemodilution. This study demonstrated that 32% dextran 70 had a minimal effect on
      the majority of laboratory parameters measured.

PMID- 7527861
TI  - Importance of parallel vectors and "hydrophobic collapse" of the aligned aromatic
      rings: discovery of a potent substance P antagonist.

PMID- 7527862
TI  - DNA-directed alkylating agents. 6. Synthesis and antitumor activity of DNA minor
      groove-targeted aniline mustard analogues of pibenzimol (Hoechst 33258)
AB  - A series of nitrogen mustard analogues of the DNA minor groove binding
      fluorophore pibenzimol (Hoechst 33258) have been synthesized and evaluated for
      antitumor activity. Conventional construction of the bisbenzimidazole ring system
      from the piperazinyl terminus, via two consecutive Pinner-type reactions, gave
      low yields of products contaminated with the 2-methyl analogue which proved
      difficult to separate. An alternative synthesis was developed, involving
      construction of the bisbenzimidazole from the mustard terminus, via Cu(2+)
      promoted oxidative coupling of the mustard aldehydes with 3,4-diaminobenzonitrile
      to form the monobenzimidazoles, followed by a Pinner-type reaction and
      condensation with 4-(1-methyl-4-piperazinyl)-o-phenylenediamine. This process
      gives higher yields and pure products. The mustard analogues showed high
      hypersensitivity factors (IC50AA8/IC50 UV4), typical of DNA alkylating agents.
      There was a large increase in cytotoxicity (85-fold) across the homologous series
      which cannot be explained entirely by changes in mustard reactivity and may be
      related to altering orientation of the mustard with respect to the DNA resulting
      in different patterns of alkylation. Pibenzimol itself (which has been evaluated
      clinically as an anticancer drug) was inactive against P388 in vivo using a
      single-dose protocol, but the short-chain mustard homologues were highly
      effective, eliciting a proportion of long-term survivors.

PMID- 7527863
TI  - On withholding nutrition and hydration in the terminally ill: has palliative
      medicine gone too far?
AB  - This paper explores ethical issues relating to the management of patients who are
      terminally ill and unable to maintain their own nutrition and hydration. A policy
      of sedation without hydration or nutrition is used in palliative medicine under
      certain circumstances. The author argues that this policy is dangerous,
      medically, ethically and legally, and can be disturbing for relatives. The role
      of the family in management is discussed. This issue requires wide debate by the
      public and the profession.

PMID- 7527865
TI  - [T cell development and selection in extrathymic environments].
AB  - Thymocytes express randomly diversified TCRs by TCR gene rearrangement and those
      reactive to self antigens are negatively selected while those capable of
      recognizing antigens in the context of self MHC antigens are positively selected.
      The selection process in the thymus for forming the TCR repertoire is a basic
      rule for the formation of T cell repertoire. Recently, however, certain T cells
      have been reported to be generated extra-thymically and exhibit the restricted
      TCR repertoire. Some of these T cells are suggested to recognize self antigens in
      a non-MHC-restricted fashion. Those self antigens, such as endogenous retrovirus,
      surface activation antigens, and bacterial antigens, are induced by exogenous
      stress, transformation and invading microorganisms. T cells which recognize such
      self antigens seem to be activated and expand clonally whenever the antigens are
      expressed in the periphery. Although the biological roles of the unique T cells
      remain obscure, it is suggested that they may participate in immune surveillance
      system to monitor cell integrity and to destroy cells altered by transformation
      and infection by microorganisms.

PMID- 7527866
TI  - [Immune response against myelin basic protein and analysis of T-cell receptor in
      multiple sclerosis].
AB  - Human demyelinating disease, multiple sclerosis, is now though to be caused by
      autoreactive T cells against several antigens in central nervous system. In
      experimental allergic encephalomyelitis, animal model of the disease, successful
      treatment is reported using a monoclonal antibody to T-cell receptor (TCR) of
      encephalitogenic T cells. Analoging this model, researchers are now trying to
      intervene T cells suspected to elicit the disease. For this purpose, myelin basic
      protein, one of the candidate CNS antigens, reactive T cells and usage of TCR in
      those cells are extensively examined. Although no convincing result was obtained
      so far because of complexity of the disease and a genetic background of human
      beings, T cell intervention may be beneficial to some patients with this disease.

PMID- 7527864
TI  - Augmentation of alveolar macrophage phagocytic activity by granulocyte colony
      stimulating factor and interleukin-1: influence of splenectomy.
AB  - The use of cytokines and other naturally occurring substances as
      biopharmaceuticals for modulating the host response to trauma and infection
      offers new therapeutic possibilities. Cytokine pretreatment protects animals in a
      variety of experimental models, including splenectomized mice following
      pneumococcal aerosol challenge. Since splenectomy appears to affect alveolar
      macrophage function, we postulated that pretreatment with interleukin 1 (IL-1)
      and granulocyte colony stimulating factor (G-CSF) improved survival in mice
      following aerosol challenge of live pneumococci by activating alveolar
      macrophages. Alveolar macrophage bactericidal and phagocytic function was
      slightly, but consistently, depressed following splenectomy. Interleukin-1 and G
      CSF pretreatment had pronounced effects on macrophage phagocytic and bactericidal
      activity, and these effects were quite different depending upon whether the mice
      were eusplenic or asplenic. Splenectomy augmented the effects of IL-1 on alveolar
      macrophage bactericidal function compared with eusplenic mice (p < 0.001), while
      more pronounced effects on macrophage function following G-CSF treatment were
      seen in mice with intact spleens (p < 0.001). The use of cytokines and other
      substances to modify the host response to infection has great potential.
      Individuals with deficits such as splenectomy will have a different net response
      to therapy. It is important that we be able to predict these responses accurately
      in most patients in order to use these substances more effectively.

PMID- 7527867
TI  - [T cell immunity to proteolipid protein (PLP) in multiple sclerosis (MS):
      identification of DR2-associated PLP determinants and conserved TCR CDR3 motifs].
AB  - Multiple sclerosis is assumed to be an autoimmune disease mediated by T cells
      specific for myelin protein, such as, myelin basic protein (MBP) and PLP. Several
      groups reported that PLP-specific T cells are activated in the cerebrospinal
      fluid and, to a lesser extent, in the peripheral blood of the patients. We
      identified seven T cell epitopes within PLP residue 85-159. The T cell responses
      to these epitopes were higher in MS than in healthy subjects. PLP 95-116 and 105
      124 specific T cells were more frequently established from DR2 MS than from non
      DR2 MS, indicating that the DR2 restricted T cells recognizing these determinants
      are involved in the pathogenesis of MS. It is found PLP-specific T cells
      preferentially use V beta 5 and V beta 2 families though the usage is not
      exclusive. TCR beta chain complementary determining region 3 (CDR3) amino acid
      motifs of some PLP-specific T cells were homologous to those of MS lesion T
      cells, so it is likely that PLP-specific T cells infiltrate MS lesions. To our
      surprise, the CDR3 motifs of PLP-specific clones resemble those of MBP-specific
      clones. According to these facts, some antigen-independent pressure might give a
      common structure to T cells involved in MS.

PMID- 7527868
TI  - [Selective gene therapy of malignant gliomas using brain-specific promoters: its
      efficacy and basic investigations].
AB  - Retroviral vector is often used for gene therapy of malignant tumors. The main
      characteristic of this vector is that it integrates only into the genes of
      dividing and proliferating cells. Glioma cells proliferate actively, while
      surrounding normal brain cells rarely divide. Thus, we can expect the recombinant
      retrovirus modified to express cytotoxic genes to kill glioma cells selectively.
      However, this characteristic of specific toxicity to the dividing cells is also
      observed in many chemotherapeutic agents, and it is well known that they cause
      severe side effects, such as bone marrow suppression or diarrhea caused by
      simultaneous toxicity of the drugs to proliferating bone marrow cells or
      intestinal epithelial cells, respectively. We have cloned many genes which are
      specifically expressed in brain, and identified their promoter regions conferring
      tissue-specific expression. If we use the brain-specific promoters to regulate
      the expression of the toxic genes, these genes may not be expressed in the
      myeloid cells or intestinal epithelial cells, even if they were infected with the
      retrovirus. Therefore, we searched for brain-specific promoters which are also
      active in glioma cells to kill glioma cells specifically. Then, MBP promoter
      showed the strongest promoter activity in mouse glioma cells. These mouse glioma
      cells transduced with retrovirus containing the MBP promoter directing the herpes
      simplex virus type 1 thymidine kinase (HTK) gene were extremely sensitive to
      ganciclovir, even when transduced with the MBP promoter-HTK gene-containing
      retrovirus. And we could get complete remission in the mouse brain tumor models,
      which were transfected HTK genes in more than 25% glioma cells, with
      ganciclovir.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527869
TI  - [Clinical significance of determination of anti-HCV antibodies].
AB  - This study was conducted to evaluate the clinical significance of assays of
      hepatitis C virus (HCV) antibodies to manage the liver diseases due to HCV. To
      detect HCV infection accurately, the second-generation anti-HCV assays such as
      EIA, PHA and TND-2 were more useful than other assays such as anti-C100-3
      antibody, anti-GOR antibody, and anti-JCC-2 antibody, because the second
      generation anti-HCV assays showed positive rates in over 90% of the cases with
      positive HCV-RNA. Although in some patients the determination of anti-GOR, anti
      JCC-2, IgM anti-HCV and their titrations revealed the severity of liver disease
      and were useful to predict the effects of interferon therapy, measurements of
      these antibodies were not considered so useful as clinical parameters for
      management of patients with liver disease due to HCV. However, the fact that the
      changes of serum titer of anti-JCC-2 correlated well to the changes of serum
      transaminase levels in a few patients with IFN suggests that the clinical
      significance of anti-HCV core antibodies should be further discussed.

PMID- 7527870
TI  - [Predicting factors for the response to interferon therapy against hepatitis C
      virus infection: HCV genotyping].
AB  - The predictive factors in the efficacy of interferon therapy were analyzed on the
      patients with chronic hepatitis C by multivariate analysis, and HCV genotype and
      histological diagnosis were found useful for predicting the response to
      interferon therapy. Of the patients, 57% were found to be infected with HCV II,
      27% were with HCV III, and 3% were with HCV IV. HCV I was not found in our
      patients. The complete response rate of the patients with HCV II (21%) was
      significantly lower than that of HCV III (63%). The concentration of HCV RNA was
      significantly larger in the patients with HCV II than in those with HCV III. When
      the patients with equal concentrations of HCV RNA were compared, the complete
      response rate was also significantly lower in the patients with HCV II than in
      those with HCV III. On histological diagnosis, the patients with mild disease
      were significantly more responsive than those with severe disease. The complete
      response rate of the patients with HCV II who have severe histological lesions
      (severe CAH) was 7%. On the other hand, the complete response rate of the
      patients with HCV III and a histological diagnosis of mild disease (CPH or mild
      CAH) was 80%. Our findings suggest that the outcome of interferon therapy can be
      predicted to some degree from the pretreatment data.

PMID- 7527871
TI  - [Early detection of hepatocellular carcinoma with lectin reactive alpha
      fetoprotein].
AB  - Lens culimaris agglutinin A-reactive alpha-fetoprotein (AFP L3) and
      erythroagglutinating phytohemagglutin-reactive alpha-fetoprotein (AFP P4 + P5)
      were determined by a sensitive method using lectin-affinity electrophoresis
      coupled with antibody-affinity blotting, and the usefulness of this method for
      early detection of hepatocellular carcinoma (HCC) was examined. For 72 operated
      cases of the HCC group including 28 cases of small liver cancer, the AFP value
      was 124 +/- 198ng/ml (Mean +/- SD); the lectin fraction values for L3 and P4 + P5
      were 12.2 +/- 17.9 and 17.9 +/- 17.9%, respectively, which were significantly
      higher compared with the chronic hepatitis (CH).cirrhosis (LC) group and showed
      an increasing tendency with an increase in tumor diameter. The cut-off values for
      distinguishing HCC from CH.LC, determined with the receiver-operating
      characteristic (ROC) plots, were 10.0 and 15.0% for the L3 and P4 + P5 fractions,
      respectively, and the positive rates in the patient with HCC were 33.3 and 48.6%
      for AFP L3 and AFP P4 + P5, respectively, and 59.7% with a combination assay. For
      small liver cancer, the positive rate was 17.9% with protein induced by vitamin K
      absence-II (PIVKA-II) and 46.4% with combination assay of AFP L3 and AFP P4 + P5.
      Also, for HCC below AFP 50ng/ml, a positive rate of 45.0% was obtained. In the
      CH.LC group, all cases were negative for AFP L3 and 2 of 44 cases (4.5%) were
      false-positive for AFP P4 + P5.

PMID- 7527872
TI  - Renal vasoconstriction during inhibition of NO synthase: effects of dietary salt.
AB  - Since dietary salt loading enhances nitric oxide (NO) generation in the kidney,
      we investigated the hypothesis that changes in salt intake have specific effects
      on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We
      contrasted changes in renal and hindquarter vascular resistances (RVR and HQVR)
      in anesthetized rats during intravenous infusions of graded doses of the NO
      synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Groups (N = 8 to
      10) of rats were maintained on a high salt (HS) or low salt (LS) diet for two
      weeks. Compared to those on LS, rats on HS had a greater increase in mean
      arterial pressure (delta MAP; +32 +/- 4 vs. +22 +/- 3%; P = 0.05) and RVR (+160
      +/- 17 vs. +83 +/- 10%; P < 0.005) and a greater fall in renal blood flow (delta
      RBF; -47 +/- 3 vs. -32 +/- 4%; P < 0.01); changes in HQVR were similar in the two
      groups. The enhanced RVR response to L-NAME in HS rats could not be ascribed to
      the higher renal perfusion pressure (RPP) since it persisted in rats whose RPP
      was controlled by adjustment of a suprarenal aortic clamp. Changes in RVR with an
      NO donor (SIN-1) were similar in HS and LS rats. L-NAME reduced plasma renin
      activity in both HS and LS rats. After inhibition of ACE with captopril, or of
      angiotensin II type I (AT1) receptor with losartan, the increase in RVR with L
      NAME remained greater in HS than LS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527873
TI  - Evidence that the inhibition of Na+/K(+)-ATPase activity by FK506 involves
      calcineurin.
AB  - We reported that cyclosporin A (CsA) inhibits Na+/K(+)-ATPase activity in
      specific segments of the rat nephron. In this study, we tested the hypothesis
      that cyclosporin A reduces Na+/K(+)-ATPase activity through inhibition of
      calcineurin. In T cells, cyclosporin A and FK506 bind to immunophilins and
      inhibit the phosphatase activity of calcineurin; Rapamycin and SDZ 220-384 also
      bind to immunophilins but do not change calcineurin activity. Na+/K(+)-ATPase
      activity was measured in microdissected rat proximal tubule (S2 subsegment),
      medullary thick ascending limb (mTAL), and cortical collecting duct (CCD). First
      we found that two inhibitors of calcineurin, pentafluorophenol (PFP, 100 mM) and
      peptide 412 (1 mM), significantly reduced Na+/K(+)-ATPase activity in the CCD by
      78% and 70%, respectively. In CCDs, FK506 inhibited Na+/K(+)-ATPase activity by
      61 to 85% at concentrations of 1.5 to 6 ng/ml, but not at 0.5 ng/ml. FK506 (6
      ng/ml) inhibited Na+/K(+)-ATPase activity in mTALs by 56% but did not inhibit it
      in S2s or glomeruli. In contrast, Rapamycin (12.5 ng/ml) did not change Na+/K(+)
      ATPase activity in CCDs or mTALs, but at a concentration of 12.5 micrograms/ml
      did block the inhibitory effect of FK506 (6 ng/ml) in both segments. SDZ 220-384
      (600 ng/ml) did not change Na+/K(+)-ATPase activity in CCDs. Thus, in CCDs and
      mTALs: (1) FK506, like cyclosporin A, inhibits Na+/K(+)-ATPase activity; (2)
      Rapamycin and SDZ 220-384 do not inhibit Na+/K(+)-ATPase activity; and (3)
      Rapamycin prevents FK506-induced inhibition of Na+/K(+)-ATPase activity. These
      responses may be explained by a direct inhibition of calcineurin activity
      yielding lower Na+/K(+)-ATPase activity in CCDs and mTALs.

PMID- 7527874
TI  - Differential expression and induction of mRNAs encoding two inducible nitric
      oxide synthases in rat kidney.
AB  - We used quantitative PCR methods and renal microdissection to characterize the
      expression of inducible nitric oxide synthase (iNOS) mRNAs in rat kidney and
      cultured glomerular mesangial cells. A partial cDNA homologous to murine
      macrophage iNOS (macNOS), but distinct from rat vascular smooth muscle iNOS
      (vsmNOS), was cloned from normal rat kidney. macNOS was the principal iNOS
      isoform tonically expressed in microdissected glomeruli, proximal tubules,
      medullary thick ascending limbs (mTAL), cortical and inner medullary collecting
      ducts (IMCD), and cultured mesangial cells, whereas vsmNOS was the major isoform
      expressed in arcuate and interlobular arteries. Basal macNOS expression was
      greatest in mTALs and IMCDs. Restriction mapping of RT-PCR products indicated
      that basal expression of macNOS mRNA was comparable to that of vsmNOS in cortex,
      but greater than vsmNOS in outer and inner medulla. However, compared to
      controls, lipopolysaccharide (LPS)-treated rats exhibited a much greater
      proportion of vsmNOS mRNA and higher levels of total iNOS mRNA in each zone.
      Similarly, TNF alpha and IF-gamma preferentially induced expression of vsmNOS
      mRNA in cultured mesangial cells. We conclude that two iNOS isoforms are
      constitutively and heterogeneously expressed in the normal rat kidney, and that
      endotoxemia and cytokines differentially induce their expression.

PMID- 7527875
TI  - Inducible nitric oxide synthase mRNA and activity in glomerular mesangial cells.
AB  - Previous studies have suggested that glomerular mesangial cells produce nitric
      oxide (NO), using measurements of the NO decomposition products, NO2- and NO3-.
      We have now directly measured NO in the headspace above rat mesangial cell
      cultures, using a chemiluminescence analyzer. In addition, we examined mesangial
      cell RNA for inducible NO synthase (iNOS). We found no detectable NO in the
      headspace or iNOS mRNA in unstimulated mesangial cells. However, after four hours
      of incubation with LPS (10 micrograms/ml), iNOS mRNA was apparent and after six
      hours, significant increases in NO were detected. Both of these parameters
      continued to increase for at least 24 hours. Significant increases in NO2-/NO3-
      in the media and cGMP in the mesangial cells were also detected after 24 hours of
      incubation with LPS. The induction of iNOS mRNA by LPS was markedly inhibited by
      actinomycin D and dexamethasone, as was the accumulation of NO2-/NO3- in the
      media. Cycloheximide significantly inhibited NO2-/NO3- in the media of LPS
      treated cells, but had little effect on induction of iNOS mRNA by LPS. We
      conclude that rat mesangial cells possess an iNOS, with activity and regulation
      similar to that described in macrophages. Furthermore, we demonstrate the
      activity of this enzyme by direct measurement of NO and its decomposition
      products, NO2- and NO3-. We suggest that production of NO by glomerular mesangial
      cells could occur, even when macrophage infiltration is not present, and could,
      thereby, modulate glomerular and tubular functions within the kidney.

PMID- 7527876
TI  - Treatment with a glycosaminoglycan formulation ameliorates experimental diabetic
      nephropathy.
AB  - Previous studies have indicated that administration of glycosaminoglycans can
      prevent some of the morphological and physiological alterations which occur in
      experimental diabetic nephropathy. The aims of this study were to further
      elucidate the effect of these drugs on glomerular basement membrane permeability
      by dextran clearance studies, to test the ability of glycosaminoglycans to revert
      established diabetic nephropathy and to examine the effect of glycosaminoglycans
      on renal extracellular matrix synthesis. Five groups of Sprague-Dawley rats were
      studied for 12 months: two control groups (treated or untreated non-diabetic),
      three streptozotocin diabetic animal groups, two of which received a
      glycosaminoglycan formulation, one from the induction of diabetes and the other
      after the fifth month of diabetes. At five months the 35S-sulfate glomerular
      incorporation, albuminuria, glomerular basement membrane thickness and anionic
      charge density were determined. At 12 months albuminuria, renal collagen IV and
      perlecan mRNA levels, anionic and neutral dextran clearances, glomerular basement
      membrane morphometry, and mesangial cell proliferation were evaluated. We
      demonstrate that long-term administration of glycosaminoglycans prevents renal
      morphological and functional alterations in diabetic rats and appears to revert
      established diabetic renal lesions. Glycosaminoglycan administration modified
      renal matrix composition by the normalization of collagen gene expression and
      increasing glomerular 35S-sulfate incorporation.

PMID- 7527877
TI  - Characterization of anti-GBM antibodies involved in Goodpasture's syndrome.
AB  - Goodpasture's syndrome is a life threatening autoimmune kidney disease. The
      patients have autoantibodies to the glomerular basement membrane, which are
      specific for the C-terminal domain of type IV collagen (NC1). The major antigen
      has been localized to the alpha 3 (IV)-chain. We have investigated sera from 44
      patients with anti-NC1 antibodies. The quantity of antibodies to four different
      alpha(IV)-chains of type IV collagen was measured with direct ELISA. We used
      affinity chromatography to separate the antibodies and their specificities were
      studied with ELISA. The results show that about 1% of the patients total IgG are
      anti-NC1 antibodies and that 90% of these antibodies are specific for the alpha
      3(IV)-chain. Antibodies to the other alpha(IV)-chains were found in 80% of the
      patients. Furthermore, affinity purified anti-alpha 3(IV) antibodies from one
      patient were inhibited by antibodies from the other patients, from 4 to 72%. The
      antibodies, from 39 of the patients, were inhibited by a monoclonal antibody
      against the alpha 3(IV)-chain. The results indicate that patients with
      Goodpasture's syndrome can have antibodies to most of the alpha(IV)-chains, while
      the majority of anti-NC1 antibodies are restricted to the alpha 3(IV)-chain.
      Moreover the number of epitopes seems to be limited and the majority of the
      antibodies from most patients are against one single epitope on the alpha 3(IV)
      chain.

PMID- 7527879
TI  - [Non-arteritic anterior ischemic optic neuropathy: long-term results after
      hemodilution therapy].
AB  - BACKGROUND: In patients with nonarteritic anterior ischemic optic neuropathy
      (AION) we investigated the long-term effect of hemodilution on functional
      results, recurrence rate in the affected and involvement of the second eye.
      PATIENTS AND METHODS: In a retrospective study we reviewed 24 patients ranging in
      age from 62 to 92 years (mean 77 years) with AION. The duration of follow-up was
      between 8-51 months (mean 24.8 months). All patients received iso- (Hct > 40%) or
      hypervolemic (Hct < or = 40%) hemodilution over 8-10 days with daily infusion of
      10% hydroxyethyl-starch 200/0.5. The hematocrit decreased significant (p < 0.001)
      from 43.4 +/- 3.8% to 37.8 +/- 3.5% after this 10-day hemodilution treatment.
      RESULTS: After the longterm follow-up 29.1% of the patients had an improvement of
      the central vision by two or more lines, 16.7% had a deterioration, 54.2%
      remained unchanged. The resulting visual acuity was between 0.5-1.0 in 37.5%,
      between 0.4-0.1 in 41.7% and worse than 0.1 in 20.8%. Neither visual fields nor
      the VECP were significant changed by hemodilution. After the mean follow-up
      period of 24.8 months no recurrence occurred in the affected eye and the second
      eye as never involved. CONCLUSION: Hemodilution therapy has no significant
      longterm effect on visual acuity and visual fields, but it seems to have a
      beneficial influence on the recurrence rate in the affected and on the
      involvement of the second eye.

PMID- 7527878
TI  - Screening and confirmatory testing of cadaver organ donors for hepatitis C virus
      infection: a U.S. National Collaborative Study.
AB  - Hepatitis C virus (HCV) can be transmitted by organ transplantation. Cadaver
      organ donors are screened for HCV infection by testing for antibodies to HCV
      (anti-HCV). The prevalence of HCV infection and performance of anti-HCV tests in
      detecting HCV infection in organ donors are unknown. Sera from 3078 cadaver organ
      donors were tested for anti-HCV by a first generation enzyme-linked immunosorbent
      assay (ELISA1). Sera from all 137 ELISA1 positive donors and a random sample of
      92 ELISA1 negative donors were tested for anti-HCV by a second generation ELISA
      (ELISA2) and for HCV RNA by the polymerase chain reaction. Organ bank records
      were reviewed for risk factors associated with HCV infection. Follow-up was
      available on 70 recipients of organs from 42 ELISA2 positive donors. The
      prevalence of HCV RNA, extrapolated to all 3078 donors, was 2.4%. Liver disease,
      anti-HCV and HCV RNA were detected more frequently among recipients of organs
      from ELISA2 positive donors with HCV RNA than from ELISA2 positive donors without
      HCV RNA. Among donors, the sensitivity and negative predictive value of the
      ELISA2 for HCV RNA were 100%. However, despite a specificity of 98.1%, the
      positive predictive value was only 55.1%. Clinical and laboratory characteristics
      did not distinguish ELISA2 positive donors with and without HCV RNA. The presence
      of serum HCV RNA in organ donors predicts the risk of transmission of HCV
      infection. Discarding organs from ELISA2 positive donors would eliminate
      transmission, but organs from 1.88 percent of donors would be wasted.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7527881
TI  - The on-off mechanisms of the nicotinic acetylcholine receptor ion channel are
      performed by thermodynamic forces.
AB  - The active sites of nicotinic acetylcholine receptors are comparatively strong
      hydrophobic areas. When nicotinic acetylcholine receptor alpha-subunits bind with
      acetylcholines, the polar groups of nicotinic acetylcholine receptors and
      acetylcholines become more hydrophobic owing to repulsion of the bound water
      molecules, and the charged groups of nicotinic acetylcholine receptors and
      acetylcholines are neutralized. Thus, the large hydrophobic areas form at and
      around the binding sites of nicotinic acetylcholine receptors and acetylcholines.
      These exposed hydrophobic areas are unstable thermodynamically (oil in water),
      and thus sink toward the neighboring hydrophobic transmembrane segment (M2). The
      sinking of the acetylcholine-binding sites with the M2, which contains an ion
      channel, causes the negative residues of the top of the M2 to descend to the
      hydrophilic level of the immobile M2 of the other nicotinic acetylcholine
      receptor subunits. This pathway, which consists of hydrophilic part of the sunken
      alpha-subunits and the hydrophilic part of the immobile M2 of other subunits,
      allows for the easy passage of cations across the cellular membrane. The
      movements of the alpha-subunits sinking to the transmembrane area cause the
      release of acetylcholines from binding sites. The hydrophilic groups of
      acetylcholines (quaternary ammonium ion, etc) and nicotinic acetylcholine
      receptors (ionic groups of M2, etc) are unstable in hydrophobic conditions (water
      in oil), resulting in the binding site and the hydrophilic residues of M2
      returning to the positions in the resting state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527880
TI  - Hypertonic saline/dextran for cardiopulmonary bypass reduces gut tissue water but
      does not improve mucosal perfusion.
AB  - Gut mucosal ischemia has been associated with cardiopulmonary bypass (CPB) and
      may contribute to postoperative systemic inflammatory response and multiorgan
      dysfunction. Hypertonic saline/dextran (HSD) has been previously shown to
      selectively increase mucosal blood flow in circulatory shock. To determine
      whether adding HSD to the prime solution for CPB improves gut mucosal blood flow
      and oxygenation, we performed normothermic, non-cross-clamped CPB in pigs with 1
      ml/kg of HSD (25% NaCl/24% dextran 70) (HSD group, n = 9) or lactated Ringer's
      solution (LRS group, n = 9) as control added to a standard prime. Animals were
      instrumented with ultrasonic flow probes on the superior mesenteric artery (SMA),
      laser Doppler mucosal flow probes in the ileum, and indwelling portal vein
      catheters and tonometers for mucosal hydrogen ion measurements and pH
      calculations in the stomach, ileum, and rectum. The total infused volume and net
      fluid balance was significantly lower in the HSD than in the LRS group (649 +/-
      171 ml vs 2075 +/- 385 ml and 502 +/- 182 ml vs 1891 +/- 363 ml, respectively, P
      < 0.01). SMA flow in the LRS group increased to 110-123% of baseline during CPB
      and was significantly higher than that in the HSD group which remained unchanged.
      Ileal mucosal blood flow decreased significantly to 70-50% of baseline in both
      groups with no difference between groups. Gut oxygen (O2) delivery decreased
      during CPB in both groups, but O2 consumption remained unchanged. Gastric, ileal,
      and rectal mucosal pH decreased progressively, and portal venous blood pH also
      decreased in both groups, but there was no significant difference between
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527882
TI  - Detection of aneuploid cells in acute lymphoblastic leukemia with flow cytometry
      before and after therapy.
AB  - We have evaluated the proliferative activity and DNA content of immunophenotyped
      hematopoietic cells applying flow cytometry. After indirect immunofluorescence
      the cell membrane was permeabilized for propidium iodide staining of DNA.
      Compared with single parameter detection of DNA content this method has more
      certainty in the determination of aneuploidies in lymphatic leukemia cells.
      Immunophenotyped residual normal hematopoietic cells were used as an internal
      standard. If this method was tested for evaluation of therapeutic effects after
      chemotherapy greater sensitivity in detection of minimal residual disease was
      observed than when using microscopic evaluation or single parameter DNA analysis
      in cases of aneuploid lymphoblastic leukemias.

PMID- 7527883
TI  - Establishment of a retrodifferentiated cell line from a single differentiated rat
      myelomonocytic leukemia cell: possible roles of retrodifferentiation in relapses
      of leukemia after differentiation-inducing therapy.
AB  - In order to demonstrate possible roles of retrodifferentiation in relapses after
      differentiation therapies, we have established a retrodifferentiated cell line
      (RD-1) from a single rat myelomonocytic leukemia cell which differentiated into a
      macrophage-like cell by treatment with lipopolysaccharide (LPS). The established
      RD-1 cells showed microscopic features slightly maturer than their parent cells.
      The RD-1 cells had the ability to differentiate into macrophage-like cells by
      treatment with fewer doses of LPS than those for parent cells. All rats
      inoculated with the parent cells (more than 10(2)/rat) died within 50 days. Rats
      inoculated with 10(4) RD-1 cells survived for more than 120 days, whereas two out
      of four rats inoculated with 10(5) cells and all the rats inoculated with 5 x
      10(5) cells died of leukemia. These results suggest that RD-1 cells are
      retrodifferentiated cells from a single rat myelomonocytic leukemia cell which
      differentiated into a macrophage-like cell; they have similar phenotypes and
      lower tumorigenicity than the parent cells and they also suggest that the
      appearance of retrodifferentiated leukemia cells may be responsible for relapse
      after differentiation therapy for leukemia in some cases.

PMID- 7527884
TI  - [Treatment with interferon in chronic hepatitis. General Subdirectorate of
      Services and Evaluation of Health Technologies, General Directorate of Assurance
      and Health Planning, Ministry of Health and Consumption].

PMID- 7527885
TI  - Functional autoimmune epitope on alpha 1-adrenergic receptors in patients with
      malignant hypertension.
AB  - Because of the growing evidence that hypertensive disease is accompanied by
      immunological dysfunction, we have investigated autoimmunity in patients with
      malignant hypertension. Peptides corresponding to the sequence of the second
      extracellular loops of the human alpha 1-adrenergic receptor and the M2
      muscarinic receptor were used as antigens in an ELISA. Serum from 4 (12%) of 33
      healthy controls, 3 (20%) of 15 patients with malignant essential hypertension,
      and 7 (64%) of 11 with secondary hypertension showed positive responses in the
      ELISA for the alpha 1-adrenergic receptor peptide. Positive responses were
      significantly more common among the patients with secondary hypertension than in
      the other two groups (p < 0.01). By contrast, no autoantibodies against the M2
      muscarinic receptor peptide were detected in either hypertensive group.
      Autoantibodies against the alpha 1-adrenergic receptor, affinity-purified from
      patients with positive responses, specifically recognised bands with molecular
      masses of 68, 40, and 37 kDa on immunoblotted membrane proteins of rat
      ventricles. The patients' autoantibodies caused a decrease in tritiated prazosin
      binding sites and an increase in heart beating frequency of neonatal cultured rat
      cardiomyocytes; antibodies purified from the controls had no effect. Circulating
      autoantibodies against the alpha 1-adrenergic receptor are present in a subgroup
      of patients with malignant hypertension. These autoantibodies have
      pharmacological activity in vitro, which suggests that they may be involved in
      the pathogenesis of malignant hypertension.

PMID- 7527886
TI  - Risperidone-induced neuroleptic malignant syndrome in young patient.

PMID- 7527887
TI  - Phthalocyanine photodynamic therapy: new strategy for closure of choroidal
      neovascularization.
AB  - Chloro-aluminum sulfonated phthalocyanine (CASPc) is a photo-chemically active
      dye employed in photodynamic therapy (PDT). CASPc is a potent generator of
      singlet oxygen when irradiated with 675 nm light and is also capable of
      fluorescence, allowing visualization of the dye in tissues. We devised an
      angiography system using CASPc fluorescence to determine its localization in
      experimental choroidal neovascularization in monkeys and then investigated the
      ability of CASPc to produce photochemical closure of neovascularization upon
      irradiation with 675nm laser light. Fluorescent imaging indicated that CASPc
      localized angiographically in areas of neovascularization for at least 24 hours.
      Irradiation with 675 nm laser light 5-30 minutes after CASPc injection produced
      complete closure of choroidal neovascularization with minimal damage to overlying
      retina. We conclude that CASPc localizes in neovascular choroidal vessels and
      that CASPc photodynamic therapy can produce closure of these choroidal vessels.

PMID- 7527888
TI  - Selective MAO-A and B inhibitors, radical scavengers and nitric oxide synthase
      inhibitors in Parkinson's disease.
AB  - In the absence of identification of either an endogenously or an exogenously
      derived dopaminergic neurotoxin, the most valid hypothesis currently envisaged
      for etiopathology of Parkinson's disease (PD) is selective oxidative stress (OS)
      in substantia nigra (SN). Although OS is not proven, a significant body of
      evidence from studies on animal and Parkinsonian brain neurochemistry supports
      it. This hypothesis is based on excessive formation of reactive oxygen species
      (O2 and OH.) and demise of systems involved with scavenging or preventing the
      formation of such radicals from H2O2, generated as a consequence of dopamine
      oxidation (autoxidation and deamination). Since MAO (monoamine oxidase A and B
      are the major H2O2 generating enzymes in the SN much attention has been paid to
      their selective inhibitors as symptomatic and neuroprotective agents in PD.
      Attention should also be given to radical scavengers (e.g. iron chelators, lipid
      peroxidative inhibitors and Vitamin E derivatives) as therapeutic neuroprotective
      agents in PD. This is considered valid since a significant elevation of iron is
      known to occur selectively in SN zone compacta and within the remaining melanized
      dopamine neurons of Parkinsonian brains. Although all the mechanism of iron
      induced oxygen free radical formation is not fully known there is no doubt that
      it participates with H2O2 (Fenton chemistry) to generate cytotoxic hydroxyl
      radical (OH.) and induce tissue OS and neurodegeneration in 6-hydroxydopamine
      model of PD. The dramatic proliferation of reactive amoeboid macrophages and
      microglia seen in SN of PD brains together with OS is highly compatible with an
      inflammatory process, similar to what has been observed in Alzheimer's disease
      and multiple sclerosis brains. This has led us to examine the ability of reactive
      macrophages to produce oxygen free radicals in response to nitric oxide (NO)
      production. The latter radical has been implicated in the excitotoxicity of
      glutaminergic neurons innervating the striatum and SN. Indeed we have now
      observed that in reactive macrophages NO acts as a signal transducer of O2
      production which can synergize with dopamine oxidation.

PMID- 7527889
TI  - Histological evolution of chronic hepatitis C. Factors related to progression.
AB  - We have evaluated the histological progression of liver disease in 29 untreated
      patients with chronic hepatitis C. All patients were positive to antibodies to
      hepatitis C virus by ELISA2 and RIBA2. Two liver biopsies were carried out for
      each patient, with an interval ranging between 12 and 126 months (mean 50.2 +/-
      30.7). In all cases the usual histological classification was applied and the
      histological activity index scoring system according to Knodell et al. was
      determined. Fifteen cases worsened (51.7%), 12 cases showed no histological
      changes (41.4%) and two patients improved (6.9%). Cirrhosis was found in five
      patients (18.5%) in the second liver biopsy. Epidemiological, clinical,
      biochemical and histological progression and the group with impairment in liver
      histology. Factors related to histological worsening were: more advanced age (p =
      0.002), high levels of aspartate aminotransferase (p = 0.04), high global
      histological activity index (p = 0.03) and piecemeal necrosis and bridging
      necrosis scores (p = 0.02) at first biopsy. The histological activity index can
      be applied to assess the natural history of chronic viral hepatitis, and is a
      good tool to evaluate the prognosis. Thus chronic hepatitis C virus infection is
      a histologically progressive disease in at least half the cases.

PMID- 7527890
TI  - Quantitative radial imaging of porous particles beds with varying water contents.
AB  - Radial imaging protocols suitable for monitoring water transport in biopolymer
      and food materials during processes such as drying and rehydration are developed
      and tested on a well-characterized model sample. This model consisted of a
      randomly packed bed of Sephadex beads with varying water content. The results are
      interpreted with theoretical models for the dependence of the initial water
      magnetization, transverse relaxation, and diffusive attenuation on water content
      for two slice-selective radial imaging pulse sequences. It is shown that volume
      shrinkage and changes in packing density complicate the dependence of the initial
      magnetization on water content, so that the transverse relaxation rate provides
      the most reliable monitor of water content. Radial imaging is shown to offer many
      advantages over conventional two-dimensional imaging whenever the sample can be
      made with cylindrical symmetry.

PMID- 7527891
TI  - tRNA-directed transcription antitermination.
AB  - At least 18 aminoacyl-tRNA synthetase and amino acid biosynthesis genes in
      several Gram-positive genera appear to be regulated by a common transcription
      antitermination mechanism. Each gene is induced by limitation for the appropriate
      amino acid, and not by general amino acid limitation. The mRNA leader regions of
      these genes exhibit extensive structural conservation. Characterization of the
      Bacillus subtilis tyrS gene revealed that uncharged tyrosyl-tRNA promotes
      readthrough of a leader-region terminator; a conformational switch in the leader
      mRNA between a terminator structure and an antiterminator structure is postulated
      to mediate antitermination. Two sites of interaction between the tRNA and the
      leader have been identified by genetic analysis: the tRNA anticodon interacts
      with a single codon displayed at a precise position in the leader-region
      structure, and the acceptor end of the tRNA interacts with a side-bulge on the
      antiterminator.

PMID- 7527892
TI  - The rfb locus from Pseudomonas aeruginosa strain PA103 promotes the expression of
      O antigen by both LPS-rough and LPS-smooth isolates from cystic fibrosis
      patients.
AB  - Strains of Pseudomonas aeruginosa initially isolated from patients with cystic
      fibrosis (CF) often express a smooth lipopolysaccharide (LPS) containing many
      long O side-chain antigens, but once a chronic infection is established, strains
      recovered from these patients express little or no LPS O antigen. The genetic
      basis for this loss of O antigen expression by P. aeruginosa CF isolates is
      unknown. We report here that 20 CF isolates of P. aeruginosa, 13 of which are LPS
      rough, were each capable of expressing serogroup O11 antigen when provided with
      the rfb locus from P. aeruginosa serogroup O11 strain PA103 on the recombinant
      plasmid pLPS2. Eight of the thirteen LPS-rough isolates co-expressed another,
      presumably endogenous, O antigen when they contained pLPS2. Different subcloned
      regions of pLPS2 complemented distinct strains to restore endogenous O antigen
      expression. These data suggest that the loss of O antigen expression by P.
      aeruginosa CF isolates results from alterations specific to the rfb region, and
      is not due to mutations involving other loci or ancillary LPS genes.

PMID- 7527894
TI  - Domain structure and conserved epitopes of Sfb protein, the fibronectin-binding
      adhesin of Streptococcus pyogenes.
AB  - Streptococcus pyogenes expresses a fibronectin-binding surface protein (Sfb
      protein) which mediates adherence to human epithelial cells. The nucleotide
      sequence of the sfb gene was determined and the primary sequence of the Sfb
      protein was analysed. The protein consists of 638 amino acids and comprises five
      structurally distinct domains. The protein starts with an N-terminal signal
      peptide followed by an aromatic domain. The central part of the protein is formed
      by four proline-rich repeats which are flanked by non-repetitive spacer
      sequences. A second repeat region, consisting of four repeats that are distinct
      from the proline repeats and have been shown to form the fibronectin-binding
      domain, is located in the C-terminal part of the protein. The protein ends with a
      typical cell wall and membrane anchor region. Comparative sequence analysis of
      the N-terminal aromatic domain revealed similarities with carbohydrate-binding
      sites of other proteins. The proline repeat region of the Sfb protein shares
      characteristic features with proline-rich repeats of functionally distinct
      surface proteins from pathogenic Gram-positive cocci. Immunoelectron microscopy
      revealed an even distribution of the fibronectin-binding domain of Sfb protein on
      the surface of streptococcal cells. Analyses of 38 sfb genes originating from
      different S. pyogenes isolates revealed primary sequence variability in regions
      coding for the N-termini of mature Sfb proteins, whereas sequences coding for the
      central and C-terminal repeats were highly conserved. The repeat sequences are
      postulated to act as target sites for intragenic recombination events that result
      in variable numbers of repeats within the different sfb genes. A model of the Sfb
      protein is presented.

PMID- 7527895
TI  - Vitamin B12 repression of the cob operon in Salmonella typhimurium: translational
      control of the cbiA gene.
AB  - Expression of the cob operon is repressed by B12 via a post-transcriptional
      control mechanism which requires sequence elements within the leader region of
      the mRNA and the first gene of the operon, the cbiA gene. Here we show that B12
      repression of cbiA gene expression occurs at the level of translation initiation
      through sequestration of the ribosomal binding site (rbs) in an RNA hairpin.
      Analysis of mutations that destabilize or restabilize the secondary structure
      demonstrates that folding of the hairpin is essential for repression. The
      existence of the hairpin was confirmed by a secondary structure analysis of RNA
      from the wild type and three mutants. Deletions that remove the upstream part of
      the leader confer a drastic reduction in translation efficiency. This low-level
      translation is caused by the hairpin, as indicated by the finding that suppressor
      mutations that destabilize the hairpin restore efficient translation. Thus, the
      native upstream RNA functions as a translation enhancer and acts to relieve the
      hairpin's inhibitory effect on translation initiation. The inhibitory effect of
      the hairpin was confirmed by a ribosomal toeprinting analysis. We propose that
      the translational control of the cbiA gene mediates repression of the entire cob
      operon.

PMID- 7527896
TI  - Nucleoid partitioning in Escherichia coli during steady-state growth and upon
      recovery from chloramphenicol treatment.
AB  - To distinguish between a gradual or an abrupt movement of the Escherichia coli
      nucleoid during partitioning we determined the distances between nucleoid borders
      and cell poles. Measurements were performed on fixed but hydrated cells and on
      living cells growing in steady state. The distance between nucleoid outer border
      and cell pole remained constant in cells with either one or two nucleoids. Thus
      the nucleoid outer borders moved gradually during the partition process. To study
      partitioning during recovery from protein-synthesis inhibition cells were treated
      with chloramphenicol. After growth resumption, cells and nucleoids first
      elongated before partitioning occurred. Again, no indication of a rapid
      displacement of the nucleoid to one-quarter and three-quarter positions in the
      cell was observed.

PMID- 7527893
TI  - Construction and characterization of isogenic O-antigen variants of Salmonella
      typhi.
AB  - A 7.5 kb KpnI-generated fragment, from within the rfb cluster of Salmonella
      typhimurium LT2 that encodes abequose synthase (the rfbJ gene) which is necessary
      for O4 antigen synthesis, and flanking sequences, was inserted into a suicide
      vector. Using allelic exchange techniques, these rfb sequences of S. typhimurium
      were integrated into the rfb clusters of wild-type Salmonella typhi Vi-positive
      strain ISP 1820 (i.e. serotype O9,12; Vi+; H-d), S. typhi Vinegative strain H400
      (i.e. serotype O9,12; Vi-; H-d), and a double aro mutant of S. typhi ISP 1820,
      strain CVD 906, resulting in the isolation of strains H325, H404 and CVD 906-O4,
      respectively. Immunoblot analysis of lipopolysaccharide (LPS) purified from H325,
      H404 and CVD 906-O4 demonstrated that these strains express the O4 antigen (an
      abequose residue) in place of the O9 antigen (a tyvelose residue) in the LPS
      molecule. Hence, the serotype of H325 is O4,12; Vi+; H-d and the serotype of H404
      is O4,12; Vi-; H-d. DNA hybridization analysis of chromosomal DNA from H325, H404
      and CVD 906-O4 confirmed that a precise recombination event within sequences
      flanking rfbSE of S. typhi (which encodes the enzymes necessary for cytidine
      diphosphate-tyvelose synthesis) resulted in replacement of rfbSE with rfbJ (which
      encodes abequose synthase and is necessary for O4 synthesis) of S. typhimurium in
      strains H325, H404 and CVD 906-O4. The resistance of each strain to the
      bactericidal effects of guinea-pig serum (GPC) was assessed. Whereas ISP 1820,
      H325 and H404 exhibit similar resistance patterns in GPC, strain H400 is
      sensitive to the bactericidal effects of GPC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527897
TI  - Proteinaceous bacterial toxins and pathogenesis of sepsis syndrome and septic
      shock: the unknown connection.

PMID- 7527899
TI  - Prolactin-dependent activation of a tyrosine phosphorylated DNA binding factor in
      mouse mammary epithelial cells.
AB  - The mammary gland factor MGF has been described as a developmentally and
      environmentally regulated nuclear factor required for transcription of the milk
      protein gene beta-casein. In the current study the individual role of lactogenic
      hormones in the activation of MGF DNA binding and the functional relation of MGF
      to known transcription factors was investigated by electrophoretic mobility shift
      assays. DNA binding of MGF was rapidly induced by PRL in mammary epithelial
      cells. The activation was not inhibited by the protein synthesis inhibitor
      cycloheximide. The effect of PRL on MGF did not require costimulation of cells
      with the other lactogenic hormones, insulin, and glucocorticoids. Thus, MGF is
      the first example of a nuclear factor directly regulated by PRL. The MGF
      complexes formed upon initiation of lactation in the mammary gland and upon
      stimulation of mammary epithelial cells with PRL migrated at the same position in
      electrophoretic mobility shift assay, whereas the MGF complex found in mammary
      gland extracts of pregnant mice exhibited a faster mobility. In cell cultures,
      PRL-induced activation of MGF as well as up-regulation of beta-casein gene
      transcription was confined to confluent cultures of mammary epithelial cells and
      inhibited by long term incubation of cells with epidermal growth factor. MGF was
      found to be related to the nuclear factors that are activated by tyrosine
      phosphorylation when cells are stimulated with interferons or cytokines. This
      notion is supported by experimental evidence for phosphorylation of MGF on
      tyrosine and by the similar DNA recognition motifs of MGF and cytokine-activated
      factors.

PMID- 7527898
TI  - Evidence that signalling pathways by which thyrotropin-releasing hormone and
      gonadotropin-releasing hormone act are both common and distinct.
AB  - TRH and GnRH receptors are each coupled to G proteins of the Gq/11 family.
      Activation of each of these receptors by their respective ligands results in the
      stimulation of phospholipase C activity, leading to calcium mobilization and
      protein kinase C activation. Thus, the effects of TRH and GnRH may be mediated
      through the same intracellular signal transduction pathway. To compare responses
      to TRH and GnRH directly within one cell type, we have stably transfected the rat
      pituitary GH3 lactotrope cell line, which expresses the endogenous TRH receptor,
      with an expression vector containing rat GnRH receptor cDNA. Transfected cells
      specifically bound GnRH with high affinity and responded to GnRH stimulation with
      an increase in PRL mRNA levels, analogous to their response to TRH stimulation.
      Stably transfected GH3 cells, which were then transiently transfected with
      luciferase reporter constructs containing either the PRL or the glycoprotein
      hormone alpha-subunit promoter, responded to either GnRH or TRH stimulation with
      an increase in luciferase activity in a time- and dose-dependent fashion. The
      stimulatory effects of maximally effective concentrations of TRH and GnRH were
      additive on PRL, but not alpha-subunit, gene expression. These data, coupled with
      evidence of cross-desensitization of alpha-subunit, but not PRL, promoter
      activity stimulation by TRH and GnRH, suggest that there may be differences in
      the signal transduction pathways activated by TRH and GnRH receptors in the
      regulation of PRL and alpha-subunit gene expression.

PMID- 7527901
TI  - Opposite effects of the CD30 ligand are not due to CD30 mutations: results from
      cDNA cloning and sequence comparison of the CD30 antigen from different sources.
AB  - CD30L, the ligand for the activation antigen CD30, is a member of the tumor
      necrosis factor family of cytokines. Binding of CD30L to CD30, which is a member
      of the nerve growth factor/tumor necrosis factor receptor family, induces
      proliferation in peripheral blood lymphocytes and Hodgkin's derived cell lines
      with a T-cell phenotype such as HDLM-2 and L540, while cell lines derived from
      anaplastic large cell lymphomas, such as Karpas 299, undergo cell death. In order
      to investigate whether mutations of the CD30 antigen are responsible for these
      opposite effects, we cloned the open reading frame of CD30 cDNAs from the cell
      lines L540 and Karpas 299 and from peripheral blood lymphocytes by reverse
      transcriptase polymerase chain reaction. Sequencing of independent plasmid clones
      revealed that these cells have a silent transition (A-->G) at position 771 of the
      open reading frame compared to the published sequence derived from the HTLV-1+
      cell line HUT-102. As published data have shown that crosslinking of CD30 induces
      an elevation of cytosolic free calcium ([Ca2+]i) in TCR positive Jurkat cells, we
      have analysed the effect of crosslinking of CD30 on L540 and Karpas 299 cells. No
      elevations of [Ca2+]i have been observed in these cell lines after crosslinking
      of CD30 with HRS-4. We conclude (i) that the different functional effects of CD30
      in PBL, L540 and Karpas 299 are not due to differences in the primary structure
      of the receptor; and (ii) that the different responses observed upon engagement
      with CD30L for the cell lines L540 and Karpas 299 do not correlate with
      differences in mobilization of [Ca2+]i after crosslinking of CD30.

PMID- 7527900
TI  - Location of an epitope defined by an enhancing monoclonal antibody to growth
      hormone: some structural details and biological implications.
AB  - We have previously shown that a murine monoclonal antibody (MAb OA15) prepared
      against ovine GH (oGH) can enhance the somatogenic activity of bovine GH (bGH),
      as determined by increased incorporation of 35SO4(2-) into costal cartilage of
      hypopituitary Snell dwarf mice in vivo We have now established that MAb OA15 can
      also enhance the biological activity of oGH and porcine GH (pGH) in vivo. Using
      multiple pin peptide synthesis techniques a set of overlapping immobilized
      octamers representing the entire bGH sequence were synthesized and tested for
      their ability to bind MAb OA15 using an enzyme-linked immunosorbent assay. The
      pattern of binding showed that OA15 defined a functionally continuous epitope
      comprising residues 91-102. This region includes the C-terminal end of helix 2
      plus a portion of the adjacent loop linking helices 2 and 3. Polyclonal antisera
      to a synthetic peptide representing this epitope mimicked the ability of MAb OA15
      to enhance oGH, bGH, and pGH. Window size analysis showed that the heptapeptide
      94-100 (SRVFTNS) represents the minimum unit to retain full recognition of MAb
      OA15. The fact that pGH, bGH, and oGH have identical sequences in this region
      also explains the ability of OA15 to both cross-react with and enhance the
      biological activity of each of these GHs. Replacement net analysis (where each
      residue in the heptamer is substituted with each of the 19 naturally occurring L
      amino acids) demonstrated that residues R95 and T98 are critical for antibody
      binding and also indicated that the substitution of V96 with I, as found in rat
      GH, would permit the observed binding of OA15 to this hormone.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7527903
TI  - Mutagenicity of heterocyclic amines when activated by pancreas tissue.
AB  - The heterocyclic amines (HA) 2-aminodipyrido[1,2-a:3',2-d]imidazole (Glu-P-2), 2
      amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) were mutagenic in V79 cells (Chinese hamster
      lung fibroblasts) using 6-thioguanine resistance as the marker of mutagenicity.
      Pancreas duct epithelial cells (DEC) from untreated hamsters, homogenates of
      pancreas ducts from untreated hamsters and those fed a high fat diet and human
      DEC were used to activate the heterocyclic amines. When hamster cells and tissues
      were used the optimum mutation frequencies (mutants/10(6) survivors) measured
      were: Glu-P-2, 10 +/- 1; MeIQ, 28 +/- 2 (DEC), 12 +/- 2 (control, duct
      homogenate), and 21 +/- 2 (high fat diet fed, duct homogenate); PhIP, 61 +/- 5.
      When human DEC were used the optimum mutation frequencies were: MeIQ, 32 +/- 4;
      PhIP, 35 +/- 3. 3,8-Dimethylimidazo[4,5-f]quinoxaline, 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole were not
      mutagenic in this assay.

PMID- 7527904
TI  - The genotoxic potential in vitro and in vivo of the allyl benzene etheric oils
      estragole, basil oil and trans-anethole.
AB  - Estragole, trans-anethole and basil oil were tested for their ability to induce
      DNA repair in rat hepatocytes in vitro and in rat liver in an ex vivo test. There
      was a marked induction of UDS by estragole and basil oil in vitro (LOEC about 10(
      5) mol/l). The basil oil we used contained about 88.2% estragole. It is evident
      from our results that the induction of UDS with basil oil could be directly
      related to its main constituent estragole. trans-Anethole was only slightly
      effective in the in vitro UDS test. The ex vivo UDS test led to clearly elevated
      DNA repair for estragole and basil oil in rats treated orally with doses up to 2
      g/kg body weight. Estragole was not positive in a chromosomal aberration test
      with V79 cells either via direct treatment, with rat liver S9 mix or with rat
      hepatocytes as source of metabolism.

PMID- 7527906
TI  - The LacZ transgene in MutaMouse maps to chromosome 3.
AB  - Transgenic mouse models are being used with increasing frequency for mutational
      and toxicological studies. One such system. MutaMouse, contains a stably
      integrated lambda-gt10LacZ shuttle vector in the mouse genome. We describe the
      use of dual color fluorescence in situ hybridization (FISH) with Mus musculus
      whole chromosome paints and lambda DNA to map the integration site of the lambda
      transgene to band C on mouse chromosome 3.

PMID- 7527902
TI  - Sequence of the rat hypoxanthine guanine phosphoribosyl transferase (HPRT)
      transcriptional promoter region in wild-type and mutant rat liver epithelial cell
      lines.
AB  - The hypoxanthine guanine phosphoribosyltransferase (HPRT) gene is mutated by a
      variety of genotoxic agents in adult rat liver (ARL) epithelial cell lines. By
      polymerase chain reaction (PCR) amplification and DNA sequencing of rat ARL cell
      HPRT gene sequences with mouse- and rat-specific oligonucleotides, a large
      portion of the rat HPRT transcriptional promoter region was sequenced. This
      region exhibits approximately 60% homology with the corresponding mouse sequence,
      contains a similar G/C-rich region at its 3' end, and contains a similar series
      of 6-nucleotide (nt) GGGCGG repeats. To determine if this region is a target for
      mutation by different genotoxins, HPRT-deficient ARL mutants induced by 2
      acetylaminofluorene (AAF), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), or 7,12
      dimethyl-benz[a]anthracene (DMBA) were isolated and studied. A 1003-nt fragment
      of predominantly HPRT regulatory sequences was amplified by PCR using purified
      genomic DNA from 17 independent mutants and sequenced directly. None of the 17
      mutants examined exhibited any alterations in the transcriptional regulatory
      region or the 5' untranslated region of HPRT exon 1 after direct sequencing
      analysis of PCR products. In addition, none of the 2-AAF-induced mutants
      exhibited differences in in vitro transcription rates as determined by nuclear
      run-on analysis. These data suggest that regulatory sequences of the HPRT gene
      are not a primary target for mutation by the genotoxins studied.

PMID- 7527905
TI  - Comparison of the effects of DNA topoisomerase inhibitors on lymphoblasts from
      normal and Fanconi anemia donors.
AB  - DNA topoisomerases modify supercoiled DNA through concerted breaking and
      rejoining of the DNA strands and consequently play a key role in DNA biosynthesis
      and processing. It has been suggested that topoisomerases may facilitate access
      to damaged sites of excision repair enzymes due to their property to relax
      supercoiled DNA. We show here that treatment with nalidixic acid and novobiocin,
      which affects topoisomerase II activity among other targets, impairs the incision
      of 8-methoxypsoralen photoinduced DNA interstrand cross-links in normal human
      fibroblasts. Since cells derived from Fanconi anemia (FA) demonstrate
      hypersensitivity to DNA cross-linking agents associated with a reduced repair
      efficiency of cross-links, we compared the effects of different topoisomerase I
      and II inhibitors on FA and normal lymphoblasts. No differences were found in
      growth inhibition or induction of chromosome aberrations between FA and normal
      cells. The specificity of inhibitors is questionable and even if topoisomerases
      are indeed inhibited alternative pathways may be involved. However, our
      observations provisionally suggested that topoisomerases activities are normal in
      FA cells.

PMID- 7527907
TI  - Lack of DNA adduct formation in mice treated with benzene.
AB  - The potential of benzene to produce DNA adducts in B6C3F1 mice was investigated
      by the nuclease P1-enhanced 32P-postlabeling assay. The mice were daily treated
      i.p. with 500 mg/kg benzene in olive oil for 4 days, and the liver, mammary
      gland, and bone marrow were collected 24 h after the last treatment. Thin-layer
      chromatograms obtained with treated-tissue DNA specimens were qualitatively
      identical to those from corresponding olive oil-treated (control) tissue DNA.
      Quantitative evaluations revealed that there was no treatment-related increase in
      radioactivity on the chromatograms at or near the locations where the major in
      vitro adducts of phenol, hydroquinone and benzoquinone migrated. Benzene
      treatment, however, resulted in a decrease in the levels of certain endogenous
      adducts, the biological significance of which is unknown. Our results indicate
      that benzene treatment does not produce detectable levels of aromatic DNA adducts
      in mouse tissues.

PMID- 7527908
TI  - Analysis of chromosomal aberrations, sister-chromatid exchanges and micronuclei
      in peripheral lymphocytes of pharmacists before and after working with cytostatic
      drugs.
AB  - The frequencies of chromosome aberrations, SCEs and micronuclei (cytokinesis
      block method) in blood lymphocytes were compared among six nonsmoking female
      pharmacists before and after 1 year of working with cytostatic drugs. All
      possible precautions were taken to avoid exposure to cytostatics, including
      proper protective clothing and a monitored, negative-pressured working
      environment with vertical laminar flow cabinet. As referents, an age-matched
      group of six nonsmoking female hospital workers not dealing with cytostatics was
      simultaneously sampled twice with the same time interval. The pharmacists showed
      a marginally higher mean frequency of SCEs/cell (6.3; P = 0.049) after the
      working period than 1 year earlier (5.8). On the other hand, the referents, with
      no obvious exposure, had a higher mean number of cells with chromatid-type
      aberrations, gaps excluded, in the second sampling (2.0%; P = 0.048) than in the
      first one (0.5%). In addition, a slight (P = 0.055) trend towards a higher
      frequency of micronucleated binucleate cells was observed in the second sampling
      for both the exposed and control subjects. As such findings suggest technical
      variation in the cytogenetic parameters, the small difference observed in SCEs
      for the pharmacists between the two samplings was probably not related to the
      cytostatics exposure. No statistically significant differences were observed for
      any of the cytogenetic parameters in comparisons between the pharmacists and the
      referents. The findings suggest that caution should be exercised in comparing
      results obtained from two different samplings in prospective cytogenetic studies.

PMID- 7527910
TI  - Shoulder-hand syndrome in cervical spinal cord injury.
AB  - To characterize the occurrence of shoulder-hand syndrome (SHS) complicating the
      rehabilitation of patients with cervical spinal cord injury, we reviewed the
      medical records of 43 consecutive patients admitted to the Burke Rehabilitation
      Center with cervical spinal cord injury, focusing on the clinical features of
      SHS: shoulder pain, hand/wrist pain, edema, vasomotor changes, trophic changes
      and osteoporosis on x-ray. Twenty-seven patients (63%) had three or more features
      of SHS. The number of features correlated with age (r = 0.495, p = 0.0007), but
      not with the presence of upper or lower motor neuron findings in the arms, or
      with autonomic dysfunction. Twenty-three of 25 (92%) SHS patients with adequate
      follow up had satisfactory resolution of symptoms with conservative therapy (i.e.
      neither systemic corticosteroids nor stellate ganglion block), but only after a
      mean of 121 days (range 42-274 days).

PMID- 7527909
TI  - RNA processing. Splicing in space.

PMID- 7527911
TI  - Successful balloon dilatation of ascending vein stenosis in obstructed
      supracardiac total anomalous pulmonary venous connection.
AB  - A newborn infant presenting with severe hypoxia and pulmonary edema was found to
      have supracardiac total anomalous pulmonary venous connection (TAPVC). There was
      a severe localized stenosis (gradient > 30 mmHg) of the vein ascending from the
      pulmonary venous confluence. Balloon dilatation of the stenosis provided
      immediate and effective relief of the obstruction (gradient 4 mmHg) until surgery
      was performed. In sick neonates with discretely obstructed anomalous pulmonary
      venous connection, short-term hemodynamic stability may be achieved by balloon
      angioplasty of the site of obstruction.

PMID- 7527912
TI  - Balloon occlusion scintigraphy of aortopulmonary collaterals.
AB  - We evaluated two children with pulmonary atresia for coil embolization of
      aortopulmonary collateral vessels after placement of palliative aortopulmonary
      shunts. To determine vessel distribution and lung perfusion prior to collateral
      embolization, perfusion scintigraphy with technetium 99m-labeled macroaggregated
      albumin assessed pulmonary blood flow before and after balloon wedge catheter
      occlusion of the collaterals. In the first patient we found no perfusion defect
      during collateral occlusion, and we proceeded with embolization. In the second
      child, perfusion scintigraphy during occlusion of the collateral vessels
      demonstrated a filling defect, and embolization was not performed, thus avoiding
      the creation of a potential perfusion defect in this patient. Assessing the
      physiologic significance of aortopulmonary collateral vessels by utilizing
      temporary balloon occlusion of the collateral vessels and concurrent perfusion
      scintigraphy as an adjunct to selective angiography can provide a significant
      contribution to the safety and accuracy of coil embolization.

PMID- 7527913
TI  - Loss and gain of chromosomes 1, 18, and Y in prostate cancer.
AB  - Nuclear suspensions of 42 prostate carcinoma specimens obtained at surgery were
      used to investigate loss and gain chromosomes 1, 18, and Y by fluorescence in
      situ hybridization (FISH) with centromere-specific probes. The outcome of FISH
      analysis was correlated with clinical parameters and the relationship between DNA
      FCM (ploidy at cellular level) and FISH (ploidy of individual chromosomes) was
      assessed. Significant loss of chromosomes 1 and 18 was infrequent (respectively,
      three and five cases), but 53% of the tested specimens showed loss of Y. Loss was
      not correlated with DNA ploidy. Significant gain occurred in 36% (chromosome 1),
      63% (chromosome 18), and 28% (Y) of the specimens. Gain of chromosome 18 was
      shown in DNA diploid (7/14) and aneuploid tumors (18/26), while gain of
      chromosomes 1 and Y was nearly restricted to DNA aneuploid specimens. Significant
      unbalance between these chromosomes occurred in 11 cases. Most cases which had
      significant gain of chromosome 1 or 18 showed trisomic as well as tetrasomic
      cells. Simultaneous loss of some and gain of other investigated chromosomes is
      suggestive of clonal heterogeneity and/or multiclonality. This was observed in
      eight tumors. Correlation between DNA-FCM and FISH was best for the Y chromosome.
      DNA-FCM showed more aberrant histograms with increasing stage and grade of
      tumors. The presence of numerical aberrations of the investigated chromosomes
      however, seemed independent of clinical grade or stage.

PMID- 7527914
TI  - Late mitosis/early G1 phase and mid-G1 phase are not hypersensitive cell cycle
      phases for neoplastic transformation of HeLa x skin fibroblast human hybrid cells
      induced by fission-spectrum neutrons.
AB  - A two- to threefold increase in the rate of neoplastic transformation in cells
      irradiated at a dose rate of 0.22 cGy/min with fission-spectrum neutrons compared
      to that at 10.7 cGy/min has been confirmed with the use of alkaline phosphatase
      chromogenic substrate Western Blue staining to detect foci of neoplastically
      transformed cells through their expression of a tumor-associated antigen, the end
      point of the HeLa x skin fibroblast human hybrid cell transformation assay. To
      investigate whether the inverse dose-rate effect is due to the existence of a
      period in the cell cycle in which cells are significantly more sensitive to
      neoplastic transformation than in the rest of the cell cycle, as has been
      postulated previously (Rossi and Kellerer, Int. J. Radiat. Biol. 50, 353-361,
      1986; Brenner and Hall, Int. J. Radiat. Biol. 58, 745-758, 1990; Elkind, Int. J.
      Radiat. Biol. 59, 1467-1475, 1991), we compared the sensitivity of late
      mitotic/early G1-phase and mid-G1-phase cells with that of asynchronous cells.
      The rationale for examining these particular cell cycle phases was based on the
      fact that mitosis has been hypothesized to be a candidate for the extremely
      sensitive period, and on a preliminary report that mid-G1-phase C3H 10T1/2 cells
      may exhibit enhanced sensitivity for neutron-induced transformation. A nominal
      dose of 45 cGy of fission-spectrum neutrons was delivered at approximately 10
      cGy/min. The data indicate that neither late mitotic/early G1-phase nor mid-G1
      phase cells are significantly more sensitive than asynchronous cells. Further,
      the dependence on the phase of the cell cycle for neoplastic transformation of
      CGL1 cells induced by fission-spectrum neutrons is different from that previously
      demonstrated for gamma radiation, where late-mitotic cells were approximately
      five times more sensitive than mid-G1-phase and asynchronous cells (Redpath and
      Sun, Radiat. Res. 121, 206-211, 1990).

PMID- 7527915
TI  - [Angiogenetic capacity of breast neoplasms and correlation with color-Doppler
      semiology].
AB  - The authors correlated the presence/absence of color signal-as shown by color
      Doppler ultrasonography (CDUS) in 22 cases of breast carcinoma-with lesion
      angiogenesis potentials, as evaluated in the histologic sections with the
      determination of the microscopic angiogenesis grading system (MAGS) index. In all
      4 cases in which CDUS showed no color signal, MAGS index value exceeded 30, which
      is suggestive of high neoplastic neoangiogenesis potentials. In contrast, in 17
      of 18 cases positive to CDUS, MAGS index value remained below 30 and the
      microscopic analysis showed the presence of many fresh vessels more than 1 mm in
      caliber. Consequently, the presence of color signals at CDUS exams may be related
      to the features of tumor feeding vessels and therefore a negative CDUS exam
      cannot be considered as a reliable sign to exclude a malignant lesion.

PMID- 7527916
TI  - [Comparison between 2 techniques of screening for prostatic carcinoma. Rectal
      exploration and transrectal ultrasonography vs. prostate specific antigen].
AB  - We report the results of two pilot studies for the early detection of prostatic
      carcinoma in resident men aged 60-75 years, using combined digital rectal
      examination (DRE) and transrectal ultrasonography (TRUS) versus prostate-specific
      antigen (PSA; cutoff: 4 ng/ml) as screening tests. Both screening protocols
      exhibited high cancer detection rates (DRE + TRUS = 1.82%, PSA = 1.67%), with a
      high prevalence/incidence ratio (observed/expected ratio: DRE-TRUS = 13.8:1, PSA
      = 11.3:1) and a diagnostic anticipation of about 6-7 years. Stage (DRE + TRUS: A
      = 0%, B = 69%, C-D = 31%; PSA:A = 14%, B = 77%, C-D = 9%) and grading
      distribution (no case with Gleason score < 5) suggests that most screen-detected
      cancers were clinically assessable but the extent of overdiagnosis of latent
      carcinomas cannot be estimated. Both screening protocols proved to be cost
      effective (biopsy rate: DRE + TRUS = 2.7%, PSA = 2.8%; cost per screened subject:
      DRE + TRUS = L. 33,750, PSA = L. 30,400; cost per cancer detected: DRE + TRUS =
      L. 1,854,000, PSA = L. 1,817,500) but screening by PSA was much better accepted
      (attendance rate: DRE + TRUS = 33.7%, PSA = 66.9%), which makes it the screening
      test of choice for controlled studies on screening efficacy. This study allows no
      definitive conclusions to be drawn on screening efficacy but confirms only that
      screening is feasible at a reasonable cost and yields high diagnostic
      anticipation. Whether this benefits the screened population is currently debated
      and needs to be confirmed by controlled studies. Screening may have upsetting
      negative outcomes such as overdiagnosis, overtreatment, increased treatment
      related mortality rates and worsened quality of life, and there is no evidence
      supporting the recommendation of screening as a routine practice.

PMID- 7527917
TI  - [The microbiological considerations in the Leuconostoc-sugar-dextran-health
      relationship].

PMID- 7527918
TI  - [The acute-phase response and the anti-infectious defense].

PMID- 7527919
TI  - [Morphological evidence of purinergic transmission at the level of the
      laterovertebral sympathetic chain in rats].

PMID- 7527920
TI  - Transurethral incision of the prostate for the treatment of benign prostatic
      hyperplasia.

PMID- 7527921
TI  - Transurethral ultrasound-guided laser induced prostatectomy (TULIP) for the
      treatment of BPH.

PMID- 7527923
TI  - Contact laser ablation of the prostate for the treatment of benign prostatic
      hypertrophy.

PMID- 7527922
TI  - Right-angle free beam lasers for the treatment of benign prostatic hyperplasia.
AB  - When comparing the efficacy of VLAP to TURP, the existing data are not entirely
      consistent. Several studies conclude that the two procedures have equivalent
      efficacy with respect to AUA symptom score, peak flow rate, and reduction of
      postvoid residual urine volume. None of these studies are designed to control for
      patient or investigator bias and generally only mean values are compared. To
      date, our study is the only double-blind, randomized trial that compares VLAP to
      TURP. Although the laser procedure was an effective alternative, it was not as
      effective as TURP as measured by the AUA symptom score, reoperation rate, or the
      patients' global assessment of symptomatic improvement. To be a useful procedure,
      it is not essential that the efficacy be equivalent to TURP, but it is clearly
      preferred particularly because an anesthetic is usually required. When comparing
      the efficacy of these two procedures, one cannot help asking an obvious question:
      What is the chance that the first attempt at a new procedure (VLAP), with
      relatively little prior testing, would be equally effective to a procedure (TURP)
      that has been performed hundreds of thousands of times and modified during the
      past 50 years? It should not be too disappointing or surprising that our data
      show the TURP to be more effective. These data represent the first attempts at
      laser treatment for BPH. Although it is an easy procedure for a urologist to
      learn, the optimal technique has not been defined. It is very likely that
      improvements in technology and technique will improve the efficacy while
      maintaining safety.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7527924
TI  - Microwave hyperthermia for the treatment of benign prostatic hyperplasia.

PMID- 7527925
TI  - Microwave thermotherapy for the treatment of benign prostatic hyperplasia.

PMID- 7527926
TI  - Prostatic urethral stents.

PMID- 7527927
TI  - High-intensity focused ultrasound for the treatment of benign prostatic
      hypertrophy.

PMID- 7527928
TI  - Transurethral needle ablation of the prostate (TUNA): pathological, radiological
      and clinical study of a new office procedure for treatment of benign prostatic
      hyperplasia using low-level radiofrequency energy.

PMID- 7527930
TI  - Clinical and laboratorial features of visceral toxocariasis in infancy.
AB  - Forty children with a diagnosis of Visceral Toxocariasis were evaluated
      prospectively from February 1982 to June 1989. Diagnosis was established by
      clinical, laboratory and serological (ELISA - ES Toxocara canis antigen)
      evaluations. A great clinical polymorphism was found in our patients, ranging
      from unspecific or absent manifestations to an exuberant symptomatology. The
      laboratory findings were: leukocytosis, eosinophilia and elevation of serum
      gammaglobulin and isohemagglutinin levels. No significant relationship between
      clinical findings and laboratory parameters was found. Serology (ELISA) was a
      method of great diagnostic support but did not show a correlation with clinical
      and laboratory findings in this study. There was a significant relationship
      between pulmonary manifestations and the presence of signs and/or symptoms, when
      the patients were sent to us. Our findings, especially the high incidence of
      pulmonary manifestations, suggest that Visceral Toxocariasis has to be included
      in the differential diagnostic of children with pulmonary manifestations,
      characteristic epidemiological data and associated eosinophilia.

PMID- 7527932
TI  - Identical VHD and DJH junctions in monoclonal antibodies derived in response to
      dextran B512 could be the result of developmental selection.
AB  - We describe here the CDR3s of a collection of monoclonal antibodies (MoAb) with
      specificity for the carbohydrate dextran B512 produced in the mouse strain
      C57BL/6. In spite of the postulated mechanisms for variability in this region, a
      high proportion of these monoclonals displayed identical VHD (24/30) and DJH
      (21/30) junctions and 21 of them were identical in the whole CDR3. These 21
      independently generated identical CDR3s could be ordered in eight groups
      indicating that not a particular CDR3, but instead the mechanism for generating
      identical junctions was preserved. Two of the CDR3s in this study were found to
      be identical to the CDR3 of the monoclonal B1-8 produced in C57BL/6 in response
      to proteins bearing the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP). This and
      other parameters support the notion that the generation of identical junctions
      could be independent of antigenic selection. We also report here the association
      between JH usage and amino acid (aa) residues at the VHD and DJH junctions. Since
      these MoAb were generated in response to dextran B512, immunoglobulin
      conformation has to be compatible with antigen binding. Nevertheless, no aa
      residue of CDR3 could be directly related to antigen binding. We postulate
      therefore, that the observed selection of CDR3s could be directed to the
      production of variable regions with protein configuration most suitable with
      immunoglobulin folding and may occur prior to antigenic selection. Selection for
      junctional residues in relation to JH usage and the generation of identical CDR3s
      are probably different events. Possible genetic mechanisms operating for CDR3
      construction and/or selection by cellular ligands are discussed.

PMID- 7527931
TI  - Effects of different density gradient separation techniques on neutrophil
      function.
AB  - Investigation of the pathogenesis of inflammatory diseases has involved
      assessment of polymorphonuclear leukocyte (PMN) activity and a variety of
      techniques for separating PMNs from whole blood have been described. In this
      study the effects of Percoll gradient, Ficoll-Hypaque/Dextran sedimentation
      (FH/DS) and Mono-Poly Resolving Medium (M-PRM) on activation and function of PMNs
      were compared. All three separation techniques gave similar cell yield and
      purity. The mean (+/- SEM) percentage of cells demonstrating pseudopodia
      formation for Percoll, FH/DS and M-PRM were 39 +/- 9, 57 +/- 6 and 63 +/- 5,
      respectively, while superoxide release from resting cells was 1.9 +/- 0.9, 7.2 +/
      3.5 and 11 +/- 4.8 pmols per 10(6) cells min-1, respectively, indicating that
      activation of cells during separation may be less with Percoll compared to the
      other methods. The functional capacity of the cells to respond to a stimulus was
      similar for all methods as indicated by similar EC50 values for chemotaxis to
      zymosan-activated serum and similar superoxide production induced by
      tetradecanoyl phorbol acetate. All three separation techniques produce
      functionally active PMNs of high purity but the use of Percoll gradients may be
      preferable when a quick method of separation which causes minimum pre-activation
      of PMNs is required.

PMID- 7527929
TI  - Pathologic classification of soft tissue sarcomas.
AB  - A number of immunological markers and chromosomal abnormalities are described to
      aid in the diagnosis, prognosis and management of soft tissue sarcomas. Although
      the chromosomal abnormalities may be specific in some cases, they have only been
      reported in small series or single cases and their significance has not yet been
      established. None of the immunological markers described is either entirely
      specific or sensitive for a particular tumor type, and virtually none of these
      immunological reagents is currently approved for diagnostic use despite their
      widespread applications in pathology. They function in a supporting role to
      conventional tissue pathology, grading, and pathological and clinical staging of
      soft tissue sarcomas. Antibodies employed as an aid in diagnosis of soft tissue
      tumors should always be run in panels and never as single tests. New
      immunological markers and chromosomal abnormalities in soft tissue sarcomas
      should be carefully evaluated for their specificity and sensitivity and their
      usefulness in diagnosis and prognosis.

PMID- 7527934
TI  - Direct evidence for SAA deposition in tissues during murine amyloidogenesis.
AB  - To study the mechanism of amyloid deposition, the nature of amyloid proteins
      formed in experimental murine amyloidosis, was examined. Spleen specimens, 15-60
      mg, were homogenized and extracted using aqueous acidic acetonitrile, in a
      recently developed procedure, making it possible to obtain amyloid proteins from
      minute amounts of tissue. The extracted material, 1.5-4 mg, was analysed by
      Western blotting and ELISA using antibodies recognizing differentially proteins
      AA and SAA. Two immunoreactive proteins of 8 and 12 KDa were isolated and
      subjected to amino acid analysis and N-terminal sequence determination. The
      results of immunochemical and chemical examination showed that the 8 and 12 KDa
      proteins represented proteins AA and SAA, respectively. The data obtained provide
      new direct evidence for SAA in tissues during murine amyloidogenesis.

PMID- 7527933
TI  - The influence of branched polypeptide carriers on the immunogenicity of predicted
      epitopes of HSV-1 glycoprotein D.
AB  - To investigate the role of synthetic polypeptide carriers in inducing an epitope
      specific immune response relevant for vaccine design, peptides comprising two
      distinct regions of herpes simplex virus type I glycoprotein D (1-23 and 273-284)
      have been conjugated to the branched polypeptides with polylysine backbone,
      poly[L-Lys-(DL-Alam)] (AK), or poly[L-Lys-(Leui-DL-Alam)] (LAK) and to keyhole
      limpet haemocyanin (KLH). The magnitude, fine specificity and isotype
      distribution of the conjugate-, peptide-and carrier-specific antibody responses
      were characterized in immunized BALB/c and CBA mice. Conjugates containing the
      polypeptide carrier AK were the most effective in inducing HSV gD-peptide
      specific antibody responses while KLH peptide conjugates resulted in conjugate
      specific antibody responses without measurable peptide specificity. The efficacy
      of AK-peptide conjugates was verified by the dominant appearance of peptide
      specific antibodies belonging to functionally efficient IgG isotopes, accompanied
      by low levels of carrier specific antibody responses. Preimmunization of BALB/or
      CBA mice with AK conjugates comprising the 1-23 or 276-284 HSV peptides resulted
      in prolonged survival of animals infected with a lethal dose of infectious HSV-1.
      The potency of these conjugates in eliciting a protective immune response shows a
      close correlation with the relative levels of conjugate-induced virus-specific
      antibodies and the neutralizing activity of sera as measured in preimmunized
      survivors.

PMID- 7527935
TI  - Structural specificity of MHC-unrestricted recognition of HCMV-infected target
      cells by human CD56+NK and LAK cells.
AB  - Structural specificity of binding and cytolysis of HCMV-infected human foreskin
      fibroblasts (HFF) by human NK and LAK cells was studied in inhibition assays. A
      sample of 60%-deacetylated alpha-D mannose penta-acetate was used as inhibitor
      that was previously shown to specifically inhibit binding and cytolysis of tumour
      target cells by human NK and LAK cells. We found now that cytolysis of HCMV
      infected HFF was inhibited in a dose-dependent manner showing complete inhibition
      at concentrations above 640 nmoles/ml mannose acetate. This effect on cytolysis
      was based on inhibition of conjugate formation between virus-infected cells and
      CD56+NK and LAK cells. In the presence of mannose acetate (640 nmoles/ml)
      conjugate formation of virus-infected cells was suppressed down to the level of
      uninfected cells. The latter showed residual conjugate formation on the basis of
      adhesive interactions with chemospecifity other than for mannose acetate, which
      were not capable of triggering cytolytic reactions. Coculturing of target cells
      with LAK cells appeared to induce expression of additional mannose acetate
      specific target sites yielding increases of conjugate formation and cytolysis.

PMID- 7527936
TI  - Three new cross-reacting idiotopes as markers for the products of two distinct
      human VH3 genes expressed in the early repertoire.
AB  - This article describes characterization of three new cross-reacting idiotopes, as
      recognized by mouse MoAbs, on human antibodies utilizing VH3 genes that are
      expressed in the early repertoire. Two of the mouse MoAbs (3H7 and 3H1) were
      raised against a human MoAb utilizing the DP47 (VH26) VH3 gene, whilst the third
      (7B4) was raised against a DP46 (GLSJ2) gene product. Evidence for the anti
      idiotypic specificity of the mouse MoAbs was provided by their reactivity with
      the immunizing IgM, but not with Fc mu, and by their specific inhibition of the
      binding between each immunizing antibody and its antigen. The three anti
      idiotypic MoAbs were shown to be VH-specific reagents by the independence of
      their reactivity upon the L-chain type, or the antigenic specificity of the human
      MoAbs tested. Specificity of each mouse MoAb for VH3 gene-products was
      demonstrated by its sole cross-reactivity with VH3 proteins. Each anti-Id had a
      different reactivity pattern with a panel of MoAbs utilizing different VH3 genes.
      By relating the VH sequences of the tested VH3 proteins to their germline
      counterparts, 3H7 and 3H1 appeared to be specific for DP47-encoded proteins,
      although 3H1 had weak cross-reactivities with a few other VH3 gene-products. 7B4
      appeared to be specific for antibodies utilizing DP46-related genes. Both 3H7 and
      3H1 were also completely different to B6 and D12, two previously described MoAbs
      that also recognize VH3 proteins. Although 7B4 was similar to B6 and D12 in its
      binding to DP46-related gene products, B6 and D12 additionally recognized non
      DP46-related proteins and were thus different to 7B4.

PMID- 7527938
TI  - Platelet-activating factor-induced endothelial cell expression of adhesion
      molecules and modulation of surface glycocalyx, evaluated by electron
      spectroscopy chemical analysis.
AB  - PAF synthesized by or added to the endothelial cell monolayer has as first target
      the endothelium itself, inducing the expression of GMP-140 on the cell surface
      and qualitative alterations in the composition of glycocalyx. As seen by ESCA,
      sulfated chemical groups were significantly reduced after PAF stimulation. This
      reduction depended on selective loss of sulfated proteoglycans that were released
      into the supernatant. The alteration of glycocalyx may favor functional exposure
      of GMP-140 and of PAF on the surface of endothelial cells and may reduce charge
      repulsive forces between cells. PAF associated with endothelial cell surface has
      as second target PMNs and stimulates in cooperation with GMP-140, the functional
      activation of PMN CD11-CD18 adhesion molecules.

PMID- 7527937
TI  - An alternative to SH2 domains for binding tyrosine-phosphorylated proteins.
AB  - Src homology 2 (SH2) domains bind specifically to tyrosine-phosphorylated
      proteins that participate in signaling by growth factors and oncogenes. A protein
      domain was identified that bound specifically to the tyrosine-phosphorylated form
      of its target protein but differs from known SH2 sequences. Phosphotyrosine
      binding (PTB) domains were found in two proteins: SHC, a protein implicated in
      signaling through Ras; and SCK, encoded by a previously uncharacterized gene. The
      PTB domain of SHC specifically bound to a tyrosine-phosphorylated 145-kilodalton
      protein. PTB domains are an alternative to SH2 domains for specifically
      recruiting tyrosine-phosphorylated proteins into signaling complexes and are
      likely to take part in signaling by many growth factors.

PMID- 7527939
TI  - HDR intraluminal brachytherapy for lung tumours--a case report.
AB  - The lung is a common site for cancer to occur, for both primary as well as
      metastases. The presence of such tumours can give rise to symptoms such as
      haemoptysis, cough, breathlessness and pneumonia. In most cases, treatment is
      strictly for palliation. We present a case report of a patient with an
      endobronchial metastasis from a primary hypernephroma which recurred following
      external beam radiotherapy. He was treated with a single fraction of intraluminal
      brachytherapy to a dose of 10Gy at 1 cm from the axis on a High Dose Rate Ir192
      Remote Afterloading Machine. There were no adverse effects following treatment.
      On follow-up 7 months later, the patient did not have any further recurrence of
      breathlessness although his disease had progressed at other sites.

PMID- 7527940
TI  - The 'TRAP' sequence--life threatening consequences to the pump twin.
AB  - The acardius foetal malformation is a rare abnormality occurring in monozygotic
      multiple pregnancies. This is a case report of a pair of twins with the "twin
      reversed arterial perfusion (TRAP)" sequence and its complications. The recipient
      twin was born acardius acephalus. The pump twin had problems of prematurity,
      disseminated intravascular coagulation, sclerema and right ventricular
      hypertrophy. On follow-up at seven months he has failure to thrive, spastic
      quadriplegia and developmental delay. An awareness of the TRAP sequence may lead
      to better antenatal diagnosis and optimal management of the twin pregnancy.

PMID- 7527941
TI  - [Immunohistochemistry--more than a staining method].
AB  - Immunohisto/cytochemistry is a versatile and potent in situ molecular probing
      method that is increasingly applied both for diagnostic purposes and as a
      research tool in immunology, pathology, cell biology, embryology, cell kinetics
      and carcinogenesis. In theory, the methodology is not complicated, but in
      practice it presents many surprising difficulties. Such problems can be masked by
      the uncritical use of apparently simple commercial kits. It is important to be
      aware of the advantages and drawbacks of the available technical modifications.
      This is also true with respect to the choice of immunological reagents, whether
      polyclonal or monoclonal antibodies are employed. Even a monoclonal antibody can
      produce spurious results, with a potential for severe misinterpretations.

PMID- 7527942
TI  - [Immunohistochemical tumor diagnosis--possibilities and limitations].
AB  - Immunohistochemical techniques are becoming of steadily increasing importance as
      an adjunct in the diagnosis of tumours. Such investigations should always be
      integrated with clinical variables and routine histopathological findings, and at
      the same time be based on immunological expertise. There are several pitfalls in
      immunohistochemistry, regardless of whether monoclonal or polyclonal antibody
      reagents are used. In addition, the handling of the tissue specimens, both by the
      clinician and by the pathologist, and how the tissue sections are prepared, are
      of paramount importance for the immunohistochemical result. Whether this
      methodology is of any diagnostic help, or rather the reverse, often depends on
      how the pathologist and the clinician are able to evaluate aberrant
      immunohistochemical results obtained in the actual diagnostic setting.

PMID- 7527943
TI  - [Microwave oven in immunohistochemistry. An important tool for determination of
      antigens in formalin-fixed and paraffin-embedded tissue].
AB  - Immunocytochemical methods are important tools for identifying antigens in tissue
      sections and cell smears. Some antigens were retrieved in formalin-fixed and
      paraffin-embedded tissues by means of a microwave technique. This method also
      increased the sensitivity of the immunohistochemical detection of several other
      antigens. Altogether, microwave boiling of the tissue sections in citrate buffer
      clearly improved the immunoreactivity for cytokeratin 18, oestrogen receptor, Ki
      67 protein, PCNA, p53 protein, retinoblastoma gene protein and c-erbB-2 protein.
      This new technique, which can be applied in every pathology laboratory, will
      facilitate the application of immunohistochemical methods for research and
      diagnostic work.

PMID- 7527944
TI  - Effects of divided doses of steroids on side effects, cytokines, and activation
      of complement and granulocytes, coagulation and fibrinolysis after OKT3.

PMID- 7527945
TI  - Severe neutropenia after renal transplantation and its reversal with granulocyte
      colony-stimulating factor.

PMID- 7527946
TI  - Nephrotoxity of FK 506: a preliminary study on comparative aspects of FK 506 and
      cyclosporine nephrotoxicity.

PMID- 7527948
TI  - Distinct intragraft cytokine gene expression patterns during acute hepatic
      rejection under cyclosporine versus FK 506 primary immunosuppression.

PMID- 7527947
TI  - Gastrointestinal toxicity associated with FK 506 in liver transplant recipients.

PMID- 7527949
TI  - Cyclosporine in treatment of progressive systemic sclerosis: clinical and
      immunologic findings.

PMID- 7527950
TI  - Potential role of 1,25(OH)2 vitamin D3 as a dose-reducing agent for cyclosporine
      and FK 506.

PMID- 7527952
TI  - Causes of death following liver transplantation in FK 506- and cyclosporine
      treated patients.

PMID- 7527951
TI  - Severe neurotoxicity after liver transplantation: association between FK 506
      therapy and hepatitis C virus disease.

PMID- 7527954
TI  - New trends in clinical immunosuppression.

PMID- 7527953
TI  - Neurological disorders in liver and kidney transplant recipients.

PMID- 7527955
TI  - Unresponsiveness to rat cardiac allografts induced by intrathymic injection of
      donor bone marrow cells and short course of immunosuppression.

PMID- 7527956
TI  - Immunosuppression conversion for relief of side effects.

PMID- 7527957
TI  - FK 506 rescue therapy for irreversible airway rejection in heart-lung transplant
      recipients: report on five cases.

PMID- 7527959
TI  - Efficacy of leflunomide in combination with current immunosuppressive agents in
      rat cardiac allotransplantation.

PMID- 7527958
TI  - The influence of OKT3 on expression of lymphocyte adhesion molecules in vitro.

PMID- 7527960
TI  - Reduced incidence of acute, refractory acute, and chronic rejection after liver
      transplantation with FK506-based immunosuppression. European FK506 Multicentre
      Liver Study Group.

PMID- 7527962
TI  - Pharmacokinetics, dosing principles, and blood level monitoring of FK506.

PMID- 7527961
TI  - Optimised first-line FK506-based protocols in liver transplantation: experience
      from the University Hospital Rudolf Virchow, Berlin.

PMID- 7527963
TI  - Renal function in liver transplant patients receiving FK506 or cyclosporin A
      immunosuppressive therapy.

PMID- 7527965
TI  - Early graft function in liver transplantation patients.

PMID- 7527964
TI  - Modes of action of FK506, cyclosporin A, and rapamycin.

PMID- 7527968
TI  - 15-Deoxyspergualin inhibits nitric oxide production in the BB/W rat: mechanism
      for inhibition of islet cell dysfunction in diabetes and transplantation.

PMID- 7527967
TI  - Donor bone marrow cell infusion without recipient cytoablation induces acceptance
      of rat islet allografts.

PMID- 7527969
TI  - Hepatocytes or liver nonparenchymal cells plus FK 506 prolong liver xenograft
      survival.

PMID- 7527970
TI  - Polymerase chain reaction-based assay to assess the success of myoblast
      transplantation in mdx mice.

PMID- 7527975
TI  - Neo-cartilage generated from chondrocytes isolated from 100-year-old human
      cartilage.

PMID- 7527974
TI  - Simple method of adult pig pancreatic cell preparation by auto-digestion.

PMID- 7527971
TI  - Islet isolation from slaughterhouse pig pancreata: evidence of in vitro and in
      vivo function.

PMID- 7527973
TI  - Simple dithizone-stained multilayer test for selection of density gradient before
      human islet mass purification.

PMID- 7527972
TI  - Preliminary study of a new method for monitoring viability of transplanted islets
      of Langerhans.

PMID- 7527966
TI  - An effective strategy for decontamination, ex vivo expansion, and storage of
      human fetal liver hematopoietic stem cells.
AB  - The transplantation of human fetal tissue has the potential to cure a variety of
      life-threatening diseases. The strategy for procurement, quality control, and
      functional assessment of human fetal liver HSC may prove useful for the
      transplantation of other fetal tissues. In addition to technical limitations,
      there are ethical and legal issues which need to be resolved before widespread
      use of fetal tissue. Further development of regulatory standards for the
      acquisition and distribution of fetal tissues will foster the application of this
      novel technology.

PMID- 7527976
TI  - Effect of blood content on porcine pancreatic dissociation and islet yield.

PMID- 7527977
TI  - The skin immune system: CD36(+)-dendritic epidermal cell--a putative actor in
      posttransplant immunological events.

PMID- 7527978
TI  - Immunosuppression with FK 506 insures good success of myoblast transplantation in
      MDX mice.

PMID- 7527979
TI  - Neoadjuvant chemotherapy after liver transplantation for hepatocellular
      carcinoma.

PMID- 7527981
TI  - Chemoembolization for hepatocellular carcinoma in cirrhotic patients: assessment
      of efficacy on total hepatectomy specimens.

PMID- 7527980
TI  - Liver transplantation for hepatocellular carcinoma with cirrhosis: the initial
      experience and a preliminary report from the University of Ghent, Belgium.

PMID- 7527984
TI  - Increased rejection after liver transplantation in FK 506-treated patients is
      associated with viral hepatitis C disease.

PMID- 7527982
TI  - Conversion to rescue therapy with FK 506: data from eight liver transplant
      patients.

PMID- 7527983
TI  - Outcome following orthotopic liver transplantation in HBsAg-positive patients
      using short- or long-term immunoprophylaxis.

PMID- 7527985
TI  - Effect of aprotinin on transfusion requirements during repeat sternotomy for
      cardiac transplantation surgery.

PMID- 7527988
TI  - [The immunological indices of guinea pigs modelling Marburg hemorrhagic fever].
AB  - Presents data on changes in nonspecific immunity (interferon, tumor necrosis
      factor, natural killers), spontaneous and mitogen-induced lymphocyte
      proliferation in the course of development of experimental Marburg fever.
      Demonstrates the effects of the said factors and interleukin-2 on the course of
      the fever and their role in a lethal outcome of the disease.

PMID- 7527987
TI  - Shock wave induced endothelial damage--in situ analysis by confocal laser
      scanning microscopy.
AB  - For more than a decade, extracorporal shock wave lithotripsy has been a standard
      clinical method for the treatment of urinary stones. However, side effects that
      are likely to be correlated to vessel damage can often be observed using
      noninvasive diagnostic techniques, e.g., magnetic resonance imaging. To avoid
      side effects it is useful to understand the interaction between shock waves and
      the vascular system. In particular, this is important in view of new applications
      like gallstone lithothripsy. In the present study, we exposed human umbilical
      vessels to electromagnetically generated ultrasound shock waves to analyze
      subsequent alterations of their endothelial layer. Following en face preparation
      and fluorescent staining, the endothelium was examined in a confocal laser
      scanning microscope. Endothelial cells of the shock wave exposed vessels revealed
      permeabilization of plasma membranes and mitochondrial alterations as potentially
      lethal damage. An increase in the number of stress fibres may indicate functional
      changes possibly influencing vessel wall permeability.

PMID- 7527989
TI  - [The isolation and characteristics of monoclonal antibodies to the glycoprotein
      GII of Aujeszky's disease virus and their use for the epitopic mapping of GII].
AB  - A panel of 24 different monoclonal antibodies (MAB) to Aujeszky's disease virus
      (ADV) proteins was prepared. Seven MABs were directed to ADV glycoprotein GII (6
      MABs to GIIc chain and 1 MAB to GIIb chain). GII epitope mapping with the
      resultant MABs was carried out. Four ADV GII epitopes were detected: epitopes A,
      B, and C located on GIIc chain and epitope D located on GIIb chain. Epitope B
      overlaps epitopes A and C which do not overlap each other, epitope D does not
      overlap other epitopes. Epitopes A, B, and C are located in a restricted area of
      GIIc chain which seems to be one of GII immunodominant regions. The detected
      epitopes are mainly conformational, for they are sensitive to denaturation. Of
      all MABs obtained more than 30% were directed to ADV GII. This indicates that GII
      is one of the most important ADV antigens. All the seven MABs to GII interacted
      with all tested ADV strains (K. Arsky, VGNKI, BUK, and NIA-4), this being in line
      with the data on a highly conservative nature of ADV GII.

PMID- 7527990
TI  - Thyroxine excess and pregnancy.
AB  - Pregnancy is characterised by a physiological increase in bound thyroxine but
      normal values of free hormone. Human chorionic gonadotrophin (hCG may stimulate
      the thyroid to produce hyperemesis gravidarum (with mild to moderate
      hyperthyroidism) or result in high thyroid hormone levels associated with
      gestational trophoblastic disease. Hyperthyroidism occurring during pregnancy is
      usually due to Graves' disease and must be treated to prevent congenital
      anomalies, low birth weight and premature labour. Thionamide drugs should be used
      with a preference for propylthiouracil (PTU) and continued in low doses up to
      labour. Breast feeding is possible in patients on low dose PTU. In the management
      of hypothyroidism during pregnancy thyroxine dose may require to be increased but
      excess dosage should be avoided because of its unwanted effects on foetal
      cerebral maturation. Neonatal hyperthyroidism due to transplacental passage of
      thyroid stimulating antibodies (TsAb) should be checked for in pregnant patients
      with autoimmune thyroid disease. As antithyroid drugs cross the placenta they may
      be used as therapy in this condition. Prevention of neonatal goitre is vital.
      Postpartum development of hyperthyroidism may be due to an exacerbation of pre
      existing Graves' disease, development of new Graves' hyperthyroidism or
      postpartum thyroiditis with transient hyperthyroidism. Differentiation by
      measurement of TsAb and thyroidal iodine uptake is important because of
      therapeutic considerations.

PMID- 7527991
TI  - Thyroid hormone excess and osteoporosis.
AB  - Current thinking and available clinical data on the relationship between
      hyperthyroidism and bone disease are discussed. Data are also presented on TSH
      suppressive and non-suppressive thyroid hormone therapy and its effect on bone.
      Although these data are clearly inconsistent, some risk factors for thyroid
      hormone induced osteopenia seem to be accepted: long standing, clinically
      manifest hyperthyroidism (a very rare disorder today because of early diagnosis
      and appropriate therapy), old age, menopause and total thyroidectomy. Thyroid
      hormone therapy (whether TSH-suppressive or not) has not been proven so far to
      lead to manifest osteoporosis.

PMID- 7527992
TI  - [Errors in the clinical staging of prostatic cancer].
AB  - The relationship between the clinical and pathological stages of clinically
      localized prostate cancer (PCa) was analyzed in 68 patients. All of then
      underwent ilio-obstructive lymphadenectomy and node affectation was found in 16
      patients (23%). Out of 64 patients undergoing radical prostatectomy, 23 (36%)
      presented invasion of prostate capsule and/or seminal vesicle infiltration. Of
      the total 68 patients, 28 (41%) showed local dissemination and/or nodular
      affectation. A direct correlation was seen between clinical stage and both
      incidence of local dissemination and nodular affectation. Pre-operative PSA and
      tumoral grade were correlated to the pathological stage.

PMID- 7527993
TI  - [Cultural and linguistic validation, in Spanish, of the International Prostatic
      Symptoms Scale (I-PSS)].
AB  - Formal presentation of the cultural and linguistic validation, in Spanish, of the
      International Prostatic Symptoms Scale (I-PSS). The process for the official
      translation into Spanish of the questionnaire on prostatic symptomatology and
      quality of live derived from urinary symptoms, has followed a methodology common
      to several countries (UK, Italy, Norway, The Netherlands and Spain) which
      consisted in: translation into Spanish of the original American-English version
      published by the WHO in 1992, by two independent bilingual urologists; re
      translation into English, checking any conceptual and semantic changes that had
      caused difficulties in the process of translation/re-translation; final choice of
      the text by an International Committee based both on the data provided by the
      above process and the experience of the Central Committee accrued over their
      relationships with the various National Committees. The resulting text was
      applied to 33 patients with prostate disease and 12 controls, individually
      recording any difficulty of interpretation and choice of answer observed for each
      of the questions. The final text herewith presented constitutes the official
      reference for the Spanish translation of the International Prostatic Symptoms
      Scale (I-PSS) which should be used for future symptomatic evaluations. The
      purpose of this cultural and linguistic validation is to secure that the
      application of these scales provides comparable and consistent numerical results
      in those countries where the translation has not been officially validated.

PMID- 7527994
TI  - [Prostatic adenoma and specific prostatic antigen].

PMID- 7527986
TI  - The influence of donor and recipient strains in isolated small bowel
      transplantation in rats.

PMID- 7527995
TI  - Medical therapy for benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a common clinical entity in elderly men. We
      review the epidemiology of BPH and the mechanisms by which it causes bladder
      outlet obstruction. The currently available medical therapies are examined with
      respect to mechanism of action, effectiveness, side effects, and cost. They are
      briefly compared with the more traditional treatment options of watchful waiting
      and transurethral prostatectomy. A logical approach to the treatment of
      symptomatic BPH is discussed.

PMID- 7527996
TI  - Craniometric variation among modern human populations.
AB  - Previous studies of genetic markers and mitochondrial DNA have found that the
      amount of variation among major geographic groupings of Homo sapiens is
      relatively low, accounting for roughly 10% of total variation. This conclusion
      has had implications for the study of human variation and consideration of
      alternative models for the origin of modern humans. By contrast, it has often
      been assumed that the level of among-group variation for morphological traits is
      much higher. This study examines the level of among-group variation based on
      craniometric data from a large sample of modern humans originally collected by W.
      W. Howells. A multivariate method based on quantitative genetics theory was used
      to provide an estimate of FST--a measure of among-group variation that can be
      compared with results from studies of genetic markers. Data for 57 craniometric
      variables on 1,734 crania were analyzed. These data represent six core areas:
      Europe, Sub-Saharan Africa, Australasia, Polynesia, the Americas, and the Far
      East. An additional set of analyses was performed using a three-region subset
      (Europe, Sub-Saharan Africa, and the Far East) to provide comparability with
      several genetic studies. The minimum FST (assuming complete heritability) for the
      three-region analysis is 0.065, and the minimum FST for the six-region analysis
      is 0.085. Both of these are less than the average FST from genetic studies
      (average estimates of 0.10-0.11). The smaller value of the minimum FST estimates
      is expected since it provides an estimate of FST expected under complete
      heritability. Using an estimate of average craniometric heritability from the
      literature provides an estimate of FST of 0.112 for the three-region analysis and
      0.144 for the six-region analysis. These results show that genetic and
      craniometric data are in agreement, qualitatively and quantitatively, and that
      there is limited variation in modern humans among major geographic regions.

PMID- 7527997
TI  - Influence of cationic antibiotics on phase behavior of rough-form
      lipopolysaccharide.
AB  - The rough-form lipopolysaccharide (LPS) interacted with cationic antibiotic
      polymyxin B and gramicidin S in solution, and showed altered thermotropic phase
      behavior and viscoelasticity. The phase behavior was measured by differential
      scanning calorimetry and quartz crystal microbalance (QCM). Addition of polymyxin
      B of up to 0.5 mg/mL to the 5.0 mg/mL LPS solution increased gel-to-liquid
      crystalline phase transition enthalpy (delta H) and raised the transition
      temperature (tmax). The further addition of polymyxin B reduced the delta H
      value. Gramicidin S produced a different effect, whereby a minor addition reduced
      tmax and delta H value of the LPS. The LPS film on the platinum electrode of the
      QCM indicated a downward shift of resonant frequency and an upward shift of
      resonant resistance when in contact with the antibiotic solution. An
      interpretation of these variations is that the LPS on the QCM electrode changed
      not only film weight, but also viscoelasticity owing to contact with the
      antibiotic solution. The different effects between the antibiotics between
      polymyxin B and gramicidin S on the LPS are induced by the difference of the
      governing effect. Polymyxin B interacts with the LPS electrostatically, whereas
      gramicidin S interacts by hydrophobic moieties.

PMID- 7528000
TI  - [Participation and nursing care in ablation procedures with radiofrequency in
      supraventricular tachycardia].

PMID- 7527999
TI  - Analogues of peptide 9-21 of glycoprotein D of herpes simplex virus and their
      binding to group VII monoclonal antibodies.
AB  - Several analogues of the amino acid sequence of peptide 9-21 of glycoprotein D of
      herpes simplex virus type 1 (HSV-1) were synthesized and investigated for
      reactivity with different group VII monoclonal antibodies, Mabs LP14, ID3, 170,
      HD4, A16, EII-24 and Ev-10, in a competition enzyme-linked immunosorbent assay
      (ELISA). Replacement of Arg at position 16 by His resulted in a loss of binding
      with the group VII Mabs. Substitution of Pro at residue 14 by Leu gave a reduced
      binding for a number of Mabs and loss of binding for Mab A16. Substitution of Lys
      at position 10 by Glu gave reduced binding for three out of the seven Mabs. In
      addition substitutions of Met at position 11 by norleucine and oxidized Met were
      studied. The boundaries of the epitope cluster were mapped by studying synthetic
      variants of peptide 9-21 which were shorter either at the C-terminus or at the N
      terminus, or both. Peptide 10-18 and peptide 9-17 were the shortest peptides,
      which were still reactive with the group VII Mabs. Mab HD4 requires the N
      terminus of peptide 9-21 for effective binding, while for binding of other Mabs
      contribution of the residues in the C-terminal part of this peptide is more
      important.

PMID- 7528002
TI  - Specific motifs in T cell receptor V beta D beta J beta gene sequences in
      multiple sclerosis lesions in brain.

PMID- 7528001
TI  - Glucagonoma syndrome with increased lactate dehydrogenase isoenzymes: octreotide
      treatment.
AB  - Glucagonoma Syndrome is a rare syndrome comprising hyperglucagonemia, diabetes
      mellitus, necrolytic migratory erythema and hypoaminoacidemia in the setting of a
      glucagon producing, alpha cell tumour of the pancreas. We report a case of
      Glucagonoma Syndrome palliatively treated successfully with octreotide. In
      addition to classical clinical and biochemical findings, this patient also had a
      Glomus Jugulare tumour, and Empty Sella Syndrome and demonstrated an unusual
      pattern of plasma lactate dehydrogenase isoenzymes, features not previously
      reported in this syndrome.

PMID- 7527998
TI  - Induction of interferon by virus glycoprotein(s) in lymphoid cells through
      interaction with the cellular receptors via lectin-like action: an alternative
      interferon induction mechanism.
AB  - When animals and cells are infected with a virus, interferon is produced. Viral
      nucleic acid is considered to be one of actual components for interferon
      induction. In addition, viral glycoproteins trigger interferon induction in
      lymphoid cells by membrane-membrane interaction via a lectin-like activity. A
      biological significance of lectin-like activity of viral glycoproteins is
      discussed.

PMID- 7528003
TI  - T cell epitopes in human papilloma virus proteins.
AB  - Infection by HPV is associated with several human diseases such as warts of the
      skin, condylomata of the genital track and carcinoma of the cervix. Although
      there is strong evidence for immune control of HPV types causing warts and
      condylomata, it is currently unclear whether patients infected with transforming
      HPV types can mount efficient T cell responses. Despite the apparent low
      immunogenicity of transforming HPV types, several Th and CTL epitopes have been
      identified in proteins derived from HPV16. This transforming virus is most
      frequently present in women with CIN and cervical carcinoma and knowledge of T
      cell recognisable proteins may eventually lead to the design of immune
      stimulating anti-HPV16 vaccines.

PMID- 7528005
TI  - Synthesis and characterization of 3H-labelled tetrahydrobiopterin.
AB  - We synthesized [3'-3H]-5,6,7,8-tetrahydrobiopterin from [8,5'-3H]guanosine 5'
      triphosphate ([8,5'-3H]GTP) using GTP cyclohydrolase (EC 3.5.4.16), 6
      pyruvoyltetrahydropterin synthase and sepiapterin reductase (EC 1.1.1.153). After
      purification by cation-exchange h.p.l.c. a solution of radiochemically pure (>
      95%) [3'-3H]-5,6,7,8-tetrahydrobiopterin with a specific activity of 9.2 Ci/mmol
      was obtained. The product proved well suited for studying the binding of
      tetrahydrobiopterin to nitric-oxide synthase.

PMID- 7528006
TI  - Nitric oxide production is intensely and persistently increased in tissue by
      thermal injury.
AB  - NO is a major messenger molecule which regulates immunity and vascular tone,
      serves as a neurotransmitter and participates in wound healing. It has also been
      known to be increased in vivo by thermal injury. Urinary nitrate excretion and
      tissue levels of NO synthase activity were measured after a non-lethal thermal
      injury. Urinary nitrate excretion decreased by 90% 24-48 h after injury, but
      dramatically increased by 10-fold thereafter for 30-40 days after injury and
      remained elevated until the wound healed. This response was inhibited by a
      competitive inhibitor of NO synthase. These rates of urinary nitrate excretion
      suggest that NO production is dramatically affected by injury in a pattern that
      is distinct from that observed after lipopolysaccharide administration. On the
      basis of these findings, we suggest that the hyperdynamic cardiovascular and
      hypermetabolic responses seen to continue weeks after thermal injury could be a
      result of the autocrine and paracrine effects of NO generated locally within the
      tissues in addition to that generated by inflammatory cells.

PMID- 7528009
TI  - Purification, characterization and analysis of rolipram inhibition of a human
      type-IVA cyclic AMP-specific phosphodiesterase expressed in yeast.
AB  - Analyses were done on a human type-IV cyclic AMP (cAMP) phosphodiesterase (hPDE
      IVA-h6.1) expressed in an engineered strain of Saccharomyces cerevisiae. This
      strain (YMS6) expressed soluble PDE activity, together with an insoluble activity
      which was not released by re-homogenization, treatment with high-ionic-strength
      solutions or with the detergent Triton X-100. Pellet and soluble PDE activities
      were typical of type-IV PDE. They were cAMP-specific, insensitive to the addition
      of either cGMP (1 microM) or Ca2+/calmodulin, and inhibited by rolipram.
      Thermostability studies showed both activities to decay as single exponentials,
      indicating the presence of homogeneous PDE protein species in each fraction.
      Pellet PDE activity was more thermostable than the soluble enzyme. Mg2+ and Mn2+
      dose-dependently increased PDE activity and reversed the inactivating effect of
      EDTA.h6.1 was engineered to express a C-terminal five-histidine motif (h6.1his5).
      This allowed purification of the PDE to apparent homogeneity in a simple two-step
      process involving a rolipram affinity column and a Ni2(+)-chelate column. A
      single monomeric protein of subunit molecular mass approximately 73 kDa and
      native molecular mass approximately 74 kDa resulted after a approximately 53000
      fold purification. This exhibited a Km for cAMP of 8 microM, a true Vmax. of 0.8
      mumol of cAMP hydrolysed/min per mg of PDE protein, a kcat. of 3702 s-1, and a
      value of the specificity constant kcat/Km of 4.6 x 10(8) M-1.s-1, the last
      implying a diffusion controlled reaction. Rolipram (Ki 0.4 soluble; 0.7 microM
      pellet) and 3-isobutyl-1-methylxanthine (Ki 15 soluble; 19 microM pellet) served
      as simple competitive inhibitors for both soluble and pellet forms of h6.1,
      respectively.

PMID- 7528004
TI  - Pteridine biosynthesis and nitric oxide synthase in Physarum polycephalum.
AB  - Physarum polycephalum, an acellular slime mould, serves as a model system to
      study cell-cycle-dependent events since nuclear division is naturally
      synchronous. This organism was shown to release isoxanthopterin which is
      structurally related to tetrahydrobiopterin, a cofactor of aromatic amino acid
      hydroxylases and of nitric oxide synthases (NOSs) (EC 1.14.13.39). Here, we
      studied Physarum pteridine biosynthesis in more detail and found that high
      amounts of tetrahydrobiopterin are produced and NOS activity is expressed.
      Physarum pteridine biosynthesis is peculiar in as much as 7,8-dihydroneopterin
      aldolase (EC 4.1.2.25), an enzyme of folic acid biosynthesis usually not found in
      organisms producing tetrahydrobiopterin, is detected in parallel. NOS purified
      from Physarum depends on NADPH, tetrahydrobiopterin and flavins. Enzyme activity
      is independent of exogenous Ca2+ and is inhibited by arginine analogues. The
      purified enzyme (with a molecular mass of 130 kDa) contains tightly bound
      tetrahydrobiopterin and flavins. During the synchronous cell cycle of Physarum,
      pteridine biosynthesis increases during S-phase whereas NOS activity peaks during
      mitosis, drops at telophase and peaks again during early S-phase. Our results
      characterize Physarum pteridine biosynthesis and NOS and suggest a possible link
      between NOS activity and mitosis.

PMID- 7528007
TI  - Dexamethasone differentially affects interleukin 1 beta- and cyclic AMP-induced
      nitric oxide synthase mRNA expression in renal mesangial cells.
AB  - Inducible nitric oxide synthase (iNOS) is expressed in renal mesangial cells in
      response to two principal classes of activating signals that interact in a
      synergistic fashion. These two groups of activators comprise inflammatory
      cytokines such as interleukin (IL)-1 beta or tumour necrosis factor alpha and
      agents that elevate cellular levels of cyclic AMP (cAMP). We examined whether
      dexamethasone differentially affects iNOS induction in response to IL-1 beta and
      a membrane-permeable cAMP analogue, N6,O-2'-dibutyryladenosine 3',5'-phosphate
      (Bt2cAMP). Nanomolar concentrations of dexamethasone suppress IL-1 beta- as well
      as Bt2cAMP-induced iNOS protein expression and production of nitrite, the stable
      end product of nitric oxide (NO) formation. In contrast, dexamethasone prevents
      induction of iNOS mRNA in response to Bt2cAMP without affecting IL-1 beta
      triggered increase in iNOS mRNA levels. These data suggest that dexamethasone
      acts at different levels, depending on the stimulus used to suppress iNOS
      induction in mesangial cells.

PMID- 7528008
TI  - Modulation of Ca(2+)-stimulated glutamate release from synaptosomes by Na+ entry
      through tetrodotoxin-sensitive channels.
AB  - Tityustoxin (TsTX), a toxin obtained from the venom of the Brazilian scorpion
      Tityus serrulatus, stimulates Na+ influx through tetrodotoxin (TTX)-sensitive Na+
      channels which, in turn, promotes both Ca(2+)-dependent and Ca(2+)-independent
      release of glutamate from rat cerebrocortical synaptosomes. The level of Ca(2+)
      dependent glutamate release after addition of 0.5 microM TsTX is greater than
      that produced by a maximally depolarizing concentration of KCl. This effect of
      TsTX, which is entirely dependent on Na+ entry, suggests that Na+ has a role in
      modulating Ca2+ entry and glutamate release that is not simply related to
      membrane depolarization. In order to investigate possible modulatory role(s) of
      Na+ on Ca(2+)-dependent glutamate release, we compared the effects of TsTX with
      those of KCl and the Na+ ionophore gramicidin D. When used alone, 100 nM
      gramicidin D produced a larger increase in intrasynaptosomal free Na+ than did
      0.5 microM TsTX, and a similar rise in intrasynaptosomal free Ca2+, but was much
      less effective in promoting glutamate release. Even the combination of membrane
      depolarization (by 33 mM KCl) and elevation of intrasynaptosomal free Na+ (by 100
      nM gramicidin) was still less effective than TsTX at causing Ca(2+)-dependent
      glutamate release. These data suggest that localized Na+ entry, through TTX
      sensitive Na+ channels, exerts a modulatory role on Ca(2+)-dependent glutamate
      release from nerve endings in the cerebral cortex.

PMID- 7528010
TI  - Inhibition by somatostatin of amylase secretion induced by calcium and cyclic AMP
      in rat pancreatic acini.
AB  - It has recently been shown that somatostatin inhibits amylase secretion from
      isolated pancreatic acini by reducing cyclic AMP (cAMP) production [Matsushita,
      Okabayashi, Hasegawa, Koide, Kido, Okutani, Sugimoto and Kasuga (1993)
      Gastroenterology 104, 1146-1152]. To date, however, little is known as to the
      other mechanism(s) by which somatostatin inhibits amylase secretion in exocrine
      pancreas. To investigate the action of somatostatin independent of cAMP
      generation, we examined the effect of somatostatin in isolated rat pancreatic
      acini stimulated by 1 microM calcium ionophore A23187 and 1 mM 8-bromo-cyclic AMP
      (8Br-cAMP). Somatostatin inhibited amylase secretion evoked by a combination of
      A23187 and 8Br-cAMP in a dose-dependent manner. The maximum inhibition was
      obtained by 10(-7) M somatostatin, and at this concentration somatostatin
      inhibited the effect of A23187 and 8Br-cAMP by approximately 30%. In electrically
      permeabilized acini, an elevation of free calcium concentration resulted in an
      increase in amylase secretion and cAMP enhanced the secretion evoked by calcium.
      cAMP shifted the dose-response curve for calcium-induced secretion leftwards and
      elevated the peak value of secretion. Somatostatin inhibited the effect of cAMP
      on calcium-induced amylase secretion by shifting the dose-response curve to the
      right. To determine the involvement of a G-protein(s), we examined the effect of
      somatostatin in acini pretreated with pertussis toxin. Pretreatment of acini with
      pertussis toxin completely blocked somatostatin-inhibition of amylase-secretion
      evoked by A23187 and 8Br-cAMP. These results indicate that somatostatin decreases
      amylase secretion induced by cAMP and calcium by reducing the calcium sensitivity
      of exocytosis. A pertussis toxin-sensitive G-protein is also involved in this
      step.

PMID- 7528012
TI  - Molecular cloning of the rat analogue of human CD59: structural comparison with
      human CD59 and identification of a putative active site.
AB  - We have previously described the purification and partial characterization of the
      rat analogue of the human complement regulatory molecule CD59 [Hughes,
      Piddlesden, Williams, Harrison and Morgan (1992) Biochem. J. 284, 169-176]. We
      present here the molecular cloning and full sequence analysis of this molecule. A
      PCR-based approach utilizing primers designed from the amino-terminal protein
      sequence was used to isolate a full-length cDNA clone from a rat kidney cDNA
      library. This clone encoded a 92 bp 5'-flanking sequence, a 66 bp signal peptide
      and a 315 bp coding region containing putative glycosylation and GPI-anchor
      signals. The 3' untranslated flanking region was approximately 1.1 kbp long and
      included the poly-A tail and a CATA repeating sequence. The coding region was 58%
      identical with the human cDNA at the nucleotide level and 44% identical at the
      amino acid level. Despite this relatively low overall sequence conservation,
      several highly conserved stretches were apparent, particularly in the N-terminal
      portion of the molecule, in the cysteine-rich region immediately preceding the
      site of glycolipid attachment and in the C-terminal peptide removed during
      glycolipid attachment. An N-glycosylation site was identified at Asn-16 and a
      putative glycosylphosphatidylinositol anchor addition site at Asn-79, indicating
      that the mature processed protein was two residues longer than human CD59.
      Comparison of the sequences of rat and human CD59, together with consideration of
      the published three-dimensional structure of human CD59 and functional data,
      implicates specific regions of the protein in interactions with C-8 and/or C-9.

PMID- 7528011
TI  - The vitronectin receptor (alpha v beta 3) is implicated, in cooperation with P
      selectin and platelet-activating factor, in the adhesion of monocytes to
      activated endothelial cells.
AB  - In this study we have investigated the presence on endothelial cells of potential
      glycoprotein receptors, other than P-selectin, which are involved in the adhesion
      of monocytes at the early stages of activation. We report that the majority of
      cells binding to thrombin-activated endothelial cells from a peripheral blood
      mononuclear cell (PBMC) preparation are monocytes. The adhesion of PBMC to
      thrombin-activated, but not resting, endothelial cells was inhibited (66%) by a
      monoclonal antibody (mAb) directed against alpha v beta 3. Elutriated monocytes
      or a monocytic cell line (U937) were also inhibited by this antibody, its F(ab)'2
      fragments and three other anti-(alpha v beta 3) mAbs. alpha v beta 3 isolated
      from endothelial-cell lysates significantly inhibited the adhesion of monocytes
      and U937 cells to endothelial cells. A peptide motif (RGDF) known to interact
      with alpha v beta 3 inhibited U937 cell adhesion to activated endothelial cells
      by 53%. Finally, an anti-(P-selectin) mAb (LYP20) or a platelet-activating factor
      (PAF)-receptor antagonist (WEB 2086) inhibited monocyte adhesion to activated
      endothelial cells. This study shows for the first time that alpha v beta 3 is
      implicated, in addition to P-selectin and PAF, in the adhesion of monocytes to
      activated endothelial cells.

PMID- 7528013
TI  - CFTR does not alter acidification of L cell endosomes.
AB  - Endosomes from L cells, transduced with the CFTR gene, and the parental line,
      which does not express detectable levels of CFTR, were loaded with FITC-dextran,
      isolated and the initial rates of acidification, steady-state pHi, and proton
      leak rates were compared over a range of chloride concentrations (0-140 mM).
      Values for these parameters were similar for endosomes from both cell lines in
      the presence and absence of cAMP and PKA. These results indicate that CFTR does
      not alter L cell endosome acidification, possibly due to an adequate intrinsic CI
      conductance or to a failure to incorporate sufficient functional CFTR or a
      necessary co-factor in endocytic membranes.

PMID- 7528015
TI  - Nitric oxide synthase activity is elevated in brain microvessels in Alzheimer's
      disease.
AB  - The cerebral microcirculation undergoes specific biochemical changes in
      Alzheimer's disease. In this study, we have compared the nitric oxide synthase
      (NOS) activity of brain microvessels isolated from Alzheimer and control brains.
      L-[3H]-citrulline, the stable co-product generated with nitric oxide (NO) from L
      [3H]-arginine, was measured as an indicator of NOS activity. The results
      indicated a significant increase in NOS activity in microvessels isolated from
      Alzheimer brains. In addition, using antibodies to both the endothelial and
      inducible NOS isoforms, we demonstrated a significant increase in enzyme level in
      Alzheimer-derived vessels. Elevated vascular production of NO, a potentially
      neurotoxic mediator in the CNS, may contribute to the susceptibility of neurons
      to injury and cell death in Alzheimer's disease.

PMID- 7528014
TI  - Cytochrome P4502A5 expression and inducibility by phenobarbital is modulated by
      cAMP in mouse primary hepatocytes.
AB  - Factors involved in CYP2A5 expression were studied in mouse liver primary
      hepatocytes in culture. CYP2A5-mediated coumarin 7-hydroxylase (COH) activity was
      retained in simple culture conditions for at least 96 hours and the activity was
      inducible up to 33-fold by phenobarbital (PB). The constitutive activity and
      inducibility of COH was totally blocked by treatment of hepatocytes with
      actinomycin D, and short initial treatment with cycloheximide caused
      superinducibility when co-administered with PB. Treatment of hepatocytes with
      inhibitors of protein kinase C, tyrosine kinases and a generator of nitric oxide
      did not affect COH basal activity or inducibility. Administration of dibutyryl
      cAMP, forskolin, and 3-isobutyl-1-methylxanthine (IBMX) enhanced both basal and
      PB-induced COH activities and CYP2A5 mRNA levels, indicating that cAMP plays a
      major role in CYP2A5 expression.

PMID- 7528016
TI  - cis-acting elements in 5'-flanking region of rat alpha-fetoprotein mediating
      retinoic acid responsiveness.
AB  - A distal RA responsive cis-acting element has been identified in the 5'-flanking
      region of the alpha-fetoprotein gene by transfection of different deletion
      mutants of AFP-CAT fusion gene. The retinoic acid receptor specifically binds to
      this RA responsive cis-acting element in mobility shift assays. Furthermore, this
      cis-acting element functions in exogenous TK promoter in transient cotransfection
      assays. This study suggests a role for the RA responsive cis-acting element in
      the RA induction of alpha-fetoprotein gene expression.

PMID- 7528017
TI  - Human retina expresses both constitutive and inducible isoforms of nitric oxide
      synthase mRNA.
AB  - The present study provided evidence for the presence of two forms of nitric oxide
      synthase(NOS) gene in the human retina. Expression of retinal constitutive
      type(rbNOS) and inducible type(riNOS) of NOS was detected in human retinal poly
      A+RNA by reverse transcriptase polymerase chain reaction (RT-PCR) method. The
      deduced amino acid sequence of the human retinal rbNOS showed more than 99%
      homology with human brain bNOS and that of riNOS was identical to the
      chondrocytes inducible iNOS with the exception for one amino acid. These
      differences in amino acid sequences of rbNOS and riNOS, with their counterparts
      in human brain and human chondrocytes sequences, were only in the non-cofactor
      binding sites. Northern blot analysis of the human retinal poly A+RNA and total
      RNA, using the PCR-amplified riNOS probe revealed the existence of riNOS message
      with the appearance of the band with the expected size of 4.4kb, while the
      message for rbNOS was not detectable. This was the first report of the deduced
      nucleotide sequence identification of two NOS genes from a human tissue, while
      there had been earlier reports from culture cells.

PMID- 7528018
TI  - Increased expression of endothelial constitutive nitric oxide synthase in rat
      aorta during pregnancy.
AB  - The mechanisms underlying enhanced vascular reactivity in pregnancy are not yet
      defined. In this study we have investigated the potential role of endothelium
      derived vasodilator nitric oxide (EDNO). EDNO-mediated dilatory responses in
      vitro were markedly increased in aorta of pregnant as compared with nonpregnant
      rats. This increase in EDNO-releasability was accompanied by a two-fold increase
      in mRNA of endothelial constitutive nitric oxide synthase (NOS-III). Chronically
      substituted estrogen, but neither progesterone nor testosterone induced an
      upregulation of NOS-III mRNA in aorta of gonadectomized rats which amounted to
      about half that induced in aorta of pregnant rats. Thus, increased EDNO
      releasability and increased NOS-III mRNA contribute to enhanced vascular
      reactivity in pregnancy.

PMID- 7528019
TI  - Glycosaminoglycan binding characteristics of the insulin-like growth factor
      binding proteins.
AB  - Interactions between the IGF-binding proteins (IGFBPs) and glycosaminoglycans
      (GAGs) such as heparin may be involved in the regulatory control of IGF exerted
      by the IGFBPs at the level of the extracellular matrix and capillary endothelium,
      although the precise mechanisms of this remain uncertain. We have searched
      primary sequences of human, rat and bovine IGFBPs-1 to -6 for putative GAG
      binding consensus sequences (XBBXBX and XBBBXXBX, where B represents any basic
      amino acid and X is undefined). At least one such sequence was identified in each
      IGFBP examined except human and rat IGFBP-4 and rat IGFBP-6, with IGFBP-5
      containing three GAG-binding consensus sequences. Additionally, the bovine IGF
      type II receptor was found to contain two such sequences in the intracellular
      region. Affinity of the IGFBP preparations for heparin was examined
      experimentally by affinity chromatography using pooled fractions of fetal and
      adult ovine plasma obtained by size exclusion chromatography. Pooled fractions of
      150 kDa (containing IGFBP-3 alone by IGF ligand blot analysis) and 40-50 kDa
      (containing IGFBPs-3 and -2, together with proteins of 29, 24 and 25-28 kDa which
      may include IGFBP-4 and IGFBPs-1, -5 and -6) were found to bind strongly to the
      matrix necessitating high salt concentrations for their elution; however, in
      contrast, a > 200 kDa fraction containing the soluble form of the type II
      receptor failed to bind. Recombinant human non-glycosylated IGFBP-3 also bound
      strongly to the affinity adsorbent. No evidence of dissociation of bound IGF from
      binding protein complexes by association with the matrix was obtained from this
      experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528020
TI  - The ontogeny of insulin-like growth factor (IGF) and IGF-binding protein gene
      expression in the rat pancreas.
AB  - Insulin is important for optimal fetal and neonatal growth and development. Its
      continued availability is due, in part, to ongoing islet cell growth within the
      pancreas. IGFs and IGF-binding proteins (IGFBPs) have been implicated as
      paracrine regulators of islet cell growth within the developing pancreas. The
      purpose of this study was to determine whether the intact rat pancreas expresses
      mRNAs for IGF-I, IGF-II and IGFBPs, and how these might change with development.
      Liver was studied as a control tissue. Pancreas and liver were taken from fetal
      rats at 20-22 days of gestation, from postnatal rats at 1-21 days and from adult
      animals, and mRNAs for IGFs-I and -II and IGFBPs-1 to -6 were detected by
      Northern blot hybridization. The amount of IGF-II mRNA was greatest in the liver
      and pancreas of the fetal rat, and declined in both tissues during the neonatal
      period. Conversely, IGF-I mRNA levels were low but detectable in fetal life, and
      rose to adult levels within 2 weeks of birth. Both IGFBP-1 and IGFBP-2 mRNAs were
      present in fetal rat liver, increasing in amount over the first week of life, and
      declining in the adult. However, within the pancreas, IGFBP-1 mRNA was
      undetectable and IGFBP-2 mRNA was very low in the fetus and neonate. Both IGFBP-1
      and IGFBP-2 mRNAs transiently appeared in the pancreas between postnatal weeks 2
      and 3 and declined in the adult. IGFBP-3 and IGFBP-4 mRNAs were detected in both
      the liver and pancreas throughout the developmental period studied. IGFBP-3 mRNA
      increased in amount immediately following birth, while the quantity of IGFBP-4
      mRNA increased sharply in liver from postnatal day 21, but declined in the
      pancreas. mRNA for IGFBP-5 or -6 was undetectable in either tissue. The reslts
      show that both IGF-I and IGF-II are expressed by rat pancreas from at least 20
      days of gestation, the latter being predominant in fetal life and the former
      during postnatal development. In addition, at least four IGFBP mRNAs (IGFBPs-1, 
      2, -3 and -4) were expressed within the pancreas with distinct developmental
      patterns. IGFBP-3 and -4 were predominant in the fetal and neonatal periods,
      while increased expression of IGFBPs-1 and -2 occurred 2-3 weeks after birth. The
      ontogeny of IGFBP mRNA expression in pancreas differed from that in
      liver.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7528023
TI  - Topical capsaicin-pharmacology and potential role in the treatment of
      temporomandibular pain.
AB  - Capsaicin is an over-the-counter topical analgesic marketed at 0.025% and 0.075%
      concentrations. It is currently approved by the United States Food and Drug
      Administration for the topical relief of pain due to rheumatoid arthritis,
      osteoarthritis and various neuralgias. This paper will review the basic and
      clinical pharmacology of capsaicin, and discuss its potential role in the
      management of pain in the temporomandibular joint region.

PMID- 7528021
TI  - Effects of oestrogen on rat uterine expression of insulin-like growth factor
      binding proteins.
AB  - Previous studies have established that the IGFs are involved in oestrogen-induced
      uterine proliferation. IGF-binding proteins (IGFBPs) are present in most
      biological fluids and tissues and may modulate the actions of the IGFs. We
      examined uterine, hepatic and renal expression of the IGFBPs throughout the
      oestrous cycle and investigated the effects of oestradiol (OE2) on IGFBP
      expression in ovariectomized (ovx) rats. Uterine expression of IGFBPs-1 and -3
      showed a definite variation throughout the oestrous cycle with highest levels
      during dioestrus. In the liver and kidney the changes in IGFBP-1 and IGFBP-3 mRNA
      abundance were the opposite of those observed in the uterus, with the highest
      levels observed during oestrus. Administration of OE2 to ovx rats decreased
      uterine IGFBP-3 mRNA and increased IGFBP-4 mRNA levels. In these rats there were
      no consistent changes in renal IGFBP-1 or IGFBP-3 mRNAs; however, a significant
      increase in IGFBP-4 mRNA was observed in this tissue, as in the uterus. In the
      liver an increase in IGFBP-1 mRNA and a decrease in IGFBP-3 mRNA levels were
      observed in rats treated with OE2. Despite changes in uterine, hepatic and renal
      IGFBP mRNA levels, no significant variation was seen in serum IGFBPs as
      determined by ligand blotting of sera. These data demonstrate that there is a
      cyclical variation in the expression of the IGFBPs in the uterus, kidney and
      liver, and that OE2 is able to modulate differentially IGFBP expression in these
      tissues.

PMID- 7528022
TI  - Reduced expression of phospholipase C-delta, a signal-transducing enzyme, in rat
      colon neoplasms induced by methylazoxymethanol acetate.
AB  - Phospholipase C (PLC), which hydrolyzes phosphoinositides, has been implicated as
      a key enzyme in signal transduction. We examined the expression of an isozyme of
      PLC, PLC-delta, in rat colon neoplasms induced by methylazoxymethanol (MAM)
      acetate. Large-bowel neoplasms were observed in five of 10 rats given MAM acetate
      (25 mg/kg body weight, by interperitoneal injection at 6 and 7 wk of age) 40 wk
      after treatment. Expression of PLC-delta in the neoplasms was not detected by
      northern blot analysis, and a low level of expression was detected by immunoblot
      analysis, although PLC-delta expression was apparent in the non-neoplastic colon
      mucosae of MAM acetate-treated rats as well as in the colon mucosae of control
      rats. Furthermore, analysis by reverse transcriptase-polymerase chain reaction
      revealed that the ratio of the expression of PLC-delta to that of beta-actin in
      the neoplasms was significantly lower than the ratios in the non-neoplastic colon
      mucosae of carcinogen-treated and control rats (P < 0.01). However, the ornithine
      decarboxylase (ODC) activity in the neoplasms was significantly greater than that
      of the non-neoplastic and control mucosae (P < 0.001). The differences in the
      levels of PLC-delta expression in neoplastic and non-neoplastic tissues and the
      inverse correlation of PLC-delta expression with ODC activity may suggest that
      PLC-delta has little effect on the PLC-mediated mitogenic signaling system, at
      least in MAM acetate-induced colon neoplasms in rats.

PMID- 7528024
TI  - Substance P decreases extracellular concentrations of acetylcholine in
      neostriatum and nucleus accumbens in vivo: possible relevance for the central
      processing of reward and aversion.
AB  - It has been shown that peripherally administered substance P has reinforcing
      effects and can promote functional recovery after unilateral partial lesion of
      the nigrostriatal system. Furthermore, peripheral injection of substance P
      induces an increase in extracellular striatal dopamine. To obtain further
      information about the central mechanisms of these properties we used the in vivo
      microdialysis technique to investigate changes in the extracellular
      concentrations of acetylcholine in neostriatum and nucleus accumbens after
      intraperitoneal (i.p.) administration of substance P or vehicle in freely moving
      rats. The i.p. administration of 50 micrograms/kg substance P induced a steady,
      long-lasting decrease in the extracellular concentrations of acetylcholine in
      neostriatum, while no changes were observed in the nucleus accumbens. In
      comparison, substance P in a dose of 250 micrograms/kg i.p. acutely decreased the
      extracellular levels of acetylcholine in both nuclei. Interestingly, after the
      administration of vehicle, an acute increase in acetylcholine levels was observed
      in the nucleus accumbens, but not in the neostriatum. This effect did not occur
      after the injection of substance P indicating that the neurokinin blocked the
      increase in acetylcholine levels induced by the vehicle injection. These effects
      of substance P on striatal acetylcholine are discussed with respect to their
      relationship with dopamine and endogenous opiates, and with respect to the
      functional role of substance P, such as in reward, aversion, motor activity, and
      functional recovery.

PMID- 7528025
TI  - Control of cardiac gene transcription by fibroblast growth factors.
AB  - Skeletal alpha-actin (SkA) is representative of the cardiac genes that are
      expressed at high levels in embryonic myocardium, downregulated after birth, and
      reactivated by tropic signals including basic fibroblast growth factor (FGF-2)
      and type beta transforming growth factors (TGF beta). To investigate the
      molecular basis for cardiac-restricted and growth factor-induced SkA
      transcription, we have undertaken a mutational analysis of the SkA promoter in
      neonatal ventricular myocytes, with emphasis on the role of three nominal serum
      response elements. Serum response factor (SRF) and the bifunctional factor YY1
      are the predominant cardiac proteins contacting the proximal SRE (SRE1).
      Mutations of SRE1 that prevent recognition by SRF and YY1. or SRF alone,
      virtually abolish SkA transcription; mutation of distal SREs was ineffective. A
      mutation which selectively abrogates YY1 binding increases expression,
      substantiating the predicted role of YY1 as an inhibitor of SRF effects. SkA
      transcription requires combinational action of SRE1 with consensus sites for Sp1
      and the SV40 enhancer binding protein, TEF-1. As an isolated motif, SRE1 can
      confer responsiveness to both FGF-2 and TGF beta to a heterologous promoter.
      Whether TEF-1 binding sites likewise can function as FGF response elements is
      unknown. Molecular dissection of mechanisms that govern the differentiated
      cardiac phenotype has largely been undertaken to date in neonatal ventricular
      myocytes, as the adult ventricular myocyte has been refractory to conventional
      procedures for gene transfer. To circumvent expected limitations of other
      methods, we have used replication-deficient adenovirus to achieve efficient gene
      transfer to adult cardiac cells in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528026
TI  - Potential mechanisms regulating the extracellular activities of basic fibroblast
      growth factor (FGF-2).
AB  - Basic fibroblast growth factor (FGF-2) is nearly ubiquitous in its distribution,
      leading numerous investigators to propose that there must exist highly specific
      mechanisms to regulate its bioavailability. Moreover, in each of the tissues
      where it can be localized, numerous cells are its potential target. The
      identification of these mechanisms could serve as an important step in developing
      novel strategies to inhibit FGF action. It could be possible to block such FGF
      dependent activities as angiogenesis, tumor growth, reproduction, and selected
      diseases of cell proliferation. Over the course of the past several years, we
      have attempted to describe some of the processes that might regulate a target
      cell's ability to activate FGF-2 in its local milieu.

PMID- 7528027
TI  - FGFs and their receptors, in vitro and in vivo studies: new FGF receptor in the
      brain, FGF-1 in muscle, and the use of functional analogues of low-affinity
      heparin-binding growth factor receptors in tissue repair.
AB  - Several heparin-binding growth factors (HBGFs) are thought to play a key role in
      the natural processes of tissue homeostasis, regeneration or repair. The HBGFs
      are active upon release from neighbouring inflammatory or circulating cells, as
      well as upon release from heparan sulfate proteoglycosaminoglycans that are
      associated with the extracellular matrix (ECM). To better understand the
      physiological role of these HBGFs, we have focused our effort on studying a
      subset of HBGFs, namely FGF-1 and FGF-2 and their receptors. We present the
      purification and characterisation of a new form of heparin-binding FGF receptor
      from adult bovine brain (Perderiset et al., 1992). This receptor has now been
      purified to homogeneity. Ligand blot and cross-linking experiments performed with
      labeled FGF-1 or FGF-2 revealed 80-kd and 130-kd bands. Preliminary sequence
      information indicates that receptor is different from the receptors, FGFR-1 to 
      4, but it may be related the cysteine-rich-FGF receptor (CFR). We have previously
      shown that FGF-1, but not FGF-2, is specifically expressed in myoblastic
      satellite cells during the proliferating phase preceding myoblast alignment and
      fusion. We have now transfected primary cultures of rat myoblastic satellite
      cells with FGF-1 cDNA and expressed this growth factor constitutively. The
      transfected cells were no longer able to form myotubes. Transfection with
      antisense FGF-1 induced myotube formation suggesting that endogenous expression
      of FGF-1 is associated with myoblastic cell differentiation. Numerous studies
      have concluded that the ECM represents a natural reservoir for various
      HBGFs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528029
TI  - Long-term results of two VAB-like regimens (vinblastine + actinomycin-D +
      bleomycin + cyclophosphamide + cisplatin) in malignant germ cell tumours of the
      ovary.
AB  - 21 patients with malignant germ cell tumours of the ovary were treated with two
      chemotherapy regimens including vinblastine, actinomycin-D, bleomycin,
      cyclophosphamide and cisplatin. Chemotherapy was delivered as primary
      postoperative therapy in 15 patients and for recurrent disease in 6 patients. 3
      of 4 patients with pure dysgerminomas and 10 of 17 patients with non
      dysgerminomatous tumours are alive without evidence of disease. The overall
      progression-free survival is 62% (95% confidence interval 45-77) with a median
      follow-up of 7 years. Two toxic deaths were observed. Less toxicity and better
      efficacy favour etoposide- and cisplatin-based regimens as standard chemotherapy
      for germ cell tumours of the ovary.

PMID- 7528028
TI  - Structure-function studies of FGF-1: dissociation and partial reconstitution of
      certain of its biological activities.
AB  - We reported previously that the mitogenic activities of FGF-1 (acidic FGF) could
      be dissociated from its receptor-binding activities by site-directed mutagenesis
      of lysine 132 to a glutamic acid. Although the mutant FGF-1 protein binds to the
      high-affinity tyrosine-kinase receptors, stimulates tyrosine-kinase activity, and
      promotes expression of immediate-early genes, it is not mitogenic for a variety
      of tested cell lines. Interestingly, the mutant FGF-1 is capable of other
      functions associated with the wild-type protein such as promotion of mesoderm
      formation in Xenopus animal caps. The mutant exhibits a reduced apparent affinity
      for heparin-Sepharose compared to the wild-type protein. The relationship between
      the reduced heparin affinity and lack of mitogenic activity of this mutant is not
      clear. Recent data indicates the relationship is not as simple as reduced
      stability of the protein. When NIH 3T3 cells are transfected with expression
      vectors encoding either wild-type or mutant FGF-1, a transformed phenotype can be
      seen in cells overexpressing the wild-type FGF-1, whereas cells overexpressing
      mutant FGF-1 appear normal. Analysis of lysates of these cells indicates that a
      tyrosine-kinase cascade, distinct from that associated with the high-affinity
      cell surface receptors, has been activated in the wild-type transfected cells but
      not in the mutant transfected cells. Although both transfected cell lines contain
      FGF-1 cell surface receptors as judged by crosslinking studies, the wild-type
      transfectants are refractory to exogenous FGF-1, whereas the mutant transfectants
      respond normally.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528030
TI  - Treatment of unresectable hepatocellular carcinoma with a combination of human
      recombinant alpha-2b interferon and doxorubicin: results of a pilot study.
AB  - Based on the in vitro and in vivo potentiation of the cytotoxic activity of
      chemotherapeutic agents by the interferons, a pilot study combining human
      recombinant alpha-2b interferon (IFN) and doxorubicin was conducted for the
      treatment of unresectable, histologically proven hepatocellular carcinoma.
      Between March 1988 and May 1990, 21 patients (median age: 60 years, range: 29-76)
      entered the study. The dose of doxorubicin was fixed at 35 mg/m2, every 3 weeks.
      The dose of alpha-2b IFN was 6 million U/m2 per day, 5 days a week. 3 patients
      (14%) obtained a partial response lasting 11, 16 and 30 months, and 1 had a
      stable disease during 8 months. The other 17 patients died within a median
      survival time of 4 months. All patients experienced flu-like symptoms. 7 patients
      experienced WHO grade III-IV haematological toxicity. We conclude that the
      association of alpha-2b IFN and doxorubicin is feasible, with respect to the use
      of doxorubicin at an inferior dose level than the same agent used without IFN.
      The response rate is comparable to that observed with doxorubicin used alone.
      Further phase I studies and randomised trials are required to confirm the role of
      this regimen in the treatment of unresectable hepatocellular carcinoma.

PMID- 7528032
TI  - Ovarian ablation as treatment for young women with breast cancer.
AB  - Ovarian ablation has been used for breast cancer treatment for nearly 100 years.
      Available methods of causing ovarian failure include surgical or radiotherapeutic
      ablation and LH-RH agonists that effect a reversible "medical oophorectomy." In
      addition, administration of certain types of chemotherapy to susceptible hosts
      may also result in permanent amenorrhea. The response rate to ovarian ablation in
      premenopausal women with metastatic breast cancer is about 35%. It is more
      effective in women over 35 years of age or with estrogen receptor-positive
      tumors. Oophorectomy, ovarian radiation, and luteinizing hormone-releasing
      hormone agonists are probably equally effective in this setting, although
      rigorous comparative trials have not been completed. Individual trials of ovarian
      ablation as adjuvant therapy show a trend toward increased relapse-free survival,
      but rarely show a survival advantage. However, an overview analysis of randomized
      trials of adjuvant ovarian ablation, which includes about 1800 women under 50
      years of age, suggests that this modality reduces the annual rates of recurrence
      and death by about 25%, an effect similar to that seen with adjuvant chemotherapy
      by indirect comparison. Therefore, a number of clinical trials designed to
      elucidate the role of ovarian ablation alone or in conjunction with other
      adjuvant approaches are in progress. The routine use of ovarian ablation as an
      adjuvant therapy should await the establishment of its efficacy in these trials.

PMID- 7528033
TI  - [Palmar burns of the hand in children. 81 cases].
AB  - The authors reviewed 81 children between the ages of 5 months and 3 years
      suffering from palmar burns of hands from 1988 to 1992. Most burns were
      unilateral (53), superficial 2nd degree (48), due to contact (55), in boys (48)
      and only affecting the palm (69). The initial treatment consisted of directed
      healing followed by a split-skin graft in 8 cases. The initial scar was not
      retracted in 58 cases, retracted in 17 cases and hypertrophic in 8 cases. 79% of
      children had no sequelae at 12 months. At more than three years, 15% of children
      (12) had sequelae: 9 adhesions of the first commissure, 5 flexion deformities of
      long fingers, 3 clinodactylies, 1 syndactyly. All were operated by trident
      plasties, Colston flaps or full-thickness skin graft. A final functional
      assessment was performed. 90% of children had no sequelae. Four children still
      presented moderate functional discomfort (3 adhesions of the first commissure
      requiring reoperation, one case of decreased sensitivity). Palmar burns in
      children have a good prognosis. Factors of severity are: involvement of the 1st
      commissure, associated dorsal burn, deep 2nd degree, poor social conditions,
      delayed management.

PMID- 7528031
TI  - High-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow
      support in women with measurable advanced breast cancer responding to standard
      dose therapy: analysis by age.
AB  - The analysis was undertaken to determine if the time to progression and survival
      for women with breast cancer treated with high-dose chemotherapy after a
      conventional-dose induction therapy differs significantly for women younger and
      older than 40 years of age. All patients treated in phase II or III protocols of
      high-dose chemotherapy for breast cancer are included in this analysis. Women
      were treated on one of six protocols: four sequential phase II protocols for
      metastatic breast cancer involving cyclophosphamide at a dose of 6000 mg/m2,
      thiotepa at 500 mg/m2, and carboplatin at 800 mg/m2 (CTCb) chemotherapy; one
      phase II study of CTCb chemotherapy for stage III or inflammatory breast cancer;
      and a Cancer and Leukemia Group B phase III study of cyclophosphamide,
      carmustine, and cisplatin for women with more than 10 involved lymph nodes after
      primary therapy. Eligibility criteria for the patients with metastatic disease
      included histologically documented breast cancer, at least a partial response to
      conventional dose therapy, no prior pelvic radiotherapy, cumulative doxorubicin
      of less than 500 mg/m2, and physiologic age of 18-55 years. Patients with
      inadequate renal, hepatic, pulmonary, and cardiac function or tumor involvement
      of marrow or central nervous system were excluded. Of 99 registered patients,
      three (3%) died of toxicity. There were no toxic deaths in protocols for stage II
      and III disease, and to date none of these patients have relapsed. Thus, there
      are no differences by age for these studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528034
TI  - [The strategy of the finger bank].
AB  - The authors present 40 cases of multidigital amputations with a "bank-finger"
      reconstruction. They use of flaps, tendons, nerves grafts .... from the injured
      finger. Moreover, they propose a guide in the use of heterotopic implantations,
      in emergency and in secondary. The indications of the digital translocation is
      discussed about the priority finger and the localisation of the others fingers to
      be reimplanted. They make mention of the rare possibility of temporary ectopic
      implantation.

PMID- 7528035
TI  - [Reconstruction of the long fingers using toe transfers].
AB  - The authors review 29 toes transfers on 24 patients with injury of long fingers
      between 1985 and 1990. The series contains 16 complete toes and 13 partial toes
      transfers. The results, inconvenience and indications are discussed.

PMID- 7528037
TI  - [Deformities of the fingers secondary to fingersucking].
AB  - After prolonged finger-sucking in early infancy, skeletal digital deformities,
      especially of the index finger, may occur. Thumb-sucking causes primarily dental
      disturbances whereas prolonged index--sucking may deform this finger, with
      functional as well as aesthetic consequences on the grip. Acquired rotation of
      the index finger is the most frequent deformity and does not always resolve
      spontaneously so that a rotation osteotomy had to be performed in 3 cases.

PMID- 7528038
TI  - [Villonodular synovitis of the wrist. Apropos of a case in an adolescent].
AB  - Pigmented villonodular synovitis of the wrist is an uncommon disease. It is also
      very rare in childhood and adolescence. The authors report a case with good
      outcome after surgery and review the literature concerning this.

PMID- 7528039
TI  - True aneurysm of digital artery in hemophilia. A case report.
AB  - A case of a true aneurysm of the radial digital artery of the thumb is presented.
      Treatment by ligation and excision resulted in relief of symptoms. To our
      knowledge, this is the first reported case of true digital aneurysm of the thumb.

PMID- 7528036
TI  - [A classification proposal for compression-flexion articular fractures of the
      distal extremity of the radius. A radiographic study of 40 cases].
AB  - 40 articular fractures of the distal radius with palmar displacement, have been
      analyzed with Roentnograms. An original classification is proposed for a better
      initial evaluation of detailed articular damages and displacement. 4 main
      different types of fracture are described considering for elementary fragments
      constituted with antero-medial margin, radial styloid and dorsal margin; type A:
      total anterior margin, type B: separated anterior margin, type C: antero-lateral
      margin, and type D: antero-medial margin. The two types I and II described by
      Cauchoix, Duparc and Postel concerning the integrity of the dorsal margin have
      been incorporated. The quantity of radial gene fractured is determined on lateral
      view: < 1/2, > or = 1/2, and total. Finally the displacement is typed: anterior
      dislocation, or anterior translation. An original case of volar dislocated
      fracture with an intact radial styloid is reported. This classification could
      drive to specific orientations for treatment: even external fixation often
      associated with pinning, or alternative buttress plating.

PMID- 7528041
TI  - [The organization of hand rehabilitation in France in 1993].
AB  - Analysis of a questionnaire sent to members of the French Hand Society revealed
      the following information: the concept of a surgical team is very important,
      physiotherapists are usually our primary coworkers. Splints are frequently
      prescribed and must correspond to precise criteria. Surgeons are globally
      satisfied with their practice and their results, but are dissatisfied with the
      nomenclature concerning medical splints. Analysis of this nomenclature reveals
      marked inequalities concerning prices and refunds.

PMID- 7528040
TI  - Monostotic fibrous dysplasia in the hand. A case report.
AB  - We present in this paper a new case of monostotic fibrous dysplasia in the hand.
      The reason for this communication is the rarity of this osseous dystrophy in the
      hand as well as its radiologic features as a malignant osseous tumor, being a
      lytic lesion with incomplete periostic reaction.

PMID- 7528042
TI  - Merkel cells in neurofibromas and neurilemomas.
AB  - Merkel cells are an integral component of the cutaneous nervous system. They are
      commonly associated with dermal nerves under normal physiological conditions. We
      postulated that Merkel cells may be present in increased numbers within the
      epidermis overlying benign peripheral nerve sheath tumours such as neurilemomas
      and neurofibromas. Paraffin-embedded skin biopsy specimens from 21 patients with
      neurilemomas and 26 with neurofibromas, were analysed for the presence of Merkel
      cells using a standard immunohistochemical assay (avidin-biotin-peroxidase
      complex system) with an antibody to cytokeratin 8 (CAM 5.2). Ten cases of
      leiomyomas were examined as controls. Merkel cells were identified in the
      interfollicular area of the basal cell layer overlying 14 of 21 (67%)
      neurilemomas and nine of 26 (35%) neurofibromas. Merkel cells were more
      frequently observed in increased numbers in a linear array within the basal cell
      layer in neurilemomas than in neurofibromas, where they were found as individual
      cells. No Merkel cells were found in the epidermis overlying leiomyomas. The
      results of this study suggest that Merkel cells are quantitatively increased in
      the basal cell layer of the epidermis overlying benign peripheral nerve sheath
      tumours, particularly neurilemomas.

PMID- 7528043
TI  - Bleomycin-induced flagellate dermatitis: a clinical and histopathological review.
AB  - We report a case of bleomycin-induced flagellate dermatitis. Our patient
      developed pruritic linear lesions 4 days after her first dose of bleomycin. A
      closed patch test was performed, and was negative. However, on rechallenge, the
      linear eruption recurred in the previously involved sites, and in new sites,
      within 24 h. Flagellate dermatitis is a characteristic reaction to bleomycin use,
      but varying histological features and clinical presentations may be seen.

PMID- 7528044
TI  - Pulmonary platelet trapping induced by bleomycin: correlation with fibrosis and
      involvement of the beta 2 integrins.
AB  - Platelet trapping was explored during the course of bleomycin induced pulmonary
      fibrosis by the injection of indium-111 labelled platelets and by light and
      electron microscopy (EM) of the alveolar capillaries. An i.v. injection of
      bleomycin markedly increased the localization of labelled platelets in the lung
      (but not in other organs) for about 3 weeks. On day 7 after bleomycin injection,
      a significant increase in the number of platelets in contact with the alveolar
      endothelium was seen with EM. Platelet trapping was strongly correlated (P <
      0.005) with collagen deposition when examined in mouse strains genetically
      susceptible (CBA, C57BL/10, BL10 A.2R), or resistant (Balb/c, BL10.D2, BL10.A),
      to bleomycin induced fibrosis. In addition, several treatments known to decrease
      bleomycin induced collagen deposition and synthesis, namely administration of
      antibodies against CD11a, CD11b, TNF-alpha and IL-1ra, also decreased platelet
      trapping. As evaluated by EM, anti CD11a mAb significantly decreased the number
      of platelets in contact with the alveolar endothelium. This study indicates that
      bleomycin induced pulmonary fibrosis is strongly correlated with platelet
      trapping and that platelets probably interact, via their CD11a, with the CD54
      born by the alveolar endothelium.

PMID- 7528045
TI  - Inter-alpha-trypsin inhibitor polymorphism. An improved phenotyping procedure and
      two new alleles.
AB  - Serum samples treated with chondroitinase ABC and sialidase were investigated for
      the detection of inter-alpha-trypsin inhibitor (ITI) polymorphism. The improved
      phenotyping procedure has proved to be the most practical method for ITI
      phenotyping. The ITI allele frequencies were examined in 2 population samples
      from Japanese (n = 365) and Thais (n = 150). Three common alleles, ITI*1, ITI*2,
      and ITI*3 were identified in both populations, but the Thai population showed a
      higher frequency of ITI*1 and a lower frequency of ITI*3. Two new alleles were
      found, which were tentatively denoted ITI*Y and ITI*T. The ITI*T allele frequency
      in Thais was 0.047.

PMID- 7528047
TI  - Sequence and expression of human hair keratin genes.
AB  - Normal hair growth and differentiation requires co-ordinate expression of many
      hair specific structural protein genes. It has been established that one of the 4
      major groups of hair structural proteins, low-sulphur hair keratins, belongs to
      the intermediate filament (IF) multigene family. Hair keratin IF proteins differ
      from those of other epithelia as they contain cysteine-rich terminal domains
      allowing more extensive disulphide bonding to the high-sulphur hair matrix
      proteins. Until recently, little information concerning the primary sequence of
      hair keratins was available but cloning of some mouse hair and sheep wool
      keratins has now been reported. Using these sequences, we have polymerase chain
      reaction (PCR) amplified genomic fragments of human hair-specific keratin IF
      genes and isolated cosmid clones containing full length genes. We have sequenced
      part of these genes and studied their expression in human hair follicles. Hair
      specific keratin fragments were amplified from placental gDNA by PCR primed with
      synthetic oligonucleotides. Fragments were cloned and sequenced after ligation
      into pGEM-3Z and labelled riboprobes were generated for in situ hybridization on
      human skin sections. A human cosmid library was screened with PCR fragments and
      clones encoding human hair keratin genes were characterised by southern
      hybridization and sequencing. The type I human hair-specific keratin clones
      obtained (HaKA1-b2, 386 bp; hHaKA1-XH1, 1202 bp) encoded 2B helix, C-terminal and
      3'nc regions and were 65% homologous to mouse sequences. The type II hair keratin
      clone (hHaKB2-1, 829 bp) also encoded 2B helix and C-terminal regions and was 95%
      homologous to mouse. In situ hybridization on human skin sections showed a
      specific reaction with precortical cells of the hair follicle. One human cosmid
      clone, isolated with the hHaKB2-1 probe, contained two type II hair keratin genes
      about 7 kb apart, each of which had 9 exons spanning approximately 6 kb. The
      coding sequences were homologous to mouse cDNA (77-88%). These human hair
      specific keratin clones are useful molecular tools for studies of hair
      differentiation.

PMID- 7528046
TI  - Immunohistochemical examination of skin wounds with antibodies against alpha-1
      antichymotrypsin, alpha-2-macroglobulin and lysozyme.
AB  - The distribution of the proteinase inhibitors alpha-1-antichymotrypsin (alpha 1
      act), alpha-2-macroglobulin (alpha-2-m) and lysozyme was analysed
      immunohistochemically in 27 intravitally acquired wounds, 3 postmortem skin
      lacerations and 9 specimens of undamaged skin. Intravitally acquired wounds
      demonstrated distinct positive reactions for all antibodies examined (alpha-1-act
      66.6%; alpha-2-m 51.9%; lysozyme 25.9%). However the undamaged skin margins
      opposite the wound margins also gave positive reactions (alpha-1-act 51.8%; alpha
      2-m 37.0%; lysozyme 25.9%). Nearly half of the control cases (specimens of
      undamaged skin) exhibited weak positive reactions for all 3 antibodies. These
      could be easily distinguished from the strong positive reactions observed in
      intravitally acquired wounds. False positive reactions were observed due to
      contamination resulting from contact with serum components, in cases of advanced
      autolysis of specimens, and as a result of fixation and drying artefacts. Even
      though immunohistochemical studies of alpha-1-act, alpha-2-m and lysozyme give
      some indications concerning wound vitality, they cannot be considered as proof
      because irrefutable differentiation of true positive and false positive reactions
      is not possible in all cases.

PMID- 7528048
TI  - Genetic disorders of keratin: are scarring alopecias a sub-set?
AB  - Recent advances have challenged the prevailing view that keratins are merely
      passive bystanders of keratinocyte biology. With the exciting discovery that
      three autosomal dominant genetic skin disorders, epidermolysis bullosa simplex
      (EBS), epidermolytic hyperkeratosis (EHK) and palmoplantar keratoderma (PPK), are
      in fact disorders of keratins comes the realization that the integrity of the
      keratin filament network is crucial to the structural integrity of the skin.
      Since it has been recently established that mutations in keratins K5/K14, K1/K10
      and K9 are causative for these keratinocyte disorders, it is very likely that
      mutations in K6 or in its obligate partner, K16 will result in disease. In order
      to test this we have produced transgenic mice that express a mutant K6 gene.
      These mice develop a progressive scarring alopecia at about 6 months of age.
      Later, the denuded areas developed a keratosis which was prone to infection.
      Ultrastructural analysis suggests that hair loss is due to the destruction of the
      outer root sheath. We believe that these mice are models of another keratin
      disorder.

PMID- 7528049
TI  - Human hair production by scalp samples grafted onto nude mice. Biochemical data
      on normal human hair and the genetic defect trichothiodystrophy.
AB  - The authors report on a laboratory model for continuous production of human hair
      during long periods of time. This study shows that the amino acid composition of
      hairs collected in situ from human scalp was similar to that of terminal hairs
      produced by the donors' scalp follicles grafted and maintained onto nude mice. A
      similar experiment was performed with scalp samples from a foetus with
      trichothiodystrophy (TTD). The amino acid analysis of TTD lanugo hairs and of the
      TTD shafts produced by grafted scalp specimens was consistent with findings
      published in the literature: severe decrease of cys (< 50% of control values) and
      moderate decrease of thr and pro (80% of control values or less) with an increase
      of ala-asp-ile-leu-lys-met-phe (120% of control values or more). These changes
      indicate a decrease of high sulphur proteins (HSP) and consequently a relative
      increase of keratins. Furthermore, when foetal scalp samples were grafted, the
      lanugo hairs transformed into terminal hairs along with normal initiation of
      melanisation. Hence, keratin and HSP gene expression and regulation of
      melanogenesis in the normal and genetically defective TTD human hair follicle
      grafts appear to be independent of systemic host-related factors, at least during
      a 6 months follow-up period after grafting. The present experimental evidence
      further supports conclusions gained from previous assays with normal and TTD
      variant scalp grafts, i.e. that the nude mouse bearing human scalp specimens may
      serve as a clinically relevant laboratory model for evaluating regulation of
      normal and abnormal gene expression in the hair follicle under well controlled
      experimental conditions.

PMID- 7528050
TI  - Hair growth-stimulating effects of cyclosporin A and FK506, potent
      immunosuppressants.
AB  - Cyclosporin A (CsA), a cyclic endecapeptide, is a T cell-specific
      immunosuppressant and is successfully used in the field of organ transplantation.
      Another T cell-specific immunosuppressant, FK506, a more recently discovered
      macrolide antibiotic, is effective against graft rejection at much lower doses
      than CsA. Although totally different in structure, both compounds inhibit T cell
      activation by interfering with the production of interleukin-2 (IL-2) by
      inhibiting IL-2 gene expression, probably through the inhibition of calcineurin,
      a Ca2+/calmodulin-dependent phosphatase. Clinical studies have revealed that
      FK506 induces a variety of side effects in common with CsA. One of the most
      common side effects of CsA is hypertrichosis. The hair growth stimulating effect
      of CsA is observed not only in normal but also in pathological conditions of hair
      growth, i.e. in patients with alopecia areata and also in some patients with male
      pattern alopecia. Although hypertrichosis is induced by both topical and oral
      administration of CsA, there has been no report showing that FK506 induces
      hypertrichosis. Recently we have found that topical application of FK506 to skins
      of mice, rats and hamsters markedly stimulates hair growth. This hair growth
      stimulating effect of FK506 is observed when applied topically but not by oral
      administration, even with a dose which causes marked immunosuppression. The hair
      growth stimulating effect of FK506 in normal animals may apparently be unrelated
      to its immunosuppressive effect. In vitro studies revealed that FK506 directly
      stimulates hair follicles. Mechanisms of hair growth stimulating effects of FK506
      and CsA remain to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528052
TI  - Maternal relaxin: a determinant of fetal heart rate?

PMID- 7528051
TI  - Pathogenesis in pili torti: morphological study.
AB  - To clarify the mechanism of pili torti formation, hair materials obtained from a
      patient with the typical classical type of pili torti were examined. Light
      microscopy, scanning electron microscopy (SEM), transmission electron microscopy,
      (TEM) and 3-D analysis revealed that: (1) The hair shaft was partly flattened.
      The hairs twisted clockwise or counter-clockwise on their own axis and some hairs
      were knotted. (2) Short hairs showed disruptions at the flattened or unflattened
      regions, at the knot, or at the root of branched hairs caused by longitudinal
      ruptures. (3) Light microscopically, cell vacuolation and irregularity in
      thickness of the outer root sheath (ORS) at the suprabulbar level were seen. At
      the middle to upper levels of the follicles, some eosinophilic pyknotic ORS cells
      were observed scattered around. (4) At the upper levels, the ORS and inner root
      sheath (IRS) partly revealed irregularity of thickness and formed an irregular
      shaped hair canal. (5) By DACM staining, cytoplasmic SH fluorescence showed an
      irregular arrangement of the ORS cells. Some abnormal SH- or SS-positive cells
      were observed scattered throughout the ORS. (6) Ultrastructurally, the
      irregularities in thickness and cell shape of the IRS and ORS became visible at
      the level, where the Henle's layer keratinized. In the hair cortex, there was no
      abnormality of nuclei and the keratin fibers were normally produced, although
      fibers were partially wavy. (7) By 3-D analysis, hair twist was already seen at
      the middle level of the hair follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528053
TI  - Taking account of vaginal bleeding in screening for Down's syndrome.
AB  - OBJECTIVE: To derive a method for revising the risk of Down's syndrome in
      maternal serum marker screening when there is vaginal bleeding. The effect on
      screening performance of routinely allowing for the presence or absence of
      bleeding in all women is also assessed. DESIGN: Overview of published studies on
      the rate of reported vaginal bleeding in pregnancies with Down's syndrome, on the
      rate according to maternal age and on the association of bleeding with alpha
      fetoprotein (AFP) level. The publications are supplemented with data on
      unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG) and AFP levels
      in a consecutive series of screened women. SETTING: Routine Down's syndrome
      screening tests carried out on women having antenatal care at the St James's
      University Hospital, Leeds. SUBJECTS: Eight hundred and nine screened women.
      RESULTS: In five studies the rate of vaginal bleeding in Down's syndrome
      pregnancies was 1.7 times that in unaffected pregnancies on average. In three
      studies, the vaginal bleeding rate increased proportionally by 2.2% on average
      for each year of maternal age. Three studies and our own data were consistent
      with a 10% increase in the mean AFP level associated with vaginal bleeding, but
      it did not appear to materially alter uE3 and hCG levels or the standard
      deviations and correlation coefficients for any of the three analytes. An
      individual woman's risk was calculated by multiplying her age-specific odds of
      Down's syndrome by two likelihood ratios, one relating to the vaginal bleeding
      itself and one from the marker levels. Routine allowance for the presence or
      absence of vaginal bleeding was estimated to increase the detection rate by less
      than 1%. CONCLUSION: Our method is of clinical value in revising the risk when
      there is concern that vaginal bleeding might be responsible for a negative
      maternal serum Down's syndrome screening result. A policy of routinely
      incorporating information on vaginal bleeding in risk estimation for all women
      would have too small an effect on overall screening performance to recommend it.

PMID- 7528054
TI  - First trimester maternal serum pregnancy-associated plasma protein A and
      pregnancy-specific beta 1-glycoprotein in fetal trisomies.
AB  - OBJECTIVE: To examine the potential value of maternal serum levels of pregnancy
      associated plasma protein A (PAPP-A) and pregnancy-specific beta 1-glycoprotein
      (SP1) in the detection of fetal trisomy. DESIGN: Cross-sectional study. SETTING:
      The Harris Birthright Research Centre For Fetal Medicine, King's College Hospital
      Medical School, London, UK and Division of Maternal-Fetal Medicine, Jefferson
      Medical College, Philadelphia, USA. SUBJECTS AND METHODS: Maternal serum PAPP-A
      and SP1 concentrations were measured at 10 to 13 weeks gestation in samples from
      42 pregnancies with fetal trisomy (trisomy 21, n = 29; trisomy 18, n = 9; trisomy
      13, n = 4) and in samples from 210 matched controls. RESULTS: In controls, both
      maternal serum PAPP-A and SP1 increased significantly with gestation and in
      trisomic fetuses levels of both hormones were reduced. However, discriminant
      analysis demonstrated that SP1 did not contribute significantly in the
      distinction between trisomic and control pregnancies. Although levels of PAPP-A
      were reduced throughout the gestational range examined (10 to 13 weeks),
      especially in cases with fetal trisomy 21, the deviation was more pronounced at
      10 to 11 weeks than at 12 to 13 weeks gestation. In 45% of pregnancies with fetal
      trisomy 21 and 70% of pregnancies with trisomies 18 or 13 maternal serum PAPP-A
      levels at 10 to 11 weeks gestation were below the 5th centile of the normal
      range. CONCLUSION: Maternal serum PAPP-A concentration in the first trimester of
      pregnancy may prove to be useful in the prediction of risk for fetal trisomies.

PMID- 7528055
TI  - The management of zygomatic complex fractures--results of a survey.
AB  - A study was undertaken to investigate the current practices in the UK in the
      management of zygomatic complex fractures. The results are presented and
      discussed with reference to recent literature on the subject.

PMID- 7528056
TI  - Serum tumor markers in patients on dialysis and kidney transplantation.
AB  - Tumor markers play an important role in the assessment of patients with some
      types of malignant tumors. We studied the effects of dialysis and transplantation
      on the serum levels of five tumor markers; alpha-fetoprotein (AFP), carcino
      embryonic antigen (CEA), cancer antigen-125 (CA-125), cancer antigen-19.9 (CA
      19.9), and prostate specific antigen (PSA). Serum tumor markers were measured in
      patients who-had been on dialysis treatment or had a renal transplant for at
      least one month. Four groups of 30 patients each (hemodialysis, peritoneal
      dialysis, renal transplant, and normal controls) were studied. Age and sex
      distribution were comparable between the dialysis and control groups, but the age
      was significantly younger in the transplant group. Serum AFP and PSA levels were
      within normal limits in the dialysis and transplant patients. Serum tumor
      markers, which were raised in the hemodialysis and peritoneal dialysis patients
      compared to transplant patients and controls, include: CEA (4.5 +/- 2.7 and 5.1
      +/- 3.0 vs 1.7 +/- 1.2 and 2.7 +/- 1.2, p < 0.001); CA-125 (41.1 +/- 43.8 and
      18.9 +/- 12.7 vs 13.4 +/- 5.7 and 6.1 +/- 4.9, p < 0.001 and p < 0.05); and CA
      19.9 (66.0 +/- 60.4 and 66.2 +/- 76.5 vs 20.2 +/- 12.3 and 5.3 +/- 4.5, p <
      0.001). Raised CEA, CA-125, and CA-19.9 levels were detected in 37%, 10%, and 53%
      of peritoneal dialysis patients and 17%, 27%, and 57% of hemodialysis patients.
      Although the mean serum CEA, CA-125, and CA-19.9 levels were higher in the
      transplant patients compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528057
TI  - Dialysis modality comparison of insulin-like growth factor binding protein-3
      removal in children: could this have a potential growth benefit?
AB  - Centers have reported superior growth in children on peritoneal dialysis (PD) as
      compared to hemodialysis (HD). Many factors may influence this outcome including
      diet, adequacy of dialysis, and control of metabolic acidosis. The role of
      insulin-like growth factor-1 (IGF-1) and its bioactivity in patients with end
      stage renal disease (ESRD) have been recently examined. Insulin-like growth
      factor binding protein-3 (IGFBP-3) has been shown to be elevated in ESRD,
      possibly resulting in inhibition of the bioactivity of IGF-1. Potentially, the
      removal of IGFBP-3 may improve the bioactivity of IGF-1, with resulting
      improvement in growth. The molecular weight of IGFBP-3 (30.5 kDa) is in the range
      of other proteins cleared by PD (e.g., albumin-69 kDa). Therefore, we have
      analyzed 10 samples of IGFBP-3 in the dialysis effluent of 9 children on
      peritoneal dialysis, and have found that the mean level +/- SEM was 0.21 +/- 0.03
      mg/L, while the 3 analyses of children on standard HD was 0.02 +/- 0.01 mg/L. In
      addition, the effluent of 2 children on a high-efficiency dialyzer had an IGFBP-3
      level of 0.45 +/- 0.25 mg/L. Even though quite preliminary, these data may
      suggest another reason for improved growth in children on PD and a potential
      advantage to high-efficiency HD. Further analysis in a larger population of ESRD
      patients will be needed in order to confirm these preliminary findings.

PMID- 7528059
TI  - Serum concentration of a bovine mannan-binding protein reactive with a Ra
      chemotype strain of Salmonella typhimurium: no significant changes associated
      with mastitis.
AB  - The serum concentration of a bovine mannan-binding protein reactive with a Ra
      chemotype strain of Salmonella Typhimurium in sera from cows with or without
      mastitis were determined by sandwich enzyme-linked immunosorbent assay. From the
      results obtained for 10 healthy cows aged 2 to 7 years, mean +/- SD serum
      concentrations of MBP in bovine sera were 77.5 +/- 33.1 micrograms/ml.
      Concentrations in 7 healthy heifer calves aged 6 months were 52.2 +/- 10.2
      micrograms/ml, whereas those in 7 healthy bullocks 65.8 +/- 21.8 micrograms/ml.
      Concentrations in 4 cows aged 4 to 7 years with mastitis were slightly lower (34
      to 72 micrograms/ml). After recovery, the serum concentrations rose to the normal
      concentrations in healthy cows. These findings indicate that the serum
      concentrations of bovine MBP decrease during mastitis, suggesting that bovine MBP
      may not be an acute phase reactant.

PMID- 7528058
TI  - Identification and carbohydrate specificity of a chicken serum mannan-binding
      protein reactive with a Ra chemotype strain of Salmonella typhimurium.
AB  - To compare a chicken serum mannan-binding protein (MBP) with a chicken Ra
      reactive factor (RaRF), both serum proteins were isolated by combination of
      different chromatography. In SDS-PAGE, both purified proteins were resolved into
      a major protein band with a molecular weight of 34,000 and a few minor protein
      bands. In Western blotting with both purified proteins, only a single band with a
      molecular weight of 34,000 was detected with anti-chicken serum MBP antibody,
      indicating that the major protein band of chicken serum MBP and RaRF are
      antigenically identical. The combining sites of these two proteins were most
      reactive with N-acetylmannosamine followed by mannose, N-acetylglucosamine, and L
      fucose. These findings suggest that chicken serum MBP may be identical to its
      corresponding bactericidal factor RaFR in terms of antigenicity and
      monosaccharide specificity.

PMID- 7528060
TI  - Immunohistochemical examination of neural cell adhesion molecule (NCAM), tenascin
      and fibronectin on the development of cartilaginous tissue in canine mammary
      mixed tumors.
AB  - The expression of neural cell adhesion molecule (NCAM), tenascin and fibronectin
      during cartilage-like tissue formation in canine mammary mixed tumor was
      immunohistochemically examined. Mirror-image serial sections revealed that
      proliferating myoepithelial cells simultaneously expressed these adhesion
      molecules where no cartilage-like tissue and no expression of cartilage-specific
      type II collagen were observed. With the formation of cartilaginous tissue,
      positive signals of these adhesion molecules decreased in chondroblast-like
      cells, the cartilaginous tissue was hyalinized and mature chondrocyte-like cells
      no longer expressed these cell adhesion molecules. NCAM, tenascin and
      fibronectin, therefore, may play crucial roles on the proliferation of
      myoepithelial cells and the subsequent development of cartilaginous tissue in
      canine mammary mixed tumor.

PMID- 7528061
TI  - Effect of human recombinant granulocyte-macrophage colony-stimulating factor and
      IL-3 on the expression of surface markers of human monocyte-derived macrophages
      in long-term cultures.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3, which are
      involved in the maturation of cell precursors in the bone marrow into
      granulocytes and macrophages, were found also in chronic inflammatory sites, and
      their production might be enhanced by inflammatory stimulants. These findings led
      us to examine the effect of human recombinant GM-CSF (hrGM-CSF) and hrIL-3 on the
      maturation of human peripheral blood monocytes in long-term tissue cultures and
      on the expression of functional membrane bound molecules. Adherent human
      peripheral blood monocytes cultured for 2 weeks in the presence of GM-CSF or IL-3
      were examined for viability and adherence, expression of membranal HLA-DR, CD-14,
      and IL-1 alpha, and LPS triggered TNF-alpha production. GM-CSF and IL-3 treatment
      increased the viability of adherent cells after 2 weeks in culture, and elevated
      the expression of membranal HLA-DR, CD-14 (LPS receptor), and IL-1 alpha. Such
      treated macrophage cultures also showed elevated production of TNF-alpha. The
      results indicate that GM-CSF and IL-3 facilitate the long-term maturation of
      monocytes into macrophages, augment their capacity to bind LPS, and elevate the
      release of cytokines involved in inflammatory and granulomatous reactions.

PMID- 7528062
TI  - Modulation of cytokine expression in PB-3c mastocytes by IBMX and PMA.
AB  - Stimulation of mast cells, either via the IgE receptor or with calcium ionophore
      triggers the production of several cytokines, such as interleukins-3, -4, -5, and
      -6, and GM-CSF. In PB-3c mastocytes, ionophore-induced IL-3 and GM-CSF expression
      is primarily the result of mRNA stabilization, and is enhanced by oncogenic ras.
      Apart from mobilizing calcium, the IgE receptor activation leads to production of
      DAG and elevation of cAMP levels, thereby activating protein kinases C and A,
      respectively. The influence of these two secondary messengers on cytokine
      production was examined using the cAMP elevating agent IBMX, the phorbol ester
      PMA, and the staurosporine derivative CGP 41251, which preferentially inactivates
      PKC. IBMX was determined to be a potent coinducer of IL-3 expression, whereas
      elevation of IL-6 and GM-CSF was more pronounced in PMA-treated cells. Both PMA
      and IBMX were shown to act posttranscriptionally on IL-3, by extending the half
      life of the mRNA. Ionophore-induced cytokine expression appears to require
      serine/threonine kinase activity, as it could be abolished by treatment with the
      drug CGP 41251. Our results therefore suggest that the factors regulating
      cytokine expression and mRNA stability are subject to regulation by
      serine/threonine phosphorylation.

PMID- 7528063
TI  - [Martin Kirschner: anesthesiologist--intensive care physician--pain therapist].
AB  - The development of numerous modern anaesthetic technics and methods in the mid of
      the twenties and thirties, which had become a main topic of scientific interest
      in the German-speaking countries, is connected with the name of the surgeon
      Martin Kirschner. Reputed as an outstanding surgeon at home and abroad, he
      realised the need of modern anesthetic technics and monitor systems for the
      further progress in all areas of operative medicine. His research enhanced our
      knowledge of the mode of action of various anaesthetic procedures and the
      prevention of iatrogenic complications became a central part of his interest. His
      concept to use a physician-aided rapid transportation system, so that the
      emergency physician comes to the patients and not vice versa, has become an
      integral part of emergency medical system nowadays. Not surprisingly, he asked
      for a physician-controlled transportation of such "high-risk-patients" with the
      aid of aeroplanes. Furthermore, he demanded continuous control of vital
      parameters of such severely injured persons, best realized in an intensive-care
      unit. Comparably modern were his concepts concerning the perioperative sedation
      of patients, operated under any kind of local anaesthesia. Recommending
      advantageous drugs to do so, he suggested the possibility of using a wireless or
      television set, a technique absolutely new at that time, within the operation
      theatre. Reviewing Kirschner's contributions to pain alleviation procedures, we
      can consider him to be a passionate surgeon, but also a surgeon with the
      deliberations and actions of an anaesthesiologist: "Divinum est, sedare dolorem."

PMID- 7528064
TI  - Epitopes on thyroglobulin: a study of patients with thyroid disease.
AB  - Thyroglobulin antibodies (TgAbs) are typically found in autoimmune thyroid
      diseases and, more rarely, in nonautoimmune thyroid diseases and healthy
      subjects. To determine whether TgAbs associated with different conditions
      recognize different epitopes on the thyroglobulin molecule, we studied 28
      patients with Hashimoto's thyroiditis, 30 with Graves' disease, 21 with thyroid
      carcinoma, 18 with nontoxic goiter, and 25 healthy subjects. All patients were
      selected for the presence of TgAbs; 4/25 healthy subjects also had TgAbs. The
      sera were assayed for the their ability to inhibit the binding of monoclonal
      antibodies to thyroglobulin in an ELISA assay. We found that: 1) TgAbs in
      Hashimoto's patients preferentially recognized three clusters of epitopes (II,
      III and typically VI), with no difference between the goitrous and the atrophic
      variants; 2) TgAbs in Graves' patients were directed toward cluster II, with no
      difference between the presence or the absence of ophthalmopathy; 3) TgAbs in
      thyroid carcinoma patients recognized the same clusters as Hashimoto's patients;
      4) TgAbs in nontoxic goiter patients and in the four healthy subjects showed no
      restriction in epitope recognition. We suggest that in individuals with no overt
      clinical or biochemical thyroid abnormalities but with TgAbs, the finding that
      these TgAbs recognize particular immunodominant clusters may be utilized to
      predict full-blown thyroid disorders. Longitudinal studies are needed to evaluate
      the possible clinical application of this methodology.

PMID- 7528067
TI  - Effects of interleukin-4 on granulocyte-macrophage-colony formation from murine
      bone marrow cells and hematopoietic reconstitution following murine allogeneic
      bone marrow transplantation.
AB  - We investigated the effects of mouse recombinant IL-4 on hematopoiesis in vitro
      and in vivo. IL-4 alone was found to be incapable of stimulating colony
      formation, but it inhibited both IL-3 and GM-CSF-induced colony formation by
      murine hematopoietic progenitor cells. In contrast, colony formation induced by G
      CSF was enhanced in the presence of IL-4. We also studied the influence of IL-4
      on hematopoietic reconstitution after allogeneic bone marrow transplantation in a
      murine model, and found that IL-4 had significant inhibitory effects on
      neutrophil recovery and that neutrophil recovery accelerated by IL-3 and G-CSF
      was significantly suppressed by IL-4. The combination of IL-4 and GM-CSF caused a
      significant decrease in the absolute number of neutrophils.

PMID- 7528066
TI  - The release of glandular kallikrein from submaxillary glands of rats exposed to
      heat.
AB  - The salivary flow elicited by phenylephrine was reduced in kininogen-deficient
      rats or by pretreatment of normal Wistar rats with HOE 140, a bradykinin
      antagonist. Salivary flow induced by substance P was similar in normal and
      kininogen-deficient rats. Phenylephrine released large amounts of kallikrein in
      saliva. Isoproterenol was less active while pilocarpine and substance P induced a
      small secretion of kallikrein. The saliva produced by anaesthetized rats in
      response to heat stress contained low levels of kallikrein. However a large
      depletion of the kallikrein content of submaxillary glands was observed in awake
      animals exposed to 36 degrees C and 40 degrees C for one hour. This depletion was
      suppressed by prazosin administered with a beta-adrenergic antagonist.
      Administered alone, these drugs had no effect, whereas atropine increased the
      depletion. The presence of kallikrein was observed in the oedema fluid which
      developed around the submaxillary glands in rats pretreated with atropine or
      exposed to 40 degrees C. A consumption of plasma kininogens occurred during heat
      exposure. The reflex-induced release of kallikrein during heat exposure is mainly
      controlled by sympathetic nerves through activation of both alpha and beta
      adrenoreceptors. This release induces the formation of kinins which participate
      to the thermolytic salivation.

PMID- 7528069
TI  - Preservation and contrast without osmication or section staining.
AB  - Conventional treatment of tissues for sectioning and transmission electron
      microscopy uses aldehyde fixation and osmium tetroxide postfixation. Although the
      result is aesthetically pleasing, osmication destroys some cell components and
      reduces the chemical activity of others, such as reaction with antibodies and
      lectins. We have found that aldehyde fixation followed by uranyl acetate
      preserves and contrasts most structures and visualizes some that are not easily
      seen after osmication. Aldehyde/UA treated tissues have enough contrast to be
      observed without section staining while retaining some of the chemical activity
      that is lost through osmication. Sections of tissues with good preservation and
      contrast can be used for immunogold and lectin-gold labelling of at least some
      molecules.

PMID- 7528070
TI  - A negative contrast stain for ultra-thin frozen sections.
AB  - Ultra-thin frozen sections are ideal substrates for immunolabelling in high
      resolution electron microscopy. However, visualization of subcellular structures
      is inferior to that obtained with corresponding plastic sections. Although
      negative staining is generally effective and even superior to positive staining,
      the accumulated stain is often too heavy, obscuring morphology and markers used
      for immunocytochemical localization of antigens. This paper describes the
      development of a modified negative contrast staining technique in which a high
      concentration of uranyl acetate is mixed with methyl cellulose at a low pH.
      Application of this stain to cryosections of cells and tissue resulted in
      improved visualization of morphological structures characterized by negative
      images of membranes and cell organelles. Use of this stain is advantageous for
      morphological and immunocytochemical studies involving ultra-thin frozen
      sections.

PMID- 7528065
TI  - Xanthine oxidase activation in cerulein- and taurocholate-induced acute
      pancreatitis in rats.
AB  - Oxygen free radicals (OFR) are postulated to play a role in the pathogenesis of
      acute pancreatitis. The aim of this work was to examine the role of xanthine
      oxidase in the generation of OFR and the activity of the endogenous defense
      mechanisms as reflected by pancreatic superoxide dismutase (SOD) activity in a
      model of edematous pancreatitis induced in rats by administration of cerulein at
      supramaximal doses, as well as in necrohemorrhagic model induced by intraductal
      administration of sodium taurocholate. Comparison between these two models of
      pancreatitis suggests important differences in origin and importance in the
      evolution of injury. In necrohemorrhagic pancreatitis OFR can be produced by
      xanthine oxidase activity probably associated to cell death. By contrast, in
      cerulein induced pancreatitis, other sources of oxygen free radicals, such as
      inflammatory cells, can be of more importance.

PMID- 7528068
TI  - Antitumor activity of immunoconjugates composed of boanmycin and monoclonal
      antibody.
AB  - Boanmycin (bleomycin A6, BM), an antitumor antibiotic, was conjugated to
      monoclonal antibodies including R19, H111 and CCT2. The immunoconjugates
      exhibited selective cytotoxicity to related target cells including cecum cancer
      Hce-8693 cells, liver cancer BEL-7402 cells and leukemia CEM cells. They were
      highly effective against related human tumor xenografts in nude mice, and the
      inhibition rates by the conjugates were much higher than those by free BM. The
      inhibition rate by R19-BM conjugate against human cecum cancer xenografts reached
      90%. BY immunoelectron microscopy, CCT2-BM conjugate showed specific binding and
      internalization in leukemia CEM cells. The results indicate that boanmycin
      monoclonal antibody immunoconjugates are highly active both in vitro and in vivo.

PMID- 7528072
TI  - [Health screening at school entry--foreign models and prospective
      considerations].
AB  - In Germany, all pupils are subjected to medical examination at school entry. This
      is in fact one of the primary tasks of the School Health Services in respect of
      importance and the amount of work involved. Nevertheless, neither are these
      results properly evaluated, nor has their epidemiological relevance been
      explored. The examination criteria are not uniform, and results are therefore
      greatly at variance. This has given rise to much criticism when comparing the
      german approach to that in other countries. With particular reference to
      experiences in Great Britain, Australia and the Netherlands, we should discourage
      a general medical examination at school entry that focuses on the status of each
      individual from a medical point of view, as has been the practice in Germany to
      date. Instead, selective examinations should be performed with greater emphasis
      on expert pedagogic knowledge with the aim of assessing whether a child is
      mentally and sociologically sufficiently mature to attend school (the German term
      for this concept is "Schulreife", a non-translatable word somewhat equivalent to
      "school age maturity").

PMID- 7528073
TI  - Lindane residues in the water of the Iliki Lake, Greece.

PMID- 7528074
TI  - Propofol protects cultured rat hippocampal neurons against N-methyl-D-aspartate
      receptor-mediated glutamate toxicity.
AB  - The effect of propofol on the toxicity induced by glutamate (GLU), N-methyl-D
      aspartate (NMDA), kainate (KA), and amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) was investigated on cultured fetal rat hippocampal neurons.
      The degree of neuronal injury was quantified by measuring the release of the
      neuron-specific enolase (NSE) into the culture media. The toxicity induced by
      brief exposure to GLU (10(-4) M) or to NMDA (10(-4) M) was significantly reduced
      by propofol, whereas that elicited by KA, AMPA (10(-4) M), or long GLU exposure
      was unaffected. In conclusion, high concentrations of propofol significantly
      attenuate NMDA receptor-mediated glutamate neurotoxicity in vitro. Further
      studies are needed to confirm this beneficial effect in vivo and to evaluate
      propofol as a neuroprotective anesthetic agent in pathologies involving glutamate
      release and NMDA-mediated toxicity.

PMID- 7528075
TI  - Frequency of metastasis in Syrian hamster tumor cells selected for low levels of
      "typical" multidrug resistance.
AB  - The metastatic capability of cells at the initial stages of selection for
      "typical" (P-glycoprotein-mediated) multidrug resistance (MDR) was studied. Two
      independent sublines, 2SC/4-1 and 2SC/4-2 (11-12.4-fold resistant), and their 23-
      to 23.7-fold resistant 2SC/20-1 and 2SC/20-2 variants were isolated from highly
      tumorigenic (TrD50 = 10 cells) and highly metastatic Rous sarcoma, virus
      transformed Syrian hamster fibroblast HET-SR-2SC-LNM line for resistance to
      colchicine. 2SC/4 cells were less tumorigenic (TrD50 = 70 cells) but as highly
      metastatic as parental counterparts. In contrast, both 2SC/20 variants showed a
      decrease in tumorigenicity (TrD50 = 320 cells) and in the capability to produce
      spontaneous distant metastases. 2SC/20 cells almost lost the ability to colonize
      lungs in experimental metastasis assay. The autophosphorylation of pp60src
      tyrosine kinase in 2SC/20 cells was unaltered. The results suggest that i)
      selection of tumor cells for low levels of "typical" MDR leads to a decrease in
      the frequency of spontaneous and experimental metastases, and ii) alterations of
      malignancy in these cells are not caused by an impairment of function of a
      transforming oncogene.

PMID- 7528071
TI  - Eosinophil viability-enhancing activity in mite-sensitive bronchial asthma.
AB  - We examined the eosinophil viability-enhancing activity (EVEA) of peripheral
      blood mononuclear cells (PBMNCs) obtained from 6 patients with mite-sensitive
      bronchial asthma (BA) and 9 normal control subjects. Mite concentrations of 1
      microgram/ml and 10 micrograms/ml significantly increased EVEA in PBMNC culture
      supernatants from BA patients compared with PBMNCs from normal control subjects
      (76.1 +/- 11.0% at 10 micrograms/ml and 56.3 +/- 16.0% at 1 microgram/ml vs 20.6
      +/- 12.6% at 10 micrograms/ml and 7.4 +/- 2.3% at 1 microgram/ml; p < 0.05). The
      level of IFN-gamma in PBMNC culture supernatants in BA patients was 2.3 +/- 0.9
      IU/ml and in normal control subjects 0.7 +/- 0.3 IU/ml. A combination of mAbs
      (anti-IL-3, anti-IL-5 and anti-GM-CSF, with or without anti-IFN-gamma)
      neutralized the EVEA (p < 0.001, p < 0.001, respectively). Dexamethasone (10(-8)
      M to 10(-5) M), cyclosporin A (10(-7) M to 10(-5) M) and FK506 (10(-8) M to 10(
      6) M) significantly inhibited EVEA in BA patients (p < 0.05 to p < 0.001). The
      release of eosinophil cationic protein (ECP) from eosinophils in the presence of
      mite-stimulated PBMNC culture supernatants was higher in patients with bronchial
      asthma (569 +/- 147 micrograms/l) than in normal control subjects (203 +/- 99
      micrograms/l; p < 0.05).

PMID- 7528076
TI  - VLA-2 mediates the interaction of collagen with endothelium during in vitro
      vascular tube formation.
AB  - A confluent endothelial monolayer can be induced to form vascular tubes in
      response to collagen. We investigated possible mechanisms of collagen-induced
      tube formation by using antibodies to the VLA-2 integrin receptor and protein
      kinase C inhibitors. Pre-incubation of cells with anti-VLA-2 (which recognises
      both the alpha 2 and beta 1 chains) and AK7 (which recognises only the alpha 2
      chain) showed a dose-dependent inhibition of tube formation. At 50 micrograms/ml,
      anti-VLA-2 completely inhibited collagen-induced tube formation, whereas AK7
      caused only partial inhibition. Both chlorpromazine and trifluoperazine, at
      concentrations of 10 microM, prevented tube formation (> 40% inhibition). In
      summary, the VLA-2 integrin receptor plays a role in the induction of tube
      formation by type I collagen. Protein kinase C may be activated during this
      process.

PMID- 7528077
TI  - [Palindromic rheumatism disclosing Whipple's disease. Study of 2 personal cases].
AB  - Two patients with palindromic rheumatism were diagnosed with Whipple's disease 5
      years after onset of the joint symptoms. Twenty-one previously published cases of
      Whipple's disease with palindromic rheumatism as the first manifestation were
      identified. Statistically significant differences were found between palindromic
      rheumatism in patients with and without Whipple's disease. Patients with
      Whipple's disease were more likely to be male and to exhibit fever and elevated
      erythrocyte sedimentation rates during joint symptom flares, whereas they were
      less likely to have involvement of the metacarpophalangeal and proximal
      interphalangeal joints. None of the patients with Whipple's disease had either
      skin manifestations of palindromic rheumatism (nodules or paraarthritis) or
      positive tests for rheumatoid factor. Patients with palindromic rheumatism
      exhibiting these features should have an intestinal biopsy to look for Whipple's
      disease.

PMID- 7528079
TI  - Isolation of a gametophyte-specific cDNA encoding a lipoxygenase from the red
      alga Porphyra purpurea.
AB  - A cDNA clone encoding a lipoxygenase was obtained from a subtracted cDNA library
      specific for the gametophyte of Porphyra purpurea. The amino acid sequence of the
      P. purpurea lipoxygenase is most similar to the sequences of animals and plants
      in the iron-binding, catalytic region located in the C-terminal half of the
      enzymes. Northern hybridization confirmed that the gene represented by this cDNA
      is expressed only in the gametophyte.

PMID- 7528081
TI  - Transcriptional regulation of the four promoters of the agarase gene (dagA) of
      Streptomyces coelicolor A3(2).
AB  - The agarase gene (dagA) of Streptomyces coelicolor A3(2) is transcribed from four
      promoters that are recognized by at least three, and probably four, different RNA
      polymerase holoenzymes, each containing a different sigma factor. S1 nuclease
      protection studies revealed that transcription from all four promoters is induced
      by the products of agar hydrolysis and strongly repressed by glucose. Mutants
      deficient in glucose kinase activity were defective in glucose repression of all
      four promoters. Mutants were isolated or identified in which transcription from
      all four promoters had become inducer-independent (i.e. constitutive),
      establishing the existence of a repressor gene for dagA that does not appear to
      be located within 9 kb of the structural gene. The cloned dagA gene was also
      constitutively expressed in the closely related strain Streptomyces lividans,
      which does not normally make agarase and which presumably lacks the repressor
      gene. Glucose was still able to repress dagA transcription even under conditions
      of constitutive expression, suggesting that glucose kinase does not mediate its
      effect via inducer exclusion. Relative differences in the use of the four
      promoters were not detected during different stages of growth of surface-grown
      cultures, although dagA transcription appeared to peak during the production of
      aerial mycelium.

PMID- 7528078
TI  - A noninvasive method for recording the electrical activity of the human uterus in
      vivo.
AB  - Development of an electrohysterograph (EHG) for recording the electrical activity
      of the uterus in vivo has been blocked for 60 years by problems with artifacts
      and extraneous/reactive electrical activity. This study reevaluates a method of
      cervical recording that does not appear to have these limitations. A set of
      cervical electrode cups was used to record uterine activity of 33 normal subjects
      and patients who had dysmenorrhea, endometriosis, or chronic pelvic pain. The
      electrode cups were atraumatic, able to be fitted to all subjects, and showed
      exceptional positional stability. Unipolar and bipolar recordings from the cervix
      showed the same infrequent spikes and spike bursts reported from other studies
      along with continuous, mildly irregular, undulating slow-wave activity, which was
      present throughout the recordings. The frequencies and amplitudes of these slow
      waves changed in relation to exogenous estrogen, diagnosis, intrauterine
      catheters, and the intensity of the subject's pain. Spikes and spike bursts were
      common only during menses and at midcycle. The cervical electrode cups proved
      easy to use and were well accepted by the subjects. The findings indicated that
      the spikes and slow waves were probably uterine in origin and not artifact or
      extraneous/reactive activity. There were also direct and indirect indications
      that the slow waves may represent the ionic propagation of uterine
      electrophysiologic activity through a network of uterine intercellular ionic
      channels (gap junctions). The limited but fairly consistent evidence from a
      number of perspectives indicates that recording spike and slow-wave activity from
      the cervix is a viable and practical EHG method.

PMID- 7528083
TI  - Evidence that fimbriae of the smut fungus Microbotryum violaceum contain RNA.
AB  - The cells of the fungus Microbotryum violaceum produce many long, fine surface
      hairs that are similar in size and morphology to bacterial pili or fimbriae.
      These fungal fimbriae are assembled from 74 kDa glycoprotein subunits. We now
      present evidence that these fimbriae also have a RNA component. Isopycnic
      centrifugation of fimbriae in caesium chloride produced one band at a density
      intermediate to that of protein and nucleic acid. The absorbance spectrum of the
      intact fimbriae was consistent with that of a nucleoprotein. After extraneous
      RNAs were enzymically removed from the purified fimbrial preparation, disruption
      of the fibrils resulted in the release of not only the 74 kDa glycoprotein
      subunits, but also a 30 base single-stranded RNA species. To our knowledge, this
      is the first example of extracellular RNA as a component of a surface appendage.

PMID- 7528082
TI  - Cloning and nucleotide sequence analysis of pepV, a carnosinase gene from
      Lactobacillus delbrueckii subsp. lactis DSM 7290, and partial characterization of
      the enzyme.
AB  - Cell extracts of Lactobacillus delbrueckii subsp. lactis DSM 7290 were found to
      exhibit unique peptolytic ability against unusual beta-alanyl-dipeptides. In
      order to clone the gene encoding this activity, designated pepV, a gene library
      of strain DSM 7290 genomic DNA, prepared in the low-copy-number plasmid pLG339,
      was screened for heterologous expression in Escherichia coli. Recombinant clones
      harbouring pepV were identified by their ability to allow the utilization of
      carnosine (beta-alanyl-histidine) as a source of histidine by the E. coli mutant
      strain UK197 (pepD, hisG). Complementation was observed in a colony harbouring a
      recombinant plasmid (pKV101), carrying pepV. A 2.4 kb fragment containing pepV
      was subcloned and its nucleotide sequence revealed an open reading frame (ORF) of
      1413 nucleotides, corresponding to a protein with predicted molecular mass of
      51998 Da. A single transcription initiation site 71 bp upstream of the ATG
      translational start codon was identified by primer extension. No significant
      homology was detected between pepV or its deduced amino acid sequence with any
      entry in the databases. The only similarity was found in a region conserved in
      the ArgE/DapE/CPG2/YscS family of proteins. This observation, and protease
      inhibitor studies, indicated that pepV is of the metalloprotease type. A second
      ORF present in the sequenced fragment showed extensive homology to a variety of
      amino acid permeases from E. coli and Saccharomyces cerevisiae.

PMID- 7528080
TI  - Serum levels of c-erbB-2 protein in digestive diseases.
AB  - The clinical significance of the measurement of c-erbB-2 oncogene product was
      evaluated. The subjects consisted of 404 patients, including 248 with cancer of
      the digestive organs and 128 with benign digestive diseases. Serum c-erbB-2
      protein levels were measured by sandwich immunoenzyme assay. The positive rates
      of c-erbB-2 protein, at a cut-off value of 17.0 U/ml, were, for cancers:
      hepatocellular carcinoma 61.6%, biliary tract cancer 54.8%, pancreatic cancer
      25.0%, esophageal cancer 33.3%, gastric cancer 16.9%, and colorectal cancer 5.0%.
      For benign digestive diseases, the rates were: liver cirrhosis 63.3%, chronic
      hepatitis 43.2%, acute hepatitis 42.9%, other liver diseases 42.8%,
      cholelithiasis 30.0%, and chronic pancreatitis 0%. Serum c-erbB-2 protein levels
      were significantly correlated with the markers of hepatic functional reserve, the
      indocyanine green retention rate and the hepaplastin test. These findings suggest
      that serum c-erbB-2 protein levels are greatly influenced by liver dysfunction
      and that their clinical usefulness as a serum tumor marker is questionable.

PMID- 7528084
TI  - Acetylcholinesterase-containing intrinsic neurons in the rat main olfactory bulb:
      cytological and neurochemical features.
AB  - Acetylcholinesterase (AChE) histochemistry in light and electron microscopy was
      used to identify cholinoceptive neurons in the olfactory bulb of adult and 15-day
      old rats. Double-labelling experiments using AChE histochemistry and either
      tyrosine hydroxylase or GABA immunocytochemistry with light microscopy were also
      performed in order to specify the chemical nature of cholinoceptive neurons.
      Superficial short-axon cells and several morphological subtypes of deep short
      axon cells (second-order interneurons) are the most numerous AChE-containing
      intrinsic neurons in the olfactory bulb. Short-axon interneurons seem to be the
      only neurons expressing AChE in the deep olfactory bulb since the numerous
      granule cells (first-order interneurons) were never found to be AChE-positive,
      even in electron microscopy. In the superficial olfactory bulb, cholinoceptive
      cells belong to several neuronal categories. In addition to the intensely
      labelled superficial short-axon cells, a few periglomerular cells (first-order
      interneurons) display weak but significant AChE expression, clearly visible in
      electron microscopy. Both ultrastructural and double-labelling observations
      support the hypothesis that a subset of superficial tufted cells is also
      cholinoceptive. The coexistence of AChE and tyrosine hydroxylase in large neurons
      located in the glomerular and superficial external plexiform layers indicates
      that some, if not all, cholinoceptive tufted cells belong to the dopaminergic
      population previously observed in this area. These observations indicate that
      several types of intrinsic neurons express AChE and can be tentatively considered
      as cholinoceptive. Our results provide an anatomical substrate for hypotheses
      concerning the complex effects of acetylcholine in the processing of sensory
      information in the olfactory bulb.

PMID- 7528086
TI  - [Tubeless methods of the assessment of functional state of digestive organs in
      hormonal disorders].
AB  - The function of the stomach, pancreas, and intestine was studied in patients with
      chronic duodenitis without resorting to intubation. Disordered relationships
      between the hormones participating in the functioning of the hypophyseo-antral
      and entero-thyroid axis, resulting in trophic disorders in the gastroduodenal
      zone, are associated with characteristic shifts shown by methods of investigation
      other than intubation: drastically increased acid production in the presence of
      unchanged activity of urinary amylase before and after nutrient stimulation,
      combined with amylasorrhea. Diagnostic methods without intubation can earlier
      detect gastroduodenal diseases of dyshormonal etiology, particularly in children.
      Such methods may be used for initial screening, preceding more profound studies
      of both the hormonal status and the function of the organs of digestion.

PMID- 7528087
TI  - FK506 and deoxyspergualin: experimental studies and clinical applications.

PMID- 7528088
TI  - Particular phenotypic profile of blood lymphocytes during obliterative
      bronchiolitis syndrome following lung transplantation.
AB  - Bronchiolitis obliterans syndrome (OBS) remains the major complication in long
      term survivors with heart-lung transplants, occurring in up to 50% of patients
      who survived the first year postsurgery. Until now, a significant decrease in
      small airway flow parameters has represented the most sensitive index for the
      detection of early OBS. Using immunocytofluorometric analysis, in a prospective
      study we have analysed the phenotype of peripheral blood lymphocyte effector and
      regulatory subsets in seven patients with inactive well-established OBS as
      compared with lung transplant recipients without any complication. We found a
      particular phenotypic profile during well-established OBS characterized by: (1)
      the disappearance of the CD19+ B cell population despite normal or increased
      immunoglobulin blood levels; (2) a marked decrease in the CD4+/CD8+ ratio; (3) a
      dramatic increase in phenotypic cytotoxic effector T cells CD8+S6F1+high and
      CD3+CD4-CD8-; (4) a dramatic increase in the CD4+CD29+/CD4+CD45RA+ ratio
      associated with the loss of the phenotypic suppressor/inducer CD4+CD45RA+T cells.
      The results of this preliminary study suggest that, using this selected
      combination of lymphocyte membrane markers, sequential phenotyping could be
      useful in the noninvasive follow-up of lung transplant recipients. The predictive
      value of this phenotypic profile for the early diagnosis of OBS is under
      investigation.

PMID- 7528085
TI  - Correlation of blood levels of soluble vascular cell adhesion molecule-1 with
      disease activity in systemic lupus erythematosus and vasculitis.
AB  - Levels of soluble adhesion molecules have been shown to reflect their cell
      surface expression in vitro, and thus may provide a useful surrogate marker of
      surface expression at inflammatory sites. In patients with SLE and vasculitis,
      serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell
      adhesion molecule-1 (VCAM-1) and E-Selection were determined by ELISA during
      different stages of disease activity. Levels of soluble(s) VCAM-1 correlated with
      disease activity in patients with SLE, being significantly higher during active
      compared with inactive disease (P = 0.003), and normalizing with clinical
      remission. By contrast, in patients with vasculitis, although sVCAM-1 levels were
      elevated in active disease, they fell but did not normalize in inactive disease,
      suggesting that treatment may be suppressing the clinical manifestations rather
      than targeting the underlying pathogenic mechanism. Soluble ICAM-1 and E-Selectin
      levels did not relfect disease activity in either SLE or vasculitis.

PMID- 7528090
TI  - Munchausen syndrome by proxy: unusual manifestations and disturbing sequelae.
AB  - Since the initial description of Munchausen Syndrome by Proxy (MSBP) (Meadow,
      1977), numerous cases have been reported varying from as simple as the complaint
      of a nonexistent symptom to those as complicated as altered laboratory tests
      leading to the false diagnosis of cystic fibrosis (Orenstein & Wasserman, 1986;
      Rosenberg, 1987). We report three findings previously unreported: esophageal
      perforation, retrograde intussusception, and tooth loss. Bradycardia has been
      previously reported associated with suffocation (Meadow, 1984), but in our case
      may have been caused by carotid artery massage. We also suggest possible
      induction by the mother of premature rupture of fetal membrane leading to
      delivery of infected infants.

PMID- 7528089
TI  - Twisted alpha-keto amides as transition-state analogues for acyl-transfer
      reactions: synthesis of the immunoconjugates.
AB  - Two new haptens were employed as antigens to elicit antibodies for acyl-transfer
      reactions. The haptens, both alpha-keto amides were designed to elicit antibodies
      which could twist potential substrates into a much more reactive conformation.
      The rationale for their design, synthesis, and immunization protocols will be
      discussed.

PMID- 7528092
TI  - Detection of naturally occurring enteroviruses and hepatitis A virus in
      undigested and anaerobically digested sludge using the polymerase chain reaction.
AB  - Four undigested and four anaerobically digested sewage sludge samples were
      analyzed for enteroviruses and hepatitis A virus using seminested and double
      polymerase chain reaction (PCR), respectively. For enteroviruses, all eight
      samples were positive when detection was by seminested PCR. Using cell culture
      all samples except two digested sludge samples were positive. For hepatitis A
      virus, seven out of eight samples were positive by PCR detection. In all samples,
      PCR inhibitory substances were removed by passage through Sephadex G-50 and
      Chelex 100 columns. Overall the PCR methodology was highly successful in
      identifying the presence of both viruses; however, with this methodology, there
      was no indication as to whether enteroviruses or hepatitis A viruses not
      confirmed in cell culture were infectious.

PMID- 7528091
TI  - Pneumatosis intestinalis. Appearance on MR examination.
AB  - We describe the magnetic resonance (MR) appearance of pneumatosis intestinalis in
      two patients. Pneumatosis is suggested by the finding of circumferential
      collections of air adherent or within the bowel wall. This air is more apparent
      on gradient-echo images due to "blooming" associated with magnetic field
      inhomogeneities at air-tissue interfaces. While MR is not routinely indicated as
      a diagnostic tool for the detection of pneumatosis, the radiologist should
      nevertheless be familiar with its appearance on MR examination.

PMID- 7528093
TI  - Structure of the putative O10 antigen from Acinetobacter baumannii.
AB  - A polysaccharide containing L-rhamnose, 2-acetamido-2-deoxy-D-glucose, and 2
      acetamido-2-deoxy-D-mannose was obtained from an aqueous phenol extract of
      isolated cell walls from the reference strain for Acinetobacter baumannii
      serogroup O10. By means of NMR studies and chemical degradations, the repeating
      unit of the polymer (the putative O10 antigen) was identified as a branched
      pentasaccharide of the structure shown.

PMID- 7528094
TI  - Unprimed CD4+ and CD8+ T cells can be rapidly activated by a CD3 x CD19
      bispecific antibody to proliferate and become cytotoxic.
AB  - We previously reported that a CD3 x CD19 bispecific antibody (bsAb) can induce
      efficient killing of tumour cells by preactivated T cells isolated from patients
      with B cell malignancy. For future intravenous application we investigated
      whether resting T cells from peripheral blood can be stimulated to proliferate
      and become cytotoxic with the CD3 x CD19 bsAb alone. Indeed peripheral blood
      mononuclear cells, isolated from healthy donors or patients with B cell
      malignancy, started to proliferate within 1 day in response to CD3 x CD19 bsAb.
      Within the same time span cytotoxic activity against CD19-positive tumour cells
      was already detectable. Maintenance of cytotoxic activity was seen during 3 days
      of culture but optimal lysis of the target cells then required fresh CD3 x CD19
      bsAb in the cytotoxicity assay. Essentially the same results for proliferation
      and cytotoxicity were found when separated CD4-positive and CD8-positive T cells
      were activated by the bsAb in the presence of autologous monocytes. These results
      may be relevant for the in vivo application of the bsAb when used as
      immunotherapy in patients with B cell malignancy.

PMID- 7528095
TI  - Lateral septal projections onto tubero-infundibular neurons in the hypothalamus
      of the guinea pig.
AB  - Efferent projections of the lateral septal nucleus (LS) to the preoptic area and
      the hypothalamus were identified in 20 female guinea pigs after iontophoretic
      injection of the anterograde axonal tracer Fluoro-Ruby. Tubero-infundibular (TI)
      neurons of the preoptic area and the hypothalamus were retrogradely labeled after
      intracardiac injection of Granular Blue or Fluoro-Gold. Magnocellular neurons of
      the supraoptic and paraventricular nuclei were also labeled. The double labeling
      procedure allowed an estimation of the extent of the direct relationship between
      LS efferents and TI neurons. Contacts between lateral septal fibers and TI cell
      bodies were mainly observed at the light-microscopical level in the preoptic
      area. A group of labeled fibers coursing along the third ventricle established
      sparse connections with hypothalamic periventricular TI neurons. A few
      appositions was observed in the infundibular (arcuate) nucleus, suggestive of a
      monosynaptic regulation of TI neurons by a septo-arcuate tract. Close association
      with labeled magnocellular neurons was also noted at the edge of the supraoptic
      and paraventricular nuclei. The sparse but direct connections between LS and TI
      neurons may be involved in the neuroendocrine functions of the LS.

PMID- 7528096
TI  - Co-localization of nitric oxide synthase and vasoactive intestinal peptide
      immunoreactivity in neurons of the major pelvic ganglion projecting to the rat
      rectum and penis.
AB  - Nitric oxide synthase (NOS)- and vasoactive intestinal peptide (VIP)
      immunoreactive neurons projecting to the upper rectum or penis were examined
      using retrograde tracing combined with immunohistochemistry in the major pelvic
      ganglion of male rats. Five days after injection of Fluoro-Gold (FG) into the
      upper rectum or penis, the major pelvic ganglion was treated with colchicine. FG
      injected into the upper rectum labelled many ganglion neurons in the major pelvic
      ganglion. Immunohistochemistry showed that 37% of FG-labelled neurons were
      immunoreactive for NOS and 33% for VIP. After injection of FG into the penis, 41%
      of FG-labelled neurons were immunoreactive for NOS and 25% for VIP. Serial
      cryostat sections stained for NOS and VIP, respectively, showed the co
      localization of NOS and VIP in the ganglion cells projecting to the rectum and
      penis. In the major pelvic ganglion of the colchicine-treated animals, about 17%
      of the ganglion cells were immunoreactive for NOS and 32% were immunoreactive for
      VIP. These neurons were small in diameter (less than 30 microns). A histogram
      showing cell sizes in cross-sectional areas of NOS-immunoreactive neurons
      coincided with that of VIP-immunoreactive neurons. Most of the NOS- and VIP
      immunoreactive neurons were less than 600 microns. These results indicate that
      small neurons containing both NOS and VIP in the major pelvic ganglion project to
      the rectum and penis. In the penile erectile tissues and enteric ganglia, NO and
      VIP may be released from the same axons and may act concomitantly on the target
      tissue.

PMID- 7528097
TI  - Immunohistochemical localization of serine-protease inhibitors in the human
      placenta.
AB  - Proteases and their inhibitors play a pivotal role in developmental and
      differentiative processes. In the present report we investigated the
      immunohistochemical localization of alpha 1-antitrypsin, alpha 1-antichymotrypsin
      and inter-alpha-trypsin inhibitor in first trimester as well as in term human
      placentas. For this purpose polyclonal antibodies against these serine-protease
      inhibitors were used. All inhibitors were expressed in the villous
      syncytiotrophoblast of first and last trimester placentas. Placental fibrinoid
      was positively stained for alpha 1-antitrypsin and inter-alpha-trypsin inhibitor
      throughout gestation. alpha 1-Antitrypsin and alpha 1-antichymotrypsin showed a
      strong immunostaining in the Hofbauer cells (first trimester and full term
      placentas). Extravillous cytotrophoblast was negative for the three protease
      inhibitors throughout gestation. The presence of the three inhibitors in the
      syncytiotrophoblast suggests a role in coagulative, invasive and immunomodulatory
      processes. Fibrinoid, staining for alpha 1-antitrypsin and inter-alpha-trypsin
      inhibitor, could also have an important immunoprotective function. The presence
      of protease inhibitors in the Hofbauer cells suggests an involvement of these
      cells in villous remodelling and differentiative processes.

PMID- 7528099
TI  - Descending neurons with dopamine-like or with substance P/FMRFamide-like
      immunoreactivity target the somata of olfactory interneurons in the brain of the
      spiny lobster, Panulirus argus.
AB  - Two sets of descending neurons primarily target the somata of neurons in the
      olfactory deutocerebrum of the spiny lobster, Panulirus argus. Hundreds to
      thousands of dopamine-like immunoreactive fibers originate in the lateral
      protocerebrum and terminate among the clustered somata of the olfactory
      deutocerebrum projection neurons (lateral soma cluster) and those of the
      olfactory deutocerebrum local interneurons (medial soma cluster). A pair of giant
      neurons with substance P- and FMRFamide-like immunoreactivity from the median
      protocerebrum terminate primarily in the lateral soma cluster, but also branch in
      the core of the olfactory lobe itself. Neurons of both types terminate in
      numerous bouton-like swellings. The terminals in the lateral cluster at least
      contain numerous, large, dense-core and small, clear vesicles. The terminals
      contact the somata and the primary neurites through both traditional chemical
      synapses and large zones of direct membrane appositions. In most instances, a
      vesicle-containing profile forms a triadic arrangement with a neurite and a soma
      the latter being frequently connected via large gap-junction-like structures.
      Rosette-like arrangements formed by a vesicle-containing profile surrounded by up
      to eight neurites are also common. Dissociated lateral cluster somata support
      both fast inward and sustained outward voltage-activated currents. Substance P,
      but not dopamine or FMRFamide-related peptides, alters the fast inward current.
      The somata of the olfactory projection neurons, and possibly those of the
      olfactory local interneurons, appear to serve an integrative, and not merely a
      supportive role in these invertebrate central neurons.

PMID- 7528098
TI  - Differential localization of neuronal nitric oxide synthase immunoreactivity and
      NADPH-diaphorase activity in the cat spinal cord.
AB  - The distributions of neuronal nitric oxide synthase immunoreactivity (NOS-IR) and
      NADPH-diaphorase (NADPH-d) activity were compared in the cat spinal cord. NOS-IR
      in neurons around the central canal, in superficial laminae (I and II) of the
      dorsal horn, in the dorsal commissure, and in fibers in the superficial dorsal
      horn was observed at all levels of the spinal cord. In these regions, NOS-IR
      paralleled NADPH-d activity. The sympathetic autonomic nucleus in the rostral
      lumbar and thoracic segments exhibited prominent NOS-IR and NADPH-d activity,
      whereas the parasympathetic nucleus in the sacral segments did not exhibit NOS-IR
      or NADPH-d activity. Within the region of the sympathetic autonomic nucleus,
      fewer NOS-IR cells were identified compared with NADPH-d cells. The most
      prominent NADPH-d activity in the sacral segments occurred in fibers within and
      extending from Lissauer's tract in laminae I and V along the lateral edge of the
      dorsal horn to the region of the sacral parasympathetic nucleus. These afferent
      projections did not exhibit NOS-IR; however, NOS-IR and NADPH-d activity were
      demonstrated in dorsal root ganglion cells (L7-S2). The results of this study
      demonstrate that NADPH-d activity is not always a specific histochemical marker
      for NO-containing neural structures.

PMID- 7528100
TI  - Three-dimensional architecture of the tubular endocytic apparatus and
      paramembranous networks of the endoplasmic reticulum in the rat visceral yolk-sac
      endoderm.
AB  - The three-dimensional architecture of the tubular endocytic apparatus and the
      endoplasmic reticulum in the rat yolk-sac endoderm was investigated after loading
      with horseradish peroxidase-conjugated concanavalin A by intrauterine
      administration. After 30 min, small vesicles (50-150 nm in diameter), small
      tubules (80-100 nm in diameter) and large vacuoles (0.2-1.0 microns in diameter)
      in the apical cytoplasm were labeled with the tracer, but lysosomes (1.0-3.5
      microns in diameter) in the supranuclear cytoplasm were not labeled until 60 min
      after loading. Stereo-viewing of the labeled small tubules in thick sections
      revealed that they were not isolated structures but formed three-dimensional
      anastomosing networks, which were also confirmed by scanning electron microscopy
      after maceration with diluted osmium tetroxide. Their earlier labeling with the
      endocytic tracer, localization in the apical cytoplasm and three-dimensional
      network formation indicated that the labeled small tubules represented tubular
      endosomes (tubular endocytic apparatus). These well-developed membranous networks
      provided by the tubular endosomes are suggested to facilitate the receptor
      mediated endocytosis and transcytosis of the maternal immunoglobulin in the rat
      yolk-sac endoderm. Scanning electron microscopy further revealed lace-like
      networks of the smooth endoplasmic reticulum near the lateral plasma membrane.
      Their possible involvement in transport of small molecules or electrolytes is
      discussed.

PMID- 7528101
TI  - Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal
      mesoderm induction in early Xenopus embryos.
AB  - The cadherin-catenin complex has an important role in cell-cell adhesion and may
      also function in signaling pathways. We report that overexpression of three
      cadherin types in Xenopus embryos causes them to develop with reduced dorsal
      axial structures. The same phenotype is produced in embryos that have been
      depleted of maternal beta-catenin protein by an antisense oligodeoxynucleotide
      complementary to beta-catenin mRNA. They show an inhibition in the expression of
      dorsal mesodermal markers MyoD and goosecoid, but not of ventral and general
      mesodermal markers. They lack notochords, somites, and neural tubes and are
      defective in dorsal mesodermal signaling in Nieuwkoop assays. The phenotype can
      be rescued by the injection of beta-catenin mRNA and not by the injection of Xwnt
      8 mRNA. These results show that beta-catenin has an important role in dorsal
      mesoderm induction. They directly demonstrate the activity of a maternal mRNA in
      axis specification.

PMID- 7528102
TI  - Perlecan, basal lamina proteoglycan, promotes basic fibroblast growth factor
      receptor binding, mitogenesis, and angiogenesis.
AB  - A survey of defined species of cell surface and extracellular matrix heparan
      sulfate proteoglycans (HSPG) was performed in a search for cellular proteoglycans
      that can promote bFGF receptor binding and biological activity. Of the various
      affinity-purified HSPGs tested, perlecan, the large basement membrane HSPG, is
      found to induce high affinity binding of bFGF both to cells deficient in HS and
      to soluble FGF receptors. Heparin-dependent mitogenic activity of bFGF is
      strongly augmented by perlecan. Monoclonal antibodies to perlecan extract the
      receptor binding promoting activity from active HSPG preparations. In a rabbit
      ear model for in vivo angiogenesis, perlecan is a potent inducer of bFGF-mediated
      neovascularization. These results identify perlecan as a major candidate for a
      bFGF low affinity, accessory receptor and an angiogenic modulator.

PMID- 7528103
TI  - Heparin-induced oligomerization of FGF molecules is responsible for FGF receptor
      dimerization, activation, and cell proliferation.
AB  - Heparin is required for fibroblast growth factor (FGF) stimulation of biological
      responses. Using isothermal titration calorimetry, we show that acidic FGF (aFGF)
      forms a 1:1 complex with the soluble extracellular domain of FGF receptor (FGFR).
      Heparin exerts its effect by binding to many molecules of aFGF. The resulting
      aFGF-heparin complex can bind to several receptor molecules, leading to FGFR
      dimerization. In two cell lines lacking endogenous heparan sulfate, exogenous
      heparin is required for FGFR dimerization, tyrosine kinase activation, c-fos mRNA
      transcription, and cell proliferation. Moreover, a synthetic heparin analog that
      binds monovalently to aFGF blocks FGFR dimerization, activation, and signaling
      via FGFR. We propose that heparin causes oligomerization of aFGF such that its
      binding to FGFR results in dimerization and activation. This represents a novel
      mechanism for transmembrane signaling and may account for the action of many
      heparin-bound growth factors.

PMID- 7528104
TI  - RecA homologs Dmc1 and Rad51 interact to form multiple nuclear complexes prior to
      meiotic chromosome synapsis.
AB  - Dmc1 and Rad51, yeast homologs of the E. coli RecA protein, are shown by
      immunostaining to localize to as many as 64 sites within spread meiotic nuclei.
      Genetic requirements for this punctate pattern suggest it represents
      recombination intermediates. Dmc1 and Rad51 colocalize and are therefore likely
      to act together during recombination. Despite their similarities, the two
      proteins have specialized functions: Dmc1 complexes do not form in rad51 mutants,
      while Rad51 complexes are retained indefinitely in dmc1 mutants. Dmc1 and, by
      inference, Rad51 form complexes before synapsis as monitored by immunostaining
      for Zip1 protein. Analysis of zip1 mutants shows that Zip1 promotes dissociation
      of Dmc1 complexes. Colocalization of Dmc1 and Zip1 raises the possibility that
      Dmc1 and Rad51 are components of recombination nodules.

PMID- 7528105
TI  - Topographic organization of embryonic motor neurons defined by expression of LIM
      homeobox genes.
AB  - Motor neurons located at different positions in the embryonic spinal cord
      innervate distinct targets in the periphery, establishing a topographic neural
      map. The topographic organization of motor projections depends on the generation
      of subclasses of motor neurons that select specific paths to their targets. We
      have cloned a family of LIM homeobox genes in chick and show here that the
      combinatorial expression of four of these genes, Islet-1, Islet-2, Lim-1, and Lim
      3, defines subclasses of motor neurons that segregate into columns in the spinal
      cord and select distinct axonal pathways. These genes are expressed prior to the
      formation of distinct motor axon pathways and before motor columns appear. Our
      results suggest that LIM homeobox genes contribute to the generation of motor
      neuron diversity and may confer subclasses of motor neurons with the ability to
      select specific axon pathways, thereby initiating the topographic organization of
      motor projections.

PMID- 7528106
TI  - Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr
      virus reactivation.
AB  - Nitric oxide (NO) produced by murine macrophages is important in murine
      resistance to ectromelia virus, herpes simplex virus, and vaccinia virus
      infection. In contrast, NO production by human mononuclear cells has been
      difficult to demonstrate, and a role for NO in human responses to infection is
      uncertain. We report constitutive, low level, macrophage-type NO synthase (iNOS)
      expression in Epstein-Barr virus (EBV)-transformed human B lymphocytes and
      Burkitt's lymphoma cell lines. Immune NOS activity is involved in maintaining EBV
      latency through down-regulation of the expression of the immediate-early EBV
      transactivator Zta. NO also inhibits apoptosis in B lymphocyte cell lines. The
      effects of NO are largely independent of cGMP and influential on signaling
      pathways regulated by (sulfhydryl) redox status. These results suggest that NO
      plays a physiological role in human B cell biology by inhibiting programmed cell
      death and maintaining viral latency.

PMID- 7528107
TI  - Integrin alpha v beta 3 antagonists promote tumor regression by inducing
      apoptosis of angiogenic blood vessels.
AB  - A single intravascular injection of a cyclic peptide or monoclonal antibody
      antagonist of integrin alpha v beta 3 disrupts ongoing angiogenesis on the chick
      chorioallantoic membrane (CAM). This leads to the rapid regression of
      histologically distinct human tumors transplanted onto the CAM. Induction of
      angiogenesis by a tumor or cytokine promotes vascular cell entry into the cell
      cycle and expression of integrin alpha v beta 3. After angiogenesis is initiated,
      antagonists of this integrin induce apoptosis of the proliferative angiogenic
      vascular cells, leaving preexisting quiescent blood vessels unaffected. We
      demonstrate therefore that ligation of integrin alpha v beta 3 is required for
      the survival and maturation of newly forming blood vessels, an event essential
      for the proliferation of tumors.

PMID- 7528108
TI  - KIF1B, a novel microtubule plus end-directed monomeric motor protein for
      transport of mitochondria.
AB  - To further elucidate the mechanism of organelle transport, we cloned a novel
      member of the mouse kinesin superfamily, KIF1B. This N-terminal-type motor
      protein is expressed ubiquitously in various kinds of tissues. In situ
      hybridization revealed that KIF1B is expressed abundantly in differentiated nerve
      cells. Interestingly, K1F1B works as a monomer, having a microtubule plus end
      directed motility. Our rotary shadowing electron microscopy revealed mostly
      single globular structures. Immunocytochemically, KIF1B was colocalized with
      mitochondria in vivo. Furthermore, a subcellular fractionation study showed that
      KIF1B was concentrated in the mitochondrial fraction, and purified K1F1B could
      transport mitochondria along microtubules in vitro. These data strongly suggested
      that KIF1B works as a monomeric motor for anterograde transport of mitochondria.

PMID- 7528109
TI  - Information coding in the olfactory system: evidence for a stereotyped and highly
      organized epitope map in the olfactory bulb.
AB  - In the mammalian olfactory system, information from approximately 1000 different
      odorant receptor types is organized in the nose into four spatial zones. Each
      zone is a mosaic of randomly distributed neurons expressing different receptor
      types. In these studies, we have obtained evidence that information highly
      distributed in the nose is transformed in the olfactory bulb of the brain into a
      highly organized spatial map. We find that specific odorant receptor gene probes
      hybridize in situ to small, and distinct, subsets of olfactory bulb glomeruli.
      The spatial and numerical characteristics of the patterns of hybridization that
      we observe with different receptor probes indicate that, in the olfactory bulb,
      olfactory information undergoes a remarkable organization into a fine, and
      perhaps stereotyped, spatial map. In our view, this map is in essence an epitope
      map, whose approximately 1000 distinct components are used in a multitude of
      different combinations to discriminate a vast array of different odors.

PMID- 7528110
TI  - [Adenocarcinoma in Barrett's esophagus: long-term results of curative resection].
AB  - Between 1980 and 1993, out of 635 patients presenting with an adenocarcinoma of
      the esophagogastric junction, 74 (11.7%) had a neoplasm arising from a columnar
      specialized epithelium lining the distal esophagus. Fifty of these patients (68%)
      underwent a curative (R0) resection. 36 patients (72%) were in stage 0, I or II,
      and the 5-year actuarial survival rate was 44%. The survival rate dropped to 13%
      when nodal metastases were present. We conclude that the long-lasting symptoms
      during the pre-neoplastic phase, and a closer endoscopic surveillance allow a
      early diagnosis of Barrett adenocarcinoma. Surgical therapy must be radical in
      these patients in order to improve prognosis.

PMID- 7528111
TI  - Effects of complete and incomplete tumor promoters on hair growth, angiogenesis,
      and tenascin expression in the skin of NMRI mice.
AB  - Although the phorbol esters 12-O-tetradecanoylphorbol-13-acetate (TPA) and 12-O
      retinoylphorbol-13-acetate (RPA) are almost equipotent inducers of an
      inflammatory and hyperplastic response in NMRI mouse skin, TPA acts as a
      converting or complete and RPA as a non-converting or incomplete skin tumor
      promoter. Bearing in mind the converting effect of skin wounding and TGF beta, we
      have addressed the question of a relationship between conversion and stromal
      events. For this purpose we have compared the effects of TPA and RPA on dermal
      angiogenesis, hair regrowth and the expression of tenascin in NMRI mouse skin in
      vivo. In the reticular part of the dermis, shaving alone induced angiogenesis
      peaking at day 14, concomitant with hair regrowth. While TPA exhibited a
      stimulatory effect on both parameters, RPA suppressed shaving-induced
      angiogenesis and delayed the onset of hair regrowth. Whether this difference in
      the phorbol ester effects being consistent with the working hypothesis is
      critical for conversion, remains to be shown. In the papillary dermis, however,
      RPA was more potent than TPA in inducing vascularization and tenascin expression.
      The kinetics of both responses corresponded to the time course of
      hyperproliferation induced by the phorbol esters in the overlaying epidermis,
      i.e. may be related to promotion proper, rather than conversion.

PMID- 7528112
TI  - Microvascular responses to inhibition of nitric oxide production. Role of active
      oxidants.
AB  - The objective of this study was to assess the potential contribution of hydrogen
      peroxide (H2O2) to the leukocyte-endothelial cell adhesion and increased
      microvascular permeability observed in rat mesenteric venules after inhibition of
      nitric oxide synthesis with NG-nitro-L-arginine methyl ester (L-NAME). Leukocyte
      adherence and emigration and leakage of fluorescein isothiocyanate-labeled
      albumin were monitored in postcapillary venules before and after exposure of the
      tissue to L-NAME. H2O2 production in mesenteric tissue was monitored by using
      dihydrorhodamine 123 (DHR), the H2O2-sensitive fluorochrome. L-NAME elicited a
      rapid increase in both the rate of albumin extravasation and oxidation of DHR,
      which was followed by an increased adherence and emigration of leukocytes in
      postcapillary venules. Treatment with either catalase or dimethylthiourea
      attenuated the L-NAME-induced oxidative stress, albumin leakage, and leukocyte
      endothelial cell adhesion. Oxidation of DHR was enhanced in animals treated with
      either 3-amino-1,2,4-triazole (ATZ), an inhibitor of endogenous catalase, or a
      combination of ATZ and maleic acid diethyl ester, which depletes intracellular
      glutathione. Animals receiving a CD11/CD18-specific antibody to prevent leukocyte
      adhesion/emigration exhibited a reduced oxidation of DHR in response to L-NAME.
      These findings indicate that most of the H2O2 (and secondarily derived oxidants)
      generated in mesenteric tissue exposed to an inhibitor of nitric oxide production
      is due to accumulation of activated leukocytes.

PMID- 7528113
TI  - Biochemical diagnosis in prenatal uropathy.
AB  - Thirty-two fetuses, six with prune-belly syndrome, seven with renal cyst, 19 with
      obstructive uropathy, underwent intrauterine fluid aspiration during weeks 15-37
      of gestation. Fluid samples were analysed for Na, K, creatinine, urea, alpha 1-,
      and beta 2-microglobulin. Aspirate concentrations of sodium below 130 mmol/L and
      creatinine above 115 mumol/L indicate an active kidney and exclude a renal cyst.
      However, aspirates from fetal cysts or fetuses with obstructive uropathy showed
      analyte concentrations for sodium, potassium, creatinine, and urea corresponding
      to extracellular fluid (ECF). In conclusion fluid aspirates of fetuses with
      ultrasonographically detectable cystic cavities in the abdomen should be examined
      for sodium and creatinine to assess remaining renal function for planning of
      obstetric management.

PMID- 7528114
TI  - Are referrals to developmental pediatricians appropriate? Our experience over a
      15-year period.

PMID- 7528115
TI  - Colloid infusion after brain injury: effect on intracranial pressure, cerebral
      blood flow, and oxygen delivery.
AB  - OBJECTIVES: We sought to determine the effects of colloid osmotic pressure on
      cerebral edema formation after brain injury. We hypothesized that an increase in
      plasma oncotic pressure accompanying a colloid infusion would be associated with
      a decrease in intracranial pressure and increases in cerebral blood flow and
      oxygen delivery when compared with isotonic crystalloid. DESIGN: Prospective,
      laboratory study. SETTING: University surgical research laboratory. SUBJECTS:
      Adult swine, both genders. INTERVENTIONS: Cryogenic brain injury with intravenous
      fluid infusion of either lactated Ringer's solution or 6% dextran-70 in normal
      saline. The effect of this intervention was monitored for 24 hrs. MEASUREMENTS:
      Mean arterial pressure, central venous pressure, intracranial pressure,
      hemoglobin concentration, plasma oncotic pressure, serum osmolality, cerebral
      blood flow, and specific gravity of cortical biopsies. RESULTS: Cryogenic injury
      significantly increased the cortical water content and the intracranial pressure
      and significantly decreased the cerebral blood flow and oxygen delivery (p <
      .05). Dextran infusion significantly increased the colloid oncotic pressure.
      There were no differences between the lactated Ringer's solution and dextran
      groups in intracranial pressure, cerebral oxygen delivery, or cortical water
      content after 24 hrs. CONCLUSIONS: Colloid infusion after a focal cryogenic
      injury does not increase cerebral oxygen delivery or reduce either cerebral edema
      formation or intracranial pressure when compared with lactated Ringer's solution.
      Colloid is not superior to isotonic crystalloid in the management of isolated
      brain injury.

PMID- 7528116
TI  - Analysis of thromboxane receptor-mediated responses in the feline pulmonary
      vascular bed.
AB  - OBJECTIVE: Current evidence suggests that thromboxane plays a role in
      pathophysiologic processes in the lung. Efforts to find effective, specific
      therapy to modify these effects have led to the development of a new class of
      thromboxane receptor blockers. This present investigation examined the
      selectivity and duration of the inhibitory effects of one of these novel agents
      in the pulmonary vascular bed of anesthetized cats. DESIGN: Prospective,
      randomized, controlled study with repeated measures. SETTING: University research
      laboratory. SUBJECTS: Twenty-nine adult cats obtained from the Tulane University
      School of Medicine vivarium. INTERVENTIONS: The effects of GR32191, a thromboxane
      receptor antagonist, were investigated under constant-flow conditions in the
      intact-chest cat, using a triple-lumen, 6-Fr, balloon perfusion catheter that was
      placed by means of fluoroscopic guidance. Data were analyzed using a paired or
      unpaired t-test or analysis of variance. A p < .05 was considered statistically
      significant. MEASUREMENTS AND MAIN RESULTS: Aortic, left atrial, and left lobar
      arterial pressures were measured. After administration of GR32191 (0.25 and 1.0
      mg/kg iv), pulmonary vasoconstrictor responses to U46619, a thromboxane mimic,
      were significantly decreased. Blockade was overcome with higher doses of the
      thromboxane mimic. GR32191 was without significant effect on the responses to
      prostaglandin (PG) D2, PGF2 alpha, serotonin, the calcium-channel agonist BAY
      K8644, or norepinephrine. Additionally, GR32191 did not alter baseline vascular
      pressures. Responses to U46619 returned to 50% of control value 90 mins after
      administration of 0.25 mg/kg of U46619. Responses to GR32191 returned to 50% of
      control value 180 mins after administration of 1.0 mg/kg of GR32191. These data
      suggest that GR32191 selectively blocks thromboxane A2 receptor-mediated
      responses in a competitive and reversible manner in the pulmonary vascular bed of
      the cat. CONCLUSIONS: These results are consistent with the hypothesis that
      discrete thromboxane A2 receptors, unrelated to receptors activated by PGF2 alpha
      or PGD2, are present in the feline pulmonary vascular bed. Specific thromboxane
      receptor antagonists, such as GR32191, could be useful therapeutic agents in the
      treatment of pulmonary hypertensive and thromboembolic disorders.

PMID- 7528117
TI  - Near-patient measurements of methemoglobin, oxygen saturation, and total
      hemoglobin: evaluation of a new instrument for adult and neonatal intensive care.
AB  - OBJECTIVES: a) To evaluate the performance of a compact, new instrument that uses
      disposable cuvettes to measure total hemoglobin concentration, oxygen content,
      and the relative concentrations of oxy- and methemoglobin in 50-microL blood
      samples; b) to determine whether the instrument can be used for near-patient
      assessment of methemoglobinemia; and c) to ascertain whether problems commonly
      encountered in neonatal blood samples affect the instrument's performance.
      DESIGN: Prospective study, in which the test instrument was compared with a
      standard method. Samples of whole blood with and without bilirubin, fetal
      hemoglobin, and hemolysis were analyzed on the new (test) instrument and on a
      widely used cooximeter (OSM3 hemoximeter, Radiometer; reference instrument).
      SETTING: In vitro analyses of blood samples in clinical and university
      laboratories. MEASUREMENTS AND MAIN RESULTS: There was a close linear correlation
      between the methomoglobin measurements of the test instrument and those
      measurements of the reference instrument (slope = 0.989; r2 = .989). The average
      difference in mean assay values between the reference instrument and the test
      instrument was -0.59%, i.e., < 1% methemoglobin. Repeated measurements indicated
      the precision was 0.5% methemoglobin. Complete hemolysis of the sample reduced
      the methemoglobin reading by only 0.40%. Adding bilirubin (10 to 11 mg/dL [171 to
      188.1 mumol/L]), increased the methemoglobin reading by 0.23%, increased the
      oxyhemoglobin reading by 0.45%, and increased total hemoglobin by 0.21 g/dL.
      Fetal hemoglobin also had minimal effects on the readings. CONCLUSIONS: The test
      instrument is fast and easy to operate. No sample preparation or pipetting is
      required. To operate the instrument, the user simply connects a syringe
      containing the blood sample to one of the disposable cuvettes, injects 50 microL
      of blood into the cuvette, and inserts the cuvette into the instrument. The test
      instrument automatically detects the presence of the cuvette, analyzes the
      sample, and displays the results in < 10 secs. The findings in this study
      indicate that the test instrument has sufficient accuracy for near-patient
      testing in intensive care units. The errors introduced by hemolysis, fetal
      hemoglobin, and bilirubin were too small to be of clinical importance. Thus, the
      test instrument is essentially unaffected by complications commonly encountered
      in neonatal blood. The capacity of the test instrument to measure methemoglobin
      makes it particularly useful if inhaled nitric oxide therapy becomes a standard
      clinical practice.

PMID- 7528119
TI  - [Detection of serum antibody of hepatitis C virus in parturients and their
      newborns].
AB  - Detection of serum antibody of hepatitis C virus (anti-HCV) with ELISA kits was
      performed in 315 parturients and their newborns. The results indicated that some
      of the infants, born of mothers infected with HCV were also anti-HCV positive,
      and a high positive rate of abnormal maternal hepato-function harbored a markedly
      positive rate of anti-HCV both in mother and newborn and bore a positive
      correlation to the maternal age. These suggest that besides the five routine
      tests, anti-HCV should better be determined, especially in mothers with abnormal
      hepato-function. If possible, in such cases HCV-RNA should be examined by using
      revert nested polymerase chain reaction technique to determine whether a vertical
      mother-infant transmission exists.

PMID- 7528118
TI  - Prognostic value of assessing contact system activation and factor V in systemic
      inflammatory response syndrome.
AB  - OBJECTIVE: To test if serially sampled determinations of the contact system
      proteins and factor V have prognostic value for death in patients who develop the
      systemic inflammatory response syndrome. DESIGN: Prospective, observational study
      with sequential measurements in an inception cohort. SETTING: Medical intensive
      care unit (ICU) in a community hospital. PATIENTS: Over a 1-yr period, a
      population base sample of 23 patients was selected from all ICU admissions who
      met established criteria for the systemic inflammatory response syndrome.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Components of the contact
      system, factor XII, prekallikrein, high-molecular-weight kininogen, factor XI,
      alpha 2-macroglobulin-kallikrein complexes and factor V values were measured in
      plasma samples collected serially (day of admission, and at 2, 12, 24, 48 and/or
      72 hrs or at discharge). Data were analyzed to determine if admission values or
      serially obtained values within 48 hrs were useful in predicting outcome.
      Fourteen patients survived and nine died. At admission, in all patients, assay
      values indicated that prekallikrein, high-molecular-weight kininogen, and factor
      V were significantly lower than normal (as observed in a range of 20 to 23
      healthy adults), alpha 2-macroglobulin-kallikrein complexes were higher than
      normal, while concentrations of factor XII and factor XI were in the normal
      range. No differences were detected in the admission values between survivors and
      nonsurvivors, nor between patients with positive or negative blood cultures.
      However, subsequent values demonstrated a difference in values between survivors
      and nonsurvivors. Survivors showed improvement in high molecular weight kininogen
      values and higher than normal factor V values, as compared with nonsurvivors.
      CONCLUSIONS: Low or persistently low serial factor XII, high-molecular-weight
      kininogen and factor V values are associated with a poor prognosis, whereas high
      or increasing values of factor XII, high-molecular-weight kininogen,
      prekallikrein, and factor V all correlate with a favorable outcome.

PMID- 7528120
TI  - [Sharing antigenic determinant of colon carcinoma between serous and mucinous
      tumors of the ovary].
AB  - Expression of colon-ovarian tumor antigen (COTA) in serous and mucinous tumors of
      the ovary was determined immunohistochemically, using monoclonal antibody SC13A
      against colon carcinoma antigen as a probe. In 67 serous tumor of the ovary, the
      frequency of expression was 90.0% in the cystadenocarcinomas, 71.4% in the
      borderline cystadenomas, and only 8.0% in the cystadenomas. In 44 mucinous tumors
      of the ovary, the SC13A marker was expressed in 87.5% of the malignant tumors,
      80.0% of the borderline tumors, and 25.8% of the benign cystadenomas. And in 20
      samples of normal ovarian tissue a negative immunostaining for the SC13A was
      found. These findings showed that the serous and the mucinous tumors share the
      same antigenic determinant of colon cancer, and the percentage expression of
      which is significantly higher in the malignant than in the benign and the
      borderline tumors, as well as in the normal ovarian tissues (P < 0.005). The
      marker might be valuable for further studies of these tumors.

PMID- 7528121
TI  - Automatic detection of clustered, fluorescent-stained nuclei by digital image
      based cytometry.
AB  - Automatic image-based cytometry (IC) can conveniently quantify the distributions
      of several specific, fluorescence-labeled molecules within individual, isolated
      cells of slide- or tissue-based specimens. However, many specimens contain
      clusters of cells or nuclei that are not detected as individual entities by
      existing automatic methods. We have developed analysis algorithms which detected
      individual nuclei occurring in clusters or as isolated nuclei. Specimens were
      labeled with a fluorescent DNA stain, imaged and the images were segmented into
      regions of nuclei and background. Clusters of nuclei, identified by their size
      and shape, were divided into individual nuclei by searching for dividing paths
      between nuclei. The paths, which need not be straight, possessed the highest
      average gradient per pixel. In addition, both high- and low-pass filtered images
      of the original image were analyzed. For each individual nucleus, one of the
      three segmented regions representing the nucleus (from either the original or one
      of two filtered images) was chosen as the final result, based on the closeness of
      the regions to average nuclear morphology. The algorithms correctly detected a
      high proportion of isolated (328/333) and clustered (254/271) nuclei when applied
      to images of 2 microns prostate and breast cancer sections. Thus, these
      algorithms should enable much more accurate detection and analyses of nuclei in
      intact specimens.

PMID- 7528122
TI  - Isolation and characterization of a Chinese hamster ovary cell mutant with
      improved staining for indo-1.
AB  - Chinese hamster ovary (CHO) 10B2 cells do not stain well with indo-1 and thus
      cannot be used for experiments to measure intracellular calcium using this dye.
      We have isolated a mutant CHO cell line (CHO IS1) that stains quite well with
      indo-1 and that has virtually identical growth characteristics and heat
      sensitivity as the parent line. The mutant was isolated by sorting individual
      mutagenized cells with high indo-1 fluorescence and cloning them. Since it has
      been reported that cells with multiple drug resistance (MDR+) can pump out
      various fluorescent dyes, the mutant and parent lines were characterized for
      Hoechst 33342 staining, Adriamycin toxicity, and P-glycoprotein expression, which
      are markers of the MDR phenotype. P-Glycoprotein was measured with the C219
      antibody using flow cytometry. Multidrug-resistant cells (CHRC5) were used as
      positive controls. The IS1 cells stained as well with Hoechst 33342 as fixed 10B2
      cells, and much better than unfixed 10B2 cells. The IS1 cells were 10- to 30-fold
      more sensitive to Adriamycin than the 10B2 cells, and both cell lines were much
      more sensitive than the CHRC5 cells. The amount of P-glycoprotein was similar in
      both 10B2 and IS1 cell lines, but was about fivefold lower than the CHRC5 cells.
      Thus, the poor staining for indo-1 in the 10B2 cells may not be caused by the P
      glycoprotein MDR pump, but by a different efflux pathway. Alternatively, the P
      glycoprotein may be altered and less efficient in the CHO IS1 cells.

PMID- 7528123
TI  - Effect of fixation on quantification of the expression of leucocyte function
      associated surface antigens.
AB  - The surface expression of adhesion molecules and other function-associated
      antigens on peripheral blood leucocytes may be measured by flow cytometry.
      However, quantification of these antigens is difficult, because their expression
      can be rapidly and artefactually modulated if the cells are activated in vitro.
      Consequently, it is common, when analyzing these antigens either: (1) to label
      leucocytes in whole blood at 4 degrees C, to lyse erythrocytes and then fix the
      leucocytes, or (2) to fix the leucocytes in whole blood, to lyse the
      erythrocytes, and then label the leucocytes. We have compared the mean
      fluorescence intensity (MFI) values for CD11b, CD18, and L-selectin (Leu-8 and
      TQ1 epitopes) on human peripheral blood leucocytes, using these two approaches.
      In addition, we have simultaneously evaluated how anticoagulants (acid citrate,
      K3EDTA, and heparin) and the presence or absence of divalent metal ions (Ca2+ and
      Mg2+) affect the expression levels of these antigens. The results for all four
      epitopes varied markedly depending on the preparation procedure used but were
      less affected by the choice of anticoagulant and whether divalent cations were or
      were not present in the media used for cell preparation and labelling. Comparison
      of the results obtained using these procedures, which involve fixation with
      formaldehyde, with those obtained by a recently developed procedure in which
      unfixed leucocytes were labelled with the vital nuclear dye LDS-751 and
      antibodies together, then analysed in unlysed whole blood at 4 degrees C, showed
      that formaldehyde-based preparation techniques underestimated the expression
      (MFI) of CD18, Leu-8, and TQ1. It is recommended that, whenever practicable,
      measurements are made on unfixed cells stained using the newer procedure.

PMID- 7528124
TI  - A flow cytometric method using Hoechst 33342 and propidium iodide for
      simultaneous cell cycle analysis and apoptosis determination in unfixed cells.
AB  - A flow cytometric method to detect apoptotic cells is described. This method is
      based on the detection of differences in chromatin condensation with Hoechst
      33342 as a probe and the detection of dead cells with propidium iodide as a probe
      for membrane damage. By this method it was possible to detect, in the same sample
      and at the same time, intact cells, cells undergoing apoptosis, and dead cells
      resulting from apoptotic and/or necrotic processes. The method was successfully
      applied to the detection of apoptotic cells in two human cell models: cultured
      polymorphonuclear cells and the U937 cell line treated with antitumoral drugs.
      Staining specificity for apoptotic cells was controlled by cell sorting of the
      presumed apoptotic population, followed by morphologic examination or DNA
      analysis of the sorted populations. The usefulness of such a method is discussed
      in terms of applications in the analysis of heterogeneous clinical samples,
      populations with low DNA degradation during apoptosis, and cell cycle position of
      the apoptotic cells.

PMID- 7528125
TI  - New anticoagulant strategies. Current status and future potential.

PMID- 7528126
TI  - Evaluation of antiepileptic drug efficacy. A review of clinical trial design.
AB  - Up to 30% of patients with epilepsy are not adequately treated with currently
      available antiepileptic drugs. Despite a need for new agents, few were developed
      after valproic acid (sodium valproate), which appeared in the 1970s. This picture
      has changed recently. A number of new antiepileptic drugs have been approved for
      marketing, and additional approvals are expected soon. The evidence in the form
      of adequate and well controlled studies supporting the efficacy of each of these
      new drugs has included (and in some cases been wholly composed of) placebo
      controlled add-on trials, showing the viability of that design. Add-on trials,
      which compare a new drug with placebo in the presence of a stable regimen of
      antiepileptic drug therapy, can be conducted as parallel or cross-over designs.
      These designs have been considered insensitive because they are conducted in
      patients refractory to available antiepileptic drugs, but add-on trials have
      proved able to identify effective new drugs. They also permit long term
      evaluation and provide information, including drug interaction data, in one of
      the major clinical contexts where a new antiepileptic drug may be used. New
      designs now allow the evaluation of antiepileptic effectiveness in other clinical
      contexts, including monotherapy, and provide alternatives when drug interactions
      obscure add-on trial interpretation. The key feature of this class of monotherapy
      designs is basing patients' trial duration on their seizure activity rather than
      on a fixed time period. This is accomplished by defining 'therapeutic failure'
      criteria which serve to assess efficacy of the test agent while protecting
      patient safety.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528129
TI  - Choosing the right beta-blocker. A guide to selection.
AB  - beta-Blockers have been in clinical use for 30 years, and have an accepted role
      in (among others) the treatment of high blood pressure, the secondary prevention
      of myocardial infarction and the treatment of arrhythmias. Their place in the
      treatment of heart failure is currently under investigation. The drugs available
      in the 1970s and early 1980s were subjected to intense investigation. A new
      generation of beta-blockers, including some such as carvedilol and bucindolol,
      with vasodilating properties, is now appearing. As yet these later agents have
      not been the subject of large clinical trials. Clinical practice involves the
      treatment of individual patients with defined dosages of particular drugs. It is,
      therefore, not acceptable to base practice on theories derived from the clinical
      pharmacology of a particular drug, on the results of small trials or on a meta
      analysis of results from a number of trials that were individually inadequate.
      Clinical practice must follow the results of large-scale trials in defined
      populations. The major trials in hypertension, myocardial infarction, arrhythmias
      and heart failure provide the best evidence for the use of individual beta
      blockers in each of these clinical situations. In patients with high blood
      pressure, beta-blockers do not seem to have any particular advantage over other
      hypotensive agents. In myocardial infarction, relatively late use of a beta
      blocker undoubtedly reduces fatality, though the value of early treatment is less
      clear. beta-Blockers are not powerful antiarrhythmics, but they do appear to
      prevent sudden death. Their possible role in heart failure is perhaps the most
      interesting current field of beta-blocker research. There are very few
      comparative studies of beta-blockers, and it is difficult to make precise
      recommendations. None of the new generation of beta-blockers has yet been used in
      a trial that is large enough trial for any of them to be accepted for routine use
      in preference to older drugs. The use of individual beta-blockers, as with any
      drug, should follow the results of clinical trials. Propranolol and atenolol have
      been studied most intensely in hypertension. For secondary prevention of
      myocardial infarction, the evidence is best for timolol. Sotalol is probably the
      best antiarrhythmic among the beta-blockers. Whether any individual beta-blocker
      is best for heart failure remains to be seen.

PMID- 7528131
TI  - Abciximab (c7E3 Fab). A review of its pharmacology and therapeutic potential in
      ischaemic heart disease.
AB  - Abciximab (c7E3 Fab) is a chimaeric human-murine monoclonal antibody Fab
      (fragment antigen binding) fragment. It binds to the platelet glycoprotein
      IIb/IIIa receptor and inhibits platelet aggregation. In two double-blind placebo
      controlled trials, abciximab therapy reduced the incidence of ischaemic
      complications during the initial postoperative period (30 days or until hospital
      discharge) in high-risk patients undergoing percutaneous coronary angioplasty or
      directional atherectomy. It also reduced the incidence of clinical restenosis
      compared with placebo during longer term (6 months) follow-up of these patients.
      Although abciximab delayed the need for coronary artery bypass graft surgery, it
      did not reduce the proportion of patients ultimately requiring this procedure.
      The drug was generally well tolerated in clinical trials, with bleeding
      complications being the major adverse event. Abciximab is at an early stage of
      its clinical introduction and, not surprisingly, some aspects of its use remain
      to be further assessed. Nevertheless, results show the addition of abciximab to
      standard aspirin plus heparin therapy during coronary angioplasty or directional
      atherectomy improves the outcome of the revascularisation procedure in patients
      with a high risk of subsequent acute ischaemic complications. The results of
      further trials defining the optimum dosage of heparin when administered with
      abciximab, and evaluating the role of abciximab in a wider range of patients, are
      eagerly awaited.

PMID- 7528127
TI  - Current status of photodynamic therapy in oncology.
AB  - Photodynamic therapy (PDT) is a cancer treatment based on the accumulation in
      malignant tissue of a photosensitiser with low systemic toxicity. Subsequent
      illumination induces a type II photochemical reaction with singlet oxygen
      production that results in destruction of biomolecules and subcellular
      organelles. The first full clinical report of PDT dates from 1976.
      Haematoporphyrin derivative, a complex mixture of porphyrins, was initially used
      as a photosensitiser. An enriched fraction (porfimer sodium) is now the most
      commonly used clinical agent. After systemic administration porphyrins bind to
      albumin and lipoproteins. Accumulation occurs mainly in tumours and organs of the
      reticuloendothelial system. The light of an argon-dye laser can be tuned to the
      appropriate wavelength and delivered either superficially, interstitially or
      intraluminally. Light distribution can be assessed by using a radiation transport
      model and tissue optical properties, or direct measurement with light detectors.
      The effects of PDT depend in a complex way on: characteristics, tissue
      concentration and localisation of the photosensitiser; the target tissue optical
      properties and oxygenation; activation wavelength, power density and treatment
      regimen. Future research is directed towards: better photosensitisers (i.e.
      phthalocyanines, chlorins or protoporphyrin IX endogenously produced from 5
      aminolevulinic acid); improved light generation and delivery; and combination
      with hyperthermia, chemotherapy, radiotherapy or surgery. Adjuvant intraoperative
      PDT is a promising approach to destroying residual tumour after surgery.

PMID- 7528130
TI  - Treatment of Kaposi's sarcoma. Current guidelines and future perspectives.
AB  - Kaposi's sarcoma is the most common malignancy associated with HIV infection, and
      the morbidity and mortality attributable to AIDS-related Kaposi's sarcoma (AIDS
      KS) may be increasing. No curative therapy is available for AIDS-KS, but
      palliative therapy can eliminate or reduce cosmetically unacceptable lesions,
      reduce painful or unsightly oedema or lymphadenopathy, shrink symptomatic oral
      lesions and relieve symptoms caused by visceral involvement. Strategies currently
      employed to treat the various clinical problems encountered in AIDS-KS include
      single- and multi-agent cytotoxic chemotherapy, treatment with interferon-alpha,
      radiotherapy, and other local therapies. Current clinical research is focusing on
      use of liposome-encapsulated cytotoxic agents and treatment with substances that
      inhibit angiogenesis. Any treatment plan for AIDS-KS must be flexible and must be
      based on the patient's overall clinical and immunological status as well as
      therapeutic goals. Limited local disease is usually amenable to treatment with
      local measures. Extensive, symptomatic AIDS-KS warrants systemic treatment. The
      response of mucocutaneous lesions to low dose systemic cytotoxic chemotherapy is
      typically excellent. Treatment with interferon-alpha may also be beneficial in
      this setting. Multi-agent chemotherapeutic regimens are usually reserved for
      treatment of patients most severely affected by AIDS-KS. It is hoped that
      liposome-encapsulated cytotoxic chemotherapy and antiangiogenic therapies will
      prove more effective and less toxic than the treatment strategies currently in
      use.

PMID- 7528132
TI  - Dirithromycin. A review of its antimicrobial activity, pharmacokinetic properties
      and therapeutic efficacy.
AB  - Dirithromycin is a new macrolide with a spectrum and degree of in vitro
      antimicrobial activity similar to that of erythromycin. Compared with
      erythromycin, dirithromycin has a long elimination half-life enabling once-daily
      administration, and it also achieves a greater cellular:extracellular
      concentration ratio and higher concentration in some tissues. Multicentre double
      blind clinical trials have shown dirithromycin to be similar in efficacy to
      erythromycin in the treatment of uncomplicated bacterial infections of the
      respiratory tract and of skin and soft tissues. Since dirithromycin is at least
      as well tolerated as erythromycin, with its convenient administration schedule
      and pharmacokinetic profile it is a useful alternative to erythromycin in the
      treatment of appropriate community-acquired infections. Definition of the place
      of dirithromycin relative to that of the other newer macrolides awaits the
      results of further suitably designed therapeutic trials.

PMID- 7528133
TI  - Loratadine. A reappraisal of its pharmacological properties and therapeutic use
      in allergic disorders.
AB  - Loratadine is a long-acting antihistamine agent, exhibiting partial selectivity
      for peripheral histamine H1-receptors. To date, loratadine has been evaluated in
      allergic rhinitis, urticaria and, to a limited extent, in asthma. In several
      large controlled comparative clinical studies, loratadine was superior to
      placebo, faster acting than astemizole and as effective as azatadine, cetirizine,
      chlorpheniramine (chlorphenamine), clemastine, hydroxyzine, mequitazine and
      terfenadine in patients with allergic rhinitis and chronic urticaria. The
      clinical effectiveness of loratadine in asthma is at present unclear. Loratadine
      is well tolerated. At dosages of 10 mg daily, commonly reported adverse events
      were somnolence, fatigue and headache. Sedation occurred less frequently with
      loratadine than with azatadine, cetirizine, chlorpheniramine, clemastine and
      mequitazine. Serious ventricular arrhythmias, as reported with some other second
      generation histamine H1-receptor antagonists, have not been observed with
      loratadine to date. Thus, loratadine, with its attributes of once daily
      administration, fast onset of action and essentially nonsedating properties,
      would appear to be an appropriate first-line agent for the treatment of allergic
      rhinitis or urticaria.

PMID- 7528134
TI  - Tinzaparin. A review of its pharmacology and clinical potential in the prevention
      and treatment of thromboembolic disorders.
AB  - Tinzaparin, a low molecular weight (LMW) heparin with an average molecular weight
      of 4.5 +/- 1.5 kD, has greater bioavailability and a longer duration of action
      than unfractionated heparin, allowing it to be administered once daily by
      subcutaneous injection for both prophylaxis and treatment of deep venous
      thrombosis (DVT). Like other members of its class, tinzaparin has a greater ratio
      of antifactor Xa/anti-factor IIa activity than unfractionated heparin, providing
      the theoretical advantage of similar antithrombotic efficacy with a diminished
      risk of haemorrhagic complications. In a small number of clinical trials,
      tinzaparin was found to be more effective than intravenous dextran or oral
      warfarin sodium as prophylaxis against DVT in high-risk patients undergoing
      orthopaedic surgery, and more effective than subcutaneous heparin in both general
      surgical patients and medical patients with an immobilising illness. When used
      for the treatment of established DVT, tinzaparin was more effective in preventing
      DVT recurrence than intravenous heparin, both initially and during a 3-month
      follow-up period when patients received warfarin sodium. Tinzaparin was also used
      successfully in one small study to maintain the patency of haemodialysis circuits
      over a 6-month period, with favourable effects on the lipid profile of such
      patients. Tinzaparin is well tolerated, the most frequent complication being
      injection site haematoma. In comparative trials, tinzaparin was associated with
      fewer major haemorrhagic complications than intravenous heparin (when used for
      treatment of venous thrombosis), but more than warfarin sodium. Other adverse
      events which have been reported in tinzaparin-treated patients include elevated
      liver enzyme levels and thrombocytopenia. Thus, although clinical experience is
      limited at present, available data suggest that, in common with other LMW
      heparins, tinzaparin is likely to prove an effective alternative to
      unfractionated heparin for both the prevention and treatment of DVT, with the
      advantage of more convenient administration and decreased monitoring
      requirements.

PMID- 7528137
TI  - Role of L-type calcium channel modulation in nonconvulsive epilepsy in rats.
AB  - Old male Wistar rats spontaneously showing hundreds of spike-wave discharges
      daily were used to investigate the role of calcium ions in nonconvulsive
      epilepsy. The effects of the L-type calcium channel blocker nimodipine and the L
      type channel opener BAY K 8644 on number and duration of these spike-wave
      discharges were investigated. In rats aged 84-94 weeks standard EEG electrodes
      were chronically implanted; animals were allowed to recover for 10 days. After a
      baseline registration, nimodipine 2.2, 8.8, and 35.2 mg/kg or BAY K 8644 in
      dosages of 0.12, 0.47, and 1.88 mg/kg was administered. A control group received
      the solvent. EEG recordings were made to evaluate drug effects. The highest dose
      of nimodipine increased the number of spike-wave discharges, whereas BAY K 8644
      reduced the number of spike-wave discharges dose dependently. The highest dose of
      BAY K 8644 also induced fatal convulsions in 3 animals. Our results demonstrate
      that the L-type calcium antagonist nimodipine facilitates spike-wave discharges
      and that the L-type calcium agonist BAY K 8644 protects against these discharges,
      in contrast to previous results suggesting that calcium channel blockers act as
      antiepileptic drugs (AEDs) and that calcium channel openers act as convulsants.
      Our results are a further example of the different pharmacologic profile of
      convulsive and nonconvulsive epilepsy and are also in contrast to what has been
      described for T-type calcium channel modulation. We therefore propose that
      modulation of L-type and T-type calcium channels have opposite effects in
      nonconvulsive epilepsy.

PMID- 7528136
TI  - A novel approach to the management of oesophageal tube overgrowth by tumour.

PMID- 7528138
TI  - Distinct signaling pathways mediate phorbol-ester-induced and cytokine-induced
      inhibition of erythropoietin gene expression.
AB  - Hypoxia-induced erythropoietin (Epo) production in vitro is suppressed by
      interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF) and phorbol
      esters. Herein, the Epo-synthesizing human hepatoma cell line HepG2 was used to
      investigate whether protein kinase C (PKC) is involved in the inhibitory action
      of the cytokines. Within 1 h after the onset of hypoxia, Epo mRNA levels were
      markedly increased in untreated HepG2 cells as quantitated by competitive reverse
      transcription PCR. The cytokines IL-1 beta and TNF prevented this hypoxia-induced
      increase in Epo mRNA levels. In phorbol-ester-treated cells first inhibitory
      effects on Epo mRNA levels were observed only after 3 h. Western blot analyses
      revealed the presence of four isoenzymes of PKC in HepG2 cells. None of these
      isoenzymes was translocated in response to TNF or IL-1 beta, suggesting that the
      cytokines do not activate PKC in HepG2 cells. In contrast, phorbol esters
      translocated and, upon prolonged exposure, down-regulated PKC isoenzymes alpha
      and epsilon. Activation of protein kinase A by dibutyryl-cAMP partially
      antagonized the cytokine-dependent inhibition of Epo production but did not
      influence the inhibitory effect of phorbol esters. Endogenous cAMP levels in
      HepG2 cells were unchanged by cytokine treatment. Obviously, at least two
      signaling pathways exist that can confer inhibition of Epo production in HepG2
      cells. One of these may be mediated by down-regulation of the PKC alpha or
      epsilon isoenzyme. The other pathway, however, which is triggered by IL-1 beta
      and TNF, is independent of PKC.

PMID- 7528135
TI  - Malignant bile-duct obstruction: experience with self-expanding metal
      endoprostheses (Wallstents) in Austria.
AB  - Fifty-two patients in nine Austrian hospitals were treated with biliary self
      expanding metal endoprostheses (Wallstents) for malignant biliary obstruction,
      and followed up retrospectively using questionnaires, answered by the
      endoscopists. Stent placement was successful in all patients. The technical
      failure rate at the first attempt was 7.7%, and stenting-associated mortality was
      3.8% due to mispositioning of stents, leading in two cases to death. The 30-day
      mortality was 13.5%, and early complications occurred in 15.4%. The median
      survival was 216 days, and the median stent patency was 291 days. During follow
      up, stent occlusion was observed in ten patients, acute cholangitis in 12
      patients, acute pancreatitis in three patients, acute cholecystitis in one
      patient, and duodenal ulceration due to stent erosion in one patient. Routine use
      of biliary self-expanding metal endoprostheses by averagely experienced
      endoscopists can be recommended. Attention has to be paid to the correct
      placement of the guidewire and stent.

PMID- 7528139
TI  - The widespread expression of angiogenin in different human cells suggests a
      biological function not only related to angiogenesis.
AB  - Angiogenin is a secreted polypeptide that induces neovascularization in vivo. The
      expression of angiogenin by human cells in culture was investigated by using a
      specific radioimmunoassay and by cDNA hybridization. Angiogenin immunoreactivity
      was widely but differentially produced by anchorage-dependent growing cells
      including vascular endothelial cells from saphenous and umbilical veins, aortic
      smooth muscle cells, fibroblasts (from embryos, new-borns and adults), and tumour
      cells. Endothelial cells from saphenous veins and the endothelium-derived
      EA.hy926 cell line released immunoreactivity whatever the stage of the culture,
      including release at the lag phase, during exponential growth and at the
      confluent phase. However, the rate of accumulation of angiogenin varied as a
      function of EA.hy926 cell density. As compared to anchored cells, normal
      peripheral blood cells and tumour cells of myelomonocytic and megakaryocytic
      origin did not noticeably secrete angiogenin except at low levels. A myeloma cell
      line supernatant contained as much angiogenin cross-reactivity as did anchored
      cells, while four tumour T-cell lines expressed the cross-reactivity at different
      levels, i.e. from undetectable levels to a high level. A 0.9-kb angiogenin
      messenger RNA was detected by Northern-blot analyses in a variety of
      representative cells correlating with the presence of immunoreactivity in the
      cell-culture media. The widespread expression pattern of angiogenin suggests a
      physiological function that is not restricted to the neovascularization process.

PMID- 7528140
TI  - Expression and characterisation of a very-late antigen-4 (alpha 4 beta 1)
      integrin-binding fragment of vascular cell-adhesion molecule-1.
AB  - We have used an Escherichia coli expression system to produce forms of vascular
      cell-adhesion molecule-1 (VCAM-1) containing the first two and three supposed
      immunoglobulin-like domains. A form consisting of the first two domains of VCAM-1
      is shown to promote very-late antigen-4-dependent spreading of a melanoma cell
      line comparable to that found for the equivalent region in the full seven-domain
      form. Preliminary structural analysis by CD and NMR is consistent with an
      immunoglobulin fold which is predicted from sequence comparison studies.

PMID- 7528143
TI  - Role of surgery in the therapy of epilepsy.
AB  - A brief overview is given on the concepts and methods of presurgical evaluation,
      as well as on the principles and techniques of surgical treatment of epilepsies.
      Lesion-oriented surgery is differentiated from epilepsy-oriented lesional surgery
      and from surgery for epilepsy sensu stricto. The rationale for 'curative' and
      'palliative' interventions is discussed. Selective amygdalohippocampectomy,
      anterior temporal lobe resection, extratemporal topectomies, subtotal functional
      hemispherectomies, stereotactic interventions, anterior corpus callosum section
      and multiple subpial transection are briefly described. Results of a survey done
      on the occasion of the 2nd International Palm Desert Conference on the 'Surgical
      Treatment of the Epilepsies' are summarized.

PMID- 7528142
TI  - Selective activation and inhibition of calmodulin-dependent enzymes by a
      calmodulin-like protein found in human epithelial cells.
AB  - A calmodulin-like protein, which is identical in size and 85% identical to
      vertebrate calmodulin, was recently identified by 'subtractive hybridization'
      comparison of transcripts expressed in normal versus transformed human mammary
      epithelial cells. Unlike the ubiquitous distribution of calmodulin, calmodulin
      like protein expression is restricted to certain epithelial cells, and appears to
      be modulated during differentiation. In addition, calmodulin-like protein levels
      are often significantly reduced in malignant tumor cells as compared to
      corresponding normal epithelial cells. The current studies compare calmodulin
      like protein functions with those of calmodulin. We find that calmodulin-like
      protein activation of multifunctional Ca2+/calmodulin-dependent protein kinase II
      (calmodulin kinase II) is equivalent to activation by calmodulin, but that four
      other calmodulin-dependent enzymes, cGMP phosphodiesterase, calcineurin, nitric
      oxide synthase, and myosin-light-chain kinase, display much weaker activation by
      calmodulin-like protein than by calmodulin. In the case of myosin-light-chain
      kinase, calmodulin-like protein competitively inhibits calmodulin activation of
      the enzyme with a Ki value of 170 nM. Thus, calmodulin-like protein may have
      evolved to function as a specific agonist of certain calmodulin-dependent
      enzymes, and/or as a specific competitive antagonist of other calmodulin
      dependent enzymes.

PMID- 7528141
TI  - Structural determinants of substrate selection by the human insulin-receptor
      protein-tyrosine kinase.
AB  - Using NMR spectroscopy to visualise tyrosine phosphorylation kinetics in real
      time, we have investigated the sequence-dependent determinants of the selectivity
      of the human insulin receptor protein-tyrosine kinase for different tyrosine
      residues. The peptides used encompass the multiple-tyrosine-containing
      autophosphorylation site sequences from the insulin receptor kinase core domain
      (Tyr1158, Tyr1162 and Tyr1163) and from its specific C-terminal tail domain
      (Tyr1328 and Tyr1334). Comparison of the phosphorylation kinetics with those
      found for the tyrosine residues on a peptide comprising the regulatory tyrosine
      phosphorylation site of cdc2 points to the role of the primary sequence context
      of the phosphate acceptor. The particularly deleterious influence of a basic
      residue immediately C-terminal to the tyrosine is discussed in relation to the
      autophosphorylation properties of the regulatory loop regions of the insulin and
      epidermal growth factor receptor kinases. The data further suggest that receptor
      tyrosine kinase active sites and their substrate targets act in concert to ensure
      that specific downstream effects are activated.

PMID- 7528144
TI  - Tachykinins and kinins in antigen-evoked plasma extravasation in guinea-pig nasal
      mucosa.
AB  - The plasma extravasation evoked by instillation of 5% ovalbumin in the nasal
      mucosa of sensitized guinea-pigs was potentiated by the neutral endopeptidase
      inhibitor, phosphoramidon, and was reduced by the tachykinin NK1 receptor
      antagonist, CP-96,345. The bradykinin B2 receptor antagonist, HOE 140, also
      reduced the plasma extravasation evoked by the antigen. The combination of HOE
      140 and CP-96,345 did not increase further the inhibition caused by HOE 140
      alone. Plasma extravasation evoked by instillation of capsaicin was abolished by
      CP-96,345. HOE 140 blocked and CP-96,345 markedly reduced plasma extravasation
      caused by instillation of bradykinin. Plasma extravasation evoked by instillation
      of substance P was not affected by HOE 140. We conclude that antigen challenge
      causes plasma extravasation in the nasal mucosa of sensitized guinea-pigs, an
      effect that is due in part to the release of tachykinins from sensory nerve
      endings. Our evidence suggests that tachykinin release in response to antigen is
      provoked mainly by the release of kinins.

PMID- 7528128
TI  - Recognition and treatment of shingles.
AB  - Varicella zoster virus (VZV) is responsible for a primary infection (varicella)
      followed by a latency, eventually resulting in herpes zoster (shingles). The
      replication cycle of VZV is normally interrupted after varicella. Consequently,
      VZV remains dormant in the organism. Reactivation occurs after viraemia, and the
      development of tissue alterations (skin and viscera) depends on the immunological
      status of the patient. Diagnosis of herpes zoster relies on clinical recognition
      and cytological and histological evaluations combined with immunohistochemistry
      and molecular biology techniques. Treatment of herpes zoster primarily relies
      upon antiviral drugs and incidentally on immunomodulating agents, specific
      immunoglobulins, antimicrobial agents, antiviral enzymes and corticosteroids.
      Drugs with a clinically relevant activity against varicella zoster virus
      infections include aciclovir, adenosine monophosphate, bromodeoxyuridine,
      desciclovir, fiacitabine, idoxuridine, interferon-alpha and vidarabine. Among
      them, aciclovir appears to be a first-line agent. Its efficacy has been well
      established by many clinical studies. Promising drugs for the future include
      famciclovir, penciclovir, valaciclovir and other molecules currently under
      investigation. Recent and promising improvements in antiviral drug development
      may increase patient compliance, cost-benefit ratios and therapeutic efficacy.

PMID- 7528146
TI  - New modified substrates for discriminating between human DNA polymerases alpha
      and epsilon.
AB  - Two 2'-deoxynucleoside 5'-alpha-methylenephosphonyl-beta, gamma-diphosphates were
      synthesized. They were incorporated into the DNA chain by DNA polymerase alpha
      from human placenta. Meanwhile, they were not recognized by DNA polymerase
      epsilon and beta of the same origin as well as by reverse transcriptases from
      human immunodeficiency virus and avian myeloblastosis virus.

PMID- 7528145
TI  - Comparison of antagonistic effects of sendide and CP-96,345 on a spinally
      mediated behavioural response in mice.
AB  - Intrathecal administration of the tachykinin NK1 receptor agonists, substance P,
      physalaemin, septide and [Sar9, Met(O2)11]substance P, elicited a characteristic
      behavioural response consisting of scratching, biting and licking in mice. The
      behavioural response induced by substance P was significantly inhibited by
      simultaneous intrathecal injection of a tachykinin NK1 receptor antagonist,
      [Tyr6,D-Phe7,D-His9]substance P-(6-11) (sendide), and a non-peptide antagonist,
      [(2S,3S)-cis-2-(di-phenylmethyl)-N-[(2- methoxyphenyl)-methyl]-1
      azabicyclo[2.2.2]octan-3-amine](CP-96,345). The duration of the antagonistic
      effect of sendide was similar to that of CP-96,345. The antagonistic effect of
      sendide on the response induced by tachykinin NK1 receptor agonists was
      approximately 1000 times more potent than that of CP-96,345. Neither antagonist
      inhibited neurokinin A-, D-septide-, neurokinin B- and eledoisin-induced
      scratching, biting and licking responses. Sendide was without effect on motor
      performance as measured by the rotarod test, while motor incoordination was
      elicited only 2 min after intrathecal injection of CP-96,345. These results
      indicate that sendide and CP-96,345 are selective antagonists of tachykinin NK1
      receptors with a long duration of action.

PMID- 7528147
TI  - [The effect of antiandrogen TZP-4238 on corticosteroid hormone in the dog].
AB  - We studied the adrenosuppressive effect of antiandrogen TZP-4238 and its
      metabolites. The binding affinity for the corticosteroid receptor using rat
      hepatic cytosol was in the order 11-OH TZP-4238 > 11, 15-(OH)2 TZP-4238 >> TZP
      4238 > or = 15-OH TZP-4238 > 11-keto TZP-4238. Male beagle dogs aged 1-6 years
      were randomly divided into TZP-4238 (0.05, 0.5mg/kg) treatment groups and CMA
      (0.5mg/kg) treatment group. Each group was administered the drug per os every day
      for 8 weeks. Plasma cortisol, TZP-4238 and its metabolite levels were measured by
      on-line coupling of liquid chromatography with thermospray or atmospheric
      pressure ionization mass spectrometry using selective ion monitoring (LC-MS/SIM).
      LC-MS/SIM provided a sensitive and reliable method of unequivocal confirmation of
      the presence of steroidal drugs in the plasma. The plasma cortisol level was
      lowered below 1 ng/ml at 1 week after oral administration of TZP-4238 at 0.5mg/kg
      or CMA at 0.5mg/kg. The decline continued throughout the treatment for 8 weeks.
      Upon termination of administration, the cortisol level returned to the normal
      level (6ng/ml) by 4 weeks. However in the group given 0.05mg/kg TZP-4238, the
      cortisol level remained within the normal range. To analyze the cortisol
      decreasing mechanism, we administered TZP-4238 at 0.5mg/kg for 7 days to one
      beagle dog. When the plasma 11-OH TZP-4238 level was increased, the cortisol
      level decreased time dependently and the concentration of plasma 11-OH TZP-4238
      which induced 50% inhibition was 2ng/ml. The decrease in the plasma cortisol
      level was highly correlated to the extent of the increase of the plasma 11-OH TZP
      4238 (r2 = 0.840). We conclude that the adrenosuppressive effect of antiandrogen
      TZP-4238 is not due to TZP-4238 itself but its metabolite 11-OH TZP-4238.

PMID- 7528148
TI  - [Effects of antiandrogen TZP-4238 on the prostatic androgen receptor and
      prostatic androgen in rat].
AB  - TZP-4238, a new steroidal antiandrogen, is an orally active drug in rats and
      dogs. The effects of TZP-4238 on the androgen receptor and androgen content were
      examined in comparison with other antiandrogens in rats. The prostate DHT levels
      decreased markedly within 4-8 hr after a single oral administration of TZP-4238
      8mg/kg. The prostatic testosterone concentrations fell below the detection limit
      (5pg/g of tissue) at 4-12 hr after the initiation of treatment. The plasma
      testosterone level also fell to 60% of the control level after 4-8 hr and then
      returned to the normal range. Eight percent of DHT present in normal prostatic
      tissue was located in the nuclear fraction. TZP-4238 reduced the concentration of
      DHT in nuclei to 50% of the normal level. The concentration of the plasma drug
      which induced a 50% decrease in the prostatic DHT, the IC50, was about 10ng/ml,
      while the IC50 value for plasma testosterone was 30-50ng/ml. After oral
      administration of 15-OH TZP-4238, the main metabolite, the level of plasma
      testosterone was significantly elevated above the control level. The androgen
      receptor level was markedly reduced at 24 hr following castration and returned to
      the normal range within 5 hr of a single injection of testosterone. TZP-4238
      reduced the nuclear androgen receptor level to 60% at 24 hr after a single oral
      dose and then, the receptor content returned to its original level. Both 15-OH
      TZP-4238 and cyproterone acetate also reduced the androgen receptor and DHT
      contents to 50%. A series of in vivo studies demonstrated that TZP-4238 inhibited
      the uptake of testosterone and the decrease of DHT and testosterone, and
      decreased the nuclear androgen receptor in the rat prostate.

PMID- 7528149
TI  - [Expression of nitric oxide synthase in enkephalin and dynorphin systems of the
      rat hypothalamus].
AB  - Nitric oxide (NO), a simple gas with free radical chemical properties, is
      synthesized by nitric oxide synthase (NOS) from arginine in neurons and acts as a
      neurotransmitter in the central and peripheral nervous systems. The
      immunohistochemical demonstration of NOS-immunoreactivity and its histochemical
      marker, NADPH-diaphorase activity in many neurons of the hypothalamus, suggest
      that NO plays a role in controlling the production and/or release of hypothalamic
      neuroendocrine peptides. In the present study, the expression of NOS in the
      enkephalin and dynorphin systems of the rat hypothalamus was examined by the
      combined method of the NADPH-diaphorase histochemistry and the
      immunocytochemistry of methionine enkephalin (M-Enk) or dynorphin B (Dyn-B).
      About 6 to 9% of M-Enk immunoreactive neurons in the paraventricular, arcuate and
      ventromedial nuclei expressed NADPH-diaphorase activity. Dyn-B immunoreactive
      neurons, however, showed NADPH-diaphorase activity in high ratio (37%-84%) in the
      supraoptic nucleus and the parvocellular and magnocellular paraventricular
      nucleus. These results revealed that a part of the enkephalin and dynorphin
      neurons in the rat hypothalamus have the ability to produce NO. The high ratio of
      expression of NO in magnocellular neurosecretory dynorphin containing neurons
      suggested that NO participates in controlling posterior pituitary hormone
      secretion together with dynorphin.

PMID- 7528150
TI  - Identification of a target cell antigen recognized by nonspecific cytotoxic cells
      using an anti-idiotype monoclonal antibody.
AB  - Nonspecific cytotoxic cells (NCC) are the teleost equivalent of mammalian natural
      killer (NK) cells. In the present study an anti-idiotypic monoclonal antibody
      (mAb 7D12) was generated against idiotopes on an mAb (mAb 6D3.2) that recognizes
      a putative receptor on NCC. The idiotypic specificity of mAb 7D12 was determined
      in competition assays by incubating biotinylated mAb 7D12 with mAb 6D3.2
      hybridoma cells following preincubation with combinations of biotinylated 7D12
      with either nonbiotinylated homologous or heterologous mAb. The ligand recognized
      by mAb 7D12 (determined by flow cytometry) was found on cells from the anterior
      kidney, spleen, thymus, PBL, liver, and brain. NCC lysis of IM-9 targets was
      inhibited 76% following preincubation of the target cells with different
      concentrations of mAb 7D12. The involvement of the ligand recognized by mAb 7D12
      in the NCC lytic cycle was determined by showing that this mAb produced 50%
      inhibition of NCC conjugate formation with NC-37 target cells. Biochemical
      analysis using SDS-PAGE and Western blotting revealed that mAb 7D12 recognized 54
      and 65 M(r) proteins in IM-9 target cell lysates. These studies demonstrated that
      an idiotope on a NCC specific anti-receptor mAb was an "internal image" of a
      target cell ligand. The anti-id mAb generated against this image (idiotope)
      inhibited NCC cytotoxicity and thus was equivalent to an NCC receptor that binds
      to a target cell ligand involved in NCC recognition.

PMID- 7528152
TI  - Phylogenetic analysis of the genus Microbacterium based on 16S rRNA gene
      sequences.
AB  - 16S rRNA gene (rDNA) studies of the six species of the genus Microbacterium, M.
      lacticum, M. laevaniformans, M. dextranolyticum, M. imperiale, M. arborescens and
      M. aurum, were performed and the primary structures were compared with those of
      29 representative actinobacteria and related organisms. Phylogenetic analysis
      indicated that six species of the genus Microbacterium and representative four
      species of the genus Aureobacterium appear to be phylogenetically coherent as was
      suggested by Rainey et al., although the peptidoglycan types of these two genera
      are different (peptidoglycan type B1 or B2). Thus, the phylogenetical analyses
      revealed that members of actinobacteria with group B-peptidoglycan do not cluster
      according to their peptidoglycan types, but form compact cluster different from
      actinobacteria or actinomycetes with group A-peptidoglycan.

PMID- 7528153
TI  - Discrimination of Mycobacterium avium-Mycobacterium intracellulare strains by
      genomic DNA fingerprinting with a 16S rRNA gene probe.
AB  - Ribotyping was investigated as a means of distinguishing ten different serotyped
      reference strains and seven epidemiologically unrelated isolates of Mycobacterium
      avium-Mycobacterium intracellulare using a labelled 16S rDNA probe. Thirteen
      restriction enzymes were screened towards an accurate discrimination of strains.
      Two selected restriction enzymes (SacI and ClaI) enabled us to classify the 17
      strains into ten ribotypes with an index of discrimination of 0.897. Typeability
      and reproducibility of the method reached 100%. The patterns obtained exhibited
      polymorphism of RE fragments within and outside the 16S rRNA gene and may be
      useful for epidemiological studies.

PMID- 7528151
TI  - [Outlook for the future in the treatment of diabetic retinopathy].
AB  - With regard to diabetic retinopathy, in addition to the demonstration by the DCCT
      study that prevention is achieved by good metabolic control, our present
      knowledge on physiopathology leads us to imagine three types of possible
      therapeutic approach; inhibition of glucotoxicity, improvement of capillary flow,
      blockade of angiogenesis. 1) Inhibition of glucotoxicity Aldose reductase
      inhibitors can prevent cataract in diabetic or galactosemic rats. The effect of
      these drugs on retinopathy, evaluated in some clinical trials, remains
      controversial, suggesting a minor role. Aminoguanidine is an inhibitor of
      formation of advanced glycosylation end-products (AGE). This compound has been
      tested on a model of experimental retinopathy in rats. Parallel to the AGE
      decrease in retina, formation of microaneurysms and loss of endothelial cells in
      capillaries were delayed. Clinical tolerance allows human application and
      randomised trials will give further information on this potentially efficient
      drug. 2) Improvement of capillary flow This objective can be obtained by drugs
      inhibiting platelet aggregation or improving erythrocyte or leucocyte
      deformability. Clinical trials using such compounds were not very conclusive. 3)
      Blockade of angiogenesis Proliferation of new vessels is a rather severe stage of
      diabetic retinopathy. Angiogenesis is due to factors locally produced (as FGF,
      TGF and u-PA produced by anoxic tissues), systemic (IGF-1) or released by
      inflammatory reaction (IL1, TNF alpha and beta). One imagines usage of drugs
      which inhibit these factors and prevent angiogenesis. At the present time, two
      approaches have been used in proliferative retinopathy worsening despite
      panphotocoagulation; analogues of somatostatin and interferon alpha. The
      promissing results of these pilot studies have to be confirmed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7528155
TI  - Digestion of human chromosomes by means of the isoschizomers MspI and HpaII.
AB  - The isoschizomers MspI and HpaII are four base cutter (C decrease CGG)
      restriction endonucleases, HpaII being sensitive to methylation of the internal
      cytosine. Human chromosomes treated with MspI have produced inconsistent results
      between laboratories, while HpaII has always been described as a nonbanding
      enzyme when used on human chromosomes. These results have been explained on the
      basis of both rarity of the CpG doublet in vertebrate genomes and high rate of
      CpG methylation (5mCpG). We demonstrated consistent banding patterns subsequent
      to digestions with MspI and HpaII. On euchromatin, MspI (but not HpaII) digests
      the DNA of R regions and thus R-bands apparently contain many more CCGG sites
      (mostly methylated) than G-bands. In heterochromatin, extensive digestion of the
      9q12 region not only by MspI but also by HpaII reveals a heterochromatic domain
      with a high frequency of unmethylated CCGG sites, most probably within the
      satellite 3 DNA fraction. In addition, enzymatic digestions of the Yq12
      heterochromatin, when this region is undercondensed by 5-azacytidine, contribute
      to deepen the insight into the mechanism of action of this cytidine analog and at
      the same time reinforce the idea of the heterogeneity of this chromosome region
      where domains with unmethylated CCGG sites may also exist.

PMID- 7528154
TI  - Presence of different O antigen forms in three isolates of one clone of
      Escherichia coli.
AB  - Escherichia coli strains ECOR2, ECOR3 and K-12 are very closely related in
      genotype as indicated by multilocus enzyme electrophoresis. We show that they
      have very different rfb regions indicating that recombination has occurred in
      this region, and we suggest that it may be associated with niche adaptation.

PMID- 7528156
TI  - Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice.
AB  - We report that keratin 8 (mK8) gene disruption causes colorectal hyperplasia in
      FVB/N mice. The intestinal lesions affect uniformly the cecum, colon, and rectum
      but not the small intestine. The elongation of the crypts is accompanied by an
      inflammation of the lamina propria and submucosa. Hepatic, renal, and pancreatic
      functions tested in clinical assays are within nonpathological range, suggesting
      that the major defect lies in colonic epithelial cells. Still, small but
      consistent elevation in the hepatic enzymes alanine (AST) and asparate (ALT)
      aminotransferase are observed, along with a 70% increase in spleen weight. No
      homozygous mouse line has been established, because of a markedly reduced
      fertility of the mK8-/- females. Previously, we reported that the mK8- targeted
      mutation causes embryonic lethality in (C57B1/6x129Sv) mice. This strong effect
      of the genetic background on the mK8- mutant phenotype emphasizes the importance
      of using several inbred mouse strains to reveal the polygenic contribution to
      mutant phenotypes. Our results demonstrate that genetic modifiers of K8/K18
      filament functions, with profound effects on embryogenesis and gut functional
      integrity, are differentially active in the FVB/N and C57B1/6 genetic
      backgrounds. More importantly, the increase in mK8-/- gut epithelial cell number,
      rather than cell disruption, contrasts with the known function of epidermal
      keratins in providing mechanical strength.

PMID- 7528158
TI  - Radiation therapy for subfoveal choroidal neovascular membranes in age-related
      macular degeneration. A pilot study.
AB  - BACKGROUND: The natural course of the visual acuity of age-related subfoveal
      choroidal neovascularisation (CNV) membranes is poor. Laser photocoagulation of
      subfoveal CNV is recommended if the patient is willing to accept a large decrease
      in visual acuity immediately after treatment. A large proportion of patients with
      subfoveal CNV do not meet the Macular Photocoagulation Study Group (MPS)
      guidelines for laser photocoagulation. The fact that so few patients meet these
      criteria makes further research into new treatment techniques warranted. Ionising
      radiation may prevent the proliferation of endothelial cells of newly formed
      subretinal capillaries and may induce obliteration of the aberrant new vessels.
      METHODS: In this study, the effect of radiation therapy on subfoveal CNV
      membranes was evaluated. Four groups of ten patients were treated with external
      beam radiotherapy (16-MV photons) on an area of 1 cm2 (macular region) using a
      lens-sparing technique and total doses of 8-24 Gy. The first group received 8 Gy
      in one fraction. The second, third and fourth groups received 12 Gy in 2
      fractions, 18 Gy in three fractions and 24 Gy in four fractions respectively. The
      studied parameters included best-corrected visual acuity and membrane size and
      leakage on the fluorescein angiogram. We included 17 occult and 23 classic CNV
      membranes as defined by the MPS, with a duration of less than 5 weeks at
      presentation. Complete ophthalmic examination including fluorescein angiography
      was performed before and 3, 12 and 18 months after radiation treatment. We
      analysed the angiogram using a standard overprojection sheet. The results
      concerning the visual acuity and fluorescein angiography (FA) were compared with
      the extensively published, natural course data. RESULTS: The first group
      (including three cases of occult CNV) received 8 Gy in a single fraction. In this
      group only four of ten patients had stable visual acuity and stable FA appearance
      after 21 months follow-up. The visual acuity and FA remained stable after 13.6
      months follow-up in seven of the patients in group 2 (12 Gy in two fractions,
      four occult CNV). The third group (18 Gy in three fractions, seven occult CNV)
      contained six patients with stable visual acuity, although two of them had CNV
      deterioration on the FA (11.1 months follow-up). In the last group (24 Gy in four
      fractions, three occult CNV), with a short follow-up of 5.6 months, eight
      patients had stable visual acuity and FA appearance. We did not note any
      regression of the CNV membrane on the angiogram. The visual acuity in groups 2, 3
      and 4 decreased to 0.1 or worse in only three cases, three cases and one case
      respectively after at least 6 months follow-up. CONCLUSION: Comparison of these
      findings with the natural history data of subfoveal age-related CNV suggests a
      beneficial effect of radiation therapy with a total dose of 12 Gy or more on the
      progression of CNV. To date no negative side effects have been observed.

PMID- 7528159
TI  - Tight junctions and paracellular permeability in cultured bovine corneal
      endothelial cells.
AB  - Intramembrane specializations of cultured bovine corneal endothelial cells were
      studied with thin section and freeze-fracture electron microscopy and related to
      the paracellular permeability and the transendothelial resistance (Rt) of the
      monolayers. The following intercellular junctions were found: single and
      discontinuous networks of tight junctions (TJ) which girdle the apico-lateral
      cell perimeter incompletely, gap junctions, and membrane undulations suggesting
      intermediate junctions. The macromolecular tracer ruthenium red penetrated into
      the lateral intercellular space beyond the level of the incomplete belt of TJ. Rt
      of these monolayers was 20.9 +/- 1.0 omega.cm2. Protamine induced a reversible
      increase of Rt to 118 +/- 5% of its control value. We conclude that incomplete
      belts of TJ may be the morphological counterpart of the high paracellular
      permeability of this monolayer and functionally and morphologically resemble
      those of their native endothelium. Cultured corneal endothelial cells are an
      excellent model for studying the influence of incomplete belts of TJ on
      paracellular permeability of cells.

PMID- 7528161
TI  - [Mutism and aphasia--a review of the literature].
AB  - Mutism in the sense of a complete inability to produce oral language is a rare
      symptom in aphasic disorders and most often occurs as a transient initial sign.
      Among the pathomechanisms causing muteness in aphasia, disturbances of speech
      initiation and of limbic aspects of speech production on the one hand and speech
      motor programming impairments on the other are considered. This article reviews
      clinical reports of extremely reduced speech or complete muteness in the context
      of aphasia, discussing the observed symptom patterns as well as their
      neuroanatomic correlates and aspects of their recovery.

PMID- 7528157
TI  - RNA localization along the anteroposterior axis of the Drosophila oocyte requires
      PKA-mediated signal transduction to direct normal microtubule organization.
AB  - Microtubule polarity has been implicated as the basis for polarized localization
      of morphogenetic determinants that specify the anteroposterior axis in Drosophila
      oocytes. We describe mutation affecting Protein Kinase A (PKA) that act in the
      germ line to disrupt both microtubule distribution and RNA localization along
      this axis. In normal oocytes, the site of microtubule nucleation shifts from
      posterior to anterior immediately prior to polarized localization of bicoid and
      oskar RNAs. In PKA-deficient oocytes, posterior microtubules are present during
      this transition, oskar RNA fails to accumulate at the posterior, and bicoid RNA
      accumulates at both ends of the oocyte. Similar RNA mislocalization patterns
      previously reported for Notch and Delta mutants suggest that PKA transduces a
      signal for microtubule reorganization that is sent by posteriorly located
      follicle cells.

PMID- 7528162
TI  - Alternating chemotherapy regimen (P-VABEC) for intermediate and high-grade non
      Hodgkin's lymphoma of the middle aged and elderly.
AB  - An intensive third generation regimen (P-VABEC) including adriamycin, etoposide,
      cyclophosphamide, vincristine, bleomycin and prednisolone was administered to 43
      unselected elderly patients with intermediate or high-grade non-Hodgkin's
      lymphomas (NHL). The median age was 67, 40 per cent were Ann Arbor stage IV, 73
      per cent had 'B' symptoms, 55 per cent had bulky disease, 48 per cent had serum
      lactate dehydrogenase greater than 450 U/l, 85 per cent had serum thymidine
      kinase greater than 4 U/l. Thirty patients were previously untreated. The
      complete remission (CR) rate was 74 per cent, and the partial remission (PR) rate
      23 per cent, with an overall response rate of 97 per cent. The regimen was
      carried out on an outpatient basis in all patients. No death occurred during
      therapy. The Kaplan-Meier actuarial survival of all patients at 3-years is 47 per
      cent, and 50 per cent (16/32) of all patients who attained CR remain alive and in
      remission at a median of 21+ months (range 6+ to 42+). These results confirm that
      high remission and failure-free survival rates can be achieved also in elderly
      unselected patients with aggressive NHL treated with curative intent.

PMID- 7528163
TI  - Intracytoplasmic eosinophilic hyaline globules in cartilaginous neoplasms: a
      surgical, pathological, ultrastructural, and electron probe x-ray microanalytic
      study.
AB  - Hyaline globules (HGs), spherical intracytoplasmic eosinophilic droplets, have
      been associated with a variety of conditions, including hepatocellular carcinoma,
      lung adenocarcinoma, and Kaposi's sarcoma, but they have not been described in
      cartilaginous tumors. In specimens of 60 cartilaginous neoplasms we found that 22
      of 33 chondrosarcomas (67%), eight of 16 enchondromas (50%), and three of seven
      soft tissue chondromas (43%) exhibited HGs. HGs were seen more commonly in low
      grade chondrosarcoma (70%) and were relatively rare in high grade chondrosarcoma
      (25%). No HGs were identified in three osteochondromas, one synovial
      chondromatosis, or 15 normal cartilaginous tissues taken from various sites.
      Cartilage associated HGs ranged in size from 2 to 20 microns, were diastase
      resistant and periodic acid-Schiff (PAS) stain positive, demonstrated
      autofluorescence, and variably stained with Mallory's phosphotungstic acid
      hematoxylin stain (PTAH). A panel of immunostains did not show any specific
      staining reactions with HGs. Ultrastructurally the HGs were spherical, non
      membrane-bound bodies having complex architectural features associated with
      profiles of rough endoplasmic reticulum. Electron probe x-ray microanalytic
      (EPXMA) study showed significant peaks of sulphur and calcium. We conclude that
      HGs represent secretory products of probable glycoprotein nature, may accumulate
      in a variety of cartilaginous neoplasms, and may be seen more frequently in low
      grade chondrosarcomas.

PMID- 7528165
TI  - Cytoplasmic inclusions in neocortical astrocytes associated with arteriopathic
      encephalopathy and dementia.
AB  - We describe what we believe to be the fifth case of a degenerative condition of
      the brain characterized by unusual intracytoplasmic inclusions in neocortical
      astrocytes, and we review four previous reports of what appears to be the same
      condition. Whereas these previous cases were characterized by prolonged clinical
      mental and psychomotor retardation, our case describes a rapid onset in a
      previously fit and mentally able patient in whom the astrocytic inclusions showed
      a close association with fibrohyaline vascular degeneration and changes
      resembling those of Alzheimer's disease. The inclusions, which were most frequent
      in the second to fourth layers of the frontal, temporal, and occipital cortices
      but absent from subcortical regions, consisted of large, irregular hyaline bodies
      surrounding the nucleus and extending into the proximal parts of cell processes.
      Ultrastructurally they consisted of free ribosomes in a granular and filamentous
      matrix. They were not bound by a membrane. Lipofuscin granules were associated
      with them. It is suggested that the inclusions might result from a disturbance of
      protein metabolism in protoplasmic astrocytes, but their true significance is
      unknown.

PMID- 7528164
TI  - Immunocytochemical study of epidermal growth factor receptor, transforming growth
      factor alpha, and "squamous differentiation" in human endometrial carcinoma.
AB  - The expression of epidermal growth factor receptor (EGFr) and transforming growth
      factor alpha (TGF-alpha) was compared with the presence of "squamous
      differentiation" (SD) visualized in various histotypes of endometrial carcinoma
      by using a panel of monoclonal antibodies. The results of the current study
      demonstrate that EGFr and TGF-alpha are present in routinely processed
      endometrial carcinoma. The highest positive EGFr and TGF-alpha expression was
      seen in the group of adenocarcinomas with SD. The more intense EGFr and TGF-alpha
      immunoreactivity was observed in "squamous" foci both in adenoacanthomas (AA) and
      in adenosquamous carcinomas (AS). These EGFr- and TGF-alpha-positive squamous
      areas prevalently displayed a "stratification-related" cytokeratin (CK)
      immunoprofile characterized by the expression of CKs 1, 4, 5, 10, 13, 14, and 16.
      No correlation was found between EGFr- and TGF-alpha-positive status and depth of
      myometrial invasion or surgical stage. These results clearly demonstrate that
      EGFr and TGF-alpha expression is related remarkably to endometrial carcinoma with
      "squamous" areas both morphologically and immunophenotypically. This specific
      association leads us to suggest that EGFr and TGF-alpha expression in endometrial
      carcinoma may be prevalently involved in the equilibrium of cell differentiation
      of the "squamous" foci commonly observed in this group of neoplasias.

PMID- 7528160
TI  - [Hypervolemic hemodilution as a means of preventing homologous blood transfusion.
      A simple alternative to acute normovolemic hemodilution].
AB  - PROBLEM: Acute normovolenic hemodilution (ANH) is timeconsuming and complicated,
      and has only a small effect in reducing the need for homologous blood. A simpler
      procedure is hypervolemic hemodilution (HHD). In the present prospective,
      randomized study, HHD is compared with ANH for its blood-saving effect. STUDY
      DESIGN: Forty-nine patients undergoing total hip replacement were admitted. Group
      I (ANH): Withdrawal of 15 ml/kg bodyweight autologous blood and isovolemic
      replacement by hydroxyethyl starch (200/0.5). Group II (HHD): Infusion of 15
      ml/kg bodyweight hydroxyethyl starch (200/0.5). RESULTS: No significant
      differences were found between the groups in terms of Hb, hematocrit and
      coagulation. The blood loss (intra-operative+drainage losses) was comparable in
      the two groups at 1274 +/- 310 ml (HHD) and 130 +/- 335 ml (ANH). During the
      period under investigation, 66% of the patients in the HHD group and 57% in the
      ANH group required no homologous blood. CONCLUSION: HHD is just as effective as
      ANH for reducing homologous blood requirements, and is much simpler to apply.

PMID- 7528167
TI  - Identification of four genes coding for isoforms of murinoglobulin, the monomeric
      mouse alpha 2-macroglobulin: characterization of the exons coding for the bait
      region.
AB  - Murinoglobulins are the single chain members of the alpha 2-macroglobulin family
      of proteinase inhibitors in the mouse. DNA clones representing the genes coding
      for four different murinoglobulins were isolated from three independent mouse
      genomic DNA libraries. Sequence analysis demonstrated that in each gene two exons
      are coding for the bait region. This is the specific protein sequence in each
      alpha-macroglobulin, which is functionally important since it is extremely
      sensitive to cleavage by different proteinases. The molecular data established
      the existence of at least four different murinoglobulin genes. Three of these
      corresponded to the three cDNA clones previously identified. Sequencing of intron
      exon boundaries and intron sizing allowed us to construct physical maps of the
      region from exon 15 to exon 25 (numbered in comparison to mouse alpha 2
      macroglobulin) in each murinoglobulin gene. Southern blotting of genomic DNA from
      five different mouse strains confirmed this analysis and even suggested the
      possible existence of a fifth murinoglobulin gene. These data indicate that the
      mouse presents a genetic repertoire of the alpha 2-macroglobulin family much more
      complex than originally anticipated. The bait region exon sequences showed a
      considerably higher degree of divergence (72 to 88% sequence identity) than that
      of the flanking exon sequences coding for adjacent, structural domains of the
      murinoglobulin proteinase inhibitors (91 to 96%). Even more surprising was that
      adjacent intron sequences are conserved as faithfully as the nonbait region
      coding exons (90 to 96%). These data demonstrate a unique property of the bait
      region coding sequences, as they apparently are allowed to mutate considerably.
      This divergency must then confer divergent proteinase inhibitory properties to
      the resulting proteins.

PMID- 7528168
TI  - Localization of murine macrophage inducible nitric oxide synthase to mouse
      chromosome 11.
AB  - There are at least three distinct nitric oxide (NO) synthase genes. Brain and
      endothelial NO synthases are constitutively synthesized, while NO synthase is
      inducible by cytokines in macrophages. We have utilized a backcross of (C57BL/6J
      x Mus spretus) x C57BL/6J to map the inducible NO synthase (Nos2). We report the
      chromosomal mapping of Nos2 to mouse chromosome 11, 3.3 cM proximal to Scya2.

PMID- 7528166
TI  - Molecular cloning of the mouse gene coding for alpha 2-macroglobulin and
      targeting of the gene in embryonic stem cells.
AB  - We have cloned the mouse gene coding for alpha 2-macroglobulin in overlapping
      lambda clones and have analyzed its structure. The gene contains 36 exons, coding
      for the 4.8-kb cDNA that we cloned previously. Including putative control
      elements in the 5' flanking region, the gene covers about 45 kb. A region of 3.8
      kb, stretching from 835 bases upstream of the cDNA start site to exon 4,
      including all intervening sequences, was sequenced completely. The analysis
      demonstrated that the putative promoter region of the mouse A2M gene differed
      considerably from the known promoter sequences of the human A2M gene and of the
      rat acute-phase A2M gene. Comparison of the exon-intron structure of all known
      genes of the A2M family confirmed that the rat acute phase A2M gene is more
      closely related to the human gene than to the mouse A2M gene. To generate mice
      with the A2M gene inactivated, an insertion type of construct containing 7.5 kb
      of genomic DNA of the mouse strain 129/J, encompassing exons 16 to 19, was
      synthesized. A hygromycin marker gene was embedded in intron 17. After
      electroporation, 198 hygromycin-resistant ES cell lines were isolated and
      analyzed by Southern blotting. Five ES cell lines were obtained with one allele
      of the mouse A2M gene targeted by this insertion construct, demonstrating that
      the position and the characteristics of the vector served the intended goal.

PMID- 7528169
TI  - A conserved epitope on nuclear pore phosphoproteins reflects cell division
      status.
AB  - The nuclear pore complexes mediate the selective nuclear import of proteins in a
      signal- and energy-dependent process. We have earlier reported the
      characterization of a monoclonal antibody, Mab E2, that recognizes a novel class
      of nuclear pore phosphoproteins involved in signal-binding and protein transport.
      In the present study, we have analyzed the pattern of immunoreactivity of Mab E2
      in cultured rat fibroblasts and have observed significant differences in the
      expression of epitopes in proliferating and quiescent cells. Furthermore, the
      common epitope recognized by Mab E2 is conserved across species, consistent with
      its essential role in nuclear protein import.

PMID- 7528171
TI  - Antigenic diversity and MHC genetics in sporozoite immunity.
AB  - A great deal of effort is directed towards developing a sporozoite vaccine. In
      the last decade, target antigens have been identified and cloned, and a number of
      vaccine trials undertaken in both humans and laboratory animals. One of the
      problems facing us is the lack of widespread immunogenicity of vaccine
      candidates. This relates, at least in part, to genetic factors in the vaccinee.
      Genes within the major histocompatibility complex (MHC) which restrict some
      sporozoite-specific responses have been identified. Antigenic diversity also
      contributes to the difficulty of developing a successful vaccine. This brief
      report provides some background information for these topics.

PMID- 7528170
TI  - Desensitization of IL-4 secretion from mouse bone marrow-derived mast cells.
AB  - Several recent findings indicate that mouse bone marrow-derived mast cells (BMMC)
      express RNA encoding interleukin-4 (IL-4) and secrete detectable amounts of IL-4
      in response to cross-linking of Fc epsilon RI receptors, Fc gamma R receptors, or
      to ionomycin. We investigated the desensitization of BMMC from the view point of
      both IL-4 secretion and histamine release. In a desensitization protocol, the
      cells were challenged with an optimal concentration of antigen (10 ng/ml of DNP33
      BSA) in the absence of calcium for various periods of time followed by addition
      of calcium to determine the loss in ability to release histamine or IL-4. In the
      context of histamine release, BMMC were desensitized completely in 45 min (T1/2
      approximately 5 min). By contrast, in the context of IL-4 secretion, BMMC were
      only partly desensitized (52 +/- 5% of the control response) after 1 h of
      desensitization. A longer-term (2-6 h) desensitization of BMMC did not result in
      complete inhibition of IL-4 secretion (44 +/- 5% of control after 6 h). Northern
      blot analysis showed that IL-4 mRNA accumulation was decreased after a 1 h
      desensitization (37% +/- 14% of non-desensitized cells), suggesting that
      desensitization of IL-4 release results from a decrease in the amount of mRNA
      accumulation. These and other data support the view that the IgE-mediated signal
      transduction cascade has meditor-specific pathways that are independently
      regulated by homeostatic mechanisms within mast cells.

PMID- 7528172
TI  - Epidemiological, clinical and biological characteristics of acute non-A, non-B
      hepatitis with and without hepatitis C virus infection.
AB  - Serially collected serum samples from 81 patients with acute non-A, non-B
      hepatitis were tested for the presence of antibodies to hepatitis C virus (anti
      HCV) by a second-generation enzyme immunoassay (EIA) test. Anti-HCV was detected
      in 56 cases (69%) during the first month, in 61 cases (75%) at 3 months and in 63
      cases (78%) at 6 months. In those 18 patients showing anti-HCV negative results
      in the three determinations, hepatitis C virus (HCV) RNA was tested using a
      nested polymerase chain reaction (PCR) in the first serum sample and was detected
      in only one case. Anti-HCV or HCV-RNA positive episodes were considered as acute
      hepatitis C, while those negative for both markers were classified as acute non
      A, non-B, non-C hepatitis. On comparing acute hepatitis C with the non-A, non-B,
      non-C episodes, no significant differences were found in the presence of
      jaundice, mean maximum alanine-aminotransferase (ALT) levels and positivity of
      markers of past hepatitis B virus (HBV) infection. However, patients with
      hepatitis C were significantly younger than those with non-A, non-B, non-C
      hepatitis (p = 0.002). Male sex (78.1% vs. 35.3%; p = 0.001), history of
      parenteral exposure (90.6% vs. 11.8%; p = 0.0001), and progression to chronicity
      (73.4% vs. 5.9%; p = 0.0001) were significantly more frequent in the HCV-related
      group. Although other possibilities cannot be excluded, these results suggest
      that there might be a different infectious agent implicated in the etiology of
      acute non-A, non-B, non-C hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528174
TI  - A discrete mathematical model applied to human basophil activation.
AB  - In this paper we present a model for the histamine negative feedback on the human
      basophil degranulation and another one for the feed-forward of these basophils on
      the extra-cellular histamine. These two models allow us to suggest a
      characterisation of the incubation time.

PMID- 7528175
TI  - A non-linear compartmental model of human basophil activation.
AB  - In this paper human basophil activation is modelled by means of a system of
      differential equations. The resolution of this system allows the justification of
      the incubation period and the unwedging period existing between the human
      basophil degranulation and the liberation of histamine.

PMID- 7528173
TI  - Successful treatment of a Trichosporon beigelii septicemia in a granulocytopenic
      patient with amphotericin B and granulocyte colony-stimulating factor.
AB  - Invasive fungal infections have become an increasing problem in severely
      immunocompromised hosts. We here report a case of septicemia, caused by
      Trichosporon beigelii, an unusual pathogen of systemic infections. This infection
      was acquired during a period of severe neutropenia after chemotherapy for
      relapsed acute myelogenous leukemia following allogeneic bone marrow
      transplantation. The patient recovered from a life-threatening T. beigelii
      septicemia due to early intensified treatment with amphotericin B and a rapid
      neutrophil recovery, enhanced by granulocyte colony-stimulating factor (G-CSF).
      According to the current literature, amphotericin B is the treatment of choice
      for systemic T. beigelii infections. In patients with severe granulocytopenia,
      the rapid recovery of neutrophils remains the most important factor for the
      outcome of this infection.

PMID- 7528176
TI  - Quantitative studies of fly visual sustained neurons.
AB  - We present a quantitative study of a neural network model [1] proposed for the
      sustained neurons in the fly visual system. Electrophysiological recordings of
      sustained neurons [2] are digitized and transferred to a computer. A numerical
      ordinary differential equation solver is used to simulate the model. In order to
      obtain an initial set of parameters, we introduce approximations to the model and
      obtain fits to parts of the response characteristics. These initial parameter
      values are then refined by optimization routines. The model is compared to data
      in 4 different experimental paradigms and in general is in good agreement with
      data. We conclude that the simplified versions of temporal and spatial adaptation
      mechanisms of the model capture the essential features of the dynamics of
      sustained neurons and that the refinement of the model requires further
      experimental studies to elucidate the number of stages involved in temporal
      adaptation as well as the precise shape of the relationship between the membrane
      potentials and the spike frequency for the sustained neurons.

PMID- 7528177
TI  - Obstructive prostatic symptoms: a community survey in Jerusalem.
AB  - BACKGROUND: Benign prostatic hypertrophy has a high prevalence in men aged > or =
      50, but there is little information on the correlates of obstructive symptoms.
      METHODS: The prevalence and correlates of reported prostatic symptoms in men aged
      > or = 50 years were studied in a community survey in the Kiryat Hayovel
      neighbourhood of Jerusalem in 1985-1987. Five prostate-related questions were
      asked. Two indices of emotional health were used: the Psychiatric Epidemiology
      Research Interview demoralization scale and a scale based on the Cornell Medical
      Index. Associations with sociodemographic, behavioural, emotional, biochemical
      and physical variables and with self-appraised health were examined both
      controlling for age only and by multivariate logistic regression. RESULTS: The
      prevalence rates in the 839 respondents were 20.4% for hesitancy, 41.1% for weak
      stream, and 26.7% for terminal dribbling; the rates tended to increase with age.
      The associations between the symptoms (controlling for age) were significant, the
      strongest being between hesitancy and weak stream. All three of the urinary
      symptoms were associated with indices of emotional distress. In the multivariate
      analysis, the odds ratios when men in the highest and lowest quartiles of
      emotional ill health were compared were 3.0 for hesitancy, 2.2 for weak stream,
      and 3.8 for dribbling. Specific symptoms were associated with blood pressure,
      social class and educational level. CONCLUSION: The striking associations with
      emotional ill health underline the importance of appropriate attention to the
      emotional health of patients who complain of prostatic symptoms.

PMID- 7528178
TI  - The effect of extracorporeal shock wave lithotripsy on pancreatic enzymes.
AB  - In order to assess the effect of electromagnetic shock waves on pancreatic
      tissue, we studied serum and urinary amylase and serum lipase levels prior to, 1
      hour, 1 day and 1 week after extracorporeal shock wave lithotripsy (ESWL) in 150
      patients with upper urinary tract stones. A control group consisted of 22
      patients with lower ureteric stones who underwent ESWL. All three parameters
      increased after ESWL (p < 0.001); however, this increase was within normal
      laboratory limits. There was no difference between the right and left renal
      units. In the control group there was no change of pancreatic enzymes after ESWL.
      High energy shock waves may cause some elevations of pancreatic enzymes, probably
      due to altered cell membrane permeability, however, ESWL with an electromagnetic
      shock wave emitter system does not cause significant injury to the pancreatic
      tissue.

PMID- 7528179
TI  - Quantitative-comparative histology of prostatic adenomas in medically and
      surgically treated patients.
AB  - Transvesical adenectomy was done in 60 men with prostatic adenomas, including 40
      pretreated medically (20 with prazosin, 20 with Tadenan). The resected material
      was sampled for histologic examination. Glandular, smooth muscle and fibrotic
      tissues as well as inflammatory foci were assessed quantitatively by planimetry.
      No adenomas consisting solely of glandular hyperplasia were found. In adenomas
      from patients pretreated with prazosin smooth muscle tissue was predominant and
      postinflammatory lesions were the least frequently observed. In Tadenan
      pretreated patients quantitative predominance of glandular and fibrotic tissues
      was found and smooth muscle constituted the smallest part of the adenomas.
      Patients who had undergone surgery only had adenomas in which focal inflammation
      predominated.

PMID- 7528180
TI  - Is modified retroperitoneal lymph node dissection (MRLND) still feasible in the
      treatment of patients with clinical stage I non-seminomatous testicular cancer?
AB  - The results of treatment by means of modified RLND in 52 patients with clinical
      stage I non-seminomatous testicular cancer are presented. Retroperitoneal lymph
      node metastases were found in 15 patients (28.8%) with clinical stage I (CS-I)
      diagnosed prior to surgery. They received chemotherapy according to PVB schedule.
      Ejaculation disturbances persisted in 4 patients (7.7%). Relapses occurred in 4
      patients (7.7%) from the group without lymph node metastases, and complete
      remission occurred after adjuvant PVB chemotherapy. All patients are still alive.
      Among the analysed factors which might favour development of metastases, only
      neoplastic invasion of the blood vessels of the primary tumour was statistically
      significant. In the authors' opinion MRLND may still be used as a diagnostic and
      therapeutic method in clinical stage I non-seminomatous testicular cancer besides
      "watch policy" or primary chemotherapy.

PMID- 7528181
TI  - Association of a choroidal ganglion cell plexus with the fovea centralis.
AB  - PURPOSE: After recently demonstrating an NADPH-diaphorase-, nitric oxide synthase
      (NOS)-positive ganglion cell plexus in the human choroid that was absent in
      rabbit and rat eyes, the authors extended their comparative studies to nonhuman
      primates and to subprimate mammals. METHODS: The authors investigated the
      choroids of diurnal cynomolgus monkeys with well-developed fovea centralis and
      accommodative systems; diurnal tree shrews without a fovea centralis or
      accommodative capacity; nocturnal owl monkeys with substantial accommodative
      capacity but without a fovea centralis; cats with an area centralis but no fovea
      centralis; and pigs without an area centralis or a fovea centralis. The latter
      two species have moderately developed ciliary muscles. Wholemounts of the choroid
      of eight cynomolgus monkey, two owl monkey, four tree shrew, four cat, and four
      pig eyes were stained for NADPH-diaphorase. In addition, frozen sections through
      the cynomolgus monkey choroid were stained for NOS and vasoactive intestinal
      polypeptide (VIP). RESULTS: In all species, the choroidal vessels were surrounded
      by NADPH-diaphorase-positive nerve fibers. A ganglion cell plexus, however, was
      seen only in cynomolgus monkey eyes. The ganglion cells stained for NOS and VIP.
      CONCLUSIONS: The presence of intrachoroidal nitrergic nerve cells restricted to
      species with a fully developed fovea centralis may indicate a functional
      correlation of these structures.

PMID- 7528182
TI  - Hyaluronan in the bovine ocular anterior segment, with emphasis on the outflow
      pathways.
AB  - PURPOSE: It has been postulated that glycosaminoglycans play a role in the
      regulation of outflow resistance. The purpose of these studies was to localize
      the distribution of hyaluronan (HA) in the anterior segments of bovine eyes to
      understand better the possible role of HA in the outflow pathway. METHODS: Eyes
      from four 2-week-old calves and four 1-year-old cows were examined using a
      biotinylated-hyaluronan binding protein to localize HA in tissue sections of the
      anterior segment of bovine eyes. Various fixations and microwave irradiation were
      compared. The vitreous body in each section served as a positive control.
      Sections treated with Streptomyces hyaluronidase were used to confirm
      specificity. RESULTS: No significant difference in distribution of HA was found
      between various fixations and between calves and cows. HA was found in
      subconjunctival connective tissue and in intercellular spaces of limbal and
      conjunctival epithelium, but not in corneal epithelium. Staining was sometimes
      found on the surface of the corneal epithelium and endothelium, as well as on the
      conjunctival epithelium. No staining was found within the corneal stroma. There
      was HA in iris stroma, but not in the root of the iris or ciliary body stroma. HA
      was present in the anterior, nonfiltering part of the trabecular meshwork (TM)
      and surrounding collector channels and blood vessels in the sclera; to a lesser
      extent, it was present in the juxtacanalicular region of the TM. HA was
      detectable neither within trabecular beams nor filling the intertrabecular
      spaces. Strong staining was found, however, in the nerve bundles in the angle
      region. Staining for HA in vitreous was invariably positive, and in Streptomyces
      hyaluronidase-treated sections it was negative. CONCLUSION: HA was not uniformly
      distributed in the bovine TM. The distribution of HA in the flow pathway of the
      aqueous outflow system indicates that only a small fraction of the HA found in
      biochemical analyses of the bovine meshwork is located in the region where the
      flow resistance is thought to reside.

PMID- 7528183
TI  - Trends in pain therapy.

PMID- 7528184
TI  - Intrathecal morphine in the treatment of chronic intractable pain.
AB  - Fifteen patients with intractable pain received intrathecal morphine delivered
      via a programmable (Medtronic) device. In twelve patients the pain was due to
      cancer and three patients had pain of non malignant origin. All of the patients
      reported excellent or good relief. A total of 14 complications were reported in 7
      patients. Most of these were minor and related to surgical or mechanical
      problems. One patient with pain of non malignant origin developed serious
      complications which required the removal of the infusion device. The results of
      this study show that chronic intrathecal infusion of morphine is superior to
      conventional forms of analgesia in patients with intractable pain of malignant
      origin. We would advise that it should remain a therapy of last resort in
      patients with intractable non malignant pain as the long term side effects are
      still unknown and the potential for serious side effects still exists.

PMID- 7528186
TI  - [Distal edema and hyperhidrosis of the arm. Symptoms of reflex sympathetic
      dystrophy (Sudeck's disease)].
AB  - Reflex sympathetic dystrophy is characterized clinically by the triad of
      autonomic sympathetic dysfunction, and motor and sensory disturbances of the
      affected extremity. Typical symptoms are distal generalized edema with cyanotic
      skin, pathologic function of eccrine sweat glands and diffuse dull pain. If
      reflex sympathetic dystrophy is not recognized an irreversible stage may be
      reached, with atrophic pale, cool, and anhidrotic skin, contractures and diffuse
      osteoporosis. The syndrome can be idiopathic but can also be precipitated by a
      variety of factors, including banal trauma, bone fracture, and traumatic nerve
      lesions. Pathophysiologically, a functional disturbance of sympathetic nerve
      fibres may result in a vicious circle of blood flow dysfunction, excitation of
      afferent nociceptors and maintenance of sympathetic dysfunction at the level of
      the spinal or central nervous system. In the patient presented in this paper,
      sympathetic dysregulation of reflex sympathetic dystrophy was cured by means of
      blockades of the stellate ganglion.

PMID- 7528185
TI  - Improvement of the T-cell response to a non-immunogenic peptide by its tandem
      association with a highly efficient T-helper peptide.
AB  - The 45-69 peptide, an helper T-cell epitope derived from HIV nef protein, is
      strongly immunogenic. A T-cell proliferative response was observed following
      immunization of Lou/M rats with 45-69 peptide administered in low dose and
      without any adjuvant. It is already known that the T-cell response to the 115-131
      peptide of Sm28GST antigen, a protein of the parasite Schistosoma mansoni,
      requires the presence of a carrier or the use of peptidic constructs. We
      demonstrate here that a T-cell response against the 115-131 peptide can be
      obtained in the absence of adjuvant using peptidic constructs (115-45 and 45-115
      peptides) resulting from tandem synthesis of 115-131 and 45-69 peptides. A
      covalent association of both peptides is necessary, since the co-injection of 45
      69 and 115-131 peptides is not sufficient to induce a detectable anti-115-131 T
      cell response. The mutual orientation between the respective tandem peptides (45
      115 and 115-45) is critical for the T-cell response. These peptidic constructs
      possess distinct properties of antigenicity and immunogenicity but both allowed
      to reveal the existence of a 115-131 specific T-cell response normally
      undetectable using 115-131 peptide alone. This immunopharmacological approach
      should be useful in the rational design and construction of vaccines.

PMID- 7528188
TI  - Stimulation of T cells via CD44 requires leukocyte-function-associated antigen
      interactions and interleukin-2 production.
AB  - This article reports the results of the analysis of the activation signals
      delivered to T and B cells by means of the CD44 molecule and an agonistic mAb,
      i.e., CB05 mAb, which is able to induce cell activation and aggregation upon
      binding. The functional effects culminate in T-cell proliferation in the presence
      of autologous accessory cells. Such effects are barely detectable in thymocytes,
      while B cells prove refractory to the action of the agonistic mAb. All of these
      events have been followed by the expression of surface activation markers, by the
      transcription of selected cytokine genes (IFN-gamma, IL-4, and GM-CSF), and by
      the secretion of IL-2. Cell activation via CD44 has been evaluated as to its
      relationship with CD3 and CD2 activation pathways, proving synergistic with the
      latter. The CD44 signaling is protein kinase dependent. Furthermore, the role of
      surface molecules as cosignals in the CD44 pathway has been analyzed, showing
      that CD11a (and its ligand CD54), HLA class I, and CD25 are instrumental in the
      implementation of (a) efficient activation/proliferation signals and (b) a potent
      cytotoxic potential.

PMID- 7528189
TI  - Inflamed joints of patients with rheumatoid arthritis contain T cells that
      display in vitro proliferation to antigens present in autologous synovial fluid.
      Functional analysis on the basis of synovial-fluid-reactive T-cell clones and
      lines.
AB  - The immunopathology of inflamed joints in patients with RA is thought to result
      from an antigen-driven T-cell response. The antigen(s) responsible for the
      activation of synovial T cells, however, are as yet unidentified. In this study,
      we tested SF as a potential source of (auto)antigen(s). Five of 15 IL-2-expanded
      T-cell lines generated from SF cells of RA patients displayed a proliferative
      response to autologous SF. Five CD4+CD8-alpha beta TCR+SF-reactive T-cell clones
      obtained from responder T-cell lines were studied in more detail. Three T-cell
      clones from one RA patient were found to recognize epitopes in autologous SF in
      the context of DR4(Dw4), and two T-cell clones of another RA patient responded to
      autologous SF in the context of the HLA-DPB1*0401 gene product. The two DP
      restricted clones and one of the DR-restricted clones did not proliferate to 50
      SF samples of other RA patients, whereas the remaining DR-restricted clones
      responded to one allogeneic sample. Sequence analysis demonstrated that the
      latter clones expressed identical V beta 6.9 + TCR beta chains. This was also
      found for the (V beta 19+) DP-restricted clones. Proliferation of SF-reactive T
      cells was not only obtained with SF of the joint that had contained the T cells,
      but also with autologous SF of other affected joints. Together, these findings
      indicate that epitopes able to stimulate synovial T cells differ among RA
      patients, but may be similar within multiple joints of an individual patient. The
      presence of T cells able to respond to SF antigens in inflamed joints suggests
      that these T cells play an active role in the pathogenesis of RA.

PMID- 7528187
TI  - [Drug therapy of acute inner ear hearing loss in childhood and adolescence].
AB  - Sensorineural hearing loss in early childhood may severely interfere with normal
      speech and language development. This by itself requires pursuit of an effective
      therapeutic procedure. Here we report the results of therapy with a rheological
      agent and procaine-HCl with or without the addition of steroids. Immunological
      testing was also studied for possible circulating antibodies in sera of affected
      children. Retrospective analysis of therapeutic results showed that the
      therapeutic procedure employed may be beneficial, since hearing improved
      considerably in some cases. Since an autoimmune-related sensorineural hearing
      loss has been postulated for some years, results presented here could be used as
      an argument for the presence of antibody-related inner ear disorders in early
      childhood. These findings suggest that circulating antibodies in children
      suffering from sensorineural hearing losses produce an inflammatory process
      involving inner ear structures. Circulating antibodies may also indicate a
      secondary immune reaction. However, sensory hearing loss occurring in early
      childhood may be steroid sensitive.

PMID- 7528190
TI  - Different regions of the N-terminal domains of HLA-DR1 influence recognition of
      individual peptide-DR1 complexes.
AB  - The contributions of individual amino acids in the polymorphic beta chain and the
      conserved alpha chain of HLA-DR1 to influenza HA-specific DR1-restricted and anti
      DR1 allospecific T-cell recognition were analyzed. The genes encoding HLA-DR1
      were subjected to site-directed mutagenesis in order to introduce single amino
      acid substitutions at 12 positions in the beta 1 domain and 11 positions in the
      alpha 1 domain. The beta 1-domain substitutions were all at polymorphic positions
      and introduced residues that are found in DR4 alleles. The amino acids introduced
      into the DR alpha 1 domain were based on the sequences of other human and mouse
      class II alpha chains. The responses of 12 DR1-restricted T-cell clones specific
      for two peptides of HA and seven anti-DR1 allospecific clones were studied.
      Substitutions at positions that point up from and into the peptide-binding site
      in the third variable region of the beta 1-domain alpha-helix caused substantial
      reduction in the responses of all of the clones. Substitutions at multiple
      positions in the beta 1-domain floor and in the alpha 1 domain influenced the
      anti-DR1 responses of the alloreactive and of the HA100-115-specific T-cell
      clones. In contrast, very few changes outside of the beta 1 domain third variable
      region affected the responses of the HA306-324-specific DR1-restricted T-cell
      clones. These results suggest that a surprisingly limited region of the HLA-DR1
      molecule is critically involved in T-cell recognition of HA306-324 by DR1
      restricted T cells. However, the susceptibility of the HA100-115-specific and the
      anti-DR1 allospecific T-cell clones to substitutions at multiple positions in
      both N-terminal domains shows that the response to DR1-HA306-324 is unusual and
      may reflect the promiscuity with which this peptide binds to HLA-DR molecules.

PMID- 7528191
TI  - WIN 66306, a new neurokinin antagonist produced by an Aspergillus species:
      fermentation, isolation and physico-chemical properties.
AB  - WIN 66306 (1a), a cyclic peptide containing a novel amino acid, was isolated as a
      neurokinin antagonist from an Aspergillus species, labelled SC230. Conditions
      that maximized the production of 1a were developed, leading also to production of
      the related compound WIN 68577 (2) and rosellichalasin (3). Both 2 and 3 were
      more active in the rat NK1 than in the human NK1 receptor binding assay, while 1a
      was more active at the human receptor with an inhibitor affinity constant of 7
      microM.

PMID- 7528192
TI  - Effects of dietary fiber on intestinal growth, cell proliferation, and morphology
      in growing pigs.
AB  - Growing pigs (initial BW 14.3 +/- 1.2 kg) were fed isocaloric (3.26 Mcal of
      ME/kg) and isonitrogenous (16% CP) diets containing either 0 (low fiber, LF; n =
      4) or 10% (high fiber, HF; n = 4) wheat straw for ad libitum intake for 14 d. On
      d 14, each pig was injected i.v. with bromodeoxyuridine (BrdU, a thymidine
      analog; 5 mg/kg) and was slaughtered 1 h later. Visceral organs (liver, pancreas,
      and intestines) were weighed, and tissue samples were obtained. Feed consumption,
      daily gain, gain: feed, and final BW did not differ between treatments. Neither
      visceral weights nor visceral weights per unit of eviscerated BW were affected by
      diets. Tissue concentrations of DNA (milligrams/gram of tissue) were lower (P <
      .03) in HF than in LF only for jejunum, ileum, and liver. Contents of DNA and
      protein (milligrams) did not differ between LF and HF for intestinal segments or
      liver. Content of RNA (milligrams) was greater (P < .04) in HF than in LF only
      for colon. The number of crypt cell nuclei that were labeled with BrdU
      (indicating DNA synthesis and thus cell proliferation) was increased (P < .03) in
      HF relative to LF for jejunum and colon. The number of epithelial cells
      exhibiting DNA fragmentation (indicating programmed cell death) was greater (P <
      .07) in the HF than in the LF group for jejunum and ileum. Width of intestinal
      villi was increased (P < .10) in HF vs LF for jejunum and ileum. Depth of
      intestinal crypts was increased (P < .08) in HF vs LF for jejunum, ileum, and
      colon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528193
TI  - Growth and development of bovine fetuses and neonates representing three
      genotypes.
AB  - Growth was examined in bovine fetuses and neonates that typically differ in
      mature size and postnatal developmental pattern. Pregnancies were established
      from matings expected to produce early (E), late (L), and intermediate (I)
      maturing postnatal growth patterns. Tissues were collected at 100 and 200 d of
      gestation and 30 d postnatal. Muscle:body weight ratios were lower at 100 and 200
      d for the E maturity type than for the L maturity type (P < .05). This differs
      from observations of muscle:body weight ratios made at 30 d postnatal, at which
      time ratios for E were either greater than (triceps brachii, P < .05) or similar
      to those for L. Few differences due to maturity type were observed at 100 d for
      bone weight:body weight ratios; however, at 200 d of gestation E bone weight:body
      weight ratios were generally lower (P < .05) than those for L. The genotypic
      relationship for bone weight:body weight ratio at 30 d postnatal was similar to
      that observed at 200 d of gestation. Observations of organ weight:body weight
      ratios revealed no clear patterns due to maturity type. The genotypic
      relationship for total muscle DNA content was similar to that observed for muscle
      weight. These results indicate that fetal muscle development differs in cattle
      that have different postnatal growth patterns by as early as 100 d of gestation
      and that differences in fetal muscle growth are related to differences in muscle
      hyperplasia.

PMID- 7528194
TI  - Dietary energy restriction-mediated growth and mammary development in rats.
AB  - This research examined the extent to which dietary energy restriction modulates
      growth and mammary tissue composition during different developmental stages.
      Female rats were assigned to the following three dietary treatments: 1) ad
      libitum access to feed (AL), 2) 30% continuous energy restriction (CER), and 3)
      stair-step energy restriction (SSER). The SSER treatment consisted of an 8-wk,
      alternating schedule beginning with 60% energy restriction for 2 wk, followed by
      realimentation to feed offered for ad libitum intake for 2 wk. All treatments
      were initiated when rats were 5 wk of age. After the stair-step regimen, SSER
      rats were maintained on a 30% energy-restricted diet for the duration of the
      experimental period (25 wk of age). Rats reared on the energy restriction
      regimens weighed less and consumed less (P < .05) feed than controls, but they
      had feed efficiencies similar to those of controls. Energy restriction delayed
      the onset of puberty and retarded the growth of the offspring but had no effect
      on litter size. The overall values (averaged pregnancy through involution stages)
      of DNA, RNA, and RNA: DNA ratio (based on fat-free DM) and protein concentrations
      were similar in the mammary tissues of the energy restriction groups and those of
      the AL group. Lipid content in mammary tissue was generally decreased in the CER
      and SSER groups compared with the AL group. In summary, energy restriction
      delayed the onset of puberty and retarded the growth of the dam and progeny, but
      it did not affect mammary cellularity as it reduced fat deposition in the mammary
      gland.

PMID- 7528196
TI  - Production of monoclonal antibodies against Xanthomonas campestris pv.
      mangiferaeindicae and their use to investigate differences in virulence.
AB  - Four Xanthomonas campestris pv. mangiferaeindicae isolates from mango black spot
      lesions were grouped according to differences in virulence and used to raise
      monoclonal antibodies (mAbs). Two immunization approaches were followed. In the
      first, four groups of mice were immunized, each with a different isolate and the
      spleens from each group homogenized together for cell fusion. The second approach
      entailed immunization of a single group of mice with bacteria pooled from all
      four isolates. The resultant mAbs were characterized with regard to the antigen
      binding specificity and antibody class. A relationship between mAb binding
      specificity and virulence of the bacteria was shown by Western blot analysis.

PMID- 7528195
TI  - Administration of porcine somatotropin by a sustained-release implant: effect on
      follicular growth, concentrations of steroids and insulin-like growth factor I,
      and insulin-like growth factor binding protein activity in follicular fluid of
      control, lean, and obese gilts.
AB  - Prepubertal gilts of control (n = 30), obese (n = 30), or lean (n = 29) genetic
      lines were implanted with no, one, or two implants of porcine somatotropin (pST,
      each delivers 2 mg/d) for 6 wk starting at 160 d of age to determine whether pST
      affects ovarian function. At 4 mg/d, pST increased (P < .01) numbers of 4.0- to
      6.9-mm (medium) follicles but not (P > .10) numbers of 1.0- to 3.9-mm (small)
      follicles per gilt. Both doses of pST increased (P < .01) serum and follicular
      fluid (FFL) concentrations of IGF-I and activity of IGF binding protein (IGFBP)-3
      and 36-kDa IGFBP in all three lines; IGFBP-3 was the predominant IGFBP. In
      comparison, binding activity of IGFBP-2 was decreased (P < .01) in serum by 4 mg
      of pST but increased (P < .05) in FFL by 4 mg of pST. Lean gilts had lower (P <
      .05) serum concentrations of IGF-I and less (P < .05) total binding activity of
      IGFBP than control and obese gilts. Concentrations of estradiol in FFL of small
      and medium follicles tended (P < .08) to be increased by 2 mg/d of pST, whereas
      FFL concentrations of progesterone were unaffected by pST. Obese and control
      gilts had twofold greater (P < .05) FFL progesterone concentrations than lean
      gilts. We conclude that sustained-release implants of pST can stimulate
      follicular growth, increase concentrations of IGF-I in serum and FFL, and
      increase IGFBP activity in serum of genetically divergent lines of gilts without
      an adverse effect on ovarian function.

PMID- 7528197
TI  - Interaction of thyroid hormone and functional overload on skeletal muscle
      isomyosin expression.
AB  - This study examined the interaction of exogenous thyroid hormone 3,5,3'
      triiodothyronine (T3) and functional overload on skeletal muscle myosin heavy
      chain (MHC) expression, studied at both the protein and mRNA level of analysis.
      Animals were allocated to the following groups: 1) normal control, 2) overload
      control, 3) hyperthyroid control, and 4) hyperthyroid+overload. Overload of the
      rat plantaris was accomplished by surgical removal of its synergists (soleus and
      gastrocnemius), and the animals were made hyperthyroid by injections of T3 (350
      micrograms/kg every other day). After overload of 8 wk, muscle enlargement
      occurred by 53% for both overload groups (P < 0.05). This was accompanied by a
      330 and 82% increase in the relative content of type I and IIa MHC, respectively,
      and a corresponding decrease by 16 and 44% in type IIx and IIb MHC, respectively,
      in the overload control group (P < 0.05 vs. normal control). Changes in the
      relative and absolute content of mRNA for these MHCs paralleled the protein
      response. Exogenous T3 completely reversed the upregulation of type I MHC and the
      downregulation of type IIx associated with overload at both the protein and mRNA
      level (P < 0.05). However, T3 was only partially effective in blunting the
      downregulation of IIb MHC and the upregulation of IIa MHC (protein and mRNA)
      accompanying the overload.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528198
TI  - Cloning of the hsp70 (dnaK) genes from Rhizobium meliloti and Pseudomonas
      cepacia: phylogenetic analyses of mitochondrial origin based on a highly
      conserved protein sequence.
AB  - The genes for hsp70 (or dnaK) have been cloned and sequenced from Rhizobium
      meliloti and Pseudomonas cepacia, two bacterial species belonging to the alpha-
      and beta-subdivisions of gram-negative proteobacteria, respectively. On the basis
      of global alignment of HSP70 proteins, several sequence signatures have been
      identified that are distinctive of mitochondrial homologs and gram-negative
      proteobacteria on the one hand and the chloroplasts and cyanobacteria on the
      other. Detailed phylogenetic analyses of HSP70 sequences from various eubacteria
      and eukaryotic organellar and cytosolic homologs support the inference regarding
      the origin of mitochondria from a member of the alpha-proteobacteria and of
      chloroplasts from cyanobacteria. The analysis presented here also suggests a
      monophyletic origin of the mitochondrial homologs.

PMID- 7528199
TI  - Transcriptional control of dacB, which encodes a major sporulation-specific
      penicillin-binding protein.
AB  - Sporulation-specific sigma factor E (sigma E) of Bacillus subtilis is both
      necessary and sufficient for transcription of the dacB gene, which encodes
      penicillin-binding protein 5*. Evidence in support of this conclusion was
      obtained by primer extension analysis of dacB transcripts and the induction of
      active sigma E with subsequent synthesis of PBP 5* in vegetative cells.

PMID- 7528202
TI  - The role of ribonuclease H in multicopy single-stranded DNA synthesis in retron
      Ec73 and retron-Ec107 of Escherichia coli.
AB  - Bacterial reverse transcriptase is responsible for the synthesis of multicopy
      single-stranded DNA (msDNA). Reverse transcriptases from retron-Ec73 and retron
      Ec107 do not contain an RNase H domain. Cellular RNase H is therefore considered
      to be required to make the mature form of msDNA. We found that RNase HI, but not
      RNase HII, is required for the production of the mature form of both msDNAs.

PMID- 7528200
TI  - An epitope of elongation factor Tu is widely distributed within the bacterial and
      archaeal domains.
AB  - A monoclonal antibody (MAb), MAb 900, which detects a 43-kDa protein present on
      Escherichia coli was found. Subsequently, more than 90 organisms, belonging to
      either the bacterial, archaeal, or eucaryal domain, were tested for reactivity to
      this MAb. Of the bacterial and archaeal domains, almost all species proved to be
      positive, whereas all organisms from the eucaryal domain gave negative results.
      The 43-kDa protein was purified by affinity chromatography and subsequently
      analyzed by microsequencing methods. Two peptide sequences which showed a high
      degree of homology (> 99%) to the prokaryotic elongation factor Tu (EF-Tu) were
      obtained. Western blot (immunoblot) analysis using both purified EF-Tu and EF-Tu
      domains confirmed that the unknown protein was EF-Tu. The panbacterial
      distribution of EF-Tu, which is present in large amounts in every prokaryotic
      cell, renders this protein a good candidate for a diagnostic approach. In
      consequence, we have used the anti-EF-Tu MAb 900 to design both a dot blot assay
      and an enzyme-linked immunosorbent assay. From either blood culture, urine, or
      gall-bladder fluid, bacterial contamination could be detected. The sensitivity of
      these tests is currently 10(4) bacteria per ml.

PMID- 7528201
TI  - In vivo restriction by LlaI is encoded by three genes, arranged in an operon with
      llaIM, on the conjugative Lactococcus plasmid pTR2030.
AB  - The LlaI restriction and modification (R/M) system is encoded on pTR2030, a 46.2
      kb conjugative plasmid from Lactococcus lactis. The llaI methylase gene,
      sequenced previously, encodes a functional type IIS methylase and is located
      approximately 5 kb upstream from the abiA gene, encoding abortive phage
      resistance. In this study, the sequence of the region between llaIM and abiA was
      determined and revealed four consecutive open reading frames (ORFs). Northern
      (RNA) analysis showed that the four ORFs were part of a 7-kb operon with llaIM
      and the downstream abiA gene on a separate transcriptional unit. The deduced
      protein sequence of ORF2 revealed a P-loop consensus motif for ATP/GTP-binding
      sites and a three-part consensus motif for GTP-binding proteins. Data bank
      searches with the deduced protein sequences for all four ORFs revealed no
      homology except for ORF2 with MerB, in three regions that coincided with the GTP
      binding motifs in both proteins. To phenotypically analyze the llaI operon, a 9.0
      kb fragment was cloned into a high-copy-number lactococcal shuttle vector,
      pTRKH2. The resulting construct, pTRK370, exhibited a significantly higher level
      of in vivo restriction and modification in L. lactis NCK203 than the low-copy
      number parental plasmid, pTR2030. A combination of deletion constructions and
      frameshift mutations indicated that the first three ORFs were involved in LlaI
      restriction, and they were therefore designated llaI.1, llaI.2, and llaI.3.
      Mutating llaI.1 completely abolished restriction, while disrupting llaI.2 or
      llaI.3 allowed an inefficient restriction of phage DNA to occur, manifested
      primarily by a variable plaque phenotype. ORF4 had no discernible effect on in
      vivo restriction. A frameshift mutation in llaIM proved lethal to L. lactis
      NCK203, implying that the restriction component was active without the
      modification subunit. These results suggested that the LlaI R/M system is unlike
      any other R/M system studied to date and has diverged from the type IIS class of
      restriction enzymes by acquiring some characteristics reminiscent of type I
      enzymes.

PMID- 7528204
TI  - Expression of gangliosides GM3 (NeuAc) and GM3 (NeuGc) in myelomas and hybridomas
      of mouse, rat, and human origin.
AB  - In this study gangliosides from various myelomas and hybridomas of mouse, rat,
      and human origin were characterized by thin-layer and high-performance liquid
      chromatography, immunological methods (overlay technique) and fast atom
      bombardment mass spectrometry. Exclusively GM3 substituted with C24:1- and C16:0
      fatty acid, was found in all B cell-derived cell lines. C18 sphingosine was the
      single long chain base in each GM3 ceramide portion. The mouse myeloma (NS-1) and
      all hybridomas, obtained by fusion of mouse, rat, or human B lymphocytes with
      murine myelomas, showed high GM3 (NeuGc) content (> 75%) and low GM3 (NeuAc)
      expression. Absolute amounts of GM3 ranged from 0.2 up to 0.8 mg x 10(-9) cells.
      Normally, human cells do not express NeuGc, and an Epstein-Barr virus-transformed
      human B lymphocyte line analyzed in this study retained this sialylation status,
      expressing exclusively GM3 (NeuAc) (100%). The fusion of human B lymphocytes with
      mouse myelomas led to high GM3 (NeuGc) expression (average about 85%) in all
      mouse/human heterohybridomas examined. Our results indicate the chromosomal gene
      "transfer" and/or the activation of enzymes involved in NeuGc-biosynthesis due to
      the somatic cell fusion process, which might explain the mouse dominance in the
      manifestation of the NeuGc-phenotype in hybridomas of human origin.

PMID- 7528203
TI  - A major glucocorticoid-inducible P450 in rat liver is not P450 3A1.
AB  - A new P450 3A cDNA (RL33) has been cloned from a liver cDNA library of untreated
      male rat. RL33 is 2032 nucleotides in length and has an open reading frame of 502
      amino acid residues. The nucleotide sequence of its 5'-noncoding region is
      completely identical with that of a genomic clone of P450 3A1 isolated by Burger
      et al. [Proc. Natl. Acad. Sci. USA 89, 2145-2149 (1992)]. Compared with rat P450
      3A1, P450 RL33 showed 98 and 97% identities in the nucleotide and deduced amino
      acid sequences, respectively, with the deletion of 2 amino acids and substitution
      of 12 amino acids. These residues were localized around amino acids 107-230.
      Recently Kirita and Matsubara have isolated the same P450 3A cDNA (cDEX) from
      dexamethasone (DEX)-treated rat liver [Arch. Biochem. Biophys. 307, 253-258
      (1993)]. Northern blot analysis using an oligonucleotide probe specific for P450
      RL33/cDEX revealed that P450 RL33/cDEX mRNA was induced strongly by pregnenolone
      16 alpha-carbonitrile and DEX and weakly by phenobarbital (PB) and
      triacetyloleandomycin. We constructed a P450 3A cDNA library by the reverse
      transcriptase-polymerase chain reaction using common primers to P450 RL33/cDEX,
      3A1, and 3A2, and subcloned the cDNAs into pUC119. The expression level of P450
      RL33/cDEX mRNA was investigated by identifying each clone with the above
      oligonucleotide probe. P450 RL33/cDEX mRNA represented over 70% of the total P450
      3A mRNA from untreated, PB-, and DEX-treated rat liver. These results indicated
      that the major DEX-inducible form of P450 3A is P450 RL33/cDEX and not P450 3A1.

PMID- 7528205
TI  - Interaction between FKBP12-rapamycin and TOR involves a conserved serine residue.
AB  - The yeast TOR1 and TOR2 proteins were previously discovered as putative targets
      of the immunosuppressive drug rapamycin. Although their cellular function is
      unknown, they are predicted to be at least 215 kDa in size and possess a C
      terminal phosphatidylinositol (PI) kinase-related domain. We previously
      identified a conserved Ser residue, within the PI kinase-related domain of both
      yeast TOR proteins (Ser1972 in TOR1; Ser1975 in TOR2), as being the site of
      missense mutations conferring dominant rapamycin resistance. The Ser1972/1975
      residue of yeast TOR is conserved in mammalian TOR homologs. One possibility is
      that this residue is critical for a direct interaction between TOR and the FKBP12
      rapamycin complex. There is very recent biochemical evidence for an interaction
      between mammalian TOR and FKBP12-rapamycin (Brown, E. J., Albers, M. W., Shin, T.
      B., Ichikawa, K., Keith, C. T., Lane, W. S., and Schreiber, S. L. (1994) Nature
      369, 756-758; Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., and
      Snyder, S. H. (1994) Cell 78, 35-43). Using the yeast two-hybrid system, we now
      have obtained genetic proof of a physical interaction between FKBP12-rapamycin
      and TOR and have demonstrated that this interaction requires the conserved Ser
      residue. We have found that a small fragment of wild-type yeast TOR2 spanning
      Ser1975 is capable of interacting with human FKBP12 in the presence of rapamycin,
      whereas an Arg1975 mutant fails to interact. This effect is dependent upon
      rapamycin and is antagonized by FK506.

PMID- 7528206
TI  - Calmodulin controls neuronal nitric-oxide synthase by a dual mechanism.
      Activation of intra- and interdomain electron transfer.
AB  - In neuronal nitric-oxide synthase (NOS), electron transfer proceeds across
      domains in a linear sequence from NADPH to flavins to heme, with calmodulin (CaM)
      triggering the interdomain electron transfer to the heme (Abu-Soud, H. M., and
      Stuehr, D. J. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10769-10772). Here, we
      utilized a neuronal NOS devoid of its bound heme and tetrahydrobiopterin (apo
      NOS) to examine whether interdomain electron transfer is responsible for CaM's
      activation of NO synthesis, substrate-independent NADPH oxidation, and cytochrome
      c and ferricyanide reduction. Of the four activities, two (cytochrome c and
      ferricyanide reduction) were similarly stimulated by CaM in apo-NOS when compared
      with native NOS, indicating that activation occurs by a mechanism not involving
      flavin-to-heme electron transfer. Further analysis showed that CaM increased the
      rate of electron transfer from NADPH into the flavin centers by a factor of 20,
      revealing a direct activation of the NOS reductase domain by CaM. In contrast,
      CaM's activation of NO synthesis and substrate-independent NADPH oxidation
      appeared to involve flavin-to-heme electron transfer because these reactions were
      not activated in apo-NOS and were blocked in native NOS by agents that prevent
      heme iron reduction. Thus, CaM activates neuronal NOS at two points in the
      electron transfer sequence: electron transfer into the flavins and interdomain
      electron transfer between the flavins and heme. Activation at each point is
      associated with an up-regulation of domain-specific catalytic functions. The dual
      regulation by CaM is unique and represents a new means by which electron transfer
      can be controlled in a metalloflavoprotein.

PMID- 7528207
TI  - Isozyme-specific inhibition of protein kinase C by RNA aptamers.
AB  - In vitro selection technology has been used to purify RNA aptamers from a random
      sequence pool that can bind to, and specifically inhibit, protein kinase C beta
      II. Two of the selected RNA aptamers bind to this isozyme of protein kinase C
      with nanomolar affinities and inhibit activation with unprecedented selectivity;
      the highly related, alternatively spliced beta I isozyme, which differs by 23
      residues, is inhibited with 1 order of magnitude lower potency; the next most
      similar isozyme, alpha, shows no detectable inhibition. The production of isozyme
      specific inhibitors of protein kinase C opens the possibilities for dissecting
      the roles of specific protein kinase Cs in the myriad of intracellular signalling
      pathways.

PMID- 7528208
TI  - Induction of chemokine gene expression by major histocompatibility complex class
      II ligands in human fibroblast-like synoviocytes. Differential regulation by
      interleukin-4 and dexamethasone.
AB  - Chemokines play a key role in recruiting leukocytes into inflamed synovial
      environment, and the cells of the synovial membrane, which express high levels of
      major histocompatibility complex (MHC) class II molecules, are a major source of
      these chemokines. Our data indicated that engagement of MHC class II molecules by
      staphylococcal enterotoxin A superantigen resulted in the induction of chemokine
      gene expression as well as protein synthesis. Pretreatment of the cells with
      cycloheximide potentiated the effect of superantigen on chemokine mRNA induction,
      suggesting that the expression of these genes may occur independently of prior
      protein synthesis. Ligation of MHC class II molecules in fibroblast-like
      synoviocytes by other ligands such as Mycoplasma arthritidis-derived superantigen
      and anti-class II antibody could also trigger an increase in the mRNA level of
      RANTES, MCP-1, and interleukin (IL)-8. The addition of dexamethasone to
      superantigen-treated fibroblast-like synoviocytes inhibited the mRNA expression
      of all three chemokines. IL-4 treatment decreased only the stimulating effect of
      superantigen on RANTES messanger suggesting that different mechanisms are
      involved in regulating these genes. The inhibitory effect of dexamethasone did
      not require a de novo protein synthesis, whereas that of IL-4 was protein
      dependent. This report demonstrates that MHC class II ligands (superantigens and
      anti-MHC class II antibodies) may represent an important agent by which
      inflammatory chemokines can be induced and shows that this response can be
      modulated by the anti-inflammatory agents dexamethasone and IL-4.

PMID- 7528209
TI  - A UGU sequence in the anticodon loop is a minimum requirement for recognition by
      Escherichia coli tRNA-guanine transglycosylase.
AB  - Escherichia coli tRNA-guanine transglycosylase is an enzyme which catalyzes
      replacement of guanine (G34) of tRNA(Asp), tRNA(Asn), tRNA(His) and tRNA(Tyr) by
      free guanine or free preQ1 base by a base exchange reaction in the biosynthesis
      of queuosine (Q) (Okada, N., and Nishimura, S. (1979) J. Biol. Chem. 254, 3061
      3066). The gene encoding for this enzyme was amplified from the E. coli genome by
      polymerase chain reaction and inserted into an overexpression vector, pJLA503.
      The enzyme was overexpressed by heat induction in E. coli transformed by this
      recombinant plasmid and purified to homogeneity by two column chromatographies.
      The sequence requirement in tRNA for recognition by this enzyme was investigated
      using minihelices corresponding to the anti-codon arm of E. coli tRNA(His). Two
      uridine residues (U33, U35) were found to be prerequisite for such recognition by
      this enzyme. Position 32 required pyrimidines, because the enzyme activity toward
      the minihelices was markedly reduced or entirely lost when this residue was
      replaced by purines or was deleted. Adenosine at position 37 and the G30-C40 base
      pair were not essential despite their conservation. Our results suggest that the
      enzyme recognizes the U33-G34-U35 sequence in the anti-codon loop and not the
      tertiary structure of tRNA itself.

PMID- 7528210
TI  - Differential effects of monoclonal antibodies on activating transcription factor
      1 and cAMP response element binding protein interactions with DNA.
AB  - Activating transcription factor-1 (ATF1) and cAMP response element binding
      protein (CREB) have been implicated in cAMP-, calcium-, and virus-induced
      transcriptional alterations. Although CREB and ATF1 share extensive homology,
      they appear to mediate distinct cellular functions. We investigated the effect on
      DNA binding and in vitro transcription of four monoclonal antibodies (mAb) that
      bound to domains in either the regulatory region (mAb 1 and 3) or unique regions
      near the DNA-binding domains (mAb 4 and 5) of ATF1.mAb 1 and 3 supershifted both
      ATF1 and CREB in a DNA binding assay but did not affect in vitro transcription.
      mAb 4 prevented ATF1-DNA binding while supershifting CREB.DNA complexes and
      inhibited in vitro transcription by 95% from the CRE-containing murine
      proliferating cell nuclear antigen promoter. mAb 5 reacted specifically with ATF1
      and did not prevent DNA binding or affect in vitro transcription. The mAb 4
      epitope was located within ATF1 amino acid residues 205-219, including the first
      3 basic residues in the putative DNA-binding domain. Secondary structural
      analysis predicted that this region comprises a transition site from alpha-helix
      to a turn-like conformation in ATF1. The transition to turn-like motifs is
      predicted to occur in CREB after 5 additional residues, with a correspondingly
      longer alpha-helical domain. Although regulatory domains distinct from DNA
      binding regions are thought to account for most of the differences in activity of
      members of the CREB subfamily, our results suggest that small structural
      variations adjacent to DNA binding regions may also contribute to the distinct
      functional activities of ATF1 and CREB.

PMID- 7528211
TI  - Differential effect of cell-associated heparan sulfates on the binding of
      keratinocyte growth factor (KGF) and acidic fibroblast growth factor to the KGF
      receptor.
AB  - The fibroblast growth factors (FGFs) act through high affinity tyrosine kinase
      receptors and, in addition, interact with lower affinity receptors that represent
      cell- or matrix-associated heparan sulfate proteoglycans. These lower affinity
      receptors modulate the biological activities of FGFs, but the mechanism by which
      they exert these effects is rather controversial. We have previously shown (Ron,
      D., Bottaro, D. P., Finch, P. W., Morris, D., Rubin, J. S., and Aaronson, S. A.
      (1993) J. Biol. Chem. 268, 2984-2988) that heparin potentiates the mitogenic
      activity of acidic FGF (aFGF) but inhibits that of the keratinocyte growth factor
      (KGF) in cells that express the KGF receptor (KGFR). Both growth factors bind the
      KGFR with high affinity. To gain an insight into the mechanism by which heparin
      modulates the biological activity of aFGF and KGF, we studied the effect of
      heparin and cell-associated heparan sulfates on the binding of these two growth
      factors to the KGFR. To work in a well defined system, we expressed functional
      KGFR in L6E9 myoblasts that lack detectable high affinity binding sites for FGFs.
      Low concentrations of heparin inhibited the binding of KGF to the KGFR. By
      contrast, similar concentrations of heparin enhanced the binding of aFGF to this
      receptor. The effect of heparin was not unique to L6E9 cells expressing the KGFR;
      it was also observed in Balb/MK cells that naturally express KGFR. Treatment of
      cells with sodium chlorate, which blocks sulfation of proteoglycans, reduced the
      binding of aFGF to its low and high affinity binding sites by 95 and 80%,
      respectively. In contrast, the binding of KGF to its high affinity binding sites
      was enhanced about 2-fold. Similar results were obtained after degradation of
      cell-associated heparan sulfates by heparinase and heparitinase. Heparin restored
      the high affinity binding of aFGF to chlorate-treated cells and completely
      abolished the high affinity binding of KGF. Binding competition experiments
      suggest that aFGF and KGF bind to the same population of cell-associated heparan
      sulfates. In addition, KGF is apparently interacting with an as yet unidentified
      type of low affinity binding site that is not affected by chlorate or heparan
      sulfate-degrading enzymes. An important property of the FGF high affinity
      receptors is their ability to bind more than one ligand with high affinity. Based
      on the differential effect of cell-associated heparan sulfates on the binding of
      KGF and aFGF to the KGFR, we propose a regulatory role for cell-associated
      heparan sulfates as coordinators of the interaction of aFGF and KGF with the
      KGFR.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7528212
TI  - Electron transfer in the nitric-oxide synthases. Characterization of L-arginine
      analogs that block heme iron reduction.
AB  - Heme iron reduction in the nitric-oxide synthases (NOSs) requires calmodulin
      binding and is associated with increased NO synthesis and NADPH oxidation (Abu
      Soud, H. M., and Stuehr, D. J. (1993) Proc. Natl. Acad. Sci., U. S. A. 90, 10769
      10772). Here, we examined how L-arginine and the analogs N omega-methyl-L
      arginine (NMA), N omega-nitro-L-arginine methyl ester (NAME), and d-(thioureido)
      L-norvaline (thiocitrulline) affect electron flux through neuronal and macrophage
      NOS. L-Arginine and NMA increased or decreased NOS NADPH consumption depending on
      the isoform, while thiocitrulline and NAME decreased NADPH oxidation in both NOS
      by 73-86% relative to their ligand-free rates. Kinetic studies showed that
      thiocitrulline and NAME inhibited NOS NADPH consumption through binding within
      the substrate binding site. Thiocitrulline and NAME did not affect the NADPH
      dependent reduction of NOS flavins nor NOS cytochrome c reduction, indicating
      that they blocked electron flux at a point beyond the flavins in the electron
      transfer sequence. Thiocitrulline and NAME inhibited both NADPH-dependent and
      dithionite-mediated heme iron reduction in the NOS isoforms relative to the
      substrate-free NOS, whereas L-arginine and NMA did not. Thus, L-arginine and NMA
      increase or decrease electron flux through the NOS by coupling NADPH oxidation to
      NO synthesis (L-arginine), or by occupying the substrate binding site with
      minimal catalytic coupling (NMA). In contrast, thiocitrulline and NAME decrease
      electron flux through both NOS isoforms by decreasing the reduction potential of
      the heme iron. Inhibition of heme iron reduction by substrate analogs is unusual
      and represents a new means to modulate electron flow through the NOS.

PMID- 7528213
TI  - Expression of distinct fucosylated oligosaccharides and carbohydrate-mediated
      adhesion efficiency directed by two different alpha-1,3-fucosyltransferases.
      Comparison of E- and L-selectin-mediated adhesion.
AB  - Among five different human alpha 1 --> 3 fucosyltransferases cloned,
      fucosyltransferases III (Fuc-TIII) and IV (Fuc-TIV) differ significantly from
      each other. Fuc-TIII transfers a fucose to both sialylated and nonsialylated N
      acetyllactosamine, but Fuc-TIV apparently transfers a fucose only to neutral N
      acetyllactosamine. In this study, Chinese hamster ovary (CHO) cells were stably
      transfected with Fuc-TIII or Fuc-TIV, and the resultant cell lines, CHO-FTIII and
      CHO-FTIV, were compared for the carbohydrate structures and for their binding to
      E-selectin or L-selectin. CHO-FTIII and CHO-FTIV cells were labeled metabolically
      with [3H]galactose, and glycopeptides obtained from these cells were fractionated
      by serial lectin affinity chromatography. The fractionated glycopeptides were
      then subjected to various combinations of exoglycosidase treatment or endo-beta
      galactosidase digestion. The results obtained can be summarized as follows. CHO
      FTIII cells express sialyl Lewisx, Lewisx, and VIM-2 structures, whereas CHO-FTIV
      cells express only an Lex structure with a small amount of VIM-2 structure. When
      CHO-FTIII and CHO-FTIV cells were tested for adhesion to E-selectin expressed by
      tumor necrosis factor-activated endothelial cells and to an E-selectin chimeric
      protein, only CHO-FTIII cells were found to adhere well to E-selectin. Moreover,
      both CHO-FTIII and CHO-FTIV cells failed to adhere to an L-selectin chimeric
      protein. These results clearly indicate that FT-III and FT-IV direct distinctly
      different fucosylated oligosaccharides. This difference in oligosaccharide
      structures results in an entirely different efficiency in adhesion to E-selectin.
      The results also demonstrate that expression of sialyl Lex itself is not
      sufficient for L-selectin binding.

PMID- 7528214
TI  - Inhibition of HIV-1 reverse transcriptase by a quinazolinone and comparison with
      inhibition by pyridinones. Differences in the rates of inhibitor binding and in
      synergistic inhibition with nucleoside analogs.
AB  - 6-Chloro-(4S)-cyclopropyl-3,4-dihydro-4-((2-pyridyl)-ethynyl)quinazol in- 2(1H)
      one (L-738,372) is representative of a novel structural class of nonnucleoside
      inhibitors of human immunodeficiency virus, strain 1 (HIV-1), reverse
      transcriptase (RT), the quinazolinones. L-738,372 is a reversible inhibitor of
      HIV-1 RT and is noncompetitive against dTTP with a Ki of 140 nM with
      poly(rA).oligo(dT) as primer-template. Mixed noncompetitive inhibition by L
      738,372 was observed against poly(rC).oligo(dG) as primer-template. This
      quinazolinone binds to RT at a site that overlaps the binding site of other
      nonnucleoside inhibitors as evidenced by the ability of L-738,372 to displace
      bound radiolabeled L-696,229, a member of the pyridinone class of inhibitors of
      HIV-1 RT, from complexes of RT and primer-template. Inhibition by L-738,372 shows
      slow binding characteristics in reactions with all of the primer-templates
      employed. Synergistic inhibition of RT activity was evident in combinations of L
      738,372 and any of the nucleoside analogs, azidothymidine triphosphate,
      dideoxyinosine triphosphate, or dideoxycytosine triphosphate. The azidothymidine
      resistant form of RT (D67N, K70R, T215Y, K219Q) is inhibited by L-738,372 with 2
      3-fold more potency than is the wild-type RT. Comparison of inhibition by L
      738,372 with inhibition by pyridinone inhibitors reveals differences in
      synergistic inhibition with nucleoside analogs and in the rates of binding of the
      inhibitors.

PMID- 7528215
TI  - Identification of the urokinase receptor as an adhesion receptor for vitronectin.
AB  - Urokinase receptors, expressed on surfaces of many cell types, focus to the
      pericellular space plasminogen-dependent proteolysis important in matrix
      remodeling and cell movement. We now report that the urokinase receptor (uPAR) is
      also a high affinity (Kd < 30 nM) receptor for vitronectin. Recombinant uPAR
      binds vitronectin in the absence of urokinase, but vitronectin binding is
      promoted by concurrent receptor binding of either urokinase or fragments thereof
      containing its uPAR binding domain. Stable epithelial cell transfectants
      expressing membrane-anchored uPAR, but not cells expressing soluble uPAR, become
      strongly adhesive with altered morphology in the absence of urokinase. These
      observations identify a new class of vitronectin receptor and imply a duality in
      function for the receptor that intrinsically links matrix adhesion to regulation
      of protease activity. Increases in urokinase receptor expression known to be
      associated with cellular activation and malignant transformation could modulate
      cellular trafficking and function by promoting attachment to vitronectin.

PMID- 7528217
TI  - The HLA-B14 peptide binding site can accommodate peptides with different
      combinations of anchor residues.
AB  - Most peptides that bind to a particular major histocompatibility complex class I
      molecule share amino acid residues important for binding at one or two positions.
      Sequence analyses of peptides bound to HLA-B14 revealed at least four candidates
      for these so-called anchor residues: Arg at P2, Tyr at P3, Arg at P5, and Leu at
      P9. Combinations of any three of these amino acids sufficed for binding to HLA
      B14 in vitro. Using this information, we identified an antigenic peptide critical
      for cytotoxic T lymphocyte recognition of virus-infected cells. Molecular models
      of HLA-B14 peptide complexes were constructed to investigate how the potential
      anchor residues might function. By using binding data to calculate the
      contribution to binding of each amino acid at anchor positions and predicting the
      stability of all possible nonapeptide complexes that could be formed from
      antigenic proteins, we estimate that three known antigenic nonapeptides are in
      the highest affinity cohort of peptides. Thus, even when multiple combinations of
      anchor residues contribute to binding, antigenic peptides are routinely
      identifiable.

PMID- 7528218
TI  - Signaling through CD19 activates Vav/mitogen-activated protein kinase pathway and
      induces formation of a CD19/Vav/phosphatidylinositol 3-kinase complex in human B
      cell precursors.
AB  - The B cell-specific cell surface molecule CD19 plays a role in regulating
      immunoglobulin (Ig) receptor signaling, and cross-linking CD19 activates several
      signaling molecules in mature human B cells. In surface Ig-negative B cell
      precursors, a protein tyrosine kinase (PTK)-dependent homotypic aggregation
      response can be triggered by cross-linking CD19. In the current study, we
      examined the outcome of PTK-mediated signal transduction following CD19 cross
      linking on surface Ig negative and surface Ig positive B cell lines, as well as
      freshly isolated surface Ig-negative B cell precursors. PTK activation resulted
      in the tyrosine phosphorylation of multiple protein substrates and peaked at 0.5
      1 min following CD19 cross-linking in all B-lineage cells examined. One of the
      tyrosine-phosphorylated substrates was identified as the hematopoietic-specific
      protein Vav, a guanine nucleotide exchange factor that activates the Ras pathway.
      Evidence consistent with Ras pathway activation was also demonstrated by MEK
      activation and subsequent phosphorylation of a MAP kinase fusion protein. CD19
      cross-linking, sequential immunoprecipitation, and Western blotting revealed
      that: (a) Vav becomes associated with CD19, (b) phosphatidylinositol 3-kinase (PI
      3-kinase) becomes associated with CD19, and (c) PI 3-kinase becomes associated
      with Vav. No such physical interaction occurred following control IgG1 cross
      linking or cross-linking of class I major histocompatability complex cell surface
      molecules. Coupled with a previous report (Tuveson, D.A., Carter, R.H., Soltoff,
      S.P., and Fearon, D.T. (1993) Science 260, 986-988), our data support a model in
      which CD19 cross-linking induces the formation of a signaling complex that leads
      to the activation of two pathways involving Ras and PI 3-kinase.

PMID- 7528216
TI  - Ganglioside GD1 alpha in cerebellar Purkinje cells. Its specific absence in mouse
      mutants with Purkinje cell abnormality and altered immunoreactivity in response
      to conjunctive stimuli causing long-term desensitization.
AB  - The alpha-series ganglioside, IV3NeuAc,III6NeuAcGgOse4-Cer(GD1 alpha), was
      previously identified as a minor constituent in bovine brain gangliosides
      (Hirabayashi, Y., Hyogo, A., Nakao, T., Tsuchiya, K., Suzuki, Y., Matsumoto, M.,
      Kon, K, and Ando, S. (1990) J. Biol. Chem. 265, 8144-8151). In the present study,
      we have generated a specific mouse monoclonal antibody against GD1 alpha and
      explored the distribution of GD1 alpha in murine central nervous system. In adult
      rat brain, GD1 alpha occurred as a minor constituent, and its expression was
      exclusively detected in the forebrain, the midbrain and the cerebellum. In the
      mouse cerebellum, the content of GD1 alpha was reduced significantly in the
      Purkinje cell-deficient mutants, lurcher (Lc/+), staggerer (sg/sg), and Purkinje
      cell degeneration (pcd/pcd), but were not reduced in the weaver (wv/wv) mutant,
      which loses mostly granule cells. The GD1 alpha synthase, assayed in cerebellar
      microsomes, was also reduced in Purkinje cell-deficient mutants.
      Immunohistochemistry showed that the staining for GD1 alpha in rat and mouse
      cerebella was mostly found in the proximal dendrites and cell bodies of Purkinje
      cells. Also, it appeared slightly in the processes of Bergmann glial cells. The
      immunoreactivity of GD1 alpha disappeared specifically from the Purkinje cell
      dendrites and the Bergmann glial processes after co-application of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and 8-bromo-guanosine 3':5'
      cyclic monophosphate, which induced long-term desensitization of the AMPA
      selective glutamate receptors in Purkinje cells. The present data provide
      suggestive evidence that GD1 alpha ganglioside is enriched in Purkinje cells and
      may have a role in Purkinje cell functions in the cerebellum.

PMID- 7528219
TI  - Regulation of macrophage receptor-bound plasmin by autoproteolysis.
AB  - The activation of plasminogen by macrophage is regulated by their expression of
      receptors for urokinase and plasmin(ogen). In these studies we have examined
      plasmin(ogen) binding to adherent human THP-1 macrophage. Plasmin bound to the
      THP-1 cells in a time- and dose-dependent manner (Kd 15.8 +/- 6.2 nM; Bmax 1.4 +/
      0.3 x 10(6)/cell). The lysine analog epsilon-aminocaproic acid competitively
      inhibited plasmin binding. The fraction of membrane-bound plasmin, however,
      became increasingly resistant to displacement with epsilon-aminocaproic acid.
      Over a 24-h period, membrane-bound plasmin activity fell 80% despite the presence
      of catalytically active plasmin in the incubation media. The loss of receptor
      bound plasmin activity was not due to proteolytic alterations of its receptor
      since 125I-Lys-plasminogen bound to THP-1 cells pretreated with plasmin with
      similar affinity as to untreated cells. Following a 24-h incubation of 125I-Lys
      plasminogen or 125I-plasmin with THP-1 cells, several degradative fragments were
      apparent in their conditioned media. The smaller degradative fragments (28 and 36
      kDa) lacked cell binding activity and were demonstrated to be active by casein
      zymography. A 48-kDa fragment bound to cells in a lysine-dependent manner but was
      not active. In contrast, phenylmethylsulfonyl fluoride-inactivated 125I-plasmin
      retained its binding activity over 24 h, and degradative fragments were not
      present in the conditioned media. The binding of 125I-Lys-plasmin(ogen) to THP-1
      cells was also examined in the presence of excess alpha 2 plasmin inhibitor.
      Despite the absence of fluid-phase plasmin activity, membrane-bound 125I-Lys
      plasmin(ogen) decreased over 24 h. At 24 h a radiolabeled 48-kDa fragment was
      observed in the conditioned media and together with 125I-Lys-plasmin(ogen) was
      bound to cells. Unlike 125I-Lys-plasmin, the 48-kDa fragment did not form a
      complex with alpha 2 plasmin inhibitor. Thus, autoproteolysis of receptor-bound
      plasmin results in fragments with truncated physiologic properties that possess
      either cell binding or catalytic activities. We propose that autoproteolysis is a
      mechanism for regulating membrane-bound plasmin activity.

PMID- 7528220
TI  - Differential phosphorylation in vivo of cytoplasmic dynein associated with
      anterogradely moving organelles.
AB  - Two microtubule-stimulated ATPases, cytoplasmic dynein, and kinesin, are believed
      to be responsible for the intracellular movement of membrane-bound organelles in
      opposite directions along microtubules. An unresolved component of this model is
      the mechanism by which cells regulate these two motors to direct various membrane
      bound organelles to their proper locations. To determine if phosphorylation may
      play a role in the regulation of cytoplasmic dynein, the in vivo phosphorylation
      state of cytoplasmic dynein from two cellular pools was examined. The entire
      cellular pool of brain cytoplasmic dynein was metabolically labeled by the
      infusion of [32P]orthophosphate into the cerebrospinal fluid of rat brain
      ventricles. To characterize the phosphorylation of dynein associated with
      anterograde membrane-bound organelles, the optic nerve fast axonal transport
      system was used. Using a monoclonal antibody to the 74-kD polypeptide of brain
      cytoplasmic dynein, the native dynein complex was immunoprecipitated from the
      radiolabled tissue extracts. Autoradiographs of one and two dimensional gels
      showed labeling of nearly all of the polypeptide isoforms of cytoplasmic dynein
      from rat brain. These polypeptides are phosphorylated on serine residues.
      Comparison of the amount of 32P incorporated into the dynein polypeptides
      revealed differences in the phosphorylation of dynein polypeptides from the
      anterograde and the cellular pools. Most interestingly, the 530-kD heavy chain of
      dynein appears to be phosphorylated to a lesser extent in the anterograde pool
      than in the cellular pool. Since the anterograde pool contains inactive dynein,
      while the entire cellular pool contains both inactive and active dynein, these
      results are consistent with the hypothesis that phosphorylation regulates the
      functional activity of cytoplasmic dynein.

PMID- 7528221
TI  - Interactions of the chondroitin sulfate proteoglycan phosphacan, the
      extracellular domain of a receptor-type protein tyrosine phosphatase, with
      neurons, glia, and neural cell adhesion molecules.
AB  - Phosphacan is a chondroitin sulfate proteoglycan produced by glial cells in the
      central nervous system, and represents the extracellular domain of a receptor
      type protein tyrosine phosphatase (RPTP zeta/beta). We previously demonstrated
      that soluble phosphacan inhibited the aggregation of microbeads coated with N-CAM
      or Ng-CAM, and have now found that soluble 125I-phosphacan bound reversibly to
      these neural cell adhesion molecules, but not to a number of other cell surface
      and extracellular matrix proteins. The binding was saturable, and Scatchard plots
      indicated a single high affinity binding site with a Kd of approximately 0.1 nM.
      Binding was reduced by approximately 15% after chondroitinase treatment, and free
      chondroitin sulfate was only moderately inhibitory, indicating that the
      phosphacan core glycoprotein accounts for most of the binding activity.
      Immunocytochemical studies of embryonic rat spinal phosphacan, Ng-CAM, and N-CAM
      have overlapping distributions. When dissociated neurons were incubated on dishes
      coated with combinations of phosphacan and Ng-CAM, neuronal adhesion and neurite
      growth were inhibited. 125I-phosphacan bound to neurons, and the binding was
      inhibited by antibodies against Ng-CAM and N-CAM, suggesting that these CAMs are
      major receptors for phosphacan on neurons. C6 glioma cells, which express
      phosphacan, adhered to dishes coated with Ng-CAM, and low concentrations of
      phosphacan inhibited adhesion to Ng-CAM but not to laminin and fibronectin. Our
      studies suggest that by binding to neural cell adhesion molecules, and possibly
      also by competing for ligands of the transmembrane phosphatase, phosphacan may
      play a major role in modulating neuronal and glial adhesion, neurite growth, and
      signal transduction during the development of the central nervous system.

PMID- 7528222
TI  - Hepatocyte growth factor induces proliferation and differentiation of multipotent
      and erythroid hemopoietic progenitors.
AB  - Hepatocyte growth factor (HGF) is a mesenchymal derived growth factor known to
      induce proliferation and "scattering" of epithelial and endothelial cells. Its
      receptor is the tyrosine kinase encoded by the c-MET protooncogene. Here we show
      that highly purified recombinant HGF stimulates hemopoietic progenitors to form
      colonies in vitro. In the presence of erythropoietin, picomolar concentrations of
      HGF induced the formation of erythroid burst-forming unit colonies from CD34
      positive cells purified from human bone marrow, peripheral blood, or umbilical
      cord blood. The growth stimulatory activity was restricted to the erythroid
      lineage. HGF also stimulated the formation of multipotent CFU-GEMM colonies. This
      effect is synergized by stem cell factor, the ligand of the tyrosine kinase
      receptor encoded by the c-KIT protooncogene, which is active on early hemopoietic
      progenitors. By flow cytometry analysis, the receptor for HGF was found to be
      expressed on the cell surface in a fraction of CD34+ progenitors. Moreover, in
      situ hybridization experiments showed that HGF receptor mRNA is highly expressed
      in embryonic erythroid cells (megaloblasts). HGF mRNA was also found to be
      produced in the embryonal liver. These data show that HGF plays a direct role in
      the control of proliferation and differentiation of erythroid progenitors, and
      they suggest that it may be one of the long-sought mediators of paracrine
      interactions between stromal and hemopoietic cells within the hemopoietic
      microenvironment.

PMID- 7528223
TI  - Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in
      photochemically induced ischemia of the rat cortex.
AB  - The contribution of the immune system to the pathogenesis of ischemic lesions is
      still uncertain. We have analyzed leukocyte infiltration in photochemically
      induced focal ischemia of the rat parietal cortex by immunocytochemistry. Between
      1 and 2 days after photothrombosis, CD5+ T cells adhered to subpial and cortical
      vessels and infiltrated the ischemic lesion prior to macrophages. By day 3
      numerous T cells and some macrophages, whose number increased further between day
      3 and day 7, had infiltrated the border zone around the lesion sparing the
      center. In addition, CD5-/CD8+ lymphocytes that probably represent natural killer
      cells were found. Intercellular adhesion molecule-1 (ICAM-1) was expressed on
      endothelial cells on days 1 and 2 and in the border zone on infiltrating
      leukocytes from day 3 to day 7. Starting on day 7, macrophages infiltrated the
      core of the lesion to remove debris. When the entire lesion was covered by
      macrophages at day 14, the number of T cells had decreased and ICAM-1
      immunoreactivity was no longer found in or around the infarct. In conclusion, our
      study shows that ischemic lesions can lead to a local immune reaction in the CNS.
      Thus, blocking of lymphocyte-derived cytokines or cell adhesion molecules may
      provide a new approach to confining the sequelae of stroke.

PMID- 7528228
TI  - Morphological study of the rostral interstitial nucleus of the medial
      longitudinal fasciculus in the monkey, Macaca mulatta, by Nissl, Golgi, and
      computer reconstruction and rotation methods.
AB  - We have studied the morphology of silver-impregnated neurons (rapid Golgi
      technique) in the rostral interstitial nucleus of the medial longitudinal
      fasciculus (riMLF), a center involved in the control of vertical and torsional
      saccadic eye movements. This morphological study of riMLF neurons in the rhesus
      monkey was undertaken to further our understanding of the functional circuitry of
      the oculomotor system. Our study employed Nissl, Golgi, and computer-assisted
      methods. The cytoarchitectonic boundaries of the riMLF and its relationships to
      neighboring structures were determined in both Nissl and Golgi preparations. Five
      (I-V) distinct morphological types of riMLF neurons were distinguished in the
      Golgi impregnations on the basis of soma size, dendritic size, numbers of primary
      dendrites, number of dendritic branch points, as well as form, number, and
      distribution of dendritic appendages. Type I neurons impregnated most frequently
      and had the most extensive and highly branched dendritic tree. Type II neurons
      displayed thick dendrites with complex dendritic appendages, but the dendritic
      tree was much more compact than that of type I cells. Type III and type V cells
      had fusiform somas and relatively unbranched dendritic trees but differed greatly
      in size as well as dendritic morphology. The type IV cell was the smallest neuron
      and had many characteristics of the local interneurons found in other thalamic,
      subthalamic, hypothalamic and midbrain centers. The type V was the largest
      neuron, least frequently impregnated, and found only at rostral riMLF levels.
      Digitized reconstructions of each type of neuron were rotated by the computer,
      which revealed that the dendritic trees of types I, III, and V occupy a disk-like
      compartment in the riMLF neuropil. In contrast, the tree of types II and IV
      occupy a roughly spherical compartment. We suggest that three of the cell types
      are well suited for specific purposes: type II cells for receiving
      topographically organized inputs that contain spatial information, type I cells
      for short-lead burst neuron output to the motor neurons or other premotor
      centers, and type IV cells for inhibitory inputs to type I cells.

PMID- 7528226
TI  - Seek and ye shall find: research and the primary care pediatrician.

PMID- 7528225
TI  - No evidence of developmental III effects of low-level lead exposure in a
      developing country.
AB  - Despite substantial controversy regarding the blood levels at which lead
      adversely affects neurobehavioral development, public health policy in some
      industrialized countries is prescribing ever more stringent screening criteria
      for all ages. This study addressed the question of ill effects of lead exposure
      at the new lower levels, specifically during the late infancy period, which has
      been targeted for maximum surveillance in pediatric practice. The sample of 184
      participants consisted of 12- to 23-month-old healthy infants and toddlers who
      participated in a community-based study in a developing Central American country
      (Costa Rica) where extensive family and developmental information was collected.
      The mean infant blood lead level was 11.0 micrograms/dL, ranging from 5.4 to 37.0
      micrograms/dL. Lead levels were not related to the Mental or Psychomotor
      Developmental Index of the Bayley Scales of Infant Development. When the children
      were 5 years old, they were reevaluated with complete physical and psychological
      testing. Blood lead levels in infancy did not predict any of the developmental
      outcome measures. Thus, among a group of healthy toddlers in a developing
      country, no ill effects on development of low blood lead levels were observed.

PMID- 7528231
TI  - Nasal challenge with allergen upregulates the local expression of vascular
      endothelial adhesion molecules.
AB  - To understand the events involved in selective eosinophil migration into allergic
      inflammatory sites, we studied the expression of vascular endothelial adhesion
      molecules in the nasal mucosa. Ten subjects with asymptomatic seasonal allergic
      rhinitis and 13 nonallergic subjects underwent localized allergen challenge of
      one inferior turbinate. Twenty-four hours later, biopsy specimens were obtained
      from the inferior turbinates, bilaterally in the seasonally allergic subjects and
      unilaterally in the nonallergic control subjects. The specimens were divided,
      sectioned, and either stained for identification of eosinophils or analyzed
      immunohistochemically for intercellular adhesion molecule-1, E-selectin, vascular
      cell adhesion molecule-1 (VCAM-1), and von Willebrand's factor. Intercellular
      adhesion molecule-1 expression was observed in all mucosal specimens, with no
      significant difference among groups. E-selectin showed minimal baseline
      expression, and low levels were significantly induced on the challenged mucosa of
      the allergic compared with nonallergic subjects (p < 0.05). VCAM-1 was expressed
      basally and was significantly upregulated by allergen challenge, compared with
      the nonchallenged side and nonallergic control subjects (p < 0.05). Submucosal
      eosinophils increased significantly in allergic subjects 24 hours after antigen
      challenge, compared with nonallergic control subjects and weakly correlated with
      VCAM-1 expression (rs = 0.33, p = 0.06). Our results suggest that endothelial
      activation accompanies allergic inflammation. Furthermore, because the
      counterligand for VCAM-1, very late activation antigen-4, is present on
      eosinophils, VCAM-1 upregulation may contribute to the selective recruitment of
      these cells to the nasal mucosa.

PMID- 7528227
TI  - Preoptic projections to Barrington's nucleus and the pericoerulear region:
      architecture and terminal organization.
AB  - The medial preoptic area (MPO), a sexually dimorphic region, plays a pivotal role
      in neuroendocrine function and reproductive behavior. We recently reported that
      MPO projects heavily to the midbrain periaqueductal gray (PAG). We also noted
      that MPO projects to the dorsolateral pontine tegmentum. Here we identified the
      cells of origin of the MPO-->tegmental projection and delineated the terminal
      organization of MPO projections to Barrington's nucleus, locus coeruleus (LC),
      and the rostromedial pericoerulear region (pLCrm). Correlative cyto- and
      chemoarchitectonic studies were done to define better the nuclear groups of the
      dorsolateral pontine tegmentum. Retrograde tracing revealed that MPO neurons
      projecting to the dorsolateral pontine tegmentum are preferentially distributed
      in distinct subregions of MPO, including the sexually dimorphic medial preoptic
      nucleus (MPN). Anterograde tracing with wheat germ agglutinin-horseradish
      peroxidase or Phaseolus vulgaris leucoagglutinin demonstrated considerable target
      specificity in projections from MPO to the dorsolateral pontine tegmentum.
      Barrington's nucleus receives a dense focal input along its entire rostrocaudal
      axis. In addition, pLCrm is heavily targeted by MPO inputs; pLCrm contains a
      concentrated plexus of extranuclear dendrites of LC neurons. The lateral dorsal
      tegmental (LDT) nucleus and LC proper receive only sparse input from MPO. MPO
      projections to Barrington's nucleus could regulate micturition reflexes during
      reproductive behavior. The MPO-->pLCrm projection could influence noradrenergic
      LC neurons in relation to reproductive and/or gonadal steroid function. Given the
      strong established connections from olfactory structures to MPO, it is possible
      that the MPO-->LC pathway provides an anatomical substrate for olfactory
      modulation of arousal.

PMID- 7528230
TI  - Clinical and immunohistochemical studies of skin eruptions: relationship to
      administration of interferon-alpha.
AB  - We observed transient, erythematous skin eruptions in 6 patients during the
      intravenous administration of interferon (INF)-alpha for chronic active hepatitis
      C. The eruptions appeared 5 to 14 days (mean: 6.8 days) after initiating its
      administration. They were localized or disseminated and consisted of edematous,
      erythematous, and/or papular changes. Vesicles and petechiae also appeared in
      some cases. The eruptions disappeared in 10 to 14 days, despite the continuance
      of INF-alpha and without specific treatment. Histological examination obtained
      from skin eruptions revealed perivascular infiltration of lymphoid cells, the
      majority which were CD4-positive, of the upper dermis. Edematous changes were
      present in the papillary dermis. Vascular endothelial cells in the upper dermis
      expressed both intercellular adhesion molecule-1 (ICAM-1) and endothelial
      leukocyte adhesion molecule-1 (ELAM-1), while the epidermal keratinocytes
      produced neither. These findings suggested a nonallergic mechanism for such
      eruptions.

PMID- 7528229
TI  - CD34 immunoreactivity distinguishes between scar tissue and residual tumor in re
      excisional specimens of dermatofibrosarcoma protuberans.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor that often
      recurs after simple excision, and therefore usually requires wide surgical re
      excision. It is sometimes difficult to distinguish histologically between
      residual tumor and scar tissue formed in response to the original biopsy. In an
      effort to solve this diagnostic problem, we have examined CD34 immunoreactivity
      in 10 primary biopsies of DFSP, 12 scars, and 7 re-excisional DFSP specimens
      containing residual tumor adjacent to scar tissue. In all 10 primary biopsies of
      DFSP, the tumor cells strongly and uniformly expressed CD34. In the 12 scars,
      only periadnexal cells, endothelial cells, and rare, scattered dendritic cells in
      the dermis were immunolabeled for CD34. In the 7 re-excisions of DFSP, the foci
      of residual DFSP were strongly immunolabeled, while the surrounding scar tissue
      was not. The pattern of CD34 immunoreactivity distinguishes DFSP from scar
      tissue, and thereby may permit more accurate assessment of surgical margins in re
      excisional specimens of DFSP.

PMID- 7528234
TI  - Leukocyte responses to experimental infection with human rhinovirus.

PMID- 7528233
TI  - Eosinophils and basophils in allergic airway inflammation.

PMID- 7528232
TI  - Basophil and eosinophil differentiation in allergic reactions.

PMID- 7528235
TI  - The clinical relevance of basophil releasability.

PMID- 7528236
TI  - Basophils and eosinophils in allergic rhinitis.

PMID- 7528237
TI  - Cytotoxic cells in immunodeficient athymic mice.
AB  - A studies of cytotoxic cells in athymic nude mice demonstrate higher cytotoxic
      activity of NK cells and macrophages than in their euthymic counterparts. The
      higher level of endogenous cytotoxic activity can be considered as complementary
      to the deficiency or lack of thymus dependent T lymphocytes and their functions.
      However, with increased age of mice some T lymphocytes and their functions can be
      demonstrated. By stimulation of splenocytes and lymph node cells in vitro with IL
      2 or anti CD3 antibody cytotoxic activity towards P-815 (NK resistant, LAK
      sensitive) target cells can be generated. There exist data, which indicate that
      the cytotoxic activity is exerted by extrathymic pre-T lymphocytes with TcR gamma
      delta antigenic phenotype. The differences in transplantability of human tumors
      in athymic nude mice cannot be explained by defect in antigen recognition and in
      immune response of athymic nude mice, recipients of the xenografted material. The
      biological relevance in vivo of high endogenous cytotoxicity of NK cells observed
      in many strains of athymic nude mice remains obscure. The availability of new
      immunodeficient mouse models, e.g. scid mice deficient in B and T lymphocytes and
      with low level of NK cells, in which not only xenografted human tumor grow but
      human lymphoid cell can be transplanted as well, opens new and broader
      experimental possibilities, in which new preclinical immunotherapeutical
      approaches can be applied.

PMID- 7528224
TI  - Marked induction of calcium-independent nitric oxide synthase activity after
      focal cerebral ischemia.
AB  - We studied the effect of focal cerebral ischemia on inducible (iNOS) and
      constitutive (cNOS) nitric oxide synthase enzymatic activities in the affected
      brain. The middle cerebral artery (MCA) was occluded in spontaneously
      hypertensive rats. Animals were killed 1, 2, 4, and 7 days later. cNOS and iNOS
      enzymatic activities were determined in the infarcted cortex using the assay of
      Bredt and Snyder. cNOS was assayed in the presence of calcium, whereas iNOS was
      assayed in the absence of calcium and in the presence of tetrahydrobiopterin. The
      validity of the iNOS assay was verified in rats treated with bacterial
      lipopolysaccharide. In these animals, the magnitude of the induction of iNOS
      enzymatic activity in lung, spleen, and brain paralleled the expression of iNOS
      mRNA, assessed by reverse-transcription polymerase chain reaction. After MCA
      occlusion, calcium-dependent (cNOS) activity was markedly reduced only in
      lesioned cerebral cortex at days 1-7 (p < 0.001; analysis of variance and Tukey's
      test). In contrast to cNOS, calcium-independent (iNOS) activity was induced
      substantially in the infarct (p < 0.005) but not in the contralateral intact
      cortex (p > 0.05). iNOS activity peaked at day 2 and was not different from
      baseline at day 7 (p > 0.05). No NADPH diaphorase-positive neurons were observed
      in the area of the lesion at days 1-7. Macrophages appeared at day 2 and invaded
      the infarcted tissue by day 7. At this time, numerous glial fibrillary acidic
      protein-positive astrocytes were observed within the lesion. The results suggest
      that the decline in calcium-dependent (cNOS) activity reflects loss of NOS
      neurons within the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528239
TI  - A mutation in the V1 end domain of keratin 1 in non-epidermolytic palmar-plantar
      keratoderma.
AB  - Mutations in keratin 9 have been found in families with an epidermolytic form of
      palmar-plantar keratoderma (PPK). In another form of PPK (Unna-Thost type),
      epidermolysis is not observed histologically. We studied a pedigree with this non
      epidermolytic form of PPK. By gene linkage analysis, the type I keratin locus
      could be excluded but complete linkage with the type II keratin region was found.
      Sequence analysis identified a single base change in the amino-terminal V1
      variable subdomain of keratin 1, which caused a lysine to isoleucine
      substitution. This non-conservative mutation completely cosegregated with the
      disease and was not observed in 50 unrelated unaffected individuals. An
      examination of keratin amino-terminal sequences revealed a previously unreported
      22-residue window in the V1 subdomain that is conserved among most type II
      keratins. The altered lysine is an invariant residue in this conserved sequence.
      Previously described keratin mutations affect the central regions important for
      filament assembly and stability, and cause diseases characterized by cellular
      degeneration or disruption. This is the first disease mutation in a keratin chain
      variable end region. The observation that it is not associated with epidermolysis
      supports the concept that the amino-terminal domain of keratins may be involved
      in supramolecular interactions of keratin filaments rather than stability.
      Therefore, hyperkeratosis associated with this mutation may be due to
      perturbations in the interactions of the keratin end domain with other cellular
      components.

PMID- 7528241
TI  - Thioredoxin reductase induction coincides with melanin biosynthesis in brown and
      black guinea pigs and in murine melanoma cells.
AB  - X-rays were used to induce melanin biosynthesis in brown and black guinea pigs in
      vivo. During the course of pigmentation, the expression of thioredoxin reductase
      was increased, whereas for the other antioxidant enzymes, superoxide dismutase
      (cytosol Cu/Zn-enzyme), catalase, and glutathione reductase, levels and
      activities decreased. Isobutylmethylxanthine induced eumelanin biosynthesis in
      murine melanoma cells (Cloudman S-91). In these cells, thioredoxin reductase
      levels coincided with melanogenesis. Our results suggest that both tyrosinase and
      thioredoxin reductase respond to oxidative stress in the epidermis as well as in
      melanoma cells and react with superoxide anion radicals to stimulate
      melanogenesis and to prevent peroxidative damage, respectively.

PMID- 7528238
TI  - Downregulation of human polymorphonuclear cell activities exerted by
      microorganisms belonging to the alpha-2 subgroup of Proteobacteria (Afipia felis
      and Rochalimaea henselae).
AB  - Intracellular pathogens have evolved effective mechanisms in order to survive in
      an intracellular environment, thus avoiding destruction by phagocytic cells. In
      this regard, a correlation between resistance to phagocytic killing and
      expression of pathogenic potency has been established. In this report, we have
      studied the interaction between human polymorphonuclear cells (PMN) and two gram
      negative microorganisms, Afipia felis and Rochalimaea henselae, which belong to
      the alpha-2 subgroup of the class Proteobacteria. A. falis has been previously
      proposed as the causative agent of Cat Scratch Disease (CSD), but several recent
      lines of evidence attribute a major role to R. henselae. Of note, CSD is a
      syndrome characterized by a chronic lymphoadenopathy, involving macrophages and
      endothelial cells with a progression towards a granulomatous process and/or
      angiogenesis. Since members of the alpha-2 subgroup of Proteobacteria have the
      property to survive intracellularly, we have evaluated the effects exerted by A.
      felis and R. henselae on human PMN in terms of chemotaxis locomotion,
      degranulation and oxidative metabolism. Results will show an impairment of PMN
      activities as a consequence of the challenge with both microrganisms. In
      particular, inhibition of PMN oxidative function occurred either as result of a
      direct exposure to both A. felis and R. henselae or when PMN were primed by
      bacteria for the N-formyl-methionyl-leucyl-phenylalanine enhancement of the
      oxidative burst. These findings may account for the ability of A. felis and R.
      henselae to survive within PMN as expression of a further mechanism of pathogenic
      potency, influencing also the nature and the evolution of inflammatory response
      in the lesion sites.

PMID- 7528240
TI  - Binding of keratin intermediate filaments (K10) to the cornified envelope in
      mouse epidermis: implications for barrier function.
AB  - The cornified envelope, a structure unique to keratinocytes, is a hallmark of
      their terminal differentiation and plays an important role in epidermal barrier
      function. Cornified envelope is formed through the action of a membrane
      associated transglutaminase, which covalently cross-links protein precursors into
      a highly insoluble network at the inner leaflet of the plasma membrane in
      granular keratinocytes and stratum corneum. Initial studies, using
      dansylcadaverine for enzyme-directed labeling of acyl-acceptor transglutaminase
      substrates in mouse epidermal homogenates identified a prominent 60-kDa
      substrate. Specific antibodies raised to this protein stained the cytoplasm of
      suprabasal cells of stratified squamous epithelia, whereas simple epithelia and
      nonepithelial tissues showed no staining. Immunoscreening of a cDNA expression
      library from adult mouse skin identified 18 positive clones. DNA sequencing of
      the largest clone (which hybridized to a keratinocyte-specific transcript of 2.0
      kb) showed greater than 99.5% homology with mouse keratin 10. Immunoelectron
      microscopy using anti-S60 and another antibody to keratin 10 showed specific
      binding to cornified envelope associated filamentous structures. Proteolytic
      fragments of purified cornified envelope from mouse epidermis showed reactivity
      to anti-S60. These data show that mouse keratin 10 is tightly bound to cornified
      envelope and may be a cross-linked substrate. The tight binding of keratin
      filaments and CE suggests a mechanism by which they might interact to enhance the
      structural integrity of the stratum corneum.

PMID- 7528242
TI  - Human dermal endothelial cells express membrane-associated mast cell growth
      factor.
AB  - Mast cell growth factor (MGF), a molecule that serves as a ligand for the
      receptor tyrosine kinase c-kit, is important in mast cell differentiation,
      migration, and activation. Previous studies of paraffin-embedded human skin using
      antibody to murine MGF and reverse transcription-polymerase chain reaction have
      demonstrated MGF protein and mRNA expression in keratinocytes and isolated dermal
      cells. We utilized a monoclonal antibody to human MGF to further define patterns
      of immunoreactivity in frozen specimens of neonatal and adult skin from normal
      individuals and from patients with urticaria pigmentosa. In addition to
      keratinocytes and isolated dermal cells in normal and urticaria pigmentosa skin,
      MGF was detected in cells lining superficial and mid-dermal vessels. Co
      expression of MGF and the vascular antigen CD31, and immunoelectron microscopy,
      identified MGF-positive cells as endothelial cells. Patterns of endothelial MGF
      expression were not influenced by mast cell degranulation and endothelial E
      selectin induction in vitro. By ultrastructure, unfixed specimens demonstrated
      MGF expression both within the endothelial cytoplasm and in association with
      lumenal, but not ablumenal, surfaces. Specimens fixed with Nakane's solution had
      diminished endothelial cytoplasmic MGF reactivity, but lumenal expression was
      maintained, suggesting persistence of a membrane-associated reactivity. MGF mRNA
      was also detected in cultured dermal microvascular endothelial cells using
      reverse transcription-polymerase chain reaction. These data establish human
      dermal endothelial cells as sites of MGF production and expression in human skin.
      Mast cell precursors must home to skin via vascular channels and differentiate in
      the immediate perivascular space. Thus, endothelial MGF may be an important
      determinant of adhesion and differentiation of mast cell progenitors expressing
      receptors for MGF.

PMID- 7528244
TI  - Delayed assembly of desmosomes in keratinocytes with disrupted classic-cadherin
      mediated cell adhesion by a dominant negative mutant.
AB  - We examined whether classic cadherins play a role in the formation of desmosomes
      using a mouse keratinocyte, PAMcN390 delta cell, which shows disrupted classic
      cadherin-mediated cell adhesion by introduction of a dominant-negative mutant of
      N-cadherin. The expression of the mutant did not alter that of endogenous E
      cadherin or desmoplakin. In control cells with functional classic cadherins, we
      observed redistribution of desmoplakin to cell-cell borders with insertions of
      keratin filaments at the contact sites as soon as 2 h after calcium elevation,
      after an earlier event of E-cadherin translocation to the cell-cell contact
      sites. In contrast, in the PAMcN390 delta cells, which showed retarded
      translocation of E-cadherin, the redistribution of desmoplakin and the
      rearrangement of keratin filaments were delayed as late as 24 h after the calcium
      elevation. The acquisition of Nonidet P-40 insolubility of desmoplakins also was
      found to be delayed in the PAMcN390 delta cells. These findings indicate that the
      disruption of classic cadherin affected the organization of desmosomes upon
      calcium elevation and suggest that the proper function of classic cadherins is a
      prerequisite for desmosome assembly in keratinocytes.

PMID- 7528243
TI  - Alteration in cell morphology triggers transforming growth factor-beta 1,
      collagenase, and tissue inhibitor of metalloproteinases-I expression in normal
      and hypertrophic scar fibroblasts.
AB  - Using immunocytochemistry and Northern blot analysis, we investigated the role of
      cell morphology and reorganization of the cytoskeleton in the expression of
      transforming growth factor-beta 1 (TGF-beta 1) in human dermal fibroblasts.
      Disruption of the cytoskeleton was induced by three different agents--trypsin,
      ethyl-eneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), or
      cytochalasin--and was confirmed by staining with rhodamine-labeled phalloidin.
      Immunocytochemical staining with antibodies specific for TGF-beta 1 revealed a
      cell-shape-related induction of TGF-beta 1. Northern blot analysis of total RNA
      showed a significant increase in the expression of TGF-beta 1 mRNA as early as 4
      h and peaking at 12 h after disruption of the cytoskeleton. Quantitative analysis
      of TGF-beta 1 mRNA expression at 4 h after treatment with trypsin, EGTA, or
      cytochalasin C showed increases of 2.6-, 3.3-, and 2.6-fold, respectively.
      Disruption of the cytoskeleton by trypsin, EGTA, or cytochalasin C increased mRNA
      for collagenase by 3.8-fold, 2.3-fold, or 2.5-fold, respectively. The expression
      of mRNA for tissue inhibitor of metalloproteinases I (TIMP-I) also showed a 3.2
      fold increase by trypsin, a 3.6-fold increase by EGTA, and a 2.5-fold increase by
      cytochalasin C. Cell-shape-related induction of TGF-beta 1, collagenase, and TIMP
      I genes appears to be selective, as the levels of mRNA for fibronectin and type I
      procollagen were not significantly altered. These data suggest that gene
      expression of TGF-beta 1, collagenase, and TIMP-I is governed by the status of
      the cytoskeleton microfilament organization, which may be a mechanism of gene
      regulation during cell division, migration, and differentiation, events
      fundamental to wound healing.

PMID- 7528245
TI  - Differential responsiveness of Langerhans cell subsets of varying phenotypic
      states in normal human epidermis.
AB  - Epidermal Langerhans cell heterogeneity is poorly understood with regard to
      phenotypic characteristics, such as the expression of human leukocyte antigen
      (HLA)-DR, integrin, and Fc receptor molecules, as well as functional
      characteristics, such as the ability to process and present antigens or produce
      cytokines during various phases of immigration and maturation. Technical
      limitations of Langerhans cell number have limited functional assays on putative
      Langerhans cell subsets in in vivo epidermis. Therefore, we used flow cytometry
      for simultaneous phenotypic and functional assessment at the single-cell level
      within the Langerhans cell population. Freshly isolated human epidermal cell
      suspensions were stained with a battery of monoclonal antibodies, including anti
      HLA-DR, -CD1a, -CD1c, -CD11c, -Fc gamma RII, and -Fc epsilon RI. Two distinct
      Langerhans cell subsets were identified by their different levels of HLA-DR
      expression. The DRHi subset expressed higher amounts of CD11c and exhibited
      greater cytoplasmic complexity and higher baseline calcium than the DRLo subset
      (p < or = 0.03 for each). Some subjects also expressed high levels of Fc epsilon
      RI in the DRHi, CD11cHi subset. To determine whether these phenotypic subsets may
      exhibit differential signal-transduction functional properties, Langerhans cells
      were partially enriched over Ficoll-Hypaque and their cytosolic mobilization
      after the addition of ionomycin was analyzed using the calcium indicator, indo-1,
      in conjunction with quantitative analysis of HLA-DR expression. By this real-time
      flow cytometric analysis, a new subpopulation was revealed within the DRLo
      Langerhans cell subset. This subset increased its cytosolic calcium concentration
      much more than the other two subsets (change in indo-1 blue:violet emission ratio
      of 37.33 +/- 2.34 in the Hi Flux DRLo subset versus 13.23 +/- 0.29 in the Lo Flux
      DRLo subset, and versus 7.6 +/- 2.99 in the Lo Flux DRHi subset). These data
      indicate that functional, as well as phenotypic, subsets of Langerhans cells
      exist within normal human epidermis. Their responses to physiologic stimuli may
      relate to maturational stage or the level of in vivo activation.

PMID- 7528246
TI  - Up-regulation of keratin 17 expression in human HaCaT keratinocytes by interferon
      gamma.
AB  - The immortalized human keratinocyte cell line HaCaT was used to assess the effect
      of interferon-gamma (IFN-gamma) on expression of keratin K17. Both IFN-gamma and
      K17 have been implicated in the pathophysiology of psoriasis. Western and
      quantitative enzyme-linked immunosorbent assay analyses demonstrated increasing
      induction of K17 protein by 48 h exposure to IFN-gamma at concentrations of 10,
      50, and 250 U/ml. At 50 U/ml IFN-gamma, immunohistochemical analysis revealed
      numerous K17-positive foci, whereas in situ hybridization demonstrated K17
      message in the majority of cells. In addition, at low (5 U/ml) concentrations of
      IFN-gamma, cell proliferation and protein synthesis decreased, as determined by
      3H-thymidine labeling and 14C-amino acid uptake. These data suggest that aberrant
      K17 expression observed in psoriatic lesions may be a consequence of IFN-gamma
      overexpression, and that the HaCaT cell line may be a useful in vitro model
      system to elucidate the underlying mechanisms.

PMID- 7528247
TI  - Isolation and long-term culture of human hair-follicle melanocytes.
AB  - We report a method to establish long-term cultures of melanocytes derived from
      human hair follicles. Normal human scalp was transected 1 mm below the epidermis,
      and hair follicles in the remaining dermis were isolated by collagenase
      treatment. Hair-follicle cell suspensions were prepared by
      trypsin/ethylenediamine tetraacetic acid treatment and cultured in a mixture of
      Eagle's minimum essential medium (supplemented with 12-O-tetradecanoyl-phorbol-13
      acetate and cholera toxin) and keratinocyte serum-free medium. After
      contaminating fibroblasts and keratinocytes were removed, cells with two distinct
      morphologies remained. These included large, dendritic and deeply pigmented
      cells, which did not proliferate and which disappeared by the third passage, and
      small bipolar cells, which initially were unpigmented, proliferated very rapidly,
      and became pigmented after the addition of 3-isobutyl-1-methylxanthine to the
      culture medium. Both cell types were melanocytes as confirmed by electron
      microscopy and by staining with antibodies to S-100, GD3, and melanosomal
      antigens. The availability of cultured hair-follicle melanocytes wil facilitate
      investigations of the role of these cells in normal and abnormal hair biology.

PMID- 7528252
TI  - Epitopes on surface antigens other than OspA can elicit a bactericidal effect
      against Lyme disease borrelias.

PMID- 7528249
TI  - Molecular subtyping of toxigenic Vibrio cholerae O139 causing epidemic cholera in
      India and Bangladesh, 1992-1993.
AB  - Since October 1992, > 150,000 cases of cholera have been reported from India and
      Bangladesh; the great majority of Vibrio cholerae isolates belong to the newly
      established serogroup O139. To better understand the interaction of genetic and
      epidemiologic factors responsible for their sudden appearance and rapid spread,
      representative toxigenic V. cholerae O139 isolates were molecularly characterized
      and compared with a set of toxigenic V. cholerae O1 and non-O1/non-O139 strains.
      DNA sequences of the cholera toxin B subunit gene and multilocus enzyme
      electrophoresis markers of V. cholerae O139 strains were identical to those of V.
      cholerae O1 isolates of the seventh pandemic. Two distinct ribotypes and four
      pulsed-field gel electrophoretic patterns were observed for O139 strains. V.
      cholerae O139 strains were very similar to V. cholerae O1 strains of the seventh
      pandemic but clearly different from the toxigenic V. cholerae strains of
      serogroups other than O1 and O139.

PMID- 7528248
TI  - Keratinocyte muscarinic acetylcholine receptors: immunolocalization and partial
      characterization.
AB  - We have reported previously that human keratinocytes synthesize and secrete
      acetylcholine and that muscarinic cholinergic drugs have effects on keratinocyte
      proliferation, adhesion, and migration. This study defines the location of
      muscarinic acetylcholine receptors in human epidermis and describes some
      pharmacologic and molecular properties of these receptors. Confocal microscopy
      employing the anti-muscarinic receptor monoclonal antibody M35 visualized the
      receptors in the intercellular areas of normal human epidermis. Using
      immunoelectron microscopy, the receptors appeared to be attached to the
      keratinocyte plasma membranes. Functional, high-density (Bmax = 8.3 nmol/2 x
      10(6) cells) and high-affinity (Kd = 21.5 nM) muscarinic receptors were
      demonstrated by saturable binding of the reversible radioligand [3H]quinuclidinyl
      benzilate to the surfaces of freshly isolated epidermal cells at 0 degrees C.
      Receptor proteins were separated by gel electrophoresis. An apparent isoelectric
      point of pH 4.3 was determined in immunoblots of sodium-cholate-solubilized
      receptors separated on isoelectric-focusing gels. Three protein bands, two at
      approximately 60 kDa and one at 95 kDa, were visualized in immunoblots of
      membrane-bound or solubilized receptors separated by sodium dodecylsulfate
      polyacrylamide gel electrophoresis. The covalent, irreversible ligand
      [3H]propylbenzilylcholine mustard confirmed these results. Thus, human
      keratinocytes express a heterogeneous population of muscarinic cholinergic
      receptors. Because human keratinocytes also express nicotinic cholinergic
      receptors, endogenously secreted acetylcholine may control different biologic
      processes in these cells by activating different types of their cholinergic
      receptors.

PMID- 7528250
TI  - Increased circulating cytokines, cytokine antagonists, and E-selectin after
      intravenous administration of endotoxin in humans.
AB  - Intravenous administration of endotoxin into humans causes transient fever,
      alteration in the number of circulating neutrophils, and transient release into
      plasma of cytokines, cytokine antagonists, and other cellular products. The
      release can be temporally differentiated, and the extent of release is dose
      dependent. By 1 h after endotoxin challenge, levels of tumor necrosis factor
      (TNF)-alpha and soluble TNF receptor increase; interleukin (IL)-6 and IL-8
      increase by 1.5 h, and IL-1 receptor antagonist, granulocyte colony-stimulating
      factor (G-CSF), granulocyte-macrophage colony-stimulating factor, and lactoferrin
      increase by 2 h. Increased G-CSF is temporally associated with neutrophilia and
      the appearance of band neutrophils. Increased plasma lactoferrin and altered
      neutrophil surface antigen expression suggest that intravascular activation of
      neutrophils has occurred. The level of soluble E-selectin (sE-sel), an adhesion
      molecule released from endothelial cells, is elevated at 4 h and remains elevated
      at 24 h. sE-sel levels increase with higher doses of endotoxin at 4, 6, and 24 h.

PMID- 7528251
TI  - A universal approach to bacterial molecular epidemiology by polymerase chain
      reaction ribotyping.
AB  - Oligonucleotide primers complementary to conserved regions of the 16S and 23S
      ribosomal RNA genes were used to amplify the 16S-23S intergenic spacer region of
      bacterial pathogens. The amplification patterns produced were compared for their
      potential use in molecular epidemiologic analysis. This method, polymerase chain
      reaction (PCR) ribotyping, was applied to isolates of Staphylococcus aureus,
      Enterococcus faecium, Escherichia coli, and Enterobacter species. Length
      polymorphisms in the amplified DNA distinguished unrelated strains of all
      bacteria. The banding patterns of 3 S. aureus isolates from the blood of 1
      patient on 3 consecutive days were identical. Plasmid analysis, biotyping, and
      antibiograms were also obtained on the Enterobacter isolates. All three of these
      methods showed considerable variability after in vitro passage of bacteria, but
      PCR ribotypes remained stable. Results demonstrate the utility of the conserved
      primers for PCR ribotyping, a widely applicable method for the molecular
      epidemiology of genetically diverse bacteria.

PMID- 7528254
TI  - Human immunodeficiency virus and Mycobacterium avium complex coinfection of
      monocytoid cells results in reciprocal enhancement of multiplication.
AB  - Disseminated Mycobacterium avium complex (MAC) infection is an important
      opportunistic infection in AIDS patients. Because cells of macrophage lineage are
      targets for both human immunodeficiency virus (HIV) and MAC, the monocytoid cell
      line U937 was coinfected with both pathogens. Coinfected cultures had increased
      HIV replication (more than threefold at day 6) and an increased percentage of HIV
      infected cells compared with cultures infected only with HIV. The kinetics of HIV
      replication were significantly increased in this coinfection system as measured
      by flow cytometry. When cells were infected concurrently, the rate of
      intracellular growth of MAC was not significantly affected. However, cells
      preinfected with HIV before infection with MAC showed significant enhancement of
      MAC growth compared with control cells. The kinetics of cell death were also
      increased in the coinfection system compared with singly infected controls. Thus,
      coinfection of monocytoid cells with HIV and MAC in vitro results in reciprocal
      enhancement of multiplication.

PMID- 7528253
TI  - In vitro inhibition of human immunodeficiency virus type 1 by a combination of
      delavirdine (U-90152) with protease inhibitor U-75875 or interferon-alpha.
AB  - Delavirdine (bisheteroarylpiperazine, U-90152), a nonnucleoside reverse
      transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1), was
      evaluated in a two-drug combination with recombinant human interferon-alpha (IFN
      alpha) or the peptidomimetic protease inhibitor U-75875 against HIV-1 replication
      in vitro. Viral growth was assayed in a CD4+ T cell line (H9) infected with
      HIVIIIB and in human peripheral blood mononuclear cells infected with the
      clinical isolate HIVJRCSF. Drug synergy, estimated by the combination index
      method and the method of Pritchard and Shipman, was observed when delavirdine was
      combined with U-75875 or IFN-alpha over a range of drug concentrations
      (delavirdine: 0.001, 0.003, 0.01, 0.03 microM; U-75875: 0.01, 0.03, 0.1, 0.3, 1.0
      microM; IFN-alpha: 2, 6, 17, and 50 or 10, 30, 100, and 300 IU/mL). The
      combinations showed no detectable drug antagonism or cytotoxicity. These in vitro
      synergy data support the potential use of delavirdine with either a protease
      inhibitor or IFN-alpha in patients with AIDS.

PMID- 7528255
TI  - [The rescue effect of FK506 in refractory rejection after cardiac
      transplantation].
AB  - The patient with dilated cardiomyopathy (NYHA class 4) under went cardiac
      transplantation at University of California, Los Angeles. Severe cardiac
      rejection was revealed one month after the transplantation. Steroid therapy was
      not effective, the rejection was resolved with OKT3 therapy and Anti-thymocyte
      globulin. Moreover, severe rejection was seen five months later. Steroid therapy
      was not effective. Cyclosporine administration was substituted for FK506 (0.02
      mg/kg/day). After the induction of FK506, the number of CD8 positive cells
      decreased and cardiac rejection was successfully resolved. As side effect of
      FK506, bradycardia with heart rate of 50/min for 4 minutes appeared. However, it
      was well-controlled when the trough level of FK506 was reduced to less than 8
      ng/ml.

PMID- 7528257
TI  - [Modality therapy of patients with non-resectable cancer using cytokines and
      antineoplastic agents].

PMID- 7528258
TI  - Calcium-binding properties of fetuin in fetal bovine serum.
AB  - Fetuin, an abundant protein in fetal bovine plasma, is the bovine homolog of
      human alpha 2HS glycoprotein (alpha 2HS). In spite of numerous studies, the
      biological functions of both proteins remain elusive. We now report the
      remarkable 45Ca-binding activity of fetuin in fetal bovine serum that has been
      blotted on a membrane after electrophoresis. The Ca-binding ability of the
      purified protein was analyzed by equilibrium dialysis, which revealed that bovine
      fetuin had multiple Ca-binding sites, one of which had a Kd of 0.95 x 10(-4) M.
      It was also shown that the Ca-binding activity of fetuin was greater than that of
      albumin in serum of the bovine fetus at the late gestational stage. Since fetal
      bovine serum contains not only a high concentration of fetuin but also a high
      concentration of Ca, it is possible that fetuin functions to maintain high levels
      of Ca in fetal serum via normalization of the concentration of Ca2+ ions.

PMID- 7528260
TI  - Evidence for superantigen activity of the Bel 3 protein of the human foamy virus.
AB  - The human foamy virus is a complex retrovirus that codes for several regulatory
      bel genes in addition to the conventional gag, pol, and env genes. The bel 3 gene
      is located in the 3' part of the viral genome comparable to that of the
      superantigen of the mouse mammary tumor virus. Superantigens bound to major
      histocompatibility complex (MHC) class II molecules have been shown to stimulate
      T cells in a V beta-specific manner. The recombinant Bel 3 protein purified to
      near homogeneity was assayed in vitro to determine whether or not it functions as
      a superantigen that stimulates human T lymphocytes expressing particular V beta T
      cell receptor (TCR) chains. Therefore, an analysis including all known human V
      beta elements was performed. The expression of different V beta chains of the TCR
      was analyzed by reverse transcription of the V beta RNAs and subsequent
      amplification of the corresponding V beta cDNA elements by polymerase chain
      reaction in unstimulated, phytohemaggluttinin (PHA)- and Bel 3-stimulated human T
      lymphocytes. In addition, eight monoclonal antibodies directed against particular
      V beta family members were used to determine any change in the expression of the
      remaining known V beta elements upon treatment with PHA and Bel 3. The
      comparative V beta-specific transcriptional analysis revealed that the in vitro
      expression of the V beta 18 chain was specifically and strongly expanded in Bel 3
      stimulated human T cells, a property characteristic for a superantigen.

PMID- 7528259
TI  - Immunoglobulin M and A antibodies to hepatitis C core antigen in chronic
      hepatitis C virus infection.
AB  - To determine the prevalence and clinical significance of IgM and IgA antibody to
      hepatitis C virus (HCV) core antigen in chronic HCV infection, sera from 47
      patients were tested for immunoglobulin class M (IgM) and immunoglobulin A (IgA)
      antibody to HCV core antigen by solid-phase enzyme-linked immunoassay using a
      recombinant core protein (aa1-150). Results were correlated with the clinical,
      biochemical and histological parameters, serum HCV RNA levels (determined by
      branched DNA signal amplification assay), and subsequent clinical response to
      interferon-alpha therapy. IgM anti-HCV core was detected in 11 patients (23.4
      percent). There was no correlation between the presence of IgM anti-HCV core and
      the clinical features (sex, age, mode of acquisition), biochemical parameters
      (serum ALT, AST, alkaline phosphatase, and albumin level), autoimmune markers
      [serum globulin levels, anti-nuclear antibody (+ at < 1:80 in 7/47 patients)],
      serum HCV RNA levels, subsequent response to interferon-alpha therapy, and the
      histological features. Immunoglobulin A anti-HCV core was not detected in any of
      the patients. The presence of IgM ant-HCV core in a proportion of patients with
      chronic HCV infection indicates that the presence of serum IgM anti-HCV core may
      not be unique to acute HCV infection.

PMID- 7528256
TI  - [Clinical study of hepatitis C].

PMID- 7528262
TI  - Effects of hepatitis C and B viruses infection on the development of
      hepatocellular carcinoma.
AB  - A case control study consisting of 102 patients with HCC, 102 sex-matched and age
      matched patients with nonhepatic disease, and 204 matched healthy controls was
      carried out to investigate the effect of hepatitis B virus (HBV) and hepatitis C
      virus (HCV) infection on the development of hepatocellular carcinoma (HCC). The
      prevalence of antibody to HCV (anti-HCV) in HCC (34.3%) was higher than in
      nonhepatic disease (10.7%, P < 0.001) or in healthy controls (2.4%, P < 0.001).
      The prevalence of hepatitis B surface antigen (HBsAg) in HCC (77.4%) was higher
      than in nonhepatic disease (16.6%, P < 0.001) or in healthy controls (19.6%, P <
      0.001). Anti-HCV positivity in nonhepatic disease was higher than in healthy
      controls (P < 0.01). Using patients with nonhepatic disease as controls, stepwise
      logistic regression analysis indicated that both anti-HCV (odds ratio, 3.4; 95%
      confidence interval, 2.1-5.6) and HBsAg (odds ratio, 5.6; 95% confidence
      interval, 3.6-8.5) are independent risk factors for HCC. Using healthy controls,
      the development of HCC was also strongly associated with anti-HCV (odds ratio,
      8.0; 95% confidence interval, 4.3-14.6) and HBsAg (odds ratio, 5.5; 95%
      confidence interval, 3.7-8.2). Calculation of incremental odds ratio indicated
      that there is no interaction between HBV and HCV. In conclusion, HBV and HCV are
      risk factors of HCC. They act independently and without interaction.

PMID- 7528261
TI  - Immune responses of blood donors to peptides of various lengths and those with
      genotypic sequence variations corresponding to the N-terminal portion of the core
      protein of hepatitis C virus.
AB  - Immune reactivities of blood donor sera with the peptides of various lengths (24,
      30, 40 and 50 mer) and those with genotypic sequence variations in the N-terminal
      portion of the core protein of hepatitis C virus (HCV) were compared by enzyme
      linked immunosorbent assays. It was found that a 40-mer oligopeptide (amino acids
      2-41) was recognized more frequently than other peptides even in serum samples
      that did not react with the C22-3 (core) by the recombinant immunoblot assay
      (RIBA-II). On the other hand, a 30-mer peptide (amino acids 1-30) had good
      correlation with viremia as confirmed by the polymerase chain reaction (PCR). In
      addition, four individuals showed the obvious differences in the immune responses
      to 30-mer oligopeptides representing the 4 genotypic variations. As a result,
      some samples that were PCR-positive but nonreactive by a commercial assay were
      found to react with short synthetic peptides in the N-terminal portion of the
      core protein.

PMID- 7528263
TI  - Allosteric regulation of the N-methyl-D-aspartate receptor-linked ion channel
      complex and effects of ethanol in ethanol-withdrawal seizure-prone and -resistant
      mice.
AB  - The effects of ethanol, glycine, and spermidine on the specific binding of [3H]MK
      801 were characterized in Triton-treated membranes prepared from the hippocampus
      and cortex of ethanol-withdrawal seizure-prone (WSP) and -resistant (WSR) mice.
      Glycine, an allosteric agonist at the NMDA receptor-linked ion channel complex,
      caused an increase in specific [3H]MK-801 binding to hippocampal membrane
      preparations. There were no significant differences in EC50 values between the
      selected lines for the effect of glycine (WSP, 391.7 +/- 48.4 nM; WSR, 313.4 +/-
      77 nM) in the presence of 10 microM NMDA or in the maximal response to the
      agonist (WSP, 1.75 +/- 0.26 pmol/mg of protein; WSR, 1.67 +/- 0.22 pmol/mg of
      protein). The EC50 values for the spermidine-induced increase in [3H]MK-801
      binding in membranes from hippocampus in the absence (WSP, 11.7 +/- 0.83 microM;
      WSR, 9.98 +/- 1.29 microM) or in the presence of 10 microM glycine and 10 microM
      NMDA (WSP, 2.1 +/- 0.35 microM; WSR, 2.37 +/- 0.42 microM) also did not differ.
      Similar results were obtained in cortical membranes. Saturation isotherms
      indicated that there was no difference in the density of [3H]MK-801 binding
      sites, or in their affinity for the radioligand, between the mouse lines. In
      addition, administration of ethanol by inhalation (24 h) to WSP and WSR mice did
      not cause an increase in the density of [3H]MK-801 binding sites, and there was
      no difference in the density or affinity of binding sites between the mouse
      lines.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528264
TI  - Characterization of the substance P (NK-1) receptor in tunicamycin-treated
      transfected cells using a photoaffinity analogue of substance P.
AB  - Chinese hamster ovary cells expressing the N-glycosylated substance P (NK-1)
      receptor were treated with the glycosylation inhibitor tunicamycin and
      photolabeled with 125I-Bolton-Hunter-p-benzoyl-L-phenylalanine8-substance P. Two
      radioactive proteins of M(r) 80,000 and 46,000, representing the glycosylated and
      nonglycosylated substance P (NK-1) receptor, respectively, were observed. The
      IC50 for the inhibition of photolabeling of both receptor forms was 0.3 +/- 0.1
      nM for substance P and 30 +/- 5 nM for neurokinin A (substance K). Thus,
      glycosylation of the substance P (NK-1) receptor has no detectable effect on the
      affinity of the substance P (NK-1) receptor for substance P or neurokinin A
      (substance K).

PMID- 7528265
TI  - Characterization of the excitotoxic potential of the reversible succinate
      dehydrogenase inhibitor malonate.
AB  - Although the mechanism of neuronal death in neurodegenerative diseases remains
      unknown, it has been hypothesized that relatively minor metabolic defects may
      predispose neurons to N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxic
      damage in these disorders. To further investigate this possibility, we have
      characterized the excitotoxic potential of the reversible succinate dehydrogenase
      (SDH) inhibitor malonate. After its intrastriatal stereotaxic injection into male
      Sprague-Dawley rats, malonate produced a dose-dependent lesion when assessed 3
      days after surgery using cytochrome oxidase histochemistry. This lesion was
      attenuated by coadministration of excess succinate, indicating that it was caused
      by specific inhibition of SDH. The lesion was also prevented by administration of
      the noncompetitive NMDA antagonist MK-801. MK-801 did not induce hypothermia, and
      hypothermia itself was not neuroprotective, suggesting that the neuroprotective
      effect of MK-801 was due to blockade of the NMDA receptor ion channel and not to
      any nonspecific effect. The competitive NMDA antagonist LY274614 and the glycine
      site antagonist 7-chlorokynurenate also profoundly attenuated malonate
      neurotoxicity, further indicating an NMDA receptor-mediated event. Finally, the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist NBQX (2,3
      dihydroxy-6-nitro-7-sulfamoylbenzo(f)-quinoxaline) was ineffective at preventing
      malonate toxicity at a dose that effectively reduced S-AMPA toxicity, indicating
      that non-NMDA receptors are involved minimally, if at all, in the production of
      the malonate lesion. We conclude that inhibition of SDH by malonate results in
      NMDA receptor-mediated excitotoxic neuronal death. If this mechanism of
      "secondary" or "weak" excitotoxicity plays a role in neurodegenerative disease,
      NMDA antagonists and other "antiexcitotoxic" strategies may have therapeutic
      potential for these diseases.

PMID- 7528266
TI  - Dexamethasone up-regulates a constitutive nitric oxide synthase in cerebellar
      astrocytes but not in granule cells in culture.
AB  - Treatment of rat cerebellar astrocyte-enriched primary cultures with
      dexamethasone enhances the nitric oxide-dependent cyclic GMP formation induced by
      noradrenaline in a time-(> 6 h) and concentration-dependent manner (half-maximal
      effect at 1 nM). Stimulation of cyclic GMP formation by the calcium ionophore
      A23187 is similarly enhanced. In contrast, cyclic GMP accumulation in cells
      treated with lipopolysaccharide is inhibited by dexamethasone. The potentiating
      effect of dexamethasone is prevented by the protein synthesis inhibitor
      cycloheximide and is not due to increased soluble guanylate cyclase activity.
      Agonist stimulation of [3H]arginine to [3H]citrulline conversion is enhanced by
      dexamethasone in astrocytes but not in cerebellar granule cells. These results
      indicate that glucocorticoids may up-regulate astroglial calcium-dependent nitric
      oxide synthase while preventing expression of inducible nitric oxide synthase and
      are the first report of a differential long-term regulation of the expression of
      neuronal and astroglial constitutive nitric oxide synthase activities.

PMID- 7528268
TI  - The dendritic peptide neurogranin can regulate a calmodulin-dependent target.
AB  - Neurogranin, a peptide capable of binding the calcium-poor form of calmodulin,
      was tested in vitro for its ability to modulate a typical calmodulin target. The
      target employed was the calcium/calmodulin-dependent form of nitric oxide
      synthase, which is produced by several different types of neurons. Neurogranin
      for the study was purified from perchloric acid-soluble calf brain proteins by a
      combination of calmodulin-Sepharose affinity chromatography and reverse-phase
      HPLC. The protocol yielded highly purified neurogranin that was active in assays
      using purified nitric oxide synthase. The titration of the enzyme activity with
      neurogranin demonstrated a concentration-dependent effect of the peptide on
      enzyme activation. Subsequent analysis of the ability of increased calcium
      concentrations to activate the enzyme was performed in the presence of different
      amounts of neurogranin. The effect of neurogranin on the calcium-dependent
      activation of the enzyme was to depress enzyme activity in the range of 0.2 to
      approximately 1 microM calcium. Treatment of the neurogranin peptide with protein
      kinase C eliminated its inhibition on nitric oxide synthase activation. Treatment
      of the protein kinase C-phosphorylated peptide with calcineurin did not restore
      the ability of neurogranin to inhibit enzyme activity, whereas treatment with
      alkaline phosphatase did restore this ability. These results suggest that
      neurogranin may serve as a member of a unique class of endogenous calmodulin
      inhibitor that functions to regulate the activation of calmodulin-requiring
      targets in neurons.

PMID- 7528269
TI  - 1'-(2-Phenyl-ethylene)-ditryptophenaline, a new dimeric diketopiperazine from
      Aspergillus flavus.
AB  - A new diketopiperazine dimer, 1'-(2-phenyl-ethylene)-ditryptophenaline [1], was
      isolated together with ditryptophenaline [2] from the fungus Aspergillus flavus.
      The structure of 1 was determined by analysis of spectroscopic data. In contrast
      to the structurally related substance-P antagonist WIN 64821 [3], both 1 and 2
      are weak substance-P inhibitors, indicating that stereochemistry at the position
      of dimerization is an important determinant of biological potency for these
      molecules.

PMID- 7528267
TI  - Inducible nitric oxide synthase in a human glioblastoma cell line.
AB  - Nitric oxide synthase (NOS) activity was induced in the cytosol of A-172 cells by
      treatment with lipopolysaccharide, tumor necrosis factor-alpha, and interferon
      gamma. A 130-kDa human inducible NOS (iNOS) protein was detected with anti-rat
      iNOS antibody by western blot analysis. Northern blot analysis showed that the
      iNOS mRNA was approximately 4.5 kb, using a cDNA fragment for human iNOS,
      isolated from stimulated A-172 cells by reverse transcriptase-PCR, as a probe.
      The mRNA was induced by interferon-gamma at a trace level, and its expression was
      synergistically enhanced by simultaneous addition of lipopolysaccharide, tumor
      necrosis factor-alpha, and, to a larger extent, interleukin-1 beta. The mRNA
      expression was blocked by coincubation with actinomycin D or cycloheximide.
      Furthermore, by transfecting the mouse iNOS gene promoter into A-172 cells,
      transcriptional activation of the iNOS gene was detected in these cells upon
      stimulation with lipopolysaccharide and cytokines. The pattern of promoter
      activation correlated well with that of iNOS mRNA expression upon stimulation.
      These data indicate that expression of iNOS is transcriptionally regulated in A
      172 cells. This process requires de novo protein synthesis with a mechanism
      similar to that in place in mouse macrophages.

PMID- 7528270
TI  - Cerebrospinal fluid concentrations of the complement MAC inhibitor CD59 in
      multiple sclerosis and patients with other neurological disorders.
AB  - Rodent oligodendrocytes have a unique susceptibility among glia to the lytic
      effects of complement, due in part to a deficiency in CD59 (protectin), a key
      surface inhibitor of the complement membrane attack complex (MAC). The
      possibility that shedding of CD59 by human oligodendrocytes contributes to
      complement-mediated oligodendrocyte injury in inflammatory demyelinating disease
      has been investigated by estimating levels of CD59 in cerebrospinal fluid samples
      from 12 patients with demyelinating disease of the central nervous system and 13
      with other neurological diseases. No significant differences were found between
      patients and controls, or between patients with active and those with clinically
      inactive demyelinating disease, providing no direct support for oligodendrocyte
      shedding of CD59 in multiple sclerosis.

PMID- 7528271
TI  - Multicyclic, dose-intensive chemotherapy supported by sequential reinfusion of
      hematopoietic progenitors in whole blood.
AB  - PURPOSE: To support multicyclic, dose-intensive chemotherapy, we assessed the
      effects of reinfusing hematopoietic progenitors collected at each cycle in
      leukapheresis product or whole blood. PATIENTS AND METHODS: Twenty-five patients
      with small-cell lung cancer (SCLC) were treated with six cycles of ifosfamide,
      carboplatin, and etoposide (ICE) with granulocyte colony-stimulating factor (G
      CSF) 300 micrograms/d subcutaneously (SC) on days 4 to 15. Hematopoietic
      progenitors collected during each cycle were reinfused on day 3 of the next
      cycle. Cohort 1 (n = 6) was treated every 3 weeks, with leukapheresis after 2
      weeks and cryopreservation of the leukapheresis product. Chemotherapy was given
      if the WBC count was > or = 3 x 10(9)/L and platelet count > or = 100 x 10(9)/L.
      Cohort 2 (n = 7) was treated every 2 weeks, with leukapheresis on day 1 of the
      next cycle and storage of the leukapheresis product at 4 degrees C. Cohort 3 (n =
      12) was treated every 2 weeks, with 500 to 750 mL of blood drawn by venesection
      on day 1 of the next cycle and stored at 4 degrees C. In cohorts 2 and 3,
      chemotherapy was given if the WBC count was > or = 3 x 10(9)/L and platelet count
      > or = 30 x 10(9)/L. Blood and leukapheresis products were assayed for
      hematopoietic progenitors. RESULTS: ICE chemotherapy with G-CSF was effective in
      mobilizing blood progenitors (median, 120-fold). Long-term cultures showed no
      evidence of stem-cell depletion. The cytotoxic dose-intensity of standard every-4
      weeks ICE is 100%. In the first three cycles, it was 134% (median) in cohort 1
      and 200% in cohorts 2 and 3 (P < .0001). Toxicity and supportive care
      requirements were not increased. CONCLUSION: The dose-intensity of ICE
      chemotherapy can be doubled by reinfusing hematopoietic progenitors collected by
      leukapheresis or venesection and stored at 4 degrees C.

PMID- 7528272
TI  - Prognostic significance of early serum tumor marker half-life in metastatic
      testicular teratoma.
AB  - PURPOSE: To determine whether the initial regression rates of serum tumor marker
      concentration (alpha-fetoprotein [AFP] and beta-human chorionic gonadotrophin
      [HCG]) were important prognostic factors after chemotherapy for germ cell tumors.
      PATIENTS AND METHODS: The analysis was confined to patients with at least two
      precise marker assay results between days 7 and 22 from start of platinum-based
      combination chemotherapy, with at least 7 days between markers. One hundred
      eighty-three patients were eligible and marker half-life (MHL) was evaluated for
      AFP in 142 and for HCG in 111 cases. MHL was calculated from the following
      formula: MHL = Ln1/2/G, where G was the gradient of the marker slope on a plot of
      Ln marker concentration versus time. MHL was regarded as prolonged if more than 3
      days for HCG or more than 7 days for AFP. RESULTS: The median AFP MHL was 6 days
      (range, 2.7 to 237) and the median HCG MHL was 2.6 days (range, 1.7 to 37.5).
      Forty-nine of 142 patients (35%) had a prolonged AFP MHL; 39 of 111 patients
      (35%) had a prolonged HCG-MHL. A prolonged MHL did not identify relapse after
      front-line chemotherapy. The positive predictive value of MHL tests in
      identifying patients who progressed after front-line therapy was 18% for HCG, 20%
      for AFP, and 18% for either marker. A prolonged MHL did indicate a higher risk of
      mortality (hazards ratio [HR], 2.4; P = .016), but again the positive predictive
      value of this test was only 23%. CONCLUSION: Early evaluation of MHL by this
      method does not predict patients at higher risk of progression after front-line
      chemotherapy, and also is a poor guide to long-term prognosis.

PMID- 7528273
TI  - Developmentally regulated lectins in Eimeria species and their role in avian
      coccidiosis.
AB  - Avian coccidiosis caused by Eimeria species is characterized by rather specific
      site infections of the intestine. We used hemagglutination and hemagglutination
      inhibition assays on various developmental stages of Eimeria tenella and on
      sporozoites of Eimeria acervulina and Eimeria maxima to assay for parasite
      lectins. Various monosaccharides, polysaccharides, and glycoproteins were used to
      demonstrate differences in sugar specificity of the lectins between these
      species. Surface lectins were found on the primary infective stage, i.e.,
      sporozoites, but not on merozoites or unsporulated oocysts. Also, there were
      differences in the specificities of the various sugar lectins among the different
      parasite species. Furthermore, there was a dose-dependent reduction of infection
      of tissue culture cells by sporozoites of E. tenella that were continuously
      exposed to fetuin, 1 of the specific inhibitors of the lectin. The results of our
      study are unique in that in 3 species of avian Eimeria all have a lectin on their
      sporozoites, but the lectins for each species have different sugar specificities.
      We hypothesize that these lectins found on the surface of the sporozoites may
      play a role in determining the site of infection within the intestine of the
      host.

PMID- 7528274
TI  - Preliminary characterisation of antigens recognised by monoclonal antibodies
      raised to Porphyromonas gingivalis and by sera from patients with periodontitis.
AB  - A panel of 15 monoclonal antibodies (MAbs) was raised to Porphyromonas gingivalis
      and used to characterise the antigens which they recognise by ELISA,
      immunofluorescence (IF), Western blotting and patient serum inhibition studies.
      All the MAbs were specific for P. gingivalis and did not recognise 24 other
      species. Eight MAbs gave bright ring-like staining patterns against the majority
      of serotypes of P. gingivalis tested by IF. The antibodies could be grouped into
      5 different antigen recognition profiles on Western blotting, and ELISA indicated
      that 8 of them bound to a capsular extract. Five antibodies bound to antigenic
      determinants recognised by sera from patients with periodonitis and 4 of these
      (1A1, 2B/H9, 3B1, 7D5) bound to a P. gingivalis 47kDa protease preparation on
      Western blotting. These antibodies are potentially useful for the purification
      and characterisation of biologically active components of P. gingivalis that are
      recognised by sera from patients with periodontitis.

PMID- 7528275
TI  - A novel voltage-dependent cation current in rat neocortical neurones.
AB  - 1. Using the whole-cell configuration of the patch-clamp technique, an unexpected
      voltage-dependent cation current (Icat) was recorded from acutely isolated rat
      neocortical neurones, the Na+, K+ and Ca2+ currents of which were
      pharmacologically suppressed. 2. Icat was activated at potentials more positive
      than -45 mV, displayed outward rectification, and deactivated with a slow voltage
      dependent time course causing prominent inward tail currents. 3. Activation of
      Icat was not dependent on Ca2+ influx or increases in cytosolic Ca2+, since it
      was not abolished by inorganic Ca2+ channel blockers or by internal Ca2+
      chelators. 4. Icat was reduced by tetraethylammonium at high concentrations, but
      not by 4-amino-pyridine, and proved to be insensitive to cation channel blockers
      such as Cs+, amiloride or gadolinium. 5. Ion substitution experiments revealed
      that the channel producing Icat was permeable to a number of monovalent cations,
      including K+, Cs+, Na+ and choline+, but not to the Cl-anion. 6. The features of
      Icat suggest that, in electrically active neurones, it should play a role in both
      the initial repolarization of membrane potential after strong depolarization and
      the generation of depolarizing after-potential.

PMID- 7528276
TI  - Regulation of intracellular pH in the smooth muscle of guinea-pig ureter: HCO3-
      dependence.
AB  - 1. HCO3(-)-dependent mechanisms involved in the regulation of intracellular pH
      (pHi) were characterized using double-barrelled pH-sensitive microelectrodes in
      smooth muscle cells of the isolated guinea-pig ureter. 2. Removal of external Cl-
      in the presence of CO2-HCO3- caused a transient alkalosis, consistent with the
      presence of Cl(-)-HCO3- exchange, before pHi slowly recovered. Recovery from
      acidosis in the presence of CO2-HCO3- was not affected, at a time when
      intracellular Cl- would have been maximally depleted, indicating that a counter
      transport of Cl- and HCO3- was not involved. The recovery was also not affected
      by amiloride, indicating that Na(+)-H+ exchange was not involved. 3. A transient
      hyperpolarization was associated with the recovery from acidosis in the presence
      of CO2-HCO3-, consistent with rheogenic coupling of Na(+)-HCO3- cotransport.
      However, depolarization caused by elevation of the extracellular potassium (K+o)
      concentration, which should favour inward transport by the rheogenic mechanism,
      caused a fall in pHi and decreased the rate of recovery from acidosis.
      Furthermore, ouabain abolished the transient hyperpolarization without affecting
      the recovery of pHi. It is concluded that Na(+)-HCO3- cotransport in the ureter
      is electroneutral. 4. Recovery from acidosis in the presence of CO2-HCO3- was
      insensitive to DIDS even after prolonged pre-equilibriation and extreme acidosis.
      The results suggest that Na(+)-HCO3- cotransport in the ureter is insensitive to
      DIDS and that Cl(-)-HCO3- exchange does not reverse to contribute to the
      extrusion of acid equivalents. A HCO3- conductance may account for the Na(+)
      independent, HCO3(-)-dependent recovery from extreme acidosis. 5. Recovery from
      experimentally induced alkalosis was inhibited by Cl(-)-free conditions and by
      DIDS, indicating that Cl(-)-HCO3- exchange was involved. 6. It is concluded that
      pHi in the smooth muscle of guinea-pig ureter is controlled by three transport
      mechanisms. By far the most important is an electroneutral Na(+)-HCO3-
      cotransporter. Na(+)-H+ exchange appears to play little role in the presence of
      the physiological buffer. Both of these mechanisms extrude acid equivalents and
      so protect the cell against its fairly substantial intrinsic intracellular acid
      loading. Cl(-)-HCO3- exchange, on the other hand, is stimulated by intracellular
      alkalosis to transport acid equivalents into the cell and so restore a more
      normal pHi.

PMID- 7528278
TI  - Antifertility effects of porcine zona pellucida-3 immunization using permissible
      adjuvants in female bonnet monkeys (Macaca radiata): reversibility, effect on
      follicular development and hormonal profiles.
AB  - Female bonnet monkeys Macaca radiata (n = 8, four per group) were immunized with
      purified 55 kDa glycoprotein from porcine zona pellucida (ZP3) and ZP3 conjugated
      to the beta subunit of human chorionic gonadotrophin (beta hCG) using adjuvants
      permissible for human use (alum, muramyl dipeptide and sodium phthalyl derivative
      of lipopolysaccharide). The animals were monitored for anti-ZP3 antibody titres,
      biweekly progesterone concentrations, menstrual cyclicity and status of
      fertility. All the animals generated a good anti-ZP3 antibody response, continued
      to have ovulatory cycles, remained infertile in the presence of high anti-ZP3
      antibody titres and showed no disturbance in cyclicity (except summer
      amenorrhoea). Examinations by laparoscope showed normal ovaries with developing
      follicles or corpora lutea on the surface. Fifty per cent of the animals
      conceived after a decline in antibody titres. Ovaries of animals that failed to
      regain fertility were examined for changes in morphology at times when anti-ZP3
      antibody titres in the circulation were low and following a booster when titres
      were high. None of the ovaries showed any sign of inflammation or lymphocytic
      infiltration. Follicles at different stages of development were seen in all of
      the ovaries. No significant reduction in the number of follicles, except in one
      monkey (MRA 178), was observed. There was no increase in the numbers of atretic
      or degenerating follicles. The results showed that ZP3 immunization with
      permissible adjuvants could be used for immunocontraception without obvious
      ovarian changes.

PMID- 7528277
TI  - Switching of mouse spermatogonial proliferation from the c-kit receptor
      independent type to the receptor-dependent type during differentiation.
AB  - Testicular cells composed mostly of germ cells and immature Sertoli cells from
      neonatal mice 2 and 5 days old were cultured to investigate germ-cell
      proliferation mediated by the c-kit receptor. The addition of antibody to block
      the interaction of the c-kit receptor with its ligand inhibited the proliferation
      of cultured spermatogonia from 5-day-old mice in a dose-dependent manner, but not
      from that of 2-day-old mice. The addition of anti-c-kit ACK2 monoclonal antibody
      also inhibited the proliferation of spermatogonia from 5-day-old mutant Sld/Sld
      mice but not of 5-day-old mutant Wv/Wv mice. The results indicate that c-kit
      positive type A spermatogonia in the testes of 5-day-old mice require steel
      factor (kit ligand) for their proliferation, whereas self-renewal and
      differentiation of c-kit-negative primitive type A spermatogonia in the testes of
      2-day-old mice do not.

PMID- 7528279
TI  - Distribution of carbohydrates in the zona pellucida of human oocytes.
AB  - The purpose of the present study was to investigate the distribution pattern of
      carbohydrates in the zona pellucida of human oocytes using lectins and ruthenium
      red as histochemical probes. For lectin analyses, oocytes that failed to undergo
      fertilization following in vitro insemination were collected, washed, fixed with
      glutaraldehyde and embedded in araldite. For ruthenium red labelling, the oocytes
      were fixed with glutaraldehyde containing ruthenium red, post-fixed with OsO4 and
      embedded in araldite. Araldite sections (1 micron) were de-resined with sodium
      methoxide, rehydrated, labelled with ten different biotinylated lectins as probes
      and avidin-biotin-peroxidase complex as visualant, and examined under a light
      microscope. The zonae pellucidae of all oocytes studied exhibited a common lectin
      binding pattern, expressed in intense binding of lectins from Concanavalia
      ensiformis (ConA), Lens culinaris (LCA), Ricinus communis (RCA-I), wheat germ
      agglutinin (WGA), and of succinylated WGA (S-WGA). Peanut lectin (PNA) bound to
      the zona pellucida only after neuraminidase treatment, whereas the lectins from
      Griffonia simplisifolia (GS-I), Dolichos biflorus (DBA), Ulex europhaeus (UEA-I)
      and soybean (SBA) did not bind at all. There was almost no binding of ruthenium
      red to the matrix of the zona pellucida. The results indicate that the human zona
      pellucida is characterized by normally exposed mannosyl, N-acetylglucosaminyl and
      beta-galactosyl residues. In addition, it contains masked beta Gal-(1-3)GalNAc
      sugar sequences that can be exposed only after removing terminal sialic acid
      residues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528280
TI  - FK506, an immunosuppressant, partially inhibits interleukin 6 production by
      adherent rheumatoid synovial cells.
AB  - OBJECTIVE: To investigate the effect of a new immunosuppressant, FK506, on
      interleukin 6 (IL-6) production by freshly prepared rheumatoid synovial cells.
      METHODS: Rheumatoid synovial cells were isolated from synovial tissue of patients
      with rheumatoid arthritis (RA) by using collagenase and DNase treatment. The
      surface phenotypes of the cells were analyzed by 2-color fluorescent analysis
      with FACScan. The levels of IL-6 in supernatant of cultured synovial cells were
      measured by enzyme immunoassay. RESULTS: The synovial cells used were mainly
      composed 32 +/- 1% of HLA-DR+/LeuM3+ cells and 53 +/- 6% of HLA-DR-/LeuM3-cells.
      These synovial cells spontaneously produced a large amount of IL-6 in culture.
      This spontaneous production of IL-6 was significantly inhibited by FK506 at the
      concentration of 10(-8) to 10(-6) M in a dose dependent manner. In the
      preincubation study, FK506 required more than 12 h to inhibit IL-6 production by
      synovial cells. CONCLUSION: These results suggest that FK506 may be beneficial
      for patients with RA via inhibiting IL-6 production in inflammatory joints.

PMID- 7528281
TI  - Inhibition of peptidylglycine alpha-amidating monooxygenase by N-substituted
      homocysteine analogs.
AB  - C-terminal amidation is a posttranslational modification found in many
      neuropeptides. Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the
      synthesis of the biologically essential C-terminal amide from a glycine-extended
      precursor peptide. Reported herein are the first potent inhibitors of PAM.
      Dipeptides containing a C-terminal homocysteine and an N-acylated hydrophobic
      amino acid were found to inhibit PAM with IC50s in the low nanomolar range.
      Inhibition potency was dependent on both the carboxylate and the thiolate
      functionalities of the homocysteine and on the hydrophobic groups of the second
      amino acid. The thiolate was postulated to produce high binding affinities
      through coordination with the active-site copper. The compound series also
      exhibited potent inhibition of PAM in rat dorsal root ganglion cells as
      demonstrated by a dose-dependent increase in the substance P-Gly/substance P
      ratio. These results indicate that the compounds have sufficient potency and
      intracellular bioavailability to aid future studies focused on neuropeptide
      function and the contributions of neuropeptides to various disease processes.

PMID- 7528282
TI  - Identification, synthesis, and characterization of a unique class of N-methyl-D
      aspartate antagonists. The 6,11-ethanobenzo[b]quinolizinium cation.
AB  - A series of novel N-methyl-D-aspartate antagonists acting at the phencyclidine
      site has been identified. Compound 2 has a Ki = 8 +/- 1 nM (vs
      [3H]thienylcyclidine, [3H]TCP) as a mixture of enantiomers. Resolution and
      further testing indicate that (-)-2, Ki = 4 +/- 0.7 nM, is a potent and selective
      TCP site ligand with neuroprotective activity in cultured neurons in the presence
      of excitotoxic concentrations of NMDA (IC50 = 26 nM). Compound (-)-2 is > 1000
      fold selective for the TCP site vs a panel of receptor types including opiate,
      adrenergic, serotonergic, dopamine, adenosine, dihydropyridine, and
      benzodiazepine and displays increased selectivity for the activated (open) NMDA
      receptor-ion channel complex vs PCP and MK801 as measured by patch recordings in
      cultured, voltage-clamped neurons. Highly enhanced "open-channel" selectivity
      leads to tentative classification of these ligands as uncompetitive vs NMDA.
      Ligands with these characteristics may enable deconvolution of the pharmacologic
      effects associated with typical noncompetitive NMDA antagonists. We report here
      on the identification, synthesis, and activity of compounds of this structural
      class.

PMID- 7528284
TI  - [Testis yolk sec tumor--a case report].
AB  - A 16-months old normal boy, a right testicular mass was discovered incidentally
      by his grandmother. Right inguinal orchiectomy was performed. Histological
      examination showed yolk sac tumor of testis. A preoperative alpha-fetoprotein
      level was markedly elevated at 13568.9 ng/ml, by the end of the twelve
      postoperative months, the serum alpha-fetoprotein levels was 118 ng/ml. The
      patient is doing well one-year postoperatively.

PMID- 7528286
TI  - Biochemical and histochemical studies of the effects of cerebral metabolism
      improving drugs on NADPH diaphorase activity in mouse brain.
AB  - The effects of cerebral metabolism-improving drugs on NADPH diaphorase activity
      in the mouse brain were studied, and we found that diaphorase activity in the
      post-mitochondrial fraction of brain homogenate was enhanced by idebenone in a
      concentration-dependent manner. Histochemical studies also indicated that
      diaphorase staining was intensified by idebenone at the same concentration. These
      results suggest that idebenone may stimulate the production of nitric oxide,
      probably through its direct action on nitric oxide synthase, thus producing its
      protective action on neurological disorders due to cerebral hypoxia or ischemia
      as a consequence of dilating the cerebral blood vessels.

PMID- 7528285
TI  - Tachykinin-induced contractions in the circular muscle of guinea pig ileum.
AB  - Actions of substance P (SP, 10(-9) to 10(-6) M), neurokinin A (NKA, 10(-9) to 10(
      6) M) and neurokinin B (NKB, 10(-10) to 10(-6) M) in the circular muscle of
      guinea pig ileum were investigated in segment and strip preparations, in which
      methacholine produced similar contractions. In the segment preparations, three
      tachykinins produced repeatedly occurring twitch-like contractions. Their
      efficacies were similar with the same maximal contractions, but their potencies
      were different (NKB > NKA = SP). Latency (38 sec) was observed before the
      initiation of contractions in response to NKA, but not to SP or NKB. Atropine
      (10(-6) M) and tetrodotoxin (3 x 10(-7) M) did not affect NKA-induced
      contractions, but inhibited SP- and NKB-induced contractions; the dose-response
      curves for SP and NKB were rightwardly shifted by atropine. The treatment with
      atropine brought out latency in the responses for NKB. In the strip preparations,
      SP did not substantially induce concentrations, but NKA and NKB produced twitch
      like contractions after latent periods of 28 and 36 sec, respectively. The
      efficacy of NKA was similar to that in segment preparations, while that of NKB
      was much lower in strip preparations. Unlike in segment preparations, atropine
      did not inhibit contractions induced by the two tachykinins in strip
      preparations. These results suggest that tachykinins induce contractions through
      myogenic and neurogenic mechanisms, the latter of which may be inoperative in
      strip preparations.

PMID- 7528287
TI  - A neutral sugar is responsible for serovar specificity of the antigenic
      determinant of Leptospira interrogans serovar canicola.
AB  - To provide information on the chemical structures of antigenic determinants of
      leptospira, glycolipids of Leptospira interrogans serovar canicola strain Hond
      Utrecht IV (Ut-IV) and its antigenic variant selected in the presence of a
      serovar-specific monoclonal antibody were compared physicochemically. Gas-liquid
      chromatography-mass spectrometry analysis revealed that the glycolipid of Ut-IV
      contained 6 neutral sugar species; rhamnose, mannose, galactose, glucose, and
      unknown sugars III and IV, in addition to unknown sugars I and II that had been
      previously reported. On the other hand, the glycolipid of the variant lacked
      unknown sugar III, suggesting that this sugar is responsible for the serovar
      specific antigenic determinant.

PMID- 7528288
TI  - [Effects of enterosorption on the activity of natural-resistance humoral factors
      in patients with burns].
AB  - The data suggesting the enterosorbent influence on the activity of proteolysis
      inhibitors and arginase, on the fibrin-fibrinogen and fibronectin decay products
      content, blood serum toxin fixating activity of injured with the burns were
      presented. The dependence of expression of mentioned indexes changes from the
      trauma severity in acute burn disease period was shown. The enterosgel
      application promotes the lowering of dystrophic degree severity, alike the hepar
      and fixed macrophage system load, the investigated indexes normalization
      acceleration, and patients condition improvement.

PMID- 7528283
TI  - Calcium and the endothelin-1 and alpha 1-adrenergic stimulated
      phosphatidylinositol cycle in cultured rat cardiomyocytes.
AB  - Cultured neonatal rat cardiac myocytes have been utilized as a model for the
      study of the effect of variations in cytoplasmic free Ca2+ on the activity of
      phospholipase C, a key enzyme in agonist-stimulated signal transduction through
      the phosphoinositide pathway. Cells prelabelled with [3H]inositol were exposed to
      various agents in an attempt to modulate the cytoplasmic free Ca2+ concentration
      and the formation of [3H]inositolphosphates (15-30 min) in the presence of Li+
      was taken as a measure of phospholipase C activity. Not the basal but the
      endothelin-1 (10(-8) M) induced [3H]inositolphosphate production (15 min) was
      stimulated 1.54- and 1.43-fold by A23187 (10 microM external Ca2+) and 50 mM K+
      (1.3 mM external Ca2+) treatment of cells, respectively. The phenylephrine (10(
      4) M) induced response was also stimulated (1.35-fold) by A23187, however it was
      43% inhibited by high K+. Ouabain (10 microM) treatment of cells did not affect
      either basal or agonist stimulated phosphoinositide turnover. On the other hand,
      total removal of external free Ca2+ by addition of 50 microM ethylene glycol
      bis(beta-aminoethyl ether) (N,N,N',N'-tetraacetic acid strongly inhibited (75%)
      the endothelin-1 induced but not the basal phospholipase C activity. Endothelin-1
      binding to its receptor was shown not to be inhibited by the absence of external
      Ca2+ while resynthesis of [3H]phosphatidylinositol 4,5-bisphosphate was not rate
      limiting under this condition. The lack of external Ca2+ eventually resulted in
      total standstill of the ET-1 induced PtdIns turnover after 30 min. Although not
      always as predicted, effects on basal and agonist-activated phospholipase C were
      observed too when cells were treated with low Ca2+ medium, Ca2+ entry blocker
      nifedipine (1 microM) or Ca(2+)-channel agonist Bay K8644 (1 microM) but most of
      these effects were only seen after 90 min incubation. Fluorometric (fura-2)
      measurements showed that total removal of external free Ca2+ for a short period
      decreased, while short exposure to high K+ increased cytoplasmic free Ca2+ but
      neither Ca2+ free buffer or nifedipine nor Bay K8644 had any effect. Furthermore,
      in saponin-permeabilized cardiomyocytes we could demonstrate that basal as well
      as GTP gamma S (30 microM) stimulated phospholipase C activity was strongly
      activated by free Ca2+ in the concentration range of 0.1-10 microM. We conclude
      that in the intact cardiomyocyte the signalling pathway through phospholipase
      C/phosphatidylinositol 4,5-bisphosphate, stimulated by agonist-receptor
      interaction that activates GTP-binding proteins as does GTP gamma S, is likely be
      a Ca2+ dependent process.

PMID- 7528289
TI  - Atrial natriuretic peptide reduces cyclic AMP by activating cyclic GMP-stimulated
      phosphodiesterase in vascular endothelial cells.
AB  - Bovine aortic endothelial cells contain cyclic GMP-stimulated phosphodiesterase
      (PDE) regulating intracellular cyclic AMP and cyclic GMP levels. To investigate
      the roles of this PDE isoform for cyclic AMP hydrolysis in intact endothelial
      cells (EC), we used an adenine prelabeling method to determine cyclic AMP
      accumulation in response to agents that might produce effects that increase
      cyclic GMP levels. Atrial natriuretic peptide (ANP), which dramatically increased
      cyclic GMP accumulation, reduced cyclic AMP in cultured EC from bovine aorta with
      or without addition of L-isoproterenol (L-ISO), whereas sodium nitroprusside
      (SNP) and 8-bromo cyclic GMP had no effect. The reduction in cyclic AMP by ANP
      was dose dependent (> or = 1.0 nM) and rapid (significant reduction was induced
      in < or = 15 s) and was abolished when EC were preincubated with 3-isobutyl-1
      methylxanthine (IBMX) and HL-725, both nonselective PDE inhibitors. ANP had no
      effects on adenylate cyclase activity, nor any direct effects on the activities
      of partially purified cyclic GMP-stimulated PDE isoform or cyclic AMP-specific
      isoform. However, cyclic AMP hydrolyzing activities of EC were enhanced when EC
      were pretreated with 0.1 microM ANP. ANP activates cyclic GMP-stimulated PDE and
      induces reduction of cyclic AMP accumulation in intact EC, which may modify
      cyclic GMP-dependent endothelial function involved in ANP.

PMID- 7528290
TI  - Effect of captopril treatment on total and central vascular capacitance in dogs
      with chronic heart failure.
AB  - Chronic rapid right ventricular pacing (RRVP) at 250 beats/min produces low
      cardiac output (CO) heart failure, marked reduction in total vascular
      capacitance, and a shift in volume centrally. The effect of converting enzyme
      inhibition with captopril on cardiac preload was investigated in this model of
      heart failure. Eight splenectomized dogs were treated with captopril (6.4 mg/kg
      daily) for 3 days before and 35 +/- 3 days (mean +/- SEM) after continuous RRVP
      was initiated and the outcome was compared with that of 5 untreated dogs
      subjected to RRVP for 32 +/- 3 days. Similar reductions in systemic arterial
      pressure (Psa) and CO and increases in right atrial pressure (Pra) and total
      peripheral resistance (TPR) were noted in both groups, however, pulmonary
      capillary wedge pressure (Ppcw) was higher in the untreated group (18.4 +/- 1.6
      vs. 12.1 +/- 2.0 mm Hg). Total vascular compliance and capacitance was estimated
      from mean circulatory filling pressures (Pmcf) at different blood volumes (TBV)
      during transitory cardiac arrests with acetylcholine (ACh). Pmcf after chronic
      RRVP was higher in untreated animals (12.6 +/- 1.9 vs. 8.4 +/- 0.7 mm Hg) and
      compliance was lower (1.9 +/- 0.2 vs. 2.6 +/- 0.2 ml/mm Hg/kg). Total vascular
      capacitance at a Pmcf of 6 mm Hg was lower in untreated animals (50 +/- 6 vs. 68
      +/- 3 ml/kg). Central vascular capacitance was also lower in untreated animals
      because Ppcw was higher and central blood volume (CBV) as a proportion of TBV was
      higher (21 +/- 3 vs. 15 +/- 2%). Four of 5 untreated and 1 of 8 treated dogs had
      severe ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528291
TI  - Functional characterization of an ex vivo preparation of atrial myocardium from
      children with congenital heart defects: sensitivity to tyramine and adrenoceptor
      antagonists.
AB  - Small pieces of atrial tissue removed from the cannulation site before
      cardioplegia were used to develop a method for studying adrenergic regulation of
      the myocardial contractile force in children operated on for congenital heart
      defects (CHD). We measured the development of the isometric force of contraction
      dT/dtmax (T'max). Reduction in basal contractility induced by the beta
      adrenoceptor antagonist timolol indicated that the myocardium was about half
      maximally stimulated by endogenous norepinephrine (NE), probably released from
      nerve endings by the electrical stimulation. The inotropic effect of endogenous
      NE could be further increased by tyramine (EC50 approximately 5 microM). A
      maximal concentration of tyramine increased T'max by a median of 62.5% above the
      basal level. Sequential blockade of the beta- and alpha 1-adrenoceptors after
      tyramine stimulation by timolol and prazosin, respectively, indicated that a near
      maximal response to combined adrenoceptor stimulation by endogenous NE was
      mediated by both beta-adrenoceptors (median 77%) and alpha 1-adrenoceptors
      (median 23%). The basal level of endogenous NE may conceal inotropic effects by
      exogenous alpha-agonists added to this type of preparation. This preparation is
      suitable for studying adrenergic regulation by reversing the effects of
      endogenous NE.

PMID- 7528292
TI  - Angiotensin blockade or calcium antagonists improve endothelial dysfunction in
      hypertension: studies in perfused mesenteric resistance arteries.
AB  - Endothelial regulation of peripheral vascular resistance is impaired in
      hypertension. We studied the effects of different antihypertensive therapies on
      endothelial function in perfused mesenteric resistance arteries. Spontaneously
      hypertensive rats (SHR) aged 7 weeks were treated with either the nonpeptidic
      angiotensin II (AII) receptor antagonist CGP 48369, the angiotensin-converting
      enzyme (ACE) inhibitor benazepril HCl, or the calcium antagonist nifedipine (each
      10 mg/kg/day orally, p.o.) for 8 weeks. All forms of therapy inhibited the
      increase in systolic blood pressure (SBP) to a comparable degree (18-23 mm Hg)
      and reduced but did not normalize medial hypertrophy in SHR. Changes in
      intraluminal vascular diameter to acetylcholine (ACh), norepinephrine (NE), and
      endothelin-1 (ET-1) were measured. Impaired endothelium-dependent relaxations to
      intraluminal ACh improved or normalized with all therapies, whereas the response
      to extraluminal ACh (which was unimpaired in SHR) remained unaffected. The
      endothelium-dependent inhibition of contractions to NE was lost in untreated SHR
      and improved or restored by antihypertensive therapy. In SHR, the sensitivity but
      not the maximal response of vascular smooth muscle (VSM) to ET-1 was
      paradoxically decreased. Antihypertensive therapy with CGP 48369, nifedipine, or
      benazepril HCl restored or increased the sensitivity to ET-1. Thus, chronic
      blockade of the renin-angiotensin system or voltage-operated calcium channels
      reduces BP and improves endothelial dysfunction in the resistance circulation of
      SHR. This may contribute to normalization of peripheral vascular resistance
      during antihypertensive treatment and improve local blood flow to vital organs.

PMID- 7528293
TI  - Effects of Zeneca ZD7288 in comparison with alinidine and UL-FS 49 on guinea pig
      sinoatrial node and ventricular action potentials.
AB  - ZENECA ZD7288 (4-(N-ethyl-N-phenyl-amino)-1,2-dimethyl-6-(methylamino) pyrimidium
      chloride) is a novel compound which we compared with alinidine and UL-FS 49
      (zatebradine) in guinea pig sinoatrial node (SAN) and papillary muscle
      preparations, using conventional microelectrode techniques. At low concentrations
      (1 x 10(-8)-1 x 10(-6) M), ZD7288 caused slowing of the diastolic depolarisation
      rate of SAN pacemaker cells, thus prolonging the diastolic interval and slowing
      the beating rate. Alinidine and UL-FS 49 also had qualitatively similar effects
      on diastolic depolarisation rate, but ZD7288 caused least prolongation of the
      action potential duration (APD) of SAN cells at the concentrations that had
      "selective bradycardic actions." ZD7288 affected the APs of ventricular cells in
      guinea pig papillary muscle only at relatively high concentrations (3 x 10(-6)M-1
      x 10(-4) M), which reduced plateau potential duration, although total APD was
      less affected. Reduced force of contraction (FOC) was also observed at these high
      concentrations; significant effects on AP Vmax were noted only at concentrations
      > or = 3 x 10(-5)M. Alinidine also had negative inotropic effects on papillary
      muscle, but its effects were noted at concentrations similar to those with
      bradycardic actions; in contrast, UL-FS 49 had marked positive inotropic actions
      and also increased ventricular APD within the bradycardic concentration range.
      These data provide a basis for the selective actions of ZD7288 on heart rate
      (HR).

PMID- 7528295
TI  - Effect of alpha 1-adrenergic receptor antagonists on susceptibility to malignant
      arrhythmias: protection from ventricular fibrillation.
AB  - alpha-Adrenergic receptor responsiveness has been reported to increase during
      myocardial ischemia, correlating with onset of malignant arrhythmias. If alpha
      adrenoceptor mechanisms play a significant role in induction of life-threatening
      arrhythmias, inhibition of these receptors with specific alpha-adrenoceptor
      antagonists should protect against disturbances in cardiac rhythm. To test this
      hypothesis, we induced ventricular fibrillation (VF) in 21 mongrel dogs with
      healed myocardial infarctions (MI) by 2-min coronary artery occlusion during
      exercise. On a subsequent day, the exercise plus ischemia test was repeated after
      the alpha 1-adrenoceptor antagonist prazosin HCl (0.5 mg/kg intravenously, i.v.;
      n = 14) or the alpha 1A-adrenergic receptor subtype antagonist WB4101 (2.0 mg/kg
      i.v., n = 9). Prazosin elicited a significant reduction in left ventricular
      systolic pressure (LVSP, control 157.0 +/- 6.5 vs. prazosin 118.5 +/- 2.7 mm Hg)
      and prevented arrhythmias in 13 of 14 animals (chi square p < 0.001). No other
      hemodynamic parameters, either before or during the coronary occlusion, were
      altered by prazosin. WB4101 did not alter any hemodynamic parameters either
      before or during coronary artery occlusion, yet prevented VF in 7 of 9 animals
      (chi square p < 0.025), delaying onset of malignant arrhythmias in the remaining
      animals. A second control exercise plus ischemia test reproducibly induced VF in
      all animals. Together these data demonstrate that alpha-adrenoceptor antagonists
      can prevent VF independent of hemodynamic changes. In particular, the data
      suggest that activation of the alpha 1A-adrenergic receptor subtype may
      contribute importantly to development of malignant arrhythmias.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7528294
TI  - Effect of atrial natriuretic peptide and calcium antagonists on platelet
      activating factor-induced contraction and intracellular calcium mobilization in
      rat mesangial cells.
AB  - We studied the effect of platelet-activating factor (PAF-acether) on rat
      mesangial cells (MC) and the intracellular mechanisms for PAF-acether-mediated MC
      activation. Contraction was measured as changes in planar cell surface area
      (PCSA), and intracellular free calcium concentration ([Ca2+]i) was measured as
      changes in the signal of the fluorescent indicator fura-2. PAF-acether induced a
      time- and dose-dependent reduction in PCSA and a dose-dependent increase in
      [Ca2+]i. Both phenomena were abolished by preincubation of the cells with the PAF
      acether-binding blockers L652,731 and BN 52021. TMB-8, an inhibitor of
      intracellular calcium mobilization, partially inhibited both the reduction in
      PCSA and the increase in [Ca2+]i, whereas the Ca2+ entry blocker verapamil
      completely inhibited the reduction in PCSA but only partially blocked the
      increase in [Ca2+]i. Atrial natriuretic peptide (ANP) produced a dose-dependent
      inhibition of PAF-acether-induced cell contraction, but its effect was not
      statistically related to changes in [Ca2+]i. These results show that PAF-acether
      induced MC contraction is associated with transient increases in [Ca2+]i, but the
      relaxing effects of ANP and verapamil may require additional physiologic
      interactions that involve mechanisms other than the [Ca2+]i transient.

PMID- 7528296
TI  - Pharmacologic and pharmacodynamic effects of the selective low Km cyclic AMP
      phosphodiesterase III inhibitors WIN 63291 and WIN 62582.
AB  - We describe the biochemical, pharmacologic, and in vivo pharmacodynamic profiles
      of two novel inhibitors of the cyclic GMP-inhibitable, low Km cyclic AMP
      phosphodiesterase (PDE) III; WIN 63291, a 6-quinolinyl analogue of the prototypic
      PDE III inhibitor milrinone and WIN 62582, an imidazopyridinone. Both WIN 62582
      and WIN 63291 competitively inhibit PDE III from rat, dog, and human heart and
      from rat and canine aorta with IC50 values of 5-37 and 55-80 nM, respectively;
      the IC50 values for milrinone ranged from 300 to 520 nM. WIN 62582 and WIN 63291
      are at least 1,000-fold selective for PDE III relative to inhibition of PDE
      isozymes I, II, IV, and V. We evaluated WIN 62582 and WIN 63291 in conscious rats
      and dogs after intravenous (i.v.) and oral (p.o.) administration. The dose of WIN
      62582 required to reduce mean arterial blood pressure (MAP) by 20% (ED20) in rats
      was 1.8 mg/kg, with a pharmacodynamic duration of action of approximately 2 h. In
      comparison, the estimated i.v. ED20 for WIN 63291 in rats was 0.4 mg/kg, with a
      pharmacodynamic duration of action > 6 h. In conscious dogs, the i.v. doses of
      WIN 62582 and 63291 required to increase left ventricular (LV)dP/dtmax
      significantly were 0.1 and 0.01 mg/kg, respectively. In dogs, WIN 63291 0.1 mg/kg
      p.o. increased LVdP/dtmax by 86% in 30 min; LVdP/dtmax remained increased by 60%
      for at least 6 h. In comparison, WIN 62582, 0.3 mg/kg p.o., increased LVdP/dt by
      56% in 30 min and remained increased by 40% at 6 h.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7528298
TI  - Alpha 1-adrenoceptor subtypes mediating adrenergic vasoconstriction in kidney,
      one-clip Goldblatt and deoxycorticosterone acetate-salt hypertensive rats.
AB  - We characterised the functional alpha 1-adrenoceptors involved in mediating
      adrenergic vasoconstrictor responses in kidney of two-kidney one-clip (2K1C)
      Goldblatt and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In
      sodium pentobarbital-anaesthetised rats, frequency- and dose-dependent renal
      vasoconstrictor responses were obtained by direct electrical renal nerve
      stimulation, close renal arterial administration of phenylephrine (PE), and
      methoxamine. Administration of amlodipine, a dihydropyridine calcium channel
      antagonist (bolus dose of 200 and 400 micrograms/kg and an infusion of 50 and 100
      micrograms/kg/h, respectively) and the alpha 1-adrenoceptor antagonist 5
      methylurapidil (5 micrograms/kg plus 1.25 micrograms/kg/h and twice this dose)
      suppressed renal nerve-, PE-, and methoxamine-induced vasoconstrictions 14-70% (p
      < 0.05-0.001) in 2K1C Goldblatt and DOCA-salt hypertensive rats. The alpha 1B
      adrenoceptor alkylating agent, chloroethylclonidine (5 micrograms/kg plus 1.25
      micrograms/kg/h and twice this dose) caused significant attenuation (p < 0.001)
      of renal nerve-induced vasoconstriction by 19-23% in DOCA-salt hypertensive rats
      but did not affect PE- and methoxamine-induced vasoconstriction in either 2K1C
      Goldblatt or DOCA-salt hypertensive rats. In contrast, in 2K1C Goldblatt rats
      vasoconstrictor responses were potentiated by renal nerve stimulation and
      methoxamine. The data show that the functional renal postjunctional alpha 1
      adrenoceptors on the vasculature of both hypertensive models are primarily of the
      alpha 1A-subtype, as reflected by their sensitivity to amlodipine and 5
      methylurapidil. Moreover, an interaction appears to occur between the alpha 1
      adrenoceptor subtypes at renal vessels in 2K1C Goldblatt hypertensive rats.

PMID- 7528299
TI  - Changes in plasma norepinephrine concentration and thrombocyte alpha 2
      adrenoceptor density during long-term antihypertensive therapy with nitrendipine
      and captopril.
AB  - Antihypertensive drugs influence the sympathetic nervous system in different ways
      that may cause adverse or beneficial effects. We treated 48 hypertensive patients
      with either nitrendipine (10-20 mg twice daily, b.i.d.) or captopril (25-50 mg
      b.i.d.) for 16 weeks to evaluate changes in plasma catecholamines, platelet alpha
      2- and lymphocyte beta 2-adrenoceptors. Blood pressure (BP) decreased from 153/95
      to 135/87 mm Hg with captopril and from 155/99 to 137/89 mm Hg with nitrendipine.
      Treatment with nitrendipine significantly stimulated plasma norepinephrine (NE)
      from 327 +/- 37 to 446 +/- 50 pg/ml, and treatment with captopril resulted in a
      significant reduction in platelet alpha 2-adrenoceptor density from 265 +/- 39 to
      171 +/- 26 fmol/mg protein. Despite having equal BP-lowering properties,
      captopril and nitrendipine have different effects on the sympathetic nervous
      system. Stimulation of plasma NE during long-term treatment with nitrendipine may
      contribute to possible adverse effects, whereas reduction in alpha 2
      adrenoceptors induced by captopril may contribute to the vasodilating effect of
      angiotensin-converting enzyme (ACE) inhibition.

PMID- 7528297
TI  - Electrophysiologic effects of alprafenone on canine cardiac tissue.
AB  - We studied the actions of the propafenone derivative alprafenone on transmembrane
      action potentials (APs) of canine Purkinje fibers (PF) and ventricular and atrial
      muscle. In PF with normal maximum diastolic potentials (MDPs), alprafenone (5 x
      10(-8)-1 x 10(-6) M) produced concentration-dependent decreases in AP amplitude
      (APA), Vmax, AP duration (APD), and conduction velocity. The effects on Vmax were
      use dependent. The decrease in PF APD was the result of the drug's action on the
      slope of phase 2. In contrast to its effect on PF, alprafenone induced a
      significant increase in APD in ventricular epicardial and endocardial muscle and
      had no effect on atrial APD. In PF, alprafenone prolonged the effective
      refractory period (ERP) with respect to APD, and at high [K+]0, prolonged
      refractoriness beyond repolarization. Alprafenone decreased Vmax and slow
      response APA. It had no effect on normal automaticity or isoproterenol (ISO)
      induced automaticity, but significantly suppressed BaCl2-induced abnormal
      automaticity at low levels of membrane potential. Alprafenone inhibited both
      early and delayed afterdepolarizations and eliminated triggered activity. We
      conclude that alprafenone's range of actions is consistent with that of other
      effective antiarrhythmic drugs and is very similar to that of propafenone.

PMID- 7528300
TI  - Role of adenosine in vasodilation of epimyocardial coronary microvessels during
      reduction in perfusion pressure.
AB  - Previous studies in which an isolated heart or in situ constant pressure
      preparation was used suggested a minimal role for adenosine in autoregulatory
      control of coronary circulation. These results, however, are controversial, and
      the role of adenosine in autoregulation of flow in heart is uncertain. To test
      the hypothesis that adenosine mediates microvascular dilation in response to
      reduction in perfusion pressure (PP), we performed experiments in 41 open-chest
      chloralose-anesthetized dogs. Internal diameters (ID) of epicardial small
      arterioles < 100 mumol were measured with an intravital microscope and
      stroboscopic epiillumination synchronized to cardiac cycle. PP was reduced by
      graded stenoses of the left anterior descending coronary artery (LAD, mild
      stenosis PP = 60 mm Hg; critical stenosis PP = 40 mm Hg) and complete occlusion.
      8-Phenyltheophylline (8-PT 10 microM) or adenosine deaminase (ADA 10 U/min) was
      topically superfused onto the heart. Arteriolar dilation induced by topically
      applied adenosine < or = 10 microM was completely blocked by 8-PT. Without 8-PT
      (vehicle group), mild critical stenosis and complete occlusion caused arteriolar
      dilation (percentage of change in diameter 8.6 +/- 2.6, 16.0 +/- 2.7, and 13.6 +/
      4.8%). 8-PT did not inhibit this dilation (8.5 +/- 2.8, 16.1 +/- 4.6, 15.1 +/-
      5.7%, NS vs. vehicle group). Topically applied ADA significantly inhibited
      intravenously (i.v.) administered adenosine-induced arteriolar dilation. Without
      ADA, arteriolar dilation occurred (16.6 +/- 3.0, 28.2 +/- 4.3, 15.4 +/- 6.2%, at
      each PP). However, ADA did not inhibit dilation induced by gradual stenoses (10.6
      +/- 1.4, 24.2 +/- 4.3, 17.5 +/- 6.9%, at each PP, NS vs. vehicle group).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7528302
TI  - No functional involvement of 5-hydroxytryptamine1A receptors in nitric oxide
      dependent dilatation caused by serotonin in the human forearm vascular bed.
AB  - The vascular effects of serotonin (5-hydroxytryptamine, 5-HT) are complex and
      heterogeneous. In human forearm, we showed that low doses of 5-HT cause marked
      but transient vasodilatation followed by a persistent vasodilator response. In in
      vitro and in animal experiments, 5-HT induced release of nitric oxide (NO)
      through stimulation of endothelial 5-HT1-like receptors. In the present study, we
      investigated involvement of the "NO pathway" and possible involvement of the 5
      HT1A receptor subtype in 5-HT-induced persistent vasodilator response. In 8
      healthy volunteers, we infused 5-HT (0.1, 0.3, and 1 ng/kg/min) and the selective
      5-HT1A receptor agonist flesinoxan (15, 45, and 150 ng/kg/min) intraarterially
      (i.a.) with NG-monomethyl-L-arginine (L-NMMA 30 micrograms/kg/min) or saline.
      Forearm blood flow (FBF) was measured by automated R-wave-triggered venous
      occlusion plethysmography. Forearm vascular resistance (FVR) was derived from
      simultaneously recorded i.a. blood pressure (BP) and FBF. 5-HT dose-dependently
      decreased FVR (p < 0.001). The persistent vasodilator response to 5-HT appears to
      be mediated by NO release, as suggested by its complete abolition by L-NMMA (p <
      0.001). Flesinoxan decreased FVR slightly, but only at high doses (p < 0.05). The
      present findings indicate that 5-HT1A receptors are not functionally involved in
      5-HT-mediated vasodilatation in human forearm.

PMID- 7528301
TI  - Systemic and coronary hemodynamic effects of repetitive cocaine administration in
      conscious dogs.
AB  - The cardiovascular actions of cocaine are complex, and previous studies suggest
      that tachyphylaxis to the positive chronotropic and pressor effects of cocaine
      may develop after repetitive administration. We examined changes in systemic and
      coronary hemodynamics when single or multiple doses of intravenous (i.v.) cocaine
      were administered to conscious dogs. Dogs were chronically instrumented for
      measurement of aortic blood pressure (BP) and left ventricular pressure (LVP), LV
      dP/dtmax and dP/dt50, subendocardial segment length (%SS), diastolic coronary
      blood flow (CBF) velocity, and cardiac output (CO). Myocardial oxygen consumption
      was estimated by the pressure-work index (PWI). In one series of experiments, a
      single dose of cocaine (0.1, 0.2, 0.4, 0.8, or 1.6 mg/kg) was administered on 5
      consecutive days in random fashion and peak changes in systemic and coronary
      hemodynamics were recorded. These doses were then randomly repeated in a second
      group of experiments with a 1-h interval between doses on the same day. Peak and
      steady-state changes in cardiovascular variables were recorded within and between
      each dose, respectively. In other experiments, higher doses of cocaine (0.8 or
      1.6 mg/kg; separate groups) were administered four times at 1-h intervals in the
      same dogs and peak and steady-state changes in hemodynamics were determined.
      Cocaine caused dose-related increases in heart rate (HR), mean arterial pressure
      (MAP), LV systolic pressure (LVSP) and end-diastolic pressure (LVEDP), PWI, CO,
      and diastolic coronary vascular resistance and decreases in %SS when administered
      on different days. Cocaine also caused significant increases in baseline HR, MAP,
      LVSP, and PWI between doses given on the same day at 1-h intervals, but the
      absolute value of the peak response to cocaine of these hemodynamic parameters
      was independent of dosing regimen. These results were confirmed when we
      administered four doses of 0.8 mg/kg cocaine at 1-h intervals. The results
      indicate that baseline changes in systemic hemodynamic variables are a
      predominant feature of repetitive administration of lower doses of cocaine (< or
      = 0.8 mg/kg), but administration of higher doses of cocaine (> or = 8 mg/kg) at 1
      h intervals caused tachyphylaxis to the hypertensive actions and myocardial
      oxygen consumption effects of cocaine.

PMID- 7528304
TI  - Magnesium modulates endothelial dysfunction produced by elevated glucose
      incubation.
AB  - In aorta taken from diabetic rabbits studied ex vivo or from normal rabbits
      exposed to increased glucose for 6 h in vitro the endothelium-dependent
      relaxation to acetylcholine (ACh) is impaired. Magnesium ion concentration
      influences vascular smooth muscle (VSM) contractility, endothelium-dependent
      relaxing factor (EDRF) release and prostaglandin production. We wished to
      determine the effects of changes in magnesium ion concentration on the
      abnormality induced by elevated glucose concentration (44 mM) in the endothelium
      dependent responses observed in isolated rabbit aorta. In phenylephrine (PE)
      precontracted vessels, with physiologic salt solution (PSS) containing 1.2 mM
      magnesium, endothelium-dependent relaxation and endothelium-independent
      contraction to ACh was not affected by incubation in elevated glucose (44 mM),
      indomethacin (10(-5) M) treatment, or both. In solution containing 0.6 mM
      magnesium, the endothelium-dependent relaxation to ACh was impaired in elevated
      glucose. Indomethacin treatment did not affect endothelium-dependent relaxation
      in the control solution but partially restored the response to ACh in elevated
      glucose. Under basal conditions and in the presence of nitric oxide (NO) synthase
      inhibition, ACh induced a contraction. In low magnesium-containing medium, this
      contraction was potentiated by the presence of endothelial cells in control (5.5
      mM) and even more in elevated glucose concentration (44 mM). The endothelium
      dependent contractions were abolished by pretreatment with indomethacin. However,
      in control magnesium conditions (1.2 mM), an endothelium-dependent component to
      the ACh contraction was observed only in elevated glucose concentration.
      Responses to sodium nitroprusside (SNP), KCI, and serotonin, and the
      concentration to ACh (in the absence of endothelium) were not influenced by
      elevated glucose, indomethacin treatment, or both.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7528303
TI  - Effect of low-dose treatment with perindopril on cardiac function in stroke-prone
      spontaneously hypertensive rats: role of bradykinin.
AB  - Angiotensin-converting enzyme (ACE) inhibitors can improve cardiac function
      independent of their blood pressure (BP)-lowering actions. We investigated the
      effect of chronic subantihypertensive ACE inhibitor treatment on functional and
      biochemical cardiac parameters in stroke-prone spontaneously hypertensive rats
      (SHRSP). Animals were treated in utero and subsequently to age 20 weeks with the
      ACE inhibitor perindopril (0.01 mg/kg/day). The contribution of endogenous
      bradykinin (BK) potentiation to the actions of the ACE inhibitor was assessed by
      cotreatment with the BK beta 2-receptor antagonist Hoe 140 (500 micrograms/kg/day
      subcutaneously, s.c.) from age 6 to 20 weeks and by measurement of myocardial
      prostacyclin and cyclic GMP concentrations. Chronic low-dose perindopril
      treatment had no effect on development of hypertension and left ventricular
      hypertrophy (LVH), but perindopril improved cardiac function, as demonstrated by
      increased LV pressure (LVP) (19.4%) and LVdp/dtmax (27.8%) but no change in heart
      rate (HR). The activities of lactate dehydrogenase (LDH) and creatine kinase (CK)
      as well as lactate concentrations in the coronary venous effluent were reduced by
      39.3, 50, and 60.6%, respectively. Myocardial tissue concentrations of glycogen
      and the energy-rich phosphates ATP and CK were increased by 16.3, 33.1, and
      28.2%, respectively. All ACE inhibitor-induced effects on cardiac function and
      metabolism were abolished by concomitant chronic BK receptor blockade. Cardiac
      prostacyclin concentrations were threefold elevated in perindopril-treated
      animals whereas cardiac cyclic GMP concentration remained unchanged as compared
      with that of controls. Our data demonstrate that chronic low-dose ACE inhibitor
      treatment can improve cardiac function and metabolism by potentiating endogenous
      BK.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528306
TI  - Thromboxane receptor antagonist BMS-180291, but not aspirin, reduces the severity
      of pacing-induced ischemia in dogs.
AB  - We determined the effect of thromboxane A2 (TXA2) prostaglandin endoperoxide (TP)
      receptor antagonism, using BMS-180291 or aspirin, on the severity of pacing
      induced ischemia in anesthetized dogs. Thromboxane receptor antagonists may not
      only have antithrombotic activity, but may also have direct cardioprotective
      effects, unlike aspirin. Left anterior descending coronary artery (LAD) stenosis
      was adjusted so that a significant (10-12 mV) ST segment elevation was observed
      only when superimposed on atrial pacing. Each heart was subjected to 5-min
      episodes of pacing-induced ischemia 10, 40, and 70 min after initiation of BMS
      180291 (1 mg/kg + 1 mg/kg/h) or vehicle. In the vehicle group, ST segment
      elevation was reproducible at all pacing-induced ischemia episodes, whereas BMS
      180291 significantly reduced it by 30% at the later ischemia episodes. This
      reduction in ST segment increase was not accompanied by alterations in regional
      myocardial blood flow (RMBF) nor in hemodynamic status. Aspirin in the same model
      [10 mg/kg intravenously (i.v.) given 10 min before pacing-induced ischemia] did
      not significantly reduce ST segment elevation, indicating a lack of protective
      effect in this model. Thromboxane receptor blockade appears to protect myocardium
      subjected to pacing-induced ischemia, an effect not produced by aspirin.

PMID- 7528305
TI  - Value of different clinical and biochemical correlates to assess angiotensin
      converting enzyme inhibition.
AB  - In a double-blind study, we compared the value of different approaches to assess
      blockade of angiotensin (Ang) II generation in 10 normal volunteers treated with
      the new Ang-converting enzyme (ACE) inhibitor temocapril. Plasma concentration of
      the diacid active metabolite of temocapril, plasma Ang I and II levels, plasma
      ACE activity, and inhibition of the pressor response to repeated intravenous
      (i.v.) doses of Ang I were measured before and repeatedly after different doses
      of tempocapril or placebo. In vivo ACE activity, estimated by the plasma Ang
      II/Ang I ratio, correlated well with temocapril diacid concentration (r = 0.85, n
      = 148) and with systolic and diastolic blood pressure (SBP, DBP) responses to Ang
      I (r = 0.76 and r = 0.79, n = 148). SBP and DBP responses to Ang I were also
      strongly related to temocapril diacid concentration (r = -0.81 and r = -0.88, n =
      148). ACE activity measured in vivo reliably predicts the decrease in Ang
      dependent BP to be achieved by ACE inhibitors.

PMID- 7528308
TI  - Effects of the combined 5-hydroxytryptamine2 receptor and Ca2+ channel antagonist
      LU49938 on the responsiveness of isolated porcine coronary arteries with and
      without endothelium.
AB  - We performed experiments to determine the effects of the combined 5
      hydroxytryptamine2 (5-HT2) receptor and Ca2+ channel antagonist LU49938 ((2S)-5
      [N-methyl-N-(n-hexyl)]amino-2-isopropyl-2(3.4.5-trimethoxy phenyl)-valeronitril
      hydrochloride) on vascular smooth muscle (VSM) and endothelium in isolated
      porcine coronary arteries. Rings with and without endothelium were suspended in
      conventional organ chambers for measurement of isometric force. LU49938 inhibited
      contractions evoked by serotonin, norepinephrine (NE), and prostaglandin F2 alpha
      (PGF2 alpha) in a concentration-dependent and noncompetitive manner. The lower
      concentrations of LU49938 (10(-7) and 10(-6) M) did not affect contractions to
      serotonin in the presence of ketanserin. However, a higher concentration of
      LU49938 (10(-5) M) significantly decreased the concentration-response curve to
      the monoamine in the presence of ketanserin. These finding suggest that LU49938
      has a dual inhibitory effect on contractions: selective inhibition of 5-HT2
      receptor and nonselective inhibition of the contractile process in VSM. The
      mechanism of this nonselective inhibition of VSM is likely to be related to
      inhibition of Ca2+ entry because LU49938 inhibited responses to several agonists.
      The time course and degree of relaxation caused by LU49938 were comparable in
      rings with and without endothelium in control solution or after incubation with
      nitro-L-arginine and/or indomethacin. LU49938 did not affect endothelium
      dependent relaxations induced by serotonin and bradykinin. These results suggest
      that LU49938 does not affect endothelium-dependent responses in porcine coronary
      artery.

PMID- 7528309
TI  - [Palliative medicine: does it have a place in a curriculum?].

PMID- 7528307
TI  - Noninvasive assessment of regional arteriolar and arterial dilating properties of
      lisinopril in healthy volunteers.
AB  - The effects of single oral doses of lisinopril (5 and 20 mg) on systemic and
      regional hemodynamics were investigated noninvasively in a placebo-controlled,
      randomized, double-blind, cross-over study of 6 healthy male volunteers.
      Lisinopril induced a dose-dependent (significant after 20 mg) and long-lasting (<
      or = 8 h) decrease in mean arterial pressure (MAP, approximately 11% after 20 mg)
      that was related to a decrease in total peripheral resistance (TPR), because
      simultaneously heart rate (HR) and cardiac output (CO) were unchanged. Brachial
      artery flow (+42 and +47% after 5 and 20 mg, respectively) and diameter (+8 and
      +9%) increased significantly, whereas brachial vascular resistance (-31 and -38%)
      decreased significantly from 2 to 8 h after drug intake. Common carotid artery
      flow (+20 and +24%) also increased significantly, whereas corresponding
      resistance (-18 and -26%) decreased significantly during the same period.
      Finally, CO was significantly redistributed toward the brachial and, to a lesser
      extent, the carotid vascular beds after both doses of lisinopril. We conclude
      that in healthy subjects lisinopril, at non- or slightly hypotensive doses,
      dilates both arterioles and large arteries and that this vasodilation is not
      homogeneous, affecting preferentially the brachial rather than the carotid
      vascular bed.

PMID- 7528311
TI  - Use of thiacetazone.

PMID- 7528312
TI  - Use of thiacetazone.

PMID- 7528310
TI  - Post-transfusion hepatitis: impact of non-A, non-B hepatitis surrogate tests.
      Canadian Post-Transfusion Hepatitis Prevention Study Group.
AB  - Canada has not introduced the non-A, non-B (NANB) surrogate marker tests
      (antibodies to hepatitis B core antigen and alanine aminotransferase) to screen
      donated blood. We evaluated the effect of NANB surrogate markers in reducing post
      transfusion hepatitis in a prospective randomised intervention study. From 1988
      to 1992, 4588 subjects were enrolled into two study groups that received
      allogeneic blood from which units positive for NANB surrogate markers were either
      withheld (n = 2311) or not withheld (n = 2277). We also assessed a simultaneous
      non-randomised cohort (n = 650) of subjects who received only syngeneic blood.
      All subjects were followed up for 6 months and assessed for the presence of post
      transfusion hepatitis due to hepatitis A, B, C, non ABC, Epstein-Barr virus (EBV)
      and cytomegalovirus (CMV). Withholding of blood containing NANB surrogate
      positive units reduced the overall post-transfusion hepatitis rate by 40% (p =
      0.065) and the hepatitis C rate by 70% (p = 0.05). Most of the benefit of NANB
      surrogate testing was due to reduced frequency of hepatitis C virus after
      transfusion before all donor blood was screened for anti-HCV. During this time
      the overall post-transfusion hepatitis rate per 1000 transfusion recipients was
      20.2 in the no-withhold group compared with 5.0 in the withhold group (p = 0.05),
      and the HCV hepatitis rate was 12.6 and 0 respectively (p = 0.06). After the
      introduction of HCV screening, the overall post-transfusion hepatitis rates were
      8.6 and 6.8 per 1000 (p = 0.55) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528314
TI  - Cortical response to exogenous visual stimulation during visual hallucinations.

PMID- 7528313
TI  - Use of thiacetazone.

PMID- 7528315
TI  - Characterization of tissue effects produced by the Prolase II lateral-firing
      neodymium:YAG laser fiber in the canine prostate.
AB  - The immediate and long term-effects of neodymium:YAG laser treatment with the
      ProLase II lateral-firing laser fiber in the canine prostate were evaluated.
      Fourteen male dogs, aged 3 years and older with established benign prostatic
      hyperplasia, underwent endoscopic ablation of the prostate using the ProLase II
      fiber. Subjects were treated at laser power settings of 60 watts (6 dogs), 75
      watts (4 dogs), or 90 watts (3 dogs), with a mean total energy delivery of 15,000
      joules. One dog underwent a sham procedure and served as a normal control.
      Prostates were examined grossly and histologically at 48 hours, 2 weeks, 4 weeks,
      or 8 weeks post-treatment. The cross-sectional diameter and volume of tissue
      ablation were measured in each prostate. Histological studies of the extent of
      thermal injury to the prostatic tissue and the course of healing of the prostatic
      urethra were performed. The mean cross-sectional diameter of tissue ablation was
      28.6 +/- 4.7 mm and mean volume of tissue ablation was 8.2 +/- 5.1 cc. No
      statistically significant difference in diameter or volume of tissue ablation was
      noted between varying power settings. Histological studies showed extensive
      tissue necrosis with hemorrhage and an acute inflammatory cell infiltrate at 48
      hours. By 8 weeks, total resolution of both necrosis and inflammatory changes
      with complete re-epithelialization of the prostatic urethra was observed.

PMID- 7528316
TI  - Effect of low-intensity argon laser irradiation on mitochondrial respiration.
AB  - We studied influences of low-intensity argon laser irradiation at various
      wavelengths on mitochondrial respiration in vitro. Isolated guinea pig liver
      mitochondria were suspended in an isotonic buffer solution (pH 7.4, 37 degrees
      C). The mitochondrial suspension was introduced into a constant temperature
      reaction chamber in which an irradiation fiber, a thermocouple, an oxygen
      electrode, and a stirrer were installed. Under respiratory conditions of state 4,
      state 3, and uncoupled respiration, mitochondrial oxygen consumption was measured
      during low-intensity argon laser irradiations at 351nm, 458 nm, and 514.5 nm. The
      351 nm and the 458 nm irradiations at 200 mW inhibited uncoupled respiration by
      19% and 11%, respectively, and the irradiation at 351 nm inhibited state 3
      respiration as well by 10%. In contrast, the 514.5 nm irradiation enhanced both
      state 3 and uncoupled respiration by 6-7%. Temperature reference experiments
      indicated that the thermal effect alone could not account for the effects of
      laser irradiation on mitochondrial oxygen consumption. These results suggest that
      the 351 nm and the 458 nm laser irradiation may injure the mitochondrial inner
      membrane, while the 514.5 nm laser irradiation may slightly promote the rate of
      ATP synthesis.

PMID- 7528318
TI  - Exercise-induced coronary angiogenesis: a review.
AB  - Numerous studies have examined the effects of exercise training on coronary
      angiogenesis. Although the conclusions drawn from these studies are sometimes
      conflicting, variabilities in training (magnitude, type and intensity), age and
      other factors need to be closely examined. Most studies on young animals indicate
      that capillary growth occurs providing that the training intensity is
      appropriate. Furthermore, there is evidence that growth of arteries and
      resistance vessels can occur as indicated by 1) direct measurements of vessels
      and 2) calculation of minimal coronary vascular resistance during
      pharmacologically induced vasodilation. Although the mechanism(s) underlying
      exercise-induced angiogenesis is unknown, mechanical events associated with
      increased flow and/or increased venous return, as well as resting bradycardia may
      serve to trigger growth factors involved in mitogenic, migratory, and tube
      formation of endothelial cells. In contrast, exercise training per se does not
      appear to enhance collateral vessel growth. However, there is evidence that
      collateral growth is accelerated with training in animals with coronary artery
      occlusion.

PMID- 7528319
TI  - Identification of adenylyl cyclases by amplification using degenerate primers.

PMID- 7528320
TI  - Infusion of guanine nucleotides through recording electrodes for studies on G
      protein regulation of ion currents and channels.

PMID- 7528317
TI  - Effects of exercise training on coronary circulation: introduction.
AB  - The purpose of this symposium was to evaluate the hypothesis that the beneficial
      effects of training are the result of training-induced adaptations in the
      coronary circulation. The approach is to review, summarize, and evaluate data
      concerning the effects of exercise training on the coronary circulation. Results
      indicate that aerobic exercise training induces an increase in both blood flow
      capacity and capillary exchange capacity. These functional changes are the result
      of two major types of adaptive responses: structural vascular adaptation and
      altered control of vascular resistance. Structural vascular adaptation occurs in
      response to exercise training in at least two forms: increases in the cross
      sectional area of the proximal coronary arteries, and angiogenesis. Training
      induced changes in coronary vascular control have been shown to include altered
      responses of the coronary circulation and isolated coronary arteries to
      vasoactive substances, changes in endothelium-mediated vasoregulation, and
      alterations in the cellular-molecular control of intracellular free Ca2+ in both
      endothelial and vascular smooth muscle cells isolated from coronary arteries of
      exercise trained animals. The potential impact of these training-induced
      adaptations on the coronary collateral circulation and atherosclerotic coronary
      disease are discussed.

PMID- 7528321
TI  - Injection of antisera into cells to study G-protein regulation of channel
      function.

PMID- 7528323
TI  - Reconstitution of receptor-regulated ion channels in isolated patch membrane.

PMID- 7528322
TI  - Whole-cell clamp analysis for G-protein regulation of channels.

PMID- 7528324
TI  - PITSLRE protein kinase activity is associated with apoptosis.
AB  - Minimal ectopic expression of a 58-kDa protein kinase (PITSLRE beta 1), distantly
      related to members of the cdc2 gene family, induces telophase delay, abnormal
      chromosome segregation, and decreased growth rates in Chinese hamster ovary
      cells. Here we show that this decrease in cell growth rate is due to apoptosis.
      Apoptosis is also induced by ectopic expression of an amino-terminal deletion
      mutant containing the catalytic and C-terminal domains of PITSLRE beta 1 but not
      by other mutants lacking histone H1 kinase activity or by other members of the
      cdc2 gene family. However, unlike the wild-type PITSLRE beta 1 over-expressors,
      ectopic expression of the N-terminal PITSLRE beta 1 mutant does not result in
      telophase delay or abnormal chromosome segregation. These results suggested that
      the function of this protein kinase could be linked to apoptotic signaling. To
      test this hypothesis, we examined levels of PITSLRE mRNA, steady-state protein,
      and enzyme activity in human T cells undergoing apoptosis after activation with
      the anti-Fas monoclonal antibody (MAb). All were substantially elevated shortly
      after Fas MAb treatment. In addition to new transcription and translation,
      proteolysis contributed to the increased steady-state levels of a novel 50-kDa
      PITSLRE protein, as suggested by the diminution of larger PITSLRE isoforms
      observed in the same cells. Indeed, treatment of the Fas-activated T cells with a
      serine protease inhibitor prevented apoptotic death and led to the accumulation
      of larger, less active PITSLRE kinase isoforms but not the enzymatically active
      50-kDa PITSLRE isoform. Finally, induction of apoptosis by glucocorticoids in the
      same cell line, as well as by Fas MAb treatment of another T-cell line, led to a
      similar induction of 50-kDa PITSLRE protein levels over time. These findings
      suggest that (i) PITSLRE kinase(s) may lie within apoptotic signaling pathway(s),
      (ii) serine protease activation may be an early event in Fas-activated apoptosis
      of human T cells, and (iii) some PITSLRE kinase isoforms may be targets of
      apoptotic proteases.

PMID- 7528325
TI  - Growth hormone rapidly activates rat serine protease inhibitor 2.1 gene
      transcription and induces a DNA-binding activity distinct from those of Stat1, 
      3, and -4.
AB  - Transcriptional regulation by growth hormone (GH) represents the culmination of
      signal transduction pathways that are initiated by the cell surface GH receptor
      and are targeted to the nucleus. Recent studies have demonstrated that the
      activated GH receptor can stimulate Stat1, a cytoplasmic transcription factor
      that becomes tyrosine phosphorylated and translocates to the nucleus, where it
      can interact with specific DNA sequences to modulate gene expression. GH also has
      been found to induce protein binding to a portion of the rat serine protease
      inhibitor (Spi) 2.1 gene promoter that is required for GH-induced transcription
      of Spi 2.1. Using GH-deficient hypophysectomized rats as a model, we show that GH
      treatment rapidly and potently induces both nuclear Spi 2.1 mRNA expression in
      the liver and specific nuclear protein binding to a 45-bp segment of the Spi 2.1
      gene promoter. A GH-inducible gel-shifted complex appears within 15 min of
      systemic hormone administration and can be inhibited by an antiphosphotyrosine
      monoclonal antibody but is not blocked by a polyclonal antiserum to Stat1, Stat3,
      or Stat4, even though the nucleotide sequence contains two gamma interferon
      activated sequence-like elements that could interact with STAT proteins. By
      Southwestern (DNA-protein) blot analysis, approximately 41- and 35-kDa GH
      inducible proteins were detected in hepatic nuclear extracts with the Spi 2.1 DNA
      probe. Thus, a GH-activated signaling pathway stimulates Spi 2.1 gene expression
      through a unique mechanism that does not appear to involve known members of the
      STAT family of transcription factors.

PMID- 7528326
TI  - Multiple molecular determinants for retrotransposition in a primer tRNA.
AB  - Retroviruses and long terminal repeat-containing retroelements use host-encoded
      tRNAs as primers for the synthesis of minus strong-stop DNA, the first
      intermediate in reverse transcription of the retroelement RNA. Usually, one or
      more specific tRNAs, including the primer, are selected and packaged within the
      virion. The reverse transcriptase (RT) interacts with the primer tRNA and
      initiates DNA synthesis. The structural and sequence features of primer tRNAs
      important for these specific interactions are poorly understood. We have
      developed a genetic assay in which mutants of tRNA(iMet), the primer for the Ty1
      retrotransposon of Saccharomyces cerevisiae, can be tested for the ability to
      serve as primers in the reverse transcription process. This system allows any
      tRNA mutant to be tested, regardless of its ability to function in the initiation
      of protein synthesis. We find that mutations in the T psi C loop and the acceptor
      stem regions of the tRNA(iMet) affect transposition most severely. Conversely,
      mutations in the anticodon region have only minimal effects on transposition.
      Further study of the acceptor stem and other mutants demonstrates that
      complementarity to the element primer binding site is a necessary but not
      sufficient requirement for effective tRNA priming. Finally, we have used
      interspecies hybrid initiator tRNA molecules to implicate nucleotides in the D
      arm as additional recognition determinants. Ty3 and Ty1, two very distantly
      related retrotransposons, require similar molecular determinants in this primer
      tRNA for transposition.

PMID- 7528327
TI  - Interaction of p72syk with the gamma and beta subunits of the high-affinity
      receptor for immunoglobulin E, Fc epsilon RI.
AB  - Activation of protein tyrosine kinases is one of the initial events following
      aggregation of the high-affinity receptor for immunoglobulin E (Fc epsilon RI) on
      RBL-2H3 cells, a model mast cell line. The protein tyrosine kinase p72syk (Syk),
      which contains two Src homology 2 (SH2) domains, is activated and associates with
      phosphorylated Fc epsilon RI subunits after receptor aggregation. In this report,
      we used Syk SH2 domains, expressed in tandem or individually, as fusion proteins
      to identify Syk-binding proteins in RBL-2H3 lysates. We show that the tandem Syk
      SH2 domains selectively associate with tyrosine-phosphorylated forms of the gamma
      and beta subunits of Fc epsilon RI. The isolated carboxy-proximal SH2 domain
      exhibited a significantly higher affinity for the Fc epsilon RI subunits than did
      the amino-proximal domain. When in tandem, the Syk SH2 domains showed enhanced
      binding to phosphorylated gamma and beta subunits. The conserved tyrosine-based
      activation motifs contained in the cytoplasmic domains of the gamma and beta
      subunits, characterized by two YXXL/I sequences in tandem, represent potential
      high-affinity binding sites for the dual SH2 domains of Syk. Peptide competition
      studies indicated that Syk exhibits a higher affinity for the phosphorylated
      tyrosine activation motif of the gamma subunit than for that of the beta subunit.
      In addition, we show that Syk is the major protein in RBL-2H3 cells that is
      affinity isolated with phosphorylated peptides corresponding to the
      phosphorylated gamma subunit motif. These data suggest that Syk associates with
      the gamma subunit of the high-affinity receptor for immunoglobulin E through an
      interaction between the tandem SH2 domains of SH2 domains of Syk and the
      phosphorylated tyrosine activation motif of the gamma subunit and that Syk may be
      the major signaling protein that binds to Fc epsilon RI tyrosine activation motif
      of the gamma subunit and that Syk may be the major signaling protein that binds
      to Dc epsilon tyrosine activation motifs in RBL-2H3 cells.

PMID- 7528330
TI  - Selection of efficient cleavage sites in target RNAs by using a ribozyme
      expression library.
AB  - Inactivation of gene expression by antisense mechanisms in general and by
      ribozymes in particular is a powerful technique for studying the function of a
      gene product. We have designed a strategy for expression of ribozymes, for
      selection of accessible cleavage sites in target RNAs, and for isolation of
      ribozymes from a library of random sequences flanking the unique sequence of a
      hammerhead. The expression cassette for ribozyme genes is based on adenovirus
      associated RNA. Alternatively, we used polymerase III or the T7 phage
      transcription machinery. The ribozyme sequences are positioned in the center of a
      stable stem-loop structure, allowing for a correctly folded ribozyme region
      within the expressed RNA. A library of ribozyme genes with random sequences of 13
      nucleotides on both sides of the hammerhead was generated. As an example,
      ribozymes which are specific for seven sites within the mRNA or nuclear RNA of
      human growth hormone were selected and identified. Sequencing of ribozyme genes
      reamplified from the library confirmed not only the predicted cleavage sites but
      also the presence of different ribozyme variants in the library. In a test of the
      ribozyme variants for repression of growth hormone synthesis in a cellular assay,
      the strongest effect (more than 99% inhibition) was found for the variant with
      the shortest stretch of complementarity (7 and 8 nucleotides on either side) to
      the target RNA. This basic strategy seems to be applicable to the selection of
      suitable target sites and to the isolation of corresponding ribozymes for any
      mRNA of interest.

PMID- 7528329
TI  - Alternatively spliced forms in the carboxy-terminal domain of the p53 protein
      regulate its ability to promote annealing of complementary single strands of
      nucleic acids.
AB  - The carboxy-terminal domain of the p53 protein comprising amino acid residues 311
      to 393 is able to promote the reassociation of single-stranded RNA or DNA into
      duplex hybrids. This domain is as efficient as the intact p53 protein in both the
      rate and the extent of the double-stranded product produced in this reaction.
      Both wild-type and mutant p53 proteins from cancerous cells carry out this
      reaction. The monoclonal antibody PAb421, which detects an epitope between
      residues 370 and 378, blocks the ability of p53 to reassociate single strands of
      RNA or DNA. Similarly, the alternative splice form of the murine p53 protein,
      which removes amino acid residues 364 to 390 and replaces them with 17 new amino
      acids, does not carry out the reassociation reaction with RNA or DNA. This is the
      first indication of functionally distinct properties of the alternative splice
      forms of p53. These results suggest that this splice alternative can regulate a
      p53-mediated reaction that may be related to the functions of this protein.

PMID- 7528331
TI  - A persistent RNA-DNA hybrid is formed during transcription at a phylogenetically
      conserved mitochondrial DNA sequence.
AB  - Critical features of the mitochondrial leading-strand DNA replication origin are
      conserved from Saccharomyces cerevisiae to humans. These include a promoter and a
      downstream GC-rich sequence block (CSBII) that encodes rGs within the primer RNA.
      During in vitro transcription at yeast mitochondrial replication origins, there
      is stable and persistent RNA-DNA hybrid formation that begins at the 5' end of
      the rG region. The short rG-dC sequence is the necessary and sufficient nucleic
      acid element for establishing stable hybrids, and the presence of rGs within the
      RNA strand of the RNA-DNA hybrid is required. The efficiency of hybrid formation
      depends on the length of RNA synthesized 5' to CSBII and the type of RNA
      polymerase employed. Once made, the RNA strand of an RNA-DNA hybrid can serve as
      an effective primer for mitochondrial DNA polymerase. These results reveal a new
      mechanism for persistent RNA-DNA hybrid formation and suggest a step in priming
      mitochondrial DNA replication that requires both mitochondrial RNA polymerase and
      an rG-dC sequence-specific event to form an extensive RNA-DNA hybrid.

PMID- 7528333
TI  - Predicting chemical carcinogenesis in rodents: the state of the art in light of a
      comparative exercise.
AB  - Within a recent comparative exercise, different approaches to the prediction of
      rodent carcinogenicity were challenged on a common set of chemicals bioassayed by
      the U.S. National Toxicology Program. The approaches were of very different
      natures. Some prediction systems looked for relationships between carcinogenicity
      and other, more quickly detectable biological events (activity-activity
      relationships, AAR). Some approaches tended to find structure-activity
      relationships (SAR). To give an objective evaluation of the results of the
      exercise, we have analyzed the rodent results and the predictions with the
      multivariate data analysis methods. The calculated performances varied according
      to the adopted carcinogenicity classification of the chemicals. When the four
      rodent results were summarized into a final + or - call, the Tennant approach
      (AAR method) showed the best performance (about 75% accuracy), whereas the best
      SAR systems had 60-65% accuracy. A common limitation of almost all the systems
      was the lack of specificity (too many false positives). Based on these results,
      better concordance was obtained when the input information was the very costly
      (and closer to the final endpoint) biological data, rather than the inexpensive
      (and farther from the endpoint) knowledge of the chemical structure. However,
      when the rodent results were summarized into a carcinogenicity classification
      that maintained, to some extent, the gradation intrinsic to the original
      experimental data, the performance of the AAR systems declined, and the SAR
      approaches showed a better performance. The difficulty in evaluating the various
      approaches was further complicated because of a fundamental difference in the
      approaches themselves: some approaches were 'pure' prediction methods (i.e. their
      predictions were rigorously based on information not inclusive of
      carcinogenicity); other approaches (e.g. Tennant, Weisburger) used 'mixed'
      information, inclusive of known carcinogenicity results from experiments
      performed before the NTP bioassays. As far as the SAR systems are concerned,
      their sets of predictions showed a fundamental similarity. This happened in spite
      of the extremely different procedures adopted to treat the chemical formula
      (initial information): very simple calculations (Benigni), intuition of the
      experts (Weisburger and Lijinsky), sophisticated computer programs (TOPKAT and
      CASE). The results of the Bakale Ke method, based on the experimental measurement
      of the chemical electrophilicity, and of the Salmonella typhimurium mutagenicity
      assay were similar to the patterns of predictions of the SAR methods.

PMID- 7528332
TI  - Evaluation of hydroquinone and chloral hydrate on the in vitro micronucleus test
      on isolated lymphocytes.
AB  - The cytochalasin B micronucleus test was performed in human peripheral lymphocyte
      cultures to assay the ability of hydroquinone and chloral hydrate to induce
      micronuclei, in the presence or absence of an exogenous metabolic activation
      system. Cultures and readings were performed in duplicate. No significant damage
      was found after treatment with chloral hydrate in this test system, whereas
      hydroquinone induced a clear positive response in one culture in the presence of
      metabolic activation during the G1 phase. Isolated lymphocytes used as a test
      system provide information about the test compound itself without interference by
      blood components. Comparison of the two readers' data showed few marked
      discrepancies in the number of micronuclei recorded in binucleated cells. Strict
      criteria for data analysis are therefore necessary to avoid intra-assay or
      operator variability.

PMID- 7528334
TI  - Comparative study on cytogenetic damage induced by homo-aza-steroidal esters in
      human lymphocytes.
AB  - The effect of P[N,N-bis(2-chloroethyl)amino]phenylacetate esters of 3 beta
      hydroxy-N-methyl-17 alpha-aza-D-homo-5 alpha-androstan-17-one (compound 3) and 3
      beta-hydroxy-17 alpha-aza-D-homo-5 alpha-androstane (compound 2) on sister
      chromatid exchange (SCE) frequencies and on human lymphocytes proliferation
      kinetics was studied. The results are compared with those of the P[N,N-bis(2
      chloroethyl)amino]phenylacetate esters of 3 beta-hydroxy-17 alpha-aza-D-homo-5
      alpha-androstan-17-one (compound 1). All compounds were found to be active in
      inducing markedly increased SCE rates and cell division delays. A correlation
      between potency for SCE induction, effectiveness in cell division delay and
      previously established antitumour activity of these compounds was observed.

PMID- 7528335
TI  - The kinetics of chromosome and DNA damage by streptonigrin in CHO cells.
AB  - CHO cells were pulse-treated for 20 min with increasing doses of streptonigrin
      (SN). First division cells analyzed 18 h after the end of treatment showed a
      combination of chromosome and chromatid aberrations with a typical dose-response
      curve. The frequency of SCEs in second division cells (24 h harvesting time) also
      exhibited a positive correlation with the SN dose. A high incidence of chromatid
      aberrations was detected in second and third division metaphases. This indicates
      that SN has a persistent clastogenic action that lasts for at least three cell
      cycles after the end of treatment. The kinetics of DNA damage and repair was
      studied by the alkaline unwinding and single cell gel methods. It was found that
      a pulse treatment with SN elicited a triphasic response characterized by repair
      damage-repair. It is proposed that SN forms stable complexes with the DNA. These
      complexes by a continuous cycling redox process would produce active oxygen
      species inducing direct damage to DNA.

PMID- 7528336
TI  - Cytogenetic adaptive response induced by pre-exposure in human lymphocytes and
      marrow cells of mice.
AB  - The frequencies of chromosomal aberrations both in human lymphocytes and in mouse
      marrow cells exposed to low-level radiation were higher than in their unexposed
      controls. However, the frequencies of chromosomal aberrations in two kinds of
      cells pre-exposed to low-level radiation induced by a subsequent high dose of X
      rays or gamma-rays were lower than those of the groups only exposed to high-level
      radiation. This implies that adaptive responses for cytogenetic indicators might
      be induced by pre-exposure to low-level radiation. The results also show the
      existence of possible variations between individual lymphocytes.

PMID- 7528337
TI  - Simplified and optimized kinetochore detection: cytogenetic marker for late-G2
      cells.
AB  - Cytogenetic detection of kinetochore proteins using the CREST antibody coupled
      with secondary antibodies labeled with different fluorescent probes has been
      optimized for several in vitro mammalian cell lines. This study investigated
      selected parameters including the influence of common fixatives (methanol,
      ethanol, methanol:acetic acid (3:1)), detergents (Triton-X100, Tween),
      fluorescent probes (CY3, BODIPY, FITC), washing protocols, and an antifading
      agent (paraphenylenediamine) on the detection of kinetochore proteins in control
      and X-ray (240 kVp)-irradiated cells. Utilizing an optimized fixation and
      staining protocol, a brilliant visualization of kinetochores in interphase cells
      was obtained in control as well as X-ray-irradiated interhase cells. Application
      of this improved kinetochore staining methodology readily permits discriminating
      cells containing either single or paired kinetochores, the latter of which are
      characteristic of late-G2 phase and prophase cells.

PMID- 7528338
TI  - Development of a sensitive in vitro method for identifying tumor promoters.
AB  - The identification and characterization of nongenotoxic carcinogens represents a
      significant challenge to toxicologists. In vitro methods for identifying tumor
      promoters with suitable sensitivity and specificity have been particularly
      elusive. Experiments are described which suggest that the human promyelocytic
      leukemia cell line HL-60 provides a sensitive indicator of promoter-induced
      changes to gene regulation and expression. As a result of differentiation these
      cells undergo a transition from a non-phagocytic suspension culture to an
      attached fibroblast-like culture which exhibits high phagocytic activity.
      Fluorescent latex particles were used as sensors to highlight the phagocytic
      phenotype and permitted the use of flow cytometry to automatically quantitate
      particle internalization. To evaluate specificity, HL-60 cells were treated with
      a series of phorbol esters covering a range of in vivo tumor promoting activity.
      Results indicate that this family of compounds induces HL-60 cells to
      differentiate in proportion to their in vivo promoting activity. To closely
      assess the sensitivity of the phagocytic endpoint, HL-60 cells were treated with
      picogram levels of 12-O-tetradecanoyl phorbol-13-acetate (TPA), whereupon
      increments as low as 50 pg of TPA per ml caused statistically significant
      increases in phagocytic activity. The experiments described herein suggest that
      in vitro differentiation of HL-60 cells may reflect the promoter-dependent
      modifications to gene expression that are observed in vivo during the promotion
      phase of carcinogenesis. The described method may represent a sensitive promoter
      screening assay which is both rapid and economical.

PMID- 7528339
TI  - An improved method of mouse liver micronucleus analysis: an application to age
      related genetic alteration and polyploidy study.
AB  - The performance of a micronucleus test in liver cells in vivo requires two
      laborious procedures: stimulation of hepatocytes to division and dissociation of
      liver tissue into a single-cell suspension. We propose the method of inhalation
      treatment of mice with carbon tetrachloride to induce cell proliferation and
      alkaline dissociation of previously fixed tissue. The micronucleus incidence and
      ploidy classes in terms of cytophotometric DNA content were determined in liver
      of mice of three age groups (around 2.5, 5.0 and 7.0 months old) after CCl4
      treatment or partial hepatectomy. The data obtained show that both methods give
      the same results. The fraction of micronucleated hepatocytes was 0.69% at the age
      of 2.5 months; it increased to 8.5% and then to 13.5% at 5.0 and 7.0 months
      respectively. Simultaneously, the ploidy classes changed both with the aging of
      the animal and after induced liver regeneration. The percentage distribution of
      micronucleated cells by ploidy class showed that cells carrying micronuclei were
      the higher ploidies rather than the population in general. Since polyploid cells
      contain multiple molecular targets for genetic damage, the micronucleation index
      per genome unit was estimated. Then the real rate of accumulation of both
      intrinsic endogenous (and probably the exogenously induced) preclastogenic
      genetic alterations in hepatocytes during the adulthood of mice was evaluated to
      be 0.03% per diploid genome per day. This seems to be the first description of
      the phenomenon of liver cell aging in terms of micronuclear aberrations.

PMID- 7528340
TI  - Distinct area distribution differences of micronuclei induced by clastogenic and
      aneuploidogenic chemicals in the bone marrow of the CD-1 mouse.
AB  - To distinguish between aneuploidogenic and clastogenic effects of test chemicals,
      area distributions of micronuclei (MN) in polychromatic erythrocytes (PE) from
      the mouse bone marrow were measured using an image analysis system.
      Triethylenemelamine (TEM), cytosine-beta-D-arabinofuranoside (ara-C), urethane
      (URT), cyclosphamide (CP), mitomycin C (MMC), colcemid (COL) and tubulazole C
      (TUB) were investigated for the induction of micronucleus area distributions. The
      area distribution of micronuclei of untreated mice was also determined.
      Reproducible small differences between the clastogens and the aneuploidogens were
      observed after measuring 1100-1200 micronuclei. A common feature of the
      distribution curves was a shoulder region in the same area range for all
      clastogens. The aneuploidogens COL and TUB showed a plateau (= wide peak) in this
      clastogenic shoulder region. For all clastogens, the integrated area of shoulder
      over a fitted function (shoulder strength) was evaluated. MMC and CP, thought to
      have some aneuploidogenic potential, showed an increased shoulder strength
      compared to TEM, ara-C and URT. The control area distribution had no similarities
      to the area distribution of either clastogens or aneuploidogens. In a further
      experiment, we attempted to correlate the size of micronuclei determined after
      treatment with the aneuploidogenic chemicals to the size of whole chromosomes.
      Micronuclei found by image analysis which bear chromosome-like structures (judged
      by light microscopy) were manually identified. This selection of micronuclei was
      area-distributed to determine the mean size of these micronuclei. None of the
      peaks and plateaus in the area distributions obtained with the aneuploidogenic
      chemicals could be attributed to the size of a chromosome.

PMID- 7528328
TI  - Activation of pp70/85 S6 kinases in interleukin-2-responsive lymphoid cells is
      mediated by phosphatidylinositol 3-kinase and inhibited by cyclic AMP.
AB  - Activation of phosphatidylinositol 3-kinase (PI3K) and activation of the 70/85
      kDa S6 protein kinases (alpha II and alpha I isoforms, referred to collectively
      as pp70S6k) have been independently linked to the regulation of cell
      proliferation. We demonstrate that these kinases lie on the same signalling
      pathway and that PI3K mediates the activation of pp70 by the cytokine interleukin
      2 (IL-2). We also show that the activation of pp70S6k can be blocked at different
      points along the signalling pathway by using specific inhibitors of T-cell
      proliferation. Inhibition of PI3K activity with structurally unrelated but highly
      specific PI3K inhibitors (wortmannin or LY294002) results in inhibition of IL-2
      dependent but not phorbol ester (conventional protein kinase C [cPKC])-dependent
      pp70S6k activation. The T-cell immunosuppressant rapamycin potently antagonizes
      IL-2-(PI3K)- and phorbol ester (cPKC)-mediated activation of pp70S6k. Thus,
      wortmannin and rapamycin antagonize IL-2-mediated activation of pp70S6k at
      distinct points along the PI3K-regulated signalling pathway, or rapamycin
      antagonizes another pathway required for pp70S6k activity. Agents that raise the
      concentration of intracellular cyclic AMP (cAMP) and activate cAMP-dependent
      protein kinase (PKA) also inhibit IL-2-dependent activation of pp70S6k. In this
      case, inhibition appears to occur at least two points in this signalling path.
      Like rapamycin, PKA appears to act downstream of cPKC-mediated pp70S6k
      activation, and like wortmannin, PKA antagonizes IL-2-dependent activation of
      PI3K. The results with rapamycin and wortmannin are of added interest since the
      yeast and mammalian rapamycin targets resemble PI3K in the catalytic domain.

PMID- 7528341
TI  - Analysis of micronucleated cells by flow cytometry. 4. Kinetic analysis of
      cytogenetic damage in blood.
AB  - Micronucleated cells (MN cells) generated spontaneously or by clastogen action
      accumulate in the peripheral blood of the mouse, and their presence reflects the
      level of chromosome damage. Traditionally, micronucleated cells have been scored
      by visual inspection. With the development of flow cytometry based scoring
      procedures, vast numbers of cells can be analyzed, making it possible to
      determine the change in the number of MN cells in the total peripheral blood
      pool. This report describes experiments whereby initial blood samples were
      obtained before dosing, providing mouse-specific controls for measuring
      subsequent changes in MN cells. Mice were then dosed with saline (solvent
      control), methyl methanesulfonate, cyclophosphamide or colchicine every 48 h and
      bled every 96 h for 12 days. For each blood sample, one million fixed
      erythrocytes (RBCs) were interrogated for the presence of micronuclei, and
      regression analysis was used to determine the rate of MN cell influx per day for
      each animal or sets of animals. To evaluate the effect of treatment on MN
      induction, the mean slopes of solvent and chemically treated animals were
      compared using t-tests. The results of these experiments indicate that the
      kinetics of MN induction continues near the background frequency for saline dosed
      mice, whereas clastogenic agents or spindle poisons cause a significant influx of
      MN events into the blood. The results suggest that some studies may benefit from
      a flow cytometry based analysis of multiple blood samples, especially when the
      number of mice is limited, or when a weak clastogen is being investigated.

PMID- 7528342
TI  - The effect of reducing the number of cells scored on the performance of the in
      vivo rat liver UDS assay.
AB  - The most labour-intensive feature of the in vivo rat liver UDS assay is the
      scoring of hepatocyte autoradiograms by microscope. Even with image analyser and
      computer equipment the scoring phase of a full study might require half of the
      technical effort applied. Practice recommended by guidelines has been to score 50
      cells/slide and two slides per animal. Now sufficient data have been accumulated,
      an evaluation was made to observe whether this procedure was necessary. An
      analysis of the accumulated UDS database in our laboratory was made to determine
      the sources of variability of mean net nuclear grain count, [N-C]. It was
      observed that the two largest components of variation in negative control animal
      mean [N-C] were between-day and interanimal variability. The contribution from
      sampling error during slide scoring was relatively small. Theoretical
      calculations showed that the greater sampling error derived from scoring 30
      rather than 50 cells/slide would result in only a marginal increase in total
      assay variation. To test this, 30 cells/slide were randomly selected from the 50
      cells scored originally in negative control animals in each of 18 studies over an
      18-month period. It was confirmed that reducing the number of cells had a
      negligible effect on the variation of negative control animal mean [N-C] values.
      Furthermore, analysis of data from 10 more studies confirmed that within-study
      variation would be essentially unaffected by scoring 30 cells/slide. The use of
      30 rather than 50 cells per slide (a total of 60 cells per animal) has therefore
      been adopted for all current studies and scoring procedures modified to avoid
      operator bias during the selection of a smaller number of cells.

PMID- 7528343
TI  - Automated metaphase finding: an assessment of the efficiency of the METAFER2
      system in a routine mutagenicity assay.
AB  - The efficiency of the automated metaphase finding system METAFER2 is assessed in
      a routine mutagenicity assay using an aneuploid rat liver cell line treated with
      various promutagens. Data sets generated by automated and manual selection of
      metaphases are compared. It is demonstrated that METAFER2 routinely allows an
      efficient automatic identification of metaphases not only in lymphocyte
      preparations, but also in preparations from mammalian cell lines with varying
      chromosome numbers. Although larger slide areas are required for automated
      compared to manual metaphase scanning, the automatic system is faster by a factor
      of about 5. The interactive visual elimination of metaphases of insufficient
      quality is an easy and fast procedure. METAFER2 allows an unbiased selection of
      metaphases irrespective of their appearance as homogeneously stained first or
      harlequin-stained second division cells. Random selection of metaphases is
      neither influenced by various structural chromosome changes nor by increased
      frequencies of sister-chromatid exchanges.

PMID- 7528344
TI  - Brief report: resistance to thyrotropin caused by mutations in the thyrotropin
      receptor gene.

PMID- 7528345
TI  - Isolation and identification of proteolipid proteins in jimpy mouse brain.
AB  - Proteolipids were isolated from 20 day old normal and jimpy mouse brain by
      extraction into chloroform-methanol (2:1, w/v), delipidated by size-exclusion
      HPLC, and analyzed by SDS-PAGE, Western blots, amino acid analyses, and N
      terminal sequencing. SDS-PAGE showed that a major proteolipid from jimpy mouse
      brain had an apparent molecular weight of approximately 23 kDa, intermediate to
      that of PLP and DM-20 from normal mouse brain. Western blots with 3 different
      antibodies which recognize residues 200-224, 116-150, and 270-276 respectively
      recognized immunoreactive material in normal and jimpy PLP. Since antibody
      reactive with 270-276 did not recognize jimpy PLP, an altered C-terminus of the
      jimpy protein is suggested. These results demonstrated that a PLP can be
      partially purified from jimpy mouse brain. Amino acid analyses failed to show the
      predicted increase in cysteinyl residues (predicted from cDNA) in jimpy PLP.
      However, when jimpy brain proteolipids were subjected to N-terminal sequencing,
      Gly, Leu, Leu, Gly the first four amino acids of PLP were detected. Thus, the
      partial purification of a proteolipid from jimpy mouse brain, whose
      characteristics (apparent molecular weight, immunoreactivity, N-terminal sequence
      and relative net charge) strongly suggested that PLP of altered size is present
      in jimpy mouse brain.

PMID- 7528346
TI  - Analysis of myelin proteolipid protein and F0 ATPase subunit 9 in normal and
      jimpy CNS.
AB  - Membrane fractions and chloroform-methanol (C-M) extracts of jimpy (jp) and
      normal CNS at 17-20 days were examined by immunoblot and sequence analysis to
      determine whether myelin proteolipid protein (FLP) or DM-20 could be detected in
      jp CNS. No reactivity was detected in jp samples with several PLP antibodies
      (Abs) except with one Ab to amino acids 109-128 of normal PLP. Proteins in the
      immunoreactive bands approximately 26 M(r) comigrating with PLP were sequenced
      for the first 10-12 residues. A sequence corresponding to PLP was found in normal
      CNS, as expected, but not in the band from jp CNS. Our results provide no
      evidence for an aberrant form of PLP in jp CNS at 17-20 days. This and other
      studies suggest that the abnormalities in jp brain are not due to toxicity of the
      mutant jp PLP/DM-20 proteins. Interestingly, a sequence identical to the amino
      terminus of the mature proton channel subunit 9 of mitochondrial F0 ATPase was
      detected in the immunoreactive bands approximately 26 M(r) in both normal and jp
      samples. This identification was supported by reactivity with an Ab to the F0
      subunit and by labeling with dicyclohexylcarbodiimide (DCCD). In contrast to PLP
      isolated from whole CNS, PLP isolated from myelin was devoid of F0 subunit 9
      based on sequence analysis and lack of reactivity with an Ab to the F0 subunit,
      yet still reacted with DCCD. This finding rules out the possibility that
      contaminating F0 ATPase gives rise to the DCCD binding exhibited by PLP and
      confirms the possibility that PLP has proton channel activity, as suggested by
      Lin and Lees (1,2).

PMID- 7528347
TI  - P0 phosphorylation in nerves from normal and diabetic rats: role of protein
      kinase C and turnover of phosphate groups.
AB  - The effects of phorbol ester and forskolin on the net phosphorylation and
      turnover of P0 phosphate groups was studied in normal and experimentally diabetic
      rats. In sciatic nerve segments isolated from normal rats and incubated with
      [32P]-inorganic phosphate, phosphorylation of the major peripheral myelin
      protein, P0, was increased 2-5 fold in a time and dose-dependent manner by
      phorbol 12,13 dibutyrate (PDB). This increase was blocked by the protein kinase
      inhibitors, H-7 and staurosporine. Both the basal and PDB-stimulated
      phosphorylation of P0 were significantly greater in segments of sciatic nerve
      from streptozotocin-induced diabetic rats. Prolonged exposure of nerve segments
      to PDB abolished the stimulated phosphorylation of P0 and immunoblots of nerve
      proteins revealed a decrease in the content of the protein kinase C alpha
      isoform. The adenylate cyclase activator, forskolin, had no effect on the PDB
      stimulated phosphorylation of P0 in normal nerve but decreased phosphorylation in
      diabetic nerve. To measure turnover of P0 phosphate groups, nerves were incubated
      with 32P and incorporated label was then chased in radioactivity-free medium for
      up to 4 hours. P0 from normal nerve prelabeled under basal conditions lost 25% of
      its radioactivity during this time. In contrast, nearly all of the additional
      phosphate groups prelabeled in the presence of PDB disappeared after 2 hours of
      chase. P0 phosphate groups from diabetic nerve displayed similar turnover
      kinetics. When forskolin was added to the chase medium, the turnover of P0
      phosphate moieties was accelerated in normal, but not in diabetic nerve.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7528348
TI  - Sulfate metabolism of rat P0 glycoprotein: some observations.
AB  - It has been known for some time that P0, the major intrinsic protein in PNS
      myelin, contains sulfate. The position of sulfate has been described for beef PNS
      myelin, but rat PNS myelin differs somewhat from that of the beef, therefore an
      investigation of the location of sulfate in rat P0 was undertaken. Weanling rat
      nerves were incubated with [3H] amino acid mixture and [35S]O4, and purified
      myelin was prepared, and the proteins separated on polyacrylamide gels. The bulk
      of the [35S]O4 was incorporated into P0, but smaller peaks of sulfate label were
      found in the higher molecular weight proteins. With tunicamycin in the incubation
      mixture, sulfate incorporation was inhibited. Incubation of the labeled myelin
      mixture with endo F or glycanase resulted in total loss of sulfate label on P0,
      therefore all of the [35S]O4 was incorporated into the oligosaccharide chain,
      with none on the polypeptide. Castanospermine and deoxymannojirimycin inhibited
      [35S]O4 incorporation into P0, but no inhibition was exerted by swainsonine.
      These results indicate that sulfate resides in the core of the oligosaccharide
      chain, with none in the terminal region. Such a structure would correlate with
      the lack of an HNK-1 epitope, absent in the rat, but found in P0 of many species.

PMID- 7528349
TI  - Tissue lipoproteins revisited: new proteolipid protein gene family members in
      elasmobranchs.
AB  - The proteolipids (PLPs) are abundant components of mammalian CNS myelin.
      Recombinant DNA methodologies have enabled us to search for evolutionary
      antecedents of PLP/DM20. Polymerase chain reactions of Torpedo and Squalus brain
      cDNA were performed with degenerate primers designed according to the mammalian
      PLP/DM20 sequence. Three DM20-related products (DM alpha, DM beta, and DM gamma)
      were amplified; no cDNAs containing the PLP-specific segment were found. Regions
      of the DM alpha and DM gamma are similar to the pore-forming segments of certain
      ligand-gated channels. In embryonic Squalus CNS, DM alpha and DM gamma appear to
      be co-expressed with P0. Antiserum raised against Torpedo DM alpha recognizes a
      protein in mouse CNS myelin, demonstrating that at least one of the newly
      recognized fish DMs is also in mammals. Our data, as well as that of other
      laboratories, supports the existence of a ubiquitously expressed proteolipid gene
      family.

PMID- 7528350
TI  - Transcriptional regulation of the rat PLP promoter in primary cultures of
      oligodendrocytes.
AB  - Proteolipid protein (PLP) is the major intrinsic membrane protein of CNS myelin
      and is expressed in oligodendrocytes as part of a coordinate program of myelin
      specific gene activation. In order to identify the DNA sequences and proteins
      involved in the regulation of PLP transcription, we have analyzed the 5' flanking
      sequences of the rat PLP gene by transient transfections into primary cultures of
      developing oligodendrocytes, the glial tumor line, C6, and L cells. High levels
      of expression of the CAT reporter gene in oligodendrocytes and C6 cells were
      obtained with constructs containing both 4270 and 225 bp of PLP promoter. A
      fusion construct containing 1061 bp of the PLP promoter, however, showed two-fold
      lower CAT expression. In addition, the activity of these promoter fusion
      constructs in oligodendrocytes was 2.5-4.6 higher than that observed in C6 cells,
      while very little expression was found in L cells. These data suggest that 225 bp
      of PLP promoter is sufficient for oligodendrocyte-specific regulation of PLP
      expression. Furthermore, both positive and negative elements within the PLP
      promoter are involved in this process. Finally, primary cultures of developing
      oligodendrocytes are a useful model system for the analysis of myelin-specific
      gene activation.

PMID- 7528351
TI  - Isolation and characterization of a cDNA encoding the zebra finch myelin
      proteolipid protein.
AB  - A cDNA was isolated from a zebra finch telencephalon cDNA library that encodes
      the myelin proteolipid protein. The clone was 2874 nucleotides long containing an
      open reading frame of 831 nucleotides that encoded a 277 amino acid myelin
      proteolipid protein. The 5'- and 3' untranslated regions were 112 and 1931
      nucleotides, respectively. In Northern blots the clone hybridized to 3 bands of
      3.5, 2.4 and 1.5 Kb in mouse brain RNA, but to only a single band of 3.0 kb in
      zebra finch brain RNA, suggesting the lack of alternative polyadenylation sites
      within the 3' untranslated region of the zebra finch PLP mRNAs. There was a small
      degree of homology between the zebra finch and chicken PLP 5' untranslated
      regions, but relatively little homology of the 5' untranslated regions of the
      zebra finch PLP cDNA clone with the homologous regions of PLP cDNAs of many
      mammalian species. Except for a small stretch of considerable homology, there was
      little overall homology with the 3' untranslated regions of mammalian PLP mRNAs.
      Approximately 10% (i.e. 28) of the amino acids in the zebra finch PLP differed
      from mammalian PLP, with most of these changes located within exon 3. There were
      16 amino acid changes between zebra finch and chicken, suggesting that greater
      sequence variation in PLP structure is tolerated among avian species than among
      mammalian species.

PMID- 7528352
TI  - Suppression of lymphocyte spontaneous proliferative response by proteolipid
      protein peptide in patients with HAM/TSP.
AB  - To understand the immune mechanism suggested in HTLV-I-associated myelopathy
      (HAM/TSP), we investigated T cell response to proteolipid protein (PLP). Because
      of high autologous proliferative response (APR) of peripheral blood mononuclear
      cells (PBMC) in culture, the lymphocyte proliferation assay was not useful in
      this disease. Unexpectedly, however, APR was profoundly (70-98%) suppressed in 6
      of 9 cases when PLP peptide 105-124 was added in the culture. PLP peptide 85-104
      or 145-159 also suppressed APR in a few cases. Time course study showed that the
      peptide-mediated suppression became apparent after day 4 in culture. The results
      can be interpreted as that suppressor cells recognizing the PLP peptides were
      present in the PBMC of HAM/TSP patients and suppressed the APR as the consequence
      of antigen specific response. This may indicate that a T cell response to certain
      PLP determinants is involved in the pathomechanism of HAM/TSP at least in part.
      Molecular mimicry between PLP and HTLV-I may account for the T cell sensitization
      to PLP in HAM/TSP.

PMID- 7528353
TI  - Contribution of transplantations to the understanding of the role of the PLP
      gene.
AB  - We present an overview of the results obtained in a cross-transplantation system
      using respectively controls, jimpy (jp), and shiverer mutant mice as donors and
      recipients. Homochronic transplantations (O days into O days) demonstrated that
      jp environment is non-toxic for non-jp cells and that, contrary to in vitro, jp
      oligodendrocytes phenotype cannot be modified by environmental factors at this
      age. Transplantations of embryonic fragments into the newborn brain demonstrated
      that in contrast to oligodendrocyte precursors contained in fragments of newborn
      tissue, jimpy embryonic stem cells are sensitive to environmental factors able to
      modulate the proportion of surviving oligodendrocytes. In addition, these series
      evidenced a disjunction between the surviving and the myelinating capacity of jp
      cells demonstrating a pleiotropic effect of the jp mutation on oligodendrocyte
      biology. Results are discussed with regards to the recent molecular biological
      finding on the role of the DM20/PLP gene.

PMID- 7528354
TI  - Minireview: autoimmune responses to myelin proteolipid protein.
AB  - The authors present a brief historical sketch of the development of our
      understanding of immune responses to myelin proteolipid protein (PLP) and the
      acceptance of PLP as a potent antigen in the induction of experimental allergic
      encephalomyelitis (EAE). The distinct characteristics of the PLP molecule that
      may contribute to complex immune responses to this protein are reviewed and these
      responses are compared with those to MBP, both in the pathology of EAE and at the
      level of the T cell. Recent evidence demonstrating differences between T cell
      responses to PLP and MBP is reviewed. Finally, the potential contribution of
      immune responses to PLP in human diseases, particularly multiple sclerosis (MS),
      that have been identified to date are then summarized.

PMID- 7528356
TI  - Membrane topology of PLP in CNS myelin: evaluation of models.
AB  - Three new models for proteolipid protein (PLP) topology in the myelin membrane
      have been proposed--the 4-helix N(in) and N(out) models of Popot (J. Membr. Biol.
      120:233-246), and the model of Weimbs and Stoffel (Biochemistry 31:12289-12296).
      Unlike the earlier models proposed by Laursen (Proc. Natl. Acad. Sci. USA 81:2912
      2916), Stoffel (Proc. Natl. Acad. Sci. USA. 81:5012-5016) and Hudson (J. Cell
      Biol. 109:717-727), the four hydrophobic clusters are all assigned as membrane
      spanning domains. The Popot-N(in) and Weimbs models, which are similar to the
      Laursen model, both assign the positively-charged domain, which is deleted from
      the DM20 transcript of PLP, to the cytoplasmic surface, while the Popot-N(out)
      model, similar to the Stoffel and Hudson models, assigns this sequence to the
      extracellular surface. Our calculations of membrane surface charge shows that the
      disposition of this basic domain greatly influences membrane interactions, by
      shifting the equilibrium myelin period to alkaline pH due to the electrostatic
      repulsion force at the extracellular apposition. In the Laursen, Popot-N(in) and
      Weimbs models, the onset of swelling was calculated to be at lower pH than in the
      Stoffel, Hudson and Popot-N(out) models, and lower than that observed
      experimentally with mouse optic nerve myelin. The absolute electron density
      profile of the myelin membrane that is derived from the x-ray diffraction
      patterns shows similar density levels at its cytoplasmic and extracellular
      surfaces. By contrast, the electron density profile calculated from a chemical
      model that includes lipids plus myelin basic protein (but not PLP) shows a higher
      density at the cytoplasmic than at the extracellular side.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7528358
TI  - Cognitive recovery in idiopathic normal pressure hydrocephalus: a prospective
      study.
AB  - Idiopathic normal-pressure hydrocephalus remains difficult to treat. Controversy
      exists as to whether or not shunting can really improve cognitive functions and
      whether quantified intracranial pressure monitoring (ICP-Mo) can predict
      postoperative improvement rates. Several studies have drawn attention to the lack
      of a prospective study concerning the surgical outcome of this condition. We have
      performed such a study on idiopathic normal-pressure hydrocephalus patients
      shunted on the basis of ICP-Mo when "high" waves (amplitude > 9 mm Hg) were
      present. Twenty-three patients underwent surgery. The preoperative and
      postoperative clinical states were assessed by a quantitative procedure blind to
      the ICP-Mo results. A clear postshunting improvement was seen in 96% of the
      patients at 1 year with a statistically significant correlation between high wave
      relative frequency and the grade of improvement (P < 0.05). At the same time,
      66.6% of shunted patients showed a significant improvement in cognitive
      functions. Complications of shunting were successfully managed without residual
      deficits in this series. We recommend the use of quantitative ICP-Mo as a
      criterion for surgery and to predict the improvement grade.

PMID- 7528357
TI  - Fine specificity of CD4+ T cell responses to the dominant encephalitogenic PLP
      139-151 peptide in SJL/J mice.
AB  - PLP 139-151(S) is the major encephalitogenic epitope of PLP in the SJL/J mouse.
      CD4+ T cells specific for PLP 139-151(S) induce a relapsing-remitting form of EAE
      which is similar to the human demyelinating disease MS in both clinical course
      and histopathology. We are interested in events involved in activation of
      autoreactive T cells and how to specifically regulate these immune response to
      both prevent and treat ongoing demyelinating disease. In the current study, we
      examined the effect of both amino acid substitutions and deletions in the native
      PLP 139-151(S) peptide to identify which residues are critical for immunogenicity
      and encephalitogenicity. Conservative and nonconservative substitutions at
      position 145 diminished or completely destroyed the encephalitogenic potential of
      the peptide without affecting the ability to recall a proliferative response in
      lymph node T cells primed with the native PLP 139-151(S) peptide indicating an
      interesting dichotomy between ability to induce T cell proliferation and ability
      to induce active clinical disease. In addition, tryptophan at position 144 was
      identified as a critical TCR contact site as a peptide containing an alanine for
      tryptophan at this position (A144) primed a unique population of T cells which
      did not cross react with the native PLP 139-151(S). In addition, A144 was unable
      to stimulate PLP 139-151(S)-specific T cells in vitro or to induce active
      relapsing EAE in vivo. The significance of these results to the potential
      development of new strategies for preventing and treating T cell-mediated
      autoimmune diseases is discussed.

PMID- 7528359
TI  - Detection and quantification of vascular endothelial growth factor/vascular
      permeability factor in brain tumor tissue and cyst fluid: the key to
      angiogenesis?
AB  - In primary malignant brain tumors increased vascularity and marked edema strongly
      suggest a possible role of the vascular endothelial growth factor/vascular
      permeability factor (VEGF/VPF). This was confirmed by earlier in situ
      hybridization studies, by analysis of the expression of the mitogen in different
      subsets of glioblastoma cells, and by the fact that the VEGF/VPF receptor flt-1
      (fms-like tyrosine kinase) is up-regulated in tumor cells in vivo. To assess and
      quantify the expression of the VEGF/VPF gene and of the receptor gene, 26
      surgical specimens of brain tumor tissue from 24 patients were analyzed. In most
      malignant gliomas, the expression level of the VEGF/VPF gene is elevated and can
      be increased up to 20- to 50-fold in comparison with low-grade tumors. Using
      polymerase chain reaction-based amplification, it could be shown that the
      messenger RNAs of three different VEGF/VPF forms are synthesized in tumor tissue
      samples. Northern blot studies revealed that in some samples a significant
      expression of the gene coding for placenta growth factor, a growth factor closely
      related to VEGF/VPF, was observed. In addition, using a radioreceptor assay it
      was possible to detect high VEGF/VPF-like activity in the cyst fluids of brain
      tumors, indicating the accumulation of the mitogen and permeability factor in
      brain tumor cysts. Further investigations revealed that astrocytoma and
      glioblastoma cells in culture express the VEGF/VPF gene and secrete the VEGF/VPF
      protein, whereas gene expression of the two known VEGF/VPF receptors, kinase
      insert domain-containing receptor and flt-1, could not be detected. These data
      support previous reports, which stated that VEGF/VPF acts as a paracrine growth
      and permeability factor in brain tumors and may contribute to tumor growth by
      initiating tumor angiogenesis.

PMID- 7528360
TI  - Renal effects of low dose aprotinin in pediatric cardiac surgery.
AB  - Two groups of 15 children aged from 15 days to 6 years, undergoing surgery on
      cardiopulmonary by-pass for congenital heart disease have been retrospectively
      analyzed. Group A received a low-dose aprotinin treatment (30,000 KIU/kg in the
      priming solution); group C (control group) did not receive any aprotinin. Groups
      were homogeneous for pathology, cardiopulmonary by-pass time, aortic cross
      clamping time, cyanotic/acyanotic patients ratio, temperature during
      cardiopulmonary bypass. A number of postoperative data were measured: activated
      clotting time was without any difference between aprotinin-treated and control
      patients; the same went for temperatures, urine output, intubation time, stay in
      Intensive Care Unit, coagulation tests, platelet counts, hematocrit, survival
      rate, and blood loss. Serum creatinine levels were significantly higher in group
      A than in group C both at the arrival in Intensive Care Unit (0.81 +/- 0.27 vs
      0.66 +/- 0.12, p = 0.032) and in the first postoperative day (1.01 +/- 0.5 vs
      0.72 +/- 0.19, p = 0.038). BUN was significantly higher in group A vs group C in
      the first postoperative day (43.6 +/- 21.1 vs 33.9 +/- 16.7, p = 0.043). We
      conclude that low-dose aprotinin did not reduce postoperative bleeding; we cannot
      exclude that higher dosages could be more effective, but the evidence of a
      moderate tubular function impairment suggests caution in using high-dose
      aprotinin in children.

PMID- 7528355
TI  - Peptide determinants of myelin proteolipid protein (PLP) in autoimmune
      demyelinating disease: a review.
AB  - This article reviews recent advances in understanding the role of myelin
      proteolipid protein (PLP) in autoimmune demyelination. It is drawn largely from
      work published within the last ten years and discusses the immunology of PLP in
      the historical context of what has been learned from extensive studies on the
      immune response to myelin basic protein (MBP). Despite the fact that PLP is the
      major protein constituent of mammalian myelin, its role in autoimmune
      demyelination has not been widely recognized. The lack of understanding about the
      immunology of PLP is a direct result of the biochemical characteristics of the
      protein. PLP is a highly hydrophobic membrane protein with limited aqueous
      solubility. The hydrophobicity of PLP has thwarted immunologic studies of the
      intact protein. Recent work has circumvented the technical obstacles of studying
      the intact protein by using soluble synthetic PLP peptides. This approach has
      rapidly resulted in a more definitive understanding of the immune response to
      PLP. Presently, the data indicate that: i) PLP is a major central nervous system
      (CNS) specific encephalitogen; ii) CD4+ T cell reactivity to discrete PLP peptide
      determinants can mediate the development of acute, chronic relapsing, and chronic
      progressive experimental autoimmune encephalomyelitis (EAE); and iii) T cell
      reactivity to multiple PLP determinants occurs in patients with multiple
      sclerosis (MS), the major human CNS demyelinating disease.

PMID- 7528361
TI  - Antiproteases and dialysis arthropathy.

PMID- 7528362
TI  - IgM antibodies to hepatitis C virus and haemodialysis patients.

PMID- 7528364
TI  - Acute renal failure and sepsis: therapeutic approaches.
AB  - Previous studies of experimental sepsis suggested that excessive systemic
      vasodilatation might be the stimulus to renal hypofiltration and fluid retention
      in sepsis. Successful therapy for this syndrome requires agents that either act
      to improve systemic haemodynamics without adverse renal effects, or that act
      directly on the kidney without impairing circulatory homeostasis. The plasma
      kallikrein-kinin system is a potent vasodilator pathway, activated by endotoxin.
      We studied the effect of aprotinin (Trasylol), which inhibits plasma kallikrein,
      in an ovine model of surgically-induced intra-abdominal sepsis. Given either as
      an early or late intervention, aprotinin was associated with increased mean
      arterial pressure and systemic vascular resistance, improved glomerular
      filtration rate, and increased urinary sodium excretion. In further studies,
      treatment with the thromboxane synthetase inhibitor, U63,557A (Upjohn), either
      before or after the surgical induction of peritonitis, was associated with
      increased glomerular filtration rate and sodium excretion, without any effect on
      systemic haemodynamics. Logical use of specific antagonists, based on an
      understanding of the pathophysiology of the septic ARF syndrome, is a desirable
      strategy.

PMID- 7528363
TI  - Nephrotoxicity of immunosuppressive drugs.
AB  - Acute and chronic nephrotoxicity frequently limits the therapeutic benefits of
      immunosuppressive therapy for transplant and autoimmune indications. The clinical
      aspects, pathophysiology, and relevant pharmacology of current and future
      immunosuppressive drugs are reviewed in this paper. Insights gained from
      experimental models of chronic nephrotoxicity associated with tubulointerstitial
      fibrosis are presented.

PMID- 7528366
TI  - Effect of inhibition of nitric oxide synthase in acute renal failure due to
      endotoxin shock in dogs.

PMID- 7528365
TI  - Role of nitric oxide in glycerol-induced acute renal failure in rats.
AB  - EDRF results from the metabolism of L-arginine. N-omega-nitro-L-arginine is a
      nitric oxide synthase inhibitor (L-arginine competitive inhibitor). Acute renal
      failure was induced by i.m glycerol (50%) 5 ml/kg bw. L-arginine: 3 mg/kg bw/min
      for 60 min before and 60 min after glycerol administration. L-arginine inhibitor
      (150 micrograms/kg bw/min for 120 min). Cin, Cpah and FENa% were measured
      immediately or 24 h after glycerol (mean of three periods of 20 min). A second
      series of similar experiments was done in dehydrated (16 h) rats with a high dose
      of glycerol (50% solution, 10 ml/kg bw). L-arginine ameliorates the severity of
      ARF immediately after glycerol administration and enhances the recovery of
      glycerol-induced ARF. The L-arginine inhibitor resulted in a more severe ARF.
      Urinary cGMP decreased significantly after glycerol administration. It is
      concluded that nitric oxide has an important pathogenetic role in the glycerol
      induced ARF.

PMID- 7528367
TI  - Toxic acute renal failure in the rat: effects of L-arginine and N-methyl-L
      arginine on renal function.
AB  - Nitric oxide (NO) is generated from L-arginine (Arg) by different isoforms of
      nitric oxide synthase (NOS) and plays a major role in maintaining the high basal
      renal blood flow. NO also is involved in the regulation of glomerular
      haemodynamics and contractility of mesangial cells. We examined the hypothesis
      that L-arginine-derived NO modifies toxic ARF in the rat. After a basal period
      uranyl nitrate (UN) was given intravenously as a bolus injection (25 mg/kg over 5
      min) to induce ARF. After the initiation phase of ARF (3 h) saline in the control
      group (C) and drugs in the experimental groups (I-III, each n = 8) were
      administered for 60 min. Group I, Arg (300 mg/kg); group II, MeArg (30 mg/kg);
      group III, Arg + MeArg (300 mg/kg, 30 mg/kg resp.). The experiments were
      continued for further 60 min following the infusion period. Glomerular filtration
      rate (GFR, inulin clearance) was reduced 3 h after UN to about 50% of normal
      values in groups I-III and control group (I, 0.52 +/- 0.06; II, 0.51 +/- 0.05;
      III, 0.49 +/- 0.05; C, 0.50 +/- 0.07 ml/min). After infusion of Arg GFR had
      significantly improved (0.64 +/- 0.07), but further declined after MeArg (0.46 +/
      0.06) in relation to control (0.47 +/- 0.07). This negative effect could be
      overcome by combined administration of Arg + MeArg (0.59 +/- 0.07). One hour
      after the infusion period these effects were even more pronounced (Arg, 0.71 +/-
      0.06; MeArg, 0.43 +/- 0.05; Arg + MeArg, 0.65 +/- 0.07; C, 0.46 +/- 0.05). We
      conclude that the L-arginine/NO pathway is involved in toxic ARF of the
      rat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528369
TI  - Effectiveness of combining maternal serum alpha-fetoprotein and hCG in a second
      trimester screening program for Down syndrome.

PMID- 7528371
TI  - Angiogenesis in malignant fibrous histiocytoma.
AB  - The significance of neovascularization for tumor growth and metastasis has
      recently been postulated for human cancers; increased microvessel density
      correlates with increased frequency of metastasis. In the present study,
      microvessel density was examined in 42 cases of malignant fibrous histiocytoma
      (MFH). Microvessels were defined as lumens surrounded by anti-factor-VIII-related
      antigen (FVIII-RA)-antibody-stained endothelium, and counted in a x 400 field.
      The number of microvessels varied from 4 to 79 (median 14.5). When cases were
      divided into groups with less than or greater than 20 microvessels, there were no
      prominent differences in age distribution, sex ratio, size of tumor, depth of
      tumor, and histologic subtypes between the two groups. The number of microvessels
      in 19 cases with and 22 cases without metastasis was 19.4 +/- 14.9 and 19.6 +/-
      17.4, respectively. Angiogenesis is apparently not a key factor in the formation
      of metastasis by MFH.

PMID- 7528370
TI  - Prevalence of hepatitis B, hepatitis C, and human immunodeficiency virus
      infection among women attending prenatal clinics in San Juan, Puerto Rico, from
      1989-1990.
AB  - OBJECTIVE: To evaluate the prevalence of hepatitis B virus (HBV), hepatitis C
      virus (HCV), and human immunodeficiency virus (HIV) among pregnant women in
      Puerto Rico. METHODS: An anonymous serosurvey was conducted in four prenatal
      clinics in San Juan, Puerto Rico, involving women presenting consecutively for
      their first prenatal visit. RESULTS: Nineteen of 997 pregnant women (1.9%, 95%
      confidence interval [CI] 1.2-3.0) tested positive for HCV antibody (anti-HCV),
      and eight (0.8%, 95% CI 0.4-1.6) were HIV seropositive. Of the 992 women for whom
      serum samples were tested for HBV markers, 91 (9.2%, 95% CI 7.5-11.2) had
      evidence of past or current HBV infection, and four (0.4%, 95% CI 0.1-1.1) were
      HBV carriers. The age-specific HBV prevalence ranged from 4.1% among women 15-19
      years old to 18.5% among those at least 30 years old (P < .001, chi 2 test for
      trend). Anti-HCV prevalence was also higher among women at least 30 years old
      compared to younger women (3.1 versus 1.9%; prevalence ratio 1.6, 95% CI 0.6
      4.9), although the difference was not statistically significant. Anti-HCV
      prevalence was higher among women with past or current HBV infection than among
      women who were not infected (7.7 versus 1.3%; prevalence ratio 5.8, 95% CI 2.3
      14.3). CONCLUSIONS: The prevalence of chronic HBV and HCV infection among
      pregnant women tested in San Juan, Puerto Rico, is comparable to that among
      pregnant women in the United States. The prevalence of HIV infection among
      pregnant women in San Juan is higher than among childbearing women in the United
      States.

PMID- 7528368
TI  - Are routine alpha-fetoprotein and acetylcholinesterase determinations still
      necessary at second-trimester amniocentesis? Impact of high-resolution
      ultrasonography.
AB  - OBJECTIVE: To audit routine measurement of alpha-fetoprotein (AFP) and
      acetylcholinesterase in amniotic fluid (AF) samples obtained at second-trimester
      amniocentesis. METHODS: We reviewed retrospectively 1737 consecutive AF specimens
      obtained for cytogenetic evaluation over a 4-year period and routinely assayed
      for AFP and acetylcholinesterase. In all instances, high-resolution
      ultrasonography was performed before amniocentesis. Details of pregnancy outcome
      of all cases with AF AFP levels greater than 2.0 multiples of the median and a
      positive or faint acetylcholinesterase band were obtained. RESULTS: There were 31
      abnormal results (1.8%, 1 of 56). Of these, 25 cases had elevated AF AFP and/or
      positive acetylcholinesterase. Ultrasonography correctly identified all 18
      fetuses with anomalies associated with abnormal levels of these biochemical
      markers, including open neural tube defects and/or anterior abdominal wall
      defects (17 cases) and fetal hydrops (one). In the remaining seven, no fetal
      anomalies were detected, and all neonates were structurally normal after birth.
      In addition, six pregnancies with faint acetylcholinesterase and normal AF AFP
      showed no fetal abnormalities at ultrasonographic examination and post-delivery.
      CONCLUSIONS: High-resolution ultrasonography was more accurate than AF
      biochemistry in the detection of congenital anomalies associated with elevated
      AFP levels and acetylcholinesterase in the AF. Routine measurement of these
      biochemical markers in AF samples obtained for cytogenetic analysis appears to
      have a very low yield and would therefore not be cost-effective in practices
      where high-resolution ultrasonography is performed before amniocentesis.

PMID- 7528372
TI  - Regulation of bone metabolism by the kallikrein-kinin system, the coagulation
      cascade, and the acute-phase reactants.
AB  - Inflammation-induced localized bone resorption in diseases such as marginal and
      apical periodontitis, rheumatoid arthritis, and osteomyelitis is due to
      activation and recruitment of osteoclasts by locally produced cytokines and
      inflammatory mediators. Thus several interleukins (1, 3, 4, 6, and 11), tumor
      necrosis factors (alpha, beta), colony-stimulating factors (M and GM), leukemia
      inhibitory factor, gamma-interferon, and transforming growth factor-beta have
      effects on bone resorption and bone formation in vivo and in vitro. The
      kallikrein-kinin system and the coagulation cascade are also activated in
      inflammation. We have found that peptides produced in the kallikrein-kinin system
      (bradykinin, kallidin) and thrombin, the end product in the coagulation cascade,
      can stimulate bone resorption in vitro. The stimulatory effect of bradykinin is
      linked both to B1 and B2 bradykinin receptors. Both kinins and thrombin stimulate
      prostaglandin biosynthesis in bone parallel with the bone resorptive effect. The
      stimulatory effect of bradykinin on bone resorption is completely lost when the
      prostaglandin response is abolished, whereas thrombin can stimulate bone
      resorption both via prostaglandin-dependent and independent mechanisms. In
      addition, bradykinin and thrombin act in concert with interleukin-1 to
      synergistically stimulate bone resorption and prostaglandin biosynthesis. We also
      have found that one of the acute-phase reactants, haptoglobin, can stimulate bone
      resorption in vitro, indicating the possibility of generalized bone loss in
      chronic inflammatory diseases. Moreover, haptoglobin synergistically potentiates
      bradykinin-induced and thrombin-induced prostanoid biosynthesis in osteoblasts.
      These observations indicate that the rate of bone resorption in inflammation
      induced bone loss may not be due to a single factor but to the concerted action
      of several local or systemic factors.

PMID- 7528373
TI  - Pharmacology of peripheral neuropeptide and inflammatory mediator release.
AB  - Research conducted in the last 10 years has increased our knowledge on pain
      mechanisms substantially. Although many local tissue mediators, including
      neuropeptides, are known to exert pro-inflammatory effects, comparatively little
      is known about the actual tissue levels of these inflammatory mediators and their
      pharmacologic regulation. This article describes two new methods, clinical
      microdialysis and superfusion of dental pulp, which provide data on the
      pharmacology of peripheral neuropeptide and inflammatory mediator release.
      Collectively, these methods provide a biochemically based approach toward
      determining the mechanisms and management of orofacial pain.

PMID- 7528374
TI  - Determination of the optimal aligned spacing between the Shine-Dalgarno sequence
      and the translation initiation codon of Escherichia coli mRNAs.
AB  - The prokaryotic mRNA ribosome binding site (RBS) usually contains part or all of
      a polypurine domain UAAGGAGGU known as the Shine-Dalgarno (SD) sequence found
      just 5' to the translation initiation codon. It is now clear that the SD sequence
      is important for identification of the translation initiation site on the mRNA by
      the ribosome, and that as a result, the spacing between the SD and the initiation
      codon strongly affects translational efficiency (1). It is not as clear, however,
      whether there is a unique optimal spacing. Complications involving the definition
      of the spacing as well as secondary structures have obscured matters. We thus
      undertook a systematic study by inserting two series of synthetic RBSs of varying
      spacing and SD sequence into a plasmid vector containing the chloramphenicol
      acetyltransferase gene. Care was taken not to introduce any secondary structure.
      Measurements of protein expression demonstrated an optimal aligned spacing of 5
      nt for both series. Since aligned spacing corresponds naturally to the spacing
      between the 3'-end of the 16S rRNA and the P-site, we conclude that there is a
      unique optimal aligned SD-AUG spacing in the absence of other complicating
      issues.

PMID- 7528376
TI  - Professional development. Wound care: knowledge for practice (continuing
      education credit).

PMID- 7528375
TI  - Anti-human immunodeficiency virus type 1 activity of phosphorothioate analogs of
      oligodeoxynucleotides: penetration and localization of oligodeoxynucleotides in
      HIV-1-infected MOLT-4 cells.
AB  - Phosphorothioate antisense oligodeoxynucleotide against HIV-1 rev (S-ODN-rev)
      inhibits virus-induced cytopathic effects (CPE) in acute infection and inhibits
      the expression of HIV-1 core protein, p24, in chronically infected cells in
      vitro. HIV-1 reverse transcriptase activity was not affected by S-ODN-rev at the
      high concentrations of 5-25 microM, which were 250-1250 times higher than the
      concentration required to achieve 100% HIV-1-induced CPE inhibition. [32P]
      labeled S-ODN-rev was rapidly uptaken by MOLT-4 cells, whereas [32P]-SO-ODN-rev
      and [32P]-O-ODN-rev were not. In the observation of FITC-S-ODN-rev-treated MOLT-4
      cells by a confocal laser scanning microscope, diffuse fluorescence was
      apparently observed in the cytoplasm. Interestingly, fluorescence signals were
      accumulated in the nuclear region of chronically infected MOLT-4/HIV-1 cells 60
      min after incubation. FITC-labeled homooligomer, FITC-S-dC20 and FIT-C-S-dT20,
      also accumulated in the nucleus of MOLT-4/HIV-1 cells, but weak fluorescence was
      observed on the cell membrane and in the cytoplasm of the FITC-S-random treated
      MOLT-4/HIV-1 and MOLT-4 cells.

PMID- 7528379
TI  - Dietary copper deficiency increases the mast cell population of the rat.
AB  - Mast cell-released histamine has been implicated in the enhanced acute
      inflammatory response of copper-deficient rats. The present study examined
      possible changes in the copper-deficient mast cell which may account for
      increased macromolecular leakage and edema formation. Mast cell populations were
      determined in the cremaster muscle of copper-adequate and copper-deficient rats.
      Total histamine content, unstimulated histamine release and concentration
      dependent histamine release with the mast cell secretagogue compound 48/80 were
      also determined in isolated peritoneal mast cells. A significantly higher number
      of mast cells were found in the cremaster muscle of the copper-deficient rats (78
      +/- 7 cells/5 microns section) than in the copper-adequate controls (51 +/- 4).
      Total histamine content per cell as well as unstimulated and stimulated release
      of the inflammatory mediator per cell were not different between the groups. The
      results suggest that dietary copper deficiency increases the mast cell population
      but does not alter the mast cell histamine content or sensitivity to
      degranulation in the rat. This increase in the number of mast cells may be a
      mechanism by which acute inflammation is enhanced in copper deficiency.

PMID- 7528378
TI  - O,O,S-trimethyl phosphorothioate increases Ca2+ independent nitric oxide synthase
      activity in the lung but decreases Ca2+/calmodulin dependent type in the
      cerebellum in Fischer 344 rats.
AB  - In the present study, we investigated the possible role of nitric oxide synthase
      in lung injury using female Fischer 344 rats as a model animal and O,O,S
      trimethyl phosphorothioate as an example of lung toxicants. One form of nitric
      oxide synthase, Ca2+/calmodulin dependent type, decreased monotonously in a dose
      dependent manner in the cerebellum. In contrast, O,O,S-trimethyl phosphorothioate
      increased activities of Ca2+ independent nitric oxide synthase in the lung in a
      dose-associated manner from 5 mg/kg to 15 mg/kg, but decreased at 30 mg/kg. Lung
      toxicity of O,O,S-trimethyl phosphorothioate, however, as judged both by
      functional impairments (PaCO2 and [HCO3-]) and histopathological changes,
      increased sharply at 30 mg/kg. We thus tested the hypothesis that a potent nitric
      oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester, may modify lung
      injury induced by O,O,S-trimethyl phosphorothioate. Treatment with NG-nitro-L
      arginine-methyl ester at 20 mg/kg/day aggravated lung injury induced by O,O,S
      trimethyl phosphorothioate: Pulmonary oedema and bleeding occurred, leading to an
      increase in mortalities at 15 mg/kg of O,O,S-trimethyl phosphorothioate, at which
      level it did not induce such changes as when dosed alone. These findings indicate
      that nitric oxide synthase in the lung might play a protective role in lung
      injury.

PMID- 7528380
TI  - Benign prostatic hyperplasia. Recent progress in clinical research and practice.
      Proceedings of the 2nd International Congress of the Dutch Urological
      Association. Amsterdam, November 4-6, 1993.

PMID- 7528377
TI  - Making sense of maternal serum screening.
AB  - Maternal serum screening (the 'triple test') is used to screen for Down's
      syndrome in pregnancy. This paper discusses the test and implications for
      practitioners.

PMID- 7528381
TI  - A critique of scoring systems.

PMID- 7528383
TI  - The principles and clinical application of advanced urodynamic analysis for BPH.

PMID- 7528382
TI  - Correlation between urinary flow rate, voided volume, and patient age in a
      community-based population.
AB  - This investigation is unique in that is the first study to use a large number of
      randomly chosen men from the community to establish the relationship between: 1)
      urinary flow rate and voided volume, 2) urinary flow rate and patient age, 3)
      voided volume and patient age, and 4) the time to achieve peak urinary flow rate
      and patient age. The results clearly indicate that both the peak and mean urinary
      flow rate decreases with advancing age. The voided volume also diminishes with
      increasing age. The time required to achieve the peak urinary flow rate, however,
      appears to be independent of the patient's age. Irrespective of age,
      approximately 9 seconds are required to achieve the maximum urinary flow rate.
      Because the urinary flow rate is dependent upon both the quantity of urine voided
      and the patient's age, it is necessary to account for the influence of both
      parameters when establishing the "normal range" for peak urinary flow rate. To
      this end, nomograms estimating the peak urinary flow rate percentile as a
      function of voided volume and patient age have been generated and are included in
      this report. These nomograms, based on a large, randomly selected population,
      should make peak urinary flow rate a more reliable diagnostic modality for
      assessing bladder outlet obstruction. They also should be most useful to the
      practicing clinician when interpreting the results of a peak urinary flow rate
      determination for a patient presenting with symptoms of prostatism.

PMID- 7528384
TI  - Urodynamic assessment of obstruction prior to and after surgery or medical
      treatment for BPH.

PMID- 7528385
TI  - The assessment of medical treatment for benign prostatic hyperplasia (BPH).

PMID- 7528386
TI  - Medical treatment of benign prostatic hyperplasia: the effect of surgical or
      medical castration.

PMID- 7528387
TI  - Benign prostatic hyperplasia: dihydrotestosterone and 5 alpha-reductase
      inhibition therapy.

PMID- 7528388
TI  - Clinical results with finasteride.

PMID- 7528389
TI  - The function and the role of aromatase inhibitors in the treatment of BPH.

PMID- 7528390
TI  - Anatomy of the prostate: insight into benign prostatic hyperplasia anatomy and
      pathogenesis.

PMID- 7528393
TI  - Effects of obstruction on bladder contractile proteins.
AB  - In an animal model of obstruction, increasing load induces significant smooth
      muscle hypertrophy which is associated with a down-regulation of myosin heavy
      chain expression. This undoubtedly contributes to the decreased smooth muscle
      contractility seen in this model. Moreover, obstruction-induced hypertrophy leads
      to the development of a dedifferentiated smooth muscle phenotype. Similar
      alterations are seen in atherosclerotic vessels and other pathologic smooth
      muscle systems. In these systems, dedifferentiation is also associated with
      significant alterations in extracellular matrix expression. It seems likely that
      obstruction in the bladder induces dedifferentiation of the smooth muscle cell
      which alters contractility as well as extracellular matrix expression, leading to
      altered bladder performance and decreased compliance.

PMID- 7528394
TI  - Prostatic alpha adrenoceptors.

PMID- 7528395
TI  - The role of alpha blockers in BPH.

PMID- 7528392
TI  - The pathophysiology of clinical BPH.

PMID- 7528396
TI  - Clinical results with alpha-blockers in patients with symptomatic benign
      prostatic hyperplasia.

PMID- 7528397
TI  - Analysis of watchful waiting studies.

PMID- 7528398
TI  - New insights into the epidemiology and natural history of benign prostatic
      hyperplasia.
AB  - Benign Prostatic Hyperplasia (BPH) has undoubtedly been an important cause of the
      urinary difficulties observed in elderly men for many centuries although the
      condition was only recognised as such during the last century. Benign Prostatic
      Hyperplasia is a very common condition (88 per cent of autopsy specimens in men
      aged over 80 have histological BPH) and the cause of the commonest surgical
      procedure in elderly men (three men in ten ultimately may require surgery for
      this condition). A common cause of death in elderly men just 20-30 years ago,
      improved medical care has seen dramatic declines in this aspect of BPH and today
      treatment choices in BPH are largely determined by considerations of quality-of
      life. Despite such a common occurrence, little is known with any certainty about
      the epidemiology of BPH. The incidence, even the population prevalence, is
      difficult to determine for a variety of reasons associated with difficulties
      surrounding the diagnosis of BPH and the identification of a source population to
      provide a denominator to calculate rates. Knowledge of risk factors is sparse:
      analytical epidemiologic studies of BPH are difficult to conduct. Case-control
      studies, the most commonly employed design in epidemiology, are problematic in
      that a control group may be difficult to define in view of the likelihood that a
      large proportion of these may have undiagnosed BPH. Against this background,
      knowledge of the prostate in the general population was sought in an
      international survey and found to be poor: although most men are aware of its
      existence, very few could correctly identify the function of the gland. Men
      tended to discuss urination problems with their doctors not when a symptom
      develops but when that symptom becomes bothersome. A 10-fold variation in
      frequency of rectal examination was identified between men in Germany and Italy
      which could not be explained by potential confounding variables. Given the large
      increases in the number of males reaching older ages, it is clear that BPH will
      continue to have substantial and increasing influence in terms of morbidity,
      mortality and health costs. Before the end of the present century, the life
      expectancy of a male at birth will exceed 80 years in many of the developed
      countries. Put put another way, one man in every two born can expect to reach an
      at which he has an 88 per cent chance of having a prostate with morphological
      BPH. Clearly, the need for high quality epidemiological information and
      consequent increased prospects for prevention is obvious.

PMID- 7528391
TI  - Endocrine therapies for BPH: scientific rationale, clinical results, and patient
      selection.
AB  - In 1993, medical therapy for BPH is a reality. Androgen deprivation therapy (LHRH
      agonists, antiandrogens, and 5 alpha-reductase inhibitors) has been shown to be
      effective by reducing the static component of BPH. Of these agents, the 5 alpha
      reductase inhibitors have the greatest promise because of their low toxicity
      profile. Aromatase inhibitors, which function via a different mechanism, however,
      have not been demonstrated, as monotherapy, to be effective in the treatment of
      symptomatic BPH. It is still theoretically possible that aromatase inhibitors
      could have a role in the management of prostatism if they are utilized in
      conjunction with an antiandrogen or 5 alpha-reductase inhibitor. Although the
      early results for this endocrine therapies are encouraging, several issues
      relating to medical treatment remain unanswered. Not everyone with significant
      prostatism will respond to androgen deprivation therapy. How does the physician
      identify pre-treatment the patient most likely to achieve a significant
      improvement in voiding function with 5 alpha-reductase inhibitor therapy? At the
      present time, there is no method--based on symptoms, DRE findings, serum hormone
      and PSA levels, or histopathologic criteria--for recognizing the ideal patient
      for androgen deprivation therapy. Without question, it is a subjective decision.
      As a result, the benefits and risks of these medical approaches as well as those
      of the minimally invasive and surgical therapies must be discussed with the
      patient so that he can participate in the management decision. In this manner,
      the expectations and needs of the patient will be best served.

PMID- 7528400
TI  - The role of the general practitioner in the diagnosis and treatment of benign
      prostatic hyperplasia (BPH).

PMID- 7528401
TI  - The pathogenesis of BPH: role of hormones.

PMID- 7528402
TI  - BPH: when to rule out carcinoma of the prostate.
AB  - With the inevitable increase in non-surgical management of the many thousands of
      patients with assumed benign prostatic enlargement, the issue of undiagnosed
      prostatic cancer needs to be addressed. Currently our knowledge is incomplete in
      many areas, especially that pertaining to the outcome of therapy of incidentally
      discovered prostate cancers. Nonetheless common sense dictates that all patients
      presenting with clinical BPH should undergo DRE and those with palpable
      induration or asymmetry should be biopsied in the knowledge that around a third
      will prove positive. Ideally all patients with clinical BPH should also have a
      PSA determination, however, the result should be interpreted with care, taking
      into account the age and estimated life-expectancy of the patient. Patients
      younger than 75 with a PSA > 10 ng/ml should probably be biopsied routinely-
      around half will have cancer. Patients with PSA values between 4 and 10 (around
      50% of cases of BPH) may legitimately be carefully observed for a period. Biopsy
      should be performed if an increase of > 20% in the PSA occurs during the year of
      follow-up especially in younger patients. Evidence is mounting that TRUS has
      serious deficiencies in identifying prostate cancers, nonetheless it does provide
      the most effective means of accomplishing transrectal prostatic biopsy. Further
      studies are required to critically evaluate the competing claims for improved
      diagnostic accuracy of PSAD, PSAV and age-adjusted PSA, the last of which does
      have the advantage of practicability.

PMID- 7528399
TI  - Medical management of benign prostatic hyperplasia other than with hormones or
      alpha blockers.

PMID- 7528403
TI  - Benign prostatic hyperplasia: the incidence of prostatectomy within and without
      Europe.

PMID- 7528404
TI  - The indications for surgical treatment of BPH.

PMID- 7528405
TI  - Selection of the surgical procedure for management of benign prostatic
      hyperplasia.
AB  - The standard method of surgically treating obstructing benign prostatic
      hyperplasia is transurethral resection of the prostate. It is the gold standard
      by which other therapeutic modalities, medical and surgical, should be measured.
      In those patients with larger prostate, open prostatectomy is the procedure of
      choice. Transurethral incision of the prostate has been under-utilized and would
      be useful in the majority of patients. The procedure is best used in patients who
      have glands under 30 grams and preferably around 20 grams in size. Therefore, in
      a given patient, the surgical procedure will be dependent upon the patient's
      general condition, the anatomy and size of his prostate, and the surgeon's skill
      and experience. Newer less invasive procedures are currently under evaluation and
      must be compared to transurethral prostatectomy, so that we can determine their
      possible role in the armamentarium of the urologist. Prospective randomized
      studies, comparing these new modalities to TUR-P, are needed, particularly with
      long-term outcome data.

PMID- 7528408
TI  - Video-TUR: raising the golden standard.

PMID- 7528406
TI  - The morbidity and mortality of BPH surgery.

PMID- 7528407
TI  - Fluid absorption and endotoxinemia during transurethral prostatic resection.

PMID- 7528409
TI  - Economics of BPH: measuring the intangible costs.

PMID- 7528411
TI  - The rational basis for thermotherapy of BPH.

PMID- 7528410
TI  - Some socio-economic issues surrounding prostatectomy: the US experience.

PMID- 7528413
TI  - Hyperthermia: a randomized prospective study applying hyperthermia or a sham
      procedure in obstructive benign hyperplasia of the prostate.

PMID- 7528412
TI  - The role of growth factors in the pathogenesis of BPH.

PMID- 7528414
TI  - The efficacy of microwave induced hyperthermia in the treatment of BPH: the Paris
      public hospitals' experience.

PMID- 7528415
TI  - Transurethral microwave thermotherapy versus transurethral resection for BPH.

PMID- 7528416
TI  - High intensity focused ultrasound treatment of human BPH.

PMID- 7528417
TI  - Thermal ablation of BPH with transrectal high-intensity focused ultrasound.

PMID- 7528418
TI  - Transurethral needle ablation (TUNA): histopathological, radiological and
      clinical studies of a new office procedure for treatment of benign prostatic
      hyperplasia.
AB  - Many attempts have been made to develop a method for treating benign prostatic
      hyperplasia (BPH) that is minimally invasive, efficacious, and low cost. The
      transurethral needle ablation (TUNA) device has recently been developed to treat
      BPH by selectively ablating hyperplastic prostatic tissue. A special catheter
      incorporates needles that deliver low-level radiofrequency power directly to a
      very localized area of the prostate. The needles have adjustable shields to
      protect the urethra if desired or necessary. It is positioned via transrectal
      ultrasound or direct vision. A pilot study was performed in patients to evaluate
      TUNA feasibility via histopathological measurement of the size of the thermal
      lesion and TUNA safety. Fifty patients have been treated, twenty-five patients
      were treated using TUNA prior to scheduled retropubic prostatectomy. The surgical
      prostatic specimens were recovered from 1 day to 1 month after TUNA, were step
      sectioned, and examined histologically. Patients were 69 years old on average
      with a prostate weight varying from 14 to 88 g. The TUNA procedure averaged 30
      minutes, 4 lesion treatments per prostate, and 4-15 W of power applied for 3 to 5
      minutes. Proximal lesion temperature was about 40-70 degrees C with central
      lesion temperatures of about 110 degrees C. Urethral temperature averaged 37-42
      degrees C and rectal temperature remained unchanged. Macroscopic examination of
      the specimens demonstrated localized lesions averaging 12 x 7 mm for 3 mins. and
      10 x 17 for 5 mins. treatment. Microscopic examination showed larger lesions of
      extensive coagulative necrosis up to 35 x 15 mm. Specific immunohistochemical
      staining showed destruction of all tissue components. Preservation of the urethra
      and capsule integrity were noted. Magnetic resonance imaging performed in vivo
      and ex vivo showed lesions in the prostate corresponding to the recovered
      surgical specimen. All patients were treated without anesthesia and tolerated the
      procedure well. Of the 9 patients treated for chronic retention, 6 recovered
      voiding within 48 hours. Three month follow-up in 11 patients showed significant
      improvement in both objective and subjective parameters. Because of good lesion
      localization and maintenance of a normal rectal temperature TUNA appears to be
      safe. The feasibility of its widespread use was shown by the creation and
      sustainability of adequately sized lesions and good tolerance as an outpatient
      treatment. Ongoing clinical studies are evaluating the sustained efficacy of the
      procedure.

PMID- 7528419
TI  - Thermotherapy and Hyperthermia Workshop.

PMID- 7528420
TI  - Laser dosimetry studies in a canine prostate model.

PMID- 7528421
TI  - Benign prostatic hyperplasia: morphometric studies in relation to the hormone
      sensitivity of stromal tissue.

PMID- 7528422
TI  - Optimization of laser prostatectomy.
AB  - A recent development in the treatment of Benign Prostatic Hyperplasia (BPH) is
      the use of a side firing fiber device coupled with a Nd:YAG laser. In this study,
      a numerical and an in-vitro model were developed to calculate and visualize the
      temperature distribution and the associated tissue necrosis due to irradiation of
      the prostate with Nd:YAG laser light. Different irradiation modalities were
      included: a static beam, with the irradiating fiber remaining at one place and a
      moving beam, with the fiber scanning over the surface at different speeds. Also
      blood vessels were incorporated in the model and showed to have major influence
      on the resulting tissue necrosis.

PMID- 7528424
TI  - Transurethral ultrasound guided laser induced prostatectomy (TULIP): U.S.
      Cooperative Study and University of Bochum results.

PMID- 7528423
TI  - Interstitial laser coagulation of the prostate: experiences in the treatment of
      benign prostatic hyperplasia.

PMID- 7528425
TI  - Laser treatment of benign prostatic hyperplasia (BPH) workshop.

PMID- 7528427
TI  - The UroLume endoprosthesis: a summary of the European and North American
      experience.
AB  - The UroLume Endoprosthesis, although originally developed for endovascular use,
      has received much interest in recent years for maintaining patency of the male
      urethra. It is a permanent, flexible, self-expanding device that becomes covered
      with epithelium and incorporated into the urethral wall. It is being investigated
      as an effective treatment for recurrent bulbar urethral strictures, BPH, and
      detrusor-external sphincter dyssynergia. Based on preliminary results, difficult
      strictures of nontraumatic origin can be treated very effectively with this
      endoprosthesis; recurrence is a rare event, even with long-term follow-up. This
      endoprosthesis maintains a large intraluminal diameter in the bulbar urethra,
      which allows for subsequent catheterization, cystoscopy, and ureteroscopy once
      epithelialization has occurred. Its placement in the bulbar urethra is
      straightforward and fast; significant complications are virtually nonexistent.
      Symptomatic patients with an obstructing prostate gland, in which the prostatic
      urethra is at least 2.5 cm in length and there is no significant median lobe, can
      be treated successfully with the UroLume Endoprosthesis. Improvements in
      obstructive symptoms and peak urinary flow rate approach those of TURP. Many
      patients, however, do experience irritative voiding symptoms in the immediate
      postoperative period. If additional studies--that have the proper control arm, a
      large number of patients, and long-term follow-up--demonstrate this
      endoprosthesis to be an effective treatment of BPH, its advantages are numerous.
      They include: 1) placement with the patient under regional anesthesia or with a
      prostatic block and intravenously administered sedative only; 2) short operating
      time (10-15 minutes or less) once the procedure is learned; 3) minimal to no
      intraoperative and postoperative hemorrhage; 4) no indwelling urethral catheter
      postoperatively; 5) dismissal on the same day or the following morning; 6)
      minimal convalescence; 7) no effect on the serum prostate-specific antigen (PSA)
      concentration; and 8) a one-time treatment performed by the practicing urologist.
      Preliminary studies evaluating the UroLume Endoprosthesis as a treatment for
      detrusor-external sphincter dyssynergia also have yielded positive results. It is
      effective in lowering intravesical voiding pressures, allowing for complete
      bladder emptying, preventing dilatation of the upper tracts, and maintaining
      stable renal function. It provides for a functional sphincterotomy without the
      significant complications of hematuria and erectile dysfunction that can result
      from the traditional endoscopic external sphincterotomy.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 7528428
TI  - Alternative surgical treatments for obstructive BPH: balloons and stents.

PMID- 7528426
TI  - Other non-medical treatments: balloons and stents.

PMID- 7528429
TI  - Retreatment rate after surgical and non-surgical treatments.

PMID- 7528430
TI  - International consultation on benign prostatic hyperplasia.

PMID- 7528431
TI  - The assessment of patient complaints.
AB  - The objective documentation of patient symptom level is one of the most essential
      part of its recommendation for the diagnosis, evaluation, work-up, and eventual
      treatment of patients with prostatism. The AUA Symptom Score is an appropriate
      system, and should be adopted as the standard instrument during evaluation and
      follow-up. However, it should be remembered that the symptoms of BPH are not
      specific. In fact, age-matched women have similar symptoms and equal severity of
      symptoms when evaluated with the AUA symptom score instrument (Chai, Belville et
      al., 1993; Chancellor and Rivas, 1993; Lepor and Machi, 1993). This does not take
      away from the usefulness of the AUA symptom score which was not developed to
      diagnose BPH, but rather to measure objectively the severity of symptoms, and to
      follow the progression or improvement of symptoms following treatment. Thus,
      disease specificity is not a prerequisite for the usefulness of a symptom score
      used in this capacity. Additional evaluation by urodynamics may be necessary in
      selected cases. It should be emphasized that optimal treatment decisions for
      individual patients will also need to take into account how a given level of
      symptoms affects that patient's quality of life (bothersomeness).

PMID- 7528432
TI  - Signs and symptoms of benign prostatic hyperplasia in men screened for prostatic
      carcinoma.

PMID- 7528434
TI  - Development of voltage-dependent and ligand-gated channels in excitable
      membranes.

PMID- 7528433
TI  - Naloxone reduces the feeding evoked by intracerebroventricular galanin injection.
AB  - Central injection of galanin elicits feeding in satiated rats. We recently
      observed galanin-immunoreactive fibers in synaptic connection with a population
      of beta-endorphin-immunopositive cell bodies and dendrites in the basal
      hypothalamus. Because beta-endorphin also stimulates food intake, these
      morphological findings raised the possibility that stimulation of feeding by
      galanin may, in part, be mediated by beta-endorphin release. First, we observed
      that ICV injection of galanin (1.5-6.0 nmol) stimulated feeding in a dose-related
      fashion. Next, the effect on food intake of the opioid receptor antagonist
      naloxone (20-200 micrograms, ICV) administered immediately preceding galanin (3
      nmol, ICV) was evaluated. Galanin-induced feeding was suppressed by naloxone in a
      dose-dependent manner with a maximal suppression of 76% at the highest naloxone
      dose. These findings support the existence of a functional link between galanin
      and beta-endorphin and are in accord with the view that stimulation of food
      intake by galanin may, in part, be mediated by increased beta-endorphin release.

PMID- 7528435
TI  - Role of GH and IGF-I in the regulation of IGF-I, IGF-I receptor and IGF binding
      protein gene expression in the rat spleen.
AB  - To characterize the expression of the IGF-I system in the spleen and its role in
      spleen growth, we have studied the effect of hypophysectomy and the action of
      either GH or IGF-I treatment on the expression of several components of the IGF
      system in the rat. Female Sprague-Dawley rats were hypophysectomized (Hx) on
      postnatal day 50, and five animals each received twice-daily sc injections of
      saline, bovine GH (bGH; 84 micrograms/animal/day), or recombinant human IGF-I
      (rhIGF-I; 125 micrograms/animal/day) for 11 days. Compared to sham-operated
      controls, Hx animals exhibited a reduction in both body (192.6 +/- 5.6 g (mean +/
      S.E.M.) vs. 268.6 +/- 6.0 g; P < 0.001) and spleen weights (0.42 +/- 0.03 g vs.
      0.84 +/- 0.06 g; P < 0.001). The reduction in body and spleen weights in Hx
      animals was partially prevented by both bGH and rhIGF-I. Body weights were 234.2
      +/- 5.3 g (P < 0.001) after bGH and 213.8 +/- 6.3 g (P < 0.05) after rhIGF-I.
      Spleen weights were 0.56 +/- 0.048 after bGH P < 0.01 and 0.53 +/- 0.05 g after
      rhIGF-I (P < 0.05). Serum GH and IGF-I levels were markedly reduced in Hx animals
      and bGH partially maintained IGF-I levels. Hypophysectomy reduced spleen IGF-I
      mRNA levels (30.6 +/- 7.5% of control values; P < 0.05) and this reduction was
      prevented by bGH (96.6 +/- 24.2%; NS) but not by rhIGF-I (39.9 +/- 5.0% NS vs.
      Hx). There were no changes in GH receptor or IGF-I receptor mRNA levels in Hx or
      bGH or rhIGF-I-treated animals. When IGF-I binding protein (IGFBP) mRNA levels
      were studied under these conditions, we found that IGFBP-1 mRNA was not detected
      in spleen; IGFBP-2 mRNA levels were reduced in Hx rats (67.9 +/- 7.4% of control
      values, P < 0.05) and bGH treatment prevented this reduction (95.5 +/- 12.2%,
      NS). IGFBP-3 mRNA levels were not affected by hypophysectomy or by bGH treatment,
      but were reduced in rhIGF-treated rats (69.6 +/- 3.0%, P < 0.05). On the other
      hand, IGFBP-4 mRNA levels were increased in Hx rats (136.4 +/- 15.9% of control
      values, P < 0.05) and bGH treatment prevented this increase.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7528436
TI  - A new gonadotropin-releasing hormone (GnRH) superagonist in goldfish: influence
      of dialkyl-D-homoarginine at position 6 on gonadotropin-II and growth hormone
      release.
AB  - The two native forms of gonadotropin-releasing hormones (GnRH) present in
      goldfish, salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), stimulate
      gonadotropin-II (GTH-II) and growth hormone (GH) release both in vivo and in
      vitro. In our previous study using perifused goldfish pituitary fragments, many
      mammalian GnRH antagonists, especially those with D-Arg6, showed weak to strong
      stimulation of GTH-II and GH release. In the present study, the dose-related
      stimulation of GTH-II and GH release by [Ac-D(2)-Nal1, 4Cl-D-Phe2, D-Trp3, D
      Arg6, Trp7, D-Ala10] mGnRH (analog J) and [Ac-D(2)-Nal1, 4Cl-D-Phe2, D-Trp3, D
      hArg(Et2)6, D-Ala10] mGnRH (analog K) was demonstrated; the stimulatory potency
      of both analogs was significantly lower than that of native sGnRH. In the
      presence of analogs J and K, cGnRH-II stimulated GTH-II release was significantly
      suppressed. Further, GTH-II and GH stimulation by 2 microM of analog K was
      significantly suppressed by a 'true' GnRH antagonist, [Ac-delta 3-Pro1, 4FD-Phe2,
      D-Trp3,6] mGnRH (analog E). These results indicate that analogs J and K increase
      GTH-II and GH release in goldfish by acting on GnRH receptors on gonadotrophs and
      somatotrophs. Since analog K, having [D-hArg(Et2)6], strongly stimulated GTH-II
      release, the potency of [D-hArg(Et2)6] or [D-hArg(CH2CF3)2(6)] substituted
      analogs to stimulate GTH-II and GH release from the perifused goldfish pituitary
      fragments was tested. Among the peptides tested, [D-hArg(Et2)6, Pro9-NHEt] sGnRH
      had a higher potency in stimulating GTH-II release than any other analog tested
      in the present or in previous studies. For stimulation of GH release, [D
      hArg(Et2)6, Pro9-NHEt] sGnRH and [D-Arg6, Pro9-NHEt] sGnRH were the most potent
      analogs tested; analogs of mGnRH were less potent than sGnRH, indicating the
      importance of Trp7, Leu8 residues in the native peptide. These results suggest
      the importance of [D-Arg6] or alkylated [D-Arg6] in determining the intrinsic
      activity and potency of GnRH peptides in goldfish.

PMID- 7528439
TI  - [Therapy with interferon in HIV-infected patients with chronic viral hepatitis].

PMID- 7528437
TI  - N-terminally elongated fragments of galanin(1-16) inhibit insulin secretion from
      isolated mouse islets.
AB  - The neuropeptide galanin inhibits insulin secretion and has been suggested to be
      an adrenergic co-transmitter in the endocrine pancreas. Recently, N-terminally
      elongated forms of galanin have been identified in both porcine brain and
      adrenals. Whether these elongated peptides show galanin-like biological effects
      is not known. We therefore synthesized two N-terminally elongated fragments of
      galanin(1-16), which contains the active site of galanin. The synthesized
      peptides were galanin(-9-16) and galanin(-7-16), which correspond to amino acids
      24-61 and 26-61 in the galanin precursor molecule. Both these peptides were found
      to potently inhibit glucose-(11.1 mM)-stimulated insulin secretion from isolated
      mouse islets of Langerhans in all concentrations studied (1-1000 nM) (P <
      0.0001). The potency of the peptides was not different from that of synthetic rat
      galanin. Thus, at 100 nM, insulin secretion was inhibited by galanin(-7-16) by 83
      +/- 7% and by galanin(-9-16) by 71 +/- 17% and by rat galanin by 93 +/- 4% (not
      statistically different). Furthermore, the galanin receptor antagonist, M35 (10
      nM), prevented the inhibitory action of the two N-terminally galanin fragments.
      This study thus shows that N-terminally elongated galanin-fragments as entire
      galanin inhibits insulin and thus indicates that the effect of galanin on insulin
      secretion is not dependent on a free amino-terminus.

PMID- 7528438
TI  - The effect of a single intraperitoneal dose of hrIL-1 alpha on substance P-,
      neurokinin A-, calcitonin gene-related peptide- and neuropeptide Y-like
      immunoreactivity in cerebrospinal fluid, plasma and knee joint synovial fluid in
      the rat.
AB  - Substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)-
      and neuropeptide Y (NPY)-like immunoreactivity (-LI) was studied in rats'
      cerebrospinal fluid (CSF), plasma and synovial fluid (SF) from both knee joints
      at 2 and 24 h following an intraperitoneal administration of 0.05 ml human
      recombinant interleukin-1 alpha (i.p. hrIL-1 alpha) or saline. Increased or
      decreased levels of SP-, NKA and CGRP-LI were detected in CSF and plasma, whereas
      NPY-LI was unaffected. In SF only CGRP-LI increased bilaterally. There was a
      correlation in CGRP-LI content between plasma and CSF following i.p. hrIL-1 alpha
      but not between plasma and SF or CSF and SF. It can be concluded that (1) i.p.
      hrIL-1 alpha activates somatosensory afferents thereby increasing SP- and CGRP-LI
      content in CSF and plasma and NKA-LI in CSF; 2) i.p. hrIL-1 alpha induces a
      bilateral increase of CGRP-LI in SF which is not mediated through systemic
      circulation and is possibly a part of the general host defensive reaction.

PMID- 7528440
TI  - Establishment and characterization of two new Kaposi's sarcoma cell cultures from
      an AIDS and a non-AIDS patient.
AB  - We have established and characterized two new Kaposi's sarcoma (KS) cell lines
      derived from skin biopsies: AIDS-KSISTIV (from an AIDS-associated KS) and
      KSISTVIII (from a sporadic KS). AIDS-KSISTIV and KSISTVIII are composed mostly of
      spindle-shaped cells. They show similar patterns of immunohistochemical staining
      and are positive for smooth muscle (smooth muscle alpha-actin) and fibroblastoid
      (TE7) markers. Neither of these lines express the endothelial marker von
      Willebrand factor VIII. These immunohistochemical patterns are similar to
      numerous other KS lines that we and others have established. When seeded on a
      reconstituted basement membrane ("Matrigel"), AIDS-KSISTIV and KSISTVIII cells
      form branching colonies and invade into the Matrigel, as do other KS cultures
      that we have previously examined. This behaviour on Matrigel is similar to that
      of malignant sarcoma cells of different origin. The expression of vimentin and
      the morphology of the invasive colonies on Matrigel suggest that KS-derived cells
      are poorly differentiated mesenchymal cells. KS lesions are characterized by a
      conspicuous neovascularization, which appears to be derived from host cell
      recruitment. We tested the capability of the KS-cell supernatants to induce an
      angiogenic response in vitro. The new lines are able to stimulate human
      endothelial cell chemotaxis and invasion through Matrigel-coated filters. No
      differences in angiogenic potential in vitro were observed between the AIDS and
      the non-AIDS case, as we previously noted for other established cultures. Our new
      lines have the properties of true KS cells and confirm that KS spindle cells from
      HIV-positive or -negative patients have identical phenotypic and behavioural
      characteristics in vitro.

PMID- 7528441
TI  - Current concepts of immune interventions in children with respiratory diseases.
AB  - In addition to their role in oxygen transport and ventilation, the lungs serve as
      an important defense function consisting of nonspecific and specific components.
      The nonspecific factors include aerodynamic filtration, mucociliary apparatus,
      bronchoalveolar fluid flow and lymphohematogenous drainage (anatomic systems) as
      well as phagocytosis and inflammation; the specific factors include B-cell
      immunity (IgG, A, M, D and E) and T-cell immunity (cell-mediated immunity). In
      the lungs, specialized lymphoid tissues in contact with epithelium (bronchus
      associated lymphoid tissues; BALT) function in local antibody (secretory IgA) and
      cell-mediated immunity responses to foreign antigens. Based upon these
      considerations, a number of therapeutic interventions have been developed to
      enhance various components of lung defense. These include substances which
      enhance both nonspecific elements (leukocyte transfusion, plasma, nonspecific
      immunostimulants, e.g., immunoactive bacterial extracts) as well as specific
      elements (vaccines, intravenous gammaglobulin, plasma, interferons, cytokines).
      The need for further development and utilization of new immune interventions is
      underscored by the large number of infants and children who suffer from recurrent
      respiratory infections, who have either maturational immaturity (e.g. small for
      gestational age newborn), genetically determined (e.g. cystic fibrosis) or
      acquired defects (e.g. AIDS) of lung defense mechanisms. The emergence of
      antibiotic-resistant bacterial organisms, e.g. Streptococcus pneumoniae, poses an
      additional need for new immune interventions.

PMID- 7528442
TI  - Surgical critical care for cancer patients.
AB  - Progress in cancer surgery and changes in philosophy have resulted in greater
      numbers of critically ill surgical oncology patients. The effects of cancer and
      prior exposure to cancer therapies increase the risks for postsurgical problems.
      Life-threatening cardiopulmonary sequela and patients undergoing liver resections
      and transplantation are examples of problems that require the knowledge and skill
      of critical care nurses. Critical care surgical nurses face new challenges by
      merging their surgical nursing expertise with principles of cancer care.

PMID- 7528443
TI  - Upregulation of complement regulators MCP (CD46), DAF (CD55) and protectin (CD59)
      in arthritic joint disease.
AB  - CD46, CD55 and CD59 are cell surface glycoproteins which are widely distributed
      on normal tissue, where they function in the prevention of complement-mediated
      damage. In this study we have investigated the altered expression of these
      molecules under inflammatory conditions both in vitro and in vivo. By using
      immunocytochemical techniques we demonstrated marked but disparate upregulation
      of these molecules in IL1-treated cartilage and in diseased cartilage from
      arthritic joints compared to normal cartilage in both humans and pigs. Expression
      of these proteins was restricted to the chondrocyte surface, and was also
      demonstrated on isolated chondrocytes grown in monolayer culture and stimulated
      with IL1. It is suggested that the elevated levels of these regulatory proteins
      may be necessary to ameliorate the multiple damaging effects of the inflammatory
      processes associated with destructive joint diseases.

PMID- 7528444
TI  - Splicing of the rolA transcript of Agrobacterium rhizogenes in Arabidopsis.
AB  - The rolA gene encoded on the Ri plasmid A4 of Agrobacterium rhizogenes is one of
      the transferred (TL-DNA) genes involved in the pathogenesis of hairy-root disease
      in plants. The function of the 100-amino acid protein product of rolA is unknown,
      although its expression causes physiological and developmental alterations in
      transgenic plants. The rolA gene of A. rhizogenes contains an intron in its
      untranslated leader region that has features typical of plant pre-messenger RNA
      introns. Transcription and splicing of the rolA pre-messenger RNA occur in the
      plant cell.

PMID- 7528445
TI  - A unified polymerase mechanism for nonhomologous DNA and RNA polymerases.

PMID- 7528446
TI  - The use of hematopoietic growth factors for high-dose chemotherapy and peripheral
      blood progenitor cell transplantation.

PMID- 7528447
TI  - Recombinant human granulocyte-macrophage colony-stimulating factor as adjunct to
      chemotherapy in aggressive non-Hodgkin's lymphomas.

PMID- 7528448
TI  - Dose-intensified therapy combined with autologous blood stem cell support in
      patients with multiple myeloma.

PMID- 7528452
TI  - [The loneliness of the dying].

PMID- 7528450
TI  - Chemotherapy dose-escalation with hemopoietic growth factor support in ovarian
      cancer.

PMID- 7528451
TI  - [The post-adenomectomy dysuria-hematuria syndrome].
AB  - The dysuria syndrome consists of the persistence or accentuation following
      adenomectomy of the symptoms which caused the patient to seek the urologist's
      advice. It is frequent event whose causes are largely connected to
      physiopathological events which are also influenced by the developing role
      between the urologist and patients in view of prostate disease. The authors
      analyse the various causes of post-adenomectomy dysuria and emphasise the
      importance of a precise diagnosis and the correct indications for surgery for the
      prevention of this disease.

PMID- 7528453
TI  - Cat scratch disease.

PMID- 7528454
TI  - [Basic principles of intensive radiotherapy in oncologic patients with
      unfavorable prognosis].
AB  - The authors discuss variants of intensive radiotherapy of oncologic patients with
      an unfavourable prognosis in different situations. Recommendations are offered
      concerning the rational choice of irradiation volume, dose-time relationships,
      combination of local and large-field subtotal exposure.

PMID- 7528449
TI  - New perspectives in the treatment of acute myeloid leukemia by hematopoietic
      growth factors.
AB  - The application of hematopoietic growth factors in the treatment on acute myeloid
      leukemia (AML) may principally aim at shortening the period of treatment
      associated neutropenia and reducing the rate of infectious complications by their
      post-therapeutic administration but may also be used to increase the sensitivity
      of leukemic blasts to antileukemic therapy by pretherapeutic growth stimulation.
      Both aspects were addressed in subsequent clinical phase II studies and
      preclinical investigations. In a first clinical trial, 36 patients with high-risk
      AML received granulocyte-macrophage colony-stimulating factor (GM-CSF) after
      successful cytoreductive chemotherapy and experienced a shortening of the period
      of post-therapeutic neutropenia by 6 to 9 days, leading to a significant
      reduction of treatment-associated deaths from 39% to 14%. In preclinical studies
      an enhancement of the cytotoxicity of cytosine arabinoside (AraC) on leukemic
      blasts could be shown by pretreatment with GM-CSF or IL-3. Investigations on the
      impact of hematopoietic growth factors on the intracellular metabolism of AraC
      indicated that this effect was primarily mediated by an increase in the activity
      of DNA-polymerase-alpha. The evaluation of different doses of AraC showed the
      most marked increase after the combination of GM-CSF with conventional rather
      than high doses of AraC. Based on these preclinical experiments, a prospective
      randomized trial was subsequently initiated investigating the effect of GM-CSF
      before and during induction, consolidation, and the first two cycles of
      maintenance chemotherapy in newly diagnosed AML. This ongoing trial has enrolled
      67 patients at the current time. An early interim analysis showed no differences
      in remission rates but a tendency toward a longer remission duration in patients
      receiving GM-CSF. These data indicate that hematopoietic growth factors like GM
      CSF in particular may provide a new perspective in the treatment of acute myeloid
      leukemia with the possibility of reducing treatment associated mortality and
      perhaps of increasing the efficacy of antileukemic treatment.

PMID- 7528455
TI  - Stability of glycoproteins Ib/IX and IIb/IIIa during preparation and storage of
      platelet concentrates: detection by binding assays with epitope-defined
      monoclonal antibodies and physiological ligands.
AB  - Preservation of the glycoprotein (GP) complexes Ib/IX and IIb/IIIa, because of
      their role as specific platelet receptors for adhesive proteins, is essential for
      the haemostatic efficacy of transfusions of platelet concentrates (PCs). We have
      combined binding assays with epitope-defined monoclonal antibodies, and with the
      physiological ligands von Willebrand factor and fibrinogen (Fo), to investigate
      the total expression and functional status of these receptors, in PCs stored for
      up to 9 days. Routine preparation and storage for up to 5 days have no apparent
      effect on the surface expression and the functional status of GPs Ib/IX and
      IIb/IIIa. However, after prolonged storage for up to 9 days we found a 50%
      decrease in the level of the total and functional GP Ib/IX content of platelets.
      This finding parallelled a significant rise in plasma glycocalicin, a proteolytic
      fragment of GP Ib. In addition, long-term storage promoted an impairment in the
      exposure of GP IIb/IIIa to Fo, and a 50% decrease in Fo binding capacity, without
      affecting the complex quantitatively. Finally, we also noticed a storage-induced
      increase in the platelet surface expression of GMP 140, and after 9 days of
      storage there was a rise in mean platelet volume, and a significant reduction in
      pH levels.

PMID- 7528456
TI  - Incidence of post-transfusion hepatitis before and after screening for hepatitis
      C virus antibody.
AB  - To evaluate the effectiveness of screening test for antibody to hepatitis C virus
      (anti-HCV), the incidence of acute post-transfusion HCV infection in patients who
      underwent cardiovascular surgery and received blood transfusion was studied. All
      patients were followed prospectively with serum biochemistry tests and viral
      hepatitis markers before and periodically for at least 6 months after
      cardiovascular surgery. None of them had history of liver disease and none tested
      positive for anti-HCV prior to blood transfusion. Before blood donors were
      screened for anti-HCV with a second-generation HCV diagnostic kit, 28 (12.4%) of
      226 patients or 0.49% of 5,690 unit transfusion had seroconverted to anti-HCV
      during a 6-month follow-up. The incidence of post-transfusion hepatitis (PTH) C
      in 91 patients who had received 1-12 units transfusion was significantly lower
      than in 135 patients who had received more than 12 units transfusion (6.6 vs.
      16.3%, p < 0.05). However, none of the 87 transfused patients, since anti-HCV
      screening in July 1992, developed PTH C (p < 0.05). The result demonstrates that
      screening for anti-HCV by a more sensitive second-generation HCV diagnostic assay
      may protect the patients studied from PTH C. It further provides a firm argument
      for the necessity of a nation-wide blood donor screening.

PMID- 7528457
TI  - [Total cavopulmonary anastomosis: risk factors and results in patients under 4
      years of age].
AB  - In recent years, an increasing number of modified Fontan-operations has been
      performed in children younger than 4 years of age. The purpose of this study was
      to identify preoperative risk factors in this age group. From February 1990 until
      February 1993, we performed in our center a modified Fontan-operation using the
      technique of total cavopulmonary anastomosis (TCPA) in 37 consecutive patients
      (17 pts. < 4 years = group I, 20 pts. > 4 years = group II). Early postoperative
      mortality occurred in patients of group I only (n = 3 pts.). All of these
      patients had additional preoperative risk factors. Pulmonary vascular resistance
      (PVRI) > 2 U x m2 was a significant risk factor for the younger patients while
      pulmonary artery size alone (expressed as the McGoon-ratio or Nakata-index) could
      not be identified as a separate risk factor. Using two additional indices (McGoon
      ratio/PVRI and Nakata-index/PVRI), we were able to identify patients with
      unfavorable postoperative hemodynamics as high-risk patients. In our experience,
      TCPA can be performed in patients younger than 4 years of age with a low
      mortality, if there are no additional preoperative risk factors. For high-risk
      patients we recommend either a bidirectional Glenn-anastomosis as a first step
      procedure or a TCPA with fenestration of the intraatrial tunnel-patch.

PMID- 7528458
TI  - [Use of terazosin and alfuzosin in the treatment of benign prostatic hypertrophy
      (BPH): our experience].
AB  - Dynamic and static factors cause infravesical obstruction in men with BPH. The
      dynamic component is determined by alpha 1-adrenoceptor-mediated contractions of
      the prostate smooth muscle and bladder neck. Using alpha-receptor-blockers will
      relieve bladder outlet obstruction, improving urinary flow rates and obstructive
      and irritative symptoms as well as the physician's global assessment. This study
      was performed to evaluate the efficacy and safety of alpha 1 blockers (terazosin
      and alfuzosin) in ambulatory patients (n = 20) with BPH. After 24 weeks of
      therapy, the peak flow rate increased 54% from a baseline average of 8.5 ml/s to
      13.1 ml/s (p < 0.01). The mean flow rate increased 49%, from a baseline of 4.61
      ml/s to 6.9 ml/s (p < 0.01); residual volume decreased 74% from 48.3 ml to 12.5
      ml (p < 0.001). Mean systolic blood pressure decreased significantly (p < 0.05)
      from baseline, but this change wasn't clinically important. The clinical
      experience with alpha-blockers in BPH indicates that these drugs increase urinary
      flow rates, decrease obstructive and irritative symptoms, without serious side
      effects.

PMID- 7528459
TI  - Influence of epithelium removal on allergic contraction of isolated tracheal
      smooth muscle.
AB  - Sensitized guinea pig tracheal preparations with epithelium removed were more
      sensitive to acetylcholine, histamine substance P, and barium chloride than those
      with epithelium intact. EC50 of them obtained in the preparations with epithelium
      removed dramatically decreased to 1/6-1/30 vs that obtained in epithelium intact
      ones. The amplitudes of contractions of epithelium-removed preparations induced
      by antigen-antibody reaction or electric field stimulation increased by 50%-100%
      vs the control. These results indicated that the epithelium had important
      modulative effects on the airway, especially on its allergic contractions.

PMID- 7528461
TI  - Psychotropic medications in oncology and in AIDS patients.
AB  - This chapter has reviewed the prevalence of cancer and of psychiatric syndromes
      in the cancer setting. Guidelines have been given for the evaluation and
      treatment of specific psychiatric syndromes, as well as several special problems
      found in the cancer setting. In general, the major principle of using psychiatric
      medications in the patient with cancer or advanced AIDS is to use them to improve
      comfort, and not to withhold them when they may be of benefit.

PMID- 7528460
TI  - Photoreceptor-specific proteins in the mammalian pineal organ: immunocytochemical
      data and functional considerations.
AB  - The mammalian pineal organ contains photoreceptor-specific proteins, whose
      distribution shows conspicuous variation among different species of mammals.
      Nevertheless, the following general conclusions can be drawn: immunoreactions for
      S-antigen and recoverin labeled more pinealocytes than the rod-opsin
      immunoreaction. The intensity of the recoverin- and S-antigen immunoreactions
      varied from cell to cell. alpha-Transducin immunoreaction was absent from the
      pineal organ of all mammals investigated with the exception of the blind mole
      rat. Immunoreaction for the cyclic GMP-gated cation channel was undetectable in
      the pineal organ of all mammals investigated. The functional significance of
      photoreceptor-specific proteins in the mammalian pineal organ remains unknown. It
      has been speculated that the S-antigen might be involved in adrenergic
      transduction mechanisms. To test this assumption, we have started to analyze
      calcium responses of single rat pinealocytes to norepinephrine stimulation using
      the Fura-2 technique. The cells were subsequently labeled by means of S-antigen
      immunocytochemistry. These combined investigations showed that variation in S
      antigen immunoreactivity is not correlated with differences in the rapid calcium
      response to stimulation with norepinephrine. It remains to be determined whether
      cells displaying different intensities of the S-antigen immunoreaction show
      different cyclic AMP responses to noradrenergic stimulation. Investigations along
      this line should help to clarify further whether there is indeed a relation
      between the expression of S-antigen and noradrenergic transduction mechanisms in
      the mammalian pineal organ.

PMID- 7528462
TI  - [The course and limitation of medical treatment for benign prostatic
      hyperplasia].
AB  - To clarify the effects and limitation of medical treatment for benign prostatic
      hyperplasia (BPH), 2,476 patients with BPH were analyzed in terms of symptoms,
      objective findings, treatment modality and whether surgery was required during
      the course of medical treatment. As initial therapy, 1,320 cases (53.3%) were
      treated with medicine and 783 cases (31.6%) underwent surgery. In the group of
      patients initially treated with medicine, 264 cases (20.0%) required surgery and
      most operations were performed within six months from the start of medical
      treatment. Those who required surgery had a larger prostate and more residual
      urine than those who continued medical treatment. This tendency was also observed
      in the patients treated with antiandrogen. Therefore, medical therapy might be
      inappropriate to treat the patients with more than 50 ml of residual urine or
      significantly large prostate such as goose egg sized or larger. In conclusion,
      medical treatment possessed potential usefulness for the management of BPH,
      however, there seemed to be limitation of the effects of medical treatment.

PMID- 7528463
TI  - [Semi-radical transurethral resection of the prostate for small benign prostatic
      hyperplasia].
AB  - The conventional method of transurethral resection of the prostate (TUR-P) is
      often not beneficial for small benign prostatic hyperplasia (BPH) because of a
      high frequency of postoperative bladder neck contracture (BNC). Herein, we
      examined the usefulness of semi-radical transurethral resection of the prostate
      (semi-radical TUR-P) from the view points of improvement of peak flow rate, the
      frequency of postoperative BNC and incidental carcinoma of the prostate in 79
      cases of small BPH (group A) and 101 cases (group B) of large BPH in which less
      than 10 g for more than 10 g of the internal glands was resected, respectively.
      The bladder neck was resected carefully to avoid over resection which may cause
      BNC in small BPH cases. Satisfactory results were obtained in both groups, that
      is, the improvement of the peak flow rate from 7.03 +/- 3.79 ml/sec to 13.9 +/-
      7.32ml/sec and from 4.96 +/- 2.88 ml/sec to 15.2 +/- 8.30 ml/sec, and the
      frequency of BNC were 2.53% (2/79) and 1.98% (2/101) in groups A and B,
      respectively. The frequency of incidental carcinoma of the prostate were 15.2%
      (12/79) and 17.8% (18/101) in groups A and B. We conclude that semi-radical TUR-P
      is a favorable maneuver for small BPH because of satisfactory improvement in peak
      flow rate with low frequency of postoperative BNC and its superiority in
      screening test for incidental carcinoma of the prostate.

PMID- 7528464
TI  - Impaired endothelium-dependent vascular relaxation in patients with
      hypercholesterolemia extends beyond the muscarinic receptor.
AB  - Patients with hypercholesterolemia have impaired endothelium-dependent
      vasodilation. However, previous human studies have invariably used muscarinic
      agents to assess endothelial function. The purpose of this investigation was to
      determine whether impaired endothelium-dependent vasodilation of
      hypercholesterolemic patients is related to a specific and isolated defect of the
      muscarinic receptor, or to a broader abnormality of the endothelial cells. The
      forearm vascular responses to the endothelium-dependent agents acetylcholine
      (7.5, 15, and 30 micrograms/min) and substance P (1, 2, and 4 pmol/min), and to
      the direct smooth muscle dilator sodium nitroprusside (0.8, 1.6, and 3.2
      micrograms/min) were studied in 16 hypercholesterolemic patients (8 men and 8
      women; age [mean +/- SD] 50 +/- 7 years; serum cholesterol > 250 mg/dl) and 16
      normal volunteers (8 men and 8 women; age 47 +/- 8 years; serum cholesterol < 200
      mg/dl). Drugs were infused into the brachial artery and the response of the
      forearm vasculature was measured by strain-gauge plethysmography. The vasodilator
      response to acetylcholine was reduced in hypercholesterolemic patients compared
      with normal controls; at the highest dose (30 micrograms/min) the increase in
      forearm blood flow was 13.5 +/- 7 ml/min/100 ml in controls and 7.54 +/- 6 in
      patients (p < 0.05). The response to substance P was also blunted in
      hypercholesterolemic patients; at the highest dose (4 pmol/min), the increase in
      forearm blood flow was 12.1 +/- 5 ml/min/100 ml in controls and 7.6 +/- 4 in
      patients (p < 0.03). A significant correlation was found between the highest
      blood flow responses with acetylcholine and with substance P (r = 0.58; p <
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528466
TI  - The relative sensitivity of special stains and culture in open lung biopsies.
AB  - The author compared the efficacy of Gram's, methenamine silver, and acid-fast
      stains on tissue sections to conventional culture methods in vitro for detecting
      infection in 110 open lung biopsies (99 inflammatory, 11 neoplastic). Twenty-one
      cases of clinically significant infection were found (19%). Gram's stain and
      culture had sensitivities of 100% and 80%, respectively. However, 21 of the
      cultures grew clinically irrelevant organisms and 2 Gram's stains originally were
      misinterpreted. In contrast, methenamine silver and acid--fast stains were
      significantly more sensitive (80% and 100%) than their corresponding cultures
      (20% and 50%) and no methenamine silver or acid-fast stains were misinterpreted.
      In addition, methenamine silver stain had a higher positive predictive value than
      culture (100% vs. 60%). In conclusion, both methenamine silver and acid-fast
      stains are more sensitive than culture for detecting significant pathogens from
      open lung biopsies. Gram's stain is as sensitive as bacterial culture but is
      often misinterpreted. Moreover, interpretation of bacterial cultures is
      complicated by the frequent growth of clinically insignificant organisms.

PMID- 7528465
TI  - Surgical pathology and the diagnosis of infectious diseases.

PMID- 7528467
TI  - Hepatocellular expression of HLA-A, B, C molecules predicts primary response to
      interferon in patients with chronic hepatitis C.
AB  - Primary response rate to alpha-interferon (IFN) is about 50% in patients with
      chronic hepatitis C. Criteria for predicting a positive primary response are
      lacking. HLA-A,B,C molecule expression is known to be stimulated by viral
      infections. In 36 consecutive interferon-treated anti-HCV positive patients with
      an available frozen liver biopsy sample, the predictive value of liver HLA-A,B,C
      expression, and of histologic, clinical, and biochemical parameters was
      evaluated. Response to treatment was defined by normalization of transaminases,
      and disappearance of serum HCV-RNA within 3 months. According to these criteria,
      17 patients were classified as nonresponders and 19 were classified as
      responders. The pattern of HLA-A,B,C hepatocellular positivity varied from normal
      (negative or occasional faint staining of hepatocellular membranes) to diffuse,
      strong "honeycomb" positivity. The highest scores of positivity were found in
      nonresponder patients. The discriminant capacity of HLA-A,B,C scores of
      positivity was compared with clinical, biochemical and histologic parameters by
      discriminant analysis. HLA-A,B,C expression was found to be the main discriminant
      parameter, in addition to alkaline phosphate (ALP) and gamma-glutamyl
      transpeptidase (GGT) which added little additional information. The higher
      hepatocellular expression of class I MHC molecules in nonresponder cases may
      reflect a different viral effect on hepatocytes, which is induced by different
      HCV genotypes or levels of viremia. From a clinical point of view, the
      pretreatment HLA-A,B,C pattern of positivity represents a powerful tool in the
      selection of patients for interferon treatment.

PMID- 7528468
TI  - Utility of cytokeratin immunostaining in separating pulmonary adenocarcinomas
      from colonic adenocarcinomas.
AB  - Adenocarcinomas of uncertain origin are a frequent problem for surgical
      pathologists. To determine the utility of immunostaining for cytokeratin 7 and
      cytokeratin 20 in the separation of pulmonary adenocarcinomas from colonic
      adenocarcinomas, we studied routinely processed, formalin-fixed tissue from 151
      of these tumors using commercially available monoclonal antibodies and an avidin
      biotin immunohistochemical technique. Used alone, neither cytokeratin 7
      immunostaining or cytokeratin 20 immunostaining reliably separated these tumors.
      However, the immunophenotype of cytokeratin 7 positive/cytokeratin 20 negative
      was seen in 86% of the pulmonary adenocarcinomas, and in 0% of the colonic
      adenocarcinomas. Conversely, the cytokeratin 7-negative/cytokeratin 20-positive
      immunophenotype was seen in 77% of the colonic carcinomas, and in 0% of the
      pulmonary tumors. In conclusion, cytokeratin 7/cytokeratin 20 immunostaining
      patterns may be helpful in separating pulmonary adenocarcinomas from colonic
      adenocarcinomas.

PMID- 7528469
TI  - The lipase to amylase ratio in acute pancreatitis.
AB  - OBJECTIVES: The ratio of serum lipase to serum amylase has been proposed to
      distinguish acute episodes of alcoholic from nonalcoholic pancreatitis. We
      evaluated the efficacy of this test in a community hospital setting. METHODS:
      Charts of all patients discharged with a diagnosis of acute pancreatitis over 19
      months were retrospectively reviewed. Patients were excluded if their creatinine
      was greater than 3.0 mg/dl, if the amylase and lipase were not measured within 72
      h of the onset of symptoms, or if the cause of pancreatitis was not known by the
      time of discharge. RESULTS: Of the 56 patients, 31 had alcoholic pancreatitis.
      The lipase to amylase ratio did not differ significantly between patients with
      alcoholic and nonalcoholic pancreatitis. Median amylase and lipase were
      significantly higher in nonalcoholic pancreatitis; however, the wide ranges of
      both meant that neither amylase nor lipase accurately determined the cause of
      pancreatitis. CONCLUSION: The lipase to amylase ratio does not appear to be
      sufficiently sensitive or specific to distinguish alcoholic from nonalcoholic
      acute pancreatitis.

PMID- 7528470
TI  - Renal medullary carcinoma. The seventh sickle cell nephropathy.
AB  - Over the last 22 years, we have encountered 34 examples of a highly aggressive
      neoplasm with a microscopic morphology that is highly predictive of finding
      sickled erythrocytes in the tissue. With the exception of one patient, all are
      believed to have had sickle cell trait or, in one case, hemoglobin SC disease.
      These 33 patients are the subject of this report and, where their race was known,
      they were all blacks between the ages of 11 and 39 years. Between the ages of 11
      and 24 years, males predominated by 3 to 1. Beyond age 24, however, the tumors
      occurred equally in men and women. The dominant tumor mass was in the medulla and
      ranged from 4 to 12 cm in diameter. Mean size was 7 cm; median, 6 cm. Peripheral
      satellites in the renal cortex and pelvic soft tissues, as well as venous and
      lymphatic invasion, were usually present. The lesions exhibited a reticular, yolk
      sac-like, or adenoid cystic appearance, often with poorly differentiated areas in
      a highly desmoplastic stroma admixed with neutrophils and usually marginated by
      lymphocytes. The tumors had usually metastasized when first discovered, and none
      was confined to the kidney at the time of nephrectomy. The mean duration of life
      after surgery was 15 weeks. These tumors probably arise in the calyceal
      epithelium in or near the renal papillae, the same site that produces the more
      familiar picture of unilateral hematuria in patients with sickle cell trait. We
      have concluded that renal medullary carcinoma represents another example of renal
      disease associated with sickle cell disorders. The other six are unilateral
      hematuria, papillary necrosis, nephrotic syndrome, renal infarction, inability to
      concentrate urine, and pyelonephritis.

PMID- 7528471
TI  - CD34 expression in neural and fibrohistiocytic lesions.

PMID- 7528472
TI  - Stromal tumors of the duodenum. A histologic and immunohistochemical study of 20
      cases.
AB  - Using cell size, cell density, and microscopic growth pattern, 20 duodenal
      stromal tumors were initially separated into benign and malignant categories. The
      10 histologic benign tumors had uniform spindle cells, low cellularity, and an
      organoid pattern. All had round eosinophilic collagen blobs scattered among the
      spindle cells, were 4.5 cm or less in maximum diameter, and had two or fewer
      mitoses per 50 high-power fields (HPF). None metastasized or recurred during a
      median follow-up of 7 years. In contrast, the 10 histologically malignant tumors
      were highly cellular, all had two or more mitoses per 50 HPF, and all but one had
      diameters of 4.5 cm or greater, the exception being 4 cm. Eight cases also had
      benign-appearing areas, usually submucosal. Eight patients died with disease a
      median of 31 months after resection, almost all with liver metastases. One
      patient is alive with metastasis at 13 years. The patient with the 4-cm malignant
      tumor is disease free at 49 months. All 15 cases were strongly vimentin positive,
      11 had S-100 protein, and seven had the CD34 marker. None were desmin or actin
      positive. No immunophenotype separated benign from malignant. The proliferation
      marker, proliferating cell nuclear antigen, correlated with histologic diagnosis
      and clinical outcome, but Ki-67 did not. Based on light microscopic features
      alone, benign and malignant duodenal stromal tumors can be separated from each
      other. Tumors with large cells and an organoid pattern are predictably benign; in
      this study, these tumors measured 4.5 cm or less in diameter and had fewer than 2
      mitoses per 50 HPF. Highly cellular tumors with small cells and little or no
      organoid pattern are malignant. They usually have a diameter greater than 4.5 cm
      and more than two mitoses per 50 HPF, and they are usually fatal. Immunostaining
      for cytoplasmic proteins and proliferation markers offers no additional
      prognostic information to the light microscopic appearances. These conclusions
      apply only to duodenal tumors; whether they also apply to stromal tumors of the
      jejunum and ileum is not known.

PMID- 7528473
TI  - Tricholemmal carcinoma. A clinicopathologic study of 13 cases.
AB  - We describe 13 cases of tricholemmal carcinoma, a rarely recognized cutaneous
      adnexal neoplasm. The patients were nine men and four women. In general, the
      tumors presented as slow-growing epidermal papules, indurated plaques, or nodules
      showing predilection for sun-exposed, hair-bearing skin. The lesions were most
      frequently misdiagnosed clinically as basal cell carcinoma. Histologically, they
      showed a variegation of growth patterns including solid, lobular, and trabecular;
      they were characterized by a proliferation of epithelial cells with features of
      outer root sheath differentiation, including abundant glycogen-rich, clear
      cytoplasm, foci of pilar-type keratinization, and peripheral palisading of cells
      with subnuclear vacuolization. Because of their variable growth pattern, overt
      cytologic atypia, abundant clear cytoplasm, occasional pagetoid intraepidermal
      spread, and brisk mitotic activity, these tumors may pose difficulties for
      diagnosis and be confused with other malignant skin tumors with clear cell
      changes. Despite the seemingly malignant cytological appearance of these lesions,
      clinical follow-up in 10 cases showed no recurrence or metastasis over a period
      of 2-8 years. Thus, conservative surgical excision with clear margins appears to
      be the treatment of choice for these neoplasms.

PMID- 7528474
TI  - Histopathological variants of neurofibroma. A study of 114 lesions.
AB  - Although neurofibroma is a relatively common tumor, some histopathologic variants
      are so rare that they are not well known. In a study of 130 neural cutaneous
      tumors seen between 1986 and 1991 in the department of dermatology at the
      University of Heinrich-Heine, we identified 114 neurofibromas of different types.
      We present herein the histopathological features of these tumors. The
      differentiating features from other neural tumors--melanocytic or mesenchymal
      tumors that display "neuroid" features--are also discussed. also discussed.

PMID- 7528475
TI  - Histologic spectrum of neurothekeoma and the value of immunoperoxidase staining
      for S-100 protein in distinguishing it from melanoma.
AB  - Neurothekeoma, a benign cutaneous lesion of probable nerve sheath origin, is
      divided histologically into two subtypes--myxoid and cellular. However, we
      believe that neurothekeoma encompasses a wider spectrum of lesions, with the
      myxoid and cellular subtypes falling at either end of the morphologic spectrum.
      Because the cellular variant of neurothekeoma sometimes resembles melanoma, it
      presents a difficult diagnostic problem. We report the histologic and
      immunohistochemical findings in 14 cases of neurothekeoma and review the findings
      in 35 additional cases from the literature. A detailed analysis of the histologic
      spectrum is also included. When examined by immunostains, only the myxoid
      variants of neurothekeoma stain positively for S-100 protein. We conclude that
      when the histological differential diagnosis is between cellular neurothekeoma
      and melanoma, an S-100-positive lesion should be regarded as melanoma.

PMID- 7528478
TI  - Protein epitope mapping by mass spectrometry.
AB  - A mass spectrometric method is described for the rapid mapping of linear epitopes
      in proteins that are bound by monoclonal antibodies. The method consists of three
      steps. In the first step, an antigen protein is digested by a proteolytic enzyme
      to produce an appropriate set of peptide fragments. In the second step, peptide
      fragments containing the linear epitope are selected and separated from the pool
      of peptide fragments by immunoprecipitation with the monoclonal antibody. In the
      final step, the immunoprecipitated peptides are identified by matrix-assisted
      laser desorption mass spectrometry. The method allows the rapid determination of
      antigenic sites without tedious peptide synthesis or protein mutagenesis. The
      approach is demonstrated through the mapping of epitopes in two peptides
      (melittin and glucagon-like peptide-1 7-37) against which monoclonal antibodies
      were raised. In addition to epitope mapping, the successful coupling between
      matrix-assisted laser desorption mass spectrometry and immunoprecipitation
      provides a potentially powerful tool for determining binding sites between
      proteins.

PMID- 7528477
TI  - Dermatofibroma and dermatofibrosarcoma protuberans: differential expression of
      CD34 and factor XIIIa.

PMID- 7528479
TI  - Sequence-specific gene detection with a gold electrode modified with DNA probes
      and an electrochemically active dye.
AB  - A synthesized 20-mer DNA probe complementary to a part of an oncogene v-myc
      region having a mercaptohexyl group at the 5'-phosphate end was immobilized on a
      gold electrode by chemisorption. The immobilized DNA was detected
      voltammetrically using Hoechst 33258 with a DNA minor groove binder and an
      electrochemically active dye. The modified electrode was immersed into a 100
      mumol/L Hoechst 33258 solution and washed with a phosphate buffer (pH 7.0). The
      anodic peak current (ipa) of Hoechst 33258 on the modified electrode was higher
      than that on a bare gold electrode (128 and 75 nA, respectively). It was
      considered that Hoechst 33258 was concentrated on the electrode surface due to
      its association with DNA. When the modified electrode was hybridized in a
      solution of a model targeted gene (10(-7) g/mL), single-stranded pVM623
      containing the PstI fragment of a 1.5-kilobase pair of oncogene v-myc, the ipa
      was 192 nA. On the other hand, the ipa was 128 nA when the modified electrode was
      reacted in a solution of single-stranded pUC119 without a region complementary to
      v-myc in pVM623. The ipa was related to the concentration of the targeted DNA in
      the hybridization reaction. The use of Hoechst 33258 resulted in a sequence
      specific detection of the targeted DNA quantitatively ranging from 10(-7) to 10(
      13) g/mL in a buffer solution.

PMID- 7528476
TI  - Collagenous spherulosis in a schwannoma.
AB  - "Collagenous spherulosis" is the term used to describe striking concentric and
      radiating formations of collagen in tumors. It was originally used for these
      formations in epithelial tumors of the breast and subsequently in tumors of
      salivary glands. Recently, the histologic, immunohistochemical, and
      ultrastructural features were described in a chondroid syringoma. We report a
      case of collagenous spherulosis in a schwannoma. Routine histologic sections
      showed a circumscribed tumor in which the predominant feature was radiating
      fibrillar structures that tended to compress the cellular component of the tumor.
      Immunohistochemical studies showed that the cells were positive for glial
      fibrillary acidic protein (GFAP) and S-100 protein but negative for keratin. EMA
      showed a positive reaction in a thin band of cells around the periphery of the
      tumor consistent with perineurial cells. Type IV collagen stained around the
      periphery of the collagen formations. Electron microscopy revealed that the
      material was consistent with collagen. Our findings were essentially identical to
      those reported in the chondroid syringoma. This case confirms the findings of the
      previous study and shows that these unusual formations are not confined to tumors
      of epithelial origin. Because the architecture of the tumor is distorted, special
      stains may be required for correct diagnosis.

PMID- 7528481
TI  - [Ataxia telangiectasia. Clinical and biological study in 17 cases].
AB  - Seventeen cases of ataxia telangiectasia (AT) were diagnosed over a period of 10
      years. The children affected by AT were aged about 7 years and they were
      preferentially males (67%). The principal clinical aspects were: cerebellous
      ataxia (98%), recurrent ENT infections (86%) and ocular telangiectasia (96%). We
      also showed an immune function defect mainly concerning IgA, which was associated
      with cellular immunity abnormalities (lymphopenia, negative hypersensitivity
      reactions). The alpha-fetoprotein (AFP) values were high and increased in
      proportion to the severity of the neurologic manifestations. Thus, this parameter
      could be used as a diagnostic index of the illness and could be a precious
      indicator for the management and the evolution of these patients.

PMID- 7528480
TI  - [Current principles of the clinical use of central-action analgesics].
AB  - The author analyzes the results of experimental and clinical studies of various
      central action analgesics used for total anesthesia, postoperative analgesia, and
      chronic pain relief in cancer patients. General shortcomings of all opioid
      analgesics were revealed: analgesias not always full-value because of different
      individual sensitivity to opioids, and side effects were often serious. The
      latest progress of the fundamental sciences in research of the mechanisms of pain
      and body responses related to pain helped improve the available and develop new
      more effective methods for total anesthesia and postoperative analgesia on the
      basis of opioid analgesics with the use of special nonopiate components
      compensating for the defects of opiate analgesia: clofelin, an adreno-positive
      agent; acelysin and contrykal, prostaglandin and kinin synthesis inhibitors.
      Synthetic opioids of the latest generation (buprenorphine, tramadol) were found
      preferable in the treatment of chronic pain in cancer vs. morphine and its
      analogs; an alternative scheme of drug therapy of chronic pain on the basis of
      these drugs is offered which is highly effective and causes the minimal side
      effects.

PMID- 7528482
TI  - [Separation of hemoglobins F, Fac, S, C, A1c and determination of hemoglobin F
      using high performance liquid chromatography].
AB  - Separation of hemoglobins F, Fac, S, C and A1c was performed using high
      performance liquid chromatography with a cation exchange Polycat A column in a 15
      minute assay. HbF titration results were well correlated with those of the
      reference alkali denaturation technique for values below 12% (r = 0.95; P <
      0.001). This technique may be used as a confirmation test for neonatal screening
      of sickle cell disease.

PMID- 7528484
TI  - [Theoretical aspects of the treatment with antithyroid drugs].
AB  - Antithyroid drugs (thionamides such as carbimazole and its active metabolite
      methimazole, and propyl thiouracile) are taken up by the thyroid gland just as
      the other anions similar to iodide (perchlorate, thiocyanate, pertechnetate).
      Their target is the thyroid peroxidase. They block the iodation of tyrosine
      residues and the coupling of iodotyrosines into iodothyronines. However, beyond
      the inhibition of thyroid hormone synthesis, antithyroid drugs appear to have the
      capacity of interfering with the immunological abnormalities involved in Graves'
      hyperthyroidism: they cure 50% of the patients provided they are maintained for
      at least 12 months and they significantly decrease the titers of antithyroid
      antibodies in most of the patients. Potential immunomodulatory effects of
      antithyroid drugs seem to involve thyroid depletion of iodine which might reduce
      antigen expression, and scavenging of reactive free radicals generated from
      oxygen and/or iodide during peroxidation. A direct toxic effect of thionamides on
      immuno-competent cells seems unlikely. Whatever the mechanisms, more accurate
      elucidation of the immunomodulatory action of antithyroid drugs might contribute
      to a better understanding of the thyroid-immune derangements involved in the
      initiation or perpetuation of Graves' hyperthyroidism.

PMID- 7528483
TI  - Use of urinary gram stain for detection of urinary tract infection in infants.
AB  - STUDY OBJECTIVE: To determine whether Gram stain of urine is more sensitive than
      urinalysis in detecting urinary tract infection in infants. DESIGN: Prospective
      series. SETTING: Urban teaching hospital emergency department. PARTICIPANTS: Two
      hundred seven infants 6 months old or less, from whom a catheterized or
      suprapubically aspirated urine specimen was obtained for culture. INTERVENTIONS:
      Urinary Gram stain, culture, and urinalysis were performed. With culture results
      as the validating standard, the Gram stain sensitivity, specificity, and
      predictive values were compared with urinalysis, including leukocyte esterase,
      nitrite, pyuria, and bacteriuria. RESULTS: The prevalence of positive cultures
      was 8.7% (18 of 207). Gram stain had higher sensitivity than overall urinalysis
      (94% versus 67%, P < .05), higher specificity (92% versus 79%, P < .05), and
      higher positive predictive value (53% versus 23%, P < .05). CONCLUSION: Urinary
      Gram stain appears to be more reliable than urinalysis in detecting urinary tract
      infection in young infants.

PMID- 7528486
TI  - [Are there prognostic markers of recovery after antithyroid drugs?].
AB  - Sustained remission can be observed among 30-50% of the patients long-term
      treated with antithyroid drugs for Graves' disease. Many parameters have been
      proposed as predictors of remission of relapse of hyperthyroidism. Initial
      thyroid volume and its evolution during therapy, T3/T4 ratio, TSH to TRH
      responsiveness, serum thyroglobulin concentration, and Technetium or Iodine
      uptake under T3 appeared as the most sensitive indicators of intensity or
      permanence of thyroid stimulation activity. Few studies only demonstrated a
      relation between prognosis and HLA B8 or DR3. Those markers predict more
      accurately the relapse than the remission. Their interest and their management in
      clinical practice remain still imperfectly determinated.

PMID- 7528485
TI  - [Treatment of Basedow disease with synthetic antithyroid drugs. Evaluation of the
      dose on the efficacy of the long term treatment].
AB  - A direct immunosuppressive action of antithyroid drugs (ATD) has been suggested
      by the progressive decrease of thyroid antibodies during treatment. High doses of
      ATD were then proposed to improve the level of remissions of Graves' disease but
      the results of such high doses remain a matter of controversies. The french Group
      of Research on Thyroid (GRT) underwent a multicenter study comparing the efficacy
      of 60 mg/d of carbimazole with the minimal dose required to obtain euthyroidism
      in 197 randomly and equally distributed patients. After 18 months of therapy and
      a 2-year follow-up the remissions are 70.9% with high and 53% with low doses (p =
      0.03). After the third year of follow-up, this difference was not significative
      (p = 0.06). Moreover after a 3-year follow-up the remission rate of high dose
      (60.3%) is not different from which is obtained with intermediate one (20 to 30
      mg/d) associated with a permanent decrease of TSH by thyroid hormone.

PMID- 7528487
TI  - [Agranulocytosis induced by synthetic antithyroid drugs: efficacy of
      hematopoietic growth factors].
AB  - Agranulocytosis is the most serious problem, potentially fatal, that can occur
      during antithyroid drug therapy. The use of hematopoietic growth factors is an
      attractive approach to reduce the period of this drug-induced neutropenia. We
      report two cases of severe antithyroid drug-related agranulocytosis (granulocyte
      count < 0.1 x 10(9)/L) treated with Granulocyte Colony-Stimulating Factor (G-CSF)
      or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF). The delay to
      observe a granulocyte count superior to 1 x 10(9)/L was respectively 1 and 5
      days. Our results, with others, clearly show that hematopoietic growth factors
      are effective in severe antithyroid drug-induced agranulocytosis.

PMID- 7528488
TI  - [Treatment of Basedow disease with synthetic antithyroid drugs. Evaluation of the
      effect of the duration of medical treatment on its long term efficacy].
AB  - The modalities of Graves' disease by antithyroid drugs are controversial. In
      particular, the duration of treatment is of great interest. Physicians managing
      Graves' disease patients have used variable periods of treatment. Some have
      proposed a few month short time therapy while others recommend an average of two
      years; others physicians did not used fixed periods but propose various criteria
      for the follow up (TSH us, early iodine uptake, TSAb, TBIAB); the treatment being
      stopped when these markers normalized. The present analysis clearly suggests that
      long term treatment (eighteen months) improves the prognosis of the disease and
      that longer therapeutic periods are not necessary. For the future we have to
      identify the best remittance markers, the aim being to propose drug withdrawal
      according to the individual evolution of these markers.

PMID- 7528489
TI  - [CMDBS, functional analogs of sulfate heparanes, used as osseous cicatrizing
      agents].
AB  - Several Heparin-Binding Growth Factors (HBGFs) are known to play an important
      role in bone repair. When osseous tissue is injured, an important increase of
      protease activities and a massive release of HBGFs occur. The local increase in
      HBGFs content at the wounded site, produced by a release of this factors from
      cells implicated in haemostasis and inflammatory reaction and from extracellular
      matrix associated heparan sulfate proteoglycans (HSPGs), seems to be a crucial
      step in bone healing. The proteolysis associated with the tissue injury probably
      limits the growth factors activities at the wound site. In order to define the
      bone healing potential of molecules that would be able to protect HBGFs against
      proteolytic activation, we studied the effect of derived dextrans, named
      carboxymethyl-benzylamide-sulfonated dextrans (CMDBS), behaving as heparan like
      molecules, in 5 mm in diameter skull trepaned defects in young adult rats. In
      this model CMDBS induced an important bone regeneration in a dose dependent
      manner while controls were not repaired. In CMDBS treated animals the defects
      were repaired and contained a tissue of normal appearance; in several treated
      animals the sagittal suture, initially removed by the trephination, was restored.
      This remarkable bone healing potential of CMDBS may result from the capacity to
      protect the endogenous HBGFs from proteolysis and to modulate their biological
      activities, in a similar manner to that observed for fibroblast growth factors
      and HSPGs. CMDBS represent a new form of bone healing agents, which have the
      advantage of being produced by a controlled chemical synthesis, and of avoiding
      the use of exogenous growth factors because of their capacity to enhance the bone
      healing potential of the endogenous growth factors.

PMID- 7528490
TI  - [The importance of pain control with morphine for terminally ill patient care for
      at home].
AB  - From April 1987 to June 1994, 81 patients of terminally ill had been care at
      home. In these home care, 38 patients received pain control with morphine. In 29
      patients, pain control had been started before home care but in 9 patients pain
      control had been started under home care. Routes of morphine administration were
      oral in 24 cases and rectal in 14 cases. In cases of oral routes, finally 2 cases
      converted to rectal routes and 2 cases converted to subcutaneous routes. Duration
      of treatment were from 2 days to 741 days (average 72 days). Dosage of morphine
      were 7.5 mg to 480 mg (average 116 mg). Two patients lived but 24 patients died
      at home and 12 patients died at hospital. We concluded that palliative care
      especially pain control with morphine was very important care for patients of
      terminally ill who wanted care at home and ultimately die at home. We had to make
      ourself master of method pain control with morphine.

PMID- 7528491
TI  - [Current status and problems of home care for patients with terminal cancer from
      the viewpoint of local clinics].
AB  - On the basis of investigations of 15 patients from our clinic with terminal
      cancer who were treated by home hospice care, and questionnaires filled out by
      their caretakers, we examined the current status and problems of the home hospice
      care system with respect to four phases, namely, the period of preparation for
      home care (hospitalization period), stable period, terminal period, and the
      period immediately before death. [Preparation period] The following problems
      occurred in this phase: introduction of pain management and nutrition management
      was insufficient; there were only a few cases in which the patient chose home
      care of his or her own will; and sufficient instructions were not given to
      caretakers on discharge from the hospital, with respect to medical treatment at
      home. [Stable period] In two of the four cases in which patients complained of
      severe pain, the pain was not alleviated because pain management was provided
      only at the outpatient clinics of the hospital, and collaboration between
      hospitals and our clinic was insufficient. [Terminal period] Two patients could
      not be admitted to the hospital upon sudden exacerbation of the condition,
      suggesting the need to establish a system in which large hospitals can cope with
      sudden exacerbation of their condition of patients with terminal cancer treated
      at home. [Period immediately before death] Of the 14 patients who died, 7 died at
      home and 7 died in the hospital or during transport to the hospital. Three
      subjects died within a few days after admission. Two of the subjects who died in
      the hospital or during transport had hoped to stay home until the last moment.
      Further improvement of the system is necessary in order to meet the needs of
      terminal cancer patients who wish to die at home. On the basis of the cases taken
      care of at our clinic, we examined the home care system according classification
      into three types; hospital-outpatient clinic type; hospital-home care type; and
      clinic-home care type. An ideal system for the treatment of patients with
      terminal cancer who hope to stay at home until the last possible moment seems to
      be the clinic-home care type in which a primary care team that is able to
      dispatch physicians and nurses, and an around-the-clock support system, are
      supported by outside organizations and specialists.

PMID- 7528492
TI  - [Problems and solutions of home care for a terminal cancer patient--cooperation
      as a team approach].
AB  - In order to have a terminal cancer patient spending fulfilling remaining of his
      life, the role of home care is important. Caremark clinical team, consists of
      nurses, pharmacists and clinical coordinators (CC), provides home care service
      for patients. We have faced many problems regarding providing care for our cancer
      patients, especially terminal patients, and solved the problems in cooperation
      with the physicians. The main problems which we have faced with care for terminal
      cancer patients are as follows: (1) For emergency case, such as sudden changes in
      patient condition, if a hospital where the patient used to stay can not accept
      his return, our clinical coordinator makes a contact with closer hospital and
      asks them to hospitalize the patient. (2) Concerns of a patient and his family
      increase when his pain is getting severe. For this case, our nurse gives his
      caregiver training on treatment method, and normal pain management care for the
      patient. Also our pharmacist talks with the patient and his family and try to
      reduce the pain by using more suitable drugs at each conditions. (3) A patient
      with serious conditions which requires long term home care, his family and
      caregivers have more burdens. For this problem we suggests them to use high touch
      home care providers, and also our nurse provides psychological care (counseling).
      We have solved other problems in cooperation with each specialists, and we are
      confident that we are able to provide better home care service for our patients.

PMID- 7528493
TI  - [Home therapy approach in cancer patients--pain control (case 3-1)].
AB  - We present a case study of 34 years old female patient who had intractable pain
      in terminal stage of lung cancer. She complained severe persistent shooting pain
      in left lateral pectoral region, where was a wound of thoracotomy. She was given
      several analgesics orally in order of their efficacy, but could not get
      sufficient pain relief. From the nature of the pain that she had, neurological
      findings, and the result of thermography examination, we decided that the pain
      was associated with the failure of sympathetic nervous system. Then, she was
      admitted to our hospital and received the thoracic epidural block after epidural
      catheterization. But she could not get continuous pain relief. For the purpose of
      her return to the home therapy, we tried to administer MS Contin to her.
      Subsequently, she took a turn for the worse and died due to respiratory
      dysfunction in our hospital in the middle of her pain treatment.

PMID- 7528494
TI  - [Home therapy approach in cancer patients--pain control (case 3-3)].

PMID- 7528495
TI  - [Involvement of epidermal growth factor receptor (EGFR) in the etiopathogenesis
      of prostatic proliferative processes].
AB  - The prostatic growth factors require a membrane specific receptor to which they
      must bind in order to carry out their biological activities correctly. The aim of
      this study was to isolate and quantify the epidermal growth factor receptor in
      prostatic tissue and indirectly determine the growth factors acting on it (EGF,
      TGF alpha, PDGF, NGF, IGF). From September, 1992 to June, 1993, we studied 55
      patients. These were divided into two groups: the first group comprised 49
      patients with benign prostatic hyperplasia (BPH) and 6 patients with prostatic
      carcinoma comprised the second group. Samples of the prostate were obtained
      following suprapubic (12 cases), TUR (38 cases), radical prostatectomy (1 case)
      and transrectal biopsy (4 cases). The EGFR was determined by radioimmunoassay
      (EGFR-RIA, Vienna Lab, Labordiagnostica GmbH). For the overall group of patients,
      we obtained mean EGFR values of 6.36 +/- 0.59 fmol/mg of protein and a positivity
      of 96.36% and 100% for BPH and malignant proliferative processes, respectively.
      The foregoing data show that EGFR was isolated from the tissue we analyzed and
      has an evident role in the regulation of prostate growth.

PMID- 7528497
TI  - Involvement of substance P but not nitric oxide or calcitonin gene-related
      peptide in neurogenic plasma extravasation in rat incisor pulp and lip.
AB  - The possible involvement of the neuropeptides substance P and calcitonin gene
      related peptide (CGRP) in the development of neurogenic plasma extravasation in
      the lower lip, gingiva and incisor pulp was examined in anaesthetized rats by
      means of the Evans blue method and by using newly developed blockers of substance
      P (CP-96,345) and CGRP (CGRP8-37). Electrical stimulation of the inferior
      alveolar nerve (15 V, 2 ms, 10 Hz) for 5 min significantly increased the Evans
      blue content of the ipsilateral lip, gingiva and pulp by 60 (p < 0.01), 62 (p <
      0.01) and 92% (p < 0.05), respectively (n = 8). Pretreatment with CP-96,345
      (total dose: 1.5 mg/kg, intravenously) counteracted the dye leakage in the lip
      and pulp but not in the gingiva (n = 6). The inactive enantiomer (CP-96,344, 1.5
      mg/kg, n = 8) or the nitric oxide synthesis inhibitor (N omega-nitro-L-arginine
      methyl ester hydrochloride, 10 mg/kg, n = 7) did not reduce the stimulation
      induced dye extravasation in any of the tissues. Pretreatment with CGRP8-37 (0.3
      mg/kg, n = 7) did not significantly influence the development of neurogenic
      extravasation in the lip and incisor pulp, but it slightly attenuated
      extravasation in the gingiva. The results indicate that the afferent nerve
      induced dye extravasation in the lip and pulp, but not in the gingiva, is to a
      large extent mediated by substance P acting via neurokinin-1 receptors. There was
      no evidence for an involvement of nitric oxide or CGRP in neurogenic
      extravasation in rat incisor and lip.

PMID- 7528496
TI  - Effects of cyclosporine and tacrolimus (FK 506) on acute pancreatitis in mice.
AB  - OBJECTIVE: To use mice to examine the effects of cyclosporine and tacrolimus (FK
      506) on two forms of acute pancreatitis often seen after clinical organ
      transplantation. METHODS AND DESIGN: In the first experiment, male CD-1 mice
      received cyclosporine (10 mg/kg), tacrolimus (0.32 mg/kg), or saline solution
      (control) subcutaneously once a day for 10 days. On the 11th day, acute edematous
      pancreatitis was induced by ceruletide (cerulein). In the second experiment,
      female ICR mice were fed with a choline-deficient, ethionine-supplemented (CDE)
      diet for 72 hours to induce necrotizing pancreatitis. After 30 hours on the CDE
      diet, the mice received cyclosporine (10 mg/kg), tacrolimus (0.32 mg/kg), or
      saline solution (control) subcutaneously twice daily for 3 days. RESULTS: The
      pancreatic dry-to-wet weight ratios after ceruletide injections significantly
      decreased in mice treated with cyclosporine but did not with tacrolimus.
      Cyclosporine also significantly increased serum amylase levels, but tacrolimus
      did not. Cyclosporine or tacrolimus alone did not produce pancreatitis. In the
      CDE diet groups there was a significant difference in survival among the
      cyclosporine-treated, the tacrolimus-treated, and the control groups.
      CONCLUSIONS: Cyclosporine or tacrolimus given alone does not induce acute
      pancreatitis. In contrast, cyclosporine can adversely affect the course of acute
      edematous pancreatitis, and both immunosuppressants may worsen the survival of
      mice with acute hemorrhagic necrotizing pancreatitis. This study also
      demonstrated that the deteriorating effect of tacrolimus is less potent than that
      of cyclosporine.

PMID- 7528498
TI  - Tyrosine kinase specific motif at subdomain VIII does not confer specificity for
      tyrosine.
AB  - The majority of protein kinases fall within one of the two broad classes, kinases
      that phosphorylate serine or threonine and kinases that phosphorylate tyrosine.
      The structural basis that confers residue specificity is not known. However, it
      has been hypothesized that a region in subdomain VIII of the catalytic domain may
      be involved in determining kinase specificity. This region contains a motif which
      is conserved among serine/threonine kinases and different from the one conserved
      among tyrosine kinases. We have prepared a chimera of the tyrosine kinase pp56lck
      in which the tyrosine kinase motif at subdomain VIII has been exchanged for the
      corresponding region of the serine/threonine kinase c-Raf. Our results indicate
      that this motif itself does not confer amino acid specificity since the chimeric
      kinase still displays specificity for tyrosine.

PMID- 7528499
TI  - Oscillations of cytosolic calcium in rat chromaffin cells: dual modulation in
      frequency and amplitude.
AB  - Rat chromaffin cells in primary culture have a high tendency to exhibit [Ca2+]i
      oscillations, spontaneously or after moderate stimulation with treatments that
      induce polyphosphoinositide hydrolysis or mild depolarization. Previous studies
      in a variety of cell systems had shown that strengthening of the above treatments
      increases the frequency and not the amplitude of the oscillations. We now
      demonstrate that in cultured chromaffin cells either one of these oscillation
      reinforcements can be elicited, depending on whether the Ca2+ influx induced by
      the applied stimulus is asynchronous with or timed by the [Ca2+]i spikes of the
      oscillations. In excitable cells the encoding of the oscillation activity appears
      therefore to operate according to not only digital (modulation in frequency) but
      also analog (modulation in amplitude) models.

PMID- 7528500
TI  - Structural basis of SH2 domain mutations in X-linked agammaglobulinemia.
AB  - The three-dimensional structure of Bruton's agammaglobulinemia tyrosine kinase
      (Btk) SH2 domain was modeled based on v-Src. Btk SH2 is presumably very related
      to the other SH2 structures consisting of two beta-sheets surrounded by two alpha
      helices, with a well conserved hydrophobic core and phoshotyrosyl peptide binding
      site. The model was used to predict the recognition sequence of the target
      protein, which probably is YEXI/L. Mutations in the Btk sequence can cause the
      human disease X-linked agammaglobulinemia and reasons for the disease in Btk SH2
      mutations were inferred from the model.

PMID- 7528502
TI  - Detection of elevated basic fibroblast growth factor during early hours of in
      vitro angiogenesis using a fast ELISA immunoassay.
AB  - Basic FGF (bFGF) is a growth factor that is thought to play an important role in
      angiogenesis. Available assays that are used to detect bFGF are long and
      cumbersome. Here, we present a fast, easy and sensitive sandwich-type enzyme
      immunoassay for bFGF detection. Our method is a modification of the method
      described by Watanabe et al (Biochem. Biophys. Res. Commun. 1991; 175, 229). Two
      monoclonal antibodies for antigen capture and one noncongugated polyclonal
      antibody for antigen detection are used instead of using three monoclonal
      antibodies with the congugation of one of them for detection. There is no change
      in the sensitivity of the assay with average detection limit of 1 pg/well. Acidic
      fibroblast growth factor does not interfere with the assay. Using this method,
      samples from conditioned media of capillary endothelial cell culture before and
      after angiogenesis were measured. Associated with detection of start of tube
      formation, basic FGF was elevated at 8 hours from angiogenic stimulation and
      peaked at 48 hour (4 times control), showing for the first time in an in vitro
      system that there is a transient increase in endogenous bFGF accompanying early
      steps of angiogenesis which in turn may be the trigger for new capillary
      formation.

PMID- 7528503
TI  - Quantitative RT-PCR assay detecting the transcriptional induction of vascular
      endothelial growth factor under hypoxia.
AB  - Quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay was
      used to examine the induction of vascular endothelial growth factor (VEGF)
      transcript in human osteosarcoma cells, MG-63, under hypoxic culture condition.
      Using this assay system, the expression of VEGF mRNA was estimated eight-fold
      higher when cells were cultured under hypoxic condition. Transcription level of
      hypoxanthine phosphoribosyl transferase (HPRT) mRNA was also examined as an
      internal control. HPRT mRNA level under hypoxia was reduced to one fourteenth.
      Secretion of VEGF into the cell culture medium was implied by its stimulating
      activity on the growth of mouse vascular endothelial cultured cells in vitro.

PMID- 7528504
TI  - Forskolin and methylxanthines block the increase in intracellular pH during
      meiosis in Xenopus laevis oocytes.
AB  - Xenopus oocytes, arrested in late prophase of the meiotic cell cycle, undergo
      nuclear membrane breakdown (Germinal Vesicle Breakdown, GVBD) in response to
      progesterone stimulation. During this prophase/M-phase transition the oocytes
      undergo an increase in their intracellular pH (pHi) from 7.3 to 7.7 in response
      to the steroid. This increase in pHi appears to be due to the activation of
      Na+/H+ antiporters in the oocyte plasma membrane. Several studies have shown that
      the pathway leading to GVBD is blocked by forskolin or methylxanthines which
      elevate cAMP levels within the oocyte. We have found that these same compounds
      also blocked the up-regulation of the Na+/H+ exchangers during oocyte meiotic
      maturation.

PMID- 7528501
TI  - Seven transmembrane domain receptor subtypes identified in NG108-15 cells by
      reverse transcription-polymerase chain reaction.
AB  - NG108-15 neuroblastoma x glioma cells are widely used for the study of
      neurotransmitter receptors. We utilized reverse transcription-polymerase chain
      reaction to amplify members of the seven transmembrane domain class of G-protein
      linked receptors using RNA isolated from NG108-15 cells. Two complementary DNAs
      representing receptors were obtained; based upon comparison with the sequence
      database, they probably represent the murine dopamine D1A receptor and a receptor
      closely related to the serotonin 5HT1D receptor subtype. The finding of the 5HT
      receptor subtype is of interest, as only the 5HT3 subtype was previously
      identified in NG108-15 cells by pharmacological means. Certain responses of NG108
      15 cells to serotonin have been described that do not appear to be mediated by
      known 5HT receptor subtypes. The cDNA we cloned may therefore represent an
      additional 5HT1D subclass.

PMID- 7528505
TI  - Glycosylphosphatidylinositol toxin of Trypanosoma brucei regulates IL-1 alpha and
      TNF-alpha expression in macrophages by protein tyrosine kinase mediated signal
      transduction.
AB  - A purified, structurally defined glycosylphosphatidylinositol (GPI) derived from
      the Variant Surface Glycoprotein (VSG) of Trypanosoma brucei, and its
      biosynthetic precursor P2, was able at submicromolar concentrations to regulate
      cytokine expression when added directly as pharmacological agonist to host
      macrophages, by activation of an endogenous protein tyrosine-kinase (PTK)
      mediated signal transduction pathway. GPI induces rapid onset tyrosine
      phosphorylation of multiple intracellular substrates, within minutes of addition
      to LPS-nonresponsive cells, followed shortly thereafter by IL-1 alpha secretion.
      The PTK antagonists genistein and tyrphostin inhibit both tyrosylphosphorylation
      and cytokine expression. A monoclonal antibody to GPI also blocks IL-1 alpha
      induction by total parasite extracts. Thus, as in malaria infection, GPI may
      induce the cytokine excess causing certain pathological states associated with
      trypanosomiasis.

PMID- 7528507
TI  - Cytotoxicity and metabolism of 4-methoxy-8-(beta-D
      ribofuranosylamino)pyrimido[5,4-d]pyrimidine in HCT 116 colon cancer cells.
AB  - We examined the cytotoxicity, biochemical effects and metabolism of 4-methoxy-8
      (beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (MRPP), a synthetic
      nucleoside inhibitor of phosphoribosylpyrophosphate synthetase, in HCT 116 human
      colorectal cancer cells. A 4-hr exposure to 1 and 10 microM MRPP inhibited cell
      growth over a 72-hr period by 76 and 89%, and inhibited clonogenic capacity by 36
      and 65%, respectively. MRPP was avidly metabolized to the 5'-monophosphate
      derivative (MRPP-MP), and MRPP-MP formation increased with increasing MRPP
      exposure (microM.hr). MRPP-MP was stable, and the intracellular half-life was in
      excess of 48 hr. A 4-hr exposure to 10 microM MRPP resulted in significant
      decreases in ATP, UTP, GTP, CTP, dATP, dTTP, and PRPP pools. Near maximal
      ribonucleotide triphosphate depletion was achieved with > or = 24 microM.hr MRPP,
      and growth inhibition as a function of MRPP microM.hr closely reflected the
      biochemical effects. Ribonucleotide triphosphate pools remained depleted for up
      to 48 hr after drug removal, apparently as a consequence of the prolonged
      retention of MRPP-MP. MRPP (10 microM) inhibited the salvage of [3H]guanine,
      [3H]adenine and [3H]guanosine, and concurrent exposure to MRPP and either 100
      microM adenine, hypoxanthine, or guanine did not reverse ATP or GTP depletion.
      Concurrent exposure to 10 microM MRPP and either 10 microM adenosine, uridine or
      thymidine was accompanied by repletion of ATP, UTP, and dTTP pools, respectively,
      but depletion of other nucleotide pools was not corrected. In contrast, 10 microM
      guanosine did not correct GTP depletion in the presence of MRPP. The combination
      of 10 microM each of thymidine, uridine, adenosine and guanosine during and
      following a 24-hr exposure to MRPP provided partial protection against 0.1 or 1
      microM MRPP, but did not affect the cytotoxicity associated with 10 microM MRPP.
      MRPP is a novel antimetabolite that inhibits both de novo and salvage pathways
      for purine synthesis and de novo pyrimidine synthesis.

PMID- 7528506
TI  - Chronotropic effects of cytokines and the nitric oxide synthase inhibitor, L
      NMMA, on cardiac myocytes.
AB  - We and others have proposed that cytokine-stimulated nitric oxide (NO) production
      is responsible for reversible myocardial depression in sepsis, trauma and
      ischemia. An effect of NO on cardiac sarcolemmal L-type calcium channels has also
      recently been proposed. The spontaneous beating rate of neonatal cardiac myocytes
      is regulated by the sarcolemmal L-type calcium channel. Accordingly, we sought to
      determine if cytokine-stimulated NO production could also regulate beating rates
      of neonatal cardiac myocytes. Treatment of neonatal rat cardiac myocytes with
      TNF, IL-1, IL-6, 10(-5)M NMA, or 10(-3)M NMA significantly enhanced spontaneous
      beating rates compared to untreated myocytes in serum-free media for 48 hours (p
      < or = .01; n = 12 for each). Only IL-1 treatment resulted in significant nitrite
      levels vs. control over 48 hours (4.2 +/- 0.7 vs. 0.3 +/- 0.2 nmoles/1.25 x 10(
      5) cells, respectively) (n = 12). Nitrite production by IL-1 was inhibited by 10(
      3)M NMA but not 10(-5)M NMA (0.3 +/- 0.2 vs. 4.1 +/- 0.6 nmoles; p < .01; n =
      12). The addition of 10(-5)M NMA to TNF, IL-1, and IL-6 did not alter the effect
      of the cytokines on the spontaneous beating rates of the cardiac cells (p < or =
      .01; n = 12 for each). These results strongly suggest that cytokines and NMA
      affect cardiac myocyte spontaneous beating rates through mechanisms independent
      of NO.

PMID- 7528508
TI  - [Manifestation of Urbach-Wiethe syndrome in the ENT area].
AB  - Urbach-Wiethe's syndrome (hyalinosis cutis et mucosae) is a rare genetic defect
      of probably autosomal recessive origin. The exact nature concerning the
      pathogenesis of this disorder is still controversial. A characteristic symptom in
      early childhood might bei hoarseness, later on manifestations with hyalin
      deposits in the larynx, oral cavity and oropharynx might occur as well as
      yellowish-white papular deposits in the skin. The overall prognosis of this
      disease is good, therapeutic intervention might be necessary for functional
      purposes (narrowing of the laryngeal lumen) and consists of surgical removal of
      the lesions.

PMID- 7528509
TI  - [Burden of DDT, HCH, HCB and PCB in human milk in the former German Democratic
      Republic. Research and toxicologic evaluation].
AB  - The decreasing tendency of the contamination of human milk with residues of
      organochlorine compounds (DDT, HCH, HCB, PCB) has been confirmed by our
      investigations also for the territory of the former GDR. Compared with the
      residue-situation existing in the FRG, the contamination of breast milk with DDT
      metabolites 4,4'-DDE and 4,4'-DDT were elevated. A positive correlation was found
      between age and HCB-exposure, urban residency and 4,4'-DDE, beta-HCH and PCB, and
      smoking and beta-HCH-residues in human milk.

PMID- 7528510
TI  - [Latex and pollinosis].
AB  - Through the multidetection test for specific IgE to pneumoallergens (Aero-Matrix
      Plus, Abbott) our attention has been drawn to polysensitization to pollens.
      Amongst these pollen tests, plantain seems to be frequently associated with
      sensitization to latex. The aim of this work at first, is therefore to verify the
      reality of the frequency of the association between latex and plantain
      sensitization. However, the conclusions are difficult, since there are no
      patients who are only sensitive to plantain as sensitivity to this allergen is
      always found in a pollen polysensitization. at least associated with grass
      pollens; at most associated with a number of other pollens. The double profile
      (perhaps plantain + / grass pollen +, or perhaps plantain + / grass pollen + /
      other pollens +) is determinant in prediction of sensitivity to latex, which is
      found essentially in the group plantain + / grass pollen + / other pollens +.
      This study has also shown that amongst the population who have specific IgE to
      latex (IgEs) (sensitized or allergic): the patients who have a clinical history
      of allergy to latex have no profile of pollen polysensitization; the non-allergic
      but sensitive patients (IgE positive, but no clinical signs on contact with
      latex) show an extreme pollen polysensitization. This poses a problem of
      different antigenic determinants or perhaps two different pathways to
      sensitization to latex.

PMID- 7528511
TI  - Quantitative and qualitative aspects on the distribution of 5-HT and its
      coexistence with substance P and TRH in cat ventral medullary neurons.
AB  - By use of the indirect immunofluorescence technique the distributions of 5
      hydroxytryptamine (5-HT)-, substance P- and thyrotropin-releasing hormone (TRH)
      immunoreactive (IR) neurons have been studied in the midline raphe nuclei and
      nucleus reticularis lateralis of the caudal brainstem (levels P18.3-P8.5;
      according to Berman (1968), in the cat, after treatment with colchicine. In
      addition, by use of the double-labelling technique, the coexistence between 5-HT
      , substance P- and TRH-like immunoreactivity (LI) in these neurons was analysed.
      The results show that cell bodies in the midline raphe nuclei and nucleus
      reticularis lateralis contain 5-HT-, substance P- and TRH-LI. 5-HT-IR cells were
      more abundant than peptidergic neurons in all areas analysed. Quantitative
      estimations indicated that the total number of 5-HT-IR cells in the regions
      studied was about 17 x 10(3), while the corresponding numbers for substance P-
      and TRH-IR cells were 11 x 10(3) and 12 x 10(3), respectively. From double
      labelled sections it was concluded that the vast majority of peptidergic cells
      also contained 5-HT-LI (87-100%). However, a subpopulation of 5-HT-IR neurons
      lacked peptide-LI (10-55%). The degree of coexistence varied with the brainstem
      level, in that neurons at more rostral locations showed a lower incidence of
      coexistence between 5-HT and peptide(s). The presence of all three compounds in
      one and the same cell body could also be demonstrated. In summary, 5-HT-,
      substance P- and TRH-IR cell bodies were encountered in medullary nuclei known to
      contain neurons with projection to the spinal cord. A high degree of coexistence
      between the compounds was demonstrated in these nuclei. The obtained results fit
      well with earlier studies on the patterns of distribution and peptide
      colocalization of 5-HT fibres in the spinal cord. The existence of biochemically
      distinct neuronal subpopulations within the 5-HT bulbospinal pathway is
      discussed.

PMID- 7528512
TI  - Serotoninergic, peptidergic and GABAergic innervation of the ventrolateral and
      dorsolateral motor nuclei in the cat S1/S2 segments: an immunofluorescence study.
AB  - Indirect single- and double-staining immunofluorescence techniques were used to
      study the serotoninergic, peptidergic and GABAergic innervation of the
      ventrolateral (Onuf's nucleus) and dorsolateral (innervating intrinsic foot sole
      muscles) nuclei, located in the S1/S2 segments of the cat spinal cord. The
      relative density of 5-hydroxytryptamine-, thyrotropin-releasing hormone-,
      substance P- and gamma-aminobutyric acid-immunoreactive axonal varicosities was
      similar in both nuclei. The highest relative density was recorded for
      varicosities immunoreactive to gamma-aminobutyric acid, while those
      immunoreactive to 5-hydroxytryptamine or thyrotropin-releasing hormone yielded
      the lowest values. The density of enkephalin-immunoreactive varicosities was
      higher in the ventrolateral than in the dorsolateral nucleus. Calcitonin gene
      related peptide-like immunoreactivity could be seen in neurons of the
      ventrolateral and dorsolateral nuclei. Occasionally, calcitonin gene-related
      peptide-immunoreactive axonal fibers were also encountered in these nuclei.
      Virtually all thyrotropin-releasing hormone-immunoreactive varicosities in the
      ventrolateral and dorsolateral nuclei also contained 5-hydroxytryptamine-like
      immunoreactivity, while a somewhat smaller number of them were co-localized with
      substance P. About 5-10% of the 5-hydroxytryptamine-immunoreactive varicosities
      were devoid of peptide-like immunoreactivity, and the number of 5
      hydroxytryptamine-immunoreactive varicosities lacking thyrotropin-releasing
      hormone-like immunoreactivity was higher in the dorsolateral than in the
      ventrolateral nucleus. Finally, the free fraction of substance P-immunoreactive
      varicosities, i.e., those lacking both 5-hydroxytryptamine and thyrotropin
      releasing hormone, was about 39% in the ventrolateral and 26% in the dorsolateral
      nucleus. Spinal cord transection at the lower thoracic level induced a depletion
      of 5-hydroxytryptamine and thyrotropin-releasing hormone-immunoreactive fibers
      from the ventrolateral and dorsolateral nuclei, indicating an exclusive
      supraspinal origin for these fibers. A reduction in substance P-like
      immunoreactivity following spinal cord transection alone or spinal cord
      transection combined with unilateral dorsal rhizotomy was also detected in both
      nuclei, suggesting a dual origin for substance P-immunoreactive fibers, i.e.,
      both supra- and intraspinal. The decrease in number of substance P-immunoreactive
      fibers was however smaller than expected from the analysis of the fraction of
      substance P-immunoreactive fibers co-localized with 5-hydroxytryptamine,
      indicating thus that the experimental lesions may have triggered a sprouting of
      substance P-immunoreactive axons originating from spinal cord sources. The
      distribution of gamma-aminobutyric acid in the ventrolateral and dorsolateral
      nuclei was not affected by the different lesion paradigms. It is therefore
      assumed that these inputs are intrinsic to the spinal cord.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7528513
TI  - Angiogenic potential in vivo by Kaposi's sarcoma cell-free supernatants and HIV-1
      tat product: inhibition of KS-like lesions by tissue inhibitor of
      metalloproteinase-2.
AB  - OBJECTIVE: To determine the neoplastic nature of Kaposi's sarcoma (KS). A highly
      vascularized lesion, KS is frequently associated with AIDS, indicating HIV
      products may be involved. DESIGN AND METHODS: We determined the angiogenic
      properties of KS cell-secreted products and the HIV-1-tat gene product in vivo.
      Cell-free secreted products (KS-CM) from cultured epidemic and sporadic KS
      spindle cells or recombinant (r) HIV-1 tat protein were injected into mice with a
      matrix support (Matrigel). RESULTS: KS-CM produced lesions carrying all the
      phenotypic hallmarks of KS, as observed by light and electron microscopy: spindle
      shaped cells, haemorrhages and an inflammatory infiltrate, as well as Factor VIII
      positive endothelial cells lining new blood vessels. Electron microscopy
      indicated an initial granulocyte invasion, with spindle-cell migration and
      neocapillary formation in the centre of the matrix. These lesions required the
      cofactor heparin; KS-CM or heparin alone were poorly angiogenic. A less intense
      angiogenesis, with lower cellularity and few granulocytes, was observed in basic
      fibroblast growth factor (bFGF)/heparin lesions, indicating that factors other
      than bFGF are present in the KS spindle-cell products. When the collagenase
      inhibitor tissue inhibitor of metalloproteinases (TIMP)-2 was added to the
      sponges, KS-CM-induced angiogenesis was reduced by approximately 65% and bFGF
      induced angiogenesis inhibited completely. Recombinant HIV-1 tat protein, a
      growth factor for KS cells, induced vascularization that was also enhanced by
      heparin, implying that HIV-1 tat could contribute to the aetiology of HIV
      associated KS. CONCLUSIONS: KS-like lesions were obtained by injecting cell-free
      secreted products, suggesting that KS is a 'self-propagating' proliferative
      lesion caused by a cytokine imbalance and not a true neoplasm. Heparin-binding
      factors appear to be involved, and HIV-1 tat angiogenic properties implicate this
      molecule in AIDS-associated KS. Inhibition of KS-CM-induced KS-like lesions by
      TIMP-2 suggests that metalloproteinase inhibitors could be potential therapeutic
      agents for KS.

PMID- 7528514
TI  - Immunogenicity of the N-glycans of peanut peroxidase.
AB  - The three tryptic glycopeptides of cationic peanut peroxidase (C. PRX) and the
      sole one of anionic peanut peroxidase (A. PRX) were individually coupled to
      bovine serum albumin to raise antisera. The three categories of antibodies
      directed towards three N-glycans of C. PRX (anti-GLa, anti-GLb and anti-GLc) were
      isolated from antisera with glycan-conjugated ECH Sepharose 4B affinity columns
      and the distribution of epitopes on the N-glycans was investigated. The
      reactivity of anti-GLa, anti-GLb and anti-GLc is inhibited 25-40% by 1 M fucose,
      compared with a slight inhibition by N-acetylglycosamine and xylose. Mannose and
      galactose showed no inhibition to anti-GLa and only a slight inhibition to anti
      GLb and anti-GLc. All of anti-GLa, anti-GLb and anti-GLc recognize A. PRX and
      horseradish peroxidase but do not recognize fetuin. Also, their reactivity is
      inhibited by bromelain by more than 70%. The three categories of antibodies
      present high homogeneity and appear to be directed mainly towards the core
      structure [Xyl] (Man)3 [Fuc] (GlcNAc)2. An effective and simple method to screen
      antibodies with carbohydrate specificities is described herein.

PMID- 7528515
TI  - Circulating insulin-like growth factor binding proteins (IGFBPs) 1 and 2 induced
      in vitamin C-deficient or fasted guinea pigs inhibit IGF-I action in cultured
      cells.
AB  - Collagen gene expression and proteoglycan synthesis are decreased in vitamin C
      deficient guinea pigs losing weight and in fasted guinea pigs receiving
      ascorbate. Sera from such guinea pigs contain an insulin-like growth factor (IGF)
      I-reversible inhibitor of collagen, proteoglycan and DNA synthesis and elevated
      levels of 29 and 35-kDa IGF binding proteins (IGFBPs). We now have identified the
      induced proteins as IGFBPs 1 and 2 and investigated their role as inhibitors.
      Guinea pig sera were treated with antibodies to IGFBPs 1 and 2 and antibody-IGFBP
      complexes were removed by passage through a Protein A-Sepharose column. Inhibitor
      content of fasted and scorbutic sera, and Protein A pass-through fractions
      derived from them, was assessed by their level of stimulation of DNA and collagen
      synthesis in 3T3 cells, compared to analogously treated normal guinea pig serum.
      Removal of IGFBP-1 from scorbutic serum reversed inhibition of collagen and DNA
      synthesis by more than half but removal of IGFBP-2 was less effective. Removal of
      both IGFBPs reversed inhibition almost completely. Similar results were obtained
      with fasted guinea pig serum. Conversely, purified rat IGFBPs 1 and 2 inhibited
      DNA and collagen synthesis in cells cultured in normal guinea pig serum or IGF-I
      stimulated DNA synthesis, with IGFBP-1 being more potent. Thus, IGFBP-1 and, to a
      lesser extent IGFBP-2, cause inhibition of IGF-I action by sera from fasted and
      scorbutic guinea pigs and may inhibit collagen gene expression in vivo.

PMID- 7528516
TI  - Colocalization of acidic and basic fibroblast growth factor (FGF) in human
      placenta and the cellular effects of bFGF in trophoblast cell line JEG-3.
AB  - The placenta undergoes extensive angiogenesis and cellular proliferation to
      establish adequate blood supply to the fetus. The aim of this study was to
      compare and contrast the immunolocalization of acidic and basic fibroblast growth
      factor (FGF) in both first trimester and term placenta and gestational decidua.
      Human choriocarcinoma cell line JEG-3 were employed as a model of cytotrophoblast
      and the effect of basic FGF on cell proliferation and phospholipase C and D
      activation investigated. Basic FGF-immunoreactivity (IR) was detected in or
      around cytotrophoblast cells and in extravillous trophoblast in first trimester
      placenta by immunohistochemistry using primary polyclonal rabbit antibodies.
      Identical staining patterns were produced by acidic FGF antibodies indicating
      colocalization of acidic FGF and basic FGF. At term, weaker and more diffuse
      staining was seen in the syncytiotrophoblast surrounding the placenta villi and
      strong staining was present in the smooth muscle cells of mid and large size
      placental vessels and in some endothelial cells. Endothelial cells and
      extravillous trophoblast stained strongly within the decidua at first trimester,
      whereas the glandular epithelium was weakly stained. Basic FGF induced
      [3H]thymidine incorporation in JEG-3 cells in a dose dependent manner and caused
      an increase in inosital phosphate accumulation in cells pre-labelled with myo
      [3H]inosital at similar concentrations, suggesting a role of phospholipase C in
      JEG-3 cell proliferation. However, basic FGF failed to stimulate phospholipase D
      activity in cells pre-labelled with [3H]myristic acid. The detection of acid FGF
      and basic FGF on both maternal and fetal side of the placenta during early
      pregnancy suggests a role for FGF in angiogenesis, whereas localisation of the
      growth factor at term, when extensive angiogenesis has diminished, would indicate
      that FGF may be associated with more differentiated functions of the trophoblast.
      The nuclear localization of basic FGF in dividing but not non-dividing placental
      cells together with the effect of basic FGF on JEF-3 cells, strongly supports a
      role for basic FGF in cytotrophoblast proliferation in vivo.

PMID- 7528517
TI  - Characteristics of FGF-receptors expressed by stromal and epithelial cells
      cultured from normal and hyperplastic prostates.
AB  - Three fibroblast growth factors (FGFs), acidic FGF (FGF1), basic FGF (FGF2), and
      keratinocyte growth factor (FGF7) have been identified in prostate. To understand
      how FGFs regulate growth of the prostate, and to determine if regulation is
      altered in benign prostatic hyperplasia (BPH), the mitogenic potential of FGFs,
      receptor binding, and FGF-receptor (FGFR) gene expression of stromal (PS) and
      epithelial cells (PE) cultured from normal human prostate and BPH where
      determined. FGF1 and FGF2, but not FGF7, were mitogens for PS. FGF1 and FGF7 were
      potent mitogens for PE, but FGF2 was a weak mitogen for these cells. Both PS and
      PE exhibited high affinity binding (pM K) of iodinated-FGF2. The K was 4-fold and
      12-fold higher for PS than for PE cultured from normal prostate and BPH,
      respectively. Northern analysis indicated that PS, but not PE, expressed FGFR
      type 1 (FGFR1) mRNA. The reverse transcriptase polymerase chain reaction (RT-PCR)
      was used to evaluate FGFR type 2 (FGFR2) expression. The size of amplified DNA
      fragments, and nucleotide sequences, indicated that PS also expressed transcripts
      for the exon IIIc RNA splice variant of FGFR2. A RT-PCR product with the FGFR2
      exon IIIb nucleotide sequence joined with the exon IIIc sequence was amplified
      with poly A+ RNA from PE and primers spanning both exons. Thus, PE did not
      alternatively splice mRNA for FGFR2 exon IIIb and exon IIIc. No differences in
      the mitogenic potential of FGFs, receptor binding (K or number of sites), or FGFR
      gene expression were found in cells cultured from normal prostate and BPH.

PMID- 7528518
TI  - Screening for prostate cancer: commentary on the recommendations of the Canadian
      Task Force on the Periodic Health Examination. The U.S. Preventive Services Task
      Force.

PMID- 7528519
TI  - "Screening for prostate cancer".

PMID- 7528521
TI  - [The primary observation of effect on immune function of human body by YAG laser
      tonsillocoagulation].
AB  - Tonsillocoagulation was performed on 50 patients with chronic tonsillitis by
      virtue of YAG Laser. The patients' serum IgG, IgA, IgM, C3level and some acute
      phase reactant proteins (APRPs) including alpha 1-AGP, alpha 1-AT, Tf were
      measured pre- and postoperatively. In addition, tonsillar morphology was observed
      with light and electron microscope before and after tonsillocoagulation.
      Following up the patients for six to twelve months, we discovered that their
      immune function remained normal and that their symptoms of chronic tonsillitis
      had been controlled, it suggests that YAG Laser tonsillocoagulation can be a
      practical therapy for chronic tonsillitis.

PMID- 7528520
TI  - [A case of early-onset and slowly progressive chronic inflammatory demyelinating
      polyneuropathy--electrophysiological findings with clinical course].
AB  - A case of early-onset and slowly progressive chronic inflammatory demyelinating
      polyneuropathy (CIDP) was reported. Her progressive gait disturbance began at six
      years of age and she developed pes cavus. At the age of 13 years, a diagnosis of
      CIDP was made, and oral corticosteroid therapy was started. This therapy was
      effective, but the disease relapsed soon. Muscular strength improved after
      supplementation of an immunosuppressant with oral corticosteroid, following
      steroid pulse therapy. On peripheral motor conduction study, M waves showed very
      low amplitudes and remarkably delayed onset-latencies. New units of M wave
      appeared and amplitudes increased soon after initiation of the corticosteroid
      therapy because of an improvement of conduction block, and durations of M wave
      were prolonged. Then, in accordance with shortening of M wave latencies, some
      dispersed units were synchronized and durations reduced. At relapse, changes of M
      wave showed an inverse relationship to the changes of M wave with clinical
      improvement. The electrophysiological findings started improving 1 week after the
      therapy, while clinical improvement was detected several weeks later. We conclude
      that the change of M wave was a sensitive marker to evaluate the effect of the
      therapy in our CIDP case.

PMID- 7528522
TI  - The dorsal column-medial lemniscal projection of anuran amphibians.
AB  - The efferent connections of the dorsal column nucleus (DCN) of the anuran
      amphibians Rana ridibunda and Xenopus laevis have been studied by means of
      bidirectionally transported tracers. Efferent projections from the DCN innervate
      the spinal cord, tegmentum of the brain stem, cerebellum, torus semicircularis
      and thalamus. The pattern of connectivity of the anuran DCN is largely comparable
      to that of amniotic vertebrates although some peculiarities are found.

PMID- 7528523
TI  - Epitope retrieval--survey and prospect.

PMID- 7528524
TI  - A modified method for antigen retrieval MIB-1 staining of vulvar carcinoma.

PMID- 7528525
TI  - Autoclave heating: an alternative method for microwaving?

PMID- 7528527
TI  - Epitope mapping of human factor IX inhibitor antibodies.
AB  - We have determined the location of epitopes on the factor IX for three
      haemophilia B inhibitor antibodies (HB-1, HB-3, HB-7) and a monoclonal anti
      factor IX inhibitory antibody (designated 65-10). The main binding region of HB
      1, HB-3 and HB-7 was 155YVNSTEAETI164 (residues 155-164), 167NITQSTQSFN176 and
      156VNSTEAETI164, respectively. The binding region of 65-10 was
      168ITQSTQSFNDFTRVV182, which included the cleavage site (180R-V181) for
      activation by factor XIa. By neutralization experiments using two peptides,
      156VNSTEAETI164 and 167NITQSTQSFN176, the degree of neutralization of anti-factor
      IX IgG purified by protein A was determined. Neutralization of three antibodies,
      HB-1, HB-3 and HB-7, in the presence of 10 mM of the peptides 156VNSTEAETI164 was
      30.1%, 0% and 10.8%, respectively, and in the presence of 4 mM of
      167NITQSTQSFN176 it was 0%, 13.5% and 17.3%, respectively. On the other hand,
      when plasmas of patients instead of purified IgG were used for neutralization, 10
      mM of 156VNSTEAETI164 and 4 mM of 167NITQSTQSFN176 failed to neutralize the
      inhibitor in the plasmas.

PMID- 7528528
TI  - Predicting the severity of rhesus alloimmunization: monocyte-mediated
      chemiluminescence versus maternal anti-D antibody estimation.
AB  - Anti-D haemolytic antibody concentration and chemiluminescence (CLT) opsonic
      index was measured in maternal blood obtained from 20 alloimmunized pregnancies
      at 17-28 weeks undergoing intrauterine fetal blood sampling for the estimation of
      fetal haemoglobin concentration. The fetal haemoglobin concentration was
      significantly associated with the maternal serum CLT opsonic index (r = -0.566, P
      < 0.01) but not with the maternal anti-D concentration (r = -0.329). The data of
      this study indicate that measurement of maternal serum CLT opsonic index may be
      more accurate than anti-D quantification in providing non-invasive prediction of
      the degree of fetal anaemia.

PMID- 7528530
TI  - Reducing erythropoietin in cultures of human erythroid precursors elevates the
      proportion of fetal haemoglobin.
AB  - In order to clarify the mechanism of the effect of erythropoietin (Epo) on the
      fetal haemoglobin (HbF) phenotype of peripheral erythrocytes, we studied the dose
      response effect of Epo on HbF production by erythroid precursors derived from the
      peripheral blood of normal adult individuals and grown in a two-phase liquid
      culture system. The proportion of HbF out of the total haemoglobin (Hb) content
      (%HbF) was dependent on the duration of exposure to Epo; on day 6 it comprised up
      to 15%, but dropped to < 2% on day 14. Both cell yield and cellular Hb content
      were markedly increased by high (1 U/ml) Epo, compared to normal physiological
      (20-50 mU/ml) levels, but neither the initial nor final %HbF were dependent on
      the increased Epo dose. However, when cells grown with high Epo were transferred
      on day 7 to low Epo, their progeny contained by day 14 a higher %HbF as compared
      to cells that were continuously exposed to high Epo. This was accompanied by
      acceleration and synchronization of their maturation process, as evidenced by
      their morphology, density and size, and restriction on cell multiplication, as
      indicated by the lower cell yield. These results are consistent with the
      following model. As early erythroid precursors, with relatively high HbF, mature
      under steady-state levels of Epo, HbA production predominates and HbF is diluted.
      However, when such precursors are switched from high to low levels of Epo they
      undergo a synchronized, accelerated maturation which shortens the period of HbA
      production, leading to a decreased Hb content and a relatively high proportion of
      HbF. This mechanism may contribute to the elevated HbF observed following Epo
      administration (due to short half-life of Epo in vivo), and might also explain
      the HbF-augmenting effect of Epo administered together with hydroxyurea observed
      in patients with sickle cell anaemia.

PMID- 7528529
TI  - Cyclic haemopoiesis at 7- or 8-day intervals.
AB  - We report a patient with severe anaemia and cyclic oscillations of reticulocyte
      and leucocyte counts, as well as serum iron (Fe), unsaturated iron-binding
      capacity (UIBC), ferritin, C-reactive protein (CRP) levels and temperature, at
      regular intervals of 7 or 8 d. After treatment with prednisolone, anaemia was
      corrected and the cyclic oscillations of these parameters ceased; whereas
      treatment with indomethacin, recombinant granulocyte-colony stimulating factor (G
      CSF) and erythropoietin (Epo) were unsuccessful.

PMID- 7528526
TI  - Endocrine effects of cytokines.
AB  - Recent trends in antineoplastic therapy include the increasing use of cytokine
      containing regimens. These widely distributed, naturally occurring substances
      play a pivotal role in the physiology of the neuroendocrine/immune system. It is
      not known to what extent the chronic administration of pharmacologic doses of
      exogenous cytokines may create hormonal and metabolic derangements that may, in
      themselves, complicate their therapeutic efficacy. This article reviews the
      endocrine functions of a variety of cytokines. The interferons, for example,
      induce insulin resistance and impaired glucose tolerance, are associated with
      thyroid dysfunction, and can stimulate the ACTH/cortisol axis and growth hormone.
      The hormonal/metabolic actions of the interleukins are being intensively studied,
      especially by bone metabolism, reproductive, and thyroid physiologists. Tumor
      necrosis factor has a profound impact on bone metabolism and remodeling,
      decreases lipoprotein lipase, and can affect thyroid function.

PMID- 7528531
TI  - Serum levels of granulocyte-colony stimulating factor (G-CSF) in bacterial and
      viral infections, and in atypical pneumonia.
AB  - Serum granulocyte-colony stimulating factor (G-CSF) was measured with an ELISA
      method in patients with acute bacterial and viral infections, or with an atypical
      pneumonia. Before initiation of antibiotic treatment, G-CSF was found to be
      significantly increased (799 +/- 1501 ng/l) in sera from 34 patients with an
      acute bacterial infection compared with the 27 patients with a viral infection
      (58 +/- 34 ng/l; P < 0.001) and with the eight patients with an atypical
      pneumonia (60 +/- 33) ng/l; P < 0.001). No significant difference in G-CSF levels
      was seen between gram-positive and gram-negative bacterial infections. In septic
      shock, increased G-CSF levels were seen both in patients with leucocytosis and
      leucopenia. In uncomplicated bacterial infections, both G-CSF and IL-6 were
      increased on day 0, and decreased rapidly after initiation of antibacterial
      therapy and before the patients became afebrile. In bacterial infections on day
      0, G-CSF levels correlated with mononuclear cells (rs = -0.62, P < 0.001), IL-6
      (rs = 0.40, P < 0.05) and S-MPO (rs = -0.5, P < 0.01). In viral infections, G-CSF
      was correlated with mononuclear cells (rs = 0.41, P < 0.05), white blood cell
      counts (rs = 0.56, P < 0.01), neutrophils (rs = 0.41, P < 0.05) and CRP (rs =
      0.47, P < 0.05). We conclude that G-CSF is rapidly raised in the blood in acute
      bacterial infections but not in acute viral infections or in infections with
      Mycoplasma pneumonia. Our results also support the theory that G-CSF is involved
      in the mechanisms of mobilization of neutrophils into the peripheral circulation.

PMID- 7528532
TI  - gamma-mRNA and Hb F levels in beta-thalassaemia.
AB  - The Hb F levels in beta-thalassaemia can be affected by factors both linked and
      unlinked to the beta-globin gene cluster. We have recently analysed a group of
      patients with a homozygosity for the IVS-I-6 (T-->C) mutation, showing a wide
      variation in Hb F levels (2-47%) which could not be accounted for by any sequence
      variation within regulatory elements of the beta-globin gene cluster. In order to
      further investigate factors underlying this phenotypic difference we have
      developed a competitive reverse transcription/polymerase chain reaction procedure
      and used this method to determine the relative amounts of gamma- and beta-mRNAs
      in 10 patients with the IVS-I-6 homozygosity and 15 heterozygous parents, two IVS
      I-6/delta beta-thalassaemia compound heterozygotes, five homozygotes for the
      beta(+) IVS-I-110 (G-->A) mutation, and in two with a homozygosity for the
      beta(0) codon 39 (C-->T) mutation. Three heterozygotes were also included. The
      percentages of gamma/(gamma(+) beta) mRNA were 10-73% in the IVS-I-6 homozygotes
      and < 2% to 10% in their heterozygous parents. A direct relationship existed
      between the level of mRNA and the % Hb F. However, the relative gamma-mRNA levels
      in the IVS-I-6 homozygotes were higher than their Hb F levels, indicating a
      possible competition between the gamma and beta transcripts for translational
      factors with a less efficient initiation of protein synthesis on the gamma-mRNA
      or a preferential survival of cells with mainly beta-globin gene expression at
      the post-reticulocyte stage. The gamma-mRNA levels in the two IVS-I-6/delta beta
      thalassaemia compound heterozygotes were 71% and 62%, similar to their Hb F
      levels (63% and 59%), and averaged 82% (range 65-91%) in the five IVS-I-110
      homozygotes, and 97.5% in the two codon 39 homozygotes. The correlation between
      these values and the % Hb F could not be evaluated because of the transfusion
      regimens; however, the levels of gamma-mRNA were as expected for patients with
      these beta-thalassaemia alleles.

PMID- 7528533
TI  - Management of pregnancy when maternal blood has a very high level of fetal
      haemoglobin.
AB  - Fetal blood normally has a higher oxygen affinity than maternal blood because of
      the predominance of haemoglobin (Hb) F in the former and of Hb A in the latter;
      this predominance facilitates the transfer of oxygen from maternal to fetal
      blood. We report two patients who had exclusively or predominantly Hb F in their
      blood and were managed differently. When patient 1 became pregnant she had
      regular exchange blood transfusions in order to reduce her Hb F from 80% to below
      50%; patient 2, who had 100% Hb F, was not transfused before, during or after her
      pregnancy. Each patient delivered a normal healthy baby. We conclude that the
      differential oxygen affinity produced by the combination of Hb A in the maternal
      blood and Hb F in the fetal blood is not indispensable to ensure an oxygen supply
      adequate for normal fetal development and growth.

PMID- 7528534
TI  - Interferon alfa-2a modifies the course of subfoveal and juxtafoveal choroidal
      neovascularisation.
AB  - The first double masked placebo controlled trial of interferon alfa-2a for the
      treatment of overt choroidal neovascular membranes is presented. A total of 43
      consecutive patients were randomised to double masked treatment with either
      interferon alfa-2a, 3 million IU subcutaneously three times a week or matching
      placebo, for a period of 8 weeks. End of study changes from baseline in distance
      and near visual acuity, macular visual field, contrast sensitivity, and macular
      morphology (fluorescein angiography) were assessed. The between group difference
      in distance visual acuity, the primary efficacy variable, was significant in
      favour of interferon alfa-2a (p = 0.023). Fluorescein angiograms, macular visual
      fields, and near vision all showed a trend in favour of interferon alfa-2a. It
      was concluded that, at the dosage used in this study, interferon alfa-2a is a
      reasonably well tolerated and apparently effective short term treatment of
      subfoveal and juxtafoveal choroidal neovascularisations.

PMID- 7528537
TI  - Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function
      for Src homology 2 domains.
AB  - The steady-state kinetic properties of SH-PTP1 (PTP1C, SHP, HCP), a Src homology
      2 (SH2) domain-containing protein tyrosine phosphatase (PTPase), were assessed
      and compared with those of three truncation mutants, using p-nitrophenyl
      phosphate, phosphotyrosyl (pY) peptides, and reduced, carboxyamido-methylated,
      maleylated, and tyrosyl-phosphorylated lysozyme as substrates. At physiological
      pH (7.4), truncation of the two N-terminal SH2 domains [SH-PTP1(delta SH2)] or
      the last 35 amino acids of the C-terminus [SH-PTP1(delta C35)] activated the
      phosphatase activity by 30-fold and 20-34-fold relative to the wild-type enzyme,
      respectively. Truncation of the last 60 amino acids resulted in a mutant [SH
      PTP1(delta C60)] with wild-type activity. SH-PTP1 and SH-PTP1(delta C60)
      displayed apparent saturation kinetics toward pNPP only at acidic pH (pH < or =
      5.4); as pH increased above 5.5, their apparent KM values increased dramatically.
      In contrast, SH-PTP1(delta SH2) obeyed normal Michaelis-Menten kinetics at all pH
      values tested (pH 5.1-7.4) with a constant KM (10-14 mM). Furthermore, two
      synthetic pY peptides corresponding to known and potential phosphorylation sites
      on the erythropoietin (EPOR pY429) and interleukin-3 (IL-3R pY628) receptors
      bound specifically to the N-terminal SH2 domain of SH-PTP1 (KD = 1.8-10 microM)
      and activated the catalytic activity of SH-PTP1 and SH-PTP1(delta C60) but not SH
      PTP1(delta SH2), in a concentration-dependent manner. Maximal activation (25-30
      fold) of SH-PTP1 was achieved at 70 microM EPOR pY429, and the maximally
      activated enzyme approached the activity of SH-PTP1(delta SH2). Addition of EPOR
      pY429 peptide, which corresponds to the recently identified in vivo binding site
      for SH-PTP1, at 40 microM also completely restored the saturation kinetic
      behavior of SH-PTP1 (at pH 7.4) toward pNPP, with catalytic parameters (KM = 12.8
      mM, kcat = 3.2 s-1) similar to those of SH-PTP1(delta SH2). These data suggest
      that the SH2 domains of SH-PTP1 serve to autoinhibit the phosphatase activity of
      the PTPase domain. A model is proposed in which the SH2 domains interact with the
      PTPase domain in a pY-independent fashion and drive the PTPase domain into an
      inactive conformation.

PMID- 7528536
TI  - Semisynthetic proteins: model systems for the study of the insertion of
      hydrophobic peptides into preformed lipid bilayers.
AB  - Models of protein translocation and secretion will not be complete without
      details of the mechanism of lipid bilayer insertion. The study of spontaneous
      hydrophobic peptide interactions with model membrane systems has been hindered by
      their very low solubility in aqueous solutions. A novel protocol has been
      developed that enables the site-specific (N-terminus) attachment of hydrophobic
      peptides to a water-soluble carrier protein [bovine pancreatic trypsin inhibitor
      (BPTI)] using a heterobifunctional crosslinker (SPDP). In this initial study H
      (Ala)20-Tyr-Cys-CONH2 and H-(Ala)10-Tyr-Cys-CONH2 were selected as hydrophobic
      peptides, since alanine is the simplest alpha-helix-forming amino acid, and the
      peptides as alpha-helices are just long enough to span the lipid bilayer and
      monolayer, respectively. The carrier protein was treated with sigma
      methylisourea, which resulted in the guanidination of the four lysine epsilon
      amine groups. The chemical modification of BPTI to give G-BPTI allowed the
      attachment of SPDP specifically to the free N-terminal alpha-amine group. The
      peptides were synthesized with a C-terminal cysteine moiety, allowing the site
      specific cross-linking of the peptides to the N-terminus. In order to prevent
      peptide aggregation, the synthetic peptides were cleaved from the preparative
      resin in detergent and cross-linked to G-BPTI. After cross-linking, the detergent
      was removed from the mixture by gel filtration employing propionic and formic
      acids in the mobile phase. The detergent-free, peptide--G-BPTI conjugates were
      subsequently purified by reversed-phase HPLC. The interaction parameters of the
      two semisynthetic proteins with large unilamellar vesicles were determined by
      ultracentrifugation of the equilibrated vesicle--protein mixtures. For
      comparison, the same semisynthetic proteins were reconstituted into lipid
      vesicles using an octyl glucoside dilution technique. The incorporation and
      reconstitution data proved to be quite similar. The results indicated that
      (Ala)20--G-BPTI interacted with LUV to form a stable complex and behaved as a
      membrane protein in reconstituted bilayer systems. (Ala)10--G-BPTI, however,
      remained in the aqueous phase in both bilayer systems. The thermodynamic
      interaction data are compared to the theoretical values of total free energy
      changes calculated for the incorporation of model hydrophobic alpha-helices. In
      addition, the solubility and stability of the hydrophobic peptides, both in the
      aqueous phase and membrane-bound, were studied by cleaving the disulfide bond
      linking the peptides to G-BPTI using dithiothreitol. Molecular sieve
      chromatography was used to evaluate the state of self-association of the
      semisynthetic proteins in aqueous solutions.

PMID- 7528538
TI  - Aprotinin therapy for insertion of ventricular assist devices for staged heart
      transplantation.
AB  - Bleeding after insertion of ventricular assist devices is a common problem which
      carries a major risk of immediate and late complications. We evaluated the safety
      and efficacy of aprotinin in six patients undergoing staged heart transplantation
      and compared the results with those of six patients who received no aprotinin.
      The groups did not differ significantly with respect to age, gender, preoperative
      cause of cardiomyopathy, or cardiopulmonary bypass time. Patients treated with
      aprotinin had a significant reduction in postoperative chest tube drainage (743
      +/- 457 versus 2036 +/- 1184 cc, respectively, for aprotinin therapy versus no
      therapy; p = 0.047). Blood transfusion requirements were reduced in patients
      treated with aprotinin (2.2 +/- 2.2 versus 10.7 +/- 7.1 U respectively, for
      aprotinin therapy versus no therapy; p = 0.038). No demonstrable serious side
      effects were attributed to the aprotinin treatment. We conclude that aprotinin is
      effective in reducing bleeding and transfusion requirements without increasing
      the incidence of clinically significant renal dysfunction or thromboembolic
      events.

PMID- 7528535
TI  - Huntington's disease: pathogenesis, diagnosis and treatment.
AB  - This review of the clinical features of Huntington's disease incorporates recent
      developments in pathophysiology, preclinical diagnosis and treatment. Although
      the mechanism initiating and guiding the cell destruction in this illness is
      currently unknown, the excitatory neurotoxin and the energy metabolism models may
      provide a valuable direction for future research. Similarly, although the precise
      relation between the neuroanatomical damage in Huntington's disease and the
      functional disability is not clear, applications of recently developed neural
      connection models have implicated a number of important brain-behavior
      associations. Preclinical diagnostic procedures have evolved through successive
      iterations that have each contributed to increased reliability. New functional
      brain imaging techniques are sure to add to this promising domain in the future.
      Preclinical diagnosis has been stimulated by the recent isolation of the
      Huntington's gene which has also rekindled awareness of the importance of
      informed genetic counselling and the inherent ethical dilemmas in genetic
      testing. Treatment approaches to Huntington's disease have been confined to
      palliative care with secondary symptom management and psychotherapeutic support.
      Experimental therapeutic strategies for the illness itself have had a rather
      disappointing record to date. Further developments in NMDA antagonism and neural
      cell grafting may provide some hope for the future.

PMID- 7528543
TI  - Supportive care.

PMID- 7528541
TI  - Factors influencing macrophage activation by muramyl peptides: inhibition of NO
      synthase activity by high levels of NO.
AB  - Treatment with muramyldipeptide (MDP) or a lipophilic derivative (MTP-Chol)
      included in nanocapsules renders macrophages cytostatic towards tumor cells. At
      the same time, nitric oxide (NO) synthase (EC 1.14.23) activity is induced, as
      determined by measurement of the two end products of the reaction (nitrite and L
      citrulline). The objective of this study was to investigate some factors which
      might influence this activation and explain the decreased response observed at
      high nanocapsule concentrations. The glucose content of the medium did not seem
      to be limiting. Addition of indomethacin decreased nitrite production in the
      effector phase, suggesting a role for prostaglandins in the maintenance of the
      activated state. We also tested the hypothesis that NO itself might regulate
      inducible nitric oxide synthase activity. The addition of NO donors (SIN-1 and
      nitrosoglutathione) or superoxide dismutase to cultures of activated macrophages
      inhibited the NO synthase activity. Since these NO donors were non toxic towards
      macrophages, these observations indicate clearly that the addition of exogenous
      NO to that formed by the enzymatic reaction can cause inhibition of the inducible
      NO synthase.

PMID- 7528542
TI  - A long-term follow-up study of cerebrospinal fluid 5-hydroxyindoleacetic acid in
      delirium.
AB  - Cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) was determined for
      elderly delirious patients during the acute stage and after a 1-year follow-up
      period, and the 5-HIAA levels were compared with age-equivalent controls. As
      compared with the controls, the 5-HIAA levels were significantly higher at the
      beginning of the index admission in patients with multi-infarct dementia and
      patients with no apparent CNS disease. The 5-HIAA levels were also higher in the
      latter subgroup in the 1-year sampling, but no other differences between
      delirious patients and controls were observed. The one-way procedure showed no
      differences between the subgroup means of delirious patients when divided
      according to the severity of cognitive decline or type of delirium in any of the
      samples. The 5-HIAA levels measured during the index admission correlated with
      the length of life after delirium suggesting that serotonergic dysfunction may
      have prognostic significance in delirious patients.

PMID- 7528539
TI  - Twenty-four-hour ice storage of rabbit heart.
AB  - Although cardioplegia is limited to 4 hours of ice storage, University of
      Wisconsin solution has successfully extended this period to approximately 12
      hours. In this study we have substituted polyethylene glycol for hydroxyethyl
      starch in a simplified University of Wisconsin solution (Cardiosol). Rabbit
      hearts were ice stored for 24 hours at 0 degrees C in either University of
      Wisconsin solution or Cardiosol (containing either 5% or 10% polyethylene
      glycol). Fresh control hearts were tested immediately after cardiectomy. Function
      was evaluated in an in vitro working heart model for 1 hour with aortic afterload
      at 100 cm H2O. Total cardiac output or the proportion of hearts reaching 100 cm
      H2O were compared. Hearts stored in University of Wisconsin solution for 24 hours
      functioned at 6% of control levels at 15 minutes of observation. None reached 100
      cm H2O or deteriorated further with time (p < 0.05). By contrast, hearts stored
      in 5% Cardiosol showed progressive recovery during the 1-hour observation. Of the
      13 hearts, 11 reached 100 cm H2O with a mean cardiac output of 51% of the control
      value. Increasing the concentration of polyethylene glycol to 10% improved
      cardiac output at all observation times, reaching 80% of control heart
      performance at 1 hour (control > 10% > 5% > University of Wisconsin solution [p <
      0.05]). We concluded that 10% polyethylene glycol significantly improved 24-hour
      ice storage and, hence, viability to a functional level that matched our
      previously reported microperfusion results.

PMID- 7528544
TI  - Supportive care.
AB  - For cancer patients, quality of life and satisfaction with care are not only
      related to patient treatment facilities, but also to ambulatory care. Therefore,
      the goal of ambulatory care should be to prevent predictable morbidities, to
      eliminate residual morbidities when possible, to control symptoms, and to lessen
      discomfort when cure is not likely. Truly multidisciplinary services should be
      available and assessed for their effectiveness, the aim being to respond
      optimally to patients' needs, whether or not these needs are related to the
      disease or treatment. Research in this area is urgently needed.

PMID- 7528540
TI  - Isolation and characterization of circulating complex between human pregnancy
      associated plasma protein-A and proform of eosinophil major basic protein.
AB  - The plasma protein previously known as pregnancy associated plasma protein-A
      (PAPP-A) and believed to contain only one kind of polypeptide chain has recently
      been shown to be a complex containing two different chains in equimolar amounts.
      One of the chains is now defined as the PAPP-A subunit, and the other has been
      identified as the proform of eosinophil major basic protein (proMBP) (Oxvig et
      al. (1993) J. Biol. Chem. 268, 12243-12246). A procedure for large scale
      preparation of the circulating complex (PAPP-A/proMBP) from pooled pregnancy
      serum is described. The amino acid and carbohydrate compositions of the isolated
      reduced and carboxymethylated PAPP-A (199 kDa) and proMBP subunits (38 kDa), and
      of the intact PAPP-A/proMBP have been determined. The PAPP-A and proMBP subunits
      contain 13.4% (w/w) and 38.6% (w/w) carbohydrate, respectively, and the intact
      complex contains 17.4% (w/w) carbohydrate. The PAPP-A subunit contains N-bound
      carbohydrate groups. In contrast, the proMBP subunit contains both N- and O-bound
      groups as well as glycosaminoglycan, previously found among plasma proteins only
      in inter-alpha-trypsin inhibitor and pre-alpha-trypsin inhibitor. It is shown
      that PAPP-A/proMBP can competitively inhibit human leucocyte elastase (KI = (5
      10) x 10(-9) M) at an ionic strength of 0.075, but the inhibition is negligible
      at ionic strengths greater than 0.15. Human cathepsin G is also competitively
      inhibited (KI approx. 1 x 10(-6) M). The inhibition of both enzymes is most
      likely due to interactions with the glycosaminoglycan moiety of PAPP-A/proMBP. It
      is concluded that PAPP-A/proMBP is neither a potent nor a specific inhibitor of
      human leucocyte elastase.

PMID- 7528545
TI  - Ambulatory supportive care for the cancer patient.
AB  - The recent literature on ambulatory supportive care for the cancer patient
      encompasses a wide area. Those topics that have been most dominant are reviewed
      in this article, including the roles of primary care physicians and specialists,
      symptom control in the palliative-care patient, quality-of-life issues, and
      economic considerations.

PMID- 7528546
TI  - Management of bowel obstruction in advanced cancer.
AB  - Bowel obstruction is a common and distressing outcome in patients with abdominal
      or pelvic cancer. Patients may develop bowel obstruction at any time in their
      clinical history, with a prevalence ranging from 5.5% to 42% in those with
      ovarian cancer and from 10% to 28.4% in those with colorectal cancer. The causes
      of the obstruction may be benign postoperative adhesions, a focal malignant or
      benign deposit, or relapse or diffuse carcinomatosis. The symptoms, which are
      almost always present, are intestinal colic, continuous abdominal pain, nausea,
      and vomiting. Although surgery should be the primary treatment for malignant
      obstruction, it is now recognized that some patients with advanced disease or in
      generally poor condition are unfit for surgery and require alternative management
      to relieve distressing symptoms. A number of treatment options are now available
      for the patient with advanced cancer who develops intestinal obstruction. In this
      review, the indications for surgery are examined, the use of nasogastric tube and
      percutaneous gastrostomy evaluated, and the pharmacologic approach described.

PMID- 7528547
TI  - Endoscopic techniques in gastrointestinal oncology.
AB  - Gastrointestinal endoscopy continues to play a significant role in
      gastroenterologic oncology. As a diagnostic tool, it has largely replaced
      radiology in diseases of the gastrointestinal tract because of its capability to
      provide a tissue diagnosis by endoscopic biopsy. The still-expanding therapeutic
      potential of gastrointestinal endoscopy represents the prototype of minimal
      invasive therapy. This review deals with relevant papers on diagnostic and
      therapeutic gastrointestinal endoscopy during the past 2 years. The abundance of
      studies renders a detailed discussion of all or even most of them impossible;
      therefore, only trends are shown. The reader is referred to the annotations in
      the reference list for more detailed information.

PMID- 7528548
TI  - Detection of insulin-like growth factor binding protein-1 in cat implantation
      sites.
AB  - This study was undertaken to determine whether insulin-like growth factor binding
      protein-1 (IGFBP-1) was synthesized by the cat uterus and placenta during
      implantation and pregnancy. Endometrial and placental tissue explants from
      pregnant, pseudopregnant, and ovariectomized steroid-treated cats were cultured
      in the presence of 35S-methionine. Culture media proteins were separated by one
      dimensional (1-D) and two-dimensional (2-D) SDS-PAGE, transferred to
      nitrocellulose, and immunostained using a rabbit polyclonal antibody against
      baboon IGFBP-1 and a murine monoclonal antibody to human IGFBP-1. The antibody
      cross-reacted with a protein with an M(r) = 30,000 and a pI = 5.1-5.4.
      Immunoreactive product was found in implantation site media from 16 days
      postcoitum (PC) through the end of pregnancy, and was confined to the superficial
      placental/junctional zone. Immunoreactivity was not detected in non-implantation
      site media until 7 wk PC and was never detected in serum or in media from liver,
      pseudopregnant endometrium, or endometrium from steroid-treated cats.
      Autoradiography and immunostaining of 2-D Western blots of culture media proteins
      demonstrated that implantation site and not non-implantation site tissue
      synthesized and released immunoreactive IGFBP-1 into the culture medium.
      125Insulin-like growth factor-1 (IGF-1) specifically bound to this protein on 1-D
      Western ligand blots. Avidin-biotin immunocytochemistry utilizing the monoclonal
      antibody was used to localize IGFBP-1 in paraffin sections. Specific
      immunostaining was observed in the surface and glandular epithelium of the non
      site endometrium throughout pregnancy, with stromal cell staining being detected
      later.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528549
TI  - Localization of endoglin, a transforming growth factor-beta binding protein, and
      of CD44 and integrins in placenta during the first trimester of pregnancy.
AB  - Endoglin is an integral membrane glycoprotein that binds transforming growth
      factor-beta 1 (TGF beta 1) with high affinity and is predominantly expressed on
      human endothelial cells. Characterization of this homodimeric protein from human
      term placenta has shown that it is particularly abundant on the
      syncytiotrophoblast. Immunofluorescence staining of sections of first trimester
      placenta now reveals that endoglin is found at even higher levels on the
      syncytiotrophoblast of samples ranging from 6 to 12 wk of gestation. Very low
      levels are observed on the undifferentiated cytotrophoblast cells that can be
      identified by their expression of the alpha 6 beta 4 integrin, a receptor for
      laminin. Within the villi, blood vessels and stromal cells are negative for
      endoglin but positive for alpha 1 beta 1 integrin, a receptor for collagens and
      laminin. Stromal cells also express CD44, a hyaluronic acid receptor. Of
      particular interest is the up-regulation of endoglin expression in the transition
      from polarized undifferentiated to non-polarized intermediate cytotrophoblasts
      (CTB) as the cells align in columns to invade the uterus. This occurs in parallel
      with the acquisition of alpha 5 beta 1 integrin (fibronectin receptor) and
      precedes the loss of alpha 6 beta 4 integrin. CD44 and alpha 1 beta 1 integrin
      are noticeably absent from the CTB within the columns but are expressed at very
      high levels throughout the placental bed. Endoglin is undetectable within the
      decidua; thus, intermediate CTB that have invaded the placental bed express alpha
      5 beta 1 integrin and cytokeratins but not endoglin.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7528550
TI  - Developmental potential of rhesus monkey embryos produced by in vitro
      fertilization.
AB  - This study was an examination of the developmental potential of in vitro
      fertilization (IVF)-produced rhesus monkey embryos that were cultured in medium
      alone or cocultured with various cell types. End points were the quality and
      yield of embryos attaining the expanded or hatched blastocyst stage. A total of
      96 IVF-produced embryos were cryopreserved and thawed, and 90 embryos were
      considered intact and suitable for culture. These embryos were placed into one of
      five treatment groups consisting of four different cell supports and medium
      alone. Two primary cultures (bovine oviductal cells [bOVID] and bovine cumulus
      cells [bCUM]) and two established cell lines (Vero cells and buffalo rat liver
      cells [BRL]) were utilized for coculture of embryos. Embryos were cultured for up
      to 14 days, and growth curves were established for all embryos that expanded
      and/or hatched. The developmental rate for embryos classified as viable varied
      substantially; in number of days to reach a given stage, early morulae ranged
      from Days 3 to 9 post-insemination, morulae from Days 4 to 9, blastocysts from
      Days 6 to 11, expanded blastocysts from Days 7 to 12, and hatched blastocysts
      from Days 9 to 15. On the basis of developmental curves, 30% of the embryos were
      arrested upon thawing or shortly after. Of the remaining embryos classified as
      viable, developmental efficiencies to the hatched blastocyst stage for the
      various treatments were 1) bOVID, 33%; 2) bCUM, 15%; 3) Vero cells, 9%; 4) BRL,
      45%; and 5) medium alone, 8%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528551
TI  - Leukocyte populations of the adult rat testis following removal of the Leydig
      cells by treatment with ethane dimethane sulfonate and subcutaneous testosterone
      implants.
AB  - The influence of the Leydig cells on the leukocyte population of the testis was
      investigated. Leydig cells were destroyed by ethane dimethane sulfonate (EDS)
      treatment in adult male rats, with or without low-dose s.c. testosterone implants
      to prevent Leydig cell recovery. Leukocytes were counted in perfusion-fixed
      frozen testis sections, by use of cell-specific monoclonal antibodies (mAbs) with
      immunoperoxidase detection, or toluidine blue staining. The majority (81%) of
      testicular leukocytes (OX1+) were immunopositive for the resident macrophage
      specific mAb, ED2, and/or the monocyte/macrophage/dendritic cell mAb, ED1. The
      remaining leukocytes were principally T lymphocytes (R73+). B lymphocytes (OX33+)
      and metachromatic mast cells were not observed in the normal testis. Treatment
      with EDS caused a transient increase in ED1+, ED2+, and R73+ cell numbers in the
      testis, although other evidence of an inflammatory reaction, such as increases in
      major histocompatibility complex class II antigen, interleukin-2 receptor
      expression, or capillary permeability, were not observed. At 21 days after EDS
      treatment, there was a significant decline in macrophage numbers (to
      approximately 50% of control testis), and T lymphocytes returned to pretreatment
      levels. After Leydig cell recovery (41 days after treatment), macrophages also
      returned to pretreatment levels in EDS-treated rats, but remained reduced in EDS
      treated animals with testosterone implants. In addition, EDS treatment stimulated
      a progressive increase in intertubular mast cells, which was significantly
      inhibited in the testosterone-implanted rats. The data indicate that numbers of
      testicular macrophages and mast cells, but not of lymphocytes, within the adult
      rat testis are directly or indirectly regulated by the Leydig cells.

PMID- 7528553
TI  - Persistent infection with Bartonella (Rochalimaea) henselae or Afipia felis is
      unlikely to be a cause of chronic fatigue syndrome.

PMID- 7528552
TI  - Haemophilus parainfluenzae endocarditis: application of a molecular approach for
      identification of pathogenic bacterial species.
AB  - Haemophilus parainfluenzae is both a human oropharyngeal commensal bacterium and
      a cause of serious invasive disease. The fastidious growth characteristics of
      this organism and the poor specificity of traditional methods for species
      identification are likely to have led to inaccuracies in the diagnosis of
      infections caused by H. parainfluenzae and related organisms. We report a case of
      H. parainfluenzae endocarditis in which confusion related to microbial
      identification was resolved by the analysis of 16S ribosomal RNA sequences. Rapid
      identification was facilitated by amplification of 16S ribosomal DNA directly
      from cultured cells with use of the polymerase chain reaction and by direct DNA
      sequence determination of the amplified product. This procedure is potentially
      useful for the identification of fastidious bacterial pathogens by reference
      laboratories.

PMID- 7528556
TI  - Methods of early detection of prostate cancer: the role of prostatic specific
      antigen, transrectal ultrasound and digital rectal examination.
AB  - PSA has significantly influenced the management of prostate cancer. Early
      detection of clinically significant cancer has been increased by combining PSA
      and digital rectal examination. PSA has been used as a prognostic factor for
      patients with local disease and as a monitoring test for patients undergoing
      curative therapy for localized prostate cancer.

PMID- 7528557
TI  - Benign prostatic hyperplasia: it is a premalignant lesion?
AB  - Benign prostatic hyperplasia (BPH) and prostate cancer are conditions commonly
      affecting the prostate gland in aging men. Prior epidemiological studies
      investigating potential associations between the two have resulted in conflicting
      data. Recent morphological studies have demonstrated the occurrence of a subset
      of prostate cancers as arising in the transition zone of the gland, the same
      region where BPH occurs. A morphologic lesion, atypical adenomatous hyperplasia
      (AAH), providing a possible link between cancer and BPH has been described.
      Biological studies of this potential precursor lesion are not yet available, but
      will be essential in order to further investigate this possible association.

PMID- 7528554
TI  - [Are our transparencies illustrative?].

PMID- 7528555
TI  - Controversies in the early detection of prostate cancer.
AB  - Fundamental issues about early detection of prostate cancer are unresolved. There
      is controversy over the need for early detection of prostate cancer, based on a
      relatively small number of lifeyears lost to prostate cancer when compared with
      other types of cancers. Earlier detection of prostate cancer is possible with PSA
      driven strategies based on evidence that there is an interval of probably several
      years when the PSA is abnormal but the prostate cancer is still in the curative
      state. Earlier detection may only be advisable in men with risk for premature
      death from prostate cancer, i.e., younger men. Immediate problems in early
      detection of prostate cancer include, 1) An apparent indiscriminate use of PSA in
      all age groups; 2) Probable over treatment in some older patients; and 3)
      Morbidity from currently available therapies. Physician education about the use
      of PSA can be accomplished now. More precise characterization of the morbidity of
      treatment is needed; efforts to improve the quality of surgery, radiation
      therapy, or alternative treatments are warranted. A marvelous opportunity and
      challenge are presented in a disease that will become an increasingly important
      health care issue in our society.

PMID- 7528558
TI  - Prostate cancer trends in southeast Michigan 1973-1992.
AB  - Prostate cancer incidence has been increasing in the United States (US) for many
      decades. This increased has been accelerating since 1989. It is speculated that
      this trend of increased incidence is due primarily to the use of the prostate
      specific antigen (PSA) screening test. This study describes prostate cancer
      trends in southeast Michigan since 1973.

PMID- 7528560
TI  - Does aprotinin influence endothelial-associated coagulation in cardiac surgery?
AB  - Aprotinin has been reported to reduce bleeding in cardiac surgery patients. Its
      mechanisms of action on coagulation have not been fully elucidated. In a
      prospectively randomized study of 40 patients undergoing elective aortocoronary
      bypass grafting, the influence of high-dose aprotinin (2 million IU of aprotinin
      before CPB, 500,000 IU/h until the end of operation, 2 million IU added to the
      prime) (N = 20) on endothelial-related coagulation was compared to a nontreated
      control group (N = 20). Thrombomodulin (TM), protein C and (free) protein S as
      well as thrombin/antithrombin-III (TAT) plasma concentrations were measured by
      enzyme-linked immunosorbent assays (ELISA) before the aprotinin infusion, before
      cardiopulmonary bypass (CPB), during CPB and after CPB, at the end of surgery, 5
      hours after CPB, and on the first postoperative day. All standard coagulation
      parameters (AT-III and fibrinogen plasma levels, platelet count, partial
      thromboplastin time) did not differ between the two groups. At baseline, TM
      plasma levels were within the normal range (< 40 ng/mL) and similar in both
      groups. During CPB, TM plasma concentrations decreased similarly in both groups
      (aprotinin: 18 +/- 6 ng/mL, control: 17 +/- 7 ng/mL) followed by a comparable
      increase in the postbypass period until the first postoperative day (aprotinin:
      60 +/- 10 ng/mL, control: 53 +/- 11 ng/mL). Protein C and (free) protein S plasma
      levels also showed no differences between the two groups. On the first
      postoperative day, baseline values for protein C and protein S had not yet been
      reached.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528561
TI  - Protein tyrosine kinases, with emphasis on the Src family.
AB  - Protein tyrosine phosphorylation is recognized to be an important regulatory
      event, particularly in those pathways that control cell growth and
      differentiation. Phosphorylation on tyrosine may either decrease or increase the
      enzymatic activity of substrate proteins. In addition, tyrosine phosphorylated
      sequences associate with Src homology 2 (SH2) domains, and thus tyrosine
      phosphorylation also serves to regulate protein/protein interactions. Many
      protein tyrosine kinases have been described to date: several are the receptors
      for peptide growth factors; others are expressed in the cytoplasm and nucleus.
      The main subject of this review will be the Src family of protein tyrosine
      kinases, a group of nine enzymes thought to play important roles in several
      signal transduction pathways.

PMID- 7528559
TI  - Xenografts of human benign prostatic hyperplasia tissues in the nude mouse.
AB  - Human benign hyperplastic prostate (BHP) tissues were implanted subcutaneously in
      male Beige nude mice for up to 16 weeks. The implants maintained the normal
      histological appearance of BPH without signs of atrophy for up to 6 weeks.
      Thereafter the tissues gradually became atrophic, with the tendency to undergo
      squamous cell metaplasia, but some tissues still maintained normal epithelium at
      16 weeks. The epithelial linings of the implants consistently expressed prostate
      specific antigen and prostate acid phosphatase, as demonstrated by
      immunohistochemistry, except in areas of severe atrophy and squamous metaplasia.
      Continued feeding of the mice with dihydrotestosterone or hydrocortisone did not
      change significantly the morphology or the proliferation index of the epithelial
      cells within implants or host prostates.

PMID- 7528562
TI  - Rapid engraftment by peripheral blood progenitor cells mobilized by recombinant
      human stem cell factor and recombinant human granulocyte colony-stimulating
      factor in nonhuman primates.
AB  - We have previously shown that administration of low-dose recombinant human stem
      cell factor (rhSCF) plus recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood
      than does administration of rhG-CSF alone. The purpose of the present study was
      to determine whether marrow repopulating cells are present in the blood of
      nonhuman primates administered low-dose rhSCF plus rhG-CSF, and if present,
      whether these cells engraft lethally irradiated recipients as rapidly as blood
      cells mobilized by treatment with rhG-CSF alone. One group of baboons was
      administered low-dose rhSCF (25 micrograms/kg/d) plus rhG-CSF (100
      micrograms/kg/d) while a second group received rhG-CSF alone (100
      micrograms/kg/d). Each animal underwent a single 2-hour leukapheresis occurring
      the day when the number of progenitor cells per volume of blood was maximal. For
      baboons administered low-dose rhSCF plus rhG-CSF, the leukapheresis products
      contained 1.8-fold more mononuclear cells and 14.0-fold more progenitor cells
      compared to the leukapheresis products from animals treated with rhG-CSF alone.
      All animals successfully engrafted after transplantation of cryopreserved
      autologous blood cells. In animals transplanted with low-dose rhSCF plus rhG-CSF
      mobilized blood cells, we observed a time to a platelet count of > 20,000 was 8
      days +/- 0, to a white blood cell count (WBC) of > 1,000 was 11 +/- 1 days, and
      to an absolute neutrophil count (ANC) of > 500 was 12 +/- 1 days. These results
      compared with 42 +/- 12, 16 +/- 1, and 24 +/- 4 days to achieve platelets >
      20,000, WBC > 1,000, and ANC > 500, respectively, for baboons transplanted with
      rhG-CSF mobilized blood cells. Animals transplanted with low-dose rhSCF plus rhG
      CSF mobilized blood cells had blood counts equivalent to pretransplant values
      within 3 weeks after transplant. The results suggest that the combination of low
      dose rhSCF plus rhG-CSF mobilizes greater numbers of progenitor cells that can be
      collected by leukapheresis than does rhG-CSF alone, that blood cells mobilized by
      low-dose rhSCF plus rhG-CSF contain marrow repopulating cells, and finally that
      using a single 2-hour leukapheresis to collect cells, the blood cells mobilized
      by low-dose rhSCF plus rhG-CSF engraft lethally irradiated recipients more
      rapidly than do blood cells mobilized by rhG-CSF alone.

PMID- 7528564
TI  - Stem cell factor modulates avidity of alpha 4 beta 1 and alpha 5 beta 1 integrins
      expressed on hematopoietic cell lines.
AB  - Interactions between hematopoietic cells and bone marrow (BM) stroma, composed of
      extracellular matrix and stromal cells, are crucial for hematopoiesis. Integrins
      facilitate these interactions by mediating adherence of hematopoiesis. Integrins
      facilitate these interactions by mediating adherence of hematopoietic cells to
      both the extracellular matrix and stromal cells. Marrow stromal cells secrete a
      variety of growth factors, including stem cell factor (SCF). Because treatment
      with SCF in vivo mobilizes primitive hematopoietic cells from the BM, we
      investigated the effect of the growth factor SCF of hematopoietic cell adhesion.
      These studies show that SCF modulates adhesive function in a dose- and time
      dependent manner, but does not modulate expression of the integrins alpha 4 beta
      1 and alpha 5 beta 1 in the SCF-responsive cell line MO7E. Treatment of MO7E
      cells with SCF (200 ng/mL) produced a transient increase in adherence to cytokine
      activated human umbilical vein endothelial cells (HUVECs) or to vascular cell
      adhesion molecule 1 (VCAM-1)-transfected Chinese hamster ovary (CHO) cells with
      peak adhesion at 30 minutes and return to baseline by 60 to 90 minutes. This
      increase in adhesion was paralleled by increased binding of the beta 1 activation
      dependent monoclonal antibody (MoAb) 15/7, as determined by flow cytometry.
      However, prolonged incubation of MO7E with SCF induced a marked decrease in
      integrin-mediated adherence, with maximal inhibition by 24 hours. No change in
      expression of integrins, as determined by flow cytometry, was observed with short
      or long-term incubation with SCF. SCF-treated cells were still able to respond
      to phorbol esters and to the activating beta 1 MoAb 8A2 with increased adherence,
      but not to the level seen in control cells. This suggests that a subpopulation of
      expressed alpha 4 beta 1 and alpha 5 beta 1 integrins is disengaged by prolonged
      incubation with SCF.

PMID- 7528566
TI  - Increased expression of the multidrug resistance-associated protein gene in
      relapsed acute leukemia.
AB  - Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to
      determine relative levels of transcripts for MDR1 and the recently described
      multidrug resistance-associated protein (MRP) in normal lymphohematopoietic cells
      and in 62 bone marrow aspirates of newly diagnosed and recurrent acute leukemia.
      Levels of MRP expression in newly diagnosed AML samples were similar to those
      observed in normal bone marrow cells (CD34-negative and CD34-positive) and in
      unselected HL60 human promyelocytic leukemia cells, which were used as an
      internal control throughout this study. In contrast, samples of AML obtained at
      the time of relapse contained approximately twofold higher levels of MRP RNA (P <
      .01). Analysis of paired samples, the first obtained at diagnosis and the second
      at relapse, from 13 acute myelogenous leukemia (AML) and four acute lymphocytic
      leukemia (ALL) patients showed that MRP expression was increased at the time of
      relapse in greater than 80% of patients. In contrast, no consistent changes of
      MDR1 expression at relapse were observed. These results raise the possibility
      that increased MRP expression might contribute to leukemic relapse.

PMID- 7528565
TI  - Heterotypic adherence between human B-lymphoblastic and pre-B-lymphoblastic cells
      and marrow stromal cells is a biphasic event: integrin very late antigen-4 alpha
      mediates only the early phase of the heterotypic adhesion.
AB  - Heterotypic adherence between marrow stromal cells (MSC) and lymphoblastic cells
      is essential for normal lymphopoiesis and malignant lymphoblastic development.
      However, the detailed molecular mechanisms by which this heterotypic adherence
      occurs are poorly understood. The cell-cell interactions between a B
      lymphoblastic cell line (UTMB-460) and a pre-B-cell line (NALM-6) with MSC were
      chosen as models to investigate potential mechanisms and adhesion molecules
      involved in the apposition between normal and malignant lymphoblastic cells and
      MSC. A parallel-flow detachment assay (PFDA) and a 51Cr detachment assay, coupled
      with monoclonal antibody (MoAb) blocking experiments, were used to quantify the
      attachment of lymphoblastic cells to confluent monolayers of MSC. The apposition
      between MSC and B-lymphoblastic cells (UTMB-460 cells) was investigated for
      variable time periods, ranging from 1 minute to 4 hours. Results from the
      temporal study suggest that the heterotypic adherence of the B-lymphoblastic
      cells to MSC is a biphasic event and the interactions occur rapidly (< or = 1
      minute) after the two cells come into contact. More specifically, the early phase
      of adherence (< or = 15 minutes) solely involves very late antigen-4 alpha (VLA-4
      alpha)/vascular cell adhesion molecule 1 (VCAM-1) interactions, as evidenced by
      the nearly complete inhibition (93%) of UTMB-460 cell adherence in the presence
      of anti-VLA-4 alpha. The late phase (> or = 30 minutes) proceeds despite the
      continuous presence of anti-VLA-4 alpha. In addition, the late-phase adherence is
      not affected by MoAbs to LFA-1, CD44, VCAM-1, E-selectin, or L-selectin, which
      suggests the possible involvement of other adhesion molecules. Adherence of pre-B
      lymphoblastic cells (NALM-6) to MSC is also biphasic. Integrin VLA-4 is again a
      major player in the early phase of pre-B-lymphoblastic cell/MSC interactions. The
      early phase of adherence may be important in homing of the malignant
      lymphoblastic cells to the MSC and the late phase in retention of malignant
      lymphoblastic cells in the bone marrow.

PMID- 7528567
TI  - Proliferation and differentiation of myelodysplastic CD34+ cells: phenotypic
      subpopulations of marrow CD34+ cells.
AB  - In a search for a mechanism to explain the impaired growth of progenitor cells in
      patients with myelodysplastic syndromes (MDS), marrow CD34+ cells were purified
      up to 94.9% +/- 4.2% for normal individuals and 88.1% +/- 17.6% for MDS patients,
      using monoclonal antibodies and immunomagnetic microspheres (MDS CD34+ cells).
      Phenotypic subpopulations of these CD34+ cells were analyzed for CD38, HLA-DR,
      CD33, CD13, CD14, CD41 and CD3 plus CD19, in association with proliferative and
      differentiative capacities. The 15 studies performed included 12 MDS patients.
      Coexpression rate of CD13 significantly increased in the MDS CD34+ cell
      population with a value of 91.4% +/- 11.6% and ranging from 60.3% to 100%, and
      exceeded 99% in four studies, whereas that of normal CD34+ cells was 49.9% +/-
      15.8%, ranging from 28.2% to 70.1% (P < .001). Coexpression rate of CD38, HLA-DR,
      CD33, CD14, and CD3 plus CD19 in MDS CD34+ cells did not significantly differ
      from that of normal CD34+ cells. The total number of colonies and clusters grown
      from 100 normal marrow CD34+ cells was 40.4 +/- 8.6, the range being from 27.2 to
      50.3; this varied in MDS marrow CD34+ cells with a value of 34.0 +/- 28.7, the
      range being 0 to 95.9. The lineage of colonies and clusters promoted by MDS
      marrow CD34+ cells was predominantly committed to nonerythroid with impaired
      differentiation in 13 of 15 studies (87%). CD13 is first expressed during
      hematopoiesis by colony-forming unit granulocyte-macrophage and is absent in
      erythroid progenitors. Therefore, this study provides direct evidence for the
      lineage commitment of MDS CD34+ cells to nonerythroid with impaired
      differentiation and explains the mechanism of nil or low colony expression of MDS
      progenitor cells to erythroid lineage.

PMID- 7528563
TI  - Lectin and epidermal growth factor domains of P-selectin at physiologic density
      are the recognition unit for leukocyte binding.
AB  - P-selectin is an integral membrane glycoprotein on stimulated platelets and
      endothelial cells that serves as a receptor for leukocytes. To estimate the
      density of P-selectin in membranes necessary to support adhesion, we incorporated
      purified P-selectin at varying concentrations into phospholipid bilayers that
      encapsulated glass microspheres. Maximal binding of these lipospheres to HL60
      cells, a P-selectin ligand-expressing cell line, was approached at a P-selectin
      density of about 100 molecules per microns 2; half-maximal binding was observed
      at about 50 to 60 molecules per microns 2. Compatible results were obtained with
      P-selectin expressed on Chinese hamster ovary cells. The P-selectin density on
      stimulated platelets was estimated to be 150 to 200 molecules/microns 2. To
      identify the domains of P-selectin required for HL60 cell binding, chimeras of P
      selectin and L-selectin were stably expressed in Chinese hamster ovary cells and
      clones that expressed the chimeras at the estimated physiologic density were
      selected. Chimeras containing the P-selectin lectin and epidermal growth factor
      (EGF) domains or the lectin, EGF, and short consensus repeats bound HL60 cells
      equivalently, but a chimera containing the P-selectin lectin domain alone bound
      HL60 cells much less well. These results indicate that at a physiologically
      relevant P-selectin density on membrane surfaces, the lectin, and EGF domains of
      P-selectin are together required for optimal leukocyte binding.

PMID- 7528568
TI  - Induction of differentiation of WEHI-3B D+ leukemic cells transfected with
      differentiation-stimulating factor/leukemia inhibitory factor receptor cDNA.
AB  - Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor can
      induce the differentiation of mouse myeloid leukemia M1 cells and also stimulate
      proliferation of the interleukin-3 (IL-3)-dependent cell line, DA-1a. To
      determine whether D-factor can induce the differentiation of leukemia cells other
      than M1 cells, WEHI-3B D+ mouse myelomonocytic leukemia cells were transfected
      with a plasmid containing mouse D-factor receptor cDNA. Expression of D-factor
      receptor in transfected cells was determined by binding of [125]D-factor and
      analyzed by Scatchard's method. The transfected cells had high-affinity D-factor
      receptors with a dissociation constant of 100 to 200 pmol/L and binding sites per
      cell varied from 67 to 1,500 among several clones. The cells expressing a high
      level of D-factor receptor were induced to differentiate by D-factor; about 60%
      of the cells exhibited the ability to reduce nitroblue tetrazolium and expression
      of the differentiation antigen Mac-1 (CD11b) on the cell surface increased. The
      effect of cytokines, which induce the differentiation of M1 cells, on the
      transfected WEHI-3B cells was examined. The sensitivity to oncostatin M was
      identical to that against D-factor in the cells of each clone. Expression of D
      factor receptor in WEHI-3B cells promoted sensitivity to IL-6 and granulocyte
      colony-stimulating factor (G-CSF). Induction of differentiation of the cells
      accompanied the suppression of proliferation. Treatment of the cells with D
      factor for longer than 5 days resulted in 50% inhibition of growth. These results
      indicate that the stimulating effect of D-factor on the differentiation of
      malignant myeloid cells is not unique to M1 cells.

PMID- 7528569
TI  - Sickle reticulocytes adhere to VCAM-1.
AB  - Adherence of sickle (SS) erythrocytes to endothelial cells represents
      interactions between red blood cell (RBC) and endothelial cell surface molecules.
      To enhance our understanding of the ligands involved, we transfected COS cells
      with the cDNAs of two endothelial cell adhesion molecules, VCAM-1 and E-selectin,
      and measured the binding of normal and sickle RBCs after static incubation. The
      percentage of COS cells with rosettes (five or more adherent RBCs) was
      determined. Normal RBCs did not adhere to VCAM-1-transfected COS cells.
      Unfractionated SS RBCs formed rosettes on the VCAM-1-transfected COS cells (mean
      +/- SD, 5.85% +/- 4.98%). Low-density SS RBCs were more adherent than high
      density SS RBCs (P < .005). The adherent SS RBCs were a young reticulocyte
      population, staining positively for transferrin receptor. Another measure of
      reticulocyte age, RNA content, also correlated with adherence. SS RBC binding was
      specific--inhibitable by antibodies to either VCAM-1 or the alpha 4 integrin
      chain of VLA-4. In contrast, there was no significant adherence of normal or SS
      RBCs to E-selectin-transfected COS cells. These results suggest that young
      reticulocytes bind to endothelial cell VCAM-1 via VLA-4 integrin.

PMID- 7528571
TI  - Antibodies cross-reactive with E- and P-selectin block both E- and P-selectin
      functions.
AB  - E- and P-selectin are inflammation-induced cell adhesion molecules that mediate
      leukocyte-endothelial cell and leukocyte-platelet interactions. Monoclonal
      antibodies (MoAbs) specific for either E-selectin or P-selectin are protective in
      several animal models of inflammatory disease. To generate an MoAb with broader
      therapeutic potential, MoAbs that bind to both E- and P-selectin were generated
      by immunization of mice with mouse pre-B cell lines transfected with human E- and
      P-selectin. Interestingly, although the only selection criterion was the ability
      to bind both E- and P-selectin, all three antibodies obtained efficiently block
      both E- and P-selectin-mediated functions. The inhibited functions include
      neutrophil or HL-60 cell binding to tumor necrosis factor-alpha-activated human
      umbilical vein endothelial cells, E- or P-selectin transfectant cell lines, and
      platelet-HL-60 rosetting. These antibodies, EP-5C7, EP-2C9, and EP-1D8, recognize
      the same or overlapping epitope within the lectin domains of E- and P-selectin.
      The data suggest that functionally important epitopes of homologous proteins can
      be targeted by selecting for antibodies with reactivity toward both proteins.
      Furthermore, a potent blocking antibody specific for both E- and P-selectin may
      provide a more effective and broadly useful reagent for treating acute and
      potentially certain chronic inflammatory conditions.

PMID- 7528570
TI  - Harvesting and enrichment of hematopoietic progenitor cells mobilized into the
      peripheral blood of normal donors by granulocyte-macrophage colony-stimulating
      factor (GM-CSF) or G-CSF: potential role in allogeneic marrow transplantation.
AB  - To explore the use of stem/progenitor cells from peripheral blood (PB) for
      allogeneic transplantation, we have studied the mobilization of progenitor cells
      in normal donors by growth factors. Normal subjects were administered either
      granulocyte-macrophage colony-stimulating factor (GM-CSF) at 10 micrograms/kg/d,
      or G-CSF at 10 micrograms/kg/d, or a combination of G- and GM-CSF at 5
      micrograms/kg/d each, administered subcutaneously for 4 days, followed by
      leukapheresis on day 5. Mononuclear cells expressing CD34 (CD34+ cells) were
      selectively enriched by affinity labeling using Dynal paramagnetic microspheres
      (Baxter Isolex; Baxter Healthcare Corp, Santa Ana, CA). The baseline CD34+ cells
      in peripheral blood before mobilization was 0.07% +/- 0.05% (1.6 +/- 0.7/microL;
      n = 18). On the fifth day after stimulation (24 hours after the fourth dose), the
      CD34+ cells were 0.99% +/- 0.40% (61 +/- 14/microL) for the 8 subjects treated
      with G-CSF, 0.25% +/- 0.25% (3 +/- 3/microL, both P < .01 v G-CSF) for the 5
      subjects administered GM-CSF, and for the 5 subjects treated with G- and GM-CSF,
      0.65% +/- 0.28% (41 +/- 18/microL, P < .5 v GM-CSF). Parallel to this increase in
      CD34+ cells, clonogenic assays showed a corresponding increase in CFU-GM and BFU
      E. The total number of CD34+ cells collected from the G-CSF group during a 3-hour
      apheresis was 119 +/- 65 x 10(6) and was not significantly different from that
      collected from the group treated with G- and GM-CSF (101 +/- 35 x 10(6) cells),
      but both were greater than that from the group treated with GM-CSF (12.6 +/- 6.1
      x 10(6); P < .01 for both comparisons). Analysis of the CD34+ subsets showed that
      a significantly higher percentage of cells with the CD34+/CD38- phenotype is
      found after mobilization with G- and GM-CSF. In the G-CSF group, immunomagnetic
      selection of CD34+ cells permitted the enrichment of the CD34+ cells in the
      apheresis product to 81% +/- 11%, with a 48% +/- 12% yield and to a purity of 77%
      +/- 21% with a 51% +/- 15% recovery in the G- and GM-CSF group. T cells were
      depleted from a mean of 4.5 +/- 2.0 x 10(9) to 4.3 +/- 5.2 x 10(6) after
      selection, representing 99.9% depletion. We conclude that it is feasible to
      collect sufficient numbers of PB progenitor cells from normal donors with one to
      two leukapheresis procedures for allogeneic transplantation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7528572
TI  - Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical
      trial.
AB  - Butyrate analogues have been shown to increase fetal hemoglobin (HbF) production
      in vitro and in vivo. Sodium phenylbutyrate (SPB), an oral agent used to treat
      individuals with urea-cycle disorders, has been shown to increase HbF in
      nonanemic individuals and in individuals with sickle cell disease. We have
      treated eleven patients with homozygous beta thalassemia (three transfusion
      dependent) and one sickle-beta-thalassemia patient with 20 g/d (forty 500-mg
      tablets) of SPB for 41 to 460 days. All patients showed an increase in the
      percent of F reticulocytes associated with treatment, but only four patients
      responded by increasing their Hb levels by greater than 1 g/dL (mean increase,
      2.1 g/dL; range, 1.2 to 2.8 g/dL). None of the transfusion-dependent thalassemia
      subjects responded. Increase in Hb was associated with an increase in red blood
      cell number (mean increase, 0.62 x 10(12)/L), and mean corpuscular volume (mean
      increase, 6 fL). Changes in percent HbF, absolute HbF levels, or alpha- to non
      alpha-globin ratios as measured by levels of mRNA and globin protein in
      peripheral blood did not correlate with response to treatment. Response to
      treatment was not associated with the type of beta-globin mutation, but baseline
      erythropoietin levels of greater than 120 mU/mL was seen in all responders and
      only two of eight nonresponders to SPB. Compliance with treatment was greater
      than 90% as measured by pill counts. Side effects of the drug included weight
      gain and/or edema caused by increase salt load in 2/12, transient epigastric
      discomfort in 7/12, and abnormal body odor in 3/12 subjects. Two splenectomized
      patients who were not on prophylactic antibiotics developed sepsis while on
      treatment. We conclude that SPB increases Hb in some patients with thalassemia,
      but the precise mechanism of action is unknown.

PMID- 7528573
TI  - Cofactors are essential for stem cell factor-dependent growth and maturation of
      mast cell progenitors: comparative effects of interleukin-3 (IL-3), IL-4, IL-10,
      and fibroblasts.
AB  - Stem cell factor (SCF) possesses many mast cell-stimulating activities, including
      the ability to support the growth of mucosal-like mast cells (MMCs) and
      connective tissue mast cells (CTMCs). However, this study shows that, in the
      absence of accessory cells, SCF does not stimulate the clonal growth of primitive
      mast cell progenitors. Nevertheless, SCF exhibited potent growth-promoting
      effects when combined with the cytokines interleukin-3 (IL-3), interleukin-4 (IL
      4), and interleukin-10 (IL-10). Our comparative studies have shown that optimal
      mast cell colony formation occurs when both IL-4 and IL-10 are combined with SCF.
      However, in the presence of SCF, these two cofactors appear to mediate different
      effects. IL-4 was more efficient than IL-10 in costimulating the initiation of
      SCF-dependent colony formation by mast cell progenitors and in sustaining the
      proliferation of newly generated progeny. On the other hand, IL-4 was less
      efficient than IL-10 in supporting mast cell differentiation, as evidenced by
      morphology, cell enlargement, and granule production. Although the actions of IL
      4 and IL-10 were not equivalent, additional experiments indicated that their
      ability to serve as early- and late-acting factors, respectively, were
      complimentary. We have also found that the mast cells generated in colonies
      stimulated by IL-4, IL-10, and SCF produced high levels of histamine (6-8 pg per
      cell). None of the mast cells generated in our cultures synthesized heparin. A
      phenotypic change from safranin-negative to safranin-positive cells associated
      with heparin-producing CTMCs was accomplished after coculture of the mast cells
      with fibroblast cell lines derived from normal mice or from SI/SId mice plus
      soluble factors. Collectively, our observations demonstrate that SCF acts as a
      competence factor for mast cell progenitor growth. In addition, the ability of
      SCF to support certain stages of mast cell differentiation is profoundly
      influenced by interactions with specific cofactors.

PMID- 7528574
TI  - Soluble kit receptor in human serum.
AB  - c-kit encodes the transmembrane receptor tyrosine kinase (Kit) for the recently
      described ligand stem cell factor (SCF). We have developed an enzyme-linked
      immunosorbent assay for measuring soluble human Kit and we have used the assay to
      show high levels of soluble Kit in human serum. The distribution of soluble Kit
      levels was investigated among 112 normal human serum donors. The mean serum level
      (+/- SD) was found to be 324 +/- 105 ng/mL with the values falling between 163
      ng/mL and 788 ng/mL. No correlation between soluble Kit levels and the sexes or
      ages of the donors was found. Partial purification using immunoaffinity
      chromatography allowed us to characterize the soluble Kit from pooled human
      serum. Antibodies generated to a 497-amino acid recombinant human soluble Kit
      corresponding to the N-terminal extracellular domain of the receptor recognized
      the serum-derived soluble Kit by immunoblotting. We found that the serum-derived
      soluble Kit is glycosylated, with mostly N-linked but also O-linked carbohydrate,
      and with terminal sialic acid residues. When compared with the recombinant human
      soluble Kit, the serum-derived material was similar both in size and
      glycosylation pattern. CNBr cleavage of the isolated serum-derived material
      followed by amino terminal sequencing confirmed the presence of five peptides
      expected for the extracellular portion of the Kit molecule. The immunoaffinity
      purified serum-derived soluble Kit inhibited binding of [125I]SCF to membrane
      bound receptor in an in vitro assay. These results indicate that soluble Kit
      could modulate the activity and functions of SCF in vivo.

PMID- 7528575
TI  - Long-term treatment of canine cyclic hematopoiesis with recombinant canine stem
      cell factor.
AB  - Grey collie dogs have cyclic fluctuations in their blood cell counts caused by a
      regulatory defect of hematopoietic stem cells. To examine the role of stem cell
      factor (SCF) or its receptor in this disorder, we investigated the stimulatory
      effects of recombinant canine SCF (rc-SCF) on in vitro marrow cultures, cloned
      and sequenced the grey collie SCF gene, and treated three grey collies with rc
      SCF, either alone or in combination with recombinant canine granulocyte colony
      stimulating factor (rcG-CSF). Colony-forming unit granulocyte-macrophage
      formation from grey collie or normal dog marrow showed similar dose-response
      curves for rc-SCF. Cloning and sequencing the SCF gene for two grey collies
      showed no evidence of mutations in the coding region of the SCF gene. Treatment
      with rc-SCF (10 to 100 micrograms/kg/d) did not induce neutrophilia except at the
      highest dose (100 micrograms/kg/d), but daily rc-SCF abrogated the neutropenic
      periods in doses of 20 micrograms/kg/d or greater. Combination of rc-G-CSF (0.5
      to 1.0 microgram/kg/d) with rc-SCF treatment (20 to 50 micrograms/kg/d) suggested
      a synergistic effect, ie, the neutrophil levels on combined therapy were higher
      than the sum of the levels when these two cytokines were given separately. Long
      term treatment of these dogs with rc-SCF in doses of 10 to 30 micrograms/kg/d was
      generally well tolerated, suggesting that SCF may be useful as a therapy for some
      chronic hypoproliferative disorders of hematopoiesis.

PMID- 7528576
TI  - Granulocyte-macrophage colony-stimulating factor expression by human fibroblasts
      is both upregulated and subsequently downregulated by interleukin-1.
AB  - Interleukin-1 (IL-1) treatment of human WI-38 lung fibroblasts results in
      granulocyte-macrophage colony-stimulating factor (GM-CSF) expression as well as a
      delayed increase in prostaglandin E2 (PGE2) production that closely correlates
      with the decline of GM-CSF mRNA levels. Pretreatment with PGE2 reduces the IL-1
      induced GM-CSF mRNA and protein expression to 10% to 15% of control values at
      concentrations of PGE2 that are endogenously produced after IL-1 stimulation.
      Inhibition of PGE2 synthesis by indomethacin prolongs the IL-1 induced GM-CSF
      mRNA expression and increases the cumulative GM-CSF protein secretion. Exposure
      of WI-38 fibroblasts to PGE2 results in an increase in intracellular cyclic
      adenosine monophosphate (cAMP) levels. The inhibition of GM-CSF expression by
      PGE2 can be mimicked by stable cAMP analogs as well as cAMP elevating agents such
      as cholera toxin, forskolin, and isobutylmethylxanthine. Thus the inhibition
      exerted by PGE2 is mediated via cAMP. Taken together, these results suggest that
      IL-1 stimulation of human fibroblasts provides not only the upregulatory signal
      for GM-CSF expression but also a delayed and indirect downregulatory signal that
      serves to limit GM-CSF expression in the continued presence of IL-1.

PMID- 7528579
TI  - Cloning and sequencing of an ovine granulocyte colony-stimulating factor cDNA.
AB  - A cDNA encoding an ovine (ov) granulocyte colony-stimulating factor (G-CSF) was
      cloned by polymerase chain reaction, using primers based on the 5' and 3'
      nucleotide (nt) sequence of the bovine (bov) G-CSF cDNA. RNA was isolated from
      IFN-gamma and LPS-stimulated alveolar macrophages. The isolated ovG-CSF cDNA is
      522 bp in length and does not include coding sequence for a secretory signal
      peptide. The nt sequence is 95% identical to the bovG-CSF nt sequence, and
      includes conservation of 5 cysteine residues. The deduced amino acid (aa)
      sequence of the mature ovG-CSF protein shares 96%, 82% and 68% homology with the
      bov, human and murine mature G-CSF proteins, respectively. The estimated
      molecular weight of the 174 aa G-CSF protein is 18.8 kilodaltons.

PMID- 7528578
TI  - The sialomucin CD34 is expressed on hematopoietic cells and blood vessels during
      murine development.
AB  - The processes of angiogenesis and hematopoiesis require a high degree of
      coordination during embryogenesis. Whereas much is understood about the
      development of the vascular system in avian embryos, little information has been
      attained in mammals, predominantly because there are no specific markers for
      either blood vessels or hematopoietic cells in any developing mammalian system.
      We have recently shown that murine CD34 (mCD34) is expressed on the vascular
      endothelium in all organs and tissues of the adult mouse as well as on a small
      percentage of presumably hematopoietic stem cells in the bone marrow and fetal
      liver. Here we show that mCD34 is also expressed on the endothelium of blood
      vessels and on a subset of hematopoietic-like cells throughout murine
      development. mCD34 is first observed on the yolk sac endothelium of day 7.5
      embryos and on a subset of hematopoietic cells within these yolk sacs. mCD34
      expression is maintained on vessels and hematopoietic cells in all organs and
      tissues throughout embryogenesis. In addition, mCD34 is localized on growth
      conelike filopodial processes that appear at the budding edge of newly sprouted
      capillaries. Double staining of capillaries for mCD34 and laminin shows that
      these growth conelike processes seem to be free of laminin, whereas the formed
      capillaries seem to be coated with this extracellular matrix protein. Analysis of
      vessels in developing brain shows that these filopodial processes seem to be
      directed toward the ventricular epithelium, a previously described site of
      vascular endothelial growth factor synthesis. Finally, we show that the vascular
      structures of developing murine embryoid bodies also express mCD34. These data
      suggest that mCD34 is a useful marker for the analysis of the development of the
      blood vascular system in murine embryos.

PMID- 7528580
TI  - Demethylation in the 5'-flanking region of mouse cellular retinoic acid binding
      protein-I gene is associated with its high level of expression in mouse embryos
      and facilitates its induction by retinoic acid in P19 embryonal carcinoma cells.
AB  - The mouse cellular retinoic acid binding protein-I (CRABP-I) gene is specifically
      up-regulated by retinoic acid (RA) in P19 mouse embryonal carcinoma cells, and
      its expression in animals is spatially and temporally restricted to RA-sensitive
      tissues during embryonic development. This study demonstrates that, in adult
      mouse tissues and P19 cells where the expression of CRABP-I is detected at the
      basal level, the 5'-flanking region of the CRABP-I gene is hypermethylated at the
      C residues of all the Hpa II sites. Conversely, in mouse embryos during early
      stages of development when the expression of CRABP-I gene is detected at a much
      higher level, this region is demethylated at these Hpa II sites. In P19,
      enhancement on the RA-induced up-regulation of CRABP-I can be observed in cells
      treated with 5-azacytidine (5-AzaC) in conjunction with RA, where partial
      demethylation in the 5'-flanking region of CRABP-I gene is observed. Nuclear run
      on experiments indicate that increased message levels of CRABP-I in P19 cells can
      be accounted for, at least partially, by increases in its transcription rates.
      The induction of retinoic acid receptor (RAR) beta by RA can also be enhanced by
      5-AzaC, but to a much lesser degree. In contrast, all the Hpa II sites in the
      structural gene portion, at least in the first two exons, are fully demethylated
      at the C residues.

PMID- 7528581
TI  - Serogroup-specific and serogroup-cross-reactive epitopes of Legionella
      pneumophila.
AB  - A panel of monoclonal antibodies was used to serotype 343 Legionella pneumophila
      isolates, using the indirect immunofluorescence test and ELISA. In addition, the
      isolates were typed by means of absorbed rabbit antisera to provide a reference
      procedure. As shown by a comparison of reaction patterns, serogroup-specific
      monoclonal antibodies were found for serogroups 1, 2, 3, 4, 6, 7, 8, and 10.
      Monoclonal subtypes were found to exist within serogroups 1, 2, 5, and 6. Using
      the monoclonal antibody panel introduced for serogroups 1 to 8 and 10, it was
      possible to serotype or subtype 92% of the isolates tested. The remaining
      isolates belonged to serogroups 9, 11 to 14 and to a monoclonal subtype of
      serogroup 5. 8 monoclonal antibodies recognized serogroup-cross-reactive
      epitopes. Except for serogroups 1, 7, and 11, all others shared a common
      antigenic determinant. Another common epitope was shared by strains of serogroups
      2 and 3. Additional cross-reactivity was associated in particular with strains of
      serogroups 5, 8, and 10.

PMID- 7528577
TI  - Hematopoietic cell phosphatase associates with erythropoietin (Epo) receptor
      after Epo-induced receptor tyrosine phosphorylation: identification of potential
      binding sites.
AB  - Erythropoietin (Epo) binding to its receptor (EpoR) induces tyrosine
      phosphorylation in responsive cells and this ability is required for a mitogenic
      response. One of the substrates of tyrosine phosphorylation is the Epo receptor
      (EpoR). The carboxyl region of EpoR cytoplasmic domain is required for EpoR
      phosphorylation and has been shown to negatively affect the response to Epo both
      in vivo and in cell lines. Hematopoietic cell phosphatase (HCP) has also been
      hypothesized to negatively regulate erythropoiesis, based on the hypersensitivity
      to Epo of erythroid lineage cells in moth-eaten mice that genetically lack HCP.
      In the studies presented here, we show that HCP binds the tyrosine phosphorylated
      Epo receptor through the amino-terminal src-homology 2 (SH2) domain of HCP. Using
      a series of phosphotyrosine-containing peptides, potential HCP binding sites in
      the cytoplasmic domain of the EpoR are identified. The results support the
      concept that, after Epo stimulation, phosphorylation of EpoR provides a docking
      site for HCP in the receptor complex. Recruitment of HCP to the complex and its
      subsequent dephosphorylation of substrates and/or associated kinases may be
      important to mitigate the ligand-induced mitogenic response.

PMID- 7528582
TI  - [Early indications for partial learning disorders--anamnestic and diagnostic
      strategies].
AB  - A surprisingly small amount of information exists about early symptoms of
      learning disorders becoming evident during the first years at school. Only one
      relation seems to carry some degree of reliability: Early language deficits
      and/or retardation of language acquisition and later learning disorders including
      dyslexia. Because of these limitations, a more pragmatic approach is recommended.
      Questionnaires can be used asking for specific and age-related skills, involving
      the existence and good functioning of strategically working and concept-building
      central structures. Children with deficits in these structures will develop and
      experience dysfunctions in their cognitive, social and motor abilities.
      Consequently, they present behavioural problems. Children whose questionnaires
      offer suspicion in respect of specific dysfunctions should be tested by means of
      structured play tests or by appropriate developmental tests, to determine their
      individual patterns of talents and specific shortcomings. An early therapeutic
      intervention, aimed at the child's specific and individual deficits, may prevent
      or reduce learning problems at school.

PMID- 7528583
TI  - Antibody to hepatitis C virus in volunteer blood donors of the Hospital de
      Especialidades, National Medical Center, Mexico City.
AB  - The present survey was performed to assess the hepatitis C virus seroprevalence
      in volunteer blood donors of the National Medical Center, Hospital de
      Especialidades, Mexico City. Serum samples from 1100 individuals were collected.
      We selected second generation enzyme-linked immunosorbent assay (ELISA) (Abbott
      HCV EIA) test for the screening. The antibodies against hepatitis C virus (anti
      HCV) in the volunteer blood donors were positive in 0.7%. The second generation
      ELISA test is useful as a screening test and may lead to decreasing the incidence
      of posttransfusional hepatitis C virus infection.

PMID- 7528584
TI  - Effects of hypertonic saline hydroxyethyl starch solution on collagen-induced
      platelet aggregation and ATP secretion.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of hypertonic
      (NaCl 7.5%) hydroxyethyl starch (HES 6%, molecular weight 200,000) (HHES) as used
      for small-volume resuscitation on global coagulation parameters and platelet
      function. DESIGN: Randomized, controlled clinical trial. SETTING: Intraoperative
      volume loading after induction of general anesthesia. PATIENTS: 27 consecutive
      patients [mean age 59 (22-76) years, mean body weight 69.8 (46-98) kg] undergoing
      abdominal surgery were studied. INTERVENTIONS: Global coagulation tests (aPTT:
      activated partial thromboplastin time; PT: prothrombin time; platelet count;
      thrombelastography: TEG), platelet aggregation and ATP release were measured
      before and 10 min after the application of 4 ml.kg-1 of HHES (study group H, n =
      14) or HES (control group C, n = 13). RESULTS: The aPTT was prolonged and
      platelet count was significantly reduced in both study groups. In contrast to the
      HES group, clot formation time in the TEG was significantly prolonged and the
      maximum amplitude was reduced in the HHES group. Furthermore, platelet
      aggregation was significantly slowed down, whereas ATP release significantly
      increased in the HHES group. CONCLUSION: The changes in global coagulation
      parameters can be explained by dilutional effects of the infused solution. The
      hyperosmolar saline compound of the HHES solution obviously contributes to the
      slowing down of platelet aggregation. Osmotic stress and membrane pleating may
      aggravate HES-induced changes in membrane fluidity and microviscosity and thus
      explain this impaired interaction. The increase in ATP release suggests a change
      in receptor-second messenger interaction for delta granule release.

PMID- 7528585
TI  - [The relationship between the components of leukocyte peroxisomes and nitric
      oxide generation].

PMID- 7528587
TI  - Indocyanine green video angiography in patients with age-related maculopathy
      related retinal pigment epithelial detachments.
AB  - Previous studies have stressed the benefit of laser photocoagulation for patients
      with age-related macular degeneration (AMD) and well-defined subretinal
      neovascularization (SRN). However, such lesions account for only 30% of cases
      with exudative age-related maculopathy. Especially in patients with retinal
      pigment epithelial detachment (PED), SRN is usually occult. This study was
      performed to reveal the role of digital indocyanine green (ICG) video angiography
      in the diagnosis of SRN in patients with PED. A total of 34 patients with AMD
      associated retinal PED participated in the current study and underwent
      fluorescein and ICG angiography using scanning laser ophthalmoscopy. In these
      patients fluorescein angiography revealed no distinct SRN, whereas in 21 eyes
      (62%) ICG angiography showed well-demarcated choroidal neovascularization. The
      present study demonstrates that SRN can be detected in more than 50% of patients
      with PED by means of ICG video angiography. Therefore, ICG video angiography
      improves the detection of SRN in patients with AMD-associated PED.

PMID- 7528586
TI  - Isolation and characterization of two new N-glycosidase type-1 ribosome
      inactivating proteins, unrelated in amino-acid sequence, from Petrocoptis
      species.
AB  - Two new N-glycosidase type-1 ribosome-inactivating proteins (RIPs), denoted
      petroglaucin 1 and petrograndin, respectively, were isolated from the plants
      Petrocoptis glaucifolia (Lag.) Boiss sp. viscosa (Rothm.) Lainz and Petrocoptis
      grandiflora Rothm. These new RIPs do not share H2N-terminal amino-acid sequence
      homology with petroglaucin (now denoted as petroglaucin 2), the only other type-1
      RIP to be isolated from P. glaucifolia (Arias et al. (1992) Planta 186, 532-540).
      Petroglaucin 1 shares amino-acid sequence homology with RIPs from Cucurbitaceae
      while petroglaucin 2 and petrograndin do so with saporins and dianthin 30
      (Caryophyllaceae). The new RIPs strongly inhibited protein synthesis at
      subnanomolar concentrations in rabbit reticulocyte lysates and other eukaryotic
      cell-free systems, but they were inactive on bacterial ribosomes.

PMID- 7528589
TI  - Can human hematopoietic stem cells be cultured ex vivo?
AB  - The factors that induce proliferation of the human hematopoietic stem cell are
      ill defined. Further characterization of such growth factors will be needed to
      develop ex vivo culture systems that induce prolonged proliferation and expansion
      of human hematopoietic stem cells. Human or murine hematopoietic progenitors that
      can initiate and sustain long-term culture systems (LTC-IC) represent a
      population of very primitive hematopoietic progenitors. When cultured in direct
      contact with stromal layers, we and others have demonstrated that a fraction of
      such LTC-IC can be maintained. In addition, stroma-free long-term cultures
      supplemented with two to nine cytokines can induce proliferation and
      differentiation of immature human hematopoietic progenitors. However, 70-90% of
      primitive LTC-IC are lost after five weeks in such cultures. We describe a
      "stroma-non-contact" culture system, in which progenitors are cultured separated
      from stroma by a 0.4 micron microporous membrane which prevents cell stroma
      contact but allows free passage of diffusible factors. Primitive progenitors in
      such cultures can not only differentiate into committed progenitors but also are
      maintained to a greater extent than in Dexter cultures. We will discuss the
      relative contribution of 1) direct contact between hematopoietic progenitors and
      bone marrow stroma, 2) soluble stroma-derived factors and 3) previously
      characterized growth promoting and presumed growth inhibitory cytokines in the in
      vitro maintenance and potential expansion of LTC-IC.

PMID- 7528588
TI  - A family of ligands for the TNF receptor superfamily.
AB  - Recent progress in the definition of molecules involved in immune regulation has
      led to the discovery of a number of type I membrane glycoproteins with a
      distinctive, cysteine-rich, repetitive domain structure within their
      extracellular regions. Because the prototype members of this family are receptors
      for cytokines (tumor necrosis factor [TNF] and nerve growth factor [NGF]), it was
      expected that the ligands for the other receptors would possess cytokine-like
      activities. This prediction has been fulfilled by the cloning of cDNA encoding a
      series of type II membrane glycoproteins, with homology to TNF, that bind to, and
      signal through, their cognate receptors. While the biological role of some of
      these ligand-receptor pairs remains obscure, at least two members of the family,
      CD40 and Fas, have proven their importance. The human X-linked immunodeficiency,
      hyper IgM syndrome, is the result of mutations in the CD40 ligand gene, and the
      Fas and Fas ligand genes are mutated in two mouse strains, lpr and gld, that
      develop autoimmune disease. These findings, together with other evidence, point
      to key roles of CD40/CD40 ligand interactions in immune activation, particularly
      in T-dependent B cell responses, and of Fas/Fas ligand in apoptosis and
      peripheral tolerance. These molecules, as well as the other ligands of the
      family, share the property of costimulation of T cell proliferation and are all
      expressed by activated T cells. More detailed analysis of the expression patterns
      of ligands and receptors on lymphocyte subpopulations will be necessary to define
      their different roles in immune activation and suppression.

PMID- 7528590
TI  - Enrichment and characterization of peripheral blood-derived megakaryocyte
      progenitors that mature in short-term liquid culture.
AB  - A population of peripheral blood-derived cells that mature into megakaryocytes
      within four to eight days of liquid culture is described. This population was
      enriched from normal leukapheresis units by counterflow centrifugal elutriation
      and CD34 selection. The cells were incubated in suspension with known
      megakaryocyte growth or maturation factors. Megakaryocytes were identified within
      the cultures with antibodies to platelet-glycoproteins (Ib and IIb) and
      cytologically classified as stage I-IV cells. Plasma from aplastic dogs (APK9) or
      human recombinant interleukin 3 (IL-3) were the only culture additives which
      reproducibly resulted in megakaryocyte development. The activity present in APK9
      was relatively megakaryocyte-specific while IL-3 was not. The phenotype of the
      short-term megakaryocyte progenitor cell population was determined by FACS and
      found to be CD34bright but not CD34dull or CD34-. The population was further
      characterized as CD34+/CD38+ and CD34+/HLA-DR+. Both CD34+/CD41- and CD34+/CD41+
      populations contained megakaryocyte progenitor cells, although megakaryocytes
      that developed from the latter population were fewer in number. In summary, we
      have developed an enrichment protocol that, when coupled with a liquid culture
      assay system, enabled us to characterize short-term megakaryocyte progenitors
      from peripheral blood. These cells may be important for early platelet recovery
      in transplantation settings.

PMID- 7528591
TI  - Synergy among erythropoietin, interleukin 3, stem cell factor (c-kit ligand) and
      interferon-gamma on early human hematopoiesis.
AB  - The stimulatory effect of interferon-gamma (IFN-gamma) on human early
      hematopoiesis was investigated using CD34+ cells that were purified from
      peripheral blood as a target. In the presence of human interleukin 3 (IL-3) and
      stem cell factor (SCF), the growth of colony forming units for
      granulocyte/macrophage (CFU-GM) in serum-free methylcellulose culture was
      enhanced up to 5.5-fold over baseline colony formation (n = 10, mean +/- SE, 3.18
      +/- 1.00) by coculture with 2.5 x 10(3) U/ml IFN-gamma, whereas burst forming
      units-erythroid (BFU-E) growth induced by additional erythropoietin (Epo) was
      reduced dose-dependently. Liquid-suspension culture of the target cells for 24 h
      with IFN-gamma before secondary plating in serum-free methylcellulose resulted in
      a marked increase in the colony numbers; 3.62 +/- 1.04-fold for CFU-GM and 5.72
      +/- 2.32-fold for BFU-E (n = 5). The effect was most striking in the growth of
      erythroid lineage supported by Epo alone in serum-free culture. Delayed addition
      of IFN-gamma between days 4 and 7 of methylcellulose culture suppressed CFU-GM
      growth, but not that of BFU-E. These results suggest that IFN-gamma is an
      essential cytokine that affects human hematopoiesis and exerts a bimodal effect
      on stem cell maturation; potentiating or replacing the effect of early-acting
      cytokines such as SCF or IL-3, and suppressing the growth of matured progenitor
      cells.

PMID- 7528592
TI  - Human peripheral blood granulocytes and myeloid leukemic cell lines express both
      transcripts encoding for stem cell factor.
AB  - Stem cell factor (SCF), the ligand for the c-kit proto-oncogene, has been shown
      to play a critical role in the migration of melanocytes and germ cells during
      embryogenesis as well as in the proliferative control of the hematopoietic
      compartment. In this study we investigated the expression of both the soluble and
      transmembrane SCF forms in purified peripheral blood populations and in several
      hematopoietic cell lines. Expression of both transcripts, though in different
      ratios, was identified in whole bone marrow, in bone marrow stromal cells and in
      human peripheral blood. In peripheral blood, SCF expression could be ascribable
      to polymorphonuclear leukocytes (PMN), whereas no SCF expression was detected in
      isolated lymphocytes, monocytes and in some T lymphoid cell lines. Conversely,
      some hematopoietic myeloid cell lines, such as HL-60, KG1 and K562, express SCF
      with similar patterns.

PMID- 7528593
TI  - Water channels in membranes.
AB  - A systematic programme of comparative nuclear magnetic resonance measurements of
      the membrane permeability for water (Pd) and of activation energy (Ea,d) of this
      process in red blood cells of various wild, laboratory and domestic animals was
      carried out here. The RBC from humans, cow, sheep and kangaroos had Pd values
      around 5 x 10(-3) cm/s at 25 degrees C, 7 x 10(-3) cm/s at 37 degrees C with Ea,d
      values around 25 kJ/mol. For RBC from other ten marsupial species and from mouse,
      rat and rabbit, the Pd values were more than twice as high as for human RBC. For
      mosr RBC a high value of Pd was associated with a low value of Ea,d (range from
      15 to 21 kJ/mol), pointing to specialized channels for water diffusion
      incorporated in membrane proteins. Recently a channel-forming integral protein of
      28 kDa (CHIP 28) was identified as a major water channel protein in the RBC
      membrane. A procedure for quantitating the purified CHIP 28 by densitometry of
      silver-stained polyacrylamide gel electrophoreograms was developed. The analysis
      of a purified fraction of CHIP 28 showed that the 28 kDa component represents
      approximately two-thirds of the sample with the remainder comprising the
      glycosylated high-molecular-weight component. A correlation between the content
      in CHIP 28 and the relative water permeability among RBC from different
      vertebrate species was attempted.

PMID- 7528594
TI  - Cryptosporidium parvum sporozoites deposit trails of 11A5 antigen during gliding
      locomotion and shed 11A5 antigen during invasion of MDCK cells in vitro.

PMID- 7528595
TI  - Pneumocystis species inferred from analysis of multiple genes.

PMID- 7528596
TI  - Significance of the casein kinase system in cell growth and proliferation with
      emphasis on studies of the androgenic regulation of the prostate.
AB  - Protein phosphorylation is a significant mechanism in many cellular functions,
      including genomic regulation and control of cell proliferation. Thus,
      investigations of protein kinases (PKs) in appropriate experimental models are of
      intense current interest. Employing androgenic regulation of the rat ventral
      prostate (RVP) as an experimental model, we have investigated certain nuclear PK
      reactions with the aim of defining their role in androgen-mediated genomic
      regulation in the prostate and their implications for human prostate
      pathobiology. The author's laboratory identified androgen-sensitive PKs in the
      prostatic cell nucleus that might be involved in regulation of the gland. These
      PKs are analogous to casein kinase 1 (CK-1) and casein kinase 2 (CK-2), which are
      important multipotential enzymes in growth regulation and cell proliferation.
      Because CK-2 demonstrated a greater androgen sensitivity, we investigated the
      mechanism of its regulation at the level of transcription in the RVP, finding
      that androgens exert a substantial tissue-specific effect on its expression.
      However, regulation of CK-2 gene transcription does not appear to be an early
      event in androgen action, an observation that did not accord with our previous
      documentation of an early androgenic modulation of nuclear CKs in the prostate.
      Studies to uncover alternative mechanisms of regulation of CK-2 yielded a
      potentially important observation that androgenic regulation involves changes in
      the association of the enzyme with subnuclear compartments as an early event in
      its growth control function. Additionally, chromatin preparations from human
      benign prostatic hyperplasia (BPH) demonstrate a large enhancement in intrinsic
      CK-2 activity compared with normal tissue. An increase also is observed in
      specimens of prostatic carcinoma, although the change is less substantial than
      that in BPH. There appears to be a correlation between the localization of CK-2
      in sections of prostatic carcinoma and the Gleason grade, a measure of the degree
      of differentiation. Further investigations of the cellular as well as the
      molecular mechanisms of CK-2 regulation in the prostate as an experimental model
      of the response to influences on growth may yield new insight into the function
      of this PK.

PMID- 7528598
TI  - Penetration and binding of epidermal growth factor-dextran conjugates in
      spheroids of human glioma origin.
AB  - Targeting with toxic EGF-based conjugates against tumour cells with amplified EGF
      receptors might be a possible approach towards improved therapy of certain
      malignancies such as gliomas and squamous carcinomas. In this study, the
      penetration and binding of 125I delivered by EGF-dextran conjugates were analysed
      in cultured spheroids applied as a tumour nodule model. The spheroids consisted
      of human glioma cells, U-343MGaCl2:6, with large amounts of EGF-receptors. The
      penetration and binding patterns of 125I delivered by 125I-EGF and 125I-dextran
      were analysed for comparison. The EGF-dextran associated 125I-activity showed a
      rather slow penetration but after some hours significant amounts of radioactivity
      had reached the deeper regions and good penetration was obtained within 5 hours.
      The penetration seemed somewhat faster when the 125I-activity was delivered with
      EGF possibly dependent on the lower molecular weight allowing for faster
      diffusion. Furthermore, EGF-dextran associated 125I seemed to penetrate somewhat
      faster after the EGF-receptors were blocked with non-radioactive EGF, probably
      due to the lack of binding preventing free diffusion. After administration of
      125I-EGF-dextran or 125I-EGF, the binding patterns were superimposed on the
      penetration patterns. In the penetration studies, the superimposed accumulations
      due to binding were removed by presaturation of the receptors with non
      radioactive EGF. After a 1 hour incubation, binding of EGF-dextran associated
      125I-activity could be seen only in an outer region, with an approximative
      thickness of 50 microns, of the viable cell layer. Extensive receptor specific
      binding in the deeper regions, at a depth of 100-200 microns, was seen after
      several hours incubation. In addition, low levels of non-specific binding in the
      central regions were seen when the 125I-activity was delivered with dextran
      without EGF. A similar low background binding was seen also in the centre of
      spheroids incubated with 125I-EGF-dextran or 125I-EGF after saturation of the
      receptors with non-radioactive EGF. However, the major amount of radioactivity
      delivered as 125I-EGF-dextran or 125I-EGF had a receptor specific binding and,
      also in inner regions, it could be displaced by non-radioactive EGF. Thus, EGF
      dextran, which is a candidate compound for targeted therapy, allowed penetration
      of the applied radioactivity and binding could be observed, after some hours,
      also in the inner regions of the spheroids.

PMID- 7528599
TI  - Binding, internalization and excretion of TGF alpha-dextran associated
      radioactivity in cultured human glioma cells.
AB  - Conjugates based on transforming growth factor alpha, TGF alpha, or epidermal
      growth factor, EGF, are candidates for targeted radiotherapy against EGF-receptor
      rich tumours such as gliomas or squamous carcinomas. In this study, binding,
      internalization and excretion of radiolabelled TGF alpha and TGF alpha-dextran
      conjugates was analysed in an EGF-receptor rich human glioma cell line. The
      binding of 125I-TGF alpha was EGF-receptor specific and the binding pattern was
      similar to that of 125I-EGF. The TGF alpha-dextran conjugate also bound
      specifically but gave maximum binding for a longer time during continuous
      incubation compared to when only TGF alpha was used. The excretion pattern of
      internalized radioactivity was somewhat slower for 125I-TGF alpha-dextran, with
      125I-labelling on the TGF alpha part, as compared to 125I-TGF alpha although most
      of the radioactivity in both cases was excreted within 4 hours. The fate of the
      dextran part of the conjugate, as followed by means of 125I-labelling of the
      dextran, was different since all radioactivity in that case remained cell
      associated for at least up to 22 hours. Furthermore, by comparison with
      previously published results, it was seen that the radioactivity delivered
      through the TGF alpha part of TGF alpha-dextran was retained for a shorter period
      of time by the cells than when delivered by EGF in EGF-dextran conjugates.
      However, when the radioactivity was delivered by the dextran part of the
      conjugates, the radioactivity seemed to be retained equally well or even better
      when TGF alpha-dextran was applied. It is concluded that TGF alpha-dextran, as
      well as EGF-dextran, have interesting properties for targeting against EGF
      receptors and that the dextran part is well retained in the cells and therefore
      might be a suitable carrier for toxic agents such as radionuclides. It is of high
      interest to continue with toxicological and pharmacological in vivo studies of
      the conjugates.

PMID- 7528597
TI  - Hypoxia regulatory elements of the human vascular endothelial growth factor gene.
AB  - Vascular endothelial growth factor (VEGF) expression is highly stimulated by
      hypoxia, both in vitro and in vivo. Recent findings suggest that the VEGF gene
      utilizes an oxygen sensing mechanism similar to the one used by the
      erythropoietin gene. The genomic sequences that control the VEGF response to
      hypoxia are, however, largely unknown. In utilizing transient transfection assays
      in HeLa cells we determined that hypoxia/cobalt responsive enhancer elements are
      present at the 5' and 3' flanking regions of the human VEGF gene. The 3' enhancer
      is contained in a 160 bp fragment located about 60 bp downstream of the
      polyadenylation site. It contains a sequence stretch of about 12 bp which are
      highly homologous to sequences in the erythropoietin hypoxia-responsive enhancer.
      The 5' flanking enhancer is contained in a 100 bp fragment located about 800 bp
      upstream of the start site. This fragment does not contain significant homologies
      with the erythropoietin enhancer. Thus, it appears that the response to hypoxia
      of the VEGF gene is controlled by two regulatory elements; one which may be
      related to the erythropoietin enhancer and a second, which appears to be a
      completely unrelated sequence.

PMID- 7528600
TI  - [Angiogenic role of growth factors].
AB  - Several growth factors are potential inducers of neovascularization. This
      property established from in vitro or in vivo studies suggest that these
      polypeptides might be involved in physiological angiogenesis. Recent advances in
      the structure of the growth factors, identification of specific cell surface
      receptors and in their mechanisms of action bring a better understanding of the
      biochemical events involved in angiogenesis.

PMID- 7528601
TI  - [How tumors abuse their host: the transcription factor c-ets1 and the regulation
      of tumor angiogenesis or invasion].
AB  - During their progression, epithelial tumors induce a stromal reaction essential
      for their development and for metastasis. In situ hybridization studies have
      revealed that the protooncogene c-ets1 is expressed in endothelial cells at the
      beginning tumor angiogenesis, and in stromal fibroblasts surrounding invasive
      tumors. C-ets1 encodes a transcription factor that may activate the transcription
      of genes encoding collagenase 1, stromelysin 1 and urokinase plasminogen
      activator, proteases involved in extracellular matrix degradation. A working
      hypothesis is that c-Ets1 takes part in regulating invasive processes by
      controlling the transcription of these genes. Experimental evidences that may
      confirm this hypothesis will be discussed.

PMID- 7528603
TI  - Changing patterns of infectious diseases.

PMID- 7528602
TI  - Desmopressin for risperidone-induced enuresis.

PMID- 7528604
TI  - Differential expression of cytokeratin proteins during tumour progression in oral
      mucosa.
AB  - The expression pattern of cytokeratin filaments in epithelia has been shown to be
      dependent on their type and grade of differentiation. The type of expression of
      cytokeratin in a cell may also be altered during carcinogenesis or other
      pathological conditions. The present study examined the alterations in expression
      of various cytokeratin types during different stages of tumour progression in the
      oral mucosa. Six monoclonal anti-cytokeratin antibodies were used for the study.
      Conspicuous staining differences with these antibodies were evident between
      normal keratinizing and non-keratinizing mucosa. These differences can be
      correlated to the differentiation pattern of the normal mucosa types. Antibodies
      specific to cytokeratin types 10/11, 19 and 14 showed significant correlation
      with stage of tumour progression. In addition cytokeratin type 18 also showed
      prominent differences in expression between different stages of tumour
      progression. These alterations in cytokeratin expression suggest that the
      terminal differentiation pathway of keratinocytes is disturbed during oral
      carcinogenesis. The results of the present study also emphasize the potential of
      using cytokeratin filaments as markers in the biological staging of oral
      premalignant and malignant lesions.

PMID- 7528605
TI  - Tampering with cytokeratin expression results in cell dysfunction.
AB  - Role of cytokeratins in early embryogenesis in Xenopus and mouse, regeneration of
      liver and keratinization of epithelial cells in adult animals have been worked
      out by manipulating RNA expression as well as protein synthesis using chemical
      modulators, antibodies, antisense DNAs or by transgenic expression. Irrespective
      of the various responses of cells/tissue to the altered keratin network system,
      keratins help in providing architecture and a definite cellular organisation to
      the tissue as a whole, by controlling morphogenetic migration of cells. The role
      of cytokeratins in the morphogenetic movements provides mechanical integrity and
      endurance to the cells.

PMID- 7528609
TI  - Summit builds on co-management concept.

PMID- 7528607
TI  - Serum chromogranin A in the differential diagnosis of Cushing's syndrome.
AB  - We evaluated whether measuring serum levels of chromogranin A, a marker of
      neuroendocrine tumours, could be useful in the differential diagnosis between
      pituitary, adrenal and ectopic causes of Cushing's syndrome. Thirty patients with
      Cushing's syndrome were studied. The localization of the tumours responsible was
      pituitary in 15, adrenal in 5 and ectopic in 10 patients. Serum concentrations of
      chromogranin A were measured in all patients. Petrosal sinus sampling for
      chromogranin A was performed in the cases with pituitary-dependent Cushing's
      syndrome. Immunohistochemical staining for chromogranin A was carried out on part
      of the tumour specimens. Slightly elevated serum levels of chromogranin A (range
      223-262 micrograms/l) were detected in inferior petrosal sinus and peripheral
      venous samples from three patients with pituitary-dependent Cushing's syndrome.
      Serum chromogranin A showed no significant pituitary to peripheral gradient in
      these patients. Chromogranin A levels were not elevated in cases of adrenal
      Cushing's syndrome. Markedly elevated concentrations (range 270-13,900
      micrograms/l) were shown in seven of 10 patients with neuroendocrine tumours with
      ectopic adrenocorticotrophin (ACTH) and/or corticotrophin-releasing hormone (CRH)
      production. Widespread metastasis was present in all these cases. Subjects with
      "occult" carcinoid tumours, with limited spread, had normal chromogranin A
      levels. Immunohistochemical staining for chromogranin A was positive in three out
      of five pituitary adenomas and in all neuroendocrine tumours with ectopic ACTH
      and/or CRH production, while it was negative in all adrenocortical tumour
      specimens. It is concluded that elevated serum levels of chromogranin A can serve
      as markers of neuroendocrine tumours with ectopic ACTH and/or CRH
      production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528606
TI  - Coexistence of choriocarcinoma and hepatoid adenocarcinoma in the stomach.
AB  - The case is presented of a 46 year old woman who had a gastric tumor with
      components of choriocarcinoma, hepatoid adenocarcinoma and common types of
      adenocarcinoma. Although two histologic types of tumor producing carcinoplacental
      or carcinofetal proteins were contained within the tumor, immunohistochemical
      analyses, especially of placental alkaline phosphatase, clearly showed that each
      component was present separately within the same tumor. It was only hepatoid
      adenocarcinoma cells that permeated the lymph and blood vessels. After the
      recurrence, the serum level of alpha-fetoprotein (AFP) markedly elevated, but
      that of human chorionic gonadotropic beta-subunit (hCG-beta) was always within
      normal range. These findings indicate that in the present case the hepatoid
      adenocarcinoma component was more aggressive in growth than the choriocarcinoma
      component.

PMID- 7528611
TI  - Prostaglandin E2 production after lamellar keratectomy and photorefractive
      keratectomy.
AB  - PURPOSE: To compare the levels of prostaglandin E2 (PGE2) in corneal tissue after
      193-nanometer excimer laser keratectomy and mechanical keratectomy with a
      microkeratome. METHODS: Four rabbits underwent 193-nanometer excimer laser
      phototherapeutic keratectomy on one eye, and lamellar keratectomy with the
      microkeratome on the fellow eye. The corneas were harvested at 10 hours after the
      treatment and quantitated for PGE2 levels using an enzyme-linked immune assay.
      Control levels of PGE2 in untreated corneas were obtained from a previous study.
      RESULTS: Unoperated control corneas had low levels of PGE2 (1.79 +/- 1.0 pg/mL).
      Both surgical techniques resulted in a significant (p < .01) increase in PGE2.
      Corneas ablated mechanically with the microkeratome had an average PGE2 level of
      15.48 +/-5.36 pg/mL, which represented an 8.6-fold increase compared to control;
      there was an additional 330% mean increase in PGE2 concentration in the laser
      ablated corneas (51.29 +/- 36.08 pg/mL) compared to the corneas treated with
      mechanical lamellar keratectomy (p = .014). CONCLUSIONS: Mechanical and
      photochemical superficial keratectomies induce production of an inflammatory
      mediator, PGE2. The 193-nanometer excimer laser irradiation causes a greater
      increase of PGE2 production in the corneal tissue than does keratectomy with the
      microkeratome; this observation may support a role for cyclo-oxygenase inhibitors
      in postoperative therapy.

PMID- 7528610
TI  - Nonfreeze myopic keratomileusis for myopia in 158 eyes.
AB  - BACKGROUND: A prospective evaluation of non-freeze myopic keratomileusis is
      reported. METHODS: One hundred and fifty-eight eyes of 98 consecutive patients
      underwent nonfreeze myopic keratomileusis, with BKS 1000 (Eyetech-M.V.A.A.G,
      Balzers, Liechtenstein) refractive set. The preoperative myopia ranged from -6.25
      to -28.00 D. Mean follow up was 591.3 days (range, 90 to 1500 days). RESULTS: The
      logarithmic mean preoperative spectacle-corrected visual acuity was 0.48 +/- 0.31
      (20/40), and 0.44 (20/50) +/- 0.30 after 2 years and longer, whereas mean
      uncorrected visual acuity was 0.32 +/- 0.28 (20/70) in 34 of 82 (41.5%) eyes.
      After 2 years and longer, 21 of 82 (25.6%) eyes were within 1.00 D of emmetropia,
      and 43 of 82 (52.4%) were within 2.00 D. The subjective spherical equivalent
      refraction confidence interval at 90% was 9.28 D (-6.85 to +2.43 D). No
      refractive instability was detected during follow-up. We detected a trend toward
      improvement of spectacle-corrected visual acuity with time. However, after 2
      years and longer, there was an increase in astigmatism of more than 1.00 D, when
      compared to the preoperative values, and 14 of 82 (17%) eyes lost two or more
      lines of spectacle-corrected visual acuity (statistically significant: p < .01).
      CONCLUSION: The nonfreeze myopic keratomileusis procedure, with BKS 1000,
      substantially reduces moderate to high myopia, but predictability of refractive
      outcome is only fair, and the frequency of optical complications including
      irregular astigmatism is higher than desired.

PMID- 7528608
TI  - Computer aided development of antiarrhythmic agents with class IIIa properties.
AB  - Most antiarrhythmic agents were discovered accidentally. In the last decade, the
      understanding of the mechanisms of action of agents with electrophysiologic
      activity has progressed greatly. As a result, it was possible to compute, before
      the CAST trial, that the agents selected for the trial would not be effective
      against tachycardias and that the drugs would be unsafe. Extension of these
      computations to existing Class I agents indicated that they were all poor
      suppressors of ventricular tachycardia. Furthermore, a Class I agent with an
      optimal electrophysiologic profile still computes to be a two-edged sword,
      possessing both antiarrhythmic and proarrhythmic properties. Fortunately, it is
      possible to conceive of drug profiles that would be purer antiarrhythmic agents.
      For example, a drug that only upon the development of a tachycardia lengthens
      action potential duration in a use-dependent manner until the refractory period
      exceeds the tachycardia cycle length will render continuation of the tachycardia
      impossible. Recognition of chemicals that have Class IIIa properties with the
      appropriate kinetics is a challenging task. However, today's microprocessors have
      become powerful enough to characterize the Class III kinetics. A system that
      fully automatically screens for effective antiarrhythmic agents is described. It
      is expected that chemicals selected for optimal basic electrophysiologic
      properties will yield safer and more effective antiarrhythmic agents.

PMID- 7528612
TI  - Corneal sensation following excimer laser photorefractive keratectomy in humans.
AB  - BACKGROUND: For the correction of myopia, small amounts of corneal tissue-
      including corneal nerves--are removed, resulting in flattening of the central
      cornea. METHODS: We studied the changes in corneal sensation in five regions of
      the cornea following photorefractive keratectomy at varying depths. We examined
      and compared the recovery of sensation in 17 sighted myopic eyes, with
      preoperative refractive ranges from -1.00 to -7.25 D. Eyes were divided into
      shallow (0 to 30 microns) or deep (31 to 70 microns) ablation groups depending on
      the attempted laser correction. Corneal sensation was measured in the central
      ablated area and the temporal, inferior, nasal, and superior unablated regions
      preoperatively and at 1, 3, and 6 months postoperatively. RESULTS: Central and
      inferior sensation were significantly reduced in the deep ablations at 1 month
      and continued in the central cornea 6 months postoperatively. There were no
      overall differences in the sensations in the unablated nasal, temporal, and
      superior regions between either group or over time. There was a significant
      second order trend (p = .034) in these three regions, indicating a sharper
      increase in sensation from baseline in the deeper group at 1 month than the
      gradual upward trend of the shallow group. CONCLUSIONS: Corneal sensation of both
      the central ablated area and the unablated peripheral cornea is decreased after
      deep anterior stromal excimer laser ablations and does not recover within 1
      month. Although the deeper group showed isolated areas in the periphery of
      significant second order trends in sensation, the overall trends were not large,
      indicating no significant anesthetic effect. Fluctuations in sensation can be
      detected in the five regions even 6 months after excimer laser keratectomy. The
      clinical importance of these data remain to be defined.

PMID- 7528613
TI  - Topical diclofenac following excimer laser: effect on corneal sensitivity and
      wound healing in rabbits.
AB  - BACKGROUND: Diclofenac is a nonsteroidal antiinflammatory drug (NSAID) that is
      widely used systemically and topically. We studied the effect of diclofenac on
      corneal reepithelialization and corneal sensitivity after excimer laser treatment
      in rabbits. METHODS: Twelve New Zealand white rabbits were divided into four
      groups (A, B, C, and D). Groups A and B received diclofenac four times and eight
      times daily, respectively, following a central 5-millimeter epithelial
      debridement. Groups C (control) and D (diclofenac four times daily) underwent
      excimer laser ablation (30-micrometer depth) following manual debridement. Wound
      healing was compared between groups A and B and groups C and D. Sensitivity was
      recorded preoperatively and postoperatively 1 to 5 and 14 days in groups C and D
      until normal values were reestablished. RESULTS: Total time for corneal wound
      healing and epithelial migration rates was not delayed in any group receiving
      diclofenac (A, B, and D). Sensitivity after laser ablation reached a minimum of
      15% to 20% in both groups C and D by day 2 and returned to normal (100%) by day
      8. The decrease in sensitivity between group C, the controls, and group D,
      receiving diclofenac four times daily, was not statistically significant.
      CONCLUSIONS: Diclofenac can be used up to eight times daily in the rabbit without
      causing changes in corneal wound healing or epithelial migration rate. There was
      no significant, long-term reduction of sensitivity, and recovery was not affected
      by diclofenac.

PMID- 7528614
TI  - Surgical results of penetrating keratoplasty in essential iris atrophy.
AB  - BACKGROUND: Results of penetrating keratoplasty in iridocorneal endothelial
      syndrome have been considered favorable based on past studies; however,
      documented results in eyes specifically with essential iris atrophy are lacking.
      METHODS: A retrospective study was performed to evaluate all patients at the
      University of Pittsburgh with essential iris atrophy who had undergone
      penetrating keratoplasty for corneal decompensation over 21 years (1971-1992).
      RESULTS: Penetrating keratoplasty had been performed on six eyes with essential
      iris atrophy for corneal decompensation. All eyes postoperatively had evidence of
      persistent anterior uveitis resistant to corticosteroid treatment with one or
      more episodes of graft reaction. Five of the six eyes (83.3%) ultimately went on
      to graft failure. Two of the six eyes (33.3%) rejected grafts on two separate
      occasions. CONCLUSIONS: Penetrating keratoplasty in essential iris atrophy was
      frequently associated with chronic anterior uveitis and immunologic graft
      failure.

PMID- 7528615
TI  - Photoablation of gelatin with the free-electron laser between 2.7 and 6.7
      microns.
AB  - BACKGROUND: Photoablation in the infrared (IR) is an option for future refractive
      and corneal surgery; its basic principles have not yet been investigated
      systematically. For the first time, the free electron laser allows the dynamic
      study of photoablation over a wide range of wavelengths with variable
      combinations of pulselength and energy. The goal of this study is to use the free
      electron laser as a tool to describe photoablation in the IR quantitatively. We
      studied the function of wavelength as it is related to target material
      spectroscopy and the effects of corneal hydration and the pulse repetition rate.
      METHODS: Surface absorption spectroscopy of the human cornea and of gelatin as a
      proven model of the cornea was performed between 2.7 and 6.7 microns. Gelatin
      probes of well-defined thickness (140 +/- 5 microns) and controlled hydration
      (wet/dry weight 1 to 4.5) served as target material. Photoablation was performed
      with the Vanderbilt University free electron laser (Nashville, Tenn) in September
      1992 at a fluence of 1.27 J/cm2, and a macropulse of 4 microseconds, composed of
      2 ps micropulses at a 2.9 GHz pulse repetition rate. Wavelength was tunable
      between 2.7 and 6.7 microns at stable beam profiles. Ablation experiments were
      performed as a function of energy, hydration, and pulse repetition rate. Ablation
      rates were assessed by a) perforation experiments, and b) direct measurements
      using confocal laser topometry (UBM, Ettlingen, FRG). RESULTS: Ablation rate,
      assessed by perforation experiments and topometry, correlated well with the
      corresponding measured absorbencies of the target material: maximal ablation rate
      at maximal target absorption, around the 3- and 6-micrometer water absorption
      bands. The ablation threshold at 6.2 microns was 0.7 +/- 0.05 J/cm2 (perforation)
      and 0.55 +/- 0.08 J/cm2 for depth measurements. Ablation rate as a function of
      hydration increased to 2.3 (wet/dry weight) with a decrease for higher
      hydrations. Ablation rate as a function of the pulse repetition rate showed an
      increase of up to 20 Hz, where it was found to be 60% higher. CONCLUSION: The
      first systematic use of free electron laser technology positively correlated
      ablation efficiency with target material absorption, thus identifying a "new"
      promising wavelength at around 6.2 microns for materials with a high water
      content such as corneal tissue.

PMID- 7528616
TI  - Rotating brush for fast removal of corneal epithelium.
AB  - BACKGROUND: A simple new device is proposed for safe and very fast epithelial
      removal of the cornea. This is a rotating plastic brush that removes the corneal
      epithelium within a few seconds under irrigation, without causing any mechanical
      damage to the stromal surface. METHODS: Comparative SEM and TEM studies on rabbit
      corneas were carried out following epithelial removal by rotating brush and by a
      Beaver knife blade. Epithelial removal time and reepithelialization time after
      photorefractive keratectomy were evaluated in a series of 40 human sighted eyes
      treated with the brush. RESULTS: The rotating brush-abraded surface was smoother
      compared to the blade-abraded one. Additionally, the brush provoked no damage to
      the basal lamina of the rabbit corneal epithelium. In human photorefractive
      keratectomy, the mean time needed for removal of the corneal epithelium by the
      rotating brush was only 3 sec (range, 2-5 sec). Reepithelialization time
      following photorefractive keratectomy did not exceed 3 days. CONCLUSION:
      Experimental and preliminary clinical studies suggest that the new rotating
      plastic brush is a safe and fast method for removing the corneal epithelium.

PMID- 7528618
TI  - Frown incision in the cornea.

PMID- 7528619
TI  - Photorefractive keratectomy.

PMID- 7528620
TI  - Optometrists barred from using therapeutic lasers in Georgia.

PMID- 7528621
TI  - Misalignment of videokeratoscope produces pseudo-keratoconus suspect.

PMID- 7528617
TI  - Radial keratotomy and excimer laser photorefractive keratectomy for the
      correction of myopia.
AB  - PURPOSE: To compare our current knowledge of the two most common current
      refractive surgical procedures for the correction of myopia. METHODS: I reviewed
      the scientific literature and my personal experience with radial keratotomy and
      excimer laser photorefractive keratectomy to compare these two modalities.
      RESULTS: Both radial keratotomy and photorefractive keratectomy are capable of
      permanently correcting myopic refractive errors. However, each procedure has its
      individual advantages and disadvantages, with the greatest concern currently
      being the effect of wound healing on refractive outcome. The procedures are not
      mutually exclusive. CONCLUSIONS: Both radial keratotomy and photorefractive
      keratectomy will be used to surgically correct myopia for the next several years
      until newer technology is developed to improve the predictability and stability
      of refractive results currently achieved with each procedure.

PMID- 7528622
TI  - An interactive approach to GLP training.

PMID- 7528623
TI  - Building an effective training program.
AB  - Compliance with regulations usually requires documentation of training for staff
      working under the regulations. Most organizations find that the most efficient
      and cost-effective method is to conduct this training in-house using their own
      staff. Those asked to train fellow employees have the essential knowledge to
      provide, but rarely have previous experience conducting training sessions. A need
      exists to train the trainers in the techniques of effective presentations. An
      approach is presented that will aid trainers to conduct more effective programs.

PMID- 7528624
TI  - Suicide in children and adolescents in England and Wales 1960-1990.
AB  - BACKGROUND: Following reports of recent increases in adult male suicides in
      England and Wales, suicide rates for children and adolescents are reviewed.
      METHOD: By using estimated mid-year populations for five-year age bands, the
      suicide rates for 10-14 year-olds and 15-19 year-olds are calculated between 1960
      1990. The same method is used to obtain rates for 'undetermined' death and
      'accidental' death by causes comparable to suicide. RESULTS: The only group to
      show an increase in suicide rate since the 1970s has been males aged 15-19 years.
      This increase persists even when 'undetermined' and 'accidental' death rates for
      causes similar to suicide are examined. The increase is associated with an
      increase in hanging and self-poisoning with vehicle exhaust gas. CONCLUSIONS: The
      increase in suicide rate in 15-19 year-old males may indicate increased
      psychosocial stress, particularly affecting this age/gender group.

PMID- 7528625
TI  - High-dose antipsychotic medication.

PMID- 7528626
TI  - Cytomegalovirus infection in living related liver transplantation: rapid
      diagnosis by human monoclonal antibody staining of blood leucocytes.
AB  - Symptomatic cytomegalovirus (CMV) infection is a major cause of morbidity and
      mortality following orthotopic liver transplantation. Early detection and prompt
      treatment with appropriate medicine are crucial for successful outcome. As an
      early detection method, we used the CMV antigenemia test which is based on
      immunocytochemical detection of CMV immediate early antigens in blood leucocytes.
      CMV immediate early antigens were detected in blood leucocytes with direct
      immunoperoxidase technique using a horseradish peroxidase (HRP)-conjugated
      F(ab')2 fragment of human monoclonal antibody (humab C7), designated HRP-C7. Of
      the 37 living related liver transplantations we performed on pediatric patients
      between June 1990 and August 1992, we experienced four cases (10.8%) of
      symptomatic CMV infection: three CMV hepatitis and one CMV peritonitis. They were
      all treated successfully with a combination of ganciclovir and immunoglobulins.
      In ABO-incompatible cases ganciclovir was administered prophylactically. Early
      detection using this method is though to have led to these successful outcomes.
      It is concluded that HRP-C7 staining of blood leucocytes is useful for the rapid
      diagnosis of CMV infection.

PMID- 7528627
TI  - Inhibition of in vitro immunoglobulin production by a novel immunosuppressive
      drug brequinar sodium.

PMID- 7528628
TI  - Molecular cell biology and physiology of solute transport.

PMID- 7528630
TI  - RNAlign program: alignment of RNA sequences using both primary and secondary
      structures.
AB  - We have developed an algorithm and a computer program for aligning new RNA
      sequences with a bank of aligned homologous RNA sequences. Given a common folding
      structure for the bank, the program performs an alignment between the bank and a
      new sequence, optimal both in terms of primary and secondary structure. This
      method is useful to align sequences that present a common folding structure
      despite extensive divergence of their primary structures. It allows these
      preserved regions to be precisely distinguished from domains with more variable
      secondary structure. An optimal alignment of a sequence of length N with a bank
      of homologous sequences of length M is produced in O (M2N3) time and O(M2N2)
      space. For sequences that are too long for an algorithm of this complexity, a
      proposed strategy is to use a classical alignment (using only primary structure
      data) then improve it with the new algorithm in the regions where the bank stems
      are not aligned with possible stems in the new sequence. The algorithm has been
      implemented in Turbo Pascal on a PC, and has been used to align RNA sequences of
      eubacterial large ribosomal subunit.

PMID- 7528629
TI  - The cytoskeleton and membrane transport.
AB  - This review summarizes recent studies demonstrating that the actin-based
      cytoskeleton regulates the activity of many ion channels and transport proteins.
      Stretch-activated ion channels; channels conductive to chloride, to sodium, and
      to potassium; electroneutral transport proteins, including the Na(+)-K(+)-2Cl
      cotransporter, the Na+/H+ exchanger, and the organic osmolyte transporter; as
      well as water channels are all regulated by the actin cytoskeleton. Several
      potential mechanisms whereby the actin cytoskeleton and microtubules regulate
      transport protein activity are discussed.

PMID- 7528631
TI  - Nucleic acid modeling tool (NAMOT): an interactive graphic tool for modeling
      nucleic acid structures.
AB  - The helical nature of the molecule (almost all of the DNA and a significant
      portion of the RNA) makes the modeling of nucleic acids a unique task. Unlike
      other biopolymers (proteins, lipids, etc.), the integrity the structure of a
      nucleic acid molecule depends strongly on the maintenance of the base pairing
      within the molecule. Structural alterations (bending, stretching, compressing,
      etc.), in general, should not disturb the base pairings. A custom-made molecular
      modeling tool is developed taking into consideration this specific property of
      the molecule. Instead of Cartesian coordinates, the modeling is carried out on a
      set of reduced coordinates developed here in our laboratory. One of the
      advantages using this set of reduced coordinates is the readiness of maintaining
      the base pairings while altering the structure. A graphic routine is incorporated
      into the package to display the image of the molecule while the modeling work is
      being executed. The program is written in C using XView tool kit with Xlib
      routines to ensure portability to different workstations.

PMID- 7528632
TI  - Cancer statistics, 1995.
AB  - The American Cancer Society's Department of Epidemiology and Statistics reports
      its 29th annual compilation of cancer incidence, survival and mortality data for
      the United States and around the world.

PMID- 7528634
TI  - Pitfalls to avoid in the measurement of blood pressure in the elderly.
AB  - Accurate, reproducible blood pressure readings are more difficult to obtain in
      the elderly. Elderly patients have more variable blood pressure, show a reduction
      in blood pressure following meals, and can have postural hypotension,
      discrepancies in blood pressure between arms, auscultatory gaps and
      'pseudohypertension', all of which can mislead clinicians regarding these
      patients' usual blood pressure. Arrhythmias, particularly atrial fibrillation,
      make accurate blood pressure determination difficult and are more common in the
      elderly. Prostatic hypertrophy causing high pressure urinary retention is
      suggested as a common and reversible cause of hypertension in older men. Proper
      measurement of blood pressure in elderly patients demands additional thought and
      action, all of which are necessary for accurate cardiovascular risk assessment
      and proper therapeutic decisions. Increasing the number of visits and the number
      of carefully taken blood pressure readings per visit will result in a more
      accurate assessment of blood pressure in older patients.

PMID- 7528635
TI  - The Second Stanford Conference on International Standardization of Prostate
      Specific Antigen Assays.

PMID- 7528633
TI  - Purification and characterization of a protease from Pseudomonas pseudomallei.
AB  - Pseudomonas pseudomallei is the causative agent of melioidosis, a glanders-like
      disease of humans and animals. The pathogenesis of melioidosis is not well
      understood, and the role of various extracellular enzymes produced by P.
      pseudomallei in the development of this disease is not known. The present studies
      were designed to purify and characterize an extracellular protease produced by P.
      pseudomallei isolates and to test the hypothesis that this protease may play a
      role in melioidosis. The protease was present in culture supernatants as an
      enzyme with a molecular weight of 36,000 that was optimally active at 60 degrees
      C and at pH 8.0. The P. pseudomallei protease was shown to be a metalloenzyme
      requiring iron for maximal activity, and activity was inhibited in the presence
      of ethylenediaminetetraacetic acid (150 mM). Antibodies directed against an
      alkaline protease produced by Pseudomonas aeruginosa cross-reacted with the P.
      pseudomallei protease. These data indicate that the P. pseudomallei protease
      belongs to the family of alkaline proteases sensitive to metal chelators.
      Purified P. pseudomallei protease was capable of digesting a variety of
      eucaryotic protein substrates including immunoglobulins. A P. pseudomallei strain
      deficient in protease production was shown to be less virulent than the parental
      strain in an animal model of lung infection. These data suggest that this
      protease may be a significant pathogenic determinant in infections caused by P.
      pseudomallei.

PMID- 7528636
TI  - The significance of nucleolar organizer region (AgNOR) score in predicting
      meningioma recurrence.

PMID- 7528637
TI  - Reactivity to B cell epitopes within hepatitis C virus core protein and
      hepatocellular carcinoma.
AB  - Our aim was to investigate the existence of an association between B cell
      responsiveness to hepatitis C virus (HCV) core protein and progression of liver
      disease. In fact, the persistence of HCV infection is permitted by avoidance of
      viral clearance, despite chronic inflammation in the liver; this process ends
      with the development of hepatocellular carcinoma in many patients. On the basis
      of computerized prediction of antigenicity of the genomic sequence of HCV core
      protein, three 15-mer peptides (named Q15V, R15P, and G15V) were synthesized to
      be used as antigens in an enzyme immunoassay. Sera from 97 patients (65 males and
      32 females) were tested: 43 patients had mild chronic liver disease
      (steatofibrosis, chronic persistent, or chronic active hepatitis) and 54 had
      cirrhosis, which was complicated by hepatocellular carcinoma (HCC) in 19. Seventy
      six patients were positive to anti-HCV testing by second generation ELISA and 21
      were negative. Rates of positivity for synthetic peptides in anti-HCV-positive
      versus anti-HCV negative patients were as follows: 53 of 76 and 0 of 21 for anti
      Q15V; 41 of 76 and 0 of 21 for R15P; and 67 of 76 and 2 of 21 for G15V. Rates of
      positivity to anti-Q15V and anti-G15V were similar among diagnostic groups
      (Pearson's chi 2, 1.97, P > 0.10 and 0.45, P > 0.10), whereas anti-R15P
      antibodies were detected at a significantly lower rate in patients with HCC
      (2/13) in comparison to mild chronic liver disease (22/35) and cirrhosis (17/28)
      (Pearson's chi 2, 9.42, P < 0.01). We conclude that anti-R15P antibodies are
      uncommon in anti-HCV-positive patients with HCC. During the course of chronic HCV
      infection, anti-R15P testing might help to identify a subgroup at higher risk to
      develop HCC.

PMID- 7528638
TI  - Identification of Meth A sarcoma-derived class I major histocompatibility complex
      associated peptides recognized by a specific CD8+ cytotoxic T lymphocyte.
AB  - The finding that class I major histocompatibility complex (MHC)-restricted
      cytotoxic T lymphocytes (CTL) recognize peptide antigens (epitopes) bound to
      class I MHC molecules has accelerated efforts to identify CTL-defined tumor
      peptides for the development of peptide-based cancer immunotherapy. The Meth A
      sarcoma is probably one of the best studied of all murine tumors. It is extremely
      lethal unless protective immunity is induced. We recently reported the
      characterization of a cloned H-2Kd-restricted, CD8+ anti-Meth A CTL line (CTLMA
      9C; Frassanito et al., Cancer Res., 54: 4424-4429, 1994). The cytotoxic
      reactivity of this CTL was shown to be restricted to Meth A sarcoma, and the
      results of the analysis of the immunogenicity of the CTL-resistant variant of
      Meth A, designated Meth A4R, indicate that the CTL-defined epitope is functional
      in tumor rejection. Here we have isolated class I MHC-associated peptides from
      Meth A sarcoma by mild acid treatment and resolved them into sixty fractions by
      reverse phase-HPLC. These fractions were then tested for their ability to
      sensitize the DBA/2 mastocytoma P815 to cytolysis by the anti-Meth A CTL. A
      single fraction, fraction 27, has been repeatedly identified as containing the
      CTL-defined epitope. Peptides eluted from the CTL-resistant variant, Meth A4R,
      failed to sensitize P815 to cytolysis by the anti-Meth A CTL, while fraction 27
      derived from Meth A sensitized Meth A4R to lysis by the CTL. These findings
      confirm the peptide nature of the epitope recognized by CTL on the surface of
      Meth A. Our future efforts will focus on the identification and sequence analysis
      of the tumor peptides and the development of a tumor peptide-based vaccine model
      for immunotherapy.

PMID- 7528639
TI  - Structural studies of the Escherichia coli O90 O-antigen polysaccharide.
AB  - The O-specific side-chain of the lipopolysaccharide from Escherichia coli O90 has
      been investigated using methylation analysis, partial hydrolysis, and NMR
      spectroscopy as the principal methods. It is concluded that the polysaccharide is
      composed of tetrasaccharide repeating-units having the following structure.
      [formula: see text] The polysaccharide contains approximately one mole of O
      acetyl groups per repeating unit, located on the fucose residue.

PMID- 7528640
TI  - Structural comparison of the O6 specific polysaccharides from E. coli O6:K2:H1,
      E. coli O6:K13:H1, and E. coli O6:K54:H10.
AB  - Two distinct forms of the O6 antigen (LPS) from E. coli were analysed using 1H
      and 13C NMR spectroscopy. Their structures were found to be [formula: see text]
      In the O6-specific polysaccharide from E. coli O6:K2 and O6:K13, X is beta-D-Glc
      p, as had previously been shown for the O6 polysaccharide from E. coli O6:K15; in
      the O6 specific polysaccharide from E. coli O6:K54, X is beta-D-Glc pNAc.

PMID- 7528641
TI  - The structure of the Citrobacter freundii O8a,8b O-specific polysaccharide
      containing D-xylofuranose.

PMID- 7528642
TI  - Structure of the O16 polysaccharide from Escherichia coli O16:K1: an NMR
      investigation.
AB  - The polysaccharide moiety of the O16 antigen (lipopolysaccharide) consists of D
      glucopyranose, D-galactofuranose, L-rhamnopyranose, and 2-acetamido-2-deoxy-D
      glucopyranose in the molar ratios 1:1:1:1. It is O-acetylated with one acetyl
      group per repeating unit. One- and two-dimensional NMR spectroscopy of the
      polysaccharide before and after O-deacetylation showed that the O16
      polysaccharide has the structure [formula: see text]

PMID- 7528643
TI  - The structure of the O-specific polysaccharide of the lipopolysaccharide from
      Chromobacterium violaceum NCTC 9694.

PMID- 7528644
TI  - [MBP P89-101 induced experimental allergic encephalomyelitis in mice and
      establishment of CD4+ T cell line specific to MBP P89-101].
AB  - SJL/J mice were immunized with peptide 89-101 of myelin basic protein in FCA and
      developed EAE around 13th day after immunization. Lymph-nodes were collected at
      the time of onset and lymphocytes were prepared and cultured with MBP P89-101 in
      vitro for 3 weeks. X-ray irradiated (3000R) syngeneic spleen cells were added as
      antigen presenting cells. Antigen stimulated blast cells were isolated with
      Ficoll-Hypaque. MBP P89-101 specificity of cells were measured by 3H-TdR
      incorporation. MBP P89-101 activated cells were stained with PE-CD4 and analyzed
      by FACS. The results showed that all of the blast cells were of CD4 positive
      phenotype, specific to MBP P89-101.

PMID- 7528645
TI  - [Evaluation of the clinical acute electrophysiological effects of propafenone
      using transesophageal atrial pacing].
AB  - The clinical acute electrophysiological effects of propafenone were evaluated
      using transesophageal atrial pacing (TEAP) in 65 patients with various
      arrhythmias. The mean age of the patients was 41 years. Incremental pacing and
      programmed ectopic stimulation were performed on each patient before and during
      drug administration. Propafenone was given as a bolus injection of 1.5mg.kg-1
      body weight followed by drip infusion at a rate of 1 mg.min-1. S-R, P wave, P-R
      and QRS intervals were prolonged from 194.43 +/- 21.59, 97.49 +/- 10.92, 148.00
      +/- 16.20 and 82.21 +/- 7.18ms 223.00 +/- 29.25, 100.22 +/- 10.60, 166.60 +/-
      20.10 and 86.54 +/- 7.19ms, respectively (P < 0.005), A-V conduction system
      effective refractory period (AVCSERP) was prolonged from 316.35 +/- 82.97ms to
      360.31 +/- 82.67ms (P < 0.0001) in the treated group. There was no change of
      atrial ERP and QTc interval (P > 0.05). Fast and slow pathway ERP was prolonged
      by 13% and 28% of the control value, respectively (P < 0.015), and accessory
      pathway ERP was prolonged from 278.89 +/- 27.13ms to 305.56 +/- 33.58ms (P <
      0.001), in the treated group. Sinus cycle length, corrected sinus nodal recovery
      time and total sinus-atrial conductive time were significantly prolonged (P <
      0.0001). The results can partially explain the antiarrhythmic effects and the
      side effects of propafenone. TEAP is dependable in evaluating the clinical
      electrophysiological effects of drugs.

PMID- 7528646
TI  - Symptomatic, stage IV, non-small-cell lung cancer (NSCLC): response, toxicity,
      performance status change and symptom relief in patients treated with cisplatin,
      vinblastine and mitomycin-C.
AB  - In a series of 46 symptomatic patients with metastatic, stage IV, non-small-cell
      lung cancer (NSCLC), we used a three-drug combination with cisplatin (120 mg/m2),
      vinblastine (6 mg/m2) and mitomycin-C (6 mg/m2) (PVM), repeated every 3 weeks.
      After two courses, we observed that none of the patients had achieved a complete
      response; 33% (15/46) had partial response (95% confidence limits: 19.2-46.8);
      39% (18/46), stable disease and 28% (13/46), progressive disease. Median response
      duration was 14.0 weeks (range, 4-36.7), median time to progression 22.4 weeks
      (range, 7-44.4), and median survival time 26.4 weeks (range, 1-103). WHO grade
      III-IV myelotoxicity occurred in 15.2% of the courses administered, affecting
      39.5% of patients, and severe nephrotoxicity was observed in 9.3% of patients. No
      toxic death occurred. The post-treatment KPS score increased in 7 patients with
      partial response (47%), 4 with stable disease (22%) and 1 with progressive
      disease (8%), while it decreased in 3 patients with partial response (20%), 3
      with stable disease (17%) and 10 with progressive disease (77%). In all, KPS
      increased in 12/46 cases (26%). However, no statistically significant difference
      was observed when the KPS score before and after treatment was compared in the
      total group of patients or when it was compared in the total group of patients or
      when it was compared in responders and in non-responders. After chemotherapy,
      there was complete disappearance of at least one symptom in 27.1% of cases and
      improvement in 27.1%. Overall, major symptom control occurred in 54.3% of cases,
      with a median palliation time lasting 10 weeks (range, 4-32). Patients with
      partial remission and stable disease achieved symptomatic palliation in 90% and
      55.5% of cases, respectively. When we compared the palliation rate between
      responders and non-responders, a significant difference was noted (Chi-square
      test: P < 0.05). Although our schedule did not produce a higher objective
      response rate and the KPS score was not significantly improved, the symptom
      palliation appeared worthwhile considering the highly unfavourable prognosis of
      the patients investigated.

PMID- 7528648
TI  - Lack of evidence for linkage of the endothelial cell nitric oxide synthase gene
      to essential hypertension.
AB  - BACKGROUND: The basal release of nitric oxide by the endothelium plays an
      important role in regulating blood flow and pressure and mediates most of the
      endothelium-dependent vasodilation. Impairment of nitric oxide production by
      specific inhibitors increases blood pressure in humans, and several reports
      suggest that hypertensive subjects have a blunted endothelium-dependent
      vasodilatation that might be secondary to decreased nitric oxide production from
      the vessel wall. METHODS AND RESULTS: To determine whether the endothelial nitric
      oxide synthase gene is involved in human essential hypertension, we identified
      informative biallelic and multiallelic markers of this locus and performed case
      control and linkage studies in hypertensive subjects and normotensive control
      subjects. We used the affected sib pair method to test for potential linkage in
      145 hypertensive pedigrees (269 sib pairs, 346 subjects) with a highly
      polymorphic marker of the nitric oxide synthase gene (polymorphism information
      content of 92%). There was no evidence for linkage among affected siblings. The
      95% upper confidence limit of this value suggests that at most 1% of alleles in
      excess of expected are shared. We also identified two informative biallelic
      markers of this gene to perform a case-control study on white hypertensive and
      normotensive subjects. Similar genotype distributions between the two groups were
      noted for both markers. Estimated haplotype frequencies by maximum likelihood
      methods combining the two biallelic markers were also similar in both groups.
      CONCLUSIONS: These findings do not suggest that common molecular variants of the
      endothelial nitric oxide synthase gene are involved in essential hypertension.

PMID- 7528649
TI  - Increase and redistribution of cardiac mast cells in auricular thrombosis.
      Possible role of kit ligand.
AB  - BACKGROUND: The atrial appendage is a predilection site for thrombus formation.
      Mast cells (MC) are a rich source of mediators that may be involved in the
      regulation of thrombus formation. We examined number, distribution, and phenotype
      of MC in thrombosed versus unaffected auricles to elucidate their possible role
      in auricular thrombosis (AUTHR). METHODS AND RESULTS: Sections of atrial
      appendages (AUTHR, n = 14; controls (CO), n = 13) were analyzed for MC by Giemsa,
      toluidine blue, and berberine sulfate stains and by immunohistochemistry. Cardiac
      MC expressed CD antigens corresponding to the classic MC phenotype as well as
      tryptase, chymase, and heparin. Thrombosis was associated with a twofold increase
      in the number of MC in the total appendage (CO, 3.1 +/- 1.0 versus AUTHR, 6.4 +/-
      1.1 MC/mm2, P < .01). Moreover, in AUTHR, a redistribution of MC to the upper
      endocardium was observed (AUTHR, 5.3 +/- 1.4 versus CO, 0.07 +/- 0.15 MC/mm2, P <
      .01). Mast cell growth factor (MGF) was expressed in the endothelium and
      subendothelial space of thrombosed appendages but not in the normal endocardium.
      Overexpression of MGF was accompanied by a weak or absent expression of the MGF
      receptor c-kit on redistributed MC in AUTHR. Patients with unilateral atrial
      appendage thrombosis did not exhibit a MC increase or redistribution in the
      unaffected contralateral appendage. No augmentation of other inflammatory cells
      was observed. Stimulation of isolated cardiac MC with MGF resulted in mediator
      release. CONCLUSIONS: This study provides evidence that AUTHR is associated with
      MC increase and redistribution and MGF overexpression. The role of redistributed
      MC and their mediators in the pathophysiology of atrial thrombosis requires
      further investigation.

PMID- 7528650
TI  - Predicting recovery from aphasia with connectionist networks: preliminary
      comparisons with multiple regression.
AB  - We trained a series of simulated neural networks with the raw scores on the
      Western Aphasia Battery from 91 aphasic patients. Patients were tested at 3 and
      at 12 months post onset. The most successful network we trained is able to
      predict AQ for an individual in 12 months from the raw scores at 3 months post
      onset to a tolerance of + or -4.5. We then compared the relative success of a
      small range of trained networks to predict recovery with linear multiple
      regression. With the small groups of subjects involved in this preliminary study,
      the networks appeared to be more successful at predicting recovery.

PMID- 7528647
TI  - Tetrahydrobiopterin and dysfunction of endothelial nitric oxide synthase in
      coronary arteries.
AB  - BACKGROUND: The L-arginine/nitric oxide pathway plays a key role in the
      regulation of arterial tone. Biosynthesis of nitric oxide requires activation of
      nitric oxide synthase in the presence of tetrahydrobiopterin as a cofactor.
      Biochemical studies demonstrated that activation of purified nitric oxide
      synthase at suboptimal concentrations of tetrahydrobiopterin leads to production
      of hydrogen peroxide. The present experiments were designed to determine whether
      in coronary arteries inhibition of tetrahydrobiopterin synthesis may favor nitric
      oxide synthase-catalyzed production of hydrogen peroxide. METHODS AND RESULTS:
      Primary branches of canine left anterior descending artery were incubated for 6
      hours in minimum essential medium in the presence or in the absence of the
      tetrahydrobiopterin synthesis inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP;
      10(-2) mol/L). Arterial rings were suspended for isometric tension recording.
      Production of cGMP was measured by radioimmunoassay. Experiments were performed
      in the presence of indomethacin (10(-5) mol/L). During contractions to the
      thromboxane A2/prostaglandin H2 receptor agonist U46619 (10(-7) mol/L), calcium
      ionophore A23187 (10(-9) to 10(-6) mol/L) caused endothelium-dependent
      relaxations. A nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester
      (3 x 10(-4) mol/L), significantly inhibited these relaxations. In DAHP-treated
      arteries, relaxations to A23187 and its stimulating effect on cGMP production
      were significantly reduced in the presence of catalase (1200 U/mL). By contrast,
      catalase did not exert any effect in rings incubated in the absence of DAHP.
      Furthermore, the inhibitory effect of catalase on A23187-induced relaxations was
      abolished when coronary arteries were incubated in the presence of DAHP plus a
      liposoluble analogue of tetrahydrobiopterin, 6-methyltetrahydropterin (10(-4)
      mol/L). CONCLUSIONS: The present study suggests that hydrogen peroxide may be a
      mediator of endothelium-dependent relaxations in coronary arteries depleted of
      tetrahydrobiopterin. This initially compensatory response, triggered by a
      dysfunctional nitric oxide synthase, may represent an important mechanism
      underlying oxidative vascular injury.

PMID- 7528653
TI  - [Surgical widening of strictures in the small intestine in Crohn disease].
AB  - Twenty-two stricture plasties were performed in five patients with multiple
      stenosis of the small intestine due to Crohn's disease. Immediate post-operative
      results were satisfactory but progressive degradation followed. These findings
      are similar to those reported in the literature on this technique which does not
      give better results than other methods since none have an effect on the clinical
      course of the disease. The only advantage is to decrease the amount of intestinal
      mutilation.

PMID- 7528651
TI  - Differential distribution of the HNK-1 carbohydrate epitope in the vertebrate
      retina.
AB  - The expression of the cell adhesion-related HNK-1 carbohydrate epitope in the
      retina and ciliary body was studied in different vertebrates and in man. A series
      of eyes from 4 fish, 5 bird, and 9 mammalian species was analyzed by
      immunohistochemistry with monoclonal antibodies (MAb) HNK-1 and VC1.1 to the HNK
      1 epitope, and with MAb SY38 to synaptophysin. Additionally, 7 morphologically
      normal human eyes were studied. In all fishes, as well as in baboons and man, the
      radial glia and all retinal layers except the photoreceptor cell layer were
      immunoreactive for the HNK-1 epitope. In all birds, the nerve fiber layer and
      both plexiform layers were labelled. In nonprimate mammals only the plexiform
      layers were immunoreactive. Fine differences in this general immunoreaction
      pattern were seen in different species. Mab SY38 labeled both plexiform layers of
      mammals only. In the ciliary body, immunoreaction for the HNK-1 epitope was seen
      in the inner connective tissue layer only in man, but the ciliary nerves were
      labelled in all species except the mouse and rat. The HNK-1 epitope seems to be
      phylogenetically conserved in the retina, where the HNK-1 immunoreactive
      plexiform layers possibly are overlapped with HNK-1 reactive radial glial cells
      in fishes and primates. Instead in the inner connective tissue layer of the
      ciliary body, the HNK-1 epitope is not phylogenetically conserved.

PMID- 7528652
TI  - Malignancies of the biliary tree.

PMID- 7528654
TI  - [Cultivation and ultrastructural investigation of human iris pigment epithelial
      cells].
AB  - The iris pigment epithelial cells of 10 human eyes were cultivated in vitro.
      RESULTS: The iris pigment epithelial cells obtained directly by scraping were
      easier to grow and to be passaged than those obtained by enzyme digestion. Under
      the inverted light microscope, primary cells appeared multigonal and arranged in
      monolayer, there were abundant pigment granules in the cytoplasm, and the nuclei
      each of which contained 1 or 2 nuclei were relatively transparent. Pigment
      granules diminished in succeeding generations. Under the transmission electron
      microscope, pigment granules were rich in the cytoplasm and there were plenty of
      microvilli at the cell membrane. There were maculae occludentes and desmosomes
      present in the intercellular space. The cultivated cells showed positive reaction
      of keratin antigen in an immunohistochemical assay. The characteristics mentioned
      above are consistent with the criteria of iris pigment epithelial cells.

PMID- 7528656
TI  - [Clinical analysis of 126 cases with NHL in extra-node of head and neck patients
      in stage I and II].
AB  - From 1987.1.1. to 1990. 12. 31. 126 cases of extranode untreated non-Hodgkin's
      lymphoma (NHL) in I-II stage were analysed. All of the 126 cases had proved by
      pathology. The sites of primary disease were oral-pharynx in 64.3%, nasal cavity
      in 31% and others in 4.7%. The age of patients was between 5-69 (30-60 in 62.7%).
      According to the international working dassification, there was 1 case of low
      grade, 48 (38%) of intermediate and 77(61%) of high grade. According to Ann Arbor
      clinical staging, there were 33 cases of stage I and 93 cases of stage II.
      According to the pathological grades and clinical stages, the treatment was
      divided into 4 groups. (1) CT-RT 63 cases, (2) RT-CT 26 cases, (3) RT 32 cases
      and (4) CT 5 cases. After treatment, CR were obtained in 101 cases, PR 18 cases
      and P 3 cases, CR+PR were 97.5%. The 1,2,3,4,5 years survival rates of the 126
      cases were 83.3% (105/126), 70.6% (89/126), 68.2% (60/88), 62.2% (46/74), 58.3%
      (21/36), respectively. CONCLUSION: (1) The pathological grades were not closely
      related to the survival rate of patients. (2) The comparison of clinical stages
      I:II showed a P value < 0.05. (3) The comparison of survival rates of CR:PR:P
      showed a P value < 0.05 and < 0.001, respectively. (4) There was no statistically
      significant difference in the four treatment protocols. But the multitherapy
      group was better. (5) Before the RT, four cycles of CT showed a better result
      than that of 1-3 cycles.

PMID- 7528655
TI  - [Effect of recombinant human stem cell factor (rhSCF) on self-renewal of
      stem/progenitor cells of human acute myelogenous leukemia].
AB  - Using serum-free culture system and liquid/semi-solid dual culture technique, we
      examined the effect of rhSCF on self-renewal of the stem/progenitor cells of
      human acute myelogenous leukemia (AML-CFU). The results revealed that the rhSCF
      as a hematopoietic growth factor (HGF) exerted its effect hierarchically earlier
      than interleukin-3 and granulocyte/macrophage colony-stimulating factor on AML
      CFU. rhSCF, whether used alone or in combination with other HGFs, showed
      potential maintenance of self-renewal of AML-CFU in most AML patients studied.
      However, considerable discrepancy existed in maintenance among various FAB types
      of patients or even in patients with the same FAB type. It is suggested that SCF
      may play an important role in the pathological development of AML.

PMID- 7528658
TI  - Inhibition of NO synthase increases the severity of kainic acid-induced seizures
      in rodents.
AB  - The nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (NNA) and the
      putative brain-selective NO synthase inhibitor 7-nitroindazole (7-NI) were used
      to determine the role of endogenous NO on seizures induced by kainic acid (KA) in
      rats and KA, pilocarpine, bicuculline, picrotoxin and pentylenetetrazole (PTZ) in
      mice. Rats given a subconvulsant dose of KA (6 mg/kg, i.p.) had seizures after
      they had been pretreated with NNA (50 mg/kg, i.p.). With a higher dose of KA (12
      mg/kg, i.p.), NNA caused an increase in wild running seizures and mortality.
      Unlike NNA, 7-NI had no effect on KA-induced seizures. Similarly, NNA but not 7
      NI caused a worsening of seizures in mice measured as a shortening of seizure
      latency and an increase in wild running and mortality. The effect of NNA on
      seizure latency was completely reversed by the competitive substrate for NO
      synthase, L-arginine. NNA had no effect on seizure latency following any of the
      other convulsants and increased mortality following pilocarpine and picrotoxin
      alone. Our results indicate that NNA may enhance the severity of KA-induced
      seizures through suppression of NO synthase activity in the vascular endothelium.
      The resulting impairment of cerebrovascular autoregulation may cause a mismatch
      between metabolic demand and blood flow during seizures leading to facilitation
      of spread. The absence of a comparable effect of NNA on other seizure models may
      indicate differences in the degree to which seizure activity in different models
      is influenced by the metabolic impairment secondary to decreased blood flow.

PMID- 7528659
TI  - A critical overview on the role of the Nd:YAG laser in the treatment of benign
      prostatic hypertrophy.

PMID- 7528657
TI  - Evidence for a K+ channel in bovine chromaffin granule membranes: single-channel
      properties and possible bioenergetic significance.
AB  - A K+ channel was incorporated into voltage-clamped planar lipid bilayers from
      bovine chromaffin granules and resealed granule membranes ("ghosts"). It was not
      incorporated from plasma membrane-rich fractions from the adrenal medulla. The
      channel had a conductance of approximately 400 pS in symmetric 450 mM KCl, with
      the permeability sequence K+ > Rb+ > Cs+ > Na+ > Li+, and was insensitive to both
      Ca2+ and charybdotoxin. It exhibited complex gating kinetics, consistent with the
      presence of multiple open and closed states, and its gating was voltage
      dependent. The channels appeared to incorporate into bilayers with the same
      orientation, and were blocked from one side (the side of vesicle addition) by 0.2
      1 mM TEA+. The block was slightly voltage-dependent. Acidification of resealed
      granule membranes in response to external ATP (which activated the vacuolar-type
      ATPase) was significantly reduced in the presence of 1 mM intralumenal TEACl
      (with 9 mM KCl), and parallel measurements with the potential-sensitive dye
      Oxonol V showed that such vesicles tended to develop higher internal-positive
      membrane potentials than control vesicles containing only 10 mM KCl. 1 mM TEA+
      had no effect on proton-pumping activity when applied externally, and did not
      directly affect either the proton-pumping or ATP hydrolytic activity of the
      partially-purified ATPase. These results suggest that chromaffin granule
      membranes contain a TEA(+)-sensitive K+ channel which may have a role in
      regulating the vesicle membrane potential.

PMID- 7528660
TI  - Predictive value of pathological features for progression after radical
      prostatectomy.
AB  - OBJECTIVE: 10-30% of patients with T1/T2 prostate cancer submitted to radical
      prostatectomy ultimately fail. It may be important to detect failure as early as
      possible in order to evaluate the extent of recurrent/residual disease and
      initiate adjuvant therapy. SUBJECTS AND METHODS: 100 consecutive patients with
      localized prostate cancer treated by radical prostatectomy have been monitored
      using the hypersensitive Pros-check prostate-specific antigen (PSA) assay
      (detection level 0.1 ng/ml). The predictive value of positive surgical margins,
      involvement of seminal vesicles and perineural spaces as well as Gleason's score
      for biological failure (persistent or recurrent detectable PSA) has been
      retrospectively evaluated. RESULTS: Overall 40% of the patients had biological
      failure (defined as persistence of a detectable or rising PSA after
      undetectability) and 38% had positive surgical margins. The three main predictive
      criteria of biological failure were capsular perforation, involvement of seminal
      vesicles and/or positive margins. All patients in whom these criteria were
      positive progressed. Seminal vesicle invasion was associated with biological
      failure in 95% of the cases. 66.7% of the patients with extracapsular disease but
      no seminal vesicle invasion progressed. 15% of pT2 patients experienced a
      persistent/recurrent postoperative PSA and were upstaged to pT3 after
      reevaluation of the specimen. CONCLUSION: Efforts should be made to increase the
      preoperative evaluation of seminal vesicle and pericapsular status by a more
      sophisticated technique of prostate biopsy in order to avoid noncurative surgery.

PMID- 7528661
TI  - Prediction of lymphatic spreading in prostatic cancer by prostate-specific
      antigen and Gleason's score.
AB  - A total of 58 patients have undergone bilateral pelvic lymphadenectomy as a
      staging procedure for clinically localized adenocarcinoma of the prostate. Of
      these, 19 patients (33%) had pelvic lymph node involvement. When a cutoff value
      of 50 ng/ml was used, the preoperative prostate-specific antigen (PSA) value had
      a positive predictive value of 57% for pelvic lymph node metastasis. Of the
      patients with PSA < 20 ng/ml, only 1 (4%) had evidence of lymph node metastasis.
      None of the patients with well-differentiated tumor (Gleason 2-4) had lymphatic
      spreading. In contrast, 82% of patients with poorly differentiated tumor (Gleason
      8-10) had positive pelvic lymph nodes. Those patients with high PSA (> or = 20
      ng/ml) and high Gleason's score (> or = 8) had the highest incidence of nodal
      extension (90%).

PMID- 7528662
TI  - Safety, side effects and patient acceptance of the antiandrogen Casodex in the
      treatment of benign prostatic hyperplasia.
AB  - Casodex, a new nonsteroidal antiandrogen, was investigated in this double-blind,
      randomized, placebo-controlled study comprising 28 evaluable patients with benign
      prostatic hyperplasia, who received Casodex at a dosage of 50 mg daily or a
      placebo for 24 weeks. The good safety profile of Casodex was confirmed. In common
      with other nonsteroidal antiandrogens, Casodex was associated with breast
      enlargement and/or tenderness, being reported by all patients upon direct
      questioning. A change in sexual function was assessed by two questionnaires, one
      of them revealing no statistically significant difference between the groups.
      However, using an alternative questionnaire, approximately half of the patients
      reported reduced erectile function (p = 0.002), mostly partial, and reduced
      sexual activity (p = 0.015), whereas libido was well maintained when compared to
      the placebo. Casodex was not associated with hot flushes. No other side effects
      of clinical significance were seen, and Casodex was well tolerated by the
      majority of the patients.

PMID- 7528663
TI  - Use of a 7-day diary for urinary symptom recording.
AB  - A cohort of 254 men, aged 40-79 years, was followed up at 1 year in a community
      based survey of benign prostatic hyperplasia. Immediately after completing a
      questionnaire about the occurrence of 12 urinary symptoms over the previous
      month, the men were invited to keep a prospective diary asking about the same
      symptoms over 7 consecutive days in order to assess the amount of day-to-day
      variation in symptoms and to examine to what extent the findings reflected those
      of the retrospective questionnaire. The majority of men reported minor degrees of
      daily fluctuations in symptoms. Only modest correlations existed between the
      diary mean and maximum score for each symptom and the corresponding retrospective
      questionnaire score. Where repeated assessments of urinary symptom status are
      considered necessary a prospective diary may be more appropriate than a
      retrospective questionnaire.

PMID- 7528665
TI  - Only simultaneous blocking of the L- and P-selectin completely inhibits
      neutrophil migration into mouse peritoneum.
AB  - We have examined the inhibitory effect of monoclonal antibodies against mouse P-,
      E- and L-selectin on the migration of neutrophils into the chemically inflamed
      peritoneum of the mouse. For this purpose; monoclonal antibodies were raised
      against mouse P- and E-selectin, which block cell adhesion. We found that
      blocking of each selectin alone inhibited neutrophil migration to a similar
      degree ranging from 63% to 72%. Of the three possible combinations of antibodies
      against two different selectins only the combination of anti-P- and anti-L
      selectin antibodies caused an essentially complete blockade of neutrophil
      emigration. Only the effects of these two antibodies were additive, while the
      effect of anti-E-selectin antibodies did not add to the effect of antibodies
      against P- or L-selectin. Thus, although E-selectin is involved in neutrophil
      migration into the inflamed peritoneum of the mouse, it cannot compensate the
      block of the other two selectins which seem to play the dominant role in this
      process.

PMID- 7528664
TI  - CD9 antigen is an accessory subunit of the VLA integrin complexes.
AB  - The CD9 antigen is a cell surface glycoprotein of unknown function which belongs
      to the tetraspans family. We demonstrate here, by precipitation, Western blotting
      and co-capping experiments, that this molecule is associated with a large
      fraction of beta 1 integrins in two cell lines, the pre-B cell line NALM-6 and
      the megakaryocytic cell line HEL. In HEL cells, CD9 antigen is only associated
      with VLA-4. In contrast, in NALM-6 cells, CD9 antigen is associated with both VLA
      4 and VLA-5. On the other hand, only the beta 1 chain is co-precipitated with the
      CD9 antigen in transfected L cells. These data show that the CD9 antigen is
      associated with the beta 1 chain rather than with a particular integrin. CD9
      monoclonal antibodies (mAb) did not modify the binding of HEL and NALM-6 cells to
      fibronectin, laminin or collagen. The association of CD9 antigen to VLA integrins
      is strengthened by the fact that both CD9 and anti-VLA mAb induce aggregation of
      the two cell lines and inhibit their migration in Transwell chambers. Because the
      aggregating effect, but not the inhibition of migration, is observed in CEM or
      CD9-transfected CEM cells, these two effects are likely to be mediated by
      different mechanisms.

PMID- 7528666
TI  - B7/BB-1 antigen expression on adult human microglia studied in vitro and in situ.
AB  - In this study, we have examined the expression and function of B7/BB-1 on
      individual glial cells, by utilizing surgically resected adult human central
      nervous system (CNS) tissues, tissues derived from fetal human CNS, and pathology
      material from cases of multiple sclerosis (MS). Immunofluorescence analysis using
      enriched adult human derived cultures of microglia and oligodendrocytes, and
      mixed microglia/astrocyte cultures, demonstrated that B7/BB-1 was expressed on
      microglia. Adult human-derived oligodendrocytes and astrocytes, and human fetal
      astrocytes were B7/BB-1 negative under all culture conditions. Flow cytometry
      studies demonstrated a low basal level of B7/BB-1 expression on microglia that
      was up-regulated following incubation with interferon-gamma (IFN-gamma). Co
      culture of purified fresh allogeneic CD4+ T cells with microglia for 24 h
      resulted in clustering of T cells around microglia and microglial B7/BB-1
      expression. Preincubation of microglia with an anti BB-1 monoclonal antibody
      (mAb) prior to microglia: CD4+ T cell co-cultures resulted in partial inhibition
      of the ability of microglia both to present recall antigen to autologous CD4+ T
      cells and to present antigen to allogeneic CD4+ T cells in primary mixed
      lymphocyte reaction (1 degree MLR). The CTLA-4 Ig fusion protein inhibited the
      ability of microglia to present antigen in both antigen presentation assays to an
      even greater extent than did the anti BB-1 mAb. The BB-1 antibody also inhibited
      the ability of microglia to stimulate previously activated T cells in a secondary
      2 degrees MLR. In sections of multiple sclerosis brain, B7/BB-1 expression was
      observed on activated microglia in select parenchymal lesions, and on
      perivascular cells and infiltrating monocytes. B7/BB-1 immunoreactivity was not
      found in normal appearing white matter from MS brain or from non-inflammatory
      brain specimens. Our results indicate that the B7/BB-1 molecule plays a
      functional role in the capacity of microglia to serve as CNS antigen-presenting
      cells that can both initiate and perpetuate CD4+ T cell activation.

PMID- 7528667
TI  - Structure of the human APO-1 gene.
AB  - APO-1/Fas (CD95) is a type 1 transmembrane protein that belongs to the tumor
      necrosis factor/nerve growth factor receptor family characterized by cysteine
      rich extracellular domains. Cross-linking of APO-1 mediates apoptosis in a
      variety of cells. In the present study we report the isolation and
      characterization of the human APO-1 gene spanning approximately 25 kb of human
      chromosome 10. The gene consists of nine exons (25 bp to > 1.44 kb) separated by
      eight introns (152 bp to approximately 12 kb). The boundaries of exon 2 to 5
      encoding the extracellular region do not match the boundaries of the three APO-1
      protein subdomains. Exon structure and functional protein domains correspond for
      exon 6 encoding the transmembrane region and for exon 9 encoding the "death
      domain". By a polymerase chain reaction-based approach we localized major
      transcriptional start sites in human spleen cells 77 and 73 nucleotides upstream
      of the translation initiation codon of the human APO-1 gene. Minor initiation
      sites were found at positions -128, -111, -91, and -74. The 5' flanking sequence
      of the human APO-1 gene is GC rich, contains a high number of CpG dinucleotides
      and lacks a consensus TATA box. Consensus binding sites for the transcription
      factors Sp1, AP-1, AP-2, GAF, NF-kappa B, and NF-AT were found. The elucidation
      of the human APO-1 gene structure will facilitate the study of its involvement in
      various diseases such as in autoimmunity.

PMID- 7528668
TI  - Interleukin-2 induces tyrosine phosphorylation and nuclear translocation of stat3
      in human T lymphocytes.
AB  - An early biochemical event associated with T cell activation through the
      interleukin-2 receptor (IL-2R) is tyrosine phosphorylation of several
      intracellular substrates. The exact mechanism by which IL-2 regulates
      transcription of different genes is presently unknown. Here, we report that
      stimulation through the IL-2R induced tyrosine phosphorylation and subsequent
      nuclear translocation of stat3, a newly identified member of the signal
      transducers and activators of transcription (STAT) family of proteins. In
      contrast, stat1 proteins were not tyrosine phosphorylated after IL-2 ligation,
      whereas tyrosine-phosphorylated stat1 proteins (91 and 84 kDa proteins) were
      translocated to the nucleus following interferon-gamma treatment of HeLa cells.
      Apart from stat3, another cytoplasmic protein was tyrosine phosphorylated and
      subsequently translocated to the nucleus in response to IL-2. This protein had an
      apparent molecular mass of 84 kDa and was not recognized by stat3 or stat1 mAb or
      antisera. Since IL-2 induced nuclear translocation of the 84 kDa protein and
      stat3 followed identical kinetics, p84 is a candidate for a new, yet undefined,
      member of the STAT family. Taken together, we report that IL-2 induces tyrosine
      phosphorylation and subsequent nuclear translocation of stat3 and an as yet
      undefined 84-kDa protein in antigen-specific human T cell lines.

PMID- 7528669
TI  - Recirculation, phenotype and functions of lymphocytes in mice treated with
      monoclonal antibody MEL-14.
AB  - The effect of a single injection of an antibody against the peripheral lymph node
      (PLN) homing receptor or L-selectin (gp90MEL-14) was studied in vivo in C57BL/6
      mice. L-selectin is known to be rapidly shed from leukocytes in humans and in
      mice following activation or cross-linking in vitro. Here we demonstrate that in
      vivo a single injection of MEL-14 antibody induces a rapid, almost complete and
      reversible down-regulation of L-selectin expression on both T and B cells. This
      modulation is dose dependent, specific for L-selectin and lasts for 10 days. On
      neutrophils, L-selectin expression was moderately decreased, and the injected
      antibody was detectable on the cell surface for several days. Thus, L-selectin
      expression after antibody binding in vivo was affected differently on neutrophils
      and lymphocytes. MEL-14 treatment induces profound alterations of cell traffic.
      Loss of L-selectin on lymphocytes leads to drastic PLN depletion and increased
      spleen cellularity. Depleted PLN were highly enriched in MEL-14-/lo, CD44hi and
      CD11ahi cells, which may represent transiently sessile memory/activated cells.
      The unresponsiveness in mixed lymphocyte reaction of PLN cells from treated
      animals and of purified L-selectin- PLN T cells from normal mice supports this
      view. However, PLN and spleen cells from treated animals responded normally to
      non-antigen-specific stimuli.

PMID- 7528670
TI  - The APO-1/Fas (CD95) receptor is expressed in homozygous MRL/lpr mice.
AB  - APO-1/Fas (CD95) is a transmembrane receptor that transduces apoptotic signals
      within various cells including T and B cells. The APO-1 gene was found to be
      defective in lpr mice. In these mice insertion of a retrotransposon gives rise to
      transcription of an abnormal mRNA and only a fraction of wild-type APO-1 mRNA. It
      is not clear if lpr mice still express wild-type APO-1 protein. To address this
      question, we prepared rabbit anti-APO-1 antibodies (Ab) with a peptide
      representing the extracellular sequence corresponding to residues 5-23 of APO-1.
      The rabbit Ab reacted with thymocytes from different mouse strains and the extent
      of binding was correlated with the two known APO-1 alleles. In addition, the Ab
      reacted with mouse cell lines expressing mouse APO-1 mRNA but not with human cell
      lines. Binding of the Ab to MRL and BALB/c thymocytes was completely blocked by
      the immunizing peptide. Immunofluorescence analysis of MRL/lpr thymocytes showed
      that they still express APO-1 protein at approximately one tenth of the wild-type
      expression level on their surface. In addition, in lpr as in wild-type mice we
      found a decrease of APO-1 expression in the more mature thymic compartment.
      Western blot analysis of whole cell lysates from lpr and wild-type thymocytes
      showed that the Ab recognized APO-1 in both cell types. Approximately 50% of CD3+
      splenocytes and 80% of in vitro activated CD3+ cells from wild-type mice reacted
      with the Ab, but to a lower extent than thymocytes. The same differential
      reactivity was found in lpr CD3+ splenocytes. lpr T cells, however, showed a
      substantially lower level of APO-1. Thus, the differential expression of APO-1 on
      thymic versus peripheral lpr T cells might influence their sensitivity towards
      APO-1-mediated apoptosis.

PMID- 7528671
TI  - Role of the CD40-CD40 ligand interaction in CD4+ T cell contact-dependent
      activation of monocyte interleukin-1 synthesis.
AB  - Most studies of the induction of cytokine synthesis in monocytes have employed an
      exogenous triggering agent such as lipopolysaccharide. However, in nonseptic
      inflammatory responses (e.g. rheumatoid arthritis) monocyte activation occurs as
      a result of T cell-generated signals. In previous reports, we and others have
      demonstrated that contact-dependent T cell-generated signals are capable of
      contributing to macrophage activation. We have shown that plasma membranes from
      anti-CD3 activated purified peripheral CD4+ T cells (TmA) but not from resting
      CD4+ cells (TmR) induce monocytes to synthesize interleukin (IL)-1 in the absence
      of co-stimulatory cytokines. Studies to determine the expression kinetics of the
      molecule(s) unique to activated CD4+ T cells which interact with monocytes to
      induce IL-1 revealed that optimal expression occurred at 6 h post activation.
      This matched the previously reported kinetics of expression of CD40 ligand
      (CD40L) on activated peripheral T cells, implicating the CD40-CD40L interaction
      as a candidate for the initiator of the IL-1 signaling event. The ability of TmA
      to induce IL-1 synthesis in resting monocytes could be markedly reduced by
      addition of a monoclonal anti-CD40L antibody, 5c8. In addition, a monoclonal anti
      CD40 IgM (BL-C4) proved dramatic in its ability to induce resting monocytes to
      synthesize IL-1. In summary, these results demonstrate that the CD40-CD40L
      interaction provides a critical component of CD4+ T cell contact-dependent
      activation of monocyte IL-1 synthesis.

PMID- 7528672
TI  - On the various manifestations of spontaneous autoimmune diabetes in rodent
      models.
AB  - Autoimmune (type 1) diabetes mellitus in mouse, rat, and humans shares several
      features, including T lymphocyte infiltration into pancreatic islets and a
      dependence on permissive class II major histocompatibility complex (MHC) alleles.
      We report here on an experimental model involving mice that express influenza
      hemagglutinin (HA) under the control of the insulin promoter and, at the same
      time, a transgenic class II MHC-restricted T cell receptor (TcR) specific for an
      HA peptide. These mice spontaneously develop islet infiltrates resembling those
      found in NOD mice and most animals become diabetic within 8 weeks of age. Because
      of the availability of a clonotypic TcR antibody, we can be confident that the
      Ins-HA transgene does not induce any measurable alterations in the vast majority
      of T cells with the transgenic TcR in primary and secondary lymphoid organs.
      Continuous export of large numbers of HA-specific lymphocytes from the thymus was
      not required for the manifestation of the disease since mice thymectomized at 3
      days after birth still developed the disease albeit with smaller infiltrates.

PMID- 7528673
TI  - Expression and regulation of adhesion molecules by gamma delta T cells from
      lymphoid tissues and intestinal epithelium.
AB  - T cells bearing the gamma delta T cell receptor localize largely in epithelial
      tissues, but are also present at low frequency in organized secondary lymphoid
      organs. To assess the role of cell surface adhesion molecules in the traffic and
      tissue localization of gamma delta T cells, we compared the expression of these
      molecules on both alpha beta and gamma delta T cells in several lymphoid and non
      lymphoid organs. In the gut epithelium, gamma delta cells express less LFA-1
      (CD11a), Pgp-1 (CD44), and alpha 4 integrin than the corresponding alpha beta
      cells. In lymph nodes (LN) and Peyer's patches (PP), adhesion molecule expression
      by gamma delta cells is heterogeneous, with some of the cells having a phenotype
      similar to that of intraepithelial gamma delta cells and the rest expressing high
      levels of CD44 and L-selectin (CD62L) but lower beta 7 and alpha M290, a
      phenotype more like lymph node alpha beta cells. Therefore, the particular set of
      adhesion molecules expressed by a T cell is dependent, in part, on its anatomic
      location. Superimposed upon this, however, are differences in expression that are
      based on the type of T cell; LN and PP gamma delta T cells express less CD44 but
      much more beta 7, alpha M290 and ICAM-1 (CD54) than alpha beta T cells in the
      same organ. The differences in adhesion molecules between alpha beta and gamma
      delta cells are not due simply to differences in their activation status, because
      these molecules are regulated differently after activation through the T cell
      receptor (TcR)/CD3 complex. The differential expression of adhesion molecules on
      cells bearing a particular TcR V region suggests that distinct adhesion
      phenotypes may arise from prior contact with specific antigen and resultant cell
      activation in vivo. Lastly, the presence of high level expression of alpha 4 beta
      7 and alpha M290 on L-selectinlo gamma delta cells in lymph nodes suggests that
      these gamma delta cells may be uniquely capable of migrating to the gut. The
      differences in adhesion molecule expression and regulation between gamma delta
      and alpha beta T cells could explain, in part, the distinct homing and tissue
      localization of these T cell subsets in vivo.

PMID- 7528674
TI  - Functional and molecular characterization of B cell-responsive V delta 1+ gamma
      delta T cells.
AB  - Cells expressing the V delta 1+ gene segment are a minor gamma delta T cell
      population in human peripheral blood but predominate in epithelial and (inflamed)
      tissues. The characteristic dendritic-like morphology of these gamma delta T
      cells is consistent with their putative immune surveillance role in epithelia.
      Their function, however, remains unknown. We and others previously reported that
      a subset of V delta 1+ gamma delta T cells proliferates after stimulation with
      Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (LCL), but not
      with fresh peripheral blood-derived B cells. These responses were independent of
      the type of T cell receptor (TcR) gamma chain co-expressed with the V delta 1
      chain. The in vivo relevance of this LCL-mediated activation as well as the
      nature of the stimulatory ligand on the LCL is not well established. In this
      study, we tested the proliferative response of V delta 1+ LCL-responsive T cells
      against non-EBV-transformed B cells, activated through CD40 by murine EL4 B5
      cells, and to a panel of B cell lines differing in the expression of EBV nuclear
      antigen proteins and adhesion/co-stimulatory molecules. The role of the Epstein
      Barr virus-derived antigen in the induction of this response could be excluded as
      the activated (non-EBV-transformed) peripheral blood B cells were also able to
      induce a proliferative response in the LCL-responsive V delta 1+ T cells.
      Therefore, the stimulatory ligand on B cells is of cellular rather than of viral
      origin, and its expression is up-regulated upon activation of B cells. The
      expression of B7 and CD39 molecules on the surface of activated B cells appeared
      to be crucial since antibodies to these structures could block the induction of
      proliferation of the V delta 1+ T cells. Finally, we investigated the diversity
      of the responding V delta 1+ gamma delta T cell clones by sequence analysis of
      the TcR delta junctional regions. No restricted V-D-J sequences were found among
      the LCL-responsive V delta 1+ T cell clones, arguing strongly against a mono- or
      oligoclonal V delta 1+ gamma delta T cell response to LCL. These findings may
      explain the presence of polyclonally activated V delta 1+ T cells in inflamed
      tissues where activated B cells are often present.

PMID- 7528675
TI  - Alpha 2,3-sialyl and alpha 1,3-fucosyltransferase-dependent synthesis of sialyl
      Lewis x, an essential oligosaccharide present on L-selectin counterreceptors, in
      cultured endothelial cells.
AB  - Sialyl Lewis x (sLex) oligosaccharides have been shown to be present in
      counterreceptors for L-selectin. We and others have previously shown that high
      endothelial cells in lymph nodes and at sites of inflammation express sLex. Here
      we show that also cultured human umbilical vein endothelial cells (HUVEC) express
      sLex on their cell surface. This oligosaccharide is formed by sequential action
      of alpha 2,3-sialyl- (alpha 2,3-ST) and alpha 1,3-fucosyltransferases (alpha 1,3
      FT) on N-acetyllactosamine. At least two of the several alpha 2,3-ST and four of
      the several alpha 1,3-FT are present in HUVEC. In functional assays both alpha
      2,3-ST and alpha 1,3-FT activities were observed in HUVEC lysates with exogenous
      lactosamine and sialyllactosamine acceptors, leading to the generation of the
      sialyllactosamine and sLex sequences, respectively. TNF stimulation increased the
      level of mRNA expression of FT VI, and the alpha 1,3-FT activity in HUVEC. Taken
      together these data show that endothelial cells express sLex and that they
      possess mRNA as well as enzyme activities of several alpha 2,3-ST and alpha 1,3
      FT necessary in the final steps of sLex synthesis. Furthermore, inflammatory
      cytokines such as TNF can enhance transferase activities relevant in generating
      putative L-selectin counterreceptors.

PMID- 7528676
TI  - Properties of mouse CD40. Ligation of CD40 activates B cells via a Ca(++)
      dependent, FK506-sensitive pathway.
AB  - The immunosuppressive drugs cyclosporine A (CsA) and FK506 selectively abrogate
      Ca(++)-regulated activation pathways in both T cells and B cells. We show here
      that anti-CD40-induced murine B cell proliferation, in the presence or absence of
      interleukin-4 (IL-4) is, like the response to anti-immunoglobulin (Ig), abrogated
      by 1-5 ng/ml (concentration causing 50% inhibition ca. 1 nM) FK506. However, the
      effects of the drug on proliferative responses elicited by anti-Ig or anti-CD40
      differ significantly: firstly, the response to anti-CD40 + IL-4 becomes
      completely FK506-resistant within 24 h, whilst that to anti-Ig remains sensitive
      significantly longer. Secondly, stimulating B cells concurrently via CD40,
      surface Ig (sIg) and IL-4 receptors invokes an FK506-resistant activation
      pathway. We previously reported that ligation of either sIg or CD40 receptors, in
      conjunction with IL-4, induces the transcription factor, nuclear factor of
      activated T cells (NF-AT) in B cells, via a CsA/FK506-sensitive pathway. However,
      NF-AT induction elicited by anti-Ig/anti-CD40/IL-4 is still FK506 sensitive,
      implying that the drug resistance of the response to these three stimuli involves
      additional components than NF-AT. These results indicate that CD40 activates
      murine B cells via a Ca(++)-dependent pathway. In agreement with this, anti-CD40
      induces a modest increase in intracellular Ca++ levels in these cells, which
      appears to be largely due to Ca++ influx through the plasma membrane.

PMID- 7528677
TI  - Interactions between Ca2+, PCA50941 and Bay K 8644 in bovine chromaffin cells.
AB  - We describe here the effects of PCA50941 (a novel 1,4-dihydropyridine derivative)
      comparatively with Bay K 8644 on various parameters in bovine adrenal chromaffin
      cells. The binding of [3H](+)-isradipine to bovine adrenal medulla plasma
      membranes was inhibited similarly by PCA50941 and Bay K 8644 at various [Ca2+]o
      suggesting a common binding site for both compounds on the dihydropyridine
      receptor. In voltage-clamped chromaffin cells PCA50941 (1 microM) and Bay K 8644
      (1 microM) shifted the I-V relationship of whole-cell Ca2+ currents by about 5-10
      mV towards more hyperpolarizing potentials. At -20 mV, PCA50941 enhanced ICa by
      195 +/- 16% and Bay K 8644 by 288 +/- 51%. Stimulation of fura 2-loaded
      chromaffin cell suspensions with 17.7 K+/0.5 Ca2+ increased 3-fold the basal
      [Ca2+]i. PCA50941 increased further the K(+)-evoked peak to 655 nM, and Bay K
      8644 to 1129 nM. In the presence of 5 mM Ca2+, PCA50941 or Bay K 8644 increased
      the [Ca2+] peaks to 427 and 350 nM, respectively. PCA50941 potentiated the
      release of catecholamines from perfused bovine adrenal glands evoked by 30 s
      pulses of 17.7 mM K+ in a manner dependent on the [Ca2+]o. Thus at 1, 2.5, 5 and
      10 mM Ca2+, secretion was 2.3-, 3.8-, 5- and 4-fold greater than in control
      glands. Bay K 8644 enhanced the K(+)-induced response 3- and 9-fold at [Ca2+]o of
      0.25 or 0.5 mM, respectively; at higher [Ca2+]o the potentiation was similar to
      that of PCA50941.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528678
TI  - Action of heparin and ruthenium red on responses of reversibly-permeabilised rat
      mesenteric arteries.
AB  - Heparin and ruthenium red were introduced intracellularly into rat mesenteric
      resistance arteries via reversible-permeabilisation. Heparin and ruthenium red
      inhibited contractile responses to noradrenaline, but not caffeine in Ca(2+)-free
      conditions. Neither heparin nor ruthenium red significantly inhibited peak
      contractile responses to K+, noradrenaline or caffeine in physiological saline,
      although heparin significantly increased the time taken for peak force to develop
      in response to noradrenaline. Noradrenaline and calcium concentration-response
      relationships were unaffected by heparin. Experiments with permeabilised, fura-2
      loaded vessels indicated that heparin inhibited Ca2+ release induced by
      noradrenaline, but did not inhibit caffeine-induced Ca2+ release. The peak rise
      in intracellular Ca2+ following K+, or noradrenaline in physiological saline was
      unaffected by heparin. The use of reversible permeabilisation may prove a useful
      approach, allowing introduction of a variety of membrane-impermeant blockers of
      second messenger systems into intact resistance arteries.

PMID- 7528679
TI  - Ca(2+)-dependent protein kinase C isoforms in rat pituitary hyperplasia: effect
      of in vivo treatment with quinagolide.
AB  - Ca(2+)-dependent protein kinase C (PKC) activity, diacylglycerol levels and PKC
      alpha, beta I, beta II and gamma expression were analyzed in the pituitary of
      female rats treated with estradiol alone (2 months) or in combination with
      quinagolide in the second month. Polymerase chain reaction (PCR) and Western blot
      analysis revealed the presence of PKC alpha, beta I and beta II isoenzymes in the
      rat pituitary gland but not of PKC gamma isoenzymes. Increases in pituitary
      weight and plasma prolactin levels induced by estradiol were associated with an
      increase in diacylglycerol pituitary content (1.55 +/- 0.06 versus 1.12 +/- 0.17
      nmol diacylglycerol/mg protein in controls, P < 0.01). Cotreatment with
      quinagolide reversed these effects. Changes in PKC activity were accompanied by
      parallel changes in PKC alpha and beta I expressions. Estradiol treatment
      increased the expression of these isoforms whereas cotreatment with quinagolide
      antagonized these effects. PKC beta II expression was not affected. In
      conclusion, Ca(2+)-dependent PKC activity and protein expression are increased in
      hyperplastic pituitary cells, suggesting the involvement of this class of PKCs in
      the rat pituitary cell proliferation and/or hormonal secretion. This is further
      assessed by the fact that the dopamine receptor agonist treatment decreases
      activity and expression of these PKCs in parallel with the decrease in hormonal
      secretion and cell proliferation.

PMID- 7528680
TI  - Ligand affinities at recombinant N-methyl-D-aspartate receptors depend on subunit
      composition.
AB  - The ligand preferences of recombinant NR1 homomeric and NR1-NR2 heteromeric NMDA
      receptors were examined by homogenate binding assay. The binding affinities for
      most ligands were similar to those reported for native NMDA receptors. The order
      of affinity for [3H]glutamate was NR1-NR2B > NR1-NR2A approximately NR1-NR2D >
      NR1-NR2C > NR1. NMDA had approximately equal affinity for all heteromeric types
      (Ki approximately 5 microM), but the competitive antagonists CGS 19755 (cis-4
      (phosphonomethyl)piperidine-2-carboxylic acid) and CGP 39653 (D,L-(E)-2-amino-4
      propyl-5-phosphono-3-pentenoic acid) displayed the affinity order NR1-NR2A > NR1
      NR2B > NR1-NR2D > NR1-NR2C. Binding of [3H]CGP 39653 could only be detected at
      the NR1-NR2A receptor type (Kd approximately 6 nM). The glycine site antagonist
      [3H]5,7-dichlorokynurenate bound with good affinity to all recombinant receptors
      (Kd approximately 50-100 nM), while glycine exhibited an affinity order of NR1
      NR2C >> NR1 = NR1-NR2B = NR1-NR2D > NR1-NR2A. The channel-site ligand [3H]MK 801
      ((+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen
      maleate) showed the affinity ranking NR1-NR2A = NR1-NR2B >> NR1 > NR1-NR2C = NR1
      NR2D. Thus the ligand binding affinities of recombinant NMDA receptors is
      dependent on their subunit composition. The NR1-NR2A, NR1-NR2B, NR1-NR2C and NR1
      NR2D receptors may account for the antagonist-preferring, agonist-preferring,
      cerebellar, and medial thalamic subtypes of native NMDA receptors, respectively.

PMID- 7528682
TI  - Septic shock: no correlation between plasma levels of nitric oxide metabolites
      and hypotension or lethality.
AB  - In the Wistar rat (Riv:TOX strain), Escherichia coli-derived lipopolysaccharide,
      up to 100 mg/kg, did not affect blood pressure. However, 6 h after administration
      of live E. coli or Staphylococcus aureus (a microorganism without
      lipopolysaccharide), both dosed at 12 x 10(9) colony forming units/kg, mean
      arterial blood pressure significantly decreased to 64% and 48% compared to
      control, respectively. In contrast to lipopolysaccharide, bacteria produced a
      dose-dependent lethality within 24 h. Live S. aureus increased plasma levels of
      nitric oxide metabolites (NOx) only four-fold, while both lipopolysaccharide and
      live E. coli approximately 20-fold. In conclusion, we demonstrated a lack of
      correlation between plasma NOx levels and hypotension or lethality.

PMID- 7528681
TI  - Parainfluenza virus type 3 induced alterations in tachykinin NK1 receptors,
      substance P levels and respiratory functions in guinea pig airways.
AB  - We have investigated the effects of parainfluenza virus type 3 (PI-3) on sensory
      neuropeptide levels, tachykinin receptors and their functions in guinea pig
      airways during the course of respiratory viral infection. PI-3 infected guinea
      pigs were hyperresponsive to methacholine and substance P aerosols as determined
      by earlier onset of dyspnea in these animals as compared with control on post
      inoculation day (PID) 7 but not 19. In addition, plasma protein extravasation
      produced in response to the tachykinin was increased in infected airways during
      the first week post inoculation. Infected guinea pig trachea did not respond any
      differently to methacholine when smooth muscle contraction and [3H]inositol
      phosphate accumulation were measured although the magnitude of substance P
      effects using in vitro tests was significantly greater than control on post
      inoculation day 7 but not 19. Trachea from PI-3 infected animals were
      characterized by reductions in substance P-like immunoreactivity, tachykinin NK1
      receptor number and agonist affinity during the first post-inoculation week.
      Substance P levels or tachykinin NK1 receptor numbers or affinity were not
      altered in trachea of guinea pigs 4 days after treatment with lipopolysaccharide.
      These data suggest substance P release occurs during critical periods of
      respiratory viral infection which are temporally correlated with airway
      hyperresponsiveness. Despite apparent down-regulation of tachykinin NK1
      receptors, substance P-mediated functions remained enhanced suggesting some
      alterations in post-receptor mechanisms.

PMID- 7528684
TI  - Specific changes in the basement membrane of the proximal tubules in the murine
      polycystic kidney detected by the novel anti-basement membrane monoclonal
      antibody D28.
AB  - In order to analyze renal abnormalities in mice with polycystic kidney disease
      (PKD), we produced a series of monoclonal antibodies reactive with the murine
      kidney by hybridizing P3U1 myeloma cells with spleen cells from DBA/2 mice
      immunized with the kidney of adult-type PKD mice, DBA/2FG-pcy. One clone, D28,
      reacted specifically with the basement membrane of the proximal tubules of DBA/2
      mice and DBA/2FG-pcy mice. It did not react with other parts of the murine kidney
      nor with other tissues such as the skin, ovary, fallopian tube, testis, lung and
      small intestine. While other components such as collagen IV, laminin and the core
      protein of proteoglycan could be found, the D28 epitope could not be found in the
      basement membrane of renal cysts formed in adult-type (DBA/2FG-pcy) and infant
      type (C57BL/6J-cpk) PKD mice. The D28 epitope did not, however, disappear from
      the basement membrane of proximal tubules in other types of renal abnormalities.
      These results suggest that the formation of renal cysts in the proximal tubules
      is associated with an alteration to the proximal tubule-specific structure of the
      basement membrane. The D28 monoclonal antibody should prove a useful tool with
      which to analyze basement membrane-associated abnormalities in genetic PKD.

PMID- 7528683
TI  - Electron microscopic studies on the formation of renal juxtaglomerular cell
      granules in the vitally stained mouse kidney.
AB  - Mouse renal juxtaglomerular cells (JGC) were vitally stained with neutral red,
      and then fixed with glutaraldehyde to study by electron microscopy.
      Ultrastructural observation showed a large number of characteristic low electron
      dense juxtaglomerular granules (JGG) or low dense granules (LDG) in the cytoplasm
      of JGC. Many LDG contained a flocculent material with a dense core, which was as
      dense as the contents of JGG. Two kinds of LDG were observed. One of LDG was
      surrounded by single membrane and partial membrane, and another was surrounded by
      double membranes. Some LDG did not contain electron dense flocculent material.
      LDG were surrounded by rough endoplasmic reticulum (r-ER). Alteration of Golgi
      apparatus and r-ER was observed in JGC. Golgi complex did not associate with JGG
      and LDG.

PMID- 7528687
TI  - Inducible nitric oxide synthase in human lymphomononuclear cells activated by
      synthetic peptides derived from extracellular matrix proteins.
AB  - Synthetic peptides with sequences present in extracellular matrix proteins are
      capable of causing the expression of the inducible form of nitric oxide synthase
      (iNOS), detected by immunocytochemistry, and the release of NO by human
      lymphomononuclear cells incubated in their presence. Active peptides are 15-mers
      containing a characteristic 2-6-11 motif in which the amino acid residue at
      position 2 is Leu, Ile, Val, Gly, Ala or Lys; the residue at position 6 is always
      Pro; and residue 11 is Glu or Asp. The induction of iNOS in human monocytes and
      macrophages could be involved in the cytotoxicity against tumor cell lines also
      elicited by these peptides.

PMID- 7528692
TI  - Vascular pattern in the chorioallantoic membrane (CAM) after laser/photosensitive
      compound treatment. I. Macroscopic findings.
AB  - Laser light and photosensitive compound meso-tetra(4- sulfonatophenyl)porphine
      dodecahydrate tetra-sodium salt (TPPS4) activated by laser light were used for
      examining a regressive vascular effect with focal morphological differentiation
      of chick chorioallantoic membrane (CAM). After laser/TPPS4 treatment, arrest of
      blood flow in the irradiated area of CAM was observed in all cases, followed by
      massive aggregation of erythrocytes obstructing the vessel lumina. Similar
      effects were observed under much prolonged laser radiation in the area vasculosa.
      No extravasates were found. Those findings support the concept that the
      biological effect of low power laser/TPPS4 treatment causes changes in the
      relationship between red cells, blood plasma and embryonal endothelium during
      angiogenetic processes in growing embryonal vessels.

PMID- 7528685
TI  - Is Zn2+ transported by the mitochondrial calcium uniporter?
AB  - Zinc ions were found to inhibit Ca2+ uptake by rat liver mitochondria driven by
      succinate respiration but not that by a valinomycin-induced membrane potential.
      Zn2+ at 1 microM or higher concentrations induced a lowering of the membrane
      potential under the former but not the latter conditions. It is concluded that it
      is the lowered membrane potential in the presence of Zn2+ that reduces the rate
      of respiration-driven Ca2+. Ruthenium red was found to inhibit the uptake of Zn2+
      but had no influence on its action upon the membrane potential. Zn2+ did not
      affect the Ruthenium red-insensitive Ca2+ efflux. Ca2+ stimulated the uptake of
      Zn2+. It is concluded that Zn2+ may be transported by the mitochondrial calcium
      uniporter but that it may have access to sites required for inhibition of
      respiration by other routes.

PMID- 7528689
TI  - Purified retinal nitric oxide synthase enhances ADP-ribosylation of rod outer
      segment proteins.
AB  - Nitric oxide synthase is present in different cell layers of vertebrate retina
      and seems to have neuromodulatory functions in the outer retina. The enzyme, when
      purified from a bovine retina extract, has an apparent molecular mass of 160 kDa
      and resembles the neuronal constitutive NOS type I with respect to Ca(2+)
      calmodulin sensitivity, Km value and inhibition by analogues of L-arginine.
      Retinal NOS is present in a preparation of rod outer segments attached to parts
      of the inner segments, but not in pure outer segments. We describe the
      enhancement of specific ADP-ribosylation of outer segment proteins by purified
      retinal NOS.

PMID- 7528690
TI  - The interaction between the catalytic A subunit of calcineurin and its
      autoinhibitory domain, in the yeast two-hybrid system, is disrupted by
      cyclosporin A and FK506.
AB  - The Ca(2+)-calmodulin dependent protein phosphatase, calcineurin, is thought to
      mediate the action of the two immunosuppressants, cyclosporin A (CsA) and FK506.
      Calcineurin from all species consists of a catalytic A subunit and a regulatory
      peptide B, which plays an essential role in catalysis. The enzymatic function is
      probably also regulated by an autoinhibitory domain (AID) present in the
      catalytic subunit. We have used the yeast two-hybrid system to show that the
      putative AID of the yeast catalytic subunit Cna1 binds only to truncated Cna1,
      devoid of AID. Although deletion of the genes encoding the yeast catalytic
      subunits of calcineurin (CNA1 and CNA2) maintain the interaction, absence of the
      regulatory subunit Cnb1 prevents binding. Interestingly, both CsA and FK506
      disrupt this interaction, whereas binding of Cna1 to calmodulin remains
      unaffected. This indicates that a simple cellular system, developed in yeast,
      could provide further insight into an understanding of calcineurin inhibition.

PMID- 7528688
TI  - Acute nephrotoxicity of a carcinogenic iron chelate. Selective inhibition of a
      proteolytic conversion of alpha 2U-globulin to the kidney fatty acid-binding
      protein.
AB  - The mechanism of acute nephrotoxicity of an iron chelate in vivo has been
      investigated. Administration of a renal carcinogen ferric nitrilotriacetate (Fe
      NTA) (15 mg Fe/kg body weight, intraperitoneally) led to selective loss of a
      renal protein with an apparent molecular mass of 17 kDa. Analysis of the 17 kDa
      protein by NH2-terminal sequence demonstrated its identity over 16 NH2-terminal
      residues as a kidney fatty acid-binding protein (k-FABP) that is a
      proteolytically modified form of alpha 2U-globulin, a major urinary protein of
      adult male rats. An immunochemical study using anti-alpha 2U-globulin polyclonal
      antibodies confirmed that a single injection of Fe-NTA led to a decrease in k
      FABP levels. However, a 19-kDa protein identical to the alpha 2U-globulin
      progressively appeared in the kidney, suggesting that the proteolytic processing
      of alpha 2U-globulin in the renal proximal tubules was suppressed by the
      treatment with Fe-NTA. By monitoring k-FABP and its precursor alpha 2U-globulin,
      it was determined that repeated exposure to Fe-NTA caused suppression of both
      proteolytic and endocytotic activity of the kidney. The implications of these
      data in relation to the nephrotoxicity of Fe-NTA are discussed.

PMID- 7528691
TI  - Carbohydrate moieties on sperm surface: physiological relevance.
AB  - OBJECTIVES: To study the cross-reactions between mouse monoclonal antisperm
      antibodies and somatic cells or bacteria, to identify the antigenic determinants
      responsible for such cross-reactions, and to correlate between the antibody
      function and determinant recognition. DESIGN: Activities of monoclonal antibodies
      (mAbs) were characterized by immunosorbent assay of RIA technique; sperm epitopic
      characterization was performed in lectin-blocking and sugar competitive assays
      and correlated with functional assays. SETTING: Procedures were performed in a
      university laboratory. RESULTS: The extensive cross-reactivity between antigenic
      determinants of sperm, erythrocytes, and bacteria (but not bacterial
      deglycosylated lipopolysaccharides) was observed. The analytic procedures
      indicated predominant mAb reactions to carbohydrates such as fucose, galactose,
      mannose, N-acetylglucosamine and N-acetylgalactosamine. Approximately half of the
      30 tested mAbs interfered in the functional assays, that is, sperm agglutination,
      immobilization, and zona-free penetration. CONCLUSIONS: Sperm carbohydrates seem
      to induce antibody reactions to common antigenic determinant(s) present on
      gametes, somatic cells, and infectious agents. Thus molecular mimicry between
      bacteria and sperm can be a major factor inducing antisperm immunological
      reactions. Obtained antisperm mAbs, reacting to glycosylated epitopes, presented
      very strong properties in sperm agglutination and/or immobilization. This did not
      correlate with inhibiting properties of some antibodies in xenogeneic zona-free
      penetration test, that is, this assay possibly is not based on oligosaccharide
      mediation.

PMID- 7528693
TI  - The inducible form of nitric oxide synthase (iNOS) in insulin-producing cells.
AB  - The enzyme nitric oxide synthase catalyzes the conversion of L-arginine to
      citrulline and the radical nitric oxide, a short-lived mediator which can be
      produced in a variety of cell types. Overproduction of nitric oxide is probably
      implicated in the pathogenesis of several immunologically mediated diseases,
      including insulin-dependent diabetes mellitus (Type 1). Insulin-producing cells
      exposed to cytokines, especially interleukin-1, express an inducible form of
      nitric oxide synthase which is similar to that observed in activated macrophages.
      Induction of this enzyme mRNA in these cells depends on protein synthesis, and it
      is probably modulated by protein products of early response genes, such as C-fos.
      Cytokines seem to activate beta-cell inducible-nitric oxide synthase mostly by
      stimulating mRNA transcription, but drugs such as nicotinamide and dexamethasone
      inhibit interleukin 1 induced nitric oxide production by posttranscriptional
      mechanisms. Considering the potential role for nitric oxide in beta-cell damage
      during the early stages of Type 1 diabetes, it is of high relevance to further
      characterize the regulation of this enzyme in insulin-producing cells.

PMID- 7528686
TI  - RNA synthesis inhibition stabilises urokinase mRNA in macrophages.
AB  - Urokinase-type plasminogen activator (uPA) mRNA is induced in macrophages by the
      lineage specific growth factor CSF-1. Upon removal of CSF-1 from bone marrow
      derived macrophages (BMM), uPA mRNA decayed with a half-life of 2 h. If RNA
      synthesis inhibitors actinomycin D, 5,6-dichloro-1-beta-ribofuranosyl
      benzimidazole (DRB) or alpha-amanitin were added at the time as CSF-1 removal,
      the uPA message was stabilised. This was not a general effect on CSF-1 responsive
      mRNAs, as c-myc mRNA decayed with normal kinetics in the presence of inhibitors.
      The requirement for ongoing RNA synthesis for the degradation of uPA mRNA in BMM
      suggests that a component of the degradative pathway may be induced following
      removal of CSF-1.

PMID- 7528696
TI  - CD45RO expression on circulating CD19+ B cells in Crohn's disease correlates with
      intestinal permeability.
AB  - BACKGROUND/AIMS: Increased intestinal permeability is observed in Crohn's disease
      and a subset of first-degree relatives. An alteration in isoform expression of
      the common leukocyte antigen (CD45) is also found in a significant fraction of
      patients. Because this alteration may be a measure of antigen exposure, the
      hypothesis of the study was that this alteration would be observed in both
      patients and relatives of patients with Crohn's disease and that this would
      correlate with increased intestinal permeability. METHODS: Lactulose and mannitol
      permeability were defined in healthy controls, patients with Crohn's disease, and
      their first-degree relatives. Simultaneously, peripheral blood was assayed using
      flow cytometry for CD45RO expression on CD19+ B cells. RESULTS: A subset of
      relatives had significantly increased permeability, as did the majority of
      patients with Crohn's disease. A small fraction of peripheral B cells from
      controls expressed the CD45 isoform (< 6%). This fraction was significantly
      increased for patients with Crohn's disease and their relatives. Relatives with
      no clinical evidence of Crohn's disease were only found to have increased CD45RO
      expression if they had increased permeability. CONCLUSIONS: Individuals at risk
      for developing Crohn's disease include a subset with increased intestinal
      permeability. These people have an associated phenotypic alteration of
      circulating B cells that is not observed in controls or relatives with normal
      intestinal permeability.

PMID- 7528694
TI  - Ion channels, electrical activity and insulin secretion.
AB  - The insulin-secreting pancreatic beta cell is electrically excitable and changes
      in the membrane potential play an important role in coupling the metabolism of
      glucose (and other nutrient secretagogues) to the discharge of the insulin
      containing granule. The application of the patch-clamp technique, which permits
      the recordings of the minute currents associated with the opening of individual
      ion channels, to pancreatic islet cells has revolutionized our understanding of
      the beta cell electrophysiology. Here we review some of the recent progress in
      the field. The properties of functionally important ion channels are described
      and their possible roles are discussed.

PMID- 7528697
TI  - Vascular adhesion molecule expression in viral chronic hepatitis: evidence of
      neoangiogenesis in portal tracts.
AB  - BACKGROUND/AIMS: T cell-mediated immune reactions could be crucial for
      hepatocellular damage in viral chronic hepatitis. The aims of this study were to
      compare the expression of activation and cell adhesion molecules on peripheral
      blood and intrahepatic lymphocytes from chronic hepatitis C and to analyze the
      intrahepatic expression of vascular adhesion molecules in viral chronic
      hepatitis. METHODS: Lymphocytes from patients with chronic hepatitis C were
      studied by flow cytometry. Intrahepatic expression of vascular adhesion molecules
      was assessed by immunohistochemistry. RESULTS: Liver-derived T cells showed a
      high expression of activation and cell adhesion molecules. Interestingly, we
      observed that vascular cell adhesion molecule 1 was up-regulated on both
      sinusoidal endothelial and portal dendritic cells. A novel finding was the
      neoformation of microvessels in inflamed portal tracts. An enhanced expression of
      endoglin was located on sinusoidal endothelial cells and on portal tracts.
      CONCLUSIONS: Activated cytotoxic T cells, which showed an up-regulated expression
      of cell adhesion molecules, composed the majority of intrahepatic lymphocytes in
      chronic hepatitis C. The expression of vascular cell adhesion molecule 1 on
      portal dendritic cells and the microvessels neoformation in portal tracts from
      viral chronic hepatitis could define the main pathway for the recruitment and
      priming of liver-infiltrating T cells.

PMID- 7528698
TI  - Neurogenic inflammation in the intestine.

PMID- 7528695
TI  - Insulin secretion in rats with chronic nitric oxide synthase blockade.
AB  - Nitric oxide, which is produced from L-ar-ginine by a nitric oxide-synthase
      enzyme, has been shown to be a ubiquitous messenger molecule. Recently, it has
      been suggested that nitric oxide might influence insulin secretion by activating
      the soluble guanylate cyclase and generating cyclic guanosine monophosphate
      (cGMP). We have investigated the role of the nitric oxide pathway in insulin
      secretion by evaluating the insulin response to several secretagogues in rats in
      which nitric oxide-synthase was chronically inhibited by oral administration of
      the L-arginine analogue, NG-nitro-L-arginine methyl ester (L-NAME). Blood
      pressure and aortic wall cGMP content were used as indices of nitric oxide
      synthase blockade. Insulin secretion was evaluated after an intravenous bolus of
      D-glucose, L-arginine or D-arginine. Chronic L-NAME administration induced a 30%
      increase in blood pressure and a seven-fold drop in arterial cGMP content. Body
      weight, fasting plasma glucose and insulin were not influenced by L-NAME
      administration. First-phase insulin secretion (1 + 3 min) in response to glucose
      was not significantly different in L-NAME and control rats. The areas under the
      insulin curve were similar in both groups. Insulin secretion in response to D
      arginine or L-arginine in L-NAME-treated and control rats were also similar. In
      conclusion, chronic nitric oxide-synthase blockade increases blood pressure and
      decreases aortic cGMP content, but does not alter insulin secretion in response
      to several secretagogues. Chronic oral administration of L-NAME in the rat
      provides an adequate animal model for studying the L-arginine nitric oxide
      pathway.

PMID- 7528701
TI  - Identification of dihydropyridine (DHP) binding sites on cultured monkey renal
      cells (GMRC) with a photoaffinity probe (-)-[3H]-azidopine.
AB  - The low affinity binding sites identified in crude membranes from different
      excitable tissues with the dihydropyridine (DHP) calcium (Ca2+) channel ligands
      have confused researches in the field of Ca2+ channels as they can represent low
      affinity state(s) of the DHP receptor, or they can be labelled with DHP-type Ca2+
      channel ligands. The aim of this communication was to provide more evidence for
      the existence of separate DHP binding sites on the surface of cultured green
      monkey renal cells (GMRC). The saturation ligand binding experiments with [3H]
      nitrendipine (NTP) and photoaffinity labelling studies with (-)-[3H]-azidopine
      (AZI) were performed in order to identify and further characterize the DHP
      receptor on cultured GMRC. Specific high affinity sites identified on GMRC with
      [3H]-NTP (Bmax = 0.78 +/- 0.03 pmol/mg protein and KD = 0.06 +/- 0.1 nmol/l in
      native cells) and photolabelled with AZI represent DHP receptor on L-type Ca2+
      channels. The low affinity binding sites photolabelled with AZI on GMRC (9.84 +/-
      2.4 pmol/mg protein and KD = 3.21 +/- 1.25 nmol/l in native cells) were
      significantly increased after preincubation of GMRC with low concentrations of
      DHPs nitrendipine and nisoldipine. Preincubation of GMRC with Ca2+ channel
      agonist (-)BAYK 8644 significantly reduced specific photolabelling with AZI on
      GMRC and increased low affinity labelling. Preincubation of (+)BAYK 8644 was
      without any effect. Niguldipine (DHP with the voluminous substituent on the port
      side of the DHP ring) partially inhibited specific photolabelling with AZI on
      GMRC and also partially reduced the maximal number of low affinity binding sites
      labelled with AZI. Our results support the hypothesis of separate subsites in the
      region of DHP receptor of GMRC and the existence of the "marginal" photolabelling
      of specific DHP binding sites identified on Ca2+ channels.

PMID- 7528699
TI  - Galanin contracts and relaxes guinea pig and canine intestinal smooth muscle
      cells through distinct receptors.
AB  - BACKGROUND/AIMS: Galanin induces a contraction or a relaxation of digestive
      smooth muscle. Receptors mediating these effects have not been pharmacologically
      characterized. The aim of the study was to evaluate properties of two specific
      galanin antagonists M15 and M35 on galanin effects on muscle cells. METHODS:
      Isolated muscle cells were obtained separately from circular and longitudinal
      layers of guinea pig and dog ileums. Contraction was expressed as percentage
      decrease in cell length from control. RESULTS: Galanin induced a contraction of
      cells from guinea pig circular layer (50% effective concentration [EC50], 80
      pmol/L) and dog longitudinal layer (EC50, 100 pmol/L). The antagonists inhibited
      galanin-induced contraction. The most potent was M15 (50% inhibitory
      concentration [IC50], 80 pmol/L in guinea pig; 90 pmol/L in dog) which was > M35
      (IC50, 4 nmol/L in guinea pig; 1 nmol/L in dog). In dog circular layer, galanin
      inhibited cholecystokinin-induced contraction by relaxing the cells (EC50, 3
      pmol/L). The antagonists inhibited this relaxation. The most potent was M35
      (IC50, 60 pmol/L) which was > M15 (IC50, 900 pmol/L). CONCLUSIONS: Galanin
      antagonists M15 and M35 inhibit the contraction and the relaxation induced by
      galanin with different potency, suggesting the presence of distinct galanin
      receptors in gastrointestinal tract that each mediates a specific effect.

PMID- 7528700
TI  - Mucosal expression by B7-positive cells of the 60-kilodalton heat-shock protein
      in inflammatory bowel disease.
AB  - BACKGROUND/AIMS: Heat-shock protein (Hsp) 60 is an immunodominant antigen of
      mycobacteria and other microorganisms that is highly homologous to its human
      counterpart. Hsp60 may provide a link between immunity to invading microorganisms
      and autoimmune diseases. METHODS: Expression of Hsp60 was studied by
      immunohistochemistry in gut resection specimens of patients with Crohn's disease
      (n = 14), ulcerative colitis (n = 7), acute self-limited colitis (infective type)
      (n = 5), and controls (n = 9) using the monoclonal antibodies LK1 and LK2.
      RESULTS: A strong staining positivity for Hsp60 was observed in numerous
      mononuclear cells of the mucosa and submucosa in ileum and colon tissue biopsy
      specimens of patients with Crohn's disease from inflamed and healthy areas. In
      ulcerative colitis, Hsp60 expression was limited to the mucosa. In biopsy
      specimens from patients with acute self-limited colitis and controls, Hsp60
      positive cells were absent or only present in low numbers and staining intensity
      was weak. Differentiation between mammalian and bacterial Hsp60 showed expression
      of the human homologue. Double staining for B7 and Hsp60 showed that Hsp60 was
      expressed by B7-positive cells. CONCLUSIONS: Human Hsp60 is strongly expressed by
      B7-positive antigen-presenting mononuclear cells in the mucosa of patients with
      inflammatory bowel disease and might play a role in the initiation or maintenance
      of the inflammatory process.

PMID- 7528702
TI  - L-type calcium channels may fill directly the IP3-sensitive calcium store.
AB  - The relationship between inositol-1,4,5-trisphosphate-sensitive Ca2+ stores and
      Ca2+ entry through potential-dependent L-type Ca2+ channels was examined using
      whole-cell voltage-clamp technique in cells of longitudinal muscle layer of
      guinea-pig ileum. It was found that heparin (10(-10) mol/l) in the pipette
      rapidly inhibited the current through L-type Ca2+ channels. Neither an inhibitor
      of the sarcoplasmic reticulum Ca2+ pump (cyclopiazonic acid) nor blockers of
      Ca(2+)-induced Ca2+ release (ryanodine or ruthenium red) affected the Ca2+
      current. The failure of heparin to affect Ca(2+)-currents through L-type Ca2+
      channels in cells from circular muscle of the same organ suggested that heparin
      had no direct effect on L-type Ca2+ channels. Thus the inhibition of the latter
      in heparin-loaded cells from the longitudinal layer is supposed to be Ca(2+)
      dependent due to the overfilling of the inositol-1,4,5-trisphosphate-sensitive
      Ca2+ store.

PMID- 7528703
TI  - Evolution of patient care, education, and research in asthma by one academic team
      of investigators over 35 years: the Northwestern University Medical School
      Division of Allergy-Immunology experience (Part Two).
AB  - This report reviews approximately 35 years of patient care, teaching, and
      research an asthma in one academic unit at Northwestern University Medical
      School. Historical perspectives are summarized on the delivery of care for
      asthma, therapeutic regimens for asthma we believed in (and were wrong), and
      diagnosis and management in the last decade of this century. Particular problems,
      such as potentially fatal asthma and assessment and management of such problems,
      are discussed. Finally, certain aspects of our basic research programs and their
      relevance to asthma are briefly reviewed. Part One of this article appeared in
      the May-June issue of this journal.

PMID- 7528704
TI  - Long-term effects of alpha-interferon therapy for type II mixed cryoglobulinemia.
AB  - BACKGROUND: Several reports showed that mixed cryoglobulinemia (MC) is closely
      associated with hepatitis C virus (HCV) infection. Since several authors reported
      the efficacy of alpha-interferon in the treatment of MC, we investigated the long
      term effects of this drug on clinical, hematological and virological parameters
      in a group of 18 patients (13 women and 5 men, mean age 56 +/- 11 years) affected
      by MC. METHODS: A bone marrow biopsy was performed in all patients, and a liver
      biopsy was obtained in those with biochemical signs of chronic liver disease. The
      presence of HCV-RNA in serum was assessed by detection of anti-HCV antibodies and
      by PCR amplification of the 5' untranslated region of HCV. All patients followed
      the same treatment schedule: three million units of recombinant interferon alpha
      2b s.c., three times a week for 1 year. RESULTS: In 5 cases bone marrow histology
      showed the presence of a monoclonal lymphocytic infiltrate. Liver biopsies were
      performed in 13 (72%) of the patients and a chronic liver disease was found in
      all 13. Anti-HCV antibodies were present in 17 (95%) subjects. HCV-RNA was
      detected in all cases (100%) before therapy. Five (28%) patients achieved a
      complete response and 9 (50%) a partial response, while the others (4 cases, 22%)
      showed minor responses. Four patients cleared the virus and obtained a complete
      remission of the MC. CONCLUSIONS: HCV may be a cause of MC. The disease is
      associated with a high incidence of monoclonal lymphocytic infiltrate of the bone
      marrow. Alpha-interferon seems to be an effective agent for the treatment of MC.

PMID- 7528705
TI  - Antibodies to hepatitis C virus in thalassemia.
AB  - The presence of anti-HCV antibodies has been examined in a group of 256
      consecutive thalassemic patients who received blood transfusions in several
      countries around the world. Overall 60% were found to be anti-HCV positive. A
      higher incidence of anti-HCV antibodies was noted in Italian patients with
      respect to patients living in Eastern countries, and in southern Italy with
      respect to northern Italy. Because these patients received a large portion of
      their transfusions before the anti-HCV test became available, these data indicate
      a higher anti-HCV seroprevalence among Italian blood donors and confirm published
      data indicating a higher seroprevalence in southern Italy. The anti
      seropositivity correlated highly with serum transaminase elevation and with
      histological diagnoses of chronic active hepatitis.

PMID- 7528706
TI  - [Molecular virology founded models of anti-HIV therapy].
AB  - Apart from the enzyme reverse transcriptase, which is characteristic of
      retroviruses, a number of other steps in the replication cycle of the human
      immunodeficiency virus (HIV) represent potential targets for chemotherapeutic
      attack. These include adsorption of the virus particle onto the cell surface, the
      uncoating of the viral capsid, integration of the proviral DNA into the cell
      genome, maturation of viral proteins, and the assembly and release of viral
      progeny. In addition, certain viral regulatory proteins (Tat, Rev, etc.,
      represent novel targets for specific anti-HIV treatment. The development of drugs
      leading to activation of the intracellular anti-viral mechanism also seems to
      hold out promise of success.

PMID- 7528707
TI  - Growth hormone (GH) stimulates insulin-like growth factor-I (IGF-I) and IGF
      binding protein (IGFBP)-2 gene expression in spleens of juvenile rats.
AB  - Growth and development of the spleen involves the growth hormone (GH)/insulin
      like growth factor-I (IGF-I) axis. To evaluate the molecular mechanism of these
      effects we studied the effect of hypophysectomy (Hx) and GH replacement therapy
      on the expression of IGF-I, the IGF-I receptor and IGF-binding protein-2 (IGFBP
      2) in juvenile rats. Hx resulted in a 30% reduction in body weight. GH
      replacement therapy for seven days partially prevented these effects. IGF-I mRNA
      levels were reduced 30% by Hx, IGFBP-2 mRNA levels fell 50% whereas IGF-I
      receptor mRNA levels were unaffected. GH therapy prevented the reduction in IGF-I
      and IGFBP-2 mRNA levels. These results suggest that the GH effect on splenic
      growth and development is via local (paracrine) IGF-I expression, in addition to
      any effect by circulating (endocrine) IGF-I.

PMID- 7528708
TI  - Increased gene expression of water channel in cirrhotic rat kidneys.
AB  - In patients with liver cirrhosis, impaired water and sodium excretion has been
      incriminated in the pathogenesis of ascites formation. Increased reabsorption of
      water in the distal nephron has been shown to play an important role in water
      retention in cirrhotic rat kidneys. Recently, a complementary DNA (cDNA) for the
      vasopressin-regulated water channel (the aquaporin of the apical membrane of the
      kidney collecting duct [AQP-CD]) has been cloned. It is suggested that AQP-CD
      plays an important role in renal water handling. Therefore, in the present study,
      to investigate the pathogenic role of the water channel in water retention in
      liver cirrhosis, gene expression of AQP-CD in the kidney was evaluated in
      cirrhotic rats. Liver cirrhosis was induced by an intraperitoneal administration
      of carbon tetrachloride twice a week for 12 weeks in 14 rats. Messenger RNA
      expression of AQP-CD in whole kidney homogenates determined by Northern blot
      hybridization was significantly increased in cirrhotic rats (147%; P < .01) and
      dehydrated rats (206%; P < .0001) compared with control rats. Protein expression
      of AQP-CD in the homogenates of kidney medulla determined by Western blot
      analysis was significantly increased in cirrhotic rats (203%; P < .03) compared
      with control rats. Furthermore, mRNA expression of AQP-CD in the kidney showed a
      significant correlation with the volume of ascites in cirrhotic rats (r = .62, P
      < .02). No significant difference was observed in water intake, urinary volume,
      serum osmolality, serum sodium, and creatinine clearance between control and
      cirrhotic rats, suggesting that dehydration was unlikely in cirrhotic
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528709
TI  - Predictive value of precore hepatitis B virus mutations in spontaneous and
      interferon-induced hepatitis B e antigen clearance.
AB  - We previously reported two mutually exclusive mutations in the precore region of
      hepatitis B virus: M1 (T-1856, proline-serine substitution at codon 15) and M2 (A
      1896, stop codon at codon 28). This study was conducted to determine if the
      presence of precore mutants affect spontaneous or interferon (IFN)-induced
      hepatitis B e antigen (HBeAg) clearance. Sera from 201 hepatitis B e antigen
      positive Chinese patients (including 106 who participated in a controlled trial
      of IFN therapy) with chronic hepatitis B virus (HBV) infection were analyzed by
      direct sequencing of HBV DNA after amplification by polymerase chain reaction
      (PCR) assay. Forty-three (21%) patients had M1 (T-1856), and 20 patients (10%)
      had M2 (A-1896). During a follow-up period of 1 to 7 years, 75%, 28%, and 26% of
      those with M2 (A-1896), M1 (T-1856), and wild type sequence respectively, cleared
      HBeAg (P < .0001). Eighteen (67%) of 27 patients with wild-type sequence but none
      of 10 patients who had M1 (T-1856) in their initial samples developed M2 (A-1896)
      after loss of HBeAg (P < .0001). Sustained antiviral response was achieved in
      55%, 0%, and 17% of interferon-treated patients who had M2 (A-1896), M1 (T-1856),
      and wild-type sequence, respectively, initially (P = .04). However, patients with
      M2 (A-1896) were also more likely to have elevated pretreatment aminotransferase
      levels (P = .02). In summary, HBeAg-positive Chinese patients with M2 (A-1896)
      were mor likely to clear HBeAg, and to do so earlier.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7528710
TI  - Determination of hepatitis delta virus RNA by polymerase chain reaction in acute
      and chronic delta infection.
AB  - The objective of this study was to evaluate the usefulness of hepatitis delta
      virus (HDV) RNA detection by polymerase chain reaction (PCR) in acute and chronic
      D hepatitis and to correlate with HDV-RNA detection by dot blot and hepatic delta
      antigen. Serum samples from 33 patients with acute hepatitis B surface antigen
      (HBsAg)-positive hepatitis (15 with hepatitis B and D coinfection, 8 with HDV
      superinfection, and 10 with acute hepatitis B), 85 patients with chronic HBsAg
      positive hepatitis (73 with chronic D hepatitis and 12 with chronic B hepatitis),
      and consecutive serum samples from nine patients with chronic D hepatitis treated
      with interferon alfa-2b were studied. HDV-RNA was detected by PCR in 93% of the
      patients with hepatitis B and D coinfection, in 100% of the patients with
      hepatitis D superinfection, and in 1 of the 10 patients with acute hepatitis B
      who subsequently seroconverted to total antibody to hepatitis delta antigen
      (HDAg), whereas HDV-RNA was found by dot blot technique in 60% of the hepatitis B
      and D coinfection cases, in 62.5% of the patients with hepatitis D
      superinfection, and in none of the acute hepatitis B cases. In chronic D
      hepatitis, HDV-RNA tested positive by PCR assay in 97% of patients with
      intrahepatic HDAg, in one patient with undetectable hepatic HDAg, and in none of
      the patients with chronic hepatitis B. In the treated patients, HDV-RNA was
      observed to become negative by PCR only in the three patients who had a
      persistent response to interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528711
TI  - Plasma levels of substance P in liver cirrhosis: relationship to the activation
      of vasopressor systems and urinary sodium excretion.
AB  - The mediators of the hyperdynamic circulation of liver cirrhosis are not well
      characterized. Substance P is a potent vasodilatory peptide produced by the
      enteric nervous system and partly cleared by the liver. In this work we have
      investigated the plasma levels of substance P and their relationship to the
      hemodynamic, neurohormonal, and renal function changes occurring in patients with
      cirrhosis. Seven healthy subjects (control group), 7 cirrhotic patients without
      ascites (group I), and 24 cirrhotic patients with ascites (group II) were
      studied. Cardiac output (CO), femoral blood flow (FBF), blood volume (BV),
      femoral arteriovenous difference of oxygen content (Ca-v O2), plasma renin
      activity (PRA), plasma aldosterone concentration (PAC), and plasma norepinephrine
      (NE) were determined. Five patients underwent trans-jugular intrahepatic porto
      systemic stent shunt (TIPSS) because of refractory ascites. Immunoreactive
      substance P (irSP) was measured by radioimmunoassay after plasma extraction. irSP
      was higher in ascitic patients than in healthy controls (P < .01) and directly
      correlated with PRA, PAC, plasma NE, and Pugh's score and was inversely
      correlated with urinary sodium excretion, glomerular filtration rate, and Ca-v
      O2. No differences were observed between portal and peripheral vein irSP
      concentration. TIPSS placement induced a decrease in portal pressure and an
      increase in CO but circulating irSP remained unchanged. Our data show that
      circulating irSP is increased in decompensated cirrhotic patients and may be
      involved in the pathogenesis of the hemodynamic changes of cirrhosis. Alleviation
      of portal hypertension did not result in decreased plasma levels of this
      vasodilatory substance.

PMID- 7528712
TI  - Early cellular rejection after orthotopic liver transplantation correlates with
      low concentrations of FK506 in hepatic tissue.
AB  - We have previously reported that low hepatic tissue cyclosporine levels correlate
      with early cellular rejection after liver transplantation. The aim of this study
      is to determine whether there is a similar relationship in patients treated with
      FK506. Twenty-five liver biopsies were performed in 10 patients immunosuppressed
      with FK506 without cellular rejection: day 7 = 10; day 14 = 3; day 21 = 9; day 28
      = 1; day 35 = 1; and day 42 = 1. These 10 patients without cellular rejection
      were compared with 7 patients immunosuppressed with FK506 with cellular rejection
      who underwent a total of 23 liver biopsies, including 9 biopsies that showed
      rejection: day 7 = 4; day 14 = 2; day 21 = 1; day 28 = 1; and day 49 = 1. There
      was no significant difference between the nonrejection and current rejection
      groups in the median plasma concentration of FK506, 0.9 ng/mL versus 0.9 ng/mL (P
      = .50). In contrast, the median hepatic tissue concentration of FK506 was
      significantly higher in the nonrejection group than it was in the current
      rejection group, 144 ng/g versus 48 ng/g (P = .02). In the current rejection
      group, 7 of 9 hepatic tissue concentrations of FK506 were < 100 ng/g, and in the
      nonrejection group, 18 of 25 hepatic tissue concentrations were > 100 ng/g. Low
      hepatic tissue concentrations of FK506 correlate with the occurrence of early
      cellular rejection after liver transplantation, in contrast to plasma
      concentrations of FK506. A hepatic tissue concentration of FK506 < 100 ng/g is
      78% sensitive and 72% specific for cellular rejection.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7528714
TI  - [16S rRNA reverse transcription-polymerase chain reaction of leptospires].
AB  - We amplified the leptospiral RNAs of Leptospira interrogans serovar lai strain
      Lai and L. biflexa serovar patoc strain Patoc I, extracted by the method of SiO2
      high concentration salt solution (8 mol/L GuHCl) absorption, with the 16S rRNA
      gene primers of Leptospira interrogans by reverse transcription-polymerase chain
      reaction (RT-PCR). It demonstrated that the detecting sensitivity by naked eye
      after electrophoresis could be 100 times higher when we amplified DNA and RNA of
      leptospires at the same time by RT-PCR.

PMID- 7528713
TI  - [Confirmative test of human semen stain and mixed stain by immunohistochemical
      method using anti-human sperm monoclonal antibodies].
AB  - The stain of the human semen, the mixture of the human semen and vaginal
      secretion as well as the semen of the bull, goat, pig, dog, rabbit, rat and mouse
      was examined by the immunohistochemical method using anti-human sperm monoclonal
      antibodies (SMAB). The result revealed that the SMAB E10 could make a distinction
      between the human semen, the mixture of the human semen and vaginal secretion,
      and the seven kinds of animal semen. It is concluded that this method can be used
      for the species identification of the semen and the mixed stain under the general
      condition.

PMID- 7528715
TI  - [Effect of excessive fluoride intake on mental work capacity of children and a
      preliminary study of its mechanism].
AB  - We made an investigation in 157 children, aged 12-13, born and grew up in a coal
      burning pattern endemic fluorosis area and an experiment on excessive fluoride
      intake in rat. The results showed: (1) Excessive fluoride intake since early
      childhood would reduce mental work capacity (MWC) and hair zinc content: (2) The
      effect on zinc metabolism was a mechanism of influence on MWC by excessive
      fluoride intake; (3) Excessive fluoride intake decreased 5-hydroxy indole acetic
      acid and increased norepinephrine in rat brain; whether this is also a mechanism
      of the influence on MWC awaits confirmation.

PMID- 7528716
TI  - [Therapeutic effectiveness of zuzhongping on patients with arteriosclerostic
      cerebral infarction].
AB  - Forty-six patients with acute arteriosclerostic cerebral infarction were randomly
      divided into two groups: control group and treatment group. Each of them included
      23 patients respectively. The patients in the control group were given Dextran-40
      but the ones in the treatment group were given the mixture of Zuzhongping. The
      course of treatment was 3 weeks. It was found that there was a significant
      difference (P < 0.01) in the score percentage, before and after treatment of
      neurological defects, between the control group and the treatment group, and the
      former (29.70 +/- 33.52) was much lower than the latter (45.40 +/- 27.60). The
      total curative rate of the treatment group (87.0%, 20/23) was significantly
      higher than that of the control group (60.9%, 14/23). There was an obviously
      prolonged KPTT (kaolin partial thromboplastin time) value and a decreased Fb
      (fibrinogen) level in the treatment group. Before treatment they were 32.43 +/-
      4.03 sec and 6.18 +/- 1.77 g/L respectively, but after treatment, 52.96 +/- 10.50
      sec and 4.5 +/- 0.95 g/L respectively. The authors suggest that the significant
      therapeutic efficacy of Zuzhongping in the patients with acute arteriosclerostic
      cerebral infarction is related to its action of anticoagulation, modification of
      PGI2 and TXA2 level in the body, decreased blood Fb level, hyperglycemia, etc.

PMID- 7528717
TI  - The upstream promoter of the beta-amyloid precursor protein gene (APP) shows
      differential patterns of methylation in human brain.
AB  - The human beta-amyloid protein precursor (beta-APP) gene (symbol APP) shows
      variable levels of expression in different human tissues, including brain.
      Because at least a moderate level of beta-APP expression is probably a necessary,
      although not sufficient, condition for diseases associated with pathologic
      deposition of beta-APP proteolytic products (such as the A beta peptide), we
      sought to identify factors in the 5' promoter of the human APP gene that may
      regulate tissue-specific expression of the APP gene. We report that sequences
      upstream from -500 bp in the APP promoter display complex, tissue-specific
      patterns of methylation. Furthermore, different patterns of methylation were
      observed even in DNA from different regions of brain. These differentially
      methylated sequences are able to bind nuclear proteins expressed in brain and
      HeLa cells and are also methylated in neocortex of nonhuman primates. Because
      these methylation patterns crudely reflect differences in APP expression, they
      may represent one mechanism for the tissue-specific regulation of APP expression.

PMID- 7528719
TI  - Characterization of neutralizing monoclonal antibodies directed against
      Staphylococcus aureus alpha-toxin.
AB  - A panel of neutralizing murine monoclonal antibodies (MAbs) against
      Staphylococcus aureus alpha-toxin has been established, using formaline
      inactivated alpha-toxin as an immunogen. Five independent groups of neutralizing
      epitopes have been identified representing five functionally important structures
      in the toxin molecule. Because none of the antibodies binds to overlapping
      decapeptides representing the toxin sequence or to bromocyanogen cleavage
      products of alpha-toxin, they may all bind to conformational epitopes.
      Nevertheless, they all bind to monomeric alpha-toxin in a Western blot. Three of
      the antibodies bind to the toxin monomer in an enzyme-linked immunosorbent assay
      (ELISA) in the presence, but not in the absence, of detergent. These epitopes are
      not accessible in hexameric toxin; two of them may represent the contact sites of
      the toxin monomers upon hexamerization and one is related to a structurally
      important glycine-rich central hinge region. Two different antibodies bind to
      monomeric toxin in an ELISA in the presence and absence of detergent and their
      epitopes are present more than once on oligomeric toxin; they bind strongly to
      hexameric toxin in a Western blot. The binding properties of the antibodies to
      alpha-toxin in different assay systems are summarized in an epitope model, which
      describes the presence of neutralizing domains in the different conformational
      steps required for pore formation.

PMID- 7528718
TI  - A YAC contig spanning a cluster of human type III receptor protein tyrosine
      kinase genes (PDGFRA-KIT-KDR) in chromosome segment 4q12.
AB  - We have mapped five genes encoding protein tyrosine kinases (PTKs) to the
      pericentromeric region of human chromosome 4. PTK4 and TYRO4, which encode
      nonreceptor intracellular PTKs, are located at 4p12 and 4q13, respectively. The
      other three genes, PDGFRA, KIT, and KDR, encode type III transmembrane receptor
      PTKs for known ligands. We have developed a contig of 29 yeast artificial
      chromosomes (YACs) spanning approximately 2 Mb of DNA at 4q12 that includes
      PDGFRA, KIT, and KDR, and we have used this YAC contig to map 12 different
      sequence-tagged sites in this region. PDGFRA, KIT, and KDR thus constitute a
      cluster of genes at 4q12 encoding closely related type III receptor PTKs.
      Mutations of the human KIT gene result in piebaldism, an autosomal dominant
      disorder of melanocyte development.

PMID- 7528720
TI  - Monoclonal antibody 1D8 detects an activation-related molecule on human B
      lymphocytes and on a minor T-lymphocyte subpopulation.
AB  - A novel murine monoclonal antibody (MAb) 1D8 was produced after immunization with
      the nylon wool-adherent fraction of human peripheral blood mononuclear cells
      (PBMNC). Its reactivity pattern was studied on a panel of hemopoetic normal
      cells, cell lines and malignancies. Mab 1D8 detects a lymphocyte-specific surface
      antigen expressed on a major subpopulation of mature B lymphocytes as well as on
      a minor T-cell subset. Activation-related changes in the expression of 1D8
      molecule were observed on both B and T lymphocytes. As compared with the pattern
      of known activation-associated antigens, 1D8 seems to play a role in the early
      stages of lymphocyte activation. The antigen could not be immunoprecipitated by
      the conventional methods for glycoproteins.

PMID- 7528721
TI  - Modulation of adhesion molecule expression on endothelial cells by verapamil and
      other Ca++ channel blockers.
AB  - Cytokine-induced expression of adhesion molecules on leukocytes and endothelial
      cells (EC) is a crucial point in the process of organ transplant rejection. It
      has been shown that protein kinase C (PKC) is involved in this activation
      process. Verapamil and other calcium channel blockers seem to possess
      immunosuppressive qualities in vivo and in vitro; some authors suggested that
      this is due to PKC- or calmodulin-antagonism. Thus our objectives were to further
      investigate the second-messenger systems involved in the stimulation of EC and to
      analyze whether the beneficial influence of calcium channel blockers on the
      outcome of transplantation is due to impaired expression of adhesion molecules on
      EC. Our results, obtained in an in vitro model using human umbilical vein EC,
      show that IL-1-induced expression of intercellular adhesion molecule-1 (ICAM-1)
      is in part mediated by PKC and that parallel activation of calmodulin is
      required. Expression of ICAM-1 was reduced to 38.5% by PKC-inhibitor H7 and to
      77.2% by calmodulin-inhibitor W7. In addition, data on the intracellular events
      in TNF-alpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1) is
      presented, showing that both PKC and, to a higher extent, calmodulin, are
      involved in this process. Expression of VCAM-1 was reduced to 63.7% by H7 and to
      27.7% by W7. IL-1-induced expression of endothelial leukocyte adhesion molecule-1
      (ELAM-1) is PKC-dependent but insensitive to blocking of calmodulin. Though
      activation of adhesion molecule expression utilizes PKC and/or calmodulin as
      second-messenger pathways the investigated calcium channel blockers verapamil (R-
      and S-enantiomers), diltiazem and Ro 40-5967 failed to inhibit adhesion molecule
      expression. Surprisingly, higher concentrations of verapamil (> 12.5
      micrograms/ml) or Ro 40-5967 (5 micrograms/ml) significantly enhanced IL-1
      induced expression of ELAM-1. ICAM-1-expression was also enhanced by verapamil,
      but not by Ro 40-5967 or diltiazem. This enhancement was only seen if verapamil
      was added maximally one hour after the cytokine stimulus indicating that
      transcriptional modulation is responsible for the observed effects. Our findings
      indicate that calcium channel blockers have an immunomodulating effect
      independent of adhesion molecule expression.

PMID- 7528723
TI  - Was exposure to directly antiviral cytokines during primary infection an
      important selective pressure in the evolution of unique immune evasion strategies
      by viruses?
AB  - Different virus families are characterized by various immune evasion strategies.
      These viruses have co-evolved with an increasingly sophisticated mammalian immune
      system which has continually placed pressure on their continued survival. This
      paper proposes that exposure to directly antiviral cytokines, namely TNF and
      members of the IFN family, during inflammatory and early immune responses,
      exerted particularly strong selective pressures on viruses, and has had a
      critical influence on the development of viral immune evasion strategies and
      pathogenesis. In the context of antiviral cytokine activity, this report
      concentrates on two DNA virus families with contrasting pathogenic and immune
      evasion strategies, namely poxviruses and HSV.

PMID- 7528722
TI  - The L-selectin (Leu8) molecule is associated with the TcR/CD3 receptor;
      fluorescence energy transfer measurements on live cells.
AB  - Several accessory molecules were shown to play important roles in T cell
      functions and be in close proximity to the T cell receptor (TcR/CD3). The L
      selectin molecule (Leu8, LAM1-1, LECAM1) also plays an important role in
      lymphocyte homing and proliferation. We were interested in determining the
      proximity of this molecule to the TcR/CD3 complex on live peripheral human T
      cells. Using a fluorescence energy transfer method, designed to study individual
      cells, we could show that L-selectin is within 170 A of the TcR/CD3 complex.
      Monoclonal antibody directed against the LAM1-1 (Leu8) epitope of the L-selectin
      molecule suppressed the mitogenic activity of antibodies specific for various CD3
      epitopes in vitro. Intracellular Ca2+ mobilization obtained with wt31 followed by
      cross-linking antibody or with anti-CD3 was not influenced by anti-Leu8 antibody.
      Also antibody directed against the LAM1-1 epitope did not influence the binding
      of the mitogenic antibodies, as shown by fluorescence-based flow cytometry.
      Therefore, we suggest that binding of TcR/CD3 bound mitogenic antibodies to
      accessory cell Fc receptors may be hindered by antibodies bound to the close
      proximity L-selectin molecules.

PMID- 7528724
TI  - Primate terminal complement inhibitor homologues of human CD59.

PMID- 7528725
TI  - A new DRB1*1202 allele (DRB1*12022) found in association with DQA1*0102 and
      DQB1*0602 in two black narcoleptic subjects.

PMID- 7528726
TI  - cDNA sequence and chromosome localization of pig alpha 1,3 galactosyltransferase.
AB  - Human serum contains natural antibodies (NAb), which can bind to endothelial cell
      surface antigens of other mammals. This is believed to be the major initiating
      event in the process of hyperacute rejection of pig to primate xenografts. Recent
      work has implicated galactosyl alpha 1,3 galactosyl beta 1,4 N-acetyl
      glucosaminyl carbohydrate epitopes, on the surface of pig endothelial cells, as a
      major target of human natural antibodies. This epitope is made by a specific
      galactosyltransferase (alpha 1,3 GT) present in pigs but not in higher primates.
      We have now cloned and sequenced a full-length pig alpha 1,3 GT cDNA. The
      predicted 371 amino acid protein sequence shares 85% and 76% identity with
      previously characterized cattle and mouse alpha 1,3 GT protein sequences,
      respectively. By using fluorescence and isotopic in situ hybridization, the GGTA1
      gene was mapped to the region q2.10-q2.11 of pig chromosome 1, providing further
      evidence of homology between the subterminal region of pig chromosome 1q and
      human chromosome 9q, which harbors the locus encoding the AB0 blood group system
      as well as a human pseudogene homologous to the pig GGTA1 gene.

PMID- 7528727
TI  - Analysis of HLA-DMB mutants and -DMB genomic structure.
AB  - The HLA-DM locus encodes class II-like A and B chains and apparently regulates
      the antigen presentation function of conventional major histocompatibility
      complex (MHC) class II molecules. Here we describe the HLA-DMB mutations in three
      presentation defective B lymphoblastoid cells lines (B-LCL), 7.19.6, 10.6.6, and
      10.78.6, which express DMB transcripts of abnormal length. Mutant 7.19.6 has a C-
      >T point mutation that introduces a 5' splice site into exon 3 of DMB. The
      independently derived mutants, 10.6.6 and 10.78.6, each harbor a G-->A mutation
      in exon 3 and also lack an identical downstream segment of RNA. Mapping of DMB
      intron/exon borders, using a genomic clone, revealed that the segment missing in
      mutants 10.6.6 and 10.78.6 represents the fourth exon of DMB; no mutations were
      found within exon 4 in either 10.6.6 or 10.78.6, however. In addition, the DMB
      gene was found to have a six exon genomic structure, typical of MHC class II B
      genes.

PMID- 7528728
TI  - Molecular cloning of the gene coding for the mouse T-cell antigen CD7.

PMID- 7528729
TI  - Cytokines and progenitor cells of granulocytopoiesis in peripheral blood of
      patients with bacterial infections.
AB  - To investigate the physiological role of granulocyte colony-stimulating factor (G
      CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the
      adaptation mechanisms of myelopoiesis to enhanced demand, we studied both
      cytokines and their myeloid target cells in hematologically healthy patients
      suffering from acute bacterial infections. Endogenous serum levels of G-CSF and
      GM-CSF, granulocyte-macrophage colony-forming cell (GM-CFC) concentrations, and
      differential counts were determined for the peripheral blood of 57 patients with
      clinically apparent bacterial infections (26 males and 31 females aged 16 to 89
      years) and 18 healthy controls (8 males and 10 females aged 23 to 84 years).
      Patients were selected for acute-phase protein and at least two additional
      clinical signs reflecting a bacterial infection. Patients showed significantly
      higher numbers of myeloid progenitor cells than controls (median, 68 versus 26 GM
      CFC/ml; P < or = 0.01). G-CSF but not GM-CSF levels were found to be elevated (>
      or = 50 to 863 pg/ml). In the acute stage of infection, progenitor and cytokine
      levels were not influenced by gender, differences in therapy, or localization of
      the infection. Progenitor and G-CSF levels were not associated with absolute
      neutrophil counts or C-reactive protein. However, a negative correlation between
      number of GM-CFC per milliliter and age (R = -0.47; P < or = 0.001) and an
      inverse relationship between the incidence of high GM-CFC concentrations and
      elevated G-CSF levels (phi = -0.34; P < or = 0.01) were found. Combining both
      parameters into a cytokine-progenitor pattern, we observed a highly significant
      age-dependent response of myelopoiesis to inflammation (P < or = 0.001). Younger
      patients had high progenitor counts (> 75 GM-CFC/ml) associated with G-CSF levels
      below 50 pg/ml, whereas for the older patients, the reverse pattern was
      predominant. The results indicate that the age-dependent myelopoietic response to
      acute bacterial infections is characterized by an inverse relationship between
      progenitor cells and G-CSF. The observed cytokine-progenitor patterns could have
      implications for therapy with G-CSF and the prognosis of infectious diseases.

PMID- 7528732
TI  - Diminished priming of neonatal polymorphonuclear leukocytes by lipopolysaccharide
      is associated with reduced CD14 expression.
AB  - Previous research in our laboratory has shown that polymorphonuclear leukocytes
      (PMN) from neonates are not primed effectively in vitro with lipopolysaccharide
      (LPS) (from Escherichia coli 0111:B4) compared with priming of adult PMN. This
      finding led us to speculate that differences between neonatal and adult LPS
      receptors may account for the lower response by neonatal PMN to LPS. In these
      experiments, we investigated if CD14 or other LPS receptors contribute to the
      priming activity of PMN by LPS. We found that unprimed neonatal and adult PMN
      expressed similar numbers of CD14 (11.6 +/- 9.2 versus 18.6 +/- 2.7 fluorescence
      units [FlU]; P > 0.05) and LPS-binding sites (2.94 +/- 1.4 versus 4.94 +/- 0.79
      FlU; P > 0.05). Monoclonal antibody against CD14 (MY4) did not significantly
      change the binding of LPS to adult unprimed PMN, suggesting that LPS receptors
      other than CD14 receptors are predominant on PMN. However, when PMN were
      pretreated with LPS (10 ng/ml) for 45 min at 37 degrees C, expression of CD14 on
      adult PMN increased to 33.8 +/- 4.9 FlU (P < 0.05 versus unprimed adult PMN)
      while that on neonatal PMN showed little change, increasing to 17.2 +/- 10.3 FlU
      (P > 0.05 versus unprimed neonatal PMN; P < 0.05 versus primed adult PMN).
      Furthermore, MY4 specifically blocked oxidative-radical production from PMN
      primed with LPS (10 ng/ml) compared with that from control PMN (P < 0.01). These
      studies suggest that LPS primes PMN by activating CD14 expression. We conclude
      that lower expression of CD14 or failure to up-regulate CD14 after LPS
      pretreatment contributes to the inability of neonatal PMN to be primed by LPS.

PMID- 7528731
TI  - Avirulence of rough mutants of Shigella flexneri: requirement of O antigen for
      correct unipolar localization of IcsA in the bacterial outer membrane.
AB  - Mutations in the lipopolysaccharide (LPS) of Shigella spp. result in attenuation
      of the bacteria in both in vitro and in vivo models of virulence, although the
      precise block in pathogenesis is not known. We isolated defined mutations in two
      genes, galU and rfe, which directly affect synthesis of the LPS of S. flexneri
      2a, in order to determine more precisely the step in virulence at which LPS
      mutants are blocked. The galU and rfe mutants invaded HeLa cells but failed to
      generate the membrane protrusions (fireworks) characteristic of intracellular
      motility displayed by wild-type shigellae. Furthermore, the galU mutant was
      unable to form plaques on a confluent monolayer of eucaryotic cells and the rfe
      mutant generated only tiny plaques. These observations indicated that the mutants
      were blocked in their ability to spread from cell to cell. Western immunoblot
      analysis of expression of IcsA, the protein essential for intracellular motility
      and intercellular spread, demonstrated that both mutants synthesized IcsA,
      although they secreted less of the protein to the extracellular medium than did
      the wild-type parent. More strikingly, the LPS mutants showed aberrant surface
      localization of IcsA. Unlike the unipolar localization of IcsA seen in the wild
      type parent, the galU mutant expressed the protein in a circumferential fashion.
      The rfe mutant had an intermediate phenotype in that it displayed some
      localization of IcsA at one pole while also showing diffuse localization around
      the bacterium. Given the known structures of the LPS of wild-type S. flexneri 2a,
      the rfe mutant, and the galU mutant, we hypothesize that the core and O-antigen
      components of LPS are critical elements in the correct unipolar localization of
      IcsA. These observations indicate a more precise role for LPS in Shigella
      pathogenesis.

PMID- 7528733
TI  - Reconstituted high-density lipoprotein neutralizes gram-negative bacterial
      lipopolysaccharides in human whole blood.
AB  - We have tested hypotheses relating lipoprotein structure to function as measured
      by the relative ability to neutralize endotoxin by comparing natural human
      lipoproteins, a chemically defined form of reconstituted high-density lipoprotein
      (R-HDL), and a lipid emulsion (Intralipid). The human whole-blood system was used
      as an in vitro model of lipopolysaccharide (LPS) binding protein and CD14
      dependent activation of cytokine production. When lipoproteins were compared on
      the basis of protein content, R-HDL was most effective in reducing tumor necrosis
      factor alpha (TNF-alpha) production followed in order by very low density
      lipoprotein, low-density lipoprotein, Intralipid, and natural HDL. However, when
      these particles were compared by protein, phospholipid, cholesterol, or
      triglyceride content by stepwise linear regression analysis, only phospholipid
      was correlated to effectiveness (r2 = 0.873; P < 0.0001). Anti-CD14 monoclonal
      antibodies MY4 and 3C10 inhibited LPS binding protein and CD14-dependent
      activation of TNF-alpha production by LPS at LPS concentrations up to
      approximately 1.0 ng/ml. R-HDL (2 mg of protein per ml) blocked TNF-alpha
      production by LPS from both smooth- and rough-type gram-negative bacteria at
      concentrations up to 100 ng of LPS per ml but had little effect on heat-killed
      gram-positive Staphylococcus aureus and no effect on other LPS-independent
      stimuli tested. These results support our hypothesis that LPS is neutralized by
      binding to phospholipid on the surface of R-HDL and demonstrate that R-HDL is a
      potent inhibitor of the induction of TNF-alpha by LPS from both rough- and smooth
      form gram-negative bacteria in whole human blood.

PMID- 7528730
TI  - Biologic activities of antibodies to the neutral-polysaccharide component of the
      Pseudomonas aeruginosa lipopolysaccharide are blocked by O side chains and mucoid
      exopolysaccharide (alginate).
AB  - Virulent strains of Pseudomonas aeruginosa are either of a nonmucoid,
      lipopolysaccharide (LPS)-smooth or mucoid, LPS-rough phenotype, and immunity to
      these different variants is efficiently mediated by antibodies specific to O
      antigens or mucoid exopolysaccharide (also called alginate), respectively. In
      addition to O side chains and core polysaccharide components, the LPS of P.
      aeruginosa also contains neutral-polysaccharide components that express antigenic
      determinants common to many clinical isolates. We evaluated antibodies specific
      to neutral polysaccharides for the ability to mediate opsonic killing and
      protective immunity. Antibodies to these antigens mediated opsonic killing of
      poorly virulent nonmucoid LPS-rough isolates but not of isogenic strains with
      either a LPS-smooth or a mucoid phenotype. Antibodies to neutral-polysaccharide
      antigens also failed to protect neutropenic mice from challenge with modest doses
      of LPS-smooth P. aeruginosa strains (< 10(3) CFU per mouse), whereas O-antigen
      specific antibodies were highly protective. Antibodies to neutral polysaccharides
      deposited significantly (P = 0.002) more C3 onto LPS-rough strains than did
      antibodies to O side chains, but this situation was reversed when isogenic LPS
      smooth strains were tested. Given that protective immunity against P. aeruginosa
      must be directed against either nonmucoid LPS-smooth strains or mucoid LPS-rough
      strains, it appears that antibodies specific to neutral-polysaccharide antigens
      do not protect against P. aeruginosa infection. Lack of protection is likely due
      to the ability of both O side chains and mucoid exopolysaccharide (alginate) to
      interfere with the opsonic killing activity of neutral-polysaccharide-specific
      antibodies.

PMID- 7528734
TI  - The capsule and O antigen in Vibrio cholerae O139 Bengal are associated with a
      genetic region not present in Vibrio cholerae O1.
AB  - Vibrio cholerae O139 Bengal, although closely related to V. cholerae O1 El Tor,
      produces a polysaccharide capsule and has a distinct O antigen. We have
      identified a chromosomal region of at least 11 kb, as defined by three TnphoA
      mutations, that is required for the expression of both polysaccharides. Electron
      microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis show
      that these TnphoA mutants have lost the abilities both to express capsule and to
      produce lipopolysaccharide beyond the core oligosaccharide. Reactivity with O139
      typing serum and resistance to serum are also lost in the mutants. DNA probes for
      this region do not hybridize with O1 V. cholerae but do react with other vibrios,
      implying that the region was recently acquired.

PMID- 7528735
TI  - CD14 and tissue factor expression by bacterial lipopolysaccharide-stimulated
      bovine alveolar macrophages in vitro.
AB  - The membrane-associated CD14 receptor (mCD14) is a monocyte/macrophage
      differentiation antigen, and it has been demonstrated to serve as a receptor for
      bacterial lipopolysaccharide (LPS; endotoxin). Binding of LPS to mCD14 has been
      shown to be associated with LPS-induced macrophage, monocyte, and neutrophil
      activation in humans. In this report, we describe the presence and function of an
      mCD14-like receptor on bovine alveolar macrophages (bAM). An immunofluorescence
      technique and flow cytometric analysis indicated binding of anti-human CD14
      monoclonal antibodies (MAb) My4, 3C10, and 60bd to bAM. Binding of anti-CD14 MAb
      (3C10 and MY4) was reduced over 20% by pretreatment of bAM with
      phosphatidylinositol-specific phospholipase C (0.5 to 1.0 U/ml), indicating that
      bovine mCD14 is a glycosyl phosphatidylinositol-anchored protein. In addition,
      pretreatment of bAM with anti-CD14 MAb decreased binding of 125I-labeled LPS to
      macrophages, suggesting that bovine mCD14 serves as a receptor for LPS. A cDNA
      probe based on the human sequence for CD14 was used in Northern (RNA) blot
      analysis, and hybridization to human monocyte CD14 yielded the expected 1.5-kb
      band. Hybridization to bovine mRNA yielded a 1.5-kb band plus an unexpected 3.1
      kb band. Constitutive expression of bovine CD14 mRNA was observed, and the
      expression level was modestly elevated in bAM stimulated for 24 h with LPS (1
      ng/ml) in the presence of bovine serum. The function and activation of bAM were
      assessed by quantitation of tissue factor (TF) expression on the cells using an
      activated factor X-related chromogenic assay and S-2222 substrate. LPS (1 ng/ml)
      mediated upregulation of TF expression on bAM was dependent on the presence of
      bovine serum components, and TF expression was inhibited by anti-CD14 MAb. In
      addition, TF mRNA levels in LPS-stimulated bAM were decreased by pretreatment of
      cells with anti-CD14 MAb (MAb 60bd, 10 micrograms/ml).

PMID- 7528736
TI  - Modulation of transcription of rRNA genes by rapamycin.
AB  - Lymphosarcoma P1798 cells undergo growth arrest when exponentially growing
      cultures are exposed to 1 micrograms/ml of Rapamycin (Rapa). This growth arrest
      is accompanied by inhibition of RNA biosynthesis as measured by incorporation of
      3H-uridine into the newly synthesized RNA. Approximately 50% inhibition of 3H
      uridine incorporation was observed, upon exposure of P1798 cells to 1
      microgram/ml Rapa for 24 h. Run-on transcription experiments using nuclei from
      Rapa-treated cells indicated a dose-dependent inhibition of transcription or rRNA
      genes. Cells were relieved from this inhibition of transcription when Rapa was
      removed from the medium. Under similar conditions, transcriptions of U3 snRNA
      genes remained unaffected. Cytoplasmic extracts prepared from P1798 cells treated
      with 1 microgram/ml Rapa for 24 h failed to support transcription from cloned
      mouse rRNA promoter. This treatment does not affect the RNA polymerase I activity
      of P1798 cells. Addition of a highly purified murine transcription initiation
      factor specific for RNA polymerase I reconstitutes the extracts from Rapa-treated
      P1798 cells. Our data indicate that this new immunosuppressive agent modulates
      transcription of rRNA genes via regulation of specific transcription factor
      function.

PMID- 7528737
TI  - Scar formation in the vestibular sensory epithelium after aminoglycoside
      toxicity.
AB  - Hair cell degeneration and the repair process due to differing types of trauma
      have been studied extensively in the organ of Corti. It has been determined that,
      during scar formation, after differing types of trauma to the auditory sensory
      system, the reticular lamina is maintained with adherens junctions and tight
      junctions. We investigated the repair process within the vestibular epithelium.
      Hair cell degeneration was induced by the unilateral application of streptomycin
      to the inner ears of guinea pigs. Whole mount preparations of all five vestibular
      organs were processed and examined by fluorescence, light and electron
      microscopy. Scar formation was seen as early as 4 days post-treatment with
      streptomycin and was noted to coincide with hair cell degeneration. Neighboring
      supporting cells swelled and filled the space beneath the degenerating hair cell.
      Between three and five supporting cells participate in the reparative process.
      The distribution of cytokeratin is also altered during scar formation. The area
      once occupied by the hair cell becomes filled with cytokeratin-rich processes of
      supporting cells. It appears that differing numbers of supporting cells are
      involved in the reparative process within the vestibular sensory epithelium as
      compared to the auditory system. The reticular lamina remains intact at all
      times. This may possibly prevent mixing of fluids between different compartments
      in the inner ear and dysfunction of the vestibular sensory organs.

PMID- 7528740
TI  - A novel C-terminal domain in the thyroid hormone receptor selectively mediates
      thyroid hormone inhibition.
AB  - Resistance to thyroid hormone (RTH) action is due to mutations in the beta
      isoform of the thyroid hormone receptor (TR-beta). RTH patients display
      inappropriate central secretion of thyrotropin-releasing hormone (TRH) from the
      hypothalamus and thyrotropin (TSH) from the anterior pituitary in association
      with abnormal peripheral tissue responses to thyroid hormone. Whether TR-beta
      mutations cause a selective form of RTH, which only leads to abnormal pituitary
      TSH secretion (PRTH), is unclear. In a patient with PRTH, a novel mutation of a
      conserved arginine residue adjacent to the ninth heptad of TR-beta selectively
      disrupts TR homodimer formation. The mutant TR displays normal or enhanced
      function on stimulatory thyroid hormone response elements found in peripheral
      tissues, but has defective function on inhibitory thyroid hormone response
      elements found in the TRH and TSH subunit genes and explains the PRTH phenotype.
      This is the first report of a mutation in a member of the nuclear receptor
      superfamily that selectively abolishes hormone-dependent inhibition and localizes
      a novel C-terminal domain necessary for this property.

PMID- 7528744
TI  - The beta D-sheet residues of the Lck-derived SH2 domain determine specificity of
      the interaction with tyrosine-phosphorylated ligands in Ramos B cells.
AB  - Src homology 2 (SH2) domains are noncatalytic regions that are conserved among a
      group of cellular signaling proteins. SH2 domains share the common property of
      binding phosphotyrosine-containing peptides. Previously, we showed that SH2
      domains expressed as recombinant glutathione S-transferase-fusion proteins (GST
      SH2) from GTPase-activating protein, Shc, zeta-chain-associated protein tyrosine
      kinase Zap-70, and Src-like tyrosine kinases precipitated distinct sets of
      phospho-proteins from activated B cells. To determine the intrinsic structural
      motifs responsible for the binding specificity within the different SH2 domains,
      we created chimeric SH2 domains especially focusing on crystal structure-defined
      contact residues. Recombinant SH2 domains of Lck, Zap-70, and Shc were tested in
      Ramos B cell lysates for phosphotyrosine-dependent protein binding. Biomolecular
      interaction analysis (BIAcore) was used to characterize the interaction between
      the various recombinant SH2 molecules and defined phosphorylated peptides. In
      agreement with the crystal structure data from the Src and the Lck SH2 domains,
      our results show that most of the "specificity information" of the Lck SH2 domain
      is provided by the beta D-sheet, located downstream of the SH2 conserved
      consensus motif GTFLVRES. In addition, the overall affinity is critically
      influenced by residues located at the N terminus of the SH2 domain.

PMID- 7528739
TI  - Immunohistochemical localization of keratan sulfate and chondroitin 4- and 6
      sulfate proteoglycans in subregions of the tectorial and basilar membranes.
AB  - Proteoglycans containing keratan sulfate (KSPG) and 4- and 6-sulfated epitopes of
      chondroitin sulfate (CSPG) were identified in distinct domains of the tectorial
      and basilar membranes by ultrastructural immunogold labeling with monoclonal
      antibodies. In the tectorial membrane (TM), the highest concentration of gold
      particles was present in the upper fibrous layers of the limbal, middle and
      marginal zones with all three antibodies. Reactivity with anti-KSPG exceeded that
      with anti-4S and anti-6S CSPG, especially in the marginal zone. The cover net
      showed no reactivity for any antibody. Labeling density of gold particles with
      all three antibodies increased markedly from base to apex. In the basilar
      membrane (BM), all three PGs were most highly concentrated in regions of
      amorphous ground substance bordering the upper and lower filamentous bands. As in
      the TM, reactivity for anti-KSPG in the BM exceeded that for either CSPG antibody
      and staining with all three antibodies was stronger and more widespread in the
      apical as compared to the basal turns. These results provide the first
      ultrastructural demonstration of KSPG and CSPG in distinct subregions of the TM
      and BM. The preferential distribution and marked increase in PGs from base to
      apex in both TM and BM supports a role for these macromolecules in regulating
      structural and mechanical properties of these highly specialized extracellular
      membranes.

PMID- 7528742
TI  - Characterization of the complete genomic structure of the human versican gene and
      functional analysis of its promoter.
AB  - Versican is a modular proteoglycan involved in the control of cellular growth and
      differentiation. To understand versican gene regulation and transcriptional
      control, we have isolated genomic clones spanning the entire gene locus including
      5'- and 3'-flanking sequences. Versican was encoded by 15 exons encompassing over
      90 kilobase pairs of continuous DNA. The exon organization corresponded to the
      protein subdomains encoded by homologous proteins, with a remarkable conservation
      of exon size and intron phase. We discovered an additional exon just proximal to
      the glycosaminoglycan-binding region that was identical to a recently identified
      splice variant of versican (Dours-Zimmermann, M.T., and Zimmermann, D.R. (1994)
      J. Biol. Chem. 269, 32992-32998). The versican promoter harbored a typical TATA
      box located approximately 16 base pairs upstream of the transcription start site
      and binding sites for a number of transcription factors involved in regulated
      gene expression. This promoter was shown to be highly functional in transiently
      transfected cells of both mesenchymal and epithelial origin. Stepwise 5'
      deletions identified a strong enhancer element between -209 and -445 base pairs
      and a strong negative element between -445 and -632 base pairs. This study
      provides the molecular basis for discerning the transcriptional control of the
      versican gene and offers the opportunity to investigate genetic disorders linked
      to this important human gene.

PMID- 7528743
TI  - A cyclin-dependent kinase homologue, p130PITSLRE is a phosphotyrosine-independent
      SH2 ligand.
AB  - Src-homology 2 (SH2) domains are conserved, globular protein modules that mediate
      assembly of multicomponent signaling complexes. Phosphoproteins from the B
      lymphoid cell line A20 were isolated by SH2 affinity chromatography; the peptide
      sequence from one of these proteins was used to molecularly clone several related
      complementary DNAs whose predominant protein product, p130PITSLRE, is an abundant
      serine/threonine kinase with ubiquitous expression in murine tissues. The
      sequence of a previously described cyclin-dependent kinase homologue, p58clk-1,
      is entirely contained within the p130PITSLRE sequence. Specific binding of
      p130PITSLRE to SH2 domains is mediated by a serine- and glutamic acid-rich
      cluster of amino acids in the N-terminal region. This interaction is dependent on
      serine/threonine phosphorylation but independent of tyrosine phosphorylation.
      Binding is inhibited by free phosphotyrosine and by a phosphotyrosine-containing
      peptide from polyoma middle T antigen, suggesting that the p130PITSLRE binding
      site in the SH2 domain overlaps the region that binds phosphotyrosine-containing
      peptides. Bacterially expressed p130PITSLRE fragments acquire the ability to bind
      an SH2 domain when phosphorylated in vitro with casein kinase II. A subset of
      casein kinase II phosphorylation sites may therefore constitute a phosphotyrosine
      independent class of SH2 ligands.

PMID- 7528738
TI  - Nitric oxide synthase is an active enzyme in the spiral ganglion cells of the rat
      cochlea.
AB  - Nitric oxide (NO) mediates the effects of the excitatory amino acids in the
      central nervous system. Excitatory amino acids, in particular L-glutamate, are
      thought to be the neurotransmitter(s) present at the cochlear hair cell-afferent
      nerve synapse. To our knowledge, no studies to date have documented the presence
      of NO in the cochlea nor attempted to elucidate the role of NO in hearing. Rat
      cochlea frozen sections were examined for the presence of nitric oxide synthase
      (NOS) by NADPH diaphorase histochemistry. Vibratome sections of rat cochlea were
      examined by immunocytochemistry with an antibody to citrulline, an indication of
      NOS activity. Spiral ganglion cells in the rat cochlea were positive by NADPH
      diaphorase histochemistry and by anti-citrulline immunocytochemistry. These
      results indicate that NOS is present and that the enzyme actively produces nitric
      oxide in the spiral ganglion cells of the rat cochlea. Given our current
      understanding of neurotransmission in the cochlea, it is reasonable to postulate
      that the actions of NO in cochlear neuronal tissue are similar to the actions of
      NO in the CNS and that NO acts as a neurotransmitter/neuromodulator in the
      cochlea. In addition, because NO has been implicated as a mediator of
      excitotoxicity in the CNS, NO may play a role in neurotoxicity in the cochlea.

PMID- 7528745
TI  - Structural organization of the human neuronal nitric oxide synthase gene (NOS1).
AB  - Neuronal nitric oxide (NO) synthase, localized to human chromosome 12, uniquely
      participates in diverse biologic processes; neurotransmission, the regulation of
      body fluid homeostasis, neuroendocrine physiology, control of smooth muscle
      motility, sexual function, and myocyte/myoblast biology, among others.
      Restriction enzyme mapping, subcloning, and DNA sequence analysis of
      bacteriophage- and yeast artificial chromosome-derived human genomic DNA
      indicated that the mRNA for neuronal NO synthase is dispersed over a minimum of
      160 kilobases of human genomic DNA. Analysis of intron-exon splice junctions
      predicted that the open reading frame is encoded by 28 exons, with translation
      initiation and termination in exon 2 and exon 29, respectively. Determination of
      transcription initiation sites in brain poly(A) RNA with primer extension
      analysis and RNase protection revealed a major start site 28 nucleotides
      downstream from a TATA box. Sequence inspection of 5'-flanking regions revealed
      potential cis-acting DNA elements: AP-2, TEF-1/MCBF, CREB/ATF/c-Fos, NRF-1, Ets,
      NF-1, and NF-kappa B-like sequences. Diversity appears to represent a major theme
      apparent upon analysis of human neuronal NO synthase mRNA transcripts. A
      microsatellite of the dinucleotide variety was detected within the 3'
      untranslated region of exon 29. Multiple alleles were evident in normal
      individuals indicating the existence of allelic mRNA sequence variation.
      Characterization of variant human neuronal NO synthase cDNAs indicated the
      existence of casette exon 9/10 and exon 10 deletions as examples of structural
      mRNA diversity due to alternative splicing. The latter deletion of a 175
      nucleotide exon introduces a frame-shift and premature stop codon indicating the
      potential existence of a novel NH2 terminus protein. In summary, analysis of the
      human neuronal NO synthase locus reveals a complex genomic organization and mRNA
      diversity that is both allelic and structural.

PMID- 7528746
TI  - The rat hepatic lectin 1 subunit of the rat asialoglycoprotein receptor is a
      phosphoprotein and contains phosphotyrosine.
AB  - The rat asialoglycoprotein receptor (ASGPR) is an integral transmembrane
      glycoprotein composed of three polypeptide subunits, designated rat hepatic
      lectins (RHL) 1, 2, and 3. Each subunit contains one or more Ser and Thr residues
      in its cytoplasmic domain that are potential sites of phosphorylation; in
      addition, RHL1 also contains one cytoplasmic Tyr. Based on [32P]PO4 metabolic
      radiolabeling experiments, Takahashi et al. (Takahashi, T., Nakada, H., Okumura,
      T., Sawamura, T., and Tashiro, Y. (1985) Biochem. Biophys. Res. Commun. 126, 1054
      1060) concluded that RHL2 and RHL3 are phosphoproteins but that RHL1 is not. We
      report here that RHL1 in active ASGPR is, in fact, a phosphoprotein. Western blot
      analysis using anti-Tyr(P) antibody identified Tyr(P) in RHL1 of affinity
      purified ASGPRs. RHL2 and RHL3, which do not contain Tyr in their cytoplasmic
      domains, did not react with this antibody. When isolated hepatocytes were
      radiolabeled metabolically with [32P]PO4, RHL1, RHL2, and RHL3 became
      radiolabeled. Each ASGPR subunit was radiolabeled to a similar extent in the
      presence or absence of the ligand asialo-orosomucoid, indicating that functioning
      of the ASGPR does not change its steady-state 23P-radiolabeling. Phosphoamino
      acid analysis of radiolabeled ASGPR subunits identified Ser(P) as the predominant
      (approximately 95%) and Thr(P) as a minor (approximately 5%) phosphoamino acid in
      each polypeptide and confirmed the presence of Tyr(P) (approximately 1%) in RHL1.
      Furthermore, treatment of hepatocytes with 3 mM vandate at 37 degrees C for 30
      min doubled the steady-state level of Tyr(P) in RHL1.

PMID- 7528741
TI  - Synthesis of prostaglandin H synthase-2 by human alveolar macrophages in response
      to lipopolysaccharide is inhibited by decreased cell oxidant tone.
AB  - We previously demonstrated that lipopolysaccharide (LPS) increases expression of
      the prostaglandin H synthase-2 (PGHS-2) gene (Hempel, S.L., Monick, M.M., and
      Hunninghake, G.W. (1994) J. Clin. Invest. 93, 391-396). In this study, the
      expression of the PGHS-2 gene in response to changes in cell oxidant tone was
      studied. During LPS exposure, inhibition of synthesis of the free radical, NO.,
      resulted in a small decrease in prostaglandin E2 synthesis that did not reach
      statistical significance. There was no effect on enzyme mass or mRNA. In
      contrast, incubation of alveolar macrophages in the presence of LPS plus the
      antioxidant pyrrolidine dithiocarbamate, the spin trap 5,5-dimethyl-1-pyrroline-N
      oxide, or hypoxia, resulted in near complete inhibition of prostaglandin E2
      synthesis, PGHS-2 enzyme synthesis, and gene transcription of PGHS-2 mRNA. There
      was no evidence of cytotoxicity. These results demonstrate that synthesis of PGHS
      2 in response to LPS is inhibited by agents that decrease cell oxidant tone.

PMID- 7528747
TI  - Human ubiquitin-activating enzyme, E1. Indication of potential nuclear and
      cytoplasmic subpopulations using epitope-tagged cDNA constructs.
AB  - The ubiquitin-activating enzyme E1 catalyzes the first step in the ubiquitin
      conjugation pathway. Previously, we have cloned and sequenced the cDNA for human
      E1. Expression of the E1 cDNA in the ts20 cell line, which harbors a thermolabile
      E1, abrogated the phenotypic defects associated with this line. However, little
      is known of the cell biology of the E1 protein or the nature of the E1 doublet.
      Thus, we constructed epitope-tagged E1 cDNAs in which the HA monoclonal antibody
      epitope tag sequence (from influenza hemagglutinin and recognized by the 12CA5
      monoclonal antibody) was fused to the amino terminus of E1. Because the amino
      terminal amino acid sequence of E1 is unknown, three constructs were made in
      which the HA tag was placed at each of the first three ATGs in the open reading
      frame (HA-1E1, HA-2E1, and HA-3E1). Western analysis of HeLa cells transfected
      with the constructs revealed that HA-1E1 closely comigrated with the upper band
      of the E1 doublet, and HA-2E1 comigrated with the lower band of the E1 doublet;
      HA-3E1 appeared smaller than either of the E1 bands. Metabolic labeling with 32P
      and immunoprecipitation with anti-HA antibody revealed that only the HA-1E1
      protein product is phosphorylated; polyclonal anti-E1 antibody showed that only
      the upper band of the endogenous E1 doublet is phosphorylated. Each of the
      constructs was able to rescue the mutant phenotype of the ts20 cell line.
      Immunofluorescence studies showed that HA-2E1 and HA-3E1 were distributed in the
      cytoplasm with both negative and positive nuclei. This pattern of distribution
      has also been observed when immunostaining with a monoclonal antibody to E1
      (1C5). However, the staining pattern associated with a polyclonal anti-E1
      antibody (JJJ) is characterized by positive staining cytoplasm and nuclei in all
      cells. The HA-1E1 construct exhibited apparently exclusive nuclear distribution
      in HeLa cells. The difference between the staining patterns of the polyclonal and
      monoclonal anti-E1 antibodies can be explained by the existence of two
      subpopulations of E1: one cytoplasmic and partially nuclear, and one that is
      nuclear. Deletion of a small region at the amino terminus of the HA-1E1,
      including the basic sequence KKRR, transformed its immunostaining pattern to that
      observed with HA-2E1.

PMID- 7528748
TI  - Presenting joint kinematics of human locomotion using phase plane portraits and
      Poincare maps.
AB  - Additional graphical tools are needed to better visualize the joint kinematics of
      human locomotion. Standard plots in which the joint displacements are plotted
      against time or percent gait cycle do not provide sufficient information about
      the dynamics of the system. In this article, a study based on the two graphical
      tools of nonlinear dynamics to visualize the steady-state kinematics of human
      gait is presented. An experimental setup was developed to acquire the necessary
      data for application of the techniques. Twenty young adults, whose medical
      histories are free of gait pathology, were tested. Computerized
      electrogoniometers and foot switches were used to measure the kinematic data of
      the lower extremities and capture four instants of the gait cycle: heel strike,
      foot flat, heel off, and toe off. Phase plane portraits of each joint were
      constructed for the sagittal plane by plotting angular velocity against angular
      displacement. Poincare maps were obtained by periodically sampling the joint
      profiles at toe off and plotting the ith iterate against the (i + 1)th one. Phase
      plane portraits are useful in monitoring the variations of joint velocity and
      position on the same graph in a more compact form. Poincare maps are effective in
      differentiating steady gait from transient locomotion.

PMID- 7528749
TI  - The mucin epiglycanin on TA3/Ha carcinoma cells prevents alpha 6 beta 4-mediated
      adhesion to laminin and kalinin and E-cadherin-mediated cell-cell interaction.
AB  - TA3/Ha murine mammary carcinoma cells grow in suspension, do not adhere to
      extracellular matrix molecules, but do adhere to hepatocytes and form liver
      metastases upon intraportal injection. Recently we showed that the integrin alpha
      6 beta 4 on the TA3/Ha cells is involved in adhesion to hepatocytes. However,
      despite high cell surface levels of alpha 6 beta 4, TA3/Ha cells do not adhere to
      the alpha 6 beta 4 ligands laminin and kalinin. Here we show that this is due to
      the mucin epiglycanin that is highly expressed on TA3/Ha cells. Some monoclonal
      antibodies generated against epiglycanin induced capping of most of the
      epiglycanin molecules. TA3/Ha cells treated with these mAb did adhere to laminin
      and kalinin, and an epithelial monolayer was formed on kalinin, with alpha 6 beta
      4 localized in HD1-containing hemidesmosome-like structures and E-cadherin at the
      cell-cell contact sites. Similar results were obtained after treatment of TA3/Ha
      cells with O-sialoglycoprotein endopeptidase which removes all epiglycanin. In
      addition, the enzyme induced E-cadherin-mediated cell-cell aggregation. Both
      treatments also enhanced the adhesion to hepatocytes, but given the potent
      antiadhesive effect of epiglycanin it is remarkable that nontreated TA3/Ha cells
      adhere to hepatocytes at all. We found that during this interaction, epiglycanin
      was redistributed. We conclude that epiglycanin can completely prevent both
      intercellular and matrix adhesion, but that this effect can be overcome in
      certain intercellular interactions because of the induced redistribution of the
      mucin.

PMID- 7528751
TI  - Tenascin-C expression by fibroblasts is elevated in stressed collagen gels.
AB  - Chick embryo fibroblasts cultured on a collagen matrix exert tractional forces
      leading to the contraction of unrestrained, floating collagen gels and to the
      development of tension in attached, restrained gels. On a restrained, attached
      collagen gel the fibroblasts synthesize large quantities of tenascin-C, whereas
      in a floating, contracting gel tenascin-C synthesis is decreased. This regulation
      of tenascin-C synthesis can be observed by the secretion of metabolically labeled
      tenascin-C into the conditioned medium, as well as by the deposition of tenascin
      C into the collagen matrix as judged by immunofluorescence. Regulation appears to
      occur at the transcriptional level, because when cells on attached or floating
      collagen gels are transfected with promoter constructs of the tenascin-C gene,
      luciferase expression driven by the tenascin-C promoter parallels the effects
      measured for endogenous tenascin-C synthesis, whereas luciferase expression under
      the control of the SV40 promoter does not depend on the state of the collagen
      gel. The promoter region responsible for tenascin-C induction on attached
      collagen gels is distinct from the region important for the induction of tenascin
      C by serum, and may define a novel kind of response element. By joining this
      tenascin-C sequence to the SV40 promoter of a reporter plasmid, its activity can
      be transferred to the heterologous promoter. We propose that the tenascin-C
      promoter is directly or indirectly activated in fibroblasts generating and
      experiencing mechanical stress within a restrained collagen matrix. This may be
      an important aspect of the regulation of tenascin-C expression during
      embryogenesis as well as during wound healing and other regenerative and
      morphogenetic processes.

PMID- 7528750
TI  - The A-domain of beta 2 integrin CR3 (CD11b/CD18) is a receptor for the hookworm
      derived neutrophil adhesion inhibitor NIF.
AB  - The A-domain is a approximately 200-amino acid peptide present within
      structurally diverse proadhesive proteins including seven integrins. A
      recombinant form of the A-domain of beta 2 integrins CR3 and LFA-1 has been
      recently shown to bind divalent cations and to contain binding sites for protein
      ligands that play essential roles in leukocyte trafficking to inflammatory sites,
      phagocytosis and target cell killing. In this report we demonstrate that the
      neutrophil adhesion inhibitor, NIF produced by the hookworm Ancyclostoma caninium
      is a selective CD11b A-domain binding protein. NIF bound directly, specifically
      and with high affinity (Kd of approximately 1 nM) to recombinant CD11b A-domain
      (r11bA). The binding reaction was characterized by rapid association and very
      slow dissociation, and was blocked by an anti-r11bA monoclonal antibody. No
      binding was observed to rCD11aA. The NIF-r11bA interaction required divalent
      cations, and was absent when the mutant r11bA D140GS/AGA (that lacks divalent
      cation binding capacity) was used. The NIF binding site in r11bA was mapped to
      four short peptides, one of which being an iC3b binding site. The interaction of
      NIF with CR3 in intact cells followed similar binding kinetics to those with
      r11bA, and occurred with similar affinity in resting and activated human
      neutrophils, suggesting that the NIF epitope is activation independent. Binding
      of NIF to CR3 blocked its ability to bind to its ligands iC3b, fibrinogen, and
      CD54, and inhibited the ability of human neutrophils to ingest serum opsonized
      particles. NIF thus represents the first example of a disintegrin that targets
      the integrin A-domain, and is likely to be used by the hookworm to evade the
      host's inflammatory response. The unique structure of NIF, which lacks a
      disintegrin motif, emphasizes basic structural differences in antagonists
      targeting A+ and A- integrins, that should be valuable in drug design efforts
      aimed at generating novel therapeutics. Identification of the region in NIF
      mediating A-domain binding should also be useful in this regard, and may, as in
      the case of disintegrins, unravel a new structural motif with cellular
      counterparts mediating important physiologic functions.

PMID- 7528752
TI  - Overcoming obstacles to metastasis--defenses against host defenses: osteopontin
      (OPN) as a shield against attack by cytotoxic host cells.
AB  - Osteopontin (OPN) serves both a cell attachment function and a cell signalling
      function via the alpha v beta 3 integrin. In its cell attachment capacity it can
      promote attachment of both osteoclasts to bone hydroxyapatite and various other
      cell types to basement membrane/extracellular matrix. In its cell signalling
      capacity it initiates a signal transduction cascade that includes changes in the
      intracellular calcium ion levels and the tyrosine phosphorylation status of
      several proteins including paxillin. Effects on gene expression include
      suppression of the induction of nitric oxide synthase by inflammatory mediators.
      OPN can also reduce cell oxidant levels and inhibit the killing of tumor cells by
      activated macrophages and endothelial cells. We hypothesize that those cancer
      cells that produce OPN at elevated levels can suppress the oxidative burst,
      inhibit NO production, and thus protect themselves from killing by specific host
      cell types.

PMID- 7528754
TI  - Are stress and coping associated with WISC-III performance among children?
AB  - This study examined the association between stress/coping variables and the newly
      developed Wechsler Intelligence Scale for Children--III (WISC-III) among
      children. Subjects included 98 children (72 males, 26 females), who ranged in age
      from 6 to 16 years and who were referred for multidisciplinary diagnostic testing
      during 1992-93. Demographic, DSM-III-R diagnostic, and testing data from the WISC
      III were obtained from patient charts. Results suggest that stress and coping are
      associated with WISC-III performance among referred children in this archival and
      correlational study. Implications for future research are discussed.

PMID- 7528753
TI  - Differential effects of retinoic acid and growth factors on osteoblastic markers
      and CD10/NEP activity in stromal-derived osteoblasts.
AB  - The effects of retinoic acid (RA) on the expression of osteoblastic-related cell
      markers was examined. A marrow stromal osteogenic cell line, MBA-15, was analyzed
      by Northern blotting for the expression of bone matrix proteins. These cells
      constitutively express mRNA encoding for procollagen alpha 2 (I), osteonectin,
      osteopontin, biglycan, and alkaline phosphatase (ALK-P). Gene expression was
      unchanged in response to RA triggering for 24 hr. Furthermore, cell growth and
      enzymatic activities of ALK-P and neutral endopeptidase (CD10/NEP) were studied.
      These parameters were examined in MBA-15 and clonal populations representing
      different stages of differentiation. The cell's growth rate was unchanged, while
      ALK-P activity was greatly increased during the culture period under RA treatment
      in MBA-15 and in the clonal cell lines examined while CD10/NEP activity displayed
      a different pattern. MBA-15.4, a preosteoblast cell line, exhibited an inhibition
      in CD10/NEP activity at the beginning of the culture period, reaching basal level
      with time. This activity was greatly increased over control level in MBA-15.6, a
      mature stage of osteoblasts. Furthermore, the response of cell lines to various
      growth factors was tested subsequent to priming the cultures with RA. A
      synergistic effect was monitored for ALK-P activity in MBA-15.4 and MBA-15.6
      cells under rh-bone morphogenic protein (BMP-2) and purified osteogenin (BMP-3),
      and an antagonist effect was measured when cells were exposed to transforming
      growth factor beta (TGF beta). Contrarily, BMP-2 and BMP-3 inhibited the CD10/NEP
      activity that had remained unchanged following priming of the cell with RA.
      Insulin-like growth factor I (IGF-I) and basic fibroblast growth factors (bFGF)
      did not affect either ALK-P nor CD10/NEP activities in both cloned cells.
      Cellular response to bone-seeking hormone, parathyroid hormone (PTH), and
      prostaglandin E2 (PGE2) was monitored by activation of intracellular cAMP.
      Treatment with RA caused a dramatic decrease in MBA-15.6 cell responses to PTH
      and PGE2, but no significant effects could be observed in other clonal lines.

PMID- 7528755
TI  - Risperidone and obsessive-compulsive symptoms.

PMID- 7528756
TI  - Nitrergic innervation of the rat esophagus: focus on motor endplates.
AB  - Nitric oxide synthase immunocytochemistry and correlated NADPH-diaphorase
      histochemistry were utilized to investigate nitrergic innervation of the rat
      esophagus. Almost all neuronal cell bodies and fibers around blood vessels, and
      in submucosa and mucosa which were immunoreactive for NOS, also co-stained for
      NADPH-diaphorase. A combined demonstration of motor endplates with
      tetramethylrhodamine alpha-bungarotoxin or calcitonin gene-related peptide
      immunocytochemistry demonstrated a nitrergic co-innervation of striated muscle
      fibers in all portions of the esophagus. The proportion of endplates co-stained
      increased from 35% to 78% from the cervical to the abdominal portion of the
      esophagus. These data indicate a role for NO in neuromuscular transmission in
      striated muscle of the esophagus.

PMID- 7528757
TI  - Absence of paravascular nerve projection and cross-innervation in interscapular
      brown adipose tissues of mice.
AB  - To determine whether a paravascular nerve projection or cross-innervation exists
      in the interscapular brown adipose tissue (BAT), the distribution of
      noradrenergic or peptidergic nerve fibers in intact or denervated interscapular
      BAT pads of mice was examined histochemically. Noradrenaline (NA) fibers were
      visualized by the glyoxylic acid condensation method, and neuropeptide Y (NPY)
      and substance P (SP) fibers were detected immunohistochemically. Numerous NA
      positive fibers and a few NPY- or SP-positive fibers were observed around
      intralobular arterioles in intact BAT pads. Some NA-positive fibers and very few
      NPY- or SP-positive fibers were seen around interlobular arteries. NA- and NPY
      positive fibers were also found around brown adipose cells in the parenchyme of
      BAT, whereas SP-positive fibers were absent around the cells. However, all
      sections cut from denervated BAT pads of unilaterally or bilaterally denervated
      animals showed a total absence of NA-, NPY- or SP-positive nerve fibers.
      Therefore, neither a paravascular projection of NA, NPY, and SP fibers to the BAT
      nor a cross-innervation of these nerve fibers between the left and right BAT pads
      exists in the mouse BAT.

PMID- 7528758
TI  - Development of hepatocellular carcinoma among patients with chronic liver disease
      due to hepatitis C viral infection.
AB  - Although chronic infection with hepatitis C (HCV) and B viruses (HBV) are
      important risk factors for hepatocellular carcinoma (HCC), their relative roles
      in causing liver cancer remain poorly defined, particularly in developed Western
      countries. Thirty-one patients with HCC seen at the Clinical Center of the
      National Institutes of Health between 1986 and 1992 were evaluated serologically
      for evidence of HBV and HCV infection: antibodies to HBV and HCV and hepatitis B
      surface antigen (HBsAg) were detected by conventional immunoassays, and HCV RNA
      and HBV DNA were detected by polymerase chain reaction (PCR). Serologic evidence
      of HBV infection was found in 18 patients (56%), 17 with antibodies, 16 with HBV
      DNA, and 14 with HBsAg. Evidence of HCV infection was found in 10 patients (32%),
      seven of whom also had HCV RNA. One patient had both anti-HCV and HBsAg. In
      comparison to patients with HBV-related HCC, those with HCV-related cancer were
      older and more likely to be white, to have been born in the United States, to
      have a history of parenteral exposure, and to have cirrhosis. In two patients in
      whom the course of hepatitis C could be traced from its onset, hepatocellular
      carcinoma developed after 5 years in one and after 9 years in another case. Thus
      chronic HCV infection is a common etiology of cirrhosis among United States
      patients with HCC, often as a late complication of intravenous drug abuse or
      blood transfusion.

PMID- 7528759
TI  - Inverse correlation between the titre of antibody to hepatitis C virus and the
      degree of hepatitis C viraemia.
AB  - We titrated 277 hepatitis C virus (HCV) antibody-positive serum samples from 235
      volunteer blood donors as well as from 42 outpatients of a hospital for elderly
      people and studied the relation of the titre of HCV antibody to the presence of
      HCV RNA, of antibody to C100 protein (anti-c100) and of antibody to GOR epitope
      (anti-GOR). Liver dysfunction was measured also. Of 177 HCV RNA-positive serum
      samples, 87 were tested for the degree of HCV viraemia by means of a competitive
      assay. Among the 277 samples, prevalences of HCV RNA, anti-c100, anti-GOR and
      liver dysfunction were 63.9%, 71.8%, 75.7% and 17.5%, respectively. The
      prevalence of HCV RNA became higher as the titre of HCV antibody increased. The
      titre tended to increase with age but the tendency was not statistically
      significant. The mean titre was higher in females (2(10.4 +/- 1.8)) than in males
      (2(9.4 +/- 2.2)) (P < 0.01). In the HCV RNA-positive serum samples, the HCV
      antibody titre was significantly higher in the anti-c100-positive samples than in
      the negative ones. This difference between the positive and negative samples,
      however, was not statistically significant for anti-GOR and liver dysfunction.
      Low degrees of HCV viraemia were accompanied by high titres of HCV antibody while
      high degrees of HCV viraemia went with low titres of HCV antibody. The study
      revealed that titres of HCV antibody were higher in females and the degree of HCV
      viraemia correlated inversely with the titre of HCV antibody.

PMID- 7528760
TI  - The effect of L-buthionine-[S,R]-sulfoximine on the pancreas in mice. A model of
      weakening glutathione-based defense mechanisms.
AB  - L-Buthionine-[S,R]-Sulfoximine (BSO) decreases glutathione levels in various
      organs by inhibition of gamma-glutamylcysteine synthetase. We have examined the
      levels of total glutathione and oxidized glutathione in the pancreas of mice, as
      well as serum amylase and pancreatic histology, after BSO administration in two
      different ways. The injection of a single dose of BSO (5 mmol/kg body wt)
      decreased total glutathione to 10% of the control value. A similar depletion was
      observed after 24 h of oral administration of a 10 mM BSO solution, without
      changes in the levels of oxidized glutathione. BSO-induced pancreatic glutathione
      depletion--even if maintained for up to 14 d--did not cause morphological
      alterations of the pancreas or hyperamylasemia. Thus pancreatic glutathione
      depletion in itself does not lead to pancreatitis, although during development of
      experimental acute pancreatitis, glutathione depletion has been described. BSO
      might be used in animal models to weaken the glutathione-based acinar defense
      mechanisms against oxidant stress or to alter other physiologic processes in
      which glutathione is involved.

PMID- 7528761
TI  - Alterations of pancreatic amylase secretion in the reserpinized rat model of
      cystic fibrosis. Effects of cerulein and EGF.
AB  - Reserpine treatment resulted in altered enzyme secretion from rat pancreatic
      acini in response to carbamylcholine and secretin (1,2). This study was
      undertaken: (1) To evaluate if the alterations caused by reserpine can be
      prevented by EGF and/or cerulein treatments; (2) To determine the time-course of
      secretion recovery after reserpine treatment; and (3) To establish if EGF and/or
      cerulein treatments can accelerate such a recovery after the reserpine treatment.
      Male Sprague-Dawley rats (250-265 g) were used in these experiments. In
      experiment I, rats divided into three groups received either reserpine (R) or the
      reserpine vehicle for the controls (C) and the pair-fed controls (PF) for 7 d.
      During treatment, PF and R rats were given SC, twice a day, saline, EGF (10
      micrograms/kg), cerulein (1 microgram/kg), or both at the same dose. C rats
      received saline in gelatin. In experiment II, rats were treated for 7 d with
      reserpine or the vehicle as described in experiment I, were allowed a 30-d
      recovery period and then were killed. In experiment III, C, PF, and R rats were
      treated for 7 d as described in experiment I; on the 8th d and for the next 6 d,
      reserpine rats received saline (reserpine-saline), cerulein, EGF, or both
      cerulein +EGF at the same dose as indicated in experiment I. C and PF rats
      received saline in gelatin. After sacrifice, acini were prepared, and amylase
      dose-response curves to carbamylcholine (Cch) and secretin were established. EGF,
      cerulein, or their combination given to R rats did not improve the desensitized
      secretory response to Cch.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528762
TI  - Nafamostat mesilate on the course of acute pancreatitis. Protective effect on
      peritoneal permeability and relation with supervening pulmonary distress.
AB  - Three hundred sixty Sprague-Dawley rats were allocated into four groups,
      according to different content of a 24-h i.v. infusion performed 1 h after
      intrabiliary injection of enterokinase/sodium taurocholate to induce acute
      pancreatitis (AP): (1) Saline; (2) 5 micrograms/kg/h nafamostat mesilate (FUT
      175); (3) 10 micrograms/kg/h FUT-175; and (4) 25 micrograms/kg/h FUT-175.
      Peritoneal fluid was removed and exchanged with 1 mL 3.33 M fluorescein
      isothiocyanate-conjugated (FITC) dextrans of 4000-40,000 Dalton. Serial blood
      samples were withdrawn and examined for FITC-dextrans, phospholipase A2 (PLA2),
      blood gases, amylase, and lipase. As compared to control (55%), FUT-175 brought
      about a lower (5 micrograms/kg/h: 25%) or no mortality (10 and 25
      micrograms/kg/h), and a milder histological and biochemical evidence of AP.
      Untreated animals with PLA2 values over two times the standard deviation showed a
      respiratory distress. Further, unlike group 1, FUT-175 doses as low as 5
      micrograms/kg prevented the increase in peritoneal permeability to small-size
      molecules (up to 20,000 Dalton). In a second experiment under the same drug
      protocol, 1000 U/mL of PLA2 and 2 mL of pancreatitis ascites were instilled ip.
      Peritoneal permeability to FITC-dextrans up to 30,000 Dalton and to PLA2
      significantly increased in the saline group and in the 5 micrograms/kg FUT-175
      group. However, 10 micrograms/kg and 25 micrograms/kg FUT-175 doses prevented
      such phenomenon. In conclusion, FUT-175 proves to be a potent antiprotease
      molecule with a biochemical activity also against PLA2 in vivo and prevents
      significant transperitoneal-blood access of pancreatic enzymes.

PMID- 7528763
TI  - Apoptosis defects analyzed in TcR transgenic and fas transgenic lpr mice.
AB  - Although autoreactive T cells are thought to play a prominent role in autoimmune
      disease in MRL-lpr/lpr mice, it has been difficult to directly determine if
      autoreactive T cells escape from the thymus and react with self-antigens in the
      periphery. Defective expression of the Fas apoptosis antigen in MRL-lpr/lpr mice
      results from the insertion of the ETn retrotransposon. The fas defect can be
      partially corrected in CD2-fas transgenic mice in which the expression of fas is
      corrected in T cells. To identify a possible defect in clonal deletion or clonal
      anergy induction of auto-specific T cells, we have studied C57BL/6-lpr/lpr
      transgenic mice that express TcR genes that recognize a known self-antigen, the
      male H-Y antigen. In addition, we have analyzed clonal deletion and tolerance
      induction after neonatal tolerance induction and superantigen-induced arthritis
      with the class II MHC reactive superantigen staphylococcal enterotoxin B (SEB) in
      V beta 8 TcR transgenic and non-transgenic MRL-lpr/lpr mice. Neonatal tolerance
      induction to SEB was normal in lpr/lpr mice. However, over time a loss of
      tolerance (thymic or peripheral) was observed in lpr/lpr mice but not in +/+ TcR
      transgenic mice. This defect in lpr/lpr mice was thymic-dependent and was due to
      increased CD28/CTLA4 signaling. These results suggest that an apoptosis defect
      involving both thymocytes and peripheral lymphoid cells leads to autoimmune
      disease in lpr/lpr mice. The challenge in the future will be to determine the
      role of defective apoptosis in other autoimmune diseases.

PMID- 7528764
TI  - Establishment of enzyme-linked immunosorbent assays for lipoprotein lipase with
      newly developed antibodies.
AB  - We developed eight new antibodies against lipoprotein lipase (LPL), which
      included polyclonal antibodies raised against recombinant human LPL produced by
      transformant cells and two synthetic peptides corresponding to either amino (N)-
      or carboxy (C)-terminus of human LPL. With these antibodies, we established three
      effective sandwich enzyme-linked immunosorbent assays (ELISAs) for LPL, which
      enabled us to examine LPL mass not only in the postheparin plasma from human,
      rat, mouse, and guinea pig but also in the media and lysates of cultured cells.
      All of the developed antibodies showed high affinities for LPL, but their binding
      to LPL did not always influence the lipolytic activity of the enzyme.
      Interestingly, although the anti-C-terminus antibody should bind to a common
      epitope of human and mouse LPL, its binding selectively suppressed only human LPL
      activity. Because amino acid sequence surrounding the epitope is common to both
      LPLs, difference in the sequence outside the epitope will contribute to the
      selective suppression of LPL activity by the antibody. Our results also suggested
      that both termini of LPL would be exposed on the surface of the molecule because
      they were fully accessible to antibodies and that the N-terminus of LPL would be
      functionally less important because binding of the anti-N-terminus antibody did
      not affect human LPL activity. The ELISAs were further utilized to demonstrate
      the presence of C-terminus truncated LPL protein in the postheparin plasma of an
      LPL-deficient patient, to map an epitope of the anti-C-terminus antibody within
      residues 433-436, and to gain insight into the structure-function relationship of
      the LPL molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528765
TI  - Dual binding capacity of mucosal immunoblasts to mucosal and synovial endothelium
      in humans: dissection of the molecular mechanisms.
AB  - Lymphocytes continuously migrate throughout the body in search of antigens.
      Virgin lymphocytes recirculate freely between the blood and different lymphatic
      organs, whereas immunoblasts extravasate preferentially into sites similar to
      those where they initially responded to antigen. Tissue-specific extravasation of
      lymphocytes is largely controlled by distinct lymphocyte surface receptors that
      mediate lymphocyte binding to high endothelial venules (HEV). In the present
      study, the molecular mechanisms determining the specificity of human mucosal
      (lamina propria) lymphocyte binding to different endothelial recognition systems
      were analyzed. Mucosal immunoblasts adhered five times better than small mucosal
      lymphocytes to mucosal HEV. Importantly, mucosal immunoblasts also bound to
      synovial HEV almost as efficiently as to mucosal HEV, but they did not adhere to
      peripheral lymph node HEV. To study the impact of different homing-associated
      molecules in this dual endothelial binding, we used a gut-derived T cell line and
      freshly isolated mucosal immunoblasts. Both cell types expressed integrins alpha
      4, beta 1, beta 7, and lymphocyte function associated antigen 1 (LFA-1), and were
      CD44 positive, but practically L-selectin negative. Binding of mucosal
      immunoblasts to mucosal HEV was almost completely abolished by pretreatment with
      anti-beta 7 monoclonal antibodies, but it was independent of alpha 4/beta 1
      function. In contrast, alpha 4/beta 1 partially mediated immunoblast adherence to
      synovial HEV, whereas alpha 4/beta 7 had only a minor role in adherence of blasts
      at this site. CD44 and LFA-1 contributed to HEV-binding both in mucosa and
      synovium. Taken together, this is the first report that demonstrates a critical
      role for alpha 4/beta 7 in the binding of gut lymphocytes to mucosal venules in
      humans. Moreover, a hitherto unknown interaction between mucosal effector cells
      and synovial endothelial cells was shown to be only partially mediated by the
      currently known homing receptors. The dual endothelial binding capacity of
      mucosal blasts may help to explain the pathogenesis of reactive arthritis not
      uncommonly associated with inflammatory and infectious bowel disease.

PMID- 7528766
TI  - Mouse complement regulatory protein Crry/p65 uses the specific mechanisms of both
      human decay-accelerating factor and membrane cofactor protein.
AB  - Normal host cells are protected from the destructive action of complement by cell
      surface complement regulatory proteins. In humans, decay-accelerating factor
      (DAF) and membrane cofactor protein (MCP) play such a biologic role by inhibiting
      C3 and C5 convertases. DAF and MCP accomplish this task by specific mechanisms
      designated decay-accelerating activity and factor I cofactor activity,
      respectively. In other species, including mice, structural and/or functional
      homologues of these proteins are not yet well characterized. Previous studies
      have shown that the mouse protein Crry/p65 has certain characteristics of self
      protecting complement regulatory proteins. For example, Crry/p65 is expressed on
      a wide variety of murine cells, and when expressed on human K562 erythroleukemic
      cells, it prevents deposition of mouse C3 fragments on the cell surface during
      activation of either the classical or alternative complement pathway. We have now
      studied factor I cofactor and decay-accelerating activities of Crry/p65.
      Recombinant Crry/p65 demonstrates cofactor activity for factor I-mediated
      cleavage of both mouse C3b and C4b. Surprisingly, Crry/p65 also exhibits decay
      accelerating activity for the classical pathway C3 convertase strongly and for
      the alternative pathway C3 convertase weakly. Therefore, mouse Crry/p65 uses the
      specific mechanisms of both human MCP and DAF. Although Crry/p65, like MCP and
      DAF, contains tandem short consensus repeats (SCR) characteristic of C3/C4
      binding proteins, Crry/p65 is not considered to be a genetic homologue of either
      MCP or DAF. Thus, Crry/p65 is an example of evolutionary conservation of two
      specific activities in a single unique protein in one species that are dispersed
      to individual proteins in another. We propose that the repeating SCR motif in
      this family has allowed this unusual process of evolution to occur, perhaps
      driven by the use of MCP and DAF as receptors by human pathogens such as the
      measles virus.

PMID- 7528767
TI  - Early molecular events induced by T cell receptor (TCR) signaling in immature
      CD4+ CD8+ thymocytes: increased synthesis of TCR-alpha protein is an early
      response to TCR signaling that compensates for TCR-alpha instability, improves
      TCR assembly, and parallels other indicators of positive selection.
AB  - Differentiation of immature CD4+ CD8+ thymocytes into mature CD4+ or CD8+ T cells
      occurs within the thymus and is dependent upon expression of antigen receptor
      complexes (T cell receptor [TCR]) containing clonotypic alpha/beta proteins. We
      have recently found that CD4+ CD8+ thymocytes express low levels of surface TCR
      because of limitations placed on TCR assembly by the instability of nascent TCR
      alpha proteins within the endoplasmic reticulum (ER) of immature thymocytes.
      Because TCR-alpha/beta expression increases during development, a molecular
      mechanism must exist for increasing the number of assembled TCR complexes present
      in immature CD4+ CD8+ thymocytes that have been signaled to differentiate into
      mature T cells, although no such mechanism has yet been described. In the current
      report we have examined the molecular consequences of intracellular signals
      generated by engagement of surface TCR complexes on immature CD4+ CD8+
      thymocytes. Isolated TCR engagement generated signals that increased TCR-alpha
      RNA levels and increased synthesis of TCR-alpha proteins, which, in turn,
      significantly increased assembly of complete TCR-alpha/beta complexes in CD4+
      CD8+ thymocytes. Increased TCR-alpha protein levels in TCR-signaled CD4+ CD8+
      thymocytes was the result of increased synthesis and not increased stability of
      TCR-alpha proteins, indicating that TCR engagement compensates for, but does not
      correct, the inherent instability of TCR-alpha proteins in the ER of immature
      thymocytes. Consistent with the delivery by TCR engagement of a positive
      selection signal, TCR engagement also increased CD5 expression, decreased RAG-1
      expression, and decreased CD4/CD8 coreceptor expression in immature CD4+ CD8+
      thymocytes. These data identify amplified TCR-alpha expression as an initial
      response of immature CD4+ CD8+ thymocytes to TCR-mediated positive selection
      signals and provide a molecular basis for increased surface TCR density on
      developing thymocytes undergoing selection events within the thymus.

PMID- 7528768
TI  - Presentation by a major histocompatibility complex class I molecule of
      nucleoprotein peptide expressed in two different genes of an influenza virus
      transfectant.
AB  - Major histocompatibility (MHC) class I glycoproteins are specialized to present
      to CD8+ T cells, peptides that originate from proteins synthesized within the
      cytoplasm. Conventional killed vaccines are unable to get into the cell cytoplasm
      and therefore fail to expand the CD8+ T cell population. We have created a novel
      influenza transfectant virus, R10, which carries an immunogenic peptide from the
      nucleoprotein (NP) of PR8 influenza virus in its hemagglutinin (HA) and another
      similar peptide in its HK influenza virus NP. The two peptides are both presented
      by H-2Db and bind with approximately equal affinity. They can compete with one
      another for binding to H-2Db. Yet in cells infected with R10, both peptides are
      presented efficiently enough to expand the respective cytotoxic T lymphocyte
      (CTL) precursors in vivo and to serve as targets for CTL lysis in vitro. It has
      been proposed that proteins bearing signal sequences may be processed by a
      transporter-independent pathway. To investigate this, we infected the transporter
      deficient cell line RMA-S with the R10 virus to see if the NP peptide expressed
      by the HA would be presented. The result shows that even the presence of a signal
      peptide in the HA does not overcome the lack of a transporter function,
      suggesting that the presentation of both peptides is dependent on functional
      transporter proteins. Our data also suggest the feasibility of creating by
      genetic engineering, recombinant vaccines expressing multiple epitopes that can
      effectively stimulate a cellular immune response.

PMID- 7528769
TI  - The majority of postselection CD4+ single-positive thymocytes requires the thymus
      to produce long-lived, functional T cells.
AB  - We have previously isolated, and characterized in vitro, two subsets of CD4hi T
      cell receptor (TCR)hi single positive (SP) thymocytes: CD8- and CD8lo. In this
      report, we have analyzed phenotypic, functional, and developmental
      characteristics of these "late" CD4hi SP thymocyte subsets. The TCRhi phenotype
      and the elimination of T cells expressing TCR V beta segments reactive with
      endogenous mouse mammary tumor virus (MMTV) products suggested that both subsets
      had undergone positive and negative selection. CD8-4hi thymocytes were
      functional, as judged by their ability to: (a) induce lethal graft versus host
      disease (GVHD); (b) survive and expand in peripheral lymphoid organs; and (c)
      proliferate, rather than undergo apoptosis, in response to in vitro TCR cross
      linking. By contrast, CD8lo4hi cells could not induce GVHD, were unable to expand
      (and perhaps even survive) in peripheral organs and underwent apoptosis upon TCR
      cross-linking. However, when reintroduced into the thymus, these cells matured
      into functional, long-lived CD8-4hi lymphocytes. These results document an
      obligatory requirement for the thymic microenvironment in the final maturation of
      the majority of CD4hi SP postselection thymocytes, and demonstrate the existence
      of a previously unrecognized control point in T cell development.

PMID- 7528770
TI  - Different roles for the Fc epsilon RI gamma chain as a function of the receptor
      context.
AB  - The high affinity immunoglobulin E receptor (Fc epsilon RI) and the B and T cell
      antigen receptors (TCR) are multimeric complexes containing subunits with
      cytoplasmic antigen recognition activation motifs (ARAMs). The presence of
      multiple motifs may be a way to amplify a single signal or provide independent
      activation modules. Here we have compared the signaling capacity of the same Fc
      epsilon RI gamma motif in the context of two different receptors, Fc epsilon RI
      and TCR/CD3, simultaneously reconstituted on the surface of the same zeta
      deficient T cell line. Both reconstituted receptors mediate early
      (phosphorylation) and late (interleukin [IL]-2 release) signals. Mutation of the
      two tyrosine residues of ARAM gamma alters early signaling by both receptors, but
      the set of substrates phosphorylated via ARAM gamma is different for each
      receptor and is thus dependent on the receptor context. Furthermore, the
      mutations prevent Fc epsilon RI- but not TCR/CD3-mediated IL-2 release. These
      data demonstrate that ARAM gamma is necessary for allowing both receptors to
      phosphorylate the complete set of substrates, and that the CD3 complex, unlike
      the Fc epsilon RI beta chain, contains activation modules capable of compensating
      for the absence of a functional ARAM gamma in generating late signals such as IL
      2 release.

PMID- 7528771
TI  - Receptor-induced death in human natural killer cells: involvement of CD16.
AB  - Propriocidal regulation of T cells refers to apoptosis induced by interleukin 2
      (IL-2) activation with subsequent antigen receptor stimulation. We examined
      whether natural killer (NK) cells exhibited cytokine- and ligand-induced death
      similar to activated T cells. Peripheral NK cells were examined for ligand
      induced death using antibodies to surface moieties (CD2, CD3, CD8, CD16, CD56),
      with and without prior activation of IL-2. Only those NK cells stimulated first
      with IL-2 and then with CD16 exhibited ligand-induced death; none of the other
      antibody stimuli induced this phenomenon. Next we examined various cytokines (IL
      2, IL-4, IL-6, IL-7, IL-12, IL-13, interferon alpha and gamma) that can activate
      NK cells and determined if CD16-induced killing occurred. Only IL-2 and IL-12
      induced NK cell death after occupancy of this receptor by aggregated
      immunoglobulin or by cross-linking with antireceptor antibody. The CD16-induced
      death was inhibited by herbimycin A, indicating that cell death was dependent
      upon protein tyrosine kinases. Identical to T cells, the form of cell death for
      NK cells was demonstrated to be receptor-induced apoptosis. Overall these data
      indicate that highly activated NK cells mediate ligand-induced apoptosis via
      signaling molecules like CD16. Whereas the propriocidal regulation of T cells is
      antigen specific, this is not the case for NK cells due to the nature of the
      receptor. The clinical implications of this finding are considered.

PMID- 7528772
TI  - ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs:
      the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs
      with varying affinity.
AB  - Engagement of the T cell antigen receptor (TCR) results in activation of several
      tyrosine kinases leading to tyrosine phosphorylation of protein substrates and
      activation of multiple biochemical pathways. TCR-mediated activation of the src
      family kinases, Lck and Fyn, results in tyrosine phosphorylation of the TCR zeta
      and CD3 chains. The site of phosphorylation in these chains is the tyrosine-based
      activation motif (TAM), a 15-16 amino acid module containing two tyrosine
      residues. Tyrosine-phosphorylated TAMs serve as targets for binding of the zeta
      associated protein (ZAP-70) tyrosine kinase via its tandem SH2 domains. This
      binding correlates with activation of ZAP-70, a critical event in T cell
      activation. To further define the structural requirements for ZAP-70 interaction
      with the TCR, we developed a binding assay using immobilized glutathione S
      transferase fusion proteins containing the NH2- and/or COOH-terminal SH2 domains
      of ZAP-70, and soluble synthetic peptides with the sequence of the cytoplasmic
      region of the TCR zeta chain (TCR zeta cyt) or individual TCR zeta and CD3
      epsilon TAM motifs. Direct binding studies demonstrated that the tandem ZAP-70
      SH2 domains bind phosphorylated, but not nonphosphorylated, TCR zeta cyt. The NH2
      terminal ZAP-70 SH2 domain also binds to TCR zeta cyt but with 100-fold lower
      affinity. No binding was observed with the COOH-terminal ZAP-70 SH2 domain.
      Similar studies demonstrated that the ZAP-70 tandem SH2 domain can bind a TCR
      zeta 3 TAM peptide in which both tyrosine residues are phosphorylated: Little or
      no binding was observed with peptides phosphorylated at only one tyrosine
      residue, or a nonphosphorylated peptide. Binding of the tandem SH2 domains to the
      other two TCR zeta TAM peptides and to a CD3 epsilon TAM peptide was also
      observed. All four doubly tyrosine phosphorylated TAM peptides cross-compete with
      each other for binding to the tandem SH2 domains of ZAP-70. The affinity of these
      peptides for the tandem SH2 construct demonstrated a hierarchy of TAM zeta 1 > or
      = TAM zeta 2 > TAM epsilon > or = TAM zeta 3. The results provide further
      evidence that the ZAP-70 interaction with the TCR requires prior phosphorylation
      of both tyrosine residues within a TAM motif. Binding of ZAP-70 to phospho-TAMs
      is notable for the high level of cooperativity between the two SH2 domains, which
      individually demonstrate low affinity interaction with the ligand. The
      cooperativity ensures higher affinity for the doubly phosphorylated ligand.
      Affinity differences of as much as 30-fold indicates a significant specificity of
      interaction of ZAP-70 SH2 domains for different phospho-TAMs.

PMID- 7528773
TI  - Prevention of experimental autoimmune encephalomyelitis by antibodies against
      interleukin 12.
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the
      central nervous system that can be transferred to naive mice via CD4+ T cells
      isolated from appropriately immunized mice. We have evaluated the effects of
      recombinant murine interleukin 12 (rmIL-12), a potent inducer of interferon gamma
      (IFN-gamma) and promoter of Th1 T cell development, on the course of adoptively
      transferred EAE. The transfer of lymph node cells (LNC) isolated from proteolipid
      protein (PLP)-primed animals and stimulated in vitro with PLP to naive mice
      resulted in a progressive paralytic disease culminating in complete hind limb
      paralysis in the majority of the recipients. When mice were injected with LNC
      that had been stimulated in vitro with PLP in the presence of rmIL-12, the
      subsequent course of disease was more severe and prolonged. The addition of rmIL
      12 during the in vitro stimulation with PLP resulted in a 10-fold increase in IFN
      gamma and a 2-fold increase in tumor necrosis factor (TNF) alpha in the
      supernatants, relative to LNC stimulated with PLP alone. However, neutralization
      of IFN-gamma or TNF-alpha in vitro with specific antibodies did not abrogate the
      ability of rmIL-12 to exacerbate the subsequent disease. Similarly, mice treated
      with rmIL-12 in vivo after the transfer of antigen-stimulated LNC developed a
      more severe and prolonged course of disease compared with vehicle-treated control
      animals. In contrast, treatment of mice with an antibody to murine IL-12 after
      cell transfer completely prevented paralysis, with only 40% of the mice
      developing mild disease. These results demonstrate that in vitro stimulation of
      antigen primed LNC with PLP and rmIL-12 enhances their subsequent
      encephalitogenicity. Furthermore, inhibition of endogenous IL-12 in vivo after
      LNC transfer prevented paralysis, suggesting that endogenous IL-12 plays a
      pivotal role in the pathogenesis of this model of autoimmune disease.

PMID- 7528774
TI  - Massive upregulation of the Fas ligand in lpr and gld mice: implications for Fas
      regulation and the graft-versus-host disease-like wasting syndrome.
AB  - Fas-deficient lpr and gld mice develop lymphadenopathy due to the accumulation of
      T cells with an unusual double negative (DN) (CD4-CD8-) phenotype. Previous
      studies have shown that these abnormal cells are capable of inducing redirected
      lysis of certain Fc receptor-positive target cells. Since the Fas ligand (FasL)
      has recently been shown to be partly responsible for T cell-mediated
      cytotoxicity, lymph node cells from lpr and gld mice were examined for the
      expression of FasL mRNA. Northern blot analysis revealed that lymph node cells
      obtained from lpr and gld mice had a striking increase in the level of expression
      of FasL mRNA predominantly due to expression in the DN T cells. Furthermore, lpr,
      but not gld lymph node cells killed the B cell line, A20, in a Fas-dependent
      manner. These findings indicate that Fas mutations result in a massive up
      regulation of FasL which, most likely, results from repetitive exposure to (self)
      antigen. This phenomenon could explain the lpr-induced wasting syndrome observed
      when lpr bone marrow-derived cells are adoptively transferred to wild-type
      recipients.

PMID- 7528776
TI  - Very late activation antigen 4-vascular cell adhesion molecule 1 interaction is
      involved in the formation of erythroblastic islands.
AB  - Erythroblastic islands are anatomical units consisting of a central macrophage
      surrounded by erythroblasts. We studied the adhesion molecules involved in the
      formation of these structures. Central macrophages of erythroblastic islands
      isolated from the spleens of phlebotomized mice were clearly stained for vascular
      cell adhesion molecule 1 (VCAM-1). The surrounding erythroblasts of the
      erythroblastic islands strongly expressed the alpha 4 integrin of very late
      activation antigen 4 (VLA-4: alpha 4 beta 1 integrin), the counter receptor of
      VCAM-1, whereas most reticulocytes and erythrocytes did not. Both monoclonal
      antibodies (mAbs) against alpha 4 integrin and VCAM-1 disrupted the
      erythroblastic islands cultured in the presence of erythropoietin. Moreover,
      adhesion of splenic erythroblasts to tumor necrosis factor alpha-stimulated mouse
      splenic endothelial cells, which showed high expression of VCAM-1 but not
      intercellular adhesion molecule 1, was inhibited by the anti-VCAM-1 and anti
      alpha 4 mAbs. These findings suggest that VLA-4-VCAM-1 interaction plays a
      crucial role in the formation of erythroblastic islands.

PMID- 7528775
TI  - Interleukin 12 (IL-12) induces tyrosine phosphorylation of JAK2 and TYK2:
      differential use of Janus family tyrosine kinases by IL-2 and IL-12.
AB  - Interleukin (IL-12) has many effects on the function of natural killer and T
      cells, and is important in the control of cell-mediated immunity. IL-2 and IL-12
      display many similar activities, yet each also induces a distinct set of
      responses. A human IL-12 receptor subunit has recently been cloned and, like the
      IL-2R beta and IL-2R gamma, is a member of the hematopoietic receptor
      superfamily; however, the molecular mechanisms of IL-12 action are unknown. In
      this report we show that IL-12 and IL-2 induce tyrosine phosphorylation of
      distinct members of the Janus (JAK) family of protein tyrosine kinases in human T
      lymphocytes. IL-12, but not IL-2, stimulates the tyrosine phosphorylation of TYK2
      and JAK2, whereas JAK1 and JAK3, which are phosphorylated in response to IL-2,
      are not phosphorylated after IL-12 treatment. The use of distinct but related JAK
      family tyrosine kinases by IL-12 and IL-2 may provide a biochemical basis for
      their different biological activities.

PMID- 7528777
TI  - Amino acid residues required for binding of lymphocyte function-associated
      antigen 3 (CD58) to its counter-receptor CD2.
AB  - Efficient activation and regulation of the cellular immune response requires
      engagement of T cell accessory molecules as well as the antigen-specific T cell
      receptor. The lymphocyte function-associated antigen (LFA) 3 (CD58)/CD2 accessory
      pathway, one of the first discovered, has been extensively characterized in terms
      of structure and function of the CD2 molecule, which is present on all T
      lymphocytes and natural killer cells of the human immune system. The binding site
      of human CD2 for LFA-3 has been localized to two epitopes on one face of the
      first immunoglobulin (Ig)-like domain of this two-domain, Ig superfamily
      molecule. Human LFA-3 is genetically linked and is 21% identical in amino acid
      sequence to CD2, suggesting that this adhesive pair may have evolved from a
      single ancestral molecule. We have aligned the amino acid sequences of LFA-3 and
      CD2 and mutagenized selected amino acids in the first domain of LFA-3 that are
      analogous to those implicated in the binding site of CD2. The data show that K30
      and K34, in the predicted C-C' loop, and D84, in the predicted F-G loop of LFA-3,
      are involved in binding to CD2, suggesting that two complementary sites on one
      face of the first domain of each molecule bind to each other.

PMID- 7528778
TI  - Defective phosphorylation and hyaluronate binding of CD44 with point mutations in
      the cytoplasmic domain.
AB  - CD44 is a cell surface adhesion molecule that plays a role in leukocyte
      extravasation, leukopoiesis, T lymphocyte activation, and tumor metastasis. The
      principal known ligand for CD44 is the glycosaminoglycan hyaluronate, (HA), a
      major constituent of extracellular matrices. CD44 expression is required but is
      not sufficient to confer cellular adhesion to HA, suggesting that the adhesion
      function of the receptor is regulated. We recently demonstrated that CD44 in
      primary leukocytes is phosphorylated in a cell type- and activation state
      dependent fashion. In this study we demonstrate that serines 325 and 327 within
      the cytoplasmic domain of CD44 are required for the constitutive phosphorylation
      of CD44 in T cells. Furthermore, we demonstrate that cells expressing mutated
      CD44 containing a serine to glycine substitution at position 325 or a serine to
      alanine substitution at amino acid 327 are defective in HA binding, CD44-mediated
      adhesion of T cells to smooth muscle cells, as well as ligand-induced receptor
      modulation. The effect of these mutations can be partially reversed by a
      monoclonal anti-CD44 antibody that enhances CD44-mediated HA binding.

PMID- 7528779
TI  - Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide
      synthase.
AB  - The role of nitric oxide in the immune response to allogeneic tissue was explored
      in an in vivo cardiac transplant model in the rat. Nitric oxide production during
      organ rejection was demonstrated by elevations in systemic serum nitrite/nitrate
      levels and by electron paramagnetic resonance spectroscopy. Messenger RNA for the
      inducible nitric oxide synthase enzyme was detected in the rejecting allografted
      heart, but not in the nonrejecting isografted heart. The enzyme was demonstrated
      to be biologically active by the in vitro conversion of L-arginine to L
      citrulline and was immunohistochemically localized to the infiltrating
      inflammatory cells. Treatment with aminoguanidine, a preferential inhibitor of
      the inducible nitric oxide synthase isoform, prevented the increased nitric oxide
      production in the transplanted organ and significantly attenuated the
      pathogenesis of acute rejection. Aminoguanidine treatment prolonged graft
      survival, improved graft contractile function, and significantly reduced the
      histologic grade of rejection. These results suggest an important role for nitric
      oxide in mediating the immune response to allogeneic tissue. Inhibition of
      inducible nitric oxide synthase may provide a novel therapeutic modality in the
      management of acute transplant rejection and of other immune-mediated processes.

PMID- 7528780
TI  - Fas ligand mediates activation-induced cell death in human T lymphocytes.
AB  - A significant proportion of previously activated human T cells undergo apoptosis
      when triggered through the CD3/T cell receptor complex, a process termed
      activation-induced cell death (AICD). Ligation of Fas on activated T cells by
      either Fas antibodies or recombinant human Fas-ligand (Fas-L) also results in
      cytolysis. We demonstrate that these two pathways of apoptosis are causally
      related. Stimulation of previously activated T cells resulted in the expression
      of Fas-L mRNA and lysis of Fas-positive target cells. Fas-L antagonists inhibited
      AICD of T cell clones and staphylococcus enterotoxin B (SEB)-specific T cell
      lines. The data indicate AICD in previously stimulated T cells is mediated by
      Fas/Fas-L interactions.

PMID- 7528781
TI  - Middle T antigen-transformed endothelial cells exhibit an increased activity of
      nitric oxide synthase.
AB  - Endothelioma cell lines transformed by polyoma virus middle T antigen (mTa) cause
      cavernous hemangiomas in syngeneic mice by recruitment of host cells. The
      production of nitric oxide (NO), as measured by nitrite and citrulline
      production, was significantly higher in mTa-transformed endothelial cells in
      comparison with nontransformed control cells. The maximal activity of NO synthase
      (NOS) was about 200-fold higher in cell lysates from the tEnd.1 endothelioma cell
      line than in lysates from nontransformed controls, whereas the affinity for
      arginine did not differ. The biochemical characterization of NOS and the study of
      mRNA transcripts indicate that tEnd.1 cells express both the inducible and the
      constitutive isoforms. NOS hyperactivity is not a simple consequence of cell
      transformation but needs a tissue-specific mTa expression. Since tEnd.1
      conditioned medium induces NOS activity in normal endothelial cells, most likely
      NOS hyperactivity in endothelioma cells is attributable to the release of a
      soluble factor. This NOS-activating factor, which seems to be an anionic protein,
      could stimulate tEnd.1 cells to express NOS by an autocrine way. By the same
      mechanism, tEnd.1 cells could induce NOS in the neighboring endothelial cells,
      and NO release could play a role in the hemangioma development. Such hypothesis
      is confirmed by our in vivo experiments, showing that the administration of the
      NOS inhibitor L-canavanine to endothelioma-bearing mice significantly reduced
      both the volume and the relapse time of the tumor.

PMID- 7528782
TI  - A damped oscillation in the intramembranous charge movement and calcium release
      flux of frog skeletal muscle fibers.
AB  - Asymmetric membrane currents and calcium transients were recorded simultaneously
      from cut segments of frog skeletal muscle fibers voltage clamped in a double
      Vaseline-gap chamber in the presence of high concentration of EGTA
      intracellularly. An inward phase of asymmetric currents following the hump
      component was observed in all fibers during the depolarization pulse to selected
      voltages (congruent to -45 mV). The average value of the peak inward current was
      0.1 A/F (SEM = 0.01, n = 18), and the time at which it occurred was 34 ms (SEM =
      1.8, n = 18). A second delayed outward phase of asymmetric current was observed
      after the inward phase, in those experiments in which hump component and inward
      phase were large. It peaked at more variable time (between 60 and 130 ms) with
      amplitude 0.02 A/F (SEM = 0.003, n = 11). The transmembrane voltage during a
      pulse, measured with a glass microelectrode, reached its steady value in less
      than 10 ms and showed no oscillations. The potential was steady at the time when
      the delayed component of asymmetric current occurred. ON and OFF charge transfers
      were equal for all pulse durations. The inward phase moved 1.4 nC/microF charge
      (SEM = 0.8, n = 6), or about one third of the final value of charge mobilized by
      these small pulses, and the second outward phase moved 0.7 nC/microF (SEM = 0.8,
      n = 6), bringing back about half of the charge moved during the inward phase.
      When repolarization intersected the peak of the inward phase, the OFF charge
      transfer was independent of the repolarization voltage in the range -60 to -90
      mV. When both pre- and post-pulse voltages were changed between -120 mV and -60
      mV, the equality of ON and OFF transfers of charge persisted, although they
      changed from 113 to 81% of their value at -90 mV. The three delayed phases in
      asymmetric current were also observed in experiments in which the extracellular
      solution contained Cd2+, La3+ and no Ca2+. Large increases in intracellular [Cl-]
      were imposed, and had no major effect on the delayed components of the asymmetric
      current. The Ca2+ transients measured optically and the calculated Ca2+ release
      fluxes had three phases whenever a visible outward phase followed the inward
      phase in the asymmetric current. Several interventions intended to interfere with
      Ca release, reduced or eliminated the three delayed phases of the asymmetric
      current.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7528784
TI  - Identification of damaged adult female specimens of Aedes albopictus and Aedes
      aegypti in the New World.
AB  - Two introduced species of Aedes (Stegomyia), Aedes albopictus and Aedes aegypti,
      occur in the New World. Three characters, easily and simultaneously observed from
      an anteroventral view, allow for rapid and reliable specific identification of
      most specimens that lack the characteristic scutal scale patterns. These 3
      characters are the presence or absence of pale scales on the clypeus; the
      presence or absence of a narrow, median line of pale scales on the anterior face
      of the midfemora; and the pattern of pale and dark scales on abdominal sterna III
      V.

PMID- 7528783
TI  - CFTR displays voltage dependence and two gating modes during stimulation.
AB  - The patch-clamp technique in conjunction with current noise analysis was employed
      to clarify the events underlying the regulation of the CFTR (cystic fibrosis
      transmembrane conductance regulator) during cAMP-dependent stimulation. 3T3
      fibroblast cells expressing the CFTR were stimulated in cell-attached mode with
      forskolin. The number (N) of activated channels per patch ranged from 1 to
      approximately 100. In true single-channel recordings, CFTR's gating was best
      described by two open states (approximately 5 and approximately 100 ms) and three
      closed states (< or = 5, approximately 100, and approximately 1,000 ms). Current
      noise analysis resulted in spectra containing two distinct Lorentzian noise
      components with corner frequencies of 1.3 Hz and approximately 50 Hz,
      respectively. Single-channel time constants were dependent on voltage. The
      fastest closed state increased its contribution from 48% at +100 mV to 87% at 
      100 mV, and the medium open state reduced its length to one half, resulting in
      gating dominated by fast events. Similarly, the fast Lorentzian increased its
      amplitude, and its corner frequency increased from 44 Hz at +100 mV to 91 Hz at 
      100 mV, while the slow Lorentzian was voltage independent. In multi-channel
      recordings N.Po (i.e., N times open probability) increased significantly, on
      average by 52% between -90 and +90 mV. Stimulation with forskolin increased Po of
      CFTR to approximately 0.5, which resulted from a decrease of the longest closed
      state while the faster open and closed states were unaffected. Neither corner
      frequency was affected during stimulation. Recordings from multichannel patches
      revealed in addition, unique, very long channel openings (high Po mode, average
      13 s). Channels exhibiting high Po (i.e., Po approximately 1.0) or low Po (i.e.,
      Po approximately 0.5) gating modes were both present in multichannel recordings,
      and CFTRs switched modes during stimulation. In addition, the switch to the high
      Po mode appeared to be a cooperative event for channel pairs. High forskolin
      concentration (i.e., 10 microM) favored transition into the high Po mode,
      suggesting a cellularly mediated regulation of model switching due to a
      fundamental change in configuration of the CFTR. Thus, during stimulation the
      CFTR increased its activity through two distinct effects: the reduction of the
      long closed state and modal switching to the high Po mode.

PMID- 7528785
TI  - Cytotoxic diterpenoids from Isodon megathyrsus.
AB  - A new diterpenoid, megathyrin A, together with three known compounds,
      rabdocoetsins B, C, and D, were isolated from the leaves of Isodon megathyrsus,
      and their structures and nmr spectral data were assigned by a combination of one-
      and two-dimensional nmr techniques. These compounds displayed significant
      cytotoxic activity.

PMID- 7528787
TI  - Fasciculins, enzyme site-directed polypeptides, as motor neurone research tools.
AB  - In order to examine the ability of motor neurones to take up fasciculin (FAS) and
      transport it centrally from muscle terminals to the spinal cord, we injected pure
      FAS 2, a powerful acetylcholinesterase (AChE) inhibitor, into mouse gastrocnemius
      muscle. 21 h later, histochemistry and biochemistry of spinal cord AChE showed an
      almost complete inhibition of motoneuronal AChE, limited to the spinal cord
      segmental levels corresponding to the injected muscle. Axon transport of FAS can
      be exploited to direct peripherally-injected FAS to neurones located in the
      central nervous system (CNS).

PMID- 7528786
TI  - Thalifaberidine, a cytotoxic aporphine-benzylisoquinoline alkaloid from
      Thalictrum faberi.
AB  - From Thalictrum faberi, thalifaberidine [1], a new aporphine-benzylisoquinoline
      alkaloid, together with four known alkaloids, thalifaramine [2], thalifaricine
      [3], thalifarazine [4], and thalifaronine [5], were isolated. Thalifaberidine [1]
      was identified as 6',8-desmethylthalifaberine, and its 1H- and 13C-nmr data were
      completely assigned through the use of one- and two-dimensional nmr techniques.
      Thalifaberidine [1], thalifaberine [6], and thalifasine [7] showed cytotoxic
      activity against several human cancer cell lines, as well as antimalarial
      activity.

PMID- 7528788
TI  - The B cell repertoire in experimental allergic neuritis involves multiple myelin
      proteins and GM1.
AB  - Experimental allergic neuritis (EAN) is a T cell mediated disease associated with
      inflammation and demyelination of peripheral nerves. EAN is an experimental model
      of Guillain-Barre syndrome. The peripheral nerve myelin components P2 and P0
      represent major neuritogens, but the diversity and quantity of B cell responses
      in EAN are unknown. Lewis rats were immunized with bovine peripheral nerve myelin
      (BPM), and levels of B cells secreting IgM and IgG antibodies to BPM, P2 and P0,
      the glycolipid GM1 and five peptides of myelin-associated glycoprotein (MAG) were
      determined. Already on day 7 post-immunization (p.i.), i.e. before the onset of
      clinical EAN, lymph nodes contained elevated levels of cells secreting IgM
      antibodies of all specificities examined. Maximum numbers of IgG antibodies
      secreting cells were generally reached at the height of clinical disease. The
      numbers of cells secreting IgG antibodies to BPM, P2, P0, GM1 and MAG peptides
      were also elevated before disease onset, but they were mostly higher than those
      of IgM antibodies and they reached their maximum only after recovery. The results
      imply that EAN is associated with strong B cell responses to all myelin antigens
      under study without restriction to any immunodominant myelin component or MAG
      peptides.

PMID- 7528790
TI  - Gramicidin perforated patch-clamp technique reveals glycine-gated outward
      chloride current in dissociated nucleus solitarii neurons of the rat.
AB  - 1. The inhibitory response of exogenously applied glycine was investigated in
      freshly dissociated rat nucleus tractus solitarii neurons under whole cell
      configuration using new perforated patch-clamp technique termed "gramicidin
      perforated patch technique," which maintains intact intracellular Cl-
      concentrations. 2. Using the gramicidin perforated patch technique, at a holding
      potential (VH) of -45 mV, glycine induced outward currents in a concentration
      dependent manner with a EC50 of 4.0 x 10(-5) M and at a Hill coefficient of 1.5.
      In contrast, using the nystatin perforated patch technique, glycine induced
      inward currents at the same VH in a concentration-dependent manner with an EC50
      of 4.9 x 10(-5) M and at a Hill coefficient of 1.2. 3. The glycine-induced
      outward currents were blocked by strychnine in a concentration dependent manner
      with an IC50 of 2.2 x 10(-8) M. The blockade was competitive. 4. The current
      voltage relationship for the 10(-5) M glycine response showed a clear outward
      rectification. 5. Ten-fold change of extracellular Cl- with a large impermeable
      anion resulted in a 65 mV shift of the reversal potential of glycine-induced
      currents (EGly), indicating that the membrane behaves like a Cl- electrode in the
      presence of glycine. 6. The intracellular Cl- activity calculated from the EGly
      ranged from 7.3 to 18.2 mM, with a mean value of 13.3 mM. 7. The values of EGly
      in the individual neurons were significantly negative to the resting membrane
      potentials, suggesting the existence of active transport of Cl-.

PMID- 7528789
TI  - The 9L rat brain tumor model for pre-clinical investigation of radiation
      chemotherapy interactions.
AB  - The rat 9L gliosarcoma brain tumor model has been used for more than thirty years
      to investigate a variety of potential therapeutic agents, combinations,
      schedules, and approaches that might be applicable to the management of high
      grade malignant brain tumors in man. When tumor cells are implanted
      intracerebrally, a solid tumor grows until its mass results in the death of the
      animal, typically between 20 and 30 days postinoculation. Radiation therapy
      (either single or fractionated doses) is effective at prolonging survival in a
      dose-dependent manner. Numerous cancer chemotherapeutic agents, by a variety of
      doses, schedules, and routes of delivery, have demonstrated therapeutic efficacy
      in the 9L model. The combination of radiation and agents such as AZQ, BCNU,
      bleomycin, and cis-platinum has resulted in prolongation of survival that is
      significantly better than either agent used alone, without exceeding the
      tolerance of critical normal tissues. These pre-clinical data suggest that
      combining standard fractionated radiation therapy with appropriate concomitant
      cytotoxic chemotherapeutic agents might benefit patients with high-grade brain
      tumors.

PMID- 7528795
TI  - Prostate-specific antigen in screening of prostate cancer.
AB  - Prostate-specific antigen (PSA) is a well-characterized human prostate-specific
      glycoprotein. PSA has been shown to be the most effective immunohistologic marker
      for prostate cancer, as well as the most useful serologic test in staging and
      monitoring prostate cancer and in early detection of recurrent disease. The
      greatest clinical value of PSA is an aid for early detection of prostate cancer.
      Recent studies have indicated that PSA-based screening of the older population
      for organ-confined early-stage prostate cancer is an acceptable, practical, and
      reliable modality. The accuracy of PSA screening is within the same range as the
      mammogram. The cost-effectiveness of PSA is comparable to other cancer screening
      tests. Although the increase in the patient's survival due to PSA-based detection
      of early prostate cancer remains to be documented, it is generally agreed that
      the PSA test along with digital rectal examination (DRE) should be included in
      the annual physical examination for men 50 years of age or older. High-risk men
      are urged to commence at age 40. Asymptomatic men who have both a negative DRE
      and normal PSA blood test need only to continue an annual DRE and PSA check-up.
      Men who have a negative DRE and elevated PSA, and all those who have a suspicious
      DRE regardless of PSA results, should undergo further diagnostic workup, such as
      transrectal ultrasonography with biopsy of visible lesions. The cure rate is high
      with timely treatment, when prostate cancer is detected while still confined to
      the prostate.

PMID- 7528791
TI  - Participation of voltage-gated conductances on the response succeeding inhibitory
      synaptic potentials in the crayfish slowly adapting stretch receptor neuron.
AB  - 1. We examined the contribution of voltage-gated conductances to inhibitory
      postsynaptic potential (IPSP) effects under current clamp in silent and spiking
      slowly adapting stretch receptor neurons (SN1s) in the slow receptor muscle of
      the crayfish Procambarus. The receptor exemplifies the simplest inhibitory neural
      circuit, with one presynaptic and one postsynaptic neuron. The effects of
      synaptic inhibition were compared with the outcome of hyperpolarizing current
      pulses. Because pulse effects were exclusively due to postsynaptic mechanisms, an
      estimation of the synaptic or extrasynaptic origin of the results of IPSP was
      possible. 2. Inhibition by single IPSPs increased gradually with the time elapsed
      from the preceding spike in 60% of the spiking SN1s. However, early IPSP arrivals
      were exclusively excitatory in the rest of the cases. Inhibition was restricted
      to a single expanded SN1 interspike interval, but the early excitation and the
      postinhibitory rebound lasted several intervals. Rebound was invariably present;
      it was the only consequence of IPSPs in silent receptors and could be extremely
      long lasting (> 25 s). 3. The membrane potential of the SN1 neuron was clamped at
      hyperpolarized values (greater than -65 mV) by prolonged IPSP barrages at high
      rate (> 20/s). A prominent depolarizing sag and a gradual reduction of the IPSP
      amplitude were observed with prolonged presynaptic stimulation. There were
      subthreshold IPSP amplitude oscillations consisting of gradual increases and
      decreases of the post-IPSP peak depolarization at lower presynaptic rates. IPSP
      amplitude variations (< or = 10 mV) were primarily due to larger local responses.
      4. Essentially all IPSP effects were mimicked by hyperpolarizing pulses. Sag was
      also evoked by pulses and was accompanied by a gradual conductance increase
      preceded by a brief initial drop. Sag and rebound were markedly reduced by Cs+ (2
      mM) and tetrodotoxin (1 microM) and less by Ba2+ (5 mM) or tetraethylammonium (25
      mM) superfusion. Both were somewhat decreased by acetylcholine (30 microM), which
      also markedly depolarized and accelerated firings, results which were usually
      reduced by atropine (10 microM). 5. In conclusion, IPSP and hyperpolarizing pulse
      effects were essentially identical, implying that extrasynaptic membrane
      properties were decisive. Interestingly, net excitatory consequences were usual,
      effectively increasing sensitivity and reducing the sensory threshold.
      Pharmacological evidence is provided suggesting that the hyperpolarization
      activated current, IQ, and also probably the K+ M-current, the A-current, and the
      low-threshold, persistent Na+ conductances participate in sag and rebound
      genesis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7528792
TI  - Substance P elevates intracellular calcium in both neurons and glial cells from
      the dorsal horn of the spinal cord.
AB  - 1. We used microfluorimetric measurement of [Ca2+]i to identify substance P
      sensitive cells acutely isolated from the dorsal horn of neonatal rats. We then
      used morphological, physiological, and immunocytochemical criteria to delineate
      two distinct populations of substance P-sensitive dorsal horn cells. 2. One
      population of cells with small-diameter cell bodies and many fine processes
      responds to substance P by releasing Ca2+ from internal stores. Many of these
      cells express the O4 surface antigen, and are thus likely to be glial cells,
      probably from the oligodendrocyte lineage. None of the cells with glial
      attributes respond to N-methyl-D-aspartate (NMDA), providing further evidence
      that they are nonneuronal. 3. In a second population of dorsal horn cells,
      substance P elevates [Ca2+]i by promoting Ca2+ entry. This class of cells is
      morphologically distinct from substance P-sensitive glial cells in that it
      exhibits large-diameter cell bodies, has smooth tapering processes, and is
      sensitive to NMDA. This second class of cells is therefore likely to consist of
      neurons. 4. Consistent with the identification of different mechanisms of Ca2+
      elevation in the two cell types, the kinetics of the substance P-evoked release
      of Ca2+ in glial cells is very different than the kinetics of the Ca(2+)-entry
      response evoked in neurons. The glial cell response had a rapid average rate of
      rise (mean = 260 +/- 105 nM/s) and relatively brief duration (mean = 7.6 +/- 2.2
      s) whereas the neuronal response had a much slower rate of rise (mean = 10 +/- 9
      nM/s) with a much longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528793
TI  - Ligand-gated currents of alpha and beta ganglion cells in the cat retinal slice.
AB  - 1. We studied the receptor pharmacology of the ligand-gated currents of ON- and
      OFF- alpha and beta ganglion cells in a cat retinal slice preparation using the
      whole cell recording variation of the patch-clamp technique. Cat retinal slices
      were cut in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer
      and incubated in a bicarbonate-buffered solution. Ganglion cells were voltage
      clamped at -70 mV in HEPES-buffered Ringer solution. The pipette solution
      contained a low concentration of Cl- to distinguish mixed cationic from Cl(-)
      mediated conductances, and Lucifer yellow (0.5%) was included for identification
      of the cell type. 2. In Ringer solution containing 1.2 mM Mg2+, current-voltage
      (I-V) curves of responses to the excitatory amino acid agonist (EAA) N-methyl-D
      aspartate (NMDA) (200 microM) revealed a J-shaped function. In Mg(2+)-free Ringer
      solution containing 200 microM Cd2+ to block synaptic transmission, NMDA (200
      microM) elicited an inward current 5-8 times larger at -70 mV. In both conditions
      I-V curves of the NMDA-induced currents reversed near 0 mV. These results suggest
      that there are NMDA EAA receptors present directly on the dendrites of alpha and
      beta ganglion cells. Responses to NMDA were blocked by +/- 2-amino-7
      phosphonoheptanoic acid (AP7) (200 microM). 3. In Ringer solution containing 200
      1,000 microM Cd2+ to block synaptic transmission, both ON- and OFF- alpha and
      beta cells responded to kainic acid (10-50 microM), alpha-amino-3-hydroxy-5
      methylisoxazole-4-proprionic acid (AMPA) (20-70 microM), and quisqualic acid (0.1
      30 microM) with inward currents that reversed near 0 mV. These responses were
      blocked by the quinoxaline EAA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) (10 microM). The metabotropic agonists 1-aminocyclopentane-1,3
      dicarboxylic acid (ACPD) (25 microM) and L-2-amino-4-phosphonobutyric acid (L
      APB) (50 microM) and L-2-amino-4-phosphonobutyric acid (L-APB) (50 microM) in the
      presence of Cd2+ evoked little or no response for all cells tested. 4. In the
      presence of Cd2+, alpha and beta cells responded to gamma-amino-butyric acid
      (GABA) (200 microM) and glycine (200 microM) with inward currents that reversed
      near -35 mV, the calculated chloride equilibrium potential Ecl. Responses to GABA
      and glycine were both strongly desensitizing. (+)Bicuculline methyl chloride (20
      microM) blocked an average of 90% of the inward current evoked by 200 microM GABA
      on all ganglion cell types.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7528796
TI  - Successful use of two rapid HCV assays in a high prevalence Romanian population.
AB  - Hepatitis C virus (HCV) infection is of significant concern for recipients of
      blood and for patients who share resources such as hemodialysis machines. In many
      developing countries and in small peripheral laboratories, facilities and
      capabilities to perform ELISA assays may not be available. We evaluated two newly
      marketed rapid HCV serologic assays to determine their ability and suitability to
      detect antibodies to HCV in hemodialysis patients in Bucharest, Romania. Results
      indicated that both the Rapid HCV Ab assay (Clonatec, Paris, France) and the HCV
      SPOT (Diagnostic Biotechnology, Singapore) detected HCV antibody in 23 of 27
      patients. All 23 samples were also reactive by a routine HCV ELISA and were
      confirmed using a supplemental assay (HCV blot, Diagnostic Biotechnology,
      Singapore). Only one sample produced equivocal result by the Rapid HCV Ab assay.
      In this high prevalence population (90%), the use of recombinant or synthetic
      peptide rapid HCV assays has been successful in detecting confirmed positive
      cases of HCV and has shown excellent correlation with an ELISA screening assay.
      The tests are simple to perform, can be performed by individuals with minimal
      training, and have built-in quality control measures. We conclude that these
      tests may have important applicability in certain testing situations.

PMID- 7528797
TI  - The extracellular matrix components, tenascin and fibronectin, in Hirschsprung's
      disease: an immunohistochemical study.
AB  - Previous in vitro studies have suggested that successful neural crest cell
      migration in the developing gut could be influenced by the composition of the
      extracellular matrix components, tenascin and fibronectin. The authors aimed to
      gain insight into the pathogenesis of Hirschsprung's disease (HD) by studying the
      distribution of tenascin and fibronectin in bowel specimens of patients with HD.
      Immunohistochemical examination was performed in specimens from 10 HD patients (8
      aganglionic, 5 transitional, and 10 normoganglionic zones) and 18 age- and site
      matched controls undergoing other types of gastrointestinal surgery. The
      distribution of tenascin was restricted to the basement membranes of the smooth
      muscle and vasculature, and in the basement membranes surrounding neuronal
      ganglia in all the controls and in 10 proximal normoganglionic HD specimens. More
      intense tenascin immunofluorescence was observed in the smooth muscle basement
      membranes of the muscularis externa of eight aganglionic and five transitional
      zones of HD. Wide-spread distribution of fibronectin was found in all the
      basement membranes as well as in the lamina propria and submucosa of all control
      and 10 normoganglionic HD sections. However, more intense immunofluorescence with
      fibronectin was observed in all the layers of eight aganglionic and five
      transitional zones of HD specimens. The present findings show that the
      mesenchymal and basement membrane extracellular matrix constitution is abnormal
      in the affected bowel of HD. Although a causal relationship has not been
      demonstrated, corroborative evidence from earlier animal experiments in other
      studies suggests that the extracellular matrix abnormalities may contribute to
      the pathogenesis of HD.

PMID- 7528794
TI  - Meeting educational needs with a poster display.

PMID- 7528798
TI  - Cystic mesothelioma of the peritoneum: a rare cause of 'ascites' in children.
AB  - A 2-year-old girl presented with a 3-month history of progressive painless
      abdominal distension. Results of the clinical examination suggested massive
      ascites, but no other symptoms or signs could be elicited. There was no history
      of any other illness preceding the onset of distension. Ultrasonography and a
      computed tomography scan confirmed gross ascites, with multiple thin-walled
      loculi throughout the abdomen, from the diaphragm to the pelvis. The preoperative
      diagnosis was intraabdominal lymphangioma. During laparotomy, multiple
      transparent cysts were found throughout the peritoneum. There was no evidence of
      malignancy in any organ, and the cysts appeared almost completely avascular.
      Histological and ultrastructural appearances were those of benign cystic
      mesothelioma of the peritoneum, a condition that hitherto has been recognized
      only in adults. It is thought to represent a borderline variant between a truly
      benign adenomatoid lesion and the better-known malignant mesothelioma. The
      experience with adult cases suggests a high potential for recurrence but no
      progression to malignancy. It is possible that some cases of intraabdominal
      lymphangioma may have been misdiagnosed in the past; future cases should be fully
      evaluated, both immunohistochemically and ultrastructurally, to establish the
      true incidence of mesothelial proliferative disease in children.

PMID- 7528800
TI  - Failure to remove the resected tube in salpingectomy for tubal pregnancy. A case
      report.
AB  - Operative laparoscopy has offered a revolution in gynecologic surgery. However,
      as with all new techniques, unique complications will be found. We present a case
      in which the surgical specimen, an ectopic gestation, was set aside while
      bleeding was addressed. Upon return to where the specimen was placed, it was
      found that the specimen had "wandered" away and could not be retrieved
      laparoscopically. Suggestions for the management of this and similar occurrences
      are offered.

PMID- 7528799
TI  - [Studies on the Nepalese crude drugs. XIX. On the flavonoid and phenylethanoid
      constituents of the root of Scutellaria repens Buch.-Ham. ex D. Don].
AB  - From the root of Scutellaria repens Buch.-Ham ex D. Don, two new flavonoids (10,
      11) and three new phenylethanoids (12-14) were isolated, together with nine known
      compounds. The structures of 10-14 were shown to be 5,7,2'-trihydroxy-6,8
      dimethoxyflavone, O-5-hydroxy-6,8-dimethoxyflavone-7-yl beta-D
      glucuronopyranoside, O-2-(3-hydroxy-4-methoxyphenyl)ethyl O-2,3-di-O-acethyl
      alpha-L-rhamnopyranosyl- (1-->3)-(4-O-trans-feruloyl)-beta-D-glucopyranoside, O-2
      (3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-cis
      feruloyl)-beta-D-glu cop yranoside and O-2-(3-hydroxy-4-methoxyphenyl)-ethyl O
      2,3-di-O-acethyl-alpha-L-rhamnopyranosyl- (1-->3)-(4-O-cis-feruloyl)-beta-D-
      glucopyranoside, respectively, on the basis of the chemical and spectral data.

PMID- 7528802
TI  - A voltage-sensitive cation channel present in clusters in lobster skeletal muscle
      membrane.
AB  - The single channel properties of a voltage-sensitive cation channel are described
      in a study of ion channel activity in enzymatically induced blebs of lobster
      skeletal muscle membrane. This cation channel, one of several that are
      spontaneously active in excised patches from bleb membrane, can be distinguished
      from other channels on the basis of its large single channel conductance (293
      pS), voltage-sensitive gating properties, the presence of a subconductance state
      of the fully open channel, and a weak selectivity for K > Na. At hyperpolarizing
      voltages, this channel displays flickering or bursting behavior, and a single
      state of the fully open channel is observed. At depolarizing voltages, the mean
      channel open time increases and a second longer-lived open state is observed. The
      voltage dependence of the mean channel open time and the linear i-V relation of
      this channel predict that the macroscopic current carried through this cation
      channel would be outwardly rectifying. Channels of this type are infrequently
      observed in this preparation, but when present in the patch are often present in
      multiple copies. We describe a statistical test for examining the clustering of
      ion channels in excised patches of membrane. The result of this test shows that
      the cation channels appear in clusters in the blebs.

PMID- 7528801
TI  - Nucleotide Regulation of a calcium-activated cation channel in the rat insulinoma
      cell line, CRI-G1.
AB  - The nucleotide regulation of a calcium-activated nonselective cation (Ca-NS+)
      channel has been investigated in the rat insulinoma cell line CRI-G1. The
      activity of the channel is reduced by both AMP and ADP (1-100 microM) in a
      concentration-dependent manner, with AMP being more potent than ADP. At lower
      concentrations (0.1-5 microM), both ADP and AMP activate the channel in some
      patches. Examination of the nucleotide specificity of channel inhibition
      indicates a high selectivity for AMP over the other nucleotides tested with a
      rank order of potency of AMP > UMP > CMP > or = GMP. Cyclic nucleotides also
      modulate channel activity in a complex, concentration-dependent way. Cyclic AMP
      exhibits a dual effect, predominantly increasing channel activity at low
      concentrations (0.1-10 microM) and reducing it at higher concentrations (100
      microM and 1 mM). Specificity studies indicate that the cyclic nucleotide site
      mediating inhibition of channel activity exhibits a strong preference for cyclic
      AMP over cyclic GMP, with cyclic UMP being almost equipotent with cyclic AMP.
      Cyclic IMP and cyclic CMP are not active at this site. The cyclic nucleotide site
      mediating activation of the channel shows much less nucleotide specificity than
      the inhibitory site, with cyclic AMP, cyclic GMP and cyclic IMP being almost
      equally active.

PMID- 7528803
TI  - Electrically induced fusion of mammalian cells in the presence of polyethylene
      glycol.
AB  - Chinese Hamster Ovary (CHO) cells were fused by subjecting cell suspensions to an
      exponentially decaying electric pulse in the presence of polyethylene glycol
      (PEG), Dextran or Ficoll. PEG (MW 1,000, 3,350, 8,000, 10,000 and 18,500),
      Dextran (MW 71,200) and Ficoll (MW 400,000) were added to the pulsing medium. A
      single exponential electric pulse with peak field strength of 4 kV/cm, and a half
      time of 0.72 msec was used. The combination of two techniques, PEG-induced fusion
      and electrofusion, resulted in highly efficient fusion of CHO cells. Fusion
      yields (FY) at different concentrations of these polymers were measured using
      phase-contrast microscopy. FY was highly dependent on the concentration of PEG in
      media, while the presence of Dextran and Ficoll had no influence on fusion yield.
      PEG with MW 8,000 was found to be the most effective in causing cell aggregation,
      and to give the highest FY (40%). An optimal concentration for fusion was found
      for PEG of each molecular weight. Diluting cells suspended in higher
      concentrations of PEG to these optimal concentrations after the pulse application
      regained the optimal FY. It was concluded that PEG-induced prepulse aggregation
      and moderate cell swelling immediately after the pulse were important factors in
      achieving high fusion yields.

PMID- 7528805
TI  - Permeabilization of the plasma membrane of L1210 mouse leukemia cells using
      lithotripter shock waves.
AB  - Permeabilization of L1210 cells by lithotripter shock waves in vitro was
      monitored by evaluating the accumulation of fluorescein-labeled dextrans with a
      relative molecular mass ranging from 3,900-2,000,000. Incubation with labeled
      dextran alone caused a dose- and time-dependent increase in cellular fluorescence
      as determined by flow cytometry, with a vesicular distribution pattern in the
      cells consistent with endocytotic uptake. Shock wave exposure prior to incubation
      with labeled dextran revealed similar fluorescence intensities compared to
      incubation with labeled dextran alone. When cells were exposed to shock waves in
      the presence of labeled dextran, mean cellular fluorescence was further
      increased, indicating additional internalization of the probe. Confocal laser
      scanning microscopy confirmed intracellular fluorescence of labeled dextran with
      a diffuse distribution pattern. Fluorescence-activated cell sorting with
      subsequent determination of proliferation revealed that permeabilized cells were
      viable and able to proliferate. Permeabilization of the membrane of L1210 cells
      by shock waves in vitro allowed loading of dextrans with a relative molecular
      mass up to 2,000,000. Permeabilization of tumor cells by shock waves provides a
      useful tool for introducing molecules into cells which might be of interest for
      drug targeting in tumor therapy in vivo.

PMID- 7528806
TI  - Are PSA 8-10 particularly worrisome numbers?

PMID- 7528804
TI  - Voltage-activated hydrogen ion currents.

PMID- 7528808
TI  - Phylogeny of the Drosophila obscura species group deduced from mitochondrial DNA
      sequences.
AB  - Approximately 2 kb corresponding to different regions of the mtDNA of 14
      different species of the obscura group of Drosophila have been sequenced. In
      spite of the uncertainties arising in the phylogenetic reconstruction due to a
      restrictive selection toward a high mtDNA A+T content, all the phylogenetic
      analysis carried out clearly indicate that the obscura group is formed by, at
      least, four well-defined lineages that would have appeared as the consequence of
      a rapid phyletic radiation. Two of the lineages correspond to monophyletic
      subgroups (i.e., affinis and pseudoobscura), whereas the obscura subgroup remains
      heterogeneous assemblage that could be reasonably subdivided into at least two
      complexes (i.e., subobscura and obscura).

PMID- 7528807
TI  - Biased distribution of adenine and thymine in gene nucleotide sequences.
AB  - We analyzed occurrences of bases in 20,352 introns, exons of 25,574 protein
      coding genes, and among the three codon positions in the protein-coding
      sequences. The nucleotide sequences originated from the whole spectrum of
      organisms from bacteria to primates. The analysis revealed the following: (1) In
      most exons, adenine dominates over thymine. In other words, adenine and thymine
      are distributed in an asymmetric way between the exon and the complementary
      strand, and the coding sequence is mostly located in the adenine-rich strand. (2)
      Thymine dominates over adenine not only in the strand complementary to the exon
      but also in introns. (3) A general bias is further revealed in the distribution
      of adenine and thymine among the three codon positions in the exons, where
      adenine dominates over thymine in the second and mainly the first codon position
      while the reverse holds in the third codon position. The product
      (A1/T1)x(A2/T2)x(T3/A3) is smaller than one in only a few analyzed genes.

PMID- 7528810
TI  - Production of RNA by a polymerase protein encapsulated within phospholipid
      vesicles.
AB  - Catalyzed polymerization reactions represent a primary anabolic activity of all
      cells. It can be assumed that early cells carried out such reactions, in which
      macromolecular catalysts were encapsulated within some type of boundary membrane.
      In the experiments described here, we show that a template-independent RNA
      polymerase (polynucleotide phosphorylase) can be encapsulated in dimyristoyl
      phosphatidylcholine vesicles without substrate. When the substrate adenosine
      diphosphate (ADP) was provided externally, long-chain RNA polymers were
      synthesized within the vesicles. Substrate flux was maximized by maintaining the
      vesicles at the phase transition temperature of the component lipid. A protease
      was introduced externally as an additional control. Free enzyme was inactivated
      under identical conditions. RNA products were visualized in situ by ethidium
      bromide fluorescence. The products were harvested from the liposomes,
      radiolabeled, and analyzed by polyacrylamide gel electrophoresis. Encapsulated
      catalysts represent a model for primitive cellular systems in which an RNA
      polymerase was entrapped within a protected microenvironment.

PMID- 7528809
TI  - Evolution of secondary structure in the family of 7SL-like RNAs.
AB  - Primate and rodent genomes are populated with hundreds of thousands copies of Alu
      and B1 elements dispersed by retroposition, i.e., by genomic reintegration of
      their reverse transcribed RNAs. These, as well as primate BC200 and rodent 4.5S
      RNAs, are ancestrally related to the terminal portions of 7SL RNA sequence. The
      secondary structure of 7SL RNA (an integral component of the signal recognition
      particle) is conserved from prokaryotes to distant eukaryotic species. Yet only
      in primates and rodents did this molecule give rise to retroposing Alu and B1
      RNAs and to apparently functional BC200 and 4.5S RNAs. To understand this
      transition and the underlying molecular events, we examined, by comparative
      analysis, the evolution of RNA structure in this family of molecules derived from
      7SL RNA. RNA sequences of different simian (mostly human) and prosimian Alu
      subfamilies as well as rodent B1 repeats were derived from their genomic
      consensus sequences taken from the literature and our unpublished results
      (prosimian and New World Monkey). RNA secondary structures were determined by
      enzymatic studies (new data on 4.5S RNA are presented) and/or energy minimization
      analyses followed by phylogenetic comparison. Although, with the exception of
      4.5S RNA, all 7SL-derived RNA species maintain the cruciform structure of their
      progenitor, the details of 7SL RNA folding domains are modified to a different
      extent in various RNA groups. Novel motifs found in retropositionally active RNAs
      are conserved among Alu and B1 subfamilies in different genomes. In RNAs that do
      not proliferate by retroposition these motifs are modified further. This
      indicates structural adaptation of 7SL-like RNA molecules to novel functions,
      presumably mediated by specific interactions with proteins; these functions were
      either useful for the host or served the selfish propagation of RNA templates
      within the host genome.

PMID- 7528813
TI  - Oligodendroglial cyclic AMP response element-binding protein: a member of the
      CREB family of transcription factors.
AB  - Several laboratories have shown that cyclic AMP (cAMP) plays an important role in
      inducing oligodendrocyte differentiation and myelin synthesis. Our previous
      results have shown that oligodendrocytes contain a nuclear protein that binds to
      the DNA sequence TGACGTCA or cAMP response element (CRE) known to be involved in
      the transcriptional regulation of cAMP-responsive genes. In this report the
      oligodendroglial CRE-binding protein was further identified by using two
      different antibodies which specifically recognize the CRE-binding protein known
      as CREB. In DNA-shift assays CREB-1(X-12) antibody interacted with the CRE
      protein complexes resulting in further retardation ("super shift") of the
      mobility of the bands in the gels. Immunoprecipitation of oligodendroglial
      nuclear extracts with CREB(240) antibody prior to the DNA binding assays resulted
      in a lack of formation of CRE-protein complexes. In addition immunoreaction with
      CREB(240) antibody identified the CRE-binding species as a 45 kDa phosphoprotein.
      Immunocytochemical staining with CREB(240) antibody in oligodendrocytes from 10-,
      14-, and 18-day-old and adult rats indicated that this protein is expressed
      before the appearance of myelin basic protein (MBP) which was used as a marker of
      myelin synthesis. Collectively, these observations support our previous results
      and indicate that the oligodendroglial CRE-binding protein species is highly
      homologous to the CREB protein. The developmental expression of this CREB protein
      supports the idea of a possible role during the early stages of oligodendrocyte
      differentiation preceding the peak of myelin synthesis in rat CNS.

PMID- 7528812
TI  - Tracing the spread of fibronectin type III domains in bacterial glycohydrolases.
AB  - The evolutionary spread of 22 fibronectin type III (Fn3) sequences among a dozen
      bacterial enzymes has been traced by searching databases with the non-Fn3 parts
      of the enzyme sequences. Numerous homologues were found that lacked the Fn3
      domains. In each case the related sequences were aligned, phylogenetic trees were
      constructed, and the occurrences of Fn3 units on the trees were noted. Comparison
      with phylogenetic trees prepared from the Fn3 segments themselves allowed
      inferences to be made about when the Fn3 units were shuffled into their present
      positions.

PMID- 7528811
TI  - The mitochondrial ribosomal RNA genes of the nematodes Caenorhabditis elegans and
      Ascaris suum: consensus secondary-structure models and conserved nucleotide sets
      for phylogenetic analysis.
AB  - The small- and large-subunit mitochondrial ribosomal RNA genes (mt-s-rRNA and mt
      l-rRNA) of the nematode worms Caenorhabditis elegans and Ascaris suum encode the
      smallest rRNAs so far reported for metazoa. These size reductions correlate with
      the previously described, smaller, structurally anomalous mt-tRNAs of C. elegans
      and A. suum. Using primer extension analysis, the 5' end nucleotides of the mt-s
      rRNA and mt-l-rRNA genes were determined to be adjacent to the 3' end nucleotides
      of the tRNA(Glu) and tRNA(His) genes, respectively. Detailed, consensus secondary
      structure models were constructed for the mt-s-rRNA genes and the 3' 64% of mt-l
      rRNA genes of the two nematodes. The mt-s-rRNA secondary-structure model bears a
      remarkable resemblance to the previously defined universal core structure of E.
      coli 16S rRNA: most of the nucleotides that have been classified as variable or
      semiconserved in the E. coli model appear to have been eliminated from the C.
      elegans and A. suum sequences. Also, the secondary structure model constructed
      for the 3' 64% of the mt-l-rRNA is similar to the corresponding portion of the
      previously defined E. coli 23S rRNA core secondary structure. The proposed C.
      elegans/A. suum mt-s-rRNA and mt-l-rRNA models include all of the secondary
      structure element-forming sequences that in E. coli rRNAs contain nucleotides
      important for A-site and P-site (but not E-site) interactions with tRNAs. Sets of
      apparently homologous sequences within the mt-s-rRNA and mt-l-rRNA core
      structures, derived by alignment of the C. elegans and A. suum mt-rRNAs to the
      corresponding mt-rRNAs of other eukaryotes, and E. coli rRNAs were used in
      maximum-likelihood analyses. The patterns of divergence of metazoan phyla
      obtained show considerable agreement with the most prevalent metazoan divergence
      patterns derived from more classical, morphological, and developmental data.

PMID- 7528814
TI  - The interleukin-1-induced increase of substance P in sympathetic ganglia is not
      mediated by ciliary neurotrophic factor.
AB  - Interleukin-1 (IL-1) induction of substance P (SP) in cultured sympathetic
      ganglia requires a soluble intermediate molecule that is present in IL-1
      conditioned medium (IL-1CM). One of the required intermediates is leukemia
      inhibitory factor (LIF; Shadiack et al., J Neurosci 13:2601-2609, 1993). In the
      present study we have examined the possibility that ciliary neurotrophic factor
      (CNTF) is another intermediate involved in the IL-1 induction of sympathetic SP.
      CNTF mimics the action of IL-1CM by raising both SP and choline acetyltransferase
      activity--actions that are blocked by a specific neutralizing antiserum for CNTF.
      However, IL-1CM and CNTF differ in their response to depolarizing agents: while
      KCl (40 mM) blocks the action of IL-1CM (and LIF), it enhances the action of
      CNTF. Furthermore, neither CNTF bioactivity nor CNTF protein is detected in IL
      1CM. Neutralizing antiserum to CNTF fails to block the action of either IL-1 or
      IL-1CM, suggesting that neither a soluble nor a membrane-bound form of the
      molecule is active in direct response to IL-1 action. While Northern blots
      confirm the presence of both CNTF and CNTF receptor mRNA in neonatal ganglia,
      neither culturing nor IL-1 treatment alters these mRNA levels. These data taken
      together suggest that while CNTF is present and possibly active in sympathetic
      ganglia, it is not a mediator of the IL-1 induction of SP.

PMID- 7528815
TI  - Regulation of nitric oxide synthase activity in cortical slices by excitatory
      amino acids and calcium.
AB  - Nitric oxide synthase (NOS) activity was determined in adult rat frontal cortex
      and hippocampus by measuring the conversion of L-[3H]arginine to L
      [3H]citrulline. N-methyl-D-aspartate (NMDA), but not kainate or alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate (AMPA), stimulated NOS activity. This
      effect was concentration dependent (EC50 approximately 30 microM) and was
      inhibited by tetrodotoxin, EGTA, N omega-nitro-L-arginine (NOARG), Mg2+,
      phencyclidine, and (cis)-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755),
      but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). NOS activity was
      increased to an even greater extent by the calcium ionophores ionomycin and
      A23187 and by depolarization with 50 mM K+. Interestingly, neither caffeine nor 1
      aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), drugs that would be
      expected to increase intracellular Ca2+ concentration by release of Ca2+ from
      intracellular ryanodine- and inositol-1,4,5-trisphosphate-sensitive stores,
      respectively, had any significant effect on NOS activity. It is concluded that
      NOS can be activated by NMDA binding to a classic NMDA glutamate receptor subtype
      as well as by depolarization or other agents that increase the influx of
      extracellular Ca2+. The paradoxical lack of effect of caffeine, as well as the
      inhibitory effect of tetrodotoxin, are discussed.

PMID- 7528817
TI  - Mutations in demyelinating peripheral neuropathies support molecular model of
      myelin P0-glycoprotein extracellular domain.
AB  - Homophilic interactions of the major integral membrane protein of peripheral
      nerve myelin, P0-glycoprotein, are thought to mediate membrane adhesion and
      compaction. Molecular modeling of its extracellular domain (P0-ED), based on its
      resemblance to an immunoglobulin variable domain and on X-ray diffraction
      measurements of inter-membrane spacings of myelin, has suggested which amino acid
      sidechains may be involved in the homophilic adhesion. Recently identified point
      mutations in the human P0 gene result in amino acid substitutions in P0 protein
      and correlate with demyelinating motor and sensory neuropathies. The molecular
      model explains how these changes result in disrupted P0-P0 interactions;
      indicates how compensatory changes in amino acids, as occur in P0-ED of other
      species, preserve normal homophilic interactions; and predicts what other residue
      substitutions might underlie additional cases of demyelinating neuropathies.

PMID- 7528816
TI  - Inhibitors of N-linked oligosaccharide processing glucosidases interfere with
      oligodendrocyte differentiation in culture.
AB  - Previous studies have demonstrated that inhibitors of glycoprotein processing
      glucosidases interfere with the development of oligodendrocyte properties in
      primary cultures of embryonic rat brain cells (Bhat, J Neurosci Res 20:158-164,
      1988). The present study examines the effect of castanospermine, an inhibitor of
      the processing glucosidases, on the development and differentiation of isolated
      oligodendrocyte progenitor cells. Treatment of oligodendrocyte progenitors with
      castanospermine did not affect the developmental progression of the precursors to
      become committed oligodendrocytes as revealed by comparable increases in the
      percentages of cells positive for galactocerebroside (a surface marker for
      terminally differentiated oligodendrocytes) in control and drug-treated cultures.
      On the other hand, there was an impairment of the expression of differentiated
      properties of oligodendrocytes [i.e., sulfolipid synthesis, myelin basic protein
      (MBP)] and 2'3'-cyclic nucleotide 3'-phosphohydrolase in the drug-treated
      cultures. Immunocytochemical analysis with anti-MBP antibodies revealed a reduced
      number of MBP-positive cells in inhibitor-treated cultures. Furthermore, a
      majority of MBP-positive cells in such cultures displayed immunoreactive MBP in
      their cell body and not the processes, unlike in control cultures where both cell
      body and the processes of oligodendrocytes stained intensely for MBP. The strong
      inhibitory effect of castanospermine on the expression of oligodendrocyte
      specific activities was contrasted with a relatively smaller effect of
      swainsonine, a mannosidase inhibitor on oligodendrocyte differentiation. Both
      castanospermine and swainsonine, however, effectively blocked the formation of
      complex-type oligosaccharides, suggesting thereby a lack of correlation between
      the inhibition of the formation of complex-type oligosaccharides and
      oligodendrocyte differentiation. It is suggested, therefore, that early trimming
      reactions involving the removal of glucose residues from the high mannose
      oligosaccharides in the endoplasmic reticulum may be essential for the cell
      surface localization and function of glycoproteins critically involved in surface
      interactions of oligodendrocytes with each other and/or with the substratum.

PMID- 7528818
TI  - Transcription of the brain creatine kinase gene in glial cells is modulated by
      cyclic AMP-dependent protein kinase.
AB  - The brain creatine kinase (CKB) gene is expressed in a variety of tissues with
      highest expression seen in the brain. We have previously shown in primary rat
      brain cell cultures that CKB mRNA levels are high in oligodendrocytes and
      astrocytes and low in neurons (Molloy et al.: J Neurochem 59:1925-1932, 1992). In
      this report we show that treatment of human U87 glioblastoma cells with forskolin
      and IBMX, to elevate intracellular cAMP, induces expression of CKB mRNA from the
      transiently transfected rat CKB gene by 14-fold and also increases expression
      from the endogenous human CKB gene. This induction of CKB mRNA i) is due to
      increased transcription; ii) occurs rapidly (with maximal induction after 6 hr;
      iii) requires the activity of protein kinase A (PKA), but iv) does not require de
      novo protein synthesis and, in fact, is superinduced in the presence of
      cycloheximide. Given the role of oligodendrocytes in the energy-demanding process
      of myelination and of astrocytes in ion transport, these results have
      physiological significance, since they suggest that changes in cellular energy
      requirements in the brain during events, such as glial cell differentiation and
      increased neuronal activity, may in part be met by a cAMP-mediated modulation of
      CKB gene expression. Of particular importance is the possible modulation of CKB
      gene expression during myelinogenesis, since oligodendrocyte differentiation has
      been shown previously to be stimulated by increases in cAMP.

PMID- 7528819
TI  - Myelin basic protein mediates extracellular signals that regulate microtubule
      stability in oligodendrocyte membrane sheets.
AB  - Treatment of cultured oligodendrocytes with a monoclonal antibody to
      galactocerebroside (GalC) triggers a cascade of events including the
      redistribution of membrane surface GalC over internal domains of MBP and loss of
      microtubular structures within the sheets (Dyer and Benjamins: J Neurosci 8:4307
      4318, 1988; Dyer and Benjamins: J Neurosci Res 24:212-221, 1989). In this report,
      wild type and myelin basic protein (MBP)-deficient shiverer oligodendrocytes were
      used to study the possible relationships between these events, and specifically
      to determine if MBP mediates signals which destabilize microtubular assemblies in
      cultured oligodendrocytes. We now show that MBP and GalC, which are both
      initially Triton X-100 soluble, become Triton X-100 insoluble following anti-GalC
      binding and anti-GalC:GalC complex redistribution, suggesting that the surface
      anti-GalC: GalC complexes become associated with cytoplasmic MBP. Mediation of
      the signaling event by MBP is further demonstrated by 1) a decreased
      phosphorylation of MBP in wild type oligodendrocytes after antibody binding, and
      2) the absence of responses, such as GalC redistribution and microtubule loss, in
      MBP-deficient shiverer oligodendrocytes treated with anti-GalC. Continuous
      activation of the GalC/MBP pathway for 7 days in wild type oligodendrocytes
      results in enlarged cell bodies and production of numerous microprocesses, a
      morphology that is similar to MBP-deficient shiverer oligodendrocytes. A second
      signaling pathway which produces an opposite effect, i.e., the stabilization and
      apparent up-regulation of microtubular structures in cultured oligodendrocyte
      membrane sheets, remains functional in shiverer oligodendrocytes. Thus, MBP
      appears to be important for mediating extracellular signals that cause a loss of
      microtubular structures in oligodendrocyte membrane sheets and abnormal
      morphology.

PMID- 7528820
TI  - [A preliminary study of HCV infections with hemophilia and their family members].
AB  - 28 cases of hemophilia were examined for HCV infection status by using the Kehua
      anti-HCV ELISA kit of second generation. It was found that the infection rate was
      78.5% and the infection rate was even higher with patients who had received
      transfusions or preparations of coagulatory factors. 10 families of 15 patients
      were also investigated. It was found that of 15 hemophilia patients, 12 showed
      positive anti-HCV, while none of their 53 family members exhibited any positive
      anti-HCV. In 8 children of 9 couples no positive anti-HCV was found. Our results
      revealed that the hemophilia patient may get infected with HCV by receiving
      multiple transfusions or preparation of coagulatory factors. The risk of getting
      infected with HCV via daily-life contact including sexual contact is extremely
      low.

PMID- 7528821
TI  - Endoscopic diagnosis, treatment, and follow-up of tumours of the nose and
      sinuses.
AB  - In the last decade, a great deal of attention has been focused on functional
      endoscopic nasal surgery for chronic sinus disease. There has been less emphasis
      in regard to the obvious advantages of the endoscope for diagnosis, treatment,
      and follow-up of tumours of the nose and paranasal sinuses. This presentation
      discusses in detail the reasons that the endoscopic technique is useful when
      applied to diagnosis of benign or malignant lesions in these areas. This new
      technique can be used to remove benign tumours, avoiding the external excisions
      that often can be disfiguring to the patient. The endoscope is less useful for
      removal of malignant lesions unless they are very small and localized, but it can
      be used as a palliative measure. Early diagnosis of recurrence, especially for
      benign tumours, is possible, and further localized excision can result in the
      cure.

PMID- 7528822
TI  - Computer-generated presentations: current status and future directions.
AB  - The personal computer allows the user to create professional presentations as
      good as any created by commercially available services. With the new generation
      of inexpensive software, myriad fonts, layouts, graphics, and imported images can
      all be used by the novice. The technology is currently available that can project
      images directly from the computer, obviating the need for slides. This
      presentation will discuss the relative merits and costs of such systems and the
      problems that remain concerning implementation at a national level.

PMID- 7528823
TI  - [Analysis of lipopolysaccharide (LPS) from impermeability-type drug resistant
      Pseudomonas aeruginosa using new, highly-sensitive LPS staining method].
AB  - The specific ladder pattern on polyacrylamide gel electropholesis of
      lipopolysaccharide (LPS) extracted from Pseudomonas aeruginosa was clearly shown
      by using the complex methods of the PAS staining, re-periodate oxidation and then
      Ag-staining method. Accordingly, it was concluded that the new method was greatly
      useful for a detail analysis of LPS changes in Gram-negative bacteria. And it was
      shown by this method that no changes in LPS occurred between the impermeability
      type drug resistant P. aeruginosa mediated by R plasmid and a drug susceptible
      strain. The absence of changes indicated that the LPS of P. aeruginosa K-Ps102
      had not role in the mechanism of the high drug resistance.

PMID- 7528825
TI  - [Tumor marker in prostate cancer].

PMID- 7528824
TI  - [Tenascin expression in idiopathic interstitial pneumonia].
AB  - The expression of tenascin, a of extracellular matrix glycoprotein, was studied
      immunohistochemically in the lungs of 22 autopsy cases, including chronic
      idiopathic interstitial pneumonia (chronic IIP) associated with lung cancer (5
      cases), chronic IIP without lung cancer (6 cases), acute idiopathic interstitial
      pneumonia (acute IIP; 6 cases) and alveolar pneumonia (AP; 5 cases). In the
      honeycomb lesion of chronic IIP, tenascin expression was observed in the basement
      membrane of metaplastic epithelia and in the subepithelial stroma of thickened
      septa with fibrosis. In the non-honeycomb area of chronic IIP, tenascin was
      expressed in mildly thickened alveolar walls with fibrosis. The distribution of
      tenascin expression in chronic IIP associated with lung cancer resembled that in
      chronic IIP without lung cancer. In acute IIP, tenascin expression was observed
      in mildly thickened alveolar walls with fibrosis, in organizing hyaline
      membranes. In AP, tenascin was expressed in organizing exudate of alveoli and was
      scarcely observed in the alveolar wall. It is very possible that tenascin is
      associated with the fibrosing process and remodelling in IIP, and has a promoting
      effect in carcinogenesis in IIP lung.

PMID- 7528826
TI  - [Distribution of NADPH diaphorase-positive nerves in human penile tissue].
AB  - Recently, nitric oxide (NO) has been thought to be a neuronal messenger to evoke
      penile erection. NO synthase (NOS)-containing nerve fibers were identified and
      localized in human penile tissue, but detail distribution of NOS-containing nerve
      fibers in the human penis was unclear. In the present study we examined their
      distribution using histochemical staining of NADPH diaphorase (ND), which is a
      specific marker of neuronal NOS. In the crura penis some various sizes of ND
      positive nerve bundles were observed in the cavernous spaces. In the penile shaft
      large bundles (> 50 microns) decreased in number and were observed only near deep
      artery. There were abundant ND-positive nerve terminals with fine varicosity
      innervating both corpus cavernous smooth muscles and deep, dorsal and helicine
      arteries. In the wall of deep dorsal vein there were also many groups of ND
      positive fibers. Endothelium of deep artery and its large branches was clearly ND
      positive, but parts of endothelium of deep dorsal vein or corpus cavernous sinus
      were only faintly stained. Some of the dorsal penile nerve fibers were ND
      positive. In corpus spongiosum many ND-positive nerve fibers were observed and
      urethelium was clearly ND-positive. In conclusion, NO may have an important role
      in the function of both corpus cavernosum and corpus spongiosum because NOS
      containing nerve fibers were widely distributed in both cavernous tissues.

PMID- 7528827
TI  - [Improved hospital nursing service through review of routine procedures.
      Preoperative shaving is not necessary for all patients].

PMID- 7528828
TI  - The segregation of glutaryl-CoA dehydrogenase deficiency and Refsum syndrome in a
      family.

PMID- 7528829
TI  - Canavan disease: molecular basis of aspartoacylase deficiency.

PMID- 7528831
TI  - alpha 2-Macroglobulin, complement, and biologic defense: antigens, growth
      factors, microbial proteases, and receptor ligation.

PMID- 7528832
TI  - Expression and function of the complement membrane attack complex inhibitor
      protectin (CD59) on human breast cancer cells.
AB  - BACKGROUND: Normal human cells resist the lytic activity of homologous complement
      (C) by expressing inhibitory molecules on their cell membranes. Recently, it has
      become increasingly evident that information on C inhibitors on malignant tumor
      cells is crucial before considering any immunotherapeutic attempts with C
      activating antibodies. As one of the most potent inhibitors of C lysis is
      protectin (CD59), we have examined its expression and function on human breast
      cancer cells. EXPERIMENTAL DESIGN: Immunofluorescence microscopy was used to
      detect protectin expression on solid breast tumor samples (N = 12). Using
      immunoaffinity chromatography, protectin was isolated from the membranes of
      cultured MCF7 and T47D breast cancer cells. The purified proteins were
      incorporated into heterologous cells to study their C inhibitory activities. The
      reactivity of tumor cell protectins with terminal C complexes was examined by
      sucrose density ultracentrifugation analysis. A chromium release assay was used
      to study the effects of protectin neutralization on the sensitivity of MCF7 and
      T47D cells to C-mediated cytotoxicity. RESULTS: Protectin was found to be
      strongly expressed by all human breast cancer tumors examined. The affinity
      purified protectins had a glycophosphoinositollipid anchor and migrated in sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis as glycosylated smears of 19
      to 25 kilodaltons. Protectin isolated from T47D cells bound to nascent C5b-9
      complexes generated in human sera and inhibited C lysis of guinea pig
      erythrocytes when incorporated into their cell membranes. C-mediated killing of
      breast cancer cells could be significantly enhanced after treatment of the cells
      with F(ab')2 fragments of the anti-protectin monoclonal antibody YTH53.1.
      CONCLUSIONS: Human breast cancer cells resist C membrane attack by expressing
      protectin on their cell membranes. Neutralization of protectin on the surface of
      the tumor cells increases their sensitivity to C lysis.

PMID- 7528830
TI  - Restoration of peroxisome biogenesis in a peroxisome-deficient mammalian cell
      line by expression of either the 35 kDa or the 70 kDa peroxisomal membrane
      proteins.

PMID- 7528833
TI  - Zidovudine causes early increases in mitochondrial ribonucleic acid abundance and
      induces ultrastructural changes in cultured mouse muscle cells.
AB  - BACKGROUND: Zidovudine (azidothymidine, AZT) causes a toxic mitochondrial
      myopathy in AIDS patients with changes in mitochondrial (mt) DNA and
      mitochondrial structure. To determine early subcellular events in AZT myopathy in
      vitro we examined C2C12 myotubes treated with AZT (0.2, 2, 10 micrograms/ml) for
      up to 4 weeks. We identified AZT-induced effects on muscle intracellular
      compartments by determining the comparative abundance of selected myotube
      cytoplasmic and mtRNAs and mtDNA. EXPERIMENTAL DESIGN: RNA and DNA were extracted
      from cultured C2C12 myotubes, blotted and probed with cDNAs specific for the
      mitochondrial gene products cytochrome b and cytochrome c oxidase I, nuclear
      encoded sarcomeric troponin C, and cytoplasmic glyceraldehyde-3-phosphate
      dehydrogenase. Transmission electron microscopy was performed on parallel
      samples. RESULTS: After 4 weeks of AZT, cytochrome b and cytochrome c oxidase I
      mtRNA abundance increased to 64% and to 31% above respective control levels. No
      change occurred in mtDNA abundance or nuclear encoded glyceraldehyde-3-phosphate
      dehydrogenase mRNA compared with the nuclear encoded sarcomeric troponin C
      control. Transmission electron microscopy showed focal disruption of
      mitochondrial cristae with intramyocytic lipid droplets after 14 days of AZT
      treatment. CONCLUSIONS: Increased mtRNA abundance in absence of changes in mtDNA
      abundance suggests that early AZT toxicity to mitochondria may relate to defects
      in mtDNA replication or mtRNA transcription.

PMID- 7528834
TI  - Selective interaction of the calcium antagonist amlodipine with calcium channels
      in arteries of spontaneously hypertensive rats.
AB  - The mechanism of the antihypertensive action of the 1,4-dihydropyridine Ca2+
      antagonist amlodipine was investigated by measuring dihydropyridine receptor
      occupation and the contractile responses to Ca2+ channel activation in aortas and
      mesenteric arteries from spontaneously hypertensive rats (SHR) and normotensive
      Wistar-Kyoto rats (WKY) after chronic administration of amlodipine. Amlodipine
      treatment (10 mg/kg/day orally) significantly reduced the increase in blood
      pressure (BP) in SHR, but did not change BP in WKY. It more potently decreased
      the contractile response induced by Bay K 8644 in SHR than in WKY aorta. In both
      SHR and WKY arteries, the functional effect of chronic amlodipine treatment was
      related to occupation of the specific dihydropyridine binding sites similar to
      that which occurs after in vitro exposure to amlodipine 5 nM. Resting membrane
      potential (RMP) of aortic smooth muscle cells (SMC) from SHR was depolarized by
      12 mV as compared with SMC from WKY, indicating that the higher potency of
      amlodipine in arteries from SHR could be related to the depolarization-induced
      increase in affinity for amlodipine of Ca2+ channels in SHR.

PMID- 7528835
TI  - Effects of E-4031 on atrial fibrillation threshold in guinea pig atria:
      comparative study with class I antiarrhythmic drugs.
AB  - The effects of E-4031, a new class III antiarrhythmic agent, on atrial
      fibrillation threshold (AFT), atrial effective refractory period (ERP), and
      interatrial conduction time (ACT) were investigated in Langendorff-perfused
      guinea pig hearts; the results were then compared with those of the class I
      agents disopyramide, procainamide, lidocaine, and flecainide. Whole guinea pig
      hearts were perfused with Tyrode's solution containing acetylcholine (ACh 3 x 10(
      7) M). The three indexes were measured before and after administration of the
      test drugs, using right atrial extrastimulus and 50-Hz continuous stimulation.
      Disopyramide, procainamide, and flecainide (> or = 10(-6) M) significantly
      increased AFT. Although E-4031 (> or = 3 x 10(-6) M) also increased AFT, this
      effect was less potent than that observed with the other drugs. E-4031 (> or =
      10(-6) M) significantly prolonged ERP, and this prolongation was less pronounced
      than that observed with disopyramide but similar to that observed with
      procainamide or flecainide. E-4031 did not affect ACT, and the greatest
      prolongation of ACT was observed with flecainide. Lidocaine had no effect on any
      of the indexes. These findings suggest that in guinea pig hearts E-4031 exerts an
      antifibrillatory effect by prolonging atrial ERP alone, but this effect is less
      pronounced than that observed with class I drugs, because AFT measured by 50-Hz
      continuous stimulation is influenced by both ERP and ACT.

PMID- 7528836
TI  - Interactions of blockade of nitric oxide synthase and angiotensin-converting
      enzyme on renal function in conscious rabbits.
AB  - We tested the effects and interactions of blockade of nitric oxide (NO) synthase
      and angiotensin-converting enzyme (ACE) on renal function. Six rabbits were
      studied four times, each at 14-day intervals. The treatments were intravenous
      (i.v.) vehicle, NG-nitro-L-arginine (L-NNA) 5 mg/kg, captopril 500 micrograms
      plus 3.3 micrograms/kg/min, or L-NNA plus captopril. The studies were performed
      in random order. Arterial blood pressure (BP), heart rate (HR), and clearance of
      H2O, Na+, Li+, [3H]inulin [glomerular filtration rate (GRF)], and
      paraaminohippuric acid (PAH, renal plasma flow) were measured for the hour before
      treatment and for 3 h after treatment. Renal blood flow (RBF), renal vascular
      conductance, and GFR were reduced by 36 +/- 4, 41 +/- 4, and 17 +/- 5%,
      respectively, after L-NNA treatment. Although captopril did not affect these
      variables significantly when given alone, it completely abolished the effects of
      L-NNA. After L-NNA administration, sodium excretion decreased by 41 +/- 11%,
      chiefly attributable to reduced GFR, although increased reabsorption of sodium
      also contributed. The site of this increased reabsorption was probably the
      proximal nephron, since Li+ reabsorption (a marker of proximal tubular sodium
      reabsorption) tended to increase by 8.4 +/- 4.8%. Captopril had a natriuretic
      effect chiefly attributable to reduced sodium reabsorption in the proximal
      nephron. When these agents were coadministered, proximal tubular sodium
      reabsorption did not change significantly. Our data suggest the existence of a
      functional interaction between ACE and NO synthase in control of RBF and
      GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528837
TI  - Inhibition of EDRF release by native low-density lipoprotein from cultured
      porcine endothelial cells through intracellular mechanisms.
AB  - Cyclic GMP accumulation in endothelial cells-smooth muscle cells (EC-SMC)
      coculture induced by both receptor-dependent (thrombin, bradykinin, BK) and
      receptor-independent (Ca(2+)-ionophore A23187) stimulation, was inhibited by
      preincubation with low-density lipoprotein (LDL) in time- and concentration
      dependent manner. At least 5 min was necessary for the complete blockade with LDL
      (protein 1 mg/ml). LDL did not affect cyclic GMP-increase by sodium nitroprusside
      (SNP), a direct stimulator of SMC, but oxidized (ox)LDL (50-250 micrograms/ml)
      markedly reduced it. An increase of cyclic GMP accumulation in SMC by eluate from
      stimulated EC columns was completely blocked by 10-min pre-incubation of the
      column with LDL with or without superoxide dismutase (SOD). In contrast,
      preincubation of the SMC dish with LDL did not affect cyclic GMP accumulation by
      the eluate from the stimulated EC column, but preincubation with oxLDL (protein
      50-100 micrograms/ml) greatly reduced it. Exposure time of released EDRF to LDL
      in both coculture and column experiments was < 40-45 s. These results suggest
      that a brief exposure of EC to pathophysiologic concentration of LDL exclusively
      affects EC functions, attenuating endothelium-derived relaxing factor (EDRF)
      release through intracellular mechanisms, and consumption of released EDRF by LDL
      does not appear to be involved in this LDL inhibitory effect. Possible inhibitory
      mechanisms of LDL are discussed.

PMID- 7528838
TI  - Electrophysiologic effects of detajmium on isolated dog cardiac ventricular and
      Purkinje fibers.
AB  - We studied the electrophysiologic effects of the antiarrhythmic compound
      detajmium (Tachmalcor) on isolated dog and rabbit cardiac preparations, applying
      the conventional intracellular microelectrode techniques. In dog ventricular
      muscle fibers (37 degrees C, stimulation frequency 1 Hz), 1 microM detajmium did
      not change resting potential (RP), action potential amplitude (APA), AP duration
      measured at 90% of repolarization (APD90), or effective refractory period (ERP)
      significantly, but reduced maximum rate of depolarization (Vmax) significantly
      from 236.7 +/- 28.9 to 177.3 +/- 22.5 V/s (n = 6, p < 0.01). In dog Purkinje
      fibers (37 degrees C, stimulation frequency 1 Hz), 1 microM detajmium
      significantly decreased APA from 111.1 +/- 12.3 to 100.0 +/- 2.5 mV (n = 8, p <
      0.003), APD90 from 359.0 +/- 17.5 to 262.1 +/- 12.3 ms (n = 8, p < 0.001) and
      Vmax from 687.5 +/- 57.2 to 523.7 +/- 58.2 V/s (n = 8, p < 0.001) without
      changing maximal diastolic potential or ERP/APD ratio significantly. The effect
      of detajmium on Vmax in both dog ventricular muscle and Purkinje fibers was
      frequency dependent. Fractional Vmax block was 0.185 +/- 0.008 1/AP. The recovery
      kinetics of Vmax (offset kinetics) was extremely slow (time constant = 348.16 +/-
      57.43 s) considerably slower than most of those of other antiarrhythmic drugs yet
      reported. Detajmium in concentration < 32 microM did not influence the beta
      adrenoceptors or slow response APs in dog ventricular tissue significantly. On
      the basis of its electrophysiologic effects, detajmium, like prajmaline,
      encainide, or flecainide, can be best classified as a class I/C antiarrhythmic
      drug according to the Vaughan Williams' classification scheme.

PMID- 7528839
TI  - Differential effects of the new class III agent dofetilide on potassium currents
      in guinea pig cardiomyocytes.
AB  - The electrophysiologic effects of dofetilide (UK 68,798), a new class III
      antiarrhythmic drug were investigated on the following currents in guinea pig
      left ventricular cardiomyocytes by whole-cell patch-clamp technique: (a) delayed
      rectifier potassium current with its fast component (IKr) and its slow component
      (IKs), (b) inward rectifier potassium current (IK1), (c) fast sodium current
      (INa), and (d) L-type calcium current (ICa). Dofetilide in 10(-6) M reduced the
      amplitude of IKr to 61% of control currents, as measured by 200-ms test pulses
      and analysis of the deactivating tail currents of IKr. On the deactivating tail
      currents of IKs, dofetilide caused no significant amplitude change, but time
      constants of deactivation became 2.3 times slower, as measured by 2,000-ms test
      pulses and analysis of the deactivating tail currents of IKs. When the
      concentration of dofetilide was increased, these effects were more pronounced.
      Rapid application of the substance to the cells showed that IKr was reduced in
      the first minute to 60% of control currents. For complete current suppression, at
      least 3 min were necessary. The suppression effect remained unchanged during a 10
      min washout phase. Dofetilide had no effect on IK1. Neither were amplitudes and
      Hodgkin-Huxley parameters of sodium current influenced by dofetilide. Calcium
      currents were not blocked by dofetilide. Dofetilide is not only a highly
      selective blocker of IKr, but also delays deactivation of IKs.

PMID- 7528840
TI  - Comparison of effects of angiotensin-converting enzyme inhibition with those of
      angiotensin II receptor antagonism on functional and metabolic recovery in
      postischemic working rat heart as studied by [31P] nuclear magnetic resonance.
AB  - To assess the role of angiotensin II (AII) in development of myocardial injury
      during ischemia and reperfusion, the effects of short-term treatment with the
      angiotensin-converting enzyme (ACE) inhibitor lisinopril were compared with the
      effects of short-term treatment with L-158,338, an AII antagonist, in isolated
      working rat heart. Myocardial function was assessed and correlated with
      simultaneous measurement of high-energy phosphate metabolism and intracellular pH
      by [31P] nuclear magnetic resonance (NMR) before, during, and after global
      ischemia. Hearts from rats treated with 1 mg/kg lisinopril in vivo recovered
      substantially more function than those of controls (p < 0.001), whereas 50 ng/ml
      (0.11 microM) lisinopril in vitro had no effect on functional recovery. A dose
      dependent increase in functional recovery was observed in rat heart treated with
      0.3, 1, or 3 mg/kg L-158,338 in vivo (p < 0.005). Treatment with 50 ng/ml (0.12
      microM) L-158,338 in vitro also resulted in increased functional recovery (p <
      0.02). Significantly milder acidosis during ischemia and significantly increased
      coronary flow were characteristic of the improved functional recovery exhibited
      by the groups treated with either lisinopril or L-158,338 in vivo. Treatment with
      L-158,338 in vitro caused significantly increased coronary flow during
      reperfusion as compared with either its control group or with lisinopril
      treatment in vitro. High-energy phosphate metabolism was essentially unchanged by
      any treatment regimen. AII antagonism alone resulted in a degree of improvement
      in functional recovery comparable to that observed with oral ACE inhibitor
      treatment.

PMID- 7528841
TI  - Dual cardiovascular effects of endothelin-1 dissociated by BQ-153, a novel ETA
      receptor antagonist.
AB  - Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide that
      elicited both vasodilator and vasoconstrictor responses in anesthetized pigs.
      Within 1.0 min after the first injection of ET-1 (0.4 nmol/kg, intravenously,
      i.v.) there was a transient decrease in mean arterial pressure (MAP 82 +/- 4 to
      64 +/- 5 mm Hg; p < or = 0.01). The vasodepressor response was accompanied by
      reductions in left ventricular (LV) + dp/dtmax (1,834 +/- 104 to 1,493 +/- 87 mm
      Hg/s, p < or = 0.001), LV - dp/dt (2,600 +/- 149 to 1,865 +/- 136 mm Hg/s; p < or
      = 0.001) and cardiac output (CO 2.6 +/- 0.1 to 2.0 +/- 0.1 L/min, p < or =
      0.001). The short (< 3.0 min) vasodilatory phase was followed by a prolonged (>
      15 min) vasopressor response in which MAP (82 +/- 4 to 103 +/- 5 mm Hg; p < or =
      0.001) and pulmonary arterial pressure (PAP 11 +/- 1 to 15 +/- 1 mm Hg; p < or =
      0.01) increased. With each subsequent dose (0.4 nmol/kg i.v.) of ET-1, the
      initial vasodilatory component diminished progressively, only a monophasic
      vasoconstrictor response was observed after the fourth dose. The reductions in CO
      progressively decreased from 2.6 to 0.1 to 1.7 +/- 0.1 L/min (p < or = 0.001) by
      the end of the experiment. In contrast to the systemic circulation effects, ET-1
      produced consistent and reproducible reductions in renal blood flow (RBF 105 +/-
      16 to 21 +/- 6 mm Hg; p < or = 0.004) that lasted approximately 30 min.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7528842
TI  - Influence of oxygen on endothelium-derived relaxing factor/nitric oxide and K(+)
      dependent regulation of vascular tone.
AB  - We investigated the effect of hypoxia on acetylcholine (ACh) stimulated,
      endothelium-derived relaxing factor/nitric oxide (EDRF/NO)-dependent relaxation,
      and on basal tension in rat aortic rings. ACh (10(-9)-10(-6) M)-mediated
      relaxation at high [95%, Emax -76.2 +/- 4.5% of phenylephrine (PE)-induced
      constriction] and normal (20%, Emax -81.2 +/- 3.6%) O2 levels was inhibited by
      hypoxia (5%, Emax -36.2 +/- 7.2%); residual hypoxic relaxation was blocked by the
      K+ channel antagonist glibenclamide. To address whether O2 influenced EDRF/NO and
      K+ channel contributions to basal tone, the effect of stepwise reduction of
      available O2 (95, 20, 5, and 0%) was studied in intact and endothelial cell (EC)
      denuded rings. The effects in these rings were compared with results of the same
      progressive reduction in O2 in the presence of the NO-synthase inhibitor N omega
      nitro-L-arginine methyl ester (L-NAME) (10(-4) M) or glibenclamide (10(-4) M). EC
      intact and EC-denuded rings constricted to 0.80 +/- 0.10 and 1.41 +/- 0.15 g,
      respectively. Reducing O2 to 20% had no significant effect on vascular tension,
      but 5% caused constriction (p < 0.05) in EC-intact rings (0.90 +/- 0.15 g). This
      hypoxic vasoconstriction was blocked by L-NAME, but not by glibenclamide,
      suggesting that hypoxic vasoconstriction was mediated by withdrawal of EDRF/NO.
      In contrast, EC-denuded rings showed a significant relaxant response at 5% O2.
      When O2 was then reduced further (95% N2/5% CO2), both EC-intact and EC-denuded
      rings relaxed, and this relaxation reached baseline tension (0.10 +/- 0.1
      g).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528844
TI  - Calcium sensitization as a positive inotropic mechanism in diseased rat and human
      heart.
AB  - The two isomers of the positive inotropic compound EMD 53998, (+)EMD 57033 and (
      )EMD 57439, possess selective calcium sensitizing and phosphodiesterase (PDE)
      inhibitory properties, respectively. We measured the pharmacological responses to
      both enantiomers in isolated rat cardiac and vascular tissues and in muscles from
      severely failing human hearts. We also measured positive inotropic and
      chronotropic responses to EMD 57033 in cardiac tissues from rats with thyroid
      dysfunction, diabetes, or hypertension. Both compounds increased force of
      contraction in isolated rat cardiac tissues, although the ventricular response to
      EMD 57439 was only approximately 10% that of calcium chloride. Forskolin
      pretreatment potentiated responses to both compounds in atria but only to EMD
      57439 in ventricles. Hyperthyroidism increased ventricular responses to EMD 57033
      relative to calcium chloride; hypothyroidism and diabetes decreased these
      responses. Ventricular responses were unchanged in hypertensive rats. Both
      enantiomers produced positive inotropy in human isolated right atrial trabeculae,
      although the maximal increases were only 14% (EMD 57033) and 26% (EMD 57439) that
      of calcium chloride. In rat thoracic aortic rings, both enantiomers produced
      relaxation; the responses due to EMD 57033 were endothelium dependent. Thus,
      calcium sensitization produces positive inotropy and vascular relaxation in rats.
      Positive chronotropic responses to EMD 57033 are most likely due to PDE
      inhibition. The limited inotropic response in severely failing human myocardium,
      together with possible vasorelaxation, may provide cardiac support in heart
      failure without an excessive increase in cardiac O2 demand.

PMID- 7528843
TI  - Effects of magnesium supplementation in a porcine model of myocardial ischemia
      and reperfusion.
AB  - We tested the hypothesis that acute, intravenous (i.v.) magnesium (Mg2+)
      supplementation would protect against myocardial stunning in an in situ swine
      model of regional ischemia and reperfusion and that a concomitant inhibitory
      effect on platelet aggregation would be elicited. An open-chest model was used,
      with transient occlusion of the left anterior descending coronary artery (LAD)
      for 8 min. Regional contractile function was assessed by measuring wall
      thickening fraction with epicardial Doppler crystals. One control group (n = 6)
      and two treatment groups were studied: group I (n = 6) received 750 mg MgSO4
      before occlusion; group II (n = 6) received 1 g MgSO4 after the occlusion. Both
      protocols produced significant hypermagnesemia. In group I, platelet aggregation
      was measured before and after Mg2+ treatment using platelet-rich plasma (PRP) and
      various agonists (ADP 5 and 10 mM and collagen 1 mg/ml). As compared with
      controls, both treatment groups experienced significantly less postischemic
      dysfunction, with systolic function returning more quickly to baseline.
      Furthermore, platelet aggregation was significantly decreased immediately after
      Mg2+ infusion. Inhibition of platelet aggregation induced by Mg2+ treatment
      occurs concomitantly with significant amelioration of postischemic myocardial
      dysfunction.

PMID- 7528845
TI  - Effect of nisoldipine on contractions evoked by endothelin-1 in human isolated
      distal and proximal coronary arteries and veins.
AB  - We investigated the differences in the vasoconstrictor effect of endothelin-1 (ET
      1) on small and large human coronary arteries and veins and blockade of ET's
      action with calcium antagonists. Rings from distal and proximal human coronary
      arteries and veins were suspended in organ baths and exposed to graded
      concentrations of ET-1 (0.1-30 nM). Coronary veins were the most sensitive to the
      constrictor action of ET-1. In addition, distal coronary arteries were more
      sensitive than proximal arteries (EC50 value-log M: 8.92 +/- 0.05 and 8.34 +/-
      0.1, respectively). In proximal arteries, incubation with subthreshold
      concentrations of ET (300 pM) potentiated the vasoconstrictor effect of serotonin
      1 microM (115 +/- 2.6% over contractile level before incubation). This
      potentiated contraction was fully blocked by nisoldipine, a calcium antagonist.
      In contrast, this potentiation was not observed in human coronary veins.
      Nisoldipine partly antagonized the contraction evoked by ET-1 in human coronary
      arteries, but ET-contracted coronary veins were completely resistant to calcium
      channel blockade. Low concentrations of ET-1 approximating reported circulating
      levels result in significant contraction of human coronary veins and potentiate
      the constrictor effect of serotonin in coronary arteries. The blocking effect of
      the calcium antagonist nisoldipine varies among distal and proximal coronary
      arteries and veins, suggesting a different mechanism of contraction for ET-1
      among these vessels. Because of the suspected role of ET-1 in coronary ischemic
      syndromes, this differential sensitivity may have important therapeutic
      implications.

PMID- 7528846
TI  - Kinetic study of atrial natriuretic peptide in patients with idiopathic dilated
      cardiomyopathy: evidence for resistance to biologic effects of the hormone even
      in patients with mild myocardial involvement.
AB  - Atrial natriuretic peptide (ANP) kinetics was studied in 12 patients with
      idiopathic dilated cardiomyopathy at different sodium excretion (30-175 mmol/day)
      and variable degrees of hemodynamic dysfunction [New York Heart Association
      (NYHA) class range I-III] to investigate whether differences in renewal and
      distribution of this hormone (as compared with those of a control group) play a
      role in pathogenesis and evolution of heart failure. [125I]Labeled ANP was
      injected as a bolus, and a high-performance liquid chromatography (HPLC)
      procedure was used to purify the labeled hormone in venous plasma samples
      collected for < or = 50 min after injection; the main ANP kinetic parameters were
      then derived from the disappearance curve of the labeled hormone. As in controls,
      a positive linear regression between ANP metabolic clearance rate (MCR,
      ml/min/m2) values and daily urinary excretion of sodium (NaUE, mmol/day) was
      noted in patients. The different linear regression coefficients between normal
      subjects (MCR = 365 +/- 8.08 NaUE, r = 0.986, p < 0.0001) and patients (MCR = 497
      + 18.5 NaUE, r = 0.867, p = 0.001) indicate that in patients a higher peptide
      clearance rate is needed to obtain the same biologic effect (sodium excretion)
      and suggest that resistance to biologic effects of the hormone exists in patients
      at an early stage of disease (NYHA class I). When the efficiency of the ANP
      system in excreting sodium was expressed as the ratio of NaUE to ANP production
      rate (PR = MCR x ANP plasma concentration, microgram/day/m2) patients showed
      significantly lower values (p = 0.0126) than normal volunteers, thus confirming
      resistance to the hormone effects. Significantly lower values for ANP total
      distribution volume (16.5 +/- 8.4 L/m2), mean residence time in the sampling
      space (4.04 +/- 1.14 min), mean residence time in the body (7.25 +/- 2.13 min),
      and fewer recycles through the initial (sampling) space (0.27 +/- 0.16) were
      noted in patients, indicating an altered mechanism regulating distribution of the
      hormone. The positive correlations between ANP MCR (L/min/m2) values and cardiac
      index (CI, L/min/m2) (MCR = -1.24 + 1.17 CI, r = 0.689, p = 0.0092) and between
      initial distribution volume (IDV, L/m2) and CI (IDV = -11.2 + 6.85 CI, r = 0.730,
      p = 0.0046) in all patients indicate that hemodynamic factors contribute to the
      progressive reduction in MCR and IDV values throughout the progression of
      myocardial involvement.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7528847
TI  - Functional depression of isolated perfused rat heart mediated by activated
      leukocytes: protective effect of cloricromene.
AB  - Langendorff rat heart preparations were perfused with suspensions of human
      leukocytes containing approximately 65% polymorphonuclear cells (PMN). The cells
      were either unstimulated or activated with 1.6 x 10(-8) phorbol 12-myristate 13
      acetate (PMA). Left ventricular developed pressure (LVDP), coronary flow (CF),
      and heart rate (HR) were recorded during PMN infusion (10 min) and for the
      recovery period (30 min). PMN were also pretreated with cloricromene (CLO 10-50
      microM), a drug that inhibits platelet aggregation and PMN adhesion to
      endothelial cells (EC). Infusion of unstimulated cells did not affect cardiac
      function. Infusion of activated cells caused CF reduction (-44 +/- 4% at end of
      infusion; -24 +/- 4% at end of recovery, expressed as percentage of variation vs.
      basal value), LVDP decrease (-44 +/- 5% at end of infusion, -26 +/- 6% at end of
      recovery) endothelial damage, and leukocyte accumulation in heart as compared
      with hearts infused with unstimulated PMN and sham hearts. PMN accumulation was
      quantified as myeloperoxidase (MPO) activity (260 +/- 35, 39 +/- 6, 19 +/- 1 U/g,
      respectively). Superoxide dismutase (SOD 600 U/ml), catalase (2,200 U/ml),
      thiourea (10 mM) added to PMN suspension blunted CF decrease but not LVDP
      reduction and MPO increase. CLO (25-50 microM) pretreatment inhibited PMN
      accumulation, LVDP, and CF reduction by approximately 50%. These data suggest a
      role of leukocyte activation in the genesis of heart damage and raise the
      possibility of a pharmacologic intervention with drugs such as CLO that can
      interfere with this process.

PMID- 7528848
TI  - Vascular effects of pentoxifylline in humans.
AB  - In this study, we investigated the vasoactive effects of the alkylxanthine
      pentoxifylline and its interaction with the nucleoside adenosine in the forearm
      skeletal muscle vascular bed of 18 normotensive healthy volunteers.
      Pentoxifylline infusion into the brachial artery in dosages of 100, 300, and
      1,000 micrograms/100 ml forearm volume (FAV)/min, induced increments of forearm
      blood flow (FBF) of 41 +/- 6, 125 +/- 22, and 295 +/- 57%, respectively (n = 12).
      Calculated forearm vascular resistance (FVR) showed a dose-dependent decrease
      during pentoxifylline infusion. Concomitant administration of caffeine (100
      micrograms/100 ml/min), an adenosine antagonist, did not attenuate the
      vasodilator response to pentoxifylline (n = 6). Intraarterial (i.a.) infusion of
      adenosine alone (0.75, 1.5, 3.0, and 4.5 micrograms/100 ml/min) induced a dose
      dependent forearm vasodilator response. Concomitant infusion of pentoxifylline
      (100 micrograms/100 ml/min) did not cause a convincing potentiation of the
      forearm vasodilator effect of adenosine. This study demonstrates that
      pentoxifylline induces vasodilation in human forearm skeletal muscle vascular bed
      of healthy young volunteers. This vasodilator response occurred at concentrations
      that are probably much higher than those achieved with oral treatment with
      pentoxifylline. Our data further suggest that pentoxifylline-induced vasodilation
      is not mediated by adenosine receptor stimulation, but may result from inhibition
      of the enzyme phosphodiesterase (PDE).

PMID- 7528849
TI  - Human recombinant extracellular-superoxide dismutase type C improves cardioplegic
      protection against ischemia/reperfusion injury in isolated rat heart.
AB  - The cardioprotective effects of human recombinant extracellular-superoxide
      dismutase type C (hr-EC-SOD C) were compared with those of bovine Cu,Zn-SOD in
      isolated working rat heart subjected to 35-min global normothermic ischemia
      followed by 55-min reperfusion. hr-EC-SOD C or bovine Cu,Zn-SOD (3 x 10(4) and 6
      x 10(4) IU/L, respectively) was added to St. Thomas' Hospital (STH) cardioplegic
      solution infused 5 min before and 10 min after the ischemic period. Control
      hearts were treated with STH cardioplegic solution without SOD. By the end of
      reperfusion, hr-EC-SOD C-treated hearts recovered left ventricular systolic
      pressure (LVSP), aortic flow (AF) and cardiac output (CO) to 95 +/- 4, 60 +/- 4,
      69 +/- 6% of preischemic value, respectively, as compared with 86 +/- 3, 44 +/-
      5, and 52 +/- 6% in the control (p < 0.05). Cardioplegia with hr-EC-SOD C
      significantly reduced lactate dehydrogenase (LDH) release into myocardial
      effluent during reperfusion (p < 0.05) and increased ATP, AMP, and total creatine
      (Cr) tissue contents in reperfused hearts (by 21 +/- 3, 42 +/- 4, and 34 +/- 3%,
      respectively, as compared with control hearts, p < 0.05). The effects of bovine
      SOD on functional and biochemical indexes were similar but not statistically
      significant as compared with control. Treatment with hr-EC-SOD C, but not with
      bovine SOD, resulted in reduction in hydroxyl radical formation assessed by 5-5
      dimethy-1-pyrroline-N-oxide spin trap (DMPO) in coronary effluent at early
      reperfusion with electron spin resonance (ESR) technique. The results suggest
      that enhanced myocardial protection against ischemia/reperfusion injury afforded
      by hr-EC-SOD C is related to scavenging of oxygen-derived free radicals.

PMID- 7528850
TI  - Efficacy of ajmaline and propafenone in patients with accessory pathways: a
      prospective randomized study.
AB  - In a prospective randomized study, we assessed the electrophysiologic effects and
      the efficacy of ajmaline versus propafenone in patients with accessory pathways
      (APs). During initiated atrioventricular (AV) reentrant tachycardia or atrial
      fibrillation (AF), ajmaline (1 mg/kg as bolus followed by infusion of 15
      micrograms/kg/min) or propafenone (2 mg/kg, followed by infusion of 30
      micrograms/kg/min.) were randomly administered intravenously (i.v.) in 40
      patients with APs. AV reentrant tachycardia terminated in 15 of 16 patients (94%)
      on ajmaline and in 12 of 15 patients (80%, NS) on propafenone. AF ceased in 4 of
      4 patients receiving ajmaline and in 3 of 5 patients receiving propafenone
      (n.s.). During continuous infusion of drugs, AV reentrant tachycardia became
      noninducible in 10 (50%) patients receiving ajmaline, as compared with 6 (32%)
      receiving propafenone (NS). Both drugs significantly prolonged the anterograde
      and retrograde effective refractory periods (ERPs) of the AP. There were no
      significant differences in changes in electrophysiologic parameters between the
      two drugs. Ajmaline and propafenone are highly effective and safe in terminating
      and preventing reinitiation of AV reentrant tachycardia or AF in patients with
      APs. Both drugs significantly prolonged the anterograde and retrograde ERPs of
      the APs.

PMID- 7528852
TI  - Inhibitors of Ca2+ ATPase pump of sarcoplasmic reticulum attenuate reperfusion
      stunning in isolated rat heart.
AB  - We tested for the first time the hypothesis that lessened uptake of Ca2+ into
      sarcoplasmic reticulum by inhibitors of the Ca(2+)-ATPase pump can decrease the
      severity of reperfusion stunning (postischemic mechanical dysfunction). We used
      two novel inhibitors of the Ca(2+)-ATPase pump: (a) cyclopiazonic acid (CPA, 10(
      6)-10(-8)M), and (b) thapsigargin (10(-6) or 2.5 x 10(-8)M). The isolated working
      rat heart was subjected to 20-min global ischemia before 20-min reperfusion. The
      inhibitor was added either before onset of ischemia or at time of reperfusion.
      Reperfusion mechanical function (aortic output, AO) was measured and compared
      with the preischemia values. Pretreatment with CPA improved recovery of AO after
      20-min reperfusion from 78.2 +/- 3.0 (n = 12) to 93.3 +/- 1.6% (n = 7) (p <
      0.002) while CPA added during reperfusion only, improved AO recovery from 78.2 +/
      3.0 (n = 12) to 90.2 +/- 2.7% (n = 6) (p < 0.05). Pretreatment with thapsigargin
      (2.5 x 10(-8) M) improved reperfusion AO recovery from 63.5 +/- 1.1 (n = 6) to
      96.8 +/- 4.2% (n = 6) (p < 0.002), but when thapsigargin was added only during
      reperfusion AO recovery did not change. We conclude that inhibition of the Ca2+
      uptake pump represents a new principle of control of cell calcium fluxes and that
      CPA is more effective than thapsigargin. The proposed mechanism of protection
      against stunning may include inhibition of oscillations of intracellular calcium,
      and/or depletion of calcium in sarcoplasmic reticulum (SR).

PMID- 7528851
TI  - Antiatherosclerotic effects of the angiotensin-converting enzyme inhibitors
      captopril and fosinopril in hypercholesterolemic minipigs.
AB  - We evaluated the two angiotensin-converting enzyme (ACE) inhibitors captopril and
      fosinopril with regard to possible antiatherosclerotic effects in minipigs.
      Experimental hypercholesterolemia and atherosclerosis was produced in 33 minipigs
      of the Gottingen strain by an egg yolk/cholesterol-enriched diet for 1 year. One
      group (n = 11) was fed the atherogenic diet alone and served as a control. A
      second group (n = 11) received captopril (80 mg/kg/day) added to the atherogenic
      diet, and a third group (n = 11) was treated in the same manner but with
      fosinopril (8 mg/kg/day). The drug treatments produced significant reduction in
      serum ACE activity associated with a reactive increase in plasma renin activity
      (PRA), but had only minor effects on plasma lipids and lipoproteins. At the end
      of the treatment period, all animals were killed and examined for degree of
      atherosclerosis. The percentage of atherosclerotic area in the abdominal aorta
      was significantly lower in both drug-treated groups as compared with controls.
      Furthermore, accumulation of cholesterol in the thoracic and abdominal aorta was
      inhibited by drug treatment. Finally, the percentage of intimal thickening in
      abdominal aorta was significantly reduced in the drug-treated groups. In
      conclusion, the ACE inhibitors captopril and fosinopril inhibited development of
      atherosclerosis in hypercholesterolemic minipigs.

PMID- 7528853
TI  - Chromolymphography, lymph node surgery and detection of lymph node metastases:
      current state and future.

PMID- 7528855
TI  - Fludarabine + Ara-C + G-CSF: cytotoxic effect and induction of apoptosis on fresh
      acute myeloid leukemia cells.
AB  - It has been reported that the adenine nucleoside analogue fludarabine is able to
      increase the phosphorylation and the cytotoxicity of cytosine arabinoside (Ara-C)
      in different leukemic models, both in vitro and in vivo. In poor prognosis acute
      myeloid leukemia (AML), the combination of fludarabine with Ara-C and granulocyte
      colony-stimulating factor (G-CSF) has proven to be a highly effective regimen. In
      this study we aimed to further investigate the effects of this drug combination.
      In vitro, on fresh AML cells from ten patients, our results confirm an additive
      cytotoxic effect displayed by fludarabine + Ara-C, as demonstrated by isobologram
      analysis of the data. The addition of G-CSF significantly increased the efficacy
      of the drug combination. These effects appeared to be related to an increased
      incorporation of [3H]Ara-C into cellular DNA in the presence of fludarabine + G
      CSF. Furthermore, the quantitative evaluation of programmed cell death
      (apoptosis) showed that fludarabine + Ara-C + G-CSF induce apoptosis to a higher
      degree than either compound alone. This finding suggests that cooperative
      induction of apoptosis could be the potential mechanism of action of this drug
      combination.

PMID- 7528854
TI  - The application of hematopoietic growth factors in drug-induced agranulocytosis:
      a review of 70 cases.
AB  - Since 1989, granulocyte-macrophage and granulocyte colony-stimulating factors (GM
      CSF, G-CSF) have been increasingly applied in the treatment of drug-induced
      agranulocytosis. In order to evaluate the effectiveness of GM-CSF and G-CSF in
      the treatment of drug-induced agranulocytosis, we have studied all reported cases
      (n = 70) treated with GM-CSF and G-CSF, including ten patients treated during the
      last 2 years in The Netherlands. The results demonstrate that patients with a
      severe granulocytopenia (< 0.1 x 10(9)/l) treated with hematopoietic growth
      factors had a significantly faster recovery of the peripheral blood granulocytes
      compared to previous published studies. At the same time, a significantly lower
      mortality rate was observed. In patients with a severe granulocytopenia treated
      with GM-CSF or G-CSF a mortality rate of 5% was noted. No difference in
      granulocyte recovery was observed in patients treated with GM-CSF or G-CSF. The
      results of this review indicate that G-CSF and GM-CSF enhance the recovery of the
      myeloid lineage, resulting in a faster normalization of the peripheral blood
      granulocyte count and a reduced incidence of fatal complications.

PMID- 7528858
TI  - Increased sensitivity to a vitamin D3 analog in HL-60 myeloid leukemic cells
      resistant to all-trans retinoic acid.
AB  - All-trans retinoic acid (ATRA) has been demonstrated to induce the in vitro
      differentiation of human myeloid leukemic cells by several investigators. In
      addition, ATRA has been reported to induce complete remission in patients with
      acute promyelocytic leukemia. However, the majority of the patients relapse after
      several months of ATRA therapy. Since one possible cause of relapse in these
      patients is drug resistance, it is of interest to investigate the antileukemic
      activity of other agents that can be used in combination with ATRA in order to
      overcome this problem. Vitamin D3 analogs such as 1,25-dihydroxy-delta 16-23-yne
      cholecalciferol (16-23-D3) are also capable of inducing differentiation of
      myeloid leukemic cells. In this study we have isolated a clone of HL-60 leukemic
      cells that is resistant to ATRA. We have observed that the resistant cell line
      (HL-60/RA) was more sensitive to the antileukemic action of 16-23-D3 than the
      parental cell line with respect to the inhibition of cell growth and DNA
      synthesis, the induction of differentiation and the loss of cell clonogenicity.

PMID- 7528857
TI  - Characterization of the adherence of normal and leukemic CD34+ cells to
      endothelial monolayers.
AB  - The capacity of normal CD34+ marrow cells and CD34+ leukemic cell lines to adhere
      to human umbilical vein endothelial cells has been examined. Such interactions
      have importance since the processes of homing and egress within the marrow
      microenvironment involve the traverse of sinusoidal endothelium. Umbilical vein
      endothelial monolayers expressed CD44 and CD54 constitutively, and expression of
      both E-selectin (ELAM) and vascular cell adhesion molecule-1 (VCAM-1) were
      inducible with interleukin-1 (IL-1) alpha and beta and tumor necrosis factor
      (TNF). CD34+ marrow cells bound to unstimulated endothelial layers (33 vs. 16% to
      plastic), and their adhesion was significantly increased in the presence of IL-1
      or TNF. This increased adhesion was not inhibited by functionally blocking
      antibodies to E-selectin or to CD54 but was partially inhibited by antibodies to
      VCAM. CD34+ KG1a cells also bound to endothelial monolayers (33 vs. 8% to
      plastic), and such adhesion was also upregulated by pretreatment of the
      endothelial cells with IL-1 or TNF. In contrast to normal CD34+ cells, this
      increased adhesion was inhibited by antibodies to E-selectin but not to VCAM.
      These findings indicate that adhesion of both normal CD34+ cells and leukemic
      blasts to endothelial cells can be upregulated by inflammatory mediators such as
      TNF and IL-1.

PMID- 7528859
TI  - All-trans retinoic acid potentiates megakaryocyte colony formation: in vitro and
      in vivo effects after administration to acute promyelocytic leukemia patients.
AB  - In this study, we evaluated the in vitro growth of normal hematopoietic
      progenitors (CFU-GM, BFU-E, CFU-GEMM, CFU-meg) stimulated by optimal sources of
      colony stimulating activity in the absence or presence of 10(-6) M all-trans
      retinoic acid (ATRA). ATRA alone did not show any colony-stimulating ability when
      added in culture to partially purified bone marrow populations. On the other
      hand, it significantly increased the number of CFU-GM (p = 0.003) and both the
      number (p = 0.009) and size (p = 0.002) of CFU-meg in the presence of appropriate
      colony-stimulating activity. Since ATRA had only modest stimulatory effects on
      purified CD34+ cells, the megakaryocyte colony-stimulating activity of ATRA was
      mainly due to an increased production of endogenous cytokines by bone marrow
      accessory cells. In parallel experiments, the in vitro growth of the different
      hematopoietic progenitors was evaluated in 28 patients affected by acute non
      lymphoid leukemia (ANLL), mainly acute promyelocytic leukemia (APL). Bone marrow
      cells were harvested after remission induction obtained: (i) in ten APL patients
      treated with ATRA followed by one chemotherapy cycle (CHT) (3/7: Daunorubicin+Ara
      C): group A ('ATRA/CHT'); (ii) eight APL patients treated with one CHT cycle
      alone (3/7 as above): group B ('APL-CHT'); (iii) in ten ANLL-non-APL patients
      after one CHT cycle (3/7 as above): group C ('ANLL-CHT'). The number of the
      different hematopoietic progenitors, and in particular CFU-GM and CFU-meg, was
      significantly higher in APL patients treated with ATRA plus CHT (group A)
      compared to APL (group B) or ANLL-non-APL (group C) patients treated with CHT
      alone (CFU-GM: p = 0.01; CFU-meg: p = 0.03). Our data demonstrate that ATRA is
      able to potentiate both normal and APL megakaryocytopoiesis and suggest that the
      in vivo administration of ATRA could be beneficial in other pathological
      conditions, where the megakaryocyte progenitor cell compartment is impaired.

PMID- 7528856
TI  - Expression and regulation of CD30 ligand and CD30 in human leukemia-lymphoma cell
      lines.
AB  - The CD30 antigen was originally described as a specific surface marker for
      Hodgkin's lymphoma. Recent work established CD30 as a member of the tumor
      necrosis factor/nerve growth factor receptor superfamily whose ligand (CD30L) has
      also been cloned and expressed; CD30L is active as membrane-bound type II
      glycoprotein. Here, CD30L mRNA expression was studied in a panel of 102
      continuous human leukemia-lymphoma cell lines and was found only in four Burkitt
      lymphoma, one Burkit-type acute lymphoblastic leukemia and one non-Hodgkin's
      lymphoma (NHL) cell line. The product of CD30L mRNA is expressed as a membrane
      protein on the surface of these malignant B-cell lines. Treatment of these cell
      lines with soluble CD27L, phorbol ester or staphylococcus aureus Cowan antigen
      resulted in the enhancement of cell surface CD30L protein expression. CD30L mRNA
      was not detected in normal unstimulated peripheral blood (PB) monocytes, monocyte
      derived macrophages, or T-cells, but was detected in primary granulocytes;
      exposure to activating reagents induced and upregulated CD30L transcription in
      these different PB populations. While CD40 and CD30L surface protein expression
      on PB monocytes could be enhanced or induced by treatment with gamma-interferon,
      these cells remained negative for CD30, both at the mRNA and at the protein
      level. Similarly, PB monocyte-derived macrophages and granulocytes remained
      negative for CD30 mRNA and protein expression, regardless of stimulation. Only
      activated T-cells expressed CD30 mRNA and surface protein. CD30L-transfected
      cells and cells constitutively expressing CD30L delivered a similar stimulus for
      proliferation of the CD30+ Hodgkin's disease (HD)-derived cell line HDLM-2, but
      inhibited proliferation of the CD30+ large cell anaplastic lymphoma cell line
      KARPAS-299. These data provide strong evidence for the involvement in growth
      regulation of recombinant and natural CD30L through its interaction with the CD30
      receptor. Collectively, these data suggest that the CD30L-CD30 interaction has
      potent biological activity and might play a critical role in the immune response
      and pathogenesis of HD and some NHL, in particular Burkitt lymphomas.

PMID- 7528860
TI  - Effect of ubenimex on the proliferation and differentiation of U937 human
      histiocytic lymphoma cells.
AB  - We investigated the effect of ubenimex on the growth and differentiation of U937
      cells, a histiocytic lymphoma cell line. Ubenimex is a dipeptide ((2S,3R)-3-amino
      2-hydroxy-4-phenylbutyryl-L-leucine) and an inhibitor of aminopeptidase B
      produced by Streptomyces olivoreticuli. Ubenimex inhibited the proliferation of
      U937 cells in a dose-dependent manner. Ubenimex-treated U937 cells showed
      condensation of nuclear chromatin, increase of cytoplasmic vacuoles and more
      intense nonspecific esterase staining compared with untreated U937 cells.
      Expression of CD13 and CD68 detected by monoclonal antibodies My7 and EBM11,
      respectively, was enhanced by ubenimex, but the expression of CD4 detected by
      MT310 was significantly decreased. The effects of ubenimex on U937 cell growth
      inhibition and enhancement of monocytic cell surface marker expression on U937
      cells were reversible when cultivated without ubenimex for more than 6 days. In
      addition, the bactericidal activity of U937 cells was increased by ubenimex
      treatment, and was further enhanced by treatment with macrophage colony
      stimulating factor (M-CSF). Furthermore, ubenimex augmented the expression of M
      CSF receptors by U937 cells and enhanced the tyrosine kinase activity of cellular
      pp60c-src. These findings indicated that ubenimex inhibited the proliferation of
      U937 cells and induced morphological, cytochemical and functional differentiation
      into monocyte/macrophages.

PMID- 7528861
TI  - Primitive multilineage progenitor cells predominate in peripheral blood early
      after mobilization with high-dose cyclophosphamide and GM-CSF or G-CSF.
AB  - The change in phenotype, number and proliferative capacity of peripheral blood
      hematopoietic progenitors (PBHP) was studied in six patients with multiple
      myeloma during hematopoietic recovery after mobilization with high-dose
      cyclophosphamide and GM-CSF or G-CSF. In all six patients the first CD34+ cells
      appearing in the peripheral blood (PB) after cytoreductive treatment were
      predominantly CD34+/33- (> 70%). At later stages when leukapheresis procedures
      were started, the CD34+/33+ cells predominated in five of six patients. In
      leukapheresis harvests of peripheral blood, and in bone marrow addition of SCF
      and IL-6 to the culturing medium enhanced the plating efficiency. In peripheral
      blood an increase from 12 to 22% for CD34+/33+ and from 6 to 14% for CD34+/33-
      was observed. In normal bone marrow we observed an increase from 15 to 23% for
      CD34+/33+ and from 7 to 17% for CD34+/33-. Highly proliferative progenitors (>500
      cells) in the CD34+/33- fraction appeared to be dependent on the addition of
      'stem cell recruiting factors' (SCF and IL-6); in bone marrow the percentage of
      wells with >500 cells increased from 0.9 to 12.6% after SCF+IL-6 and in PBHP from
      2 to 9%. We conclude that the first progenitors appearing in the peripheral blood
      after priming with high-dose cyclophosphamide and GM- or G-CSF have a more
      primitive immunophenotype, CD34+/33-.

PMID- 7528862
TI  - Characterization of a novel interleukin-6 autocrine-dependent human plasma cell
      line.
AB  - A new human monoclonal plasma cell line, designated UTMC-2, was established from
      the pleural effusion of a patient with immunoglobulin (Ig)A kappa-related
      multiple myeloma. The cultured cells were Epstein-Barr virus-negative and
      exhibited the morphological and ultrastructural features characteristic of plasma
      cells. Immunohistochemical analyses revealed the presence of cytoplasmic IgA
      kappa as well as the plasma cell-associated surface antigens CD38 and CD56. Other
      B-cell markers, including CD10, CD19, CD20, and HLA-DR, were absent. The UTMC-2
      cells were interleukin (IL)-6 responsive: Co-culture with IL-6 increased IgA
      kappa synthesis and cell proliferation in a dose-dependent manner. In contrast,
      an IL-6 antisense oligonucleotide had an opposite effect. Although the UTMC-2
      cells expressed IL-6 mRNA (as demonstrated by reverse transcriptase-polymerase
      chain reaction (RT-PCR)) and contained IL-6, the concentration of this cytokine
      in cell culture supernatants was less than that detectable by the enzyme-linked
      immunosorbent assay (ELISA) employed (i.e. <3 pg/ml). Further, cell growth was
      not inhibited by polyclonal or monoclonal anti-IL-6 antibodies. Flow cytometric
      analysis revealed that IL-6 receptors present on the surface of the UTMC-2 cells
      were not saturated with endogenous IL-6. Taken together, these results indicate
      that, in this human plasma cell line, IL-6 functions uniquely in an intracellular
      autocrine fashion to enhance Ig synthesis and cell growth. In this respect, the
      UTMC-2 cells represent a novel resource for further study of the role of IL-6 in
      the pathogenesis of multiple myeloma.

PMID- 7528863
TI  - Cancer combination chemotherapy with retinoids: experimental rationale.
AB  - Retinoids, cytokines as well as 1,25-dihydroxyvitamin D3 and its analogs are all
      classes of compounds with pleiotropic actions. They inhibit proliferation in
      human transformed epithelial cell lines and induce differentiation in human
      transformed hemopoietic cell lines. In a murine model of tumor cell-induced
      angiogenesis all three classes of compounds inhibit the formation of new blood
      vessels, necessary for supplying the growing tumor with oxygen and nutrients.
      Combinations of compounds from the three different classes lead to higher
      efficacy than the compounds administered as single agents. The effects of
      combinations vary depending on the individual representatives of the three
      classes and on the particular test models used. Additive, synergistic and
      potentiating effects have been observed. The results obtained in experimental
      systems raise hope that combination therapy might be useful in the treatment of
      certain human neoplastic diseases.

PMID- 7528864
TI  - Prostate-specific antigen (PSA): its clinical value in prostatic disease.

PMID- 7528865
TI  - Visual laser ablation of the prostate: a preliminary report.
AB  - OBJECTIVE: To report our preliminary experience with visual laser ablation of the
      prostate (VLAP) for treating bladder outlet obstruction caused by benign
      prostatic hyperplasia (BPH) and to evaluate its short-term outcome. DESIGN: We
      reviewed our laser technique in 47 men with symptomatic obstruction caused by BPH
      who underwent VLAP between July 1992 and April 1993 at our institution, and we
      compared our results with those reported in the literature. MATERIAL AND METHODS:
      Our 47 patients were from 43 to 87 years old (mean, 69.6). The mean pretreatment
      American Urological Association symptom score was 22, mean peak flow rate was 9.5
      mL/s, and mean postvoid residual urinary volume was 136 mL. Neodymium:yttrium
      aluminum-garnet laser energy was delivered at the 2-, 4-, 8-, and 10-o'clock
      positions and, when necessary, to the median lobe by one of two lateral-firing
      laser probes. All but the first four patients were treated on an outpatient
      basis, and all patients were catheterized (Foley catheter) for 2 to 10 days after
      VLAP. RESULTS: Of the 47 patients, 32 had data pertaining to a mean follow-up of
      5 months; they had a mean symptom score of 10, mean peak flow rate of 15.7 mL/s,
      and mean postvoid residual volume of 63 mL. In 12 patients, data from a mean
      follow-up of 11 months were available; they had a mean symptom score of 6, mean
      peak flow rate of 18.8 mL/s, and mean postvoid residual volume of 10 mL.
      Perioperative complications (myocardial infarction, thrombophlebitis, and
      epididymitis) in three patients responded to conservative therapy. Urinary
      retention occurred for 2 to 60 days after initial removal of the Foley catheter
      in 12 patients, who then had resumption of spontaneous voiding. In three patients
      who stated their condition was worse postoperatively, conventional transurethral
      resection of the prostate was done 6 months after VLAP, and a fourth patient had
      a persistently obstructive bladder neck incised 8 months after VLAP. CONCLUSION:
      Our early experience and that reported in the literature indicate that VLAP is a
      safe and efficacious alternative treatment of obstructive BPH. Although the early
      results of VLAP rival those of transurethral resection of the prostate, the
      success rate in treating large prostates should be improved, and long-term
      results should be assessed to determine the durability of the beneficial effects.

PMID- 7528866
TI  - Digital image analysis.

PMID- 7528867
TI  - Visual laser ablation of the prostate: a viable alternative to transurethral
      resection of the prostate.

PMID- 7528868
TI  - Developing and testing a multimedia presentation of a health-state description.
AB  - Quality-adjustment weights for health states are an essential component of cost
      utility analysis (CUA). Quality-adjustment weights are obtained by presenting
      large numbers of subjects with multiattribute descriptions of health states for
      rating. Comprehending multiattribute health states is a difficult task for most
      respondents. The authors hypothesized that multimedia (MM) presentation using
      computers might facilitate this task better than would a paper-based text (Text).
      To test this hypothesis, they developed closely matched MM and Text descriptions
      of health states in the first-person narrative style, and developed a method of
      testing the presentation of a health state. Subjects were randomized to exposure
      to either MM or Text and subject recall of the health state and recognition of
      features of the health state were tested. How well defined the preferences of the
      subjects were after each presentation method was assessed by having the subjects
      mark on a double-anchored visual-analog scale the "best" and "worst" they
      believed the quality of life in the health state might be. MM subjects had better
      recall (11.85 vs 9.44 of a total of 24 meaning units, p = 0.098) and better
      recognition (4.71 vs 4.22, p = 0.08). The average interval between the "best" and
      "worst" ratings was shorter for the MM subjects (2.19 cm vs 3.26 cm, p =
      0.12).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528869
TI  - Hypothalamic galanin-like immunoreactivity and its gene expression in relation to
      circulating corticosterone.
AB  - The neuropeptide galanin (GAL), which exists in dense concentrations within the
      hypothalamus, has physiological actions which are neuroendocrine in nature. In
      light of evidence showing GAL to alter the release of the adrenal steroid,
      corticosterone (CORT), a possible effect of this steroid on GAL gene expression
      and peptide production in discrete hypothalamic and brainstem sites was
      investigated. Using radioimmunoassay and in situ hybridization techniques, this
      peptide was examined in rats that had received SHAM surgery, adrenalectomy (ADX)
      and ADX+CORT replacement. The results showed a clear, site-specific change in GAL
      in relation to circulating CORT. A loss of CORT after ADX caused a dramatic
      decline in GAL peptide and mRNA levels in the arcuate nucleus and peptide levels
      in the median eminence, with no change occurring in other hypothalamic areas. In
      the brainstem, a similar change was detected in the dorsal raphe nucleus but not
      the locus coeruleus. The GAL peptide and mRNA levels in these specific brain
      areas of ADX rats was restored by CORT replacement, which had no impact on GAL in
      other brain sites. These findings demonstrate that CORT's impact on brain GAL is
      highly site specific, possibly determined by local concentrations of steroid
      receptors.

PMID- 7528870
TI  - 31P NMR investigation of energy metabolism in perifused MMQ cells.
AB  - The MMQ cell line is a unique prolactin-secreting rat pituitary cell line. MMQ
      cells entrapped in agarose gel threads are metabolically active, as determined by
      the uptake and phosphorylation of creatine and the maintenance of high energy
      phosphates for over 15 h. Forskolin activates the catalytic subunit of adenylyl
      cyclase and, in MMQ cells, elevates the level of cAMP and stimulates prolactin
      secretion. 31P NMR spectroscopy was used to investigate the energy metabolism of
      the MMQ cells during stimulation by forskolin. The ability to measure small
      changes in the energy status of these cells was enhanced by increasing the PCr
      levels in the cells. Administration of forskolin to the perifused MMQ cells
      resulted in acute, reversible, and dose-dependent changes in the 31P NMR spectra
      of the cells within 12 to 24 min of the beginning of forskolin exposure. Several
      lines of evidence indicate that the changes observed in the MMQ cells are the
      composite result of the interaction of forskolin with adenylyl cyclase and the
      plasma membrane glucose transporter. Also, preincubation of the MMQ cells with
      the dopamine agonist, bromocriptine, attenuates the forskolin-stimulated decrease
      in the PCr resonance by approximately 50%. This attenuation indicates that the
      forskolin-stimulated changes in energy metabolism are probably related to the
      prolactin secretion process.

PMID- 7528871
TI  - Assessing gene expression during oxidative stress.

PMID- 7528872
TI  - OxyR regulon.

PMID- 7528873
TI  - One-day northern blotting for detection of mRNA: NDGA inhibits the induction of
      MnSOD mRNA by agonists of type 1 TNF receptor.

PMID- 7528874
TI  - A review of reflex sympathetic dystrophy and related syndromes.
AB  - Reflex sympathetic dystrophy and related syndromes such as sympathetically
      maintained pain and causalgia are often confused and over-diagnosed. In an effort
      to set ground rules and recommendations on these conditions, an attempt is made
      here to explain the clinical findings and recommendations for treatment. The goal
      of this article is to aid in reduction of inappropriate diagnosis and subsequent
      inappropriate management.

PMID- 7528875
TI  - Chaperone-mediated activation in vivo of a Pseudomonas cepacia lipase.
AB  - An extracellular Pseudomonas cepacia lipase, LipA, is inactive when expressed in
      the absence of the product of the limA gene. Evidence has been presented that
      LimA is a molecular chaperone. The lipA and limA genes have been cloned in
      separate and independently inducible expression systems in Escherichia coli.
      These systems were used to test the molecular chaperone hypothesis by
      investigating whether LimA could activate presynthesized prelipase and whether
      presynthesized LimA could activate newly synthesized prelipase. The results show
      that LimA cannot activate presynthesized prelipase and that presynthesized LimA
      can activate only a limited number of de novo synthesized prelipase molecules. Co
      immunoprecipitation of prelipase/lipase with LimA generated a 1:1 complex of
      prelipase/lipase and LimA. The results suggest that a 1:1 complex of LipA and
      LimA is required for prelipase processing and secretion of active lipase.

PMID- 7528877
TI  - Molecular analysis of hypoxanthine phosphoribosyltransferase gene deletions
      induced by alpha- and X-radiation in human lymphoblastoid cells.
AB  - Mutations caused by exposure to X-radiation and to radon and its decay products
      were compared in the hprt gene of a human lymphoblastoid cell line. Thirty-one X
      radiation-induced, 29 radon-induced, and 24 spontaneous mutants were recovered
      from cell cultures under identical conditions except for the exposure to
      radiation. Seven spontaneous point mutations were recovered and DNA sequenced.
      These mutations included three C:G-->T:A transitions. These spontaneous point
      mutations were located in the exon or splice donor regions of five of the nine
      hprt exons. Four X-radiation-induced and three radon-induced point mutations were
      also analyzed by DNA sequencing. The frequency of induced mutants at the D0 doses
      for radon and X-radiation respectively were 5 x 10(-6) and 4.5 x 10(-6).
      Deletions were the predominant mutations recovered from both radon- and X
      irradiated cells. Eighty-one percent of the mutants from X-radiation-treated
      cultures, 86% of the radon-treated cultures, and 63% of the spontaneous mutants
      involved deletions. Deletions involving exon and intron DNA, as well as intron
      DNA alone, were found to inactivate the hprt gene and result in a selectable HPRT
      phenotype. Among the deletion mutants, however, only 21% of the spontaneous
      mutants versus 55% of both the X-radiation- and radon-induced mutants exhibited
      loss of the entire hprt gene. More X-radiation-induced deletions than radon
      induced deletions extended further than 800 bp in the telomeric direction from
      the hprt gene (six of 17 versus two of 17). The results show that at the human
      hprt locus of TK-6 cells the predominant kind of mutation indicative of exposure
      to both high LET alpha-radiation and low LET X-radiation is a large deletion,
      spanning the entire hemizygous hprt gene and extending into flanking sequences.

PMID- 7528878
TI  - Application of a multiple fixation regimen to study the adaptive response to
      ionizing radiation in lymphocytes of two human donors.
AB  - The majority of experiments studying the adaptive response using chromosomal
      aberrations have been performed with proliferating lymphocytes. It is known that
      lymphocytes have variable cell cycle transit times and it has been pointed out
      that in such cases aberration scores obtained from a single harvest are not very
      meaningful because cells harvested together in metaphase at any one time after
      irradiation were in different parts of the cell cycle at the time of irradiation.
      The scored sample will thus always contain a mixture of cells having different
      radiosensitivities and any variations of cell proliferation will influence the
      aberration score. In order to get a more representative aberration score a
      multiple fixation regimen was applied to lymphocytes of two human donors. Cells
      receiving the adapting + challenging and the challenging dose were fixed at three
      intervals after the challenge. In lymphocytes of donor 1 no adaptive response was
      seen at any fixation time in two experiments. In lymphocytes of donor 2, however,
      a reduction of aberration frequencies was seen, but at different fixation times
      in the two experiments. In a third experiment, no adaptive response was detected.
      It is concluded that the response observed at some fixation times in lymphocytes
      of donor 2 is rather a result of some phenomenon associated with variations of
      cell cycle kinetics than of induced radiation resistance.

PMID- 7528879
TI  - Retinoblastoma: a model for deriving the mutation rate without using any estimate
      of the size of the population at risk.
AB  - Paediatric cancer of the retinae arises from a transient population of stem cells
      whose growth and decay are responsible for the development of the fully
      differentiated photo-receptors and nerve cells. A model is described which fits
      the data on the incidence of bilateral retinoblastoma and gives the somatic
      mutation rate without using an estimate of the size of the population at risk. It
      also gives the shape of the retinoblast growth/decay curve. The model has been
      tested on two independent sets of data from the USA, and given that both sets are
      representative of the USA as a whole, there seems to have been little change in
      the somatic mutation rate over the last 30 or so years. For a total retinoblast
      formation of 4 x 10(6) cells, the average mutation rate is 2.94 x 10(-7) per cell
      per year.

PMID- 7528876
TI  - Agonist-induced photoincorporation of a p-benzoylphenylalanine derivative of
      substance P into membrane-spanning region 2 of the Torpedo nicotinic
      acetylcholine receptor delta subunit.
AB  - The neuropeptide substance P acts, at micromolar concentrations, as a
      noncompetitive antagonist of nicotinic acetylcholine receptors (AChRs) of both
      neuronal and muscle subtypes. The mechanism of this inhibition has been shown to
      be most consistent with stabilization of a nonconducting desensitized state of
      the AChR, via binding to a site distinct from both the agonist site and the high
      affinity noncompetitive antagonist site. We have used a radioiodinated
      photoreactive analogue of substance P, containing the amino acid p-benzoyl-L
      phenylalanine in place of the Phe8 residue of substance P, to identify the sites
      of interaction of substance P within the Torpedo california AChR. AChR-rich
      membrane suspensions were photolabeled in the absence or presence of the agonist
      carbamylcholine and/or nonradioactive substance P, and incorporation into AChR
      subunits was assessed by autoradiography after sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. In the absence of agonist 125I incorporation
      was detected in each subunit and was insensitive to substance P, whereas in the
      presence of carbamylcholine there was a 2-fold increase in photoincorporation
      into the AChR delta subunit that was inhibited by the addition of an excess of
      substance P. The sites of specific photoincorporation in the delta subunit were
      initially mapped by use of Staphylococcus aureus V8 protease to a 14-kDa fragment
      extending from delta Ile-192 to Glu-280. Further fragmentation of this 14-kDa
      fragment with trypsin and S. aureus V8 protease established that the sites of
      specific incorporation were restricted to the region delta Ser-253 to Glu-280,
      which contains the membrane-spanning region 2 that is known to form the lining of
      the ion channel. These results establish that in the presence of agonist at least
      a part of the undecapeptide substance P binds within the ion channel in the
      desensitized state of the AChR, and it is likely that the binding of substance P
      to this site is responsible for the action of substance P as a noncompetitive
      AChR antagonist.

PMID- 7528880
TI  - Enhancement of cytogenetic damage and of antineoplastic effect in lymphoid L1210
      leukemia cells treated with prostaglandin E2 and cyclophosphamide in vivo.
AB  - An enhanced frequency of sister-chromatid exchanges (SCEs) and increased cell
      division delays induced by cyclophosphamide (CP) were observed when lymphoid
      L1210 leukemia cells were post-treated in vivo with prostaglandin E2 (PGE2). CP
      gave a slight, non-significant increase in survival while PGE2 gave a slight, non
      significant decrease in survival. However, PGE2 in combination with CP was found
      to have a non-significant potentiating effect on survival in comparison with mice
      treated with CP alone. In mice treated with the combined CP (5 micrograms/g b.w.)
      plus PGE2 (2 micrograms/g b.w.) treatment, a significant (P < 0.01) enhancement
      of survival time in comparison with the untreated controls was observed.

PMID- 7528881
TI  - UV-induced mutagenesis in the endogenous hprt gene and in hprt cDNA genes
      integrated at different positions of the human genome.
AB  - The influence of the genomic position of a gene on UV-induced mutations was
      studied in the endogenous hprt gene in human lymphoblastoid TK6 cells and in cell
      lines derived from TK6 each containing a single copy of a hamster hprt cDNA gene
      integrated on a retroviral vector in different positions of the human genome.
      Previous studies showed that the genomic sequences surrounding the integration
      site influence spontaneous mutagenesis, resulting in a 10-fold difference in
      mutation rates among the hprt cDNA genes. Here we demonstrate that the genomic
      positions of three integrated hprt cDNA genes do not influence UV-induced
      mutagenesis. The mutability by UV irradiation in these cell lines is
      approximately the same (16.0 x 10(-6) per J/m2). The nature of the UV-induced
      mutations determined in two of the cell lines containing the integrated hprt cDNA
      gene (approximately 30 mutants each) was also found not to be different. The
      endogenous hprt gene in the parental TK6 cells exhibits a significantly lower
      mutability (2.1 x 10(-6) per J/m2) than the cDNA genes, but the spectrum is very
      similar. The spectrum in TK6 shows no influence of strand-specific repair and
      resembles most closely the spectrum obtained by McGregor et al. after irradiation
      of human cells synchronized in S-phase. This suggests that mutations arising in
      cells that are in S-phase at the time of irradiation constitute the majority of
      the mutants in an asynchronous TK6 cell population. We hypothesize that repair in
      the endogenous hprt gene in TK6 cells is very efficient, removing virtually all
      lesions before replication takes place except in cells that were in S-phase at
      the time of irradiation when there is not enough time for repair. Furthermore we
      suggest that the higher mutability of the integrated hprt cDNA genes compared
      with the endogenous gene is caused by a less efficient repair in the cDNA genes.

PMID- 7528882
TI  - Correlation of doxorubicin footprints with deletion endpoints in lacO of E. coli.
AB  - This study explored the possibility that the sequence location of doxorubicin
      induced deletion endpoints might relate to DNA structural alterations caused by
      doxorubicin binding to DNA. The 3'-OH endpoints of doxorubicin-induced deletions
      terminating in the 35-bp region of lacO appear to distribute differently from
      spontaneous deletion endpoints. Doxorubicin-induced deletions focus in the 26-bp
      palindrome which is separated by a 9-bp region with no reverse complementary,
      whereas spontaneous deletion 3'-OH endpoints are found distributed throughout the
      operator region. In order to explore the mechanism of deletion induction by
      doxorubicin, drug footprinting studies were carried out with DNA labeled at the
      5' end of each of the complementary DNA strands encompassed by lacO. Doxorubicin
      protected the 9-bp region between the palindromic sequences from DNase I cutting
      and caused enhanced DNase I cleavage at symmetrical sites in the palindrome,
      which were inherently resistant to the nuclease in the absence of the drug. These
      symmetrical sites also define regions in which the occurrence of deletion
      endpoints is enhanced 6-fold in the presence of doxorubicin. This enhanced
      cutting and mutation occur in regions of the palindrome that are flanked by
      expected doxorubicin binding sites, but are not themselves binding sites of the
      drug. Similarly, other sites where the frequency of deletion endpoints increased
      in response to doxorubicin occurred directly adjacent to regions where
      doxorubicin appeared to inhibit cutting by DNase I. These results suggest that
      the binding of doxorubicin in the palindrome directs both the frequency and the
      specificity of deletion formation in this gene region.

PMID- 7528883
TI  - Are base substitution and frameshift mutagenesis pathways interrelated? An
      analysis based upon studies of the frequencies and specificities of mutations
      induced by the (+)-anti diol epoxide of benzo[a]pyrene.
AB  - (+)-anti-B[a]PDE-induced mutagenesis is being investigated, including in a supF
      gene of the E. coli plasmid pUB3. Based upon various findings a working
      hypothesis was proposed that the major adduct of (+)-anti-B[a]PDE (formed at N2
      Gua) is able to induce different base substitution mutations (e.g., GC-->TA vs.
      GC-->AT vs. GC-->CG) depending upon its conformation in DNA, which can be
      influenced by various factors, such as DNA sequence context. Frameshift mutations
      are also significant and are analyzed herein. In virtually all cases one of three
      possibilities is observed: (1) some treatments change frameshift and base
      substitution mutation frequency (MF) in a quantitatively parallel fashion; (2)
      other treatments, which change frameshift MF, can change base substitution MF in
      a quantitatively reciprocal fashion; finally, (3) there are treatments that do
      not change frameshift MF, and also do not change base substitution MF. (Changes
      can be brought about by SOS induction, differing DNA sequence context, or heating
      adducted pUB3 prior to transformation. Why different kinds of changes result in
      (1) vs. (2) vs. (3) is discussed.) Thus, base substitution and frameshift
      mutagenesis pathways appear to be coupled in some way, which is most easily
      rationalized if both pathways are interrelated. The simplest mechanism to
      rationalize this coupling is that a single (+)-anti-B[a]PDE adduct in a single
      conformation can be bypassed via either a frameshift or a base substitution
      pathway. The surprising implication is that--although different conformations are
      likely to be required to induce different base substitution mutations (e.g., GC-
      >TA vs. GC-->AT; see above)--a single conformation can give rise to either a base
      substitution or a frameshift mutation. Frameshift and base substitution pathways
      must eventually diverge, and it is proposed that this is controlled by factors
      such as DNA sequence context.

PMID- 7528884
TI  - Physical mapping of the human hprt chromosomal region (Xq26).
AB  - The human hprt chromosomal region (Xq26) was physical-mapped using pulsed field
      gel electrophoresis (PFGE). This work involved: (i) the recovery of three new
      genomic DNA markers (DXS1327, DXS1328, and DXS1329), (ii) the ordering of new
      markers relative to 11 previously available hprt-linked markers by deletion
      mapping, and (iii) the completion of human T-lymphocyte PFGE Southern blots using
      the 14 Xq26 markers. A contiguous 1.5-Mb physical map of the region telomeric to
      hprt was determined. As this map identifies clusters of in vivo unmethylated rare
      cutter restriction sites, potential CpG islands are revealed.

PMID- 7528886
TI  - Establishment and validation of a dose-effect curve for gamma-rays by cytogenetic
      analysis.
AB  - A dose-effect curve obtained by analysis of dicentric chromosomes after
      irradiation of peripheral blood samples, from one donor, at 11 different doses of
      gamma-rays is presented. For the elaboration of this curve, more than 18,000
      first division metaphases have been analyzed. The results fit very well to the
      linear-quadratic model. To validate the curve, samples from six individuals
      (three controls and three occupationally exposed persons) were irradiated at 2
      Gy. The results obtained, when compared with the curve, showed that in all cases
      the 95% confidence interval included the 2 Gy dose, with estimated dose ranges
      from 1.82 to 2.19 Gy.

PMID- 7528885
TI  - Pulsed field analysis of hprt T-cell large deletions: telomeric region breakpoint
      spectrum.
AB  - In order to determine a large deletion breakpoint spectrum, 25 independent hprt T
      lymphocyte mutants with deletions extending from hprt into the telomeric or
      centromeric flanking chromosomal region were analyzed by pulsed field gel
      electrophoresis (PFGE). PFGE was used to determine deletion sizes which allowed
      localization of breakpoints external to hprt to specific chromosomal positions in
      mutants containing an intra-hprt breakpoint. A breakpoint spectrum based on 19
      large deletion mutants is reported for the Xq26 chromosomal region telomeric to
      hprt. A potential cluster of breakpoints (4/19) was observed approximately 60 kb
      from hprt. In addition, maximum recoverable deletion size was at least 3.5 Mb.
      Three of the 25 mutants analyzed appeared to be complex deletion events.

PMID- 7528887
TI  - Blocking of DNA synthesis in vitro by a guanosine 2',3'-cyclic phosphate: a
      possible mechanism of chromosome aberrations induced by U5 snRNA.
AB  - U5 snRNA can induce both transformation and chromosome aberrations of cells. The
      polypurine tract, GGAGAGGAA, of the RNA has been suggested to participate in both
      phenomena. In vitro transcription expected to give this polypurine
      oligoribonucleotide was associated with cleavage of transcripts, generating 5'
      terminal hydroxyl and 3'-terminal 2',3'-cyclic phosphate groups. The cleavage was
      further studied by making use of a Mg(2+)-catalyzed reaction and RNase T1 and
      RNase U2 digestion. The cleavage was found to generate highly reactive RNA
      molecules, participating in subsequent ligation of RNAs. Such a reactive
      molecule, guanosine-2',3'-cyclic phosphate, was capable of blocking DNA synthesis
      in vitro. The results may provide a possible mechanism of the chromosome
      aberrations induced by U5.

PMID- 7528889
TI  - Phases of the cell cycle sensitive to endoreduplication induction in CHO-K1
      cells.
AB  - We investigated the sensitive phase of the cell cycle for endoreduplication
      induction by colchicine, vanadate, 4-nitroquinoline 1-oxide (4NQO), and hydrazine
      in Chinese hamster CHO-K1 cells, compared to the metaphase endoreduplication
      inducer rotenone. Treatment of asynchronous cultures and 5-bromodeoxyuridine
      (BrdU) labeling analysis showed that the detected endoreduplications originated
      from cells which had been treated with these inducers in S, G2, or metaphase.
      Exposure to synchronized metaphase cells revealed that the inducers did not lead
      metaphase cells to endoreduplicate. These results were markedly different from
      that of rotenone and suggested that the target for the induction of
      endoreduplication by the tested compounds existed between at least S and G2
      phases.

PMID- 7528890
TI  - The biological activity of hydrogen peroxide. VI. Mechanism of the enhancing
      effects of L-histidine: the role of the formation of a histidine-peroxide adduct
      and membrane transport.
AB  - Further details of the mechanism of the enhancing effects of L-histidine (L-His)
      on the clastogenic activities of hydrogen peroxide (H2O2) were investigated. The
      L-His-H2O2 adduct was prepared and its physicochemical properties and biological
      activities were compared with those of a mixture of L-His plus H2O2 and of H2O2
      alone. When the stabilities of the three test samples against glucose were
      determined in terms of residual H2O2 content in solutions of various pH values
      over the course of 11 days, the adduct was found to be more stable than H2O2
      alone and very similar in terms of stability to the mixture. The almost
      equivalent stability of the adduct and the mixture suggested formation of the
      adduct in the mixture even though the interaction between L-His and H2O2 in
      solution seems, from 13C-NMR analysis, to be rather weak. In cell-free DNA after
      lysis of cell membranes, the induction of single-strand breaks (SSB) by the
      adduct and by the mixture was less effective than by H2O2 alone. These results
      contrast with previous results obtained in intact cells (Oya et al., 1992) and
      demonstrate the indispensability of the cell membrane for the enhancing effects
      of L-His. In the presence of inhibitors of the active transport of L-His, namely,
      10 different neutral amino acids, effective suppression of the clastogenic
      activity of the adduct and of the mixture was observed, whereas four acidic and
      basic amino acids had no effect. Thus, the participation of active transport in
      the enhancing effects of L-His was apparent. The formation of the adduct of L-His
      with H2O2 brings about the stabilization or reduces the reactivity of H2O2 and,
      as a result, the induction of SSB is prevented to some extent in cell-free DNA
      systems. By contrast, in a cellular system, the accumulation of the adduct in
      cells by active transport is potentiated by the enhancing effect of L-His,
      although the mediation of some factors that can generate hydroxyl radicals (*OH)
      from the adduct in cells must be postulated.

PMID- 7528892
TI  - Genetic changes and bioassays in bleomycin- and phleomycin-treated cells, and
      their relationship to chromosomal breaks.
AB  - The recombinogenicity of damaged chromosomes in diploid Saccharomyces cerevisiae
      cells treated with bleomycin and structurally related phleomycin was measured,
      along with aneuploidy and mutation events. Phleomycin was substantially (up to 26
      fold) more effective than bleomycin in producing genetic changes at all
      concentrations, even when colony-forming abilities of cells growing in the
      presence of bleomycin or phleomycin were similar. These results suggest that the
      DNA lesions produced by the two structurally related analogs could differ in
      their nature or frequency, or could be processed differently by the cells.
      Bioassays were developed and used to compare the cytotoxicities of freshly
      dissolved bleomycin and phleomycin with the cytotoxicities of lysates prepared
      from bleomycin- and phleomycin-treated cells. Unexpectedly, lysates prepared from
      bleomycin-treated cells were 1.5-3.5 times more cytotoxic than freshly dissolved
      bleomycin after 45-min treatments (3-33 x 10(-6) M). In contrast, lysates
      prepared from phleomycin-treated cells were 3-38 times less cytotoxic than
      freshly dissolved phleomycin (0.5-6.4 x 10(-6) M). Cytotoxicities of all lysates
      were higher after 36-h treatments than after 45-min treatments. At 3.3 x 10(-6)
      M, this increase was eightfold for bleomycin and 15-fold for phleomycin.
      Nevertheless, lysates from phleomycin-treated cells were considerably more
      cytotoxic than lysates from bleomycin-treated cells or freshly prepared
      bleomycin, consistent with the higher effectiveness of phleomycin than bleomycin
      in producing chromosomal breaks, genetic changes, and cell killing.

PMID- 7528891
TI  - DNA double-strand break repair in two radiation-sensitive mouse mammary carcinoma
      cell lines.
AB  - The capacity of two radiation-sensitive clones (SX9 and SX10) of the mouse
      mammary carcinoma cell line SR1 to rejoin radiation-induced DNA double-strand
      breaks (DSBs) was determined by pulsed-field agarose gel electrophoresis. DSBs
      were produced with equivalent efficiency in all three cell lines. Both the SX9
      and SX10 cell lines demonstrated a significantly diminished capacity to rejoin
      radiation-induced DSBs. The fraction of the original DNA DSB damage remaining in
      the DNA of 20 Gy-exposed SR1, SX9 and SX10 cells after 6 h of 37 degrees C
      incubation was estimated to be 14, 82 and 54%, respectively. In addition the SX10
      cell line exhibited enhanced cytotoxicity when exposed to the DNA topoisomerase
      II poison mitoxantrone. The results indicate that both the SX9 and SX10 cell
      lines are DNA DSB repair mutants.

PMID- 7528888
TI  - Molecular structural analysis of 417 HPRT mutations induced by restriction
      endonucleases in Chinese hamster ovary (CHO) cells.
AB  - CHO cells were exposed to 11 different restriction endonucleases by
      electroporation and their mutagenicity was measured. Nine of them have one or
      more recognition sites within exons of the HPRT gene, whereas the remaining two
      cut in introns only. The mutagenic efficiency of the various enzymes varied
      markedly; mutagenicity of Sau3AI was considerably higher than that of the other
      enzymes. Neither cytotoxicity nor mutagenicity could be related to the number or
      location of recognition sites within the cDNA. A total of 417 independent
      restriction enzyme induced mutant clones were isolated from 20 separate
      experiments for molecular analysis; all nine exons of the HPRT gene were analyzed
      by a modified multiplex deletion screening method with polymerase chain reaction
      (PCR) amplification. Among spontaneously arising mutants, 70.8% showed no change
      in PCR pattern, indicating a small scale change (point mutation), whereas partial
      deletions were observed in 24.7%, and total deletions in 4.5% of mutant clones.
      In contrast, approximately 70% of restriction enzyme induced mutants showed
      partial or total deletions. There was no obvious relationship between type of
      break (blunt versus staggered ends), and the DNA structure of the mutations
      induced. For partial deletions, the distribution of breakpoints within introns
      appeared to occur at random, and did not correlate with the mutagenicity of a
      given enzyme. Thus, though DNA double-strand breaks appear to be important
      mutagenic lesions that can induce a high frequency of deletion mutants, no
      specific relationship of mutagenic potential to the type of breaks, their sites
      within the HPRT gene or the molecular structure of the mutations induced could be
      identified.

PMID- 7528893
TI  - Effect of activated oxygen species in human lymphocytes.
AB  - The cytogenetic effectiveness of activated oxygen species (AOS) generated by the
      superoxide forming xanthine-xanthine oxidase (X/XO) system was studied in human
      lymphocyte cultures. The observed chromosome damage was exclusively of the
      chromatid type. In the experiments a clear dependence of aberration induction on
      XO concentration and exposure time could be demonstrated. While using anti-AOS
      agents, the H2O2 antagonist catalase and the hydroxyl radical scavenger formate
      reduced X/XO induced chromosome damage whereas superoxide dismutase (SOD) did
      not. In the presence of SOD, aberration frequency was even enhanced. The results
      indicate that the chromosome damage is caused indirectly via H2O2 formation from
      spontaneous dismutation of superoxide, whereas H2O2 might be reduced
      intracellularly giving rise to the highly reactive hydroxyl radical. This effect
      might be enhanced by SOD, possibly by raising the intracellular amount of easily
      membrane passing H2O2. Thus, referring to chromosome aberrations, SOD, which is
      generally reported to protect from AOS, is capable of increasing oxygen mediated
      biological damage. This observation might be explained by the involvement of DNA
      associated transition metal, like iron or copper ions, in reducing H2O2. DNA
      bound copper ions, thought to be necessary for maintenance of DNA quaternary
      structure, might represent a generator complex for the hydroxyl radical by
      reduction of X/XO derived hydrogen peroxide. This might cause 'site specific
      damage' to the DNA which is subsequently converted into chromatid-type aberration
      by S-dependent misreplication and/or misrepair. This is different to the
      formation of radiation induced chromosome aberrations which arise by an S-phase
      independent mechanism.

PMID- 7528894
TI  - Analysis of recA mutants with altered SOS functions.
AB  - The Escherichia coli RecA protein has at least three roles in SOS mutagenesis:
      (1) derepression of the SOS regulon by mediating LexA cleavage; (2) activation of
      the UmuD mutagenesis protein by mediating its cleavage; and (3) targeting the Umu
      like mutagenesis proteins to DNA. Using a combined approach of molecular and
      physiological assays, it is now possible to determine which of the three defined
      steps has been altered in any recA mutant. In this study, we have focused on the
      ability of six particular recA mutants (recA85, recA430, recA432, recA433,
      recA435 and recA730) to perform these functions. Phenotypically, recA85 and
      recA730 were similar in that in lexA+ and lexA(Def) backgrounds, they exhibited
      constitutive coprotease activity towards the UmuD mutagenesis protein. Somewhat
      surprisingly, in a lexA(Ind-) background, UmuD cleavage was damage inducible,
      suggesting that the repressed level of the RecA* protein cannot spontaneously
      achieve a fully activated state. Although isolated in separate laboratories, the
      nucleotide sequence of the recA85 and recA730 mutants revealed that they were
      identical, with both alleles possessing a Glu38-->Lys change in the mutant
      protein. The recA430, recA433 and recA435 mutants were found to be defective for
      both lambda mutagenesis and UmuD cleavage. lambda mutagenesis was fully restored,
      however, to the recA433 and recA435 strains by a low copy plasmid expressing the
      mutagenically active UmuD' protein. In contrast, lambda mutagenesis was only
      partially restored to a recA430 strain by a high copy UmuD' plasmid, suggesting
      that RecA430 may also be additionally defective in targeting the Umu proteins to
      DNA. Sequence analysis of the recA433 and recA435 alleles revealed identical
      substitutions resulting in Arg243-->His. The recA432 mutation had a complex
      phenotype in that its coprotease activity towards UmuD depended upon the lexA
      background: inducible in lexA+ strains, inefficient in lexA(Ind-) cells and
      constitutive in a lexA(Def) background. The recA432 mutant was found to carry a
      Pro119-->Ser substitution, a residue believed to be at the RecA subunit
      interface; thus this complex phenotype may result from alterations in the
      assembly of RecA multimers.

PMID- 7528895
TI  - Pulsed-field gel electrophoresis analysis of the repair of psoralen plus UVA
      induced DNA photoadducts in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, double-strand breaks (DSB) have been
      observed during the DNA repair of psoralen plus UVA induced lesions. In the
      present paper, we analyzed this repair step in some detail using pulsed-field gel
      electrophoresis (CHEF) to get a better understanding of this phenomenon with
      regard to the type of lesions induced and the repair pathways involved. The
      results confirm that, during post-treatment incubation of Saccharomyces
      cerevisiae cells, DSB are formed. Their appearance is dose-dependent and the rate
      of induction is comparable in large (chromosome IV) and small (chromosome III)
      chromosomes. The formation of DSB is evidenced by the breakage of linear
      chromosomes III and IV, but also, after high doses, by the linearization of a
      circular form of chromosome III. The induction of DSB appears to be highly
      dependent on the induction of interstrand cross-links since they are clearly
      present after treatments with 8-MOP plus 365 nm radiation (inducing monoadducts
      and cross-linking in DNA), but practically absent after treatment with 8-MOP plus
      405 nm radiation (inducing predominantly monoadducts) at comparable levels of
      photoadducts. The occurrence of DSB is dependent on the RAD2 and RAD52, but not
      on the RAD6 gene. It is likely that the specific processing of DNA lesions
      involving DSB is related to the genotoxic consequences observed.

PMID- 7528896
TI  - Inactivation of O6-methylguanine-DNA methyltransferase in vivo by SN2 alkylating
      agents.
AB  - The cellular level of O6-methylguanine-DNA methyltransferase (MGMT) is important
      in mutagenic, carcinogenic and therapeutic effects of alkylating agents. I have
      investigated how SN2 alkylating agents affect the activity of MGMT in vivo. As a
      model, adapted cultures of E. coli K12 strain AB2497 containing 2400 +/- 430
      molecules of MGMT per cell were used. MGMT activity was assayed in the cell
      extracts of adapted cultures challenged with various doses of MMS, DMS and for
      comparison the SN1 alkylating agents, MNNG and MNU. In control non-adapted
      cultures, with low constitutive levels of MGMT, the mutagenic potential of
      various doses of different alkylating agents was estimated to correlate with the
      O6-methylguanine content produced in DNA by various treatments. Inactivation of
      MGMT by MNNG or MNU occurs only in doses able to produce a highly mutagenic level
      of O6-methylguanine in DNA, which is consistent with the consumption of MGMT
      activity in the DNA repair process. In contrast, non-mutagenic doses of MMS or
      DMS are sufficient to inactivate MGMT in adapted E. coli cells. It may be
      concluded that SN2 alkylating agents can block the main pathway of O6
      methylguanine-DNA repair in vivo.

PMID- 7528897
TI  - The kinetics of repair of oxidative DNA damage (strand breaks and oxidised
      pyrimidines) in human cells.
AB  - Single cell gel electrophoresis is a sensitive method for detecting DNA strand
      breaks. Cells embedded in agarose are converted to nucleoids by treating with
      detergent and high salt. DNA breaks render the nucleoid DNA susceptible to
      extension by electrophoresis, forming 'comets'. We find that when DNA breakage
      resulting from H2O2 treatment is examined, freshly isolated normal human
      lymphocytes are relatively resistant compared with transformed human cells. When
      incubated after treatment with H2O2, HeLa cells repair most strand breaks within
      1 h, and a substantial fraction of the oxidised pyrimidines (detected by
      converting them to DNA breaks with endonuclease III) within 4 h. However,
      lymphocytes are less proficient at repair; during incubation for 4 h after
      treatment with H2O2, no detectable removal of endonuclease III-sensitive sites is
      seen. While the addition of deoxyribonucleosides promotes completion of repair of
      UV damage by lymphocytes, it has no significant effect on repair of oxidative
      damage.

PMID- 7528898
TI  - Evidence for a weak adaptive response to alkylation damage in Vibrio cholerae.
AB  - Wild-type Vibrio cholerae cells, when adapted by a stepwise treatment with sub
      lethal concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), acquired
      resistance to killing and mutagenesis by subsequent challenges with higher
      concentrations of MNNG. This was also seen in the rec isogenic strain indicating
      that the observed phenomenon was not due to the induction of SOS functions.
      Further, the adapted cells of both the wild-type and rec strains could reactivate
      lethally alkylated phages with equal efficiency. Increased resistance of adapted
      cells correlated with the induction of a 17-kDa DNA methyltransferase, capable of
      repairing O6-methylguanine lesions in DNA. This induced methyltransferase was
      found to be antigenically unrelated to the Escherichia coli methyltransferase
      (Ada protein) as determined by Western blotting with polyclonal antiserum raised
      against the E. coli protein. Even though no counterpart of the constitutively
      expressed methyltransferase (Ogt) of E. coli could be detected in V. cholerae,
      several lines of evidence pointed towards the presence of an E. coli alk A-like
      gene in the organism.

PMID- 7528900
TI  - Host-cell reactivation of reporter genes introduced into cells by adenovirus as a
      convenient way to measure cellular DNA repair.
AB  - In order to conveniently measure cellular DNA repair in immortalized and primary
      human cells we have combined the features of high cellular infectivity of
      adenovirus (Ad) with that of host-cell reactivation (HCR) of ultraviolet light
      (UV)-damaged reporter genes. We show that Ads having either the cat
      (chloramphenicol acetyltransferase) or seap (secreted alkaline phosphatase)
      reporter gene under control of a strong constitutive promoter can be used to
      measure relative levels of DNA repair by HCR. Most importantly, the SEAP assay
      allows for a convenient, inexpensive, and sensitive colorimetric microtiter
      assay. Only a few steps are involved and it is possible to process many samples
      simultaneously in a relatively short time, which is not as easily done with other
      reporter gene assays. Furthermore, we show that co-infection of UV-damaged SEAP
      Ad with an Ad carrying a prokaryotic repair gene significantly increased the HCR
      levels in xeroderma pigmentosum cells. The Ad gene delivery system, and the SEAP
      assay in particular, should simplify existing HCR assays considerably. By using
      non-lytic Ad as a vehicle it should be possible to quantitatively introduce
      normal or dominant negative mutant DNA repair genes into bulk cell populations
      for DNA repair studies.

PMID- 7528899
TI  - Overexpression of N-methylpurine-DNA glycosylase in Chinese hamster ovary cells
      renders them more sensitive to the production of chromosomal aberrations by
      methylating agents--a case of imbalanced DNA repair.
AB  - The main N-alkylation products induced in DNA by methylating mutagens (7
      methylguanine, 3-methyladenine, 3-methylguanine) are removed by excision repair
      involving, in the first step of the repair pathway, N-methylpurine-DNA
      glycosylase (MPG). To elucidate the significance of excision repair of N
      alkylpurines in the defense of cells against alkylating agents we have modulated
      the efficiency of removal of N-methylpurines in Chinese hamster cells by
      transfecting them with the human MPG cDNA cloned into a mammalian expression
      vector. Although the stably transfected cells had a significantly higher capacity
      for removal of N-methylpurines from DNA, they did not gain protection against the
      cytotoxic and mutagenic effect of alkylating agents. The cells even responded
      more sensitively with respect to SCE formation. Here we show that the frequency
      of chromosomal aberrations induced by methyl methanesulfonate and N-methyl-N'
      nitro-N-nitrosoguanidine is significantly enhanced in the transfectants.
      Furthermore the transfectants showed a stronger inhibition of DNA replication and
      a higher yield of DNA breaks, as measured several hours after methylating agent
      exposure. The data suggest that overexpression of MPG causes an imbalance in the
      multi-step process of excision of N-methylpurines from DNA giving rise to a high
      yield of apurinic sites and/or gapped DNA that are intermediates in the formation
      of chromosomal aberrations, SCEs and the inhibition of replication in cells
      exposed to alkylating agents.

PMID- 7528901
TI  - CD44 plays a role in adhesive interactions between glioma cells and extracellular
      matrix components.
AB  - Glioma invasion is a complex process involving interactions of tumour cells with
      host cells and extracellular matrix (ECM). The initial event in the process is
      recognition and attachment of glioma cells to specific ECM molecules prior to
      migration into proteolytically modified matrix. In comparison with other tissues,
      brain ECM is a relatively amorphous matrix which contains glycosaminoglycans
      including hyaluronan (HA). Recently CD44 which is a transmembrane adhesion
      molecule found on a wide variety of cells, has been suggested as the principal
      cell surface receptor for HA. In the present in vitro investigation we have
      analysed the role of CD44 in adhesive interactions between human gliomas and ECM.
      Our experimental procedures included immunocytochemistry, immunoblotting, in
      vitro adhesion assay and flow cytometry. CD44 was expressed on the surface of all
      gliomas analysed (9) and the level of expression showed no correlation with
      tumour grade. Eighty, 95 and 120 kDa isoforms were demonstrated by
      immunoblotting. In an adhesion blocking assay it was found that ligation of CD44
      with specific antibody resulted in reduced adhesion to hyaluronan, chondroitin
      sulphate, fibronectin, laminin, collagen IV and Matrigel. We conclude that CD44
      is involved in adhesion of glioma cells to a wide range of ECM components.

PMID- 7528902
TI  - Recurrence of primary intracranial germinomas after complete response with
      radiotherapy: recurrence patterns and therapy.
AB  - Nine germinoma patients are described who developed a recurrence after a complete
      response to radiation without adjuvant chemotherapy. Extraembryonic tumors
      producing alpha-fetoprotein and human chorionic gonadotropin were excluded from
      this study. Four patterns of recurrence are described with respect to mechanism
      and appropriate treatment. Type I germinoma recurrence, characterized by
      intracranial recurrence caused by an inadequate initial irradiation field was
      treated by total craniospinal irradiation. Type II recurrence, characterized by a
      benign teratoma caused by late growth of the teratoma component was treated by
      surgery alone. All patients with these patterns of recurrence are still alive.
      Type III local recurrence is characterized by human chorionic gonadotropin- or
      alpha-fetoprotein-producing tumors of extraembryonic origin. This pattern of
      recurrence should be treated by chemotherapy or radiosurgery, because all these
      patients died. Type IV germinoma recurrence consists of extraneural metastasis
      without evidence of intracranial recurrence. Two of these patients were treated
      with chemotherapy. In summary, four patients died after recurrence, whereas the
      remaining five patients survived. The classification of germinoma recurrence
      patterns should facilitate the selection of the most appropriate treatment.
      However, it has been difficult to identify the precise histopathology by biopsy
      or partial resection alone. Furthermore, chemotherapy is indicated in treating
      germinomas that have a ventriculoperitoneal shunt because of the risk of
      extraneural metastases.

PMID- 7528903
TI  - Topography of commissural fibers in the corpus callosum of the cat: a study using
      WGA-HRP method.
AB  - The topography of the commissural fibers in the corpus callosum (CC) of the cat
      was systematically investigated using the WGA-HRP method. WGA-HRP was injected
      into various parts of the cerebral cortex and locations of WGA-HRP-stained
      commissural fibers in the CC were examined. Commissural fibers were arranged in a
      topological fashion in the CC. Cortical areas rostral to the cruciate sulcus
      (CrS), corresponding to motor or premotor cortices, projected fibers into the
      genu of the CC, while fibers from the cortex caudal to the CrS passed through the
      CC slightly caudal to the genu. When WGA-HRP was injected into the lateral gyrus
      (LG), it was observed that fibers from the anterior LG passed through the
      anterior one-third of the CC, whereas those from the posterior LG passed through
      or near the splenium, and fibers from the middle LG passed between those from the
      anterior and posterior LG. Similarly, the suprasylvian gyrus (SSG) projected
      commissural fibers in the CC in a rostrocaudal topological manner. Fibers from
      the anterior SSG passed through the anterior one-third of the CC, and those from
      the middle SSG through the middle one-third of the CC and upper part of the
      splenium. Injection into the most posterior part of the middle SSG revealed
      fibers passing through the caudal end of the splenium. Callosal fibers from the
      anterior SSG were focused on in this study, because this area (area 2v) is
      considered one of the vestibular projection cortices and is an area of special
      interest to the authors. Callosal fibers from the anterior SSG were observed to
      pass through the anterior one-third of the body of the CC. When WGA-HRP was
      injected into auditory areas, fibers from the anterior and middle ectosylvian
      gyri (ESG) were observed to pass through the posterior one-third of the body of
      the CC or through the splenium, while fibers from the posterior ESG passed
      through the splenium. WGA-HRP was also injected into the cingulate gyrus (CiG).
      Fibers from the anterior CiG (area 24) passed through the anterior portion of the
      CC while those from the posterior CiG (area 23) passed through the posterior
      portion of the CC.

PMID- 7528905
TI  - [The role of local excision in the surgical treatment of rectal cancer].
AB  - Between 1984 and 1992 authors performed 307 surgical interventions for patients
      with rectal cancer, of these 199 operations were curative (65%). Local excision
      of the tumour was carried out in 9 cases: 2 with palliative intent, 7 were
      considered a curative treatment, that constituted 3.5% of all curative
      procedures. Five tumours were removed by transanal local excision, 2 located in
      the upper part of the rectum required laparotomy and rectotomy. No operative
      mortality. One wound sepsis was registered after laparotomy. There was one local
      recurrence after removing the primary tumour. At the same time 83 patients
      suffering abdominoperineal resection or anterior resection had tumour limited to
      the rectal wall without lymph node metastasis. The mortality was 1.4%, the
      morbidity 28% and local recurrence rate was 19% in this group. The difference
      between the the results of the two groups did not achieve statistical
      significance included the survival too. Of the 83 tumours removed by more radical
      operations 38 located between 1-8 cm from the anal verge. Excluding tumours
      poorly differentiated and those with diameter larger than 3 cm, 17 rectal cancer
      would have been suitable for transanal local excision, that constitutes 8.5% of
      the curative operations. CONCLUSION: with more accurate preoperative staging the
      transanal local excision for carcinoma of the rectum can be performed more
      frequently than earlier. The risk of the operation is lower than those of the
      abdominoperineal or anterior resection and the late results are comparable if
      strict selection criteria are implemented.

PMID- 7528904
TI  - Immunohistochemical examination of the relationship between two types of mucous
      neck cell and the intermediate cells in the rat fundic gland.
AB  - It is generally accepted that the mucous neck cells are the precursors of chief
      cells, and that they are converted to chief cells via intermediate cells. We
      reported previously that two types of mucous neck cell are present in the region
      close to the cardia of the rat fundic gland. Using immunoelectron microscopy and
      lectin histochemistry, we examined whether the two histochemically distinct types
      of mucous neck cell are converted to chief cells via intermediate cells by the
      same process. Intermediate cells were positive for immunostaining with an
      antibody raised against neutral mucin but negative for staining with Limax flavus
      agglutinin (LFA). It is proposed that the mucous neck cells that contain neutral
      mucin are converted to chief cells via intermediate cells. The cells containing
      acidic mucin are first converted to mucous neck cells that contain neutral mucin
      and then to chief cells via intermediate cells.

PMID- 7528906
TI  - [Malignant melanomas of the head and neck].
AB  - During 1980-1992 twelve patients with malignant melanoma of the head and neck
      were treated in the Department of Otolaryngology of Medical Academy in Warsaw.
      The largest group (eight patients) consisted of the cases with melanoma localized
      on the nasal mucosa. In next four patients the tumor localized on the skin of the
      head. The clinical course of the melanoma was discussed and its methods of cure
      in dependence on the degree of progression.

PMID- 7528907
TI  - Cellular and humoral responses to antigenic subunits of Echinococcus granulosus
      cyst fluid in hydatid patients.
AB  - The hydatid fluid antigenic subunits which stimulate the proliferative response
      of T cells in PBMC isolated by hydatid patients were identified. In the same
      subjects, the serum IgG antibody profiles were determined by immunoblotting to
      compare T cell activation and IgG production. The study was carried out on 18
      patients with clinically and serologically diagnosed hydatidosis and on ten
      healthy blood donors. To assess the proliferative response to the different
      antigenic subunits, sheep hydatid fluid was separated by the SDS-PAGE and the
      fractions were blotted onto nitrocellulose and solubilized. The comparison
      between immunoblotting and PBMC proliferation assay shows that the 55 and 65 kDa
      subunits of antigen 5 and the 12 kDa subunit of antigen B are the most reactive
      subunits in the two techniques. The 16 and 20 kDa subunits of antigen B are more
      reactive in PBMC proliferation assay than in immunoblotting, thus assigning a
      specific role to antigen B in cellular response.

PMID- 7528908
TI  - Precore mutant hepatitis B virus and outcome of chronic infection and hepatitis
      in hepatitis B e antigen-positive children.
AB  - Mutant hepatitis B virus (HBV), responsible for the lack of hepatitis B virus "e"
      antigen (HBeAg) secretion because of a translational stop codon at nucleotide
      1896 of the HBV-DNA precore region (HBeAg minus HBV), has been detected worldwide
      in acute and chronic HBV infections and diseases. HBeAg minus HBV appears to
      condition the outcome of infection and to be involved in the pathogenesis of
      hepatitis B. We investigated the mutant prevalence and its clinical implications
      in 30 hepatitis B surface antigen/HBeAg-positive children (17 treated with
      interferon) with chronic hepatitis B. Wild-type and HBeAg minus HBV were
      characterized by quantitative oligohybridization assays in sera from 29 children
      followed up for a mean of 33 mo (12 mo to 9 y). At admission, 18 children (62%)
      circulated wild-type HBV alone; mutant HBV became detectable in two of them
      during the follow-up before HBeAg/anti-HBe seroconversion. Wild-type and HBeAg
      minus HBV were detected in 10 children (34.5%); mutant HBV levels were lower than
      20% of total viremia in four of them and higher in six. Serum HBV-DNA from one
      child did not hybridize with our probes. HBeAg minus HBV was associated with
      older age (p < 0.009) and higher histologic activity (p < 0.069). HBeAg/anti-HBe
      seroconversion occurred independently from HBeAg minus HBV detection; it was
      observed in six (37.5%) of 16 children with wild-type HBV alone and in four
      (33.3%) of 12 children with mixed viremia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528909
TI  - Neuroretinitis in cat-scratch disease associated with the macular star.

PMID- 7528910
TI  - Motor apraxia in dementia.
AB  - Motor apraxia was assessed in 25 patients with presumed dementia of the Alzheimer
      type and 23 patients with presumed multi-infarct dementia. Apraxia was common in
      both groups and was usually only mild. It correlated most strongly with language
      related impairments in the Alzheimer group, as has been found in other patient
      groups, whereas in the group with multi-infarct dementia the pattern of
      correlations was less clear. It was not strongly related to performance on tests
      involving constructional praxis or to age in either group. Implications of the
      findings for clinical assessment are noted.

PMID- 7528911
TI  - Analysis of students' perceptual styles and their use of multimedia.
AB  - The relationships between students' perceptual styles (field independence
      dependence-neutral) and the students' preferences for visual images as well as
      written text and narrative sound within a multimedia lesson have been studied. Of
      particular importance was the students' study time (minutes) among three media.
      70 students of historic costume completed the Group Embedded Figures Test and a
      multimedia lesson distinguishing costumes of 1875, 1880, and 1885. Significantly
      more time was spent studying both visual images and written text than in
      listening to narrative sound; however, visual images were selected significantly
      more often than text or sound, in that order. Subjects chose and studied detailed
      fashion illustrations significantly more than the simplified line drawings and
      significantly increased their knowledge about costumes of 1875 to 1885. No
      association of students' perceptual style with any assessment procedure was
      noted.

PMID- 7528912
TI  - [The role of interferons in treating hematopoietic system neoplasms].

PMID- 7528914
TI  - [Bilateral multiple pulmonary coin lesions--adenoid cystic carcinoma of the lung
      with 14-year follow-up].
AB  - The authors report on an adenoid cystic carcinoma (ACC) of the lung that had been
      discovered by chance 14 years before the death of the patient and that had at
      first been interpreted morphologically as a metastatic lung or as a
      bronchioalveolar carcinoma. The patient remained without any complaints for 13
      years. Diagnosis of ACC became possible only by means of a renewed peripheral
      lung biopsy. An extrapulmonary primary tumour was excluded by postmortem
      examination. The disease pattern and the special course of the ACC are described.

PMID- 7528913
TI  - Transrectal fine needle aspiration biopsy of the prostate combining
      cytomorphologic, DNA ploidy status and cell cycle distribution studies.
AB  - Fine needle aspiration (FNA) cytology of the prostate is becoming a common
      diagnostic procedure, and DNA flow cytometry (FCM) data have been shown to
      correlate with the pattern of evolution of prostatic carcinoma, thus emphasizing
      the importance of assessing both parameters together. The aim of the present
      paper is to analyze the presence of DNA aneuploidy, cell cycle distribution and
      their relationship with the cytologic grade in transrectal fine needle aspiration
      prostate biopsies from 78 consecutive patients. Herein we studied the DNA ploidy
      status, the cell cycle distribution and their relationship with cytologic grade
      in transrectal FNA biopsies of the prostate from 78 consecutive patients -47
      benign hyperplasias and 31 carcinomas- as analyzed by a reproducible FCM method
      for single cell suspension preparations, data acquisition and analysis. The
      presence of DNA aneuploidy was detected in 39% of the carcinomas and it was found
      to be a specific marker for prostatic carcinoma since all benign hyperplasia
      cases were diploid. Moreover, the incidence of DNA aneuploidy increased
      progressively from well-differentiated to moderately-differentiated and poorly
      differentiated carcinomas (p = 0.005). Regarding cell cycle distribution,
      carcinomas displayed a higher proportion of both S-phase (p = 0.0003) and G2/M
      phase (p = 0.0006) cells with respect to benign hyperplasias. Aneuploid cases
      also showed a greater proliferation rate as compared to the diploid carcinomas,
      regardless of their cytopathologic grade (p = 0.00001). Despite the fore
      mentioned results, these correlations were far from being absolute, suggesting
      that combined assessment of these parameters should give additional information
      for the clinical management of prostatic disease.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7528916
TI  - Distribution of lipophosphoglycan-associated epitopes in different Leishmania
      species and in African trypanosomes.
AB  - Monoclonal antibody (mAb) CA7AE binds specifically to the phosphorylated Gal-beta
      1,4-Man disaccharide repeat epitope of Leishmania donovani lipophosphoglycan
      (LPG). This mAb detected the repeat epitope in most but not all of a wide variety
      of Leishmania species and strains examined. MAb CA7AE also bound to both
      glycoprotein and carbohydrate antigens in medium from L. donovani promastigote
      cultures. Specifically, mAb CA7AE bound the delipidated form of LPG, the
      phosphoglycan, and a glycoprotein both of which are released into the medium by
      the parasite indicating that both share a specific phosphorylated carbohydrate
      epitope. The epitope was detected in sera from L. donovani-infected (kala-azar
      positive) patients when mAb CA7AE was used in an antigen-capture enzyme-linked
      immunosorbent assay (ELISA). MAb L157 is specific for a protein that is found
      associated with L. donovani LPG, the lipophosphoglycan-associated protein
      (LPGAP). This mAb bound to molecules in all 19 strains (representing 9 species)
      of Leishmania promastigotes and to molecules in 2 species of Trypanosoma
      procyclic culture forms. This wide distribution of the LPGAP epitope implies that
      it may have a conserved function, for example, in the biochemistry or arrangement
      of parasite surface molecules. In addition, since the LPGAP is involved in the
      stimulation of T lymphocyte proliferation, its wide distribution amongst
      different Leishmania species suggests that it may be an ideal molecule for
      testing as a vaccine for leishmaniasis.

PMID- 7528917
TI  - Role of nitric oxide in the pancreatic blood flow response to caerulein.
AB  - To clarify the role of nitric oxide (NO) in the pancreas, blood flow in the rat
      pancreas (pancreatic blood flow: PBF) was investigated by the hydrogen clearance
      technique using a specific NO synthase inhibitor, N omega-nitro-L-arginine (L
      NNA). Continuous infusion of caerulein at doses of 5 and 20 micrograms/kg/h
      caused a significant increase in PBF in the early phase of caerulein infusion.
      The caerulein-induced increase in PBF was not affected significantly by atropine
      sulfate (100 micrograms/kg), nor by phenoxybenzamine (5 mg/kg) plus propranolol
      (50 micrograms/kg). Administration of L-NNA (0.5, 5, or 30 mg/kg) did not affect
      the basal PBF, but at 5 mg/kg it inhibited completely the caerulein-induced
      increase in PBF. The inhibitory action of L-NNA was reversed by a large dose of L
      arginine (100 mg/kg bolus, i.v., followed by a continuous infusion at 400
      mg/kg/h), but not by its enantiomer D-arginine. These results strongly suggest
      that NO has a mediator role in the early phase vascular response of the pancreas
      to superphysiologic doses of caerulein.

PMID- 7528915
TI  - Mechanisms for the elimination of potentially lytic complement-fixing variable
      surface glycoprotein antibody-complexes in Trypanosoma brucei.
AB  - Live antibody-coated Trypanosoma brucei parasites remove variable surface
      glycoprotein (VSG)-antibody complexes from their surface upon warming to 37
      degrees C and evade antibody-activated complement lysis by both protein synthesis
      dependent and protein synthesis-independent mechanisms. The protein synthesis
      dependent process follows antibody-mediated trypanosome agglutination, whereas
      the protein synthesis-independent mechanism can occur in the absence of
      trypanosome agglutination. The latter process leads to a more rapid elimination
      of complement-fixing VSG-antibody complexes.

PMID- 7528918
TI  - Acetylcholine, ATP, bombesin, and cholecystokinin stimulate 125I efflux from a
      human pancreatic adenocarcinoma cell line (BxPC-3).
AB  - We have studied the effects of acetylcholine (ACh), and other agents that
      modulate pancreatic bicarbonate secretion, on the anion permeability of a human
      ductal adenocarcinoma cell line (BxPC-3). Anion permeability was monitored using
      an 125I efflux assay. ACh (10 microM) markedly stimulated 125I efflux from BxPC-3
      cells and this response was abolished by atropine (10 microM), indicating that it
      is mediated by muscarinic receptors. Using transport inhibitors and ionophores,
      we obtained data indicating that some of the ACh-induced 125I efflux results from
      the opening of K+ channels, which would hyperpolarise the cell and increase the
      electrical driving force for 125I exit. The remaining ACh-induced 125I efflux is
      not mediated by anion exchangers or by Na+/K+/2Cl- cotransporters, and is
      probably explained by activation of an anion channel in the BxPC-3 cell membrane.
      Ionomycin (0.5 microM) caused a small rise in 125I efflux, indicating that this
      process can be triggered by an increase in intracellular calcium concentration.
      ATP (100 microM), ADP (100 microM), bombesin (10 nM), and cholecystokinin (CCK)
      (10 nM) also stimulated 125I efflux, indicating that receptors for these agents
      are expressed on BxPC-3 cells. We speculate that bicarbonate secretion from the
      human pancreas could be modulated by ACh, ATP, bombesin, and CCK via a direct
      effect on the duct cell.

PMID- 7528919
TI  - Evidence for a large dispensable segment in the subtilisin-like catalytic domain
      of the Lactococcus lactis cell-envelope proteinase.
AB  - The Lactococcus lactis SK11 cell-envelope proteinase contains various inserts,
      located in external loops of the catalytic domain compared with related
      subtilisins. In this study, protein engineering was employed to determine the
      function of the largest loop insertion (residues 238-388) relative to the
      subtilisin structure. By site-directed mutagenesis we have deleted the fragment
      of the proteinase gene encoding these 151 residues and analyzed the mutant delta
      238-388 proteinase for activity, (auto)processing and cleavage specificity. This
      extra segment is found to be inessential for activity, and its removal does not
      inhibit folding as the mutant proteinase is still active. In addition, the N- and
      C-terminal autoprocessing of the delta 238-388 proteinase appears to be
      unchanged. However, removal of residues 238-388 altered substantially the
      caseinolytic specificity of the enzyme, indicating that this extra segment
      influences substrate specificity. Residues 238-388 were shown to contain a
      specific epitope for a monoclonal antibody.

PMID- 7528920
TI  - Extracellular matrix-dependent tissue-specific gene expression in mammary
      epithelial cells requires both physical and biochemical signal transduction.
AB  - Extracellular matrix (ECM) profoundly influences the growth and differentiation
      of the mammary gland epithelium, both in culture and in vivo. Utilizing a clonal
      population of mouse mammary epithelial cells that absolutely requires an
      exogenous ECM for function, we developed a rapid assay to study signal
      transduction by ECM. Two components of the cellular response to a basement
      membrane overlay that result in the expression of the milk protein beta-casein
      were defined. The first component of this response involves a rounding and
      clustering of the cells that can be physically mimicked by plating the cells on a
      nonadhesive substratum. The second component is biochemical in nature, and it is
      associated with beta 1 integrin clustering and increased tyrosine
      phosphorylation. The second component is initiated in a morphology-independent
      manner, but the proper translation of this biochemical signal into a functional
      response requires cell rounding and cell clustering. Thus, physical and
      biochemical signal transduction events contribute to the ECM-dependent regulation
      of tissue-specific gene expression in mouse mammary epithelial cells.

PMID- 7528921
TI  - Triple-strand-forming methylphosphonate oligodeoxynucleotides targeted to mRNA
      efficiently block protein synthesis.
AB  - Antisense oligonucleotides are ordinarily targeted to mRNA by double-stranded
      (Watson-Crick) base recognition but are seldom targeted by triple-stranded
      recognition. We report that certain all-purine methylphosphonate
      oligodeoxyribonucleotides (MPOs) form stable triple-stranded complexes with
      complementary (all-pyrimidine) RNA targets. Modified chloramphenicol
      acetyltransferase mRNA targets were prepared with complementary all-pyrimidine
      inserts (18-20 bp) located immediately 3' of the initiation codon. These modified
      chloramphenicol acetyltransferase mRNAs were used together with internal control
      (nontarget) mRNAs in a cell-free translation-arrest assay. Our data show that
      triple-strand-forming MPOs specifically inhibit protein synthesis in a
      concentration-dependent manner (> 90% at 1 microM). In addition, these MPOs
      specifically block reverse transcription in the region of their complementary
      polypyrimidine target sites.

PMID- 7528922
TI  - Short-lived complexes between myelin basic protein peptides and IAk.
AB  - Kinetic rate constants and the equilibrium dissociation constant have been
      determined for the reaction between an affinity-purified class II major
      histocompatibility complex molecule IAk and a myelin basic protein analogue
      peptide, fluorescein-labeled Ac(1-14)A4C15. Under the experimental conditions
      used, the lifetime of the peptide-free IAk molecule with respect to inactivation
      is 3.1 hr. The equilibrium dissociation constant, 3.3 +/- 1.7 microM, is
      determined from measurements of the kinetics of peptide inhibition of IAk
      inactivation. The measured peptide dissociation halftime is relatively short, 30
      min, and the deduced association rate is 100 M-1.s-1. The rate constants and the
      equilibrium constant are similar to those characteristic of kinetic intermediates
      in reactions of peptides and class II proteins that lead to long-lived terminal
      complexes.

PMID- 7528923
TI  - Beneficial effects and improved survival in rodent models of septic shock with S
      methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric
      oxide synthase.
AB  - Enhanced formation of nitric oxide (NO) by both the constitutive and the
      inducible isoforms of NO synthase (NOS) has been implicated in the
      pathophysiology of a variety of diseases, including circulatory shock. Non
      isoform-selective inhibition of NO formation, however, may lead to side effects
      by inhibiting the constitutive isoform of NOS and, thus, the various
      physiological actions of NO. S-Methylisothiourea sulfate (SMT) is at least 10- to
      30-fold more potent as an inhibitor of inducible NOS (iNOS) in immunostimulated
      cultured macrophages (EC50, 6 microM) and vascular smooth muscle cells (EC50, 2
      microM) than NG-methyl-L-arginine (MeArg) or any other NOS inhibitor yet known.
      The effect of SMT on iNOS activity can be reversed by excess L-arginine in a
      concentration-dependent manner. SMT (up to 1 mM) does not inhibit the activity of
      xanthine oxidase, diaphorase, lactate dehydrogenase, monoamine oxidase, catalase,
      cytochrome P450, or superoxide dismutase. SMT is equipotent with MeArg in
      inhibiting the endothelial, constitutive isoform of NOS in vitro and causes
      increases in blood pressure similar to those produced by MeArg in normal rats.
      SMT, however, dose-dependently reverses (0.01-3 mg/kg) the hypotension and the
      vascular hyporeactivity to vasoconstrictor agents caused by endotoxin [bacterial
      lipopolysaccharide (LPS), 10 mg/kg, i.v.] in anesthetized rats. Moreover,
      therapeutic administration of SMT (5 mg/kg, i.p., given 2 hr after LPS, 10 mg/kg,
      i.p.) attenuates the rises in plasma alanine and aspartate aminotransferases,
      bilirubin, and creatinine and also prevents hypocalcaemia when measured 6 hr
      after administration of LPS. SMT (1 mg/kg, i.p.) improves 24-hr survival of mice
      treated with a high dose of LPS (60 mg/kg, i.p.). Thus, SMT is a potent and
      selective inhibitor of iNOS and exerts beneficial effects in rodent models of
      septic shock. SMT, therefore, may have considerable value in the therapy of
      circulatory shock of various etiologies and other pathophysiological conditions
      associated with induction of iNOS.

PMID- 7528925
TI  - A predominant role of integrin alpha 4 in the spontaneous development of
      autoimmune diabetes in nonobese diabetic mice.
AB  - To elucidate the role of cell adhesion molecules in the pathogenesis of insulin
      dependent diabetes mellitus and to determine the predominant lymphocytic homing
      pathway(s) involved in the selective lymphocytic infiltration of pancreatic
      islets (insulitis), nonobese diabetic mice were treated with monoclonal
      antibodies specific for the L-selectin and integrin alpha 4 lymphocyte adhesion
      molecules. Treatment of neonatal mice with either anti-L-selectin or anti
      integrin alpha 4 monoclonal antibodies for the first 4 weeks of life led to a
      significant and long-term protection against spontaneous occurrence of insulitis
      and diabetes. The same treatment failed to inhibit lymphocytic infiltration of
      the salivary glands (sialadenitis). This tissue-specific inhibition of
      inflammation may be attributed to differences between the pancreas and salivary
      gland in their expression of endothelial ligands for L-selectin (peripheral
      vascular addressin) and for integrin alpha 4 (mucosal addressin cell adhesion
      molecule 1 and vascular cell adhesion molecule 1). Mucosal addressin cell
      adhesion molecule 1 is highly expressed by vessels within the inflamed islets but
      was not detected in the salivary glands. In contrast, peripheral vascular
      addressin- and vascular cell adhesion molecule 1-expressing vessels can be found
      in almost every area of inflammation within the salivary glands but are seen in
      only 40-50% of inflamed islets. Anti-L-selectin and anti-integrin alpha 4
      treatment had no demonstrable effect on anti-beta-cell autoimmunity or on the
      immune responses to foreign antigens. Therapeutic treatment with anti-L-selectin
      after the onset of insulitis from 10 to 14 weeks of age delayed the onset but
      failed to prevent spontaneous insulin-dependent diabetes mellitus, whereas anti
      integrin alpha 4 treatment resulted in a significant and long-lasting suppression
      of the disease. These data strongly suggest that integrin alpha 4 plays a
      prominent role in the spontaneous development of insulitis and diabetes in
      nonobese diabetic mice.

PMID- 7528924
TI  - Galanin antisense oligonucleotides reduce galanin levels in dorsal root ganglia
      and induce autotomy in rats after axotomy.
AB  - Antisense (AS) oligonucleotides (ONs) to galanin (GAL) were applied to the
      proximal end of a transected sciatic nerve, allowing their cellular uptake and
      transport into injured axons. GAL expression in dorsal root ganglia and self
      mutilation behavior (autotomy) were then studied. AS-ONs with phosphorothioate or
      allyl modifications significantly suppressed the axotomy-induced increase in GAL
      levels, as demonstrated by immunohistochemistry and exaggerated autotomy
      behavior, whereas no significant effect on GAL mRNA levels could be demonstrated
      with in situ hybridization. Allyl-ONs were more effective than phosphorothioate
      ONs. An AS-ON with three base mismatches did not induce any of the above effects.
      These results support the view that the inhibition of axotomy-induced GAL up
      regulation is related to autotomy.

PMID- 7528926
TI  - Keratinocyte expression of B7-1 in transgenic mice amplifies the primary immune
      response to cutaneous antigens.
AB  - Resting epidermal keratinocytes do not express B7-1 and other known CD28
      counterligands with costimulatory activity. The absence of these costimulators on
      keratinocytes correlates with their ability to preferentially induce T-cell
      anergy instead of T-cell activation. To test the hypothesis that keratinocytes
      expressing a CD28 counterligand would be more effective inducers of T-cell
      mediated immune responses in skin, we prepared transgenic mice in which
      expression of the B7-1 costimulator was targeted to basal keratinocytes by using
      the human K14 promoter. Keratinocytes from the K14/B7-1 transgenic line expressed
      high levels of surface B7-1. No spontaneous inflammatory changes were seen in
      transgenic skin, but epicutaneous application of contact sensitizers to these
      mice elicited a stronger primary ear swelling response than in controls. Sites of
      initial hapten application in transgenic mice also responded much more strongly
      to reapplication of hapten to a remote cutaneous site. Epidermal cell suspensions
      from transgenic mice contained normal numbers of Langerhans cells and dendritic
      epidermal T cells when analyzed by flow cytometry. Systemic treatment of the
      transgenic mice with interferon gamma induced high levels of class II major
      histocompatibility complex expression on keratinocytes but was not sufficient to
      initiate an inflammatory response. We conclude that the constitutive expression
      of the B7-1 molecule in vivo on a nonprofessional antigen-presenting cell is not
      by itself sufficient to trigger inflammatory changes, but B7-1 expression
      amplifies the host immune responses after exposure to nonself antigens presented
      by B7-1-expressing cells.

PMID- 7528927
TI  - The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane
      protein which is a subunit of 1,3-beta-D-glucan synthase.
AB  - In Saccharomyces cerevisiae, mutations in FKS1 confer hypersensitivity to the
      immunosuppressants FK506 and cyclosporin A, while mutations in ETG1 confer
      resistance to the cell-wall-active echinocandins (inhibitors of 1,3-beta-D-glucan
      synthase) and, in some cases, concomitant hypersensitivity to the chitin synthase
      inhibitor nikkomycin Z. The FKS1 and ETG1 genes were cloned by complementation of
      these phenotypes and were found to be identical. Disruption of the gene results
      in (i) a pronounced slow-growth phenotype, (ii) hypersensitivity to FK506 and
      cyclosporin A, (iii) a slight increase in sensitivity to echinocandin, and (iv) a
      significant reduction in 1,3-beta-D-glucan synthase activity in vitro. The
      nucleotide sequence encodes a 215-kDa polypeptide predicted to be an integral
      membrane protein with 16 transmembrane helices, consistent with previous
      observations that the etg1-1 mutation results in echinocandin-resistant glucan
      synthase activity associated with the nonextractable membrane fraction of the
      enzyme. These results suggest that FKS1 encodes a subunit of 1,3-beta-D-glucan
      synthase. The residual activity present in the disruption mutant, the
      nonessential nature of the gene, and results of Southern blot hybridization
      analysis point to the existence of a glucan synthase isozyme.

PMID- 7528928
TI  - Cholangiocytes express the aquaporin CHIP and transport water via a channel
      mediated mechanism.
AB  - Cholangiocytes line the intrahepatic bile ducts and regulate salt and water
      secretion during bile formation, but the mechanism(s) regulating ductal water
      movement remains obscure. A water-selective channel, the aquaporin CHIP, was
      recently described in several epithelia, so we tested the hypothesis that osmotic
      water movement by cholangiocytes is mediated by CHIP. Isolated rodent
      cholangiocytes showed a rapid increase in volume in the presence of hypotonic
      extracellular buffers; the ratio of osmotic to diffusional permeability
      coefficients was > 10. The osmotically induced increase in cholangiocyte volume
      was inversely proportional to buffer osmolality, independent of temperature, and
      reversibly blocked by HgCl2. Also, the luminal area of isolated, enclosed bile
      duct units increased after exposure to hypotonic buffer and was reversibly
      inhibited by HgCl2. RNase protection assays, anti-CHIP immunoblots, and
      immunocytochemistry confirmed that CHIP transcript and protein were present in
      isolated cholangiocytes but not in hepatocytes. These results demonstrate that
      (i) isolated cholangiocytes and intact, polarized bile duct units manifest rapid,
      mercury-sensitive increases in cell size and luminal area, respectively, in
      response to osmotic gradients and (ii) isolated cholangiocytes express aquaporin
      CHIP at both the mRNA and the protein level. The data implicate aquaporin water
      channels in the transcellular movement of water across cholangiocytes lining
      intrahepatic bile ducts and provide a plausible molecular explanation for ductal
      water secretion.

PMID- 7528930
TI  - Enrichment for RNA molecules that bind a Diels-Alder transition state analog.
AB  - RNA molecules that bind a transition state analog for a Diels-Alder reaction (Kd
      = 0.35 +/- 0.05 mM) were isolated from a starting pool of approximately 10(14)
      sequences by affinity chromatography. After the initial rise and plateau of the
      amount of RNA that eluted with soluble analog, a step gradient elution was used
      to further enrich the pool for sequences with higher affinities for the target.
      To our knowledge, the isolation of RNA molecules that bind either a nonplanar or
      a hydrophobic ligand has not been reported previously. A conserved nucleotide
      sequence and secondary structure present in many of the RNA molecules are
      necessary but not sufficient for binding the analog. No catalysts of the targeted
      Diels-Alder reaction were found among the binders. The absence of catalysis
      contrasts with previous successful experiments with antibodies and suggests that
      other strategies may be needed to identify oligonucleotides with diverse
      catalytic activities.

PMID- 7528929
TI  - Stable expression of a functional GluR6 homomeric glutamate receptor channel in
      mammalian cells.
AB  - This study demonstrates the stable expression of a functional ionotropic
      glutamate receptor in a mammalian cell line of non-neuronal origin. The kainate
      selective glutamate receptor GluR6 was constitutively expressed under the control
      of a metallothionein promoter. Clones were isolated expressing approximately 3
      pmol of receptor per mg of protein. Functionality of the recombinant GluR6 was
      demonstrated both by electrophysiology and by Ca2+ imaging. Application of
      kainate to the GluR6-transfected cells activated an inward current response at a
      holding potential of -60 mV. The kainate concentration needed to evoke 50% of the
      maximal response (EC50) was calculated to be 0.82 +/- 0.39 microM. The current
      voltage relationship was found to be almost linear, with a reversal potential of 
      2.5 +/- 4.8 mV. Application of kainate also resulted in an increase in the
      intracellular Ca2+ concentration measured by Ca2+ imaging. The pharmacological
      profile of [3H]kainate binding to the recombinant GluR6 resembled the high
      affinity [3H]kainate binding sites in rat brain, showing high affinity for
      domoate (Ki = 5.1 +/- 3.0 nM) and kainate (Kd = 12.9 +/- 2.4 nM). No decrease in
      GluR6 expression level was observed over > 75 passages of the transfected cells.
      When domoate, a slowly desensitizing GluR6 agonist, was included in the growth
      medium for 3 weeks, the number of GluR6 binding sites decreased by 30%,
      indicating the importance of complete channel closure for stable expression.

PMID- 7528931
TI  - Molecular characterization of an aquaporin cDNA from brain: candidate
      osmoreceptor and regulator of water balance.
AB  - The aquaporins transport water through membranes of numerous tissues, but the
      molecular mechanisms for sensing changes in extracellular osmolality and
      regulating water balance in brain are unknown. We have isolated a brain aquaporin
      by homology cloning. Like aquaporin 1 (AQP1, also known as CHIP, channel-forming
      integral membrane protein of 28 kDa), the deduced polypeptide has six putative
      transmembrane domains but lacks cysteines at the known mercury-sensitive sites.
      Two initiation sites were identified encoding polypeptides of 301 and 323 amino
      acids; expression of each in Xenopus oocytes conferred a 20-fold increase in
      osmotic water permeability not blocked by 1 mM HgCl2, even after substitution of
      cysteine at the predicted mercury-sensitive site. Northern analysis and RNase
      protection demonstrated the mRNA to be abundant in mature rat brain but only
      weakly detectable in eye, kidney, intestine, and lung. In situ hybridization of
      brain localized the mRNA to ependymal cells lining the aqueduct, glial cells
      forming the edge of the cerebral cortex and brainstem, vasopressin-secretory
      neurons in supraoptic and paraventricular nuclei of hypothalamus, and Purkinje
      cells of cerebellum. Its distinctive expression pattern implicates this fourth
      mammalian member of the aquaporin water channel family (designated gene symbol,
      AQP4) as the osmoreceptor which regulates body water balance and mediates water
      flow within the central nervous system.

PMID- 7528933
TI  - Chemotherapy for advanced non-small-cell lung cancer.

PMID- 7528932
TI  - Comparison of the electrophysiological effects of S49, CSH087 and CSH068 in rat
      ventricular cells.
AB  - S49, CSH087 and CSH068 are aporphine alkaloids and are synthesized from vanillin.
      In the present study, the effects of these compounds on the action potential and
      membrane currents of rat ventricular cells were examined by using the whole cell
      recording technique with single suction pipettes. At a stimulation frequency of
      0.1 Hz, S49 (1.5 microM), CSH087 (3 microM) and CSH068 (3 microM) could prolong
      the action potential durations (APD50 and APD90). Voltage clamp studies revealed
      inhibition of the transient outward currents by S49, CSH087 and CSH068 with KD of
      2.0, 1.8 and 5.2 microM, respectively, but a lack of enhancement of calcium
      influx. Therefore, the inhibition of the potassium conductance may explain the
      prolongation of APD induced by these compounds. In contrast, the late potassium
      outward current was more resistant to CSH087 and S49, but was blocked by CSH068
      with a KD of 6.4 microM. The sodium inward current (INa) also was inhibited by
      S49, CSH087 and CSH068 in a dose-dependent manner with KD of 1.2, 6.8 and 7.5
      microM, respectively (at a holding potential of -80 mV). The inhibition of INa)
      was enhanced at a less negative holding potential. The voltage-dependent
      inhibition of INa was associated with the shift of the INa availability curve to
      more negative potentials. These results indicate that these compounds have high
      affinity for inactivated Na+ channels. A twin-pulse experiment revealed that
      these compounds increased the recovery time constant of INa. The potency for the
      shift of the INa availability curve and the retardation of INa recovery from
      inactivation were S49 > CSH087 and CSH)68.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528935
TI  - Pulmonary toxicity of chemotherapy and GM-CSF.

PMID- 7528934
TI  - Identification of M. tuberculosis ribosomal RNA in mouthwash samples from
      patients with tuberculosis.
AB  - It is often not possible to obtain satisfactory sputum samples from patients
      suspected of having pulmonary tuberculosis. In this study, we asked whether it
      was possible to identify M. tuberculosis ribosomal RNA (rRNA) in mouthwash
      samples, and in a prospective clinical study, whether the presence of this rRNA
      correlated with clinical M. tuberculosis infection. Using a combination of
      reverse transcriptase and polymerase chain reaction amplification, it was
      possible to identify M. tuberculosis rRNA in mouthwash samples. M. tuberculosis
      rRNA was identified in mouthwash samples from patients with active tuberculosis
      more commonly than in samples from control subjects (P < 0.05). The test was
      positive in four of ten patients with active pulmonary tuberculosis, one of eight
      contacts, none of eight past cases of tuberculosis, two of eight patients with
      other diagnosis and one of five healthy volunteers. M. tuberculosis rRNA was
      identified in sputum from four of eight patients and in bronchoscopy trap samples
      from four of five patients with active tuberculosis. However, one of ten sputum
      samples and two of five bronchoscopy samples from subjects with a clinical
      diagnosis other than active tuberculosis were positive. These results indicate
      that although it is technically possible to identify M. tuberculosis on the basis
      of the presence of rRNA in mouthwash samples, the poor sensitivity and
      specificity of the technique suggest that it is unlikely to be useful clinically.

PMID- 7528936
TI  - [Hepatitis C virus infection in patients with porphyria].
AB  - Hepatitis C virus antibodies were studied in sera coming from 39 patients with
      porphyria (cutanea tarda in 17, variegate in 8, intermittent acute in 4,
      coproporphyria in 2 and protoporphyria in 8). Nine of 17 patients with porphyria
      cutanea tarda had positive antibodies, but none of the patients with other types
      of porphyria. All subjects with porphyria cutanea tarda had histological or
      laboratory liver abnormalities. There was no relationship between the presence of
      antibodies and frequency of alcoholism, diabetes, or carbohydrate intolerance.
      Family background of porphyria was significantly less frequent among patients
      with positive hepatitis C virus antibodies. In 13 patients, a liver biopsy was
      performed, always showing signs of chronic hepatitis, whose magnitude was higher
      in those with positive antibodies. It is concluded that, as reported previously,
      hepatitis C virus may be an activating factor for porphyria cutanea tarda or may
      potentiate its accompanying liver disease.

PMID- 7528938
TI  - [The prostate. Surgery of prostate adenoma].

PMID- 7528939
TI  - Effect of nasal spray, positional therapy, and the combination thereof in the
      asymptomatic snorer.
AB  - The benefits of using a nasal decongestant, sleeping on one's side and the
      combination thereof were studied in 20 asymptomatic male snorers. Both the apnea
      hypopnea index (AHI) and snoring were evaluated. Four consecutive nocturnal
      polysomnographic studies were done. Night 1 was a control; the other 3 nights
      were randomly assigned to nasal decongestant, best sleeping position and a
      combination of the two. Results were calculated based on sleep period time. The
      mean control AHI +/- the standard error of the mean (SEM) was 17.5 +/- 6.5. AHI
      improved to 14.1 +/- 6.3 with sleep in the best position (p = 0.03). The AHI also
      improved to 13.2 +/- 6.04 with both nasal decongestant and position (p = 0.0012).
      Using nasal decongestant alone, the mean AHI was 18.1 +/- 6.3 (p = 0.765). During
      the control night, the mean number of snores/hour +/- SEM was 356 +/- 46.0. Using
      nasal decongestant alone, the mean number of snores was 381 +/- 50.4 (p = 0.50).
      With position alone, the mean number of snores was 356 +/- 46.0 (p = 0.8). Using
      the combination of nasal decongestant and position, mean snores were 352 +/- 48.9
      (p = 0.91). In conclusion, a statistically significant improvement in AHI was
      produced using the general measures of altering the position of the body during
      sleep and by the combination of nasal decongestant and positional change. There
      was no significant change in snoring using any of these general measures.

PMID- 7528940
TI  - Functional isolation and characterization of human hematopoietic stem cells.
AB  - Hematopoietic cells differentiate in steps marked by the acquisition or loss of
      specific phenotypic characteristics. Human bone marrow cells that were responsive
      to the early-acting cytokines Kit ligand and interleukin-3 were forced to a
      metabolic death. The subfraction remaining represented 1 in 10(5) bone marrow
      mononuclear cells, were determined to be quiescent by cell cycle analysis, and
      had a stem cell immunophenotype. The cells were highly enriched for long-term
      culture-initiating cells, were capable of secondary colony formation, and
      produced both myeloid and lymphoid progeny. Thus, this technically simple
      strategy led to the efficient purification of cells with characteristics of
      hematopoietic stem cells.

PMID- 7528937
TI  - [Microwave transurethral thermotherapy in the treatment of prostatic adenoma].
AB  - We report 195 patients with prostatic adenoma treated with microwave
      transurethral thermotherapy. All patients were initially subjected to a clinical
      assessment including Madsen-Iversen symptom score, digital rectal examination,
      measurement of urine flow rate and residual urine volume, transrectal prostatic
      ultrasound examination and blood prostate specific antigen determination. A
      prostatron machine was used, installing an urethral probe under local anesthesia.
      Endourethral and rectal temperatures were simultaneously measured and the
      procedure was controlled by a special software. The treatment was performed in an
      outpatient basis with a single procedures that lasted 60 min. Of 31 patients with
      chronic urinary retention, 28 were left voiding spontaneously, without urethral
      catheters and 84% of 164 symptomatic patients were relieved. No complications
      occurred, although 31.1% of patients has a transitory urinary retention after the
      procedure. It is concluded that microwave thermotherapy is a good therapeutic
      alternative for prostatic adenoma.

PMID- 7528941
TI  - Association of protein kinase A and protein phosphatase 2B with a common
      anchoring protein.
AB  - Specificity of protein kinases and phosphatases may be achieved through
      compartmentalization with preferred substrates. In neurons, adenosine 3', 5'
      monophosphate (cAMP)-dependent protein kinase (PKA) is localized at postsynaptic
      densities by association of its regulatory subunit with an A kinase anchor
      protein, AKAP79. Interaction cloning experiments demonstrated that AKAP79 also
      binds protein phosphatase 2B, or calcineurin (CaN). A ternary complex of PKA,
      AKAP, and CaN was isolated from bovine brain, and colocalization of the kinase
      and the phosphatase was established in neurites of cultured hippocampal neurons.
      The putative CaN-binding domain of AKAP79 is similar to that of the immunophilin
      FKBP-12, and AKAP79 inhibited CaN phosphatase activity. These results suggest
      that both PKA and CaN are targeted to subcellular sites by association with a
      common anchor protein and thereby regulate the phosphorylation state of key
      neuronal substrates.

PMID- 7528944
TI  - [A modeling studio].

PMID- 7528943
TI  - Identification of bases in 16S rRNA essential for tRNA binding at the 30S
      ribosomal P site.
AB  - Previous studies suggest that the mechanism of action of the ribosome in
      translation involves crucial transfer RNA (tRNA)-ribosomal RNA (rRNA)
      interactions. Here, a selection scheme was developed to identify bases in 16S
      rRNA that are essential for tRNA binding to the P site of the small (30S)
      ribosomal subunit. Modification of the N-1 and N-2 positions of 2-methylguanine
      966 and of the N-7 position of guanine 1401 interfered with messenger RNA (mRNA)
      dependent binding of tRNA to the P site. Modification of the same positions as
      well as of the N-1 and N-2 positions of guanine 926 interfered with mRNA
      independent binding of tRNA at high magnesium ion concentration. These results
      suggest that these three bases are involved in intermolecular contacts between
      ribosomes and tRNA.

PMID- 7528945
TI  - Genetic predisposition of autoimmune disease and B-cell chronic lymphocytic
      leukemia (B-CLL).
AB  - Autoimmune disease is a polygenic disease in which various genetic factors play
      crucial roles. The familial clustering and the association of HLA haplotypes have
      been well-recognized. There is a close association between chronic lymphocytic
      leukemia (CLL) and autoimmune disease. Like autoimmune diseases, CLL is the type
      of leukemia most often occurring among close relatives. The patients with CLL
      frequently share common HLA haplotypes with relatives with autoimmune disease. As
      the majority of CLL is of CD5+ B-cell type, and as CD5+ B cells are suggested to
      be involved in autoimmunity, certain regulatory abnormalities in the
      proliferation and differentiation of CD5 B cells may be involved in both B-CLL
      and autoimmune disease. I discuss here the possibility that different, but
      related, MHC haplotypes would predispose either to autoimmune disease or to B
      CLL, based on our findings obtained from MHC (H-2)-congenic New Zealand mouse
      strains.

PMID- 7528942
TI  - Footprint analysis of replicating murine leukemia virus reverse transcriptase.
AB  - Replication complexes that contained either murine leukemia virus reverse
      transcriptase (MLV RT) or a variant reverse transcriptase without a ribonuclease
      (RNase) H domain (delta RH MLV RT) were visualized by enzymatic footprinting.
      Wild-type MLV RT protected template nucleotides +6 to -27, and primer nucleotides
      -1 to -26 of primers that had first been extended by one or four nucleotides.
      Although it catalyzed DNA synthesis, delta RH MLV RT stably bound template-primer
      only under conditions of reduced ionic strength and protected the duplex portion
      only as far as position -15. Despite altered hydrolysis profiles, both enzymes
      covered primarily the template-primer duplex, contradicting recent predictions
      based on the structure of rat DNA polymerase beta.

PMID- 7528946
TI  - Possible mechanisms of autoantibody production and the connection of viral
      infections in human autoimmune diseases.
AB  - The presence of autoantibodies is a characteristic phenomenon in an autoimmune
      disease. In order to investigate the mechanisms of the autoantibody production,
      we have performed epitope mappings of the autoantigens. It thus was found that
      there were multiple epitopes on an autoantigen molecule, and a serum from a
      patient with an autoimmune disease usually recognizes these multiple epitopes
      simultaneously, suggesting that autoantibodies are ultimately produced by an
      antigen-driven mechanism. However, other evidence suggests that tolerance to a
      self antigen is rather tightly maintained and a simple antigen-driven mechanism
      cannot easily take place. Based on the results of epitope mappings, it appears
      that there is a major or a usually recognized epitope on almost every autoantigen
      molecule. Some patients only recognize this epitope. It is unlikely that only a
      single epitope can be recognized if a large molecule is immunized to the host.
      Therefore, the recognition of this universal epitope may play some roles in the
      induction of the autoantibody production. In fact, some of these epitopes have
      sequences homologous to those of viral proteins. Thus, it is possible that an
      immune response to a certain virus might induce by molecular mimicry the
      recognition of an autoantigen. Possible mechanisms following this molecular
      mimicry that may induce antigen-driven autoantibody production are discussed.

PMID- 7528947
TI  - Physiology and pathology of host immune responses to exogenous and endogenous
      murine retroviruses--from gene fragments to epitopes.
AB  - Spontaneous and induced immunity against exogenous Friend murine leukemia
      retrovirus infection is controlled by four H-2-linked host genes and a single non
      H-2 gene. Recognition of the envelope glycoprotein gp70 of Friend virus by helper
      T cells is restricted by Ab and hybrid Eb/k(d) class II MHC molecules. By
      expressing portions of the env gene and by utilizing synthetic oligopeptides, an
      Ab-restricted and a hybrid Eb/d-restricted helper T cell epitopes were identified
      in the N-and C-terminal portions of gp70, respectively. These epitopes differ in
      their amino acid sequences from the previously reported endogenous retroviral
      peptides naturally presented by mouse MHC class II molecules. Possible roles of
      recombinant polytropic viruses in the induction of autoimmune responses against
      endogenous retroviral antigens are also discussed.

PMID- 7528948
TI  - The contribution of reduced functioning mass to chronic kidney allograft
      dysfunction in rats.
AB  - Chronic renal allograft dysfunction may become manifest months or years after
      transplantation by progressive functional deterioration associated with
      morphological changes that include vascular obliteration, glomerular sclerosis,
      tubular atrophy, and interstitial fibrosis. Two hypotheses have evolved to
      explain the etiology of this process, usually described as "chronic rejection:"
      first, that it is primarily an antigen-dependent phenomenon influenced by
      continuing host alloresponsiveness; second, that nonimmunological, alloantigen
      independent factors contribute to the progressive changes. Using an established
      model of chronic rejection of kidney transplants in rats in which the lesions
      progress relentlessly over time, we have determined the long-term effects of
      superimposing renal mass reduction on the indices of progressive allograft
      injury. Increasing proteinuria, a reproducible index of kidney graft dysfunction,
      developed after 12 weeks in all recipients of intact allografts, but was
      accelerated in kidneys with reduced mass, regardless of whether the organ was
      allogeneic or isogeneic. The coincident infiltration of macrophages and
      expression of cytokines and growth factors were associated with the development
      of glomerular sclerosis and interstitial fibrosis; such functional and
      morphological alterations occurred in an accelerated manner in all reduced-mass
      kidney allografts and isografts. Conversely, intact allografts in recipients also
      bearing a retained native kidney never manifested any chronic changes throughout
      the entire follow-up period. These findings emphasize the role of alloantigen
      independent factors, particularly reduced renal mass, in the multi-factorial
      etiology of "chronic rejection" of kidney transplants.

PMID- 7528949
TI  - Fibrinolytic activity during orthotopic liver transplantation with and without
      aprotinin.
AB  - Hyperfibrinolysis during orthotopic liver transplantation (OLT) has been
      attributed to high plasma levels of tissue plasminogen activator (t-PA). This
      study investigated the contribution of urokinase plasminogen activator (u-PA) to
      hyperfibrinolysis and the effects of high-dose perioperative aprotinin (Trasylol)
      on fibrinolytic activation. Plasma samples were collected before, during, and
      after OLT in fifty five patients receiving either high dose aprotinin or placebo
      in a randomized double-blind trial. t-PA antigen and u-PA antigen and activity
      levels were increased preoperatively compared with normal controls (P < 0.05).
      Hyperfibrinolysis was seen during the anhepatic phase as shown by shortened
      euglobulin clot lysis times (ECLT) and an increase in D-dimer titers. t-PA levels
      peaked on reperfusion and fell at the end of the operation, and u-PA levels did
      not increase during OLT, but showed a decrease at the end of the operation. With
      aprotinin treatment, t-PA levels were lower on graft reperfusion than the placebo
      group (P < 0.05), but there was no difference in u-PA antigen or activity levels
      between groups. Fibrinolytic inhibition during OLT by aprotinin was demonstrated
      by prolonged ECLT (P < 0.05), reduced D-dimer levels (P < 0.05), and an increase
      in antiplasmin activity (P < 0.05). This study showed that the main
      antifibrinolytic action of aprotinin is as an antiplasmin agent with some effect
      on t-PA-but not u-PA-mediated fibrinolysis.

PMID- 7528950
TI  - Divergent patterns of ELAM-1, ICAM-1, and VCAM-1 expression on cytomegalovirus
      infected endothelial cells.
AB  - Endothelial cells, one of several in vivo host cells for cytomegalovirus (CMV),
      participate in solid organ allograft rejection in part through the expression of
      leukocyte adhesion molecules. The hypothesis that CMV infection alters the
      constitutive and induced expression of ELAM-1, ICAM-1, and VCAM-1 on infected
      human umbilical vein endothelial cells (HUVECs) was examined. HUVECs were
      infected with an endothelial cell-propagated strain of CMV (VHL/E) for various
      periods, treated with tumor necrosis factor-alpha (TNF alpha), and examined by
      flow cytometry or immunohistochemically dual-labeled with monoclonal antibodies
      to CMV immediate early nuclear protein and ELAM-1, ICAM-1, or VCAM-1. Neither
      ELAM-1 nor VCAM-1 was induced on CMV-infected HUVECs, and treatment with TNF
      alpha treatment did not result in their induction. In contrast, ICAM-1 was
      induced on infected HUVECs by 24 hr postinfection. Endothelial ICAM-1 induction
      may represent a mechanism by which CMV infection exacerbates the recipient
      cellular immune response to allografts.

PMID- 7528951
TI  - Localization of inducible nitric oxide synthase in acute renal allograft
      rejection in the rat.
AB  - There is increasing evidence for a role for nitric oxide (NO) in the alloimmune
      response and induction of NO synthesis occurs during allograft rejection. The aim
      of this study was to investigate the source of NO synthesis in rejecting
      allografts. Localization of inducible nitric oxide synthase (iNOS) was studied by
      immunohistochemistry, in a rat model of acute renal allograft rejection, in
      unmodified Lewis recipients in which rejection is complete 7 days after
      transplantation of F1 hybrid Lewis-Brown Norway kidneys. High levels of iNOS
      expression were found in infiltrating mononuclear cells in glomeruli and
      interstitium of rejecting kidneys; there was no expression in parenchymal renal
      cells, or in control isografts of either rat strain. Expression of iNOS in the
      cortex was present from 4 to 6 days posttransplantation, and had declined by the
      7th day, where expression was principally in the medulla. The pattern of iNOS
      staining was similar to ED1 staining, a marker for rat macrophages. These
      findings suggest that infiltrating macrophages in the graft reaction are a
      prominent source of NO; this iNOS expression supports a role for NO in the
      modulation of local allogeneic responses, and possibly as a mediator of cytotoxic
      graft damage.

PMID- 7528952
TI  - Albuminuria as an indicator of rejection in bladder-drained pancreas allografts.

PMID- 7528953
TI  - Functional expression of human CD59 in transgenic mice.

PMID- 7528955
TI  - Development of a sandwich immunoassay for the detection of soluble ovine IL-2R
      alpha chain.
AB  - Following T cell activation with antigen or mitogens, there is an up-regulation
      of interleukin-2 receptor alpha (IL-2R alpha) chain expression. A high proportion
      of the IL-2R alpha chain is shed from the surface of the T cell in a soluble form
      following proteolytic cleavage, and thus determination of soluble IL-2R alpha
      (sIL-2R alpha) chain is an excellent measure of lymphocyte activation. A sandwich
      immunoassay for the detection of ovine sIL-2R alpha chain has been developed.
      Three monoclonal antibodies (mAbs) with specificity for the IL-2R alpha chain,
      demonstrated by immunoprecipitation of a 50 kDa protein from an ovine IL-2R alpha
      chain cDNA transfected Chinese hamster ovarian (CHO IL-2R) cell line, were
      analysed for additive and competitive binding to CHO IL-2R cells and Concanavalin
      A (Con A) activated ovine lymphocytes, respectively. Two non-competitive ovine IL
      2R alpha chain specific mAbs were then used in a sandwich immunoassay to detect
      native sIL-2R alpha chain in the supernatant (SN) of Con A activated ovine
      lymphocytes and recombinant sIL-2R alpha chain in the SN of CHO IL-2R cells.
      Soluble IL-2R alpha chain could also be detected in complex biological fluid. In
      the efferent lymph of a cannulated ovine popliteal lymph node (LN), an increase
      in the level of sIL-2R alpha chain following local alloantigen LN activation was
      observed. This increase correlated with an increase in the output of activated T
      cell blasts.

PMID- 7528954
TI  - A nonradioactive assay system for screening for inhibitors of reverse
      transcriptase.

PMID- 7528956
TI  - The national home and hospice care survey: 1992 summary.

PMID- 7528957
TI  - Pharmacotherapy for benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia is a benign neoplasm of the prostate seen in men of
      advancing age. Microscopic evidence of the disorder is seen in about 70% of men
      by 70 years of age, whereas symptoms requiring some form of surgical intervention
      occur in 30% of men during their lifetime. Although the exact cause of benign
      prostatic hyperplasia is not clear, it is well recognized that high levels of
      intraprostatic androgens are required for the maintenance of prostatic growth. In
      recent years, extensive surveys of patients undergoing transurethral resection of
      the prostate reveal an 18% incidence of morbidity that has essentially not
      changed in the past 30 years. This procedure is also the second highest
      reimbursed surgical therapy under Medicare. These findings have resulted in an
      intensive search for alternative therapies for prostatic hyperplasia. An
      alternative that has now been well defined is the use of alpha-adrenergic
      blockers to relax the prostatic urethra. This is based on findings that a major
      component of benign prostatic hyperplasia symptoms is spasm of the prostatic
      urethra and bladder neck, which is mediated by the alpha-adrenergic nerves. A
      second approach is to block androgens involved in maintaining prostate growth.
      Several such drugs are now available for clinical use, and we discuss their side
      effects and use. We also include the newer recommendations on evaluating benign
      prostatic hyperplasia that are cost-effective yet comprehensive.

PMID- 7528958
TI  - Pharmacologic management of benign prostatic hyperplasia--changing times.

PMID- 7528959
TI  - [Abnormal endothelium-mediated regulation of vascular tone in arteriosclerosis].
AB  - Knowledge regarding the endothelial-derived relaxing factor (EDRF) has
      substantially increased over recent years. The chemical identification of EDRF as
      nitric oxide (NO) and the discovery of the NO-pathway started an exciting
      research field with new insights into the regulation of many biologic processes.
      Concerning regulation of the vascular tone, EDRF(NO) is one of the most potent
      relaxant substances known; in addition, EDRF(NO) is a potent inhibitor of
      platelet adhesion and aggregation and leukocyte adhesion to the vascular wall;
      furthermore, EDRF(NO) is probably an inhibitor of smooth muscle cell
      proliferation. This profile of EDRF(NO) may be an important part of the anti
      arteriosclerotic function of intact endothelial cells. In animal models of
      hypercholesterolemia and in patients with hypercholesterolemia and/or
      arteriosclerosis, the EDRF(NO) mechanism is impaired or almost abolished (=
      endothelial dysfunction). The reason for this abnormal endothelial function is
      not fully understood and may be multifactorial; it has been suggested that this
      endothelial dysfunction is due to an accelerated breakdown of EDRF(NO) by
      oxidized low density lipoprotein and/or oxygen derived free radicals. In
      addition, there may be an increased release of vasoconstrictive substances, e.g.,
      endothelin-1, from endothelial cells which may override the relaxant effects of
      EDRF (NO). This abnormal function of the endothelium (in terms of the EDRF(NO)
      mechanism) appears to be reversible in animal models and in patients with
      hypercholesterolemia, and is accomplished by normalizing plasma cholesterol
      levels.

PMID- 7528960
TI  - [Hot flashes after orchiectomy in treatment of prostate cancer-- a serious side
      effect].
AB  - Orchiectomy is a frequently performed therapy for prostatic carcinoma in elderly
      men. A so far widely neglected side-effect is the occurrence of hot flushes. They
      considerably decrease the quality of life of a large number of the patients who
      often are in a palliative situation and handicapped by other diseases.
      Therapeutic options are widely unknown. Therefore, the patients often consult
      their doctors in vain. In a study with 32 patients clinical appearance of hot
      flushes and their effects on the patient's quality of life were analyzed. 69% of
      patients with a mean age of 75 years experienced hot flushes, whereas 31% of
      patients with a mean age of 80 years had not been bothered by hot flushes.
      Possible therapeutic options are presented and discussed. Ciproteronacetate seems
      to be the most effective therapy with the least side-effects (9).

PMID- 7528961
TI  - [The effect of a lipoxygenase inhibitor on the modulation of cholinoreceptor
      plasticity by 15-HETE].
AB  - The role of acyclic eicosanoids in the modulation of the plasticity of somatic
      cholinoreceptors, due to 15(S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid (15
      HETE), was studied in identified neurons of Helix lucorum. Lipoxygenase
      inhibitor, nordihydroguaiaretic acid blocks the effects of 15-HETE on the
      extinction of the inward current, evoked by the rhythmic application of
      acetylcholine on the neuron. The conclusion was reached that the short-latency
      effect of 15-HETE, on the plasticity of cholinoreceptors is due to the inhibition
      it produces on the 5-lipoxygenase. This effect leads to a lowering on the level
      of acyclic eicosanoids which are formed by the action of this enzyme. The
      potentiation of the effect of the acyclic eicosanoids, whose synthesis is renewed
      in the second phase, is a plausible explanation of the long-latency modulatory
      effect of 15-HETE.

PMID- 7528963
TI  - Cytokines and the liver in health and disease. Effects on liver metabolism and
      fibrogenesis.
AB  - The liver is the largest organ in the body providing a large number of essential
      functions for the organism. It is the center for the metabolism of nutrients and
      drugs, and plays a key role in the unspecific immune system by harbouring Kupfer
      cells, the majority of all macrophages. The liver is the main site for the
      synthesis of many different metabolites and releases most of the plasma proteins.
      All these functions of the liver must be coordinated and regulated in response to
      metabolic changes and minor or major injuries. This is accomplished by
      metabolites, the autonomous nerve system, the endocrine system and by cytokines,
      which form a complex network of mediator molecules. Cytokines modulate liver
      metabolism in many ways. Synthesis of acute phase proteins is regulated by
      cytokines such as IL-1, IL-6, IL-11, leukemia inhibitory factor, TNF,
      transforming growth factor beta, epidermal growth factor, and ciliary derived
      neurotropic factor, which interact synergistically with corticosteroids and
      insulin. Hepatic lipid metabolism and hepatic carbohydrate metabolism are also
      regulated by cytokines and by classical hormones. Cytokines play an important
      role in the pathogenesis of liver diseases and liver fibrosis, which is the
      common morphological reaction after chronic injury of the liver. An uncontrolled
      production of extracellular matrix and its impaired degradation destroy the
      architecture of the liver and its function. Fat-storing cells (Ito cells,
      lipocytes, perisinusoidal cells) are the major source of extracellular matrix in
      the liver. They are activated to proliferate or to produce extracellular matrix
      compounds by cytokines like transforming growth factor beta, and platelet derived
      growth factor (PDGF). Interferon gamma and alpha inhibit this activation.
      Modulation of fibrogenesis by these cytokines may be helpful for future treatment
      of liver fibrosis.

PMID- 7528964
TI  - Spacio-temporal progression of demyelination in twitcher mouse: with clinico
      pathological correlation.
AB  - The twitcher (twi/twi) is an authentic murine model of human globoid cell
      leukodystrophy (GLD), caused by a deficiency of galactosylceramidase. Similar to
      human GLD, the twitcher shows progressive deterioration of neurological function
      and its neuropathology is characterized by a collection of periodic acid-Schift
      stain (PAS)-positive macrophages in the areas of demyelination. However, there
      are some differences in the clinico-pathological aspects between human and murine
      GLD. We investigated the spacio-temporal progression of neuropathology in the
      twitcher from postnatal day (PND) 10 to 45. No clinical symptoms or
      neuropathological changes were apparent in twi/twi until PND 15. Generally,
      infiltration of macrophages, concomitant with myelin degeneration, was recognized
      in the cerebellar white matter and the brain stem after PND 20, then in cerebral
      white matter after PND 25, and in cerebral and cerebellar gray matter after PND
      30. The demyelination was very severe in the radix of the 8th and the 5th cranial
      nerves. The neurological symptoms such as tremor, spasticity and cranial nerve
      dysfunction were well correlated with the progression of pathological changes.
      Demyelination progressed in an orderly fashion such that myelin degeneration
      began 10 to 20 days after the commencement of myelination in any of the given
      nerve fiber tracts. This suggests that there are no significant differences in
      the metabolism of galactocerebroside in the myelin and myelin-forming cells in
      individual nerve fiber tracts throughout the murine brain. Over-expression of
      glial fibrillary acidic protein was already present before the initiation of
      obvious demyelination.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528966
TI  - Repeatable measurement of local and zonal GFR in the rat kidney with aprotinin.
AB  - The basic polypeptide aprotinin (Ap), mol. wt 6513, is freely filtered in
      glomeruli and completely reabsorbed by the proximal tubules. Cellular processing
      is slow with return to plasma of breakdown products beginning after 20-30 min.
      When corrected for Gibbs-Donnan distribution of Ap between glomerular filtrate
      and plasma (i.e. 0.65 at a plasma protein concentration of 50 mg ml-1), the renal
      clearance of [125I]Ap, estimated as the ratio of kidney uptake and integrated non
      protein bound plasma 125I concentration, equals that of [51Cr]EDTA (urine +
      kidney content). Zonal GFR per gram tissue was obtained from uptake in three to
      six samples from outer and inner cortex (OC, IC) and the cortico-medullary border
      zone, 5-30 min after i.v. injection in rats. Control GFR in OC was 2.05 (SD 0.39)
      ml g-1 min-1 and the IC/OC ratio 0.66 (SD 0.14). Repeated local clearances (CI
      and CII) were obtained by injecting a second tracer (i.e. [131I]Ap) 15 min after
      the first injection (i.e. [125I]Ap), which by then had a low plasma
      concentration. The kidneys were removed at 30 min, frozen and dissected. During
      control conditions CII/CI averaged 1.06 in OC and IC, and the coefficient of
      variation (CV) between CII/CI ratios of individual tissue samples was 2% in both
      zones. Lowering left renal arterial pressure before the second injection reduced
      GFR proportionally in both zones (34 and 37%) with a CV of intersample CII/CI
      ratios of 5%. We conclude that the method allows precise and repeatable
      measurements of local and zonal GFR.

PMID- 7528962
TI  - [Dose intensified carboplatin monotherapy in advanced ovarian cancer].
AB  - Platinum derivatives are known as the most effective cytostatic agents in ovarian
      carcinoma. The steep dose-response curves described by Hryniuk and Levin [5] make
      them the ideal substances for dose escalation. We treated patients with advanced
      ovarian carcinoma with dose intensified carboplatinmonotherapy six times at AUC 5
      (= +/- 400 mg/m2 in patients with normal renal function). Dose intensification
      was not done by increasing single doses, but by shortening the intervals between
      therapies (23, 21, 17, 14 days). In order to prevent leucopenia G-CSF was
      administered at a dose of 5 micrograms/kg s.c. Besides mild emesis no
      extramedullary toxicity especially no alopezia was documented. Up to an interval
      of 17 days therapy was safe; no thrombocytopenia < 49,000 x 10(6)/L and no
      leucopenia < 1000 x 10(6) was observed. With the intention to arrive at a 14-day
      interval and to attain further dose escalation we will treat future patients with
      a slightly reduced dose of carboplatin (AUC 4) in combination with escalating
      doses of cis-platinum, which is known for its low myelotoxicity.

PMID- 7528969
TI  - Glycoprotein gI of pseudorabies virus: epitope-specific antibody response in mice
      and pigs.

PMID- 7528970
TI  - Head circumference of children with Williams-Beuren syndrome.
AB  - Head circumference is considered an important parameter of brain growth and
      development. Syndrome-specific standards for head circumference in Williams
      Beuren syndrome (WBS) are not available to date, although mental retardation is a
      leading manifestation in the syndrome. Therefore, we investigated head growth in
      63 girls (251 measurements) and 88 boys (298 measurements) with WBS between birth
      and adulthood. Most measurements in both sexes were from the first 4 years of
      life (n = 162 in girls and n = 189 in boys). Mean (+/- SD) head circumference at
      birth was 33.39 +/- 1.38 cm and 34.02 +/- 1.44 cm for term girls and boys,
      respectively. Although head growth in WBS girls and boys was at a slower
      velocity, the pattern of head circumference was similar to that in the normal
      population. After the age of 3 months, head circumference started to fall below
      the normal mean in girls (0.5-2 cm). In boys, mean head circumference was below
      the normal mean already at 1 month of age (2 cm). The deficit increased to 3 cm
      from 6 months to 4 years. Adult OFC was 52.85 +/- 1.75 cm (n = 16) compared to
      55.70 +/- 1.83 cm (n = 46; P < 0.00001) in WBS women and 55.51 +/- 1.68 cm (n =
      30) compared to 57.87 +/- 1.29 cm (n = 31; P < 0.00001) in WBS men. During
      development, microcephaly is only seen in about one third of WBS patients.

PMID- 7528965
TI  - A case of Pick's disease with unusual neuronal inclusions.
AB  - An autopsy case of unusual Pick's disease in a 61-year-old male is described.
      Findings included severe atrophy of the frontal and temporal lobes, pyramidal
      tracts and basal ganglia accompanied by numerous intraneuronal argyrophilic
      hyaline inclusions. His neurological symptoms were constantly progressive during
      the 12-year course, characterized by akinesia and emotional incontinence. The
      inclusions were round, well-demarcated, slightly eosinophilic and intensely
      argyrophilic bodies in the perikarya, and distributed mainly in the subiculum and
      Sommer's sector of the hippocampus, amygdala and affected gyri.
      Immunocytochemically, they contain antigenic determinants of both phosphorylated
      and nonphosphorylated neurofilaments, but were negative for ubiquitin.
      Ultrastructurally, they were composed primarily of skeins of neurofilaments
      intermingled with cell organelles. Tubular profiles studded with granular
      substances, previously reported as a feature of the generalized variant of Pick's
      disease, and Hirano body-like lattice structures were occasionally observed in
      the inclusions. This case represents a slowly progressive neurodegenerative
      disorder characterized by fronto-temporal lobar atrophy and might by categorized
      as a variant of Pick's disease. However, some unusual properties of neuronal
      inclusions may suggest a different pathogenesis from that in classical Pick's
      disease.

PMID- 7528968
TI  - Antibodies to ring-infected erythrocyte surface antigen (Pf155/RESA) protect
      against P. falciparum parasitemia in highly exposed multigravidas women in
      Malawi.
AB  - To determine whether antibodies to defined B-cell epitopes of Plasmodium
      falciparum antigens were related to protection against parasitemic attacks in
      highly exposed pregnant women, two samples of 235 with no initial P. falciparum
      parasitemia (NP) and 89 multigravidas who presented initial P. falciparum
      parasitemia (IP) were enrolled in an antimalarial prophylaxis trial in the
      Mangochi District in Malawi. Sera were collected under effective prophylaxis and
      tested for antibody measurement using FAST-ELISA. Mean antibody titers to
      synthetic peptides reproducing the 3 major B-cell epitopes of the ring-infected
      erythrocyte surface antigen (Pf155/RESA), as (EENV)4, (EENVEHDA)4 and
      (DDEHVEEPTVA)3, were higher in the NP than in the IP multigravidas, and this
      remained consistent within the season of malaria transmission (all p < 0.05). All
      antibodies to Pf155/RESA were positively intercorrelated within each group. Mean
      antibody titers to peptide (PNAN)5 reproducing the major B-cell epitope of the
      circumsporozoite protein (CS protein) were similar between NP and IP
      multigravidas in both dry and rainy season. Antibodies to Pf155/RESA epitopes may
      contribute to immune protection against blood-stage parasite multiplication in
      these highly malaria-exposed pregnant women.

PMID- 7528967
TI  - Glomerular filtration and tubular absorption of the basic polypeptide aprotinin.
AB  - The basic polypeptide aprotinin (Ap), mol. wt 6500, pI 10.5, is filtered in the
      glomeruli, virtually completely taken up by the proximal tubular cells and
      retained there for many hours. This process was studied in rats by determining
      the renal plasma clearance (CAp) as the amount of [125I]Ap accumulated in the
      kidney plus that excreted in the urine per unit of time divided by the integrated
      plasma concentration. In periods lasting 4-20 min after i.v. bolus injection or
      infusion to constant plasma concentration, CAp was 65% of glomerular filtration
      rate (GFR) estimated as kidney plus urinary clearance of [51Cr]EDTA (Ccr-EDTA).
      Less than 0.8% of the filtered Ap appeared in the urine. CAp varied inversely
      with plasma protein concentration in mg ml-1: CAp/Ccr-EDTA = 0.98-0.0058 x Ppr,
      corresponding to a glomerular Gibbs-Donnan distribution for a net molecular
      charge of +6, in agreement with the amino acid composition of Ap. CAp (kidney +
      urinary) was not altered by inhibiting tubular uptake of [125I]Ap by maleate or
      by exceeding the uptake capacity with large doses of unlabelled Ap. Neutralized
      Ap (malonylated) did not accumulate in the kidney, but showed a urinary clearance
      indistinguishable from that of [51Cr]EDTA. Both CAp and Ccr-EDTA were reduced to
      0.04 ml min-1 when glomerular filtration pressure was lowered by ureteral stasis
      and increased Ppr (80-90 mg ml-1). These findings indicate: (1) no steric or
      charge restriction to filtration of Ap in the glomerular membrane, (2) the Gibbs
      Donnan equilibrium should be considered when estimating glomerular sieving of
      charged polypeptides in intact animals (3) charge dependent tubular uptake, (4)
      little or no transtubular transport of intact Ap, (5) no appreciable tubular
      uptake of Ap from the peritubular side and (6) local renal accumulation of Ap in
      a period of up to 20 min may be used to estimate local glomerular filtration
      and/or local proximal tubular reabsorption rates. Model analysis based on the
      appearance of 125I in plasma, the time course of renal Ap content, and literature
      data on subcellular Ap distribution are consistent with two populations of
      endosomes, transporting Ap at widely different rates from the proximal tubular
      brush border to the lysosomes where breakdown occurs at a high rate.

PMID- 7528972
TI  - 10p duplication characterized by fluorescence in situ hybridization.
AB  - We describe a patient with severe failure to thrive, mild-moderate developmental
      delay, cleft lip and palate, and other anomalies. Routine cytogenetic analysis
      documented a de novo chromosome rearrangement involving chromosome 4, but the
      origin of the derived material was unknown. Using chromosome specific painting
      probes, the karyotype was defined as 46,XY,der(4) t(4;10)(q35;p11.23).
      Characterization of the dup(10p) by fluorescence in situ hybridization (FISH)
      analysis provides another example of the usefulness of this technology in
      identifying small deletions, duplications, or supernumerary marker chromosomes.

PMID- 7528971
TI  - Linguistic abilities in children with Williams-Beuren syndrome.
AB  - In recent studies children with Williams-Beuren syndrome (WBS) have been
      characterized as having a distinct neuropsychological profile with verbal
      abilities being superior to visuo-spatial and motor skills. An unusual command of
      language, including excessive use of verbal stereotypes, social phrases, and
      cliches has been noticed. The aim of this study is to establish whether the
      quality and quantity of verbal behavior, and the articulation and tonal quality
      of the voices of children with WBS differ from other children with nonspecific
      developmental disabilities. A group of 25 children with WBS and a control group
      of 25 children matched for age (4-10 years), sex (12 girls; 13 boys), and non
      verbal reasoning abilities (mean IQ = 79) were investigated. The Heidelberg
      Language Development Test and a picture story were administered. The mothers were
      asked to answer a questionnaire to assess the articulation and the vocal
      characteristics of their children. The results show that children with WB
      syndrome do not differ in most qualitative and quantitative tasks with regard to
      verbal competence. They produce significantly more correct plural-singular
      formations than the control children (t = 2.49, P < 0.01) on a primitive level of
      grammatical competence. In general, their articulation was reported to be more
      exact and clear (t = -2.73, P < 0.006). More mothers of children with WBS noticed
      a production of stereotypes, the use of social phrases, and cliches than did
      mothers of the control children (Chi square = -6.67 P < 0.005). Children with WBS
      were less likely to lisp as compared to the control children (Chi square = 2.08,
      P = 0.074).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528973
TI  - Male-to-male transmission of mild Brachmann-de Lange syndrome.
AB  - We report on a father and son with mild Brachmann-de Lange syndrome. Previous
      reports have documented apparent autosomal dominant transmission; however, only
      one example of male-to-male transmission of possible Brachmann-de Lange syndrome
      has been reported. This case provides further evidence of the existence of an
      autosomal dominant form of Brachmann-de Lange syndrome.

PMID- 7528975
TI  - Ionic currents during action potentials in mammalian skeletal muscle fibers
      analyzed with loose patch clamp.
AB  - The loose patch-clamp technique was applied to analyze transmembrane currents
      during propagating action potentials in superficial fibers of musculi extensor
      digitorum longus of the mouse in vitro. Experimentally three components were
      identified in the transmembrane current: 1) a capacitive, 2) an inward sodium,
      and 3) an outward potassium current. Other components were negligible. The
      capacitive current was similar in shape to the first derivative of the
      intracellularly measured action potential. Tetrodotoxin, tetraethylammonium, and
      4-aminopyridine, applied in the pipette, were used to identify the contribution
      in the current by sodium and potassium ions. With extracellularly applied
      depolarization steps only a sodium current was observed, not a potassium current.
      Occasionally found outward currents were artifactual. The behaviour of delayed
      rectifier potassium channels in muscle fiber membranes is discussed in the light
      of these unexpected findings. We conclude that potassium channel activity
      contributing to and measured during action potential generation is in some way
      inaccessible to loose patch extracellular voltage-clamp stimulation and that
      loose patch action current recording is a useful noninvasive method to analyze
      membrane conductances involved in action potential generation.

PMID- 7528974
TI  - Genetics of the Costello syndrome.
AB  - Although Costello syndrome is considered to be an autosomal recessive disorder,
      review of 20 families demonstrated that the 37 sibs of the probands were all
      normal. In 6 families on whom pedigrees were not available, 2 affected sib-pairs
      were born. Even if there were no normal offspring in these latter families, the
      occurrence of the Costello syndrome in only 2 of 39 sibs virtually excludes an
      autosomal recessive inheritance pattern (P = 0.999). Moreover, a significant
      increase of mean paternal age (38.0 yr) and paternal-maternal age difference
      (7.36 yr) suggests sporadic autosomal dominant mutations as a likely cause. The 2
      reported cases of affected sibs born to healthy parents may be explained by
      gonadal mosaicism, although heterogeneity with a small proportion of recessively
      inherited cases cannot be excluded.

PMID- 7528978
TI  - Cellular mechanisms and physiological implications of quantal Ca2+ release in
      pancreatic acinar cells.
AB  - Previous studies in pancreatic acini demonstrated that submaximal concentrations
      of agonist release only a portion of Ca2+ from the intracellular pool during the
      first few seconds of stimulation. Despite continued stimulation, no further
      release of pool Ca2+ takes place. This process has been termed quantal release.
      Previous hypotheses have proposed that quantal release results from varying
      sensitivities of the intracellular pool to inositol 1,4,5-trisphosphate (IP3)
      mediated Ca2+ release. The purpose of the present experiments was to further
      characterize the cellular mechanism of quantal release and to determine the role
      of quantal release in pancreatic enzyme secretion. The results indicate that the
      phenomenon of quantal calcium release is not due to varying sensitivities of the
      intracellular Ca2+ stores to IP3. Quantal release results from both an intrinsic
      property of the IP3 receptor, which causes it to transport Ca2+ transiently, and
      from the transient nature of the increase in IP3 generated by submaximal agonist
      concentration. With this mechanism, sequential additions of physiological
      concentrations of agonist cause transient increases in intracellular Ca2+
      concentration leading to bursts of enzyme secretion.

PMID- 7528977
TI  - Pancreatic endocrine responses to substance P and calcitonin gene-related peptide
      in conscious calves.
AB  - Both substance P (SP) and calcitonin gene-related peptide (CGRP; 0.13
      micrograms.min-1.kg-1 for 10 min) produced a significant rise in arterial plasma
      pancreatic polypeptide (PP) concentration, and additive responses were obtained
      when both peptides were infused simultaneously and/or with acetylcholine (0.7
      micrograms.min-1.kg-1 ia). The PP response to SP was abolished by intravenous
      infusions of glucose, whereas those to CGRP and acetylcholine were not
      significantly affected. Neither SP nor CGRP had any effect on plasma insulin
      concentration, either in the presence or absence of exogenous glucose, whether
      infused singly or together, or in the presence of acetylcholine. SP, but not
      CGRP, produced a small but statistically significant rise in mean plasma glucagon
      concentration when infused together with acetylcholine. These results suggest
      that SP and CGRP may modulate the secretion of PP and glucagon in the normal
      conscious calf but not that of insulin. It is also possible that SP modulates
      secretion of pancreatic glucagon in these animals.

PMID- 7528976
TI  - Heterotetramer formation and charybdotoxin sensitivity of two K+ channels cloned
      from smooth muscle.
AB  - Delayed rectifier K+ channels are involved in the electrical activity of all
      excitable cells. The relationship between native K+ currents recorded from these
      cells and cloned K+ channel cDNAs has been difficult to ascertain partly because
      of contradictions in pharmacological characteristics between native and expressed
      currents. Through the study of the charybdotoxin (CTX) pharmacology of two cloned
      smooth muscle delayed rectifier K+ channels (cKv 1.2 and cKv1.5) expressed in
      oocytes, evidence for heterotetramer formation was obtained. We have shown that
      the presence of even a single CTX-insensitive subunit renders the
      heterotetrameric channel insensitive to CTX. The two K+ channel clones differ in
      an amino acid at the mouth of the pore region, which may be in a position to
      block the access of CTX to its binding site and hence determine CTX sensitivity
      of the heterotetrameric channel. These results may explain discrepancies reported
      between native and cloned smooth muscle K+ channels.

PMID- 7528979
TI  - Protective role of NO in hepatic microcirculatory dysfunction during endotoxemia.
AB  - Nitric oxide (NO) has been reported to have a protective function in attenuating
      hepatic injury during endotoxemia or sepsis. As a result, the role of NO in
      attenuating the hepatic microcirculatory alterations associated with endotoxemia
      was investigated in mice by in vivo microscopy. The livers were examined 2 h
      after intravenous injection of Escherichia coli 0111:B4 lipopolysaccharide (LPS)
      alone or in combination with inhibitors of the synthesis of NO, NG-nitro-L
      arginine methyl ester or NG-monomethyl-L-arginine. In the animals treated with
      the combination of NO synthase inhibitors and LPS, leukocyte adherence was
      increased threefold above that in animals treated with LPS alone. This was
      accompanied by a 33% reduction in sinusoidal blood flow. Simultaneous
      administration of L-arginine, but not D-arginine, eliminated these
      microcirculatory disturbances. The results demonstrate that inhibition of LPS
      stimulated NO production results in an early hepatic microvascular inflammatory
      response to a dose of endotoxin which by itself is scarcely inflammatory. This
      suggests that NO plays a significant role in stabilizing the hepatic
      microcirculation during endotoxemia, thereby helping to protect the liver from
      ischemia and leukocyte-induced oxidative injury.

PMID- 7528980
TI  - Regulation of riboflavin intestinal uptake by protein kinase A: studies with Caco
      2 cells.
AB  - Although the mechanism of riboflavin (RF) intestinal uptake has been the subject
      of many studies, virtually nothing is known about the cellular regulation of the
      uptake process. In the present study, we investigated the role of protein kinase
      A (PKA)- and C (PKC)-mediated pathways in the regulation of RF intestinal uptake
      using the confluent Caco-2 monolayers. Treatment of Caco-2 cells with 3-isobutyl
      1-methylxanthine (IBMX), forskolin, cholera toxin, or dibutyryl adenosine 3',5'
      cyclic monophosphate caused a significant inhibition in RF uptake. The inhibitory
      effect of IBMX was reversible and resulted from a significant decrease in the
      maximal velocity of the RF uptake process with no change in its apparent
      Michaelis constant. The IBMX-induced inhibition in RF uptake was not mediated via
      inhibition in the synthesis of the RF carrier protein or through inhibition in
      the recruitment of preexisting carrier protein into the plasma membrane.
      Calyculin A also inhibited RF uptake when added alone and further potentiated the
      inhibitory effect of IBMX when added together. Phorbol 12-myristate 13-acetate or
      chelerythrine, on the other hand, showed no significant effect on RF uptake.
      These results demonstrate for the first time that compounds that increase
      intracellular cAMP levels downregulate RF intestinal uptake and that this effect
      is mediated via a decrease in the activity of the RF uptake carrier. It is
      suggested that a PKA-mediated pathway(s) plays an important role in regulating RF
      intestinal uptake.

PMID- 7528981
TI  - Distribution of NOS in normoxic vs. hypoxic rat lung: upregulation of NOS by
      chronic hypoxia.
AB  - Expression and localization of nitric oxide synthase (NOS) in the lungs of
      chronically hypoxic and normoxic rats were studied using both
      immunohistochemistry and NADPH diaphorase (NADPH-d) staining techniques. In the
      normoxic and in the hypoxic rat, NOS was detected by both methods in the
      endothelium of large pulmonary vessels and in the epithelium of bronchi and
      bronchioli. NOS expression was not detected in the endothelium of normoxic
      pulmonary resistance vessels but was prominently expressed in the endothelium of
      these vessels after 2-4 wk of chronic hypoxia. In contrast to small pulmonary
      vessels, the endothelium of small bronchial vessels exhibited NOS immunostaining
      in both normoxic and hypoxic lungs. Hypoxia was also found to induce de novo NOS
      expression in the smooth muscle of large and small pulmonary vessels and in
      bronchial smooth muscle. NOS enzyme activity in lung homogenates was assessed by
      [3H]arginine to [3H]citrulline conversion. The activity of soluble NOS, but not
      particulate NOS, was increased in the hypoxic lungs. These results demonstrate
      chronic hypoxia-induced upregulation of NOS protein expression and activity in
      the rat lung, suggesting a potentially important role of nitric oxide in
      adaptation of the pulmonary circulation to chronic hypoxia. The lack of
      immunostaining in small pulmonary resistance vessels is also consistent with
      physiological studies suggesting that NO may not be involved in the mechanism for
      maintaining the normally low pulmonary vascular resistance.

PMID- 7528984
TI  - Expression of substance P and its precursor forms in vagal, tracheal, and lung
      tissues of the guinea pig.
AB  - Steady-state levels of the prototypic tachykinin neuropeptide substance P (SP)
      and its major precursor form substance P-glycine (SP-G) were detected and
      authenticated in guinea pig vagal and respiratory tissues by radioimmunoassay
      (RIA), combined high-performance liquid chromatography (HPLC)/RIA analyses, and
      immunohistochemistry. Four antisera were employed: anti-SP that recognizes the
      amidated COOH-terminal of SP and is specific for the mature peptide, anti-SP4-10
      that recognizes the midportion 4-10 amino acid sequence of SP and is highly
      specific for both mature SP and extended precursor forms of SP, anti-SP-G that is
      highly specific for the unamidated COOH-terminal of SP-G, and affinity-purified
      anti-SP-G-K that is capable of detecting SP-G and minor forms of SP precursor in
      immunohistochemical analyses. In all examined areas, the content of substance P4
      10-like immunoreactivity (SP4-10-LI) quantified by RIA with the use of anti-SP4
      10 was greater than that quantified by RIA with the use of anti-SP serum, thereby
      providing biochemical evidence of steady-state expression of extended precursor
      forms of SP. Immunohistochemical analyses demonstrated labeled axonal profiles
      indicating the presence of immunoreactive SP as well as immunoreactive forms of
      SP precursor within lung hilum and in small fibers in the parenchyma, with no
      evidence of labeled neuronal cell bodies in these same areas.

PMID- 7528985
TI  - Dissociation between antiproteinuric and antihypertensive effect of angiotensin
      converting enzyme inhibitors in rats.
AB  - To clarify whether angiotensin converting enzyme (ACE) inhibitors prevent
      progressive renal injury directly by their antihypertensive effect we
      administered the ACE inhibitor lisinopril to male MWF/Ztm rats as a single daily
      dose that lowered blood pressure for only 9 of 24 h. We investigated the effects
      of this treatment in short- and long-term studies and compared them with another
      antihypertensive drug, the calcium channel blocker nitrendipine, given to
      partially control blood pressure as done with the ACE inhibitor. In untreated
      animals systemic hypertension, proteinuria, and glomerulosclerosis developed
      spontaneously with age, and lisinopril reduced systemic hypertension and
      prevented proteinuria and glomerular lesions. Nitrendipine, despite similar blood
      pressure control, was ineffective in preventing both proteinuria and
      glomerulosclerosis. After 2 mo of treatment glomerular capillary pressure was
      significantly reduced by lisinopril and slightly but significantly increased by
      nitrendipine, compared with untreated controls. The ultrafiltration coefficient
      was significantly higher in lisinopril than in controls and not significantly
      changed by nitrendipine. With both drugs, however, glomerular hemodynamic effects
      were observed only at a few hours after administration and were abolished before
      the next administration. No significant changes in glomerular tuft volume were
      observed in treated and untreated animals after 2 and 6 mo of observation. Thus
      ACE inhibitor, despite only partial control of systemic blood pressure,
      effectively prevented proteinuria and glomerular injury. Comparable blood
      pressure control obtained with a calcium channel blocker was not associated with
      renal protection. These results suggest that ACE inhibitors could protect
      glomerular microcirculation by a mechanism that is not directly related to their
      antihypertensive action.

PMID- 7528983
TI  - Insulin-like growth factor axis in airway smooth muscle cells.
AB  - Insulin-like growth factors (IGFs) mediate cell proliferation and differentiation
      and bind with high affinities and specificities to IGF receptors and IGF-binding
      proteins (IGFBPs). We examined the roles of these three groups of proteins in
      cultured rabbit airway smooth muscle (ASM) cells. Affinity cross-linking of IGF-I
      and IGF-II to membranes of ASM cells revealed type 1 and type 2 IGF receptors.
      Western ligand blot analysis of ASM cell-conditioned medium revealed the presence
      of a single IGFBP band that precipitated with an antibody specific to IGFBP-2.
      ASM cells secreted radioimmunoassayable IGF-II; however, no IGF-I was detected
      under the same conditions. Two molecular weight forms of IGF-II were produced by
      the ASM cells. Exposure of cells to 1,000 ng/ml of IGF-I stimulated them to
      proliferate to 230 +/- 9.7% of their respective controls. Exposure to 1,000 ng/ml
      of IGF-II was approximately 40% as effective as exposure to 1,000 ng/ml of IGF-I.
      Both IGF-I and IGF-II exhibited binding to the type 1 IGF receptor. In summary,
      IGFs are mitogens for cultured rabbit ASM cells, and their actions are most
      likely mediated through the type 1 IGF receptor. The ASM cells secrete IGF-II and
      IGFBP-2, and the latter could modulate the actions of the IGFs in these cells.

PMID- 7528982
TI  - Immunohistochemical demonstration of a paracrine role of nitric oxide in
      bronchial function.
AB  - We addressed the controversial role of nitric oxide (NO) in bronchial function by
      an immunohistochemical study of the localization of NO synthase (NOS) and its
      effector protein, soluble guanylate cyclase, in rat bronchus. For this study, a
      monoclonal antibody to the bovine constitutive neuronal NOS was developed and
      characterized. In Western blot analysis, this monoclonal antibody (anti-NOS
      antibody) reacted with bovine cerebellum NOS (150 kDa) as well as with
      structurally different NOSs from cultured bovine aortic endothelial cells (130
      kDa) and cultured RAW 264.7 macrophages (130 kDa). The reactivity of anti-NOS
      antibody was confirmed by immunohistochemical staining of rat cerebellum,
      arterial endothelial cells, and cultured stimulated macrophages. When the
      distribution of NOS in rat airway was characterized, the anti-NOS antibody showed
      immunoreactivity within respiratory epithelium but not in the bronchial smooth
      muscle. The NADPH-diaphorase staining correlated with the immunostaining. In
      contrast, a monoclonal antibody to the rat lung-soluble guanylate cyclase
      immunostained respiratory smooth muscle but not epithelium. This study suggests a
      paracrine role for NO in bronchial function analogous to the function of the NOS
      soluble guanylate cyclase pathway in blood vessels.

PMID- 7528987
TI  - Chronic, intermittent loading alters mechanosensitive channel characteristics in
      osteoblast-like cells.
AB  - The effects of chronic, intermittent strain on the mechanosensitive cation (SA
      cat) channels in UMR-106.01 osteoblast-like osteosarcoma cells were studied using
      patch-clamp techniques. Chronically strained cells demonstrated significantly
      larger increases in whole cell conductance when subjected to additional
      mechanical strain than nonstrained controls (69.0 +/- 15.1 vs. 14.1 +/- 3.1%; P <
      0.001). This increase could be blocked by the SA-cat channel inhibitor,
      gadolinium, and corresponded to a three- to fivefold increase in SA-cat channel
      activity. Chronic strain increased the number of open channels in response to
      stretch and induced spontaneous SA-cat channel activity in 33% of the patches of
      strained cells. Graded increases in negative patch pressure demonstrated that SA
      cat channels in chronically strained cells were activated at significantly lower
      levels of mechanical perturbation than nonstrained controls. These data suggest
      that chronic, cyclic strain reduces the activation threshold of the SA-cat
      channel and further strengthen our hypothesis that this channel may act as a
      mechanotransducer for the activation of bone remodeling by physical strain.

PMID- 7528986
TI  - Murine polycystic kidney epithelial cell lines have increased integrin-mediated
      adhesion to collagen.
AB  - Polycystic kidney disease (PKD), in which epithelial cysts arise from or instead
      of normal renal tubules, is one of the most common genetic diseases. It has both
      autosomal dominant and autosomal recessive inheritance in humans and in
      experimental animals. Epithelial cells lining the cysts have an increased rate of
      proliferation, abnormal polarity of Na-K-adenosinetriphosphatase, which is
      localized to apical and sometimes lateral membrane domains, and an abnormal
      extracellular matrix. One hypothesis that explains the simultaneous acquisition
      of these characteristics as the result of several different genetic mutations is
      that cell-matrix interactions, which are known to regulate cell proliferation and
      cell polarity, are altered in PKD. I have created immortalized renal epithelial
      cell lines from C57Bl/6Jcpk mice with PKD, an autosomal recessive trait in these
      animals, and from their phenotypically normal littermates. Using these cell
      lines, I show that polycystic cells have increased adhesion to collagens and
      laminin mediated by an integrin. These results demonstrate that cell-matrix
      interactions are defective in PKD and suggest that these interactions may be
      involved in the abnormalities of cell polarity and cell proliferation seen in
      these disorders.

PMID- 7528988
TI  - Sialyl Lewisx-containing oligosaccharide exerts beneficial effects in murine
      traumatic shock.
AB  - We investigated the effects of a soluble sialyl Lewisx-containing oligosaccharide
      (SLex-OS) in a rat model of traumatic shock. Pentobarbital-anesthetized rats
      subjected to Noble-Collip drum trauma developed a shock state characterized by
      marked hypotension, a survival time of 85 +/- 15 min, significant increases in
      ileal myeloperoxidase (P < 0.01), and plasma free amino-nitrogen activities (P <
      0.01). Treatment with SLex-OS (10 mg/kg) 10 min posttrauma prolonged survival
      time to 198 +/- 29 min (P < 0.01), significantly attenuated ileal myeloperoxidase
      activity (P < 0.01), and diminished the accumulation of plasma free amino
      nitrogen (P < 0.01), drug vs. vehicle, respectively. Furthermore, endothelium
      dependent relaxation to acetylcholine in superior mesenteric artery rings
      isolated from SLex-OS-treated shock rats was significantly preserved (70 +/- 6
      vs. 40 +/- 5% relaxation). No beneficial effects were observed using a
      nonfucosylated control oligosaccharide. Moreover, addition of SLex-OS
      significantly inhibited unstimulated human polymorphonuclear neutrophil (PMN)
      adherence in vitro to trauma-activated superior mesenteric artery endothelium ex
      vivo (P < 0.001). Our results indicate that SLex-OS exerts beneficial effects in
      traumatic shock states by blocking selectin-mediated leukocyte-endothelium
      interaction, thus improving survival, attenuating intestinal PMN accumulation,
      and diminishing shock-induced tissue injury.

PMID- 7528990
TI  - Increases in local cerebral blood flow associated with somatosensory activation
      are not mediated by NO.
AB  - Effects of inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl
      ester (L-NAME) on the increases in local cerebral blood flow (LCBF) produced in
      the whisker-to-barrel sensory pathway by vibrissal stimulation were studied in
      conscious rats with the autoradiographic iodo[14C]antipyrine method. Unilateral
      whisker stroking increased LCBF in the ipsilateral trigeminal spinal and
      principal sensory nuclei, contralateral ventral posteromedial thalamic nucleus,
      and contralateral somatosensory barrel cortex. Intravenous L-NAME (30 mg/kg)
      lowered baseline LCBF without altering the percent increases due to stimulation.
      Intracisternal infusions of L-NAME in doses about 10 times the molar content of
      free arginine in brain inhibited brain NO synthesis activity by 88%, but the
      percent augmentations of LCBF by stimulation remained unchanged. Chronic
      treatment with L-NAME (50 mg/kg ip twice daily for 4 days) inhibited NO synthase
      activity in brain by 84% but also failed to reduce the percent increases in LCBF
      due to stimulation. These results indicate that NO does not mediate the increases
      in LCBF associated with functional activation.

PMID- 7528991
TI  - Capillary perfusion during ischemia-reperfusion in subcutaneous connective tissue
      and skin muscle.
AB  - Ischemia-reperfusion injury was investigated in terms of functional capillary
      density (FCD), capillary red blood cell velocity (cRBCv), and arteriolar and
      venular diameter after 4-h ischemia in the unanesthetized hamster skin-fold
      preparation. Animals in group 1 were studied by transillumination. Group 2
      received a bolus injection of fluorescein isothiocyanate (FITC)-dextran (mol wt
      150,000) and was studied by transillumination (zone 1) and epi-illumination (zone
      2). In group 1, FCD decreased after ischemia (92% of baseline, 30 min), returning
      to control up to 24 h. cRBCv increased after reperfusion, being 175% of baseline
      at 24 h. Arterioles and venules dilated for 24 h after reperfusion. In group
      2/zone 2, FCD progressively decreased to 11% of control, arteriolar dilation was
      inhibited, and cRBCv increased 30 min and 2 h after reperfusion. Tissue perfusion
      index (FCD x cRBCv) increased 158% in group 1 at 24 h, did not change in group
      2/zone 1, and was 9% of control at 24 h in group 2/zone 2 (P < or = 0.05). We
      conclude that increased perfusion is a normal reaction to ischemia-reperfusion
      injury in this model, and previously observed capillary no reflow is due to FITC
      dextran phototoxicity.

PMID- 7528992
TI  - Attenuation of sodium nitroprusside responses after prolonged incubation of rat
      aorta with endotoxin.
AB  - We investigated the effects of prolonged treatment with Escherichia coli
      lipopolysaccharide (LPS) on the responses to sodium nitroprusside (SNP) in
      endothelium-denuded rat aortic strips. Incubation of the aortic strips with LPS
      for 24 h dramatically attenuated relaxation and guanosine 3',5'-cyclic
      monophosphate (cGMP) formation by SNP, which were significantly restored by the
      inhibition of nitric oxide (NO) production with N omega-nitro-L-arginine. In the
      aorta coincubated with LPS and protein synthesis inhibitor (dexamethasone or
      cycloheximide, which prevents induction of endotoxin-inducible NO synthase), no
      attenuation of the relaxation was observed and the cGMP formation was
      significantly restored. Relaxation response to 8-bromo-cGMP or papaverine was not
      attenuated, even after 24 h of incubation. These results suggest that the
      attenuation of SNP responses is mainly associated with a decrease in the
      activation of guanylate cyclase (GC) as a consequence of the prolonged exposure
      to muscle-derived NO. Moreover SNP in the presence of methylene blue evoked a
      small but apparent relaxation of 24-h-incubated aorta without significant
      elevation of cGMP, suggesting the involvement of cGMP-independent pathways in the
      remaining relaxation produced by SNP.

PMID- 7528989
TI  - Proportional arteriolar growth accompanies cardiac hypertrophy induced by volume
      overload.
AB  - Volume overload-induced cardiac hypertrophy is characterized by normal coronary
      reserve and maximal flow. Accordingly, we tested the hypothesis that both
      arteriolar and capillary growth are proportional to the magnitude of hypertrophy
      in this model. Five months after performing an aortocaval fistula [arteriovenous
      (A-V) shunt] in young rats, right and left ventricles were 61 and 55%,
      respectively, heavier than their sham controls. Using morphometric methods and
      image analysis, we found that increases in cardiac myocyte cross-sectional area
      accounted for approximately 50% of the hypertrophy and that arteriolar length
      density (LV) (7.5 +/- 0.9 and 7.0 +/- 0.4 mm/mm3) and the frequency distribution
      of arteriolar diameters were similar in the hearts from A-V shunt and control
      rats. Capillary LV in the right ventricle was similar in the two groups; in the
      left ventricle a significantly lower LV for the A-V shunt rats was noted only in
      the endomyocardium. Capillary volume density was not attenuated in the A-V shunt
      rats, since slightly larger luminal diameters compensated for any decrements in
      LV in the left ventricle. These findings provide an anatomic basis for the
      observation that maximal myocardial perfusion is not necessarily compromised in
      ventricular enlargement due to aortocaval fistula. Because diastolic volume is
      increased in this model and thereby provides a stretch on the microvasculature,
      our findings are consistent with those from other models of cardiac hypertrophy
      in which enhancement of mechanical factors is associated with angiogenesis.

PMID- 7528993
TI  - Regulation of inducible nitric oxide synthase gene by interleukin-1 beta in rat
      vascular endothelial cells.
AB  - To elucidate the regulation of endothelial inducible nitric oxide synthase
      (iNOS), we studied the effects of interleukin (IL)-1 beta on production of nitric
      oxide (NO) and expression of iNOS mRNA and iNOS protein in cultured rat aortic
      endothelial cells (ECs) by measurement of NO2-/NO3- (NOx) and Northern blot and
      Western blot analyses. Among several cytokines and bacterial lipopolysaccharide
      tested, IL-1 beta most effectively stimulated NOx production. IL-1 beta dose and
      time dependently stimulated NOx production. Northern blot analysis using cDNA for
      mouse liver iNOS as a probe showed that IL-1 beta induced expression of iNOS mRNA
      and stimulated NOx production in a dose- and time-dependent manner. Transforming
      growth factor (TGF)-beta and dexamethasone blocked the IL-1 beta-induced NOx
      production as well as expression of iNOS mRNA and protein. TGF-beta dose
      dependently inhibited the IL-1 beta-induced NOx production and iNOS mRNA
      expression. Northern blot analysis for the decay of the IL-1 beta-induced iNOS
      mRNA revealed the approximate half-life of 4 h. These data indicate that IL-1
      beta induces iNOS gene expression and de novo synthesis of iNOS and subsequent NO
      generation in vascular endothelium and that TGF-beta and glucocorticoid block
      iNOS gene expression at the transcriptional level.

PMID- 7528994
TI  - Rat and rabbit heart infarction: effects of anesthesia, perfusate, risk zone, and
      method of infarct sizing.
AB  - Rabbits and rats are becoming popular models for in vitro as well as in situ
      studies of myocardial infarction. In the present analysis we evaluated the
      results of several of our completed investigations and tested whether blood-free
      perfusate, anesthesia, or risk zone size affects infarction in these species. In
      addition, the influence of the method used for determining infarct size
      (histology or histochemistry) was examined in rabbits. All hearts experienced 30
      min of regional ischemia followed by either 2-3 h of reperfusion in animals in
      which infarct size was assessed by staining with triphenyltetrazolium chloride or
      72 h in those in which histological methods were used to measure infarct size.
      Eighteen rabbit and seven rat hearts perfused with Krebs buffer, seventeen open
      chest rabbits, eight rats anesthetized with pentobarbital, and ten conscious
      rabbits were studied. Risk zone size measured with fluorescent particles was
      plotted against infarct size. Infarct size was linearly correlated with risk zone
      size and did not differ among models for each species. In rat hearts the
      regression line passed through the origin so that zero infarction occurred with
      zero risk zone size. However, in the rabbit heart there was no apparent
      infarction for risk zone sizes < 0.3 cm3. Although the relationship between risk
      zone and infarction was found to be remarkably independent of the model chosen,
      the nonzero intercept for the rabbit heart can be an important, previously
      unrecognized source of experimental variability when infarct size is expressed as
      a percentage of the risk zone.

PMID- 7528995
TI  - A monoclonal antibody to P-selectin ameliorates injury associated with
      hemorrhagic shock in rabbits.
AB  - P-selectin (CD62P) can participate in leukocyte rolling when it is expressed on
      the surface of endothelial cells. We examined the role of CD62P in hemorrhagic
      shock and resuscitation. Rabbits were treated with saline, an anti-CD62P (alpha
      CD62P) monoclonal antibody (MAb; PB1.3), an isotype-matched MAb (PNB1.6), or an
      alpha-CD18 MAb (60.3). Catheters were placed in the femoral artery and vein for
      monitoring, and cardiac output was then reduced to 33% of baseline for 1.5 h.
      Shed blood was returned, and resuscitation was continued to maintain the cardiac
      output to within 90% of baseline. There were no statistical differences between
      the saline- and MAb PNB1.6-treated groups; they were therefore combined into a
      control group. The MAb PB1.3- and MAb 60.3-treated groups required significantly
      less fluid resuscitation than the controls (12, 17, and 56 ml/kg, respectively).
      We conclude that MAbs directed to functional epitopes of either CD62P or CD18
      provide significant protection from vascular injury after hemorrhagic shock.

PMID- 7528997
TI  - Mechanism of the negative inotropic effect of adenosine in guinea pig atrial
      myocytes.
AB  - The ionic basis of the negative inotropic effect of adenosine on guinea pig
      atrial myocytes was studied. Membrane potentials and currents were measured using
      a whole cell patch-clamp technique. The contractility was assessed by video
      quantitation of cell twitch amplitude. Adenosine shortened action potential
      duration [measured at 90% repolarization (APD90)] and decreased twitch amplitude
      in a concentration-dependent manner. The maximal effects of adenosine (100
      microM) were to reduce APD90 from 102 +/- 14 to 34 +/- 8 ms (n = 11) and twitch
      amplitude from 4.3 +/- 0.9 to 1.5 +/- 0.4 microns (n = 8). The concentration of
      adenosine that caused one-half of the maximal reductions of twitch amplitude and
      of APD90 was 0.6 microM. Reductions in APD90 and in twitch amplitude were
      parallel and highly correlated (r = 0.98). Decreases in twitch amplitude by
      adenosine could be mimicked by application of voltage-clamp pulses with durations
      similar to the durations of action potentials in the presence of adenosine. Clamp
      pulse could reverse adenosine-induced but not cadmium chloride-induced decreases
      in twitch amplitude. Adenosine activated the inwardly rectifying K+ current
      (IK,Ado), but did not significantly decrease the L-type Ca2+ current (ICa,L).
      Adenosine reduced the effects of BAY K 8644 on APD90 and twitch amplitude but did
      not attenuate the BAY K-induced increase in ICa,L. The effects of adenosine on
      APD90 and twitch amplitude could be reversed after activation of IK,Ado was
      inhibited by intracellular application of cesium and tetraethylammonium
      chloride.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7528996
TI  - Enhanced pulmonary arterial dilation to arginine vasopressin in chronically
      hypoxic rats.
AB  - Chronic hypoxic exposure elicits pulmonary vascular remodeling and may alter
      normal pulmonary endothelial function. We examined the vasodilatory response to
      the receptor-mediated endothelium-dependent dilator arginine vasopressin (AVP),
      the non-receptor-mediated endothelium-dependent dilator A-23187, and the nitric
      oxide (NO) donor sodium nitroprusside in lungs isolated from control or
      chronically hypoxic rats. Lungs were isolated from male Sprague-Dawley rats and
      perfused with a physiological saline solution containing 4% albumin. Arterial and
      venous pressures were monitored and microvascular pressure was estimated by
      double occlusion, allowing assessment of segmental resistances. After
      equilibration, lungs were constricted with the thromboxane mimetic U-46619. Upon
      development of a stable pressor response, lungs were dilated with one of the
      above agents. A series of doses of AVP was administered to separate groups of
      lungs from control or chronically hypoxic rats. Lungs from chronically hypoxic
      rats exhibited an augmented dilatory response to AVP compared with control lungs,
      and this effect was due to enhanced dilation of precapillary segments. The total
      and segmental vasodilatory responses to A-23187 and sodium nitroprusside were not
      different between the two groups of lungs, suggesting that chronic hypoxia did
      not upregulate the enzyme NO synthase or enhance the vascular smooth muscle
      responsiveness to NO. Thus our data suggest that the augmented total and
      pulmonary arterial dilation to AVP after chronic hypoxia is most likely due to
      altered receptor-mediated processes of the hormone.

PMID- 7528998
TI  - CGRP enhances induction of NO synthase in vascular smooth muscle cells via a cAMP
      dependent mechanism.
AB  - Experiments were designed to examine whether calcitonin gene-related peptide
      (CGRP), a potent adenosine 3',5'-cyclic monophosphate (cAMP)-dependent
      vasodilator, affects the production of NO evoked by interleukin-1 beta) (IL-1
      beta) in cultured rat aortic smooth muscle cells (SMC). CGRP, in a concentration
      dependent manner, enhanced the release of nitrite (a stable oxidation product of
      NO) and the formation of L-citrulline from L-arginine caused by IL-1 beta. Two
      cAMP-dependent vasodilators, forskolin and isoproterenol, and the activator of
      the cAMP-dependent protein kinase, Sp-cAMPS, also enhanced the release of nitrite
      and the formation of L-citrulline evoked by IL-1 beta. The enhancing effect of
      isoproterenol required the presence of the vasodilator during the induction of NO
      synthase (NOS). IL-1 beta-treated vascular SMC inhibited the aggregation of
      indomethacin-treated platelets. Inhibition of platelet aggregation was more
      marked with SMC exposed to a combination of IL-1 beta and either CGRP or
      isoproterenol than with cells exposed to IL-1 beta alone. This inhibition was
      prevented by methylene blue and oxyhemoglobin. IL-1 beta induced the expression
      of inducible NOS mRNA in vascular SMC, which was enhanced by coincubation of IL-1
      beta with either CGRP, isoproterenol, or forskolin. These observations indicate
      that CGRP via a cAMP-dependent mechanism potentiates the IL-1-beta-induced
      production of NO by enhancing the expression of inducible NOS. Therefore CGRP may
      contribute to the substantial production of NO in the vasculature during septic
      shock, which accounts, at least in part, for the collapse of the vascular system.

PMID- 7528999
TI  - Monocyte adhesion to cerebromicrovascular endothelial cells derived from
      hypertensive and normotensive rats.
AB  - The stroke risk factor hypertension may function as a predisposing agent by
      increasing the vulnerability of blood vessels to thrombosis or hemorrhage. The
      research here demonstrates that cerebrovascular endothelial cells (EC) from
      spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) rats exhibit
      similar levels of adhesiveness for syngeneic peripheral blood monocytes (e.g.,
      22.53 +/- 1.32 and 24.35 +/- 1.16%, respectively). Monocyte adhesion to SHR EC
      was dramatically increased by treatment of EC with lipopolysaccharide, interferon
      gamma, or interleukin-1 beta and tumor necrosis factor-alpha (e.g., 106, 68, and
      171%, respectively). Identical treatment of WKY EC also increased adhesion albeit
      at significantly lower levels than observed on concomitantly tested SHR EC (e.g.,
      47.8, 12.7, and 60.7%, respectively). Allogeneic combinations of monocytes and EC
      again demonstrated significantly more upregulation of adhesion by treatment of
      SHR EC than WKY EC. Characterization of these adhesive interactions revealed the
      interplay of adhesion pathways, which include lymphocyte functional antigen
      1/intercellular adhesion molecule-1 (ICAM-1), Mac-1/ICAM-1, and very late
      activation antigen-4/vascular adhesion molecule-1 as well as other undetermined
      mechanisms. In summary, these findings indicate hypertension may enhance
      responsiveness of endothelium to factors that promote monocyte adhesion.

PMID- 7529000
TI  - Chloride and cation currents activated by bradykinin in coronary venular
      endothelial cells.
AB  - Bradykinin (BK) is known to activate several types of ion channels in endothelial
      cells, including a K+ channel and a nonselective cation channel. The predominant
      BK-activated current in most endothelial cells appears to be an outward, Ca(2+)
      activated K+ current. We consistently recorded a rapidly activated, spontaneously
      inactivated inward current stimulated by BK in bovine coronary venular
      endothelial cells (CVECs). With the use of a whole cell, perforated patch
      recording mode, the average magnitude of the current was -293 +/- 38 pA.
      Simultaneous measurements of current and intracellular Ca2+ concentration
      ([Ca2+]i) showed that the inward current correlated closely with transient
      increases in [Ca2+]i due to Ca2+ release from intracellular stores. The current
      could be blocked by 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS)
      but not by La3+, and it persisted in Ca(2+)-free/Na(+)-free solution. When intra-
      and/or extracellular Cl- concentrations were altered, the reversal potential of
      the current shifted according to the calculated Cl- -equilibrium potential,
      indicating that the current was carried primarily by Cl-. Another inward current
      was also activated by BK. This current was slower to activate, could be blocked
      by La3+, but was not blocked by DIDS. The time course of the slowly activated
      current correlated with the plateau phase of the BK-stimulated [Ca2+]i increase,
      which was similar to the behavior of a nonselective cation current reported
      previously. We propose that these two currents may contribute to the
      depolarizations and net inward currents induced by BK in this cell line.

PMID- 7529001
TI  - Acute compensation to abrupt occlusion of rat femoral artery is prevented by NO
      synthase inhibitors.
AB  - The hemodynamic significance of endothelium-derived relaxing factor (EDRF)
      mediated mechanisms in vascular responses to abrupt rat femoral artery occlusion
      was investigated. Temporary arterial occlusion was produced before and after
      inhibition of nitric oxide synthase by N omega-nitro-L-arginine methyl ester (L
      NAME) or NG-monomethyl-L-arginine (L-NMMA). Iliac artery blood flow and arterial
      pressures proximal and distal to the occlusion were measured. Normal vascular
      compensation included a return of resistance to preocclusion levels and a rise in
      distal pressure to a plateau within 5 min postocclusion. After treatment with L
      NAME and L-NMMA, postocclusion resistance remained elevated by 53 and 36%,
      respectively. Collateral dilation after occlusion, as indicated by the rise in
      distal pressure, was prevented by L-NAME but not L-NMMA. Increases in adrenergic
      tone and mean arterial pressure by phenylephrine did not prevent compensation,
      suggesting the effects of L-NAME and L-NMMA did not result from elevated
      sympathetic activation or pressure. The results are consistent with the
      hypothesis that the stimulated release of endothelium-derived relaxing factor
      mediates the acute vascular compensation to abrupt arterial occlusion.

PMID- 7529002
TI  - Renal effects of nitric oxide synthesis inhibition in cirrhotic rats.
AB  - In the present study, we have characterized the renal response to inhibition of
      endogenous nitric oxide (NO) synthesis [intravenous NG-nitro-L-arginine methyl
      ester (L-NAME) for 3 h] in anesthetized cirrhotic rats, with (ASC) and without
      (CIR) ascites, at doses that do not change blood pressure (BP). Administration of
      L-NAME induced opposite effects on water (UV) and sodium (UNaV) excretion in
      cirrhotic and control animals. Infusion of 1 microgram.kg-1.min-1 of L-NAME in
      CIR (n = 5) decreased renal plasma flow (RPF) at the end of the 3-h period,
      whereas UV, UNaV, and glomerular filtration rate (GFR) were unaltered. In
      contrast, infusion of L-NAME at 10 micrograms.kg-1.min-1 in six more CIR
      increased UV and UNaV significantly by the 1st h, without changes in BP or GFR,
      and these parameters remained elevated throughout the experiment. Infusion of 1
      microgram.kg-1.min-1 in ASC (n = 6) did not change BP or GFR but significantly
      enhanced UV and UNaV after the 1st h. These effects were prevented by
      pretreatment with L-arginine (0.1 mg.kg-1.min-1) in another group of ASC infused
      with 1 microgram.kg-1.min-1 of L-NAME. These results indicate that, in ASC and
      CIR cirrhotic rats, inhibition of NO synthesis at nonpressor does improves renal
      excretion of sodium and water via a decrease in tubular reabsorption. NO is an
      important mediator of the renal excretory and hemodynamic alterations of
      experimental liver cirrhosis.

PMID- 7529003
TI  - Hormonal, renal, and metabolic alterations during hypertension induced by chronic
      inhibition of NO in rats.
AB  - The evolution of renal excretory function and circulating vasoactive systems was
      studied during progressive increases in blood pressure (BP) induced in rats by
      oral administration of NG-nitro-L-arginine methyl ester (L-NAME; 5-30 mg/100 ml)
      for 5 wk. L-NAME induced a stepped elevation (P < 0.05) in BP levels without
      changing creatinine clearance, urine flow, or sodium excretion rate along the
      study. Reductions (P < 0.05) in plasma renin activity and plasma aldosterone
      concentration were found only during treatment with 30 mg/100 ml of L-NAME.
      Plasma norepinephrine and epinephrine concentrations were elevated (P < 0.05) in
      the last week of the study. Plasma concentrations of endothelin-1 and urinary
      excretion of prostaglandin E2, 6-ketoprostaglandin F1 alpha, and thromboxane B2
      were not significantly affected by L-NAME. Similarly, no changes in plasma
      concentrations of glucose, insulin, total cholesterol, or triglycerides were
      observed. In summary, during long-term administration of L-NAME, progressive
      increases in BP levels were observed without changes in either sodium excretion
      or enhanced circulating vasoconstrictor activity. Thus, it is likely that
      inhibition of synthesis of nitric oxide (NO) in the vasculature leads to an
      imbalance between the tonic relaxing action of NO and the influences of
      vasoconstrictor agents even when the latter remain at normal levels.

PMID- 7529004
TI  - Dopamine or transmitter release from rat carotid body may not be essential to
      hypoxic chemoreception.
AB  - In anesthetized, paralyzed, and ventilated rats, hypoxia or intracarotid cyanide
      excited the carotid chemoafferents, whereas intracarotid dopamine and tyramine
      inhibited the chemoafferent discharges. The inhibition was abolished by
      chlorpromazine without attenuating the hypoxic excitation. Comparably, the
      hypoxic excitation was not attenuated by the following: 1) inhibition of nitric
      oxide synthase with NG-nitro-L-arginine; 2) inhibition of heme oxygenase with
      zinc protoporphyrin IX; 3) antagonism of ATP receptors with reactive blue 2; 4)
      antagonism of cholinergic receptors with atropine or trimethaphan; 5)
      inactivation of adenosine with adenosine deaminase; and 6) blockade of glutamate
      receptors with kynurenate. Systemic administration of ethylene glycol-bis(beta
      aminoethyl ether)-N,N,N'N'-tetraacetic acid, in doses reversibly blocking
      sympathetic ganglionic transmission, was also without effect. Cyanide
      microinjection (0.05-0.5 nmol) into the petrosal but not nodose ganglion elicited
      a rapid dose-dependent elevation of arterial pressure. We conclude that
      excitation of the chemoreceptor afferents by hypoxia/cyanide cannot be attributed
      to release of these agents nor to others by Ca(2+)-dependent mechanisms. The
      results suggest that the afferent nerves themselves might function as oxygen
      detectors.

PMID- 7529005
TI  - Kinetics of processive nucleic acid polymerases and nucleases.

PMID- 7529006
TI  - One-hour downward capillary blotting of RNA at neutral pH.
AB  - This report describes a setup for the downward capillary blotting of RNA with the
      use of 10 x SSC as a transfer solution. The setup is composed of a stack of
      blotting papers, hybridization membrane, and agarose gel. Two layers of blotting
      paper connect the stack with two reservoirs containing transfer solution. Using
      this setup, blotting of RNA fragments (< 7.5 kb) can be completed in 1 h. If
      necessary, the blotting time can be expanded from 1 to 18 h without decrease in
      hybridization efficiency of RNA.

PMID- 7529008
TI  - Quantification and characterization of glycosaminoglycans at the nanogram level
      by a combined azure A-silver staining in agarose gels.
AB  - A rapid, sensitive, and nonradioactive method has been developed for the
      quantification and characterization of glycosaminoglycans. The method is based on
      the separation of different types of glycosaminoglycans in agarose gel and
      subsequent fixation and staining with the cationic dye azure A, followed by
      silver enhancement. Densitometric analysis of the silver deposition gives a
      linear response between 1 and 20 ng for chondroitin and dermatan sulfate and
      between 2 and 40 ng for heparan sulfate. The detection limit is about 250 pg. The
      staining procedure was applied for the quantification and characterization of
      glycosaminoglycans in human serum, urine, and lung and in mouse kidney glomeruli.
      It requires only 10 microliters serum, 2 microliters urine, and only a single
      cryosection in case of tissue. The method is at least as sensitive as staining
      with radioactive markers and about 200 times more sensitive than conventional
      glycosaminoglycan-staining methods.

PMID- 7529007
TI  - A ligand binding assay for E-selectin.
AB  - We describe here a cell-free ligand binding assay for E-selectin. The assay
      involves immobilizing soluble E-selection onto microtiter plates and incubating
      with 125I-labeled carcinoembryonic antigen (CEA) which carries the
      tetrasaccharide sialyl Lewis x (sLex). The bound CEA is eluted by ethylene glycol
      bis(beta-aminoethyl ether)-N,N,N',N',-tetraacetic acid and monitored by
      radioactivity. The binding is abolished by preincubation of either CEA with an
      anti-sLex antibody or E-selectin with a neutralizing anti-E-selectin antibody,
      indicating that this is an E-selectin/sLex-specific interaction. The binding is
      Ca2+ and pH dependent (the optimal pH at 7.0) and also requires sialic acid.
      Removal of sialic acid from CEA by neuraminidase digestion abrogates the binding.
      When the protein but not carbohydrate constituent of CEA was denatured by
      reduction and alkylation, the binding was partially eliminated, indicating that
      the interaction may also be dependent on either protein conformation or
      carbohydrate orientation. The assay is simple, sensitive, and comparable to other
      methods as indicated by an IC50 of 1 mM for sLex. Thus, the assay should be
      useful for screening antagonists and studying E-selectin structure/function.

PMID- 7529009
TI  - Identification of acid cysteine proteinase inhibitor (cystatin A) in the human
      thymus.
AB  - BACKGROUND: Acid cysteine proteinase inhibitor (ACPI, also called cystatin A) is
      a protein that is present in the epithelial cells of the skin and in the
      dendritic reticulum cells of lymphoid tissues. In this study the presence and
      cellular localization of ACPI in the thymus was investigated. METHODS: The
      cellular and topographical location of ACPI was immunohistochemically
      demonstrated in the normal thymus of man. RESULTS: ACPI was found in the cells of
      the Hassall's corpuscles and in many medullary cells. Most of these cells were
      epithelial cells, as shown by the results of immunohistochemical cytokeratin and
      epithelial membrane antigen stainings. Also, some individual cytokeratin negative
      but S-100 positive medullary reticular dendritic cells were stained with ACPI.
      CONCLUSIONS: The finding that ACPI is constantly present in the thymus at
      restricted and specific cellular locations leads to the suggestion that protease
      inhibitors may play a role in specific thymic functions.

PMID- 7529010
TI  - Distribution of transposable elements in arthropods.
AB  - Transposable elements of the DNA-mediated and RNA-mediated classes found in
      arthropods are briefly described and their distribution reviewed. The
      distribution patterns of DNA-mediated elements are extremely patchy and the
      principal cause appears to be the horizontal transfer of elements between host
      lineages. In the best documented case of mariner elements, these hosts can be in
      different orders of insects, classes of arthropods, and even other phyla of
      animals. RNA-mediated elements appear to undergo much longer periods of vertical
      evolution within host lineages, and evidence for their horizontal transfer
      remains scant. The evolutionary relationships of many of these transposons have
      recently been illuminated by phylogenetic analyses of the reverse-transcriptase
      enzymes of the RNA-mediated elements, and the recognition that the transposases
      of some of the DNA-mediated elements are distantly related to in the integrases
      of some of the RNA-mediated elements.

PMID- 7529011
TI  - Subunit specificity of mutations that confer resistance to nonnucleoside
      inhibitors in human immunodeficiency virus type 1 reverse transcriptase.
AB  - We constructed plasmid vectors that simultaneously express both the p66 and p51
      subunits of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase
      (RT) in Escherichia coli. These vectors allow us to generate HIV-1 RT
      heterodimers in which either the p66 or the p51 subunit has the wild-type
      sequence and the other subunit has a specific amino acid substitution. We used
      these vectors to express HIV-1 RT heterodimers containing several different amino
      acid substitutions reported to confer resistance to nonnucleoside inhibitors.
      Most of the amino acid substitutions conferred resistance to nonnucleoside
      inhibitors R86183 (TIBO) and TSAO-m3T only when present in the p66 subunit of the
      p66-p51 heterodimer; heterodimers that contained a wild-type p66 subunit and a
      mutant p51 subunit remained sensitive to the inhibitors. However, there was one
      mutation, E138K, that conferred drug resistance when the mutation was present in
      the p51 subunit. The corresponding heterodimer with the E138K mutation in the p66
      subunit and a wild-type p51 subunit remained sensitive to the inhibitors.
      Analysis of the three-dimensional structure of HIV-1 RT indicated that residue
      138 of the p51 subunit is in the nonnucleoside inhibitor-binding pocket while
      residue 138 of the p66 subunit is not. The mutagenesis results, combined with
      structural data, support the idea that the nonnucleoside inhibitors exert their
      effects by binding to a hydrophobic pocket in the RT heterodimer and that
      mutations which give rise to drug resistance directly interfere with the
      interactions between the nonnucleoside inhibitors and HIV-1 RT.

PMID- 7529012
TI  - Assessment of mycobacterial viability by RNA amplification.
AB  - We investigated whether the presence of intact RNA is a valuable indicator of
      viability of mycobacteria with Mycobacterium smegmatis. M. smegmatis was exposed
      to various concentrations of rifampin and ofloxacin suspended in broth for
      different periods of time. The NASBA nucleic acid amplification system was used
      because of its rapid, sensitive, and specific detection of 16S rRNA. During drug
      exposure, the viability of the mycobacteria, expressed by the number of CFU, was
      compared with the presence of 16S rRNA as determined by NASBA and with the
      presence of DNA coding for 16S rRNA as determined by PCR. Both NASBA and PCR were
      shown to have a detection limit of approximately 5 x 10(2) CFU/ml. The intensity
      of the NASBA signal corresponded well with the number of CFU, and the lack of
      NASBA signal coincided with a loss of viability, which was reached after 3 days
      of exposure to bactericidal concentrations of both drugs. The presence of
      mycobacterial DNA, as determined by the intensity of the PCR signal, and the
      viability of M. smegmatis were not related, but an increase in the number of
      cells and intensity of PCR signal correlated well. Bacterial viability may thus
      be assessed by a rapid, sensitive, and specific, and semiquantitative technique
      by using NASBA. This system of viability testing provides the potential for rapid
      evaluation of drug susceptibility testing.

PMID- 7529014
TI  - Biological and biochemical anti-HIV activity of the benzothiadiazine class of
      nonnucleoside reverse transcriptase inhibitors.
AB  - A series of benzothiadiazine derivatives were screened against the human
      immunodeficiency virus (HIV) and certain structure-activity relationships were
      defined for anti-HIV activity in this chemical class. The selected representative
      NSC 287474 was a highly potent inhibitor of HIV-induced cell killing and HIV
      replication in a variety of human cell lines, as well as in fresh human
      peripheral blood lymphocytes and macrophages. The compound was active against a
      panel of biologically diverse laboratory and clinical strains of HIV-1, including
      the AZT-resistant strain G910-6. However, the agent was inactive against HIV-2,
      and also against both nevirapine- and pyridinone-resistant strains (N119 and A17)
      of HIV-1, which are cross-resistant to several structurally diverse nonnucleoside
      reverse transcriptase inhibitors. The compound selectively inhibited HIV-1
      reverse transcriptase, but not HIV-2 reverse transcriptase. Combination of NSC
      287474 with AZT synergistically inhibited HIV-1-induced cell killing in vitro.
      The compound did not inhibit the replication of the Rauscher murine leukemia
      retrovirus or the simian immunodeficiency virus. The benzothiadiazine class of
      compounds represents a new active anti-HIV-1 chemotype within the diverse group
      of nonnucleoside reverse transcriptase inhibitors.

PMID- 7529013
TI  - Inhibition of Friend murine leukemia virus activity by guanosine/thymidine
      oligonucleotides.
AB  - Oligonucleotides consisting of only deoxyguanosine and deoxythymidine were stable
      in culture and were able to significantly inhibit Friend Murine Leukemia Virus
      (FMLV) production in acute cell culture assay systems. The oligonucleotides did
      not share homology with, or possess any complementary (antisense) sequence motifs
      to the FMLV genome. The guanosine/thymidine-containing oligonucleotides (GTOs)
      which demonstrated anti-FMLV activity in acute infection assays were synthesized
      with natural phosphodiester (PD) linkages (backbones). The observed antiviral
      activities of these oligonucleotides increased significantly when the PD backbone
      was replaced with a phosphorothioate (PT) backbone. Experiments designed to
      investigate a potential antiviral mechanism of action demonstrated that
      oligonucleotides tested were capable of blocking virus adsorption. In addition,
      GTOs with PD backbones were competitive inhibitors of FMLV reverse transcriptase
      (RT). When the same experiments were performed using oligonucleotides with PT
      backbones, all compounds tested demonstrated significant competitive inhibition
      of FMLV RT. The measured inhibitory activity of all compounds tested in culture
      assays was enhanced by at least a factor of 10 when the PD linkages were replaced
      with PT. The enhanced antiviral activity exhibited by the sulfur group on the
      oligonucleotide backbone, and the lack of any designed, sequence-specific
      interactions, suggest that a large percentage of the reported antiviral activity
      of oligonucleotides containing a phosphorothioate backbone is due to factors
      other than rationally designed, sequence-specific interactions. The ability of
      GTOs to inhibit FMLV in culture, potentially via a number of different
      mechanisms, makes this a class of compounds which warrants investigation as
      therapeutic agents to be used against retroviral infections.

PMID- 7529015
TI  - Inhibition of human immunodeficiency virus type 1 (HIV-1) replication by
      daphnodorins.
AB  - Three flavans, daphnodorins A, B and C isolated from Dahpne odora THUNB. were
      tested for their abilities to inhibit human immunodeficiency virus type 1 (HIV
      1(IIIB)) replication in MT-4 cells. The effective concentrations (EC50) of
      daphnodorins A, B and C against HIV-1-induced cytolysis were 0.26 +/- 0.08, 1.8
      +/- 0.6 and 3.6 +/- 0.5 micrograms/ml, respectively. Also these three compounds
      showed inhibitory effects of p24 antigen in human peripheral blood lymphocytes.
      As compared with 2',3'-dideoxycytidine 5'-triphosphate (DDC-TP), daphnodorin A
      and daphnodorin C had relatively weak inhibitory effects on the reverse
      transcriptase of HIV-1, while daphnodorin B did not show any inhibitory effect at
      concentrations up to 1000 micrograms/ml. These three compounds showed marked
      inhibitory effects on syncytium formation between HIV-1(IIIB)-infected and
      uninfected MOLT-4 (clone 8) cells at 3-30 micrograms/ml without inducing
      cytotoxicity. The concentrations of the compounds blocking syncytium formation
      were consistent with the effective concentrations (EC50) against HIV-induced
      cytolysis of MT-4 cells. These results, differing from reverse transcriptase
      inhibitors, suggest that the daphnodorins exert their anti-HIV-1 activity through
      inhibition of early events of viral replication including adsorption of the
      virions to the cells or the subsequent entry.

PMID- 7529016
TI  - Phylogenetic analysis of a highly specific association between ectosymbiotic,
      sulfur-oxidizing bacteria and a marine nematode.
AB  - The phylogenetic relationship of chemoautotrophic, sulfur-oxidizing,
      ectosymbiotic bacteria growing on a marine nematode, a Laxus sp. (formerly a
      Catanema sp.), to known endosymbionts and free-living bacteria was determined.
      Comparative 16S rRNA sequencing was used to investigate the unculturable nematode
      epibionts, and rRNA-targeted oligonucleotide hybridization probes were used to
      identify the ectosymbionts in situ. Both analyses revealed a remarkably specific
      and stable symbiosis. Unique hybridization of a specific probe to the
      ectosymbionts indicated that only one species of bacteria was present and growing
      on the cuticle of the nematode. Distance and parsimony methods used to infer
      phylogenetic trees both placed the nematode ectosymbionts at the base of a branch
      containing chemoautotrophic, sulfur-oxidizing endosymbionts of three bivalve
      families and of the tube worm Riftia pachyptila. The most closely related free
      living bacteria were chemoautotrophic sulfur oxidizers belonging to the genus
      Thiomicrospira. Furthermore, our results suggested that a second, only distantly
      related group of thioautotrophic endosymbionts has as its deepest branch surface
      colonizing bacteria belonging to the genus Thiothrix, some of which are capable
      of sulfur-oxidizing chemoautotrophic growth.

PMID- 7529018
TI  - 1C5 antigen: cancer-associated protein expressed by cervical adenocarcinomas and
      beta-casein.
AB  - The monoclonal antibody 1C5 reacts with an antigenic determinant present in 90%
      of the cases of adenocarcinoma of the uterine cervix. The antigen defined by the
      1C5 antibody exhibits immunological characteristics similar to those of skim milk
      (bovine buttermilk). 1C5-defined antigen obtained from tumor extract and skim
      milk binds specifically to wheat germ agglutinin (WGA) lectin. The 1C5-defined
      antigenic activity of a WGA lectin-bound fraction was eluted at 0.7-0.8 M NaCl
      off a Mono Q column. Use of an inhibition assay and a dot immunobinding assay
      revealed that the antigenic epitope defined by the 1C5 MoAb from skim milk exists
      within the first 28 amino acids of the beta-casein peptide.

PMID- 7529017
TI  - Renibacterium salmoninarum, the causative agent of bacterial kidney disease in
      salmonid fish, detected by nested reverse transcription-PCR of 16S rRNA
      sequences.
AB  - An assay based on reverse transcription and nested PCR amplification of
      hypervariable regions within the 16S rRNA sequence was used to specifically
      detect Renibacterium salmoninarum, the slowly growing causative agent of
      bacterial kidney disease in salmonid fish. This assay detected 1 to 10 bacteria
      per sample and took 1 to 2 days to perform. The assay was used to detect R.
      salmoninarum in ovarian fluid obtained from naturally infected fish. The assay
      was unreliable when it was used to examine kidney tissue.

PMID- 7529020
TI  - Effect of peptide acetylation on its interaction with antipeptide antibody.
AB  - The effects of trace acetylation on the contact sites in peptide-antibody binding
      have been investigated by using a label selection method. A 13-residue synthetic
      peptide having three lysines (LKLVEQQNPKVKL) corresponding to sequence position
      155-168 of beta 1,4-galactosyltransferase was used in this study. The four amino
      groups located throughout the peptide sequence, labeled appropriately, served as
      probing marker groups. The amino terminus region of the peptide was highly
      reactive to trace acetylation. Over 80% of the label appeared in the amino
      terminus region, most likely in the alpha-amino group due to its lower pK value.
      Interestingly, acetylation of Lys10 and Lys12 (carboxy terminal region) showed a
      selection for interacting with the antibody. This approach, using label selection
      affords high sensitivity and could be applicable for mapping antigen-antibody
      interaction site/s.

PMID- 7529021
TI  - Localization of stem cell factor (SCF) and c-kit mRNA in human placental tissue
      and biological effects of SCF on DNA synthesis in primary cultured
      cytotrophoblasts.
AB  - The supernatant of homogenized human placental tissues at early and late stages
      of pregnancy were found to contain 40-100 pg of stem cell factor (SCF)/mg of
      total protein by enzyme linked immunosorbent assay. When the SCF mRNA expression
      was examined by reverse transcriptase-polymerase chain reaction (RT-PCR), the
      secretory type and membrane-bound type SCF mRNA were detected in the human
      placental tissues in the early stages of pregnancy and in a human placental cell
      line;tPA30-1 cells. However, the secretory type SCF mRNA was predominant and
      membrane-bound type SCF mRNA was absent or very weak in the term placental
      tissues. When the distribution of SCF mRNA and c-kit mRNA in the placental
      tissues was examined by in situ hybridization, SCF mRNA was detected in the
      cytotrophoblast, the intermediate trophoblastic cell column and the stromal
      cells, while c-kit mRNA was detected in the cytotrophoblast and the intermediate
      trophoblastic cell column. Both c-kit and SCF mRNA were absent or very weak in
      the syncytiotrophoblasts. The supernatant of primary cultured cytotrophoblasts
      and tPA30-1 cells were found to contain SCF. In cytotrophoblasts in the early
      stage of pregnancy cultured in the presence of recombinant human secretory type
      SCF, DNA synthesis was increased depending on the SCF concentration. These
      findings indicate that SCF is a cytokine which promotes the growth of placental
      cells by the autocrine and paracrine mechanism.

PMID- 7529023
TI  - Reduction of ryanodine binding and cytosolic Ca2+ levels in liver by the
      immunosuppressant FK506.
AB  - The mechanism of action of the immunosuppressant FK506 in the liver was studied.
      The hypothesis was tested that FK506 exerts its effect in the liver by
      interacting with the ryanodine-binding Ca2+ release channel. Two types of
      experiments were carried out: (1) [3H]-ryanodine binding studies with isolated
      microsomal fractions, and (2) cytosolic-free Ca2+ ([Ca2+]i) measurements with the
      intracellular Ca(2+)-indicator fura-2. The inclusion of FK506 in the incubation
      medium significantly decreased the binding of [3H]-ryanodine to liver microsomes.
      The Bmax of binding in control experiments was 405 fmol/mg protein; the presence
      of FK506 decreased the Bmax to 157 fmol/mg protein. Measurements of [Ca2+]i in
      the presence and absence of FK506 showed a decrease in [Ca2+]i in the presence of
      FK506. The data support the notion that FK506 interacts with the ryanodine
      binding Ca2+ channel in the liver and suggest a critical role for the ryanodine
      binding Ca2+ channel in the hepatic responses to FK506. The interaction between
      FKBP-12 (FK506 binding protein) and the ryanodine-binding Ca2+ channel may be an
      essential link in the chain of events by which FK506 alters Ca(2+)-dependent
      cellular processes.

PMID- 7529024
TI  - Auditory integration training.

PMID- 7529022
TI  - Tumor necrosis factor-alpha induces the expression of carbonic anhydrase II in
      pancreatic adenocarcinoma cells.
AB  - TNF is a 17kD cytokine classically known for its cytotoxic effects on malignant
      cells. More recent cell culture studies demonstrated TNF induced cytostasis
      associated with the expression of a terminally differentiated phenotype. This was
      best characterized in malignant hematopoietic models, although a similar action
      on cells derived from solid tumors is now increasingly recognized. In the present
      study, six day exposure to TNF (40 ng/ml) stimulated morphologic changes in a
      human pancreatic adenocarcinoma cell line (HPAC), including increased cellular
      homogeneity, decreased nuclear to cytoplasmic ratio and detachment from the cell
      monolayer. Proliferation and DNA synthesis were reversibly inhibited while
      cellular viability was maintained. Parallel to the changes in morphology and
      growth was the delayed appearance of carbonic anhydrase II (CA II, E.C. 4.2.1.1),
      an accepted marker for pancreatic cells of ductal origin. A concomitant increase
      in the steady-state level of CA II mRNA was also observed over the time-course of
      TNF exposure. These results suggest a novel role for TNF in the induction of a
      more terminally differentiated ductal cell phenotype in a human pancreatic
      carcinoma model.

PMID- 7529019
TI  - Inducible nitric oxide synthase activity in myocardium after myocardial
      infarction in rabbit.
AB  - The activity of nitric oxide synthase (NOS) in infarcted and noninfarcted rabbit
      myocardium was determined. NOS activity, as measured by conversion of
      [14C]arginine to [14C]citrulline, was significantly higher in the infarcted area
      of myocardium (22.7 +/- 3.7 fmol/mg as compared to 7.67 +/- 1.0 in noninfarcted
      area). NOS activity within the area of risk remained on control level. Increased
      inducible NOS activity was observed on the first postoperative day and persisted
      for at least 14 days; it declined 3 weeks after infarction. Citrulline formation
      was inhibited by N-omega-nitro-L-arginine and N-omega-monomethyl-L-arginine The
      localization of NOS by monoclonal anti-NOS antibody indicates mononuclear
      cells/macrophages as the likely source of the enzyme. The concentrations of tumor
      necrosis factor-alpha and interleukin-1 beta were not increased in peripheral
      blood or myocardium.

PMID- 7529027
TI  - In vivo binding of human inter-alpha-trypsin inhibitor free heavy chains to
      hyaluronic acid.
AB  - In vivo binding of human inter-alpha-trypsin inhibitor to hyaluronate was
      investigated by immunoelectrophoretic techniques. Pathological synovial fluids
      and follicular fluids both contain high concentrations of soluble hyaluronate.
      Heavy chain epitopes of inter-alpha-trypsin inhibitor were firmly associated with
      the hyaluronate in synovial fluid and follicular fluid. The hyaluronate-bound
      inter-alpha-trypsin inhibitor epitopes did not cross-react immunologically with
      bikunin. Several hyaluronate-bound inter-alpha-trypsin inhibitor fragments with
      molecular masses in the range 120,000-30,000 Da were demonstrated by
      immunoblotting. Heavy chain 1 of inter-alpha-trypsin inhibitor was shown to
      associate with hyaluronate by amino acid sequence analysis of isolated
      hyaluronate-bound proteins. These data indicate that in vivo metabolism of inter
      alpha-trypsin inhibitor takes place in pathological synovial fluid and in ovarian
      follicular fluid shortly before ovulation.

PMID- 7529026
TI  - Channel active mammalian porin, purified from crude membrane fractions of human B
      lymphocytes and bovine skeletal muscle, reversibly binds adenosine triphosphate
      (ATP).
AB  - A new aspect of mammalian porin (mammalian VDAC = mammalian voltage-dependent
      anion channel) is presented: channel active VDAC binds adenosine triphosphate
      (ATP) in the absence of Ca2+. Channel active "Porin 31HL" or "Porin 31BM",
      enriched from crude membranes of human B lymphocytes or whole cell lysates of
      bovine skeletal muscle, respectively, was bound to a nine atoms spacer ATP
      agarose at pH 7.4 or 5.0 and reeluted from the resin by 10 mM ATP disodium salt.
      Furthermore, channel active "Porin 31BM" was labelled by [32P]ATP in a 1:1
      stoichiometric relation. Binding of ATP to human porin was confirmed by studying
      the interaction of the synthetic porin fragment Type-1/Ac-35, comprising the
      putative nucleotide binding site G Y G F G, with trinitrophenyl-ATP (TNT-ATP) by
      scanning fluorometry. Peptide/TNP-ATP complexes clearly show enhancement of
      fluorescence intensity and a spectral shift of the fluorescence maximum. In a
      control experiment, using a porin fragment lacking the putative nucleotide
      binding site, no change of fluorescence emission was observed. Further
      confirmation for ATP binding by human VDAC arose from an autoradiographic
      experimental approach: the porin fragment Type-1/Ac-35 could be labelled by
      [32P]ATP, while a second porin fragment ending immediately before the putative
      nucleotide binding site could not; nor could a synthetic non porin peptide.

PMID- 7529025
TI  - Nonradiometric ELISA-based quantitation and validation of polymerase chain
      reaction-amplified DNA, including detection of point mutations, without allele
      specific amplification, or ligation.
AB  - We describe two simple novel procedures, one direct and the other involving
      hybridization, for the enzyme-linked immunosorbent assay (ELISA)-based detection,
      quantitation, and validation of polymerase chain reaction (PCR)-amplified DNA.
      Both procedures are applicable to any PCR reaction, and do not require specially
      synthesized or enzyme-tagged oligonucleotides. We obtained accurate quantitation
      of PCR-amplified human cc10kDa cDNA with a sensitivity of about 0.6 fmoles. This
      cDNA was also used to detect single-base insertions, deletions, and substitutions
      specifically. Additionally, we could readily distinguish zinc-finger Y chromosome
      specific genomic sequences in mixtures of male and female cells and normal and
      mutant cystic fibrosis transmembrane conductance regulator (CFTR) gene sequences
      in crude fibroblast lysates. To our knowledge, this is the first report of point
      mutation detection in solution by ELISA without allele-specific amplification or
      ligation. These novel procedures have vast potential for basic and clinical
      applications, including gene expression studies, rapid screening of genetic
      diseases, detection of oncogene and anti-oncogene mutations, and identification
      of pathogens (e.g., HIV-1) in clinical specimens.

PMID- 7529029
TI  - In situ expression of the cell adhesion molecules in bronchial tissues from
      asthmatics with air flow limitation: in vivo evidence of VCAM-1/VLA-4 interaction
      in selective eosinophil infiltration.
AB  - Eosinophils play a critical role in the pathogenesis of bronchial asthma by
      releasing various mediators. To understand the mechanisms of eosinophil migration
      to the site of inflammation, we examined the expression of adhesion molecules in
      the bronchial tissues of asthmatic subjects with air flow limitation. By
      immunohistochemical analysis, Mac-1, LFA-1, and VLA-4 were strongly positive in
      eosinophils and mononuclear cells infiltrated in the bronchial mucosa and
      submucosa. Their number was significantly increased compared with those in
      control tissue. Immunolocalization for ICAM-1, the ligand of Mac-1 and LFA-1, was
      detected in the endothelial cells of capillaries and venules, in the mononuclear
      cells in submucosa, and in the basal layer of the epithelium. Endothelial cells
      in capillaries and venules were also strongly positive for VCAM-1, the ligand of
      VLA-4. Immunolocalization for E-selectin was detected in some endothelial cells
      in capillaries and venules in bronchial submucosa, whereas there were very few
      positive cells in the bronchial tissues from control subjects. In situ
      hybridization demonstrated ICAM-1 mRNA expression in the endothelial cells and
      mononuclear cells in bronchial submucosa. Immunoelectron microscopy for ICAM-1,
      VCAM-1, and E-selectin demonstrated de novo synthesis of these molecules and
      their expression along the luminal cell membrane of endothelial cells. These
      results suggested that ICAM-1, VCAM-1, and E-selectin were newly synthesized
      prior to spontaneous asthma attacks, and that their expression, particularly that
      of VCAM-1, may play a key role in eosinophil infiltration into the airway.

PMID- 7529028
TI  - Tumor necrosis factor alpha modulates mitogenic responses of human cultured
      airway smooth muscle.
AB  - Airway wall remodeling, including hyperplasia of airway smooth muscle, is
      regarded as an important contributor to airway hyperresponsiveness in asthmatic
      patients. The effects of the proinflammatory cytokine, tumor necrosis factor
      alpha (TNF alpha) on the mitogenic responses of human cultured airway smooth
      muscle have been investigated. Lower concentrations of TNF alpha (0.3 to 30 pM)
      had a small, delayed (48-h incubation), stimulatory effect on DNA synthesis that
      was blocked by dexamethasone (1 microM), aspirin (100 microM), or primaquine (30
      microM) pretreatment, indicating that this effect was secondary to the release of
      cyclooxygenase products. TNF alpha (300 pM; 24- to 48-h incubation) alone had no
      effect on cell number or DNA or protein synthesis, but markedly reduced the
      stimulatory effects of thrombin (0.3 U/ml). TNF alpha (300 pM) also inhibited
      mitogenic responses to fetal calf serum (10%), epidermal growth factor (300 pM),
      and the thromboxane A2 mimetic U46619 (100 nM), indicating a nonselective effect.
      The inhibitory effects of TNF alpha (300 pM) were not blocked by pretreating the
      cells with the cyclooxygenase inhibitor aspirin (100 microM), the 5-lipoxygenase
      inhibitor CGS 8515 (3 microM), or the nitric oxide synthase inhibitor nitro
      iminoethyl-L-ornithine (100 microM), suggesting that neither arachidonic acid
      metabolites nor nitric oxide were mediators of the inhibitory effect. The
      phospholipase A2 inhibitor primaquine (30 microM) had no effect on the inhibitory
      responses to TNF alpha, whereas the anti-inflammatory steroid dexamethasone (1
      microM) prevented TNF alpha inhibition of mitogenic responses. Thus,
      concentrations of TNF alpha, within the range detected in bronchoalveolar lavage
      fluid from asthmatics, suppress mitogenic responses by a mechanism that is
      sensitive to inhibition by anti-inflammatory steroids, but does not appear to
      involve established targets for modulation by steroids, including arachidonic
      acid metabolism or induction of nitric oxide synthase.

PMID- 7529030
TI  - Release of hydrogen peroxide in response to hypoxia-reoxygenation: role of an
      NAD(P)H oxidase-like enzyme in endothelial cell plasma membrane.
AB  - The dynamics and mechanisms of extracellular release of hydrogen peroxide (H2O2)
      from bovine pulmonary artery endothelial cells (EC) subjected to anoxia, hypoxia,
      and hypoxia followed by reoxygenation were examined using various inhibitors of
      enzymatic systems in intact cells and by direct measurement of H2O2 production
      from isolated EC plasma membranes. Extracellular H2O2 was measured with a
      fluorometric assay. EC exposed to hypoxia (3% O2) and anoxia (0% O2) released
      less H2O2 (29.6 +/- 1.3% and 4.2 +/- 0.7%, respectively) compared with EC exposed
      to normoxia (20% O2). The extracellular release of H2O2 from EC previously
      exposed to hypoxia for 24 h increased immediately after reoxygenation (20% O2) to
      272 +/- 48%, as compared with EC exposed continuously to normoxia (100% release).
      Inhibition of xanthine oxidase (XO) by allopurinol did not reduce the release of
      H2O2 from cells exposed to normoxia or hypoxia followed by reoxygenation.
      Furthermore, inhibitors of cyclooxygenase (indomethacin), phospholipase A2
      (quinacrine and chlorpromazine), nitric oxide synthase (L-arginine analogs), the
      mitochondrial electron transport chain (rotenone and cyanide), and cytochrome P
      450 (methoxypsoralen) had no or minimal effect on this release. On the other
      hand, inhibitors of protein kinase C (calphostin and staurosporine) and NADPH
      oxidase (diphenyliodonium) reduced the release of H2O2 from EC in a dose
      dependent manner in both exposure groups. In separate experiments, plasma
      membranes isolated from EC were found to produce H2O2 in the presence of NADH or
      NADPH as electron donors. This was inhibited by diphenyliodonium but not by
      allopurinol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529033
TI  - Tryptophan concentrations increase in cerebrospinal fluid and blood after
      zidovudine treatment in patients with HIV type 1 infection.
AB  - Cerebrospinal fluid (CSF) and blood concentrations of indoleamines and
      catecholamines were analyzed in 14 HIV-1-seropositive individuals before
      antiviral treatment with zidovudine, after 3-14 months of treatment, and, in 8 of
      the patients, also after 14-30 months. The median pretreatment concentrations of
      tryptophan in CSF and blood were low (224 ng/ml and 6.0 micrograms/ml,
      respectively), but an increase in these values by an average of 40% in CSF and
      23% in blood was seen after 3-14 months of zidovudine treatment (p < 0.01) and
      remained undiminished after 14-30 months of treatment. No significant change was
      observed in the 5-hydroxytryptamine (5-HT, serotonin) level in blood or in the
      CSF concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) and
      the dopamine metabolite homovanillic acid (HVA). The CSF concentrations of the
      noradrenalin metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) had decreased by
      12% on average (p < 0.01) by the time of the second follow-up, that is, after 14
      30 months of zidovudine treatment. A decrease in neopterin during antiretroviral
      treatment correlated with an increase in tryptophan (p < 0.01). The data suggest
      that an association between decreased immune stimulation and reduced tryptophan
      degradation in patients treated with zidovudine.

PMID- 7529031
TI  - Regulation of the insulin-like growth factor system during normal rat lung
      development.
AB  - Insulin-like growth factor (IGF)-I and IGF-II are small peptide growth factors
      that interact with a specific membrane receptor, the type 1 IGF receptor, to
      stimulate cellular proliferation and/or differentiation. The actions of these
      growth factors and their availability to their receptors are modulated by
      specific binding proteins, IGF binding protein (IGFBP)-1 through -6, which
      together with the IGFs and IGF receptors form the IGF system. We have analyzed
      RNA extracted from fetal (gestation day 16 [E16] through 22 [E22]) and adult (60
      day-old) rat lung for expression of each component of the IGF system. IGF-I and 
      II RNAs are expressed throughout fetal development. IGF-I mRNA remained
      relatively constant in fetal and adult lung, whereas IGF-II RNA decreased in
      later gestation to levels below detection by Northern analyses in adult lung.
      Type 1 IGF receptor expression varied little through all ages studied, whereas
      the type 2 IGF receptor RNA displayed developmental regulation with a decline in
      expression with advancing age. IGFBP-1 transcripts were not detected in fetal or
      adult lung. IGFBP-2 RNA was expressed from E16 to E22, although its abundance
      decreased in late gestation and in adult lung, with the lowest levels of
      expression on day E22. IGFBP-3, -4, and -5 had similar profiles of RNA abundance,
      with fetuses at ages E21 and E22 displaying higher levels of transcript abundance
      as compared with those aged E17 to E20; the lowest RNA abundance was seen at
      E20.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529034
TI  - Mechanism of enzyme inhibition mediated by anti-reverse transcriptase antibodies
      from HIV type 1-infected individuals.
AB  - We have examined the mechanisms of reverse transcriptase (RT) inhibition mediated
      by anti-RT antibodies, isolated by affinity chromatography, from four HIV-1
      positive individuals. In kinetics assays, anti-RT immunoglobulin (Ig) obtained
      from three of the sera mediated a noncompetitive type of inhibition against
      template primer; two of these three also mediated noncompetitive inhibition with
      respect to deoxyribonucleoside triphosphate. Such inhibition did not require that
      the Ig be preincubated with RT prior to the addition of reaction components. In
      contrast, a more complicated pattern of inhibition was exhibited by anti-RT Ig
      from the fourth serum. Preincubation of this Ig with enzyme markedly enhanced the
      inhibition. The results demonstrate that the specificities of RT-inhibiting
      antibodies vary among HIV-1-infected individuals, but that one prevalent
      mechanism of inhibition involves interactions with epitopes outside of the enzyme
      active site.

PMID- 7529032
TI  - Enzymatic properties of two mutants of reverse transcriptase of human
      immunodeficiency virus type 1 (tyrosine 181-->isoleucine and tyrosine 188-
      >leucine), resistant to nonnucleoside inhibitors.
AB  - A number of structurally diverse compounds have been shown to be potent
      inhibitors of the DNA polymerase activity of human immunodeficiency virus (HIV-1)
      reverse transcriptase (RT). The compounds can be grouped into two broad classes:
      nucleoside analogs and nonnucleoside inhibitors. The nonnucleoside inhibitors are
      quite specific for the polymerase activity of HIV-1 RT; they do not affect the
      polymerase activity of HIV-2 RT or the ribonuclease H (RNase H) activity of
      either HIV-1 RT or HIV-2 RT. Structural, biochemical, and genetic analyses showed
      that this group of inhibitors binds in a hydrophobic pocket near the polymerase
      active site. Mutations in amino acids that line this hydrophobic pocket, for
      example at tyrosine 181, tyrosine 188, or lysine 103, lead to enzymes that are
      resistant to the nonnucleoside inhibitors. We have investigated the enzymatic
      properties of two mutants of HIV-1 RT in which residues 181 and 188 were replaced
      by the corresponding amino acids in HIV-2 RT (tyrosine 181-->isoleucine and
      tyrosine 188-->leucine). The two tyrosine mutants closely resemble the wild-type
      HIV-1 RT in almost all the catalytic functions tested, including the heat
      stability, sensitivity of the DNA polymerase activity to inhibition by
      deoxynucleoside analogs, inhibition by the zinc chelator o-phenanthroline, and
      the Km values calculated for the DNA polymerase activity. There is, however, a
      slight difference in the effect of orthophenanthroline on the RNase H activity.
      In addition, there is a subtle disparity in the fidelity of DNA synthesis
      (analyzed by a mispair extension assay), thus indicating that these mutant RTs
      are not likely to confer any selective advantages or disadvantages to the variant
      virions over wild-type virus.

PMID- 7529035
TI  - Monoclonal antibody-mediated inhibition of RNA binding and annealing activities
      of HIV type 1 nucleocapsid protein.
AB  - Retroviral nucleocapsid (NC) proteins are highly basic, with one or two zinc
      fingers, and are required for virion formation, genomic RNA dimerization and
      packaging, and replication primer tRNA annealing to the viral RNA. We report here
      the first characterization of monoclonal antibodies directed against a retroviral
      nucleocapsid protein and their use to study the structure-function relationships
      of the nucleocapsid protein NCp7 of HIV-1. Four anti-NCp7 monoclonal antibodies
      (MAbs) have been generated by using NCp7 of HIV-1. The epitope targets of these
      MAbs were mapped using ELISA and BIAcore techniques. Whereas three of them are
      specific for epitopes located in the N and C termini of NCp7, the fourth one
      appears to be conformation specific. Interestingly, only two of these MAbs, the
      conformation-specific one and the MAb recognizing an N-terminal epitope are able
      to inhibit the RNA-binding and annealing activities of NCp7 as well as strong
      stop DNA synthesis in vitro. The binding of the two other MAbs onto NCp7 either
      has no effect or enhances the NCp7-RNA interactions. These MAbs also display a
      differential recognition of the Gag polyprotein precursor, which makes them
      useful tools for studying NC protein maturation in the course of virion
      morphogenesis.

PMID- 7529036
TI  - Expression of alpha-fetoprotein and interleukin 2 receptors and impairment of
      membrane fluidity in peripheral blood mononuclear cells from AIDS and related
      syndromes.
AB  - We have previously shown that the expression of alpha-fetoprotein (AFP) receptors
      is impaired in mitogen-activated peripheral blood mononuclear cells (PBMCs) from
      HIV+ individuals and that this novel abnormality reflects an unusual
      proliferation response of PBMCs to mitogenic stimuli. Here we comparatively
      analyze, in PBMCs from patients with AIDS and related syndromes, (1) changes in
      membrane fluidity, measured as the cholesterol/phospholipid ratio (CH/PL), and
      (2) changes in the expression of AFP receptors and of the alpha chain of IL-2
      receptor (TAC antigen). Relative to normal cells, the expression of AFP and IL-2
      receptors appeared considerably reduced in AIDS-related complex (ARC) and AIDS
      patients. In asymptomatic HIV+ individuals the amount of AFP receptors was within
      the normal range, whereas that of IL-2 receptors increased twice. CH/PL ratios
      were significantly lower in PHA-activated than in quiescent PBMCs from healthy
      donors, which implies a gain in membrane fluidity. For seropositive groups, no
      statistically significant changes in CH/PL ratios were appreciated on PHA
      activation. Nevertheless, in HIV+ asymptomatic individuals, the CH/PL ratio of
      quiescent PBMCs resembled that of PHA-activated PBMCs from healthy donors,
      suggesting that quiescent PBMCs are in a partially activated or "preactivated"
      status. With the worsening of the disease, toward ARC and AIDS stages, however,
      quiescent PBMCs from these groups showed a considerable loss in membrane
      fluidity, evidenced by elevated values of the CH/PL ratio. This radical change
      strongly suggest a severe alteration of the lipid metabolism in these
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529038
TI  - Aprotinin to decrease bleeding and intraoperative blood transfusion requirements
      during descending thoracic and thoracoabdominal aortic aneurysmectomy using
      cardiopulmonary bypass.
AB  - The purpose of this retrospective study was to assess the efficacy of aprotinin,
      an antifibrinolytic agent, in reducing bleeding and blood transfusion
      requirements in patients undergoing descending thoracic or thoracoabdominal
      aortic aneurysmectomy using cardiopulmonary bypass (CPB). Sixty-nine consecutive
      patients underwent thoracic or thoracoabdominal aneurysmectomy using CPB in a 2
      year period. None of the 29 patients operated on in 1990 (group 1) received
      aprotinin, whereas all 40 patients operated on in 1991 (group 2) were placed on a
      high-dose regimen of aprotinin. There were no significant differences between the
      two groups. Administration of aprotinin was associated with a decrease in CPB
      time (p = 0.02), surgical duration (p = 0.05) and intraoperative blood loss (p =
      0.008) as well as a reduction in intraoperative packed red cells (p = 0.01), Cell
      Saver units (p = 0.05), fresh-frozen plasma units (p = 0.002), and platelet
      concentrate (p = 0.01) requirements. These data suggest that aprotinin is
      effective in reducing bleeding and blood transfusion requirements during
      descending thoracic or thoracoabdominal aortic aneurysmectomy using CPB.

PMID- 7529039
TI  - Hospice care in motor neurone disease.
AB  - Motor neurone disease is not automatically linked in people's minds with
      palliative care and the hospice movement, but an increasing number of people with
      the condition are benefiting from the services offered by hospices. The authors
      review what these services entail, and explain how they can help patients and
      families cope with this distressing illness.

PMID- 7529040
TI  - The drawings of children and young people with Down's syndrome: a case of delay
      or difference?
AB  - This study compared the performance of 29 children and young people with Down's
      Syndrome with the performance of 29 verbal-mental-age-matched children without
      learning difficulties on four drawing tasks and four picture-selection tasks. All
      eight tasks involved the graphic depiction of a perceptually-present array in
      which one object was partially occluded by another object. It was found that all
      participants performed better on the picture-selection tasks than on the drawing
      tasks, and that the individuals with Down's Syndrome performed significantly
      worse than the children without learning difficulties on all eight tasks.
      However, it was also found that the performance of the children without learning
      difficulties correlated strongly with their verbal mental age, but that the
      performance of the individuals with Down's Syndrome did not show the same
      correlation with verbal mental age. Other systematic differences between the
      drawings of the individuals with Down's Syndrome and those of the children
      without learning difficulties also occurred. The findings suggest that the
      drawing development of children and young people with Down's Syndrome may not
      just be delayed relative to that of children who do not have learning
      difficulties but may exhibit a qualitatively different pattern.

PMID- 7529037
TI  - The pharmacology of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA)/kainate antagonists and their role in cerebral ischaemia.
AB  - The development of selective, systemically active alpha-amino-3-hydroxy-5-methyl
      4-isoxazole propionate (AMPA)/kainate antagonists over the last 4 years has
      enabled the role of this excitatory amino acid receptor subtype to be scrutinised
      in the different models of ischaemia. The animal models of cerebral ischaemia can
      be subdivided into two major categories: focal ischaemia, in which the resulting
      infarct resembles the clinical condition of stroke; and models of severe
      forebrain ischaemia, in which there is delayed neuronal degeneration of
      hippocampal CA1 neurones. The neuropathology in the latter models resembles the
      clinical condition seen following a cardiac arrest, for example. It is well
      established that N-methyl-D-aspartate (NMDA) antagonists such as MK-801, 3-(2
      carboxypiperazine-4-yl)-propenyl-1-phosphonate (CPPene), DL-(E)-2-amino-4-methyl
      5-phosphono-3-pentanoic acid (CGP 37849), and N-(1-naphthyl)-N'-(3-ethylphenyl)
      N'-methylguanidine hydrochloride (CNS 1102) are neuroprotective in animal models
      of focal ischaemia. However, in models of severe forebrain ischaemia NMDA
      antagonists produced only partial protection. The discovery of 2,3-dihydroxy-6
      nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX) as a systemically active AMPA
      receptor antagonist enabled the role of this receptor subtype in ischaemia to be
      investigated. NBQX was shown to be neuroprotective against delayed neuronal
      degeneration of hippocampal CA1 neurones in animal models of severe forebrain
      ischaemia. Recent studies have demonstrated that NBQX administration can be
      delayed by up to 12 h and amelioration of delayed neuronal degeneration of
      hippocampal CA1 neurones can still be seen. NBQX has also been shown to be
      neuroprotective in animal models of permanent and temporary middle cerebral
      artery occlusion. 1-(Aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3
      benzodiazepine (GYKI 52466), a systemically active noncompetitive AMPA/kainate
      antagonist, was neuroprotective against focal ischaemia but was unable to
      attenuate hippocampal CA1 neuronal degeneration. Whilst the newer compounds such
      as (3SR,4aRS,6RS,8aRS)-6-[2-(1H-tetrazol-5-yl )-ethyl]-1,2,3,4,4a,5,6,7,8a
      decahydroisoquinoline-3-carboxylic acid (LY 215490) and 6-(1-imidazolyl)-7
      nitroquinoxaline-2,3(1H,4H)-dione (YM900) have been demonstrated to be
      neuroprotective in focal ischaemia models, there is still a lack of information
      with regard to their efficacy in models of severe forebrain ischaemia. It appears
      from initial studies that AMPA/kainate antagonists have a better behavioural
      profile than NMDA antagonists in terms of a lack of phychostimulant and
      phychotomimetic effects. However, these antagonists have their own problems in
      that they cause severe depression of glucose utilisation in the central nervous
      system at neuroprotective doses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7529041
TI  - Analysis of androgen receptor DNA reveals the independent clonal origins of
      uterine leiomyomata and the secondary nature of cytogenetic aberrations in the
      development of leiomyomata.
AB  - Uterine leiomyomata are thought to be monoclonal neoplasms. Accordingly,
      investigations of clonality with G6PD isoforms used as a marker for X chromosome
      inactivation have suggested independent origins for multiple tumors within
      individual uteri. However, results from a recent study assessing methylation
      differences between DNA of active and inactive X chromosomes have been
      interpreted to suggest that multiple tumors may arise from a common precursor. We
      have examined the clonality of 36 leiomyomata from 16 patients by analyzing X
      chromosome inactivation as indicated by the methylation status of the X-linked
      androgen receptor gene. As shown by this assay, all informative leiomyomata were
      monoclonal in origin. In patients with multiple leiomyomata, a random
      distribution of inactivation between the X homologs was noted, consistent with an
      independent origin of each tumor. Cytogenetic analysis was also performed on
      short-term cell cultures of 27 of the 36 tumors. In each of two tumors that had
      both cells with a clonal karyotypic abnormality and karyotypically normal cells,
      DNA prepared from short-term cultures showed a monoclonal pattern of X
      inactivation identical to that of the leiomyoma from which they were derived.
      These data suggest that karyotypically normal cells present in short-term
      cultures of uterine leiomyomata are part of the tumor clone, and that clonal
      expansion of tumor cells precedes the development of cytogenetic aberrations.

PMID- 7529042
TI  - Loss of heterozygosity on the short arm of chromosome 3 in mesothelioma cell
      lines and solid tumors.
AB  - Cytogenetic analysis of mesothelioma cell lines and solid tumors has documented
      non-random chromosomal abnormalities on the short arm of chromosome 3 from 3p14
      to 3p25. We therefore examined nine mesothelioma cell lines, their corresponding
      tumors, and 15 additional mesothelioma tumors for loss of heterozygosity on 3p
      from 3p13 to 3p25.5 by polymerase chain reaction and restriction fragment length
      polymorphism analysis at 8 loci: D3S3, D3S30, D3S6, D3S2, D3S32, D3F15S2, THRB,
      and VHL. Loss of heterozygosity was documented by loss of one of two alleles in
      the tumor DNA whose corresponding normal DNA was heterozygous and was documented
      in four of nine mesothelioma cell lines and six of 15 mesothelioma tumors or a
      total of 42% of the mesotheliomas evaluated. This study suggests the involvement
      of a gene on the short arm of chromosome 3 in the development of mesotheliomas.

PMID- 7529043
TI  - Molecular heterogeneity at the breakpoints of smaller 20q deletions.
AB  - Deletions of the long arm of chromosome 20 [del(20q)] are recurring abnormalities
      in patients with myeloid disorders. Although variable in size, these deletions
      are usually interstitial. With the object of defining a commonly deleted region
      for smaller 20q deletions, we used quantitative Southern blot analysis
      complemented by restriction fragment length polymorphism (RFLP) analysis to
      determine the copy number at 15 loci spanning 20q. The proximal breakpoints of
      three such deletions were found to separate HCK and the growth hormone releasing
      factor (GHRF) locus near the centromeric boundary of band 20q11.2. The distal
      breakpoints were localized to the vicinity of the D20S22 locus in band q13.1. A
      candidate tumor suppressor gene, RBL2, and the SRC oncogene were both located
      within the commonly deleted region. Six loci in terminal region q13.2-q13.3 were
      conserved on these del(20q) chromosomes, thereby confirming that the deletions
      were interstitial. Molecular heterogeneity at one and possibly both deletion
      breakpoints rules out the pathological involvement of loci at these sites.
      Instead, loss of a tumor suppressor locus from within the commonly deleted region
      may contribute to deregulated hemopoiesis.

PMID- 7529044
TI  - Consistent chromosomal losses in head and neck squamous cell carcinoma cell
      lines.
AB  - Clonal chromosomal abnormalities were characterized in nine cell lines
      established from squamous cell carcinomas of the head and neck. Aneuploidy was a
      common feature; one cell line was near-diploid, three were near-triploid, four
      were near-tetraploid, and one cell line showed extensive variation in chromosome
      numbers. Consistent numerical abnormalities included loss of the sex chromosomes
      in six cell lines, losses of chromosomes 2 and 21 in six and five cell lines,
      respectively, and gain of chromosome 20 in five cell lines. Recurrent structural
      rearrangements included del(10)(q22-q26) (seven cell lines), i(5)(p10) (six cell
      lines), i(8)(q10) (six cell lines), add(19)(q13) (six cell lines), del(4)(q21
      q31.3) (five cell lines), i(3)(q10) (four cell lines), del(12)(p11.1-p12) (four
      cell lines), and add (18)(q21-q23) (four cell lines). Other changes were noted in
      lower frequencies. Loss of specific regions on chromosomes 2, 3p, 4q, 5q, 8p,
      10q, 12p, 18q, 19q, and 21 suggests that they may represent sites of putative
      tumor suppressor genes, loss of which may play a role in the pathogenesis of
      squamous cell carcinomas of the head and neck. Alternatively, gain of chromosomal
      region 3q, 5p, and 8q due to isochromosome formation suggests that more than one
      mechanism is involved in malignant transformation. Cytogenetic evidence of gene
      amplification was found in two cell lines; as an hsr(11)(q13) in one and as dmins
      in the other. The clonal karyotypes of four cell lines were compared with those
      of their respective primary tumors. In all cell lines, clonal evolution had
      occurred, with loss of some rearrangements present in the primary tumors or the
      gain of additional abnormalities.

PMID- 7529045
TI  - Detection of numerical and structural chromosome abnormalities in pediatric germ
      cell tumors by means of interphase cytogenetics.
AB  - In contrast to the cytogenetically well characterized testicular germ cell tumors
      (GCT) in adults, reports on cytogenetic studies in pediatric GCT are scarce. The
      presence of an i(12p) and numerical abnormalities involving chromosome 12 are the
      most frequent cytogenetic changes in GCT of adults. We have performed in situ
      hybridization (ISH) studies on paraffin sections and on isolated nuclei of 13
      pediatric GCT with particular emphasis on those chromosome abnormalities that are
      common in adult GCT. These include numerical and structural abnormalities of
      chromosomes 1 and 12 as well as numerical deviations of chromosomes 8, 10, X, and
      Y. The histological subsets of the tumors investigated included two dysgerminomas
      (DGE), one seminoma (SE), two embryonal carcinomas (EC), four mixed and two pure
      yolk sac tumors (YST), and one undifferentiated (IT) and one differentiated
      teratoma (TD). Similar to the GCT in adults, additional copies of chromosome 12
      were the most frequently observed numerical abnormalities. In contrast to the
      findings in adult GCT, changes in the size of the pericentromeric hybridization
      signals of chromosome 12, suggesting the presence of i(12p) chromosomes, were
      found in only two cases. No chromosome abnormalities were found in the pure TD or
      in the TD cells of mixed tumors containing a YST component. In the YST portion,
      however, Ip deletions and/or numerical chromosome changes were present.
      Surprisingly, deletions of the short arm of chromosome I, del(I)(p36.3), were
      frequent in pediatric GCT and were the sole abnormality detected in two cases.
      The Ip36 deletions were present in all stage-IV EC and YST investigated and were
      absent in the relatively benign TD and in one YST stage-I. Therefore, Ip36
      deletions may have value as a prognostic marker in pediatric GCT.

PMID- 7529046
TI  - The two genes generating RET/PTC3 are localized in chromosomal band 10q11.2.
AB  - PCR analysis of DNA from a selected panel of human-rodent somatic cell hybrids
      and fluorescent in situ hybridization (FISH) analysis allowed us to localize the
      human ELE1 gene. This previously uncharacterized gene is fused with the tyrosine
      kinase (tk) domain of the RET proto-oncogene to generate the oncogenic sequence
      RET/PTC3, thus providing a third example of RET oncogenic activation in papillary
      thyroid carcinomas. ELE1 was localized to band 10q11.2, the subband where RET
      also maps, at a minimum distance of more than 500 kb from the proto-oncogene. The
      fusion event corresponding to the rearrangement reciprocal to that leading to the
      formation of RET/PTC3 was also identified and characterized. The karyotype of two
      RET/PTC3 positive tumors did not show any evidence of chromosome 10
      abnormalities. The data indicate that a cytogenetically undetectable paracentric
      inversion within 10q11.2 generates RET/PTC3.

PMID- 7529048
TI  - The insulin-like growth factor I receptor gene is the target for the 15q26
      amplicon in breast cancer.
AB  - We report the amplification and overexpression of the IGFIR (insulin-like growth
      factor I receptor) gene in primary breast cancers with an amplification of band
      15q26. The involvement of IGFIR, which may vary in frequency from 2-3% in
      unselected tumor series to more than 10% in breast cancers with hsr, may
      represent an important event in tumor progression.

PMID- 7529047
TI  - Detailed deletion mapping of chromosome segment 17q12-21 in sporadic breast
      tumours.
AB  - Linkage studies have indicated that a gene on chromosome arm 17q, designated
      BRCA1, confers susceptibility to familial breast and ovarian cancer. To
      investigate the possible involvement of the BRCA1 gene in sporadic breast cancer
      we have analysed loss of heterozygosity (LOH) in a panel of 100 sporadic primary
      breast tumours using 10 PCR-based polymorphic markers from 17q12-21. Allele
      losses were detected in 40 of 100 tumours informative for at least one of the
      markers analysed. Of these 40 deleted tumours, 27 showed partial or interstitial
      loss on 17q. The pattern of LOH in the tumours with partial or interstitial LOH
      revealed three putative distinct deleted regions on 17q12-21. The first lies on
      the proximal long arm between D17S250 and THRA1; the second one lies between
      D17S776 and D17S579, the region containing the BRCA1 gene; and the third is
      telomeric to D17S733. The most frequently deleted region overlaps with the
      minimal region containing the BRCA1 gene, suggesting that this gene might also be
      associated with the development or progression of a proportion of sporadic breast
      tumours.

PMID- 7529049
TI  - The Heregulin gene can be included in the 8p12 amplification unit in human breast
      cancer.
AB  - The Heregulin (HGL) gene, encoding a ligand for a member of the ERBB receptor
      family, is located at 8p12-p22, in or close to a region frequently amplified in
      breast carcinoma. Amplification of HGL was detected in three of 83 (3.6%) cases
      of breast tumors. No overexpression of the gene was observed in the amplified
      tumors. This and the low incidence of amplification suggest that HGL is not the
      key gene of the 8p12 amplification but may be used as a marker of large
      amplification units.

PMID- 7529050
TI  - Analysis of mutations in the SCH gene in schwannomas.
AB  - Schwannomas are benign tumors of cranial, spinal, and other nerve sheaths that
      develop sporadically or are inherited as part of neurofibromatosis type 2 (NF2).
      The NF2 gene (SCH) on chromosome 22 has recently been identified and shown to be
      inactivated by mutation and allele loss in some schwannomas. However, only
      limited regions in the SCH coding region were examined for mutations. We have
      extended these studies by screening virtually all coding sequences of the SCH
      gene (95% coverage) and adjacent splice site sequences for the presence of
      mutations in 48 schwannomas. All tumors (34 vestibular schwannomas and 14
      schwannomas of other locations) were additionally characterized for allele loss
      on chromosome 22. By PCR-DGGE screening of the 16 known exons of the SCH gene, 22
      mutations were found. Most of these give rise to a premature stop codon and are
      expected to result in the synthesis of a truncated gene product (schwannomin).
      Although there was no apparent hotspot for mutations, 16 of the 22 mutations
      occurred in the first eight exons or adjacent splice site sequences of the SCH
      gene. In several vestibular as well as other schwannomas loss of one SCH allele
      and mutational inactivation of the second allele were identified in the same
      tumor. Our data indicate that the SCH gene is implicated in the development of
      schwannomas of all locations in the nervous system.

PMID- 7529051
TI  - Sequencing of cDNAs encoding alpha 1-microglobulin/bikunin of Mongolian gerbil
      and Syrian golden hamster in comparison with man and other species.
AB  - Complementary DNAs (cDNAs) encoding alpha 1-microglobulin (alpha 1mG)/bikunin,
      also known as inter-alpha-inhibitor (I alpha I) light chain, were cloned from
      liver extracts of the Mongolian gerbil, Meriones unguiculatus, and the Syrian
      golden hamster, Mesocricetus auratus, by reverse transcription-polymerase chain
      reaction and rapid amplification of cDNA ends methods. From the deduced amino
      acid sequences of alpha 1mG/bikunin of gerbil and hamster, the basic molecular
      structure of the proteins seemed to be well-conserved. However, near the proposed
      sequence of proteinase inhibitory sites of two Kunitz domains in the bikunin
      part, variable regions composed of three amino acids each were observed between
      species, including rodents. Since the second half of bikunin is genetically
      identical with the mast cell proteinase inhibitor, trypstatin, the bikunin of
      each animal may have distinct inhibitory activity against mast cell proteinases.

PMID- 7529052
TI  - [Treatment with a combination of G-CSF and ganciclovir in a patient with
      retinitis caused by cytomegalovirus and AIDS].

PMID- 7529053
TI  - Identification of limulin as a major cytolytic protein in the plasma of the
      American horseshoe crab, Limulus polyphemus.

PMID- 7529054
TI  - Clearance of proteases from the circulation of the American horseshoe crab,
      Limulus polyphemus: a possible function for alpha2-macroglobulin.

PMID- 7529055
TI  - Ionic fluxes during wound healing following segment amputation in sabellid
      fanworms.

PMID- 7529056
TI  - Three-dimensional calibration of the non-invasive ion probe, NVP(i), of steady
      ionic currents.

PMID- 7529057
TI  - [Antithrombotic therapy in patients with chronic atrial fibrillation].

PMID- 7529058
TI  - Ising model for cooperative processing of extracellular information by protein
      tyrosine kinases and cell adhesion molecules.
AB  - Activation of receptor tyrosine kinases by multiple growth (GFs) is a major
      process through which mitogenic information is transmitted into cells. Cell cycle
      progression additionally requires the coordinated interaction of cellular
      adhesion receptors with extracellular matrix (ECM) molecules. Recent data from
      several groups, which demonstrated that integrin-ECM contacts promote multiple
      phosphorylations of intracellular components although the integrin cytoplasmic
      domains do not have intrinsic protein kinase activity, support the theory that
      some adhesion receptor families transduce extracellular signals cooperatively
      with protein-tyrosine kinases (PTKs). Based on the well-established hypothesis
      that adhesion receptors induce an aggregation of PTKs through a rearrangement of
      the cytoskeleton, a mathematical minimal model for the regulation of PTKs is
      presented which accounts for the synergism between different environmental
      signals mediated by growth factors and cell adhesion molecules (CAM) or cell
      adhesion associated substances like carcinoembyronic antigen (CEA). The model,
      which is closely related to a two-dimensional Ising model describing order
      disorder transitions in ferromagnetic crystals, provides evidence that a cell
      type-specific pattern of cell adhesion molecules may function as a molecular
      amplifier which promotes the metastatic activity of malignant tumor cells through
      the indirect induction of intracellular PTK activity.

PMID- 7529059
TI  - Erythrocyte blood group antigens: not so simple after all.

PMID- 7529060
TI  - Enrichment of human hematopoietic stem cell activity in the CD34+Thy-1+Lin-
      subpopulation from mobilized peripheral blood.
AB  - The number of CD34+ cells in the peripheral blood of cancer patients is known to
      be increased following the administration of high dose chemotherapy and
      hematopoietic growth factors. These so-called peripheral blood stem cell grafts
      are now frequently used for autologous transplantation of patients with
      malignancies. In this report, we address the question of whether true long-term
      repopulating pluripotent hematopoietic stem cells (PHSC) are mobilized into
      peripheral blood following chemotherapy plus granulocyte/macrophage colony
      stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF)
      mobilization. We have examined the presence of stem cells in mobilized peripheral
      blood (MPB) by using an antibody to the human Thy-1 molecule to stain the
      CD34+Lineage- (Lin-) population. The kinetics of mobilization of CD34+Thy-1+ Lin-
      cells into peripheral blood were studied, and the percentage of cells with this
      phenotype was found to vary widely depending on the day of leukapheresis. A
      CD34+Thy-1+Lin- cell population, potentially containing PHSCs, was isolated by
      fluorescence activated cell sorting (FACS) and analyzed for activity. The
      multilineage differentiative capacity of this candidate stem cell-containing
      population in MPB was determined using an in vitro long-term culture system, in
      which cobblestone area formation was used as a means of detecting PHSCs. We also
      measured repopulating capacity by using two in vivo models in which severe
      combined immunodeficiency (SCID)-hu mice were implanted with human fetal bone or
      thymus grafts. Using these assays, we show that the highest frequency of
      cobblestone area-forming cells (CAFC) after 7 weeks of culture was observed in a
      subpopulation of CD34+Lin- cells, which expressed low levels of Thy-1. This cell
      population was capable of producing both B and myeloid cells, and maintaining
      CD34+Lin- cells in these long term cultures. Moreover, the CD34+Thy-1+Lin- cell
      subset possessed a higher ability to engraft and to demonstrate multilineage
      differentiative potential at 8 weeks in the SCID-hu bone assay. However, in the
      SCID-hu thymus model, both Thy-1+ and Thy-1- subpopulations were capable of donor
      T-cell engraftment at 6 weeks, suggesting the presence of cells capable of
      initiating T lymphopoiesis in both populations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7529062
TI  - Platelets generated in vitro from proplatelet-displaying human megakaryocytes are
      functional.
AB  - An in vitro culture system demonstrating the transitions from megakaryocyte
      progenitors to functional platelets is described. CD34-selected cells from normal
      human peripheral blood are cultured under conditions that promote megakaryocyte
      formation. After 8 to 11 days, enriched populations of mature megakaryocytes are
      replated under conditions that favor the development of proplatelets.
      Proplatelets express the platelet-specific proteins, glycoproteins Ib and IIb
      (GPIb and GPIIb), and fibrinogen and also contain microtubule coils equal in size
      to those found in plasma-derived platelets. In addition, proplatelets have
      ultrastructural features in common with plasma-derived platelets. Platelet-sized
      particles from the proplatelet culture supernatants are examined.
      Ultrastructurally, these particles are identical to plasma-derived platelets.
      Functionally, these culture-derived platelets aggregate in response to both
      thrombin and adenosine diphosphate (ADP) plus fibrinogen. This aggregation is
      specifically inhibited by the addition of a function-blocking anti-GPIIbIIIa
      antibody. Culture-derived platelets stimulated with agonists also express the
      activation-dependent antigens P-selectin and functional fibrinogen receptor. This
      is the first description of an in vitro culture system that sequentially
      demonstrates megakaryocyte growth, development, and platelet production.

PMID- 7529061
TI  - The Mpl receptor is expressed in the megakaryocytic lineage from late progenitors
      to platelets.
AB  - The Mpl receptor (Mpl-R) is a cytokine receptor belonging to the hematopoietin
      receptor superfamily for which a ligand has been recently characterized. To study
      the lineage distribution of Mpl-R in normal hematopoietic cells, we developed a
      monoclonal antibody (designated M1 MoAb) by immunizing mice with a soluble form
      of the human Mpl-R protein. With few exceptions, Mpl-R was detected by indirect
      immunofluorescent analysis on all human leukemic hematopoietic cell lines with
      pluripotential and megakaryocytic phenotypes, but not on other cell lines. By
      immunoprecipitation and immunoblotting, M1 MoAb recognized a band at 82 to 84 kD
      corresponding to the expected size of the glycosylated receptor. Among normal
      hematopoietic cells, M1 MoAb strongly stained megakaryocytes (MK) and Mpl-R was
      detected on platelets by indirect immunofluorescence staining or immunoblotting.
      On purified CD34+ cells, less than 2% of the population was stained, but the
      labeling was weak and just above the threshold of detection. However, dual
      labeling with the M1 and antiplatelet glycoprotein MoAbs showed that most Mpl
      R+/CD34+ cells coexpressed CD41a, CD61, or CD42a, suggesting that cell surface
      appearance of Mpl-R and platelet glycoproteins could be coordinated. M1-positive
      and M1-negative subsets were sorted from purified CD34+ cell populations. Colony
      assays showed that the absolute number of hematopoietic progenitors was extremely
      low and no primitive progenitors were present in the CD34+/Mpl-R+ fraction.
      However, this cell fraction was significantly enriched in low proliferative
      colony-forming units-MK. When the CD34+/Mpl-R+ fraction was grown in liquid
      culture containing human aplastic serum and a combination of growth factors,
      mature MK were seen as early as day 4, whereas the predominant cell population
      was erythroblasts on day 8. Similar data were also obtained with the CD34+/Mpl-R-
      fraction with, however, a delay in the time of appearance of both MK and
      erythroblasts. In conclusion, Mpl-R is a cytokine receptor restricted to the MK
      cell lineage. Its expression is low on CD34+ cells and these cells mainly
      correspond to late MK progenitors and transitional cells. These data indicate
      that the action of the Mpl-R ligand might predominate during the late stages of
      human MK differentiation.

PMID- 7529063
TI  - Glanzmann's thrombasthenia associated with deletion-insertion and alternative
      splicing in the glycoprotein IIb gene.
AB  - Glanzmann's thrombasthenia is a bleeding disorder characterized by a decrease or
      absence of the functional platelet membrane glycoprotein (GP) complex, GPIIb/IIIa
      (alpha IIb beta 3). We describe a new deletion-insertion mutation in the GPIIb
      gene causing type I Glanzmann's thrombasthenia in two siblings of a
      consanguineous Iranian-Jewish family. The proband's platelets bound more
      antibodies against the vitronectin receptor-alpha V beta 3 than normal platelets,
      suggesting a normal GPIIIa (beta 3) gene and a defect in the GPIIb gene.
      Sequencing of amplified cDNA and genomic DNA fragments showed a 6-bp deletion and
      31-bp insertion in exon 25 of the GPIIb gene. The predominant platelet GPIIb mRNA
      of the proband was a product of the splicing of exon 24 to a cryptic AG acceptor
      site in the insertion and encoded for deletion of amino acids Leu817-Asn826 and
      insertion of eight different amino acids. Cotransfection of COS-7 cells with
      expression vectors containing wild-type GPIIIa cDNA and the mutated GPIIb cDNA
      failed to produce detectable amounts of GPIIb/IIIa on the surface of the cells.
      Allele-specific restriction analysis of genomic DNA of family members showed
      homozygosity for the mutation in the affected siblings, heterozygosity in the
      parents, and homozygosity for the normal allele in an unaffected sibling. The
      observed mutation is in a region that is conserved from rodents to humans and has
      been suggested to be involved in the interaction between GPIIb and GPIIIa when
      these GPs are complexed in solution.

PMID- 7529064
TI  - In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+
      peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain.
AB  - Multiple myeloma (MM) is characterized by a plasma cell infiltrate of the bone
      marrow (BM). However, late-stage monotypic B cells have been detected in the
      blood. This work analyzes the effects of clinical treatment on late stage CD19+ B
      cells present in 752 blood samples from 152 MM patients. MM patients have 2 to 8
      times as many circulating CD19+ cells as do normal donors. Analysis of the Ig
      heavy chain (IgH) gene rearrangements using polymerase chain reaction indicates
      that the CD19+ population includes cells sharing the same clonotypic CDR3 region
      as is detected in the BM plasma cells, for patients analyzed during chemotherapy
      or in relapse. They are also monotypic as defined by their cytoplasmic or surface
      expression of Ig kappa or lambda light chain. The light chain restriction is the
      same as that of the BM plasma cells. Individual patients observed over 1- to 2
      year periods exhibit considerable variation in the number of B cells present in
      blood; this number does not correlate with the concentration of serum monoclonal
      Ig. The monoclonal blood CD19+ cells are not eliminated by any of the
      chemotherapy regimens analyzed and remain at high levels during transient
      remissions. Patients in the progressive phase of disease or in relapse have
      significantly higher numbers of B cells than do patients in transient remission
      or untreated patients. During periods when the quantity of blood B cells
      approaches normal, phenotypically their quality is highly abnormal, with physical
      and phenotypic heterogeneity. Most B cells express CD45R0, a high density of
      CD38, and CD56 characteristic of late-stage B or pre-plasma cells. CD38hi blood B
      cells had a cyclical presence. We conclude that monoclonal B cells in the blood
      of myeloma patient populations include drug-resistant reservoirs of clonotypic
      cells that may underlie relapse.

PMID- 7529065
TI  - Ex vivo expansion and selection of human CD34+ peripheral blood progenitor cells
      after introduction of a mutated dihydrofolate reductase cDNA via retroviral gene
      transfer.
AB  - Retroviral gene transfer into human myeloid precursor cells allows introduction
      of marker genes as well as genes conferring resistance to chemotherapeutic drugs.
      We transduced a human mutant dihydrofolate reductase (DHFR) cDNA into CD34
      antigen-positive peripheral blood cells from patients with breast or ovarian
      cancer obtained after treatment with chemotherapy and granulocyte colony
      stimulating factor (G-CSF). This mutant DHFR has been shown to confer resistance
      to methotrexate (MTX) in murine bone marrow. We established a transduction
      protocol that permitted ex vivo expansion and selection of transduced early
      progenitor cells. The number of progenitor cells from transduced CD34-positive
      cells increased 50-fold after cytokine prestimulation with interleukin-1 (IL-1),
      c-kit ligand (KL; stem cell factor), and IL-3 and 2 weeks in liquid culture.
      Transduced colony-forming unit-granulocyte-macrophage (CFU-GM), assayed directly
      after the transduction procedure, were protected completely against 2 x 10(-8)
      mol/L MTX, a concentration that significantly reduced the CFU-GM detected in the
      control population. Gene transfer of the mutant DHFR led to a twofold selective
      advantage for a pre-CFU population after exposure to MTX in liquid culture (P <
      .001). Polybrene, in contrast with protamine, significantly inhibited the
      expansion of progenitors. The presence of proviral DNA was monitored by
      polymerase chain reaction (PCR) and was detected in greater than 80% of CFU-GM
      and ex vivo expanded pre-CFU. We have demonstrated that human hematopoietic
      precursor cells can be expanded extensively after retroviral gene transfer. The
      same population of early progenitors can be selected ex vivo with low-dose MTX.
      As long-term expression of transduced genes in human hematopoietic cells remains
      a problem in vivo, these results may have implications for future clinical
      trials, especially for the introduction of nonselectable genes.

PMID- 7529066
TI  - Peripheral blood stem cell transplants for multiple myeloma: identification of
      favorable variables for rapid engraftment in 225 patients.
AB  - Transfusion of autologous peripheral blood stem cells (PBSCs) of good quality
      ensures fast hematopoietic engraftment after myeloablative therapy with a
      decrease in procedure-related morbidity and mortality. We have analyzed variables
      influencing the kinetics of engraftment, and therefore reflecting the quality of
      PBSC collections, in 225 patients with newly diagnosed or refractory multiple
      myeloma (MM) who received an autotransplant in support of high dose melphalan
      (200 mg/m2); 132 of these patients also completed a second transplant. All PBSCs
      were collected before the first transplant after high-dose cyclophosphamide (6
      g/m2) and hematopoietic growth factors, mainly granulocyte-macrophage colony
      stimulating factor. PBSCs were administered either alone (91 patients) or with
      bone marrow (134 patients). A highly significant correlation was observed between
      the number of CD34+ cells per kilogram infused and prompt recovery of both
      granulocytes (P = .0001) and platelets (P = .0001). After correction for the
      proportion of patients with > or = 2 x 10(6)/kg CD34 PBSCs infused and with < or
      = 12 months of prior therapy, no difference in engraftment kinetics was seen
      between patients receiving PBSCs only and those also receiving bone marrow.
      Exposure to chemotherapy, even to < or = 6 months of alkylating agents,
      significantly delayed hematopoietic recovery posttransplantation. The threshold
      dose of CD34 cells necessary for prompt engraftment was > or = 2.0 x 10(6)/kg for
      patients with < or = 24 months of chemotherapy before the first transplant,
      whereas greater than 5 x 10(6)/kg CD34 cells were required to assure rapid
      recovery also in those with longer exposure. Such quantities, easily collected in
      the large majority of patients with shorter exposure (91%), were obtained in only
      28% of patients with more than 24 months of prior chemotherapy. Rapid platelet
      recovery within a narrow range of time (before day 14) was almost invariably seen
      (94%) when greater than 5 x 10(6)/kg CD34 cells were infused, irrespective of the
      duration of prior therapy, whereas the range widened progressively when less CD34
      cells were infused. In the absence of CD34 measurements, fast recovery of
      platelets to greater than 50 x 10(9)/L within 14 days after high-dose
      cyclophosphamide and < or = 12 months of prior chemotherapy were the best
      predictors of early engraftment. Prudent use of stem cell-damaging agents, such
      as melphalan and nitrosoureas, is recommended in MM patients who might be
      candidates for autotransplantation. Alternatively, PBSCs should be collected
      early after diagnosis.

PMID- 7529067
TI  - 5-fluorouracil modulation in the chemotherapy of colorectal cancer.
AB  - More than ten years after the introduction into the clinic of Folinic Acid
      associated with 5-FU in the treatment of colorectal cancer, it appears that in
      terms of objective responses, associations with modulating agents are more
      effective than 5-FU alone. An improvement in survival has been observed in some
      studies, but this remains a debated subject. Results can probably be further
      improved by multiple modulation also using Interferon and by a more careful
      evaluation of drug scheduling. The data on the activity of modulated 5-FU in the
      adjuvant treatment of colon cancer await the publication of confirmatory trials,
      but they are already sufficiently convincing to assert that adjuvant treatment
      should be part of the standard approach to patients with locally advanced colon
      carcinoma. The comparison of reports from different groups emphasizes the need
      for protocol standardization and a better description of patients based not only
      on pathological staging, but also on the biological characteristics of the
      tumour.

PMID- 7529068
TI  - Plasticity of postganglionic sympathetic neurons in the rat superior cervical
      ganglion after axotomy.
AB  - The neuropeptides galanin (GAL) and vasoactive intestinal polypeptide (VIP) are
      upregulated in spinal and vagal sensory as well as in cranial motor neurons after
      axonal transection. In this study an increase of both peptides is demonstrated in
      axotomized principal ganglionic neurons (PGN) of the rat sympathetic superior
      cervical ganglion by use of double-labeling immunofluorescence. Compared to
      control ganglia that do not contain more than 1% GAL- or VIP-positive cells,
      about 26% of all PGN exhibit GAL immunoreactivity by day 1 after transection of
      the major postganglionic branches. The proportion of immunoreactive neurons
      reaches its maximum after 30 days (40%) and decreases to about 27% within the
      second month after axotomy. The percentage of VIP-positive neurons is much lower
      than for GAL: 2% of the PGN exhibit VIP immunoreactivity at day 1 and about 7%
      are observed 30 and 60 days after axotomy. In order to further characterize newly
      GAL- and VIP-positive PGN, their cell diameters were determined 12 days after
      axotomy. Compared to the mean overall neuron diameter of 24.8 microns, GAL
      immunoreactive neurons are predominantly of small and intermediate size (22.2
      microns), whereas VIP occurs mainly in larger neurons (26.1 microns). Besides
      cell bodies, many intraganglionic nerve fibers stain positive for GAL or VIP,
      particularly at day 6. Most likely, these fibers represent axons, as indicated by
      the absence of MAP2, a cytoskeletal protein found in neuronal somata and
      dendrites. They establish direct membrane contacts with postganglionic perikarya,
      as revealed by pre-embedding immuno-electron microscopy. Some cell bodies and
      fibers contain both peptides. Colocalization of GAL or VIP with tyrosine
      hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis, reveals a
      reduced immunoreactivity for TH in intensely GAL- or VIP-positive cells, and vice
      versa at day 6. However, no difference in staining intensity for VIP or GAL, and
      TH, is observed after 30 and 60 days. Possible implications of GAL and VIP for
      peripheral nerve regeneration and their regulation by target-derived factors are
      discussed.

PMID- 7529069
TI  - Immunohistochemical demonstration of galanin-, and galanin message-associated
      peptide-like immunoreactivities in sympathetic ganglia and adrenal gland of the
      guinea pig.
AB  - Using the indirect immunofluorescence method, the distribution of galanin (GAL)-
      and galanin message-associated peptide (GMAP)-like immunoreactivities (LI) were
      studied in sympathetic ganglia and the adrenal gland of the guinea pig. A rather
      dense network of GAL-immunoreactive nerve fibers was found in the inferior
      mesenteric ganglion (IMG) and in the superior mesenteric pole of the celiac
      superior mesenteric ganglion complex (C-SMG). The celiac pole of the C-SMG, the
      stellate ganglion, and the superior cervical ganglion contained fewer, mostly
      scattered fibers. SIF-cells in prevertebral and paravertebral ganglia contained
      GAL-LI, as did the adrenal medullary cells. The GAL fibers in the IMG surrounded
      mainly principal ganglion cells containing somatostatin-immunoreactivity (SOM
      IR), whereas fewer fibers were seen around neuropeptide Y (NPY) cells and cells
      in which SOM and NPY coexisted. Application of colchicine or vinblastine onto the
      IMG did not result in the appearance of GAL-IR in the principal ganglion cells.
      In denervation experiments it was revealed that most of the GAL fibers reach the
      IMG via the lumbar splanchnic nerves. GAL-IR appears to be colocalized with
      substance P (SP) in fibers of the IMG, indicating an origin of the GAL-containing
      fibers in dorsal root ganglia (DRG). This conclusion was supported by the finding
      in lumbar DRGs of GAL-positive cell bodies that contained SP. The role of GAL in
      prevertebral ganglia is unclear. It may be suggested that GAL modulates the slow,
      long-lasting membrane depolarization of the principal ganglion cells caused by SP
      in the primary afferents related to the IMG. GMAP-LI was detected in SIF cells
      and adrenal medullary cells in which GMAP-LI parallels the immunoreactivity of
      GAL. GMAP-LI was not observed in neuronal cell bodies or nerve fibers of the
      ganglia.

PMID- 7529072
TI  - Nitric oxide synthase-containing neurons in the pig large intestine: topography,
      morphology, and viscerofugal projections.
AB  - The distribution of neurons that are capable of synthesizing nitric oxide (NO)
      has been demonstrated in the porcine large intestine by means of NO synthase
      (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPHd) histochemistry. An overall colocalization of NOS
      immunoreactivity and NADPHd staining was observed. Nitrergic neurons were
      abundant in the myenteric and outer submucous plexus of the caecum, colon, and
      rectum. Only a few nitrergic perikarya were seen in the inner submucous plexus of
      the colon and caecum, whereas a substantially larger number was observed in the
      rectum. Nitrergic nerve fibers were present in the three ganglionic nerve
      plexuses. Contrary to the outer longitudinal muscle layer and the mucosal region,
      the circular muscle layer received a dense nitrergic innervation. The nitrergic
      nerve cells were variable in size and shape, and several displayed vasoactive
      intestinal polypeptide (VIP) immunoreactivity (IR). Retrograde tracing studies
      revealed the existence of nitrergic neurons that project to the caudal (inferior)
      mesenteric ganglion. They were observed in the myenteric and outer submucous
      plexus of the transverse and descending colon and the rectum. These observations
      strongly suggest that several subpopulations of NO-synthesizing neurons, namely,
      motor neurons and interneurons, should be distinguished in the porcine large
      intestine, thereby emphasizing the importance of NO as a biologically active
      mediator.

PMID- 7529070
TI  - Nitric oxide modulates sympathetic neurotransmission at the prejunctional level.
AB  - In spite of accumulating evidence for a modulation of sympathetic
      neurotransmission by endogenously produced nitric oxide (NO), it remains unclear
      in which parts of the vascular system and at what level this interaction takes
      place. The aim of the present study was to investigate the distribution of
      endothelial and neuronal NO synthase (NOS) along the vascular tree of the heart
      at the light and electron microscopic level using NADPH-diaphorase (NADPH-d)
      staining as a marker for NOS. In addition, the functional effects of exogenous NO
      on coronary vascular resistance and cardiac adrenergic nerves was studied using
      the isolated perfused rat heart as a model. The intraaxonal catecholamine content
      of adrenergic nerve fibers was visualised and morphometrically assessed by
      applying glyoxylic acid-induced histofluorescence. The expression of endothelial
      NOS in the heart was found to depend on the diameter of the blood vessel.
      Arteries > 100 microns always showed intense staining, whereas staining in
      smaller arteries and veins was considerably weaker. Smooth-muscle free vessels
      were essentially devoid of NADPH-d activity. In atrial and ventricular
      myocardium, neuronal NOS localised in autonomic nerve fibers along the entire
      vascular tree. Ultrastructurally, NADPH-d staining revealed adjacent localisation
      of NOS-positive and -negative axons, suggesting and interaxonal modulation of
      adjacent autonomic nerve fibers by NO. In isolated perfused rat hearts, the
      intracoronary application of 10(-8) M NO produced a marked decrease of coronary
      perfusion pressure, which was accompanied by a distinct increase in intraaxonal
      catecholamine levels of intramural adrenergic nerve fibers.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7529071
TI  - Synaptic morphology of substance P terminals on catecholamine neurons in the
      commissural subnucleus of the nucleus tractus solitarii in the rat.
AB  - The ultrastructure of substance P-containing nerve terminals synapsing on
      catecholamine neurons in the rat commissural subnucleus of the nucleus tractus
      solitarii (NTScom) was studied using a double immunocytochemical labeling
      technique. Although there were numerous tyrosine hydroxylase-immunoreactive (TH
      I) somata present, substance P immunoreactive (SP-I) cell bodies were only
      occasionally found in the NTScom. At the light microscopic level, many SP-I
      terminals were seen closely associated with TH-I dendrites and somata. At the
      electron microscopic level, SP-I terminals synapsing on TH-I structures were also
      readily encountered. SP-I terminals contained small, clear, and predominantly
      spherical vesicles (32 +/- 4 nm diameter), as well as large dense-cored vesicles
      approximately 100 nm in diameter. Postsynaptic TH-I dendritic profiles of various
      calibers and somata were encountered. These postsynaptic TH-I structures often
      showed postsynaptic densities. The morphological features of the SP-TH synapses
      in the present study, that is, the size of synaptic vesicles and the presence of
      postsynaptic densities, are quite different from those of central carotid sinus
      afferent synapses reported in our previous study [Chen et al. (1992), J.
      Neurocytol., 21:137-147]. Therefore, most of the SP terminals of the SP-TH
      synapses in the NTScom appear not to originate from the carotid sinus afferents.
      SP-I second-order neurons of the carotid sinus afferent pathway [Chen et al.
      (1991), J. Auton. Nerv. Syst., 33:97-98] may be one of the possible sources of
      such terminals.

PMID- 7529074
TI  - Nitric oxide synthase containing neurons in the carotid body and sinus of the
      guinea pig.
AB  - The morphology and function of the carotid sinus and carotid body have been
      extensively studied, but our knowledge of their transmitter(s) is still
      incomplete. Nitric oxide (NO) recently has been identified as a novel messenger
      molecule in a number of neuronal and non-neuronal tissues. Nitric oxide synthase
      (NOS) has been demonstrated in many neurons of the autonomic nervous system. The
      present study examines the distribution of NOS in the carotid sinus and body. The
      carotid sinus and body of newborn guinea pigs were removed for histochemical
      examination of NOS using the NADPH-diaphorase method. In the carotid body, many
      nerve fibers enveloping the glomus cells were positive for NOS. In addition, some
      glomus cells were positive for NOS. In the carotid sinus, NADPH-d positive fibers
      were distributed unevenly in the adventitia and media. These results indicate the
      possibility that nitric oxide plays a role in both arterial chemoreception and
      baroreception.

PMID- 7529076
TI  - RHAMM, a receptor for hyaluronan-mediated motility, on normal human lymphocytes,
      thymocytes and malignant B cells: a mediator in B cell malignancy?
AB  - RHAMM (Receptor for HA Mediated Motility) is a novel HA receptor that has been
      linked to regulating cell locomotion and density dependent contact inhibition of
      fibroblasts, smooth muscle cells, macrophages, lymphocytes, astrocytes and sperm.
      The ubiquitous expression of RHAMM suggests the existence of multiple isoforms,
      and indeed, RHAMM is found in various cellular compartments, namely nuclear,
      cytosolic, membrane-bound and extracellular. In this review, we emphasize the
      evolving role of RHAMM in B cell malignancies, and examine the function of RHAMM
      in T cell development in the thymic microenvironment. Both the motile behaviour
      of progenitor thymocytes (CD3-CD4-CD8-) and malignant B cells from multiple
      myeloma (MM), plasma cell leukemia, and hairy cell leukemia was blocked by
      monoclonal antibodies to RHAMM, suggesting that motility may correlate with
      increased expression of RHAMM at the cell surface. Interestingly, the soluble
      form of RHAMM is able to inhibit fibroblast locomotion, and it is likely that a
      balance between expression of both forms determines, in part the motility of
      cells. RHAMM appears to play a fundamental role in the immune system and the
      ability of RHAMM to function as a motility receptor is likely to be due to
      complex variables including the extent to which soluble RHAMM is secreted. RHAMM
      expression characterizes circulating monoclonal B cells as abnormal. potentially
      invasive and/or metastatic components of myeloma and may underlie the malignant
      behavior of these cells.

PMID- 7529075
TI  - Expression of E-selectin, ICAM-1 and VCAM-1 on bronchial biopsies from allergic
      and non-allergic asthmatic patients.
AB  - The bronchial mucosa of asthmatic patients is characterized by a large influx of
      eosinophils, monocytes and lymphocytes. Leucocyte migration and accumulation is
      thought to involve adhesion molecules, as shown in an animal of allergic asthma
      and in humans with other allergic diseases. The aim of this study was to evaluate
      the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and
      vascular cellular adhesion molecule-1 (VCAM-1) on endothelium and epithelium in
      bronchial biopsies obtained from patients with allergic (n = 17) and non-allergic
      asthma (n = 18). Bronchial biopsies were taken in asthmatic patients and control
      subjects (n = 10) by fiberoptic bronchoscopy and embedded in paraffin. The
      cellular infiltrate was evaluated by May-Grunwald-Giemsa staining. Adhesion
      molecule expression was analyzed by immunohistochemistry using mouse monoclonal
      antibodies; the results were expressed as the percentage of positive cells. For
      each patient, we evaluated the severity of asthma as defined by the AAS score and
      the treatment. In controls, low expression of ICAM-1 was observed on the
      epithelium and endothelium (9.6 +/- 2.7 and 11.2 +/- 4.1%, respectively), while E
      selectin and VCAM-1 were not expressed. In patients with allergic asthma, a
      significant increase of ICAM-1 expression was observed on epithelium and
      endothelium (28 +/- 5.3 and 35.6 +/- 5%, respectively), whereas E-selectin (17.4
      +/- 4.8%) and VCAM-1 (12.8 +/- 3.6%) were overexpressed only on endothelium. In
      allergic asthmatic patients, adhesion molecule expression on endothelium was
      correlated with eosinophil and total leucocyte infiltrate (p < 0.05). In
      contrast, adhesion molecule expression in biopsies from patients with non
      allergic asthma (14.1 +/- 5.2 and 15.3 +/- 3.6% for ICAM-1 expression on
      epithelium and endothelium, respectively) was not significantly different from
      the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529078
TI  - Detection of trisomy 12 by FISH in untreated B-chronic lymphocytic leukemia:
      correlation with stage and CD20 antigen expression intensity.
AB  - We studied cells from 30 controls and 85 cases of untreated B-chronic lymphocytic
      leukemia (CLL) with a fluorescence in-situ hybridization (FISH) technique
      utilizing a probe to chromosome 12. By use of a threshold of > 2% for trisomy 12
      for the CLL cases (the mean +3 SD for controls was 1.3%), 20% (17/85) were
      trisomy 12. The mean % cells positive was 32.6 (median, 39.4; range, 2.4-79.1).
      There was a trend toward an higher incidence of trisomy 12 in patients with Rai
      stages 1-4 vs Rai 0 (p = 0.16). Forty-seven % (8/17) of patients with trisomy 12
      had strong intensity CD20 antigen expression compared to 21% (14/68) of patients
      without trisomy 12 (p = 0.03). Trisomy 12 associated with CLL is easily detected
      by FISH with an overall incidence of 20%. This technique should be applied to
      larger groups of patients to confirm the potential variation among Rai stages and
      immunophenotypic subgroups.

PMID- 7529077
TI  - The c-kit molecule and the surface immunophenotype of human acute leukemia.
AB  - The proto-oncogene c-kit encodes the receptor for a stem cell factor (c-kit
      molecule). Expression of the c-kit molecule on the gated leukemic blast cells
      from newly diagnosed patients with leukemia was analysed by flow cytometry using
      the monoclonal antibody (17F11). Among 35 myeloid leukemia cases examined,
      significant c-kit-positive blast cells were detected in 24 cases (69%), even
      though the percentage of positive cells was widely variable. The correlation
      between the percentage of cells positive for the c-kit molecule and the
      percentage of cells positive for CD34 was found to be statistically significant
      (rs = 0.36, p < 0.05). Fifteen cases of myeloid leukemia were positive for
      lymphoid markers. The mean percentage of the cells expressing c-kit molecule
      among the lymphoid marker-positive cases was significantly larger than that among
      the lymphoid marker-negative cases (p < 0.05). All 19 lymphoid leukemia cases
      were c-kit-negative, including 8 cases which were positive for some myeloid
      markers. Stem cell factor enhanced the colony growth in five out of six acute
      myeloblastic leukemia cases expressing the c-kit molecule. On the other hand, SCF
      did not stimulate colony growth in any of the four cases which were not positive
      for the c-kit molecule. These findings indicated that the distribution of flow
      cytometrically detectable c-kit molecules on leukemic cells is related to the
      morphologic and immunologic classification of these leukemic cells and to the
      expression of the CD34 cell surface molecule on some myeloid leukemic cells. On
      such cells, expression of the c-kit molecule may have a functional role and be
      related to the maturation process.

PMID- 7529073
TI  - Neuroepithelial endocrine and nervous system in the respiratory tract of Cynops
      pyrrhogaster with special reference to the distribution of nitric oxide synthase
      and serotonin.
AB  - The respiratory tract of urodeles harbours an intramural nerve network comprising
      an innervated system of neuroepithelial endocrine (NEE) cells. However, striking
      differences have been noted between phylogenetically closely related species.
      Zamboni- or formaldehyde-fixed whole-mount preparations and sections of the
      saclike lungs of a Japanese salamander, Cynops salamander, Cynops pyrrhogaster,
      have been investigated for the immunocytochemical detection of nitric oxide
      synthase (NOS), serotonin (5-HT), VIP, somatostatin, calcitonin, and bombesin;
      for the enzyme-cytochemical demonstration of NADPH diaphorase (NADPHd); and for
      formaldehyde-induced fluorescence. In addition, the ultrastructural morphology
      has been examined by using glutaraldehyde/osmium tetroxide fixed lung tissues.
      Ovoid 5-HT-immunoreactive (IR) NEE cells occur singly or grouped in the
      ciliomucous epithelium of the trachea and lungs of Cynops, and a few somatostatin
      , calcitonin-, and bombesin-like IR NEE cells are also observed. These cells
      exhibit a characteristic neuroendocrine morphology as seen with the electron
      microscope. In addition, large numbers of 5-HT-IR interstitial cells, with round
      to oval cell bodies and two or three long, slender, sometimes branching
      processes, are located preferentially along large blood vessels in the connective
      tissue capsule of the lung and trachea. Immunoelectronmicroscopy shows that 5-HT
      is localized over large dense granules in the cell bodies and processes of these
      interstitial cells. NOS-like immunoreactivity occurs in a nerve plexus composed
      of thick nerve bundles and nerve cells, and in a fine varicose nerve network that
      originates at least partly from intrapulmonary NOS-containing nerve cells. VIP
      like immunoreactivity appears to be colocalized with NOS in the latter network.
      All NOS-positive nerve fibres in the lungs of Cynops pyrrhogaster and Ambystoma
      mexicanum stain for NADPHd. It is concluded that the pulmonary NEE cells observed
      in Cynops pyrrhogaster are similar to those described in other vertebrate species
      and that the 5-HT-IR interstitial cells resemble mast cells. In addition, nitric
      oxide is likely to be a bioactive substance involved in nonadrenergic,
      noncholinergic inhibitory neurotransmission in the pulmonary nervous system of
      urodeles, where it may be colocalized with VIP.

PMID- 7529079
TI  - Functional expression of a mouse growth hormone receptor cDNA in transfected
      mouse L cells.
AB  - A cDNA encoding a full-length mouse (m) growth hormone receptor (GHR) derived
      from 3T3 F442A cells was amplified by RT-PCR and cloned into a mammalian
      expression vector. A mouse L cell line (mGHR1.6), which expresses high levels of
      full-length mGHR, was established. A mGHR-specific mRNA of approx 2.8 kb was
      found in these cells. Ligand binding studies showed that mGHR 1.6 cells were
      capable of binding 125I-hGH with a dissociation constant (Kd) of 2.9 +/- 0.13 nM.
      Scatchard analysis indicated that mGHR1.6 cells had only a single class of mGHR
      and possessed approx 128,000 GH specific binding sites per cell. Affinity
      crosslinking studies showed that the recombinant mGHR possessed an apparent
      molecular mass of 105 kDa. In addition, mGHR1.6 cells responded to growth
      hormones (GHs) from several species. Two proteins, pp92 and pp95, were found to
      be tyrosyl phosphorylated following GH treatment. An hGH antagonist, hGH-G120R,
      inhibited GH-induced phosphorylation of both pp92 and pp95 in a dose-dependent
      manner. This cell line may be used as an in vitro model in the studies of GH
      signal transduction and in the screening of GH analogs for biological activity.

PMID- 7529081
TI  - Changes of blood CD16/CD56 (NK) and HLA-DR/CD3-positive lymphocyte amounts in HIV
      infected children, as related to clinical progression and p24-antigen/p24
      antibody presence.
AB  - This study describes a series of immunological investigations carried out on a
      group of 37 HIV-seropositive children, aged 3-4 years, in two different stages of
      disease defined according to the CDC classification; the Primary stage, an
      asymptomatic one, showing abnormal immune function (P1-Class, B-Subclass) and the
      Secondary stage, 6-8 months later, in which patients exhibited non-specific
      findings, i.e., loss of weight, persistent generalized lymphadenopathy and
      hepatosplenomegaly, associated with abnormal immune function (P2-Class, A
      Subclass). In both stages, immune function was considered 'abnormal' when
      lymphopenia and a decrease of the CD4/CD8-cell ratio were found. The phenotypes
      CD16+/56+ (NK) and HLA-DR+/CD3+ (T-activated?)-positive cells, were assessed by
      flow cytometry, and the following supplementary systemic humoral markers were
      investigated in homologus serum samples; total HIV(gp)-antibody, HIV(p24)
      antibody and p24-antigen presence. If at the primary stage, no significant
      difference from to the reference values corresponding to the age was noticed, at
      the Secondary stage the obtained data is presented separately in two subgroups,
      namely the A-subgroup characterized by the presence of total HIV(gp)-antibody,
      the presence of HIV(p24)-antibody and the absence of p24-antigenaemia, and the B
      subgroup, where total HIV(gp)-antibody was present, HIV(p24)-antibody absent and
      p24-antigenaemia present. A significant decrease of CD16+/56+ (NK)-cells was
      found within the two subgroups. As far as HLA-DR+ from CD(3+)-cells was
      concerned, only those within the B-subgroup showed a high percentage level,
      compared to the reference values. The importance of the present findings, linked
      to immune monitoring of HIV infection among children, is discussed.

PMID- 7529082
TI  - Sensitivity to bleomycin and arabinoside cytosine in lymphocytes of patients
      affected by neuroblastoma and in those of their parents.
AB  - Chromosomal instability has been described in patients affected by various
      tumors. We previously reported a high sensitivity to fragile sites induction by
      aphidicolin in lymphocytes from patients affected by neuroblastoma and in those
      from their parents. In the search for the most suitable clastogenic agent to
      enhance the possible differences between healthy controls and patients affected
      by tumors, we have now tested two other drugs: bleomycin, a radiomimetic agent
      already used in vitro on chromosomes of patients affected by other tumors and
      arabinoside cytosine, an inhibitor of DNA polymerases alfa and beta. We observed
      a high sensitivity to bleomycin both in patients and in their parents, but to
      arabinoside cytosine only in NB patients. Moreover, the two drugs induced more
      fragile sites in 1p in patients and in their parents than in healthy controls.
      This phenomenon, which we already observed after treatment with aphidicolin,
      might be related to the frequent deletions and loss of heterozigosity in 1p in
      neuroblastoma cells.

PMID- 7529080
TI  - Comparative studies on functional and secretory properties of macrophage cell
      lines derived from different anatomical sites.
AB  - In the present study, we compared four macrophage (M phi) cell lines from
      different anatomical origins for functional and secretory activities against the
      two morphogenetic forms of the fungus Candida albicans. We show that all the cell
      lines actively phagocytize the yeast and exert antimicrobial activity against
      both forms of Candida, although M phi of microglial origin are the most
      effective. When assessed for secretory properties, microglial M phi exhibit a
      peculiar pattern with respect to other M phi populations under either basal or
      stimulated conditions. In particular, only microglial M phi fail to respond to
      the hyphal form of the fungus (H-Candida), which instead acts as a potent tumor
      necrosis factor inducer in the other M phi cell lines. When exposed to H-Candida,
      microglial M phi are indistinguishable from other M phi in their ability to
      modulate specific surface adhesion molecules. In addition to strengthening the
      knowledge on functional heterogeneity among M phi, our data provide evidence on
      the peculiar behavior of microglial M phi. To what extent M phi heterogeneity may
      be related to tissue homeostasis is discussed.

PMID- 7529083
TI  - Construction and purification of domain-deleted immunoglobulin variants of the
      recombinant/chimeric B72.3 (y1) monoclonal antibody.
AB  - Chimeric antibodies have been produced against a pancarcinomic tumor associated
      antigen, TAG-72, by fusing the genes for the variable region of mouse MAb B72.3
      to the genes for the constant region of human IgG. In our efforts to optimize the
      pharmacokinetics of plasma clearance and the efficiency of tumor localization and
      penetrance of cB72.3, we have now developed truncated versions of immunoglobulin
      heavy chains. The domain-deleted antibodies are produced by transfecting cells
      that produce chimeric kappa chains with expression vectors that encode chimeric
      heavy chains lacking the sequences that encode the CH2 domain, CH3 domain, or
      both. Despite the absence of these domains, the transfectomas secrete H2L2
      tetramers with appropriate antigenic specificity. All the domain-deleted
      immunoglobulins can be purified by chromatography on Protein G Sepharose which
      binds to a site on the Fab region that is retained in the domain-deleted
      antibodies. The CH2CH3 domain-deleted immunoglobulin produced in cell culture is
      analogous in size to enzymatically produced F(ab')2.

PMID- 7529084
TI  - A commentary on the first international conference on engineered vaccines for
      cancer and AIDS; the "coming of age" of tumor immunology.

PMID- 7529087
TI  - An interview with Trudy Kenyon, R.N., staff nurse and surgical research nurse
      coordinator, Emanuel Hospital, Portland, OR.

PMID- 7529088
TI  - An interview with Cynthia R. Stahlinski, R.N., B.S.P.A., laser safety officer and
      surgical nurse.

PMID- 7529086
TI  - Leukocyte-induced angiogenesis and subcutaneous growth of B16 melanoma.
AB  - We investigated the mechanism(s) by which systemic administration of doxorubicin
      (DXR) produced growth retardation of B16 melanomas in the subcutis of syngeneic
      mice. DXR or saline was injected intravenously (i.v.) into C57BL/6 mice, and B16
      BL6 cells were implanted subcutaneously (s.c.) on day 3, 7, or 21 after DXR
      treatment. In the DXR-pretreated mice, the tumors grew at a slower rate than in
      control (saline-treated) mice. The experiments were repeated with a B16 variant
      resistant to DXR with similar results. Tumor growth retardation correlated with
      extent of myelosuppression monitored by counting bone marrow cells, circulating
      leukocytes and peritoneal macrophages. In DXR-pretreated mice reconstituted with
      1 x 10(7) viable syngeneic spleen cells, the s.c. tumors grew at a rate similar
      to that in control mice. DXR treatment and spleen cell reconstitution experiments
      were repeated in BALB/c athymic nude mice. The results were very similar. The
      growth of s.c. tumors was directly correlated with the degree of peritumoral
      vascularity. These data indicate that in addition to its well-documented direct
      antitumor effects, DXR may produce retardation of tumor growth by producing
      myelosuppression and, hence, inhibition of host cell-induced tumor angiogenesis.

PMID- 7529089
TI  - The epidemiology of measles in England and Wales: rationale for the 1994 national
      vaccination campaign.
AB  - An epidemic of between 100,000 and 200,000 cases of measles during 1995 has been
      predicted in England and Wales. This prediction was based on epidemiological
      evidence from several sources. Notifications of measles to the Office of
      Population Censuses and Surveys have risen in 1994, with a high proportion of
      cases in children aged over 10 years. An increase in the incidence of measles was
      seen in data from other sources, including laboratory reports of confirmed
      infections and consultations with general practitioners for new episodes of
      measles. Antibody tests were performed on saliva and serum from notified cases in
      several districts. Over three quarters of the notified cases in 1994 that were
      confirmed occurred in children of school age. The proportion of children aged 7
      to 14 years who were susceptible to measles, obtained from studies of the age
      specific prevalence of antibody, rose from 6.0% (146/2453) in 1986 and 1987 to
      9.2% (144/1565) in 1991. Mathematical modelling has predicted that the level of
      susceptibility anticipated in the school age population in 1995 would have been
      sufficient to allow a resurgence of measles. Over half of the cases in the
      resulting epidemic would have occurred in people aged at least 10 years and,
      because mortality is higher in this older age group, between 30 and 60 deaths
      would have occurred. A mass campaign to immunise all children of school age is
      expected to cause an immediate reduction in disease transmission and prevent a
      substantial toll of morbidity and mortality.

PMID- 7529085
TI  - Effect of liposome-muramyl tripeptide combined with recombinant canine
      granulocyte colony-stimulating factor on canine monocyte activity.
AB  - Liposome-muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) has been shown to
      activate monocytes in vivo to become tumoricidal resulting in reduction in
      metastasis as well as prolongation of survival time in murine and canine tumor
      models. Granulocyte colony-stimulating factor (G-CSF) is a cytokine which will
      stimulate the proliferation of granulocytes as well as monocytes. Recombinant
      canine G-CSF (rcG-CSF) was administered to normal dogs as a method of increasing
      the monocyte population prior to in vivo monocyte activation using L-MTP-PE. rcG
      CSF administration resulted in a 3.5-fold increase in absolute monocyte counts
      and when combined with L-MTP-PE, resulted in an enhanced level of serum tumor
      necrosis factor-alpha activity compared to dogs treated with L-MTP-PE alone. G
      CSF alone did not affect monocyte cytostatic activity, however, dogs receiving G
      CSF had a significant increase in monocyte cytostatic activity following L-MTP
      PE. The combined use of CSFs and effector cell activators deserves further
      evaluation in clinical trials.

PMID- 7529091
TI  - Occupational acquisition of acute hepatitis B infection by health care workers:
      England and Wales, 1985-93.

PMID- 7529090
TI  - Rubella surveillance to June 1994: third joint report from the PHLS and the
      National Congenital Rubella Surveillance Programme.
AB  - A downward trend in the incidence of acquired rubella in England and Wales was
      reversed in 1993 when there were local outbreaks. These affected young adult
      males in particular, especially those living in college residences. Some spread
      to local antenatal populations occurred. Twenty-five confirmed infections were
      reported in pregnant women, most of whom were young and in their first pregnancy;
      this compares with totals of 12 and two in 1991 and 1992, respectively. Reports
      of congenital rubella have not risen since the 1993 outbreaks. Diagnosis lags
      behind birth, however, and further evaluation may be needed. Notifications of 14
      infants, including one set of triplets, born with congenital infection since the
      beginning of 1991 have been received. Nine of the 12 mothers were immigrants, and
      three of these acquired their infection abroad. Data on antibody prevalence have
      revealed a large pool of susceptible males aged 10 to 25 years, which indicates
      that outbreaks in males would continue for some years if no action were taken.
      The national measles and rubella vaccination campaign in schools this month
      should abolish the difference in susceptibility between boys and girls up to 16
      years of age and hasten progress towards the interruption of rubella transmission
      in the United Kingdom. Susceptibility in girls aged 13 to 14 years rose to 5.8%
      in 1993 from an average of 3.6% between 1986 and 1992. This suggests that the
      vaccination of schoolgirls has recently declined, but this component of the
      selective rubella vaccination programme will be discontinued after the measles
      and rubella campaign.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529092
TI  - Malaria in Rajasthan.

PMID- 7529095
TI  - Spa pools: maintain and enjoy.

PMID- 7529094
TI  - Legionnaires' disease in England and Wales.

PMID- 7529093
TI  - Plague in India: restrictions eased.

PMID- 7529097
TI  - Candida albicans expresses a fibronectin receptor antigenically related to alpha
      5 beta 1 integrin.
AB  - Cell adhesion molecules, by regulating host-micro-organism interaction, play a
      major role in the pathogenesis of infectious diseases. The present study was
      undertaken to investigate the expression of the fibronectin (FN) receptor
      prototype, alpha 5 beta 1 integrin, on Candida albicans and its involvement in
      the adhesion to FN. By immunofluorescence and fluorescence activated cell sorter
      (FACS) analysis, several monoclonal antibodies (mAbs) directed against human
      alpha 5 or beta 1 integrin subunits, or two different antisera to FN receptor
      positively stained C. albicans yeast and germ tube phases, this immunoreactivity
      increasing upon germ tube transition. Twenty-five to thirty per cent of
      [3H]glucose-labelled Candida yeasts specifically adhered to FN and this adhesion
      was increased upon germ tube transition. C. albicans yeast and germ tube forms
      bound to an RGD-containing 120 kDa tryptic fragment of FN and adhesion to FN was
      markedly inhibited by GRGDSP, but not GRGESP peptides. Moreover, binding of both
      C. albicans phases to FN was strongly inhibited by anti-alpha 5 SAM-1 mAb, or
      both anti-fibronectin receptor (FNr) antisera. Overall these results indicate
      that C. albicans yeast and germ tube phases express a receptor antigenically
      related to alpha 5 beta 1 integrin which mediates their adhesion to FN. The alpha
      5 beta 1 integrin-like receptor expression on C. albicans could be relevant for
      fungus-host interaction and in the dissemination process of Candida infection.

PMID- 7529098
TI  - [Demonstrating antibodies against hepatitis C virus in transfusion practice.
      Viral Hepatitis Working Group of the Societe Francaise de la Transfusion
      Sanguine].

PMID- 7529099
TI  - [Collection and manipulation of human hematopoietic cell lines].

PMID- 7529096
TI  - Immunization with a multiple antigen peptide containing defined B- and T-cell
      epitopes: production of bactericidal antibodies against group B Neisseria
      meningitidis.
AB  - Previous analysis of the class 1 outer-membrane (OM) protein of Neisseria
      meningitidis has identified discrete epitopes to be potential targets for immune
      attack. The conformation of these epitopes is important for inducing antibodies
      which can react with the native protein and promote complement-mediated lysis of
      the meningococcus. The multiple antigen peptide (MAP) system, which consists of
      an oligomeric branching lysine core to which are attached dendritic arms of
      defined peptide antigens, confers some conformational stability and also allows
      for the preparation of immunogens containing both B-cell and T helper (Th)-cell
      epitopes. In this study, MAPs were synthesized to contain (i) the subtype P1.16b
      meningococcal class 1 protein B-cell epitope (B-MAP), and (ii) the P1.16b epitope
      in tandem with a defined Th-cell epitope, chosen from tetanus toxin (BT-MAP). The
      B-MAP was nonimmunogenic in animals. In contrast, incorporation of the Th-cell
      epitope into BT-MAP induced a strong humoral response towards the class 1 protein
      B-cell epitope. Antisera from immunized mice and rabbits reacted in ELISA with
      synthetic peptides containing the B-cell epitope, and also cross-reacted with
      meningococcal OMs from strains of subtype P1.16b and P1.16a. Murine and rabbit
      antisera showed similar reactivity and epitope specificity, but did not react
      with denatured class 1 protein in Western blotting, indicating the predominance
      of antibodies directed towards conformational epitopes. The antisera from rabbits
      immunized with BT-MAP promoted complement-mediated bactericidal killing not only
      of the homologous meningococcal subtype P1.16b strain but also of subtype P1.16a.

PMID- 7529100
TI  - Palliative medicine overtakes euthanasia.

PMID- 7529101
TI  - The assessment of need for bereavement follow-up in palliative and hospice care.
AB  - This paper describes a postal survey of palliative care services and teams which
      were identified in the 1992 Directory of Hospice Services in the UK and Ireland.
      Its aims were to investigate how units assess the need for bereavement follow-up,
      and to determine the nature and extent of services provided for bereaved adults.
      We sent out 397 questionnaires, of which 187 were returned, a response rate of
      47%. Results indicate that 156 respondents (84%) provided follow-up and a further
      13 (7%) were planning bereavement services. Only 48 (25%) units undertook formal
      standardized risk assessment procedures to allocate appropriate services; in 41
      units (85%) this was done by a nurse. Of the remaining 125 units, 58 (46%)
      reported basing their decisions on clinical impressions. Content analysis of the
      formal assessment instruments revealed 39 subcategories, which were broadly
      grouped into three areas: circumstantial factors at or near to the time of death,
      personal factors and social factors. Recommendations are made for further study.

PMID- 7529102
TI  - Ethical issues in palliative care research.
AB  - Much has been written about the ethics of experimental research upon human
      subjects, particularly where such subjects can be said to be in a vulnerable
      position in relation to the researcher. This paper attempts to address such
      questions with reference to people who are dying. A case is made to defend the
      view that no research is morally justifiable with this client group. Less extreme
      views are also explored. One justification for such research activity comes from
      a rights-based perspective and another from the weighing of benefits and harms.
      In the process of exploring these issues, the author attempts to demonstrate that
      no research methodology can be said to be benign.

PMID- 7529104
TI  - Thiamine deficiency in patients admitted to a palliative care unit.
AB  - This study looks at the clinical and thiamine status of 50 terminally ill
      patients who were admitted to a palliative care unit. Thiamine levels were found
      to be abnormally low in 28% of the patients and borderline in a further 36%.
      Cognitive impairment, as measured by the mini-metal state examination (MMSE) of
      Folstein, Folstein and McHugh, was present in 68% of those tested and a
      significant correlation was found between the MMSE status and thiamine levels.

PMID- 7529103
TI  - The use of nebulized opioids for breathlessness: a chart review.
AB  - Breathlessness secondary to both cancer and non-malignant disease is a
      distressing, exhausting symptom which, to date, has been difficult to control.
      This paper reports a chart review undertaken on patients referred to the Ottawa
      Civic Hospital's Palliative Care Service over the 18-month period from 1 January
      1992 to 30 June 1993. The intent of the review was to assess the recorded
      efficacy and safety of nebulized opioid use on patients with complaints of
      dyspnoea. Fifty-four patients were treated and subjective data have been
      compiled. The treatment was found to be effective, safe and convenient for the
      majority of the patients studied. In addition, nebulized opioids have been
      demonstrated as a treatment modality which is feasible for self-administration by
      the patient at home.

PMID- 7529105
TI  - Management of spinal infusions in palliative care.
AB  - Spinal analgesia can provide excellent pain relief for a small group of patients
      in whom conventional modalities have failed. The role of spinal analgesia in the
      palliative care setting is discussed and illustrated by the experience at St
      Gemma's Hospice over a two-year period. Special emphasis is placed on the
      difficulties that may need to be overcome when using this form of analgesia. The
      management of spinal infusions can produce some unique problems to the hospice or
      home care team, but the benefits often far outweight the difficulties.

PMID- 7529106
TI  - Resuscitation and non-resuscitation orders.

PMID- 7529107
TI  - The effect of caffeine on prostaglandin output from the guinea-pig uterus.
AB  - 1. Caffeine increased the outputs of prostaglandin F2 alpha (PGF2 alpha), PGE2
      and 6-keto-PGF1 alpha from the guinea-pig uterus on days 7 and 15 of the oestrous
      cycle. The effect on PGE2 output depended on the age of the animals and was
      absent in younger guinea-pigs (< 4 months). Theophylline also stimulated the
      outputs of PGF2 alpha and 6-keto-PGF1 alpha, but not the output of PGE2, from the
      day 7 guinea-pig uterus. 2. The stimulatory effects of caffeine on the outputs of
      PGF2 alpha, PGE2 and 6-keto-PGF1 alpha from the guinea-pig uterus were not
      prevented by lack of extracellular calcium, ryanodine or ruthenium red (both
      inhibitors of calcium release via the ryanodine receptor), although the increase
      in PGF2 alpha output tended to be slower when extracellular calcium was absent.
      Also, ryanodine flattened and broadened the peak of increased PGF2 alpha release.
      3. The calmodulin antagonists, W-7 and trifluoperazine, had no inhibitory effect
      on the caffeine-stimulated increases in uterine prostaglandin output. In fact, W
      7 (but not trifluoperazine) greatly potentiated the action of caffeine on uterine
      PGF2 alpha output, but had little or no potentiating effect on the action of
      caffeine on uterine PGE2 and 6-keto-PGF1 alpha outputs. 4. TMB-8, an
      intracellular calcium antagonist, inhibited the increase in PGF2 alpha output
      produced by caffeine without preventing the increases in outputs of PGE2 and 6
      keto-PGF1 alpha. 5. These studies suggest that caffeine stimulates uterine PGF2
      alpha synthesis and release by a mechanism dependent upon intracellular calcium,
      but this mechanism is not mediated by activation of any of the three well
      characterized ryanodine receptors or by calmodulin. Furthermore, the increases in
      the synthesis and release of PGE2 and 6-keto-PGFI alpha. in the guinea-pig uterus
      induced by caffeine appear to involve mechanism(s) different from that which
      stimulates PGF2 alpha production.

PMID- 7529108
TI  - Generation by the phosphoramidon-sensitive peptidases, endopeptidase-24.11 and
      thermolysin, of endothelin-1 and c-terminal fragment from big endothelin-1.
AB  - 1. Phosphoramidon, a potent inhibitor of endopeptidase-24.11 (E-24.11) and
      thermolysin, has been shown to reduce the hypertensive effect of exogenous big
      endothelin-1 (big ET-1) in rats. To examine whether E-24.11 or thermolysin
      convert big ET-1 to endothelin-1 (ET-1) and C-terminal fragment (CTF), the
      effects on porcine and human big ET-1 of each of the purified enzymes were
      compared in vitro. 2. For E-24.11, the relative rates of hydrolysis were ET-1 >
      CTF >> big ET-1. The relative half-lives for hydrolysis of 3 nmol of each peptide
      by 200 ng enzyme were: big ET-1 > 24 h; ET-1, 37 min; CTF, 57 min. For
      comparison, the half-life for hydrolysis of substance P under similar conditions
      was 2.1 min. 3. For thermolysin the relative rates of hydrolysis were found to be
      big ET-1 > CTF > ET-1. The relative half-lives for hydrolysis of 3 nmol peptide
      by 50 ng enzyme were: big ET-1, 25 min; ET-1, 56 min; CTF, 47 min. 4. Because the
      low rate of conversion of big ET-1 to ET-1 by E-24.11 did not yield sufficient ET
      1 for h.p.l.c. quantification a RIA specific for ET-1(16-21) was used to study
      further the hydrolysis of big ET-1 by E-24.11. Incubation of big ET-1 (0.2-2
      nmol) with E-24.11 (4-400 ng) generated ET-1 levels of between 1.7 and 33 pmol
      measured by RIA. Incubation of big ET-1 (2 nmol) with E-24.11 (40 ng) for 8 h
      showed that steady state levels of ET-1 were achieved after 4 h indicating that
      the rate of ET-1 degradation was then equal to the formation of new ET-1.
      Characterization of the immunoreactivity by h.p.l.c. and RIA confirmed that
      authentic ET-1 had been produced, but the yield was insufficient for verification
      by mass spectrometry.5. Both ET-l-like and CTF-like peaks were detected at 214 nm
      when the products of big ET-1 hydrolysis by thermolysin were resolved by h.p.l.c.
      RIA and mass spectrometry confirmed the production of ET-1 with amounts in the
      range 120-160 pmol.6. The hydrolysis profile of ET-1 by E-24.11 and thermolysin
      shows that both enzymes have some common cleavage sites consistent with their
      similar specificities hydrolysing on the amino side of a hydrophobic residue.7.
      Thermolysin, for which 3D structural information is available, may represent a
      better model for endothelin converting enzyme (ECE) action than E-24.11 and could
      be useful for the design of ECE inhibitors. Since E-24.11 can both synthesize and
      hydrolyse ET-1, the presence of E-24.11 in membrane fractions or in partially
      purified ECE preparations may produce misleading estimates of ECE activity.

PMID- 7529109
TI  - Abolition of flow-dependent EDRF release before that evoked by agonists in
      hypercholesterolaemic rabbits.
AB  - 1. We have used a pulsatile cascade bioassay system to investigate the effects of
      dietary-induced hypercholesterolaemia on EDRF release evoked by acetylcholine and
      by the oscillatory and time-averaged components of flow, in isolated segments of
      rabbit abdominal aorta. 2. Flow pulsatility (frequency range 0.1-10 Hz) was
      studied with constant flow (9 ml min-1) at a pulse pressure amplitude of 2 mmHg.
      Frequency-related EDRF release, maximal at 6 Hz, was slightly attenuated after 4
      weeks and abolished after 8 weeks of cholesterol feeding. 3. Time-averaged shear
      stress was manipulated with dextran (1-4% w/v, 80000 mol. wt.), to increase
      perfusate viscosity. EDRF release induced by increased perfusate viscosity was
      unaffected after 4 weeks but abolished after 8 weeks of cholesterol feeding. 4.
      Endothelium-dependent relaxations to acetylcholine (0.1-10 microM) were not
      influenced after 4 weeks and only partially attenuated (by 60% of the maximal
      response, EC50 unchanged at 6.45 +/- 0.04 vs. 6.4 +/- 0.1 microM) after 8 weeks
      of cholesterol feeding. 5. Blood cholesterol levels were significantly (P <
      0.001) increased after 4 weeks (26 +/- 3.6 vs 2.6 +/- 0.6 mmol l-1) and 8 weeks
      (56.2 +/- 3.8 vs 1.3 +/- 0.1 mmol l-1) of cholesterol feeding but after 8 weeks
      plasma L-arginine levels were not significantly different from the age-matched
      controls (0.2 +/- 0.05 vs. 0.19 +/- 0.04 mmol l-1). 6. We conclude that
      hypercholesterolaemia impairs flow-related (pulsatile- and time-averaged shear
      induced) EDRF release earlier than acetylcholine-induced relaxation in rabbit
      aorta. This is consistent with the view that different transduction mechanisms
      mediate EDRF release in response to agonists and flow.

PMID- 7529110
TI  - Nitric oxide as a mediator of the laxative action of magnesium sulphate.
AB  - 1. Magnesium sulphate was studied for its effects on diarrhoea, fluid secretion,
      gastrointestinal transit and nitric oxide (NO) synthase activity in rats. 2. At a
      dose of 2 g kg-1 orally magnesium sulphate produced diarrhoea that was delayed in
      onset and intensity in a dose-related manner by the NO synthase inhibitor NG
      nitro-L-arginine methyl ester (L-NAME). This was prevented by the NO precursor, L
      arginine and the NO donating compound, isosorbide-5-mononitrate (IMN). 3. Nitric
      oxide synthase activity was stimulated in gut tissue from rats given magnesium
      sulphate and this was inhibited by L-NAME. Dexamethasone (1 mg kg-1, i.p.), an
      inhibitor of inducible NO synthase, had no effect on magnesium sulphate-induced
      diarrhoea. 4. Magnesium sulphate stimulated fluid and electrolyte accumulation in
      the intestinal lumen; these effects were prevented by L-NAME but not D-NAME. 5.
      Gastrointestinal transit of a non-absorbable marker (charcoal suspension) was
      increased by oral magnesium sulphate from a mean value of 54.1% to 72.9% (P <
      0.01), and this was prevented by pretreatment with L-NAME. 6. The results
      demonstrate that oral magnesium sulphate produces diarrhoea in rats by increasing
      the accumulation of fluid in the intestinal lumen and enhancing flow from the
      proximal to distal intestine. The mechanism involves release of NO, probably
      through stimulation of the constitutive form of NO synthase. Whether or not the
      effects of magnesium sulphate are due to an osmotic action or an intrinsic effect
      of the magnesium or sulphate ions cannot be determined from these experiments.

PMID- 7529112
TI  - Effect of 7-nitro indazole on neurotransmission in the rat vas deferens:
      mechanisms unrelated to inhibition of nitric oxide synthase.
AB  - 1. The effect of the nitric oxide synthase (NOS) inhibitor, 7-nitro indazole (7
      NI), on sympathetic and purinergic neurotransmission in the rat isolated vas
      deferens preparation has been studied. 2. 7-NI (50-200 microM) caused a dose- and
      frequency-dependent inhibition of the phasic (predominantly purinergic)
      contractile response of the rat vas deferens to electrical (field) stimulation
      (100 V, 0.5 ms). Greatest inhibition occurred at lower frequencies of stimulation
      (0.1-10 Hz). The sustained tonic contractile response (predominantly
      noradrenergic) was inhibited only at a high frequency of stimulation (60 Hz) and
      only at the highest concentration of 7-NI studies (200 microM). 3. 7-NI (100
      microM) significantly reduced the contractile response of the vas deferens to
      exogenous ATP (20 microM-5 mM) and the stable P2X purinoceptor agonist, alpha,
      beta-methylene ATP (2.5 and 25.0 microM) but was without effect on contractions
      due to noradrenaline (0.1-50 microM) indicating a lack of antagonist effect on
      post-junctional alpha 1 adrenoceptors. 4. The effect of 7-NI (100 microM) on the
      phasic contractile response to field stimulation (0.1 and 2.0 Hz) was unaffected
      by preincubation of preparations with yohimbine (1.0 microM) or propranolol (0.01
      10.0 microM) indicating the absence of involvement of alpha 2- or beta
      adrenoceptors in this response. 5. 7-NI (50-600 microM) caused dose-related
      inhibition of contractions elicited by addition of a depolarizing concentration
      of KCl (64 mM). 6. The effect of 7-NI (100 microM) on the phasic contractile
      response to field stimulation (0.1 and 2.0 Hz) was unaffected by preincubation of
      preparations with L-arginine (1 mM). Neither L-arginine (1 mM) nor NC nitro L
      arginine methyl ester (L-NAME, 100 LM) affected the response of the vas deferens
      to field stimulation at 0.1 or 2.0 Hz. Nitric oxide synthase (NOS) enzyme
      activity, measured as the conversion of[3H]-L-arginine to [3H]-citrulline, was
      not detectable in rat vas deferens homogenates.7. 7-Nr preferentially inhibits
      the purinergic component of the response of the rat vas deferens to field
      stimulation. The mechanism of action of 7-NI is not known but is not related to
      NOS inhibition. It seems likely that 7-NI combines an antagonist action at smooth
      muscle cell P2X-purinoceptors with the ability to inhibit the cellular influx of
      calcium ions. Although these hitherto unrecorded effects of 7-NI occur at
      relatively high concentrations, the effects described may contribute to the
      pharmacological effects of this NOS inhibitor.

PMID- 7529113
TI  - Involvement of enzymatic degradation in the inactivation of tachykinin
      neurotransmitters in neonatal rat spinal cord.
AB  - 1. The possible involvement of enzymatic degradation in the inactivation of
      tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat.
      2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization
      of a lumbar ventral root in the isolated spinal cord preparation was increased by
      a mixture of peptidase inhibitors, consisting of actinonin (6 microM),
      arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and
      thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly
      than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the
      saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented
      by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM)
      but not in the presence of both naloxone and a tachykinin receptor antagonist,
      GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the
      spinal cord evoked an increase in the release of SP from the spinal cord. The
      amount of SP released was significantly augmented by the mixture of peptidase
      inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal
      cords. These fractions showed degrading activities for SP and NKA and the
      activities were inhibited by the mixture of peptidase inhibitors. The degrading
      activity for NKA was higher than that for SP and the inhibitory effect of the
      mixture for NKA was more marked than that for SP. Although some other fractions
      obtained from homogenates of spinal cords showed higher degrading activities for
      SP, these activities were insensitive to the mixture of peptidase inhibitors. 6.
      Effects of individual peptidase inhibitors on the enzymatic degradation of SP and
      NKA by synaptic membrane fractions were examined. Thiorphan, actinonin and
      captopril inhibited SP degradation, while thiorphan and actinonin, but not
      captopril, inhibited NKA degradation. The potency of the inhibition of each
      peptidase inhibitor was lower than that of the mixture.7. The present results
      suggest that enzymatic degradation is involved in the inactivation of tachykinin
      neurotransmitters in the spinal cord of the neonatal rat.

PMID- 7529114
TI  - Adenosine-induced hyperpolarization of the membrane voltage in rat mesangial
      cells in primary culture.
AB  - 1. The effect of adenosine on membrane voltage and ion currents was studied in
      rat mesangial cells in primary culture. Membrane voltage was measured with the
      patch clamp technique in the slow- or fast whole cell configuration. The resting
      membrane voltage of mesangial cells was -48 +/- 0.5 mV. Adenosine (10(-8)-10(-3)
      M) induced a sustained and concentration-dependent hyperpolarization of membrane
      voltage (ED50 approximately 6 x 10(-7) M). Adenosine (10(-5) M) hyperpolarized
      the membrane voltage by 14 +/- 0.5 mV. During the hyperpolarization ion currents
      were monitored simultaneously. An increase of the outward current by 51 +/- 11%
      was observed. 2. An increase of the extracellular K+ concentration (from 3.6 to
      18.6 M) caused a depolarization of membrane voltage to -34 +/- 2 mV. In the
      presence of increased K+ the hyperpolarization of membrane voltage induced by
      adenosine was significantly attenuated by 61 +/- 5%. The K(+)-channel blocker,
      Ba2+ (5 x 10(-3) M) depolarized membrane voltage to -24 +/- 2 mV. In the presence
      of Ba2+ the adenosine-induced hyperpolarization was significantly inhibited by 72
      +/- 8%. 3. Preincubation of the adenosine antagonist, 8-phenyltheophylline (10(
      4) M) significantly inhibited the adenosine (10(-5) M) mediated membrane voltage
      response by 67 +/- 8%. The adenosine agonists 5-N-ethylcarboxamidoadenosine
      (NECA), R-(-)N6-(2-phenylisopropyl)adenosine (R-(-)-PIA), S-(+)-N6-(2
      phenylisopropyl)adenosine (S-(+)-PIA), N6-[2-(3,5-dimethoxyphenyl)-2-(2
      methylphenyl)-ethyl]adenosine (DPMA), and 2-chloroadenosine (2-CA) also
      hyperpolarized membrane voltage of mesangial cells. The rank order of potency of
      the agonists at 10-5 M was NECA> adenosine = > R-(-)-PIA = DPMA = 2-CA > S-( + )
      PIA.4. Stimulation of cyclic AMP by forskolin induced a concentration-dependent
      hyperpolarization of membrane voltage (ED50 ~2 x 10-7 M). Application of
      forskolin (10-5 M) in the presence of adenosine(10-4 M) had no additive
      hyperpolarizing effect on the membrane voltage.5. Activation of protein kinase C
      by phorbol 12,13 dibutyrate (PDBu) induced a sustained depolarization of membrane
      voltage (ED50~ 5 x 10-9 M). In the presence of PDBu, adenosine (10-5 M) still
      hyperpolarized membrane voltage of mesangial cells.6. The data indicate that
      adenosine activates K+-conductance via an A2 receptor in mesangial cells; the
      activation of the K+-conductance, which is probably mediated by cyclic AMP led to
      a hyperpolarization of membrane voltage.

PMID- 7529111
TI  - Anti-ischaemic efficacy of a nitric oxide synthase inhibitor and a N-methyl-D
      aspartate receptor antagonist in models of transient and permanent focal cerebral
      ischaemia.
AB  - 1. We have recently developed a new model of transient focal ischaemia in the rat
      utilising topical application of endothelin-1 to the left middle cerebral artery
      (MCA). In order to validate this approach the present study assessed the
      neuroprotective efficacy of the NMDA receptor antagonist dizocilpine (MK-801) in
      the endothelin-1 model. The anti-ischaemic efficacy of the nitric oxide (NO)
      synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was subsequently
      evaluated, and contrasted with its efficacy against permanent focal ischaemia, to
      determine the utility of the endothelin-1 model for identification of novel
      pharmacoprotective agents. 2. MK-801 (0.12 mg kg-1 bolus, 108 micrograms kg-1 h-1
      infusion i.v., either 1 or 2.5 h pre-transient MCA occlusion (MCAO)) induced
      hypotension that persisted for approximately 1.5 h so that mean arterial blood
      pressure (MABP) at the time of MCAO was significantly lower in the 1 h group
      compared with control (MABP: 86 +/- 11, 68 +/- 6 and 84 +/- 4 mmHg (mean +/-
      s.d.) for saline, 1 h MK-801 and 2.5 h MK-801 groups respectively). The 2.5 h
      pretreatment schedule resulted in significant reduction (71%) in the volume of
      hemispheric damage (assessed 4 h post onset of ischaemia) while the 1 h
      pretreatment schedule did not (volumes of hemispheric damage: 59 +/- 38, 51 +/-
      51 and 17 +/- 28 mm3 for saline, 1 h and 2.5 h MK-801 groups). 3. Thus the
      considerable neuroprotective effect of MK-801 in the endothelin-1 model of
      transient focal cerebral ischaemia was highly sensitive to drug-induced
      hypotension. This result is in contrast to previous studies of permanent MCAO
      where MK-801-induced hypotension did not compromise its neuroprotective action.4.
      L-NAME (3 mg kg-1, i.v. 30 min pre-MCAO) moderately, but significantly, reduced
      (16%) the volume of ischaemic damage 4 h post-permanent MCA occlusion, whereas
      the 29% reduction in volume of damage achieved in the model of transient focal
      ischaemia did not attain significance due to the greater variability associated
      with this model. L-NAME did not significantly alter MABP in either model.5. The
      modest neuroprotection achieved with NO synthase inhibition suggests NO is of
      relatively minor importance as a mediator of neurotoxicity following permanent
      focal cerebral ischaemia. In addition the comparable efficacy of L-NAME against
      transient focal ischaemia suggests the presence of reperfusion does not enhance
      the contribution of NO to neuronal injury in the acute (4 h) phase following a
      focal ischaemic insult.

PMID- 7529115
TI  - On the nature of the 5-HT receptor subtype inhibiting acetylcholine release in
      the guinea-pig ileum.
AB  - 1. The nature of the 5-hydroxytryptamine (5-HT) receptor subtype controlling
      acetylcholine release and contraction induced by stimulation of the neurokinin
      NK3 receptor has been studied in the longitudinal muscle-myenteric plexus
      preparation from guinea-pig ileum. 2. In preparations preloaded with [3H]
      choline, the selective NK3 agonist, senktide, produced a concentration-dependent
      increase in tritium overflow, an index of [3H]-acetylcholine release. Low
      concentrations of neurokinin B, also markedly increased tritium efflux. 3. The
      senktide-induced acetylcholine release was markedly increased by the same
      concentration of methysergide and mesulergine. The 5-HT2A/2C agonist DOI (1
      microM) inhibited the tritium overflow while 8-OH-DPAT, sumatriptan and
      ketanserin (1 microM each) were without effect on the senktide-induced tritium
      efflux. 4. The contractile response to senktide in the guinea-pig ileum was
      attenuated by atropine, 0.1 microM. Methysergide, a 5-HT1/2 receptor antagonist,
      and mesulergine, a 5-HT2A/2B/2C receptor antagonist, (1 microM each), enhanced
      the contractile effect of the NK3 receptor agonist. 5. It is concluded that the
      acetylcholine release induced by a NK3 receptor agonist is inhibited by
      stimulation of a 5-HT receptor, possibly of the 5-HT2C or 5-HT2C subtype.

PMID- 7529117
TI  - Endoscopic diagnosis and treatment of esophageal cancer.
AB  - Esophageal carcinoma is one of the deadliest malignant tumors. This article
      reviews its epidemiology, etiology, and clinical and endoscopic presentation, as
      well as methods for proper staging to identify the patients who will not benefit
      from surgery and require palliative therapy. The various treatment options are
      discussed in detail with an emphasis on the latest endoscopic palliative
      measures.

PMID- 7529118
TI  - Management of malignant esophageal stricture with esophageal dilation and
      esophageal stents.
AB  - Esophageal dilatation and endoprosthesis insertion are very useful techniques in
      the palliation of malignant esophageal strictures. Patients with
      tracheoesophageal fistula or tumors poorly responsive to dilation or other
      therapies will achieve benefit from esophageal stent placement. Although further
      studies are needed, it appears that the use of expansile metallic stents may be
      advantageous compared with the standard plastic stents.

PMID- 7529119
TI  - Endoscopic laser therapy for esophageal cancer.
AB  - Neodymium:YAG laser therapy has been shown to be a safe and effective palliative
      treatment for esophageal cancer. Exophytic tumors in a straight segment of the
      mid- and distal esophagus are most amenable to therapy. Perforation or fistula,
      the most serious complications, occur in less than 5% of patients.

PMID- 7529120
TI  - Hepatitis B virus reverse transcriptase and its many roles in hepadnaviral
      genomic replication.
AB  - The replication of hepatitis B virus DNA proceeds through reverse transcription
      of a pregenomic RNA intermediate, a reaction that takes place within viral
      nucleocapsids and is catalyzed by the viral P protein. P protein is involved in
      all phases of the reaction, serving as (a) a recognition factor for the selective
      encapsidation of the pregenomic RNA template; (b) the protein primer for the
      initiation of minus strand DNA synthesis; (c) the reverse transcriptase and DNA
      polymerase involved in strand elongation; and (d) the RNaseH activity required to
      remove RNA template prior to plus strand synthesis. P protein is capable of site
      specific RNA recognition, specifically binding to a stem-loop structure at the 5'
      end of pregenomic RNA. This interaction is required for both RNA encapsidation
      and reverse transcription.

PMID- 7529116
TI  - Pharmacological characterization of rabbit corpus cavernosum relaxation mediated
      by the tissue kallikrein-kinin system.
AB  - 1. The roles of the tissue kallikrein-kinin system and nitric oxide (NO) release
      in Phoneutria nigriventer venom-induced relaxations of rabbit corpus cavernosum
      (RbCC) smooth muscle have been investigated by use of a bioassay cascade. 2.
      Phoneutria nigriventer venom (10-30 micrograms), porcine pancreatic kallikrein
      (100 mu), rabbit urinary kallikrein (10 mu), bradykinin (BK, 0.3-3 nmol),
      acetylcholine (ACh, 0.3-30 nmol) and glyceryl trinitrate (GTN, 0.5-10 nmol)
      caused relaxations of the RbCC strips. Captopril (1 microM) substantially
      potentiated Phoneutria nigriventer venom- and BK-induced RbCC relaxations without
      affecting those elicited by GTN. 3. The bradykinin B2 receptor antagonist, Hoe
      140 (D-Arg-[Hyp3,Thi5,D- Tic7,Oic8]-BK, 50 nM), aprotinin (10 micrograms ml-1)
      and the tissue kallikrein inhibitor, Pro-Phe-Aph-Ser-Val- Gln-NH2 (KIZD-06, 1.3
      microM) significantly inhibited Phoneutria nigriventer venom-induced RbCC
      relaxations, without affecting those provoked by GTN and ACh. The B1 receptor
      antagonist, [Leu9]des Arg10BK (0.5 microM) and soybean trypsin inhibitor (SBTI,
      10 micrograms ml-1) had no effect on Phoneutria nigriventer venom-induced RbCC
      relaxations. 4. The relaxations induced by Phoneutria nigriventer venom, porcine
      pancreas kallikrein, BK and ACh were significantly inhibited by N omega-nitro-L
      arginine methyl ester (L-NAME, 10 microM) but not by D-NAME (10 microM). L-NAME
      did not affect GTN-induced relaxations. L-Arginine (300 microM), but not D
      arginine (300 microM), significantly reversed the inhibitory effect of L-NAME. 5.
      Our results indicate that Phoneutria nigriventer venom activates the tissue
      kallikrein-kininogen-kinin system in RbCC strips leading to NO release and
      suggest a functional role for this system in penile erection.

PMID- 7529121
TI  - CD46, a primate-specific receptor for measles virus.
AB  - Measles virus normally infects only primate cells. The receptor for measles virus
      has recently been shown to be the complement regulator CD46, also known as
      membrane cofactor protein. Transfection of rodent cells with human CD46 renders
      them susceptible to the virus, suggesting that transgenic animals may prove
      useful for testing antiviral agents and vaccines.

PMID- 7529122
TI  - ME1-antibody labelling of primary bronchogenic tumours and extrapulmonary
      malignancies.
AB  - ME1 is a monoclonal antibody which is generated by the use of a mesothelioma cell
      line (SPCIII). The antibody has a preferential reaction to antigens on
      mesothelial and mesothelioma cells. In a prospective study we determined the
      reactivity in frozen sections from malignant mesotheliomas (two cases, positive
      controls), lung tumours (115 cases) and other malignant tumours (23 cases). The
      two malignant mesotheliomas were immunoreactive in most of the tumour cells. The
      reaction was strong, often with a diffuse staining of the cytoplasm and in some
      tumour cells there was heavy staining of the cell membrane. Five adenocarcinomas
      of the lung (9%), one large cell carcinoma (10%) and 18 squamous cell carcinomas
      of the lung (41%) were positive (defined as tumours containing more than 10%
      positive tumour cells with a strong reaction). The same was true for seven out of
      23 (30%) extrapulmonary malignancies. The overall nosologic specificity of ME1
      was 76%. Twenty out of the 26 ME1-positive lung tumours and six out of seven ME1
      positive extrapulmonary malignancies were also positive for one or more markers,
      which is considered characteristic of carcinomas. The six negative lung tumours
      were squamous cells carcinomas and the negative extrapulmonary tumour was a
      meningeoma; all of them with a morphology different to malignant mesothelioma. In
      conclusion, when frozen sections are available, ME1 might be useful in the
      differential diagnosis of malignant tumours. However, a positive reaction is not
      specific for malignant mesothelioma.

PMID- 7529123
TI  - The interleukin-2 and interleukin-4 receptors studied by molecular modelling.
AB  - BACKGROUND: Interleukin-2 (IL2) and interleukin-4 (IL4) are members of the four
      helix bundle family of cytokines, whose receptors show similarity to each other
      and to the growth hormone receptor fold. These proteins help to control, among
      other things, the rate of clonal expansion of lymphocytes, and thus play an
      important role in the regulation of the immune system. They are therefore of
      interest as transmembrane signalling proteins, as well as potential
      pharmaceutical targets. RESULTS: We have modelled structures of the extracellular
      components of the IL2 and IL4 receptors based on the structure of the complex of
      human growth hormone with its receptor, and incorporating the recently discovered
      shared gamma c chain. The models provide possible explanations for several
      experimental observations, including those from site-directed mutagenesis around
      the binding sites. Receptor residues that may be close to important side chains
      on IL2 and IL4 are identified and possible effects of their mutation are
      discussed. A comparison is made between the models and the growth hormone
      complex, and between the gamma c chain bound to IL2 and to IL4. CONCLUSIONS: The
      models offer structural explanations for observed behaviour such as the effects
      of mutation of the A- and D-helices of the cytokines. In addition, they may be of
      use in the identification of residues which may interact in the ligand-receptor
      interfaces, and which would therefore be worthy of further investigation.

PMID- 7529124
TI  - Comparison of three different crystal forms shows HIV-1 reverse transcriptase
      displays an internal swivel motion.
AB  - BACKGROUND: Reverse transcriptase (RT) from HIV-1 is responsible for replicating
      the single-stranded RNA genome to double-stranded DNA. The three-dimensional
      structure of RT shows that it is a strikingly asymmetric heterodimer consisting
      of two differently folded subunits (molecular weights 66 kDa and 51 kDa) with
      identical amino-terminal amino acid sequences (residues 1-428). The large active
      site cleft is composed of subdomains named 'finger', 'palm' and 'thumb'. There is
      also an RNAse H domain. RESULTS: We have compared four RT structures. The
      structures of two independent RT heterodimers comprising the asymmetric unit of
      an orthorhombic crystal form have been determined by molecular replacement and
      are noticeably different from each other. Comparison of the molecules in this
      crystal form with the two previously reported RT structures shows a related
      pattern of variations in relative sub domain positions. The structural
      differences can be described as a molecular twist between the polymerase active
      site located on the finger and palm domains of p66 and the rest of the molecule.
      This twist occurs around an axis which runs from the p66 palm domain through the
      p66/p51 connection domain interface and which exits below the RNAse H domain.
      CONCLUSIONS: From the differences in the four RT structures we infer that the
      molecule has a specific flexibility that allows rotation of the polymerase active
      site relative to the rest of the molecule. The observed swivelling motion of RT
      may allow the polymerase to accommodate the rotational and translational
      movements of the growing nucleic acid duplex, which present an especial problem
      for RT because it uses an asymmetric molecule (tRNA(Ly3)) as a primer for first
      strand synthesis.

PMID- 7529125
TI  - Phorbol ester stimulates acetylcholine synthesis in cultured endothelial cells
      isolated from porcine cerebral microvessels.
AB  - Acetylcholine (ACh) is one of the factor which induces vasodilation through the
      release of endothelium-derived relaxing factor. The aim of this study was to
      clarify whether endothelial cells can synthesize ACh and the types of substance
      which regulate the synthesis of ACh in endothelial cells. We determined the ACh
      content of endothelial cells isolated from porcine cerebral microvessels and of
      the culture medium. ACh was detected in the medium after 12 h incubation in the
      presence of diisopropylfluorophosphate, a non-specific cholinesterase inhibitor,
      and increased linearly up to 24 h. Phorbol 12-myristate 13-acetate (PMA, 10(-7)
      M) increased the ACh content of the medium in a dose-dependent manner. The effect
      of PMA was most apparent between 12 and 24 h after treatment, and was inhibited
      by cycloheximide. Calphostin C, a specific inhibitor of protein kinase C (PKC),
      did not inhibit the effect of PMA. Dioctanoyl glycerol, a specific activator of
      PKC, did not increase the intracellular ACh content or the amount released into
      the culture medium. ACh synthesis was not inhibited by bromoacetylcholine, a
      specific inhibitor of choline acetyltransferase (ChAT). PMA treatment did not
      affect the specific activity of ACh synthesis in endothelial cells. These data
      show that endothelial cells are able to synthesize ACh, and that ACh synthesis is
      up-regulated by PMA through the PKC independent mechanism via protein induction.
      The enzyme which synthesizes ACh in endothelial cells is not ChAT. The increase
      in ACh synthesis induced by PMA may not be due to induction of the ACh synthetic
      enzyme.

PMID- 7529126
TI  - Prostacyclin enhances the evoked-release of substance P and calcitonin gene
      related peptide from rat sensory neurons.
AB  - Prostacyclin (PGI2) is a potent prostanoid producing various symptoms of
      inflammation, including an increased sensitivity to noxious stimulation. One
      component of these PGI2-mediated actions may involve activation or sensitization
      of sensory neurons to enhance release of neuroactive peptides. We, therefore,
      examined whether PGI2 and carba prostacyclin (CPGI2), a stable analog of PGI2,
      could alter the resting and evoked release of the neuropeptides, substance P (SP)
      and calcitonin gene-related peptide (CGRP) from embryonic rat sensory neurons
      grown in culture. Treating isolated sensory neurons with CPGI2 (10-1000 nM) for
      30 min caused a 3-fold increase in the resting release of both peptides. One nM
      CPGI2, a concentration that did not alter the resting release, significantly
      enhanced neuropeptide release evoked by capsaicin, 100 nM bradykinin, or 40 mM
      KCl. Similarly, 10 nM PGI2 did not alter resting release, but augmented capsaicin
      stimulated release of SP and CGRP 2-3 fold. In contrast, prostaglandin F2 alpha
      was ineffective in altering either resting or capsaicin-evoked peptide release.
      Our results demonstrate that low concentrations of PGI2 sensitize sensory neurons
      to other stimuli, whereas higher concentrations evoke release directly. This PGI2
      induced augmentation of neuropeptide release may be one mechanism contributing to
      neurogenic inflammation.

PMID- 7529127
TI  - Split-course accelerated radiation therapy combined with carboplatin and 5
      fluorouracil for palliation of metastatic or unresectable carcinoma of the
      esophagus.
AB  - BACKGROUND: Patients with metastatic or unresectable carcinoma of the esophagus
      have poor survival, but often require palliation of dysphagia. METHODS: Twenty
      seven patients with unresectable carcinoma of the esophagus were treated with
      carboplatin, 5-fluorouracil, and split-course accelerated radiation therapy.
      Seventy-four percent of patients had adenocarcinoma, and 26% had squamous cell
      carcinoma. RESULTS: The regimen was well tolerated; 25% of the patients had
      disease improvement after completing therapy, although the majority of these
      patients had all of their disease within the radiation field. Ninety-three
      percent (13/14) of the patients who experienced disease progression during
      therapy progressed in areas treated with chemotherapy alone. Median survival was
      6 months. Fifty-nine percent of the 17 patients who presented with dysphagia
      achieved durable relief of that symptom. CONCLUSIONS: Carboplatin and 5
      fluorouracil have low activity in patients with metastatic esophageal cancer.
      However, in combination with radiation therapy, this regimen is tolerable when
      the primary goal is palliation of dysphagia near the end of life. Future studies
      should focus on identifying more active regimens with response and survival as
      endpoints.

PMID- 7529128
TI  - The frequency of apoptosis correlates with the prognosis of Gleason Grade 3
      adenocarcinoma of the prostate.
AB  - BACKGROUND: Although localized carcinomas are predominantly moderately
      differentiated (Gleason Grade 3), they demonstrate markedly different rates of
      progression. Previously, the authors reported a correlation between apoptosis and
      the malignant characteristics of carcinoma in the mouse prostate reconstitution
      model system and between apoptosis and Gleason grade in the human tumor. This
      study was undertaken to determine whether the frequency of apoptosis correlates
      with prognosis and to compare the prognostic significance of the apoptotic index
      with other prognostic features in Gleason Grade 3 carcinomas. METHODS: The
      apoptotic and mitotic indices of malignant and nonmalignant epithelium in 28
      consecutive radical prostatectomy specimens were determined for a carcinomas
      composed entirely of Gleason sum 6 (primary Grade 3, secondary Grade 3) with a
      clinical stage T2 classification. Each patient was followed for 5-9 years (median
      6, years). The indices, defined as the number of apoptotic and mitotic bodies in
      an H & E-stained section per 100 grids delineated by an ocular measuring field,
      were determined. The actuarial time to progression, defined as a sustained rise
      in the serum prostate specific antigen level greater than or equal to 0.4 ng/ml,
      was correlated with the apoptotic index, the mitotic index, tumor volume, and
      pathologic stage. RESULTS: Neither pathologic stage nor tumor volume differed
      significantly between the group of 19 patients (68%) with no progression and the
      other 9 whose tumor progressed. The median apoptotic index of the carcinomas was
      0.87 (range, 0.12-3.91). For patients with a low apoptotic index (< 0.87), the
      actuarial progression rate at 5 years was 7% +/- 14% (+/- 2 SE) compared with 50%
      +/- 26% for those with a high apoptotic index (P < 0.007). Mitotic index had no
      prognostic significance. CONCLUSIONS: In carcinoma of the prostate, apoptosis can
      be recognized in standard H & E sections and quantitated by light microscopy. The
      apoptotic index may provide additional prognostic information in the predominant
      grade of early stage carcinoma. Cancer 1995; 75:522-9.

PMID- 7529129
TI  - Sextant prostate biopsies. A histopathologic correlation with radical
      prostatectomy specimens.
AB  - BACKGROUND: Among patients with clinically localized prostate cancer,
      preoperative prediction of tumor volume and pathologic stage has been unreliable.
      This study examines the application of transrectal ultrasound-guided sextant
      biopsies to predict the extent of disease. METHODS: One hundred and two patients
      with clinically resectable prostate cancer were evaluated by systematic sextant
      biopsies. Radical prostatectomy specimens were embedded totally as whole mounts,
      tumor areas were outlined, and volume was measured using a digital scanner. The
      number of positive sextant biopsies was compared with age, race, preoperative
      prostate specific antigen (PSA), PSA density, DNA ploidy, pathologic stage,
      capsular and seminal vesicle involvement, prostate and tumor volume, and Gleason
      score. Stepwise logistic regression was used to determine if pathologic stage or
      tumor size could be predicted by these parameters. RESULTS: The number of
      positive sextant biopsies correlated with traditional prognostic indicators. When
      patients with three or fewer positive biopsies were compared with those with four
      or more positive sextant biopsies, significant differences were identified
      relative to preoperative PSA (P < 0.001), tumor volume (P < 0.001), pathologic
      stage (P < 0.001), Gleason score (P < 0.001), seminal vesicle involvement (P <
      0.001), and capsular penetration (P < 0.001). There were no significant
      differences based on age, race, DNA ploidy, and overall prostate volume. Logistic
      regression showed that patients with four or more positive sextant biopsies and
      high Gleason score had a greater likelihood of pT3 classification. Likewise, the
      probabilities of a tumor volume less than 0.5 ml could be predicted by the number
      of positive sextant biopsies and PSA alone. The number of positive sextant
      biopsies was the only factor that could predict a tumor volume greater than 4.0
      ml. CONCLUSION: The number of positive sextant biopsies appears to be an
      important prognostic indicator of pathologic (pT) classification and tumor
      volume. This information is valuable in selecting the treatment strategy for
      patients with prostate cancer.

PMID- 7529130
TI  - Natural killer cell activity in long-term survivors of testicular cancer.
      Influence of cytostatic therapy and initial stage of disease.
AB  - BACKGROUND: Patients with testicular cancer can be cured by cisplatin-based
      chemotherapy in many cases. Thus, concern about possible late toxicities of
      treatment is warranted. METHODS: In this investigation, the absolute number of
      natural killer (NK) cells according to their CD56+ phenotype, NK cell activity,
      and antibody dependent cellular cytotoxicity (ADCC) were investigated in 29
      patients with seminomas or nonseminomatous germ cell tumors (NSGCT) a median of
      31 months (range, 5-73 months) after termination of chemotherapeutic treatment.
      RESULTS: No difference in the absolute number of NK cells, NK cell activity, and
      ADCC was found between patients with testicular cancer after either standard
      polychemotherapy consisting of bleomycin, etoposide, and cisplatin (BEP) or
      monotherapy with carboplatin and healthy control subjects. When patients were
      analyzed further using multivariate analysis, a significant (P < 0.05)
      detrimental influence of BEP polychemotherapy versus carboplatin monotherapy on
      NK cell activity was found. Moreover, NK cell activity also depended
      significantly (P < 0.05) on the time elapsed after chemotherapy was administered,
      but normalized with time. Because the absolute number of NK cells was not
      affected, is was assumed that polychemotherapy induced a functional defect. In a
      subanalysis of patients with NSGCTs, metastases at diagnosis resulted in a
      significant (p < 0.05) and persistent stimulation of NK cell activity but not of
      ADCC. CONCLUSION: Cytostatic chemotherapy in patients with testicular cancer did
      not lead to compromised lytic effector cell function as assessed by NK cell
      activity and ADCC. However, a short, time-dependent reduction was found that also
      depended on the intensity of chemotherapeutic treatment. This finding related to
      the observation of a long-lasting stimulus of NK cell activity by initial
      metastases in patients with NSGCTs.

PMID- 7529132
TI  - Hemotoxicity by prolonged etoposide administration to mice can be prevented by
      simultaneous growth factor therapy.
AB  - In this study, we determined in vivo interactions between hemopoietic growth
      factors and etoposide (VP-16) to assess whether normal blood cell production
      could be maintained during chemotherapy if hemopoietic growth factors were
      simultaneously administered. Groups of mice were treated for 7 consecutive days
      with four different doses of VP-16 in combination with three different doses of
      erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF). In total,
      12 combinations of VP-16 plus EPO and 12 combinations of VP-16 plus G-CSF were
      thus evaluated. Intricate dose-response surfaces of the effects of the different
      treatments on colony-forming units-erythroid, reticulocytes, hematocrit, colony
      forming units-granulocyte/macrophage, and absolute neutrophil count were
      obtained, which revealed that: (a) simultaneous EPO administration was able to
      maintain reticulocyte production and to protect mice from VP-16 induced anemia;
      (b) simultaneous G-CSF administration was able to maintain granulocyte production
      and to protect mice from VP-16 induced neutropenia; (c) VP-16 dose escalation was
      feasible when EPO or G-CSF were simultaneously administered; and (d) no increased
      myelotoxicity on erythroid or granuloid progenitors was observed when EPO or G
      CSF was simultaneously administered with VP-16. These results suggest that in
      vivo either individual hemopoietic progenitors can become resistant against VP-16
      induced cell death by appropriate simultaneous growth factor administration or
      that the loss of overall cell amplification, induced by VP-16, can be compensated
      by extra amplification of surviving progenitors. Furthermore, these data indicate
      that a strict separation in time of cytostatic drug and growth factor treatment
      is not necessarily the optimal schedule with respect to the reduction of
      hemotoxicity.

PMID- 7529131
TI  - The use of digital image analysis of chromatin texture in Feulgen-stained nuclei
      to predict recurrence of low grade superficial transitional cell carcinoma of the
      bladder.
AB  - BACKGROUND: Identifying a marker enabling prediction of recurrence in the group
      of superficial transitional cell carcinomas (sTCCs) of the bladder remains an
      important challenge today. This report quantitatively describes chromatin
      patterns with respect to such sTCC recurrence. MATERIALS AND METHODS: Twenty-nine
      patients with sTCCs who did not exhibit tumor recurrence within a minimum of 24
      months were compared with 21 patients with sTCCs who exhibited tumor recurrence
      two or three times in a 24-month period, for a total of 74 sTCCs. Quantitative
      chromatin pattern description was performed by the digital cell image analyses of
      Feulgen-stained nuclei. Six morphonuclear parameters were thus described and
      subsequently used to determine a score, allowing biological behavior of sTCCs to
      be described, i.e., recurrence versus non-recurrence in one calculation step. DNA
      ploidy level was also determined in each sTCC by assessing its DNA histogram
      type. RESULTS: Of 32 patients with Grade 1 pathologically classified pTa/pT1
      tumors, DNA ploidy level determination permitted correct prediction of tumor
      nonrecurrence or recurrence of 13 (41%), whereas determination of the score
      values enabled prediction of nonrecurrence or recurrence of 25 (78%). Combining
      DNA ploidy level data and the score values enabled recurrence or nonrecurrence to
      be predicted for 29/32 of the patients (91%). CONCLUSIONS: The quantitative
      description of chromatin patterns by digital cell image analysis of Feulgen
      stained nuclei can provide helpful information, in addition to DNA ploidy level
      determination, in predicting tumor recurrence of low grade superficial
      transitional cell carcinomas of the bladder.

PMID- 7529133
TI  - DNA repair in the MYC and FMS proto-oncogenes in ultraviolet light-irradiated
      human HL60 promyelocytic cells during differentiation.
AB  - In order to better understand the role of transcription in cellular processing of
      damage in specific DNA sequences, we have used an in vitro differentiation system
      to modulate the activity of the MYC gene. When human HL60 promyelocytic cells
      differentiate in vitro, the transcriptional activity of the MYC gene is down
      regulated. We have shown that in the expressed MYC gene, 56% of UV-induced
      cyclobutane pyrimidine dimers (CPDs) are removed within 18 h and the transcribed
      strand is selectively repaired. However, late in differentiation, when the MYC
      gene is maximally down-regulated, only 15% of the CPDs are removed within the
      same period. During early differentiation, the MYC gene is regulated by a block
      to transcription elongation at the 5' end of the first intron. Our results reveal
      no significant difference in the rate of CPD removal between the restriction
      fragments upstream and downstream of this elongation block. Furthermore, both
      strands of each fragment exhibit similar repair characteristics. In contrast, the
      constitutively expressed FMS gene exhibits proficient removal of CPD in both the
      differentiated and undifferentiated cells. Furthermore, the repair appears to be
      more proficient at the 5' end (exon 1) than in the 3' end of the gene about 35
      kilobases downstream from exon 1. Since efficient repair of the active FMS gene
      is maintained in the differentiated cells the loss of repair competence seen in
      MYC is more likely associated with its reduced transcriptional activity than with
      a decrease in the overall repair capacity of the terminally differentiated cells.

PMID- 7529134
TI  - Genetic changes in primary and recurrent prostate cancer by comparative genomic
      hybridization.
AB  - Genetic changes leading to the development of prostate cancer and factors that
      underlie the clinical progression of the disease are poorly characterized. Here,
      we used comparative genomic hybridization (CGH) to screen for DNA sequence copy
      number changes along all chromosomes in 31 primary and 9 recurrent uncultured
      prostate carcinomas. The aim of the study was to identify those chromosome
      regions that contain genes important for the development of prostate cancer and
      to identify genetic markers of tumor progression. CGH analysis indicated that 74%
      of primary prostate carcinoma showed DNA sequence copy number changes. Losses
      were 5 times more common than gains and most often involved 8p (32%), 13q (32%),
      6q (22%), 16q (19%), 18q (19%), and 9p (16%). Allelic loss studies with 5
      polymorphic microsatellite markers for 4 different chromosomes were done from 13
      samples and showed a 76% concordance with CGH results. In local recurrences that
      developed during endocrine therapy, there were significantly more gains (P <
      0.001) and losses (P < 0.05) of DNA sequences than in primary tumors, with gains
      of 8q (found in 89% of recurrences versus 6% of primary tumors), X (56% versus
      0%), and 7 (56% versus 10%), as well as loss of 8p (78% versus 32%), being
      particularly often involved. In conclusion, our CGH results indicate that losses
      of several chromosomal regions are common genetic changes in primary tumors,
      suggesting that deletional inactivation of putative tumor suppressor genes in
      these chromosomal sites is likely to underlie development of prostate cancer.
      Furthermore, the pattern of genetic changes seen in recurrent tumors with the
      frequent gains of 7, 8q, and X suggests that the progression of prostate cancer
      and development of hormone-independent growth may have a distinct genetic basis.
      These chromosome aberrations may have diagnostic utility as markers of prostate
      cancer progression.

PMID- 7529135
TI  - Pathogenesis of ascites tumor growth: angiogenesis, vascular remodeling, and
      stroma formation in the peritoneal lining.
AB  - In the accompanying papers, we demonstrated that two murine ascites tumors (MOT
      and TA3/St) induced peritoneal lining blood vessels to become hyperpermeable to
      plasma proteins, leading to extravasation of fibrinogen and its clotting to cross
      linked fibrin in peritoneal lining tissues (peritoneal wall, mesentery, and
      diaphragm). In solid tumors, vascular hyperpermeability and fibrin deposition
      lead to the generation of vascularized connective tissue. In order to determine
      whether fibrin had similar consequences in ascites tumors, the vasculature and
      stroma of peritoneal lining tissues were analyzed at successive intervals after
      i.p. tumor cell injection. In both MOT and TA3/St ascites tumors, the size and
      number of peritoneal lining microvessels increased significantly by 5-8 days.
      Subsequently, peritoneal lining vessels increased in cross-sectional area by as
      much as 15-fold and peritoneal vascular frequency increased by up to 11-fold.
      Incorporation of [3H]thymidine by mesenteric blood vessels was negligible in
      control animals but came to involve 20 and 40% of endothelial cells lining
      mesenteric vessels in MOT and TA3/St ascites tumor-bearing mice, respectively.
      After an early dramatic increase in cross-sectional area, peritoneal lining
      microvessels subsequently underwent a novel form of remodeling to smaller average
      size as the result of transvascular bridging by endothelial cell cytoplasmic
      processes. Thus, both of the ascites tumors studied here induced angiogenesis and
      stroma similar to that elicited when these same tumors were grown in solid form.
      However, stroma developed more slowly in ascites than in solid tumors and was
      entirely confined to a compartment (peritoneal lining tissues) that was distinct
      from that (peritoneal cavity) containing the majority of tumor cells and ascites
      fluid. These findings are consistent with the hypothesis that vascular
      hyperpermeability, induced in both solid and ascites tumors by tumor cell
      secreted vascular permeability factor, is a common early step in tumor
      angiogenesis, resulting in fibrinogen extravasation, fibrin deposition, and
      likely other alterations of the extracellular matrix that together stimulate new
      vessel and fibroblast ingrowth.

PMID- 7529137
TI  - Involvement of the very late antigen 4 integrin on melanoma in interleukin 1
      augmented experimental metastases.
AB  - We have previously reported that treatment with interleukin 1 (IL-1) induced the
      augmentation of lung tumor colonies by a human melanoma in nude mice. Here we
      have investigated the involvement of the alpha 4 beta 1 integrin, the very late
      antigen 4 (VLA-4) in this augmentation. A375M melanoma cells expressed high
      levels of VLA-4 and preferentially adhered to a surface coated with vascular cell
      adhesion molecule 1 (VCAM-1), the ligand for VLA-4 on activated endothelial
      cells. This adhesion was inhibited by treating tumor cells with saturating
      concentrations of mAb to VLA-4. The production of lung colonies was significantly
      enhanced in nude mice given an injection of IL-1 before A375M melanoma cells.
      Immunoperoxidase staining showed that VCAM-1 could be expressed on lung vascular
      endothelium of mice in response to IL-1. Pretreatment of melanoma cells with a
      mAb to VLA-4 completely abrogated the IL-1-induced augmentation of lung colonies.
      Using two metastatic melanoma clones (clones 2/4 and 2/60) that expressed
      different levels of VLA-4, we found that only VLA-4-bearing cells adhered to a
      VCAM-1-coated surface and formed enhanced numbers of lung colonies in IL-1
      treated nude mice. This augmentation was inhibited by pretreating the tumor cells
      with anti-VLA-4 mAb. These results demonstrate, in vivo, the functional
      involvement of VLA-4 on melanoma cells in IL-1-mediated lung colony augmentation,
      most probably involving the interaction of tumor cells with VCAM-1 on activated
      endothelial cells.

PMID- 7529136
TI  - Progression of hormone-dependent adenocarcinoma cells to hormone-independent
      spindle carcinoma cells in vitro in a clonal spontaneous rat mammary tumor cell
      line.
AB  - A hormone-dependent, clonal carcinoma cell line, designated RM22-F5, was derived
      from a malignant mammary mixed tumor spontaneously arising in an outbred old
      female Wistar rat. These cells expressed keratin and desmosomal protein and
      formed epithelial monolayers in a growth factor and hormone-supplemented medium
      (LHC-8) containing 10% fetal bovine serum (E-type cells). Cells subcultured for 6
      to 8 passages in RPMI 1640 medium containing 10% fetal bovine serum without
      supplements appeared to be fibroblastic and expressed vimentin (F-type cells).
      The shift to a fibroblast-like morphology was associated with a more malignant
      phenotype which included rapid, hormone-independent growth and invasive sarcoma
      like character in nude mice. F-type cells were no longer able to express their
      original epithelial phenotype in LHC-8 medium. Cytogenetic analysis revealed that
      both E- and F-type cells had essentially the same karyotype. Analysis of PCR
      amplified DNA further demonstrated a point mutation of the H-ras-1 gene at codon
      12 and loss of the normal H-ras-1 allele in both cell types. Genetic tagging of E
      type cells with the neomycin-resistance gene resulted in the generation of F-type
      cells with neomycin resistance in RPMI 1640 medium, suggesting that F-type cells
      are a malignant variant of E-type cells arising during in vitro culture. Somatic
      cell fusion between E- and F-type cells revealed that with most hybrid clones
      tested, the fibroblast-like phenotype was greatly suppressed. These results
      suggest that an irreversible phenotypic transition, representative of tumor
      progression from hormone-dependent adenocarcinoma to more malignant hormone
      independent spindle carcinoma cells, is a recessive event and may involve loss of
      a suppressor function.

PMID- 7529138
TI  - Hyaluronan on the surface of tumor cells is correlated with metastatic behavior.
AB  - In the present study, we examined the metastatic potential of tumor cells
      expressing different levels of cell surface hyaluronan. We used flow cytometry to
      isolate subsets of the B16-F1 mouse melanoma cell line that expressed either high
      (HA-H) or low (HA-L) amounts of hyaluronan on their surfaces. These two subsets
      of cells showed a 32-fold difference in the amount of cell surface hyaluronan,
      due to its rate of synthesis. However, these cell lines did not differ from each
      other with regard to their in vitro growth rates, susceptibility to natural
      killer-mediated cytotoxicity, or the expression of the cell surface proteins
      CD44, ICAM-1, and GMP-140. When these cells were injected s.c., they both formed
      s.c. tumors of approximately the same size. However, when injected into the tail
      vein of mice, the HA-H cells formed a greater number of nodules in the lungs and
      caused a faster rate of mortality than the HA-L cells. The presence of hyaluronan
      did enhance the interaction of the HA-H cells with cultured endothelial cells
      that expressed CD44. Thus, it is possible that enhanced interactions between
      hyaluronan and CD44 promoted the formation of tumor embolisms which, in turn,
      increased the chances that the tumor cells would be trapped in the lungs. Taken
      together, these results suggest that hyaluronan may play a critical role in the
      process of tumor metastasis.

PMID- 7529139
TI  - Promyelocytic leukemia-specific PML-retinoic acid alpha receptor fusion protein
      interferes with erythroid differentiation of human erythroleukemia K562 cells.
AB  - Acute promyelocytic leukemia (APL) is characterized by a t(15;17) chromosomal
      translocation with breakpoints within the retinoic acid alpha receptor (RAR
      alpha) gene on 17 and the PML gene, which encodes a putative transcription
      factor, on 15. A PML-RAR alpha fusion protein is formed as a consequence of the
      translocation. We show here that expression of the PML-RAR alpha protein in K562
      erythroleukemia cells results in a reduced expression of erythroid
      differentiation markers and a reduced sensitivity to the erythroid
      differentiative action of heme. Overexpression of RAR alpha, but not of PML,
      elicited a similar inhibition of K562 erythroid differentiation. These findings
      indicate that overexpression of either RAR alpha or PML/RAR alpha interferes with
      erythroid differentiation and support the hypothesis that RAR alpha is involved
      in the regulation of normal hematopoiesis and alteration of the RAR alpha
      signaling by PML/RAR alpha is implicated in the promyelocytic leukemogenesis.

PMID- 7529140
TI  - The fourth immunoglobulin domain of the stem cell factor receptor couples ligand
      binding to signal transduction.
AB  - Receptor dimerization is ubiquitous to the action of all receptor tyrosine
      kinases, and in the case of dimeric ligands, such as the stem cell factor (SCF),
      it was attributed to ligand bivalency. However, by using a dimerization
      inhibitory monoclonal antibody to the SCF receptor, we confined a putative
      dimerization site to the nonstandard fourth immunoglobulin-like domain of the
      receptor. Deletion of this domain not only abolished ligand-induced dimerization
      and completely inhibited signal transduction, but also provided insights into the
      mechanism of the coupling of ligand binding to dimer formation. These results
      identify an intrinsic receptor dimerization site and suggest that similar sites
      may exist in other receptors.

PMID- 7529141
TI  - Dissecting RNA-protein interactions: RNA-RNA recognition by Rop.
AB  - The ColE1 plasmid of E. coli encodes a small RNA-binding protein, Rop, which is
      involved in the regulation of plasmid copy number. Rop, a 4-helix bundle protein,
      facilitates sense-antisense RNA pairing by binding to the transiently formed
      hairpin pairs of RNA I and the complementary RNA II. We have identified the
      residues of Rop that are involved in RNA recognition. The residues form a narrow
      stripe down one face of the bundle and are symmetrically arranged, with
      recognition centered about two phenylalanine residues. Our results suggest that
      these phenylalanine residues interact with the loop region of the hairpin pair,
      with additional interactions between eight polar residues and the phosphate
      backbone. By modifying the identity of residue 14, we have created a variant of
      Rop that displays altered RNA binding specificity. The results of our studies
      allow us to present a detailed picture of RNA-protein recognition in a novel
      model system.

PMID- 7529142
TI  - Ontogeny of nitric oxide synthase in the lumbosacral spinal cord of the neonatal
      rat.
AB  - The present experiments were performed to determine the temporal pattern of
      expression of nitric oxide synthase (NOS) immunoreactivity in cells and fibers in
      the lumbosacral spinal cord during early postnatal development and to examine the
      relationship between NADPH-diaphorase (NADPH-d) activity and NOS-immunoreactivity
      (IR). At postnatal days 0-1 and 4-5, NADPH-d and NOS-IR were detected in L6-S1
      segments of the spinal cord in cells and fibers in the region of the sacral
      parasympathetic nucleus (SPN), dorsal commissure and around the central canal but
      were absent in the superficial layers of the dorsal horn. Fiber staining on the
      lateral edge of the dorsal horn (the lateral collateral pathway, LCP) in a region
      containing primary afferent projections from the pelvic viscera and in a fiber
      tract in the dorsolateral funiculus was also not detectable. At days 4-5 some
      stained cells were detected in the deeper laminae of the dorsal horn. At
      postnatal days 10-12 and 20-22, cells in the region of the SPN, around the
      central canal and in the superficial laminae of the dorsal horn exhibited NADPH-d
      and NOS-IR. NADPH-d and NOS-IR fiber staining in the superficial laminae of the
      dorsal horn and the dorsolateral funiculus was observed at postnatal days 10-12
      and increased in staining intensity by postnatal days 20-22. NADPH-d fiber
      staining in the LCP was not prominent at postnatal days 10-12; however, prominent
      fiber staining at this site did occur by postnatal days 20-22 and in adult
      animals. In postnatal days 20-22 and in adult animals NADPH-d activity and NOS-IR
      had a similar distribution except in the LCP where NADPH-d stained fibers did not
      exhibit NOS-IR. These data indicate that NADPH-d and NOS-IR in the spinal cord
      exhibit marked changes during the early postnatal development. The changes in
      afferent projections in the LCP may be related to maturation of visceral reflex
      pathways including micturition.

PMID- 7529144
TI  - Multiple forms of prostate-specific antigen in serum measured differently in
      equimolar- and skewed-response assays.

PMID- 7529143
TI  - Expression of mouse brain soluble guanylyl cyclase and NO synthase during
      ontogeny.
AB  - The spatial and temporal distribution of soluble guanylyl cyclase and nitric
      oxide synthase mRNA was determined during embryonic and postnatal development of
      the mouse brain. This was achieved by in situ hybridization of specific probes
      for soluble beta 1 guanylyl cyclase subunit and nitric oxide synthase mRNA on
      mouse brain sections at late fetal development (19-day embryo) and different
      stages of postnatal development (3, 7, 15 days, and adult). In the embryo,
      soluble guanylyl cyclase transcripts are weakly expressed in the central nervous
      system. Following birth their expression increases in the striatum and neocortex,
      and they are widely distributed in the adult brain (layer II and V-VI of the
      cortex, olfactory bulb, striatum, Purkinje cell layer of the cerebellum). In
      contrast, nitric oxide synthase mRNA was expressed in several embryonic
      structures of the brain (different layers of the cortical neuroepithelium,
      colliculi neuroepithelium, pons), and markedly reduced at early postnatal stage,
      except in the accessory olfactory bulb and pediculopontine nuclei. Nitric oxide
      synthase transcripts progressively appear, within two weeks following birth, in
      the striatum and the cerebral cortex but they were specifically confined to
      isolated cells. During this period, this mRNA also increased in hippocampus, in
      discrete nuclei (hypothalamus, pontine) and in the molecular layer of the
      cerebellum. The situation in the adult was similar to the one observed at 15
      days. These results show a general lack of regional colocalization of soluble
      guanylyl cyclase and NOS mRNA during ontogeny, thus suggesting an independent
      regulation of the related genes.

PMID- 7529145
TI  - Rapid, automated quantification of total human chorionic gonadotropin in serum by
      a chemiluminescent enzyme immunometric assay.
AB  - Total human chorionic gonadotropin (hCG-hCG beta) in serum was assayed with the
      immulite system, a fully automated random-access immunoassay analyzer that has a
      unique centrifugal procedure for solid-phase washing and a chemiluminescent
      detection system. The broad range of the hCG calibration curve (up to 5000 IU/L)
      is achieved by using a small serum sample size (5 microL), which provides
      sufficient volume for low-end sensitivity and prevents the possible high-dose
      hook effect in the working range of the assay. Within-run imprecision (CV) ranged
      from 3.9% to 5.9% for hCG between 10.5 and 2908 IU/L. Between-run imprecision
      ranged from 8.8% to 12.7% for hCG mean concentrations from 11.4 to 88.4 IU/L. The
      antibodies used in the immulite hCG assay system gave little or no interferences
      when high amounts of follitropin, lutropin, and thyrotropin were added. A
      complete recognition of the free beta-subunit of hCG was obtained (+/- 180%). In
      sera from women with molar pregnancies, we observed no high-dose hook effect at
      hCG concentrations up to 3000 kIU/L. The broad range of hCG concentrations
      encountered throughout normal pregnancy (up to 200 kIU/L) requires an extended
      working range to avoid high dilutions. In early pregnancy, accuracy in the range
      of 1000-5000 IU/L is enhanced by avoiding dilutions.

PMID- 7529147
TI  - Nonprostatic sources of prostate-specific antigen: a steroid hormone-dependent
      phenomenon?

PMID- 7529146
TI  - Prostate-specific antigen in milk of lactating women.
AB  - Prostate-specific antigen (PSA) is believed to be a highly specific marker for
      normal and cancerous prostatic tissue. We recently found that 30-40% of breast
      tumors produce PSA. Other data from our group suggest that normal breast can also
      produce PSA under conditions of stimulation by steroid hormones. In addition, we
      detected PSA in amniotic fluid. Here we report the presence of PSA in breast milk
      of lactating women. PSA concentrations in breast milk were quite variable,
      ranging from < 0.01 microgram/L in 4 of 38 milks to 350 micrograms/L; the median
      was 0.47 microgram/L. PSA concentration in breast milk was not correlated with
      mother's age or the sex of the newborn. It did tend to decrease with increasing
      time postdelivery, but was still detectable 2 weeks postdelivery. PSA in milk was
      equally measurable by a highly sensitive PSA assay based on time-resolved
      fluorometry and by the IMx automated PSA method. As confirmed by Western blot
      analysis, PSA in milk was present predominantly in its 33-kDa form; the PSA-alpha
      1-antichymotrypsin complex (100 kDa) was also present but its concentration was <
      25% of total PSA. We conclude that the female breast can produce PSA and that PSA
      is secreted into the milk during lactation; however, the biological role of PSA
      in milk is unknown. These and other data presented by our group suggest that PSA,
      a serine protease, may play a role in control of growth in mammary and other
      tissues through regulation of growth factors, cytokines, and growth-factor
      binding proteins.

PMID- 7529148
TI  - IL-4 induces neutrophilic maturation of HL-60 cells and activation of human
      peripheral blood neutrophils.
AB  - IL-4 is a T-helper cell derived cytokine that has effects on myelomonocytic cell
      maturation and activation. We have studied the effect of IL-4 on neutrophilic
      maturation using the cell line HL-60 and found that it has a profound effect on
      the maturation and activation of the cell line. The treatment of HL-60 cells with
      recombinant hu IL-4 (0.15 to 15.0 ng/ml) induced a shift in the percentage of HL
      60 cells staining positive for chloroacetate esterase enzyme activity (indicating
      commitment to the neutrophilic lineage). IL-4 increased surface expression of the
      neutrophil-lineage antigen WEM G11, the complement receptors CR3 (CD11b) and CR1
      (CD35), but not for the monocyte differentiation antigen CD14. IL-4 treated HL-60
      cells demonstrated enhanced Fc- and complement-mediated phagocytic capacity and
      increased hexose-monophosphate shunt activity. In addition, IL-4 was capable of
      sustaining the neutrophil maturation of HL-60 cells that had been pre-treated for
      24 h with DMSO. To investigate the effect of IL-4 on the mature neutrophil, we
      studied freshly isolated and rested human peripheral blood neutrophils. In the
      absence of other stimuli, neutrophils were induced by IL-4 to have significantly
      elevated phagocytic responses. The response was specific since treatment with
      anti-human IL-4 abolished phagocytic stimulation. Finally, IL-4 treatment also
      stimulated resting neutrophils to migrate toward zymosan-activated serum (ZAS)
      and human IL-5. The results demonstrate that IL-4 is a potent maturation factor
      for myelocytes to become neutrophils and that IL-4 can stimulate resting mature
      neutrophils.

PMID- 7529149
TI  - Autoantibodies in human anti-Ro sera specifically recognize deproteinized hY5 Ro
      RNA.
AB  - We report the existence of a novel autoantibody specificity linked to anti-Ro
      antibodies. Sera from two patients with anti-Ro ribonucleoprotein (RNP)
      antibodies also contained antibodies that immunoprecipitated specifically either
      the deproteinized RNA component of the RohY5 RNP particle, or intact in vitro
      transcribed hY5 RNA. No serum recognized specifically the other hY RNAs. A mutant
      hY5 RNA with additional nucleotides (nt) at both extremities was not
      immunoprecipitated, possibly because of altered secondary structure. Following
      digestion of hY5 RNA with ribonuclease T1, the smallest immunoprecipitable RNA
      fragments were 27 and 31 nt long, and respectively mapped to the 5' and 3' ends
      of hY5 RNA, excluding the La-binding region. Base pairing between the 27 and 31
      nt long fragments was required for recognition by antibodies. Our data indicate
      that the epitope bound by anti-hY5 RNA antibodies is conformational. We have
      previously reported that most anti-Ro sera contain a population of antibodies
      specific for the RohY5 RNP. Since antibodies to the deproteinized hY RNAs within
      anti-Ro sera are also restricted to anti-hY5 RNA, a direct role for the human
      specific RohY5 particles in the immunization process leading to the production of
      anti-Ro antibodies is suggested.

PMID- 7529151
TI  - Autoantibodies to the RoRNP particles.

PMID- 7529150
TI  - Autoantibodies to histone, DNA and nucleosome antigens in canine systemic lupus
      erythematosus.
AB  - Dogs can develop systemic lupus erythematosus syndromes that are clinically
      similar to those seen in humans. In contrast, previous observations suggest
      differences in their autoantibody reactivity patterns against histones and DNA
      which are components of the nucleosome in chromatin. The objective of this study
      was to assess comprehensively the levels of autoantibodies against histone, DNA
      and nucleosome antigens in a population of lupus dogs. The specificities of
      antibodies in lupus and control dog sera were determined using IgM- and IgG
      specific reagents in an ELISA against a variety of chromatin antigens. When
      compared with control sera, IgG antibodies to individual histones H1, H2A, H3 and
      H4 were significantly higher in the lupus group. In contrast, we did not detect
      IgG antibodies specific for H2B, H2A-H2B, DNA, H2A-H2B-DNA or nucleosome in lupus
      dogs. There was no significant increase in any of the IgM specificities tested.
      Therefore, the reactivity pattern to nucleosome antigens in canine lupus is
      restricted to IgG antibodies against individual histones H1, H2A, H3 and H4. This
      stands in contrast with human and murine lupus, where autoantibodies are directed
      against a wide variety of nucleosomal determinants, suggesting that unique
      mechanisms lead to the expansion of anti-histone antibody clones in canine lupus.
      The high incidence of glomerulonephritis in dog lupus suggests that anti-DNA
      antibodies are not required for the development of this complication, whereas IgG
      anti-histone antibodies may be relevant to its pathogenesis.

PMID- 7529153
TI  - The development of cocaine-exposed children.

PMID- 7529152
TI  - Effect of inhibition of nitric oxide synthase and guanylate cyclase on
      hydralazine-induced vasodilatation of the human fetal placental circulation.
AB  - 1. The vasodilator effects of hydralazine in vitro, using the Krebs' perfused
      human placental lobule was studied. Single placental lobules were bilaterally
      perfused (maternal and fetal sides 5 mL/min each, 95% O2, 5% CO2, 37 degrees C)
      and changes in fetal arterial pressure (FAP) and venous outflow (VO) were
      recorded. 2. Submaximal vasoconstriction was induced by KCl (20-50 mmol/L), which
      increased basal FAP from 22.8 +/- 1.7 to 91.3 +/- 3.9 mmHg (n = 9, P < 0.001),
      and decreased VO from 4.1 +/- 0.6 to 0.2 +/- 0.1 mL/min (n = 6, P < 0.01). 3.
      Hydralazine caused vasodilatation (IC50 1.9 mmol/L, n = 9) and increased VO in
      the presence of KCl-induced vasoconstriction. 4. Infusion of N omega-nitro-L
      arginine (100 mumol/L) to block nitric oxide synthase caused the basal FAP to
      increase from 30.9 +/- 5.9 to 47.4 +/- 6.7 (n = 6, P < 0.05) and significantly
      potentiated hydralazine-induced vasodilatation (n = 7, P < 0.05). 5. The soluble
      guanylate cyclase inhibitor LY 83583 (6-anilino-5,8-quinolinedione) (1 mumol/L)
      significantly antagonized the vasodilatation produced by hydralazine (n = 5, P <
      0.05). 6. Thus, Hydralazine appears to activate guanylate cyclase, leading to
      increased cyclic GMP in fetal arterial vascular smooth muscle to cause
      vasorelaxation. No evidence was obtained to suggest that hydralazine exerted its
      action by either releasing nitric oxide from endothelial cells in the placenta or
      acting as a nitric oxide donor.

PMID- 7529154
TI  - Impairment in gas exchange after granulocyte colony stimulating factor (G-CSF) in
      a patient with the adult respiratory distress syndrome.
AB  - We describe the previously unreported finding of reproducible arterial d
      desaturation after successive injections of granulocyte colony stimulating factor
      in a orthotopic liver transplant recipient with the adult respiratory distress
      syndrome and antibiotic-induced neutropenia.

PMID- 7529155
TI  - Artifactual staining of monoclonal antibodies in two-color combinations is due to
      an immunoglobulin in the serum and plasma.
AB  - Two-color whole blood lysis is the assay of choice for lymphocyte
      immunophenotyping because of the additional information it provides. Recently,
      artifactual double-staining of some specimens has been observed with this assay.
      In these cases, the samples appear to be uncompensated for spectral overlap or to
      inappropriately coexpress two antigens simultaneously. This artifact can result
      in the apparent coexpression of CD4 and CD8 (observed in lymphoblastic processes)
      or of CD5 and CD20 (characteristic of chronic lymphocytic leukemia) in normal
      persons, leading to an erroneous diagnosis. Using plasma, serum, or
      immunoglobulin preparations from donors who exhibit this artifact we sought to
      determine 1) the source of the artifact and 2) ways to overcome it. This staining
      is apparently due to an immunoglobulin in the donors' serum and plasma which does
      not have specific reactivity with mouse immunoglobulin. Washing whole blood
      samples or blocking with mouse immunoglobulin is a convenient way of avoiding
      this artifact.

PMID- 7529156
TI  - Evaluation of growth and energy storage as biological markers of DDT exposure in
      sailfin mollies.
AB  - Direct and indirect measures of growth and energy storage were evaluated as
      indicators of subchronic 1,1,1-trichloro-2-(o-chlorophenyl)-2-(p
      chlorophenyl)ethane (o,p'-DDT) exposure in juvenile sailfin mollies (Poecilia
      latipinna). Three-day-old mollies were exposed to 0, 1, 10, 25, 50, 75, and 100
      micrograms/liter o,p'-DDT for 21 days. Tissue residues, percentage weight gain,
      RNA and DNA content, RNA:DNA ratio, percentage total lipid, percentage
      triglyceride, percentage total protein, and triglyceride:total lipid ratio were
      measured following exposure. Mortality was concentration and time dependent, with
      100% mortality at 75 and 100 micrograms/liter. Among controls and remaining
      treatments, tissue residues (0.50 to 363 ng/mg dry wt), percentage weight gain
      (116 to 596%), percentage total lipid (2.84 to 4.33%), and percentage
      triglyceride (1.01 to 3.22%) were significantly different. Tissue residues were
      positively correlated with concentration, while percentage weight gain,
      percentage lipid, percentage triglyceride, and triglyceride:total lipid ratio
      were negatively correlated with concentration. Direct measures are likely to
      remain the method of choice for evaluating effects of toxicants on growth in
      laboratory exposures because of their relative simplicity and reliability.
      However, indirect measures of energy storage, such as triglyceride:total lipid
      ratio, rather than direct measures of various lipid fractions may be more
      reliable indicators of the energetic cost of toxicant stress.

PMID- 7529158
TI  - Biodegradation and toxicity to fish of di-long-chain tertiary amine salt
      containing ester and amide bonds.
AB  - Biodegradability of N-(3-alkanoylaminopropyl)-N-(2-alkanoyloxyethyl)-N-
      methylammonium chloride (EAA) was investigated. Biodegradabilities by biochemical
      oxygen demand (BOD) and dissolved organic carbon (DOC) after 28 days were 79 and
      91%, respectively, and almost the same amount of ammonium ion as the theoretical
      value was detected using a modified MITI test (I) (OECD guidelines, 301C). In the
      test with activated sludge obtained from a municipal sewage treatment plant,
      biodegradabilities by BOD and DOC after 35 days were 87 and 98%, respectively,
      and the 1H-NMR analysis of the tested solution which was done separately under
      similar conditions indicated the rise and fall of two biodegradation
      intermediates. Therefore, EEA was considered to be a readily and ultimately
      biodegradable compound. Besides, the 96-hr LC50 value in red killifish (Oryzias
      latipes) of EAA was 66 mg/liter. More than 1000 mg/liter was of biodegradation
      intermediates rapidly made by biodegradation of EAA. These results reveal that
      EAA has sufficient environmental compatibility.

PMID- 7529157
TI  - The ecotoxicological significance of cadmium intake and residues in terrestrial
      small mammals.
AB  - Little is known about the ecotoxicological hazard of cadmium to wild small
      mammals. This paper reviewed laboratory and field studies to determine: (i)
      intake and residue lowest-observable-adverse-effect-levels (LOAELs) for the
      ecologically important parameters of reproduction and development; (ii) whether
      these LOAELs are exceeded by wild small mammals on contaminated habitats and what
      adverse effects result; and (iii) which species may be at most risk from cadmium.
      The intake LOAEL in laboratory rodents was 3.5-7.5 mg kg-1 body wt day-1 and the
      residue LOAEL, based on cellular damage in the kidney, was a renal cadmium
      concentration of 105 mg kg-1 dry wt. On contaminated habitats, these LOAELs are
      exceeded by common shrews Sorex araneus but not by wild rodents. However, there
      is little evidence of adverse cadmium-mediated effects in common shrews and this
      species may be tolerant to cadmium exposure. Large cadmium concentrations in body
      organs may simply reflect an ability to store cadmium in a nontoxic,
      metallothionein-bound state. In contrast, studies suggest that microtine voles
      may be sensitive to cadmium and, despite their relatively low cadmium intake and
      accumulated residues, may suffer adverse effects. The need to establish dose
      residue-effect relationships for intakes and residues which are appropriate for
      wild species and also based on ecologically important parameters is discussed.

PMID- 7529159
TI  - Lead exposure in students in Mexico City.
AB  - The present study was done between 1989 and 1991 and performed on 263 children 7
      to 9 years of age who lived in Mexico City. The goal was to determine the
      association between risk factors entering the body through the respiratory or
      digestive path and lead concentration in deciduous teeth. Exposure to risk
      factors was surveyed through a questionnaire; lead was determined by atomic
      absorption spectrophotometry with a graphite oven and reported in microgram Pb/g
      tooth. Statistical significance was found for the habit of sucking toys OR 4.98
      (IC 95% 1.23-28.67), the use of glazed earthenware utensils for the preparation
      and serving of food and drinks OR 2.47 (IC 0.80-8.47), and the ingestion of
      tinned food, particularly juices OR 3.31 (IC 1.03-12.50). No positive results
      were found for risk factors involving the respiratory path. A possible
      explanation for these results is a different risk level for each of the two paths
      of access.

PMID- 7529160
TI  - Evaluation of a rodent peroxisome proliferator in two species of freshwater fish:
      rainbow trout (Onchorynchus mykiss) and Japanese medaka (Oryzias latipes)
AB  - Rainbow trout (Onchorynchus mykiss) and Japanese medaka (Oryzias latipes) were
      exposed to the hypolipidemic drug gemfibrozil, a known rodent peroxisome
      proliferator. Trout were injected (i.p.) daily for 2 weeks at doses of 0, 46, 87,
      or 152 mg/kg/day. Medaka were exposed to the nominal concentrations of 0, 1.25,
      2.5, or 5 ppm in water for 2 weeks in a static-renewal system. Peroxisome
      proliferation was assessed by measuring fatty acyl-CoA oxidase (FAO) activity,
      peroxisomal bifunctional enzyme (PBE) quantity, and changes in liver-to-body
      weight ratios (LWR). Results indicate that a mild peroxisome proliferative
      response was observed in rainbow trout (significant increases in FAO activity at
      all dose levels and in LWR at the highest dose level). Medaka demonstrated a
      significant increase in PBE at the highest dose level, while nonsignificant
      increases in FAO activity were observed at the mid- and high-dose levels.

PMID- 7529161
TI  - A genetic and morphometric comparison of Helisoma trivolvis and Gambusia
      holbrooki from clean and contaminated habitats.
AB  - Genetic and morphometric data from freshwater snail (Helisoma trivolvis) and
      mosquitofish (Gambusia holbrooki) populations from a relatively clean and a
      severely contaminated habitat were compared. Within the clean habitat, snail
      genetic patterns may have been more influenced than those of mosquitofish by site
      specific selection because of the lesser likelihood of gene flow among snail
      subpopulations. Distinct genetic patterns within the contaminated habitat,
      combined with data from other published work, suggest that selection for tolerant
      genotypes may have occurred in both species. Body size in both species was
      associated with glucosephosphate isomerase allozyme genotype. In snails, apparent
      selection for a particular allele in the contaminated habitat may be related to
      its contaminant tolerance and body-size plasticity. In mosquitofish, a particular
      genotype associated with small body size appears to have been favored in the
      contaminated environment.

PMID- 7529162
TI  - Cadmium toxicity to rainbow trout Oncorhynchus mykiss Walbaum and brown trout
      Salmo trutta L. over extended exposure periods.
AB  - The toxicity of cadmium in water is well known, but there have been few reports
      on the long-term effects of this metal on fish at concentrations near the
      European inland water standard of 5 micrograms Cd liter-1. This paper describes
      experiments in which adult rainbow trout Oncorhynchus mykiss and brown trout
      Salmo trutta were exposed to cadmium concentrations near water quality standard
      levels for periods of up to 90 weeks. The survival and growth of these fish were
      assessed, and sperm and eggs were stripped from them to conduct early-life-stage
      tests. Continuous exposure of rainbow trout adults to cadmium concentrations of
      up to 5.5 micrograms Cd liter-1 did not affect their survival or growth. However,
      eggs obtained from rainbow trout exposed to 1.8 and 3.4 micrograms Cd liter-1
      failed to develop to the fry stage. Oogenesis appeared to be delayed in brown
      trout exposed to 9.3 and 29.1 micrograms Cd liter-1, but the eggs and fry that
      were produced developed normally after fertilization. Adult brown trout suffered
      considerable mortality in the 29.1 micrograms Cd liter-1 treatment, with a median
      period of survival of 54 weeks.

PMID- 7529163
TI  - Mass spectral study of chlorofluorocarbons (CFCs) and potential alternatives
      (HCFCs and HFCs).
AB  - Owing to high ozone depletion potential of the chlorofluorocarbons (CFCs), the
      production of such substances has been regulated worldwide by the Montreal
      Protocol in 1987. There is an urgent need to find other suitable products to
      replace them and hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs)
      are considered to be the most probable candidates as CFC alternatives. The HCFCs
      and HFCs are more susceptible to decomposition during use than CFCs because they
      contain hydrogen. Toxicological data on these alternative fluorocarbons are being
      developed. A systematic investigation of these compounds has been undertaken to
      establish the fragmentation patterns. Electron impact mass spectra are reported
      for HCFCs and HFCs. Fragmentation mechanisms are presented and discussed on the
      basis of variable energy (11 to 30 eV) spectra. At low ionization energy, it is
      possible to describe an order of fragmentation for each compound. This may lead
      to the possibility of classifying them according to characteristic behaviors.

PMID- 7529165
TI  - Influence of different factors on the adsorption of carbofuran (2, 3-dihydro-2,2
      dimethyl-7-benzofuranyl-N-methyl carbamate) on soils.
AB  - The effects of exchangeable cations (H+ and Na+), autoclaving, organic matter,
      cationic and anionic surfactants, and temperature on the adsorption of carbofuran
      on two different types of soils were studied. The adsorption isotherms for all
      effects/treatments were in close agreement with the Freundlich equation and
      yielded S-shaped isotherms. The amount of carbofuran adsorbed in all cases was
      higher in Jhansi red loam soil than in Pilibhit sandy loam soil and was related
      to organic matter content, clay content, CaCO3 content, surface area, and cation
      exchange capacity of the soils. The adsorption on soils from both sites follows
      the order H soil-->Na soil-->natural soil at 25 degrees C-->autoclaved soil-
      >soil from which organic matter had been removed-->cationic surfactant-->anionic
      surfactant-->natural soil at 50 degrees C and was in accordance with Freundlich
      constant K values and distribution coefficient Kd values. The adsorptive capacity
      of carbofuran for organic matter and clay content for both the Jhansi and the
      Pilibhit soils was also evaluated by calculating Kom and Kc values, and it was
      found that the carbofuran adsorption was better correlated with clay content than
      with organic matter content of soils. On the basis of adsorption isotherms,
      various thermodynamic parameters such as the thermodynamic equilibrium constant
      Ko, standard free energy (delta G zero) changes standard ethalpy (delta H zero)
      changes, and standard entropy (delta S zero) changes have been calculated in
      order to predict the nature of isotherms.

PMID- 7529166
TI  - Effects of 3,4-dichloroaniline on the growth of two freshwater macroinvertebrates
      in a stream mesocosm.
AB  - The growth of the freshwater macroinvertebrates Gammarus pulex (L.) and
      Chironomus riparius Meigen exposed to 3,4-dichloroaniline in chambers within
      stream mesocosms was determined. DCA significantly affected the growth of neonate
      G. pulex and third instar C. riparius over 25 and 12 days, respectively. The no
      observed-effect concentrations (NOECs) obtained in the tests were 0.08 mg DCA
      liter-1 (G. pulex) and 0.76 mg DCA liter-1 (C. riparius) and these are compared
      to toxicity data from other investigations. Inclusion of single-species bioassays
      in mesocosm studies provides complementary information on toxicant effects and
      indicates the suitability of the results of such tests (which may be routinely
      performed under laboratory conditions) for protecting particular ecosystems.

PMID- 7529167
TI  - Effect of mixtures of chlorophenols, surfactants, and aniline on growth of
      Pseudomonas fluorescens.
AB  - Industrial wastewater often contains a mixture of chemical substances and
      knowledge of joint action of toxicants is therefore important when the toxicity
      of an effluent is evaluated or reduction of the toxicity is needed. In this
      study, the joint action of three pairs of toxicants, selected on the basis of
      their expected different modes of toxic actions, was tested for inhibition of the
      growth of the bacteria Pseudomonas fluorescens: pentachlorophenol and aniline,
      the surfactants nonylphenolethoxylate and tetrapropylenebenzenesulfonate, and
      pentachlorophenol and 2, 4-dichlorophenol. The joint effect of pentachlorophenol
      and aniline did not differ significantly from additivity, whereas less than
      additive responses were observed for mixtures of nonylphenolethoxylate and
      tetrapropylenbenzenesulfonate. A more than additive response was observed for
      mixtures of pentachlorophenol and 2,4-dichlorophenol at some concentration
      levels, while at others additive responses were found. It was concluded that
      joint actions other than additivity may occur between commonly known toxic
      substances, and that the modes of toxic action of the substances studied can
      explain the different types of joint action observed in this study. Further, test
      strategy followed proved useful in the evaluation of the joint toxicity of binary
      mixtures.

PMID- 7529164
TI  - Adsorption and mobility of acephate in soils.
AB  - The influence of soil properties on the adsorption and mobility of acephate (O, S
      dimethylacetylphosphoroamidothioate) was studied. The Freundlich adsorption
      constant (K) and the distribution coefficient (Kd) were found to be highly
      correlated (P < 0.001) with the silt + clay content of the soil, both for the
      studied soils as a whole and for those with organic matter contents below 2%. The
      mobility of acephate as determined by thin-layer chromatography (saturated flow
      conditions) was found to be Rf = 1 for all soils except the three with a high
      silt + clay content, whose Rf was smaller than unity. A study of the acephate
      mobility in soil-packed columns under unsaturated flow conditions revealed that
      the highest proportion of the insecticide was retained at the top of the columns;
      also, the insecticide distribution in the columns and the overall amounts
      retained and leached were related to the silt+clay content of the soils.

PMID- 7529168
TI  - Cadmium-induced mRNA encoding a nonmetallothionein 33-kDa protein in Enchytraeus
      buchholzi (Oligochaeta).
AB  - Enchytraeus buchholzi (Oligochaeta) were exposed to various concentrations of
      CdCl2 in agar and aqueous solution. The Cd uptake was determined by atomic
      absorption spectroscopy as well as Cd effects on survival, reproduction, and mRNA
      synthesis by in vitro translation of total RNA in a rabbit reticulocyte lysate
      system. Although Cd was rapidly accumulated by the worms, any acute toxic Cd
      effects at concentrations below 4 mg Cd/liter were not detectable. However, such
      subtoxic Cd concentrations caused the induction of an mRNA species coding for a
      nonmetallothionein 33-kDa protein as revealed by 2D electrophoresis of in vitro
      translated in vitro translated proteins using [35S]methionine. The Cd-induced
      synthesis of this transcriptionally regulated protein might be a preindicator for
      a Cd intoxication in enchytraeids.

PMID- 7529170
TI  - Renaturation and activity staining of glycosidases and glycosyltransferases in
      gels after sodium dodecyl sulfate-electrophoresis.
AB  - Glycosidases and glycosyltransferases were electrophoresed in the presence of
      sodium dodecyl sulfate (SDS) in a thin-layer gel supported by a glass plate,
      treated with the nonionic detergent Triton X-100, and specifically stained for
      the sugar-releasing activity of these enzymes. Staining is based on conversion of
      monosugars or a sugar phosphate to glucose-6-phosphate by the appropriate
      intermediary enzymes, reduction of NADP+ to NADPH, and accumulation of reduced
      Nitroblue Tetrazolium in the gel. Among the enzymes tested, alpha-glucosidase,
      beta-glucosidase and beta-mannosidase could not be renatured, whereas beta
      fructofuranosidase and alpha-mannosidase could be renatured unless heated before
      electrophoresis. Sucrose phosphorylase, glucosyltransferase and
      fructosyltransferase, which are single-peptide proteins with no cystine bond,
      could be renatured even after pretreatment with SDS and/or mercaptoethanol at 100
      degrees C for 10 min. However, exclusive heating remarkably decreased the
      activities of these enzymes. Two-dimensional separation of the five renaturable
      enzymes was done in a single thin-layer gel, using SDS-electrophoresis in the
      first dimension and isoelectric focusing in the second dimension.

PMID- 7529171
TI  - Quantitation of electrophoretically separated proteins in the submicrogram range
      by dye elution.
AB  - A new method for the fast, reliable and reproducible submicrogram quantitation of
      proteins separated by different electrophoretic techniques is presented. The
      method is based on a modified sensitive staining technique using Coomassie
      Brilliant Blue G-250 in colloidal solution combined with an optimized elution
      procedure of the bound dye in a 3% w/v solution of sodium dodecyl sulfate
      followed by photometric determination of dye concentration in the eluate. In
      addition a new method is provided for background correction, even suitable for
      gels showing strong background staining. The staining procedure allows the
      detection of 20 ng depending on the nature of the protein and the separation
      technique used. Quantitation is linear at least in the range from 50 ng to 10
      micrograms and highly reproducible even under non-optimized conditions. The
      presented method can be applied to sodium dodecyl sulfate-electrophoresis,
      isoelectric focusing and two-dimensional electrophoresis.

PMID- 7529169
TI  - Detection of exo-beta-1,3-glucanase activity in polyacrylamide gels after
      electrophoresis under denaturing or nondenaturing conditions.
AB  - A method for the visualization of exo-beta-1,3-glucanase activity in
      polyacrylamide gels is presented. The procedure consists of the enzyme reaction
      in the gel with the substrate alpha-naphthylglucopyranoside, and a subsequent
      staining of the obtained alpha-naphthol with dyes Fast Red B, or Fast Blue BB,
      respectively. A mixture of exoglucanases produced by the fungus Polyporus
      squamosus was used for the optimization of the method. The procedure is
      applicable for the standard Laemmli discontinuous electrophoresis system, even in
      the presence of sodium dodecyl sulfate, as well as for electrophoresis in linear
      gradients of the polyacrylamide concentration. The staining method was used for
      the analysis of exoglucanases secreted by several yeast genera. All yeasts tested
      produced two types of exoglucanases, a high molecular mass species heterogeneous
      in size, and one or two smaller homogeneous enzymes.

PMID- 7529172
TI  - Filipin staining of lipoproteins in polyacrylamide gels: sensitivity and
      photobleaching of the fluorophore and its use in a double staining method.
AB  - We have developed a double staining procedure in which polyacrylamide gels are
      first stained with filipin to identify lipoproteins, and then with Coomassie
      Brilliant Blue (CBB) to identify proteins. Filipin staining when performed at 37
      degrees C is both more rapid and more sensitive than previously published
      procedures. After only 5 min, 20 ng of low density lipoprotein (LDL) unesterified
      cholesterol/mm3 of band volume could be detected, and after 12 h, sensitivity
      reached 0.8 ng/mm3. A semilogarithmic relationship was found between the amount
      of LDL unesterified cholesterol applied and filipin fluorescence. Although rapid
      photobleaching of the fluorophore occurred during UV transillumination of these
      gels, such photobleaching actually resulted in maximizing of the signal:noise
      ratio, resulting in better definition of bands. Treatment of gels with filipin
      had no deleterious effects on the subsequent staining with CBB. This dual
      staining procedure should prove useful for studies in which both lipoproteins and
      proteins in plasma need to be documented in the same gel.

PMID- 7529173
TI  - The binding epitopes of neurotrophin-3 to its receptors trkC and gp75 and the
      design of a multifunctional human neurotrophin.
AB  - Survival and maintenance of vertebrate neurons are influenced by neurotrophic
      factors which mediate their signal by binding to specific cell surface receptors.
      We determined the binding sites of human neurotrophin-3 (NT-3) to its receptors
      trkC and gp75 by mutational analysis and compared them to the analogous
      interactions of nerve growth factor (NGF) with trkA and gp75. The trkC binding
      site extends around the central beta-strand bundle and in contrast to NGF does
      not make use of non-conserved loops and the six N-terminal residues. The gp75
      epitope is dominated by loop residues and the C-terminus of NT-3. A novel rapid
      biological screening procedure allowed the identification of NT-3 mutants that
      are able to signal efficiently through the non-preferred receptors trkA and trkB,
      which are specific for NGF and BDNF respectively. Mutation of only seven residues
      in NT-3 resulted in a human neurotrophin variant which bound to all receptors of
      the trk family with high affinity and efficiently supported the survival of NGF-,
      BDNF- and NT-3-dependent neurons. Our results suggest that the specificity among
      neurotrophic factors is not solely encoded in sequence diversity, but rather in
      the way each neurotrophin interacts with its preferred receptor.

PMID- 7529174
TI  - Productive HIV-1 infection of macrophages restricted to the cell fraction with
      proliferative capacity.
AB  - Retroviruses establish productive infection only in proliferating cells.
      Macrophages are often considered to be non-proliferating in vitro yet are
      susceptible to HIV-1 infection. This has led to the conclusion that HIV-1 can
      establish infection independent of host cell proliferation. We here report that a
      small proportion of macrophages does have proliferative capacity. A comparable
      small fraction of monocyte derived macrophages (MDM) supported productive HIV-1
      infection as demonstrated in limiting dilution culture. Fluorescence activated
      cell sorting on the basis of incorporation of BrdUrd, a thymidine analog, and
      subsequent PCR analysis revealed the presence of proviral DNA only in the BrdUrd
      positive cell fraction with DNA synthesizing activity. To identify which phase of
      cell cycle is required for establishment of productive infection, growth arrest
      in G1 or G1/S phase prior to inoculation was performed. gamma-Irradiation, which
      arrests primary cells in G1, prevented both cell proliferation and establishment
      of productive infection in MDM. Treatment of MDM with aphidicolin, a specific
      inhibitor of DNA polymerase alpha and delta which arrests cells in G1/S phase of
      the cell cycle, also inhibited DNA synthesis but did not prevent establishment of
      productive infection which is completely analogous to observations in T cells.
      Our data thus indicate that not cell division itself but cellular conditions that
      coincide with cell proliferation are apparently indispensable for establishment
      of productive infection.

PMID- 7529175
TI  - Immunophilins interact with calcineurin in the absence of exogenous
      immunosuppressive ligands.
AB  - The peptidyl-prolyl isomerases FKBP12 and cyclophilin A (immunophilins) form
      complexes with the immunosuppressants FK506 and cyclosporin A that inhibit the
      phosphatase calcineurin. With the yeast two hybrid system, we detect complexes
      between FKBP12 and the calcineurin A catalytic subunit in both the presence and
      absence of FK506. Mutations in FKBP12 surface residues or the absence of the
      calcineurin B regulatory subunit perturb the FK506-dependent, but not the ligand
      independent, FKBP12-calcineurin complex. By affinity chromatography, both FKBP12
      and cyclophilin A bind calcineurin A in the absence of ligand, and FK506 and
      cyclosporin A respectively potentiate these interactions. Both in vivo and in
      vitro, the peptidyl-prolyl isomerase active sites are dispensable for ligand
      independent immunophilin-calcineurin complexes. Lastly, by genetic analyses we
      demonstrate that FKBP12 modulates calcineurin functions in vivo. These findings
      reveal that immunophilins interact with calcineurin in the absence of exogenous
      ligands and suggest that immunosuppressants may take advantage of the inherent
      ability of immunophilins to interact with calcineurin.

PMID- 7529177
TI  - Molecular cloning and tissue-specific RNA processing of a murine receptor-type
      protein tyrosine phosphatase.
AB  - The molecular cloning of a murine receptor-type protein tyrosine phosphatase,
      termed PTP NU-3, with an extracellular cell-adhesion-molecule-like domain is
      reported. NU-3 was isolated from 11.5-day total mouse embryonic RNA by reverse
      transcriptase PCR using degenerate oligonucleotides flanking the conserved
      protein tyrosine phosphatase catalytic domain. This produced a 280-bp DNA probe
      which was subsequently employed to screen a mouse embryonic kidney library.
      Several overlapping cDNA clones were isolated, collectively forming a cDNA of 6.0
      kb that encodes a putative 211-kDa protein. Northern-blot analysis of total RNA
      from adult and embryonic mouse tissues indicates the existence of two major PTP
      NU-3 transcripts of approximately 6 kb and 7 kb. Both messages are expressed
      predominantly in brain tissues and neuronal-derived cell lines, although
      detectable levels of the 7-kb message were found in other non-neuronal tissues.
      We have identified a unique 132-bp exon segment that is present in the 7-kb
      message but is completely absent in the 6-kb transcript, suggesting tissue
      specific levels of expression and RNA processing. Analysis of the amino acid
      sequence encoded by the 132-bp segment reveals that it completes a partial
      fibronectin type-III element resulting in a protein with a total of nine such
      elements. Bacterial expression of the two catalytic domains demonstrated that
      only the first domain possesses enzymic activity towards a tyrosine
      phosphorylated substrate.

PMID- 7529179
TI  - Presence in frog urinary bladder of proteins immunologically related to the
      aquaporin-CHIP.
AB  - Aquaporin-CHIP, a 28 kDa channel forming protein already referred to as CHIP28,
      has been identified as the water channel in red blood cells as well as in
      mammalian renal tubule cells. Another member of the aquaporin family, WCH-CD, has
      been found in the apical membrane of collecting duct principal cells and may
      represent the ADH-sensitive water channel. The present study investigates the
      possible presence of CHIP28-like proteins in amphibian urinary bladder, where the
      presence of water channels has been postulated. For this purpose, we raised
      polyclonal antibodies against human erythrocyte CHIP28. Immune serum precipitated
      a protein of about 30 kDa from the whole homogenate of urinary epithelial cells.
      By Western blotting, in addition to the reaction with the 30 kDa component, the
      immune serum reacted with higher molecular weight components from the bladder
      homogenate. The 30 kDa band was detected by Western blot only in bladders having
      a high water permeability. Moreover, a 30 kDa protein was also recognized in frog
      red blood cell membranes by the anti-CHIP28 antibodies. In line with the
      immunoblotting studies, in immunohistofluorescence anti-CHIP28 antibodies stained
      frog red blood cells and urinary bladder epithelial cells. However, in whole
      tissue water permeability studies apical treatment with the anti-CHIP28
      antibodies had no effect on either the hydrosmotic response to ADH or on the
      basal net water flow of the bladder. All together, these results indicate the
      presence in the frog red blood cells and urinary epithelium of proteins sharing
      immunological analogies with aquaporin-CHIP.

PMID- 7529178
TI  - Differential regulation of chromogranin B and synapsin I gene promoter activity
      by cAMP and cAMP-dependent protein kinase.
AB  - cAMP has neutrotrophic effects in the nervous system. We have investigated
      whether there is a correlation between cAMP-induced neurite outgrowth and
      induction of chromogranin B and synapsin I gene expression. These genes encode
      marker proteins of distinct populations of vesicles in neurons, neuroendocrine
      and endocrine cells, and in addition, they contain a cAMP response element (CRE)
      in their upstream regions, making it likely that cAMP-induced neuronal
      differentiation might be accompanied by increased transcription of these genes.
      We increased intracellular cAMP levels in neuronal and neuroendocrine cells and
      analyzed the levels of chromogranin B and synapsin I mRNA. Our data revealed
      that, while chromogranin B mRNA was in fact induced following cAMP stimulation,
      synapsin I mRNA was not affected. To analyze the cis-acting sequences, we
      constructed hybrid genes containing the upstream region of the mouse chromogranin
      B gene fused to a reporter gene. Similar plasmids containing the synapsin I or
      the glucagon promoter were constructed. Transfections of neuronal and endocrine
      cells, together with deletion mutagenesis, revealed that the CRE of the
      chromogranin B gene mediated the effect of cAMP upon transcription. This effect
      was mimicked by overexpression of the catalytic subunit of the cAMP-dependent
      protein kinase. In addition, overexpression of the negative-acting CRE-binding
      protein CREB-2 revealed that the chromogranin B CRE functions as a bifunctional
      genetic regulatory element in that it mediates basal as well as cAMP-stimulated
      transcription. Synapsin I gene expression, however, was not induced by either
      elevated intracellular cAMP concentration or by overexpression of protein kinase
      A, although a similar pattern of proteins, including CREB, bound to the synapsin
      I and chromogranin B CRE in vitro. Thus while the CRE element in the chromogranin
      B gene promoter is responsive to cAMP, the same element, when present in the
      synapsin I promoter, does not confer cAMP inducibility.

PMID- 7529180
TI  - An actin infrastructure is associated with eukaryotic chromosomes: structural and
      functional significance.
AB  - The presence of actin in eukaryotic nuclei, and, especially, its functional
      significance has not been well established. We have found that under routine
      immunocytochemical conditions, no actin can be detected in insect follicle cell
      nuclei by means of antibody (both mono- and polyclonal) or phalloidin staining.
      However, a pretreatment of nuclear preparations with two different endonucleases
      (deoxyribonuclease I or micrococcal nuclease) to remove a substantial amount of
      chromosomal DNA uncovers the presence of nuclear actin for both antibody and
      phalloidin detection. Employing the same nuclease digestion followed by antibody
      or phalloidin staining with squash preparations of Drosophila polytene
      chromosomes revealed that the nuclear actin is directly associated with the
      chromosomes. A strong positive signal in the polytene chromosomes obtained with
      phalloidin labeling not only confirmed the presence of actin in the chromosomes,
      but indicates that a considerable amount of nuclear actin is present in
      filamentous form (F-actin) rather than monomeric (G-actin). The detection of
      actin associated with Xenopus embryo chromosomes suggests the significance of
      chromosomal actin for diploid vertebrate cells. Using the specific actin
      disrupting agent cytochalasin D, we have demonstrated the structural significance
      of nuclear actin in maintaining the linear integrity of polytene chromosomes.
      Further, we present evidence that RNA polymerase II closely interacts with the
      chromosomal actin scaffold, and that its association with chromosomes does not
      require the presence of DNA.

PMID- 7529176
TI  - Conformational maturation of CFTR but not its mutant counterpart (delta F508)
      occurs in the endoplasmic reticulum and requires ATP.
AB  - Metabolic labeling experiments followed by immunoprecipitation were performed to
      investigate the kinetics, location and inhibitor sensitivity of degradation of
      both wild-type (wt) and mutant (delta F508) cystic fibrosis conductance
      transmembrane regulator (CFTR). At the earliest stages of the biosynthetic
      process, both wt and delta F508 CFTR were found to be susceptible to degradation
      by endogenous proteases. Virtually all delta F508 CFTR and 45-80% of wt CFTR were
      rapidly degraded with a similar half-life (t1/2 approximately 0.5 h). The
      remaining wt CFTR attained a protease-resistant configuration regardless of
      whether traffic between the endoplasmic reticulum (ER) and Golgi was operational.
      Metabolic energy is required for the conformational transition, but not to
      maintain the stability of the protease-resistant wt CFTR. Intracellular
      degradation of delta F508 CFTR and of incompletely folded wt CFTR occurs in a non
      lysosomal, pre-Golgi compartment, as indicated by the sensitivity of proteolysis
      to different inhibitors and temperature. Accordingly, products of the degradation
      of delta F508 CFTR could be detected by immunoblotting in isolated ER, but not in
      the Golgi. Together, these results suggest a dynamic equilibrium between two
      forms of wt CFTR in the ER: an incompletely folded, protease-sensitive form which
      is partially converted by an ATP-dependent process to a more mature form that is
      protease-resistant and capable of leaving the ER. The inability delta F508 CFTR
      to undergo such a transition renders it susceptible to complete and rapid
      degradation in a pre-Golgi compartment.

PMID- 7529181
TI  - ATP gamma S induces actin and myosin rearrangement during histamine secretion in
      a rat basophilic leukemia cell line (RBL-2H3).
AB  - Rat basophilic leukemia cells (RBL-2H3) undergo morphological and cytoskeletal
      changes during antigen (DNP-BSA) or calcium ionophore-induced secretion of
      allergic mediators from intact or permeabilized cells. We describe the novel
      finding that the phosphatase-resistant ATP analogue, ATP gamma S, mimics antigen
      induced serotonin secretion and cytoskeletal rearrangements in permeabilized
      cells. Confocal microscopy of unstimulated cells shows that myosin and F-actin
      are concentrated at the plasma membrane. Upon addition of ATP gamma S, F-actin
      becomes rearranged into membrane ruffles and also associates with myosin in a
      cytoplasmic meshwork, concentrated perinuclearly. F-actin and myosin ultimately
      become colocalized into parallel microfilament bundles located on the basolateral
      membrane. During this period the cell height decreases whilst the cell area
      increases more than twofold. Gel electrophoresis shows that the cytoskeletal
      proportion of actin remains unchanged, indicating that the rearrangements occur
      within the total F-actin pool. The distribution of microtubules and intermediate
      filaments is unchanged in the presence of ATP gamma S. These results suggest that
      overcoming a phosphatase may be sufficient to induce secretion in RBL-2H3 cells,
      and that this secretion may be regulated by F-actin and myosin rearrangements.

PMID- 7529182
TI  - Excitatory amino acid neurotransmission through both NMDA and non-NMDA receptors
      is involved in the anticonvulsant activity of felbamate in DBA/2 mice.
AB  - The anticonvulsant activity of felbamate against sound-induced seizures was
      studied in the DBA/2 mouse model. Felbamate (10-300 mg/kg, i.p.) produced dose
      dependent effects with ED50 values for the suppression of tonic, clonic and wild
      running phases of 23.1, 48.8 and 114.6 mg/kg, respectively. Felbamate also
      protected DBA/2 mice from N-methyl-D-aspartate (NMDA)-induced seizures with ED50
      values of 12.1 and 29 mg/kg for tonus and clonus, respectively. Pretreatment with
      glycine, an agonist to the glycine/NMDA receptors, shifted the dose-response
      effect of felbamate to the right (ED50 = 56.8 against tonus and 94.8 mg/kg versus
      clonus). Similarly, D-serine, an agonist at the glycine site, shifted the ED50 of
      felbamate against the tonic component of audiogenic seizures from 23.1 to 78.1,
      and that against clonus from 48.8 to 90.3 mg/kg. Felbamate was also potent to
      prevent seizures induced by administration of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA), an AMPA/kainate receptor agonist (ED50 = 11.8 and
      20.9 mg/kg, against tonus and clonus, respectively). The data indicate that
      felbamate is an effective anticonvulsant drug in the genetic model of seizure
      prone DBA/2 mice. Our findings suggest that the anticonvulsant properties of
      felbamate depend upon its interaction with neurotransmission mediated by both the
      glycine/NMDA and the AMPA/kainate receptor complex.

PMID- 7529183
TI  - Non-specific inhibition of dopamine receptor agonist-induced behaviour by the
      tachykinin NK1 receptor antagonist CP-99,994 in guinea-pigs.
AB  - Evidence that tachykinin NK1 receptors selectively modulate activity in the
      mesolimbic dopamine pathway suggests an antipsychotic potential for tachykinin
      NK1 receptor antagonists. We investigated the ability of the antagonist CP-99,994
      (and the less active enantiomer CP-100,263) to block dopamine receptor agonist
      induced behaviour in guinea-pigs. The active dose range for inhibition of
      [Sar9,Met(O2)11]substance P-induced behaviour by CP-99,994 was 1-3 mg/kg s.c. The
      same doses of CP-100,263 were without effect. In contrast, both CP-99,994 (20 or
      30 mg/kg) and CP-100,263 (10-30 mg/kg) antagonised behavioural stimulation
      induced by the dopamine receptor agonists amphetamine (1 mg/kg i.p.) or (+)-PHNO
      ((+)-4-propyl-9-hydroxy-naphthoxazine hydrochloride; 0.1 mg/kg s.c.). Lower doses
      of CP-99,994 or CP-100,263 were not active. These findings do not support the
      proposal that tachykinin NK1 receptors in the terminal projection area of the
      mesolimbic system can modify dopamine-mediated behaviour.

PMID- 7529185
TI  - Intracellular sex hormone-binding globulin (SHBG) in normal and neoplastic breast
      tissue--an additional marker for hormone dependency?
AB  - Recent studies indicate that in addition to free diffusion, uptake of sex
      hormones into target cells is mediated by sex hormone-binding globulin (SHBG).
      The purpose of this study was to investigate localization and distribution of
      SHBG in normal and neoplastic breast tissue. We examined 31 normal, 21 non
      invasive, 52 invasive breast cancer tissues and 33 cases of recurrences and
      metastases of breast cancer immunohistochemically for SHBG by the ABC-peroxidase
      method, using a polyclonal, monospecific antiserum derived from rabbit. The
      proportion of stained cells was evaluated semiquantitatively. In 81 malignant
      cases the oestrogen receptor (ER) content was evaluated by the ER-ICA method.
      Positive staining for SHBG was found exclusively in epithelial cell cytoplasm.
      Benign tissue was focally SHBG-positive and showed more stained cells in
      proliferating epithelium. Staining of neoplastic tissue was more heterogeneous.
      Half of the non-invasive carcinomas were SHBG-positive; particularly the highly
      differentiated. Independent of subtype and differentiation, invasive tumours were
      SHBG-negative in 32.5% of cases, while 19.3% were SHBG-positive in most cells. In
      13 cases of invasive carcinomas, associated intraductal parts showed more
      staining for SHBG than the invasive tissue. Recurrences and metastases of breast
      cancer were SHBG-negative in 45.5% of cases, while only 3% were positive in most
      cells. SHBG-staining was unrelated to ER content. These results suggest that the
      demonstration of cytoplasmic SHBG represents a physiological feature of breast
      epithelium and its presence is compatible with a mechanism for cellular uptake of
      SHBG-bound sex hormones preceding their interaction with nuclear
      receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529184
TI  - Nitric oxide modulates prostacyclin biosynthesis in the lung of endotoxin-treated
      rats.
AB  - In this study we have investigated the correlation between prostaglandin
      generation and the L-arginine:nitric oxide (NO) pathway in the lung of rats
      challenged with lipopolysaccharide. We found that in rats treated with L
      arginine, the amount of prostacyclin, measured as 6-keto-PGF1 alpha, was
      significantly increased. Conversely in rats treated with NG-nitro-L-arginine
      methyl ester the production of 6-keto-PGF1 alpha by lung was significantly
      decreased. Chopped lungs that had been removed from rats challenged with
      lipopolysaccharide and were incubated overnight with L-arginine or nitric oxide
      inhibitors, NG-nitro-L-arginine methyl ester or NG-monomethyl-L-arginine,
      released respectively increased or decreased amount of 6-keto-PGF1 alpha. These
      results suggest that, in the rat, lung endogenous nitric oxide may modulate
      prostanoid production.

PMID- 7529186
TI  - Two hnRNP-associated proteins share common structural features with the
      adenoviral 72-kDa protein.
AB  - Using our anti-hnRNP monoclonal antibody library Y. Lutz, M. Jacob, and J.-P.
      Fuchs (1988) Exp. Cell Res., 175, 108-124; P. Mahl, Y. Lutz, E. Puvion, and J.-P.
      Fuchs, (1989) J. Cell Biol. 109, 1921-1935, we investigated by
      immunocytofluorescence the fate of a series of speckled-distributed nuclear
      antigens, after HeLa cells were infected with adenovirus type 2. Although the
      speckled pattern, which corresponds to the nucleoplasmic fibrillogranular
      network, including the interchromatin-granule clusters, was still observed during
      most of the infectious cycle, several antibodies also revealed additional,
      increasingly fluorescent virus-induced structures. In noninfected cells, two of
      these antibodies, termed 3F2 and 2A5, recognize two antigens of 33 and 31 kDa,
      respectively. Western blot analysis showed that this increasing amount of
      fluorescence observed in infected cells did not reflect an accumulation of the 33
      and 31-kDa antigens, but is actually due to the fact that both antibodies also
      recognize the multifunctional adenovirus 72-kDa single-stranded DNA-binding
      protein (DBP). Immunoelectron microscopy analyses, including sequential double
      labeling, indeed showed that this additional signal precisely colocalizes with
      the viral 72-kDa DBP, which essentially accumulates over the entire surface of
      the virus-induced single-stranded DNA accumulation sites. Taken together, our
      data show that two host-specific hnRNP-associated antigens share common epitopes
      with the viral 72-kDa DBP.

PMID- 7529187
TI  - Induction of expression of interferon-stimulated gene factor-3 (ISGF-3) proteins
      by interferons.
AB  - Interferon-stimulated gene factor-3 (ISGF-3) is a multiprotein (113, 91, 84, and
      48 kDa) transcriptional factor which regulates the expression of a specific set
      of genes, the interferon (IFN)-stimulated genes. In the studies presented here,
      we investigated the induction of synthesis of proteins of the ISGF-3 complex by
      IFNs. We report that both IFN-alpha and IFN-gamma induce a 3- to 5-fold increased
      expression of p91, p84, and p113 and their phosphotyrosine contents in a dose-
      and time-dependent manner. The IFN-mediated induction in the levels of p91
      correlated well with the increased expression of steady-state levels of p91 mRNA
      by IFNs. Increased levels of p91 and p84 became detectable after 6 and 4 h
      treatment with IFN-alpha and IFN-gamma, respectively, and reached a maximum 5.2
      fold at 18 h by IFN-alpha and 4-fold at 15 h by IFN-gamma. The levels of p113
      were induced up to 3-fold at 15 h by IFN-alpha or IFN-gamma. The induction of
      ISGF-3 proteins by IFNs was accompanied by an increase in the accumulation of
      p91, p84, and p113 in the nucleus. The observed induction of increased expression
      of ISGF-3 proteins does not require continuous presence of IFNs, as removal of
      IFNs after 6 h of minimal treatment still resulted in a significant increase (2-
      to 4-fold) in the levels of expression of p91, p84, and p113 over an additional
      period of 12 h in culture, and induced proteins remained phosphorylated on
      tyrosine. The IFN-mediated increase in the synthesis of ISGF-3 proteins was
      blocked by Actinomycin D. Extension of these investigations to other human and
      mouse responsive cells, Daudi, Hela, and NIH3T3, also demonstrated significant
      increase in the levels of p91, p84, and p113 by interferons.

PMID- 7529188
TI  - Characterization of human colon carcinoma variant cells selected for sialyl Lex
      carbohydrate antigen: liver colonization and adhesion to vascular endothelial
      cells.
AB  - The content of sialyl Lewis-X antigen (Neu5Ac alpha 2-3Gal beta 1-4(fuc alpha 1
      3)GlcNAc-R: sialyl Le(x)) was previously shown to correlate with the progression
      of human colon carcinomas to the advanced stages. Variant cell lines with high
      (KM12-HX) or low (KM12-LX) levels of cell surface sialyl Le(x) were isolated from
      the heterogeneous KM12C cells to characterize the biological behavior of colon
      carcinoma cells with elevated cell surface contents of sialyl Le(x). When these
      cells were injected intrasplenically into nude mice, KM12-HX cells colonized to
      the liver more efficiently than KM12-LX cells. Under in vitro conditions, KM12-HX
      cells demonstrated greater degree of adhesion to cytokine-activated human
      umbilical vein endothelial cells than KM12-LX cells. The adhesion of KM12-HX
      cells was partially inhibited by antibodies specific for E-selectin, which was
      known to serve as a ligand for the sialyl Le(x) carbohydrate antigen. The
      treatment of KM12-HX cells with benzyl N-acetyl-alpha-D-galactosaminide, a
      putative inhibitor of the extension of O-linked carbohydrate chains, reduced the
      rate of adhesion. These results suggested that the interaction of endothelial
      cell surface E-selectin with O-linked carbohydrate chains on colon carcinoma cell
      surface glycoproteins played an important role in the adhesion.

PMID- 7529189
TI  - Epidermal growth factor enhancement of HSC-1 human cutaneous squamous carcinoma
      cell adhesion and migration on type I collagen involves selective up-regulation
      of alpha 2 beta 1 integrin expression.
AB  - Some human neoplasms show aberrant expression or overexpression of epidermal
      growth factor (EGF) receptor, and the degree of the receptor expression is
      correlated with the malignant phenotype in certain epithelial tumors including
      squamous carcinoma cells. Since phenotypic transformation of cells could involve
      quantitative and qualitative alteration of integrin function, the effects of EGF
      on cell-matrix interactions were studied using HSC-1 cells, a human squamous
      carcinoma cell line showing EGF receptor overexpression. The EGF-treated HSC-1
      cells interacted with matrix proteins differently from the untreated cells, as
      shown by cell adhesion and phagokinetic track assays. Among fibronectin, laminin,
      fibrinogen, and type I collagen, fibronectin was the most efficient substratum to
      promote untreated HSC-1 cell adhesion and migration. Pretreatment of the cells
      with 50 ng/ml EGF for 18 h selectively increased the number of spread cells and
      the size of the individual cell migration area on type I collagen by 250 and
      400%, respectively. The same pretreatment diminished cell adhesion and migration
      on other substrata so that the EGF treatment converted type I collagen as the
      most efficient substratum for cell adhesion and migration of the HSC-1 cells.
      ELISA and immunoprecipitation studies showed that EGF up-regulated the expression
      of alpha 2 beta 1 integrin collagen receptor in a time- and dose-dependent manner
      by stimulating biosynthesis of alpha 2 subunit, but did not up-regulate those of
      the alpha 3 beta 1, alpha 5 beta 1, or alpha v beta 3 integrins. These results
      suggest that EGF preferentially enhances HSC-1 cell interaction with type I
      collagen, leading to the enhanced cellular migratory activity on the substratum,
      as a result of selective up-regulation of alpha 2 beta 1 integrin expression.

PMID- 7529190
TI  - Possible involvement of the interaction of the alpha 5 subunit of alpha 5 beta 1
      integrin with the synergistic region of the central cell-binding domain of
      fibronectin in cells to fibronectin binding.
AB  - The interaction between the central cell-binding domain (CBD) of fibronectin (FN)
      and its receptor integrin alpha 5 beta 1 was analyzed by both ligand-binding and
      cell adhesion assays. The ligands used were a CBD fragment (pCBD) of human plasma
      fibronectin and its recombinant versions including wild type CBD (wtCBD) and its
      two mutants (CBD-I, lacking the integrin recognition sequence Arg-Gly-Asp from
      wtCBD and CBD-II, missing the synergistic regions). The ligand-binding assay
      showed that CBD-I and CBD-II bind to the receptor, although the binding ability
      of the former was weaker than that of the latter. The affinity of pCBD to the
      receptor was much higher than the two mutants. The cell adhesion assay also
      revealed that cells were able to attach and spread on CBD-I to the same extent as
      on CBD-II, although the extent of spreading on the two mutant polypeptides was
      less than 4.1% of pCBD or wtCBD. On the other hand, beta 1-dependent cell
      spreading on CBD-II was not inhibited by the monoclonal antibody specific for the
      alpha 5 subunit, while that on CBD-I, wtCBD, or pCBD was inhibited by the same
      antibody. The present study suggests that the alpha 5 subunit does not
      participate in direct binding to the Arg-Gly-Asp site in CBD when cells adhere to
      FN through the integrin alpha 5 beta 1, but that it is involved in the
      interaction with the synergistic regions of CBD, which then enhances the binding
      of the beta 1 subunit to the Arg-Gly-Asp sequence containing CBD.

PMID- 7529191
TI  - Transforming growth factor-beta 1 (TGF beta 1) enhances apoptosis in human
      papillomavirus type 16-immortalized human ectocervical epithelial cells.
AB  - Transforming growth factor beta (TGF beta) is a potent inhibitor of epithelial
      cell growth. In the present study TGF beta 1 modulation of human ectocervical
      epithelial cell growth and differentiation is evaluated using an HPV16
      immortalized human ectocervical cell line, ECE16-1. These cells were found to
      contain a high-affinity receptor for TGF beta 1 (Kd = 75 pM). TGF beta (10-500
      pg/ml) suppressed ECE16-1 growth and [3H]thymidine incorporation in a dose
      dependent manner. Growth inhibition was reversible at TGF beta 1 concentrations
      of 100 pg/ml or less. At higher concentrations of TGF beta 1, treatment for
      longer than 2 days induced irreversible growth inhibition. In addition to its
      effects on cell growth, TGF beta 1 treatment increased apoptosis in ECE16-1 cells
      as measured by an increase in cornified envelope formation, flow cytometry, and
      DNA fragmentation. Apoptosis was enhanced at doses > or = 100 pg/ml. There was a
      highly significant increase in the activity of tissue transglutaminase, an enzyme
      believed to play an important role in apoptosis. This increase in
      transglutaminase activity was paralleled by a TGF beta 1-stimulated increase in
      fibronectin levels. Transglutaminase and fibronectin have been shown to associate
      during tissue remodeling. These data suggest that TGF beta 1 may act as an
      important paracrine/autocrine factor to stimulate normal cervical remodeling and
      to limit HPV16-immortalized cervical cell progression by stimulating apoptosis.
      The induction of fibronectin and tissue transglutaminase suggests that the TGF
      beta 1 pathway of cell death differs from that of normal ectocervical epithelial
      cell differentiation, which is mediated by epidermal transglutaminase.

PMID- 7529192
TI  - Anatomical evidence for ipsilateral collicular projections to the spinal cord in
      the cat.
AB  - Injections of WGA-HRP were made within the C1 segment of spinal cord in cats with
      a midsagittal section of the midbrain. A small number of labelled cells were
      found in the latero-caudal part of the deeper layers of the superior colliclus
      (SC) ipsilateral to the injection sites. Because of the complete section of the
      dorsal tegmental decussation, these results definitively demonstrate the
      existence of an ipsilateral tecto-spinal pathway projecting to upper cervical
      segments in the cat. Ipsilaterally projecting tecto-reticulo-spinal neurons
      represent about 5% of the total population of tecto-spinal neurons. They were
      exclusively located in the deeper collicular layers and most of them were found
      in the latero-caudal part of the SC. Comparison with our previous studies
      suggests that more ipsilateral tecto-spinal projections that found after the
      section of the dorsal tegmental decussation probably exist. They may arise from
      tecto-reticulo-spinal neurons recrossing the midline in the brainstem or in the
      rostral part of C1. By analogy with the cortico-spinal tract, we suggest that the
      existence of an ipsilateral tecto-spinal pathway can be regarded as evidence for
      a substantial development of the cat tecto-spinal system as compared with other
      mammals.

PMID- 7529193
TI  - Subthreshold rectification in neostriatal spiny projection neurons.
AB  - Intracellular recordings from slice preparations were used to assess the
      subthreshold electrophysiological behavior of rat neostriatal projection neurons.
      Both current steps and ramp currents were used to estimate the current-voltage
      relationship (I-V plot). Inward rectification in the subthreshold range was a
      characteristic of most neurons. The amount of rectification varied greatly, and
      it was complex: membrane voltage trajectories in response to ramps were made up
      by almost piece-wise changes in the rate of voltage rise, suggesting that
      multiple conductances contribute to the subthreshold range. Inward current
      blockers such as tetrodotoxin (TTX) or Cd2+ decreased inward rectification,
      whereas outward current blockers such as tetraethylammonium (TEA) or 4
      aminopyridine (4-AP) increased inward rectification. However, most inward
      rectification was due to TEA- and Cs(+)-sensitive conductances and not to TTX- or
      Cd(2+)-sensitive conductances. Cs(+)-sensitive conductances predominated at more
      negative membrane potentials, whereas 4-AP-sensitive conductances predominated at
      just +/- 10 mV below the firing threshold. In spite of a very slow activation,
      there was evidence for transient outward currents modulating the response, i.e.,
      4-AP-sensitivity, and voltage-sensitivity for firing frequency and threshold. TEA
      sensitive conductances also contributed toward fixing the firing threshold. These
      results imply the contribution of various ion conductances on the shaping of the
      characteristic physiological firing recorded in vivo. Modulation of these
      responses by transmitters or peptides may help to understand neural processing in
      the neostriatum.

PMID- 7529195
TI  - Sprouting of remaining substance P-immunoreactive fibers in the monkey dentate
      gyrus following denervation from its substance P-containing hypothalamic
      afferents.
AB  - This study analyzed the response of intrinsic substance P-immunoreactive fibers
      in the monkey dentate gyrus to disruption of the supramammillo-hippocampal
      projection. This projection normally forms a thin plexus of large, substance P
      immunoreactive terminals in the innermost portion of the dentate molecular layer
      and establishes exclusively asymmetric synapses with dendritic shafts and spines
      of dentate neurons. Conversely, substance P-containing terminals have never been
      observed in synaptic contact with granule cell bodies. Ten days after ipsilateral
      fimbria-fornix transection, the prominent band of large immunostained axons in
      the inner molecular layer of the ipsilateral fascia dentata disappeared. Four and
      five weeks following transection, however, some small, substance P-containing
      terminals were observed in the innermost portion of the dentate molecular layer
      and the granule cell layer. These terminals established exclusively symmetric
      synapses with the somata and proximal dendritic shafts of granule cells. These
      results suggest that, following transection of the hypothalamo-hippocampal fiber
      tract, presumptive intrinsic substance P-containing axons are capable of
      sprouting into the granule cell layer and the former termination field of the
      hypothalamic fibers. The symmetric synapses established with granule cell bodies
      and their proximal dendrites might indicate a shift from an extrinsic excitation
      to an intrinsic inhibition of granule cells following disruption of substance P
      containing hypothalamic afferents.

PMID- 7529194
TI  - Efferent connections of the medial prefrontal cortex in the rabbit.
AB  - The different cytoarchitectonic regions of the medial prefrontal cortex (mPFC)
      have recently been shown to play divergent roles in associative learning in
      rabbits. To determine if these subareas of the mPFC, including areas 24 (anterior
      cingulate cortex), 25 (infralimbic cortex), and 32 (prelimbic cortex) have
      differential efferent connections with other cortical and subcortical areas in
      the rabbit, anterograde and retrograde tracing experiments were performed using
      the Phaseolus vulgaris leukoagglutinin (PHA-L), and horseradish peroxidase (HRP)
      techniques. All three areas showed local dorsal-ventral projections into each of
      the other areas, and a contralateral projection to the homologous area on the
      other side of the brain. All three also revealed a trajectory through the
      striatum, resulting in heavy innervation of the caudate nucleus, the claustrum,
      and a lighter projection to the agranular insular cortex. The thalamic
      projections of areas 24 and 32 were similar, but not identical, with projections
      to the mediodorsal nucleus (MD) and all of the midline nuclei. However, the
      primary thalamic projections from area 25 were to the intralaminar and midline
      nuclei. All three areas also projected to the ventromedial and to a lesser extent
      to the ventral posterior thalamic nuclei. Projections were also observed in the
      lateral hypothalamus, in an area just lateral to the descending limb of the
      fornix. Amygdala projections from areas 32 and 24 were primarily to the lateral,
      basolateral and basomedial nuclei, but area 25 also projected to the central
      nucleus. All three areas also showed projections to the midbrain periaqueductal
      central gray, median raphe nucleus, ventral tegmental area, substantia nigra,
      locus coeruleus and pontine nuclei. However, only areas 24 and the more dorsal
      portions of area 32 projected to the superior colliculus. Area 25 and the ventral
      portions of area 32 also showed a bilateral projection to the parabrachial nuclei
      and dorsal and ventral medulla. The dorsal portions of area 32, and all of area
      24 were, however, devoid of these projections. It is suggested that these
      differential projections are responsible for the diverse roles that the
      cytoarchitectonic subfields of the mPFC have been demonstrated to play in
      associative learning.

PMID- 7529197
TI  - Towards therapy of Gaucher's disease by gene transfer into hematopoietic cells.

PMID- 7529196
TI  - Evaluation of indeterminate sera for hepatitis C virus by assays using synthetic
      peptides.
AB  - The development of new immunodiagnostic systems to study antibodies anti-HCV
      based on the use of synthetic peptides are potentially very important in the
      evaluation of indeterminate samples. We have compared two immunodiagnostic tests,
      the 3-RIBA and LIA-HCV test system, to examine the samples rated as indeterminate
      by the 2-RIBA test. The results showed that the specificity of the new tests has
      improved, in fact 29/40 of the indeterminate samples studied became positive with
      both tests. However, the 3-RIBA test showed higher sensitivity, since two samples
      negative by LIA-HCV, were positive with this system.

PMID- 7529198
TI  - Flow cytometric reticulocyte quantification in the evaluation of hematologic
      recovery. Spanish Multicentric Study Group for Hematopoietic Recovery.
AB  - The role of flow cytometric reticulocyte (RET) counting and the immature RET
      fractions (IRF) in the evaluation of hematopoietic recovery following
      chemoradiotherapy-induced aplasia was studied. RET counts and IRF were studied
      using an automated flow cytometric reticulocyte counter (Sysmex R-2000) in three
      groups of patients: 58 patients undergoing an autologous bone marrow
      transplantation (ABMT group), 28 of whom received granulocyte colony-stimulating
      factor (G-CSF); 28 patients undergoing an allogeneic bone marrow transplantation
      (BMT group); and 28 patients receiving remission-induction chemotherapy for acute
      leukemia (CHEMO group). To evaluate the IRF the percentages of RET fractions with
      middle and high fluorescence reticulocyte (MFR and HFR, respectively) were used.
      A rising IRF (expressed as the percentage of MFR + HFR) was the first sign of
      hematopoietic recovery (ABMT group, IRF 9 days versus 18 days for the absolute
      neutrophil count (ANC); BMT group, 15 versus 18 days; CHEMO group, 9 versus 11
      days). When recovery of the ANC (> 0.5 x 10(9)/l) was compared with that of the
      iRF (MFR + HFR > 5%), statistically significant differences were found in all
      three groups. Additionally, 93.1% of the ABMT, 92% of the BMT and 91.2% of the
      CHEMO recovered the IRF before the ANC. In conclusion, an elevation in the
      percentage of IRF is the first sign of hematologic recovery in the majority of
      patients receiving remission-induction chemotherapy and the first sign of
      engraftment in those submitted to ABMT or BMT. Serial automated flow cytometric
      quantitative reticulocyte counting provides a useful and early measure of
      erythropoiesis indicative of hematopoietic reconstitution or successful bone
      marrow engraftment following marrow transplantation.

PMID- 7529199
TI  - Management of patients with persistent beta-hCG values following laparoscopic
      surgical and local drug treatment for ectopic pregnancy.
AB  - OBJECTIVES: To show that the beta-human chorionic gonadotropin (hCG) decline
      following tubal-preserving techniques for ectopic pregnancy (EP) can take a
      longer course than currently believed, indicating expectant management; and to
      define the indications for a second-look laparoscopy if beta-hCG persists.
      METHODS: Three hundred thirty-seven patients treated for EP were retrospectively
      reviewed. In order to define the 'normal' beta-hCG decline following tubal
      preserving techniques we acquired a Kaplan-Meier curve for 98 patients treated by
      laparoscopic linear salpingotomy, the main method performed for EP (253
      patients). The Mann-Whitney U-test served as a statistical test. The patient
      population requiring a second-look laparoscopy for proliferating trophoblastic
      remnants is described. RESULTS: Twenty-eight patients (8.3%) required a second
      look laparoscopy (acute abdominal pain and sonographically suspect findings
      combined with increasing beta-hCG values). The majority (15 patients) underwent a
      preceding laparoscopic linear salpingotomy (6.5% unresolved cases). The relative
      beta-hCG values differed significantly from the unresolved group compared to the
      group with resolved EP starting at postoperative day 2 (P < 0.01). A maximal beta
      hCG decline period of 77 days postoperatively was observed. CONCLUSIONS: Patients
      with slowly declining beta-hCG levels following tubal-preserving techniques for
      EP can be managed expectantly. Increasing beta-hCG values combined with abdominal
      pain and sonographically suspect observations indicate a second-look laparoscopy.

PMID- 7529200
TI  - Spontaneous reseal of high-leak PROM following genetic amniocentesis.

PMID- 7529202
TI  - Insulin secretagogues, but not glucose, stimulate an increase in [Ca2+]i in the
      fetal rat beta-cell.
AB  - Fetal pancreatic islets release insulin poorly in response to glucose; however,
      the cellular mechanism for this is controversial. By using fura 2 to measure
      changes in the cytoplasmic free Ca2+ concentration ([Ca2+]i) in beta-cells, we
      have examined islets from fetal, neonatal, and adult rats to determine the
      ability of glucose and other secretagogues to cause an increase in [Ca2+]i. The
      effects of glucose (20 mmol/l), glyceraldehyde (20 mmol/l), leucine (20 mmol/l),
      arginine (20 mmol/l), and the channel effectors glipizide (50 mumol/l), BAY K8644
      (2 mumol/l), diazoxide (300 mumol/l), and verapamil (20 mumol/l) on changes in
      [Ca2+]i were studied. In both the fetal and the mature islet, glyceraldehyde,
      leucine, arginine, glipizide, and BAY K8644 caused an increase in [Ca2+]i. In
      mature islets, glucose also increased [Ca2+]i; however, in the fetal islet,
      glucose had no effect on [Ca2+]i. The stimulus-induced increases in [Ca2+]i in
      fetal and adult islets were both significantly inhibited by the addition of
      either diazoxide or verapamil. Similar results were obtained when insulin
      secretion was measured. Our data show that various secretagogues are able to
      stimulate fetal islets and cause an increase in [Ca2+]i. Glucose, however, fails
      to cause an increase in [Ca2+]i in the fetal islet. Hence, the immature insulin
      secretory response to glucose by the fetal islet is due to the inability of the
      fetal beta-cell to translate glucose stimulation into the increase in [Ca2+]i
      required for exocytosis of the insulin granule.

PMID- 7529201
TI  - Phosphorylation of the Drosophila adherens junction protein Armadillo: roles for
      wingless signal and zeste-white 3 kinase.
AB  - The Drosophila segment polarity gene product Armadillo provides a link between
      two seemingly separate processes, regulation of segmental pattern by the Wingless
      intercellular signal and the function of cell-cell adherens junctions. armadillo
      was originally identified because of its segment polarity phenotype but
      subsequently was found to be the homolog of the vertebrate adherens junction
      protein beta-catenin. We examined the nature of the post-translational
      modification of Armadillo and its possible role in regulating Armadillo function.
      Armadillo is a phosphoprotein. Its level of phosphorylation varies both during
      embryonic development and from tissue to tissue. Phosphorylation occurs on both
      serine or threonine and tyrosine residues. Finally, Wingless signal negatively
      regulates Armadillo phosphorylation, while the segment polarity gene product
      Zeste-white 3, a serine/threonine protein kinase, promotes Armadillo
      phosphorylation. We discuss the implications of these results for regulation of
      Wingless/Wnt-1 signaling and adherens junction function.

PMID- 7529203
TI  - Comparative analysis of vascular endothelial growth factor receptors on retinal
      and aortic vascular endothelial cells.
AB  - Ischemic eye disease often results in ocular neovascularization, presumably due
      to the elaboration of growth factors. Diabetic retinopathy is a classic example
      in which dramatic retinal neovascularization arises after ischemic retinal
      damage. The characterization of vascular endothelial growth factor (VEGF) as an
      angiogenic molecule whose expression is markedly induced by hypoxia makes it a
      promising candidate for mediating ischemic retinal neovascularization. Thus, we
      have characterized the structure, binding, and regulation of VEGF receptors in
      bovine retinal (BREC) and aortic endothelial cells (BAEC). VEGF stimulated a 2.1
      fold increase in BREC number and DNA content at 0.6 nmol/l VEGF (P < 1 x 10(-7)).
      Scatchard binding analysis demonstrated specific high-affinity VEGF receptors on
      BREC with a Kd of 4.9 +/- 0.6 x 10(-11) mmol/l, similar to that observed for BAEC
      at 5.1 +/- 0.4 x 10(-11) mmol/l. BREC, however, possess 1.5 x 10(5) high-affinity
      receptors/cell, threefold more than BAEC (P < 0.003) and more than any cell type
      reported previously. 125I-VEGF affinity cross-linking revealed complexes at 220
      and 170 kDa in BREC, but only a 220-kDa band of lesser intensity in BAEC. Cross
      linking was displaceable in a dose-dependent manner by VEGF (P < 0.01) but not by
      other hormones. Hypoxia increased VEGF receptor number 50% in BREC without
      altering affinity. Antiphosphotyrosine immunoblotting showed VEGF-stimulated
      tyrosine autophosphorylation of VEGF receptor bands at 225 and 220 kDa and
      another band at 80 kDa within 1 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529204
TI  - Protein tyrosine phosphorylation in Mycobacterium tuberculosis.
AB  - Crude cell extracts from three strains of Mycobacterium tuberculosis were
      analyzed for the presence of proteins possessing phosphorylated tyrosine
      residues. A protein migrating at approximately 55 kDa was detected using an
      antiphosphotyrosine monoclonal antibody. In addition, less predominant bands were
      observed between 50 kDa and 60 kDa. That M. tuberculosis contains specific
      tyrosine phosphorylated proteins implies that M. tuberculosis has tyrosine kinase
      activity. Examination of other, non-pathogenic mycobacterium species yielded no
      major antiphosphotyrosine reactive proteins. This suggests that the
      antiphosphotyrosine reactive protein is specific to M. tuberculosis strains.
      These results provide evidence that M. tuberculosis contains an
      antiphosphotyrosine reactive protein.

PMID- 7529205
TI  - The use of PCR to monitor the population abundance of six human intestinal
      bacterial species in an in vitro semicontinuous culture system.
AB  - Six PCR primer sets complementary to the 16S rDNAs (rRNA genes) were developed
      and shown to be specific for the following anaerobic bacteria: Clostridium
      clostridiiforme, C. perfringens, C. leptum, Bacteroides vulgatus, B. distasonis,
      and B. thetaiotaomicron, respectively. These primers were used for PCR to detect
      and monitor the bacteria in a semicontinuous culture system designed to mimic
      intestinal microflora in the human gastrointestinal tract. Except for C.
      perfringens, the five species of Bacteroides and Clostridia present in the in
      vitro culture system were detected by the PCR, and the titers varied from 10(-2)
      to 10(-6) dilutions. The role of azo dye reduction by these bacterial species in
      the system was examined and discussed.

PMID- 7529206
TI  - The mammalian genome shaping activity of reverse transcriptase.
AB  - Reverse transcriptase catalyses the conversion of RNA into DNA. This operation
      seems to have largely contributed to the evolution of complex genomes. More than
      10% of a mammalian genome is composed of sequences with reverse transcribed
      origin, most of which consists of repeated sequences (SINEs, LINEs). In spite of
      their simplicity, these sequences can play a key role in evolution by favoring
      illegitimate recombination. In addition to this abundant material,
      retrotransposed sequences include retrotransposons, retroviruses and genes
      depleted from intervening sequences, known as pseudogenes. Some of these
      sequences can be functional or involved in the regulation of neighbouring genes.
      These hallmarks of reverse transcription activity indicate that it has largely
      contributed to the fluidity of modern genomes.

PMID- 7529208
TI  - Mobile group II introns, DNA circles, reverse transcriptase and senescence (group
      II introns, transposition, aging, mitochondria, fungi).

PMID- 7529207
TI  - Emergence of master sequences in families of retroposons derived from 7sl RNA.
AB  - The past few years have brought new insight into the evolution of families of
      retroposons. These are composed of a very small number of master sequences able
      to duplicate, and a large majority of copies that are inactive for retroposition.
      During the course of time, successive replacements of master sequences have
      produced waves of amplification that are recognizable as subfamilies. In the Alu
      and the B1 families, one can distinguish two evolutionary periods. The first
      involves only monomeric elements that are now extinguished (fossil elements) and
      is characterized by deep remodeling of the sequences. This period ends, in
      primates, with the fusion of a free left and a free right Alu monomer, producing
      the first modern Alu dimeric element; in rodents it ends with a tandem
      duplication of 29 bp to create the first modern B1 element. The second period is
      characterized by a great stability of the master sequences. The observed turn
      over of master sequences is still an enigma. However, analysis of the
      contemporary master sequences and of the oldest master sequences provide some
      clues. Here, we review the very first stages of the appearance of the Alu and the
      B1 families in mammalian genomes.

PMID- 7529209
TI  - Media aids in dental distance learning.
AB  - The need for continuing education on a wide scale necessitates the use of
      techniques that are effective irrespective of the geographical spread or isolated
      locations of potential participants. This paper reviews the many possibilities
      for distance learning in dentistry made feasible by use of these different
      techniques and media.

PMID- 7529210
TI  - Tenascin-C in serum: an acute-phase protein or a carcinoma marker?

PMID- 7529211
TI  - The expression profile of alternatively spliced neuronal c-src RNA distinguishes
      between human tumours of the sympatho-adrenal lineage.
AB  - Human neuronal and neuroendocrine tumour specimens and cell lines were analysed
      regarding proteins and transcripts coded by the proto-oncogene c-src. At the
      protein level, most of the neuroblastomas and phaeochromocytomas expressed the
      neuronal c-src form, pp60c-srcN. None of the other neuroendocrine tumours, i.e.
      paragangliomas, neuroendocrine pancreatic tumours, or carcinoid tumours and small
      cell lung carcinomas of different types, appeared to express the neuronal form.
      In the brain, c-src is transcribed into 3 differently spliced mRNA variants, c
      src, c-srcNI, and c-srcNI+NII. The expression of these transcripts was analysed
      by PCR amplification of fragments covering the mini-exons I and NII of the
      corresponding cDNAs. The PCR products were analysed by Southern hybridization and
      characterized by determination of their sequences. Neuroblastomas,
      paragangliomas, retinoblastomas and the phaeochromocytomas expressed neuronal c
      src splice variants. However, whereas neuroblastomas and retinoblastomas
      contained all 3 transcripts, the phaeochromocytomas and paragangliomas expressed,
      with 2 exceptions, only the c-src and the c-srcNI+NII mRNA species. To assess
      whether neuroblastomas display adrenal chromaffin characteristics, they were
      analysed regarding expression of the chromaffin marker enzyme, phenylethanolamine
      N-methyl transferase. Whereas phaeochromocytomas were positive, all
      neuroblastomas were immuno-chemically negative for this enzyme. These results and
      the c-src expression profile suggest that neuroblastomas, including those with an
      adrenal location, do not originate from the adrenal chromaffin differentiation
      lineage. The data further suggest neuronal c-srcNI mRNA as a marker for
      sympathetic neuronal cells of the sympatho-adrenal lineage.

PMID- 7529212
TI  - New short-chain analogs of a substance-P antagonist inhibit proliferation of
      human small-cell lung-cancer cells in vitro and in vivo.
AB  - Human small-cell lung-cancer cells (SCLC) produce and secrete gastrin-releasing
      peptide (GRP), the mammalian equivalent of bombesin (BN). There is some evidence
      to suggest that GRP is an autocrine regulator of SCLC cell growth. In the search
      for potent BN antagonists, several substance-P (SP) analogs were found to inhibit
      the growth of SCLC cells. We found that a known short-chain SP antagonist, pHOPA
      DTrp-Phe-DTrp-Leu-Leu-NH2(NY3238), inhibits the binding of 125I-Tyr4-BN on Swiss
      3T3 cell line expressing BN receptors, as well as the proliferation of NCI-H69
      SCLC cells. In this study we tested several analogs of NY3238 and we found that
      NY3521 and NY3460 are more effective in inhibition of proliferation of SCLC cells
      but less potent in inhibition of binding of 125I-Tyr4-BN on Swiss 3T3 cells than
      NY3238. Furthermore, we detected specific binding of radiolabelled NY3238 even
      below 1 nM on NCI-H69 cells that could have been inhibited by SP and NY3460
      rather than by BN. In addition to these in vitro studies, NY3460 proved to be
      effective in inhibiting the growth of NCI-H69 SCLC xenografts in nude mice in
      vivo. These analogs of NY3238 could be promising therapeutic agents in the
      treatment of SCLC.

PMID- 7529213
TI  - Role of tumor-derived fibroblasts in the growth of primary cultures of human
      breast-cancer cells: effects of epidermal growth factor and the somatostatin
      analogue octreotide.
AB  - In the present study we have investigated the role of human breast-cancer-derived
      fibroblasts in the proliferation of primary cultures of epithelial cells derived
      from the same tumor. For this purpose, a co-culture system, using Transwell
      tissue-culture inserts with microporous membranes was employed. Fibroblasts and
      epithelial cells were enriched according to differences in their density on
      Percoll density gradients. The co-culture system was first established using MCF
      7 breast cancer cells and a human fibroblast line (HF cells). Insulin, 17 beta
      estradiol, EGF and HF cells all significantly stimulated the growth of MCF-7
      breast cancer cells. The stimulatory effects of insulin, E2 and EGF were additive
      to the stimulatory effect of HF cells. These data suggest that (unique)
      factor(s), other than the above-mentioned growth-promoting compounds, are
      responsible for the growth-promoting effects of fibroblasts. In half of the human
      breast cancers investigated, tumor-derived fibroblasts stimulated tumor-derived
      epithelial cell proliferation. EGF significantly stimulated epithelial cell
      proliferation in 4 out of 6 cultures. The stimulatory effects of fibroblasts and
      EGF were additive or synergistic, and were observed in the additional presence of
      FCS, again suggesting production of unique factor(s) by the fibroblasts. In one
      culture the fibroblasts significantly inhibited epithelial tumor-cell
      proliferation. Conversely, the epithelial cells significantly stimulated
      proliferation of fibroblasts in 3 out of 3 cultures. The somatostatin analogue
      octreotide significantly inhibited epithelial cell proliferation by 46% in one
      tumor-cell culture in the absence, but not in the presence, of fibroblasts. In
      one culture, octreotide significantly inhibited the proliferation of fibroblasts
      co-cultured with epithelial cells.

PMID- 7529214
TI  - Signal-averaged ECG in prediction of the short-term suppression of ventricular
      premature beats by Mexiletine.
AB  - We analyzed whether baseline parameters of time-domain and spectrotemporal
      analysis of a signal-averaged ECG or their changes during Mexiletine therapy can
      predict the antiarrhythmic efficacy of the drug. On 60 post-MI patients with >
      100 ventricular premature beats per hour, signal-averaged ECGs were recorded
      before and after a constant infusion of Mexiletine (7 mg/kg) for 1 h and again
      after 4 days of oral Mexiletine therapy (Mexiletine SR, 360 mg twice daily).
      Spectrotemporal analysis was performed on a fixed analyzed signal duration of QRS
      complex and ST-segment of X-, Y-, Z-leads using the temporal window of the
      rectangular type, measuring signals between 10-20 Hz. Intravenous and oral
      Mexiletine did not produce significant changes in mean values of any time-domain
      parameters. However, using informative variables of spectra of the signal
      averaged ECG, we managed retrospectively to predict antiarrhythmic efficacy in
      92% of the patients. Only certain frequency bands (from the range of the spectra
      at baseline, 10-120 Hz) were predictive for intravenous Mexiletine efficacy: 40
      55 Hz in lead Y (P = 0.0116); 55-70 Hz in leads X and Z (P = 0.0063 and P =
      0.0269, respectively); 70-85 Hz in lead Z, (P = 0.0227). When the treatment with
      intravenous Mexiletine was effective, the baseline power spectrum density was
      lower than when the drug was ineffective, and vice versa. Moreover, the efficacy
      of oral Mexiletine can be predicted by power density spectrum at baseline (10-25
      Hz in lead Z, P = 0.0210; 70-85 Hz in lead Y, P = 0.0254) and by one of the
      possible (increased, decreased, unchanged) effects of intravenous Mexiletine on
      the spectra at frequency bands (70-85 Hz in lead X, P = 0.0432 and 40-120 Hz in
      lead Z, P = 0.0156). These results show the value of spectrotemporal signal
      averaged ECG in selecting a subgroup of post-myocardial infarction patients that
      may benefit from Mexiletine therapy.

PMID- 7529217
TI  - Natural history of hepatitis C.
AB  - With advances in tools for the diagnosis of hepatitis C virus (HCV) infection, it
      has become easier to evaluate the natural course of hepatitis C. Although HCV
      infection initially occurs in adult individuals, in most patients with acute
      hepatitis C (68%) it develops into chronic hepatitis. Once chronic hepatitis is
      established, the rate of spontaneous cure of the liver disease is very rare
      (below 2%). The duration from the onset of acute hepatitis until the time of
      diagnosis of cirrhosis of the liver and of hepatocellular carcinoma is about 20
      and 30 years, respectively. The long-term clinical course of hepatitis C is
      divided into the three phases of acute, silent, and reactivated. The acute phase
      lasts from the onset of disease until 2-3 years thereafter, and the silent phase
      which follows lasts for 10-15 years. In the silent phase, the serum transferase
      level remains relatively low, below 100 IU/l, and is sometimes within the normal
      range. In the reactivated phase, the level of serum aminotransferase increases
      and remains at a high or moderate level until hepatocellular carcinoma develops.
      The mechanism of the chronicity of hepatitis C is unknown. However, recent
      advances in molecular analysis may soon elucidate this. Successive antigenic
      change of the HCV E2/NS1 hypervariable domain as a result of mutations may
      represent a mechanism by which this virus escapes the host immunosurveillance
      system, as well as a mechanism of its chronicity.

PMID- 7529215
TI  - Evaluation of toxicity and efficacy of a combination of antineoplastic agents in
      the prevention of PVR.
AB  - The retinal toxicity of a combination of antineoplastic drugs in free and
      liposome-encapsulated form was determined in the rabbit eye. Bleomycin sulfate
      and 5-fluorouridine were evaluated by clinical observation, electroretinogram,
      and histological study. Forty-five eyes were injected with combinations of
      various doses of bleomycin and 5-FUR in free and encapsulated form; 10 eyes
      served as controls. The nontoxic free dose was found to be 3.5 micrograms
      bleomycin and 150 micrograms 5-FUR. Liposome encapsulation increased the nontoxic
      dose to 4.7 micrograms bleomycin and 200 micrograms 5-FUR. Four groups of rabbits
      in which proliferative vitreoretinopathy had been induced were used for the
      efficacy study; the control group received an injection of PBS; the second group
      was injected with a combination of 3.5 micrograms bleomycin and 150 micrograms 5
      FUR in free form; the third group was injected with the identical doses in
      liposome-encapsulated form; and the fourth group received encapsulated bleomycin
      (4.7 micrograms) and 5-FUR (200 micrograms). The dose used in Group 4 was
      significantly more effective (P < 0.01) in preventing tractional retinal
      detachment and marginally more effective (P = 0.054) in preventing
      neovascularization.

PMID- 7529218
TI  - The role of hepatitis C virus in hepatocellular carcinoma in Japan.
AB  - Increasing numbers of patients with hepatocellular carcinoma (HCC) have been
      reported in Japan. In this paper, we investigated the role of hepatitis C virus
      (HCV) in HCC and the reason for the increase, using patients admitted to our
      university hospital from 1945 to 1992. 99 (73%) of 135 patients with HCC were
      positive for anti-HCV. Prospective studies demonstrated that 22 of 158 (14%)
      patients with chronic hepatitis C, and 31 of 70 (44%) cirrhotic patients with
      anti-HCV developed to HCC during the follow-up period (10.1 +/- 3.3 and 7.3 +/-
      3.5 years, respectively). Prolonged survival of cirrhotic patients during past
      decades would also contribute to the increasing number of HCC cases as well as
      the number of HCV infections in Japan.

PMID- 7529216
TI  - Biomicroscopy and fluorescein angiography of pigmented iris tumors. A
      retrospective study on 44 cases.
AB  - The classification of pigmented iris tumors is a difficult clinical problem.
      Based on the retrospective observation of colour photographs and iris angiograms
      of 44 pigmented iris tumors observed over 19 years, the authors present an
      original grading scheme with scores depending on both the biomicroscopical and
      the fluoroiridographic patterns of the tumors. The biomicroscopical parameters
      considered were: thickening of the iris in the area of tumor, pupillary
      distortion and/or ectropion uveae and uneven pigment density. The
      fluoroiridographic parameters were: early visibility of the anomalous tumoral
      network, hyperfluorescence inside or around the tumor, and dye leakage at sites
      remote from the mass. Based on the score of each tumor, the 44 cases were divided
      into 3 groups with the different degrees of malignancy confirmed by either
      histological examination or by follow-up behaviour. The authors suggest that
      routine use of biomicroscopic-fluoroiridographic classification of pigmented iris
      tumors would be useful.

PMID- 7529219
TI  - Characterization of HCV structural proteins expressed in various animal cells.
AB  - Hepatitis C virus (HCV) is a main causative agent for transfusion-associated and
      sporadic cases of non-A, non-B hepatitis throughout the world. HCV has a positive
      strand RNA of about 9,400 nucleotides as its genome, whose organization is
      similar to those of animal pestiviruses or human flaviviruses. In spite of the
      lack of an effective replication system in tissue culture cells, genes coding for
      viral proteins of HCV have been identified. The putative nucleocapsid (p22) and
      envelope (gp35 and gp60) proteins have been expressed in cells by different
      vectors under various foreign promoters. Furthermore, a truncated core protein
      and association of envelope proteins with nonstructural proteins have also been
      observed. These synthesized viral proteins have been shown to be useful for
      diagnostic assays.

PMID- 7529220
TI  - Pathology of hepatitis C.
AB  - Damage and necrosis of hepatocytes in viral hepatitis C is considered to be
      immune mediated as in hepatitis B. Hepatocellular necrosis accompanies
      infiltration of lymphocytes and this feature, called necroinflammation,
      characterizes all types of viral hepatitis and corresponds to the histological
      expression of hepatitis. Although the histological features of hepatitis C do not
      differ fundamentally from those of hepatitis B, there are some quantitative
      differences. Weak but constant necroinflammation and a strong lymphocytic
      reaction of the portal tracts appear to be relatively unique to chronic hepatitis
      C. Nearly all chronic hepatitis C cases do not improve during the natural course
      of infection; however, in a limited number of cases, interferon treatment can
      eliminate the virus leading to normalization. The pattern and extent of fibrosis
      can roughly predict the efficacy of interferon treatment.

PMID- 7529221
TI  - Diagnosis of hepatitis C.
AB  - As indicators to determine the diagnosis, condition, and prognosis of hepatitis
      C, methods have been developed such as the detection of HCV-RNA by the nested RT
      PCR method, quantitative assay of HCV-RNA by the competitive RT-PCR method,
      qualitative and quantitative assay of various anti-HCV IgG and IgM antibodies,
      and identification of viral type (genotype and serological group). The clinical
      utility of these HCV markers in early diagnosis and prognosis of acute hepatitis
      C, for differentiating it from acute flare in HCV carriers, and in distinguishing
      between past and current infection in second-generation-anti-HCV-positive
      patients with normal serum alanine aminotransferase has been evaluated.

PMID- 7529222
TI  - Current state of interferon therapy for chronic hepatitis C.
AB  - The current status of interferon (IFN) therapy in chronic hepatitis C is
      presented, focusing on the results of studies in Japan. Depending on the IFN
      treatment regimen used in chronic hepatitis C, it is possible to eradicate HCV in
      a relatively high percentage of patients (about 40%) and to achieve a cure for
      chronic hepatitis C. The objective of treatment should therefore be the
      eradication of HCV. The efficacy of IFN in chronic hepatitis C is dependent on
      the dosage of IFN, duration of treatment, liver histology findings, serum HCV-RNA
      levels, and HCV genotype. Besides a flu-like syndrome, many adverse reactions are
      associated with high-dose, long-term IFN treatment. However, as a rule, full
      recovery or improvement follows prompt withdrawal of IFN. By modification of the
      IFN, it will be possible to reduce adverse reactions and to create a more
      effective IFN to further enhance the effect of IFN in chronic hepatitis C.

PMID- 7529223
TI  - Spontaneous regression of metastatic renal cell carcinoma following palliative
      irradiation of the primary tumour.
AB  - A 58 years old man presented with a bulky renal primary tumour, paratracheal
      lymphadenopathy and multiple pulmonary metastases. Spontaneous regression of
      intrathoracic metastases occurred after low dose palliative irradiation of the
      primary tumour. Serum levels of Interleukin-2 receptor were elevated during the
      period of tumour regression but concentrations of other cytokines were normal.
      Progressive abdominal disease eventually caused death. Autopsy confirmed the
      presence of renal cell carcinoma with intrathoracic metastases.

PMID- 7529224
TI  - Postextrasystolic transient contractile alternans in canine hearts.
AB  - We found that postextrasystolic potentiated contractility after a spontaneous
      extrasystole most frequently decayed as a transient alternans over several beats
      in excised, cross-circulated, atrially paced canine hearts. This type of heart
      preparation; which we have been using consistently in mechanoenergetic studies,
      had normal coronary blood perfusion pressure as well as flow and mechanoenergetic
      performance. Spontaneous atrial and ventricular extrasystoles occurred
      occasionally in every heart. Arrhythmic changes in left ventricular (LV) pressure
      at a fixed volume reflected corresponding changes in contractility. We analyzed
      nearly 3,600 cases of postextrasystolic potentiation in 68 hearts; 84% decayed as
      transient alternans, 6% decayed exponentially, and 10% belonged to neither type.
      We found that a postextrasystolic compensatory pause always preceded the
      transient alternans after either an atrial or ventricular extrasystole at any
      constant atrial pacing rate (85-188 beats/min). The decay was either exponential
      or nonalternating when the pause did not exist after an atrial extrasystole
      during occasional pacing failure. Therefore, the compensatory pause after either
      an atrial or ventricular extrasystole seems essential for the postextrasystolic
      transient alternans of LV contractility in the type of canine heart preparation
      we have been using.

PMID- 7529225
TI  - Metabolism of polychlorinated phenols by Pseudomonas cepacia AC1100:
      determination of the first two steps and specific inhibitory effect of
      methimazole.
AB  - Resting cells of 2,4,5-trichlorophenoxyacetic acid-grown Pseudomonas cepacia
      AC1100 metabolize both dichlorophenols, such as 2,4-dichlorophenol, 2,6
      dichlorophenol, 3,4-dichlorophenol, and 3,5-dichlorophenol, and more highly
      substituted phenols, such as 2,4,6-trichlorophenol and pentachlorophenol, to the
      corresponding chlorohydroquinones. The first hydroxylation occurs in the para
      position of the phenol regardless of whether this position is replaced by a
      chlorine substituent. The first evidence leading to the characterization of para
      hydroxylase as a flavin-containing enzyme is provided by the inhibitory effect of
      methimazole, an alternate substrate for this monooxygenase, on the degradative
      ability of the strain. In a second step, with tetrachlorohydroquinone,
      trichlorohydroxyquinone was isolated and completely characterized.
      Trichlorohydroxyquinone was also obtained from tetrachloroquinone. Incubation of
      the cells in the presence of an external source of NADPH prevents the further
      degradation of tetrachlorohydroquinone, suggesting that the quinone derived from
      the two-electron oxidation of the hydroquinone is more likely the substrate for
      the second hydroxylation.

PMID- 7529226
TI  - Diminished expression of insulin-like growth factor (IGF) binding protein-5 and
      activation of IGF-I-mediated autocrine growth in simian virus 40-transformed
      human fibroblasts.
AB  - The reduced growth factor requirements of murine fibroblasts transformed by
      simian virus 40 (SV 40) have been attributed to insulin-like growth factor (IGF)
      I induction by T antigen and consequent activation of IGF-I receptor signaling.
      The present study shows that the autonomous growth of SV 40-transformed human
      fibroblasts also requires type-I IGF-I receptor activation but that this is not
      due to de novo induction of IGF-I gene expression since untransformed human
      fibroblasts, which fail to proliferate in the absence of serum, also showed IGF-I
      gene expression under serum-free conditions. DNA synthesis assays confirmed that
      untransformed cells were responsive to exogenous IGF and indicated that
      transformed cells were already maximally stimulated. In untransformed
      fibroblasts, IGF binding was principally to abundant membrane-associated IG-FBP
      5, whereas in transformed fibroblasts this protein was minimally expressed, and
      IGF binding was to IGF receptors. Loss of detectable membrane-associated IG-FBP-5
      in transformed cells was associated with diminished IGFBP-5 gene expression and
      with loss of IGF-II gene expression. Exogenous IGFBP-5 associated with the
      membranes of transformed cells and inhibited the autocrine growth of these cells.
      These findings suggest that loss of IGFBP-5 in SV 40-transformed fibroblasts
      facilitates interaction of endogenously produced IGF-I with the IGF-I receptor
      and increases their sensitivity to autocrine stimulation.

PMID- 7529227
TI  - Oxidized low-density lipoprotein decreases the expression of endothelial nitric
      oxide synthase.
AB  - The atherogenic effects of low-density lipoprotein (LDL) may be mediated, in
      part, by its effect(s) on endothelial-derived nitric oxide (NO). To determine
      whether LDL can modulate NO production by changing NO synthase expression, we
      treated human saphenous vein endothelial cells with increasing concentrations of
      native or oxidized LDL (0-100 micrograms/ml) for various durations (0-72 h).
      Oxidized, but not native LDL caused a time-dependent decrease in steady-state NO
      synthase mRNA levels. This coincided with a maximal 56% decrease in NOS activity
      was determined by [3H]arginine to [3H]citrulline conversion. In the presence of
      actinomycin D, treatment with oxidized LDL reduced the half-life of NO synthase
      mRNA from 36 to 10 h. This decrease in NO synthase mRNA correlated with the
      degree of LDL oxidation and was attenuated by pretreatment with cycloheximide.
      Nuclear run-off studies showed a biphasic transcriptional pattern of NO synthase
      gene with an initial 25% decrease during the first 6 h followed by a maximal 2.2
      fold increase over baseline during the subsequent 18 h. These results indicate
      that oxidized LDL regulates endothelial NOS expression through a combination of
      early transcriptional inhibition and post-transcriptional mRNA destabilization.

PMID- 7529228
TI  - Strand transfer mediated by human immunodeficiency virus reverse transcriptase in
      vitro is promoted by pausing and results in misincorporation.
AB  - Human immunodeficiency virus (HIV-1) is able to recombine by transfer of the
      growing DNA strand from internal regions of one genome to another. The strand
      transfer reaction, catalyzed by HIV-1 reverse transcriptase (RT), was conducted
      in vitro between donor and acceptor RNA templates that were derived from natural
      HIV-1 nef genes. The donor and acceptor templates shared a nearly homologous
      region where strand transfer could occur, differing only in that the acceptor had
      a 36-nucleotide insertion and 6 widely spaced base substitutions compared with
      the donor. We sequenced elongated primers that underwent transfer. The position
      of transfer was revealed by the change of sequence from that of the donor to that
      of the acceptor. Results showed a positive correlation between positions where
      the RT paused during synthesis and enhancement of strand transfer. Elimination of
      a pause site, with a minimal change in sequence, decreased the frequency of
      strand transfer in the immediate area. Analysis of the sequence of DNA products
      resulting from transfer at a frequently used site showed that mutations had been
      introduced into the DNA at about the point of transfer. Remarkably, approximately
      30% of the products contained mutations. Base substitutions, short additions and
      deletions were observed. Mutations did not appear in DNA products extended on the
      donor template without transfer. The identity of the mutations suggests that they
      were caused by a combination of slippage and non-template-directed nucleotide
      addition. These results indicated that the detected mutations were related to the
      process of strand transfer.

PMID- 7529229
TI  - The release of fibroblast growth factor-1 from NIH 3T3 cells in response to
      temperature involves the function of cysteine residues.
AB  - Fibroblast growth factor (FGF)-1 is released from NIH 3T3 cells in response to
      heat shock as a biologically inactive protein that is unable to bind heparin and
      requires activation by (NH4)2SO4 to generate a biologically active extracellular
      heparin-binding growth factor (Jackson, A., Friedman, S., Zhan, X., Engleka, K.
      A., Forough, R., and Maciag, T. (1992) Proc. Natl. Acad. Sci. USA 89, 10691
      10695). To further study the mechanism of FGF-1 release in response to heat shock
      (42 degrees C), we examined the kinetics of FGF-1 release from FGF-1-transfected
      NIH 3T3 cells and observed that the cells require at least 1 h of exposure to
      heat shock conditions for the release of FGF-1. Interestingly, agents that
      interfere with the function of the endoplasmic reticulum-Golgi apparatus,
      exocytosis, and the multidrug resistance pathway (brefelden A, methylamine, and
      verapamil, respectively) do not inhibit the release of FGF-1 in response to
      temperature; rather, they exaggerate the release of FGF-1. Because immunoblot
      analysis of FGF-1 in the conditioned medium of heat-shocked NIH 3T3 cells
      revealed the presence of a minor band with an apparent molecular weight of a FGF
      1 homodimer and because we have previously shown that FGF-1, but not FGF-2, is
      able to form a homodimer in response to chemical oxidation by CuCl2 (Engleka, K.
      A., and Maciag, T. (1992) J. Biol. Chem. 267, 11307-11315), we examined whether
      reducing agents would substitute for (NH4)2SO4 and activate extracellular FGF-1.
      Indeed, dithiothreitol and reduced glutathione are able to individually generate
      a FGF-1 monomer as a heparin-binding protein from the conditioned medium of heat
      shocked NIH 3T3 cell transfectants. To confirm that cysteine residues are
      involved in the release of FGF-1 in response to temperature, we used mutagenesis
      to prepare a human FGF-1 Cys-free mutant in which Cys30, Cys97, and Cys131 were
      converted to serine. Analysis of the release of the FGF-1 Cys-free mutant in NIH
      3T3 cells transfected with the FGF-1 Cys-free mutant demonstrated that the FGF-1
      Cys-free mutant is not released into the conditioned medium in response to
      temperature. Interestingly, exposure of the NIH 3T3 cell FGF-1 Cys-free
      transfectants to brefelden A followed by heat shock also demonstrated the absence
      of the extracellular FGF-1 Cys-free mutant.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7529230
TI  - SH3 domains specifically regulate kinase activity of expressed Src family
      proteins.
AB  - The Src homology 2 (SH2) and Src homology 3 (SH3) domain are approximately 50%
      conserved in various Src family kinase members. Several lines of evidence suggest
      that in Src these domains are sequence motifs that direct substrate recognition,
      regulate kinase activity, or control subcellular localization. We sought to
      investigate the function of the homology domains in human Lyn, and to determine
      whether the differences between various SH3 domains affect function. To do this,
      we generated variant forms of Lyn lacking SH2 and SH3 domains, and created
      chimeras in which the SH3 domains in human c-Src and Lyn were replaced with SH3
      domains from other family members. In contrast to similar deletions in Src, forms
      of Lyn lacking SH2 or SH3 had decreased kinase activity. The SH3 chimeras all had
      individual characteristics. Insertion of the Blk SH3 domain into Lyn restored
      kinase activity, while insertion of the Fyn or Src SH3 into Lyn enhanced the
      kinase activity 2-3-fold. Insertion of the Lyn SH3 into Src also doubled kinase
      activity. Expression of the Lyn-Src SH3 chimera in mammalian cells induced cell
      transformation. This study 1) demonstrates that the regulation of Lyn is
      different than Src, and 2) provides new evidence that despite their homology,
      there are important functional differences between the SH3 domains of the various
      Src family members.

PMID- 7529231
TI  - A region of human CD14 required for lipopolysaccharide binding.
AB  - CD14, a glycosylphosphatidylinositol-anchored protein on the surface of
      monocytes, macrophages, and polymorphonuclear leukocytes, is a receptor for
      lipopolysaccharide (LPS). CD14 binding of LPS is enhanced by serum proteins,
      especially lipopolysaccharide binding protein. The serum-dependent binding of LPS
      to CD14 stimulates macrophages to make cytokines, which can cause septic shock in
      humans and animals. Here, we identify a region in human CD14 which is important
      in serum-dependent LPS binding and LPS-induced cellular activation. Four small
      regions (4-5 amino acids long) within the N-terminal 65 amino acids of CD14 were
      deleted singly or in combination. The deletion mutants were stably expressed in
      Chinese hamster ovary (CHO) cells. The mutants were characterized in three
      assays: reactivity with anti-CD14 monoclonal antibody, serum-dependent LPS
      binding, and LPS-induced activation of NF-kappa B. Some of the mutants
      selectively lost reactivity with the anti-CD14 monoclonal antibody that inhibited
      serum-dependent LPS binding and cellular activation. All of the mutants bound
      much less LPS than wild type CD14 in the presence of serum. None of the mutants
      bound more LPS than control CD14-CHO cells in the absence of serum. CD14-CHO
      cells respond to LPS by activation of NF-kappa B. All of the deletion mutants
      were less active LPS receptors than wild type CD14-CHO cells. The delta AVEVE
      mutant, the delta DDED and delta PQPD double mutant, and the delta DDED, delta
      PQPD, delta AVEVE, and delta DPRQY quadruple deletion mutants were essentially
      inactive LPS receptors in CHO cells. These studies suggest that the 65 N-terminal
      amino acids of CD14 are critical for serum-dependent binding of LPS to CD14 and
      subsequent signal transduction in CHO cells.

PMID- 7529232
TI  - Ligand binding by the immunoglobulin superfamily recognition molecule CD2 is
      glycosylation-independent.
AB  - The evolutionary success of the immunoglobulin superfamily (IgSF) is thought to
      reflect the ability of IgSF protein domains to form stable structural units. The
      role of glycosylation in stabilizing these domains is controversial, however. In
      this study a systematic analysis of the effect of glycosylation on the ligand
      binding properties of the cell-cell recognition molecule CD2, which consists of
      two IgSF domains, was undertaken. A form of human soluble CD2 (hsCD2) with single
      N-acetylglucosamine residues at each glycosylation site was produced by
      inhibiting glucosidase I with N-butyldeoxynojirimycin during expression in
      Chinese hamster ovary cells and digesting the expressed hsCD2 with
      endoglycosidase H. The ligand and antibody binding properties of this form of
      hsCD2 were indistinguishable from those of fully glycosylated hsCD2 as determined
      by surface plasmon resonance analyses. The protein also formed diffraction
      quality crystals and analysis of the 2.5-A resolution crystal structure indicated
      that the single N-acetylglucosamine residue present on domain 1 is unlikely to
      stabilize the ligand binding face of hsCD2. A second, fully deglycosylated form
      of hsCD2 also bound the ligand and antibodies although this form of the protein
      tended to aggregate. In contrast to the results of previous studies, the current
      data indicate that the structural integrity and ligand binding function of human
      CD2 are glycosylation-independent.

PMID- 7529233
TI  - Transforming growth factor-beta regulates collagen gel contraction by increasing
      alpha 2 beta 1 integrin expression in osteogenic cells.
AB  - The contraction of floating collagen gels is suggested to mimic the
      reorganization of collagenous matrix during development and tissue healing. Here,
      we have studied two osteogenic cell lines, namely MG-63 and HOS, and a chemically
      transformed subclone of HOS cells, HOS-MNNG. Transforming growth factor-beta (TGF
      beta), a putative regulator of bone fracture healing, increased collagen gel
      contraction by MG-63 and HOS-MNNG, but not by HOS cells. Our data show that TGF
      beta-induced fibronectin synthesis is not sufficient for the process. Instead,
      anti-beta 1 integrin antibodies could prevent the contraction. There are three
      different integrin heterodimers that are known to mediate the cell-collagen
      interaction, namely alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1. In MG-63
      cells TGF-beta increased the expression of alpha 2 beta 1 integrin and decreased
      the expression of alpha 3 beta 1 integrin, whereas alpha 1 beta 1 integrin is not
      expressed. HOS cells had no alpha 2 beta 1 integrin, neither did TGF-beta induce
      its expression. However, HOS-MNNG cells expressed more alpha 2 beta 1 integrin
      when treated with TGF-beta. Thus, we suggest that the mechanism of the enhanced
      collagen gel contraction by TGF-beta is the increased expression of alpha 2 beta
      1 integrin heterodimer. To further test this hypothesis, we expressed a full
      length alpha 2 integrin cDNA in HOS cells and in MG-63 cells. We obtained HOS
      cell clones that expressed alpha 2 beta 1 heterodimer, and the ability of these
      cells to contract collagen gels was greatly enhanced. Furthermore, the
      contraction by MG-63 cells transfected with alpha 2 integrin cDNA was enhanced,
      and the contraction by cells transfected with antisense oriented alpha 2 integrin
      cDNA was decreased. Thus, both in MG-63 and HOS cells the increased alpha 2
      integrin expression alone was sufficient for the enhanced contraction of collagen
      gels. Furthermore, the amount of alpha 2 integrin is critical for the process,
      and its decrease leads to diminished ability to contract gels.

PMID- 7529234
TI  - Self-association of the "death domains" of the p55 tumor necrosis factor (TNF)
      receptor and Fas/APO1 prompts signaling for TNF and Fas/APO1 effects.
AB  - Signaling by the p55 tumor necrosis factor (TNF) receptor and by the structurally
      related receptor Fas/APO1 is initiated by receptor clustering. Data presented
      here and in other recent studies (Wallach, D., Boldin, M., Varfolomeev, E. E.,
      Bigda, Y., Camonis, H.J. and Mett, I. (1994) Cytokine 6, 556; Song, H.Y., Dunbar,
      J.D., and Bonner, D.B. (1994) J. Biol. Chem. 269, 22492-22495) indicate that part
      of that region within the intracellular domains of the two receptors that is
      involved in signaling for cell death, as well as for some other effects (the
      "death domain", specifically self-associates. We demonstrate also the expected
      functional consequence of this association; a mere increase in p55 TNF receptor
      expression, or the expression just of its intracellular domain, is shown to
      trigger signaling for cytotoxicity as well as for interleukin 8 gene induction,
      while expression of the intracellular domain of Fas/APO1 potentiates the
      cytotoxicity of co-expressed p55 TNF receptor. These findings indicate that the
      p55 TNF and Fas/APO1 receptors play active roles in their own clustering and
      suggest the existence of cellular mechanisms that restrict the self-association
      of these receptors, thus preventing constitutive signaling.

PMID- 7529235
TI  - New CD44 splice variants associated with human breast cancers.
AB  - Changes in the CD44 variant (CD44v) isoforms on the cell surface have been
      correlated with tumor metastasis. In this study we have examined the expression
      of CD44 variant isoforms in human breast carcinoma samples by a variety of
      techniques including immunohistochemistry, reverse transcriptase-polymerase chain
      reaction (RT-PCR), and nucleotide sequencing. Using RT-PCR, we have determined
      that normal human breast tissue contains primarily the CD44 epithelial (CD44E)
      form and very little CD44 standard (CD44s) form. However, metastatic breast
      carcinomas appear to overexpress both the CD44E and CD44s forms and also display
      multiple new species of CD44 variant isoforms. Histocytochemical staining using
      anti-CD44 antibody (recognizing a common determinant of the CD44 class of
      glycoproteins) confirms that the CD44 molecules are overexpressed and
      preferentially located in metastatic breast cancer tissues. Nucleotide sequencing
      analyses indicate that at least four new CD44 variant isoforms (i.e., displaying
      unique splicing via the insertion or the deletion of exons 7, 10, 11, and 14) may
      be closely associated with human metastatic breast cancers. These newly described
      CD44 variant isoforms may be useful for monitoring the progression of human
      breast cancer metastasis.

PMID- 7529236
TI  - Chloride is required for receptor-mediated divalent cation entry in mesangial
      cells.
AB  - Agonists which stimulate the inositol 1,4,5 trisphosphate ([1,4,5]-IP3)-dependent
      mobilization of Ca2+ from intracellular stores also stimulate entry of divalent
      cations across the cell membrane. Under appropriate experimental conditions,
      divalent cation entry across the cell membrane can be monitored as the rate at
      which the intracellular fluorescence of divalent cation indicators is quenched by
      the addition of Mn2+ to the extracellular medium. We report that addition of
      vasopressin to fura-2-loaded glomerular mesangial cells in culture markedly
      accelerated the rate at which Mn2+ quenched fura-2 fluorescence at its Ca(2+)
      insensitive wavelength in the presence of extracellular NaCl, but that this
      quench response was attenuated when Cl- was removed from the extracellular medium
      by equimolar substitution with impermeant anions (gluconate, methanesulfonate,
      acetate, lactate). Similarly, loss of agonist-induced quench also occurred when
      Cl- was substituted with gluconate in K(+)-containing media. Addition of the Cl-
      channel inhibitor, 5-nitro-2-(3-phenylpropylaminobenzoic acid) (NPPB), also
      inhibited Mn(2+)-induced quench of fura-2 fluorescence following vasopressin
      addition. In contrast, in the presence of gramicidin to provide an alternate
      conductance pathway to accompany divalent cation entry, agonist-dependent Mn2+
      quench occurred even in the absence of extracellular Cl-, indicating that the
      requirement for Cl- was not the result of cotransport on a common transporter nor
      the result of Cl- serving as a necessary cofactor for divalent cation entry. A
      similar dependence on extracellular Cl- was observed for other Ca(2+)-mobilizing
      agonists such as endothelin, as well as the intracellular Ca2+ ATPase inhibitor,
      thapsigargin. Extracellular Cl- dependence for agonist-induced divalent cation
      entry was also reflected in a corresponding extracellular Cl- dependence for
      agonist-induced mesangial cell contraction. It has been previously shown by
      ourselves (Kremer et al., 1992a, Am. J. Physiol., 262:F668-F678) and others that
      agonist-stimulated calcium mobilization in mesangial cells is accompanied by
      inhibition of K+ conductance and increased Cl- conductance. Accordingly, we
      conclude that the current findings suggest that activation of Cl- conductance
      provides regulated charge compensation for receptor-mediated divalent cation
      entry in response to Ca(2+)-mobilizing vasoconstrictor agonists in mesangial
      cells.

PMID- 7529237
TI  - Insulin-like growth factor II regulation of gene expression in rat and human
      hepatomas.
AB  - Insulin-like growth factor II (IGF II) regulated tissue-specific gene expression
      in hepatoma cell lines, but had no effect on expression of tissue-specific genes
      in primary cultures of E14 and newborn rat liver cells depleted of erythroid
      cells. No change was observed in these primary cultures with respect to alpha
      fetoprotein (alpha-FP), albumin, cytokeratin 19 (CK19), gamma
      glutamyltranspeptidase (GGT), and IGF II receptors. Two well-differentiated
      hepatoma, HepG2 and FTO-2B, and a poorly differentiated hepatoma, H4AzC2, did not
      show increased proliferation in the presence of IGF II, yet showed gene
      expression changes in response to IGF II. In HepG2 cells, IGF II increased
      albumin mRNA levels and resulted in a shift from clusters of cells positive to
      100% of the cells expressing immunohistochemically detectable albumin. The
      transcription factor HNF-3 beta mRNA and protein levels of the bile duct markers,
      CK19 and GGT, were also increased in the presence of IGF II. Other genes tested
      were not affected, including alpha-1-antitrypsin, and two liver-specific
      transcription factors, HNF-4 and HNF-3 alpha. In FTO-2B cells, IGF II increased
      the expression of albumin, CK19, and GGT, without accompanying changes in albumin
      and GGT mRNAs. In H4A7C2 cells, IGF II reduced CK19 and OC.3 protein levels and
      GGT, transferrin, and HNF-3 beta mRNAs. The effects of IGF II on H4AZC2 cells
      were not blocked in the presence of an anti-rat IGF II receptor antibody. We
      conclude that IGF II affects tissue-specific gene expression of hepatomas and
      qualitative and quantitative aspects of its influence on the hepatomas is
      dependent on their degree of differentiation.

PMID- 7529238
TI  - Effects of mutations in cAMP-dependent protein kinase on chloride efflux in Caco
      2 human colonic carcinoma cells.
AB  - In order to evaluate the importance of cAMP and cAMP-dependent protein kinase
      (cAMPdPK) in the regulation of chloride efflux via the cystic fibrosis
      transmembrane conductance regulator (CFTR) chloride channel, Caco-2, human
      colonic carcinoma cells were transfected with an expression vector encoding a
      mutant form of regulatory subunit of cAMPdPK under control of the mouse
      metallothionein 1 promoter. Four stable transformants were isolated that
      expressed the mutant subunit in a Zn(2+)-inducible manner and exhibited Zn(2+)
      inducible inhibition of cAMPdPK activity. The parental and transformed Caco-2
      cells were examined for their abilities to regulate chloride efflux in response
      to various secretagogues using a radioactive iodide-efflux assay. In the
      transformants, induction of the protein kinase mutation with ZnSO4 markedly
      decreased chloride efflux in response to forskolin, the 8-(4-chlorophenylthio)
      analog of cAMP, vasoactive intestinal polypeptide, prostaglandin E2 and
      isoproterenol, whereas Zn(2+)-treated parental cells remained responsive to these
      secretagogues. Treatment with carbachol, calcium ionophores or phorbol ester did
      not acutely affect chloride efflux. Together, these studies indicate that cAMP
      and cAMPdPK are essential components of secretagogue-regulated chloride channel
      activity in the Caco-2 cell line. In whole cell patch clamp recordings, induction
      of the cAMPdPK mutation inhibited anionic conductances indicative of the CFTR
      chloride channel, whereas purified catalytic subunit of cAMPdPK, added
      intracellularly, reversed the inhibition. These latter results demonstrate that
      the CFTR chloride channels in the protein kinase-defective transformants are
      normal and that the protein kinase mutation specifically affects their
      regulation, presumably by direct phosphorylation.

PMID- 7529240
TI  - Detection of acid-fast bacilli in concentrated primary specimen smears stained
      with rhodamine-auramine at room temperature and at 37 degrees C.
AB  - Many laboratory workers prefer the rhodamine-auramine method of staining acid
      fast bacilli (AFB) in primary specimen smears rather than carbol fuchsin stains
      because the stain is more readily interpreted and yields greater sensitivity. The
      increasing incidence of AFB infections serves as an impetus to optimize the
      rhodamine-auramine stain. A total of 782 primary smears were evaluated blindly by
      the rhodamine-auramine method at both room temperature and 37 degrees C. Thirty
      five smears (4.5%) were positive for AFB, 30 were positive by both methods, and 5
      were positive at 37 degrees C only. Room temperature staining detected only 85.7%
      of the positive primary smears. Of the 30 smears positive by both methods, 13
      (43.3%) had equal numbers of AFB on both smears, 13 (43.3%) had more AFB on the
      smear stained at 37 degrees C, and 4 (13.3%) had greater numbers of AFB on the
      smear stained at room temperature. No smears were positive only when stained at
      room temperature. The increasing diagnostic emphasis placed on the primary smear
      underscores the importance of optimizing AFB smear methods, and rhodamine
      auramine staining at 37 degrees C enhances the detection of AFB compared with
      conventional staining at room temperature.

PMID- 7529239
TI  - Characterization of PCR-ribotyping for Burkholderia (Pseudomonas) cepacia.
AB  - Ribotyping, a method of genotyping bacterial isolates for epidemiologic study,
      uses rRNA as a probe to detect chromosomal restriction fragment length
      polymorphisms. Although ribotyping is accurate, its utility is limited by the
      labor and time necessary for Southern blot analysis. PCR-ribotyping uses PCR to
      amplify the 16S-23S intergenic spacer region of the bacterial rRNA operon. Length
      heterogeneity in the spacer region has previously been found to be useful as an
      alternative to standard ribotyping in a study of Burkholderia (Pseudomonas)
      cepacia. To further analyze the accuracy of PCR-ribotyping, three groups of
      previously characterized isolates of B. cepacia were investigated. PCR-ribotyping
      grouped 90 isolates recovered from seven well-defined epidemics into the correct
      outbreak group with a mean concordance of 93%. Both standard ribotyping and PCR
      ribotyping separated 15 unrelated isolates into 14 types. In an analysis of 83 B.
      cepacia isolates from chronically colonized cystic fibrosis patients, the
      concordance of PCR-ribotyping with standard ribotyping ranged from 83 to 100%,
      with a mean of 98%. One isolate from a chronically colonized patient had a
      different type by standard ribotyping but was identical to the other isolates
      from this patient by PCR-ribotyping. Thus, PCR-ribotyping is a rapid and accurate
      method for typing B. cepacia and is less labor intensive than standard
      ribotyping.

PMID- 7529241
TI  - Preliminary study using species-specific oligonucleotide probe for rRNA of
      Bilophila wadsworthia.
AB  - Portions of the 16S RNA from a urease-positive Bilophila wadsworthia strain were
      sequenced, and a probe was constructed. The probe was end labeled with [32P]ATP
      and polynucleotide kinase and hybridized on a nylon filter (by dot blot
      hybridization) to the immobilized rRNA of 12 B. wadsworthia strains and eight
      other anaerobic isolates. The probe efficiently hybridized only to the Bilophila
      strains. Cross-reactivity at high RNA levels (2,000 ng) was observed with one
      strain of Bacteroides thetaiotamicron and one strain of Bacteroides fragilis
      (with 10x SET buffer [20x SET buffer is 0.5 M NaCl, 0.03 M Tris, and 2 mM EDTA])
      but was not seen at lower RNA levels or with 5x SET buffer. When tested against
      mixed cultures of aerobic and anaerobic isolates representative of appendiceal
      abscess flora, the probe did not react with mixed cultures containing no
      Bilophila cells and could detect > or = 10(5) Bilophila CFU/ml when the mixture
      was seeded with Bilophila cells. This probe is of potential use in the rapid
      identification of pure isolates and in the direct identification of B.
      wadsworthia in clinical specimens.

PMID- 7529243
TI  - Rapid and sensitive method for detection of hepatitis C virus RNA by using silica
      particles.
AB  - We describe a rapid, sensitive, and economic method for detection of hepatitis C
      virus (HCV) RNA. This method uses silica particles for purification of nucleic
      acid and then a modified reverse transcription-PCR that minimizes the risk of
      contamination and reduces the amount of reagents used. We found purification by
      silica particles to be at least as sensitive and in certain circumstances more
      sensitive than that by traditional phenol-chloroform extraction. This improved
      sensitivity may be due to more efficient recovery of HCV RNA by silica particles.
      HCV RNA appears to bind to silica particles in a saturable fashion, and the
      addition of extraneous nucleic acids (salmon sperm DNA or tRNA) decreases the
      binding in a dose-related fashion. The reverse transcription-PCR is performed by
      using a modified single tube method which further simplifies and reduces the cost
      of this assay. Finally, this method may be applied to clinical specimens such as
      liver tissue.

PMID- 7529242
TI  - Brucella melitensis cell envelope protein and lipopolysaccharide epitopes
      involved in humoral immune responses of naturally and experimentally infected
      sheep.
AB  - Cell envelope fraction (CEF) of Brucella melitensis B115 was used to investigate
      antibody responses of B. melitensis naturally and strain H38 experimentally
      infected sheep by immunoblotting, indirect enzyme-linked immunosorbent assay
      (ELISA) (I-ELISA), and competitive ELISA (C-ELISA) with monoclonal antibodies
      (MAbs). MAbs used were directed to outer membrane proteins with molecular masses
      of 10, 16.5, 19, 25 to 27, 31 to 34, 36 to 38, and 89 kDa; to the heat shock
      protein DnaK, to O-polysaccharide (O-PS) common (C) and M epitopes; and to rough
      lipopolysaccharide (R-LPS) epitopes. In immunoblotting, all infected sheep sera
      tested recognized a large number of protein bands, including the above-cited
      proteins and other proteins for which MAbs have not been defined. The antibody
      response pattern was different from one animal to another, even within the
      experimentally infected sheep which were infected under the same experimental
      conditions. A number of protein bands were recognized by the sheep sera prior to
      experimental infection and by other uninfected sheep sera. The antibody
      reactivity to these antigens and others might explain the nonspecific antibody
      reactivity of sera in I-ELISA with CEF. C-ELISA confirmed also the individual
      variability of the antibody responses of infected sheep to protein antigens.
      Antibody responses to O-PS C and M epitopes were detected in all experimentally
      infected sheep and in half of the naturally infected sheep, but these responses
      were also heterogeneous in relation to their intensities. Antibody responses to R
      LPS epitopes detected by use of C-ELISA with the anti-R-LPS MAbs were low or
      negative in most of the infected animals. Despite antibody response heterogeneity
      for CEF antigens, immunoblot and C-ELISA results indicated that, among the CEF
      antigens, the O-PS epitopes (C and M epitopes) and epitopes of the major 25- to
      27- and 31- to 34-kDa outer membrane proteins seem to be the most promising for
      detecting B. melitensis infection in sheep.

PMID- 7529244
TI  - Performance of third-generation confirmatory tests for detection of antibody to
      hepatitis C virus.
AB  - We investigated three immunoblot assays (RIBA 3.0 from Chiron, Matrix from Abbott
      Laboratories, and LiaTek III from Organon Teknika) for the detection of antibody
      to hepatitis C virus. RIBA 3.0 and Matrix require reactivity to two antigens and
      LiaTek III requires reactivity to one for a sample to be positive. We tested 80
      samples that were positive in repeat enzyme immunoassays by supplemental tests.
      The results showed that 55, 46, and 28% were reactive by LiaTek III, RIBA 3.0,
      and Matrix, respectively; 54, 33, and 13% of the samples were indeterminate by
      Matrix, RIBA 3.0, and LiaTek III, respectively. There were 32, 21, and 16%
      nonreactive samples by LiaTek III, RIBA 3.0, and Matrix, respectively. Of the
      samples positive by RIBA 3.0, only 50 and 76% were reactive by Matrix and LiaTek
      III, respectively. A large number of samples that were indeterminate by RIBA 3.0
      were positive by LiaTek III (52%). The core antigen was the most reactive antigen
      in all three tests (48 to 57%). The NS4 antigen in Matrix (20%) and LiaTek III
      (16%) was poorly reactive, although it performed better in RIBA 3.0 (45%). The
      NS5 and E2/NS1 antigens made minor contributions to reactivity. The combinations
      of the core, NS3, and NS4 antigens produced 77% of the RIBA 3.0 and 100% of the
      Matrix reactive samples. The results showed a poor correlation among the three
      tests.

PMID- 7529245
TI  - Hepatitis C virus (HCV)-specific in vitro antibody secretion by peripheral blood
      lymphocytes: correlation with progression of disease and HCV RNA in HCV antibody
      positive patients.
AB  - Hepatitis C virus-specific in vitro antibody production (HCV IVAP) by peripheral
      blood lymphocytes in 53 HCV antibody-positive patients was investigated in
      comparison with alanine aminotransferase (ALT) levels and HCV RNA in serum
      samples. All 29 HCV IVAP-positive patients were HCV RNA positive; 26 had elevated
      ALT levels. Among the 24 HCV IVAP-negative patients, 16 were HCV RNA negative,
      with 12 presenting normal ALT values. These data indicate that HCV IVAP results
      are highly correlated (P < 0.001) with HCV RNA results and ALT levels. Our study
      indicates that HCV IVAP can be used as a novel assay in the diagnosis and
      pathogenesis exploration of HCV infection.

PMID- 7529246
TI  - Persistent and transient antibody responses to hepatitis E virus detected by
      western immunoblot using open reading frame 2 and 3 and glutathione S-transferase
      fusion proteins.
AB  - Recombinant proteins containing amino acid sequences from open reading frame
      (ORF) 2 and ORF3 of a Chinese strain of hepatitis E virus (HEV) were constructed
      as fusions with glutathione S-transferase (GST). Stable fusion proteins were
      separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the
      proteins were transferred to nitrocellulose membranes, and the immobilized
      proteins were probed with sera from hepatitis E patients from various regions or
      from rhesus monkeys (Macaca mulatta) experimentally infected with the Chinese
      strain of HEV. Immunoglobulin G-class antibodies were detected with
      chemiluminescence and anti-human immunoglobulin G conjugated to horseradish
      peroxidase. Anti-ORF3 antibodies were detected in most patients and monkeys
      within 17 days of exposure, but this humoral response declined with time and was
      usually undetectable by approximately 100 days. Anti-ORF2.1 antibody was usually
      detected as early as anti-ORF3 but persisted in all animals and many patients,
      whereas reactivity to the larger GST-ORF2.2 fusion protein was more transient,
      even though all sequences present in GST-ORF2.1 are present in GST-ORF2.2.
      Rechallenge of these monkeys with HEV suggested that immunity to reinfection was
      incomplete, as levels of anti-ORF2.1 (but not anti-ORF2.2) were boosted after
      each rechallenge. The results demonstrate that the carboxy-terminal region of HEV
      ORF2 contains epitopes which are recognized by convalescent-phase antibody and
      are likely to be associated with limited immunity to infection, but these
      epitopes may be masked when larger portions of ORF2 are expressed as recombinant
      proteins.

PMID- 7529247
TI  - Analysis of sera indeterminate by Ortho-HCV RIBA-2 by using three confirmatory
      assays for anti-hepatitis C virus antibody.
AB  - The diagnostic performances of three commercially available recombinant
      immunoblot assays (RIBAs) for anti-hepatitis C virus antibody were evaluated on
      50 ORTHO-HCV RIBA-2 (RIBA-2)-indeterminate serum samples. Concordant
      interpretations were obtained with the three tests in 60% of the samples, with
      56% positive, 2% indeterminate, and 2% negative results. Considering test
      performance in regard to the number of remaining indeterminate results, analyzing
      sera by RIBA-3, INNO-LIA HCV Ab III, and DECISCAN HCV reduced the number of
      samples reacting indeterminately to 40, 6, and 8%, respectively. The three serum
      samples classified as indeterminate in the INNO-LIA HCV Ab III as well as three
      of four serum samples interpreted as indeterminate in the DECISCAN HCV and 16 of
      20 samples classified as indeterminate in the RIBA-3 were hepatitis C virus RNA
      positive by PCR. This study clearly shows the good performance of the three tests
      as confirmatory assays compared with that of the RIBA-2. However, according to
      the manufacturers' criteria of positivity, the INNO-LIA HCV Ab III and DECISCAN
      HCV appeared to be more suitable than the RIBA-3 for interpreting serum samples
      found indeterminate in the RIBA-2.

PMID- 7529248
TI  - Differentiation of Salmonella serovar infantis isolates from human and animal
      sources by fingerprinting IS200 and 16S rrn loci.
AB  - We genotyped Salmonella serovar infantis (referred to as S. infantis), which is
      the most widespread serovar among animals and the third most common cause of
      human salmonellosis in Finland. Molecular fingerprinting of the 16S rrn locus and
      the Salmonella-specific insertion sequence IS200 was used to type the 131
      isolates originating from the main sources of S. infantis infection. The number
      of IS200 elements in S. infantis varied from zero to seven; three or more copies
      were present in 97% of the isolates, and 71% had four copies. There were four
      conserved chromosomal positions of IS200, which allowed us to group the isolates
      into three major clonal groups. We defined 11 unique IS200 profiles and five
      different ribotypes which, in combination, generated 15 genotypes highly
      restricted to the infection sources: 8 genotypes were typical of isolates from
      broiler chickens and cattle and seven genotypes were typical of isolates from
      humans. The eight genotypes of isolates from chickens represented two clonal
      groups which were differentially associated with chicken-producing companies. The
      typing scheme allows efficient discrimination between isolates from various
      infection sources and within sources and, therefore, provides a unique molecular
      tool for use in the study of the epidemiology of S. infantis infection.

PMID- 7529249
TI  - A simple, specific, and highly sensitive blocking enzyme-linked immunosorbent
      assay for detection of antibodies to bovine herpesvirus 1.
AB  - By using a monoclonal antibody directed against an epitope located on
      glycoprotein B of bovine herpesvirus 1 (BHV1), a simple, convenient blocking
      enzyme-linked immunosorbent assay (ELISA) which combines a high sensitivity with
      a low false-positive rate has been developed. The test can be performed at low
      variance on undiluted bovine serum samples. The epitope on glycoprotein B appears
      to be conserved, because it could be detected by immunostaining in all of 160
      BHV1 isolates originating from 10 countries. In testing 215 anti-BHV1 antibody
      negative and 179 anti-BHV1 antibody-positive serum samples, specificity and
      sensitivity were 0.96 and 0.99, respectively. This blocking ELISA is superior to
      a commercially available indirect ELISA and to the 24-h virus neutralization test
      in detecting low antibody levels in serum. In addition, this blocking ELISA is
      able to detect specific antibodies in serum as early as 7 days postinfection. To
      minimize any risk of introducing latent BHV1 carriers among noninfected cattle,
      this blocking ELISA would be, in our opinion, the test of choice.

PMID- 7529251
TI  - Early detection of anti-HCc antibody in acute hepatitis C virus (HCV) by western
      blot (immunoblot) using a recombinant HCV core protein fragment.
AB  - Crude extract from Escherichia coli which expressed a recombinant protein
      containing amino acids 2 to 127 of the hepatitis C virus (HCV) core protein was
      used to detect the antibody against HCV core protein (anti-HCc). After
      electrophoretic separation of proteins from the extract, Western blot
      (immunoblot) analysis was performed with the serum samples. This method was
      compared with a commercially available second-generation enzyme immunoassay (EIA)
      which employed synthetic peptides corresponding to highly antigenic segments of
      both structural and nonstructural portions of HCV. Also, reverse transcription
      PCR for HCV RNA was used for comparison. Seventy-two serum samples from three
      groups of patients were tested. Groups I and II represented healthy subjects and
      subjects with acute hepatitis A or B, respectively. Group III included patients
      with newly acquired acute hepatitis C. By Western blot analysis, 31 of 31 (100%)
      samples from group I were negative for anti-HCc antibody, whereas 4 of 22 (18%)
      samples from group II were positive for anti-HCc. One of these four samples was
      also positive for anti-HCV antibody by the second-generation EIA (1 of 22
      [4.5%]). Among 19 patients diagnosed with newly acquired acute hepatitis C, 4
      (21%) were positive for anti-HCV by the second-generation EIA, whereas 12 of 19
      (63%) were positive for anti-HCc by Western blot analysis. Of EIA-positive
      subjects, 4 of 4 (100%) were also positive for anti-HCc by Western blot analysis,
      whereas among EIA-negative subjects, 8 of 15 (53%) were positive. For HCV RNA
      detected by reverse transcription PCR, 15 of 19 (80%) of this group of samples
      were positive. Strikingly, the peak bilirubin level for patients with EIA
      negative and Western blot-positive results is significantly higher than that for
      patients with consistent EIA and Western blot results (22.7 versus 7.2 mg/dl). A
      series of serum samples from a patient with concurrent hepatitis B and C viral
      infection was also studied by both tests. Although anti-HCc persisted throughout
      the course of infection, anti-HCV by EIA converted from negative to positive 20
      days after admission and then converted back to negative 30 days later.

PMID- 7529250
TI  - Comparison of peptide enzyme-linked immunosorbent assay and
      radioimmunoprecipitation assay with in vitro-translated proteins for detection of
      serum antibodies to human papillomavirus type 16 E6 and E7 proteins.
AB  - Antibodies to human papilloma virus (HPV) type 16 (HPV-16) E6 and E7 proteins in
      serum are markers for HPV-associated invasive cervical carcinoma. We compared two
      assays, a radioimmunoprecipitation assay with in vitro-translated HPV-16 E6 and
      E7 proteins and an enzyme-linked immunosorbent assay (ELISA) with E6 and E7
      synthetic peptides, for their abilities to discriminate serologically between
      patients with invasive cervical cancer and controls. Among the patients, antibody
      prevalences were higher by the E6 radioimmunoprecipitation assay (55.7%) than by
      the E6 peptide ELISA (15.5%), but among the controls, they were lower by the
      radioimmunoprecipitation assay (1.7%) than by the E6 peptide ELISA (5%). For E7,
      antibody prevalences among the patients were comparable by the
      radioimmunoprecipitation assay (43%) and the peptide ELISA (41%), but among the
      controls they were higher by the E7 peptide ELISA (17.4%) than by the
      radioimmunoprecipitation assay (4.1%). There was good agreement between the E7
      radioimmunoprecipitation assay and the E7 peptide ELISA among patients but not
      among controls. In tests with representative sera, heat denaturation of the
      translated proteins resulted in a complete loss of reactivity to the E6 protein
      and a marked decrease in reactivity to the E7 protein. Our study showed that the
      radioimmunoprecipitation assay discriminates better than the peptide ELISA
      between patients with invasive cervical cancer and controls and that this is
      related to the ability of the radioimmunoprecipitation assay to detect
      conformational epitopes.

PMID- 7529253
TI  - Evaluation of third-generation assays for detection of anti-hepatitis C virus
      (HCV) antibodies and comparison with presence of HCV RNA in blood donors reactive
      to c100-3 antigen.
AB  - We tested serum samples from blood donors by using first-, second-, and third
      generation enzyme immunoassays or recombinant immunoblot assays. Second- and
      third-generation assays gave comparable results. Circulating hepatitis C virus
      RNA was found in a high proportion of reactive samples. A lack of reactivity or
      low-level reactivity predicted the absence of hepatitis C virus RNA in 100% of
      the cases.

PMID- 7529252
TI  - Nosocomial infection by Staphylococcus haemolyticus and typing methods for
      epidemiological study.
AB  - A patient with chronic myelogenous leukemia became colonized with a
      Staphylococcus haemolyticus strain and experienced a septic episode caused by
      this strain during a cytostatic course. The strain was multiply resistant to
      antibiotics; the MIC and MBC of vancomycin were 2 and 4 mg/liter, and the MIC and
      MBC of teicoplanin were 4 and 16 mg/liter, respectively. We performed a
      surveillance study on the carriage of S. haemolyticus in medical and nursing
      staff of the hospital ward where the patient was treated. S. haemolyticus was
      isolated from 18 sites on 12 of the 39 people tested. A number of typing methods
      were performed in order to investigate the possible relationships among the
      isolates. Methods used were immunoblotting of staphylococcal peptides, plasmid
      analysis, restriction fragment length polymorphism of chromosomal DNA, and pulsed
      field gel electrophoresis of total DNA. Compared with the immunoblotting
      technique, the molecular methods were more discriminative. The strain colonizing
      the patient showed a consistent pattern by all typing methods during isolation.
      When the immunoblot technique was used, similar patterns were found with isolates
      from hospital staff and isolates from unrelated sources. With the molecular
      techniques, no evidence of a local spread of the patient's strain was found.
      However, plasmid profiles and restriction fragment length polymorphism and pulsed
      field gel electrophoresis patterns showed that S. haemolyticus isolates collected
      from hospital ward personnel were related, which was not the case with isolates
      collected from unrelated sources. Restriction fragment length polymorphism
      analysis was more discriminative when IS431 was used as a DNA probe instead of a
      probe based on the 16S rRNA gene. S. haemolyticus, as in this case, may develop
      resistance to vancomycin and teicoplanin. These antibiotics are considered the
      last-resort drugs for the therapy of nosocomial gram-positive infections. Thus,
      local spread of staphylococci resistant to these drugs is an important problem,
      which should be prevented by strict hygienic measures and antibiotic policy.

PMID- 7529254
TI  - Simultaneous culture for adenovirus, cytomegalovirus, and herpes simplex virus in
      same shell vial by using three-color fluorescence.
AB  - A simultaneous triple culture for adenovirus, cytomegalovirus, and herpes simplex
      virus, using three different fluorochromes for virus detection and
      differentiation in the same shell vial, was developed. In evaluations the triple
      culture performed comparably to separate cultures, required less specimen volume,
      and was less expensive to perform.

PMID- 7529255
TI  - Confirmation of human Campylobacter concisus isolates misidentified as
      Campylobacter mucosalis and suggestions for improved differentiation between the
      two species.
AB  - A strain from human diarrhea originally identified as Campylobacter mucosalis
      (NCTC 12408) was examined by using 64 phenotypic characters. The similarity of
      this strain to 297 isolates of Campylobacter, Helicobacter, Arcobacter, and
      related taxa was then determined with a computer-supported data analysis program,
      MVSP. NCTC 12408 showed closest similarity to 20 type, reference, and field
      isolates of Campylobacter concisus. These strains were clearly separated from
      those of C. mucosalis in the numerical analysis of phenotypic tests; a table was
      constructed from the data used to aid in differentiating these two species in the
      clinical laboratory. The identity of NCTC 12408 was confirmed as C. concisus by
      visual comparison of its sodium dodecyl sulfate-polyacrylamide gel whole-cell
      protein electrophoregram with those of type strains of C. concisus and C.
      mucosalis. These data suggest that genuine human infection with C. mucosalis has
      not yet been reported.

PMID- 7529256
TI  - Quantitative colorimetric microneutralization assay for characterization of
      adenoviruses.
AB  - A microneutralization assay that automates the reading and interpretation of
      viral infectivity and neutralization data was developed for the characterization
      of adenoviruses (AV). Virus, serum, and cells were added to 96-well plates,
      incubated for 7 days, and stained with vital stain. The A550 of solubilized dye
      was read in a plate reader interfaced to a personal computer which analyzed the
      results. Correlation of A550 values with visual observation of cytopathic effect
      was extremely good (r = 0.977625). Clinical isolates of 17 AV from 11 patients
      were characterized by colorimetric neutralization assay. Prototype AV titers
      tested were comparable to those determined by tube methods. Prototype homotypic
      antiserum titers were comparable to or greater than those determined by standard
      tube neutralization.

PMID- 7529257
TI  - Targeted expression of transforming growth factor-beta 1 in intracardiac grafts
      promotes vascular endothelial cell DNA synthesis.
AB  - Intracardiac grafts comprised of genetically modified skeletal myoblasts were
      assessed for their ability to effect long-term delivery of recombinant
      transforming growth factor-beta (TGF-beta) to the heart. C2C12 myoblasts were
      stably transfected with a construct comprised of an inducible metallothionein
      promoter fused to a modified TGF-beta 1 cDNA. When cultured in medium
      supplemented with zinc sulfate, cells carrying this transgene constitutively
      secrete active TGF-beta 1. These genetically modified myoblasts were used to
      produce intracardiac grafts in syngeneic C3Heb/FeJ hosts. Viable grafts were
      observed as long as three months after implantation, and immunohistological
      analyses of mice maintained on water supplemented with zinc sulfate revealed the
      presence of grafted cells which stably expressed TGF-beta 1. Regions of apparent
      neovascularization, as evidenced by tritiated thymidine incorporation into
      vascular endothelial cells, were observed in the myocardium which bordered grafts
      expressing TGF-beta 1. The extent of vascular endothelial cell DNA synthesis
      could be modulated by altering dietary zinc. Similar effects on the vascular
      endothelial cells were not seen in mice with grafts comprised of nontransfected
      cells. This study indicates that genetically modified skeletal myoblast grafts
      can be used to effect the local, long-term delivery of recombinant molecules to
      the heart.

PMID- 7529258
TI  - Intravenously injected insulin-like growth factor (IGF) I/IGF binding protein-3
      complex exerts insulin-like effects in hypophysectomized, but not in normal rats.
AB  - Insulin-like growth factor (IGF) circulates in blood in two large molecular mass
      forms of 150 and 40 kD. Under normal conditions, most of the IGF is bound to the
      150-kD complex by which it is retained in the circulation and therefore unable to
      exert acute insulin-like actions. The aim of this study was to answer the
      question whether or not IGF in the 40-kD complex is bioavailable to insulin
      target tissues and thus can cause acute insulin-like effects in vivo.
      Intravenously injected 1:1 molar recombinant human (rh) IGF I/rhIGF binding
      protein (BP)-3 complex lowered blood glucose and stimulated glycogen synthesis in
      diaphragm of hypophysectomized, but not of normal rats. The serum half-lives of
      the two components of the complex were similar to each other, but considerably
      shorter in hypox than in normal rats. On neutral gel filtration of serum both
      components of the injected complex appeared predominantly in the 150-kD region in
      normal rats. In hypox rats which lack the 150-kD complex they were found in the
      40-kD region and disappeared rapidly from the circulation. We conclude that in
      the absence of the 150-kD complex, IGF associated with the 40-kD complex can
      rapidly leave the vascular compartment, reach insulin or type 1 IGF receptors and
      exert acute insulin-like effects.

PMID- 7529260
TI  - Regulation of vascular cell adhesion molecule-1 expression by IL-4 and TNF-alpha
      in cultured endothelial cells.
AB  - Interaction between vascular cell adhesion molecule-1 (VCAM-1) on endothelial
      cells and alpha 4 integrins on leukocytes is thought to mediate the selective
      recruitment of eosinophils and lymphocytes that occurs in allergic diseases. IL-4
      is associated with allergic conditions, and it has been shown to selectively
      increase expression of VCAM-1 on endothelial cells in vivo, suggesting that it
      could be responsible for VCAM-1 expression in allergic disease. Using a
      combination of immunofluorescence, flow cytometry, and Northern analysis, we
      compared the effect of TNF-alpha and IL-4 on VCAM-1 expression. TNF-alpha is also
      associated with allergic diseases, and it rapidly increases transcription of the
      VCAM-1 gene. The effect of IL-4 was relatively modest with prolonged kinetics:
      VCAM-1 was not detected until 72 h after treatment with IL-4. However, when TNF
      alpha and IL-4 were combined, there was a synergistic increase in VCAM-1
      expression and a dramatic prolongation of the appearance of VCAM-1 on the cell
      surface. This synergy results from a combination of transcriptional activation by
      TNF-alpha and the stabilization of resulting transcripts by IL-4. We propose that
      IL-4 allows subthreshold concentrations of TNF-alpha (concentrations that would
      not normally activate expression of adhesion molecules on the endothelium) to
      selectively increase VCAM-1 expression and to prolong its appearance on the
      surface of cells in allergic disease.

PMID- 7529259
TI  - Autoregulatory circuits in myeloma. Tumor cell cytotoxicity mediated by soluble
      CD16.
AB  - BACKGROUND: Multiple myeloma remains an incurable malignancy due to marked
      resistance of the tumor to standard doses of chemotherapy. Treatment approaches,
      using chemotherapeutic dose escalation and hematopoietic stem cell support have
      resulted in significant augmentation of tumor mass reduction such that complete
      remissions are effected in approximately 50% of patients. These remissions are
      however, often not durable. In the setting of minimal residual disease,
      therefore, adjunctive immunotherapy may be useful. METHODS: Peripheral blood
      mononuclear cells were studied from 28 untreated patients with multiple myeloma
      (MM). Mononuclear cell CD16 (FcR gamma III) expression was determined by flow
      cytometry. The effect of lymphocyte-derived soluble CD16, isolated by affinity
      chromatography, on MM cell growth and differentiation was assessed. MM cell
      proliferation, viability, immunoglobulin production and gene expression was
      studied. RESULTS: Data are presented indicating that cells expressing CD16 are
      increased in untreated patients with IgG-secreting myeloma. The predominant
      phenotype of these cells is CD8+ or CD56+. These CD16+ cells can produce a
      soluble form of the Fc receptor (sFcR, sCD16) that can bind to surface Ig on
      cultured human IgG-secreting myeloma cells and effect suppression of tumor cell
      growth and Ig secretion. This effector function is accompanied by concomitant
      suppression of c-myc as well as IgH and IgL gene transcription. Finally,
      prolonged exposure to sCD16 causes myeloma tumor cell cytolysis. CONCLUSIONS:
      sCD16 and possibly other soluble FcR are candidate molecules for adjunctive
      immunotherapy of myeloma, once complete responses have been effected by intensive
      cytotoxic therapy, now possible in up to 50% of newly diagnosed patients.

PMID- 7529261
TI  - Kinetics and regulation of human keratinocyte stem cell growth in short-term
      primary ex vivo culture. Cooperative growth factors from psoriatic lesional T
      lymphocytes stimulate proliferation among psoriatic uninvolved, but not normal,
      stem keratinocytes.
AB  - Flow cytometric analysis of primary ex vivo keratinocyte cultures demonstrated
      that stem cells, (beta 1 integrin+, keratin 1/keratin 10 [K1/K10-], proliferating
      cell nuclear antigen [PCNA-] [Bata-Csorgo, Zs., C. Hammerberg, J. J. Voorhees,
      and K. D. Cooper. 1993. J. Exp. Med. 178:1271-1281]) establish such cultures.
      This methodology also enabled the quantitation of synchronized recruitment of
      these cells from G0 into G1 of the cell cycle (PCNA expression), which preceded
      bright beta 1 integrin expression. (beta 1 integrinbright expression has been
      shown to be a characteristic feature of keratinocyte stem cells in culture
      (Jones, P. H., and F. M. Watt. 1993. Cell. 73:713-724). Using the above assay, we
      determined whether lesional T lymphocytes in psoriasis could be directly
      responsible for the induction of the stem cell hyperproliferation that is
      characteristic of this disease. Indeed, CD4+ T lymphocytes, cloned from lesional
      psoriatic skin and stimulated by immobilized anti-CD3 plus fibronectin, promoted
      psoriatic uninvolved keratinocyte stem cell proliferation via soluble factors.
      This induction appeared to be through accelerated recruitment of stem cells from
      their quiescent state (G0) into cell cycle. By contrast, normal keratinocyte stem
      cells exhibited no such growth stimulation. Supernatants exhibiting growth
      induction all contained high levels of GM-CSF and gamma-IFN, low IL-3 and TNF
      alpha, and variable IL-4. Only anti-gamma-IFN antibody was able to neutralize
      growth stimulatory activity of the supernatants on psoriatic uninvolved
      keratinocyte stem cells. However, because recombinant gamma-IFN alone inhibited
      growth in this assay, these data suggest that, in psoriasis, gamma-IFN acts
      cooperatively with other growth factors in the immune induction of cell cycle
      progression by the normally quiescent stem cell keratinocytes.

PMID- 7529263
TI  - Quantification of Aquaporin-CHIP water channel protein in microdissected renal
      tubules by fluorescence-based ELISA.
AB  - Several transporters have been localized along the nephron by physiological
      methods or immunocytochemistry. However, the actual abundance of these molecules
      has not been established. To accomplish this goal, we have developed a
      fluorescence-based ELISA method and have used it to quantitate Aquaporin-CHIP
      (AQP-CHIP) water channel protein in rat kidney tubules. Microdissected tubules (2
      mm/sample, permeabilized with 0.5% Triton X-100) or purified AQP-CHIP standards
      (0-200 fmol) were utilized in a fluorescence ELISA protocol after covalent
      immobilization on epoxy-activated Sepharose beads. The lower limit of detection
      was 2.4 fmol of AQP-CHIP. Preabsorption with excess purified AQP-CHIP or use of
      nonimmune serum eliminated the signal. In proximal segments, the measured AQP
      CHIP was linearly related to tubule length (1-10 mm). The measured AQP-CHIP was
      (mean +/- SE, fmol/mm): S-1 proximal, 10.8 +/- 2.1; S-2, 10.0 +/- 2.3; S-3, 21.3
      +/- 3.1; type 1 thin descending limb (DTL), 12.9 +/- 4.6; type 2 DTL, 86.5 +/-
      19.5; type 3 DTL, 43.0 +/- 11.2. In thin ascending limbs, thick ascending limbs,
      distal convoluted tubules, connecting tubules, and collecting ducts, the AQP-CHIP
      signal was indistinguishable from zero. Based on the unit water conductance of
      single CHIP molecules, our calculations show that the content of AQP-CHIP is
      sufficient to explain water permeability measured in isolated proximal tubules
      and DTL segments.

PMID- 7529262
TI  - Role of nitric oxide in parasympathetic modulation of beta-adrenergic myocardial
      contractility in normal dogs.
AB  - In vitro studies indicate that muscarinic cholinergic inhibition of beta
      adrenergic cardiac responses may be modulated in part by nitric oxide (NO). To
      evaluate the role of NO in parasympathetic inhibition of the beta-adrenergic
      contractile response in vivo, we assessed the inotropic response to dobutamine
      before and during bilateral vagus nerve stimulation in closed-chest dogs.
      Dobutamine administration and vagal stimulation were repeated during
      intracoronary infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L
      NMMA, 10 mumol/min) and again following infusion of L-arginine (100 mg/kg). In
      eight dogs, intracoronary dobutamine infusion at rates of 25 and 50
      micrograms/min increased peak +dP/dt by 131 +/- 24 and 168 +/- 22%, respectively
      (P < 0.0001). Vagal stimulation (2.5 Hz) attenuated the responses to dobutamine
      (25 and 50 micrograms/min) by 23 +/- 4 and 21 +/- 4%, respectively (P < 0.001). L
      NMMA reduced (by 44-62%; P < 0.001) and L-arginine restored vagal inhibition of
      the dobutamine-stimulated inotropic response. In a second group of nine dogs,
      dobutamine was administered systemically to assure a constant concentration in
      the coronary circulation. Vagal stimulation (2.5 Hz) attenuated the dobutamine
      stimulated inotropic response (2.5 and 5.0 micrograms/kg per min) by 40 +/- 12%
      and 57 +/- 8%, respectively (P < 0.004). As with intracoronary dobutamine, L-NMMA
      diminished and L-arginine restored vagal inhibition of the inotropic response to
      dobutamine. Intracoronary infusion of atropine (12 micrograms/min) abolished the
      vagal inhibitory effect, and intracoronary infusion of 8-bromo-cyclic GMP (1 and
      10 mM) caused a dose-dependent attenuation of the dobutamine-stimulated increase
      in +dP/dt. These data suggest that NO mediates, at least in part, vagal
      inhibition of the inotropic response to beta-adrenergic stimulation by
      dobutamine, and thus may play a role in normal physiologic regulation of
      myocardial autonomic responses.

PMID- 7529266
TI  - Functional anatomy of the thalamus in the blind mole rat Spalax ehrenbergi: an
      architectonic and electrophysiologically controlled tracing study.
AB  - The occipital cortex of the naturally blind mole rat, Spalax ehrenbergi, is
      occupied by an area of somatosensory representation. To date, no visual cortex
      has been identified electrophysiologically. In order to determine whether there
      are corresponding modifications in the thalamus, thalamocortical connections were
      studied with neuroanatomical tracing methods. Three different fluorescent tracers
      were injected under electrophysiological control into distinct cortical areas.
      Injections into the somatosensory head/face and hindlimb/trunk areas of
      representation revealed a posteromedial ventral nucleus and a posterolateral
      ventral nucleus, respectively. Additional somatotopic labeling was found in an
      area dorsomedial to the two ventral nuclei. This structure may be equivalent to
      the posterior nuclear complex in the laboratory rat. Injections into the auditory
      cortex of the mole rat resulted in labeling of the medial geniculate body. In
      contrast to the situation in the laboratory rat, in which a prominent
      dorsolateral geniculate body and a ventrolateral geniculate body assume
      dorsolateral positions, the somatosensory thalamus of the mole rat almost reaches
      the dorsolateral surface. This finding is corroborated by the results of the
      architectonic study, which failed to reveal a differentiated lateral geniculate
      body. Our observations suggest that the thalamocortical visual system in the mole
      rat is minute, whereas the somatosensory system is expanded. This situation fits
      the mode of life of this subterranean animal, for which touch is more important
      than vision.

PMID- 7529267
TI  - Nitric oxide synthase in the brain of the turtle Pseudemys scripta elegans.
AB  - The distribution pattern of nitric oxide synthase (NOS) was investigated in the
      brain of the turtle by NADPH-diaphorase histochemistry. The specificity of the
      histochemical staining was tested by immunocytochemical colocalization with an
      antiserum specific for NOS. In the forebrain, neurons staining intensely for
      nitric oxide synthase were localized in the olfactory tubercle, the basal ganglia
      complex, the basal amygdaloid nucleus, suprapeduncular nucleus, and the posterior
      hypothalamic area. Many positive fibers course in a tract connecting the basal
      amygdaloid nucleus with the hypothalamus, corresponding to the stria terminalis.
      Bundles of nitroxergic fibers were seen to course at the ventromedial edge of the
      optic tract and to cross in the supraoptic decussation, apparently consisting of
      tectothalamic and thalamotectal fibers. In the midbrain, strongly NOS-positive
      neurons were present in the substantia nigra, the nucleus profundus mesencephali,
      the periventricular grey of the optic tectum, the laminar nucleus of the torus
      semicircularis, and the nucleus of the lateral lemniscus. The area of the locus
      coeruleus harbored an accumulation of intensely stained neurons, which, as in
      mammals, might represent a cholinergic cell group of the reptilian brainstem. In
      the cerebellum, strong staining was confined to bundles of afferent fibers
      running in the lower molecular and in the Purkinje cell layer. These axons
      appeared to include ascending projections from the dorsal funicular nucleus or
      the spinal cord. NOS-positive cells in the caudal brainstem were found in the
      cerebellar nuclei, in the superior vestibular nucleus, in the reticular nuclei,
      ventrolateral to the nucleus of the solitary tract, in the perihypoglossal, and
      in the dorsal funicular nucleus. Taken together, these results suggest that
      nitric oxide acts as a messenger molecule in different areas of the reptilian
      brain and spinal cord. In certain areas, the pattern of expression of NOS appears
      to have evolved before radiation of present mammalian, avian, and reptilian
      species.

PMID- 7529265
TI  - Two major types of premotoneurons in the feline trigeminal nucleus oralis as
      demonstrated by intracellular staining with horseradish peroxidase.
AB  - Previous studies suggest that neurons in the dorsomedial subdivisions of
      trigeminal nucleus oralis (Vo) may contribute to reflex control of jaw movements
      and to modulation of sensory information. The present study has addressed this
      possibility by the use of intracellular staining with horseradish peroxidase of
      physiologically identified neurons in Vo to examine functional and morphological
      properties of these neurons. Of 14 labeled neurons, eight had axon collaterals
      terminating exclusively in the dorsolateral subdivision of the trigeminal motor
      nucleus (DL neurons) and four in its ventromedial subdivision (VM neurons); axon
      collaterals of two neurons were not traced. Both groups of neurons sent terminal
      arbors into other nuclei of the lower brainstem. The DL neurons were
      distinguishable from the VM neurons in their receptive field (RF) location,
      neuronal position, somadendritic architecture, and projections to other brainstem
      nuclei. All neurons, except for two that were exclusively activated by noxious
      stimuli applied to the tongue, were responsive to light mechanical stimulation of
      peri- and intraoral structures. The RFs of the DL neurons were located in more
      posterior oral structures than those of the VM neurons. The RF of nearly all low
      threshold DL neurons was located in the maxillary region, and that of the VM
      neurons, in contrast, involved the mandibular region. The VM neurons were located
      medial or ventral to the DL neurons. The soma size of the VM neurons was
      significantly larger than that of the DL neurons. Dendritic arbors of both groups
      could be separated into medial and lateral components. The ratio of the dendritic
      transverse areas in the medial vs. lateral component was significantly higher in
      the VM neurons than in the DL neurons. The DL neurons also issued collaterals
      that terminated in larger brainstem areas than those of the VM neurons. These
      observations provide new evidence on the morphological and functional properties
      of Vo neurons that contribute to reflex control of jaw and facial movements and
      modulation of sensory information.

PMID- 7529264
TI  - Normal activity-dependent refinement in a compressed retinotectal projection in
      goldfish.
AB  - When the optic nerve in a goldfish is crushed, regenerating fibers can reform a
      normal retinotopic projection. Two processes are thought to generate this
      retinotopic order. One is an activity-independent process, presumed to be some
      form of substrate-directed growth, which generates rough retinotopy as seen in
      the early formed projection. The other is an activity-dependent process that
      generates fine retinotopy during a protracted period of refinement. This
      projection also displays two other behaviors. One is retinotopic plasticity, in
      which optic fibers can compensate for retinal or tectal ablations by expanding or
      compressing into the available tectal space while preserving retinotopic order.
      These plasticities can dramatically alter the scale of the projection. The other
      behavior is the formation of fixed synaptic sites in tectum. Optic fibers make a
      characteristic number of synaptic connections in tectum, which is not changed by
      increasing the number of invading optic fibers. This has been interpreted to mean
      that fibers compete for limited synaptic sites. How the two processes that
      generate order, substrate-directed growth, and activity-dependent refinement
      might each be affected by the expression of retinotopic plasticity and altered
      synaptic competition is largely unknown. In particular, it is not known how fine
      retinotopic order (activity-dependent refinement) might be affected by altering
      the scale of the projection. Would optic fibers from neighboring ganglion cells
      converge into the same-sized area of tectum, or would they expand or compress in
      proportion to the altered scale of the overall map? To explore this issue, the
      posterior half of tectum of goldfish was removed, and the optic nerve was
      crushed, thereby forcing regenerating fibers to form a compressed retinotopic
      projection onto the anterior half of tectum. Under these conditions, optic fibers
      are also forced to compete for half the normal number of synaptic sites. The
      effect on retinotopy was monitored at various times during regeneration by making
      a small spot injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP)
      into nasal retina corresponding to fibers that would normally terminate in the
      missing posterior half of tectum. To distinguish between activity-dependent and
      activity-independent processes, retinal impulse activity was blocked in some
      animals by repeated intraocular injections of tetrodotoxin. The initial
      projection was found to be unaffected by impulse activity. Regardless of
      activity, nasal fibers failed initially to grow to the most posterior available
      regions, but instead were dispersed across much of the "incorrect" anterior half
      of tectum at 30 days.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7529268
TI  - Galanin immunoreactivity in autonomic innervation of the cat eye.
AB  - In an immunohistochemical study, we find that galanin is much more widely
      distributed in the peripheral innervation of the cat eye than in other animals so
      far examined. Previous studies of rat and pig eyes have revealed sparse galanin
      positive nerves that presumably originate in the trigeminal ganglion. In
      contrast, the cat has a rich supply of galanin-containing nerve fibers throughout
      the uvea. Galanin-positive varicose nerves concentrate densely in iris muscles
      and distribute more sparsely in the ciliary muscle. The ciliary processes have a
      plexus of galanin-positive nerves underlying the ciliary epithelium at their base
      and positive nerve fibers coursing within their stroma. The ciliary artery and
      its branch vessels in the uvea are invested with a dense plexus of galanin
      positive nerves. All autonomic ganglia supplying the eye contain cells that
      express galanin. It is present in 97% of superior cervical ganglion cells,
      coexisting with both tyrosine hydroxylase and neuropeptide Y; in 80% of
      pterygopalatine ganglion cells, most of which also contain vasoactive intestinal
      peptide; and in approximately 25% of ciliary ganglion cells. After unilateral
      superior cervical ganglionectomy, galanin-positive nerves almost totally
      disappear from the iris muscles, demonstrating that they are predominantly of
      sympathetic origin. Galanin-positive nerves investing the ciliary artery and
      choroidal blood vessels are not detectably reduced by sympathectomy, indicating
      that perivascular parasympathetic nerves from the pterygopalatine ganglion also
      express galanin. Other galanin-containing nerves in the eye can originate from
      the trigeminal and ciliary ganglia. The prominence of galanin in the ocular
      autonomic innervation of the cat provides an opportunity to explore the
      physiological effects of this neuropeptide in the eye.

PMID- 7529269
TI  - Creating a new learning experience: "The story of art" and "Prudent art".
AB  - The signs and symptoms of an impending cardiac arrest and the appropriate
      interventions are two concepts that need to be taught in the American Heart
      Association's Basic Life Support (BLS) course. CPR education is also required
      annually for all hospital employees who are direct caregivers. Developing
      teaching strategies that renew interest in the content and facilitate learning
      and retention is a challenge for BLS instructors. "The Story of Art" and "Prudent
      Art" utilize narrative and visual images to teach the signs and symptoms of an
      impending cardiac arrest and appropriate interventions. This article describes
      the development of this creative learning experience.

PMID- 7529270
TI  - Effect of aibellin, a peptide antibiotic, on propionate production in the rumen
      of goats.
AB  - Aibellin was administered in feed to goats (16 to 18 kg of BW) for 12 d. At 80
      mg/d, the molar percentage of propionate in rumen fluid increased significantly
      in 8 d, and the effect lasted for as long as 10 d after administration ceased.
      Total VFA concentration, protozoa numbers, and NDF digestibility were not
      depressed significantly at this dosage but were reduced at 100 mg/d with little
      further increase in the molar percentage of propionate. Therefore, the optimal
      dosage of aibellin was 80 mg/d under our experimental conditions. In contrast,
      monensin (30 mg/d) and gramicidin D (60 mg/d) decreased total VFA concentration
      and protozoa numbers when supplemented to obtain molar percentages of propionate
      comparable to 80 mg/d of aibellin. From these results, aibellin may be easier and
      safer to use than monensin and gramicidin D to modify rumen fermentation.

PMID- 7529272
TI  - Severe neurological complications following orthotopic liver transplantation in
      patients receiving FK 506 and prednisone.
AB  - The objective of this study was to define the severe neurological complications
      that occur in recipients of an orthotopic liver transplantation, receiving FK 506
      as their primary immunosuppressive agent. To accomplish this, 100 consecutive
      orthotopic liver transplantation patients were followed prospectively from the
      time of their transplant until the date of their initial post-orthotopic liver
      transplantation discharge from hospital. All major neurological complications
      occurring during this period were recorded and assessed. The frequency of severe
      neurological complications occurring in these severely ill transplant recipients
      was 34%. Delirium was noted in 16, coma in 9, seizures in 4, and 5 developed
      focal motor deficits associated with the finding of a brain abscess, transient
      ischemic attack or central pontine myelinolysis. At the time at which a major
      neurologic complication was noted, the blood level of FK 506 was recorded. No
      direct relationship between FK 506 blood levels and the presence or absence of
      major neurologic complications of orthotopic liver transplantation could be
      demonstrated. Based upon this series, it can be concluded that although FK 506
      may contribute to the pathogenesis of minor neurological complications seen after
      orthotopic liver transplantation such as tremors and headaches, the pathogenesis
      of most of the major neurologic complications occurring after orthotopic liver
      transplantation is multifactorial and cannot be ascribed solely to FK 506
      toxicity.

PMID- 7529271
TI  - Hepatitis C virus antibody and hepatitis C virus replication in chronic hepatitis
      B patients.
AB  - We assessed hepatitis C virus infection in 156 chronic hepatitis B patients using
      second-generation hepatitis C virus antibody (anti-HCV). Active virus replication
      was further investigated in anti-HCV-positive cases by means of polymerase chain
      reaction assay for the detection of serum hepatitis C virus RNA. Anti-HCV
      prevalence was higher in patients negative for hepatitis B e antigen (HBeAg)
      (10/48, 21%) than in HBeAg-positive patients (10/108, 9%) (p < 0.05), and the
      reactivity (cut-off index) in anti-HCV enzyme-linked immunosorbent assay of the
      positive cases was significantly higher in HBeAg-negative patients (4.1 +/- 0.1)
      than in -positive ones (3.6 +/- 0.6) (p < 0.05). The prevalence of hepatitis C
      virus RNA in anti-HCV-positive cases was also higher in the HBeAg-negative group
      (9/10, 90%) than in the -positive group (3/10, 30%) (p < 0.01). Viremia was found
      in association with high reactivity in anti-HCV ELISA (cut-off index > 3.5) in
      both groups. Nine (90%) of 10 such cases were viremic in the HBeAg-negative group
      compared with three (43%) of seven in the HBeAg-positive group (p < 0.05). These
      results suggest that hepatitis C virus replication may be influenced by hepatitis
      B virus replicative states, indicating possible interference between hepatitis B
      and C viruses.

PMID- 7529273
TI  - Etiology of chronic hepatitis in France: predominant role of hepatitis C virus.
AB  - The aim of this study was to assess the causes of histologically proven chronic
      hepatitis in a series of 357 consecutively admitted patients. Patients with
      chronic alcohol intake above 50 g per day, Wilson's disease, idiopathic
      hemochromatosis or homozygous alpha-1 antitrypsin deficiency were excluded. Sera
      of all patients were tested for antibodies to hepatitis C virus with second
      generation enzyme-linked immunoassay and recombinant immunoblot assay, for
      markers of hepatitis B and hepatitis D viruses, and for autoantibodies. Detection
      of hepatitis C viral RNA by polymerase chain reaction was attempted if
      recombinant immunoblot assay was indeterminate, or if both viral and autoimmune
      markers were absent. If no serum markers, including HCV RNA, were found, the
      cause of chronic hepatitis was considered as unknown. The cause of chronic
      hepatitis was found in 343 cases (96.4%), including three patients with HCV RNA
      as the only marker. Chronic hepatitis was related to hepatitis C virus in 51.8%,
      to hepatitis B virus in 32.8% (including hepatitis D infection in 3.1%), and to
      autoimmune hepatitis in 5.9% of cases, respectively. No case of drug-induced
      chronic hepatitis was observed in this series, and in 5.9% of cases, there were
      probably multiple causes. Finally, in 3.6% of the cases the cause of chronic
      hepatitis remained unknown despite extensive evaluation suggesting the existence
      of a non-A, non-B, non-C viral agent.

PMID- 7529274
TI  - Hepatitis C virus RNA and antibodies among blood donors in Beijing.
AB  - Blood units from voluntary as well as commercial donors in Beijing, China, were
      tested for hepatitis C virus RNA and antibodies, and for serological markers of
      hepatitis B virus infection. HCV RNA was detected less frequently in 1909
      voluntary donors (5 (0.3%)), than in 1017 commercial donors (58 (5.7%)) (p <
      0.001). Antibody to hepatitis C virus was detected by the second-generation
      enzyme immunoassay in 55 (87%) of 63 blood units with viremia. Evidence of
      present or past infection with hepatitis B virus was common both in voluntary
      (43.9%) and commercial (46.4%) donors. There were eight (13%) sera with HCV-RNA
      in which hepatitis C virus antibodies were not detectable by second-generation
      enzyme immunoassay. Of 63 HCV-RNA samples from donors, 33 (52%) were of genotype
      II, 18 (29%) of III and one (2%) of II + III. HCV-RNA in the remaining 11 (17%)
      were not classifiable into any of the genotypes I, II, III, IV and V. Genotype II
      was more frequent in viremic donors with elevated alanine aminotransferase levels
      (13/18 or 72%) than in those with normal levels (20/45 or 44%). These results
      indicate a low prevalence of hepatitis C virus infection in the general
      population in Beijing, and the limitations of identifying sera with viremia by
      second-generation enzyme immunoassay.

PMID- 7529275
TI  - Cross-reactivity of anti-Mycobacterium gordonae antibodies with the major
      mitochondrial autoantigens in primary biliary cirrhosis.
AB  - Primary biliary cirrhosis is a chronic cholestatic liver disease associated with
      autoimmune disorders. Antimitochondrial autoantibodies and granulomatous portal
      lesions are characteristic in primary biliary cirrhosis. Since granuloma may be
      induced by Mycobacteria, and there is evidence implicating Mycobacteria as
      infectious agents capable of initiating autoimmunity, a study was performed to
      determine the presence of antibodies against 10 atypical Mycobacteria in 19
      patients with primary biliary cirrhosis, and in 35 controls (25 patients with
      other chronic liver diseases and 10 healthy subjects). All primary biliary
      cirrhosis sera and none of the controls reacted with the extract from
      Mycobacterium gordonae, showing identical recognition profiles with two
      polypeptides of 70-65 and 55 kDa. No other reaction was found in primary biliary
      cirrhosis patients and in controls with the extracts from the other nine atypical
      Mycobacteria tested. Eluted immunoglobulins which reacted with the 70-65 and 55
      kDa polypeptides from M. gordonae, bound to the mitochondrial antigens PDH-E2 and
      BCKDH-E2. Furthermore, when the extract from M. gordonae was tested with eluted
      immunoglobulins from recognized PDH-E2 and BCKDH-E2 by primary biliary cirrhosis
      patients, we observed both 70-65 and 55 kDa polypeptides. These data indicate
      that antibodies to M. gordonae, found in all primary biliary cirrhosis patients,
      cross-react with the major mitochondrial targets of the disease. We suggest that
      M. gordonae may play a potential pathogenic role in primary biliary cirrhosis.

PMID- 7529276
TI  - Pressure control of renal renin release in Lyon hypertensive rats.
AB  - OBJECTIVE: To assess whether the pressure-independence of renin release by
      isolated kidneys of Lyon hypertensive (LH) rats could result from long-term
      exposure to high blood pressure, sodium retention or an altered regulation of
      intracellular calcium through L-type voltage operated channels. DESIGN: Renin
      release was studied in kidneys from LH rats, either controls or chronically (aged
      3-7 weeks) treated with hydralazine or deprived of sodium. The influence of L
      type calcium channels was studied acutely using a specific activator (BAY K8644)
      or modulator (verapamil). Lyon low blood pressure (LL) rats served as controls.
      METHODS: Kidneys were isolated from LH or LL rats aged 7 weeks and single-pass
      perfused at three pressure levels: 70, 85 and 160 mmHg. RESULTS: LH rat kidneys
      differed from LL rat kidneys in having elevated vascular resistances, decreased
      glomerular filtration rate, pressure natriuresis and pressure-dependent renin
      release. Hydralazine treatment and sodium deprivation did not significantly
      modify the pressure-independence of renin release by LH rat kidneys. BAY K8644 (1
      x 10(-8) and 5 x 10(-8) mol/l) induced significantly greater vasoconstrictor
      effects in LH than in LL rat kidneys but did not affect the renin release already
      stimulated by low perfusion pressure. Verapamil (5 x 10(-6) mol/l) dilated LH
      more than LL rat kidneys. It did not change the renin release observed at low,
      but enhanced it at high, perfusion pressure. This effect was more marked in LL
      than in LH rat kidneys. CONCLUSIONS: The poor stimulation of renin release by low
      perfusion pressure in LH rat kidneys does not appear to be a consequence of high
      blood pressure level, sodium retention and alteration in L-type calcium channels.
      However, results demonstrate that these channels participate in the increased
      vascular resistances exhibited by LH rat kidneys.

PMID- 7529277
TI  - Increased levels of the soluble adhesion molecule E-selectin in essential
      hypertension.
AB  - OBJECTIVE: To determine whether soluble E-selectin levels were raised in
      hypertension and whether such levels correlated with those of von Willebrand
      factor. DESIGN: Forty-five consecutive patients with uncontrolled hypertension
      (blood pressure > 140/90 mmHg) and 33 consecutive patients with controlled
      hypertension (blood pressure < 140/90 mmHg, i.e. normotension) were examined and
      compared with 40 normotensive age- and sex-matched controls. METHODS: Levels of
      von Willebrand factor and soluble E-selectin were measured by enzyme-linked
      immunosorbent assay in venous blood serum. Resting systolic (SBP) and diastolic
      (DBP) blood pressures were measured before venepuncture. RESULTS: Soluble E
      selectin levels were raised in hypertension compared with controls and
      normotension. The levels of von Willebrand factor were raised in hypertension and
      normotension compared with controls. In multivariate analysis of all subjects,
      von Willebrand factor levels correlated with SBP (P < 0.001) and soluble E
      selectin level correlated with DBP (P < 0.001), but levels of von Willebrand
      factor and soluble E-selectin did not correlate. There was no clear relationship
      between levels of either endothelial cell index or the class of drug therapy used
      or its dosage. CONCLUSIONS: We suggest that raised levels of soluble E-selectin
      in hypertension do not indicate endothelial cell injury but may be related to
      endothelial cell activation. The stimulus for release of soluble E-selectin might
      be different from that for von Willebrand factor.

PMID- 7529278
TI  - Dendritic cells are the most efficient in presenting endogenous naturally
      processed self-epitopes to class II-restricted T cells.
AB  - Dendritic cells (DC) are potent APCs, able to induce efficiently primary T cell
      mediated responses to foreign Ags. To assess the efficiency of DC, as compared
      with other APC types, in the in vivo presentation of self-Ags to CD4+ T cells, we
      analyzed processing and presentation to class II-restricted T cells of endogenous
      naturally processed self-epitopes constitutively expressed by mouse APC. Mouse
      beta 2-microglobulin (m beta 2-m) peptides corresponding to residues 26-39 and 24
      36 are constitutively presented, in mice expressing m beta 2-m, by I-Ad and I-Ed
      molecules respectively, as demonstrated by activation of m beta 2-m-specific T
      cell hybridomas generated in BALB/c beta 2-m-deficient mice. These dominant,
      naturally processed self-epitopes of m beta 2-m are presented by APC from a
      variety of tissues, including the thymus. To analyze the relative efficiency of
      different APC populations in the presentation of self-beta 2-m, the ability of
      purified DC, macrophages, and large or small B cells to stimulate m beta 2-m
      specific T cell hybridomas was tested. Naturally processed self-m beta 2-m
      epitopes are constitutively presented to T cells by any class II-positive APC
      tested, but with highest efficiency by splenic and thymic DC, followed by
      macrophages, large B cells, and small B cells. This hierarchy of self-beta 2-m
      presentation does not depend on differential processing capacity of these APC
      populations, and it correlates with expression of CTLA-4 ligands and ICAM-1
      molecules, rather than with expression of class II molecules.

PMID- 7529280
TI  - Fas antigen-mediated DNA fragmentation and apoptotic morphologic changes are
      regulated by elevated cytosolic Ca2+ level.
AB  - More than 80% of cells of the human B cell line FMO, which expresses the Fas Ag,
      underwent apoptosis within 2 h after addition of an anti-Fas mAb. Rises in
      cytosolic Ca2+ concentration ([Ca2+]i) and their effects were investigated by
      imaging individual cells continuously and introducing Ca2+ chelators to the
      outside and/or inside of the cell. The typical Ca2+ response consisted of 1) an
      early [Ca2+]i rise (basal [Ca2+]i, 85 to 110 nM; peak, 140 to 200 nM; duration,
      15 to 20 min), 2) sustained elevation of [Ca2+]i at 140 to 150 nM, 3) a second
      Ca2+ rise (200 to 500 nM, 15 to 30 min) between 1.5 and 2 h, and 4) a large
      [Ca2+]i rise (1.2 to 2.0 microM) between 2 and 4 h after addition of mAb.
      Responses 1, 3, and 4 were mainly caused by Ca2+ entry, and response 2 involved
      intracellular Ca2+ release from stores. Apoptosis could be induced by mAb even in
      Ca(2+)-deprived external medium. Chelating cytosolic Ca2+ revealed that the
      [Ca2+]i rise is a prerequisite for fragmentation of DNA and chromatin, and is
      also necessary for fragmentation of cells. The critical [Ca2+]i was 140 to 150 nM
      and a sustained [Ca2+]i rise was more effective. A [Ca2+]i rise itself (without
      mAb) was ineffective. About 20% of mAb-treated cells showed chromatin
      condensation at the periphery of the nucleus (possibly an earlier stage of
      nuclear change) and a bubble-like cell shape even when [Ca2+]i was held below 100
      nM. Thus, Ca2+ is mobilized immediately after Fas stimulation and functions as a
      key factor causing advanced apoptotic changes. Response 4 was related to
      secondary necrosis.

PMID- 7529279
TI  - Limited restriction in the TCR-alpha beta V region usage of antigen-specific
      clones. Recognition of myelin basic protein (amino acids 84-102) and
      Mycobacterium bovis 65-kDa heat shock protein (amino acids 3-13) by T cell clones
      established from peripheral blood mononuclear cells of monozygotic twins and HLA
      identical individuals.
AB  - We have analyzed the TCR-alpha beta repertoire specific for a given peptide/MHC
      complex by using pairs of HLA-identical individuals ranging from monozygotic
      twins to unrelated individuals to examine the contribution of genetic background
      and HLA expression in shaping the potential response to a single antigenic
      epitope. This panel has been previously defined, demonstrating that the
      concordance of the peripheral TCR-alpha beta repertoires directly correlates to
      the level of relation and HLA identity. We have analyzed peptide-specific T cell
      clones derived from T cell lines from these individuals specific for MHC class II
      restricted peptides: Mycobacterium bovis 65-kDa heat shock protein (65-kDa hsp)
      amino acids (aa) 3-13 (DR3-restricted), and myelin basic protein aa 84-102 (DR2
      restricted). DNA sequence analysis was used to determine the composition of the
      TCR-alpha beta V regions. Although the overall TCR-alpha beta repertoires between
      individuals were diverse, an intra-individual limited restriction was evident.
      There was also a limited conservation in the response to the different peptides:
      high frequencies of V beta 2, 4, 7, 19, V alpha 21, and J alpha 17 responded to
      the MBP aa84-102, whereas these V/J regions were limited or absent in the 65-kDa
      hsp aa3-13 repertoire. Similarly, V beta 5.1 and J alpha 9 were increased in the
      65-kDa hsp aa3-13 repertoire. Within the CDR3s, motifs could be identified that
      were similar between twins. Furthermore, one of these motifs resembled CDR3s
      previously found in corresponding animal models. Similarities could also be seen
      in the CDR3s of T cell clones sharing V gene usage and peptide specificity. Thus,
      the in vitro response to antigenic peptides seems to be quite heterogeneous
      overall and individual specific.

PMID- 7529281
TI  - In vivo state of antiviral CTL precursors. Characterization of a cycling cell
      population containing CTL precursors in immune mice.
AB  - The in vivo state of CD8+ mouse memory CTL specific to lymphocytic
      choriomeningitis virus (LCMV) was characterized. During acute LCMV infection, the
      majority of the LCMV-specific CTL activity tested immediately ex vivo was
      mediated by CD8+ L-selectin- Mac-1+ CTL. The L-selectin- population of CD8+ cells
      elicited during acute infection also carried > 99% of the restimulatable CD8+ CTL
      precursors (CTLp) to LCMV, and these required added IL-2 for development into
      effectors in vitro. In contrast with the acute infection, most of the virus
      specific CTLp in immune mice were L-selectin+. Examination of CD8+ T cells in
      LCMV-immune mice revealed that a L-selectin+ blast-size population of cycling
      CD8+ cells contained CTLp, which developed into effector CTL in the absence of
      added IL-2. These cells also expressed Mac-1 and IL-2R. Flow cytometric sorting
      for IL-2R+ and IL-2R- CD8+ cells in the immune animal revealed, by limiting
      dilution analysis, similar frequencies of CTLp in both populations. In bulk
      restimulation assays, the CD25+ CTLp did not require added IL-2 for their in
      vitro development into effectors, whereas the CD25- CTLp did. Hence, the
      different requirements for CTLp to effector development in vitro reflect
      qualitative differences in the in vivo state of the CTLp in the various
      subpopulations. LCMV-specific memory CTLp that did not require added IL-2 for
      differentiation were also found in the small-size, noncycling, CD8+L-selectin-
      cells. In contrast, the small-size, noncycling, CD8+L-selectin+, and CD8+IL-2R-
      populations also carried CTLp, but these required added IL-2 for development into
      effector CTL. Hence, T cell memory to LCMV is distributed among various
      lymphocyte subpopulations in immune animals, and the presence of an activated
      cycling cell component may account for the long-term perpetuation of antiviral
      immunologic memory.

PMID- 7529283
TI  - Binding of a peptide antigen to multiple HLA alleles allows definition of an A2
      like supertype.
AB  - Direct MHC binding assays with radiolabeled peptides and HLA class I-expressing
      mammalian cells such as EBV-transformed B cell lines and PHA-activated blasts
      have been developed. Significant binding of the radiolabeled probe could be
      obtained if the target cells were preincubated overnight at 26 degrees C in the
      presence of beta 2-microglobulin. Under these conditions, up to a few percent of
      the HLA molecules expressed by either cell type could be bound by the labeled
      peptides. With these assays, the degree of cross-reactivity of the A*0201
      restricted hepatitis B virus core 18-27 peptide with other A2 subtypes was
      examined. It was determined that this peptide epitope also binds the A*0202,
      A*0205, and A*0206 but not A*0207 subtypes. Inhibition experiments with panels of
      synthetic peptide analogues underlined the similar ligand specificities of the
      HLA-A*0201, A*0202, and A*0205 alleles. Analysis of the polymorphic residues that
      help form the B and F pockets of various HLA alleles allowed prediction of
      binding of the hepatitis B virus core 18-27 epitope to two other HLA alleles (HLA
      A*6802 and A*6901). Thus, it appears that a family of at least six different HLA
      A molecules may share overlapping ligand specificities (aliphatic residues in
      position 2 and at the C termini). These results suggest that broadly cross
      reactive peptide epitopes can be identified and greatly enhance the prospective
      feasibility of peptide-based vaccination approaches.

PMID- 7529284
TI  - HLA-A*0201 complexes with two 10-Mer peptides differing at the P2 anchor residue
      have distinct refolding kinetics.
AB  - The immune response to viruses partially depends on the biochemical interaction
      between viral peptides and histocompatibility molecules. In this study, the
      refolding of recombinant HLA-A*0201 heavy chain and beta 2-microglobulin (beta 2
      m) in the presence of peptides from influenza B nucleoprotein (BNP), influenza A
      matrix protein, and HIV gp120 and their analogues was examined. The plateau value
      for the amount of refolded complex with three peptides, a 10-mer BNP 85-94 (A86)
      with alanine substituted for leucine at the P2 anchor residue and two BNP 8-mers,
      was significantly lower than the native peptide epitope BNP 85-94 or with other
      peptides tested. To attempt to understand the basis for the lower yield of
      complex, equilibrium dissociation constants (KdS) for the two 10-mers, BNP 85-94
      (A86) and BNP 85-94, were determined from association and dissociation rates and
      from Scatchard plots, all measured at 10 degrees C. In addition, dissociation
      rates were measured at 0 degrees, 26 degrees, and 37 degrees C. Although the
      kinetics were similar at 0 degrees and 10 degrees, at 37 degrees these two
      complexes had distinct rates of dissociation, resulting in relatively stable or
      unstable complexes. The behavior of the unstable complexes paralleled the
      behavior of empty complexes described in vivo; they are unstable at physiologic
      temperature, produced in low yield, and stabilized by low temperature. Comparison
      of all of the kinetic data suggests that the equilibrium amounts of the two
      HLA/peptide complexes (plateau values) result from distinct reaction pathways,
      i.e., that the molecules that form stable complexes may undergo an additional
      reaction to those that form unstable complexes.

PMID- 7529285
TI  - The WI-1 antigen of Blastomyces dermatitidis yeasts mediates binding to human
      macrophage CD11b/CD18 (CR3) and CD14.
AB  - Three genetically related strains of Blastomyces dermatitidis (Bd) yeasts that
      differ in their expression of WI-1, an immunodominant cell wall Ag, were tested
      for their capacity to bind to human macrophages (M phi) in the absence of serum.
      These strains included American Type Culture Collection (ATCC, Rockville, MD)
      ATCC 26199, which is virulent for mice; an attenuated mutant strain ATCC 60915,
      which expresses 2.5-fold more WI-1 than strain 26199; and an avirulent mutant
      strain, ATCC 60916, which has sixfold more WI-1 than strain 26199. Attachment of
      both mutant strains to M phi was rapid and was maximum after 10 min at 37 degrees
      C. Attachment of strain 26199 to M phi was approximately 40% of that obtained
      with the mutants. Binding of Bd to M phi was temperature- and Mg(2+)-dependent,
      and heat-killed yeasts bound to M phi as well as viable yeasts. Experiments with
      receptor-specific mAbs demonstrated that 26199 yeasts bound predominantly to the
      LPS binding site on CD11b/CD18 (CR3). However, the mutants bound to M phi CD14 as
      well as CR3. Fab anti-WI-1 inhibited the binding of all strains to M phi by 69 to
      78%. Latex microspheres coated with purified WI-1 or a 25-amino acid tandem
      repeat located within WI-1 also bound to M phi CR3 and CD14. These data
      demonstrate that: 1) WI-1 is a major ligand on Bd that mediates attachment of
      yeasts to human M phi; 2) the binding activity of WI-1 is located within the 25
      amino acid tandem repeat; and 3) binding of Bd yeasts to M phi is mediated
      through the LPS binding site on CR3 and CD14.

PMID- 7529282
TI  - Definition of a lamina propria T cell responsive state. Enhanced cytokine
      responsiveness of T cells stimulated through the CD2 pathway.
AB  - This study was designed to compare cytokine release in lamina propria lymphocytes
      (LPLs) and PBLs activated by Abs against CD3, CD2, and CD28. LPL T cells were
      significantly more responsive to CD2 ligation than PBL, as determined by release
      of IFN-gamma, IL-2, IL-4, and TNF-alpha. Moreover, CD28 co-ligation in LPLs
      exaggerated CD2 > CD3 dominance in cytokine induction. PHA-activated PBLs
      expressed more CD2 receptors than freshly isolated LPLs, but were less responsive
      to activation through CD2, indicating that postreceptor pathways in LPL may be
      adapted specifically to facilitate CD2-mediated cytokine secretion.
      Antiphosphotyrosine (APT) immunoblotting revealed inducible substrate
      phosphorylation during CD2, but not CD3, ligation in whole LPLs, as well as LPL
      derived T cell lines. PBLs cocultured with an irradiated B cell line, Daudi, and
      IL-2 for 5 days attained a CD2-dominant cytokine-secretion pattern with identical
      tyrosine phosphorylation profiles as freshly isolated LPL or LPL T cell lines.
      PHA-activated PBLs did not produce these tyrosine phosphorylation profiles. This
      suggests that B lymphocytes in the lamina propria may contribute to a T cell
      differentiation process in which CD2, possibly by potentiation of its
      postreceptor pathway, becomes a prominent receptor for induction of cytokine
      secretion.

PMID- 7529286
TI  - NK cell response to viral infections in beta 2-microglobulin-deficient mice.
AB  - Because class I MHC Ags have been implicated as modulators of target cell
      sensitivity to NK cell-mediated lysis, the regulation of virus infections and the
      fate of NK cells and their natural targets was examined in beta 2-microglobulin
      deficient mice, which have defective class I MHC expression. Infections with
      either the NK cell-sensitive murine cytomegalovirus (MCMV) or the NK cell
      resistant lymphocytic choriomeningitis virus (LCMV) significantly augmented NK
      cell activity in either C57BL/6 (+/+) or beta 2-microglobulin knockout (-/-)
      mice. Depletion of NK cells in vivo with antiserum to asialo-GM1 markedly
      enhanced the synthesis of MCMV but had no effect on the synthesis of LCMV in
      either strain of mouse. Analysis of naturally NK cell-sensitive thymocyte targets
      from these virus-infected -/- mice revealed no cell surface expression of class I
      MHC detectable by conformation-dependent or -independent Abs, but the virus
      infections enhanced class I expression on thymocytes from +/+ mice. The
      sensitivity of +/+ thymocytes to NK cell-mediated lysis was markedly reduced
      after in vivo poly inosinic:cytidylic and treatment or viral infection; in
      contrast, the sensitivity of the -/- thymocytes was significantly less affected
      by poly inosinic:cytidylic acid treatment or viral infection. These data indicate
      that the normal expression of class I MHC Ags on NK cells or their targets is not
      required for the antiviral functions of NK cells against a NK-sensitive virus
      (MCMV) nor do they protect a NK-resistant virus (LCMV) from the antiviral
      activity of NK cells.

PMID- 7529287
TI  - Conformation and ion channel activity of lymphotoxin at neutral and low pH.
AB  - Lymphotoxin (LT or TNF-beta), a T cell-derived lymphokine with partial homology
      to TNF-alpha, was found to bind to dimyristoylphosphatidylcholine vesicles in a
      pH-dependent manner: binding increased with decreasing pH. Binding was not
      limited to surface association with phospholipid head groups because studies with
      a photoreactive membrane-restricted probe revealed protein penetration of the
      hydrocarbon core of the bilayer. Intramembranous photolabeling of the trimeric
      form of LT demonstrated maintenance of quaternary structure upon bilayer
      insertion. The efficiency of insertion was greatly enhanced with gel-phase
      bilayers compared with fluid phase bilayers even though the binding efficiency
      was much lower. Hence, binding and insertion represent two distinct physical
      processes. Intrinsic fluorescence and dye binding assays showed that the acid
      facilitated membrane interactions stemmed from acid-induced changes in protein
      conformation. The acquisition of hydrophobic characteristics through these
      conformational changes supplies a physical explanation for LT conversion from a
      water-soluble form to a membrane-embedded structure. Moreover, the use of vesicle
      embedded LT to prepare planar bilayers vs the addition of soluble LT subsequent
      to bilayer formation demonstrated that LT exhibits channel activity and that low
      pH-induced membrane insertion precedes and is distinct from expression of voltage
      dependent ion gating. LT's ability to associate intimately with lipid vesicles
      and form ion channels mirrors the behavior of TNF-alpha. Thus, although LT and
      TNF-alpha are secreted by different cell types, the conservation of membrane
      binding, insertion, and channel-forming activities suggests a functional role in
      response induction.

PMID- 7529289
TI  - Activation of human monocytes by streptococcal rhamnose glucose polymers is
      mediated by CD14 antigen, and mannan binding protein inhibits TNF-alpha release.
AB  - The present work was initiated to define mechanisms that account for the binding
      on human monocytes of streptococcal cell wall polysaccharides formed by rhamnose
      glucose polymers (RGPs), and subsequent stimulatory activities. We show here that
      RGPs bind to and stimulate human monocytes to produce TNF-alpha in a dose
      dependent manner. To detect cell surface RGPs binding proteins, intact monocytes
      were biotinylated before lysis with Nonidet P-40 and solubilized proteins were
      incubated with RGPs Affi-Prep beads. One major membrane protein of 55 kDa was
      specifically detected and identified as CD14 because it reacted with anti-CD14
      mAbs. Furthermore, anti-CD14 mAbs were able to perform a dose-dependent
      inhibition of RGPs binding, and suppressed TNF-alpha release from RGPs-stimulated
      monocytes. Moreover, we demonstrated that RGPs also bind to CD11b; however, this
      binding is not implicated in synthesis of TNF-alpha. Interestingly, RGPs binding
      to monocytes was enhanced by human normal serum (HNS) whereas HNS inhibits the
      TNF-alpha-stimulating activity of RGPs. Western blotting analysis of HNS proteins
      purified on RGPs Affi-prep beads revealed three specific bands of 75, 55, and 32
      kDa reactive with anti-C3 Abs, anti-CD14 mAbs (TUK4), and anti-human mannan
      binding protein (hMBP)-derived peptide IgG, respectively. These results suggest
      that C3, soluble CD14, and hMBP form complexes that are probably active in
      enhancing the binding of RGPs to monocytes. Additional studies have shown that
      hMBP that recognizes RGPs prevents, unlike the LPS binding protein, TNF-alpha
      release by inhibiting the binding of RGPs to CD14 Ag. By incubating cells with a
      constant amount of RGPs-hMBP complexes in the presence or absence of increasing
      concentrations of C1q, we also demonstrated that C1q receptor mediates the
      binding and probably the uptake of RGPs-hMBP complexes by human monocytes.

PMID- 7529288
TI  - IL-13 selectively induces vascular cell adhesion molecule-1 expression in human
      endothelial cells.
AB  - Previous studies with human umbilical vein endothelial cells (HUVEC) have shown
      that the cytokine IL-4 induces adherence of human eosinophils, but not
      neutrophils, because of its ability to selectively induce surface expression of
      vascular cell adhesion molecule-1 (VCAM-1). Because the cytokine IL-13 shares a
      number of biologic properties with IL-4, we examined the effect of IL-13 on the
      expression and function of adhesion molecules on HUVEC. Incubation of HUVEC for 4
      to 48 h with IL-13 (0.1 to 15 U/ml) induced surface expression of VCAM-1, as
      detected by indirect immunofluorescence and flow cytometry, without significantly
      affecting expression of E-selectin or intercellular adhesion molecule-1. The
      kinetics and maximal IL-13-induced expression of VCAM-1 were similar to those
      seen with IL-4. Treatment of HUVEC with an optimal concentration of IL-13 (15
      U/ml for 24 h) induced adhesiveness for eosinophils, but not for neutrophils, and
      adhesion was completely inhibited by mAb recognizing VCAM-1 or alpha 4 integrin
      (CD49d). These results demonstrate that IL-13, like IL-4, selectively stimulates
      HUVEC to express functional cell surface VCAM-1 and suggest a possible role for
      IL-13 in promoting VCAM-1/alpha 4 integrin-dependent accumulation of eosinophils
      during allergic and other inflammatory reactions in vivo.

PMID- 7529291
TI  - Increased severity of experimental autoimmune encephalomyelitis in rats tolerized
      as adults but not neonatally to a protective TCR V beta 8 CDR2 idiotope.
AB  - The ability of synthetic V region peptides to induce regulatory T cells and Abs
      in rodents and humans provides clear evidence that these idiotopes do not
      naturally induce tolerance. In this study, we investigated the ability of TCR V
      beta 8.2 peptides to experimentally induce specific T cell tolerance, as measured
      by loss of Ag-specific proliferation and delayed-type hypersensitivity responses,
      and by increased susceptibility to experimental autoimmune encephalomyelitis
      (EAE). We found that both neonatal and adult exposure to V beta 8.2-39-59 or V
      beta 8-44-54 peptides could induce efficient T cell tolerance, resulting in a
      significant inhibition of peptide-specific proliferative responses. In addition,
      neonatal tolerance resulted in a partial reduction in delayed-type
      hypersensitivity response and an inability to vaccinate against EAE after adult
      immunization with the tolerizing peptide. We further evaluated the contribution
      of naturally induced TCR-specific responses to EAE resistance induced by
      challenging neonatally or adult tolerized rats with myelin basic protein in
      adjuvant. The clinical course of EAE was not significantly altered in rats
      tolerized neonatally to V beta 8.2 peptides, but both the severity and incidence
      of mortality from EAE was increased in rats tolerized as adults with V beta 8.2
      peptides conjugated to syngeneic splenocytes. These results demonstrate that V
      beta 8.2 peptides are tolerogenic as well as immunogenic. Moreover, the
      observation of different effects of neonatal vs adult tolerization on the course
      of EAE suggests either the emergence of additional protective idiotopes after
      neonatal tolerization and/or mechanistic differences in the two tolerance
      inducing protocols. Most importantly, the enhancement of clinical EAE in rats
      tolerized as adults with V beta 8.2 peptides provides evidence for an innate
      regulatory role of the CDR2 idiotope in recovery from EAE.

PMID- 7529290
TI  - Neutralizing recombinant human antibodies to a conformational V2- and CD4-binding
      site-sensitive epitope of HIV-1 gp120 isolated by using an epitope-masking
      procedure.
AB  - As part of the goal of assembling a mixture of neutralizing human mAbs for
      possible prophylaxis and therapy of HIV-1 disease, we describe a strategy by
      which neutralizing human Abs to a weakly immunogenic epitope can be accessed.
      From a phage display library derived from an asymptomatic HIV-1 seropositive
      donor, a panel of recombinant Fabs against the CD4 binding site (CD4bs) of gp120
      was retrieved by affinity selection using recombinant gp120 (strain LAI). Two
      Fabs corresponding to the dominant clones were used to mask the CD4bs epitope(s)
      before repeating the selection procedure. Four Fabs were then retrieved that had
      novel heavy chain sequences. Three recognized a novel epitope distinct from that
      recognized by conventional CD4bs Abs and were defined by the following criteria:
      1) second V region (V2 region) dependence indicated by sensitivity to amino acid
      changes in the V2 loop and by competition with murine anti-V2 mAbs; 2) CD4bs
      dependence indicated by sensitivity to amino acid changes usually associated with
      CD4 binding and by inhibition of Fab binding to gp120 by soluble CD4; this
      dependence seemed to arise via conformational changes rather than by direct
      binding, as CD4bs Abs enhanced binding of two of the novel Fabs and, in a
      reversal of the competition format, the novel Fabs did not inhibit soluble CD4
      binding to gp120; and 3) equivalent binding to glycosylated and deglycosylated
      gp120 and significant, although much reduced, binding to denatured gp120 in
      contrast with CD4bs Abs, which do not bind to deglycosylated or denatured gp120.
      One of the novel Fabs efficiently neutralized the MN and LAI strains of HIV-1.
      These results indicate the presence of a novel neutralizing conformational
      epitope on gp120 sensitive to the V2 loop and the CD4bs and further highlight the
      conformational flexibility of gp120. The strategy of masking highly immunogenic
      epitopes with Abs to rescue a broader range of specific Abs from combinatorial
      libraries should be widely applicable.

PMID- 7529292
TI  - Apoptosis abnormalities of splenic lymphocytes in autoimmune lpr and gld mice.
AB  - The murine gene lpr encodes an aberrant form of the apoptosis-inducing receptor
      Fas. The gene gld, which causes an autoimmune syndrome phenotypically identical
      to that caused by lpr, encodes a mutant Fas ligand. Because the lpr gene must be
      expressed in both T and B cells to produce autoimmune disease, it might be
      anticipated that apoptosis abnormalities would be present in both. Therefore, we
      quantitated apoptosis in T and B cells from lpr, gld, and normal mice in a short
      term in vitro culture system. Freshly isolated spleen cells from normal, lpr, or
      gld mice showed little or no apoptosis as assessed by quantitative DNA flow
      cytometry. However, after overnight culture, both T and B cells showed
      substantial spontaneous apoptosis. Such apoptosis increased strikingly with age
      in normal but not in autoimmune B cells. CD23low B cells, which are prominent in
      lpr and gld mice, were particularly notable for high levels of programmed cell
      death in normal mice. The apoptosis caused by the gld defect could not be
      corrected by coculture with normal spleen cells. The persistence with age of low
      levels of B cell apoptosis in lpr and gld mice presumably reflects deficient
      Fas/Fas ligand interactions. The further localization of the B cell apoptosis
      defect to the unusual CD23low B cells, which accumulate in lpr and gld mice, adds
      to the evidence that these cells may be of critical importance to autoimmunity.

PMID- 7529294
TI  - [Kidney disorders induced by immunosuppressive agents].

PMID- 7529293
TI  - Analysis of the autoantibody response to fibrillarin in human disease and murine
      models of autoimmunity.
AB  - Fibrillarin, a component of the U3 RNP particle, is a target for the
      spontaneously arising autoantibodies in human scleroderma and a monoclonal
      autoantibody (72B9) derived from the autoimmune mouse strain (NZB x NZW) F1.
      Autoantibodies against fibrillarin can also be induced in H-2s mice by treatment
      with mercuric chloride (HgCl2). The objective of this study was to compare the
      spontaneously occurring anti-fibrillarin autoantibody response with the
      autoantibody response induced by HgCl2 treatment. Immunofluorescence microscopy
      on human HEp2, mouse 3T3, and Xenopus XIK-2 cells, immunoblotting with use of
      nuclear extract from human MOLT-4, mouse 3T3, and Xenopus XIK-2 cells, and
      immunoprecipitation with use of in vitro translation products of RNA transcripts
      from yeast fibrillarin cDNA were used in this analysis. Both spontaneous and
      induced autoantibodies displayed common reactivity in that, irrespective of the
      antigenic source, they gave the same nucleolar immunofluorescence pattern and a
      restricted immunoblotting reactivity targeting predominantly the 34-kDa protein
      fibrillarin. Immunoprecipitation of N- and C-terminal truncated fibrillarin
      constructs also demonstrated a common pattern of reactivity. All Abs precipitated
      a fragment comprising amino acids 1-312 but not a smaller fragment containing
      amino acids 1-257. The majority of sera could not precipitate an N-terminal
      truncated molecule consisting of amino acids 157-327. These immunoprecipitation
      experiments support recognition of a common epitope requiring both N- and C
      regions, which may be exemplified by the reactivity of murine monoclonal anti
      fibrillarin autoantibody 72B9. Our results indicate that spontaneous human and
      toxin-induced murine autoantibodies to fibrillarin share common reactivity
      against this highly conserved nucleolar protein.

PMID- 7529295
TI  - DNA damage in bromodeoxyuridine substituted SV40 DNA and minichromosomes
      following UVA irradiation in the presence of Hoechst dye 33258.
AB  - Bromodeoxyuridine-substituted SV40 DNA and SV40 minichromosomes were prepared
      from infected CV1 cells, and exposed to UVA light in the presence of different
      concentrations of Hoechst dye 33258. Following agarose gel electrophoresis, the
      yields of ssbs and dsbs were determined. In DNA these yields are dependent on the
      level of BrdU substitution (0.038 ssb and 0.00022 dsb per BrdU residue/kJm-2),
      and on the mode of dye binding (type I versus II). The yields of both ssbs and
      dsbs were found to be lower by factors of 1.25 and 2 respectively in
      minichromosomes. UVA irradiation in the presence of the thiol cysteamine results
      in lower strand break yields, presumably due to the repair of DNA radicals formed
      during photolysis. The thiol was found to react seven times more slowly with the
      DNA radicals than oxygen. The implications of these results are discussed in
      light of prior cellular studies.

PMID- 7529296
TI  - Anti-beta 1 integrin antibody inhibits Schwann cell myelination.
AB  - Schwann cells (SCs) co-cultured with sensory neurons require ascorbate
      supplementation for basal lamina assembly and differentiation into myelinating
      cells. The ascorbate requirement can be bypassed by adding a purified basal
      lamina component, laminin, to SC/neuron co-cultures. We have examined the role of
      laminin receptors, namely, the beta 1 subfamily of integrins, in the process of
      myelination. We demonstrate by immunostaining or immunoprecipitation that
      undifferentiated SCs in contact with axons express large amounts of the beta 1
      subunit in association with the alpha 1 or alpha 6 subunit. In co-cultures of
      myelinating SCs, alpha 1 beta 1 is no longer present, alpha 6 beta 1 is still
      present but at reduced levels, and alpha 6 beta 4 is expressed at much higher
      levels than in co-cultures of undifferentiated SCs. Immunogold labelling at the
      electron microscope level suggested that beta 1 integrins are randomly
      distributed on undifferentiated SCs, become localized to the SC surface
      contacting basal lamina in differentiating SCs before the onset of myelination,
      and are not detected on myelinating SCs. Fab fragments of beta 1 function
      blocking antibody block both attachment of isolated SCs to laminin and formation
      of myelin sheaths by SCs co-cultured with neurons in ascorbate-supplemented
      medium. SCs unable to myelinate in the presence of the anti-beta 1 antibody
      assemble patchy basal lamina that is only loosely attached to the cell surface
      and in some cases appears to be detaching from the membrane. In contrast, an
      alpha 1 beta 1 function-blocking antibody only partially blocks attachment of
      isolated SCs to laminin but has no inhibitory effect on SC myelination. These
      results are consistent with the hypothesis that a member of the beta 1 subfamily
      of integrins other than alpha 1 beta 1 binds laminin present in basal lamina to
      the SC surface and transduces signals that are critical for initiation of SC
      differentiation into a myelinating cell.

PMID- 7529297
TI  - Unexpected expression of intermediate filament protein genes in human
      oligodendroglioma cell lines.
AB  - From a human oligodendroglioma cell line cDNA library, ten intermediate filament
      (IF) cDNA clones were isolated. Five clones corresponded to vimentin mRNA, two
      corresponded to cytokeratin K7 mRNA, and two corresponded to cytokeratin K8 mRNA.
      One clone encoded a novel IF mRNA. The expression of these and other IF protein
      genes was examined in five cell lines derived from human oligodendroglioma,
      astrocytoma and neuroblastoma tumors. Vimentin mRNA and K18 mRNA were expressed
      in all the cell lines. The K7 and K8 genes were expressed only in the
      oligodendroglioma cell lines. Surprisingly, nestin mRNA was expressed in the
      astrocytoma lines and the neuroblastoma line, but was not expressed in the
      oligodendroglioma lines. These results indicate that oligodendroglioma cell lines
      express Types I and II cytokeratin genes. This pattern of IF gene expression was
      different from that of the astrocytoma and neuroblastoma cell lines, which
      expressed IF genes usually associated with the mature cell types or with
      differentiating fetal neural precursor cells, i.e. GFAP and neurofilament-L. The
      results also suggest that the oligodendroglioma cell lines are more epithelial in
      character and do not reflect the gene expression of mature oligodendrocytes.

PMID- 7529299
TI  - Substance P, neurofilament, peripherin and SSEA4 immunocytochemistry of human
      dorsal root ganglion neurons obtained from post-mortem tissue: a quantitative
      morphometric analysis.
AB  - Immunocytochemical studies on lumbar dorsal root ganglia obtained at routine
      postmortem 24-36 h after death were carried out, and neuronal cross-sectional
      areas measured. The subjects were elderly (76-81 years), of both sexes, had died
      from heart attack or haemorrhage, and had no clinical evidence of clinical
      neuropathy or of disease known to be associated with neuropathy. The data were
      consistent between ganglia from the three subjects. There were striking
      similarities with data from other species. Two populations of cell profiles with
      overlapping size distributions were distinguished with an anti-neurofilament
      antibody, neurofilament-rich (45% of cell profiles) with a large mean area and
      neurofilament-poor with a smaller mean area. Anti-substance P and anti-peripherin
      antibodies both labelled a population with a small mean area, with extensive co
      localization between them. There were also some differences between these human
      dorsal root ganglia and dorsal root ganglia from some other species. More
      neuronal profiles were labelled for substance P in humans (44%) than in rat
      (20%). More neuronal profiles were labelled for SSEA4 (stage specific embryonic
      antigen 4) in human (40.5%) than in rat dorsal root ganglia (10%), and the SSEA4
      positive profiles were relatively smaller in human than in rat. No selective
      accumulation of lipofusin in profiles of large cells was apparent. This study
      also shows that quantitative morphometric analysis of immunocytochemically
      labelled dorsal root ganglion neuronal profiles can be carried out successfully
      on human sensory ganglia obtained at post-mortem. This is the first demonstration
      of the two main subgroups of dorsal root ganglia neurones with neurofilament-rich
      and poor somata in human tissue. The size distributions of neurons with
      neurofilament, substance P and peripherin are consistent with these neuronal
      populations having similar functional properties to those described in other
      species. From the known sensory and fibre loss with aging, it is speculated that
      the loss of some large diameter neurones with myelinated fibres and low
      mechanical thresholds, might account for the high percentage of neurones
      expressing substance P.

PMID- 7529298
TI  - Experimental induction of myelin changes by anti-MAG antibodies and terminal
      complement complex.
AB  - We investigated the role of anti-myelin-associated glycoprotein (MAG) IgM and
      complement (C) in the pathogenesis of myelin alterations occurring in patients
      with anti-MAG-associated polyneuropathy. For this purpose, we separately studied
      the effects of anti-MAG antibodies and terminal C complex (TCC) after injection
      into the rabbit sciatic nerve. The two different local treatments produced
      identical ultrastructural abnormalities such as intramyelinic edema, myelin
      vesiculation and, in particular, separation of the major dense lines with the
      formation of widely spaced myelin, a peculiar feature encountered in human
      peripheral nerve disorders with circulating anti-myelin monoclonal IgM. In nerves
      treated with anti-MAG IgM ultrastructural myelin alterations were concurrent with
      activation of the rabbit's own C to the formation of TCC. Contrary to the
      immunological and ultrastructural findings obtained in C-sufficient animals, in
      C6-deficient rabbits injected with anti-MAG IgM no myelin alterations nor C
      completion were observed. This study identifies anti-MAG IgM as the mediator and
      the C as the effector of myelin changes observed in the present model and, for
      extension, in human neuropathies associated with anti-MAG IgM.

PMID- 7529300
TI  - Focal brain injury and upregulation of a developmentally regulated extracellular
      matrix protein.
AB  - Tenascin is an extracellular matrix glycoprotein expressed during both normal
      development and neoplastic growth in both neural and nonneural tissues. During
      development of the central nervous system (CNS), tenascin is synthesized by glial
      cells, in particular by immature astrocytes, and is concentrated in transient
      boundaries around emerging groups of functionally distinct neurons. In the mature
      CNS, only low levels of the glycoprotein can be detected. The present study
      demonstrates that following trauma to the adult human cerebral cortex, discrete
      populations of reactive astrocytes upregulate their expression of tenascin and
      dramatically increase their transcription of the tenascin gene. The enhanced
      expression of tenascin may be involved in CNS wound healing, and may also affect
      neurite growth within and around a brain lesion.

PMID- 7529301
TI  - Coagulopathy with the use of hetastarch in the treatment of vasospasm.
AB  - The use of colloid agents to achieve hypervolemia in the prevention and treatment
      of postsubarachnoid hemorrhage (post-SAH) vasospasm is included in the standard
      of care at many institutions. Risk profiles are necessary to ensure appropriate
      use of these agents. In a series of 85 patients with recent aneurysmal SAH, 26
      developed clinical symptoms of vasospasm. Fourteen of the 26 were treated with
      hetastarch for volume expansion while the other 12 received plasma protein
      fraction (PPF). Clinically significant bleeding pathologies were noted in six
      patients who received hetastarch as a continuous intravenous infusion. Hetastarch
      increased partial thromboplastin time from a mean of 23.9 seconds to a mean of
      33.1 seconds (p < 0.001) in all patients who received infusions of this agent,
      while no effect was noted in the 12 patients who received PPF infusions. No other
      coagulation parameters were altered. This study shows an increase in coagulopathy
      with the use of hetastarch as compared with the use of PPF for the treatment of
      postaneurysmal vasospasm.

PMID- 7529302
TI  - Nitric oxide synthase and guanylate cyclase levels in canine basilar artery after
      subarachnoid hemorrhage.
AB  - Endothelium-dependent vasodilation may be impaired during cerebral vasospasm
      following subarachnoid hemorrhage. Under normal circumstances nitric oxide (NO)
      released by endothelial cells induces relaxation of smooth muscle by activating
      the soluble form of guanylate cyclase within muscle cells. In this study the
      levels of both endothelial NO synthase, the enzyme that produces NO, and soluble
      guanylate cyclase were determined in canine basilar arteries in a double
      hemorrhage model using Western blot immunoassays. Thirty dogs were assigned to
      three groups: Group D0, control; Group D2, dogs sacrificed 2 days after cisternal
      injection of blood; and Group D7, dogs given double cisternal injections of blood
      and sacrificed 7 days after the first injection. Constriction of the basilar
      artery was confirmed by arterial angiography. Portions of the affected arteries
      or the corresponding region in control animals were solubilized for sodium
      dodecylsulfate-polyacrylamide gel electrophoresis and Western blotting. A
      specific monoclonal antibody against endothelial NO synthase was used. The
      extract from basilar arteries showed two bands on the blots: 135 kD,
      characteristic of endothelial NO synthase, and 120 kD, which may be a degradation
      product of the enzyme. The densitometer values of the bands were presented as
      percentages of D0 control values. Although the total signal in the D7 group was
      less than that of the D0 control group (D2, 97% +/- 22%; D7, 78% +/- 40%), it was
      not statistically significant. The proportion of the 135-kD form decreased
      between Groups D0 and D7, but the difference was not significant. A single major
      band corresponding to the alpha-subunit of soluble guanylate cyclase was seen at
      70 kD in the basilar artery extracts. The signals of D2 and D7 samples were 69%
      +/- 40% and 25% +/- 18%, respectively. There was a significant difference between
      D7 and D0 (p < 0.001). The reduced expression of soluble guanylate cyclase may be
      related to the impairment of endothelium-dependent vasodilation in vasospasm.

PMID- 7529303
TI  - Overt vitamin B-6 deficiency affects rat pancreatic digestive enzyme and
      glutathione reductase activities.
AB  - Previous reports suggest that vitamin B-6 deficiency contributes to pancreatic
      insufficiency. However, the susceptibility of pancreatic function to marginal
      vitamin B-6 intake has not been defined. The present study examines digestive
      enzyme activity and steady-state mRNA levels, as well as antioxidant enzyme
      status from rats fed different vitamin B-6 diets. Groups (n = 12) of adult female
      Long-Evans rats were assigned to five dietary groups and fed their respective
      diets for 6 wk. Control and food-restricted rats were fed the control diet (7 mg
      pyridoxine/kg diet) freely, or food intake was restricted to the lowest intake of
      the experimental groups. The experimental groups were fed purified diets
      containing 0 (deficient), 0.25 or 1 (marginal) mg pyridoxine/kg diet. Plasma
      amylase and pancreatic amylase, trypsin and chymotrypsin activities were
      significantly lower in deficient rats compared with rats fed the control diet.
      Lower enzyme activities were accompanied by 83 and 55% lower amylase and
      trypsinogen mRNA levels compared with levels in rats fed the control diet. Other
      than low glutathione reductase in deficient rats, pancreatic antioxidant enzyme
      activity was similar in all dietary groups. These data suggest that the exocrine
      pancreas is impaired by vitamin B-6 deficiency, but marginal pyridoxine intake
      maintains function.

PMID- 7529305
TI  - Effects of Si-functional isocyanate on the stability of oil-in-water emulsion
      with and without a carbon functional isocyanate.
AB  - The effects of silicon-functional isocyanates on the stability of oil-in-water
      emulsions with and without a carbon functional triisocyanate in the oil phase
      were investigated. The oil component was di-n-butyl-phthalate (DBP) containing
      Aerosol OT as an emulsifier. It was found that only CH3Si(NCO)3 among the
      (CH3)nSi(NCO)4 - n's was effective to contribute additional stability for the
      emulsion without a carbon functional triisocyanate. It was also found that a
      reaction product of CH3Si(NCO)3 with water reacted with a carbon functional
      triisocyanate.

PMID- 7529304
TI  - Developmental regulation of the porcine exocrine pancreas by glucocorticoids.
AB  - The possible role of cortisol in development of the exocrine pancreas was
      investigated. In the first study, fetal pigs were removed from the uterus by
      caesarean section (pentobarbitone anesthesia) and the pancreas collected from 51
      69 to 109-day-old fetuses (term = 114 +/- 2 days). Of these, 15 88 to 90-day-old
      fetuses had been infused subcutaneously for 6 days with either saline,
      adrenocorticotropic hormone or cortisol (osmotic mini-pumps implanted at 82-84
      days). The pancreas was also removed from eight newborn pigs. Quantitative enzyme
      analysis showed that amylase and trypsin activities per milligram pancreatic
      protein increased toward term, correlated positively with fetal plasma cortisol
      (p < 0.01) and were stimulated by cortisol infusion (p < 0.05). In the second
      study, pigs were delivered by caesarean section 2-3 days before term (to
      circumvent the neonatal cortisol surge) and injected intramuscularly with saline
      (n = 11), metyrapone (an inhibitor of cortisol synthesis, n = 12),
      adrenocorticotropic hormone (n = 14) or cortisol acetate (n = 6) during the
      postnatal period. At 6-7 days of age, adrenocorticotropic hormone- and cortisol
      acetate-treated pigs had higher concentrations of amylase and trypsin in pancreas
      than metyrapone-treated pigs. The values in saline-injected pigs were
      intermediate. By gel electrophoresis and subsequent incubation with enzyme
      substrates, protease E, chymotrypsin C, and cathodic trypsin were first detected
      at 6-7 days of age, and the activities (semiquantitative densitometry) appeared
      lower in metyrapone-treated pigs than in pigs from other treatment groups. The
      results indicate that glucocorticoids stimulate the perinatal development of
      pancreatic enzymes in the pig.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529306
TI  - Menthol and related cooling compounds.
AB  - Menthol and related cooling compounds such as 'coolant agent 10', are widely used
      in products ranging from common cold medications to toothpastes, confectionery,
      cosmetics and pesticides. The review brings together a range of information on
      production and chemistry of menthol, and its metabolism, mechanism of action,
      structure-activity relationships, pharmacology and toxicology. In particular, the
      coolant action and carminative actions of menthol are discussed in terms of
      actions on calcium conductance in sensory nerves and smooth muscle. The actions
      of menthol on the nose, respiratory reflexes, oral cavity, skin and
      gastrointestinal tract are reviewed.

PMID- 7529307
TI  - Differential effects of L-NAME on blood pressure and heart rate responses to
      acetylcholine and bradykinin in cynomolgus primates.
AB  - NG-nitro-L-arginine methyl ester (L-NAME) has been reported to have variable
      effects on the vasodilator response to acetylcholine (ACh) and bradykinin (BK) in
      vivo. Whether administration of L-NAME affects mean arterial pressure (MAP) or
      heart rate (HR) responses to ACh or BK was examined in conscious cynomolgus
      primates. ACh (0.1-10 micrograms/kg i.v.) lowered MAP by 6% to 37%, responses
      which were inhibited (25-62%) in the presence of L-NAME (1-100 mg/kg i.v.).
      Although L-NAME increased MAP similarly at doses of 10 and 100 mg/kg, only the
      100-mg/kg dose inhibited the hypotensive responses induced by the higher doses of
      ACh. By comparison, nitroprusside (5 micrograms/kg i.v.)-induced hypotensive
      responses were not inhibited by L-NAME. Phenylephrine (20 micrograms kg-1 min-1
      i.v.) increased MAP and lowered HR to levels statistically similar to that of L
      NAME but did not alter ACh-induced hypotensive responses. ACh dose-dependently
      decreased HR, both in the absence and presence of L-NAME or phenylephrine. In
      pentobarbital-anesthetized monkeys, ACh-induced hypotensive responses were
      inhibited by 75% to 94% in the presence of L-NAME; BK (0.3-1 microgram/kg i.v.)
      responses were only modestly affected (< or = 50%). Therefore, in conscious
      primates, L-NAME affects the basal release of nitric oxide (NO) at lower doses
      than those required to inhibit its release stimulated by ACh. Also, L-NAME does
      not appear to act as a cholinergic antagonist or affect the functional mechanisms
      that control baroreflex responses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529308
TI  - 3-Isobutyl-1-methylxanthine increases alpha-1-adrenergic receptor sensitivity and
      density in DDT1-MF2 smooth muscle cells.
AB  - The effect of chronic exposure of DDT1-MF2 smooth muscle cells to the
      phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) was investigated
      with regard to the dynamics of alpha-1-adrenergic receptors. After 48 hr of
      exposure to 750 microM IBMX, the magnitude of the maximal phospholipase C
      response to norepinephrine was increased approximately 2-fold and the potency of
      norepinephrine was increased almost 3-fold. Similar effects were noted for the
      response to ATP. The density of alpha-1-adrenergic receptors, as defined by [3H]
      prazosin binding to membranes was increased 2-fold. In addition, chronic
      treatment with IBMX prevented agonist-induced desensitization of alpha-1
      adrenergic receptors and enhanced the rate of receptor resensitization subsequent
      to desensitization by a combination of agonist and phorbol ester. These effects
      appear to be regulated by a cyclic AMP-dependent mechanism. Thus, chronic
      exposure of smooth muscle cells to phosphodiesterase inhibition may activate
      compensatory mechanisms that lead to enhanced sensitivity to contractile stimuli.
      The potential importance of such compensatory mechanisms in the treatment and
      etiology of smooth muscle dysfunction is briefly discussed.

PMID- 7529309
TI  - Interaction of galanin fragments with galanin receptors on isolated smooth muscle
      cells from guinea pig stomach: identification of a novel galanin receptor
      subtype.
AB  - From structure-function studies it has been proposed that two subtypes of
      receptors may mediate galanin's actions in the gastrointestinal tract and other
      tissues and their effects can be either direct or neurally mediated. We have
      recently demonstrated that isolated gastric smooth muscle cells possess high
      affinity galanin receptors, activation of which increases AMP and causes
      relaxation. Because this cell system contains no neural elements, contains a
      single class of galanin receptors and allows binding to be correlated with
      function, it is a good system to investigate peptide requirements for cell
      activation. Porcine galanin (p-Gal) and rat galanin (r-Gal) were equipotent to
      the NH2-terminal fragments r,p-Gal(1-10), r,p-Gal(1-15), r,p-Gal(1-20), p-Gal(2
      29) and p-Gal(3-29) at inhibiting binding of 125I-galanin to gastric smooth
      muscle cells from guinea pig (Kd 5-8 nM). The midmolecule fragment p-Gal(9-25)
      and the long COOH-terminal fragment r-Gal(9-29) were equipotent and 25-fold less
      potent than p-Gal. Acetylation of r-Gal(9-29) increased potency to that of p-Gal.
      The short COOH-terminal fragment, p-Gal(21-29) and r-Gal(21-29), had very low
      affinity (Kd 3 microM). Each peptide alone (1 microM) caused no effect on cell
      length, but inhibited carbachol-induced contraction. The inhibition was 81% to
      92% for r-Gal or p-Gal, r,p-Gal(1-10), r,p-Gal(1-15), r,p-Gal(1-20), p-Gal(2-29),
      p-Gal(3-29) and Ac-r-Gal(9-29); 47% for p-Gal(9-25) and r-Gal(9-29); and 16% to
      17% for p-Gal(21-29).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529310
TI  - Isoproterenol causes hyperpolarization through opening of ATP-sensitive potassium
      channels in vascular smooth muscle of the canine saphenous vein.
AB  - Experiments were designed to determine how isoproterenol affects the cell
      membrane potential of smooth muscle cells of the canine saphenous vein.
      Measurements of membrane potential were performed using glass microelectrodes.
      Isoproterenol (10(-9) to 10(-6) M) caused sustained, concentration-dependent
      membrane hyperpolarizations in tissues with and without endothelium. ICI 118,551
      (a selective beta 2-adrenoceptor antagonist), but not atenolol (a selective beta
      1-adrenoceptor antagonist), abolished the hyperpolarization to isoproterenol.
      Forskolin, an activator of adenylate cyclase, produced sustained
      hyperpolarizations, which were not mimicked by 1,9-dideoxyforskolin. Incubation
      with either ouabain or extracellular K(+)-free solution did not inhibit the
      electrical response to isoproterenol. Glibenclamide (a selective ATP-sensitive K+
      channel antagonist) attenuated the hyperpolarizations induced by either
      isoproterenol or forskolin, whereas charybdotoxin (an inhibitor of large
      conductance Ca(++)-activated K+ channels) did not. These findings suggest that
      isoproterenol opens ATP-sensitive K+ channels indirectly through activation of
      adenylate cyclase in the smooth muscle of the canine saphenous vein. The
      adrenergic receptor involved belongs to the beta 2-adrenoceptor subtype.

PMID- 7529311
TI  - Cyclothiazide acts at a site on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid receptor complex that does not recognize competitive or
      noncompetitive AMPA receptor antagonists.
AB  - Activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA) subtype of ionotropic glutamate receptors by certain agonists, including
      AMPA and glutamate, has been shown to result in a rapid desensitization of the
      receptor. This desensitization is profoundly inhibited by the benzothiadiazide
      diuretic, cyclothiazide. We previously reported that cyclothiazide potentiates
      AMPA-induced [3H]norepinephrine ([3H]NE) release from rat hippocampal slices. We
      used this system to investigate the possible interaction of cyclothiazide with
      various AMPA receptor antagonists, including the competitive antagonist LY293558
      and the 2,3-benzodiazepine noncompetitive antagonist GYKI 53655. Cyclothiazide
      significantly potentiated both AMPA- and KA-induced [3H]NE release from slices of
      the rat hippocampus. LY293558 and GYKI 53655 inhibited the potentiated and
      nonpotentiated AMPA- and KA-induced [3H]NE release in a concentration-dependent
      manner. The IC50 values for inhibition of AMPA- or KA-induced [3H]NE release by
      either antagonist were not affected by the presence of cyclothiazide. Thus,
      cyclothiazide seems to interact at a site on the AMPA receptor complex which
      differs from either the glutamate recognition site or the 2,3-benzodiazepine
      allosteric site.

PMID- 7529312
TI  - Dilator prostanoid-induced cyclic AMP formation and release by cerebral
      microvascular smooth muscle cells: inhibition by indomethacin.
AB  - The effect of indomethacin on dilator prostanoid receptor-mediated cAMP formation
      was investigated using primary cultures of vascular smooth muscle cells from the
      newborn pig cerebral microvessels. Cerebral microvascular smooth muscle cells
      responded to dilator prostanoids (iloprost > PGE2) by increasing cAMP formation
      and release into the media (EC50 = 2 x 10(-8) M and 2 x 10(-7) M for iloprost and
      PGE2, respectively). Indomethacin inhibited iloprost- and PGE2-evoked increases
      in cAMP formation (IC50 = 10(-4) M) and release (IC50 = 10(-6) M) by
      microvascular smooth muscle cells (maximal inhibition 80-90%), whereas
      isoproterenol-induced cAMP formation was only slightly attenuated at the highest
      concentration of indomethacin used (10(-3) M). Aspirin was much less effective in
      inhibiting dilator prostanoid-induced cAMP formation and release by the cells.
      Direct analysis of prostacyclin receptor sites using [3H]iloprost as the ligand
      revealed saturable, high affinity (ED50 = 2 x 10(-8) M) and reversible binding to
      the membranes isolated from cerebrovascular smooth muscle cells. Indomethacin
      dose-dependently inhibited [3H]iloprost receptor binding (ID50 = 10(-4) M;
      maximal inhibition, 70%). The present data suggest that combination of highly
      effective inhibition of prostaglandin H synthase and receptor binding resulting
      in inhibition of dilator prostanoid-mediated cAMP formation in target cells may
      contribute to the increased efficacy of indomethacin compared with other
      prostaglandin H synthase inhibitors in blocking certain vasodilator responses
      associated with prostanoids.

PMID- 7529314
TI  - The immunosuppressant leflunomide inhibits lymphocyte progression through cell
      cycle by a novel mechanism.
AB  - Leflunomide is a novel and effective immunosuppressant that holds promise as a
      therapeutic agent, but the mechanism of action is unknown. Here we provide
      evidence that leflunomide is a general cytostatic agent for a wide range of
      cells. The IC50 for proliferation in transformed cell lines ranged from 2 to 16
      microM. The mean IC50 for proliferation of mitogen-stimulated rat lymphocytes (86
      nM) was much lower than for mouse (3.5 microM) or human (12.5 microM)
      lymphocytes. Initial signal transduction events (epidermal growth factor receptor
      stimulated phosphotyrosine formation and phytohemagglutinin-stimulated Ca++
      mobilization) were unaffected by antiproliferative concentrations of leflunomide.
      Leflunomide was equally as effective against mitogenic stimuli that bypass
      initial signaling events as it was against surface receptor-mediated mitogens.
      Leflunomide was fully potent when added 8 hr after the mitogenic stimulus.
      Cytokine dependent T-cell growth also was blocked by leflunomide. Leflunomide
      caused only partial reductions of autocrine cytokine production or cytokine
      receptor expression. Leflunomide blocked completely the progression of rat
      lymphocytes beyond early S-phase of cell cycle and inhibited entry of human T
      cells into the G2 and M-phases without causing cell death. Inhibition of
      proliferation could not be reversed by purine nucleosides. The results suggest
      that leflunomide's mechanism of action differs from that of other
      immunosuppressive agents such as corticosteroids, Cyclosporine A, rapamycin or
      mycophenolic acid.

PMID- 7529315
TI  - Histopathological changes in rabbit craniomandibular joint associated with
      experimentally induced anterior disk displacement (ADD).
AB  - Several studies have shown that anterior disk displacement (ADD) of human
      temporomandibular joint (TMJ) can lead to cellular and extracellular alterations
      in the disk proper, bilaminar zone (BZ), condyle, articular eminence and synovial
      membrane. Due to lack of an animal model for this disease, it is not known
      whether the mechanical displacement of the disk could lead to the observed
      histopathological changes. The purpose of this experiment was to investigate the
      histopathological changes that occur in the rabbit craniomandibular joint (CMJ)
      following surgical induction of ADD. The right CMJ was exposed surgically and the
      discal attachments were severed except for the BZ attachments. Then the disk was
      displaced anteriorly and sutured to the zygomatic arch. The left joint served as
      surgical control. The CMJs were removed after 24 h, 1 week, 2 weeks or 6 weeks
      and stained with H&E or modified Masson stain. The results showed
      neovascularization, cell clustering and fibrillation of the displaced disk. The
      BZ showed marked fibrosis. The condyle showed subchondral hemorrhage and fibrosis
      followed by osteoarthritic changes in the articular cartilage. The articular
      eminence showed chondrocytic clustering and an increase in the amount of
      chondroid bone. Synovial membrane exhibited marked hyperplasia. We concluded that
      surgical induction of ADD in the rabbit CMJ leads to cellular and extracellular
      alterations in the disk proper, BZ, condyle, articular eminence and synovial
      membrane similar to those described previously in human ADD. It appears that the
      mechanical trauma resulting from ADD could lead to a cascade of reparative and
      degenerative changes of the affected joints similar to those described for
      osteoarthritis.

PMID- 7529313
TI  - Lipopolysaccharide-induced hypotension and vascular hyporeactivity in the rat:
      tissue analysis of nitric oxide synthase mRNA and protein expression in the
      presence and absence of dexamethasone, NG-monomethyl-L-arginine or indomethacin.
AB  - The role of inducible nitric oxide synthase (iNOS) was examined in the
      hypotension and vascular hyporesponsiveness to norepinephrine (NE) invoked by
      lipopolysaccharide (LPS) in pentobarbital-anesthetized rats. Saline,
      dexamethasone (DEX), NG-monomethyl-L-arginine (LNMMA) or indomethacin (IND) were
      administered either pre-LPS (0.5 hr) or post-LPS (4.5 hr) treatment. Rats were
      then challenged with NE 10 min before LPS injection and 1, 4, and 5 hr after LPS.
      Administration of LPS produced a biphasic hypotension: an immediate hypotension,
      which partially recovered within 15 min and was unaffected by any of the
      pretreatments; and a secondary, more prolonged hypotension which was attenuated
      by DEX, LNMMA and IND. The NE-induced pressor effects were significantly
      attenuated 1, 4 and 5 hr post LPS. Pretreatment with LNMMA or DEX significantly
      attenuated the LPS-induced NE hyporesponsiveness 4 and 5 hr post LPS. LNMMA was
      the only post-LPS treatment able to reverse the NE hyporesponsiveness. The LPS
      induced iNOS mRNA and protein expression was demonstrated in the liver, lung,
      spleen, heart, kidney and brain by Northern hybridization and Western blot
      analyses. Low levels of neuronal constitutive NOS mRNA and endothelial cell
      constitutive NOS mRNA were only detected in brain or myocardial tissue,
      respectively. Significant induction of iNOS mRNA and protein expression was also
      observed in the liver, lung and spleen of rats pretreated with DEX, LNMMA or IND.
      The continued expression of iNOS in the presence of a pharmacologically relevant
      dose of DEX suggests that DEX may not be an optimal pharmacological agent for
      defining the in vivo roles of iNOS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529316
TI  - Glandular odontogenic cyst: analysis of cytokeratin expression and
      clinicopathological features.
AB  - The glandular odontogenic cyst (GOC) is a rare odontogenic cyst which is still
      controversial in regard to classification, terminology, and origin. The first
      Japanese case of GOC is reported. Immunohistochemical examination for expression
      of cytokeratins and epithelial membrane antigen by monoclonal antibodies
      suggested that the lining epithelium was of odontogenic origin with metaplastic
      mucus-laden cells. We have reviewed the literature and compared the
      clinicopathological findings of the reported case of GOC with those of botryoid
      odontogenic cysts (BOC). The anatomical location, age range, and sex of GOC cases
      were very similar to those of BOC. GOC appears to be a multiocular and
      mucoepidermoid variant of non-keratinizing odontogenic cysts, which also includes
      BOC. GOC should be separated from the other types of odontogenic cyst and central
      mucoepidermoid tumours of salivary gland origin.

PMID- 7529317
TI  - An extra band within the human 9qh+ region that behaves like the surrounding
      constitutive heterochromatin.
AB  - An extra variant G band in a human 9qh+ region was analysed in normally condensed
      and 5-azacytidine undercondensed chromosomes. Fluorescence in situ hybridisation
      showed that specific, classical, alphoid and beta satellite DNA was not present.
      Nevertheless, this extra band behaves like the surrounding heterochromatin
      because (1) its chromatin fibres showed condensation inhibition after 5
      azacytidine treatment, as confirmed by electron microscopy, and (2) it was not
      affected by in situ digestion with the restriction endonucleases AluI and Sau3A.
      These results suggest that this variant band may correspond to euchromatin that
      has become inactivated by a position effect.

PMID- 7529318
TI  - A gene for pachyonychia congenita is closely linked to the keratin gene cluster
      on 17q12-q21.
AB  - Pachyonychia congenita (PC) is a group of hereditary syndromes which have in
      common a hypertrophic dystrophy of the distal nail, and are associated with a
      variety of additional features, notably various dyskeratoses of skin and mucous
      membranes. The pathology is unknown but the array of clinical features suggests
      the possibility of a keratin abnormality. In the present report we describe
      linkage analyses in a large PC pedigree of the Jackson-Lawler type, a subtype
      which is characterised by multiple epidermal cysts, hair abnormalities, and natal
      teeth. The disease locus in this family was found to be tightly linked to markers
      mapping within, or very close to, the keratin type I cluster at 17q12-q21;
      maximum lod scores for linkage of the disease to a KRT10 polymorphism and to
      D17S800, a marker known to be very tightly linked to KRT10, were respectively
      +4.51 and +7.73, both at theta = 0.00. Although always likely, our findings
      provide strong evidence of a keratin gene anomaly underlying an inherited
      disorder affecting epidermis, nail, hair, and mucosa. These findings permit
      testing to see if pachyonychia congenita shows any locus heterogeneity and
      suggest specific candidate keratin genes for mutation searching studies. In
      addition, they suggest a role for keratins in the phenomenon of natal dentition.

PMID- 7529319
TI  - A cluster of cystic fibrosis mutations in exon 17b of the CFTR gene: a site for
      rare mutations.
AB  - Intensive screening has improved our understanding of the profile of mutations in
      the CFTR gene in which more than 400 mutations have been detected to date. In
      collaboration with several European laboratories we are involved in such
      analysis. We have identified 14 new mutations in exon 17b of CFTR, having
      analysed 780 CF chromosomes, and have compared the frequency of mutations in this
      exon with that of other regions of the CFTR gene. The results obtained indicate
      an accumulation of mutations, not only in regions encoding the two nucleotide
      binding folds, but also in those encoding transmembrane domains of the CFTR gene,
      in particular exon 17b.

PMID- 7529320
TI  - An interstitial deletion of chromosome 7(q35).
AB  - We describe a patient with developmental delay, mild dysmorphic features, and
      monosomy of 7q35. Only one other patient with an interstitial deletion of this
      band has been previously reported. A review of clinical features of these two
      children did not show similarities in dysmorphic features. Reports of patients
      with other 7q interstitial deletions are listed.

PMID- 7529323
TI  - Water permeability properties of the ovarian oocytes from Bufo arenarum and
      Xenopus laevis: a comparative study.
AB  - The water permeability properties of ovarian oocytes from Xenopus laevis and Bufo
      arenarum, a toad species found in the Buenos Aires region, were studied. We
      report that: (i) the water osmotic permeability (Pf, cm/sec x 10(-4)) was
      significantly higher in Bufo (6 degrees C = 12.3 +/- 2.4; 18 degrees C = 20.8 +/-
      4.8) than in Xenopus oocytes (6 degrees C = 5.3 +/- 0.3; 18 degrees C = 6.2 +/-
      1.6). The corresponding water diffusion permeability values (Pd, cm/sec x 10(-4))
      were: Xenopus = 2.3 +/- 0.3 (6 degrees C) and 4.8 +/- 0.7 (18 degrees C); Bufo =
      2.7 +/- 0.4 (6 degrees C) and 6.0 +/- 0.5 (18 degrees C). (ii) Amphotericin B
      increased the Pf and Pd values. The observed delta Pf/delta Pd ratio was not
      significantly different from the expected results (n = 3), after amphotericin B
      incorporation in both species. This means that the influence of unstirred layers
      and other potential artifactual compounds did not significantly affect our
      experimental results. (iii) Preincubation with gramicidin during 12 hr induced a
      clear increase in the oocyte volume. After that, a hypotonic shock only slightly
      increased the oocyte volume. Conversely, a hypertonic challenge induced a volume
      change significantly higher than the one observed in control conditions. (iv)
      Mercury ions did not affect the osmotic permeability in Xenopus oocytes but
      clearly inhibited, in a reversible way, the osmotic permeability in oocytes from
      B. arenarum. (v) Mercury ions did not reduce Pd values in either
      species.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529321
TI  - Nuclear electrophysiology.

PMID- 7529322
TI  - cAMP-enhancing agents "permit" stimulus-secretion coupling in canine pancreatic
      islet beta-cells.
AB  - Isolated canine islets of Langerhans differ from isolated islets of other species
      (including rodents and man) in that elevated glucose concentrations are unable to
      stimulate insulin secretion. Here we demonstrate that addition to the perifusate
      of isobutylmethylxanthine (IBMX), forskolin or 8-CPT-cAMP, all of which enhance
      cytosolic cAMP, permits insulin secretion in response to glucose, leucine or
      tolbutamide. These cAMP enhancers increase secretogogue-induced electrical
      activity in beta-cells and restore depolarization-induced, Ca(2+)-dependent
      granule exocytosis measured as stepwise increases in membrane capacitance. We
      propose that the primary permissive action of cAMP is to tightly link Ca2+ entry
      to insulin granule release, while a secondary action is to tighten the link
      between glucose metabolism and cell depolarization.

PMID- 7529326
TI  - D2 dopamine receptor protein location: Golgi impregnation-gold toned and
      ultrastructural analysis of the rat neostriatum.
AB  - The neostriatal distribution of D2 dopamine receptor protein has been assessed
      using subtype-selective polyclonal antibodies generated against three unique
      polypeptide sequences of the receptor. The experimental tissues were processed by
      peroxidase based immunohistochemical procedures for routine light microscopy,
      Golgi impregnation-gold toned morphological characterization, and correlative
      light/electron microscopy. The results demonstrated a regional gradient of D2
      like dopamine receptor expression in the neostriatum, where lateral portions in
      the nucleus exhibited more reactive cell bodies than medial portions. D2-like
      expression was detected in the three populations of neostriatal neurons, i.e.,
      the medium-sized spiny projection neurons, and the medium- and large-sized aspiny
      interneuron types. Morphometric measurements of labeled neurons verified that
      medium and large diameter neurons expressed the D2-like receptor subtype. D2-like
      immunoreactivity was distributed throughout the cytoplasm in dendritic processes,
      and in presynaptic terminal boutons. Immunoreactivity for the receptor protein
      was also detected in small, thinly myelinated axons, suggesting the possibilities
      of anterograde transport of the receptor from cell bodies in the substantia nigra
      to their neostriatal terminal fields, as well as from local axon collaterals of
      neostriatal projections neurons. These findings provide evidence of widespread
      distribution of the D2-like receptor protein in neostriatal neurons, and showed
      that the presynaptic D2 receptors contain analogous epitopes to the postsynaptic
      receptor subtype.

PMID- 7529324
TI  - Age-related quinidine effects on ionic currents of rabbit cardiac myocytes.
AB  - Age-related cardiac actions of quinidine have been shown in prolongation of
      action potential duration, but not in the tonic and use-dependent block of the
      maximal velocity of action potential upstroke. To elucidate the underlying ionic
      mechanisms, currents through the Na, Ca and K channels were examined by using a
      whole-cell voltage clamp technique on isolated neonatal (< 5 day) and adult (> 3
      months) rabbit cardiac myocytes under various concentrations (0.5, 1.5 and 4.5
      microM) of quinidine. In neonatal and adult myocytes, quinidine caused a
      comparable degree of dose-dependent effects on Na currents including decrease in
      peak Na currents, left-shift of steady-state availability curve and slowing of
      the recovery from inactivation. However, the inwardly rectifier K current and the
      transient outward current were suppressed to a greater extent in the neonatal
      myocytes than in the adult (P = 0.0002 and 0.02, respectively). On the contrary,
      the magnitude of decrease in peak Ca currents after quinidine treatment was much
      smaller in the neonatal myocytes than in the adult (P = 0.01). These findings
      indicate that age-related ionic channel-block by quinidine is complex; and shows
      major differences in the Ca and K currents of cardiac myocytes. Accordingly, a
      differential therapeutic potential of quinidine may exist in hearts of different
      ages.

PMID- 7529325
TI  - Intracranial infusion of monoamine-activated alpha 2-macroglobulin decreases
      dopamine concentrations within the rat caudate putamen.
AB  - Monoamine-activated alpha 2-macroglobulin (alpha 2M) has been shown to inhibit
      choline acetyltransferase in basal forebrain neurons as well as neurotrophin
      dependent neuronal functions. The objective of this study was to determine
      whether monoamine-activated alpha 2M can affect the caudate putamen (CP)
      dopaminergic system in vivo. Male rats received intracranial infusions of
      methylamine-activated alpha 2M (0.6 nmole) and contralateral infusions of its
      vehicle, phosphate-buffered saline (PBS). Five days following infusion, the
      animals were killed, the CP dissected into three rostral-caudal segments, and
      assayed for dopamine (DA) using a high-performance liquid chromatography system.
      Within the two rostral CP segments (the approximate site of cannula placement),
      statistically significant (26%) reductions of DA concentrations were obtained on
      the alpha 2M-infused side of the CP with 90-100% of the animals showing
      decreases. At a more distal (caudal) site of the CP, DA concentrations showed
      only an insignificant (12%) reduction. No differences in DA concentrations
      between sides infused with bovine serum albumin versus PBS or from olfactory
      tubercle samples were obtained in these animals. These results demonstrate that
      monoamine-activated alpha 2M is capable of producing significant degeneration of
      the nigrostriatal dopaminergic system in vivo and suggest that this factor may
      play a role in age-related neurodegenerative disorders such as Parkinson's
      disease.

PMID- 7529329
TI  - Stem cell factor binding to retrovirus primer binding site silencers.
AB  - Using modified nuclear lysis and binding conditions, we have examined the binding
      of an embryonal carcinoma (EC) cell factor, binding factor A, to a stem cell
      specific silencer which acts at the DNA level and overlaps the Moloney murine
      leukemia virus (M-MuLV) proline primer binding site (PBS). Following our
      protocol, we found that in vitro binding of factor A correlated with the in vivo
      activity of the M-MuLV silencer. Factor A bound specifically to the wild-type
      silencer element at room temperature and 30 degrees C, but not at 4 degrees C,
      and bound 10-fold better to the full-length silencer than to a minimal silencer
      core element. The factor was enriched in nuclear compared with cytosolic extracts
      and in undifferentiated EC cells compared with differentiated cells in which the
      silencer is nonfunctional. Salt and ion requirements for factor A binding were
      investigated, and partial purification steps indicated the factor to be a heparin
      Sepharose-binding moiety of greater than 100 kDa. To examine possible
      relationships between silencer and PBS activities, sequences representing
      phenylalanine, isoleucine, lysine-1,2, lysine-3, methionine, and tryptophan PBS
      DNA fragments were tested in vivo for stem cell-specific repression of M-MuLV
      expression and in vitro in DNA binding assays. Of these PBS elements, only the
      lysine-1,2 PBS DNA fragment showed consistently high levels of repression.
      Interestingly, the lysine-1,2 PBS DNA fragment also formed a complex with an EC
      cell factor with characteristics similar to those of factor A. However, the two
      factors did not cross-compete in binding studies, suggesting that they may be
      different but related factors. Our results suggest that expression of Mason
      Pfizer monkey virus, visna virus, and spumavirus, which use the lysine-1,2 PBS,
      may be inhibited in undifferentiated stem cells.

PMID- 7529328
TI  - Polymorphism within the herpes simplex virus (HSV) ribonucleotide reductase large
      subunit (ICP6) confers type specificity for recognition by HSV type 1-specific
      cytotoxic T lymphocytes.
AB  - A panel of herpes simplex virus type 1 (HSV-1)-specific, CD8+, major
      histocompatibility complex class I (H-2Kb)-restricted cytotoxic T-lymphocyte
      (CTL) clones was derived from HSV-1-immunized C57BL/6 (H-2b) mice in order to
      identify the HSV-1 CTL recognition epitope(s) which confers type specificity. HSV
      1 x HSV-2 intertypic recombinants were used to narrow the region encoding
      potential CTL recognition epitopes to within 0.51 to 0.58 map units of the HSV-1
      genome. Using an inhibitor of viral DNA synthesis and an ICP6 deletion mutant,
      the large subunit of ribonucleotide reductase (ICP6, RR1) was identified as a
      target protein for these type-specific CTL. Potential CTL recognition epitopes
      within RR1 were located on the basis of the peptide motif predicted to bind to
      the MHC class I H-2Kb molecule. A peptide corresponding to residues 822 to 829 of
      RR1 was shown to confer susceptibility on H-2Kb-expressing target cells to lysis
      by the type 1-specific CTL. On the basis of a comparison of the HSV-1 RR1 epitope
      (residues 822 to 829) with the homologous sequence of HSV-2 RR1 (residues 828 to
      836) and by the use of amino acid substitutions within synthetic peptides, we
      identified HSV-1 residue 828 as being largely responsible for the type
      specificity exhibited by HSV-1-specific CTL. This HSV-1 RR1 epitope, when
      expressed in recombinant simian virus 40 large T antigen in primary C57BL/6
      cells, was recognized by the HSV-1 RR1-specific CTL clones. These results
      indicate that an early HSV protein with enzymatic activity provides a target for
      HSV-specific CTL and that type specificity is dictated largely by a single amino
      acid.

PMID- 7529327
TI  - Histamine-mediated neuronal death in a rat model of Wernicke's encephalopathy.
AB  - Three experiments were conducted to examine the role of histamine in neuronal
      degeneration in a rat model of Wernicke's encephalopathy induced by an acute bout
      of pyrithiamine-induced thiamine deficiency (PTD). In the first experiment,
      histamine levels in medial thalamus of freely moving PTD rats measured by
      microdialysis were increased (180% of controls) at a prelesion stage of thiamine
      deficiency (treatment day 12) and further elevated 48 hr later (380%) in the same
      animals when necrosis was evident. Histamine levels in dialysates of the
      hippocampus collected simultaneously from the same animals were unchanged at
      either stage of thiamine deficiency. Glutamate levels in microdialysates from the
      same animals were unchanged at the prelesion stage but were significantly
      elevated on the second collection day. In a second experiment, separate groups of
      PTD and pairfed control (CT) rats were infused continuously with either alpha
      fluoromethylhistidine (FMH; 80 mg/day, i.p.), an irreversible inhibitor of
      histamine synthesis, or saline. FMH pretreatment produced a significant
      protection against PTD-induced neuronal loss within the midline-intralaminar and
      anteromedial thalamic nuclei, but had no effect on damage to ventrolateral
      nuclei, anteroventral nucleus, or the mammillary bodies. In a third study,
      histamine (80 micrograms, free base) or vehicle was directly infused into the
      same region of medial thalamus dialyzed in experiment 1. Histamine infusion into
      prelesion PTD but not CT animals resulted in severe neuronal loss and gliosis.
      Infusion of vehicle into the same regions of PTD and CT rats produced a mild
      gliosis restricted to the needle tract with no evidence of neuronal loss. These
      observations together with recent evidence of a histamine enhancement of
      glutamate receptor activation suggest that early histamine release may contribute
      significantly to glutamate-N-methyl-D-aspartate (NMDA)-mediated excitotoxic
      neuronal death in thiamine deficiency-induced Wernicke's encephalopathy.

PMID- 7529330
TI  - Apoptosis-inducing and apoptosis-preventing functions of poliovirus.
AB  - Data showing that an apoptotic reaction (the exit into the cytoplasm and
      nucleolytic internucleosomal degradation of chromosomal DNA, compaction and
      fragmentation of chromatin, cellular shrinkage, and cytoplasmic blebbing)
      developed in a subline of HeLa-S3 cells upon nonpermissive poliovirus infection
      with either a guanidine-sensitive poliovirus in the presence of guanidine, a
      guanidine-dependent mutant in the absence of guanidine, or certain temperature
      sensitive mutants at a restrictive temperature are presented. Essentially, no
      apoptotic reaction occurred upon permissive infection of these cells. Both
      permissive and nonpermissive infections resulted in the inhibition of host
      protein synthesis. Actinomycin D or cycloheximide also elicited a rapid apoptotic
      reaction in uninfected cells. However, preinfection or coinfection with
      poliovirus prevented the apoptotic response to the addition of actinomycin D, and
      preinfection blocked cycloheximide-induced apoptosis as well. These data fit a
      model in which the cells used are prepared to develop apoptosis, with their
      viability due to the presence of certain short-lived mRNA and protein species.
      Poliovirus infection turns on two oppositely directed sets of reactions. On the
      one hand, the balance is driven toward apoptosis, probably via the shutoff of
      host macromolecular synthesis. On the other hand, viral protein exhibits
      antiapoptotic activity, thereby preventing premature cell death. To our
      knowledge, this is the first description of an antiapoptotic function for an RNA
      virus.

PMID- 7529332
TI  - Analysis of the posttranslational modifications of the influenza virus M2
      protein.
AB  - The sites of posttranslational modifications of the influenza A virus M2 protein
      were examined, and the effect of these modifications on the M2 protein ion
      channel activity was analyzed. Cysteine residues 17 and 19 in the M2 protein
      ectodomain form disulfide bonds. The cytoplasmic tail is posttranslationally
      modified by palmitoylation, and mutagenic studies support the view that cysteine
      residue 50 is the site for fatty acylation. In addition, the cytoplasmic tail of
      the M2 protein was found to be posttranslationally modified by the addition of
      phosphate to specific serine residues. Site-directed mutagenesis of serine
      residues in the M2 protein cytoplasmic tail, combined with phosphoamino acid
      analysis, indicated that serine residue 64 is the predominant site for
      phosphorylation but that serine residues 82, 89, and 93 were also phosphorylated
      but to much lesser extents. Disulfide-bond formation, palmitoylation, and
      phosphorylation occurred on M2 protein expressed in mammalian cells infected with
      influenza virus, in mammalian cells in which the M2 protein was expressed from
      DNA expression vectors, and when the M2 protein was expressed in oocytes of
      Xenopus laevis. The membrane currents of oocytes of Xenopus laevis expressing
      wild-type and site-specifically altered forms of the M2 protein, to ablate
      posttranslational modifications, indicated that none of the posttranslational
      modifications significantly affected the ion channel activity of the M2 protein
      in oocytes. Therefore, these data do not indicate a functional role for
      posttranslational modifications of the M2 protein in its ion channel activity.

PMID- 7529331
TI  - Intracellular cleavage and ligation of hepatitis delta virus genomic RNA:
      regulation of ribozyme activity by cis-acting sequences and host factors.
AB  - During replication, a ribozyme within the genomic RNA of hepatitis delta virus
      cleaves multimeric precursors to release a unit-length linear intermediate.
      Intramolecular ligation of this intermediate produces the circular genomic RNA.
      Although one copy of the ribozyme is reconstituted by such ligation, it does not
      subsequently cleave and destroy the circular conformation. We have identified cis
      acting attenuator sequences that prevent self-cleavage of the circular product by
      base pairing with and inactivating the ribozyme. Furthermore, we have shown that
      during the initial processing of the multimeric precursor RNA, host-specific
      factors activate the ribozyme by preventing its association with the attenuator
      sequences. Thus, we demonstrate a novel switching mechanism that regulates
      ribozyme activity inside the cell.

PMID- 7529333
TI  - Expression of cyclin D2 in Epstein-Barr virus-positive Burkitt's lymphoma cell
      lines is related to methylation status of the gene.
AB  - The cyclin D2 gene is not expressed in resting primary B lymphocytes or in group
      I Burkitt's lymphoma (BL) cell lines that retain the characteristics of authentic
      BL cells. Expression of cyclin D2 is induced in primary B lymphocytes following
      infection with Epstein-Barr virus (EBV) or transfection of the EBV genes EBNA-LP
      and EBNA-2. However, attempts to induce cyclin D2 expression in BL cell lines by
      the enforced expression of EBV genes were unsuccessful. Since the demethylation
      agent 5-azacytidine has been shown to modulate viral gene expression in BL cells,
      we explored the possibility that methylation plays a significant role in the
      control of cyclin D2 expression. We show that 5-azacytidine treatment of the Mutu
      CI 179 BL cell line led to expression of cyclin D2 RNA and that expression
      correlated with differences in the methylation status of a CCGG restriction
      enzyme site near the transcription initiation region of the cyclin D2 gene. Thus,
      methylation appears to play a direct role in the regulation of the cyclin D2
      locus in BL.

PMID- 7529334
TI  - Retroviral recombination can lead to linkage of reverse transcriptase mutations
      that confer increased zidovudine resistance.
AB  - Genetic recombination between viral genomes has been shown to contribute to the
      generation of genetic diversity during retrovirus infections. The role of
      recombination in the development of human immunodeficiency virus type 1 (HIV-1)
      zidovudine resistance was investigated as a possible cause of the formation of
      the linked Leu-41/Tyr-215 resistance genotype. Zidovudine resistance is conferred
      by the presence of subsets of four or five amino acid substitutions in the HIV-1
      reverse transcriptase. Zidovudine therapy of asymptomatic HIV-1-infected
      individuals results in the selection of drug-resistant variants that posses
      defined combinations of the five zidovudine resistance mutations. The linked Leu
      41/Tyr-215 resistance genotype appears central to the continued development of
      high-level zidovudine resistance. By using genetically tagged mutant viruses, it
      was possible readily to select recombinant viruses from mixed infections of Leu
      41 and Tyr-215 single mutants in the presence of zidovudine drup pressure. After
      three passages of a mixed infection in the presence of drug, 38% of clones
      screened were recombinant double mutants. In the absence of zidovudine selection,
      little change in the mixed virus populations was noted. No evidence of de novo
      generation of mutations at codons 41 and 215 was seen during any in vitro
      passage. This provides the first example of the role of retroviral recombination
      in the development of HIV-1 variants with increased drug resistance.

PMID- 7529335
TI  - Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins
      induced by an acidic pH.
AB  - The flavivirus envelope protein E undergoes irreversible conformational changes
      at a mildly acidic pH which are believed to be necessary for membrane fusion in
      endosomes. In this study we used a combination of chemical cross-linking and
      sedimentation analysis to show that the envelope proteins of the flavivirus tick
      borne encephalitis virus also change their oligomeric structure when exposed to a
      mildly acidic environment. Under neutral or slightly alkaline conditions, protein
      E on the surface of native virions exists as a homodimer which can be isolated by
      solubilization with the nonionic detergent Triton X-100. Solubilization with the
      same detergent after pretreatment at an acidic pH, however, yielded homotrimers
      rather than homodimers, suggesting that exposure to an acidic pH had induced a
      simultaneous weakening of dimeric contacts and a strengthening of trimeric ones.
      The pH threshold for the dimer-to-trimer transition was found to be 6.5. Because
      the pH dependence of this transition parallels that of previously observed
      changes in the conformation and hydrophobicity of protein E and that of virus
      induced membrane fusion, it appears likely that the mechanism of fusion with
      endosomal membranes involves a specific rearrangement of the proteins in the
      viral envelope. Immature virions in which protein E is associated with the
      uncleaved precursor (prM) of the membrane protein M did not undergo a low-pH
      induced rearrangement. This is consistent with a protective role of protein prM
      for protein E during intracellular transport of immature virions through acidic
      compartments of the trans-Golgi network.

PMID- 7529336
TI  - Gamma interferon-induced, nitric oxide-mediated inhibition of vaccinia virus
      replication.
AB  - Gamma interferon (IFN-gamma)-induced nitric oxide synthase (iNOS) and nitric
      oxide (NO) production in the murine macrophage-like RAW 264.7 cells were
      previously shown to inhibit the replication of the poxviruses vaccinia virus (VV)
      and ectromelia virus and herpes simplex virus type 1. In the current study, we
      performed biochemical analyses to determine the stage in the viral life cycle
      blocked by IFN-gamma-induced NO. Antibodies specific for temporally expressed
      viral proteins, a VV-specific DNA probe, and transmission electron microscopy
      were used to show that the cytokine-induced NO inhibited late protein synthesis,
      DNA replication, and virus particle formation but not expression of the early
      proteins analyzed. Essentially similar results were obtained with hydroxyurea and
      cytosine arabinoside, inhibitors of DNA replication. Enzymatically active iNOS
      was detected in the lysates of IFN-gamma-treated but not in untreated RAW 264.7
      cells. The IFN-gamma-treated RAW 264.7 cells which express iNOS not only were
      resistant to productive infection but also efficiently blocked the replication of
      VV in infected bystander cells of epithelial origin. This inhibition was arginine
      dependent, correlated with nitric production in cultures, and was reversible by
      the NOS inhibitor N omega-monomethyl-L-arginine.

PMID- 7529338
TI  - Expression of the c-kit proto-oncogene and its ligand stem cell factor (SCF) in
      normal and malignant human testicular tissue.
AB  - Recent findings suggest an important role of the proto-oncogene c-kit, a surface
      membrane receptor of the tyrosine kinase family, and its ligand stem cell factor
      (SCF) in normal spermatogenesis and possibly in the pathogenesis of certain
      testicular germ cell tumors. To further investigate this potential role, the
      expression of c-kit and SCF was studied in normal and malignant human testicular
      tissue specimens at the mRNA and protein level by Northern blot analysis and
      immunohistochemistry, respectively. The detection of the c-kit receptor in normal
      human germ cells and its natural ligand SCF in Sertoli cells suggests the
      presence of a local trophic regulatory system that may be active in human
      spermatogenesis. Additionally, c-kit expression was detected in the seminoma but
      not in the nonseminoma subtype of human testicular germ cell tumors (GCT). Stem
      cell factor was not expressed at the mRNA level in tissue from either subtype of
      GCT as determined by Northern blot analysis; however, the protein was detected
      immunohistochemically in the cytoplasm of rare tumor cells.

PMID- 7529339
TI  - Coexistence of nitric oxide synthase, tyrosine hydroxylase and vasoactive
      intestinal polypeptide in human penile tissue--a triple histochemical and
      immunohistochemical study.
AB  - Recently, nitric oxide (NO) has been believed to act as a neuronal messenger to
      mediate penile erection. In the present study using human penile tissue, we
      investigated the coexistence of neuronal NO synthase (NOS), tyrosine hydroxylase
      (TH) and vasoactive intestinal polypeptide (VIP) by a triple staining method
      using NADPH diaphorase (ND) staining, a specific histochemical marker of neuronal
      NOS, and immunohistochemical staining for TH and VIP. Numerous ND-positive nerve
      fibers and TH-containing fibers were seen in axon bundles, but their
      distributions were different. Only a few axons in the bundles showed VIP
      immunoreactivity. Abundant fine varicose nerve terminals innervating cavernous
      smooth muscles and deep and helicine arteries were observed. The proportion of
      fibers showing TH-immunoreactivity in ND-positive terminals in the cavernous
      space was about 25%, and that of VIP was about 40%. Vasoactive intestinal
      polypeptide may act as a coworker in these fibers both in cavernous trabeculae
      and around arteries, as about 40% of NOS-containing fibers also showed VIP
      immunoreactivity. The physiological significance of the colocalization of TH and
      NOS is unclear, and further studies are required to know the physiological
      significance of the colocalization of NOS and other neurotransmitters in penile
      tissue.

PMID- 7529337
TI  - Identification of nuclear and nucleolar localization signals in the herpes
      simplex virus regulatory protein ICP27.
AB  - Previous work has shown that the herpes simplex virus type 1 (HSV-1) regulatory
      protein ICP27 localizes to the cell nucleus and that certain mutant ICP27
      polypeptides localize preferentially in nucleoli. To map the signals in ICP27
      which mediate its nuclear localization, we identified the portions of ICP27 which
      can direct a cytoplasmic protein, pyruvate kinase (PK), to nuclei. Our results
      demonstrate that ICP27 contains multiple nuclear localization signals (NLSs) that
      function with differing efficiencies. First, ICP27 possesses a strong NLS,
      mapping to residues 110 to 137, which bears similarity to the bipartite NLSs
      found in Xenopus laevis nucleoplasmin and other proteins. Second, ICP27 possesses
      one or more weak NLSs which map to a carboxyl-terminal portion of the protein
      between residues 140 and 512. Our PK-targeting experiments also demonstrate that
      ICP27 contains a relatively short sequence, mapping to residues 110 to 152, that
      can function as a nucleolar localization signal (NuLS). This signal includes
      ICP27's strong NLS as well as 15 contiguous residues which consist entirely of
      arginine and glycine. This latter sequence is very similar to an RGG box, a
      putative RNA-binding motif found in a number of cellular proteins which are
      involved in nuclear RNA processing. To confirm the results of the PK-targeting
      experiments, we mutated the ICP27 gene by deleting sequences encoding either the
      strong NLS or the RGG box. Deletion of the strong NLS (residues 109 to 138)
      resulted in an ICP27 molecule that was only partially defective for nuclear
      localization, while deletion of the RGG box (residues 139 to 153) resulted in a
      molecule that was nuclear localized but excluded from nucleoli. Recombinant HSV
      1s bearing either of these deletions were unable to replicate efficiently in Vero
      cells, suggesting that ICP27's strong NLS and RGG box carry out important in vivo
      functions.

PMID- 7529342
TI  - New information about prostate-specific antigen and the paradoxes of prostate
      cancer.

PMID- 7529340
TI  - Health system reform: will controlling cost require rationing services?

PMID- 7529341
TI  - A prospective evaluation of plasma prostate-specific antigen for detection of
      prostatic cancer.
AB  - OBJECTIVE: To evaluate the validity of prostate-specific antigen (PSA) in
      identifying men who subsequently were or were not clinically diagnosed with
      prostate cancer, assess optimal test cutoff, measure lead time, and estimate
      relative risks (RRs) associated with discrete PSA levels. DESIGNS: Nested case
      control study of men providing plasma samples before a 10-year follow-up.
      SETTING: The Physicians' Health Study, an ongoing randomized trial that enrolled
      22,071 men aged 40 to 84 years in 1982. PARTICIPANTS: A total of 366 men (cases)
      diagnosed with prostate cancer and 1098 men (three controls per case), matched by
      age, randomly selected from all cohort members at risk at the time of case
      diagnosis. MAIN OUTCOME MEASURES: Sensitivity and specificity for each year of
      follow-up and for aggressive and nonaggressive cancers separately. RESULTS: At a
      cutoff of 4.0 ng/mL, sensitivity for the entire 10-year follow-up was 46% for
      total cases. Sensitivities for detection of total, aggressive, and nonaggressive
      cancers occurring in the first 4 years were 73%, 87%, and 53%. Overall,
      specificity was 91% and changed little by year of follow-up. Optimal validity was
      achieved at a cutoff of 3.3 ng/mL. Estimated mean lead time for all cancers was
      5.5 years. Only 40% of cancers detected more than 5 years from baseline were
      nonaggressive. Compared with men with PSA levels less than 1.0 ng/mL, those with
      PSA levels between 2.0 and 3.0 ng/mL had an RR of 5.5 (95% confidence interval,
      3.7 to 9.2). CONCLUSIONS: A single PSA measurement had a relatively high
      sensitivity and specificity for detection of prostate cancers that arose within 4
      years. Prostate-specific antigen values less than the usual cutoff were
      associated with substantial increases in risk compared with the lowest levels.
      Final evaluation of PSA screening must also consider cost and the ability of
      current treatments to improve the prognosis of screen-detected cases.

PMID- 7529343
TI  - Indomethacin and symptomatic relief of benign prostatic hyperplasia.

PMID- 7529344
TI  - [Plasma N-methylhistamine levels following intravenous administration of
      pipecuronium in man].
AB  - The half life of released plasma histamine (HA) is short but N-methylhistamine (N
      MHA) which is a metabolite of HA has a longer life. Measuring both HA and N-MHA,
      it is possible to know the release of HA in the plasma. The purpose of this study
      was to ascertain the release of HA by pipecuronium (PPB) by measuring both HA and
      N-MHA in the plasma. Ten patients received 0.04 mg.kg-1 and other 10 patients
      received 0.08 mg.kg-1 of intravenous PPB. Plasma levels of HA and N-MHA were
      measured 1 minute before and 1, 3, 5 and 10 minutes after the administration of
      PPB. Release of plasma HA and N-MHA was not observed following administration of
      PPB. We concluded that PPB does not cause the release of histamine because there
      is no increase of the metabolite, N-MHA, of HA, and PPB can be used safely for
      patients with allergy.

PMID- 7529345
TI  - [Anaphylactic reaction to aprotinin following topical use of biological tissue
      sealant].
AB  - Biological tissue sealant is used for facilitation of intra-operative hemostasis.
      It is composed of cryoprecipitated fibrinogen, bovine-thrombin and bovine
      aprotinin. In this report, we describe a 38-yr-old woman in whom severe
      anaphylactic shock occurred immediately after the topical use of biological
      tissue sealant on the completion of modified radical mastectomy. The patient's
      past history and pre-operative laboratory values were unremarkable except for
      mild nasal allergy. Postoperative prick tests for bovine-serum, bovine-thrombin
      and bovine-aprotinin were positive. Total IgE level was normal. By the
      radioallergosolbent tests (RAST), specific IgE antibodies for aprotinin were
      elevated to the class 2 level. Drug induced lymphocyte stimulation tests (DLST)
      were negative. These indicated that the case was an aprotinin-induced anaphylaxis
      during general anaesthesia. The level of CH50, C4, C1q and C5 decreased in the
      serum sample immediately after the shock, but C3 was unchanged. It was considered
      to be a direct degradation of the complement by the proteolytic enzymes.
      Biological tissue sealant should be used cautiously bearing in mind the
      possibility of anaphylactic complication.

PMID- 7529346
TI  - Effect of celite and kaolin on activated clotting time in the presence of
      aprotinin: activated clotting time is reduced by binding of aprotinin to kaolin.

PMID- 7529347
TI  - Neointima formation is promoted by surgical preparation and inhibited by cyclic
      nucleotides in human saphenous vein organ cultures.
AB  - Intimal thickening is an important cause of late coronary vein graft occlusion,
      which no variation of surgical technique or pharmacologic intervention has been
      shown to reduce. We used a recently developed quantitative organ culture of human
      saphenous vein to investigate whether surgical preparative injury promotes
      neointima formation. We also investigated the effects on neointima formation of
      the lipid-soluble cyclic nucleotide analogs, 8-Br-cyclic adenosine monophosphate
      and 8-Br-cyclic guanosine monophosphate, and the phosphodiesterase inhibitor,
      isobutylmethylxanthine. These agents are pharmacologic mimetics of endothelium
      derived prostacyclin and nitric oxide, which elevate vascular smooth muscle
      cyclic adenosine monophosphate and cyclic guanosine monophosphate concentrations,
      respectively, and may normally suppress neointima formation. Surgical preparation
      was found to promote intimal thickening and neointimal smooth muscle cell
      proliferation by 42% and 48%, respectively. 8-Br-cyclic adenosine monophosphate,
      8-Br-cyclic guanosine monophosphate, or isobutylmethylxanthine (which elevated
      endogenous cyclic adenosine monophosphate concentrations) inhibited intimal
      thickening by 80%, 40%, and 72%, respectively, at a concentration of 0.1 mmol/L.
      The results imply that surgical techniques that avoid preparative injury and
      vasodilator drugs that act by elevating cyclic adenosine monophosphate or cyclic
      guanosine monophosphate concentrations may reduce neointima formation in vein
      grafts.

PMID- 7529348
TI  - Effects of L-arginine and L-nitro-arginine methyl ester on recovery of neonatal
      lamb hearts after cold ischemia. Evidence for an important role of endothelial
      production of nitric oxide.
AB  - Myocardial ischemia and reperfusion results in both ventricular and endothelial
      dysfunction. We have found that the endothelial defect is a reduced vasodilator
      response to an intraarterial infusion of acetylcholine that is likely due to
      reduced nitric oxide release, and we have hypothesized that reduced endothelial
      nitric oxide production contributes to postischemic cardiac dysfunction. However,
      others report that nitric oxide is deleterious after ischemia. We therefore
      examined the effects of infusions of L-arginine (3 mmol/L), a precursor of nitric
      oxide, D-arginine (3 mmol/L), an inactive stereoisomer of L-arginine, L-nitro
      arginine methyl ester (1 mmol/L); a competitive inhibitor of nitric oxide
      synthase, and L-nitro-arginine methyl ester (1 mmol/L) plus L-arginine (3 mmol/L)
      versus controls in isolated blood-perfused neonatal lamb hearts having 2 hours of
      cold cardioplegic ischemia. L-nitro-arginine methyl ester was given before
      reperfusion, and L-arginine and D-arginine were infused for the first 20 minutes
      of postischemic reperfusion. At 30 minutes of reperfusion, by comparison with the
      control group, the L-arginine group showed significantly better recovery (p <
      0.05) of left ventricular systolic function (maximum developed pressure,
      developed pressure at V10 [balloon volume to produce an end-diastolic pressure of
      10 mm Hg during baseline measurement], positive maximum dP/dt, and dP/dt at V10),
      diastolic function (negative maximum dP/dt), coronary blood flow, and endothelial
      function assessed by the coronary vascular resistance response to acetylcholine.
      The L-nitro-arginine methyl ester hearts showed a significantly poorer recovery
      (p < 0.05) in left ventricular function, coronary blood flow, and endothelial
      function than the control group. These effects of L-nitro-arginine methyl ester
      were reversed to equal control values by adding a 3 mmol/L concentration of L
      arginine to L-nitro-arginine methyl ester. There were no significant differences
      in the recovery of any variables between the D-arginine and control groups. These
      results point to an important salutary role for the endothelial production of
      nitric oxide in cardiac recovery after hypothermic ischemia in neonatal lamb
      hearts. The mechanism of these beneficial effects of L-arginine after ischemia
      and reperfusion is likely due to enhancement of the endothelial production of
      nitric oxide.

PMID- 7529349
TI  - A simplified technique for histologic analysis of central nervous system tissues
      using glycol-methacrylate plastic coupled with pre-embedding immunocytochemistry.
AB  - Paraffin and some plastic embedding techniques will destroy many antigens
      routinely detected by immunocytochemistry performed on frozen tissue sections.
      However, morphologic quality is compromised to varying extents in frozen tissue,
      even with the use of cryoprotection. We report a simple glycol-methacrylate (GMA)
      embedding technique using vibratome-sectioned mouse brain reacted for tyrosine
      hydroxylase (TH) immunoreactivity before plastic embedding. In this study we used
      a short (4 h) simple, GMA embedding procedure which subsequently provided 1.5-5.0
      microns sections yielding morphologic details superior to frozen or paraffin
      sections. Prior to embedding we used a peroxidase-antiperoxidase (PAP) reaction
      with the 3,3'diaminobenzidine tetrahydrochloride (DAB) chromogen visualizing TH.
      Several different counterstains were used, demonstrating the versatility of this
      embedding procedure.

PMID- 7529350
TI  - Multiple forms of PSA in serum and clinical significance of results.

PMID- 7529351
TI  - Evolution of the ATP-binding-cassette transmembrane transporters of vertebrates.
AB  - The ATP-binding-cassette transmembrane transporters (ABC transporters) known from
      vertebrates belong to four major subfamilies: (1) the P-glycoproteins (Pgp); (2)
      the cystic fibrosis transmembrane conductance regulators (CFTR); (3) the Tap
      proteins encoded with the major histocompatibility complex of mammals; and (4)
      the peroxisomal membrane proteins. Both Pgp and CFTR have a structure suggesting
      a past internal gene duplication; a phylogenetic analysis indicated that these
      duplications occurred independently, while an independent tandem gene duplication
      occurred in the case of the Tap family. Both the Pgp and Tap proteins show
      evidence of relationship to bacterial ABC transporters lacking internal
      duplication, and both are significantly more closely related to the HlyB and MsbA
      families of transporters from purple bacteria than they are to ABC transporters
      from nonpurple bacteria. The simplest hypothesis to explain this observation is
      that eukaryotic Pgp and Tap genes are descended from a mitochondrial gene or
      genes that were subsequently translocated to the nuclear genome. The Pgp genes of
      eukaryotes are characterized by a remarkable degree of convergent evolution
      between the ATP-binding cassettes of their N-terminal and C-terminal halves,
      whereas no such convergence is seen between the two halves of CFTR genes or
      between the duplicated Tap genes. Exon 13 of the CFTR gene, which encodes a
      putative regulatory domain not found in other ABC transporters apart from CFTR,
      showed high levels of both synonymous and nonsynonymous difference in comparisons
      among different mammalian species, suggesting that this region is a mutational
      hot spot.

PMID- 7529352
TI  - Universal barrier to lateral spread of specific genes among microorganisms.
AB  - A genetic circuit to suppress the lateral spread of cloned genes from recombinant
      to indigenous microorganisms in the environment has been developed. It is based
      on the endonucleolytic activity of the bacterial toxin colicin E3, which has a
      distinct target at the 3' end of the 16S ribosomal RNA; this sequence is
      conserved in virtually all prokaryotic and many eukaryotic genera. Cleavage at
      this sequence separates the mRNA binding sites from the remainder of the 16S
      rRNA, thereby inhibiting protein synthesis. While host bacteria carrying the
      genes for both colicin production and colicin immunity are perfectly viable,
      lateral transfer of the E3 gene to non-immune recipients results in killing of
      such recipients. This genetic circuit decreases operational transfer frequencies
      of cloned genes linked to the E3 gene among a variety of bacterial genera by four
      to five orders of magnitude. In combination with transposon cloning vectors, the
      circuit is predicted to reduce the rate of lateral spread of specific genes to
      ecologically insignificant levels. This system therefore represents a useful tool
      both to explore the evolutionary and ecological consequences of experimentally
      reducing lateral gene spread among microorganisms, and to increase the ecological
      predictability of novel recombinant microorganisms.

PMID- 7529353
TI  - Expression of the linear DNA plasmid pRS64 in the plant pathogenic fungus
      Rhizoctonia solani.
AB  - The plant pathogenic isolate RI-64 of anastomosis group 4 of Rhizoctonia solani
      possesses three linear DNA plasmids (pRS64-1, -2, and -3). Unique poly(A)- RNA,
      0.5 kb in length and hybridizable with the pRS64 DNAs was found in mycelial cells
      of the isolate RI-64. The overall homology at the nucleotide level between pRS64
      1, -2, and -3, and the cDNA prepared from the poly(A)- RNA was 100%, 73%, and
      84%, respectively. The open reading frames found in pRS64-1, -2, and -3 (ORF1-1,
      ORF2-1, and ORF3-1) are 68 amino acids long. The amino acids sequence showed no
      significant homology with known proteins. Extracts from Escherichia coli cells
      expressing ORF1-1 contain a specific protein of 7 kDa. Antisera raised against
      the ORF1-1 product obtained from E. coli cells cross-reacted with the specific
      proteins found in the mycelia. The results indicate that the DNA plasmids found
      in R. solani contain a sequence that encodes a specific protein which may be
      involved in determination of plant pathogenicity.

PMID- 7529354
TI  - Role of guanosine tetraphosphate in gene expression and the survival of glucose
      or seryl-tRNA starved cells of Escherichia coli K12.
AB  - The concentration of guanosine 3',5'-bispyrophosphate (ppGpp) increases in
      bacteria in response to amino acid or carbon/energy source starvation. An
      Escherichia coli K12 delta relA delta spoT mutant lacking the ability to
      synthesize ppGpp lost viability at an increased rate during both glucose and
      seryl-tRNA starvation. Also, the deleterious effect of chloramphenicol on starved
      wild-type cells could be overcome by inducing expression of RelA from a plasmid
      carrying the relA gene transcribed from a tac promoter, prior to starvation and
      chloramphenicol treatment. As demonstrated by two dimensional gel
      electrophoresis, this induction of the RelA protein resulted in global
      alterations in gene expression including increased synthesis of some rpoS
      dependent proteins. The delta relA delta spoT mutant maintained high expression
      of several ribosomal proteins during starvation and appeared to exhibit
      significantly decreased translational fidelity, as demonstrated by an unusual
      heterogeneity in the isoelectric point of several proteins and the failure to
      express higher molecular weight proteins during starvation. Moreover, both rpoS
      dependent and independent genes failed to exhibit increased expression in the
      mutant. It is suggested that the deleterious effects on the cells of the relA,
      spoT deletions are not due solely to the inability of these cells to induce the
      sigma factor sigma s, but also to deficiencies in translational fidelity and
      failure to exert classical stringent regulation.

PMID- 7529355
TI  - The genetic toxicology of ethylenethiourea: a case study concerning the
      evaluation of a chemical's genotoxic potential.
AB  - Ethylenethiourea (ETU) is a metabolite, environmental degradation product and
      minor technical impurity of the ethylenebisdithiocarbamate (EBDC) class of
      fungicides. The genetic toxicology of ETU is important given that ETU causes
      thyroid tumors in rodents and liver tumors in mice. Although it is clear that ETU
      induces thyroid tumors via a non-genotoxic, threshold mechanism, the role ETU
      plays in inducing mouse liver tumors remains to be fully elucidated. Recently,
      Dearfield (Mutation Res., 317, 111-132, 1994) reviewed the genetic toxicology of
      ETU, and concluded that, although ETU is not a potent genotoxic agent, it is
      weakly genotoxic. This view stands in contrast to reports from several
      independent authorities that have generally concurred that ETU is not a mammalian
      genotoxin (IARC, 1987; MAFF, 1990; NTP, 1992; FAO/WHO, 1994). These conflicting
      reports highlight a generic problem in genotoxicity safety assessment: although
      individual test results typically yield either a positive or negative response,
      the overall evaluation of an extensive battery of tests for a particular chemical
      rarely yields an unambiguous conclusion. Recently, Mendelsohn et al. (Mutation
      Res., 266, 43-60, 1992) showed that the response of a chemical to a battery of
      genotoxicity tests is not a dichotomous (i.e., either positive or negative)
      property, but rather, appears to be a continuous property that ranges from
      strongly negative to strongly positive. We have used these data, together with a
      four-step weight of the evidence procedure, to evaluate ETU. Our analysis
      indicates that ETU is not genotoxic in mammalian systems and suggests that ETU
      likely induces mouse liver tumors by a non-genotoxic mechanism.

PMID- 7529356
TI  - Phenolphthalein: induction of micronucleated erythrocytes in mice.
AB  - Phenolphthalein was tested for the induction of micronucleated erythrocytes in
      mice. Results of an initial investigation revealed significant, dose-related
      increases in micronucleated polychromatic erythrocytes (MN-PCE) and
      normochromatic erythrocytes (MN-NCE) in peripheral blood samples of male and
      female mice exposed to 0.6% to 5% phenolphthalein (approximately 1100 to 10,000
      mg/kg/day) in feed for 90 days (Dietz et al., 1992). Results from a second long
      term feed study with Swiss CD-1 mice confirmed this effect. However,
      administration of comparable doses of phenolphthalein by corn oil gavage on two
      consecutive days gave negative results in a mouse bone marrow micronucleus test.
      Subsequent tests were performed to clarify the conflicting results seen in the
      chronic exposure, dosed-feed, peripheral blood studies and the acute, corn oil
      gavage, bone marrow studies. Phenolphthalein was administered to male B6C3F1 mice
      in feed (3%) for 14 days. Peripheral blood samples taken at 4, 7, and 14 days all
      showed significant increases in micronucleated PCE; bone marrow samples taken on
      days 7 and 14 also were clearly positive for micronucleus induction. Therefore,
      comparable results were obtainable from both bone marrow and peripheral blood
      analyses. Because of the negative results in the two-exposure gavage test,
      additional tests were then designed to investigate the effects of bolus vs
      continuous dosing, feeding vs gavage administration, and corn oil vs feed as a
      carrier for phenolphthalein. Results of these tests indicated that the rate of
      exposure to phenolphthalein affects the frequency of induced MN-PCE and that
      micronucleated erythrocytes can be induced by phenolphthalein either by feeding
      or by corn oil gavage administration. In all the acute exposure studies,
      relatively high doses of phenolphthalein (2000-6000 mg/kg/day for at least 2
      days) were required to induce micronuclei. The positive results obtained with
      phenolphthalein in vivo were consistent with the results of an in vitro
      chromosomal aberration test in Chinese hamster ovary cells, where dose-related
      increases in aberrations were noted only in cells treated in the presence of
      induced rat liver S9.

PMID- 7529357
TI  - Genotoxicity testing of five compounds in three Drosophila short-term somatic
      assays.
AB  - To provide further background data for the somatic mutation and/or recombination
      tests in Drosophila melanogaster, we have evaluated the response in 3 assays
      (zeste-white, white-ivory and wing spot) of 5 chemicals classified by the U.S.
      National Toxicology Program (NTP) as genotoxic non-carcinogens (or ambiguous).
      The selected compounds were 2-chloromethylpyridine, 1-nitronaphthalene, 4-nitro-o
      phenylenediamine, 3-nitropropionic acid and p-phenylenediamine. Our results show
      that all the compounds tested produce significant increases in the frequency of
      mutant clones, in at least one of the assays, p-phenylenediamine being the
      compound which presents a clearer mutagenic activity, and the wing spot test, the
      assay that detects more genotoxic compounds (4/5).

PMID- 7529358
TI  - Induction of micronuclei by five pyrethroid insecticides in whole-blood and
      isolated human lymphocyte cultures.
AB  - Five pyrethroid insecticides: cypermethrin, deltamethrin, fenpropathrin,
      fenvalerate and permethrin, were tested for their ability to induce micronuclei
      in both whole-blood (WB; three donors) and isolated human lymphocyte (IL, 2
      donors) cultures, by using the cytokinesis-block method with 6 micrograms/ml
      cytochalasin B (Cyt-B). Fenvalerate and permethrin were tested with two different
      concentrations of Cyt-B (3 and 6 micrograms/ml). At the concentration ranges
      tested, all the five pyrethroids induced clear dose dependent cytotoxic effects,
      fenpropathrin being the most toxic. Nuclear division index (NDI) and the newly
      introduced index of cytotoxicity, the cytokinesis block proliferation index
      (CBPI), reflected the dose dependency more accurately than the percentage of
      binucleated cells did. CBPI is similar to NDI except that it estimates the
      average number of cell divisions that the cell population has gone through, and,
      therefore, classifies both trinucleate and tetranucleate cells into the same
      category. Cypermethrin and fenpropathrin slightly increased the number of MN and
      micronucleated cells in WB lymphocyte cultures from two out of the three donors.
      Deltamethrin produced a positive response only in WB cultures of one donor and in
      IL cultures of another donor. Permethrin gave mostly negative results, although
      it increased the MN frequency in WB cultures of one donor when 6 micrograms/ml
      Cyt-B was used. Fenvalerate did not significantly induce MN. With certain
      reservations to the purity and isomer composition of each pesticide, the existing
      information appears to support the idea that pyrethroid insecticides have a weak
      (cypermethrin, deltamethrin and fenpropathrin) or nule (fenvalerate and
      permethrin) genotoxic activity in vitro.

PMID- 7529359
TI  - The gradient plate assay: a modified Ames assay used as a prescreen for the
      identification of bacterial mutagens.
AB  - Bacterial test systems have been used extensively to identify the mutagenic
      potential of new compounds. In particular, the Ames test has gained worldwide
      acceptance and is required by many regulatory agencies to support product
      registration. The gradient plate assay (GPA) is a modification of the Ames test.
      It is used as a high capacity prescreen to detect the mutagenic potential of
      synthetic intermediates, impurities, and research compounds over a concentration
      gradient. Since the development of the GPA, over 4000 compounds have been tested
      in the assay. Selection and use of the GPA in our laboratory is due to many
      factors: reliability; sensitivity; capacity; timeliness of reporting results; and
      establishment of safety standard in the laboratory. In this manuscript, results
      of the GPA method are compared with results from the traditional Ames assay. To
      date, 113 compounds of identical lots have been evaluated in both tests, and in
      all but 3 instances the results are the same. Thus, the GPA is an ideal assay for
      use as a prescreen in determining the ability of a compound to induce bacterial
      mutation.

PMID- 7529361
TI  - Cytogenetic analyses of the in vitro and in vivo responses of murine cells to
      peroxyacetyl nitrate (PAN).
AB  - Peroxyacetyl nitrate (PAN) is one of a class of common air pollutant formed by
      the action of sunlight on volatile organic compounds and nitrogen oxides. PAN has
      been shown to be a bacterial mutagen. To determine if PAN can cause DNA damage in
      mammalian cells, we exposed murine peripheral blood lymphocytes (PBLs) to various
      volumes of PAN in vitro and analyzed the cells for chromosome aberrations (CAs),
      sister chromatid exchanges (SCEs), and DNA damage using the single cell gel (SCG)
      assay. At in vitro concentrations of PAN that were cytotoxic (inhibited cell
      division), an increase in DNA damage was noted in the SCG assay. At lower
      exposure levels that permitted cell division, no increases in SCEs, CAs, or DNA
      damage were evident. For in vivo studies, male mice were exposed nose-only by
      inhalation for 1 h to 0, 15, 39 or 78 ppm PAN, and their lung cells removed and
      cultured for the scoring of SCEs and CAs. In addition, PBLs and lung cells were
      analyzed by the SCG assay. No dose-related effects were found in any of the
      assays. These data indicate that PAN does not appear to be a potent clastogen or
      DNA damaging agent in mammalian cells in vivo or in vitro.

PMID- 7529360
TI  - Clastogenicity of lanthanides: induction of chromosomal aberration in bone marrow
      cells of mice in vivo.
AB  - Clastogenic properties of two lanthanide elements praseodymium (Pr) and neodymium
      (Nd) were evaluated by employing mouse in vivo chromosomal aberrations (CAs)
      assay. Praseodymium oxide (Pr6O11) and neodymium oxide (Nd2O3) administered
      intraperitoneally to Swiss albino mice in vivo induced significant increase in
      the frequency of CAs in bone marrow cells, when compared to negative control. The
      number of CAs/cell and percent aberrant cells increased with an increase in the
      concentration and period of treatment. The effect was maximum when the cells were
      analysed 12 h after treatment, as compared to 6 and 24 h. This is the first
      report on the clastogenicity of these elements in mouse in vivo.

PMID- 7529363
TI  - Effect of Clostridium perfringens-derived wound healing substance as compared
      with epidermal growth factor on the growth and morphological transformation of
      BALB/3T3 A31-1-1 cells.
AB  - Clostridium perfringens-derived wound-healing substance (WHS), having growth
      stimulating activity, was examined to determine its effect on the growth and
      morphological transformation of BALB/3T3 A31-1-1 cells. WHS accelerated the cell
      growth at the exponential growth phase, shortening the doubling time by 8-18%.
      The maximum cell density of the treated cultures was slightly higher than that of
      the control culture, and the cell number decreased in the same way as the control
      cells did. On the other hand, the cells treated with epidermal growth factor
      (EGF) or insulin showed growth rates similar to that of the control cells during
      the exponential growth phase, and after the control cells attained the maximum
      cell number, the number of the treated cells continued to increase gradually for
      more than 4 days and then decreased. Under the experimental conditions of the two
      stage transformation assay, application of WHS at the tumor-initiation or
      promotion stage did not accelerate the formation of transformed foci. Although
      treatment with EGF at the initiation stage induced no enhancement, marked
      enhancement of morphological transformation was observed in the treatment at the
      promotion stage. These results indicate that the mode of action between WHS and
      EGF or insulin is different on the growth-stimulating activity and morphological
      transformation of BALB/3T3 A31-1-1 cells.

PMID- 7529362
TI  - Application of urinary mutagen testing to detect workplace hazardous exposure and
      bladder cancer.
AB  - The objectives of this biochemical epidemiologic case-control study were to
      evaluate urinary mutagen testing for occupational exposure assessment, and for
      possible screening for bladder cancer in the workplace. Thirty-seven patients (19
      bladder cancer cases and 18 controls) completed a questionnaire. Two urine
      samples, i.e. a work sample taken while at work, and a home sample, were
      requested from each patient. Twenty-six patients (17 cases and 9 controls) gave a
      total of 47 24-h urine samples for mutagenicity testing by the Ames test. A
      positive Ames test was found to be associated significantly with current
      occupation with hazardous exposure (odds ratio = 3.7, 95%CI 1.1-12.9), and non
      significantly with bladder cancer (odds ratio = 1.8, 95%CI 0.5-7.1). Our results
      show that the urinary Ames test has the potential of being used as a surveillance
      for current workplace hazardous exposure (sensitivity = 52%, specificity = 77%,
      positive predictive value = 72%, negative predictive value = 59%, positive
      likelihood ratio = 2.3), but not as a screening test for bladder cancer cases
      (sensitivity = 42%, specificity = 71%, positive predictive value = 3%, negative
      predictive value = 98%, positive likelihood ratio = 1.5).

PMID- 7529364
TI  - Geographical variations in mutagenicity of blue rayon extracts of Japanese human
      bile.
AB  - The mutagenicity of human bile was investigated in the Ames test after blue rayon
      treatment. In the present study, 52 and 59 bile samples were collected from the
      high and the low risk population for gallbladder cancer (GBC), respectively. The
      bile mutagenicity was detected only when the blue rayon extracts of bile were
      assayed with Salmonella typhimurium TA98 in the presence of S9 mix. Thirty-two
      (61.5%) of 52 samples obtained from the high risk population were mutagenic. In
      our previous study (Mano et al., 1993), the mutagenicity was observed in 14
      (58.3%) of 24 samples. After combining this data with the results of the present
      study, 46 (60.5%) of 76 samples revealed the mutagenicity. On the other hand, the
      mutagenicity was detected in only 7 (11.9%) of 59 samples collected from the low
      risk population. Therefore, we found a significant geographical difference in the
      bile mutagenicity.

PMID- 7529367
TI  - Acute effects of interstitial hyperthermia on normal monkey brain--magnetic
      resonance imaging appearance and effects on blood-brain barrier.
AB  - The magnitude and time course of histological and neuroradiological changes due
      to interstitial hyperthermia in normal cerebral white matter were investigated in
      eight adult Japanese monkeys. A cooling system enveloping a 2450-MHz microwave
      antenna was inserted stereotactically into the brain under general anesthesia. A
      point located 5 mm away from the surface of the cooling system was used as the
      reference point (RP). Hyperthermia was given to maintain the RP at 43 degrees C
      for 60 minutes. Two animals were sacrificed under general anesthesia following
      the intravenous administration of Evans blue, immediately and 1, 3, and 7 days
      after treatment. After removing the brain, histological changes were
      investigated. Magnetic resonance (MR) imaging was performed at 1, 3, and 7 days
      after treatment. Evans blue extravasation was most prominent in the region heated
      to 43 degrees C or above immediately after treatment. MR imaging showed obvious
      enhancement in the region heated to 43 degrees C or above 1 day after treatment,
      related to the disruption of the blood-brain barrier (BBB) by hyperthermia. Three
      days after treatment, ring-like enhancement with a central low-intensity area was
      seen in the region heated to about 43 degrees C, caused by BBB disruption and
      slight neovascularization. One week after treatment, an enhanced ring was
      observed in the region heated to less then 43 degrees C which surrounded a low
      intensity area. The enhancement seen 1 week after treatment was caused by
      prominent neovascularization. T2-weighted imaging showed a high-intensity area,
      caused by edema, most prominent 3 days after treatment. Thus chemotherapeutic
      agents should be given just before the end of hyperthermia.

PMID- 7529366
TI  - In vivo effects of the Ca2+ entry blocker nilvadipine on brain surface
      microvessels in rats.
AB  - The effects of the Ca2+ entry blocker nilvadipine on the diameter of the brain
      surface microvessels of rats were studied in vivo using intravital fluorescence
      microscopy and a closed cranial window technique under an intracranial pressure
      of 5-7 mmHg. Intravenous Na(+)-fluorescein was used as a blood-brain barrier
      (BBB) and vessel marker. The BBB function, as determined by the barrier marker,
      remained intact during the entire observation period. Nilvadipine (10(-10)-10(
      6)M) and/or vehicle were dissolved in artificial cerebrospinal fluid (CSF).
      Superfusion of the brain surface with artificial CSF with and without vehicle had
      no effect on vessel diameters. Nilvadipine dilated pial arterioles in a dose
      dependent manner. The arterioles were dilated significantly at concentrations of
      > or = 10(-9)M when compared with resting diameters. The diameters of venules
      were not affected by nilvadipine. The results suggest a possible mechanism for
      the nilvadipine-induced increase in the cerebral blood flow under physiological
      conditions.

PMID- 7529368
TI  - In vivo proton magnetic resonance spectroscopy for metabolic changes of human
      brain edema.
AB  - The metabolism of the brain was investigated in eight patients with peritumoral
      edema, six patients with ischemic stroke, and 28 normal controls using proton
      magnetic resonance (MR) spectroscopy. The MR studies were performed using a 1.5-T
      whole-body imaging and spectroscopy system with a 1500-msec repetition time (TR)
      and a 270-msec echo time (TE). The peak areas for N-acetyl-aspartate (NAA),
      choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and
      lactate (Lac) were measured, and the NAA/Cr, Cho/Cr, and Lac/Cr ratios were
      calculated. To quantify and compare the serial spectra, relaxation effects were
      investigated by acquisitions at two different points (TRs or TEs) and by
      monoexponential fitting. The normal NAA/Cr and Cho/Cr ratios were 2.76 and 1.09,
      respectively. Lac could not be identified in normal brains. In ischemic stroke
      and peritumoral edema, significantly increased Lac/Cr and decreased NAA/Cr ratios
      were observed. Resolution of peritumoral edema was associated with normalized
      NAA/Cr ratio and disappearance of Lac. The T1 relaxation times of the metabolites
      were similar in normal brain and peritumoral edema, but the T2 values were
      significantly shortened. Serial measurements of T2 values in two patients with
      peritumoral edema showed gradual normalization corresponding to improvement of
      the edema. To absolutely quantify metabolite concentrations in edema, changes in
      relaxation times should be considered.

PMID- 7529369
TI  - Symptomatic middle cerebral artery stenosis and occlusion: comparison of three
      dimensional time-of-flight magnetic resonance angiography with conventional
      angiography.
AB  - The usefulness of magnetic resonance (MR) angiography using the three-dimensional
      time-of-flight method for the characterization of symptomatic middle cerebral
      artery (MCA) occlusive lesions was evaluated in 10 patients with MCA occlusion
      and 10 with MCA stenosis. All lesions were symptomatic and documented by
      conventional angiography. There was no false-negative MR angiogram that failed to
      demonstrate the MCA occlusive lesion. MR angiography correctly evaluated the
      location of lesions and the difference between stenosis and occlusion. Stenosis
      appeared as a focal signal loss (< 1.0 cm) of the MCA at the site of stenosis,
      and occlusion as a complete signal loss of the MCA distal to the site of
      occlusion. However, MR angiography could not distinguish diffuse stenosis and one
      point stenosis demonstrated by conventional angiography. MR angiography is a
      useful noninvasive diagnostic method for evaluating occlusive lesions of the MCA
      in symptomatic patients.

PMID- 7529371
TI  - Distal posterior cerebral artery aneurysms--three case reports.
AB  - One case of an aneurysm in the P3 segment and two cases of aneurysms in the P4
      segment of the posterior cerebral artery are described. The P3 aneurysm in a 60
      year-old female and a P4 aneurysm in a 63-year-old male were clipped or coated
      via the occipital interhemispheric approach. The other P4 aneurysm in a 73-year
      old female was clipped via a hematoma cavity. The occipital interhemispheric
      approach should be selected for small or large P3 aneurysms and for P4 aneurysms
      associated with slack brain, as brain retraction is minimal and the approach to
      the aneurysm is straightforward.

PMID- 7529370
TI  - Pituitary adenoma invading the skull base--a strategy for skull base surgery.
AB  - A strategy for surgical management, including the approach and preoperative
      evaluation, of pituitary adenoma invading the skull base is described.
      Preoperative evaluation requires a balloon occlusion test of the internal carotid
      artery (ICA) to determine tolerance to occlusion. Failure to tolerate occlusion
      indicates administration of brain protective agents and/or a bypass procedure
      before tumor removal. The transsphenoidal, pterional, orbitofrontomalar, and
      infratemporal fossa approaches are all suitable for various tumor locations. A
      combined orbitofrontomalar and extended frontal approach allows removal of tumor
      with extensive invasion and is suitable for bypass procedures. Preoperative
      evaluation of ICA occlusion can prevent development of hemodynamic stroke. We
      treated five patients with pituitary adenoma invading the skull base, including
      two primary and three recurrent cases. All symptoms improved, but temporary
      oculomotor nerve disturbance occurred in three patients and anosmia in one.
      Reoperations for recurrent pituitary adenomas were effective in reversing the
      symptoms. No hemodynamic stroke was seen postoperatively. These tumors, except
      for drug-responsive cases, are indicated for skull base surgery.

PMID- 7529365
TI  - Viral dynamics in human immunodeficiency virus type 1 infection.
AB  - The dynamics of HIV-1 replication in vivo are largely unknown yet they are
      critical to our understanding of disease pathogenesis. Experimental drugs that
      are potent inhibitors of viral replication can be used to show that the composite
      lifespan of plasma virus and virus-producing cells is remarkably short (half-life
      approximately 2 days). Almost complete replacement of wild-type virus in plasma
      by drug-resistant variants occurs after fourteen days, indicating that HIV-1
      viraemia is sustained primarily by a dynamic process involving continuous rounds
      of de novo virus infection and replication and rapid cell turnover.

PMID- 7529372
TI  - Cerebral bacterial aneurysm and indications for cerebral angiography in infective
      endocarditis.
AB  - Six infective endocarditis patients who developed cerebral bacterial aneurysm
      were reviewed to clarify the indications and timing for cerebral angiography to
      achieve early detection of unruptured aneurysms. All cerebral bacterial aneurysms
      were confirmed either angiographically or at autopsy. All patients were treated
      conservatively. Four patients died due to ruptured aneurysm. Four of the six
      patients showed the signs and symptoms of cerebral and/or systemic embolism,
      followed by rupture or detection of cerebral bacterial aneurysm. Prodromal signs
      and symptoms of embolism in patients with infective endocarditis should be
      considered as indicators for cerebral angiography to detect cerebral bacterial
      aneurysms before rupture.

PMID- 7529373
TI  - Remission of recurrent primary intracranial malignant lymphoma after high-dose
      intra-arterial corticosteroid administration and intra-arterial chemotherapy-
      case report.
AB  - A 39-year-old male presented with rapidly growing recurrent primary intracranial
      malignant lymphoma, manifesting as intractable headache, recent memory
      disturbance, and left hemiparesis during the previous month. He had received
      irradiation and chemotherapy for primary intracranial malignant lymphoma 15
      months before admission. Signs of uncal herniation developed soon after
      admission. High-dose intra-arterial corticosteroid infusion followed by intra
      arterial chemotherapy (etoposide and cisplatin) successfully relieved the
      symptoms of uncal herniation. Magnetic resonance imaging demonstrated a dramatic
      remission in the size of the tumor and associated mass effect. Sequential
      administration of corticosteroid and chemotherapy agents is a possible treatment
      for recurrent malignant lymphoma.

PMID- 7529375
TI  - Cerebellar porencephaly in an adult--case report.
AB  - A 51-year-old female presented with an extremely unusual cerebellar porencephalic
      lesion manifesting as progressive cerebellar signs and cranial nerve pareses. T1
      weighted magnetic resonance imaging demonstrated a low-signal-intensity area in
      the left cerebellar hemisphere suggesting a cavity communicating with the fourth
      ventricle. Histological study showed the wall of the cavity contained nonspecific
      gliosis. A diagnosis of porencephaly was made.

PMID- 7529374
TI  - Maxillary ameloblastoma with intracranial invasion--case report.
AB  - A 79-year-old male presented with recurrent maxillary ameloblastoma with
      intracranial invasion into the left orbit, previously histologically diagnosed as
      benign ameloblastoma. Skull x-ray films and computed tomography showed the
      multicystic mass had destroyed the skull base. The tumor was nearly completely
      removed. However, microscopic examination revealed residual tumor cells around
      the left optic nerve. Histological examination found no malignant transformation
      in the tumor specimen. Aggressive complete removal of maxillary ameloblastoma
      should be attempted even in cases of intracranial invasion.

PMID- 7529376
TI  - Two NK-3 receptor subtypes: demonstration by biological and binding assays.
AB  - The existence of two neurokinin NK-3 receptor subtypes has been suggested on the
      basis of results obtained in binding assays. In the present study, we have
      confirmed the two NK-3 receptor subtypes by using data obtained in both
      biological and binding assays. Experiments have been performed in the rat portal
      vein and in the guinea-pig ileum treated with NK-1 and NK-2 selective
      antagonists, namely CP 96345 and SR 48968. Orders of potency of agonists on the
      rat portal vein are as follows: for neurokinins, NKB > NKA > SP; for tachykinins,
      KAS > ELE > PHY; and for selective agonist: [MePhe7]NKB >> senktide. On the
      guinea-pig ileum, the agonist rank orders of potency are: NKB > SP > NKA, ELE >
      KAS > PHY; and for selective agonist: [MePhe7]NKB = senktide. The apparent
      affinity of antagonists shows differences in both biological and binding assays.
      In fact, on the rat portal vein, SR 48968 is almost inactive (pA2 or IC50
      approximately 4.8), while R-486 [Trp7, beta Ala8]NKA(4-10) shows a pA2 value of
      7.45 and an IC50 of 5.6. An opposite pattern of activity is observed in the
      guinea-pig ileum, where SR 48968 shows a pA2 of 6.05 and an IC50 of 6.7, while R
      486 has a pA2 of 6.1 and an IC50 of < 5.0. These results confirm the existence of
      two NK-3 sites differing pharmacologically. It is proposed to name NK-3A the
      receptor of the guinea-pig ileum and NK-3B the receptor of the rat portal vein.

PMID- 7529377
TI  - Increased numbers of substance P-containing sensory neurons in a rat strain with
      a genetic neurotrophic defect.
AB  - The GH inbred Wistar rat possesses reduced numbers of sympathetic motor neurons.
      In the present study, we report that substance P (SP) concentrations in superior
      cervical ganglion, spinal cord, iris and trachea of GH rats are about two-fold
      those in normal rats, and that SP-containing sensory neuron numbers are elevated
      in GH rats. These data suggest increased perinatal survival of SP neurons in the
      GH strain, due to reduced competition by sympathetic neurons for limited amounts
      of nerve growth factor. By contrast with the situation in iris and trachea, we
      found no difference between GH and normal rats in SP content of ear skin, atrium
      or stomach. This accords with previous findings that only some SP sensory neurons
      are responsive to nerve growth factor.

PMID- 7529378
TI  - Nitric oxide synthase in the pig autonomic nervous system in relation to the
      influence of NG--nitro-L-arginine on sympathetic and parasympathetic vascular
      control in vivo.
AB  - Nitric oxide synthase, the enzyme responsible for the formation of nitric oxide,
      was demonstrated by an indirect immunofluorescence technique to be present in
      both the sympathetic and parasympathetic nervous system of the domestic pig. In
      the sympathetic nervous system, nitric oxide synthase was mainly present in
      preganglionic neurons projecting to postganglionic neurons, some of which
      contained neuropeptide Y in the superior cervical, the coeliac and the lumbar
      ganglia of the sympathetic chain. A minor population of postganglionic
      sympathetic neurons contained nitric oxide synthase, vasoactive intestinal
      polypeptide and peptide histidine isoleucine. In the densely sympathetically
      innervated vascular beds such as the spleen, kidney and skeletal muscle, many
      neuropeptide Y- but no nitric oxide synthase-positive fibres were found. The
      nitric oxide synthase inhibitor NG-nitro-L-arginine reduced cardiac output by 40%
      and caused profound vasoconstriction in a variety of vascular beds. Furthermore,
      no or minor changes in plasma catecholamines, neuropeptide Y or endothelin-1 were
      observed up to 20 min after NG-nitro-L-arginine. Milrinone (a phosphodiesterase
      III inhibitor) prevented this NG-nitro-L-arginine-induced reduction in cardiac
      output, and the regional vasoconstriction was reduced, whereas some elevation of
      the blood pressure was still observed. Sympathetic nerve stimulation, with single
      impulses of 10 Hz for 1 s in the presence of NG-nitro-L-arginine, evoked
      vasoconstrictor responses which were largely in the same range as in control
      conditions. Parasympathetic postganglionic neurons to the submandibular salivary
      gland contained nitric oxide synthase, vasoactive intestinal polypeptide, peptide
      histidine isoleucine and neuropeptide Y. The vasodilatation evoked by
      parasympathetic nerve stimulation (10 Hz for 1 s) in the presence as well as in
      the absence of atropine was, on the other hand, markedly reduced by NG-nitro-L
      arginine administration. Milrinone attenuated the inhibitory effect of NG-nitro-L
      arginine on the parasympathetic vasodilation. In conclusion, nitric oxide
      synthase can be demonstrated in preganglionic sympathetic and postganglionic
      parasympathetic neurons. The main effect of nitric oxide synthase inhibition
      seems to be related to attenuation of basal endothelial nitric oxide production
      and parasympathetic transmission. Inhibition of phosphodiesterase counteracts
      both the haemodynamic and the neuronal effects of NG-nitro-L-arginine.

PMID- 7529379
TI  - Distribution of neuropeptide Y in the developing human spinal cord.
AB  - The distribution of neuropeptide Y at different levels of the spinal cord of 23
      human fetuses aged from 10-41 weeks of gestation was studied using
      immunocytochemical staining. Neuropeptide Y-immunoreactive neurons were
      identified at all levels of the spinal cord examined as early as 10 weeks of
      gestation. These cells were localized in the superficial layers (laminae I and II
      of Rexed) of the dorsal gray matter. As the age of the fetuses increased, their
      cell number increased and the region containing positive neurons extended from
      the superficial to deep layers (laminae III and VI). Immunoreactive fibers
      started to appear in fetuses at 10 weeks of gestation. They were found not only
      in the gray and white matters, but also in the pia mater lining the spinal cord.
      As the fetuses aged, the neuropeptide Y-immunoreactive fibers became mostly
      concentrated in the intermediate zones of the thoracic and sacral segments
      corresponding to the developing autonomic centers. Our results suggest that
      neuropeptide Y may play a role in the early development of the autonomic system.

PMID- 7529380
TI  - Expression of adhesion molecules in poststreptococcal glomerulonephritis.
AB  - Because adhesion properties of leukocytes are important for the influx and
      localization of leukocytes in sites of inflammation, we studied, the expression
      of intercellular adhesion molecule 1 (ICAM-1), lymphocyte-function-associated
      antigen 1 (LFA-1), vascular cell adhesion molecule- 1 (VCAM-1) and CD 11b in 14
      kidney biopsies of PSGN patients, arbitrarily divided into early biopsies (less
      than 15 days after onset of PSGN) and late biopsies (17-90 days). In PSGN,
      intraglomerular ICAM-1 expression was increased in early biopsies (score 3.1 +/-
      SEM 0.2; P < 0.005) and decreased with time; in late biopsies the score (2.0 +/-
      0.2) was similar to that of normal kidney (1.3 +/- 0.3). In the interstitium ICAM
      1 was increased (early PSGN = 836 +/- 56 positive cells/mm2, late = 552 +/- 60.0;
      versus normal = 364 +/- 12.4; P < 0.05). LFA-1 expressing cells in glomeruli were
      also increased in early biopsies (10.0 +/- 2.1 positive cells per glomerular
      cross-section (gcs), versus normal 2.9 +/- 1.4; P < 0.05). In the interstitium,
      LFA-1 positive cells were increased (early PSGN = 221 +/- 79.6 cells/mm2, late
      PSGN = 134.5 +/- 45.1, normal = 21 +/- 8.7; P < 0.05). VCAM-1 in glomeruli and
      interstitium was not increased in PSGN. Our studies demonstrate increased
      expression of adhesion molecules ICAM-1 and LFA-1 in the kidney of PSGN patients,
      and these findings were more pronounced in early biopsies; adhesion molecules are
      probably involved in the inflammatory infiltration of this disease.

PMID- 7529381
TI  - In-vitro effects of cyclosporin A, FK506, 6-mercaptopurine, and prednisolone on
      lymphokine-activated killer cells.
AB  - In transplant recipients, immunosuppressive regimens are deleterious on natural
      killer (NK) and lymphokine-activated killer (LAK) cells, which beyond their well
      known antitumoral activity display many important biological functions. In order
      to find which regimens could preserve NK and LAK functions we tested the
      influence of CsA, FK506, 6-mercaptopurine and prednisolone on HLA-unrestricted
      cytotoxicity during an in-vitro IL-2 activation. For each drug we obtained
      peripheral blood samples from 11 healthy volunteers. Non-adherent PBMC were
      incubated 2 days with either CsA, FK506, 6-mercaptopurine or prednisolone, whose
      concentrations ranged from 0 to 10 micrograms/ml, in order to screen
      infratherapeutic, therapeutic, and supratherapeutic doses. Thereafter, 100 IU of
      IL-2 were added for a further 3-day culture. Before and after the culture, we
      analysed (1) the cell subsets by direct immunofluorescence staining with anti
      CD3/CD16/CD56 antibodies, (2) the LAK activity with the lysis of Daudi cells, (3)
      the cell proliferation with a 24-h incorporation of thymidine. Cyclosporin and
      FK506 did not impair the LAK cytotoxicity nor the number of LAK cells, whereas
      both prednisolone and 6-mercaptopurine decreased the LAK cytotoxicity, the number
      of CD3- CD16+ CD56+ cells, and the thymidine uptake. As a whole, the LAK
      cytotoxicity was correlated with the number of CD3- CD16+ CD56+ cells but not
      with the number of CD3+ CD16- CD56- cells, and it also increased with the
      incorporation of thymidine. This latter was correlated with the number of CD3-
      CD16+ CD56+ cells, but not with the number of CD3+ CD16- CD56- cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7529382
TI  - Lipids and serotonin: a possible link?

PMID- 7529383
TI  - Defective activity of Na+,K(+)-ATPase in peripheral nerve of diabetic rats is
      independent of the axonal transport of the enzyme.
AB  - This study addressed the question as to whether the reduced activity of Na+,K(+)
      ATPase reported to occur in diabetic nerves and to play a crucial role in the
      pathogenesis of diabetic neuropathy could be due to derangements in the axonal
      transport of the enzyme. A micromethod was developed to evaluate the ATPase
      accumulation in individual segments of ligated sciatic nerves from streptozotocin
      induced diabetic rats. The results confirmed a approximately 40% decrease in the
      background activity, but showed that the enzyme was transported at similar rates
      in both anterograde and retrograde directions, suggesting that the decrease in
      its activity does not depend on an altered delivery along the axons.

PMID- 7529384
TI  - The phosphatase inhibitor, okadaic acid, increases peptide release from rat
      sensory neurons in culture.
AB  - We examined the effects of the phosphatase inhibitor, okadaic acid, on substance
      P and calcitonin gene-related peptide release from embryonic rat sensory neurons
      grown in culture. Exposing isolated sensory neurons to 500 or 1000 nM okadaic
      acid for 30 min resulted in a 2- to 5-fold increase in the release of either
      peptide above resting levels and this evoked release was dependent on
      extracellular calcium. Treating sensory neurons with 250 nM okadaic acid did not
      alter resting peptide release, but significantly enhanced peptide release evoked
      by either 50 nM capsaicin, 100 nM bradykinin, or 30 mM KCl. These results suggest
      that enhancing phosphorylation in sensory neurons is an important component in
      augmenting transmitter release.

PMID- 7529386
TI  - An immortalised murine hypothalamic neuronal cell, GT1-7, expresses functional
      histamine H1 receptors.
AB  - Histamine, acting via H1 receptors, dose-dependently stimulated [3H]inositol
      phosphate production in GT1-7 neuronal cells. GT1-7 cells also responded to
      Substance P but not to other neuroactive drugs tested. Acute histamine
      pretreatment desensitised the histamine-induced response, resulting in a
      reduction in the maximal response and a slower time-course of [3H]-inositol
      phosphate production. The desensitisation phenomenon was reversible, with full
      recovery by 2 h.

PMID- 7529385
TI  - Inhibitory effect of okadaic acid on noradrenaline exocytosis from guinea-pig vas
      deferens.
AB  - The effects of okadaic acid (30 microM), a protein phosphatase inhibitor, on
      noradrenaline (NA) release evoked by 70 mM KCl and 100 microM ouabain were
      evaluated in guinea-pig vas deferens. Release of NA evoked by high KCl was
      inhibited by okadaic acid but this inhibition was antagonized by Bay K 8644.
      Furthermore, okadaic acid, like Ca(2+)-channel blockers, reduced NA release by
      ouabain. However, ATP-release induced by alpha,beta-methylene ATP was virtually
      unaffected by okadaic acid or Ca(2+)-free medium. These findings suggest that
      phosphatases may play an important role in Ca(2+)-channel activation and
      consequent NA exocytosis from adrenergic nerves.

PMID- 7529387
TI  - An N-terminal fragment of substance P, substance P(1-7), down-regulates
      neurokinin-1 binding in the mouse spinal cord.
AB  - Injected intrathecally, substance P (SP) down-regulates neurokinin-1 (NK-1)
      binding in the spinal cord and desensitizes rats to the behavioral effect of SP.
      N-terminal fragments of SP, such as SP(1-7), induce antinociception and play a
      role in desensitization to SP in mice. The goal of this study was to assess the
      abilities of N- and C-terminal fragments of SP to down-regulate NK-1 binding.
      Binding of [3H]SP to mouse spinal cord membranes was inhibited by SP, CP-96,345,
      and to a lesser extent by SP(5-11), but not SP(1-7), consistent with these
      binding sites being NK-1 receptors. Injection of SP(5-11) intrathecally did not
      affect the affinity (Kd) or concentration (Bmax) of [3H]SP binding. However,
      injection of 1 nmol of SP(1-7) decreased the Bmax of [3H]SP binding in the spinal
      cord at 6 h after its injection just as this dose of SP decreased the Bmax at 24
      h. These data suggest that the N-terminus of SP is responsible for down
      regulation of NK-1 binding. As SP(5-11) did not down-regulate NK-1 binding,
      activation of NK-1 sites does not appear necessary or sufficient for down
      regulation of SP binding. In contrast, SP(1-7), in spite of its inability to
      interact with NK-1 sites, did down-regulate SP binding, suggesting an indirect
      mechanism dissociated from NK-1 receptors.

PMID- 7529388
TI  - Detection and quantitation of 5-HT1A and 5-HT2A receptor mRNAs in human
      hippocampus using a reverse transcriptase-polymerase chain reaction (RT-PCR)
      technique and their correlation with binding site densities and age.
AB  - The presence and abundance of 5-HT1A and 5-HT2A receptor mRNAs in post mortem
      human hippocampus was investigated using a novel quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) technique using cyclophilin mRNA
      as an internal standard. 5-HT1A and 5-HT2A receptor mRNAs were each co-amplified
      with varying dilutions of cyclophilin primers, and their abundance expressed as a
      ratio of cyclophilin mRNA. Using this technique in combination with quantitative
      autoradiography we have investigated the effect of aging on hippocampal 5-HT1A
      and 5-HT2A receptor mRNA abundance and binding site densities. There was a
      significant negative correlation between hippocampal 5-HT1A receptor binding site
      densities and age and a similar trend for 5-HT1A receptor mRNA abundance. Neither
      5-HT2A receptor binding site densities nor mRNA abundance were affected by age.
      Both 5-HT1A and 5-HT2A receptor binding site densities in individual subjects
      correlated significantly with abundance of their encoding mRNA. This study
      demonstrates that 5-HT1A and 5-HT2A receptor mRNAs can be measured in small
      samples of human brain. Combining studies of mRNA with those directed at binding
      sites will help reveal mechanisms underlying changes in expression of these
      receptors in various neuropsychiatric disorders.

PMID- 7529390
TI  - Use and effectiveness of physical self-care strategies for interstitial cystitis.
AB  - Interstitial cystitis is a painful disease that primarily affects women. It
      involves a chronic bladder inflammation of unknown etiology and unpredictable
      course. There is no consensus about treatment. Women with interstitial cystitis
      report using multiple strategies and interventions to prevent and manage urinary
      urgency, frequency, and suprapubic pain. A survey questionnaire on self-care
      strategies was completed by 138 members of the Interstitial Cystitis Association.
      Subjects indicated how often they used more than 300 self-care strategies and the
      effectiveness of these strategies. This article reports findings from five
      physical subdomains (medications, treatments, hygiene, diet, and body comfort).
      Among those who report actually using the methods the effectiveness ratings for
      many body comfort strategies are comparable to the reported effectiveness of
      medications (including narcotics) for managing mild to moderate symptoms.

PMID- 7529391
TI  - The effect of varying type and volume of sedimenting agents on leukocyte
      harvesting and labelling in sickle cell patients.
AB  - Leukocyte labelling in patients with sickle cell anaemia has been reported as
      difficult if not impossible due to the slow erythrocyte sedimentation rate (ESR)
      in these patients. This study investigated standard sedimentation methods in
      patients with sickle cell disease (n = 16) and compared the results obtained with
      those following changes in the amount and type of sedimenting agent used.
      Labelling with either 111In-oxine or 99Tcm-exametazime was attempted in only five
      patients. Replacement of the commonly used 6% Hetastarch (Hespan) with Dextran or
      Haemaccel did not improve leukocyte harvesting, even when the proportions used of
      these agents were increased. In most cases where standard procedures for
      leukocyte collection did not lead to harvesting of viable samples, it was
      possible to obtain adequate leukocyte labelling in the majority of sickle cell
      patients using a minor modification of standard techniques. In this group of
      patients a ratio of 8 ml of Hespan to 16 ml of blood should be used for cell
      separation. If this fails then donor cells, anti-granulocyte antibody labelling
      or HIG should be considered.

PMID- 7529389
TI  - Bi-directional effects of intrathecal NMDA and substance P on rat dorsal horn
      neuronal responses.
AB  - Intrathecal NMDA (5 ng) facilitated wind-up but not C-fibre evoked responses,
      whereas 50 ng facilitated C-fibre and A delta-fibre evoked responses but not wind
      up of convergent dorsal horn neurones in the halothane anaesthetized rat. Higher
      doses of NMDA and SP (10-500 ng) were without effect. Co-administered SP (10 ng)
      with NMDA (5 ng) facilitated A delta-fibre evoked responses and wind-up.
      Excitatory amino acid and peptide interactions are discussed.

PMID- 7529392
TI  - Immunohistochemical and ultrastructural study of the cornea in Chandler's
      syndrome. Report of a case.
AB  - A corneal specimen obtained by surgery in a 55-year-old woman with Chandler's
      syndrome was studied by light and transmission electron microscopy as well as by
      immunocytochemistry. The pathologic features were abnormalities of the
      endothelially derived cells lining the posterior corneal surface with a fibrous
      material consisting of collagen fibrils, filaments and banded material similar to
      that found in the anterior part of Descemet's membrane observed between the
      endothelial cell layer and Descemet's membrane. The multilayered endothelial cell
      layer in our case was found to be strongly positive for cytokeratins K7 and KL1
      and vimentin and negative for factor-VIII-related antigen, neuron-specific
      enolase, nerve tissue S-100 protein, epithelial membrane antigen, CD 68, actin
      and desmin. This immunohistochemical reaction pattern argues in favor of an
      epithelial origin for cells lining the endothelial cell layer in Chandler's
      syndrome.

PMID- 7529393
TI  - Prevaccination with diluted Freund adjuvant prevents the development of chronic
      pain and transient release of cerebrospinal fluid substance P in adjuvant-induced
      arthritis in rats.
AB  - Parallel time courses of preclinical and behavioural pain-related parameters and
      levels of substance P-like immunoreactivity in plasma (plasma-SPLI) and
      cerebrospinal fluid (CSF-SPLI) were studied in 2 groups of rats injected with an
      arthritogenic solution (concentrated Freund adjuvant) over a 9-week post
      infection (PI) period; 1 group was pretreated with saline (control) and 1
      pretreated with diluted Freund adjuvant (immunized). In control rats all symptoms
      of adjuvant-induced arthritis (AIA) developed while in immunized rats AIA
      symptoms were significantly reduced or did not appear. A significant increase in
      plasma-SPLI was obvious as early as the 2nd week PI and remained at this level in
      both groups of animals until the end of the 9-week PI observation period, but
      with a significantly higher increase in control versus immunized group at all
      stages. In contrast, CSF-SPLI transiently peaked only in the control group at 3
      weeks PI whereas CSF-SPLI values did not differ from one week to another in both
      groups of rats. These results suggest that successive injections of diluted
      Freund adjuvant impairs the development of chronic inflammation and pain in AIA
      in rats, as well as the transient increase in SP release in CSF at 3 weeks PI,
      but not the long-lasting increased SP release in plasma. Since there is a clear
      dissociation between our biochemical and preclinical and behavioral data, this
      study does not provide evidence for the role of substance P as a possible
      biologic marker of chronic pain either in plasma or in CSF.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7529396
TI  - Developmental gene expression in the human fetal pancreas.
AB  - Differential developmental regulation of pancreas-specific genes has not been
      reported for the human fetal pancreas. We have therefore undertaken a systematic,
      quantitative analysis of the transcriptional levels of various genes in the human
      pancreas at different stages of fetal and postnatal development. Using sensitive
      ribonuclease protection assays, in situ hybridization, and the polymerase chain
      reaction, our results indicate the following: 1) Transcriptional levels of
      insulin and amylin remain lower in the fetal than in the adult pancreas, whereas
      glucagon and somatostatin mRNA levels are consistently greater after 14 wk
      gestation than postnatally. These results are in agreement with previous
      immunohistochemical studies of these gene products. 2) The reg gene exhibits a 20
      fold increase in mRNA levels after 16 wk gestation. The gene is expressed
      exclusively in the acinar cells and does not colocalize with insulin. This
      restricted exocrine expression does not indicate a direct role for the reg gene
      in islet development. 3) Glucose transporter 2 and glucokinase mRNA are
      detectable as early as 13 wk gestation and remain low throughout development.
      Glucose transporter 1 reaches adult transcriptional levels by 18 wk gestation.
      The early detection of glucose transporter 2 and glucokinase implies that lack of
      expression of these "glucose sensor" genes does not account for the known
      insensitivity of the fetal beta-cells to glucose.

PMID- 7529395
TI  - Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3:
      quantitative measurements by radioimmunoassay in human fetal serum.
AB  - There is evidence for a role for IGF-I in the endocrine control of human fetal
      growth despite the low serum IGF-I concentrations. The formation in serum of
      binary complexes between IGF-I or -II and either of six IGF binding proteins
      (IGFBP-1 to -6) and, in particular, of long-lived ternary complexes between IGF-I
      or -II, IGFBP-3, and acid-labile subunit is thought to regulate IGF-I
      bioavailability by increasing its serum half-life. The present study assesses the
      bioavailability of circulating IGF-I in 19- to 35-wk gestation human fetuses in
      utero 1) by quantitative RIA measurements of IGF and IGFBP in serum and 2) by
      examining whether serum proteolysis of IGFBP-3 may further increase IGF-I
      bioavailability. Fetal serum concentrations of IGFBP-3, IGF-I, and IGF-II were
      low with marked or only modest increases with gestational age (p < 0.001, p <
      0.005, and p < 0.05, respectively). The mean molar ratio between IGF-I plus -II
      and IGFBP-3 demonstrated a molar excess of IGF (50%) similar to that in
      adolescents but in contrast to the 1:1 molar ratio in adults. The median IGFBP-2
      concentration was 3-fold elevated to a molar concentration similar to that of
      IGFBP-3 (adult serum displays 10-fold higher IGFBP-3 concentrations). The median
      serum IGFBP-1 concentration was not elevated as previously reported in newborns.
      IGFBP-3 protease activity was not increased in fetal serum, in contrast to
      pregnancy serum and amniotic fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529397
TI  - Ion channels in the basolateral membrane of intralobular duct cells of mouse
      mandibular glands.
AB  - We have used single-channel patch-clamp techniques to study the ion channels in
      the basolateral membranes of intralobular duct cells from the mouse mandibular
      gland. In 39% of cell-attached patches, we observed a K+ channel that had an
      inwardly rectifying current/voltage (I/V) relation with a maximum slope
      conductance of 123 +/- 9 pS (n = 12) and a zero current potential of +49.4 +/-
      3.4 mV (n = 5) relative to the resting cell potential. The selectivity sequence
      of this channel, as estimated by zero current potential measurements, was: K+ (1)
      > Rb+ (0.38) > NH4+ (< 0.34), Cs+ (< 0.16) > Na+ (< 0.028). The activity of the
      channel was not affected by changes in membrane potential, nor was it affected by
      changes in the free Ca2+ concentration on the cytosolic side of inside-out
      excised patches in the range 1 nmol/l to 1 mumol/l. In 38% of cell-attached
      patches we observed a second K+ channel type with a maximum slope conductance of
      62 +/- 3 pS (n = 12) and an inwardly rectifying I/V relation. The selectivity
      sequence of this channel was K+ (1) > Rb+ (< 0.5) > NH4+ (< 0.2) > Na+ (< 0.09).
      The activity of this channel type was not affected by changes in membrane
      potential. In 18% of excised patches, we also observed a non-selective cation
      channel that was not demonstrable in cell-attached patches. It had a slope
      conductance of 22 +/- 2 pS (n = 6) and was blocked by the non-selective cation
      channel blocker, flufenamate (10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529394
TI  - Tyrosine kinase activity is necessary for growth factor-stimulated rabbit type II
      pneumocyte proliferation.
AB  - Tyrosine kinases are important in the signal transduction of a number of growth
      factors. As shown previously, transforming growth factor (TGF)-alpha stimulated
      proliferation of type II cells in vitro. The mitogenic effect of TGF-alpha could
      be blocked by the addition of the tyrosine kinase inhibitors genistein or
      tyrphostin. Tyrosine phosphorylation in type II cells exposed to growth factors
      was examined using an antiphosphotyrosine antibody. After addition of TGF-alpha,
      phosphorylation of a tyrosine protein with a molecular mass of 170 kD, presumed
      to be the epidermal growth factor receptor (EGF-R), peaked by 5 min, returning to
      baseline by 30 min. As expected, genistein or tyrphostin decreased the TGF-alpha
      induced phosphorylation of the EGF-R. Addition of TGF-beta resulted in no newly
      phosphorylated tyrosine proteins. TGF-beta decreased the TGF-alpha-induced
      phosphorylation of the EGF-R. Previous work has shown that TGF-beta blocks the
      TGF-alpha stimulation of type II cell proliferation. It appears that TGF-beta
      interferes with TGF-alpha-induced phosphorylation of the EGF-R.

PMID- 7529398
TI  - The neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) directly gates two ion channels
      in an identified Helix neurone.
AB  - FMRFamide (i.e. Phe-Met-Arg-Phe-NH2) application to the C2 neurone of Helix
      caused a depolarizing response which consisted of a large, rapidly developing,
      and rapidly desensitizing inward current, underlain by a smaller, slower inward
      current which did not desensitize. Both currents were carried through sodium
      selective channels which were insensitive to D-tubocurarine, and the to the fast
      sodium channel blockers tetrodotoxin (TTX) and lignocaine. Only the faster,
      desensitizing current could be blocked by amiloride. FMRFamide also activated two
      types of unitary inward currents with slightly differing amplitudes in outside
      out patches taken from the C2 neurone, both through sodium-selective ion
      channels. Only the smaller unitary currents readily desensitized and were
      susceptible to block by amiloride, and they also activated more rapidly. Unitary
      currents of both types were recorded in outside-out patches in the absence of
      freely diffusible intracellular mediators, and were also activated when guanosine
      5'-O-(2-thiodiphosphate) (GDP [beta-S]) was included in the recording pipette
      solution. This supports a tight receptor/channel coupling for both responses,
      with no involvement of GTP-binding proteins. Further, the very fast rate of
      activation of the smaller channels, which generally carry the major part of the
      FMRFamide-induced current, strongly indicates that these channels are ligand
      gated.

PMID- 7529399
TI  - Endothelium derived relaxing factor is involved in the pressure control of renin
      gene expression in the kidney.
AB  - To study the influence of endothelium derived relaxing factor/nitric oxide (EDNO)
      on renin gene expression, the effects of a 2-day treatment with the NO-synthase
      inhibitor nitro-L-arginine-methylester (L-NAME, 40 mg/kg twice a day) on plasma
      renin activity (PRA) and renal and adrenal renin m-RNA levels were examined in
      conscious rats with and without unilateral renal clips (0.2 mm). In sham-clipped
      animals L-NAME led to a decrease of PRA from 7.5 to 2.5 ng angiotensin (ANGI).h
      1.ml-1 and to a 35% decrease of renal renin m-RNA levels. Unilateral renal artery
      clipping increased PRA to 35 and to 13 ng ANGI.h-1.ml-1 in vehicle and in L-NAME
      treated rats, respectively. In the clipped kidneys renin m-RNA levels increased
      to 450% of control values in vehicle-treated animals and to 220% of control
      values in L-NAME-treated animals. In the contralaterals as opposed to clipped
      kidneys, renin m-RNA levels decreased to 16% and 50% of the control values in
      vehicle- and in L-NAME-treated animals, respectively. In the adrenal glands renin
      m-RNA levels were not significantly changed either by clipping of one renal
      artery or by treatment of animals with L-NAME. The NO-donor sodium nitroprusside
      (100 microM) was found to increase renin secretion and renin m-RNA levels in
      primary cultures of renal juxtaglomerular cells. These findings suggest that EDNO
      is involved in the control of the renin gene by the renal perfusion pressure.

PMID- 7529400
TI  - Charybdotoxin and iberiotoxin but not apamin abolish the slow after
      hyperpolarization in myenteric plexus neurons.
AB  - Myenteric neurons of guinea-pig ileum were studied with intracellular
      microelectrodes. The specific toxins charybdotoxin, iberiotoxin and apamin were
      used to characterize the prolonged after-hyperpolarizations of AH neurons in this
      preparation. Charybdotoxin and iberiotoxin blocked prolonged after
      hyperpolarizations in 23 of 24 AH neurons, but apamin had no effect on 5 of 5 AH
      neurons. Abolition of the after-hyperpolarizations was accompanied by
      depolarization and increases in input resistances of those AH neurons affected,
      but the shapes of action potentials were unchanged. The excitability of the AH
      neurons was enhanced as shown by an increase in the number of action potentials
      evoked by a 500-ms depolarizing current pulse or by a train of 15-ms depolarizing
      current pulses (10Hz). The other class of myenteric neurons, S neurons, was also
      investigated. The 19 S neurons studied fired action potentials only at the start
      of a 500 ms depolarization, but the toxins had no effect on this behaviour or on
      their other properties. Intracellular injection of Neurobiotin into the neurons
      studied and subsequent immunohistochemical staining to localise the calcium
      binding protein, calretinin, indicated that all major classes of S neurons were
      included in the sample. Thus, the prolonged after-hyperpolarizations in AH
      neurons may be due to opening of a large-conductance (BK) calcium-dependent
      potassium channel, but similar channels play little or no role in regulation of
      the excitability of S neurons.

PMID- 7529401
TI  - Effects of Mg2+ on Ca2+ handling by the sarcoplasmic reticulum in skinned
      skeletal and cardiac muscle fibres.
AB  - The influence of myoplasmic Mg2+ (0.05-10 mM) on Ca2+ accumulation (net Ca2+
      flux) and Ca2+ uptake (pump-driven Ca2+ influx) by the intact sarcoplasmic
      reticulum (SR) was studied in skinned fibres from the toad iliofibularis muscle
      (twitch portion), rat extensor digitorum longus (EDL) muscle (fast twitch), rat
      soleus muscle (slow twitch) and rat cardiac trabeculae. Ca2+ accumulation was
      optimal between 1 and 3 mM Mg2+ in toad fibres and reached a plateau between 1
      and 10 mM Mg2+ in the rat EDL fibres and between 3 and 10 mM Mg2+ in the rat
      cardiac fibres. In soleus fibres, optimal Ca2+ accumulation occurred at 10 mM
      Mg2+. The same trend was obtained with all preparations at 0.3 and 1 microM Ca2+.
      Experiments with 2,5-di-(tert-butyl)-1,4-benzohydroquinone, a specific inhibitor
      of the Ca2+ pump, revealed a marked Ca2+ efflux from the SR of toad iliofibularis
      fibres in the presence of 0.2 microM Ca2+ and 1 mM Mg2+. Further experiments
      indicated that the SR Ca2+ leak could be blocked by 10 microM ruthenium red
      without affecting the SR Ca2+ pump and this allowed separation between SR Ca2+
      uptake and SR Ca2+ accumulation. At 0.3 microM Ca2+, Ca2+ uptake was optimal with
      1 mM Mg2+ in the toad iliofibularis and rat EDL fibres and between 1 and 10 mM
      Mg2+ in the rat soleus and trabeculae preparations. At higher [Ca2+] (1 microM),
      Ca2+ uptake was optimal with 1 mM Mg2+ in the iliofibularis fibres and between 1
      and 3 mM Mg2+ in the EDL fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529402
TI  - Ca2+ signalling pathways activated by acetylcholine in mouse C2C12 myotubes.
AB  - In mouse C2C12 myotubes acetylcholine (ACh) elevates the concentration of
      myoplasmic Ca2+ ([Ca2+]i) by inducing Ca2+ influx through transmitter-gated and
      voltage-gated channels, and by mobilizing Ca2+ from internal stores. The relative
      contribution of each of these ACh-activated sources to the global [Ca2+]i
      elevation was estimated. We found that Ca2+ entry through voltage- and ACh-gated
      channels accounts for roughly 80% of the total [Ca2+]i increment, while
      mobilization from internal caffeine-sensitive and inositoltrisphosphate- (InsP3-)
      sensitive stores contributes the remaining 20% to the maximal [Ca2+]i increment.
      Furthermore, we found that ACh-induced mobilization from InsP3-sensitive stores
      also develops in embryonic chick myotubes. The differential importance of the
      Ca2+ signalling pathways activated by ACh during myogenesis is discussed.

PMID- 7529404
TI  - Modified RNA sequence pools for in vitro selection.
AB  - We report the use of modified RNA, in which the 2'-OH group of pyrimidines is
      replaced by a 2'-amino (2'-NH2) group to identify high affinity ligands specific
      for human neutrophil elastase (HNE) by in vitro selection. Compared to unmodified
      RNA the 2'-NH2-modified RNA ligands show enhanced stability in human serum and
      urine. Use of RNase T1 cleavage data in the presence of K+ and Li+ ions suggests
      that the modified RNA ligands selected for HNE form an intermolecular G-quartet
      structure.

PMID- 7529408
TI  - Computer-based prescribing.

PMID- 7529406
TI  - Sarkosyl block of transcription reinitiation by RNA polymerase II as visualized
      by the colliding polymerases reinitiation assay.
AB  - There are indications that different concentrations of Sarkosyl can block
      transcription initiation by RNA polymerase II in vitro at different functional
      steps [Hawley and Roeder (1985) J. Biol. Chem. 260, 8163-8172]. Consequently,
      this reagent could be a very useful tool for mechanistic studies. So far,
      however, evidence for the selectivity of Sarkosyl effects on RNA polymerase II
      transcription has been only indirect. To directly investigate the effect of
      Sarkosyl on transcription initiation and reinitiation by RNA polymerase II, we
      employed the reinitiation assay based on utilization of templates containing G
      free cassettes (colliding polymerases reinitiation assay, or CoPRA). These
      experiments showed unambiguously that, under the appropriate conditions, Sarkosyl
      can be used to block transcription reinitiation by RNA polymerase II while
      allowing a first round of initiations from preassembled initiation complexes.
      This inhibition is not due to a disruption of the SII-dependent elongation of the
      reinitiated transcripts, and the levels of Sarkosyl that prevent transcription
      reinitiation coincide with the levels that block preinitiation complex assembly.
      However, Sarkosyl addition to transcription reactions reconstituted with
      partially purified transcription factors was found to have several undesirable
      side effects. The usefulness and limitations of the Sarkosyl-based and CoPRA
      assays for measurements of transcription reinitiation are discussed.

PMID- 7529405
TI  - Exclusion of RNA strands from a purine motif triple helix.
AB  - Research concerning oligonucleotide-directed triple helix formation has mainly
      focused on the binding of DNA oligonucleotides to duplex DNA. The participation
      of RNA strands in triple helices is also of interest. For the pyrimidine motif
      (pyrimidine.purine.pyrimidine triplets), systematic substitution of RNA for DNA
      in one, two, or all three triplex strands has previously been reported. For the
      purine motif (purine.purine.pyrimidine triplets), studies have shown only that
      RNA cannot bind to duplex DNA. To extend this result, we created a DNA triple
      helix in the purine motif and systematically replaced one, two, or all three
      strands with RNA. In dramatic contrast to the general accommodation of RNA
      strands in the pyrimidine triple helix motif, a stable triplex forms in the
      purine motif only when all three of the substituent strands are DNA. The lack of
      triplex formation among any of the other seven possible strand combinations
      involving RNA suggests that: (i) duplex structures containing RNA cannot be
      targeted by DNA oligonucleotides in the purine motif; (ii) RNA strands cannot be
      employed to recognize duplex DNA in the purine motif; and (iii) RNA tertiary
      structures are likely to contain only isolated base triplets in the purine motif.

PMID- 7529407
TI  - Higher-order structure of bovine mitochondrial tRNA(SerUGA): chemical
      modification and computer modeling.
AB  - On the basis of enzymatic probing and phylogenetic comparison, we have previously
      proposed that mammalian mitochondrial tRNA(sSer) (anticodon UGA) possess a
      slightly altered cloverleaf structure in which only one nucleotide exists between
      the acceptor stem and D stem (usually two nucleotides) and the anticodon stem
      consists of six base pairs (usually five base pairs) [Yokogawa et al. (1991)
      Nucleic Acids Res. 19, 6101-6105]. To ascertain whether such tRNA(sSer) can be
      folded into a normal L-shaped tertiary structure, the higher-order structure of
      bovine mitochondrial tRNA(SerUGA) was examined by chemical probing using
      dimethylsulfate and diethylpyrocarbonate, and on the basis of the results a
      tertiary structure model was obtained by computer modeling. It was found that a
      one-base-pair elongation in the anticodon stem was compensated for by multiple
      base deletions in the D and extra loop regions of the tRNA(SerUGA), which
      resulted in preservation of an L-shaped tertiary structure similar to that of
      conventional tRNAs. By summarizing the findings, the general structural
      requirements of mitochondrial tRNAs necessary for their functioning in the
      mitochondrial translation system are considered.

PMID- 7529403
TI  - Modulation of guanylate cyclase and phosphodiesterase by monovalent cations and
      nucleoside triphosphates in light-sensitive excised patches of rod outer
      segments.
AB  - Excised inside-out patches of vertebrate rod outer segment can support
      phototransduction. I have examined how ionic and metabolic conditions influence
      the functional properties of light-sensitive patches from Gekko gekko. I find
      that such patches retain a variable level of basal phosphodiesterase activity,
      which lowers the cyclic guanosine monophosphate (cGMP) concentration reaching the
      channels and reduces the dark current. The dose/response relationship for channel
      opening by cGMP varies among patches and this variability is only reduced by
      working in darkness with the phosphodiesterase inhibitor 3-isobutyl-1-methyl
      xanthine (IBMX), suggesting that it is only partially due to phosphodiesterase
      activity. MgATP or MgGTP, but not Mg or ATP separately, increase this activity
      but a kinase does not appear to be involved. Intracellular monovalent cations
      also influence dark current intensity and light response kinetics. With 5 mM
      MgGTP, 1 mM IBMX, and 144 mM Li+, Na+, K+, or Rb+, dark current intensity and
      recovery time follow the respective sequences K+ > Rb+ > Na+ > Li+ and K+ < Rb+ <
      Li+ < Na+. Without IBMX, a dark current develops with K+ but not with Na+. These
      effects are not due to altered channel permeability (P)
      [PLi+:Na+:K+:Rb+:guanidinium)/PNa+ = 0.84:1.00:1.01:1.09:0.42], or differential
      Mg2+ block, but to modulation of guanylate cyclase, which overcomes
      phosphodiesterase when the major cation is K+ but not when it is Na+.

PMID- 7529409
TI  - Screening for prostate cancer.
AB  - PURPOSE/OBJECTIVES: To describe current prostate cancer screening methods and to
      address the controversies surrounding their use. DATA SOURCES: Published
      articles, abstracts, books, and press releases; personal communication. DATA
      SYNTHESIS: Controversy exists about whether efforts to conduct mass screenings
      for prostate cancer are of value given the related costs and the inability of
      such screenings to distinguish between indolent and aggressive tumors. The
      American Cancer Society (ACS) has added prostate cancer to its "Guidelines for
      the Cancer-Related Checkup" but does not recommend these guidelines for mass
      screenings. Preliminary findings of the ACS National Prostate Cancer Detection
      Study have shown that digital rectal examination (DRE) and transrectal
      ultrasonography (TRUS) have the best positive predictive value when the prostate
      specific antigen (PSA) level is greater than 4 ng/ml. CONCLUSIONS: Despite
      concern over the rising incidence of prostate cancer, the effectiveness of DRE,
      PSA, and TRUS in screening for early detection of prostate cancer remains
      controversial. IMPLICATIONS FOR NURSING PRACTICE: As the public becomes more
      aware of the controversies surrounding prostate cancer screening, nurses are
      finding that they play a vital role in the educational process. By understanding
      the abilities and deficiencies of the current screening methods, nurses can offer
      men concrete information about DRE, PSA, and TRUS. They can reinforce the
      importance of early detection for high-risk populations, as well as suggest
      strategies for encouraging compliance.

PMID- 7529410
TI  - [Kawasaki disease: apropos a case with pericardial effusion and persistent
      extrasystole].
AB  - The authors report a case of Kawasaki disease observed in a 3-years and 6-months
      old girl, with pericardial effusion and premature cardiac beats. The pericardial
      effusion disappeared after gamma-globulin i.v. treatment (2 gr/kg); the premature
      cardiac beats, although progressively reducing, completely disappeared only after
      6 months.

PMID- 7529411
TI  - Role of nitric oxide in control of prolactin release by the adenohypophysis.
AB  - Nitric oxide synthase-containing cells were visualized in the anterior pituitary
      gland by immunocytochemistry. Consequently, we began an evaluation of the
      possible role of NO in the control of anterior pituitary function. Prolactin is
      normally under inhibitory hypothalamic control, and in vitro the gland secretes
      large quantities of the hormone. When hemipituitaries were incubated for 30 min
      in the presence of sodium nitroprusside, a releaser of NO, prolactin release was
      inhibited. This suppression was completely blocked by the scavenger of NO,
      hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG
      is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO
      synthase. Incubation of hemipituitaries with either of these compounds
      significantly increased prolactin release. Since in other tissues most of the
      actions of NO are mediated by activation of soluble guanylate cyclase with the
      formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin
      release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin
      release. Prolactin release in vivo and in vitro can be stimulated by several
      peptides, which include vasoactive intestinal polypeptide and substance P.
      Consequently, we evaluated the possible role of NO in these stimulations by
      incubating the glands in the presence of either of these peptides alone or in
      combination with NMMA. In the case of vasoactive intestinal polypeptide, the
      significant stimulation of prolactin release was augmented by NMMA to give an
      additive effect. In the case of substance P, there was a smaller but significant
      release of prolactin that was not significantly augmented by NMMA. We conclude
      that NO has little effect on the stimulatory action of these two peptides on
      prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release,
      reduced prolactin release, and this inhibitory action was significantly blocked
      by either hemoglobin (20 micrograms/ml) or NMMA and was completely blocked by 1
      mM nitroarginine methyl ester. Atrial natriuretic factor at 1 microM also reduced
      prolactin release, and its action was completely blocked by NMMA. In contrast to
      these results with prolactin, luteinizing hormone (LH) was measured in the same
      medium in which the effect of nitroprusside was tested on prolactin release,
      there was no effect of nitroprusside, hemoglobin, or the combination of
      nitroprusside and hemoglobin on luteinizing hormone release. Therefore, in
      contrast to its inhibitory action on prolactin release NO had no effect on
      luteinizing hormone release. Immunocytochemical studies by others have shown that
      NO synthase is present in the folliculostellate cells and also the gonadotrophs
      of the pituitary gland. We conclude that NO produced by either of these cell
      types may diffuse to the lactotropes, where it can inhibit prolactin release. NO
      appears to play little role in the prolactin-releasing action of vasoactive
      intestinal polypeptide and substance P, but mediates the prolactin-inhibiting
      activity of dopamine and atrial natriuretic factor.

PMID- 7529413
TI  - O2-sensitive K+ currents in carotid body chemoreceptor cells from normoxic and
      chronically hypoxic rats and their roles in hypoxic chemotransduction.
AB  - Carotid body-mediated ventilatory increases in response to acute hypoxia are
      attenuated in animals reared in an hypoxic environment. Normally, O2-sensitive K+
      channels in neurosecretory type I carotid body cells are intimately involved in
      excitation of the intact organ by hypoxia. We have therefore studied K+ channels
      and their sensitivity to acute hypoxia (PO2 12-20 mmHg) in type I cells isolated
      from neonatal rats born and reared in normoxic and hypoxic environments. When
      compared with cells from normoxic rats, K+ current density in cells from hypoxic
      rats was significantly reduced, whereas Ca2+ current density was unaffected.
      Charybdotoxin (20 nM) inhibited K+ currents in cells from normoxic rats by
      approximately 25% but was without significant effect in cells from hypoxic rats.
      However, hypoxia caused similar, reversible inhibitions of K+ currents in cells
      from the two groups. Resting membrane potentials (measured at 37 degrees C using
      the perforated-patch technique) were similar in normoxic and hypoxic rats.
      However, although acute hypoxia depolarized type I cells of normoxic rats, it was
      without effect on membrane potential in type I cells from hypoxic animals.
      Charybdotoxin (20 nM) also depolarized cells from normoxic rats. Our results
      suggest that type I cells from chronically hypoxic rats, like normoxic rats,
      possess O2-sensing mechanisms. However, they lack charybdotoxin-sensitive K+
      channels that contribute to resting membrane potential in normoxically reared
      rats, and this appears to prevent them from depolarizing (and hence triggering
      Ca2+ influx and neurosecretion) during acute hypoxia.

PMID- 7529412
TI  - FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in
      bone marrow and testis.
AB  - PR-39, a proline/arginine-rich peptide antibiotic, has been purified from pig
      intestine and later shown to originate in the bone marrow. Intending to isolate a
      clone for a human counterpart to PR-39, we synthesized a PCR probe derived from
      the PR-39 gene. However, when this probe was used to screen a human bone marrow
      cDNA library, eight clones were obtained with information for another putative
      human peptide antibiotic, designated FALL-39 after the first four residues. FALL
      39 is a 39-residue peptide lacking cysteine and tryptophan. All human peptide
      antibiotics previously isolated (or predicted) belong to the defensin family and
      contain three disulfide bridges. The clone for prepro-FALL-39 encodes a cathelin
      like precursor protein with 170 amino acid residues. We have postulated a dibasic
      processing site for the mature FALL-39 and chemically synthesized the putative
      peptide. In basal medium E, synthetic FALL-39 was highly active against
      Escherichia coli and Bacillus megaterium. Residues 13-34 in FALL-39 can be
      predicted to form a perfect amphiphatic helix, and CD spectra showed that medium
      E induced 30% helix formation in FALL-39. RNA blot analyses disclosed that the
      gene for FALL-39 is expressed mainly in human bone marrow and testis.

PMID- 7529414
TI  - The chemistry of signal transduction.
AB  - Several disciplines, including chemical ecology, seek to understand the molecular
      basis of information transfer in biological systems, and general molecular
      strategies are beginning to emerge. Often these strategies are discovered by a
      careful analysis of natural products and their biological effects. Cyclosporin A,
      FK506, and rapamycin are produced by soil microorganisms and are being used or
      considered as clinical immunosuppressive agents. They interrupt the cytoplasmic
      portion of T-cell signaling by forming a complex with a binding protein--FKBP12
      in the case of FK506 and rapamycin and cyclophilin A (CyPA) in the case of
      cyclosporin A (CsA). This complex in turn inhibits a protein target, and the best
      understood target is calcineurin, which is inhibited by FK506-FKBP12 and CyPA
      CsA. Mutational and structural studies help define how FK506-FKBP12 interacts
      with calcineurin, and the results of these studies are summarized. The existence
      of strong FK506-FKBP12 binding suggests that FK506 is mimicking some natural
      ligand for FKBP12. Synthetic and structural studies to probe this mimicry are
      also described.

PMID- 7529415
TI  - Growth of fibroblasts as a potential confounding factor in soft agar clonogenic
      assays for tumour cell radiosensitivity.
AB  - Soft agar clonogenic assays are considered to be a standard method for measuring
      tumour cell radiosensitivity and it has been widely reported that fibroblast
      contamination does not occur. We report here that human fibroblasts can
      proliferate to form colonies in a modified form of the Courtenay-Mills soft agar
      clonogenic assay. It was observed that early passage skin fibroblasts could form
      colonies in soft agar, although the plating efficiencies were reduced compared
      with growth on plastic. It was demonstrated that normal lung could proliferate in
      agar with similar plating efficiencies to fresh tumours and that fibroblastic
      cells were present in these cultures. Characterisation of primary lung tumour
      cultures also showed that fibroblastic cells were present in these cultures.
      Characterisation of primary lung tumour cultures also showed that fibroblastic
      cells were present which lacked epithelial features and which resembled closely
      the cells found in cultures of normal lung. This is an important finding for
      workers using soft agar assays to culture human tumour cells and is of interest
      in understanding the processes of normal growth control of human fibroblasts.

PMID- 7529417
TI  - Influence of anti-inflammatory treatments on experimental infection of rats with
      Fasciola hepatica: changes in serum levels of inflammatory markers during the
      early stages of fasciolosis.
AB  - Anti-inflammatory treatments with dexamethasone, indomethacin or aspirin shortly
      before or immediately after the experimental infection of rats with Fasciola
      hepatica resulted in an increase in the rats' burden of adult flukes, suggesting
      that the inflammatory system played an active part in the rats' immune defense
      against invasive F hepatica. An anti-parasitic effect of cyclosporin A on F
      hepatica infection in rats was also demonstrated. A weekly study of various
      inflammatory markers (acute phase proteins, leucocytes and platelets)
      demonstrated that no inflammatory reaction had occurred after the first two weeks
      of infection, but that there was a significant increase in acute phase proteins
      after three and four weeks. These increases indicated that a chronic inflammatory
      reaction, associated with liver damage and an increasing eosinophilia, had
      occurred.

PMID- 7529418
TI  - Influence of pro-inflammatory treatments on experimental infection of rats with
      Fasciola hepatica: changes in serum levels of inflammatory markers during the
      early stages of fasciolosis.
AB  - The effect of stimulating an inflammatory reaction by injecting rats with either
      Freund's complete adjuvant or turpentine oil shortly before or after they were
      infected experimentally with Fasciola hepatica on the establishment of the
      parasite was studied. Freund's complete adjuvant, given either four hours before
      or four hours after infection with F hepatica and turpentine oil given four hours
      before infection resulted in a 40 to 50 per cent decrease in the rats' fluke
      burden. The study of markers of inflammation (acute phase proteins, leucocytes
      and platelets) demonstrated that the fluke had a modulating effect on the rat's
      inflammatory response. During the first few days after infection, F hepatica
      stimulated a transitory inflammatory reaction, as suggested by changes in the
      level of acute phase proteins (APP) in the serum. No further change in the APP
      titre occurred until three weeks after infection, when, together with an increase
      in the extent of the liver lesions, the change in the titre of APP indicated that
      a systemic and chronic inflammatory process had taken place.

PMID- 7529419
TI  - Recombinant vaccinia virus expressing PrM and E glycoproteins of louping ill
      virus: induction of partial homologous and heterologous protection in mice.
AB  - Recombinant vaccinia viruses expressing either the premembrane/truncated envelope
      (PrM/TrE) or truncated envelope (TrE) protein of louping ill virus were
      constructed. Both constructs expressed authentic E proteins as determined by
      their size and antigenic reactivity with a panel of monoclonal antibodies. The
      deletion of the C-terminal hydrophobic domain of the envelope glycoprotein
      resulted in the secretion of E protein into the supernatant culture medium. The
      immunisation of mice with these recombinant viruses showed that the recombinant
      expressing PrM/TrE proteins induced neutralising and protective antibodies
      against challenge with louping ill or tick-borne encephalitis virus, but that the
      recombinant expressing the E or the TrE protein alone failed to induce any
      detectable immune responses against homologous or heterologous virus challenge.

PMID- 7529416
TI  - Preparation of monoclonal antibodies specific for the subclasses of canine IgG.
AB  - Canine IgG is composed of four subclasses, which are defined as IgG1, IgG2, IgG3
      and IgG4 on the basis of data from fast protein liquid chromatography, and their
      electrophoretic mobilities and relative concentrations in serum. This paper
      describes the preparation of mAbs specific for determinants on canine IgG2, IgG3
      and IgG4. The mAb specific for IgG2 resulted from a conventional immunisation
      protocol. The mAb specific for IgG3 was a result of immunisation with IgG3
      combined with the suppression of the immune response to IgG1 by passively
      administered anti-IgG1 antibody. The mAb specific for IgG4 resulted from
      immunisation with Fab or Fc fragments which were obtained by the cleavage of the
      IgG4 molecule with papain. The specificity of each mAb was established by using
      an enzyme-linked immunosorbent assay which showed that all three specific clones
      recognised a determinant in the Fd region of the canine immunoglobulin molecule.

PMID- 7529420
TI  - Recurrent choroidal neovascularization after laser photocoagulation in Sorsby's
      fundus dystrophy.
AB  - BACKGROUND: Patients with autosomal dominant Sorsby's fundus dystrophy are at
      high risk of severe visual loss due to choroidal neovascularization (CNV) during
      the fourth or fifth decade of life. METHODS: To assess the efficacy of argon
      laser photocoagulation for extrafoveal well-defined CNV, we analyzed
      retrospectively the clinical course in 10 eyes of 7 patients who had Sorsby's
      fundus dystrophy with CNV 200 microns to 2,500 microns from the center of the
      foveal avascular zone, and who subsequently underwent laser photocoagulation.
      RESULTS: All treated eyes developed severe visual loss as a consequence of
      recurrent or persistent CNV occurring on the foveal side of the treatment scar,
      which extended under the fovea. The average time until occurrence of
      angiographically documented CNV after initial treatment was 8.1 +/- 8.9 weeks,
      but ranged from 2 weeks to 32 weeks. Retreatment for persistent or recurrent
      extrafoveal CNV was performed in 5 eyes, but CNV recurred in all 5. CONCLUSIONS:
      Results of this study suggest that the risk of persistence or recurrence of CNV
      after laser photocoagulation for extrafoveal CNV is unusually high in patients
      with Sorsby's fundus dystrophy, and that this treatment is ineffective in
      preventing severe visual loss in such patients.

PMID- 7529421
TI  - Epiretinal membranes in Tersons syndrome. A clinicopathologic study.
AB  - BACKGROUND: Visual impairment resulting from retinal, subhyaloid, or vitreous
      hemorrhages in association with Tersons syndrome is often significant. The most
      common long-term sequelae that may result in permanent visual deficit is the
      formation of an epimacular membrane. METHODS: This report provides
      clinicopathologic documentation of epiretinal membrane proliferation secondary to
      Tersons syndrome. Pars plana vitrectomy was performed in 16 eyes of 11 patients
      with Tersons syndrome. After removal of vitreous hemorrhage, epimacular membranes
      were found in 10 eyes (62.5%). The posterior cortical vitreous and the epiretinal
      tissue were examined histologically. RESULTS: Immunostainings with glial and
      retinal pigment epithelial cell markers showed that the majority of cells derived
      form the glia. Perls staining, specific for iron, showed that the high melanic
      like component contained in the histopathologic samples corresponded to
      degradation of blood products secondary to chronic hemorrhage. CONCLUSION: The
      high risk of epiretinal membrane formation and the toxicity of blood breakdown
      products over the inner retina worsen the long-term visual prognosis in Tersons
      syndrome. Early surgery is advocated in such cases.

PMID- 7529422
TI  - Acute bilateral optic disc neovascularization.
AB  - PURPOSE: A case of bilateral acute neovascularization of the optic disc and
      peripapillary epiretina of unknown etiology in a previously healthy 26-year-old
      woman is discussed. METHODS: The clinical course of the disease, investigation,
      and treatment are presented in detail. RESULTS: Histopathologic examination of
      epiretinal tissue removed from the second eye at vitrectomy provided evidence of
      inflammatory disease and suggested a possible etiology. CONCLUSION: The cause of
      this patient's disease remains uncertain. Known causes of this disease were
      excluded as far as possible. Histopathologic examination of the epiretinal
      membrane from the second eye demonstrated an unusually increased inflammatory
      response and multiple intracytoplasmic inclusion bodies in neutrophils resembling
      mollicute-like organisms.

PMID- 7529425
TI  - The retrocuspid papilla and factor XIIIa: an epidemiologic and histomorphologic
      study.
AB  - The retrocuspid papilla (RCP) is a poorly recognized entity. In one part of our
      study, we found 10 cases of lesions clinically compatible with RCP in 1150
      consecutively examined patients. In another part of the study, we found 15 cases
      of RCP in more than 2000 consecutive cases of oral mucosal hyperplasia submitted
      as surgical biopsies during 1989-92. The lesions were situated in the attached
      gingiva, lingual to the two mandibular canines, often bilaterally. They were
      covered by normal pink mucosa with a size and a height each of 2-3 mm.
      Histologically, the RCP was a broad-based, often downfolded hyperplasia, covered
      with a parakeratinized epithelium of normal thickness. The rete pegs were often
      elongated and blunt, frequently bent inward toward the center. The lamina propria
      was mostly composed of a loosely arranged, delicate, fibrous connective tissue.
      The lesions could be classified into two groups by the presence or absence of
      stellate and occasionally multinucleated fibroblasts. Immunohistochemical
      staining with an FXIIIa antibody disclosed a population of reactive spindle
      shaped cells, mainly localized in the connective-tissue papillae. These cells may
      be of pathogenetic importance.

PMID- 7529424
TI  - Metal accumulation and nephron heterogeneity in mercuric chloride-induced acute
      renal failure.
AB  - The present study was designed to assess the effects of mercury on glomerular
      integrity during the early phase of acute renal failure. The silver amplification
      method showed distribution of mercury in midcortical and juxtamedullary glomeruli
      and on the brush border of the S2 segment of the proximal tubule 15 min after
      treatment. At 30 min, there was a decrease in glomerular staining and increased
      mercury in the proximal tubule. After 3 hr, mercury was no longer detectable in
      glomeruli but was widespread in the lumen of the proximal tubule. By 24 hr,
      mercury was prominent in all proximal tubular segments throughout the cortex. The
      presence of mercury in glomeruli was not related to hemodynamic changes, as there
      was no evidence for blood redistribution toward juxtamedullary glomeruli as
      assessed by the filling of the microvascular system with Monastral Blue B. The
      reduced activity of horseradish peroxidase (administered i.v. 90 sec and 10 min
      before sacrifice) in juxtamedullary glomeruli 30 min after mercury administration
      suggests a decreased uptake of horseradish peroxidase or an increased glomerular
      protein filtration. These data support glomerular filtration as the predominant
      excretory route for mercury, highlight the marked nephron heterogeneity in the
      distribution of this metal, and show that impairment of glomerular integrity
      occurs before necrosis of the proximal tubules and acute renal failure.

PMID- 7529426
TI  - Comparison of three test methods used for the diagnosis of candidiasis.
AB  - A total of 266 specimens was taken from oral mucosa or dentures of 88 patients
      with suspected Candida-infected oral mucosa. One-third of the debris from each
      sample was cultured on Microstix-Candida (C), strips, one-third was cultured on
      Oricult-N-plates, and the rest was collected on glass plates and stained by the
      periodic acid-Schiff (PAS) method. The PAS-stained samples were analyzed under
      the light microscope for the presence of Candida hyphae. The other samples
      (Oricult-N or Microstix-C) were studied visually, according to the manufacturer's
      recommendation. PAS-stained specimens showed significantly less often positive
      results than those of the two culture methods. These data suggest that oral
      candidiasis may be incorrectly diagnosed if based upon results obtained with the
      culture methods. It is also possible that the PAS-staining method yielded false
      negative findings. This possibility should always be considered, especially if
      other findings and symptoms disagree with the test results obtained.

PMID- 7529423
TI  - Tachykinins induce a [Ca2+]i rise in the acinar cells of feline tracheal
      submucosal gland.
AB  - The intracellular Ca2+ concentration ([Ca2+]i) of acinar cells of isolated
      submucosal glands from trachea was measured using a fluorescent dye, Fura-2.
      Neurokinin A (NK-A) produced a sustained rise in [Ca2+]i in a dose-dependent
      manner, reaching a response of 500 to 600% of the prior baseline value at 10(-6)
      or 10(-5) M, and the NK-A evoked [Ca2+]i was significantly higher than that by
      substance P (SP) at similar concentrations. NK-B did not induce significant
      increases in [Ca2+]i. In a Ca(2+)-free solution, NK-A produced a transient rise
      in [Ca2+]i, which returned to the baseline within 3 min. Mucus glycoprotein (MGP)
      secretion, estimated by measuring trichloroacetic-acid (TCA) precipitable
      glycoconjugates, was stimulated by NK-A or SP. These findings indicate that
      tachykinins produce a rise in [Ca2+]i by both entry from the extracellular
      solution and release from intracellular storage, probably by NK-2 receptor
      stimulation, and stimulate MGP secretion from airway submucosal glands.

PMID- 7529427
TI  - Prognosis in bladder cancer. A study of cytometric, morphometric and
      immunohistochemical techniques.
AB  - Bladder cancer affects about 2,000 people in Sweden every year. For adequate
      treatment, prognostic information is essential. Most of the prognostic factors
      applied to date still lack satisfactory predictive value. This investigation was
      conducted on 230 bladder tumours with a known prognosis in order to improve
      prognostication methods. A new modified technique for the measurement of the DNA
      content in formalin-fixed paraffin-embedded bladder tumour tissue was developed,
      by introducing a new enzyme and density gradient centrifugation before performing
      flow cytometry. The results were comparable with those obtained by analysing
      fresh or frozen tissue. DNA ploidy was found to correlate positively to stage,
      histological grade and progression. A methenamine-silver staining technique,
      which facilitates the identification of mitoses, was developed and applied for
      determining mitotic frequency and density. The results proved to yield prognostic
      markers superior to subjective grading. Intermediate grade tumours could be
      separated into two prognostically highly different groups. Reduced PCNA
      antigenicity in archival, formalin-fixed, paraffin-embedded bladder tumour tissue
      was observed. Antigen expression could be retrieved by heating the slides in
      distilled water in a microwave oven. The application of a citrate buffer could
      further improve the staining, which correlated to prognosis but had no
      independent prognostic value. Image analysis was applied in an attempt to develop
      computer-based grading systems. Analysis of Feulgen-stained tissue sections was
      performed by an object-based method, digitizing, segmenting and analyzing the
      images automatically. Furthermore, a texture analysis method, which estimated
      grey-scale co-occurrence probability matrices on digitized images, was developed;
      both types of grading were found to correlate significantly to subjective
      grading.

PMID- 7529429
TI  - Clinical utility of cellular DNA measurements in prostate carcinoma. Consensus
      Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer.
      Stockholm, Sweden, May 12-13, 1993.
AB  - At a WHO consensus conference on Early Diagnosis and Prognostic Parameters in
      Localized Prostate Cancer, a working group discussed the clinical utility of DNA
      measurements in stages T2 and T3 prostate carcinoma. Incidentally discovered
      prostate cancer of stage T1 was excluded. The members of the working group,
      representing various clinical and laboratory disciplines, discussed technical
      considerations of DNA measurements by flow and image analysis, pretreatment
      prediction of prognosis, and posttreatment clinical relevance. The group agreed
      to subdivide tumors into diploid, tetraploid and non-tetraploid aneuploid,
      expressing various degrees of aggressiveness and gave guidance for the definition
      of limits of these groups. The panel agreed that knowledge on DNA ploidy prior to
      treatment is of value in treatment decisions, particularly when surveillance is a
      treatment option. Aneuploid tumors can be expected to respond very poorly to
      either irradiation or endocrine therapy, and the presence of aneuploid tumor,
      either on pretreatment biopsies or in radical prostatectomy specimens, is an
      ominous sign. The identification of a group of patients with a uniformly poor
      prognosis should encourage medical oncologists and basic scientists to develop
      adequate treatment options for this particular group. The panel expressed a
      strong opinion that DNA ploidy should be uniformly studied in clinical trials,
      particularly in patients with localized prostate cancer.

PMID- 7529428
TI  - The TNM system of 1992. Comments from the TNM working group. Consensus Conference
      on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm,
      Sweden, May 12-13, 1993.
AB  - The TNM working group acknowledges the multinational agreement reached in the
      1992 TNM classification, but nevertheless gives some suggestions for
      modifications. The main interest of the group has been to evaluate parameters
      suitable for further ramification of the system. The group found that parameters
      such as DNA ploidy, PSA, nuclear roundness factor, are not yet ready for this
      purpose. Grade is an established parameter and should be incorporated into the
      TNM-categories of localized disease. In metastatic disease a number of parameters
      are available to subdivide this category according to prognosis, and these will
      be more uniformly and extensively studied in the several large trials that are
      now in progress.

PMID- 7529430
TI  - Tumor markers. Consensus Conference on Diagnosis and Prognostic Parameters in
      Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.
AB  - This chapter mainly deals with biochemical aspects on prostate specific antigen
      (PSA) and its clinical value. To a limited extent, also other tumor markers,
      which might be of importance in the evaluation of patients with prostate cancer
      are discussed. In serum, PSA exists in a free form or bound to antichymotrypsin.
      Interestingly, only 10% of PSA secreted from cancer cells seems to exist in a
      free form, as compared to 30% of PSA secreted from cells in benign prostatic
      hyperplasia (BPH). PSA seems to be closely, but not absolutely, related to tumor
      grade and stage. The mean value of PSA in patients with tumors dominated by
      Gleason grades 3 or below, was 10 ng/ml, compared to 29 ng/ml in those with
      higher grades. Patients with PSA values of 50 ng/ml or above almost exclusively
      had tumor of Gleason grades 4 or 5, and this limit usually reflected a
      generalized disease. Patients with PSA-values below 10 ng/ml almost exclusively
      had tumors confined to the prostate gland. In countries where screening for
      prostate cancer is believed in, it is important to understand that normal cut-off
      values are related to patient's age. The upper normal limit of males below 50
      years of age should be set at 2.5 ng/ml, as compared to 6.5 ng/ml for men over 70
      years of age. To improve the value of PSA determination and for scientific
      purposes, the standardization of the assay is urgently needed and under way.
      Prostate acid phosphatase (PAP) has in most centres been replaced by PSA. An
      elevated PAP value, as measured by the enzymatic method, invariably indicates a
      generalized disease and could thus be used as a complementary informative assay
      to PSA. Other markers have been used mainly to achieve additional prognostic
      information. In a multivariate analysis, the non-specific tumor marker neopterin,
      which reflects the host response to tumor antigens, was closely related to short
      term prognosis. Neopterin was followed by thymidine kinase, a protein reflecting
      the cell turn-over and tumor grade. Also PSA at diagnosis seemed to add some
      prognostic information, whereas other markers did not.

PMID- 7529432
TI  - A survey concerning the attitudes of urologists toward prostatism patients.
AB  - In a questionnaire all urological units in Norway were asked about: 1. The
      examinations they routinely used for prostatism patients before deciding upon
      treatment. 2. How they would score different objective and subjective information
      about these patients on a scale from 0 to 10. 3. How the physicians classified
      different prostatism symptoms into categories of weak, moderate and severe. The
      results were: Urinary retention occurring more than once or residual urine
      greater than 500 ml was considered an absolute indication for surgery. Agreement
      about indications for surgery was good for information which received a high
      median score, but was much poorer for information which received a lower median
      score. Agreement on how to classify different symptoms into categories according
      to severity was not good. Using the median classification of symptoms it was
      estimated that urologists believe that 0.1-5.8% of men over 60 years of age have
      severe symptoms, 2.1-36.4% have moderate symptoms and 57.8-97.8% weak or no
      symptoms.

PMID- 7529431
TI  - Imaging in the diagnosis and assessment of prognosis in localized prostate
      cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized
      Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.
AB  - As part of a WHO consensus conference on diagnosis and prognostic parameters in
      localized prostate cancer, a working group of experts discussed the role of
      various modern imaging techniques. Special attention was focused on transrectal
      ultrasound (TRUS) in combination with biopsies, magnetic resonance imaging (MRI)
      using endorectal coil and recent advances in these techniques. Some experimental
      techniques, especially hormone receptor scintigraphy and positron emission
      tomography were also discussed and new results were presented. We concluded that
      MRI seems to be superior to other imaging techniques in the preoperative
      assessment of local tumor stage. TRUS defends its place in the diagnostic
      armament; it is easily combined with multiple biopsies, the results of which are
      important in the assessment of the biological aggressiveness of prostate cancer.
      The present development in the field of nuclear medicine may result in techniques
      for in vivo characterization of tumors and will most certainly have important
      implications for diagnosis of prostate cancer in the future.

PMID- 7529433
TI  - The institutionalization of the good death.
AB  - There has been some recent concern in Britain and North America that the
      increasing institutionalization of hospice care may compromise the movement's
      founding ideals. The threats posed by the encroachment of mainstream medicine and
      the medical technological imperative to treat, are also a source of concern to
      hospice administrators and staff. This study uses Australian data based on
      interviews with nurses and participant observation in an in-patient hospice unit
      and a community based hospice service to investigate whether the Good Death
      ideal, as central to the hospice philosophy, is compatible with the
      institutionalization of hospice care. The issues that arise, although
      interrelated are conceptualized as the following five challenges to hospice care:
      (1) encroachment of mainstream medicine and the medical technical imperative; (2)
      competing motivations; (3) delimitation of intellectual structures; (4)
      organizational maintenance; and (5) routinization of the Good Death. This
      conceptual framework is based on the way in which nurses and other health care
      professionals have used shared logic and strategies to negotiate the daily
      demands of their work and illustrates the tension that arises between the
      maintenance of the ideal and the maintenance of the organization.

PMID- 7529434
TI  - Pathogenesis, recognition, and management of common cardiac arrhythmias. Part I:
      Ventricular premature beats and tachyarrhythmias.
AB  - Cardiac arrhythmias are disorders of impulse formation, impulse conduction, or
      both. Part I of this two-part review discusses clinically relevant cardiac
      electrophysiology, as well as the pathogenesis, recognition, and management of
      ventricular premature beats and ventricular tachyarrhythmias. Part II will review
      the pathogenesis, recognition, and management of supraventricular premature beats
      and supraventricular tachyarrhythmias.

PMID- 7529435
TI  - Single channel currents in the nicotinic acetylcholine receptor: a direct
      demonstration of allosteric transitions.

PMID- 7529436
TI  - Aquaporins: water channel proteins of plant and animal cells.
AB  - Certain biological membranes, such as the erythrocyte plasma membrane, have a
      high osmotic water permeability, and such membranes have long been suspected of
      harboring water channels. The molecular identity of these channels has now been
      established with the purification of water-channel proteins and the cloning of
      the genes encoding them. Homologous water-channel proteins, called 'aquaporins',
      are present in plants and animals. These channels are water selective and do not
      allow ions or metabolites to pass through them. Their discovery is providing new
      insights into how plant and animal cells facilitate and regulate the passage of
      water through their membranes.

PMID- 7529437
TI  - Regeneration in the auditory system: lessons from other epithelia, and persisting
      puzzles.

PMID- 7529439
TI  - Patchiness as a means to get a message across.

PMID- 7529440
TI  - Signal integration in the olfactory system.

PMID- 7529441
TI  - Nerve-terminal proteins: to fuse to learn.
AB  - Transmitter release and membrane expansion involves the fusion of specialized
      vesicles to their target membranes. The mechanisms that regulate these fusion
      events might contribute to short- and long-term changes of synaptic efficiency
      that are associated with learning. A series of recently described protein-protein
      interactions has shed new light on vesicle binding to the cytoskeleton, vesicle
      docking to the target membranes and, finally, vesicle fusion and membrane
      retrieval. Specific steps in this pathway might be key sites for modulating the
      strength of synaptic connections that underlie the molecular basis of learning.

PMID- 7529442
TI  - Effects of neuropeptide Y on the electrical properties of neurons.
AB  - Neuropeptide Y, one of the scions of the pancreatic polypeptide family, is found
      throughout the nervous system. Based on its abundance alone, one would expect
      neuropeptide Y to play an important role in the regulation of neuronal activity,
      and indeed many pharmacological studies have demonstrated neuromodulatory effects
      of neuropeptide Y. Here, William F. Colmers and David Bleakman review the known
      actions of neuropeptide Y on the electrical properties of nerve cells.
      Neuropeptide Y inhibits Ca2+ currents, and modulates transmitter release in a
      highly selective manner. Neuropeptide Y might be quite important in the
      regulation of neuronal state, as exemplified by its actions in the hippocampus
      and the dorsal raphe nucleus.

PMID- 7529443
TI  - Magnetoencephalography in studies of human cognitive brain function.
AB  - Magnetoencephalography provides a new dimension to the functional imaging of the
      brain. The cerebral magnetic fields recorded noninvasively enable the accurate
      determination of locations of cerebral activity with an uncompromized time
      resolution. The first whole-scalp sensor arrays have just recently come into
      operation, and significant advances are to be expected in both neurophysiological
      and cognitive studies, as well as in clinical practice. However, although the
      accuracy of locating isolated sources of brain activity has improved,
      identification of multiple simultaneous sources can still be a problem.
      Therefore, attempts are being made to combine magnetoencephalography with other
      brain-imaging methods to improve spatial localization of multiple sources and,
      simultaneously, to achieve a more complete characterization of different aspects
      of brain activity during cognitive processing. Owing to its good time resolution
      and considerably better spatial accuracy than that provided by EEG,
      magnetoencephalography holds great promise as a tool for revealing information
      processing sequences of the human brain.

PMID- 7529438
TI  - Triggering and execution of neuronal death in brain ischaemia: two phases of
      glutamate release by different mechanisms.
AB  - A reduced blood or oxygen supply to the brain leads to neuronal death caused by
      excessive activation of glutamate receptors. Recent evidence suggests that two
      distinct phases of glutamate release produce this death. During ischaemia or
      hypoxia, glutamate is released by reversed operation of glutamate uptake
      carriers. It activates N-methyl-D-aspartate (NMDA) receptors, increases the
      intracellular concentration of Ca2+, and triggers a long-lasting potentiation of
      NMDA-receptor-gated currents. After ischaemia, glutamate released by Ca(2+)
      dependent exocytosis activates an excessive influx of Ca2+ largely through
      potentiated NMDA-receptor-channels, which leads to neuronal death. The
      therapeutic implications of such a scheme are discussed.

PMID- 7529444
TI  - Dyeing: a simple method for detecting positive or negative surgical margins.
AB  - Artists' pigments have been used in more than 150 radical prostatectomy specimens
      and many other malignant surgical specimens for detecting positive surgical
      margins. Their advantages are rapid drying, resistance to tissue processing, and
      the ability to mark many planes of excision simultaneously with different colors.

PMID- 7529446
TI  - Intraprostatic ethanol injection prior to transurethral resection of the prostate
      for prevention of perioperative blood loss.

PMID- 7529445
TI  - A new self-expansive intraurethral stent using shape memory alloy: a preliminary
      report of its availability.
AB  - OBJECTIVES: We describe a new stent made from shape memory alloy (SMA) first
      developed by our collaborative group, its structure, and a simple and easy
      procedure for its placement and removal without the need for a monitoring system
      or sedation. METHODS: The stent made of SMA was placed in 5 dogs for 10 months.
      It was left in situ in the shape of thermal expansion while the obturator Foley
      catheter was removed. RESULTS: Placement and removal of the stent was very easy
      and quick on each occasion in all 5 dogs. No proximal or distal dislodgement was
      observed in 5 dogs during the indwelling period. There was no encrustation of
      calcification on the surface of the stent at its removal. CONCLUSIONS: These
      preliminary results suggest that the SMA spiral stent might be an alternative for
      the relief of prostatic obstruction and be well tolerated in patients with
      bladder outlet obstruction. The SMA spiral stent is being developed for clinical
      use.

PMID- 7529447
TI  - Transurethral needle ablation of the prostate for treatment of benign prostatic
      hyperplasia: early clinical experience.
AB  - OBJECTIVES: Many attempts have been made to develop a method for treatment of
      benign prostatic hyperplasia (BPH) that is minimally invasive, efficacious, and
      low-cost. Transurethral needle ablation (TUNA) is a new, fast outpatient
      anesthesia-free procedure, using interstitial low-level radio frequency energy to
      produce a temperature above 100 degrees C. We describe our early clinical
      experience with TUNA as an outpatient procedure. METHODS: This technique was used
      in 20 patients with symptomatic BPH. All men were evaluated prior to treatment
      with flow rates, residual urine, International Prostate Symptom Score (IPSS), and
      quality of life. Follow-up occurred at 3 and 6 months after treatment, analyzing
      the same parameters. RESULTS: Tolerance using topical anesthetic and intravenous
      diazepam was excellent. Peak flow rate increased from a mean 9.5 +/- 3.3 mL/s to
      14.7 +/- 6.3 mL/s (P < 0.05) at 3 months (19 patients) and to 15.0 +/- 4.9 mL/s
      (P < 0.05) at 6-month follow-up (12 patients). IPSS and quality of life improved
      from an average of 21.9 +/- 5.0 and 4.4 +/- 0.7 (P < 0.005) to 10.2 +/- 4.8 and
      2.4 +/- 1.2 (P < 0.005), respectively, at 3-month follow-up. No significant
      complications were encountered. Retention was observed in 25% of the cases after
      the TUNA treatment. CONCLUSIONS: This initial study demonstrates the safety and
      effectiveness of TUNA. TUNA is a promising, anesthesia-free alternative treatment
      for men with symptomatic BPH. Long-term follow-up and randomized comparative
      studies with transurethral resection of the prostate (TURP) are planned to
      establish the place of this new alternative treatment of BPH in the urologist's
      armamentarium.

PMID- 7529451
TI  - [Nature of the effects of omega-3-polyenic fatty acids on the development of
      acute inflammation in experimental animals].
AB  - Influence of dietary w-6 and w-3 polyunsaturated fatty acids (PUFA),
      monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA) on development
      of rat paw edema induced by dextran subplantar injection was studied. Female
      Wistar rats the initial weight 150-160 g were bed fo four weeks diets containing
      as lioid components 6% butter and 3% sunflower oil (w-6 PUFA-diet), 6% butter and
      3% fish oil (w-3 PUFA-diet), 6% butter and 3% olive oil (MUFA-diet) or butter
      (SFA-diet). One group of rats received a non-lipid diet. The development of rat
      paw edema was reduced under the w-3 PUFA-diet in comparison with the w-6 PUFA
      diet, but more intensive then under the non-lipid diet. No differences were
      detected in effects on inflammation induced w-3 PUFA-, MUFA-, and SFA-diets.

PMID- 7529448
TI  - Do prostate size and urinary flow rates predict health care-seeking behavior for
      urinary symptoms in men?
AB  - OBJECTIVES: To estimate the association between health care-seeking behavior for
      urinary dysfunction and clinical, physiologic, and anatomic measures of disease.
      METHODS: A randomly selected sample (n = 475) of men aged 40 to 79 years from
      Olmsted County, Minnesota, was administered a previously validated questionnaire
      that assessed the frequency of and bother associated with urinary symptoms and
      health care-seeking behavior in the past year. Peak urinary flow rates were
      measured with a standard urometer and prostatic volume was determined by
      transrectal ultrasound. RESULTS: Overall, 21 of the 475 men (4%) had seen a
      doctor in the past year for urinary symptoms. Men with moderate to severe
      symptoms (American Urological Association [AUA] Symptom Scores > 7) were 3.4
      times as likely (95% confidence interval [CI] = 1.4, 8.3) to have sought medical
      care in the past year as men with none to mild symptoms. Men with enlarged
      prostates (> 40 mL) were 3.9 times as likely to have sought health care (95% CI =
      1.6, 9.6), whereas men with depressed peak urine flow rates (< 10 mL/s) were only
      slightly more likely to have sought health care for urinary symptoms (odds ratio
      = 2.1, 95% CI = 0.7, 6.5). Overall, 76% of men who had sought medical care had
      prostatic enlargement, depressed peak urine flow rates, or moderate-severe
      symptoms (sensitivity). In contrast, only 55% of men who did not seek health care
      for urinary symptoms in the past year had mild symptoms, normal prostatic volume,
      and normal peak urine flow rates (specificity). CONCLUSIONS: These data suggest
      that clinical, physiologic, and anatomic measures of prostatism do not adequately
      distinguish the men who seek medical care for their urinary symptoms from those
      who do not. There remain some factor(s) that apparently lead some men with minor
      disease to seek care and that prevent men with measurable disease from seeking
      care.

PMID- 7529450
TI  - Prediction of prostate cancer volume using prostate-specific antigen levels,
      transrectal ultrasound, and systematic sextant biopsies.
AB  - OBJECTIVES: Prostate-specific antigen (PSA) levels, transrectal ultrasound, and
      systematic sextant biopsies have each shown limited ability to predict prostate
      cancer volume. In combination, these studies may allow more accurate estimation
      of volume and prognosis. METHODS: One hundred twenty-four patients were evaluated
      prior to radical prostatectomy. Interactive stepwise multiple regression and
      separate logistic regression analysis were performed for prediction of prostate
      cancer volume and volume range. RESULTS: The cancer volumes calculated correlated
      with the volumes in the radical prostatectomy specimens with R2 of 0.76. Cancers
      were predicted to be in the volume range associated with poor prognosis (more
      than 12 cc) or clinically insignificant cancer (less than 1.0 cc) with bias
      corrected error rates of 5.3% and 10%, respectively. CONCLUSIONS: The formula for
      prediction of cancer volume correlates well with actual cancer volume in 92
      patients but is not adequate to predict volume for an individual patient. The
      formulas for prediction of volume range show promising predictive ability and may
      be useful if the extent of disease is unclear.

PMID- 7529452
TI  - Bone pain and radionuclide therapy.
AB  - The Council on Scientific Affairs of the California Medical Association presents
      the following epitomes of progress in nuclear medicine. Each item, in the
      judgment of a panel of knowledgeable physicians, has recently become reasonably
      firmly established, both as to scientific fact and clinical importance. The items
      are presented in simple epitome, and an authoritative reference, both to the item
      itself and to the subject as a whole, is generally given for those who may be
      unfamiliar with a particular item. The purpose is to assist busy practitioners,
      students, researchers, and scholars to stay abreast of progress in medicine,
      whether in their own field of special interest or another. The epitomes included
      here were selected by the Advisory Panel to the Section on Nuclear Medicine of
      the California Medical Association, and the summaries were prepared under the
      direction of Dr Lyons and the panel.

PMID- 7529449
TI  - Interexaminer variability of digital rectal examination in detecting prostate
      cancer.
AB  - OBJECTIVES: Digital rectal examination (DRE) is an important method of prostate
      cancer detection used by primary care physicians and medical specialists to
      identify patients in whom a prostatic biopsy is warranted. However, there is
      little empirical evidence assessing the degree of interexaminer variability in
      the use of DRE for the detection of prostate cancer. We addressed this issue
      within the framework of a prostate cancer screening study. METHODS: We performed
      DRE examinations in 116 consecutive volunteers twice on the same day, with
      different urologists performing the examinations. The urologists were blinded to
      the results of the other examination and to the subject's serum prostate-specific
      antigen (PSA) level. DRE results were coded as being benign or sufficiently
      suspicious for cancer to warrant a prostatic biopsy. RESULTS: Examiners
      independently agreed on the DRE findings in 98 of the 116 (84%) subjects.
      However, when adjusted for chance agreement, the interexaminer agreement among
      urologists was only fair (ie, kappa = 0.22, P = 0.009). Interexaminer variability
      was greater between faculty and resident examiners than among faculty examiners.
      CONCLUSIONS: Our results suggest that the reproducibility of DRE for detecting
      prostate cancer is only fair among urologists. Further studies are indicated to
      evaluate interexaminer variability between primary care physicians and
      urologists.

PMID- 7529453
TI  - Rochalimaea--a cosmopolitan zoonosis?

PMID- 7529454
TI  - A mortality study of lung cancer among swiss professional drivers: accounting for
      the smoking related fraction by a multivariate approach.
AB  - The mortality due to lung cancer among 'chauffeurs', who have a presumably long
      term exposure to diesel exhaust fumes, was analysed. As controls, men in
      industrial occupations of similar socio-economic status were selected. Cases were
      drawn from the Swiss mortality register for the years 1979-1983. Person-years
      were obtained using data from the 1980 census records. These two data files were
      combined by occupation, age class and socio-economic status. Age adjusted
      incidence rates were calculated applying Poisson regression. To control for
      tobacco related lung cancer mortality an indirect adjustment was undertaken.
      Using information about the smoking habits of the people in the occupations under
      study, smoking-attributable lung cancer mortality was accounted for by
      incorporating Axelson's technique into multivariate regression modeling. The
      mortality ratio for lung cancer for chauffeurs with respect to the controls was
      2.27, which is significantly in excess of 1:95% CI (1.99, 2.58). Other tobacco
      related diagnoses such as bladder cancer, esophageal cancer and ischemic heart
      diseases showed excess risks as well. After accounting for smoking, a slight but
      significant increase in lung cancer mortality remained among chauffeurs
      (mortality ratio 1.48, 95% CI: 1.30, 1.68). In summary, the present results do
      support the hypothesis that diesel exhaust is a significant cause of lung cancer.

PMID- 7529455
TI  - Fetal globin stimulation during a short-term trial of erythropoietin in HbS/beta
      thalassemia patients.
AB  - Six sickle cell/beta-thalassemia patients (3 males and 3 females) were treated
      with 500 U/kg body weight human recombinant erythropoietin (h-rEPO) along with
      300 mg/day iron sulfate in two phases, for a period of 90 days. Fetal hemoglobin
      (HbF) was assayed every 2 weeks and the gamma-chain ratio at three successive
      intervals during the treatment. All patients showed a moderate to high increase
      in their HbF values (1.25- to 12-fold). The gamma-chain ratio, as determined by
      high performance liquid chromatography was found to be unaffected by the HbF
      increase. Two patients with the newborn gamma-chain ratio, responded faster to
      the h-rEPO treatment and achieved higher HbF values than the rest of the group.
      The h-rEPO treatment was very well tolerated and had a positive effect on the
      general clinical condition of all the patients.

PMID- 7529456
TI  - The carbohydrate epitope 3-fucosyl-N-acetyllactosamine is region-specifically
      expressed in astrocytes of the rat brain. Light- and electron-microscopical
      observations.
AB  - The carbohydrate epitope 3-fucosyl-N-acetyllactosamine (CD15) is involved in cell
      to-cell recognition processes in various tissues. In the CNS of the adult rat,
      immunoreactivity for CD15 reveals a region-specific distribution pattern by light
      microscopy. In the present study we investigated the ultrastructural localization
      of CD15 in the rat brain using preembedding immunocytochemical methods. In
      addition we studied CD15 expression in cultured astrocytes from optic nerves of
      11-day-old rats. In optic nerve sections, immunostaining was found on the surface
      of astrocytes at various contact sites, i.e. astrocyte-astrocyte, astrocyte
      oligodendrocyte, astrocyte-axon myelin, and astrocyte-blood vessel contacts.
      Oligodendrocyte-oligodendrocyte contacts, however, were always negative. In the
      telencephalic cortex, CD15 immunoreactivity was found in glial cell processes
      around synapses and in the cerebellar cortex in Bergmann glial cells. In
      astrocytes grown in serum-containing medium, CD15 was expressed on the surface of
      fibroblast-like glial fibrillary acidic protein-positive astrocytes, which were
      identified as type 1 astrocytes as well as on process-bearing A2B5-positive
      cells, representing type 2 astrocytes. The present data support the assumption
      that in the adult rodent brain, CD15 is exclusively expressed by astrocytes. The
      in vivo distribution of this carbohydrate molecule on distinct astroglial contact
      sites supports the notion that CD15 could act in cell-to-cell recognition
      processes.

PMID- 7529458
TI  - The survival of cultured mouse cerebellar granule cells is not dependent on
      elevated potassium-ion concentration.
AB  - The effects of K(+)-induced membrane depolarization were studied on the survival
      and biochemical parameters in mouse and rat cerebellar granule cells grown in
      micro-well cultures. Cell numbers were determined by estimating DNA content using
      the Hoechst 33258 fluorochrome binding assay. DNA from degenerated cells was
      removed by prior DNAase treatment. These DNA estimates of cell numbers were
      comparable with values obtained by direct counting of fluorescein diacetate
      stained viable cells. In agreement with previous studies, the survival of rat
      granule cells was promoted by increasing the concentration of K+ in the medium
      from 5 to 25 mM throughout a 7-day culture period. In contrast, mouse granule
      cells survived in culture containing 'low' K+ (5 or 10 mM), as well as in the
      presence of 'high' K+ (25 mM). On the other hand, several biochemical parameters
      in mouse granule cells were markedly increased by cultivation in 'high' as
      compared with 'low' K(+)-containing media, demonstrated by increased fluorescein
      diacetate esterase activity, enhanced rate of NADPH-dependent tetrazolium
      reduction, augmented 2-deoxy-D-glucose accumulation and increased N-methyl-D
      aspartate-evoked 45Ca2+ influx. It was concluded that although cultivation in
      'high' K+ promotes biochemical differentiation in mouse cerebellar granule cells,
      these cells differ from their rat counterparts in that they do not develop a
      survival requirement for K(+)-induced membrane depolarization.

PMID- 7529457
TI  - Disturbed zinc metabolism and reduced birthweight related to raised maternal
      serum alpha-fetoprotein in normal human pregnancies.
AB  - The hypothesis was examined that altered maternal zinc metabolism is involved in
      the low birthweight associated with raised maternal serum alpha-fetoprotein
      (MSAFP). Mothers with clinically normal pregnancy and normally formed infant but
      with raised MSAFP (> 90th percentile) had lower than normal plasma zinc
      concentration, raised leucocyte zinc and disturbed zinc-albumin relationship.
      They delivered offspring with lower birthweights than did women with normal MSAFP
      concentration, due both to shorter pregnancy and slower intrauterine growth.
      These results and others identify a subgroup of mothers associated with low
      infant birthweight, those with raised MSAFP, who have altered zinc distribution.

PMID- 7529460
TI  - Preparation and specificity of antibodies against coat proteins of broad bean
      stain virus.
AB  - Mouse polyclonal antibodies were prepared against broad bean stain virus (BBSV,
      Comovirus group) and its coat protein subunits, large (L) and small (S) protein.
      These subunits were less immunogenic than native virus. Antibodies against L
      protein (Anti-L) and native virus (Anti-BBSV) did not react in immunoblots with S
      protein, but Anti-BBSV antibody reacted with S protein in plate-trapped antigen
      ELISA. Anti-S antibodies did not react with the related red clover mottle
      comovirus (RCMV), but Anti-L and Anti-BBSV antibodies reacted with RCMV similarly
      to BBSV. We assume that all the linear epitopes of the BBSV S protein are hidden
      in the native virions and the antigenic similarity between BBSV and RCMV is based
      mainly on their common linear L-specific epitopes.

PMID- 7529461
TI  - The applicability of a Keratin-7 monoclonal antibody in routinely Papanicolaou
      stained cytologic specimens for the differential diagnosis of carcinomas.

PMID- 7529459
TI  - Effects of tiludronate on bone mass, structure, and turnover at the epiphyseal,
      primary, and secondary spongiosa in the proximal tibia of growing rats after
      sciatic neurectomy.
AB  - To evaluate the effects of tiludronate on the mass, structure, and turnover of
      cancellous bone regions in immobilized rat tibiae, we performed a 4 week dosing
      experiment. The right hindlimbs of 84 Sprague-Dawley rats (5 weeks old) wee
      neurectomized or sham operated. Animals were assigned to seven groups (n = 12
      each); group 1 was sham operated, and groups 2-7 were neurectomized. Groups 1 and
      2 were given vehicle only (distilled water), and groups 3, 4, and 5 were given
      tiludronate orally at doses of 25, 50, and 100 mg/kg body weight (BW)/day,
      respectively, throughout the experimental period. Group 6 was given 100 mg/kg
      BW/day of the agent for the first 2 weeks only, and group 7 received vehicle only
      for the first 2 weeks and then 100 mg/kg BW/day of the agent for the last 2
      weeks. After tetracycline labeling was performed, the right tibiae were removed
      from the animals and processed to yield undecalcified sections. Histomorphometry
      was performed in the epiphyseal, primary, and secondary spongiosa of the proximal
      tibia. In group 2, trabecular bone volume (BV/TV) and trabecular number (Tb.N)
      were significantly decreased in the primary and secondary spongiosae, but this
      did not occur in the epiphyseal spongiosa. Osteoid surface (OS/BS) was decreased
      and osteoclast surface (Oc.S/BS) was increased in the secondary spongiosa.
      Tiludronate increased BV/TV and Tb.N in the primary spongiosa by reducing the
      values for the parameters of osteoclast surface (Oc.S/BS) and osteoclast number
      (Oc.N/BS). Osteoid surface in this region was not decreased by the agent. In
      groups 4 and 5, tiludronate prevented bone loss in the secondary spongiosa by
      reducing both OS/BS and Oc.S/BS. In group 6, BV/TV in the primary spongiosa was
      maintained at the level of group 1, but Oc.S/BS and Oc.N/BS were elevated. In the
      secondary spongiosa, bone mass was preserved and the reduction in these
      parameters was maintained. In group 7, however, BV/TV was increased in the
      primary spongiosa as a result of a reduction in osteoclastic resorption; in the
      secondary spongiosa, however, BV/TV was decreased and trabecular turnover was not
      reduced at the end of the experiment in these growing animals. Mineral apposition
      rates were not reduced by tiludronate. This study clearly demonstrated that this
      agent prevented immobilization bone loss by inhibiting resorption.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7529462
TI  - Isovolemic hemodilution with dextran prevents contrast medium induced impairment
      of pancreatic microcirculation in necrotizing pancreatitis of the rat.
AB  - BACKGROUND: Previous studies demonstrated that intravenous contrast medium (CM),
      as used in contrast enhanced computed tomography, aggravates the impairment of
      pancreatic microcirculation (PM) characteristic of severe pancreatitis and
      increases necrosis and mortality in necrotizing pancreatitis (NP) in rats. This
      study evaluates the use of isovolemic hemodilution, which can enhance the
      microcirculation in severe pancreatitis, for preventing CM-induced injury.
      METHODS: NP was induced in 30 dextran-tolerant Wistar rats by intraductal
      glycodeoxycholic acid and intravenous cerulein for 6 hours. PM was quantified by
      intravital microscopy using fluorescein isothiocyanate labeled erythrocytes.
      Based on previous results, areas with low blood flow (< 1.6 nL/min/cap) were
      identified and baseline recordings of capillary blood flow taken. A reduction of
      hematocrit to 75% of baseline was achieved by replacement of 5 mL/kg of blood
      with 25 mL/kg Ringer's lactate (RL) or by exchange of 8 mL/kg of blood for the
      same amount of dextran 70.6%. Thereafter, the nonionic CM iopamidol (Solutrast,
      Byk Gulden, Konstanz, Germany) was injected during 1 minute and PM measurements
      repeated after 30 and 60 minutes. RESULTS: Despite hemodilution with RL,
      pancreatic capillary perfusion was significantly decreased to 87% of baseline
      (0.83 +/- 0.04 mL/min/cap; n = 216) 60 minutes after CM infusion (P < 0.05). In
      contrast, capillary blood flow was significantly increased to 161% (1.56 +/- 0.05
      nL/min/cap; n = 278) in the group treated with dextran. Moreover, the percentage
      of capillaries developing complete stasis was significantly lower in the dextran
      group (2.3 +/- 1.2%) compared to animals diluted with RL (22.3 +/- 4.8%) (P <
      0.002). CONCLUSION: Isovolemic hemodilution with dextran prevents the additional
      impairment of pancreatic microcirculation induced by CM in NP.

PMID- 7529463
TI  - [Zinc and health].

PMID- 7529464
TI  - High-dose aprotinin in cardiac surgery--a prospective, randomized study.
AB  - Fifty patients undergoing primary coronary artery bypass surgery and 50 patients
      undergoing valve surgery received either high-dose aprotinin (2 million units
      loading dose, 2 million units added to the CPB prime, and 500,000 units/hr
      maintenance infusion) or placebo. Mean postoperative blood loss in the first six
      hours was reduced from 321 ml in the placebo group to 172 ml in the aprotinin
      group (95% confidence interval (CI) for difference = 95 to 189 ml). Seven
      patients in the placebo group and 16 patients in the aprotinin group did not
      require transfusion with homologous blood. This study adds to the growing body of
      evidence that the administration of high-dose aprotinin reduces blood loss and
      blood transfusion requirements associated with primary cardiac surgery.

PMID- 7529466
TI  - The fate of somitocoele cells in avian embryos.
AB  - The early somite of avian embryos is made up of an epithelial wall and
      mesenchymal cells located within the somitocoele. We have studied the fate of
      somitocoele cells for a period of up to 6 days, using the quail-chick marker
      technique. We also applied the QH-1 antibody, which specifically stains
      hemangiopoietic cells of quail origin, and studied the proliferative activity of
      epithelial somites with the BrdU anti-BrdU method. Our results show that
      somitocoele cells mainly give rise to the ribs and peripheral parts of the
      intervertebral discs. After 1 and 2 days of reincubation, the grafted somitocoele
      cells were located in the lateral part of the sclerotome, and only a few cells
      migrated axially towards the notochord. In frontal sections, the cells were
      located in a triangular area within the cranial part of the caudal sclerotome
      half. After 3 days of reincubation, some of the cells had migrated cranially
      along the myotome. After longer reincubation periods, cells grafted into one
      somite could be found in two adjacent ribs. The studies with the QH-1 antibody
      show that a subpopulation of somitocoele cells has angiogenic potency.
      Endothelial cells originating from the mesenchyme of the somitocoele migrated
      actively and even invaded the ipsilateral half of the neural tube. In the
      epithelial wall of the somite, BrdU-labelled nuclei were found basally, whereas
      more apically the nuclei were not stained, but mitotic figures were frequently
      present. The somitocoele cells also showed a high proliferative activity with
      about 26% of nuclei labelled with BrdU.

PMID- 7529467
TI  - Aprotinin decreases blood loss in patients undergoing revision or bilateral total
      hip arthroplasty.
AB  - Two recent studies have shown decreased blood loss in patients given aprotinin
      undergoing primary hip replacement surgery. Because patients undergoing bilateral
      (bTHA) or revision total hip arthroplasty (rTHA) suffer more blood loss than
      those undergoing primary THA, we studied consecutive patients undergoing bTHA or
      rTHA who were randomized to receive either a blinded solution of 3.8 x 10(6)
      Kallikrein inactivation units (KIU) aprotinin (n = 29) or placebo (n = 24)
      throughout the surgical procedure. Total blood loss, measured as intraoperative
      suction losses, weight of sponges, and postoperative volumetric drainage, was
      compared between groups. Aprotinin patients had significantly less total blood
      loss 1498 +/- 110 mL (mean +/- SEM) versus 2096 +/- 223 (P = 0.022), and
      transfused patients in the aprotinin group received fewer packed red blood cells
      than placebo-treated patients (confidence interval for the difference -1.69, 
      0.07). In addition, assessment of biochemical markers of hepatic and renal
      function did not disclose any clinically important differences between groups.
      Patients were also assessed for development of deep venous thrombosis (DVT) by
      preoperative and predischarge bilateral lower limb compression ultrasound. None
      of the aprotinin-treated patients and three placebo-treated patients demonstrated
      DVT. Unless this trend for decreased DVT with aprotinin can be confirmed, it is
      questionable whether the slight reduction in blood loss justifies routine use of
      this expensive drug.

PMID- 7529465
TI  - Rostro-caudal polarity in the avian somite related to paraxial segmentation. A
      study on HNK-1, tenascin and neurofilament expression.
AB  - Segmental organization of the vertebrate body is one of the major patterns
      arising during embryonic development. Somites that play an important role in this
      process show intrinsic patterns of gene expression and differentiation. The
      somites become polarized in all three dimensions, rostrocaudal, mediolateral and
      dorsoventral, the quadrants giving rise to several tissue components. The timing
      of polarization was studied by means of antibodies against HNK-1, tenascin and
      neurofilament. Whole mounts and serial sections of quail and chick embryos show
      that somites are already polarized at the moment of their segregation from the
      segmental plate. The rostral hemisomite carries the HNK-1 epitope preferentially,
      while the caudal hemisomite stains more strongly for tenascin. HNK-1-stained
      areas in the segmental plate strongly relate to the notochordal sheath,
      suggesting that axial structures determine the fate of paraxial structures.
      Neural crest cells were only seen to colonize the rostral part of a somite after
      they had differentiated into HNK-1 positive cells. Their colonization pattern
      seems to be guided by the segmental organization of the somite. Moreover, this
      somite organization probably dictates the organization of both sensory and motor
      fibres converging towards the segmental dorsal root ganglia, justifying a shift
      in the connections between neural tube and somites. This segmental shift takes
      place over one quarter of a somite length in a rostral direction.

PMID- 7529470
TI  - A polymorphic microsatellite detected in the ovine CD5 gene.

PMID- 7529469
TI  - A MspI RFLP at the chicken tyrosine hydroxylase locus (TH).

PMID- 7529468
TI  - Comparative effects of small and large aprotinin doses on bleeding during
      orthotopic liver transplantation.
AB  - Large prophylactic doses of aprotinin efficiently reduce blood loss during
      orthotopic liver transplantation (OLT). Small doses of aprotinin are usually used
      to treat fibrinolysis. However, no studies have investigated the benefit of
      prophylactic administration of a smaller dose of aprotinin during liver
      transplantation. We compared two methods of aprotinin therapy on transfusion
      outcome in liver transplant patients in a prospective study of 199 patients
      undergoing OLT who were randomized to large or small prophylactic doses of
      aprotinin during the transplant procedure. In the large-dose group (n = 94) an
      initial dose of 2,000,000 kallikrein inactivation units (KIU) was followed by
      infusion of 500,000 KIU/h until the patient's return to the intensive care unit.
      In the small-dose group (n = 95), an initial dose of 500,000 KIU was followed by
      an infusion of 150,000 KIU/h. Outcome measurements included intraoperative
      transfusion requirements (packed red blood cells, fresh frozen plasma, platelets,
      intraoperative salvage) and postoperative hematologic values. There were no
      differences in transfusion requirements in the two groups of patients. Patients
      treated with low-dose aprotinin had slightly higher postoperative fibrinogen
      concentrations. Large-dose aprotinin therapy does not appear to offer additional
      benefit compared to low-dose aprotinin administration.

PMID- 7529473
TI  - Neonatal alloimmune thrombocytopenia: current considerations.
AB  - Some mothers produce antibodies to the platelet antigens of their fetuses.
      Exposure to these antigens may occur owing to prior transfusions or through feto
      maternal hemorrhage during gestation or delivery. The sensitizing antigen is
      usually an epitope of one of the glycoproteins (GP) found on the platelet
      membrane. Specific GPs act as receptors for factors important in hemostasis, such
      as von Willebrand's Factor (vWF), fibrinogen, fibronectin, and collagen.
      Molecular biological techniques have identified single base pair substitutions
      resulting in antigenic specificity owing to one amino acid difference in a
      particular GP. Human platelet antigen (HPA) 1a is the most antigenic of the GPs.
      Neonatal alloimmune thrombocytopenia (NAT) results when a mother lacking an
      antigen present on fetal platelets develops the specific antibody. The incidence
      of NAT ranges from 1/1,500 to 1/5,000 births. An affected child is born with
      thrombocytopenia and may suffer consequences varying from petechiae and minor
      bleeding to central nervous system hemorrhage and death. Approximately 50 percent
      of the time, NAT is evident with the first pregnancy. Recent advances in
      obstetrical care permit percutaneous umbilical blood sampling (PUBS) early in
      pregnancy to determine whether or not the fetus is being adversely affected.
      Treatment through the use of cordocentesis and infusion of the mother's platelets
      or other compatible platelets may be performed. Clear identification of
      antibodies against platelets remains problematic for the routine clinical
      laboratory. Reagents to identify platelet antigens and antibodies are not readily
      available. Postnatal treatment of NAT requires infusion of the mother's platelets
      or platelets which are antigenetically compatible with the mother.

PMID- 7529471
TI  - A MspI polymorphism at the albumin (ALB) locus in cattle.

PMID- 7529472
TI  - Rapid quantitation of hemoglobin S by isoelectric focusing.
AB  - The feasibility of isoelectric focusing (IEF) to determine hemoglobin S (HbS) at
      a faster turn-around-time and to resolve the HbS and hemoglobin A (HbA) in
      presence of high concentrations of hemoglobin F (HbF) is evaluated. The IEF
      procedure is faster, and the results can be obtained in less than 45 minutes. The
      resulting data are comparable to gel electrophoresis. It is a superior procedure
      in resolving both HbS and HbA in the presence of high HbF and, therefore, a
      desirable technique to use for infants and children. Further, IEF is simpler than
      the gel electrophoresis, relatively inexpensive, easily adaptable for routine
      use, and suitable for "stat" conditions.

PMID- 7529474
TI  - Neuroprotective effects of gangliosides may involve inhibition of nitric oxide
      synthase.
AB  - Gangliosides are polar, sugar-containing lipids that are major constituents of
      neuronal membranes. Gangliosides are neuroprotective in animal models of
      neurotoxicity and may also be useful in patients with clinical conditions such as
      spinal cord injury. We show that a series of gangliosides inhibit nitric oxide
      synthase activity by binding calmodulin. The prevention of glutamate
      neurotoxicity in cortical cultures by gangliosides closely parallels their
      potencies in binding calmodulin and inhibiting nitric oxide synthase.
      Neuroprotective effects of gangliosides may arise from blockade of nitric oxide
      formation.

PMID- 7529476
TI  - The interferons: biological effects, mechanisms of action, and use in multiple
      sclerosis.

PMID- 7529475
TI  - Circulating, soluble adhesion proteins in cerebrospinal fluid and serum of
      patients with multiple sclerosis: correlation with clinical activity.
AB  - Soluble adhesion protein intercellular adhesion molecule-1 (ICAM-1), vascular
      cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (E
      selectin) were measured in serum and cerebrospinal fluid (CSF) of patients with
      relapsing-remitting multiple sclerosis (RRMS) in remission and in exacerbation,
      as well as patients with chronic progressive MS, stable MS, and in patients with
      other neurological and inflammatory diseases (ONDs). Serum ICAM-1 and E-selectin
      were significantly elevated in patients with MS over those with ONDs and
      controls. CSF VCAM-1 and E-selectin were found to be elevated over control and
      disease control samples. No increase in CSF ICAM-1 was observed. Results were
      analyzed longitudinally and by MS category. In paired CSF and serum samples from
      patients in exacerbation, elevated VCAM-1 correlated with increased serum VCAM-1
      in 5 of 7 patients. Elevated CSF E-selectin did not correlate with elevations in
      serum E-selectin.

PMID- 7529478
TI  - Poster sessions tips for the novice viewer.

PMID- 7529477
TI  - Activation and stabilization of enzymes entrapped into reversed micelles. Studies
      on hydrolyzing enzymes--protease and alpha-amylase.
AB  - Observations of the activity of two hydrolyzing enzymes-protease and alpha
      amylase--entrapped inside the reversed micelles formed by surfactants in hexane,
      benzene, and cyclohexane are reported. The surfactants chosen for this study are:
      Tween 80, a nonionic surfactant, Cetyl pyridinium chloride, a cationic
      surfactant, and two anionic surfactants, sodium lauryl sulfate and Aerosol OT.
      Tween 80 enhances the activity of both protease and alpha-amylase. Sodium lauryl
      sulfate and Aerosol OT, which are ionic surfactants, enhance the activity of
      protease, but inhibit the activity of alpha-amylase. Cetyl pyridinium chloride,
      however, enhances the activity of alpha-amylase, but inhibits the activity of
      protease. Enhanced activity is generally severalfold greater in comparison to the
      activity observed in the usual aqueous system in the absence of reversed
      micelles. It has also been observed that the enhanced activity of the enzymes
      entrapped inside the reversed micelles remains preserved for a much longer period
      of time in comparison to the activity in the usual aqueous systems. These
      observations, which support the view that with proper choice of surfactant and
      the organic solvent, reversed micelles act like a microreactor that provides a
      favorable aqueous micro-environment for enzyme activity, have biotechnological
      overtones.

PMID- 7529479
TI  - Phenotypic evaluation of cultured human mast and basophilic cells and of normal
      human skin mast cells.
AB  - In order to evaluate various markers for human mast cells, two human
      mast/basophilic cell lines (HMC-1/KU812), cultured mast cells from the peripheral
      blood monocytic fraction and peripheral blood monocytes were compared with mast
      cells in tissue sections from normal skin, using histochemistry, enzyme
      histochemistry and immunohistochemistry. All reagents stained normal skin mast
      cells, with toluidine blue, tryptase reactivity and antibodies against the Fc
      epsilon RI and the stem cell factor receptor (c-kit) being most active. The cell
      lines and mast cells cultured from peripheral blood were negative for avidin,
      safranin and chymase, strongly positive for c-kit and variably reactive with all
      other reagents. All antibodies except AA1 against tryptase also stained one or
      several epidermal and dermal cell types or blood monocytes. Histochemical stains
      (toluidine blue, avidin) and reagents for the enzymes tryptase and chymase are
      thus specific markers for mast cells. The frequent reactivity of antibodies
      against mast cells with other cell types indicates interesting functional and
      ontogenetic relationships between these cells.

PMID- 7529483
TI  - Effect of aprotinin on activated clotting time, whole blood and plasma heparin
      measurements.
AB  - Twenty cardiac surgical patients requiring cardiopulmonary bypass were enrolled
      in this study designed to evaluate the effect of aprotinin on activated clotting
      time (kaolin and celite), whole blood, and laboratory-based plasma (anti-Xa)
      heparin measurements. Whole blood heparin measurements were not different (p =
      0.98) between aprotinin-treated (3.2 +/- 2.8 U/mL) and control (3.2 +/- 3.0 U/mL)
      specimens. Plasma anti-Xa heparin measurements were also not different (p = 0.95)
      between aprotinin-treated (2.7 +/- 2.5 U/mL) and control (2.8 +/- 2.5 U/mL)
      specimens. The relationship between whole blood (plasma equivalent) and plasma
      heparin measurements was similar (p = 0.1) in the presence (slope, 1.04; r2 =
      0.89) or absence (slope, 1.11; r2 = 0.89) of aprotinin. In contrast to weak
      correlations between celite (r = 0.50) or kaolin (r = 0.53) activated clotting
      time values, whole blood heparin measurements correlated well (r = 0.93) with
      plasma heparin measurements during cardiopulmonary bypass in the presence of
      aprotinin. These findings indicate that whole blood heparin measurements are
      unaffected by aprotinin and correlate well with plasma anti-Xa heparin
      measurements even in the presence of aprotinin. Therefore, the automated
      protamine titration assay can be used to monitor accurately heparin
      concentrations in patients receiving aprotinin.

PMID- 7529480
TI  - Distribution of apoptosis-mediating Fas antigen in human skin and effects of anti
      Fas monoclonal antibody on human epidermal keratinocyte and squamous cell
      carcinoma cell lines.
AB  - Fast antigen is a cell surface protein that mediates apoptosis. Using
      immunohistological, flow cytometry and electron microscopic analyses, we
      investigated the expression of Fas antigen on various skin tissues, and on
      cultured SV40-transformed human epidermal keratinocyte cell line KJD and human
      skin squamous cell carcinoma cell line HSC. The Fas antigen was widely
      distributed in skin components such as the keratinocytes in the lower portion of
      the epidermis, epidermal dendritic cells, endothelial cells, fibroblasts,
      apocrine glands, eccrine sweat glands, sebaceous glands, some normal melanocytes
      and infiltrating lymphoid cells. It was also strongly expressed on the
      keratinocytes of lichenoid eruptions seen in lupus erythematosus and lichen
      planus, and on the spongiotic or acanthotic epidermis seen in chronic eczema,
      adult T-cell leukaemia/lymphoma (ATLL) and atopic dermatitis. Its expression was
      closely correlated with lymphoid infiltrating cells and it was strongly expressed
      in lymphoid neoplastic cells, particularly ATLL cells, and fibroblasts seen in
      dermatofibroma. However, the antigen was not detected on basal cell epithelioma
      cells, some malignant melanomas or any junctional naevi. The cell lines KJD and
      HSC strongly expressed the Fas antigen, and crosslinking of the Fas antigen by an
      anti-Fas monoclonal antibody induced apoptosis of these cell lines. These results
      indicate that the apoptosis-mediating Fas antigen may play an important role in
      normal skin turnover and cell differentiation, in immune regulation of skin
      tumours, and in the pathogenesis of various skin diseases.

PMID- 7529482
TI  - Circulating adhesion molecules in cardiac operations: influence of high-dose
      aprotinin.
AB  - Cardiac operations using cardiopulmonary bypass (CPB) are associated with a
      systemic inflammatory response most likely attributable to the release of various
      inflammatory mediators and activation of complement or coagulation cascade. In
      addition, (circulating) adhesion molecules, such as endothelial leukocyte
      adhesion molecule (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and
      intercellular adhesion molecule-1 (ICAM-1), appear to be of central importance in
      the CPB-related inflammatory process. In this situation, antiproteases, such as
      aprotinin, may help to prevent damage of endothelial integrity. In a prospective
      study, 40 consecutive patients undergoing elective cardiac operation were
      randomly divided into two groups (with 20 patients in each group): in group 1
      "high-dose" aprotinin was used (2 million IU of aprotinin before CPB, 500,000
      IU/h until end of operation, 2 million IU added to the prime) (with aprotinin),
      and in group 2 no aprotinin was given (without aprotinin). Circulating adhesion
      molecules (cICAM-1, cELAM-1, and cVCAM-1) were measured from arterial blood
      samples using ELISA after induction of anesthesia (baseline), during CPB, at the
      end of the operation, 5 hours after CPB, and on the first postoperative day. The
      two groups were comparable concerning their biometric profile and CPB data.
      Baseline values of circulating adhesion molecules were within normal range and
      similar in both groups. During CPB, hemodilution resulted in a decrease in all
      circulating adhesion molecules. On the first postoperative day, cICAM-1 (with
      aprotinin, 215 +/- 32 ng/mL; without aprotinin, 230 +/- 40 ng/mL) and cELAM-1
      (with aprotinin, 28 +/- 6 ng/mL; without aprotinin, 31 +/- 6 ng/mL) returned to
      baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529484
TI  - Aprotinin for coronary artery bypass grafting: effect on postoperative renal
      function.
AB  - Two hundred sixteen patients undergoing coronary artery bypass graft procedures
      were randomized to receive either high-dose aprotinin or placebo. Clinically
      important postoperative renal insufficiency was infrequent, with a single patient
      (0.9%) from each group requiring dialysis. Although increases in the serum
      creatinine level occurred postoperatively in more patients who received aprotinin
      (20/108) than in those given placebo (13/108), the difference between the two
      groups was not statistically significant (p = 0.186), and the increases were
      generally small and transient. Likewise, there was no difference between the
      groups in terms of the incidence of abnormal serum electrolyte levels, blood urea
      nitrogen levels, or urinalysis findings, or in the frequency of abnormal
      creatinine clearance rates. Under the conditions described, aprotinin use does
      not appear to be associated with a significant risk of serious renal toxicity.

PMID- 7529481
TI  - Elevated serum-soluble ELAM-1 levels in patients with severe plaque-type
      psoriasis.

PMID- 7529485
TI  - Iloprost and echistatin protect platelets during simulated extracorporeal
      circulation.
AB  - Temporary, reversible inhibition of platelets during cardiopulmonary bypass is an
      attractive strategy to protect platelets and normalize postoperative bleeding
      times. Iloprost, an analogue of prostacyclin, and the disintegrins reversibly
      inhibit platelets by different mechanisms. We tested the hypothesis that reduced
      doses of iloprost and either echistatin, a natural disintegrin, or RO43-5054, a
      peptidomimetic, in combination provide better platelet protection than any drug
      alone during simulated extracorporeal circulation. Thirty-five recirculation
      studies using fresh, heparinized human blood in an extracorporeal perfusion
      circuit that contained a 0.45-m2 spiral coil membrane oxygenator were performed.
      Iloprost, but neither echistatin nor RO43-5054, increased platelet cyclic
      adenosine monophosphate. Combinations of iloprost and either fibrinogen receptor
      antagonist at reduced doses submaximally increased platelet cyclic adenosine
      monophosphate. Platelet adhesion and release of beta-thromboglobulin antigen was
      completely inhibited by combinations of the two classes of drugs, but only
      partially inhibited by each drug alone. Combinations of drugs also completely
      inhibited platelet aggregation to adenosine diphosphate; these platelets retained
      full sensitivity to adenosine diphosphate after 90 minutes of recirculation when
      drugs were removed by gel filtration. We conclude that combinations of iloprost
      and a fibrinogen receptor antagonist at doses that are unlikely to produce
      clinical side effects completely inhibit platelet activation and preserve
      platelet function during in vitro extracorporeal circulation.

PMID- 7529487
TI  - Anastomotic pseudoaneurysm of the ventricle after homograft placement in
      children.
AB  - A pseudoaneurysm of the right ventricle was diagnosed postoperatively in 8
      patients between 1986 and 1992. One pseudoaneurysm formed after placement of a
      Carpentier-Edwards conduit and the other seven arose after placement of a
      homograft between the right ventricle and the pulmonary artery. Both aortic (n =
      3) and pulmonary (n = 4) homografts had been used. In 6 patients, the homografts
      had been augmented proximally with Dacron, Gore-Tex, or pericardium.
      Pseudoaneurysms originated between the augmentation patch and the homograft in 4
      patients, between the homograft or conduit and the myocardium in 3 patients (1
      patient with and 2 without an augmentation patch), and between the patch and the
      myocardium in 1 patient. The prior operations performed were placement of a
      palliative conduit for tetralogy of Fallot with pulmonary atresia (n = 5), repair
      of truncus arteriosus (n = 2), and repair of absent pulmonary valve syndrome (n =
      1). Pseudoaneurysms were discovered from 5 weeks to 4 years after the operation.
      Symptoms were present in 3 patients; in the others, diagnosis was made during
      follow-up on the basis of routine imaging studies. Symptoms, when present, were
      due to compression of surrounding mediastinal structures. Pseudoaneurysms ranged
      in diameter from 1.0 to 5.0 cm. Echocardiography and color-flow mapping reliably
      identified the pseudoaneurysm in the 6 patients in whom it was performed.
      Characteristic features included a well-defined, narrow aneurysm neck leading to
      an extracardiac echo-free space. Color-flow mapping demonstrated to-and-fro flow
      through the neck of the aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529486
TI  - Can esophagectomy cure cancer of the thoracic esophagus involving the major
      airways?
AB  - To evaluate the effects of aggressive operation for esophageal cancer invading
      the trachea and main bronchi, we investigated retrospectively 62 patients with
      proven tracheobronchial involvement who underwent thoracotomy for esophagectomy
      between 1973 and 1993. We operated unless the tumor was assessed to be definitely
      unresectable. Esophagectomy was possible in 55 patients, and the resectability
      rate was 95% after preoperative computed tomography and bronchoscopy became
      routine. After esophagectomy, no residual cancer lesion was recognizable
      macroscopically in 53% of patients. The hospital mortality rate in esophagectomy
      cases was 7% in the past 8 years. The outcome in patients who underwent curative
      resection was significantly favorable (p < 0.0001), and the 2-year survival was
      51%. The patients with nonresectable cancer all died within 6 months compared
      with a 23% 1-year survival rate for palliative esophagectomy cases (p < 0.006).
      Among patients with tracheobronchial involvement assessed as resectable on
      computed tomography and bronchoscopy, a considerable proportion benefited from
      aggressive therapy with esophagectomy. The possibility of complete cure was high,
      especially when the cancer responded well to preoperative therapy and no lymph
      nodes were involved.

PMID- 7529488
TI  - Sequence homology among sperm antigens involved in mammalian fertilization:
      search for a common epitope for immunocontraception.
AB  - Sequence homology was searched among the nine cDNAs/deduced amino acid sequences
      encoding for the eight fertilization-related sperm antigens: namely, lactate
      dehydrogenase (LDH-C4), galactosyltransferase (GT), SP-10, rabbit sperm
      autoantigen (RSA), guinea pig (g)PH-20, cleavage signal protein (CS-1), HSA-63,
      human (h)PH-20, and AgX-1, respectively. Most significant identity (> 50%) was
      found between HSA-63 and SP-10 (59.8%), and between gPH-20 and hPH-20 (61.1%);
      followed by identity between SP-10 and GT (34.7%); and then between AgX-1 and hPH
      20 (39.4%). All others had identity < 25%. The significance of these sequence
      homologies among the sperm antigens in the development of an antisperm
      contraceptive vaccine is discussed.

PMID- 7529489
TI  - The effect of finasteride on prostate volume, urinary flow rate and symptom score
      in men with benign prostatic hyperplasia.
AB  - This study was designed to determine the efficacy of the 5 alpha-reductase
      inhibitor finasteride (Proscar, MK-906) in men with reduced urinary flow rates
      and symptoms of urinary outflow obstruction secondary to benign prostatic
      hyperplasia. Forty-five men were randomized to one of three groups receiving
      either placebo, 1 mg/day or 5 mg/day finasteride for the first 12 months of the
      study period. At the end of this period all men received 5 mg/day finasteride for
      a further 2 years. Efficacy was determined by measurement of prostate volume,
      maximum urinary flow rate, and symptom score using a modified Boyarsky
      assessment. Prostate volume reduced by 20 and 27%, respectively, for those on 1
      and 5 mg after the first year. At 3 years the volume had reduced by 43%. This
      reduction in prostate volume was associated with an improvement in maximum
      urinary flow rate by 50% (1 mg), and 35% (5 mg) at 1 year, and 36% at 3 years.
      The total, obstructive and non-obstructive symptom scores decreased (improved)
      for patients on 1 and 5 mg finasteride, with the total score reducing by 33% from
      baseline at year 3. The results demonstrate that finasteride causes a modest but
      significant clinical improvement in men with urinary outflow obstruction
      secondary to benign prostatic hyperplasia.

PMID- 7529490
TI  - Further evaluation of transurethral laser ablation of the prostate in patients
      treated with anticoagulant therapy.
AB  - Transurethral Nd:YAG laser ablation of the prostate gland was used to treat
      benign prostatic hyperplasia (BPH) in 20 patients on Warfarin anticoagulant
      therapy, and in two patients with abnormal coagulation parameters secondary to
      haematologic disorders. Preliminary results for the first 10 of these patients
      has been reported previously. The mean pre-operative international normalized
      ratio (INR) was 2.6 (range 1.19 to 5.25) and the mean prostate volume was 56 cc
      (13.6-112 cc). All patients had significant subjective and objective indicators
      of prostatic obstruction and six patients were in urinary retention.
      Postoperative improvement in symptom score, maximum flow rate and post-void
      residual was noted in 82% of patients at 3 months, 89% at 6 months and 75% at 1
      year. Two patients have required revision laser or transurethral resection of the
      prostate (TURP) for persistent obstruction, while one patient required revision
      TURP for intractable haematuria. Three patients developed haematuria requiring
      transfusion while four patients had mild haematuria requiring no intervention.
      Laser ablation of the prostate can be used successfully and safely to treat
      prostatic obstruction in patients with abnormal coagulation parameters, or in
      those who are fully anticoagulated. Anticoagulation can be maintained during
      surgery in this group unlike TURP where pre-operative reversal is necessary with
      reinstitution of therapy several days postoperatively. Other authors report at
      least a 50% blood transfusion rate in this group. Laser prostatectomy appears the
      more appealing surgical option in these patients.

PMID- 7529491
TI  - Expression of rat brain nitric oxide synthase in baculovirus-infected insect
      cells and characterization of the purified enzyme.
AB  - Rat brain nitric oxide synthase was expressed to a high level in baculovirus
      infected insect cells and purified to apparent homogeneity by affinity
      chromatography. The enzyme had a specific activity of approximately 1 mumol of
      citrulline.min-1.mg of protein-1 and contained 0.93, 0.45, 0.18 and 0.23 mol of
      haem, (6R)-5,6,7,8-tetrahydro-L-biopterin (H4biopterin), FAD and FMN per mol of
      subunit respectively.

PMID- 7529492
TI  - Identification of a human gastric mucin precursor: N-linked glycosylation and
      oligomerization.
AB  - Gastric mucin plays an important role in the protection of the stomach wall from
      chemical, microbiological and mechanical damage. We have previously isolated
      human gastric mucus glycoproteins and raised a polyclonal antiserum against these
      macromolecules. This antiserum specifically reacted with gastric mucins in
      immunoblotting experiments and stained mucous granules at the apical side of
      gastric surface epithelial cells. A similar staining pattern was obtained after
      incubation with an antiserum against rat gastric mucin. Next we used the
      antiserum in pulse-chase experiments of human stomach tissue explants. After
      short labelling periods with [35S]methionine and [35S]cysteine, the antiserum
      reacted with a polypeptide with an apparent molecular mass of approx. 500 kDa as
      determined by SDS/PAGE, which was converted after 90 min into a heterogeneous
      high-molecular-mass glycoprotein. This high-molecular-mass form, but not the 500
      kDa polypeptide, was detectable in the culture medium after 2 h. This strongly
      suggests that the 500 kDa polypeptide is the precursor of the purified gastric
      mucin. Analysis of pulse-chase experiments by non-reducing SDS/PAGE revealed that
      the precursors form disulphide-linked oligomers early in biosynthesis, before the
      addition of O-linked sugars. After preincubation with the N-glycosylation
      inhibitor, tunicamycin, the apparent molecular mass of the precursor decreased
      marginally but consistently, indicating that N-linked glycan chains are present
      on the mucin precursor.

PMID- 7529495
TI  - Interleukin-13 induces rapid tyrosine phosphorylation and activation of Raf-1
      kinase in human monocytic progenitor cell line U937.
AB  - IL-13 is a pleiotropic cytokine produced by Th0, Th1-like, and CD8 T cells in
      response to antigen stimulation. Its biological effects include suppression of
      cytotoxic activity of monocytes/macrophages and suppression of pro-inflammatory
      cytokine production. However, the mechanism of IL-13 remains unknown. In this
      study we investigated the effects of rhIL-13 on tyrosine phosphorylation in U937
      monocytic progenitor cells by immunoblotting and immunocomplex kinase assays. We
      demonstrate that rhIL-13 stimulates dose-dependent tyrosine phosphorylation of
      several proteins of Mr. 93, 80, 74, 49.5, 42, 30, 22 and 18 kDa within 30 sec.
      The effect of IL-13 was blocked by the tyrosine kinase inhibitor erbstatin.
      Furthermore, IL-13 induces tyrosine phosphorylation and rapid activation of raf-1
      kinase. These findings provide the first evidence that the mechanism of IL-13
      involves rapid tryrosine phosphorylation and activation of raf-1 serine/threonine
      kinase.

PMID- 7529494
TI  - Preferential antagonism of the interactions of the integrin alpha IIb beta 3 with
      immobilized glycoprotein ligands by snake-venom RGD (Arg-Gly-Asp) proteins.
      Evidence supporting a functional role for the amino acid residues flanking the
      tripeptide RGD in determining the inhibitory properties of snake-venom RGD
      proteins.
AB  - The inhibitory properties of a panel of snake-venom-derived RGD (Arg-Gly-Asp)
      proteins, including the disintegrins kistrin, elegantin and albolabrin, and the
      neurotoxin homologue dendroaspin, were investigated in a platelet-adhesion assay
      using three immobilized ligands of the glycoprotein IIb-IIIa complex (alpha IIb
      beta 3), namely fibrinogen, fibronectin and von Willebrand factor (vWF). The
      snake-venom proteins preferentially inhibited the adhesion of ADP-treated
      platelets to one or more of the immobilized ligands. Kistrin and dendroaspin
      exhibited similar inhibitory characteristics, abrogating platelet adhesion to
      fibrinogen and vWF at nanomolar concentrations, but poorly inhibiting adhesion to
      fibronectin. Kistrin and dendroaspin share little overall amino-acid-sequence
      identity, but a considerable level of sequence similarity exists around the RGD
      tripeptide. Synthetic cyclic peptides corresponding to these regions of kistrin
      and dendroaspin inhibited platelet adhesion to both fibrinogen and fibronectin
      with approximately equal potency, but were 100-fold weaker antagonists of the
      interactions of the alpha IIb beta 3 complex with fibrinogen than their parent
      proteins. The disintegrins elegantin and albolabrin, which share approx. 60%
      overall amino-acid-sequence similarity with kistrin but have different residues
      around the RGD tripeptide, exhibited different antagonistic preferences.
      Elegantin inhibited platelet adhesion to immobilized vWF and fibronectin, but was
      significantly less effective at disrupting adhesion to fibrinogen. Albolabrin
      selectively inhibited platelet adhesion to immobilized vWF and was less effective
      with fibrinogen and fibronectin as adhesive ligands. In contrast with the
      behaviour of these venom proteins, the adhesion of ADP-treated platelets to
      immobilized fibrinogen, fibronectin and vWF was inhibited non-selectively by a
      range of monoclonal antibodies with specificity for the alpha IIb beta 3 complex.
      These observations, therefore, define antagonistic preferences in this panel of
      venom proteins towards the interactions of the alpha IIb beta 3 complex with
      three immobilized glycoprotein ligands.

PMID- 7529493
TI  - The alpha-5 segment of Bacillus thuringiensis delta-endotoxin: in vitro activity,
      ion channel formation and molecular modelling.
AB  - A peptide with a sequence corresponding to the highly conserved alpha-5 segment
      of the Cry delta-endotoxin family (amino acids 193-215 of Bacillus thuringiensis
      CryIIIA [Gazit and Shai (1993) Biochemistry 32, 3429-3436]), was investigated
      with respect to its interaction with insect membranes, cytotoxicity in vitro
      towards Spodoptera frugiperda (Sf-9) cells, and its propensity to form ion
      channels in planar lipid membranes (PLMs). Selectively labelled analogues of
      alpha-5 at either the N-terminal amino acid or the epsilon-amine of its lysine,
      were used to monitor the interaction of the peptides with insect membranes. The
      fluorescent emission spectra of the 7-nitrobenz-2-oxa-1,3-diazole-4-yl (NBD)
      labelled alpha-5 peptides displayed a blue shift upon binding to insect
      (Spodoptera littoralis) mid-gut membranes, reflecting the relocation of the
      fluorescent probes to an environment of increased apolarity, i.e. within the
      lipidic constituent of the membrane. Moreover, midgut membrane-bound NBD-labelled
      alpha-5 peptides were protected from enzymic proteolysis. Functional
      characterization of alpha-5 has revealed that it is cytotoxic to Sf-9 insect
      cells, and that it forms ion channels in PLMs with conductances ranging from 30
      to 1000 pS. A proline-substituted analogue of alpha-5 is less cytolytic and
      slightly more exposed to enzymic digestion. Molecular modelling utilizing
      simulated annealing via molecular dynamics suggests that a transbilayer pore may
      be formed by alpha-5 monomers that assemble to form a left-handed coiled coil of
      approximately parallel helices. These findings further support a role for alpha-5
      in the toxic mechanism of delta-endotoxins, and assign alpha-5 as one of the
      transmembrane helices which form the toxic pore. The suggested role is consistent
      with the recent finding that cleavage of CryIVB delta-endotoxin in a loop between
      alpha-5 and alpha-6 is highly important for its larvicidal activity
      [Angsuthanasombat, Crickmore and Ellar (1993) FEMS Microbiol. Lett. 111, 255
      262].

PMID- 7529498
TI  - Increased tyrosine-phosphorylation of 55KDa proteins in beta-actin/Tec transgenic
      mice.
AB  - Protein-tyrosine kinases are considered to play important roles in cell
      proliferation and differentiation. Tec is a cytoplasmic protein-tyrosine kinase
      expressed in liver and hematopoietic tissues. To better understand Tec function
      in vivo, we generated transgenic mice expressing tec driven by the
      cytomegarovirus enhancer and beta-actin promoter. Among six transgenic lines
      generated, a particular line, named 2-11, expressed tec transgene product more
      widely and abundantly than the other lines. In the tissues of 2-11, the kinase
      activity of Tec was enhanced in accordance with the high expression of tec
      transgene product. Interestingly, tyrosine-phosphorylation of approximately 55KDa
      proteins in the tissues was induced. These results suggest that cellular proteins
      of 55KDa might be potential substrates of Tec in vivo.

PMID- 7529496
TI  - Nitric oxide activates metalloprotease enzymes in articular cartilage.
AB  - Nitric oxide (NO.) is a multifunctional messenger molecule generated by a family
      of enzymes, collectively termed the nitric oxide synthases. We investigated the
      role of NO. in the modulation of two metal-dependent proteolytic enzymes
      (collagenase and stromelysin) which are activated during inflammatory and
      infective arthritis. The inflammatory mediators interleukin-1 beta (IL-1 beta),
      tumor necrosis factor-alpha (TNF-alpha) and the bacterial cell wall fragment
      endotoxin, induced both nitric oxide synthase activity and stromelysin and
      collagenase activity in whole cell preparations and in conditioned media from
      explants of bovine and human cartilage. Both NO2- (the stable end-product of NO.)
      and metalloprotease activity were inhibited by competitive inhibitors of nitric
      oxide synthase. The NO. donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP) also
      induced metalloprotease activity in a dose-dependent fashion. These data provide
      evidence that NO. plays a regulatory role in the activation of metal-dependent
      proteases in articular chondrocytes and cartilage.

PMID- 7529499
TI  - Empigen BB: a useful detergent for solubilization and biochemical analysis of
      keratins.
AB  - Intermediate filament (IF) proteins make up some of the most insoluble proteins
      known, and within the IF protein family, keratins are the least soluble. We
      compared the efficiency of nonionic, cationic, mixed nonionic and anionic, and
      zwitterionic detergents in solubilizing keratins from insect cells that express
      recombinant human keratins and from human colonic cell lines and normal
      keratinocytes. The cationic detergent cetyltrimethylammonium bromide was similar
      to the zwitterionic detergent Empigen BB in its ability to efficiently solubilize
      keratins, but the latter detergent was superior in that it maintained antibody
      reactivity and allowed for immunoprecipitation of the keratins. Although Nonidet
      P40 partially solubilizes keratins, Empigen BB solubilizes a significant amount
      of keratins not solubilized by Nonidet-P40. In the case of vimentin, differences
      in solubilization efficiency among the detergents was not as dramatic as with
      keratins. Our results show that Empigen BB solubilizes a significant amount of
      epidermal and glandular keratins while preserving antigenicity. This detergent
      should prove useful for carrying out biochemical and molecular studies on these
      proteins and may be similarly beneficial for other IF proteins.

PMID- 7529497
TI  - Mutation of potential phosphorylation sites in the recombinant R domain of the
      cystic fibrosis transmembrane conductance regulator has significant effects on
      domain conformation.
AB  - Mutation of potential cAMP dependent protein kinase sites in the R domain of the
      cystic fibrosis transmembrane conductance regulator has significant effects on
      protein function. Mutation of the potential phosphorylation sites from serine to
      alanine, to abolish the site, reduced sensitivity to activation, or to glutamic
      acid, to mimic phosphorylation, caused some constitutive activity. To explore the
      structural effects of these mutations, recombinant R domain peptides were
      studied: the wild type, a mutant with nine serine residues changed to alanine,
      and a mutant with eight serine residues changed to glutamic acid. As assessed by
      C.D. spectroscopy, the mutants have substantially different secondary structure
      than the wild type, in agreement with the predictive algorithm of Gascuel and
      Golmard. The results show that mutagenesis of residues alters the polypeptide
      structurally as well as preventing it from serving as a phosphorylation
      substrate. Hence, the functional consequences of the mutations may not be
      entirely due to effects on phosphorylation.

PMID- 7529500
TI  - The protective effect of tetrahydrobiopterin on the nitric oxide-mediated
      inhibition of purified nitric oxide synthase.
AB  - The nitric oxide synthases (NOS) are a class of enzymes responsible for the
      generation of NO via an oxygen and NADPH dependent oxidation of the amino acid
      arginine. These enzymes are ironheme proteins which contain FAD and FMN and,
      enigmatically, require tetrahydrobiopterin (BH4). NOS has recently been shown to
      be subject to inhibition by its product, NO. Preliminary data by us indicate that
      a possible role for BH4 is to prevent and/or reverse the NO-mediated inhibition
      of NOS. The objective of this study was to elucidate the mechanism by which BH4
      protects NOS against NO inhibition. Protection of NOS from NO inhibition was
      observed by both BH4 and the BH4 regeneration system, dihydropteridine reductase
      (DHPR)/NADH. NO, rather than an oxidation product, appears to be the inhibitory
      species. Protection by BH4 is not likely due to a simple chemical reaction
      between BH4 and NO or its oxidation product, NO2. The results are consistent with
      a protective mechanism by which BH4 may act as a nonstoichiometric reducing agent
      for a redox active enzyme component, such as the ironheme, to prevent NO
      ligation.

PMID- 7529501
TI  - Rat Pit-1 stimulates transcription in vitro by influencing pre-initiation complex
      assembly.
AB  - The anterior pituitary-specific transcription factor, Pit-1, activates prolactin,
      growth hormone, TSH beta, growth hormone receptor genes and autoregulates the pit
      1 gene. Its mechanism of transcription activation is unknown. Using immobilized
      DNA templates and order-of-addition transcription assays, it is shown that Pit-1
      is required during pre-initiation complex assembly to activate the prolactin gene
      in vitro. Using prolactin promoters containing point mutations in the distal TATA
      box, it is also demonstrated that Pit-1 activation in vitro is not mediated
      simply by repressing the upstream, alternative promoter. Experiments show that a
      preformed class II pre-initiation complex is refractory to Pit-1 influence. The
      data indicate that Pit-1, and perhaps other members of the POU-protein family,
      activate transcription by influencing the type pre-initiation complex assembled
      on target promoters.

PMID- 7529502
TI  - Differential modulation by protein kinase C of progesterone-activated responses
      in human sperm.
AB  - Progesterone exerts important effects on human spermatozoa by rapid non genomic
      mechanisms of action. It has been demonstrated that processes triggered by this
      steroid are dependent on the activation of calcium influx through the plasma
      membrane. Beside calcium, progesterone also induces a rapid plasma membrane
      depolarization that is dependent on an influx of sodium through a putative
      progesterone-activated channel located on the plasma membrane. In this study we
      show that protein-kinase C inhibition inhibits calcium influx activated by
      progesterone, while leaving the depolarizing effect of this steroid unchanged.
      These results may be explained by the existence of two progesterone receptors on
      human sperm plasma membrane, one responsible for calcium influx and modulated by
      protein-kinase C and the other selectively permeable to sodium that is not under
      protein-kinase C control. Alternatively, protein-kinase C inhibition might change
      ion selectively of a single progesterone-activated channel, thus decreasing
      calcium permeability, while leaving sodium permeability unchanged.

PMID- 7529503
TI  - The role of nitric oxide in the central control of blood pressure.
AB  - In these studies blood pressure responses to intracerebroventricular (i.c.v.)
      infusions were recorded in anesthetized rats. NO donors caused a fall in blood
      pressure, whereas L-NAME, which blocks the enzyme (NOS) that produces NO, caused
      a rise in blood pressure. Calcium, i.c.v., stimulates NOS to lower blood
      pressure. The depressor action of NO is reduced by blocking the action of cGMP.
      This central NO/cGMP system is tonically active to maintain blood pressure at a
      normal level.

PMID- 7529504
TI  - Preclinical testing of iopromide. 1st communication: pharmacological evaluation.
AB  - Pharmacological and pharmacokinetic characteristics of the non-ionic monomeric X
      ray contrast agent iopromide (Ultravist, CAS 73334-07-3) were evaluated in
      preclinical studies. The scope of investigations included in vitro tests such as
      the determination of protein binding, the inhibition of complement, lysozyme,
      urokinase, platelet aggregation, the release of histamine, the influence on
      thromboplastin time. In vivo studies included bleeding time in rat, neural
      tolerance after intracisternal injection or administration into the carotid
      artery. Pharmacokinetic studies were performed in rats and dogs. Iopromide could
      be shown to be well tolerated in all the tests and species. Its pharmacokinetics
      was in agreement with the characteristics of an extracellular contrast agent with
      rapid renal elimination.

PMID- 7529506
TI  - Rapid fetal hemoglobin estimation assay during cordocentesis.
AB  - A method for rapid estimation of fetal blood content during cordocentesis is
      described. This procedure gives an opportunity to determine the contamination of
      the fetal sample by maternal blood as soon as possible. The method is based on
      the ability of fetal hemoglobin to resist denaturation in alkaline conditions,
      and can be used routinely. Fetal blood samples show a lower degradation rate
      (range 1.2-8.2%) compared to the maternal samples (range 25.0-52.5%). The method
      has the capacity to discriminate fetal and maternal samples with regard to their
      fetal hemoglobin content.

PMID- 7529505
TI  - Deletion analysis of protein kinase C inactivation by calphostin C.
AB  - Protein kinase C (PKC) undergoes specific inactivation by nanomolar
      concentrations of calphostin C. Both PKC-alpha (a Ca(2+)-dependent conventional
      isoform) and PKC-epsilon (a Ca(2+)-independent novel isoform) are similarly
      inactivated by calphostin C (75-100 nM produced 50% inhibition), suggesting that
      inactivation requires a site common to both classes of PKC. We therefore
      performed studies to identify a critical region in the regulatory domain of PKC
      alpha required for inactivation by calphostin C. A series of N-terminal
      truncation mutants of bovine PKC-alpha expressed in Saccharomyces cerevisiae was
      tested with 500 nM calphostin C, a concentration sufficient to inactivate wild
      type PKC-alpha by 80-90%. This concentration was as effective with mutant
      proteins containing deletions of up to 91 amino acid (aa) residues from the amino
      terminus (ND91), whereas a mutant protein truncated by 140 aa (ND140) was
      inactivated by only 20%. These findings imply that the aa sequence 92-140 is a
      structural determinant of PKC-alpha inactivation by calphostin C. This sequence
      contains one of the phorbol ester-binding sites (aa 102-144), which is highly
      conserved among most PKC isoforms including PKC-epsilon. In addition to aa 92
      140, PKC-stimulating cofactors (phosphatidylserine, phorbol ester, and Ca2+) are
      required for inactivation by calphostin C even in the case of PKC mutants that do
      not require these cofactors for enzymatic activity. These results suggest that
      cofactors provide a template that is required for productive interaction of PKC
      and the inhibitor. The significance of the proposed proximity effect to
      calphostin C action is discussed.

PMID- 7529507
TI  - Evaluation of proviral copy number and plasma RNA level as early indicators of
      progression in HIV-1 infection: correlation with virological and immunological
      markers of disease.
AB  - OBJECTIVE: We compared the proviral DNA level in peripheral blood mononuclear
      cells (PBMC), viral RNA level in plasma, presence of p24 antigen in serum, viral
      phenotype, and results of immunological markers of HIV-1 disease. METHODS:
      Consecutive samples of 62 HIV-1-infected patients, representing all stages of
      disease were tested for proviral DNA in PBMC and viral RNA in plasma using a semi
      quantitative limiting dilution polymerase chain reaction (PCR). The presence of a
      syncytium-inducing (SI) phenotype was assessed after direct cocultivation of
      patient PBMC with MT-2 cells. Results of the quantitative PCR and the MT-2
      coculture were correlated with the clinical stage of the disease, with the number
      of CD4+ T cells, and with the results of other virological and immunological
      markers, such as the level of p24 antigen, beta 2-microglobulin (beta 2M) and
      neopterin. RESULTS: Significant differences were observed between the results for
      asymptomatic and symptomatic patients for all markers under study. In the group
      of asymptomatic patients with a CD4+ T-cell count > 200 x 10(6)/l, patients with
      high amounts of proviral DNA had significantly higher amounts of beta 2M,
      neopterin and viral RNA, they were more frequently p24 antigen-positive and
      harboured more frequently SI strains than patients with low amounts of proviral
      DNA. A good correlation between the proviral DNA and the viral RNA levels was
      observed. Significant changes of viral RNA but not proviral DNA levels were
      observed after initiation of therapy or when therapy failed. CONCLUSIONS: We
      demonstrated the relationship between high proviral DNA level in PBMC, high viral
      load in plasma, elevated beta 2M and neopterin concentrations in serum, and the
      presence of p24 antigen in serum in a group of asymptomatic patients with a CD4+
      T-cell count > 200 x 10(6)/l. We suggest the possible usefulness of proviral load
      as an early indicator of disease progression. The presence of SI strains is
      highly correlated with disease; however, SI strains were detected in only 46% of
      symptomatic patients. It also appeared that the measurement of viral RNA levels
      is a useful marker for therapy monitoring.

PMID- 7529510
TI  - The effect of a hyposmotic shock on amino acid efflux from lactating rat mammary
      tissue: stimulation of taurine and glycine efflux via a pathway distinct from
      anion exchange and volume-activated anion channels.
AB  - We have examined the effect of a hyposmotic shock, and thus cell swelling, upon
      the efflux of amino acids, SO4(2-) and I- from lactating mammary tissue. A
      hyposmotic challenge increased the efflux of taurine and glycine via a 4,4'
      diisothiocyanatostilbene-2,2'- disulphonic acid (DIDS)-sensitive pathway. It
      appears that these amino acids do not exit via an anion-exchange mechanism
      following cell swelling because sulphate efflux, which uses a DIDS-sensitive
      exchange mechanism, was unaffected. The hyposmotic-induced efflux of taurine was
      not dependent upon the Na+ gradient and was not influenced by the nature of the
      anion in the incubation medium. In addition, taurine efflux was stimulated by
      incubating mammary tissue in an isosmotic medium that contained urea, suggesting
      that cell swelling is the stimulating factor rather than a decrease in osmolality
      per se. The results suggest that mammary tissue uses taurine and glycine as a
      means of regulating cell volume following swelling. In contrast, the efflux of
      glutamic acid, alanine and alpha-aminoisobutyric acid was unaffected by a
      hyposmotic challenge. Similarly, the efflux of I- was unaffected by such a
      challenge. The results suggest that volume-activated amino acid transport in
      lactating rat mammary tissue is distinct from volume-regulated anion channels.

PMID- 7529509
TI  - Laminin mediates the restitution of rat gastric mucosa in vitro.
AB  - Restitution, the rapid re-establishment of mucosal integrity following damage,
      involves cell migration and can be monitored by measuring transmucosal potential
      difference of tissue mounted in an Ussing chamber. The involvement of
      extracellular matrix proteins and matrix receptors was examined in the
      restitution of rat gastric mucosa. Undamaged mucosa maintained a potential
      difference of -32.7 +/- 2.2 mV for several hours. Mucosal exposure to 0.6 M NaCl
      for 1 min reduced this to -3.3 +/- 1.4 mV in 2-3 min. Thereafter, the potential
      difference returned in 60 min to plateau at -28.9 +/- 1.3 mV (88.5 +/- 3.6% of
      pre-exposure). Tissues mucosally treated with 1:100 anti-laminin antiserum
      maximally recovered following damage to 65.6 +/- 6.6% of pre-exposure potential
      difference (PD), while those treated with 1:100 anti-collagen IV or anti
      fibronectin antisera recovered to 88.8 +/- 9.7% and 86.3 +/- 3.2%, respectively.
      Only the anti-laminin result was significantly different from controls. The anti
      laminin effect was abolished by pre-incubation of the anti-laminin antiserum with
      purified rat laminin, suggesting that the effect was laminin specific. In
      experiments involving matrix protein receptors, tissues treated with alpha
      lactalbumin, a protein altering the substrate specificity of cell surface laminin
      receptor/enzyme beta-1,4-galactosyltransferase, maximally recovered following
      damage to only 49.3 +/- 7.7% of pre-exposure PD, which was significantly
      different from controls, while those treated with anti-beta 1 integrin recovered
      to 85.0 +/- 9.7%. Our data suggest that laminin is involved in mediation of
      gastric mucosal restitution, possibly via beta-1,4-galactosyltransferase.

PMID- 7529511
TI  - Interaction between secretin and nerve-mediated amylase secretion in the isolated
      exocrine rat pancreas.
AB  - This study investigates the effects of the gut peptide, secretin, on nerve
      mediated and acetylcholine-evoked amylase secretion and calcium (Ca2+) and
      magnesium (Mg2+) mobilization in the in vitro rat pancreas. Both electrical field
      stimulation (EFS; 50 V, 20 Hz, 1 ms) and acetylcholine (ACh; 10(-6) M) caused
      marked increases in amylase output in isolated pancreatic segments. These
      responses were inhibited by atropine (10(-5) M). Secretin (10(-10) and 10(-8) M)
      evoked only a small increase in amylase secretion, which was unaffected by
      atropine. Combining either EFS or ACh with secretin resulted in an attenuation in
      amylase output compared with the response obtained with either EFS or ACh alone.
      In a Mg(2+)-free medium, secretin failed to inhibit the amylase output evoked by
      EFS. When forskolin (10(-5) M) was combined with EFS there was a marked
      potentiation of amylase output. In fura-2-loaded acinar cells, ACh (10(-6) M)
      elevated cytosolic free Ca2+ concentration ([Ca2+]i). Secretin alone had no
      detectable effect on [Ca2+]i compared with basal values, but it attenuated the
      ACh-induced elevation of [Ca2+]i. Both EFS and ACh elicited 45Ca2+ influx,
      whereas secretin had no significant effect. In the presence of secretin the EFS-
      and ACh-induced 45Ca2+ influx was reduced compared with responses obtained with
      either EFS or ACh alone. EFS caused a net efflux of Mg2+, whereas secretin alone
      evoked a net uptake of Mg2+ in pancreatic segments. Combining secretin with EFS
      resulted in a net uptake of Mg2+. In mag-fura-2-loaded acini ACh (10(-5) M)
      stimulated an initial transient rise in cytosolic free Mg2+ concentration
      ([Mg2+]i) followed by a sustained decrease in [Mg2+]i. Stimulation of acinar
      cells with secretin (10(-8) M) resulted in an elevation in [Mg2+]i compared with
      the resting level. When ACh (10(-5) M) was combined with secretin there was an
      initial increase in [Mg2+]i followed by a marked decrease to the pre-secretin
      stimulated value. The results indicate that secretin may control nerve-mediated
      and ACh-evoked secretory responses in the rat pancreas, possibly by an
      interaction between cellular Ca2+ and Mg2+.

PMID- 7529508
TI  - Lack of excision of introns from primary transcripts of certain chicken
      vitellogenin II minigenes.
AB  - Two truncated versions of the chicken vitellogenin II gene VTGII were designed
      and constructed to include all known essential regulatory elements of the
      complete gene. Both pCB123 and pCB123/4 contain 945 base pairs (bp) of the 5'
      flanking sequence, introns and exons 1-3, and a subset of the remaining 32 exons
      of VTGII, inserted into a pBluescript SK (+/-) vector. pCB123/4 contains 752 bp
      of legitimate VTGII 3'-flanking sequences, while the 3' end of pCB123 terminates
      at the VTGII cDNA end, followed by AT-tailing and vector sequences carried over
      during cloning. Expression of these plasmids was tested following their
      lipofection into primary cultures of chicken hepatocytes established from day 14
      embryos. Poly(A)+ RNA derived from pCB123 was detected by Northern blotting and
      reverse transcription-polyacrylamide chain reaction. No evidence was observed for
      appropriate hormonal control of expression, despite the presence of 17 beta
      estradiol or colipofection with the estrogen receptor clone pHEO. VTGII sequences
      at the 3' end of pCB123/4 led to an apparent destabilization of the RNA
      transcript. Unexpectedly, unprocessed pCB123 transcripts of varying lengths
      accumulated in the cells. These experiments constitute the first reported
      attempts to express authentic VTGII coding sequences in cultured cells and
      highlight the dilemma of which introns to include in a minigene. Despite reports
      that some minigenes are expressed more efficiently if one or two introns are
      included, other minigenes may be expressed more effectively in the absence of
      introns. In the case of a complex gene with many introns, such as VTGII, there
      may be a preferential order in which introns are removed from the primary
      construct. The truncation of complex genes to give functional minigenes for
      transgenic studies may require considerable experimentation.

PMID- 7529512
TI  - Quick methylene blue staining for visualizing virus plaques in titration
      experiments.

PMID- 7529513
TI  - Generating customized, long-lived 32P-labeled RNA size markers.

PMID- 7529514
TI  - UV cross-linking of RNA to nylon membrane is suitable for northern blot
      hybridization using a digoxigenin-labeled DNA probe.

PMID- 7529517
TI  - Enhancement of lymphokine-activated killer cell cytotoxicity implicated by
      surface adhesion molecule expression on tumor cell lines pretreated with anti
      cancer agents.

PMID- 7529515
TI  - Strategy for epitope tagging the protein-coding region of any gene.
AB  - We describe the construction of a plasmid carrying a DNA cassette encoding the
      influenza virus hemagglutinin (HA1) epitope. Insertion of this cassette into the
      coding region creates a gene encoding an epitope-tagged protein. The tagged
      protein can be detected and quantified by using a commercially available anti-HA1
      antibody. A one-step procedure introduces the epitope at any restriction site
      within a gene while maintaining the open reading frame. An example of the
      application of this technique is presented and the different uses of the cassette
      are discussed.

PMID- 7529516
TI  - A phase I-II study of cyclophosphamide, epidoxorubicin, levofolinic acid/5
      fluorouracil and recombinant human granulocyte colony stimulating factor in
      metastatic breast carcinoma.
AB  - Thirty patients with measurable metastatic breast carcinoma were treated with a
      combination of cyclophosphamide 600 mg/m2 on day 1, levofolinic acid 100 mg/m2
      plus 5-fluorouracil 375 mg/m2 on days 1-3, and epidoxorubicin (EDXR) in three
      refracted doses on days 1-3 with G-CSF rescue for 10 days. In the phase I part of
      the study, groups of 3 patients received EDXR 20, 25, 30, 35, and 40 mg/m2/day
      until the dose limiting toxicity (DLT) was reached. At the dose of 40 mg/m2/day
      prolonged grade 4 leukopenia, severe proctitis, and grade 3 diarrhea represented
      the DLT. All subsequent patients were treated at the maximal tolerated dose of
      EDXR (35 mg/m2/day). In the group of 18 patients treated at 35 mg/m2/day the
      overall response rate was 78%, with 22% CR and 56% PR. Four patients did not
      respond. Objective responses were seen at all tumor sites including bone and
      viscera, which usually are rather chemotherapy insensitive. Toxicity was
      generally acceptable. Although the response rate was quite high, the duration of
      objective tumor regression and patients' survival were not impressive. In
      conclusion, we do not recommend routine use of such an aggressive regimen for
      palliation of advanced breast cancer. Results of the present and similar studies
      may, however, be useful for planning of neoadjuvant or adjuvant trials with
      curative intent.

PMID- 7529518
TI  - Phylogenetic aspects of the occurrence and distribution of secretogranin II
      immunoreactivity in lower vertebrate gut.
AB  - A novel monoclonal antibody raised against bovine secretogranin II (Sg II) was
      used in immunohistochemical studies on amphibian (Rana esculenta), reptilian
      (Podarcis sicula) and avian (Gallus gallus) gut. Sg II immunoreactivity was
      detected in epithelial and nervous elements. Cells immunoreactive for Sg II were
      examined by double immunostainings to determine whether they might also co-store
      certain previously known bioactive amine/peptide substances. Almost all the
      endocrine cells immunoreactive for bombesin, substance P, neurotensin,
      gastrin/cholecystokinin, neuropeptide tyrosine (NPY) and calcitonin gene-related
      peptide as well as some of those immunostained for serotonin, histamine, and
      polypeptide tyrosine tyrosine (PYY) also contained Sg II. Sg II-immunoreactive
      cells varied in number and distribution according to regions of the gut and
      animal species. The number of Sg II immunoreactive granules notably varied not
      only according to cell type, but also within the same cell population. Many
      histamine-, calcitonin gene-related peptide (CGRP)-, substance P-, PYY-, and
      neurotensin-immunoreactive neurons also contained Sg II. These were mostly
      situated in the myenteric plexus; their distribution pattern varied among the
      three species. These findings show that, despite being well conserved during
      phylogeny, Sg II has a heterogeneous distribution.

PMID- 7529519
TI  - NADPH-diaphorase is colocalized with nitric oxide synthase and vasoactive
      intestinal polypeptide in rat pancreatic neurons in culture.
AB  - NADPH-diaphorase activity together with nitric oxide synthase- and vasoactive
      intestinal polypeptide-immunoreactivities were examined in the neurons of the rat
      pancreas in culture. Nitric oxide synthase (NOS)- and vasoactive intestinal
      polypeptide (VIP)-immunoreactivities were localized in a subpopulation of neurons
      which were also NADPH-diaphorase positive. All neurons expressing colocalized
      activities for NOS/VIP and NADPH-diaphorase were solitary cells in culture. Each
      of these double-labelled neurons was characterized by a round or oval cell body,
      with short and long processes emanating from it. Some of these processes
      traversed several micrometres before terminating on the exocrine acinar and
      endocrine cells. The present study provides evidence that nitric oxide may act as
      a regulatory agent in the inhibitory neural control of the secretory functions in
      the pancreas, thereby maintaining the milieu interieur of the organism.

PMID- 7529520
TI  - Reheparinisation requirements after cardiopulmonary bypass in patients treated
      with aprotinin.
AB  - OBJECTIVE: To determine reheparinisation requirements following protamine
      neutralisation after the discontinuation of cardiopulmonary bypass in a group of
      patients receiving "low dose" aprotinin compared with a control group. DESIGN:
      Randomised, placebo controlled study. SETTING: Regional cardiothoracic unit
      within a district general hospital. PATIENTS: 20 patients were consecutively
      allocated to one of two groups. All patients had a primary elective aortocoronary
      bypass operation using standard anaesthetic techniques and no patient was
      withdrawn from the study. INTERVENTIONS: Aprotinin group patients (n = 9)
      received aprotinin (1 x 10(6) kallikrein inactivator units (KIU)) as an
      intravenous bolus after the induction of anaesthesia, and 1 x 10(6) KIU was added
      to the pump prime. Control group patients (n = 11) received 0.9% saline placebo.
      MAIN OUTCOME MEASURES: Activated clotting time (ACT), heparin concentration, and
      heparin dose response (HDR) measured before, during, and after bypass. The HDR is
      an accurate method to determine the patients' in vitro response to heparin and is
      used to predict the dose of heparin required to attain an ACT of 400 seconds.
      RESULTS: Activated clotting times were similar in the two groups for the duration
      of the study. Heparin concentrations were zero in all patients before heparin
      administration and after protamine neutralisation. During bypass there was no
      difference between the groups. The median heparin dose response was the same in
      the two groups before the administration of heparin, but after the neutralisation
      of heparin with protamine after the discontinuation of bypass the HDR was
      significantly higher in the aprotinin group for up to one hour (median of 2.9
      IU/ml v 1.25 in the control group at 10 minutes after protamine neutralisation, P
      < 0.01; 2.5 v 1.45 at 30 minutes, P < 0.05; and 2.9 v 1.6 at one hour, P <
      0.001). CONCLUSION: Heparin requirements were nearly doubled in patients treated
      with aprotinin, who required reheparinisation for up to one hour after protamine.
      This relative "heparin resistance" cannot be explained by the presence of
      excessive protamine. Aprotinin may be a substrate for the N-carboxypeptidase that
      destroys protamine, thus indirectly enhancing and prolonging the activity of
      protamine.

PMID- 7529522
TI  - Mitomycin-ifosfamide-cisplatinum (MIP) vs MIP-interferon vs cisplatinum
      carboplatin in metastatic non-small-cell lung cancer: a FONICAP randomised phase
      II study. Italian Lung Cancer Task Force.
AB  - The FONICAP group is screening, with randomised phase II studies, the activity of
      new chemotherapy programmes for advanced non-small-cell lung cancer (NSCLC)
      looking for regimens with > 30% activity. In the present study, three regimens
      were tested: MIP (mitomycin 6 mg m-2, ifosfamide 3 g m-2, cisplatinum 80 mg m-2
      on day 1 every 28 days); MIP-IFN (MIP and interferon alpha-2b 3 MU s.c. three
      times a week); and PC (cisplatinum 60 mg m-2 and carboplatin 400 mg m-2 on day 1
      every 28 days). Overall 93 chemotherapy-naive patients were enrolled: 23 received
      MIP, 27 received MIP-IFN and 43 received PC. Eighty per cent of the patients had
      stage IV and 20% stage IIIb disease (positive pleural effusion or supraclavicular
      nodes). Response rates were as follows: MIP = 9% (95% CI 1-28%), MIP-IFN = 7%
      (95% CI 1-24%) and PC = 14% (95% CI 5-28%). The overall median survival was 183
      days. Grade III-IV leucopenia was observed in 36% of patients treated with MIP
      IFN vs 10% in the other two arms, and thrombocytopenia grade III-IV was reported
      in nearly 10% of patients overall. In conclusion, (1) all three regimens
      investigated have poor activity (< 30%); (2) when tested in multicentre
      randomised phase II trials, MIP displays lower activity than in phase II trials;
      (3) PC has similar activity to other platinum-containing regimens; (4) randomised
      phase II studies are a reliable and quick method of determining the anti-tumour
      activity of novel chemotherapeutic regimens in NSCLC.

PMID- 7529521
TI  - The effect of isolated chloride depletion on growth and protein turnover in young
      rats.
AB  - The effects of feeding a chloride-deficient (CD) diet were examined in young,
      growing rats. All animals were fed the same sodium-replete, CD diet. The
      experimental group drank distilled water, while the control group (CS) drank
      distilled water supplemented with 37 mM sodium chloride. By day 15, the CD rats
      had negligible concentrations of chloride in their urine and had developed
      hypochloremic metabolic alkalosis. Both groups had comparable urinary sodium
      concentrations and creatinine clearances. Food intake (256 vs. 226 g), weight
      (108.8 vs. 47.0 g) and length (9.6 vs. 7.4 cm) gains were greater in the CS
      animals and the efficiency of weight gain was lower in the CD rats (25.2 vs. 42.6
      g gained/g of food intake). After 15-18 days, blood was drawn for testing, body
      composition measurements were performed and epitrochlearis muscle protein
      synthesis and net degradation rates determined. When incubated with or without
      the addition of insulin (I), epitrochlearis muscle protein synthesis, measured as
      the incorporation of 14C-phenylalanine, was significantly lower in CD rats [(I+
      45.7 vs. 36.76) and (I-34.72 vs. 26.3) nmol phenylalanine/g wet weight per hour
      (both P < 0.05)]. Net protein degradation rates were not significantly different
      between the two groups. Estimated nitrogen balance was significantly diminished
      in CD compared with CS rats. Gastrocnemius muscle RNA concentrations were also
      lower in CD rats (1.34 vs. 1.60 mg RNA/g wet weight, P < 0.001), but
      gastrocnemius protein concentrations were equal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529523
TI  - Decrease in pulmonary function during bleomycin-containing combination
      chemotherapy for testicular cancer: not only a bleomycin effect.
AB  - This study was performed to determine the changes in pulmonary function in
      patients randomised to receive treatment with four cycles of bleomycin, etoposide
      and cisplatin (BEP) (27 patients) or with four cycles of etoposide and cisplatin
      (EP) (27 patients) for disseminated non-seminomatous testicular cancer. This
      enabled us to establish whether effects other than those due to bleomycin
      determined the detrimental effects of BEP on lung function assessments. Slow
      inspiratory vital capacity (VC), the transfer factor of the lungs for carbon
      monoxide (TLCO), the diffusing capacity of the alveolo-capillary membrane (Dm),
      the pulmonary capillary blood volume (Vc) and the transfer factor of the lungs
      for carbon monoxide per unit alveolar volume (KCO) were determined before and at
      3 week intervals during chemotherapy. Both groups, similar in terms of factors
      that may influence pulmonary function, showed during therapy a significant
      decrease in TLCO compared with the pretreatment value. Only at the end of the
      therapy was a significant difference in TLCO between both groups observed. Dm
      diminished also significantly in both groups during treatment, but differences
      between both groups were not seen. VC and Vc decreased in patients receiving BEP
      but remained constant during treatment with EP. It can be concluded that the Dm,
      KCO, and the widely used TLCO are not suitable parameters to monitor specifically
      pulmonary toxicity induced by bleomycin as part of a multidrug regimen. However,
      VC and Vc appear to be proper lung function assessments which reflect
      specifically alterations induced by bleomycin.

PMID- 7529525
TI  - Measurement of cytokeratin 19 fragments as a marker of lung cancer by CYFRA 21-1
      enzyme immunoassay.
AB  - Soluble cytokeratin fragment 19 levels were measured with an enzyme immunoassay
      method developed by Boehringer Mannheim (Enzymun-Test CYFRA 21-1) in the serum of
      185 patients with lung cancer [149 with non-small-cell lung cancer (NSCLC) and 36
      with small-cell lung cancer (SCLC)] and 97 patients with benign lung diseases in
      order to determine its clinical usefulness in the diagnosis of lung cancer and
      follow-up of treatment. We used the cut-off value of 3.5 ng ml-1, established by
      the Japan CYFRA research group. This cut-off value is based on calculations using
      the receiver operating characteristic approach instead of using the 95%
      specificity approach recommended by other authors. The resulting sensitivity and
      specificity for the group of all lung cancer patients were 65.4% and 84.5%
      respectively. The sensitivity was highest (76.1%) for squamous cell carcinoma and
      lowest (44.4%) for SCLC. For NSCLC patients, when CYFRA 21-1 levels were analysed
      by node (N) factor, patients who presented with mediastinal lymph node metastasis
      (N2 or N3) demonstrated higher serum CYFRA 21-1 levels (5.6; interquartile range
      3.2-11.5 ng ml-1) than patients without mediastinal node metastasis (N0 or N1,
      3.9; interquartile range 2.2-10.0 ng ml-1; Mann-Whitney U-test, P = 0.0373). We
      compared the discriminatory power of CYFRA 21-1 with that of other tumour markers
      including carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC)
      and neuron-specific enolase (NSE). The area under the curve (AUC) of each ROC
      curve was calculated using the CLABROC program for statistical analysis. CYFRA 21
      1 appeared to have the most discriminatory power of the markers tested in the
      diagnosis of lung cancer. In serial measurements of 14 patients receiving
      chemotherapy or radiotherapy, a high degree of correlation was noted between
      serum levels of CYFRA 21-1 and extent of clinical response (Wilcoxon, P =
      0.0093).

PMID- 7529527
TI  - Tissue polypeptide-specific antigen (TPS) in monitoring palliative treatment
      response of patients with gastrointestinal tumours.
AB  - The new proliferation marker, tissue polypeptide-specific antigen (TPS),
      representing the specific epitope M3 of tissue polypeptide antigen, and three
      conventional biochemical markers, CEA, CA 19-9 and CA-195, were analysed in 69
      patients with advanced gastrointestinal tumours. The aim of our study was to
      assess the clinical relevance of these markers and to determine whether their use
      in monitoring the course of the disease can reduce the need for serial imaging
      procedures. At baseline, pathologically elevated TPS levels occurred in 90% of
      patients. CEA was elevated in 73%, CA 19-9 in 59% and CA-195 in 68%. With a
      detection rate of > 90% in both advanced colorectal (n = 37) and pancreatic
      cancer (n = 20), and of 75% in gastric cancer (n = 12), TPS was the most
      sensitive marker in all three tumour types included in this analysis. Serial
      evaluations of TPS and other biochemical markers were available in 39 patients
      undergoing palliative systemic chemotherapy. Treatment with a fluorouracil-based
      regimen resulted in a partial response in 5/27 patients with colorectal cancer,
      whereas 2/12 patients with pancreatic cancer responded to therapy with a high
      dose epirubicin combination regimen. All other patients had disease stabilisation
      or suffered from progressive disease. When compared with the results of serial CT
      scanning, the TPS correlated best with the course of the disease, the positive
      predictive value being 75% for a partial response, 96% for stable disease and
      partial response combined and 100% for progressive disease. The corresponding
      values for CEA were 50%, 81% and 62% and were similar to those for CA 19-9 and CA
      195. In summary, TPS seems to represent a sensitive, clinically relevant and
      specific marker of proliferative activity in gastrointestinal cancer. According
      to our preliminary results in colorectal and pancreatic cancer, TPS may be
      considered as the primary means of monitoring treatment, and imaging reduced to
      confirm the response.

PMID- 7529526
TI  - Galactosylated streptavidin for improved clearance of biotinylated intact and
      F(ab')2 fragments of an anti-tumour antibody.
AB  - Persistence of high levels of radiolabelled antibody in the circulation is a
      major limitation of radioimmunotherapy. Biotinylation of the radiolabelled anti
      tumour antibody followed by administration of streptavidin is known to give much
      improved tumour to blood ratios as the radioantibody is complexed and
      subsequently cleared via the reticuloendothelial system, although prolonged
      splenic uptake is a problem. We have investigated the effect on the clearance
      pattern and tumour localisation of a 125I-labelled biotinylated anti-CEA antibody
      (A5B7) after administration of a galactosylated form of streptavidin (gal
      streptavidin) in nude mice bearing a human colon carcinoma xenograft. Fifteen
      minutes to 1 h after gal-streptavidin administration the complexes were cleared
      via the liver alone (as opposed to liver and spleen after native streptavidin).
      Twenty-four hours after administration of gal-streptavidin, the tumour to blood
      ratio for biotinylated A5B7 IgG increased from 2.9 to 13.2 and for biotinylated
      F(ab')2 fragments an increase from 4.9 to 33.2 was achieved. The reduction in
      tumour accumulation of F(ab')2 24 h after injection of the clearing agent was
      less than that seen with intact antibody. Injection of asialofetuin inhibited
      clearance, confirming that removal of the gal-streptavidin-biotinylated antibody
      complexes from the blood was via the asialoglycoprotein receptor on liver
      hepatocytes. Therefore, galactosylation of the streptavidin clearing agent allows
      rapid removal of radiolabelled biotinylated antibodies via the liver
      asialoglycoprotein receptor, as opposed to the reticuloendothelial system.

PMID- 7529524
TI  - Heterogeneity in the in vitro survival and proliferation of human seminoma cells.
AB  - The in vitro culture conditions allowing survival and initial proliferation of
      murine primordial germ cells from 10.5 days post coitum embryos, which include
      the use of a murine embryonal fibroblast (STO) feeder, were applied to 21 human
      seminomas, composed of tumour cells which are considered as the malignant
      counterparts of human primordial germ cells. Cells from 18 seminomas attached
      poorly to STO, and only a few survived through day 10. In contrast, three
      seminomas showed a higher degree of attachment. Two of them showed initial
      proliferation and enhanced survival: 30 days for tumour SE1 and 25 days for
      tumour SE3. Tumour SE1 was more extensively studied, using the culture conditions
      allowing the derivation of pluripotent embryonic stem cells from 8.5 days post
      coitum murine primordial germ cells, which include the use of STO feeder, stem
      cell factor, leukaemia inhibitory factor and basic fibroblast growth factor. The
      presence of stem cell factor was necessary and sufficient for colonies of tumour
      cells to form during the first 3 days of culture. While the cell number decreased
      after day 3 in medium without fetal calf serum, it increased until day 9 in
      medium containing fetal calf serum. No reprogramming of SE1 cells to pluripotent
      stem cells was observed. Our data indicate that seminomas form a tumour
      population with a heterogeneous in vitro behaviour not equivalent to that of 8.5
      10.5 days post coitum murine primordial germ cells.

PMID- 7529528
TI  - Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis
      studied by localized magnetic resonance proton spectroscopy.
AB  - Previously we have shown that short-term myeloid growth factor priming of
      haemopoiesis prior to bone marrow harvest increased the yield of myeloid
      progenitors in the graft. The present study is intended to investigate the
      expansion of haemopoiesis by volume selective proton magnetic resonance
      spectroscopy (MRS). Six patients were treated with daily subcutaneous injections
      of recombinant human granulocyte colony-stimulating factor (rhG-CSF, n = 2) or
      granulocyte-macrophage colony-stimulating factor (rhGM-CSF, n = 4) for 5d before
      marrow harvest. MRS investigations were performed prior to treatment (day 0), day
      5 and day 12. Spectroscopic examinations were performed with the stimulated echo
      acquisition mode (STEAM) method on a 1.5 T clinical whole-body imaging unit. A
      cubic volume of interest (VOI) was selected in the bone marrow of the left iliac
      bone. The patients responded with a rise in blood absolute neutrophil count from
      median 3.3 x 10(9)/l (range 1.3-7.3 x 10(9)/l) before to 15.6 x 10(9)/l (range
      6.8-22.0 x 10(9)/l) after treatment. Concomitantly an increase in bone marrow
      cellularity and myeloid:erythroid ratios documented the stimulation of
      myelopoiesis. During priming, the light-density cell proliferation rate in marrow
      samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9
      94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day
      7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3)
      (range 4.0-87.5/2.2-103.0) to 64/76 x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS
      detected a significant increase in bone marrow 'relative water content' day 12, 1
      week after myeloid growth factor treatment was stopped, from median 30.5% (range
      16-45) to 79% (range 56-93). In parallel, haemopoiesis was detected in new areas
      of femur. In conclusion, the non-invasive MRS method may be a useful and reliable
      in vivo examination for expansion of haemopoiesis and a correspondent reduction
      of fat tissue in bone marrow after priming with recombinant human haemopoietic
      growth factors.

PMID- 7529529
TI  - Haemopoietic colony-forming cells from peripheral blood stem cell harvests:
      cytokine requirements and lineage potential.
AB  - We have measured the in vitro growth requirements of progenitor cells released
      into the blood of cancer patients following administration of chemotherapy and
      cytokines. In order to distinguish the direct effects of cytokines on progenitors
      from those activating accessory cells, we have compared clonogenic growth before
      and after CD34-positive selection of progenitors, in serum-free conditions. CD34
      selection had little effect on the cytokine requirements of erythroid colony
      forming cells and single cytokines, particularly interleukin-3, could support
      considerable colony growth in both mononuclear and CD34+ cell suspensions.
      Optimal erythroid colony growth, however, usually required the addition of a
      combination of stem cell factor and interleukin-3, in addition to erythropoietin,
      which was always required. Maximal numbers of granulocyte-monocyte progenitors in
      mononuclear cell cultures, could be achieved with a mixture of stem cell factor,
      interleukin-3 and granulocyte-monocyte colony stimulating factor. However, after
      CD34 selection, full myeloid colony growth was only achieved when granulocyte
      colony stimulating factor was added to the above mixture. This presumably
      reflects loss of accessory cells, during CD34 selection, which produce this
      cytokine. When transplanted after 8 d of culture, 16/22 myeloid colonies from
      erythropoietin-free cultures of peripheral blood stem cell harvests, could
      generate secondary erythroid colonies implying that these progenitors are
      multipotential. However, surface marker analysis of individual erythroid colonies
      revealed only the occasional presence of granulocytes and monocytes. These data
      demonstrate that cytokine mixtures are required for optimal colony growth,
      particularly after CD34 selection, and that most mobilized, blood clonogenic
      cells are multipotential.

PMID- 7529532
TI  - Interleukin-3 administration enhances human monocyte function in vivo.
AB  - In addition to its haemopoietic effects, interleukin-3 (IL-3) enhances leucocyte
      function in vitro. In this study we examined the effects on haematological
      variables and monocyte function of a single IL-3 infusion in five
      haematologically normal individuals. There was a rapid fall in circulating
      monocyte (to 24 +/- 6% of pre-infusion value) and eosinophil numbers (to 3 +/-
      2%) with a nadir at 30 min and gradual return to baseline over 6 h. No
      significant changes in monocyte expression of the adhesion molecules CD11b or L
      selectin or of monocyte respiratory burst activity were detected. There was a
      significant increase in monocyte phagocytosis and killing of Candida after IL-3
      infusion: the percentage of monocytes which had ingested Candida increased from
      39 +/- 10% to 62 +/- 12% and the total number of Candida killed per 100 monocytes
      increased from 63 +/- 34 to 210 +/- 59 (P < 0.05 and P < 0.01 respectively).
      There was no inhibition of neutrophil migration into a 'skin window' site and
      monocyte migration was moderately enhanced (peak increase of 260 +/- 47%). These
      results show that IL-3 has significant effects on monocyte function in vivo and
      could be of use in augmenting host defence mechanisms in immunocompromised
      patients.

PMID- 7529533
TI  - Isobutyramide, an orally bioavailable butyrate analogue, stimulates fetal globin
      gene expression in vitro and in vivo.
AB  - Butyrate and other short-chain fatty acids stimulate fetal globin gene expression
      and have potential for ameliorating the beta globin disorders. Butyrate, however,
      is rapidly metabolized in vivo and reaches only micromolar concentrations in
      plasma. We report here that a branched-chain derivative of butyrate,
      isobutyramide, increases gamma globin gene expression in cultured human erythroid
      progenitors in vitro and stimulates activity from a minimal gamma globin gene
      promoter linked to a reporter gene in stable and transient expression assays,
      with slightly less activity in these in vitro assays than butyrate. In vivo,
      administration of isobutyramide to anaemic adult baboons rapidly stimulates fetal
      globin synthesis and F-reticulocyte production. Plasma concentrations at
      millimolar levels are achieved after a single intravenous or oral dose (500-600
      mg/kg), and these concentrations are maintained for 9.5-10.5 h. These results
      indicate that although isobutyramide has slightly less activity than butyrate in
      vitro in enhancing fetal globin expression at the cellular and molecular level,
      its prolonged in vivo half-life may provide superior activity as a therapeutic
      agent for reactivating fetal globin gene expression in vivo.

PMID- 7529531
TI  - Changes in light-scatter profile, membrane depolarization and calcium
      mobilization of neutrophils induced by G-CSF in vivo.
AB  - To extend our studies about phenotypical and functional alterations of G-CSF
      induced neutrophils we have evaluated their light-scatter profile, mobilization
      of intracellular calcium ([Ca2+]i) and membrane depolarization after stimulation.
      A significant increase in the forward scatter signals could be demonstrated in
      such neutrophils from patients with neutropenias of various origin and from
      healthy test subjects. This increase began 4 h and returned to normal 96 h after
      G-CSF injection in the latter group. We found an impairment of [Ca2+]i
      mobilization in neutrophils from patients with glycogen storage disease type IB
      after stimulation of these cells with fMLP. It was even more pronounced than in
      severe congenital neutropenia (SCN). However, [Ca2+]i fluxes were normal when
      ionomycin was used. Neutrophils from patients with cyclic neutropenia (cyNP) and
      chemotherapy-induced neutropenia (chNP) mobilized [Ca2+]i similar to those from
      healthy donors. Furthermore, we found a decreased percentage of neutrophils
      depolarizing after stimulation with fMLP and PMA in patients with SCN, whereas
      membrane depolarization was normal in patients with chNP and cyNP. All the
      alterations found here are suggested to be caused by a partial immaturity of the
      neutrophils, although in vivo activation and a direct effect of G-CSF on myeloid
      precursors might be involved.

PMID- 7529534
TI  - Thrombin binding to platelets and their activation in plasma.
AB  - The interactions of alpha-thrombin with platelets are critical in haemostasis and
      arterial thrombosis. This study established methods for characterizing the
      binding of alpha-thrombin to platelets and some of its consequences in platelet
      rich plasma. The binding of alpha-thrombin to platelets and the subsequent
      platelet activation were quantified by flow cytometry, using affinity purified
      polyclonal antibodies to human alpha-thrombin and a monoclonal antibody to GMP
      140, respectively. Dose-dependent binding of alpha-thrombin to platelets and
      their activation occurred in parallel, both reaching the maxima for each enzyme
      concentration within 10s after > or = 1.0 nM alpha-thrombin was added to
      recalcified PRP containing 1 microM recombinant tick anticoagulant peptide. The
      tick anticoagulant peptide abrogated prothrombin activation in the platelet-rich
      plasma. alpha-Thrombin binding to platelets, and their activation, were abrogated
      by a monoclonal antibody to the hirudin tail-like domain of the seven
      transmembrane thrombin receptor on platelets. Therefore this receptor represents
      an important site for alpha-thrombin binding to platelets suspended in plasma. D
      Phe-Pro-ArgCH2-alpha-thrombin only bound to platelets when its concentration was
      > or = 100 nM, and it did so without inhibiting platelet activation by alpha
      thrombin. Whereas concentrations of hirudin equimolar to those of alpha-thrombin
      failed to abrogate alpha-thrombin-mediated activation of platelets, a 10-fold
      molar excesses of hirudin over alpha-thrombin abrogated alpha-thrombin binding to
      platelets. The demonstration that > or = 1.0 nM alpha-thrombin can bind to
      platelets and initiate their activation raises the possibility that the levels of
      thrombin generated in venous and arterial thrombosis contribute to platelet
      activation in vivo.

PMID- 7529530
TI  - Polycythaemia vera. IV. Specific binding of stem cell factor to normal and
      polycythaemia vera highly purified erythroid progenitor cells.
AB  - Polycythaemia vera (PV) patients' blood burst-forming units-erythroid (BFU-E)
      have an enhanced sensitivity to stem cell factor (SCF) compared to normal BFU-E.
      To characterize SCF receptors on erythroid progenitors from normal individuals
      and PV patients, we performed binding experiments using radioiodinated
      recombinant SCF (rSCF), day 1 BFU-E and day 8 erythroid colony-forming cells
      (ECFC), which are mostly colony-forming units-erythroid (CFU-E). 125I-rSCF binds
      to a single class of cell surface receptors (23,000/ECFC) at 0 degrees C with a
      high-binding affinity (Kd = 17 pM). Saturation occurred at 0.5 nM (10 ng/ml)
      which produces a nearly maximum biological effect. One half of the radiolabelled
      rSCF was internalized by the cells after 30 min at 37 degrees C. No significant
      differences in the receptor number, dissociation constant, or internalization
      rate were found between normal and PV ECFC. Autoradiographic analysis of 125I
      rSCF binding to normal BFU-E and ECFC showed that no differences were present in
      either the percentage of positive cells or the number of radioactive grains/cell
      between the normal and PV erythroid progenitors. The enhanced sensitivity of PV
      BFU-E and CFU-E to SCF does not appear to be related to changes in SCF receptor
      number, binding affinity or internalization and the hypersensitivity of PV
      erythroid progenitors to SCF must reside in a further internal cellular
      abnormality.

PMID- 7529535
TI  - Use of G-CSF alone to mobilize peripheral blood stem cells for collection from
      children.
AB  - We report the data of 19 children with neuroblastoma (NB) or Ewing's sarcoma (EW)
      who had peripheral blood stem cells (PBSCs) harvested after mobilization by: (1)
      cyclophosphamide (CY) + etoposide + G-CSF, (2) CY + GM-CSF, or (3) G-CSF alone.
      There were no consistent differences in the number of PBSCs collected following
      these three different mobilization regimens as assessed by CFU-GM. 17 patients
      were reinfused with PBSCs after myeloablative therapy and had successful
      haemopoietic recovery. These results show that in children with solid tumours
      such as NB or EW a sufficient number of PBSCs can be collected after G-CSF alone,
      and that PBSCs collected following stimulation by G-CSF alone are as effective in
      reconstituting haemopoiesis as those collected after mobilizing chemotherapy +
      HGFs.

PMID- 7529537
TI  - Protective effect of granulocyte-colony stimulating factor against amphotericin B
      induced myelosuppression in vitro.
AB  - Amphotericin B causes suppression of bone marrow (BM) progenitor cells in vitro.
      Granulocyte colony stimulating factor (G-CSF) enhances the proliferation of
      myeloid cells. The present study defines the role of G-CSF in preventing
      amphotericin B-induced myelosuppression. G-CSF increased the proliferative
      potential of BM and protected against amphotericin B-induced myelosuppression if
      it was added to the medium during the early phase of exposure of BM to
      amphotericin B. Monoclonal antibodies to tumour necrosis factor-alpha (TNF) or
      interferon-gamma (IFN) inhibited the myelosuppression partially; simultaneous
      presence of both these antibodies completely abrogated this suppression,
      suggesting that both TNF alpha and IFN gamma were involved in amphotericin
      induced myelosuppression. TNF- or IFN-induced suppression of BM was also
      inhibited by G-CSF. These data suggest that G-CSF prevents the amphotericin B
      induced myelosuppression by antagonizing the suppressive effects of TNF and IFN
      and by enhancing the proliferative activity of BM.

PMID- 7529538
TI  - Effects of rhG-CSF, 5-fluorouracil and extramedullary irradiation on murine
      megakaryocytopoiesis in vivo.
AB  - The aim of this study was to systematically characterize possible rhG-CSF effects
      on the murine megakaryocyte-platelet system (untreated and recovering from
      chemotherapy or extramedullary irradiation). In untreated, splenectomized male
      B6D2F1 mice, rhG-CSF treatment (50 micrograms/kg/d for up to 8 d) markedly
      decreased femoral megakaryocytopoiesis. CFU-Meg, small acetylcholinesterase
      positive (SAChE) cells, and megakaryocytes were significantly reduced to 35-70%;
      platelets, however, were not affected. Peripheral CFU-Meg and CFU-GM increased up
      to 200-fold. Following a single injection of 5-FU (150 mg/kg) on day 0, rhG-CSF
      (50 micrograms/kg/d) on days 1-8 suppressed the megakaryocytopoietic recovery as
      indicated by significantly lower platelet numbers on day 9. Granulopoietic
      recovery was accelerated by rhG-CSF. When rhG-CSF treatment was started on day 5,
      no beneficial effect on granulopoietic recovery was observed, but again platelet
      levels were significantly lower on day 9, indicating that within the first 4 d of
      rhG-CSF application, recruitment or lineage competition was not a critical event.
      To test for the effects of extramedullary irradiation on circulating progenitors,
      mice pretreated with 50 micrograms/kg/d of rhG-CSF for 8 d received irradiation
      to the chest with 500 cGy resulting in a substantial kill of circulating CFU-Meg
      and CFU-GM of up to 99%. However, this striking decrease of blood progenitors did
      not significantly affect their total body contents. This study indicates that rhG
      CSF treatment can impair bone marrow megakaryocytopoiesis, which might be an
      important consideration for those clinical situations that carry a high potential
      for treatment-induced thrombocytopenia.

PMID- 7529539
TI  - Long-term safety of treatment with recombinant human granulocyte colony
      stimulating factor (r-metHuG-CSF) in patients with severe congenital
      neutropenias.
AB  - Congenital neutropenias include a heterogenous group of diseases characterized by
      a decrease in circulating neutrophils. In phase I/II/III studies in patients with
      severe congenital and cyclic neutropenia, treatment with recombinant human
      granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the
      absolute neutrophil counts (ANC) and a reduction in infections. We report the
      effects of long-term safety of subcutaneous r-metHuG-CSF administration in 54
      patients (congenital n = 44. cyclic n = 10) treated for 4-6 years. A sustained
      ANC response was seen in 40/44 severe congenital neutropenia patients and 10/10
      cyclic neutropenia patients. Two patients required an increase of > 25% in dose
      to maintain a clinical response; one patient became refractory to therapy. A
      significant decrease in the incidence of severe infections and the need for
      intravenous antibiotics was noted. Significant adverse events noted which may or
      may not be related to therapy included: osteopenia (n = 15), splenomegaly (n =
      12), hypersplenism (n = 1), vasculitis (n = 2), glomerulonephritis (n = 1), BM
      fibrosis (n = 2), MDS/leukaemia (n = 3), and transient inverted chromosome 5q
      with excess blasts (n = 1). R-metHuG-CSF has been well tolerated in the majority
      of patients and resulted in a long-term improvement in their clinical status.

PMID- 7529536
TI  - A flow cytometric assay of CD34-positive cell populations in the bone marrow.
AB  - CD34+ BM cells form a heterogenous population of primitive stem cells and more
      mature progenitors committed to different lineages of differentiation. By
      combining CD45 expression with SSC, it is possible to separate immature cells
      from more differentiated BM cells, and, by three-colour flow cytometry, analyse
      the antigens expressed in various subsets of cells. In this paper we show that in
      the normal BM at least four distinct CD34+ cell populations can be identified by
      their different patterns of CD45 expression and SSC. The most immature CD34+ cell
      population (0.1% of the BM cellularity) lacked all signs of lineage commitment
      and was CD45RA negative and only weakly CD45 positive. With increasing expression
      of the CD45 antigens, a second CD34+ population (0.2% of the BM cellularity) was
      formed expressing mainly primitive lymphatic antigens. However, 30% of the cells
      co-expressed B-cell line antigens and myeloid antigens. Cells committed to the
      myeloid cell line lost B-cell line antigens, gained CD45 antigen expression and
      SSC and formed two CD34+ cell populations (0.2% and 0.1% of the BM cellularity,
      respectively) differing only with respect to the pattern of myeloid antigen
      expression and SSC characteristics. Similarly, differentiation along the
      lymphatic pathway implicated down-regulation of myeloid antigens, loss of the
      stem cell antigen and immature lymphatic antigens and gain of CD45 expression and
      mature lymphatic antigens.

PMID- 7529541
TI  - Pentosan-induced thrombocytopenia: support for an immune complex mechanism.
AB  - Pentosan polysulphate is a low molecular weight heparinoid that is used as an
      anticoagulant. Because the drug also has antineoplastic properties, it has been
      used experimentally at the National Institutes of Health to treat metastatic
      malignancies. We present the case of a patient who developed thrombocytopenia
      resembling Type II heparin-induced thrombocytopenia (HIT) during the course of
      pentosan therapy. The patient's plasma demonstrated platelet reactivity both by
      aggregometry and 14C-serotonin release in the presence of pentosan. Heparin and
      other polyanions could substitute for pentosan in aggregation studies. The
      aggregating activity co-purified with the patient's IgG and was inhibited by pre
      incubation with monoclonal antibody (MoAb) to the platelet Fc receptor. To
      elucidate the relationship between the platelet, the polyanion and the antibody,
      we measured the binding of 3H-heparin to platelets in the presence of the
      patient's IgG and found that it was increased 6-fold over binding in the presence
      of control IgG. Heparin binding was not reduced by MoAb against the Fc receptor.
      Taken together, these data support a model in which polyanion-antibody complexes
      attach to the platelet surface by the polyanion and secondarily stimulate the
      platelet via their Fc termini.

PMID- 7529540
TI  - Expression and functional role of c-kit ligand (SCF) in human multiple myeloma
      cells.
AB  - In this study we investigated the proliferation of three well-documented MM lines
      and 10 bone marrow samples from myeloma patients in response to rh-SCF alone and
      combined with Interleukin-6 (IL-6), IL-3 and IL-3/GM-CSF fusion protein PIXY 321.
      Neoplastic plasma cells were highly purified (> 90%) by immunomagnetic depletion
      of T, myeloid, monocytoid and NK cells. The number of S-phase cells was evaluated
      after 3 and 7 d of liquid culture by the bromodeoxyuridine (BRDU) incorporation
      assay. The proliferation of RPMI 8226 and U266 cell lines was also assessed by a
      clonogenic assay. All the experiments were performed in serum-free conditions.
      RPMI 8226 cell line was not stimulated by SCF which also did not augment the
      proliferative activity of IL-6, IL-3 and PIXY-321. Conversely, SCF addition
      resulted in 2.4-fold increase of the number of U266 colonies and in a higher
      number of U266 and MT3 cells in S-phase (24.5 +/- 2% SEM v 14.5 +/- 1% SEM and 32
      +/- 3% SEM v 21 +/- 4% SEM, respectively; P < 0.05). The c-kit ligand also
      enhanced the proliferation of MT3 and U266 cells mediated by the other cytokines.
      Anti-SCF polyclonal antibodies completely abrogated the proliferative response of
      MT3 cells to exogenous SCF and markedly reduced the spontaneous growth of the
      same cell line. Reverse transcriptase-polymerase chain reaction amplification (RT
      PCR) did detect SCF mRNA in MT3 and RPMI 8226 cells. Moreover, secreted SCF was
      found, in a biologically active form, in the supernatant of the two cell lines by
      the MO7e proliferation assay. When tested on fresh myeloma samples, SCF increased
      the number of S-phase plasma cells (4.7 +/- 1.6% v 3.4 +/- 1.3% in control
      cultures: P = 0.02). Significant proliferation was also induced by IL-6 (7 +/-
      2.3% of BRDU+ cells; P = 0.006), IL-3 (5.3 +/- 1.3%; P = 0.01) and PIXY-321 (5.4
      +/- 1.6%; P = 0.02). The addition of SCF significantly enhanced the proliferation
      of myeloma cells responsive to IL-6. In summary, our results indicate that SCF is
      expressed in MM cells and stimulates the proliferation of neoplastic plasma
      cells.

PMID- 7529542
TI  - Cyclic thrombocytopenia associated with IgM anti-GPIIb-IIIa autoantibodies.
AB  - We studied a female patient with cyclic fluctuation in platelet count following
      splenectomy for autoimmune thrombocytopenia. The cyclical fluctuation appeared to
      be in phase with her menstrual cycle and her platelet count was low during
      menses. Bone marrow examinations performed at the peak as well as the bottom of
      the platelet count showed normal or increased numbers of megakaryocytes. The
      patient's platelet count increased rapidly after intravenous gamma-globulin
      (IVIgG) therapy, suggesting that a failure of platelet production is unlikely to
      account for the cycle. Platelet-associated IgM (PAIgM) was markedly elevated,
      whereas PAIgG was normal at any stage of the cycle. MACE assay demonstrated that
      PAIgM contained IgM anti-glycoprotein (GP) IIb-IIIa autoantibodies. Comparison
      between MACE assay using untreated and EDTA-treated platelets at 37 degrees C
      demonstrated that the platelet-associated IgM autoantibodies mainly recognized
      divalent cation-dependent conformation(s) of GPIIb-IIIa. No antibodies were,
      however, detected in her serum. The levels of IgM anti-GPIIb-IIIa showed an
      inverse relationship with the platelet count. In spite of the marked increase in
      platelet count after IVIgG, however, the levels of IgM anti-GPIIb-IIIa remained
      elevated. These findings suggest that platelet-associated IgM anti-GPIIb-IIIa
      autoantibodies are of pathogenic significance in this patient.

PMID- 7529544
TI  - Anti-CD36 antibodies in patients with lupus anticoagulant and thrombotic
      complications.
AB  - Six patients with lupus anticoagulant with thrombotic complications, but not
      exhibiting systemic lupus erythematosus, demonstrated the presence in their
      plasma of antibodies directed against platelet antigens which were not detectable
      in two patients presenting with lupus anticoagulant but without thrombotic
      complications. Protein blotting of separated normal platelet proteins against
      patient plasma gave up to 18 bands of varying intensity indicative of multiple
      antiplatelet antibodies; one of these antibodies recognized a component with a
      mobility identical with CD36 (GPIV; m.w. 88,000) in 4/6 cases. Antibodies to CD36
      and one or two other components were identified in 5/6 cases by
      immunoprecipitation from 125I-labelled control platelets and 6/6 by dot blots
      against purified CD36. These results suggest that antiplatelet antibodies and,
      specifically, anti CD36 antibodies, occur frequently in the plasma of patients
      presenting with lupus anticoagulant and thrombotic complications.

PMID- 7529546
TI  - A semi-automated micro-method for the histological assessment of fat embolism.
AB  - A method of quantitatively determining the volume of fat emboli in a tissue using
      an image analysis system (I.B.A.S.) was developed. This procedure is an
      interactive, semi-automated tool allowing the quick and accurate gathering of
      large quantities of data from sections of different tissue samples stained by
      osmium tetroxide. The development of this procedure was aimed at producing a
      system which is reliable, reproducible and semi-automated thereby enabling
      epidemiological and serial studies to be made of a large number of histological
      sections from different tissues. The system was tested in a study of tissue
      sections from a series of fatalities from an aircraft crash in an attempt at
      correlating the incidence of fat emboli with the presence of multiple fractures
      and soft tissue injuries, the correlation to be made being between the
      quantitative presence of fat emboli and the extent and severity of injuries
      suffered.

PMID- 7529545
TI  - Histological and enzyme histochemical parameters for the age estimation of human
      skin wounds.
AB  - Routine histological staining techniques form the basis of a forensic age
      estimation of human skin wounds and the determination of vitality is aided by the
      detection of neutrophilic granulocytes which appear earliest about 20-30 min
      after wounding. A clear granulocyte infiltration and a significant increase in
      the number of macrophages indicates a post infliction interval of at least
      several hours. Macrophages containing incorporated particles such as lipophages,
      erythrophages or siderophages appear earliest at a wound age of 2-3 days
      similarly to extracellular deposits of hemosiderin, whereas the rarely detectable
      iron-free pigment hematoidin and spot-like lymphocytic infiltrates in the
      granulation tissue appear approximately one week or more after wounding. A
      complete reepithelialization of surgically treated and primarily healing human
      skin lesions can be expected earliest 5 days after wound infliction and the
      absence of a complete new epidermal layer indicates a survival time of less than
      21 days. Enzyme histochemical methods allow a wound age differentiation
      especially in the range of a few hours. An increase in nonspecific esterases can
      be observed earliest approximately 1 hour after wounding followed by other
      enzymes such as acid phosphatase (approximately 2 h), ATPase (approximately 4 h),
      aminopeptidase (approximately 4 h) or alkaline phosphatase (approximately 4 h).
      Positive results, however, cannot be regularly found. Therefore, the detection of
      reactive changes is useful for a wound age estimation whereas negative findings,
      which in general must be interpreted with caution, can provide information only
      in a limited number of histological parameters.

PMID- 7529547
TI  - Identification, molecular cloning, and characterization of the chromosome 12
      breakpoint cluster region of uterine leiomyomas.
AB  - Recent molecular cytogenetic analysis of uterine leiomyoma cell lines with
      chromosome 12 aberrations has indicated that their chromosome 12 breakpoints map
      between linkage locus D12S8 and the CHOP gene. Here, we report fluorescence in
      situ hybridization (FISH) and molecular cloning studies of the chromosome 12
      breakpoints in a panel of seven such uterine leiomyoma cell lines; five with the
      frequently observed t(12;14)(q15;q24), one with t(12;15)(q15;q24), and one with
      ins(12;11)(q14;q21qter). Directional chromosome walking studies starting from
      D12S8 and the CHOP gene resulted in the isolation of a relatively large number of
      overlapping YAC clones, including Y5355 (465 kbp), Y7673 (360 kbp), and Y9899
      (275 kbp). In total, the inserts of these three YAC clones span an 800 kbp long
      and presumably contiguous stretch of human genomic DNA. All chromosome 12
      breakpoints of the uterine leiomyoma cell lines studied were found by FISH
      analysis to be mapping within a 445 kbp subfragment of this region and,
      furthermore, to be dispersed over a DNA region which is at least 150 kbp in size.
      The chromosome 12 breakpoint of t(12;14)(q15;q24) in uterine leiomyoma cell line
      LM-30.1/SV40 was tentatively mapped within the 60 kbp region between YAC clones
      Y9899 and Y5355. From this 60 kbp region and close to sequence-tagged site RM99,
      we isolated probe pRM118-A, which showed in Southern blot analysis that it
      detected a rearrangement in LM-30.1/SV40 DNA, and generated restriction maps of
      the normal and rearranged genomic DNA regions detected with this probe. Finally,
      we molecularly cloned part of one of those rearranged DNA fragments using a
      vectorette-PCR-based technique and demonstrated that it consisted of 12q13-q15
      sequences fused to DNA sequences derived from 14q23-24 and most likely
      represented the translocation junction on der(14) in LM-30.1/SV40 cells. Our
      studies strongly suggest that we have identified and isolated the uterine
      leiomyoma cluster region of chromosome 12 breakpoints, which we designate ULCR12,
      and molecularly cloned and characterized the der(14) translocation junction in
      cells derived from a uterine leiomyoma carrying the frequently observed
      t(12;14)(q15;q24).

PMID- 7529548
TI  - Genetic alterations in localized prostate cancer: identification of a common
      region of deletion on chromosome arm 18q.
AB  - Accumulation of mutations in oncogenes and tumor suppressor genes transforms a
      normal cell into a malignant cell by allowing it to escape from normal control of
      growth. In prostate tumorigenesis, the current model envisages specific mutations
      of the TP53 tumor suppressor gene and loss of loci, detected by loss of
      heterozygosity (LOH), on chromosome arms 8p, 10q, 16q, and 18q. In order to
      determine if alterations frequently found in other adenocarcinomas (breast,
      ovarian, gastric, colorectal), including losses of genetic material from
      chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in
      prostate cancer, we examined 20 localized early-stage prostate tumors. We
      detected no mutations of the TP53 gene. Allelic losses were found from 7q (33%),
      8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward
      isolating tumor suppressor genes on 18q, we used six polymorphic markers and
      identified a small common deleted region between the chromosome 18 centromere and
      the D18S19 locus.

PMID- 7529549
TI  - Origin and biology of a testicular Wilms' tumor.
AB  - A pure triphasic testicular Wilms' tumor, without teratomatous elements, was
      studied using multiple techniques. Carcinoma in situ (CIS), the characteristic
      precursor of testicular germ cell tumors of adults (TGCTs), was found in the
      adjacent parenchyma. Flow cytometric analysis showed a single hypotriploid tumor
      stem line. Karyotyping of the tumor revealed some numerical and structural
      abnormalities, including an i(12p), the chromosomal marker of TGCTs. In situ
      hybridization supported the karyotypic findings, and showed a similar numerical
      distribution in CIS and the tumor. Molecular analysis of the tumor illustrated
      that all short arms of chromosome 12, including i(12p), were of maternal origin.
      No 12q deletions were detected. In spite of complete loss of the paternal 11p13
      band, the zinc finger regions and exons 2 and 6 of the WT1 gene contained no
      aberrations. Therefore, this tumor suppressor gene is not inactivated due to
      aberrations in the studied regions. In addition, all four WT1 alternative
      transcripts were expressed in the tumor. No aberrations were found in chromosomal
      bands 11p15.5, 16q22.1, and 16q24. Both parental alleles of the human imprinted
      genes H19 and IGF2 were expressed in the tumor. This is the first report on the
      chromosomal and molecular characterization of an extrarenal Wilms' tumor. Its
      germ cell origin was unequivocally demonstrated.

PMID- 7529543
TI  - Anti-CD36 antibodies in thrombotic thrombocytopenic purpura.
AB  - The membrane glycoprotein CD36 (GPIV, M(r) 88,000) is found on platelets,
      monocytes and endothelial cells of the microvasculature. In the present study,
      anti CD36 antibodies have been identified as occurring with high frequency in
      patients with thrombotic thrombocytopenic purpura. The presence of anti CD36
      antibodies in 15 TTP plasma samples thought to contain them on the basis of an
      initial screening by protein blots was confirmed by re-screening against a
      standard of purified CD36, by immunoprecipitation from 125I-labelled control
      platelets and by dot blots against purified CD36. In a further 28 random samples
      examined, 23/27 (85%) were CD36-positive by immunoprecipitation, 21/28 (75%) by
      protein blotting, and 17/28 (60%) by dot blots against purified CD36. On protein
      blots following SDS-PAGE, immunoprecipitates produced from normal platelets by
      TTP plasma gave positive reactions with the anti CD36 monoclonal antibody 125I
      Mo91. One half of the total TTP samples examined (21/42) caused approximately 70%
      release in control platelets loaded with 14C-serotonin. Of samples causing
      release > or = 70%, one-half (8/15) failed to cause release from Naka-negative
      platelets which constitutively lack CD36 showing that CD36 was the sole target
      for platelet activation in these TTP samples. These studies demonstrate that
      antibodies directed against CD36 occur frequently in TTP patients and could cause
      thrombotic complications and vascular damage by reacting with the parent antigen
      present in platelets and endothelial cells.

PMID- 7529551
TI  - Allelotype of head and neck paragangliomas: allelic imbalance is confined to the
      long arm of chromosome 11, the site of the predisposing locus PGL.
AB  - Paragangliomas of the head and neck region are usually slow growing, benign
      tumors. A considerable fraction has a positive family history, and the
      predisposing locus, PGL, has recently been assigned to 11q22-q23. The inheritance
      pattern of the disease suggests that PGL undergoes maternal genomic imprinting.
      We have investigated 26 tumor samples from 22 patients with head and neck
      paragangliomas for the occurrence of loss of heterozygosity (LOH) on all non
      acrocentric autosome arms. LOH was found only on chromosome 11, with a marked
      clustering on the distal half of the q-arm. However, in many cases the resulting
      allelic imbalance relative to normal DNA was weak, suggesting that only part of
      the tumor showed this abnormality. In all eight cases where we were able to
      determine the parental origin, the allele undergoing loss was maternally derived.
      Clonality analysis with a polymorphic marker for the X-chromosome indicated that
      two of three informative female cases were polyclonal, although a number of
      tumors carry aneuploid stemlines in DNA flow cytometry. We conclude that either
      tumor heterogeneity or polyclonality may explain the partial allele loss events
      seen in certain cases.

PMID- 7529550
TI  - Acute myelomonocytic leukemia with t(10;11)(p13;q23): heterogeneity of
      breakpoints at 11q23 and association with recombinase activation.
AB  - The human trithorax homolog gene (MLL) is directly involved in over 90% of cases
      of acute leukemia with abnormalities of 11q23. However, involvement of other
      genes at 11q23 both centromeric and telomeric of MLL has been identified in
      different subtypes of leukemia and lymphoma. We describe a case of acute
      myelomonocytic leukemia (AMML; FAB type M4) with t(10;11)(p13;q23) in which the
      breakpoint at 11q23 was centromeric to the MLL gene and distinct from the
      breakpoint seen in promyelocytic leukemias with t(11;17)(q23;q22), thus providing
      further evidence of heterogeneity of breakpoints in 11q23 in acute leukemia.
      Rearrangements of immunoglobulin (IG) and T-cell receptor (TCR) genes were also
      observed, with no immunophenotypic evidence for commitment to the lymphoid
      lineages, indicating that inappropriate activation of the recombinases may be a
      feature of this particular variant translocation.

PMID- 7529552
TI  - Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line
      identify a new member of the forkhead gene family.
AB  - Chromosome translocations involving 11q23 are associated with a number of
      different types of leukemia. These translocations fuse a gene encoding a putative
      transcription factor, HTRXI, to genes on other chromosomes. We report cloning and
      sequencing the t(X;11) breakpoint region from a cell line established from an
      infant with acute lymphocytic leukemia. The gene AFXI, on the X chromosome, is
      expressed in a variety of cell types. Sequence analysis indicates a high degree
      of homology between AFXI and the forkhead family of transcription factors. The
      high degree of identity within the forkhead region and the lack of homology
      outside that region suggest that AFXI represents a novel forkhead family member.
      It is predicted that a chimeric fusion protein with altered DNA binding activity
      will be the result of the translocation.

PMID- 7529553
TI  - Juxtaposition of N-myc and Ig kappa through a reciprocal t(6;12) translocation in
      a mouse plasmacytoma.
AB  - Nearly all mouse plasmacytomas (MPCs) carry an Ig/myc translocation. Any one of
      the three Ig loci may participate, while the myc contribution has been limited to
      c-myc, excluding other members of the myc gene family. The same is true for the
      other two known Ig/myc translocation-carrying tumors, Burkitt's lymphoma and rat
      immunocytoma. It is believed that the Ig/myc juxtaposition plays a decisive, rate
      limiting role in the genesis of the three tumors, acting through the constitutive
      activation of myc that makes it refractory to normal regulation. Here we describe
      the molecular analysis of a unique t(6;12)(CI;B) translocation that we previously
      identified in an exceptional MPC that expressed N-myc but not c-myc. We now show
      that the translocation led to the juxtaposition of N-myc and Ig kappa. This is
      the first case of an Ig/myc-carrying tumor that involves N-myc rather than c-myc.
      These findings suggest that the translocation may already have occurred at the
      pro- or pre-B cell stage at which N-myc is open for transcription. According to
      this interpretation, constitutive activation of N-myc would suppress the
      expression of c-myc, but would not interfere with the differentiation of the pro
      B cell into a fully mature plasma cell. Its tumorigenic influence would become
      manifest only at the time when the cell would normally be programmed to leave the
      cycling compartment, in connection with its terminal differentiation.

PMID- 7529555
TI  - Localization of Beckwith-Wiedemann and rhabdoid tumor chromosome rearrangements
      to a defined interval in chromosome band 11p15.5.
AB  - Chromosome rearrangements have provided useful landmarks to identify disease loci
      and have served as starting points for positional cloning strategies for
      candidate genes. We have used fluorescence in situ hybridization (FISH) and
      pulsed-field gel electrophoresis (PFGE) to map three Beckwith-Wiedemann syndrome
      (BWS) breakpoints and a rhabdoid tumor breakpoint more precisely. These
      breakpoints mapped to the interval between D11S679 and the insulin-like growth
      factor 2 (IGF2) gene on 11p15.5. A cosmid (c15-2) was identified that mapped
      centromeric to the BWS t(11;16) and the rhabdoid tumor-associated t(11;22),
      telomeric to the BWS t(11;22), and was found to span the BWS-associated inv(11)
      breakpoint. Pulsed-field gel analysis placed all four breakpoints into a 250-675
      kb interval distal to D11S679 and at least 270 kb centromeric to the IGF2 and H19
      loci. These data locate all three BWS rearrangements and the rhabdoid tumor
      t(11;22) breakpoint in the same region of 11p15.5, suggesting that they may be
      affecting the same locus or closely linked loci. Cosmid c15-2 provides a well
      defined starting point in the search for candidate disease genes.

PMID- 7529554
TI  - Analysis of glioma cell lines for amplification and overexpression of MDM2.
AB  - Recently, amplification of the gene encoding a p53 binding protein, MDM2, was
      determined in 8% of the cases constituting a large series of glioblastomas. Here
      we have utilized Southern blot analysis to examine 30 cell lines established from
      such tumors, and our investigation has revealed large increases in MDM2 gene
      dosage in two cases, one of which showed coamplification of the CDK4 gene that
      resides in close proximity to MDM2 in chromosomal region 12q13-14. Northern
      analysis demonstrated overexpression of MDM2 mRNA in the two cell lines with gene
      amplification, and overexpression of MDM2 protein was evident in each of these by
      immunohistochemical and Western blot analysis. Analysis of TP53 cDNAs revealed
      normal TP53 sequences in the cell lines with MDM2 amplification; these results
      are consistent with those of previous studies suggesting that MDM2 amplification
      occurs only in tumors expressing wild-type p53. In total, these data suggest that
      MDM2 amplification in glioblastoma cell lines occurs at a frequency (6.7%)
      comparable to that determined in primary tumors; occurs in cell lines expressing
      wild-type p53; and can involve the coamplification of additional genes.

PMID- 7529556
TI  - Natural killer cells recognize common antigenic motifs shared by H-2Dd, H-2Ld and
      possibly H-2Dr molecules expressed on bone marrow cells.
AB  - Murine natural killer (NK) cells can mediate specific rejection of bone marrow
      cell (BMC) allografts. Whereas positive recognition of allogeneic MHC antigens
      forms the basis for T cell alloreactivity, it has been postulated that NK cells
      are reactive against targets that do not express certain self-encoded MHC class I
      antigens. Here, we study the immunogenicity of BMC grafts from two class I
      transgenic mice, D8 (B6 mice with an H-2Dd transgene) and C3H.Ld (C3H mice with
      an H-2Ld transgene). D8 BMC grafts are acutely rejected by B6 but not D8
      recipients. This suggests that antigenic motifs associated with the H-2Dd
      molecule are recognized. B6 mice depleted of their CD3+ but not NK1.1+ cells can
      still reject D8 BMC grafts. These data suggest that NK1.1+/CD3- cells recognize
      the H-2Dd derived antigenic motifs. Similarly, C3H.Ld BMC grafts are rejected by
      B6 x C3H F1 but not B6 x C3H.Ld F1 recipients. Thus, antigenic motifs associated
      with the H-2Ld molecule can also be recognized. Furthermore, expression of either
      H-2Dd or H-2Ld by the recipients renders them unable to reject D8 or C3H.Ld BMC
      grafts. Therefore, H-2Dd and H-2Ld molecules appear to express common antigenic
      motifs recognized by NK cells. Additional studies with B6.R4 (KbIbSbDr), an intra
      H-2 recombinant mouse, indicated that a third class I molecule, possibly H-2Dr,
      also shared the common antigenic motifs with both H-2Dd and H-2Ld molecules.
      Thus, positive recognition of class I antigens by NK cells can occur. However,
      expression of some of these antigenic motifs appear to be negatively controlled
      by certain H-2r genes as suggested by rejection of D8 and B6.R4 BMC grafts by D8
      x B10.RIII F1 and B6.R4 x B10.RIII F1 hybrids respectively.

PMID- 7529557
TI  - DRAWNA: a program for drawing schematic views of nucleic acids.
AB  - A program for drawing automatically exact and schematic views of nucleic acids is
      described. The program is written in C ANSI and uses the Silicon Graphics GL and
      Xirisw libraries within the X11/Motif environment. Through menus, the user can
      choose, specify, and manipulate in real time the three-dimensional views to be
      displayed. Drawing options include partitioning of structures into differently
      colored or shaped fragments, representation of backbones as flat or with conic
      section ribbons, display of paired or free bases as rods, and display of surfaces
      as filled or outlined and stereo or depth-cued views.

PMID- 7529559
TI  - Ribosomal components neighboring the 2475 loop in Escherichia coli 50S subunits.
AB  - We report the synthesis of a radioactive, photolabile oligodeoxyribonucleotide
      probe and its exploitation in identifying 50S ribosomal subunit components
      neighboring its target site in 23S rRNA. The probe is complementary to 23S rRNA
      nucleotides 2475-2483, a single-stranded sequence (the 2475 loop) near the
      peptidyltransferase center of Escherichia coli ribosomes. On photolysis in the
      presence of 50S subunits, it site-specifically incorporates into proteins L1,
      L13, L16, L32, and L33 and into 23S rRNA nucleotides G2470, A2471, and G2472.
      These results provide clear evidence that C2475 in 23S rRNA is within 21 A (the
      distance between C2475 and the photogenerated nitrene) of proteins L1, L13, L16,
      L32, and L33. The implications of these results for the evolving model of the
      internal structure of the 50S subunit are considered.

PMID- 7529560
TI  - An inhibitor of ribosomal peptidyl transferase using transition-state analogy.
AB  - The phosphoramidate of CCdAp and puromycin (CCdApPuro) is a potent inhibitor of
      ribosomal peptidyl transferase, as assayed by the fragment reaction. Inhibition
      is competitive at the ribosomal A-site. CCdApPuro protects P-site-associated
      bases in the peptidyl transferase loop region of 23S rRNA from carbodiimide
      modification. The Ki's of structural homologues of CCdApPuro suggest that both
      the CCdA and puromycin moieties participate in binding. Thus, CCdApPuro appears
      to bridge the A- and P-sites of the ribosome, implying that substrates are
      juxtaposed with a geometry suitable for direct reaction during peptidyl transfer.

PMID- 7529561
TI  - The S4 segment and gating of voltage-dependent cationic channels.

PMID- 7529558
TI  - S-antigen specific T cell clones from a patient with Behcet's disease.
AB  - The isolation and characterisation of T cell clones or lines specific to retinal
      antigens are valuable tools to clarify the underlying mechanisms of autoimmunity
      to retinal antigens as a contributing factor in ocular inflammation. Patients
      with Behcet's disease have been reported to be sensitised to S-antigen (S-Ag). In
      the present study, four T cell clones established from the peripheral blood of a
      patient with Behcet's disease were analysed. A CD4+ T cell clone (clone 2) and a
      CD8+ T cell clone (clone 10) proliferated specifically to bovine S-Ag. Although
      these S-Ag specific T cell clones proliferated vigorously to the intact antigen,
      their responses to S-Ag derived synthetic peptides M and G were weak, suggesting
      that the sites of human T cell recognition of S-Ag may be different from those
      established in the experimental model. The proliferative responses of both clones
      (2 and 10) were inhibited by anti-HLA-DR monoclonal antibody but not by anti-HLA
      class 1 monoclonal antibody. The other two clones studied, clones 6 and 30, were
      CD3+, CD4-, CD8-, and they did not proliferate specifically to S-Ag. Clone 6
      expressed gamma delta T cell receptors (TCR) and showed non-specific cytotoxic
      activity toward K562 and Daudi cell lines. Clone 30 expressed alpha beta TCR, and
      was devoid of cytotoxic activity. Human T cell lines and clones specific to
      retinal antigens will provide the framework necessary to examine the events that
      lead to ocular inflammation.

PMID- 7529563
TI  - [Detection of the generation of nitric oxide from L-arginine in the murine brain
      in vivo using EPR].
AB  - Nitric oxide (NO) was shown by EPR method to be generated via L-arginine
      dependent way in brain of mice in vivo. The complexes of diethyldithiocarbamate
      (DETC) or pirrolidinedithiocarbamate (PDTC) with endogenous or exogenous Fe2+
      were used as a traps of NO, which are capable to bind NO resulted in the
      formation of mononitrosyl iron complexes with DETC or PDTC (MNIC-DETC or PDTC)
      recovered by EPR method. These complexes were detected in mouse brain in
      concentration of 2.5 nmole/g of wet tissue for 30 min only when exogenous Fe2+
      was injected in to mice. The level of MNIC-DETC (PDTC) was 5 fold increased in
      brain of mice pretreated for 4 hrs with lipopolysaccharide from Escherichia coli,
      which induced the inflammation processes. The inhibitor of NO-synthase, NG-nitro
      L-arginine attenuated the formation of MNIC-DETC (PDTC) in mouse brain in vivo.
      Exogenous Fe2+ is suggested to induced the synthesis of NO-synthase in mouse
      brain.

PMID- 7529562
TI  - Aquaporins: water selective channels in biological membranes. Molecular structure
      and tissue distribution.

PMID- 7529564
TI  - Astroglial induction of in vivo angiogenesis.
AB  - A purified population of astrocytes was prepared from embryonic rat hypothalamus.
      These cells were transplanted into the cerebral cortex of adult rats with
      survival time of 5 days and studied by glial fibrillary acidic protein (GFAP)
      immunohistochemistry and electron microscopy. A progressive gradation from the
      edges of the implant to the intact host tissue was observed in relation to the
      vascularization process. The regenerating tissue showed cells with cavities
      resembling capillary central lumens and their cytoplasms revealed gold particles
      when they were immunostained for electron microscopy. Dark processes were seen in
      capillary-like lumens and, on other occasions, evaginations of endothelial cells
      were in contact with astroglial processes. These findings lead us to suggest that
      capillary-like structures might develop from cavitated astroglial cells, which
      would permit the migration of endothelial cells into their lumens. Astroglial
      endothelial interactions persist until endothelial cells are morphologically
      differentiated. One possible interpretation of the present data is that
      astrocytes might participate directly and actively in the regulation of capillary
      formation.

PMID- 7529565
TI  - [Detection of porin in inter-mitochondrial contacts].
AB  - The binding of monoclonal antibodies (mAb) to the N-terminal part of VDAC with
      freshly isolated, unfixed rat heart mitochondria has been studied. It was
      established that mAb do not react with the main portion of the mitochondria. At
      the same time, successful binding to some of those was observed. Gold particles
      were organized, as a rule in three types of clusters: (i) thread-like clusters;
      (ii) small, irregularly shaped clusters, and (iii) big clusters covering the
      greater part of the mitochondrial surface. In the region of tight junctions
      between mitochondria, specific binding of mAb to mitochondrial VDAC, such as
      thread-like and small clusters, was found. In some cases, antibody clusters were
      localized in the region which separates two mitochondrial compartments differing
      in configuration of the cristae. When the outer mitochondrial membrane was
      partially stripped off, this membrane was extensively labelled by antibodies. It
      is concluded that the N-terminus of porin is localized on the inner surface of
      the outer mitochondrial membrane, so that some damage of the outer membrane
      appears to be required to allow the N-terminal porin antibody to contact the
      antigenic determinant. Such a damage is apparently more probable in the place of
      contacts of two mitochondria or two mitoplasts covered by the common outer
      membrane. In any case, the data obtained strongly suggest that porin is present
      in the junction region.

PMID- 7529566
TI  - [Energy-dependent Ca2+-transport in intracellular smooth muscle structures].
AB  - In experiments performed on digitonin-treated myometrium cells the existence of
      intracellular energy-dependent Ca(2+)-transporting system has been identified.
      The mitochondria-linked energy-dependent accumulation of Ca2+ was inhibited by
      ruthenium red and sodium azide with Ki of 0.7 +/- 0.3 microM and 1.1 +/- 0.4 mM,
      respectively. The Ca2+ ionophore A23187 added to the incubation medium following
      the termination of the accumulation process by ruthenium red caused a discharge
      of Ca2+ accumulated from the mitochondria. In the endoplasmic reticulum there
      exists a Mg2+,ATP-dependent Ca(2+)-pump which is potentiated by oxalate, immune
      to ruthenium red and sodium azide and inhibited by thapsigargin with Ki < 20 nM.
      In the absence of oxalate, the component of mitochondrial accumulation of Ca2+
      was 3-4 times higher that of the endoplasmic reticulum. These results indicate
      that under the conditions used the calcium capacity of mitochondria was
      significantly higher than that of the endoplasmic reticulum. It is suggested that
      mitochondria serve as a high capacity intracellular Ca(2+)-accumulating store
      protecting smooth muscle cells from Ca2+ overload under some abnormal states.
      Under normal physiological conditions the endoplasmic reticulum serves as the
      major intracellular store involved in the pharmacomechanical coupling in the
      smooth muscle of the myometrium.

PMID- 7529567
TI  - [Participation of opioid receptor of the kappa-, mu-, and delta-types in
      regulating the humoral immune response].
AB  - The alteration of opioid receptor total binding level as well as ae- and mu-,
      delta-type distribution has been investigated on the every day of primary and
      secondary immune response on bovine gamma-globulin. It has been shown that a
      level of opioid binding measured with [3H]naloxone increased by 6 times during
      the primary, and by 1.5 times during the secondary immune response on the
      antigen. A maximal value of opioid receptor activity has been observed at the 7
      th and the 5-th days correspondingly, i.e. at the peak of the response. Receptor
      activity has been measured by displacement of [3H]naloxone with corresponding
      selective opioid ligand. Growth of the quantity of ae-receptors and decrease of
      that of mu- and delta-receptor types has been found to take place starting with
      zero time till 7-th and 5-th days of response development. A reverse picture has
      been detected during the immune response falling down. Selective ae-ligand
      stimulated the secretion of specific antibodies to bovine gamma-globulin, whereas
      mu- and delta-ligands suppressed the antibody production. Functional role of
      different types of opioid peptides taking part in immune regulation is analyzed.

PMID- 7529569
TI  - Von Kossa's method for renal mineralization: application for multiple specimens
      using capillary gap technology.
AB  - Mineralization of renal tissue was investigated using Von Kossa's method and
      capillary gap technology. Combining these techniques allowed the simultaneous
      processing of 100 slides, reduced the volume of 5% silver nitrate required, and
      produced consistent dark brown to black silver deposits in positive control
      sections. A 25-fold savings in silver nitrate was achieved. By markedly reducing
      individual slide handling, technician time also was greatly reduced. Two or three
      slide sets, each containing approximately 100 slides, can be conveniently stained
      daily.

PMID- 7529568
TI  - Banding human chromosomes using a combined C-banding-fluorochrome staining
      technique.
AB  - Slides pretreated for C-banding and stained with DAPI or CMA3 show different
      banding patterns in human metaphase chromosomes compared to those obtained with
      either standard Giemsa C-banding or fluorochrome staining alone. Human
      chromosomes show C-plus DA-DAPI banding after C-banding plus DAPI and enhanced R
      banding after C-banding plus Chromomycin A3 staining. If C-banding preferentially
      removes certain classes of DNA and proteins from different chromosome domains, C
      banding pretreatment may cause a differential DNA extraction from G- and R-bands
      in human chromosomes, resulting in a preferential extraction of DNA included in G
      bands. This hypothesis is partially supported by the selective cleavage and
      removal of DNA from R-bands of restriction endonuclease HaeIII with C-banding
      combined with DAPI or Chromomycin A3 staining. Structural factors relating to
      regional differences in DNA and/or proteins could also explain these results.

PMID- 7529570
TI  - Use of the four-and-a-half clearing technique to study gymnosperm embryology:
      Cunninghamia lanceolata.
AB  - Since its introduction in 1971, the four-and-a-half clearing technique has been
      widely applied to the study of ovule and female gametophyte development in
      flowering plants as an alternative to the more arduous paraffin section methods.
      The technique has undergone several modifications that have broadened its
      application in studies of Angiosperm embryology. To date, however, the technique
      has not been successfully applied to embryological features of Gymnosperms. Dark
      coloration caused by naturally occurring substances and by-products of fixation
      render the clearing fluid ineffective, and special pretreatment methods used to
      remove dark substances in Angiosperm ovules have little or no effect on
      Gymnosperm material. In the technique reported here, paraffin sections of ovules
      and young seeds of Cunninghamia lanceolata 80-120 microns thick are cleared in
      benzyl benzoate-4 1/2 clearing fluid and examined with phase contrast optics.
      Observations of the mature female gametophyte in these cleared preparations are
      compared with those obtained from 10 microns sections, stained with safranin and
      fast green, and examined with bright-field optics. Although contrast and
      definition are more pronounced in stained sections than in cleared ones, the
      differences would not alter one's interpretation of characteristic structural
      features. The thick, cleared section offers an advantage over the thin, stained
      one in that many structural entities are contained within a single section rather
      than spread through several serial sections. The time required for clearing thick
      sections is much shorter than that required for making permanent stained
      preparations.

PMID- 7529571
TI  - Combined lectin binding and PAS/alcian blue staining in glycol methacrylate
      sections.

PMID- 7529572
TI  - Quantification of urinary catecholamines, their abundant metabolites, and 5
      hydroxyindoleacetic acid by high performance liquid chromatography and
      electrochemical detection, using a single mobile phase and uniform isocratic
      conditions.
AB  - A simple and flexible isocratic HPLC procedure was developed for the measurement
      of catecholamines and their abundant metabolites ( e.g. nor- metanephrine,
      metanephrine, methoxy-tyramine, vanillylmandelic acid, homovanillic acid) and 5
      hydroxyindolacetic acid by ion-pair reversed phase chromatography on C18 columns,
      using a single mobile phase containing both sodium octane sulphonate and
      diethylamine as ion-pairing reagents.

PMID- 7529573
TI  - Dilated cardiomyopathy: computer-assisted analysis of endomyocardial biopsy
      protein patterns by two-dimensional gel electrophoresis.
AB  - In order to identify disease-associated alterations in the myocardial protein
      patterns in dilated cardiomyopathy, we used 2-dimensional gel electrophoresis to
      analyse the proteins of endomyocardial biopsies from patients and controls.
      Proteins (150 micrograms) from biopsies (1-3 mg wet weight) were first separated
      by isoelectric focusing, then applied to large 2-dimensional gels. A computer
      assisted system (PDQUEST) was used for spot detection, quantification and
      comparison of 2-dimensional protein patterns. From a single endomyocardial biopsy
      about 1000 different protein species were resolved. The spot pattern was
      influenced by the concentration of protein during sample preparation, by the
      amount of protein loaded onto the gels and by the development time of silver
      staining. Variances of spot position in the first and second dimension and in the
      long diagonals were less than 5%. Coefficients of variance for the spot
      quantities in 8 gels were 16 +/- 8%. Contaminating blood proteins could be
      identified in the biopsy patterns. Computer-assisted comparison between
      cardiomyopathy (n = 5) and controls (n = 5) over the whole gel revealed that 55
      protein spots were increased 100%, 27 protein spots decreased 100%. Four proteins
      showed significant quantitative differences between the cardiomyopathic hearts
      and controls. Fourteen proteins were identified by amino acid analysis or
      microsequencing. An isoelectric point and molecular mass grid was laid over the
      whole gel based on these identified protein species, resulting in approximate
      isoelectric point values and molecular masses for all other protein species.
      Thus, myocardial 2-dimensional protein patterns obtained from endomyocardial
      biopsies can be used for the characterization of cardiac diseases.

PMID- 7529575
TI  - Differential regulation of gonadotropin synthesis and release in ovariectomized
      ewes after treatment with a luteinizing hormone-releasing hormone antagonist.
AB  - Our working hypothesis was that synthesis and release of LH, but not FSH, were
      solely dependent on LHRH. Twenty ovariectomized (OVX) ewes were randomly assigned
      to one of five treatments (n = 4 per group). Ewes were administered a low (10
      micrograms/kg) or high (100 micrograms/kg) dose of LHRH antagonist (LHRH-Ant) at
      24-h intervals for 3 or 6 days. Control ewes received vehicle (5% mannitol) at 24
      h intervals for 6 days. Blood samples were collected every 15 min for 4 h before
      LHRH-Ant or vehicle and every 2 h during the period of treatment to determine
      concentrations of LH and FSH. Twenty-four hours after the last treatment with
      LHRH-Ant or vehicle, anterior pituitaries were collected and divided in half
      along the midsagittal plane; the number of receptors for LHRH, pituitary content
      of LH and FSH, and relative amounts of mRNA for alpha, LH beta, and FSH beta
      subunits were determined. Concentrations of LH in serum decreased (p < 0.05) from
      25.4 +/- 4.3 ng/ml before LHRH-Ant to less than 0.5 ng/ml within 4 h after the
      first treatment of LHRH-Ant and remained low (< 0.5 ng/ml) throughout the study.
      Serum concentrations of FSH declined gradually during the 3- or 6-day period of
      treatment with LHRH-Ant, from 37.3 +/- 2.4 and 26.5 +/- 4.8 ng/ml to 19.9 +/- 1.8
      and 13.7 +/- 2.1 ng/ml, respectively. The magnitude of decline in serum
      concentrations of LH and FSH did not differ among ewes treated with low or high
      doses of LHRH-Ant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529574
TI  - Expression of two isoforms of CD44 in human endometrium.
AB  - The distribution of the cell-surface adhesion glycoprotein CD44 in human
      endometrium was examined by immunofluorescence using six monoclonal antibodies to
      epitopes common to all forms of the molecule, and by reverse transcription
      polymerase chain reaction (RT-PCR). Immunoreactivity was observed throughout the
      menstrual cycle in stroma, vessels, glandular, and luminal epithelium. Variations
      in staining intensity were observed, especially in the epithelial compartment.
      CD44 was also expressed strongly by decidualized stromal cells of first-trimester
      pregnancy. No systematic variation of immunoreactivity was observed with stages
      of the normal cycle, but a fraction (25%) of the specimens lacked reactivity in
      the epithelium. To determine the molecular size of the epithelial isoform, an
      immunoprecipitation technique was developed using surface-radioiodinated,
      detergent-extracted glands. This indicated the presence at the cell surface of a
      single dominant CD44E species with an approximate molecular mass of 130 kDa. RT
      PCR was used to investigate the isoforms present in whole endometrial tissue,
      isolated gland fragments, and Ishikawa endometrial carcinoma cells. Complementary
      DNA produced from total endometrial mRNA was PCR-amplified across the splice
      junction between exons 5 and 15. Transcripts corresponding to the hyaluronate
      receptor CD44H as well as a larger isoform were identified. CD44H was absent, or
      very scarce, in cDNA from purified gland epithelium. In contrast, Ishikawa cells
      expressed this form abundantly. The glands and Ishikawa cells also expressed
      CD44E containing sequences encoded by exons 12, 13, and 14. These data
      demonstrate the presence of CD44 in human endometrium and decidua, and show that
      different isoforms of CD44 are associated with tissue compartments in which
      different functional roles can be anticipated.

PMID- 7529576
TI  - Insulin-like growth factor-I regulation of luteinizing hormone (LH) receptor
      messenger ribonucleic acid expression and LH-stimulated signal transduction in
      rat ovarian theca-interstitial cells.
AB  - Currently available evidence supports the hypothesis that insulin-like growth
      factor-I (IGF-I) secreted by small preantral follicles may be involved in
      stimulating the initial differentiation of the theca interna and, in particular,
      expression of the LH receptor in pre-theca cells. To test this hypothesis, we
      examined the effects of IGF-I on LH receptor mRNA expression in theca
      interstitial cells (TIC) isolated from the ovaries of hypophysectomized immature
      rats by percoll gradient centrifugation. TIC (3.5 x 10(4) viable cells/well) were
      cultured up to 6 days with and without LH (0-10 ng/ml) and IGF-I (0-100 ng/ml).
      Androsterone in the medium was measured by RIA, and LH receptor mRNA was measured
      by specific reverse transcriptase-polymerase chain reaction assay. LH receptor
      mRNA was low in control (untreated) TIC. IGF-I stimulated a dose-related increase
      (2-fold) in LH receptor mRNA at 2 days (ED50 = 9.0 +/- 1.9 ng/ml) that remained
      constant at 4 days and then declined to basal levels at 6 days. LH stimulated a
      dose-related (ED50 = 17.6 +/- 1.0 pg/ml) increase in LH receptor mRNA that
      reached a maximum of 4-fold at 2 days. At 4 days, LH down-regulated LH receptor
      mRNA below basal levels, and it had no effect at 6 days. Addition of IGF-I (30
      ng/ml) to LH-treated TIC abolished the stimulatory effect of LH throughout the
      culture period. LH receptor mRNA was highly sensitive to LH since the ED50 was
      approximately 2.5-fold lower than for stimulation of androsterone production
      (39.8 +/- 3.8 pg/ml). To understand the molecular mechanism of the synergistic
      stimulation of androgen production by IGF-I and LH, the effects of IGF-I on the
      cAMP/protein kinase A (PKA) signaling pathway were examined. When freshly
      isolated TIC were challenged with IGF-I alone (30 ng/ml), there was no effect on
      cAMP production or PKA activity, but IGF-I augmented LH stimulation of cAMP
      production slightly at high concentrations of LH and blocked stimulation of PKA
      activity by a saturating concentration of LH (3 ng/ml), suggesting that IGF-I
      increased LH down-regulation of PKA. We next examined the effects of IGF-I on LH
      receptor number. When TIC were placed into culture, LH/hCG binding sites
      decreased to approximately 35% of the initial number at 24 h and 25% at 2 days.
      This decrease was accompanied by a similar loss of cholera toxin- and hCG
      stimulated cAMP production.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7529577
TI  - Exquisite sensitivity of electroreceptor in skates.

PMID- 7529578
TI  - A molecular dynamics study of gating in dioxolane-linked gramicidin A channels.
AB  - The gating transition of the RR and SS dioxolane ring-linked gramicidin A
      channels were studied with molecular dynamics simulations using a detailed atomic
      model. It was found that the probable reaction path, describing the transition of
      the ring from the exterior to the interior of the channel where it blocked the
      permeation pathway, involved several steps including the isomerization of the
      transpeptide plane dihedral angle of Val1. Reaction coordinates along this
      pathway were defined, and the transition rates between the stable conformers were
      calculated. It was found, in good accord with experimental observations, that the
      calculated blocking rate for the RR-linked channel was 280/s with a mean blocking
      time of 0.04 ms, whereas such blocking did not occur in the case of the SS-linked
      channel. An important observation is that the resulting lifetime for the blocked
      state of the RR-linked channel was in good accord with the experimental
      observations only when the calculations were performed in the presence of a
      potassium ion inside the channel.

PMID- 7529579
TI  - Estimation of kinetic rate constants from multi-channel recordings by a direct
      fit of the time series.
AB  - The maximum-likelihood technique for the direct estimation of rate constants from
      the measured patch clamp current is extended to the analysis of multi-channel
      recordings, including channels with subconductance levels. The algorithm utilizes
      a simplified approach for the calculation of the matrix exponentials of the
      probability matrix from the rate constants of the Markov model of the involved
      channel(s) by making use of the Kronecker sum and product. The extension to multi
      channel analysis is tested by the application to simulated data. For these tests,
      three different channel models were selected: a two-state model, a three-state
      model with two open states of different conductance, and a three-state model with
      two closed states. For the simulations, time series of these models were
      calculated from the related first-order, finite-state, continuous-time Markov
      processes. Blue background noise was added, and the signals were filtered by a
      digital filter similar to the anti-aliasing low-pass. The tests showed that the
      fit algorithm revealed good estimates of the original rate constants from time
      series of simulated records with up to four independent and identical channels
      even in the case of signal-to-noise ratios being as low as 2. The number of
      channels in a record can be determined from the dependence of the likelihood on
      channel number. For large enough data sets, it takes on a maximum when the
      assumed channel number is equal to the "true" channel number.

PMID- 7529580
TI  - Detection of jumps in single-channel data containing subconductance levels.
AB  - Detection algorithms are widely used for the analysis of single-channel data
      because they remove the background noise from the measured current signal and
      reconstruct the noise-free time series. Standard detection algorithms assume
      channels switching only between zero and full conductance. Many types of
      channels, however, show subconductance levels. A new detection algorithm for data
      containing sublevels, the so-called sublevel Hinkley-detector (SHD), calculates
      several test values in parallel, one for each possible jump. The velocity of
      increase has a maximum for the correct jump. This feature is used to detect the
      jump and to diagnose the new level of current. Because patch-clamp data are
      always filtered by an antialiasing low-pass filter before sampling, the algorithm
      is supplemented by a special diagnosis phase accounting for the distortion of the
      originally rectangular jumps. Along with the reconstructed (noise-free) time
      series the SHD also gives a matrix of the transition counts between the levels.
      This matrix is a useful statistical tool for the decision whether the observed
      channel(s) have in fact a subconductance conformation or if there are simply
      several channels of different conductivity contained within the patch.

PMID- 7529581
TI  - Influence of a channel-forming peptide on energy barriers to ion permeation,
      viewed from a continuum dielectric perspective.
AB  - The continuum three-dielectric model for an aqueous ion channel pore-forming
      peptide-membrane system is extended to account for the finite length of the
      channel. We focus on the electrostatic influence that a channel-forming peptide
      may exert on energy barriers to ion permeation. The nonlinear dielectric behavior
      of channel water caused by dielectric saturation in the presence of an ion is
      explicitly modeled by assigning channel water a mean dielectric constant much
      less than that of bulk water. An exact solution of the continuum problem is
      formulated by approximating the dielectric behavior of bulk water, assigning it a
      dielectric constant of infinity. The validity of this approximation is verified
      by comparison with a Poisson-Boltzmann description of the electrolyte. The formal
      equivalence of high ionic strength and high electrolyte dielectric constant is
      demonstrated. We estimate limits on the reduction of the electrostatic free
      energy caused by ionic interaction with the channel-forming peptide. We find that
      even assigning this region an epsilon of 100, its influence is insufficient to
      lower permeation free energy barriers to values consistent with observed channel
      conductances. We provide estimates of the effective dielectric constant of this
      highly polarizable region, by comparing energy barriers computed using the
      continuum approach with those found from a semi-microscopic analysis of a
      simplified model of a gramicidin-like charge distribution. Possible ways of
      improving both models are discussed.

PMID- 7529582
TI  - The "independence principle" in the processes of water transport.
AB  - The processes of membrane transport exhibiting permeability coefficients
      depending on the species activities do not obey the "independence principle" and
      are assumed to take place by a mechanism of discrete nature, analyzable by a
      kinetic formalism. In this article, we study the dependence of the osmotic
      permeability coefficient on the water activities, from the steady-state analysis
      of a kinetic model of single-file water transport that simultaneously
      incorporates the vacancy-mediated and "knock-on" mechanisms into the state
      diagram. In particular, we study the relation between the near-equilibrium
      osmotic permeability (Pe) and the equilibrium water activity of the compartments
      (w). The analysis and numerical calculations performed for a simple case of the
      model show that, for values of the parameters consistent with experimental data,
      Pe exhibits only a small variation with w within the physiological range in the
      majority of the situations considered here. It is not possible to predict, from
      the study of these simple models, whether more complicated kinetic diagrams of
      water transport may be characterized by permeability coefficients with a more
      evident dependence on the water activities. Nevertheless, the results obtained
      here suggest that, for the case of physiological water pores, the analysis of the
      kinetic dependence of the permeability coefficients on the water activities may
      not yield evidence pointing to a discrete nature for the transport process.

PMID- 7529583
TI  - Absence of effects of low-frequency, low-amplitude magnetic fields on the
      properties of gramicidin A channels.
AB  - The effects of static and low-frequency magnetic fields on gramicidin A channels
      have been investigated using bilayer patch clamp recording and a bridge technique
      capable of detecting 0.3% changes in the conductance of glyceryl monooleate
      membranes containing many channels. In the bridge technique the conductance was
      assessed using 10-ms voltage pulses applied at 10 Hz. Measurements were made for
      LiCl, KCl, and CsCl using magnetic fields of 50, 100, 500, and 5000 microT with
      the frequency scanned from 10-200 Hz. The combinations of static and low
      frequency fields employed include the "cyclotron resonance" conditions at which
      effects had been predicted to occur. In no case was there any detectable change
      in conductance when the magnetic fields were applied or changed. Potassium
      currents through single gramicidin channels have been recorded for patches in
      which several channels may be open at once. Fields were applied for 2 min periods
      interleaved with 2 min controls. Methods have been developed to analyze the
      multichannel records to reveal the amplitude and duration of the channels
      together with the frequency, depth, and apparent period of flickers. No
      significant differences were observed between the control and field-exposed
      recording periods. The peak of the distribution of opening and closing
      transitions always coincided for fields on and off within the resolution, 0.4%,
      of the recordings. There are at least two types of flicker, one with typical
      period less than 0.1 ms, the other with typical period from 0.3-0.8 ms. Most of
      the latter were not complete closures with the conductance during a flicker 15
      20% above the level for a full closure.

PMID- 7529584
TI  - Sodium ion binding in the gramicidin A channel. Solid-state NMR studies of the
      tryptophan residues.
AB  - Gramicidin A analogs, labeled with 13C in the backbone carbonyl groups and the C
      2 indole carbons of the tryptophan-11 and tryptophan-13 residues, were
      synthesized using t-Boc-protected amino acids. The purified analogs were
      incorporated into phosphatidylcholine bilayers at a 1:15 molar ratio and
      macroscopically aligned between glass coverslips. The orientations of the labeled
      groups within the channel were investigated using solid-state NMR and the effect
      of a monovalent ion (Na+) on the orientation of these groups determined. The
      presence of sodium ions did not perturb the 13C spectra of the tryptophan
      carbonyl groups. These results contrast with earlier results in which the Leu-10,
      Leu-12, and Leu-14 carbonyl groups were found to be significantly affected by the
      presence of sodium ions and imply that the tryptophan carbonyl groups are not
      directly involved in ion binding. The channel form of gramicidin A has been
      demonstrated to be the right-handed form of the beta 6.3 helix: consequently, the
      tryptophan carbonyls would be directed away from the entrance to the channel and
      take part in internal hydrogen bonding, so that the presence of cations in the
      channel would have less effect than on the outer leucine residues. Sodium ions
      also had no effect on the C-2 indole resonance of the tryptophan side chains.
      However, a small change was observed in Trp-11 when the ether lipid,
      ditetradecylphosphatidylcholine, was substituted for the ester lipid,
      dimyristoylphosphatidylcholine, indicating some sensitivity of the gramicidin
      side chains to the surrounding lipid.

PMID- 7529587
TI  - Detection of Charcot-Leyden crystals by fluorescence microscopy of Papanicolaou
      stained smears of sputum, bronchoalveolar lavage fluid, and bronchial secretions.
AB  - Fluorescence microscopy was used to examine Papanicolaou-stained smears of sputum
      and other secretions from the respiratory tract. Under these conditions Charcot
      Leyden crystals (CLC) appear as bright yellow-green fluorescing needles. The
      study was performed to determine the value of this approach for the diagnosis of
      allergic lung diseases. The time taken to detect the crystals was recorded and
      the sensitivity of fluorescence microscopy for the detection of CLC was compared
      with light microscopy of the same samples. The data show that fluorescence
      microscopy is superior to light microscopy for the detection of CLC. The
      characteristic needle-shaped crystal can be recognized easily and fragments of
      crystals could be easily identified. In doubtful cases of allergic lung diseases,
      fluorescence microscopy may be used to supplement light microscopy for the
      detection of Charcot-Leyden crystals.

PMID- 7529588
TI  - Scrape cytology in the diagnosis of Paget's disease of the breast.
AB  - Eczema of the nipple is an important symptom presenting to the general surgeon in
      the out-patient department. The diagnosis of Paget's disease of the nipple has
      traditionally been made by incision biopsy necessitating at least a local
      anaesthetic. We present 14 patients with nipple skin change, in whom the
      technique of scrape cytology was used to identify patients with Paget's disease.
      In our series eight cases of Paget's disease were successfully identified by
      scrape cytology with no false negatives or positives. We suggest that this is a
      quick, easy, non-invasive method of screening eczema of the nipple in the out
      patient clinic.

PMID- 7529586
TI  - Interaction of apical and basal membrane ion channels underlies electroreception
      in ampullary epithelia of skates.
AB  - The exquisite sensitivity of elasmobranch fishes to electric fields is thought to
      reside in electroreceptive organs called ampullae of Lorenzini. We measured the
      stimulus-response behavior of ampullary organs excised from skates. Under open
      circuit conditions, the ampullary organ showed three distinct response states:
      spontaneous repetitive spikes, evoked spikes, and small, damped oscillatory
      responses. Under short-circuit conditions, the amplitude range for a linear
      current response to a sinusoidal (0.5 Hz) voltage clamp of an organ (assessed by
      spectral analysis of the harmonics generated) was 7-200 microV rms. Changes in
      the spike firing rate of the afferent nerve innervating the organ were evident
      for voltage clamps of the ampullary epithelium of 3 microV and the spike rate
      saturated for clamp steps exceeding 100 microV. Thus, the linear response range
      of the ampullary epithelium exceeded the range in spike firing rate of the
      afferent nerve. The steady-state transorgan electrical properties under voltage
      clamp conditions were obtained by analysis of complex admittance determinations
      in the frequency range 0.05-20 Hz for perturbations (< 100 microV rms) in the
      linear range. Admittance functions were distinctly related to the preparation
      states observed under open-circuit conditions. A negative real part in the organ
      admittance (i.e., a steady-state negative conductance generated by the
      preparation) was a common characteristic of the two (open-circuit) excitable
      states. The negative conductance was also confirmed by the direction of current
      flow through the ampullary epithelium in response to step voltage clamps. We
      conclude that the steady state-negative conductance is an essential property of
      the ampullary epithelium,and we suggest that the interplay of negative and
      positive conductances generated by ion channels in apical and basal membranes of
      receptor cells results in signal amplification that may contribute significantly
      to the electric field sensitivity of ampullary organs.

PMID- 7529585
TI  - Parallel helix bundles and ion channels: molecular modeling via simulated
      annealing and restrained molecular dynamics.
AB  - A parallel bundle of transmembrane (TM) alpha-helices surrounding a central pore
      is present in several classes of ion channel, including the nicotinic
      acetylcholine receptor (nAChR). We have modeled bundles of hydrophobic and of
      amphipathic helices using simulated annealing via restrained molecular dynamics.
      Bundles of Ala20 helices, with N = 4, 5, or 6 helices/bundle were generated. For
      all three N values the helices formed left-handed coiled coils, with pitches
      ranging from 160 A (N = 4) to 240 A (N = 6). Pore radius profiles revealed
      constrictions at residues 3, 6, 10, 13, and 17. A left-handed coiled coil and a
      similar pattern of pore constrictions were observed for N = 5 bundles of Leu20.
      In contrast, N = 5 bundles of Ile20 formed right-handed coiled coils, reflecting
      loosened packing of helices containing beta-branched side chains. Bundles formed
      by each of two classes of amphipathic helices were examined: (a) M2a, M2b, and
      M2c derived from sequences of M2 helices of nAChR; and (b) (LSSLLSL)3, a
      synthetic channel-forming peptide. Both classes of amphipathic helix formed left
      handed coiled coils. For (LSSLLSL)3 the pitch of the coil increased as N
      increased from 4 to 6. The M2c N = 5 helix bundle is discussed in the context of
      possible models of the pore domain of nAChR.

PMID- 7529589
TI  - NBQX suppresses inhibitory glycine currents in retinal ganglion cells.
AB  - The quinoxaline NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) quinoxaline) is
      a potent non-NMDA receptor antagonist, which appears to be relatively free of
      antagonistic action at the glycine binding site of the NMDA receptor. However, we
      report here that at 50 microM, NBQX significantly attenuated the inhibitory
      currents induced by the exogenous application of 100 microM glycine as observed
      using whole-cell recordings from ganglion cells in a slice preparation of the
      tiger salamander retina. In contrast, NBQX had no effect on GABA-mediated
      inhibition. This observation suggests that care should be taken when attributing
      the action of NBQX solely to its antagonism of non-NMDA glutamate receptors,
      particularly when higher concentrations are used.

PMID- 7529591
TI  - NADPH diaphorase neurones are evenly distributed throughout cat neocortex
      irrespective of functional specialization of each region.
AB  - Using NADPH diaphorase histochemistry as a marker for nitric oxide synthase we
      investigated the possible sites of nitric oxide synthesis in cat cerebral
      neocortex. Intensely stained neurones were found mainly in the deep layers of the
      neocortex and underlying medulla. Virtually all neurones in the cerebral medulla
      were NADPH diaphorase positive. The density of diaphorase neurones was estimated
      in the cortex/medulla border zones of each neocortical gyrus. Diaphorase neurones
      were evenly distributed throughout the neocortex and no significant statistical
      difference between gyri was observed. These findings indicate that the density of
      diaphorase neurones is irrespective of functional specialization of each region
      and are more in line with the hypothesis that NADPH diaphorase neurones are
      involved in the control of local cortical blood flow.

PMID- 7529590
TI  - Down regulation of nestin by TGF-beta or serum in SFME cells accompanies
      differentiation into astrocytes.
AB  - The serum-free mouse embryo (SFME) cell line, derived from 16-day-old mouse
      embryos in medium in which serum was replaced by growth factors and other
      supplements, has been cultured for more than 200 generations. SFME cells are
      nontumorigenic, lack gross chromosomal abnormalities, and display characteristics
      of CNS progenitor cells. SFME cells show reversible induction of the astrocyte
      specific marker glial fibrillary acidic protein when cultured in the presence of
      TGF-beta or serum. In order to determine if SFME cells exhibit further
      characteristics of CNS progenitor cells we investigated the expression of the
      gene encoding nestin, an intermediate filament protein expressed by
      neuroepithelial stem cells of the CNS. SFME cells express nestin in serum-free
      medium, and nestin expression is reversibly down-regulated by TGF-beta or serum.
      These results demonstrate that nestin expression is regulated by factors present
      in serum and support the hypothesis that SFME cells represent a CNS progenitor
      cell.

PMID- 7529592
TI  - Differential RNA editing efficiency of AMPA receptor subunit GluR-2 in human
      brain.
AB  - RNA editing in rat brain has been found to control a determinant of cation flow
      in alpha-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid (AMPA)-gated
      channels. Here we provide the first evidence that this RNA editing phenomenon
      occurs in human brain and is differentially regulated. Sequence analysis of human
      genomic DNA revealed a Q codon (CAG) in the putative channel-forming segment of
      human GluR-2, whereas in the majority of cDNA clones an R codon (CGG) was found.
      Examination of editing in various brain tissues revealed differences in the
      efficiency of this process. The hippocampus, cerebellum and temporal cortex
      harbour 100% edited GluR-2, whereas only 72% of substantia nigra, 89% of corpus
      striatum and 96% of fetal cDNAs have been found to be edited. This new discovery
      of differential efficiency of RNA editing has important implications in AMPA
      receptor channel-mediated calcium influx. AMPA receptors are thought to mediate
      the majority of the fast excitatory synaptic neurotransmission; the RNA editing
      process may therefore play a critical role in normal brain function and
      development. Dysfunction of this RNA editing process may have neuropathological
      consequences and could be related to certain neurodegenerative diseases.

PMID- 7529595
TI  - [Immunochemical analysis of common antigenic determinants in insulin and
      apoprotein B].

PMID- 7529594
TI  - [Change in the tone of coronary vessels as a result of immobilization stress].

PMID- 7529593
TI  - Cystic fibrosis transmembrane conductance regulator protein expression in brain.
AB  - The cystic fibrosis transmembrane conductance regulator protein (CFTR) has been
      identified in bovine brain clathrin-coated vesicles, rat brain and a human
      neuroblastoma cell line using affinity-purified polyclonal peptide antibodies
      against CFTR. Immunocytochemical staining of multiple dendrites and soma of
      neurons of the diencephalon, midbrain, pons and medulla oblongata, has also been
      demonstrated. Whole cell lysates and membranes derived from rat brain,
      neuroblastoma cells and bovine brain clathrin-coated vesicles express the mature
      150-165 kDa and 130 kDa unglycosylated forms of CFTR. The localization of CFTR to
      brain regions controlling homeostasis and energy expenditure may relate to the
      pathogenesis of non-pulmonary manifestations of cystic fibrosis. CFTR expression
      in neurons and coated vesicles suggests a possible effect on neuropeptide vesicle
      trafficking by mutant CFTR.

PMID- 7529596
TI  - [Expression of various keratins in basal cell, metastatic, and squamous cell skin
      cancer].

PMID- 7529597
TI  - [The effect of plasmin and its complexes with alpha 2-macroglobulin and alpha 2
      antiplasmin on the proliferative activity of human lymphocytes].

PMID- 7529600
TI  - The psychological development of children of epileptic parents. I. Study design
      and comparative findings.
AB  - We studied the genetic, neurobiological, teratogenic and psychosocial risks for
      the development of children born to epileptic parents in (a) children of
      epileptic mothers with intrauterine exposure to anticonvulsants, (b) children of
      epileptic mothers without intrauterine exposure to anticonvulsants and (c)
      children of epileptic fathers. In addition, three matched control groups were
      also considered. The longitudinal design of the study covered newborns to
      children of six years of age. A wide range of developmental and psychological
      tests and a structured interview for the assessment of psychiatric symptoms were
      used. It was shown that teratogenic factors are operant, whereas there was no
      indication that the condition of epilepsy in the parents per se had any effect on
      the developmental outcome of the children. The possible teratogenic effect of
      anticonvulsants should be studied in more detail.

PMID- 7529599
TI  - Regulation of vitronectin receptor expression by retinoic acid on human melanoma
      cells.
AB  - The integrin family of adhesion receptors is likely to be important for tumor
      cell invasion and dissemination. We have studied the effects of the
      differentiating agents retinoic acid on integrin expression by the human melanoma
      cell line MeWo. Our results show that this agent inhibits cellular proliferation,
      increases melanin content and induces morphological changes in MeWo cells.
      Functionally, these alterations are associated with an enhanced adhesion to
      matrix protein vitronectin and higher levels of expression of vitronectin
      receptor on the cell surface. This is accompanied by increased levels of alpha v
      integrin mRNA. Although the mechanism by which retinoic acid regulates the
      expression of vitronectin receptor in MeWo cells needs further examination, this
      system may represent a good model for understanding the role of this receptor in
      melanoma progression, as well the molecular basis for retinoic acid therapy in
      these tumors.

PMID- 7529601
TI  - The psychological development of children of epileptic parents. II. The
      differential impact of intrauterine exposure to anticonvulsant drugs and further
      influential factors.
AB  - After obtaining evidence that tetratogenic effects were operant in a sample of
      children born to epileptic mothers, we analyzed the effects of type of medication
      and further influential factors. Children with prenatal exposure to polytherapy
      had significantly lower scores than controls for a large number of psychological
      tests. In addition to polytherapy, there were even stronger effects of
      socioeconomic status and sex was found to be less influential than polytherapy.
      Among further epilepsy variables, only seizure frequency of the mother during
      pregnancy had a modest impact on the child's developmental outcome, whereas a
      score of obstetric abnormality was less effective in predicting developmental
      outcome, as measured and defined by various standardized psychological tests.

PMID- 7529602
TI  - Reliability of polymerase chain reaction (PCR) analysis of single cells for
      preimplantation genetic diagnosis.
AB  - PURPOSE: We investigated the reliability of polymerase chain reaction (PCR)
      genotype analyses performed on single cells for the purposes of preimplantation
      genetic analysis. METHODS: We performed blind analysis of 130 single skin
      fibroblasts heterozygous for the delta-F508 mutation in the cystic fibrosis
      transmembrane regulator (CFTR) gene and 73 single skin fibroblasts from an
      individual heterozygous for the XbaI polymorphic site of the Factor VIII gene.
      RESULTS: Amplification was successful for 116 cells and 52 cells respectively and
      in all but one case (a CFTR analysis) both alleles were amplified. The incidence
      of diagnostic error was 1 out of 203 analyses or 0.0043. We conclude that PCR is
      a reliable method for determining the genotype of single cells for the purposes
      of preimplantation genetic analysis.

PMID- 7529598
TI  - The insulin-like growth factor system as a target in breast cancer.
AB  - Evidence from several experimental systems has shown that the insulin-like growth
      factors (IGFs) can stimulate breast cancer proliferation. Since IGF action is
      mediated by interaction with specific cell surface receptors, interruption of
      these signalling pathways could result in inhibition of cellular growth. In all
      extracellular fluids, the IGFs are associated with high affinity binding
      proteins, the IGFBPs can bind the IGFs and prevent receptor activation, and thus
      might have a role in a targeted approach to breast cancer therapy. Here we
      present our studies using IGFBP-1 to inhibit growth of the breast cancer cell
      line MCF-7.

PMID- 7529604
TI  - Demonstration of carbohydrate-specific immunoglobulin G4 antibodies in sera of
      patients receiving grass pollen immunotherapy.
AB  - From a group of 92 patients receiving grass pollen immunotherapy, and selected on
      grounds of high IgG4 titers against Lol p I, sera were tested for IgG4 antibodies
      against the glycosylated grass pollen allergen Lol p XI. In 72 of 92 cases IgG4
      antibodies were demonstrated. The N-glycan of Lol p XI was earlier shown to be an
      epitope for IgE antibodies. In the present study it was demonstrated that the
      carbohydrate structure is also recognized by IgG4 antibodies, illustrating that
      IgG4 responses are not immuno-restricted to peptide epitopes, as was suggested in
      several reports.

PMID- 7529603
TI  - Ectopic pregnancies after in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: Our objective was to analyze the risk factors, stimulation
      characteristics, and future fecundity of patients with ectopic pregnancies after
      in vitro fertilization (IVF). METHODS: We retrospectively evaluated all cases of
      ectopic pregnancy occurring between January 1989 and March 1993 (Cornell series 1
      to 17). A case-control group of intrauterine pregnancies was used for comparison
      of the stimulation and transfer characteristics. RESULTS: Twenty-seven of 1123
      pregnancies (2.4%) were ectopic, following 2812 fresh IVF embryo transfers, while
      8 of 105 pregnancies (7.6%) were ectopic, following 405 frozen-thawed embryo
      transfers. Tubal factor was the cause of infertility in the majority (85.7%) of
      ectopic pregnancies. No difference was found between the ectopics and the matched
      controls in stimulation and transfer characteristics. Thirty ectopic pregnancies
      were ampullary, two were interstitial, two were cervical, and one was
      heterotopic. Twenty of the patients subsequently underwent 29 IVF attempts, with
      a pregnancy rate of 41.4% per transfer. CONCLUSIONS: Ectopic pregnancy after IVF
      appears to be related to preexisting tubal pathology; embryo transfer of
      cryopreserved thawed embryos in a natural cycle may result in a higher ectopic
      rate in these patients; in subsequent IVF cycles the intrauterine pregnancy rate
      of these patients is not decreased.

PMID- 7529605
TI  - The management of chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) is a major cause of late morbidity and
      mortality following allogeneic marrow transplantation. The pathogenesis and
      clinical features of chronic GVHD resemble those of several autoimmune diseases
      including progressive systemic sclerosis, systemic lupus erythematous, lichen
      planus, Sjogren's syndrome, rheumatoid arthritis, and primary biliary cirrhosis.
      Chronic GVHD retards the tempo of immune reconstitution following allogeneic
      transplantation and is a major risk factor for late infections. Although in vivo
      immunosuppression and in vitro depletion of T-cells can reduce the incidence of
      acute GVHD, improved long-term survival free of chronic GVHD has not been
      observed. Early treatment of multiorgan extensive chronic GVHD with an
      alternating-day regimen of cyclosporine and prednisone has led to improved
      disability-free survival. Functional performance of the long-term survivors
      receiving combination immunosuppressive therapy remained near normal and the
      incidence of disabling scleroderma has decreased from over 50% to 6%. However,
      infections remain a frequent cause of morbidity especially in high-risk patients
      with advanced age, HLA-nonidentical marrow grafts, progressive onset of chronic
      GVHD and continued thrombocytopenia.

PMID- 7529606
TI  - Clinical use of hematopoietic growth factors in allogeneic bone marrow
      transplantation.
AB  - The use of the recombinant hematopoietic growth factors G-CSF and GM-CSF have
      shortened the period of neutropenia, or avoided this problem, in many cancer
      patients who have received cytotoxic therapy. Although these benefits have been
      particularly striking in the autologous bone marrow and/or autologous peripheral
      blood progenitor cell transplant setting, most data suggest that the use of G-CSF
      and GM-CSF only marginally enhance recovery of the neutrophil count when
      administered after allogeneic bone marrow infusion. Furthermore, in the allograft
      setting these expensive agents have not provided benefit in the form of enhanced
      platelet count recovery, lessening the incidence of graft-versus-host disease, or
      improvement in overall survival. These data do not justify routine widespread use
      of G-CSF and GM-CSF and suggest that these agents should be reserved for patients
      who experience delay in engraftment after allogeneic bone marrow infusion.
      Administration of erythropoietin, on the other hand, may reduce the need for
      homologous red blood cell transfusions, and may increase the safety margin for
      both the allogeneic bone marrow recipient and as well as the donor. Recombinant
      hematopoietic growth factors targetted specifically to enhance platelet recovery
      after transplantation (such as interleukin-3, interleukin-6, and interleukin-11)
      have shown promise after autotransplantation and after conventional dose
      chemotherapy, and likely will be evaluated in the allogeneic transplant patient.

PMID- 7529607
TI  - Care of dying patients in hospital. Why care of the dying is still poor.

PMID- 7529609
TI  - Assessment of complete remission after 2-chlorodeoxyadenosine for hairy cell
      leukemia: utility of marrow immunostaining and measurement of splenic index.
AB  - 2-Chlorodeoxyadenosine (2-CdA) yields high complete remission (CR) rates in
      patients with hairy cell leukemia (HCL) Two approaches were used to detect
      minimal residual disease. We studied two B-lineage antibodies, L26 and MB2, and a
      T-lineage antibody, UCHL-1, in fixed marrow core biopsies from 34 patients with
      HCL before and after 2-CdA to detect minimal residual in the marrow. In addition,
      the splenic index was calculated before and after treatment to detect residual
      splenomegaly. Prior to therapy, hairy cells exhibited intense cytoplasmic
      membrane reactivity with L26 and strong intracytoplasmic reactivity with MB2.
      UCHL-1 did not react with hairy cells. Thirty-one patients were assessable 3
      months after therapy. Five of 24 (21%) patients in CR by routine evaluation had
      residual HCL detected by immunostaining. Four of these 5 patients have been
      reevaluated at 1 year. One patient relapsed by routine evaluation, 2 remained
      positive by immunostaining alone, and 1 patient became negative by
      immunostaining. A total of 19 patients have been evaluated at 1 year and 17
      remain in CR. Three of these 17 were positive by immunostaining, 2 of whom had
      been positive at 3 months and 1 additional patient who became positive by
      immunostaining at 1 year. Of 9 patients evaluated at 2 years, an additional 2 of
      3 patients with minimal residual disease detected previously by immunostaining at
      3 months relapsed by routine morphology and 1 had persistent positive
      immunostaining. Only 1 patient in remission by morphology and immunostaining has
      relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529608
TI  - Dying for palliative care.

PMID- 7529612
TI  - [Ultrastructure of muscle spindles in an autotransplant of the rat skeletal
      muscle (M. extensor digitorum longus)].

PMID- 7529610
TI  - Changes in gene expression of AMPA-selective glutamate receptor subunits induced
      by status epilepticus in rat brain.
AB  - In the present investigation we address the question of whether one of the
      responses to increased neuronal activity is a modification of the expression of
      the different subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA)-selective glutamate receptors (GluR-1, GluR-2, GluR-3). Thus, we used two
      different models of generalized status epilepticus, as widespread elevated
      neuronal activity, to study in vivo responses of the AMPA receptor mRNA
      expression in rat forebrain. By Northern blot analysis and in situ hybridization,
      we show that one of the delayed responses to LiCl/pilocarpine-induced status
      epilepticus is a dramatic change in the mRNA level of some subunits of AMPA
      selective glutamate receptors. These effects, which appear between 6 and 12 h
      after the drug treatment, are subunit and brain region specific. The most
      striking example of differential expression of the three examined GluR mRNAs can
      be observed in the dentate gyrus of the hippocampus. In this specific brain
      subregion an increase of GluR-3 mRNA level is induced 12 h after LiCl/pilocarpine
      treatment, while a clear decrease in GluR-1 mRNA level and no significant change
      in GluR-2 mRNA level can be observed in the same area under these experimental
      conditions. Both the GluR-1 decrease and the GluR-3 increase are transient
      effects and a return to basal level can be observed after 48-72 h. In the CA1
      layer of the hippocampus, a parallel decrease of both GluR-1 and GluR-3
      expression is found 12-24 h after drug treatment, followed by a recovery of the
      expression to control values at 48 h. In kainate-induced epilepsy we could
      reproduce the late increase (12-24 h) in GluR-3 mRNA in the dentate gyrus;
      however, under this experimental condition, no clear decrease of GluR-1
      expression can be observed in this area. A general decrease in mRNA level for the
      AMPA receptor subunits (GluR-1-3) in the hippocampal layers, in particular in CA3
      and CA4 subfields, was also observed. In conclusion the results reported in the
      present paper reveal a specific regulation of GluR gene expression in the granule
      cells of the hippocampal dentate gyrus and stimulate further investigation on the
      functional role of the GluR-3 subunit in the receptor-channel complex.

PMID- 7529611
TI  - Excitotoxicity of glutamate and four analogs in primary spinal cord cell
      cultures.
AB  - Continuous glutamate exposure produced widespread neuronal damage in mixed whole
      dissociated murine spinal cord cell cultures. Ethidium bromide and acridine
      orange staining revealed that a 24 h glutamate exposure produced nearly 98%
      neuronal cell death but the underlying glia were spared. Continuous exposure to
      glutamate, N-methyl-D-aspartate (NMDA), kainate and quisqualate produced time
      dependent and dose-dependent cell death as measured by the assay of lactate
      dehydrogenase activity in the cell culture media. Glutamate (500 microM), NMDA
      (100 microM) and kainate (500 microM) were equally neurotoxic. In contrast,
      quisqualate (100 microM) was only partially neurotoxic compared to the other
      glutamate analogs. The neurotoxicity of glutamate was blocked by the NMDA
      antagonist, MK-801. The neurotoxicity of kainate and quisqualate was blocked with
      the non-NMDA antagonist CNQX. Continuous exposure to (1S,3R)-1-aminocyclopentane
      1,3-dicarboxylic acid (1S,3R-ACPD) was not neurotoxic, even at concentrations up
      to 1 mM.

PMID- 7529613
TI  - Suppressive effects of the anti-allergic drugs, tranilast and azelastine, on the
      lysophosphatidylserine-dependent activation of rat mast cells.
AB  - Anti-allergic drugs, tranilast and azelastine, were examined for their effects on
      lysophosphatidylserine (lysoPS)-dependent histamine release from rat mast cells.
      Although both compounds suppressed the histamine release in a dose-dependent
      manner, the inhibition was affected by lysoPS concentration differently. In the
      presence of an increasing concentration of lysoPS, the suppressive effect of
      tranilast decreased. The inhibition by azelastine, however, was independent of
      the concentration of lysoPS. The findings suggest that these two drugs inhibit
      lysoPS-depedent histamine release through essentially different routes.

PMID- 7529614
TI  - Proteolytic enzymes and amylase induce cytokine production in human peripheral
      blood mononuclear cells in vitro.
AB  - In vitro treatment of human peripheral blood mononuclear cells (PBMNC) with
      proteolytic enzymes (bromelain, papain) and amylase leads to the production of
      large amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL
      1 beta), and interleukin-6 (IL-6) in a time and dose dependent manner. Increased
      TNF-alpha and IL-6 production was already found after 4-6 hours of incubation,
      and plateau levels were reached after 12-16 hours. Plateau levels up to 1500 pg
      TNF-alpha/ml/10(6) PBMNC, 13000 pg IL-1 beta/ml/10(6) PBMNC, and 23000 pg IL
      6/ml/10(6) PBMNC were observed. Control cultures contained below 35 pg/ml/10(6)
      PBMNC of TNF-alpha, IL-1 beta or IL-6. In contrast to TNF-alpha which was
      undetectable after more than 24 hours, peak levels of IL-1 beta and IL-6 were
      still present at 24 hours. After incubation of the enzyme solution for some hours
      at 56 degrees C the cytokine inducing capacity disappeared. Neutralization
      experiments with inactivating antibodies, radioimmunoassay, and western blotting
      after electrophoretic separation showed that the TNF-like activity found in the
      lytic assay was due to TNF-alpha. Interferon-alpha (IFN-alpha) and Interferon
      gamma (IFN-gamma), which had no effect alone, synergistically increased TNF-alpha
      production when applied together with the enzymes. A commercial mixture of these
      enzymes (Wobenzym), which was also investigated, showed a similar concentration
      and time dependence, as well as synergism with the interferons. A synergistic
      effect on TNF-alpha production was also found with the enzymes and phorbol ester
      (PMA).

PMID- 7529615
TI  - Pediatric defecation in 1994 America.

PMID- 7529616
TI  - A stochastic model for the evolution of autocorrelated DNA sequences.
AB  - Currently used stochastic models of DNA sequence evolution assume independent and
      identically distributed nucleotide sites. They are too simple to account for
      dependence structures obviously present in molecular data. Up to now more
      realistic stochastic models for nucleotide substitutions have been considered
      intractable. In this paper a procedure that accounts for non-overlapping
      correlations among pairs of sites of a DNA sequence is developed. We show that
      currently used models that ignore correlated sites underestimate distances
      inferred from observed sequence dissimilarities. For the analyzed mitochondrial
      sequence data this underestimation is not drastic in contrast to paired regions
      (stems) of bacterial 23S rRNA sequences.

PMID- 7529617
TI  - Tenascin expression in inflammatory, dysplastic and neoplastic lesions of the
      human stomach.
AB  - We studied the expression of tenascin (Tn) in human stomach. In the normal mucosa
      of the antrum and body, Tn reaction was only seen in the muscularis mucosae, in
      the region of the pyloric sphincter and in the duodenum, a Tn-immunoreactive rim
      was seen underlying surface epithelial cells. Antral gastritis, irrespective of
      the degree of inflammation, showed a rim-like Tn expression under the surface
      epithelial cells but no Tn reaction was seen in mild chronic gastritis of the
      body. In some moderate and severe examples of chronic gastritis a delicate Tn
      reactive line was seen to underline the surface epithelium focally and the neck
      regions of gastric pits. Discontinuous Tn immunoreactivity was sometimes seen
      beneath hyperplastic epithelium in both parts of the stomach. A Tn-immunoreactive
      line was seldom seen surrounding glands showing intestinal metaplasia. In both
      benign and malignant ulcers prominent Tn immunoreaction was seen at the base of
      ulcers extending deep into the underlying muscularis. Only severely dysplastic
      lesions displayed Tn in the lamina propria, in close association with
      capillaries. In early forms of diffuse gastric cancer (DGCA) raggedly increased
      Tn staining was seen in the lamina propria underlying affected surface epithelial
      cells. In advanced forms of DGCA consistent Tn expression was seen in the tumour
      stroma. A distinct Tn reaction was seen surrounding invasive tumour cell nests of
      intestinal type gastric cancer (IGCA) in the submucosa, whereas in early forms of
      the tumour enhanced Tn reaction was noted predominantly in the upper part of the
      lamina propria in the vicinity of dysplastic elements. Notably, while most
      invading DGCA tumour cell nests showed no Tn in the submucosa and muscle cell
      layer, invading IGCA islets showed prominent expression of Tn. The most
      conspicuous Tn enhancement in the stomach is seen in invasive tumours and in
      ulcers suggesting that Tn is an important stromal component in malignant growth
      and in lesions undergoing active repair and remodelling.

PMID- 7529619
TI  - Cell culture from rat renal glomeruli.
AB  - The primary culture of rat renal glomeruli was found to result in the ready
      outgrowth of two cells types. One type designated c-cells were cytokeratin
      positive and exhibited microvilli and cilia. The second type designated f-cells
      were vimentin positive and showed rugose surfaces. C-cells were polygonal in
      culture on plastic surfaces and were derived from cells of parietal epithelial
      origin. F-cells assumed a more extended form on plastic and were judged to be a
      sub-set of parietal epithelial cells. Neither cell type was derived from the
      visceral epithelium which was found to have been destroyed during isolation of
      the glomeruli. When cultured on isolated glomerular basement membrane both the c
      cells and f-cells assumed a polygonal morphology but when grown on Matrigel the
      cells assumed the form of long strands interconnecting the outgrowths between the
      glomeruli. The appearance of the cells in the strands, judged from scanning
      electron microscopy, suggested that these were formed from f-cells but other cell
      types were entrained in the structures. Glomeruli subjected to vigorous
      proteinase digestion of the basement membrane allowed culture of a wider variety
      of cells. These included endothelial cells, judged by OX-43 antibody and anti-von
      Willebrand Factor staining, and mesangial cells. In cultures from glomeruli
      polygonal cells are often assumed to be visceral epithelial cells, the results
      from this study indicate that this assumption is unsound. The very different
      behaviour of cells grown on isolated basement membrane as compared with cells
      grown on Matrigel suggests that Matrigel may not faithfully mimic basement
      membrane with respect to cell response in culture.

PMID- 7529618
TI  - In situ expression of beta 1, beta 3 and beta 4 integrin subunits in non
      neoplastic endothelium and vascular tumours.
AB  - Endothelial cells play an important role in adhesive interactions between
      circulating cells and extracellular matrix proteins. In vitro studies have shown
      that many of these processes are mediated by a superfamily of alpha beta
      heterodimeric transmembrane glycoproteins called integrins. The distribution
      patterns of beta 1, beta 3 and beta 4 integrin subunits in endothelial cells (EC)
      in situ were examined immunohistochemically on serial frozen sections of a wide
      range of non-neoplastic tissues and of vascular tumours, both benign and
      malignant. Expression of the beta 1 subunit was a constitutive feature of EC.
      Among the beta 1-associated alpha subunits, alpha 5 and alpha 6 were broadly
      distributed in EC, irrespective of vessel size and microenvironment. The alpha 3
      subunit displayed intermediate levels of expression with a slight preference for
      small vessel EC. Presence of alpha 1 was confined to EC of capillaries and
      venules/small veins. Expression of alpha 2 in EC was inconsistent. With rare
      exceptions, the alpha 4 chain was absent in EC. The beta 3 and alpha v subunits
      were expressed in most EC, though not always concomitantly. In contrast to the
      beta 1 chain, however, these integrin subunits were absent in EC of glomerular
      capillaries and were expressed variably in sinusoidal EC. The beta 4 chain was
      evenly present in the great majority of EC, except for those of large vessels. In
      vascular tumours, the patterns of beta 1 and alpha 1 to alpha 6 subunit
      expression generally corresponded to those found in their non-neoplastic
      counterparts. Expression of beta 3, alpha v and beta 4 chains, however, decreased
      in neoplasia, especially in angiosarcomas. These data show that EC dispose of
      broad and at the same time differential repertoires of integrin subunits that
      presumably reflect vessel-type associated functional differences among these
      cells. In vascular tumours, the orthologous distribution patterns of beta 1 and
      alpha 1 to alpha 6 chains are conserved in most instances while the amounts of
      beta 3, alpha v and beta 4 subunits expressed in EC tend to decrease in the
      course of malignant transformation.

PMID- 7529624
TI  - Inexpensive computer analysis of cell and tissue stainings.

PMID- 7529621
TI  - Synchronous appearance of fibronectin, integrin alpha 5 beta 1, vinculin and
      actin in epithelial cells and fibroblasts during rat tracheal wound healing.
AB  - The distribution of integrin alpha 5 beta 1 (alpha 5 beta 1) and associated
      components during wound healing was investigated in the rat trachea following
      mechanical injury. Under anesthesia, the ventral surface of the trachea was
      scratched, and tissue specimens were obtained from 6 h to 3 weeks after injury
      and studied using light and electron microscopy and immunohistochemistry. alpha 5
      beta 1, vinculin and actin in regenerating epithelial cells and extracellular
      fibronectin appear virtually simultaneously after injury (from 12 h to 7 days) as
      do alpha 5 beta 1, vinculin and alpha-smooth muscle actin in fibroblasts and
      cellular fibronectin in granulation tissue (from 3 to 10 days). Immunoelectron
      microscopy 2 days after injury showed that alpha 5 beta 1 and vinculin were
      localized on the basal and lateral surfaces of regenerating epithelial cells and
      fibroblast surfaces, and fibronectin was localized just under the regenerating
      epithelial cells, around collagen fibrils and sporadically around fibroblasts.
      Bromodeoxyuridine labeling showed that the appearance of these components was
      associated with the period of cell proliferation. The appearances of fibronectin,
      alpha 5 beta 1, vinculin and actin in regenerating epithelial cells and
      fibroblasts during tracheal wound healing are well coordinated. During the
      initial cell migration phase, plasma fibronectin may stimulate cell migration
      before cellular fibronectin is produced in situ, and regenerating epithelial
      cells appear to begin to migrate into the wound before cell proliferation starts.

PMID- 7529625
TI  - Cytotoxic effects of FK506 on human renal proximal tubule cells in culture.
AB  - FK506 has been used as the primary immunosuppressive agent administered after a
      variety of organ transplants, with less reported nephrotoxicity than that of
      cyclosporine. This study examined in vitro cytotoxicity of FK506 on normal human
      renal proximal tubule cells. Cytotoxicity was assessed by neutral red inclusion
      and trypan blue exclusion; morphology was assessed by light and transmission
      electron microscopy. Neutral red inclusion decreased to less than 10% of the
      control after 3 days exposure to 200 micrograms/ml FK506. Forty microgram per
      milliliter FK506 caused a decrease in neutral red inclusion to 61% of the control
      on Day 7, with recovery to 86% on Day 12. Similarly, trypan blue exclusion
      decreased to 66% of the control following 7 days exposure to 40 micrograms/ml
      FK506, and confluency of the monolayer was reduced to 50% as evidenced by phase
      contrast microscopy. After a 12-day exposure, treated monolayers became more
      confluent. On ultrastructural examination, FK506-treated cells exhibited
      increased cytoplasmic vacuolation and lipid inclusion. These data suggest that
      FK506 is reversibly and mildly toxic to monolayers of human renal proximal tubule
      cells and are consistent with clinical reports of reversible nephrotoxicity.

PMID- 7529622
TI  - Hyperplasia of epithelium adjacent to transitional cell carcinoma can be induced
      by growth factors through paracrine pathways.
AB  - Hyperplasia of transitional cell epithelium adjacent to human transitional cell
      carcinomas (TCC) is a common finding in pathology. This hyperplasia may be a
      precancerous aberration. Alternatively, it has been suggested that the
      hyperplasia is due to paracrine action of tumour-derived growth factors. In this
      study we tested the latter hypothesis using the mouse tumorigenic TCC cell line
      NUC-1. Transplantation of NUC-1 tumour cells into the urinary bladder submucosa
      of syngeneic mice in vivo induced hyperplasia of normal adjacent urothelium in
      all tested mice. Implantation of normal mouse bladder mucosa did not induce
      urothelial hyperplasia. In vitro, conditioned medium of NUC-1 cells induced the
      proliferation of the mouse urothelial cell line g/G, which closely resembles
      normal urothelial cells. This induction was inhibited by transforming growth
      factor beta 1 (TGF beta 1). Similarly, TGF beta 1 inhibited the fibroblast growth
      factor-1 (FGF-1) and FGF-2 induced proliferation of g/G cells. Chemico-physical
      examination, bioassays with conditioned media, and RNA analysis of NUC-1 cells
      revealed that these cells secreted a growth factor with FGF-like properties.
      These results indicate that epithelial hyperplasia surrounding carcinomas is not
      necessarily a precancerous aberration, but may result from direct paracrine
      action of tumour-derived growth factors.

PMID- 7529623
TI  - Vaginal clear cell carcinoma in a young patient with ectopic termination of the
      left ureter in the vagina.
AB  - The association of clear cell adenocarcinoma of the vagina and vaginal adenosis
      with prenatal exposure to diethylstilbestrol (DES) is well-documented in the
      United States. In Europe, however, DES was never used in the therapy of
      threatened abortion and, therefore, clear cell adenocarcinoma and vaginal
      adenosis remained rare diseases. We report on the clinical and pathological
      features of a case of clear cell adenocarcinoma of the upper vagina in a 17-year
      old German girl, who had a history of hypoplasia of the left kidney with an
      ectopic termination of the ureter in the upper vagina, removed surgically 2 years
      before. No previous report of a similar coincidence of vaginal clear cell
      carcinoma and a congenital disorder of the genitourinary tract exists. Congenital
      anomaly of the ureter interfering with the development and the differentiation of
      the distal Mullerian tract and its epithelium might have provided a similar
      histological basis for carcinogenesis in our patient to that in those provided
      exposed to DES.

PMID- 7529620
TI  - Metalloproteinase production by rabbit articular cartilage: comparison of the
      effects of interleukin-1 alpha in vitro and in vivo.
AB  - To assess the effects of interleukin-1 on intact To assess the effects of
      interleukin-1 on intact articular cartilage in vitro, explants from young and
      adult rabbits were cultured with interleukin-1 and the distributions of the
      matrix metalloproteinases and tissue inhibitor of metalloproteinases (TIMP-1)
      were investigated by indirect immunofluorescence microscopy. One to 2-week-old
      cartilage chondrocytes synthesized collagenase in response to pure or crude
      interleukin-1 (monocyte conditioned medium), with subarticular cells most
      responsive. Collagenase synthesis was not stimulated in adult articular
      chondrocytes when explants were treated with either pure or crude interleukin-1.
      Stromelysin, gelatinase and TIMP-1 could not be demonstrated within any zone of
      the cartilage, indicating that their synthesis was not stimulated by either pure
      or crude interleukin-1. The addition of fibroblast growth factors, either alone
      or in combination with interleukin-1, did not modify these responses. These
      results contrast markedly with observations on cultured chondrocyte monolayers,
      where interleukin-1 treatment induces near co-ordinate expression of
      metalloproteinases. To assess the effects of interleukin-1 in vivo, it was
      injected into adult rabbit knee joint spaces and the articular cartilage
      subsequently analysed for evidence of altered metalloproteinase production by
      immunocytochemistry. No significant increase in metalloproteinase or TIMP-1
      synthesis by chondrocytes was detected, although the cartilage matrix showed a
      marked loss of toluidine blue metachromasia. We conclude that metalloproteinases
      are not involved in the rapid loss of proteoglycan from cartilage matrix in these
      situations.

PMID- 7529626
TI  - Mouse pancreatic acinar/ductular tissue gives rise to epithelial cultures that
      are morphologically, biochemically, and functionally indistinguishable from
      interlobular duct cell cultures.
AB  - Most of the pancreatic exocrine epithelium consists of acinar and intralobular
      duct (ductular) cells, with the balance consisting of interlobular and main duct
      cells. Fragments of mouse acinar/ductular epithelium can be isolated by partial
      digestion with collagenase and purified by Ficoll density gradient
      centrifugation. We investigated whether previously developed culture conditions
      used for duct epithelium would result in the selective survival and proliferation
      of ductular cells from the acinar/ductular fragments. The fragments were cultured
      on nitrocellulose filters coated with extracellular matrix. After 2 to 4 wk the
      filters were covered with proliferating cells resembling parallel cultures of
      duct epithelium by the following criteria: protein/DNA ratio, light and electron
      microscopic appearance, the presence of duct markers (carbonic anhydrase [CA]
      activity, CA II mRNA, the cystic fibrosis transmembrane conductance regulator),
      the near absence of acinar cell markers (amylase and chymotrypsin), a similar
      polypeptide profile after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and the presence of spontaneous and secretin-stimulated
      electrogenic ion transport. Both duct and ductular epithelia formed fluid-filled
      cysts in collagen gels and both could be subcultured. We conclude that
      acinar/ductular tissue gives rise to ductular cells in culture by some
      combination of acinar cell death and/or transdifferentiation to a ductular
      phenotype, accompanied by proliferation of these cells and preexisting ductular
      cells. These cultures may be used to investigate the properties of this part of
      the pancreatic duct system, from which most of the pancreatic juice water and
      electrolytes probably originates.

PMID- 7529627
TI  - Current management of ventricular arrhythmias.
AB  - The last decade has seen dramatic developments in the management of ventricular
      arrhythmias, with new ideas about antiarrhythmic drug therapy and a growth in the
      use of implantable device therapy. This article reviews these changes and aims to
      provide a straightforward guide to the current management of ventricular
      arrhythmias.

PMID- 7529628
TI  - Risperidone: integrating research and practice.
AB  - Risperidone is a serotonin/dopamine antipsychotic which differs in important ways
      from established antipsychotics. This article highlights research findings
      relevant to clinical practice and points out differences between risperidone and
      established antipsychotics.

PMID- 7529630
TI  - Survey of family physicians: what is their role in cancer patient care?
AB  - In 1993, a survey of randomly-selected family physicians in two regions of
      Ontario was conducted to assess their views on various aspects of supportive care
      of patients with cancer. A response rate of 71% was obtained. Results showed that
      physicians are using preventive and screening techniques in their practices. They
      are comfortable with most of their roles in supportive cancer care with the
      exceptions of conveying news of therapy failure and total coordination of care.
      There is significant dissatisfaction with certain aspects of the timing and
      content of the consultation letters received from the regional cancer centers.
      Finally, family physicians expressed the importance of their roles in palliative
      care.

PMID- 7529629
TI  - A cancer and neutropenia database study.
AB  - The economic cost of treating febrile neutropenic cancer patients in Canada has
      not been defined. Amgen Canada Inc., the distributor of filgrastim (Neupogen
      Amgen Canada Inc.) was interested in determining this cost in order to evaluate
      the potential economic impact of filgrastim in the Canadian healthcare setting.
      Filgrastim is indicated to decrease the incidence of infection, as manifested by
      febrile neutropenia, in patients with nonmyeloid malignancies who receive
      myelosuppressive antineoplastic drugs. In addition, the company sought to
      determine which demographic factors influenced the cost. This was done to
      characterize which patients could derive clinical benefit from filgrastim while
      at the same time producing cost offsets through anticipated reductions in
      hospitalizations. In order to address these issues a study was commissioned to
      collect demographic data on patients diagnosed with both cancer and neutropenia
      in Canadian acute care hospitals. This cancer/neutropenia database was created
      from patient discharge abstracts contained in the 1990/91 Hospital Medical
      Records Institute national acute-care hospital database. The data presented in
      the HMRI report are consistent with the concept that subgroups of cancer patients
      exist in whom clinical benefits and cost off-sets may be realized from the use of
      growth factors.

PMID- 7529633
TI  - Steroid abuse in athletes, prostatic enlargement and bladder outflow obstruction-
      is there a relationship?
AB  - OBJECTIVE: To evaluate the effects of exogenous androgenic-anabolic steroids on
      the human prostate gland. SUBJECT AND METHODS: A white male athlete, who was
      routinely using anabolic steroids, volunteered for the study. He was studied
      during a 15-week period of steroid self-administration. Both objective and
      subjective parameters were measured, including: prostatic volume (transrectal
      ultrasound), digital rectal examination, urine flow rate, serum acid phosphatase
      and prostate specific antigen, symptom scoring for bladder outflow obstruction
      and other associated symptoms. RESULTS: During the period of steroid self
      administration, prostatic volume increased and urine flow rate decreased. The man
      also noticed an increase in nocturnal urinary frequency, libido and aggression.
      CONCLUSION: In this pilot study, the administration of exogenous androgenic
      anabolic steroids has been demonstrated to have profound effects on the human
      prostate gland, including an increase in prostatic volume, reduction in urine
      flow rate and an alteration in voiding patterns. These findings warrant further
      investigation.

PMID- 7529631
TI  - Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein,
      IGFBP-2, during demyelination induced by experimental autoimmune
      encephalomyelitis.
AB  - To assess the distribution of insulin-like growth-factor-related proteins during
      autoimmune CNS demyelination and remyelination, experimental autoimmune
      encephalomyelitis was produced by injecting Lewis rats with an emulsion
      containing guinea pig spinal cord and complete Freund's adjuvant. Tail weakness
      appeared at 10-12 days and was followed by hind and forelimb weakness. Paraplegia
      and incontinence were observed in some animals. From 8-40 days postinoculation
      (dpi), spinal cord sections were used to correlate lesion location and severity
      with mRNA distributions of insulin-like growth factor I (IGF-I), IGF-binding
      protein 2 (IGFBP-2), IGF-I-receptor (IGFR-I), glial fibrillary acidic protein
      (GFAP), and myelin basic protein (MBP). These were determined semiquantitatively
      by in situ hybridization. Fourteen dpi, there were inflammatory infiltrates and
      demyelination in both white matter (WM) and grey matter (GM). IGF-I and GFAP
      mRNAs were increased in these lesions and transcripts encoding myelin basic
      protein (MBP) were greatly reduced. Large lesions with extensive demyelination
      were evident in both WM and GM when mRNA levels of GFAP and IGF-I peaked 26 dpi.
      MBP mRNA levels began increasing 21 dpi and peaked 26 dpi, when a few thin
      regenerating myelin sheaths were found morphologically. Astrocytes, identified by
      their morphology and GFAP immunoreactivity, expressed very low levels of IGFBP-2
      mRNA and peptide in normal controls; their levels were significantly higher 14
      dpi, peaked 26 dpi, and then gradually decreased. Some neurons, as well as
      oligodendroglia in areas undergoing remyelination, expressed IGFR-I. Although
      levels of IGF-I, IGFBP-2, and GFAP mRNAs were highest in lesion areas, levels
      were also elevated around lesions and in some normal-appearing areas of WM and GM
      14-40 dpi. The gene expression of both IGF-I and IGFBP-2 by hypertrophic GFAP
      positive astrocytes was demonstrated 14-40 dpi by combined in situ hybridization
      and immunocytochemistry as well as by double immunostaining. Coexpression of IGF
      I and IGFBP-2 in the same astrocyte was a frequent finding. Relative increases in
      both IGF-I, GFAP, IGFBP-2, IGFR-I, and MBP mRNAs peaked at about the same time.
      This suggests that during lesion progression and recovery, astrocytic expression
      of IGF-I-related peptides may reduce immune-mediated myelin injury. We also
      suggest that astrocytic IGFBP-2 in lesions may help target IGF-I to IGFR-I
      expressing oligodendrocytes and promote remyelination of demyelinated axons.

PMID- 7529632
TI  - Antitumour effect of a synthetic analogue of fumagillin on murine renal
      carcinoma.
AB  - OBJECTIVE: To evaluate the antitumour effect of an angio-inhibitory drug, a
      synthetic analogue of fumagillin (TNP-470), on murine renal carcinoma (Renca) in
      vivo and in vitro. MATERIALS AND METHODS: The effect of TNP-470 on the growth of
      Renca cells in vitro was measured by angiogenesis assay and cell counting with
      dye exclusion. In the angiogenesis assay, Renca cells were injected intradermally
      and the number of blood vessels orientated towards the tumours was counted 3 days
      after tumour inoculation. To examine the effect of TNP-470 on the subcutaneous
      tumour growth and lung metastasis of Renca, Renca cells were injected
      subcutaneously or intravenously in BALB/c mice and they were treated with a
      subcutaneous injection every 3 days. RESULTS: Dose-dependent growth inhibition in
      vitro was observed with 50% inhibition occurring at 600 ng/ml. Angiogenesis assay
      revealed that administration of TNP-470 inhibited the angiogenesis induced by
      Renca in a dose-dependent manner. In the subcutaneous experiment, TNP-470
      decreased the growth rate of established subcutaneous tumours rather than reduced
      the size of the tumour. The administration of TNP-470 in mice with lung
      metastasis inhibited the development of metastasis of Renca without weight loss
      or diarrhoea. CONCLUSION: The present study demonstrated that TNP-470 had an
      inhibitory effect on tumour-induced angiogenesis and a significant anti-tumour
      effect on Renca. This suggests that TNP-470 could be useful in the treatment of
      renal cell carcinoma. Further studies are needed to clarify whether TNP-470 is
      more effective when combined with other drugs such as interferons.

PMID- 7529634
TI  - Nodular hyperplasia in the peripheral zone of the prostate gland.

PMID- 7529635
TI  - Liposomes that provide T-dependent help to weak antigens (T-independent
      antigens).
AB  - The design of an adjuvant for eliciting a thymus-dependent response to LPS, a
      well-defined thymus-independent antigen, is presented. Hybrid liposomes
      containing LPS and HA2 peptide from the hemagglutinin protein of influenza virus
      within the liposome bilayer were prepared (LPS/HA2 liposomes). The HA2
      polypeptide contains epitopes recognized by T-helper lymphocytes and T-cytotoxic
      lymphocytes. Outbred mice immunized with LPS/HA2 liposomes produced anti-LPS
      specific IgG responses. IgG subclass analysis indicated that IgG1, IgG2, and IgG3
      antibodies were produced by these animals. LPS liposomes (liposomes without HA2)
      stimulated a T-independent response only. This was demonstrated by the detection
      of IgG3 but not IgG1 or IgG2 in serum of mice immunized with LPS liposomes. These
      results support the concept that the simultaneous incorporation into liposomes of
      a polypeptide with T-cell recognition sites along with a T-independent antigen
      can lead to the generation of cognate T-cell help for the T-independent antigen.
      The synthesis and characterization of a neo-lipopolysaccharide T-independent
      antigen for incorporation in hybrid HA2 liposomes are also presented. Findings
      are discussed relative to the liposome model used and implications for
      development of vaccines for use in humans.

PMID- 7529638
TI  - Axon myelination. Myelination without myelin-associated glycoprotein.
AB  - Mice lacking myelin-associated glycoprotein surprisingly myelinate almost
      normally but their oligodendrocytes have lost their periaxonal cytoplasmic
      'collars' and accidentally myelinate already-myelinated axons.

PMID- 7529637
TI  - Expression of alpha 4 integrin mRNA and protein and fibronectin in the early
      chicken embryo.
AB  - alpha 4 integrins (alpha 4 beta 1 and alpha 4 beta 7) have been shown to mediate
      both cell-matrix adhesion to fibronectin and cell-cell adhesion to VCAM-1. These
      interactions have been suggested to contribute to hematopoiesis, lymphocyte
      homing, recruitment of inflammatory cells, neural crest cell migration and
      myogenesis. We report here the cloning of chicken alpha 4 cDNA and its use to
      define the patterns of expression of alpha 4 mRNA and protein in early chicken
      embryos (19-22 somite pairs), a stage at which neural crest cells can be examined
      at various points in their migration and somitic development and differentiation
      can also be observed at various stages. We observe widespread expression of both
      alpha 4 mRNA and protein, although the patterns of steady state expression do not
      conform precisely. Many neural crest cells contain significant levels of alpha 4
      mRNA. Some neural crest cells express alpha 4 protein but its expression is
      transient and/or limited to a subset of these cells. alpha 4 is strongly
      expressed at both mRNA and protein levels by somitic cells and their derivatives
      in the sclerotome, dermatome and myotome and is also expressed in neural tube,
      otic placode, heart, gut endoderm and some other tissues. Comparison with the
      distributions of fibronectin shows that, although some alpha 4 expression occurs
      in locations consistent with a role in cell-matrix adhesion to fibronectin, alpha
      4 is also expressed in other places where fibronectin is low or absent and a role
      for alpha 4 in cell-cell interactions appears more likely.

PMID- 7529636
TI  - Clones of tumor cells derived from a single primary human lung tumor reveal
      different patterns of beta 1 integrin expression.
AB  - Previously we reported that over 75% of human non-small cell lung cancers
      overexpress the beta 1 integrin VLA-2 on their surface and show an increase in
      the mRNA encoding the alpha-2 chain of this integrin. These results suggested the
      possibility that the overproduction and overexpression of one or more of the beta
      1 integrin may be involved in the pathogenesis of human lung tumors by modulating
      the invasive and/or metastatic potential of the tumor. We report here the
      generation and characterization of multiple clones of tumor cells derived from
      the primary culture of cells obtained from biopsy tissue of an aggressive human
      squamous cell lung tumor. We show that these tumor clones (or clonotypes) exhibit
      seven different yet stable phenotypes with respect to the expression of five
      members of the beta 1 integrin family. These results illustrate that a primary
      human lung tumor consists of multiple subpopulations of cells that while
      indistinguishable by ultrastructure are heterogeneous with respect to their beta
      1 integrins. The availability of these distinct tumor clonotypes derived from a
      single tumor biopsy have made it possible to test the assumption that the beta 1
      integrins play a role in tumor progression. The feasibility of this approach is
      demonstrated here by the intravenous inoculation of different human tumor
      clonotypes into severe combined immunodeficient (scid) mice. Our preliminary
      results with a pair of tumor clonotypes differing in VLA-1 and VLA-2 expression
      level reveal that the clonotype with high level of VLA-1 and VLA-2 displays a
      substantial increase in the experimental engraftment and metastasis of the human
      tumor cells in scid mice.

PMID- 7529639
TI  - Thyrotropin-releasing hormone enhances excitatory postsynaptic potentials in
      neocortical neurons of the rat in vitro.
AB  - Several lines of evidence suggest a modulatory effect of thyrotropin-releasing
      hormone (TRH) on synaptic transmission in the mammalian neocortex. In the present
      study, the effects of this tripeptide on intracellularly recorded neocortical
      pyramidal neurons were investigated using rat in vitro brain slice preparations.
      TRH (5 microM and 50 microM) added to the perfusion medium concentration
      dependently increased the excitability of pyramidal neurons, reflected by the
      number of spikes evoked by a depolarizing current pulse and by the augmentation
      of the time integral of glutamatergic excitatory postsynaptic potentials (EPSPs).
      TRH increased preferentially the time integrals of the late components of EPSPs
      (1-EPSPs) and increased their voltage-dependence. The early components of the
      EPSPs (e-EPSPs) were changed to much lesser extent. Iontophoretically applied D-2
      amino-5-phosphonovalerate (D-APV) antagonized the TRH-induced increase of the 1
      EPSPs. TRH also markedly enhanced the depolarizing responses evoked by
      iontophoretically applied N-methyl-D-aspartate (NMDA), while the depolarizing
      responses evoked by (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic
      acid (AMPA) and L-glutamate were not significantly affected. The depolarizing
      inward rectification present in all neurons studied was augmented by the higher
      concentration of TRH. The effects of TRH were incited after about 5 min and were
      long-lasting. In most neurons the effects of TRH on neuronal excitability did not
      completely recover during the 45 min washout period. The present data suggest
      that some of the non-hormonal actions of TRH in the neocortex may be due to an
      enhancement of glutamatergic synaptic transmission.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7529640
TI  - Immunohistochemical demonstration of nitric oxide synthase in the peripheral
      autonomic nervous system.
AB  - In the present immunohistochemical study the distribution of nitric oxide
      synthase (NOS) was studied in various autonomic ganglia and in related peripheral
      tissues of the rat. For comparison some other neuronal markers including
      acetylcholinesterase and tyrosine hydroxylase as well as several neuropeptides
      were analysed on adjacent or the same sections. The distribution of NOS-like
      immunoreactivity (LI) and of these other markers has been semiquantitatively
      summarized. In some parasympathetic ganglia such as the sphenopalatine and
      submandibular ganglia NOS-LI was present in most ganglion cells, at least partly
      coexisting with peptide histidine isoleucine (PHI), vasoactive intestinal
      polypeptide (VIP) and neuropeptide tyrosine (NPY). In the pelvic ganglia a
      comparatively smaller proportion of neurons was NOS-positive and they often
      contained VIP-LI and less frequently NPY-LI. In the tissues innervated by these
      ganglia, such as nasal mucosa and salivary glands, NOS-positive fibers were
      observed around blood vessels and within the glandular parenchyma, although
      generally less abundant than VIP/PHI nerves, while in the uterus, vas deferens
      and penis a more close correlation was seen. NOS-positive fibers were also widely
      distributed in other tissues. In the sympathetic ganglia NOS-LI was mainly
      present in dense fiber networks, which disappeared after transection of the
      sympathetic trunc central to the ganglion. Since many cell bodies in the
      sympathetic lateral column of the spinal cord also were NOS-positive, it is
      likely that the majority of preganglionic fibers innervating sympathetic ganglia
      are NOS-positive. VIP-positive cells in stellate ganglia did not contain NOS-LI.
      The present results suggest that NO may be a messenger molecule both in
      parasympathetic postganglionic neurons and in preganglionic sympathetic neurons.

PMID- 7529641
TI  - Descending projections from the superior colliculus to the reticular formation
      around the motor trigeminal nucleus and the parvicellular reticular formation of
      the medulla oblongata in the rat.
AB  - We observed by the anterograde and retrograde tracing techniques in the rat that
      the lateral part of the superior colliculus (SC), where the nigrotectal fibers
      from the dorsolateral part of the substantia nigra pars reticulata (SNr)
      terminated, sent projection fibers to the reticular region around the motor
      trigeminal nucleus (RFmt) and parvicellular reticular formation (RFp) of the
      medulla oblongata, where many premotor neurons for the orofacial motor nuclei
      were known to be distributed. The SC neurons sending their axons to the RFmt and
      RFp were mainly located in the stratum griseum intermedium, and additionally in
      the stratum griseum profundum. Our results suggest that neuronal signals conveyed
      through the nigro-tecto-bulbar pathway to the RFmt and RFp may exert control
      influences upon oral behavior.

PMID- 7529642
TI  - Bradykinin-evoked non-specific cationic current in neuroblastoma-glioma hybrid
      (NG108-15) cells and its down-regulation through differentiation.
AB  - Effects of bradykinin (BK) on the membrane conductance and level of cytoplasmic
      free Ca2+ in undifferentiated and differentiated neuroblastoma-glioma hybrid
      (NG108-15) cells were studied using the nystatin-perforated patch-clamp technique
      and fura-2 fluorometry. Under voltage clamp at -20 mV, undifferentiated cells
      responded to BK at > 10(-9) M, producing a biphasic current composed of an apamin
      sensitive Ca(2+)-activated K+ outward current and non-specific cationic inward
      current. Both current components corresponding to a biphasic elevation of [Ca2+]i
      were completely prevented by an intracellular perfusion with EGTA (1 mM) under
      conventional whole cell recording condition. Undifferentiated cells revealed
      almost no voltage sensitive Ca2+ current. In NG108-15 cells differentiated with 8
      Br-cyclic AMP (1 mM) or rolipram (1 mM), an inhibitor of type IV
      phosphodiesterase, BK concentration required for the non-specific cationic
      current with amplitude of > 100 pA was much greater than that of undifferentiated
      cells. This suggests that the differentiated cells decreased BK-sensitivity in
      induction of the non-specific cationic current. The non-specific cationic channel
      is suggested to play roles as a source of Ca2+ entry in undifferentiated NG108-15
      cells.

PMID- 7529643
TI  - N-methyl-D-aspartate receptor-mediated, prolonged afterdischarges of CA1
      pyramidal cells following transient cerebral ischemia in the rat hippocampus in
      vivo.
AB  - We previously reported the post-ischemic potentiation (PIP) of synaptic efficacy
      in hippocampal Schaffer collateral/CA1 responses of the rat beginning at 6-8 h
      following 12 min transient cerebral ischemia in vivo. The present study
      demonstrated that repetitive stimulation with a relatively low frequency (5 Hz, 6
      s), which produced short-lasting afterdischarges (ADs; duration, 4.49 +/- 4.26 s;
      n = 7) in sham-controls, resulted in prolonged ADs (duration, 26.33 +/- 12.63 s;
      n = 6; P < 0.001) at the same period after ischemia. The PIP was not affected by
      2-amino-5-phosphonovalerate (APV) administered via microdialysis at 7 h post
      ischemia. The prolonged ADs in response to repetitive stimulation were, however,
      reversed to short-lasting ADs (duration, 7.13 +/- 1.44 s; n = 4; P < 0.02) by the
      same procedure, leaving the response to single stimulation unaffected. These
      findings suggest that, during the reperfusion period, Ca2+ influx into the CA1
      pyramidal cells can be greatly increased through N-methyl-D-aspartate (NMDA)
      receptor-coupled ion channels if appropriately timed multiple synaptic inputs
      bombard these cells. Such Ca2+ influx may contribute to delayed death of CA1
      pyramidal cells after transient cerebral ischemia if synaptic activity is
      maintained at relatively high levels during the reperfusion period.

PMID- 7529644
TI  - Fas antigen mRNA induction in postischemic murine brain.
AB  - Fas antigen mRNA induction in the brain was examined using a transient global
      cerebral ischemia model in BALB/C mice. Northern blot analysis revealed little
      Fas antigen mRNA expression in the brains of sham-operated mice. A marked
      induction of Fas mRNA expression was detected in the brains of mice 6 h after 30
      min of cerebral ischemia. These results suggest a possible apoptotic mechanism
      for cell death, mediated by the Fas antigen, in postischemic brain.

PMID- 7529645
TI  - Nitric oxide synthase-immunoreactive nerve fibers in the nasal mucosa of the rat.
AB  - An immunohistochemical study was performed to detect the localization of nitric
      oxide synthase (NOS) in the rat nasal mucosa by light and electron microscopy.
      NOS-immunoreactive nerve fibers were observed around blood vessels and seromucous
      glands. They were found in the subepithelial layer and even within the
      epithelium. But no NOS-immunoreactivity was found in the olfactory
      neuroepithelium. Electron microscopy showed that NOS-immunoreactive nerve
      profiles were in close contact with the cytolemma of respiratory epithelial cells
      and acinar cells of seromucous glands. NOS-immunoreactive axon varicosities were
      located at a considerable distance from the smooth muscle of arterioles and small
      veins as well as the endothelial cells of venules and capillaries. We confirmed
      that NOS-containing nerves innervated the epithelium, blood vessels and
      seromucous glands of the nasal mucosa. These findings, collectively, suggested
      the possibility that nitric oxide participated in the sensory function of the
      epithelium, the secretory activities of the nasal gland, and the regulation of
      vascular tone and vascular permeability in the nasal mucosa.

PMID- 7529647
TI  - A putative retinohypothalamic projection containing substance P in the human.
AB  - The retinohypothalamic tract (RHT) is the principal pathway mediating the
      entraining effects of light on the circadian pacemaker, the suprachiasmatic
      nucleus (SCN). In the rat, the RHT has two components, one which projects to the
      SCN and the intergeniculate leaflet of the thalamus and has no known peptide
      content and one which projects to the SCN and, perhaps, to the olivary pretectal
      nucleus and contains substance P (SP). Both terminate predominantly in a zone of
      the SCN that contains vasoactive intestinal polypeptide (VIP)-producing neurons.
      In the human, there is a similar dense axonal plexus of SP-immunoreactive axons
      in the SCN located largely in the area occupied by VIP-immunoreactive neurons and
      distinct from other SP-immunoreactive axons in the area. We propose that this SP
      plexus represents a component of the RHT in the human brain.

PMID- 7529648
TI  - Intracarotid infusion of bradykinin selectively increases blood-tumor
      permeability in 9L and C6 brain tumors.
AB  - This study investigated the effects of bradykinin on blood-tumor barrier (BTB)
      permeability in transplanted 9L gliosarcomas (9L) and C6 gliomas (C6) in rats.
      Permeability, expressed as the unidirectional transfer constant, Ki
      (microliter/g/min), was measured by quantitative autoradiography. Tracers used to
      examined permeability included radiolabeled alpha-aminoisobutyric acid
      ([14C]AIB), sucrose ([14C]sucrose) and dextran ([14C]dextran). Intracarotid
      infusion of bradykinin (10 mg/kg/min) significantly increased the BTB
      permeability in both 9L and C6 tumors to [14C]AIB and [14C]sucrose, but did not
      increase permeability to [14C]dextran. Blood-brain barrier (BBB) permeability in
      normal (non-tumor) brain was not significantly increased to any of the tracers by
      intracarotid bradykinin infusion. Ki values for [14C]AIB, [14C]sucrose and
      [14C]dextran of 9L tumors in the bradykinin group versus control group were 41.6
      +/- 12.6 vs. 24.8 +/- 6.30 (P < 0.02), 17.5 +/- 9.34 vs. 9.05 +/- 4.36 (P <
      0.05), and 3.90 +/- 2.59 vs. 2.42 +/- 1.76, respectively (mean +/- S.D.). Ki
      values to [14C]AIB, [14C]sucrose and [14C]dextran of C6 tumors in the bradykinin
      group versus control group were 41.4 +/- 19.0 vs. 19.5 +/- 11.4 (P < 0.01), 18.0
      +/- 8.88 vs. 7.06 +/- 3.05 (P < 0.01), and 4.07 +/- 1.45 vs. 2.27 +/- 1.26,
      respectively (mean +/- S.D.). Intracarotid infusion of bradykinin did not
      significantly increase the blood volume in tumor or brain tissue despite its
      known vasodilative effect. Intracarotid infusion of bradykinin may be a useful
      technique for selective delivery of compounds to brain tumors.

PMID- 7529649
TI  - Neurons projecting from the entopeduncular nucleus to the thalamus receive
      convergent synaptic inputs from the subthalamic nucleus and the neostriatum in
      the rat.
AB  - The two major afferents of the entopeduncular nucleus are the subthalamic nucleus
      and the neostriatum, which have opposing physiological effects on entopeduncular
      neurons. Experiments were performed to test the hypothesis that individual
      entopeduncular neurons that project to the thalamus receive convergent synaptic
      input from both the subthalamic nucleus and the neostriatum in the rat. This was
      achieved using double anterograde tracing combined with retrograde tracing. In
      the electron microscope anterogradely labelled subthalamic (Subthalamic Type 1)
      and neostriatal terminals were observed to form asymmetrical and symmetrical
      synaptic contacts respectively, with all parts of entopeduncular neurons.
      Labelled subthalamic and neostriatal terminals were observed in convergent
      synaptic contact with entopeduncular neurons, some of which were retrogradely
      labelled from the thalamus. A second rarer type of terminal was labelled
      (Subthalamic Type 2) which formed symmetrical synaptic contacts with the proximal
      regions of unlabelled and retrogradely labelled entopeduncular neurons. These
      terminals are believed to be derived from the globus pallidus. It is concluded
      that the topographical and synaptic organization of the so-called direct
      (neostriatum to entopeduncular nucleus) and indirect pathways (involving the
      subthalamus and the globus pallidus) is capable of mediating the inhibition and
      excitation of output neurons in the entopeduncular nucleus that occur following
      neostriatal stimulation.

PMID- 7529650
TI  - The role of nitric oxide in the neuropathology in soman intoxication.
AB  - Intoxication with organophosphorus (0P) anticholinesterase agents such as soman
      triggers irreversible lesions in some cerebral areas. Administration of soman at
      the LD 50 leads to an increased activity of NADPH-diaphorase (= NO-synthase) in
      the cerebral endothelial cells from the 6th hour after poisoning. This activity
      culminates after 24 h, whereas variations in this enzymatic activity are not
      easily detectable in NADPH-diaphorase positive neurons. Since soman triggers
      astrocytic oedema leading to a possible decrease in the local cerebral blood
      flow, it is likely that the induction of endothelial NO-synthase exerts an
      antagonistic effect, since NO is a vasodilator.

PMID- 7529646
TI  - Localization of vitronectin- and fibronectin-receptors on cultured human glioma
      cells.
AB  - Utilizing a human astrocyte-derived glioma cell line, we have demonstrated the
      presence of a vitronectin receptor, alpha v beta 3, and a fibronectin receptor,
      alpha 5 beta 1, on the surface of the cells spreading on the respective adhesion
      molecules by immunohistochemical analyses. By phase-contrast microscopy, these
      receptors were found to be expressed predominantly in the focal contact-like
      area, suggesting that they were involved in the spreading of the cells upon
      contact with these adhesion molecules. Interestingly, they appeared to have
      differential functions and roles as integrins as evidenced by different time
      dependent distribution profiles on the cell surface in the serum-containing
      medium. Furthermore, both vitronectin and fibronectin seem to have chemotactic
      effects onto the glioma cells as observed in a Boyden chamber study. Although
      these receptors are not expected to be present on the surface of astrocytes under
      physiological conditions, they may be expressed thereon and involved in gliosis
      when the cerebral vasculature is traumatized and, thereby, blood proteins,
      including vitronectin and fibronectin, come into contact with the astrocytes.

PMID- 7529651
TI  - Substance P nerve terminals synapse upon negative chronotropic vagal motoneurons.
AB  - Previous data indicate that there are anatomically segregated and physiologically
      independent parasympathetic ganglia on the surface of the heart which are capable
      of selective control of sino-atrial rate, atrio-ventricular conduction, and
      atrial contractility. We have injected a retrograde tracer into the cardiac
      ganglion which selectively regulates heart rate (the SA ganglion). Medullary
      tissues were processed for the histochemical visualization of retrogradely
      labeled neurons and for the immunohistochemical detection of the neurotransmitter
      substance P (SP) by dual labeling light and electron microscopic methods.
      Negative chronotropic retrogradely labeled cells were found in a long slender
      column in the ventrolateral nucleus ambiguous (NA-VL) which enlarged somewhat at
      the level of the area postrema. These cells were found bilaterally, but they were
      asymmetrically distributed. Half the animals showed a pronounced right side
      predominance in retrograde labeling, while the other half of the animals showed a
      lesser left side predominance. These observations may help to explain some of the
      controversy in the literature concerning the relative influence of the right and
      left vagus nerves on sinus rate. Ultrastructural examination demonstrated axo
      somatic and axo-dendritic contacts between SP nerve terminals and retrogradely
      labeled negative chronotropic NA-VL neurons. SP immunoreactivity was often
      associated with large dense-core vesicles in terminals forming either symmetric
      or asymmetric synapses. These observations provide a potential anatomical
      substrate for the centrally mediated bradycardia elicited by microinjections of
      SP into the NA. SP immunoreactive terminals were also observed to make axo
      somatic, axo-dendritic, and axo-axonic synapses with unlabeled neurons in NA
      VL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529652
TI  - Acute neurite retraction triggered by lysophosphatidic acid: timing of the
      inhibitory effects of genistein.
AB  - Acute neurite retraction, elicited by diverse agents in several neuronal cell
      types, has been reported to be inhibited by genistein, a kinase antagonist that
      is relatively (though not absolutely) selective for tyrosine kinases. It was
      hypothesized that genistein acts upon some final common pathway that integrates
      multiple extrinsic and intrinsic signals to regulate whether neurites will
      execute a retraction response (J. Neurochem., 61 (1993) 340-343). To define this
      pathway in more detail, a quantitative study of NG108-15 cell rapid-onset
      neurites was carried out as they retract in response to lysophosphatidic acid
      (LPA, 10 microM). Following the application of LPA, most neurites exhibited early
      morphologic changes between 0.5 and 1.5 min, followed by progressive shortening
      and eventual retraction, with 50% of neurites completely retracted by 5 min and
      80% gone by 10 min. Genistein did not inhibit the formation of subcortical F
      actin, nor its functional competence in several assays. Genistein protected
      neurites when added at any time prior to the onset of the earliest morphologic
      changes, but failed to block progression when added to neurites that were already
      undergoing retraction. These findings imply that the final common pathway (i.e.
      the critical target(s) for genistein) must be activated late, after the increase
      in F-actin levels has peaked and just before retraction is initiated.

PMID- 7529653
TI  - Intracerebroventricular injection of dibutyryl cyclic adenosine 3',5'
      monophosphate increases hypothalamic levels of neuropeptide Y.
AB  - This investigation examined in vivo the relationship between the nucleotide cAMP
      and hypothalamic levels of two peptides, neuropeptide Y (NPY) and galanin (GAL),
      which are known to potentiate feeding behavior. In brain-cannulated rats, third
      ventricular injections of N6,2'-O-dibutyryl cyclic adenosine 3',5'-monophosphate
      ((Bu)2cAMP, 25 micrograms), compared to saline, caused a significant increase in
      NPY levels in the arcuate nucleus (ARC) and medial parvocellular portion of the
      paraventricular nucleus (mPVN), while having no impact in other hypothalamic
      areas. These site-specific changes in NPY occurred in the absence of any
      alteration in circulating levels of insulin, corticosterone, aldosterone or
      glucose, or of changes in hypothalamic levels of GAL. These findings implicate
      cAMP as having regulatory functions within specific hypothalamic NPY-synthesizing
      neurons, projecting from the ARC to the mPVN, that are believed to be involved in
      energy homeostasis.

PMID- 7529656
TI  - Non-osseous complications following distal radius fractures.

PMID- 7529655
TI  - Fetal marrow suppression after maternal chemotherapy for leukaemia.
AB  - A preterm baby, whose mother received chemotherapy for acute leukaemia during
      pregnancy, required intensive care because of profound anaemia and neutropenia.
      Haemopoietic progenitor cell studies showed fetal marrow suppression. Those
      caring for such mothers and babies should know the possible serious effects
      chemotherapy for malignancies can have on a developing fetus. Long term follow up
      of the baby is imperative.

PMID- 7529657
TI  - Histomorphometric study of mast cells in normal bone, osteoporosis and
      mastocytosis using a new stain.
AB  - A new stain for mast cells (Mc) in bone was applied in 9 normal, 14 osteoporotic,
      and 1 case of systemic mastocytosis. Examination included the following
      calculations: Mc counts according to various area and perimetry referents
      including cortical (Ct) and cancellous (Cn) components; proportion of Mc types;
      and diameter and area of ovoid Mc. The following findings were noted: (1) in all
      groups, Mc counts were higher in the Ct compared with Cn bone, and Mc counts
      correlated with type but not size of Mc; (2) in osteoporotics compared with
      normals, Mc counts were higher in Cn but not Ct bone for both area and perimetry
      referents; (3) a lower proportion of ovoid Mc were seen in osteoporotics; (4) two
      cases of osteoporosis had similar Mc counts to a case of mastocytosis, but the
      latter had a higher proportion of spindle- and bizarre-shaped Mc and a higher
      proportion of Mc in contact with the bone surface. The Mc by virtue of an
      increase in number, closer contact with bone surface, and pattern of
      morphological types may have a role in osteoporosis in occasional instances.

PMID- 7529659
TI  - Teaching older adults by adapting for aging changes.
AB  - Few teaching programs are geared to meet the special learning needs of the
      elderly. This pilot study used a quasi-experimental pretest-posttest design to
      measure the effect of the Adaptation for Aging Changes (AAC) Method on fecal
      occult blood screening (FOBS) at meal sites for the elderly in the South. The AAC
      Method uses techniques that adjust the presentation to accommodate for normal
      aging changes and includes a demonstration of the procedure for collection of the
      stool blood test, memory reminders of the date to return the stool blood test,
      and written materials adapted to the 5th grade reading level. In addition, actual
      practice of the FOBS with the use of peanut butter was added to the AAC Method,
      making it the AAC with Practice Method (AACP) in two sites. The American Cancer
      Society's colorectal cancer educational slide-tape show served as the basis for
      all of the methods. Hemoccult II kits were distributed at no cost to the
      participants. Descriptive statistics, chi 2, and logistic regressions were used
      to analyze data from 135 Council on Aging meal sites' participants. The average
      age of the participants was 72 years; the average educational level was 8th
      grade; over half the sample was African-American; and half of the participants
      had incomes below the poverty level. Results support a significant increase in
      participation in FOBS in participants taught by the AACP Method [chi 2 (1, n =
      56) = 5.34, p = 0.02; odds ratio = 6.2]. This research provides support for
      teaching that makes adaptations for aging changes, especially adaptations that
      include actual practice of the procedure.

PMID- 7529654
TI  - Effect of substance P and protein kinase inhibitors on beta-amyloid peptide
      induced proliferation of cultured brain cells.
AB  - The present study investigated the effect of substance P (SP) and protein kinase
      inhibitors (H7 and HA1004) on beta-amyloid peptide-induced proliferation of
      neonatal rat brain cells in primary cultures. The beta-amyloid peptide1-28
      (designated as beta AP28), at nanomolar concentrations (10(-9) M), significantly
      (P < or = 0.05) increased the proliferation of brain cells (presumably non
      neuronal) as measured by [3H]thymidine uptake into DNA (mitogenesis). The effect
      was dependent on time of culture, concentration of beta AP28, and presence of
      fetal calf serum. The supplementation of SP into cell cultures at time zero
      reversed the proliferative response of beta AP28. Moreover, the beta AP28-induced
      proliferation was inhibited by protein kinase inhibitor H7, but not by HA1004.
      Since H7 is a selective protein kinase C (PKC) inhibitor and SP action involves
      PKC, we conclude that beta AP28 induces normal brain cell proliferation through
      PKC pathway of cell signaling.

PMID- 7529658
TI  - Ultrastructure of hypertrophic cartilage: histochemical procedures compared with
      high pressure freezing and freeze substitution.
AB  - The effect of cationic dyes on the ultrastructure of hypertrophic cartilage was
      compared with results obtained with modern cryotechniques in studies on rat
      epiphyseal growth plate. Addition of alcian blue, acridine orange, cupromeronic
      blue, ruthenium hexamine trichloride, ruthenium red, or safranin O to
      conventional glutaraldehyde/osmium tetroxide fixatives to a large extent resulted
      in prevention of chondrocyte shrinkage except for alcian blue which showed poor
      tissue penetration. The fine structure of the matrix in pericellular and
      territorial compartments appeared very coarse with areas of high contrast in
      tissue exposed to fixatives containing cationic dyes. This indicates structural
      collapse and precipitation of electron-dense material, a pattern clearly
      differing from that observed in specimens prepared by the cryotechniques. The
      dyes giving a pattern most similar to that seen after high pressure freezing,
      freeze substitution, and low temperature embedding were acridine orange and
      safranin O. It is concluded that studies of matrix ultrastructure down to the
      molecular level necessitate the application of cryotechniques.

PMID- 7529661
TI  - Light-dependent induction of early-response gene expression by calphostin-C.
AB  - Calphostin-C is a compound possessing the ability to inhibit protein kinase C
      (PKC) by oxidative modification in vitro and to enhance the epidermal growth
      factor (EGF) receptor phosphorylation in vivo in a light-dependent manner. Here,
      we found that calphostin-C induced c-fos and c-jun mRNA accumulation in the lung
      adenocarcinoma cell line A549 in a light-dependent manner. Nuclear run-on assay
      revealed that this mRNA accumulation took place at the transcription level.
      However, unlike in vitro, calphostin-C did not inhibit cytosolic PKC activity in
      vivo, and the gene expression induced by calphostin-C was inhibited by another
      PKC inhibitor, staurosporine. Thus, it was suggested that calphostin-C activates
      cytosolic PKC-dependent signaling pathway to the induction of "early-response
      gene" expression in a light-dependent manner.

PMID- 7529660
TI  - Permanent indwelling peritoneal access device for the management of malignant
      ascites.
AB  - The case presented demonstrates an alternative management approach for malignant
      ascites. A permanent indwelling peritoneal port for at-home, small-volume
      paracentesis, provided palliative therapy for a patient who had malignant ascites
      secondary to breast cancer. The device allowed paracentesis without the risk of
      repetitive peritoneal puncture or diuretic therapy.

PMID- 7529662
TI  - Microcephaly with large anterior fontanelle, generalized convulsions, micropenis,
      and distinct anomalies of the hands and feet. Another example of Wiedemann
      syndrome?
AB  - Wiedemann et al. (1985) described a rare syndrome characterised by microcephaly,
      psychomotor delay, short stature, short fingers and toes with stubby broad thumbs
      and halluces. Unilateral undescended testis, inguinal hernias, scrotal
      hypoplasia, and micropenis were also features. They described two males, first
      cousins, whose mothers and maternal grandfather had short broad thumbs and
      halluces. We report a male with identical features whose parents were normal.
      This is only the second report of this syndrome. Autosomal or X-linked dominant
      inheritance is most likely.

PMID- 7529663
TI  - Complex chromosomal rearrangements: some breakpoints may have cellular adaptive
      significance.
AB  - Cytogenetic study of a 3-year-old girl with developmental delay and some minor
      abnormalities revealed a complex chromosome rearrangement (CCR) involving seven
      chromosomes with eight breakpoints, leading to monosomy of segment 5q15-q22.
      According to breakpoint distribution, CCRs may be classified as those with
      primary intrachromosomal abnormalities (including inversions, insertions,
      duplications, etc.) and those without them. Only the latter group of CCRs was
      used in this analysis. Comparison of theoretical and observed breakpoint
      distributions in 33 cases demonstrated that recurrent involvement of some
      chromosome(s) ("re-entry") occurs more frequently than expected. One possible
      explanation for this observation suggests that the initial event leads to an
      unstable provisional rearrangement, and subsequent breaks are necessary to
      stabilize the karyotype.

PMID- 7529665
TI  - Effects of cyclic nucleotide phosphodiesterase IV inhibitor, Ro20,1724, on
      pancreatic exocrine secretion in dog.
AB  - 1. The effects of the cyclic nucleotide phosphodiesterase (PDE) inhibitors,
      Ro20,1724, 3-isobutyl-1-methylxanthine (IBMX), trifluoperazine (TFP) and amrinone
      on pancreatic exocrine secretion were investigated in anaesthetized dogs in
      comparison with those of secretion and cholecystokinin octapeptide (CCK-8). 2.
      Ro20,1724 (1-30 nmol/kg), IBMX (3-30 nmol/kg), secretin (0.01-0.1 pmol/kg) or CCK
      8 (0.1-1 pmol/kg) injected i.a. elicited a dose-dependent increase in the
      secretion of pancreatic juice, but TFP and amrinone (up to 1 mumol/kg) did not.
      3. The bicarbonate concentration in pancreatic juice was increased and the
      protein concentration was decreased by Ro20,1724, IBMX and secretin.
      Cholecystokinin octapeptide increased the protein concentration but did not alter
      the bicarbonate concentration. 4. Ro20,1724 and IBMX elicited more than the
      respective additive secretory response when added together with secretin,
      although the stimulatory effects of CCK-8 with Ro20,1724 and IBMX were additive.
      5. Ro20,1724 and IBMX increased cyclic AMP concentration but did not affect
      cyclic GMP concentration. 6. These results suggest that Ro20,1724 and IBMX have
      secretory properties on pancreatic exocrine glands of the dog, which may be
      mediated through an increase in cyclic AMP subsequent to inhibition of PDE
      activity. Furthermore, pancreatic PDE enzymes in the dog may be mainly type IV.

PMID- 7529666
TI  - Adhesion of carcinoma cells to rat hepatocytes and rat fibronectin is inhibited
      by the OPAR monoclonal antibody, which is directed against a rat liver-specific
      carbohydrate epitope.
AB  - The OPAR mouse monoclonal antibody (mAb) directed against rat hepatocytes was
      previously shown to inhibit adhesion of TA3/Ha mammary carcinoma cells to
      hepatocytes. The antigen is abundantly present at the surface of hepatocytes
      beneath the endothelium of liver capillaries where we have observed invasion of
      carcinoma cells to occur. The OPAR mAb reacted with three major bands on a
      Western blot of liver plasma membrane proteins. The same proteins were also seen
      upon immunoprecipitation from iodinated liver plasma membrane proteins. We have
      isolated OPAR antigens by lectin wheat germ agglutinin (WGA) and OPAR affinity
      chromatography. Amino acid sequence analysis revealed that two of the bands were
      alpha 1-macroglobulin and C4-binding protein, which are serum components produced
      by hepatocytes. The presence of the epitope on distinct proteins and our previous
      observation that it can be detected in the Golgi apparatus but not in the
      endoplasmic reticulum, suggested that OPAR reacts with a liver-specific
      glycoconjugate. Loss of OPAR reactivity after neuraminidase and N-glycosidase F
      treatment showed that the epitope contains sialic acid residues on N-linked sugar
      moieties. OPAR also reacted with rat fibronectin, and inhibited adhesion of
      TA3/St cells to fibronectin. This explains the inhibition by the OPAR mAb of
      TA3/St cell adhesion to hepatocytes, which we have shown to be due mainly to
      interaction with hepatocyte surface-associated fibronectin. However, adhesion of
      the related TA3/Ha cells to hepatocytes, which is mediated by the alpha 6 beta 4
      integrin, and does not involve binding to fibronectin, is also inhibited. This
      suggests that alpha 6 beta 4 on liver-metastasizing carcinoma cells binds to an
      OPAR epitope-carrying glycoprotein produced by hepatocytes.

PMID- 7529664
TI  - Haemodynamic actions of a nitric oxide (EDRF) synthesis inhibitor in conscious
      baboons (Papio hamadryas).
AB  - 1. The haemodynamic effects of intravenous nitric oxide inhibitor, N-nitro-L
      arginine (NOLA), were examined in four conscious non-restrained baboons (Papio
      hamadryas). Mean arterial pressure, (MAP), systemic vascular resistance (SVR) and
      cardiac output (CO) were measured at timed intervals up to 24 h after a bolus
      injection of NOLA. 2. N-nitro-L-arginine increased blood pressure in a dose
      dependent manner up to 9.5 mg/kg. Increases in blood pressure were accompanied by
      increases in SVR and decreases in CO, with a significant fall in heart rate. 3.
      One animal received 9.5 mg/kg NOLA and became unconscious, suggesting cerebral
      vasospasm. 4. Vascular effects of nitric oxide contribute significantly to the
      regulation of arterial blood pressure under physiological conditions in the
      baboon.

PMID- 7529667
TI  - [Human papillomavirus infections in pregnancy].
AB  - After an overview on the diffusion and transmission of the Human Papilloma Virus
      infection, the authors' attention is focused on clinical and therapeutic aspects
      of the disease. Following the most recent findings on congenital transmission,
      problems related to prophylaxis and therapy are discussed.

PMID- 7529668
TI  - [Palliative therapy of malignant bile duct stenoses].
AB  - The majority of patients (up to 80%) with malignant obstructive jaundice will not
      be eligible for curative treatment. Palliative treatment of choice is the
      percutaneous or endoscopic placement of endoprostheses with a low periprocedural
      morbidity and mortality. The development of expandable metallic stents led to
      improved patency rates compared to plastic endoprostheses. Reocclusion rates of
      approximately 20%, however, necessitate further improvements to optimize design
      and materials of these stents.

PMID- 7529669
TI  - [Radiotherapy of malignant obstructive jaundice].
AB  - Brachytherapy using the afterloading technique with iridium 192 and percutaneous
      irradiation using 16 MV photons are used for the irradiation of malignant
      obstructive jaundice. Mostly, however, a combination of both methods can be used
      to advantage. In bile duct tumors and Klatskin tumors, the endoluminal part can
      be treated using brachytherapy. The extralumenal growth and, if necessary, all
      affected regional lymph node areas can be treated by a 3D planned, percutaneous,
      moving field technique. Intraoperative radiotherapy can be used in a few cases as
      booster irradiation of tumor conglomerates at the porta hepatis. The decision to
      use irradiation must be made very carefully since solid tumors are usually
      involved that require a high target dose, the application of which can lead to
      unacceptable side effects. The radio-oncological spectrum is therefore confined
      predominantly to palliative therapy.

PMID- 7529670
TI  - [Palliative surgical and endoscopic therapy of malignant bile duct occlusion].
AB  - Cholestatic jaundice is the result of a malignancy of the bile duct itself, of
      the gallbladder, of the ampulla or (as in most cases) of the pancreas. Patients
      without evidence of metastases or other signs of advanced cancer (e.g. ascites)
      are candidates for explorative laparotomy. In the vast majority of cases
      resection of a tumor is not feasible and the surgeon is faced with the objective
      of providing palliation. To date there exists not only one palliative procedure,
      and the surgeon has to take into account the following: In patients with
      pancreatic cancer palliation can be given with biliary bypass with or without
      gastroenterostomy. This carries an operative mortality of almost 20% and means a
      survival of only 5-6 months. Nonsurgical procedures as transpapillary stenting
      play an increasing role in the management of patients with obstructive jaundice
      due to pancreatic cancer. In some cases however resectable tumors perhaps will be
      overlooked. The results of controlled studies comparing endoscopic stenting and
      surgical bypass are encouraging for stenting techniques (lower morbidity and
      mortality (< 10%), technical success rates exceeding 90%). The availability of
      different palliative treatment modalities for carcinoma of the bile ducts
      suggests that no approach is definitely superior. Operative biliary-enteric
      anastomosis gives a tolerable operative mortality rate in younger patients, less
      morbidity, than external biliary drainage by better quality of life of the
      patients. In retrograde placement of prosthetic stents, in patients with high
      bile duct obstruction difficulties are frequently. In such cases the percutaneous
      drainage should be reserved for endoscopic failures, in cases the endoscopic and
      percutaneous approaches can be combined in the 'rendezvous' procedure. In recent
      years several reports have advocated extensive surgery for biliary neoplasms.
      Preoperative staging of these patients remains an issue as none of the commonly
      modalities are accurate in predicting resectability.

PMID- 7529671
TI  - Rabbit and ferret parietal cell inhibition by Helicobacter species.
AB  - We tested sonicates of Helicobacter pylori, H. mustelae, and H. felis for
      inhibition of acid secretion in rabbit and ferret isolated gastric glands. Three
      H. pylori strains, two of three H. mustelae strains, and two H. felis strains
      significantly inhibited acid secretion in rabbit cells by 95.2-93.3%, 55.9% and
      96.4%, and 83.4-96%, respectively. All Helicobacter strains examined inhibited
      acid secretion by ferret cells by 65.3-76.8%, 89.1-97.6%, and 85.8-92.8%. H.
      pylori inhibited acid secretion after stimulation with histamine and
      isobutylmethylxanthine or with 8-bromo-cyclic adenosine monophosphate (P < 0.05
      for all tests). These findings demonstrate that acid inhibition is a property
      common to the three Helicobacter species tested. It occurs independently of the
      mammalian origin of the parietal cell, and it does not involve blockade of
      histamine-2 receptors.

PMID- 7529673
TI  - Hepatitis C virus infection as a determinant of behavior in type 1 autoimmune
      hepatitis.
AB  - To determine if hepatitis C virus infection influences the behavior of type 1
      autoimmune hepatitis and to assess the performance parameters of third-generation
      immunoassays for viral infection in this disease, 64 patients with different
      patterns of disease behavior were assessed retrospectively for antibodies to
      hepatitis C virus by third-generation enzyme-linked immunosorbent assay and
      recombinant immunoblot assay and for HCV RNA by polymerase chain reaction.
      Hepatitis C virus RNA was detected in seven patients (11%) and antibodies to
      hepatitis C virus were found in five (8%). All patients who had an acute onset of
      illness or who sustained remission after therapy lacked HCV RNA in serum. In
      contrast, four of 31 patients who relapsed (13%) and three of 17 patients who
      failed treatment (18%) had HCV RNA in serum. Patients with HCV RNA were
      indistinguishable from those without HCV RNA; in three patients, infection was
      recognized only by testing for HCV RNA. Four of seven patients with HCV RNA
      responded fully to corticosteroids, although each relapsed after drug withdrawal.
      Smooth muscle antibodies (43% versus 91%, P = 0.006) and concurrent smooth muscle
      and antinuclear antibodies (0% versus 60%, P = 0.003) occurred less frequently in
      patients with HCV RNA than in counterparts without HCV RNA. The specificity of
      the third-generation enzyme immunoassay was 98% and its overall predictability
      was 94%. Its sensitivity, however, was 57% and false positive results occurred in
      20%. Hepatitis C virus infection is an uncommon determinant of disease behavior
      in type 1 autoimmune hepatitis, but it may be present in relapse or treatment
      failure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529672
TI  - Up-regulation of E-selectin and intercellular adhesion molecule-1 differs between
      Crohn's disease and ulcerative colitis.
AB  - In present study, we investigated if inflammatory mediators secreted by the
      inflamed colonic mucosa from patients with Crohn's disease and ulcerative colitis
      had the ability to up-regulate the expression of two adhesion molecules, E
      selectin and intercellular adhesion molecule-1. Organ culture techniques and
      enzyme-linked immunoassays were used to quantify these up-regulations in human
      umbilical vein endothelial cells. Our results show that, in Crohn's disease
      patients, the expression of E-selectin was up-regulated 5.5-fold over control
      values and intercellular adhesion molecule-1 expression was increased 2.4-fold.
      In ulcerative colitis patients, E-selectin expression was up-regulated twofold
      over controls with only a 1.5-fold increase in intercellular adhesion molecule-1
      expression. Histologically, there was no difference in the degree of inflammation
      between the two disease groups. Sulfasalazine, in a dose-dependent manner,
      inhibited E-selectin expression up to 58% and intercellular adhesion molecule-1
      up to 62% when stimulated by lipopolysaccharide. The up-regulation of E-selectin
      and intercellular adhesion molecule-1 may play an important role in mediating the
      inflammatory process in inflammatory bowel disease. The observed difference
      between Crohn's disease and ulcerative colitis may reflect differences in
      inflammatory cell infiltrates or the histopathological differences between the
      two diseases.

PMID- 7529676
TI  - Impaired axonal transport in diabetic neuropathy.

PMID- 7529674
TI  - Evidence for hepatitis B virus infection in patients with chronic hepatitis C
      with and without serological markers of hepatitis B.
AB  - To assess the influence of HBV infection on anti-HCV-positive chronic liver
      disease, we performed a prospective case-control study comparing 19 HBsAg
      positive, anti-HCV-positive patients with 38 HBsAg-negative, anti-HCV-positive
      patients, pair-matched for age, sex, and ALT levels. HBV and HCV infections were
      investigated by standard serology and polymerase chain reaction. HCV RNA was
      found in all patients with CAH and in 90.0% with cirrhosis (33% HBsAg-positive).
      HBV DNA sequences were found, in the HBsAg-positive subjects, in 71.4% of CAH and
      in 83.3% of cirrhotics; in the HBsAg-negative ones, only 10% of CAH but 77.7% of
      cirrhotics had demonstrable HBV DNA sequences. Consequently, 80.0% of cirrhotics
      had evidence of both HBV and HCV infection. Conventional serology gives partial
      information on the true occurrence of HBV infection in HBsAg-negative patients,
      while PCR defines more accurately the HBV status. When the rate of double
      infection is defined in this way, it correlates with the presence of cirrhosis.

PMID- 7529675
TI  - Effect of capsaicin on release of substance P-like immunoreactivity from
      vascularly perfused rat duodenum.
AB  - The release of substance P-like immunoreactivity (SPLI) from the rat duodenum was
      investigated using an in situ vascularly perfused preparation. Results show that
      the basal release of SPLI was measurable and significantly enhanced by the
      administration of both 1,3, and 10 microM of capsaicin, indicating that SPLI is
      present in capsaicin-sensitive afferent nerve fibers. It is concluded that the
      present model may be useful for the study of the control of duodenal release of
      SPLI.

PMID- 7529677
TI  - Quantitative RT-PCR assays show Xist RNA levels are low in mouse female adult
      tissue, embryos and embryoid bodies.
AB  - We have investigated expression of the Xist gene in mouse female adult kidney,
      embryos and embryonic stem (ES) cells undergoing in vitro differentiation as
      embryoid bodies. Using the quantitative RT-PCR single nucleotide primer extension
      (SNuPE) assay, we found that the amount of Xist RNA in adult kidney of three
      mouse strains was less than approximately 2000 transcripts per cell, with only
      modest differences between strains carrying different Xce alleles. Female embryos
      7.5 days post coitum had the same number of Xist transcripts per cell as isogenic
      adult tissue. Using quantitative oligonucleotide hybridization assays after RT
      PCR, we investigated Xist expression in ES lines heterozygous at the Pgk-1 and
      Xist loci. We found that, while in most (XX) ES lines Xist RNA levels increased
      during embryoid body formation, the levels seen were less than 10% those found in
      adult female kidney. In addition, we found that the allelic ratio of Xist
      transcripts from reciprocal (XX) ES cell lines differentiating in vitro was
      identical to that of isogenic 10.5 to 11.5 day female embryos. These latter
      results suggest that there is no pattern of preferential paternal imprinting
      during days 1 to 9 of in vitro differentiation of ES cells. However, the
      influence of the Xce locus on the randomness of X-inactivation in embryos seems
      to operate also in ES cell lines. Our overall conclusion is that the low levels
      of Xist RNA in female kidney, embryos and differentiating (XX) ES cells are
      compatible only with models that do not require Xist RNA to cover the entire
      inactive X chromosome.

PMID- 7529679
TI  - Integrin switching regulates normal trophoblast invasion.
AB  - Cells invade extracellular matrices in a regulated manner at specific times and
      places during normal development. A dramatic example is trophoblast invasion of
      the uterine wall. Previous studies have shown that differentiation of
      trophoblasts to an invasive phenotype is accompanied by temporally and spatially
      regulated switching of their integrin repertoire. In the first trimester human
      placenta, alpha 6 integrins are restricted to cytotrophoblast (CTB) stem cells
      and downregulated in invasive CTBs, whereas alpha 5 beta 1 and alpha 1 beta 1
      integrins are upregulated in differentiating and invasive CTBs. The goal of the
      present study was to determine whether these changes have functional consequences
      for CTB invasiveness. Using an in vitro invasion model, we determined first that
      aggregates of invading first trimester CTBs in vitro undergo the same pattern of
      integrin switching as was observed in situ, thereby validating the utility of the
      model. We then showed that antibody perturbation of interactions involving
      laminin or collagen type IV and their integrin alpha 1/beta 1 receptor inhibited
      invasion by CTBs, whereas perturbing interactions between fibronectin and the
      alpha 5/beta 1 fibronectin receptor accelerated invasion. Finally, we report that
      later gestation CTBs, which display greatly decreased invasive capacity, are also
      unable to upregulate alpha 1 beta 1 complexes, providing further evidence that
      this integrin is critical for CTB invasion. This gestational regulation is
      transcriptional. These data indicate that integrin switching observed during
      differentiation in situ has significant functional consequences for CTB invasion.
      The data suggest further that differentiating CTBs upregulate counterbalancing
      invasion-accelerating and invasion-restraining adhesion mechanisms. We propose
      that this contributes to regulating the depth of CTB invasion during normal
      implantation.

PMID- 7529678
TI  - Aprotinin, a Kunitz-type protease inhibitor, stimulates skeletal muscle
      differentiation.
AB  - Aprotinin, a Kunitz-type inhibitor of serine proteases, stimulates myotube
      formation by mouse G8-1 and C2C12 skeletal muscle myoblasts. This stimulation of
      morphological differentiation is accompanied by accumulation of myogenin
      transcripts and production of muscle-specific proteins. In contrast, active TGF
      beta prevents differentiation of G8-1 and C2C12 myoblasts. When active TGF beta
      and aprotinin are both added to myoblast cultures, differentiation is inhibited,
      suggesting the active growth factor acts downstream of the protease inhibitor.
      TGF beta is found in serum as a latent, dimeric propolypeptide that is cleaved by
      limited proteolysis to release the biologically active carboxy-terminal dimer. To
      address the possibility that aprotinin may effect myogenesis by inhibiting
      proteolytic activation of latent TGF beta, levels of the endogenous growth factor
      were measured in differentiating myoblast cultures. Latent TGF beta is rapidly
      depleted from control cultures within 24 hours of plating, but remains relatively
      stable in aprotinin-treated cultures. Consistent with this, aprotinin-treated
      cultures have reduced levels of active TGF beta. These data indicate that Kunitz
      domain containing protease inhibitors may help orchestrate the onset of
      myogenesis, possibly by regulating the activity of TGF beta-like molecules.

PMID- 7529680
TI  - Effects of a single intravenous dose of scopolamine on the quantitative EEG in
      Alzheimer's disease patients and age-matched controls.
AB  - Quantitative EEG (qEEG) was evaluated in Alzheimer's disease (AD) patients and
      age-matched controls following the administration of a single acute intravenous
      dose of scopolamine. Eleven AD patients and 8 cognitively intact age-matched
      controls underwent qEEG in baseline conditions, following double-blind
      intravenous administration of 0.5 mg scopolamine or placebo. At baseline, AD
      patients had significantly decreased absolute and relative alpha and increased
      relative theta amplitudes. In both groups, scopolamine administration was
      followed by a decrease in absolute and relative alpha amplitude, and increase in
      the absolute and relative delta activity. The increase in the absolute and
      relative delta amplitude by scopolamine was significantly more prominent in the
      controls; the decrease of alpha activity, while larger in controls, was not
      statistically different from AD. We conclude that scopolamine affects the change
      in delta amplitude differently in AD patients and controls, probably reflecting
      the reduced cholinergic tone in AD.

PMID- 7529684
TI  - EEG rhythms of the sensorimotor region during hand movements.
AB  - The aim of this study was to determine what motor behaviors or conditions were
      associated with an increased occurrence of beta activity in the sensorimotor
      region of human subjects. EEG recordings were obtained from 8 electrodes
      symmetrically arranged around C3, with 3 cm interelectrode spacing. The electrode
      montage allowed calculation of the Laplacian operator at two positions, C3r and
      C3c, overlying the hand area of the motor cortex and of the somatosensory cortex,
      respectively. A variety of tasks involving right-hand movements of different
      levels of complexity, attention and preparation were performed. The corresponding
      EEG power spectra were subsequently computed for frequencies between 7 and 50 Hz.
      Repetitive hand movements alone (either drawing circles or writing one's
      signature) did not result in significantly increased beta activity in the
      sensorimotor region compared to relaxed conditions. However, both motor
      preparations and focused attention, whether movements were performed or not, were
      associated with an increase of high frequency beta activity (30-50 Hz) in the
      sensorimotor region. Therefore, the facilitatory effect of attention and motor
      preparation and not the functional activation of the sensorimotor cortex by hand
      movements was associated with an increase in synchronized fast beta activity.

PMID- 7529682
TI  - Episodic and semantic memory: an analysis in the EEG theta and alpha band.
AB  - This study examines the hypothesis that in contrast to semantic memory processes
      that are assumed to be reflected primarily within the alpha band, episodic memory
      processes are related to activity within the theta band. EEG signals were
      recorded from subjects as they performed a semantic congruency and an episodic
      recognition task. In the semantic task, subjects had to judge whether or not
      sequentially presented concept-feature pairs (such as "eagle-claws" or "pea
      huge") are semantically congruent. In the episodic task, which followed the
      semantic task without prior warning, the same word pairs were presented together
      with new distractors (generated by repairing known concept-feature pairs). Here,
      subjects judged whether or not a particular concept-feature pair was already
      presented during the semantic task. EEG data were analyzed using event-related
      desynchronization (ERD) as a measure for the amount of event-related changes in
      band power in the theta band and in the upper and lower alpha bands. The alpha
      band was determined individually, using the alpha peak frequency during the
      resting period as the cut-off point to separate the lower from the upper alpha
      band. The results, which are based on those identical word pairs that demanded a
      yes response in both tasks, showed that semantic memory processes are indeed
      primarily reflected in the upper alpha band whereas episodic memory processes are
      reflected in the theta band. The possible relationship between hippocampal theta
      activity and the encoding of episodic information is discussed.

PMID- 7529681
TI  - Analysis of mesial temporal seizure onset and propagation using the directed
      transfer function method.
AB  - The directed transfer function (DTF) method, a multichannel parametric method of
      analysis based on an autoregressive model, is a newly developed tool that permits
      determination of patterns of flow of activity. The DTF method of analysis was
      applied to seizures originating from mesial temporal lobe structures in 3
      patients recorded by combined subdural grid and depth electrode arrays. These
      first applications to human intracranial recordings demonstrated that the DTF
      method can accurately determine patterns of seizure onset and propagation. In
      addition the DTF method can provide evidence regarding patterns of flow of
      seizure activity that are not readily apparent from visual inspection of the EEG
      recordings. Important considerations for appropriate application of the DTF
      method for the analysis of intracranial ictal recordings are discussed.

PMID- 7529688
TI  - A note on the common reference debate.

PMID- 7529683
TI  - Fast wavelet transformation of EEG.
AB  - Wavelet transforms offer certain advantages over Fourier transform techniques for
      the analysis of EEG. Recent work has demonstrated the applicability of wavelets
      for both spike and seizure detection, but the computational demands have been
      excessive. We compare the quality of feature extraction of continuous wavelet
      transforms using standard numerical techniques, with more rapid algorithms
      utilizing both polynomial splines and multiresolution frameworks. We further
      contrast the difference between filtering with and without the use of surrogate
      data to model background noise, demonstrate the preservation of feature
      extraction with critical versus redundant sampling, and perform the analyses with
      wavelets of different shape. Comparison is made with windowed Fourier transforms,
      similarly filtered, at different data window lengths. We here report a dramatic
      reduction in computational time required to perform this analysis, without
      compromising the accuracy of feature extraction. It now appears technically
      feasible to filter and decompose EEG using wavelet transforms in real time with
      ordinary microprocessors.

PMID- 7529687
TI  - Localization of evoked neuromagnetic 600 Hz activity in the cerebral
      somatosensory system.
AB  - Upon electrical median nerve stimulation wide-band scalp SEP recordings show a
      burst of high-frequency low-amplitude wavelets of uncertain origin. Digital high
      pass filtering (above 400 Hz) of the primary cortical response ("N20") can
      separate the burst from the underlying "N20 proper" which itself is known to be
      generated by excitatory postsynaptic potentials (EPSPs) in area 3b. Here,
      neuromagnetic multichannel recordings show a close correlation between the
      spatial field distributions of the magnetic burst and of the magnetic "N20m"
      proper. It is concluded that somatosensory evoked magnetic high-frequency (600
      Hz) wavelets have generators at or near the primary somatosensory cortex.
      Possible modes of generation comprise repetitive discharges conducted in the
      terminal segments of thalamocortical axons and postsynaptic contributions from
      neocortical neurons.

PMID- 7529685
TI  - Somatosensory evoked magnetic fields in patients with stroke.
AB  - We used magnetoencephalography to evaluate areas of sensory cortex in patients
      with ischemic strokes involving the somatomotor system. We measured somatosensory
      evoked magnetic fields using a 7-channel neuromagnetometer and estimated the
      location of cortical responses to median nerve stimulation in 5 patients with
      cortical or subcortical strokes involving the somatomotor system. All patients
      underwent quantitative neurological examinations and a high resolution volumetric
      magnetic resonance imaging. The estimated current dipoles were localized onto the
      patient's own MRI scan in all patients with measurable responses. The location of
      the estimated dipole was always in non-infarcted tissue in the anatomical region
      of the somatosensory cortex. In 1 patient the somatosensory dipole localized to a
      peninsula of cortex flanked by infarcted tissue. Single photon emission computed
      tomography found the localized area of cortex to have significant blood flow. The
      estimated current dipole strengths of somatosensory evoked fields from median
      nerve stimulation correlated significantly (r = 0.95, P < 0.02) with the
      patient's ability to recognize numbers written on the involved palm
      (graphesthesia). The combination of evoked magnetic field recording and magnetic
      resonance imaging is a promising non-invasive technology for studying brain
      function in patients with cerebrovascular disease.

PMID- 7529686
TI  - Analysis of interhemispheric asymmetries of somatosensory evoked magnetic fields
      to right and left median nerve stimulation.
AB  - This paper represents the first neuromagnetic systematic investigation of the
      asymmetries between the sources activated in the right and left hemispheres after
      electric median nerve stimulation. We focused our attention on the location and
      strength of the equivalent sources activated in the primary somatosensory cortex
      contralateral to the stimulated nerve in the 50 msec post-stimulus epoch. The
      spatial coordinates of the equivalent sources did not differ statistically
      significantly in the two hemispheres. Minor individual asymmetries are shown to
      be related to the interhemispheric differences in the position of the central
      sulcus as revealed by MRI investigation. The equivalent sources were
      significantly stronger in the left hemisphere. When comparing the location of the
      generators across individuals, we show that interhemispheric differences
      fluctuate less than absolute values. A quantitative evaluation of these findings
      is also given. Based on these results, a normative data set has been established,
      to be used as a baseline in following up changes of interhemispheric asymmetries
      due to hemispheric lesions and subsequent cortical reorganization.

PMID- 7529689
TI  - Responses in neck and facial muscles to sudden free fall and a startling auditory
      stimulus.
AB  - EMG responses elicited by sudden onset of free fall and a startling auditory
      stimulus were investigated in healthy subjects while lying on a couch with their
      eyes closed. Muscle responses were recorded from masseter (V cranial nerve),
      orbicularis oculi and mentalis (VII nerve) and sternomastoid and trapezoid (XI
      nerve). A similar sequence of muscle activation and absolute latencies occurred
      in response to both stimulus modalities, consisting of a blink (30 msec) followed
      simultaneously by mentalis, sternomastoid and trapezoid (55 msec). Masseter could
      either be simultaneously activated with the latter muscles or follow after a
      delay of 10-20 msec. A patient with bilateral cochleo-vestibular nerve section
      had responses at comparable latencies in the free fall experiment. The
      similarities between the reaction to free fall and a startling auditory stimulus
      indicate that the early response to free fall constitutes a startle and that
      various stimuli converge onto a common response generator. The latency pattern of
      neck and facial muscles does not follow a sequence of innervation with increasing
      segmental distance from a single centre. Therefore, our data do not support the
      concept that the startle response is produced by a caudally and rostrally
      spreading volley from a putative pontomedullary centre. It is suggested that the
      startle response is a polysynaptically generated patterned muscle activation.

PMID- 7529693
TI  - Quantitative EMG in botulinum toxin treatment of cervical dystonia. A double
      blind, placebo-controlled study.
AB  - We used turns-amplitude analysis of the EMG as a guidance for botulinum toxin
      (BT) treatment in 19 patients with cervical dystonia. At the first examination,
      muscles showing abnormal activity (> 100 turns/sec at rest) were given BT 75
      units (10 patients) or placebo (9 patients). At subsequent examinations, about 6,
      12 and 18 weeks after the start, BT 75 units were given to all hyperactive
      muscles. Six weeks after the first BT treatment the sternocleidomastoid muscle
      contralateral to the involuntary head rotation and the ipsilateral and
      contralateral posterior neck muscles (PNM) showed a reduction of involuntary
      activity, as indicated by reduced turns/sec and mean amplitude at rest. Similar
      changes were seen when comparing BT treatment with placebo. The reduction was
      greater in the contralateral sternocleidomastoid muscle than in PNM, suggesting
      that PNM need higher doses of BT. At maximal voluntary contraction, BT treated
      muscles showed unchanged turns/sec (5/6 tests), decreased mean amplitude and
      increased ratio (turns/amplitude). This may reflect a functional random loss of
      muscle fibres, combined with inability to activate all motor units. A high (89%)
      clinical success rate with BT therapy was obtained, and it is concluded that
      quantitative EMG is a useful tool for the precise identification of hyperactive
      muscles, for optimal placing of the injection cannula and for unbiased monitoring
      of the treatment effect.

PMID- 7529694
TI  - Independence of soleus H-reflex tests in control and spastic subjects shown by
      principal components analysis.
AB  - Different soleus H-reflex tests are used in the study of neurophysiological
      mechanisms of motor control. We studied the interdependence pattern of a number
      of soleus H-reflex tests, i.e., vibratory inhibition, the ratio of the reflex
      response to direct muscle potential (H/M ratio) and the homonymous recovery curve
      with a principal components analysis in 48 healthy controls and 38 patients with
      signs of the upper motoneuron syndrome. In controls, the analysis showed 3
      independent principal components (PCs). Vibratory inhibition and H/M ratio loaded
      on separate components. Late facilitation and late inhibition variables of the
      recovery curve loaded on the third component due to the positive correlation (P <
      0.001) between these variables. In spastic patients the analysis identified 4
      independent PCs corresponding with vibratory inhibition, H/M ratio, late
      facilitation and late inhibition variables, respectively. The findings suggest
      that the mutual independence of the different soleus H-reflex tests in patients
      with the upper motoneuron syndrome has retained the control situation to a large
      extent.

PMID- 7529690
TI  - Facilitation and disfacilitation of muscle responses after repetitive
      transcranial cortical stimulation and electrical peripheral nerve stimulation.
AB  - Compound muscle responses were recorded after repetitive electrical stimulation
      of the peripheral nerve and after transcranial electrical and magnetic
      stimulation in 5 healthy persons. The enlargement of the second response at
      intervals between 30 and 50 msec is more pronounced after cortical magnetic and
      electrical stimulation than after peripheral nerve stimulation. This difference
      is believed to be a result of facilitatory mechanisms involving the summation of
      effects from conditioning and test stimuli along the entire central motor
      pathway. The facilitation at 10 msec interval, which is only seen after magnetic,
      but not after electrical transcranial stimulation could indicate an intracortical
      mechanism.

PMID- 7529692
TI  - Effects of diphenylhydantoin on motor potentials evoked with magnetic
      stimulation.
AB  - We studied the effect of an acute loading dose of diphenylhydantoin (DPH) on
      motor responses elicited with cortical magnetic stimulation in normal subjects.
      DPH increased significantly the motor threshold activation of ADM, APB, FDI and
      biceps. The motor threshold increase was of greater magnitude for the proximal
      muscle. Spinal soleus alpha-motoneuron pool excitability assessed by H-reflex was
      increased significantly suggesting that the motor threshold increase is related
      to a supraspinal effect of the drug. Our study demonstrates that the motor
      threshold increase observed after DPH administration occurs not only in epileptic
      patients but also in normal subjects.

PMID- 7529691
TI  - Responses of the soleus muscle to transcranial magnetic stimulation.
AB  - Soleus muscle responses are difficult to elicit by cortical stimulation in normal
      humans at rest. We have studied in normal volunteers the behavior of the soleus
      and tibialis anterior muscle responses to maximal intensity transcranial magnetic
      stimulation (TMS) in the following experimental conditions: lying in supine
      position, active ankle dorsal flexion, active plantar flexion, standing on the
      soles, standing on the toes, and standing on the heels. At rest, consistent
      responses were recorded in the soleus to 61% of the stimuli, only. Maximal
      facilitation of the response in the soleus occurred when standing on the toes. In
      this condition, responses were recorded to 100% of the stimuli, at a latency that
      was, on average, 5.2 msec shorter than the latency of the responses at rest, and
      similar to the latency of the responses recorded in the tibialis anterior muscle
      when standing on the heels. Central motor conduction time, calculated in
      conditions of maximal facilitation, was not different for soleus or tibialis
      anterior muscles. We conclude that the soleus muscle receives short latency
      excitatory inputs from cortico-spinal axons activated by TMS, with a conduction
      time similar to that for the tibialis anterior. Such short latency cortico-spinal
      connections to the soleus muscle may become functionally effective only during
      maximum enhancement of motoneuronal excitability by muscle contraction.

PMID- 7529695
TI  - Conduction abnormalities detected by silent period testing.
AB  - Cutaneous and mixed nerve silent periods (SPs) were analyzed in 2 patients with
      pure sensory neuropathy and in 5 healthy controls. In patients, sensory nerve
      action potentials (SNAPs) and somatosensory evoked potentials (SEPs) were absent,
      but digital and mixed nerve stimulation evoked complete SPs in voluntarily
      contracting thenar muscles. Marked differences in SP latencies were found between
      the patients, despite shared diagnoses and virtually identical nerve conduction
      studies. When compared with controls, SPs were normal in the first patient and
      markedly delayed in the second. Such findings suggest that SPs can identify
      conduction abnormalities not detected by routine studies. The pathologic
      correlate to these abnormalities remains uncertain, although electrophysiologic
      data suggest that the smaller, slower conducting delta fibers carry the impulses
      that generate these SPs.

PMID- 7529696
TI  - The problem of bimanual coupling: a reaction time study of simple unimanual and
      bimanual finger responses.
AB  - The properties of the sensorimotor system controlling finger movements were
      investigated in the simple uni- and bimanual reaction time (RT) paradigm, with
      emphasis on the problem of interhemispheric transfer of sensory and motor
      information. Unimanual and bimanual responses of the index fingers were elicited
      by stimulation of either left or right hand and resulting reaction times were
      compared to assess the degree of right-left differences and thus also of crossed
      uncrossed differences (CUD). The response consisted of a force pulse (first
      dorsal interosseus muscle) which was elicited by a non-painful electrical
      stimulus applied to the base of the middle finger. In unimanual experiments, the
      population analysis showed that RTs obtained with contralateral stimuli were
      significantly longer (6 msec) than RTs elicited with ipsilateral stimuli.
      However, inter-subject differences were large and sometimes pointed in the non
      expected direction (crossed < uncrossed). Statistically significant right-left
      differences in RT were detected in the bimanual response paradigm, but these
      differences occurred in both directions with the crossed RT either longer or
      shorter than uncrossed RT. The analysis of the correlation structure of bimanual
      RT suggested the presence of stimulus-related asymmetries of the hands. These
      observations provide some support for the notion of an additional processing time
      related to interhemispheric transmission of sensory and/or motor signals. In
      addition, it turned out that factors other than callosal transmission can also
      produce asymmetries in RTs of the two hands. Thus some subjects had consistent
      right-left differences which were unrelated to callosal transmission. Asymmetries
      were also introduced by changing the stimulation side. In the light of this multi
      factorial influence, we argue that the underlying mechanisms leading to
      intermanual asymmetries in RT cannot be attributed exclusively to callosal
      transmission.

PMID- 7529697
TI  - Visualization of a moving quadrupole with magnetic measurements of peripheral
      nerve action fields.
AB  - Magnetic compound action fields (CAFs) over the right arm were measured from 63
      sensor positions with two 7-channel SQUID gradiometer systems following
      electrical stimulation of the median nerve at the wrist. The field mapping of the
      CAFs revealed a propagating quadrupolar pattern with the leading depolarization
      and trailing repolarization fronts. The average distribution of the CAFs in the
      longitudinal direction was 9.0 cm in length for the depolarization field and 7.3
      cm for the repolarization field in good agreement with a theoretical prediction
      based on the duration (3 msec) of the CAFs and the conduction velocity of the
      nerve (50 m/sec). The distance between the maxima of the depolarization front and
      the minima of the repolarization front was 6.3 cm. This spatial separation of the
      leading and trailing dipole locations suggests in part mutual cancellation of the
      fields with opposite polarity at or near the depolarized segment of nerve fibers.

PMID- 7529699
TI  - Exhaust emissions from light- and heavy-duty vehicles: chemical composition,
      impact of exhaust after treatment, and fuel parameters.
AB  - This paper presents results from the characterization of vehicle exhaust that
      were obtained primarily within the Swedish Urban Air Project, "Tatortsprojektet."
      Exhaust emissions from both gasoline- and diesel-fueled vehicles have been
      investigated with respect to regulated pollutants (carbon monoxide [CO],
      hydrocarbon [HC], nitrogen oxides [NOx], and particulate), unregulated
      pollutants, and in bioassay tests (Ames test, TCDD receptor affinity tests).
      Unregulated pollutants present in both the particle- and the semi-volatile phases
      were characterized. Special interest was focused on the impact of fuel
      composition on heavy-duty diesel vehicle emissions. It was confirmed that there
      exists a quantifiable relationship between diesel-fuel variables of the fuel
      blends, the chemical composition of the emissions, and their biological effects.
      According to the results from the multivariate analysis, the most important fuel
      parameters are: polycyclic aromatic hydrocarbons (PAH) content, 90% distillation
      point, final boiling point, specific heat, aromatic content, density, and sulfur
      content.

PMID- 7529700
TI  - Monitoring of human populations at risk by different cytogenetic end points.
AB  - Humans are exposed to a large number of environmental genotoxic agents. These can
      increase the probability that somatic mutation will occur. The use of
      genotoxicity testing is essential for assessment of potential human toxicity so
      that hazards can be prevented. Cytogenetic monitoring of human populations
      exposed to chemicals has proved to be a useful tool for detecting the chemical
      mutagenic effects. Cytogenetic analysis of human chromosomes in peripheral
      lymphocytes allows direct detection of mutation in somatic cells. Cytogenetic
      monitoring of a group of traffic policemen from Cairo, Egypt, was an example of a
      human population study. The induction of chromosomal damage was studied in a
      group of 28 traffic policemen with exposure of over 10 years and a control group
      of 15 policemen trainers. Blood lead level was significantly higher in the
      traffic policemen (30 +/- 8.7) unit compared to the control group (18.2 +/- 1.2)
      unit. The percentage of chromosomal aberrations (7.7 +/- 3.1), as well as the
      mean sister chromatid exchanges (7.5 +/- 3.4), were significantly higher among
      the traffic policemen than in the control group. The percentage of chromosomal
      aberrations was 2.8 +/- 2.1 and the mean sister chromatid exchanges was 4.8 +/-
      2.9 in the control group. On the other hand, the increase in chromosome damage
      among the traffic policemen was enhanced further by smoking. Several problems
      that are found in biomonitoring studies are discussed.

PMID- 7529698
TI  - Dioxin-receptor ligands in urban air and vehicle exhaust.
AB  - The ability of extracts of urban air and vehicle exhaust particulates to bind to
      the dioxin receptor has been determined. It was shown that such extracts do
      contain significant amounts of dioxin-receptor binding activity. The level of
      dioxin-receptor binding found in ambient air reflects its pollution level as
      determined by mutagenic activity. Furthermore, it was shown that the extracts of
      both urban air and vehicle exhaust particulates could provoke the induction of
      cytochrome P450IA1 in cultured rat hepatoma cells. Chemical fractionation of the
      extracts revealed that the majority of the dioxin-receptor binding activity from
      urban air and gasoline vehicle samples fractionated with the polycyclic aromatic
      compounds. However, unknown polycyclic aromatic compounds were responsible for
      the majority of the binding activity measured. In the case of diesel vehicle
      exhausts, the majority of the dioxin-receptor binding activity was found to be
      associated with nitro-polycyclic aromatic compounds. Studies with a variety of
      diesel fuels showed that the amount of dioxin-receptor ligands present in exhaust
      emissions are fuel-dependent and that substantial amounts of dioxin-receptor
      ligands are present in the semivolatile phase of exhaust emissions.

PMID- 7529702
TI  - Cancer risk of air pollution: epidemiological evidence.
AB  - Epidemiological studies on the effect of urban air pollution on lung cancer were
      surveyed. Overall, the studies from many countries point to a smoking-adjusted
      risk in urban areas over countryside areas that is higher by a factor of up to
      1.5. The extent to which urban air pollution contributes to this excess remains
      unknown. Studies on diesel-exposed occupational groups show that urban air
      pollution may have a causative role in lung cancer. Model calculations on unit
      risk factors of known human carcinogens were carried out to rank carcinogens
      according to their current ambient air concentrations.

PMID- 7529703
TI  - Future research needs associated with the assessment of potential human health
      risks from exposure to toxic ambient air pollutants.
AB  - This paper presents key conclusions and future research needs from a Workshop on
      the Risk Assessment of Urban Air, Emissions, Exposure, Risk Identification, and
      Quantification, which was held in Stockholm during June 1992 by 41 participants
      from 13 countries. Research is recommended in the areas of identification and
      quantification of toxics in source emissions and ambient air, atmospheric
      transport and chemistry, exposure level assessment, the development of improved
      in vitro bioassays, biomarker development, the development of more accurate
      epidemiological methodologies, and risk quantification techniques. Studies are
      described that will be necessary to assess and reduce the level of uncertainties
      associated with each step of the risk assessment process. International
      collaborative research efforts between industry and government organizations are
      recommended as the most effective way to carry out this research.

PMID- 7529701
TI  - Toxicological and epidemiological evidence for health risks from inhaled engine
      emissions.
AB  - Information from toxicological and epidemiological studies of the cancer and
      noncancer health risks from inhaled diesel engine exhaust (DE) and gasoline
      engine exhaust (GE) was reviewed. The toxicological database is more extensive
      for DE than for GE. Animal studies have shown that heavy, chronic exposures to
      both DE and GE can cause lung pathology and associated physiological effects.
      Inhaled GE has not been shown to be carcinogenic in animals. Chronically inhaled
      DE at high concentrations is a pulmonary carcinogen in rats, but the response is
      questionable in mice and negative in Syrian hamsters. The response in rats is
      probably not attributable to the DE soot-associated organic compounds, as
      previously assumed, and the usefulness of the rat data for predicting risk in
      humans is uncertain. Experimental human exposures to DE show that lung
      inflammatory and other cellular effects can occur after single exposures, and
      sparse data suggest that occupational exposures might affect respiratory function
      and symptoms. Epidemiology suggests that heavy occupational exposures to exhaust
      probably increase the risks for mortality from both lung cancer and noncancer
      pulmonary disease. The small magnitudes of the increases in these risks make the
      studies very sensitive to confounding factors and uncertainties of exposure;
      thus, it may not be possible to resolve exposure-response relationships
      conclusively by epidemiology. Our present knowledge suggests that heavy
      occupational exposures to DE and GE are hazardous but does not allow quantitative
      estimates of risk with a high degree of certainty.

PMID- 7529704
TI  - A perspective on the potential development of environmentally acceptable light
      duty diesel vehicles.
AB  - Between 1979 and 1985, an international technical focus was placed upon potential
      human health effects associated with exposure to diesel emissions. A substantial
      data base was developed on the composition of diesel emissions; the fate of these
      emissions in the atmosphere; and the effects of whole particles and their
      chemical constituents on microorganisms, cells, and animals. Since that time, a
      number of significant developments have been made in diesel engine technology
      that require a new look at the future acceptability of introducing significant
      numbers of light-duty diesel automobiles into the European and American markets.
      Significant engineering improvements have been made in engine design, catalysts,
      and traps. As a result, particle emissions and particle associated organic
      emissions have been reduced by about 10 and 30 times, respectively, during the
      past 10 years. Research studies to help assess the environmental acceptability of
      these fuel-efficient engines include the development of an emissions data base
      for current and advanced diesel engines, the effect of diesel emissions on urban
      ozone formation and atmospheric particle concentrations, the effect of fuel
      composition, e.g., lower sulfur and additives on emissions, animal inhalation
      toxicology studies, and fundamental molecular biology studies.

PMID- 7529705
TI  - The relationship between gasoline composition and vehicle hydrocarbon emissions:
      a review of current studies and future research needs.
AB  - The purpose of this paper is to review current studies concerning the
      relationship of fuel composition to vehicle engine-out and tail-pipe emissions
      and to outline future research needed in this area. A number of recent combustion
      experiments and vehicle studies demonstrated that reformulated gasoline can
      reduce vehicle engine-out, tail-pipe, running-loss, and evaporative emissions.
      Some of these studies were extended to understand the fundamental relationships
      between fuel composition and emissions. To further establish these relationships,
      it was necessary to develop advanced analytical methods for the qualitative and
      quantitative analysis of hydrocarbons in fuels and vehicle emissions. The
      development of real-time techniques such as Fourier transform infrared
      spectroscopy, laser diode spectroscopy, and atmospheric pressure ionization mass
      spectrometry were useful in studying the transient behavior of exhaust emissions
      under various engine operating conditions. Laboratory studies using specific
      fuels and fuel blends were carried out using pulse flame combustors, single- and
      multicylinder engines, and vehicle fleets. Chemometric statistical methods were
      used to analyze the large volumes of emissions data generated from these studies.
      Models were developed that were able to accurately predict tail-pipe emissions
      from fuel chemical and physical compositional data. Some of the primary fuel
      precursors for benzene, 1,3-butadiene, formaldehyde, acetaldehyde and C2-C4
      alkene emissions are described. These studies demonstrated that there is a strong
      relationship between gasoline composition and tail-pipe emissions.

PMID- 7529706
TI  - Air pollution measurements in traffic tunnels.
AB  - Air pollution measurements during April 1991 are reported from the Craeybeckx
      highway tunnel in Antwerp, Belgium. The tunnel was used daily by an average of
      45,000 vehicles, of which 60% were gasoline fueled passenger cars, 20% diesel
      cars, and 20% trucks. Of the gasoline cars, only 3% had three-way catalysts.
      Tunnel air concentrations of nitrogen oxides, sulphur dioxide, carbon dioxide,
      carbon monoxide, nonmethane hydrocarbons, volatile organic compounds, polycyclic
      aromatic hydrocarbons, and lead are presented. The traffic emissions in the
      tunnel are calculated by the carbon balance method, which uses the increase of
      the total carbon concentration in the tunnel air as the reference quantity.
      Division of the concentration of any pollutant by the total carbon concentration
      gives emission factors per kilogram of carbon. These emission factors can be
      converted directly to emissions relative to fuel consumption or per kilometer.
      The fraction of diesel used in the tunnel was derived from sulphur to carbon
      ratios in tunnel air. A calculation procedure with breakdown of emission factors
      according to vehicle categories was used to estimate countrywide emissions. The
      estimated emissions were compared to results from the Flanders Emissions
      Inventory [Emissie Inventaris Vlaamse Regio (EIVR)] and calculated emissions
      according to the emission factors proposed by the European Commissions CORINAIR
      Working Group. For NOx there is excellent agreement. For carbon monoxide and
      hydrocarbons, the tunnel data produced higher emissions than the CORINAIR model
      would predict but lower than the official EIVR statistics. The estimated lead
      emissions from traffic are found to be 22 to 29% of the lead in gasoline.

PMID- 7529707
TI  - Exposure and risk from ambient particle-bound pollution in an airshed dominated
      by residential wood combustion and mobile sources.
AB  - A major field study was conducted in Boise, Idaho, during the heating season of
      1986 to 1987 as part of the Integrated Air Cancer Project. Filter samples were
      systematically collected in residences and in the ambient air across the
      community to characterize the particle-bound pollutants. The extractable organic
      matter (EOM) from the filter samples was apportioned to its source of origin,
      either residential wood combustion (RWC) or mobile sources (MS). Two composite
      samples, with apportioned contributions from RWC and MS, were prepared from the
      Boise ambient samples and tested for tumor-initiation potency. A comparative
      potency lung cancer risk estimate has been made based on the two ambient
      composite samples from this airshed. In addition, a microenvironmental exposure
      model was developed from the Boise data and from national survey data to estimate
      the exposure to EOM from RWC and MS. In this paper, the microenvironmental model
      is extrapolated to provide an estimate of the average annual exposure and dose in
      Boise to EOM from RWC and MS. The annual model considers actual pollutant levels
      in Boise, historical changes in RWC usage and meteorological dilution factors and
      the likely activities in the various microenvironmental zones and their resultant
      inhalation rates. Combined with the lifetime risk estimates, the average annual
      dose suggests a risk of about 4 x 10(-4) based upon the composite ambient
      samples. Despite the fact that RWC accounts for 73% of the EOM on an annual
      average basis, it accounts for only about 20% of the estimated lifetime risk.

PMID- 7529709
TI  - Atmospheric pollution due to mobile sources and effects on human health in Japan.
AB  - Following the rapid economic growth after World War II, diseases associated with
      environmental pollution frequently occurred due to delayed implementation of
      countermeasures against environmental pollution. These diseases are exemplified
      by Minamata disease, Itai-itai disease, chronic arsenic poisoning, and Yokkaichi
      asthma. After multiple episodes of these pollution-related diseases were
      experienced, the government and the private sector made joint efforts to reduce
      environmental pollution. As a result of these efforts and because of changes in
      the industrial structure, pollution-related diseases have declined. Instead,
      however, air pollution from automobile exhaust and the health effects of
      automobile exhaust on people living along roads with heavy traffic began to
      attract the public's attention after an increase in the use of automobiles. The
      epidemiological surveys carried out by the Environmental Agency and the Tokyo
      Metropolitan Government also have suggested unfavorable effects of automobile
      caused air pollution on people living in large cities or along major roads. To
      solve this problem, it seems imperative to promote the reasonable use of
      automobiles and to work toward more efficient transportation of goods based on
      analyses of city structure, the life-styles of city dwellers, and the
      socioeconomic composition of cities. In addition, the discharge of pollutants
      from automobiles could be controlled.

PMID- 7529708
TI  - Chemical analysis and biological testing of a polar fraction of ambient air,
      diesel engine, and gasoline engine particulate extracts.
AB  - Extracts of gasoline and diesel vehicle exhaust and ambient air particles were
      fractionated into five fractions according to polarity on a silica gel column.
      Two medium polar fractions showing high genotoxic activity in the Ames test were
      further subfractionated, using normal-phase high-performance liquid
      chromatography. Chemical analyses were performed by means of gas chromatography
      combined with mass spectrometry and flame ionization and detection. The crude
      extracts, fractions, and subfractions were assayed with the Ames test, with and
      without S9, and the most abundant compounds in the subfractions are reported.

PMID- 7529710
TI  - Vasodilating actions of cromakalim in resting and contracting states of carotid
      arteries from spontaneously hypertensive rats.
AB  - To determine the properties of cromakalim-opened K+ channels in arterial smooth
      muscle of spontaneously hypertensive rats (SHR), the effects of cromakalim on
      tension and 86Rb efflux were compared in endothelium-denuded strips of carotid
      arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). The
      addition of cromakalim or of nifedipine to resting strips caused a relaxation
      only in SHR. When strips from both strains were contracted with 15.9 mM K+, the
      magnitude of the precontraction was greater in SHR than in WKY. Under these
      conditions, relaxant responses to lower concentrations of cromakalim were
      decreased and those to higher concentrations of cromakalim were increased in SHR.
      When strips from both strains were contracted with a different concentration of
      K+ to an equivalent magnitude (78% of the maximum) relaxant responses to
      cromakalim were greater in SHR than in WKY. When strips were contracted with 10(
      7) M norepinephrine, the precontraction was similar between SHR and WKY, and
      relaxant responses to cromakalim were greater in SHR. In both strains, the
      relaxant responses to cromakalim were competitively antagonized by glibenclamide,
      a blocker of ATP-sensitive K+ (KATP) channels, with a pA2 value of approximately
      7.3. Charybdotoxin (10(-7) M), a blocker of Ca(2+)-activated K+ (KCa) channels,
      did not inhibit the relaxant responses to cromakalim in both strains.
      Charybdotoxin alone elicited a contraction, which was greater in SHR than in WKY.
      In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was
      higher in SHR than in WKY. The addition of cromakalim (10(-5) M) to the resting
      strips increased the 86Rb efflux rate constant in both strains to a similar peak
      value. The addition of nifedipine (10(-7) M) to the resting strips decreased the
      basal 86Rb efflux rate constant only in SHR, and concomitantly affected the
      action of cromakalim in SHR. The results suggest that (1) cromakalim caused
      arterial relaxation via the opening of KATP channels in both SHR and WKY, (2)
      although the relaxant effects of cromakalim tended to be greater in SHR than in
      WKY, the differences were rather small, depended on the precontraction tone and
      varied with the concentration of the vasoconstrictors, and (3) there was an
      increased basal Ca2+ influx and a high activation of KCa channels in the resting
      state of SHR arteries, and these changes might influence the effects of
      cromakalim.

PMID- 7529711
TI  - Clomipramine and clonazepam increase cholecystokinin levels in rat ventral
      tegmental area and limbic regions.
AB  - Recent reports suggest that a cholecystokinin (CCK)-related dysfunction may be a
      target by which drugs can modulate anxiety and panic disorders. In the present
      study, effects of subchronic (14 days) treatment with the monoamine uptake
      inhibitors nortriptyline (30 mumol/kg per day), amitriptyline (29 mumol/kg per
      day), clomipramine (32 mumol/kg per day) and alaproclate (39 mumol/kg per day),
      as well as with the benzodiazepine clonazepam (0.25 mumol/kg per day), on rat
      brain levels of CCK- and substance P-like immunoreactivity, were compared. The
      drugs were administered by continuous s.c. infusion using implanted osmotic
      pumps. The plasma concentrations of the monoamine uptake inhibitors were similar
      after 1 and 2 weeks of treatment, indicating that steady-state plasma levels had
      been reached during the first week. Treatment with clomipramine or clonazepam
      increased the CCK-like immunoreactivity level in the ventral tegmental area (by
      64.4 +/- 28.8% and 105.1 +/- 28.8%, respectively) and in the cingulate cortex (by
      30.3 +/- 10.1% and 36.0 +/- 11.8%, respectively) (P < 0.05 or P < 0.01).
      Clomipramine also significantly increased the CCK-like immunoreactivity level in
      the periaqueductal grey by 85.1 +/- 29.7%. Neither nortriptyline nor
      amitriptyline or alaproclate produced any significant alterations in the CCK- or
      substance P-like immunoreactivity levels in the areas examined. The present
      results may suggest that an altered utilization of CCK in limbic circuits could
      be of importance for the well documented clinical effect of clomipramine and
      clonazepam in panic disorders.

PMID- 7529712
TI  - Pathways involved in muscarinic M1 and M2 receptor stimulation in rabbit vas
      deferens.
AB  - Pretreatment of the field-stimulated rabbit isolated vas deferens for 30 min with
      LiCl (2 x 10(-2) and 4 x 10(-2) M) attenuated the inhibition of neurogenic twitch
      contractions due to muscarinic M1 receptor stimulation by 4-(4
      chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium iodide (4-Cl-McN-A-343), and
      enhanced the muscarinic M2 receptor-mediated potentiation of contractions evoked
      by carbachol. When the tissues were preincubated for 5 min with the adenylate
      cyclase activator, forskolin (3 x 10(-8)-3 x 10(-7) M), the response to carbachol
      was attenuated whereas that to 4-Cl-McN-A-343 remained unchanged. 1,9-Dideoxy
      forskolin (3 x 10(-7) and 10(-6) M), which fails to activate cyclase, did not
      abolish the carbachol effect. In addition, desensitization of the response to 4
      Cl-McN-A-343 but not to carbachol occurred in preparations incubated for 90 min
      with the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA, 3 x
      10(-8)-3 x 10(-7) M), whereas its inactive 4 alpha-stereoisomer (4 alpha-PMA, 3 x
      10(-7) M) was without effect. In unstimulated preparations, LiCl, forskolin and
      PMA did not impair contractions due to exogenous ATP (10(-3) M). These findings
      are consistent with the hypothesis that, in rabbit vas deferens, inhibitory
      muscarinic M1 receptors stimulate LiCl-sensitive phosphatidylinositol turnover
      (IP3 pathway) involving protein kinase C, whilst excitatory muscarinic M2
      receptors are coupled to inhibition of adenylate cyclase, resulting in reduced
      levels of cyclic AMP.

PMID- 7529713
TI  - Progressive changes in striatal dopaminergic markers, nigral volume, and
      rotational behavior following iron infusion into the rat substantia nigra.
AB  - Excess iron (Fe) within the substantia nigra zona compacta (SNc) has been
      implicated in the pathogenesis of Parkinson's disease (PD). We recently reported
      that intranigral Fe infusion into the rat substantia nigra (SN) induces dose
      dependent SN neurodegeneration and associated reductions in striatal dopaminergic
      (DA) markers. The objective of the present study was to determine whether infused
      Fe is capable of inducing persistent/progressive neurodegenerative changes
      relevant to PD. Following unilateral infusions of vehicle, 1.25 or 2.10 nmol Fe
      into the rat SN, SNc neuronal loss, SN volume, striatal neurochemical markers,
      and apomorphine-induced rotational behavior were assessed at 2, 4, and 6 months.
      Semiquantitative analysis of thionine-stained SNc neurons demonstrated an initial
      modest neuronal loss which remained stable through 6 months postinfusion. Fe
      induced SN atrophy was dose-dependent and progressive through 6 months. Striatal
      DA and homovanillic acid levels were progressively decreased at least through 4
      months following 1.25 nmol Fe infusion; both doses of Fe induced significant
      reductions of both DA markers at 4 months with no recovery evident through 6
      months. Apomorphine-induced rotational behavior progressively increased for both
      Fe infusion groups through the 6 months of testing. These data indicate that a
      single exposure of the SN to a modest amount of Fe can induce
      persistent/progressive changes occurring through a number of months postinfusion
      and further establishes intranigral Fe infusion as an animal model for PD.

PMID- 7529714
TI  - Effect of amitriptyline on the analgesia induced by adrenal medullary tissue
      transplanted in the rat spinal subarachnoid space as measured by an experimental
      model of acute pain.
AB  - The effect of short and long term amitriptyline (AMI) treatment on the analgesia
      induced by adrenal medullary autotransplant into the subarachnoid space was
      investigated in rats. For this purpose, two experiments were carried out. In the
      first one, the rats were chronically treated for 28 days after transplantation.
      In the second experiment, rats were treated for 28 days starting 28 days after
      surgery. Before starting the experiments, basal levels were tested. Tail-flick
      latencies were checked at Day 4 and Day 28 in the first experiment and at Day 28
      and Day 56 in the second. AMI itself did not induce any tail-flick modification
      after 28 or 56 days. However, it increased the transplantation-induced analgesia
      at Day 28 in the first experiment and at Day 56 in the second. These results are
      interpreted in the sense of the ability of AMI to enhance the effects of both
      monoamine and opioids previously released by the transplantation.

PMID- 7529715
TI  - Ss40: the zinc endopeptidase secreted by infective larvae of Strongyloides
      stercoralis.
AB  - Infective larvae of a pathogenic nematode of humans, Strongyloides stercoralis,
      release a potent zinc endopeptidase activity which has a broad substrate
      specificity for constituents of extracellular dermal matrix, including elastin.
      Specific inhibitors of zinc endopeptidases prevent the penetration of mammalian
      skin by S. stercoralis larvae. We now report the molecular size and isoelectric
      point of the S. stercoralis zinc endopeptidase at 40 kDa, pI 5 by zymogram
      analysis. The activity was not influenced by incubation with beta-mercaptoethanol
      at 22 degrees C, but was inactivated by incubation at 100 degrees C for 2 min.
      The enzyme, which we term Ss40, is immunogenic and stimulates humoral IgG
      antibodies during infection of humans; the activity was immunoprecipitable from
      ES with pooled infection sera. In addition, a HPLC-enriched Ss40 preparation
      stimulated the release of histamine from peripheral blood leukocytes of S.
      stercoralis-infected persons, suggesting that Ss40 is allergenic in humans.

PMID- 7529717
TI  - Plasmodium falciparum: a comparison of the activity of Pfs230-specific antibodies
      in an assay of transmission-blocking immunity and specific competition ELISAs.
AB  - The activity of monoclonal antibodies (mAbs) that specifically recognize the
      Plasmodium falciparum sexual stage-specific protein Pfs230 was analyzed. All mAbs
      reacted with the surface of extracellular sexual forms of the parasite in a
      suspension immunofluorescence antibody reaction and precipitated the Pfs230
      protein from an NP-40 extract of surface radioiodinated macrogametes/zygotes.
      Only mAb that bound complement blocked transmission, whereas mAb that did not
      bind complement but competed with the complement-binding mAb for binding to the
      same epitope did not block transmission. These mAbs were used to develop Pfs230
      specific competition ELISAs to analyze epitope diversity and to analyze the
      binding characteristics of anti-Pfs230 antibodies in human serum. Transmission
      blocking (TB) antibodies in test/field sera competed in the competition ELISA for
      binding with epitope-specific, labeled mAbs against Pfs230. At least five
      different epitope regions could be defined with the competition ELISAs. All 46
      sera from gametocyte carriers immunoprecipitated the Pfs230 molecule, while 19 of
      these sera blocked transmission in the bioassay. Five of the transmission
      blocking and one of the nonblocking sera competed with monoclonal antibodies. A
      method comparison analysis was used to determine agreement between reactions in a
      competitive ELISA and the TB activity examined in the bioassay. The index of
      agreement kappa between outcomes of the bioassay and ELISA was fair to poor
      (kappa = 0.25) but since its range includes values below 0 the relation between
      the data obtained by the bioassay and the competition ELISA can be explained by
      chance alone. The serological data did not reveal a correlation between
      immunoprecipitation of Pfs230 and TB activity.

PMID- 7529716
TI  - Plasmodium falciparum: characterization of adhesion of flowing parasitized red
      blood cells to platelets.
AB  - Adhesion of parasitized red blood cells to vascular endothelium contributes to
      the ischaemic pathology of severe falciparum malaria. One of the endothelial
      cytoadhesion receptors, CD36, is also expressed by platelets. We have studied
      adhesion of flowing parasitized cells to a surface coated with immobilized,
      activated platelets, both as a model for CD36-mediated adhesion and because
      interaction with platelets might play a direct role in thrombotic complications
      of malaria. Parasitized cells were able to bind firmly to platelets over a range
      of shear stress (up to 0.3 Pa) close to those found in the microcirculation. The
      binding was largely abolished by treatment of platelets with antibody to CD36,
      with only a small effect by antibody to ICAM-1. Binding showed pH sensitivity
      consistent with previous reports of CD36-mediated cytoadhesion. Fixation of the
      platelet surface with formaldehyde preserved adhesion and its antibody
      sensitivity, while fixation with glutaraldehyde greatly reduced adhesion and
      increased the sensitivity to antibody against ICAM-1. Thus CD36-mediated binding
      is inhibited by glutaraldehyde--but not formaldehyde--fixation, while ICAM-1 can
      mediate adhesion after either form of fixation. We conclude that platelet-coated
      surfaces (with or without fixation) represent a practically simple model for
      studying malarial cytoadhesion and that platelets are likely to be able to bind
      parasitized cells in vivo and could thus promote vascular occlusion.

PMID- 7529719
TI  - A Xenopus homologue of the NGFI-B orphan receptor.

PMID- 7529722
TI  - Gastric mucosal nitric oxide synthase activity: inhibition by phosphorylation,
      arginine analogues and trifluoperazine.

PMID- 7529721
TI  - Nitric oxide synthase activity in collagenase digests of rat small intestinal
      muscle can be resolved from the muscle cells on a Percoll gradient.

PMID- 7529720
TI  - Molecular characterisation of the Na+/glucose co-transporter from the sheep
      parotid gland acinar cell.

PMID- 7529723
TI  - Studies of the bacterial endosymbionts of "anaerobic protozoa" using
      fluorescently-labelled rRNA-targetted oligonucleotide probes.

PMID- 7529718
TI  - Increased protein tyrosine-phosphorylation in primary T-cells transduced with
      Tax1 of human T-cell leukemia virus type I.
AB  - Protein tyrosine-phosphorylation in primary human T-cells transduced with Tax1 of
      Human T-cell leukemia virus type I was investigated. In comparison with control T
      cells, the level of protein tyrosine-phosphorylation after stimulation with anti
      CD3 antibody increased significantly in Tax1-transduced T-cells. This enhancement
      in tyrosine-phosphorylation possibly accounted for the augmented proliferation
      response of these cells, which has been reported previously [J. Virol. 67 (1993)
      1211-1217].

PMID- 7529724
TI  - Protein expression and development of oxidase "priming" in maturing HL60 cells.

PMID- 7529727
TI  - Adrenal dysfunction: effects on small intestinal protein synthesis in vivo.

PMID- 7529726
TI  - Thyroidectomy induces biochemical changes in the rat heart: the contribution of
      anorexia.

PMID- 7529725
TI  - Identification of lipopolysaccharide binding protein-like activity in bovine
      serum.

PMID- 7529728
TI  - Synthesis and antiviral properties of sterol phosphonoformates.

PMID- 7529729
TI  - The M2 transmembrane segment as a molecular determinant of the ion permeation
      properties in the superfamily of ligand-gated ion channels.

PMID- 7529730
TI  - APO-I-mediated apoptosis in normal and malignant lymphocytes.

PMID- 7529731
TI  - Activation of the human IGFBP-1 gene promoter by progestin and relaxin in primary
      culture of human endometrial stromal cells.
AB  - We have studied the activity for the insulin-like growth factor binding protein-1
      (IGFBP-1) gene promoter in human endometrial stromal cells by transient
      transfection. The promoter activity derived from p3.6CAT or p3.6Luc (3400 bp
      IGFBP-1 promoter 5' to the reporter gene chloramphenicol acetyltransferase or
      luciferase) was minimal in unstimulated cells. A time study over 13 days of
      culture showed that the promoter activity increased exponentially to > 10(4) fold
      in cells treated with medroxyprogesterone acetate (MPA) and relaxin (RLX).
      Induction of the IGFBP-1 gene promoter activity by hormones was similar to the
      secretion pattern of IGFBP-1 in endometrial stromal cells. MPA alone caused a
      moderate induction, 3-40-fold increase over the control. Deletion analysis showed
      that two regions in the IGFBP-1 gene promoter were responsible for the activation
      of the IGFBP-1 gene. The basal promoter region, termed bp1-A (+68 bp to -1.205
      kb), contains multiple sections of regulatory sequence including a cis-element
      CCAAT (-72 bp). A DNase I protection assay in the bp-1A region revealed four
      distinct binding regions, one of which contained the CCAAT box region. Another
      promoter region, termed bp1-B (-2.6 to -3.4 kb), mediated 95% of the total
      promoter activity in endometrial stromal cells. The bp1-B region also contains
      multiple regulatory sequences. Mutation and DNase I protection assay suggest that
      Sp1-like binding site at -2.63 kb was a regulatory site responsible for the
      activation of IGFBP-1 gene promoter.

PMID- 7529732
TI  - cDNA cloning and mRNA expression of the six mouse insulin-like growth factor
      binding proteins.
AB  - The insulin-like growth factor binding proteins (IGFBPs) comprise a family of six
      distinct proteins which modulate insulin-like growth factor action. We have
      isolated cDNAs encoding the six mouse IGFBPs (mIGFBPs). In addition, we studied
      the mRNA expression of the six mIGFBPs during development and in various adult
      tissues. Our results show that each of the six mIGFBPs is highly homologous to
      their human and rat counterparts, whereas only the N and C terminal ends are
      conserved between the six mIGFBPs. Northern blotting revealed that mIGFBP-2, -3, 
      4 and -5 genes are already expressed at gestational day 11.5, suggesting a role
      for these mIGFBPs in embryonal development. In liver, a peak of mIGFBP-1 mRNA
      expression was found around birth, suggesting a function for mIGFBP-1 in the
      newborn mouse. Finally, tissue-specific expression of the six mouse IGFBP genes
      was observed in adult tissues suggesting different roles or modes of actions in
      adult life.

PMID- 7529733
TI  - Protein kinase C and insulin receptor beta-subunit serine phosphorylation in
      cultured foetal rat hepatocytes.
AB  - In digitonin-permeabilized cultured foetal hepatocytes, insulin receptor beta
      subunit was highly phosphorylated on serine residues in the presence of [gamma
      32P]ATP and Ca2+, a process enhanced after short exposure to insulin with no
      detectable insulin receptor autophosphorylation. By contrast with this situation,
      experiments performed with isolated foetal insulin receptors revealed an insulin
      stimulation of both serine phosphorylation and tyrosine autophosphorylation. In
      permeabilized cells, insulin receptor beta-subunit phosphorylation was increased
      after a 2-min exposure to phorbol 12-myristate 13-acetate (PMA) prior to applying
      the permeabilization/phosphorylation step, while it was inhibited by chronic
      treatment with PMA leading to protein kinase C (PKC) down modulation. The PKC
      specific inhibitor, GF109203X, strikingly reduced basal and insulin-enhanced
      phosphorylation of insulin receptor beta-subunit in permeabilized cells, but
      failed to exert any effect with isolated receptors. Labelling of glycogen from [U
      14C]glucose determined 1 h after a 10-min transitory exposure to insulin and/or
      modulators of PKC activity showed that PMA prevented insulin glycogenic response,
      whereas GF109203X was ineffective. Thus, although not directly responsible for
      insulin receptor serine phosphorylation in cultured foetal hepatocytes, PKC
      physiologically regulates this process which may inhibit insulin receptor
      tyrosine kinase activity. This regulation is independent of the antagonistic
      effect of PMA-activated PKC on insulin glycogenic response.

PMID- 7529735
TI  - Binding of HIV-1 gp120 to an anti-V3 loop antibody reveals novel antigen-induced
      epitopes.
AB  - Antigen association to its corresponding binding site in the immunoglobulin
      molecule can elicit conformational rearrangements, generating novel epitopes
      termed metatopes. Such metatopes were characterized for the immunocomplex between
      the AIDS virus envelope protein, gp120, and M77, a mAb directed against the V3
      loop. Five novel mAbs were described (GV1, GV3, GV7, GV8, and GV12). These mAbs
      were found to bind epitopes harbored in the M77 Fab fragment. Binding to the
      epitopes was shown to require the complexation of Fab with its antigen. The
      degree of this antigen requirement was found to be variable for the different
      mAbs and also for the state of IgG fragmentation. Binding of GV12 to its antigen
      increased the affinity of M77 for gp120. Moreover, in the presence of GV12, M77
      acquired extended cross-reactivity for a second gp120 variant, namely BaL. These
      results could indicate a novel approach towards improving the performance of anti
      HIV antibodies.

PMID- 7529734
TI  - Significance of membrane repolarization and cyclic AMP changes in mouse
      pancreatic B-cells for the inhibition of insulin release by galanin.
AB  - It is unclear whether the inhibition of insulin release by galanin is entirely
      explained by an interference with the secretory process at a step distal to the
      rise of cytoplasmic Ca2+ and to the action of second messengers in pancreatic B
      cells. In this study, normal mouse islets were used to assess the functional
      significance of the effects of galanin on other signalling pathways. In the
      presence of 15 mM glucose, galanin caused a small repolarization of the B-cell
      membrane and a sustained decrease in the Ca(2+)-dependent electrical activity.
      These changes were largely prevented by tolbutamide and by arginine. Under these
      conditions the concentration-dependence curve of galanin inhibition of insulin
      release was shifted to the right. The IC50 was increased 4-5-fold from a control
      value of 1.8 nM in the presence of glucose alone. This was not the case when
      insulin release was increased by cytochalasin B, an agent that acts on the
      filamentous cell web. We also evaluated the role of the changes in cAMP. To
      bypass the inhibition of adenylate cyclase produced by galanin, the islets were
      provided with exogenous, membrane permeant cAMP. When 10 mM glucose and 0.25 mM
      dibutyryl cAMP were combined, control insulin release was similar to that
      produced by 15 mM glucose alone. Neither the repolarization of the membrane nor
      the inhibition of insulin release by galanin were affected. A higher
      concentration of dibutyryl cAMP (0.5 mM) depolarized the B-cell membrane in the
      presence of 15 mM glucose and partially antagonized the effects of galanin on
      membrane potential and insulin release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529736
TI  - Three-dimensional structure and actions of immunosuppressants and their
      immunophilins.
AB  - The use of the immunosuppressant drug cyclosporin A (CsA) as a biochemical tool
      to study the signal transduction pathway in T cells has led to the discovery of a
      first family of immunosuppressant-binding proteins or "immunophilins," the
      cyclophilins (Cyp). Another, chemically unrelated immunosuppressant molecule,
      FK506, was then found to be related to a second class of immunophilins, the FK506
      binding proteins (FKBPs). This paper reviews the existing structural information
      on these immunophilins in the context of present knowledge of the biochemical
      mechanisms for immunosuppression. The formation of Cyp-CsA and FKBP-FK506
      complexes, and the subsequent specific interaction of these complexes with the
      serine/threonine phosphatase calcineurin (CN), are key steps in the cascade of
      events that result in the desired immunosuppression. Knowledge of the
      conformation of the Cyp-CsA-CN and FKBP-FK506-CN ternary complexes is of
      significant biomedical interest, because mimics of the composite contact surfaces
      of, for example, Cyp-CsA or FKBP-FK506, could provide immunosuppressant drugs
      with improved pharmacological profiles.

PMID- 7529737
TI  - The use of ubiquitin as a marker of thyroxine-induced apoptosis in cultured Rana
      catesbeiana tail tips.
AB  - Cultured Rana catesbeiana tadpole tail tips were used in combination with a
      fluoroimmunoassay to determine the levels of ubiquitin--a protein marker of
      programmed cell death in other systems--during the tissue regression induced by
      thyroxine (T4). After a 3-day pretreatment with the hormone, tail tips cultured
      in T4 showed significant increases in ubiquitin levels by 48 hr. Tail tips taken
      from tadpoles that had been immersed in T4 for 6 days showed a parallel increase
      in ubiquitin levels, demonstrating the same change in vivo. Treatment of cultured
      tail tips with the protein kinase C inhibitor, H-7, blocks both regression and
      the rise in ubiquitin seen in tips treated with T4 alone. Treatment of cultured
      tips with T4 and either cycloheximide or actinomycin D inhibits regression
      compared to T4 alone; however, the rise in ubiquitin is only blocked by
      cycloheximide, suggesting that ubiquitin is being made from RNA that was
      synthesized during the pretreatment period or earlier. These results suggest that
      ubiquitin will serve as a good molecular marker of tissue regression in the T4
      treated tadpole tail and that it will be productive to consider tissue regression
      during amphibian metamorphosis as a specific case of programmed cell death or
      apoptosis.

PMID- 7529738
TI  - Regulation of myelin basic protein-encoding gene transcription in rat
      oligodendrocytes.
AB  - The myelin (My) basic protein-encoding gene (MBP) is specifically expressed by
      oligodendrocytes (OL) in the central nervous system (CNS) and by Schwann cells in
      the peripheral nervous system (PNS). To define cell-type-specific regulatory
      elements, a series of chimaeric constructs containing varying lengths of the 5'
      flanking region and exon 1 of MBP linked to the cat reporter gene was transfected
      into several cell types, including primary cultures of differentiated rat OL,
      Schwann cells and kidney cells, as well as neuronal and non-neuronal cell lines.
      All the constructs generated variable levels of chloramphenicol acetyltransferase
      (CAT) activity in all cell types, except in primary OL and Schwann cells, where
      distinct positive (PRE) and negative regulatory elements (NRE) were found to be
      involved in regulating cat expression. The nucleotide (nt) -53/+70 construct gave
      maximal activity in all cell types, except OL and Schwann cells, where sequences
      upstream from nt -53 were necessary for maximal promoter activity. The sequences
      located at nt -655 to -397 and nt -394 to -54 showed enhancer and repressor
      effects, respectively, in OL. In Schwann cells, sequences from -394 to -253
      showed positive regulatory effects, while those between -655 to -397 and -253 to 
      54 showed negative regulatory effects. In the downstream region of the promoter,
      sequences from +20 to +70 and +70 to +200 showed strong silencer and enhancer
      activities specifically in OL. In gel-retardation assays using nuclear extracts
      prepared from several cell types and the -253 to -53 repressor sequences,
      specific DNA-protein complexes unique to OL were identified.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7529742
TI  - Significance of early intra-alveolar fibrotic lesions and integrin expression in
      lung biopsy specimens from patients with idiopathic pulmonary fibrosis.
AB  - To study the pulmonary structural remodeling in idiopathic pulmonary fibrosis
      (IPF), ultrastructural, immunohistochemical, and light microscopic morphometric
      observations were made on 11 pulmonary biopsy specimens from patients with IPF.
      The morphometric study was done using sequentially cut tissue sections stained
      for keratin-alcian blue periodic acid-Schiff (PAS), fibronectin, and type IV
      collagen-alcian blue PAS. Most of the early fibrotic lesions, which were alcian
      blue- and fibronectin-positive, were intra-alveolar in location. Intra-alveolar
      fibrosis is considered to be essential for the fusion of alveolar walls in IPF. A
      strong reaction for integrin alpha 5 beta 1 and vinculin was found in epithelial
      cells and mesenchymal cells in areas of intra-alveolar fibrosis. These findings
      show that these cells are active in adhesion to fibronectin in areas of early
      intra-alveolar fibrosis. Some of the epithelial cells, including cytoplasmic
      hyaline-laden cells, showed evidence of inadequate adhesion to the extracellular
      matrix, and this may constitute one of the mechanisms of progression of fibrosis
      in IPF.

PMID- 7529739
TI  - Three distinct messenger RNAs can encode the human immunosuppressant-binding
      protein FKBP12.
AB  - FKBP12 is an 11.8-kDa protein that binds the potent immunosuppressants FK506 and
      rapamycin. When bound to FK506, FKBP12 forms an inhibitory complex with
      calcineurin and interferes with signal transduction in activated T lymphocytes.
      In studying human FKBP12 cDNAs and the human FKBP12 gene, we found that three
      distinct transcripts can encode human FKBP12. The transcripts, which we designate
      FKBP 12A, 12B and 12C, contain identical open reading frames, but vary in
      abundance and are distinguished by unique 3' untranslated regions. The mature
      transcripts derive from either four or five exons and are generated by the
      differential use of one splice junction and three cleavage-polyadenylation sites
      within FKBP12. FKBP12A and 12B populations increase in abundance and/or stability
      when T-cell populations are mitogenically activated in vitro, implying that one
      result of T-cell stimulation is increased demand for the FKBP12 message. These
      transcripts are also present in a variety of human tissues, suggesting that
      FKBP12 and/or the mRNAs encoding it might affect physiological function(s) in a
      diverse array of cells.

PMID- 7529740
TI  - Enzymatic and chemical probing of an S1 nuclease-sensitive site upstream from the
      human CFTR gene.
AB  - Similar purine/pyrimidine mirror repeat (PMR) DNA sequences have been identified
      in the 5'-flanking regions of the human cystic fibrosis transmembrane conductance
      regulator (hCFTR) and mucin (hMUC1) genes, and supercoiled (but not linearized)
      plasmids containing these promoter regions were previously shown to be sensitive
      to digestion by S1 nuclease. The PMR element derived from the hCFTR promoter
      region is now sub-cloned and characterized at nucleotide resolution with respect
      to its reactivity toward nucleases S1 and P1, and toward the chemical probes
      dimethyl sulfate, chloroacetaldehyde, diethylpyrocarbonate and osmium tetroxide.
      These probes confirm the presence, at pH 4.5 (but not at pH 7.1), of a non-B-DNA
      structure. This non-B-DNA structure is distinct from H-DNA, because enzymatic and
      chemical probing detect single-stranded character in the absence of a stable
      intramolecular triple helix or extruded purine strand.

PMID- 7529741
TI  - A novel strategy using G-CSF to support EMA/CO for high-risk gestational
      trophoblastic disease.
AB  - EMA/CO (etoposide-methotrexate-actinomycin D and Cytoxan-Oncovin) is an effective
      and well-tolerated chemotherapy regimen for the treatment of high-risk
      gestational trophoblastic disease. However, it is associated with significant
      neutropenia often requiring dose reductions and treatment delays. We describe the
      use of granulocyte colony-stimulating factor (G-CSF) in three patients in order
      to maintain the treatment schedule. A subcutaneous injection of 5
      micrograms/kg/day was administered on Days 3-6 and 9-14 of each chemotherapy
      cycle. No patients had any adverse effects and all received full chemotherapy
      doses without any treatment delay. The addition of G-CSF to the EMA/CO regimen
      may benefit patients by achieving dose intensity in the treatment of high-risk
      gestational trophoblastic disease.

PMID- 7529743
TI  - Influence of Gm allotype on the IgG subclass response to streptococcal M protein
      and outer membrane proteins of Moraxella catarrhalis.
AB  - The IgG antibody response to streptococcal M protein is distributed between the
      IgG1 and IgG3 subclasses, however individual sera vary with respect to the
      relative amounts of these two subclasses. The basis of this variation was
      investigated. Sera were also analysed for IgG subclass antibodies to the outer
      membrane proteins (OMP) of Moraxella catarrhalis, as these have also been
      reported to have a major IgG3 component. The mean percentage of IgG3 was higher
      in the antibody response to OMP and there was less variability between sera for
      this antigen than was seen for M protein. Non-specific binding of IgG3 in ELISA,
      which has been reported for some bacterial proteins (including M protein of some
      serotypes) was excluded as an explanation for the apparent IgG3 bias of these
      antibodies. The relative amount of IgG3 antibody to the two antigens showed a
      positive correlation, suggesting that some individuals tended to make a greater
      IgG3 response to unrelated antigens. Serial bleeds from two individuals
      maintained a relatively constant subclass profile over several months, suggesting
      that time since infection did not play a major role in determining the proportion
      of IgG1 and IgG3. Gm allotypes for the sera were determined, and found to
      correlate with both total serum IgG3 concentrations and with IgG subclass
      composition of specific antibodies. Mean serum IgG3 concentrations were highest
      in sera typed as Gm(fb/fb) homozygous and lowest in sera typed as Gm(ag/ag)
      homozygous. Similarly, in the M protein-specific antibodies, the mean percentage
      of IgG3 was much lower in the Gm(ag/ag) sera than in the Gm(fb/fb) homozygous
      sera. Sera which typed as Gm(fb/ag) heterozygous were not significantly different
      from the Gm(fb/fb) homozygous sera for either total serum IgG3 or for M protein
      specific IgG3. Moreover, both Gm(fb/fb) homozygous and Gm(fb/ag) heterozygous
      sera included samples in which IgG1 was the predominant antibody subclass and the
      percentage of IgG3 was very low. In contrast to the M protein-specific
      antibodies, for the OMP-specific antibodies there was no correlation between Gm
      phenotype and the proportion of IgG3. The data suggest that Gm allotype may
      influence the IgG subclass composition of antibody responses to bacterial surface
      protein, but that other factors are also likely to be involved.

PMID- 7529744
TI  - Modulation of the Fc gamma RII and Fc gamma RIII induced by GM-CSF, IFN-gamma and
      IL-4 on murine eosinophils.
AB  - Murine eosinophils express the low-affinity Fc gamma receptors recognized by the
      monoclonal antibody (mAb) 2.4G2, which are involved in the activation of these
      cells. We have studied the membrane and RNA expression of the low-affinity Fc
      gamma receptors on murine eosinophils stimulated by granulocyte-macrophage colony
      stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), and interleukin-4 (IL
      4). Flow cytometric analysis (FACS) of eosinophils incubated with GM-CSF and IFN
      gamma showed an up-regulation on the expression of these receptors with a maximal
      effect at 24 hr. IL-4 failed to induce any positive or negative effect in these
      cells. To assess the pattern of expression of the low-affinity Fc gamma receptors
      on eosinophils, Northern blot analyses were carried out using specific cDNA
      probes encoding for the Fc gamma RII and Fc gamma RIII. Murine eosinophils
      constitutively express transcripts for Fc gamma RII and RIII. Incubation with GM
      CSF from 3 to 12 hr produced a potent induction of the two transcripts studied
      (Fc gamma RII and RIII). IFN-gamma did not induce any important up-regulation of
      the two transcripts from 3 to 12 hr of incubation. By contrast, IL-4 produced a
      marked inhibition of both transcripts at 24 hr of incubation. Expression of the
      gamma-chain transcript which is associated with Fc gamma RIII has been detected
      on freshly isolated eosinophils. This study demonstrates a different regulation
      pattern of these receptors depending on the cytokine or growth factor used to
      stimulate murine eosinophils.

PMID- 7529745
TI  - Acetylation (O-factor 5) affects the structural and immunological properties of
      Salmonella typhimurium lipopolysaccharide O antigen.
AB  - The lipopolysaccharide (LPS) of gram-negative bacteria serves as a barrier
      between the cell and its environment. The LPS O antigen is the immunodominant
      portion of the molecule and thus has a significant effect on the interaction
      between a bacterial pathogen and the host organism. Antibodies directed against O
      antigen are vital to the immune response to infection. In this study, we have
      characterized the interaction between a series of monoclonal immunoglobulin A
      antibodies and the LPS of Salmonella typhimurium. Using one of these antibodies,
      we have previously shown that monoclonal immunoglobulin A is sufficient to
      protect against S. typhimurium infection, both in vivo and in vitro. Here, we
      show that recognition of LPS by the monoclonal antibodies is affected by
      acetylation of the O antigen on the abequose moiety, the determinant of the O5
      epitope. Although recognition of LPS by several of the monoclonal antibodies is
      completely dependent on acetylation, the antibodies recognize clearly separable
      epitopes. This suggests that acetylation of O antigen affects the three
      dimensional structure of the molecule and thus creates and destroys a series of
      conformational antigenic determinants. We have shown that a change in the
      acetylation state of LPS has no effect on virulence. However, acetylation has
      important consequences for the mucosal immune response and thus could potentially
      have profound implications for the ability of an immune host to respond to a
      subsequent infection.

PMID- 7529750
TI  - Circles: concerning circles in nature, circles produced by man, and circles in
      dermatology.

PMID- 7529746
TI  - CD14 is not involved in Rhodobacter sphaeroides diphosphoryl lipid A inhibition
      of tumor necrosis factor alpha and nitric oxide induction by taxol in murine
      macrophages.
AB  - Taxol, a microtubule stabilizer with anticancer activity, mimics the actions of
      lipopolysaccharide (LPS) on murine macrophages in vitro. Recently, it was shown
      that taxol-induced macrophage activation was inhibited by the LPS antagonist
      Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA). To investigate the
      mechanisms of taxol-induced macrophage activation, the present study focused on
      the interaction of LPS, RsDPLA, and taxol in the activation of and binding to
      macrophages. Taxol alone induced murine C3H/He macrophages to secrete tumor
      necrosis factor alpha (TNF) and to produce nitric oxide (NO) with kinetics
      similar to that of LPS. Macrophages from LPS-hyporesponsive C3H/HeJ mice, in
      contrast, did not yield any detectable TNF and NO production in response to LPS
      or taxol. RsDPLA inhibited taxol-induced TNF and NO production from C3H/He
      macrophages in a dose-dependent manner. The inhibition by RsDPLA was specific for
      LPS and taxol in that RsDPLA did not inhibit heat-killed Listeria monocytogenes-
      or zymosan-induced TNF production. Polymyxin B blocked the inhibitory effect of
      RsDPLA on taxol-induced TNF production. The inhibitory activity of RsDPLA
      appeared to be reversible since macrophages still responded to taxol in inducing
      TNF production after the RsDPLA was washed out with phosphate-buffered saline
      prior to the addition of taxol. Taxol-induced TNF production was not inhibited by
      colchicine, vinblastine, or 10-deacetylbaccatine III. A mutant cell line,
      J7.DEF3, defective in expression of a CD14 antigen, responded equally well to
      taxol by producing TNF as did the parent J774.1 cells. This suggested that the
      activation of macrophages by taxol does not require CD14. Taxol-induced TNF
      production by the mutant cells was also inhibited by RsDPLA. 125I-labeled LPS and
      3H-labeled taxol was reported to bind to J774.1 cells predominantly via CD14 and
      microtubules, respectively. The binding of 125I-labeled LPS to J7.DEF3 cells was
      about 30 to 40% of that to J774.1 cells. The binding of 125I-LPS to J774.1 cells
      was inhibited by unlabeled LPS and RsDPLA but not by taxol. On the other hand, 3H
      labeled taxol bound to both J774.1 cells and J7.DEF3 cells in similar time- and
      dose-dependent manners. The binding of [3H]taxol to these cells was inhibited by
      taxol but not by LPS or RsDPLA. Although the binding studies failed to examine
      cross competition for binding to macrophages, a possible explanation of these
      results is that LPS, RsDPLA, and taxol share the same molecule(s) on murine
      macrophages for their functional receptor(s), which is neither CD14 nor tubulin.

PMID- 7529747
TI  - Induction of serine and threonine protein phosphorylation by endotoxin-associated
      protein in murine resident peritoneal macrophages.
AB  - Endotoxin-associated protein (EP) from Salmonella typhi activated murine resident
      peritoneal macrophages to produce prostaglandin E2 (PGE2). Cells from both
      endotoxin nonresponder (C3H/HeJ) and the endotoxin responder (C3H/OuJ) mouse
      strains were activated by EP. This EP-induced prostaglandin E2 production was
      blocked by the protein kinase C (PKC) inhibitor H-7 as well as the tyrosine
      kinase inhibitor genistein, suggesting the involvement of both serine and
      threonine phosphorylation and tyrosine phosphorylation pathways in the activation
      of resident peritoneal macrophages by EP. Immunoblot analysis using
      antiphosphoserine and antiphosphothreonine antibodies showed that EP induced the
      serine and threonine phosphorylation of a 14-kDa protein (p14). This
      phosphorylation was not induced by phorbol myristic acid or by lipopolysaccharide
      endotoxin. Inhibitors of PKC, PKA, and PKG did not block the phosphorylation of
      p14. However, the tyrosine kinase inhibitor piceatannol blocked p14 serine and
      threonine phosphorylation, suggesting that this phosphorylation is dependent upon
      and preceded by a tyrosine phosphorylation step.

PMID- 7529749
TI  - Effects of nitric oxide synthase inhibitors on murine infection with
      Mycobacterium tuberculosis.
AB  - We have recently demonstrated that the macrophage L-arginine-dependent cytotoxic
      pathway effectively kills the virulent Erdman strain of Mycobacterium
      tuberculosis in vitro via the generation of toxic reactive nitrogen intermediates
      by the enzyme nitric oxide synthase. This report demonstrates that two distinct
      inhibitors of nitric oxide synthase (aminoguanidine and NG-monomethyl-L-arginine)
      render similar deleterious effects on tuberculous infection in mice, as assessed
      by mortality, bacterial burden, and pathological tissue damage, thus confirming
      the importance of reactive nitrogen intermediates in resistance against M.
      tuberculosis.

PMID- 7529748
TI  - Regulation of staphylococcal enterotoxin B-elicited nitric oxide production by
      endothelial cells.
AB  - The effect of staphylococcal enterotoxin B (SEB)-elicited inducible nitric oxide
      synthase (iNOS) in mouse endothelial cells was investigated. Results showed that
      SEB stimulated the same level of NO production in gamma interferon (IFN-gamma)
      primed cells as did trichloroacetic acid-extracted lipopolysaccharide. The
      kinetics of induced NO production and expression of mRNA for iNOS differed
      markedly in endothelial and macrophage cells. Induced endothelial nitrite
      production was transient and was 15 to 20% of that generated by macrophage cells;
      mRNA levels peaked by 2 h and then steadily declined, whereas macrophage message
      levels continually increased. The ability of endothelial cells to produce SEB
      induced NO depended on priming with IFN-gamma, although detectable mRNA could be
      elicited by SEB alone. Induction of endothelial iNOS mRNA was inhibited by
      cycloheximide, which indicated a requirement for de novo protein synthesis.
      Niacinamide and interleukin-10 significantly reduced SEB-induced endothelial NO
      production. Both are reported to affect IFN-gamma-induced class II major
      histocompatibility complex (MHC) expression on antigen-presenting cells.
      Niacinamide reduced iNOS mRNA levels and markedly reduced IFN-gamma induction of
      endothelial class II MHC surface antigen. Interleukin-10 did not consistently
      reduce iNOS mRNA expression and had no effect on IFN-gamma induction of
      endothelial class II MHC surface antigen. These results suggest that SEB
      interacts with IFN-gamma-primed endothelial cells to elicit induced NO and that
      this induction can be effectively modulated at the receptor or transcriptional
      level.

PMID- 7529751
TI  - 1H and 31P NMR spectroscopy of phosphorylated model peptides.
AB  - The model peptides glycylglycyltyrosylalanine (Gly-Gly-Tyr-Ala),
      glycylglycylthreonylalanine (Gly-Gly-Thr-Ala) and glycylglycylserylalanine (Gly
      Gly-Ser-Ala) were phosphorylated at the hydroxyl groups of their tyrosyl,
      threonyl and seryl residues, respectively, and characterized by 31P and 1H NMR
      spectroscopy. The pKa-value of the phosphoryl group in the tyrosine-containing
      peptide determined from the pH dependence of chemical shifts is 5.9, the 31P
      chemical shifts at low pH (4.0) and high pH (8.0) are -3.8 and 0.2 ppm,
      respectively. Phosphorylation also leads to significant shifts of the 1H NMR
      resonances of the tyrosine residue; the amide resonance is shifted -0.02 ppm, the
      H alpha resonance 0.06 ppm, the H beta resonances 0.10 and -0.04 ppm, the H delta
      resonances 0.02 ppm and the H epsilon resonances 0.26 ppm. The pKa-value of the
      phosphoryl group in the threonine peptide determined from the pH dependence of
      chemical shifts is 6.1; the 31P chemical shifts at low pH (4.0) and high pH (8.0)
      are -0.1 and 4.8 ppm, respectively. The corresponding values for the serine
      peptide are 6.1 (pKa), 0.6 ppm and 4.9 ppm. Phosphorylation also leads to
      significant shifts of the 1H NMR resonances of the threonine and serine residues.
      In the threonine residue the amide resonance is shifted 0.25 ppm, the H alpha
      resonance -0.43 ppm, the H beta-resonance 0.03 ppm and the H gamma-resonance 0.09
      ppm. In the serine residue the amide resonance is shifted 0.21 ppm, the H alpha
      resonance -0.17 ppm, and the H beta-resonances 0.17 ppm.

PMID- 7529754
TI  - Topical bleomycin treatment of oral leukoplakia: a randomized double-blind
      clinical trial.
AB  - BACKGROUND: Oral leukoplakia and oral erythroplakia may be associated with benign
      and dysplastic cellular changes, and are at risk of malignant transformation.
      Additional means of management of these lesions is needed. The results of
      nonblinded trials using topical bleomycin in oral leukoplakia indicated the need
      for phase III study. METHODS: A prospective, double-blind, randomized trial of
      topical bleomycin versus placebo was conducted. Bleomycin 1% in
      dimethylsulphoxide (DMSO) or the carrier was applied for 5 minutes for 14
      consecutive days. Clinical assessment and pre-application and post-treatment
      biopsies were conducted. RESULTS: Twenty-two patients were randomized. Of the
      patients who received bleomycin, decrease in clinical size of the lesion was
      achieved (p = 0.001), and histological reduction in dysplasia was seen (p =
      0.094). CONCLUSIONS: The topical application of bleomycin in DMSO may represent
      an additional approach to management of oral leukoplakia. The treatment is well
      tolerated, and may be considered when the location or extent of the lesion may
      make surgical excision difficult.

PMID- 7529752
TI  - Characterization of vasoactive intestinal peptide receptors in rabbit ciliary
      processes.
AB  - PURPOSE: To demonstrate a potential role for vasoactive intestinal peptide (VIP)
      in the regulation of ciliary process function, VIP receptors on rabbit ciliary
      process membranes were identified and characterized in biochemical and
      immunochemical studies. METHODS: Membranes were isolated from rabbit ciliary
      processes, and VIP receptors were characterized by competition binding, affinity
      cross-linking, and N-glycanase digestion. A site-specific polyclonal antibody
      directed against the NH2-terminal end of the deduced sequence of the recently
      cloned rat VIP receptor was generated and used to identify the VIP receptor by
      immunoblot analysis. RESULTS: Membranes isolated from rabbit ciliary processes
      exhibited a high-affinity VIP binding site (KD approximately 1 nM). Secretin and
      glucagon, which possess considerable primary sequence homology with VIP, were
      ineffective in inhibiting 125I-VIP binding to ciliary process membranes. In
      conjunction with the chemical cross-linking agent disuccinimidyl suberate, 125I
      VIP specifically labeled a 63-kd protein in membranes from ciliary processes.
      This apparent size was confirmed by immunoblot analysis of ciliary body membranes
      using a site-specific polyclonal antibody that recognizes residues 92 to 104 of
      the rat VIP receptor. Digestion of the affinity-labeled receptor with N-glycanase
      generated an N-linked oligosaccharide free core protein of -50 kd. CONCLUSIONS:
      These findings demonstrate the presence of specific VIP receptors in rabbit
      ciliary processes. The differences in ligand specificity and structure of the
      ciliary process VIP receptor, compared to VIP receptors on peripheral tissues,
      suggest either a specific role(s) for VIP that may be unique to the anterior
      segment or the existence of VIP receptor isoforms.

PMID- 7529753
TI  - Vitamin D inhibits angiogenesis in transgenic murine retinoblastoma.
AB  - PURPOSE: Vitamin D compounds have been shown to inhibit tumor growth in a
      transgenic retinoblastoma murine model. The mechanism of action has not been
      defined clearly, although an antiangiogenic action has been proposed. METHODS:
      Transgenic retinoblastoma mice received high (0.05 microgram) and low (0.025
      microgram) doses of vitamin D3 by intraperitoneal injection 5 times per week for
      5 weeks. Control animals were injected with mineral oil vehicle alone. At 5
      months of age, the animals were killed and eyes were enucleated and processed for
      light microscopy. Paraffin-embedded sections were stained with an
      immunoperoxidase stain (GS-1) specific for mammalian vascular endothelium.
      Sections were graded by a single masked reviewer, and intraobserver reliability
      was assessed. Mean vessel counts were made for each group. RESULTS: The high-dose
      group had the lowest mean vessel count (8.5), followed by the low-dose group
      (10.1). The control group had the highest mean vessel count (14.1). Vitamin D
      treated animals (high- and low-dose groups combined) had significantly fewer
      vessels P = 0.001) than untreated controls. CONCLUSIONS: These results support
      the hypothesis that inhibition of angiogenesis is a mechanism of action for
      vitamin D in the transgenic retinoblastoma mouse model.

PMID- 7529755
TI  - Differential staining of nerve cells and fibres for sections of paraffin-embedded
      material in mammalian central nervous system.
AB  - A differential staining method is described of myelinated fibres and nerve cell
      bodies applicable to sections of mammalian, including human, central nervous
      system specimens embedded in paraffin wax. Experimental and human necropsy
      material fixed in acetic paraformaldehyde in phosphate buffer was used. Sections
      of 15-20 microns in thickness were obtained, attached to slides, deparaffinized
      and hydrated. After hydration, sections are oxidized (30 s) in 2% potassium
      permanganate, bleached (1 min) in 5% oxalic acid and rinsed in distilled water.
      Staining is for 2-5 h in the following solution: 0.06% thionin, 1% formaldehyde,
      10% acetic acid in distilled water. Sections are subsequently washed in distilled
      water, dehydrated through 96% and absolute ethanol, cleared in eucalyptol and
      mounted in Eukitt. Using the method described in the present paper, a
      differential coloration of myelin and neurons is obtained. Myelinated fibres
      appear red, whereas nerve cell bodies and glial nuclei are stained blue. This
      procedure provides a high contrast between myelin and cells suitable for
      observation and photography of sections. Simultaneous and differential coloration
      of both myelin and cells is easily and directly obtained with constant and
      homogeneous results.

PMID- 7529757
TI  - Localization of nitric oxide synthase immunoreactivity in mast cells of human
      nasal mucosa.
AB  - Nitric oxide (NO)-synthase immunoreactivity has been detected for the first time
      in mast cells of human normal nasal mucosa, with an antibody specific for
      neuronal NO-synthase. Intense immunoreactivity was revealed in secretion granules
      of mast cells but was found in mast cell granules free in the extracellular
      matrix only in some instances; no reactivity was found in the cytoplasm of this
      or other cell types. These findings suggest that human nasal mast cells contain a
      particulate isoform of NO-synthase, which shares epitopes with neuronal NO
      synthase and is rapidly removed from granules upon exocytosis.

PMID- 7529756
TI  - DNA stainability with base-specific fluorochromes: dependence on the DNA topology
      in situ.
AB  - The influence of DNA topology on stainability with the externally binding
      fluorochromes Hoechst 33258 (HO) and mithramycin (MI) was investigated in HeLa
      nuclei in comparison with the intercalating dye propidium iodide (PI). Changes in
      DNA topology were induced with a mild DNAse I treatment. Stainability properties
      of untreated and nuclease-treated nuclei were compared with those of the
      supercoiled-circular and the relaxed-linear forms of the plasmid pBR322. DNAse
      treated nuclei stained with HO showed a higher fluorescence intensity than
      control samples, independently of the dye concentration, in contrast with the
      findings obtained with PI. Similar behaviour was observed with the relaxed-linear
      form of pBR322, compared with the supercoiled-circular molecule. With MI, the
      stainability of HeLa nuclei did not depend on the DNA topology, whereas the
      stainability of the plasmid was similar to that of HO. In order to assess whether
      this discrepancy depended on differences in the availability of DNAse-sensitive
      sites to the fluorochromes, fluorescence resonance energy transfer (FRET) studies
      were performed in nuclei stained with HO+PI, or with HO+MI dye pairs. After DNAse
      I digestion, the relative FRET efficiency between donor (HO) and acceptor
      molecules (PI or MI) was reduced significantly only when MI was the acceptor.
      This result may be due to greater stainability of DNAse-sensitive sites with HO
      than with MI. These findings indicate that DNA stainability with base-specific
      fluorochromes may be affected by the topology of chromatin regions.

PMID- 7529759
TI  - Different regulation and expression of the human CYP2E1 gene due to the RsaI
      polymorphism in the 5'-flanking region.
AB  - The effects of two genetically associated polymorphisms [c1 allele: PstI -, RsaI
      +; c2 allele: PstI +, RsaI -] in the 5'-flanking region on the regulation and
      expression of the human CYP2E1 gene were investigated. DNase I footprinting and
      CAT activity analyses using various deletion mutants constructed with DNA
      segments from genotype A (c1/c1) or C (c2/c2) and SV40 or an endogenous promoter
      showed that the RsaI polymorphism affects the binding of a transcription factor
      and the transcriptional activation of CYP2E1, while the PstI polymorphism has
      little effect. The correlation between the genotypes and expression levels of
      CYP2E1 mRNA were examined in peripheral lymphocytes of 86 individuals by RT-PCR,
      the alcohol consumption by the subjects being taken into account. In non
      drinkers, the mean ratio of the expression of CYP2E1 mRNA to that of GAPDH mRNA
      in genotype B (c1/c2) was 1.7-fold higher than that in genotype A (0.05 < p <
      0.10). As compared to non-drinkers with genotype A, subjects with genotype B who
      drank alcohol on a daily basis expressed about 2.0-fold higher levels of CYP2E1
      mRNA (p < 0.01). These results indicate that a RsaI polymorphism in the 5'
      flanking region of CYP2E1 may lead to inter-individual differences in CYP2E1
      mediated microsomal drug oxidation activities, including oxidation of N
      nitrosamines.

PMID- 7529760
TI  - Regulation of Src family kinases in the developing rat brain: correlation with
      their regulator kinase, Csk.
AB  - We have so far suggested that the functions of Src family protein-tyrosine
      kinases are under the control of their regulator kinase, Csk. To evaluate the
      role of Csk-mediated regulation in neural tissues, we examined the correlation
      between the activities of Src family kinases and the expression level of Csk
      during development of the rat brain. Csk was expressed at high levels in the
      developing embryonic brain and then rapidly decreased as the brain matured.
      Consistent with the decrease in the Csk level, the kinase activity of a member of
      the Src family, Fyn, was greatly enhanced, but that of Src was not correlated
      inversely with the level of Csk expression. Src exhibited elevated activity in
      the developing brain, in which a neuronal form of Src (N-Src) is expressed as the
      dominant form of Src. Although N-Src was readily down-regulated by Csk when
      coexpressed in yeast, it showed much higher specific activity than c-Src, even in
      the repressed form. These findings suggest that neural tissues acquire high
      activities of Src family kinases, which might be important for differentiation
      and development of the nervous system, through induction of the active form of
      Src (N-Src) and down-regulation of their suppresser, Csk.

PMID- 7529758
TI  - Distribution of serotonin-immunoreactive gut endocrine cells in chicks at
      hatching. Examination of possible co-localisation with peptides reveals
      unexpected cross-reactivity of substance P antiserum with serotonin.
AB  - Serotonin-immunoreactive, i.e. enterochromaffin (EC) cells were found to be
      widely distributed in the intestine of the newly hatched chick but sparse in the
      stomach, and being particularly abundant in the duodenum, upper ileum and rectum.
      Although in birds, as in mammals, EC cells are most abundant in the intestine, in
      the stomach they are far sparser than in mammals. Comparison of adjacent sections
      immunostained for serotonin and a peptide provided no evidence that EC cells in
      the hatching chick contain motilin or substance P, and that at least the great
      majority of bombesin-immunoreactive cells contain no serotonin: it is apparent
      that the mammalian pattern of distribution of peptides in EC cells does not occur
      in the chick, at least at hatching. Cross reaction of an antiserum to substance P
      with serotonin was discovered, suggesting the need for a review of existing
      evidence for co-localisation of this peptide with serotonin.

PMID- 7529761
TI  - Evidence that the heparin-binding consensus sequence of vitronectin is recognized
      by Staphylococcus aureus.
AB  - Binding of heparin-binding form of vitronectin to Staphylococcus aureus was
      inhibited completely by heparin or by the same form of vitronectin. The binding
      was inhibited only to about 50% by the non-heparin-binding form of vitronectin,
      indicating an apparent involvement of the heparin-binding properties in the
      interaction between vitronectin and S. aureus. This was supported by experiments
      in which a synthetic peptide (Ala347-Arg361, comprising heparin-binding consensus
      sequences) was found to partly inhibit bacterial adherence to immobilized
      vitronectin. A bacterial cell surface protein could bind to the
      quinquedecapeptide, but not to the highly charged peptides consisting entirely of
      arginine or lysine, immobilized on microtiter plates and the binding could be
      competitively inhibited by an excess of soluble peptide. Direct binding of
      radiolabeled peptide to bacterial cells was also demonstrated, which was rapid,
      saturable, and pH-dependent. Furtherly a bacterial surface protein having
      molecular mass of 60 kDa was isolated by affinity chromatography on a
      quinquedecapeptide-HiTrap-NHS column. Our data suggest that the heparin-binding
      properties of vitronectin play a role in bacterial recognition.

PMID- 7529762
TI  - The formation of the 2',5'-phosphodiester linkage in the cDNA priming reaction by
      bacterial reverse transcriptase in a cell-free system.
AB  - Bacterial reverse transcriptase (RT) is responsible for synthesis of multicopy
      single-stranded DNA (msDNA) consisting of single-stranded DNA linked to an
      internal guanosine residue of RNA by an unusual 2',5'-phosphodiester linkage.
      Here we purified a bacterial RT to homogeneity from Escherichia coli harboring
      the RT gene from retron-Ec73. The purified RT-Ec73 was able to synthesize msDNA
      in a cell-free system using an RNA template produced in vitro by T7 RNA
      polymerase. The in vitro synthesized msDNA was released from the template RNA
      only when treated with yeast debranching enzyme DBR1, a specific nuclease for a
      2',5'-phosphodiester linkage. The position of the branching G residue in the
      template RNA and the DNA sequence of the cell-free product were identical to
      those of msDNA-Ec73 synthesized in vivo. These results clearly demonstrate that
      the formation of the 2',5'-phosphodiester linkage in msDNA synthesis is carried
      out by RT itself.

PMID- 7529763
TI  - Kinetics and mechanism of tetrahydrobiopterin-induced oxidation of nitric oxide.
AB  - A Clark-type nitric oxide-sensitive electrode was used for electrochemical
      determination of NO oxidation kinetics. Reaction with molecular oxygen followed
      second-order rate law with respect to NO with an overall rate constant of 9.2 +/-
      0.33 x 10(6) M-2 s-1. Tetrahydrobiopterin, an essential cofactor of NO synthases,
      was found to induce rapid oxidation of NO in a 1:1 stoichiometry. The reaction
      required the presence of oxygen, was zero order with respect to NO and first
      order with respect to tetrahydrobiopterin, completely blocked by 5,000 units/ml
      superoxide dismutase, and mimicked by a superoxide-generating system. Purified
      brain NO synthase produced no detectable NO unless high amounts of superoxide
      dismutase were present. NO synthase-catalyzed citrulline formation was inhibited
      by superoxide dismutase (5,000 units/ml) in an oxyhemoglobin-sensitive manner,
      indicating that NO induces feedback inhibition of NO synthase. NO-stimulated
      soluble guanylyl cyclase was inhibited by tetrahydrobiopterin at half-maximally
      active concentrations of 2 microM. The present data suggest that NO is
      inactivated to peroxynitrite by superoxide generated in the course of
      tetrahydrobiopterin autoxidation.

PMID- 7529764
TI  - The 70-kDa heat shock proteins associate with glandular intermediate filaments in
      an ATP-dependent manner.
AB  - Keratin polypeptides 8 and 18 (K8/18) are intermediate filament proteins
      expressed preferentially in glandular epithelia. We describe the identification,
      by co-immunoprecipitation from normal human colonic tissues and cultured cell
      lines, of the 70-kDa heat shock protein (hsp) and its related heat shock cognate
      protein as K8/18-associated proteins (hsp/c). The association is significant but
      sub-stoichiometric and occurs preferentially with the soluble rather than the
      cytoskeletal K8/18 fractions. Heat stress increases the level of soluble K8/18 in
      association with an increase in hsp70 levels and an increase in the stoichiometry
      of K8/18-hsp70 association. Identity of the associated proteins was confirmed by
      microsequencing of a tryptic digest of the purified associated protein and by
      using anti-hsp/c70-specific antibodies. The K8/18-hsp/c70 complex can be
      dissociated in a Mg-ATP-dependent manner that requires ATP hydrolysis. Binding of
      hsp to K8/18 can be reconstituted using purified bovine hsp70 and human K8/18
      immunoprecipitates that have been depleted of bound hsp/c70 and increases
      slightly in the presence of ATP. The reconstituted K8/18-hsp70 complex can be
      again released in the presence of Mg-ATP. In addition, hsp70 binds to K8/18
      without having a significant effect on in vitro filament assembly when added
      during or after assembly. Using an overlay assay, hsp70 binds exclusively to K8
      in the presence of ATP. Our results show direct association of the hsp/c70
      proteins with K8/18. This interaction may serve, at least in part, to regulate
      the function of these two abundant protein groups.

PMID- 7529766
TI  - Expression of an epidermal keratin protein in liver of transgenic mice causes
      structural and functional abnormalities.
AB  - To examine the role of keratin intermediate filament proteins in cell structure
      and function, transgenic mice were isolated that express a modified form of the
      human K14 keratin protein in liver hepatocytes. A modified K14 cDNA (K14.P)
      sequence was linked downstream of the mouse transthyretin (TTR) gene promoter and
      enhancer elements to achieve targeted expression in hepatocytes. Hepatocytes
      expressing high levels of the transgene were found to have abnormal keratin
      filament networks as detected by indirect immunofluorescence using an antibody
      specific for the transgene product. Light and electron microscopic level
      histological analysis of isolated liver tissue showed in many cases degenerative
      changes that included inflammatory infiltration, ballooning degeneration, an
      increase in fat containing vacuoles, and glycogen accumulation. These changes
      were most evident in older mice over four months of age. No indication of typical
      Mallory body structures were identified at either the light or electron
      microscopic level. To evaluate secretory function in transgenic livers, bile acid
      secretion rates were measured in isolated perfused liver and found to be
      approximately twofold lower than aged-matched controls. These findings indicate
      that expression of an abnormal keratin in liver epithelial cells in the in vivo
      setting can alter the structure and function of a tissue and suggest a role of
      the keratin network in cellular secretion.

PMID- 7529765
TI  - Refolding and reconstitution of functionally active complexes of human leukocyte
      antigen DR2 and myelin basic protein peptide from recombinant alpha and beta
      polypeptide chains.
AB  - Major histocompatibility complex (MHC) class II molecules are cell surface
      heterodimeric glycoproteins consisting of one alpha and one beta polypeptide
      chain of similar size. These molecules play a critical role in immune recognition
      by displaying processed antigens to CD4-positive T helper cells. Several attempts
      to express the MHC class II molecules by recombinant methods in various systems
      resulted in either failure or poor recovery of the intact heterodimer. The
      present study describes our successful effort to refold and reconstitute HLA DR2
      heterodimer from individually expressed alpha and beta polypeptide chains lacking
      the transmembrane hydrophobic regions in Escherichia coli, in the presence of an
      immunodominant epitope analog from human myelin basic protein (b-MBP(83-102)Y83).
      The reconstituted DR2 heterodimer complex was selectively purified from unfolded
      alpha and beta chains using heterodimer-specific monoclonal antibody (L243)
      coupled to a solid support. The detection of two polypeptide chains in the
      purified refolded DR2-peptide complex preparations was accomplished by Western
      blot analysis and enzyme-linked immunosorbent assay using heterodimer- and chain
      specific polyclonal antibodies, and the presence of equimolar amounts of both
      alpha chain and beta chain in the reconstituted complex preparation was confirmed
      by a double label experiment. The quantitation of the bound peptide in complex
      preparation was measured by incubating two chains in the presence of 125I-labeled
      peptide. An increase in the yield of refolded and reconstituted DR2-peptide
      complexes was observed with increasing peptide concentration in the reaction
      mixture. Finally, the functional activity of the reconstituted DR2 complexes was
      measured by their ability to stimulate gamma-interferon production by SS8T cloned
      T cells in an antigen-specific and dose-dependent manner. These results
      demonstrate that biologically active complexes of human DR2.b-MBP (83-102)Y83 can
      be prepared by proper folding of human leukocyte antigen DR2 alpha and beta
      chains in the presence of antigenic peptide. The yield of such DR2 heterodimers
      with bound peptide is several thousand-fold higher over native DR2 purified from
      transformed B cells. Since purified MHC class II-peptide complexes have been
      shown to prevent autoimmune diseases in various animal models, reconstituted
      heterodimer complexes may have significant clinical relevance in antigen-specific
      treatment of various autoimmune diseases. In addition, such complexes with
      increased yield will provide better understanding of the trimolecular
      interactions between MHC-peptide and T cell receptor.

PMID- 7529768
TI  - Control of cell cycle entry and progression in mitogen-stimulated human B
      lymphocytes.
AB  - Tonsillar B lymphocytes were stimulated to proliferate by the mitogenic
      combination of phorbol dibutyrate and ionomycin. Progression through the cell
      cycle was monitored by measurements of cellular DNA and RNA content using flow
      cytometry. Changes in surface expression of class II MHC antigens and CD20
      antigen were also monitored as early parameters of B lymphocyte activation and
      cell cycle progression. The results showed that about 60% of the population
      synchronously entered and progressed through the cell cycle. The transition from
      the resting state, signaled by increased RNA content, occurred about 12 to 24 hr
      after stimulation; S phase entry occurred at about 36 hr. Small, variable
      populations of cells appeared to be unresponsive to the stimuli, either because
      they were "preactivated" before in vitro stimulation or were already dying. The
      kinetics of appearance and accumulation of several cell cycle
      regulated/regulatory proteins were followed by immunoblotting. The proliferating
      cell nuclear antigen (PCNA) cyclin A and p33cdk2 proteins were either absent or
      present in very low amounts in resting cells and first became detectable in
      increased amount beginning at about 24 hr after stimulation; increased p34cdc2
      protein was not detected until about 36 hr. Increased cellular content and
      phosphorylation of the p110Rb protein was already obvious by 24 hr after
      stimulation. The effects of several immunosuppressive agents were examined using
      purified B cells. Both cyclosporin A and an FK506 analogue were shown to inhibit
      proliferation of B lymphocytes, at the low doses also inhibitory to T cells.

PMID- 7529767
TI  - In vitro structural and functional relationships between preosteoclastic and bone
      endothelial cells: a juxtacrine model for migration and adhesion of osteoclast
      precursors.
AB  - The role of vascularization in the process of bone resorption has not been
      clarified. The interactions between vascular endothelium and osteoclast
      progenitors were analyzed using clonal cell lines of bone-derived endothelial and
      preosteoclastic cells. Insulin-like growth factor I is a major chemotactic
      stimulator of preosteoclastic cell migration mediated by bone endothelial cells.
      Osteoclast precursors rapidly adhered to bone endothelial monolayers. This
      phenomenon appeared to be cell-specific and mediated through the binding of
      vitronectin and fibronectin receptors to fibronectin. In addition, direct contact
      with bone endothelial cells induced osteoclast progenitors to differentiate into
      more mature elements, with the tendency to cluster together to form large
      multinucleated cells. These findings demonstrated specific in vitro interactions
      between bone endothelial cells and osteoclast progenitors, offering a new model
      for understanding the molecular mechanisms which direct the processes of
      osteoclast recruitment and ontogeny.

PMID- 7529771
TI  - Strategies for mapping and imitating viral B-cell epitopes.
AB  - Identification of viral B-cell epitopes is of importance in the selection of
      peptides for inclusion into subunit vaccines, the development of virus-specific
      serological tests and understanding the interaction of antibodies with viruses at
      a molecular level. B-cell epitopes can often be determined unequivocally by X-ray
      analyses of antibody-antigen complexes. This technique is, however, time
      consuming and alternative strategies have now been developed for identifying
      epitopes. This article provides an overview of approaches which are currently
      available for mapping and imitating B-cell epitopes.

PMID- 7529774
TI  - Nature and origin of cerebrovascular nerves with substance P immunoreactivity in
      bats (Mammalia: Microchiroptera), with special reference to species differences.
AB  - Double staining immunohistochemistry was used to investigate the origin and
      projection of nerves with substance P (SP) immunoreactivity (-IR) in the walls of
      the major cerebral arteries in two microchiropteran species. In the greater
      horseshoe bat, most of the cerebral perivascular nerves with SP-IR did not
      exhibit calcitonin gene-related peptide (CGRP)-IR, but emitted bright
      immunofluorescence for vasoactive intestinal polypeptide (VIP). In this species,
      a large number of cell bodies with both SP- and VIP-IR were observed in many
      cranial ganglia along various branches of the facial and glossopharyngeal nerves.
      There were no cell bodies immunoreactive for either SP and VIP in the two sensory
      (trigeminal and upper cervical dorsal root), two sympathetic (superior cervical
      and stellate), or two vagal (superior and jugular) ganglia. In addition, several
      thick fiber bundles with both SP- and VIP-IR were present in the wall of the
      cerebral carotid artery, and descended progressively reaching as far as the
      middle part of the basilar artery (BA). These and other findings suggest that SP
      immunoreactive nerves with VIP-IR but not CGRP-IR, which contribute to the rich
      innervation of the vertebrobasilar system in the greater horseshoe bat, originate
      from neurons with the same combination of peptide-IR in the major or local facial
      or glossopharyngeal parasympathetic ganglia, and enter the cranial cavity along
      the internal carotid artery. In the bent-winged bat, however, cerebral
      perivascular SP-immunoreactive nerves, as well as SP-immunoreactive neurons
      within the trigeminal and upper cervical dorsal root ganglia (uCDRG), showed
      neither CGRP-IR nor VIP-IR, and were mostly confined to the caudal BA and the
      vertebral artery (VA). These observations, in addition to the projection of this
      nerve type to the BA via the VA as fiber bundles, or through the meninges,
      indicate that the principal source of the cerebrovascular SP-immunoreactive
      innervation in this species is the uCDRG.

PMID- 7529770
TI  - Contribution of response kinetics to the response pattern: studies of responses
      to thyrotropin-releasing hormone in Xenopus oocytes.
AB  - In Xenopus oocytes injected with total rat pituitary GH3 cell RNA, thyrotropin
      releasing hormone (TRH) causes the activation of the inositol lipid transduction
      pathway and the induction of chloride conductance via calcium-activated channels
      (Oron et al., 1987, Mol. Endocrinol., 1:918-925). This response exhibits
      characteristic prolonged latency (Oron et al., 1988, Proc. Natl. Acad. Sci.
      U.S.A., 85:3820-3824; Lipinsky et al., 1993, Pflugers Arch., 425:140-149). We
      examined the role of agonist diffusion in the extracellular medium in the
      generation of latency and the determination of response amplitude. An increase in
      the viscosity of the medium markedly prolonged the latency and decreased the
      amplitude of the response. Moreover, an increase in the viscosity of the medium
      in the immediate vicinity of the oocyte had a major effect on both the latency
      and the amplitude of the response, which appeared to be a result of
      desensitization rather than restricted diffusion of chloride to the medium.
      Extrapolation to [TRH] infinity yielded a diffusion-dependent latency value of 0
      and a diffusion-independent latency value of 4 seconds. In low viscosity medium,
      at all TRH concentrations, diffusion contributed less than 2% to the latency of
      the response. This implied that events distal to ligand binding are responsible
      for a major part of latency. Analysis of the dependence of latency and amplitude
      of the response on [TRH] yielded Hill coefficients markedly smaller than unity,
      suggesting postreceptor negative modulation of the response. Preincubation of
      cells with a specific inhibitor of protein kinase C, chelerythrine, increased the
      Hill coefficients to unity and changed the shape of the Hill plot of response
      amplitudes. Our results suggest that at low agonist concentrations, even in a low
      viscosity medium, the prolonged latency allows negative effects on both latency
      and amplitude by a simultaneous activation of a protein kinase C.

PMID- 7529769
TI  - Activation of a transfected FGFR-1 receptor in Madin-Darby epithelial cells
      results in a reversible loss of epithelial properties.
AB  - Basic fibroblast growth factor (bFGF) is a potent mitogen for a wide variety of
      cell types derived from mesoderm and neuroectoderm. The activity of bFGF is
      mediated by several types of closely related receptors belonging to the tyrosine
      kinase family of receptors. We have found that Madin-Darby epithelial cells
      (MDCK) do not seem to produce bFGF or bFGF receptors. High level expression of
      human bFGF cDNA in these cells did not produce any mitogenic or morphological
      effects. Expression of the mouse-derived cDNA encoding FGF receptor-1 (FGFR-1) in
      MDCK cells resulted in the acquisition of a fibroblast-like morphology when the
      transfected cells were cultured at low density in the presence of 0.6% fetal calf
      serum and 20 ng/ml bFGF. Acidic fibroblast growth factor (aFGF) also induced
      these morphological changes but not keratinocyte growth factor. The morphological
      effect was not accompanied by increased bFGF-induced cell proliferation and did
      not result in the loss of epithelial cell markers such as cytokeratins. However,
      the morphological transition was accompanied by changes in the intracellular
      distribution of actin. In spite of these changes the transfected cells formed
      monolayers even in the presence of bFGF. Coexpression of bFGF and FGFR-1 in the
      MDCK cells resulted in similar morphological effects that were not dependent upon
      exogenous bFGF. These morphological effects were mimicked by exposure of MDCK
      cells to either orthovanadate or phorbol ester. Parental and FGFR-1-expressing
      MDCK cells formed monolayers that displayed high electrical resistance.
      Incubation of monolayers of FGFR-1-transfected cells with bFGF resulted in the
      loss of trans-epithelial resistance. Monolayers of parental MDCK cells did not
      lose their trans-epithelial resistance in response to bFGF, although exposure to
      phorbol ester did result in the loss of their trans-epithelial resistance,
      indicating that the effects on the trans-epithelial resistance are mediated by
      protein kinase C activation. Interestingly, orthovanadate did not cause a loss of
      transepithelial resistance, suggesting that the loss of trans-epithelial
      resistance is separable from the morphological transition.

PMID- 7529775
TI  - Local and commissural neuropeptide-containing projections of the nucleus of the
      solitary tract to the dorsal vagal complex in the pigeon.
AB  - The neuropeptide content of neurons of the nucleus of the solitary tract (NTS),
      which have local and commissural projections to the dorsal motor nucleus of the
      vagus (DMNX) and to NTS, were demonstrated in the pigeon (Columba livia) by using
      a combined fluorescein-bead retrograde-transport-immunofluorescence technique.
      The specific peptides studied were bombesin, cholecystokinin, enkephalin,
      galanin, neuropeptide Y, neurotensin, and substance P. Perikarya immunoreactive
      for bombesin were located in medial tier subnuclei of NTS and the caudal NTS.
      Most galanin- and substance P-immunoreactive cells were found in subnucleus
      medialis ventralis. Cells immunoreactive for neuropeptide Y were found in the
      medial tier of NTS and in the lateral tier, especially in subnucleus lateralis
      dorsalis intermedius. The majority of enkephalin- and neurotensin-immunoreactive
      cells were found centrally in subnuclei medialis dorsalis and medialis
      intermedius. Cells immunoreactive for cholecystokinin were located in subnuclei
      lateralis dorsalis pars anterior, medialis superficialis, and the caudal NTS.
      Based on the presence of retrogradely labeled cells, numerous neurons of the
      medial tier of NTS, but extremely few lateral tier NTS neurons, had projections
      to the ipsilateral and contralateral DMNX and NTS. The number of retrogradely
      labeled NTS cells was always greater ipsilaterally than contralaterally. The
      percentages of peptide-immunoreactive NTS cells that projected to the ipsilateral
      and contralateral DMNX were in the ranges of 29-61% and 10-48%, respectively. The
      percentages of peptide-immunoreactive NTS cells that projected to the
      contralateral NTS ranged from 13 to 60%. Peptide-immunoreactive NTS cells that
      have local and commissural projections to DMNX and NTS may act as interneurons in
      vagovagal reflex pathways and in the integration of visceral sensory and
      forebrain input to NTS and DMNX.

PMID- 7529776
TI  - Complexity and scaling properties of amacrine, ganglion, horizontal, and bipolar
      cells in the turtle retina.
AB  - In the present study we have evaluated the complexity and scaling properties of
      the morphology of retinal neurons using fractal dimension as a quantitative
      parameter. We examined a large number of cells from Pseudemys scripta and
      Mauremys caspica turtles that had been labeled using Golgi-impregnation
      techniques, intracellular injection of Lucifer Yellow followed by photooxidation,
      intracellular injection of rhodamine conjugated horseradish peroxidase, or
      intracellular injection of Lucifer Yellow or horseradish peroxidase alone. The
      fractal dimensions of two-dimensional projections of the cells were calculated
      using a box counting method. Discriminant analysis revealed fractal dimension to
      be a significant classification parameter among several other parameters
      typically used for placing turtle retinal neurons in different cell classes. The
      fractal dimension of amacrine cells was significantly correlated with dendritic
      field diameters, while the fractal dimensions of ganglion cells did not vary with
      dendritic field span. There were no significant differences between the same cell
      types in two different turtle species, or between the same types of neurons in
      the same species after labeling with different techniques. The application of
      fractal dimension, as a quantitative measure of complexity and scaling properties
      and as a classification criterion of neuronal types, appears to be useful and may
      have wide applicability to other parts of the central nervous system.

PMID- 7529778
TI  - Immunohistochemical techniques in Mohs micrographic surgery: their potential use
      in the detection of neoplastic cells masked by inflammation.
AB  - BACKGROUND: Histopathologic evaluation of tissue obtained from Mohs micrographic
      surgery is the key step in obtaining complete tumor removal. Residual undetected
      tumor may result in recurrence. OBJECTIVE: In circumstances in which the
      histopathologic interpretation is difficult, we assessed the potential use of
      immunohistochemical techniques to detect tumor in Mohs micrographic surgical
      specimens. METHODS: A rapid immunoperoxidase technique with monoclonal
      anticytokeratin antibodies was performed on Mohs frozen sections. Cases selected
      included morpheaform basal cell carcinomas, perineural tumors, and sections with
      dense inflammation without apparent tumor. RESULTS: Four cases are described as
      examples that highlight the potential usefulness of immunostaining of Mohs tissue
      sections. Anticytokeratin antibodies helped to confirm free tumor margins, thus
      avoiding the unnecessary sacrifice of normal tissue, and to delineate tumor not
      identified in hematoxylin and eosin frozen sections. CONCLUSION:
      Immunohistochemical staining of Mohs micrographic surgical specimens with
      anticytokeratin antibodies is particularly useful when dense inflammatory
      infiltrate is present, because the latter may obscure any residual tumor.
      Application of this technique to difficult cases may prevent tumor recurrences or
      unnecessary excision of normal tissue.

PMID- 7529777
TI  - Detection of circulating adhesion molecules in erythrodermic skin disease.
AB  - BACKGROUND: Diagnosis of the underlying dermatosis in erythroderma is often
      difficult. The cause of increased mortality in erythroderma, particularly in
      relation to infection, is incompletely understood. OBJECTIVE: We investigated the
      potential diagnostic use of circulating intercellular adhesion molecule-1 (cICAM
      1), vascular cell adhesion molecule-1 (cVCAM-1), and E-selectin (cE-selectin)
      levels in erythroderma. METHODS: cICAM-1, cVCAM-1, and cE-selectin were measured
      by enzyme-linked immunosorbent assay in 14 patients with erythroderma of known
      cause and in 17 control subjects. Levels were correlated with other markers of
      the inflammatory response. RESULTS: In erythroderma median cICAM-1, cVCAM-1, and
      cE-selectin levels were significantly elevated, but no difference was found
      between values in patients with eczema and values in those with psoriasis.
      Circulating adhesion molecule levels did not correlate with erythrocyte
      sedimentation rate or total white blood cell count. CONCLUSION: cICAM-1, cVCAM-1,
      and cE-selectin were detectable in patients with erythroderma but were not
      differential diagnostic use in this study. Because in vitro these molecules may
      interfere with normal cell adhesion mechanisms, we speculate that they may
      contribute to the immunosuppressive state in these patients.

PMID- 7529779
TI  - Guidelines of care for actinic keratoses. Committee on Guidelines of Care.

PMID- 7529780
TI  - Identification of "premyelination" by diffusion-weighted MRI.
AB  - OBJECTIVE: The purpose of this study was to compare white matter maturation as
      demonstrated with diffusion-weighted MRI and with myelin-sensitive histological
      staining. MATERIALS AND METHODS: The diffusion-, T1-, and T2-weighted SE MRI at
      4.7 T was performed weekly in a total of 16 rat pups, aged from 5 days to 8
      weeks, 2 animals evaluated per week. Heavily diffusion-weighted sequences were
      obtained with the diffusion-sensitizing gradient switched alternately in two
      orthogonal directions. To enhance signal intensity of anisotropic structures, a
      synthesized image (referred to as the "anisotropy index map") was constructed
      from the ratio of pairs of images acquired with diffusion sensitization of
      identical magnitude but orthogonal direction sensitivity. The anisotropy index
      maps were used for comparison with T1-weighted and heavily T2-weighted SE
      sequences and histological sections, respectively. RESULTS: The first evidence of
      diffusion anisotropy on anisotropy index maps preceded initial myelin as well as
      neurofibril staining by 5-12 days and T2 shortening by 2 weeks. The T1-weighted
      sequences did not yield visible changes and were not helpful for the assessment
      of ongoing white matter maturation in this model. CONCLUSION: Magnetic resonance
      imaging signal intensity changes based on anisotropic water diffusion were
      demonstrated in regions of unmyelinated cerebral white matter tracts of albino
      rat pups before the onset of histologically detectable myelin. The ability of in
      vivo mapping of premyelinating white matter maturation indicates a new diagnostic
      use of MRI in evaluating cerebral white matter maturation.

PMID- 7529781
TI  - Anaphylactic reaction to local administration of rifamycin SV.
AB  - BACKGROUND AND OBJECTIVE: Systemic reactions during anesthesia are commonly
      attributed to muscle relaxants, hypnotics, macromolecular solutions, latex, or
      parenteral antibiotics. After exclusion of these different components as causes,
      we were interested in the potential implication of rifamycin in the systemic
      reaction, which occurred during anesthesia, and in the immunologic mechanism by
      which it can trigger this reaction. METHODS: We report four cases of systemic
      reactions occurring after local administration of rifamycin. Three patients
      needed orthopedic surgery, and the fourth needed a urethrotomy. Severe systemic
      reactions occurred in all four patients when the surgeon washed the incision area
      with a rifamycin solution. All patients correctly responded to appropriate
      treatment and recovered. Skin tests were performed 2 months after the incident
      with the drugs used during anesthesia, latex, and rifamycin. To assess the
      relationship with a possible IgE-mediated mechanism, two in vitro tests were
      concomitantly performed to evaluate the cell reactivity to rifamycin: (1)
      determination of histamine release from peripheral basophils and (2) platelet
      cytotoxicity test, which explored the presence on platelets of specific IgE
      antibodies bound to the low-affinity receptor for IgE. RESULTS: Skin tests were
      performed with different drugs used during surgery, and results were only
      positive for rifamycin in the four cases, accompanied in two cases by a systemic
      reaction. Histamine release from basophils was positive in three of four
      patients. The platelet cytotoxicity test results were positive in all four cases.
      CONCLUSION: It appears that rifamycin, used locally during surgery, is apt to
      trigger severe systemic anaphylactic reactions, which are linked to an IgE
      related process. This situation is worth pointing out, especially in patients who
      undergo repeated orthopedic operations during which, at least in Europe,
      rifamycin is commonly used for the prevention of local sepsis.

PMID- 7529782
TI  - Enhanced human IgE production results from exposure to the aromatic hydrocarbons
      from diesel exhaust: direct effects on B-cell IgE production.
AB  - Epidemiologic and experimental studies suggest that air pollution, and
      particularly diesel exhaust particles (DEPs) may play a role in the increasing
      prevalence and severity of airway allergic disease. We show that the extract of
      polyaromatic hydrocarbons (PAHs) from DEPs (PAH-DEP) enhances human IgE
      production from purified B cells. Interleukin-4 plus CD40 monoclonal antibody
      stimulated IgE production was enhanced 20% to 360% by the addition of PAH-DEP
      over a period of 10 to 14 days. This effect was increased when PAH-DEP was added
      2 to 5 days after cultures were initiated. PAH-DEP itself did not induce IgE
      production or synergize with interleukin-4 alone to induce IgE from purified B
      cells, suggesting that it was enhancing ongoing IgE production rather than
      inducing germline transcription or isotype switching. The prototype
      nonmetabolized aromatic hydrocarbon 2,3,7,8 tetracholorodibenzo-p-dioxin, which
      functions solely through activation of the cytosolic aromatic hydrocarbon
      receptor complex, also increased IgE production. Additionally, the pattern of
      mRNAs coding for distinct isoforms of the epsilon chain was altered by PAH-DEP,
      and B-cell expression of the low-affinity IgE receptor was upregulated by PAH
      DEP. Enhanced IgE production in the human airway, resulting from exposure to PAH
      DEP, may be an important factor in the increase in airway allergic disease.

PMID- 7529783
TI  - The relationship between joint hypermobility and neurodevelopmental attributes in
      elementary school children.
AB  - Joint hypermobility is associated with motor developmental delay in infancy. To
      assess this finding in school-aged children, 320 first- and second-grade
      elementary school children and 110 children attending a special education program
      were assessed. Joint hypermobility was found in 40 (12.4%) and seven (6.4%) of
      the children attending the regular and special education classes, respectively.
      No difference in the neurologic status or verbal and eye-hand coordination task
      performance was found between the children of the study group and their age- and
      sex-matched controls. It appears that joint hypermobility and neurodevelopmental
      dysfunctions are not causally related and have a different maturational course.

PMID- 7529784
TI  - Antigen unmasking for immunoelectron microscopy: labeling is improved by treating
      with sodium ethoxide or sodium metaperiodate, then heating on retrieval medium.
AB  - To optimize the ultrastructural localization of immunoglobulin G in corneal
      crystalloid deposits, we compared a range of antigen unmasking techniques. A
      human corneal biopsy specimen was fixed in formalin, post-osmicated, and embedded
      in epoxy resin for electron microscopy. Thin sections were immunogold-labeled for
      IgG after treatment with sodium ethoxide or sodium metaperiodate. Sections were
      also treated by heating them at 95 degrees C while they floated on water, 0.01 M
      citrate buffer (pH 6.0), or sodium metaperiodate. The treatments were applied
      separately and combined. After labeling, crystalloids in untreated sections had a
      probe density of 5 particles/microns2. Crystalloids in sections treated only with
      sodium ethoxide or sodium metaperiodate had probe densities of 15-20
      particles/microns2. Sodium ethoxide combined with heating on water, or citrate
      buffer, gave probe densities of 140-160 particles/microns2. Sodium metaperiodate
      combined with heating on citrate buffer gave the highest probe density (195
      particles/microns2). Although sodium ethoxide coupled with heating increased
      probe density, the ethoxide etched the sections and caused unacceptable damage.
      Treatment with sodium metaperiodate followed by heating on citrate buffer is
      recommended for antigen unmasking. This combination gave a high probe density and
      sections remained intact, with good ultrastructural detail.

PMID- 7529785
TI  - Expression of proteoglycans and hyaluronan during wound healing.
AB  - We investigated the expression of proteoglycans (PGs) and hyaluronan (HA) during
      healing of human mucosal wounds. Biopsy specimens of experimental wounds were
      taken 1, 3, and 7 days after wounding. Frozen sections were used for
      immunolocalization of CD44, syndecan-1, basement membrane-associated heparan
      sulfate proteoglycan (BM-HSPG), decorin, and biglycan. HA was localized in
      paraffin sections with a specific HA-binding probe. Epithelium showed first signs
      of migration on Day 1, more progressive migration on Day 3, and epithelial sheets
      confronted on Day 7. CD44 surrounded migrating keratinocytes at all stages of
      wound healing. In epithelium, CD44 and HA remarkably localized to the same
      region. Expression of syndecan-1 was switched from the suprabasal cell layer of
      unwounded epithelium to the basal cell layer of the migrating wound epithelium.
      BM-HSPG was absent under migrating keratinocytes. It started to reappear at the
      basement membrane zone on Day 7. The area under the wound epithelium containing
      newly synthesized collagen fibers first became positive for decorin on Day 7,
      whereas staining of biglycan was negative. Granulation tissue was also strongly
      positive for CD44 and hyaluronan. Our results indicate that migrating
      keratinocytes express both CD44 and syndecan-1 but not BM-HSPG. During
      differentiation of keratinocytes, expression of CD44 preceded that of syndecan-1.
      The results suggest that different HSPGs have multiple functions in keratinocyte
      migration and differentiation during reepithelialization.

PMID- 7529786
TI  - Odontoblast processes in dentin revealed by fluorescent Di-I.
AB  - There has been controversy about the length and structure of the odontoblast
      process within dentin since the earliest histologic studies of teeth. Our
      objective was to use the fluorescent carbocyanine dye Di-I combined with a new
      gelatin embedment procedure and confocal microscopy to determine the structure
      and extent of odontoblast processes in developing and mature rat teeth, injured
      rat molars, reparative dentin, and adult monkey teeth. We found that odontoblast
      processes do not extend into outer dentin or to the dentin-enamel junction except
      during early stages of development. Those in innervated regions of crown are long
      and straight, whereas those in roots are extensively branched and shorter. Cavity
      injury to crown dentin caused odontoblast fragments to be aspirated into outer
      dentin. In reparative dentin the odontoblast processes were branched and similar
      to those in roots. We used photoconversion and electron microscopy to show that
      Di-I fills the entire odontoblast after gelatin embedment, including the
      cytoplasm. This is a different type of carbocyanine staining from any previously
      reported, and it also stains other cells in adjacent hard tissues such as bone
      and cementum. The Di-I-gelatin method is a new way to use carbocyanine dyes. It
      has enabled us to solve a long-standing controversy about the histology of teeth,
      and it should be useful for many other studies of cell structure.

PMID- 7529787
TI  - Resolution of DNA damage at the single-cell level shows largely different actions
      of X-rays and bleomycin.
AB  - Both X-rays and the radiomimetic agent bleomycin (BLM) induce DNA strand breaks,
      predominantly via reactive radicals. To compare the induction of breaks with the
      two agents in Chinese hamster (CHO-K1) cells, two different alkaline unwinding
      methods, a 3H tracer-based analysis of large cell populations and an optical
      adaption allowing measurement of single cells, were applied. Radiation and BLM
      show qualitatively similar dose responses when the average number of DNA strand
      breaks is measured in a large cell population. However, the breakage pattern at
      the single-cell level indicates large discrepancies between the actions of the
      two agents. Irradiated cells show a uniform distribution of DNA strand breaks
      over the cell population. Effects of treatment with 30 micrograms x ml-1 BLM for
      2 hr vary from practically zero in some cells to high levels of DNA strand
      breakage in others. Unlike the repair of radiation-induced DNA breaks, the repair
      efficiency of BLM-induced DNA strand breaks, as measured at the single-cell
      level, varies strongly among cells of the same population. Such heterogeneity at
      the cellular level potentially reduces BLM's usefulness for tumor therapy because
      the appearance of BLM-resistant subpopulations may critically impair treatment
      outcome.

PMID- 7529788
TI  - Staphylococcal enterotoxin B activates purified NK cells to secrete IFN-gamma but
      requires T lymphocytes to augment NK cytotoxicity.
AB  - Staphylococcal enterotoxin B (SEB) is known for its effects on T lymphocytes; the
      mechanism of this activation is well studied. Although it is anticipated that
      there would be effects on other cells in the milieu, the mechanisms of activation
      of non-T immune cells are not well understood. This report examines the effects
      of SEB on human NK cells. Incubation of PBMC with SEB augmented NK cytotoxicity
      against the NK-sensitive targets K562 and Molt-4 and induced activity against the
      NK-resistant targets, Mel-30 and Raji. The degree of superantigen-augmented
      killer (SAK) activity induced by the SEB treatment correlated with the
      concentration of the superantigen in the mixture. Specific neutralizing Abs for
      lymphokines or monokines added to cultures showed that IL-2, IFN-gamma, or IL-12
      each participated in the phenomenon; addition of all Abs together blocked most,
      but not all, SAK activity. Highly purified T lymphocytes (but not monocytes)
      supported the development of SAK activity in enriched cultures of CD56+ cells.
      The SAK activity was blocked by specific Abs to IL-2 and IFN-gamma in cocultures
      of T cells and CD56+ cells. In addition, SEB induced IFN-gamma secretion from
      sorted CD56+ cells. These data show for the first time that superantigen directly
      initiated cytokine synthesis in NK cells, and that SAK activity was induced as a
      consequence of products secreted from activated T lymphocytes. Such a
      superantigen effect on NK cells would place the NK lymphocyte in a pivotal role
      in determining the outcome of infection or immunopathology caused by superantigen
      exposure.

PMID- 7529789
TI  - Expression of VCAM-1 (CD106) by a subset of TCR gamma delta-bearing lymphocyte
      clones. Involvement of a metalloprotease in the specific hydrolytic release of
      the soluble isoform.
AB  - The cytokine-inducible vascular cell adhesion molecule 1/CD106 is widely
      distributed in endothelial, epithelial, macrophage, and dentritic cells. We
      previously have reported a mAb termed sTA that recognizes the CD106 molecule on
      various TCR gamma delta T cell clones that do not proliferate in response to an
      anti-CD3 stimulation. In the present report, further biochemical analysis reveals
      two intracellular precursors (82 and 98 kDa) of the membrane-bound 110-kDa form
      of CD106. In addition, we detect a 100-kDa soluble form in the culture
      supernatant of the specific cloned lymphocytes. Phorbol ester raises the amount
      of the soluble CD106 in the supernatant while simultaneously inducing the
      disappearance of the membrane-bound form. We show that the membrane-anchored form
      of CD106 is converted to soluble form by a regulated proteolytic cleavage process
      involving a metalloprotease. EDTA and 1,10-phenanthroline, two potent inhibitors
      of metalloproteases, specifically inhibit the conversion of the membrane anchored
      to the soluble form of the CD106 molecule. In fact, these results implicate a
      Zn(2+)-activated metalloprotease in the regulation of CD106 expression in a
      subset of T cells and, therefore, represent a novel pathway of T cell functions.

PMID- 7529790
TI  - Expression of vitronectin receptor on human NK cells and its role in protein
      phosphorylation, cytokine production, and cell proliferation.
AB  - In this paper, we provide evidence that the vitronectin receptor (VNR) alpha v
      beta 3 is expressed on human NK cells. The presence of this VNR on freshly
      purified NK cells was demonstrated by flow cytometry analysis, as well as
      biochemically, after 125I-labeled surface lactoperoxidase labeling and
      immunoprecipitation. mAbs LM142 and LM609 specific for alpha v and alpha v beta
      3, respectively, precipitated a heterodimer of alpha- and beta-chains with
      approximate molecular masses of 155 and 110 kDa under nonreducing conditions.
      Under reducing conditions, there was an apparent decrease in the molecular mass
      of the alpha-chain, which is likely to result from the release of a protein of 20
      to 30 kDa linked by internal disulfide bond to the alpha v-chain. Integrin alpha
      v beta 3 expressed on NK cells became functional, i.e., was able to bind its
      ligand, vitronectin (VN), only after cellular activation or when costimulation
      with an additional signal was provided. Thus, NK cells adhered to plastic
      immobilized VN only after IL-2 activation, and RGD-containing synthetic peptides
      or mAbs specific for alpha v beta 3 complex inhibited this binding. To assess the
      role of the VNR in signal transduction, anti-beta 3 mAb was used to cluster the
      VNR on NK cells and, thereby, mimic the process that occurs during formation of
      adhesive contacts. Cross-linking of VNR on fresh NK cells stimulated
      phosphorylation on tyrosine residues of several intracellular proteins. The major
      increase in tyrosine phosphorylation was observed in proteins of approximate
      molecular masses of 75 and 120 kDa. Therefore, signal transduction by the VNR on
      NK cells induced activation of intracellular protein kinases. Ligand engagement
      of the VNR on NK cells also costimulated cytokine production and proliferation of
      NK cells. Binding of NK cells to plastic-immobilized VN served as a costimulus
      with either anti-Fc gamma RIII or IL-2 to produce IFN-gamma, TNF-alpha, and cell
      proliferation. Our findings suggest that occupancy and subsequent clustering of
      VNRs play a role in the activation and function of human NK cells.

PMID- 7529791
TI  - MHC class I signaling in T cells leads to tyrosine kinase activity and PLC-gamma
      1 phosphorylation.
AB  - We have studied the biochemical signal pathway leading to a rise in intracellular
      free calcium concentration ([Ca2+]i) following cross-linking of MHC class I (MHC
      I) molecules on human T leukemic Jurkat cells. Evidence is presented that MHC-I
      signaling is dependent on tyrosine kinase activity before the observed increase
      in [Ca2+]i. Thus, tyrosine phosphorylation was detected within 5 s after MHC-I
      cross-linking, whereas an increase in [Ca2+]i was observed after a lag period of
      30 s. Moreover, an inhibitor of tyrosine kinases, herbimycin A, almost completely
      blocked MHC-I-induced tyrosine phosphorylation and the subsequent calcium
      response. The early tyrosine kinase activity was found to be dependent on
      expression of the TCR/CD3 complex and the CD45 molecule on the surface of the T
      cells. Furthermore, MHC-I cross-linking was shown to tyrosine phosphorylate PLC
      gamma 1 (phospholipase C-gamma 1). Collectively, these results indicate that the
      MHC-I signaling pathway is linked to activation of tyrosine kinase(s) in Jurkat
      cells.

PMID- 7529793
TI  - Peptide-induced rescue of serologic epitopes on class I MHC molecules.
AB  - To monitor conformational changes in MHC class I structure induced by interaction
      with peptide or beta 2-microglobulin (beta 2-m), we have taken a serologic
      approach. Previous studies by us and others have defined circumstances wherein
      specific peptides can decrease serologic recognition of class I molecules.
      However, such blocking of serologic epitopes has often been interpreted as steric
      hindrance by peptide side chains. In this paper, we describe peptide-induced
      gains in recognition by mAbs 30-5-7, 34-1-2, and B22/249. In experiments with mAb
      30-5-7, impaired reactivity, which resulted from an Ld loop mutation, was
      specifically rescued by the binding of a beta-galactosidase-derived peptide to
      the Ld mutant. In studies with mAb 34-1-2, poor Ld detection was enhanced by
      mutations in Ld at beta 2-m interaction sites or by changes within the peptide
      binding groove. To evaluate whether known peptides in the Ld groove could
      influence 34-1-2 recognition, we tested six peptide ligands, four of which
      increased the reactivity of 34-1-2 with the Ld-expressing cell to various degrees
      (up to 14-fold). It is of interest that Ld mutations at position 9 and 95/97 made
      significant differences in the ranking of the peptides in regard to their ability
      to increase recognition by 34-1-2 and B22/249. This finding suggests that
      mutations in the binding groove can alter peptide conformation and result in
      secondary changes in class I structure. On the basis of the cumulative serologic
      data, we propose that the class I molecule displays considerable fluidity, and is
      structurally influenced by both beta 2-m and peptide.

PMID- 7529794
TI  - Comitogenic effects of very late activation antigens on CD3-stimulated human
      thymocytes. Involvement of various tyrosine kinase pathways.
AB  - Thymocytes display several integrins that are involved in cell-extracellular
      matrix interactions and differentiation processes. We have examined the role of
      very late activation Ag (VLA) on human thymocyte stimulation. VLA-4, VLA-5, and
      VLA-6 activated with either mAbs or their natural ligands (fibronectin, laminin,
      and vascular cell adhesion molecule-1) are able to transduce costimulatory
      signals in thymocytes activated via the CD3 pathway, i.e., enhancement of
      thymocyte proliferation, CD25 and CD69 expression, and IL-2 secretion. In
      contrast, activation of thymocytes with a mitogenic pair of CD2 mAb was not
      modified by VLA molecules. Cross-linking of both beta 1- and alpha 5-chains
      induced tyrosine phosphorylation of several proteins, whereas the cross-linking
      of the alpha 4- and alpha 6-chains did not. Moreover, a different pattern of
      tyrosine phosphorylation was observed when thymocytes were activated via either
      beta 1- or alpha 5-chains. These results suggest that VLA molecules activate
      tyrosine kinase pathways in thymocytes, and that different pathways would be
      implicated during thymocyte interactions with extracellular matrix or accessory
      cells, which are likely to play a role in thymocyte differentiation.

PMID- 7529792
TI  - Multivalent, but not divalent, antigen receptor cross-linkers synergize with CD40
      ligand for induction of Ig synthesis and class switching in normal murine B
      cells. A redefinition of the TI-2 vs T cell-dependent antigen dichotomy.
AB  - A number of previous studies have suggested that cross-linkage of the B cell Ag
      receptor may be critical for induction of humoral immune responses to T cell
      dependent (TD) Ags in vivo. Previous work also indicated a critical role, in
      these responses, for CD40-mediated signaling mediated by binding of the inducible
      T cell membrane protein, CD40 ligand (CD40L). Data in this manuscript demonstrate
      that concentrations of bivalent anti-IgD or anti-IgM Ab as high as 30
      micrograms/ml induced little if any enhancement of CD40-dependent Ig secretion by
      resting murine B cells. In contrast, concentrations as low as 3 pg/ml of
      multivalent, dextran-conjugated, anti-IgD (alpha delta-dex) or anti-IgM (alpha mu
      dex) were strongly synergistic with CD40L for induction of B cell proliferation,
      viable cell outgrowth, Ig isotype switching, and maturation to Ig secretion. As
      many as 30% of the B cells became membrane IgG1+ after stimulation with CD40L,
      anti-Ig-dextran, and IL-4 + IL-5, with a concomitant three- to fivefold increase
      in numbers of viable cells as compared with control cultures. High Ig secretory
      responses were obtained in response to the combined actions of CD40L and alpha
      delta-dex or alpha mu-dex, utilizing concentrations of B cell activator that when
      acting alone induced only modest Ig secretion. Surprisingly, although we
      previously demonstrated that alpha delta-dex selectively and strongly suppressed
      IgE production by T cell-activated B cells, it strikingly augmented IgE
      expression by CD40L-activated B cells. These data suggest 1) a key role for Ag
      receptor cross-linkage in CD40-dependent induction of humoral immune responses,
      2) that to achieve a membrane Ig-dependent enhancing effect in the presence of
      activated T cells, TD Ags must be displayed to the B cell as a multivalent array
      of epitopes, 3) that picomolar concentrations of Ag can mediate this effect, and
      4) that at least for induction of IgE responses, B cell stimulation via CD40L or
      via activated T cells may lead to a qualitatively different pathway of
      activation.

PMID- 7529795
TI  - Analysis of an initial step of T cell adhesion to endothelial monolayers under
      flow conditions.
AB  - We analyzed an initial step of T cell adhesion to endothelial cells under flow
      conditions. An initial step in T cell-endothelial cell interactions was
      characterized either by a rolling phase, or by an immediate arrest without
      rolling. Anti-E- and P-selectin Abs inhibited T cell rolling on endothelial cells
      under flow conditions. The rolling velocity of T cells on endothelial cells
      increased after treatment of endothelial cells with anti-E- or P-selectin Abs.
      Also, rolling of T cells was observed on E-selectin-transfected CHO cells but not
      on ICAM-1-transfected CHO cells. Thus, rolling of T cells under flow condition
      was dependent on E-selectin as well as P-selectin expressed on endothelial cells.
      In contrast, neither anti-E- nor P-selectin Abs inhibited the immediate arrest of
      T cells on endothelial cells significantly and anti-ICAM-1 Abs also failed to
      inhibit the immediate arrest of T cells. Therefore, other adhesion molecules may
      play an important role in the immediate arrest of T cells under flow conditions.
      The number of CD45RA- T cells rolling on E-selectin-transfected CHO cells was
      much higher than that of CD45RA+ T cells.

PMID- 7529796
TI  - Antigen receptor cross-linking differentially regulates germ-line CH ribonucleic
      acid expression in murine B cells.
AB  - Cytokines are believed to regulate Ig class switching, in part, through selective
      modulation of germ-line constant heavy (CH) gene transcription. B cell activators
      such as LPS or activated T cell membranes also influence germ-line CH RNA
      expression in the absence of exogenous cytokines. In this report we determined
      whether multivalent Ag receptor cross-linking, utilizing dextran-conjugated anti
      IgD Abs (alpha delta-dex), could also regulate germ-line CH RNA expression. We
      demonstrated that alpha delta-dex markedly inhibited germ-line epsilon RNA
      expression, but strongly augmented germ-line gamma 1 RNA, in LPS + IL-4
      stimulated cultures. This was correlated with > 90% alpha delta-dex-mediated
      suppression in the secretion of IgE and generation of membrane (m)IgE+ cells, and
      a more modest 50% reduction in IgG1 synthesis and mIgG1+ cells. Furthermore,
      alpha delta-dex inhibited the LPS induction of both gamma 3 and gamma 2b germ
      line RNA and the associated secretion of IgG3 and IgG2b. A similar alpha delta
      dex-mediated suppression of germ-line gamma 2a RNA and IgG2a secretion in LPS +
      IFN-gamma-stimulated cultures was observed. By contrast, activation of resting B
      cells with alpha delta-dex alone led to induction of germ-line gamma 3, gamma 1,
      and gamma 2b RNA but did not stimulate detectable expression of RNA specific for
      gamma 2a or epsilon. These studies demonstrate that: 1) germ-line gamma 1 gene
      expression is regulated uniquely, 2) germ-line transcription and switch
      recombination can be dissociated, 3) the germ-line transcription of each IgG
      isotype has an independent pattern of regulation, and 4) cross-linking of the Ag
      receptor, by itself, can stimulate small amounts of germ-line CH RNA.

PMID- 7529797
TI  - Characterization of epitopes recognized by hapten-specific CD4+ T cells.
AB  - Although protein-derived nominal Ags have, in many instances, been precisely
      determined, the epitopes recognized by hapten-specific CD4+ T cells responsible
      for contact sensitization have not been defined. To better understand the nature
      of the precise epitopes generated after hapten interaction with Langerhans cells
      (LC), we assessed the ability of TNP-modified I-Ak- and I-Au-binding peptides to
      activate hapten-specific CD4+ T cells obtained respectively from TNCB-primed C3H
      (H-2k) and PL/j (H-2u) mice. Using LC as APC, I-Ak-restricted TNP-specific CD4+ T
      cells proliferated in the presence of the synthetic peptide hen egg lysozyme 52
      61 derivatized with TNP at position 56, and less so when TNP was coupled at
      positions 53 or 59. Similarly, I-Au-restricted TNP-specific CD4+ T cells from
      PL/j mice were triggered by the synthetic I-Au-binding 13 mer poly(A)-Y5-R6 TNP
      modified at position 4, and to a limited extent with TNP coupled in positions 7
      or 10. Our results indicate that hapten-modified MHC class II binding
      nonautologous peptides are recognized by hapten-specific CD4+ T cells and that
      precise positioning of hapten molecules on peptides binding MHC class II
      molecules is required for optimal CD4+ T cell recognition. These findings provide
      insight into the manner in which haptens are recognized by T cells involved in
      contact sensitivity and should facilitate the study and design of specific
      therapies for the manipulation of hapten-specific CD4+ T cell responses.

PMID- 7529798
TI  - Characterization of human Fas gene. Exon/intron organization and promoter region.
AB  - Ligation of the Fas cell-surface molecule induces apoptosis. Defective Fas
      mediated apoptosis has been associated with spontaneous autoimmunity in mice.
      Using human Fas/Apo-1 cDNA as a probe, we have molecularly cloned and
      characterized the human Fas chromosomal gene. The gene consists of nine exons and
      spans more than 26 kilobases of DNA. The lengths of introns vary from > 14
      kilobases at the 5' end of the gene to 152 base pairs upstream of the exon
      encoding the transmembrane domain. The domain structure of the human Fas is
      encoded by an exon or a set of exons. Primer extension analysis revealed three
      major transcription initiation sites. The promoter region lacked canonical "TATA"
      and "CAAT" boxes but was a "GC-rich" sequence, and contained consensus sequences
      for AP-1, GF-1, NY-Y, CP-2, EBP20, and c-myb. These data provide the first
      characterization of the human Fas gene and insight into its regulatory region.

PMID- 7529799
TI  - Dengue virus-specific, HLA-B35-restricted, human CD8+ cytotoxic T lymphocyte
      (CTL) clones. Recognition of NS3 amino acids 500 to 508 by CTL clones of two
      different serotype specificities.
AB  - Dengue virus infections are a major cause of morbidity and mortality in tropical
      and subtropical areas of the world. We analyzed dengue virus-specific CD8+ CD4-
      CTL at the clonal level to further understand the role of CD8+ CTL in dengue
      virus infections. Dengue virus-specific CD8+ CTL clones were established from
      lymphocytes of a dengue 4-immune adult. Three patterns of dengue serotype
      specificities were identified: 1) specific for dengue 4, 2) cross-reactive for
      dengue 2 and dengue 4 (subcomplex-specific); and 3) cross-reactive for all four
      dengue virus serotypes. Three dengue 4-specific clones and one dengue 2/dengue 4
      cross-reactive clone were further analyzed. All four of the clones were HLA-B35
      restricted and recognized NS3. The epitopes were mapped to amino acids (aa) 483
      to 618 of NS3. The epitope was then defined by using synthetic peptides. Three
      dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone
      recognized the same peptide (TPEGIIPTL) encompassing aa 500 to 508 of dengue 4
      NS3. The peptide encompassing aa 500-508 of dengue 2 NS3 was recognized by a
      dengue 2/dengue 4 cross-reactive clone but was not recognized by the dengue 4
      specific clones. Dengue 4-specific and dengue 2/dengue 4 cross-reactive clones
      used different TCR. These results indicate that CD8+ CTL clones that use
      different TCR and demonstrate two distinct serotype specificities recognize the
      same 9-mer peptide in the context of HLA-B35.

PMID- 7529801
TI  - Compartmentalized roles for leukocytic adhesion molecules in lung inflammatory
      injury.
AB  - By using the model of acute injury caused by intrapulmonary deposition of IgG
      immune complexes, blocking mAb to CD11a, CD11b, L-selectin, and intercellular
      adhesion molecule-1 (ICAM-1) were administered either i.v. or intratracheally
      (i.t.). The effects of these interventions were assessed according to lung
      injury, lung content of myeloperoxidase (MPO), TNF-alpha, and cellular content in
      bronchoalveolar lavage (BAL) fluids, and up-regulation of pulmonary vascular ICAM
      1. In animals treated i.v. with Abs to CD11a, L-selectin, or ICAM-1 lung injury
      was significantly attenuated in parallel with reduced lung content of MPO. Under
      similar conditions, treatment with anti-CD11b had no effect. However, when the
      same mAb were administered i.t., anti-CD11a and anti-L-selectin were without
      protective effects, whereas i.t. administered anti-CD11b and anti-ICAM-1 were
      each highly protective. The protective effects of anti-CD11b were related to
      profound reductions in BAL levels of TNF-alpha, pulmonary vascular up-regulation
      of ICAM-1, and lung content of MPO. The protective effects of i.t.-administered
      anti-ICAM-1 were not associated with reduced BAL levels of TNF-alpha. Protective
      effects of mAb were also reflected in reductions of retrievable neutrophils in
      BAL fluids. mAb to rat CD11b and CD18 but not to rat CD11a suppressed in vitro
      production of TNF-alpha by immune complex-stimulated rat alveolar macrophages.
      The mAb did not reduce NO2-/NO3- generation in stimulated macrophages but all mAb
      (except anti-ICAM-1) reduced O2- responses in macrophages. These data suggest a
      compartmentalized role for adhesion molecules in lung inflammatory injury after
      intraalveolar deposition of IgG immune complexes, with CD11a, L-selectin, and
      ICAM-1 being important in the vascular compartment for neutrophil recruitment,
      whereas in the alveolar compartment CD11b and ICAM-1 (but not CD11a and L
      selectin) seem to play key roles.

PMID- 7529800
TI  - Chemotactic agonists induce cytokine generation in eosinophils.
AB  - Recent studies have shown that eosinophils are capable of generating and
      releasing cytokines, providing a novel biologic aspect of eosinophils for
      regulating allergic inflammation by an autocrine or paracrine mechanism.
      Eosinophils synthesize various cytokines; however, the physiologic stimuli that
      trigger eosinophils to generate cytokines have not been fully elucidated. We
      examined the effect of chemotactic agonists on eosinophil cytokine generation by
      employing the determination of IL-8 as the main parameter. Both C5a and FMLP
      stimulated eosinophils to release IL-8, whereas platelet-activating factor and C
      C chemokines did not exert any significant effects. On a molar basis, C5a was two
      orders of magnitude more potent than FMLP. The generation of IL-8 by
      chemoattractants was absolutely dependent on the presence of cytochalasin B.
      Pertussis toxin completely attenuated C5a- and FMLP-induced IL-8 production,
      indicating the involvement of pertussis toxin-sensitive G-proteins in the signal
      transduction process leading to these responses. Experiments of in situ
      hybridization and PCR amplification revealed that both C5a and FMLP promoted
      eosinophil IL-8 production through transcriptional gene activation. Pyrrolidine
      dithiocarbamate completely abrogated chemoattractant-induced IL-8 production,
      indicating the involvement of NF-kappa B in the cytoplasmic/nuclear signal
      transduction process. Furthermore, chemoattractant-induced cytokine production
      was not limited to IL-8; C5a and FMLP but not platelet-activating factor induced
      significant secretion of granulocyte-macrophage-CSF from eosinophils. These
      results indicate that C5a and FMLP stimulate eosinophils to elaborate cytokines,
      which could be an important mechanism in the regulation of allergic inflammation.

PMID- 7529802
TI  - Endothelial cell associated platelet-activating factor (PAF), a costimulatory
      intermediate in TNF-alpha-induced H2O2 release by adherent neutrophil leukocytes.
AB  - TNF is a strong secretagogue for surface-contacting neutrophils. During
      inflammation, endothelium offers the first substrate for neutrophil adherence and
      for modulation of the toxic response of neutrophils to soluble agonists such as
      TNF. In this in vitro study, evidence is presented that endothelium participates
      actively in TNF-induced neutrophil respiratory burst activity by expressing
      platelet-activating factor (PAF) in response to initial neutrophil H2O2 release.
      Three findings are shown that favor such a mechanism. First, PAF receptor
      antagonists reduced H2O2 release by TNF-activated neutrophils placed on
      endothelium approximately by 50%, whereas H2O2 responses by neutrophils placed on
      serum-coated polystyrene remained intact. Second, preincubation of HUVEC with
      known PAF-inducing agents PMA, H2O2, and thrombin, followed by fixation, enhanced
      neutrophil H2O2 release in response to TNF. H2O2 release by these neutrophils was
      sensitive to the presence of PAF receptor antagonists, whereas H2O2-release from
      neutrophils placed on fixed nonactivated endothelial cells was not. Finally,
      replacing endothelium by monolayers of human renal cortical epithelial cells and
      human fibroblasts, cells that are known to produce less PAF than endothelial
      cells, reduced the effect of PAF receptor antagonists. P-selectin expression and
      IL-8 release, two other ways by which endothelial cells might influence H2O2
      release by TNF preincubated neutrophils, were examined in parallel, and were
      found not to influence TNF-induced neutrophil H2O2-release. We conclude that
      during neutrophil-endothelial interaction in inflammation, endothelium modulates
      the toxic response of neutrophils to TNF. Endothelial cell-associated PAF, but
      not endothelial cell IL-8 release and P-selectin expression, is likely to
      participate in TNF-induced neutrophil respiratory burst activity.

PMID- 7529803
TI  - A Th0/Th2-like function of CD4+CD7- T helper cells from normal donors and HIV
      infected patients.
AB  - We previously reported the expansion during HIV infection of a subset of CD4+ T
      cells characterized by a lack of CD7 cell surface expression. This CD4+CD7-
      subset showed in normal donors a lower cell proliferation than CD4+CD7+
      autologous cells after CD3 triggering or CD28 costimulation. Our aim was to
      further characterize the Th function of this CD4+CD7- T cell subset, both in
      normal donors and in HIV-infected patients. Their CD4+CD7- cell proliferation and
      cytokine secretion were analyzed after cell-sorting and co-stimulation of the CD3
      and CD28 pathways. In normal donors, the IL-2 produced by CD4+CD7- cells in
      response to a CD3 plus CD28 costimulus represented 50 +/- 28% of the autologous
      CD4+CD7+ cell IL-2 secretion. In addition, the CD4+CD7+ T cells produced higher
      amounts of IL-4 and IL-10 than the CD4+CD7+ cells with mean CD4+CD7-: CD4+CD7+
      ratios of 5.4 +/- 4.5 and 26 +/- 25, for IL-4 and IL-10, respectively, whereas
      the IFN-gamma production was similar in both subsets. After a triggering of the
      CD3 complex alone, significant amounts of IL-2 were detectable in CD4+CD7+ cell
      supernatants only; conversely, IL-4 and IL-10 could be detected only in the
      culture medium from CD4+CD7- T cells. This profile of cytokine production was
      maintained both over time and at the clonal cell level in the CD4+CD7- T cell
      subset. In HIV-infected patients, the CD4+CD7- T cell expansion observed in
      relationship with disease progression was associated to an in vivo activation of
      the CD4+CD7- cells, as assessed by cell surface expression of the HLA-DR, CD25,
      CD71, and CD57 markers. The CD4+CD7- T cells from HIV-seropositive patients
      showed the same imbalance of cell proliferation and IL-2, IL-4, and IL-10
      production as observed in normal donors despite low levels of proliferation and
      cytokine production. Together, our data indicate that the lack of CD7 expression
      defines a CD4+ Th cell subset with a Th0/Th2-like profile of cytokine secretion
      in normal individuals. The CD4+CD7- subset is expanded during HIV infection and
      characterized by the same although impaired profile of cytokine production. These
      CD4+CD7- T cells might play a role in the Th cell dysfunctions observed in HIV
      infection.

PMID- 7529804
TI  - Interaction between CD40 and its ligand gp39 in the development of murine lupus
      nephritis.
AB  - We investigated the role of gp39-CD40 interaction in the development of
      glomerulonephritis in lupus mice. In contrast to normal mice, lupus mice had much
      higher percentages of intensely gp39+ T cells in their spleens even at the
      preautoimmune age of 1 mo, and the further increase in gp39 expression by anti
      CD3 Ab stimulation was markedly greater in lupus T cells. The pathogenic
      autoantibody-inducing ability of Th clones and splenic Th cells from lupus mice
      could be blocked in vitro by anti-gp39 Ab. Acceleration of lupus nephritis by the
      transfer of pathogenic autoantibody-inducing Th clones in vivo could also be
      completely blocked by anti-gp39 Ab. Surprisingly, a brief treatment of lupus mice
      with anti-gp39 Ab had a sustained beneficial effect on their spontaneous disease
      long after the Ab had been cleared from their systems. Only three injections of
      anti-gp39 Ab given to prenephritic lupus mice at 3 mo of age markedly delayed and
      reduced the incidence of lupus nephritis up to 12 mo of age by which time almost
      all the control mice had developed severe glomerulonephritis. Remarkably,
      pathogenic Th cells were left intact in these anti-gp39-treated mice but their B
      cells could not produce pathogenic autoantibodies even 9 mo after the therapy.
      Our studies suggest that blocking the interaction between gp39 on pathogenic Th
      cells and CD40 on lupus B cells at a crucial window of time delays the expansion
      autoimmune memory B cells resulting in long-term therapeutic benefits.

PMID- 7529805
TI  - Role of B7:CD28/CTLA-4 in the induction of chronic relapsing experimental
      allergic encephalomyelitis.
AB  - T cell activation requires both Ag/MHC recognition and costimulatory signals. The
      present studies were designed to test whether the loss of tolerance to myelin
      basic protein (MBP) requires costimulation by members of the B7 receptor family.
      CTLA-4Ig, a fusion protein ligand for B7-1 and B7-2, was used to assess the role
      of B7-mediated costimulation in chronic relapsing experimental allergic
      encephalomyelitis (EAE) induced by the transfer of MBP specific T cell lines. In
      adoptively transferred EAE, administering CTLA-4Ig to donor mice or during in
      vitro activation of MBP specific-T cells resulted in diminution of clinical
      disease. The presence of CTLA-4Ig during both the immunization and in vitro
      activation stages was most effective in preventing clinical signs of disease.
      This diminution in clinical disease was paralleled by a decreased proliferative
      response and reduced production of IL-2 and IL-4, but not IFN-gamma, after
      antigenic stimulation of encephalitogenic T cells in vitro. In contrast, CTLA-4Ig
      treatment of recipient animals after the transfer of MBP-activated T cells
      affected neither disease course nor severity. These results indicate that
      additional costimulatory pathways may be involved in established EAE, or that
      some cells are independent of costimulation or, alternatively, that CTLA-4Ig does
      not enter brain parenchyma in therapeutic concentrations. Thus, we conclude that
      costimulation provided by B7 molecules plays a major role in the development of
      encephalitogenic T cells and in the establishment of chronic relapsing EAE, a
      prototypic CD4+ T cell-mediated autoimmune disease.

PMID- 7529806
TI  - Immunoregulatory CD8+ cells recognize antigen-activated CD4+ cells in myasthenia
      gravis patients and in healthy controls.
AB  - CD8+ cells inhibiting the response of CD4+ cells exist in rodents, recognizing
      epitopes unique to a CD4+ clone (Ids) or expressed by all activated CD4+ cell
      (ergotypes). Stimulation of CD8+ cells recognizing ergotypes shared by all Ag
      activated CD4+ cells would be useful for treatment of diseases involving
      undesirable CD4+ responses to ill defined Ags, such as many autoimmune diseases
      and allergies. As a first step toward demonstrating the existence of anti
      ergotype CD8+ immunoregulatory cells in humans, we investigated here whether CD8+
      cells recognizing Ag-activated CD4+ cells exist in autoimmune and healthy humans.
      CD4+ cells specific for human muscle acetylcholine receptor, tetanus, or
      diphtheria toxoids were propagated from patients with myasthenia gravis patients
      and healthy controls. Ag-activated CD4+ cells were irradiated and used as Ag to
      test the response of CD(4+)-depleted CD(8+)-enriched PBMC (CD8+ PBMC) from
      myasthenic patients and controls and to propagate short-term CD8+ cell lines from
      CD8+ PBMC. In both patients and controls CD8+ PBMC and CD8+ lines responded
      vigorously to autologous Ag-activated CD4+ cells. The CD8+ lines responded
      equally well to the Ag-activated CD4+ cells of different Ag specificity,
      suggesting that they recognized CD4+ ergotypes. They did not seem to respond to
      CD4+ cells activated by PHA. The CD8+ cells recognized class I-restricted
      epitopes, as their response to activated CD4+ cells was suppressed by anti-class
      I Ab. CD8+ cells recognizing Ag-activated CD4+ were present cells in the controls
      for 5 to 12 wk after immunization. In myasthenic patients, CD8+ cells recognizing
      activated anti-acetylcholine receptor CD4+ cells seemed to be always present.

PMID- 7529810
TI  - Nomenclature of the human interferon genes.

PMID- 7529811
TI  - Nomenclature of the human interferon proteins.

PMID- 7529812
TI  - The Palliative Care Consultation Service of the Medical College of Wisconsin.
AB  - Palliative care has not become a routine aspect of US academic medicine due to
      lack of reimbursement for clinical services, little research funding, and the
      perception that care for the terminally ill is not important in academic medical
      centers. This article describes the clinical activities of a new Palliative Care
      Consultation Service (PCS) for inpatients and outpatients, which was started at
      the Medical College of Wisconsin in April 1993. The goals of the PCS are to
      provide symptom control, assist with end-of-life decision making, and serve as a
      resource for appropriate discharge planning for all dying patients, not only
      those with cancer. Since its inception, an average of five consultations per week
      have been seen. Pain and end-of-life decisions were the most frequent reasons for
      consultation. Thirteen different clinical services consulted the PCS, most
      commonly internal medicine and oncology. Cancer and acquired immunodeficiency
      syndrome (AIDS) were the most frequent diagnoses. The PCS has also been used as a
      resource for assessment of inpatients with chronic nonmalignant pain who were
      believed to be drug addicts. The PCS has received widespread acceptance by the
      medical, nursing, and support staffs. The clinical and educational role of a
      dedicated palliative care service in academic medicine is discussed.

PMID- 7529807
TI  - V gamma 2V delta 2 TCR-dependent recognition of non-peptide antigens and Daudi
      cells analyzed by TCR gene transfer.
AB  - The predominant subpopulation of gamma delta T cells in human peripheral blood
      expresses TCR V region genes V gamma 2 paired with V delta 2. Previous studies
      have shown that these V gamma 2V delta 2+ T cells proliferate in response to
      Daudi Burkitt lymphoma cells, synthetic alkyl phosphate molecules including
      monoethylphosphate (MEP), and an Ag chemically similar to MEP purified from
      mycobacterial extracts of several species including Mycobacterium tuberculosis.
      This proliferation is polyclonal and determined by the TCR V gene. However,
      because these alkyl phosphate molecules are so distinct from conventional
      peptides and superantigens, we questioned whether these substances induce gamma
      delta T cell proliferation via TCR-dependent recognition. Here we report that
      transfection of TCR- Jurkat T cells with cDNA constructs encoding a V gamma 2V
      delta 2 TCR enabled the transfectants to produce IL-2 in response to Daudi cells,
      mycobacterial extract, and MEP. The responses were dose dependent and Ag
      specific. These results demonstrate an essential role for the gamma delta TCR in
      V gamma 2V delta 2 T cell-mediated recognition of non-peptide Ags by human T
      cells and suggest a structural similarity or cross-reactivity between cellular
      and microbial Ags recognized by these gamma delta T cells.

PMID- 7529808
TI  - An enzyme-linked immunosorbent assay for complement regulatory proteins and
      membrane-bound immunoglobulins on intact red blood cells.
AB  - We have developed an ELISA technique to examine RBC-bound molecules in autoimmune
      disorders. In particular, the technique has enabled us to investigate the role of
      some complement regulatory proteins in immune complex transport and to suggest
      that decay accelerating factor (DAF) may be involved in this process. In both
      autoimmune haemolytic anaemia (AHA) and systemic lupus erythematosus (SLE) a sub
      set of individuals was identified, on the basis of patterns of complement
      receptor 1 (CR1) expression on RBC. In these patients, CR1 identified using the
      monoclonal antibody E11 was low or absent whereas CR1 identified using a DAKO
      monoclonal antibody (C3RTo5) was present at normal levels.

PMID- 7529809
TI  - A versatile system for the production of recombinant chimeric peptides.
AB  - Production of chimeric and multimeric peptides is of interest for the analysis of
      topographic relationships between T and B cell stimulatory epitopes. Recombinant
      DNA technology has certain advantages over conventional chemical peptide
      synthesis for the production of peptide constructs of large size (more than 40
      amino acid residues). We describe a methodology which is versatile and
      independent of the expression vector used because it only relies on the
      incorporation of appropriate restriction enzyme sites in oligonucleotides. The
      method was verified using two 20mer sequences from the 38 kDa antigen of M.
      tuberculosis. Peptide 201-220, containing an antibody binding linear epitope, has
      been made immunogenic in vivo when combined with T cell stimulatory peptide 350
      369 in a chimeric peptide. The results demonstrate that a distinct orientation of
      the constituent peptides was essential for achieving optimal immunogenicity.

PMID- 7529813
TI  - Dobutamine as palliative drug in home-care advanced cancer patients.
AB  - We describe a patient with advanced cancer whose severe symptoms of congestive
      heart failure were successfully treated with dobutamine. The intermittent
      intravenous administration of dobutamine 5 micrograms/kg/min for 3 hr per day at
      home enabled control of dyspnea, leg edema, and pain, and increased urine output
      after 1 day. An improvement in renal function was observed in the following days.
      The mechanism and the utility of a palliative approach with dobutamine are
      discussed.

PMID- 7529815
TI  - Adhesive glycoproteins in the pathogenesis of Pneumocystis carinii pneumonia:
      host defense or microbial offense?

PMID- 7529816
TI  - Interaction of vitronectin with Pneumocystis carinii: evidence for binding via
      the heparin binding domain.
AB  - Pneumocystis carinii pneumonia is a major opportunistic infection in patients
      with the acquired immune deficiency syndrome. P. carinii attachment to alveolar
      epithelial cells is considered necessary for growth and replication of the
      organism. Recent studies have focused on the role of adhesive proteins such as
      fibronectin and vitronectin in attachment mechanisms of P. carinii in the
      alveolar space. Whereas the role of fibronectin has been partially characterized,
      less is known about the mechanism of vitronectin interaction with P. carinii. To
      better understand the mechanism underlying this interaction, vitronectin-P.
      carinii binding was characterized with respect to monovalent and divalent cations
      and pH by using an iodine 125-labeled vitronectin binding assay to P. carinii. As
      an example, vitronectin-P. carinii binding was abolished in the presence of 1.0
      mol/L NaCl and enhanced by Ca2+ and Mn2+. Further, periodate and heparin
      treatment of P. carinii significantly reduced vitronectin binding to the organism
      to 10% +/- 1.5% (p < 0.01) and 52% +/- 1.8% (p < 0.05) of control values,
      respectively. There was no competitive inhibition of vitronectin binding to P.
      carinii by using the peptide sequence arg-gly-asp-ser of the cell binding domain.
      The findings suggest that vitronectin, unlike fibronectin, binds to P. carinii by
      a predominantly electrostatic mechanism that likely involves the heparin binding
      domain of vitronectin.

PMID- 7529817
TI  - Effect of aspirin and iloprost on adhesion of platelets to intact endothelium in
      vivo.
AB  - Aspirin has been used for the prevention of platelet thrombi, both
      prophylactically and therapeutically, in a wide variety of conditions. Although
      the dosage used has also varied, it is now suggested that lower doses are as
      efficacious and probably safer than higher doses. Part of the problem in
      determining the amount to be used is that aspirin not only inhibits the formation
      of the proaggregatory thromboxane A2 in the platelet, at any dose, but also that
      it interferes with the production of prostacyclin (antiaggregatory) by the
      endothelial cells in a dose-dependent manner. Previously, utilizing a hamster
      cheek pouch preparation, we demonstrated that platelets would adhere to intact
      endothelium, in vivo, after an otherwise ineffectual dose of thrombin if the
      glycosaminoglycans of endothelial cells that produce antithrombin activity were
      first neutralized by protamine. Reported here is the effect of aspirin on the
      platelet thrombi produced by thrombin in this manner. Aspirin was found to
      inhibit platelet thrombosis by thrombin in low doses (optimum dose 2.5 mg/kg body
      weight), but at higher doses the aspirin was less effective. Actually, the higher
      doses of aspirin promoted platelet thrombus formation by thrombin even in the
      absence of protamine. Infusion of iloprost, an analog of prostacyclin, also
      prevented platelet thrombus formation by protamine and thrombin with or without
      the administration of aspirin, and this infusion overcame the thrombogenicity of
      the higher doses of aspirin. The results of these experiments in the hamster
      suggest that the optimum dosage of aspirin in the clinical treatment of
      prophylaxis of thrombosis in human patients would be 160 mg.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7529818
TI  - The molecular basis of chloride transport in shark rectal gland.
AB  - Transepithelial Cl- secretion in vertebrates is accomplished by a secondary
      active transport process brought about by the coordinated activity of apical and
      basolateral transport proteins. The principal basolateral components are the
      Na+/K(+)-ATPase pump, the Na+/K+/2Cl- cotransporter (symporter) and a K+ channel.
      The rate-limiting apical component is a cyclic-AMP-stimulated Cl- channel. As
      postulated nearly two decades ago, the net Cl- movement from the blood to the
      lumen involves entry into the epithelial cells with Na+ and K+, followed by
      active Na+ extrusion via the pump and passive K+ exit via a channel.
      Intracellular [Cl-] is raised above electrochemical equilibrium and exits into
      the lumen when the apical Cl- channel opens. Cl- secretion is accompanied by a
      passive paracellular flow of Na+. The tubules of the rectal glands of
      elasmobranchs are highly specialized for secreting concentrated NaCl by this
      mechanism and hence have served as an excellent experimental model in which to
      characterize the individual steps by electrophysiological and ion flux
      measurements. The recent molecular cloning and heterologous expression of the
      apical Cl- channel and basolateral cotransporter have enabled more detailed
      analyses of the mechanisms and their regulation. Not surprisingly, since hormones
      acting through kinases control secretion, both the Cl- channel, which is the
      shark counterpart of the CFTR (Cystic Fibrosis Transmembrane Conductance
      Regulator), and the cotransporter are regulated by phosphorylation and
      dephosphorylation. The primary stimulation of secretion by hormones employing
      cyclic AMP as second messenger activates CFTR via the direct action of protein
      kinase A (PKA), which phosphorylates multiple sites on the R domain. In contrast,
      phosphorylation of the cotransporter by as yet unidentified kinases is apparently
      secondary to the decrease in intracellular chloride concentration caused by anion
      exit through CFTR.

PMID- 7529814
TI  - Experimental osteonecrosis of the lunate. Revascularization may cause collapse.
AB  - Is lunate collapse in Kienbock's disease a consequence of spontaneous
      revascularization, leading to focal osteolysis? A literature review of
      osteonecrosis in other locations such as the femoral head and bone allografts
      showed clearly that the loss of mechanical integrity is due to cellular processes
      which follow the spontaneous restoration of blood supply. We found no evidence in
      the literature that the lunate has been shown to be avascular at the time of
      collapse. On the contrary, increased osteoclastic activity has been reported. We
      excised and reimplanted the lunate in two monkeys, and found spontaneous
      revascularization, leading to increased osteoblastic activity. Other parts of the
      bone were destroyed by osteoclasts, leading to collapse. This histological
      example suggests that it may be possible to make an analogy with osteonecrosis in
      other locations. Thus, changes on plain radiography may indicate that the bone is
      revascularized spontaneously. Before performing operative revascularization of
      the lunate, one should consider that revascularization is a probable cause for
      collapse.

PMID- 7529819
TI  - Hyperfibrinolysis during intracranial surgery: effect of high dose aprotinin.
AB  - A patient undergoing intracranial surgery developed disseminated intravascular
      coagulation with life threatening peroperative bleeding. Thromboelastography
      established the diagnosis of hyperfibrinolysis, usually a fatal complication of a
      neurosurgical operation. With the administration of a high dose regimen of
      aprotinin (Trasylol) the haemorrhage was controlled and the hyperfibrinolytic
      state reversed. Evaluation of blood samples from the jugular bulb suggested that
      there was a pronounced local release of tissue plasminogen activator into the
      circulation.

PMID- 7529821
TI  - Intracellular pH changes produced by glutamate uptake in rat hippocampal slices.
AB  - 1. The mean intracellular pH in area CA1 of rat hippocampal slices was monitored
      fluorescently after loading the cells with the dye BCECF-AM. 2. Including L
      glutamate in the solution superfusing the slice led to the intracellular pH
      becoming more acid. This acidification had a roughly Michaelis-Menten dependence
      on the superfused glutamate concentration with a half-maximal dose around 200
      microM: this value must overestimate the glutamate concentration at most of the
      cells, which will be reduced by uptake. 3. The glutamate-evoked acidification was
      not significantly reduced by blockers of glutamate-gated ion channels [6-cyano-7
      nitroquinoxaline-2,3- dione (CNQX) and D-aminophosphonovalerate (APV)] nor by
      blockers of gamma-aminobutyric acid (GABA)- and glycine-gated channels
      (picrotoxin and strychnine), and so was not produced by H+ entry through alpha
      amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) or N-methyl-D
      aspartate (NMDA) receptor channels nor by HCO3- exit through the chloride
      channels controlled by GABA or glycine. 4. The glutamate-evoked acidification was
      not reduced by tetrodotoxin (TTX), ruling out the possibility of it being
      generated by action potentials. It was also unaffected by saturation of
      presynaptic L-amino-4-phosphonobutanoate (AP4) receptors with AP4. 5. In the
      presence of blockers of glutamate-, GABA-, and glycine-gated channels, the
      acidification showed the pharmacology of glutamate uptake and was reduced by a
      glutamate uptake blocker. 6. The glutamate-evoked acidification showed an ion
      dependence similar to that of glutamate uptake. It was abolished by removal of
      extracellular sodium and was reduced by raising the extracellular potassium
      concentration. It was unaffected by blockers of Na+/H+ exchange (amiloride) and
      Na+/HCO3- cotransport [4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)]
      and so was not produced by the Na+ influx accompanying glutamate uptake changing
      the activity of these carriers. 7. These data show that the glutamate uptake
      carrier acidifies hippocampal cells, possibly because it transports a pH-changing
      anion out of the cell as in salamander glial cells. Glutamate uptake may thus
      contribute to activity-induced pH changes in the nervous system.

PMID- 7529820
TI  - Glycine response in acutely dissociated ventromedial hypothalamic neuron of the
      rat: new approach with gramicidin perforated patch-clamp technique.
AB  - 1. We investigated the glycine-induced response in ventromedial hypothalamic
      (VMH) neurons freshly dissociated from 8- to 12-day-old rats using the nystatin
      and gramicidin perforated patch recording modes. The nystatin-formed pores in the
      plasma membrane are permeable for both monovalent cations and anions, whereas
      those formed by gramicidin are permeable only to monovalent cations. Therefore,
      when the patch-pipette contains 150 mM Cl- and gramicidin, the physiological
      intracellular Cl- concentration ([Cl-]i) is undisturbed in the cell-attached
      condition of the pipette. 2. At holding potentials of -40 to -60 mV, glycine
      induced inward currents and outward currents in the nystatin and gramicidin
      perforated patch recording modes, respectively. The values of the half-maximum
      effective concentration (EC50) and the Hill coefficient in the concentration
      response relationships of the glycine responses were 2.9 x 10(-5) M, 1.1, and 4.2
      x 10(-5) M, 1.4, respectively. These values were quite similar in both recording
      modes. 3. The reversal potentials of the glycine responses (EGly) were -1.5 mV in
      the nystatin perforated patch recording and -75.0 to -24.8 mV in the gramicidin
      perforated patch recording. 4. Strychnine (3 x 10(-8) M) inhibited the glycine
      induced outward currents in a competitive manner and the half-inhibition
      concentration (IC50) of strychnine on the 10(-4) M glycine-induced response was
      1.9 x 10(-8) M. 5. The physiological [Cl-]i in the VMH neurons calculated from
      the EGly obtained by the gramicidin perforated patch mode ranged from 6.0 to 43.8
      mM (n = 28).

PMID- 7529822
TI  - Characterization of a muscarinic current that regulates excitability of an
      identified insect motoneuron.
AB  - 1. Application of the muscarinic agonist oxotremorine-M (oxo-M) to isolated
      abdominal ganglia of larval Manduca sexta excited an identified proleg retractor
      motoneuron called PPR. This excitation consisted of a persistent depolarization
      and an increased tendency to generate action potentials. Previous work has
      established that the action of oxo-M is probably mediated by muscarinic
      acetylcholine receptors (mAChRs) on PPR and that oxo-M mimics an afferent-induced
      long-lasting depolarization called the slow excitatory postsynaptic potential
      (sEPSP). 2. Action potentials in the ganglion could be blocked by applying
      tetrodotoxin (TTX) in the bath saline. Under these conditions all excitatory
      postsynaptic potentials in PPR were also blocked, but the depolarizing action of
      oxo-M was unaffected. In the absence of background activity PPR could be voltage
      clamped using a single-electrode switching clamp to study the currents underlying
      the response to oxo-M. 3. At a membrane potential of -50 mV, application of oxo-M
      to the ganglion in the bath saline (3-6 x 10(-7) M) or by brief (20-40 ms) pulses
      from a micropipette into the neuropil (1 x 10(-5) M) evoked an apparently inward
      current called Iox. The mean peak current change in response to pulses was -0.80
      +/- 0.04 nA (n = 48 preparations). 4. The voltage dependence of Iox was
      determined by subtracting the current-voltage relationship for PPR in control
      saline from that during a response to oxo-M. Iox was maximal near the resting
      potential of PPR (-45 to -40 mV), decreasing slightly with hyperpolarization and
      strongly with depolarization. 5. Peak Iox was directly dependent on the bath Na+
      concentration. Complete replacement of Na+ with N-methyl-D-glucamine in the
      saline blocked Iox. Changes in the bath K+ concentration (extracellular K+
      concentration, [K+]o) had only a small effect on Iox. Reducing [Cl-]o from 140 to
      74.5 mM had no significant effect on Iox during a 15-min exposure. Intracellular
      injections of Cl- from a KCl-containing electrode also had no measurable effect
      on Iox. 6. Changes in the bath Ca2+ concentration above or below 2 mM inhibited
      Iox. Furthermore, the divalent cations Ni2+, Co2+, Mg2+, and Ba2+ at millimolar
      concentrations and the Ca2+ channel blocking agents nifedipine and Cd2+ at
      micromolar concentrations inhibited Iox. 7. These results suggest that mAChRs on
      PPR activate an inward current that is persistent, TTX insensitive, voltage
      dependent and carried predominantly by Na+. However, the results cannot eliminate
      the possibility that changes in K+ or Cl- conductances might also be
      involved.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7529823
TI  - Compartmental models of type A and type B guinea pig medial vestibular neurons.
AB  - 1. We have developed compartmental models of guinea-pig medial vestibular nuclei
      neurons (MVNns). The structure and the parameters of the model cells were chosen
      to reproduce the responses of type A and type B MVNns as described in
      electrophysiological recordings. 2. Dynamics of membrane potentials were modeled
      in 46 and 61 branched electrical compartments for Type A and Type B MVNns,
      respectively. Each compartment was allowed to contain up to nine active ionic
      conductances: a fast inactivating sodium conductance, gNa, a persistent sodium
      conductance, gNap, a low-voltage activated calcium conductance, gCa(LVA), a high
      voltage activated calcium conductance, gCa(HVA), a fast-voltage activated
      potassium conductance, gK(fast), a slowly relaxing voltage activated potassium
      conductance, gK(slow), a fast transient potassium channel, gK(A), a slowly
      relaxing mixed sodium-potassium conductance activating at hyperpolarized membrane
      potentials, gH, and a calcium-activated potassium conductance gK(AHP). The
      kinetics of these conductances were derived from voltage-clamp studies in a
      variety of preparations. Kinetic parameters as well as distribution and density
      of ion channels were adjusted to yield the reported electrophysiological behavior
      of medial vestibular neurons. 3. Dynamics of intracellular free [Ca2]i were
      modeled by inclusion of a Ca(2+)-pump and a Na(+)-Ca2+ exchanger for extrusion of
      calcium. Diffusion of calcium between submembraneous sites and the center of an
      electrical compartment was modeled by 25 and 6 shell-like chemical compartments
      for the cell body and the proximal dendrites, respectively. These compartments
      also contained binding sites for calcium. 4. The dynamics of active conductances
      were the same in both models except for gK(fast). This was necessary to achieve
      the different shape of spikes and of spike afterhyperpolarization in type A and
      type B MVNns. An intermediate depolarizing component of the spike
      afterhyperpolarization of type B neurons in part depended on their dendritic
      cable structure. 5. Variation of the low threshold calcium conductance, gCa(LVA),
      shows that the ability to generate low-threshold spike bursts critically depends
      on the density of this conductance. Sodium plateaus were generated when
      increasing the density of gNap. 6. The type B model cell generated rhythmic
      bursts of spiking activity under simulation of two distinct experimental
      conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 7529824
TI  - Extracellular alkaline transients mediated by glutamate receptors in the rat
      hippocampal slice are not due to a proton conductance.
AB  - 1. The ionic mechanism of extracellular alkaline transients mediated by alpha
      amino-3-hydroxy-5-methylisoxazolate-4-propionic acid (AMPA) receptor channels was
      studied in the rat hippocampal slice (area CA1) by means of H(+)-, Ca(2+)- and
      Na(+)-selective microelectrodes. 2. Alkaline transients mediated by selective
      synaptic activation of AMPA receptors were coupled to a transient fall in
      extracellular Ca2+ ([Ca2+]o). 3. Removal of [Ca2+]o blocked the alkaline
      transient evoked by microinjection of AMPA, but had little effect on the
      simultaneous tetrodotoxin-resistant fall in extracellular Na+ ([Na+]o). 4.
      Alkaline transients evoked by microinjection of gamma-aminobutyric acid (GABA)
      were not affected by removal of [Ca2+]o. GABA had no effect on [Na+]o. 5. The
      present results indicate that activity-induced glutamatergic alkaline transients
      in the hippocampal slice are due to an influx of Ca2+, and not to a conductive
      movement of H+ ions across glutamate-gated cation channels.

PMID- 7529826
TI  - Antagonist and partial agonist actions of d-tubocurarine at mammalian muscle
      acetylcholine receptors.
AB  - Currents were elicited by acetylcholine (ACh), by d-tubocurarine (dTC), and by
      mixtures of ACh and dTC, from stably transformed fibroblasts that express fetal
      or adult muscle nicotinic receptors. dTC acted as an antagonist of ACh for
      activation of adult-type receptors, whereas it acted as a weak partial agonist at
      fetal-type receptors. The channel-blocking action of dTC was not apparent at the
      concentrations used. The partial agonism could explain previous observations that
      dTC is less effective at blocking the responses of fetal-type receptors than
      adult-type receptors. Binding of dTC to receptors was independently assayed by
      measuring the reduction of the initial rate of binding of iodinated alpha
      bungarotoxin. Binding of dTC to the two types of receptor was indistinguishable.
      The dose-effect relationship for the interaction of dTC and ACh at fetal
      receptors is consistent with the affinities of dTC measured in binding
      experiments.

PMID- 7529825
TI  - The serotonergic inhibitory postsynaptic potential in prepositus hypoglossi is
      mediated by two potassium currents.
AB  - Synaptic inhibition mediated by the activation of potassium channels has been
      reported from several types of neurons. In each case, despite mediation by
      different neurotransmitters, the K+ conductance underlying the synaptic potential
      is activated by a G protein and inwardly rectifies. We report here a second K+
      current that contributes to synaptic inhibition. Intracellular recordings were
      made from guinea pig nucleus prepositus hypoglossi in vitro, where we have
      described a 5-HT-mediated IPSP. Voltage-clamp analysis of the current induced by
      applied 5-HT revealed two separate conductances: an inwardly rectifying, rapidly
      activating K+ current (IIR) and an outwardly rectifying, slowly activating K+
      current (IOR). IIR was blocked by extracellular Ba2+ (200 microM) and TEA+ (126
      mM). IOR was insensitive to this concentration of Ba2+ and TEA+, but was
      inhibited by Cd2+ and intracellular BAPTA, indicating Ca dependence. Single focal
      electrical stimuli evoked a 5-HT-mediated IPSP, or under voltage clamp, an
      inhibitory postsynaptic current (IPSC). Ba2+ blocked only a component of this
      IPSC, which corresponded to the current caused by IIR. When multiple stimuli were
      applied (to prolong the release of transmitter), the time-dependent current IOR
      was more fully activated, resulting in an augmentation of the IPSC. We conclude
      that the IPSC is caused by both currents and that its amplitude can be modulated
      by the degree to which IOR is activated. This represents a mechanism by which
      synaptic responses can be potentiated.

PMID- 7529827
TI  - Requirement of the hyaluronan receptor RHAMM in neurite extension and motility as
      demonstrated in primary neurons and neuronal cell lines.
AB  - The recently cloned and characterized hyaluronan (HA) receptor RHAMM (receptor
      for HA-mediated motility) has been shown to play a critical role in mechanisms
      underlying the motile capacity of a variety of peripheral cell types.
      Similarities in molecular processes that govern cell locomotion and growth cone
      migration prompted us to investigate whether RHAMM also contributes to neurite
      migration in vitro. In immunohistochemical studies of PC12 cells, NG108-15 cells
      and a neuroblastoma/spinal cord neuronal hybrid cell line (NSC-34 cells) as well
      as rat and human primary neurons, a punctiform RHAMM labeling pattern was
      detected in cell bodies, along processes, and at growth cones. By Western blot
      analysis, the cells lines expressed major RHAMM forms with apparent MW of 60, 75,
      and 116 kDa. Treatment of NG108-15 cells with dibutyryl-cAMP led to a clear
      increase in immunolabeling for RHAMM and enhanced expression of the 60 and 75 kDa
      forms. A polyclonal anti-RHAMM antibody that interferes with HA/RHAMM interaction
      significantly reduced neurite migration of each cell type examined, while another
      directed against a RHAMM repeat sequence thought to promote RHAMM receptor
      aggregation significantly stimulated neurite migration of NSC-34 and rat primary
      neurons. Different monoclonal anti-RHAMM antibodies had differential inhibitory
      actions on neurite movement. Low concentrations (ng/ml) of a peptide
      corresponding to an HA binding domain within RHAMM inhibited neurite migration.
      These results are the first to implicate RHAMM in the mediation of neurite
      motility and migration and to point to the potential importance of HA in this
      process.

PMID- 7529828
TI  - Regulation of voltage-gated ion channels by NGF and ciliary neurotrophic factor
      in SK-N-SH neuroblastoma cells.
AB  - Neurotrophic factors have powerful effects on neuronal differentiation and the
      maintenance of neuronal phenotype, but understanding of their regulation of one
      important aspect of neuronal function, excitability, remains limited. We have
      examined the regulation of voltage-gated ion channels by two unrelated
      neurotrophic factors, NGF and ciliary neurotrophic factor (CNTF), in the SK-N-SH
      neuroblastoma cell line that is responsive to both factors. NGF and CNTF have
      strikingly different neuronal specificities and distributions in the nervous
      system, and might be expected to have significantly different effects on neuronal
      function. Using whole-cell, perforated-patch, and single-channel recording, we
      found that treatment with NGF increased levels of voltage-gated sodium, calcium,
      and potassium currents. In contrast, CNTF treatment increased levels of potassium
      currents only. NGF and CNTF appeared to regulate the same delayed-rectifier
      potassium current; in addition, NGF treatment resulted in increased levels of a
      second potassium current component. Such differential effects of neurotrophic
      factors on the expression of voltage-gated ion channels would have profound
      effects on the excitability of target neurons in vivo.

PMID- 7529829
TI  - Neuronal and glial prostaglandin D synthase isozymes in chick dorsal root
      ganglia: a light and electron microscopic immunocytochemical study.
AB  - Homogenates of chick dorsal root ganglia (DRG) and in vitro cultures of DRG
      neurons are known to synthesize prostaglandin (PG) D2. To specify the PGD
      synthase isozymes controlling PGD2 synthesis in DRG and to identify the DRG cells
      responsible for this synthesis, we applied polyclonal antibodies raised against
      rat brain or rat spleen PGD synthase isozymes to vibratome or cryostat slices of
      DRG previously fixed with a formaldehyde-lysine-periodate mixture and
      permeabilized with Triton X-100. The immunoreactivity indicating rat spleen PGD
      synthase, a glutathione (GSH)-requiring enzyme, was located in satellite cells
      encompassing particular large neurons of class A and in Schwann cells myelinating
      and enwrapping their initial axonal segments. In contrast, the immunoreactivity
      of rat brain PGD synthase, a GSH-independent enzyme, was restricted to particular
      ganglion cell perikarya: 33% of the DRG neurons were immunostained for rat brain
      PGD synthase, including 2% of large class A neurons and 40% of small class B
      neurons. Only 3.3% of rat brain PGD synthase-immunoreactive small B neurons
      coexpressed substance P, indicating that the immunoreactive neurons belong to the
      B1 subclass. By electron microscopy, 71 of 72 immunoreactive DRG cells were
      identified as small B neurons of the B1 subclass, and 71 of 77 B1 neurons were
      immunoreactive for rat brain PGD synthase. These results demonstrate that PGD2
      formation in DRG is regulated by two isozymes: the GSH-requiring isozyme located
      in satellite and Schwann cells and the GSH-independent isozyme-confined to small
      B1 neurons.

PMID- 7529830
TI  - CD9 plays a role in Schwann cell migration in vitro.
AB  - To identify molecules that regulate Schwann cell migration, we have generated a
      panel of monoclonal antibodies against Schwann cell surface antigens that
      modulate Schwann cell migration in in vitro bioassays. One of these antibodies,
      SMRA1, recognizes a 26 kDa Schwann cell surface membrane protein identified here
      as CD9. SMRA1 enhances Schwann cell migration on two biologically relevant
      substrates: living axons of cultured dorsal root ganglion neurons, and cryostat
      sections of sciatic nerve. This CD9-induced regulation of Schwann cell motility
      is correlated with a rise in cytosolic calcium and enhanced tyrosine
      phosphorylation of several Schwann cell proteins. These results, together with
      the findings of Hadjiargyrou and Patterson (1994), implicate CD9 as an important
      regulator of Schwann cell behavior in peripheral nerve.

PMID- 7529831
TI  - Sigma ligands indirectly modulate the NMDA receptor-ion channel complex on intact
      neuronal cells via sigma 1 site.
AB  - To investigate the modulatory effects of sigma ligands on the N-methyl-D
      aspartate (NMDA) receptor-ion channel complex in vivo, we examined the intact
      cell binding of 3H-N-[1-(2-thienyl)cyclohexyl]piperidine (3H-TCP) to cultured
      neuronal cells prepared from fetal rat telencephalon. The 3H-TCP binding was
      saturable, reversible, and inhibited by a selective NMDA receptor antagonist, D
      amino-5-phosphonovaleric acid. MII-limolar Mg2+ inhibited 3H-TCP binding both in
      the absence and presence of L-glutamate. 5-Methyl-10,11-dihydro-5H-dibenzo
      [a,d]cyclohepten-5,10-imine maleate (MK801) inhibited 3H-TCP intact cell binding
      in a competitive manner, while haloperidol inhibited it in a noncompetitive
      manner. The effect of the test drugs to inhibit 3H-TCP intact cell binding was in
      the order of dextromethorphan, haloperidol > (+/-)MK 801 > (+)pentazocine > (
      )pentazocine > DTG > PCP > (+)-N-allylnormetazocine [(+)SKF 10047] > (+)3-(3
      hydroxyphenyl)-N- (1-propyl)piperidine [(+)3-PPP] > (-)SKF 10047 > (-)3-PPP. The
      IC50 values of the six sigma ligands for 3H-TCP binding were closely correlated
      with the Ki values of the corresponding drugs for DTG site 1 in the guinea pig
      brain reported by Rothman et al. (1991). These findings suggest that the sigma
      ligand indirectly modulates the NMDA receptor ion channel complex, presumably
      through sigma 1 sites in vivo as well as in vitro.

PMID- 7529833
TI  - [Nasal decongestion evaluated by acoustic rhinometry].
AB  - Acoustic rhinometry measures the cross-sectional area of the nasal cavity based
      on changes in acoustic impedance. The volume of the nasal cavity can be
      calculated by mathematical integration of the cross-sectional areas. One of the
      advantages of this procedure is that repeated measurements can be quickly
      performed non-invasively. In this study, we analyzed the mechanisms of nasal
      mucosal decongestion after applying vasoactive agents. The experiments were
      performed in normal adult volunteers (17 males, 3 females) who gave their
      informed consent to participate in this study. Three vasoactive agents (0.1%
      epinephrine, 0.5% phenylephrine hydrochloride, 0.5% oxymetazoline hydrochloride),
      two alpha-receptor antagonists (0.2% phenoxybenzamine, 0.4% yohimbine) and a
      local anesthetic (4% lidocaine) were used. In order to apply the agents precisely
      and safely, we attached a 6mm diameter disc moistened with 0.1 ml of solution to
      the anterior portion of the inferior turbinate unilaterally for fifty seconds.
      After removing the disc, acoustic measurements were performed for an hour. To
      analyze data we divided the nasal cavity into three portions, i.e., anterior,
      middle and posterior. Volume changes in each portion are expressed as
      percentages. Immediately after applying phenylephrine and oxymetazoline,
      ipsilateral volume in the anterior portion began to increase, and then extended
      posteriorly. The level of decongestion remained unchanged for an hour.
      Contralateral volume decreased in all portions. When epinephrine was applied,
      mucosal decongestion occurred first followed by congestion in all portions of the
      ipsilateral side after 20 minutes. Mucosal congestion occurred in all portions of
      the contralateral side. After applying phenoxybenzamine or yohimbine for ten
      minutes, we administered vasoactive agents topically. Pretreatment with alpha-1
      antagonist almost totally suppressed the mucosal decongestion caused by
      phenylephrine and oxymetazoline. Contralateral congestion was decreased by
      antagonizing the suppression of ipsilateral decongestion. After application of
      lidocaine for ten minutes, phenylephrine still caused ipsilateral decongestion
      only in the anterior portion, but decongestion of the middle and posterior
      portion and congestion on the contralateral side totally disappeared. These
      findings suggest the following conclusions: 1) decongestion evoked by adrenergic
      agents is probably caused by direct activation of alpha-1 receptors, 2)
      decongestion of the middle and posterior portions is evoked by drug particles
      conveyed by ciliary movement, and 3) the contralateral response is probably
      related to the activation of sensory nerves on the ipsilateral side.

PMID- 7529832
TI  - Photolysis of caged Ca2+ facilitates and inactivates but does not directly excite
      light-sensitive channels in Drosophila photoreceptors.
AB  - Substantial evidence implicates the phosphoinositide cascade in invertebrate
      phototransduction, but the final pathway of excitation remains obscure. In order
      to test the hypothesis that Ca2+ is the excitatory messenger rapid concentration
      jumps of cytosolic Ca2+ were achieved in dissociated Drosophila photoreceptors by
      flash photolysis of the caged Ca2+ compounds DM-nitrophen and nitr-5. Both
      compounds were introduced via patch pipettes used to record whole-cell currents.
      Calibrations using INDO-1 and Mag-INDO-1 indicated that photolysis of DM
      nitrophen (5 mM loaded with 4 mM Ca2+), raised Ca, to ca. 20-50 microM, and nitr
      5 (same loading) to ca. 1-2 microM. In mutants lacking light responses (ora,
      lacking rhodopsin; norpA, lacking phospholipase C; trp, which is inactivated by
      conditioning lights), the only current evoked by photolysis of DM-nitrophen was a
      small inward current with no detectable latency. This current did not reverse at
      +80 mV and was blocked by substitution of external Na+ for Li+, suggesting it
      represents activation of an electrogenic Na+/Ca2+ exchanger. A similar current
      was also the only current elicited by caged Ca2+ during the 5 msec latent period
      in wild type (WT) photoreceptors. To investigate possible modulatory effects of
      caged Ca2+ on the light-activated conductance, cells were first stimulated with a
      saturating light stimulus, itself incapable of releasing significant Ca2+, and
      then the photolytic flash was discharged during the response. During the rising
      phase of the response, photolysis of DM-nitrophen (but not nitr-5) induced a
      pronounced facilitation in WT photoreceptors. When photolysed during the plateau
      phase both DM-nitrophen and nitr-5 induced a rapid inactivation of the light
      induced current. By contrast, in trp photoreceptors, which lack one class of Ca2+
      permeable light-sensitive channel, photolysis of DM-nitrophen induced a
      significant facilitation during the falling phase of the response, but during the
      rising phase photolysis significantly depressed the overall response. In
      conclusion, caged Ca2+ failed to activate any channels in Drosophila
      photoreceptors but profoundly affected the light-dependent channels once they
      have been activated.

PMID- 7529834
TI  - Wet autoclave pretreatment for antigen retrieval in diagnostic
      immunohistochemistry.
AB  - Interest has recently been shown in adapting the microwave oven heating technique
      for antigen retrieval to routine diagnostic immunocytochemical practice. Although
      it has proved effective as a specialist method for individual antigen
      localization in many laboratories, it has certain drawbacks which have hampered
      its wider routine application. These include the need to monitor the sections
      during the microwave treatment to prevent damage or drying, the limited number of
      sections that can be accommodated in the microwave oven, and the inevitable
      alteration in nuclear morphology induced by the microwaves. In order to obviate
      these difficulties, we have modified the wet autoclave method of Shin et al. (Lab
      Invest 1991; 64: 693-702) as a routine technique for retrieval of a variety of
      cell surface, cytoplasmic, and nuclear antigens in formalin-fixed and paraffin
      embedded tissue. The technique produces even enhancement of several refractory
      antigens in anatomically different sites and has the potential to handle reliably
      up to 200 sections at a time without significant damage to the section or to
      nuclear morphology.

PMID- 7529835
TI  - Biological monitoring of occupational exposure to electrophilic compounds.
AB  - Electrophilic compounds are widely used in industry. Plastic and dyeing
      industries are foremost examples of sites where workers are exposed to
      electrophilic compounds. Besides their immediate effect on different body
      systems, electrophilic compounds include most mutagenic and carcinogenic
      substances. The present study was carried out to elucidate the possibility of
      using nonselective assays in the biological monitoring of occupational exposure
      to electrophilic compounds. The study included a total number of 225 workers
      selected from the Plastic and Battery Company where workers are exposed to
      styrene (n = 70), and the Kafr El Dawar chemical and Dyeing Company where workers
      are exposed to aniline (n = 60) and benzidine (n = 25). Workers exposed to diesel
      engine exhaust were selected from a bus garage in Smoha (n = 70). A comparison
      group consisting of 141 subjects was selected from the administrative departments
      of the selected factories. The biochemical tests carried out on each subject
      included: (1) estimation of the biological indices of exposure: urinary mandelic
      acid and benzidine, blood methemoglobin, and carboxyhemoglobin, (2) liver and
      kidney function tests; and (3) nonselective biochemical parameters of early
      detection of carcinogenic and mutagenic risk: urinary thioether levels, urinary
      RNase and alpha esterase activities. The study revealed that two out of three
      nonselective assays have been affected by occupational exposure to electrophilic
      compounds. These were the urinary thioethers and RNase levels. Their
      determination is recommended in the biological monitoring of workers exposed to
      such agents especially in developing countries.

PMID- 7529836
TI  - Distribution of procollagen type III, collagen type VI and tenascin in oral
      submucous fibrosis (OSF).
AB  - The distribution of procollagen type III, collagen type VI and tenascin was
      studied in biopsy specimens from the buccal mucosa of 19 Indian women with
      confirmed oral submucous fibrosis (OSF) using the immunogold-silver staining
      technique. Immunohistochemistry revealed a loss of stainable procollagen type III
      and collagen type VI in the fibrotic zones of oral submucous fibrosis compared to
      normal oral mucosa. Tenascin was noted only very faintly at the subepithelial
      basement membrane. The present study showed that procollagen type III and
      collagen type VI in OSF were expressed in a specific pattern which allows a clear
      differentiation between fibrotic areas and adjacent apparently normal connective
      tissue stroma. Loss of procollagen type III, and therefore a probable
      predominance of collagen type I in collagen fiber bundles, and an almost complete
      loss of collagen type VI might explain the stiffness of the oral mucosa in
      patients with OSF. The immunohistochemical findings provided evidence that the
      process of fibrosis starts in the deeper subepithelial connective tissue stroma
      and not close to the subepithelial basement membrane. Further studies are
      required to determine whether OSF is due to increased or altered synthesis and
      deposition of extracellular matrix proteins, altered fibrolysis or both.

PMID- 7529838
TI  - Validity of acute phase proteins as markers of disease activity.
AB  - It has long been recognized that various rheumatic diseases, including rheumatoid
      arthritis (RA), are associated with a rise in concentration of acute phase
      proteins, particularly C-reactive protein (CRP) and serum amyloid A. The levels
      of these 2 proteins increase very rapidly over hours after the acute phase
      response is initiated. However, at present, only the measurement of CRP is widely
      available. Studies have shown that CRP is a better indicator of disease activity
      than erythrocyte sedimentation rate. CRP also appears to correlate with, and be
      predictive of, radiographic progression in RA. Although CRP has been shown to
      reflect disease activity and radiographic progression, there appears to be
      discordance between CRP response and drug therapy. With nonsteroidal anti
      inflammatory drugs, there is essentially no change in the CRP response. However,
      CRP levels have been shown to decrease in patients who respond to disease
      modifying antirheumatic drugs. It is possible, therefore, that CRP could be used
      as an early predictor of response to therapy.

PMID- 7529837
TI  - Reduced number of Langerhans cells in oral mucosal washings from HIV-1
      seropositives.
AB  - In order to elucidate mucosal immunity in HIV-1 seropositive individuals, we
      investigated oral mucosa washings from 20 HIV-1 seropositive patients for the
      presence of Langerhans cells (LC) and HIV-1 antigen-positive cells, and compared
      the results with those obtained from 20 HIV-1 seronegative healthy individuals.
      Monoclonal antibodies directed against CD1a, HLA-DR, CD3, and p24 were used to
      identify LC, T cells and HIV-1 core-antigens, respectively. In oral mucosa
      washings from HIV-1 seropositive patients there was a significant reduction in
      the number of CD1a+ cells as compared with the healthy subjects. HIV-1 antigen
      positive cells were not detected. The reduction of LC in oral mucosa washings
      from HIV-1 seropositive patients is probably associated with HIV-1 infection. The
      frequent occurrence of oral mucosal disorders in HIV-1 infected patients may in
      part be caused by a reduced LC-number and/or function.

PMID- 7529839
TI  - Acute-phase reactant proteins and antioxidants in rats intoxicated chronically
      with paraquat.
AB  - Paraquat dichloride at 250 ppm in the diet was fed continuously to rats. Though
      no apparent effect of paraquat was observed until 10 d, some rats then began to
      show several symptoms such as diarrhea, anorexia, epistaxis, and hypokinesia, and
      in some cases rats died after this period. The biochemical examination of plasma
      components revealed appreciable changes in the concentrations of an acute-phase
      reactant protein and some vitamins that act as antioxidants. alpha-Cysteine
      proteinase inhibitor increased by 5-fold, and vitamin C and its radical increased
      by 1.5- and 1.7-fold, respectively, whereas alpha 1 proteinase inhibitor
      decreased slightly. Paraquat enhanced the cysteine proteinase inhibitor levels in
      lung, liver, and kidney by 6.2-, 6.0-, and 4.5-fold of control, respectively.
      Among three components of alpha-cysteine proteinase inhibitor, the T kininogen
      level of treated rat plasma was about eight-fold higher than control, whereas the
      high-molecular-weight kininogen level was unchanged. The large increment of T
      kininogen was also seen in lungs of the treated rats.

PMID- 7529840
TI  - [Type III procollagen N-terminal peptide and type IV collagen-7S level in the
      serum and BALF of patients with non-Hodgkin's lymphoma before and after
      chemotherapy].
AB  - Combination chemotherapy regimens using multiple agents have been reported to
      produce long term survival in patients with non-Hodgkin's lymphoma (NHL).
      However, the adverse effects of those regimens, particularly pulmonary
      complications, have resulted in fatalities. We measured P-III-P and type IV
      collagen-7S level in the serum and BALF of 23 previously untreated NHL patients
      who underwent COP-BLAM III chemotherapy in which a high dose of bleomycin (BLM)
      was used, and studied the relationship between those parameters and the pulmonary
      functions in those patients. The parameters and pulmonary function were measured
      before the first course and after the completion of the fourth course of
      chemotherapy. As for pulmonary function, chemotherapy produced an increment of
      %DLCO value but no change in PaO2, %VC, and %FEV1.0. While serum P-III-P levels
      remained unchanged, P-III-P levels in BALF slightly decreased after the
      chemotherapy. Type IV collagen-7S levels both in serum and BALF showed no change
      after the chemotherapy. Serum P-III-P levels after the chemotherapy were
      significantly correlated with both total cell counts and lymphocyte counts in the
      BALF. But there was no correlation between serum P-III-P levels and %DLCO. Mild
      and early-Stage fibrosis was observed in the lungs of the patients who were
      treated with COP-BLAM III. Pulmonary adverse effects are not likely to be
      associated with the total administered dose of BLM, but are associated with
      individual susceptibility to BLM toxicity. Our results suggest that the
      chemotherapy should be discontinued or the dose of BLM should be reduced if the P
      III-P level in BALF increases.

PMID- 7529843
TI  - [Complete remission induced by combined treatment with all-trans retinoic acid
      (ATRA) and granulocyte colony-stimulating factor (G-CSF) in a patient with
      relapsed acute promyelocytic leukemia].
AB  - In February, 1990, a 49-year-old man was admitted with petechia and gingival
      bleeding. The peripheral blood showed 5,200 leukocytes/microliters including 73%
      abnormal promyelocytes and 24,000/microliters platelets. Bone marrow puncture
      revealed that nucleated cell count was 331,250/microliters including 85.4%
      abnormal promyelocytes with 46XY, i(17q) chromosome. Coagulation tests revealed
      DIC. He was diagnosed as having acute promyelocytic leukemia, and he was treated
      with the BHAC-DMP protocol. He achieved complete remission, and received
      consolidation therapy and maintenance therapy. However, he relapsed in May, 1991
      with 46XY, 16q-, i (17q) chromosome. He was treated with BHAC-MV protocol and
      again achieved complete remission. In June, 1992, he re-relapsed and 3.6% blasts
      and 10% abnormal promyelocytes was found in his bone marrow. He was treated for
      14 days with 15 mg Aclarubicin without any change. Then he was treated with 60 mg
      All-trans retinoic acid (ATRA). After administration of ATRA, his peripheral
      blood leukocyte count increased temporarily but bone marrow suppression
      continued. Then he received continuous subcutaneous infusion of 24 micrograms/day
      granulocyte colony-stimulating factor (rhG-CSF). After treatment with ATRA and
      rhG-CSF, he entered a third complete remission.

PMID- 7529841
TI  - [A phase III trial of subcutaneous administration of rhG-CSF in aplastic anemia].
AB  - To evaluate the efficacy and safety of subcutaneous administration of recombinant
      human granulocyte colony-stimulating factor (rhG-CSF) in aplastic anemia (AA), 21
      patients were given a daily subcutaneous dose of 200 micrograms/m2 of KRN8601 for
      4 weeks. When the blood neutrophil count did not reach 2,000/microliters within 2
      weeks, the dose was increased to 400 micrograms/m2. A marked neutrophilic
      response was obtained in all 9 patients with non-severe AA and in 9 out of the 12
      patients with severe AA, yielding a response rate of 85.7%. Adverse effects
      included lumbago in one patient and elevation of serum enzyme levels in 6
      patients, but did not prohibit further treatment. These results suggest that
      subcutaneous administration of KRN8601 is safe and useful in improving
      neutropenia in AA.

PMID- 7529842
TI  - [A phase III trial of subcutaneous administration of rhG-CSF in the
      myelodysplastic syndromes].
AB  - To evaluate the safety and efficacy of subcutaneous administration of recombinant
      human granulocyte colony-stimulating factor in the myelodysplastic syndromes
      (MDS), 20 patients were given a daily dose of 50 micrograms/m2 of KRN8601 for 4
      weeks. When the blood neutrophil count did not reach 2,000/microliters within 2
      weeks, the dose was increased to 100 micrograms/m2. A marked neutrophilic
      response was obtained in 17 of the 18 evaluable patients (94.4%), irrespective of
      the MDS disease type. Five patients showed a platelet increase, 3 of which also
      showed an erythroid improvement. To maintain neutrophil levels greater than
      1,000/microliters, 12 patients were treated with KRN8601 for 4 weeks. A dose of
      25 to 50 micrograms/m2 3-4 times a week served to this end in 8 patients and 100
      micrograms/m2 three times a week or daily in the remaining 4 patients. One
      patient with RAEB progressed to acute myeloid leukemia 8 weeks after KRN8601. The
      treatment was well-tolerated in the majority of patients with no severe
      toxicities. These results suggest that subcutaneous administration of KRN8601 is
      safe and useful in the treatment of cytopenias in MDS.

PMID- 7529845
TI  - [Blood proteinase inhibitors and cathepsin D in diffuse peritonitis].
AB  - There were 52 patients with a diffuse peritonitis examined. The level of a
      proteinases alpha 1-inhibitor, alpha 2-macroglobulin, trypsin inhibitor,
      cathepsin-D was studied. Results witnesses the high activity of proteinases
      inhibitors cathepsin-D in the early, postoperative period. The level of alpha 2
      macroglobulin and cathepsin-D in an elderly and senile patients approximated to
      normal values up to the 7-9th day after the operation. The dependence of
      proteinases inhibitors and cathepsin-D contents from the severity of peritonitis
      course, the number of interventions done to the patient, and the use of
      autologous blood photomodifization in the complex of treatment were not revealed.

PMID- 7529847
TI  - [Fetal supraventricular extrasystole: indication for fetal echocardiography?].
AB  - The purpose of this study was to assess the incidence of congenital heart disease
      (CHD) in fetuses with premature atrial contractions (PAC) and to check whether
      these fetuses should be referred for a special fetal echocardiogram. Out of 120
      fetuses with PACs and 75 fetuses with CHD both conditions were present in only 9
      fetuses (= 7.5%). Two pregnancies were terminated because of associated severe
      fetal anomalies. After birth PACs disappeared in all other cases spontaneously.
      Despite higher numbers, the incidence of fetal CHD was not statistically
      significant higher in fetuses with PACs. Thus, recognition of fetal PACs should
      lead to a referral for a special fetal echocardiographic examination.

PMID- 7529848
TI  - Univariate tolerance regions for fibrinogen, antithrombin III, protein C, protein
      S, plasminogen and alpha 2-antiplasmin in children using the new Automated
      Coagulation Laboratory (ACL) method.
AB  - To avoid misclassification of lowered or enhanced coagulation proteins in
      childhood the purpose of this study was to establish functional normal ranges for
      healthy children aged 6 months to 16 years. PT, aPTT, fibrinogen, antithrombin
      III, protein C, protein S, plasminogen and alpha 2-antiplasmin were tested using
      the new Automated Coagulation Laboratory (ACL) method. Values for PT, aPTT,
      fibrinogen, antithrombin III, plasminogen and alpha 2-antiplasmin were closely
      comparable in all children although we found a minimum range of 61% in children
      aged 8 to 16 years in plasma concentrations of alpha 2-antiplasmin. Children <
      2.5 years showed reduced lower boundaries encompassing 95% of the population for
      protein C and protein S activity, although medians for protein S activity were
      similar in all children. The rapid and automatic determination of functional
      coagulation proteins using chromogenic substrates on the ACL 300 (25-50
      microliters citrated plasma/test) renders the possibility to realize a screening
      program for inherited thrombotic syndromes in a routine laboratory.

PMID- 7529846
TI  - [Use of transcatheter intra-arterial infusion of drug mixtures in the combined
      treatment of patients with obliterating vascular diseases in the terminal stage
      of limb ischemia].
AB  - Experience of treatment of 215 patients with obliterating diseases of the vessels
      in terminal stage using the method of transcatheter medicinal mixtures infusion
      was summarized. Use of original method permitted to avert the gangrene appearance
      in 65% of patients, to lower the amputation level--in 15%; in 20% of patients the
      result was unsatisfactory, high limb amputation was conducted to them.

PMID- 7529844
TI  - [Evaluation of pulmonary function and bronchoalveolar lavage fluid in elderly non
      Hodgkin's lymphoma before and after COP-BLAM III therapy].
AB  - We investigated pulmonary function and bronchoalveolar lavage fluid (BALF) before
      and after COP-BLAM III therapy in elderly patients with non-Hodgkin's lymphoma
      (NHL). The patients consisted of 8 men and 5 women, over 60 years of age, with
      previously untreated NHL. The PaO2 averaged 86.5 +/- 7.6 mmHg before treatment,
      and 69.3 +/- 9.2 mmHg after treatment. Six Patients showed a decrease in PaO2 to
      less than 20 mmHg. Percent (%) carbon monoxide diffusion capacity was 91.4 +/-
      7.1% before treatment and 69.6 +/- 11.5% after-treatment, and 8 patients showed a
      decrease of at least 20%, whereas there were no definite changes in percent vital
      capacity or the percent of forced expiratory volume in one second. After BALF
      collection, the total cell count was slightly increased and the lymphocyte count
      was also increased after treatment, whereas there were no significant changes in
      neutrophil or eosinophil counts. There were no significant changes in T-cell or B
      cell counts after treatment. The CD4/CD8 was 0.51 before treatment and 1.65 after
      treatment in patients without pulmonary complications, showing a tendency to
      increase, while the low ratio before treatment, 0.24, was nearly unchanged after
      treatment in those who developed pneumonia during their course. Considerable
      attention should be paid to pulmonary complications. As a result of chemotherapy,
      lymphocytic infiltration was observed subclinically in the lung, suggesting that
      changes in the local pulmonary immune system may be involved in the occurrence of
      pulmonary complications.

PMID- 7529849
TI  - Study of drug distribution in hair by infrared microscopy visualization.
AB  - Infrared microscopy has been shown to be a unique method of analysis for drugs-of
      abuse determinations in hair, with the ability to analyze only the central core,
      or medulla region, of sectioned hair. By spectrally mapping infrared functional
      groups related to the various drugs, a three-dimensional image of the drug
      location can be obtained from cross-sectional and laterally microtomed hairs.
      This technique eliminates the question of externally contaminated hair by
      analyzing only that portion of the hair that is formed from within the root where
      ingested material would be transported. Results from these tests have shown a
      direct correlation between drug and medulla presence in the hair. There are
      occasional occurrences of drug in nonmedullated hair, but the drug distribution
      across the hair is entirely different in these cases. Spiked or doped hair has
      been shown to be the exact opposite of drug-ingested hair; the drugs spike into
      the hair better in nonmedullated portions. From these mapped images, two routes
      of drug incorporation into the hair can be postulated. The more prominent would
      be through the root, where the hair shaft is formed, with the drug binding to the
      medulla material. A second less prevalent route would be from the exterior
      through the cuticle via perspiration, as in spiking. The spectral data have also
      shown that different drugs bind differently to the various hair materials.

PMID- 7529850
TI  - Flow cytometric measurement of proliferation-associated nuclear antigen P105 and
      DNA content in immuno-proliferative small intestinal disease (IPSID).
AB  - Immunoproliferative small intestinal disease (IPSID), most common in
      Mediterranean countries, is characterized by lymphomatous infiltration of the
      small intestine and is usually associated with the synthesis of anomalous
      immunoglobulin alpha heavy chains. Flow cytometric analysis of DNA content, S
      phase fraction, and quantitative analysis of the proliferation-associated nuclear
      antigen, P105, were performed in 23 patients with IPSID to determine if they
      could be used as prognostic indicators in this disease. Eighteen patients had low
      grade, two had intermediate-grade, and three had high-grade lymphoma. Eight
      patients had clinical stage IE disease, 12 had stage IIE, and three had stage
      IIIE disease. Eleven patients survived > 5 yr (good prognosis), four survived
      between 2-5 yr (intermediate prognosis), and eight survived 2 yr or less (poor
      prognosis). The S phase fraction of patients with poor prognosis was
      significantly higher than those with intermediate or good prognosis (P < 0.004).
      Flow cytometric evaluation of S phase fraction may offer important prognostic
      information in patients with IPSID and could be useful in the clinical management
      of patients with this highly variable clinical syndrome. Further studies
      evaluating the value of DNA flow cytometry in larger groups of patients with
      IPSID are warranted.

PMID- 7529852
TI  - Angiogenesis in breast carcinoma--clinicopathologic relevance and potential use
      as a quantifiable surrogate endpoint biomarker.
AB  - Although stochastic acquisition of structural genetic aberrations has become the
      dominant paradigm for progression of solid tumors, the process of tumor cell
      invasion and metastasis in large part represents a cooperative interaction with
      host tissues. Such interactions occur at multiple levels and include the exchange
      of cytokines/growth factors, the induction of neovascularization (angiogenesis),
      proteolytic degradation and synthetic alterations of the native extracellular
      matrix, and fibroblast/inflammatory cell chemotaxis. Many classical histologic
      and mammographic features of breast carcinoma, such as desmoplasia, are a direct
      reflection of these tumor-host relationships. Further, sustained growth is not
      possible without a coordinated interaction between diverse neoplastic and native
      cell populations. In recent years, quantifiable parameters of tumor-host
      interaction, such as protease elaboration, have been shown to correlate with
      intrinsic properties of neoplastic cells and to predict clinical outcome. It is
      thus reasonable to propose that functional cellular alterations imposed by
      chemopreventive agents may be reflected in tumor-host interaction parameters. The
      objective of this review is to briefly summarize the literature addressing one
      parameter of tumor-host interaction--angiogenesis--emphasizing its applicability
      as a quantifiable biomarker in breast neoplasia.

PMID- 7529851
TI  - Usefulness of platelet-derived growth factor as a prognostic factor in pulmonary
      adenocarcinoma.
AB  - Platelet-derived growth factor (PDGF) in the resected pulmonary adenocarcinoma
      tissue of 88 patients was detected immunohistochemically by the avidin-biotin
      peroxidase technique to determine whether or not it is a prognostic parameter.
      The 88 patients were divided into PDGF (-) and PDGF (+) groups according to the
      stainability of the factor. The PDGF (-) group included 39 patients and the PDGF
      (+) group 49. The 5-year survival rate was 53% for the PDGF (-) group and 17% for
      the PDGF (+) group (P < 0.01). These findings indicate that the stainability of
      PDGF can be a prognostic parameter for pulmonary adenocarcinoma.

PMID- 7529853
TI  - Biomarkers associated with prostate cancer progression.
AB  - In search of biomarkers that predict of human prostate cancer progression, we
      hypothesized that these markers must be expressed in prostatic epithelial cells
      during multi-step prostate carcinogenesis. Since both genetic and epigenetic
      factors have been implicated in human prostate cancer development, two osseous
      metastatic experimental models were developed in our laboratory, one based on
      gene transfection and the other on stromal-epithelial interaction studies. In the
      genetic model, PC-3 cells transfected with point-mutated c-erbB-2/neu oncogene
      subsequently acquired the potential to metastasize from the prostate to soft
      tissues and the skeleton. In the epigenetic model, sublines derived from the
      parental androgen-dependent LNCaP cell line metastasized from the primary tumor
      to the lymph node and bone. Cells with known lineage relationships were cloned
      from both the primary and the metastatic tumors and were characterized
      extensively using cellular, biochemical, immunohistochemical, and molecular
      techniques. Relevant stage-specific biomarkers associated with prostate cancer
      progression in these two models were defined and used to evaluate human prostate
      tissues obtained from the clinic. In this communication, we focused our
      discussion on the potential importance of c-erbB-2/neu oncogene, vimentin,
      hepatocyte growth factor/scatter factor and its receptor, c-met oncogene, tumor
      angiogenesis and neuroendocrine factors as biomarkers for human prostate cancer
      progression.

PMID- 7529855
TI  - DNA ploidy in prostate cancer: potential measurement as a surrogate endpoint
      biomarker.
AB  - Measurements of DNA ploidy have considerable promise for serving as surrogate
      endpoint biomarkers (SEBs) for prostate carcinoma. Studies of benign prostatic
      hypertrophy (BPH) tissue by flow cytometry (FCM), image analysis, and fluorescent
      in situ hybridization (FISH) for ploidy invariably show normal DNA content and
      chromosome numbers. In contrast, most aggressive prostate cancers are aneuploid,
      particularly when new, sensitive methodologies are applied. Certain tumors which
      have appeared to be DNA diploid by FCM can be shown to be aneuploid with only one
      or a few abnormal chromosomes by FISH studies. Certain cases of prostatic
      intraepithelial neoplasia (PIN) are also known to be aneuploid by FISH ploidy
      using alpha satellite probes for centromere counting. The latest data suggest
      abnormalities of chromosomes 7 and 8 are most frequently detected. Therefore, a
      surrogate endpoint assay which detects aneusomies of chromosomes 7 or 8 in
      histologically normal or dysplastic prostate tissue might serve as a very
      significant intermediate endpoint biomarker to identify neoplastic prostate cells
      on their way to becoming clinically aggressive prostate carcinomas.

PMID- 7529854
TI  - Putative preneoplastic foci in the human prostate.
AB  - Our knowledge of prostate cancer is less well-defined than our knowledge of
      cancers of other organs. In the colon, for example, morphological criteria to
      identify carcinomas in situ and some putative preneoplastic lesions are clear;
      phenotypic differences in the expression of enzymes and antigens are documented
      in experimental models and are starting to be defined in humans. Experimental
      models of cancer of the liver and colon show evidence that "enzyme-altered foci"
      are preneoplastic. In these organs, the "normal" context is much clearer than in
      the prostate. In contrast, in the prostates of men in the same age range as those
      who develop prostate cancer, morphological aberrations are almost always present,
      diverse, and poorly understood. Murphy and Gaeta said that, "in the study of
      prostatic disease..., almost every aspect remains controversial...[and].... many
      of the 'known facts' concerning prostatic disease are poorly documented..." While
      being aware that the definitions of all benign and malignant lesions of the
      prostate are based on complex morphological criteria which must form the
      contemporary context for comparisons, our laboratory is searching for markers
      that will permit the identification of putative preneoplastic lesions in the
      prostate. In our opinion, these changes will not be found most efficiently, if
      they are present at all, in long established cell lines, advanced carcinomas, or
      serially transplantable xenografts of primary prostatic carcinomas. Our
      preliminary data suggest that several enzyme histochemical and
      immunohistochemical approaches are worthy of study. Markers that show promise
      include acid phosphatase, 5'-nucleotidase, leucine aminopeptidase, and
      CD44.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529856
TI  - Quantitative nuclear morphometry, Markovian texture descriptors, and DNA content
      captured on a CAS-200 Image analysis system, combined with PCNA and HER-2/neu
      immunohistochemistry for prediction of prostate cancer progression.
AB  - One hundred and twenty-four localized prostate cancer patients operated on at
      Johns Hopkins Hospital (JHH) since 1975 were identified. The sample was optimized
      for evaluation of prostate cancer progression. Based upon accurate clinical
      histories, these radical prostatectomy patients included 50 progressors and 74
      non-progressors using appearance of serum PSA as an indication of recurrence
      (mean follow-up = 8.6 +/- 1.8 years, range 7-15 years). All patients included in
      the study had no involvement of their seminal vesicles or lymph nodes at the time
      of prostatectomy. Average time to progression was 3.6 +/- 2 years, range of 1-8
      years. Using paraffin-embedded specimens, several five micron sections were cut
      and placed on Probe-On slides; one slide was H&E-stained and the other was
      Feulgen-stained. The H&E and Feulgen-stained slides were screened and "dotted" by
      pathologists at JHH and CytoDynostics, Inc. A CAS-200 Image analysis system (Cell
      Image Systems, Elmhurst, IL) equipped with a Cell Measurement Program version 1.2
      beta, was used to capture the Feulgen-stained images and to perform the
      calculations. From the "dotted" areas, 150 cancer cells were selected for
      measurement of DNA content and 27 nuclear morphometric shape and size factors,
      including 21 Markovian chromatin texture variables. Additional sections were used
      for immunochemistry staining with an alkaline phosphatase streptavidin-biotin
      complex stain to detect and quantitate cancer cells binding monoclonal antibodies
      directed against proliferating cell nuclear antigen (PCNA) and HER-2/neu antigen.
      All data were entered into a statistical program (STATA) for further analysis and
      univariate and multivariate statistical analysis was performed using logistic
      regression and its stepwise variant. The biomarkers of greatest utility to detect
      progressors when analyzed univariately included post-operative Gleason score (p =
      < 0.0001), HER-2/neu antigenicity (p = 0.0147), CAS-200 DNA ploidy (p = 0.008),
      and twelve Markovian nuclear texture and shape features (p = < 0.0001), whereas
      PCNA (p = 0.160) failed. The optimal set of nuclear morphometry progression tumor
      features were selected using backward stepwise logistic regression estimate
      analysis which drops variables due to collinearity. Although post-operative
      Gleason score is a strong univariate predictor of progression, DNA ploidy and HER
      2/neu contributed significantly to further stratification of higher risk groups
      within the low Gleason score subpopulation. The best Markovian features combined
      with post-operative Gleason score generated sensitivity = 90%, specificity = 96%,
      positive predictive value = 94%, negative predictive value = 93% and the area
      under the receiver operator curve was 0.975.

PMID- 7529857
TI  - The most promising surrogate endpoint biomarkers for screening candidate
      chemopreventive compounds for prostatic adenocarcinoma in short-term phase II
      clinical trials.
AB  - Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention
      trials to avoid the excessively long study periods and high costs associated with
      the use of cancer incidence reduction as an endpoint, particularly with
      relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be
      directly associated with the evolution of neoplasia, and develop with high
      frequency in abnormal cells of susceptible individuals. If SEBs can be modified
      by a particular intervention regimen in short-term studies, the rationale for
      carrying out long-term studies may be strengthened. The consensus panel
      identified a small and manageable group of biomarkers measured in tissue or serum
      as the most promising in prostate cancer chemoprevention, including (1) prostate
      specific antigen (PSA); (2) morphometric markers, such as nuclear size and
      roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) nuclear DNA
      content (ploidy); (5) oncogene c-erbB-2 (HER-2/neu) expression; (6) angiogenesis;
      and (7) high-grade prostatic intraepithelial neoplasia (PIN). Information
      regarding many of these and other biomarkers is limited, calling for further
      investigation. Also, these factors, chosen chiefly for their proven or proposed
      utility as prognostic factors, may be less useful as SEBs. It was agreed that
      concurrent study of numerous markers rather than single markers allows comparison
      of their relative utility, including assessment of ease of quantitation and the
      sensitivity, specificity, and positive and negative predictive value.

PMID- 7529858
TI  - Electrophysiological properties of substantia gelatinosa neurones in a novel
      adult spinal slice preparation.
AB  - A novel longitudinal spinal cord slice prepared from adult rats aged 3-6 weeks is
      described. This preparation differs from conventional slices in that it retains
      multiple dorsal roots, each more than 10 mm in length, and presents a sagittal
      section through the laminae of the dorsal and ventral horns. The substantia
      gelatinosa can be visually distinguished from the other laminae of the dorsal
      horn, thus making the preparation particularly suited for the study of neurones
      located in this region. Extracellular recordings were made from 142 substantia
      gelatinosa cells, most of which responded to electrical stimulation of a dorsal
      root. Using measurements of latency it was possible to estimate conduction
      velocities for afferent input fibres. The effects of iontophoretically applied
      excitatory amino acids and of tachykinin peptides on spontaneous and afferent
      evoked firing are briefly described. The preparation has applications in the
      investigation of mechanisms of primary afferent transmission within the dorsal
      horn and of transmission of afferent input between successive spinal segments.

PMID- 7529859
TI  - Assessment of long-term effects of transient anoxia on metabolic activity of rat
      hippocampal slices using triphenyltetrazolium chloride.
AB  - Hippocampal slices maintained in an oxygen-rich static interface chamber remained
      viable, as determined by the mitochondrial marker 2,3,5-triphenyltetrazolium
      chloride (TTC), for over 20 h in vitro. By contrast, slices exposed, after 1 h in
      vitro, to an anoxic environment for 25 min and then allowed to recover for 1-18
      h, showed an initial slight decrease in TTC staining followed by a dramatic
      decrease at time points greater than 6.5 h after anoxia. These data are
      suggestive of delayed neuronal death. Furthermore, the decreases in TTC staining
      induced by anoxia could be prevented by conditions known to prevent cell death
      either in vitro or in vivo. For example, pretreatment of the slices with the N
      methyl-D-aspartate antagonist 3-((RS)-2-carboxy-piperazin-4-yl)-propyl-1-
      phosphonic acid dose-dependently prevented the loss of TTC staining induced by 25
      min anoxia. In addition, high-intensity TTC staining correlated with normal CA1
      synaptic activity, even after more than 20 h in vitro, suggesting that TTC
      staining reflects functional neuronal activity. These data suggest that the use
      of TTC staining of in vitro hippocampal slices may represent a novel and
      convenient screen for anti-ischemic compounds.

PMID- 7529861
TI  - Hepatitis C virus.

PMID- 7529860
TI  - Aged lymphocyte proliferation following incorporation and retention of dietary
      omega-3 fatty acids.
AB  - T cell activation involves events at the plasma membrane; therefore, molecules
      such as long chain omega-3 fatty acids that alter the structure of the plasma
      membrane may affect the activation of aged T cells. In this project we
      investigated whether the incorporation of omega-3 fatty acids (from fish oil), in
      the presence of vitamin E, improves age-diminished T cell proliferation. Young
      and old mice were fed diets rich in either fish (menhaden) oil or saturated fat
      for various lengths of time. Splenocytes were harvested from these mice and
      stimulated in culture with either mitogen or the antigen keyhole limpet
      hemocyanin (for a secondary response); proliferation was estimated by
      [3H]thymidine incorporation. We found no discernible effect of dietary omega-3
      fatty acids (with vitamin E supplementation) on lymphocyte proliferation
      stimulated by the mitogens concanavalin A or phytohemagglutinin. We did, however,
      find that the saturated fat diet and the menhaden oil diet in young mice lowered
      protein kinase C activities in the particulate fractions of spleen cells when
      compared to chow-fed mice. Middle-aged and old mice were less affected by the
      experimental diets than young mice, but they demonstrated decreased protein
      kinase C activity as well. These alterations did not affect the ability of
      splenocytes to respond to mitogenic stimulation. Fatty acid analysis revealed
      that lymphocytes from mice fed saturated fat for 8.5 months retained significant
      amounts of the omega-3 fatty acid docosahexaenoic acid, despite the lack of
      dietary omega-3 fatty acids. However, when aged (but not young) lymphocytes were
      clonally expanded by antigen in vivo in the presence of dietary omega-3 fatty
      acids, they produced a greater secondary proliferative response than old
      lymphocytes expanded during a saturated fat diet. Although our results suggest
      that omega-3 fatty acids may enhance aged lymphocyte proliferation, the tenacious
      retention of these fatty acids makes comparison with omega-3-depleted lymphocytes
      difficult.

PMID- 7529862
TI  - Plague in India.

PMID- 7529863
TI  - Changes in plasma concentrations of vasoactive neuropeptides in patients with
      sepsis and septic shock.
AB  - The aim of this work was to study the hypothesis that the release of vasoactive
      neuropeptides may be related to the hemodynamic changes and severity of disease
      in human sepsis and septic shock. Twenty-two patients diagnosed with sepsis and
      treated in medical wards with standard supportive therapy and twenty patients
      admitted to a medical intensive care unit because of septic shock were studied
      Twenty healthy volunteers in a similar age range were enrolled as control group.
      Blood samples were taken at onset and every 12 hours on the following day after
      hospital admission to measure plasma concentrations of calcitonin gene-related
      peptide (CGRP), neuropeptide Y (NPY) and substance P (SP). Clinical and
      biochemical variables were measured simultaneously. The Acute Physiology and
      Chronic Health Evaluation (APACHE) II score was calculated on admission. From the
      day of admission, septic shock patients had significantly higher plasma CGRP-like
      immunoreactivity levels than patients with sepsis, as well as both groups of
      patients compared to control subjects. Plasma NPY-like immunoreactivity levels in
      patients with either sepsis or septic shock was significantly increased, and
      plasma SP-like immunoreactivity levels significantly reduced compared to those in
      controls. Plasma CGRP levels at study entry correlated with the APACHE II score
      (r = 0.71, p < 0.01), as well as with the cardiac index (r = 0.61, p < 0.05) and
      systemic vascular resistance index (r = -0.62, p < 0.05). Our data suggest that
      both CGRP and NPY, but not SP, are increasedly released into the circulation
      during the development of human sepsis and septic shock. In patients with sepsis
      the vasoconstriction mediated by the release of NPY appears to counterbalance the
      vasodilatory effect of CGRP. In septic shock patients, however, the release of
      NPY might be inadequately low to overcome the widespread CGRP-induced
      vasodilation.

PMID- 7529864
TI  - In vitro characterization of the non-peptide tachykinin NK1 and NK2-receptor
      antagonists, SR140333 and SR48968 in different rat and guinea-pig intestinal
      segments.
AB  - We investigated the potent non-peptide tachykinin receptor antagonists SR140333
      and SR48968 for their ability to prevent the contraction of isolated intestinal
      tissues elicited by the non-selective agonists substance P (SP) and neurokinin A
      (NKA), or by [Sar9,Met(O2)11]SP and [beta-Ala8]NKA-(4-10) that are selective
      agonists for NK1 and NK2 receptors, respectively. In guinea-pig ileum, containing
      mainly NK1-receptors: SR140333 caused a pseudo-irreversible blockade of
      contractions induced by either SP (KB, 0.01 nM) or [Sar9,Met(O2)11]SP (KB, 0.03
      nM); SR140333 but not SR48968, dose-dependently (IC50, 0.06 nM) antagonized the
      contractions elicited by capsaicin. In rat duodenum, containing mainly NK2
      receptors, SR48968 caused a parallel rightward shift of the concentration
      response curves of [beta-Ala8]NKA-(4-10) (pA2, 9.5), but not of NKA. In rat
      esophageal tunica muscularis mucosae, SR48968 non-competitively antagonized [beta
      Ala8]NKA-(4-10) and NKA. SR48968 and SR140333 thus appear to be potent tachykinin
      receptor antagonists, selective for intestinal receptors respectively of the NK2
      and NK1 type. The results also suggest that rat esophagus might contain a NK2
      receptor subtype different from that of rat duodenum.

PMID- 7529866
TI  - Expression of exogenous proteins in mammalian cells with the Semliki Forest virus
      vector.

PMID- 7529865
TI  - HTLV-I associated cutaneous T-cell lymphoma--report of a case with atypical
      clinical presentation.
AB  - A case of a 20-years-old black man from Salvador, Bahia with HTLV-I associated T
      cell lymphoma is presented. In spite of the absence of splenomegaly and leukemia,
      the patient had a marked cephalic tumoral infiltration associated with axillary
      tumors in a pattern not yet described in adult T cell lymphoma. Peripheral blood
      involvement was observed later on in the course of the disease. The patient
      underwent chemotherapy but died seven months after diagnosis.

PMID- 7529867
TI  - Recombinant Sindbis virus as an expression system for cell biology.

PMID- 7529868
TI  - Recombinant Rous sarcoma virus vectors for avian cells.

PMID- 7529871
TI  - Interaction of Shc with Grb2 regulates association of Grb2 with mSOS.
AB  - The adapter protein Shc has been implicated in Ras signaling via many receptors,
      including the T-cell antigen receptor (TCR), B-cell antigen receptor, interleukin
      2 receptor, interleukin-3 receptor, erythropoietin receptor, and insulin
      receptor. Moreover, transformation via polyomavirus middle T antigen is dependent
      on its interaction with Shc and Shc tyrosine phosphorylation. One of the
      mechanisms of TCR-mediated, tyrosine kinase-dependent Ras activation involves the
      simultaneous interaction of phosphorylated Shc with the TCR zeta chain and with a
      second adapter protein, Grb2. Grb2, in turn, interacts with the Ras guanine
      nucleotide exchange factor mSOS, thereby leading to Ras activation. Although it
      has been reported that in fibroblasts Grb2 and mSOS constitutively associate with
      each other and that growth factor stimulation does not alter the levels of
      Grb2:mSOS association, we show here that TCR stimulation leads to a significant
      increase in the levels of Grb2 associated with mSOS. This enhanced Grb2:mSOS
      association, which occurs through an SH3-proline-rich sequence interaction, is
      regulated through the SH2 domain of Grb2. The following observations support a
      role for Shc in regulating the Grb2:mSOS association: (i) a phosphopeptide
      corresponding to the sequence surrounding Tyr-317 of Shc, which displaces Shc
      from Grb2, abolished the enhanced association between Grb2 and mSOS; and (ii)
      addition of phosphorylated Shc to unactivated T cell lysates was sufficient to
      enhance the interaction of Grb2 with mSOS. Furthermore, using fusion proteins
      encoding different domains of Shc, we show that the collagen homology domain of
      Shc (which includes the Tyr-317 site) can mediate this effect. Thus, the Shc
      mediated regulation of Grb2:mSOS association may provide a means for controlling
      the extent of Ras activation following receptor stimulation.

PMID- 7529869
TI  - Heat shock protein HSP60 can alleviate the phenotype of mitochondrial RNA
      deficient temperature-sensitive mna2 pet mutants.
AB  - mna2, which belongs to the class I temperature-sensitive pet mutants that lose
      mitochondrial (mt)RNA at restrictive temperature, was shown by complementation
      and sequence determination to correspond to the gene coding for HSP60. Both mna2
      1 and mna2-2, the two available alleles of mna2, have conservative single amino
      acid substitutions in the HSP60 gene. Valine substitutes for an alanine (position
      47) in mna2-1, and an isoleucine substitutes for a valine (position 77) in mna2
      2. These substitutions result in defects in respiration and in steady-state mtRNA
      accumulation. Wild-type hsp60 alleviates the mtRNA phenotype completely, while
      partially relieving the respiratory deficiency.

PMID- 7529870
TI  - A gene proposed to encode a transmembrane domain of an ABC transporter is
      expressed in wheat mitochondria.
AB  - In a study of transcribed regions of the wheat mitochondrial genome, we
      identified an open reading frame of 720 bp, which was consequently designated
      orf240. The amino acid sequence deduced from orf240 shows a high level of
      similarity with HelC, a protein essential for c-type cytochrome biogenesis in the
      photosynthetic purple bacterium Rhodobacter capsulatus. HelC is part of a
      putative heme ABC transporter. An open reading frame homologous to orf240 is
      present in the mitochondrial genome of Marchantia polymorpha. The wheat gene is
      expressed as an mRNA of 2.8 kb, which is further processed to smaller
      transcripts. The transcript is highly edited, with 36 C to U modifications found
      in the coding region of all cDNAs sequenced. RNA editing is responsible for
      changes in 14% of the amino acids specified by the transcript.

PMID- 7529873
TI  - Effects of butyrate and glucocorticoids on gamma- to beta-globin gene switching
      in somatic cell hybrids.
AB  - Butyrate and its analogs have been shown to induce fetal hemoglobin in humans and
      primates and in erythroid cell cultures. To obtain insights concerning the
      cellular mechanisms of butyrate action, we analyzed the effects of butyrate on
      human globin gene expression in hybrids produced by fusing mouse erythroleukemia
      cells (MEL) with human fetal erythroid cells (HFE). These hybrids initially
      express human fetal hemoglobin but subsequently switch to adult globin expression
      after several weeks in culture. We found that alpha-aminobutyric acid, a butyrate
      analog which does not induce terminal maturation, strikingly delays the rate of
      the gamma- to beta-globin gene (gamma-to-beta) switch in the HFE x MEL hybrids.
      The effect of butyrate on globin expression is transient, with the result that
      the delay of globin gene switching requires the continuous presence of this
      compound in culture. Furthermore, butyrate fails to induce fetal hemoglobin
      expression in hybrids which have switched, suggesting that the effect of this
      compound on gamma-globin expression is due to inhibition of gamma gene silencing
      rather than to induction of gamma gene transcription. Since in other cellular
      systems, glucocorticoids antagonize the action of butyrate, the effect of
      dexamethasone on the gamma-to-beta switch in HFE x MEL hybrids was examined.
      Dexamethasone strikingly accelerated the gamma-to-beta switch, and its effect was
      irreversible. The effects of dexamethasone and butyrate on the gamma-to-beta
      switch of the HFE x MEL hybrids appear to be codominant. These results indicate
      that steroids can have a direct effect on globin gene switching in erythroid
      cells.

PMID- 7529872
TI  - Overexpressed Csk tyrosine kinase is localized in focal adhesions, causes
      reorganization of alpha v beta 5 integrin, and interferes with HeLa cell
      spreading.
AB  - The C-terminal Src kinase p50csk phosphorylates Src family tyrosine kinases and
      down-regulates their activity in vitro. To gain insight into the cellular
      functions of this potentially antioncogenic enzyme, we have overexpressed the csk
      cDNA by using an inducible promoter in HeLa cells. Despite some differences in
      basal Src activity in the clones analyzed, Src activity was not significantly
      suppressed, while the amount of p50csk and Csk activity increased at least 10
      fold during 3 days of induction. Immunofluorescence for the induced p50csk was
      localized in the cytoplasm and distinctly in focal adhesions, in which the amount
      of phosphotyrosine containing proteins was also increased. Point and deletion
      mutagenesis experiments showed that localization in focal adhesions was dependent
      on the SH2 and SH3 domains of Csk but not on its catalytic activity. Csk formed a
      complex with the focal adhesion protein paxillin in cells, and its SH2 domain was
      shown to interact with pp125FAK and paxillin in vitro. After Csk induction, the
      cells became spherical and more loosely attached to the culture substratum, and
      the alpha v beta 5 integrin complex (vitronectin receptor) of focal adhesions was
      redistributed to a novel type of structure consisting of punctate plaques on the
      ventral cell surface. These phenotypic changes occurred in several clones
      analyzed and were totally reversible when Csk was switched off, but they did not
      occur in cells overexpressing the catalytically inactive Csk R-222 mutant or
      luciferase. Our results thus show that a fraction of cellular Csk is targeted to
      focal adhesions via its SH2 and SH3 domains, probably interacting with tyrosyl
      phosphorylated focal adhesion proteins. They also suggest that Csk is involved in
      the regulation of integrins controlling cell attachment and shape.

PMID- 7529874
TI  - Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces
      association of BCR with GRB-2/SOS.
AB  - The human bcr gene encodes a protein with serine/threonine kinase activity,
      CDC24/dbl homology, a GAP domain, and an SH2-binding region. However, the precise
      physiological functions of BCR are unknown. Coexpression of BCR with the
      cytoplasmic protein-tyrosine kinase encoded by the c-fes proto-oncogene in Sf-9
      cells resulted in stable BCR-FES protein complex formation and tyrosine
      phosphorylation of BCR. Association involves the SH2 domain of FES and a novel
      binding domain localized to the first 347 amino acids of the FES N-terminal
      region. Deletion of the homologous N-terminal BCR-binding domain from v-fps, a
      fes-related transforming oncogene, abolished transforming activity and tyrosine
      phosphorylation of BCR in vivo. Tyrosine phosphorylation of BCR in v-fps
      transformed cells induced its association with GRB-2/SOS, the RAS guanine
      nucleotide exchange factor complex. These data provide evidence that BCR couples
      the cytoplasmic protein-tyrosine kinase and RAS signaling pathways.

PMID- 7529875
TI  - Identification and characterization of a neuroretina-specific enhancer element in
      the quail Pax-6 (Pax-QNR) gene.
AB  - Using nuclear run-on assays, we showed that the tissue-specific expression of
      quail Pax-6 (Pax-QNR) P0-initiated mRNAs is due in part to regulation of the gene
      at the transcriptional level. Regulatory sequences governing neuroretina-specific
      expression of the P0-initiated mRNAs were investigated. By using reporter-based
      expression assays, we characterized a region within the Pax-QNR gene, located 7.5
      kbp downstream from the P0 promoter, that functions as an enhancer in neuroretina
      cells but not in nonexpressing P0-initiated mRNA cells (quail embryo cells and
      quail retinal pigment epithelial cells). This enhancer element functioned in a
      position- and orientation-independent manner both on the Pax-QNR P0 promoter and
      the heterologous thymidine kinase promoter. Moreover, this enhancer element
      exhibited a developmental stage-specific activity during embryonic neuroretina
      development: in contrast to activity at day E7, the enhancer activity was very
      weak at day E5. This paralleled the level of expression of P0-initiated mRNAs
      observed at the same stages. Using footprinting, gel retardation, and
      Southwestern (DNA-protein) analysis, we demonstrated the existence of four
      neuroretina-specific nuclear protein-binding sites, involving multiple unknown
      factors. In addition we showed that the quail enhancer element is structurally
      and functionally conserved in mice. All of these results strongly suggest that
      this enhancer element may contribute to the neuroretina-specific transcriptional
      regulation of the Pax-6 gene in vivo.

PMID- 7529876
TI  - Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic
      domain regulates kinase activity: a role for Src family kinases.
AB  - Focal adhesion kinase (FAK) is a widely expressed nonreceptor protein-tyrosine
      kinase implicated in integrin-mediated signal transduction pathways and in the
      process of oncogenic transformation by v-Src. Elevation of FAK's phosphotyrosine
      content, following both cell adhesion to extracellular matrix substrata and cell
      transformation by Rous sarcoma virus, correlates directly with an increased
      kinase activity. To help elucidate the role of FAK phosphorylation in signal
      transduction events, we used a tryptic phosphopeptide mapping approach to
      identify tyrosine sites of phosphorylation responsive to both cell adhesion and
      Src transformation. We have identified four tyrosines, 397, 407, 576, and 577,
      which are phosphorylated in mouse BALB/3T3 fibroblasts in an adhesion-dependent
      manner. Tyrosine 397 has been previously recognized as the major site of FAK
      autophosphorylation. Phosphorylation of tyrosines 407, 576, and 577, which are
      previously unrecognized sites, is significantly elevated in the presence of c-Src
      in vitro and v-Src in vivo. Tyrosines 576 and 577 lie within catalytic subdomain
      VIII--a region recognized as a target for phosphorylation-mediated regulation of
      protein kinase activity. We found that maximal kinase activity of FAK immune
      complexes requires phosphorylation of both tyrosines 576 and 577. Our results
      indicate that phosphorylation of FAK by Src (or other Src family kinases) is an
      important step in the formation of an active signaling complex.

PMID- 7529880
TI  - Chromosomal damages by ethanol and acetaldehyde in Saccharomyces cerevisiae as
      studied by pulsed field gel electrophoresis.
AB  - We report on the effect of ethanol and acetaldehyde on yeast chromosomal DNA and
      on isolated DNA. Ethanol induced DNA single-strand breaks in repair deficient but
      not in repair proficient Saccharomyces cerevisiae. Acetaldehyde has a deleterious
      effect on chromosomal DNA in cells as well as on isolated DNA. The results
      presented support earlier data to show that ethanol is mutagenic via its first
      metabolite, acetaldehyde.

PMID- 7529878
TI  - Micronucleus formation induced by three polycyclic aromatic hydrocarbons in rat
      bone marrow and spleen erythrocytes following intratracheal instillation.
AB  - Benz[a]anthracene (BA), dibenz[a,h]anthracene (DBA) and dibenzo[a,i]pyrene (DBP)
      are polycyclic aromatic hydrocarbons (PAHs) found in incomplete combustion
      products of fossil fuels, coal tar, and other organic materials. Workers in
      related industries may be exposed to these chemicals by inhalation. The
      information related to the potential health hazards of these chemicals to the
      exposed workers, however, is very limited. In the present study, micronucleus
      (MN) formation in rat bone marrow and spleen polychromatic erythrocytes (PCEs)
      was determined following three intratracheal instillations within a 24-h period
      with either BA, DBA or DBP. Three doses with five rats per dose were used for
      each chemical. Bone marrow and spleen cells were harvested 24 h after the first
      dosing. Results showed that the order of toxicity for the three PAHs was DBP >
      DBA > BA. BA induced MN in a dose-related manner in both bone marrow and spleen
      PCEs at doses above 25 mg/kg. DBA caused significant increases in the frequencies
      of MN in both spleen and bone marrow PCEs at the dose of 8.5 mg/kg or higher. At
      10 mg/kg, DBP significantly increased MN frequency in spleen PCEs, but the
      increase in bone marrow PCEs was not significantly different from the control.
      These results indicate that: (1) all three PAHs studied are absorbed through the
      respiratory tract and their genotoxic metabolites reach the bone marrow and/or
      spleen; (2) except for DBP which does not induce MN in the bone marrow, all three
      PAHs induced MN in both bone marrow and spleen PCEs; and (3) the sensitivity of
      the spleen to the three PAHs is comparable to or higher than that of the bone
      marrow.

PMID- 7529877
TI  - Structure-function correlates of autoantibodies to nucleic acids. Lessons from
      immunochemical, genetic and structural studies.
AB  - Nucleic acid binding autoantibodies are the hallmark of the human autoimmune
      disease, systemic lupus erythematosus (SLE) and are also prevalent in mouse
      models of this disease. The immunologic stimuli for the production of these
      antibodies as well as their pathogenic mechanisms are not well understood.
      However, extensive immunochemical and genetic studies, together with initial
      crystallographic analysis and computer modeling, have suggested several structure
      function correlates which will form the basis for future research. The anti-DNA
      and anti-RNA autoantibodies comprise a continuous spectrum of specificities in
      which a delicate balance exists between the binding to the sugar-phosphate
      backbone and the interactions with the heterocyclic bases of the nucleic acid.
      Prominent in these interactions are the products of specific V-region
      immunoglobulin genes, some of which appear to be uniquely suitable for nucleic
      acid binding. Other structural elements encoded by D minigenes, N sequences and
      somatic mutations, help to increase the affinity of the binding interaction, and
      may also increase the repertoire of nucleic acid binding antibodies by combining
      with a relatively large number of additional V-gene products. Initial
      crystallographic analyses of anti-DNA antibodies indicate some fundamental
      differences in the structure and shape of ssDNA and dsDNA antibody combining
      sites. However, they also suggest a considerable degree of flexibility of both
      antibody and antigen, which is induced by their binding interaction.

PMID- 7529879
TI  - Comparison of effects of iron and calcium chelators on the response of L5178Y
      sublines to X-rays and H2O2.
AB  - The L5178Y murine lymphoma subline LY-R is twofold more resistant to killing by
      ionizing radiation than the subline LY-S. In contrast, LY-R cells are more
      sensitive to killing by hydrogen peroxide: at 37 degrees C LY-R cells are 1.4
      times more sensitive to the killing effect of H2O2 than LY-S cells. Pretreatment
      with the iron chelator desferroxamine followed by hydrogen peroxide treatment at
      37 degrees C gives a considerable sparing effect, which is substantially greater
      for the LY-R subline than for the LY-S subline. This is reflected in the initial
      DNA damage (estimated by single cell gel electrophoresis), survival and mutation
      frequency in the HGPRT locus. Similar results have been obtained with calcium
      chelators, which, according to recent findings (Sandstrom and Granstrom 1993),
      also are efficient iron chelators. In contrast, the response to X-rays is not
      modified by the above chelators, with the exception of mutation frequencies:
      lower mutant numbers are found in desferroxamine pretreated LY-R cells.

PMID- 7529881
TI  - Exposure of CHO cells to AluI: comparison of chromosomal aberrations and cell
      survival.
AB  - Chinese hamster ovary (CHO) cells were exposed to various doses of the
      restriction endonuclease AluI in the presence of 2.2 M glycerol. Some of the
      cells were cultured for analysis of chromosomal aberrations and some for analysis
      of colony-forming ability. Cell killing is mainly mediated by chromosomal
      aberrations.

PMID- 7529882
TI  - Spectra of superoxide-induced mutations in the lacI gene of a wild-type and a
      mutM strain of Escherichia coli K-12.
AB  - We have analyzed the spectra of superoxide-induced mutations in the chromosomal
      lacI gene of a wild-type and a mutM strain of Escherichia coli K-12. The mutM
      strain is known to be deficient in removing 8-hydroxyguanine from DNA. An
      intracellular superoxide-generating agent, menadione, was used to cause the
      mutation. Analysis of the mutated DNA showed marked differences between the
      mutants from the wild type and those from the mutM strain. In the mutants from
      the wild type, all possible base-pair substitutions were present and their
      proportions were similar to each other, whereas in those from the mutM bacteria
      there was a 90% bias in favor of transversion. Furthermore, in the mutM strain GC
      to-CG transversion rather than GC-to-TA was predominantly induced. 64% of the GC
      to-CG transversions in the mutM strain occurred at the site of (CT/GC)GGC
      (mutated base underlined). The favorable mutation site, CTGGC, was the same as
      that of the UV- and sunlight-induced mutations previously reported: the mutations
      observed there were also G-to-C transversions. We speculate from these results
      that the superoxide in the cells may lead to production of a modified guanine
      that can pair with guanine and is subject to removal by the MutM protein.

PMID- 7529883
TI  - Chromosome analysis of human spermatozoa exposed to antineoplastic agents in
      vitro.
AB  - We studied in vitro the cytogenetic effects of six antineoplastic agents,
      bleomycin (BM), cyclophosphamide (CP), daunomycin (DM), methyl methanesulfonate
      (MMS), mitomycin C (MMC) and triethylenemelamine (TEM) on spermatozoa, using an
      interspecific in vitro fertilization system between zona-free hamster oocytes and
      human or bull spermatozoa. In preliminary experiments with bull spermatozoa,
      clastogenic effects were clearly shown with BM, DM, MMS and TEM, but not with CP
      and MMC. In main experiments, the effects of the first four chemicals were
      studied in detail with human spermatozoa. Total numbers of 585 and 512
      spermatozoa were karyotyped in the control and the chemical-treated groups
      respectively. The incidence of spermatozoa with structural chromosome aberrations
      was 34.5%, 53.0%, 59.3%, and 55.6% in the BM (50 micrograms/ml, 90 min), DM (0.1
      microgram/ml, 90 min), MMS (100 micrograms/ml, 120 min) and TEM (0.1
      micrograms/ml, 120 min) groups respectively, each showing a significantly higher
      incidence than the matched controls (10.1-13.5%). Breakage-type aberrations were
      more frequent than exchange-type aberrations in the BM, MMS and TEM groups, while
      the exchange-type aberrations were more frequent in the DM group. Exchanges were
      mainly of the chromatid type in the DM, MMS and TEM groups, while chromosome-type
      exchanges occurred more frequently in the BM group. These results are discussed
      in relation to previous data on chemical-induced chromosome aberrations in
      mammalian somatic cells and in mouse spermatozoa.

PMID- 7529885
TI  - Genotoxicity of trans-anethole in vitro.
AB  - Trans-anethole genotoxicity has been evaluated previously both in vitro and in
      vivo. To ascertain the reproducibility and relevance of previously conducted gene
      mutation studies, the Salmonella/microsome test and the L5178Y mouse lymphoma
      TK+/- assay were repeated according to the protocols that previously produced
      positive results. For the mouse lymphoma TK+/- assay, standard conditions were
      employed. For the Salmonella/microsome tests, however, metabolic cofactors were
      supplemented relative to standard protocols. In addition, trans-anethole was
      evaluated for its ability to induce chromosome aberrations in vitro in Chinese
      hamster ovary cells. The results presented here indicate that trans-anethole does
      not increase the mutant frequency in the Salmonella/microsome test, whereas a
      dose-related response was confirmed in the L5178Y mouse lymphoma TK+/- assay with
      metabolic activation. The metabolic conditions used in each of the published gene
      mutation assays may explain the various responses to trans-anethole. Trans
      anethole did not induce chromosome aberrations in Chinese hamster ovary cells.
      The molecular nature of the genetic change induced in mouse lymphoma cells by
      trans-anethole has not been identified but the available genotoxicity data are
      consistent with either a recombination event or a non-DNA reactive mechanism.
      Considering the trans-anethole genotoxicity data base as a whole, including the
      positive response observed only in the L5178Y mouse lymphoma TK+/- assay, the
      irreproducible response in the Salmonella/microsome test, the negative result in
      the chromosome aberration test in vitro and the results from 32P-postlabeling
      studies in vivo, as well as the occurrence of liver tumors in the rat bioassay
      only at doses which exceeded the MTD and caused significant liver toxicity,
      repeated toxic insult followed by compensatory cell proliferation is favored as
      an underlying mechanism for the observed rat tumorigenic response.

PMID- 7529886
TI  - Genetic control of RBE of alpha-particles for yeast cells irradiated in
      stationary and exponential phase of growth.
AB  - Survival curves of S. cerevisiae wild type and rad 50, 51, 52 and 54 mutants in
      haploid and diploid strains were measured after gamma-ray and alpha-particle
      irradiation in stationary and exponential phase of growth. The values of RBE of
      high-LET radiation, defined as the ratio of the mean lethal doses after sparsely
      and densely ionizing radiations, were determined. A correlation between the RBE
      of alpha-particles and cell repair capacity was supported for stationary phase
      cultures. For the first time, it was shown for all strains studied that at
      exponential phase of growth the RBE of alpha-particle-induced survival was
      decreased in comparison with that for stationary cells. For most mutant cells RBE
      was close to unity, i.e. cell radiosensitivity was almost identical for both
      sparsely and densely ionizing radiation. Possible reasons for the observed
      radiation responses are discussed.

PMID- 7529884
TI  - Sister-chromatid exchanges in lymphocytes from methimazole-induced hypothyroid
      mice.
AB  - The inhibitory effect of an antithyroid drug on mouse T lymphocytes was
      investigated. Inbred C57BL/6 mice were provided with an antithyroid drug,
      methimazole, for 2, 4 and 6 weeks and the in vitro responses of the lymphocytes
      were studied. The proliferative responses of T lymphocytes from the spleen of
      methimazole (MMI)-treated mice significantly (p < 0.05) decreased following
      concanavalin A stimulation, and the inhibitory effect became prominent with the
      increased duration of MMI treatment. A concomitant increase in the frequency of
      induced sister-chromatid exchanges was also observed in these T lymphocytes. When
      the splenocytes were stimulated with concanavalin A for 24 h, their ability to
      produce interleukin-2 (IL-2) was significantly decreased (p < 0.05). The results
      indicated that methimazole interfered with the normal proliferation of T
      lymphocytes by suppressing the production of IL-2, a cytokine also known as T
      cell growth factor, as well as inducing a higher incidence of sister-chromatid
      exchange during cell division.

PMID- 7529887
TI  - Screening of tea clones for inhibition of PhIP mutagenicity.
AB  - Standard black and green tea extracts have been known to inhibit mutagenicity
      caused by PhIP, in the Salmonella typhimurium TA98 assay containing S9 fraction
      from the liver of rats induced with alpha-naphthoflavone and phenobarbital.
      Breeding and selection programs for high yielding tea clones have successfully
      increased yields in many tea producing areas. Six clonal teas and three seedling
      teas were obtained from a tea producing area in Southern Africa. Standard black
      and green teas were used as controls. Dose-dependent inhibition of the bacterial
      mutagenicity elicited by two concentrations of PhIP was found in the extracts of
      all the teas tested. This indicates that the clonal teas have not lost their anti
      mutagenic properties. Small differences were found amongst the clonal teas in
      their ability to inhibit mutagenicity. This indicates that it may be possible to
      enhance this trait in future breeding and selection programs.

PMID- 7529888
TI  - Streptozotocin-induced chromosomal aberrations, SCEs and mutations in CHO-9
      parental cells and in EM-C11 mutant cell line.
AB  - The genotoxic effects induced by the monofunctional nitrosourea derivative
      streptozotocin (STZ) were investigated in Chinese hamster ovary cells, parental
      (CHO-9) and its mutant hypersensitive to alkylating agents, designated EM-C11.
      The ability of this compound to induce chromosomal aberrations, cell killing,
      sister-chromatid exchanges (SCEs) and mutations was evaluated on these two cell
      lines. The mutant cells were found to be slightly more sensitive to the killing
      effects of STZ than the parental cell line. EM-C11 cells also showed higher
      levels of STZ-induced chromosomal aberrations than CHO-9 cells, but appeared to
      be equally sensitive to induction of SCEs. The frequencies of STZ-induced
      mutations, measured as resistant Na+/K(+)-ATPase and HPRT mutants, revealed a
      higher sensitivity of EM-C11 to the mutagenic effects of this compound.

PMID- 7529890
TI  - Anti-mutagenic agents are also co-recombinogenic and co-mutagenic agents are also
      anti-recombinogenic.

PMID- 7529889
TI  - Detection of bulky DNA lesions in the liver of patients with Wilson's disease and
      primary haemochromatosis.
AB  - In the human metal storage disorders of Wilson's disease and primary
      haemochromatosis, ion transport and excretion dysfunctions result in the
      intracellular deposition of copper and iron, respectively. These aberrant
      accumulations of transition metal ions lead to extensive tissue damage,
      especially in the liver. In order to investigate the possible role of metal ion
      mediated oxygen free radical-generated DNA damage in these processes, DNA was
      isolated from liver of eight Wilson's disease patients and six haemochromatosis
      patients. Significant levels of bulky DNA damage were detected in these samples
      by 32P-postlabelling analysis, but were not found in liver DNA from age-matched
      controls. This form of novel DNA damage was detected in six out of eight Wilson's
      patients, varying between approximately 1 and 100 base modifications per 10(8)
      nucleotides, and in all of the haemochromatosis samples examined; the levels of
      modified species per 10(8) nucleotides varying from approximately 2 to 50. HPLC
      analysis of these bulky DNA lesions demonstrated that the species formed in
      Wilson's disease and in haemochromatosis were chromatographically identical but
      were not the same as putative purine dimers that can be generated in DNA by in
      vitro incubation with Cu+/Fe2+ and H2O2 (although the possibility that the
      adducts detected are closely related has not been ruled out). Analysis of the
      oxidative base lesion 8-hydroxydeoxyguanosine showed that levels were not
      elevated in liver DNA from either Wilson's disease or haemochromatosis sufferers.
      In fact, a statistically significantly lower level of this lesion was found in
      Wilson's disease patients than in controls. These data suggest that bulky DNA
      damage present in the liver of both wilson's disease and primary haemochromatosis
      patients may play a more important role in the induction of tissue damage than 8
      hydroxydeoxyguanosine. The novel DNA damage detected by 32P-poslabelling may also
      be a significant factor in the initiation of neoplasia leading to malignant
      hepatoma in haemochromatosis patients.

PMID- 7529891
TI  - Identification of macrophages in the muscle biopsy preparations: a comparative
      study using specific monoclonal antimacrophage antibodies and acid phosphatase
      reaction.

PMID- 7529892
TI  - Brief report: uveitis caused by Tropheryma whippelii (Whipple's bacillus)

PMID- 7529893
TI  - The diagnosis of Whipple's disease.

PMID- 7529894
TI  - Bartonella (Rochalimaea) quintana endocarditis in three homeless men.
AB  - BACKGROUND: Bartonella (Rochalimaea) quintana is the agent of trench fever and is
      transmitted by the body louse. We searched for this organism in three alcoholic
      homeless men with endocarditis. METHODS: Blood samples were cultured on a human
      endothelial cell line and on blood agar. Bacteria were identified by sequencing
      the amplified 16S ribosomal RNA gene. The presence of bartonella in tissue was
      assessed by Gram's staining, immunostaining, and polymerase-chain-reaction
      amplification. Serologic studies for antibodies to bartonella species were
      performed by indirect immunofluorescence and Western immunoblotting. RESULTS: B.
      quintana was isolated from one patient in the blood-agar culture and from the
      other two patients in the endothelial-cell culture. The organism was also
      identified by both immunostaining and molecular techniques in the valvular
      vegetations from the three patients and in a cervical lymph node from one
      patient. The 16S ribosomal RNA gene sequences of the three isolates were almost
      identical to that of the prototype strain of B. quintana. High titers of
      antibodies to B. quintana were detected in all three patients, but so were cross
      reacting antibodies to chlamydia species. In all three patients studies were
      repeatedly negative for antibodies to the human immunodeficiency virus.
      CONCLUSIONS: B. quintana is a cause of endocarditis in homeless patients and may
      be serologically misdiagnosed as a chlamydial infection.

PMID- 7529895
TI  - Bartonella (Rochalimaea) quintana bacteremia in inner-city patients with chronic
      alcoholism.
AB  - BACKGROUND: Bartonella (Rochalimaea) quintana is a fastidious gram-negative
      bacterium known to cause trench fever, cutaneous bacillary angiomatosis, and
      endocarditis. Between January and June 1993 in Seattle, we isolated B. quintana
      from 34 blood cultures obtained from 10 patients not known to be infected with
      the human immunodeficiency virus (HIV). METHODS: After identifying the isolates
      as B. quintana by direct immunofluorescence and DNA-hybridization studies, we
      determined strain hybridization with studies of restriction-fragment-length
      polymorphisms (RFLPs) of the intergenic spacer (noncoding) region of ribosomal
      DNA amplified by the polymerase chain reaction (PCR). To characterize the
      epidemiologic and clinical features of bartonella infections in these patients,
      we performed a retrospective case-control study using as controls 20 patients
      with blood cultures obtained at approximately the same time as those obtained
      from the index patients. RESULTS: B. quintana isolates from the 10 patients were
      indistinguishable by PCR-RFLP typing. All 10 patients had chronic alcoholism, and
      8 were homeless (P = 0.001 for both comparisons with controls). The six patients
      who underwent HIV testing were seronegative. At the time of their initial
      presentation, seven patients had temperatures of at least 38.5 degrees C. Six
      patients had three or more blood cultures that were positive for B. quintana, and
      in four of these patients B. quintana was isolated from blood cultures obtained
      10 or more days apart. Subacute endocarditis developed in two patients and
      required surgical removal of the infected aortic valve in one of them. Nine
      patients recovered; one died of sepsis from Streptococcus pneumoniae infection.
      CONCLUSIONS: B. quintana is a cause of fever, bacteremia, and endocarditis in HIV
      seronegative, homeless, inner-city patients with chronic alcoholism.

PMID- 7529896
TI  - Has trench fever returned?

PMID- 7529897
TI  - Neurokinin B gene expression is increased in the arcuate nucleus of
      ovariectomized rats.
AB  - Hypertrophy and increased gene expression of tachykinin neurons occur in the
      infundibular (arcuate) nucleus of postmenopausal women. We have hypothesized that
      the alterations in tachykinin gene expression in the hypothalami of
      postmenopausal women are secondary to ovarian failure and not due to age per se.
      In this study, in situ hybridization and computer-assisted microscopy were used
      to determine whether ovariectomy modulates neurokinin B (NKB), substance P (SP)
      or proopiomelanocortin (POMC) gene expression in the rat arcuate nucleus. Four
      groups were examined: proestrus; diestrous day 1; ovariectomized, and constant
      estrus induced by a single injection of 20 mg/kg estradiol valerate. Rats were
      sacrificed 2 months after treatment. Computer-assisted microscopy was used to
      determine the number of tachykinin neurons, cell areas, and the autoradiographic
      grain density of labeled neurons. We report marked changes in NKB gene expression
      in ovariectomized rats. The number of neurons containing NKB gene transcripts was
      significantly greater in ovariectomized rats (16.9 +/- 1.0 neurons/arcuate
      section) than all other groups. There was also a significant difference in the
      number of NKB neurons/arcuate section between proestrous (8.9 +/- 1.8 neurons)
      and diestrous (4.8 +/- 1.0 neurons) rats. The lowest number of neurons was
      detected in the estradiol valerate-injected rats (2.9 +/- 0.6 NKB neurons/arcuate
      section). Furthermore, the autoradiographic grain density of NKB neurons was
      doubled in the ovariectomized group compared to all other groups. In contrast,
      few SP neurons were identified in the rat arcuate nucleus and no changes were
      detected during the estrous cycle or in response to ovariectomy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7529898
TI  - Pituitary-dependent hormonal regulation of galaninergic neurons in the rat
      hypothalamus.
AB  - To investigate whether pituitary-dependent hormones may regulate galanin (GAL)
      content, synthesis and distribution in the hypothalamus, female hypophysectomized
      Wistar rats were treated for 2 weeks with subcutaneous injections of thyroxine
      (T4, 2 x 1 microgram), bovine growth hormone (GH, 2 x 125 micrograms), cortisol
      (C, 50 micrograms), subcutaneous implants of beta-estradiol (E2, 5-mm implant,
      dilution 1:1), or with the combinations [T4+GH], [T4+GH+C+E2] or [T4+GH+C+E2 +
      rat PRL, 2 x 125 micrograms] (doses/100 g BW/day). Concentrations of GAL in the
      hypothalamus were measured by radioimmunoassay (RIA) and GAL mRNA abundance was
      quantified by Northern blot (6 rats/group); 2 rats/group were used for
      immunohistochemistry. Hypophysectomy caused decreases of hypothalamic GAL peptide
      and mRNA concentrations (by 70 and 50%, respectively; p < 0.05 vs. intact rats).
      GAL immunoreactivity disappeared in the median eminence (ME), but increased in
      the neurohypophyseal magnocellular neurons of hypophysectomized rats.
      Substitution with T4, GH, [T4+GH], C or E2 had no significant effect on total
      hypothalamic GAL peptide and GAL mRNA concentrations. A treatment combining
      [T4+GH+C+E2] increased hypothalamic GAL (1.9 +/- 0.1 vs. 1.2 +/- 0.1 ng/mg
      protein in untreated hypophysectomized rats; p < 0.01) and GAL mRNA
      concentrations (127 +/- 19 vs. 59 +/- 2 densitometric units in untreated rats, p
      < 0.001). Addition of PRL to this combined treatment had no further effect.
      Treatment with T4, GH, [T4+GH] or E2 enhanced GAL labeling in the ME of
      hypophysectomized rats. The effect of estrogens was restricted to the GnRH-rich
      lateral regions of the ME. The combined treatment with [T4+GH+C+E2] restored the
      ME GAL immunoreactivity to levels observed in intact rats. In contrast, the
      increased GAL labeling observed in magnocellular neurons after hypophysectomy was
      not influenced by any hormonal treatment. In conclusion, hypophysectomy leads to
      marked reductions of hypothalamic GAL and GAL mRNA concentrations, and of GAL
      immunoreactivity in the ME. These reductions are prevented in part by a combined
      hormonal treatment associating T4, GH, C and E2, but not by any hormone given
      alone. This suggests specific pituitary hormone-dependent regulation of the
      hypophysiotropic GAL neurons. In contrast, the increased GAL labeling in
      magnocellular neurons of hypophysectomized rats persists despite hormonal
      treatment and likely represents a lesional effect on the neurohypophyseal GAL
      system.

PMID- 7529899
TI  - Cyclic 3',5'-adenosine monophosphate mediates dopamine D1-stimulated growth
      hormone release from goldfish pituitary cells.
AB  - Previously, we have demonstrated that dopamine (DA) stimulates growth hormone
      (GH) release from the goldfish pituitary through DA D1 receptors. In the present
      study, the role of cAMP in DA D1-stimulated GH release was investigated using
      static incubation of goldfish pituitary cells. The D1 agonist SKF38393 (1 nM-10
      microM) induced GH release and cAMP accumulation in a dose-dependent manner with
      ED50s of 73 +/- 32 and 109 +/- 53 nM, respectively. In contrast, the D2 agonist
      LY171555 (1 nM-10 microM) was not effective in these regards. The GH-releasing
      action of SKF38393 was mimicked by the adenylate cyclase activator forskolin (0.1
      40 microM) as well as the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine
      (0.1 microM-1 mM). Dideoxyforskolin (0.1-40 microM), a derivative of forskolin
      inactive in stimulating adenylate cyclase, did not affect basal GH secretion.
      Similar stimulatory effects on GH release were also observed using the membrane
      permeant cAMP analogs (10 microM-2 mM), dibutyryl cAMP and 8-bromo cAMP
      (8Br.cAMP). In the presence of a high dose (1 mM) of Br.cAMP, the ability of
      SKF38393 (1 nM-10 microM) to stimulate GH release was abolished, suggesting that
      the GH-releasing actions of cAMP and DA D1 stimulation are mediated through a
      common signal transduction mechanism. In the present study, the possible
      involvement of the cAMP-dependent enzyme protein kinase A (PKA) in DA D1
      stimulated GH release was also examined. The GH responses to 8Br.cAMP (1 mM) and
      SKF38393 (1 microM) were blocked by simultaneous treatment with the PKA inhibitor
      H89 (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529901
TI  - Cat-scratch encephalopathy: a cause of status epilepticus and coma in a healthy
      young adult.

PMID- 7529900
TI  - Renal cell carcinomatous meningitis: pathologic and immunohistochemical features.
AB  - We report the clinical, radiographic, pathologic, and immunohistochemical
      features of a patient with widespread meningeal carcinomatosis from renal cell
      carcinoma. Clear and spindle tumor cell subtypes infiltrated the meninges of the
      cauda equina, oculomotor nerve, spinal cord, and cerebral hemispheres, forming
      abortive glandular or tubular aggregates without evidence of parenchymal
      invasion. Cytokeratin epitopes were labeled immunohistochemically with Cam 5.2
      antibodies, but epithelial membrane antigen and neuron-specific enolase were not
      present.

PMID- 7529903
TI  - Sleep alterations and brain regional changes of serotonin and its metabolite in
      rats exposed to ozone.
AB  - Sleep alterations and brain regional changes of serotonin were studied in rats
      exposed to 1.5 ppm of ozone (O3). Results showed a significant decrease in the
      time spent in wakefulness (W) and paradoxical sleep (PS) and a significant
      increase in the time spent in slow wave sleep (SWS). Neurochemical analysis
      showed a significant increase in the metabolism of serotonin in medulla
      oblongata, pons and midbrain, while both serotonin and its metabolite were
      reduced in hypothalamus. Although other neurotransmitters could be affected by O3
      exposure, the sleep disorders observed in the present work may be related to
      alterations in the metabolism of serotonin produced by the exposure to O3.

PMID- 7529902
TI  - Changes in alpha 1-adrenergic neurotransmission alter the number of somatostatin
      receptors in the rat hippocampus.
AB  - The administration of an i.p. dose of phenylephrine (2 mg/kg) increased the
      number of [125I]Tyr11-somatostatin ([125I]Tyr11-SS) receptors and decreased their
      apparent affinity in rat hippocampal membranes 7 h after its injection. Prazosin
      (20 mg/kg, i.p.) administered 1 h before phenylephrine reversed effects of the
      latter on SS binding. Prazosin alone decreased the number of SS receptors without
      changing the affinity. The addition of phenylephrine or prazosin (10(-5) M) to
      the incubation medium did not change the SS binding characteristics. The present
      results support the notion that the alpha 1-adrenergic system regulates the
      binding of SS to its specific receptors in rat hippocampus.

PMID- 7529906
TI  - NADPH-diaphorase-positive neurons innervating the rat ovary.
AB  - Nerve cell bodies projecting to the ovary were visualized in dorsal root ganglia
      (DRG) and paravertebral ganglia after application of the retrograde tracer Fluoro
      gold to the superior ovarian and plexus nerves. The location of fluorescent cells
      in sections of ganglia was recorded and subsequently nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase histochemistry was utilized to locate
      nitric oxide synthase (NOS) whose presence indicates sites where nitric oxide
      (NO) can be synthesized. No fluorescent nerve cell bodies in paravertebral
      ganglia were NADPH-diaphorase-positive. In contrast, numerous Fluoro-gold-labeled
      nerve cell bodies in DRG at segmental levels T12-L1 were NADPH-diaphorase
      positive. Thus, many sensory neurons projecting to the ovary contain NOS and
      presumably release NO. This gaseous messenger molecule may participate in
      modulation of ovarian function.

PMID- 7529905
TI  - Immediate arousal response and adaptation to low-dose x-rays in mouse and its
      disappearance by olfactory bulbectomy and nitric oxide inhibitor.
AB  - The effects of low-dose x-rays (4 cGy) on mouse brain were examined. EEG
      recording were made on sleeping mice before, during and after exposure. Exposure
      to x-rays induced the immediate change in EEG pattern from a low-frequency and
      high-amplitude (sleep) to a high-frequency and low-amplitude (arousal). Repeated
      exposure caused a decrease in number of mice showing arousal, suggesting that
      adaptation to x-ray stimuli was acquired by mice. In the olfactory bulbectomized
      mice, no arousal response could be noticed. When mice were injected with N-nitro
      L-arginine or N-monomethyl-L-arginine, nitric oxide inhibitor, no decrease in the
      arousal mouse number occurred, even after the repeated exposure. These results
      indicate clearly that olfactory bulbs play an important role in immediate
      detection of x-rays and a possible involvement of NO in the adaptation to x-ray
      stimuli by mouse.

PMID- 7529904
TI  - Extracellular levels of serotonin in the medial pontine reticular formation in
      acute decerebrate cats with a microdialysis technique.
AB  - Extracellular levels of serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA)
      were measured in the medial pontine reticular formation of acute decerebrate
      cats. The mean basal levels of 5-HT and 5-HIAA were 26 fmol/20 microliters and 15
      pmol/20 microliters. Perfusion of the dialysis probe with high K+ and Ca(2+)-free
      Ringer solution for 60 min resulted in 4.8-8.5 x increase and 25-48% decrease in
      the extracellular levels of 5-HT, respectively, in comparison to the basal 5-HT
      levels. Perfusion with TTX-added Ringer solution for 60 min resulted in a
      consistent decrease in the extracellular levels of 5-HT.

PMID- 7529907
TI  - Confirmation of the existence of transitory corpus callosum axons in area 17 of
      neonatal cat: an anterograde tracing study using biotinylated dextran amine.
AB  - Corpus callosum (CC) axons in visual cortex were labeled anterogradely by in vivo
      biotinylated dextran amine (BDA) in neonatal cat at postnatal day (PND) 6, 10 and
      15. Labeled CC axons were distributed throughout the visual cortex including
      medial area 17. The number of CC axons in medial area 17 increased from PND 6 to
      PND 10, and then decreased from PND 10 to PND 15. At PND 15, few CC axons could
      be followed into the grey matter in medial area 17. Thus, BDA labels transitory
      CC axons that extend through all cortical layers in medial area 17, confirming
      the results revealed by in vitro DiI labeling.

PMID- 7529908
TI  - IL-1 beta-like Freund's adjuvant enhances axonal transport of opiate receptors in
      sensory neurons.
AB  - Chronic pain and inflammation increase substance P in sensory fibres of
      peripheral nerves in which opiate receptors are known to undergo axonal
      transport. The aim of the present study was to evaluate a possible modulation of
      axonal transport of opiate receptors in peripheral nerves during inflammation.
      After intraplantar injection of Freund's adjuvant to rats, the accumulation of mu
      and kappa opiate receptors increased on both sides of ligature in sciatic nerves
      of the injected paw. The contralateral side was unaffected and may serve as
      control. When IL-1 beta was injected into rat paws, the axonal transport of
      opiate receptors was increased in a similar way. This suggests that IL-1 beta
      represents a major mediator to sensitize nociceptors during inflammation through
      a process requiring retrograde signals.

PMID- 7529909
TI  - The anticonvulsant effect of the broad spectrum anticonvulsant loreclezole may be
      mediated in part by serotonin in rats: a microdialysis study.
AB  - Loreclezole is an experimental anticonvulsant drug. We found previously that
      several established anticonvulsants increase extracellular serotonin as measured
      by microdialysis. We have concluded that the increase in extracellular serotonin
      and the anticonvulsant effect produced by these anticonvulsant drugs are related
      in a cause and effect manner. To determine if anticonvulsant doses of loreclezole
      increase extracellular serotonin, we determined anticonvulsant dose-response
      relationships in genetically epilepsy-prone rats (GEPRs). Then, we administered
      ED99 doses of loreclezole to GEPRs and determined the effect on extracellular
      serotonin as measured by microdialysis in the striatum. We conclude that
      loreclezole produces a dose-related anticonvulsant effect in GEPRs and that
      anticonvulsant doses of loreclezole increase extracellular serotonin in these
      animals.

PMID- 7529910
TI  - A previously unidentified choline acetyltransferase transcript in the human
      foetal brain.
AB  - To identify choline acetyltransferase (ChAT) transcript(s) in human foetal brain
      we used the reverse polymerase chain reaction including different couples of
      oligonucleotide primers. The analysis indicated the presence of a new choline
      acetyltransferase transcript containing at its 5' end an untranslated exon (E1A)
      of 57 nucleotides in length extending from Nt 3771 to Nt 3828. It differs in the
      5'-non coding region from the M-N-R type mRNA previously described in mouse and
      rat.

PMID- 7529911
TI  - Arginine vasotocin gene expression in neuroendocrine, reproductive and
      gastrointestinal tissues of the domestic fowl: detection by reverse transcriptase
      polymerase chain reaction.
AB  - Arginine vasotocin gene transcripts in various tissues of the domestic fowl were
      detected by reverse transcriptase polymerase chain reaction followed by Southern
      blot analysis using a 209 bp fragment from the 3'-region of a cDNA encoding
      chicken arginine vasotocin as the probe. Relatively strong signals were observed
      with hypothalamic, adenohypophysial and proventricular RNA as the starting
      material. Lesser signals were obtained from RNA isolated from shell gland,
      adrenal gland, post-ovulatory follicles and ovarian thecal cells. Arginine
      vasotocin gene transcripts were undetectable in the posterior pituitary gland,
      small intestine and large intestine. These results suggest that in addition to
      its well-known antidiuretic and oxytocic actions, arginine vasotocin may act as a
      local neuromodulator or mediator and have other important autocrine or paracrine
      actions in non-hypothalamic tissues.

PMID- 7529912
TI  - cAMP is not involved in interleukin-1-induced interleukin-6 release from human
      astrocytoma cells.
AB  - We have previously shown that activation of the phosphatidyl
      inositol/phospholipase C pathway could induce interleukin 6 (IL-6) release from
      U373MG human astrocytomes cells. We also found that, although interleukin 1 beta
      (IL-1 beta) did not activate phosphatidy-linositol turnover, it induced, a robust
      release of IL-6. In the present study, we examined the role of adenylate
      cyclase/cyclic 3',5'-adenosine monophosphate (cAMP) pathway in IL-6 release.
      Agents which mimicked (dibutyryl cAMP) or stimulated (isoproterenol and
      forskolin) cAMP formation were found to induce IL-6 release and their effects
      could be potentiated by 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase
      inhibitor. On the other hand, in spite of its robust action on IL-6 release, IL-1
      beta did not stimulate cAMP formation. Other possible signal transduction
      mechanisms involved in IL-1 beta-induced IL-6 release are discussed.

PMID- 7529914
TI  - Continuous monitoring of fetal oxygen saturation by pulse oximetry.
AB  - OBJECTIVE: To compare spectrophotometric saturation values of fetal blood
      sampling to the saturation readings by pulse oximetry. METHODS: During a clinical
      trial, fetal oxygen saturation was monitored during labor by a fetal oxisensor
      and a fetal pulse oximeter. Fifty-one fetal scalp blood samples were assessed
      because of abnormal fetal heart rate (FHR) patterns. The pulse oximeter displayed
      only signal quality readings. The investigator had to perform adjustments if
      signal quality fell below 50%. After delivery, the saturation at the moment of
      fetal blood analysis could be read from a printout and compared to the saturation
      values of scalp blood sampling. RESULTS: The share of usable signal time was 51%
      overall, but only 40% in the 20-minute period during fetal blood sampling.
      Comparison with the reference method resulted in a median deviation of 6% (tenth
      percentile -10%; 90th percentile 18%) for pulse oximetry. The correlation
      coefficient between saturation values by pulse oximetry and fetal scalp blood
      sampling was 0.67. The correlation coefficient with the partial pressure of
      oxygen and oxygen saturation by pulse oximetry was 0.61, whereas it was 0.88
      between partial pressure and saturation from the spectrophotometric analysis of
      the scalp sample. CONCLUSIONS: Fetal pulse oximetry corresponds satisfactorily to
      results from fetal blood analysis. Low invasiveness and continuous monitoring are
      the advantages of this method. At present, the available sensor generates only a
      limited amount of signal time. However, in combination with FHR monitoring, pulse
      oximetry promises greatly improved detection of fetal hypoxia.

PMID- 7529913
TI  - Substance P binding sites on intestinal lymphoid aggregates and blood vessels in
      inflammatory bowel disease correspond to authentic NK-1 receptors.
AB  - Previous reports have described the ectopic expression of substance P binding
      sites on lymphoid aggregates and small blood vessels in inflammatory bowel
      disease. In this report, three non-peptide NK-1 receptor antagonists, CP-96,345,
      RP-67,580, and L-703,606 abolished saturable 125I-Bolton-Hunter substance P
      binding to the ectopically expressed receptors in frozen sections of surgically
      resected bowel from five patients with either Crohn's disease or ulcerative
      colitis. The rank order of affinity was approximately substance P approximately
      CP-96,345 approximately L-703,606 > RP-67,580. These results suggest that: (i)
      the ectopically expressed substance P binding sites in inflammatory bowel disease
      are authentic NK-1 receptors, (ii) all ectopically expressed receptors on small
      blood vessels, and lymphoid aggregates as well as normally expressed receptors on
      the bowel circular muscle have similar receptor affinities and specificities for
      substance P and the non-peptide antagonists, and (iii) non-peptide antagonists
      may be therapeutically beneficial in inflammatory bowel disease by inhibiting the
      pro-inflammatory effects of substance P acting via the NK-1 receptor.

PMID- 7529917
TI  - Catalytic activity and transformation potential of v-Src require arginine 385 in
      the substrate binding pocket.
AB  - Tyrosine kinase are important mediators of signal transduction in eukaryotic
      cells. In order to better understand the mechanism of catalysis we studied a set
      of mutants of the prototype tyrosine kinase, the c-Src protein, a homologue of
      the Rous Sarcoma virus oncogene. Based on an X-ray structure of cAMP-dependent
      protein kinase (cAPK) we mutated an arginine residue conserved in subdomain VI of
      all known kinases to a non-charged residue. This residue coordinates phosphate of
      the autophosphorylation site located in subdomain VII of cAPK and this
      interaction has been proposed to be crucial for substrate binding. The mutant
      R385A of c-Src had low kinase activity towards exogenous substrates yet was able
      to autophosphorylate at tyrosine 416. When introduced into an activated v-src
      gene the R385A mutation totally blocked cell transformation. Our data suggest
      that the function of the conserved arginine 385 is to coordinate the phosphate of
      the autophosphorylation site and to provide in this way a stable template for
      substrate binding.

PMID- 7529916
TI  - Evidence for a second cell cycle block at G2/M by p53.
AB  - Wild type p53 can induce cell cycle arrest at specific points in the cell cycle,
      in particular G1/S, an ability lost by most p53 mutants. We have previously
      reported that p53 mutant genes can rescue REF52 cells from ras-induced growth
      arrest and that over expression of wild type p53 inhibits cell growth in these
      cells. In this paper we examined whether p53 can also induce cell cycle arrest at
      the G2/M boundary of the cell cycle. To accomplish this we used the REF52 cell
      line and the temperature sensitive p53val135 mutant allele. Cells were enriched
      in the late G1 and early S phases before the temperature shift. REF52 cells
      expressing mutant-p53val135 alone with an activated H-ras gene arrest primarily
      at the G1/S and G2/M parts of the cell cycle at the restrictive temperature, as
      determined by flow cytometry analysis. These results suggest that the anti
      proliferative activity of p53 may be involved in regulation of the cell cycle at
      the G2/M restriction point as well as transit through G1/S and initiation of DNA
      synthesis.

PMID- 7529915
TI  - Substance P: endothelial localization and pharmacology in the human ovarian vein.
AB  - OBJECTIVE: To investigate the possible role of substance P as an endothelial
      factor in the local regulation of vascular tone in the human ovarian vein.
      METHODS: We performed immunolocalization of substance P in human ovarian venous
      endothelium in situ and in culture, and observed responses to substance P in
      preconstricted ring preparations of human ovarian vein in the presence of either
      the prostaglandin synthesis inhibitor indomethacin or the inhibitor of nitric
      oxide synthesis L-nitro arginine methyl ester (L-NAME), with and without luminal
      rubbing. RESULTS: Substance P was localized in a subpopulation of ovarian vein
      endothelial cells. Maximal relaxation induced by substance P was not
      significantly affected by indomethacin (10 mumol/L), but was reduced from 58.7%
      (95% confidence interval [CI] 41.3-76.1) in control experiments to 24.7% (95% CI
      18.3-31.1) after luminal rubbing and to 32.3% (95% CI 19.8-44.8) after exposure
      to L-NAME (0.1 mmol/L) (P = .001). CONCLUSION: The localization of substance P in
      ovarian vein endothelium together with vasodilator effects mediated partially via
      the endothelium suggests that the peptide has a role in the local control of
      vascular tone in this vessel.

PMID- 7529918
TI  - Evasion of p53-mediated growth control occurs by three alternative mechanisms in
      transformed thyroid epithelial cells.
AB  - Using the thyroid as a model of multistep epithelial tumorigenesis, we have used
      representative cell lines to correlate the degree of malignant transformation
      with the functional status of p53 and the integrity of cell-cycle check-points.
      Three distinct phenotypes were observed: Type I lines, derived from poorly
      differentiated human thyroid cancers, expressed high levels of mutant p53
      protein; Type II, also poorly-differentiated but derived from rat, showed over
      expression of wild-type (wt) p53 with marked cell-cell heterogeneity: Type III,
      from well-differentiated human cancers, contained uniformly low levels of wt p53.
      All cell lines containing wt p53 retained a near-normal induction of p53 by DNA
      damage. However, the ability to undergo growth arrest differed strikingly.
      Whereas Type I and II lines had lost both G2/M and G1/S check points, Type III
      cells retained both. In Type III cells, as in diploid human fibroblasts, mutant
      p53 expression specifically abrogated G1/S check-point function with no other
      change in phenotype. These data demonstrate 3 mechanisms for evasion of p53
      growth control: (i) direct mutation (ii) indirect inactivation, or (iii)
      'avoidance' of activation, most probably due to failure to reach a critical
      threshold of DNA damage.

PMID- 7529920
TI  - How receptors work: mechanisms of signal transduction.

PMID- 7529921
TI  - [Influence of the granulocyte growth factor on the cost of bone marrow autografts
      in oncologic hematology].
AB  - OBJECTIVE: It is now possible to achieve prolonged remission of malignant
      lymphoma and certain cancers with high-dose chemotherapy followed by autograft
      with haematopoietic stem cells. We tested such a protocol, evaluating
      haematologic recovery, in order to determine the total cost of hospitalization.
      METHODS: Sixteen patients were included in the study, 7 had severe or relapsing
      lymphoma, 7 had breast cancer or cancer of the ovary and 2 had cancer of the
      testicule. Mean age was 34 years, 14 patients reached complete remission and
      relapse occurred in 2. Ten patients were given granulocyte growth factor and 6
      were given a placebo. RESULTS: The duration of aplasia (number of days with a
      white cell count below 1 x 10(9)1) ranged from 10 to 32 days. In patients treated
      with granulocyte growth factor, it was shorter (16 vs 22 days) as was
      hospitalization time (27 vs 33 days). The cost of the autograft ranged from
      100,000 FF to 250,000 FF and the average cost for the 16 patients was 149,500 FF
      including: 83,600 FF (56.4%) for hospitalization itself, 33,200 FF (22%) for
      drugs, mostly antibiotics, and 19,000 FF (13%) for laboratory examinations and
      14,000 FF (9%) for blood transfusions. Total cost was lower in patients given
      granulocyte growth factor, 142,000 FF vs 166,000 FF for those given placebo.
      CONCLUSION: In order to shorten the duration of the aplasia period,
      haematopoietic growth factors are widely used in autograft protocols. Our
      findings give an evaluation of the cost in 16 patients and show that cost
      decreases in patients given granulocyte growth factor. This reduction is cost is
      related to a lower hospitalization cost and not a reduction in the number of
      drugs and transfusions required.

PMID- 7529919
TI  - Keratin gene mutations in human skin disease.

PMID- 7529922
TI  - Predicting molecular interactions and inducible complementarity: fragment docking
      of Fab-peptide complexes.
AB  - Antibody-antigen interactions are representative of a broad class of receptor
      ligand interactions involving both specificity and potential inducible
      complementarity. To test possible mechanisms of antigen-antibody recognition and
      specificity computationally, we have used a Metropolis Monte Carlo algorithm to
      dock fragments of the epitope Glu-Val-Val-Pro-His-Lys-Lys to the X-ray structures
      of both the free and the complexed Fab of the antibody B13I2 (raised against the
      C-helix of myohemerythrin). The fragments Pro-His and Val-Pro-His, which contain
      residues experimentally identified as important for binding, docked correctly to
      both structures, but all tetrapeptide and larger fragments docked correctly only
      to the complexed Fab, even when torsional flexibility was added to the ligand.
      However, only tetrapeptide and larger fragments showed significantly more
      favorable energies when docked to the complexed Fab coordinates than when docked
      to either the free Fab or a non-specific site remote from the combining site.
      Comparison of the free and complexed B13I2 structures revealed that atoms within
      5 A of Val-Pro-His showed little movement upon peptide binding, but atoms within
      5 A of the other four epitope residues showed greater movements. These results
      computationally distinguished recognition and binding processes with practical
      implications for drug design strategies. Overall, this new fragment docking
      approach establishes distinct roles for the "lock-and-key" (recognition) and the
      "handshake" (binding) paradigms in antibody-antigen interaction, suggests an
      incremental approach to incorporating flexibility in computational docking, and
      identifies critical regions within receptor binding sites for ligand recognition.

PMID- 7529924
TI  - Topical treatment of venous leg ulcers with a prostacyclin hydrogel: a double
      blind trial.
AB  - In a randomized, double-blind, placebo controlled study in patients with venous
      leg ulcers, the efficacy and tolerability of topical applications of a
      prostacylin hydrogel (iloprost) was investigated. 34 patients were allocated to
      the placebo treatment and 65 patients were allocated to the iloprost treatment.
      The iloprost treatment commenced with 10 micrograms/ml for the first 3 days and
      was increased to 40 micrograms/ml for the remaining treatment period if well
      tolerated. Maximally 3 ml of the hydrogel were applied daily on the ulcer base
      for a period of 8 weeks. The total area of the ulcers at the last individual
      assessment was chosen as the main criterion for evaluation of efficacy. Both
      concentrations of iloprost were well tolerated with almost the entire trial
      population on iloprost being treated with the 40 micrograms/ml iloprost hydrogel.
      With regards to efficacy, no significant difference was found in favour of the
      iloprost treatment.

PMID- 7529923
TI  - Effects of endogenously produced arachidonic acid metabolites on rat mesangial
      cell proliferation.
AB  - The role of endogenously produced arachidonic acid metabolites on
      glomerulonephritis was investigated using cultured rat mesangial cells. The
      cultured mesangial cells could produce prostaglandin (PG) E2 and F2 alpha and 12
      hydroxyeicosatetraenoic acid (12-HETE). The treatment of the mesangial cells with
      indomethacin enhanced the cell growth stimulated by 10% fetal calf serum (FCS).
      This stimulatory effect was significantly attenuated by concomitant treatment
      with PGE2, but not with PGF2 alpha. To test whether the mechanism by which PGE2
      inhibited the mesangial cell growth is related to in the increment of cyclic AMP
      (cAMP), we examined the effect of dibutyryl cAMP on mesangial cell growth. As
      expected, treatment with dibutyryl cAMP decreased the cell proliferation.
      Moreover treatment with KT-5720, a protein kinase A (PKA) inhibitor, stimulated
      the cell growth as well as indomethacin. These data strongly suggest that the
      inhibition of mesangial cell growth by PGE2 involves an activation of PKA. In
      contrast, treatment with baicalein, a specific inhibitor of 12-lipoxygenase,
      inhibited the mesangial cell growth. The up and down regulations by arachidonic
      acid metabolites were also observed in the growth induced by platelet-derived
      growth factor (PDGF). These results suggest that endogenously produced
      arachidonic acid metabolites are involved in the regulation of mesangial cell
      growth.

PMID- 7529927
TI  - The anatomic basis for arteriovenous shunting in human lower leg fascial flaps.
AB  - Clinical experience has suggested that arteriovenous shunting may occur in
      fascial flaps. The anatomic basis for this has not been fully established. The
      aim of this study was to determine the size, location, and nature of
      arteriovenous shunts in human lower leg deep fascia. Deep fascia was harvested
      from the limbs of nine embalmed cadavers. Small pieces of fascial tissue were
      studied with the aid of three staining techniques (methylene blue, oil red-O
      triethyl phosphate, and Gomori's rapid one-stage trichrome technique), which were
      used to enable the microvascular anatomy to be visualized more clearly.
      Arteriovenous anastomoses proximal to the capillary bed and with an external
      diameter greater than 50 microns were identified in the suprafascial, subfascial,
      and intrafascial plexuses but were not found to be a common feature of the
      microvascular anatomy. Thoroughfare channels within the capillary bed and with an
      external diameter ranging from 12 to 25 microns were frequently identified in all
      three levels of the fascial plexus. The results of this study establish an
      anatomic basis for arteriovenous shunting in fascial flaps.

PMID- 7529925
TI  - Serotonergic control of androgen-induced dominance.
AB  - The present study investigates the role of serotonergic systems in anabolic
      steroid-induced aggression. An animal model of aggressive dominance was used to
      assess the chronic effects of testosterone propionate. When rats that had become
      dominant following administration of testosterone propionate received
      serotonergic agonists with selectivity for the 5-HT1A receptor (8-OH-DPAT,
      buspirone, gepirone), the 5-H1B receptor (eltoprazine, TFMPP), or the 5-HT2A/2C
      receptor (DOM), a dose-dependent decrease in dominance was demonstrated.
      Pretreatment with three serotonergic antagonists (pizotyline, pirenpirone, and
      pindolol) blocked agonist-induced reductions in dominance in varying degrees.
      Nonserotonergic agonists with CNS depressant effects were also tested in dominant
      animals. The benzodiazepine, chlordiazepoxide, did not reduce dominance except at
      doses that interfered with motor behavior. The opioid agonist, morphine, dose
      dependently decreased dominance, but this effect was reversible with
      administration of the serotonergic antagonist, pirenpirone, suggesting the
      antidominant effect of morphine had a serotonergic component. Biochemical
      experiments demonstrated that following chronic testosterone propionate, there
      was a decrease in levels of 5-HT and 5-HIAA in the hippocampus but not in the
      striatum or the frontal cortex. Chronic testosterone propionate also caused an
      increase in the affinity of [3H]8-OH-DPAT for the 5-HT1A receptor but no
      corresponding change in the density of 5-HT1A binding sites in the hippocampus.
      There was also no change in the properties of the 5-HT2 receptor in the frontal
      cortex following chronic testosterone propionate. These data suggest that
      serotonergic systems may play an important role in the control of anabolic
      steroid-induced aggressive dominance.

PMID- 7529926
TI  - Effect of tachykinins on the need-free sodium intake of female rats: a continuous
      intracerebroventricular infusion study.
AB  - The present study investigated the effect of 24-h continuous ICV infusion of four
      different tachykinins on the enhanced need-free sodium intake induced by previous
      repeated sodium depletions in female rats. Female rats were employed because, in
      response to sodium depletions, they develop a higher need-free sodium intake than
      male rats. The following tachykinins were used: eledoisin, substance P (SP),
      [Sar9,Met(O2)11]SP and [Asp5,6,MePhe8]SP(5-11), also referred to as NH2-senktide,
      all at the same doses of 300 or 600 ng/h x 24 h. Food pellets, water, and 3% NaCl
      sodium solution were freely available. Eledoisin and NH2-senktide were more
      potent than SP in reducing the need-free sodium intake. On the other hand,
      [Sar9,Met(O2)11]SP had no effect. None of the tachykinins employed completely
      blocked the intake. Water intake was reduced, but this reduction was apparently a
      consequence of reduced intake of hypertonic sodium chloride solution, because at
      the same doses TKs did not inhibit water intake in a single-bottle test. Food
      intake remained unchanged at either dose used. These findings confirm previous
      studies in which pulse injection of the same drugs potently inhibited sodium
      intake. They also demonstrate that tachykinins endowed with high affinity for the
      NK3 receptor are the most potent in inhibiting sodium intake. Furthermore, these
      findings indicate that the tachykinins reduce the need-free sodium intake only
      during the infusion period, indicating that in these conditions they do not evoke
      either aversion for salt, or toxic consequences in the follow-up period.

PMID- 7529929
TI  - Cation transport mediated by Na+,K(+)-adenosine triphosphatase in lymphoblastoma
      cells from patients with bipolar I disorder, their relatives, and unrelated
      control subjects.
AB  - In an investigation of cation transport in bipolar affective disorder, we have
      measured parameters related to Na+,K(+)-adenosine triphosphatase, the enzyme that
      carries out active transport of sodium and potassium, in lymphoblastoid cells
      cultured from patients with bipolar affective disorder, age-matched nonaffected
      family relatives, and unrelated control subjects. Patients had lower ion
      transport per cell and per transport enzyme site than did related or unrelated
      control subjects. The rate of transport per cell appeared higher in nonaffected
      relatives of patients than in unrelated control subjects, though this difference
      did not reach significance. These data suggest that abnormally regulated ion
      transport may be associated with bipolar affective disorder independently of
      clinical state.

PMID- 7529930
TI  - The European-American exchange.
AB  - The European-American exchange of infectious diseases was responsible for the
      demographic havoc of the native population in the New World after 1492. Prior to
      this date medical writers describe the presence in Spain of viral diseases like
      influenza, parotitis, smallpox, measles, poliomyelitis, and rabies; there were
      also rickettsiasis, diphtheria, salmonellosis, plague, tubercolosis, leprosy,
      malaria, scabies and tinea. In America, before European arrivals, there were no
      records of human viral diseases, though there were records of rickettsiasis,
      treponematosis--pinta, yaws and syphilis--leihsmaniasis, amibiasis and perhaps
      leprosy. With the discovery of America in 1492, Columbus's sailors were
      contaminated by yaws and spread this disease into Europe. In 1493 influenza, as a
      zoonosis, was introduced into Santo Domingo and was responsible for the
      annihilation of the natives of the Antilles in less than a quarter of a century;
      in 1518 smallpox was also introduced in Santo Domingo and then to the American
      continent by negro slaves: by the same means measles were introduced in 1531. The
      previous existence or introduction of other infectious diseases in America is
      also discussed.

PMID- 7529931
TI  - Disease exchange across the tropical Atlantic.
AB  - The fifteenth-century encounter between previously separate disease environments
      was not simply an encounter between Europe and the Americas. It was preceded by
      an encounter between Europe and tropical Africa and followed by a still-more
      intense transmission of diseases across the tropical Atlantic, mainly from Africa
      to the Americas. This transmission principally involved smallpox, yaws, yellow
      fever, and falciparum malaria. Many other vector-borne diseases failed to make
      the transfer for lack of suitable vectors in the Americas. The African diseases
      contributed even more than those from Europe to the depopulation of the humid
      tropics in the Americas. They also set up conditions that made residence in the
      tropical Americas dangerous for newly arrived people from Europe.

PMID- 7529928
TI  - Cyclic AMP stimulates K+ channel activity in mesophyll cells of Vicia faba L.
AB  - Whole-cell patch-clamp recordings from Vicia faba mesophyll protoplasts reveal
      that outward K+ current is increased in a dose-dependent fashion by intracellular
      application of cAMP. The enhancement of the outward current by cAMP is specific
      and it cannot be mimicked by a series of nucleotides that includes AMP, cGMP, and
      GMP. The enhancement is evoked by micromolar concentrations of cAMP in the
      presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine. PKI or
      Walsh inhibitor, a specific peptide inhibitor of cAMP-dependent protein kinase
      (PKA), inhibits the outward K+ current. Adenosine 3',5'-phosphothioate, a
      competitive inhibitor of PKA, has a similar effect. Conversely, the catalytic
      subunit of PKA (cAMP independent) from bovine brain enhances the magnitude of the
      outward K+ current in the absence of added cAMP. Our results indicate that cAMP
      modulates K+ channel activity in mesophyll cells and suggest that this modulation
      occurs through a cAMP-regulated protein kinase.

PMID- 7529932
TI  - Smallpox: emergence, global spread, and eradication.
AB  - Speculatively, it is suggested that variola virus, the cause of smallpox, evolved
      from an orthopoxvirus of animals of the central African rain forests (possibly
      now represented by Tatera poxvirus), some thousands of years ago, and first
      became established as a virus specific for human beings in the dense populations
      of the Nile valley perhaps five thousand years ago. By the end of the first
      millennium of the Christian era, it had spread to all the densely populated parts
      of the Eurasian continent and along the Mediterranean fringe of north Africa. It
      became established in Europe during the times of the Crusades. The great voyages
      of European colonization carried smallpox to the Americas and to Africa south of
      the Sahara. Transported across the Atlantic by Europeans and their African
      slaves, it played a major role in the conquest of Mexico and Peru and the
      European settlement of north America. Variolation, an effective preventive
      inoculation, was devised as early as the tenth century. In 1798 this practice was
      supplanted by Jenner's cowpox vaccine. In 1967, when the disease was still
      endemic in 31 countries and caused ten to fifteen million cases and about two
      million deaths annually, the World Health Organization embarked on a programme
      that was to see the disease eradicated globally just over ten years later, and
      the world was formally declared to be free of smallpox in May 1980. Smallpox is
      unique--a specifically human disease that emerged from some animal reservoir,
      spread to become a worldwide, severe and almost universal affliction, and finally
      underwent the reverse process to emergence, namely global eradication.

PMID- 7529933
TI  - Percutaneous sclerotherapy of lymphangiomas.
AB  - PURPOSE: The authors report their experience with percutaneous image-guided
      sclerotherapy for treatment of unresectable lymphangiomas. MATERIALS AND METHODS:
      Five patients with unresectable lymphangiomas of the pelvis (n = 2), neck (n =
      1), abdomen (n = 1), or leg (n = 1) were treated at two medical centers with
      sclerotherapy, with use of doxycycline as the sclerosant. Computed tomography was
      used to guide the procedures, with supplemental lymphoscintigraphy, ultrasound,
      and magnetic resonance imaging used as needed. RESULTS: Symptomatic relief of
      lymphedema, lymphorrhea, or a decrease in size of lymphatic pools was achieved,
      to varying degrees, in the five patients. Follow-up is ongoing, and further
      sclerotherapy may be indicated as the clinical course dictates. CONCLUSION:
      Percutaneous sclerotherapy with doxycycline is safe and appears effective for
      palliative treatment of unresectable lymphangiomas on the basis of our initial
      clinical experience.

PMID- 7529934
TI  - Metabolic alterations in the neonate and infant brain during development:
      evaluation with proton MR spectroscopy.
AB  - PURPOSE: To evaluate the usefulness of hydrogen-1 magnetic resonance (MR)
      spectroscopy in the evaluation of the developing brain. MATERIALS AND METHODS:
      Localized MR spectra were obtained with an echo time of 272 msec from the brain
      of 78 neonates and infants aged 1 week to 100 months. All patients were
      retrospectively classified into three groups on the basis of neurologic
      development: abnormal (group 2, n = 21), normal despite minor neurologic signs
      (group 1, n = 23), and normal (group 0, n = 34). RESULTS: Seventeen patients in
      group 2 and eight patients in group 1 revealed abnormally low N-acetylaspartate
      (NAA)/choline or NAA/creatine ratios compared with those obtained in group 0. MR
      spectroscopy was slightly more useful in the differentiation of patients in
      groups 2 and 1 (chi 2 test, P < .005) than MR imaging (P < .01). CONCLUSION: H-1
      MR spectroscopy provides prognostic information about the brain in healthy and
      neurologically damaged infants and augments the value of MR imaging.

PMID- 7529936
TI  - Carcinoma of the prostate: race as a prognostic indicator in definitive radiation
      therapy.
AB  - PURPOSE: To characterize the racial differences in prognostic factors and
      treatment outcome for patients undergoing radiation therapy for carcinoma of the
      prostate. MATERIALS AND METHODS: From January 1975 through December 1989, 489
      white and 157 black men with carcinoma of the prostate underwent irradiation.
      Factors analyzed were patient age, tumor stage and grade, prostate-specific
      antigen (PSA) levels, and disease-control and survival rates. RESULTS: More black
      patients than white patients were found to have poorly differentiated tumors.
      Black patients had higher PSA levels before and after treatment, resulting in a
      higher distant failure rate and poorer overall, cause-specific, and disease-free
      survival rates. CONCLUSION: Black men have more aggressive prostatic tumors, a
      higher rate of metastasis, and a poorer survival rate than do white men.

PMID- 7529938
TI  - Juvenile chronic arthritis in India: is it different from that seen in Western
      countries?
AB  - Medical records of 89 children with juvenile chronic arthritis attending the
      clinical immunology outpatient department of a tertiary care hospital were
      analysed. Polyarticular type of juvenile chronic arthritis was the most common,
      followed by pauciarticular and systemic onset types. No patient with the early
      onset pauciarticular disease subset, which is associated with iridocyclitis and
      antinuclear antibody (ANA) positivity was seen. Uveitis was observed in only one
      patient with late onset pauciarticular disease. The ANA positivity rate (1/89)
      was very low. Polyarticular onset type disease had a higher incidence of
      deformities.

PMID- 7529937
TI  - Prostate cancer: US-guided percutaneous cryoablation. Work in progress.
AB  - PURPOSE: To present early results of cryosurgical ablation of prostate cancer
      with an ultrasound-guided percutaneous technique. MATERIALS AND METHODS:
      Cryosurgery was performed in 210 patients; near complete 3- and 6-month follow-up
      data were available for 130. Androgen ablation therapy was used to decrease the
      size of the prostate gland for optimal freezing. Prostate-specific antigen (PSA)
      and prostatic biopsy studies were performed at 3, 6, and 12 months. RESULTS:
      Gland volume decreased from 29 cm3 +/- 14.1 to 20.4 cm3 +/- 8.4 (P < .0001) after
      androgen ablation. Rates of positive biopsy findings at 3, 6, and 12 months were
      7.7%, 3.3%, and 2.3%, respectively. Serious complications were minimal and
      included no deaths, urethrorectal fistulas in five patients, and total
      incontinence in three. Mean PSA levels decreased from 12.6 +/- 16.1
      preoperatively to 0.35 +/- 0.75 at 3 months, 0.54 +/- 1.1 at 6 months, and 0.43
      +/- 0.78 at 12 months (persistent cancers excluded). CONCLUSION: These
      preliminary results demonstrate that cryosurgery can cause necrosis of prostate
      cancer. Long-term results and randomized trials are necessary to determine if
      this means longer disease-free intervals and increased patient survival compared
      with results of current therapeutic methods.

PMID- 7529935
TI  - Musculoskeletal neoplasms: preoperative evaluation with MR angiography.
AB  - PURPOSE: To assess the ability of magnetic resonance (MR) angiography to depict
      vascularity of musculoskeletal neoplasms. MATERIALS AND METHODS: Two-dimensional
      (2D) time-of-flight (TOF) MR angiography was compared with conventional
      arteriography during staging of musculoskeletal tumors in 23 prospective
      examinations. Phase-contrast (PC) MR angiography was also performed in 19 cases
      and evaluated as a possible supplement to 2D TOF imaging. RESULTS: Of named
      vessels, 92% in proximity to tumor were noted by blinded readers. The PC
      technique provided supplemental data in 47% of cases, usually related to better
      delineation of in-plane feeder vessels and areas with pulsatile blood flow. Of
      the 28 branch feeder vessels, 23 were noted on both conventional arteriograms and
      MR angiograms in a nonblinded review, but 16 were difficult to distinguish as
      feeders because of lack of associated tumor blush. CONCLUSION: MR angiography has
      promise to replace conventional arteriography for orthopedic preoperative
      planning.

PMID- 7529939
TI  - Accessory signalling by B7-1 for T cell activation induced by anti-CD2: evidence
      for IL-2-independent CTL generation and CsA-resistant cytokine production.
AB  - Resting T cells can be activated by selected pairs of anti-CD2 MoAb. Activation
      is dependent on the presence of accessory cells, which can be replaced by either
      anti-CD28, or by the combination of IL-1 beta and IL-6. The present study was
      undertaken to investigate accessory signalling by B7-1, the natural ligand of
      CD28, in this pathway of T cell activation. 3T6 mouse fibroblasts were
      transfected with human B7-1 and used as accessory cells in cultures of purified
      resting human T cells. In the presence of a stimulating pair of anti-CD2 MoAb, T
      cell proliferation, production of cytokines (IL-2, IL-4, IL-10, GM-CSF, IFN-gamma
      and TNF-alpha), and generation of cytotoxic T lymphocytes were all supported by
      B7-1(+) 3T6 cells but not by control 3T6 cells. Blocking studies with anti-IL-2 +
      anti-IL-2R MoAb revealed both IL-2-dependent and IL-2-independent CTL generation
      after B7-1-mediated costimulation. Moreover, a partial or complete resistance to
      inhibition with CsA was observed for IL-2 production and CTL generation
      respectively in the presence of the costimulatory signal derived from B7-1-CD28
      interaction. Anti-CD2 MoAb with B7-1 costimulation could directly induce
      proliferation, IL-2 production and generation of CTL activity in highly purified
      CD8+ T cells without the help of CD4+ T cells. We conclude that CD28 ligation
      with the natural ligand B7-1 provides a strong accessory signal for CD4 and CD8
      cell activation through CD2.

PMID- 7529940
TI  - A hot spot of binding energy in a hormone-receptor interface.
AB  - The x-ray crystal structure of the complex between human growth hormone (hGH) and
      the extracellular domian of its first bound receptor (hGHbp) shows that about 30
      side chains from each protein make contact. Individual replacement of contact
      residues in the hGHbp with alanine showed that a central hydrophobic region,
      dominated by two tryptophan residues, accounts for more than three-quarters of
      the binding free energy. This "functional epitope" is surrounded by less
      important contact residues that are generally hydrophilic and partially hydrated,
      so that the interface resembles a cross section through a globular protein. The
      functionally important residues on the hGHbp directly contact those on hGH. Thus,
      only a small and complementary set of contact residues maintains binding
      affinity, a property that may be general to protein-protein interfaces.

PMID- 7529942
TI  - Defects in the barrier.

PMID- 7529941
TI  - Protection against cholera.

PMID- 7529943
TI  - Effects of tunicamycin on the pH-activity pattern of acid phosphatase in
      Pseudomonas pseudomallei.
AB  - The liquid culture of Pseudomonas pseudomallei shows a complex feature in in the
      pH-activity pattern of acid phosphatase, not a single peak curve. There was an
      evident tendency that the higher activity shifted to the higher pH range with the
      growth of culture. The culture in the presence of tunicamycin (20 micrograms/ml)
      showed a decreased activity selectively in the higher pH range, while the
      activity in the lower pH was more heat-labile. The bacterial cells grown on agar
      plates containing tunicamycin were more heat-labile than the untreated control
      cells. The glucosidase-treatment reduced the enzymatic activity (of the
      phosphatase-active fractions from the living cells) with the shift of the optimum
      pH to lower pH. These observations together with some collateral findings suggest
      that the pH-activity pattern of acid phosphatase in P. pseudomallei is associated
      with the development of precursor enzyme proteins to mature glycoproteins.

PMID- 7529946
TI  - Angiogenesis and the blood-brain barrier in intracerebral solid and cell
      suspension grafts.
AB  - Solid and suspension grafts of fetal central nervous system (CNS) tissue rapidly
      reform an intact blood-brain barrier (BBB), whereas solid grafts of peripheral
      nervous system (PNS) tissue fail to establish a BBB as detected by horseradish
      peroxide (HRP) leakage, administrated intravenously. We examined the acute
      changes in the BBB after grafting of fetal CNS tissue in solid and suspension
      form and superior cervical ganglion (SCG) and PNS tissue in the same manner.
      Adult rats (n = 20) received fetal (day 14-15) forebrain grafts (either solid or
      cell suspension) to their rostral corpus callosum bilaterally. A second group (n
      = 20) received SCG solid and cell suspension grafts at the same coordinates with
      the same technique. The animals were killed on first, third, seventh, and tenth
      days after grafting. Intravenous HRP (Sigma, type VI, 75 mg/5-g rat) was given 1
      hour before perfusion with mixed aldehydes. Fifty-micron coronal sections were
      examined for the presence and location of the graft by cresyl violet and AChE
      staining and Mesulam's TMB method to detect HRP leakage. HRP leakage was detected
      in the parenchyma in all groups on the first and the third days post
      transplantation indicating a disrupted BBB. No HRP reaction was seen at days 7
      and 10 in groups receiving fetal forebrain tissue whether solid or cell
      suspension. Solid grafts of SCG consistently demonstrated HRP leakage from the
      first through the tenth day. However, cell suspension of SCG established a BBB by
      7 days. These results suggest that within the solid grafts of CNS and PNS tissue,
      the permeability of the vessels is dictated by the transplanted tissue itself.
      When cell suspensions of the same tissue are introduced, host CNS tissue
      dominates as the local environment resulting in non-leaky vasculature within the
      graft.

PMID- 7529947
TI  - Indocyanine green/ICG/staining and demarcation of tumor margins in a rat glioma
      model.

PMID- 7529945
TI  - A clinicpathological study of hepatocellular carcinoma in Nagasaki, south-western
      Japan: the association of hepatitis B and C viruses.
AB  - Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in Japan as
      well as Southeast Asia and Africa. On 89 patients with HCC in the Nagasaki City
      area were performed serological examinations and histopathological studies. The
      number of HBsAg positive and anti-HCV positive was three (3%), HBsAg positive and
      anti-HCV negative 21 (24%), HBsAg negative and anti-HCV positive 58 (65%) and
      HBsAg negative and anti-HCV negative seven (8%). These results strongly suggest
      that HCV infection is a more important factor in the development of HCC than HBV
      infection. The HBsAg negative and anti-HCV positive group showed a higher mean
      age and a higher male to female ratio than the HBsAg positive and anti-HCV
      negative group. Histological examinations showed no differences between these two
      groups. In addition, all cases were complicated with chronic hepatitis (CH) or
      liver cirrhosis (LC) in adjacent liver tissue. These findings suggest that CH and
      LC seem to play an important role in the pathogenesis of HCC.

PMID- 7529948
TI  - Immunohistochemical evidence for GABA and glycine-containing trigeminal
      premotoneurons in the guinea pig.
AB  - Electrophysiological studies have suggested that inhibition of trigeminal
      motoneurons during mastication and the jaw-opening reflex are mediated by last
      order interneurons (premotoneurons) utilizing GABA and glycine [Chandler et al.
      (1985), Brain Res., 325:181-186; Enomoto et al. (1987), Neurosci. Res., 4:396
      412; Goldberg and Nakamura (1968), Experientia, 24:371-373; Kidokoro et al.
      (1968), J. Neurophysiol., 31:695-708; Nakamura et al. (1978), Exp. Neurol., 61:1
      14]. In the present study we performed a series of double-labeling experiments in
      guinea pigs to determine the location of neurons which contain GABA (gamma
      aminobutyric acid) or glycine that project to the trigeminal motor nucleus (Mo5).
      This was accomplished by performing immunohistochemical staining in combination
      with a retrograde tract tracing technique using colloidal gold bound to
      inactivated WGA-HRP (wheat germ agglutin-horseradish peroxidase) (gWGA-HRP) as
      our retrograde tracer. Neurons which had a positive immunoreactivity to GABA or
      GAD (glutamic acid decarboxylase) and contained the retrograde marker were
      located in regions adjacent to the Mo5 such as the intertrigeminal,
      supratrigeminal, peritrigeminal and rostral portions of the parvocellular
      reticular formation alpha. Neurons which had a positive immunoreactivity to
      glycine and contained the retrograde marker were identified in the parvocellular
      reticular formation, the spinal trigeminal nucleus oralis, supratrigeminal and
      intertrigeminal regions. These data provide anatomical evidence for GABAergic and
      glycinergic projections to Mo5.

PMID- 7529949
TI  - Celite and kaolin produce differing activated clotting times during
      cardiopulmonary bypass under aprotinin therapy.
AB  - Since the introduction of the proteinase inhibitor aprotinin in cardiac surgery,
      a strong increase of the activated clotting time (ACT) during the extracorporeal
      circulation phase (ECC) was reported in many clinical studies, but with a lack of
      correlation between ACT and heparin concentration. In searching for a cause of
      this inconsistency we investigated different surface activators of the ACT in a
      clinical study. During ECC ACT was measured in parallel, using a Hemochron device
      and corresponding tubes (nominally 12 mg celite activator) for celite ACT, and a
      HemoTec device with corresponding double tubes (nominally 0.1 ml kaolin
      activator) for kaolin ACT. Under the conditions of ECC, the kaolin ACT values
      (482 +/- 145 sec) were significantly lower than the celite ACT values (985 +/-
      267 sec). These results were confirmed in ex-vivo experiments using an activated
      partial thromboplastin time (aPTT) model. With heparin alone, aPTT activated with
      celite and kaolin were similar. Including aprotinin in this model, the celite
      aPTT showed no correlation to the heparin concentration, whereas the kaolin aPTT
      remained well correlated to the heparin concentration and similar to the values
      without aprotinin. With aprotinin alone there were no changes of the aPTT times,
      whereas the celite ACT times were without any correlation. Our results indicate
      that using kaolin instead of celite the ACT measurements under aprotinin therapy
      stay in the same ranges as without application of aprotinin: aprotinin has no
      detectable influence on kaolin-activated ACT. In our opinion, kaolin should be
      used as the surface activator for ACT measurements under the conditions of ECC,
      heparinization, and aprotinin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7529944
TI  - A longitudinal study of seroreactivities to a major blood stage antigen
      (Pf155/RESA) of the malaria parasite Plasmodium falciparum in an endemic area of
      Thailand.
AB  - We have performed a longitudinal study of the formation of antibodies to
      Plasmodium falciparum in an area of Thailand where malaria transmission is
      moderate and seasonal. The study population comprised 118 subjects living in two
      villages 230 km southeast of Bangkok. All subjects included in this study were
      seropositive for antibodies to the blood stages of P. falciparum but only
      approximately 80% had antibodies to the blood stage antigen Pf155/RESA when
      assayed by erythrocyte membrane immunofluorescence (EMIF) or peptide ELISA during
      the period of maximal transmission. The reduced capacity to form these antibodies
      in a significant fraction of subjects living under comparable environmental and
      socio-economic conditions may reflect a genetic but antigen specific non
      responsiveness. Both seropositivity and mean antibody titers to Pf155/RESA and
      its B-cell epitopes tended to be slightly higher during the rainy than during the
      dry season but the seasonal variations were slight and statistically not
      significant. Parasite rates were significantly higher in the rainy than in the
      dry season in both the EMIF positive and the EMIF negative groups. However,
      during the rainy season, the parasite rates in subjects with no or low titered
      antibodies to Pf155/RESA were significantly higher than those in subjects having
      such antibodies. The results suggest that antibodies to Pf155/RESA and some of
      its defined epitopes may be of importance for controlling parasitemias.

PMID- 7529950
TI  - Changes of serum hepatitis C virus levels in patients with chronic hepatitis C
      treated with two courses of interferon administration.
AB  - To assess the efficacy of repeated interferon (IFN) administration in patients
      with chronic hepatitis C unresponsive to initial therapy, serum hepatitis C virus
      (HCV)-RNA levels were measured in 12 patients who had failed prior IFN therapy.
      Serum HCV-RNA was assayed by measuring DNA complementary to HCV-RNA using a
      quantitative reverse transcription-polymerase chain reaction assay. The mean
      total dose of IFN was 227.8 mega-units for first treatment and 270.7 mega-units
      for second treatment. Five responders with a normal alanine aminotransferase
      (ALT) concentration (less than 40 IU/liter) at the end of the first treatment
      also had a normal ALT concentration at the end of the second treatment. By
      contrast, all nonresponders with an elevated ALT concentration during the first
      treatment likewise had an elevated ALT concentration at the end of the second
      treatment. HCV-RNA levels before the first treatment varied from 10(6) to 10(8)
      copies/microliters. The serum HCV-RNA levels fell in 9 out of 10 patients after
      the first treatment and in 11 out of 12 patients after the second treatment. One
      patient had unchanged normal serum ALT levels after two courses of IFN treatment.
      These results suggested that the outcome of a second course of IFN treatment was
      similar biochemically and virologically to a first course, and that patients who
      did not respond initially seldom respond to additional IFN therapy. Therefore,
      readministration of IFN should be restricted to patients who respond
      biochemically and virologically to initial treatment. The optimal second dose
      shall be determined with further studies.

PMID- 7529952
TI  - Influence of hexachlorocyclohexane on phosphoinositides in rat erythrocyte
      membranes and brain.
AB  - Single exposure of rats to hexachlorocyclohexane (100 mg/kg) did not cause any
      significant change in phosphoinositide levels in rat erythrocyte membrane and
      cerebrum (fore brain) 2 or 24 h after exposure. However, the phosphoinositide
      turnover and generation of second messengers from phosphoinositides were
      increased in the treated erythrocyte membranes as judged from a marked increase
      in the incorporation of [2-3H]inositol into phosphoinositides 24 h after the
      treatment. A significant decrease in phosphatidylinositol (PI),
      phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate
      (PIP2) was observed in the erythrocyte membrane and cerebrum of rats repeatedly
      exposed to the pesticide for 3 or 6 months. This drastic reduction in
      phosphoinositide levels suggests adverse effects on vital membrane and cell
      functions modulated by phosphoinositides.

PMID- 7529953
TI  - Inhibitory effect of lead on the proliferation of cultured vascular endothelial
      cells.
AB  - We investigated the effect of lead nitrate (0.5, 1.0, 2.0 or 5.0 microM) on the
      proliferation of cultured bovine aortic endothelial cells. After exposure to
      lead, the number of cells and the incorporation of [3H]thymidine into the acid
      insoluble fraction of the cells were reduced in parallel in a concentration
      dependent manner. Histologically, lead treatment resulted in a decrease in the
      cell number accompanied by a change in the cell shape from polygonal to spindle;
      however, no degenerative change was observed except in 5.0 microM lead-treated
      cells. Furthermore, stimulation of [3H]thymidine incorporation by either basic or
      acidic fibroblast growth factor was significantly reduced by lead. However, the
      leakage of lactate dehydrogenase into the medium from the cells, a marker of
      nonspecific cell damage, was not changed by lead. From these results, it was
      revealed that lead inhibits the proliferation of cultured vascular endothelial
      cells without nonspecific cell damage. Although lead does not destroy the
      monolayer of endothelial cells, the metal may exhibit its noxious effect in the
      repair process of the vascular endothelium.

PMID- 7529951
TI  - Comparative studies on the pharmacokinetics of hydrophilic
      prolinedithiocarbamate, sarcosinedithiocarbamate and the less hydrophilic
      diethyldithiocarbamate.
AB  - The pharmacokinetics of the antitoxic and anticarcinogenic compounds
      diethyldithiocarbamate, prolinedithiocarbamate and sarcosinedithiocarbamate were
      compared in rats. The bioavailability, the distribution in the organism, the
      oxidation to thiuramdisulfides, the cleavage to CS2 and the excretion in urine
      and bile were investigated. The results showed different behaviour of the three
      compounds. The more toxic diethyldithiocarbamate had a short in vivo half-life,
      was oxidized to tetraethylthiuramdisulfide in blood, and was metabolized to high
      yields of CS2 in 24 h. In contrast, prolinedithiocarbamate was more stable in
      vivo, was found predominantly in the urinary tract and was excreted in urine. The
      differences could not be explained by the presence of the carboxy group in the
      latter dithiocarbamate, since sarcosinedithiocarbamate, which also contains a
      carboxy group, behaved like diethyldithiocarbamate.

PMID- 7529955
TI  - [Benign and malignant diseases of the prostate].
AB  - Due to higher male life expectancy coupled with increasing demand for insurance
      amongst older men, diseases of the prostate are becoming more significant in life
      insurance medicine. Suitable diagnostic procedures differentiate to a large
      extent between carcinoma of the prostate gland and prostatic hyperplasia or
      prostatitis. Acute as well as chronic prostatitis can be cured and, in general,
      has no effect on life expectancy. Depending on the staging classification, benign
      prostatic hyperplasia can be treated conservatively by medication, by alternative
      heat treatment or surgical resection of the prostate. Advantages and incidence of
      complications of the different therapeutic methods are being described. The
      perioperative mortality risk as well as secondary renal complications need to be
      considered from an insurance medical point of view and may require a mortality
      loading. Only stages T1 and T2 prostatic carcinoma can be cured by surgery. New
      discoveries of the morphologic structure of the prostate gland and more
      sophisticated surgical methods in radical prostatectomy have reduced mortality.
      The incidence of post surgical complications has also decreased, when the life
      expectancy of the patient exceeds ten years. This results in a more favourable
      insurance medical assessment than that of several years ago. Stages T3 and T4
      prostatic carcinoma normally require palliative treatment. On the basis of the
      latest research, "watchful waiting" is gaining importance as against therapeutic
      concepts at the time of diagnosis. Besides the tumour staging, the presence of
      lymph node metastases or distant metastases are relevant from an insurance
      medical point of view.

PMID- 7529954
TI  - Long-term follow-up of and infectivity in blood donors with hepatitis C
      antibodies and persistently normal alanine aminotransferase levels.
AB  - BACKGROUND: Little is known about the prevalence of serum hepatitis C virus (HCV)
      RNA in blood donors with HCV antibodies and persistently normal alanine
      aminotransferase (ALT) levels. STUDY DESIGN AND METHODS: Thirty-nine anti-HCV
      positive donors with normal ALT on four determinations at 3-month intervals were
      further tested monthly for 6 months, and they had normal ALT values. The presence
      of HCV RNA was determined in these 39 donors. RESULTS: Serum HCV RNA was detected
      in 16 of 39 donors, 14 of 14 who reacted on second-generation recombinant
      immunoblot assay (RIBA-2) and 2 of 15 who were indeterminate. None of the 10 RIBA
      2-nonreactive donors had evidence of viremia. The 15 RIBA-2-indeterminate samples
      were tested with third-generation RIBA (RIBA-3); the results showed reactivity in
      5 (including the 2 HCV RNA positive), an indeterminate pattern in 7, and
      nonreactivity in 3 (all RNA negative). Among HCV RNA-positive subjects, mean age
      (p < 0.05), mean ALT (p < 0.001), signal-to-cutoff (S:CO) ratio on second
      generation enzyme-linked immunosorbent assay (p < 0.001), and gamma globulin
      levels (p < 0.05) were higher than those among HCV RNA-negative subjects. During
      6 additional months of ALT monitoring, completed by 36 of 39 donors, increased
      values were detected in 6 (5 HCV RNA positive). In 4 of those 6, however, ALT
      levels were less than 1.5-fold the upper normal limit. HCV RNA results were
      unchanged at the end of 1-year follow-up. CONCLUSION: Forty-one percent of anti
      HCV-positive donors with persistently normal ALT had active HCV infection. Long
      term ALT monitoring allowed the detection of significantly increased enzyme
      values in only 2 of 16 viremic donors. Reactivity on RIBA-2 or -3, greater age,
      mean ALT levels in the upper range of normal, higher S:CO ratio on second
      generation enzyme-linked immunosorbent assay, and higher gamma globulin levels
      were predictive of viremia.

PMID- 7529956
TI  - [Supportive therapy of pancreatic carcinoma].
AB  - Due to the progressive clinical course and unchanged poor prognosis of pancreatic
      cancer supportive therapy has to focus on improvement of the quality of life.
      Pain control is best achieved with slow release opiates and by chemoablation of
      the coeliac plexus. Furthermore, management of anorexia with megestrol acetate
      and tumor-adapted enteral and parenteral nutritional therapy are discussed. The
      treatment of chemotherapy-induced side effects with haemopoetic growth factors
      and antiemetics is dealt with as well. Finally, the therapeutic principles of the
      management of post-pancreatectomy diabetes mellitus and postoperative
      steatorrhoea are pointed out.

PMID- 7529957
TI  - [Gestational trophoblast tumors--rare, but important in general practice].

PMID- 7529959
TI  - Prostatism and the burden of benign prostatic hyperplasia on elderly men.
AB  - All men aged 40-79 years registered with two group general practices in Central
      Scotland were enumerated. Four hundred and ten men (249 in the working age group
      40-64 years and 161 in retirement ages 65-79 years satisfied predetermined
      criteria for clinical benign prostatic hyperplasia (BPH) of prostatic weight > 20
      g in the presence of urinary dysfunction and without evidence of malignancy.
      Despite a higher prevalence of BPH among the retirement group (428/1000) compared
      with men of working ages (202/1000), there were virtually no statistically
      significant differences between the two groups in terms of annoyance and
      interference in daily living activities caused by urinary dysfunction, frequency
      of urinary symptoms, or medical consultations for BPH. Although elderly men with
      BPH changed their lifestyle as a result of urinary dysfunction, only a low
      proportion of them disclosed their difficulties to a doctor. Increased education
      of the public and health care professionals about the nature and magnitude of the
      problem of BPH in elderly men is required.

PMID- 7529958
TI  - Neuropathology and immunohistochemistry of the brain-stem in neonates with
      congenital hydrocephalus: comparative studies between aqueductal stenosis and
      Arnold-Chiari malformation.
AB  - Neuropathological and immunohistochemical studies were done on the brain-stem of
      neonates who had congenital hydrocephalus with aqueductal stenosis or Arnold
      Chiari malformation (ACM). The infants with aqueductal stenosis showed
      heterogeneity in their clinicopathological findings while the infants with ACM
      were relatively similar in neuropathological findings. There were prominent
      astrogliosis, decreased immunoreactivity with antisera to tyrosine hydroxylase
      and myelin basic protein in the periaqueductal area, and an increased reactivity
      with antiserum to substance P in the tegmentum of most patients with aqueductal
      stenosis and other malformations. In ACM, there was little gliosis in the
      tegmentum and periaqueductal area and minimal immunoreactivity of tyrosine
      hydroxylase, myelin basic protein and substance P. In both groups of cases, the
      cells in the periaqueductal region differ in neurotransmitter/neuromodulator
      immunoreactivity and degree of myelination reflecting a difference possibly in
      their maldevelopment.

PMID- 7529960
TI  - Review: breast cancer in elderly patients.

PMID- 7529961
TI  - Folate deficiency inhibits pancreatic amylase secretion in rats.
AB  - Previous studies have suggested that the metabolism of methyl groups is an
      important factor in the function of the exocrine pancreas. Ethionine, an
      inhibitor of cellular methylation reactions, produces hemorrhagic pancreatitis
      when administered to mice fed a choline-deficient diet. Glycine N
      methyltransferase, an enzyme which regulates the ratio of S-adenosylmethionine to
      S-adenosylhomocysteine, is particularly abundant in the exocrine pancreas. Since
      de novo synthesis of methyl groups requires the participation of folate
      coenzymes, we investigated the effect of folate deficiency on pancreatic exocrine
      function. Rats were fed an amino acid-defined folate-deficient diet or the same
      diet supplemented with folate ad libitum. A third group received the folate
      supplemented diet pair-fed to the deficient group. After 3 and 5 wk, pancreatic
      amylase secretion was measured in perfused duodenal segments of anesthetized
      animals before and after cholecystokinin injection. Pancreatic secretion was
      significantly reduced in the deficient group compared with the pair-fed control
      group after 5 wk. These results indicate that severe folate deficiency impairs
      pancreatic exocrine function.

PMID- 7529963
TI  - Exclusion of the neuronal nitric oxide synthase gene and the human achaete-scute
      homologue I gene as candidate loci for spinal cerebellar ataxia 2.

PMID- 7529962
TI  - Is congenital bilateral absence of vas deferens a primary form of cystic
      fibrosis? Analyses of the CFTR gene in 67 patients.
AB  - Congenital bilateral absence of the vas deferens (CBAVD) is an important cause of
      sterility in men. Although the genetic basis of this condition is still unclear,
      it has been shown recently that some of these patients carry mutations in their
      cystic fibrosis transmembrane conductance regulator (CFTR) genes. To extend this
      observation, we have analyzed the entire coding sequence of the CFTR gene in a
      cohort of 67 men with CBAVD, who are otherwise healthy. We have identified four
      novel missense mutations (A800G, G149R, R258G, and E193K). We have shown that 42%
      of subjects were carriers of one CFTR allele and that 24% are compound
      heterozygous for CFTR alleles. Thus, we have been unable to identify 76% of these
      patients as carrying two CFTR mutations. Furthermore, we have described the
      segregation of CFTR haplotypes in the family of one CBAVD male; in this family
      are two male siblings, with identical CFTR loci but displaying different
      phenotypes, one of them being fertile and the other sterile. The data presented
      in this family, indicating a discordance between the CBAVD phenotype and a marked
      carrier (delta F508) chromosome, support the involvement of another gene(s), in
      the etiology of CBAVD.

PMID- 7529966
TI  - T-cell receptor alpha and beta chain gene expression in cells infiltrating human
      cardiac allografts.
AB  - Intragraft T-cell receptor (TCR) alpha and beta chain variable region gene
      expression was analyzed in human cardiac allograft biopsies by reverse
      transcription polymerase chain reaction. Rearranged TCR alpha and beta chain gene
      transcripts were detected in all biopsies examined (N = 23), indicating the
      presence of T cells bearing the alpha/beta TCR even in the absence of
      microscopically apparent leukocyte infiltration. In this analysis, a broad TCR
      alpha/beta repertoire in actively rejecting lesions was demonstrated, whereas
      fewer TCR alpha and beta chain gene families were detected in nonrejecting
      lesions. The number of expressed TCR V beta chain gene families typically was two
      to sixfold higher than that of V alpha chain families in all biopsies tested.
      This asymmetric relation was present throughout the histologic grading spectrum
      of the biopsies. Based on these data, the TCR repertoire is heterogenous even in
      the early stages of mononuclear cell infiltration of the allograft. Also based on
      the data, the presence of T cells in grafts with minimal cellular infiltrates is
      not a specific marker of subsequent rejection episode, because T cells were
      identified in all allograft biopsies.

PMID- 7529967
TI  - Chemokines as allergic mediators--relationship to histamine-releasing factors.

PMID- 7529965
TI  - Insulin-like growth factors: clinical experience in ovarian function.
AB  - Insulin, insulin-like growth factor, and insulin-like growth factor binding
      proteins have been shown to play major roles in the modulation of both normal and
      disturbed ovarian physiology. Identification of many of the actions of these
      peptides was initially characterized using animal models. However, an increasing
      body of evidence has emerged to clarify their contributions in human reproductive
      function. It is clear that at various stages of folliculogenesis, local steroid
      production acts in concert with intraovarian peptides to promote dominant
      follicle development. This review will discuss the physiologic role(s) of the
      insulin-insulin-like growth factor-insulin-like growth factor binding protein
      family in reproductive function and disorders of androgen excess.

PMID- 7529968
TI  - Liver of juvenile Atlantic salmon, Salmo salar L.: a light, transmission, and
      scanning electron microscopic study, with special reference to the sinusoid.
AB  - BACKGROUND: This report provides a detailed description of sinusoidal and
      perisinusoidal structures in the normal liver of the juvenile Atlantic salmon
      (Salmo salar L.), a teleost species. METHODS: The liver was studied by light,
      transmission, and scanning electron microscopy, and organ specimens were sampled
      after retrograde, whole-body perfusion through the dorsal aorta using 3%
      glutaraldehyde. Detailed characterization of perisinusoidal stellate cells also
      included immunohistochemical staining for desmin and evaluation of
      autofluorescence of the same cells upon excitation in ultraviolet (UV) light.
      RESULTS: The sinusoid is lined by one cell type only: the endothelial cell. No
      intraluminal pit cells or Kupffer cells are present. The space of Disse contains
      reticulin fibres, visualized by Gomori's silver stain, and perisinusoidal
      stellate cells (PSC). PSC exhibited autofluorescence in UV light, indicating that
      these cells store vitamin A in cytoplasmic lipid droplets. Immunohistochemically,
      PSC were found negative for desmin. The space of Disse, extending deep down
      between adjacent hepatocytes, receives long, slender microvilli from parenchymal
      cells. In addition to scattered macrophages, interhepatocytic cells (IHC) are
      found perisinusoidally. Hepatocytes of Atlantic salmon form branching and
      anastomosing tubules. CONCLUSIONS: The sinusoids of Atlantic salmon liver are
      lined by a fenestrated endothelium, with PSC located in the space of Disse, with
      macrophages and IHC as inhabitants of the interhepatocytic space. IHC show
      ultrastructural similarities to mammalian pit cells and teleostean large granular
      lymphocytes, as well as to piscine monocytes. PSC might be storage cells for
      vitamin A in Atlantic salmon as shown by autofluorescence in these cells, while
      immunohistochemical studies indicate that desmin does not seem to be an adequate
      immunohistochemical marker for PSC in the juvenile Atlantic salmon.
      Methodologically, fixation for electron microscopy was performed by a new and
      convenient perfusion method: arterial retrograde whole body perfusion. Liver
      specimens intended for scanning electron microscopy were fractured at room
      temperature after prolonged osmium postfixation, leaving hepatocytes intact and
      producing images well suited to document the three-dimensional structure of cells
      and tissue.

PMID- 7529964
TI  - Novel mutations and deletions of the KIT (steel factor receptor) gene in human
      piebaldism.
AB  - Piebaldism is an autosomal dominant genetic disorder of pigmentation
      characterized by white patches of skin and hair. Melanocytes are lacking in these
      hypopigmented regions, the result of mutations of the KIT gene, which encodes the
      cell surface receptor for steel factor (SLF). We describe the analysis of 26
      unrelated patients with piebaldism-like hypopigmentation--17 typical patients, 5
      with atypical clinical features or family histories, and 4 with other disorders
      that involve white spotting. We identified novel pathologic mutations or
      deletions of the KIT gene in 10 (59%) of the typical patients, and in 2 (40%) of
      the atypical patients. Overall, we have identified pathologic KIT gene mutations
      in 21 (75%) of 28 unrelated patients with typical piebaldism we have studied. Of
      the patients without apparent KIT mutations, none have apparent abnormalities of
      the gene encoding SLF itself (MGF), and genetic linkage analyses in two of these
      families are suggestive of linkage of the piebald phenotype to KIT. Thus, most
      patients with typical piebaldism appear to have abnormalities of the KIT gene.

PMID- 7529969
TI  - The alpha-sympathomimetic midodrin as a tool for diagnosis and treatment of sperm
      transport disturbances.
AB  - The present study was performed to determine the usefulness of the alpha
      sympathomimetic midodrin for diagnosis and treatment of functional sperm
      transport disturbances. 140 andrological patients consulting due to severe
      oligozoospermia, hypospermia or partial/complete retrograde ejaculation were
      included. Ejaculates were examined 30 min after intravenous injection of 5-15 mg
      midodrin. Sperm concentration, motility and alpha-glucosidase as a marker of both
      epididymal function and sufficient passage through the vasa deferentia and the
      ejaculatory duct were measured and the values compared to those in the ejaculates
      obtained before therapy. In 23 of 140 patients, sperm concentration or total
      sperm count was improved by more than 10 million spermatozoa ml-1 or 20 million
      spermatozoa per ejaculation. Alpha-glucosidase in the seminal plasma increased in
      two cases. The present study demonstrates that severe oligozoospermia may be
      caused by functional transport disturbance of semen from the epididymis to the
      efferent duct system. In these cases, midodrin is of diagnostic and therapeutic
      value; however, it should be emphasized that its effectiveness cannot be
      predicted individually.

PMID- 7529970
TI  - [The esthetics of Leonardo Da Vinci in light of Freud's research].

PMID- 7529971
TI  - Neuromodulation of fever. A possible role for substance P.

PMID- 7529972
TI  - Cytochrome P450 arachidonic acid omega-hydroxylation in the proximal tubule of
      the rat kidney.
AB  - 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) is a major cytochrome P450
      dependent arachidonate metabolite in the rat kidney. In the present study we
      characterized the formation of 20-HETE in the proximal tubule, the nephron
      segment with the highest concentration of cytochrome P450 activities, including
      P450 arachidonic acid metabolism. Freshly isolated tubules showed a basal
      formation of 20-HETE, implying that it is an endogenous constituent of the
      proximal tubule. Conversion of exogenous arachidonic acid to 20-HETE in proximal
      tubule homogenates was enzymatic and NADPH-dependent (i.e., 0 and 65.5 +/- 1.1
      pmol/mg/min in the absence and presence of NADPH, respectively). That its
      formation was not affected by indomethacin but inhibited following preincubation
      with 17-ODYA (17-octadecynoic acid) and 7-ER (7-ethoxyresorufin) suggested that a
      P450 monooxygenase activity was involved in its synthesis. This was further
      strengthened by the demonstration that antibody raised against the rat cytochrome
      P450 4A1, a major fatty acid omega-hydroxylase isozyme, inhibited 20-HETE
      formation, suggesting the involvement of a P450 4A1 or P450 4A1-like activity in
      this reaction. Pretreatment of rats with clofibrate and dexamethasone, inducers
      of the P450 4A gene family, yielded a twofold increase in the proximal tubular
      synthesis of 20-HETE as well as an increase in P450 4A1 mRNA. These results,
      together with previous demonstrations that 20-HETE vasoconstricts isolated blood
      vessels, namely, renal microvessels, and affects tubular ion transport, suggest a
      role for 20-HETE in the regulation of renal vascular tone and transport functions
      and further stress the importance of understanding the regulation of 20-HETE
      synthesis in the kidney.

PMID- 7529974
TI  - Lipocortin 1 and hypothalamo-pituitary function in the rat.

PMID- 7529973
TI  - Steroid receptor-mediated modulation of CD4+CD62L+ cell homing. Implications for
      drug abusers.
AB  - Naive human T cells home to peripheral lymph nodes via the leukocyte endothelial
      cell adhesion molecule-1 (LECAM-1, l-selectin, CD62L, Leu8 antigen) they express.
      We enriched populations of CD4+CD62L+ cells (attachment of Leu8+ T cells to
      flasks coated with anti-mouse IgG (AIS); Leu8+ T cells, 82.3% pure (+/- 2.3%),
      enriched for CD4+ cells by incubation over flasks coated with anti-CD4 antibody-
      this 3-4-day procedure yields an 88 +/- 1.4% recovery. Cells were treated with
      dexamethasone in vitro for 24-48 h, and monitored by flow cytometry. We found
      severe toxicity by this steroid at high concentration (10(-6) M: 35% decrease in
      CD62L+ T cells, 22% drop specifically in CD4+CD62L+ cells), suggesting the onset
      of receptor-mediated apoptotic events. The toxicity was dose dependent (5% and 7%
      drop in CD62L+ T and CD4+CD62L+ cells, respectively, at 10(-9) M, the
      concentration found in plasma 10 h following the administration of 1 mg
      dexamethasone). One mg of dexamethasone given to normal subjects leads to a 15
      20% decrease in circulating CD4+CD62L+ cells at 10 h. This tends to be correlated
      with a drop in the number of glucocorticoid cytosolic receptors. Thus, steroids
      seem to modulate CD4+CD62L+ cell homing by means of receptor-mediated mechanisms.

PMID- 7529975
TI  - Glucocorticoid negative feedback in pituitary corticotropes. Pivotal role for
      calcineurin inhibition of adenylyl cyclase.

PMID- 7529976
TI  - The molecular phylogeny and systematics of the actinomycetes.
AB  - Sequences of 16S ribosomal RNA have provided actinomycetologists with a
      phylogenetic tree that allows the investigation of the evolution of actinomycetes
      and also provides a basis for classification. The origin of actinomycetes and,
      except for bifidobacteria, the order by which the main sublines evolved, cannot
      yet be determined with certainty. However, calibration of rRNA sequence
      divergence with palaeochemical data, and previously published substitution rates
      of endosymbiotic bacteria, suggest that the main radiation occurred less than 1
      billion years ago. Within this radiation, several phylogenetically homogeneous,
      but sometimes phenotypically heterogeneous, clades appear to have diverged over a
      short evolutionary period. The resolution of the 16S rRNA molecule appears to be
      insufficient to clearly determine the branching patterns between clades in this
      area of the phylogenetic tree. The distribution of some morphological and
      chemotaxonomic traits such as types of peptidoglycan, menaquinone, phospholipids,
      cell wall sugars, and fatty acids facilitate the phenotypic delineation of genera
      within each clade. At higher taxonomic levels, e.g. at the family level,
      phenotypic similarities are unpredictable and tend to be less conserved. With the
      exception of mycolic acids, most traits are polyphyletic--hence they are
      unreliable indicators per se of phylogenetic relationships. Nevertheless,
      combinations of phenotypic properties are invaluable for predicting whether a new
      organism is likely to be a member of an established or a novel taxon. Current
      knowledge about the phylogenetic structure of the actinomycetes provides not only
      a sound basis for future taxonomic work but also a framework for the rational
      exploration of their ecology and biotechnological potential.

PMID- 7529977
TI  - HIV-1 tat acts as a growth factor and induces angiogenic activity in BK virus/tat
      transgenic mice.

PMID- 7529978
TI  - [Complete remission by cytarabine ocfosfate plus G-CSF therapy in a patient with
      hypoplastic RAEB-T].

PMID- 7529979
TI  - [Treatment of adult T-cell leukemia].
AB  - The treatment strategy for adult T-cell leukemia has not been established. CHOP
      derived combination chemotherapy protocols such as VEPA and VEPAM have failed to
      yield high complete remission rates and long survivals. Second or third
      generation combination chemotherapy regimens using alternative non-cross
      resistant drugs also have not achieved satisfactory results. A new multi
      institutional trial attempting to increase dose intensity supported by
      granulocyte colony-stimulating factor is bringing improved remission rates and
      survival times. Other strategies using autologous bone marrow or peripheral blood
      progenitor cells should be studied as a next step.

PMID- 7529980
TI  - [Chemotherapy of malignant melanoma].
AB  - At present, the chemotherapeutic combinations for melanoma available are three
      regimens using DAV, PAV and CDV. Among of them, the DAV combination (dacarbazine,
      ACNU, vincristine) and PAV (peplomycin, ACNU, vincristine) are used as post
      operative adjuvant therapy for stage II and III patients. Their aim is to prevent
      recurrence and prolong survival. For stage IV patients, the major therapeutic
      procedure is a CDV combination (cisplatin, dacarbazine, vindesine). Adoptive
      immunotherapy is almost always used for patients with distant metastases. They
      have shown comparable effects for metastatic lesion in the lymph nodes, mucous
      membrane, brain and lung. Excellent results were obtained in patients having skin
      metastases by intratumoral injection of interferon-beta. Studies on new drugs and
      their combinations must be undertaken for more effective treatment of malignant
      melanoma.

PMID- 7529983
TI  - Carbon monoxide poisoning in two children riding in the back of a van.

PMID- 7529982
TI  - Mitochondrial DNA 8993 (NARP) mutation presenting with a heterogeneous phenotype
      including 'cerebral palsy'.
AB  - The mitochondrial DNA (mtDNA) mutation 8993 is an important cause of Leigh's
      encephalopathy. A family is reported where other affected members have presented
      with non-specific delayed development or cerebral palsy. The diagnosis should be
      considered not only in children with Leigh's encephalopathy, but also in those
      with mild neurological dysfunction (including cerebral palsy) if there is a
      pigmentary retinopathy or a family history of neurological or ophthalmological
      disease. There was some correlation in this family between the disease severity
      and the proportion of mutant mtDNA in the blood. This mutation appears to
      segregate to high levels of mutant mtDNA rapidly within pedigrees and the mother
      of a severely affected child has a high risk of having further children with a
      high proportion of mutant mtDNA and a severe phenotype.

PMID- 7529984
TI  - Quality of life in surgically palliated complex congenital heart disease.

PMID- 7529981
TI  - The insulin-like growth factor axis and collagen turnover during prednisolone
      treatment.
AB  - Serum concentrations of insulin-like growth factor I (IGF-I) and insulin-like
      growth factor binding protein 3 (IGFBP-3), the carboxyterminal propeptide of type
      I collagen (PICP), the carboxyterminal pyridinoline crosslinked telopeptide of
      type I collagen (ICTP), and the aminoterminal propeptide of type III procollagen
      (PIIINP) were studied in 10 prepubertal children with asthma (mean age 9.0
      years). The children were treated with 2.5 and 5.0 mg/day prednisolone in a
      randomised double blind crossover trial with run in, treatment, and washout
      periods of two weeks. No statistically significant effects on serum
      concentrations of IGF-I and IGFBP-3 were found. Dose related reductions of PICP,
      ICTP, and PIIINP were observed: the mean (SEM) reduction in PICP was 33.4 (26.3)
      and 68.4 (20.6) micrograms/l, in ICTP 2.5 (0.5) and 2.9 (0.6) micrograms/l, and
      in PIIINP 2.1 (0.7) and 3.1 (1.8) micrograms/l during the 2.5 and 5.0 mg
      prednisolone periods respectively. Short term treatment with low daily doses of
      prednisolone is associated with suppression of serum markers of type I and III
      collagen turnover in children with asthma. Intermediate and long term effects
      remain to be studied.

PMID- 7529985
TI  - Expression of CD44 in normal and rheumatoid synovium and cultured synovial
      fibroblasts.
AB  - OBJECTIVE: To determine if expression of CD44, the principal receptor for
      hyaluronan, was altered in rheumatoid (RA) synovium and cultured rheumatoid
      synovial fibroblasts. METHODS: Synovium was obtained from normal adult human
      joints (n = 4) and from joints of patients with RA (n = 5). Specific monoclonal
      antibodies to CD44 were used in immunofluorescence of whole synovium and cultured
      synovial fibroblasts and in quantitative Western blotting and ELISA of CD44 in
      cultured synovial fibroblasts. RESULTS: CD44 was restricted to the lining layer
      in normal synovium but present, in reduced concentrations, throughout rheumatoid
      synovium. Cultured rheumatoid cells were 19% larger in area and showed far fewer
      and less extensive CD44-positive cytoplasmic extensions, together with reduced
      staining intensity compared with normal. Quantitative Western blotting normalised
      for cell protein showed a 75% reduction (normal = 1754 (835), rheumatoid = 409
      (84) mean (SD) arbitrary units) in the amount of CD44 in rheumatoid cells
      compared with normal, and enzyme linked immunosorbent assay (ELISA) of cultured
      cell monolayers normalised for cell number indicated a 29% reduction (normal =
      0.707 (0.110), rheumatoid = 0.504 (0.103), mean (SD) optical density at 405 nm).
      CONCLUSIONS: Rheumatoid synovial cells showed altered morphology and reduced CD44
      expression compared with normal cells. CD44, by means of modulated associations
      with the cytoskeleton, may be involved in cell shape change.

PMID- 7529986
TI  - Immunoblotting detection of so-called 'antikeratin antibodies': a new assay for
      the diagnosis of rheumatoid arthritis.
AB  - OBJECTIVES: To assess the diagnostic value for rheumatoid arthritis (RA), of an
      immunoblotting assay based on the rat oesophagus epithelium antigens recognised
      by the so-called 'antikeratin antibodies' ('AKA'), antigens that have been
      identified as three non-cytokeratin proteins (referred to as A, B and C
      proteins). METHODS: After polyacrylamide gel electrophoresis in non-denaturing
      conditions and electrotransfer of an epithelial extract, the immunoreactivities
      to the A, B and C proteins of a series of serum samples from 88 patients with RA
      and 100 patients with non-rheumatoid rheumatic diseases, were semiquantitatively
      evaluated. RESULTS: A total of 81.8% of RA serum samples recognised the three
      proteins, while 91% of non-RA serum samples only weakly recognised the A and B
      proteins but not the C protein. Only in the group of RA patients, were the titres
      of the antibodies to the A, B and C proteins found to be significantly correlated
      with each other and with the titres of 'AKA' detected by the standard indirect
      immunofluorescence (IIF) method. For a diagnostic specificity of 99%, the
      diagnostic sensitivities of the detection of the A and B proteins were 50% and
      43.2%, respectively, when those of the detection of 'AKA' by IIF and of IgM
      rheumatoid factor by enzyme-linked immunosorbent assay were 42% and 54%,
      respectively. In contrast, at a same specificity of 99%, the diagnostic
      sensitivity of the detection of the C protein was significantly higher with a
      value of 70.5%. CONCLUSION: This immunoblotting assay which is the first
      immunochemical method proposed for the detection of 'AKA, should be validated on
      larger series of patients but can already be considered as a very powerful test
      for the serological diagnosis of RA.

PMID- 7529987
TI  - Lysosomal enzyme secretion into pancreatic juice in rats injected with pancreatic
      secretagogues and augmented secretion after short-term pancreatic duct
      obstruction.
AB  - To examine the possible secretion of lysosomal enzymes into the pancreatic juice
      in rats stimulated with pancreatic secretagogues under both physiological and
      pathological conditions, we investigated the changes in the secretion of
      cathepsin B, as a lysosomal enzyme, into pancreatic juice with stimulation of 5
      different doses (0.1, 0.2, 0.5, 1.0, and 1.5 micrograms/kg.hr) of caerulein.
      Control rats had only pancreatic duct cannulation. In other rats, the pancreatic
      duct was obstructed for 3 hours and secretin was infused (0.2 CU/kg.hr).
      Caerulein stimulated the secretion of cathepsin B into the pancreatic juice in a
      dose-dependent manner, as in amylase secretion, and caerulein in higher doses
      (1.0 and 1.5 microgram/kg.hr) inhibited cathepsin B output as it did amylase
      output. There was a significantly high positive correlation between cathepsin B
      output and amylase output after stimulation with caerulein. The secretion of
      several other lysosomal enzymes was also stimulated by caerulein. Blockage of the
      pancreatic duct for 3 hours caused a significant but moderate rise in serum
      amylase levels. Redistribution of cathepsin B activity in the pancreatic
      subcellular fractions was noted with an increase in the amount of cathepsin B
      recovered from zymogen-rich pellets after 15 min of centrifugation at 1300 x g.
      These changes after temporary pancreatic duct obstruction are very similar to
      those previously noted during the early stage of diet-and caerulein-induced
      experimental pancreatitis and suggest colocalization of lysosomal enzymes and
      digestive enzymes. In addition, in duct obstructed rats, the secretion of
      cathepsin B and other lysosomal enzymes stimulated by caerulein was significantly
      greater than in animals with free-flowing pancreatic juice. These results
      indicate that lysosomal enzymes are secreted into pancreatic juice after
      stimulation by gut hormones in the same manner as classical pancreatic digestive
      enzymes such as amylase. Moreover, lysosomal enzymes which colocalize with
      zymogen granules in rats with short-term pancreatic duct obstruction are also
      secreted into pancreatic juice together with digestive enzymes after stimulation
      with gut hormones. These findings suggest that lysosomal enzymes are present in
      zymogen granules under normal conditions and that they may play
      pathophysiological roles in pancreatic juice. They also contribute to an
      understanding of the pathogenesis of pancreatitis, since cathepsin B can activate
      trypsinogen.

PMID- 7529988
TI  - [Early severe malnutrition and psychomotor development. Effects of a
      rehabilitation program].
AB  - This study evaluates the psychomotor development of 228 undernourished infants
      submitted to an integral rehabilitation program in Nutritional Recovery Centers.
      At admission these children present a moderate retardation of their developmental
      quotient: mean 0.59 +/- 0.17, improving significantly to mean 0.79 +/- 0.4 (p <
      0.001) after an average period of 178.2 +/- 63.9 days of intervention. As regards
      areas of development, rehabilitation only demonstrates a significant change in
      coordination and language, not so in the social and motor areas. Those children
      presenting the most severe developmental delays are also those who obtain the
      greater benefits from this integral rehabilitation program.

PMID- 7529989
TI  - Localization of four antigenic sites involved in Venezuelan equine
      encephalomyelitis virus protection.
AB  - Stable neutralization and protection escape variants of a virulent strain
      (Trinidad Donkey) of the VEE virus were selected by monoclonal antibodies (MAbs).
      Determination of nucleotide sequences of nine variants revealed a clustering of
      single mutations in four regions of the E1 and E2 glycoproteins. Involvement of
      amino acid residues 206 (site E1-1), 57 and 59 (site E2-2), 180, 182, 213, 214
      and 216 (site E2-6) and 232 (site E2-3) in protective epitopes was demonstrated.

PMID- 7529990
TI  - Rapid characterization of new pestivirus strains by direct sequencing of PCR
      amplified cDNA from the 5' noncoding region.
AB  - Reverse transcription coupled with the polymerase chain reaction (RT-PCR) was
      used for the rapid laboratory diagnosis of pestivirus infections. A direct DNA
      sequencing method was developed for the analysis of the amplified cDNA from the
      5' noncoding region of the viral genome. 70 pestivirus strains were compared in
      this study. Sequence analysis allowed the characterization of each isolate as
      either classical swine fever virus (CSFV), bovine viral diarrhea virus, or border
      disease virus, respectively. The 48 CSFV strains could be further classified into
      several subgroups, which correlated either with the geographical origin or the
      date of the first isolation of the respective isolate.

PMID- 7529991
TI  - Effects of insertion of multiple AP-1 binding sites into the U3 region of the
      long terminal repeat of feline immunodeficiency virus.
AB  - An oligonucleotide containing multiple AP-1 binding sites was introduced into the
      regulatory sequence in the long terminal repeat (LTR) of feline immunodeficiency
      virus (FIV). Chloramphenicol acetyltransferase assay revealed that basal promoter
      activity of the mutated LTR was higher than that of the wild-type LTR in Crandell
      feline kidney (CRFK) cells. The mutated LTR was introduced into an infectious
      molecular clone of FIV and the clone was transfected into CRFK cells. The virus
      production of the mutant in the cells was as high as that of the wild-type when
      determined by the reverse transcriptase activity assay. The growth of the mutant
      virus obtained from the transfected CRFK cells was examined in feline T
      lymphoblastoid cell lines (MYA-1 and FeL-039 cells) and primary feline peripheral
      blood mononuclear cells (fPBMCs). The growth was delayed when compared with that
      of the wild-type virus in all the cells used. Upon examination by polymerase
      chain reaction, the length of the LTR of the mutant virus was shortened in both
      MYA-1 cells and fPBMCs. Sequence analysis revealed that the insertion was
      completely deleted 39 days after infection in the MYA-1 cells.

PMID- 7529992
TI  - Concentration of live retrovirus with a regenerated cellulose hollow fiber, BMM.
AB  - A concentrated live retrovirus is required for in vitro experiments. A
      cuprammonium-regenerated cellulose hollow fiber, termed BMM, originally developed
      for biohazardous viral removal, was used to concentrate two different
      retroviruses, an ecotropic murine leukemia virus (MuLV) and human
      immunodeficiency virus (HIV). The BMM was useful for concentrating live virus
      suspension 10- to 30-fold from 500-1000 ml of culture supernatant. The ecotropic
      MuLV concentrated by BMM was demonstrated to be viable and biologically intact by
      XC plaque-forming assay and reverse transcriptase assay. The concentrated MuLV
      reached a much higher titer in the spleen in mice than the original one. The
      virus concentration assessed by p24 antigen for HIV was clearly higher than that
      of the original culture supernatant of HIV-infected cell lines. Since BMM hollow
      fibers trapped viruses by the sieving mechanism but not by adsorption, the viral
      particles were recovered by washing and the total live virus recovery rate was
      high, about 50%. Furthermore 60 min sufficed to handle 1000 ml of supernatant in
      the case of a filtration area of 0.03 m2. These results show that the BMM
      provides us with a rapid, safe and efficient method for concentrating live
      retroviruses.

PMID- 7529993
TI  - Laser photocoagulation for neovascular lesions nasal to the fovea. Results from
      clinical trials for lesions secondary to ocular histoplasmosis or idiopathic
      causes. Macular Photocoagulation Study Group.
AB  - OBJECTIVE: To determine whether laser photocoagulation of peripapillary choroidal
      neovascularization (CNV) or large neovascular lesions that are located nasal to
      the fovea is beneficial with respect to preservation of remaining vision-
      consistent with the overall study findings. PATIENTS AND INTERVENTIONS: A total
      of 113 eyes (112 patients) having either peripapillary CNV or CNV that was
      located nasal to the fovea and larger than 750 microns in longest diameter
      associated with either ocular histoplasmosis or idiopathic causes were identified
      from the eyes that were randomly assigned to either laser photocoagulation or
      observation only in clinical trials conducted by the Macular Photocoagulation
      Study Group. MAIN OUTCOME MEASURES: Visual acuity and change in visual acuity
      from baseline examination were compared for laser-treated and untreated eyes.
      RESULTS: At the 3-year examination, 11% (6/54) of the treated eyes vs 41% (21/51)
      of the untreated eyes had lost six or more lines of visual acuity (P < .001).
      Among eyes with peripapillary lesions, 14% (3/22) of the treated eyes vs 26%
      (6/23) of the untreated eyes had lost six or more lines of visual acuity at the 3
      year examination (P = .29). Among eyes with nasal lesions, 9% (3/32) of the
      treated eyes vs 54% (15/28) of the untreated eyes had lost six or more lines of
      visual acuity at the 3-year examination (P < .001). CONCLUSION: Results from the
      subset of patients who had extrafoveal or juxtafoveal peripapillary CNV or CNV
      that was located nasal to the fovea were consistent with the beneficial results
      of treatment observed in the entire group of eyes that were studied by the
      Macular Photocoagulation Study Group.

PMID- 7529994
TI  - Pancreatic acinar-cell desensitization alters InsP3 production and Ca2+
      mobilization under conditions where InsP3 receptor remains intact.
AB  - Desensitization of rat pancreatic acinar cells with 0.1 mM carbamoylcholine (Cch)
      or 0.5 nM caerulein (CAE), a cholecystokinin (CCK) agonist, altered the
      subsequent secretory responses to these two agonists. Changes in receptor
      affinities, shifts in receptor populations, receptor internalization and
      phosphorylation are the major modifications affecting the muscarinic and CCK
      receptors in response to desensitization. In this study, post-receptor
      alterations were examined in order to explain the altered enzyme secretion. Cch
      or CAE desensitization resulted in decreased Ca2+ release in response to CAE and
      Cch respectively. Under desensitizing conditions, the biochemical and
      pharmacological properties of the InsP3 receptor were not affected. Control and
      desensitized acini had similar Bmax. and KD values. The Ca(2+)-channel property
      of the InsP3 receptor was not affected, either, since Ca2+ release in response to
      increasing concentrations of InsP3 remained comparable in both groups of saponin
      permeabilized acini. Finally, the quantities of InsP3 formed in response to Cch
      and CAE, measured by InsP3 radioreceptor assay, were significantly decreased in
      the Cch- and CAE-desensitized groups, and these decreases were not due to
      increased InsP3 turnover. These new data indicate that desensitization of acinar
      cells with Cch and CAE causes post-receptor modifications resulting in decreased
      InsP3 formation and decreased intracellular Ca2+ mobilization. It is suggested
      that the attenuated Ca2+ response is related to a decreased formation of InsP3
      from PtdInsP2 hydrolysis and that phospholipase C could be the immediate target
      of this regulation.

PMID- 7529995
TI  - Time-dependent inhibition of peptidylprolyl cis-trans-isomerases by FK506 is
      probably due to cis-trans isomerization of the inhibitor's imide bond.
AB  - Free in solution, the immunosuppressive compounds cyclosporin A (CsA), FK506,
      ascomycin and rapamycin are present in many solvents in various slowly
      interconverting conformations. Together with their cellular receptor proteins,
      cyclophilin (CyP) and FK506-binding protein (FKBP), however, these inhibitors
      have been shown to have a homogeneous conformation. The existence of a slow cis
      trans interconversion of an imidic bond in the inhibitor molecule during the
      course of the formation of the CsA-CyP18cy complex (where CyP18cy is human 18 kDa
      cytosolic CyP) prompted us to investigate the reaction of the peptidomacrolides
      FK506, ascomycin and rapamycin with two specific binding-proteins in more detail.
      Since formation of the FK506-FKBP complex results in the inhibition of the
      peptidylprolyl cis-trans-isomerase activity of the binding protein, we used the
      enzyme's decrease in enzymic activity to monitor binding of the inhibitors to
      their enzyme targets. For FK506, the kinetics of inhibition of human 12 kDa
      cytosolic FKBP (FKBP12cy) were clearly dependent on time. Subsequent to a rapid
      inactivation reaction, not resolved in its kinetics due to manual mixing, a slow
      dominant first-order inactivation process with a relaxation time of 1163 s at 10
      degrees C was observed. Concomitantly the Ki value of the slow phase dropped 2.6
      fold within the first 60 min of incubation. Using the FKBP12cy homologue 25 kDa
      membrane FKBP (FKBP25mem), a bacterial peptidylprolyl cis-trans-isomerase, the
      rate and amplitudes of the inhibition reactions were very similar to FKBP12cy. On
      the other hand, the kinetics and amplitudes of the inhibition of FKBP12cy varied
      significantly if rapamycin was used as an inhibitor instead of FK 506. Owing to
      reduced conformation transition in rapamycin upon binding to FKBP12cy, the slow
      phase during inhibition was significantly decreased in amplitude. A likely reason
      for this became apparent when the activation-enthalpy and the pH-dependence of
      the rate constants of the slow phase were determined. We conclude that the cis to
      trans interconversion of the pipecolinyl bond of the three peptidomacrolides may
      be responsible for the slow process. There was no indication of a suicide
      catalysis of this process by FKBPs.

PMID- 7529996
TI  - Identification of an immunodominant functional domain on human CD36 antigen using
      human-mouse chimaeric proteins and homologue-replacement mutagenesis.
AB  - The human CD36 antigen is a multifunctional membrane glycoprotein that acts as a
      receptor for thrombospondin, malaria-infected erythrocytes and oxidized low
      density lipoprotein, as well as being implicated in the recognition of apoptotic
      neutrophils by macrophages. OKM5 and other anti-CD36 monoclonal antibodies have
      been shown to inhibit these CD36 adhesive functions, suggesting that the
      monoclonal-antibody epitopes and the domains that mediate these events are
      closely related. Analysis of a series of chimaeric exchanges between human and
      mouse CD36 shows that six anti-CD36 monoclonal antibodies (OKM5, FA6-152, L103,
      5F1, SM phi and 10/5) recognize epitopes within the domain comprising amino acids
      155-183. A seventh monoclonal antibody (13/10) binds to another domain that spans
      amino acids 30-76. Homologue-replacement mutagenesis performed within the human
      155-183 immunodominant sequence identifies key residues for the binding of three
      functional monoclonal antibodies (OKM5, FA6-152 and L103). The fact that
      antibodies directed against the 155-183 domain can inhibit adhesion suggests that
      this domain is directly involved in CD36-ligand binding.

PMID- 7529999
TI  - Possible involvement of protein kinase C and low molecular weight GTP-binding
      proteins in thrombin-induced histamine secretion in human platelets.
AB  - Thrombin and 12-O-tetradecanoylphorbol 13-acetate (TPA) caused histamine
      secretion from human platelets. To clarify the intracellular signalling mechanism
      of thrombin-induced histamine secretion, the effects of pertussis toxin (PTX) and
      botulinus toxin (BTX) on thrombin- and TPA-induced histamine secretion were
      examined in human platelets. The secretion by thrombin was sensitive to BTX, but
      not PTX. The secretion by TPA was also inhibited by BTX. These results suggest
      that protein kinase C and low molecular weight G-proteins sensitive to BTX are
      involved in histamine secretion.

PMID- 7529998
TI  - Nuclear factor-kappa B mediates induction of vascular cell adhesion molecule-1 in
      glomerular mesangial cells.
AB  - Cultured glomerular mesangial cells (GMCs) can be activated at the
      transcriptional level by a variety of physiologically relevant factors including
      cytokines, endotoxin and glycosylated end products. The mechanism with which the
      signal is transduced from the membrane to the nucleus of these cells is largely
      unclear. In vascular endothelial cells, the signal transduction pathway involves
      activation of the pleuripotent transcription factor, NF-kappa B, and leads to
      increased expression of a variety of genes including vascular cell adhesion
      molecule-1 (VCAM-1). Here, we demonstrate that TNF-alpha and IL-1 beta
      transiently induced VCAM-1 mRNA expression in a time dependent manner. TNF-alpha
      also induced the specific interaction of proteins from GMC nuclei with an
      oligonucleotide bearing the NF-kappa B binding sites in the VCAM-1 promoter.
      Electrophoretic mobility shift and supershift analysis indicated that the p65
      subunit of NF-kappa B is a component of this induced complex. Finally, reporter
      activity driven by a VCAM-1 promoter-chloramphenicol acetyltransferase reporter
      construct increased 8-10 fold following TNF-alpha incubation, or p65
      cotransfection. Thus, the p65 subunit of NF-kappa B is activated in GMCs exposed
      to cytokine and can mediate induction of gene expression.

PMID- 7529997
TI  - Stopped-flow fluorescence kinetics of bovine alpha 2-antiplasmin inhibition of
      bovine midiplasmin.
AB  - In the conversion of bovine plasminogen to bovine plasmin not only the expected
      urokinase-catalysed cleavage of Arg-557-Val-558, and the following autocatalytic
      cleavage separating the N-terminal peptide 1-77 from the heavy chain of plasmin,
      but also a cleavage at Arg-342-Met-343 between kringles 3 and 4 is seen. Here,
      kinetic studies of the interaction of bovine alpha 2-antiplasmin with bovine
      plasmin were performed on isolated bovine midiplasmin (lacking kringles 1-3) and
      on bovine plasmin containing all of the activation products from the bovine
      plasminogen. A series of experiments using stopped-flow fluorescence fast
      kinetics as well as conventional techniques suggests a reaction model in
      accordance with the one known for the human system. First, a tight complex (K1 in
      the nanomolar range) is formed in a fast reaction step; and second, a tightening
      of this complex occurs in a slow reaction step. The final complex is indeed so
      tight (Ki < or = pM), that the reaction for many practical purposes is
      legitimately considered irreversible. The stopped-flow method allows for the
      determination of reliable values of the second-order rate constant for the fast
      association step. At pH 7.4 and 25 degrees C, k+1 = 1.7 x 10(6) M-1 s-1 was
      obtained in the absence and k+1 = 0.9 x 10(6) M-1.s-1 in the presence of the
      kringles 1-3 domain of bovine plasmin. In contrast to this, substantial
      reductions of k+1 were seen in the presence of concentrations of 6-amino-hexanoic
      acid corresponding to lysine-binding-site interactions and far too low to be
      attributed to active-site interactions with the bovine plasmins (for each, Ki =
      42 mM). All in all, the data indicated that the lysine-binding site(s) not of
      kringle 1, but of midiplasmin (those of kringles 4 and 5) are regulating the
      inhibition reaction.

PMID- 7530002
TI  - Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction
      of nitric oxide synthase in activated macrophages.
AB  - L-Arginine-derived nitric oxide (NO) and its derivatives, such as peroxynitrite
      and nitrogen dioxide, play a role in inflammation and also possibly in the
      multistage process of carcinogenesis. We investigated the effect of various non
      steroidal anti-inflammatory agents and related compounds on the induction of NO
      synthase (NOS) in RAW 264.7 macrophages activated with lipopolysaccharide (LPS)
      and interferon-gamma (IFN-gamma). Low concentrations of curcumin, a potent anti
      tumour agent having anti-inflammatory and anti-oxidant properties, inhibited NO
      production, as measured by the amount of nitrite released into the culture medium
      in 24 h (IC50 = 6 microM). NOS activity in soluble extracts of macrophages
      activated for 6-24 h in the presence of curcumin (10 microM) was significantly
      lower than that of macrophages activated without curcumin. Northern-blot and
      immunoblotting analyses demonstrated that significantly reduced levels of the
      mRNA and 130-kDa protein of inducible NOS were expressed in macrophages activated
      with curcumin, compared to those without curcumin. Inhibition of NOS induction
      was maximal when curcumin was added together with LPS and IFN-gamma and decreased
      progressively as the interval between curcumin and LPS/IFN-gamma was increased to
      18 h.

PMID- 7530000
TI  - pp60c-src expression in rat spermatogenesis.
AB  - A fractionation of the membrane extract of rat testes revealed the existence of
      pp60c-src kinase activity. The expression of pp60c-src was examined in the
      developing rat testes. The immunecomplex kinase assay using a monoclonal antibody
      specific to pp60c-src (mAb327) showed that the expression of pp60c-src kinase
      activity increased during the development of rat testes and declined in the
      adult. The increase in pp60c-src kinase activity observed during the development
      of rat testes was accompanied with an increase in the amount of pp60c-src
      protein. The peak period in the increase of pp60c-src kinase activity well
      coincided with the timing, when the spermatogenesis by meiosis just began. The
      immunohistochemical staining of pp60c-src in rat testes demonstrated that pp60c
      src is most abundantly expressed in the spermatids which are the spermatogenic
      cells in the post-meiotic phase of the spermatogenesis. These findings strongly
      suggest that pp60c-src is a developmentally regulated gene product which is
      involved in rat spermatogenesis.

PMID- 7530001
TI  - Functional expression of three isoforms of human nitric oxide synthase in
      baculovirus-infected insect cells.
AB  - Complementary DNAs encoding three human isoforms (neuronal, inducible, and
      endothelial) of nitric oxide synthase were cloned into the baculovirus expression
      vector pVL1392/1393. Transfection of Sf-9 insect cells with the recombinant
      baculovirus resulted in the expression of high levels of nitric oxide synthases.
      The expressed proteins of neuronal and inducible nitric oxide synthase were
      predominantly soluble, whereas the endothelial enzyme was for the most part,
      particulate. Recombinant enzymes were purified with 2',5'-ADP Sepharose affinity
      chromatography. The effects of reference enzymatic inhibitors (NG-methyl-L
      arginine, NG-nitro-L-arginine and N-iminoethyl-L-ornithine) on recombinant
      expressed proteins were not significantly different from native nitric oxide
      synthase enzyme preparations. L-aminoguanidine was found to be much less potent
      in inhibiting recombinant or native human inducible nitric oxide synthase
      compared to the murine isoform. These findings indicate previously unappreciated
      interspecies differences in the action of nitric oxide synthase enzymatic
      inhibitors. The functional expression of human nitric oxide synthase isoforms in
      a heterologous expression system allowed screening of novel inhibitors. Studies
      indicated that S-ethylisothiourea and 2-amino-5,6-dihydro-6-methyl-4H-1,3
      thiazine were potent novel inhibitors of human nitric oxide synthases.

PMID- 7530003
TI  - Jararhagin and jaracetin: novel snake venom inhibitors of the integrin collagen
      receptor, alpha 2 beta 1.
AB  - Two novel proteins, jararhagin and jaracetin, were purified from Bothrops
      jararaca viper venom. Jararhagin is a 55-kDa member of the metalloprotease
      disintegrin family. Jaracetin is a 60-kDa dimer representing a differently
      processed form of jararhagin. Like botrocetin, a previously described viper venom
      protein, jararhagin and jaracetin modulated binding of von Willebrand Factor to
      the glycoprotein Ib-IX complex on platelets through a specific interaction with
      the von Willebrand Factor A1 domain. Both jararhagin and jaracetin, but not
      botrocetin, also blocked alpha 2 beta 1-dependent platelet adhesion to collagen,
      a receptor interaction mediated through a homologous A domain on the integrin
      alpha 2 subunit.

PMID- 7530005
TI  - The identification of the pterin-binding domain in the nitric oxide synthase's
      sequence.
AB  - Comparative studies of primary sequences of nitric oxide synthase (NOS) and
      pterin-dependent enzymes has shown that the biopterin-dependent site of NOS is
      localized between the regions responsible for calmodulin and FMN binding. On the
      example of NOS from rat brain it was demonstrated that this biopterin-binding
      site is located in the region 750-769. Pairwise alignment of amino acids
      sequences of NOS from rat brain and rat xantine dehydrogenase revealed that the
      two proteins are 39.7% identical.

PMID- 7530004
TI  - Arginase induction by suppressors of nitric oxide synthesis (IL-4, IL-10 and
      PGE2) in murine bone-marrow-derived macrophages.
AB  - The present study addresses the regulatory mechanisms involved in the arginine
      metabolism of macrophages by arginase and nitric oxide synthase. Induction of
      both enzymes with LPS or by mixed lymphocyte reaction has been reported. Here, we
      demonstrate that these enzymes can be independently induced in murine bone-marrow
      derived macrophages with the appropriate agonists. Arginase expression is
      specifically triggered by IL-4, IL-10, PGE2 as well as non-toxic or detoxified
      LPS. Conversely, IFN gamma induces only NO synthesis in these cells. The results
      demonstrate that the metabolism of arginine in macrophages is controlled by
      TH1/TH2-dependent cytokines and suggest a regulatory role of arginase on the NO
      synthesis by intracellular substrate depletion.

PMID- 7530006
TI  - [Study of the transmembrane organization of the C-terminal domain of the alpha
      subunit of Na+,K+-ATPase using polyclonal antibodies to its perimembrane
      fragments].
AB  - The fragments 825-842, 868-886, 928-945, 946-967, 962-978 of the alpha-subunit of
      the porcine Na+,K(+)-ATPase were expressed in E. coli as fusion proteins with
      human tumour necrosis factor. Polyclonal antibodies were obtained to these
      fragments. The location of the chosen fragments according to the plasma membrane
      was determined with the polyclonal antibodies by ELISA on intact, lysed or
      solubilized pig kidney embryo cells. The fragments 825-842, 928-945, and 962-978
      contained intracellular epitopes and did not contain extracellular ones; the
      fragments 868-886 and 946-967 did not contain any exposed epitopes.

PMID- 7530008
TI  - [Isolation and characteristics of an ordered library of transcribed sequences of
      human chromosome 19 from hybrid human-hamster cells].
AB  - A new technique based on Alu-PCR amplification of hn-RNA is described for the
      extraction of human-specific transcribed sequences from a hybrid cell line.
      Arrayed library of hn-cDNA was constructed and characterized by sequencing about
      80 individual clones. A high enrichment by human-specific sequences (about 95%)
      was demonstrated.

PMID- 7530007
TI  - [Study of the structural organization of OSCP--subunits of H+-ATPase of porcine
      heart mitochondria].
AB  - Unmodified and citraconilated OSCP of the pig heart mitochondrial H(+)-ATPase
      were hydrolysed by proteinase from Staphylococcus aureus V8 and trypsin,
      respectively. To purify the individual peptides, various types of HPLC and
      covalent chromatography on SH-Sepharose were used. By the automatic Edman method
      complete or partial amino acid sequences of the peptides obtained were
      determined, thus allowing for the reconstruction of the primary structure of pig
      OSCP. A linear antigenic determinant recognizable by A1 monoclonal antibody
      against bovine OSCP, was localized. Studies showed Gly43 residue (bovine OSCP) to
      be replaced by Ala43 (pig OSCP), which is responsible for a decrease of the
      affinity of the monoclonal antibody A1 to pig OSCP. Comparative analysis of
      primary structures of bovine and pig OSCP was carried out.

PMID- 7530009
TI  - [Antigenic bacterial polysaccharides. Structure of O-specific polysaccharides
      from Pseudomonas cepacia serogroups C, I, O1, and O4].
AB  - Like some Pseudomonas cepacia serogroups studied earlier, serogroups C, I
      (Nakamura), O1 and O4 (Heidt) are characterized by the presence of at least two
      structurally different O-antigenic polysaccharide chains in cell-wall
      lipopolysaccharides. On the basis of acid hydrolysis, methylation, 1H- and 13C
      NMR spectroscopy, including computer-assisted 13C-NMR-based analysis, the
      complete structures of the predominant polysaccharides of serogroups I (I), C and
      O4 (III) and the minor polysaccharides of serogroups I (II) and O1 (V) were
      established, and the structure of the predominant polysaccharide of serogroup O1
      (IV) established earlier (Cox A. D., Wilkinson S. G.@Carbohydr. Res. 1990. V.
      195. No 2. P. 295-301) was confirmed.

PMID- 7530011
TI  - Analysis of anatomical sites at which galanin impairs delayed nonmatching to
      sample in rats.
AB  - Galanin, a neuropeptide that coexists with acetylcholine in the septohippocampal
      pathway of the rat, impairs operant delayed nonmatching to sample (DNMTS) when
      administered intracerebroventricularly. Microinjection experiments were conducted
      to determine the anatomical site or sites at which galanin acts to disrupt DNMTS.
      Galanin (0.1, 0.4, or 1.6 nmol) was microinjected into the ventral hippocampus,
      amygdala, nucleus basalis magnocellularis, prefrontal cortex, or entorhinal
      cortex. Galanin disrupted DNMTS in a dose-dependent manner when microinjected
      into the ventral hippocampus but not at the other sites tested. These findings
      are consistent with the ability of galanin to inhibit physiological and
      biochemical actions of acetylcholine in the ventral hippocampus.

PMID- 7530012
TI  - Direct analysis of tumor-associated peptide antigens.
AB  - Adoptive immunotherapy with tumor-specific cytotoxic T lymphocytes (CTLs) can
      induce tumor regressions in animals and in human cancer patients. Antigens
      recognized by CTLs from cancer patients are being sought as possible immunogens,
      a number of which have been identified during the past year. The ultimate result
      may be the development of novel peptide-based immunotherapies and a new
      understanding of the T-cell response to human cancer.

PMID- 7530013
TI  - Blockade of the CD28 co-stimulatory pathway: a means to induce tolerance.
AB  - Presentation of antigen to the T-cell receptor (TCR) without co-stimulation
      results in a state of antigen-specific unresponsiveness on rechallenge, known as
      anergy in vitro and tolerance in vivo. Mounting evidence suggests that inhibition
      of the B7-CD28 co-stimulatory pathway is both necessary and sufficient to induce
      antigen-specific T-cell anergy. Anergy is not static because specific signals are
      required to maintain this state and prevent its reversal. Attention to these
      issues will be critical to translate these basic studies to the clinical arenas
      of transplantation, tumor immunity and autoimmunity.

PMID- 7530014
TI  - Dialyzer permeability for low-molecular-weight proteins. Comparison between
      polysulfone, polyamide and cuprammonium-rayon dialyzers.
AB  - The aim of the study was to compare under in vivo conditions the new polyamide
      (Polyflux 160, Gambro) and cuprammonium-rayon dialyzers (AM-FP-17, Asahi; Clirans
      SE15NL, Terumo) with the polysulfone dialyzer (F60, Fresenius) regarding their
      permeability for beta-2-microglobulin (11.8 kD), retinol binding protein (21 kD),
      alpha-1-microglobulin (26.7 kD), alpha-1-glycoprotein (41 kD), alpha-1
      antitrypsin (54 kD), albumin (66.3 kD) and transferrin (90 kD). The marker
      substances were measured by nephelometry or radioimmunoassay. To evaluate the
      membrane permeability, sieving coefficients 20 min after the start of
      hemodialysis were calculated using the concentration in the afferent and efferent
      blood line and in the ultrafiltrate. To get an idea about convective protein loss
      during a hemofiltration session, the values were computed in milligrams per 20
      liters ultrafiltrate. Concerning the permeability of beta-2-microglobulin, the
      F60, AM-FP-17 and the Polyflux 160 hemofilter were comparable. In the molecular
      weight range of 20-60 kD both synthetic hemofilters were nearly impermeable.
      However, the cuprammonium-rayon dialyzers showed in this range a higher cutoff.
      The calculated albumin and transferrin loss is lower than those of CAPD patients
      or patients with nephrotic syndrome.

PMID- 7530015
TI  - Bacteria-specific cytotoxic CD8+ T cells: a missing link in the pathogenesis of
      the HLA-B27-associated spondylarthropathies.
AB  - The term seronegative spondylarthropathies is used for an entity of rheumatic
      syndromes of peripheral joints and the spine (ankylosing spondylitis, reactive
      arthritis, Reiter's syndrome, arthritis in psoriasis and in inflammatory bowel
      disease) which are strongly associated with the MHC class I molecule HLA-B27.
      However, the mechanisms whereby HLA-B27 confers disease susceptibility have so
      far remained unknown. There is strong evidence that gut inflammation and
      infection with gram-negative bacteria play a role in the induction of B27
      associated disease. HLA-B27, like other MHC class I molecules, physiologically
      binds antigenic peptides in its binding groove and presents them to CD8+ T
      lymphocytes. Consequently, if the disease association with HLA-B27 arises from
      its role as a T-cell restriction element, synovial fluid CD8+ rather than CD4+ T
      cells should play a prominent pathogenetic role and should be detectable within
      the affected joints. In this paper, recent studies on bacteria-specific cytotoxic
      T cells and on peptide binding to HLA-B27 are reviewed. Particular emphasis is
      laid on the role of HLA-B27 restricted synovial CD8+ T cells with specificity for
      bacterial antigens or autoantigens. These cytotoxic T cells could provide a
      missing link in the pathogenesis of the spondylarthropathies and could now serve
      as tools to identify the critical antigenic epitopes of bacterial and self
      peptides which are involved in disease induction.

PMID- 7530010
TI  - Pyrroloquinolinone methylderivatives, furocoumarin analogues: synthesis and
      biological activity.
AB  - Searching new photochemotherapeutic agents, a series of methylpirroloquinolinones
      were prepared by a new synthetic pathway, thus univocally obtaining the title
      compounds. The photobiological activity of some of these compounds was assayed;
      upon UVA activation, a marked capacity of inhibiting macromolecular synthesis in
      Ehrlich cells was observed, which appeared to be markedly high testing protein
      synthesis. Pyrroloquinolinones induced a strong inhibition of the clonal growing
      capacity of HeLa cells cultivated in vitro. Studying DNA photodamage in HL60
      cells high amounts of single strand breaks and DNA-protein cross-links were
      detected. Pyrroloquinolines inhibited T2 bacteriophage infectivity, but induced
      no significant amounts of revertants in E. coli WP2 TM9, a strain very sensitive
      to DNA damage. On the contrary, 8-MOP, tested in the same experimental conditions
      exhibited an evident photomutagenecity. These data suggest that pyrroloquinolines
      induced antiproliferative effects by a mechanism in which DNA-photobinding
      practically does not takes place, and therefore different from that shown by
      known furocoumarins. Pyrroloquinolinones showed also a moderate antiproliferative
      activity in the dark.

PMID- 7530016
TI  - Role of interferons in the regulation of cell proliferation, differentiation, and
      development.
AB  - There now appears to be evidence to support the view that the type I IFNs are
      naturally produced negative regulators of growth that also modify cell
      differentiation. Consistent with this, it appears that the ability to produce and
      respond to IFN is suppressed in early embryonic development when cell
      proliferation and differentiation are essential. In the later stages of fetal
      development, IFN production is de-repressed, and cells show increased sensitivity
      to IFN, which may be important in regulating cell proliferation and/or
      differentiation processes or the interaction between fetal and maternal tissues.
      Interestingly, the IFN system can also be suppressed in disease states such as
      the development of tumours or in the establishment of a (chronic) viral
      infection. Therefore, understanding the developmental regulation of the IFN
      system may be important to understanding and controlling the IFN system in
      disease. More extensive studies of the developmental stage and tissue-specific
      expression of type I IFNs and their receptors are necessary, as well as more
      direct in vivo experiments to further elucidate the role of the IFN system in
      reproduction and development.

PMID- 7530017
TI  - Differential expression of ARIA isoforms in the rat brain.
AB  - ARIA, heregulin, neu differentiation factor, and glial growth factor are members
      of a new family of growth and differentiation factors whose effects have been
      assayed on Schwann cells, skeletal muscle cells, and mammary tumor cell lines. To
      gain insight into their roles in the CNS, we studied the expression of ARIA in
      the rat brain. We found ARIA mRNA in all cholinergic neurons throughout the CNS,
      including motor neurons and cells of the medial septal nucleus and the nucleus
      basalis of Meynert. We also found that ARIA induces tyrosine phosphorylation of a
      185 kDa protein in central and peripheral targets of these cholinergic neurons.
      ARIA mRNA, however, is not restricted to cholinergic neurons, suggesting that it
      may also play a role at other types of synapses. Its distribution in germinal
      layers of the telencephalon and cerebellum suggests that it may also play a role
      in the proliferation and/or migration of neuronal and glial precursor cells.

PMID- 7530018
TI  - Calcium release from the nucleus by InsP3 receptor channels.
AB  - The nucleus is surrounded by a double membrane separating it from the cytoplasm.
      The perinuclear space is continuous with endoplasmic reticulum, and the nuclear
      outer membrane shares many features with the reticular membrane. We now show that
      inositol 1,4,5-trisphosphate (InsP3) receptors associated with the nucleus
      release Ca2+ from isolated Xenopus laevis oocyte nuclei. Electrophysiological
      measurements of the intracellular InsP3 receptor in its native membrane have not
      been possible on the fine filamentous endoplasmic reticulum. In this paper, we
      directly measure InsP3-dependent receptor channels in isolated nuclei. The
      nuclear InsP3 receptor is activated by InsP3 and modulated by Ca2+. The channel
      is weakly regulated by ATP, is mildly voltage dependent, and has a greater
      conductance with monovalent cations than with divalent cations.

PMID- 7530019
TI  - A histidine residue associated with the gate of the cyclic nucleotide-activated
      channels in rod photoreceptors.
AB  - Ion channels directly activated by the binding of cGMP mediate the electrical
      response to light in rod photoreceptors. Here, we identify a region of the
      channel associated with the activation gate using potentiation by intracellular
      Ni2+. Low concentrations of Ni2+ caused a dramatic increase in the response of
      rod channels expressed in Xenopus oocytes to both cGMP and cAMP. Whereas
      saturating cAMP normally activated less than 1% of the channels, Ni2+ increased
      the cAMP potency nearly 50-fold. Ni2+ did not produce potentiation in the related
      channel from the olfactory epithelium. We localized the Ni(2+)-binding site to a
      histidine residue in the putative intracellular mouth of the rod channel (H420).
      We propose a mechanism for potentiation in which Ni2+ binds to H420 primarily
      when the channel is open, stabilizing the open conformation. These experiments
      suggest that H420 is associated with the activation gate.

PMID- 7530020
TI  - Buried surface analysis of HIV-1 reverse transcriptase p66/p51 heterodimer and
      its interaction with dsDNA template/primer.
AB  - The p66/p51 human immunodeficiency virus type 1 reverse transcriptase is a
      heterodimer with identical N-terminal amino acid sequences. The enzyme contains
      two polymerization domains and one RNase H domain, which is located at the C
      terminus of the p66 subunit. Both polymerization domains fold into four
      individual subdomains that are not arranged in a similar fashion, forming an
      unusually asymmetric dimer. The complexity of the RT p66/p51 heterodimer
      structure is simplified using solvent-accessibility surface areas to describe the
      buried surface area of contact among the different subdomains. In addition, the
      RT/DNA contacts in the recently published RT/DNA/Fab structure [Jacobo-Molina et
      al., Proc. Natl Acad. Sci. USA, 90, 6320-6324 (1993)] are described using the
      same approach. Finally, the RT/DNA complex is compared with other dimeric DNA
      binding proteins. It was found that the size of the protein and the extent of the
      dimer interface were not directly related to the extent of contact between the
      protein and the DNA. Furthermore, RT, the only protein that is not a sequence
      specific DNA binding protein in this analysis, had the largest surface of
      interaction with the nucleic acid.

PMID- 7530022
TI  - Current perspectives on particulate induced pulmonary tumours.
AB  - 1. Chronic exposure to insoluble particulates can lead to the development of
      pulmonary tumours. These have been classified as broncho-alveolar or
      squamous/epidermoid according to their histopathological characteristics and have
      been reported in inhalation studies in rats of materials ranging from diesel
      exhaust and silica to titanium dioxide. 2. The sequence of changes within the rat
      lung leading to tumours has been characterised. It is apparent that one
      prerequisite is that the lung load of the particulate matter must exceed the
      normal clearance capacity, either by overloading the normal alveolar macrophage
      mediated mechanism or by induction of toxicity with materials such as silica.
      This results in inflammatory responses, including, or resulting in, epithelial
      hypertrophy and/or hyperplasia and squamous metaplasia. The persistence of these
      tissue responses over chronic time periods can lead to tumorigenesis. 3. Research
      into the mechanisms involved in the initiation and progression of both the
      inflammatory response and subsequent tumorigenic response to lung particulate
      loading is in progress. Impairment of macrophage function and mobility by inert
      particles constitutes one route by which this can arise, as does toxicity to this
      cell type by biologically reactive particles. At the molecular level, the role of
      inflammatory mediators, especially the cytokines, has received much attention. 4.
      Particulate induced lung tumours are perceived to be a phenomenon specific to the
      rat and their relevance to man is questionable.

PMID- 7530023
TI  - Influence of deletions in N or C terminus of HIV-1 glycoprotein 120 on binding of
      infectivity-enhancing antibody.
AB  - Human monoclonal antibody 2.3a was previously shown to enhance human
      immunodeficiency virus type 1 (HIV-1) infection in vitro. This enhancing antibody
      recognizes a conserved epitope of envelope glycoprotein gp120. We report here
      that binding of the 2.3a antibody to gp120 is significantly affected by deletions
      of certain N- or C-terminal residues of gp120. However, not all such deletions
      affect the epitope recognized by a broadly neutralizing human monoclonal
      antibody, 1.5e. These findings suggest the feasibility of designing a gp120
      antigen that is free of 2.3a epitope while retaining the conformation of the 1.5e
      epitope.

PMID- 7530021
TI  - Pulmonary alveolar phospholipoproteinosis induced by Orasol Navy Blue dust.
AB  - 1. Orasol Navy Blue (ONB) is a water-insoluble nitroaromatic dye to which workers
      may be exposed to the dust. 2. Rats and guinea pigs exposed for 30 min to 173 mg
      m-3 did not show toxic signs or respiratory tract histopathology. 3. Rats, mice
      and guinea pigs were exposed 6 h a day for 20 or 100 days to 2.05 mg m-3 ONB dust
      (particle size, 33.6% < 5 microns). Except for decreased body weight of guinea
      pigs during the exposure period, no adverse signs were seen over a 1-year period
      from the first exposure. Respiratory tract histopathology was not seen in mice or
      guinea pigs. Rats showed scattered alveolar lesions characterized by aggregations
      of macrophages, PAS-positive debris, cholesterol, sudanophilia and birefringence,
      with preservation of the interstitum and no fibrogenic response. The number and
      size of these lesions was related to the duration of exposure. 4. The similarity
      of the lesions seen in the rat following exposure to ONB dust and those seen in
      humans from other exogenous causes of pulmonary alveolar phospholipoproteinosis
      suggests that overexposure of humans to a respirable dust of ONB may produce this
      lesion. 5. The rat is a convenient model to investigate pulmonary alveolar
      phospholipoproteinosis by exposure to respirable dusts.

PMID- 7530025
TI  - Analysis of HIV type 1 reverse transcriptase expression in a human cell line.
AB  - The functional analysis of human immunodeficiency virus type-1 (HIV-1) reverse
      transcriptase (RT) subunits on transient and constitutive expression, in the
      absence or presence of the HIV-1 protease (PR) expression, in a human cell line
      is described. HIV-1 RT is a heterodimer composed of a 51-kDa subunit (p51) and a
      66-kDa subunit (p66). Cloning and expression of the RT region of the HIV-1 pol
      gene in the HT-1080 human fibrosarcoma cell line yielded p66 without any
      detectable p51 and a low level of RT activity could be measured. Transient
      expression of PR and RT in cis generated p51 and p66, but when RT and PR were
      expressed in trans only p66 was produced. Attempts to establish a stable cell
      line expressing the PR-RT region of the pol gene were hampered by an apparent
      intolerance of HT-1080 cells to the HIV-1 PR expression. Therefore, to generate
      p51 independent of PR expression, the 51-kDa subunit was cloned separately. p51
      lacked detectable RT activity. Coexpression of p51 and p66 resulted in a dramatic
      increase in RT activity. Stable HT-1080 cells producing both p51 and p66
      exhibited on average a 15-fold increase in RT activity compared to the parental
      cell line. Immunofluorescence revealed a diffuse cytoplasmic localization of p51
      and p66. To date, this is the first example of a human cell line that is
      constitutively expressing HIV-1 RT in the absence of HIV-1 infection.

PMID- 7530027
TI  - [The expression of granulocyte colony-stimulating factor in malignant gliomas].
AB  - In this study, we investigated the expression of granulocyte colony-stimulating
      factor (G-CSF), G-CSF mRNA, G-CSF receptor mRNA in glioma cell lines, G-CSF in
      glioma cyst fluids, and the effect of recombinant G-CSF on the proliferation of
      glioma cells. First, to determine whether G-CSF is produced by glioma cells, we
      analyzed for the presence of G-CSF by ELISA in supernatants from glioma cell
      lines. G-CSF was detected in six of fourteen glioma cell lines constitutively,
      and, after stimulation with tumor necrosis factor-alpha (TNF-alpha), G-CSF was
      detected in four of eight cell lines which did not produce G-CSF constitutively.
      Then, we analyzed the expression of G-CSF mRNA by reverse-transcriptase
      polymerase chain reaction (RT-PCR) in six cell line, of which two produced G-CSF
      constitutively and three produced G-CSF only after stimulation with TNF-alpha. G
      CSF mRNA was detected in all cell lines studied. To determine whether G-CSF was
      produced in vivo, we analyzed the presence of G-CSF by ELISA in five glioma cyst
      fluids, but G-CSF was not detected in any. We also analyzed the effect of G-CSF
      on the proliferation of glioma cells. The growth of glioma cells alone was not
      different from that of glioma cells incubated with recombinant G-CSF. In
      addition, we analyzed the presence of G-CSF receptor mRNA in glioma cells by RT
      PCR; G-CSF receptor mRNA was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530026
TI  - Perinatal transmission of HIV type 1: associations with maternal anti-HIV
      serological reactivity. Mothers and Infants Cohort Study and the HIV-1 Perinatal
      Serology Working Group.
AB  - As a hypothesis-generating study of large regions of the human immunodeficiency
      virus type 1 (HIV-1) envelope, we collaborated with several laboratories to test
      sera from subgroups of 65 HIV-1-positive pregnant women, 18 (28%) of whom
      transmitted the virus to their infants. Assays included neutralizing antibodies
      to HIVLAI and reactivity to 102 HIV-1 Env peptides with sequences based on
      strains LAI, MN, SC, RF, and WMJ-2 as well as several clinical isolates, spanning
      about 65% of gp120 and about 80% of gp41. Results for the V3 loop and for
      neutralizing activity were conflicting and for the most part did not reach
      statistical significance. Transmission risk appeared lower with reactivity to a
      few gp41 epitopes (amino acids 571-585, 736-750, and perhaps 650-663), whereas
      risk appeared higher with reactivity to two gp120 epitopes (amino acids 466-480
      and 475-486) and one gp41 epitope (amino acids 547-576). However, these
      associations could have occurred simply by chance because such a large number of
      peptides was tested. With independently synthesized peptides, results between
      laboratories often were inconsistent. However, reproducibility was good (rank
      correlation coefficient > or = 0.78) when the same protocols and peptides were
      used. Although this study could not identify a humoral immune response to linear
      Env peptides that consistently and broadly protected against perinatal
      transmission of HIV-1, there were regions of gp120 and gp41 that should be
      evaluated in larger cohorts and with techniques to investigate potential
      conformational epitopes and neutralization to autologous or clinical isolates of
      HIV-1 from the community.

PMID- 7530024
TI  - Monoclonal antibodies against HIV type 1 integrase: clues to molecular structure.
AB  - Eleven murine hybridoma clones were selected for their ability to produce anti
      HIV-1 integrase (IN) antibodies. Competition and epitope mapping studies allowed
      segregation of the monoclonal antibodies (MAbs) into four distinct classes. The
      five MAbs that comprise the first class showed high affinity for epitopes within
      an N-terminal domain of 58 amino acids that includes a conserved zinc finger
      motif. The second class, with two MAbs, showed high affinity for epitopes within
      29 amino acids at the C terminus. Another two MAbs, which constitute the third
      class, displayed moderate affinities for epitopes that mapped to regions within
      the highly conserved catalytic core referred to as the D,D(35)E domain. One of
      these MAbs showed significant cross-reactivity with HIV-2 IN and weak, but
      detectable, cross-reactivity with RSV IN. The remaining two MAbs, which comprise
      the fourth class, exhibited fairly low binding affinities and appeared to
      recognize epitopes in the zinc finger motif domain as well as the C-terminal half
      of the IN protein. The MAbs can be used for immunoprecipitation and
      immunoblotting procedures as well as for purification of HIV-1 IN protein by
      affinity chromatography. We show that several can also be used to immunostain
      viral IN sequences in HIV-1-infected T cells, presumably as a component of Gag
      Pol precursors. Finally, analysis of our mapping and competition data suggests a
      structure for mature IN in which the C terminus approaches the central core
      domain, and the N and C termini touch or are proximal to each other. These MAbs
      should prove useful for further analyses of the structure and function of IN both
      in vitro and in vivo.

PMID- 7530028
TI  - Effects of preoperative methoxamine on blood loss and haemodynamic variables
      during transurethral prostatic resection under spinal anaesthesia.
AB  - Thirty-six patients who presented for transurethral prostatic resection were
      allocated randomly to one of two groups. Patients in group A were given
      methoxamine 10 mg i.m., 15 min before spinal anaesthesia. Patients in group B
      acted as a control group. All patients received spinal anaesthesia. Preoperative
      administration of methoxamine 10 mg i.m. decreased blood loss significantly and
      improved haemodynamic stability compared with the control group.

PMID- 7530029
TI  - Influence of different anticoagulation regimens on platelet function during
      cardiac surgery.
AB  - Qualitative platelet defects are of great importance as a cause of bleeding in
      cardiac surgery. We have studied the effects of different anticoagulation
      regimens on platelet function in 60 patients undergoing elective aorto-coronary
      bypass grafting with cardiopulmonary bypass (CPB). Patients were allocated
      randomly to four groups (each group n = 15) to receive either: bovine heparin 300
      u. kg-1 (standard); heparin 300 u. kg-1 followed by a continuous infusion of
      10,000 u. kg-1 until the end of CPB; heparin 600 u. kg-1; or heparin 600 u. kg-1
      in addition to high-dose aprotinin 2 million iu before CPB, 500,000 iu h-1 until
      the end of operation and 2 million iu added to the prime. Platelet function was
      evaluated by aggregometry (turbidometric technique) using adenosine triphosphate
      (ADP) 2.0 mumol litre-1, collagen 4 microliters ml-1, adrenaline 25 mumol litre-1
      and saline solution (control) as inducers. Both maximum aggregation and maximum
      gradient of aggregation were measured in arterial blood samples before, during
      and after CPB until the first day after operation. Mean total dose of heparin
      given in groups 2, 3 and 4 was more than 50,000 u. and differed significantly
      from that of group 1 (28,150 (SD 4700)u.). Platelet aggregation variables were
      most depressed during CPB and until the end of surgery in groups 2 and 3 (maximum
      aggregation - 54% to - 75% of baseline values). In the postoperative period,
      platelet function recovered but did not completely reach baseline values in these
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530030
TI  - Hematologic phenotype of the mutations IVS1-n6 (T-->C), IVS1-n110 (G-->A), and
      CD39 (C-->T) in carriers of beta-thalassemia in Greece.
AB  - The hematologic phenotype was characterized in heterozygotes for three of the
      most common beta-thalassemia mutations in the Greek population. The study
      included 17 carriers of beta++ IVS1-n6 (T-->C), 21 carriers of beta+ IVS1-n110 (G
      ->A), and 17 carriers of beta 0 CD39 (C-->T). The 55 beta-thalassemia
      heterozygotes were selected from among parents of patients on regular transfusion
      regimens, and the beta-thalassemia mutation was identified by means of the
      polymerase chain reaction to amplify the appropriate region of the beta-globin
      gene and then by allele-specific oligonucleotide hybridization. The assessment of
      hematologic phenotype included complete blood count and quantitation of
      hemoglobin HbA2 and HbF and of the globin chain biosynthesis ratio. Comparison
      and statistical analysis of the hematologic parameters for the three mutations
      demonstrated no consistent correlation among the three mutations relative to Hb
      levels, hematocrit, and red cell indices, although heterozygotes for the IVS1-n6
      mutation produce red blood cells with slightly higher mean corpuscular volume;
      significantly lower values of HbA2 (mean, 3.81% +/- 0.62% with four values less
      than 3.60%) in IVS1-n6 heterozygotes compared with IVS1-n110 heterozygotes (mean,
      4.69% +/- 0.48%) and CD39 heterozygotes (mean, 4.75% +/- 0.50%, P < 0.001); and
      significantly higher HbF levels in CD39 heterozygotes (mean, 2.31% +/- 1.52%)
      compared with IVS1-n6 heterozygotes (mean, 0.79% +/- 0.45%, P < 0.01) and IVS1
      n110 heterozygotes (mean, 1.17% +/- 0.75%, P < 0.01). With respect to the HbA2
      levels, the findings are in agreement with previous studies in Mediterranean
      populations; the slightly higher levels of HbF in CD39 heterozygotes appear to be
      reported for the first time.

PMID- 7530031
TI  - Wilms' tumor with intracardiac extension: chemotherapy before surgery.
AB  - The article describes two Chinese boys ages 2 and 3 years with unilateral Wilms'
      tumors complicated by intracaval and intracardiac extension. In contrast to the
      previously recommended treatment with surgery followed by chemotherapy and
      radiation therapy, the children were managed primarily with combination
      chemotherapy before definitive operation. Reduction of tumor size on serial
      imaging was documented, and no viable tumor cells were found when the involved
      kidney and right atrium were explored. Both patients remained alive without
      evidence of disease more than 5 years after initial diagnosis. A literature
      search revealed case reports and retrospective analyses of 70 patients with
      Wilms' tumors and intracardiac involvement, and a tendency toward preoperative
      chemotherapy with or without the addition of radiation therapy was observed. The
      overall outcome of this group of patients parallels the outcome of those without
      intracardiac extension by histology and stage. Wilms' tumor presenting with
      extension into the inferior vena cava and right atrium is thus rare and renders
      the affected child with additional cardiovascular complications and operative
      risks. As a result of the uncommon occurrence, a consensus on management based on
      prospective study would be difficult. The present report and the literature are
      supportive of the use of preoperative chemotherapy in the initial management of
      advanced Wilms' tumor extending into the right atrium.

PMID- 7530032
TI  - Successful treatment of a mediastinal endodermal sinus tumor in a 2-year-old
      child.
AB  - The article describes a primary mediastinal endodermal sinus tumor in a child.
      The employment of multidrug therapy combined with surgical treatment resulted in
      a long-term remission in this rare tumor.

PMID- 7530034
TI  - Dose intensity in breast cancer chemotherapy--the way ahead?

PMID- 7530033
TI  - [Structural and functional relationships demonstrated by the study of V3 loop
      heterogeneity].
AB  - Data obtained from genomic sequence analysis of the gp 120 V3 loop show that some
      of the phenotype features depend on the modifications produced in the amino acid
      sequence of this region. Phenotypical characterization of HIV isolates is based
      on their sensitivity to neutralizing antibodies, the appearance of virus variants
      showing unusual tropism, higher cytopathogenicity in vitro and modified virulence
      in vivo, etc. Sequencing data published since now concern strains from the Euro
      American area only, the other geographical areas being neglected. So, these
      informations support some relations between structure and function, but don't
      allow a prediction about the evolutive capacity of HIV strains, the distinction
      between conserved and variable regions nor the understanding of medical
      signification of some specific genomic changes. Three aspects important for
      clinical evolution of the disease are discussed in detail: genomic changes in V3
      encoding sequence associated with virulence, changes associated with neurotropism
      for macrophages, changes conditioning sensitivity to neutralizing antibodies.

PMID- 7530035
TI  - The endodermal sinus tumour and clear cell ovarian cancer.
AB  - There are similarities between clear cell epithelial ovarian carcinoma and
      endodermal sinus tumours. Apart from the morphological and clinical
      characteristics there are immunohistochemical markers of value in differentiating
      these 2 tumours and the detection of a raised serum AFP is characteristic of
      endodermal sinus tumours. These 3 cases we describe show the fallibility of the
      classical differentiating criteria between these two tumours.

PMID- 7530036
TI  - Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in
      AIDS.
AB  - The objective of this study was to assess the efficacy and toxicity of a novel
      Stealth liposomal encapsulated formulation of doxorubicin (Doxil). A Phase I/II
      dose escalation study was carried out in a specialist HIV oncology unit in a
      teaching hospital (predominantly in an outpatient department). Fifteen patients
      with HIV related, biopsy confirmed, cutaneous Kaposi's sarcoma, with or without
      visceral involvement of sufficient severity to require systemic chemotherapy,
      were treated. Most patients had poor prognosis disease as assessed by the
      Tumour/Immune status/Systemic symptoms (TIS) system and Karnofsky indices; six
      patients had previously received combination chemotherapy. Primary treatment
      consisted of a dose of Doxil 10 mg/m2, repeated after 2 weeks. If the Kaposi's
      sarcoma (KS) responded and the treatment was tolerated, the patient began
      maintenance therapy at the same dose every 2 weeks. If there was no clinical
      response, the dose was increased to 20 mg/m2 for the further two cycles, before
      proceeding to maintenance therapy. Treatment continued until other intercurrent
      disease, lack of further response, patient preference, or toxicity precluded
      further treatment. Tumour response was assessed 2 weeks after completion of at
      least two cycles of chemotherapy. Toxicity was assessed for each cycle. Doxil was
      well tolerated, and toxicity was manageable, the principal toxicity being
      haematological. A partial response rate of 11/15 (73%) was achieved, with disease
      stabilization in the remaining patients. We conclude that Doxil is an effective
      palliative treatment for epidemic KS in a patient group with a poor predicted
      outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530037
TI  - Phenotypic and functional assessment of intraepithelial lymphocytes bearing a
      'forbidden' alpha beta TCR.
AB  - Differences in the surface antigen phenotype, such as the expression CD8 as an
      alpha alpha homodimer or the lack of Thy-1, on intestinal intraepithelial
      lymphocytes (IEL) are related, in part, to alternative differentiation pathways.
      The relationship of IEL lacking the pan-T cell marker CD5 to these IEL, their TCR
      repertoire and function has not been examined directly. We explored the TCR
      repertoire and function of the CD5- IEL subset in relation to the expression of
      the 'autospecific' V beta 6 TCR in MIs-1a mice and to gamma delta TCR. The
      results indicate that CD5 expression was absent on the majority of TCR gamma
      delta IEL (96.9%) and on a significant proportion of TCR alpha beta IEL (25.0%).
      Virtually all IEL in DBA/2 (MIs-1a) mice that expressed the 'autospecific' V beta
      6 TCR were CD5-, and this correlated with the expression of CD8 alpha alpha. To
      assess the functional capacity of this subset of IEL, we examined proliferation
      and IL-2 production in response to TCR activation. Although CD5- IEL proliferated
      in response to anti-CD3, IEL bearing TCR V beta 6, in MIs-1a mice, were not
      responsive to TCR-mediated activation. Similarly, TCR gamma delta IEL were not
      responsive to stimulation by anti-TCR gamma delta antibodies. The addition of
      exogenous IL-2, however, reconstituted the proliferative response of both TCR
      gamma delta IEL and the TCR V beta 6 expressing IEL. We conclude that the lack of
      CD5 defines a unique subset of intraepithelial T cells expressing either TCR
      gamma delta or alpha beta that include potentially autoreactive cells that remain
      anergic in the absence of IL-2.

PMID- 7530038
TI  - Rapid establishment of a stable IL-4/IFN-gamma production profile in the antigen
      specific CD4+ T cell response to protein immunization.
AB  - Development of the antigen-specific murine T cell response to immunization with
      keyhole limpet hemocyanin (KLH) in adjuvant has been monitored with direct
      limiting dilution analysis of CD4+ cells in draining lymph nodes (LN) and
      measurement of the cytokines produced by their clonal progeny. In vivo, the
      response to immunization suggested a major role for IL-4 and a minor role for IFN
      gamma since IL-4 mRNA levels increased and IFN-gamma mRNA levels declined in LN
      over the first 3 days, and KLH-specific serum antibodies were mainly of IgG1
      class with lower levels of IgE and IgG2a. Antigen-specific clonogenic cells were
      first detected in LN at day 4, at which time they comprised approximately 8% of
      the total CD4+ LN cell pool, declining to 1-2% from day 7 until at least 6 weeks
      after immunization. These clonogenic cells expressed high levels of surface CD44
      (Pgp-1) both early and late in the in vivo response. Over the whole of the time
      span from day 4 to 6 weeks after immunization, most antigen-specific cells gave
      rise to clones that secreted IL-4 and a smaller proportion gave rise to IFN-gamma
      secreting clones. By contrast, polyclonally activated CD4+ cells from untreated
      mice preferentially gave rise to clones with the converse cytokine profile. We
      conclude that a stable ratio of antigen-specific CD4+ cells committed to IL-4 or
      IFN-gamma synthesis is established within the first 4 days after KLH immunization
      and, contrary to prediction, does not evolve towards a more restricted cytokine
      profile during the primary response.

PMID- 7530039
TI  - Differential ability of Th1 and Th2 T cells to express Fas ligand and to undergo
      activation-induced cell death.
AB  - Stimulation of previously activated T cells through the antigen receptor can
      result in the apoptotic death of the responding cell, a process referred to as
      activation-induced cell death (AICD). This process appears to involve Fas (CD95)
      and its ligand (Fas-L). The distribution of Fas and Fas-L on various T cell
      subsets has not been extensively characterized. We have therefore analyzed cells
      committed to a Th1- or Th2-type differentiation pattern for the expression and
      function of Fas-L. Using both a sensitive bioassay and flow cytometry, we
      demonstrate that cloned Th1 cells express high levels of Fas-L, whereas cloned
      Th2 cells express only low levels. The expression of Fas-L by Th1 and Th2 cells
      correlates with the relative abilities of these two cell types to undergo AICD.
      Whereas AICD is readily observed in cultures of cloned Th1, but not Th2 cells,
      Th2 cells are capable of undergoing apoptosis in the presence of Th1 cells
      expressing Fas-L. The ability of T cells to undergo AICD appears to be unrelated
      to the presence of various cytokines. Thus, the Fas/Fas-L pathway appears to be
      critical for the induction of AICD and this pathway is differentially regulated
      in cells committed to either Th1 or Th2 differentiation.

PMID- 7530041
TI  - A new technique for simultaneous demonstration of 4 tumor-associated antigens in
      pancreatic cancer cells.
AB  - A new technique is presented for demonstration of 4 tumor-associated antigens in
      a single slide prepared from paraffin-embedded specimens that can be kept
      permanently. By sequential processing of the slides with monoclonal antibodies
      B72.3, DU-PAN-2, CO19-9 and CO17-1A, immunoreactivity with all 4 antibodies can
      be visualized. Examination of parallel slides stained only with one of the
      antibodies revealed no interference of the reactive products of the 4 antibodies
      with each other. Some tumor cells demonstrated reactivity with two antibodies.
      The described technique provides a possibility to investigate spatial
      distribution of antigens in tumor cells, and it may be useful for diagnosis,
      prediction of prognosis and a more appropriate tumor classification.

PMID- 7530040
TI  - IL-2 production by myofibroblasts from post-radiation fibrosis in breast cancer
      patients.
AB  - The origin of cell activation in post-radiation fibrosis and its chronic
      extension are still poorly understood. Since local IL-2 cancer treatment
      sometimes triggers intraperitoneal fibrosis we have analyzed three
      myofibroblastic cell strains from post-radiation skin fibrosis (FPR7, FPR10 and
      FPR15) for their interactions with IL-2. In these cells we have observed the
      surface expression of the two chains of the IL-2R (IL-2R alpha beta), the
      presence of the 0.9 kb transcript specific for the IL-2 gene and, by flow
      cytometry with anti-IL-2 mAbs, the presence of IL-2 immunoreactive material
      inside the cells up to 8 days after subculture. The FPR cell lines secreted IL-2,
      as determined by ELISA. The secreted IL-2 is biologically active since it
      sustains the proliferation of the IL-2-dependent murine lymphoid cell line CTLL2
      and preincubation with anti-IL-2 blocking mAbs completely abolishes this
      activity. Overnight incubation of FPR cells with polyclonal anti-IL-2 antibodies
      leads to a decreased expression of the membrane adhesion molecules ICAM-1 and
      CD44, suggesting the existence of an autocrine/paracrine loop involved in the
      surface expression of these antigens. By contrast, in normal adult skin
      fibroblasts we did not detect IL-2 gene activation. In vivo, IL-2 secretion by
      post-radiation fibrosis fibroblasts and the subsequent up-regulation of ICAM-1
      and CD44 may represent key events during the process that leads to radiation
      fibrosis.

PMID- 7530042
TI  - Lipid deposition in intestine as a possible cause of malabsorption of nutrients
      in zinc-deficient common carp (Cyprinus carpio).
AB  - An experiment was performed to examine the interaction between Zn deficiency and
      lipid intake in carp. The carp were given a high-lipid diet that was either Zn
      deficient (ZD) or Zn-supplemented (ZS), or were pair-fed (PF) the ZS diet to the
      intake of the ZD group. After 8 weeks the carp were killed and measurements were
      made of intestinal glucose uptake, levels of DNA, RNA and triacylglycerol, and
      alkaline phosphatase (EC 3.1.3.1) activity in liver and intestine samples. A
      further group of similar carp were given the same diets but at week 8 were
      transferred to low-lipid diets, with the exception of half the ZD group. After a
      further 8 weeks of treatment, carps were killed for biochemical studies.
      Intestinal [14C]glucose uptake, levels of DNA, RNA and alkaline phosphatase
      activity in intestine and liver were significantly (P < 0.05) lower in the high
      lipid ZD group than in the high-lipid ZS and PF diet groups. The triacylglycerol
      concentration in the intestine was higher in the high-lipid ZD group than in the
      other two groups. When the carp were given the corresponding low-lipid diets, the
      variables measured in intestine and liver of the ZD group were close to those of
      the other groups. The results of this study demonstrate that lipid, when present
      in excess in the diet, accumulates in the intestine under Zn-deficient conditions
      and may reduce the absorption of glucose in carp. The reduced RNA and DNA levels
      and alkaline phosphatase activity in liver and intestine of ZD fish compared with
      those of ZS fish given high-lipid diets is proposed to be due to the
      malabsorption of nutrients linked with lipid deposition in the intestine, rather
      than their dependence on the level of Zn in the diet.

PMID- 7530043
TI  - Direct determination of the sequence recognition requirements of the SH2 domains
      of SH-PTP2.
AB  - SH-PTP2 is a widely-expressed protein tyrosine phosphatase with two tandem SH2
      (src homology 2) domains and a C-terminal catalytic domain. Glutathione S
      transferase fusions of the SH2 domains alone and of a catalytically inactive full
      length mutant were made, and binding assays were developed using the purified
      fusion proteins to directly determine what residues are involved in the
      recognition of binding targets by the SH2 domains. The binding kinetics of the
      SH2 domains to a phosphotyrosyl-containing peptide of the sequence surrounding
      Tyr1009 of the platelet-derived growth factor receptor (PDGFR) beta subunit
      [DTSSVL(pY)TAVQPN] were determined by surface plasmon resonance, confirming that
      this is a high-affinity binding ligand. Using various N- and C-terminal
      truncations of this peptide as competitors in the binding assays, the minimum
      peptide that served as a high-affinity binding ligand was found to be VL(pY)TAV.
      Systematic Ala substitutions of this peptide indicated that in addition to the
      phosphotyrosine (pY), the critical residues for recognition and binding are at pY
      + 1 and pY + 3 as previously reported, and notably at pY-2 as well. Binding
      competition results with these and other PDGFR, IRP, and IRS-1 peptides suggested
      some general rules for sequence recognition by the SH2 domains of SH-PTP2.
      Peptides that bind to the SH2 domains in the binding assays were also found to
      stimulate the phosphatase activity of SH-PTP2.

PMID- 7530044
TI  - 1-beta-D-arabinofuranosylcytosine activates tyrosine phosphorylation of p34cdc2
      and its association with the Src-like p56/p53lyn kinase in human myeloid leukemia
      cells.
AB  - Recent studies have demonstrated that treatment of human myeloid leukemia cells
      with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with activation of
      serine/threonine protein kinases and early response gene expression. The present
      work has examined the involvement of protein tyrosine phosphorylation in ara-C
      induced responses of HL-60 myeloid leukemia cells. The results of
      immunoprecipitation studies demonstrate that HL-60 cells respond to ara-C with
      tyrosine phosphorylation of the cell cycle regulatory protein p34cdc2 and a
      decrease in the activity of this kinase. This effect was detectable at 15 min of
      ara-C exposure. Coimmunoprecipitations with anti-p34cdc2 support binding of this
      protein to the Src-like p56/p53lyn tyrosine kinase in ara-C-treated, but not
      untreated, cells. The results further demonstrate that ara-C treatment is
      associated with a dose-dependent activation of p56/p53lyn and that ara-C-induced
      p56/p53lyn activity is blocked by the protein tyrosine inhibitors herbimycin A
      and genistein. Studies with a glutathione S-transferase-Lyn fusion protein
      confirm interaction of p34cdc2 and p56/p53lyn in lysates of ara-C-treated cells.
      Moreover, we demonstrate that (1) p56/p53lyn phosphorylates Tyr-15 of p34cdc2 in
      vitro and (2) phosphorylation of p34cdc2 by p56/p53lyn inhibits p34cdc2 activity.
      These findings indicate that the cellular response to ara-C includes activation
      of p56/p53lyn and that association of p56/p53lyn with p34cdc2 may contribute to
      regulation of the cell cycle progression in ara-C-treated cells.

PMID- 7530045
TI  - Macrophage NO synthase: characterization of isolated oxygenase and reductase
      domains reveals a head-to-head subunit interaction.
AB  - Macrophage NO synthase (NOS) is a dimeric enzyme comprising two identical 130 kDa
      subunits and contains iron protoporphyrin IX (heme), tetrahydrobiopterin, FAD,
      FMN, and calmodulin. We have carried out limited proteolysis to locate the
      domains involved in prosthetic group binding and subunit interaction. Trypsin
      cleaved the subunits of dimeric macrophage NOS at a single locus, splitting the
      enzyme into two fragments whose denatured molecular masses were 56 and 74 kDa.
      The smaller fragments remained dimeric in their native form (112 kDa), contained
      heme and tetrahydrobiopterin, and could bind L-arginine, CO, or imidazole. In
      contrast, the larger fragments were monomeric in their native form, contained
      FAD, FMN, and CAM, and bound NADPH. Although neither purified fragment alone or
      in combination catalyzed NO synthesis from L-arginine, the flavin-containing
      fragment did catalyze cytochrome c reduction at a rate that was equivalent to
      that of native dimeric NOS. These results indicate that trypsin cuts macrophage
      NOS into two domains that can exist and function independently of one another.
      The domain that binds heme, H4biopterin, and substrate is also responsible for
      maintaining the NOS dimeric structure, while the domain containing FAD, FMN, and
      CAM is not required for subunit interaction. This suggests a structural model for
      macrophage NOS in which the subunits align in a head-to-head manner, with the
      oxygenase domains interacting to form a dimer and the reductase domains existing
      as independent extensions.

PMID- 7530046
TI  - Lipid-peptide interface: valine conformation and dynamics in the gramicidin
      channel.
AB  - High-resolution dynamic and structural characterizations have been achieved for
      each of the valine side chains of the gramicidin channel while solubilized in
      hydrated lipid bilayers. The characterizations have been achieved by 2H NMR
      spectra of both oriented and unoriented samples obtained at 36 and 5 degrees C,
      respectively. Powder patterns displaying intermediate time frame averaging
      provide dynamic information, and quadrupole splittings from aligned samples
      provide orientational constraints for the side chain structure. Librational
      amplitudes for each site throughout the side chain have also been characterized.
      Val6 and Val8 are shown to be fixed in rotameric states, potentially constraining
      two of the indole rings and the functionally important indole dipole moment
      orientations. Val1 and Val7 undergo three-state jump motions. The jump
      frequencies increase from the microsecond to nanosecond time frame upon
      increasing the temperature through the lipid phase transition. For the same
      temperature range, there is no evidence for changes in conformational state
      populations. Despite small differences in the substate populations for the two
      residues, the motions may be loosely coupled as indicated by the high-resolution
      structure.

PMID- 7530048
TI  - Binding of sialyl Lewis x to E-selectin as measured by fluorescence polarization.
AB  - Fluorescence polarization has been used to directly measure the binding of the
      tetrasaccharide sialyl Lewisx (sLe(x)[Glc], or NeuAc alpha 2-3Gal beta 1-4[Fuc
      alpha 1-3]Glc) to a soluble form of E-selectin, a member of the class of adhesion
      molecules that plays an important role in immune-cell response to inflammation.
      The experiments utilized a fluorescent derivative of sLe(x)[Glc] with fluorescein
      attached directly to the glucose residue through a beta-glycosidic linkage. The
      resulting fluorescent sLe(x) was shown to inhibit binding of HL60 cells to
      immobilized E-selectin and exhibited fluorescence polarization enhancement in the
      presence of a monovalent form of a recombinant soluble E-selectin-Fc chimera.
      Thermodynamic dissociation constants of 107 +/- 26 and 120 +/- 31 microM were
      obtained for the fluorescent sLe(x)[Glc] and the free sLe(x)[Glc] sugars,
      respectively. These results demonstrate that E-selectin interacts weakly with the
      minimal carbohydrate recognition determinant sLe(x). Additional binding
      interactions through the action of the authentic coreceptor or via clustering of
      the ligand and E-selectin molecules on the respective neutrophil and endothelial
      cell surfaces may also play a role in the overall cellular binding strength.
      However, the basic interaction between carbohydrate and protein appears weak,
      consistent with other carbohydrate-protein interactions studied to date.

PMID- 7530047
TI  - Eosin, a potent inhibitor of the plasma membrane Ca pump, does not inhibit the
      cardiac Na-Ca exchanger.
AB  - The Na-Ca exchanger and the sarcolemmal/plasma membrane (SL(PM)) Ca pump are the
      two major pathways for Ca transport to the extracellular space in many cells. In
      cardiac myocytes, the Na-Ca exchanger appears to be responsible for a greater
      portion of this Ca flux [Bassani, R. A., et al. (1992) J. Physiol. 453, 591-608].
      However, the respective contributions of these two transporters are not as well
      defined in all tissues (e.g., smooth muscle). We propose that eosin
      (tetrabromofluorescein) may be a useful tool for quantitatively determining the
      proportion of Ca transported by the Na-Ca exchanger vs the SL(PM) Ca pump in
      various cells. Eosin is the most potent inhibitor known for the SL(PM) Ca pump
      (IC50 approximately 0.3 microM in red blood cell inside-out vesicles); unlike the
      Na/K and H/K pumps, eosin does not compete with ATP for the SL(PM) Ca pump
      [Gatto, C., & Milanick, M. A. (1993) Am. J. Physiol. 264, C1577-C1586]. In the
      present study, we have shown that eosin was a potent inhibitor of the cardiac
      SL(PM) Ca pump (IC50 approximately 1 microM); in contrast, eosin (< or = 20
      microM) did not inhibit the cardiac Na-Ca exchanger. In experiments where Ca was
      being transported by both the SL(PM) Ca pump and the Na-Ca exchanger
      simultaneously, eosin effectively eliminated the Ca pump-mediated transport. In
      addition, we show that eosin can permeate the human red cell membrane; cell
      permeability is an attractive feature for using eosin in whole cell studies. We
      conclude that eosin can be used for determining the role that the SL(PM) Ca pump
      plays in whole cell Ca homeostasis.

PMID- 7530049
TI  - Design of artificial short-chained RNA species that are replicated by Q beta
      replicase.
AB  - Different RNA species that are replicated by Q beta replicase have related
      secondary structures: for both plus and minus strands, "leader" stem structures
      were found at their 5' termini, while their 3' termini were unpaired. Parallel
      structures in complementary strands rather than antiparallel ones require the
      occurrence of wobble pairs and other imperfections in the stem regions. To test
      whether the leader structures are required for replication, artificial RNA
      sequences were synthesized by transcription from synthetic oligodeoxynucleotides
      with T7 RNA polymerase and assayed for their ability to be replicated by Q beta
      replicase. A synthetic short RNA species known to be replicated was amplified,
      forming a stable quasi-species; i.e., its sequence was conserved during hundreds
      of replication rounds. A synthetic mutant of this sequence that stabilized the
      leader in one strand but favored a 3'-terminal stem in the other one led to the
      complete loss of template activity. When new RNA sequences with the described
      structural requirements were designed and synthesized, their template activity
      was too low to be directly measurable; however, incubation with replicase
      produced replicating RNA whose sequence was closely related to the synthesized
      RNA species. The most likely interpretation is that the designed sequences were
      in a low montainous region in the replication fitness landscape and were
      optimized during amplification by Q beta replicase to a nearby fitness peak. The
      structural features postulated to be required for replication were not only
      conserved but even improved in the outgrowing mutants.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 7530050
TI  - Characterization of the nuclease activity of Drosophila Rrp1 on phosphoglycolate-
      and phosphate-modified DNA 3'-termini.
AB  - Drosophila Rrp1 includes a carboxy-terminal region homologous to Escherichia coli
      exonuclease III which is sufficient to repair both oxidative and alkylation
      damage to DNA. An apurinic/apyrimidinic endonuclease activity intrinsic to Rrp1
      was characterized previously. In this work, the 3'-phosphodiesterase and 3'
      phosphatase activities of Rrp1 are demonstrated and characterized.
      Phosphoglycolate- and phosphate-modified DNA 3'-termini are formed by oxygen
      radical induced DNA cleavage. To demonstrate the 3'-phosphodiesterase activity of
      Rrp1, a 3'-phosphoglycolate-terminated oligonucleotide substrate was generated by
      site-specific cleavage of a unique GpC dinucleotide by iron(II) bleomycin.
      Removal of the terminal phosphoglycolate is detected by mobility shift on a DNA
      sequencing gel. Rrp1 cleaves the phosphoglycolate and releases a product with a
      3'-hydroxyl terminus. Phosphoglycolate is removed more readily than the 3'
      terminal dGMP residue. Rrp1 phosphodiesterase activity is not inhibited by 120 mM
      NaCl, while the 3'-exonuclease is reduced 25-fold. Using a 3'-phosphate
      terminated oligonucleotide, the phosphatase activity of Rrp1 is at least 25-fold
      lower than its phosphodiesterase or apurinic endonuclease, and 56-fold lower than
      exonuclease III activity on the identical substrate. Rrp1 3'-phosphatase is
      reduced 25-fold by 80 mM NaCl. These results were confirmed using an assay that
      measures the ability of Rrp1 to stimulate DNA synthesis on circular DNA
      substrates nicked by various DNA damage treatments. In that assay, Rrp1 poorly
      repairs 3'-phosphate-terminated nicks introduced by micrococcal nuclease. The
      significance of these enzymatic properties for the biological of Rrp1 is
      discussed.

PMID- 7530051
TI  - Involvement of Neurospora mitochondrial tyrosyl-tRNA synthetase in RNA splicing.
      A new method for purifying the protein and characterization of physical and
      enzymatic properties pertinent to splicing.
AB  - The Neurospora CYT-18 protein, the mitochondrial tyrosyl-tRNA synthetase,
      functions in the splicing of group I introns. Here, bacterially expressed CYT-18
      protein, purified by a new procedure involving polyethyleneimine precipitation to
      remove tightly bound nucleic acids, was used to characterize properties pertinent
      to RNA splicing. Analytical ultracentrifugation and other methods showed that the
      CYT-18 protein is an asymmetric homodimer. The measured frictional ratio, f/fo =
      1.55, corresponds to an axial ratio of 10 for a prolate ellipsoid or 12 for an
      oblate ellipsoid. Like bacterial TyrRSs, the CYT-18 protein exhibits half-sites
      reactivity, each homodimer having one active site for tyrosyl adenylation and RNA
      splicing. The splicing activity of CYT-18 was unaffected by aminoacylation
      substrates at concentrations used in aminoacylation reactions, whereas the TyrRS
      activity was inhibited by physiological concentrations of the splicing cofactor
      GTP, as well as CTP or UTP, or by low concentrations of a group I intron RNA.
      Kinetic measurements suggest that the binding of CYT-18 to a group I intron
      substrate is a two-step process, with an initial biomolecular step that is close
      to diffusion limited (3.24 +/- 0.03 x 10(7) M-1s-1) followed by a slower
      conformational change (0.54 +/- 0.07 s-1). After CYT-18 binding, splicing occurs
      at a rate of 0.0025 s-1, within 6-fold of the rate of self-splicing of the
      Tetrahymena large rRNA intron in vitro. The Kd for the complex between the CYT-18
      protein and a group I intron substrate, calculated from koff/kon, was < 0.3 pM,
      substantially lower than determined by presumed equilibrium measurements [Guo,
      Q., & Lambowitz, A. M. (1992) Genes Dev. 6, 1357-1372]. As a result of this tight
      binding, the CYT-18 protein functions stoichiometrically in in vitro splicing
      reactions due to its extremely slow dissociation from the excised intron RNA. The
      very tight binding of the CYT-18 protein to the intron RNA raises the possibility
      that specific mechanisms exist for dissociating the protein from the excised
      intron in vivo.

PMID- 7530052
TI  - Human platelets have cholesteryl ester hydrolytic activity resulting in
      esterification of [1-14C]oleate to individual phospholipids of platelets.
AB  - Human platelet cholesteryl ester hydrolytic (CEH) activity was determined toward
      cholesteryl [1-14C]oleate resulting in esterification of [1-14C]oleate to
      individual platelet phospholipids: choline-containing phospholipids (PC);
      ethanolamine-containing phospholipids (PE); phosphatidylserine (PS);
      phosphatidylinositol (PI); and sphingomyelin (SPH). Liberation of [1-14C]oleate
      and esterification of [1-14C]oleate to platelet phospholipids was enhanced by 100
      nM iloprost (a stable analogue of prostacyclin that increases platelet cyclic
      adenosine monophosphate (c-AMP)), inhibited by 30 microM H-89 (N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide)) (a specific c-AMP dependent
      protein kinase (CADPK) inhibitor) and 500 microM 2',5' dideoxyadenosine (DDA) (an
      inhibitor of iloprost-induced rise in platelet c-AMP), but unaffected by 150 mM
      choloroquine diphosphate. These observations suggest that the CEH activity is
      mediated by a CADPK phosphorylation of an enzyme with the phosphorylated state
      representing the active form of the enzyme and that the CEH activity is
      extralysosomal.

PMID- 7530053
TI  - Management of follicular lymphoma.
AB  - Despite the fact that a small proportion of patients with follicular lymphoma may
      be alive 20 years after the initial diagnosis, and that it is repeatedly, albeit
      usually only partially, responsive to relatively mild therapy, the disease
      remains stubbornly incurable for the majority. Therefore, the testing of several
      new therapeutic approaches is welcome. Interferon has been investigated in two
      settings: in combination with conventional therapy and as "maintenance" following
      chemotherapy. Prolongation of remission duration has been demonstrated and one
      study shows a survival advantage. The purine analogue fludarabine, having
      originally been shown to induce remissions in patients with chronic lymphocytic
      leukemia, is also effective in follicular lymphoma, although its precise role
      remains to be determined. Myeloablative therapy with autologous bone marrow
      transplantation (which has been the subject of much debate and controversy in the
      context of low-grade lymphoma), has been shown to prolong duration of remission,
      although presently, there is no survival advantage. Finally, radiolabeled
      antibody therapy is showing promise in patients in whom other treatment
      modalities have failed. The significance of "minimal residual disease" manifest
      as circulating t(14;18)-containing cells, as demonstrated by polymerase chain
      reaction analysis awaits clarification.

PMID- 7530056
TI  - Mantle cell lymphoma with the features of mucosa-associated lymphoid tissue
      (MALT) lymphoma in an HTLV-I-seropositive patient.
AB  - A case of small lymphocytic B-cell lymphoma with seropositivity for human T-cell
      leukemia virus type I (HTLV-I), whose clinical features were closely related to
      those of mucosa-associated lymphoid tissue (MALT) lymphoma, is presented. The
      neoplastic cells of the lymph node were immunologically positive for CD5, in
      addition to several B-cell markers, but negative for CD10, and cytogenetically
      carried a t(11;14)(q13;q32). These findings were fully consistent with so-called
      mantle cell lymphoma (MCL). In addition to the lymph nodes and bone marrow,
      multiple extranodal sites including lacrimal and salivary glands, lung and
      stomach (where MALT is present) were occupied by lymphoma cells. These extranodal
      lesions were immunologically identical to the lymph nodes (CD5(+), CD10(-)), but
      histologically showed lymphoepithelial lesions (LEL) characteristic of MALT
      lymphoma. These findings suggest a possible relationship between MCL and MALT
      lymphoma, and the neoplastic cells are thought to originate from the CD5-positive
      B cells, which are present near the areas across the mantle and marginal zones.
      Furthermore, HTLV-I-infection, which appears to create an immunodeficient state
      or modulate the B-cell response, is thought to play a role in B-cell
      lymphomagenesis.

PMID- 7530058
TI  - Insulin cooperates with IL-1 in regulating expression of alpha 1-acid
      glycoprotein gene in rat hepatoma cells.
AB  - Insulin treatment of the rat hepatoma H-35 cells results in a reduced stimulation
      of acute phase plasma protein gene expression by IL-1- and IL-6-type cytokines.
      The cell response to insulin appears to involve both stimulatory and inhibitory
      regulatory mechanisms because a clonal variant line of the H-35 cells has been
      identified in which insulin increases specifically the IL-1 stimulation of alpha
      1-acid glycoprotein (AGP) gene, while still reducing the expression of the other
      acute phase protein genes. The magnitude of insulin and cytokine effect is
      dependent upon the proliferation state of the cell culture. One of the genetic
      targets of the insulin stimulation has been located to the cytokine-response
      element of the AGP gene and involves a cooperativity with the 5' adjacent IL-1
      responsive element. The molecular mechanism of insulin inhibition, however,
      remains to be identified.

PMID- 7530057
TI  - NMR and molecular modeling investigations of the neuropeptide substance P in the
      presence of 15 mM sodium dodecyl sulfate micelles.
AB  - To better understand the structural basis of the biological activity of the
      neuropeptide substance P SP; (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2),
      two-dimensional nmr spectroscopy experiments and simulated annealing calculations
      were used to investigate the conformation adopted in the presence of the membrane
      model system sodium dodecyl sulfate. It was determined that SP in the presence of
      SDS micelles undergoes a conformational equilibrium between an alpha- and a 3(10)
      helix involving the midregion (Pro4-Gln5-Gln6-Phe7-Phe8) of the peptide. The C
      terminus adopts an extended conformation while the N-terminus remains quite
      flexible. The conformation adopted by SP in the presence of SDS micelles yields a
      structure that is consistent with the model of a neurokinin-1 selective ligand
      proposed by Convert.

PMID- 7530054
TI  - Expression of the Fas antigen on primary human leukemia cells.
AB  - The antigen defined by the monoclonal antibody anti-Fas can mediate apoptosis, is
      associated with the receptor for tumor necrosis factor, and is expressed on a
      limited number of human tissues. In this study we analyzed the expression of Fas
      on primary human leukemic cells and on mononuclear cells from other hematologic
      disorders. A total of 95 samples of blood or bone marrow were studied by indirect
      immunofluorescence. These samples included the normal controls, 47 cases of acute
      myelogenous leukemia (AML), 11 cases of acute lymphoblastic leukemia (ALL), 21
      cases of leukemic lymphoma, seven cases of chronic myelogenous leukemia (CML),
      five cases of plasma cell leukemia or multiple myeloma, and five cases of
      myelodysplastic or myeloproliferative syndromes. Normal controls were negative
      without exception. Among AML, 13/47 cases (28%) were positive; among ALL, 1/11
      cases (9%) was positive; among leukemic lymphomas, 3/21 cases (14%) were
      positive. In a case of plasma cell leukemia which strongly expressed the Fas
      antigen, we demonstrated that the antibody mediates cell lysis, which was
      synergistically enhanced by the addition of rabbit complement. In patients with
      AML, Fas positivity had no obvious clinical relevance. Taken together, our
      results show that approximately 30% of cases of AML and occasionally other
      leukemias express the Fas antigens, whereas normal controls are negative in our
      test system. These findings may be useful in the treatment of refractory
      leukemias or may permit the purging of autologous transplants.

PMID- 7530059
TI  - Interleukin 1 beta induces diabetes and fever in normal rats by nitric oxide via
      induction of different nitric oxide synthases.
AB  - Substantial in vitro evidence suggests that nitric oxide may be a major mediator
      of interleukin 1 (IL-1) induced pancreatic beta-cell inhibition and destruction
      in the initial events leading to insulin-dependent diabetes mellitus. Using NG
      nitro-L-arginine methyl ester, an inhibitor of both the constitutive and the
      cytokine inducible forms of nitric oxide synthase, and aminoguanidine, a
      preferential inhibitor of the inducible form of nitric oxide synthase, we
      investigated the impact of inhibiting nitric oxide production on food-intake,
      body weight and temperature, blood glucose, plasma insulin, glucagon,
      corticosterone and leukocyte- and differential-counts in normal rats injected
      once daily for 5 days with interleukin 1 beta (IL-1 beta) (0.8 microgram/rat =
      4.0 micrograms/kg). Inhibition of both the constitutive and the inducible forms
      of nitric oxide synthase prevented IL-1 beta-induced fever, hyperglycaemia,
      hypoinsulinemia, and hyperglucagonemia, and partially prevented lymphopenia and
      neutrophilia, but had no effect on IL-1 beta-induced anorexia and changes in
      plasma corticosterone. Preferential inhibition of the inducible form of nitric
      oxide synthase using two daily injections of 5 mg/rat of aminoguanidine prevented
      IL-1 beta-induced hyperglycaemia and hypoinsulinaemia, and slightly reduced the
      pyrogenicity of IL-1 on 3 out of 5 days. Higher doses of aminoguanidine (100
      mg/rat) prevented lymphopenia and neutrophilia. We conclude that nitric oxide
      produced by the inducible form of nitric oxide synthase, mediates the IL-1 beta
      induced inhibition of insulin release and that the effect of IL-1 beta on
      temperature, pancreatic alpha-cells, and leukocyte differential counts seems to
      be mediated by nitric oxide produced by the constitutive form of nitric oxide
      synthase.

PMID- 7530055
TI  - Relationship of microparticles with beta 2-glycoprotein I and P-selectin
      positivity to anticardiolipin antibodies in immune thrombocytopenic purpura.
AB  - We investigated the association of beta 2-glycoprotein I and P-selectin with
      platelet-derived microparticles in 48 patients with immune thrombocytopenic
      purpura and 20 normal controls using two-color flow cytometric analysis. In
      addition, anticardiolipin antibodies were detected by an enzyme-linked
      immunosorbent assay. Platelet microparticles from the patients showed a higher
      positivity for beta 2-glycoprotein I than those from the normal controls (23.1 +/
      15.4% vs. 5.3 +/- 3.1%, p < 0.01), but this positivity was not related to the
      presence of platelet-associated IgG or to the severity of thrombocytopenia. In
      the 18 patients with more than 20% P-selectin-positive microparticles, beta 2
      glycoprotein I positivity was significantly higher than in the 30 patients with
      less than 20% P-selectin-positive microparticles (37.1 +/- 20.5% vs. 21.5 +/-
      17.3%, p < 0.01). In addition, anticardiolipin antibodies were detected in eight
      patients, and they had a significantly higher level of beta 2-glycoprotein I
      positive microparticles than the patients without such antibodies (42.0 +/- 22.9%
      vs. 22.6 +/- 18.9%, p < 0.05). Our results suggest that anticardiolipin
      antibodies activate platelets in immune thrombocytopenic purpura and cause the
      generation of microparticles rich in beta 2-glycoprotein I and P-selectin. These
      microparticles may then act to regulate coagulation abnormalities in patients
      with anticardiolipin antibodies.

PMID- 7530060
TI  - LPS-induced release of IL-1 beta, IL-6, IL-8, TNF-alpha and sCD14 in whole blood
      and PBMC from persons with high or low levels of HDL-lipoprotein.
AB  - We have examined basal and lipopolysaccharide (LPS)-induced release of
      interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL-8),
      tumour necrosis factor-alpha (TNF-alpha) and soluble CD14 (sCD14) in whole blood
      and peripheral blood mononuclear cells (PBMC) from 20 persons with either high
      (1.62-2.47 mmol/L) or low (0.43-1.29 mmol/L) levels of high-density lipoprotein
      (HDL). Whole blood was incubated at 37 degrees C for 2 h with 100 ng LPS/ml,
      while PBMC were incubated with 100 ng LPS/ml for up to 160 h. The LPS-induced
      release of IL-1 beta, IL-6, IL-8 and TNF-alpha into plasma showed no differences
      between the two HDL-groups; whereas levels of sCD14 were significantly higher in
      plasma in persons with low HDL (P < 0.01). PBMC incubated with LPS showed a
      significantly higher release of IL-1 beta (P = 0.01) and IL-6 (P = 0.02) in
      persons with high HDL at all sampling times. sCD14 was found not to be released
      by PBMC. These findings indicate that PBMC from persons with high or low levels
      of HDL have different functional properties, possibly of importance in
      inflammation and atherogenesis.

PMID- 7530061
TI  - Analysis of nucleotide sequences of hepatitis C virus isolates from husband-wife
      pairs.
AB  - To identify the route of hepatitis C virus (HCV) transmission, we investigated
      the sexual transmission of HCV by examining HCV markers among spouses of patients
      with chronic liver disease (CLD) due to HCV. Of 83 spouses, 14 (16.9%) had
      elevated serum aspartate aminotransferase or alanine aminotransferase, 20 (24.1%)
      had detectable anti-HCV antibodies, and 17 (20.5%) had measurable HCV-RNA in
      serum. However, the seropositivity rate of anti-HCV antibodies (24.1%) of
      patients' spouses was not significantly higher than that (15.4-27.5%) of an
      unselected population in the same district. Ten patient-spouse pairs underwent
      nucleotide sequence analysis of the HCV core and envelope genes. Overall the
      sequence homology of 10 couples (91.1%) was not significantly higher than that of
      10 randomly chosen unrelated pairs (88.2%). As reported earlier, in an age and
      sex matched case-control study of HCV transmission, a history of surgery is a
      prominent HCV risk factor. These results suggest that sexual transmission of HCV
      is rare.

PMID- 7530062
TI  - The Loeffler's methylene blue stain: an inexpensive and rapid method for
      detection of Helicobacter pylori.
AB  - Loeffler's methylene blue, commonly used as a counter-stain for acid fast
      bacilli, was used to detect Helicobacter pylori in paraffin sections and touch
      smears of gastric mucosal biopsies from 15 patients with duodenal ulcer and 35
      with non-ulcer dyspepsia, and the results were compared with the modified Giemsa
      stain. The time taken to stain smears by Loeffler's methylene blue was
      approximately 10 min and the results correlated well with those stained by the
      modified Giemsa stain. However, the Loeffler's methylene blue method was found to
      be simpler, quicker and cheaper than the modified Giemsa stain.

PMID- 7530063
TI  - Involvement of hypothalamic substance P in the effect of prolactin on dopamine
      release.
AB  - In order to examine the role of hypothalamic SP in the feedback regulation of
      prolactin, we studied the effect of prolactin and dopamine on SP concentration
      and release, and the effect of SP on dopamine release. Hypothalamic fragments
      from male Wistar rats were incubated in the presence of prolactin, dopamine or SP
      under basal and K(+)-stimulated conditions. SP (10(-7) M) stimulated dopamine
      release, while dopamine (10(-7) M) decreased SP content and release. Prolactin
      (100 ng ml-1) increased SP content and release. An increase in hypothalamic SP
      content was also found during suckling. In addition, a specific antagonist for
      SP, Win 62,577, blocked the effect of prolactin and dopamine release. These
      results show an interaction between SP and dopamine at the hypothalamic level and
      suggest that SP could mediate the feedback action of prolactin on dopamine
      release.

PMID- 7530066
TI  - Construction of a new teichuronopeptide-defective derivative from alkaliphilic
      Bacillus sp. C-125 by cell fusion.
AB  - Cell walls of facultative alkaliphilic Bacillus sp. C-125 are composed of
      peptidoglycan, teichuronic acid, and teichuronopeptide. A mutant lacking
      teichuronic acid, or defective in both teichuronic acid and teichuronopeptide has
      been isolated from the organism. We now constructed another type of a cell-wall
      defective mutant that was defective in teichuronopeptide but had teichuronic
      acid, by cell fusion using protoplasts prepared from a wild-type strain and a
      mutant defective in teichuronopeptide and teichuronic acid. This mutant grew more
      poorly than wild type or a teichuronic acid-defective strain of C-125. The
      growth, however, was faster than that of the parental strain defective in both
      teichuronic acid and teichuronopeptide.

PMID- 7530065
TI  - Signal transduction in T lymphocytes of SLE patients: lectin-activated
      phosphorylation on tyrosine.
AB  - A comparative study of signal transduction through tyrosine phosphorylation
      process in peripheral blood lymphocytes from SLE patients and healthy subjects
      reveal some modifications in the phosphorylation pattern of SLE T lymphocytes.
      Thus, the level of constitutive tyrosine phosphorylation in resting SLE T
      lymphocytes is higher than in lymphocytes from healthy subjects. In SLE T
      lymphocytes, a cellular proteic substrate with an apparent molecular weight of
      about 37 kDa is constitutively phosphorylated. Some differences in the pattern of
      phosphorylation are obvious in lectin (Con A, PHA)-activated T lymphocytes. Thus,
      Con A activation enhances the phosphorylation of cellular substrates with
      molecular weight in the range of 55-80 kDa from SLE T lymphocytes. Moreover, the
      21 kDa substrate is also hyperphosphorylated after PHA activation of SLE
      lymphocytes.

PMID- 7530064
TI  - Inhibitory control of nitric oxide on the arginine-vasopressin and oxytocin
      response to hypoglycaemia in normal men.
AB  - In order to establish whether nitric oxide (NO) participates in the regulation of
      arginine-vasopressin (AVP) and/or oxytocin (OT) secretion in humans, six normal
      men were treated with placebo (normal saline) or the NO synthase inhibitor N,G
      nitro-L-arginine methyl ester (L-NAME), given at doses (40 micrograms kg-1
      injected plus 50 micrograms kg-1 infused i.v.) previously found to be unable to
      change blood pressure. Experiments were carried out both in basal conditions and
      during stimulation of posterior pituitary secretion with insulin (0.15 IU kg-1)
      induced hypoglycaemia. The administration of saline or L-NAME alone was unable to
      change basal AVP or OT levels. Insulin-induced hypoglycaemia, however, enhanced
      plasma AVP and OT levels by two-fold in the absence of L-NAME and by four-fold in
      the presence of the NO synthase inhibitor (NOS). Blood glucose levels decreased
      in a similar manner during the insulin tolerance tests, regardless of L-NAME
      administration. In all experiments, AVP and OT responses to hypoglycaemia
      followed a similar pattern, with mean peak levels at 45 min. These data suggest
      that in normal men NO is not involved in regulation of basal AVP and OT
      secretions, whereas it exerts an inhibitory role in the control of the posterior
      pituitary hormone responses to hypoglycaemia.

PMID- 7530068
TI  - Hepatitis C virus RNA and anti-N14 antibody levels during interferon alpha
      therapy for chronic hepatitis C.
AB  - To investigate the markers useful for evaluating the long-term efficacy of
      interferon (IFN) therapy, the quantity of hepatitis C virus (HCV) RNA and two
      anti-HCV antibody titers (anti-N14 and anti-C-100-3 antibody) in 21 chronic
      hepatitis C patients were determined. In all complete responders, a sustained
      clearance of the virus and reductions in the anti-HCV antibody titers were
      observed during and after therapy. In most of the temporary responders,
      reductions in the HCV RNA levels and in both anti-HCV antibody titers were
      observed temporarily during the therapy, and relapse followed. In nonresponders,
      although the HCV RNA levels and anti-N14 antibody titer tended to remain
      unchanged or increased during and after therapy, the anti-C-100-3 antibody titers
      showed no tendency. These results demonstrate that the monitoring of the HCV RNA
      level and anti-N14 antibody titer is clinically useful for following the
      patient's response to IFN therapy for chronic hepatitis C.

PMID- 7530070
TI  - Monosaccharide and oligosaccharide analysis of isoelectric focusing-separated and
      blotted granulocyte colony-stimulating factor glycoforms using high-pH anion
      exchange chromatography with pulsed amperometric detection.
AB  - In this study, a sensitive, straightforward technique is developed for the
      analysis of glycoprotein O-linked oligosaccharides. Specifically, O-linked
      oligosaccharides of granulocyte colony-stimulating factor (G-CSF) are analysed by
      separating charged glycoforms using isoelectric focusing, electroblotting to
      polyvinylidene difluoride, releasing monosaccharides and oligosaccharide alditols
      from the blotted glycoprotein bands, and producing chromatographs using high-pH
      anion-exchange chromatography with pulsed amperometric detection. Using this
      technique, the O-linked structures of G-CSF produced by recombinant Chinese
      hamster ovary (CHO) cells are deduced by comparison with monosaccharide and
      oligosaccharide standards. Lectin blotting and peptide sequencing support the
      identities of the presumed G-CSF glycoforms. The two major glycoforms determined
      using this methodology correspond to those determined previously for CHO-produced
      G-CSF using NMR. Additional glycoforms are also identified in this study,
      presumably resulting from the presence of N-glycolyneuraminic acid in place of N
      acetylneuraminic acid. The utility of this analytical approach is then
      demonstrated in an analysis of the effect of the extracellular environment on the
      O-linked glycosylation of G-CSF by recombinant CHO cells. Increasing the level of
      ammonium ion in the culture medium is shown to reduce the percentage of G-CSF
      produced with sialic acid linked alpha (2,6) to N-acetylgalactosamine.

PMID- 7530069
TI  - Drug eruption caused by recombinant human G-CSF.
AB  - Two types of recombinant human granulocyte colony-stimulating factor (rhG-CSF)
      are available, and equally used for mitigation of neutropenia. One is a
      glycosylated natural product from mammalian cells, and the other a non
      glycosylated form from Escherichia coli. Though only minimal adverse effects have
      been reported for both, we treated two patients with rhG-CSF-induced systemic
      eruption. Based on these patients, the following should be noted: 1) drug
      eruption may occur in both types of rhG-CSF without detectable antibodies, 2)
      intradermal test is useful for determination of the causal drug, and 3) if one
      rhG-CSF product causes eruption, the alternative one may possibly be safe and
      effective.

PMID- 7530071
TI  - Current status and future prospects for the treatment of lung disease in cystic
      fibrosis by gene therapy.

PMID- 7530067
TI  - Production and epitope specificity of monoclonal antibody against mouse
      peptidylarginine deiminase type II.
AB  - Peptidylarginine deiminase catalyzes the conversion of arginyl residues in
      proteins to citrullyl residues in the presence of Ca2+. We described the
      preparation of monoclonal antibody (subclass type IgG1) specific to mouse
      peptidylarginine deiminase type II. The antibody had no effect on the enzyme
      activity and its specific epitope was localized in the eight-residue segment at
      the amino-terminal portion of the enzyme.

PMID- 7530072
TI  - Cloning and expression in murine erythroleukemia cells: the soluble forms of the
      type I and type II tumor necrosis factor receptors fused to an immunogenic
      affinity tag.
AB  - We have cloned, expressed, and purified the extracellular domains of types I and
      II human tumor necrosis factor receptors. Both proteins were expressed in and
      secreted by murine erythroleukemia cells under the control of the human beta
      globin promoter placed down-stream from the human globin locus control region.
      Secretion of both proteins was directed by the respective tumor necrosis factor
      receptor signal sequence. Each tumor necrosis factor receptor extracellular
      domain was expressed as a chimeric protein, fused to a carboxy terminal flexible
      peptide linker and an antigenic affinity tag. Secretion of both proteins into the
      growth medium in a hollow fiber bioreactor was achieved. A monoclonal antibody
      generated against the affinity tag allowed the purification of both proteins.
      These were isolated as biologically active products in that they bound human
      tumor necrosis factor-alpha in a 125I-radioiodinated ligand binding assay. The
      two proteins also bound tumor necrosis factor-alpha at approximately equimolar
      ratios as demonstrated by BIAcore sensorgram analysis.

PMID- 7530073
TI  - [The neurophysiological correlates of the processes of decision making in the
      cerebral cortex during visual recognition in monkeys].
AB  - In behavioral experiments on monkeys tested for a delayed visual differentiation
      of different colours stimuli, neuronal pools were recorded simultaneously in the
      visual, prefrontal and inferotemporal cortex. Wrong motor responses were always
      followed by considerable readjustments of the unit activity patterns whereas in
      right decisions a synchronisation and a cross-correlation occurred between
      neuronal pools. Possible mechanisms of the decision making and the reasons for
      the desynchronisation in wrong responses, are discussed.

PMID- 7530074
TI  - [The role of capsaicin-sensitive afferent nerves in regulating carbohydrate
      metabolism in the liver].
AB  - Stimulation of afferent neurons with capsaicin enhanced the glycogen
      phosphorylase activity and decreased the glycogen contents in the rat liver. The
      glucose concentration in the blood serum was risen. Neurotoxic doses of capsaicin
      also enhanced the glycogen phosphorylase activity, more obviously so in adult
      rats. Preliminary administration of the toxic doses of capsaicin somewhat
      diminished the stimulating effect of capsaicin.

PMID- 7530075
TI  - [A chronobiological approach to assessing the role of the striatum in the origin
      of mental depression].

PMID- 7530077
TI  - [A programmed equipment unit for forming binaural acoustic signals].

PMID- 7530076
TI  - [The recovery of behavioral functions after the transplantation of embryonic
      striatum to the damaged amygdala in rats].

PMID- 7530078
TI  - [The circadian rhythm of fluctuations in the gonadoliberin level in the rat
      hypothalamus and the effect on it of different xenobiotics].
AB  - An obvious circadian rhythm of the gonadoliberine levels was found in the Organum
      vasculosum of Lamina terminalis: the level being very low in the morning, rising
      5-fold after midday and 10-fold at 5-6 p.m. The rhythm did not depend on the
      oestrous cycle stage and was not found in males. Xenobiotics interfere with the
      rhythm due, probably, to lowering of the suppressive tonus.

PMID- 7530079
TI  - [A device for the artificial ventilation of the lungs of a working subject].

PMID- 7530080
TI  - [Parallels in the development of the physiology schools of St. Petersburg and
      Kazan universities].

PMID- 7530081
TI  - [The structural basis of interaction in the striopallidum of the limbic and motor
      systems].
AB  - Limbic and motor areas with prevailing projections from respective subcortical
      structures, were revealed in the basal ganglia. An overlapping of the terminal
      fields of the initial neurons of both types of structures was found in
      considerable areas of the striopallidum. The data obtained on the organisation of
      projections of functionally different subcortical structures upon the
      striopallidum are regarded as the base of the functional heterogeneity of the
      basal ganglia and the interaction of limbic and motor systems in them.

PMID- 7530082
TI  - [Carboxypeptidase N and angiotensin-converting enzyme activities in the blood
      serum of rats with different resistances to emotional stress].
AB  - The carboxypeptidase N and angiotensin converting enzyme contents was 1.4-1.5
      fold higher in emotionally stable rats as compared with those predisposed to an
      emotional stress. Possible causes of this phenomenon are discussed.

PMID- 7530083
TI  - [The oxytocinergic neurosecretory system in genetically selected rats differing
      by their emotionality. Morphometric research].
AB  - The rats selectively bred for rapid (KHA) and slow (KLA) acquisition of the
      avoidance response were subjected to inescapable shock (IS). Synthesis and
      secretion of oxytocin (OT) were higher in intact KLA rats as compared to KHA
      ones. Preliminary exposure to IS resulted in opposite changes of the OT synthesis
      and secretion. The findings suggest a dependence of the stress-reactivity of the
      OT-ergic system on the copying of the behaviour strategy.

PMID- 7530084
TI  - [The alkaline phosphatase and K,Na-ATPase activities of the capillaries in the
      rat parietal cortex under conditions of reduced blood flow].
AB  - In acute reduction of circulation, the activity of capillary enzymes was found to
      be reduced as well. The reduced activity of the K,Na-ATPase in a later period was
      followed by the return to its normal level.

PMID- 7530085
TI  - [Somatostatin in the hypothalamic mechanism of control over prolactin and milk
      secretion].
AB  - The data obtained in lactating rats suggest existence of direct functional
      interrelationship between somatostatin and dopamine during the lactating period,
      both of them taking part in the control of prolactin synthesis and milk
      secretion. The findings permit to characterise somatostatin as one of the
      accessory mechanism of the hypothalamic control of prolactin synthesis and milk
      secretion.

PMID- 7530087
TI  - [The physiological role of the structural-functional changes in the air-blood
      barrier of the lungs in supplying the body with oxygen under the action of
      extreme factors].
AB  - Hypoxic states, under the effect of extreme factors, induced changes in the
      endothelium of the lung capillaries irrespective of the nature of the factors
      (exo- or endogenous) causing the hypoxic state. Significant changes of the
      mitochondrial apparatus of the lung air-blood barrier cells occurred in the
      hypoxic hypoxia. The data obtained suggest that the thickness of the ABB, under
      extreme conditions, cannot serve as a parameter of the morphofunctional state of
      the lung ABB. The compensatory-adaptive response of the cell structures seem to
      decrease the oxygen diffusion from the alveolar gas into the blood of the lung
      capillaries.

PMID- 7530088
TI  - [Erythrocyte lipids and gas exchange in the lungs].

PMID- 7530086
TI  - [The mechanisms of the rhythmic movements of the tracheal smooth-muscle wall
      during breathing].
AB  - Change of the lumen of respiratory pathways in breathing was shown to be
      determined by the electric and mechanical activity of the smooth muscle wall. The
      rhythmic activity of the smooth muscle is formed by the neuronal apparatus of
      intramural ganglia. The correlation of this apparatus work with the respiratory
      centre is performed via the efferents of the n. vagus.

PMID- 7530089
TI  - [Changes in the endotheliocyte activity of the coronary vessels under the
      influence of stress].
AB  - The effect of saponin and blockade of the nitrogen oxide upon the coronary
      endothelium was found in rats subjected to a 6-hrs stress. The damage of the
      endothelium and the blockade abolished the stressor-induced increase in the
      coronary blood flow velocity. The index of autoregulation and the latter's
      efficiency, however, remained the same. Preliminary administration of L-arginine
      prevented the effect of NG-monomethyl-L-arginine upon the coronary flow in the
      isolated hearts of rats subjected to stress. The post-stressor increase in the
      coronary blood flow seems to be due to an increase in releasing the nitrogen
      oxide from the coronary vessels' endotheliocytes.

PMID- 7530090
TI  - [The contribution of the myocardial segmental nonhomogeneity of the left
      ventricular walls to its contractile and pumping functions].
AB  - A normalised variation coefficient of the partial systolic fraction served as the
      measure of nonhomogeneity of the segmentary kinetics of the left ventricle's wall
      (parameter J). A significant correlation was found between the parameter J and
      the fraction of the ventricle output (the correlation being negative one) both in
      normal subjects and in patients with cardiac pathology. The parameter J was also
      found to be a sensitive index of the heart pumping and contractile functions. The
      local cardiotopodynamics as expressed via the segmentary nonhomogeneity seems to
      be able to contribute much into the regulation or modulation of the heart pumping
      function.

PMID- 7530092
TI  - [The temperature dependence of the postactivation changes in the mechanical
      parameters of the tetanic contraction of the rat gastrocnemius muscle].

PMID- 7530091
TI  - [Brain temperature in laboratory mice at different ambient temperatures].
AB  - The data obtained showed absence of a significant brain/body temperature
      difference at ambient temperatures 10, 25 or 40 degrees C. The brain seems to be
      warmer than the body only at the rectal temperature 36-37 degrees C. At a higher
      temperature the brain becomes cooler than the body.

PMID- 7530093
TI  - [The effect of insufficient nutrition during the suckling of rats on their growth
      and digestion].
AB  - The average weight of the bodies and the small intestine brush was 30% less in
      the malnourished 21-day old rats as compared with the control. The weight of the
      pancreas was 18% less. A decrease in the hydrolytic strength of the enzyme pools
      followed the changes in enzymatic activity during the primary and the last
      hydrolysis of food.

PMID- 7530096
TI  - AIDS and the family: World AIDS Day.

PMID- 7530097
TI  - Wide complex bigeminy: unusual presentation of an atriofascicular fiber.
AB  - Ventricular bigeminy in children is regarded as a benign arrhythmia in the
      absence of coexisting heart disease. We present the case of a patient with an
      atriofascicular fiber that electrocardiographically presented as wide complex
      bigeminy and wide complex tachycardia. At electrophysiologic study, the mechanism
      for the wide complex extrasystoles was reentry within the atriofascicular fiber
      or at its atrial insertion. Retrograde conduction within the fiber was also
      demonstrated under the influence of verapamil and ventricular extrastimulus
      testing. We conclude that conduction through an atriofascicular fiber should be
      included in the differential diagnosis of wide complex bigeminy having left
      bundle branch block morphology.

PMID- 7530098
TI  - The Hamburger Institute.

PMID- 7530095
TI  - AIDS and HIV-1 infection worldwide.

PMID- 7530099
TI  - Excimer laser in situ keratomileusis and photorefractive keratectomy for
      correction of high myopia.
AB  - BACKGROUND: The purpose of this research was to study the visual outcome of
      excimer laser photorefractive keratectomy and laser in situ keratomileusis
      (LASIK) for the correction of moderate and high myopia. METHODS: Twenty partially
      sighted eyes of 20 patients were divided into two groups, LASIK and
      photorefractive keratectomy. Ten eyes underwent LASIK and the other 10
      photorefractive keratectomy. Follow up was at 1, 3, 6, and 12 months. The LASIK
      technique included a nasally based, 150 microns thick, 8.0 x 9.0 mm diameter,
      truncated, disc-shaped corneal flap created with a microkeratome; and the
      ablation of the stroma with a 193-nanometer ArF excimer laser. The flap was
      returned to its original position and held in place by apposition. The
      photorefractive keratectomy technique included mechanical removal of the
      epithelium and ablation of the stroma with a 193-nanometer ArF excimer laser.
      RESULTS: LASIK series: One eye had a ruptured globe during the second
      postoperative month and was excluded from the study. The preoperative spherical
      equivalent refraction ranged from -10.62 to -25.87 diopters (D). The attempted
      correction ranged from -8.00 to -16.00 D. Postoperative refraction and corneal
      topography stabilized between 4 and 12 weeks. Spectacle-corrected visual acuity
      was within 1 Snellen line of preoperative in all eyes. The refraction in six eyes
      (66.6%) was within +/- 1.00 D of the intended correction, and in eight eyes was
      within +/- 2.00 D (88.8%) at 12 months. The mean attempted correction (11.40 +/-
      2.60 D) was close to the mean achieved correction at 12 months (11.96 +/- 3.10
      D). The mean postoperative refractive astigmatism (1.50 +/- 0.97; range, 0.25 to
      3.50 D) was close to the preoperative astigmatism (1.70 +/- 1.15; range, 0 to
      3.75 D). Endothelial cell density at 12 months showed an average 8.67% of cell
      loss. All eyes showed a clear interface. Photorefractive keratectomy series: The
      preoperative spherical equivalent refraction ranged from -10.75 to -23.12 D. The
      attempted correction ranged from -8.80 to -17.60 D. Postoperative refraction
      showed regression throughout the follow-up period, and corneal topography did not
      stabilize. Spectacle-corrected visual acuity was within 1 Snellen line in eight
      eyes. Two eyes lost 2 and 3 Snellen lines. One eye was within +/- 1.00 D, and
      three eyes (30%) were within +/- 2.00 D of the intended correction at 12 months.
      The achieved correction mean (7.17 +/- 5.29 D) was 61% of the attempted mean
      (11.72 +/- 2.81 D) at 12 months. The postoperative refractive astigmatism (1.80
      +/- 0.95; range, 0.50 to 4.00 D) was very close to the preoperative (1.90 +/-
      1.33; range, 0 to 5.00 D). Endothelial cell density showed an average of 10.56%
      cell loss at 12 months. The mean haze at 12 months was 1.2 (0 to 4 scale).
      CONCLUSION: LASIK, although more complicated because of the use of a
      microkeratome, was more effective than photorefractive keratectomy in higher
      myopes. LASIK created less corneal haze. The refraction was more stable with
      LASIK in the correction of high myopia. Its predictability was three times that
      of PRK.

PMID- 7530094
TI  - Protecting health care workers and patients from hepatitis B.

PMID- 7530100
TI  - Noncontact laser photothermal keratoplasty. I: Biophysical principles and laser
      beam delivery system.
AB  - BACKGROUND: Thermal shrinkage of stromal collagen is known to produce changes in
      the corneal curvature. We designed a novel, noncontact laser beam delivery system
      to perform laser photothermal keratoplasty. MATERIALS AND METHODS: The instrument
      consisted of a pulsed holmium:YAG laser (2.10-micrometer wavelength, 250
      microsecond pulse width, 5-hertz repetition rate) coupled via a monofilament
      fiber to a common slit-lamp microscope equipped with a polyprism, an adjustable
      mask, and a projection lens. The system projected an 8-spot annular pattern of
      infrared laser energy on the cornea to achieve a thermal profile within the
      stroma and to attain controlled, predictable collagen shrinkage. The system
      produced treatment patterns of 8 to 32 spots of 150 to 600 microns diameter in
      concentric rings, continuously adjustable between 3 and 7 mm. The versatility of
      the system in creating different treatment patterns was tested on thermal paper
      and human cadaver eyes. RESULTS: A uniform beam profile and different treatment
      patterns for myopia, hyperopia, and astigmatism were obtained. Myopic correction
      of 6.00 diopters was demonstrated on cadaver eyes. Corneal topography documented
      corneal flattening (> 6.00 D) with the following treatment parameters: each spot
      size on the cornea = 300 microns, radiant exposure of each spot = 18.0 J/cm2,
      number of pulses = 1, diameter of the treatment ring = 3 mm. CONCLUSIONS:
      Noncontact slit-lamp microscope laser delivery system for laser photothermal
      keratoplasty provides flexible and precise selection of laser treatment
      parameters. It may improve the efficacy of the procedure.

PMID- 7530101
TI  - Noncontact laser photothermal keratoplasty. II: Refractive effects and treatment
      parameters in cadaver eyes.
AB  - BACKGROUND: Noncontact laser photothermal keratoplasty may provide a new
      alternative for the treatment of myopia, hyperopia, and astigmatism. The purpose
      of this article is to study the refractive effect that laser photoablation
      keratoplasty is capable of producing on a normal human cadaver cornea, including
      the relationship between the keratometric changes and laser treatment parameters.
      METHODS: The human cadaver eyes were treated with a holmium laser (pulsed Ho:YAG,
      2.10 microns, 250 microseconds) coupled to a maskable, polyprismatic delivery
      system mounted on either an optical bench or a slit-lamp microscope. Using a
      topographic videokeratography system, we first investigated the refractive effect
      that noncontact laser photothermal keratoplasty would produce on a normal cadaver
      cornea. We then studied the keratometric changes produced by different radiant
      exposure levels at a fixed treatment pattern, as well as by different treatment
      patterns at a fixed radiant exposure level. Finally, we studied the possible
      therapeutic application of laser photothermal keratoplasty for correcting high
      postoperative astigmatism on a cadaver eye model. RESULTS: For the single-pulse 3
      millimeter ring of eight-spot treatment, the keratometric power of the cornea
      initially increased with the radiant exposure and peaked at 26 J/cm2. The
      refractive effect was increased by projecting an additional set of eight spots
      equidistant between the first eight spots on the same diameter ring. Eighteen
      J/cm2 was the minimal radiant exposure required to produce consistent and
      predictable keratometric changes. The corneas were flattened using treatment
      patterns smaller than or equal to 3 mm in diameter and steepened using treatment
      patterns larger than or equal to 5 mm in diameter. A transition zone between 4
      and 5 mm was observed in which minimal and unpredictable keratometric changes of
      the central cornea occurred. The surgically-induced astigmatism (> 10.00 D) was
      corrected by progressive laser photothermal keratoplasty treatments. CONCLUSIONS:
      Laser photothermal keratoplasty can acutely steepen and flatten the cornea in
      human cadaver eyes.

PMID- 7530103
TI  - Astigmatism following photorefractive keratectomy for myopia.
AB  - BACKGROUND: Astigmatism following photorefractive keratectomy for myopia has been
      reported as stable as early as 2 to 3 months. The authors report 36 out of 60
      consecutive eyes with variations in the cylindrical component of their refraction
      at 6 months after laser treatment. METHOD: A standard photorefractive keratectomy
      was carried out on 60 consecutive eyes in 52 patients over a 7-month period. The
      manifest refraction of these eyes was followed for 6 months. RESULTS: Thirty-six
      eyes demonstrated a change in the cylindrical element of their refraction
      manifested as a change in cylinder power or axis, or both. The mean pretreatment
      cylinder power in the group that underwent a change in the cylindrical element
      was significantly higher than the mean of the group where this did not take
      place. The mean cylinder power change was 0.75 diopters (D) and in 9 eyes this
      change was 1.00 D or more. The corrected and uncorrected postoperative visual
      acuities were the same in the two groups. CONCLUSIONS: This observation implies
      meridional variability in the healing process of the anterior cornea following
      photorefractive keratectomy.

PMID- 7530102
TI  - Noncontact laser photothermal keratoplasty. III: Histological study in animal
      eyes.
AB  - BACKGROUND: Laser photothermal keratoplasty has been studied as a potential
      refractive procedure. The purpose of this study is to investigate the
      histological response to various laser treatments including geometrical patterns,
      radiant exposure levels, and pulse numbers. MATERIALS AND METHODS: A noncontact
      laser photothermal keratoplasty system was used in this study. Epithelial and
      endothelial response to the laser photothermal keratoplasty annulus treatment
      pattern were studied on an owl monkey model with a 5-millimeter annulus ring
      pattern, 8 J/cm2, 25 consecutive pulses at 1 Hz. Epithelial and endothelial
      response to the laser photothermal keratoplasty spot pattern were then studied
      and compared on cat and rabbit models for safety monitoring. One pulse and five
      consecutive pulses of eight different radiant exposures (5.00 J/cm2 to 18.01
      J/cm2) were applied on each cornea. A cadaver eye model was used to study the
      collagen shrinkage induced by the laser spot treatment following the same
      protocol as the cat and rabbit model. Finally, the biological healing response to
      the laser photothermal keratoplasty treatment with the optimal laser parameters
      obtained in our experiment was studied on the cat model. Five cats were treated
      by the laser photothermal keratoplasty procedure with eight spots on a 3
      millimeter ring, 15.6 J/cm2, and 1 pulse. RESULTS: Epithelial and endothelial
      damage were observed after annulus treatment on an owl monkey's cornea at 8
      J/cm2, 25 pulses, and after spot treatment on cat and rabbit corneas at 18.01
      J/cm2, five pulses. No endothelial damage was observed on cat corneas for the
      single pulse treatment at 18.01 J/cm2. For the tissue shrinkage study, no laser
      photothermal keratoplasty lesion could be detected for a radiant exposure setting
      below 10.26 J/cm2. Histological cross-sections showed that the five-pulse
      treatment reached the endothelial layer at a radiant exposure of 13.4 J/cm2,
      while no single pulse treatment reached the endothelium for the radiant exposure
      range (5 J/cm2 to 18 J/cm2) studied. The cat model showed that the laser-induced
      mechanical octagonal stress-lines by collagen shrinkage were maintained after 3
      months. The histological sections across the lesion showed a denser keratocyte
      population indicating scar formation. CONCLUSION: The volume of collagen
      shrinkage, its location, and its geometrical shape can be accurately and
      precisely controlled by a 2.10-micrometer Ho:YAG laser coupled to an optical
      delivery system.

PMID- 7530104
TI  - Retrospective comparison of simultaneous and non-simultaneous bilateral radial
      keratotomy.
AB  - PURPOSE: Many radial keratotomy surgeons advocate bilateral simultaneous surgery,
      in which there is an inherent, although rare, risk of bilateral sight-threatening
      complications such as microbial keratitis. This study was designed to evaluate
      the refractive outcomes of simultaneous and non-simultaneous radial keratotomy
      performed by a single surgeon. METHODS: We retrospectively compared the results
      of radial keratotomy performed simultaneously (both eyes operated on the same
      day, 20 patients) versus non-simultaneously (right and left eyes operated on
      different days, 71 patients) by a single surgeon. Both eyes had the same surgical
      procedure, including clear zone diameter and number of incisions. RESULTS: The
      refractive results of bilateral simultaneous and non-simultaneous surgery were
      largely equivalent for all parameters analyzed except one. The variability of the
      difference in postoperative refractive error between right and left eyes was less
      for those patients undergoing simultaneous surgery (p = .0008). CONCLUSION: Our
      data suggest that performing radial keratotomy as a bilateral simultaneous
      procedure increases the symmetry of the refractive effect. In view of recent
      reports of sight-threatening risks such as bilateral microbial keratitis
      following bilateral keratotomy, however, the potential risks and benefits of
      bilateral surgery should be carefully considered before operating on both eyes on
      the same day.

PMID- 7530106
TI  - Changes in refraction induced by change in intraocular lens position.
AB  - BACKGROUND: Intraocular lens (IOL) decentration and tilt may affect postoperative
      refractive errors through spherical aberration of the IOL. METHODS: Through a use
      of a ray-tracing program and by minimizing algorithm, we calculated theoretical
      refractive errors for various degrees of IOL decentration and tilt. We compared
      our results with those obtained by paraxial vergence calculations. RESULTS: IOL
      decentration and/or tilt shifted postoperative refractive errors toward myopia
      and astigmatism of oblique origin. For example, a 3-millimeter decentration of an
      IOL resulted in induction of approximately -2.00 diopters (D) sphere and +0.70 D
      cylinder. IOL tilt affected refractive errors to a lesser degree. The change in
      refractive error caused by a combination of IOL decentration and tilt depended on
      the relationship between the geometrical axes of decentration and tilt. In the
      case of the least favorable combination of 12 degrees of tilt and 3 mm of
      decentration, it can reach -7.00 D sphere and +4.00 D cylinder. CONCLUSIONS: IOL
      decentration and/or tilt increase myopia and astigmatism. They are negligible for
      small decentrations, but could be sources of substantial postoperative refractive
      errors if the decentration or tile is large.

PMID- 7530105
TI  - Accommodation of an endocapsular silicone lens (Phaco-Ersatz) in the aging rhesus
      monkey.
AB  - BACKGROUND: After accommodative changes of endocapsular silicone lenses in
      presenile nonhuman primates had been confirmed by several authors, this pilot
      study was designed to evaluate the ability of an artificial lens to restore
      accommodation in the senile eye of a rhesus monkey that had previously lost most
      of its accommodative capability. METHODS: An injectable silicone lens was
      implanted in one eye of six rhesus monkeys who were older than 17 years.
      Accommodation was documented as the amount of decrease of anterior chamber depth
      after pilocarpine stimulation. RESULTS: Four months after surgery, the decrease
      of anterior chamber depth was higher in the operated eye with the silicone
      intraocular lens in the two monkeys who had marked presbyopic changes in the
      natural lens. One monkey was kept for more than 4 years, retaining a decrease of
      at least 0.5 mm with the silicone lens, whereas the natural lens failed to show
      any accommodative change. CONCLUSIONS: These findings support recent reports that
      presbyopia is primarily a consequence of lenticular aging rather than ciliary
      muscle factors. A pliable injected lens may therefore have the potential to
      restore accommodation in the senile primate eye.

PMID- 7530107
TI  - Suturing a posterior chamber intraocular lens to the iris through limbal
      incisions: results in 30 eyes.
AB  - BACKGROUND: I have previously reported a new technique of suture fixation of a
      posterior chamber intraocular lens (IOL) to the iris through a limbal incision in
      the absence of a posterior lens capsule. This study evaluated the results of that
      technique as an alternative to anterior chamber lens implantation or suturing of
      a posterior chamber lens through the ciliary sulcus and sclera. METHODS: The
      clinical records of 30 consecutive eyes that underwent this procedure between
      September 1987 and February 1991 were studied retrospectively. Four sutures were
      attached to four holes in the optic of a posterior chamber IOL. Two sutures on
      straight needles were passed through a superior limbal wound, to the pupil,
      reaching the inferior iris to be tied onto this iris. The two upper sutures on
      curved needles were passed through the pupil and going to the superior iris and
      then tied. RESULTS: An anterior vitrectomy was done in the pupil in 18 (60%)
      eyes. The mean postoperative follow-up time was 40 months (range, 24 to 66
      months). Nineteen eyes (63%) had visual acuities of 20/40 or better; and 10 eyes
      (33%) had visual acuities between 20/50 and 20/80. The remaining eye had
      persistent cystoid macular edema, proven by fluorescein angiography, with 20/100
      visual acuity. No serious anterior segment complications occurred. There was mild
      pigment dispersion on the IOL in four eyes. Four eyes needed timolol drops to
      lower the intraocular pressure. CONCLUSIONS: This technique offers a viable
      alternative to transscleral fixation of a posterior chamber IOL via a limbal
      approach.

PMID- 7530108
TI  - Theoretical and clinical effect of preoperative corneal curvature on excimer
      laser photorefractive keratectomy for myopia.
AB  - BACKGROUND: Individual clinical and optical variables may influence the effect of
      excimer laser photorefractive keratectomy. A theoretical model to describe the
      influence of initial corneal power, astigmatism, and topography on the expected
      results of photorefractive keratectomy would be useful in identifying those
      variables that may ultimately improve the predictability of the procedure.
      METHODS: Using a mathematical analysis based on the change in sagittal depth of
      the central ablation zone following photoablation, we predict the effect of
      initial corneal curvature on the ultimate outcome of a standardized
      photorefractive keratectomy. Refractive results from the Phase III US Food & Drug
      Administration clinical trials of photorefractive keratectomy were analyzed to
      confirm these mathematical predictions. RESULTS: We find that the initial corneal
      power, theoretically, is not expected to significantly affect the refractive
      change that results from a given ablation. Similarly, the corneal astigmatism
      present before photorefractive keratectomy is expected to be only minimally
      altered by a spherical excimer laser treatment. Clinically, there is no
      detectable difference in predictability of the procedure amongst groups
      stratified by initial mean keratometric power. CONCLUSIONS: Our analysis provides
      a methodology to predict the optical effects of photorefractive keratectomy upon
      the cornea and may be applied to a variety of hypothetical clinical settings. The
      predicted lack of clinical association between initial corneal curvature and
      predictability of photorefractive keratectomy is confirmed.

PMID- 7530109
TI  - Myopic keratomileusis by excimer laser on a lathe.
AB  - BACKGROUND: We designed an excimer laser keratomileusis delivery system to
      increase the regularity of the refractive cut surface and allow greater precision
      in the level and shape of the ablated zone. METHODS: A parallel faced corneal
      disc was produced by microkeratectomy from six human eyes and surgical
      keratectomy in 12 beagle corneas. A 193-nanometer excimer laser that was used to
      project an oval beam onto the corneal disc was rotated on a flat surface to
      ensure overlapping of the ovally ablated areas between pulses. RESULTS: Electron
      microscopy of eye bank lenticules demonstrated a circular smooth regularly
      concave ablation zone. Histological examination of nine clear corneas confirmed
      thinning of the stroma without fibroblastic reaction and no epithelial
      hypertrophy. Mean preoperative corneal power of 43.15 +/- 2.18 decreased
      postoperatively to 33.61 +/- 2.34. CONCLUSIONS: The new technique of excimer
      laser keratomileusis has the advantage of a cut surface smoother and the clear
      zone is devoid of the stepwise concavity and irregularity seen in diaphragm based
      photoablation delivery systems.

PMID- 7530110
TI  - Cleaning of ophthalmic diamond scalpels.
AB  - BACKGROUND: To ensure optimal performance, it is imperative to properly maintain
      the condition of ophthalmic diamond scalpels. Refractive surgeons are often
      confronted with conflicting cleaning recommendations from manufacturers. The
      problem encountered is to maximize cleaning while minimizing trauma to the
      diamond to maintain its longevity. METHODS: The author describes a flexible
      graded approach to cleaning and maintaining diamond scalpels. The principle of
      this approach was the development of four successive levels of cleaning based on
      an increasing risk of trauma to the diamond: Level I--irrigation with distilled
      water, Level II--hydrogen peroxide or enzyme cleaning, Level III--ultrasonic and
      detergent cleaning, and Level IV--mechanical styrofoam block cleaning. The
      protocol was performed prospectively on 50 consecutive radial keratotomy cases,
      inspecting the blade microscopically after each cleaning step, and determining
      the level at which cleanliness of the blade was achieved. RESULTS: The
      effectiveness (clean/dirty) of each cleaning level was evaluated by the author
      and an experienced surgical assistant. The difficulty in accurately measuring the
      amount of debris and the force necessary to remove it, limited the judgments made
      to subjective observation. Only 2 of 50 blades were cleaned at Level I, while 41
      of 48 at Level III, and 7 of 7 at Level IV. CONCLUSIONS: A multi-leveled
      systematic process for cleaning maintenance appears most effective for maximal
      performance and longevity of diamond scalpels used for refractive keratotomy
      surgery.

PMID- 7530111
TI  - Role of topical corticosteroids and nonsteroidal antiinflammatory drugs in the
      etiology of stromal infiltrates after excimer photorefractive keratectomy.

PMID- 7530112
TI  - Potential pitfall of the duo-trak style diamond knife.

PMID- 7530114
TI  - Secretion of insulin-like growth factor binding protein-1 from individual
      hepatocytes.
AB  - The reverse hemolytic plaque assay (RHPA) uses complement-mediated red blood cell
      lysis to detect peptide secretion by individual cells. Initially, the RHPA was
      used to study the function of neurons and B lymphocytes. More recently, the RHPA
      has been adapted to measure hormone release from individual pituitary,
      parathyroid, luteal, and pancreatic islet cells. We have applied this technique
      to detect insulin-like growth factor binding protein-1 (IGFBP-1) secretion by a
      human hepatoma cell line (HepG2). We proposed that the technique of RHPA could be
      used to study peptide release from single hepatocytes in various defined
      conditions. Our goal was the study of the kinetics of IGFBP-1 secretion from
      hepatoma cells and rat hepatocytes and to determine the heterogeneity of the cell
      population regarding the secretion of IGFBP-1. To evaluate the optimal conditions
      of IGFBP-1 secretion by hepatoma cells and rat hepatocytes and to evaluate the
      influence of cell dispersion on hepatocyte's behavior, we evaluated three
      techniques of cell dispersion: trypsin digestion, collagenase digestion, and
      mechanical dispersion. We tested cell viability, determined the percentage of
      secreting cells versus non-secreting cells, and measured mean plaque area which
      is a function of the amount of IGFBP-1 secreted by an individual cell. We
      determined the optimal IGFBP-1 antibody dilution for the detection of secreted
      IGFBP-1 by hepatocytes, evaluated the initiation of IGFBP-1 secretion from
      cultured cells, and quantified time-dependent IGFBP-1 secretion. In addition to
      demonstrating the feasibility of measuring IGFBP-1 from a cultured cell line, we
      measured IGFBP-1 release from freshly dispersed rat hepatocytes.

PMID- 7530113
TI  - Transplantation of encapsulated bovine chromaffin cells in the sheep subarachnoid
      space: a preclinical study for the treatment of cancer pain.
AB  - Chromaffin cells have been shown to release a combination of pain-reducing
      neuroactive compounds including catecholamines and opioid peptides. The
      allogeneic transplantation of chromaffin cells in the subarachnoid space has been
      shown to alleviate pain in various rodent models and possibly in terminal cancer
      patients. Because of the shortage of human cadaver donor tissue, we are
      investigating the possibility of transplanting xenogeneic cells in polymer
      capsules. In this technique, cells are surrounded by a permselective synthetic
      membrane whose pores are suitably sized to allow diffusion of nutrients,
      neurotransmitters and growth factors, but restrict the diffusion of the large
      molecules of the immune system and prevent contact with immunocompetent cells.
      The encapsulation technique therefore allows transplantation of xenogeneic tissue
      between species as well as retrieval of transplanted cells. Previously we have
      reported that encapsulated bovine chromaffin cells survive and alleviate pain in
      various rodent models. The purpose of the present study was to assess the
      feasibility of implanting a human sized device in a large animal model. Adrenals
      from 5 calves were surgically removed; chromaffin cells were isolated from these
      glands using a collagenase-based digestion-filtration technique. Cells were
      loaded into acrylic-based tubular (5 cm long, 920 microns wide) permselective
      capsules attached to silicone tethers. The capsules were maintained in vitro for
      at least 7 days following the encapsulation procedure. Nicotine evoked release
      was analyzed in a defined subgroup from each batch. One capsule was then
      implanted using a guiding cannula system in the lumbar subarachnoid space of each
      sheep for 4 (n = 5) and 8 (n = 1) wk. All capsules were retrieved intact by
      gentle pulling on the silicone tether. Except for one capsule, the evoked
      catecholamine release of the retrieved capsules was in the same range as that of
      other capsules from the same cohort that had been maintained in vitro. All
      retrieved capsules were devoid of host cell reaction. Clusters of viable cells
      dispersed in an alginate immobilizing matrix were observed throughout all the
      implanted capsules. This study demonstrates the feasibility of transplanting
      functional encapsulated xenogeneic chromaffin cells into the cerebrospinal fluid
      of a large animal model using a capsule of appropriate dimensions for human
      implants. We believe that these results suggest the appropriateness of human
      clinical trials in patients suffering from refractory terminal cancer pain.

PMID- 7530115
TI  - 'Prostate-related symptoms' in Canadian men 50 years of age or older: prevalence
      and relationships among symptoms.
AB  - OBJECTIVES: To determine the prevalence of symptoms associated with benign
      prostatic hyperplasia (BPH) in Canadian men, and to establish whether the
      traditional separation of these symptoms into obstructive and irritative
      categories is valid. SUBJECTS AND METHODS: A probability sample of 508 Canadian
      men 50 years of age or older was surveyed by telephone. The survey questions and
      scoring system used were devised to allow estimation of symptom prevalence and
      were based on the frequency and severity of the symptoms. Using the data from
      respondents who had moderate to severe symptoms, a cluster analysis was utilized
      to analyse relationships among symptoms. RESULTS: The most prevalent symptoms
      were nocturia (63%), weak stream (61%) and urinary frequency (46%). Urgency was
      reported by 18%, a sense of incomplete bladder emptying by 23%, intermittency by
      18% and hesitancy by 13%. Using predefined cutoff scores, 23% of the respondents
      experienced moderate to severe symptoms associated with BPH; the prevalence of
      moderate to severe symptoms increased with age. The clusters were grouped on the
      basis of the symptoms driving them, with one cluster designated as 'moderates',
      two clusters designated as 'irritatives' and two designated as 'obstructives'.
      The moderates cluster was driven by respondents who had lower symptom scores
      evenly distributed across all symptoms. The irritatives and obstructives clusters
      were driven by respondents with higher scores for symptoms considered by
      convention to be irritative or obstructive in nature and, thus, were designated
      accordingly. Not all symptoms were discriminatory for irritative and obstructive
      symptom domains. CONCLUSIONS: A large percentage of Canadian men 50 years of age
      or older experience symptoms commonly associated with BPH. The theoretical
      concept of irritative and obstructive symptom domains was supported partially by
      the cluster analysis. A clear typology of men with BPH symptoms could prove
      useful if treatments were found to be more effective for certain types of BPH
      symptoms. Thus these observations warrant further investigation into the
      differential effects of management approaches for BPH symptoms according to
      symptom clusters.

PMID- 7530117
TI  - The Bristol prostate cancer pilot screening study--a 3-year follow-up.
AB  - OBJECTIVE: To undertake a follow-up study of 472 men who were screened 3 years
      previously, in general practice, for prostate cancer, and to investigate the
      efficacy and patient acceptability of a 3-year screening interval. SUBJECTS AND
      METHODS: Eligible men (n = 472) were sent postal invitations to attend their
      Health Centre in North Bristol. Serum prostate-specific antigen (PSA) was the
      initial screening test. Men with PSA > 4 ng/ml (Hybritech) were referred to the
      Department of Urology for digital rectal examination and transrectal ultrasound
      +/- biopsy. RESULTS: A total of 132 (28%) men were excluded because of
      intercurrent illness, death and migration. Two hundred of 340 (59%) men were re
      screened. Thirty-seven men had an elevated PSA and were referred as above.
      Seventeen men had prostatic biopsies, resulting in the diagnosis of six
      carcinomas; five were localized to the prostate and one was metastatic. In the
      latter patient, the PSA had risen from 2 to 120 ng/ml over 3 years. CONCLUSION:
      Serum PSA alone can be used as an acceptable repeat screening test to detect
      prostate cancer in general practice, but 3-year repeat screening will not always
      protect the individual against the interval development of metastatic disease.

PMID- 7530116
TI  - Urinary symptoms in the community: how bothersome are they?
AB  - OBJECTIVES: To measure the level of reported urinary symptoms presumed to be
      associated with benign prostatic hyperplasia (BPH) among men aged 40 years and
      over in the community, and to assess how bothersome these symptoms are perceived
      to be. SUBJECTS AND METHODS: All ambulant men aged 40 years and over who were
      registered in a general practice (703) were invited to attend the health centre
      to complete a questionnaire containing the Maine prostatectomy scale and the
      International Continence Society-BPH questionnaire, and to undergo uroflowmetry.
      RESULTS: The prevalence of symptomatic BPH (as defined by a numerical score > or
      = 11 on the Maine score, a urinary peak flow of < 15 ml/s, and failure to void >
      or = 150 ml on three separate occasions) was 284/1000 for men aged 40 years and
      over. This prevalence increased from 179/1000 in men aged 40-49 to 500/1000 in
      men aged 70 years and over. The most commonly reported symptoms were those
      typically associated with BPH (terminal dribble, hesitancy, intermittency,
      urgency). The symptoms that caused men the greatest degree of bother were
      frequency, nocturia and those causing incontinence or social embarrassment.
      CONCLUSION: The high prevalence of urinary symptoms assumed to be related to BPH
      in men in the community does not necessarily suggest that these men will require
      treatment. Common symptoms, typically associated with BPH, were tolerated.
      Further research is required to investigate the natural history of urinary
      symptoms, the relationships between symptoms and bladder outflow obstruction
      secondary to BPH, and to determine the most appropriate management for men in the
      community, ranging from 'watchful waiting' (monitoring without treatment) to
      medical or surgical treatment.

PMID- 7530118
TI  - Deaths and complications following prostatectomy in 1400 men in the northern
      region of England. Northern Regional Prostate Audit Group.
AB  - OBJECTIVE: To determine the degree of variation in mortality and major morbidity
      following transurethral resection of the prostate (TURP), and to assess intersite
      variation for mortality and morbidity over 12 sites within the Northern Region.
      Further, to determine whether the previously observed effects on morbidity of
      unit size, patient through-put and emergency admission were borne out in
      contemporary urological practice in the Northern Region. PATIENTS AND METHODS:
      For an 8 month period, 1 April 1991-31 November 1991, an independent audit of
      TURP was performed on 12 different hospital sites throughout the Northern Region.
      A constant data set was designed which was collected on each patient before and 3
      months after operation by two independent clinical co-ordinators who travelled to
      each of the sites. All case notes were reviewed at 3 months after operation by
      the co-ordinators using a standard proforma, rather than depending upon self
      reporting by medical staff. Data on factors potentially affecting mortality and
      morbidity were collected, including emergency admission, diagnosis of prostate
      cancer, American Society of Anesthesiologists' co-morbidity scores, and age and
      differences in throughput in the 12 sites. The effect of through-put or 'volume'
      on mortality and morbidity was assessed by comparing morbidity and the number of
      cases performed. RESULTS: The early mean death rate was 13 of 1396 patients
      (0.9%), with an inter-site variation ranging from 0% to 3.8%. A mean of 2.0% of
      men were returned to theatre after TURP, 2.4% of patients received a blood
      transfusion (> 2 units) after operation, and 8.0% of patients developed post
      operative sepsis; these complications varied sixfold, sevenfold and 17-fold
      across the different sites respectively. Those units performing < or = 100
      operations over the audit period (equivalent to < 150 operation per year) had a
      significantly increased rate of deaths and complications which was not related to
      population differences, though some low volume units had good results. Elderly
      men who were admitted as emergencies or with prostate cancer were particularly
      vulnerable to complications. CONCLUSIONS: The overall early mortality rate after
      TURP for benign prostatic hyperplasia across the Region compares well with other
      reported large series. The significant variation in morbidity rates found in this
      study suggests that careful attention needs to be paid by Urologists, Purchasers
      and Providers to morbidity rates after prostatectomy.

PMID- 7530119
TI  - Update evaluation of benign prostatic hyperplasia: when should we offer
      prostatectomy?
AB  - OBJECTIVE: To investigate correlations between traditional and urodynamic
      criteria in the evaluation of prostatism and to try to establish an update
      evaluation of patients with benign prostatic hyperplasia (BPH) with the aim of
      preventing unnecessary prostatectomies. PATIENTS AND METHODS: The series
      constituted 96 patients aged 43-86 years (mean 63.41 +/- 9.25) with prostatism
      and BPH. All were assessed by symptom analysis, digital rectal examination,
      residual urine determination, uroflowmetry and further multichannel urodynamic
      testing (medium fill cystometry, pressure flow study). RESULTS: Residual urine
      determination was not a reliable criterion for selection of patients for surgery.
      A striking statistically significant correlation was evident when symptomatology
      and the results from multichannel urodynamic study were compared. No correlation
      was found between irritative symptoms and detrusor instability. CONCLUSION: A
      significant proportion (23%) of the whole patient population was classified as a
      urodynamically unobstructed group to which we think prostatectomy should not be
      offered. We recommend that a pressure-flow study is performed in all patients
      with BPH with dominant irritative symptoms to identify those who are
      unobstructed.

PMID- 7530120
TI  - Pharmacological characterization of alpha 1-adrenoceptor subtypes in the human
      prostate: functional and binding studies.
AB  - OBJECTIVE: To characterize the alpha 1-adrenoceptor subtypes of the human
      benignly enlarged prostate using functional and binding studies. MATERIALS AND
      METHODS: Strips of prostatic tissue taken from nine patients with benign
      prostatic hypertrophy who were undergoing open prostatectomy were used in the
      study. RESULTS: The strips isolated from five prostates produced a large
      contraction in response to noradrenaline and phenylephrine but not to clonidine.
      The contractile response induced by noradrenaline was competitively antagonized
      by representative alpha 1-adrenoceptor antagonists (prazosin, WB4101, 5
      methylurapidil and HV723), the dissociation constants (pKB) being < 8.5. Pre
      treatment with chloroethylclonidine was without effect on the contractile
      response to noradrenaline. In saturation experiments with five prostates, [3H]
      prazosin bound to the prostate membranes with two distinct affinities (pKD = 9.95
      +/- 0.07 and 8.71 +/- 0.04, Bmax = 151 +/- 8 and 138 +/- 3 fmol/mg protein,
      respectively). Unlabelled prazosin and WB4101 biphasically displaced the binding
      of 200 pM [3H]-prazosin; the resulting high and low pKI values for each of the
      antagonists were consistent with the two pKD values obtained for [3H]-prazosin in
      the saturation experiments. 5-Methylurapidil and HV723 displaced the [3H]
      prazosin binding monophasically with an affinity (pKI) close to 8.5. CONCLUSIONS:
      These results suggest the presence of at least two distinct alpha 1-adrenoceptor
      subtypes (presumably an alpha 1C subtype with a high affinity for prazosin and
      WB4101, and a putative alpha 1L subtype with a low affinity for the antagonists)
      in the human prostate, in which the latter subtype may be predominantly involved
      in the contractile response to noradrenaline.

PMID- 7530122
TI  - Alpha 1-adrenoceptor subtypes in the human prostate.
AB  - OBJECTIVE: To determine the subset of alpha 1-adrenoceptors mediating the
      functional abstraction of the prostate to noradrenaline. MATERIALS AND METHODS:
      Radioligand experiments were performed with membranes prepared from rat 1
      fibroblasts transfected with rat alpha 1a, hamster alpha 1b or bovine alpha 1c
      adrenoceptor cDNA. Human prostatic tissue obtained from transurethral resection
      of the prostate with full informed consent was submitted to functional in vitro
      muscle strip experiments. RESULTS: The binding experiments defined the potential
      subtype selectivity of various antagonists. Using this information, it was
      possible to define the functionally important alpha 1-adrenoceptor subtype in the
      human prostate. CONCLUSION: This work reports the results of the first functional
      characterization of the alpha 1c-adrenoceptor subtype. The most functionally
      important alpha 1-adrenoceptor type in the human prostate appears to be the alpha
      1c subtype. This finding may aid the development of prostate-selective
      adrenoceptor pharmacotherapy.

PMID- 7530123
TI  - The diagnostic value of colour Doppler flow in the peripheral zone of the
      prostate, with histological correlation.
AB  - OBJECTIVE: To study the discriminative value of the amount of colour flow on
      Doppler ultrasound within the peripheral zone of the prostate. PATIENTS AND
      METHODS: One-hundred and twenty three men were studied using a 7 MHz transrectal
      probe, and 274 guided biopsies were undertaken. With each biopsy histological
      outcome was correlated with the grade of colour flow on ultrasound hard copy
      images. Biopsies with inflammatory cell infiltration, but without carcinoma, were
      subgraded according to the degree of inflammatory cell infiltration; and these
      grades were correlated with the corresponding colour flow grade. RESULTS: Normal
      colour flow was seen with both normal and abnormal prostate biopsy. With
      increased colour flow the likelihood of abnormal tissue increases; the highest
      grade of colour flow was seen with either carcinoma or prostatitis (grade 0, 1, 2
      and 3 colour flow = 23%, 65%, 74% and 100% respectively of biopsies that were
      abnormal). In biopsies with inflammatory cell infiltration there was no linear
      relationship between the grades of colour flow and cellular infiltration (r =
      0.52, P > or = 0.05, Kendall rank correlation). The mean grade of cellular
      infiltration was significantly greater in samples with grade 3 colour flow
      compared with grades 0-2. CONCLUSION: Grading of the amount of colour flow with
      Doppler ultrasound is of limited diagnostic discrimination, although with the
      greatest colour flow specificity for the diagnosis of abnormal prostate (either
      cancer or prostatitis) is very high. With prostatitis, markedly increased colour
      flow reflects the severity of inflammatory cellular reaction.

PMID- 7530124
TI  - Transrectal ultrasound versus magnetic resonance imaging in the estimation of
      prostatic volume.
AB  - OBJECTIVE: To establish which method of determining prostatic volume (transrectal
      ultrasound [TRUS] or magnetic resonance imaging [MRI]) and which calculation
      formula give the most exact and least variable results; to determine the size and
      the source of the variability: and to establish which method is the more
      sensitive to drug-induced changes in prostate volume. PATIENTS AND METHODS:
      Prostatic size was estimated by TRUS and MRI in 21 patients treated medically
      (either active treatment or placebo) for benign prostatic hyperplasia. Each
      patient was examined at baseline, and after 3 months and 6 months of treatment.
      Prostatic volume was calculated at every visit using different formulae proposed
      in the literature. RESULTS: With some of these formulae, including the classical
      ellipsoid formula, there was a strong correlation (r > 0.8) between TRUS and MRI
      volume estimates. For others the correlation was much weaker, suggesting
      unreliability. MRI gave a significantly larger volume than TRUS because of larger
      values for the cephalocaudal and anteroposterior diameters. For patients on
      placebo the visit-to-visit variability of the prostate volume was 10-12% of the
      mean volume, whether calculated by TRUS or MRI. Part of this variability was
      apparently due to natural variation of prostate size. CONCLUSION: The classical
      ellipsoid formula is adequate for determining prostate volume. MRI and TRUS give
      different volumes. Visit-to-visit variability is similar for both methods and is
      partly due to real, natural variation. MRI is better able than TRUS to detect
      drug-induced changes in prostate volume.

PMID- 7530125
TI  - Three-dimensional imaging of the prostatic urethra--an exciting new tool.
AB  - OBJECTIVE: To evaluate the technique of three-dimensional (3-D) ultrasound
      imaging of the urethra and its application in both research and clinical
      practice. PATIENTS AND TECHNIQUE: The study involved 23 patients: 10 with benign
      prostatic hyperplasia, four with urethral strictures, three post-insertion of
      prostatic stents, one with bladder neck dyssynergia, three post-transurethral
      resection of the prostate, and two with non-urological conditions. A transrectal
      ultrasound scan was initially performed to acquire a series of images of the
      urethra. These images were then reconstructed into a 3-D format. RESULTS: The 3-D
      image of the urethra could be rotated on screen and viewed from any angle. The
      image could also be sliced at any plane to reveal the sectional view. CONCLUSION:
      This new tool represents a major advance in imaging techniques and promises to
      provide new knowledge in understanding the hydrodynamics of the lower urinary
      tract. The precise geometry of the 3-D urethra will also help in the design of
      new stents.

PMID- 7530121
TI  - Long-term treatment of benign prostatic hyperplasia with alfuzosin: a 24-30 month
      survey. BPHALF Group.
AB  - OBJECTIVE: To address the long-term results of alfuzosin, an alpha 1-antagonist,
      in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A 6
      month, placebo-controlled study involving 518 patients was followed by two
      successive one-year, open extensions. Only centres who wished to continue the
      trial participated in the extensions; 131 patients entered the first extension,
      with 50 continuing into the second year extension. The results of the second year
      follow-up are presented here. RESULTS: Depending on their initial randomization
      to either the placebo or alfuzosin arm, patients were treated with alfuzosin for
      24 (n = 50) or 30 months (n = 22). The data collected on those 50 patients in
      comparison to baseline confirmed that the clinical efficacy observed in
      short/medium-term studies was maintained. A clinically significant improvement in
      urinary symptoms was observed; the Boyarsky score decreased from 8.7 (+/- 0.3) at
      baseline to 5.2 (+/- 0.3) at 24 months, with no deterioration in the objective
      parameters. In patients treated for 30 months (n = 22), symptomatic assessment
      and urodynamic parameters remained stable, indicating the sustained effectiveness
      of therapy. No serious or unexpected side-effect related to long-term exposure to
      alfuzosin was observed. No complications associated with BPH occurred. Two
      patients (4%) reported dizziness, neither of whom withdrew from the study. In
      this population, where 40% of patients were receiving concomitant cardiovascular
      therapy, no clinically significant change in standing systolic blood pressure,
      diastolic blood pressure or heart rate was apparent between baseline data and
      those at 24 months. CONCLUSION: These data demonstrate the usefulness of long
      term treatment with alfuzosin in patients with uncomplicated, moderate BPH.

PMID- 7530126
TI  - Modulated expression of human leucocyte antigen class I and class II determinants
      in hyperplastic and malignant human prostatic epithelium.
AB  - OBJECTIVES: To determine whether human prostatic carcinoma cells express Class I
      and/or Class II major histocompatibility complex (MHC) determinants and whether
      they might thus be immune-competent targets for cell-mediated cytotoxicity.
      MATERIALS AND METHODS: Immunohistochemistry, performed both before and after
      neuraminidase digestion, was employed to compare 13 benign prostatic hyperplasias
      with 42 primary and 44 metastatic prostatic carcinomas obtained from the United
      Kingdom and from the United States of America. Expression of beta 2-microglobulin
      was used as the marker of Class I and HLA-DR as the marker of Class II
      expression. RESULTS: Before desialylation, Class I MHC determinants were
      expressed in all of the benign hyperplasias, in 26% of primary carcinomas and in
      14% of lymph node metastases. Cells expressing Class II determinants were
      identified in 69% of benign hyperplasias and in 2% of primary carcinomas, but in
      none of the lymph node metastases. After desialylation. Class I determinants were
      expressed in 100% of benign hyperplasias. 59% of primary carcinomas and 34% of
      the lymph node metastases. Class II determinants were expressed in 100% of benign
      hyperplasias, but only 19% of primary carcinomas and 5% of the lymph node
      metastases. While more than 50% of epithelial cells in each of the benign
      hyperplasias expressed MHCs, < 5% of the tumour cell populations in the positive
      malignant tissues (primary and metastatic) expressed MHCs, even after
      neuraminidase digestion. No correlation was found between expression of Class I
      or Class II MHC and Gleason morphological grade. CONCLUSIONS: Failure to express
      Class I and/or Class II MHC determinants is a common feature of the majority of
      human prostatic carcinoma cells. Absence of these recognition molecules may be
      associated with avoidance of immune-surveillance and contribute to the metastatic
      dissemination of this malignancy.

PMID- 7530127
TI  - Perineal versus retropubic radical prostatectomy for T1, T2 prostate cancer.
AB  - OBJECTIVE: To compare retrospectively the efficacy of radical perineal and
      retropubic prostatectomy in patients with T1, T2 cancer of the prostate. PATIENTS
      AND METHODS: From January 1991 to January 1993, 71 patients with T1, T2 carcinoma
      of the prostate aged 52-74 years underwent radical retropubic prostatectomy (36)
      or radical perineal prostatectomy (35); this was preceded by endosurgical
      lymphadenectomy. The two groups were identical with regard to age (64 vs 66
      years), clinical stage (T1a 17% vs 25%, T2 82% vs 74%), mean and median pre
      operative prostate-specific antigen (PSA) (20 vs 26, 11 vs 15 using the YANG
      polyclonal assay n < 2.5 ng/ml). Radical retropubic prostatectomy and radical
      perineal prostatectomy were performed using standard procedures. Specimens were
      inked and analysed; operative time, volume of blood transfusions, duration of
      hospital stay, peri-operative complications, sexual function, urinary continence
      and quality of the specimens were assessed retrospectively. RESULTS: Both groups
      were identical as far as operation time, hospital stay, complications (one rectal
      injury in each group), specimen weight and pathology were concerned. The
      proportions of organ-confined (54% in radical perineal prostatectomy group vs 55%
      in radical retropubic prostatectomy group) and margin-positive cancers (37% in
      radical perineal prostatectomy group vs 39% in radical retropubic prostatectomy
      group) were identical. The volume of blood transfusion was significantly less in
      the radical perineal prostatectomy group: 54% required transfusion compared with
      100% in the radical retropubic prostatectomy group), 7% of radical perineal
      prostatectomy patients received homologous transfusion vs 38% of the radical
      retropubic prostatectomy patients; 11 and 3% of the patients were potent 3-6
      months after surgery. Two anastomotic strictures developed after radical
      retropubic prostatectomy and none after the radical perineal prostatectomy.
      Continence was achieved at 3 months in 71% of the radical perineal prostatectomy
      group and in 82% of the radical retropubic prostatectomy group; by 6 months 88%
      of the patients were dry in both groups. CONCLUSION: When nodal status has been
      assessed by lymph node dissection (open or endosurgical), radical perineal
      prostatectomy is a reasonable, minimally invasive alternative to radical
      retropubic prostatectomy provided that impotence and a slower return to full
      continence are accepted.

PMID- 7530128
TI  - Experience with neoadjuvant diethylstilboestrol and radical prostatectomy in
      patients with locally advanced prostate cancer.
AB  - OBJECTIVE: To report our experience with neoadjuvant endocrine therapy and
      radical retropubic prostatectomy (RRP) in patients with locally advanced prostate
      cancer. PATIENTS AND METHODS: Fifty-five patients with prostatic adenocarcinoma
      (18 clinical stage B2/3, 27 clinical stage C, and 10 clinical stage D0) were
      treated with diethylstilboestrol (DES) 3 mg/d (median time 12 weeks, range 5-36)
      followed by pelvic lymph node dissection and planned RRP. Clinical response was
      monitored bi-weekly with serum prostate-specific antigen (PSA), serum acid
      phosphatase and digital rectal examination. RESULTS: The median pre-treatment
      serum PSA was 20.4 ng/ml (range 1.2-620). The median post-treatment, pre
      operative serum PSA was 0.4 ng/ml. Twenty-seven (49%), 41 (75%) and 54 (98%)
      patients had serum PSA levels that were undetectable, < 1.0 ng/ml and < 4.0 ng/ml
      respectively. In 15 patients, transrectal ultrasound measurement of prostatic
      volume changes was performed, and all demonstrated prostate volume reduction
      (median reduction 35%, range 18-45). All 55 patients underwent pelvic
      lymphadenectomy, with 47 (85%) undergoing RRP. Of the eight patients not
      undergoing RRP, three had negative lymph nodes but prostate resection was not
      deemed feasible and five had nodal metastases as determined by frozen section
      analysis. Final pathological stage revealed the following distribution: organ
      confined tumours, 18 (33%); capsular perforation with negative surgical margins,
      seminal vesicles and lymph nodes, seven (13%); seminal vesicle and/or margin
      involvement with negative lymph nodes, 18 (33%); lymph node metastases, 12 (22%).
      Neither pre-therapy serum PSA nor serum PSA response was predictive of final
      pathological stage. With a median follow-up interval of 26 months (range 12-49),
      21 patients (38%) have undetectable serum PSA without adjuvant therapy.
      CONCLUSIONS: Our results indicate that despite clinical evidence suggestive of
      downstaging, the majority of patients with locally advanced prostatic carcinoma
      managed with neoadjuvant DES and RRP continue to have pathological evidence of
      extraprostatic carcinoma.

PMID- 7530130
TI  - PSA/prostate volume ratio.

PMID- 7530129
TI  - Role of radiation therapy in the treatment of carcinoma of the penis.
AB  - OBJECTIVE: To study the effectiveness of radiation therapy (RT) for the primary
      tumour and for groin node and distant metastases in patients with squamous cell
      carcinoma of the penis. SUBJECTS AND METHODS: Between January 1959 and June 1988,
      156 patients with negative lymph nodes in the groin underwent RT of the primary
      tumour. RT was also administered to 120 patients with lymph node involvement in
      the groin and to nine with distant metastases. RESULTS: Local control of the
      primary tumour was achieved in 65% of patients with RT alone and in another 33%
      with salvage surgery. Lymph node recurrence in the groin was seen in 11% of
      patients and the corrected 5-year disease-free survival was 87%. Pre-operative
      inguinal RT was useful in patients with mobile lymph nodes > or = 4 cm in size in
      the groin, with only 8% of such lymphadenectomy specimens showing perinodal
      infiltration and only 3% of such patients having post-operative groin
      recurrences. Pelvic and/or para-aortic RT was ineffective in patients with pelvic
      node metastases. Palliative RT resulted in amelioration of symptoms in 56% of
      patients with fixed lymph nodes in the groin, all five patients with painful bony
      metastases and one of two patients with cord compression and paraplegia.
      CONCLUSION: Radiation therapy is ideal for patients with T1 and T2 primary
      cancers of the penis. Pre-operative RT is useful for patients with mobile lymph
      nodes > or = 4 cm in size in the groin. RT provides effective palliation in
      patients with advanced regional disease and/or distant metastases.

PMID- 7530132
TI  - Methodological analysis of immunocytochemical screening for disseminated
      epithelial tumor cells in bone marrow.
AB  - The emerging clinical relevance of bone marrow micrometastasis has prompted
      several investigations, using a variety of immunocytochemical approaches. The
      present study was designed to evaluate some of the variables affecting the
      immunocytochemical detection of individual epithelial tumor cells in bone marrow.
      Using an alkaline phosphatase-antialkaline phosphatase staining technique, we
      evaluated bone marrow aspirates from 358 patients with primary carcinomas of the
      breast (n = 150), lung (n = 66), prostate (n = 42), or colorectum (n = 100).
      Individual tumor cells in cytological preparations were detected with monoclonal
      antibody (MAb) CK2 to the epithelial cytokeratin component 18 (CK18), which has
      been validated in extensive clinical studies. In addition, the utility of the
      broad-spectrum MAb A45-B/B3 was explored in this study. The high specificity of
      MAbs CK2 and A45-B/B3 was supported by analysis of bone marrow from 75
      noncarcinoma control patients and by double-marker analysis with MAbs to
      mesenchymal marker proteins (CD45 and vimentin). In contrast, MAbs E29 and HMFG1,
      directed to mucin-like epithelial membrane proteins, cross-reacted with
      hematopoietic cells in 26.7-42.7% of all samples tested. The majority of the 154
      positive samples (43.0%) from cancer patients displayed less than 10 CK18
      positive cells per 8 x 10(5) marrow cells analyzed. The detection rate, however,
      was affected by blood contamination of the aspirate, the number of aspirates
      analyzed, and the number of marrow cells screened per aspiration site.
      Comparative immunostaining of bone marrow specimens with MAbs CK2 and A45-B/B3
      indicated that downregulation of CK18 in micrometastatic carcinoma cells occurs
      in about 50% of the 172 samples analyzed, regardless of the primary tumor
      origin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530134
TI  - Persistent problems of neutropenia and thrombocytopenia with peripheral blood
      stem cell transplantation.
AB  - We describe potential problems that may limit the usefulness of peripheral blood
      stem cells (PBSC) to facilitate the delivery of multiple cycles of high-dose
      chemotherapy. These include (1) cumulative myelotoxicity and (2) recurrent
      episodes of febrile neutropenia and a requirement for frequent platelet
      transfusions as a result of the stubborn persistence of a minimum of 7-9 days of
      absolute neutropenia and even longer durations of severe thrombocytopenia,
      despite utilization of PBSC. However, some of these problems may be overcome by
      shortening the duration of administration of the high-dose regimen with
      subsequent earlier reinfusion of the stem cell product. The adverse consequences
      of severe neutropenia could be overcome by the development of prophylactic
      neutrophil transfusions. These concepts are discussed with presentation of some
      preliminary data.

PMID- 7530131
TI  - Quantification of angiogenesis as an independent predictor of prognosis in
      invasive bladder carcinomas.
AB  - OBJECTIVE: To evaluate angiogenesis as a prognostic marker of transitional cell
      carcinoma of the bladder and to assess its relationship to established variables
      for survival. MATERIALS AND METHODS: Forty-five tumours (two G2T2, seven G3T2 and
      36 G3T3) from 36 men and nine women with a mean age of 73 years (range 50-91),
      who had been followed-up for a median of 37 months (range 1-50), were examined.
      Vessels were immunohistochemically highlighted using an antibody to the platelet
      endothelial cell adhesion molecule, CD31. Microvessel density was quantified
      using a Chalkley point eyepiece graticule. RESULTS: Univariate analysis of
      survival showed stage, grade and vascular count were significant indicators of
      prognosis (P = 0.002, P = 0.007, P = 0.019 respectively). No relationship was
      observed between stage and grade and vascular count. In a Cox proportional hazard
      model, adjusted for age and stage, microvessel density not only remained a
      significant prognostic indicator (P = 0.026) but was as informative as stage in
      predicting overall survival. A high vascular count conferred a 2.5 increased risk
      of mortality. CONCLUSIONS: These findings suggest that assessment of angiogenesis
      by microvessel quantification is an independent predictor of survival in patients
      with invasive bladder carcinoma and might be useful in selecting those who would
      benefit from adjuvant therapy.

PMID- 7530133
TI  - Peripheral blood progenitor cell transplantation in 118 patients with
      hematological malignancies: analysis of factors affecting the rate of
      engraftment.
AB  - We retrospectively studied the factors affecting the rate of hematopoietic
      reconstitution (HR) in 118 patients with hematological malignancies who underwent
      peripheral blood progenitor cell (PBPC) transplantation at a single institution.
      The patients received a median number of 6.6 x 10(8) nucleated cells/kg
      corresponding to 9.5 x 10(4) (0.5-578) CFU-GM/kg and 6.8 x 10(6) (0.2-161) CD34
      positive cells/kg. The median number of days to reach 500 polymorphonuclear
      cells/mm3 and 50,000 platelets/mm3 was 12.5 (6-93) and 14.5 (6-440) days,
      respectively. No patient died from infection during the aplastic phase. By
      multivariate analysis, we found that the dose of CFU-GM infused was the only
      factor that significantly affects the HR rate (p < 0.0001). Moreover, patients
      with acute myelogenous leukemia or those transplanted after busulfan or total
      body irradiation conditioning regimens had a slower engraftment (p < 0.08). These
      results could lead to identifying patients who need growth factors
      posttransplantation and/or the reinfusion of "back-up" marrow together with PBPC.

PMID- 7530135
TI  - Idarubicin, intermediate-dose cytarabine, etoposide, and granulocyte-colony
      stimulating factor are able to recruit CD34+/HLA-DR- cells during early
      hematopoietic recovery in accelerated and chronic phases of chronic myeloid
      leukemia.
AB  - A group of 46 patients with chronic myelogenous leukemia (CML) [chronic phase
      (CP), 24 patients; accelerated phase (AP), 22 patients] ineligible for allogeneic
      bone marrow transplantation were given an intensive chemotherapy regimen
      consisting of idarubicin, intermediate-dose cytarabine, and etoposide. All
      patients had previously received interferon-alpha and only 2 had shown a partial
      cytogenetic response. During early recovery from chemotherapy-induced aplasia,
      peripheral blood progenitor cells (PBPC) were harvested by leukapheresis. All
      metaphases were found to be Philadelphia chromosome (Ph) negative in the
      collection from 17 of 46 (37%) patients [CP, 12 of 24 (50%); AP, 5 of 22 (23%)],
      and a decrease to less than 50% Ph-positive metaphases was seen in an additional
      6 (CP, 3 patients; AP, 3 patients). The percentage of patients showing complete
      Ph disappearance was 64% in those receiving this procedure within the first year
      of diagnosis. In vitro studies were performed to assess the behavior of the Ph
      negative PBPC. In clonogenic cultures they responded to stem cell factor and were
      able to grow as mixed colonies. Moreover, long-term culture initiating cells
      (LTCIC) were present in many Ph-negative collections but rarely in Ph-positive
      PBPC. In 4 females, clonality was studied by analyzing X chromosome inactivation
      and methylation patterns of the DXS255 locus with the probe M27 beta.
      Hematopoiesis was polyclonal in all 4 patients tested. Thus far, the Ph-negative
      collections have been used for autografting in 16 patients (CP, 11 patients; PA,
      5 patients) after conditioning with total-body irradiation, etoposide, and
      cyclophosphamide or idarubicin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530136
TI  - Functional characterization of antiadhesion molecules.
AB  - Cytotactin, cytotactin binding (CTB) proteoglycan, and several other
      extracellular matrix (ECM) proteins and proteoglycans are described as
      antiadhesion molecules because they inhibit cell spreading and attachment to
      normally permissive ECM proteins. For cytotactin and CTB proteoglycan, this
      effect appears to be due to the binding of these proteins to their cell-surface
      receptors, which initiates a transmembrane signal that inhibits cell spreading.
      In contrast, the binding of fibronectin or laminin to its cell-surface receptors
      promotes cell spreading. Cell behavior may be regulated in a variety of systems
      by the interplay between these two opposing signals. For example, eosinophils on
      laminin spreading, form numerous foci containing filamentous actin, and remain
      viable in culture. In contrast, eosinophils on a mixture of laminin and
      cytotactin do not spread or form foci containing filamentous actin and the
      maintenance of viability is inhibited. In another system designed to model the
      immune surveillance of tumors, monocytes migrate in response to tumor necrosis
      factor through a gel comprised of a mixture of basement membrane proteins
      (Matrigel). Migration is blocked if the gel is coated with cytotactin. This
      result is of particular significance because cytotactin is expressed at high
      levels in the stroma of adult breast tissue surrounding tumors but only at low
      levels in normal breast tissue. These observations suggest that inflammation and
      the immune surveillance of tumors are among the processes regulated by
      cytotactin.

PMID- 7530137
TI  - Can tenascin be redundant in cancer development?
AB  - Histological and biochemical analyses of tenascin in various human tumors have
      indicated that tenascin is expressed in various cancer stroma and increased in
      the serum, getting strong with advancement of its malignancy. Of interest, the
      prognostic analysis of breast and colon cancers revealed favorable survival and
      no lymphogenous metastasis in patients whose cancer expressed tenascin strongly.
      Injection of tenascin nonproducing A431 human epidermoid cancer cells into nude
      mice resulted in tenascin production by these cells, suggesting cancer cells can
      make tenascin if necessary. Thus, both carcinoma and adjacent stroma cells may
      produce tenascin to coordinate the microenvironment surrounding the cancer
      tissues. Several tenascin variants have been clearly demonstrated to date. With
      these findings in mind, we would propose that epithelial tenascin supports the
      carcinoma cell outgrowth, whereas stromal tenascin may block cancer invasion by
      covering the cancer nest. No obvious phenotype in tenascin gene knockout mice
      would indicate that tenascin is functionally redundant in developmental
      processes, yet it may well be very important in progression of cancer.

PMID- 7530138
TI  - Tenascin isoforms: possible targets for diagnosis and therapy of cancer and
      mechanisms regulating their expression.
AB  - Functionally different tenascin (TN) isoforms containing varying numbers of III
      homology repeats are generated by alternative splicing of a single TN primary
      transcript. It has recently been reported that the larger TN isoform is, in
      general, more expressed in neoplastic tissues than in the normal tissues from
      which the tumor originates. This is due, at least in breast lesions, to the high
      proliferative activity of stromal elements. In fact, TN splicing is cell-cycle
      dependent, thus offering a viable system to study the molecular mechanisms that
      regulate alternative splicing and suggesting that cell-cycle dependent
      modifications in the splicing pattern of primary transcripts (which very likely
      are not limited to the TN pre-mRNA) may also be a cell-cycle regulatory
      mechanism. Furthermore, the very high accumulation of the larger TN isoform in
      neoplasia allows wider diagnostic and therapeutic monoclonal antibodies specific
      for the larger TN isoforms be considered for a number of tumors.

PMID- 7530139
TI  - Tenascin in connective tissue development and pathogenesis.
AB  - The extracellular matrix glycoprotein, tenascin (tenascin-C) is selectively
      expressed at sites of tissue remodeling in developing and pathological connective
      tissues, including cartilage, bone, and dermis. Functional studies suggest that
      tenascin is important for chondrocyte differentiation and feather bud elongation.
      Tenascin is able to stimulate cell migration and proliferation in some cell types
      and its tissue distribution is often correlated with these processes. Tenascin is
      a poor adhesive substratum for cells, and its effects on cell behavior may be
      mediated by effects on cell shape. In normal adult connective tissues, tenascin
      is strongly expressed at sites of contact between elements of the musculoskeletal
      system, suggesting an additional role for tenascin in matrix organization.

PMID- 7530140
TI  - Functional role of cytotactin/tenascin in morphogenesis: a modest proposal.
AB  - The evidence for a functional role of cytotactin/tenascin (CT/TN) in several
      developmental processes with particular emphasis on those related to the nervous
      system are reviewed. CT/TN gene regulation, as well as the growing family of TN
      related genes, is briefly discussed. Finally, I will explore the possibility that
      gene disruption experiments may not provide a unique resolution of gene function
      that was initially predicted when it became possible to manipulate mammalian
      genes with relative ease. It may be necessary to reevaluate the idea that these
      knockout experiments provide a definitive answer to the question of the function
      of a gene product. Cautious interpretation should be exercised in view of the
      large number of variables that can operate during embryogenesis, the existence of
      compensatory mechanisms during regulative development, and the pleiotropy
      resulting from mutation or deletion of a single gene. The reader should consider
      this a modest proposal, not a dogmatic one.

PMID- 7530141
TI  - The tenascin gene family.
AB  - Tenascin is believed to be an important extracellular matrix protein involved in
      regulating numerous developmental processes, such as morphogenetic cell migration
      and organogenesis. This function was implied by its tissue distribution and
      regulated expression during embryogenesis. However, such an important function
      was questioned recently, since mice lacking a functional tenascin gene apparently
      developed normally. To us, this is not conclusive evidence that tenascin has no
      function, for we believe that the loss of tenascin could be compensated for.
      Since in several other cases compensation occurs by other members of a gene
      family, we started to investigate the family of tenascin-like genes and we review
      in this article the structures of the original tenascin/cytotactin (tenascin-C),
      restrictin/J-160/180 (tenascin-R), and the tenascin-like gene present in the
      major histocompatibility complex class III locus (tenascin-X). Furthermore, we
      present evidence for the likely existence of even more members of this tenascin
      family.

PMID- 7530142
TI  - The perplexing multifunctionality of janusin, a tenascin-related molecule.
AB  - The extracellular matrix glycoprotein janusin, closely related to tenascin in its
      repeated motifs of epidermal growth factor, fibronectin type III, and fibrinogen
      like domains, displays in vitro a broad spectrum of functional diversity.
      Synthesized by oligodendrocytes and subpopulations of neurons at late
      developmental stages in the rodent central nervous system, it can be adhesive or
      antiadhesive, depending on the neural cell type that interacts with it. It
      promotes neurite outgrowth of some neural cell types, when offered as a uniform
      culture substrate, but inhibits neurite outgrowth of other neuronal populations.
      When offered as a sharp substrate boundary in congruence with a permissive
      substrate, it acts as a barrier for neurite outgrowth. Like tenascin, it can
      modify the adhesive substrate properties of another extracellular matrix
      glycoprotein, fibronectin, whereby the smaller, 160 kD component of janusin
      exerts its effects by interaction with fibronectin and the 180 kD janusin
      component functionally modifies the fibronectin receptor via a disialoganglioside
      receptor. In neurons, the antiadhesive and neurite outgrowth inhibiting signal is
      mediated by the F3/11 immunoglobulin superfamily recognition molecule. In
      oligodendrocytes, yet another receptor for janusin mediates adhesion and process
      formation. A prerequisite for any intracellular response to occur is a transient
      lock-and-key recognition manifesting itself in short-term binding between the
      interacting partners. As for tenascin, the different functions exerted by janusin
      are likely to be encoded in the different domains of the janusin molecule, which
      can act on different receptors, whereby the receiving cell is able to interpret
      the cell surface trigger in different ways, depending on the particular cell type
      involved.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530143
TI  - Tenascin-contactin/F11 interactions: a clue for a developmental role?
AB  - To understand how the extracellular matrix glycoprotein tenascin modifies cell
      adhesion and neurite outgrowth, we sought to isolate cellular receptors for
      tenascin. So far, two completely different cell surface ligands for tenascin have
      been detected. This we achieved by affinity chromatography of tissue extracts and
      of isolated proteins over tenascin-Sepharose and by solid-phase assays using the
      individual proteins. The first receptor, the neuronal cell adhesion molecule
      contactin/F11, a member of the immunoglobulin superfamily, binds to tenascin via
      a site in the N-terminal immunoglobulin-like domains. The binding site is within
      the fibronectin type III homology region at the boundary of the alternatively
      spliced region of tenascin, requiring that fibronectin type III homology domains
      5 and 9 be adjacent, as they are in the 190 kD tenascin isoform. The close
      similarity in tertiary structure between type III domains and immunoglobulin-like
      repeats raises the possibility that we are observing a side-by-side interaction
      between the two molecules in a manner closely analogous to that between paired
      immunoglobulin domains. The second receptor is the heparan sulfate proteoglycan,
      glypican, which, similarly to contactin/F11, is anchored to the membrane via
      glycosylphosphatidylinositol. Glypican bound to a column of tenascin-Sepharose
      cannot be dissociated by chondroitin sulfate or dermatan sulfate, but elutes in a
      broad peak with a gradient of heparan sulfate and in a sharper peak with heparin.
      By means of fusion proteins, we have identified a potential binding site on the
      fifth fibronectin type III homology domain of tenascin. We are trying to define
      these sites more closely by means of site-directed mutagenesis. It will be
      interesting to see whether the interaction between tenascin and cell surface
      contactin/F11, and possibly cellular heparan sulfate proteoglycans, contributes
      to the prominent role played by tenascin in pattern formation during development
      of the nervous system. In a first step, we have examined the distribution of
      tenascin isoforms and contactin/F11 during retinal development by means of
      immunohistochemistry and in situ hybridization with tenascin isoform-specific
      probes. Tenascin isoforms 190/200 along with contactin/F11 are particularly
      prominent in the inner and outer plexiform layers of embryonic day 8 retina in
      the chick. This coordinate up-regulation was confirmed both by immunoblots and
      Northern blots of retinal extracts. A speculative model is presented to suggest
      how the unique hexabrachion may signal the cell via contactin/F11.

PMID- 7530145
TI  - Tenascin-C in peripheral nerve morphogenesis.
AB  - The extracellular matrix (ECM) molecule tenascin/cytotactin (TN-C) is expressed
      at a high level by satellite (glial precursor) cells in developing peripheral
      nerves of the chick embryo; synthesis of its mRNA peaks at the time period when
      axonal growth is maximal. When offered as a substrate in vitro, TN-C mediates
      neurite outgrowth by both motor and sensory neurons. The ability to grow neurites
      on TN-C is developmentally regulated: sensory neurons from 4-day chick embryos
      (the stage at which peripheral nerves start to develop) grow immediately and
      rapidly, whereas neurons from older embryos respond with a long delay. A TN-C
      domain responsible for this activity is located within the C-terminal (distal)
      portion of TN-C subunits. Integrin receptors seem to be involved on peripheral
      neurites because their growth on TN-C is completely blocked by antibodies to beta
      1 integrins. In striking contrast to neuronal processes, nerve satellite cells
      can attach to a TN-C substrate but are completely inhibited in their migratory
      activity. Artificial substrate borders between tenascin and fibronectin or
      laminin act as selective barriers that allow neurites to pass while holding up
      satellite cells. The repulsive action of TN-C on satellite cells is similar to
      that observed for other cell types and is likely to be mediated by additional TN
      C domains. In view of these data, it is surprising that mice seem to develop
      normally without a functional TN-C gene. TN-C is likely to be redundant, that is,
      its dual action on cell adhesion is shared by other molecules.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 7530144
TI  - Tenascin glycoproteins in developing neural tissues: only decoration?
AB  - Tenascin glycoproteins constitute a growing family of extracellular matrix
      molecules that are transiently expressed by astrocytes during the development of
      the central nervous system (CNS). In some areas, tenascin distribution is
      discrete and tenascin boundaries delineate emerging functional processing units,
      for example, in the somatosensory cortex. The intact adult CNS displays low
      levels of expression and up-regulation of tenascin after lesion or in glial
      tumors. In vitro studies using the purified glycoprotein, bacterially expressed
      tenascin fusion proteins, monoclonal antibodies, and defined cell culture models
      have established that tenascin glycoproteins possess cell-binding sites for
      neural cells, support neuronal migration and the formation of neurites. On the
      other hand, tenascin also embodies repulsive, inhibitory properties that could
      serve to conceal neuronal assemblies and to segregate emerging fiber tracts.
      These functional properties are encoded by distinct domains of the molecule and
      suggest that tenascin glycoproteins are involved in neural pattern formation and
      regeneration. This interpretation is discussed with reference to a recent report
      that the elimination of the tenascin gene does not cause obvious abnormalities of
      neural tissues.

PMID- 7530147
TI  - Cellular origins of tenascin in the developing nervous system.
AB  - We have used in situ hybridization and reverse transcriptase polymerase chain
      reaction (PCR) to study the origins of the extracellular matrix glycoprotein
      tenascin during the development of the central and peripheral nervous systems.
      Previous studies have shown that neural crest cells migrate along pathways that
      are lined with tenascin. In situ hybridization, PCR, and western blotting reveal
      that these cells themselves are a major source of tenascin both in vitro and in
      the embryo. Thus, tenascin is probably not acting as a guidance molecule but is
      more likely to be promoting neural crest cell motility in a more general way.
      Similarly, subpopulations of proliferating and migrating glia make tenascin in
      the developing central nervous system, as do the radial glia that are used as a
      substratum for migrating neuronal cell bodies. In the adult, tenascin continues
      to be expressed in the cerebellum by Golgi epithelial cells. This expression, as
      well as the expression of tenascin in connective tissue, indicates that this
      molecule may also be playing a role in regulating differentiation. Finally, the
      distribution of tenascin transcripts in the developing brain and spinal cord is
      similar to the distribution of mRNAs encoding receptors for platelet-derived
      growth factor-AA and basic fibroblast growth factor. In vitro studies indicate
      that both of these factors are potential regulators of tenascin expression.

PMID- 7530148
TI  - Evolution of the tenascin family--implications for function of the C-terminal
      fibrinogen-like domain.
AB  - The three members of the tenascin (TN) family, TN-C, TN-R, and TN-X, are
      apparently conserved in all vertebrates and therefore must have functions that
      contribute to survival. One specific domain of tenascins, the fibrinogen-like
      terminal knob, can be argued to have an essential function. Its position at the C
      terminus makes it most vulnerable to loss through mutation or deletion, and it
      should have been eliminated in evolution if there were no selective pressure to
      maintain it. The epidermal growth factor and fibronectin III domains probably
      play an important role as spacers, placing the terminal knob at the end of the
      tribrachion or hexabrachion arms. In addition to functioning as spacers, at least
      some of these domains may have additional functional interactions. The
      conservation of these domains in evolution is comparable to that of some growth
      factors, consistent with this possibility. A phylogenetic tree of all known
      fibrinogen-related domains, including those in tenascins, is presented.

PMID- 7530146
TI  - Tenascin protein and mRNA in the avian visual system: distribution and potential
      contribution to retinotectal development.
AB  - The large glycoprotein tenascin is one of the extracellular matrix proteins that
      is abundant in the developing nervous system. To determine its distribution and
      possible role in the ontogenty of the avian retinotectal system, the distribution
      of the protein, the expression of its mRNA, and the effect of the protein on
      growing retinal neurites in vitro was investigated. Immunocytochemistry
      demonstrated that relatively little tenascin was present in the optic fiber layer
      of the retina, the optic nerve and tract. Tenascin, however, was abundant in the
      stratum opticum of the tectum, the target of retinal axons in the brain. Whereas
      tenascin protein is found only in discrete portions and layers of the brain, in
      situ hybridization studies showed that tenascin mRNA was expressed throughout
      development by radial glial cells at the ventricular surfaces of the brain,
      distant from the tissue localization of the protein. Injection of antitenascin
      antiserum into the tectal ventricle disturbed the distribution of the protein in
      the tectum by binding tenascin closer to its origin at the ventricular border.
      This suggests that the localization of tenascin in the brain is not restricted to
      its site of synthesis, but is mediated by tenascin-binding proteins that are
      expressed in defined areas and layers in the brain. In vitro studies showed that
      tenascin did not promote neurite outgrowth of retinal axons. On the contrary, the
      addition of tenascin to retinal explants growing on collagen or on L1 slowed the
      growth rate of optic axons by as much as 50%. The inhibitory function in vitro
      suggests that this protein has a modulatory role in axonal growth in vivo. The
      absence of tenascin from the optic fiber layer of retina, optic nerve, and optic
      tract and its abundance in the tectum suggest that tenascin may function to slow
      the rapidly growing optic nerve fibers once they arrive at the tectum. The
      slowing of optic fiber outgrowth may then facilitate terminal arborization and
      synapse formation within the tectum. The abundant tenascin in synaptic layers may
      also serve to stabilize synapses once they have formed.

PMID- 7530151
TI  - Expression of CD44 splice variants during lymphocyte activation and tumor
      progression.
AB  - Recently, splice variants of CD44 have been described that confer metastatic
      potential to non-metastasizing rat pancreatic carcinoma and sarcoma cell lines.
      Using antibodies against variant CD44 (CD44v) sequences, we have examined the
      expression of variant CD44 glycoproteins on human lymphoid cells and tissues and
      in colorectal neoplasia. Lymphohematopoietic cells express low levels of CD44v
      glycoproteins. During the process of lymphocyte activation in vitro and in vivo,
      expression of CD44v glycoproteins is transiently upregulated. The reaction
      pattern of various antibodies indicates that these CD44 variants contain the
      domain encoded by exon v6, which is part of the variant that confers metastatic
      capability. In human colorectal neoplasia we observed overexpression of CD44
      splice variants in all invasive carcinomas. Already at early stages of colorectal
      tumor progression exon v5 epitopes were overexpressed. Tumor progression was
      strongly related to expression of CD44 isoforms containing exon v6 encoded
      domains. The findings establish CD44 variants as tumor progression markers in
      colorectal cancer.

PMID- 7530150
TI  - Combination chemotherapy with epirubicin, cisplatin and 5-fluorouracil for the
      palliation of advanced gastric and oesophageal adenocarcinoma.
AB  - The palliative efficacy of laser therapy with combination chemotherapy
      (cisplatin, epirubicin and continuous infusion of 5-fluorouracil) was assessed in
      34 patients with inoperable gastro-oesophageal cancer. Comparison was made with a
      group of 30 patients treated previously by laser alone. Twenty patients responded
      to chemotherapy. There was a significant improvement in dysphagia, as measured by
      a decreased laser requirement to maintain satisfactory swallowing. In this non
      randomized prospective phase II trial, palliation was attained and some responses
      were long-lasting (median duration of response 8.7 (range 2.3 to more than 29.2)
      months).

PMID- 7530149
TI  - Segment III cholangiojejunostomy for palliation of malignant hilar obstruction.
AB  - Between 1984 and 1992, 26 patients with obstructive jaundice due to malignancy at
      the liver hilum were treated by segment III Roux-en-Y cholangiojejunostomy.
      Twenty-two patients had hilar cholangiocarcinoma, one carcinoma of the
      gallbladder, one pancreatic carcinoma, one recurrent gastric carcinoma and one
      lymphoma. Seventeen patients had no complications in the postoperative period and
      six had complications; there were three postoperative deaths. Eighteen of the 23
      surviving patients experienced complete resolution of jaundice for at least 3
      months. Four developed recurrent jaundice and three had episodes of cholangitis
      before death. Segment III cholangiojejunostomy offers effective palliation for
      most patients with irresectable hilar malignancy.

PMID- 7530154
TI  - Adverse effects of low concentrations of dietary RNA addition on the growth, food
      intake and kidney weight of young chickens.
AB  - 1. The effects of 0, 10 and 50 g/kg of RNA in diets on the growth and food intake
      of chicks from 6 to 21 d of age were examined. Their effects on renal tissue were
      examined by light microscopy at the end of experiment. 2. Total food intake and
      growth decreased with the increase in dietary RNA content and kidney weight was
      significantly increased by 50 g/kg RNA addition. A significant increase in liver
      weight was also observed in chickens fed on the diet-supplemented with 10 g
      RNA/kg. 3. The enlarged kidney caused by dietary RNA contained many crystals
      which were composed mainly of calcium salts but did not contain purines. 4. It is
      concluded that relatively low dietary RNA concentrations decrease food intake and
      growth and cause enlarged kidneys which contains many crystals composed mainly of
      calcium salts.

PMID- 7530152
TI  - Current views on structure and function of endothelial adhesion molecules.

PMID- 7530153
TI  - The correlation between neuron counts and optical density of NADPH-diaphorase
      histochemistry in the rat striatum: a quantitative study.
AB  - NADPH diaphorase (NADPH-d) histochemistry is a useful technique for examining
      select neuronal populations in both experimental studies and human neuropathology
      and also provides a simple method to localize nitric oxide synthase in the
      central nervous system. However, no established method exists for detecting
      quantitative changes of NADPH-d histochemistry under different experimental
      conditions. To develop a quantitative procedure, we systematically examined the
      properties of NADPH-d histochemistry and then investigated the correlation
      between the number of NADPH-d positive cells and the optical density of NADPH-d
      histochemistry in the rat striatum. NADPH-d activity was sensitive to specific
      experimental conditions, such as incubation time, fixation, and high temperature.
      In the striatum NADPH-d activity of neuropil was more sensitive to these
      conditions than were the somata. The different staining patterns of NADPH-d
      between the neuropil of the striatum and white matter, such as the optic tract
      suggest neuropil staining in the striatum is not just unspecific background
      staining. Increasing incubation time only increased the optical density of NADPH
      d staining, in contrast, the number of NADPH-d positive cells counted was
      relatively consistent across incubation times. Therefore, little correlation
      existed between the optical density and cell number. These results indicate that
      when using NADPH-d histochemistry, the number of NADPH-d positive neurons is
      independent of the optical density of the staining, and these two parameters
      should be considered and treated separately when conducting quantitative analysis
      related to an experimental treatment.

PMID- 7530155
TI  - Quantitative effects of pelleting on performance, gastrointestinal tract and
      behaviour of meat-type chickens.
AB  - 1. In an attempt to quantify the effects of "degree" of pelleting, two
      experiments were conducted. Diets were prepared by mixing together a mash
      composed mainly of maize (experiment 1) or sorghum (experiment 2) with soft
      pellets, or soft pellets mixed with hard pellets. 2. The pelleting degrees (PDs)
      were as follows: 0 mash; 0.5 mixture of soft pellets and mash 1 to 1; 1 soft
      pellets pelleted once; 1.5 mixture of soft and hard pellets 1 to 1; 2 hard
      pellets pelleted twice. 3. In experiment 2, the weight and length of the
      digestive organs were determined as well as digestive enzyme activities. In both
      experiments, the behaviour recorded was eating, standing, sitting and drinking.
      4. Food intake and body weight gain were related to the degree of pelleting in a
      curvilinear manner. PD had a positive effect up to a peak (1 to 1.5 PD), after
      which its effect decreased. Food efficiency was not related to PD. In experiment
      1, food efficiency of PDs 1 to 2 were superior to PDs 0 to 0.5 and in experiment
      2, PDs 1.5 to 2 were superior to PD 0. 5. The relative weight of the gizzard was
      reduced by pelleting, whereas pelleting increased the relative weight of
      abdominal fat. The content of the crop was not affected by PD, whereas that of
      the proventriculus was lowest in the PD 2 group. Gizzard content was inversely
      related to PD. Pelleting reduced the length of the jejunum and ileum: which were
      shortened by about 15% with PDs 1 to 2, as compared to PD 0. The weight/length
      ratio of the jejunum and ileum tended to increase with increasing PD to a peak at
      PD 1.5, and to decrease thereafter. 6. Trypsin activity in the pancreas and
      amylase activity in the intestinal content were reduced by pelleting. 7. Chicks
      fed pelleted diets were less active: they 'sat' more and spent less time eating
      than their mash-fed counterparts.

PMID- 7530156
TI  - Two sites (23-30, 76-90) on rat P-selectin mediate thrombin activated platelet
      neutrophil interactions.
AB  - The lectin-like domain of P-selectin, an adhesive receptor (also known as PADGEM,
      GMP-140 or CD62) is implicated in platelet or endothelial cell interactions with
      leukocytes. The aim of this study was to characterize the lectin-like domain of
      rat P-selectin by the use of synthetic peptides. The lectin and EGF-like domains
      of rat P-selectin were cloned in our laboratory and shown to present very strong
      homologies to its human counterpart. Peptides corresponding with the lectin-like
      domain of P-selectin were tested for their ability to inhibit thrombin-activated
      platelets rosetting to neutrophils. Peptides 23-30 (A) and 76-90 (C), but not
      peptide 51-61 (B), inhibited thrombin activated rat platelets interactions with
      rat neutrophils (A = 33%, C = 46%, P < 0.05). Using a combination of peptides
      (A+B = 35%, P = 0.008 and A+C = 62%, P < 0.001), we observe different degrees of
      inhibition of platelets binding to neutrophils. The IC50 of peptides A+C was 0.11
      mM. LYP-20, an anti-human P-selectin monoclonal antibody, was also observed to
      inhibit thrombin-activated rat platelets binding to rat neutrophils in a very
      significant manner (57% of inhibition, P < 0.001). Moreover, heparin inhibited
      thrombin-stimulated platelet/neutrophils rosetting (36% of inhibition, P < 0.01).
      These results show the importance of two sites (23-30 and 76-90) on the lectin
      like domain of P-selectin in mediating platelet-neutrophil interactions in rats.
      Such peptides may be potent in vivo inhibitors of cell-cell interactions
      involving P-selectin.

PMID- 7530157
TI  - Canine mitochondrial myopathy associated with reduced mitochondrial mRNA and
      altered cytochrome c oxidase activities in fibroblasts and skeletal muscle.
AB  - Skeletal muscle and fibroblast biopsies obtained from a normal dog and an old
      English sheep dog with exertional myopathy and lactic acidosis were examined for
      mitochondrial enzyme activities and mitochondrially coded mRNAs. The fibroblast
      cultures of the affected dog showed reduced cytochrome c oxidase (COX) I+II mRNA
      content (25% of control) and COX enzyme activities (23% of control). The skeletal
      muscle of the affected dog was similarly affected and showed not only decreased
      COX I+II mRNA content, but also decreased ATPase6 mRNA level. Apart from COX
      enzyme activity (62% of control), the oligomycin sensitive ATPase and NADH
      Ferricyanide reductase activities were also reduced in the skeletal muscle of the
      affected dog (12-20% of control). These results suggest that a mitochondrial
      dysfunction may be the causative factor of the exertional metabolic myopathy with
      lactic acidosis in this affected old English sheep dog. These animals may serve
      as an excellent model for mitochondrial myopathies.

PMID- 7530158
TI  - Ethical reasoning concerning the feeding of severely demented patients: an
      international perspective.
AB  - Structured interviews were held with 149 registered nurses in seven countries in
      America, Asia, Australia and Europe concerning the feeding of severely demented
      patients who do not accept food. The most common reasons for nurses being willing
      to change their decision to feed or not to feed were an order from the medical
      head, a request from the patient's husband and/or the staff meeting. There was a
      connection between the willingness to feed and the ranking of ethical principles.
      Nurses who were most prone to feed the patient most often gave a high rank to the
      ethical principle of sanctity of life, while those who primarily chose not to
      feed the patient gave a high rank to the ethical principle of autonomy. All
      nurses stressed the ethical principle of beneficence.

PMID- 7530159
TI  - Competitive binding experiments reveal differential interactions for
      dihydropyridine calcium channel activators and antagonists at dihydropyridine
      receptors on mouse brain membranes.
AB  - The binding of the dihydropyridine (+/-)-202-791 and its corresponding calcium
      channel activating and calcium channel antagonist enantiomers ((+)-S-202-791 and
      (-)-R-202-791, respectively) to dihydropyridine receptors on mouse brain
      membranes was studied through competition for [3H]nitrendipine binding and 3H
      labelled (+/-)-BAY K8644 ((+/-)-[3H]BAY K8644). Direct binding studies with (+/-)
      [3H]BAY K8644 and [3H]nitrendipine revealed high affinity binding to a
      homogeneous set of dihydropyridine calcium channel activator and antagonist
      receptors on mouse brain membranes, (+/-)-[3H]BAY K8644 binding to approximately
      one half as many receptors as did [3H]nitrendipine. Competition binding studies
      revealed a significant discrimination of both high and low affinity receptors for
      (-)-R-202-791 and a homogeneous set of receptors for (+)-S-202-791 regardless of
      whether (+/-)-[3H]BAY K8644 or [3H]nitrendipine was the competing radioligand.
      Molar ratios (1:1, 5:1, 10:1) of (+)-S-202-792 to (-)-R-202-791 inhibited
      [3H]nitrendipine binding with displacement binding isotherms substantially
      different from those predicted on the basis of the binding properties of the
      individual enantiomers. These data suggest that dihydropyridine calcium channel
      antagonists and activators bind to different allosterically linked receptors or
      domains of the dihydropyridine protein associated with the voltage-dependent
      calcium channels. Furthermore, these results support the concept of multiple
      binding sites for dihydropyridine ligands.

PMID- 7530160
TI  - Oxytocin induces an inward current in pregnant rat myometrial cells.
AB  - The effects of oxytocin (OT) on holding current were studied in uterine smooth
      muscle cells freshly isolated from the longitudinal layer of 18-20 day pregnant
      rats, using the nystatin method of whole-cell voltage clamp. As we previously
      reported, the voltage-dependent Ca2+ current (L type) was partially inhibited by
      OT (about 30% inhibition at 1 microM). When the cells were held at the holding
      potential (HP) of -60 mV and the holding current was monitored, OT induced an
      inward current. The amplitude of this OT-induced current was 72 +/- 26 pA (n =
      27). When the cell was held at more positive potentials (HP 0 or +40 mV), the OT
      induced current reversed direction, becoming outward. This current usually was
      long lasting (74% of cells responding to OT); a transient current was observed in
      26% of the cells. In the absence of either Na+ or Ca2+ in the bath solution, OT
      induced an inward current (at HP -60 mV). However, the OT-induced current was
      absent when both of these ions were omitted from the bath. These results suggest
      that OT induces an inward current through receptor-activated nonselective cation
      channels. The resulting increase of intracellular Ca2+ may contribute to the
      inhibition of voltage-dependent Ca2+ current produced by OT. This OT-induced
      current may also play an important role for membrane depolarization and
      accompanying contraction produced by OT in pregnant rat myometrium.

PMID- 7530161
TI  - Lack of pain control a tragedy.

PMID- 7530162
TI  - Position of palliative care physicians.

PMID- 7530163
TI  - Detection of prostate cancer.

PMID- 7530164
TI  - Factors associated with location of death (home or hospital) of patients referred
      to a palliative care team.
AB  - OBJECTIVE: To identify factors associated with the location of death (home or
      hospital) of patients referred to a palliative care home support team. DESIGN:
      Retrospective case-control chart review. SETTING: Palliative care inpatient unit
      with a home support team in a large chronic care hospital. SUBJECTS: All 75
      patients receiving services from the home support team who died at home between
      June 1988 and January 1990 and 75 randomly selected patients receiving the same
      services who died in hospital. OUTCOME MEASURES: Place of death (home or
      hospital). RESULTS: Of the 267 patients referred to the palliative care home
      support team during the study period 75 (28.1%) died at home. Factors
      significantly associated with dying at home were the patient's preference for
      dying at home recorded at the time of the initial assessment (p < 0.001), a
      family member other than the spouse involved in the patient's care (p = 0.021)
      and the use of private shift nursing (p < 0.001). The patients who died in
      hospital were more likely than the other patients to have had no home visits from
      the palliative care team after the initial assessment (p = 0.04). The patient's
      preference for dying at home was not met if the caregiver could not cope or if
      symptoms were uncontrolled. The patient's preference for dying in hospital was
      not met if his or her condition deteriorated rapidly or if the patient died
      suddenly. CONCLUSIONS: Patients' preference as to place of death, level of
      caregiver support and entitlement to private shift nursing were significantly
      associated with patients' dying at home. The determination of these factors
      should be part of every palliative care assessment. Patients and their families
      should be informed about available home support services.

PMID- 7530166
TI  - Intraoperative microwave tissue coagulation as treatment for patients with
      nonresectable hepatocellular carcinoma.
AB  - BACKGROUND: The microwave tissue coagulator (2450 MHz) has been used clinically
      in the treatment of hepatocellular carcinoma (HCC) to transection of the liver
      parenchyma and has proven an excellent method for hemostasis. There are, however,
      few reports on the application of this coagulator to the induction of tumor
      necrosis. METHODS: Microwave tissue coagulation (MTC) was applied at laparotomy
      in eight patients with nonresectable multiple HCCs. All patients were treated
      with a combination of resection or intrahepato-arterial chemotherapy and MTC. A
      total of 222 bouts of MTC were applied to 21 tumors, the largest of which was 65
      mm in largest dimension. The monopolar needle electrode was inserted directly
      into the tumor and the procedure was repeated at approximately 5 mm intervals.
      RESULTS: Levels of alpha-fetoprotein in serum were found to have decreased in all
      patients one month after surgery with MTC. Contrast-enhanced computerized
      tomography (CT) showed the complete absence of blood flow in all tumors subjected
      to MTC. Needle biopsy one month after MTC confirmed tumor necrosis in all cases.
      All patients are alive at the time of this report, with the longest survival
      period being 24 months. In three of eight patients, new tumors were confirmed by
      angiographic CT at sites separate from the treated tumors. MTC resulted in fewer
      adverse effects on liver function and less extensive inflammatory reactions than
      liver resection. CONCLUSION: Intraoperative MTC appears to be an effective method
      for inducing local tumor necrosis, and may be of use in combination with
      palliative surgery for multiple HCC when radical liver resection is not feasible.

PMID- 7530167
TI  - Management of recurrent malignant pleural effusions. The complementary role talc
      pleurodesis and pleuroperitoneal shunting.
AB  - BACKGROUND: Recurrent pleural effusions in patients with advanced cancer is a
      common problem that causes significant morbidity and can negatively affect
      patients' quality of life for their remaining months. Several palliative
      treatment options are available. METHODS: The results of a 10-year experience
      with 180 patients referred for the surgical palliation of their condition were
      retrospectively reviewed. Their mean age was 60 years (range, 20-90 years). One
      hundred and thirty-four patients (74%) had been treated before referral with one
      or more of the following modalities: repeated needle thoracocentesis (87
      patients), tube thoracostomy (24 patients), chemical or biologic pleurodesis (22
      patients), and pleurectomy (1 patient). One hundred and seventeen patients
      demonstrated full lung expansion at thoracoscopy/mini-thoracotomy and underwent
      talc pleurodesis, whereas the other 63 patients had the "trapped lung syndrome"
      and required the insertion of a pleuroperitoneal shunt (Denver, Biomedical, Inc).
      RESULTS: There were no intraoperative deaths and the early death rate was 5.9%
      for the talc pleurodesis group and 3.2% for the group that received shunts. The
      mean hospital stay for the patients receiving talc and shunts was 7.3 days
      (range, 3-15 days) and 5.9 days (range, 2-12 days), respectively. Follow-up data
      were available in 60% of the patients and showed that effective palliation was
      achieved in more than 95% of patients in each group. There were eight patients
      (12%) with blocked shunts (five requiring replacement or renovation and three
      requiring removal and open drainage) at 1 week to 4 months after insertion. Two
      patients (one from each group) required one further episode of treatment by
      thoracocentesis. The median survival for the talc and shunt groups was 4.9 months
      (range, 1-36 months) and 5.4 months (range, 1-53 months). Patients with effusions
      because of secondary breast carcinoma or lymphomas survived the longest.
      CONCLUSION: In patients with malignant pleural effusions in whom pleurodesis is
      precluded by limited lung expansion, effective palliation can be achieved by
      pleuro-peritoneal shunt insertion.

PMID- 7530165
TI  - Factors complicating the diagnosis of depression in cerebrovascular disease, Part
      II--Neurological deficits and various assessment methods.
AB  - Neurological deficits associated with cerebrovascular disease such as aphasia,
      dementia, anosognosia and aprosodia may impair the ability to express or
      experience depressive symptoms. Identification of depression in the absence of
      verbal report on subjective mood state is a difficult task. The value of various
      diagnostic methods including depressive rating scales, standard psychiatric
      interviews and biological variables in the diagnosis of depression in
      cerebrovascular disease is considered. This review concludes by focusing on the
      deficiencies of existing approaches in the diagnostic assessment of depression in
      patients with severe communication and comprehension deficits and emphasizes the
      importance of devising a standard diagnostic method with less reliance on verbal
      responses.

PMID- 7530168
TI  - Advanced diffuse non-Hodgkin's lymphoma. Analysis of prognostic factors by the
      international index and by lactic dehydrogenase in an intergroup study.
AB  - BACKGROUND: Recent data have suggested that there are no differences among
      various anthracycline-based chemotherapy regimens [including cyclophosphamide,
      vincristine, methotrexate, and prednisone (CHOP), methotrexate, calcium
      leucovorin, bleomycin, doxorubicin, cyclophosphamide, and dexamethasone (m
      BACOD), methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and
      bleomycin (MACOP-B), and cyclophosphamide, doxorubicin, etoposide, prednisone,
      cytosine arabinoside, bleomycin, vincristine, methotrexate, and calcium
      leucovorin (PROMACE-cyta-BOM)] in patients with diffuse aggressive lymphomas.
      Because outcome appears to depend on certain prognostic factors, risk groups can
      be identified. Therefore, these prognostic factors were examined for their
      correlations with survival, time-to-treatment failure (TTF), and disease free
      survival (DFS) in a group of patients with diffuse aggressive non-Hodgkin's
      lymphoma who were treated on a single randomized trial with either CHOP or m
      BACOD. METHODS: From July 1984 to January 1988, 392 patients with diffuse large
      cell or diffuse mixed non-Hodgkin's lymphoma were enrolled in an Intergroup study
      and were randomly assigned to treatment with CHOP or m-BACOD chemotherapy. Of
      these, 325 were eligible for response, toxicity, and survival analysis, and the
      results were reported. The survival and TTF results now have been updated. The
      286 patients who had lactic dehydrogenase (LDH) data available at study entry
      were analyzed for prognostic features according to the International Index
      criteria and using Martingale Residuals for proportional hazards regression.
      RESULTS: There were no differences in survival, TTF, and disease free survival
      between groups of patients treated with either CHOP or m-BACOD. In addition,
      analysis using the International Index criteria confirmed that patients in the
      lower risk groups had better outcome than patients in the higher risk groups (5
      year survival was 56 and 58% for low and low/intermediate risk groups,
      respectively, and 37% and 31% for high/intermediate and high risk groups,
      respectively). There were, however, no differences in survival, disease free
      survival, or TTF within any risk group when treatment with CHOP or m-BACOD were
      compared. In addition, analysis using Martingale residuals for proportional
      hazards regression identified LDH level (> 3 x normal) as an important prognostic
      factor that was not captured by the International Index. Thus, 5-year survival
      was 57% if LDH was normal or below, 42% if LDH was 1-3 x normal, and 21% if LDH
      was > 3 x normal. CONCLUSION: In patients with advanced diffuse large cell or
      diffuse mixed non-Hodgkin's lymphoma, there are no differences in outcome that
      can be attributed to treatment with CHOP vs. m-BACOD; this holds for any
      prognostic group identified by the International Index. However, the level of LDH
      at time of study entry is an important prognostic factor that is predictive of
      survival and may help to identify candidates for future clinical trials.

PMID- 7530171
TI  - Intracellular calcium transients in potentiated contractions induced by multiple
      extrasystolic beats in isolated perfused rat hearts.
AB  - Mechanisms underlying contractile potentiation induced by multiple extrasystolic
      contractions (ESC) were evaluated with surface fluorometry in isolated perfused
      rat hearts loaded with Indo-1/AM. After baseline pacing with a 400 ms interval, 1
      25 ESC were interposed with a regular 160 ms interval followed by the
      postextrasystolic beat with a 400 ms interval. With an increase in the ESC
      number, left ventricular developed pressure and peak positive dP/dt increased in
      an exponential manner, reaching a plateau, that was the same for 3 extracellular
      Ca2+ ([Ca2+]o; 0.55 (n = 9), 1.25 (n = 11) and 2.75 mM (n = 7). Increased [Ca2+]o
      shifted this relationship left and upward, and with 2.75 mM [Ca2+]o developed
      pressure and dP/dt decreased after the maximum potentiation was obtained. The
      relationship between the ESC number and the amplitude of the Indo-1 fluorescence
      (F400/F510; an index of intracellular Ca2+ ([Ca2+]i)) was also exponential and
      was shifted left and upward by high [Ca2+]o; however, it lacked the declining
      phase. Thus, the relationship between the amplitude of F400/F510 and developed
      pressure or dP/dt consisted of a positively linear part until the maximum
      potentiation was obtained and a negatively linear part with a further increase in
      the amplitude of F400/F510. This observation suggests that although contractile
      potentiation is mediated by increased [Ca2+]i transients, the maximum response
      might be determined by the responsiveness of the sarcomere.

PMID- 7530169
TI  - Novel tumor-associated accessory molecules involved in the gamma/delta cytotoxic
      T-lymphocyte-Burkitt's lymphoma interaction.
AB  - BACKGROUND: Tumor specific cytotoxic T lymphocytes (CTL) recognize antigen via
      the T-cell receptor (TCR). In addition, recognition requires accessory molecules
      involved in adhesion and signal transduction. The authors previously have
      characterized an autologous, Burkitt's lymphoma specific CTL line that uses the
      gamma-delta TCR to recognize antigen in a nonclassical context. The current study
      was undertaken to identify novel accessory molecules involved in this unusual TCR
      tumor cell interaction. METHODS: A panel of monoclonal antibodies was generated
      against a Burkitt's lymphoma cell line and was screened for inhibition of
      autologous, tumor specific, cytolysis by a gamma-delta CTL line. Proteins
      identified by these monoclonal antibodies were further characterized by
      fluorescent-activated cell sorter analysis, Western blot and immunoprecipitation.
      RESULTS: Three known (CD5, CD43, and CD11a/CD18) and three novel (BAM-1, BAM-2,
      and BAM-3) cell surface molecules involved in the gamma-delta CTL-Burkitt's
      lymphoma interaction were identified and characterized. CONCLUSIONS: This study
      identifies and provides a preliminary characterization of three novel Burkitt's
      lymphoma-associated molecules involved in the gamma-delta CTL-tumor cell
      interaction and demonstrates that CD5, CD43, and CD11a/CD18 are involved in this
      interaction. It is likely that other unidentified accessory molecules are also
      involved in this and other effector cell-tumor interactions. Identification of
      such molecules may be useful in the design of new immunotherapeutic approaches.

PMID- 7530170
TI  - Treatment of low-grade non-Hodgkin's lymphoma with continuous infusion of low
      dose recombinant interleukin-2 in combination with the B-cell-specific monoclonal
      antibody CLB-CD19.
AB  - Seven patients with low-grade non-Hodgkin's lymphoma were treated with a
      combination of a murine monoclonal antibody directed against the B-cell-specific
      antigen CD19 (CLB-CD19), given twice weekly, and continuous infusion of low-dose
      recombinant interleukin-2 (rIL-2). We demonstrated stable serum CLB-CD19 levels
      throughout the 12 weeks of treatment, and homing of the antibody into the tumour
      sites. A variable degree of antigenic modulation was noted. Prolonged treatment
      resulted in a sustained increase in the number of natural killer cells in the
      circulation with enhanced cytotoxic capacity, including antibody-dependent
      cellular cytotoxicity. During the first weeks of treatment, T cell activation
      occurred in the majority of patients. Toxicity was related to the rIL-2 treatment
      and consisted of transient constitutional symptoms and a flu-like syndrome
      without organ dysfunction. A partial remission occurred in one patient, and in
      another patient who was primarily leukaemic a greater than 50% reduction of
      circulating B cells was noted. An antitumour effect occurred early during
      treatment and could not be related to rIL-2-induced modulation of natural killer
      cell or T lymphocyte activation.

PMID- 7530172
TI  - Natural and synthetic antifibrinolytics in adult cardiac surgery: efficacy,
      effectiveness and efficiency.
AB  - Epsilon-aminocaproic acid and tranexamic acid, two synthetic antifibrinolytics,
      and aprotinin, an antifibrinolytic derived from bovine lung, are used to reduce
      excessive bleeding and transfusion of homologous blood products (HBP) after
      cardiac surgery. This review analyzes the studies on the utilization of
      antifibrinolytics in adult cardiac surgery according to the epidemiological
      concepts of efficacy, effectiveness and efficiency. A majority of published
      studies confirm the efficacy of antifibrinolytics administered prophylactically
      to reduce postoperative bleeding and transfusion of HBP. More studies are needed,
      however, to compare antifibrinolytics and determine if any one is superior to the
      others. Despite their demonstrated efficacy, antifibrinolytics are only one of
      the options available to diminish the use of HBP. Other blood-saving techniques,
      surgical expertise, temperature during cardiopulmonary bypass and respect of
      established transfusion guidelines may modify the effectiveness of
      antifibrinolytics to the point where antifibrinolytics may not be necessary. At
      this time, insufficient data have been published to perform a cost vs benefit
      analysis of the use of antifibrinolytics. This complex analysis takes into
      account not only direct costs (cost of the drug and of blood products), but also
      the ensuing effects of treatment such as: length of stay in the operating room,
      in the intensive care unit and in the hospital; need for surgical re-exploration;
      treatment of transfusion or drug-related complications, etc. In particular, the
      risk of thrombotic complications associated with antifibrinolytics is the subject
      of an ongoing, unresolved controversy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530174
TI  - Estrogen promotes angiogenic activity in human umbilical vein endothelial cells
      in vitro and in a murine model.
AB  - BACKGROUND: Angiogenesis is a critical event in wound healing, tumor growth, and
      the inflammatory vasculitides. Since women have a higher incidence of many
      vasculitic diseases, we examined the effects of female sex steroids, particularly
      estradiol, on human umbilical vein endothelial cell (HUVEC) behavior in vitro and
      on angiogenesis in vivo. METHODS AND RESULTS: HUVECs were grown in estrogen-free
      medium before each assay. Exogenous 17 beta-estradiol (1 to 5 nmol/L) increased
      cell attachment to laminin, types I and IV collagen, and fibronectin, as well as
      to tissue culture plastic. After a confluent monolayer of cells was "wounded" by
      scraping, estradiol-treated (10(-8) mol/L) cells migrated into the wound three
      times faster than untreated cells. Cell proliferation on plastic and on laminin
      increased threefold to fivefold, respectively, in the presence of estradiol.
      Estradiol also enhanced the ability of HUVECs to organize into tubular networks
      when plated on a reconstituted basement membrane, Matrigel. Estradiol effects on
      both the "wounding" assay and tube formation were blocked by the specific
      estrogen receptor antagonist ICI 182,780. Ovariectomy markedly decreased in vivo
      vascularization of Matrigel plugs coinjected with basic fibroblast growth factor
      in mice. With estrogen replacement, angiogenesis was increased to the levels
      observed in nonovariectomized mice. CONCLUSIONS: These studies demonstrate that,
      in vitro and in vivo, estradiol enhances endothelial cell activities important in
      neovascularization and suggest a promoting influence of estrogens on
      angiogenesis.

PMID- 7530175
TI  - IGF-I treatment of adult patients with Laron syndrome: preliminary results.
AB  - OBJECTIVE: Laron syndrome is a genetic disease due to a defect in the GH receptor
      or in the post-receptor mechanism which leads to an inability to generate IGF-I.
      Biosynthetic IGF-I treatment given to dwarfed children with this syndrome,
      produced a significant acceleration of growth velocity and reduction in obesity.
      In view of the known metabolic disturbances in untreated adult patients, the
      present clinical trial was performed to define the usefulness of IGF-I treatment
      in LS adults. PATIENTS AND DESIGN: Five patients (1 male, 4 females) aged 28-40
      years were treated during 9 months by daily administration of IGF-I (120
      micrograms/kg), and followed for 6 months after its discontinuation. METHODS: At
      each visit, a complete physical examination was performed and blood was drawn for
      biochemical and hormone determinations. Twenty-four-hour urinary samples were
      collected at various intervals during treatment. Bone densitometry was performed
      before and after 6-9 months of therapy. RESULTS: The main findings were a
      reduction in subscapular skinfold thickness (from 27.5 +/- 1.4 (mean +/- SEM) to
      19.5 +/- 1.0 mm; P < 0.002), a decrease in total cholesterol (from 6.78 +/- 0.28
      (mean +/- SEM) to 5.80 +/- 0.36 mmol/l) and in LDL cholesterol (from 4.86 +/-
      0.23 to 3.76 +/- 0.35 mmol/l), an increase in creatinine clearance (from 71.2 +/-
      8.4 to 86.8 +/- 4.3 ml/min/1.73 m2, P < 0.04), an increase in phosphate
      reabsorption (from 0.89 +/- 0.06 to 1.14 +/- 0.06 mmol%; P < 0.02) leading to an
      increase in serum phosphate (from 1.08 +/- 0.06 to 1.27 +/- 0.03 mmol/l; P <
      0.03), a rise in alkaline phosphatase (from 80.8 +/- 5.0 to 100.7 +/- 7.0 U/l)
      and in procollagen I-PICP (from 44.2 +/- 4.0 to 171.0 +/- 19.2 micrograms/l; P <
      0.0001) and in procollagen III-PIIINP (from 2.68 +/- 0.45 to 10.10 +/- 1.4
      micrograms/l; P < 0.005). There was a transient retention of water, sodium and
      chloride. Pretreatment serum IGFBP-3 levels were low, but increased progressively
      during treatment. This permitted a reduction in the IGF-I dose. There were no
      adverse effects other than pain and slight erythema at the injection site during
      the first weeks of treatment. All the anthropometric and metabolic changes
      reversed upon discontinuation of IGF-I. CONCLUSIONS: IGF-I treatment is
      beneficial in adults, as well as in children, with resistance to GH.

PMID- 7530173
TI  - A phase I trial of concomitant chemoradiotherapy with cisplatin dose
      intensification and granulocyte-colony stimulating factor support for advanced
      malignancies of the chest.
AB  - Concomitant chemoradiotherapy with cisplatin and combination chemotherapy in the
      neoadjuvant setting have both shown promising results. PURPOSE: To identify a
      locally and systemically active concomitant chemoradiotherapy regimen
      incorporating high-dose cisplatin, interferon alfa-2a (IFN), fluorouracil (5-FU),
      hydroxyurea (HU) and radiotherapy. METHODS: Phase I cohort design establishing
      the maximal tolerated dose (MTD) of cisplatin with and without granulocyte colony
      stimulating factor (GCSF). For the first six dose levels, a 4-week cycle
      consisted of escalating doses of cisplatin during weeks 1 and 2, IFN (week 1),
      and 5-FU and HU (week 2) with single daily radiation fractions of 200 cGy during
      days 1-5 of weeks 1-3 and no treatment in week 4. When dose-limiting neutropenia
      was encountered. GCSF was added during weeks 1, 3, and 4. Finally, to decrease
      esophagitis, the radiotherapy schedule was altered to 150 cGy twice daily during
      weeks 1 and 2, followed by a 2-week break (level 7). RESULTS: Forty-nine patients
      with refractory chest malignancies were treated. The MTD of this regimen without
      GCSF was cisplatin 50 mg/m2 in weeks 1 and 2, IFN 5 million Units (MU)/m2 per day
      on days 1-5 in week 1, 5-FU 800 mg/m2 per day for 5 days by continuous infusion,
      and HU 500 mg every 12 h for 11 doses during week 2. The addition of GCSF during
      weeks 1, 3, and 4 allowed for escalation of cisplatin to 100 mg/m2 during weeks 1
      and 2, with a decreased dose of IFN at 2.5 MU/m2 per day to avoid renal toxicity.
      Dose-limiting toxicity (DLT) included severe neutropenia, thrombocytopenia, and
      esophagitis in 5 of 13 patients. Increased thrombocytopenia in patients receiving
      GCSF was not observed. During hyperfractionated radiotherapy (level 7)
      chemotherapy doses were as above except for a reduction of 5-FU to 600 mg/m2 per
      day. While severe esophagitis was reduced, grade 4 thrombocytopenia became more
      prevalent and was seen in 6 of 7 patients. In-field tumor responses were observed
      in 17 of 28 evaluated patients with non-small-cell lung cancer. The median times
      to progression and survival were 4 and 6 months, respectively. When only patients
      with all known disease confined to the radiotherapy field were considered the
      corresponding times were 6 and 15 months, respectively. Most treatment failures
      occurred outside of the irradiated field. CONCLUSIONS: (1) This intensive
      multimodality regimen can be given with aggressive supportive care incorporating
      GCSF. The recommended phase II doses for a 4-week cycle are cisplatin 50 mg/m2
      week 1, and 100 mg/m2 week 2, IFN 2.5 MU, HU 500 mg every 12 h x 11 and 5-FU 800
      mg/m2 per day with single fraction radiotherapy during weeks 1-3 and GCSF during
      weeks 1, 3, and 4. (2) GCSF can be safely administered and provides effective
      support of neutrophils when administered simultaneously with IFN, cisplatin, and
      chest radiotherapy. (3) There is synergistic renal toxicity when high doses of
      IFN and cisplatin are given together. (4) Hyperfractionated radiotherapy
      decreases the severity of esophagitis but increases thrombocytopenia. (5)
      Although highly toxic, response rates, time to progression and survival figures
      with this regimen are encouraging and support its investigation in the phase II
      setting.

PMID- 7530176
TI  - Decay-accelerating factor protects human trophoblast from complement-mediated
      attack.
AB  - Approximately one-fifth of first trimester losses can be characterized by the
      onset of hypocomplementemia prior to ultrasonographic loss of embryonic
      viability. Monoclonal antibodies to the membrane complement regulatory protein,
      decay-accelerating factor (DAF), were bound to the surface of trophoblastic
      tissues, with the estimated number of DAF molecules in tissues obtained from
      hypocomplementemic women less than those from normocomplementemic women
      (approximately 10%). While trophoblastic tissue obtained from normocomplementemic
      women did not decomplement normal human sera, pretreatment of this tissue with
      anti-DAF antibodies resulted in activation of the complement (C') system via the
      alternate C' pathway (ACP). If trophoblastic tissue from normocomplementemic
      women was pretreated with phospholipase C, decomplementation of human serum
      occurred. These data strongly suggest that trophoblasts evade the ACP with
      functional DAF, possibly through absorption of the molecule's lipophilic
      diacylglycerol membrane-anchored moiety into the outer lipid bilayer of the
      trophoblast and may be a rational means for the utilization of immunotherapy in
      recurrent spontaneous aborters.

PMID- 7530177
TI  - Failed metallic biliary stents: causes and management of delayed complications.
AB  - OBJECTIVE: To describe the incidence, management and long-term outcome of metal
      stent failure in patients with malignant biliary obstruction. SUBJECTS AND
      METHODS: Sixty-nine patients received a total of 93 metallic biliary stents for
      relief of malignant biliary obstruction. Twenty-nine patients had hilar tumours;
      40 had common bile duct tumours. RESULTS: Ten of 69 patients (14%) presented with
      stent occlusion at a mean interval of 4 months after stent insertion. Five of 29
      patients (17%) with hilar lesions and five of 40 patients (12%) with common bile
      duct lesions had stent occlusion. Occlusion was due to tumour overgrowth in eight
      patients and to occlusion by debris in two. The eight patients with tumour
      overgrowth were treated with internal/external catheters (5 patients), no therapy
      (2 patients), and further metal stents (1 patient). These eight patients with
      tumour overgrowth had a limited lifespan after tumour overgrowth occurred with a
      mean survival of 2.6 months. The two patients with occlusion due to debris were
      treated by sweeping the stent with a balloon catheter and these patients survived
      26 and 27 months, respectively. CONCLUSION: Adequate peripheral purchase in the
      biliary tree and overstenting are necessary to prevent tumour overgrowth when
      stenting hilar lesions. The development of stent occlusion due to tumour
      overgrowth heralds a limited survival and internal/external catheters are
      preferred over further metal stents for palliation.

PMID- 7530178
TI  - Case report: neovascularity of inferior vena cava tumour thrombus from renal cell
      carcinoma--CT and MRI appearance.
AB  - Renal cell carcinoma is a highly vascular tumour that frequently invades vascular
      structures. Neovascularization within an intravascular mass has occasionally been
      demonstrated on CT and angiography. We report a case with MR evidence of
      neovascularity in the inferior vena cava secondary to a renal cell carcinoma.

PMID- 7530179
TI  - Reticulocyte maturity pattern analysis as a predictive marker of erythropoiesis
      in paediatrics. Part I: Evaluation of age-dependent reference values.
AB  - Reticulocyte quantification in peripheral blood samples is a commonly used
      diagnostic indicator of erythropoietic activity. A methodology based on flow
      cytometry additionally separates reticulocytes into three groups by fluorescence
      staining of the residual RNA. This identifies cells as high (HFR), medium (MFR)
      and low (LFR) fluorescence intensity reticulocytes. In the present study an
      automated counter was evaluated and tested for its clinical applicability in
      paediatrics. In part I, reference intervals for different periods of childhood
      were determined. Except for the neonatal period there was no age-dependence so
      that children aged one week to 16 years have been summarized in one group. The
      wide variations we found in preterm children can be explained by different
      erythropoietic stimuli as the result of anaemia in infants with very low
      birthweight. No significant differences could be found between the sexes, not
      even at the onset of puberty. When using the reticulocyte maturity pattern
      analysis in clinical practice, the data give a helpful indication of the
      efficiency of the erythropoietic system.

PMID- 7530181
TI  - Preservative effect of aprotinin on canine plasma immunoreactive
      adrenocorticotropin concentrations.
AB  - The susceptibility of adrenocorticotropin (ACTH) in canine blood and plasma to
      enzymatic degradation has limited the availability of endogenous ACTH assay for
      veterinary use. This study examined if a proteinase (enzyme) inhibitor,
      aprotinin, mixed with blood at the time of collection, would limit the loss of
      immunoreactive (IR) ACTH from canine plasma stored at various temperatures. Blood
      was collected from laboratory-maintained dogs or dogs with hyperadrenocorticism
      and placed into EDTA-containing tubes in the presence or absence of aprotinin.
      Plasma obtained was stored for 4 d at temperatures ranging from -86 degrees C to
      room temperature (22 degrees C). Results showed that addition of aprotinin
      preserved IR-ACTH concentrations in plasma stored for 4 d at temperatures < or =
      4 degrees C, or in unfrozen plasma stored inside insulated shipping containers
      containing frozen refrigerant packs. Plasma collected with aprotinin and stored
      at 22 degrees C showed a slight (17-23%) but significant (P < 0.05) decline in IR
      ACTH. Unfrozen plasma collected without aprotinin showed significant (P < 0.05)
      loss of IR-ACTH during storage under identical conditions. These data indicate
      that aprotinin has a profound preservative effect upon canine plasma IR-ACTH and
      that it may be possible to submit unfrozen samples collected with this inhibitor
      to appropriate reference laboratories for analysis of IR-ACTH.

PMID- 7530180
TI  - Psychosis during interferon in eosinophilic leukaemia.

PMID- 7530183
TI  - [Interferon in injuries with HIV or HCV-contaminated needles].

PMID- 7530184
TI  - Multichannel visual evoked potentials in migraine.
AB  - Multichannel recordings of visual evoked potentials (VEPs) have proved to be
      useful in the evaluation of visual field defects. We studied the topographic
      distribution of transient VEPs in 15 migraine patients (8 with visual aura and 7
      without) and 15 age-matched controls during the migraine-free interval. All the
      subjects included in the study had normal visual fields. VEPs were recorded from
      9 electrodes placed on the posterior scalp. Stimuli were full-field and hemifield
      reversing square wave grating patterns of medium spatial frequency (4 c/deg). The
      groups did not show significant differences in latencies and amplitudes of the
      major components (N70, P100) recorded from the midline. However, migraine
      patients with visual hemianopic aura showed definite asymmetries in the VEP
      amplitude distribution. Significantly reduced, absent or polarity-invered VEP
      responses were recorded ipsilateral to the side of the prodromic visual symptoms.
      Direct comparison of affected and unaffected hemispheres by partial field
      stimulation confirmed these findings. According to the VEP cortical generator
      theory, these abnormalities suggest a functional anomaly consistent with the
      clinical syndrome and detectable also in the migraine-free interval. None of the
      migraine patients without aura or the controls showed VEP amplitude asymmetries.
      We conclude that multichannel VEP recordings may discriminate between different
      subtypes of migraine and contribute important physiopathological information to
      the study of this disease.

PMID- 7530182
TI  - Growth factor regulation of mouse primordial germ cell development.
AB  - This chapter focused on three key regulators of PGC survival and proliferation;
      SLF, LIF, and bFGF. The survival of all animal cells may require multiple
      polypeptide factors and PGCs seem to be no exception (Fig. 7). A number of lines
      of evidence suggest that membrane-bound forms of SLF may be required for PGC
      survival. These data suggest an exquisite mechanism for controlling both PGC
      survival and migration. Thus PGCs that stray from the normal migratory pathway
      might be eliminated through programmed cell death. SLF, together with LIF, can
      stimulate PGC proliferation in culture and it seems likely that LIF or a related
      cytokine may function in vivo to regulate PGC survival and proliferation. Animals
      doubly deficient in LIF and its relatives may soon allow the roles of these
      cytokines in PGC development to be determined. Although bFGF is a potent PGC
      mitogen in vitro, whether PGCs ever encounter bFGF in vivo remains questionable
      since in culture it alters both the proliferative and developmental potential of
      PGCs. TGF beta or MIS may be important negative regulators of PGC development,
      and mice lacking these factors should allow their role in PGC development to be
      assessed.

PMID- 7530186
TI  - Steady-state visually evoked potential topography during the Wisconsin card
      sorting test.
AB  - This paper describes, for the first time, changes in steady-state visually evoked
      potential (SSVEP) topography associated with the performance of a computerised
      version of the Wisconsin card sort test (WCS). The SSVEP was recorded from 64
      scalp sites and was elicited by a 13 Hz spatially uniform visual flicker
      presented continuously while 16 subjects performed the WCS. in the WCS, the sort
      criterion was automatically changed after subjects had sorted 10 cards correctly.
      Feedback on the 11th card always constituted a cue for a change in the sort
      criterion. It was found that in the 1-2 sec interval after the occurrence of the
      cue to change sort criterion, the prefrontal, central and right parieto-temporal
      regions showed a pronounced attenuation in SSVEP amplitude and an increase in
      phase lag. These changes, interpreted as an increase in regional cortical
      activity, are not apparent in the equivalent portions of the WCS when the sort
      criterion does not need to be changed. These results indicate that the levels of
      prefrontal and right parieto-temporal activity varied during the performance of
      the WCS, peaking at the times a change in sort criterion was required.

PMID- 7530185
TI  - Pain-related somatosensory evoked potentials following CO2 laser stimulation of
      foot in man.
AB  - Since our previous study of pain somatosensory evoked potentials (SEPs) following
      CO2 laser stimulation of the hand dorsum could not clarify whether the early
      cortical component N1 was generated from the primary somatosensory cortex (SI) or
      the secondary somatosensory cortex (SII) or both, the scalp topography of SEPs
      following CO2 laser stimulation of the foot dorsum was studied in 10 normal
      subjects and was compared with that of the hand pain SEPs and the conventional
      SEPs following electrical stimulation of the posterior tibial nerve recorded in 8
      and 6 of the 10 subjects, respectively. Three components (N1, N2 and P2) were
      recorded for both foot and hand pain SEPs. N1 of the foot pain SEPs was maximal
      at the midline electrodes (Cz or CPz) in all data where that potential was
      recognized, but the potential field distribution was variable among subjects and
      even between two sides within the same subject. N1 of the hand pain SEPs was
      maximal at the contralateral central or midtemporal electrode. The scalp
      distribution of N2 and P2, however, was not different between the foot and hand
      pain SEPs. The mean peak latency of N1 following stimulation of foot and hand was
      found to be 191 msec and 150 msec, respectively, but there was no significant
      difference in the interpeak latency of N1-N2 between foot and hand stimulation.
      It is therefore concluded that N1 of the foot pain SEPs is generated mainly from
      the foot area of SI. The variable scalp distribution of the N1 component of the
      foot pain SEPs is likely due to an anatomical variability among subjects and even
      between sides.

PMID- 7530187
TI  - Late ERP components in visual and auditory Go/Nogo tasks.
AB  - In an audio-visual Go/Nogo paradigm we studied whether the Go/Nogo difference,
      usually found in the time range of the visual N2, is also present after auditory
      stimuli, which bears on the common response inhibition hypothesis of this N2
      effect. Moreover the possible presence and variation of P300 subcomponents were
      studied with the goal of clarifying the reasons for the commonly observed P300
      topography changes between Go and Nogo trials. To disentangle possible P300
      subcomponents we applied a crossmodal divided attention (DA) condition, in which
      the subcomponents are known to be separated after auditory stimuli in choice
      tasks. An N2 effect was found after visual but not after auditory stimuli, which
      is evidence against the response-inhibition hypothesis. After visual stimuli a
      positive complex (P400) was seen, whereas after auditory stimuli two dissociated
      components (P400 and P507) were found instead. The P507 had a parietal maximum
      for both Go and Nogo trials. It was larger and it peaked later in Go than in Nogo
      trials. The P400 showed topographic differences between Go and Nogo trials, which
      could be explained by the overlap of the two subcomponents. We assume that (i)
      both subcomponents have a stable topography across response type, and (ii) the
      first subcomponent is invariant with response type, whereas the second (which
      overlaps the first one) is larger and peaks later on Go than on Nogo trials.

PMID- 7530189
TI  - A comparative study of ERP correlates of psychometric and Piagetian intelligence
      measures in normal and hyperactive children.
AB  - Verbal and performance scores of the Wechsler Intelligence Scale for Children
      Revised (WISC-R 1981) and of a Piagetian battery, the Cognitive Development Scale
      for Children (EDC 1984), were obtained on 30 normal control and 19 hyperactive 6
      8-year-old children. Amplitudes and latencies of a fronto-central P250 and of the
      parieto-occipital N250, P350 and P500 were measured concurrently in 4
      categorization tasks derived from tests of the WISC-R and EDC batteries. Spearman
      correlations were computed between the intelligence and the ERP factor scores.
      Results showed that age-related and age-corrected Wechsler's scores were
      correlated with similar ERP changes (reduced amplitude, decreased latency). With
      regard to the amplitude changes, each type of intelligence was associated with a
      specific ERP pattern. The verbal scores were correlated with the P350 and the
      P500 amplitudes, and the performance scores with the frontal P250 and occipital
      N250 amplitudes. By contrast, Piagetian development and intelligence scores
      yielded ERP correlates in the opposite direction: P500 amplitude was negatively
      correlated with raw EDC scores, but positively with scaled EDC scores. In
      addition, Piagetian intelligence was not related to the general peak latency
      decrease with age. In hyperactive children, additional negative correlations were
      found between P250 amplitude and the subjects' verbal test scores. Correlations
      with some performance tests that were negative in normal controls, were positive
      in hyperactive children. In addition, latency-based correlations found in normal
      controls were lacking in hyperactive children. These findings provide strong
      evidence that intelligence comprises different components related to different
      subsets of cognitive processes, as indexed by different ERP waves. They also
      suggest that the development and intelligence do not always rely on the same
      changes, and that intelligence forms may not be referred to the same use of the
      same processes in hyperactive and normal children.

PMID- 7530188
TI  - Is "memory-scanning" time in the Sternberg paradigm reflected in the latency of
      event-related potentials?
AB  - The time taken to scan short term memory for a target (probe) digit in the
      Sternberg paradigm is thought to be reflected in the latency of a major positive
      wave in the associated event-related potentials. In the present study we have
      recorded and analysed reaction time and event-related potentials to a digit probe
      identification task in 37 healthy subjects. Using methods similar to those of
      earlier studies, we have confirmed the previously reported relationship between
      memory set size and the apparent latency of the major positive wave. However,
      analysis of the responses of individual subjects showed that increasing set size
      had no consistent effects on this wave. One-third of the subjects showed no
      latency change with increasing set size. In the other subjects, possible latency
      changes were invariably associated with wave form changes, suggesting that
      impression of latency shifts may arise from a comparison of non-analogous waves.
      We suggest that the most significant effect of increasing set size, in the
      majority of subjects, is a negative amplitude shift which overlaps and distorts a
      variable section of the major positive wave. In these subjects, an apparent shift
      in the latency of the major positive wave could be attributed to a combination of
      attenuation of earlier contributions and relative preservation of later subpeaks,
      with the result that the dominant positive waves at different levels of memory
      load are not analogous. By contrast, reaction time increased with set size in all
      subjects, irrespective of the presence or absence of associated wave form
      changes. Whereas the reaction time changes with increasing memory load in our
      study support the original concept of memory scanning, we found no consistent
      relationship between the latency of event-related potentials generated by this
      digit probe identification task and memory load. While the presence or absence of
      a latency shift in some subjects may be open to interpretation, our findings do
      not support the hypothesis that the latency of the major positive waves is an
      index of the time involved in memory scanning.

PMID- 7530190
TI  - Somatosensory evoked potential spinal cord monitoring reduces neurologic deficits
      after scoliosis surgery: results of a large multicenter survey.
AB  - Neurologic deficits were compared to somatosensory evoked potential (SEP) spinal
      cord monitoring in a survey of spinal orthopedic surgeons. Experienced SEP spinal
      cord monitoring teams had fewer than one-half as many neurologic deficits per 100
      cases compared to teams with relatively little monitoring experience. Experienced
      SEP monitoring teams also had fewer neurologic deficits than were seen in
      previous surveys of this group. Definite neurologic deficits, despite stable SEPs
      (false negative monitoring), occurred during surgery in only 0.063% of patients.
      Factors independently associated with fewer neurologic deficits also included the
      surgeon's years of experience in orthopedic surgery and the use of the wake-up
      test. Other technical survey results are also presented here. These results
      confirm the clinical efficacy of experienced SEP spinal cord monitoring for
      prevention of neurologic deficits during spinal surgery such as for scoliosis.

PMID- 7530191
TI  - Readiness to respond in a target detection task: pre- and post-stimulus event
      related potentials in normal subjects.
AB  - Brain potentials were recorded from 12 normal subjects engaged in an auditory
      target detection task (target stimulus probability of 0.2, stimulus rate of 1
      every 2 sec) when instructions were (1) to press a response button with the thumb
      of the dominant hand to each target or (2) to keep a mental count of each target.
      A pre-stimulus slow negative potential was identified before every stimulus
      except non-targets immediately after targets. The amplitude of the pre-stimulus
      negativity was significantly affected by task instructions and was up to 4 times
      larger during the button press than the mental count condition. In contrast, the
      amplitudes and latencies of the event-related components (N100, P200, N200 and
      P300), when slow potentials were removed by filtering, were not different as a
      function of press or count instructions. The immediately preceding stimulus
      sequence affected both the amplitude and onset latency of the pre-stimulus
      negativity; both measures increased as the number of preceding non-targets
      increased. The amplitude of the pre-stimulus negative shift to targets also
      increased significantly as RT speed decreased. The major portion of the pre
      stimulus negative potential is considered a readiness potential (RP) reflecting
      preparations to make a motor response. The amplitude of the RP during the target
      detection task did not significantly lateralize in contrast to the RP
      accompanying self-paced movements.

PMID- 7530192
TI  - Pitch change of a continuous tone activates two distinct processes in human
      auditory cortex: a study with whole-head magnetometer.
AB  - Previous studies have shown that a frequency change in a continuous tone elicits
      an NI type of ERP (event-related potential) component. It remained unclear,
      however, whether this response is a "genuine" N1 (onset detector response) or the
      mismatch negativity (MMN), a change-detector type of ERP response, elicited in
      previous studies by an infrequent change in a sequence of homogeneous stimuli. A
      further possibility is a nearly perfect overlap of the two types of ERP
      components. The advent of modern, high-resolution magnetometers has opened a new,
      powerful way to tackle such component-overlap problems. Subjects were presented
      with a continuous tone of 988 Hz which was occasionally increased to 1108 Hz for
      a period of 100 msec. The magnetic responses to this change consisted of two
      partially overlapping components with peaks separated by 30 msec. The earlier
      component was probably generated by neuronal populations of the auditory cortex
      corresponding to the supratemporal N1, whereas the later one, generated
      anteriorly and inferiorly to the first, probably reflects a mismatch process
      causing the magnetic equivalent of the electrical MMN.

PMID- 7530193
TI  - Actions of vitamin D3, analogs on human prostate cancer cell lines: comparison
      with 1,25-dihydroxyvitamin D3.
AB  - Data from epidemiological studies has suggested that vitamin D deficiency may
      promote prostate cancer, although the mechanism is not understood. We have
      previously demonstrated the presence of vitamin D receptors (VDR) in three human
      prostate carcinoma cell lines (LNCaP, PC-3, and DU-145) as well as in primary
      cultures of stromal and epithelial cells derived from normal and malignant
      prostate tissues. We have also shown that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]
      can elicit an antiproliferative action in these cells. In the present study we
      compared the biological actions of 1,25-(OH)2D3 to those of a series of natural
      vitamin D3 metabolites and several synthetic analogs of vitamin D3 known to
      exhibit less hypercalcemic activity in vivo. In ligand binding competition
      experiments, we demonstrated the following order of potency in displacing
      [3H]1,25-(OH)2D3 from VDR: EB-1089 > 1,25-(OH)2D3 > MC-903 > 1,24,25-(OH)3D3 > 22
      oxacalcitriol (OCT) > 1 alpha,25-dihydroxy-16-enecholecalciferol (Ro24-2637) > 25
      hydroxyvitamin D3, with EB-1089 being approximately 2-fold more potent than the
      native hormone. No competitive activity was found for 25-hydroxy-16,23-diene
      cholecalciferol. When compared for ability to inhibit proliferation of LNCaP
      cells, MC-903, EB-1089, OCT, and Ro24-2637 exhibited 4-, 3-, and 2-fold greater
      inhibitory activity than 1,25-(OH)2D3. Interestingly, although OCT and Ro24-2637
      exhibit, respectively, 10 and 14 times lower affinity for VDR than 1,25-(OH)2D3,
      both compounds inhibited the proliferation of LNCaP cells with a potency greater
      than that of the native hormone. The relative potency of vitamin D3 metabolites
      and analogs to inhibit cell proliferation correlated well with the ability of
      these compounds to stimulate prostate-specific antigen secretion by LNCaP cells
      as well as with their potency to induce the 25-hydroxyvitamin D3-24-hydroxylase
      messenger RNA transcript in PC-3 cells. In conclusion, these results demonstrate
      that synthetic analogs of vitamin D3, known to exhibit reduced calcemic activity,
      can elicit antiproliferative effects and other biological actions in LNCaP and PC
      3 cell lines. It is noteworthy that although binding to VDR is critical for 1,25
      (OH)2D3 action, the analog data indicate that additional factors significantly
      contribute to the magnitude of the biological response. Finally, the strong
      antiproliferative effects of several synthetic analogs known to exhibit less
      calcemic activity than 1,25-(OH)2D3 suggest that these compounds potentially may
      be useful as an additional therapeutic option for the treatment of prostate
      cancer.

PMID- 7530194
TI  - Domains of rat interleukin 1 beta involved in type I receptor binding.
AB  - In the present study the inhibitory effects of a panel of 21 monoclonal
      antibodies (moabs) to rat interleukin 1 beta (rIL-1 beta) on the binding of 125I
      labeled rIL-1 beta to murine type I IL-1 receptors on EL4 cells were
      investigated. Furthermore, the epitopes of these moabs were determined by the use
      of the pepscan technique, and these epitopes were visualized on a three
      dimensional model of rIL-1 beta. Some moabs (SILK 3, 4, 5, 6, and 22) inhibited
      receptor binding of radioiodinated rIL-1 beta at concentrations that are similar
      to the dissociation constant values of antibody-rIL-1 beta binding. Another group
      of moabs (SILK 7, 11, 20, 21, and 23) also inhibited receptor binding but only at
      concentrations that are 10-150 times higher than their dissociation constants. A
      large group of moabs did not affect receptor binding in the concentration range
      tested, and two moabs enhanced the binding of rIL-1 beta to type I receptors. The
      result of pepscan analysis shows that the moabs bound to one or more of the amino
      acid sequences 35-49, 66-85, 78-97, 106-124, and 123-143 of mature rIL-1 beta.
      Modeling of rIL-1 beta shows that the binding domains of SILK 4, 5, 6, and 22
      (sequence 123-143) is located at the closed end of the molecule, indicating that
      this part of rIL-1 beta harbors domains that are crucial for type I receptor
      binding. The binding domain of SILK 3 (sequence 66-85) is also located at this
      end of the molecule. In contrast, the binding domains of SILK 7, 11, 20, 21, and
      23 (sequence 78-97) are located at the open end of the molecule, which is at the
      same face as the amino- and carboxy-terminals. The binding domain of SILK 16
      (sequence 106-124) is positioned at the center of the molecule. It is concluded
      that the closed end of rIL-1 beta contains sequences that are crucial for its
      binding to type I receptors on murine EL4 cells. Because of the high
      concentrations of antibodies to residues 78-97 of rIL-1 beta that are needed to
      interfere with receptor binding, the importance of these domains in binding to
      type I receptors remains uncertain.

PMID- 7530195
TI  - Asparagine-linked oligosaccharides facilitate human chorionic gonadotropin beta
      subunit folding but not assembly of prefolded beta with alpha.
AB  - To determine the role of asparagine (N)-linked oligosaccharide chains in protein
      folding and assembly, the well established hCG-beta in vitro folding and assembly
      assays were used to analyze how the human CG (hCG) beta-subunit devoid of one or
      two N-linked glycans folds and assembles under different conditions. Two
      approaches were used: 1) site-specific mutagenesis of hCG-beta synthesized in
      Chinese hamster ovary cells transfected with beta-mutants lacking the asparagine
      glycosylation sites; and 2) enzymatic deglycosylation of hCG-beta synthesized in
      JAR cells with peptide N-glycosidase F or endoglycosidase H. In both cases,
      [35S]cysteine-labeled beta-subunits were used as substrates to measure the
      conversion of the hCG-beta folding intermediate p beta 1 into p beta 2 and
      assembly of p beta 2 with urinary alpha. Using the mutated substrates from
      Chinese hamster ovary cells, it was found that 60% of wild-type p beta 1 (two N
      linked glycans), 60% of p beta 1 missing the Asn13-linked glycan, 40% of p beta 1
      missing the Asn30-linked glycan, and 10% of p beta 1 missing two N-linked glycans
      were converted to the corresponding p beta 2, respectively. With the
      enzymatically deglycosylated substrate from JAR cells, 90% of p beta 1 (two N
      linked glycans), 70% of p beta 1(1) (one N-linked glycan), and 10% of p beta 1(0)
      (without N-linked glycan) folded into p beta 2 under cysteamine and cystamine
      redox conditions with or without protein disulfide isomerase. These data
      demonstrate that at least one N-linked glycan is required for efficient folding
      of hCG-beta and that the Asn30-linked glycan is more important than Asn13-linked
      glycan for hCG-beta folding. It also was shown that the composition of N-linked
      glycans of hCG-p beta 1 did not change protein folding, since hCG-beta substrates
      with high mannose oligosacharides folded as efficiently as beta-substrates
      containing sialylated complex oligosaccharides. Moreover, assembly of the already
      folded, assembly-component folding intermediate, p beta 2, was not affected by
      removal of one or both of the N-linked glycans of the beta-subunit. These data
      thus show that N-linked glycans play their most important role in the folding
      component of the folding and assembly pathway for hCG-beta.

PMID- 7530196
TI  - Insulin-like growth factor-I (IGF-I) and IGF-binding proteins in bovine sera and
      pituitaries at different stages of the estrous cycle.
AB  - The objective of this study was to determine whether concentrations of
      hypophyseal and serum insulin-like growth factor-I (IGF-I) and binding activities
      of serum and hypophyseal IGF-binding proteins (IGFBPs) differ with stage of the
      estrous cycle in mature beef cows. Cows were assigned to the following stages of
      the estrous cycle based on serum concentrations of progesterone (P4) and ovarian
      structures at death: days 1-5 (day 0 = estrus; n = 18), days 6-10 (n = 24), days
      11-16 (n = 39), and days 17-21 (n = 7). Serum samples collected at death and
      anterior pituitary homogenates were analyzed for IGF-I, LH, and FSH by RIA. Serum
      and pituitary IGFBPs were evaluated by ligand and immunoblot analyses. Serum
      samples contained IGFBP activity at 44 and 40 kilodaltons (kDa; IGFBP-3), 34 kDa
      (IGFBP-2), 30 kDa (IGFBP-5), 28 kDa, and 24 kDa. The intensity of binding by the
      different sized proteins in serum remained constant throughout the estrous cycle.
      IGFBPs detected in anterior pituitaries included a 36-/40-kDa doublet (IGFBP-3),
      a 32-kDa protein (IGFBP-2), and a 29-kDa IGFBP (IGFBP-5). The intensity of
      [125I]IGF-I binding to IGFBPs was greater (P < 0.05) during days 11-16 than days
      1-5 or days 6-10 of the estrous cycle and was intermediate (P > 0.05) during days
      17-21. Serum concentrations of LH were low (< 0.4 ng/ml) during days 1-16 of the
      estrous cycle, but increased (P < 0.05) approximately 3- to 4-fold during days 17
      21. LH concentrations in the anterior pituitary increased (P < 0.05) from the
      postovulatory period (548 +/- 52 micrograms/g; days 1-5) to the late luteal phase
      (791 +/- 39 micrograms/g; days 11-16) and were intermediate (P > 0.05) during the
      preovulatory phase (707 +/- 85 micrograms/g; days 17-21). Concentrations of IGF-I
      and FSH in the anterior pituitary and serum did not differ (P > 0.05) by stage of
      the estrous cycle. A positive correlation among the different IGFBPs in the
      pituitary (P < 0.01) and between each pituitary IGFBP and serum P4 (P < 0.05)
      existed. The significance (P < 0.0002) of the correlation between pituitary IGFBP
      3 and P4 was greater (P < 0.02) than that between the other pituitary IGFBPs and
      P4. In summary, IGFBP activity in the anterior pituitary, but not that in serum,
      changed with stage of the estrous cycle in association with serum concentrations
      of P4. The absence of similar changes in serum or anterior pituitary
      concentrations of IGF-I supports the hypothesis that IGFBPs may regulate the
      actions of IGF-I on gonadotropin release from the anterior pituitary gland during
      the estrous cycle of beef cattle.

PMID- 7530197
TI  - Constitutive activation of the Fas ligand gene in mouse lymphoproliferative
      disorders.
AB  - Mice homozygous for lpr (lymphoproliferation) or gld (generalized
      lymphoproliferative disease) develop lymphadenopathy and splenomegaly and suffer
      from autoimmune disease. The lpr mice have a defect in a cell-surface receptor,
      Fas, that mediates apoptosis, while gld mice have a mutation in the Fas ligand
      (FasL). Northern hybridization with the FasL cDNA as probe indicated that the
      cells accumulating in lpr and gld mice abundantly express the FasL mRNA without
      stimulation. By means of in situ hybridization and immunohistochemistry, we
      identified the cells expressing the FasL mRNA as CD4-CD8- double negative T
      cells. The T cells from lpr mice were specifically cytotoxic against Fas
      expressing cells. Since FasL is normally expressed in activated mature T cells
      these results indicate that the double negative T cells accumulating in lpr and
      gld mice are activated once, and support the notion that the Fas/FasL system is
      involved in activation-induced suicide of T cells. Furthermore, the graft-versus
      host disease caused by transfer of lpr bone marrow to wild-type mice can be
      explained by the constitutive expression of the FasL in lpr-derived T cells.

PMID- 7530200
TI  - Influence of a Ca2+ channel agonist, Bay k-8644, on the anticonvulsant activity
      of NMDA and non-NMDA receptor antagonists.
AB  - Bay k-8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro- methylphenyl)
      pyridine-5-carboxylate) (a Ca2+ channel agonist of the dihydropyridine class) at
      5 mg/kg (s.c.) impaired the anticonvulsant activities of two competitive NMDA
      receptor antagonists, CGP 37849 (D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic
      acid) and D-CPP-ene (3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid)
      (given i.p.), against electroconvulsions. In contrast, the Ca2+ channel agonist
      did not affect the protection afforded by the AMPA receptor antagonists, NBQX
      (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline) and GYKI 52466 (1-(4
      aminophenyl)-4-methyl-7,8-methylendioxy-5-2,3-benzodiazepine ), or by a non
      competitive NMDA receptor antagonist, MK-801 (dizocilpine), all being injected
      i.p. It may be concluded that the anticonvulsive activity of competitive NMDA
      receptor antagonists can be impaired by Ca2+ ion influx.

PMID- 7530199
TI  - Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients
      with metastatic prostate cancer.
AB  - Rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP) has been used for the
      palliative treatment of metastatic bone pain. A phase 1 dose escalation study was
      performed using 186Re-HEDP. Twenty-four patients with hormone-resistant prostate
      cancer entered the study. Each patient had at least four bone metastases and
      adequate haematological function. Groups of at least three consecutive patients
      were treated with doses starting at 1295 MBq and increasing to 3515 MBq
      (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose
      limiting toxicity, while leucopenia played a minor role. Early death occurred in
      one patient (10 days after administration) without clear relationship to the
      186Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two
      patients who received 3515 MBq 186Re-HEDP showed grade 3 toxicity (thrombocytes
      25-50 x 10(9)/l), defined as unacceptable toxicity. After treatment alkaline
      phosphatase levels showed a transient decrease in all patients (mean: 26% +/- 10%
      IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight
      patients, preceded by a temporary increase in three patients. From this study we
      conclude that the maximally tolerated dose of 186Re-HEDP is 2960 MBq. A placebo
      controlled comparative study on the efficacy of 186Re-HEDP has been initiated.

PMID- 7530202
TI  - Nitric oxide involvement in sodium choleate-induced fluid secretion and diarrhoea
      in rats.
AB  - Bile salt-induced diarrhoea, net water and electrolyte secretion,
      gastrointestinal transit and nitric oxide (NO) synthase activity were studied in
      rats. NG-Nitro-L-arginine methyl ester (2.5-25 mg/kg i.p.), an inhibitor of NO
      synthase, and dexamethasone (0.03-0.3 mg/kg i.p.), an inhibitor of the inducible
      isoform of NO synthase, antagonized the diarrhoeal response. The NO precursor, L
      arginine and isosorbide-5-mononitrate (an NO donor), reversed the inhibitory
      effect of NG-nitro-L-arginine methyl ester. The bile salt-stimulated fluid
      secretion, transit through the gut and NO synthase all were inhibited by NG-nitro
      L-arginine methyl ester (but not NG-nitro-D-arginine methyl ester). NO synthase
      activity also was inhibited by dexamethasone. The results are consistent with
      bile salt induction of epithelial cell injury and concomitant synthesis of NO,
      mainly through activation of the inducible form of the enzyme. We believe that in
      this study NO is a mediator of intestinal secretion and motility changes that
      enhance transit of luminal contents through the gut, resulting in diarrhoea.

PMID- 7530198
TI  - How MHC class II molecules reach the endocytic pathway.
AB  - We have examined trafficking of major histocompatibility complex (MHC) class II
      molecules in human B cells exposed to concanamycin B, a highly specific inhibitor
      of the vacuolar H(+)-ATPases required for acidification of the vacuolar system
      and for early to late endosomal transport. Neutralization of vacuolar
      compartments prevents breakdown of the invariant chain (Ii) and blocks conversion
      of MHC class II molecules to peptide-loaded, SDS-stable alpha beta dimers. Ii
      remains associated with alpha beta and this complex accumulates internally, as
      ascertained biochemically and by morphological methods. In concanamycin B-treated
      cells, a slow increase (> 20-fold) in surface expression of Ii, mostly complexed
      with alpha beta, is detected. This surface-disposed fraction of alpha beta Ii is
      nevertheless a minor population that reaches the cell surface directly, or is
      routed via early endosomes as intermediary stations. In inhibitor-treated cells,
      the bulk of newly synthesized alpha beta Ii is no longer accessible to fluid
      phase endocytic markers. It is concluded that the majority of alpha beta Ii is
      targeted directly from the trans-Golgi network to the compartment for peptide
      loading, bypassing the cell surface and early endosomes en route to the endocytic
      pathway.

PMID- 7530201
TI  - Ca(2+)-dependent and Ca(2+)-independent exhaled nitric oxide, presence in germ
      free animals, and inhibition by arginine analogues.
AB  - Nitric oxide (NO) was detected by chemiluminescence in exhaled air from awake
      humans, anaesthetized rabbits, guinea pigs, germ-free rats and conventional rats.
      Rabbits exhibited the highest concentrations, followed by guinea pigs, humans and
      rats. There was no significant difference between germ-free rats and control
      rats. The authenticity of NO was confirmed in cold-trap experiments. Intravenous
      administration of inhibitors of NO synthase (0.01-300 mg kg-1) to guinea pigs
      dose dependently reduced NO concentrations in exhaled air with the following
      potency order: L-N omega-nitro-arginine-methylester > asymmetric NG,NG-dimethyl-L
      arginine-dihydrochloride = L-NG-mono-methyl -arginine = L-N5- (1-iminoethyl)
      ornithine = aminoguanidine > L-canavanine. The effect of the NO synthase
      inhibitors was partly or fully reversed by L-arginine (1 g kg-1 i.v.), and L
      arginine per se induced a significant increment of NO in exhaled air. In rats, L
      N omega-nitro-arginine-methylester was considerably less potent than in guinea
      pigs. The concentration of NO in exhaled air increased 3-fold when changing from
      in situ blood auto-perfusion of rabbit lungs to in situ perfusion with saline
      medium. Addition of L-N omega-nitro-arginine-methylester to the saline perfusion
      medium evoked a reduction of NO concentrations in the air from the ventilated
      perfused lungs. Perfusion of lungs with Ca(2+)-free medium induced significant
      decrements in NO concentrations in exhaled air, an effect partly reversed upon
      reintroducing Ca2+ into the medium. In conclusion, NO was detected in exhaled air
      from humans and animals by chemiluminescence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530204
TI  - Blockade of the discriminative stimulus effects of DOI by MDL 100,907 and the
      'atypical' antipsychotics, clozapine and risperidone.
AB  - In a drug discrimination paradigm, the 5-HT2A/2C receptor antagonists,
      ritanserin, ICI 169,369 (2-(2-dimethylaminoethylthio-3-phenylquinoline
      hydrochloride) and mianserin, and the preferential 5-HT2A receptor antagonist,
      ketanserin, antagonised the discriminative stimulus effects of the 5-HT2A/2C
      receptor agonist, DOI ((2,5-dimethoxy-4-iodohenyl)-2-aminopropan) (0.63 mg/kg
      i.p.). Effective dose50 (ED50) values were: 0.32, 0.39, 0.15 and 0.03 mg/kg s.c.,
      respectively. While the novel, selective 5-HT2C receptor antagonist, SB 200,646
      (N-(1-methyl-5-iodolyl)-N'-(3-pyridyl) urea hydrochloride) was inactive (10 mg/kg
      s.c. and 20 mg/kg p.o.), the highly selective 5-HT2A receptor antagonist, MDL
      100,907 (R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl]-4-
      piperidine-methanol) very potently (ED50 = 0.0006) abolished the action of DOI.
      MDL 100,907 may display antipsychotic properties and the 'atypical'
      antipsychotics, clozapine, risperidone and sertindole, each of which possesses
      marked affinity at 5-HT2A receptors, abolished the discriminative stimulus
      effects of DOI (ED50 values of 0.07, 0.03 and 0.33 mg/kg, respectively). In
      contrast, haloperidol (0.16) was ineffective. These data demonstrate that 5-HT2A
      receptors mediate the discriminative stimulus effects of DOI and support the
      hypothesis that an antagonistic action at 5-HT2A receptors contributes to the in
      vivo actions of 'atypical' antipsychotics.

PMID- 7530206
TI  - Galanin receptors in human hypothalamus: biochemical and structural analysis.
AB  - Galanin receptors have been characterized in normal human hypothalamus using 125I
      galanin binding assays. Competition experiments of porcine 125I-galanin binding
      to human hypothalamic membranes with native human, porcine and rat galanin (10(
      11) M to 10(-8) M) gave comparable results with IC50 close to 0.1 nM. Scatchard
      analysis indicated one type of high affinity binding sites (Kd = 0.11 nM) with a
      capacity of 460 fmol/mg protein. Galanin-(1-15) and galanin-(2-29) inhibited
      tracer binding (IC50 = 1.5 nM), galanin-(3-29) and galanin-(10-29) being
      inactive. The galanin receptor antagonist, galantide, 10(-14) M to 10(-8) M, also
      strongly displaced binding of 125I-galanin to the human receptor (IC50 close to
      0.15 nM). Guanine nucleotides (from 10(-8) M to 10(-4) M) decreased tracer
      binding to human membranes by increasing the dissociation of the galanin-receptor
      complexes. Structural analysis by covalent labelling indicated that the human
      galanin receptor behaves as a monomeric protein with a molecular mass of 54,000
      daltons.

PMID- 7530203
TI  - Oxotremorine-M activates single nicotinic acetylcholine receptor channels in
      cultured Xenopus myocytes.
AB  - Oxotremorine methiodide (oxotremorine-M) is the quaternary amine derivative of
      oxotremorine and is known to be a potent and oft-reported pure, muscarinic
      receptor agonist. We report here, for the first time, that oxotremorine-M also
      has strong nicotinic actions at the single channel level. Although previous
      reports have suggested that oxotremorine-M has mixed cholinergic properties, its
      nicotinic actions have only been reported in systems which contain both
      muscarinic and nicotinic receptors, or in skeletal neuromuscular systems where
      the site of action of oxotremorine-M may have been ambiguous. We tested the
      possibility that oxotremorine-M is a nicotinic receptor agonist by examining the
      responses of single nicotinic acetylcholine receptors in primary cultures of
      myocytes from skeletal myotomes of Xenopus larvae. Myotomal myocytes are known to
      express the nicotinic acetylcholine receptor and no evidence exists that
      muscarinic receptors are expressed in these progenitors of the skeletal
      musculature. Furthermore, because we used aneural myocyte cultures, the effects
      of oxotremorine-M cannot be attributed to action on presynaptic receptors. Using
      cell-attached patches, we compared the responses of the nicotinic acetylcholine
      receptors to suberyldicholine and oxotremorine-M. Our results show that (1) both
      agonists activate the receptor channel in nanomolar concentrations; (2) the mean
      channel open-time is significantly smaller in oxotremorine-M; and (3) activation
      of the nicotinic acetylcholine receptor by oxotremorine-M is accompanied by a
      large percentage of short openings and a high frequency of event flickering. We
      conclude that oxotremorine-M is a mixed function agonist, showing partial
      blocking behavior, which effectively activates pure nicotinic acetylcholine
      receptors.

PMID- 7530207
TI  - Characterisation of [125I][MePhe7]neurokinin B binding to tachykinin NK3
      receptors: evidence for interspecies variance.
AB  - Human tachykinin NK3 receptors expressed in Chinese hamster ovary (CHO-K1) cells
      were characterised using the novel radioligand
      [125I]iodohistidyl,[MePhe7]neurokinin B ([125I][MePhe7]neurokinin B).
      [125I][MePhe7]neurokinin B was shown to label human NK3 binding sites with high
      affinity in a saturable and reversible manner. The rank order of affinity of a
      range of tachykinin ligands confirmed that the tachykinin receptor expressed was
      the NK3 receptor type. An interspecies comparison of NK3 binding sites revealed
      pharmacological differences between human, guinea pig and rat tachykinin NK3
      receptors. The NK2 selective antagonist SR 48968, inhibited binding of
      [125I][MePhe7]neurokinin B to NK3 binding sites with Ki values of 287 nM and 205
      nM in human and guinea pig respectively, but was > 30-fold less active in the
      rat.

PMID- 7530205
TI  - Modulatory mechanisms of cyclic AMP-stimulated steroid content in rat brain
      cortex.
AB  - The modulation of cyclic AMP dependent neurosteroidogenesis was studied in minces
      prepared from the cerebral cortex of adult rat. Forskolin or dibutyryl-cyclic AMP
      enhanced pregnenolone and progesterone production in a time and dose-dependent
      manner. The forskolin effect was mimicked by the cyclic AMP phosphodiesterase
      inhibitor isobutyl-methyl-xanthine, but not by the adenylate cyclase inactive
      forskolin analogue 1,9,dideoxy-forskolin. 4'-Chloro-diazepam, a high affinity
      ligand for the mitochondrial diazepam binding inhibitor (DBI) receptor, also
      elicited a time dependent increase in steroidogenesis. The forskolin and the 4'
      chloro-diazepam stimulated pregnenolone increase was prevented by preexposing the
      rat brain cortical minces to 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3
      isoquinoline carboxamide (PK 11195), a high affinity ligand for the mitochondrial
      DBI receptor endowed with antagonistic properties. The protein synthesis
      inhibitor cycloheximide prevented the forskolin and 4'-chloro-diazepam
      stimulation of pregnenolone formation. In brain cortical minces of
      adrenalectomised/orchiectomised rats dibutyryl-cyclic AMP increased both
      pregnenolone and progesterone formation, while forskolin only increased
      progesterone. These data show that cyclic AMP enhances brain steroidogenesis by
      acting on a labile protein substrate which interacts with the mitochondrial DBI
      receptor.

PMID- 7530208
TI  - Characterization of tachykinin mediated increases in [Ca2+]i in Chinese hamster
      ovary cells expressing human tachykinin NK3 receptors.
AB  - The nature of the senktide response of the human NK3 receptor expressed in
      Chinese hamster ovary cells was characterised using the Ca2+ sensitive dye Fura-2
      and imaging methods. Application of the NK3 receptor agonist senktide caused an
      increase in [Ca2+]i in the cells. The profile for NK3 receptor agonists was that
      senktide was more potent than [beta-Ala8]neurokinin A-(4-10) which was more
      potent than [Sar9,Met(O2)11]substance P. SR 48968 was a poor antagonist of the
      senktide response in intact cells confirming the weak affinity of this agent for
      the NK3 receptor (IC50 of approximately 1 microM) shown in binding assays. The
      NK3 receptor mediated increase in intracellular Ca2+ was independent of [Ca2+]o,
      blocked by the microsomal Ca2+ ATPase inhibitor thapsigargin and the
      phospholipase C inhibitor U73122 but not by ryanodine. Thus the source of the
      Ca2+ was probably a ryanodine insensitive, inositol triphosphate sensitive
      intracellular store.

PMID- 7530210
TI  - The terminal innervation patterns in young and old guinea pig heart valves: a
      quantitative analysis using acetylcholinesterase staining.
AB  - The objective of this study was to determine whether and to what extent age
      related changes occur in atrioventricular (AV) heart valve innervation. The AV
      valves from three young adult (3 months) and three older (> 24 months) female
      guinea pigs were studied. An acetylcholinesterase (AChE) localization method was
      used to prepare valve whole mounts for analysis. Two methods were used to assess
      nerve fiber density. Segments of the valves were drawn using a camera
      lucida/Nikon optiophot system. The density of nerve fibers was calculated from
      digitized images. The density of nerve fibers was also calculated by counting the
      points at which the nerve plexus intersected with the grid lines of an ocular
      graticule. In the bicuspid and tricuspid valves of the older guinea pigs, we
      observed a marked diminution in the densities of the nerve plexus, particularly
      in the basal zone, towards the free edges of the valve cusps, and in the chordae
      tendineae. Whole mount preparations such as those used in our morphological
      studies of the AV innervation may assist in elucidating the changes in other
      autonomic nerve plexuses with aging. Further work is required to establish
      whether and to what extent the loss of valve innervation influences the
      effectiveness of closure of the valves.

PMID- 7530211
TI  - All-trans-retinoic acid induces simultaneously granulocytic differentiation and
      expression of inflammatory cytokines in HL-60 cells.
AB  - All trans-retinoic acid (ATRA) can induce granulocytic differentiation both in
      vitro and in vivo, and its activity is mediated by the retinoic acid receptor
      alpha (RAR-alpha). In the present study, we evaluated the ability of this inducer
      in HL-60 cells, to stimulate simultaneously granulocytic differentiation and the
      expression of the cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-3, IL
      6, tumor necrosis factor-alpha (TNF-alpha), and stem cell factor (SCF). The level
      of expression of these cytokines in ATRA-treated HL-60 cells was compared with
      that observed in normal and lipopolysaccharide (LPS)-treated peripheral
      granulocytes. The results indicate that the expression of these cytokines is
      enhanced during differentiation so that the pattern observed in ATRA-treated HL
      60 cells is close to that of LPS-stimulated normal granulocytes. In addition,
      tetra phorbol acetate (TPA)-treated HL-60 cells express several of the above
      listed cytokines. It is concluded that ATRA not only induces granulocytic
      differentiation of HL-60 cells, but also activation of these terminally
      differentiated cells. The activating cytokine expression in these cells appears
      related to the progress of the differentiation program induced by ATRA since
      normal granulocytes do not respond to this inducer by activation of the
      expression of these genes. Furthermore, the cytokine activation is a specific
      effect of ATRA, since DMSO does not have any stimulatory effect.

PMID- 7530209
TI  - Is cyclic AMP involved in excitatory amino acid-evoked adenosine release from rat
      cortical slices?
AB  - Activation of both N-methyl-D-aspartate (NMDA) and non-NMDA receptors releases
      endogenous adenosine from superfused rat cortical slices. NMDA-evoked adenosine
      release is Ca(2+)-dependent and results from the extracellular degradation of a
      released nucleotide, whereas non-NMDA receptor activation releases adenosine per
      se in a Ca(2+)-independent manner. IBMX selectively inhibits NMDA- but not non
      NMDA-evoked adenosine release. Forskolin, but not 1,9-dideoxy-forskolin, produced
      a slight but significant increase in NMDA-evoked adenosine release, suggesting
      that the formation of cyclic AMP may somehow be involved. The inhibition of NMDA
      evoked adenosine release by IBMX is not accompanied by enhanced cyclic AMP
      recovery in superfusates, nor is release diminished when cyclic AMP transport is
      inhibited by probenecid, suggesting that the adenosine is not derived from the
      extracellular metabolism of released cyclic AMP. It is possible that 5'AMP,
      derived from the intracellular conversion of cyclic AMP by phosphodiesterase,
      might be released during NMDA receptor activation. However, more selective
      inhibitors of the specific phosphodiesterase isozymes known to be located in the
      cortex failed to diminish NMDA-evoked adenosine release. Therefore, the effects
      of both forskolin and IBMX on NMDA-evoked adenosine release could be nonspecific,
      coincidental and unrelated to their actions on cyclic AMP levels in the cortex.
      However, it is also possible that a novel IBMX-sensitive phosphodiesterase plays
      a primary role in converting cyclic AMP to 5'AMP intracellularly during NMDA
      receptor activation; the 5'AMP could then exit the cells and be converted to
      adenosine extracellularly.

PMID- 7530212
TI  - G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation:
      comparison of T cell depletion strategies using different CD34+ selection systems
      or CAMPATH-1.
AB  - Allogeneic transplantation of granulocyte colony-stimulating factor (G-CSF)
      mobilized peripheral blood progenitor cells (PBPC) appears to be an attractive
      alternative to allogeneic bone marrow transplantation (BMT). However, because
      vast amounts of potentially graft-vs.-host-reactive T cells are transfused with
      PBPC grafts, the use of PBPC in the allogeneic setting may be associated with an
      increased incidence or severity of graft-vs.-host disease (GVHD). To evaluate
      strategies for prevention of GVHD after PBPC allografting, we have studied T cell
      depletion (TCD) of G-CSF-mobilized PBPC samples harvested from six healthy donors
      and from five patients scheduled for autologous PBPC transplantation. Three
      approaches (CAMPATH-1 plus autologous complement [C], immunomagnetic CD34+ cell
      selection, and biotin-avidin-mediated CD34+ cell selection) were compared. TCD of
      PBPC samples with the monoclonal antibody (MAb) CAMPATH-1 plus autologous C
      resulted in a median elimination of 2.16 log CD3+ T cells, whereas 39% of CD56+
      natural killer (NK) cells and 56% of CD34+ progenitor cells were recovered. TCD
      by CD34+ cell selection with the Isolex (Baxter, Munich, Germany) or Ceprate
      (CellPro, Bothell, WA) devices achieved median depletions (Isolex vs. Ceprate) of
      4.04 vs. 3.12 log T cells and > 5 vs. 3.27 log NK cells while allowing the
      recovery of 36 vs. 27% CD34+ cells. The median purity of CD34+ cells in the final
      product was 1.7 (CAMPATH-1), 94 (Isolex), and 65% (Ceprate). We conclude that all
      methods tested effectively deplete T cells from PBPC preparations harvested from
      healthy donors. Whereas immunomagnetic CD34+ selection is most effective in terms
      of elimination of T cells, the less intensive T and NK cell depletions achieved
      with CAMPATH-1 might be advantageous with regard to retaining engraftment
      potential and graft-vs.-leukemia (GVL) activity of PBPC allografts.

PMID- 7530213
TI  - The combination of Steel factor and GM-CSF blocks apoptosis induced by retinoic
      acid and upregulates AP-1 in a human growth factor-dependent cell line.
AB  - The effects of hematopoietic growth factors were examined on the cellular action
      of retinoic acid (RA) using the human factor-dependent cell line, MO7e. Treatment
      of cells with Steel factor (SLF) plus granulocyte-macrophage colony-stimulating
      factor (GM-CSF) synergistically stimulated cell proliferation compared to that
      with each factor alone. This synergism was even greater in the presence of RA
      than in its absence. Treatment of cells with RA resulted in apoptotic cell death
      associated with internucleosomal DNA fragmentation in the presence of either SLF
      or GM-CSF. RA-induced apoptosis and DNA fragmentation were completely blocked by
      treating cells with SLF plus GM-CSF. Northern analysis showed that the inhibition
      of RA effects on MO7e cells by SLF plus GM-CSF treatment occurred without
      modulation of expression of RA receptor-alpha (RAR-alpha) gene. Furthermore, a
      higher amount of AP-1 complex was detected by electrophoretic mobility shift
      assays in a nuclear extract prepared from cells treated with SLF plus GM-CSF
      compared to those treated with each factor alone, while the level of RAR-complex
      remained similar in cells treated with SLF and/or GM-CSF. These data suggest an
      interaction in signaling pathways among different types of receptors that might
      be associated with the AP-1 complex.

PMID- 7530214
TI  - Role of protein kinase C in hepatic erythropoietin synthesis.

PMID- 7530215
TI  - Bronchoalveolar lavage immunoglobulin A and G and antiproteases correlate with
      changes in diffusion indices during the natural course of pulmonary sarcoidosis.
AB  - We wanted to determine whether cell populations and soluble components in
      bronchoalveolar lavage (BAL) could be useful in predicting the outcome of lung
      function and chest radiography in patients with untreated pulmonary sarcoidosis.
      Analysis of soluble proteins in BAL fluid, included the levels of immunoglobulins
      and the two major antiproteases, alpha 2-macroglobulin (alpha 2-M) and alpha 1
      protease inhibitor (alpha 1-PI), expressed as a relative coefficient of excretion
      (RCE). Thirty one nonsmoking patients with biopsy proven sarcoidosis, who
      remained untreated, had reassessment of lung function tests after 6-54 months
      (median 21 months). No correlation was observed between initial BAL data and
      changes in lung volumes and radiographic opacities. By contrast, the initial BAL
      immunoglobulin A and G (IgA and IgG) RCE correlated inversely with the change in
      transfer factor for carbon monoxide (TLCO) in the whole group and in patients
      with sarcoidosis of recent origin (estimated disease duration < 6 months). In the
      whole group and in patients with longstanding disease (estimated disease duration
      > 24 months, or radiographic Stage 4), the change in carbon monoxide transfer
      coefficient (KCO) correlated negatively with the initial alpha 1-PI RCE and
      positively with the initial helper to suppressor T-cell (T4/T8) ratio. By
      contrast, no significant difference in BAL cellular and protein data was found
      between patients with recent and longstanding sarcoidosis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 7530217
TI  - Rapamycin, FK506 and cyclosporin A inhibit human prolactin gene expression.
AB  - In this work we demonstrate that transcription of the human prolactin gene is
      inhibited by the immunosuppressants FK506 (IC50 = 25 nM), cyclosporin A (IC50 =
      190 nM) and rapamycin (IC50 = 25 nM). Whereas the effect of FK506 and cyclosporin
      A is specific for prolactin gene transcription, rapamycin has a more general
      effect on transcription and/or translation in pituitary cells. In view of recent
      work demonstrating the immunoactivating role of prolactin, these results suggest
      that inhibition of prolactin gene expression in the pituitary may contribute to
      the mechanism of action of immunosuppressants.

PMID- 7530218
TI  - Demonstration of non-linear detection in ELISA resulting in up to 1000-fold too
      high affinities of fibrinogen binding to integrin alpha IIb beta 3.
AB  - To clarify the question as to why different solid-phase assays yield different
      results in terms of interaction strength, we used fibrinogen binding to
      immobilized alpha IIb beta 3 integrin as a test system. A classical 'three step'
      enzyme-linked (ELISA), a 'two step' biotin enzyme-linked streptavidin and a 'one
      step' radioligand assay were compared under otherwise identical conditions. Only
      the last assay yielded binding constants comparable to earlier data by total
      internal reflection fluorescence microscopy while the other assays yielded
      apparent binding constants 5- to 1000-fold too high. These effects are explained
      by non-linearity of detection signals.

PMID- 7530216
TI  - A novel member of the TRAF family of putative signal transducing proteins binds
      to the cytosolic domain of CD40.
AB  - CD40 is a member of the tumor necrosis factor receptor (TNF-R) family that
      regulates B-lymphocyte proliferation, immunoglobulin class-switching, and
      apoptosis through poorly defined signal transduction mechanisms. Using a yeast
      two-hybrid method, cDNAs were obtained that encode a novel protein, CD40
      associated protein-1 (CAP-1), which binds specifically to the cytosolic domain of
      CD40 but not TNF-R1, TNF-R2, or Fas. The CAP-1 protein contains a C-terminal
      domain that shares strong amino acid sequence homology with a unique domain found
      recently in two putative signal transducing proteins that bind to the TNF-R2
      cytosolic tail, TRAF1 and TRAF2. This C-terminal region of CAP-1 was sufficient
      to mediate binding to CD40 and homodimerization of CAP-1 proteins. The N-terminal
      portion of CAP-1 contains a RING finger motif and three zinc finger-like domains
      similar to those found in several regulatory proteins that interact with DNA or
      RNA. CAP-1 thus represents a new member of a family of potential signal
      transducing proteins that contain a conserved domain (the TRAF domain), bind to
      the cytosolic regions of particular members of TNF-R family proteins, and that
      can form homo- and heterotypic dimers.

PMID- 7530219
TI  - Haemorrhagic-ischaemic lesions of the neonatal brain: correlation between
      cerebral visual impairment, neurodevelopmental outcome and MRI in infancy.
AB  - The relationship between the degree of cerebral visual impairment, established
      using the acuity card procedure, and the extent of neurological sequelae was
      assessed in 65 at-risk neonates in a prospective follow-up study. MRI and CT
      scans were performed in all infants with severe neurological sequelae. 11 of 12
      children with an acuity at or below the 10th centile at 18 months developed
      cerebral palsy: the underlying condition was extensive cystic leukomalacia in
      all. An acuity above the 10th centile was no guarantee of normal development, as
      10 out of 52 such infants developed cerebral palsy. MRI and CT scans showed that
      periventricular high signal intensity in the occipital area was a non-specific
      finding with regard to visual function. Extensive periventricular white matter
      loss and involvement of the striate/parastriate cortex was found in the most
      severely visually impaired infants.

PMID- 7530220
TI  - Atypical dominance for language in developmental dysphasia.
AB  - The authors report an association between developmental language disorder and
      acquired aphasia in a 13-year-old right-handed boy. Acquired aphasia was caused
      by a right-frontal abscess (crossed aphasia). It was non-fluent, with a disorder
      of auditory comprehension, an unusual feature of prerolandic lesions. This case
      shows that developmental language impairment can be associated not only with an
      atypical cerebral dominance, but also with unusual patterns of intrahemispheric
      specialization. The rapid and complete recovery of this boy's aphasia suggests
      that the cerebral plasticity for acquired lesions can be normal in such cases.

PMID- 7530221
TI  - [Coronary angiogenesis: role, modulation and prospects].

PMID- 7530222
TI  - Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in
      chorioallantoic fusion and placentation.
AB  - Vascular cell adhesion molecule-1 (VCAM-1) is expressed on vascular endothelium
      in a variety of inflammatory conditions and mediates leukocyte recruitment from
      blood into tissues. In this study we report a novel role for VCAM-1 in the
      formation of the umbilical cord and placenta during development. The murine VCAM1
      gene was disrupted by targeted homologous recombination, and a distinct phenotype
      was found in VCAM-1-deficient embryos. At 8.5 days of gestation, the allantois
      failed to fuse to the chorion, resulting in abnormal placental development and
      embryonic death within 1-3 days. In addition, a role for VCAM-1 in early
      placental formation after chorioallantoic fusion was observed. In a minority of
      VCAM-1-deficient embryos, the allantois was able to fuse with the chorion, but
      the allantoic mesoderm was abnormally distributed over the chorionic surface. A
      small number of VCAM-1-deficient embryos survived, presumably by circumventing
      the placentation defects. They became viable and fertile adult mice with lack of
      VCAM-1 expression, normal organs, and an elevated number of circulating blood
      mononuclear leukocytes.

PMID- 7530223
TI  - RNase E autoregulates its synthesis by controlling the degradation rate of its
      own mRNA in Escherichia coli: unusual sensitivity of the rne transcript to RNase
      E activity.
AB  - RNase E is a key regulatory enzyme that appears to control the principal pathway
      for mRNA degradation in Escherichia coli. Here, we show that RNase E represses
      its own synthesis by reducing the cellular concentration of the rne (RNase E)
      gene transcript. Autoregulation is achieved by modulating the longevity of this
      3.6-kb mRNA, whose half-life ranges from < 40 sec to > 8 min depending on the
      level of RNase E activity in the cell. Feedback regulation is mediated in cis by
      the 5'-terminal 0.44-kb segment of rne mRNA, which is sufficient to confer this
      property onto a heterologous transcript to which it is fused. Like the intact
      protein, an amino-terminal fragment of RNase E lacking 563 amino acid residues
      can act in trans to repress rne gene expression. Paradoxically, raising the rne
      gene copy number 21-fold in E. coli causes an unexpected reduction in the
      concentration of the full-length rne transcript, yet results in a small increase
      in RNase E protein production. These surprising phenomena are explained in terms
      of a model in which the degradation of this long and highly labile mRNA commences
      before elongation of the nascent transcript has been completed. In such
      circumstances, gene expression can be unusually sensitive to changes in mRNA
      stability.

PMID- 7530224
TI  - Characterisation by molecular cloning of two genes from Streptomyces verticillus
      encoding resistance to bleomycin.
AB  - Extracts of a bleomycin (Bm)-producing Streptomyces verticillus ATCC15003 were
      found to possess an acetyltransferase activity which inactivates Bm in the
      presence of acetyl coenzyme A. DNA fragments of S. verticillus were introduced
      into S. lividans by cloning and transformants selected for resistance to Bm.
      Deletion mapping and subcloning of a 6-kb DNA fragment showed the presence of two
      resistance determinants, blmA and blmB. The acetyltransferase activity was
      encoded by blmB; nucleotide sequence analysis identified an ORF consisting of 301
      amino acids (aa) proposed to be that of Bm acetyltransferase (Bat). S. lividans
      and Escherichia coli transformants harboring plasmids carrying blmB produced an
      acetyltransferase which modified and determined resistance to Bm and structurally
      related antibiotics; this resistance gene has potential as a selective marker in
      gene transfer studies. Nucleotide sequence analysis of blmA revealed an ORF
      encoding 122 aa that had significant sequence similarity to the gene encoding the
      Bm-binding protein (Shble) identified by Gatignol et al. [FEBS Lett. 230 (1988)
      171-175] in Streptoalloteichus hindustanus, the tallysomycin-producer. The blmA
      gene was expressed in E. coli and the resulting protein, like the Shble protein,
      prevents in vitro Bm-induced DNA breakage.

PMID- 7530225
TI  - Gene organization in the bleomycin-resistance region of the producer organism
      Streptomyces verticillus.
AB  - A nucleotide sequence of 7 kb is reported, encompassing two bleomycin-resistance
      (BmR-encoding) genes and five other open reading frames (ORFs) from the Bm
      producing organism Streptomyces verticillus ATCC 15003. The deduced ORFs, in
      sequence order, encode for (i) a protein homologous to an amino-acid dioxygenase;
      (ii) BlmA, the BmR-binding protein described by Sugiyama et al. [Gene 151 (1994)
      11-16]; (iii) a product containing three copies of a sequence homologous to the
      ankyrin repeat; (iv) a product lacking homology to any of the sequences in the
      Protein Identification Resource database (PIR), release 37; (v) BlmB, the BmR
      acetyltransferase described by Sugiyama et al. (1994); (vi) an unidentified
      protein which augmented resistance determined by ORF2 (BlmA); (vii) a member of
      the ATP-binding cassette (ABC) family of transport protein. Predicted
      translational frameshifts in the -1 frame occur at the junctions between ORF3 and
      ORF4, ORF4 and ORF5, and ORF6 and ORF7. Sequences homologous to ORF2 and ORF3
      were identified in the genome of the producer organism for the related antibiotic
      phleomycin.

PMID- 7530226
TI  - Commonly used cat reporter vectors contain a cAMP-inducible, cryptic enhancer
      that co-operates with NF-kappa B-sites.
AB  - Commercially available and widely used cat expression vectors were found to
      contain a forskolin (Fs)-inducible element capable of co-operation with NF-kappa
      B-sites in test promoters. An alternative NF-kappa B-dependent reporter system is
      presented that allows investigation of the effects of Fs and other agents that
      augment intracellular cyclic AMP.

PMID- 7530229
TI  - [A study on fixatives for the simultaneous histological estimation of the gastric
      mucous gel layer and mucous cells in rat gastric surface mucosa].
AB  - We examined the special characteristics of various kinds of fixatives and tried
      to find the most suitable method for simultaneous histological estimation of the
      mucous gel layer and mucous cells in rat gastric paraffin sections stained with
      Alcian blue (pH2.5)-periodic acid Schiff (AB-PAS). The tested fixatives were
      (group in parentheses): absolute ethanol at -80 degrees C (A), absolute methanol
      at -80 degrees C (B), Carnoy's solution (C), formalin-ethanol (D) and formalin
      Tyrode (E). The thickness of the mucous gel layer (ML) and the numbers of AB- and
      PAS-positive cells (AB cells, PAS cells) of both the fundic gland area (F. area)
      and pyloric gland area (P. area) were measured microscopically (x 200). ML in the
      F. area was found in the order of (A) > (B) > (C) > (D) = (E). AB cells were in
      the order of (A) > (E) > (B) > (C) > (D); and PAS cells were in the order of (B)
      > (A) > (E) > (C) > (D). Effects of various fixatives in the P. area showed the
      same trend as the F. area. Apart from above mentioned procedures, we observed the
      effects of ethanol at various temperatures: -80 degrees C, -25 degrees C, -4
      degrees C and 20 degrees C. ML, AB and PAS cells showed the highest level at -80
      degrees C. Moreover, to confirm that these fixatives retain the mucus, we
      evaluated the hexose and hexosamine contents contained in the fixative solution
      after fixation. As a result of various fixations, the hexose and hexosamine
      values in the fixative solution were the smallest for ethanol at -80 degrees C.
      In conclusion, ethanol at -80 degrees C was the most suitable fixative for
      histological estimation of mucous gel and mucous cells in rat gastric surface
      mucosa.

PMID- 7530227
TI  - The yeast FKS1 gene encodes a novel membrane protein, mutations in which confer
      FK506 and cyclosporin A hypersensitivity and calcineurin-dependent growth.
AB  - FK506 and cyclosporin A (CsA) are potent immunosuppressive agents that display
      antifungal activity. They act by blocking a Ca(2+)-dependent signal transduction
      pathway leading to interleukin-2 transcription. Each drug forms a complex with
      its cognate cytosolic immunophilin receptor (i.e., FKBP12-FK506 and cyclophilin
      CsA) which acts to inhibit the Ca2+/calmodulin-dependent protein phosphatase 2B,
      or calcineurin (CN). We and others have defined the Saccharomyces cerevisiae FKS1
      gene by recessive mutations resulting in 100-1000-fold hypersensitivity to FK506
      and CsA (as compared to wild type), but which do not affect sensitivity to a
      variety of other antifungal drugs. The fks1 mutant also exhibits a slow-growth
      phenotype that can be partially alleviated by exogenously added Ca2+ [Parent et
      al., J. Gen. Microbiol. 139 (1993) 2973-2984]. We have cloned FKS1 by
      complementation of the drug-hypersensitive phenotype. It contains a long open
      reading frame encoding a novel 1876-amino-acid (215 kDa) protein which shows no
      similarity to CN or to other protein phosphatases. The FKS1 protein is predicted
      to contain 10 to 12 transmembrane domains with a structure resembling integral
      membrane transporter proteins. Genomic disruption experiments indicate that FKS1
      encodes a nonessential function; fks1::LEU2 cells exhibit the same growth and
      recessive drug-hypersensitive phenotypes observed in the original fks1 mutants.
      Furthermore, the fks1::LEU2 allele is synthetically lethal in combination with
      disruptions of both of the nonessential genes encoding the alternative forms of
      the catalytic A subunit of CN (CNA1 and CNA2). These data suggest that FKS1
      provides a unique cellular function which, when absent, increases FK506 and CsA
      sensitivity by making the CNs (or a CN-dependent function) essential.

PMID- 7530228
TI  - Nitrinergic and peptidergic innervation of the human oesophagus.
AB  - The distribution, colocalisation, and interconnections of nitrinergic and
      peptidergic neurons and nerves in the human oesophagus were examined.
      Cryosections of surgically resected tissues from eight subjects were studied with
      indirect immunofluorescence for the presence of 11 neuropeptides and neuron
      specific enolase. After immunohistochemistry, nitric oxide synthase was shown on
      the same sections with the beta nicotinamide adenine dinucleotide phosphate
      (NADPH) diaphorase histochemical reaction. The histochemical findings were
      verified immunohistochemically on other sections with an antiserum against nitric
      oxide synthase. Most myenteric neurons (55%) were nitrinergic. Most (96%)
      received terminations positive for vasoactive intestinal polypeptide (VIP),
      calcitonin gene related peptide (CGRP) (80%), and galanin (59%). The neuronal
      somata of 14% also contained VIP, while 10% had galanin. Of the NADPH-diaphorase
      containing fibers seen in the muscle layers, many had closely associated VIP and
      galanin, but only rarely CGRP and substance P. Thus, despite abundant
      representation of both peptidergic and nitrinergic systems in oesophageal smooth
      muscle, only VIP and galanin colocalised to any significant extent with the
      nitrinergic elements. These findings provide morphological support for the role
      of nitric oxide as the non-adrenergic non-cholinergic inhibitory mediator in the
      human oesophagus and for its possible interactive role with the peptidergic
      system.

PMID- 7530230
TI  - The effect of exercise on basophil histamine release in patients with bronchial
      asthma.
AB  - There is increasing evidence for the role of basophils in allergic bronchial
      asthma. We studied the potential role of basophils in the pathogenesis of post
      exercise-induced bronchoconstriction by measuring the histamine release from
      basophils both spontaneously and following ConA, FMLP, anti-IgE and TPA
      treatment. Two groups of patients with allergic asthma were studied: group I
      consisted of 8 patients with an exercise-induced fall in FEV1 of 20% or more, and
      group II had 7 patients with bronchial asthma who had less than a 5% fall in FEV1
      following exercise. The mean spontaneous histamine release (SHR%) from basophils
      for group I was significantly larger than that of group II both before as well as
      at 5-10 and 60 min following exercise. The SHR% at baseline was 25 +/- 10 in
      group I (mean +/- SD) and 15 +/- 5 in group II (mean +/- SD). At 5-10 min
      following exercise it was 24 +/- 6 in group I and 11 +/- 2 in group II, while at
      60 min following exercise it was 24 +/- 6 in group I and 17 +/- 2 in group II.
      There was no significant difference between the two groups in the effect of ConA,
      FMLP, anti-IgE or TPA treatment on basophil histamine release. The enhanced
      bronchoconstriction by exercise did not affect histamine release either
      spontaneously or following those 4 stimuli. It was concluded that, although
      patients with exercise-induced asthma have a greater degree of spontaneous
      histamine release, this is not affected by induced bronchoconstriction, a finding
      which does not support a role for basophils in exercise-induced asthma.

PMID- 7530232
TI  - Lipid mediators of immune reactions: effect of a linked phosphorylserine group.
AB  - Immunoregulation by lipids containing the phosphorylserine (PHS) group has been
      studied in rodent peritoneal mast cells and human peripheral blood lymphocytes.
      When PHS is linked to a phospholipid backbone (mono- and diacylglycerol), mast
      cell activation is produced. However, the effect decreases linking the PHS group
      to long chain alkanols and is abolished in cholesteryl-PHS, showing that the
      acylglycerol moiety participates in mast cell activation. Phospholipids
      containing the PHS group inhibit proliferation of activated peripheral blood
      lymphocytes. In contrast to mast cells, this effect is retained in alkyl-PHS and
      is enhanced in cholesteryl-PHS, indicating that in this case the PHS group is the
      main effector. Among non-phospholipid PHSs, cholesteryl-PHS has been the most
      interesting since it associates lack of mast cell activation and high inhibitory
      activity on peripheral blood lymphocytes. This selectivity suggests that this
      compound may have a potential as an immunosuppressive agent.

PMID- 7530233
TI  - Inhibitory effect of calf fetuin on the cytotoxic activity of LAK cell-derived
      factors and tumor necrosis factor.
AB  - A protein-inhibiting LAK cell-mediated cytotoxicity was isolated from a LAK cell
      conditioned medium. The N-terminal amino acid sequence of this protein appeared
      to be identical to fetal calf fetuin. Pure isolated fetuin, as well as
      commercially available preparations of this protein, were shown to inhibit
      cytotoxic activity of both cytotoxic proteins released by LAK cells and TNF.

PMID- 7530234
TI  - Antibodies against linear and conformational epitopes of human papillomavirus
      type 16 that independently associate with incident cervical cancer.
AB  - In a seroepidemiological study of incident cervical cancer, 94 cases and 188
      population-based controls were used to evaluate the disease-association of IgG
      and IgA antibody responses against 6 human papillomavirus (HPV) type-16 antigens.
      Nine of the tested antibody responses were positively associated with cervical
      cancer, with odds ratios (ORs) ranging from 2.5 to 15.0. The antibody responses
      most strongly associated with cervical cancer were IgA against E6:10, an epitope
      derived from the carboxyterminal part of the HPV16 E6 [OR = 15.0, confidence
      intervals (CI) = 5.9-48.6], IgG against HPV16 virus-like particles (OR = 9.5, CI
      = 3.9-28.0) and IgG against the E1:19 epitope in the middle part of the E1
      protein of HPV16 (OR = 7.7, C1 = 3.9-16.5). When the 3 serological assays that
      showed the strongest association with cervical cancer were combined, positivity
      for 2 assays was found among 52% of cases at an OR of 29.9. We conclude that
      antibody responses to several linear and conformational HPV epitopes are
      independently associated with cervical cancer and that combined analysis of
      several HPV antibody responses can result in better predictive values for HPV
      associated cancer.

PMID- 7530236
TI  - E-selectin-mediated dynamic interactions of breast- and colon-cancer cells with
      endothelial-cell monolayers.
AB  - The molecular mechanisms involved in the dynamic interaction of human breast
      carcinoma cells with the endothelial cell lining of lymphatic vessels and post
      capillary blood venules are largely unknown. In the present study, laminar flow
      assays were used to investigate the ability of various normal breast cells and of
      breast- and colon-tumor cells to adhere to human umbilical cord endothelial cell
      monolayers. MCF-10A breast, MCF-7 and T-47D breast-carcinoma and clone A, RKO,
      and HT-29 colon-carcinoma cells accumulated and rolled, in the presence of flow,
      on tumor necrosis factor (TNF)-stimulated but not on unstimulated endothelial
      cell monolayers. Non-tumor and tumor cells continued to form transient adhesions
      with TNF-stimulated endothelial cells even when the flow rate was increased to
      levels found in arteries. Incubation of TNF-stimulated endothelial cells with an
      E-selectin-specific monoclonal antibody (MAb) partially or completely inhibited
      dynamic interactions and diminished adhesion strength, whereas integrin beta 1-
      and integrin alpha 6-specific MAbs had no effect. A set of highly invasive breast
      carcinoma cells (MDA-231, BT-549, HS-578t) neither adhered to nor rolled on
      resting or TNF-stimulated endothelial cell monolayers. However, after 5 min of
      static incubation, a fraction of these cells attached strongly to resting and TNF
      stimulated endothelial cells and this static adhesion could not be blocked by an
      E-selectin-specific monoclonal antibody. Our results suggest that E-selectin is a
      major homing receptor in the metastasis of some breast and colon cancers.

PMID- 7530231
TI  - Heterogenous nitrite production by IL-4-stimulated human monocytes and peripheral
      blood mononuclear cells.
AB  - The capacity of human peripheral blood mononuclear cells and monocytes to
      generate nitrites, spontaneously or in response to Interleukin-4 was evaluated in
      vitro. Peripheral blood mononuclear cells and monocytes were found to release
      significant amounts of nitrites after 8 to 12 days in culture. This spontaneous
      production of nitrites was inhibited in the presence of 1 mM NG monomethyl-L
      arginine, suggesting that this process was dependent upon the L-arginine
      metabolism. The present data also indicated that addition of Interleukin-4
      generally resulted in an increased nitrite production, that was potentiated by
      IFN-gamma, inactive alone. The response of human monocytes to Interleukin-4 was
      more heterogenous than that observed with unfractionated peripheral blood
      mononuclear cells. These results suggest that cell/cell interactions could play
      an important role in the activation of the nitric oxide synthase pathway in
      human.

PMID- 7530237
TI  - Comparison of immunohistochemistry and RT-PCR for detection of CD44v-expression,
      a new prognostic factor in human breast cancer.
AB  - In different human tumors, splice variants of the surface glycoprotein CD44
      (CD44v) are correlated with advanced stages of tumor growth and metastatic
      potential. In breast cancer and colon cancer, expression of epitopes encoded by
      exon v6 on primary tumors is an independent prognostic factor for poor patient
      survival. Two different screening methods for the detection of CD44 variants in
      tumors have been applied: immunohistochemistry (IHC) and semi-quantitative
      reverse transcription PCR (RT-PCR). In this study, we have compared the
      predictive capacity and the applicability of both approaches, using 31 human
      breast-tissue specimens (normal and neoplastic). IHC reveals lack of expression
      of CD44v on normal ductal epithelial cells but strong expression on myoepithelial
      cells. The majority of tumors express CD44 epitopes encoded by several variant
      exons. RT-PCR detects splice variants in normal epithelium, probably derived from
      RNA expressed in the myoepithelium. In tumors, RT-PCR reveals expression of a
      wide range of splice variants, including new ones that are not detected in normal
      breast tissue, e.g. ones that contain all variant exons. The conclusion of this
      comparison is that IHC is the better method for breast-tumor sample screening but
      that the increased sensitivity of RT-PCR can help to distinguish CD44v-positive
      from CD44v-negative tumors in cases where only a few tumor cells express variants
      or where epitopes are masked.

PMID- 7530235
TI  - Inhibition of TPA and 12(S)-HETE-stimulated tumor cell adhesion by prostacyclin
      and its stable analogs: rationale for their antimetastatic effects.
AB  - We have investigated the regulatory role of PGI2 and its stable analogs, i.e.,
      iloprost and cicaprost, on 12(S)-HETE- and TPA-enhanced tumor cell integrin
      expression and adhesion. Walker 256 carcinosarcoma cells express alpha IIb beta 3
      integrin receptors, which mediate their adhesion to endothelium, subendothelial
      matrix and fibronectin. Adhesion is enhanced by treatment with exogenous 12(S)
      HETE but not 12(R)-HETE or other lipoxygenase-derived hydroxy fatty acids, as
      well as by TPA. Both 12(S)-HETE and TPA enhanced alpha IIb beta 3 expression on
      W256 cells. PGI2 iloprost and cicaprost inhibited both 12(S)-HETE- and TPA
      enhanced adhesion to endothelium and subendothelial matrix as well as alpha IIb
      beta 3 expression on W256 cells. The mechanism responsible for the effect of PGI2
      was explored. Prostacyclin treatment of W256 cells resulted in an enhanced
      production of cAMP in a time- and dose-dependent manner. Pre-treatment of tumor
      cells with increasing concentrations of adenosine resulted in a dose-dependent
      decrease in the PGI2 effect on TPA or 12(S)-HETE-enhanced adhesion, suggesting
      that the PGI2 effect is mediated through PKA. Dibutyryl cAMP also blocked the
      12(S)-HETE- or TPA-enhanced adhesion, and adenosine pre-treatment did not result
      in an inhibition of the dibutyryl cAMP effect. Collectively, our results suggest
      that the cyclooxygenase metabolite PGI2 can antagonize the lipoxygenase
      metabolite 12(S)-HETE- and TPA-enhanced alpha IIb beta 3 expression and tumor
      cell adhesion via activation of adenylate cyclase and elevation of intracellular
      levels of cAMP.

PMID- 7530238
TI  - Shedding of the soluble form of CD30 from the Hodgkin-analogous cell line L540 is
      strongly inhibited by a new CD30-specific antibody (Ki-4).
AB  - The CD30-activation marker was detected as the Hodgkin-associated Ki-I antigen
      and is regarded as a target for the treatment of Hodgkin patients with
      immunotoxins. The CD30 is released from tumor cells and this soluble CD30 (sCD30)
      is an indicator of the disease activity. Since the shedding of sCD30 may be
      influenced by antibodies, we produced 6 new CD30-specific antibodies (Ki-2 to Ki
      7) for the purpose of finding antibodies that might inhibit the formation of
      sCD30. Ki-2 to Ki-7 and the other anti-CD30 antibodies Ki-I, Ber-H2, HeFi-I, M44,
      M67, HRS-I, HRS-4 and C10 were employed for epitope mapping. The binding of a
      particular radio-labeled anti-CD30 antibody to Hodgkin's-disease-derived L540
      cells was completed by addition of the various non-labeled anti-CD30 antibodies.
      Three non-overlapping regions, expressing different antigen-specific
      determinants, could be defined on the extracellular part of the CD30 molecule.
      Cluster A of determinants was recognized by Ki-2, Ki-4, Ki-6 and Ki-7, Ber-H2,
      HRS-I and HRS-4, while cluster B was detected by Ki-I, Ki-5 and M67. Cluster C,
      which probably contains the binding site for the CD30 ligand, was defined by Ki
      3, M44, HeFi-I and C10. Co-culture experiments of L540 cells with the various
      antibodies followed by the isolation of sCD30 from culture supernatant fluids
      revealed that the release of sCD30 was most strongly increased by Ki-I and weakly
      enhanced by Ki-2, Ki-3, Ki-5 and HeFi-I, whereas it was almost completely
      inhibited by Ki-4 and to a slightly lesser extent by Ber-H2.

PMID- 7530239
TI  - Induction of ICAM-1 and LFA-3 by Tax1 of human T-cell leukemia virus type 1 and
      mechanism of down-regulation of ICAM-1 or LFA-1 in adult-T-cell-leukemia cell
      lines.
AB  - The present study was undertaken to determine the role of HTLV-I TaxI in the up
      regulation of ICAM-I and LFA-3 in human T cells transformed with HTLV-I and the
      mechanism of down-regulation of ICAM-I and LFA-I in ATL-derived cell lines.
      Induction of TaxI in a human T-cell line Jurkat carrying the TaxI gene under the
      metallothionein promoter led to increases in mRNA and surface expression of ICAM
      I. The response of LFA-3 to TaxI induction was, on the other hand, relatively
      slow and weak, and might be indirect. Transactivation of the ICAM-I promoter by
      TaxI was further shown by co-transfection of a CAT reporter construct with the
      ICAM-I promoter and a plasmid expressing TaxI. The mechanism of down-regulation
      of ICAM-I or LFA-I in 4 ATL cell lines was next examined. ICAM-I mRNA was quite
      low in MT-I, but no genomic changes were found. The CAT reporter with the ICAM-I
      promoter was inactive in MT-I. Finally, combined treatment of MT-I with 5
      azacytidine and IFN-gamma induced re-expression of ICAM-I. Collectively, (a)
      transcriptional factor(s) necessary for expression of ICAM-I gene may be
      repressed in MT-I through DNA methylation. Three other ATL cell lines (TL-OmI,
      H582, HuT102) were found to have little mRNA for the LFA-I beta chain (CD18).
      H582 and HuT102 were also negative for the LFA-I alpha chain (CDIIa) mRNA. No
      genomic changes were found, and a CAT reporter gene with the CD18 promoter was
      inactive in the 3 of them, again suggesting lack of (a) transcriptional factor(s)
      necessary for CD18 expression.

PMID- 7530242
TI  - Multi-resistance isolates possessing characteristics of both Burkholderia
      (Pseudomonas) cepacia and Burkholderia gladioli from patients with cystic
      fibrosis.
AB  - Multi-resistant strains from three UK centres, previously identified as
      Burkholderia (formerly Pseudomonas) cepacia, and associated with morbidity,
      mortality and transmission among patients with cystic fibrosis have been further
      characterised. Biochemical tests and fatty acid analyses indicate these strains
      to possess some characteristics atypical of B. cepacia but bearing close
      resemblance to Burkholderia gladioli, an organism previously regarded solely as a
      plant pathogen and a hindrance to the identification of B. cepacia. In contrast
      to the majority of reference strains, all multi-resistant clinical isolates
      possessed rough lipopolysaccharide which may be a major factor responsible for
      their increased antibiotic resistance and virulence. In view of the potential
      clinical and social problems in CF patients posed by these multi-resistant
      strains, it would seem prudent to consider the isolation of either B. cepacia or
      B. gladioli as of equal significance.

PMID- 7530240
TI  - Expression of CD44 variant isoforms in normal and neoplastic cells of the lung.
AB  - CD44 is a cell surface receptor that has been implicated in lymphocyte homing,
      hematopoiesis, cell migration and possibly also tumor metastasis. In the present
      study, expression of CD44 variant (CD44v) isoforms was analyzed in 23 lung cancer
      specimens together with corresponding normal lung tissues by Southern blot
      analysis coupled with reverse transcription-polymerase chain reaction
      amplification. We found that CD44v isoforms were expressed in all lung cancer
      specimens, suggesting a possible role in the establishment of metastases by these
      highly malignant tumors, but normal tissues were also positive. This is in marked
      contrast to the previous reports of essentially negligible expression of CD44v
      isoforms in normal colon and breast, and suggests a physiological function in the
      lung.

PMID- 7530241
TI  - Clinical usefulness of CYFRA assay in diagnosing lung cancer: measurement of
      serum cytokeratin fragment.
AB  - We evaluated the diagnostic usefulness of measurement of the soluble cytokeratin
      19 fragment, a new tumor marker, in 391 patients with lung cancer and in 424
      patients with benign lung diseases. Serum concentrations of cytokeratin 19
      fragment were measured by a sandwich ELISA (CYFRA). The cut-off value was defined
      as 3.5 ng/ml, which is associated with a specificity of 85% for benign lung
      diseases. CYFRA had a high sensitivity (57.5%) in all subjects with lung
      carcinoma, and had a higher sensitivity for squamous cell carcinoma (73.1%, n =
      141) than squamous cell carcinoma-related antigen (61.0%). CYFRA was associated
      with a relatively high sensitivity (42.1%) in early-stage squamous cell carcinoma
      (stage I, based on the classification of the Japan Lung Cancer Society), but the
      CYFRA titer was higher in advanced squamous cell carcinoma than in early-stage
      squamous cell carcinoma. Our findings suggest that CYFRA is potentially useful
      for diagnosis and monitoring of lung carcinoma, especially for squamous cell
      carcinoma.

PMID- 7530243
TI  - Are all carbapenems created equal?

PMID- 7530244
TI  - Cystic fibrosis transmembrane conductance regulator is required for protein
      kinase A activation of an outwardly rectified anion channel purified from bovine
      tracheal epithelia.
AB  - Our laboratory has developed a protocol for the isolation of a 140-kDa protein
      that forms an anion-selective channel when reconstituted into planar lipid
      bilayers. Polyclonal antibodies have been raised against the 38-kDa component of
      this purified protein. This channel has a linear current-voltage relationship and
      is not activated by protein kinase A (PKA) plus ATP. Using the same antibody and
      a modified purification protocol (eliminating the ion exchange chromatography
      steps), we isolated and reconstituted two other anion channels from tracheal
      membrane vesicles. In vitro phosphorylation of these isolated proteins by PKA and
      ATP revealed four bands migrating at 52, 85, 120, and 174 kDa.
      Immunoprecipitation experiments with anti-CFTR antibodies indicate that the 174
      kDa phosphoprotein was CFTR. Upon incorporation of these isolated proteins into
      planar bilayers, an anion channel that exhibited a marked outward rectification
      in symmetrical Cl- solutions with a slope conductance of 82 pS at depolarizing
      voltages was observed. PKA and ATP increased channel activity but only from one
      side of the bilayer. However, channel activity was unaffected by addition of ATP
      alone from either side of the membrane. DIDS (100 microM) applied to the opposite
      side of the bilayer to which PKA and ATP act, blocked channel activity. A linear
      anion-selective channel with a conductance of 16 pS could be also resolved after
      inhibition of the outwardly rectified anion channel by DIDS in the presence of
      PKA and ATP. This small conductance channel was inhibited by 300 microM
      diphenylamine-2-carboxylic acid. Immunodepletion of the 174-kDa phosphoprotein
      from the preparation prevented activation of the 82-pS outwardly rectified anion
      channel by PKA and ATP. However, the PKA-dependent in vitro phosphorylation of
      the 52-, 85-, and 120-kDa phosphoproteins was unaffected by the absence of CFTR.
      Our results suggest a direct regulatory relationship between an outwardly
      rectified anion channel and CFTR.

PMID- 7530246
TI  - The two nucleotide-binding domains of cystic fibrosis transmembrane conductance
      regulator (CFTR) have distinct functions in controlling channel activity.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel
      contains two cytoplasmic nucleotide-binding domains (NBDs). After phosphorylation
      of the R domain, ATP interacts with the NBDs to regulate channel activity. To
      learn how the NBDs regulate channel function, we used the patch-clamp technique
      to study CFTR and variants which contained site-directed mutations in the
      conserved Walker A motif lysine residues in either NBD1 (K464A), NBD2 (K1250A and
      K1250M), or both NBDs simultaneously (K464A/K1250A). Studies in related proteins
      suggest that such mutations slow the rate of ATP hydrolysis. These mutations did
      not alter the conductive properties of the channel or the requirement for
      phosphorylation and ATP to open the channel. However, all mutations decreased
      open state probability. Mutations in NBD1 decreased the frequency of bursts of
      activity, whereas mutations in NBD2 and mutations in both NBDs simultaneously
      prolonged bursts of activity, as well as decreased the frequency of bursts. These
      results could not be attributed to altered binding of nucleotide because none of
      the mutants studied had reduced 8-N3ATP binding. These data suggest that the two
      NBDs have distinct functions in channel gating; ATP hydrolysis at NBD1 initiates
      a burst of activity, and hydrolysis at NBD2 terminates a burst.

PMID- 7530247
TI  - Characteristics of the nitric oxide synthase-catalyzed conversion of arginine to
      N-hydroxyarginine, the first oxygenation step in the enzymic synthesis of nitric
      oxide.
AB  - The nitric oxide synthase-catalyzed conversion of L-arginine to L-citrulline and
      nitric oxide is known to be the sum of two partial reactions: oxygenation of
      arginine to N-hydroxyarginine, followed by oxygenation of N-hydroxyarginine to
      citrulline and nitric oxide. Whereas the conversion of N-hydroxyarginine to
      citrulline and nitric oxide has been the subject of a number of studies, the
      oxygenation of arginine to N-hydroxyarginine has received little attention. Here
      we show that substrate amounts of rat cerebellar nitric oxide synthase, in the
      absence of added NADPH, catalyze the conversion of arginine to N-hydroxyarginine
      as the dominant product. The product appears not to be tightly bound to the
      enzyme. A maximum of 0.16 mol of N-hydroxyarginine/mol of nitric oxide synthase
      subunit was formed. The reaction requires oxygen and the addition of
      Ca2+/calmodulin and is stimulated 3-fold by tetrahydrobiopterin. Upon addition of
      NADPH, citrulline is formed exclusively. Conversion of N-hydroxyarginine to
      citrulline, like the first partial reaction, requires Ca2+/calmodulin and is
      stimulated by tetrahydrobiopterin but differs from the first partial reaction in
      being completely dependent upon addition of NADPH. These results indicate that
      brain nitric oxide synthase contains an endogenous reductant that can support
      oxygenation of arginine but not of N-hydroxyarginine. The reductant is not NADPH,
      since the amount of nitric oxide synthase-bound NADPH is appreciably less than
      the amount required for N-hydroxyarginine synthesis. Possible candidates for this
      role are discussed in relation to proposed mechanisms of action of nitric oxide
      synthase.

PMID- 7530249
TI  - Structural and functional studies of the intracellular tyrosine kinase MATK gene
      and its translated product.
AB  - We recently cloned the cDNA which encodes a novel megakaryocyte-associated
      tyrosine kinase termed MATK. In this study, we have cloned and characterized the
      human MATK gene as well as the murine homolog of human MATK cDNA and performed
      functional studies of its translated product. Comparison of the deduced amino
      acid sequences of human and murine MATK cDNAs revealed 85% homology, indicating
      that MATK is highly conserved in mouse and human. The human gene consists of 13
      exons interrupted by 12 introns. The genetic units which encode the SH3 and SH2
      domains are located on separate exons. The putative ATP binding site (GXGXXG) is
      localized on exon 7, and the entire catalytic domain is subdivided into seven
      exons (7-13). Somatic cell hybrid analysis indicated that human MATK gene is
      located on chromosome 19 while the murine Matk gene is located on chromosome 10.
      The immediate 5'-flanking region was highly rich in GC sequences, and potential
      cis-acting elements were identified including several SP1, GATA-1, APRE, and
      APRE1. Antisense oligonucleotides directed against MATK mRNA sequences
      significantly inhibited megakaryocyte progenitor proliferation. Functional
      studies indicated that MATK can phosphorylate the carboxyl-terminal conserved
      tyrosine of the Src protein. These results support the notion that MATK acts as a
      regulator of p60c-src in megakaryocytic cells and participates in the pathways
      regulating growth of cells of this lineage.

PMID- 7530245
TI  - Inorganic cation dependence of putrescine and spermidine transport in human
      breast cancer cells.
AB  - The mechanism of polyamine uptake in mammalian cells is still poorly understood.
      The role of inorganic cations in polyamine transport was investigated in ZR-75-1
      human breast cancer cells. Although strongly temperature dependent, neither
      putrescine nor spermidine uptake was mediated by a Na+ cotransport mechanism. In
      fact, Na+ and cholinium competitively inhibited putrescine uptake relative to
      that measured in a sucrose-based medium. On the other hand, ouabain, H+, Na+, and
      Ca2+ ionophores, as well as dissipation of the K+ diffusion potential, strongly
      inhibited polyamine uptake in keeping with a major role of membrane potential in
      that process. Polyamine transport was inversely dependent on ambient osmolality
      at near physiological values. Putrescine transport was inhibited by 70% by
      decreasing extracellular pH from 7.2 to 6.2, whereas spermidine uptake had a more
      acidic optimum. Deletion of extracellular Ca2+ inhibited putrescine uptake more
      strongly than chelation of intracellular Ca2+. In fact, bound divalent cations
      were absolutely required for polyamine transport, as shown after brief chelation
      of the cell monolayers with EDTA. Either Mn2+, Ca2+, or Mg2+ sustained putrescine
      uptake activity with high potency (Km = 50-300 microM). Mn2+ was a much stronger
      activator of spermidine than putrescine uptake, suggesting a specific role for
      this metal in polyamine transport. Other transition metals (Co2+, Ni2+, Cu2+, and
      Zn2+) were mixed activators/antagonists of carrier activity, while Sr2+ and Ba2+
      were very weak agonists, while not interfering with Ca2+/Mg(2+)-dependent
      transport. Thus, polyamine uptake in human breast tumor cells is negatively
      affected by ionic strength and osmolality, and is driven, at least in part, by
      the membrane potential, but not by the Na+ electrochemical gradient. Moreover,
      the polyamine carrier, or a tightly coupled accessory component, appears to have
      a high-affinity binding site for divalent cations, which is essential for the
      uptake mechanism.

PMID- 7530248
TI  - Involvement of alpha v beta 3 integrin in mediating fibrin gel retraction.
AB  - Platelet integrin alpha IIb beta 3 (GPIIb-IIIa) plays important roles in platelet
      mediated clot retraction. However, little is known about the mechanisms of clot
      retraction mediated by nucleated cells. In this report, we demonstrate that
      another member of the beta 3 integrin family, alpha v beta 3, is involved in clot
      retraction mediated by nucleated cells. Retraction of fibrin clots was observed
      using a human melanoma cell line, C32TG, which contains no alpha IIb beta 3
      complex. This retraction was inhibited by RGD-containing peptide, monoclonal anti
      beta 3, and anti-alpha v beta 3 antibodies. Immunoelectron microscopic studies
      revealed a direct interaction between beta 3 integrin and fibrin fibers at an
      early stage of clot retraction. We found that another human embryonal cell line,
      293, which is known to express alpha v beta 1, but no alpha v beta 3, lacks
      fibrin gel retractile activity. Upon transfection of beta 3 DNA into 293 cells,
      the beta 3 subunit formed a complex with an endogenous alpha v subunit. The beta
      3-bearing transfectants were found to retract fibrin gels, which was specifically
      inhibited by anti-beta 3 antibody. In addition, a point mutation at Asp119 in the
      beta 3 ligand binding domain abolished the clot retractile activity of 293
      transfectants, indicating the requirement of alpha v beta 3 ligand-binding
      activity. Our findings suggest that alpha v beta 3 is involved in mediating the
      interaction between the three-dimensional fibrin network and nucleated cells and
      in promoting "post-receptor occupancy" events.

PMID- 7530250
TI  - Molecular cloning and characterization of an aquaporin cDNA from salivary,
      lacrimal, and respiratory tissues.
AB  - The Aquaporin family of water channels plays a fundamental role in transmembrane
      water movements in numerous plant and animal tissues. Since the molecular pathway
      by which water is secreted by salivary glands is unknown, a cDNA was isolated
      from rat submandibular gland by homology cloning. Similar to other Aquaporins,
      the salivary cDNA encodes a 265-residue polypeptide with six putative
      transmembrane domains separated by five connecting loops (A-E); the NH2- and COOH
      terminal halves of the polypeptide are sequence-related, and each contains the
      motif Asn-Pro-Ala. A mercurial-inhibition site is present in extracellular loop
      E, and cytoplasmic loop D contains a cAMP-protein kinase phosphorylation
      consensus. In vitro translation yielded a 27-kDa polypeptide, and expression of
      the cRNA in Xenopus oocytes conferred a 20-fold increase in osmotic water
      permeability (Pf) which was reversibly inhibited by 1 mM HgCl2. Northern analysis
      demonstrated a 1.6-kilobase mRNA in submandibular, parotid, and sublingual
      salivary glands, lacrimal gland, eye, trachea, and lung. In situ hybridization
      revealed a strong hybridization over the corneal epithelium in eye and over the
      secretory lobules in salivary glands. These studies have identified a new
      mammalian member of the Aquaporin water channel family (gene symbol AQP5) which
      is implicated in the generation of saliva, tears, and pulmonary secretions.

PMID- 7530251
TI  - Chinese hamster ovary cells expressing a novel type of acetylated low density
      lipoprotein receptor. Isolation and characterization.
AB  - Macrophage scavenger receptors mediate the recognition of a wide range of
      negatively charged macromolecules including acetylated low density lipoproteins
      (AcLDL). Chinese hamster ovary (CHO) cells were cultured in the presence of
      increasing concentrations of simvastatin, a cholesterol biosynthesis inhibitor,
      and AcLDL as the sole source of exogenous lipoproteins. The cells surviving under
      these conditions specifically bound 125I-labeled AcLDL with high affinity and
      degraded them via an endocytic pathway. Unexpectedly, the association and
      degradation of 125I-labeled AcLDL by these CHO cells were not inhibited by
      dextran sulfate, fucoidan, and polyinosinic acid, competitors of macrophage
      scavenger receptors, but were completely inhibited by maleylated bovine serum
      albumin. Furthermore, these cells effectively took up negatively charged
      liposomes containing acidic phospholipids such as phosphatidylserine and
      phosphatidic acid, whereas CHO cells expressing macrophage scavenger receptors
      did not. AcLDL and negatively charged liposomes were cross-competed with each
      other. Northern blot analysis using the cDNA for the macrophage scavenger
      receptor revealed that these CHO cells did not express this receptor. From these
      observations, we conclude that the isolated CHO cells express a novel type of
      AcLDL receptor, which is distinct from macrophage scavenger receptors with
      respect to ligand specificity and competitor sensitivity.

PMID- 7530254
TI  - Regulation of insulin-like growth factor (IGF)-binding protein-4 availability in
      normal human osteoblast-like cells: role of endogenous IGFs.
AB  - Insulin-like growth factor-binding protein-4 (IGFBP-4) is an important regulator
      of insulin-like growth factor-I (IGF-I) anabolic activity in bone. Although
      cultured human osteoblast-like (hOB) cells have been reported to secrete IGFBP-4,
      we could not detect IGFBP-4 protein in 8 of 27 individual donor-derived hOB-cell
      conditioned medium (hOB-CM) samples examined by Western ligand blotting.
      Nonetheless, this subset of hOB cells had normal IGFBP-4 messenger ribonucleic
      acid expression and protein secretion. Regulation of IGFBP-4 levels in hOB
      cultures appeared to occur extracellularly. hOB cells produce an IGFBP-4
      proteinase that requires the presence of IGF for cleavage of the IGFBP-4 molecule
      into 2 fragments of approximately 18 and 14 kilodaltons. These fragments are not
      detected by Western ligand blotting. Our data indicate that elevated endogenous
      levels of IGF can activate IGFBP-4 proteolysis, because in hOB cultures lacking
      detectable IGFBP-4 protein 1) basal IGF messenger ribonucleic acid expression was
      increased; 2) IGF-II peptide levels were elevated; 3) IGF-neutralizing antibodies
      added to hOB-CM attenuated the proteolysis of exogenous IGFBP-4; and 4)
      recombinant human IGFBP-4 was proteolyzed into 2 immunoreactive fragments of
      approximately 18 and 14 kilodaltons during cell-free incubations in these hOB-CM
      without the addition of exogenous IGF. In conclusion, elevated IGF expression and
      secretion can contribute to enhanced proteolysis of endogenous and exogenous
      IGFBP-4 via a proteinase secreted by cultured hOB cells. Levels of endogenous IGF
      peptide may determine IGFBP-4 availability in the bone microenvironment and,
      thus, modulate the local cell response to IGF-I.

PMID- 7530253
TI  - Identification of the major sites of phosphorylation in IGF binding protein-3.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is the major carrier of
      insulin-like growth factor I and II in the circulation. IGFBP-3 is secreted by
      various tissues and cell lines as a glycosylated phosphoprotein. We have
      identified two major serine phosphorylation sites located at amino acids 111 and
      113 of the human protein. These serine residues and neighboring amino acids
      potentially involved in defining a protein kinase recognition sequence were
      mutated to alanine using PCR. Single and double point mutants were stably
      transfected into CHO-cells and analyzed for their level of phosphorylation.
      Mutation of both serines reduced phosphorylation by > 80% in the full-length
      protein and completely abolished phosphorylation in a 17 kDa IGFBP-3 fragment,
      derived from digestion with EndoProteinase Lys-C. The 17 kDa fragment contained
      serines 111 and 113. S111A/S113A, a double serine-to-alanine mutant at positions
      111 and 113, showed a strongly reduced glycosylation pattern that appears to be
      the result of amino acid substitutions rather than lack of phosphorylation.
      Mutant S111A/S113A, despite being non-phosphorylated and non-glycosylated, is
      functionally similar to the wild-type IGFBP-3 in terms of IGF-I binding. These
      results enhance our understanding on the functional role of glycosylation and
      phosphorylation of IGFBP-3.

PMID- 7530252
TI  - Evaluation of three new hydrocolloid dressings: retention of dressing integrity
      and biodegradability of absorbent components attenuate inflammation.
AB  - Residues from hydrocolloid dressings (HCDs) that originate from matrix
      disintegration and nonbiodegradability of the absorbent components, may cause
      deep-seated, unresolved inflammation in tissue that appears otherwise healed. The
      purpose of this study was to evaluate three new HCDs that were formulated with
      the goal of attenuating the inflammatory responses that may arise from HCD
      therapy. Two of the HCDs (A-106 and A-107) consisted of conventional absorbents
      dispersed in a new maceration-resistant adhesive matrix. The same matrix, mixed
      with potentially biodegradable dextran microspheres, formed the third dressing
      (Dextran Bead Dressing [DBD]). In this pilot scale study these novel dressings
      were evaluated on full-thickness dermal wounds on swine. Restore (Hollister) and
      DuoDERM CGF (Convatec) dressings were used as controls. Wound healing was
      evaluated histomorphometrically. Pertinent histologic parameters were ranked from
      wound tissue that was harvested 18 days after wounding. Grossly visible dressing
      disintegration ranged from minimal (DBD) to severe (Restore). Disintegration of
      other dressings was moderate. The percentage of tissue sections exhibiting giant
      cells reflected, in parallel, the observed extent of dressing disintegration.
      Thirty-eight percent of wounds dressed with DBD contained giant cells; 74 and
      100% of wounds treated with DuoDERM CGF and Restore, respectively, contained
      giant cells. DBD-dressed wounds had relatively fewer chronic inflammatory cells
      than other dressings. These wounds were also characterized by a well-organized
      collagen matrix and complete reepithelialization. The extent of wound closures
      was similar for all dressing types except Restore. Closure of Restore-dressed
      wounds was delayed compared with closure with DBD and DuoDERM CGF on all days of
      evaluation except one. A-106 and A-107 were comparable to DuoDERM CGF in
      retention of dressing integrity and the elicited inflammatory tissue response.
      The DBD dressing appears to possess equivalent properties of typical HCDs while
      causing minimal tissue reactions.

PMID- 7530256
TI  - Changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3, growth
      hormone (GH)-binding protein, erythrocyte IGF-I receptors, and growth rate during
      GH treatment.
AB  - To assess the relative determinants of growth rate, we measured serum levels of
      insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), and GH
      binding protein (GHBP) as well as IGF-I erythrocyte receptor specific binding
      (SB) in 14 prepubertal GH-deficient children before and during the first year of
      treatment with 0.043 mg/kg.day GH. Serum IGF-I and IGFBP-3 levels, measured by
      RIA, were significantly increased by 2 weeks and showed progressive increases
      throughout the year of GH therapy. Growth rate (height velocity SD score adjusted
      for bone age) correlated best with the 12 month changes in IGFBP-3 (r = 0.81; P <
      0.001) and IGF-I (r = 0.72; P = 0.005), and to a lesser extent with the 12 month
      absolute IGFBP-3 (r = 0.58; P = 0.04) and the 6 month change in IGFBP-3 (r =
      0.55; P = 0.05). The baseline IGF-I correlated inversely with the growth rate
      during GH therapy (r = -0.55; P = 0.05) and was the best pretreatment predictor
      of growth response. GHBP, as measured by ligand-mediated immunofunctional assay,
      showed no significant change during GH therapy and did not correlate with growth
      response. The baseline GHBP, however, did correlate with both the 12 month IGFBP
      3 (r = 0.72; P = 0.006) as well as the 2 week change in IGFBP-3 (r = 0.63; P =
      0.05). Erythrocyte IGF-I SB showed a significant decrease by 6 months secondary
      to a decrease in IGF-I receptor number, with no change in affinity. The 6 month
      IGF-I receptor binding correlated inversely with the increase in IGF-I (r = 
      0.88; P < 0.001). Erythrocyte IGF-I SB at baseline did not correlate with the
      growth response, although there was an inverse trend between the 6 month IGF-I
      receptor level and the growth rate. IGF-I and IGFBP-3 show progressive increases,
      whereas the erythrocyte IGF-I receptor-binding capacity decreases by 6 months,
      and GHBP shows little change during the first year of GH treatment. Data from
      this study suggest that changes in IGFBP-3 and, to a lesser extent, IGF-I are the
      major correlates of growth rate, and that down-regulation of the IGF-I receptor
      may have relatively little influence on growth rate compared with changes in
      IGFBP-3 and IGF-I.

PMID- 7530255
TI  - Association of Graves' disease with an allele of the interleukin-1 receptor
      antagonist gene.
AB  - The proinflammatory cytokine, interleukin-1 (IL-1), has been implicated in the
      pathogenesis of several autoimmune and inflammatory diseases. One of its natural
      inhibitors, IL-1 receptor antagonist, is a potent antiinflammatory agent. We have
      previously described genetic associations between an allele of the IL-1 receptor
      antagonist gene (IL1RN*2) and several autoimmune and inflammatory diseases. In
      the present study, we tested the association of this polymorphism with thyroid
      diseases. We genotyped 2 separate cohorts (total of 100 patients) with Graves'
      disease and 58 patients with Hashimoto's thyroiditis and compared IL1RN*2
      frequencies with those in 261 ethnically matched controls. There was a
      significant increase in IL1RN*2 frequency and carriage rate in Graves' disease,
      but this was not associated with thyroid antibody levels, T4 levels, thyroid
      associated ophthalmopathy, or outcome after antithyroid drug treatment. In
      contrast, there was no difference in the frequency of IL1RN*2 between patients
      with Hashimoto's thyroiditis and the control group. Whether the IL1RN
      polymorphism makes a direct functional contribution to the pathogenesis of
      Graves' disease or is acting as a marker for a linked gene is being investigated.

PMID- 7530258
TI  - Human luteal cells express leukocyte functional antigen (LFA)-3.
AB  - Leukocyte functional antigen-3 (LFA-3)/cluster of differentiation-58 (CD-58)
      antigen is known as a ligand for CD-2 antigen, which is a specific surface marker
      of T-lymphocytes. To investigate the involvement of T-lymphocytes on corpus
      luteum (CL) function, the expression of LFA-3 in human CL was examined by the
      indirect immunofluorescence method with frozen sections. LFA-3 was not detected
      on the granulosa cells of primordial, primary, or atretic follicles, but was
      weakly expressed on the granulosa cells of growing and preovulatory follicles.
      After ovulation, LFA-3 was clearly expressed on large luteal cells of the CL in
      any stage of the luteal phase, and the highest expression was observed in the
      midluteal phase. Antigen expression was also observed in the large luteal cells
      in CL of pregnancy. Human granulosa cells were isolated from the patients who had
      undergone in vitro fertilization treatment and were cultured in vitro with or
      without hCG (1 IU/mL), tumor necrosis factor-alpha (TNF alpha; 10 ng/mL), or
      interleukin-1 alpha (10 ng/mL). By the indirect immunofluorescence method, LFA-3
      was detected on granulosa cells after culture for 1 day, although the
      fluorescence intensity was very weak. LFA-3 was clearly detected on granulosa
      cells after 7 days of culture, especially on those with TNF alpha. Flow
      cytometrical analysis with 7-day cultured cells showed that the percent
      positivity of LFA-3-positive granulosa cells cultured with TNF alpha was
      significantly higher than that of the controls (without treatment; 66.5 +/- 3.7%
      vs. 34.3 +/- 4.9%; P < 0.01; n = 7). The percent positivity of cells cultured
      with interleukin-1 alpha was slightly higher (51.5 +/- 4.5%; P < 0.1) than that
      of the controls, whereas treatment with hCG caused no significant difference
      (46.6 +/- 4.7%) from the controls. These findings indicate that LFA-3 is a
      differentiation antigen of human granulosa cells. They also suggest that large
      luteal cells can interact, through LFA-3 molecules, with the CD-2 antigen
      positive T-lymphocytes invading the CL after ovulation, and that the expression
      of LFA-3 is under the control of some cytokines, including TNF alpha.

PMID- 7530257
TI  - Serum insulin-like growth factor-binding protein-3 (IGFBP-3) levels and IGFBP-3
      protease activity in normal, abnormal, and multiple human pregnancy.
AB  - Proteolytic activity directed against insulin-like growth factor (IGF)-binding
      protein-3 (IGFBP-3) is found in human pregnancy serum. We have investigated
      changes in this protease activity in pregnancies in which the fetus is small for
      gestational age and in multiple pregnancies. Maternal serum was obtained from 18
      singleton pregnancies at 27 weeks gestational age (GA), and matched fetal serum
      was collected by cordocentesis. Fetuses were appropriate for GA (AGA; n = 6),
      small for gestational age (SGA) with evidence of uteroplacental insufficiency
      (UPI; starved SGA; n = 6), or SGA without UPI (nonstarved SGA; n = 6). In a
      second study, serum was obtained from women with singleton (n = 10), twin (n =
      10), and higher multiple pregnancies (n = 10) at 9 weeks GA. All women with more
      than three fetuses underwent embryo reduction to 2 fetuses before 15 weeks
      gestation, when a second serum sample was obtained. Circulating IGF-I and IGF-II
      were measured by RIA, and IGFBP-3 was measured by both RIA and immunoradiometric
      assay. IGFBP-3 protease activity was assessed by Western ligand blotting after
      incubation with a normal nonpregnancy sera pool, immunoblotting, and specific
      protease assay. In the growth study, circulating maternal IGF-I and IGFBP-3
      levels were not different in the three groups, but fetal IGF-I and IGFBP-3 levels
      were significantly lower in the UPI fetuses (IGF-I, 6.9 +/- 0.5 micrograms/L;
      IGFBP-3, 547 +/- 70 micrograms/L) than in either the nonstarved SGA fetuses (IGF
      I, 27.8 +/- 6.3; IGFBP-3, 769 +/- 41 micrograms/L; P < 0.01) or the AGA fetuses
      (IGF-I, 39.4 +/- 3.4; IGFBP-3, 872 +/- 91 micrograms/L; P < 0.01). Maternal serum
      IGFBP-3 protease activity, measured by protease using [125I]IGFBP-3 as substrate,
      was increased in pregnancies complicated by UPI compared with GA-matched
      pregnancies in which the fetus was AGA or nonstarved SGA. No significant fetal
      serum protease activity was demonstrated. In the multiple pregnancies, IGFBP-3
      rose significantly from 9-15 weeks GA in singleton (P = 0.005), twin (P = 0.004),
      and multiple (P = 0.007) pregnancies, and levels were higher in mothers of
      multiple pregnancies than in those of twin (P < 0.05) or singleton (P < 0.01)
      pregnancies at both 9 and 15 weeks GA. IGF-I levels were not different in the
      three groups and did not significantly increase between 9-15 weeks GA.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 7530259
TI  - Expression of Fc epsilon R2/CD23 and p55 IL-2R/CD25 on peripheral blood
      macrophages/monocytes in multiple sclerosis.
AB  - Macrophages have been found histologically to be activated in multiple sclerosis.
      We analyzed the expression of CD23 and CD25 on monocytes/macrophages in
      peripheral blood obtained from patients with multiple sclerosis (MS) to
      investigate their role in the demyelinating process. Peripheral blood mononuclear
      cells were obtained from 30 patients with MS including four Balo's diseases (24
      with acute relapsing type disease, six with chronic progressive type disease) and
      12 healthy controls. The percentage of CD14+CD23+ monocytes/macrophages and
      CD14+CD25+ monocytes/macrophages were determined by two-color flow cytometry. The
      percentage of CD14+CD23+ monocytes was significantly higher in patients with MS
      in the active phase as compared with controls (P < 0.01). Six patients with acute
      relapsing MS, who had received no therapy, had higher CD14+CD23+ cells than did
      controls (P < 0.0001). CD14+CD25+ monocytes/macrophages were not detected in
      peripheral blood monocytes/macrophages of patients with MS except Balo's
      concentric sclerosis. The four patients with Balo's concentric sclerosis had
      markedly elevated levels of CD14+CD25+ monocytes/macrophages. Our findings
      suggest that monocytes/macrophages are activated during an exacerbation of MS,
      and that they may play an important role in the process of demyelination.

PMID- 7530260
TI  - Local immune responses in the rat cerebral cortex after middle cerebral artery
      occlusion.
AB  - This study describes local immune responses in cerebral ischemia induced by
      permanent occlusion of the middle cerebral artery (MCAO) in the rat. The temporal
      and spatial pattern of leukocyte infiltration was characterized
      immunocytochemically using monoclonal antibodies against CD5, a pan T cell
      marker, against CD4 and CD8 for subtyping of T lymphocytes, and ED1, a marker for
      macrophages. CD5+ T cells were present in some animals on the pial surface at day
      1 and with increasing numbers mainly at the edges of the infarcts at days 3 and
      7. By day 14 their number had significantly decreased. Subtyping of T lymphocytes
      revealed that CD4+ helper/inducer T cells were rare, while CD8+ lymphocytes were
      abundant. Moreover, CD8+ lymphocytes outnumbered CD5+ T cells indicating the
      presence of CD5-/CD8+ natural killer (NK) cells. ED1+ macrophages primarily
      infiltrated the core of the infarct starting on day 1. Infiltrating leukocytes
      expressed leukocyte function associated antigen-1 and MHC class I and II
      antigens. Early after infarction, increased expression of the intercellular
      adhesion molecule-1 was found on vessels and leukocytes. In conclusion, this
      study shows that lymphocytes enter the nervous system not only in autoimmune
      diseases, but also in response to primarily 'non-immune' neuronal damage such as
      stroke.

PMID- 7530261
TI  - Study of certain clinical variables in patients with psoriasis and their relation
      to DNA content of keratinocytes.
AB  - BACKGROUND: In a previous study of 26 patients with psoriasis we analyzed
      cytophotometrically the nuclear DNA content of the germinative compartment of
      involved and uninvolved skin by means of the Feulgen technique. These subjects
      were classified into three groups according to their DNA profile. Group 1 had a
      monomodal diploid profile, group 2 showed a significantly increased 2C-4C
      population, and group 3 demonstrated high proportions of 4C and hyperdiploid
      keratinocytes. OBJECTIVE: Our purpose was to analyze clinical variables
      implicated in the development of psoriasis in reference to the three groups.
      METHODS: Nuclear DNA content of each group by quantitative histochemical studies
      was analyzed and correlated with variables such as chronologic age, sex, age at
      onset, duration of flare during the study, stress, and the Koebner phenomenon.
      RESULTS: No significant differences in DNA profile were observed in the involved
      epidermis among the clinical variables. The only differences in the uninvolved
      skin pertained to the duration of the flare, where a statistically significant
      difference was observed between groups 1 and 3 in the basal (p < or = 0.0459) and
      suprabasal keratinocytes (p < or = 0.06), and in the Koebner phenomenon, which
      was induced in all subjects (100%) in groups 2 and 3 and in only 44% of subjects
      in group 1. CONCLUSION: Uninvolved skin of patients with psoriasis should be
      included in analysis of the clinical behavior of the disease. Furthermore, the
      Koebner phenomenon is a good clinical indicator of the DNA profile of these
      subjects.

PMID- 7530262
TI  - Dermal dendrocyte hamartoma with stubby white hair: a novel connective tissue
      hamartoma of infancy.
AB  - A previously undescribed hamartoma with stubby white hair was observed in a 1
      week-old girl. A deep red, soft nodule with fine wrinkles was present on the
      back. White bizarre short thick hairs with irregular exterior cuticular squamae
      were noted. The main cells proliferating in the nodule were fibroblast-like
      spindle cells that had dendrites and showed positive staining for CD34 antigen.
      These cells surrounded vessels and nerves. In addition, there were immature hair
      follicles, relatively thick-walled small vessels, and small adipose cells with
      fine connective tissue. This hamartoma was considered to be a dermal dendritic
      cell hamartoma originating from CD34-positive cells.

PMID- 7530263
TI  - Neoplastic erythema nodosum.
AB  - We performed immunohistologic studies on a 75-year-old white woman with erythema
      nodosum (EN) and a systemic lymphoma. A skin biopsy specimen from an EN lesion
      showed lobular and septal pannicular infiltration by atypical lymphocytes. The
      cutaneous lymphocytic infiltrate was composed of a monoclonal population of B
      cells with lambda light chains. Atypical lymphocytes were also seen in the
      peripheral blood, and flow cytometry showed a predominance of the same phenotype
      of B cells with lambda light chains. Chemotherapy for systemic B-cell lymphoma
      resulted in the simultaneous resolution of EN and the lymphoma. This is the first
      documentation of EN representing direct cutaneous invasion by a B-cell lymphoma.

PMID- 7530264
TI  - Relation between heart rate variability and spontaneous and induced ventricular
      arrhythmias in patients with coronary artery disease.
AB  - OBJECTIVES: The aim of this study was to determine the relation between autonomic
      control of heart rate and the spontaneous occurrence and inducibility of
      ventricular arrhythmias in patients with coronary artery disease. BACKGROUND: Low
      heart rate variability increases the risk of arrhythmic events. It is not known
      whether impaired autonomic heart rate control reflects alterations in functional
      factors that contribute to the initiation of spontaneous arrhythmias or whether
      it is the consequence of an anatomic substrate for reentrant tachyarrhythmias.
      METHODS: Fifty-four patients with coronary artery disease with a history of
      sustained ventricular tachycardia (n = 25) or cardiac arrest (n = 29) were
      studied by 24-h ambulatory electrocardiographic recording and by programmed
      electrical stimulation. Heart rate variability was compared among the patients
      with and without spontaneous ventricular arrhythmias and with and without
      inducibility of sustained ventricular tachyarrhythmias. RESULTS: Eight patients
      had a total of 21 episodes of sustained ventricular tachycardia on Holter
      recordings. Standard deviation of RR intervals and low frequency and very low
      frequency components of heart rate variability were significantly blunted in
      patients with sustained ventricular tachycardias compared with those without
      repetitive ventricular ectopic activity (p < 0.05, p < 0.01 and p < 0.05,
      respectively). However, no significant alterations were observed in heart rate
      variability before the onset of 21 episodes of sustained ventricular tachycardia.
      Heart rate variability did not differ between the patients with or without
      nonsustained episodes of ventricular tachycardia. In patients with frequent
      ventricular ectopic activity, low frequency and very low frequency power
      components were significantly blunted compared with those with infrequent
      ventricular ectopic activity (p < 0.01 and p < 0.001, respectively). Heart rate
      variability did not differ significantly between the patients with and without
      inducible sustained ventricular tachyarrhythmias. CONCLUSIONS: Impaired very low
      and low frequency oscillation of heart rate reflects susceptibility to the
      spontaneous occurrence of ventricular arrhythmias but may not reflect the
      instantaneous triggers for life-threatening arrhythmias or a specific marker of
      the arrhythmic substrate for ventricular tachyarrhythmias.

PMID- 7530265
TI  - Antibody responses in the wild vole, Clethrionomys rufocanus bedfordiae,
      naturally infected with Echinococcus multilocularis by western blotting.
AB  - Antibody responses against crude antigens and the two (Em18 and Em16) epitopes of
      Echinococcus multilocularis were analysed by Western blotting using sera from the
      wild vole, Clethrionomys rufocanus bedfordiae (Crb), which were captured in
      Hokkaido, Japan and found to have been naturally infected with eggs, and compared
      with those in patients of AHD and mice experimentally infected with protoscoleces
      of this parasite. Antibody responses in the wild were demonstrated most clearly
      with anti-Crb-IgG antiserum but more faintly with anti-rat-IgG antiserum and
      poorly with anti-mouse-IgG or anti-human-IgG antisera or Protein G. Although only
      two serum samples of the wild vole found naturally infected were analysed,
      antibody responses against Em18 and Em16 in these voles appeared to be similar to
      those in AHD patients but differed from those in mice.

PMID- 7530266
TI  - Use of a gene-targeted phage display random epitope library to map an antigenic
      determinant on the bluetongue virus outer capsid protein VP5.
AB  - We describe the use of a gene-targeted random epitope library for the mapping of
      antigenic determinants. A DNA clone encoding the target antigen was digested
      randomly with DNase I to generate a population of DNA fragments of different
      sizes and sequences. After size fractionation, small DNA fragments (100-200 bp)
      were isolated and cloned into the phage expression vector fUSE2 to form an
      expression library displaying random polypeptide sequences as fusion proteins at
      the N terminus of the phage gene III protein. This library, termed a gene
      targeted random epitope library to distinguish it from totally random synthetic
      epitope libraries, was then screened by affinity selection for recombinant phages
      which were specifically bound by the antibody of interest. Using this approach,
      we have mapped a monoclonal antibody (mAb)-defined epitope on the bluetongue
      virus outer capsid protein VP5. This epitope is not accessible on the intact
      virus surface, but is recognised by the immune system of sheep and cattle during
      virus infection. Although the example given here utilised a DNA fragment of known
      sequence and the library was screened for a mAb-defined epitope, the strategy
      described should be equally applicable to genes of unknown sequence and for
      screening of epitopes using polyclonal antibodies. The approach can also be
      extended to identify immunodominant epitope from much more complex genome
      targeted random epitope library for virus, bacteria and eukaryotic organisms.
      Other applications of recombinant phages expressing defined immunodominant
      epitopes include serodiagnosis and vaccine development.

PMID- 7530267
TI  - A sequential binding assay with a working range extending beyond seven orders of
      magnitude.
AB  - A new immunometric sequential binding assay has been developed in which the
      sample is first reacted with a solid phase binding partner in low concentration,
      and subsequently with a second binding partner at a higher concentration. The
      amounts of analyte bound to the two solid phase binding partners are separately
      measured, thus establishing a double standard curve. There is a shift between the
      two standard curves along the concentration axis. Thus an unambiguous
      determination of analyte concentration is obtained, even in the descending region
      of the curves where the 'hook' effect causes decreasing signal with increasing
      analyte concentration. A two-particle immunofluorometric assay for AFP based on
      this principle measured by flow cytometry, resulted in an assay with rapid
      binding (approximately 2 h), a detection limit of 0.1 kIU/l and a working range
      (0.3 to > 3 x 10(6) kIU/l) in excess of 7 log10 orders. Assay results compared
      well with those of an immunoradiometric assay.

PMID- 7530268
TI  - Dual analyte assay based on particle types of different size measured by flow
      cytometry.
AB  - Simultaneous flow cytometric assays have been developed for alpha-fetoprotein
      (AFP) and human chorionic gonadotropin (hCG), with internal determination of
      sample related non-specific binding (NSB). The assays use particles of 7.5, 6.5
      and 5.5 microns diameter coated with, respectively, monoclonal antibodies
      specific for AFP, hCG or an epitope normally not present in serum. The different
      particle types were identified simultaneously by light-scatter measurements as
      their specific immunofluorometric responses were determined. The NSB in the
      simultaneous assay of AFP and hCG was increased by approximately 30% compared to
      corresponding single analyte assays. The working range of the dual analyte assays
      was 0.6-2000 kIU/l for AFP and 6-10,000 IU/l for hCG. No significant interference
      from the presence of the other analyte was observed in the measurement of either
      AFP or hCG. The 95% confidence interval for the ratio of dual over single analyte
      assay results was [0.81, 1.11] for AFP and [0.88, 1.16] for hCG.

PMID- 7530270
TI  - Expression of transglutaminase 1 in human epidermis.
AB  - To explore the expression and function of the membrane-associated or type I
      transglutaminase (TGase1) in human epidermis, we have made a new antihuman TGase1
      antibody in goats elicited against a purified active recombinant protein
      expressed in bacteria. By use of Western blotting and immunoprecipitation
      methods, the antibody reacted with high specificity with only the TGase1 activity
      of the epidermis and in cultured keratinocytes. By indirect immunofluorescence,
      the antibody decorated the entire epidermis, including the basal layer, with some
      potentiation of the granular layer. However, these staining properties are quite
      different from those of a widely used, commercially available TGase1 monoclonal
      antibody (termed B.C1), which decorates the granular layers of the epidermis. By
      Western blotting, it identifies the TGase1 protein band only weakly, but
      recognizes strongly a group of bands of 15-20 kDa, two of which by amino acid
      analysis and amino acid sequencing are the small proline-rich (SPR) 1 and SPR2
      proteins, also expressed in epidermal and epithelial tissues. Together with a
      series of blocking experiments with TGase1 proteins and synthetic peptides, these
      data reveal that the major epitope of the B.C1 antibody most likely resides on
      the amino-terminus of these two SPR proteins rather than on TGase1. Further
      studies will now be necessary to determine the role(s) of TGase1 during the
      different stages of development and differentiation in the epidermis.

PMID- 7530269
TI  - Co-administration of insulin-like growth factor (IGF)-I and IGF-binding protein-1
      stimulates wound healing in animal models.
AB  - The stimulatory effect of recombinant human insulin-like growth factor-I (rhIGF
      I) and recombinant human insulin-like growth-factor-binding protein-1 (rhIGFBP-1)
      on wound healing was assessed using diabetic db/db mice and normal rabbits. Full
      thickness wounds of 6 mm diameter were prepared on the backs of diabetic
      C57BL/KsJ db/db mice and on the inner sides of normal rabbit ears. Various
      concentrations of rhIGF-I and/or rhIGFBP-1 were applied locally to the open
      wounds of db/db mice once daily for 5 d and to the covered wounds of normal
      rabbits once after wounding. Sections of the wounds were evaluated histologically
      on the seventh or eighth day by measuring re-epithelialization (%), area of
      granulation tissue (mm2), and capillary numbers. Wound repair was accelerated by
      each of the treatments in descending order of rhIGF-I plus rhIGFBP-1, rhIGF-I,
      rhIGFBP-1, and vehicle alone. In db/db mice, the combination of 50 micrograms
      rhIGF-I and 165 micrograms rhIGFBP-1 (equimolar ratio) significantly stimulated
      granulation tissue formation (p < 0.01) and capillary numbers (p < 0.05). Doses
      of rhIGFBP-1 greater than 16.5 micrograms were required for significant
      acceleration of the healing stimulated by 50 micrograms of rhIGF-I. In normal
      rabbits, co-administration of 10 micrograms rhIGF-I and 33 micrograms rhIGFBP-1
      (equimolar ratio) significantly stimulated all three wound-healing parameters (p
      < 0.01), with such stimulation being much greater than that induced by rhIGF-I
      alone. Interestingly, rhIGFBP-1 alone showed a mild stimulatory activity on wound
      healing in both models despite its lack of mitogenic activity in vitro. These
      results demonstrate that rhIGFBP-1 enhances the stimulatory activity of rhIGF-I
      on wound healing and suggest the clinical utility of the co-administration of
      rhIGF-I and rhIGFBP-1 for wound repair.

PMID- 7530271
TI  - Immunodominant autoepitopes of type VII collagen are short, paired peptide
      sequences within the fibronectin type III homology region of the noncollagenous
      (NC1) domain.
AB  - Autoantibodies to type VII collagen are associated with the blistering diseases
      epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. We
      showed previously that these autoantibodies recognize epitopes within the
      noncollagenous (NC1) region of type VII collagen. That region is composed of
      fibronectin type III homology units that may contribute to intermolecular cross
      linking and basement membrane adhesion functions of type VII collagen. In this
      study, we defined the specific amino acid sequences recognized by these
      autoantibodies. By fusion protein analysis, sera from patients with epidermolysis
      bullosa acquisita and bullous lupus were found to react with two regions within
      the fourth (E-1) and eighth (E-2) fibronectin homology repeats, each consisting
      of approximately 100 amino acids. Affinity purification studies showed E-1 and E
      2 to be independent and non-cross-reactive epitope regions. These regions were
      probed further by enzyme-linked immunosorbent assay analysis of overlapping
      octapeptide sets derived from the amino acid sequences of E-1 and E-2. The
      results showed two reactive, closely associated octapeptide sequences within each
      region, both lying in amphipathic portions of fibronectin type III homology
      repeats. These studies identify short peptide sequences within the NC1 domain of
      type VII collagen that are targeted independently by autoantibodies. These
      sequences may play a direct role in determining the properties of type VII
      collagen that influence adhesion between this molecule and other basement
      membrane proteins, and their alteration by antibody binding may be the
      immunopathogenic event underlying epidermolysis bullosa acquisita and bullous
      lupus.

PMID- 7530272
TI  - Melanocyte mitogens induce both melanocyte chemokinesis and chemotaxis.
AB  - It is believed that during repigmentation of vitiligo, inactive melanocytes in
      the outer root sheath of the hair follicle become activated, proliferate, and
      migrate into the depigmented skin. However, the mechanisms controlling melanocyte
      migration remain to be elucidated. In this study, we investigated the effects of
      well-described melanocyte growth factors on melanocyte migration. Using time
      lapse photography, we demonstrated that melanocyte chemokinetic movement was
      induced by basic fibroblast growth factor, stem cell factor, and endothelin-1,
      with the greatest effect noted using 100 nM endothelin-1. Similar results were
      reported previously with leukotriene C4. When surrounded by these stimuli,
      melanocytes moved in a random, nonlinear fashion and showed no desensitization at
      the concentrations studied. In Boyden chamber checkerboard analysis, basic
      fibroblast growth factor, leukotriene C4 and endothelin-1 were chemotactic. They
      produced directional migration and showed desensitization at higher
      concentrations. The greatest effect again was seen with 100 nM endothelin-1. Stem
      cell factor showed no effect in this assay system at the concentrations tested.
      The four melanocyte mitogens--leukotriene C4, endothelin-1, basic fibroblast
      growth factor, and stem cell factor--stimulate melanocyte migration, and this
      migration may be either chemokinetic (activated random movement) or chemotactic
      (requiring a gradient, directional, and showing desensitization), depending on
      the conditions used. We believe that these factors may be effective in
      stimulating vitiligo repigmentation by inducing proliferation and migration of
      hair-follicle outer-root-sheath melanocytes into the depigmented epidermis.

PMID- 7530273
TI  - Cell density and culture factors regulate keratinocyte commitment to
      differentiation and expression of suprabasal K1/K10 keratins.
AB  - Irreversible growth arrest and commitment to differentiation are among the
      earliest events in the program of cellular terminal differentiation. The
      transition from highly proliferative human keratinocytes in subconfluent culture
      to stationary cells in confluent culture was studied in a serum-free culture
      system to identify conditions that regulate the initiation of terminal
      differentiation in keratinocytes. We observed that culture confluence strongly
      induced commitment to terminal differentiation, as demonstrated by a dramatic
      loss of keratinocyte clonogenicity. Commitment was accompanied by the rapid
      induction of early differentiation markers, represented by expression of
      suprabasal keratin 1 (K1) and 10 (K10) genes. Induction of differentiation was
      independent of low (0.1 mM) or high (1.5 mM) calcium concentration in the medium.
      Epidermal growth factor suppressed expression of K1 and K10 mRNA in cultures
      induced to differentiate. Suspension of keratinocytes in methylcellulose medium
      failed to induce in subconfluent cultures, or enhance in confluent cultures, the
      expression of K1 and K10 genes. Subconfluent cells cultured in medium containing
      high calcium and no exogenous growth factor induced expression of K1 and K10
      transcripts, but commitment and loss of proliferative potential were not
      observed. Confluent cell density primarily controlled keratinocyte commitment to
      terminal differentiation and differentiated keratin gene expression. However,
      suprabasal K1 and K10 gene expression also was regulated by medium calcium and
      exogenous growth-factor concentrations in subconfluent cultures that promoted
      cell-cell association. Epidermal growth factor inhibited the expression of
      suprabasal keratins but not the commitment to terminal differentiation mediated
      by cell confluence. Control of keratinocyte commitment and expression of selected
      differentiation genes are mediated by cell confluence and, at subconfluence, by
      specific culture factors.

PMID- 7530274
TI  - Pentoxifylline, pentifylline, and interferons decrease type I and III procollagen
      mRNA levels in dermal fibroblasts: evidence for mediation by nuclear factor 1
      down-regulation.
AB  - Pentoxifylline (PTX) is a methylxanthine that exhibits multiple biologic
      activities, including the inhibition of collagen synthesis by dermal fibroblasts.
      Because some PTX activities have recently been linked to transcription factor
      mediated regulation of gene transcription, we have investigated if PTX acts to
      inhibit collagen synthesis at a transcriptional locus by measuring procollagen
      mRNA levels by assaying for the presence of an activator of procollagen gene
      promoters, nuclear factor (NF)-1. The effects of another methylxanthine,
      pentifylline (PTF), shown herein to be a tenfold more potent inhibitor of
      collagen synthesis than PTX, and interferon-alpha, -beta, and -gamma were studied
      in parallel. Analysis of extracellular protein and RNA from 48-h-treated
      fibroblasts showed that PTX, PTF, and interferons decreased alpha 1(I), alpha
      2(I), and alpha 1(III) procollagens by reducing the steady-state levels of the
      corresponding procollagen mRNA transcripts. Reduction of procollagen mRNA levels
      appeared to be dependent on new protein synthesis, as it was prevented by
      treatment with cycloheximide. Assay for the presence of nuclear NF-1 by gel
      mobility shift analysis showed that extracts from interferon, PTX, and PTF
      treated fibroblasts lacked proteins recognizing the consensus DNA binding
      sequence for NF-1. Taken together, these observations suggest interferons and
      methylxanthines may inhibit fibroblast collagen synthesis by a common mechanism
      requiring new protein synthesis that suppresses procollagen gene transcription
      through down-regulation of NF-1.

PMID- 7530275
TI  - Behavior of bone alkaline phosphatase (BAP) determined with immunoradiometric
      assay in metastatic prostate cancer.

PMID- 7530276
TI  - Neuropeptide-mediated regulation of hapten-specific IgE responses in mice. I.
      Substance P-mediated isotype-specific suppression of BPO-specific IgE antibody
      forming cell responses induced in vivo and in vitro.
AB  - The ability of substance P (SP) to regulate peak benzyl-penicilloyl (BPO)
      specific IgE antibody-forming cell (AFC) responses in vivo and the ability of SP
      and other neuropeptides to regulate BPO-specific memory IgE AFC responses induced
      in vitro was determined. SP injected subcutaneously into BPO-keyhole limpet
      hemocyanin (BPO-KLH)-sensitized mice at the time of peak IgE responses suppressed
      these responses within 48 h (> 90%). The suppression obtained was IgE isotype
      specific, dose-dependent, and transient. When spleen cells from immunized mice
      were cultured for 5 days with BPO-KLH, peak memory IgE AFC responses were induced
      in vitro. Inclusion of either SP or vasoactive intestinal peptide (VIP), but not
      neurotensin, serotonin, somatostatin, or gastrin, in cultures suppressed these
      responses in isotype-specific, dose-dependent fashion (approximately 70%). SP-,
      but not VIP-mediated suppression of IgE responses was abrogated by inclusion of
      anti-IFN gamma culture.

PMID- 7530277
TI  - Lymphocyte-mediated nitric oxide production by rat endothelial cells.
AB  - Lymphocyte migration from the blood to sites of tissue injury is mediated, in
      part, through the interaction of these cells with endothelial cells lining the
      vessel walls. The ability of endothelial cells to produce nitric oxide may be
      important in this process. We found that the addition of the nonspecific
      lymphocyte activators lipopolysaccharide (LPS) or concanavalin A (Con A) to rat
      hepatic endothelial cell cultures from control or endotoxemic rats markedly
      enhanced the ability of these cells to produce nitric oxide. In contrast, wheat
      germ agglutinin (WGA) and phytohemagglutinin (PHA) had no effect on nitric oxide
      release. Coculture of endothelial cells with lymphocyte-rich preparations of rat
      thymocytes or splenocytes stimulated endothelial cell nitric oxide production.
      This response was enhanced by LPS or Con A and to a lesser extent by WGA or PHA.
      In contrast to endothelial cells, thymocytes and splenocytes did not produce
      nitric oxide either in the presence or absence of lymphocyte mitogens. Increased
      production of nitric oxide by endothelial cells in response to lymphocytes and
      lymphocyte mitogens was due, at least in part, to increased expression of protein
      for an inducible form of nitric oxide synthase, as measured by Western blotting.
      Stimulation of endothelial cell nitric oxide production by thymocytes and
      splenocytes was inhibitable by the specific nitric oxide synthase inhibitor NG
      monomethyl-L-arginine and dependent on cell-cell contact. Thus, nitric oxide
      production by endothelial cells was reduced when the lymphocytes were physically
      separated from the endothelial cells using cell culture inserts. We hypothesize
      that nitric oxide released by endothelial cells increases vascular permeability,
      thereby allowing the extravasation of lymphocytes into the surrounding tissue, a
      process that may be important in inflammation, tissue injury, and/or wound
      healing.

PMID- 7530278
TI  - Characterization of nitric oxide-stimulated ADP-ribosylation of various proteins
      from the mouse macrophage cell line ANA-1 using sodium nitroprusside and the
      novel nitric oxide-donating compound diethylamine dinitric oxide.
AB  - We examined the ability of nitric oxide (NO) to stimulate the ADP-ribosylation of
      proteins from the mouse macrophage cell line ANA-1. To demonstrate a specific
      effect of NO, we used a novel compound named diethylamine dinitric oxide (DEA/NO;
      1,1-diethyl-2-hydroxy-2-nitrosohydrazine, sodium salt; [Et2NN(O)NO]Na), which
      releases NO in aqueous solution at neutral pH. DEA/NO stimulated the ADP
      ribosylation of at least three cytosolic proteins (M(r) = 28,000, 33,000 and
      39,000) from ANA-1 macrophages. The effect of DEA/NO on the ADP-ribosylation of
      the predominant target p39 was dose dependent (EC50 = 80 microM). Moreover, the
      effect of DEA/NO was attributed specifically to released NO rather than
      diethylamine or nitrite. Sodium nitroprusside (SNP) also stimulated the ADP
      ribosylation of cytosolic proteins from ANA-1 mouse macrophages. However, SNP
      exhibited different time- and dose-dependent effects on the modification of p39.
      NO synthesized via the activity of interferon-gamma plus lipopolysaccharide
      induced NO synthase also enhanced the ADP-ribosylation of p39, confirming that
      the effects of DEA/NO and SNP could be attributed to NO or reactive nitrogen
      oxide species. Neither pertussis toxin nor cholera toxin stimulated the ADP
      ribosylation of p39; however, cholera toxin stimulated the ADP-ribosylation of
      proteins with approximate molecular weight of 28,000 and 33,000. These data
      suggest that the induced expression of NO synthase in tumoricidal macrophages may
      be associated with autocrine and paracrine effects of NO that include the ADP
      ribosylation of various proteins. Moreover, these results indicate that DEA/NO
      and related compounds may be useful as pharmacologic tools for investigating the
      effects of NO and reactive nitrogen oxide species on macrophages.

PMID- 7530279
TI  - Expression of glycophosphatidylinositol-anchored and -non-anchored isoforms of
      vascular cell adhesion molecule 1 in murine stromal and endothelial cells.
AB  - Monoclonal antibodies to murine vascular cell adhesion molecule-1 (VCAM-1, CD106)
      revealed not only the expected VCAM-1 molecule with an apparent molecular weight
      of 100 kDa, but also a molecule with a smaller size of 46 kDa in stromal cells
      and stimulated endothelial cells. Peptide mapping suggested the 46 kDa and 100
      kDa proteins were closely related. The 46 kDa, but not 100 kDa protein, was
      cleaved from the cell surface with phosphatidylinositol-specific phospholipase C
      (PI-PLC), showing that the 46 kDa protein was a GPI-linked molecule. The 46 kDa
      and 100 kDa isoforms of VCAM-1 were shown to be N-glycosylated, have similar
      kinetics of biosynthesis, and to be partially shed from the cell surface with a
      slight reduction of size. TNF-alpha induced both isoforms of VCAM-1 with a
      similar time course of appearance on the surface of endothelial cells. The
      relative amounts of the 46 kDa and 100 kDa isoforms depended on the cell type
      examined. The GPI-anchored isoform is functionally important, because on a cell
      on which it was expressed almost as well as the 100 kDa isoform, treatment with
      PI-PLC reduced VLA-4-dependent conjugate formation.

PMID- 7530281
TI  - Cellular localization and hormonal regulation of inducible nitric oxide synthase
      in cycling mouse uterus.
AB  - Nitric oxide (NO), a potent and versatile free radical, is synthesized in
      macrophages and mast cells as well as in other types of cells by the inducible
      form of nitric oxide synthase (iNOS). In this study, cells containing iNOS were
      identified in the uteri of cycling mice by using a rabbit antibody generated to
      an iNOS-specific peptide. Macrophages were identified in semiserial sections of
      the same tissues with the monoclonal antibody, F4/80, and mast cells were
      identified by toluidine blue staining. In tissue sections of uteri obtained from
      mice in the four stages of the estrous cycle (8 to 11 mice per stage), iNOS
      immunoreactivity was strongest in diestrus-I uteri and weakest in diestrus-II
      uteri. Myometrial mast cells and endometrial epithelial cells were prominent
      locations of iNOS, and specific protein was also present in myometrial smooth
      muscle and macrophage-like cells in the endometrial stroma. Because cyclic
      variations suggested regulation of iNOS expression by ovarian steroid hormones,
      studies were done using ovariectomized mice. Seven days after ovariectomy,
      immunoreactive iNOS was low but detectable in mast cells and luminal epithelial
      cells. In the uteri of ovariectomized, estradiol-17 beta (E2)-treated mice, mast
      cells were iNOS+ after 24 h whereas epithelial cells were negative; the reverse
      was observed in progesterone (P4)-treated mice. Both mast cells and epithelial
      cells were iNOS+ in the uteri of mice that had received a combination of E2 + P4.
      These results indicate that several types of uterine cells produce iNOS and that
      expression of this enzyme in specific cell lineages is governed by ovarian
      steroid hormones. The data are consistent with the postulate that NO derived from
      uterine leukocytes and other types of cells plays a role in uterine cyclicity and
      preparation for pregnancy.

PMID- 7530282
TI  - Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in
      reversible endotoxic shock studied by a novel monoclonal antibody against rat
      iNOS.
AB  - An antirat monoclonal antibody (mAb) against inducible nitric oxide synthase
      (iNOS), ANOS11, was used for immunohistochemistry to examine the expression of
      iNOS in various organs and tissues of adult rats in experimental endotoxic shock
      induced by lipopolysaccharide (LPS) injection. The phenotype of iNOS-expressed
      cells was also examined immunohistochemically using various mAbs. In control
      rats, very few cells were positive for ANOS11 except in the thymus. After
      intravenous injection of LPS, the number of iNOS-positive cells increased rapidly
      in almost all organs, except the thymus and brain, peaked 6 h after the
      injection, and decreased slowly. Of the numerous inflammatory cells that
      infiltrated the lungs, liver, and spleen after LPS injection, many were positive
      for ANOS11. Besides inflammatory cells, hepatocytes and endothelial cells of the
      aorta were also positive for ANOS11 but only around 6 h after injection. The
      cellular composition of iNOS-positive infiltrated cells changed along with the
      progression of endotoxic shock. At 4 to 6 h after injection, most iNOS-positive
      cells were considered polymorphonuclear leukocytes judging by their positive
      reactivity to OX42 and their nuclear morphology. The population of iNOS-positive
      macrophages positive for ED1 or ED2 increased with time. After 24 h, many iNOS
      positive macrophages were found around the focal necrosis in the liver and
      spleen. These results indicate that the expression of iNOS in neutrophils,
      endothelial cells, and hepatocytes precedes that of macrophages in experimental
      endotoxic shock. The expression of iNOS in various cells and organs is closely
      associated with the progress and pathological changes of endotoxic shock.

PMID- 7530280
TI  - Modification of leukocyte adhesion in spontaneously hypertensive rats by adrenal
      corticosteroids.
AB  - Leukocyte adhesion is a key factor in the pathogenesis of organ injury following
      a variety of stimuli. In this study we have addressed the role of leukocyte
      adhesion in hypertensives as a risk factor for organ injury. In the spontaneously
      hypertensive rat (SHR), the number of circulating leukocytes and their level of
      activation are significantly increased compared with its normotensive control,
      the Wistar-Kyoto rat (WKY). We have demonstrated that elevated levels of
      glucocorticoid in SHR suppress P-selectin-mediated leukocyte-endothelial
      interaction in the microcirculation. It is possible that the disturbance in
      leukocyte-endothelial interactions may result in an elevated number of leukocytes
      in the circulation. The aim of the present study was to investigate the
      contribution of the adrenal glands to the disturbance in leukocyte behavior in
      SHR by subjecting the animals to bilateral adrenalectomy and investigating the
      effect of hydrocortisone. In addition, we have studied by immunohistochemistry
      the expression of the endothelial adhesion molecule, P-selectin, in response to
      histamine in the mesenteric venules of normal and adrenalectomized SHR and WKY.
      The elevated blood pressure, above-normal leukocyte counts, and elevated number
      of activated neutrophils (nitroblue tetrazolium test) in SHR were blunted after
      adrenalectomy. The blunted histamine-induced leukocyte-endothelial interaction in
      the mesenteric venules of SHR was restored after adrenalectomy. Treatment with
      hydrocortisone significantly attenuated the elevated leukocyte adhesion in the
      adrenalectomized SHR as well as in WKY. The suppressed P-selectin expression in
      SHR mesentery was restored after adrenalectomy. In conclusion, the subnormal
      leukocyte-endothelial interaction in response to an inflammatory stimulation in
      SHR is abolished after adrenalectomy, suggesting a relationship between the
      altered leukocyte adhesiveness and the adrenal corticosteroids in hypertensives.

PMID- 7530283
TI  - Time course of coronary vascular endothelial adhesion molecule expression during
      reperfusion of the ischemic feline myocardium.
AB  - The time course of endothelial P-selectin, ICAM-1, and E-selectin expression was
      studied in a feline model of myocardial ischemia and reperfusion. Cats were
      subjected to 90 min of myocardial ischemia followed by 0, 10, 20, 60, 150, or 270
      min of reperfusion. At the end of reperfusion, the coronary vasculature was
      examined immunohistochemically to localize monoclonal antibodies (mAbs) PB1.3,
      RR1/1, and Cy1787 directed against P-selectin, ICAM-1, and E-selectin,
      respectively. Immunohistochemical localization for P-selectin, recognized by mAb
      PB1.3, was maximally expressed 20 min after reperfusion in 60 +/- 6% of coronary
      venules (P < 0.05 compared to non-reperfused controls), and covered 59 +/- 3% of
      the endothelial cell perimeter of immunostained coronary venules.
      Immunolocalization of mAb PB1.3 gradually declined at 60, 150, and 270 min of
      reperfusion. Immunohistochemical localization of mAb RR1/1 (anti-ICAM-1) in
      endothelial cells of coronary venules was observed to a modest extent in non
      ischemic myocardium and at 10, 20, and 60 min of reperfusion, but was
      significantly increased following 150 and 270 min of reperfusion (P < 0.05
      compared non-reperfused controls). At 270 min post-reperfusion, mAb RR1/1 was
      seen in 50 +/- 4% of coronary venules. Endothelial immunolocalization of mAb
      Cy1787 (anti-E-selectin) was only observed in 13 +/- 1 and 14 +/- 3% of coronary
      venules after 150 and 270 min of reperfusion, respectively, suggesting that
      pronounced expression of E-selectin does not occur within 270 min after
      reperfusion. These results demonstrate sequential expression of three major
      endothelial cell adherence molecules in situ following myocardial ischemia and
      reperfusion. The timing of endothelial cell expressed P-selectin and ICAM-1 could
      coordinate neutrophil trafficking during the early stages of reperfusion.

PMID- 7530284
TI  - Distinct granzyme expression in human CD3- CD56+ large granular- and CD3- CD56+
      small high density-lymphocytes displaying non-MHC-restricted cytolytic activity.
AB  - Cultured natural killer (NK) cells derived from CD3- CD56+ high-density small
      lymphocytes (HDLs) exhibit similar morphology and high levels of non-major
      histocompatibility complex-restricted (NK) cytotoxicity equivalent to those of
      cultured NK cells from CD3- CD56+ low-density large granular lymphocytes (LGLs).
      To examine the similarities and differences between NK cells from HDLs and NK
      cells from LGLs, we investigated the expression of three distinct members of the
      granule serine protease (granzyme) family within cultured CD3- CD56+ LGLs and
      HDLs. CD3- subpopulations of nonadherent peripheral blood mononuclear cells, LGLs
      (density < 1.063 g/ml), and HDLs (density > 1.063 g/ml) were stimulated to
      proliferate in culture. The cultured cells from each population were entirely CD3
      CD56+ and were indistinguishable in terms of their increased granularity and
      size once activated. All cultured CD3- CD56+ LGLs and HDLs displayed cytolytic
      activity against K562 and immunoglobulin-coated P815. Western analysis detected
      perforin in both cultured LGL and HDL populations. Cultured HDLs and LGLs both
      expressed BLT-esterase activity and human granzyme A mRNA. Granzyme B mRNA and
      protein and Asp-ase activity were detected in unstimulated and cultured LGLs and
      cultured HDLs. By contrast, unstimulated HDLs did not express significant levels
      of granzyme B. High levels of Hu-Met-1 granzyme mRNA and Met-ase activity were
      detected only in cultured LGLs. Thus, despite the development of large granular
      morphology during proliferation, interleukin-2 cultured CD3- CD56+ HDLs display a
      different pattern of granzyme expression from CD3- CD56+ LGLs. These data also
      further suggest an unusually restricted expression of the Hu-Met-1 granzyme in
      LGLs.

PMID- 7530285
TI  - Differential regulation of insulin-like growth factor binding protein-2 and -4
      mRNA in muscle tissues and liver by diabetes or fasting.
AB  - The present study was undertaken to investigate the metabolic regulation of
      insulin-like growth factor binding proteins (IGFBPs) gene expression in muscles
      from diabetic or fasted rat. The messenger RNA (mRNA) levels for IGFBP-2 and -4
      were analysed by solution hybridization in heart, skeletal and smooth muscle and
      liver from fasted (3 days) and refed (6, 12, 24, 72 h) rats and rats made
      diabetic with streptozotocin. In aortic intima-media, the mRNA levels for IGFBP-2
      and -4 were decreased by diabetes or fasting and were restored gradually by
      refeeding. The response of IGFBP-4 mRNA to diabetes appeared two days after
      injection of streptozotocin, while a significant decrease of IGFBP-2 mRNA was
      found after a diabetes duration of two weeks. Both diabetes and fasting decreased
      IGFBP-4 mRNA levels in heart muscle and skeletal muscle and refeeding restored
      mRNA for IGFBP-4 to normal level. IGFBP-2 mRNA was undetectable in heart muscle
      and skeletal muscle. In liver IGFBP-4 mRNA was abundantly expressed. It was
      slightly but significantly decreased by fasting and approached normality with
      refeeding, while no change was found in diabetic liver. In contrast, liver IGFBP
      2 mRNA was much lower in amount than IGF-I mRNA and IGFBP-4 mRNA and was sharply
      elevated by fasting, and decreased by refeeding. In conclusion, 1) both IGFBP-2
      and -4 mRNA in various tissues are regulated by diabetes or fasting; 2) the mRNA
      for IGFBP-2 is metabolically regulated in a discordant, organ-specific manner.

PMID- 7530286
TI  - Androgen and oestrogen responsiveness of stromal cells derived from the human
      hyperplastic prostate: oestrogen regulation of the androgen receptor.
AB  - Stromal cells derived from collagenase-digested benign hyperplastic adult
      prostates were isolated and grown in culture. Androgen and oestrogen receptor
      status were determined and growth in response to mibolerone (a synthetic
      androgen) and oestradiol-17 beta was measured. In addition, the ability of
      oestrogens to regulate the androgen receptor in stromal cells was investigated.
      [3H]Thymidine incorporation into DNA was stimulated by mibolerone in primary and
      secondary cultures, but sensitivity was lost with subsequent passages. Androgen
      stimulation of [3H]thymidine incorporation was consistently inhibited by the anti
      androgen cyproterone acetate. Oestradiol-17 beta also stimulated [3H]thymidine
      incorporation into DNA, and this effect was inhibited by the anti-oestrogen
      tamoxifen. Sensitivity to oestradiol was lost with subsequent passages. A
      combination of mibolerone and oestradiol was not synergistic in increasing
      [3H]thymidine incorporation into DNA, but maximal stimulation occurred at 100
      fold lower concentrations of mibolerone and oestradiol when the two hormones were
      applied in combination. Specific high-affinity [3H]mibolerone- and [3H]oestradiol
      binding sites were demonstrated by radioligand binding in intact cells. The
      affinity for oestradiol binding to its receptor exceeded that quantified for
      mibolerone binding to the androgen receptor, whilst the number of oestradiol
      binding sites was approximately tenfold less than that quantified for mibolerone.
      Treatment with oestradiol down-regulated the number of [3H]mibolerone binding
      sites 1.7-fold (P < 0.005) as early as day 2 after oestradiol treatment. In
      conclusion, we successfully cultured stromal cells derived from hyperplastic
      prostates which retained sensitivity to androgen and oestrogen.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7530288
TI  - Isolation and characterization of distinct bioactive forms of LH from male
      buffalo pituitaries: differences localized to their alpha subunits.
AB  - The isolation of highly purified forms of pituitary LH from Egyptian male (Nile)
      buffaloes is described. The total LH content (receptor binding activity) which
      was approximately 30 to 50 fold higher than FSH in the pituitary could be divided
      into three pools based upon fractionation patterns on a cation exchanger. The
      acidic fraction which also contained FSH was not purified to homogeneity. A basic
      fraction (bu-LH-2; 300 mg/kg anterior pituitary) and a very basic fraction (bu-LH
      3; 80 mg/kg) were both highly purified and free of FSH activity as tested by
      specific FSH receptor and immunoassays. The basic buffalo LH fraction, bu-LH-2,
      was as active as highly purified ovine LH (oLH). The most basic form of buffalo
      LH, bu-LH-3, was, however, about twice as active as highly purified oLH in the in
      vitro bioassay using mouse Leydig tumour (MA-10) cells. In a receptor binding
      assay employing 125I-labelled buffalo LH (bu-LH-3) and porcine testicular
      membranes, the affinity of bu-LH-3 was about five times higher than purified oLH.
      The M(r) of both forms of purified buffalo LH and subunits was similar to that of
      oLH. Amino acid composition of buffalo LH was also very similar to oLH except for
      small differences. Fractionation by fast protein liquid chromatography on Mono-Q
      columns revealed further evidence of microheterogeneity in each of the pools of
      buffalo LH with bu-LH-3 exhibiting a predominant single component. By reverse
      phase high-pressure liquid chromatography analysis we have localized differences
      in the two purified isoforms of male buffalo LH to the alpha subunit. It is
      suggested that differences in biological potencies could be due to variations in
      terminal glycosylation and/or differences in branching of this subunit which is
      known to be important for signal transduction.

PMID- 7530287
TI  - Involvement of epidermal growth factor (EGF)/EGF receptor autocrine and paracrine
      mechanism in human trophoblast cells: functional differentiation in vitro.
AB  - We have studied the expression of epidermal growth factor (EGF) and EGF receptors
      (EGF-R) in isolated human trophoblast cells at various stages of differentiation
      and also the biological significance of the EGF/EGF-R autocrine and paracrine
      mechanism. Cytotrophoblast cells were isolated from human placental tissues of 6
      9 weeks of gestation. Trophoblast cells underwent morphological and functional
      differentiation during in vitro culture. The expression of EGF and EGF-R protein
      and mRNA was studied in trophoblast cells cultured for 0-5 days, using
      immunocytochemical staining, and reverse transcription and polymerase chain
      reaction. Monoclonal antibodies (mAbs) against EGF and EGF-R showed specific
      staining in trophoblast cells at all stages of differentiation. Both EGF and EGF
      R gene transcripts were detected in RNA samples isolated from trophoblast cells
      at all stages. These data suggest the presence of an EGF/EGF-R autocrine and
      paracrine mechanism in human trophoblast cells. Next, we examined the biological
      significance of this mechanism on trophoblast cell differentiation in vitro. EGF
      added to the culture medium significantly increased human chorionic gonadotrophin
      beta (hCG-beta) secretion and, more importantly, anti-EGF neutralizing mAbs
      significantly reduced both hCG-beta and human placental lactogen secretion from
      trophoblast cells in culture. All these results suggest that human trophoblast
      cells express both EGF and EGF-R, and that EGF may play an important role in the
      functional differentiation of human trophoblast cells.

PMID- 7530290
TI  - Differential response of neuropeptide Y, substance P and vasoactive intestinal
      polypeptide in the rat anterior pituitary gland to alterations in thyroid hormone
      status.
AB  - We have compared the effects of thyroidectomy with those of thyroxine (T4)
      replacement and excess T4 treatment on neuropeptide Y (NPY) in the rat anterior
      pituitary, and compared these with the effects on substance P (SP) and vasoactive
      intestinal peptide (VIP). Thyroidectomy produced large increases in the peptide
      content of NPY (335 +/- 58 fmol/gland vs 15 +/- 4 fmol/gland in controls), SP
      (581 +/- 90 vs 199 +/- 32 fmol/gland) and VIP (1386 +/- 395 vs 417 +/- 77
      fmol/gland) together with large increases in the respective prohormone encoding
      mRNAs, NPY 21,760% +/- 1290%, preprotachykinin-A (PPT-A; which encodes the
      substance P precursor) 1744% +/- 190% and VIP 680% +/- 129%. Thyroidectomy
      together with T4 replacement produced an increase in both NPY peptide (426 +/- 72
      vs 15 +/- 4 fmol/gland) and mRNA content (970% +/- 156% of controls). The peptide
      contents of SP and VIP were not significantly different from controls. PPT-A and
      VIP mRNA levels were decreased relative to controls (31% +/- 8% and 23% +/- 10%
      respectively). In intact animals treated with excess T4 (hyperthyroid animals),
      SP and VIP peptide contents were significantly reduced (55 +/- 13 vs 199 +/- 32
      fmol/gland and 226 +/- 24 vs 417 +/- 77 fmol/gland respectively) and the SP and
      VIP encoding mRNAs were also decreased (8% +/- 3% and 11% +/- 4% respectively).
      In this group there was no detectable alteration in either the peptide or mRNA
      content of NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530291
TI  - Regional variations in the pharmacology of NMDA receptor channel blockers:
      implications for therapeutic potential.
AB  - Quantitative receptor autoradiography was used to examine the regional binding
      characteristics of a diverse group of N-methyl-D-aspartate (NMDA)-receptor
      channel blockers that varied in potency 10(5)-fold. Full competition curves were
      generated in each of six brain regions for 11 different compounds. MK-801 was the
      most potent compound studied, with an IC50 of approximately 10 nM in the
      forebrain regions and 24 nM in the cerebellar granule cell layer (p < 0.05). The
      binding affinities of nine of the 11 compounds examined were significantly
      different in cerebellar granule cell layer than in forebrain regions. In
      addition, the apparent Hill slopes of five of the compounds were significantly
      different in cerebellum compared with forebrain. That the rank order of drug
      potencies in cerebellar diverges from that in forebrain suggests that cerebellar
      NMDA-receptor ion channels differ pharmacologically from those in forebrain.
      There was a general trend that drugs known to be well tolerated in humans
      (remacemide hydrochloride and its metabolites, amantadine, budipine, and
      memantine) had lower affinities than compounds with severe neurobehavioral or
      psychotomimetic effects. Moreover, all of the compounds known to be well
      tolerated in humans had a significantly higher affinity in the cerebellum than in
      forebrain regions, in contrast to MK-801, 1-[1-(2-thienyl)cyclohexyl]-piperidine
      hydrochloride (TCP), phencyclidine (PCP), and ketamine, which had lower
      affinities in cerebellum. Our results are consistent with the notion that low
      affinity (rapid kinetics) and, possibly, subunit specificity (as indicated by
      distinct regional pharmacologies) may be important determinants of the clinical
      tolerability of NMDA-receptor channel blockers.

PMID- 7530289
TI  - The effect of epitestosterone on gonadotrophin synthesis and secretion.
AB  - The effects of 3-week treatment with increasing doses of epitestosterone (ET) on
      gonadotrophin gene expression and secretion, on testosterone and 5 alpha
      dihydrotestosterone (DHT) levels, and on the weight of testes and prostates, were
      studied in intact adult male rats. The hormones were delivered by means of
      silastic capsules of different lengths filled with the steroid. One group of rats
      received testosterone (T) instead of ET, to compare the results with previous
      studies concerning the testosterone effect. The controls were given capsules with
      glucose only. Treatment with ET, as well as with T, significantly reduced the
      weights of prostates. When the data from ET-treated rats and controls were
      combined, a significant negative correlation (P < 0.001) was found between the
      weight of prostates and serum ET. T, in contrast to ET, also decreased
      significantly the weights of testes, ET treatment caused a significant reduction
      of serum T levels but only an insignificant decline of DHT levels, independent of
      the dose. Serum and pituitary (p) luteinizing hormone (LH) levels in the ET
      treated rats did not change. Pituitary mRNA contents for the beta LH subunit
      (beta LH-mRNA) showed a dose-dependent significant increase, up to 170% (P <
      0.01), with ET treatment. pFSH decreased with the lowest ET (2 cm) dose (P <
      0.05), but no change was observed with the other doses. The mRNA for the common
      alpha-subunit also increased with the ET load. In conclusion, ET acts at several
      sites in the regulation of gonadotrophin formation and release. It enhances the
      steady-state mRNA levels of both gonadotrophins in the pituitary.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 7530292
TI  - NMDA and non-NMDA receptor-mediated release of [3H]GABA from granule cell
      dendrites of rat olfactory bulb.
AB  - We have studied the effect of glutamate and the glutamatergic agonists N-methyl-D
      aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) on [3H]GABA release from the external plexiform layer of
      the olfactory bulb. The GABA uptake blocker nipecotic acid significantly
      increased the basal [3H]GABA release and the release evoked by a high K+
      concentration, glutamate, and kainate. The glutamate uptake blocker pyrrolidine
      2,4-dicarboxylate (2,4-PDC) inhibited by 50% the glutamate-induced [3H]GABA
      release with no change in the basal GABA release. The glutamatergic agonists
      NMDA, kainate, and AMPA also induced a significant [3H]GABA release. The presence
      of glycine and the absence of Mg2+ have no potentiating effect on NMDA-stimulated
      release; however, when the tissue was previously depolarized with a high K+
      concentration, a significant increase in the NMDA response was observed that was
      potentiated by glycine and inhibited by the NMDA receptor antagonist 2-amino-5
      phosphonoheptanoic acid (AP-7). The kainate and AMPA effects were antagonized by
      the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but
      not by AP-7. The glutamate effect was also inhibited by CNQX but not by the NMDA
      antagonist 2-amino-5-phosphonopentanoic acid (AP-5); nevertheless, in the
      presence of glycine, [3H]GABA release evoked by glutamate was potentiated, and
      this response was significantly antagonized by AP-5. Tetrodotoxin inhibited
      glutamate- and kainate-stimulated [3H]GABA release but not the NMDA-stimulated
      release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530293
TI  - Effects of the serotonin1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin on
      neurochemical responses to stress.
AB  - The effects of intracerebroventricular administration of the 5-hydroxytryptamine
      (5-HT)1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 pmol) on
      adrenocortical and neurochemical responses to stress were examined in conscious
      male rats. The following stress paradigms were used: acoustic stimulation (105 dB
      for 2 min); footshock (0.2 mA, five shocks over 5 min); conditioned fear (animals
      placed in a footshock chamber for 5 min, 24 h after footshock); restraint (5
      min); intraperitoneal (i.p.) injection of recombinant human interleukin-1 alpha
      (rHu-IL-1 alpha, 20 micrograms/kg); and injection of cocaine hydrochloride (20
      mg/kg, i.p.). As previously shown, 8-OH-DPAT was able to attenuate the
      adrenocortical response to acoustic stress, conditioned fear, rHu-IL-1 alpha, and
      cocaine administration. Cocaine decreased 5-hydroxyindoleacetic acid (5-HIAA)/5
      HT and dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios and norepinephrine
      (NE) concentration in the prefrontal cortex, hypothalamus, and brainstem in all
      experiments, and 8-OH-DPAT reversed the changes in DOPAC/DA ratio without
      affecting 5-HIAA/5-HT ratios or NE content. 8-OH-DPAT alone had no effect on
      these parameters, although it decreased NE content in the prefrontal cortex in
      several experiments, and in the brainstem in one experiment. Significant
      decreases in NE content were observed in some brain regions following some of the
      stressors, but these changes were not generally affected by 8-OH-DPAT. Increases
      in the 5-HIAA/5-HT and DOPAC/DA ratios were also observed in some brain sites
      following some stressors, but these changes were not affected by 8-OH-DPAT except
      in the case of the increased 5-HIAA/5-HT ratio in the prefrontal cortex following
      the conditioned fear response. These results indicate that although 8-OH-DPAT is
      able to decrease plasma corticosterone responses following acoustic stress,
      conditioned fear, rHu-IL-1 alpha, and cocaine administration, these effects do
      not appear to be related to an action of the 5-HT1A agonist on biogenic amine
      metabolism. This observation indicates that the predominant effect of 8-OH-DPAT
      on adrenocortical responses is mediated at postsynaptic sites not involved in the
      regulation of cerebral biogenic amine metabolism.

PMID- 7530295
TI  - Myelin P0 glycoprotein: identification of the site phosphorylated in vitro and in
      vivo by endogenous protein kinases.
AB  - Myelin membrane prepared from mouse sciatic nerve possesses both kinase and
      substrates to incorporate [32P]PO4(3-) from [gamma-32P]ATP into protein
      constituents. Among these, P0 glycoprotein is the major phosphorylated species.
      To identify the phosphorylated sites, P0 protein was in vitro phosphorylated,
      purified, and cleaved by CNBr. Two 32P-phosphopeptides were isolated by HPLC. The
      exact localization of the sequences around the phosphorylated sites was
      determined. The comparison with rat P0 sequence revealed, besides a Lys172 to Arg
      substitution, that in the first peptide, two serine residues (Ser176 and Ser181)
      were phosphorylated, Ser176 appearing to be modified subsequently to Ser181. In
      the second peptide, Ser197, Ser199, and Ser204 were phosphorylated. All these
      serines are clustered in the C-terminal region of P0 protein. This in vitro study
      served as the basis for the identification of the in vivo phosphorylation sites
      of the C terminal region of P0. We found that, in vivo, Ser181 and Ser176 are not
      phosphorylated, whereas Ser197, Ser199, Ser204, Ser208, and Ser214 are modified
      to various extents. Our results strongly suggest that the phosphorylation of
      these serine residues alters the secondary structure of this domain. Such a
      structural perturbation could play an important role in myelin compaction at the
      dense line level.

PMID- 7530296
TI  - The simian virus 40 large T antigen does not inhibit translation of the 14-kDa
      myelin basic protein mRNA in reticulocyte lysates or in transfected cells.
AB  - Viral T antigens are transcription factors that have been suspected of inhibiting
      expression of the myelin basic protein (MBP) mRNA at the translational level in
      vitro and in vivo. The effect of simian virus 40 (SV40) large T antigen (T-ag)
      was examined on the translation of the 14-kDa MBP mRNA in reticulocyte lysates
      and on MBP expression after transfection into cells that express SV40 T-ag. SV40
      T-ag did not inhibit translation of 14-kDa MBP cRNAs in cell-free translations
      even at 30 microM (approximately 600 micrograms/ml) T-ag. Permanent transfection
      of COS-1 cells (which endogenously express SV40 T-ag) with the 14-kDa MBP cDNA
      resulted in the expression of the 14-kDa MBP as determined by western blot
      analysis. Permanent transfection of N20.1 cells, an oligodendrocyte line
      immortalized with a temperature-sensitive SV40 T-ag, with the 14-kDa MBP cDNA
      construct also resulted in the expression of the 14-kDa MBP under conditions in
      which the cells expressed functional SV40 T-ag. These results indicate that SV40
      T-ag does not prevent expression of the MBP gene at the translational level and
      that in those immortalized oligodendrocyte lines that express MBP mRNA, but not
      MBP protein, some factor other than the SV40 large T-ag is responsible for the
      posttranscriptional regulation.

PMID- 7530294
TI  - Effect of nerve growth factor and forskolin on glycosyltransferase activities and
      expression of a globo-series glycosphingolipid in PC12D pheochromocytoma cells.
AB  - The glycosphingolipid (GSL) composition of cells changes dramatically during
      cellular differentiation. Nerve growth factor (NGF) or forskolin (FRK) are known
      to induce cellular differentiation including process formation in PC12
      pheochromocytoma cells. In this respect, we present the NGF/FRK-dependent
      regulation of glycosyltransferase activities and the corresponding GSL expression
      in PC12D cells. After treatment of PC12D cells with NGF or FRK, the cell
      processes, including varicoses and growth cones, became strongly immunoreactive
      with an antibody against a unique globo-series neutral GSL, Gal alpha 1-3Gal
      alpha 1-4Gal beta 1-4Glc beta 1-1'Cer (GalGb3), and the activity of GalGb3
      synthase increased significantly. Other glycosyltransferase activities, including
      GM1 containing blood group B determinant (BGM1)-, GM3-, GD1a-, and GM2-synthases,
      also increased significantly upon NGF treatment, but the immunoreactivity against
      BGM1 did not show any appreciable change. For the parent PC12 cells, NGF/FRK
      treatment significantly increased the percentage of anti-GalGb3 positive cells
      and induced some immunoreactive cell processes. Because the parent PC12 cells do
      not express appreciable amounts of GalGb3, and because PC12D cells are considered
      to be more differentiated than the parent PC12 cells, the expression of GalGb3
      and the increase of GalGb3-synthase activity may be closely related to the
      cellular differentiation process in this cell line.

PMID- 7530297
TI  - Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against
      MPTP-induced neurotoxicity in mice.
AB  - Several studies suggest that nitric oxide (NO.) contributes to cell death
      following activation of NMDA receptors in cultured cortical, hippocampal, and
      striatal neurons. In the present study we investigated whether 7-nitroindazole (7
      NI), a specific neuronal nitric oxide synthase inhibitor, can block dopaminergic
      neurotoxicity seen in mice after systemic administration of MPTP. 7-NI dose
      dependently protected against MPTP-induced dopamine depletions using two
      different dosing regimens of MPTP that produced varying degrees of dopamine
      depletion. At 50 mg/kg of 7-NI there was almost complete protection in both
      paradigms. Similar effects were seen with MPTP-induced depletions of both
      homovanillic acid and 3,4-dihydroxyphenylacetic acid. 7-NI had no significant
      effect on dopamine transport in vitro and on monoamine oxidase B activity both in
      vitro and in vivo. One mechanism by which NO. is thought to mediate its toxicity
      is by interacting with superoxide radical to form peroxynitrite (ONOO-), which
      then may nitrate tyrosine residues. Consistent with this hypothesis, MPTP
      neurotoxicity in mice resulted in a significant increase in the concentration of
      3-nitrotyrosine, which was attenuated by treatment with 7 NI. Our results suggest
      that NO. plays a role in MPTP neurotoxicity as well as novel therapeutic
      strategies for Parkinson's disease.

PMID- 7530298
TI  - Neonatal cardiology casebook. Cardiac and noncardiac congenital defects palliated
      at the same operation.

PMID- 7530300
TI  - Perceptions of preschoolers' vulnerability by mothers who had delivered preterm.
AB  - Assessed mothers who did and did not identify their children as vulnerable on a
      number of variables including perception of their child's behavior problems and
      their own sense of parental control. Children were also examined to determine
      their developmental abilities. Participants included 50 preschoolers who were
      born prematurely, their mothers, and their medical care providers. The mothers'
      response to the Vulnerable Child Scale was used to identify children as
      vulnerable and nonvulnerable. Mothers who perceived their children as vulnerable
      also rated them on the Child Behavior Checklist 2/3 as having more somatic
      problems and as being more aggressive, destructive, and poorly socialized.
      Additionally, these mothers expressed a diminished sense of parental efficacy and
      less control of their child's behavior as measured by the Parental Locus of
      Control Scale. However, results from the McCarthy Scales of Children's Abilities
      and the medical care provider's questionnaire revealed no differences between the
      groups of children. Overall findings suggest preschoolers born prematurely whose
      mothers perceive them as vulnerable are at risk for the Vulnerable Child Syndrome
      described by Green and Solnit (1964).

PMID- 7530299
TI  - The preparation of an autologous saliva for use with patients undergoing
      therapeutic radiation for head and neck cancer.
AB  - PURPOSE: At the present time there is no general agreement about how to prevent
      the symptoms and clinical signs that accompany therapeutic irradiation for head
      and neck cancer. Because saliva is the principal protector of the oral tissues,
      it is logical to assume that many of these changes are due to the radiation
      induced damage to the salivary glands. We have observed that the flow and
      composition of saliva is normal in most patients before their irradiation.
      Theoretically, it should, therefore, be possible to collect their saliva before
      they commence their course of radiation, store it in a "saliva bank," and give it
      back to them when they undergo radiation. The key to the use of such an
      autologous saliva is the fabrication of a technique that disinfects or sterilizes
      the saliva yet preserves its protective properties. The objective of this study
      was to prepare an autologous saliva that would be used by patients during their
      irradiation for head and neck cancer. MATERIALS AND METHODS: Stimulated saliva
      was obtained from healthy subjects; none of the subjects consumed any
      medications. The saliva was treated by a variety of techniques. Included among
      them were heat, radiation, filtration, centrifugation, and an antibacterial
      agent. The samples were analyzed for total protein, amylase, viscosity, and
      sterility; individual salivary proteins were assessed by sodium dodecylsulfate
      polyacrylamide gel electrophoresis. RESULTS: The results showed that beta
      radiation (> 2.5 kGy) and lyophilization + chlorhexidine (0.03% to 0.12%) could
      be used to prepare a sterile autologous saliva that retained most of its
      protective properties.

PMID- 7530302
TI  - Synthesis, hydrolytic behavior, and anti-HIV activity of selected acyloxyalkyl
      esters of trisodium phosphonoformate (foscarnet sodium).
AB  - The synthesis and anti-HIV activity of selected (acyloxy)alkyl esters of
      trisodium phosphonoformate (foscarnet sodium) are described. The conversion of
      bis(trimethylsilyl) (alkoxycarbonyl)phosphonates 11a-d to the corresponding
      disilver salts 12a-d and their subsequent reaction with iodoalkyl acrylates 4a-c
      gave the desired bis(acyloxyalkyl) phosphonates 6-9(a-c). Of the analogs tested,
      only the dichlorophenyl analog 9a showed a dose-dependent inhibition of HIV
      activity in H9 cells. Using 31P-NMR, bioreversibility has been investigated in an
      attempt to rationalize these results.

PMID- 7530303
TI  - Glucocorticoid-dextran conjugates as potential prodrugs for colon-specific
      delivery: hydrolysis in rat gastrointestinal tract contents.
AB  - Chronic colitis, e.g., ulcerative colitis and Crohn's disease, is presently
      treated with glucocorticoids and other antiinflammatory agents. Side effects
      limit chronic glucocorticoid therapy. The dose, and consequently the side
      effects, may be reduced by using prodrugs that selectively deliver drug to the
      colon. We previously synthesized glucocorticoid-dextran conjugates in which
      dexamethasone and methylprednisolone were attached to dextran (weight-average
      molecular weight = 72,600) using dicarboxylic acid linkers (succinate and
      glutarate). In the present study, the hydrolysis kinetics of the hemiesters
      (hemiester = glucocorticoid+linker) and dextran conjugates were determined after
      incubation at 37 degrees C in diluted luminal contents of the gastrointestinal
      (GI) trace of male Sprague-Dawley rats. The hemiesters were rapidly hydrolyzed in
      the proximal small intestine (e.g., dexamethasone-hemiglutarate t1/2 = 0.5 h).
      This rate decreased progressively down the GI tract (t1/2 = 4.8, 54, and 68 h in
      distal small intestine, cecum, and colon, respectively). The enzyme responsible
      for hemiester hydrolysis, apparently a type-A alkaline carboxylesterase, is
      probably of host origin because its activity is highest in the small intestine
      where bacterial count is low. The dextran conjugates resisted hydrolysis in upper
      GI tract contents but were rapidly degraded in cecal and colonic contents where
      the bacterial count is high. The dextran conjugate tested, methylprednisolone
      succinate-dextran, was easily hydrolyzed by an endodextranase, indicating that
      substrate specificity is not lost upon the attachment of glucocorticoid. The
      results of this study indicate that dextran conjugates may be useful in
      selectively delivering glucocorticoids to the large intestine for the treatment
      of colitis.

PMID- 7530301
TI  - Effect of contignasterol on histamine release induced by anti-immunoglobulin E
      from rat peritoneal mast cells.
AB  - In rat peritoneal mass cells induced by anti-immunoglobulin E (anti-IgE),
      contignasterol (1) inhibited histamine release in a dose-dependent manner. On the
      other hand, a reduction product of contignasterol (2) did not inhibit histamine
      release from mast cells induced by anti-IgE.

PMID- 7530304
TI  - Quantitative structure-hydrophobicity and structure-activity relationships of
      antibacterial gramicidin S analogs.
AB  - The structure-hydrophobicity-antibacterial activity relationships of gramicidin S
      and its analogs retaining a beta-pleated sheet structure were examined
      quantitatively with physicochemical substituent and molecular parameters using
      regression analyses. Variations in their apparent hydrophobicity in an
      octanol/buffer (pH 7) system, log P' (O/W), were analyzed in terms of the
      "effective" hydrophobicity and steric parameters of side chain substituents of
      residues at certain positions in the molecule; however, some of the
      conformational factors have not been fully defined. For the partitioning into
      liposomes and the growth inhibitory activity against species of Gram-positive
      bacteria, the log P' (O/W) value simulated the hydrophobic effects of gramicidin
      S and its analogs better than substituent parameters. The side chain
      hydrophobicity was assumed to work together with effects attributed to variations
      in the entire cyclic peptide structure including conformational components
      undefined in the structure-log P' (O/W) analysis in these activities.

PMID- 7530305
TI  - [Single-dose toxicity study and twenty-eight-days intravenously repeated dose
      toxicity study of desethyl-piperacillin in rats].
AB  - Desethyl-piperacillin (desethyl-PIPC) is an active metabolite of PIPC which was
      newly found in clinical field. We carried out a single intravenous toxicity study
      at the dosage of 2000 mg/kg, and 28-days intravenous toxi-city study at the daily
      dosage of 400 mg/kg followed by 28-days recovery study using both sexes of rats.
      The following results were obtained. In the single dose toxicity study, no deaths
      occurred in rats injected 2000 mg/kg of desethyl-PIPC, therefore it is presumed
      that minimal lethal dose of desethyl-PIPC is over 2000 mg/kg in both sexes. As
      clinical signs, decrease in locomotor activity, deep breath and loose stool were
      observed. In the patho-logical study, dilatation of cecal lumen was observed
      macroscopically, but no significant changes were observed histologically. In the
      repeated dose toxicity study, loose stool, increase in water consumption,
      dilatation of cecal lumen and increase in its weight were noted. These abnormal
      findings were considered to be due to antimicrobial activity of desethyl-PIPC. In
      addition, decrease in the ratio of serum gamma-globulin and increase in the ratio
      of alpha 1-globulin were observed, but A/G ratio was not affected. After
      withdrawal of desethyl-PIPC administration, these abnormal findings tended to
      disappear. As mentioned above, the minimal lethal dose of desethyl-PIPC is over
      2000 mg/kg in the single dose toxicity study and abnormal signs were slight in
      the repeated dose toxicity study at the dosage of 400 mg/kg of desethyl-PIPC for
      28 days in rats. It is, therefore, concluded that desethyl-PIPC is a low toxic
      metabolite of PIPC.

PMID- 7530306
TI  - Effects of aspirin and indomethacin on ventricular arrhythmias--comparative
      study.
AB  - The effects of aspirin and indomethacin on the ventricular arrhythmias produced
      by ligation (ischaemia) and unligation (reperfusion) of the circumflex branch of
      the left coronary vessel were evaluated in fifty male rabbits weighing 1.5-2 kg.
      Pretreatment of animals with aspirin (50 mg/kg i/v) suppressed all arrhythmias
      during ischaemia. Low dose of aspirin (12.5 mg/kg i/v) produced no mortality.
      Indomethacin (2.5 mg/kg) was unable to control ischaemia and reperfusion-induced
      ventricular arrhythmias. However, higher doses of indomethacin (50 mg/kg)
      suppressed ischaemia-induced arrhythmias to some extent but the mortality rate
      was increased (37%). Fragment of ventricular fibrillation was zero during
      ischaemia after treatment with aspirin and indomethacin but reperfusion-induced
      ventricular fibrillation was not controlled by any of these drugs. Aspirin (12.5
      mg/kg, 50 mg/kg) and indomethacin (2.5 mg/kg) significantly suppressed ischaemia-
      induced tachyarrhythmias while reperfusion induced tachyarrhythmias were
      suppressed only by aspirin. There was no significant effect on the mean arterial
      pressure after these drug treatments.

PMID- 7530307
TI  - Surgery for T4 lung cancer: the prognoses of T4 lung cancer.
AB  - The prognoses of T4 lung cancer patients treated surgically were investigated in
      76 patients. Extended resection was performed in 21 patients, palliative
      resection in 21 and exploratory thoracotomy in 34. Although the five-year
      survival of the extended resection group did not differ significantly from that
      obtained in the exploratory thoracotomy group, the mean survival time of the
      extended resection group was 3.1 months longer than that of the exploratory
      thoracotomy group. Two patients who had undergone resection for left atrial
      involvement, survived for two years or more, and a T4N0 patient with squamous
      cell carcinoma, in whom resection for aortic involvement was carried out, died
      from an unrelated disease after 15 months. Two patients with pleural
      dissemination, who underwent panpleuropneumonectomy, survived for two years.
      Surgical intervention did not improve the prognosis of patients with N2-squamous
      cell carcinoma, those with malignant effusion or those with multiple organ
      involvement.

PMID- 7530308
TI  - Parachordoma of the buttock: an immunohistochemical case study and review.
AB  - We report a case of parachordoma occurring in the buttock of a 43-year-old man,
      and review 20 cases of parachordoma reported in the English literature. The tumor
      in our case was grossly 3 cm in dimension, solid, lobulated and grayish-white in
      color. Microscopically, the tumor consisted of epithelioid and spindle cells, and
      fibromyxoid stroma. The epithelioid cells were immunohistochemically positive for
      vimentin, S-100 protein, neuron-specific enolase, keratin, carcinoembryonic
      antigen and epithelial membrane antigen, and negative for HMB45. These findings
      are similar to those for chordoma rather than extraskeletal myxoid
      chrondrosarcoma. Although the etiopathogenesis of parachordoma remains obscure,
      Schwann cells or some other neuron-related cell origin are suspected.

PMID- 7530309
TI  - Ligation-induced acute pancreatitis in opossums: acinar cell necrosis in the
      absence of colocalization.
AB  - Acute necrotizing pancreatitis in opossums after bile and pancreatic duct
      ligation (BPDL) is a useful experimental corollary of gallstone-induced acute
      pancreatitis in humans. In experimental and human acute pancreatitis, a loss of
      segregation of the lysosomal enzyme cathepsin B and the zymogen proenzyme
      trypsinogen (colocalization) is implicated as the triggering event of disease
      pathogenesis, as cathepsin B can activate trypsinogen. The object of this study
      was to quantitate acinar cell necrosis and to study subcellular distribution of
      cathepsin B in BPDL-induced acute necrotizing pancreatitis in opossums. Bile and
      pancreatic ducts were ligated separately (no bile reflux) in four opossums while
      ducts were dissected in four sham controls. Opossums were killed 24 hr after
      operation. Three equidistant cross-sectional portions of each opossum pancreas
      were submitted to histologic examination. In blinded fashion, each focus of
      acinar cell necrosis was photographed and quantitated with digitizing
      morphometry. Numerical density (foci/cm2) and areal density (x10(3) micron 2/cm2)
      of focal acinar cell necrosis were determined. Differentially centrifuged
      pancreatic homogenates were assayed for cathepsin B, the lysosomal marker enzyme
      N-acetylglucosaminidase, and amylase. Morphometric quantitation of acinar cell
      necrosis confirmed development of acute necrotizing pancreatitis after 24 hr of
      BPDL in opossums. However, colocalization was not observed after BPDL, as
      evidenced by an absence of subcellular shift of cathepsin B activity (and N
      acetyl-glucosaminidase activity) from the lysosome-enriched to the zymogen
      enriched subcellular fraction. Amylase activity was increased in subcellular
      fractions after BPDL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530312
TI  - Endogenous mediators in adaptive cytoprotection against ethanol-induced gastric
      gland damage in rabbits.
AB  - The present study determined the participation of different endogenous mediators
      in adaptive cytoprotection against gastric gland damage caused by ethanol in
      rabbits. Using the isolated gland preparation, pretreatment with 10(-5)M of
      either indomethacin, Nw-nitro-L-arginine methyl ester (L-NAME) or N
      ethylmaleimide (NEM), but not of substance P antagonist, intensified the 10%
      (v/v) ethanol-induced gastric gland damage and lessened the degree of
      cytoprotection evoked by 2% (v/v) ethanol to a significant level. Co
      administration with 10(-4)M of prostaglandin E2, L-arginine or glutathione to the
      respective groups completely reversed the above adverse effects. These results
      demonstrate the involvement of endogenous prostaglandins, nitric oxide and
      glutathione in gastric adaptive cytoprotection against the damaging action of
      ethanol in the rabbit gastric glands.

PMID- 7530310
TI  - Adrenergic and cromolyn sodium modulation of ECL cell histamine secretion.
AB  - The histamine secreting enterochromaffin-like (ECL) cell is now recognized as the
      principal regulator of gastric acid secretion. Histamine is not only a primary
      modulator of acid secretion, but may be of relevance in gastritis and as a
      mitogen in gastric neoplasia. Study of the ECL cell has been limited since no
      pure preparation was available. We therefore developed a pure isolated ECL cell
      preparation with a purity of 90-95% as determined by total histamine content and
      chromogranin immunofluorescence. Trypan blue exclusion demonstrated > 95%
      viability. While gastrin and acetylcholine are known modulators of acid
      secretion, the role of adrenergic neurotransmitters has not been clearly
      delineated. The purpose of this study was to examine adrenergic modulation of ECL
      cell histamine release. To further define the inhibitory mechanisms of histamine
      secretion, we evaluated the mast cell histamine inhibitor sodium cromoglycate.
      Histamine secretion was determined by radioimmunoassay. Basal secretion was 0.6
      +/- 0.2 nmol/10(3) cells. Gastrin stimulated histamine secretion with an EC50 of
      3 x 10(-10) M. Octopamine (alpha-adrenergic agonist) (10(-11)-10(-4) M) failed to
      stimulate histamine secretion. Isoproterenol (beta-adrenergic agonist) stimulated
      histamine secretion (EC50, 6 x 10(-8) M) and was inhibited by propranolol (IC50 5
      x 10(-10) M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530311
TI  - Concepts and progress in the development and utilization of receptor-specific
      fluorescent ligands.

PMID- 7530313
TI  - Alpha-fetoprotein binding proteins: implications for transmembrane passage and
      subcellular localization.
AB  - Alpha-fetoprotein (AFP) is an oncofetal protein classified in a super-family
      together with albumin and Vitamin-D binding (Gc) protein which present as
      globular proteins comprised of three domains. Several subdomain regions on AFP
      have been previously proposed to serve as dimerization interfaces for nuclear
      receptors or perhaps other co-factors/inhibitors. The cellular uptake and
      internalization of AFP together with its subcellular compartmentalization is now
      well documented in a variety of cell types. A myriad of reports have emerged
      which have detected, identified, and characterized various binding proteins
      associated with AFP in different cellular compartments. However, the literature
      is devoid of any attempts to summarize, categorize, and relate these proteins to
      the various physiological activities attributed to this fetal protein. It is
      conceivable that AFP could interact and/or bind cytoplasmic chaperone proteins
      that normally escort nuclear factors or transcription co-factors through the
      cytoplasm toward organelle interfaces. A dual concept proposing binding or escort
      proteins for AFP together with subdomain dimerization interfaces on the AFP
      molecule can be reconciled into a composite hypothesis to formulate a rationale
      for the growth regulating properties ascribed to AFP during the last decade.
      Thus, AFP might serve as a modulator/modifier of various cell growth regulatory
      pathways during embryonic and fetal development in vertebrates.

PMID- 7530314
TI  - Effect of streptozotocin-induced diabetes mellitus on serotonin measures of
      peripheral tissues in rats.
AB  - The present study was conducted to examine whether experimental diabetes
      (streptozotocin-induced) promotes changes in serotonin (5HT) measures of
      peripheral tissue. Platelet-free plasma 5HT, tryptophan and 5-hydroxyindolacetic
      acid (5HIAA), whole blood 5HT and renal, liver, intestinal and lung 5HT and 5HIAA
      levels were measured in rats of four experimental groups: control, diabetic,
      diabetic+insulin and non-diabetic+insulin. Several serotonin measures were
      unaltered in all four experimental groups, i.e. plasma, liver and lung 5HT and
      5HIAA levels. Whole blood 5HT levels descended about 50% in diabetic rats, then
      recovered their proper levels after 1 week of insulin therapy. Diabetic animals
      had a significantly greater intestinal 5HT concentration (+50% versus control),
      while intestinal 5HIAA levels did not achieve statistical significance despite a 
      26% decrement in their value. Both renal 5HT and 5HIAA levels were decreased in
      diabetic animals and recovered with insulin therapy. Peripheral tissue 5HT
      measures were not varied by insulin administration to non-diabetic animals. The
      results are consistent with a 5HT release, which is diminished in
      enterochromaffin cells and enhanced in platelet concomitantly to a minor platelet
      5HT uptake, for explaining alterations of plasma/blood 5HT measures in
      experimental diabetes, and with a diminished synthesis of 5HT for explaining
      renal changes.

PMID- 7530315
TI  - Extracellular dopamine and its metabolites in the nucleus accumbens of Fischer
      and Lewis rats: basal levels and cocaine-induced changes.
AB  - Rats of the Lewis (LEW) strain show a greater preference for drugs of abuse than
      do Fischer 344 (F344) rats. The in vivo microdialysis procedure was used to
      examine basal and cocaine-evoked extracellular (EC) levels of dopamine (DA),
      DOPAC, and HVA in the nucleus accumbens (NAc) of F344 and LEW rats. The basal EC
      levels of the DA metabolites DOPAC and HVA in the NAc were markedly lower in LEW
      than in F344 rats. Although the increase in EC DA after 3, 10, or 30 mg/kg, i.p.
      of cocaine was similar in both strains, LEW rats had a smaller peak DA elevation
      followed by a slower return to basal DA levels at the 30 mg/kg dose. The
      neurochemical differences observed may contribute to the strain differences in
      the behavioral response to cocaine.

PMID- 7530316
TI  - Distinct mechanisms of interactions of Opc-expressing meningococci at apical and
      basolateral surfaces of human endothelial cells; the role of integrins in apical
      interactions.
AB  - Interactions of Opc-expressing Neisseria meningitidis with polarized and non
      polarized human umbilical vein endothelial cells (Huvecs) were investigated.
      Metabolic inhibitors and cytochalasin D treatment showed that host cellular and
      cytoskeletal functions were important for Opc-expressing bacterial association
      with Huvecs at the apical surface. In addition, this interaction required the
      presence of serum in the incubation medium whilst association with non-polarized
      cells did not require serum. Pre-exposure of Opc-expressing bacteria to serum was
      sufficient to increase the number of bacterial interactions at the apical
      surface; B306, a monoclonal antibody (mAb) against Opc, inhibited these
      interactions, suggesting that Opc binds to serum factor(s) and this in turn
      increases adherence to Huvecs. The receptors involved in this 'sandwich'
      adherence belong to the integrin family since the interaction was inhibited by
      peptides containing the amino acid sequence arginine-glycine-aspartic acid (RGD)
      and the tetrapeptide RGDS (but not the peptide RGES) was inhibitory. Non
      polarized cells appeared to expose receptors/sites that bound to Opc-expressing
      bacteria directly, did not require serum factors and were not inhibited by RGD
      containing peptides. Serum-dependent interactions of Opc-expressing bacteria to
      apical surface was inhibited significantly by several mAbs against alpha v beta 3
      integrins. Some mAbs against alpha 5 and beta 1 caused partial inhibition;
      antibodies that did not block the function of beta 1 integrins or the mAbs
      against alpha 2 integrins were not inhibitory to bacterial interactions with
      Huvecs. Purified vitronectin supported adherence of Opc-expressing bacteria to
      Huvecs but not of Opc- bacteria. These interactions were inhibited by mAb B306
      against Opc, by RGDS peptides as well as by blocking antibodies directed against
      alpha v beta 3 but not antibodies against other integrins. These data suggest
      that a sequence of molecular events resulting in trimolecular complexes at the
      endothelial surface may drive neisserial invasion of Huvecs. The expression of
      Opc appears to enable bacteria to utilize the normal signal-transduction
      mechanism of host cells via ligands in sera that adhere to endothelial cell
      integrins.

PMID- 7530319
TI  - Using maximum likelihood spectral deconvolution in multidimensional nuclear
      magnetic resonance.

PMID- 7530318
TI  - Characterization of trimethoprim- and sulphisoxazole-resistant Chlamydia
      trachomatis.
AB  - Trimethoprim and sulphisoxazole were used as selective agents in culture to
      isolate, by a stepwise procedure, a series of Chlamydia trachomatis L2
      populations resistant to the cytotoxic effects of the drugs. Two trimethoprim
      resistant populations, L2TriR-60 and L2TriR-100, and one sulphonamide-resistant
      population, L2SulfR-100, were characterized in more detail. In addition to being
      resistant to trimethoprim, L2TriR-60 was cross-resistant to methotrexate,
      sensitive to sulphisoxazole and displayed a ribonucleotide auxotrophy similar to
      that of its parental wild type, C. trachomatis L2. Surprisingly, L2TriR-100 and
      L2SulfR-100 appeared phenotypically identical. Both mutants were highly resistant
      to trimethoprim, sulphisoxazole, and methotrexate. In contrast to wild-type C.
      trachomatis L2, these populations were sensitive to 5-fluorouracil. L2TriR-100
      and L2SulfR-100 were incapable of taking pyrimidine ribonucleotides from the host
      cell and no longer synthesized thymidine nucleotides de novo. The pyrimidine
      requirement of these mutants was met by salvaging host-cell uracil and thymidine,
      a property which can account for their drug-resistant characteristics. L2TriR-100
      and L2SulfR-100 could also salvage adenine and guanine. Using L2TriR-100 as a
      starting stock, a mutant population resistant to the cytotoxic effects of
      trimethoprim and 5-fluorouracil (L2Tri/5-FU) was selected. L2Tri/5-FU was
      resistant to 5-fluorouracil because it had regained the capacity to take
      pyrimidine ribonucleotides from the host cell.

PMID- 7530317
TI  - Identification and characterization of an intervening sequence within the 23S
      ribosomal RNA genes of Campylobacter jejuni.
AB  - Campylobacter jejuni is a significant cause of bacterial enteritis in humans.
      Three of seven C. jejuni isolates examined were found to contain fragmented 23S
      rRNA. The occurrence of fragmented 23S rRNA correlated with the presence of an
      intervening sequence (IVS) within the 23S rRNA genes. The IVS is 157 nucleotides
      in length and replaces an eight nucleotide sequence in the 23S rRNA genes of C.
      jejuni isolates that contain intact 23S rRNA. The two ends of the IVS share 31
      bases of complementarity that could form a stem-loop structure. Fragmentation of
      the 23S ribosomal RNA results from the excision of the IVS from the transcribed
      RNA; the 3' cleavage site maps within the putative stem-loop formed by the IVS.
      Southern hybridization analysis revealed that the IVS is not present in the
      genomes of isolates that contain intact 23S rRNA, suggesting that the IVS is not
      derived from Campylobacter chromosomal sequences. The C. jejuni IVS is located at
      a position analogous to that of the IVSs found in both Salmonella and Yersinia
      spp.

PMID- 7530321
TI  - Nuclear magnetic resonance methods for studying protein-ligand complexes.

PMID- 7530322
TI  - Prostate-specific antigen--is it already being used as a screening test?

PMID- 7530320
TI  - Accounting for molecular mobility in structure determination based on nuclear
      magnetic resonance spectroscopic and X-ray diffraction data.

PMID- 7530323
TI  - Effect of cigarette smoke on the mutagenic activation of various carcinogens in
      hamster.
AB  - Male Syrian golden hamsters were exposed for 1 or 2 weeks to smoke produced by
      commercial non-filter cigarettes for 5 consecutive days in a Hamburg type II
      smoking machine. Postmitochondrial fractions (S9) prepared from the liver, lungs,
      and pancreas were used in the Ames liquid incubation assay, in order to assess
      the effect of cigarette smoke (CS) on the metabolic activation of four groups of
      procarcinogens. The mutagenic activities of five heterocyclic amines on strain
      TA98 in the presence of liver S9 mix were induced up to 3.7 times above controls
      including sham smoke control, while no significant alteration of mutagenicity was
      observed with 3'-hydroxymethyl-N,N-dimethyl-4-aminoazobenzene and benzo[a]pyrene
      on TA98 or with N-nirosobis(2-oxopropyl)amine (BOP) on TA100. A similar
      stimulation of metabolic activation was also observed for 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole (Trp-P-1) with S9 from the lungs but not from the pancreas.
      The mutagenic potential of 11 carcinogens including aflatoxin B1 (AFB1) and two
      other heterocyclic amines was also examined using liver S9 from male hamsters
      pretreated with phenobarbital (PB) or 3-methylcholanthrene (MC). The numbers of
      revertant colonies were much higher (2-20-fold) in the presence of MC-treated
      liver S9 than in the presence of PB-treated liver S9, except in the case of AFB1
      which showed a higher mutagenicity with PB-induced S9. 7,8-Benzoflavone
      considerably inhibited the activities of 2-amino-3-methylimidazo[4,5-f]quinoline
      (IQ) and Trp-P-1 in the presence of either untreated, MC- or CS-treated liver S9,
      whereas metyrapone was totally lacking this effect, indicating that cytochrome
      P450(CYP)1A1/1A2 isoforms of hamster liver are predominantly involved in the
      metabolic activation of these carcinogens. CS exposure of hamsters might
      selectively induce hepatic CYP1A2 which cannot activate BOP. Consequently, the
      present findings could explain, in part, the anticarcinogenic effect of CS on BOP
      induced pancreatic tumors in hamsters. The findings further support the idea that
      CS markedly stimulates the metabolic activation of food-derived carcinogens,
      which may contribute to the overall carcinogenic effects of cigarette smoking.

PMID- 7530324
TI  - Heavy metals enhance the reactivation of nitrous acid-treated adenovirus in HeLa
      cells.
AB  - Treatment of HeLa cells with cadmium chloride and zinc chloride increases the
      survival rate of nitrous acid-treated adenovirus 2 (ade2). This increase is
      maximal if the time interval between cell treatment and virus infection is
      delayed by 36 h. The induction process requires protein synthesis only during the
      3-h period immediately following treatment; cycloheximide does not prevent the
      expression of enhanced reactivation if added to the cells after this time.

PMID- 7530325
TI  - Evidence for the protective effect of ascorbic acid (vitamin C) in treatment with
      gamma-rays and chromium (VI) oxide (CrO3) in somatic cells of Drosophila.

PMID- 7530326
TI  - Melatonin protects human blood lymphocytes from radiation-induced chromosome
      damage.
AB  - Cells in human peripheral blood were treated in vitro with increasing
      concentrations of melatonin (0.5 or 1.0 or 2.0 mM) for 20 min at 37 +/- 1 degrees
      C and then exposed to 150 cGy gamma-radiation from a 137Cs source. The
      lymphocytes which were pre-treated with melatonin exhibited a significant and
      concentration-dependent decrease in the frequency of radiation-induced chromosome
      damage as compared with the irradiated cells which did not receive the pre
      treatment. The extent of the reduction in radiation-induced chromosome damage
      observed with 2.0 mM melatonin was similar to that found in lymphocytes pre
      treated with 1.0 M dimethyl sulfoxide, a known free radical scavenger. Melatonin
      at 2.0 mM (a 500 x lower concentration) was as effective in decreasing the
      radiation-induced chromosome damage as dimethyl sulfoxide at 1.0 M. These
      observations may have implications for human protection against damage due to
      endogenously produced free radicals and also due to exposure to free radical
      producing physical and chemical mutagens and carcinogens.

PMID- 7530328
TI  - Effect of carboxymethyl-chitin-glucan on cyclophosphamide induced mutagenicity.
AB  - The effect of high molecular carboxymethyl-chitin-glucan (CMCG), administered
      either intraperitoneally, intravenously or orally prior to cyclophosphamide
      injection, on the frequency of micronucleated reticulocytes was evaluated in
      peripheral blood of female ICR mice. Both intraperitoneal and intravenous
      administration of CMCG decreased the clastogenic effect of cyclophosphamide. The
      protective effect of CMCG was concentration dependent, with a higher decrease
      achieved by 100 mg/kg than by 50 mg/kg body weight. On the other hand, not even
      five peroral pretreatments with CMCG in the dose of 200 mg/kg body weight during
      the week prior to simultaneous administration of CMCG and cyclophosphamide
      induced a decrease of micronucleated reticulocytes in peripheral blood. It is
      therefore conceivable that CMCG failed to pass through the gastrointestinal
      tract, probably due to its high molecular weight. The antimutagenic effect of
      CMCG against cyclophosphamide was manifested by its intraperitoneal and
      intravenous administration to female ICR mice.

PMID- 7530327
TI  - Adriamycin-inducible proteins associated with drug sensitivity in resistant
      immunoblastic B lymphoma cells.
AB  - We have previously established an immunoblastic B lymphoma cell line, designated
      HOB1. This cell line is hypersensitive to a wide spectrum of chemotherapeutic
      agents. Two co-regulated polypeptides around 64 kDa (termed p64) were induced 10
      30-fold in response to adriamycin and some other drugs at the IC50 (the
      concentration inhibiting cell growth by 50%). These inducible proteins are
      localized as monomeric forms in the cytosolic fraction, with isoelectric points
      of pH = 6.2 (major protein) and pH = 7.0 (minor protein). An adriamycin-resistant
      cell line was established from HOB1 cells. The p64 inducibility was dramatically
      reduced in resistant HOB1 cells or unrelated cell lines which show phenotypic
      resistance to adriamycin toxicity. The loss of p64 inducibility in resistant
      cells is not due to a failure of cells to take up adriamycin since drug
      accumulation kinetics remained the same as in the parental cells.

PMID- 7530329
TI  - Genotoxic effects of chemicals in the single cell gel (SCG) test with human blood
      cells in relation to the induction of sister-chromatid exchanges (SCE).
AB  - In a comparative study, benzo[a]pyrene (BaP), cyclophosphamide (CP), N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG) and tetrachloroethylene (PER) were tested for
      their ability to induce genotoxic effects in the single cell gel (SCG) test and
      the sister-chromatid exchange (SCE) test with human blood cells. MNNG as well as
      S9 mix activated BaP- and CP-induced DNA effects in both tests in a dose
      dependent manner. While the range of concentrations which induced DNA migration
      or SCE was the same for MNNG and for BaP, much higher CP concentrations were
      necessary for a positive response in the SCG test than in the SCE test. PER was
      tested in the absence and in the presence of S9 mix and neither induced DNA
      migration nor increased SCE frequencies. In these experiments, a clear cytotoxic
      effect of PER was observed. To investigate a possible influence of DNA repair on
      the effects in the SCG test, cells were treated for 2 h and further incubated for
      1 h after removal of the test substance. This procedure caused a clear decrease
      in induced DNA migration in experiments with BaP and CP, whereas no reduction was
      found with MNNG. This modified protocol did not lead to the detection of DNA
      effects after treatment with PER. The results indicate that the SCG test responds
      to various DNA lesions and does not seem to be sensitive to non-genotoxic cell
      killing. Its sensitivity obviously depends on the type(s) of induced DNA lesions
      and the effects can be modified by DNA repair processes in a complex manner. For
      the detection of genotoxic properties of chemicals with the in vitro SCG test, a
      single evaluation at the end of the exposure period seems to be sufficient.

PMID- 7530330
TI  - Detection of mutagenicity of diphenyl ether herbicides in Salmonella typhimurium
      YG1026 and YG1021.
AB  - Three kinds of diphenyl ether herbicides, 4-nitrophenyl 2,4,6-trichlorophenyl
      ether (CNP, chlornitrofen), 2,4-dichlorophenyl 3-methoxy-4-nitrophenyl ether
      (chlomethoxynil) and 2,4-dichlorophenyl 3-methoxycarbonyl-4-nitrophenyl ether
      (bifenox), were tested for mutagenicity in Salmonella typhimurium YG1026 and
      YG1021, which have high nitroreductase activity, and also in S. typhimurium TA100
      and TA98. CNP and chlomethoxynil showed mutagenicity in S. typhimurium YG1026,
      without S9 mix, inducing 50 and 304 revertants per microgram. These
      mutagenicities were suppressed by the addition of S9 mix. CNP and chlomethoxynil
      were also mutagenic to YG1021 with and without S9 mix, and their mutagenicities
      were lower than those to YG1026. On the other hand, bifenox was mutagenic to
      YG1026 only with S9 mix, inducing 3.0 revertants per micrograms. These three
      herbicides showed no mutagenicity in S. typhimurium TA100 and TA98 either with or
      without S9 mix.

PMID- 7530331
TI  - Inducible stable DNA replication of Escherichia coli tolerates unexcised
      pyrimidine dimers in an uvr-dependent manner.
AB  - Damage-inducible DNA replication (iSDR) was followed in UV-irradiated E. coli
      uvr+ and uvr B5 cells. Owing to the inhibition of dimer excision in the former
      (caused by the metabolic treatment), both contained similar amounts of unexcised
      dimers. Since the iSDR took place in uvr+ but not in uvr B5 cells, it is
      concluded that the uvr system can tolerate unexcised dimers through the
      recombinogenic iSDR.

PMID- 7530332
TI  - Structure of NF-kappa B p50 homodimer bound to a kappa B site.
AB  - The 2.3-A crystal structure of the transcription factor NK-kappa B p50 homodimer
      bound to a palindromic kappa B site reveals that the Rel homology region folds
      into two distinct domains, similar to those in the immunoglobulin superfamily.
      The p50 dimer envelopes an undistorted B-DNA helix, making specific contacts
      along the 10-base-pair kappa B recognition site mainly through loops connecting
      secondary structure elements in both domains. The carboxy-terminal domains form a
      dimerization interface between beta-sheets using residues that are strongly
      conserved in the Rel family.

PMID- 7530333
TI  - W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker
      activity.
AB  - The pacemaker activity in the mammalian gut is responsible for generating anally
      propagating phasic contractions. The cellular basis for this intrinsic activity
      is unknown. The smooth muscle cells of the external muscle layers and the
      innervated cellular network of interstitial cells of Cajal, which is closely
      associated with the external muscle layers of the mammalian gut, have both been
      proposed to stimulate pacemaker activity. The interstitial cells of Cajal were
      identified in the last century but their developmental origin and function have
      remained unclear. Here we show that the interstitial cells of Cajal express the
      Kit receptor tyrosine kinase. Furthermore, mice with mutations in the dominant
      white spotting (W) locus, which have cellular defects in haematopoiesis,
      melanogenesis and gametogenesis as a result of mutations in the Kit gene, also
      lack the network of interstitial cells of Cajal associated with Auerbach's nerve
      plexus and intestinal pacemaker activity.

PMID- 7530334
TI  - Apoptosis. Death of a T cell.

PMID- 7530335
TI  - Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)
AB  - The APO-1/(Fas/CD95) cell surface receptor is a member of the nerve growth factor
      (NGF)/tumour necrosis factor (TNF) receptor superfamily and mediates apoptosis.
      Peripheral activated T cells (ATC) from lymphoproliferation (lpr/lpr) mutant mice
      that express a reduced number of APO-1 receptors have a defect in T-cell receptor
      (TCR)-induced apoptosis. This suggests that TCR-induced apoptosis involves APO-1.
      We tested this hypothesis in various human T cells: (1) malignant Jurkat cells,
      (2) an alloreactive T-cell clone (S13), and (3) peripheral ATC. TCR triggering
      through immobilized anti-CD3 antibodies or Staphylococcus enterotoxin B (SEB)
      superantigen induced expression of the APO-1 ligand and apoptosis in these cells.
      Anti-CD3-induced apoptosis of Jurkat cells was demonstrated even in single-cell
      cultures. In all cases apoptosis was substantially inhibited by blocking anti-APO
      1 antibody fragments and soluble APO-1 receptor decoys. The APO-1 ligand was
      found in the supernatant of activated Jurkat cells as a soluble cytokine. We
      propose that TCR-induced apoptosis in ATC can occur through an APO-1 ligand
      mediated autocrine suicide. These results provide a mechanism for suppression of
      the immune response and for peripheral tolerance by T-cell deletion.

PMID- 7530336
TI  - Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced
      apoptosis in T-cell hybridomas.
AB  - A number of murine T-cell hybridomas undergo apoptosis within a few hours of
      activation by specific antigens, mitogens, antibodies against the T-cell antigen
      receptor, or a combination of phorbol ester and calcium ionophore. This
      phenomenon has been extensively studied as a model for clonal deletion in the
      immune system, in which potentially autoreactive T cells eliminate themselves by
      apoptosis after activation, either in the thymus or in the periphery. Here we
      show that the Fas/CD95 receptor, which can transduce a potent apoptotic signal
      when ligand, is rapidly expressed following activation of T-cell hybridomas, as
      is its functional, membrane-bound ligand. Interference with the ensuing Fas/Fas
      ligand interaction inhibits activation-induced apoptosis. Because T-cell receptor
      ligation can induce apoptosis in a single T hybridoma cell, we suggest that the
      Fas/Fas-ligand interaction can induce cell death in a cell-autonomous manner.

PMID- 7530338
TI  - [To the hospital or not? A dilemma in nursing home medicine].

PMID- 7530337
TI  - Fas(CD95)/FasL interactions required for programmed cell death after T-cell
      activation.
AB  - Receptor crosslinking of T-cell hybridomas induces cell activation followed by
      apoptosis. This activation-induced cell death requires de novo synthesis of RNA
      and proteins, but the actual gene products that provide the death signal have not
      been identified. We show here that receptor crosslinking induces Fas ligand and
      upregulates Fas, and that the ensuing engagement of Fas by Fas ligand activates
      the cell-death programme. Cell death, but not activation, can be selectively
      prevented by a soluble Fas-immunoglobulin fusion protein. Thus, Fas and Fas
      ligand are the death-gene products, and their interaction accounts for the
      molecular mechanism of activation-induced T-cell death.

PMID- 7530339
TI  - [The effect of the nervous system on joint inflammations].

PMID- 7530340
TI  - Neutrophil adhesion molecules in chronic hemodialysis patients.
AB  - The expression of the adhesion molecules LFA-1 (CD11a-CD18), Mac-1 (CD11b-CD18),
      and LAM-1 on predialysis and intradialysis neutrophils (PMN) was analyzed by flow
      cytometry in 10 chronic hemodialysis patients (CHD) and compared with age-matched
      normal controls. All patients were dialyzed either with a polyacrylonitrile, or a
      polysulfone membrane. To appreciate the influence of the interdialytic time, we
      compared the samples of Monday (3 days without dialysis), with those of Wednesday
      (2 days without dialysis). A patient group not treated with recombinant human
      erythropoietin (rHuEPO) was also included to analyze the influence of r-HuEPO. We
      found on the predialysis and intradialysis samples that the expression of CD11a
      was not different in the CHD patients and in the normal controls. Hemodialysis
      was associated with a rapid and significant reduction in LAM-1 on the 15- and 30
      min samples (p < 0.05). This reduction was only transient, and returned to near
      predialysis levels after 120 min dialysis. The MAC-1 increased significantly
      after 30 min dialysis (p < 0.01), and remained at the end of the dialysis
      procedure still substantially above the predialysis levels (p < 0.01). On the
      other hand, we have found a significant (p < 0.005) up-regulating of the MAC-1,
      and a down-regulating of the LAM-1 in the predialysis samples. We noticed further
      a significantly lower expression (82 +/- 9.6%) for LAM-1 in these predialysis
      samples (p < 0.005). These results demonstrate that 'high MAC-1, low LAM-1'
      neutrophils were not only a dialysis-related phenomenon, but that they were
      already present before the hemodialysis session, nor was there any difference
      between the interdialytic times or compared with the r-HuEPO treatment.

PMID- 7530343
TI  - Deficits in sciatic nerve neuropeptide content coincide with a reduction in
      target tissue nerve growth factor messenger RNA in streptozotocin-diabetic rats:
      effects of insulin treatment.
AB  - The role of sub-optimal neurotrophic support in the aetiology of the sensory
      neuron dysfunction associated with diabetic neuropathy was investigated. The
      status of sciatic nerve neuropeptide content was related to target tissue nerve
      growth factor messenger RNA levels in streptozotocin-diabetic rats. The levels of
      substance P and calcitonin gene-related peptide in diabetic sciatic nerve were
      significantly lowered by approximately 50% and 28%, respectively, compared with
      aged matched controls and insulin-treated diabetic rats (P < 0.01) for both
      peptides and both comparisons). Measurements of nerve growth factor messenger RNA
      levels in sensory neuron target tissues, namely foot-skin and soleus muscle,
      revealed deficits of approximately 50% in diabetic rats, with insulin treatment
      reversing the decrease in foot-skin but not in soleus muscle. The results show a
      possible correlation between deficient neuropeptide gene expression in sensory
      neurons and reduced nerve growth factor messenger RNA levels in target tissue.

PMID- 7530342
TI  - Nerve growth factor contributes to the generation of inflammatory sensory
      hypersensitivity.
AB  - Experimental inflammation produced by an intraplantar injection of complete
      Freund's adjuvant results in local sensory hypersensitivity and up-regulates the
      neuropeptides substance P and calcitonin gene related peptide in the primary
      sensory neurons innervating the inflamed tissue. The inflammation also elevates
      nerve growth factor levels in the skin. Systemic administration of anti-NGF
      neutralizing antibodies prevent the behavioral sensitivity, the up-regulation of
      neuropeptides and the inflammation-induced expression of the immediate early gene
      c-fos in dorsal horn neurons, without modifying swelling and erythema. Elevation
      of the neurotrophin NGF in the periphery is a major contributor, therefore, of
      inflammatory pain.

PMID- 7530341
TI  - Detection of glycosylated protein in renal tissues and dermal vascular vessels in
      the microalbuminuric stage of diabetic nephropathy using the nitro blue
      tetrazolium reaction.
AB  - Detection of glycosylated protein in renal and dermal tissues was performed in
      patients in the microalbuminuric stage of diabetic nephropathy using the nitro
      blue tetrazolium (NBT) reaction. The intensity of NBT staining in glomeruli and
      dermal vascular vessels was marked in the microalbuminuric stage as well as in
      the overtly proteinuric stage. The NBT staining in the renal and dermal vascular
      walls in both stages was significantly stronger than in the samples of control
      autopsy patients. It appeared that nonenzymatic glycosylation in various tissues,
      i.e. kidneys and dermal vascular vessels, had already progressed in the
      microalbuminuric stage in patients with diabetic nephropathy.

PMID- 7530345
TI  - A direct pretectosuprachiasmatic projection in the rat.
AB  - The major afferent projections of the suprachiasmatic nuclei originate in the
      retina and the intergeniculate leaflet of the lateral geniculate nucleus and are
      important in the entrainment of endogenous circadian rhythms. A characteristic
      feature of the suprachiasmatic nucleus and the intergeniculate leaflet of the
      thalamus is that they are bilaterally innervated from the retina. However, parts
      of the olivary and posterior pretectal nuclei have been shown to be bilaterally
      innervated from the retina as well. We therefore aimed to explore whether these
      two nuclei, in the rat, were anatomically related to the suprachiasmatic nucleus.
      The anterograde neuronal tract-tracer, Phaseolus vulgaris-leucoagglutinin, was
      injected iontophoretically into different pretectal nuclei. Pretectal injections
      centered only in the medial part of the pretectum, i.e. involving the olivary and
      posterior pretectal nuclei, gave rise to a substantial bilateral innervation of
      the suprachiasmatic nucleus. From the site of injection, Phaseolus vulgaris
      leucoagglutinin-immunoreactive nerve fibers coursed laterally and rostrally into
      the optic tract, and within the optic tract and chiasm, under the diencephalon to
      penetrate dorsally into the suprachiasmatic nucleus. Varicose Phaseolus vulgaris
      leucoagglutinin-labeled nerve fibers were found exclusively in the ventrolateral
      part of the suprachiasmatic nucleus, mostly on the ipsilateral side. To determine
      the precise location of the projecting neurons, the retrograde tracer Cholera
      toxin, subunit B, was iontophoretically injected into the suprachiasmatic
      nucleus. The presence of of labeled neurons scattered in both the posterior and
      olivary pretectal nuclei was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 7530344
TI  - Muscarinic cholinergic stimulation of the nitric oxide-cyclic GMP signaling
      system in cultured rat sensory neurons.
AB  - Acetylcholine or carbachol stimulated cyclic GMP production in neuronal cultures
      from embryonic rat dorsal root ganglia but not in non-neuronal dorsal root
      ganglia cultures. Acetylcholine stimulation of cyclic GMP production was mediated
      by muscarinic receptors and required extracellular Ca2+. Basal cyclic GMP
      production and acetylcholine-evoked cyclic GMP production were attenuated by
      Methylene Blue, suggesting the involvement of soluble guanylate cyclase and
      nitric oxide synthase. L-NG-Monomethyl arginine attenuated basal, acetylcholine
      or carbachol-stimulated cyclic GMP production; this inhibition of acetylcholine
      and carbachol stimulation of cyclic GMP was reversed by L-arginine. These results
      suggest that a nitrosyl factor mediates basal, as well as acetylcholine- and
      carbachol-stimulated, cyclic GMP production. Selective destruction of small
      diameter neurons by capsaicin pretreatment of dorsal root ganglion neuronal
      cultures abolished acetylcholine and capsaicin stimulation of cyclic GMP, but did
      not affect sodium nitroprusside stimulation of cyclic GMP. These results suggest
      that acetylcholine evoked production of a nitrosyl factor in capsaicin-sensitive
      (small diameter) sensory neurons, which subsequently stimulated a soluble
      guanylate cyclase and cyclic GMP production in adjacent neuronal and/or non
      neuronal cells. These results demonstrate that muscarinic agonists stimulate the
      nitric oxide-cyclic GMP signaling system in capsaicin-sensitive sensory neurons.
      Thus, the noxious character of acetylcholine when administered peripherally may
      be mediated by nitric oxide-cyclic GMP.

PMID- 7530346
TI  - Ipsilateral motor control of the forelimb in the congenitally acallosal mouse.
AB  - The corticospinal projections of mice with callosal agenesis were investigated
      using electro-physiological and horseradish peroxidase techniques. In the normal
      mouse, intracortical stimulation of the motor area with the microelectrode
      resulted in contralateral contraction of the forelimb, whereas ipsilateral
      contraction was observed in the acallosal mouse. Hence, mice with congenital
      absence of the corpus callosum show physiologically ipsilateral motor control.
      Furthermore, latency of the forelimb contraction elicited by electrical
      stimulation of the acallosal mouse was slightly shorter than that of the normal
      mouse. On the other hand, it was confirmed by a horseradish peroxidase technique
      that the corticospinal tract and peripheral motor neurons in the spinal cord of
      the acallosal mouse were identical to those of the normal mouse.

PMID- 7530347
TI  - Transganglionic transport and binding of the isolectin B4 from Griffonia
      simplicifolia I in rat primary sensory neurons.
AB  - The isolectin B4 from Griffonia simplicifolia I binds to a subpopulation of rat
      small-diameter dorsal root ganglion neurons, and to fibres and presumed terminals
      in laminae I-II of the spinal cord dorsal horn. In the present study we
      investigated B4 and B4 conjugated to horseradish peroxidase as potential
      transganglionic tracers of somatic primary afferent neurons after injection into
      a peripheral nerve. We also tried to identify the specific subpopulation of
      dorsal root ganglion neurons that bind and ganglion neurons that bind and
      transport B4. Following injection of B4 or B4-horseradish peroxidase into the
      sciatic nerve, labelled presumed terminals that reached peak labelling at two
      days were found exclusively in regions of the spinal cord gray matter known to
      receive unmyelinated primary afferent fibres. Almost all dorsal root ganglion
      cells that transported B4-horseradish peroxidase also bound B4. Cell counts
      showed that 51% of the dorsal root ganglion neurons were B4-positive and cell
      area measurements that these were all in the small size range. An extensive
      overlap was found between B4 and fluoride-resistant acid phosphatase (85%), and
      between B4 and calcitonin gene-related peptide (59%). Seventeen per cent of the
      B4-positive cells were substance P-immunoreactive and 9% were immunoreactive to
      somatostatin. Minimal overlap was seen between B4-positive cells and cells
      positive for RT97 (3%), a selective marker of primary afferent neurons with
      myelinated axons. All somatostatin-immunoreactive cells and almost all (95%) of
      the fluoride-resistant acid phosphatase-positive cells were contained within the
      B4-positive population. This comprised also 58% of the cells immunoreactive to
      calcitonin gene-related peptide and 42% of those immunoreactive to substance P.
      The results obtained show that B4 binds to a subpopulation of unmyelinated
      primary afferent neurons, and that B4 and B4-horseradish peroxidase can be used
      as selective transganglionic tracers of this specific cell subpopulation.

PMID- 7530349
TI  - Melatonin deacetylase activity in the pineal gland and brain of the lizards
      Anolis carolinensis and Sceloporus jarrovi.
AB  - Melatonin modulates a variety of rhythmic processes in vertebrates, and is
      synthesized in both the retina and pineal gland. We have shown previously that
      retinal melatonin is deacetylated generating 5-methoxytryptamine, which is then
      deaminated by monoamine oxidase, producing 5-methoxyindoleacetic acid and 5
      methoxytryptophol. This process occurs within the eyes of a variety of
      vertebrates including the iguanid lizard Anolis carolinensis. To determine
      whether melatonin deacetylase activity also occurs in the pineal organ or in
      other parts of the lizard brain, pineals and brains of Anolis carolinensis and
      Sceloporus jarrovi were cultured in the presence of [3H-methoxy]-melatonin. High
      performance liquid chromatography of the resulting culture media and tissues
      revealed the generation of radiolabeled 5-methoxytryptamine and 5
      methoxyindoleacetic acid. These two methoxyindoles were the only radiolabeled
      metabolites detectable, and together accounted for all melatonin lost. Both the
      loss of melatonin and the production of melatonin metabolites were inhibited by
      inclusion of 100 microM eserine, an inhibitor of the melatonin deacetylase.
      Pargyline, a monoamine oxidase inhibitor, reduced the production of 5
      methoxyindoleacetic acid and increased the production of 5-methoxytryptamine
      relative to control incubations. Similar effects of eserine and pargyline were
      seen in eyecup, brain and pineal gland, but the specific activity of melatonin
      deacetylation in cultured pineal glands was much greater than in either brains or
      eyecups. These results indicate that pineal glands of both Anolis carolinensis
      and Sceloporus jarrovi can rapidly catabolize melatonin by a mechanism very
      similar to that in the eye, that the melatonin deacetylation pathway exists
      elsewhere in the iguanid brain, and also extend our previous observations of
      ocular melatonin deacetylation to an additional species.

PMID- 7530348
TI  - The immunophilins, FK506 binding protein and cyclophilin, are discretely
      localized in the brain: relationship to calcineurin.
AB  - The immunosuppressant drugs cyclosporin A and FK506 bind to small, predominantly
      soluble proteins cyclophilin and FK506 binding protein, respectively, to mediate
      their pharmacological actions. The immunosuppressant actions of these drugs occur
      through binding of cyclophilin-cyclosporin A and FK506 binding protein-FK506
      complexes to the calcium-calmodulin-dependent protein phosphatase, calcineurin,
      inhibiting phosphatase activity. Utilizing immunohistochemistry, in situ
      hybridization and autoradiography, we have localized protein and messenger RNA
      for FK506 binding protein, cyclophilin and calcineurin. All three proteins and/or
      messages exhibit a heterogenous distribution through the brain and spinal cord,
      with the majority of the localizations being neuronal. We observe a striking co
      localization of FK506 binding protein and calcineurin in most brain regions and a
      close similarity between calcineurin and cyclophilin. FK506 binding protein and
      cyclophilin localizations largely correspond to those of calcineurin, although
      cyclophilin is enriched in some brain areas that lack calcineurin. The dramatic
      similarities in localization of FK506 binding proteins and cyclophilins with
      calcineurin suggest related functions.

PMID- 7530350
TI  - Pressor responses to electrical and chemical stimulation of the rat brain A10
      dopaminergic system.
AB  - Central dopaminergic systems have been implicated in the regulation of blood
      pressure. We examined the effect on blood pressure of electrical or chemical
      stimulation of the rat brain ventral tegmental area (VTA) which is the region of
      origin of the A10 dopaminergic system. Electrical stimulation in urethane
      anaesthetised rats (10-120 Hz, 80 microA) produced frequency-dependent increases
      in blood pressure (max 30-35 mmHg). These pressor responses could be
      significantly attenuated by pretreatment with the dopamine D2 receptor antagonist
      haloperidol, but not the D1 receptor antagonist SCH 23390. Chemical stimulation
      of the VTA, by microinjection of 10 nmol of the substance P analogue DiMe-C7,
      produced a sustained increase in blood pressure (max 10-15 mmHg), which could be
      completely prevented by pretreatment with haloperidol. These results suggest that
      stimulation of dopaminergic neurons in the VTA induces pressor responses and that
      projections from midbrain dopaminergic neurons, acting on dopamine D2 receptors,
      play a role in the regulation of blood pressure.

PMID- 7530351
TI  - SP- and CGRP-immunoreactive axons differ in their ability to reinnervate the skin
      of the rat tail.
AB  - The reinnervation of cutaneous targets was studied in the rat tail after proximal
      lesions of all collector nerves. The distribution of immunofluorescent nerve
      fibres stained for calcitonin-gene-related peptide (CGRP) and substance P (SP)
      was examined after 110-210 days. Targets at all sites were reinnervated by CGRP
      immunoreactive (IR) fibres. However, SP-IR terminals were rare, particularly
      distally, despite staining within subdermal nerve trunks.

PMID- 7530352
TI  - A novel in vivo assay system for consecutive measurement of brain nitric oxide
      production combined with the microdialysis technique.
AB  - A novel spectrophotometric nitrite (NO2-)/nitrate (NO3-) assay system for a small
      quantity (5 microliter) of dialysate sample obtained by in vivo brain
      microdialysis was developed based on the diazotization reaction. The system has
      the advantage of in vivo consecutive measurement, high precision, good
      reproducibility, technical simplicity, relatively short resolution time (2.5-20
      min), and wide availability. The NO3- level in the rat striatum was found to be 3
      times higher than the NO2- level. A nitric oxide (NO) synthase inhibitor, NG
      nitro-L-arginine methyl ester, reduced striatal NO2-/citrulline formation in a
      dose-related manner and increased arginine, indicating that the tissue NO2- level
      detected by this assay system adequately reflects the striatal NO synthase
      activity.

PMID- 7530353
TI  - Selective blockade of the hyperpolarization-activated cationic current (Ih) in
      guinea pig substantia nigra pars compacta neurones by a novel bradycardic agent,
      Zeneca ZM 227189.
AB  - The effects of a novel bradycardic agent Zeneca ZM 227189 (4-(N-ethyl-N
      phenylamino)-1,2-dimethyl-6-(methylamino) triazinium iodide) were tested on the
      inward rectifying properties of guinea-pig substantia nigra pas compacta (SNC)
      and guinea-pig olfactory cortical cells recorded in vitro. In SNC neurones, ZM
      227189 (10-100 microM) produced a dose-dependent block of the slow anomalous
      rectifier; under voltage clamp, a clear reduction was seen in the amplitude of
      the slow inward current (Ih) relaxation evoked by negative voltage commands from
      a holding potential of -60 mV. ZM 227189 (50-100 microM) induced an irreversible
      block of the Ih current after 10-15 min exposure. A similar block of Ih was
      observed following application of 5 mM Cs+. ZM 227189 had little effect on other
      membrane properties. By contrast, in olfactory cortical neurones, ZM 227189 (100
      microM) induced an increase in the input resistance (approximately 20%) and cell
      excitability, accompanied by a small (< 2 mV) hyperpolarization; these effects
      were also not reversible. Activation of the fast (K(+)-mediated) inward rectifier
      at negative membrane potentials remained unaffected. Lower concentrations (1-10
      microM) of ZM 227189 had no obvious effect on cortical cell properties. Our data
      indicate that ZM 227189 is a potent and apparently selective blocker of Ih in
      substantia nigra neurones, but has no effect on the fast-type inward rectifier in
      olfactory cortical cells.